PMID- 27020618
TI  - Advantages and disadvantages of breath alcohol analysis-Reply to "Evidential
      breath alcohol analysis and the venous blood-to-breath ratio".

PMID- 27020619
TI  - Suicide by self-injection of chlormequat trademark C5SUN((r)).
AB  - Chlormequat is a quaternary ammonium used as plant growth regulating agent. We
      report here the first suicide case involving a 45 year-old farmer man who
      intentionally self-injected C5SUN((r)), containing chlormequat and choline. An
      original liquid chromatography high resolution mass spectrometry method (LC-HR
      MS), using a hybrid quadrupole-orbitrap mass spectrometer, was developed for
      qualitative and quantitative analysis of chlormequat in different biological
      matrices. Toxicological analyses of post-mortem samples highlighted the presence
      of chlormequat in the blood (2.25mg/L) and the urine (4.45mg/L), in addition to
      ethanol impregnation blood (1.15g/L). The route of administration (subcutaneous
      injection) was confirmed by the detection of chlormequat in the abdominal fat
      sample (chlormequat: 10.04mg/g) taken from the traumatic injury location, as well
      as in the syringe found at the death scene, close to the victim's body. Based on
      the results of these post-mortem investigations, the cause of death was
      determined to be consecutive to cardiac dysrhythmia and cardiac arrest following
      chlormequat self-injection. 

PMID- 27020620
TI  - Ten-year outcomes using low dose rate brachytherapy for localised prostate
      cancer: An update to the first Australian experience.
AB  - INTRODUCTION: To report long-term prostate-specific antigen (PSA) and toxicity
      outcomes for patients with localised prostate cancer treated with Iodine-125
      permanent implantation at a single Australian centre. METHODS: Between September
      1994 and November 2007, 207 patients at Sir Charles Gairdner Hospital with
      localised prostate cancer were consecutively treated with Iodine-125 permanent
      interstitial implantation. Post-therapy assessment was performed three times a
      month and included clinical review and biochemical (PSA) evaluation. PSA
      progression was evaluated using the Phoenix (nadir + 2.0) definition. Treatment
      related morbidity was assessed using the Common Terminology Criteria for Adverse
      Events (CTCAE) version 3.0 guidelines. The rate of biochemical failure was
      calculated by Kaplan-Meier plots. Univariate and multivariate analyses were
      performed to evaluate outcomes by pre-treatment clinical prognostic factors and
      radiation dosimetry. RESULTS: Median follow-up was 7.8 years. The 10-year
      biochemical disease-free survival (bDFS) for the entire cohort was 89%. Ten-year
      bDFS estimates by pre-treatment risk group were 96% for low-risk, 83% for
      intermediate-risk and 50% for high-risk disease. On multivariate analysis, pre
      treatment PSA was an independent predictor of bDFS. D90 dose did not show a
      statistically significant effect on bDFS. The peak incidences of late grade 3 or
      higher urinary and rectal toxicities were 10.7% and 1.1% respectively.
      CONCLUSION: Excellent long-term biochemical control was demonstrated with Iodine
      125 permanent interstitial implantation in appropriately selected patients with
      prostate cancer. The results of our single centre experience are comparable with
      those of other single institutions.

PMID- 27020621
TI  - One-Pot Two-Step Multicomponent Process of Indole and Other Nitrogenous
      Heterocycles or Amines toward alpha-Oxo-acetamidines.
AB  - A cesium carbonate promoted three-component reaction of N-H containing
      heterocycles, primary or secondary amines, arylglyoxaldehydes, and anilines is
      reported. The key step involves a tandem sequence of N-1 addition of a
      heterocycle or an amine to preformed alpha-iminoketones, followed by an air- or
      oxygen-mediated oxidation to form alpha-oxo-acetamidines. The scope of the
      reaction is enticingly broad, and this novel methodology is applied toward the
      synthesis of various polycyclic heterocycles. 

PMID- 27020622
TI  - Signs and symptoms associated with digestive tract development.
AB  - OBJECTIVE: To analyze the development and prevalence of gastrointestinal signs
      and symptoms associated with the development of the digestive tract, and to
      assess the measures aimed to reduce their negative impacts. SOURCE OF DATA:
      Considering the scope and comprehensiveness of the subject, a systematic review
      of the literature was not carried out. The Medline database was used to identify
      references that would allow the analysis of the study topics. SYNTHESIS OF
      RESULTS: Infants frequently show several gastrointestinal signs and symptoms.
      These clinical manifestations can be part of gastrointestinal functional
      disorders such as infantile colic, infant regurgitation, and functional
      constipation. Allergy to cow's milk protein and gastroesophageal reflux disease
      are also causes of these clinical manifestations and represent an important and
      difficult differential diagnosis. The diseases that course with gastrointestinal
      signs and symptoms can have an impact on family dynamics and maternal emotional
      status, and may be associated with future problems in the child's life.
      Comprehensive pediatric care is essential for diagnosis and treatment. Maternal
      breastfeeding should always be maintained. Some special formulas can contribute
      to the control of clinical manifestations depending on the established diagnosis.
      CONCLUSION: During the normal development of the digestive tract, several
      gastrointestinal signs and symptoms may occur, usually resulting from functional
      gastrointestinal disorders, gastroesophageal reflux disease, and allergy to cow's
      milk protein. Breastfeeding should always be maintained.

PMID- 27020623
TI  - Morphology and Aquaporin Immunohistochemistry of the Uterine Tube of Saanen Goats
      (Capra hircus): Comparison Throughout the Reproductive Cycle.
AB  - The expression of six different aquaporins (AQP1, 2, 3, 4, 5 and 9), integral
      membrane water channels that facilitate bi-directional passive movement of water,
      was investigated by immunohistochemistry in the uterine tube of pre-pubertal and
      adult Saanen goats (Capra hircus), comparing the different phases of the oestrous
      cycle. Regional morphology and secretory processes were markedly different during
      the goat oestrous cycle. The tested AQP molecules showed different expression
      patterns in comparison with already studied species. AQP1-immunoreactivity was
      evidenced at the endothelium of blood vessels and in nerve fibres, regardless of
      the tubal tract and cycle period. AQP4-immunoreactivity was shown on the lateral
      plasmalemma in the basal third of the epithelial cells at infundibulum and
      ampulla level in the cycling goats, more evidently during follicular than during
      luteal phase. No AQP4-immunoreactivity was noticed at the level of the isthmus
      region, regardless of the cycle phase. AQP5-immunoreactivity, localized at the
      apical surface of epithelial cells, increased from pre-puberty to adulthood.
      Thereafter, AQP5-immunoreactivity was prominent during the follicular phase, when
      it strongly decorated the apical plasmalemma of all epithelial cells at ampullary
      level. During luteal phase, immunoreactivity was discontinuous, being weak to
      strong at the apex of the secretory cells protruding into the lumen. In the
      isthmus region, the strongest AQP5-immunoreactivity was seen during follicular
      phase, with a clear localization in the apical plasmalemma of all the epithelial
      cells and also on the lateral plasmalemma. AQP2, 3 and 9 were undetectable all
      along the goat uterine tube. Likely, a collaboration of different AQP molecules
      sustains the fluid production in the goat uterine tube. AQP1-mediated
      transudation from the blood capillaries, together with permeation of the
      epithelium by AQP4 in the basal rim of the epithelial cells and final intervening
      of apical AQP5, could be involved in fluid production as well as in secretory
      processes. 

PMID- 27020624
TI  - The Magnum Opus: Near-peer teaching combined with questions banks.

PMID- 27020625
TI  - Editorial overview: Theory and simulation.

PMID- 27020626
TI  - Pathologic response to preoperative transarterial chemoembolization for
      resectable hepatocellular carcinoma may not predict recurrence after liver
      resection.

PMID- 27020627
TI  - Older age at first birth is a risk factor for pancreatic cancer: a meta-analysis.
AB  - BACKGROUND: Some studies found that age at first birth is associated with
      pancreatic cancer; others did not. The present meta-analysis was to evaluate the
      relationship between age at first birth and pancreatic cancer in women. DATA
      SOURCES: We searched PubMed, Embase, and the Cochrane Library for relevant
      publications on age at first birth and pancreatic cancer up to April, 2014. The
      eligible studies (six cohorts and five case-controls) were independently selected
      by two authors. Pooled relative risk (RR) estimates and corresponding 95%
      confidence interval (95% CI) were calculated using the inverse-variance method.
      RESULTS: The pooled RR of pancreatic cancer risk for the highest versus lowest
      categories of age at first birth was 1.21 (95% CI: 1.01-1.45, P=0.314, I2=13.7%).
      Consistent relationships were also observed within subgroup analyses stratified
      by study design, geographic region, and whether the studies included adjustment
      for cigarette smoking, diabetes, or all of the confounders. In this meta
      analysis, no publication bias among studies was observed using Egger's test
      (P=0.383) or Begg's test (P=0.436). CONCLUSION: Our findings suggest that older
      age at first birth is associated with an increased risk of pancreatic cancer in
      women and the exact functional mechanism needs further investigation.

PMID- 27020628
TI  - Hyaluronic acid algorithm-based models for assessment of liver fibrosis:
      translation from basic science to clinical application.
AB  - BACKGROUND: The estimation of liver fibrosis is usually dependent on liver biopsy
      evaluation. Because of its disadvantages and side effects, researchers try to
      find non-invasive methods for the assessment of liver injuries. Hyaluronic acid
      has been proposed as an index for scoring the severity of fibrosis, alone or in
      algorithm models. The algorithm model in which hyaluronic acid was used as a
      major constituent was more reliable and accurate in diagnosis than hyaluronic
      acid alone. This review described various hyaluronic acid algorithm-based models
      for assessing liver fibrosis. DATA SOURCE: A PubMed database search was performed
      to identify the articles relevant to hyaluronic acid algorithm-based models for
      estimating liver fibrosis. RESULT: The use of hyaluronic acid in an algorithm
      model is an extra and valuable tool for assessing liver fibrosis. CONCLUSIONS:
      Although hyaluronic acid algorithm-based models have good diagnostic power in
      liver fibrosis assessment, they cannot render the need for liver biopsy obsolete
      and it is better to use them in parallel with liver biopsy. They can be used when
      frequent liver biopsy is not possible in situations such as highlighting the
      efficacy of treatment protocol for liver fibrosis.

PMID- 27020629
TI  - Role of microRNA in liver regeneration.
AB  - BACKGROUND: Liver regeneration is a complex process. microRNAs (miRNAs) are
      short, single-stranded RNAs that modify gene expression at the post
      transcriptional level. Recent investigations have revealed that miRNAs are
      closely linked to liver regeneration. DATA SOURCES: All included studies were
      obtained from PubMed, Embase, the ScienceDirect databases and Web of Science,
      with no limitation on publication year. Only studies published in English were
      considered. RESULTS: We grouped studies that involved miRNA and liver
      regeneration into two groups: miRNAs as promoters and as inhibitors of liver
      regeneration. We summarized the relevant miRNAs separately from the related
      pathways. CONCLUSIONS: Blocking or stimulating the pathways of miRNAs in liver
      regeneration may be novel therapeutic strategies in future regeneration-related
      liver managements. We may discover additional chemotherapy targets of miRNA.

PMID- 27020630
TI  - Liver transplantation for hepatocellular carcinoma: is zero recurrence
      theoretically possible?
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) recurrence remains a key issue after
      liver transplantation. This study aimed to determine a subgroup of HCC patients
      within the Milan criteria who could achieve a theoretical goal of zero recurrence
      rates after liver transplantation. METHODS: Between 1999 and 2009, 179 patients
      who received liver transplantation for HCC within the Milan criteria were
      retrospectively included. Analysis of the factors associated with HCC recurrence
      was performed to determine the subgroup of patients at the lowest risk of
      recurrence. RESULTS: Seventy-two percent of the patients received a bridging
      therapy, including 54 liver resections. Eleven (6.1%) patients recurred within a
      delay of 19+/-22 months and ultimately died. Factors associated with recurrence
      were serum alpha-fetoprotein level >400 ng/mL, satellite nodules, poor
      differentiation, microvascular invasion and cholangiocarcinoma component.
      Recurrence rates decreased from 6.1% to 3.1% in patients without any of these
      factors. CONCLUSIONS: Among HCC patients within the Milan criteria, selecting
      patients with factors based on histology would allow tending towards zero
      recurrence, and prior histological assessment by liver biopsy or resection may be
      essential to rule out poorly differentiated tumors, microvascular invasion, and
      cholangiocarcinoma component.

PMID- 27020631
TI  - Cancer of the Liver Italian Program score helps identify potential candidates for
      transarterial chemoembolization in patients with Barcelona Clinic Liver Cancer
      stage C.
AB  - BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system for
      hepatocellular carcinoma (HCC) recommends transarterial chemoembolization (TACE)
      as the first line therapy for stage B patients and sorafenib treatment for stage
      C patients. However, stage C patients exhibit variations in terms of tumor
      burden, liver function, and extrahepatic metastasis, which could potentially
      affect disease outcome. Here, we assessed whether the Cancer of the Liver Italian
      Program (CLIP) scores can help identify stage C patients likely to benefit from
      TACE. METHODS: Out of 295 BCLC stage C HCC patients enrolled between January 2009
      and December 2011, those with platelet counts >30 X 10(9) cells/L, total
      bilirubin <51 MUmoL/L, and an unobstructed main portal vein were scheduled for
      TACE (n=195). The remaining patients received best supportive care (BSC, n=100).
      All the patients were followed up for symptoms, performance status, and Child
      Pugh classification scores every 4 weeks until death or December 2013. The
      prognosis of each group was evaluated by using the log-rank test and Cox-Mantel
      test. RESULTS: The median overall survival (OS) was 6 months [95% confidence
      interval (CI): 4.64-7.36]. The OS was 9 months for the TACE group and 4 months
      for the BSC group. The TACE group had a longer OS than the BSC subgroup for CLIP
      scores 0-2 [13 months (95% CI: 8.55-17.45) vs 4 months (95% CI: 0.00-10.96),
      P=0.001]. No significant differences were found between the TACE and BSC groups
      for CLIP scores 3-5. The CLIP score and treatment methods were found to be
      independent prognostic factors. CONCLUSIONS: BCLC stage C HCC patients exhibit
      definite disease heterogeneity and can be reclassified by using the CLIP scoring
      system. Moreover, patients with CLIP scores 0-2 are likely to benefit from TACE.
      However, additional studies with long-term follow-up will be required to validate
      these findings.

PMID- 27020632
TI  - Pathologic response to preoperative transarterial chemoembolization for
      resectable hepatocellular carcinoma may not predict recurrence after liver
      resection.
AB  - BACKGROUND: Pathologic response (PR) predicts survival after preoperative
      chemotherapy and resection of a malignancy. Occasionally, transarterial
      chemoembolization (TACE) may be selected for preoperative management of
      resectable hepatocellular carcinoma (HCC). This study investigated whether PR to
      preoperative TACE can predict recurrence after resection for resectable HCC.
      METHODS: We conducted analysis of 106 HCC patients who underwent TACE followed by
      liver resection with a curative intent. The PR was evaluated as the mean
      percentage of non-viable tumor area within each tumor. We divided the patients
      into three groups according to response rate: complete PR (CPR), major response
      (MJR: PR>=50%) and minor response (MNR: PR<50%). The primary endpoint was disease
      free survival, and the secondary endpoints were predicting factors for tumor
      recurrence and MJR+CPR. RESULTS: Among the 121 TACE patients, PR could be
      measured in 106 (87.6%). The mean interval between TACE and liver resection was
      33.1 days. The 5-year disease-free survival rates by PR status were as follows:
      40.6% CPR, 43.7% MJR, and 49.0% MNR (P=0.815). There were also no significant
      differences in overall survival between the three groups. Multivariate analyses
      revealed that microvascular invasion and capsular invasion (hazard ratio
      [HR]=11.224, P=0.002 and HR=2.220, P=0.043) were independent predictors of
      disease-free survival. Multivariate analysis of the predictors of above 50% PR
      revealed that only hepatitis B was an independent factor. CONCLUSION: These data
      could reflect that the PR after TACE for resectable HCC may not be useful for
      predicting recurrence of HCC after resection.

PMID- 27020633
TI  - Beneficial effect of refined red palm oil on lipid peroxidation and monocyte
      tissue factor in HCV-related liver disease: a randomized controlled study.
AB  - BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous
      blood of patients with liver cirrhosis, contributing to the pathogenesis of
      hepatotoxicity because of its role in oxidative stress. The present study aimed
      to test the effect of the supplementation with red palm oil (RPO), which is a
      natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat
      soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and
      endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory
      cytokines profile, and monocyte tissue factor in patients with chronic liver
      disease. METHODS: The study group consisted of sixty patients (34 males and 26
      females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related
      cirrhosis without a history of ethanol consumption, randomly enrolled into an 8
      week oral daily treatment with either vitamin E or RPO. All patients had
      undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them
      showed esophageal varices. RESULTS: Both treatments significantly decreased
      erythrocyte malondialdehyde and urinary isoprostane output, only RPO
      significantly affected macrophage-colony stimulating factor and monocyte tissue
      factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO
      beneficially modulates oxidative stress and, not least, downregulates
      macrophage/monocyte inflammatory parameters. RPO can be safely advised as a
      valuable nutritional implementation tool in the management of chronic liver
      diseases.

PMID- 27020634
TI  - Efficient generation of functional hepatocyte-like cells from mouse liver
      progenitor cells via indirect co-culture with immortalized human hepatic stellate
      cells.
AB  - BACKGROUND: Differentiation of liver progenitor cells (LPCs) to functional
      hepatocytes holds great potential to develop new strategies for hepatocyte
      transplantation and the screening of drug-induced cytotoxicity. However, reports
      on the efficient and convenient hepatic differentiation of LPCs to hepatocytes
      are few. The present study aims to investigate the possibility of generating
      functional hepatocytes from LPCs in an indirect co-culture system. METHODS: Mouse
      LPCs were co-cultured in Transwell plates with an immortalized human hepatic
      stellate cell line (HSC-Li) we previously established. The morphology, expression
      of hepatic markers, and functions of mouse LPC-derived cells were monitored and
      compared with those of conventionally cultured LPCs. RESULTS: Co-culturing with
      HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte
      like cells. The differentiated cells were morphologically transformed into
      hepatocyte-like cells 3 days after co-culture initiation. In addition, the
      differentiated cells expressed liver-specific genes and possessed hepatic
      functions, including glycogen storage, low-density lipoprotein uptake, albumin
      secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity.
      CONCLUSIONS: Our method, which employs indirect co-culture with HSC-Li cells, can
      efficiently induce the differentiation of LPCs into functional hepatocytes. This
      finding suggests that this co-culture system can be a useful method for the
      efficient generation of functional hepatocytes from LPCs.

PMID- 27020635
TI  - Individualized nomogram improves diagnostic accuracy of stage I-II gallbladder
      cancer in chronic cholecystitis patients with gallbladder wall thickening.
AB  - BACKGROUND: Early diagnosis of gallbladder cancer (GBC) can remarkably improve
      the prognosis of patients. This study aimed to develop a nomogram for
      individualized diagnosis of stage I-II GBC in chronic cholecystitis patients with
      gallbladder wall thickening. METHODS: The nomogram was developed using logistic
      regression analyses based on a retrospective cohort consisting of 89 consecutive
      patients with stage I-II GBC and 1240 patients with gallbladder wall thickening
      treated at one biliary surgery center in Shanghai between January 2009 and
      December 2011. The accuracy of the nomogram was validated by discrimination,
      calibration and a prospective cohort treated at another center between January
      2012 and December 2014 (n=928). RESULTS: Factors included in the nomogram were
      advanced age, hazardous alcohol consumption, long-standing diagnosed gallstones,
      atrophic gallbladder, gallbladder wall calcification, intraluminal polypoid
      lesion, higher wall thickness ratio and mucosal line disruption. The nomogram had
      concordance indices of 0.889 and 0.856 for the two cohorts, respectively.
      Internal and external calibration curves fitted well. The area under the receiver
      operating characteristic curves of the nomogram was higher than that of
      multidetector row computed tomography in diagnosis of stage I-II GBC (P<0.001).
      CONCLUSION: The proposed nomogram improves individualized diagnosis of stage I-II
      GBC in chronic cholecystitis patients with gallbladder wall thickening,
      especially for those the imaging features alone do not allow to confirm the
      diagnosis.

PMID- 27020636
TI  - Analysis of 300 consecutive cases of pancreatic adenocarcinoma in a single-center
      in China.
AB  - BACKGROUND: Most of the reports on the prognostic indicators of patients with
      pancreatic adenocarcinoma are from developed countries. The present study focused
      on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma.
      METHODS: A total of 300 patients with pancreatic adenocarcinoma who had undergone
      curative resection were included. The resection and R0/R1 resection rates for
      adenocarcinomas from different parts of the pancreas were calculated and clinical
      characteristics were analyzed. RESULTS: In 3427 patients diagnosed with
      pancreatic adenocarcinomas, only 300 (8.8%) were eligible for radical resection.
      The total median survival of these patients was 19 months, and their 1-, 3-, and
      5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic
      factors included socioeconomic status, smoking history, symptoms, high blood
      glucose, and various tumor characteristics, including perineural and vascular
      invasion, lymph node metastases, and CA19-9 levels before and after operation.
      Operation-associated prognostic indicators included operation time, blood loss
      and transfusions, pancreatic fistula, and complications. Independent predictors
      of mortality included poor socioeconomic status, smoking history, symptoms, CA19
      9, perineural invasion and lymph node metastasis, grade of fistula and
      complications. Patient survival was not correlated with either resection margin
      or adjuvant chemotherapy in multivariate analysis. CONCLUSIONS: The survival
      rates of patients with curative resection for pancreatic adenocarcinoma in China
      are close to those in developed countries, but curative resection rate is far
      below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent
      prognostic factors, which are helpful in patient selection and perioperative
      care.

PMID- 27020637
TI  - Improvement of gastric emptying by enhanced recovery after
      pancreaticoduodenectomy.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) has improved postoperative
      outcomes particularly in colorectal surgery. This study aimed to assess
      compliance with an ERAS protocol and evaluate its effect on postoperative
      outcomes in patients undergoing pancreaticoduodenectomy. METHODS: Fifty patients
      who had received conventional perioperative management from 2005 to 2009
      (conventional group) were compared with 75 patients who had received
      perioperative care with an ERAS protocol (fast-track group) from 2010 to 2014.
      Mortality, complications, readmissions and length of hospital stay were evaluated
      and compared in the groups. RESULTS: Compliance with each element of the ERAS
      protocol ranged from 74.7% to 100%. Uneventful patients had a significant higher
      adherence to the ERAS protocol (87.5% vs 40.7%; P<0.001). There were no
      significant differences in demographics and perioperative characteristics between
      the two groups. Patients in the fast-track group had a shorter time to remove the
      nasogastric tube, start liquid diet and solid food, pass flatus and stools, and
      remove drains. No difference was found in mortality, relaparotomy, readmission
      rates and overall morbidity. However, delayed gastric emptying and length of
      hospital stay were significantly reduced in the fast-track group. The independent
      effect of the ERAS protocol in reducing delayed gastric emptying and length of
      hospital stay was confirmed by multivariate analysis. CONCLUSION: ERAS pathway
      was feasible and safe in improving gastric emptying, yielding an earlier
      postoperative recovery, and reducing the length of hospital stay.

PMID- 27020638
TI  - Monocyte chemoattractant protein-1, transforming growth factor-beta1, nerve
      growth factor, resistin and hyaluronic acid as serum markers: comparison between
      recurrent acute and chronic pancreatitis.
AB  - BACKGROUND: Diagnostic parameters that can predict the presence of chronic
      pancreatitis (CP) in patients with recurrent pain due to pancreatitis would help
      to direct appropriate therapy. This study aimed to compare the serum levels of
      monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta1 (TGF
      beta1), nerve growth factor (NGF), resistin and hyaluronic acid (HA) in patients
      with recurrent acute pancreatitis (RAP) and CP to assess their ability to
      differentiate the two conditions. METHODS: Levels of serum markers assessed by
      enzyme-linked immunosorbent assay (ELISA) were prospectively compared in
      consecutive patients with RAP, CP and in controls, and stepwise discriminant
      analysis was performed to identify the markers differentiating RAP from CP.
      RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78
      healthy controls were prospectively enrolled. The mean (SD) age of the patients
      was 32.0 (14.0) years; 89 (78.8%) were male. All markers were significantly
      higher in CP patients than in the controls (P<0.001); MCP-1, NGF and HA were
      significantly higher in RAP patients than in the controls (P<0.001). Stepwise
      discriminant analysis showed significant difference (P=0.002) between RAP and CP
      for resistin with an accuracy of 61.9%, discriminant scores of <=-0.479 and
      >=0.189 indicating RAP and CP, respectively. The other markers had no
      differential value between RAP and CP. CONCLUSION: Serum resistin is a promising
      marker to differentiate between RAP and CP and needs validation in future
      studies, especially in those with early CP.

PMID- 27020639
TI  - Surgical treatment of synchronous colorectal liver and lung metastases: the
      usefulness of thoracophrenolaparotomy for single stage resection.
AB  - When suitable, surgery still remains the therapeutic option to be preferred for
      patients carrier of colorectal liver and lung metastases. Since
      thoracophrenolaparotomy should be helpful during liver resection for some of
      these patients, simultaneous removal of right lung metastases can be proposed
      through this approach. Eleven consecutive patients (median age of 53 years)
      carrier of colorectal liver and lung metastases, underwent single session
      surgical resection of both liver and right lung lesions by means of J-shaped
      thoracophrenolaparotomy. The median number of liver metastases removed was 5
      (range 2-30) and of lung metastases removed was 2 (range 1-3). Lung metastases
      were located in the upper lobe in 1 patient, in the middle lobe in 2, in the
      lower lobe in 6, and in the upper and lower lobe in 2. Mortality and major
      morbidity were nil. Two patients had a minor morbidity: one had wound infection
      and bile leakage treated conservatively and the other had transient fever. Mean
      overall survival was 24.4 months. An aggressive surgical approach should be
      undertaken for colorectal metastases: in case of multifocal liver disease with
      complex presentations, J-shaped thoracophrenolaparotomy could be considered as
      safe approach for combined liver and right lung metastasectomies. 

PMID- 27020641
TI  - PSA 2011 Abstracts.

PMID- 27020640
TI  - An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography
      jaundice.
AB  - Despite the effectiveness of endoscopic retrograde cholangiopancreatography
      (ERCP) for the treatment of choledocholithiasis, various complications have been
      described. We herein report the first case of prolonged post-ERCP jaundice due to
      toxicity of the contrast agent Iobitridol ((r)XENETIX, Guerbet, Roissy CdG Cedex,
      France) in a patient who underwent ERCP with sphincterectomy and common bile duct
      stone removal. While clinical improvement and normalization of aminotransferases
      and cholestatic enzymes after the procedure, an unexplained increase of direct
      bilirubin was noticed. A second ERCP was performed one week later, excluding
      possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin
      increased further up to 15 mg/dL. Other potential causes of direct
      hyperbilirubinemia were ruled out and patient's liver biopsy was compatible with
      drug-induced liver toxicity. Additionally, the cause-result time connection
      between the use of Iobitridol and bilirubin increase indicated the possibility of
      a toxic effect related to the repeated use of the particular contrast agent.
      Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia. 

PMID- 27020642
TI  - Assessment of health-related quality of life of patients with inflammatory bowel
      diseases in Eastern Province, Saudi Arabia.
AB  - Inflammatory bowel disease patients have impaired quality of life with physical,
      social and emotional dysfunction. This project aimed to assess the effects of
      socio-demographic and clinical variables on quality of life and to identify its
      predictors. In a cross-sectional paper-based study, 50 consecutive non-selected
      patients attending the teaching hospital completed a disease-specific McMaster
      quality of life tool. Socio-demographic and clinical data were collected from
      patients' records. The t-test and Mann-Whitney test were used to determine the
      probability of significant differences between quality of life domains and
      independent variables. Multiple linear regression was used to determine quality
      of life predictors. Younger and highly educated patients had higher social
      scores. Those with shorter disease durations had higher systemic scores. Patients
      in remission had higher systemic, social, bowel and overall scores. Relapse was a
      significant predictor of decreased systemic, social, bowel and overall scores.
      Long disease duration was a significant predictor of decreased systemic and
      overall scores. Younger age at disease onset was a significant predictor of
      decreased emotional score. However, high education was a significant predictor of
      improved social score. Relapse, long disease duration, low education and young
      age at disease onset were associated with low quality of life. Prospective
      studies should investigate how interventions addressing these predictors may lead
      to improved quality of life.

PMID- 27020643
TI  - Meeting Report: 2015 PDA Virus & TSE Safety Forum.
AB  - The report provides a summary of the presentations at the Virus & TSE Safety
      Forum 2015 organized by the Parenteral Drug Association (PDA) and held in
      Cascais, Portugal, from 9 to 11 June, 2015. As with previous conferences of this
      series, the PDA Virus & TSE Safety Forum 2015 provided an excellent forum for the
      exchange of information and opinions between the industry, research
      organizations, and regulatory bodies. Regulatory updates on virus and TSE safety
      aspects illustrating current topics of discussion at regulatory agencies in
      Europe and the United States were provided; the conference covered emerging
      viruses and new virus detection systems that may be used for the investigation of
      human pathogenic viruses as well as the virus safety of cell substrates and of
      raw material of ovine/caprine or human origin. Progress of development and use of
      next-generation sequencing methods was shown by several examples. Virus clearance
      data illustrating the effectiveness of inactivation or removal methods were
      presented and data provided giving insight into the mechanism of action of these
      technologies. In the transmissible spongiform encephalopathy (TSE) part of the
      conference, the epidemiology of variant Creutzfeldt-Jakob disease was reviewed
      and an overview about diagnostic tests provided; current thinking about the
      spread and propagation of prions was presented and the inactivation of prions by
      disinfection (equipment) and in production of bovine-derived reagents (heparin)
      shown. The current report provides an overview about the outcomes of the 2015 PDA
      Virus & TSE Safety Forum, a unique event in this field. 

PMID- 27020644
TI  - A Roadmap for the Implementation of Continued Process Verification.
AB  - In 2014, the members of the BioPhorum Operations Group (BPOG) produced a 100-page
      continued process verification case study, entitled "Continued Process
      Verification: An Industry Position Paper with Example Protocol". This case study
      captures the thought processes involved in creating a continued process
      verification plan for a new product in response to the U.S. Food and Drug
      Administration's guidance on the subject introduced in 2011. In so doing, it
      provided the specific example of a plan developed for a new molecular antibody
      product based on the "A MAb Case Study" that preceded it in 2009.This document
      provides a roadmap that draws on the content of the continued process
      verification case study to provide a step-by-step guide in a more accessible
      form, with reference to a process map of the product life cycle. It could be used
      as a basis for continued process verification implementation in a number of
      different scenarios: For a single product and process;For a single site;To assist
      in the sharing of data monitoring responsibilities among sites;To assist in
      establishing data monitoring agreements between a customer company and a contract
      manufacturing organization. LAY ABSTRACT: The U.S. Food and Drug Administration
      issued guidance on the management of manufacturing processes designed to improve
      quality and control of drug products. This involved increased focus on regular
      monitoring of manufacturing processes, reporting of the results, and the taking
      of opportunities to improve. The guidance and practice associated with it is
      known as continued process verification This paper summarizes good practice in
      responding to continued process verification guidance, gathered from subject
      matter experts in the biopharmaceutical industry.

PMID- 27020645
TI  - Retrospective Evaluation of Low-pH Viral Inactivation and Viral Filtration Data
      from a Multiple Company Collaboration.
AB  - Considerable resources are spent within the biopharmaceutical industry to perform
      viral clearance studies, which are conducted for widely used unit operations that
      are known to have robust and effective retrovirus clearance capability. The
      collaborative analysis from the members of the BioPhorum Development Group Viral
      Clearance Working Team considers two common virus reduction steps in
      biopharmaceutical processes: low-pH viral inactivation and viral filtration.
      Analysis included eight parameters for viral inactivation and nine for viral
      filtration. The extensive data set presented in this paper provides the industry
      with a reference point for establishing robust processes in addition to other
      protocols available in the literature (e.g., ASTM Std. E2888-12 for low-pH
      inactivation). In addition, it identifies points of weakness in the existing data
      set and instructs the design and interpretation of future studies. Included is an
      abundance of data that would have been difficult to generate individually but
      collectively will help support modular viral clearance claims. 

PMID- 27020646
TI  - BPOG Response to Annex 2.

PMID- 27020647
TI  - Plasma Decontamination: A Case Study on Kill Efficacy of Geobacillus
      stearothermophilus Spores on Different Carrier Materials.
AB  - A new technology to the pharmaceutical field is presented: surface
      decontamination by plasmas The technology is comparable to established barrier
      systems like e-beam, volatile hydrogen peroxide, or radiation inactivation of
      microbiological contaminations. This plasma technology is part of a fully
      automated and validated syringe filling line at a major pharmaceutical company
      and is in production operation. Incoming pre-sterilized syringe containers
      ("tubs") are processed by plasma, solely on the outside, and passed into the
      aseptic filling isolator upon successful decontamination. The objective of this
      article is to present the operating principles and develop and establish a
      validation routine on the basis of standard commercial biological indicators.
      Their decontamination efficacies are determined and correlated to the actual
      inactivation efficacy on the pharmaceutical packaging material.The reference
      setup is explained in detail and a short presentation of the cycle development
      and the relevant plasma control parameters is given, with a special focus on the
      in-process monitor determining the cycle validity. Different microbial
      inactivation mechanisms are also discussed and evaluated for their contribution
      and interaction to enhance plasma decontamination. A material-dependent
      inactivation behavior was observed. In order to be able to correlate the tub
      surface inactivation of Geobacillus stearothermophilus endospores to metallic
      biological indicators, a comparative study was performed. Through consistently
      demonstrating the linear inactivation behavior between the different materials,
      it becomes possible to develop an effective and time-saving validation scheme.
      LAY ABSTRACT: The challenge in new decontamination systems lies in a thorough
      validation of the inactivation efficacy under different operating regimes. With
      plasma, as an ionized gas, a new barrier concept is introduced into
      pharmaceutical aseptic processing of syringes. The presented system operates in
      vacuum and only decontaminates the outer surface of pre-sterilized syringe
      containers ("tubs"), before they are transferred into the aseptic area. The
      plasma does not penetrate into the tub. This article discusses the phase from
      development and test germ selection, across the identified sporicidal mechanisms,
      to a proposal for a validation scheme on the basis of commercially available
      biological indicators. A special focus is placed on an extensive investigation to
      establish a link between the tub surface microbial kill (polystyrene and
      Tyvek(and (2)) ) and biological indicator inactivation (stainless steel).
      Additionally, a rationale is developed on how an optical in-process monitor can
      be applied to establish a validatable limit on the base of the predetermined
      inactivation data of Geobacillus stearothermophilus endospores.

PMID- 27020648
TI  - Virus Filtration and Flow Variation: An Approach To Evaluate Any Potential Impact
      on Virus Retention.
AB  - Virus removal by filtration has been an important improvement for the safety
      margins of plasma-derived medicinal products and has become a standard
      manufacturing process step for recombinant proteins. While the mechanism of
      action was initially considered to be strictly size-based, it has recently been
      recognized that a more complex interaction of the specific filter membrane and
      its pore architecture with filtrate flow rates may potentially influence the
      level of virus removal. Based on this improved understanding, parameters beyond
      the traditional state-of-the-art may need to be included into the design and
      control of these processes, and the validity of virus removal data generated in
      small-scale models for the manufacturing scale processes may need to be
      reevaluated. This article presents a tool for the analysis of flow rate during
      manufacturing or virus-spiked small-scale runs with a focus on the effects of low
      or no flow (stop) situations on the robustness of virus removal. LAY ABSTRACT:
      Virus removal by filtration has improved safety margins of plasma-derived
      medicinal products and recombinant proteins. However, low or no flow (stop)
      situations during virus filtration may potentially affect virus removal.
      Transforming filtrate flow versus time data into histograms generates intuitively
      understandable visuals that provide a powerful tool to investigate the
      equivalence of manufacturing scale processes and down-scaled virus-spiked study
      runs, and thus to understand the robustness of virus removal for this parameter.
      With this tool at hand, lower mean flow rates during small-scale experiments are
      an elegant approach to support the robustness of virus filtration with respect to
      this parameter at manufacturing scale.

PMID- 27020649
TI  - Artificial Leaks in Container Closure Integrity Testing: Nonlinear Finite Element
      Simulation of Aperture Size Originated by a Copper Wire Sandwiched between the
      Stopper and the Glass Vial.
AB  - Container closure integrity (CCI) testing is required by different regulatory
      authorities in order to provide assurance of tightness of the container closure
      system against possible contamination, for example, by microorganisms. Microbial
      ingress CCI testing is performed by incubation of the container closure system
      with microorganisms under specified testing conditions. Physical CCI uses
      surrogate endpoints, such as coloration by dye solution ingress or gas flow
      (helium leakage testing). In order to correlate microbial CCI and physical CCI
      test methods and to evaluate the methods' capability to detect a given leak,
      artificial leaks are being introduced into the container closure system in a
      variety of different ways. In our study, artificial leaks were generated using
      inserted copper wires between the glass vial opening and rubber stopper. However,
      the insertion of copper wires introduces leaks of unknown size and shape. With
      nonlinear finite element simulations, the aperture size between the rubber
      stopper and the glass vial was calculated, depending on wire diameter and capping
      force. The dependency of the aperture size on the copper wire diameter was
      quadratic. With the data obtained, we were able to calculate the leak size and
      model leak shape. Our results suggest that the size as well as the shape of the
      artificial leaks should be taken into account when evaluating critical leak
      sizes, as flow rate does not, independently, correlate to hole size. Capping
      force also affected leak size. An increase in the capping force from 30 to 70 N
      resulted in a reduction of the aperture (leak size) by approximately 50% for all
      wire diameters. From 30 to 50 N, the reduction was approximately 33%. LAY
      ABSTRACT: Container closure integrity (CCI) testing is required by different
      regulatory authorities in order to provide assurance of tightness of the
      container closure system against contamination, for example, by microorganisms.
      Microbial ingress CCI testing is performed by incubation of the container closure
      system with microorganisms under specified testing conditions. Physical CCI uses
      surrogate endpoints, such as coloration by dye solution ingress or gas flow. In
      order to correlate microbial ingress CCI and physical CCI test methods and to
      evaluate the methods' capability to detect a given leak, artificially created
      defects (artificial leaks) are being introduced into the container closure system
      in a variety of different ways. In our study, artificial leaks were generated
      using inserted copper wires between the glass vial opening and rubber stopper. Up
      to date, the insertion of copper wires introduced leaks of unknown size and
      shape. With nonlinear finite element simulations, the effective aperture size
      between the rubber stopper and the glass vial was calculated, depending on wire
      diameter and capping force, and the leak shape was modelled. Our results suggest
      that the size as well as the shape of the artificial leaks should be taken into
      account when evaluating critical leak sizes, as flow rate does not,
      independently, correlate to the hole size.

PMID- 27020650
TI  - Hydrolysis of Polysorbate 20 and 80 by a Range of Carboxylester Hydrolases.
AB  - Degradation of the surfactant polysorbate (PS) by enzyme impurities has been
      previously suggested as a mechanism for the formation of visible and subvisible
      particles that affect product quality. Although chemical degradation pathways of
      PS, such as oxidation and acid/base hydrolysis, have been previously
      characterized, enzymatic degradation of PS remains poorly understood. In this
      report, enzyme-mediated hydrolysis of the major components of PS was monitored
      using an evaporative light scattering detection-high-performance liquid
      chromatography method. PS20 and PS80 tested contained 99% of laurate and 98%
      oleate esters, respectively, were heterogeneous with respect to head group, and
      contained a distribution of ester types. Carboxylester hydrolases tested included
      those from Pseudomonas cepacia, Thermomyces lanuginosus, Candida antarctica,
      rabbit liver, and pig pancreas. PS hydrolysis was monitored by observing the
      change in the peak area of major PS components over time and quantified using a
      parameter called t50, which was defined as the time required for each peak to
      reach 50% of its initial value. Time course experiments suggested that PS
      hydrolysis was dependent on the order of esters (mono-, di-, or triester), the
      identity of the hydrophilic head group (sorbitan or isosorbide), and the identity
      of the fatty acid ester tail (C12 vs C18:1). In addition, the pattern of PS
      hydrolysis was unique to the type of enzyme used. Importantly, we observed that
      no PS component was completely resistant to the carboxylester hydrolases tested
      here. Our results illustrate a potential fingerprint approach that could be
      useful in verifying enzyme-mediated PS degradation in drug substance and provide
      an improved understanding of the complexity of PS degradation in the presence of
      enzymes. LAY ABSTRACT: Degradation of the non-ionic surfactant polysorbate (PS)
      has been reported to lead to the formation of visible and subvisible particles
      that affect product quality. Chemical degradation pathways of PS, such as
      oxidation and acid/base hydrolysis, have been previously studied, but enzymatic
      degradation of PS remains poorly understood. In this study, enzyme-mediated
      hydrolysis of the major components in a heterogeneous mixture of PS20 or PS80 was
      monitored using an evaporative light scattering detection-high-performance liquid
      chromatography method. Carboxylester hydrolases from a broad range of organisms
      were tested, including enzymes from Pseudomonas cepacia, Thermomyces lanuginosus,
      Candida antarctica, rabbit liver, and pig pancreas. Time course experiments
      suggested that PS hydrolysis was dependent on the order of esters (mono-, di-, or
      triester), the identity of the hydrophilic head group (sorbitan or isosorbide),
      the identity of the fatty acid ester tail (C12 vs C18:1), and the identity of the
      enzyme. Importantly, no PS component was completely resistant to all the
      carboxylester hydrolases tested here. Our results illustrate a potential
      fingerprint approach that could be useful in verifying or identifying enzyme
      mediated PS degradation in drug substance and provide an improved understanding
      of the complexity of PS degradation in the presence of enzymes.

PMID- 27020651
TI  - Bundled Payments: Our Experience at an Academic Medical Center.
AB  - BACKGROUND: The landscape of health care is transitioning from a fee-for-service
      model to value-based purchasing. METHODS: We developed evidence-based clinical
      pathways and risk stratification measures to effectively implement the Bundled
      Payments for Care Improvement model of value-based purchasing. RESULTS: We
      decreased patients' length of stay, discharge to inpatient facilities, and cost
      of an episode of patient care. CONCLUSION: The bundled care payment initiative
      has been successfully implemented for Diagnosis Related Groups 469 and 470,
      delivering high-quality patient care at a reduced price.

PMID- 27020652
TI  - Report of limb girdle muscular dystrophy type 2a in 6 Iranian patients, one with
      a novel deletion in CAPN3 gene.
AB  - Calpain3 is a calcium-dependent intracellular protease involved in an autosomal
      recessive form of muscular dystrophy known as limb-girdle muscular dystrophy type
      2A. Many pathogenic mutations have been identified in calpain3, encoded by the
      CAPN3 gene, which leads to weakness of the pelvic and shoulder girdle muscles. In
      the present study, whole exome sequencing was performed on six unrelated Iranian
      families who presented with progressive muscle weakness, with a strong suspicion
      of Calpainopathies. Genetic analysis of CAPN3 gene revealed five causative
      variants which had not been reported in the Iranian population before including a
      novel 6 bp deletion (c.795_800delCATTGA) and four previously reported mutations
      (c.1939G > T, c.2243G > A, c.2257delGinsAA, and c.2380 + 2T > G). Our findings
      indicate that exome sequencing can be a very effective and affordable method to
      diagnose heterogeneous muscular dystrophies, especially in consanguineous
      populations such as Iran. 

PMID- 27020653
TI  - Self-Assembled Hierarchical Superstructures from the Benzene-1,3,5-Tricarboxamide
      Supramolecules for the Fabrication of Remote-Controllable Actuating and
      Rewritable Films.
AB  - The well-defined hierarchical superstructures constructed by the self-assembly of
      programmed supramolecules can be organized for the fabrication of remote
      controllable actuating and rewritable films. To realize this concept, we newly
      designed and synthesized a benzene-1,3,5-tricarboxamide (BTA) derivative
      (abbreviated as BTA-3AZO) containing photoresponsive azobenzene (AZO) mesogens on
      the periphery of the BTA core. BTA-3AZO was first self-assembled to nanocolumns
      mainly driven by the intermolecular hydrogen-bonds between BTA cores, and these
      self-assembled nanocolumns were further self-organized laterally to form the low
      ordered hexagonal columnar liquid crystal (LC) phase below the isotropization
      temperature. Upon cooling, a lamello-columnar crystal phase emerged at room
      temperature via a highly ordered lamello-columnar LC phase. The three-dimensional
      (3D) organogel networks consisted of fibrous and lamellar superstructures were
      fabricated in the BTA-3AZO cyclohexane-methanol solutions. By tuning the
      wavelength of light, the shape and color of the 3D networked thin films were
      remote-controlled by the conformational changes of azobenzene moieties in the BTA
      3AZO. The demonstrations of remote-controllable 3D actuating and rewritable films
      with the self-assembled hierarchical BTA-3AZO thin films can be stepping stones
      for the advanced flexible optoelectronic devices. 

PMID- 27020655
TI  - Alterations of Cyclooxygenase-2 Methylation Levels Before and After Intervention
      Trial to Prevent Gastric Cancer in a Chinese Population.
AB  - To explore the epigenetic mechanisms underlying the effects of anti-Helicobacter
      pylori (H. pylori) alone and combined with COX-2 inhibitor (celecoxib), we
      dynamically evaluated the associations between COX-2 methylation alterations and
      gastric lesion evolution during the process of interventions. In a total of 809
      trial participants COX-2 methylation levels were quantitatively detected before
      and after treatment. The self-comparison at the same stomach site for each
      subject showed significant methylation alteration differences among intervention
      groups (P < 0.001). With placebo group as reference, COX-2 methylation levels
      were decreased in anti-H. pylori [OR, 3.30; 95% confidence interval (CI), 2.16
      5.02], celecoxib (OR, 2.04; 95% CI, 1.36-3.07), and anti-H. pylori followed by
      celecoxib (OR, 2.10; 95% CI, 1.38-3.17) groups. When stratified by baseline
      histology, the three active arms significantly decreased COX-2 methylation levels
      in indefinite dysplasia/dysplasia subjects, and ORs were 3.65 (95% CI, 1.96-6.80)
      for anti-H. pylori, 2.43 (95% CI 1.34-4.39) for celecoxib, and 2.80 (95% CI, 1.52
      5.15) for anti-H. pylori followed by celecoxib, respectively. No additive effect
      on COX-2 methylation was found for anti-H. pylori followed by celecoxib than two
      treatments alone. Compared with subjects without methylation reduction, higher
      opportunity for gastric lesion regression was found in subjects with decreased
      COX-2 methylation levels, especially for indefinite dysplasia/dysplasia subjects
      (OR, 1.92; 95% CI, 1.03-3.60). These findings suggest that anti-H. pylori or
      celecoxib treatment alone could decrease COX-2 methylation levels in gastric
      mucosa. COX-2 methylation alteration was associated with the regression of
      indefinite dysplasia/dysplasia, which might serve as a potential biomarker for
      chemoprevention efficacy. Cancer Prev Res; 9(6); 484-90. (c)2016 AACR.

PMID- 27020654
TI  - Risk Stratification System for Oral Cancer Screening.
AB  - Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is
      increasing in incidence. Worldwide 5-year survival is only 50% due to delayed
      intervention with more than half of the diagnoses at stage III and IV, whereas
      earlier detection (stage I and II) yields survival rates up to 80% to 90%.
      Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels
      may facilitate oral cancer risk assessment and early intervention. This study
      used a hospital-based design with 150 cases and 150 frequency-matched controls to
      determine whether CD44 and total protein levels in oral rinses were associated
      with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol
      use, and socioeconomic status (SES). High-risk subjects receiving oral cancer
      prevention interventions as part of a community-based program (n = 150) were
      followed over 1 year to determine marker specificity and variation. CD44 >=5.33
      ng/mL was highly associated with case status [adjusted OR 14.489; 95% confidence
      interval (CI), 5.973-35.145; P < .0001, vs. reference group CD44 <2.22 ng/mL and
      protein <1.23 mg/mL]. Total protein aided prediction above CD44 alone.
      Sensitivity and specificity in the frequency-matched study was 80% and 48.7%,
      respectively. However, controls were not representative of the target screening
      population due, in part, to a high rate of prior cancer. In contrast, specificity
      in the high-risk community was 74% and reached 95% after annual retesting. Simple
      and inexpensive salivary CD44 and total protein measurements may help identify
      individuals at heightened risk for oral cancer from the millions who partake in
      risky behaviors. Cancer Prev Res; 9(6); 445-55. (c)2016 AACR.

PMID- 27020656
TI  - Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an
      Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats.
AB  - Colorectal cancer is a common cancer with high mortality rate. Despite being the
      standard anti-colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited
      therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic
      vitamin D analogue with potential antitumor properties, would enhance the
      chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of
      colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5
      FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then
      6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5
      MUg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the
      animals were euthanized and their resected colons were examined macroscopically
      and microscopically. Quantitative RT-PCR was used to measure the transcription
      activities of Wnt, beta-catenin, DKK-1, CDNK-1A, NF-kappaB, and COX-2 genes, and
      ELISA was used to quantify the protein levels of beta-catenin, COX-2, HSP90, and
      VEGF. IHC was additionally used to measure beta-catenin, HSP90, and inducible
      nitric oxide synthase (iNOS). Compared with their individual therapy, combination
      of 5-FU and paricalcitol showed more significant reducing effect on numbers of
      grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5
      FU had cooperated together to repress the expression of procancerous Wnt, beta
      catenin, NF-kappaB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the
      expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their
      monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU
      exhibits an augmenting chemopreventive effect against colorectal tumors, and
      might potentially be useful for chemoprevention in colorectal cancer patients.
      Cancer Prev Res; 9(6); 491-501. (c)2016 AACR.

PMID- 27020658
TI  - Calcium regulation in mouse mesencephalic neurons-Differential roles of
      Na(+)/Ca(2+) exchanger, mitochondria and endoplasmic reticulum.
AB  - Midbrain dopaminergic (DA) neurons are the key to finely tune the voluntary
      movement, habit and motivation. The progressive and selective degeneration of
      these neurons is a pathological hallmark of Parkinson's disease (PD). The
      susceptibility of DA neurons in the SNpc may result from differences in how
      Ca(2+) is handled. However, very little information is available about the
      mechanisms involved in the regulation of intracellular Ca(2+) concentration
      ([Ca(2+)]i) in DA neurons. In this study, the relative contributions of various
      Na(+)/Ca(2+) exchangers and their interplay with internal Ca(2+) stores,
      endoplasmic reticulum (ER) and the mitochondria, in the regulation of the
      [Ca(2+)]i of mouse mesencephalic neurons were characterized. Both the K(+)
      dependent Na(+)/Ca(2+) exchanger (NCKX) and the K(+)-independent Na(+)/Ca(2+)
      exchanger (NCX) can be detected and are functional in DA and non-DA neurons. NCX
      accounts for the larger component of Na(+)/Ca(2+) exchange activity. Single-cell
      RT-PCR analysis showed each individual neuron expressed a distinct set of the
      Na(+)/Ca(2+) exchangers. Furthermore, the Na(+)/Ca(2+) exchangers play prominent
      roles in removing [Ca(2+)]i induced by glutamate but not [Ca(2+)]i induced by
      depolarization. The mitochondria serve as a major Ca(2+) sink and are
      functionally located close to NCX. In contrast, the ER is functionally located
      close to NCKX and acts primarily as a Ca(2+) source with marginal effects. This
      study reveals that the Na(+)/Ca(2+) exchangers, the ER and the mitochondria,
      which cooperate interactively, act similarly when regulating [Ca(2+)]i in
      mesencephalic DA and non-DA neurons. The heterogeneous expression of multiple
      types of Na(+)/Ca(2+) exchangers and the quantitative differences found in
      [Ca(2+)]i regulation, together with other risk factors specific to DA neurons
      such as dopamine oxidation resulting in oxidative stress, may drive these cells
      to undergo selective degeneration.

PMID- 27020659
TI  - Immature human dendritic cells enhance their migration through KCa3.1 channel
      activation.
AB  - Migration capacity is essential for dendritic cells (DCs) to present antigen to T
      cells for the induction of immune response. The DC migration is supposed to be a
      calcium-dependent process, while not fully understood. Here, we report a role of
      the KCa3.1/IK1/SK4 channels in the migration capacity of both immature (iDC) and
      mature (mDC) human CD14(+)-derived DCs. KCa3.1 channels were shown to control the
      membrane potential of human DC and the Ca(2+) entry, which is directly related to
      migration capacities. The expression of migration marker such as CCR5 and CCR7
      was modified in both types of DCs by TRAM-34 (100nM). But, only the migration of
      iDC was decreased by use of both TRAM-34 and KCa3.1 siRNA. Confocal analyses
      showed a close localization of CCR5 with KCa3.1 in the steady state of iDC.
      Finally, the implication of KCa3.1 seems to be limited to the migration
      capacities as T cell activation of DCs appeared unchanged. Altogether, these
      results demonstrated that KCa3.1 channels have a pro-migratory effect on iDC
      migration. Our findings suggest that KCa3.1 in human iDC play a major role in
      their migration and constitute an attractive target for the cell therapy
      optimization.

PMID- 27020657
TI  - Regulation of neurogenesis by calcium signaling.
AB  - Calcium (Ca(2+)) signaling has essential roles in the development of the nervous
      system from neural induction to the proliferation, migration, and differentiation
      of neural cells. Ca(2+) signaling pathways are shaped by interactions among
      metabotropic signaling cascades, intracellular Ca(2+) stores, ion channels, and a
      multitude of downstream effector proteins that activate specific genetic
      programs. The temporal and spatial dynamics of Ca(2+) signals are widely presumed
      to control the highly diverse yet specific genetic programs that establish the
      complex structures of the adult nervous system. Progress in the last two decades
      has led to significant advances in our understanding of the functional
      architecture of Ca(2+) signaling networks involved in neurogenesis. In this
      review, we assess the literature on the molecular and functional organization of
      Ca(2+) signaling networks in the developing nervous system and its impact on
      neural induction, gene expression, proliferation, migration, and differentiation.
      Particular emphasis is placed on the growing evidence for the involvement of
      store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels in these
      processes.

PMID- 27020660
TI  - Mitochondrial dysfunctions in 7-ketocholesterol-treated 158N oligodendrocytes
      without or with alpha-tocopherol: Impacts on the cellular profil of tricarboxylic
      cycle-associated organic acids, long chain saturated and unsaturated fatty acids,
      oxysterols, cholesterol and cholesterol precursors.
AB  - In multiple sclerosis (MS) a process of white matter degradation leading to
      demyelination is observed. Oxidative stress, inflammation, apoptosis, necrosis
      and/or autophagy result together into a progressive loss of oligodendrocytes. 7
      ketocholesterol (7KC), found increased in the cerebrospinal fluid of MS patients,
      triggers a rupture of RedOx homeostasis associated with mitochondrial
      dysfunctions, aptoptosis and autophagy (oxiapoptophagy) in cultured murine
      oligodendrocytes (158N). alpha-tocopherol is able to mild the alterations induced
      by 7KC partially restoring the cellular homeostasis. In presence of 7KC, the
      amount of adherent 158N cells was decreased and oxidative stress was enhanced. An
      increase of caspase-3 and PARP degradation (evidences of apoptosis), and an
      increased LC3-II/LC3-I ratio (criterion of autophagy), were detected. These
      events were associated with a decrease of the mitochondrial membrane potential
      (DeltaPsim) and by a decrease of oxidative phosphorylation revealed by reduced
      NAD+ and ATP. The cellular lactate was higher while pyruvate, citrate, fumarate,
      succinate (tricarboxylic acid (TCA) cycle intermediates) were significantly
      reduced in exposed cells, suggesting that an impairment of mitochondrial
      respiratory functions could lead to an increase of lactate production and to a
      reduced amount of ATP and acetyl-CoA available for the anabolic pathways. The
      concentration of sterol precursors lathosterol, lanosterol and desmosterol were
      significantly reduced together with satured and unsatured long chain fatty acids
      (C16:0 - C18:0, structural elements of membrane phospholipids). Such reductions
      were milder with alpha-tocopherol. It is likely that the cell death induced by
      7KC is associated with mitochondrial dysfunctions, including alterations of
      oxidative phosphorylation, which could result from lipid anabolism dysfunctions,
      especially on TCA cycle intermediates. A better knowledge of mitochondrial
      associated dysfunctions triggered by 7KC will contribute to bring new information
      on the demyelination processes which are linked with oxidative stress and lipid
      peroxidation, especially in MS.

PMID- 27020661
TI  - Suppression of error-preceding brain activity explains exaggerated error
      monitoring in females with worry.
AB  - Anxiety is consistently associated with hyperactive neural responses to errors.
      The majority of existing research has focused on a single marker of error
      elicited brain activity-the error-related negativity (ERN), an event-related
      brain potential (ERP) elicited 50-100ms following an erroneous response. The ERN
      has accumulated growing interest for its use in clinical contexts as a potential
      biomarker and/or endophenotype. However, it is unknown whether anxiety's effects
      are specific to brain activity following erroneous responses; anxiety may affect
      processes prior to error commission, suggesting that the ERN might reflect the
      output of abnormal processing that begins before an error. Here, we examined the
      error-preceding positivity (EPP) - an ERP time-locked to the correct response
      immediately before errors - that reflects a gradual disengagement of task-focused
      attention preceding errors. Results revealed that female worriers demonstrated
      significantly attenuated EPP amplitude, indicating reduced pre-error
      disengagement. Moreover, reduced EPP mediated the relationship between worry and
      the enhanced ERN following errors. These results suggest that the temporal
      dynamics of anxiety's impact on error processing are more nuanced than previously
      thought such that effects emerge prior to the actual occurrence of an erroneous
      response.

PMID- 27020662
TI  - Determinants of peri-operative blood transfusion in a contemporary series of open
      prostatectomy for benign prostate hyperplasia.
AB  - BACKGROUND: The objective of this study was to determine the factors responsible
      for peri-operative blood transfusion in a contemporary series of open
      prostatectomy for benign prostate hyperplasia and thus offer a guide for blood
      product management for the procedure. METHODS: This was a prospective study of
      200 consecutive patients who underwent open prostatectomy for BPH from January
      2010 to September 2013 at the Korle Bu Teaching Hospital, Accra. The data
      analyzed included the pre-operative blood haemoglobin level (Hb), presence of co
      morbidities, the case type, indication for the surgery, ASA score, anaesthetic
      method used, systolic blood pressure, status of the operating surgeon, duration
      of surgery and the operative prostate weight. The transfusion of blood peri
      operatively was also documented. RESULTS: The mean age of the patients was 69.1
      years. Elective cases formed 83.5 % with refractory retention of urine being the
      commonest indication for surgery (68.0 %). The mean pre-operative Hb was 12.1
      g/dl. Consultants performed 56.0 % of the prostatectomies. Transvesical approach
      was used in 90.0 % of the cases. The mean operative time was 101.3mins (range
      35.0-240.0) with a mean operative prostate weight of 110.8 g (range 15-550 g).
      Most of the patients (82.0 %) had spinal anaesthesia. The blood transfusion rate
      was 23.5 %. The transfusion rate was significantly higher in patients with
      anaemia (p = .000), emergency cases (p = .000), the use of general anaesthesia (p
      = .002), a resident as the operating surgeons (p = .034), prostate weight >100 g
      (p = .000) and duration of surgery (p = .011). In a multivariable logistic
      regression analysis however only the pre-operative Hb (p = .000. OR 0.95, 95 % CI
      [0.035-0.257]) and the duration of surgery (p = .025, OR 1.021, 95 % CI [1.003
      1.039]) could predict blood transfusion in open prostatectomy for BPH in this
      series. CONCLUSIONS: A 'group and save' policy should be the preferred blood
      ordering procedure for patients with Hb >= 13.0 g/dl scheduled for an elective
      open prostatectomy for BPH under spinal anaesthesia. A long operative time
      however may increase the need for blood transfusion.

PMID- 27020663
TI  - Long-term efficacy of real-time continuous glucose monitoring in patients with
      brittle or high-hypoglycaemic-risk type 1 diabetes treated by insulin pump: A
      single-centre experience.

PMID- 27020665
TI  - Calibration of 57Fe Mossbauer constants by first principles.
AB  - Electron density and eigenvalues of the 3 * 3 matrix of the electric field
      gradients at the (57)Fe nuclei positions have been evaluated with the periodic ab
      initio CRYSTAL code for a wide range of crystalline compounds, adopting different
      computational approaches (Hartree-Fock, gradient corrected and hybrids
      functionals). The robust calibration procedure, involving experimental isomer
      shifts and quadrupolar splittings, yields reliable Mossbauer parameters, i.e. the
      isomer shift constant (alpha) and the nuclear quadrupolar moment (Q). Dependence
      of the results on the Hamiltonian is explored and well suited localized basis
      sets for periodic calculations are provided. 

PMID- 27020664
TI  - Incidence, Implications, and Predictors of Stent Thrombosis in Acute Myocardial
      Infarction.
AB  - Stent thrombosis (ST) remains a catastrophic problem in patients undergoing
      percutaneous coronary intervention (PCI). However, a paucity of data exist
      regarding the incidence, implications, and predictors of ST in patients with
      acute myocardial infarction (AMI). We consecutively enrolled patients with AMI in
      the CardiOvascular Risk and idEntificAtion of potential high-risk population in
      AMI registry who underwent PCI from January 2004 to December 2009 and analyzed
      definite or probable ST according to Academic Research Consortium definitions.
      The median follow-up duration was 41.9 months. Definite or probable ST occurred
      in 136 patients (3.7%), including 44 with early ST (1.0%), 38 with late ST
      (0.9%), and 54 with very late ST (2.0%). The annual incidence of very late ST
      ranged from 0.5% to 0.6%. The all-cause mortality rate after ST was 29%, which
      was higher than that for patients without ST (17%; p <0.001). The independent
      predictors of ST were no-reflow phenomenon (hazard ratio [HR] 1.96, 95%
      confidence interval [CI] 1.28 to 3.03), decreased left ventricular ejection
      fraction (HR 1.70, 95% CI 1.21 to 2.40), anemia (HR 1.54, 95% CI 1.09 to 2.18),
      and a mean stent diameter <3.0 mm (HR 1.53, 95% CI 1.04 to 2.27). ST is not
      uncommon in patients with AMI and continues to occur beyond 1 year after PCI,
      irrespective of the stent type or clinical presentation. Patients with ST are
      associated with higher mortality than patients without ST. No reflow, decreased
      left ventricular ejection fraction, anemia, and a mean stent diameter <3.0 mm are
      independent predictors of ST. 

PMID- 27020666
TI  - Synthesis of aryl trimethylstannanes from aryl halides: an efficient
      photochemical method.
AB  - An efficient transition-metal-free photochemical method featuring excellent
      functional group tolerance, mild reaction conditions and short reaction times has
      been discovered and developed for the synthesis of (hetero)aryl
      trimethylstannanes from (hetero)aryl halides. A photo-initiated radical chain
      mechanism was proposed based on preliminary mechanistic studies. 

PMID- 27020667
TI  - A proteomic analysis of mushroom polysaccharide-treated HepG2 cells.
AB  - The anti-tumor properties of fungal polysaccharides have gained significant
      recognition in Asia and tropical America. In this study, the differential
      expression of proteins in normal HepG2 cells and those treated with
      polysaccharides that had been isolated from Phellinus linteus (PL), Ganoderma
      lucidum (GL) and Auricularia auricula (AA) was investigated. Using two
      dimensional electrophoresis (2DE), a total of 104 protein spots were determined
      to be overexpressed in these cells compared with noncancerous regions. A total of
      59 differentially expressed proteins were identified through MALDI-TOF-MS. In
      addition, 400 biological processes (BP), 133 cell components (CC) and 146
      molecular functions (MF) were enriched by Gene Ontology (GO) analysis, and 78
      KEGG pathways were enriched by pathway enrichment. Protein-Protein Interaction
      (PPI) analysis demonstrated the interaction networks affected by polysaccharides
      in HepG2 cells. Then, DJ-1 and 14-3-3 were identified as the key proteins in the
      networks, and the expression of the mRNA and proteins were evaluated using Real
      time quantitative PCR (qRT-PCR) and Western blotting (WB), respectively. The
      results were in agreement with the 2DE. These results provided information on
      significant proteins of hepatocellular carcinoma (HCC) and form an important
      basis for the future development of valuable medicinal mushroom resources. 

PMID- 27020668
TI  - Latex carrier for improving protoporphyrin IX for photodynamic therapy.
AB  - Attachment of Protoporphyrin IX (PPIX) to poly (styrene-co-4-vinylpyridine)
      (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions.
      After using an oil-in-water heated emulsion polymerization technique to
      synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of
      PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing
      self-reactions between the carboxyl groups and the porphyrin core. Refraining the
      two parts from interacting while attached to the nanobeads prevented PPIX from
      aggregating, which then increased water solubility, enhanced luminescence and
      singlet oxygen production. Attachment also improved cell uptake and cell
      destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve
      aspects of photodynamic therapy for the treatment of cancer. 

PMID- 27020669
TI  - Potassium supplementation inhibits IL-17A production induced by salt loading in
      human T lymphocytes via p38/MAPK-SGK1 pathway.
AB  - High salt intake contributes to the development of autoimmune/inflammatory
      diseases, while potassium supplementation antagonizes the effects. Interleukin
      (IL)-17A are tightly related with autoimmune/inflammatory diseases. Thus, we
      explored the effects and underlying molecular mechanism of high salt and
      potassium supplementation on IL-17A production in T lymphocytes. Forty-nine
      healthy participants received a low-salt, high-salt, followed by a high-salt diet
      plus potassium supplement for 7 days, respectively. Human T lymphocyte Jurkat
      cells were treated with different concentrations of NaCl and KCl. In the
      participants, IL-17A levels in plasma and in peripheral blood mononuclear cells
      (PBMC) were significantly increased after a high-salt diet, which was
      dramatically reversed when potassium was supplemented. In Jurkat cells, the
      addition of 40 mM NaCl markedly enhanced IL-17A production and the expression of
      phosphorylated p38/mitogen-activated protein kinase (MAPK) and its downstream
      target, serum/glucocorticoid-regulated kinase (SGK)1, whereas combined treatment
      with additional 2 mM KCl significantly decreased them. Respective inhibition of
      p38/MAPK and SGK1 suppressed IL-17A expression induced by NaCl, and KCl inhibited
      IL-17A production induced by specific activator of p38/MAPK. We conclude
      potassium supplementation has a blocking effect on IL-17A production in T
      lymphocytes induced by salt loading. This protective effect is mediated through
      the direct suppression of p38/MAPK-SGK1 pathway.

PMID- 27020670
TI  - Traumatic central cord syndrome: neurological and functional outcome at 3 years.
AB  - STUDY DESIGN: Retrospective cohort analysis with prospective follow-up.
      OBJECTIVES: To evaluate neurological and functional recovery following central
      cord syndrome. SETTING: Northern Ireland, population 1.8 million. METHODS: Twenty
      seven cords were identified in 1 year. Five managed conservatively and 22 with
      surgery. American Spinal Injury Association (ASIA) motor scores (AMS) were
      calculated to assess neurological recovery. Rotterdam scores assessed functional
      independence at 3 years. RESULTS: Average age was 62 years. Mechanism of injury
      was a fall with neck hyperextension in 81% patients. Average AMS in surgical
      patients improved from injury, preoperatively, postoperatively, 6 months and 3
      years from 51, 81, 83, 90 to 96, respectively. Conservative patients improved
      from time of injury to day 10 from 57 to 86 and then fell to 84 at 6 months. By 3
      years, this had recovered to 91. There was no statistical significant difference
      in AMS (P=0.15)/change in AMS (DeltaAMS) (P=0.92) or percentage of motor deficit
      resolution (P=0.23) between groups at 3 years. Two patients underwent surgery
      within 48 h and achieved full motor recovery by 3 years, but this was not
      significant (P=0.2). ASIA score improvement had a positive correlation with age
      at injury. Patients treated with surgery had better Rotterdam scores at 3 years
      than those managed conservatively (P=0.05). CONCLUSIONS: This study confirms the
      natural history of central cord syndrome. Although it demonstrates equivocal
      neurological recovery for both groups, patients treated with surgery regained a
      greater degree of functional independence.

PMID- 27020671
TI  - Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced
      Pluripotent Stem Cell-Derived Cardiomyocytes.
AB  - Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative
      medicine clinics worldwide. Recently, alarming reports of life-threatening
      cardiac arrhythmias and cases of sudden death associated with the ingestion of
      ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed
      the effects of ibogaine and its main metabolite noribogaine on action potentials
      in human ventricular-like cardiomyocytes derived from induced pluripotent stem
      cells. Therapeutic concentrations of ibogaine and its long-lived active
      metabolite noribogaine significantly retarded action potential repolarization in
      human cardiomyocytes. These findings represent the first experimental proof that
      ibogaine application entails a cardiac arrhythmia risk for humans. In addition,
      they explain the clinically observed delayed incidence of cardiac adverse events
      several days after ibogaine intake. We conclude that therapeutic concentrations
      of ibogaine retard action potential repolarization in the human heart. This may
      give rise to a prolongation of the QT interval in the electrocardiogram and
      cardiac arrhythmias.

PMID- 27020672
TI  - Neoadjuvant chemoradiotherapy may increase the risk of severe anastomotic
      complications after esophagectomy with cervical anastomosis.
AB  - PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) improves long-term survival for
      patients with esophageal cancer. On the other hand, there are indications that
      nCRT may increase the risk for postoperative morbidity. The aims of this study
      were to estimate the radiation exposure to the site of anastomosis on the gastric
      fundus and to assess whether nCRT affected the incidence or severity of cervical
      anastomotic complications. METHODS: A retrospective cohort of patients with
      cancer of the esophagus or gastroesophageal junction, who were reconstructed with
      cervical anastomosis. The planned radiation dose to the site of the cervical
      anastomosis on the gastric fundus was estimated for each patient. RESULTS: The
      analysis of the dose plans showed that 20 out of 22 (93 %) available patients
      received radiotherapy toward the planned site of the anastomosis in the region of
      the gastric fundus with doses ranging from 6 to 40 Gy. In the nCRT group, 12 out
      of 28 patients (43 %) had anastomotic complications compared to 16 out of 42 (38
      %) in the non-RT group (p = 0.69). In the nCRT group, 39 % had anastomotic
      complications that led to a Clavien-Dindo grade of IVa or higher compared to 17 %
      in the non-RT group (p = 0.03). The OR for Clavien-Dindo grade IVa or worse was
      6.0 (95 % CI 1.52-23.50). CONCLUSION: This small retrospective study suggests
      that nCRT exposes the future anastomotic site to doses of radiation that may
      impair healing of the subsequent cervical anastomosis. Our data further suggest
      that nCRT may increase the severity of cervical anastomotic complications, and
      this hypothesis needs to be tested in a large prospective study.

PMID- 27020673
TI  - Interim estimates of 2015/16 vaccine effectiveness against influenza
      A(H1N1)pdm09, Canada, February 2016.
AB  - Using a test-negative design, the Canadian Sentinel Practitioner Surveillance
      Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against
      influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64%
      (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults
      between 20 and 64 years-old against medically attended, laboratory-confirmed
      A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were
      successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1
      subclade, defined by S162N (potential gain of glycosylation) and I216T mutations
      in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the
      2015/16 northern hemisphere vaccine provided significant protection against
      A(H1N1)pdm09 illness despite genetic evolution in circulating viruses.

PMID- 27020675
TI  - The Utilisation of Music by Casino Managers: An Interview Study.
AB  - Music is ubiquitous in retail and commercial environments, with some managers
      believing that music can enhance the customer experience, increase footfall and
      sales and improve consumer satisfaction. Casino gambling is popular in the United
      Kingdom and anecdotal evidence suggests that music is often present. However,
      little is known about the rationale for music use from the perspective of casino
      managers. In this study semi-structured interviews were conducted with five
      casino managers to establish their motivations for utilising music, the factors
      informing their choice of music and the extent to which music is used with the
      intention of influencing gambling behaviour. Results showed that casino managers
      utilised two types of music-recorded background music, often sourced via external
      music supply companies and live music. Live music was often situated away from
      the gaming floor and used primarily to accompany participation in non-gambling
      activities. Recorded background music was not used with the direct aim of
      influencing customers' gambling behaviour, but to create the right atmosphere for
      gambling and to promote certain moods within the casinos. To achieve these aims
      casino managers manipulated the tempo, volume and genre of the recorded
      background music. Casino managers also reported that some gamblers listen to
      music via portable music players, possibly with the intention of customising
      their gambling experience. This study is unique as it has provided a first-hand
      account of casino managers' implicit theories with regards to why they utilise
      music and the roles which music is considered to fulfil in casinos.

PMID- 27020674
TI  - Identification of Liver Epithelial Cell-derived Ig Expression in MU chain
      deficient mice.
AB  - Growing evidence indicates that B cells are not the only source of immunoglobulin
      (Ig). To investigate this discovery further, we used MUMT mice, which have a
      disruption of the first transmembrane exon of the MU heavy chain and do not
      express the membrane form of IgM. These mice lack mature B cells and thus serve
      as a good model to explore Ig expression by liver epithelial cells. We found that
      Ig heavy chains (MU, delta, gamma and alpha) and light chains (kappa and lambda)
      were expressed in sorted liver epithelial cells of MUMT mice. Surprisingly, each
      heavy chain class showed its respective variable region sequence characteristics
      in their variable region, instead of sharing the same VDJ usage, which suggests
      that class switching does not occur in liver epithelial cells. Moreover, the
      gamma and alpha chains, but not the MU and delta chains, showed mutations in the
      variable region, thus indicating that different classes of Ig have different
      activities. Our findings support the concept that non-B cells, liver epithelial
      cells here, can produce different classes of Ig. 

PMID- 27020676
TI  - Microautophagy in nutritive phagocytes of sea urchins.
AB  - Two types of cells were observed in germinative epithelium of male and female sea
      urchins: germ cells and somatic accessory cells; the latter referred to as
      nutritive phagocytes. At the onset of gametogenesis, nutritive phagocytes
      accumulate nutrients and greatly increase in their size. As gametogenesis
      progresses, the accumulated nutrients are transferred from nutritive phagocytes
      into developing gametes, and size of the nutritive phagocytes decreases. An
      electron microscopic study of nutritive phagocytes in sea urchins,
      Strongylocentrotus intermedius, at different stages of annual reproductive cycle
      showed for the first time that both macro- and microautophagy take place in
      nutritive phagocytes. Both processes occur simultaneously and regulate size and
      composition of nutritive phagocytes in male and female sea urchins. Nutritive
      phagocytes consume redundant cytoplasm via macroautophagy. Microautophagy is
      probably involved in consumption of redundant membranes that appear within
      nutritive phagocytes due to destruction of nutrient-storing globules,
      macroautophagy, and phagocytosis of germ cells or their remnants.

PMID- 27020677
TI  - Prospective Comparison of Blood Culture Bottles and Conventional Swabs for
      Microbial Identification of Suspected Periprosthetic Joint Infection.
AB  - BACKGROUND: Early, accurate detection of infection is vital to successful
      treatment of periprosthetic joint infection (PJI). Currently, no "gold standard"
      diagnostic testing exists. The goal of this prospective study was to compare the
      efficacy of a blood culture bottle system (BCBS) to commonly used culture swabs
      in confirming PJI in patients with high clinical suspicion. METHODS: Patients
      were selected for enrollment based on Musculoskeletal Infection Society
      guidelines for PJI. erythrocyte sedimentation rate and C-reactive protein were
      obtained before aspiration. Aspirated fluid was divided between BCBS, swab, and
      synovial fluid analysis. Forty-nine samples were analyzed. RESULTS: BCBS yielded
      41 positive cultures vs 19 with swab (P < .0001), particularly with respect to
      Staphylococcus epidermidis. There were no false positive results in the BCBS
      group, using strict Musculoskeletal Infection Society guidelines. CONCLUSION:
      BCBS increased identification of pathogens in lower extremity PJI, providing
      clinicians with a low-cost, broadly-applicable test.

PMID- 27020678
TI  - Generation and Application of Male Mice with Specific Expression of Green
      Fluorescent Protein in Germ Cells.
AB  - PURPOSE: The study aimed to generate a mouse line with green fluorescent protein
      (GFP) specifically expressed in male germ cells to assess testicular toxicity.
      PROCEDURES: The mouse line with GFP specifically expressed in male germ cells was
      generated by mating a germ cell-specific transgenic Cre male mouse with a double
      fluorescent reporter female mouse using Cre/loxP. The mouse line was administered
      ethylene glycol monomethyl ether (EGME) by oral gavage. Then, the green
      fluorescence intensity in the testes was used as an indicator to examine the
      potential for testicular toxicity testing by molecular biology, histopathology,
      and in vivo imaging techniques. RESULTS: Specific testicular GFP expression was
      observed in mice. GFP was mainly expressed in the germ cell lineage and
      concentrated in secondary spermatocytes/spermatocytes and spermatozoa. After
      administration of EGME, at the organ level, the green fluorescent intensity of
      the testes was decreased by 11 days and had disappeared by 34 days. Frozen
      testicular sections stained with DAPI showed significantly decreased green
      fluorescence in secondary spermatocytes and sperm cells. These observations were
      consistent with the testis weight and results of testicular histopathology.
      CONCLUSIONS: With the application of in vivo imaging becoming popular, this mouse
      line with GFP specifically expressed in the male germ cells may have some
      advantages for the study of reproductive toxicity.

PMID- 27020679
TI  - Biodistribution and Radiation Dosimetry of the Enterobacteriaceae-Specific
      Imaging Probe [(18)F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human
      Volunteers.
AB  - PURPOSE: [(18)F]fluorodeoxysorbitol ([(18)F]FDS) is the first radiopharmaceutical
      specific for a category of bacteria and has the potential to specifically detect
      Enterobacteriaceae infections. The purpose of this study was to testify the
      safety and investigate the biodistribution and radiation dosimetry of [(18)F]FDS
      in healthy human bodies. PROCEDURES: Six healthy subjects were intravenously
      injected with 320-520 MBq [(18)F]FDS. On each subject, 21 whole-body emission
      scans and a brain scan were conducted at settled time points within the next 4 h.
      Residence time for each source organ was determined by multi-exponential
      regression. Absorbed doses for target organs and effective dose were calculated
      via OLINDA/EXM. RESULTS: No adverse events due to [(18)F]FDS injection were
      observed in the study. The tracer was cleared rapidly from the blood pool through
      the urinary system. A small portion was cleared into the gut through the
      hepatobiliary system. The effective dose (ED) was estimated to be 0.021 +/- 0.001
      mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder
      wall (0.25 +/- 0.03 mSv/MBq). CONCLUSIONS: [(18)F]FDS is safe and well tolerated.
      The effective dose was comparable to that of other F-18 labeled radiotracers.
      [(18)F]FDS is suitable for human use from a radiation dosimetry perspective.

PMID- 27020680
TI  - The response of Serratia marcescens JG to environmental changes by quorum sensing
      system.
AB  - Many bacterial cells are known to regulate their cooperative behaviors and
      physiological processes through a molecular mechanism called quorum sensing.
      Quorum sensing in Serratia marcescens JG is mediated by the synthesis of
      autoinducer 2 (AI-2) which is a furanosyl borate diester. In this study, the
      response of quorum sensing in S. marcescens JG to environment changes such as the
      initial pH, carbon sources and boracic acid was investigated by a bioreporter and
      real-time PCR analysis. The results show that glucose can affect AI-2 synthesis
      to the greatest extent, and 2.0 % glucose can stimulate S. marcescens JG to
      produce more AI-2, with a 3.5-fold increase in activity compared with control
      culture. Furthermore, the response of quorum sensing to changes in glucose
      concentration was performed by changing the amount of luxS RNA transcripts. A
      maximum of luxS transcription appeared during the exponential growth phase when
      the glucose concentration was 20.0 g/L. AI-2 production was also slightly
      impacted by the low initial pH. It is significant for us that the addition of
      boracic acid at microdosage (0.1-0.2 g/L) can also induce AI-2 synthesis, which
      probably demonstrated the feasible fact that the 4,5-dihydroxy-2, 3-pentanedione
      cyclizes by the addition of borate and the loss of water, is hydrated and is
      converted to the final AI-2 in S. marcescens JG. 

PMID- 27020681
TI  - Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein
      alpha by producing specific immune responses and altering tumor microenvironment
      in the 4T1 murine breast cancer model.
AB  - Fibroblast activation protein alpha (FAPalpha) is a tumor stromal antigen
      overexpressed by cancer-associated fibroblasts (CAFs). CAFs are genetically more
      stable compared with the tumor cells and immunosuppressive components of the
      tumor microenvironment, rendering them excellent targets for cancer
      immunotherapy. DNA vaccines are widely applied due to their safety. To
      specifically destroy CAFs, we constructed and examined the immunogenicity and
      anti-tumor immune mechanism of a DNA vaccine expressing human FAPalpha. This
      vaccine successfully reduced 4T1 tumor growth through producing FAPalpha-specific
      cytotoxic T lymphocyte responses which could kill CAFs, and the decrease in
      FAPalpha-expressing CAFs resulted in markedly attenuated expression of collagen I
      and other stromal factors that benefit the tumor progression. Based on these
      results, a DNA vaccine targeting human FAPalpha may be an attractive and
      effective cancer immunotherapy strategy. 

PMID- 27020683
TI  - Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free
      fatty acid receptor 1 agonists for the treatment of type 2 diabetes.
AB  - The free fatty acid receptor 1 (FFA1) has gained significant interest as a novel
      antidiabetic target. Most of FFA1 agonists reported in the literature bearing a
      common biphenyl scaffold, which was crucial for toxicity verified by the
      researchers of Daiichi Sankyo. Herein, we describe the systematic exploration of
      non-biphenyl scaffold and further chemical modification of the optimal pyrrole
      scaffold. All of these efforts led to the identification of compound 11 as a
      potent and orally bioavailable FFA1 agonist without the risk of hypoglycemia.
      Further molecular modeling studies promoted the understanding of ligand-binding
      pocket and might help to design more promising FFA1 agonists. 

PMID- 27020684
TI  - Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on
      primer-template models and exploration of a substrate-based FEN1 inhibitor.
AB  - Flap structure-specific endonuclease 1 (FEN1) is one of the enzymes that involve
      in Eukaryotic DNA replication and repair. Recent studies have proved that FEN1 is
      highly over-expressed in various types of cancer cells and is a drug target.
      However, a limited number of FEN1 inhibitors has been identified and approved.
      Herein, we investigate the catalytic activity of FEN1, and propose a substrate
      based inhibitor. As a consequence, one of the phosphorothioate-modified
      substrates is proved to exhibit the most efficient inhibitory effect in our in
      vitro examinations. A novelly-designed substrate-based FEN1 inhibitor was
      accordingly constructed and determined a remarkable IC50 value. 

PMID- 27020682
TI  - Tumour infiltrating lymphocytes correlate with improved survival in patients with
      oesophageal adenocarcinoma.
AB  - BACKGROUND: Oesophageal adenocarcinoma (OAC) is increasingly common in the west,
      and survival remains poor at 10-15 % at 5 years. Immune responses are
      increasingly implicated as a determining factor of tumour progression. The
      ability of lymphocytes to recognise tumour antigens provides a mechanism for a
      host immune attack against cancer providing a potential treatment strategy.
      MATERIALS AND METHODS: Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+
      and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a
      contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative
      treatment. RESULTS: Multivariate analysis identified three independent prognostic
      factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p =
      0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p
      < 0.0001). Independent prognostic factors for favourable disease-free survival
      included surgery-only treatment (p = 0.015), completeness of resection (p =
      0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p <
      0.0001). Higher levels of TILs in the pathological specimen were associated with
      significant pathological response to neoadjuvant chemotherapy (NAC). On
      multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p =
      0.005) were associated with significant local tumour regression and lymph node
      downstaging, respectively. DISCUSSION: Our results establish an association of
      TILs and survival in OAC, as seen in other solid tumours, and identify particular
      TIL subsets that are present at higher levels in patients who responded to NAC
      compared to non-responders. These findings highlight potential therapeutic
      strategies in EAC based on utilising the host immunological response and
      highlight the immune responses biomarker potential.

PMID- 27020685
TI  - Synthetic approaches to the 2014 new drugs.
AB  - New drugs introduced to the market every year represent privileged structures for
      particular biological targets. These new chemical entities (NCEs) provide insight
      into molecular recognition and also serve as leads for designing future new
      drugs. This annual review covers the synthesis of thirty-seven NCEs that were
      approved for the first time in 2014 and one drug which was approved in 2013 and
      was not covered in a previous edition of this review. 

PMID- 27020686
TI  - Nanoporous hard data: optical encoding of information within nanoporous anodic
      alumina photonic crystals.
AB  - Herein, we present a method for storing binary data within the spectral signature
      of nanoporous anodic alumina photonic crystals. A rationally designed multi
      sinusoidal anodisation approach makes it possible to engineer the photonic stop
      band of nanoporous anodic alumina with precision. As a result, the transmission
      spectrum of these photonic nanostructures can be engineered to feature well
      resolved and selectively positioned characteristic peaks across the UV-visible
      spectrum. Using this property, we implement an 8-bit binary code and assess the
      versatility and capability of this system by a series of experiments aiming to
      encode different information within the nanoporous anodic alumina photonic
      crystals. The obtained results reveal that the proposed nanosized platform is
      robust, chemically stable, versatile and has a set of unique properties for data
      storage, opening new opportunities for developing advanced nanophotonic tools for
      a wide range of applications, including sensing, photonic tagging, self-reporting
      drug releasing systems and secure encoding of information. 

PMID- 27020687
TI  - Regional Differences in Fall-Related Physical Fitness of the Elderly between
      Seoul, Korea and Gifu, Japan.
AB  - Falling is a leading cause of severe injuries among the elderly, such as hip
      fracture. This study examined the regional and sex differences in fall-related
      physical fitness of the elderly between Seoul, Korea and Gifu, Japan. The study
      included 87 elderly residents of Seoul (mean age 75.4 years; 21 males and 66
      females) and 91 elderly residents of Gifu (mean age 71.9 years; 17 males and 74
      females). The participants underwent various physical tests, and two-way ANCOVA
      (region * sex) with age as a covariate was used for statistical analysis.
      Significant interaction was shown by the one-legged stance (OLS) with eyes open
      test, which was higher in elderly females from Gifu than in those from Seoul.
      Significant main effects for the region were shown by the 30-s chair stand (CS
      30) and reaction time tests, wherein the Gifu group performed better than the
      Seoul group. Significant main effects for sex were shown by the sit and reach,
      handgrip strength, and knee extension strength tests, which were higher for
      females in the sit and reach test and lower for females in the handgrip and knee
      extension strength tests compared to the corresponding males in both the cases.
      Lastly, elderly from Gifu performed better than those from Seoul in the reaction
      time, CS-30, and OLS tests. Since the ability to move quickly and maintain
      balance to avoid falling are factors necessary for reducing fall risk, fall
      prevention classes and exercise programs are required to improve these abilities
      in the elderly. 

PMID- 27020688
TI  - Beware the impact factor.

PMID- 27020689
TI  - Perceptions of risk in communities near parks in an African biodiversity hotspot.
AB  - Understanding conservation and livelihood threats in park landscapes is important
      to informing conservation policy. To identify threats, we examined perceived
      risks of residents living near three national parks in Uganda. We used cross
      sectional household data to document, rank, and measure severity of perceived
      risks. Three risk categories, grouped into protected area, climate, and health,
      were cited by 80 % of respondents and received the highest severity scores.
      Elevation, proximity to the park, local forest loss, recent population change,
      and measures of poverty were the most important variables in predicting whether
      or not an individual identified these risks as the most or second most severe
      risk. Health issues were cited throughout the landscape, while problems
      attributed to climate (mainly insufficient rainfall) were reported to be most
      severe farther from the park. Increased population density was associated with
      increased perceived risk of health challenges, but decreased perceived risks
      attributed to the park and climate. Participatory risk mapping provides the
      opportunity to make standardized comparisons across sites, to help identify
      commonalities and differences, as a first step to examining the degree to which
      conservation management might address some of these local challenges and where
      mitigation techniques might be transferable between different sites or conflict
      scenarios. 

PMID- 27020690
TI  - Hierarchical CT to Ultrasound Registration of the Lumbar Spine: A Comparison with
      Other Registration Methods.
AB  - Three-dimensional (3D) measurement of the spine can provide important information
      for functional, developmental, diagnostic, and treatment-effect evaluations.
      However, existing measurement techniques are either 2-dimensional, highly
      invasive, or involve a high radiation dose, prohibiting their widespread and
      repeated use in both research and clinical settings. Non-invasive, non-ionizing,
      3D measurement of the spine is still beyond the current state-of-the-art. Towards
      this goal, we developed an intensity-based hierarchical CT-ultrasound
      registration approach to quantify the 3D positions and orientations of lumbar
      vertebrae from 3D freehand ultrasound and one-time computed tomography. The
      method was validated using a human dry bone specimen (T12-L5) and a porcine
      cadaver (L2-L6) by comparing the registration results with a gold standard
      fiducial-based registration. Mean (SD) target registration error and percentage
      of successful registration were 1.2 (0.6) mm and 100% for the human dry bone
      specimen, and 2.18 (0.82) mm and 92% for the porcine cadaver, indicating that the
      method is accurate and robust under clinically realistic conditions. Given that
      the use of ultrasound eliminates ionizing radiation during pose measurements, we
      believe that the hierarchical CT-ultrasound registration method is an attractive
      option for quantifying 3D poses of individual vertebra and motion segment, and
      thus warrants further investigations. 

PMID- 27020691
TI  - Clearing of fixed tissue: a review from a microscopist's perspective.
AB  - Chemical clearing of fixed tissues is becoming a key instrument for the three
      dimensional reconstruction of macroscopic tissue portions, including entire
      organs. Indeed, the growing interest in this field has both triggered and been
      stimulated by recent advances in high-throughput microscopy and data analysis
      methods, which allowed imaging and management of large samples. The strong
      entanglement between clearing methods and imaging technology is often overlooked,
      as typical classification of the former is based only on the chemicals used.
      Here, we review the recent literature in the field, proposing a taxonomy of
      clearing techniques based on their mating with the major high-throughput
      microscopies. We hope that this application-oriented classification can help
      researchers to find the protocol best suited to their experiment among the many
      present in the literature.

PMID- 27020692
TI  - Obesity is an independent risk factor for non-alcoholic fatty liver disease:
      evidence from a meta-analysis of 21 cohort studies.
AB  - BACKGROUND: The association between obesity and nonalcoholic fatty liver disease
      (NAFLD) has not been fully quantified, and the magnitude of NAFLD risk associated
      with obesity is still unclear. A meta-analysis of cohort studies was performed to
      elucidate the NAFLD risk associated with obesity. METHODS: Pubmed, Web of Science
      and Embase were searched for cohort studies assessing NAFLD risk associated with
      obesity or increased body mass index (BMI). Relative risks (RRs) with 95%
      confidence intervals (95%CIs) were pooled using random-effects model of meta
      analysis. RESULTS: Twenty-one cohort studies including 13 prospective studies and
      8 retrospective studies were finally included. There were a total of 381,655
      participants in the meta-analysis. Compared with normal weight, obesity
      independently led to a 3.5-fold increased risk of developing NAFLD (RR = 3.53,
      95%CI 2.48 to 5.03, P < 0.001). Meta-analysis also suggested an obvious dose
      dependent relationship between BMI and NAFLD risk (per 1-unit increment in BMI:
      RR = 1.20, 95%CI 1.14 to 1.26, P < 0.001). Subgroup analyses further identified
      the robustness of the association above. No obvious risk of publication bias was
      observed. CONCLUSION: Obese individuals have a 3.5-fold increased risk of
      developing NAFLD, and there is an obvious dose-dependent relationship between BMI
      and NAFLD risk. (c) 2016 World Obesity.

PMID- 27020693
TI  - Referrals for complications following hysteroscopic sterilisation:
      characteristics associated with symptomatic patients after the Essure procedure.
AB  - OBJECTIVE: This report summarises recent experience with a series of symptomatic
      Essure(r) patients with an emphasis on clinical presentation, preoperative
      imaging, surgical intervention, and outcome. METHODS: This case series presents
      Essure(r) patients (n = 7) who sought medical consultation for various
      complications. This retrospective analysis is based on consultations during a six
      month interval beginning in April 2015. RESULTS: In this sample, mean (+/- SD)
      patient age was 35.9 +/- 3.4 yrs. The gravida/parity status was 3.6 +/- 1.1 and
      2.4 +/- 1.4, respectively. Average duration of exposure to Essure(r) coils among
      these patients was 25.6 +/- 24.5 (range 5-67) months. Except for one woman, these
      patients had hysteroscopic sterilisation (HS) either with heavy sedation or under
      general anaesthesia. More than two Essure(r) devices were implanted in two women.
      Complications reported after HS included device migration, coil fragmentation,
      tissue perforation, and vaginal expulsion of Essure(r) fragment. Three of seven
      women have required hysterectomy. CONCLUSION: The current series offers evidence
      of migration of contraceptive coils as well as Essure(r) inserts perforating
      tissue and being spontaneously expelled. Evaluation of symptomatic HS patients
      should include determining how many devices have been implanted, as some women
      have more than two.

PMID- 27020694
TI  - Comparison of QOL between patients with different degenerative dementias,
      focusing especially on positive and negative affect.
AB  - BACKGROUND: Quality of life (QOL) has become an important outcome measure in the
      care of dementia patients. However, there have been few studies focusing on the
      difference in QOL between different dementias. METHODS: Two-hundred seventy-nine
      consecutive outpatients with Alzheimer's disease (AD), dementia with Lewy bodies
      (DLB) or frontotemporal dementia (FTD) were recruited. The QOL was evaluated
      objectively using the QOL Questionnaire for Dementia (QOL-D).The QOL-D comprises
      six domains: positive affect, negative affect and actions, communication,
      restlessness, attachment to others, and spontaneity. General cognition, daily
      activities, and behavioral and psychological symptoms of dementia were also
      evaluated. RESULTS: The scores of positive affect of QOL-D of AD patients were
      significantly higher than those of patients with DLB or FTD (AD 3.1 +/- 0.8, DLB
      2.6 +/- 0.9, FTD 2.6 +/- 0.7). The scores of negative affect and action of QOL-D
      of FTD patients were significantly higher than those of patients with AD or DLB
      (FTD 2.0 +/- 0.8, AD 1.4 +/- 0.5, DLB 1.5 +/- 0.6). The apathy scores of FTD and
      DLB patients were significantly higher than those of patients with AD. The
      disinhibition scores of FTD patients were significantly higher than those of
      patients with AD or DLB. CONCLUSIONS: The apathy of FTD and DLB patients and
      depression of DLB patients might affect the lower positive affect of FTD and DLB
      patients compared to AD patients. The disinhibition of FTD patients might affect
      the abundance of negative affect & actions in FTD patients compared to AD and DLB
      patients.

PMID- 27020695
TI  - Physical activity, diet quality, and mortality among sarcopenic older adults.
AB  - BACKGROUND: It is unknown if physical activity and good diet quality modify the
      risk of poor outcomes, such as mortality, among older adults with sarcopenia.
      AIM: To examine if physical activity and good diet quality modify the risk of
      poor outcomes, such as mortality, among older adults with sarcopenia. METHODS: A
      population-based cohort study among 1618 older adults with sarcopenia from the
      Third National Health and Nutrition Survey (NHANES III; 1988-1994). Sarcopenia
      was defined by the European Working Group on Sarcopenia in Older People. Physical
      activity was self-reported, and classified as sedentary (0 bouts per week),
      physically inactive (1-4 bouts per week), and physically active (>=5 bouts per
      week). Diet quality was assessed with the healthy eating index (a scale of 0-100
      representing adherence to federal dietary recommendations), and classified as
      poor (<51), fair (51-80), and good (>80) diet quality. RESULTS: Compared to
      participants who were sedentary, those who were physically inactive were 16 %
      less likely to die [HR 0.84 (95 % CI 0.64-1.09)], and those who were physically
      active were 25 % less likely to die [HR 0.75 (95 % CI 0.59-0.97); P trend =
      0.026]. Compared to participants with poor diet quality, those with fair diet
      quality were 37 % less likely to die [HR 0.63 (95 % CI 0.47-0.86)], and those
      with good diet quality were 45 % less likely to die [HR 0.55 (95 % CI 0.37-0.80);
      P trend = 0.002]. CONCLUSIONS: Participation in physical activity and consumption
      of a healthy diet correspond with a lower risk of mortality among older adults
      with sarcopenia. Randomized trials are needed in this population.

PMID- 27020696
TI  - Preoperative catheter spinal angiography and embolization of cervical spinal
      tumors: Outcomes from a single center.
AB  - OBJECTIVE: The existing literature regarding preoperative cervical spinal tumor
      embolization is sparse, with few discussions on the indications, risks, and best
      techniques. We present our experience with the preoperative endovascular
      management of hypervascular cervical spinal tumors. METHODS: We performed a
      retrospective review of all patients who underwent preoperative spinal
      angiography (regardless of whether tumor embolization was performed) at our
      institution (from 2002 to 2012) for primary and metastatic cervical spinal
      tumors. Tumor vascularity was graded from 0 (tumor blush equal to the normal
      adjacent vertebral body) to 3 (intense tumor blush with arteriovenous shunting).
      Tumors were considered "hypervascular" if they had a tumor vascular grade from 1
      to 3. Embolic materials included particles, liquid embolics, and detachable
      coils. The main embolization technique was superselective catheterization of an
      arterial tumor feeder followed by injection of embolic material. This technique
      could be used alone or supplemented with occlusion of dangerous anastomoses of
      the vertebral artery as needed to prevent inadvertent embolization of the
      vertebrobasilar system. In cases when superselective catheterization of the
      tumoral feeder was not feasible, embolization was performed from a proximal
      catheter position after occlusion of branches supplying areas other than the
      tumor ("flow diversion"). RESULTS: A total of 47 patients with 49 cervical spinal
      tumors were included in this study. Of the 49 total tumors, 41 demonstrated
      increased vascularity (vascularity score > 0). The most common tumor pathology in
      our series was renal cell carcinoma (RCC) (N = 16; 32.7% of all tumors) followed
      by thyroid carcinoma (N = 7; 14.3% of all tumors).Tumor embolization was
      undertaken in 25 hypervascular tumors resulting in complete, near-complete, and
      partial embolization in 36.0% (N = 9), 44.0% (N = 11), and 20.0% (N = 5) of
      embolized tumors, respectively. We embolized 42 tumor feeders in 25 tumors. The
      most commonly embolized tumor feeders were branches of the vertebral artery
      (19.0%; N = 8), the deep cervical artery (19.0%; N = 8), and the ascending
      cervical artery (19.0%; N = 8). Sixteen hypervascular tumors were not embolized
      because of minimal hypervascularity (8/16), unacceptably high risk of spinal cord
      or vertebrobasilar ischemia (4/16), failed superselective catheterization of
      tumor feeder (3/16), and cancellation of surgery (1/16). Vertebral artery
      occlusion was performed in 20% of embolizations. There were no new post-procedure
      neurological deficits or any serious adverse events. Estimated blood loss data
      from this cohort show a significant decrease in operative blood loss for
      embolized tumors of moderate and significant hypervascularity. CONCLUSIONS:
      Preoperative embolization of cervical spinal tumors can be performed safely and
      effectively in centers with significant experience and a standardized approach.

PMID- 27020698
TI  - Gel of chamomile vs. urea cream to prevent acute radiation dermatitis in patients
      with head and neck cancer: a randomized controlled trial.
AB  - AIM: To compare a gel made with chamomile (Chamomilla recutita) with a cream of
      urea as an intervention to delay the time to occurrence of radiation dermatitis.
      BACKGROUND: Radiation dermatitis is one of the most common adverse effects of
      radiotherapy in patients with head and neck cancer. It is characterized by
      erythema, itching, pain, skin breakage and burning sensation, and there is no
      consensus on how to prevent it. DESIGN: The study is a randomized controlled
      clinical trial. METHODS: We will recruit 48 individuals with head and neck cancer
      who will be starting their radiotherapy and randomize them to receive either gel
      of chamomile or cream of urea, as an intervention for prevention of radiation
      dermatitis. Social-demographic data will be collected at baseline, and clinical
      data will be collected before the initiation of radiotherapy. Participants will
      be followed weekly to assess development of radiation dermatitis. The protocol is
      funded by Conselho Nacional de Pesquisa e Desenvolvimento Cientifico (Brazil).
      The study was approved by a research ethics committee. DISCUSSION: Given the
      clinical relevance of preventing radiation dermatitis and the lack of evidence
      supporting specific preventive interventions, it is important to study new
      products that might be efficacious to prevent this complication. This article
      presents the protocol of a randomized controlled trial comparing a gel made with
      chamomile (intervention) with a cream of urea (control) to prevent radiation
      dermatitis in patients with head and neck cancer undergoing radiotherapy.

PMID- 27020697
TI  - Defects in TRPM7 channel function deregulate thrombopoiesis through altered
      cellular Mg(2+) homeostasis and cytoskeletal architecture.
AB  - Mg(2+) plays a vital role in platelet function, but despite implications for life
      threatening conditions such as stroke or myocardial infarction, the mechanisms
      controlling [Mg(2+)]i in megakaryocytes (MKs) and platelets are largely unknown.
      Transient receptor potential melastatin-like 7 channel (TRPM7) is a ubiquitous,
      constitutively active cation channel with a cytosolic alpha-kinase domain that is
      critical for embryonic development and cell survival. Here we report that
      impaired channel function of TRPM7 in MKs causes macrothrombocytopenia in mice
      (Trpm7(fl/fl-Pf4Cre)) and likely in several members of a human pedigree that, in
      addition, suffer from atrial fibrillation. The defect in platelet biogenesis is
      mainly caused by cytoskeletal alterations resulting in impaired proplatelet
      formation by Trpm7(fl/fl-Pf4Cre) MKs, which is rescued by Mg(2+) supplementation
      or chemical inhibition of non-muscle myosin IIA heavy chain activity.
      Collectively, our findings reveal that TRPM7 dysfunction may cause
      macrothrombocytopenia in humans and mice. 

PMID- 27020699
TI  - Intraplacental choriocarcinoma: Systematic review and management guidance.
AB  - BACKGROUND: Intraplacental choriocarcinoma (IC) is a rare form of malignant
      gestational trophoblastic disease (GTD). We present a review of 62 cases,
      including four previously unreported, and a suggested management algorithm.
      PATIENTS AND METHODS: IC cases and clinical data were identified within the
      Charing Cross Hospital (CXH) national GTD database (1986-2014) and by systematic
      literature search (1949-2014). RESULTS: 62 cases were identified including eight
      from CXH representing 0.03% of all GTD (n=27,101) diagnosed between 1986 and
      2014. Most cases were identified in the third trimester (n=52; 84%) among
      asymptomatic women (n=31; 50%) and with macroscopically normal placenta in 29%
      (18/62). In 29 non-metastatic cases with available data, 4 (14%) underwent
      adjuvant chemotherapy and 25 (86%) surveillance only, one of whom relapsed with
      metastatic disease cured with multi-agent chemotherapy. In 32 patients with
      metastatic disease (31 at presentation and one with relapse during surveillance),
      all 18 treated since 1990 achieved complete remission with multi-agent
      chemotherapy. Among 58 cases with available data, there were 20 fetal deaths and
      38 live births with 2 neonatal deaths. Of the two (5%) cases of infantile
      choriocarcinoma, one was cured with intensive therapy and the other died shortly
      after commencing single agent treatment. A further neonatal death was due to
      fetomaternal haemorrhage. CONCLUSIONS: IC usually occurs in the third trimester
      and is often asymptomatic with no macroscopic placental abnormalities. Prognosis
      with current therapy is generally excellent, even for patients presenting with
      metastatic disease. Around 60% of pregnancies affected by IC result in a live
      birth with a low neonatal mortality.

PMID- 27020700
TI  - Survival impact based on the thoroughness of pelvic lymphadenectomy in
      intermediate- or high-risk groups of endometrioid-type endometrial cancer: A
      multi-center retrospective cohort analysis.
AB  - OBJECTIVE: To investigate whether the number of lymph nodes obtained during
      lymphadenectomy affects the survival of patients with intermediate- or high-risk
      endometrioid-type endometrial cancer. METHODS: A total of 476 patients who were
      diagnosed with FIGO stage IB to IIIC2 endometrioid adenocarcinoma through
      surgical staging, including hysterectomy and pelvic lymphadenectomy with or
      without paraaortic lymphadenectomy between 2000 and 2013 were retrospectively
      enrolled from four tertiary centers in Korea. Sentinel lymph node mapping was not
      performed in any patient. The number of nodes obtained and positive nodes, was
      extracted from pathologic report. RESULTS: Paraaortic lymphadenectomy was
      performed in 298 (62.6%) patients and 164 (34.4%) had stage IIIC disease. The
      isolated paraaortic lymph node metastasis rate decreased as the number of pelvic
      nodes obtained increased. In the total study population, an increase of negative
      pelvic and paraaortic nodes was associated with improved recurrence-free survival
      (RFS) and overall survival (OS) independent of other prognostic factors. In the
      node-positive group, an increase of negative pelvic nodes was an independent
      prognostic factor for RFS [hazard ratio (HR), 0.946; 95% confidence interval
      (CI), 0.906-0.988] and OS [HR, 0.907; 95% CI, 0.849-0.968]. In stage IIIC2
      patients, 14 or less negative pelvic nodes was associated with poor RFS and OS.
      CONCLUSIONS: Removing as many pelvic nodes as possible is required to warrant
      accurate nodal staging and improve survival in patients with intermediate- or
      high-risk endometrial cancer. Sentinel lymph node mapping can be a resolution to
      minimize lymph node dissection without compromising staging accuracy.

PMID- 27020701
TI  - Planar vs. three-dimensional X6(2-), X2Y4(2-), and X3Y3(2-) (X, Y = B, Al, Ga)
      metal clusters: an analysis of their relative energies through the turn-upside
      down approach.
AB  - Despite the fact that B and Al belong to the same group 13 elements, the B6(2-)
      cluster prefers the planar D2h geometry, whereas Al6(2-) favours the Oh
      structure. In this work, we analyse the origin of the relative stability of D2h
      and Oh forms in these clusters by means of energy decomposition analysis based on
      the turn-upside-down approach. Our results show that what causes the different
      trends observed is the orbital interaction term, which combined with the
      electrostatic component do (Al6(2-) and Ga6(2-)) or do not (B6(2-)) compensate
      the higher Pauli repulsion of the Oh form. Analysing the orbital interaction term
      in more detail, we find that the preference of B6(2-) for the planar D2h form has
      to be attributed to two particular molecular orbital interactions. Our results
      are in line with a dominant delocalisation force in Al clusters and the
      preference for more localised bonding in B metal clusters. For mixed clusters, we
      have found that those with more than two B atoms prefer the planar structure for
      the same reasons as for B6(2-). 

PMID- 27020702
TI  - Morphogenesis of myocardial trabeculae in the mouse embryo.
AB  - Formation of trabeculae in the embryonic heart and the remodelling that occurs
      prior to birth is a conspicuous, but poorly understood, feature of vertebrate
      cardiogenesis. Mutations disrupting trabecular development in the mouse are
      frequently embryonic lethal, testifying to the importance of the trabeculae, and
      aberrant trabecular structure is associated with several human cardiac
      pathologies. Here, trabecular architecture in the developing mouse embryo has
      been analysed using high-resolution episcopic microscopy (HREM) and three
      dimensional (3D) modelling. This study shows that at all stages from mid
      gestation to birth, the ventricular trabeculae comprise a complex meshwork of
      myocardial strands. Such an arrangement defies conventional methods of
      measurement, and an approach based upon fractal algorithms has been used to
      provide an objective measure of trabecular complexity. The extent of
      trabeculation as it changes along the length of left and right ventricles has
      been quantified, and the changes that occur from formation of the four-chambered
      heart until shortly before birth have been mapped. This approach not only
      measures qualitative features evident from visual inspection of 3D models, but
      also detects subtle, consistent and regionally localised differences that
      distinguish each ventricle and its developmental stage. Finally, the combination
      of HREM imaging and fractal analysis has been applied to analyse changes in
      embryonic heart structure in a genetic mouse model in which trabeculation is
      deranged. It is shown that myocardial deletion of the Notch pathway component
      Mib1 (Mib1(flox/flox) ; cTnT-cre) results in a complex array of abnormalities
      affecting trabeculae and other parts of the heart.

PMID- 27020703
TI  - Self-rated treatment outcomes in medical rehabilitation among German and non
      German nationals residing in Germany: an exploratory cross-sectional study.
AB  - BACKGROUND: In many European countries, foreign nationals experience, on average,
      less favorable treatment outcomes in rehabilitative care than the respective
      majority population. In Germany, this for example is reflected in a lower
      occupational performance and a higher risk of disability retirement after
      rehabilitation as analyses of routine data show. However, little is known about
      the perspective of health care users. The aim of the present study was to compare
      self-rated treatment outcomes between German and non-German nationals undergoing
      in-patient medical rehabilitation in Germany. METHODS: We analyzed data from a
      cross-sectional representative rehabilitation patient survey of 239,811 patients
      from 642 clinics in Germany who completed about 3 weeks of in-patient
      rehabilitative treatment. The self-rating of the treatment outcome was based on a
      dichotomized Likert scale consisting of three items. A multilevel logistic
      regression analysis adjusted for various demographic, socio-economic, health and
      other covariates was conducted to examine differences in the self-rated treatment
      outcome between German and non-German nationals. RESULTS: Of the 239,811
      respondents 0.9% were nationals from Turkey, 0.8% had a nationality from a former
      Yugoslavian country, 0.9% held a nationality from the South European countries
      Portugal, Spain, Italy or Greece and 1.9% were nationals from other countries.
      Non-German nationals reported a less favorable self-rated outcome than Germans.
      Adjusted odds ratios [OR] for reporting a less favorable treatment outcome were
      1.24 (95%-confidence interval [95%-CI]: 1.12-1.37) for nationals from the South
      European countries Portugal/Spain/Italy/Greece, 1.62 (95%-CI: 1.45-1.80) for
      Turkish nationals and 1.68 (95%-CI: 1.52-1.85) for nationals from Former
      Yugoslavia. CONCLUSIONS: Knowledge on health outcomes from the patients' point of
      view is important for the provision of patient-centered health care. Our study
      showed that non-German nationals report less favorable outcomes of rehabilitative
      care than Germans. This may be due to cultural and religious needs not
      sufficiently addressed by health care providers. In order to improve
      rehabilitative care for non-German nationals, rehabilitative services must become
      sensitive to the needs of this population group. Diversity management can
      contribute to this process.

PMID- 27020705
TI  - Highly-Sensitive Surface-Enhanced Raman Spectroscopy (SERS)-based Chemical Sensor
      using 3D Graphene Foam Decorated with Silver Nanoparticles as SERS substrate.
AB  - In this work, a novel platform for surface-enhanced Raman spectroscopy (SERS)
      based chemical sensors utilizing three-dimensional microporous graphene foam (GF)
      decorated with silver nanoparticles (AgNPs) is developed and applied for
      methylene blue (MB) detection. The results demonstrate that silver nanoparticles
      significantly enhance cascaded amplification of SERS effect on multilayer
      graphene foam (GF). The enhancement factor of AgNPs/GF sensor is found to be four
      orders of magnitude larger than that of AgNPs/Si substrate. In addition, the
      sensitivity of the sensor could be tuned by controlling the size of silver
      nanoparticles. The highest SERS enhancement factor of ~ 5 * 10(4) is achieved at
      the optimal nanoparticle size of 50 nm. Moreover, the sensor is capable of
      detecting MB over broad concentration ranges from 1 nM to 100 MUM. Therefore,
      AgNPs/GF is a highly promising SERS substrate for detection of chemical
      substances with ultra-low concentrations.

PMID- 27020706
TI  - Key considerations in the treatment of von Hippel-Lindau disease.

PMID- 27020704
TI  - Thiopurine S-methyltransferase testing for averting drug toxicity in patients
      receiving thiopurines: a systematic review.
AB  - AIM: Thiopurine S-methyltransferase (TPMT) testing is used in patients receiving
      thiopurines to identify enzyme deficiencies and risk for adverse drug reactions.
      It is uncertain whether genotyping is superior to phenotyping. The objectives
      were to conduct a systematic review of TPMT-test performance studies. MATERIALS &
      METHODS: Electronic and grey literature sources were searched for studies
      reporting test performance compared with a reference standard. Sixty-six eligible
      studies were appraised for quality. RESULTS: Thirty phenotype-genotype and six
      phenotype-phenotype comparisons were of high quality. The calculated sensitivity
      and specificity for genotyping to identify a homozygous mutation ranged from 0.0
      100.0% and from 97.8-100.0%, respectively. CONCLUSION: Clinical decision-makers
      require high-quality evidence of clinical validity and clinical utility of TPMT
      genotyping to ensure appropriate use in patients.

PMID- 27020707
TI  - Utility of multiplex real-time PCR in the diagnosis of extrapulmonary
      tuberculosis.
AB  - OBJECTIVE: The diagnosis of extrapulmonary tuberculosis is still a challenge
      because of its pauci-bacillary nature. The aim of the study was to evaluate the
      role of a multiplex PCR assay in the diagnosis of extrapulmonary tuberculosis and
      to compare the efficiency of two targets, IS6110 and MPB64 to detect
      Mycobacterium tuberculosis. METHODS: 150 extrapulmonary samples (61 pus/aspirate,
      46 tissue, 32 body fluids, and 11 urine) from clinically suspected cases of
      tuberculosis were included in the study. All the samples were subjected to direct
      fluorescent microscopy, TB culture (BacT/ALERT 3D, biomerieux, Durham, North
      Carolina, USA) and a Multiplexed Tandem PCR targeting two mycobacterial DNA
      sequences, IS6110 and MPB64. Master-Mix reagents and primers were prepared by
      AusDiagnostics Pvt. Ltd (Alexandria, New South Wales, Australia). The performance
      of the assay was assessed using a composite gold standard, which included
      clinical characteristics, microbiology smear as well as culture, histopathology,
      cytology, radiology, and response to antitubercular therapy. RESULTS: 20.3%,
      23.6%, and 45.3% of specimens were positive by smear, culture, and PCR,
      respectively. The sensitivity and specificity of the multiplex PCR was 91.9% and
      88.4%, respectively, using the composite gold standard. Positive and negative
      predictive values of the PCR were estimated as 85.1% and 93.8%, respectively.
      Higher positivity was observed with target IS6110 (44.6%) as compared to target
      MPB64 (18.9%). The sensitivities of IS6110 and MPB64 individual targets were
      90.3% and 64.5%, respectively, and specificities were 88.4% and 97.7%,
      respectively. CONCLUSION: PCR can play an important role in rapid and accurate
      diagnosis of extrapulmonary tuberculosis. IS6110 alone is an effective target in
      our part of the country.

PMID- 27020708
TI  - Hepatitis E virus seroprevalence among schistosomiasis patients in Northeastern
      Brazil.
AB  - BACKGROUND: Hepatitis E virus (HEV) can cause chronic infection with rapid
      progression to liver cirrhosis in immunocompromised patients. HEV seroprevalence
      in patients with Schistosoma mansoni in Brazil is unknown. We evaluated the
      prevalence of past or present HEV infection in schistosomiasis patients in
      Recife, Pernambuco, Brazil. A total of 80 patients with Schistosoma mansoni were
      consecutively enrolled in a cross-sectional study. Serum samples were tested for
      the presence of anti-HEV IgG antibodies by enzyme immunoassay (Wantai anti-HEV
      IgG, Beijing, China) and for the presence of HEV RNA using real time reverse
      transcriptase-polymerase chain reaction with primers targeting the HEV ORF2 and
      ORF3. Clinical and laboratory tests as well as abdominal ultrasound were
      performed at the same day of blood collection. RESULTS: Anti-HEV IgG was positive
      in 18.8% (15/80) of patients with SM. None of the samples tested positive for
      anti-HEV IgM or HEV-RNA. Patients with anti-HEV IgG positive presented higher
      levels of alanine aminotranferase (p=0.048) and gama-glutamil transferase
      (p=0.022) when compared to patients without anti-HEV IgG antibodies. CONCLUSION:
      This study demonstrates that the seroprevalence of HEV is high in patients with
      Schistosoma mansoni in Northeastern of Brazil. Past HEV infection is associated
      with higher frequency of liver enzymes abnormalities. HEV infection and its role
      on the severity of liver disease should be further investigated among patients
      with Schistosoma mansoni.

PMID- 27020709
TI  - HPV vaccine uptake among overweight and obese US adolescents: An analysis of the
      National Health and Nutrition Examination Survey (NHANES) 2009-2014.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccine uptake in the US is suboptimal;
      identifying risk factors associated with low vaccine uptake is critical to
      increase vaccination coverage. Some evidence suggests body mass index (BMI) is
      associated with low HPV vaccine uptake and increased risk of HPV infection in
      adults. BMI may therefore be an important factor in targeting HPV vaccine to US
      adolescents. METHODS: We investigated the relationship between BMI categories
      (underweight, normal weight, overweight and obese) and HPV vaccine uptake in 4109
      adolescents (9-18 years old) using data from the 2009 to 2014 National Health and
      Nutrition Examination Survey (NHANES). We used modified Poisson regression to
      assess the relationship between BMI and receipt of at least one HPV vaccine, and
      BMI and completion of the vaccine three-dose series. We assessed the relationship
      between BMI and age at first HPV vaccination using linear regression. RESULTS:
      Receipt of at least one dose of HPV vaccine was low in both females (35%) and
      males (10%). High BMI was not associated with initiation of the HPV vaccine
      series, age at first HPV vaccination, or completion of the HPV vaccine three-dose
      course. CONCLUSIONS: We found no evidence that high BMI is associated with
      reduced initiation or completion of the HPV vaccination series, or age at
      initiation of the three-dose course among a general population sample of US
      adolescents. Our results suggest that efforts to increase HPV vaccine uptake need
      not consider targeting by weight status at this time.

PMID- 27020710
TI  - Progress towards hepatitis B prevention through vaccination in the Western
      Pacific, 1990-2014.
AB  - Hepatitis B infections are responsible for more than 300 thousand deaths per year
      in the Western Pacific Region. Because of this high burden, the countries and
      areas of the Region established a goal of reducing hepatitis B chronic infection
      prevalence among children to less than 1% by 2017. This study was conducted to
      measure the progress in hepatitis B prevention and assess the status of
      achievement of the 2017 Regional hepatitis B control goal. A literature review
      was conducted to identify studies of hepatitis B prevalence in the countries and
      areas of the region, both before and after vaccine introduction. A mathematical
      model was applied to assess infections and deaths prevented by hepatitis B
      vaccination and hepatitis B prevalence in countries without recent empirical
      data. The majority of countries and areas (22 out of 36) were estimated to have
      over 8% prevalence of chronic hepatitis B infection among persons born before
      vaccine introduction. After introduction of hepatitis B vaccine, most countries
      and areas (24 out of 36) had chronic infection prevalence of less than 1% among
      children born after vaccine introduction. It was estimated that in the past 25
      years immunization programmes in the Western Pacific Region have averted
      7,167,128 deaths that would have occurred in the lifetime of children born
      between 1990 and 2014 if hepatitis B vaccination programmes had not been
      established. Regional prevalence among children born in 2012 was estimated to be
      0.93%, meaning that the Regional hepatitis B control goal was achieved. While
      additional efforts are needed to further reduce hepatitis B transmission in the
      region, this study demonstrates the great success of the hepatitis B vaccination
      efforts in the Western Pacific Region.

PMID- 27020711
TI  - Use of flow cytometry for characterization of human cytomegalovirus vaccine
      particles.
AB  - Despite a 40-year effort, an effective vaccine against human cytomegalovirus
      (HCMV) remains an unmet medical need. The discovery of potent neutralizing
      epitopes on the pentameric gH complex (gH/gL/UL128/130/131) has reenergized HCMV
      vaccine development. Our whole-virus vaccine candidate, currently in a Phase I
      clinical trial, is based on the attenuated AD169 strain with restored expression
      of the pentameric gH complex. Given the complexity of a whole-virus vaccine,
      improved analytical methods have been developed to better characterize
      heterogeneous viral particles released from infected cells during vaccine
      production. Here we show the utility of a commercial flow cytometer for the
      detection of individual HCMV particles, either via light scattering or using
      fluorescence after labeling of specific antigens. Rapid measurements requiring
      minimal material provide near real-time information on particle concentration,
      distributions of different particle types, and product purity. Additionally,
      utilizing immunoreagents has allowed us to characterize the distribution of key
      antigens across individual particles and particle types.

PMID- 27020712
TI  - Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in
      cattle.
AB  - Development of safe and efficacious vaccines whose potency is unaffected by long
      term storage at ambient temperature would obviate major vaccine deployment
      hurdles and limit wastage associated with breaks in the vaccine cold chain. Here,
      we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored Rift
      Valley Fever vaccine (ChAdOx1-GnGc) in cattle, following its thermostabilisation
      by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose
      and sucrose. Thermostabilised ChAdOx1-GnGc vaccine stored for 6 months at 25, 37
      or 45  degrees  C elicited comparable Rift Valley Fever virus neutralising
      antibody titres to those elicited by the 'cold chain' vaccine (stored at -80 
      degrees  C throughout) at the same dose, and these were within the range
      associated with protection against Rift Valley Fever in cattle. The results
      support the use of sugar-membrane thermostabilised vaccines in target livestock
      species.

PMID- 27020713
TI  - Waning protection of influenza vaccine against mild laboratory confirmed
      influenza A(H3N2) and B in Spain, season 2014-15.
AB  - INTRODUCTION: The 2014/15 influenza season in Spain was dominated by the
      circulation of drifted A(H3N2) and co-circulation of B viruses. We present the
      final estimates of influenza vaccine effectiveness (IVE) against confirmed
      influenza A(H3N2) and B its evolution along the season and with time since
      vaccination. METHODS: We used data collected on influenza like illness patients
      (ILI), systematically swabbed for the presence of influenza viruses within the
      Spanish Influenza Sentinel Surveillance System (SISS) and a restricted
      observational study (cycEVA). We used a test negative case-control design to
      compare influenza confirmed cases with negative controls. We estimated the IVE
      through a logistic regression model adjusting for potential confounders. The
      evolution of IVE was studied in early and late stages of the epidemic, and in
      different time intervals between receiving influenza vaccination and the onset of
      symptoms. RESULTS: At the end of the season we have found low and moderate IVE
      point estimates against influenza A(H3N2) and B, respectively, in all ages and
      target groups for vaccination. An IVE decreased from an early value of 37% to a
      late of -76% against influenza A(H3N2), and similarly, 84% vs -4% against
      Influenza B. When the onset of symptoms occurred more than three months after
      vaccination, the decrease of IVE was slower and milder against influenza B than
      against influenza A(H3N2). No significant change in the percentage of circulating
      drifted influenza A(H3N2) strains belonging to the 3c.2a and 3c.3a clades could
      be identified through the season. CONCLUSIONS: In a season dominated by drifted
      A(H3N2) circulating virus, the vaccine offered little or no protection against
      A(H3N2) infection but had a moderate protective effect against influenza B.
      Efforts should be put in developing influenza vaccines that maintain their
      protective capabilities throughout the season and could stimulate a potentially
      broad immune response against diverse influenza strains.

PMID- 27020714
TI  - Three-dimensional customized bolus for intensity-modulated radiotherapy in a
      patient with Kimura's disease involving the auricle.
AB  - In radiotherapy, a commercial bolus often does not provide a suitable fit over
      irregular surfaces. To address this issue, we fabricated a customized bolus using
      3D printing technology. The aim of our study was to evaluate the application of
      this 3D-printed bolus in a clinical setting. The patient was a 45-year-old man
      with recurrent Kimura's disease involving the auricle, receiving radiotherapy in
      our oncology department. A customized bolus, 5mm in thickness, was fabricated
      based on reconstruction of computed tomography (CT) images. The bolus was printed
      on a Dimension 1200 series SST 3D printer. Repeat CT-based simulation indicated
      an acceptable fit of the 3D-printed bolus to the target region, with a maximum
      air gap of less than 5mm at the tragus. Most of the surface area of the target
      region was covered by the 95% isodose line. The plan with the 3D-printed bolus
      improved target coverage compared to that without a bolus. And the plan with the
      3D-printed bolus yielded comparable results to those with the paraffin wax bolus.
      In conclusion, a customized bolus using a 3D printer was successfully applied to
      an irregular surface. 

PMID- 27020715
TI  - [Repeated radiation dose effect and DNA repair: Importance of the individual
      factor and the time interval between the doses].
AB  - The dose fractionation effect is a recurrent question of radiation biology
      research that remains unsolved since no model predicts the clinical effect only
      with the cumulated dose and the radiobiology of irradiated tissues. Such an
      important question is differentially answered in radioprotection, radiotherapy,
      radiology or epidemiology. A better understanding of the molecular response to
      radiation makes possible today a novel approach to identify the parameters that
      condition the fractionation effect. Particularly, the time between doses appears
      to be a key factor since it will permit, or not, the repair of certain radiation
      induced DNA damages whose repair rates are of the order of seconds, minutes or
      hours: the fractionation effect will therefore vary according to the
      functionality of the different repair pathways, whatever for tumor or normal
      tissues. 

PMID- 27020716
TI  - Conflict of interests for radiation oncologists: Harnessing disclosures from
      policy to reality.
AB  - PURPOSE: An increasing attention is being paid to disclosures of conflicts of
      interests in the field of oncology. The purpose of this study was to examine how
      radiation oncologists report their conflicts of interests with pharmaceutical or
      technology industries. MATERIALS AND METHODS: We collected the data of conflicts
      of interests disclosures in the abstract books from the annual 2012 and 2013
      meetings of the American Society for Radiation Oncology (ASTRO) in Miami (FL,
      USA), and in Atlanta (GA, USA), respectively. Geographic origins of abstracts as
      well other factors were examined. RESULTS: We identified a total of 4219
      abstracts published in the past two years. The total number of involved authors
      was of 28,283. All of the published abstracts had conflicts of interests
      disclosures. Amongst them, 563 abstracts (13.4%) reported at least one potential
      conflict of interests, in which 1264 (4.5%) declared a potential conflict of
      interests in their disclosures. Geographic distribution of abstracts with
      financial relationship was as following: 67.9%, 15.5%, 7.7% and 7.7% for USA,
      Europe, Asia/Pacifica, and Canada, respectively. Abstracts with conflict of
      interest originated from North America in 75.6% of cases. USA distribution was
      70.6% and 29.4% for Eastern and Western, respectively. CONCLUSIONS: The
      proportion of physicians declaring financial conflicts of interests remains
      extremely low, whichever geographic area authors are from. In comparison to the
      rest of the world, the US proved itself better at declaring potential links.
      Changes in medical culture and education could represent a significant step to
      improve the process of revealing conflicts of interest in medical journal as well
      as in international meetings.

PMID- 27020717
TI  - Preparation and characterization of the pH and thermosensitive magnetic molecular
      imprinted nanoparticle polymer for the cancer drug delivery.
AB  - A novel pH and thermosensitive magnetic nanoparticle polymer composite
      [poly(NIPAAM@Fe3O4 MNPs/TMSPMC/DOX)] was synthesized by radical polymerization of
      N-isopropylacrylamide (NIPAAM) and the methacrylate functionalized Fe3O4
      nanoparticles/DOX complex using AIBN and EGDMA, and used as a drug carrier for
      the DOX drug delivery. Formation of poly(NIPAAM@Fe3O4 MNPs/TMSPMC/DOX) was
      confirmed by FTIR, XRD, UV-Vis, VSM, TGA-DTA and SEM. The results showed the high
      DOX loading controls release. Moreover, it showed the lower critical solution
      temperature of 40 degrees C which can be beneficial in cancer drug delivery,
      since the temperature of cancer cells is higher than normal ones, and DOX can be
      released selectively in cancer cells.

PMID- 27020718
TI  - Diterpenes: Advances in Neurobiological Drug Research.
AB  - A significant number of studies have been performed with diterpene effect on the
      brain. Our study aims to make a systematic revision on them. The initial purpose
      of this review was to screen diterpenes with neurological activity, in particular
      those that have already been studied and published in different journals
      (databases until August 2015). The second purpose was to make an action-wise
      discussion as results viewed on them by taking into drug discovery and
      development account. Diterpenes considered in this review were selected on the
      basis of updated information on them and having sufficient information on their
      screenings. We identified several examples of diterpenes having an interest in
      further study. We have included the possible sources of them as observed in
      evidence, their known molecular neurobiological mechanisms, and the active
      constituents responsible for such activities with the doses and test systems.
      Results suggest diterpenes to have neurobiological activities like neuro
      protection, anti-epileptic, anxiolytic, anti-Alzheimer's disease, anti
      Parkinson's disease, anti-cerebral ischemia, anti-neuropathic pain, anti-neuro
      inflammatory, and many more. In conclusion, diterpenes may be the prominent
      candidates in neurobiological drug research. Copyright (c) 2016 John Wiley &
      Sons, Ltd. 

PMID- 27020719
TI  - Synthesis of covalently bonded boron-dipyrromethene-diarylethene for building a
      stable photosensitizer with photo-controlled reversibility.
AB  - We report the synthesis and characterization of a photosensitizer containing
      boron-dipyrromethene and diarylethene. The photosensitizer has photo-controlled
      reversible photosensitivity and offers potential applications in photochemical
      catalysis and the degradation of organic pollutants. 

PMID- 27020720
TI  - The effectiveness and safety of amisulpride in Chinese patients with
      schizophrenia: An 8-week, prospective, open-label, multicenter, single-arm study.
AB  - INTRODUCTION: This study evaluated the effectiveness and safety of amisulpride in
      Chinese schizophrenia patients. METHODS: A multicenter, single-arm Phase IV study
      (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8
      weeks. The primary endpoint was >=50% decrease in Positive and Negative Syndrome
      Scale total score from Baseline to Week 8. RESULTS: A total of 316 patients were
      enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295)
      achieved >=50% decrease in Positive and Negative Syndrome Scale total score from
      Baseline to Week 8. Nine patients discontinued treatment because of adverse
      events. DISCUSSION: Amisulpride had clinical effectiveness and was relatively
      well tolerated in Chinese patients with schizophrenia.

PMID- 27020721
TI  - The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid
      Syndrome.
AB  - Antiphospholipid syndrome (APS) is characterized by thrombosis (arterial, venous,
      small vessel) and/or pregnancy morbidity occurring in patients with persistently
      positive antiphospholipid antibodies (aPL). Catastrophic APS is the most severe
      form of the disease, characterized by multiple organ thromboses occurring in a
      short period and commonly associated with thrombotic microangiopathy (TMA).
      Similar to patients with complement regulatory gene mutations developing TMA,
      increased complement activation on endothelial cells plays a role in
      hypercoagulability in aPL-positive patients. In mouse models of APS, activation
      of the complement is required and interaction of complement (C) 5a with its
      receptor C5aR leads to aPL-induced inflammation, placental insufficiency, and
      thrombosis. Anti-C5 antibody and C5aR antagonist peptides prevent aPL-mediated
      pregnancy loss and thrombosis in these experimental models. Clinical studies of
      anti-C5 monoclonal antibody in aPL-positive patients are limited to a small
      number of case reports. Ongoing and future clinical studies of complement
      inhibitors will help determine the role of complement inhibition in the
      management of aPL-positive patients. 

PMID- 27020722
TI  - The Impact of Variant Philadelphia Chromosome Translocations on the Clinical
      Course of Chronic Myeloid Leukemia.
AB  - Chronic myeloid leukemia (CML) is genetically characterized by the presence of
      the reciprocal translocation t(9;22) with the formation of Philadelphia (Ph)
      chromosome. Sometimes, the Ph translocation is generated by variant
      rearrangements. The prognostic impact of the variant translocations is still
      controversial. Among the 180 patients with Ph-positive CML who were treated in
      Hacettepe University Faculty of Medicine Division of Hematology, variant
      translocations were detected, and retrospectively clinical and prognostic
      features were described. Also we performed a comprehensive literature review on
      the prognosis of such variant cases before and after tyrosine kinase inhibitor
      era. Five patients (2.7%) had variant Ph chromosomes, involved in the
      rearrangements were chromosomes 2 (2 cases), 11, 14 and 15. Patients were treated
      with imatinib or dasatinib. All patients reached a stable major molecular
      response suggesting a prognosis not worse than standard translocation
      individuals. Our present data were compatible with the data of previous studies
      indicating no difference in the prognosis between standard and variant
      translocations in tyrosine kinase inhibitors era of CML. 

PMID- 27020723
TI  - First Observation of Hemoglobin G-Waimanalo and Hemoglobin Fontainebleau Cases in
      the Turkish Population.

PMID- 27020724
TI  - Extranodal Natural Killer/T-Cell Lymphoma: A Rare Nasal-Type Case.

PMID- 27020725
TI  - Wernicke's Encephalopathy in an Acute Myeloid Leukemia Patient: A Case Study.

PMID- 27020726
TI  - Kaleidoscopic Views in the Bone Marrow: Oxalate Crystals in a Patient Presenting
      with Bicytopenia.

PMID- 27020727
TI  - An Unexpected Innocent Complication Associated with Azacitidine Treatment of
      Myelodysplastic Syndrome: Erythema Annulare Centrifugum.

PMID- 27020728
TI  - Thrombotic Microangiopathic Hemolytic Anemia without Evidence of Hemolytic Uremic
      Syndrome.

PMID- 27020729
TI  - Outcomes of bacterial meningitis in children.
AB  - OBJECTIVE: Pediatricians are well aware of the immediate risks of bacterial
      meningitis in children. However, the long-term outcome of the disease has not
      been extensively studied. We aimed: (i) to evaluate the duration and quality of
      the long-term follow-up of children diagnosed with bacterial meningitis in a
      general pediatric department, (ii) to estimate the incidence of sequelae at the
      various stages of follow-up, and (iii) to compare our data with that of other
      studies. METHODS: We conducted a retrospective study and included 34 children (3
      months-15 years) who had been hospitalized for bacterial meningitis in the
      pediatric department of a University Hospital between January 1st, 2001 and
      December 31st, 2013. RESULTS: Overall, 32% of patients presented with sequelae
      and 15% with seizures. Only one patient presented with hearing loss, but 23.5% of
      patients did not have any hearing test performed. Seven patients had a
      neuropsychological assessment performed and no severe neuropsychological sequela
      was observed in this group. The average follow-up duration increased during the
      study period (from 23 to 49months). The long-term follow-up modalities observed
      in other studies were highly variable. Assessing the incidence and severity of
      sequelae was therefore difficult. CONCLUSION: A standardized follow-up should be
      implemented by way of a national surveillance network of children presenting with
      bacterial meningitis.

PMID- 27020730
TI  - pH-Triggered Polypeptides Nanoparticles for Efficient BODIPY Imaging-Guided Near
      Infrared Photodynamic Therapy.
AB  - An efficient pH-responsive multifunctional polypeptide micelle for simultaneous
      imaging and in vitro photodynamic therapy (PDT) has been prepared. The goal here
      is to detect and treat cancer cells by near-infrared fluorescence (NIRF) imaging
      and PDT synchronously. A photosensitizer BODIPY-Br2 with efficient singlet oxygen
      generation was synthesized at first which owns both seductive abilities in
      fluorescence emission and reactive oxygen species (ROS) generation under light
      irradiation. Then, amphiphilic copolymer micelles pH-triggered disassembly were
      synthesized from N-carboxyanhydride (NCA) monomer via a ring-opening
      polymerization and click reaction for the loading of BODIPY-Br2 by hydrophobic
      interaction, and the driving force is the protonation of the
      diisopropylethylamine groups conjugated to the polypeptide side chains. In vitro
      tests performed on HepG2 cancer cells confirm that the cell suppression rate was
      improved by more than 40% in the presence of light in the presence of an
      extremely low energy density (12 J/cm(2)) with very low concentration of 5.4 MUM
      photosensitizer. At the same time, the internalization of the nanoparticles by
      cells can also be traced by NIRF imaging, indicating that the NIR nanoparticles
      presented imaging guided photodynamic therapy properties. It provides the
      potential of using polypeptide as a biodegradable carrier for NIR image-guided
      photodynamic therapy. 

PMID- 27020731
TI  - A silica-based magnetic platform decorated with mixed ligand gold nanoparticles:
      a recyclable catalyst for esterification reactions.
AB  - A novel and convenient synthetic strategy for the preparation of magnetically
      responsive silica nanospheres decorated with mixed ligand protected gold
      nanoparticles is described. Gold nanoparticles are attached to the silica surface
      via stable amide bond formation. The hierarchical nanospheres show promising
      results as reusable and efficient catalysts for esterification reactions and they
      can be recovered through a simple magnetic separation. 

PMID- 27020732
TI  - For Host's Sake: The Pluses of Parasite Preservation.
AB  - Conservation biologists now realize that parasites of endangered hosts should be
      conserved for their own sake and as part of their host's natural environment. But
      parasites should also be conserved because parasitic exposure might be crucial to
      the host's development of a fully functional immune system and hence to the
      survival of the host.

PMID- 27020733
TI  - Phase transition characteristics in the conductivity of VO2(A) nanowires: size
      and surface effects.
AB  - Transition-metal oxides have fascinating characteristics, and have been exploited
      for various applications, such as Mott transistors, optical switches and strain
      sensors, etc. Vanadium dioxide is a special and important transition-metal oxide,
      and exhibits the significant behavior of metal-insulator transition. In this
      work, single crystalline VO2(A) nanowires have been synthesized by a facile
      hydrothermal method. Due to the size and surface effects, the nanowires with
      different widths show great disparities in their hysteresis loops, phase
      transition temperatures and electrical conductivities. Our results show that the
      phase transition temperature is linearly dependent on the inverse of the nanowire
      widths, and a similar relationship between the electrical conductivity and the
      width of the nanowires has also been found. More interestingly, the first-order
      phase transition of the nanowire even coverts into high-order continuous phase
      transition when the width is below a critical size. To explore the intrinsic
      influence of the size and surface effects, the analysis of the transmission
      electron microscopy measurements showed that the rough surface structure of the
      nanowire is very different to the internal structure, and the thickness of this
      rough surface structure almost remains unchanged as the with of the nanowire
      decreases. Our results indicated that the surface structure has a remarkable
      effect on the phase transition characteristics decreasing nanowire width, and the
      suitable heterogeneous nucleation originating from the rough surface structure
      should play a crucial role in properties of the VO2(A) nanowires. Size-dependent
      phase transition features of the VO2(A) nanowires also suggest that the size and
      surface effects must be taken into consideration when designing VO2 nanodevices. 

PMID- 27020734
TI  - Significance of Low Levels of Thyroglobulin Autoantibodies Associated with
      Undetectable Thyroglobulin After Thyroidectomy for Differentiated Thyroid
      Carcinoma.
AB  - BACKGROUND: The management of patients with differentiated thyroid carcinoma
      (DTC) showing low levels of serum thyroglobulin autoantibodies (TgAb) and
      undetectable Tg after thyroidectomy is unsettled. This study sought to elucidate
      the clinical significance of low levels of TgAb and to evaluate their
      interference with Tg measurement in vitro. METHODS: Tg and TgAb levels were
      correlated with the post-thyroidectomy staging of 177 consecutive DTC patients
      undergoing (131)I ablation after total thyroidectomy (clinical study). Tg was
      measured by an immunometric assay (functional sensitivity: 0.1 ng/mL), and TgAb
      were evaluated by six assays (functional sensitivities: 1.2-96 IU/mL; positive
      cutoffs: 4-150 IU/mL). The changes in Tg concentration (Tg recovery) of diluted
      specimens from DTC patients were also measured after incubation with 67 sera from
      DTC patients with undetectable Tg and low levels of TgAb (in vitro study). DTC
      sera containing Tg were diluted serially (from 330 to 0.1 ng/mL) and incubated
      with TgAb samples; Tg was then measured. RESULTS: In the clinical study: all
      patients had residual thyroid tissue, and 10 had metastatic disease. Depending on
      the TgAb assay, median Tg values were 7.0-10.9, 0.0-5.3, and 0.0-0.0 ng/mL in
      patients with undetectable, borderline (between functional sensitivities and
      positive cutoffs), and positive TgAb, respectively (p < 0.001). An undetectable
      Tg value was associated with borderline levels of TgAb in five assays. Only two
      patients with metastatic disease had undetectable Tg; both were TgAb positive by
      three or more assays. Conversely, no patient with undetectable Tg and
      undetectable or borderline TgAb by sensitive assays had metastatic disease. In
      the in vitro study, TgAb interfered significantly with Tg recovery (p < 0.001),
      but low levels of TgAb did not abolish Tg recovery. CONCLUSIONS: While low levels
      of TgAb do not preclude Tg measurement in vitro, they can be associated with an
      undetectable Tg in DTC patients with residual thyroid tissue after thyroidectomy.
      However, the finding of low levels of TgAb by sensitive assays associated with an
      undetectable Tg rules out metastatic disease.

PMID- 27020735
TI  - Diversity of ticks (Acari: Ixodidae) infesting cheetahs (Acinoyx jubatus) at
      three breeding centres in South Africa and activity patterns of questing ticks.
AB  - Ticks were collected from 191 cheetahs at three breeding centres in North West
      and Limpopo Provinces, South Africa. Haemaphysalis elliptica, a common tick of
      large felids, was the most abundant species collected, while Amblyomma hebraeum
      and Rhipicephalus simus occurred in lower numbers. In addition to these three
      species, drag-sampling of the vegetation revealed the presence of Amblyomma
      marmoreum, Rhipicephalus (B.) decoloratus and Rhipicephalus zambeziensis. The
      presence of free-ranging antelopes, murid rodents and tortoises at the breeding
      centres probably contributed to the availability of immature tick stages on the
      vegetation. Diurnal and seasonal questing patterns of ixodid ticks were
      investigated at monthly intervals at the largest cheetah-breeding centre.
      Questing ticks were most abundant on the vegetation during the warm summer
      months. Most questing H. elliptica larvae and nymphs were collected from the
      vegetation in the early morning and late afternoon and fewest during the middle
      of the day.

PMID- 27020736
TI  - Detection of Anaplasma phagocytophilum genotypes that are potentially virulent
      for human in wild ruminants and Ixodes ricinus in Central Italy.
AB  - Human granulocytic anaplasmosis (HGA) is an emerging tick-borne zoonosis
      worldwide. As is the case for many tick-borne diseases, the epidemiological cycle
      is associated to the environmental conditions, including the presence of wild
      vertebrate reservoir hosts, vectors, climate and vegetation. In this study a
      total number of 87 spleen samples of wild ruminants carcasses from Central Italy,
      and 77 Ixodes ricinus collected from the same dead animals were screened for
      Anaplasma phagocytophilum by using Real Time PCR. A. phagocytophilum DNA was
      detected in 75%, 66.7% and 54.2% of the spleen samples from red deer (Cervus
      elaphus), Apennine chamois (Rupicapra pyrenaica ornata) and roe deer (Capreolus
      capreolus) respectively, whereas it was detected in the 31.2% of I. ricinus. A
      total of 27 positive samples were characterized by sequencing a portion of the
      groEL gene. Two A. phagocytophilum lineages could clearly be delineated from the
      phylogenetic tree. Four sequences from red deer, 2 from I. ricinus and 1 from
      Apennine chamois clustered into lineage I together with those previously
      described as virulent genotypes related to HGA. The presence of A.
      phagocytophilum DNA in the Apennine chamois represents the first report for this
      Italian endemic subspecies.

PMID- 27020737
TI  - Transient Motor Asymmetry Among Infants With Congenital Torticollis-Description,
      Characterization, and Results of Follow-Up.
AB  - AIM: The purpose of this study was to assess the prevalence of transient
      functional motor asymmetry in infants with congenital postural torticollis.
      METHODS: This was a retrospective review of the medical records of infants with
      postural torticollis. We analyzed epidemiological, obstetric, perinatal data,
      physical therapy, physician assessments, and clinical follow-up for two years
      after diagnosis. RESULTS: Of 173 children, 44 (25.4%, 95% confidence interval =
      19.5 to 32.4) demonstrated functional asymmetry. Demographic and obstetrical data
      did not differ between the asymmetry/nonasymmetry groups. Delayed motor
      development (P = 0.01) and plagiocephaly (P = 0.032) were more common in infants
      with motor asymmetry. No difference was observed in the frequency of referral for
      further neurological diagnosis between the group with functional asymmetry and
      that without asymmetry. Among the 44 patients with functional asymmetry, 78%
      depicted no evidence of torticollis by age two years, and the motor asymmetry had
      disappeared in 82%. CONCLUSION: Benign, transient functional motor asymmetry
      occurred in a quarter of infants with congenital postural torticollis. Transient
      motor delay was also significantly more common in the asymmetry group. In most
      instances, motor asymmetry and motor delay disappeared by age two years.
      Plagiocephaly was more common in the asymmetry group. Clinician awareness of this
      transient asymmetry may have avoided unnecessary diagnostic tests in these
      infants.

PMID- 27020738
TI  - Double Whammy: Trauma Leading to Sequential Bilateral Facial Nerve Palsy.

PMID- 27020739
TI  - Fast antibody fragment motion: flexible linkers act as entropic spring.
AB  - A flexible linker region between three fragments allows antibodies to adjust
      their binding sites to an antigen or receptor. Using Neutron Spin Echo
      Spectroscopy we observed fragment motion on a timescale of 7 ns with motional
      amplitudes of about 1 nm relative to each other. The mechanistic complexity of
      the linker region can be described by a spring model with Brownian motion of the
      fragments in a harmonic potential. Displacements, timescale, friction and force
      constant of the underlying dynamics are accessed. The force constant exhibits a
      similar strength to an entropic spring, with friction of the fragment matching
      the unbound state. The observed fast motions are fluctuations in pre-existing
      equilibrium configurations. The Brownian motion of domains in a harmonic
      potential is the appropriate model to examine functional hinge motions dependent
      on the structural topology and highlights the role of internal forces and
      friction to function.

PMID- 27020740
TI  - The response regulator Npun_F1278 is essential for scytonemin biosynthesis in the
      cyanobacterium Nostoc punctiforme ATCC 29133.
AB  - Following exposure to long-wavelength ultraviolet radiation (UVA), some
      cyanobacteria produce the indole-alkaloid sunscreen scytonemin. The genomic
      region associated with scytonemin biosynthesis in the cyanobacterium Nostoc
      punctiforme includes 18 cotranscribed genes. A two-component regulatory system
      (Npun_F1277/Npun_F1278) directly upstream from the biosynthetic genes was
      identified through comparative genomics and is likely involved in scytonemin
      regulation. In this study, the response regulator (RR), Npun_F1278, was evaluated
      for its ability to regulate scytonemin biosynthesis using a mutant strain of N.
      punctiforme deficient in this gene, hereafter strain Delta1278. Following UVA
      radiation, the typical stimulus to initiate scytonemin biosynthesis, Delta1278
      was incapable of producing scytonemin. A phenotypic characterization of Delta1278
      suggests that aside from the ability to produce scytonemin, the deletion of the
      Npun_F1278 gene does not affect the cellular morphology, cellular differentiation
      capability, or lipid-soluble pigment complement of Delta1278 compared to the
      wildtype. The mutant, however, had a slower specific growth rate under white
      light and produced ~2.5-fold more phycocyanin per cell under UVA than the
      wildtype. Since Delta1278 does not produce scytonemin, this study demonstrates
      that the RR gene, Npun_F1278, is essential for scytonemin biosynthesis in N.
      punctiforme. While most of the evaluated effects of this gene appear to be
      specific for scytonemin, this regulator may also influence the overall health of
      the cell and phycobiliprotein synthesis, directly or indirectly. This is the
      first study to identify a regulatory gene involved in the biosynthesis of the
      sunscreen scytonemin and posits a link between cell growth, pigment synthesis,
      and sunscreen production.

PMID- 27020741
TI  - Ancient Anxiety Pathways Influence Drosophila Defense Behaviors.
AB  - Anxiety helps us anticipate and assess potential danger in ambiguous situations
      [1-3]; however, the anxiety disorders are the most prevalent class of psychiatric
      illness [4-6]. Emotional states are shared between humans and other animals [7],
      as observed by behavioral manifestations [8], physiological responses [9], and
      gene conservation [10]. Anxiety research makes wide use of three rodent
      behavioral assays-elevated plus maze, open field, and light/dark box-that present
      a choice between sheltered and exposed regions [11]. Exposure avoidance in
      anxiety-related defense behaviors was confirmed to be a correlate of rodent
      anxiety by treatment with known anxiety-altering agents [12-14] and is now used
      to characterize anxiety systems. Modeling anxiety with a small neurogenetic
      animal would further aid the elucidation of its neuronal and molecular bases.
      Drosophila neurogenetics research has elucidated the mechanisms of fundamental
      behaviors and implicated genes that are often orthologous across species. In an
      enclosed arena, flies stay close to the walls during spontaneous locomotion [15,
      16], a behavior proposed to be related to anxiety [17]. We tested this hypothesis
      with manipulations of the GABA receptor, serotonin signaling, and stress. The
      effects of these interventions were strikingly concordant with rodent anxiety,
      verifying that these behaviors report on an anxiety-like state. Application of
      this method was able to identify several new fly anxiety genes. The presence of
      conserved neurogenetic pathways in the insect brain identifies Drosophila as an
      attractive genetic model for the study of anxiety and anxiety-related disorders,
      complementing existing rodent systems.

PMID- 27020742
TI  - The Occipital Place Area Is Causally Involved in Representing Environmental
      Boundaries during Navigation.
AB  - Thirty years of research suggests that environmental boundaries-e.g., the walls
      of an experimental chamber or room-exert powerful influence on navigational
      behavior, often to the exclusion of other cues [1-9]. Consistent with this
      behavioral work, neurons in brain structures that instantiate spatial memory
      often exhibit firing fields that are strongly controlled by environmental
      boundaries [10-15]. Despite the clear importance of environmental boundaries for
      spatial coding, however, a brain region that mediates the perception of boundary
      information has not yet been identified. We hypothesized that the occipital place
      area (OPA), a scene-selective region located near the transverse occipital sulcus
      [16], might provide this perceptual source by extracting boundary information
      from visual scenes during navigation. To test this idea, we used transcranial
      magnetic stimulation (TMS) to interrupt processing in the OPA while subjects
      performed a virtual-reality memory task that required them to learn the spatial
      locations of test objects that were either fixed in place relative to the
      boundary of the environment or moved in tandem with a landmark object. Consistent
      with our prediction, we found that TMS to the right OPA impaired spatial memory
      for boundary-tethered, but not landmark-tethered, objects. Moreover, this effect
      was found when the boundary was defined by a wall, but not when it was defined by
      a marking on the ground. These results show that the OPA is causally involved in
      boundary-based spatial navigation and suggest that the OPA is the perceptual
      source of the boundary information that controls navigational behavior.

PMID- 27020743
TI  - Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing
      during Yeast Mating.
AB  - Cell pairing is central for many processes, including immune defense, neuronal
      connection, hyphal fusion, and sexual reproduction. How does a cell orient toward
      a partner, especially when faced with multiple choices? Fission yeast
      Schizosaccharomyces pombe P and M cells, which respectively express P and M
      factor pheromones [1, 2], pair during the mating process induced by nitrogen
      starvation. Engagement of pheromone receptors Map3 and Mam2 [3, 4] with their
      cognate pheromone ligands leads to activation of the Galpha protein Gpa1 to
      signal sexual differentiation [3, 5, 6]. Prior to cell pairing, the Cdc42 GTPase,
      a central regulator of cell polarization, forms dynamic zones of activity at the
      cell periphery at distinct locations over time [7]. Here we show that Cdc42-GTP
      polarization sites contain the M factor transporter Mam1, the general secretion
      machinery, which underlies P factor secretion, and Gpa1, suggesting that these
      are sub-cellular zones of pheromone secretion and signaling. Zone lifetimes scale
      with pheromone concentration. Computational simulations of pair formation through
      a fluctuating zone show that the combination of local pheromone release and
      sensing, short pheromone decay length, and pheromone-dependent zone stabilization
      leads to efficient pair formation. Consistently, pairing efficiency is reduced in
      the absence of the P factor protease. Similarly, zone stabilization at reduced
      pheromone levels, which occurs in the absence of the predicted GTPase-activating
      protein for Ras, leads to reduction in pairing efficiency. We propose that
      efficient cell pairing relies on fluctuating local signal emission and
      perception, which become locked into place through stimulation.

PMID- 27020744
TI  - translin Is Required for Metabolic Regulation of Sleep.
AB  - Dysregulation of sleep or feeding has enormous health consequences. In humans,
      acute sleep loss is associated with increased appetite and insulin insensitivity,
      while chronically sleep-deprived individuals are more likely to develop obesity,
      metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely,
      metabolic state potently modulates sleep and circadian behavior; yet, the
      molecular basis for sleep-metabolism interactions remains poorly understood.
      Here, we describe the identification of translin (trsn), a highly conserved
      RNA/DNA binding protein, as essential for starvation-induced sleep suppression.
      Strikingly, trsn does not appear to regulate energy stores, free glucose levels,
      or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a
      consequence of general metabolic dysfunction or blunted response to starvation.
      While broadly expressed in all neurons, trsn is transcriptionally upregulated in
      the heads of flies in response to starvation. Spatially restricted rescue or
      targeted knockdown localizes trsn function to neurons that produce the tachykinin
      family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin
      neurons revealed these neurons to be required for starvation-induced sleep
      suppression. Taken together, these findings establish trsn as an essential
      integrator of sleep and metabolic state, with implications for understanding the
      neural mechanism underlying sleep disruption in response to environmental
      perturbation.

PMID- 27020745
TI  - Independent Origins of Yeast Associated with Coffee and Cacao Fermentation.
AB  - Modern transportation networks have facilitated the migration and mingling of
      previously isolated populations of plants, animals, and insects. Human activities
      can also influence the global distribution of microorganisms. The best-understood
      example is yeasts associated with winemaking. Humans began making wine in the
      Middle East over 9,000 years ago [1, 2]. Selecting favorable fermentation
      products created specialized strains of Saccharomyces cerevisiae [3, 4] that were
      transported along with grapevines. Today, S. cerevisiae strains residing in
      vineyards around the world are genetically similar, and their population
      structure suggests a common origin that followed the path of human migration [3
      7]. Like wine, coffee and cacao depend on microbial fermentation [8, 9] and have
      been globally dispersed by humans. Theobroma cacao originated in the Amazon and
      Orinoco basins of Colombia and Venezuela [10], was cultivated in Central America
      by Mesoamerican peoples, and was introduced to Europeans by Hernan Cortes in 1530
      [11]. Coffea, native to Ethiopia, was disseminated by Arab traders throughout the
      Middle East and North Africa in the 6(th) century and was introduced to European
      consumers in the 17(th) century [12]. Here, we tested whether the yeasts
      associated with coffee and cacao are genetically similar, crop-specific
      populations or genetically diverse, geography-specific populations. Our results
      uncovered populations that, while defined by niche and geography, also bear
      signatures of admixture between major populations in events independent of the
      transport of the plants. Thus, human-associated fermentation and migration may
      have affected the distribution of yeast involved in the production of coffee and
      chocolate.

PMID- 27020746
TI  - Selective Persistence of Sensorimotor Mismatch Signals in Visual Cortex of
      Behaving Alzheimer's Disease Mice.
AB  - Neurodegenerative processes in Alzheimer's disease (AD) affect the structure and
      function of neurons [1-4], resulting in altered neuronal activity patterns
      comprising neuronal hypo- and hyperactivity [5, 6] and causing the disruption of
      long-range projections [7, 8]. Impaired information processing between
      functionally connected brain areas is evident in defective visuomotor
      integration, an early sign of the disease [9-11]. The cellular and neuronal
      circuit mechanisms underlying this disruption of information processing in AD,
      however, remain elusive. Recent studies in mice suggest that visuomotor
      integration already occurs in primary visual cortex (V1), as it not only
      processes sensory input but also exhibits strong motor-related activity, likely
      driven by neuromodulatory or excitatory inputs [12-17]. Here, we probed the
      integration of visual-and motor-related-inputs in V1 of behaving APP/PS1 [18]
      mice, a well-characterized mouse model of AD, using two-photon calcium imaging.
      We find that sensorimotor signals in APP/PS1 mice are differentially affected:
      while visually driven and motor-related signals are strongly reduced, neuronal
      responses signaling a mismatch between expected and actual visual flow are
      selectively spared. We furthermore observe an increase in aberrant activity
      during quiescent states in APP/PS1 mice. Jointly, the reduction in running
      correlated activity and the enhanced aberrant activity degrade the coding
      accuracy of the network, indicating that the impairment of visuomotor integration
      in AD is already taking place at early stages of visual processing.

PMID- 27020747
TI  - A CCaMK-CYCLOPS-DELLA Complex Activates Transcription of RAM1 to Regulate
      Arbuscule Branching.
AB  - Intracellular arbuscular mycorrhiza symbiosis between plants and glomeromycotan
      fungi leads to formation of highly branched fungal arbuscules that release
      mineral nutrients to the plant host. Their development is regulated in plants by
      a mechanistically unresolved interplay between symbiosis, nutrient, and hormone
      (gibberellin) signaling. Using a positional cloning strategy and a
      retrotransposon insertion line, we identify two novel alleles of Lotus japonicus
      REDUCED ARBUSCULAR MYCORRHIZA1 (RAM1) encoding a GRAS protein. We confirm that
      RAM1 is a central regulator of arbuscule development: arbuscule branching is
      arrested in L. japonicus ram1 mutants, and ectopic expression of RAM1 activates
      genes critical for arbuscule development in the absence of fungal symbionts.
      Epistasis analysis places RAM1 downstream of CCaMK, CYCLOPS, and DELLA because
      ectopic expression of RAM1 restores arbuscule formation in cyclops mutants and in
      the presence of suppressive gibberellin. The corresponding proteins form a
      complex that activates RAM1 expression via binding of CYCLOPS to a cis element in
      the RAM1 promoter. We thus reveal a transcriptional cascade in arbuscule
      development that employs the promoter of RAM1 as integrator of symbiotic
      (transmitted via CCaMK and CYCLOPS) and hormonal (gibberellin) signals.

PMID- 27020748
TI  - A retrospective and prospective analysis of trading sex for drugs or money in
      women substance abuse treatment patients.
AB  - BACKGROUND: Trading sex for drugs or money is common in substance abuse treatment
      patients, and this study evaluated prevalence and correlates of this behavior in
      women with cocaine use disorders initiating outpatient care. In addition, we
      examined the relation of sex trading status to treatment response in relation to
      usual care versus contingency management (CM), as well as predictors of continued
      involvement in sex trading over a 9-month period. METHODS: Women (N=493)
      recruited from outpatient substance abuse treatment clinics were categorized
      according to histories of sex trading (n=215, 43.6%) or not (n=278). RESULTS:
      Women with a history of trading sex were more likely to be African American,
      older and less educated, and they had more severe employment problems and were
      more likely to be HIV positive than those without this history. Controlling for
      baseline differences, both groups responded equally to substance abuse treatment
      in terms of retention and abstinence outcomes. Fifty-four women (11.3%) reported
      trading sex within the next nine months. Predictors of continued involvement in
      trading sex included a prior history of such behaviors and achieving less
      abstinence during treatment. Each additional week of abstinence during treatment
      was associated with a 16% reduction in the likelihood of trading sex over the
      follow-up. CONCLUSIONS: Because over 40% of women receiving community-based
      treatment for cocaine use disorders have traded sex for drugs or money and more
      than 10% persist in the behavior, more intensive and directed approaches toward
      addressing this HIV risk behavior are recommended.

PMID- 27020749
TI  - A springy pendulum could describe the swing leg kinetics of human walking.
AB  - The dynamics of human walking during various walking conditions could be
      qualitatively captured by the springy legged dynamics, which have been used as a
      theoretical framework for bipedal robotics applications. However, the spring
      loaded inverted pendulum model describes the motion of the center of mass (CoM),
      which combines the torso, swing and stance legs together and does not explicitly
      inform us as to whether the inter-limb dynamics share the springy legged dynamics
      characteristics of the CoM. In this study, we examined whether the swing leg
      dynamics could also be represented by springy mechanics and whether the swing leg
      stiffness shows a dependence on gait speed, as has been observed in CoM mechanics
      during walking. The swing leg was modeled as a spring-loaded pendulum hinged at
      the hip joint, which is under forward motion. The model parameters of the loaded
      mass were adopted from body parameters and anthropometric tables, whereas the
      free model parameters for the rest length of the spring and its stiffness were
      estimated to best match the data for the swing leg joint forces. The joint forces
      of the swing leg were well represented by the springy pendulum model at various
      walking speeds with a regression coefficient of R(2)>0.8. The swing leg stiffness
      increased with walking speed and was correlated with the swing frequency, which
      is consistent with previous observations from CoM dynamics described using the
      compliant leg. These results suggest that the swing leg also shares the springy
      dynamics, and the compliant walking model could be extended to better present
      swing leg dynamics.

PMID- 27020750
TI  - Mechanical heterogeneities in the subendothelial matrix develop with age and
      decrease with exercise.
AB  - Arterial stiffening occurs with age and is associated with lack of exercise.
      Notably both age and lack of exercise are major cardiovascular risk factors.
      While it is well established that bulk arterial stiffness increases with age,
      more recent data suggest that the intima, the innermost arterial layer, also
      stiffens during aging. Micro-scale mechanical characterization of individual
      layers is important because cells primarily sense the matrix that they are in
      contact with and not necessarily the bulk stiffness of the vessel wall. To
      investigate the relationship between age, exercise, and subendothelial matrix
      stiffening, atomic force microscopy was utilized here to indent the
      subendothelial matrix of the thoracic aorta from young, aged-sedentary, and aged
      exercised mice, and elastic modulus values were compared to conventional pulse
      wave velocity measurements. The subendothelial matrix elastic modulus was
      elevated in aged-sedentary mice compared to young or aged-exercised mice, and the
      macro-scale stiffness of the artery was found to linearly correlate with the
      subendothelial matrix elastic modulus. Notably, we also found that with age,
      there exists an increase in the point-to-point variations in modulus across the
      subendothelial matrix, indicating non-uniform stiffening. Importantly, this
      heterogeneity is reversible with exercise. Given that vessel stiffening is known
      to cause aberrant endothelial cell behavior, and the spatial heterogeneities we
      find exist on a length scale much smaller than the size of a cell, these data
      suggest that further investigation in the heterogeneity of the subendothelial
      matrix elastic modulus is necessary to fully understand the effects of
      physiological matrix stiffening on cell function.

PMID- 27020751
TI  - Oxytocin decreases diurnal and nocturnal arterial blood pressure in the conscious
      unrestrained spontaneously hypertensive rat.
AB  - In this study, we assessed the effects of oxytocin (OT) on mean arterial blood
      pressure (MAP), heart rate (HR), and locomotor activity (LA) in male spontaneous
      hypertensive rats (SHR) and Sprague-Dawley (SDR) controls using telemetry. OT was
      given by intravenous injections of 0.1, 0.2 or 0.4mg/kg to assess short term
      acute effects or by daily subcutaneous injections of 0.5 or 1.0mg/kg for 5 days.
      Compared to the saline infusion, (i) intravenous OT, regardless of concentration,
      increased MAP in SHR and SDR, (ii) HR increased, but was periodically lower in
      both strains with 0.2 or 0.4mg/kg, and (iii) no effects of OT on LA were
      observed. Subcutaneous injections demonstrated that (i) 1.0mg/kg for 5days
      lowered diurnal MAP and HR in SDR and SHR, persisting for 6 days, (ii) 1.0mg/kg
      decreased nocturnal HR in SDR, (iii) 0.5 and 1.0mg/kg decreased MAP with minor
      effects on HR in the SHR, and lastly (iv) OT decreased LA mainly during the
      diurnal cycle in both strains. Our main results show that OT induces significant
      beneficial effects on cardiovascular function over several diurnal and nocturnal
      cycles in the SHR, with the most prominent effect being a robust decrease in MAP.

PMID- 27020752
TI  - Microvascular medial femoral condylar flaps in 107 consecutive reconstructions in
      the head and neck.
AB  - We have assessed the role of the medial femoral condylar flap in 107 patients who
      had reconstructions of the head and neck. We retrospectively reviewed their
      medical records for indications, complications, and outcomes. The flap was
      primarily used for coverage of alveolar ridge defects (n=67), secondly for
      defects of the facial bone, calvaria, or skull base (n=35), and thirdly for
      partial laryngeal defects (n=5). Two flaps were lost. One patient fractured a
      femur 5 weeks postoperatively. The duration of follow up ranged from 6 months to
      12 years. The medial femoral condylar flap is well-suited to individual
      reconstructions of the alveolar ridge, midface, calvaria, skull base, and part of
      the larynx with poor recipient sites. The flap does not replace other wellknown
      flaps, but offers new solutions for solving special problems in head and neck
      surgery. 

PMID- 27020753
TI  - A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to
      Ensure Embryonic Divisions.
AB  - Multiple division cycles without growth are a characteristic feature of early
      embryogenesis. The female germline loads proteins and RNAs into oocytes to
      support these divisions, which lack many quality control mechanisms operating in
      somatic cells undergoing growth. Here, we describe a small RNA-Argonaute pathway
      that ensures early embryonic divisions in C. elegans by employing catalytic
      slicing activity to broadly tune, instead of silence, germline gene expression.
      Misregulation of one target, a kinesin-13 microtubule depolymerase, underlies a
      major phenotype associated with pathway loss. Tuning of target transcript levels
      is guided by the density of homologous small RNAs, whose generation must
      ultimately be related to target sequence. Thus, the tuning action of a small RNA
      catalytic Argonaute pathway generates oocytes capable of supporting
      embryogenesis. We speculate that the specialized nature of germline chromatin led
      to the emergence of small RNA-catalytic Argonaute pathways in the female germline
      as a post-transcriptional control layer to optimize oocyte composition.

PMID- 27020754
TI  - Primary Cilium-Autophagy-Nrf2 (PAN) Axis Activation Commits Human Embryonic Stem
      Cells to a Neuroectoderm Fate.
AB  - Under defined differentiation conditions, human embryonic stem cells (hESCs) can
      be directed toward a mesendoderm (ME) or neuroectoderm (NE) fate, the first
      decision during hESC differentiation. Coupled with lineage-specific G1
      lengthening, a divergent ciliation pattern emerged within the first 24 hr of
      induced lineage specification, and these changes heralded a neuroectoderm
      decision before any neural precursor markers were expressed. By day 2, increased
      ciliation in NE precursors induced autophagy that resulted in the inactivation of
      Nrf2 and thereby relieved transcriptional activation of OCT4 and NANOG. Nrf2
      binds directly to upstream regions of these pluripotency genes to promote their
      expression and repress NE derivation. Nrf2 suppression was sufficient to rescue
      poorly neurogenic iPSC lines. Only after these events had been initiated did
      neural precursor markers get expressed at day 4. Thus, we have identified a
      primary cilium-autophagy-Nrf2 (PAN) control axis coupled to cell-cycle
      progression that directs hESCs toward NE.

PMID- 27020755
TI  - Splicing of Nascent RNA Coincides with Intron Exit from RNA Polymerase II.
AB  - Protein-coding genes in eukaryotes are transcribed by RNA polymerase II (Pol II)
      and introns are removed from pre-mRNA by the spliceosome. Understanding the time
      lag between Pol II progression and splicing could provide mechanistic insights
      into the regulation of gene expression. Here, we present two single-molecule
      nascent RNA sequencing methods that directly determine the progress of splicing
      catalysis as a function of Pol II position. Endogenous genes were analyzed on a
      global scale in budding yeast. We show that splicing is 50% complete when Pol II
      is only 45 nt downstream of introns, with the first spliced products observed as
      introns emerge from Pol II. Perturbations that slow the rate of spliceosome
      assembly or speed up the rate of transcription caused splicing delays, showing
      that regulation of both processes determines in vivo splicing profiles. We
      propose that matched rates streamline the gene expression pathway, while allowing
      regulation through kinetic competition.

PMID- 27020756
TI  - Simulating the folding of HP-sequences with a minimalist model in an
      inhomogeneous medium.
AB  - The phenomenon of protein folding is a fundamental issue in the field of the
      computational molecular biology. The protein folding inside the cells is
      performed in a highly inhomogeneous, tortuous, and correlated environment.
      Therefore, it is important to include in the theoretical studies the medium where
      the protein folding is developed. In this work we present the combination of
      three models to mimic the protein folding inside of an inhomogeneous medium. The
      models used here are Hydrophobic-Polar (HP) in 2D square arrangement,
      Evolutionary Algorithms (EA), and the Dual Site Bond Model (DSBM). The DSBM model
      is used to simulate the environment where the HP beads are folded; in this case
      the medium is correlated and is fractal-like. The analysis of five benchmark HP
      sequences shows that the inhomogeneous space provided with a given correlation
      length and fractal dimension plays an important role for correct folding of these
      sequences, which does not occur in a homogeneous space. 

PMID- 27020757
TI  - Mais Medicos program: provision of medical doctors in rural, remote and socially
      vulnerable areas of Brazil, 2013-2014.
AB  - INTRODUCTION: The Mais Medicos program was introduced in 2013 with the aim of
      reducing the shortage of doctors in priority regions and diminishing regional
      inequalities in health. One of the strategies has been to offer 3-year contracts
      for doctors to work in primary healthcare services in small towns, inland, rural,
      remote, and socially vulnerable areas. This report describes the program's
      implementation and the allocation of doctors to these target areas in 2014.
      METHODS: To describe the provision of doctors in the first year of
      implementation, we compared the doctor-to-population ratio in the 5570
      municipalities of Brazil before and after the program, based on the Federal Board
      of Medicine database (2013), and the official dataset provided by the Ministry of
      Health (2014). RESULTS: In its first public call (July 2013) 3511 municipalities
      joined the Mais Medicos program, requesting a total of 15 460 doctors; although
      the program prioritizes the recruitment of Brazilians, only 1096 nationals
      enrolled and were hired, together with 522 foreign doctors. As a consequence, an
      international cooperation agreement was set in place to recruit Cuban doctors. In
      12 months the program recruited 14 462 doctors: 79.0% Cubans, 15.9% Brazilians
      and 5.1% of other nationalities, covering 93.5% of the doctors demanded; they
      were assigned to all the 3785 municipalities enrolled. The study reveals a major
      decrease in the number of municipalities with fewer than 0.1 doctors per thousand
      inhabitants, which dropped from 374 in 2013 to 95 in 2014 (75% reduction). Of the
      total, 294 doctors were sent to work in the country's 34 Indigenous Health
      Districts (100% coverage) and 3390 doctors were deployed in municipalities
      containing certified rural maroon communities (formed centuries ago by runaway
      slaves). After 1 year of implementation, the municipalities with maroon
      communities with less than 0.1 doctors per thousand inhabitants were reduced by
      87% in the poorest north region. More than 30% of municipalities with maroon
      communities in the richest regions had more than 1.0 doctors per thousand
      inhabitants, whereas in the poorest regions fewer than 7% of municipalities
      reached that level. CONCLUSIONS: The Mais Medicos program has granted medical
      assistance to these historically overlooked populations. However, it is important
      to evaluate the mid- and long-term sustainability of this initiative.

PMID- 27020759
TI  - Efficacy of topical aflibercept versus topical bevacizumab for the prevention of
      corneal neovascularization in a rat model.
AB  - The aim of this experimental study was to compare the efficacy of topical
      aflibercept and topical bevacizumab in preventing corneal neovascularization. A
      chemical burn was created in the right central cornea of male Sprague-Dawley
      rats, followed immediately by instillation of one drop (25 mg/ml, 20 MUl volume)
      of aflibercept (15 eyes), bevacizumab (14 eyes), or saline (15 eyes). Treatment
      was repeated twice daily for 7 days. Corneal neovascularization was determined
      using corneal photographs (ImageJ) on days 1, 4, 7, 10, and histological and
      immunofluorescence studies, on day 10. Stromal immunoreactivity was evaluated 2
      days after injury in 6 rats treated singly with bevacizumab or aflibercept.
      Corneal neovascularization was observed clinically on day 4 in all groups. In the
      aflibercept group, the area of neovascularization increased from 7.38 +/- 2.23%
      on day 4 to 21.73 +/- 14.59% on day 7 and 31.0 +/- 23.61% on day 10.
      Corresponding values in the bevacizumab group were 6.04% +/- 1.81%, 51.27 +/-
      15.50%, and 54.4 +/- 11.33%, and in the control group, 8.99 +/- 1.93%, 42.6 +/-
      19.59%, and 55.15 +/- 11.54%. The area of neovascularization was significantly
      smaller on days 7 and 10 in the aflibercept group than in the control and
      bevacizumab groups (P < 0.001, all analyses), with no significant differences
      between the latter two groups (day 7, P = 0.868; day 10, P = 0.213). Clinical
      findings were compatible with the histological data and supported by
      immunofluorescence and corneal flat-mount staining. Both drugs demonstrated
      variable penetration into the corneal stroma. Topical aflibercept effectively
      inhibits corneal neovascularization in a rat model of chemical burn. These
      findings may have important therapeutic implications for humans.

PMID- 27020760
TI  - Prevalence of Peripheral Arterial Disease in Patients With Diabetic Charcot
      Neuroarthropathy.
AB  - Charcot neuroarthropathy (CN) is a serious complication of diabetes mellitus (DM)
      that can lead to pedal ulceration, infection, hospitalization, and amputation.
      Peripheral arterial disease (PAD) is also found in patients with diabetic foot
      disease; however, its prevalence in patients with CN has not been extensively
      evaluated. The aim of the present study was to evaluate the prevalence of PAD in
      a group of patients with CN (with and without ulceration) and compare this to a
      group of patients with diabetic foot ulceration (DFU) and no CN. We compared the
      lower extremity noninvasive arterial testing results of 85 patients with DM and
      CN with those from a group of 126 patients with DFU and no CN. No statistically
      significant differences were found in age, gender, type of DM (1 versus 2),
      insulin use, duration of DM, or history of dialysis between our study and control
      groups. The prevalence of PAD in the patients with CN was 40%. Compared with
      patients with DFUs, the patients with CN were less likely to have PAD (odds ratio
      0.48, 95% confidence interval 0.28 to 0.85; p = .0111), ischemia (odds ratio
      0.33, 95% confidence interval 0.16 to 0.69; p = .0033), or the need for
      revascularization (odds ratio 0.27, 95% confidence interval 0.10 to 0.73; p =
      .0097). Critical limb ischemia (great toe pressure <30 mm Hg) was 82% less likely
      in patients with CN than in patients with DFU. PAD in patients with CN is not
      uncommon; however, ischemia and the need for revascularization were significantly
      less likely than in patients with DFU without CN. 

PMID- 27020758
TI  - Retinal remodeling in human retinitis pigmentosa.
AB  - Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible
      neural degenerative disease usually caused by gene defects that disrupt the
      function or architecture of the photoreceptors. While RP can initially be a
      disease of photoreceptors, there is increasing evidence that the inner retina
      becomes progressively disorganized as the outer retina degenerates. These
      alterations have been extensively described in animal models, but remodeling in
      humans has not been as well characterized. This study, using computational
      molecular phenotyping (CMP) seeks to advance our understanding of the retinal
      remodeling process in humans. We describe cone mediated preservation of overall
      topology, retinal reprogramming in the earliest stages of the disease in retinal
      bipolar cells, and alterations in both small molecule and protein signatures of
      neurons and glia. Furthermore, while Muller glia appear to be some of the last
      cells left in the degenerate retina, they are also one of the first cell classes
      in the neural retina to respond to stress which may reveal mechanisms related to
      remodeling and cell death in other retinal cell classes. Also fundamentally
      important is the finding that retinal network topologies are altered. Our results
      suggest interventions that presume substantial preservation of the neural retina
      will likely fail in late stages of the disease. Even early intervention offers no
      guarantee that the interventions will be immune to progressive remodeling.
      Fundamental work in the biology and mechanisms of disease progression are needed
      to support vision rescue strategies.

PMID- 27020761
TI  - Reduced Postoperative Functional Length Ratio Influences Patient Satisfaction in
      First Metatarsophalangeal Joint Replacement.
AB  - Complications of first metatarsophalangeal joint metallic arthroplasty are well
      known. However, the resulting shortening of the metatarsals can lead to
      transverse metatarsalgia or medial column pain at the metatarsophalangeal joints
      by creating Morton's toe/foot, which increases pressure on the second metatarsal
      head. The effect of the functional length ratio of the first and second
      metatarsals on pain and patient satisfaction has not been rigorously evaluated.
      We evaluated the effect of the first/second metatarsal ratio on patient
      satisfaction with first metatarsophalangeal joint metallic arthroplasty. From
      October 2008 to February 2010, 34 patients (median age 66.2, range 55 to 70
      years) with hallux rigidus were treated surgically using the Toefit-Plus(TM)
      prosthesis. At a mean follow-up period of 27.5 (range 17 to 35) months, 30
      patients (88.24%) underwent re-evaluation. The functional length of the first and
      second metatarsals and the lucency around the prosthesis were evaluated.
      Statistically significant (p <= .05) improvements were found for the mean
      modified American Orthopaedic Foot and Ankle Society score (from 44 to 80), pain
      (from 7 to 3 on a 10-cm visual analog scale), and mean total range of motion
      (from 42.2 degrees  to 59.4 degrees ). Also, 20 patients (58.82%) were fully
      satisfied with the procedure (scores of 8 to 10 on a 3-point Likert scale).
      Shortening the first metatarsal reduced the functional length ratio (r = 0.95; p
      < .001) and was associated with lower patient satisfaction (r = 0.66, p = .007).
      Preoperative consideration of the first/second metatarsal functional length ratio
      could be useful in preventing medial column pain due to a relatively short first
      metatarsal to a long second metatarsal axis in the transverse plane. 

PMID- 27020762
TI  - Abiotic carbonate dissolution traps carbon in a semiarid desert.
AB  - It is generally considered that desert ecosystems release CO2 to the atmosphere,
      but recent studies in drylands have shown that the soil can absorb CO2
      abiotically. However, the mechanisms and exact location of abiotic carbon
      absorption remain unclear. Here, we used soil sterilization, (13)CO2 addition,
      and detection methods to trace (13)C in the soil of the Mu Us Desert, northern
      China. After (13)CO2 addition, a large amount of (13)CO2 was absorbed by the
      sterilised soil, and (13)C was found enriched both in the soil gaseous phase and
      dissolved inorganic carbon (DIC). Further analysis indicated that about 79.45% of
      the total (13)C absorbed by the soil was trapped in DIC, while the amount of
      (13)C in the soil gaseous phase accounted for only 0.22% of the total absorbed
      (13)C. However, about 20.33% of the total absorbed (13)C remained undetected. Our
      results suggest that carbonate dissolution might occur predominately, and the
      soil liquid phase might trap the majority of abiotically absorbed carbon. It is
      possible that the trapped carbon in the soil liquid phase leaches into the
      groundwater; however, further studies are required to support this hypothesis. 

PMID- 27020763
TI  - In situ generated highly active copper oxide catalysts for the oxygen evolution
      reaction at low overpotential in alkaline solutions.
AB  - Developing efficient water oxidation catalysts made up of earth-abundant elements
      has attracted much attention as a step toward for future clean energy production.
      Herein we report a simple one-step method to generate a low cost copper oxide
      catalyst film in situ from a copper(ii) ethylenediamine complex. The resulting
      catalyst has excellent activity toward the oxygen evolution reaction in alkaline
      solutions. A catalytic current density of 1.0 mA cm(-2) and 10 mA cm(-2) for the
      catalyst film requires the overpotentials of only ~370 mV and ~475 mV in 1.0 M
      KOH, respectively. This catalytic performance shows that the new catalyst is one
      of the best Cu-based heterogeneous OER catalysts to date. 

PMID- 27020764
TI  - Soluble heat shock protein 70 members in patients undergoing allogeneic
      hematopoietic cell transplantation.
AB  - BACKGROUND: Heat shock proteins (HSP) are highly conserved immunogenic proteins
      serving as potent danger signals. They are upregulated under stress conditions
      like fever and hypoxia. Extracellular HSP are involved in antigen presentation,
      cytokine release and maturation of antigen presenting cells. METHODS: The release
      of the inducible members of the HSP70 family, Hsp72 and Hsp70B', into the serum
      of 20 patients undergoing allogeneic hematopoietic cell transplantation and 20
      healthy donors was evaluated using enzyme linked immunosorbent assay (ELISA)
      kits. RESULTS: Eight patients (40%) did not receive anti-thymocyte globulin (ATG)
      for prophylaxis of graft versus host disease (GvHD). These patients had no
      detectable or low serum levels of Hsp72 (n=3, 0.03 to 1.92ng/ml) which were in
      line with levels detected in 20 healthy individuals (p=0.07). Measurable HSP was
      not associated with any medication or transplantation-related procedures. In
      twelve patients (60%) receiving ATG, detected high levels of HSP reflected cross
      reactivity of the rabbit-derived ATG with the anti-rabbit antibody used in the
      ELISA. CONCLUSIONS: Assumed HSP70 expression detected such ELISA has to be
      regarded carefully after ATG application. Neither radiochemotherapy, nor
      inflammation or sepsis during aplasia induced HSP70 release into the serum. Thus,
      soluble HSP70 may not be involved in the pathogenesis of acute GvHD.

PMID- 27020765
TI  - The effects of enteral immunonutrition in upper gastrointestinal surgery: A
      systematic review and meta-analysis.
AB  - AIM: The beneficial of immunonutrition on overall morbidity and mortality remains
      uncertain. We undertook a systematic review to evaluate the effects of immune
      enhancing enteral nutrition (IEN) in upper gastrointestinal (GI) surgery.
      METHODS: Main electronic databases [MEDLINE via Pubmed, EMBASE, Scopus, Web of
      Knowledge, Cochrane Central Register of Controlled Trials (CENTRAL) and the
      Cochrane Library, and clinical trial registry (ClinicalTrial.gov)] were searched
      for studies reported clinical outcomes comparing standard enteral nutrition (SEN)
      and immunonutrition (IEN). The systematic review was conducted in accordance with
      the PRISMA guidelines and meta-analysis was analysed using fixed and random
      effects models. RESULTS: Nineteen RCTs with a total of 2016 patients (1017 IEN
      and 999 SEN) were included in the final pooled analysis. The ratio of patients
      underwent oesophagectomy:gastrectomy:pancreatectomy was 2.2:1.2:1.0. IEN, when
      administered post-operatively, was associated with a significantly lower risk of
      wound infection (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.40 to 0.88;
      p = 0.009) and shorter length of hospital stay (MD -2.92 days, 95% CI -3.89 to 
      1.95; p < 0.00001). No significant differences in other post-operative
      morbidities of interest (e.g. anastomotic leak and pulmonary infection) and
      mortality between the two groups were identified. CONCLUSIONS: Overall, our
      analysis found that IEN decreases wound infection rates and reduces length of
      stay. It should be recommended as routine nutritional support as part of the
      Enhanced Recovery after Surgery (ERAS) programmes for upper GI Surgery.

PMID- 27020766
TI  - Risk assessment, risk management and risk-based monitoring following a reported
      accidental release of poliovirus in Belgium, September to November 2014.
AB  - On 6 September 2014, the accidental release of 10(13) infectious wild poliovirus
      type 3 (WPV3) particles by a vaccine production plant in Belgium was reported.
      WPV3 was released into the sewage system and discharged directly to a wastewater
      treatment plant (WWTP) and subsequently into rivers that flowed to the Western
      Scheldt and the North Sea. No poliovirus was detected in samples from the WWTP,
      surface waters, mussels or sewage from the Netherlands. Quantitative microbial
      risk assessment (QMRA) showed that the infection risks resulting from swimming in
      Belgium waters were above 50% for several days and that the infection risk by
      consuming shellfish harvested in the eastern part of the Western Scheldt
      warranted a shellfish cooking advice. We conclude that the reported release of
      WPV3 has neither resulted in detectable levels of poliovirus in any of the
      samples nor in poliovirus circulation in the Netherlands. This QMRA showed that
      relevant data on water flows were not readily available and that prior
      assumptions on dilution factors were overestimated. A QMRA should have been
      performed by all vaccine production facilities before starting up large-scale
      culture of WPV to be able to implement effective interventions when an accident
      happens.

PMID- 27020767
TI  - Electronic origins of photocatalytic activity in d0 metal organic frameworks.
AB  - Metal-organic frameworks (MOFs) containing d(0) metals such as NH2-MIL-125(Ti),
      NH2-UiO-66(Zr) and NH2-UiO-66(Hf) are among the most studied MOFs for
      photocatalytic applications. Despite structural similarities, we demonstrate that
      the electronic properties of these MOFs are markedly different. As revealed by
      quantum chemistry, EPR measurements and transient absorption spectroscopy, the
      highest occupied and lowest unoccupied orbitals of NH2-MIL-125(Ti) promote a long
      lived ligand-to-metal charge transfer upon photoexcitation, making this material
      suitable for photocatalytic applications. In contrast, in case of UiO materials,
      the d-orbitals of Zr and Hf, are too low in binding energy and thus cannot
      overlap with the pi* orbital of the ligand, making both frontier orbitals
      localized at the organic linker. This electronic reconfiguration results in short
      exciton lifetimes and diminishes photocatalytic performance. These results
      highlight the importance of orbital contributions at the band edges and delineate
      future directions in the development of photo-active hybrid solids. 

PMID- 27020769
TI  - Procalcitonin concentrations as a predictor of unexpected readmission and
      mortality after intensive care unit discharge: A retrospective cohort study.
AB  - Procalcitonin (PCT) has been used to guide treatment in critically ill patients
      with sepsis, but whether PCT at intensive care unit (ICU) discharge can stratify
      risks of post-ICU readmission or mortality is unknown. This cohort study compared
      the ability of PCT with C-reactive protein (CRP) in predicting unexpected adverse
      post-ICU events. Of the 1877 patients admitted to the multidisciplinary ICU
      between 1 April 2012 and 31 March 2014, 1653 (88.1%) were discharged without
      treatment limitations. A total of 71 (4.3%) were readmitted and 18 patients (1%)
      died unexpectedly after ICU discharge during the same hospitalization. Both PCT
      (0.6 vs 0.4 MUg/L, P = .002) and a high CRP concentration >100 mg/L (58% vs 41%,
      P = .004) at ICU discharge were associated with an increased risk of adverse post
      ICU events in the univariate analyses; however, the ability of PCT to
      discriminate between patients with and without adverse post-ICU outcomes was
      limited (area under the receiver operating characteristic curve = 0.61; 95%
      confidence interval, 0.55-0.66). In the multivariable analysis, only a high CRP
      concentration (odds ratio, 1.92; 95% confidence interval, 1.12-3.11; P = .008)
      was associated with an increased adverse post-ICU events. Elevated PCT
      concentration at ICU discharge was inadequate in its predictive ability to guide
      ICU discharge.

PMID- 27020768
TI  - The Role of a Catechol-O-Methyltransferase (COMT) Val158Met Genetic Polymorphism
      in Schizophrenia: A Systematic Review and Updated Meta-analysis on 32,816
      Subjects.
AB  - An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680)
      polymorphism and schizophrenia has been reported in the literature, although no
      conclusive outcomes have been attained. The aim of this study was to evaluate the
      association of the COMT Val108/158Met polymorphism with schizophrenia in a
      systematic review and meta-analysis. We performed a keyword search on PubMed and
      EBSCO databases. All English language case-control studies published up to April
      2015 were selected. A total of 67 studies were selected for inclusion. The
      genotype distribution of subjects with schizophrenia was compared with healthy
      control subjects, using allelic, additive, dominant and recessive models. The
      pooled results from the meta-analysis (15,565 cases and 17,251 healthy subjects)
      after the elimination of heterogeneity showed an association between COMT
      Val108/158Met and schizophrenia [recessive model: OR 1.08 CI 95 % (1.01-1.15)].
      We conducted subgroup analyses according to ethnicity. An association was
      observed in our Caucasian population in the additive model [OR 1.21 CI 95 % (1.06
      1.37)] and in the recessive model [OR 1.21 CI 95 % (1.11-1.32)], but not in the
      allelic or dominant models. However, when we analysed our Asian population after
      the elimination of heterogeneity, no evidence of a significant association was
      found in any of the genetic models. Our analyses indicate that there is an
      association between COMT Val108/158Met and schizophrenia in the general
      population. Furthermore, in Caucasian populations, this risk could be increased. 

PMID- 27020770
TI  - Characteristics and outcomes of patients treated with airway pressure release
      ventilation for acute respiratory distress syndrome: A retrospective
      observational study.
AB  - BACKGROUND: The optimal mode of ventilation in acute respiratory distress
      syndrome (ARDS) remains uncertain. Airway pressure release ventilation (APRV) is
      a recognized treatment for mechanically-ventilated patients with severe
      hypoxaemia. However, contemporary data on its role as a rescue modality in ARDS
      is lacking. The goal of this study was to describe the clinical and physiological
      effects of APRV in patients with established ARDS. METHODS: This retrospective
      observational study was performed in a 23-bed adult intensive care unit in a
      tertiary extracorporeal membrane oxygenation (ECMO) referral centre. Patients
      with ARDS based on Berlin criteria were included through a prospectively
      collected APRV database. Patients receiving APRV for less than six hours were
      excluded. RESULTS: Fifty patients fulfilled the eligibility criteria. Prior to
      APRV initiation, median Murray Lung Injury Score was 3.5 (interquartile range
      (IQR) 2.5-3.9) and PaO2/FiO2 was 99mmHg (IQR 73-137). PaO2/FiO2 significantly
      improved within twenty-four hours post-APRV initiation (ANOVA F(1, 27)=24.34,
      P<.005). Two patients (4%) required intercostal catheter insertion for
      barotrauma. Only one patient (2%) required ECMO after APRV initiation, despite a
      majority (68%) fulfilling previously established criteria for ECMO at baseline.
      Hospital mortality rate was 38%. CONCLUSIONS: In patients with ARDS-related
      refractory hypoxaemia treated with APRV, an early and sustained improvement in
      oxygenation, low incidence of clinically significant barotrauma and progression
      to ECMO was observed. The safety and efficacy of APRV requires further
      consideration.

PMID- 27020771
TI  - Post-conflict slowing after incongruent stimuli: from general to conflict
      specific.
AB  - Encountering a cognitive conflict not only slows current performance, but it can
      also affect subsequent performance, in particular when the conflict is induced
      with bivalent stimuli (i.e., stimuli with relevant features for two different
      tasks) or with incongruent trials (i.e., stimuli with relevant features for two
      response alternatives). The post-conflict slowing following bivalent stimuli,
      called "bivalency effect", affects all subsequent stimuli, irrespective of
      whether the subsequent stimuli share relevant features with the conflict stimuli.
      To date, it is unknown whether the conflict induced by incongruent stimuli
      results in a similar post-conflict slowing. To investigate this, we performed six
      experiments in which participants switched between two tasks. In one task,
      incongruent stimuli appeared occasionally; in the other task, stimuli shared no
      feature with the incongruent trials. The results showed an initial performance
      slowing that affected all tasks after incongruent trials. On further trials,
      however, the slowing only affected the task sharing features with the conflict
      stimuli. Therefore, the post-conflict slowing following incongruent stimuli is
      first general and then becomes conflict-specific across trials. These findings
      are discussed within current task switching and cognitive control accounts.

PMID- 27020772
TI  - Botulinum toxin as a therapeutic agent to prevent relapse in deep bite patients.
AB  - INTRODUCTION: The etiology of deep bite is multifactorial. One of the causes is
      increased muscular activity. This makes the treatment of deep bite malocclusions
      difficult and often results in relapse in many cases. In this work we compared
      patients with surgical orthognathic treatment only and surgical orthognathic
      treatment with additional injections of botulinum toxin after mandibular
      advancement for class II division 2 malocclusion. MATERIAL AND METHODS: This is a
      prospective study. Adult patients were assessed pretreatment (T1), posttreatment
      (T2), and long-term after 1 year (T3). In total, 32 patients (mean age, 30.7
      years; 23 women and 9 men) reached the study end point (T3); 24 patients were
      treated without botulinum toxin and 8 patients received preoperative injections
      of botulinum toxin. RESULTS: Significant differences between both groups were
      observed, with a more stable result for the experimental group treated with
      botulinum toxin. DISCUSSION: In a selective group of adult patients with a class
      II division II incisor relationship and with a class II skeletal base, botulinum
      toxin injections can effectively prevent relapse. This may present an alternative
      to a conventional myotomy.

PMID- 27020773
TI  - Unimpeded permeation of water through biocidal graphene oxide sheets anchored on
      to 3D porous polyolefinic membranes.
AB  - 3D porous membranes were developed by etching one of the phases (here PEO,
      polyethylene oxide) from melt-mixed PE/PEO binary blends. Herein, we have
      systematically discussed the development of these membranes using X-ray micro
      computed tomography. The 3D tomograms of the extruded strands and hot-pressed
      samples revealed a clear picture as to how the morphology develops and coarsens
      over a function of time during post-processing operations like compression
      molding. The coarsening of PE/PEO blends was traced using X-ray micro-computed
      tomography and scanning electron microscopy (SEM) of annealed blends at different
      times. It is now understood from X-ray micro-computed tomography that by the
      addition of a compatibilizer (here lightly maleated PE), a stable morphology can
      be visualized in 3D. In order to anchor biocidal graphene oxide sheets onto these
      3D porous membranes, the PE membranes were chemically modified with acid/ethylene
      diamine treatment to anchor the GO sheets which were further confirmed by Fourier
      transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS)
      and surface Raman mapping. The transport properties through the membrane clearly
      reveal unimpeded permeation of water which suggests that anchoring GO on to the
      membranes does not clog the pores. Antibacterial studies through the direct
      contact of bacteria with GO anchored PE membranes resulted in 99% of bacterial
      inactivation. The possible bacterial inactivation through physical disruption of
      the bacterial cell wall and/or reactive oxygen species (ROS) is discussed herein.
      Thus this study opens new avenues in designing polyolefin based antibacterial 3D
      porous membranes for water purification. 

PMID- 27020774
TI  - Development of Point-of-Care Testing for Disaster-Related Infectious Diseases.
AB  - After disaster, the victims lose their safe lives and are even exposed to nature
      where they could suffer from animal bites and vectors followed by suffering from
      zoonosis or vector-born diseases. Because of the urgent need for rapid and cheap
      diagnosis for infectious diseases after disaster, anonymous questionnaire
      clarified that leptospirosis, dengue, diarrhea, and cholera were recognized as
      common disaster-related infections in the Philippines, while diarrhea and
      pneumonia were more common in Indonesia. It should also be noted that infectious
      disease itself such as tuberculosis associated with acquired immune deficiency
      syndrome in South Africa is a disaster. Thus, the possible occurrence of similar
      situation in Asia should be prevented. We have conducted an international
      collaborative research in the Philippines and Indonesia on dengue virus,
      leptospira and mycobacterium tuberculosis (MTB) infectious diseases. Development
      of point-of-care testing for molecular diagnosis and disease severity was the
      principal purpose of the research. Loop-mediated isothermal amplification assay,
      which does not require a source of electricity, was developed for leptospirosis,
      dengue and MTB and has been proved to be useful where resource is limited. The
      plasma levels of matricellular proteins, including galectin-9 and osteopontin,
      were found to reflect the disease severities in dengue virus and MTB infection,
      probably because matricellular proteins are one of the most functional
      extracellular proteins that are associated with inflammatory edema. The study on
      disaster-related infectious disease facilitates the international cooperation for
      development of point-of-care testing for tropical infectious diseases. 

PMID- 27020775
TI  - Sequence characterization and glycosylation sites identification of donkey milk
      lactoferrin by multiple enzyme digestions and mass spectrometry.
AB  - Lactoferrin, a protein showing an array of biochemical properties, including
      immuno-modulation, iron-binding ability, as well as antioxidant, antibacterial
      and antiviral activities, but which may also represent a potential milk allergen,
      was isolated from donkey milk by ion exchange chromatography. The
      characterization of its primary structure, by means of enzymatic digestions,
      SPITC derivatization of tryptic digest, reversed-phase high performance liquid
      chromatography, electrospray and matrix-assisted laser desorption/ionization mass
      spectrometry, is reported. Our results allowed the almost complete
      characterization of donkey lactoferrin sequence, that, at least for the covered
      sequence, differs from the horse genomic deduced sequence (UniProtKB Acc. Nr.
      O77811) by five point substitutions located at positions 91 (Arg -> His), 328
      (Thr -> Ile/Leu), 466 (Ala -> Gly), 642 (Asn -> Ser) and 668 (Ser -> Ala).
      Analysis of the glycosylated protein showed that glycans in donkey lactoferrin
      are linked to the protein backbone via an amide bond to asparagine residues
      located at the positions 137, 281 and 476.

PMID- 27020776
TI  - Creatine kinase in cell cycle regulation and cancer.
AB  - The phosphocreatine-creatine kinase (CK) shuttle system is increasingly
      recognized as a fundamental mechanism for ATP homeostasis in both excitable and
      non-excitable cells. Many intracellular processes are ATP dependent. Cell
      division is a process requiring a rapid rate of energy turnover. Cell cycle
      regulation is also a key point to understanding the mechanisms underlying cancer
      progression. It has been known for about 40 years that aberrant CK levels are
      associated with various cancers and for over 30 years that CK is involved in
      mitosis regulation. However, the underlying molecular mechanisms have not been
      investigated sufficiently until recently. By maintaining ATP at sites of high
      energy demand, CK can regulate cell cycle progression by affecting the
      intracellular energy status as well as by influencing signaling pathways that are
      essential to activate cell division and cytoskeleton reorganization. Aberrant CK
      levels may impair cell viability under normal or stressed conditions and induce
      cell death. The involvement of CK in cell cycle regulation and cellular energy
      metabolism makes it a potential diagnostic biomarker and therapeutic target in
      cancer. To understand the multiple physiological/pathological functions of CK, it
      is necessary to identify CK-binding partners and regulators including proteins,
      non-coding RNAs and participating endogenous small molecular weight chemical
      compounds. This review will focus on molecular mechanisms of CK in cell cycle
      regulation and cancer progression. It will also discuss the implications of
      recent mechanistic studies, the emerging problems and future challenges of the
      multifunctional enzyme CK.

PMID- 27020777
TI  - Novel bioluminescent binding assays for interaction studies of protein/peptide
      hormones with their receptors.
AB  - Protein/peptide hormones are the largest group of endogenous signaling molecules
      and exert various biological functions by binding to specific cell membrane
      receptors. To study the interactions between these hormones and their receptors,
      quantitative ligand-receptor binding assays have been widely used for decades.
      However, the assays conventionally relied on the use of radioligands, which have
      some major drawbacks and can only be used in laboratories with a radioactive
      material license. We recently developed novel bioluminescent binding assays for
      several protein/peptide hormones using the brightest bioluminescent reporter
      known to date, nanoluciferase (NanoLuc). The NanoLuc reporter can be either
      chemically conjugated to an appropriate position, or genetically fused at one
      terminus, of protein/peptide hormones. Compared to conventional radioligands,
      these bioluminescent ligands have higher sensitivity, better safety, and longer
      shelf lives, and thus, represent a novel class of non-radioactive tracers for
      quantitative receptor binding assays. In the present review, we provide some
      general considerations and specific examples for setting up the bioluminescent
      binding assays. Such techniques can be applied to other protein/peptide hormones
      in future to facilitate their interaction studies with their receptors.

PMID- 27020778
TI  - Proteome-derived peptide library for the elucidation of the cleavage specificity
      of HF3, a snake venom metalloproteinase.
AB  - The Proteomic Identification of Cleavage Sites (PICS) approach was employed for
      profiling the substrate specificity of HF3, a hemorrhagic snake venom
      metalloproteinase (SVMP) from Bothrops jararaca. A tryptic peptide library from
      human plasma was subject to HF3 cleavage and amino acid occurrence for P6 to P6'
      sites was mapped. 71 cleavage sites were detected and revealed a clear preference
      for leucine at P1' position, followed by hydrophobic residues in P2'. PICS
      confirmed existing data on prime site specificity of SVMPs.

PMID- 27020779
TI  - An Assessment of Health Interventions Required to Prevent the Transmission of HIV
      Infection Among Men Having Sex with Men in Bujumbura, Burundi.
AB  - Data regarding HIV among men having sex with men (MSM) in Burundi are scarce. In
      a context where same-sex practices are illegal, national recommendations
      including MSM have been issued in 2012. However, no study has been conducted to
      evaluate MSM's health needs, which would be useful to adapt recommendations and
      implement evidence-based interventions. This study aimed at identifying health
      needs expressed by MSM. A cross-sectional study was conducted in Bujumbura in
      2014, in collaboration with the National Association for HIV positive people and
      AIDS patients. Fifty-one MSM, recruited during HIV prevention activities, self
      completed a questionnaire. A descriptive analysis was conducted. Participants had
      a median age of 23 years, over 60 % declared being a member of an LGBT
      organisation and 76 % lived their homosexuality secretly or discretely. Over the
      last month, 67 % declared having had sex with a man and 32 % with a woman. In the
      previous 6 months, 40 % declared having systematically used a condom during
      sexual intercourse. In terms of health needs, 22 % did not use the services
      offered by HIV providers. Participants expressed needs in terms of prevention
      (access to rapid HIV tests, in a confidential setting, with counselling) and care
      (listening centre, free treatment, confidentiality). Medical expertise and being
      a good listener were the predominant healthcare staff qualities desired by
      participants. Results suggest that Burundian MSM represent an at-risk population,
      with low access to HIV services, in need of a comprehensive approach for HIV
      prevention, with community-based activities (HIV testing, counselling, prevention
      tools), psychological and social support.

PMID- 27020780
TI  - Degradation of quinolone antibiotic, norfloxacin, in aqueous solution using gamma
      ray irradiation.
AB  - This study reports the efficiency of gamma-ray irradiation to degrade quinolone
      antibiotic, norfloxacin, in aqueous solution. Laboratory batch experiments were
      conducted to determine the "pseudo-first" order degradation kinetics of
      norfloxacin in the concentration ranges of 3.4-16.1 mg L(-1) by gamma-ray
      irradiation. The dose constant was found to be dependent on the initial
      concentration of norfloxacin and gamma-ray irradiation dose rate (D r). The
      saturation of norfloxacin sample solutions with N2, air or N2O, and the presence
      of tert-butanol and 2-propanol showed that (*)OH played more crucial role in the
      degradation of norfloxacin. The second order rate constants of (*)OH, eaq (-),
      and (*)H with norfloxacin were calculated to be 8.81 * 10(9), 9.54 * 10(8), and
      1.10 * 10(9) M(-1) s(-1), respectively. The effects of various additives
      including CO3 (2-), HCO3 (-), NO3 (-), NO2 (-), and thiourea and the pH of the
      medium on the degradation of norfloxacin were also investigated. Norfloxacin
      degradation was lower in surface water and wastewater than in ultrapure water.
      Several degradation byproducts of norfloxacin were identified from which the
      possible degradation pathway was proposed. 

PMID- 27020781
TI  - Simultaneous open reduction and internal fixation and total hip arthroplasty for
      the treatment of osteoporotic acetabular fractures.
AB  - INTRODUCTION: Surgical treatment of acetabular fractures in elderly people is
      challenging. The main aim of this study is to evaluate retrospectively the
      indications, results and the complications of simultaneous open reduction and
      internal fixation (ORIF) and acute total hip replacement (THR) in the management
      of displaced acetabular fractures. METHODS: This study was performed in an
      academic level I trauma centre. From January 2011 to December 2014, a consecutive
      series of 18 patients (eight females), with average age of 66 years (range 35-81
      years) who had displaced acetabular fractures were included in our study. All
      patients underwent ORIF and simultaneous acute THR. The average duration of
      follow up was 21.7 months (range 12-36 months). RESULTS: At the latest follow up,
      all patients could walk independently. Thirteen patients (72.7 %) had excellent
      Harris hip scores HHS, five, patients (27.7 %) had good results. All fractures
      were healed and the acetabular autologous bone grafts were well incorporated.
      There were no delayed unions or non-unions. Two patients (11 %) had heterotropic
      bone formation which did not affect the activity of the patients. There were no
      signs of loosening of the acetabular cups however one patient had 2 mm medial
      migration of the cup. No vertical migration was observed, and there were no signs
      of loosening around the femoral stem. CONCLUSION: ORIF and simultaneous THR is a
      good option for the treatment of certain types of acetabular fractures
      particularly in elderly population.

PMID- 27020782
TI  - Hamstring graft bacterial contamination during anterior cruciate ligament
      reconstruction: clinical and microbiological study.
AB  - PURPOSE: Autograft preparation for anterior cruciate ligament (ACL)
      reconstruction has a potential for graft contamination. The purpose of this study
      was to evaluate the possibility of bacterial contamination of hamstring autograft
      during preparation and when dropped onto the operating room floor and methods of
      graft decontamination. METHODS: Sixty hamstring tendon autograft specimens were
      used as the test group. Excess tendon not used in the ACL procedure was divided
      into five segments. One segment, at the completion of preparation, was sent for
      culture as a control; the remaining four segments were dropped onto the floor
      adjacent to the surgical field for 15 seconds. One segment was cultured without
      undergoing any further treatment. Cultures were taken from each segment after
      immersion in 10 % povidone-iodine solution, 4 % chlorhexidine and bacitracin,
      respectively, for three minutes. Cultures of a skin swab and floor swab were
      taken at the same time and place that the ACL was dropped. RESULTS: Cultures of
      control graft tissue from ten patients (16.7 %) were positive for bacteria. No
      patient developed post-operative infection. Ninety organisms were identified,
      with Staphylococcus epidermidis being the most common isolate. Grafts rinsed in
      either bacitracin or 4 % chlorhexidine solutions were less likely to be culture
      positive. CONCLUSIONS: A high rate of contamination can be expected during
      autograft preparation for ACL reconstruction. Soaking the hamstring autograft in
      either bacitracin or 4 % chlorhexidine solution is effective for decontamination,
      particulary if graft is dropped on the floor.

PMID- 27020783
TI  - Total knee replacement with tibial tubercle osteotomy in rheumatoid patients with
      stiff knee.
AB  - PURPOSE: Total knee arthroplasty (TKA) is a well-proven modality that can provide
      pain relief and restore mobility for rheumatoid arthritis (RA) patients with
      advanced joint destruction. Patellar ligament avulsion, especially in presence of
      poor bone quality and knee stiffness, is one of the special considerations that
      must be addressed in this unique population of patients. This study aimed to
      determine the functional results in a series of rheumatoid patients with stiff
      knee and end-stage joint destruction who underwent tibial tubercle osteotomy
      during TKA. METHODS: Twenty-three knees in 20 patients (16 women; four men) at a
      mean age of 54 years with end-stage arthritis and knee stiffness due to RA were
      operated upon for TKA using tibial tubercle osteotomy as a step during the
      operation. Patients were reviewed clinically and radiographically with a minimum
      follow-up of two years. Complications were noted. Hospital for Special Surgery
      (HSS) score was recorded pre-operatively and at six and 12 months
      postoperatively. RESULTS: Union occurred at the osteotomy site in 21 of 23 cases.
      One case had deep venous thrombosis (DVT). There was no infection or
      periprosthetic fracture, and at last follow-up, no patient required revision. HSS
      score improved from 46 (15-60) pre-operatively to 85 (71-96) post-operatively.
      CONCLUSION: Tibial tubercle osteotomy during TKA in patients with RA and stiff
      knee is technically demanding yet proved to be effective in improving post
      operative range of movement and minimising the complication of patellar ligament
      avulsion.

PMID- 27020784
TI  - Effects of prazosin and doxazosin on yohimbine-induced reinstatement of alcohol
      seeking in rats.
AB  - RATIONALE AND OBJECTIVES: Alpha-1 adrenoceptor antagonists, such as prazosin,
      show promise in treating alcoholism. In rats, prazosin reduces alcohol self
      administration and relapse induced by footshock stress and the alpha-2 antagonist
      yohimbine, but the processes involved in these effects of prazosin are not known.
      Here, we present studies on the central mechanisms underlying the effects of
      prazosin on yohimbine-induced reinstatement of alcohol seeking. METHODS: In
      experiment 1, we trained rats to self-administer alcohol (12 % w/v, 1 h/day),
      extinguished their responding, and tested the effects of prazosin, administered
      ICV (2 and 6 nmol) or systemically (1 mg/kg) on yohimbine (1.25 mg/kg)-induced
      reinstatement. In experiment 2, we determined potential central sites of action
      by analyzing effects of prazosin (1 mg/kg) on yohimbine (1.25 mg/kg)-induced Fos
      expression. In experiment 3, we determined the effects of doxazosin (1.25, 2.5,
      and 5 mg/kg), an alpha-1 antagonist with a longer half-life on yohimbine-induced
      reinstatement. RESULTS: Yohimbine-induced reinstatement of alcohol seeking was
      reduced significantly by ICV and systemic prazosin (50 and 69 % decreases,
      respectively). Systemic prazosin reduced yohimbine-induced Fos expression in the
      prefrontal cortex, accumbens shell, ventral bed nucleus of the stria terminalis,
      and basolateral amygdala (46-67 % decreases). Doxazosin reduced yohimbine-induced
      reinstatement of alcohol seeking (78 % decrease). CONCLUSIONS: Prazosin acts
      centrally to reduce yohimbine-induced alcohol seeking. The Fos mapping study
      suggests candidate sites where it may act. Doxazosin is also effective in
      reducing yohimbine-induced reinstatement. These data provide information on the
      mechanisms of alpha-1 antagonists on yohimbine-induced alcohol seeking and
      indicate their further investigation for the treatment of alcoholism.

PMID- 27020785
TI  - Enduring abolishment of remote but not recent expression of conditioned fear by
      the blockade of calcium-permeable AMPA receptors before extinction training.
AB  - RATIONALE: Calcium-permeable (GluA2 subunit-free) AMPA receptors (CP-AMPAR) play
      prominent roles in fear extinction; however, no blockers of these receptors were
      studied in tests relevant to extinction learning so far. METHODS: The CP-AMPAR
      antagonist IEM-1460 was administered once before extinction trainings, which were
      started either 1 or 28 days after fear conditioning (FC). We used a mild
      extinction protocol that durably decreased but did not abolish conditioned fear.
      The messenger RNA (mRNA) expression of GluA1 and GluA2 subunits were investigated
      at both time points in the ventromedial prefrontal cortex (vmPFC) and amygdala.
      RESULTS: IEM-1460 transiently facilitated extinction 1 day after conditioning,
      but learned fear spontaneously recovered 4 weeks later. When the extinction
      protocol was applied 28 days after training, IEM-1460 enhanced extinction memory,
      moreover abolished conditioned fear for at least a month. The expression of GluA1
      and GluA2 mRNAs was increased at both time points in the vmPFC. In the
      basolateral and central amygdala, the GluA1/GluA2 mRNA ratio increased,
      suggesting a shift towards the preponderance of GluA1 over GluA2 expression.
      CONCLUSIONS: AMPAR blockade lastingly enhanced the extinction of remote but not
      recent fear memories. Time-dependent changes in AMPA receptor subunit mRNA
      expression may explain the differential effects of CP-AMPAR blockade on recent
      and remote conditioned fear, further supporting the notion that the mechanisms
      maintaining learned fear change over time. Our findings suggest clinical
      implications for CP-AMPAR blockers, particularly for acquired anxieties (e.g.,
      post-traumatic stress disorder) which have a slow onset and are durable.

PMID- 27020786
TI  - The ketamine-like compound methoxetamine substitutes for ketamine in the self
      administration paradigm and enhances mesolimbic dopaminergic transmission.
AB  - RATIONALE: Recently, an increasing number of emergency cases due to a novel
      ketamine-like drug, methoxetamine (MXE), were reported in several countries.
      However, very little is known about the neuropsychopharmacological and
      reinforcing profile of this compound. OBJECTIVES: Our study aims to investigate
      the effects of MXE on self-administration (SA) behaviour in comparison to
      ketamine and on dopaminergic transmission. METHODS: A SA substitution study was
      performed in male rats trained to intravenously (IV) self-administer ketamine. At
      responding stability, rats were exposed to sequential phases of MXE substitution
      at different dosages (starting from 0.5 and then decreasing to 0.25 and 0.125
      mg/kg). Standard electrophysiological techniques were used to record changes in
      firing activities of ventral tegmental area (VTA) dopamine neurons projecting to
      the nucleus accumbens (NAc) shell after acute injection of cumulative doses of
      MXE (0.031-0.5 mg/kg IV). Finally, in vivo microdialysis was performed in freely
      moving rats to evaluate the effect of acute MXE administration (0.125, 0.25 and
      0.5 mg/kg IV) on dopamine release in the NAc shell. RESULTS: MXE 0.125 and 0.25
      mg/kg, but not 0.5 mg/kg, substituted for ketamine SA. MXE also induced a dose
      dependent stimulation of firing rate (p < 0.0001) and burst firing (p < 0.05) of
      NAc-projecting VTA dopamine neurons. Consistently, MXE significantly (p < 0.05)
      increased dopamine extracellular levels in the NAc shell at 0.5 and 0.25 mg/kg
      with different time onsets, i.e. at 40 and 100 min, respectively. CONCLUSIONS:
      This study, while confirming the reinforcing effects of MXE, highlights an
      electrophysiological and neurochemical profile predictive of its addictive
      properties.

PMID- 27020788
TI  - Laser power dependence of mechanoluminescence in metals.
AB  - Mechanoluminescence (ML) glow is produced on the back side when the front of a
      metal sample is irradiated with infrared Nd:YAG laser pulses. An incident laser
      beam with a power density below the plasma-flare onset threshold causes a rise in
      temperature in the studied metal. As the incident laser power density increases,
      the intensity of the ML glow signal also increases. On the basis of the laser
      power density-induced temperature, an expression is derived for the temperature
      induced thermal stress. An expression is derived for the correlation between
      thermal stress and laser power density, which indicates that the temperature
      induced thermal stress is directly related to the incident laser power density.
      In the region of plastic deformation, temperature-induced thermal stress is
      related to the strain and, consequently, to the emitted ML intensity. Finally, an
      expression is derived for the laser power dependence of the ML intensity, and
      good agreement is found between the theoretical and experimental results.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27020787
TI  - The role of carbon monoxide on the anti-nociceptive effects and expression of
      cannabinoid 2 receptors during painful diabetic neuropathy in mice.
AB  - RATIONALE: The activation of cannabinoid 2 receptors (CB2R) attenuates chronic
      pain, but the role played by carbon monoxide synthesized by the inducible heme
      oxygenase 1 (HO-1) on the anti-nociceptive effects produced by a selective CB2R
      agonist, JWH-015, during painful diabetic neuropathy remains unknown. OBJECTIVES
      AND METHODS: In streptozotocin (STZ)-induced diabetic mice, the anti-allodynic
      and anti-hyperalgesic effects of the subcutaneous administration of JWH-015 alone
      or combined with the intraperitoneal administration of a carbon monoxide
      releasing molecule (tricarbonyldichlororuthenium(II) dimer (CORM-2)) or an HO-1
      inducer compound (cobalt protoporphyrin IX (CoPP)) at 10 mg/kg were evaluated.
      Reversion of JWH-015 anti-nociceptive effects by the administration of an HO-1
      inhibitor (tin protoporphyrin IX (SnPP)) and a CB2R antagonist (AM630) was also
      evaluated. Furthermore, the protein levels of HO-1, neuronal nitric oxide
      synthase (NOS1), and CB2R in diabetic mice treated with CORM-2 and CoPP alone or
      combined with JWH-015 were also assessed. RESULTS: The administration of JWH-015
      dose dependently inhibited hypersensitivity induced by diabetes. The effects of
      JWH-015 were enhanced by their coadministration with CORM-2 or CoPP and reversed
      by SnPP or AM630. The increased protein levels of HO-1 induced by CORM-2 and CoPP
      treatments were further enhanced in JWH-015-treated mice. All treatments
      similarly enhanced the peripheral expression of CB2R and avoided the spinal cord
      over-expression of NOS1 induced by diabetes. CONCLUSIONS: The activation of HO-1
      enhanced the anti-nociceptive effects of JWH-015 in diabetic mice, suggesting
      that coadministration of JWH-015 with CORM-2 or CoPP might be an interesting
      approach for the treatment of painful diabetic neuropathy in mice.

PMID- 27020789
TI  - Pharmacokinetics of linezolid in critically ill patients.
AB  - INTRODUCTION: Linezolid is an oxazolidinone antibiotic active against Gram
      positive bacteria, and is most commonly used to treat life-threatening infections
      in critically ill patients. The pharmacokinetics of linezolid are profoundly
      altered in critically ill patients, partly due to decreased function of vital
      organs, and partly because life-sustaining drugs and devices may change the
      extent of its excretion. AREAS COVERED: This article is summarizes key changes in
      the pharmacokinetics of linezolid in critically ill patients. The changes
      summarized are clinically relevant and may serve as rationale for dosing
      recommendations in this particular population. EXPERT OPINION: While absorption
      and penetration of linezolid to tissues are not significantly changed in
      critically ill patients, protein binding of linezolid is decreased, volume of
      distribution increased, and metabolism may be inhibited leading to non-linear
      kinetics of elimination; these changes are responsible for high inter-individual
      variability of linezolid plasma concentrations, which requires therapeutic plasma
      monitoring and choice of continuous venous infusion as the administration method.
      Acute renal or liver failure decrease clearance of linezolid, but renal
      replacement therapy is capable of restoring clearance back to normal, obviating
      the need for dosage adjustment. More population pharmacokinetic studies are
      necessary which will identify and quantify the influence of various factors on
      clearance and plasma concentrations of linezolid in critically ill patients.

PMID- 27020790
TI  - Interstitial 11q24 deletion: a new case and review of the literature.
AB  - We describe a 19-month-old male presenting with right stenotic megaureter, anemia
      and thrombocytopenia, cardiac and ophthalmologic abnormalities. Analysis with
      array-based comparative genomic hybridization (aCGH) revealed an interstitial
      deletion of about 2.4 Mb of chromosome 11q24.2q24.3. We compared the phenotype of
      our patient with that of recently reported patients studied by aCGH, who showed
      an overlapping deletion. We also analysed the gene content of the deleted region
      in order to investigate the possible involvement of specific genes in the
      clinical phenotype. 

PMID- 27020792
TI  - Work-Life Balance, Burnout, and Satisfaction of Early Career Pediatricians.
AB  - BACKGROUND AND OBJECTIVE: Data describing factors associated with work-life
      balance, burnout, and career and life satisfaction for early career pediatricians
      are limited. We sought to identify personal and work factors related to these
      outcomes. METHODS: We analyzed 2013 survey data of pediatricians who graduated
      residency between 2002 and 2004. Dependent variables included: (1) balance
      between personal and professional commitments, (2) current burnout in work, (3)
      career satisfaction, and (4) life satisfaction. Multivariable logistic regression
      examined associations of personal and work characteristics with each of the 4
      dependent variables. RESULTS: A total of 93% of participants completed the survey
      (n = 840). A majority reported career (83%) and life (71%) satisfaction. Fewer
      reported current appropriate work-life balance (43%) or burnout (30%). In
      multivariable modeling, excellent/very good health, having support from physician
      colleagues, and adequate resources for patient care were all found to be
      associated with a lower prevalence of burnout and a higher likelihood of work
      life balance and career and life satisfaction. Having children, race, and
      clinical specialty were not found to be significantly associated with any of the
      4 outcome measures. Female gender was associated with a lower likelihood of
      balance and career satisfaction but did not have an association with burnout or
      life satisfaction. CONCLUSIONS: Burnout and struggles with work-life balance are
      common; dissatisfaction with life and career are a concern for some early career
      pediatricians. Efforts to minimize these outcomes should focus on encouragement
      of modifiable factors, including health supervision, peer support, and ensuring
      sufficient patient care resources.

PMID- 27020791
TI  - Emerging applications of riboswitches - from antibacterial targets to molecular
      tools.
AB  - The ability to precisely regulate gene expression is one of the most important
      features of the living cells as it enables the adaptation and survival in
      different environmental conditions. The majority of regulatory mechanisms involve
      protein action, however, multiple genes are controlled by nucleic acids. Among
      RNA-based regulators, the riboswitches present a large group of specific domains
      within messenger RNAs able to respond to small metabolites, tRNA, secondary
      messengers, ions, vitamins or amino acids. A simple, accurate, and efficient
      mechanism of action as well as easiness in handling and engineering make the
      riboswitches a potent practical tool in industry, medicine, pharmacy or
      environmental protection. Hereby, we summarize the current achievements and
      challenges in designing and practical employment of the riboswitch-based tools.

PMID- 27020793
TI  - Acute Otitis Media and Other Complications of Viral Respiratory Infection.
AB  - BACKGROUND: Viral upper and lower respiratory tract infections (URI, LRI) are
      common in infants. We determined the prevalence of viral URI and its
      complications, including acute otitis media (AOM) and LRI, and assessed the
      effect of bacterial-viral interactions, and genetic and environmental risks on
      AOM development. METHODS: Healthy infants were enrolled from near birth and
      followed to the first episode of AOM up to 12 months of age. Nasopharyngeal
      specimens were collected at monthly intervals (months 1-6, 9) and during viral
      URI episodes for bacterial culture and viral polymerase chain reaction studies.
      Subjects were followed closely for AOM development. RESULTS: A total of 367
      infants were followed for 286 child-years; 887 URI (305 infants) and 180 AOM
      episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the
      first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM
      incidence by ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and
      without AOM had 4.7 and 2.3 URI episodes per child-year, respectively (P < .002).
      Pathogenic bacterial colonization rates by month were significantly higher in
      infants with AOM (P < .005). Breastfeeding reduced both URI and AOM risks (P <
      .05). Significant bacterial-viral interactions occurred with Moraxella
      catarrhalis and a variety of respiratory viruses and altered URI and AOM risks.
      CONCLUSIONS: Almost half of infants experienced AOM by age 1. Important AOM risk
      factors included frequent viral URI, pathogenic bacterial colonization, and lack
      of breastfeeding. Bacterial-viral interactions may play a significant role in AOM
      pathogenesis and deserve further investigation.

PMID- 27020794
TI  - Financing Graduate Medical Education to Meet the Needs of Children and the Future
      Pediatrician Workforce.
AB  - The American Academy of Pediatrics (AAP) believes that an appropriately financed
      graduate medical education (GME) system is critical to ensuring that sufficient
      numbers of trained pediatricians are available to provide optimal health care to
      all children. A shortage of pediatric medical subspecialists and pediatric
      surgical specialists currently exists in the United States, and this shortage is
      likely to intensify because of the growing numbers of children with chronic
      health problems and special health care needs. It is equally important to
      maintain the supply of primary care pediatricians. The AAP, therefore, recommends
      that children's hospital GME positions funded by the Health Resources and
      Services Administration be increased to address this escalating demand for
      pediatric health services. The AAP also recommends that GME funding for pediatric
      physician training provide full financial support for all years of training
      necessary to meet program requirements. In addition, all other entities that gain
      from GME training should participate in its funding in a manner that does not
      influence curriculum, requirements, or outcomes. Furthermore, the AAP supports
      funding for training innovations that improve the health of children. Finally,
      the AAP recommends that all institutional recipients of GME funding allocate
      these funds directly to the settings where training occurs in a transparent
      manner. 

PMID- 27020795
TI  - Reduced arterial stiffness in very fit boys and girls.
AB  - Low cardiorespiratory fitness is associated with higher cardiovascular risk,
      whereas high levels of cardiorespiratory fitness protect the cardiovascular
      system. Carotid intima-media thickness and arterial distensibility are well
      established parameters to identify subclinical cardiovascular disease. Therefore,
      this study investigated the influence of cardiorespiratory fitness and muscular
      strength on carotid intima-media thickness and arterial distensibility in 697
      children and adolescents (376 girls), aged 7-17 years. Cardiorespiratory fitness
      and strength were measured with the test battery FITNESSGRAM; carotid intima
      media thickness, arterial compliance, elastic modulus, stiffness index beta, and
      pulse wave velocity beta were assessed by B- and M-mode ultrasound at the common
      carotid artery. In bivariate correlation, cardiorespiratory fitness was
      significantly associated with all cardiovascular parameters and was an
      independent predictor in multivariate regression analysis. No significant
      associations were obtained for muscular strength. In a one-way variance analysis,
      very fit boys and girls (58 boys and 74 girls>80th percentile for
      cardiorespiratory fitness) had significantly decreased stiffness parameters
      (expressed in standard deviation scores) compared with low fit subjects (71 boys
      and 77 girls<20th percentile for cardiorespiratory fitness): elastic modulus 
      0.16+/-1.02 versus 0.19+/-1.17, p=0.009; stiffness index beta -0.15+/-1.08 versus
      0.16+/-1.1, p=0.03; and pulse wave velocity beta -0.19+/-1.02 versus 0.19+/-1.14,
      p=0.005. Cardiorespiratory fitness was associated with healthier arteries in
      children and adolescents. Comparison of very fit with unfit subjects revealed
      better distensibility parameters in very fit boys and girls.

PMID- 27020796
TI  - Measuring Sustainment of Multiple Practices Fiscally Mandated in Children's
      Mental Health Services.
AB  - Examining sustainment of multiple evidence-based practices is crucial to
      understanding the processes and outcomes of system-driven implementation efforts
      that are increasingly common. This study used administrative claims data to
      characterize volume and penetration of six practices over 19 fiscal quarters
      following initial implementation within the context of a system-driven, fiscally
      mandated implementation effort in Los Angeles County Department of Mental
      Health's Prevention and Early Intervention services. Patterns of volume changes
      over time revealed an overall ramp up of practice claims over time, but
      variability in patterns of volume and penetration for each practice. Findings
      varied by the methods used to index and analyze volume and penetration.
      Furthermore, a number of client case-mix and therapist characteristics were
      associated with the volume of therapists' claims for each practice relative to
      their claims for the other practices.

PMID- 27020797
TI  - Nurses' readiness for evidence-based practice at Finnish university hospitals: a
      national survey.
AB  - AIMS: The aim of this study was to determine nurses' readiness for evidence-based
      practice at Finnish university hospitals. BACKGROUND: Although systematic
      implementation of evidence-based practice is essential to effectively improving
      patient outcomes and value of care, nurses do not consistently use evidence in
      practice. Uptake is hampered by lack of nurses' individual and organizational
      readiness for evidence-based practice. Although nurses' evidence-based practice
      competencies have been widely studied in countries leading the evidence-based
      practice movement, less is known about nurses' readiness for evidence-based
      practice in the non-English-speaking world. DESIGN: A cross-sectional descriptive
      survey design. METHODS: The study was conducted in November-December 2014 in
      every university hospital in Finland with a convenience sample (n = 943) of
      practicing nurses. The electronic survey data were collected using the Stevens'
      Evidence-Based Practice Readiness Inventory, which was translated into Finnish
      according to standardized guidelines for translation of research instruments. The
      data were analysed using descriptive and inferential statistics. RESULTS: Nurses
      reported low to moderate levels of self-efficacy and low levels of evidence-based
      practice knowledge. A statistically significant, direct correlation was found
      between nurses' self-efficacy in employing evidence-based practice and their
      actual evidence-based practice knowledge level. Several statistically significant
      differences were found between nurses' socio-demographic variables and nurses'
      self-efficacy in employing evidence-based practice, and actual and perceived
      evidence-based practice knowledge. CONCLUSIONS: Finnish nurses at university
      hospitals are not ready for evidence-based practice. Although nurses are familiar
      with the concept of evidence-based practice, they lack the evidence-based
      practice knowledge and self-efficacy in employing evidence-based practice
      required for integrating best evidence into clinical care delivery.

PMID- 27020798
TI  - The ictal wavefront is the spatiotemporal source of discharges during spontaneous
      human seizures.
AB  - The extensive distribution and simultaneous termination of seizures across
      cortical areas has led to the hypothesis that seizures are caused by large-scale
      coordinated networks spanning these areas. This view, however, is difficult to
      reconcile with most proposed mechanisms of seizure spread and termination, which
      operate on a cellular scale. We hypothesize that seizures evolve into self
      organized structures wherein a small seizing territory projects high-intensity
      electrical signals over a broad cortical area. Here we investigate human seizures
      on both small and large electrophysiological scales. We show that the migrating
      edge of the seizing territory is the source of travelling waves of synaptic
      activity into adjacent cortical areas. As the seizure progresses, slow dynamics
      in induced activity from these waves indicate a weakening and eventual failure of
      their source. These observations support a parsimonious theory for how large
      scale evolution and termination of seizures are driven from a small, migrating
      cortical area. 

PMID- 27020800
TI  - Degradation mechanism(s) of GaAs solar cells with Cu contacts.
AB  - Substrate-based GaAs solar cells having a dense Au/Cu front contact grid with 45%
      surface coverage were exposed to accelerated life testing at temperatures between
      200 and 300  degrees C. TEM analysis of the front contacts was used to gain a
      better understanding of the degradation process. During accelerated life testing
      at 200  degrees C only intermixing of the Au and Cu in the front contact occurs,
      without any significant influence on the J-V curve of the cells, even after 1320
      h (55 days) of accelerated life testing. At temperatures >=250  degrees C a
      recrystallization process occurs in which the metals of the contact and the GaAs
      front contact layer interact. Once the grainy recrystallized layer starts to
      approach the window, diffusion via grain boundaries to the window and into the
      active region of the solar cells occurs, causing a decrease in Voc due to
      enhanced non-radiative recombination via Cu trap levels introduced in the active
      region of the solar cell. To be a valid simulation of space conditions the
      accelerated life testing temperature should be <250  degrees C in future
      experiments, in order to avoid recrystallization of the metals with the GaAs
      contact layer.

PMID- 27020801
TI  - Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM).
AB  - The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of
      humans. They are normal inhabitants of premise plumbing, found, for example, in
      household and hospital shower heads, water taps, aerators, and hot tubs. The
      hydrophobic NTM are readily aerosolized, and pulmonary infections and
      hypersensitivity pneumonitis have been traced to the presence of NTM in shower
      heads. Hypersensitivity pneumonitis in automotive workers was traced to the
      presence of NTM in metal recovery fluid used in grinding operations. Recently,
      NTM bacteremia in heart transplant patients has been traced to the presence of
      NTM in water reservoirs of instruments employed in operating rooms to heat and
      cool patient blood during periods of mechanical circulation. Although NTM are
      difficult to eradicate from premise plumbing as a consequence of their
      disinfectant-resistance and formation of biofilms, measures such as reduction of
      turbidity and reduction in carbon and nitrogen for growth and the installation of
      microbiological filters can reduce exposure of NTM to susceptible individuals. 

PMID- 27020802
TI  - Correlates of Anxiety in 6- to 8-Year-Old Children With ADHD: A Community-Based
      Study.
AB  - OBJECTIVE: The aim of this study was to identify the child and parent/family
      correlates of anxiety in a community-based sample of children with ADHD. METHOD:
      Children (6-8 years) with ADHD ( n = 179) and controls ( n = 212) were assessed
      for ADHD and anxiety using the Diagnostic Interview Schedule for Children IV.
      Potential child and parent/family correlates were measured through direct
      assessments, and parent- and teacher-reported questionnaires. Associations were
      examined using univariate and multivariate logistic regression analyses. RESULTS:
      One in four children with ADHD ( n = 44) met criteria for an anxiety disorder,
      compared with one in 20 controls ( n = 10). Anxiety was common in both boys and
      girls with ADHD. The strongest correlates of anxiety in multivariate analyses
      were ADHD subtype, primary caregiver psychosocial distress, and neighborhood
      socioeconomic disadvantage. CONCLUSION: Anxiety is common in children with ADHD.
      This study provides insight into the potential parent/family stressors that may
      increase risk for anxiety in children with ADHD.

PMID- 27020799
TI  - Neuropeptide diversity and the regulation of social behavior in New World
      primates.
AB  - Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that
      regulate peripheral physiology, and have emerged as important modulators of brain
      function, particularly in the social realm. OT structure and the genes that
      ultimately determine structure are highly conserved among diverse eutherian
      mammals, but recent discoveries have identified surprising variability in OT and
      peptide structure in New World monkeys (NWM), with five new OT variants
      identified to date. This review explores these new findings in light of
      comparative OT/AVP ligand evolution, documents coevolutionary changes in the
      oxytocin and vasopressin receptors (OTR and V1aR), and highlights the
      distribution of neuropeptidergic neurons and receptors in the primate brain.
      Finally, the behavioral consequences of OT and AVP in regulating NWM sociality
      are summarized, demonstrating important neuromodulatory effects of these
      compounds and OT ligand-specific influences in certain social domains.

PMID- 27020803
TI  - Reproductive and population parameters of spiny dogfish Squalus acanthias in the
      south-western Atlantic Ocean.
AB  - The objective of this study was to estimate reproductive and population
      parameters of the spiny dogfish Squalus acanthias for the south-western Atlantic
      Ocean. In total, 2714 specimens (1616 males and 1098 females) were collected from
      surveys carried out using research vessels. Males ranged from 225 to 861 mm total
      length (LT ) and females from 235 to 925 mm LT . The size at maturity of females
      (651 mm) was significantly greater than that of males (565 mm). The maximum
      proportion of mature individuals (Pmax ) of the gestation ogive was <1, which
      indicates that a proportion of mature females was not in gestation. This
      inactivity may be explained by the occurrence of resting periods between cycles
      or by the asynchrony of the reproductive cycle. The estimated Pmax for the
      maternity ogive suggested that about one third of mature females were in the
      maternity stage (i.e. with embryos >156 mm). The temporal and spatial co
      occurrence of non-gravid adult females at different stages of ovarian
      development, as well as gravid females at all embryonic development stages would
      indicate that the female reproductive cycle in the south-western Atlantic Ocean
      is asynchronous. The results indicate that S. acanthias is susceptible to fishing
      pressure on account of its length at maturity, extended reproductive cycles and
      low fecundity. 

PMID- 27020804
TI  - Patient perspectives on antibiotics for appendicitis at one hospital.
AB  - BACKGROUND: Appendicitis has long been considered a progressive inflammatory
      condition best treated by prompt appendectomy. Recently, several trials comparing
      initial treatment with antibiotics alone to appendectomy suggest that antibiotic
      therapy may be a safe option in select patients. However, little is known about
      patients' understanding of appendicitis, prioritized outcomes, and treatment
      preferences. MATERIALS AND METHODS: We conducted a prospective, observational
      survey at a Los Angeles County public hospital emergency department. Trained
      study coordinators recorded the following data on each subject: basic knowledge
      of appendicitis, past surgical and antibiotic history, and medical illness
      outcome priorities. Participants were then educated about appendicitis and were
      told that studies had demonstrated that appendicitis can be treated safely with
      antibiotics alone. Subjects were then surveyed as to their preference for urgent
      surgery or antibiotics alone in a hypothetical scenario of acute uncomplicated
      appendicitis. RESULTS: Of 129 subjects interviewed, 56 (43%) correctly defined
      appendicitis, and 69 (53%) identified the treatment for appendicitis as surgery.
      When presented with a hypothetical acute appendicitis scenario, 57% chose
      antibiotics over surgery. Persons with previous appendectomy and parents of
      minors more often chose antibiotics alone, 74% and 63%, respectively. Dying was
      the most frequently cited and highest-ranked concern about medical illness.
      CONCLUSIONS: Our results demonstrate that, among persons at one US public
      hospital, understanding of appendicitis is poor. Once presented with background
      information about appendicitis and being informed that antibiotics can safely
      treat appendicitis, many people would prefer an antibiotic approach over
      appendectomy. Death is the most prioritized concern.

PMID- 27020805
TI  - Alpha7 nicotinic acetylcholine receptor activation attenuated intestine-derived
      acute lung injury.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (IIR) could lead to acute lung
      injury, associated with severe alveolar epithelial cells inflammatory and
      oxidative injury. Alpha7 nicotinic acetylcholine receptor (alpha7nAChR) is an
      essential component of the cholinergic anti-inflammatory pathway. The aim of this
      study was to investigate the important role of alpha7nAChR on the lung subjected
      to IIR. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four
      groups (n = 8 in each): sham group (group S), model group (group M), alpha7nAChR
      agonist PNU-282987-treated group (group PNU), and specific alpha7nAChR antagonist
      methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by
      clamping the superior mesenteric artery for 75 min, followed by a 120-min
      reperfusion. All rats were killed at 2 h after release of the clamps. The
      histologic examination of lungs was made, and lung water content was detected.
      Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6,
      and superoxide dismutase activity of the lungs were detected. Additionally,
      expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF
      kappaB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl
      2, and cleaved-caspase3) were detected using Western blot. RESULTS: Lungs were
      damaged after intestine IR, manifested by higher lung water content, histologic
      score, concentrations of interleukin-6, tumor necrosis factor alpha, and
      malondialdehyde of group M than those of group S, accompanied with decreased
      superoxide dismutase activity (P < 0.05). PNU treatment could significantly
      improve the pulmonary function of rats subjected to IIR. These effects of
      activation of alpha7nAChR were associated with suppression of TLR4/NF-kappaB
      pathway and subsequent reduction of apoptosis-related protein. However, MLA
      treatment aggravated lung injury. CONCLUSIONS: alpha7nAChR plays a role in acute
      lung injury induced by IIR via attenuating lung oxidative stress and inflammation
      through suppression of TLR4/NF-kappaB pathway, resulting in reduction of
      apoptosis in the lung.

PMID- 27020806
TI  - Impact of American College of Surgeons Oncology Group Z11 on surgical training at
      an academic cancer center.
AB  - BACKGROUND: The application of the American College of Surgeons Oncology Group
      Z0011 trial (Z11) has resulted in fewer completion axillary lymph node
      dissections (ALNDs) for select patients. We hypothesize that the application of
      Z11 may result in fewer ALND cases for surgeons in training. METHODS: In the
      setting of an academic cancer center incorporating Z11 into routine practice, we
      compared the total number of ALND performed in a pre-Z11 period (January 2007
      April 2011, 52 mo) and post-Z11 period (April 2011-February 2014, 34 mo). We also
      identified the number of patients in the post-Z11 era in whom ALND was omitted as
      a result of Z11. Clinical and pathologic characteristics among these groups were
      analyzed. RESULTS: A total of 279 and 191 ALNDs were performed in the pre-Z11 and
      post-Z11 groups, respectively. Variables were similar among these groups with
      respect to demographics, tumor characteristics, and surgeries performed. There
      was no difference in the monthly rates of ALND between groups-5.37 cases/mo (pre
      Z11) and 5.62 cases/mo (post-Z11), P = 0.52. We identified a total of 53 patients
      for whom ALND was omitted due to Z11 application in the post-Z11 period,
      representing a potential 21.7% decrease (53/191 + 53) in the number of ALNDs in
      this period. CONCLUSIONS: Although the application of Z11 could potentially
      impact surgical training with a 21.7% decrease in ALND cases (53/191 + 53), the
      surgical case volume at an academic cancer center absorbs this decrease and
      maintains consistent levels of training for ALND.

PMID- 27020807
TI  - Role of atrial natriuretic peptide in ischemic preconditioning-induced
      cardioprotection in the diabetic rat heart.
AB  - BACKGROUND: It has been noted that nitric oxide (NO) is involved in the ischemic
      preconditioning (IPC)-mediated cardioprotection. Diabetes is a downregulator of
      atrial natriuretic peptide (ANP), resulting in low expression of endothelial
      nitric oxide synthase (eNOS) by which NO level get reduced. The purpose of the
      present study was to investigate the role of ANP in attenuated cardioprotective
      effect of IPC in the diabetic rat heart. METHODS: The heart was isolated from the
      diabetic rat and mounted on Langendorff's apparatus, subjected to 30-min ischemia
      and 120-min reperfusion. IPC was mediated by four cycles of 5-min ischemia and 5
      min reperfusion. The infarct size was estimated using triphenyltetrazolium
      chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and
      creatinine kinase-MB release to assess the degree of myocardial injury. The
      cardiac release of NO was estimated indirectly by measuring the release of
      nitrite in coronary effluent. RESULTS: IPC-mediated cardioprotection was
      significantly attenuated in the diabetic rat as compared with the normal rat.
      Perfusion of ANP (0.1 MUM/L) in the diabetic rat heart significantly restored the
      attenuated cardioprotective effect of IPC and also increased the release of NO.
      However, this observed cardioprotection was significantly attenuated by perfusion
      of N-nitro L-arginine methyl ester, an eNOS inhibitor (100 MUM/L) noted in terms
      of increase in myocardial infarct size, release of lactate dehydrogenase and
      creatinine kinase-MB, and also decreases in release of NO. CONCLUSIONS: Thus, it
      is suggested that ANP restores the attenuated cardioprotective effect in the
      diabetic heart which may be due to increase in the expression of eNOS and
      subsequent increase in the activity of NO.

PMID- 27020808
TI  - Independent risk factors for prolonged postoperative ileus development.
AB  - BACKGROUND: Postoperative ileus (POI) has a significant impact on patient
      wellbeing, and with a 15% incidence in colectomy patients costs US hospitals
      >$1.3 billion per year. Although some causative mechanisms have been identified,
      little is known about what places patients at risk for ileus. We aimed to
      identify factors that independently influence the development of POI. MATERIALS
      AND METHODS: Patients who underwent elective surgery between 2011 and 2012 were
      identified from the colectomy-specific American College of Surgeons National
      Surgical Quality Improvement Program database. Descriptive statistics were
      calculated, and demographics, comorbidities, preoperative treatments, and
      operative characteristics were evaluated as risk factors using multivariate
      analyses. RESULTS: A total of 9734 patients were included in this analysis; 1364
      (14%) were found to have POI. Patients who developed an ileus were more likely to
      develop any postoperative complication, to be readmitted, and require reoperation
      compared with patients without POI. In addition, we identified 13 independent
      risk factors for POI. CONCLUSIONS: Five modifiable risk factors for development
      of POI were identified as follows: smoking, weight loss, preoperative oral
      antibiotics, mechanical bowel preparation, and surgical approach. These
      identifications provide insight into possible targets for preoperative
      modification, which may lead to improvements in patients' quality of life and
      influence outcomes such as postoperative complications, readmission, and
      reoperation.

PMID- 27020809
TI  - Pericardium matrix buttressing hinders the stapled bronchial stump healing.
AB  - BACKGROUND: Biomechanical and histological properties of stapled bronchi with and
      without bovine pericardial matrix plus collagen reinforcement are analyzed.
      MATERIALS AND METHODS: Pneumonectomy with mechanical bronchial suture was
      performed in the swine model. Pigs were randomly assigned to three groups: three
      row staplers without reinforcement (Traditional), with reinforcement (Buttressed)
      and control "wild type", non-resected normal bronchus (Normal). Intraoperative
      test was carried for air leaks at 20/30/40 mm Hg endobronchial pressure. After 60
      d, tracheobronchial specimen was harvested, stocked, and analyzed. Tensile test
      was performed using INSTRON 5965 loading frame machine. Maximal strain resistance
      value, length of elongation at rupture parameter, and stiffness coefficient (K)
      were evaluated. Histological analysis was performed. Sample size calculation was
      assessed (four per group), and the Student t-test was used to statistically
      evaluate differences in biomechanical variables. RESULTS: No fistula occurred.
      Biomechanical analysis showed that maximal strain resistance is 41.22 +/- 2.11 N
      (Traditional), 24.53 +/- 3.47 N (Buttressed), and 30.91 +/- 0.29 N (Normal);
      elongation at rupture is 16.01 +/- 1.82 mm (Traditional), 12.89 +/- 0.48 mm
      (Buttressed), and 9.32 +/- 0.11 mm (Normal). Finally, K is 2.59 +/- 0.16 N/mm
      (Traditional), 1.91 +/- 0.33 N/mm (Buttressed), and 3.32 +/- 0.01 N/mm (Normal).
      Stumps without reinforcement proved higher resistance and length of elongation
      than reinforced ones. Normal bronchial tissue shows the highest stiffness
      coefficient. Statistical analysis produced significant values for each
      biomechanical feature. Group Buttressed stumps show greater thickness and a
      substantial inflammatory reaction with granulation tissue along the whole scar
      and around areas of discontinuity within the scar, not yet healed. CONCLUSIONS:
      Reinforcing the mechanical suture line of bronchial stump with bovine pericardial
      matrix plus collagen shows suboptimal biomechanical and histological
      characteristics compared to using the stapler alone.

PMID- 27020810
TI  - The use of skin substitutes and burn care-a survey.
AB  - OBJECTIVE: The aim of our Internet survey was to assess the preferences of burn
      specialists who use skin substitutes in patients with burns covering 20% or more
      of their total body surface area (TBSA). METHODS: An open, voluntary Internet
      based cross-sectional survey was performed. Responses to 19 noncompulsory
      questions, and participant career and location information were collected.
      RESULTS: One hundred eleven specialists from 36 countries responded to our
      questionnaire. Sixty participants were located in Europe (54%), followed by 31
      (28%) in North America, 15 (14%) in Asia, three (3%) in South America, one (1%)
      in Africa, and one (1%) in Australia. The importance of skin substitutes in
      medium-sized burns (covering 20%-60% TBSA) was rated as "essential" by 28% and
      "desirable" by 56% of the respondents. In severe burns >60% of TBSA, 81% of
      responders rated the use of skin substitutes as "essential" and 14% as
      "desirable". Skin substitutes were used in daily clinical practice by 96% of all
      participants. Biological and synthetic dressings were used by 53%. A majority
      (86%) think that biological dressings do not pose a risk to patients. Allografts
      represent the most frequently used wound coverage (51%), followed by xenografts
      (28%). All participants of the survey indicated that as of yet, there is no ideal
      skin substitute available. CONCLUSIONS: Split-thickness autografts still
      represent the most used wound cover for definitive treatment of severe burns.
      However, creation and implementation of an ideal skin substitute have yet to be
      achieved and therefore should be the focus of future work.

PMID- 27020811
TI  - Compression therapy affects collagen type balance in hypertrophic scar.
AB  - BACKGROUND: The effects of pressure on hypertrophic scar are poorly understood.
      Decreased extracellular matrix deposition is hypothesized to contribute to
      changes observed after pressure therapy. To examine this further, collagen
      composition was analyzed in a model of pressure therapy in hypertrophic scar.
      MATERIALS AND METHODS: Hypertrophic scars created on red Duroc swine (n = 8)
      received pressure treatment (pressure device mounting and delivery at 30 mm Hg),
      sham treatment (device mounting and no delivery), or no treatment for 2 wk. Scars
      were assessed weekly and biopsied for histology, hydroxyproline quantification,
      and gene expression analysis. Transcription levels of collagen precursors COL1A2
      and COL3A1 were quantified using reverse transcription-polymerase chain reaction.
      Masson trichrome was used for general collagen quantification, whereas
      immunofluorescence was used for collagen types I and III specific quantification.
      RESULTS: Total collagen quantification using hydroxyproline assay showed a 51.9%
      decrease after pressure initiation. Masson trichrome staining showed less
      collagen after 1 (P < 0.03) and 2 wk (P < 0.002) of pressure application compared
      with sham and untreated scars. Collagen 1A2 and 3A1 transcript decreased by 41.9-
      and 42.3-fold, respectively, compared with uninjured skin after pressure
      treatment, whereas a 2.3- and 1.3-fold increase was seen in untreated scars. This
      decrease was seen in immunofluorescence staining for collagen types I (P < 0.001)
      and III (P < 0.04) compared with pretreated levels. Pressure-treated scars also
      had lower levels of collagen I and III after pressure treatment (P < 0.05)
      compared with sham and untreated scars. CONCLUSIONS: These results demonstrate
      the modulation of collagen after pressure therapy and further characterize its
      role in scar formation and therapy.

PMID- 27020812
TI  - Use of simulation to assess a statistically driven surgical scheduling system.
AB  - BACKGROUND: To maximize operating room (OR) utilization, better estimates of case
      duration lengths are needed. We used computerized simulation to determine whether
      scheduling OR cases using a statistically driven system that incorporates patient
      and surgery-specific factors in the process of case duration prediction improves
      OR throughput and utilization. METHODS: We modeled surgical and anesthetic length
      of vascular surgical procedures as a function of patient and operative
      characteristics using a multivariate linear regression approach (Predictive
      Modeling System [PMS]). Mean historical operative time per surgeon (HMS) and mean
      anesthetic time were also calculated for each procedure type. A computerized
      simulation of scheduling in a single OR performing vascular operations was then
      created using either the PMS or the HMS. RESULTS: Compared to HMS, scheduling the
      operating room using the PMS increased throughput by a minimum of 15% (99.8%
      cumulative probability, P < 0.001). The PMS was slightly more likely to lead to
      overtime (mean 13% versus 11% of operative days during a calendar year, P <
      0.001). However, the overtime lasted longer in the HMS group (mean 140 versus 95
      min per day of overtime, P < 0.001). PMS was associated with lower OR
      underutilization rate (mean 23% versus 34% of operative days, P < 0.001) and less
      lengthy OR underutilization (mean 120 versus 193 min per day of underutilization,
      P < 0.001). CONCLUSIONS: This computerized simulation demonstrates that using the
      PMS for scheduling in a single operating room increases throughput and other
      measures of surgical efficiency.

PMID- 27020813
TI  - Epigallocatechin gallate attenuates cardiopulmonary bypass-associated lung
      injury.
AB  - BACKGROUND: Lung dysfunction constitutes a severe complication after major
      cardiac surgery with cardiopulmonary bypass (CPB), substantially contributing to
      postoperative morbidity and mortality. The current possibilities of preventive
      and therapeutic interventions, however, remain insufficient. We, therefore,
      investigated the effects of intraoperative application of the antioxidant and
      anti-inflammatory green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on
      CPB-associated lung injury. MATERIALS AND METHODS: Thirty piglets (8-15 kg) were
      divided into four groups: sham-operated and saline-treated control group (n = 7);
      sham-operated and EGCG-treated control group (EGCG-control group; n = 7); CPB
      group (n = 10); and CPB + EGCG group (n = 6). The CPB groups underwent 120 min of
      CPB followed by 90 min of recovery time. In the CPB + EGCG group, EGCG (10 mg/kg
      body weight) was administered intravenously before and after CPB. Hemodynamic
      monitoring, blood gas analysis, hematoxylin-eosin staining, and
      immunohistochemistry of lung tissue were performed. RESULTS: Histologic
      examination revealed thickening of the alveolar wall and enhanced alveolar
      neutrophil infiltration in the CPB group (P < 0.05) compared with those in the
      control group, which was prevented by EGCG (P < 0.05). In the CPB group, higher
      formation of poly(ADP-ribose) and nuclear translocation of apoptosis-inducing
      factor was detected in comparison with those in the control group (P < 0.001),
      which were both reduced in the CPB + EGCG group (P < 0.001). Compared with the
      control group, the EGCG-control group showed thickening of the alveolar wall and
      increased neutrophil infiltration (P < 0.05). CONCLUSIONS: CPB leads to lung
      edema, pulmonary neutrophil infiltration, and presumably initiation of poly(ADP
      ribose) polymerase-dependent cell death signaling in the lung. EGCG appears to
      attenuate CPB-associated lung injury, suggesting that this may provide a novel
      pharmacologic approach.

PMID- 27020814
TI  - Erratum. MicroRNA expression profile of surgical removed mandibular bone tissues
      from patients with mandibular prognathism.

PMID- 27020815
TI  - Effects of intraosseous epinephrine in a cardiac arrest swine model.
AB  - BACKGROUND: Interruptions in cardiopulmonary resuscitation (CPR) to obtain
      vascular access reduces blood flow to vital organs. Tibial intraosseous (TIO)
      access may be a faster alternative to intravenous (IV) access for delivery of
      vasoactive medications. The purpose of this study was to examine the differences
      in pharmacokinetics and pharmacodynamics of TIO- and IV-delivered epinephrine.
      MATERIALS AND METHODS: A prospective, between subjects, experimental design
      comparing Cmax, Tmax, return of spontaneous circulation (ROSC), and time to ROSC.
      Adult male swine were divided into three equal groups (n = 7) all received CPR
      and defibrillation: the second group received IV epinephrine and the third group
      received tibial intraosseous epinephrine. Swine were placed in cardiac arrest for
      2 min before CPR was initiated. After 2 min of CPR, epinephrine was delivered by
      IV or TIO, and serial blood samples were collected over 4 min. RESULTS: There
      were no significant differences between IV versus TIO epinephrine in achieving
      ROSC, time to ROSC, and Cmax. A one-way analysis of variance demonstrated a
      significant difference between the IV and TIO groups in Tmax (P = 0.025). A
      Fisher exact test demonstrated a significant difference between IV epinephrine
      versus CPR/Defib only (P = 0.035) and TIO epinephrine versus CPR/Defib only (P =
      0.010) in achieving ROSC. A multivariate analysis of variance showed significant
      differences in IV versus intraosseous epinephrine concentration at specific time
      intervals: 60 (P = 0.023), 90 (P = 0.001), and 120 (P < 0.000) sec. CONCLUSIONS:
      In the context of ROSC, epinephrine delivered via TIO route is a clinically
      relevant alternative to IV administration. When IV access cannot be immediately
      obtained in cardiac arrest patients, TIO access should be considered.

PMID- 27020816
TI  - Heart rate in pediatric trauma: rethink your strategy.
AB  - BACKGROUND: The optimal heart rate (HR) for children after trauma is based on
      values derived at rest for a given age. As the stages of shock are based in part
      on HR, a better understanding of how HR varies after trauma is necessary.
      Admission HRs of pediatric trauma patients were analyzed to determine which
      ranges were associated with lowest mortality. MATERIALS AND METHODS: The National
      Trauma Data Bank was used to evaluate all injured patients ages 1-14 years
      admitted between 2007 and 2011. Patients were stratified into eight groups based
      on age. Clinical characteristics and outcomes were recorded, and regression
      analysis was used to determine mortality odds ratios (ORs) for HR ranges within
      each age group. RESULTS: A total of 214,254 pediatric trauma patients met
      inclusion criteria. The average admission HR and systolic blood pressure were
      104.7 and 120.4, respectively. Overall mortality was 0.8%. The HR range
      associated with lowest mortality varied across age groups and, in children ages 7
      14, was narrower than accepted resting HR ranges. The lowest risk of mortality
      for patients ages 5-14 was captured at HR 80-99. CONCLUSIONS: The HR associated
      with lowest mortality after pediatric trauma frequently differs from resting HR.
      Our data suggest that a 7y old with an HR of 115 bpm may be in stage III shock,
      whereas traditional HR ranges suggest that this is a normal rate for this child.
      Knowing when HR is critically high or low in the pediatric trauma population will
      better guide treatment.

PMID- 27020817
TI  - Danhong huayu koufuye prevents deep vein thrombosis through anti-inflammation in
      rats.
AB  - BACKGROUND: Danhong huayu koufuye (DHK) has traditionally been used clinically
      for a long time in China. This study was to evaluate the effect of DHK in
      treating deep vein thrombosis (DVT) in rats and explore its possible mechanism.
      METHODS: Forty-eight Sprague-Dawley rats were divided into four groups, performed
      with incomplete inferior vena cava ligation to induce DVT, and orally
      administered with DHK (3.20 mg/kg/d), warfarin (2.00 mg/kg/d), or vehicle for 7
      days. The involved inferior vena cava and thrombi were collected and measured in
      size. The tissue specimens were performed for routine histopathologic evaluation
      and immunohistochemical staining with tissue factor and matrix metalloproteinases
      9. Blood samples were collected for detecting coagulation function, blood cell
      count, and the levels of interleukin-6 and tumor necrosis factor-alpha. RESULTS:
      The treatment of DHK markedly reduced the size of thrombi by 49.26%, and the vein
      wall thickness by 47.86%. The recanalization rate was significant higher in the
      DHK-treated group than the vehicle-treated group (26.34 +/- 6.53% versus 15.91 +/
      3.93%, P < 0.01). Comparing to vehicle control, DHK significantly reduced
      neutrophils (P < 0.05) and lymphocytes (P < 0.05), serum tumor necrosis factor
      alpha level (4.90 +/- 1.14 pg/mL versus 6.60 +/- 1.62 pg/mL, P < 0.01), and the
      expression of matrix metalloproteinases-9 and tissue factor (P < 0.05) in
      thrombi. CONCLUSIONS: DHK effectively prevented DVT through anti-inflammatory
      action in rats.

PMID- 27020818
TI  - Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra
      abdominal adhesion in an experimental rat model.
AB  - BACKGROUND: Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory
      agent. We investigated the protective effect of PF against postoperative intra
      abdominal adhesions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were
      divided into three groups (n = 10 in each group). In group 1 (control), adhesion
      induction was performed by cecal abrasion, and no treatment was administered. In
      group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose
      was administered by gavage. In group 3 (PF treatment), for 2 wk after adhesion
      induction, 500-mg/kg/d PF was administered by gavage. On the 15th postoperative
      day, the animals were killed, and cecal and peritoneal tissues were excised. The
      adhesions were graded macroscopically. The protein concentrations and mRNA
      expression levels of the following genes were measured in the tissues: matrix
      metallopeptidase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1);
      tumor necrosis factor-alpha (TNF-alpha); and transforming growth factor-beta 1
      (TGF-beta1). The tissue samples were also evaluated histopathologically. RESULTS:
      Macroscopic and histopathologic evaluation showed that PF-reduced adhesion and
      inflammation (P < 0.001, P = 0.004, respectively). Pretreatment with PF-reduced
      TIMP-1, TNF-alpha, and TGF-beta1 protein concentrations (P < 0.001, P < 0.001,
      and P < 0.001, respectively) and mRNA expression levels (P = 0.030, P = 0.005,
      and P = 0.016, respectively) and increased MMP-9 protein concentrations (P <
      0.001) and mRNA expression (P = 0.021). CONCLUSIONS: The findings of this study
      suggest that PF can be used as a protective agent to prevent the development of
      peritoneal adhesions and inflammation during the postoperative period.

PMID- 27020819
TI  - Relationship between mammalian target of rapamycin and autophagy in
      lipopolysaccharide-induced lung injury.
AB  - BACKGROUND: To investigate the relationship between the mammalian target of
      rapamycin (mTOR) signaling pathway and autophagy in lung tissue cells in
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MATERIALS AND
      METHODS: Thirty-two male C57BL/6 mice were randomly assigned to four different
      treatment groups: control (C), LPS (L), rapamycin (R), and LPS + rapamycin (LR).
      Optical and electron microscopy were used to detect lung injury and autophagy.
      Tumor necrosis factor alpha, interleukin 6, and p62 in lung tissues and IgM
      concentrations and total protein in bronchoalveolar lavage fluid were evaluated
      using enzyme-linked immunosorbent assay. LC3II, LC3I, ribosomal protein p70S6
      kinase1 (p70S6K1), and phosphorylation of ribosomal protein p70S6 kinase1(P
      p70S6K1) in lung tissues were measured by Western blot. RESULTS: The L group had
      an increased ALI index (P < 0.05) compared with the C group, but there were no
      differences between the L and the LR groups or the C and R groups (all P > 0.05).
      According to the index of autophagy, the L, the R and C groups, the level of
      autophagy were in descending order (P < 0.05), there were no differences between
      the L and the LR groups (P > 0.05). The expression of P-p70S6K1 declined after
      rapamycin treatment, showing that the signaling pathway of mTOR is inhibited by
      rapamycin. CONCLUSIONS: LPS could trigger the mTOR signaling pathway and
      autophagy of lung tissue cells in LPS-induced ALI in mice; The mTOR signaling
      pathway did not play a major role in lung injury and autophagy of lung tissue
      cells induced by LPS.

PMID- 27020820
TI  - Esophageal reconstruction: posterior mediastinal or retrosternal route.
AB  - BACKGROUND: Although posterior mediastinal (PM) route and retrosternal (RS) route
      have been used for reconstruction after minimally invasive esophagectomy (MIE),
      the optimal route remains controversial. This study reviewed our experiences with
      McKeown MIEs for esophageal cancer and aimed to investigate which route was
      better for esophageal reconstruction. MATERIALS AND METHODS: From December 2011
      to December 2013, 103 patients who underwent McKeown MIE and esophageal
      reconstruction by PM or RS routes were reviewed. The decision regarding which
      approach was appropriated mainly depended on the first surgeon's preference and
      experience. Baseline demographics, operative, and postoperative data of the
      patients were analyzed. RESULTS: Fifty-six and forty-seven patients receiving PM
      and RS route reconstruction were reviewed, respectively. Shorter operation time
      (P = 0.001), less blood loss (P = 0.029), and longer route length (P < 0.001)
      were observed in PM route compared with RS route. No difference was observed in
      the resection type, harvested lymph node, intensive care unit and hospital stay,
      postoperative complications, and in-hospital mortality between the two routes
      (all P > 0.05). CONCLUSIONS: Both RS route and PM route were safe and effective.
      PM route was associated with shorter operation time, less blood loss, but longer
      route length compared with RS route.

PMID- 27020821
TI  - Ninety-day readmission after colorectal cancer surgery in a Veterans Affairs
      cohort.
AB  - BACKGROUND: Readmissions following colorectal surgery are common. However, there
      are limited data examining unplanned readmissions (URs) after colorectal cancer
      (CRC) surgery. The goal of this study was to identify reasons and predictors of
      UR, and to examine their clinical impact on CRC patients. METHODS: A
      retrospective cohort study using a prospective CRC surgery database of patients
      treated at a VA tertiary referral center was performed (2005-2011). Ninety-day
      URs were recorded and classified based on reason for readmission. Clinical impact
      of UR was measured using a validated classification for postoperative
      complications. Multivariate logistic regression analyses were performed to
      identify predictors of UR. RESULTS: 487 patients were included; 104 (21%)
      required UR. Although the majority of UR were due to surgical reasons (n = 72,
      69%), medical complications contributed to 25% of all readmission events. Nearly
      half of UR (n = 44, 40%) had significant clinical implications requiring invasive
      interventions, intensive care unit stays, or led to death. After multivariate
      logistic regression, the following independent predictors of UR were identified:
      African-American race (odds ratio [OR] 0.47 [0.27-0.88]), ostomy creation (OR
      2.50 [1.33-4.70]), and any postoperative complication (OR 4.36 [2.48-7.68]).
      CONCLUSIONS: Ninety-day URs following colorectal cancer surgery are common, and
      represent serious events associated with worse outcomes. In addition to
      postoperative complications, surgical details that can be anticipated (i.e.,
      ileostomy creation) and medical events unrelated to surgery, both contribute as
      important and potentially preventable reasons for UR. Future studies should focus
      on developing and examining interventions focused at improving the process of
      perioperative care for this high-risk population.

PMID- 27020822
TI  - Efficacy of gelatin gel sheets in sustaining the release of basic fibroblast
      growth factor for murine skin defects.
AB  - BACKGROUND: Gelatin has been used as a material sustaining the release of basic
      fibroblast growth factor (bFGF), which promotes fibroblast proliferation and
      capillary formation and accelerates wound healing. In the application of these
      materials, bFGF is impregnated immediately before application, and it is
      difficult to conform the shape to the wound. In this study, we prepared a pliable
      and plastic gelatin gel sheet (GGS) that sustains bFGF and conforms to the shape
      of the wound as a result of cross-linking just before application. In addition,
      we examined the sustained release profile of bFGF from GGS and its effect on
      wound healing in murine skin defects. MATERIALS AND METHODS: A 13-wt% gelatin
      solution was mixed with bFGF before cross-linking with 1% glutaraldehyde
      solution. GGSs impregnated with 7 MUg/cm(2) of bFGF were incubated in phosphate
      buffered saline and collagenase solution, and GGS degradation and bFGF release
      were evaluated. In the murine experiments, GGSs treated without bFGF and GGSs
      impregnated with 1, 3.5, 7, or 14 MUg/cm(2) of bFGF were applied to full
      thickness skin defects created on the backs of C57BL/6JJcl mice, and the wound
      closure, epithelial length, extent of granulation tissue and capillary formation
      were compared. RESULTS: bFGF was released according to the degradation of GGS in
      phosphate-buffered saline, and the remaining bFGF was released in collagenase
      solution. In the animal studies, epithelialization was accelerated in the GGSs
      treated with 1 and 3.5 MUg/cm(2) of bFGF, and granulation tissue formation and
      angiogenesis were promoted based on the amount of bFGF impregnated into the GGS.
      CONCLUSIONS: GGS impregnated with bFGF is capable of sustaining the release of
      bFGF, with consequent accelerated epithelialization, granulation tissue
      formation, and angiogenesis in vivo. GGS is a novel and promising wound dressing
      that sustains bFGF and can be adapted to the shape of various wounds in the
      treatment of both acute and chronic wounds.

PMID- 27020823
TI  - A bitter pill to swallow: dysphagia in cervical spine injury.
AB  - BACKGROUND: Dysphagia is a common complication after cervical spine trauma with
      spinal cord injury. We sought to characterize the prevalence of dysphagia within
      a total cervical spinal injury (CSI) population, considering the implications of
      spinal cord injury status and age on dysphagia development. We hypothesized that
      while greater rates of dysphagia would be found in geriatric and spinal cord
      injured subgroups, all patients presenting with CSI would be at heightened risk
      for swallowing dysfunction. METHODS: All trauma admissions to a level II trauma
      center from January 2010 to April 2014 with CSI were retrospectively reviewed.
      CSI was classified as any ligamentous or cervical spinous fracture with or
      without cord injury. Patients failing a formal swallow evaluation were considered
      dysphagic. The implications of dysphagia development on age and spinal cord
      injury status were assessed in univariate and multivariate analyses. RESULTS: A
      total of 481 patients met study inclusion criteria, of which 123 (26%) developed
      dysphagia. Within the dysphagic subpopulation, 90 patients (73%) were geriatric,
      and 23 (19%) sustained spinal cord injury. The dysphagic subpopulation was
      predominantly free from spinal cord injury (81%). Multivariate analyses found age
      (adjusted odds ratio: 1.06; 95% confidence interval 1.04-1.07; P < 0.001) and
      spinal cord injury (adjusted odds ratio: 2.69; 95% confidence interval 1.30-5.56;
      P = 0.008) to be significant predictors of dysphagia development. CONCLUSIONS:
      Despite spinal cord-injured patients being at increased risk for dysphagia, most
      of the dysphagic subpopulation was free from spinal cord injury. Geriatric and
      CSI patients with or without cord injury should be at heightened suspicion for
      dysphagia development.

PMID- 27020824
TI  - Trauma indices for prediction of acute respiratory distress syndrome.
AB  - BACKGROUND: A myriad of trauma indices has been validated to predict probability
      of trauma survival. We aimed to compare the performance of commonly used indices
      for the development of the acute respiratory distress syndrome (ARDS). MATERIALS
      AND METHODS: Historic, observational cohort study of 27,385 consecutive patients
      admitted to a statewide referral trauma center between July 11, 2003 and October
      31, 2011. A validated algorithm was adapted to identify patients with ARDS. Each
      trauma index was evaluated in logistic regression using the area under the
      receiver operating characteristic curve. RESULTS: The case rate for ARDS
      development was 5.8% (1594). The receiver operating characteristics for injury
      severity score (ISS) had the best discrimination and had an area under the curve
      of 0.88 (95% confidence interval [CI] = 0.87-0.89). Glasgow coma score (0.71, 95%
      CI = 0.70-0.73), A Severity Characterization of Trauma (0.86, 95% CI = 0.85
      0.87), Revised Trauma Score (0.71, 95% CI = 0.70-0.72) and thorax Abbreviated
      Injury Score (0.73, 95% CI = 0.72-0.74) performed worse (P < 0.001) and Trauma
      and Injury Severity Score (0.88, 95% CI = 0.87-0.88) performed equivocally (P =
      0.51) in comparison to ISS. Using a cutoff point ISS >=16, sensitivity and
      specificity were 84.9% (95% CI = 83.0%-86.6%) and 75.6% (95% CI = 75.1%-76.2%),
      respectively. CONCLUSIONS: Among commonly used trauma indices, ISS has superior
      or equivocal discriminative ability for development of ARDS. A cutoff point of
      ISS >=16 provided good sensitivity and specificity. The use of ISS >=16 is a
      simple method to evaluate ARDS in trauma epidemiology and outcomes research.

PMID- 27020825
TI  - Best practices to optimize intraoperative photography.
AB  - BACKGROUND: Intraoperative photography is used extensively for communication,
      research, or teaching. The objective of the present work was to define, using a
      standardized methodology and literature review, the best technical conditions for
      intraoperative photography. MATERIALS AND METHODS: Using either a smartphone
      camera, a bridge camera, or a single-lens reflex (SLR) camera, photographs were
      taken under various standard conditions by a professional photographer. All
      images were independently assessed blinded to technical conditions to define the
      best shooting conditions and methods. RESULTS: For better photographs, an SLR
      camera with manual settings should be used. Photographs should be centered and
      taken vertically and orthogonal to the surgical field with a linear scale to
      avoid error in perspective. The shooting distance should be about 75 cm using an
      80-100-mm focal lens. Flash should be avoided and scialytic low-powered light
      should be used without focus. The operative field should be clean, wet surfaces
      should be avoided, and metal instruments should be hidden to avoid reflections.
      For SLR camera, International Organization for Standardization speed should be as
      low as possible, autofocus area selection mode should be on single point AF,
      shutter speed should be above 1/100 second, and aperture should be as narrow as
      possible, above f/8. For smartphone, use high dynamic range setting if available,
      use of flash, digital filter, effect apps, and digital zoom is not recommended.
      CONCLUSIONS: If a few basic technical rules are known and applied, high-quality
      photographs can be taken by amateur photographers and fit the standards accepted
      in clinical practice, academic communication, and publications.

PMID- 27020826
TI  - High-fat enteral nutrition controls intestinal inflammation and improves
      intestinal motility after peritoneal air exposure.
AB  - BACKGROUND: Peritoneal air exposure is a common phenomenon in abdominal surgery,
      but long-term exposure could induce intestinal inflammatory responses, resulting
      in delayed recovery of gastrointestinal motility after surgery. High-fat enteral
      nutrition has been reported to ameliorate inflammation in many diseases. In the
      present study, we investigated whether high-fat enteral nutrition could control
      intestinal inflammation and improve intestinal motility after peritoneal air
      exposure. METHODS: Male adult rats were administrated saline, low-fat enteral
      nutrition, or high-fat enteral nutrition via gavage before and after peritoneal
      air exposure for 3 h. Control rats underwent anesthesia without laparotomy and
      received saline. Intestinal motility was assessed 24 h after surgery by charcoal
      transport assay; systemic inflammation was assessed by analyzing serum levels of
      tumor necrosis factor alpha, interleukin (IL)-1beta, IL-6, and IL-10; and
      intestinal inflammation was assessed by analyzing myeloperoxidase activity and
      concentrations and gene expression of tumor necrosis factor alpha, IL-1beta, IL
      6, and IL-10 in the intestinal tissue. RESULTS: Peritoneal air exposure decreased
      intestinal motility significantly compared with the control group (P < 0.05). The
      systemic and intestinal inflammatory parameters were also much higher in the
      peritoneal air exposure groups than in the control group. Both low-fat and high
      fat enteral nutrition increased intestinal motility and reduced systemic and
      intestinal inflammatory parameter levels to different degrees. However, high-fat
      enteral nutrition significantly improved the negative alterations in these
      biochemical parameters compared with low-fat enteral nutrition (P < 0.05).
      CONCLUSIONS: These results suggest that high-fat enteral nutrition might be able
      to control intestinal inflammation and improve intestinal motility after
      peritoneal air exposure. Thus, the perioperative administration of high-fat
      enteral nutrition may be a promising treatment to enhance the recovery of
      intestinal motility after surgery.

PMID- 27020827
TI  - Bovine fetal collagen reinforcement in a small animal model of hernia with
      component repair.
AB  - BACKGROUND: Component separation is a surgical strategy used to achieve abdominal
      wall reconstruction for patients with significant ventral hernias. With an
      increasing number of variations in procedural techniques and materials, the
      development of a small animal model of this surgery would allow for the
      controlled evaluation of variables with analytics not available in human clinical
      studies. To test this model, we investigated the reinforcement of these component
      repairs in rats with a bovine fetal collagen (BFC) scaffold. METHODS: Fifty
      Sprague Dawley rats were randomized into either component repair alone or BFC
      reinforced component repair. At time points up to 1 y, these groups were
      evaluated for hernia formation, strength of repair, strength of mesh-muscle
      interface, and histology of the repair site. RESULTS: Anterior component
      separation was achievable and reproducible in this small animal model.
      Significantly fewer hernias were found in BFC reinforced repairs. The change in
      transverse abdominal length was lower for reinforced repairs indicating less
      external oblique retraction, and reinforced repairs were consistently stronger
      than controls through 1 y. BFC was revascularized and repopulated with host cells
      but not rapidly degraded. CONCLUSIONS: This small animal model of hernia repair
      with anterior component separation was effective in evaluating the reinforcement
      of a hernia repair with mesh. It may be useful in future work for the controlled,
      comparative investigation of different repair techniques and mesh materials in
      anterior component separation hernia repairs. Additionally, bovine fetal collagen
      was found to effectively reinforce component repairs and undergo an assimilation
      process including rapid revascularization and repopulation with host cells
      followed by gradual extracellular matrix remodeling.

PMID- 27020828
TI  - Oxygen saturation monitoring using resonance Raman spectroscopy.
AB  - BACKGROUND: The knowledge of hemoglobin oxygen saturation (SO2) and tissue
      oxygenation is critical to identify the presence of shock and therapeutic
      options. The resonance vibrational enhancement of hemoglobin allows measurement
      of oxy- and deoxy species of hemoglobin and resonance Raman spectroscopy (RRS
      StO2) has been successfully used to measure aggregate microvascular oxygenation.
      We tested the hypothesis that noninvasive oxygen saturation measured by RRS-StO2
      could serve as surrogate of systemic central venous SO2. METHODS: In anesthetized
      rats, measurements of RRS-StO2 made in oral mucosa, skin, muscle, and liver were
      compared with measurements of central venous SO2 using traditional multi
      wavelength oximetry. Various oxygenation levels were obtained using a stepwise
      hemorrhage while over 100 paired blood samples and Raman-based measurements were
      performed. The relationships between RRS-StO2 and clinically important systemic
      blood parameters were also evaluated. RRS-StO2 measurements were made in 3-mm
      diameter tissue areas using a microvascular oximeter and a handheld probe.
      RESULTS: Significant correlations were found between venous SO2 and RRS-StO2
      measurements made in the oral mucosa (r = 0.913, P < 0.001), skin (r = 0.499, P <
      0.01), and liver (r = 0.611, P < 0.05). The mean difference between sublingual
      RRS-StO2 and blood sample SO2 values was 5.4 +/- 1.6%. Sublingual RRS-StO2 also
      correlated with lactate (r = 0.909, P < 0.01), potassium (r = 0.757, P < 0.01),
      and pH (r = 0.703, P < 0.05). CONCLUSIONS: Raman-based oxygen saturation is a
      promising technique for the noninvasive evaluation of oxygenation in skin, thin
      tissues, and solid organs. Under certain conditions, sublingual RRS-StO2
      measurements correlate with central venous SO2.

PMID- 27020829
TI  - Pediatric surgeon-directed wound classification improves accuracy.
AB  - BACKGROUND: Surgical wound classification (SWC) communicates the degree of
      contamination in the surgical field and is used to stratify risk of surgical site
      infection and compare outcomes among centers. We hypothesized that by changing
      from nurse-directed to surgeon-directed SWC during a structured operative
      debrief, we will improve accuracy of documentation. METHODS: An institutional
      review board-approved retrospective chart review was performed. Two time periods
      were defined: initially, SWC was determined and recorded by the circulating nurse
      (before debrief, June 2012-May 2013) and allowing 6 mo for adoption and
      education, we implemented a structured operative debriefing including surgeon
      directed SWC (after debrief, January 2014-August 2014). Accuracy of SWC was
      determined for four commonly performed pediatric general surgery operations:
      inguinal hernia repair (clean), gastrostomy +/- Nissen fundoplication (clean
      contaminated), appendectomy without perforation (contaminated), and appendectomy
      with perforation (dirty). RESULTS: One hundred eighty-three cases before debrief
      and 142 cases after debrief met inclusion criteria. No differences between time
      periods were noted in regard to patient demographics, ASA class, or case mix.
      Accuracy of wound classification improved before debrief (42% versus 58.5%, P =
      0.003). Before debrief, 26.8% of cases were overestimated or underestimated by
      more than one wound class, versus 3.5% of cases after debrief (P < 0.001).
      Interestingly, most after debrief contaminated cases were incorrectly classified
      as clean contaminated. CONCLUSIONS: Implementation of a structured operative
      debrief including surgeon-directed SWC improves the percentage of correctly
      classified wounds and decreases the degree of inaccuracy in incorrectly
      classified cases. However, after implementation of the debriefing, we still
      observed a 41.5% rate of incorrect documentation, most notably in contaminated
      cases, indicating further education and process improvement is needed.

PMID- 27020830
TI  - Repetitive shock wave therapy improves muscular microcirculation.
AB  - BACKGROUND: Extracorporeal shock wave therapy (ESWT) is mainly applied in tendon
      as well as bone problems based on stem-cell activation and healing acceleration.
      The effect of ESWT on muscle tissue is much less understood to date. However,
      from a clinical perspective, muscle injuries are of distinct interest especially
      in elite athletes such as soccer players. MATERIAL AND METHODS: A total of 26
      rats were randomized into two groups. Group A received a single application of
      high-energetic focused ESWT (0.3 mJ/mm(2), 4 Hz, 1000 impulses, 10 J), whereas
      group B underwent the same procedure every 10 min for three sessions (3 * 0.3
      mJ/mm(2), 4 Hz, 3 * 1000 impulses, totaling 30 J). Blood flow at a depth of 8 mm
      was measured continuously and noninvasively by a combined Laser-Doppler-Imaging
      and photospectrometric technique (Oxygen-to-see, O2C, LEA Medizintechnik,
      Germany). RESULTS: One minute after the application of high-energy ESWT blood
      flow in group A increased by 16.5% (P = 0.007). Thereafter, it decreased from
      minute 2 after application and remained significantly unchanged to baseline value
      until the end of the measuring period at 50 min (P = 0.550). Group B showed a
      similar significant increase in blood flow of 16.4% (P = 0.049) and a decrease
      afterward, too. After the second focused ESWT blood flow was boosted to 26.6% (P
      = 0.004), remaining significantly elevated until the third application was
      initiated. Muscular blood flow was increased to 29.8% after the third focused
      ESWT (P < 0.001), remaining significantly increased for another 10 min.
      CONCLUSIONS: Focused ESWT enhances blood flow in the muscle of rats. Moreover,
      repetitive ESWT extended this beneficial effect.

PMID- 27020831
TI  - Efficacy of gelatin gel sheets sustaining epidermal growth factor for murine skin
      defects.
AB  - BACKGROUND: Epidermal growth factor (EGF) plays an important role in wound
      healing. However, EGF must be applied daily due to rapid inactivation in vivo. We
      investigated the sustained release of EGF from gelatin gel sheets (GGSs) and the
      efficacy of GGSs impregnated with EGF for promoting wound healing. MATERIALS AND
      METHODS: GGSs impregnated with EGF were prepared by cross-linking via
      glutaraldehyde to gelatin solution containing EGF. The sustained release of EGF
      and the bioactivity of released EGF were evaluated. Then, three kinds of GGSs
      containing NSS (normal saline solution; NSS group), 2.5 MUg of EGF (EGF-L group),
      or 25 MUg of EGF (EGF-H group) were applied to full-thickness skin defects
      created on the backs of mice. The wounds covered with polyurethane film without
      GGS were used as a control (PUF group). The wound area, neoepithelium length,
      regenerated granulation tissue, and newly formed capillaries were evaluated.
      RESULTS: EGF was sustained and released from GGS as it degraded. The bioactivity
      of released EGF was confirmed. EGF-L group promoted the neoepithelium length,
      regenerated granulation tissue, and newly formed capillaries compared with those
      in the PUF and NSS groups. The area of regenerated granulation tissue in the NSS
      group (week 1: 2.6 + 0.2 mm(2), week 2: 2.8 + 0.3 mm(2)) was larger than that in
      the PUF group (week 1: 0.6 + 0.1 mm(2), week 2: 1.0 + 0.1 mm(2)). The area of
      newly formed capillaries in the EGF-L group (9967 + 1903 MUm(2)) was larger than
      that of the EGF-H group (3485 + 1050 MUm(2)). CONCLUSIONS: GGSs impregnated with
      EGF-L showed promising results regarding wound healing.

PMID- 27020832
TI  - Pediatric burns: Kids' Inpatient Database vs the National Burn Repository.
AB  - OBJECTIVE: Burn injuries are one of the leading causes of morbidity and mortality
      in young children. The Kids' Inpatient Database (KID) and National Burn
      Repository (NBR) are two large national databases that can be used to evaluate
      outcomes and help quality improvement in burn care. Differences in the design of
      the KID and NBR could lead to differing results affecting resultant conclusions
      and quality improvement programs. This study was designed to validate the use of
      KID for burn epidemiologic studies, as an adjunct to the NBR. METHODS: Using the
      KID (2003, 2006, and 2009), a total of 17,300 nonelective burn patients younger
      than 20 y old were identified. Data from 13,828 similar patients were collected
      from the NBR. Outcome variables were compared between the two databases. RESULTS:
      Comparisons revealed similar patient distribution by gender, race, and burn size.
      Inhalation injury was more common among the NBR patients and was associated with
      increased mortality. The rates of respiratory failure, wound infection,
      cellulitis, sepsis, and urinary tract infection were higher in the KID. Multiple
      regression analysis adjusting for potential confounders demonstrated similar
      mortality rate but significantly longer length of stay for patients in the NBR.
      CONCLUSIONS: Despite differences in the design and sampling of the KID and NBR,
      the overall demographic and mortality results are similar. The differences in
      complication rate and length of stay should be explored by further studies to
      clarify underlying causes. Investigations into these differences should also
      better inform strategies to improve burn prevention and treatment.

PMID- 27020833
TI  - The effect of natural extracts on laser burn wound healing.
AB  - BACKGROUND: Despite the achievements in modern medicine, there is no effective
      natural treatment of second-degree burns till now. Therefore, the purpose of this
      study was to assess the wound-healing efficiency of three extracted oils, from
      the prickly pear, pumpkin and linseed on partial-thickness burns induced by
      fractional CO2 laser (an innovative up-to-date technique) in rats. MATERIALS AND
      METHODS: Thirty rats completing partial-thickness burns by fractional CO2 laser
      were randomly divided into five groups. The burns were measured, photographed,
      and topically treated daily with saline solution, "CYTOL BASIC," pumpkin-,
      linseed-, and prickly pear-extracted oils (0.52 MUL/mm(2) of oil) until day 7.
      The response to treatments was assessed by macroscopic, histologic, and
      biochemical parameters. RESULTS: Due to their chemical composition, the extracted
      oils showed significant improvements over the control and reference groups during
      the trial for both general wound appearance and crusting. On day 7, the prickly
      pear, linseed, and pumpkin oils showed a significant decrease in the healing time
      (0 cm(2), 0.15 cm(2), and 0.18 cm(2), respectively) when compared to the control
      and reference groups (1.49 cm(2) and 0.85 cm(2)). Histologic assessment of the
      prickly pear oil-treated group revealed good healing proprieties compared with
      the other groups. The collagen content in prickly pear oil-treated group was
      found to be significantly greater (270.67 +/- 7.48) than that in all other
      groups. CONCLUSIONS: Our experiment has shown, for the first time, a scientific
      evidence of the efficiency of extracted oils of prickly pear, pumpkin, and
      linseed on partial-thickness burns.

PMID- 27020834
TI  - One-hour PTH after thyroidectomy predicts symptomatic hypocalcemia.
AB  - BACKGROUND: A major morbidity after total thyroidectomy is hypocalcemia. Although
      many clinical factors and laboratory studies have been correlated with both
      biochemical and symptomatic hypocalcemia, the ideal use and timing of these tests
      remain unclear. We hypothesize 1-h (PACU) parathyroid hormone (PTH) will identify
      patients at risk for symptomatic hypocalcemia. METHODS: This prospective study
      evaluated 196 patients undergoing total thyroidectomy. Serum calcium and PTH
      levels were measured 1 h after surgery and on postoperative day 1 (POD1).
      Performance of a central compartment lymph node dissection, parathyroid
      autotransplantation, indication for procedure, pathology, and presence of
      parathyroid tissue in the pathology specimen were recorded. RESULTS: Of 196
      patients, nine (4.6%) developed symptomatic hypocalcemia. Thirty four (17.3%) had
      a 1-h PACU PTH <=10 pg/dL, whereas 31 (15.8%) had a POD1 PTH of <=10. Five (56%)
      of the nine symptomatic patients underwent central compartment lymph node
      dissection, four (44%) had parathyroid autotransplantation, and four (44%) had a
      PACU PTH <=10. PACU and POD1 PTH levels were correlated (R(2) = 0.682).
      Multivariate regression identified central compartment dissection,
      autotransplantation, and PACU or POD1 PTH correlated with symptomatic
      hypocalcemia. PACU PTH, POD1 PTH, PACU Ca, malignant final pathology, and age
      <=45 y correlated with biochemical hypocalcemia. CONCLUSIONS: A 1-h postoperative
      PACU PTH is equivalent to POD1 PTH in predicting the development of symptomatic
      hypocalcemia. Biochemical hypocalcemia was not predictive of symptoms in the
      immediate postoperative period. Lymph node dissection and parathyroid
      autotransplantation correlated with symptomatic hypocalcemia and improve the
      sensitivity of biochemical screening alone.

PMID- 27020835
TI  - Blocking NAD(+)/CD38/cADPR/Ca(2+) pathway in sepsis prevents organ damage.
AB  - BACKGROUND: Although the nicotinamide adenine dinucleotide (NAD(+))/CD38/cyclic
      ADP ribose (cADPR)/Ca(2+) signaling pathway has been shown to regulate
      intracellular calcium homeostasis and functions in multiple inflammatory
      processes, its role in sepsis remains unknown. The aim of this study was to
      determine whether the NAD(+)/CD38/cADPR/Ca(2+) signaling pathway is activated
      during sepsis and whether an inhibitor of this pathway, 8-Br-cADPR, protects the
      organs from sepsis-induced damage. MATERIALS AND METHODS: Male Sprague-Dawley
      rats were subjected to cecal ligation and puncture (CLP) or sham laparotomies.
      NAD(+), cADPR, CD38, and intracellular Ca(2+) levels were measured in the hearts,
      livers, and kidneys of septic rats at 0, 6, 12, 24, and 48 h after CLP surgery.
      Rats were also divided into sham, CLP, and CLP+8-Br-cADPR groups, and the hearts,
      livers, and kidneys were hematoxylin-eosin-stained and assayed for
      malondialdehyde and superoxide dismutase activities. RESULTS: NAD(+), cADPR,
      CD38, and intracellular Ca(2+) levels increased in the hearts, livers, and
      kidneys of septic rats as early as 6-24 h after CLP surgery. Treatment with 8-Br
      cADPR inhibited sepsis-induced intracellular Ca(2+) mobilization, attenuated
      tissue injury, reduced malondialdehyde levels, and increased superoxide dismutase
      activity in septic rats. CONCLUSIONS: The NAD(+)/CD38/cADPR/Ca(2+) signaling
      pathway was activated during sepsis in the CLP rat model. Blocking this pathway
      with 8-Br-cADPR protected hearts, livers, and kidneys from sepsis-induced damage.

PMID- 27020836
TI  - Chitosan hydrogels significantly limit left ventricular infarction and remodeling
      and preserve myocardial contractility.
AB  - BACKGROUND: Left ventricular myocardial infarctions (MIs) consist of a central
      area of myocardial necrosis that is surrounded by areas of myocardial injury and
      ischemia. We hypothesized that chitosan hydrogels, when injected around the
      perimeter of MIs in rats, could decrease left ventricle (LV) wall stress by the
      Law of LaPlace, and therefore myocardial oxygen requirements, and prevent the
      ischemic and injured myocardium from becoming necrotic. In this manner, chitosan
      gels could limit LV infraction size and LV remodeling. Chitosan hydrogels are
      liquid at 25 degrees C but gel at 37 degrees C. METHODS: Seventy Sprague-Dawley
      rats with ligation of the left coronary artery were treated with either
      Dulbecco's Modified Eagle Medium (DMEM) or chitosan hydrogel in DMEM, which was
      injected around the infarct perimeter. Echocardiograms were obtained before MI
      and at 2, 4, 8, 12, and 16 wk after MI. Hearts from randomly selected rats were
      harvested at baseline and at the time of echocardiography for determinations of
      LV infarct size, remodeling, and histopathology. RESULTS: Infarct sizes as a
      percentage of the total ventricular myocardium in the DMEM group averaged 17%
      versus 14% in the chitosan group at 4 wk (P < 0.05), 18% versus 14% at 8 wk (P <
      0.01), 19% versus 14% at 12 wk (P < 0.001), and 20% versus 14% at 16 wk (P <
      0.001). Injection of chitosan into the infarctions produced LV wall thicknesses
      in the MI border zones that averaged 0.66 cm at 4 wk, which were greater than the
      LV wall thicknesses in the border zones of rats treated with DMEM, which averaged
      0.33 cm (P < 0.01). Arteriole densities in the MI border zones were 160/mm(2) in
      the chitosan group but only 92/mm(2) in the DMEM rats (P < 0.01). The left
      ventricular end-diastolic diameters (LVEDs) in the rats averaged 0.73 cm before
      MI. After MI, LVED increased in the DMEM rats to 0.84 cm at 2 wk, then 0.89 cm at
      4 wk, 0.89 cm at 8 wk, 0.89 m at 12 wk, and 0.87 cm at 16 wk. In contrast, LVED
      in the chitosan rats were on average 19% smaller in comparison with the DMEM rats
      (P < 0.05) and did not significantly change in comparison with their baseline
      LVEDs. Left ventricular ejection fraction (LVEF) in the rats averaged 83% before
      infarctions. In the infarction + DMEM group, the LVEFs significantly decreased
      after MI and averaged 59.7% at 2 wk, 52.5% at 4 wk, 46.1% at 8 wk, 52.4% at 12
      wk, and 53.6% at 16 wk (P < 0.05). In the infarction + chitosan-treated rats, the
      LVEFs were greater and averaged 67.8% at 2 wk (P < 0.02), 68.9% (P < 0.02) at 4
      wk, 69% (P < 0.003) at 8 wk, 65.2% at 12 wk (P < 0.05), and 67% at 16 wk (P <
      0.05). CONCLUSIONS: Chitosan gel can increase LV myocardial wall thickness,
      decrease infarct size and LV remodeling, and preserve LV contractility.

PMID- 27020837
TI  - Fentanyl sublingual spray for breakthrough cancer pain in patients receiving
      transdermal fentanyl.
AB  - AIM: To investigate the relationship between effective fentanyl sublingual spray
      (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC)
      transdermal fentanyl patch (TFP). METHODS: Adults tolerating ATC opioids received
      open-label FSS for 26 days, followed by a 26-day double-blind phase for patients
      achieving an effective dose (100-1600 ug). RESULTS: Out of 50 patients on ATC TFP
      at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately
      correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased
      during the study. Common adverse event included nausea (9%) and peripheral edema
      (9%). CONCLUSION: FSS can be safely titrated to an effective dose for BTCP in
      patients receiving ATC TFP as chronic cancer pain medication. ClinicalTrials.gov
      identifier: NCT00538850.

PMID- 27020838
TI  - Adhesion and removal kinetics of Bacillus cereus biofilms on Ni-PTFE modified
      stainless steel.
AB  - Biofilm control remains a challenge to food safety. A well-studied non-fouling
      coating involves codeposition of polytetrafluoroethylene (PTFE) during
      electroless plating. This coating has been reported to reduce foulant build-up
      during pasteurization, but opportunities remain in demonstrating its efficacy in
      inhibiting biofilm formation. Herein, the initial adhesion, biofilm formation,
      and removal kinetics of Bacillus cereus on Ni-PTFE-modified stainless steel (SS)
      are characterized. Coatings lowered the surface energy of SS and reduced biofilm
      formation by > 2 log CFU cm(-2). Characterization of the kinetics of biofilm
      removal during cleaning demonstrated improved cleanability on the Ni-PTFE coated
      steel. There was no evidence of biofilm after cleaning by either solution on the
      Ni-PTFE coated steel, whereas more than 3 log and 1 log CFU cm(-2) of bacteria
      remained on the native steel after cleaning with water and an alkaline cleaner,
      respectively. This work demonstrates the potential application of Ni-PTFE non
      fouling coatings on SS to improve food safety by reducing biofilm formation and
      improving the cleaning efficiency of food processing equipment. 

PMID- 27020839
TI  - Surface degeneration of W crystal irradiated with low-energy hydrogen ions.
AB  - The damage layer of a W (100) crystal irradiated with 120 eV hydrogen ions at a
      fluence of up to 1.5 * 10(25)/m(2) was investigated by scanning electron
      microscopy and conductive atomic force microscopy (CAFM). The periodic surface
      degeneration of the W crystal at a surface temperature of 373 K was formed at
      increasing hydrogen fluence. Observations by CCD camera and CAFM indicate the
      existence of ultrathin surface layers due to low-energy H irradiation. The W
      surface layer can contain a high density of nanometer-sized defects, resulting in
      the thermal instability of W atoms in the surface layer. Our findings suggest
      that the periodic surface degeneration of the W crystal can be ascribed to the
      lateral erosion of W surface layers falling off during the low-energy hydrogen
      irradiation. Our density functional theory calculations confirm the thermal
      instability of W atoms in the top layer, especially if H atoms are adsorbed on
      the surface.

PMID- 27020840
TI  - The acceptability to patients of PhysioDirect telephone assessment and advice
      services; a qualitative interview study.
AB  - BACKGROUND: In response to long waiting lists and problems with access to primary
      care physiotherapy, several Primary Care Trusts (PCTs) (now Clinical
      Commissioning Groups CCGs) developed physiotherapy-led telephone assessment and
      treatment services. The Medical Research Council (MRC) funded PhysioDirect trial
      was a randomised control trial (RCT) in four PCTs, with a total of 2252 patients
      that compared this approach with usual physiotherapy care. This nested
      qualitative study aimed to explore the acceptability of the PhysioDirect
      telephone assessment and advice service to patients with musculoskeletal
      conditions. METHODS: We conducted 57 semi-structured interviews with adults from
      4 PCTs who were referred from general practice to physiotherapy with
      musculoskeletal conditions and were participating in the PhysioDirect trial. The
      Framework method was used to analyse the qualitative data. RESULTS: The
      PhysioDirect service was largely viewed as acceptable although some saw it as a
      first step to subsequent face-to-face physiotherapy. Most participants found
      accessing the PhysioDirect service straightforward and smooth, and they valued
      the faster access to physiotherapy advice offered by the telephone service.
      Participants generally viewed both the PhysioDirect service and the
      physiotherapists providing the service as helpful. Participants' preferences and
      priorities for treatment defined the acceptable features of PhysioDirect but the
      acceptable features were traded off against less acceptable features. Some
      participants felt that the PhysioDirect service was impersonal and impaired the
      development of a good relationship with their physiotherapist, which made the
      service feel remote and less valuable. CONCLUSION: The PhysioDirect service was
      broadly acceptable to participants since it provided faster access to
      physiotherapy advice for their musculoskeletal conditions. Participants felt that
      it is best placed as one method of accessing physiotherapy services, in addition
      to, rather than as a replacement for, more traditional face-to-face physiotherapy
      assessment and treatment.

PMID- 27020841
TI  - Low-Grade Myofibroblastic Sarcoma in the Mandibular Canal: A Case Report.
AB  - Low-grade myofibroblastic sarcoma (LGMS) represents an atypical myofibroblastic
      tumor characterized by a diffusely infiltrating pattern of spindle-shaped tumor
      cells. It was classified as a distinct soft tissue tumor by the World Health
      Organization in 2002. LGMS occurs mostly in adult patients and has a predilection
      for the head and neck region. So far, only a few cases of LGMS located in the
      mandible have been reported. Aggressive surgical resection with clear margins is
      the primary treatment for LGMS. Because of its rarity, reports of radiation
      therapy are limited, and the therapeutic effect is still controversial. We
      present the case of an 8-year-old girl with LGMS of the mandibular canal to
      highlight the clinical features and rarity and to improve the understanding of
      the therapeutic effect of radiotherapy on LGMS. 

PMID- 27020843
TI  - Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of Soluble
      Epoxide Hydrolase Enzyme.
AB  - Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile
      erection; therefore, sEH could be useful for management of erectile dysfunction.
      Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for
      their sEH inhibition potential. Fifteen extracts showed >50% inhibition when
      screened at 50 ug/mL in sEH inhibition assay. Methanolic extract of Moringa
      oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 +/- 0.1
      ug/mL and was selected for in vitro studies on isolated rat corpus cavernosum
      smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats.
      Rats were divided into five groups, each containing six animals and treated
      orally with either water, vehicle (1% Tween-20), MEMO (45 and 90 mg/kg/day for 21
      days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of
      female rats were used, and the effect of MEMO and sildenafil was compared with
      that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth
      muscle at 0.1-100 ug/mL in vitro and significantly increased (p < 0.05) sexual
      activity, intracavernous pressure/mean arterial pressure in normal and diabetic
      rats. The increase in erectile function of rats by MEMO could be because of its
      sEH inhibitory activity. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27020842
TI  - "Mitochondrial neuropathies": A survey from the large cohort of the Italian
      Network.
AB  - Involvement of the peripheral nervous system in mitochondrial disorders has been
      previously reported. However, the prevalence of peripheral neuropathy in
      mitochondrial disorders is still unclear. Based on the large database of the
      "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we
      reviewed the clinical data of 1200 patients, with special regard to peripheral
      neuropathy (mean age at onset 24.3 +/- 20.1 years; age at last evaluation 39.8 +/
      22.3 years; females 52.7%; childhood onset [before age 16 years] 43.1%).
      Peripheral neuropathy was present in 143/1156 patients (12.4%), being one of the
      ten most common signs and symptoms. POLG mutations cause a potentially painful,
      axonal/mixed, mainly sensory polyneuropathy; TYMP mutations lead to a
      demyelinating sensory-motor polyneuropathy; SURF1 mutations are associated with a
      demyelinating/mixed sensory-motor polyneuropathy. The only mtDNA mutation
      consistently associated with peripheral neuropathy (although less severely than
      in the above-considered nuclear genes) was the m.8993T > G (or the rarer T > C)
      changes, which lead to an axonal, mainly sensory polyneuropathy. In conclusion,
      peripheral neuropathy is one of the most common features of a mitochondrial
      disorder, and may negatively impact on the quality of life of these patients.
      Furthermore, the presence or absence of peripheral neuropathy, as well as its
      specific forms and the association with neuropathic pain (indicative of a POLG
      associated disease) can guide the molecular analysis. 

PMID- 27020844
TI  - Binding of chemical warfare agent simulants as guests in a coordination cage:
      contributions to binding and a fluorescence-based response.
AB  - Cubic coordination cages act as competent hosts for several alkyl phosphonates
      used as chemical warfare agent simulants; a range of cage/guest structures have
      been determined, contributions to guest binding analysed, and a fluorescent
      response to guest binding demonstrated. 

PMID- 27020846
TI  - The effects of the Pilates method in the elderly: a systematic review.
AB  - Several studies show the benefits of including muscle strength and aerobic
      physical activity in the routine of elderly people. Among the various
      possibilities of physical activity, the Pilates method has become a popular
      modality in recent years, through a system of exercises enabling to work the
      whole body and that corrects posture and realigns the muscles, developing the
      body stability needed for a healthier life. The aim of this study was to review
      the current evidence on the effects of the practice of the Pilates method in the
      elderly. A systematic literature review was conducted in the following electronic
      databases: Pubmed, Scielo, Lilacs/Bireme, Scopus, Pedro and Isi of Knowledge,
      from descriptors pilates, elderly, old adults, aging. In the selection of studies
      the following inclusion criteria were used: original articles in English,
      Portuguese and Spanish languages. All selection and evaluation processes of the
      articles were performed by peers and the quality was verified by the Downs and
      Black scale. Twenty-one studies were included. The year of publication ranged
      from 2003 to 2014 and the size of the sample varied from 8 to 311 elderly
      subjects, aged at least 60 years old. The intervention period was from 4 weeks to
      12 months of Pilates exercise practice. It was concluded that despite the studies
      pointing to physical and motor benefits of the Pilates method in the elderly, we
      cannot state whether or not the method is effective, in view of the poor
      methodological quality of the studies included in this review.

PMID- 27020845
TI  - Energy intake highs and lows: how much does consistency matter in weight control?
AB  - Behavioural weight control programmes recommend adherence to daily energy intake
      goals, yet also allow for flexibility in intake across days. Evidence is lacking
      as to whether intake consistency is important for weight control. The current
      study explored the relation between day-to-day intake consistency and weight loss
      in the context of behavioural weight loss treatment and examined the relationship
      between variability in intake and several factors known to be associated with
      weight control success. Participants (N =  283) enrolled in a 12-month
      behavioural weight loss programme completed 24-h recalls of dietary intake and
      psychological measures. At the end of treatment, low intake variability and
      greater weight loss were associated, but variability was not predictive of weight
      loss independent of mean intake in continuous analyses. Interestingly,
      participants who met the programme goal of >=10% weight loss had less intake
      variability compared to those who lost <10%, although groups did not differ
      significantly on mean intake. Results suggest that daily intake consistency may
      facilitate successful weight loss for some. Additionally, autonomous motivation
      for weight management and cognitive dietary restraint were inversely related to
      end-of-treatment intake variability. Additional research is needed to examine
      whether recommendations to limit intake variability during behavioural weight
      loss treatment improve long-term weight control. 

PMID- 27020847
TI  - Sub-10 nm Silicon Nanopillar Fabrication Using Fast and Brushless Thermal
      Assembly of PS-b-PDMS Diblock Copolymer.
AB  - A new approach to obtaining spherical nanodomains using polystyrene-block
      polydimethylsiloxane (PS-b-PDMS) is proposed. To reduce drastically the process
      time, we blended a copolymer with cylindrical morphology with a PS homopolymer.
      Adding PS homopolymer into a low-molar-mass cylindrical morphology PS-b-PDMS
      system drives it toward a spherical morphology. Besides, by controlling the as
      spun state, spherical PDMS nanodomains could be kept and thermally arranged. This
      PS-homopolymer addition allows not only an efficient, purely thermal arrangement
      process of spheres but also the ability to work directly on nontreated silicon
      substrates. Indeed, as shown by STEM measurements, no PS brush surface treatment
      was necessary in our study to avoid a PDMS wetting layer at the interface with
      the Si substrate. Our approach was compared to a sphere-forming diblock
      copolymer, which needs a longer thermal annealing. Furthermore, GISAXS
      measurements provided complete information on PDMS sphere features. Excellent
      long-range order spherical microdomains were therefore produced on flat surfaces
      and inside graphoepitaxy trenches with a period of 21 nm, as were in-plane
      spheres with a diameter of 8 nm with a 15 min thermal annealing. Finally, direct
      plasma-etching transfer into the silicon substrate was demonstrated, and 20 nm
      high silicon nanopillars were obtained, which are very promising results for
      various nanopatterning applications. 

PMID- 27020848
TI  - A recombinant Sp185/333 protein from the purple sea urchin has multitasking
      binding activities towards certain microbes and PAMPs.
AB  - The purple sea urchin, Strongylocentrotus purpuratus, possesses a sophisticated
      innate immune system that responds to microbes effectively by swift expression of
      the highly diverse Sp185/333 gene family. The Sp185/333 proteins are predicted to
      have anti-pathogen functions based on inducible gene expression and their
      significant sequence diversity. Sp185/333 proteins are all predicted to be
      intrinsically disordered and do not exhibit sequence similarities to other known
      proteins. To test the anti-pathogen hypothesis, a recombinant Sp185/333 protein,
      rSp0032, was evaluated and found to exhibit specific binding to marine Vibrio
      diazotrophicus and to Saccharomyces cerevisiae, but not to two Bacillus species.
      rSp0032 also binds to LPS, beta-1,3-glucan and flagellin but not to
      peptidoglycan. rSp0032 binding to LPS can be competed by LPS, beta-1,3-glucan and
      flagellin but not by peptidoglycan. We speculate that the predicted intrinsically
      disordered structure of rSp0032 may adapt to different conformations in binding
      to a limited number of PAMPs and pathogens. Given that rSp0032 binds to a range
      of targets, and that up to 260 different Sp185/333 proteins can be expressed per
      individual sea urchin, this family of immune response proteins may facilitate
      effective host protection against a broad array of potential pathogens
      encountered in the marine environment.

PMID- 27020849
TI  - Phase diagrams of diblock copolymers in electric fields: a self-consistent field
      theory study.
AB  - We investigated the phase diagrams of diblock copolymers in external
      electrostatic fields by using real-space self-consistent field theory. The
      lamella, cylinder, sphere, and ellipsoid structures were observed and analyzed by
      their segment distributions, which were arranged to two types of phase diagrams
      to examine the phase behavior in weak and strong electric fields. One type was
      constructed on the basis of Flory-Huggins interaction parameter and volume
      fraction. We identified an ellipsoid structure with a body-centered cuboid
      arrangement as a stable phase and discussed the shift of phase boundaries in the
      electric fields. The other type of phase diagrams was established on the basis of
      the dielectric constants of two blocks in the electric fields. We then determined
      the regions of ellipsoid phase in the phase diagrams to examine the influence of
      dielectric constants on the phase transition between ellipsoidal and hexagonally
      packed cylinder phases. A general agreement was obtained by comparing our results
      with those described in previous experimental and theoretical studies. 

PMID- 27020851
TI  - Pathophysiology of humeral fractures in a sample of dairy heifers.
AB  - AIMS: To investigate the pathophysiology of humeral fractures in first-lactation
      dairy heifers in the North Island of New Zealand. METHODS: Ten 2-year-old dairy
      heifers with humeral fractures were subject to euthanasia and the fractured and
      non-fractured contralateral humeri were collected. Humeri were also collected
      from 10 unaffected 2-year-old dairy heifers sent for slaughter. Humeri from
      heifers with and without fractures were examined using computed tomography (CT),
      and four slices of the diaphysis and lower metaphysis (D1-4) were analysed using
      the Bone J plug-in for Image J. The humeri were sectioned sagittally and 5 mm
      bone slabs were processed for histopathology. RESULTS: There were no differences
      in bone length between the humeri from heifers with or without fractures
      (p=0.31). Median cortical bone mineral density at D1 was increased in humeri from
      affected compared with unaffected heifers (810 vs. 783 mg/cm(3); p=0.03),
      cortical area at D1 was reduced (816 vs. 1,037 mm(2); p=0.04), the median stress
      strain index, a calculated theoretical measure of bone strength, at D1 was
      decreased (7,288 vs. 9,072 mm(3); p<0.01), and the median ratio of overall bone
      volume (BV) to total volume (TV) was decreased (0.32 vs. 0.38; p<0.01). The
      median periosteal circumference at D1 was also reduced in humeri from affected
      compared with unaffected heifers (151 vs. 173 mm; p<0.01). Using a binary
      logistic regression model, BV/TV was the only variable associated with humeral
      fractures (p=0.03).In nine of 10 fractured humeri the fracture appeared to have
      started just distal to the head of the humerus and spiralled distally down the
      diaphysis to end just above the humeral condyles. Histopathological findings
      included a reduction in the number, and thickness, of trabeculae in the
      metaphysis; metaphyseal growth arrest lines, and osteoclastic resorption in
      fractured humeri. Concentrations of copper in serum from four of five animals
      with fractures were within, and one was below, normal reference ranges, while
      concentration of copper in the livers of three heifers with fractures were below
      adequate ranges. CONCLUSIONS: The CT and histological findings were consistent
      with a diagnosis of osteoporosis. We propose that humeral fractures in dairy
      heifers are associated with osteoporosis, possibly as a result of insufficient
      deposition of bone during growth because of protein-calorie malnutrition.
      Increased osteoclastic resorption of bone associated with calcium mobilisation
      for lactation, and periods of copper deficiency may contribute to bone weakening.

PMID- 27020850
TI  - The impact of acute stress on hormones and cytokines, and how their recovery is
      affected by music-evoked positive mood.
AB  - Stress and recovery from stress significantly affect interactions between the
      central nervous system, endocrine pathways, and the immune system. However, the
      influence of acute stress on circulating immune-endocrine mediators in humans is
      not well known. Using a double-blind, randomized study design, we administered a
      CO2 stress test to n = 143 participants to identify the effects of acute stress,
      and recovery from stress, on serum levels of several mediators with immune
      function (IL-6, TNF-alpha, leptin, and somatostatin), as well as on
      noradrenaline, and two hypothalamic-pituitary-adrenal axis hormones (ACTH and
      cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these
      serum parameters, and administered an auditory mood-induction protocol with
      positive music and a neutral control stimulus. The acute stress elicited
      increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels.
      Noradrenaline and ACTH exhibited the fastest and strongest stress responses,
      followed by cortisol, IL-6 and leptin. The music intervention was associated with
      more positive mood, and stronger cortisol responses to the acute stressor in the
      music group. Our data show that acute (CO2) stress affects endocrine, immune and
      metabolic functions in humans, and they show that mood plays a causal role in the
      modulation of responses to acute stress.

PMID- 27020852
TI  - Inhibition of Activin Signaling Slows Progression of Polycystic Kidney Disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD), characterized by the
      formation of numerous kidney cysts, is caused by PKD1 or PKD2 mutations and
      affects 0.1% of the population. Although recent clinical studies indicate that
      reduction of cAMP levels slows progression of PKD, this finding has not led to an
      established safe and effective therapy for patients, indicating the need to find
      new therapeutic targets. The role of TGF-beta in PKD is not clearly understood,
      but nuclear accumulation of phosphorylated SMAD2/3 in cyst-lining cells suggests
      the involvement of TGF-beta signaling in this disease. In this study, we ablated
      the TGF-beta type 1 receptor (also termed activin receptor-like kinase 5) in
      renal epithelial cells of PKD mice, which had little to no effect on the
      expression of SMAD2/3 target genes or the progression of PKD. Therefore, we
      investigated whether alternative TGF-beta superfamily ligands account for SMAD2/3
      activation in cystic epithelial cells. Activins are members of the TGF-beta
      superfamily and drive SMAD2/3 phosphorylation via activin receptors, but activins
      have not been studied in the context of PKD. Mice with PKD had increased
      expression of activin ligands, even at early stages of disease. In addition,
      treatment with a soluble activin receptor IIB fusion (sActRIIB-Fc) protein, which
      acts as a soluble trap to sequester activin ligands, effectively inhibited cyst
      formation in three distinct mouse models of PKD. These data point to activin
      signaling as a key pathway in PKD and a promising target for therapy.

PMID- 27020853
TI  - Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal Allografts.
AB  - Despite advances in immunosuppression, antibody-mediated rejection is a serious
      threat to allograft survival. Alloreactive memory helper T cells can induce
      potent alloantibody responses and often associate with poor graft outcome.
      Nevertheless, the ability of memory T cells to elicit well characterized
      manifestations of antibody-mediated rejection has not been tested. We
      investigated helper functions of memory CD4 T cells in a mouse model of renal
      transplantation. Whereas the majority of unsensitized C57Bl/6 recipients
      spontaneously accepted fully MHC-mismatched A/J renal allografts, recipients
      containing donor-reactive memory CD4 T cells rapidly lost allograft function.
      Increased serum creatinine levels, high serum titers of donor-specific
      alloantibody, minimal T cell infiltration, and intense C4d deposition in the
      grafts of sensitized recipients fulfilled all diagnostic criteria for acute renal
      antibody-mediated rejection in humans. IFNgamma neutralization did not prevent
      the renal allograft rejection induced by memory helper T cells, and CD8 T cell
      depletion at the time of transplantation or depletion of both CD4 and CD8 T cells
      also did not prevent the renal allograft rejection induced by memory helper T
      cells starting at day 4 after transplantation. However, B cell depletion
      inhibited alloantibody generation and significantly extended allograft survival,
      indicating that donor-specific alloantibodies (not T cells) were the critical
      effector mechanism of renal allograft rejection induced by memory CD4 T cells.
      Our studies provide direct evidence that recipient T cell sensitization may
      result in antibody-mediated rejection of renal allografts and introduce a
      physiologically relevant animal model with which to investigate mechanisms of
      antibody-mediated rejection and novel therapeutic approaches for its prevention
      and treatment.

PMID- 27020854
TI  - Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct
      Cells.
AB  - Extracellular vesicles (ECVs) facilitate intercellular communication along the
      nephron, with the potential to change the function of the recipient cell.
      However, it is not known whether this is a regulated process analogous to other
      signaling systems. We investigated the potential hormonal regulation of ECV
      transfer and report that desmopressin, a vasopressin analogue, stimulated the
      uptake of fluorescently loaded ECVs into a kidney collecting duct cell line
      (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from
      cells overexpressing microRNA-503 led to downregulated expression of microRNA-503
      target genes, but only in the presence of desmopressin. Mechanistically, ECV
      entry into mCCDC11 cells required cAMP production, was reduced by inhibiting
      dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we
      measured the urinary excretion and tissue uptake of fluorescently loaded ECVs
      delivered systemically to mice before and after administration of the vasopressin
      V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of
      administered ECVs in the urine; tolvaptan increased recovery five-fold and
      reduced ECV deposition in kidney tissue. Furthermore, in a patient with central
      diabetes insipidus, desmopressin reduced the excretion of ECVs derived from
      glomerular and proximal tubular cells. These data are consistent with vasopressin
      regulated uptake of ECVs in vivo We conclude that ECV uptake is a specific and
      regulated process. Physiologically, ECVs are a new mechanism of intercellular
      communication; therapeutically, ECVs may be a vehicle by which RNA therapy could
      be targeted to specific cells for the treatment of kidney disease.

PMID- 27020855
TI  - Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
AB  - Gain-of-function mutations of classic transient receptor potential channel 6
      (TRPC6) were identified in familial FSGS, and increased expression of wild-type
      TRPC6 in glomeruli is observed in several human acquired proteinuric diseases.
      Synaptopodin, an actin binding protein that is important in maintaining podocyte
      function, is downregulated in various glomerular diseases. Here, we investigated
      whether synaptopodin maintains podocyte function by regulating podocyte surface
      expression and activity of TRPC6. We show indirect interaction and nonrandom
      association of synaptopodin and TRPC6 in podocytes. Knockdown of synaptopodin in
      cultured mouse podocytes increased the expression of TRPC6 at the plasma
      membrane, whereas overexpression of synaptopodin decreased it. Mechanistically,
      synaptopodin-dependent TRPC6 surface expression required functional actin and
      microtubule cytoskeletons. Overexpression of wild-type or FSGS-inducing mutant
      TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx
      and induced apoptosis. In vivo, knockdown of synaptopodin also caused increased
      podocyte surface expression of TRPC6. Administration of cyclosporin A, which
      stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild
      type mice but to a lesser extent in TRPC6 knockout mice. Furthermore,
      administration of cyclosporin A reversed the LPS-induced increase in podocyte
      surface expression of TRPC6 in wild-type mice. Our findings suggest that
      alteration in synaptopodin levels under disease conditions may modify
      intracellular TRPC6 channel localization and activity, which further contribute
      to podocyte dysfunction. Reducing TRPC6 surface levels may be a new approach to
      restoring podocyte function.

PMID- 27020856
TI  - Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria.
AB  - Changes in metabolite levels of the kynurenine pathway have been observed in
      patients with CKD, suggesting involvement of this pathway in disease
      pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine
      3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with
      albuminuria. This study investigated this association in more detail. We compared
      KMO abundance in the glomeruli of mice and humans under normal and diabetic
      conditions, observing a decrease in glomerular KMO expression with diabetes.
      Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each
      led to a proteinuria phenotype. We observed pronounced podocyte foot process
      effacement on long stretches of the filtration barrier in the zebrafish knockdown
      model and mild podocyte foot process effacement in the mouse model, whereas all
      other structures within the kidney remained unremarkable. These data establish
      the candidacy of KMO as a causal factor for changes in the kidney leading to
      proteinuria and indicate a functional role for KMO and metabolites of the
      tryptophan pathway in podocytes.

PMID- 27020857
TI  - Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in Estrogen
      Receptor-Positive Breast Cancer.
AB  - Small-molecule inhibitors of the CDK4/6 cell-cycle kinases have shown clinical
      efficacy in estrogen receptor (ER)-positive metastatic breast cancer, although
      their cytostatic effects are limited by primary and acquired resistance. Here we
      report that ER-positive breast cancer cells can adapt quickly to CDK4/6
      inhibition and evade cytostasis, in part, via noncanonical cyclin D1-CDK2
      mediated S-phase entry. This adaptation was prevented by cotreatment with hormone
      therapies or PI3K inhibitors, which reduced the levels of cyclin D1 (CCND1) and
      other G1-S cyclins, abolished pRb phosphorylation, and inhibited activation of S
      phase transcriptional programs. Combined targeting of both CDK4/6 and PI3K
      triggered cancer cell apoptosis in vitro and in patient-derived tumor xenograft
      (PDX) models, resulting in tumor regression and improved disease control.
      Furthermore, a triple combination of endocrine therapy, CDK4/6, and PI3K
      inhibition was more effective than paired combinations, provoking rapid tumor
      regressions in a PDX model. Mechanistic investigations showed that acquired
      resistance to CDK4/6 inhibition resulted from bypass of cyclin D1-CDK4/6
      dependency through selection of CCNE1 amplification or RB1 loss. Notably,
      although PI3K inhibitors could prevent resistance to CDK4/6 inhibitors, they
      failed to resensitize cells once resistance had been acquired. However, we found
      that cells acquiring resistance to CDK4/6 inhibitors due to CCNE1 amplification
      could be resensitized by targeting CDK2. Overall, our results illustrate
      convergent mechanisms of early adaptation and acquired resistance to CDK4/6
      inhibitors that enable alternate means of S-phase entry, highlighting strategies
      to prevent the acquisition of therapeutic resistance to these agents. Cancer Res;
      76(8); 2301-13. (c)2016 AACR.

PMID- 27020858
TI  - NRF2 Intensifies Host Defense Systems to Prevent Lung Carcinogenesis, but After
      Tumor Initiation Accelerates Malignant Cell Growth.
AB  - Nrf2 activation promotes resistance to chemical carcinogenesis in animal models,
      but activating mutations in Nrf2 also confer malignant characters to human cells
      by activating antioxidative/detoxifying enzymes and metabolic reprogramming. In
      this study, we examined how these contradictory activities of Nrf2, cancer
      chemoprevention and cancer cell growth enhancement, can be reconciled in an
      established mouse model of urethane-induced lung carcinogenesis. Using Keap1
      knockdown (kd) mice, which express high levels of Nrf2, we found that urethane
      was rapidly excreted into the urine, consistent with an upregulation in the
      expression of urethane detoxification genes. Consequently, urethane-induced
      tumors were significantly smaller and less frequent in Keap1-kd mice than in wild
      type mice. In contrast, tumor cells derived from Keap1-kd mice and transplanted
      into nude mice exhibited higher tumorigenicity compared with cells derived from
      wild-type mice. To identify the factors contributing to the tumor growth
      phenotype in the transplantation model, we performed a microarray analysis and
      found that many antioxidative stress genes were upregulated in the Keap1-kd
      derived tumors. Therefore, we suggest that Nrf2 activation in cancer cells
      enhances their tumorigenicity, but global Nrf2 activation, as in Keap1-kd mice,
      simultaneously enhances anticancer immunity, thereby suppressing the growth
      potential of Keap1-kd tumors. Our findings provide relevant insight into the dual
      role of Nrf2 in cancer and warrant further studies of Nrf2 function during
      different stages of carcinogenesis. Cancer Res; 76(10); 3088-96. (c)2016 AACR.

PMID- 27020859
TI  - PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive
      Character of PTEN-Deficient Prostate Cancers.
AB  - Diet affects the risk and progression of prostate cancer, but the interplay
      between diet and genetic alterations in this disease is not understood. Here we
      present genetic evidence in the mouse showing that prostate cancer progression
      driven by loss of the tumor suppressor Pten is mainly unresponsive to a high-fat
      diet (HFD), but that coordinate loss of the protein tyrosine phosphatase Ptpn1
      (encoding PTP1B) enables a highly invasive disease. Prostate cancer in Pten(-/
      )Ptpn1(-/-) mice was characterized by increased cell proliferation and Akt
      activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation
      upon HFD feeding. Prostate-specific overexpression of PTP1B was not sufficient to
      initiate prostate cancer, arguing that it acted as a diet-dependent modifier of
      prostate cancer development in Pten(-/-) mice. Our findings offer a preclinical
      rationale to investigate the anticancer effects of PTP1B inhibitors currently
      being studied clinically for diabetes treatment as a new modality for management
      of prostate cancer. Cancer Res; 76(11); 3130-5. (c)2016 AACR.

PMID- 27020860
TI  - CD27 Agonism Plus PD-1 Blockade Recapitulates CD4+ T-cell Help in Therapeutic
      Anticancer Vaccination.
AB  - While showing promise, vaccination strategies to treat cancer require further
      optimization. Likely barriers to efficacy involve cancer-associated
      immunosuppression and peripheral tolerance, which limit the generation of
      effective vaccine-specific cytotoxic T lymphocytes (CTL). Because CD4(+) T cells
      improve CTL responsiveness, next-generation vaccines include helper epitopes.
      Here, we demonstrate in mice how CD4(+) T-cell help optimizes the CTL response to
      a clinically relevant DNA vaccine engineered to combat human papillomavirus
      expressing tumors. Inclusion of tumor-unrelated helper epitopes greatly increased
      CTL priming, effector, and memory T-cell programming. CD4(+) T-cell help
      optimized the CTL response in all these aspects via CD27/CD70 costimulation.
      Notably, administration of an agonistic CD27 antibody could largely replace
      helper epitopes in promoting primary and memory CTL responses, acting directly on
      CD8(+) T cells. CD27 agonism improved efficacy of the vaccine without helper
      epitopes, more so than combined PD-1 and CTLA-4 blockade. Combining CD27 agonism
      with CTLA-4 blockade improved vaccine-induced CTL priming and tumor infiltration,
      but only combination with PD-1 blockade was effective at eradicating tumors,
      thereby fully recapitulating the effect of CD4(+) T-cell help on vaccine
      efficacy. PD-1 blockade alone did not affect CTL priming or tumor infiltration,
      so these results implied that it cooperated with CD4(+) T-cell help by
      alleviating immune suppression against CTL in the tumor. Helper epitope inclusion
      or CD27 agonism did not stimulate regulatory T cells, and vaccine efficacy was
      also improved by CD27 agonism in the presence of CD4(+) T-cell help. Our findings
      provide a preclinical rationale to apply CD27 agonist antibodies, either alone or
      combined with PD-1 blockade, to improve the therapeutic efficacy of cancer
      vaccines and immunotherapy generally. Cancer Res; 76(10); 2921-31. (c)2016 AACR.

PMID- 27020861
TI  - AMPK Activation and Metabolic Reprogramming by Tamoxifen through Estrogen
      Receptor-Independent Mechanisms Suggests New Uses for This Therapeutic Modality
      in Cancer Treatment.
AB  - Tamoxifen is the most widely used adjuvant chemotherapeutic for the treatment of
      estrogen receptor (ER)-positive breast cancer, yet a large body of clinical and
      preclinical data indicates that tamoxifen can modulate multiple cellular
      processes independently of ER status. Here, we describe the ER-independent
      effects of tamoxifen on tumor metabolism. Using combined pharmacologic and
      genetic knockout approaches, we demonstrate that tamoxifen inhibits oxygen
      consumption via inhibition of mitochondrial complex I, resulting in an increase
      in the AMP/ATP ratio and activation of the AMP-activated protein kinase (AMPK)
      signaling pathway in vitro and in vivo AMPK in turn promotes glycolysis and
      alters fatty acid metabolism. We also show that tamoxifen-induced cytotoxicity is
      modulated by isoform-specific effects of AMPK signaling, in which AMPKalpha1
      promotes cell death through inhibition of the mTOR pathway and translation. By
      using agents that concurrently target distinct adaptive responses to tamoxifen
      mediated metabolic reprogramming, we demonstrate increased cytotoxicity through
      synergistic therapeutic approaches. Our results demonstrate novel metabolic
      perturbations by tamoxifen in tumor cells, which can be exploited to expand the
      therapeutic potential of tamoxifen treatment beyond ER(+) breast cancer. Cancer
      Res; 76(11); 3295-306. (c)2016 AACR.

PMID- 27020862
TI  - AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER
      Positive and ESR1-Mutant Breast Tumors in Preclinical Models.
AB  - Fulvestrant is an estrogen receptor (ER) antagonist administered to breast cancer
      patients by monthly intramuscular injection. Given its present limitations of
      dosing and route of administration, a more flexible orally available compound has
      been sought to pursue the potential benefits of this drug in patients with
      advanced metastatic disease. Here we report the identification and
      characterization of AZD9496, a nonsteroidal small-molecule inhibitor of ERalpha,
      which is a potent and selective antagonist and downregulator of ERalpha in vitro
      and in vivo in ER-positive models of breast cancer. Significant tumor growth
      inhibition was observed as low as 0.5 mg/kg dose in the estrogen-dependent MCF-7
      xenograft model, where this effect was accompanied by a dose-dependent decrease
      in PR protein levels, demonstrating potent antagonist activity. Combining AZD9496
      with PI3K pathway and CDK4/6 inhibitors led to further growth-inhibitory effects
      compared with monotherapy alone. Tumor regressions were also seen in a long-term
      estrogen-deprived breast model, where significant downregulation of ERalpha
      protein was observed. AZD9496 bound and downregulated clinically relevant ESR1
      mutants in vitro and inhibited tumor growth in an ESR1-mutant patient-derived
      xenograft model that included a D538G mutation. Collectively, the pharmacologic
      evidence showed that AZD9496 is an oral, nonsteroidal, selective estrogen
      receptor antagonist and downregulator in ER(+) breast cells that could provide
      meaningful benefit to ER(+) breast cancer patients. AZD9496 is currently being
      evaluated in a phase I clinical trial. Cancer Res; 76(11); 3307-18. (c)2016 AACR.

PMID- 27020863
TI  - A comparison of the performance of the Braden Q and the Glamorgan paediatric
      pressure ulcer risk assessment scales in general and intensive care paediatric
      and neonatal units.
AB  - AIMS: To compare the predictive ability of two risk assessment scales used in
      children. BACKGROUND: There are several risk assessment scales (RASs) employed in
      paediatric settings but most have been modified from adult scales such as the
      Braden Q whereas the Glamorgan was an example of a scale designed for children.
      METHODS: Using incidence data from 513 paediatric hospital admissions, receiver
      operating characteristic (ROC) was employed to compare the two scales. The area
      under the curve (AUC) was the outcome of interest. RESULTS: The two scales were
      similar in this population in terms of area under the curve. Neonatal and
      paediatric intensive care were similar in terms of AUC for both scales but in
      general paediatric wards the Braden Q may be superior in predicting risk.
      CONCLUSION: Either scale could be used if the predictive ability was the outcome
      of interest. The scales appear to work well with neonatal, paediatric intensive
      care and general children's wards. However the Glamorgan scale is probably
      preferred by childrens' nurses as it is easy to use and designed for use in
      children. There is some suggestion that while the two scales are similar in
      intensive care, for general paediatrics the Braden Q may be the better scale.

PMID- 27020864
TI  - Introduction to skin aging.
AB  - Cutaneous science has seen considerable development in the last 25 years, in part
      due to the Omics revolution, and the appreciation that this organ is hardwired
      into the body's key neuro-immuno-endocrine axes. Moreover, there is greater
      appreciation of how stratification of skin disorders will permit more targeted
      and more effective treatments. Against this has been how the remarkable extension
      in the average human life-span, though in the West at least, this parallels
      worrying increases in lifestyle-associated conditions like diabetes, skin cancer
      etc. These demographic trends bring greater urgency to finding clinical solutions
      for numerous age-related deficits in skin function caused by extrinsic and
      intrinsic factors. Mechanisms for aging skin include the actions of reactive
      oxygen species (ROS), mtDNA mutations, and telomere shortening, as well as
      hormonal changes. We have also significantly improved our understanding of how to
      harness the skin's considerable regenerative capacity e.g., via its remarkable
      investment of stem cell subpopulations. In this way we hope to develop new
      strategies to selectively target the skin's capacity to undergo optimal wound
      repair and regeneration. Here, the unsung hero of the skin regenerative power may
      be the humble hair follicle, replete with its compliment of epithelial,
      mesenchymal, neural and other stem cells. This review introduces the topic of
      human skin aging, with a focus on how maintenance of function in this complex
      multi-cell type organ is key for retaining quality of life into old age.

PMID- 27020865
TI  - Effects of zearalenone-diet on expression of ghrelin and PCNA genes in ovaries of
      post-weaning piglets.
AB  - Numerous reports have provided evidence that zearalenone (ZEN) can increase the
      weight of genital organs. These findings have been confirmed by many studies in
      which the ghrelin gene was expressed in the ovary and was implicated in the
      control of cells in reproductive tissues. The proliferating cell nuclear antigen
      (PCNA) is an important marker of cell proliferation. The present study
      investigates the effects of a ZEN-treated diet on the development of ovaries in
      post-weaning piglets by the detection of ghrelin and PCNA protein and relative
      abundance of mRNA using optical microscopy, immunohistochemistry and quantitative
      real-time (qRT-PCR). A total of 20 piglets (Duroc * Landrace * Yorkshire) weaned
      at 28 d, with an average body weight of 8.74 +/- 0.26 kg (P=0.919) were used in
      this study. Piglets in the control group (n=10) were fed a normal basal diet, and
      those in the treatment group (n=10) were fed a diet containing ZEN (1.04 mg/kg),
      for 35 d. The proportion of growing follicles and diameter of the largest growing
      follicle in ovaries were greater in piglets fed the diet with ZEN. The total
      integrated optical densities of protein and mRNA of ghrelin and PCNA were greater
      with the feeding of the ZEN-treatment diet. The results suggested that 1.04 mg/kg
      ZEN could promote the autocrine action or expression of the ghrelin gene in
      piglet ovary, and further accelerate the development of ovaries (follicles).

PMID- 27020866
TI  - IL-12 Family Cytokines: General Characteristics, Pathogenic Microorganisms,
      Receptors, and Signalling Pathways.
AB  - Among a wide range of cytokines, the Interleukin 12 (IL-12) family has its unique
      structural, functional, and immunological characteristics that have made this
      family as important immunological playmakers. Because of the importance of IL-12
      heterodimeric cytokines in microbial infections, autoimmune diseases, and
      cancers, the authors of this literature discuss about the general characteristics
      of IL-12 family members, the interactions between IL-12 cytokines and pathogenic
      microorganisms, the interleukins receptors and their strategies for selecting
      different signalling pathways. IL-12 and IL-23 are similar in p40 subunits and
      both are involved in proinflammatory responses while, IL-27 and IL-35 contribute
      to anti-inflammatory activities; however, IL-27 is also involved in pro
      inflammatory responses. There are some similarities and dissimilarities among IL
      12 family members which make them a unique bridge between innate and adaptive
      immune systems. The bioactivities of IL-12 family indicate a brilliant promise
      for their applications in different fields of medicine. The members of IL-12
      family are candidate for several therapeutics including gene therapy, cancer
      therapy, tumour therapy, and vaccination. To have an accurate diagnostic
      technique and definite treatment regarding to infectious diseases, the playmakers
      of IL-12 family as effective criteria together with microarray technology are the
      best choices for current and future applications. 

PMID- 27020867
TI  - Antimicrobial Activity and Phylogenetic Analysis of Streptomyces Parvulus Dosmb
      D105 Isolated from the Mangrove Sediments of Andaman Islands.
AB  - Actinomycetes, especially species of Streptomyces are prolific producers of
      pharmacologically significant compounds accounting for about 70% of the naturally
      derived antibiotics that are presently in clinical use. In this study, we used
      five solvents to extract the secondary metabolites from marine Streptomyces
      parvulus DOSMB-D105, which was isolated from the mangrove sediments of the South
      Andaman Islands. Among them, ethyl acetate crude extract showed maximum activity
      against 11 pathogenic bacteria and six fungi. Presence of bioactive compounds in
      the ethyl acetate extract was determined using GC-MS and the compounds detected
      in the ethyl acetate extract were matched with the National Institute of
      Standards and Technology (NIST) library. Totally eight compounds were identified
      and the prevalent compounds were 2 steroids, 2 alkaloids, 2 plasticizers, 1
      phenolic and 1 alkane. Present study revealed that S. parvulus DOSMB-D105 is a
      promising species for the isolation of valuable bioactive compounds to combat
      pathogenic microbes. 

PMID- 27020868
TI  - Serum Neopterin and Procalcitonin Levels in Relationship with Pediatric Burn
      Wound Infections.
AB  - Infection and septic complications in burn patients can be monitored by
      procalcitonin (PCT) and neopterin plasma values. The aim of the study was to
      investigate serum neopterin and PCT levels with WBC (white blood cell) and CRP (C
      reactive protein) levels in patient group (PG) and healthy control group (HCG)
      and to investigate the relationship of these markers with burn wound infections
      (BWI). As the PG, 23 patients between 0-12 ages and up to 30% Total Body Surface
      Area (TBSA) burned and 15 HCG were included. PCT, neopterin, WBC, and CRP results
      on the first, the seventh, the fourteenth and the 21st day have been compared.
      During the follow-up period, 11 patients with BWI and 12 patients without BWI
      were classified as infected and non-infected patients, respectively. PCT and
      neopterin levels were detected higher in patients with BWI but no significant
      difference were present. Also, PCT and neopterin levels within the first 24 hours
      following the burn were detected higher in PG than HCG. CRP and WBC levels were
      detected high due to burn trauma. PCT and neopterin levels were increased in
      patients with BWI. PCT levels were increased during the pre-infectious period,
      while neopterin levels increased during the post-infectious period. 

PMID- 27020869
TI  - Does Staphylococcus Saprophyticus Cause Acute Cystitis only in Young Females, or
      is there more to the Story? A One-Year Comprehensive Study Done in Budapest,
      Hungary.
AB  - Staphylococcus saprophyticus is a well-known urinary pathogen in acute cystitis
      in young females. We completed a retrospective overview of the distribution of
      urinary tract infections (UTIs) occurring in 2014, at Semmelweis University
      hospitals and at Heim Pal Children's Hospital. Six age-groups (ages 0-100) were
      examined, with the frequency of S. saprophyticus in females being: 0.1% (0-4),
      0.7%, (5-15), 7.4% (16-24), 1.2% (25-39), 0.4% (40-59) and 0.1% (60-100), and S.
      saprophyticus being the 3(rd) most common pathogen in females aged 16-24. In
      males, S. saprophyticus was only isolated from those aged 5-15. Seasonal
      distribution of UTIs caused by S. saprophyticus showed that most infections
      occurred during the months of January, June, August and November. Antibiotic
      resistance rates of amoxicillin, clindamycin, doxycycline, erythromycin,
      gentamicin and sulfamethoxazole- trimethoprim varied as follows: 0.9%, 32.7%,
      19.6%, 34.6%, 0.9% and 0.9%, respectively. Thirty randomly selected samples were
      analysed by pulsed-field gelelectrophoresis, and 28 different genotypes were
      identified. S. saprophyticus is involved in the pathogenesis of acute cystitis
      not only in young females, but also in other age-groups, and in young males as
      well. We did not find any significant seasonal occurrence in S. saprophyticus
      caused UTIs. The infective strains were genetically diverse. Antibiotic
      resistance does not pose any issue as of yet. 

PMID- 27020870
TI  - Comparison of Molecular and Phenotypic Methods for the Detection and
      Characterization of Carbapenem Resistant Enterobacteriaceae.
AB  - In recent years, there has been a rapid dissemination of carbapenem resistant
      Enterobacteriaceae (CRE). This study aimed to compare phenotypic and molecular
      methods for detection and characterization of CRE isolates at a large tertiary
      care hospital in Saudi Arabia. This study was carried out between January 2011
      and November 2013 at the King Khalid University Hospital (KKUH) in Saudi Arabia.
      Determination of presence of extended-spectrum beta-lactamases (ESBL) and
      carbapenem resistance was in accordance with Clinical and Laboratory Standards
      Institute (CLSI) guidelines. Phenotypic classification was done by the
      MASTDISCS(TM) ID inhibitor combination disk method. Genotypic characterization of
      ESBL and carbapenemase genes was performed by the Check-MDR CT102. Diversilab rep
      PCR was used for the determination of clonal relationship. Of the 883 ESBL
      positive Enterobacteriaceae detected during the study period, 14 (1.6%) isolates
      were carbapenem resistant. Both the molecular genotypic characterization and
      phenotypic testing were in agreement in the detection of all 8 metalo-beta
      lactamases (MBL) producing isolates. Of these 8 MBL-producers, 5 were positive
      for blaNDM gene and 3 were positive for blaVIM gene. Molecular method identified
      additional blaOXA gene isolates while MASTDISCS(TM) ID detected one AmpC producer
      isolate. Both methods agreed in identifying 2 carbapenem resistant isolates which
      were negative for carbapenemase genes. Diversilab rep-PCR analysis of the 9
      Klebsiella pneumoniae isolates revealed polyclonal distribution into eight
      clusters. MASTDISCS(TM) ID is a reliable simple cheap phenotypic method for
      detection of majority of carbapenemase genes with the exception of the blaOXA
      gene. We recommend to use such method in the clinical laboratory. 

PMID- 27020871
TI  - High Prevalence and Resistance Patterns of Community-Associated Methicillin
      Resistant Staphylococcus Aureus in the Pomoravlje Region, Serbia.
AB  - With a view to estimating the prevalence and resistance patterns of CA-MRSA in
      one region of Serbia, we performed an analysis of MRSA isolates from healthy
      people and hospitalised patients. The detection of CA-MRSA was carried out by
      SCCmec typing. In MRSA isolates from hospitalised patients SCCmec types IV and V
      were found in 76% of the strains. Similar percentage (80%) of CA-MRSA genotypes
      was present in healthy people. SCCmec type V harbouring MRSA was the most
      successful clone. Higher prevalence of type V in hospitalised patients to that in
      healthy people (70% vs 54%) may indicate nosocomial transmissions in at least
      some hospital units. All MRSA strains from hospitalised patients were resistant
      to one or more non-beta-lactam antibiotics while 52% were multi-resistant. In
      isolates from healthy people, 16% were sensitive to all non-beta-lactam
      antibiotics and 40% were multi-resistant. Similar percentage of multi-resistant
      CA- and HA-genotypes occurred in a particular environment (53% vs 50% in
      hospitalised patients, and 37.5% vs 37.5% in healthy people) indicating selective
      pressure of antibiotics as a leading force conferring antibiotic resistance. High
      prevalence of CA-MRSA and high resistance rate both in hospitals and the
      community suggest that this pathogen has been present in the Pomoravlje Region,
      central Serbia for years. 

PMID- 27020872
TI  - Association of IFN-gamma and P2X7 Receptor Gene Polymorphisms in Susceptibility
      to Tuberculosis Among Iranian Patients.
AB  - Interferon-gamma (IFN-gamma) and P2X7 receptor are crucial for host defence
      against mycobacterial infections. Recent studies have indicated that IFN-gamma,
      IFN-gamma receptor 1 (IFN-gammaR1) andP2X7 gene polymorphisms are associated with
      susceptibility to pulmonary tuberculosis (TB). However, the relationship between
      IFN-gamma and P2X7 polymorphism and TB susceptibility remains inconclusive in
      Iranian population. For this reason, single nucleotide polymorphisms (SNPs) in
      IFN-gamma (G+2109A), IFN-gammaR1 (G-611A) and P2X7 genes (at -762, 1513 position)
      in patients (n = 100) were assessed using PCR-RFLP. Data were analysed with SPSS
      version 18. For the 2109 loci of IFN-gamma gene, the frequency of mutant alleles
      between patients and controls were not statistically significant. However, there
      was a significant difference between the TB patient and controls for -611 alleles
      of IFN-gammaR1 (P = 0.01). Additionally, the frequency of P2X7 gene polymorphisms
      (SNP-762 and 1513) between patients and controls was statistically significant.
      In conclusions, our study revealed a significant association of IFN-gammaR1 and
      P2X7 genes polymorphisms with risk of developing TB in Iranian population. 

PMID- 27020873
TI  - Assessment of Periodontopathogens in Subgingival Biofilm of Banded and Bonded
      Molars in Early Phase of Fixed Orthodontic Treatment.
AB  - To assess the prevalence and occurrence of eleven periodontopathogens in
      subgingival biofilm of banded and bonded molars during the first period of fixed
      orthodontic treatment. Subjects were selected from patients referred to
      orthodontic treatment and were divided in two groups: group A comprised fifteen
      patients (14.4+/-2.45 years of age) who received orthodontic bands on first
      permanent molars and group B of ten patients (15.7+/-1.87 years of age) with
      directly bonded tubes on the labial surface of the same teeth. Subgingival sample
      collection was performed before bands and tubes application and 4-7 weeks after
      attachment placement. DNA-strip tehnique was used to assess the presence of
      eleven putative periodontopathogens at each time point. Fusobacterium nucleatum,
      Eikenella corrodens and Capnocytophaga spp. were found in a large number of
      samples, other periodontopathogens were present in a smaller rate. The 4-7 weeks
      after attachment placement a slight increase of putative species was observed in
      both groups. The presence of orthodontic tubes and bands influence the
      accumulation and composition of subgingival microbiota. Higher level of oral
      hygiene should be achieved before and during orthodontic treatment in order to
      prevent any side effects on periodontal tissues. 

PMID- 27020874
TI  - Seasonal and Spatial Changes of Planktonic Bacterial Communities Inhabiting the
      Natural Thermal Lake Heviz, Hungary.
AB  - Lake Heviz is a unique thermal spa located in Hungary. Owing to the thermal
      springs nourishing the lake, it has a relatively rapid water turnover. In spring
      2011 a comprehensive embankment reconstruction was performed to preserve the
      water supply of the surrounding wetland habitats. The physical and chemical
      parameters as well as the planktonic microbial communities were studied with
      special respect to the effect of the disturbance of the water of Lake Heviz.
      According to the abiotic components, both temporal and spatial differences were
      revealed with the exception of autumn samples. The reconstruction resulted in a
      short term but dramatic alteration of the total planktonic bacterial and
      cyanobacterial community structures as revealed by denaturing gradient gel
      electrophoresis. In addition, greater seasonal than spatial differences of
      bacterial communities were also observed. Planktonic bacterial community
      composition of Lake Heviz included mainly typical freshwater species within
      phylum Actinobacteria, Chloroflexi, Cyanobacteria and class Alpha-, Beta- and
      Gamma-proteobacteria. Most of them were aerobic or facultative anaerobic
      heterotrophic but chemolitotrophic (e.g. Thiobacillus) or photolithotrophic (e.g.
      Cyanobacteria and Chloroflexi) autotrophic microbes were also identified. 

PMID- 27020875
TI  - Contribution of the Kallikrein/Kinin System to the Mediation of ConA-Induced
      Inflammatory Ascites.
AB  - Intraperitoneal administration of concanavalin A (ConA, 25 mg/kg b.w.), a cell
      binding plant lectin was used for inducing inflammatory ascites, and potential
      inhibitors were tested in 1 h and 2.5 h experiments, i.e. still before the major
      influx of leucocytes. At the end of the experiment the peritoneal fluid was
      collected and measured. The ConA-induced ascites was significantly (p<0.01) and
      dose-dependently inhibited by icatibant (HOE-140), a synthetic polypeptide
      antagonist of bradykinin receptors. Aprotinin, a kallikrein inhibitor protein
      also had significant (p<0.01), but less marked inhibitory effect. L-NAME, an
      inhibitor of NO synthesis, and atropine methylnitrate, an anticholinergic
      compound, were ineffective. It is concluded, that the kallikrein/kinin system
      contributes to the mediation of the ConA-induced ascites by increasing
      subperitoneal vascular permeability, independent of the eventual vasodilation
      produced by NO. It is known, that membrane glycoproteins are aggregated by the
      tetravalent ConA and the resulting distortion of membrane structure may explain
      the activation of the labile prekallikrein. Complete inhibition of the ConA
      induced ascites could not be achieved by aprotinin or icatibant, which indicates
      the involvement of additional mediators. 

PMID- 27020876
TI  - Sperm membrane integrity in fresh and frozen-thawed canine semen samples: a
      comparison of vital stains with the NucleoCounter SP-100.
AB  - The objective of this study was to assess sperm membrane integrity in canine
      semen samples using three different vital stains and the NucleoCounter SP-100
      (NC). In addition, the occurrence of half-stained sperm heads, the influence of
      investigator, and storage-related artifacts using stained smears were examined.
      Forty fresh (30 dogs) and 40 frozen-thawed (28 dogs) canine semen samples were
      analyzed. The vital stains eosin (E), eosin-nigrosin (EN), and bromphenolblue
      nigrosin (BN) were compared. Two smears per stain were prepared and a total of
      200 sperm per slide were classified using bright field microscopy. Each slide was
      examined twice by three investigators. Spermatozoa with completely red (E, EN) or
      blue (BN) stained sperm heads were classified as "dead". Half-stained sperm heads
      were counted separately. Sperm concentration and viability were determined using
      the NC. The NC works with a built-in fluorescence microscope using propidium
      iodide as a fluorescence dye. Statistical analysis for comparison of results was
      made using mean values with standard deviation, Bland-Altman plot and coefficient
      of variation (CV). Staining with E led to a significant higher percentage of dead
      sperm compared with EN and BN (P < 0.05), which gave comparable results. Vital
      stains revealed higher CVs (range 8.8%-32.1%) than the NC (<6.5%). Interobserver
      viability ranged from 17.5% to 45.4% and was within the same range between
      stains. If only completely stained sperm heads were considered, best agreement
      was found between the E and the NC. In case of EN and BN, inclusion of half
      stained sperm heads reduced the difference compared with NC. In general, the
      agreement between methods was better in samples with a low percentage of dead
      spermatozoa. In smears of fresh semen stored up to 3 months, no increase in the
      percentage of dead spermatozoa could be observed. In some smears of frozen-thawed
      samples stained with E (n = 12) or BN (n = 2), all previously unstained
      spermatozoa were additionally stained during storage. In conclusion, all vital
      stains examined in this study technically can be used for differentiation between
      live and dead spermatozoa in canine semen samples, but the relatively high CVs
      have to be kept in mind. It is recommended to examine smears of frozen-thawed
      semen soon after preparation. Half-stained sperm heads should be counted as live
      sperm in E-stained smears. The NC allows assessment of sperm concentration and
      viability with a reasonable repeatability. 

PMID- 27020877
TI  - Developmental competence and cryotolerance of caprine parthenogenetic embryos
      cultured in chemically defined media.
AB  - In animal reproduction technologies, the in vitro embryo culture system has
      advanced over the past few decades. However, in vitro cultured embryos still have
      reduced functional and physiological abilities compared with those from in vivo
      conditions, and many factors of oviduct and uterine environments have not yet
      been revealed. Here, we demonstrated the in vitro culture of domestic goat (Capra
      hircus) embryos using two types of culture media, modified synthetic oviductal
      fluid (mSOF) and a two-step chemically defined medium (DI/II). To obtain
      parthenogenetic goat embryos, oocytes were matured in vitro in tissue culture
      media-199 supplemented with 10% fetal bovine serum for 22 to 24 hours, and
      activated with 5 MUM, Ca(2+) ionomycin for 4 minutes, followed by 1.9 mM, 6
      dimethylaminopurine treatment for 4 hours. After 2 days of embryo culture in
      different culture media, there were no significant differences in cleavage rates
      (96.6% vs. 95.4% in mSOF vs. DI/II, respectively). However, the DI/II group
      showed improved development competence to blastocysts (64.6% vs. 82.3% in mSOF
      vs. DI/II, respectively) and the total cell number of blastocysts (144.3 +/- 9.2
      vs. 264.4 +/- 15.2 in mSOF vs. DI/II, respectively) at Day 7. After the
      cryopreservation of early-stage blastocysts at Day 6 via the conventional slow
      freezing procedure, the surviving embryos were analyzed. The re-expansion rate
      after freezing and thawing was significantly higher in DI/II (39.66% vs. 67.69%
      in mSOF vs. DI/II, respectively), but there were no statistical differences in
      total cell numbers (142.3 +/- 12.1 vs. 172.1 +/- 11.6 in mSOF vs. DI/II,
      respectively), apoptotic index (4.9 +/- 0.8% vs. 3.8 +/- 0.7 in mSOF vs. DI/II,
      respectively), and the gene expression levels (BAX, GLUT1, MnSOD, and OCT4) among
      the re-expanded blastocysts. Overall, our data reported that the defined in vitro
      culture media for goat embryos were established with high efficiency, which will
      be very useful for goat embryo production. 

PMID- 27020878
TI  - Surgical castration but not immuncastration is associated with reduced
      hypothalamic GnIH and GHRH/GH/IGF-I axis function in male rats.
AB  - Gonadotropin-inhibitory hormone (GnIH) is a potent positive regulator of the
      growth axis. The present study was aimed to comparatively investigate the effects
      of surgical and immunologic castration on hypothalamic GnIH expression and
      endocrine function of the growth axis. Thirty-six prepubertal male rats were
      randomly allocated into three groups (n = 12): control, surgically castrated or
      immunized against 100-MUg D-Lys6-GnRH-tandem peptide conjugated to ovalbumin in
      Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples
      were collected (for hormone and urea nitrogen concentrations) at 2-week
      intervals, and growth performance was evaluated. Compared to intact controls,
      surgical castration reduced (P < 0.05) messenger RNA (mRNA) expressions of
      hypothalamic GnIH and growth hormone-releasing hormone (GHRH), pituitary growth
      hormone (GH), and liver insulin-like growth factor-1 (IGF-1), reduced (P < 0.05)
      serum concentrations of GH and IGF-1 and increased (P < 0.05) serum
      concentrations of urea nitrogen. In contrast, immunocastration did not alter
      messenger RNA expressions of hypothalamic GnIH, GHRH and pituitary GH, and the
      serum concentrations of GH (P > 0.05). Moreover, serum concentrations of IGF-1
      and urea nitrogen in immunocastrates were substantially higher and lower than
      those in surgical castrates, respectively (P < 0.05). Compared to surgical
      castrates, immuncastrates had superior feed conversion efficiency and faster
      daily weight gain (P < 0.05). We concluded that surgical castration but not
      immunocastration is associated with reduced hypothalamic GnIH and GHRH/GH/IGF-I
      axis function in male rats. 

PMID- 27020879
TI  - The effects of kisspeptin agonist canine KP-10 and kisspeptin antagonist p271 on
      plasma LH concentrations during different stages of the estrous cycle and
      anestrus in the bitch.
AB  - Kisspeptin (KP) plays a key role in the regulation of the hypothalamic-pituitary
      gonadal axis via the release of GnRH. As normal KP signaling is essential for
      reproductive function, it could be an interesting new target for therapeutic
      interventions, e.g., nonsurgical contraception in dogs. The aims of the present
      study were to investigate the effect of KP-10 administration on plasma LH
      concentration in different stages of the reproductive cycle and to investigate
      the suitability of p271 as KP antagonist in the bitch. Two groups of six adult
      Beagle bitches were used. In one group, plasma LH concentration was determined
      before (40 and 0 minutes) and 10, 20, 40, and 60 minutes after the intravenous
      administration of 0.5-MUg/kg body weight (BW) canine KP-10. In the other group,
      the bitches received a continuous intravenous infusion with p271 (50 MUg/kg BW/h)
      for 3 hours, and 0.5-MUg/kg BW canine KP-10 was administered intravenously 2
      hours after the start of the p271 infusion. Their plasma LH concentration was
      determined before (-40 and 0 minutes) and 30, 60, 90, 120, 130, 140, 160, and 180
      minutes after the start of the p271 infusion. In both groups, the experiments
      were performed during the follicular phase, the first and second half of the
      luteal phase, and during anestrus. Canine KP-10 induced an increase of plasma LH
      concentration during all estrous cycle stages and anestrus. There was no
      difference in LH response between the two groups. The lowest LH response was seen
      during the follicular phase and the highest response during anestrus. The area
      under the curve (AUC) for LH and LH increment in the follicular phase were lower
      than those in anestrus. The AUC LH and LH increment in the first half of the
      luteal phase were lower than those in the second half of the luteal phase and
      anestrus. The AUC LH and LH increment in the second half of the luteal phase were
      not different from those in anestrus. Continuous administration of the antagonist
      p271 did not alter basal plasma LH concentration and could not prevent or lower
      the LH response to KP-10 in any of the cycle stages and anestrus. It can be
      concluded that the LH response to KP-10 is dependent on estrous cycle stage and
      that peripheral administrated p271 cannot be used as KP antagonist in the dog.
      This provides new insight in reproductive endocrinology of the bitch, which is
      important when KP signaling is considered for therapeutic interventions, such as
      for estrus induction or nonsurgical contraception in the bitch. 

PMID- 27020880
TI  - Expression of 3beta-hydroxysteroid dehydrogenase in ovarian and uterine tissue
      during diestrus and open cervix cystic endometrial hyperplasia-pyometra in the
      bitch.
AB  - The purpose of this study was to compare the expression of 3beta-hydroxystreroid
      dehydrogenase (3beta-HSD) in the uterus and ovary of healthy dogs and those with
      cystic endometrial hyperplasia and/or pyometra complex (CEH-pyometra). Eighteen
      female dogs were included in the study. Eleven bitches with open cervix CEH
      pyometra were included in the CEH-pyometra group and seven diestrus bitches in
      the control group. For immunostaining a rabbit polyclonal, one raised against
      recombinant human type 2 (adrenal/gonadal) 3beta-HSD was used. Progesterone (P4)
      concentrations were not statistically different between the groups. Strongly
      stained large interstitial cell groups in the ovarian medulla were observed
      particularly in CEH-pyometra group although these cells in the control group were
      weakly or moderately stained and existed singly or paired. The expressions of
      3beta-HSD in luminal epithelium (42.40 +/- 22.40% vs. 18.42 +/- 13.15%, P < 0.05)
      and glandular epithelium (32.80 +/- 27.05% vs. 2.94 +/- 7.79%, P < 0.01) of
      endometrium were significantly higher in CEH-pyometra group than those in the
      control group. The expression of 3beta-HSD in CL was higher (29.38 +/- 9.58% vs.
      22.94 +/- 4.97%) in CEH-pyometra group than that of control group although the
      differences were not significant (P > 0.05). Similarly, the significant increase
      in the expression of 3beta-HSD in ovarian interstitial cells (33.86 +/- 29.44 vs.
      1.13 +/- 2.97, P < 0.05) was found in CEH-pyometra group compared to the control
      group. The study revealed that 3beta-HSD expression in the endometrium of canine
      CEH-pyometra was significantly high. 

PMID- 27020881
TI  - Production of feline leukemia inhibitory factor with biological activity in
      Escherichia coli.
AB  - Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and
      embryo development, embryonic stem cell, and induced pluripotent stem cell
      maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the
      human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes
      during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and
      examined its biological activity and effects on oocytes during IVM in the
      domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92%
      with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia
      coli was readily soluble and after purification showed bioactivity in maintaining
      the undifferentiated state of mouse embryonic stem cells and enhancing the
      proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL
      fLIF induced cumulus expansion with or without FSH and EGF (P < 0.05). The rate
      of metaphase II oocytes was also improved with 100-ng/mL fLIF (P < 0.05). We
      therefore confirmed the successful production for the first time of biologically
      active fLIF and revealed its effects on oocytes during IVM in the domestic cat.
      Feline LIF will further improve reproduction and stem cell research in the feline
      family. 

PMID- 27020883
TI  - Interruption of magnesium supply at heading influenced proteome of peripheral
      layers and reduced grain dry weight of two wheat (Triticum aestivum L.)
      genotypes.
AB  - Magnesium (Mg), an indispensable mineral for plant growth, is concentrated in the
      peripheral layers (PLs) of the mature grain of wheat. The supply of Mg was
      interrupted from plant heading to maturity and a proteomic approach was used to
      investigate the PLs at three stages of development. Two genotypes with
      contrasting concentrations of Mg in the grain were studied: Apache (low Mg) and
      MgHL (high Mg). The concentration of Mg was significantly reduced in the roots
      (10-21%), straw (18-50%) and grain (24-10%), respectively. Mg deficiency altered
      enzymes involved in photosynthesis, glycolysis, respiration, amino acid
      synthesis, cell division, protein degradation and folding at early stages,
      especially in MgHL. This latter had smaller grain by reducing grain potential
      size and dry matter accumulation. By contrast in Apache, few proteins were
      affected at early stages and proteins related to stress/defense and
      arginine/proline metabolism were up accumulated resulting in lower number of
      grains per ear (24.9%). This study showed that Mg in PLs plays an important role
      in cell division, ATP generation, carbohydrate and amino acid metabolism, and
      hence may influence grain potential size and assimilates in grain, which
      determines grain weight. These results should help wheat breeders improve Mg
      content and hence grain yield. BIOLOGICAL SIGNIFICANCE: Magnesium (Mg) is an
      abundant cation and is involved in many cell activities. Its role in determining
      wheat productivity remains unclear. This study is the first to investigate how Mg
      deficiency influences the physiological characters of wheat and dry matter in the
      grain in two genotypes with contrasting Mg content. Moreover, Mg is concentrated
      in peripheral layers of grain, which are known to play a critical role in grain
      development. In this study, we investigated proteins in the peripheral layers
      expressed differentially in three development stages to identify the mechanism by
      which Mg influences grain development. This study revealed that the supply of Mg
      influences grain yield and that Mg regulates proteins related to cell metabolism
      and stress defense in grain.

PMID- 27020882
TI  - Ion mobility-enhanced MS(E)-based label-free analysis reveals effects of low-dose
      radiation post contextual fear conditioning training on the mouse hippocampal
      proteome.
AB  - Recent advances in the field of biodosimetry have shown that the response of
      biological systems to ionizing radiation is complex and depends on the type and
      dose of radiation, the tissue(s) exposed, and the time lapsed after exposure. The
      biological effects of low dose radiation on learning and memory are not well
      understood. An ion mobility-enhanced data-independent acquisition (MS(E))
      approach in conjunction with the ISOQuant software tool was utilized for label
      free quantification of hippocampal proteins with the goal of determining protein
      alteration associated with low-dose whole body ionizing radiation (X-rays, 1Gy)
      of 5.5-month-old male C57BL/6J mice post contextual fear conditioning training.
      Global proteome analysis revealed deregulation of 73 proteins (out of 399
      proteins). Deregulated proteins indicated adverse effects of irradiation on
      myelination and perturbation of energy metabolism pathways involving a shift from
      the TCA cycle to glutamate oxidation. Our findings also indicate that proteins
      associated with synaptic activity, including vesicle recycling and
      neurotransmission, were altered in the irradiated mice. The elevated LTP and
      decreased LTD suggest improved synaptic transmission and enhanced efficiency of
      neurotransmitter release which would be consistent with the observed comparable
      contextual fear memory performance of the mice following post-training whole body
      or sham-irradiation. SIGNIFICANCE: This study is significant because the
      biological consequences of low dose radiation on learning and memory are complex
      and not yet well understood. We conducted a IMS-enhanced MS(E)-based label-free
      quantitative proteomic analysis of hippocampal tissue with the goal of
      determining protein alteration associated with low-dose whole body ionizing
      radiation (X-ray, 1Gy) of 5.5-month-old male C57BL/6J mice post contextual fear
      conditioning training. The IMS-enhanced MS(E) approach in conjunction with
      ISOQuant software was robust and accurate with low median CV values of 0.99% for
      the technical replicates of samples from both the sham and irradiated group. The
      biological variance was as low as 1.61% for the sham group and 1.31% for the
      irradiated group. The applied data generation and processing workflow allowed the
      quantitative evaluation of 399 proteins. The current proteomic analysis indicates
      that myelination is sensitive to low dose radiation. The observed protein level
      changes imply modulation of energy metabolism pathways in the radiation exposed
      group, specifically changes in protein abundance levels suggest a shift from TCA
      cycle to glutamate oxidation to satisfy energy demands. Most significantly, our
      study reveals deregulation of proteins involved in processes that govern synaptic
      activity including enhanced synaptic vesicle cycling, and altered long-term
      potentiation (LTP) and depression (LTD). An elevated LTP and decreased LTD
      suggest improved synaptic transmission and enhanced efficiency of
      neurotransmitter release which is consistent with the observed comparable
      contextual fear memory performance of the mice following post-training whole body
      or sham-irradiation. Overall, our results underscore the importance of low dose
      radiation experiments for illuminating the sensitivity of biochemical pathways to
      radiation, and the modulation of potential repair and compensatory response
      mechanisms. This kind of studies and associated findings may ultimately lead to
      the design of strategies for ameliorating hippocampal and CNS injury following
      radiation exposure as part of medical therapies or as a consequence of
      occupational hazards.

PMID- 27020884
TI  - Educational Interventions for Patients With CKD: A Systematic Review.
AB  - BACKGROUND: Preventing progression from earlier stages of chronic kidney disease
      (CKD) to end-stage kidney disease and minimizing the risk for cardiovascular
      events and other complications is central to the management of CKD. Patients'
      active participation in their own care is critical, but may be limited by their
      lack of awareness and understanding of CKD. We aimed to evaluate educational
      interventions for primary and secondary prevention of CKD. STUDY DESIGN:
      Systematic review. Electronic databases were searched to December 2015, with
      study quality assessed using the Cochrane Collaboration risk-of-bias tool.
      SETTING & POPULATION: People with CKD stages 1 to 5 in community and hospital
      settings (studies with only patients with CKD stage 5, kidney transplant
      recipients irrespective of glomerular filtration rate, or patients receiving
      dialysis were excluded). SELECTION CRITERIA FOR STUDIES: Randomized controlled
      trials and nonrandomized studies of educational interventions. INTERVENTIONS:
      Educational strategies in people with CKD. OUTCOMES: Knowledge, self-management,
      quality-of-life, and clinical end points. RESULTS: 26 studies (12 trials, 14
      observational studies) involving 5,403 participants were included. Risk of bias
      was high in most studies. Interventions were multifaceted, including face-to-face
      teaching (26 studies), written information (20 studies), and telephone follow-up
      (13 studies). 20 studies involved 1-on-1 patient/educator interaction and 14
      incorporated group sessions. 9 studies showed improved outcomes for quality of
      life, knowledge, and self-management; 9 had improved clinical end points; and 2
      studies showed improvements in both patient-reported and clinical outcomes.
      Characteristics of effective interventions included teaching sessions that were
      interactive and workshops/practical skills (13/15 studies); integrated negotiated
      goal setting (10/13 studies); involved groups of patients (12/14 studies), their
      families (4/4 studies), and a multidisciplinary team (6/6 studies); and had
      frequent (weekly [4/5 studies] or monthly [7/7 studies]) participant/educator
      encounters. LIMITATIONS: A meta-analysis was not possible due to heterogeneity of
      the interventions and outcomes measured. CONCLUSIONS: Well-designed, interactive,
      frequent, and multifaceted educational interventions that include both individual
      and group participation may improve knowledge, self-management, and patient
      outcomes.

PMID- 27020885
TI  - Supercritical fluid chromatography coupled with in-source atmospheric pressure
      ionization hydrogen/deuterium exchange mass spectrometry for compound speciation.
AB  - An experimental setup for the speciation of compounds by hydrogen/deuterium
      exchange (HDX) with atmospheric pressure ionization while performing
      chromatographic separation is presented. The proposed experimental setup combines
      the high performance supercritical fluid chromatography (SFC) system that can be
      readily used as an inlet for mass spectrometry (MS) and atmospheric pressure
      photo ionization (APPI) or atmospheric pressure chemical ionization (APCI) HDX.
      This combination overcomes the limitation of an approach using conventional
      liquid chromatography (LC) by minimizing the amount of deuterium solvents used
      for separation. In the SFC separation, supercritical CO2 was used as a major
      component of the mobile phase, and methanol was used as a minor co-solvent. By
      using deuterated methanol (CH3OD), AP HDX was achieved during SFC separation. To
      prove the concept, thirty one nitrogen- and/or oxygen-containing standard
      compounds were analyzed by SFC-AP HDX MS. The compounds were successfully
      speciated from the obtained SFC-MS spectra. The exchange ions were observed with
      as low as 1% of CH3OD in the mobile phase, and separation could be performed
      within approximately 20min using approximately 0.24 mL of CH3OD. The results
      showed that SFC separation and APPI/APCI HDX could be successfully performed
      using the suggested method.

PMID- 27020886
TI  - "Heart-cut" bidimensional achiral-chiral liquid chromatography applied to the
      evaluation of stereoselective metabolism, in vivo biological activity and brain
      response to chiral drug candidates targeting the central nervous system.
AB  - A "heart-cut" two-dimensional achiral-chiral liquid chromatography triple
      quadrupole mass spectrometry method (LC-LC-MS/MS) was developed and coupled to in
      vivo cerebral microdialysis to evaluate the brain response to the chiral compound
      (+/-)-7-chloro-5-(3-furanyl)-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1
      dioxide ((+/-)-1), a potent positive allosteric modulator (PAM) of AMPA receptor.
      The method was successfully employed to evaluate also its stereoselective
      metabolism and in vitro biological activity. In particular, the LC achiral method
      developed, employs a pentafluorinated silica based column (Discovery HS-F5) to
      separate dopamine, acetylcholine, serotonin, (+/-)-1 and its two hepatic
      metabolites. In the "heart-cut" two-dimension achiral-chiral configuration, (+/-)
      1 and (+/-)-1-d4 eluted from the achiral column (1st dimension), were transferred
      to a polysaccharide-based chiral column (2nd dimension, Chiralcel OD-RH) by using
      an automatic six-port valve. Single enantiomers of (+/-)-1 were separated and
      detected using electrospray positive ionization mode and quantified in selected
      reaction monitoring mode. The method was validated and showed good performance in
      terms of linearity, accuracy and precision. The new method employed showed
      several possible applications in the evaluation of: (a) brain response to
      neuroactive compounds by measuring variations in the brain extracellular levels
      of selected neurotransmitters and other biomarkers; (b) blood brain barrier
      penetration of drug candidates by measuring the free concentration of the drug in
      selected brain areas; (c) the presence of drug metabolites in the brain
      extracellular fluid that could prove very useful during drug discovery; (d) a
      possible stereoselective metabolization or blood brain barrier stereoselective
      crossing of chiral drugs. Finally, compared to the methods reported in the
      literature, this technique avoids the necessity of euthanizing an animal at each
      time point to measure drug concentration in whole brain tissue and provides
      continuous monitoring of extracellular concentrations of single chiral drug
      enantiomers along with its metabolites in specific brain regions at each selected
      time point for a desired period by using a single animal. 

PMID- 27020887
TI  - Bypassing the Bypass.

PMID- 27020888
TI  - More on the strength of evidence in forensic pathology.

PMID- 27020889
TI  - Hippocampal abnormalities and sudden childhood death.

PMID- 27020890
TI  - Reliability of body size measurements obtained at autopsy: impact on the
      pathologic assessment of the heart.
AB  - Purpose Assessment of body size at autopsy is important for interpreting organ
      weight measurements and in some cases body identification. The reliability of
      post-mortem body size measurements, the causes for perturbations in these
      measurements from their corresponding pre-mortem values, and the impact of such
      perturbations on heart weight interpretation have not been fully explored.
      Methods Autopsy body length and weight measurements and pre-mortem height and
      body weight measurements were compared in 132 autopsies. Clinical records were
      evaluated for peripheral edema and serum albumin levels. Causes of death, body
      cavity fluid collections, and heart weights were obtained from the autopsy
      reports. A subset of patients underwent quantitative post-mortem computed
      tomography assessment of anasarca. Results At autopsy, body weight differed from
      the pre-mortem value by 11 +/- 1 %, compared with -0.2 +/- 0.3 % for body length
      (P < 0.0001). The percent change in body weight at autopsy correlated with the
      presence of peripheral edema (14 +/- 2 % vs. 7 +/- 2 %, P = 0.01), serum albumin
      < 3.0 g/dL (16 +/- 2 % vs. 7 +/- 2 %, P = 0.001), and the degree of anasarca (P =
      0.01). In 4 % of autopsies, heart weights were abnormal based on the pre-mortem
      body weight, but would be classified as normal based on the elevated post-mortem
      body weight. Conclusions At autopsy, body weight is a less reliable parameter
      than body length in correlating with the corresponding pre-mortem measurement.
      Autopsy body weights are elevated in part due to peripheral edema/anasarca.
      Alterations in body weight at autopsy can confound the interpretation of organ
      weight measurements.

PMID- 27020891
TI  - Analysis of RNA modifications by liquid chromatography-tandem mass spectrometry.
AB  - The analysis of RNA modifications is of high importance in order to address a
      wide range of biological questions. Therefore, a highly sensitive and accurate
      method such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) has to
      be available. By using different LC-MS/MS procedures, it is not only possible to
      quantify very low amounts of RNA modifications, but also to detect probably
      unknown modified nucleosides. For these cases the dynamic multiple reaction
      monitoring and the neutral loss scan are the most common techniques. Here, we
      provide the whole workflow for analyzing RNA samples regarding their modification
      content. This includes an equipment list, the preparation of required
      solutions/enzymes and the creation of an internal standard or nucleoside stocks
      for internal or external calibration. Furthermore, we describe the preparation of
      RNA samples for the subsequent LC-MS/MS analysis and the corresponding analysis
      process.

PMID- 27020892
TI  - A fast protocol for purification of translating mRNAs.
AB  - We present a protocol that enables easy extraction of translating mRNAs by
      purification of tagged ribosomes and associated mRNAs. By studying three
      different examples of stress influenced genes, we demonstrate the effectiveness
      and compare our rapid method to an older protocol (Halbeisen et al., 2009).

PMID- 27020893
TI  - Investigating RNA editing factors from trypanosome mitochondria.
AB  - Mitochondrial U-insertion/deletion mRNA editing is carried out by two principal
      multiprotein assemblies, enzymatic RNA editing core (RECC) and RNA editing
      substrate binding (RESC) complexes, and a plethora of auxiliary factors. An
      integral part of mitochondrial gene expression, editing receives inputs from
      primary mRNA and gRNA precursor processing pathways, and generates substrates for
      mRNA polyadenylation and translation. Although nearly all RECC-embedded enzymes
      have been implicated in specific editing reactions, the majority of proteins that
      populate the RESC are also essential for generating edited mRNAs. However, lack
      of recognizable motifs in RESC subunits limits the prowess of bioinformatics in
      guiding biochemical experiments and elucidating their specific biological
      functions. In this chapter, we describe a generic workflow for investigating
      mitochondrial mRNA editing in Trypanosoma brucei and focus on several methods
      that proved instrumental is assigning definitive functions to editing factors
      lacking known signature sequences.

PMID- 27020894
TI  - Endoscopic overtube-guided deployment of a video capsule endoscope.

PMID- 27020895
TI  - Adjustable countertraction during endoscopic submucosal dissection of a large,
      fundus-body, laterally spreading tumor.

PMID- 27020896
TI  - Visualization and removal of intrahepatic bile duct stones through EUS-guided
      hepaticogastrostomy.

PMID- 27020897
TI  - Impacted chicken bone extracted with the aid of Nd:YAG laser.

PMID- 27020898
TI  - Ampullary polyp resection as treatment for severe GI bleeding.

PMID- 27020899
TI  - Per-oral endoscopic myotomy, 1000 cases later: pearls, pitfalls, and practical
      considerations.
AB  - BACKGROUND AND AIMS: Eight years have passed since the introduction of the per
      oral endoscopy myotomy (POEM) procedure. POEM was initially received as an
      investigational procedure, but since the revelation of promising safety and
      efficacy data, it is becoming the preferred treatment for achalasia. With the
      recent completion of our 1000th POEM procedure, we share our experience and
      knowledge through the discussion of clinical pearls, pitfalls, and practical
      considerations. METHODS: The various aspects of the procedure and conditions that
      warrant special attention are discussed from our perspective, with a focus on
      areas in which there is currently limited evidence. RESULTS: The key points on
      patient position, submucosal tunneling, myotomy, closure, intraprocedural
      bleeding, and advanced sigmoid achalasia are presented. CONCLUSIONS: The
      dissemination of this information serves as a foundation for new POEM operators
      and as a catalyst for more-experienced operators to further refine and advance
      their POEM skills and stimulate international discourse and collaboration.

PMID- 27020900
TI  - Open abdomen with negative pressure device vs primary abdominal closure for the
      management of surgical abdominal sepsis: a retrospective review.
AB  - BACKGROUND: Open abdomen with temporary abdominal closure remains a controversial
      management strategy for surgical abdominal sepsis compared with primary abdominal
      closure (PAC) and on-demand laparotomy. The primary objective was to compare
      mortality between PAC and open abdomen with vacuum assisted closure (VAC).
      METHODS: Retrospective review of a tertiary center intensive care unit database
      (2006 to 2010) including suspected/diagnosed severe abdominal sepsis/septic shock
      requiring source control laparotomy. Groups were categorized according to closure
      method at index source control laparotomy. APACHE-IV was used as a measure of
      disease severity. RESULTS: Of 211 patients, 75 PAC and 136 VAC cases were
      included. Controlling for disease severity, adjusted odds ratio of mortality for
      VAC was .41 95% confidence interval (.21, .81; P = .01) compared with PAC. PAC
      and VAC APACHE-1V predicted mortality rate were both 45%. VAC mortality was lower
      than PAC (22.8% vs 38.6%; P = .012). CONCLUSIONS: Open abdomen with VAC is
      associated with significantly improved survival compared with PAC in abdominal
      sepsis requiring laparotomy.

PMID- 27020901
TI  - Remote just-in-time telementored trauma ultrasound: a double-factorial randomized
      controlled trial examining fluid detection and remote knobology control through
      an ultrasound graphic user interface display.
AB  - BACKGROUND: Remote-telementored ultrasound involves novice examiners being
      remotely guided by experts using informatic-technologies. However, requiring a
      novice to perform ultrasound is a cognitively demanding task exacerbated by
      unfamiliarity with ultrasound-machine controls. We incorporated a randomized
      evaluation of using remote control of the ultrasound functionality (knobology)
      within a study in which the images generated by distant naive examiners were
      viewed on an ultrasound graphic user interface (GUI) display viewed on laptop
      computers by mentors in different cities. METHODS: Fire-fighters in Edmonton
      (101) were remotely mentored from Calgary (n = 65), Nanaimo (n = 19), and Memphis
      (n = 17) to examine an ultrasound phantom randomized to contain free fluid or
      not. Remote mentors (2 surgeons, 1 internist, and 1 ED physician) were randomly
      assigned to use GUI knobology control during mentoring (GUIK+/GUIK-). RESULTS:
      Remote-telementored ultrasound was feasible in all cases. Overall accuracy for
      fluid detection was 97% (confidence interval = 91 to 99%) with 3 false negatives
      (FNs). Positive/negative likelihood ratios were infinity/0.0625. One FN occurred
      with the GUIK+ and 2 without (GUIK-). There were no statistical test performance
      differences in either group (GUIK+ and GUIK-). CONCLUSIONS: Ultrasound-naive 1st
      responders can be remotely mentored with high accuracy, although providing basic
      remote control of the knobology did not affect outcomes.

PMID- 27020902
TI  - Routine intraoperative leak testing for sleeve gastrectomy: is the leak test full
      of hot air?
AB  - BACKGROUND: Staple line leak after sleeve gastrectomy (SG) is a rare but dreaded
      complication with a reported incidence of 0% to 8%. Many surgeons routinely test
      the staple line with an intraoperative leak test (IOLT), but there is little
      evidence to validate this practice. In fact, there is a theoretical concern that
      the leak test may weaken the staple line and increase the risk of a postop leak.
      METHODS: Retrospective review of all SGs performed over a 7-year period was
      conducted. Cases were grouped by whether an IOLT was performed, and compared for
      the incidence of postop staple line leaks. The ability of the IOLT for
      identifying a staple line defect and for predicting a postoperative leak was
      analyzed. RESULTS: Five hundred forty-two SGs were performed between 2007 and
      2014. Thirteen patients (2.4%) developed a postop staple line leak. The majority
      of patients (n = 494, 91%) received an IOLT, including all 13 patients (100%) who
      developed a subsequent clinical leak. There were no (0%) positive IOLTs and no
      additional interventions were performed based on the IOLT. The IOLT sensitivity
      and positive predictive value were both 0%. There was a trend, although not
      significant, to increase leak rates when a routine IOLT was performed vs no
      routine IOLT (2.6% vs 0%, P = .6). CONCLUSIONS: The performance of routine IOLT
      after SG provided no actionable information, and was negative in all patients who
      developed a postoperative leak. The routine use of an IOLT did not reduce the
      incidence of postop leak, and in fact was associated with a higher leak rate
      after SG.

PMID- 27020903
TI  - The sympathy of two pendulum clocks: beyond Huygens' observations.
AB  - This paper introduces a modern version of the classical Huygens' experiment on
      synchronization of pendulum clocks. The version presented here consists of two
      monumental pendulum clocks--ad hoc designed and fabricated--which are coupled
      through a wooden structure. It is demonstrated that the coupled clocks exhibit
      'sympathetic' motion, i.e. the pendula of the clocks oscillate in consonance and
      in the same direction. Interestingly, when the clocks are synchronized, the
      common oscillation frequency decreases, i.e. the clocks become slow and
      inaccurate. In order to rigorously explain these findings, a mathematical model
      for the coupled clocks is obtained by using well-established physical and
      mechanical laws and likewise, a theoretical analysis is conducted. Ultimately,
      the sympathy of two monumental pendulum clocks, interacting via a flexible
      coupling structure, is experimentally, numerically, and analytically
      demonstrated.

PMID- 27020905
TI  - Advanced technology in interventional cardiology: A roadmap for the future of
      precision coronary interventions.
AB  - Several specific new technologies [high-resolution CT coronary imaging with
      fractional flow reserve (CTCA-FFR), virtual reality (VR), vascular robotic
      systems (VRS), and three-dimensional printing] are poised to improve the
      treatment of patients with cardiovascular disease and at the same time the safety
      of the physicians who care for them. This article focuses on the potential
      clinical impact each of these modalities will have, as well as speculating on
      synergies that use of them together may achieve.

PMID- 27020904
TI  - Stem cell therapy for heart failure: Ensuring regenerative proficiency.
AB  - Patient-derived stem cells enable promising regenerative strategies, but display
      heterogenous cardiac reparative proficiency, leading to unpredictable therapeutic
      outcomes impeding practice adoption. Means to establish and certify the
      regenerative potency of emerging biotherapies are thus warranted. In this era of
      clinomics, deconvolution of variant cytoreparative performance in clinical trials
      offers an unprecedented opportunity to map pathways that segregate regenerative
      from non-regenerative states informing the evolution of cardio-regenerative
      quality systems. A maiden example of this approach is cardiopoiesis-mediated
      lineage specification developed to ensure regenerative performance. Successfully
      tested in pre-clinical and early clinical studies, the safety and efficacy of the
      cardiopoietic stem cell phenotype is undergoing validation in pivotal trials for
      chronic ischemic cardiomyopathy offering the prospect of a next-generation
      regenerative solution for heart failure.

PMID- 27020906
TI  - Early findings in outbreak of haemolytic uraemic syndrome among young children
      caused by Shiga toxin-producing Escherichia coli, Romania, January to February
      2016.
AB  - As at 29 February 2016, 15 cases of haemolytic uraemic syndrome with onset
      between 25 January and 22 February were reported among children between five and
      38 months in Romania, and three of them died. Cases were mostly from southern
      Romania. Six cases tested positive for Escherichia coli O26 by serology. Fruits,
      vegetables, meat and dairy products were among the possible common food
      exposures. Investigations are ongoing in Romania to control the outbreak.

PMID- 27020907
TI  - Prevalence, Severity, and Prognostic Effect of Hepatopulmonary Syndrome in Liver
      Transplant Candidates.
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) is commonly encountered in the setting
      of end-stage liver disease (ESLD). Past studies have reported conflicting results
      in terms of demonstrating an association between HPS and mortality. The aim of
      this study was to determine the prevalence of HPS in patients with ESLD referred
      for assessment of transplantation suitability. In addition, we investigated
      survival rates in the setting of HPS, with and without liver transplantation.
      MATERIAL AND METHODS: The medical records of 524 consecutive patients with ESLD
      evaluated for potential liver transplantation were retrospectively reviewed. HPS
      was defined by a reduced partial pressure of oxygen or an elevated alveolar
      arterial oxygen gradient and the presence of intrapulmonary vascular dilatation
      on contrast-enhanced echocardiography. RESULTS: In total, 57 subjects (12%)
      fulfilled the diagnostic criteria of HPS; 88% of these had mild to moderate HPS.
      For patients with HPS, the overall survival rates at 1 and 3 years were 95% and
      92%, respectively. Liver transplants were received by 245 patients (53%), 26 of
      whom had HPS. For transplant recipients with HPS, the overall survival rates at 1
      and 3 years were 96% and 91%, respectively, compared to 85% and 80% in subjects
      without HPS. Post-transplantation survival in patients with and without HPS did
      not differ significantly (HR=0.489, 95% CI: 0.153-1.564; p=0.228). CONCLUSIONS:
      This study demonstrated a high prevalence of IPVD and HPS among patients who were
      potential candidates for liver transplantation. HPS was mild to moderate in the
      majority of those affected and had no significant effect on overall survival.

PMID- 27020908
TI  - Concurrent and prospective associations of intolerance of uncertainty with
      symptoms of prolonged grief, posttraumatic stress, and depression after
      bereavement.
AB  - This study examined associations of Prospective IU and Inhibitory IU with symptom
      levels of Prolonged Grief Disorder (PGD), Posttraumatic Stress-Disorder (PTSD),
      and depression in a sample of bereaved individuals. Specifically, 265 bereaved
      individuals completed measures of IU, PGD, PTSD, and depression in the first year
      after the death of a loved one; 134 participants again completed symptom-measures
      six months later. Cross-sectional analyses showed that Inhibitory IU (but not
      Prospective IU) was positively associated with symptom-levels of PTSD and
      depression (but not PGD), even when controlling for neuroticism, worry, and
      rumination. Prospective analyses showed that Prospective IU (but not Inhibitory
      IU) at baseline, predicted PGD severity six months later (but not PTSD or
      depression at follow-up) while controlling for baseline symptom-levels. The
      findings support the notion that IU is a vulnerability factor for different
      emotional problems, including those developing after the death of a loved one.
      Clinical implications of these findings are discussed.

PMID- 27020909
TI  - Anatomical relationship between mental foramen, mandibular teeth and risk of
      nerve injury with endodontic treatment.
AB  - OBJECTIVES: The objective of the present study was to evaluate the anatomical
      relationship between mental foramen (MF), including the incidence of the anterior
      loop of the inferior alveolar nerve (AL), and roots of mandibular teeth in
      relation to risk of nerve injury with endodontic treatment. MATERIALS AND
      METHODS: Cone-beam computed tomography (CBCT) images, which included teeth either
      side of the MF, were randomly selected. The anonymised CBCT images were
      reconstructed and examined in coronal, axial and sagittal planes, using three
      dimensional viewing software, to determine the relationship and distance between
      MF and adjacent mandibular teeth. The actual distance between the root apex and
      MF was calculated mathematically using Pythagoras' theorem. If present, the
      incidence of an AL in the axial plane was also recorded. RESULTS: The root apex
      of the mandibular second premolar (70 %), followed by the first premolar (18 %)
      and then the first molar (12 %), was the closest to the MF. Ninety-six percent of
      root apices evaluated were >3 mm from the MF. An AL was present in 88 % of the
      cases. CONCLUSIONS: With regards to endodontic treatment, the risk of nerve
      injury in the vicinity of the MF would appear to be low. However, the high
      incidence of the AL highlights the need for clinicians to be aware and careful of
      this important anatomical feature. CLINICAL RELEVANCE: The risk of injury to the
      MN with endodontic treatment would appear to be low, but given the high
      incidence, it is important to be aware and be careful of the AL.

PMID- 27020910
TI  - Antibacterial properties of copper iodide-doped glass ionomer-based materials and
      effect of copper iodide nanoparticles on collagen degradation.
AB  - OBJECTIVES: This study investigated the antibacterial properties and micro
      hardness of polyacrylic acid (PAA)-coated copper iodide (CuI) nanoparticles
      incorporated into glass ionomer-based materials, and the effect of PAA-CuI on
      collagen degradation. MATERIALS AND METHODS: PAA-CuI nanoparticles were
      incorporated into glass ionomer (GI), Ionofil Molar AC, and resin-modified glass
      ionomer (RMGI), Vitrebond, at 0.263 wt%. The antibacterial properties against
      Streptococcus mutans (n = 6/group) and surface micro-hardness (n = 5/group) were
      evaluated. Twenty dentin beams were completely demineralized in 10 wt% phosphoric
      acid and equally divided in two groups (n = 10/group) for incubation in simulated
      body fluid (SBF) or SBF containing 1 mg/ml PAA-CuI. The amount of dry mass loss
      and hydroxyproline (HYP) released were quantified. Kruskal-Wallis, Student's t
      test, two-way ANOVA, and Mann-Whitney were used to analyze the antibacterial,
      micro-hardness, dry mass, and HYP release data, respectively (p < 0.05). RESULTS:
      Addition of PAA-CuI nanoparticles into the glass ionomer matrix yielded
      significant reduction (99.999 %) in the concentration of bacteria relative to the
      control groups. While micro-hardness values of PAA-CuI-doped GI were no different
      from its control, PAA-CuI-doped RMGI demonstrated significantly higher values
      than its control. A significant decrease in dry mass weight was shown only for
      the control beams (10.53 %, p = 0.04). Significantly less HYP was released from
      beams incubated in PAA-CuI relative to the control beams (p < 0.001).
      CONCLUSIONS: PAA-CuI nanoparticles are an effective additive to glass ionomer
      based materials as they greatly enhance their antibacterial properties and reduce
      collagen degradation without an adverse effect on their mechanical properties.
      CLINICAL RELEVANCE: The use of copper-doped glass ionomer-based materials under
      composite restorations may contribute to an increased longevity of adhesive
      restorations, because of their enhanced antibacterial properties and reduced
      collagen degradation.

PMID- 27020911
TI  - Comparison of anesthetic efficacy of 2 and 4 % articaine in inferior alveolar
      nerve block for tooth extraction-a double-blinded randomized clinical trial.
AB  - OBJECTIVES: The purpose of this clinical prospective, randomized, double-blind
      trial was to compare the anesthetic efficacy of 2 % articaine and 4 % articaine
      in inferior alveolar nerve block anesthesia for extraction of mandibular teeth.
      MATERIALS AND METHODS: In 95 patients, 105 lower molar and premolar teeth were
      extracted after intraoral inferior alveolar nerve block. In 53 cases, 2 %
      articaine (group I) and, in 52 cases, 4 % articaine (group II) was administered.
      The primary objective was to analyze the differences of anesthetic effects
      between the two groups (complete/sufficient vs. insufficient/none). Furthermore,
      differences in pulpal anesthesia (onset and depth, examined with pulp vitality
      tester (min)), as well as in length of soft tissue anesthesia (min), were
      evaluated. Additionally, the need of a second injection, pain while injecting
      (numeric rating scale (NRS)), pain during treatment (NRS), pain after treatment
      (NRS), and other possible complications (excessive pain, bleeding events,
      prolonged deafness) were analyzed. RESULTS: Anesthesia was sufficient for dental
      extractions in both groups without significant differences (p = 0.201). The onset
      of anesthesia did not differ significantly (p = 0.297). A significantly shorter
      duration of soft tissue anesthesia was seen in group I (2.9 vs. 4 h; p < 0.001).
      There was no significant difference in the need for a second injection (p =
      0.359), in injection pain (p = 0.386), as well as in pain during (p = 0.287) or
      after treatment (p = 0.121). In both groups, no complications were seen.
      CONCLUSIONS: The local anesthetic effect of the 4 % articaine solution is not
      significantly better when compared to 2 % articaine. CLINICAL RELEVANCE: For
      mandibular tooth extraction, articaine 2 % may be used as alternative as well.

PMID- 27020912
TI  - In situ effect of a CPP-ACP chewing gum on enamel erosion associated or not with
      abrasion.
AB  - OBJECTIVES: The purpose of this study is to analyze the in situ effect of a
      casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) chewing
      gum on human enamel erosion lesion associated or not with abrasion. MATERIAL AND
      METHODS: A three-way crossover study of 7 days was conducted involving 10
      volunteers subjected to the same protocol: (G1) CPP-ACP sugar-free chewing gum,
      (G2) regular sugar-free chewing gum without CPP-ACP, and (G3) saliva-no chewing
      gum. An abrasion test was included in each phase. A 3D non-contact profilometry
      measurement of lesion depth and surface roughness was obtained of sound and
      eroded surfaces. A salivary calcium concentration was determined for all
      volunteers. ANOVA followed by Tukey's test were used with a p < 0.05. RESULTS:
      The enamel depth and the enamel surface roughness of the CPP-ACP gum group were
      significantly lower than the others (ANOVA, p < 0.05). No significant differences
      were observed between the treatments when associated with abrasion (p > 0.05). A
      positive and significant correlation was seen between the lesion depth and enamel
      surface roughness for GI (r = 0.87, p = 0.00) and GIII (r = 0.79, p = 0.00)
      groups. The estimated total calcium presented in the saliva after the chewed CPP
      ACP gum showed no statistical significance between the mean absorbance values at
      the different time collections (p > 0.05). CONCLUSIONS: It is demonstrated that
      the incorporation of the CPP-ACP into a sugar-free gum significantly increased
      the remineralization/protection of eroded enamel surface. CLINICAL RELEVANCE: The
      CPP-ACP added to gum may be a suitable alternative vehicle, to deliver calcium
      ions to saliva and therefore protecting enamel.

PMID- 27020913
TI  - The innervation of the soft palate muscles involved in cleft palate: a review of
      the literature.
AB  - OBJECTIVE: Surgical techniques to obtain adequate soft palate repair in cleft
      palate patients elaborate on the muscle repair; however, there is little
      available information regarding the innervation of muscles. Improved insights
      into the innervation of the musculature will likely allow improvements in the
      repair of the cleft palate and subsequently decrease the incidence of
      velopharyngeal insufficiency. We performed a literature review focusing on recent
      advances in the understanding of soft palate muscle innervation. MATERIAL AND
      METHODS: The Medline and Embase databases were searched for anatomical studies
      concerning the innervation of the soft palate. RESULTS: Our literature review
      highlights the lack of accurate information about the innervation of the levator
      veli palatini and palatopharyngeus muscles. It is probable that the lesser
      palatine nerve and the pharyngeal plexus dually innervate the levator veli
      palatini and palatopharyngeus muscles. Nerves of the superior-extravelar part of
      the levator veli palatini and palatopharyngeus muscles enter the muscle form the
      lateral side. Subsequently, the lesser palatine nerve enters from the lateral
      side of the inferior-velar part of the levator veli palatini muscle. This
      knowledge could aid surgeons during reconstruction of the cleft musculature. The
      innervation of the tensor veli palatini muscle by a small branch of the
      mandibular nerve was confirmed in all studies. CONCLUSION: Both the levator veli
      palatini and palatopharyngeus muscles receive motor fibres from the accessory
      nerve (through the vagus nerve and the glossopharyngeal nerve) and also the
      lesser palatine nerve. A small branch of the mandibular nerve innervates the
      tensor veli palatini muscle. CLINICAL RELEVANCE: Knowledge about these nerves
      could aid the cleft surgeon to perform a more careful dissection of the lateral
      side of the musculature.

PMID- 27020915
TI  - Photoluminescence through in-gap states in phenylacetylene functionalized silicon
      nanocrystals.
AB  - Optoelectronic properties of Si nanocrystals (SiNCs) were studied by combining
      scanning tunneling spectroscopy (STS) and optical measurements. The
      photoluminescence (PL) of phenylacetylene functionalized SiNCs red shifts
      relative to hexyl- and phenyl-capped counterparts, whereas the absorption spectra
      and the band gaps extracted from STS are similar for all surface groups. However,
      an in-gap state near the conduction band edge was detected by STS only for the
      phenylacetylene terminated SiNCs, which can account for the PL shift via
      relaxation across this state. 

PMID- 27020914
TI  - Accuracy of commercial kits and published primer pairs for the detection of
      periodontopathogens.
AB  - OBJECTIVES: Despite the input of microbiome research, a group of 20 bacteria
      continues to be the focus of periodontal diagnostics and therapy. The aim of this
      study was to compare three commercial kits and laboratory-developed primer pairs
      for effectiveness in detecting such periodontopathogens. MATERIALS AND METHODS:
      Fourteen bacterial mock communities, consisting of 16 randomly assembled
      bacterial strains, were used as reference standard for testing kits and primers.
      Extracted DNA from mock communities was analyzed by PCR in-house with specific
      primers and forwarded for analysis to the manufacturer's laboratory of each of
      the following kits: ParoCheck(r)Kit 20, micro-IDent(r)plus11, and Carpegen(r)
      Perio Diagnostik. RESULTS: The kits accurately detected Fusobacterium nucleatum,
      Prevotella intermedia/Prevotella nigrescens, Parvimonas micra, Aggregatibacter
      actinomycetemcomitans, Campylobacter rectus/showae, Streptococcus mitis,
      Streptococcus mutans, and Veillonella parvula. The in-house primers for
      F.nucleatum were highly specific to subtypes of the respective periopathogen.
      Other primers repeatedly detected oral pathogens not present in the mock
      communities, indicating reduced specificity. CONCLUSIONS: The commercial kits
      used in this study are reliable tools to support periodontal diagnostics. Whereas
      the detection profile of the kits is fixed at a general specificity level, the
      design of primers can be adjusted to differentiate between highly specific
      strains. In-house primers are more error-prone. Bacterial mock communities can be
      established as a reference standard for any similar testing. CLINICAL RELEVANCE:
      The tested kits render good results with selected bacterial species. Primers
      appear to be less useful for routine clinical diagnostics and of limited
      applicability in research. Basic information about the periodontopathogens
      identified in this study supports clinical decision-making.

PMID- 27020916
TI  - Plant and soil fungal but not soil bacterial communities are linked in long-term
      fertilized grassland.
AB  - Inorganic fertilization and mowing alter soil factors with subsequent effects
      direct and indirect - on above- and below-ground communities. We explored direct
      and indirect effects of long-term fertilization (N, P, NPK, Liming) and twice
      yearly mowing on the plant, bacterial and fungal communities and soil factors. We
      analyzed co-variation using 16S and 18S rRNA genes surveys, and plant frequency
      and edaphic factors across treatments. The plant and fungal communities were
      distinct in the NPK and L treatments, while the bacterial communities and soil
      factors were distinct in the N and L treatments. Plant community diversity and
      evenness had low diversity in the NPK and high diversity in the liming treatment,
      while the diversity and evenness of the bacterial and fungal communities did not
      differ across treatments, except of higher diversity and evenness in the liming
      treatment for the bacteria. We found significant co-structures between
      communities based on plant and fungal comparisons but not between plant and
      bacterial nor bacterial and fungal comparisons. Our results suggested that the
      plant and fungal communities are more tightly linked than either community with
      the bacterial community in fertilized soils. We found co-varying plant, bacterial
      and fungal taxa in different treatments that may indicate ecological
      interactions. 

PMID- 27020917
TI  - Chemical poisonings, new and old.

PMID- 27020918
TI  - Bigdata Oriented Multimedia Mobile Health Applications.
AB  - In this paper, two mHealth applications are introduced, which can be employed as
      the terminals of bigdata based health service to collect information for
      electronic medical records (EMRs). The first one is a hybrid system for improving
      the user experience in the hyperbaric oxygen chamber by 3D stereoscopic virtual
      reality glasses and immersive perception. Several HMDs have been tested and
      compared. The second application is a voice interactive serious game as a likely
      solution for providing assistive rehabilitation tool for therapists. The recorder
      of the voice of patients could be analysed to evaluate the long-time
      rehabilitation results and further to predict the rehabilitation process. 

PMID- 27020919
TI  - Assessing protein-DNA interactions: Pros and cons of classic and emerging
      techniques.

PMID- 27020920
TI  - Functional spermatid-like cells derived from the ground-state embryonic stem
      cells in vitro.

PMID- 27020921
TI  - Effects of Minimally Invasive Esophagectomy and Open Esophagectomy on Circulating
      Tumor Cell Level in Elderly Patients with Esophageal Cancer.
AB  - OBJECTIVE: To investigate the effects of minimally invasive esophagectomy (MIE)
      and open esophagectomy (OE) on circulating tumor cell (CTC) level of elderly
      patients with esophageal cancer (EC). METHODS: A total of 78 elderly EC patients
      who aged over 64 years were divided into the MIE group (n = 40) and the OE group
      (n = 38). CTC enrichment was performed through CD326 (EpCAM) immunomagnetic beads
      positive sorting, and then labeled by CK-PE and CD45. The quantity of CTCs was
      measured by multiparameter flow cytometry. Double antibody sandwich enzyme-linked
      immuno sorbent assay ELISA (DAS-ELISA) was used for detecting the levels of IL-6,
      IL-10, and IFN-gamma. RESULTS: Among the 78 elderly EC patients, CTC level after
      the surgery was higher than that during the surgery, and CTC level during surgery
      was higher than that before the surgery (both P < 0.05). Postoperative CTC level
      in the MIE group was lower than that in the OE group, and the variation of CTC
      level from pre-operation to intra-operation in the MIE group was also lower than
      that in the OE group (both P < 0.05). Furthermore, there was significant
      difference in the incidences of intra-operative and postoperative complications
      between the MIE group and the OE group (17 cases vs. 31 cases, P < 0.05), and the
      CTC levels of the patients with complications in either group were significantly
      higher than the patients without complications (both P < 0.05). IL-6 and IL-10
      levels significantly increased, while IFN-gamma level decreased in both groups
      during the surgery and 3 days after the surgery compared to those before the
      surgery; 2 weeks after the surgery, IL-6 and IL-10 levels in the MIE group
      recovered to the pre-operative levels (all P < 0.05). However, in the OE group,
      IL-6 and IL-10 levels 2 weeks after the surgery were still significantly higher
      than those before the surgery (all P < 0.05); IFN-gamma levels in both groups
      recovered to the pre-operative levels, with higher level in the MIE group than
      that in the OE group (P < 0.05). CONCLUSION: MIE helped to reduce the survival
      rate of tumor cells in peripheral blood at the early period of postoperation, and
      dynamic monitoring CTC level could be used to evaluate the prognosis of EC
      patients.

PMID- 27020922
TI  - Use of anticancer agents in gynecological oncology during pregnancy: a systematic
      review of maternal pharmacokinetics and transplacental transfer.
AB  - INTRODUCTION: Cancer affects one in a thousand pregnant women and gynecological
      cancers are one of the most frequent malignancies. Chemotherapy remains the
      cornerstone treatment for gynecological cancer. Although all chemotherapeutic
      agents can cross the placental barrier, the extent of placental transfer varies
      considerably. Furthermore, the significant physiological variations observed in
      pregnant women may have an impact on pharmacokinetic parameters. Given the
      complexity of predicting placental transfer, in vivo and ex vivo studies are
      essential in this context. In view of the paucity of data on chemotherapy during
      pregnancy, the objective of the present study was to summarize all the available
      data on the transplacental transfer of anticancer drugs used to treat
      gynecological cancers. AREAS COVERED: In order to evaluate the in vivo and ex
      vivo transplacental transfer of the anticancer drugs most frequently used in
      gynecological malignancies, we carried out a comprehensive review of the
      literature published from 1967 to 2015. Lastly, we summarized recent clinical
      guidelines on the treatment of gynecological cancers in pregnant patients. EXPERT
      OPINION: The preclinical and scarce clinical data must now be extrapolated to
      define the maternofetal toxicity/efficacy profile and thus guide the physicians
      to choose anticancer drugs more efficiently in this complex situation.

PMID- 27020923
TI  - Nanocrystalline SrS:Ce3+ system for the generation of white light-emitting
      diodes.
AB  - Nanocrystalline SrS phosphors doped with Ce3+ ions at different concentrations
      (0.5, 1, 1.5 and 2 mol%) are synthesized via the solid-state diffusion method
      (SSDM), which is suitable for the large-scale production of phosphors in
      industrial applications. The as-prepared samples are characterized using an X-ray
      diffraction (XRD) technique, field emission scanning electron microscopy (FESEM),
      high-resolution transmission electron microscopy (HRTEM) and energy-dispersive X
      ray (EDX) analysis. The optical properties of these phosphors are analyzed using
      reflectance spectra, photoluminescence spectra and afterglow decay curves. The
      cubic structure of the SrS phosphor is confirmed by XRD analysis and the
      crystallite size calculated by Scherer's formula using XRD data shows the
      nanocrystalline nature of the phosphors. No phase change is observed with
      increasing concentrations of Ce3+ ions. The surface morphology of the prepared
      phosphors is determined by FESEM, which shows a sphere-like structure and good
      connectivity of the grains. The authenticity of the formation of nanocrystalline
      phosphors is examined by HRTEM analysis. Elemental compositional information for
      the prepared phosphors is gathered by EDX analysis. Photoluminescence studies
      reveal that the emission spectra of the prepared phosphor shows broad band
      emission centered at 458 and 550 nm due to the transition of electrons from the
      5d -> 4f energy levels. The afterglow decay characteristics of different as
      synthesized SrS:Ce3+ nanophosphors are conceptually described. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27020924
TI  - Direct and Sensitive Detection of CWA Simulants by Active Capillary Plasma
      Ionization Coupled to a Handheld Ion Trap Mass Spectrometer.
AB  - An active capillary plasma ionization (ACI) source was coupled to a handheld mass
      spectrometer (Mini 10.5; Aston Labs, West Lafayette, IN, USA) and applied to the
      direct gas-phase detection and quantification of chemical warfare agent (CWA)
      related chemicals. Complementing the discontinuous atmospheric pressure interface
      (DAPI) of the Mini 10.5 mass spectrometer with an additional membrane pump, a
      quasi-continuous sample introduction through the ACI source was achieved. Nerve
      agent simulants (three dialkyl alkylphosphonates, a dialkyl phosporamidate, and
      the pesticide dichlorvos) were detected at low gas-phase concentrations with
      limits of detection ranging from 1.0 MUg/m(3) to 6.3 MUg/m(3). Our results
      demonstrate a sensitivity enhancement for portable MS-instrumentation by using an
      ACI source, enabling direct, quantitative measurements of volatile organic
      compounds. Due to its high sensitivity, selectivity, low power consumption (<80
      W) and weight (<13 kg), this instrumentation has the potential for direct on-site
      CWA detection as required by military or civil protection. Graphical Abstract ?.

PMID- 27020925
TI  - Acquiring Structural Information on Virus Particles with Charge Detection Mass
      Spectrometry.
AB  - Charge detection mass spectrometry (CDMS) is a single-molecule technique
      particularly well-suited to measuring the mass and charge distributions of
      heterogeneous, MDa-sized ions. In this work, CDMS has been used to analyze the
      assembly products of two coat protein variants of bacteriophage P22. The assembly
      products show broad mass distributions extending from 5 to 15 MDa for A285Y and 5
      to 25 MDa for A285T coat protein variants. Because the charge of large ions
      generated by electrospray ionization depends on their size, the charge can be
      used to distinguish hollow shells from more compact structures. A285T was found
      to form T = 4 and T = 7 procapsids, and A285Y makes a small number of T = 3 and T
      = 4 procapsids. Owing to the decreased stability of the A285Y and A285T
      particles, chemical cross-linking was required to stabilize them for electrospray
      CDMS.Graphical Abstract.

PMID- 27020926
TI  - Selective Covalent Chemistry via Gas-Phase Ion/ion Reactions: An Exploration of
      the Energy Surfaces Associated with N-Hydroxysuccinimide Ester Reagents and
      Primary Amines and Guanidine Groups.
AB  - Selective covalent bond forming reactions (referred to as covalent reactions) can
      occur in gas-phase ion/ion reactions and take place via the formation of a long
      lived chemical complex. The gas-phase ion/ion reactivity between sulfo-N
      hydroxysuccinimide (sulfo-NHS) ester reagent anions and peptide cations
      containing a primary amine or guanidine group has been examined via DFT
      calculations and complex dissociation rate measurements. The results reveal
      insights regarding the roles of the barriers of competing processes within the
      complex. When the covalent reaction is exothermic, two prototypical cases,
      determined by the nature of the energy surface, are apparent. The product
      partitioning between covalent reaction and simple proton transfer upon
      dissociation of the long-lived complex is sensitive to activation conditions when
      the transition state barrier for covalent reaction is relatively high (case 1)
      but is insensitive to activation conditions when the transition state barrier is
      relatively low (case 2). Covalent reaction efficiencies are very high in case 2
      scenarios, such as when the reactive site is a guanidine and the anion attachment
      site is a guanidinium ion. Covalent reaction efficiencies are variable, and
      generally low, in case 1 scenarios, such as when an amine is the reactive site
      and an ammonium ion is the site of anion attachment. A relatively long slow
      heating step prior to the complex dissociation step, however, can dramatically
      increase covalent reaction yield in case 1 scenarios. Graphical Abstract ?.

PMID- 27020927
TI  - Determination of elemental impurities in pharmaceutical products and related
      matrices by ICP-based methods: a review.
AB  - Interest in the determination of elemental impurities in pharmaceuticals has
      increased in recent years because of changes in regulatory requirements and the
      need for changing or updating the current limit tests recommended in
      pharmacopeias. Inductively coupled plasma (ICP) optical emission spectrometry and
      ICP mass spectrometry are suitable alternatives to perform multielemental
      analysis for this purpose. The main advantages and limitations of these
      techniques are described, covering the applications reported in the literature in
      the last 10 years mainly for active pharmaceutical ingredients, raw materials,
      and pharmaceutical dosage forms. Strategies used for sample preparation,
      including dissolution in aqueous or organic solvents, extraction, wet digestion
      and combustion methods are described, as well as direct solid analysis and ICP
      based systems applied for speciation analysis. Interferences observed during the
      analysis of pharmaceutical products using ICP-based methods are discussed.
      Methods currently recommended by pharmacopeias for elemental impurities are also
      covered, showing that the use of ICP-based methods could be considered as a trend
      in the determination of these impurities in pharmaceuticals. However, the
      development of a general method that is accurate for all elemental impurities and
      the establishment of an official method are still challenges. In this regard, the
      main drawbacks and suitable alternatives are discussed. 

PMID- 27020928
TI  - In vitro RNA release from a human rhinovirus monitored by means of a molecular
      beacon and chip electrophoresis.
AB  - Liquid-phase electrophoresis either in the classical capillary format or
      miniaturized (chip CE) is a valuable tool for quality control of virus
      preparations and for targeting questions related to conformational changes of
      viruses during infection. We present an in vitro assay to follow the release of
      the RNA genome from a human rhinovirus (common cold virus) by using a molecular
      beacon (MB) and chip CE. The MB, a probe that becomes fluorescent upon
      hybridization to a complementary sequence, was designed to bind close to the 3'
      end of the viral genome. Addition of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman
      2-carboxylic acid), a well-known additive for reduction of bleaching and blinking
      of fluorophores in fluorescence microscopy, to the background electrolyte
      increased the sensitivity of our chip CE set-up. Hence, a fast, sensitive and
      straightforward method for the detection of viral RNA is introduced.
      Additionally, challenges of our assay will be discussed. In particular, we found
      that (i) desalting of virus preparations prior to analysis increased the recorded
      signal and (ii) the MB-RNA complex signal decreased with the time of virus
      storage at -70  degrees C. This suggests that 3'-proximal sequences of the viral
      RNA, if not the whole genome, underwent degradation during storage and/or
      freezing and thawing. In summary, we demonstrate, for two independent virus
      batches, that chip electrophoresis can be used to monitor MB hybridization to RNA
      released upon incubation of the native virus at 56  degrees C. Graphical Abstract
      Schematic of the study strategy: RNA released from HRV-A2 is detected by chip
      electrophoresis through the increase in fluorescence after genom complexation to
      a cognate molecular beacon. 

PMID- 27020929
TI  - Development and validation of an LC-ESI-MS/MS method for the simultaneous
      quantification of naproxen and sumatriptan in human plasma: application to a
      pharmacokinetic study.
AB  - A sensitive and fast liquid chromatography-electrospray ionization tandem mass
      spectrometry (LC-ESI-MS/MS) method was developed and validated for the
      simultaneous quantification of naproxen and sumatriptan in human plasma. A simple
      liquid-liquid extraction procedure, with a mixture of ethyl acetate, methyl tert
      butyl ether, and dichloromethane (4:3:3, v/v), was used for the cleanup of
      plasma. Naratriptan and aceclofenac were employed as internal standards. The
      analyses were carried out using an ACE C18 column (50 * 4.6 mm i.d.; particle
      size 5 MUm) and a mobile phase consisting of 2 mM aqueous ammonium acetate with
      0.025 % formic acid and methanol (38:62, v/v). A triple-quadrupole mass
      spectrometer equipped with an electrospray source in the positive mode was set up
      in the selective reaction monitoring mode to detect the ion transitions m/z
      231.67 -> m/z 185.07, m/z 296.70 -> m/z 157.30, m/z 354.80 -> m/z 215.00, and m/z
      336.80 -> m/z 97.94 for naproxen, sumatriptan, aceclofenac, and naratriptan,
      respectively. The method was validated and proved to be linear, accurate,
      precise, and selective over the ranges of 2.5-130 MUg mL(-1) for naproxen and 1
      50 ng mL(-1) for sumatriptan. The validated method was successfully applied to a
      pharmacokinetic study with simultaneous administration of naproxen sodium and
      sumatriptan succinate tablet formulations in healthy volunteers. 

PMID- 27020930
TI  - Detection of nitroaromatic explosives by new D-pi-A sensing fluorophores on the
      basis of the pyrimidine scaffold.
AB  - A series of D-pi-A- type dyes based on pyrimidines, bearing various thiophene
      linkers, have been studied as sensing fluorophores. Fluorescence studies have
      demonstrated that the emission of all derivatives is sensitive to the presence of
      nitroaromatic explosives, such as 2,4,6-trinitrophenol (PA), 2,4,6
      trinitrotoluene (TNT), and 2,4-dinitrotoluene (DNT), in their acetonitrile
      solutions. The detection limits of fluorophores to PA, TNT, and DNT proved to be
      in the range from 5.83 * 10(-6) to 2.38 * 10(-7) mol/L, 1.70 * 10(-4) to 8.40 *
      10(-6) mol/L, and 8.39 * 10(-5) to 6.87 * 10(-6) mol/L, respectively. The
      theoretical investigation into the quenching mechanism in the presence of
      fluorophore has been performed. All compounds have shown a good efficiency as
      sensor materials when tested as elements of the original device "Nitroscan" for
      detecting nitro-containing explosives in vapor phase (Plant "Promautomatika",
      Ekaterinburg, Russia). Graphical Abstract ?. 

PMID- 27020931
TI  - Disaster Risk Education of Final Year High School Students Requires a Partnership
      with Families and Charity Organizations: An International Cross-sectional Survey.
AB  - Introduction The aim of disaster reduction education (DRE) is to achieve
      behavioral change. Over the past two decades, many efforts have been directed
      towards this goal, but educational activities have been developed based on
      unverified assumptions. Further, the literature has not identified any
      significant change towards disaster preparedness at the individual level. In
      addition, previous research suggests that change is dependent on multiple
      independent predictors. It is difficult to determine what specific actions DRE
      might result in; therefore, the preamble of such an action, which is to have
      discussions about it, has been chosen as the surrogate outcome measure for DRE
      success. This study describes the relationship of the perceived entity
      responsible for disaster education, disaster education per se, sex, and country
      specific characteristics, with students discussing disasters with friends and
      family as a measure of proactive behavioral change in disaster preparedness.
      METHODS: A total of 3,829 final year high school students participated in an
      international, multi-center prospective, cross-sectional study using a validated
      questionnaire. Nine countries with different levels of disaster exposure risk and
      economic development were surveyed. Regression analyses examined the relationship
      between the likelihood of discussing disasters with friends and family (dependent
      variable) and a series of independent variables. RESULTS: There was no
      statistically significant relationship between a single entity responsible for
      disaster education and discussions about potential hazards and risks with friends
      and/or family. While several independent predictors showed a significant main
      effect, DRE through school lessons in interaction with Family & Charity
      Organizations had the highest predictive value. CONCLUSIONS: Disaster reduction
      education might require different delivery channels and methods and should engage
      with the entities with which the teenagers are more likely to collaborate.
      Codreanu TA , Celenza A , Ngo H . Disaster risk education of final year high
      school students requires a partnership with families and charity organizations:
      an international cross-sectional survey. Prehosp Disaster Med. 2016;31(3):242
      254.

PMID- 27020932
TI  - Multidimensional Sexual Perfectionism and Female Sexual Function: A Longitudinal
      Investigation.
AB  - Research on multidimensional sexual perfectionism differentiates four forms: self
      oriented, partner-oriented, partner-prescribed, and socially prescribed. Self
      oriented sexual perfectionism reflects perfectionistic standards people apply to
      themselves as sexual partners; partner-oriented sexual perfectionism reflects
      perfectionistic standards people apply to their sexual partner; partner
      prescribed sexual perfectionism reflects people's beliefs that their sexual
      partner imposes perfectionistic standards on them; and socially prescribed sexual
      perfectionism reflects people's beliefs that society imposes such standards on
      them. Previous studies found partner-prescribed and socially prescribed sexual
      perfectionism to be maladaptive forms of sexual perfectionism associated with a
      negative sexual self-concept and problematic sexual behaviors, but only examined
      cross-sectional relationships. The present article presents the first
      longitudinal study examining whether multidimensional sexual perfectionism
      predicts changes in sexual self-concept and sexual function over time. A total of
      366 women aged 17-69 years completed measures of multidimensional sexual
      perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and
      sexual function (cross-sectional data). Three to six months later, 164 of the
      women completed the same measures again (longitudinal data). Across analyses,
      partner-prescribed sexual perfectionism emerged as the most maladaptive form of
      sexual perfectionism. In the cross-sectional data, partner-prescribed sexual
      perfectionism showed positive relationships with sexual anxiety, sexual problem
      self-blame, and intercourse pain, and negative relationships with sexual esteem,
      desire, arousal, lubrication, and orgasmic function. In the longitudinal data,
      partner-prescribed sexual perfectionism predicted increases in sexual anxiety and
      decreases in sexual esteem, arousal, and lubrication over time. The findings
      suggest that partner-prescribed sexual perfectionism contributes to women's
      negative sexual self-concept and female sexual dysfunction.

PMID- 27020933
TI  - Addiction Training: Striving to Fill an Unmet Need.

PMID- 27020934
TI  - Mentorship: A Return to Basics.

PMID- 27020935
TI  - Statement Regarding the National Resident Matching Program Child and Adolescent
      Psychiatry Match: A Call to Uphold the Gentlepersons' Agreement.

PMID- 27020936
TI  - Professional Integrity and the Role of Medical Students in Professional Self
      Regulation.

PMID- 27020937
TI  - Hunting for hydrogen: random structure searching and prediction of NMR parameters
      of hydrous wadsleyite.
AB  - The structural chemistry of materials containing low levels of nonstoichiometric
      hydrogen is difficult to determine, and producing structural models is
      challenging where hydrogen has no fixed crystallographic site. Here we
      demonstrate a computational approach employing ab initio random structure
      searching (AIRSS) to generate a series of candidate structures for hydrous
      wadsleyite (beta-Mg2SiO4 with 1.6 wt% H2O), a high-pressure mineral proposed as a
      repository for water in the Earth's transition zone. Aligning with previous
      experimental work, we solely consider models with Mg3 (over Mg1, Mg2 or Si)
      vacancies. We adapt the AIRSS method by starting with anhydrous wadsleyite,
      removing a single Mg(2+) and randomly placing two H(+) in a unit cell model,
      generating 819 candidate structures. 103 geometries were then subjected to more
      accurate optimisation under periodic DFT. Using this approach, we find the most
      favourable hydration mechanism involves protonation of two O1 sites around the
      Mg3 vacancy. The formation of silanol groups on O3 or O4 sites (with loss of
      stable O1-H hydroxyls) coincides with an increase in total enthalpy. Importantly,
      the approach we employ allows observables such as NMR parameters to be computed
      for each structure. We consider hydrous wadsleyite (~1.6 wt%) to be dominated by
      protonated O1 sites, with O3/O4-H silanol groups present as defects, a model that
      maps well onto experimental studies at higher levels of hydration (J. M. Griffin
      et al., Chem. Sci., 2013, 4, 1523). The AIRSS approach adopted herein provides
      the crucial link between atomic-scale structure and experimental studies.

PMID- 27020938
TI  - Mood Disorders in Middle-Aged and Older Veterans With Multimorbidity.
AB  - OBJECTIVE: This study identified the prevalence of and relationship between mood
      disorders and multimorbidity in middle-aged and older veterans. METHOD: Cross
      sectional data were obtained from veterans who received primary care services at
      VA Pittsburgh Healthcare System from January 2007 to December 2011 ( n = 34,786).
      RESULTS: Most veterans had three or more organ systems with chronic disease
      (95.3%), of which 4.1% had a depressive disorder, 2.5% had an anxiety disorder,
      and 0.7% had co-occurring depression and anxiety. The odds of having a mood
      disorder increased with each additional organ system with chronic disease, with
      odds being the greatest in those with 10 to 13 organ systems with chronic
      disease. Younger age, female gender, non-married marital status, and having a
      service connected disability were also significant predictors of having a mood
      disorder. DISCUSSION: These findings suggest a need to integrate mental health
      assessment and treatment in chronic health care management for veterans.

PMID- 27020939
TI  - Prevalent mutator genotype identified in fungal pathogen Candida glabrata
      promotes multi-drug resistance.
AB  - The fungal pathogen Candida glabrata has emerged as a major health threat since
      it readily acquires resistance to multiple drug classes, including triazoles
      and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of
      resistance to multiple drug classes have not been described in this organism.
      Here we demonstrate that a mutator phenotype caused by a mismatch repair defect
      is prevalent in C. glabrata clinical isolates. Strains carrying alterations in
      mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal
      treatment in vitro and in mouse models of colonization, and are recovered at a
      high rate (55% of all C. glabrata recovered) from patients. This genetic
      mechanism promotes the acquisition of resistance to multiple antifungals, at
      least partially explaining the elevated rates of triazole and multi-drug
      resistance associated with C. glabrata. We anticipate that identifying MSH2
      defects in infecting strains may influence the management of patients on
      antifungal drug therapy. 

PMID- 27020940
TI  - A protocol to assess the impact of adding nursing support workers to ward
      staffing.
AB  - AIM: To assess the impact of adding nursing support workers to ward staffing.
      BACKGROUND: Nurses' capacity to provide safe care is compromised by increased
      workloads and nursing shortages. Use of unregulated workers is an alternative to
      increasing the number of regulated nurses. The impact of adding nursing support
      workers on patient, nurse and system outcomes has not been systematically
      evaluated. DESIGN: A mixed longitudinal and cross-sectional design using
      administrative data sets and prospective data from a sample of wards. METHODS:
      Payroll data will identify wards on which unregulated staff work. To assess the
      impact on nursing-sensitive outcomes, retrospective analysis of morbidity and
      mortality data of all patients admitted to Western Australia hospitals for over
      24 hours across 4 years will be undertaken. For the cross-sectional study, a
      sample of 20 pairs of matched wards will be selected: 10 with unregulated workers
      added and 10 where they have not. From this sample the impact on patients will be
      assessed using the Patient Evaluation of Emotional Care during Hospitalisation
      survey. The impact on nurses will be assessed by a nurse survey used extensively
      which includes variables such as job satisfaction and intention to leave. The
      impact on system outcomes will be explored using work sampling of staff
      activities and the Practice Environment Scale. Interviews will determine nurses'
      experience of working with nursing support workers. DISCUSSION: The study aims to
      provide evidence about the impact of adding nursing support workers to ward
      staffing for patients, staff and the work environment.

PMID- 27020941
TI  - Levels of anti-fructose-modified HSA antibodies correlate with disease status in
      diabetic subjects.
AB  - OBJECTIVE: This study aimed to assess the changes induced in HSA upon fructose
      modification and to use the modified protein as an antigen for studying the
      presence of antibodies in diabetic patients. Further, magnitude of oxidative
      stress was also assessed. METHODS: HSA was modified with fructose, changes
      induced were studied by DSC measurements and near-UV CD. The binding
      characteristics of antibodies in the sera of diabetes patients to native and
      modified-HSA was assessed by ELISA and band shift assay. The oxidative stress in
      these patients was studied by carbonyl content estimation, FRAP assay and TBARS
      determination RESULTS: DSC revealed that fructose modified-HSA was more
      thermostable than its native form. Changes in tertiary structure of fructose
      modified HSA were seen in near-UV CD. Patient studies showed that fructose
      modified HSA acts as a potent immunogen compared to its native form and the
      levels of antibodies against fructose-modified HSA served as a parameter for
      tracking the glycemic control and oxidative stress parameters (carbonyl content,
      FRAP value and MDA level) in diabetic patients. CONCLUSIONS: Fructose
      modification of HSA causes perturbations in its structure and function, thereby,
      making the protein antigenic besides decreasing its antioxidant capacity. This
      study suggests that fructose-modified-HSA is an important contributor in diabetic
      pathophysiology.

PMID- 27020942
TI  - C. butyricum lipoteichoic acid inhibits the inflammatory response and apoptosis
      in HT-29 cells induced by S. aureus lipoteichoic acid.
AB  - Lipoteichoic acid (LTA) is one of microbe-associated molecular pattern (MAMP)
      molecules of gram-positive bacteria. In this study, we demonstrated that
      Clostridium butyricum LTA (bLTA) significantly inhibited the inflammatory
      response and apoptosis induced by Staphylococcus aureus LTA (aLTA) in HT-29
      cells. aLTA stimulated the inflammatory responses by activating a strong signal
      transduction cascade through NF-kappaB and ERK, but bLTA did not activate the
      signaling pathway. bLTA pretreatment inhibited the activation of the NF-kappaB
      and ERK signaling pathway induced by aLTA. The expression and release of
      cytokines such as IL-8 and TNF-alpha were also suppressed by bLTA pretreatment.
      aLTA treatment induced apoptosis in HT-29 cells, but bLTA did not affect the
      viability of the cells. Further study indicated that bLTA inhibited apoptosis in
      HT-29 cells induced by aLTA. These results suggest that bLTA may act as an aLTA
      antagonist and that an antagonistic bLTA may be a useful agent for suppressing
      the pro-inflammatory activities of gram-positive pathogenic bacteria. 

PMID- 27020944
TI  - Fabrication of nonwoven fabrics consisting of gelatin nanofibers cross-linked by
      glutaraldehyde or N-acetyl-d-glucosamine by aqueous method.
AB  - Since gelatin (Gel) undergoes a sol-gel transition, a novel dry-spinning
      procedure for Gel was used. Here, nonwoven fabrics of Gel were electrospun by
      applying the principles of dry spinning. The diameter of the fibers and the
      viscosity and flow rate of the solution were directly dependent on the
      concentration of Gel. Nonwoven fabrics spun with a 25% (w/w) Gel concentration
      only exhibited a nanoscale fiber diameter. In order to improve the properties of
      the nonwoven fabrics, they were cross-linked with glutaraldehyde (GTA) vapor
      after spinning or by the addition of N-acetyl-d-glucosamine (GlcNAc) to the Gel
      solution prior to spinning followed by heating these fibers. The developed
      nonwoven fibers were characterized using SEM, rheometry, FTIR, TGA, and
      mechanical tensile testing. The nonwoven fabrics cross-linked by the GTA vapor
      exhibited improved mechanical properties compared to those without cross-linking
      or with GlcNAc cross-linking. The swelling and water uptake ability resulted in
      no morphological changes in the fibers with GTA cross-linking. The TGA thermogram
      confirmed no phase change in the composite structure. Further, in vitro
      cytocompatibility studies using human mesenchymal stem cells showed the
      compatible nature of the developed nonwoven fibers. Our studies showed that these
      nonwoven fibers could be useful in medical care.

PMID- 27020943
TI  - Designing tragacanth gum based sterile hydrogel by radiation method for use in
      drug delivery and wound dressing applications.
AB  - Present article discusses synthesis and characterization of the sterile and pure
      hydrogel wound dressings which were prepared through radiation method by using
      polyvinyl alcohol (PVA), tragacanth gum (TG) and sodium alginate (SA). The
      polymer films were characterized by SEM, Cryo-SEM, FTIR, solid state C(13) NMR
      and XRD, TGA, and DSC. Some important biological properties such as O2
      permeability, water vapor transmission rate, microbial permeability, haemolysis,
      thrombogenic behavior, antioxidant activity, bio-adhesion and mechanical
      properties were also studied. The hydrogel film showed thrombogenicity (82.43+/
      1.54%), haemolysis (0.83+/-0.09%), oxygen permeability (6.433+/-0.058mg/L) and
      water vapor permeability (197.39+/-25.34g/m(2)/day). Hydrogel films were found
      biocompatible and impermeable to microbes. The release of antibiotic drug
      moxifloxacin occurred through non-Fickian mechanism and release profile was best
      fitted in Hixson-Crowell model for drug release. Overall, these results indicate
      the suitability of these hydrogels in wound dressing applications. 

PMID- 27020945
TI  - Habitat residency and movement patterns of Centropomus parallelus juveniles in a
      subtropical estuarine complex.
AB  - Sixty Centropomus parallelus juveniles were collected in March 2013 in two
      locations (Tromomo and Guaraguacu) inside the Paranagua estuarine complex,
      southern Brazil. The habitat residency and movement patterns of the individuals
      were inferred from Sr:Ca ratios and age recorded in the otoliths. Data suggest
      that the species spawns preferentially in brackish areas mainly from October to
      January, and that growth rate during the early juvenile stage could be influenced
      by environmental salinity. Furthermore, the data also show that C. parallelus can
      occupy diverse salinity habitats and migrate among marine, brackish and
      freshwater areas within the Paranagua estuarine complex, showing a high
      environmental plasticity and adaptation. 

PMID- 27020946
TI  - Regioselective self-acylating cyclodextrins in organic solvent.
AB  - Amphiphilic cyclodextrins have been synthesized with self-acylating reaction
      using vinyl esters in dimethylformamide. In the present study no base, catalyst,
      or enzyme was used, and the structural analyses using thin layer chromatography,
      nuclear magnetic resonance spectroscopy and mass spectrometry show that the
      cyclodextrin is substituted preferentially by one acyl moiety at the C2 position
      of the glucose unit, suggesting that cyclodextrin functions as a regioselective
      catalytic carbohydrate in organic solvent. In the self-acylation, the most acidic
      OH group at the 2-position and the inclusion complexing ability of cyclodextrin
      were considered to be significant. The substrate preference was also observed in
      favor of the long-chain acyl group, which could be attributed to the inclusion
      ability of cyclodextrin cavity. Furthermore, using the model amphiphilic building
      block, 2-O-mono-lauryl beta-cyclodextrin, the self-organized supramolecular
      architecture with nano-vesicular morphology in water was investigated by
      fluorescence spectroscopy, dynamic light scattering and transmission electron
      microscopy. The cavity-type nano-assembled vesicle and the novel synthetic
      methods for the preparation of mono-acylated cyclodextrin should be of great
      interest with regard to drug/gene delivery systems, functional surfactants, and
      carbohydrate derivatization methods. 

PMID- 27020947
TI  - Reconstructing communities in cluster trials?
AB  - BACKGROUND: There is growing interest in the ethics of cluster trials, but no
      literature on the uncertainties in defining communities in relation to the
      scientific notion of the cluster in collaborative biomedical research. METHODS:
      The views of participants in a community-based cluster randomised trial (CRT) in
      Mumbai, India, were solicited regarding their understanding and views on
      community. We conducted two focus group discussions with local residents and 20
      semi-structured interviews with different respondent groups. On average, ten
      participants took part in each focus group, most of them women aged 18-55. We
      conducted semi-structured interviews with ten residents (nine women and one man)
      lasting approximately an hour each and seven individuals (five men and two women)
      identified by residents as local leaders or decision-makers. In addition, we
      interviewed two Municipal Corporators (locally elected government officials
      involved in urban planning and development) and one representative of a political
      party located in a slum community. RESULTS: Residents' sense of community largely
      matched the scientific notion of the cluster, defined by the investigators as a
      geographic area, but their perceived needs were not entirely met by the trial.
      CONCLUSION: We examined whether the possibility of a conceptual mismatch between
      'clusters' and 'communities' is likely to have methodological implications for a
      study or to lead to potential social disharmony because of the research
      interventions, arguing that it is important to take social factors into account
      as well as statistical efficiency when choosing the size and type of clusters and
      designing a trial. One method of informing such a design would be to use existing
      forums for community engagement to explore individuals' primary sense of
      community or social group and, where possible, to fit clusters around them. TRIAL
      REGISTRATION: ISRCTN Register: ISRCTN56183183 Clinical Trials Registry of India:
      CTRI/2012/09/003004 .

PMID- 27020948
TI  - The Detection of Infectious Prions: In Vitro Conversion Assays Change the
      (Folding) Landscape.
AB  - This commentary highlights the article by Gray et al describing a novel
      diagnostic protocol for rapidly testing transmissible spongiform
      encephalopathies.

PMID- 27020949
TI  - Relative benefits of newer adjuvant chemotherapy regimens in luminal breast
      cancer subtypes.

PMID- 27020950
TI  - Low-frequency brain stimulation to the left dorsolateral prefrontal cortex
      increases the negative impact of social exclusion among those high in personal
      distress.
AB  - The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the
      cognitive control of emotion and has therefore, unsurprisingly, been implicated
      in the regulation of physical pain perception. This brain region may also
      influence the experience of social pain, which has been shown to activate similar
      neural networks as seen in response to physical pain. Here, we applied sham or
      active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS)
      to the left DLPFC, previously shown to exert bilateral effects in pain
      perception, in healthy participants. Following stimulation, participants played
      the "Cyberball Task"; an online ball-tossing game in which the subject
      participant is included or excluded. Compared to sham, rTMS did not modulate
      behavioural response to social exclusion. However, within the active rTMS group
      only, greater trait personal distress was related to enhanced negative outcomes
      to social exclusion. These results add further support to the notion that the
      effect of brain stimulation is not homogenous across individuals, and indicates
      the need to consider baseline individual differences when assessing response to
      brain stimulation. This seems particularly relevant in social neuroscience
      investigations, where trait factors may have a meaningful effect.

PMID- 27020951
TI  - Characterization and anti-biofilm activity of extracellular polymeric substances
      produced by the marine biofilm-forming bacterium Pseudoalteromonas ulvae strain
      TC14.
AB  - This study investigated soluble (Sol-EPS), loosely bound (LB-EPS), and tightly
      bound extracellular polymeric substances (TB-EPS) harvested from biofilm and
      planktonic cultures of the marine bacterium Pseudoalteromonas ulvae TC14. The aim
      of the characterization (colorimetric methods, FTIR, GC-MS, NMR, HPGPC, and AFM
      analyses) was to identify new anti-biofilm compounds; activity was assessed using
      the BioFilm Ring Test(r). A step-wise separation of EPS was designed, based on
      differences in water-solubility and acidity. An acidic fraction was isolated from
      TB-EPS, which strongly inhibited biofilm formation by marine bacterial strains in
      a concentration-dependent manner. The main constituents of this fraction were
      characterized as two glucan-like polysaccharides. An active poly(glutamyl
      glutamate) fraction was also recovered from TB-EPS. The distribution of these key
      EPS components in Sol-EPS, LB-EPS, and TB-EPS was distinct and differed
      quantitatively in biofilm vs planktonic cultures. The anti-biofilm potential of
      the fractions emphasizes the putative antifouling role of EPS in the environment.

PMID- 27020952
TI  - High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior
      Pituitary Basophilic Cells.
AB  - Emerging evidence shows that elevated cholesterol levels are detrimental to
      health. However, it is unclear whether there is an association between
      cholesterol and the pituitary. We investigated the effects of a high-cholesterol
      diet on pituitary hormones using in vivo animal studies and an epidemiological
      study. In the animal experiments, rats were fed a high-cholesterol or control
      diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid
      stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH)
      and follicle-stimulating hormone (FSH) produced by the basophilic cells of the
      anterior pituitary were elevated in a time-dependent manner. Among these
      hormones, TSH was the first to undergo a significant change, whereas
      adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic
      cells, was not changed significantly. As the duration of cholesterol feeding
      increased, cholesterol deposition increased gradually in the pituitary.
      Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs,
      showed an obvious increase in cell area, as well as a potential increase in their
      proportion of total pituitary cells. Expression of the beta-subunit of TSH, FSH
      and LH, which controls hormone specificity and activity, exhibited a
      corresponding increase. In the epidemiological study, we found a similar
      elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with
      hypercholesterolaemia. Significant positive correlations existed between serum
      total cholesterol and TSH, FSH or LH, even after adjusting for confounding
      factors. Taken together, the results of the present study suggest that the high
      cholesterol diet affected the levels of hormones derived from anterior pituitary
      basophilic cells. This phenomenon might contribute to the pituitary functional
      disturbances described in hypercholesterolaemia. 

PMID- 27020953
TI  - Crystal-induced arthritis after arthroplasty: 7 cases.
AB  - OBJECTIVES: To describe the occurrence in prosthetic joints of crystal-induced
      arthritis (CIA) defined as the deposition within the synovial membrane and/or
      joint cavity of calcium pyrophosphate dehydrate (CPPD) (chondrocalcinosis),
      sodium urate (gout), or hydroxyapatite. METHODS: We retrospectively reviewed the
      7 cases of prosthetic-joint CIA seen between 1993 and 2013 at a medical-surgical
      center specialized in the management of osteoarticular infections. RESULTS: The 4
      females and 3 males ranged in age from 67 to 79 years. Acute CIA occurred at the
      knee in 6 patients (5 with total knee arthroplasty and 1 with unicompartmental
      knee arthroplasty) and at the hip in 1 patient (with total hip arthroplasty).
      Time from arthroplasty to CIA varied from 7 days to 9 years. An abrupt onset was
      a consistent feature, with pain, complete loss of function, and local evidence of
      inflammation. A single patient had a fever and 6 patients had laboratory evidence
      of systemic inflammation. Joint aspiration showed hemarthrosis in 3 patients and
      inflammatory joint fluid with 20,000 to 79,000neutrophils/mm(3) in 6 patients.
      Joint fluid cultures were negative in 6 patients. CPPD crystals were evidenced in
      5 patients, including 1 who also had hydroxyapatite crystals detected by electron
      microscopy after alizarin red staining. Monosodium urate crystals were found in 1
      patient. The remaining patient had both CPPD crystals and positive cultures for
      Campylobacter fetus. In 5 patients, treatment with colchicine or a nonsteroidal
      antiinflammatory drug ensured prompt control of the symptoms and systemic
      inflammation. The patient with total hip arthroplasty underwent joint aspiration
      for hemarthrosis. In 1 patient, an intraarticular injection of triamcinolone
      hexacetonide improved the symptoms and systemic inflammation. The patient with
      Campylobacter fetus infection was treated with antibiotics, excision of the
      abscess, and synovectomy. CONCLUSION: CIA may occur after arthroplasty, within
      synovial membrane remains or neosynovium developed around the prosthetic joint.
      CIA is a manifestation of a metabolic disease that persists and can reactivate
      after surgery. Routine testing for crystals is rarely performed in patients with
      sterile arthritis of a prosthetic joint, and crystals are difficult to detect in
      joints with hemarthrosis; consequently, the frequency of prosthetic-joint CIA may
      be underestimated. Although rare, CIA should be considered routinely when
      symptoms suggesting septic arthritis develop in a prosthetic joint, in order to
      avoid unnecessary prolonged antibiotic therapy and, in some cases, surgery. The
      treatment is usually simple.

PMID- 27020955
TI  - Evolution of virulence in Photorhabdus spp., entomopathogenic nematode symbionts.
AB  - Photorhabdus is a genus of Gram-negative bacteria belonging to the
      Enterobacteriaceae family. In addition to forming a mutualistic relationship with
      the Heterorhabditidae family of nematodes, these bacteria are the causal agent of
      insect mortality during nematode infection, and are commonly used as biocontrol
      agents against pest insects in managed ecosystems. There are three described
      species of Photorhabdus; Photorhabdus luminescens and Photorhabdus temperata,
      which are strictly entomopathogens, and Photorhabdus asymbiotica, which has been
      isolated from wound infections in humans. While there has been extensive research
      on its virulence mechanisms, the evolution of virulence in Photorhabdus has not
      previously been investigated within a phylogenetic context. To investigate how
      virulence has evolved in this genus, we first reconstructed the phylogenetic
      relationships among 18 strains representing each of the main taxonomic lineages
      in the genus. Bacterial cells were injected into Galleria mellonella and Tenebrio
      molitor larvae, and the LT50 was calculated for each strain. These values were
      mapped onto the phylogeny using ancestral character reconstruction methods. With
      few exceptions, we found that the general trend of Photorhabdus evolution is one
      of increasing virulence. We also explored the relationship between virulence and
      Photorhabdus cell types and growth rates. Although we found no correlation
      between cell type and virulence, there was a strong correlation between virulence
      and growth rates in T. molitor. A better understanding of the origin and
      maintenance of virulence in this bacterium will aid in unraveling the mechanisms
      of the Heterorhabditis-Photorhabdus complex, resulting in the selection of more
      effective nematode-bacterium complexes for biocontrol. 

PMID- 27020956
TI  - Adaptive plant physiology in extreme environments.

PMID- 27020957
TI  - xGDBvm: A Web GUI-Driven Workflow for Annotating Eukaryotic Genomes in the Cloud.
AB  - Genome-wide annotation of gene structure requires the integration of numerous
      computational steps. Currently, annotation is arguably best accomplished through
      collaboration of bioinformatics and domain experts, with broad community
      involvement. However, such a collaborative approach is not scalable at today's
      pace of sequence generation. To address this problem, we developed the xGDBvm
      software, which uses an intuitive graphical user interface to access a number of
      common genome analysis and gene structure tools, preconfigured in a self
      contained virtual machine image. Once their virtual machine instance is deployed
      through iPlant's Atmosphere cloud services, users access the xGDBvm workflow via
      a unified Web interface to manage inputs, set program parameters, configure links
      to high-performance computing (HPC) resources, view and manage output, apply
      analysis and editing tools, or access contextual help. The xGDBvm workflow will
      mask the genome, compute spliced alignments from transcript and/or protein inputs
      (locally or on a remote HPC cluster), predict gene structures and gene structure
      quality, and display output in a public or private genome browser complete with
      accessory tools. Problematic gene predictions are flagged and can be reannotated
      using the integrated yrGATE annotation tool. xGDBvm can also be configured to
      append or replace existing data or load precomputed data. Multiple genomes can be
      annotated and displayed, and outputs can be archived for sharing or backup.
      xGDBvm can be adapted to a variety of use cases including de novo genome
      annotation, reannotation, comparison of different annotations, and training or
      teaching.

PMID- 27020958
TI  - UV-B Perception and Acclimation in Chlamydomonas reinhardtii.
AB  - Plants perceive UV-B, an intrinsic component of sunlight, via a signaling pathway
      that is mediated by the photoreceptor UV RESISTANCE LOCUS8 (UVR8) and induces UV
      B acclimation. To test whether similar UV-B perception mechanisms exist in the
      evolutionarily distant green alga Chlamydomonas reinhardtii, we identified
      Chlamydomonas orthologs of UVR8 and the key signaling factor CONSTITUTIVELY
      PHOTOMORPHOGENIC1 (COP1). Cr-UVR8 shares sequence and structural similarity to
      Arabidopsis thaliana UVR8, has conserved tryptophan residues for UV-B
      photoreception, monomerizes upon UV-B exposure, and interacts with Cr-COP1 in a
      UV-B-dependent manner. Moreover, Cr-UVR8 can interact with At-COP1 and complement
      the Arabidopsis uvr8 mutant, demonstrating that it is a functional UV-B
      photoreceptor. Chlamydomonas shows apparent UV-B acclimation in colony survival
      and photosynthetic efficiency assays. UV-B exposure, at low levels that induce
      acclimation, led to broad changes in the Chlamydomonas transcriptome, including
      in genes related to photosynthesis. Impaired UV-B-induced activation in the Cr
      COP1 mutant hit1 indicates that UVR8-COP1 signaling induces transcriptome changes
      in response to UV-B. Also, hit1 mutants are impaired in UV-B acclimation.
      Chlamydomonas UV-B acclimation preserved the photosystem II core proteins D1 and
      D2 under UV-B stress, which mitigated UV-B-induced photoinhibition. These
      findings highlight the early evolution of UVR8 photoreceptor signaling in the
      green lineage to induce UV-B acclimation and protection.

PMID- 27020960
TI  - Competing antiferromagnetic orders in the double perovskite Mn2MnReO6 (Mn3ReO6).
AB  - The new double perovskite Mn2MnReO6 has been synthesised at high pressure. Mn(2+)
      and Re(6+) spins order antiferromagnetically through two successive transitions
      that are coupled by magnetoelastic effects, as order of the Mn spins at 109 K
      leads to lattice distortions that reduce frustration prompting Re order at 99 K. 

PMID- 27020959
TI  - The Evolutionarily Conserved Protein PHOTOSYNTHESIS AFFECTED MUTANT71 Is Required
      for Efficient Manganese Uptake at the Thylakoid Membrane in Arabidopsis.
AB  - In plants, algae, and cyanobacteria, photosystem II (PSII) catalyzes the light
      driven oxidation of water. The oxygen-evolving complex of PSII is a Mn4CaO5
      cluster embedded in a well-defined protein environment in the thylakoid membrane.
      However, transport of manganese and calcium into the thylakoid lumen remains
      poorly understood. Here, we show that Arabidopsis thaliana PHOTOSYNTHESIS
      AFFECTED MUTANT71 (PAM71) is an integral thylakoid membrane protein involved in
      Mn(2+) and Ca(2+) homeostasis in chloroplasts. This protein is required for
      normal operation of the oxygen-evolving complex (as evidenced by oxygen evolution
      rates) and for manganese incorporation. Manganese binding to PSII was severely
      reduced in pam71 thylakoids, particularly in PSII supercomplexes. In cation
      partitioning assays with intact chloroplasts, Mn(2+) and Ca(2+) ions were
      differently sequestered in pam71, with Ca(2+) enriched in pam71 thylakoids
      relative to the wild type. The changes in Ca(2+) homeostasis were accompanied by
      an increased contribution of the transmembrane electrical potential to the proton
      motive force across the thylakoid membrane. PSII activity in pam71 plants and the
      corresponding Chlamydomonas reinhardtii mutant cgld1 was restored by
      supplementation with Mn(2+), but not Ca(2+) Furthermore, PAM71 suppressed the
      Mn(2+)-sensitive phenotype of the yeast mutant Deltapmr1 Therefore, PAM71
      presumably functions in Mn(2+) uptake into thylakoids to ensure optimal PSII
      performance.

PMID- 27020961
TI  - On the estimation of brain signal entropy from sparse neuroimaging data.
AB  - Multi-scale entropy (MSE) has been recently established as a promising tool for
      the analysis of the moment-to-moment variability of neural signals. Appealingly,
      MSE provides a measure of the predictability of neural operations across the
      multiple time scales on which the brain operates. An important limitation in the
      application of the MSE to some classes of neural signals is MSE's apparent
      reliance on long time series. However, this sparse-data limitation in MSE
      computation could potentially be overcome via MSE estimation across shorter time
      series that are not necessarily acquired continuously (e.g., in fMRI block
      designs). In the present study, using simulated, EEG, and fMRI data, we examined
      the dependence of the accuracy and precision of MSE estimates on the number of
      data points per segment and the total number of data segments. As hypothesized,
      MSE estimation across discontinuous segments was comparably accurate and precise,
      despite segment length. A key advance of our approach is that it allows the
      calculation of MSE scales not previously accessible from the native segment
      lengths. Consequently, our results may permit a far broader range of applications
      of MSE when gauging moment-to-moment dynamics in sparse and/or discontinuous
      neurophysiological data typical of many modern cognitive neuroscience study
      designs. 

PMID- 27020962
TI  - Digital microfluidics for spheroid-based invasion assays.
AB  - Cell invasion is a key process in tissue growth, wound healing, and tumor
      progression. Most invasion assays examine cells cultured in adherent monolayers,
      which fail to recapitulate the three-dimensional nuances of the tissue
      microenvironment. Multicellular cell spheroids have a three-dimensional (3D)
      morphology and mimic the intercellular interactions found in tissues in vivo,
      thus providing a more physiologically relevant model for studying the tissue
      microenvironment and processes such as cell invasion. Spheroid-based invasion
      assays often require tedious, manually intensive handling protocols or the use of
      robotic liquid handling systems, which can be expensive to acquire, operate, and
      maintain. Here we describe a digital microfluidic (DMUF) platform that enables
      formation of spheroids by the hanging drop method, encapsulation of the spheroids
      in collagen, and the exposure of spheroids to migration-modulating agents.
      Collagen sol-gel solutions up to 4 mg mL(-1), which form gels with elastic moduli
      up to ~50 kPa, can be manipulated on the device. In situ spheroid migration
      assays show that cells from human fibroblast spheroids exhibit invasion into
      collagen gels, which can be either enhanced or inhibited by the delivery of
      exogenous migration modulating agents. Exposing fibroblast spheroids to spheroid
      secretions from colon cancer spheroids resulted in a >100% increase in fibroblast
      invasion into the collagen gel, consistent with the cancer-associated fibroblast
      phenotype. These data show that DMUF can be used to automate the liquid handling
      protocols for spheroid-based invasion assays and create a cell invasion model
      that mimics the tissue microenvironment more closely than two-dimensional
      culturing techniques do. A DMUF platform that facilitates the creation and
      assaying of 3D in vitro tissue models has the potential to make automated 3D cell
      based assays more accessible to researchers in the life sciences. 

PMID- 27020963
TI  - [Syphilitic osteitis in an HIV-negative patient].
AB  - BACKGROUND: Secondary syphilis with skeletal involvement is rare; herein we
      report a case concerning an HIV-negative patient. PATIENTS AND METHODS: During
      the course of secondary syphilis, a 28-year-old male homosexual, HIV-negative and
      with no medical history, presented intense and localized headaches persisting
      despite three weeks of antibiotic therapy. Bone scintigraphy revealed three bone
      lesions evocative of syphilitic osteitis, for which prolonged antibiotic therapy
      was instituted. DISCUSSION: Few cases of syphilitic osteitis have been described
      in the recent literature and these are linked to haematogenous diffusion of
      Treponema pallidum. Skeletal disease is suggested when febrile bone pain is
      present. Bone scintigraphy remains the best diagnostic tool and treatment
      comprises prolonged penicillin G or ceftriaxone.

PMID- 27020964
TI  - Clinical experiences in primary and secondary immunodeficiencies and immune
      mediated conditions using Gammanorm((r)).
AB  - Treatment for primary and secondary immunodeficiency disorders focuses on
      prevention and management of infections, using immunoglobulin G (IgG) replacement
      therapy with regular intravenous or subcutaneous IgG (SCIG) infusions. SCIG
      therapy has many advantages including improved efficacy and tolerability,
      enhanced patient satisfaction and lower costs. A number of SCIG preparations are
      available, including Gammanorm((r)) (Octapharma AG), a ready-to-use 16.5% liquid
      preparation of IgG, with low viscosity, well suited to self-administration and a
      long history of use. Clinical experience with Gammanorm has shown that it is
      effective and well tolerated in children and adults, including pregnant women,
      for primary and secondary immunodeficiency disorders. Recent data also suggest
      SCIG may have a role in the treatment of certain immune-mediated conditions.

PMID- 27020965
TI  - Peripherally inserted central catheters (PICCs) in cancer patients under
      chemotherapy: A prospective study on the incidence of complications and overall
      failures.
AB  - BACKGROUND AND OBJECTIVES: The increasing use of peripherally inserted central
      venous catheters (PICCs) for chemotherapy has led to the observation of an
      elevated risk of complications and failures. This study investigates PICC
      failures in cancer patients. METHODS: A prospective study was conducted at a
      single cancer institution on 291 PICC placement for chemotherapy. The primary
      study outcome was PICC failure. RESULTS: Median follow-up was 119 days. PICC
      complications occurred in 72 patients (24.7%) and failures with removal in 44
      (15.1%). Reasons for failures were upper extremity deep venous thrombosis (UEDVT)
      12 (4.1%), central line associate bloodstream infection (CLABSI) 5 (1.7%) with an
      infection rate of 0.95 per 1,000 catheter days, exit site infection 9 (3.1%) with
      a rate of 1.46 per 1,000 catheter days, catheter dislodgment 11 (3.8%), and
      occlusion 7 (2.4%). Statistically significant risk factors were previous DVT (HR
      2.95, 95%CI 1.33-6.53), reason for PICC implant (HR 3.65, 95%CI 1.12-10.34) and 5
      fluorouracil, oxaliplatin and bevacizumab based chemotherapy (HR 3.11, 95%CI 1.17
      8.26). CONCLUSIONS: PICC is a safe venous device for chemotherapy delivery.
      Nevertheless, a 15% rate of failure has to be taken in account when planning PICC
      insertion for chemotherapy purposes. J. Surg. Oncol. 2016;113:708-714. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27020966
TI  - Absorbed dose measurements in the build-up region of flattened versus unflattened
      megavoltage photon beams.
AB  - This study evaluated absorbed dose measurements in the build-up region of
      conventional (FF) versus flattening filter-free (FFF) photon beams. The absorbed
      dose in the build-up region of static 6 and 10MV FF and FFF beams was measured
      using radiochromic film and extrapolation chamber dosimetry for single beams with
      a variety of field sizes, shapes and positions relative to the central axis.
      Removing the flattening filter generally resulted in slightly higher relative
      build-up doses. No considerable impact on the depth of maximum dose was found. 

PMID- 27020967
TI  - Assessing the feasibility of two hybrid MBR systems using PAC for removing macro
      and micropollutants.
AB  - The removal of 10 organic micropollutants (OMPs) was studied in two MBRs using
      different types of membrane (flat sheet microfiltration, MF, and hollow fiber
      ultrafiltration, UF) operated under aerobic conditions with direct dosing of
      powdered activated carbon (PAC) in the mixed liquor. In both reactors high COD
      degradation and nitrification were achieved (>95%), while nitrate removal was
      only observed after PAC addition. The adsorbent improved the operation of both
      systems (sludge properties and microbial diversity) which resulted in an
      enhancement of the quality of the final effluent. The operation with both types
      of membrane was feasible being the UF system slightly better in terms of the
      quality of the final effluent. The strategy of 250 mg/L of PAC additions every 35
      days was validated according to the results obtained for the removal of the most
      recalcitrant OMPs, such as diclofenac and carbamazepine. Concerning the type of
      membrane, only significant differences were observed for diclofenac and
      roxithromycin, which were better removed in the UF configuration. These
      differences were attributed to sorption and/or further biotransformation
      processes occurring in the cake layer.

PMID- 27020969
TI  - Why Publish?

PMID- 27020968
TI  - Comparative Gene Expression Analysis of the Coronal Pulp and Apical Pulp Complex
      in Human Immature Teeth.
AB  - INTRODUCTION: This study determined the gene expression profiles of the human
      coronal pulp (CP) and apical pulp complex (APC) with the aim of explaining
      differences in their functions. METHODS: Total RNA was isolated from the CP and
      APC, and gene expression was analyzed using complementary DNA microarray
      technology. Gene ontology analysis was used to classify the biological function.
      Quantitative reverse-transcription polymerase chain reaction and
      immunohistochemical staining were performed to verify microarray data. RESULTS:
      In the microarray analyses, expression increases of at least 2-fold were present
      in 125 genes in the APC and 139 genes in the CP out of a total of 33,297 genes.
      Gene ontology class processes found more genes related to immune responses, cell
      growth and maintenance, and cell adhesion in the APC, whereas transport and
      neurogenesis genes predominated in the CP. Quantitative reverse-transcription
      polymerase chain reaction and immunohistochemical staining confirmed the
      microarray results, with DMP1, CALB1, and GABRB1 strongly expressed in the CP,
      whereas SMOC2, SHH, BARX1, CX3CR1, SPP1, COL XII, and LAMC2 were strongly
      expressed in the APC. CONCLUSIONS: The expression levels of genes related to
      dentin mineralization, neurogenesis, and neurotransmission are higher in the CP
      in human immature teeth, whereas those of immune-related and tooth development
      related genes are higher in the APC.

PMID- 27020970
TI  - Football and Chronic Traumatic Encephalopathy: How Much Evidence Actually Exists?

PMID- 27020971
TI  - Serial Re-Expansion of Pituitary Gland Is Associated with Endocrinologic
      Recovery.
AB  - BACKGROUND: Minimizing pituitary dysfunction by preservation of the normal
      pituitary gland has a significant clinical impact on patient outcome after
      pituitary surgery. This study aimed to determine whether re-expansion of the
      healthy gland after surgery was related to endocrinologic outcome. METHODS: From
      January 2012 to July 2014, 112 patients were eligible for this retrospective
      study. Magnetic resonance imaging with dynamic contrast enhancement done2 days
      and 3 months before and after surgery was evaluated to assess the tumor and
      normal pituitary gland. We assessed the size of the pituitary gland and evaluated
      the relationship with endocrinologic outcome. RESULTS: The mean preoperative size
      of the gland was 3.86 mm, within 2 days after surgery it was 5.50 mm and 3 months
      after surgery it was 7.17 mm. Preoperatively patients were grouped based on their
      requirement of hormone replacement. Patients who required hormone replacement
      therapy before surgery and did not recover from hormonal insufficiency were
      classified as group 1 (26 patients), those who recovered from preoperative
      hormonal insufficiency and discontinued hormone replacement after surgery were
      classified as group 2 (17 patients), and those who showed hormonally normal
      status and did not need hormone replacement before and after surgery were in
      group 3 (68 patients). In group 1, the size of the gland expanded 1.24 times
      within postoperative 2 days but had no increase after 3 months (1.25 mm) (P =
      0.716). Group 2 showed a 1.30 times larger gland within postoperative 2 days and
      2.37 times at 3 months follow-up (P = 0.001). Group 3 showed 1.62 times larger
      gland at postoperative day 2 and 2.1 times larger at the 3-month follow-up.
      CONCLUSIONS: Serial re-expansion of the healthy pituitary gland at the 3-month
      follow-up magnetic resonance imaging can predict the endocrinologic recovery.

PMID- 27020972
TI  - Risk Factors for Newly Developed Cerebral Infarction After Surgical
      Revascularization for Adults with Moyamoya Disease.
AB  - OBJECTIVE: It is important to recognize the incidence and risk factors for
      ischemic complications after surgical revascularization for moyamoya disease
      (MMD). However, most studies focus on pediatric MMD or pediatric and adult MMD.
      Our study identified the incidence and risk factors of newly developed cerebral
      infarction after surgical revascularization for adult MMD. METHODS: Ischemic
      complications were defined as newly developed cerebral infarction within 15 days
      after surgery, as identified by imaging studies. To identify the incidence and
      these risk factors for adult patients >=18 years, we retrospectively reviewed our
      experience with 194 adult MMD patients with 241 surgical revascularizations.
      RESULTS: The incidence of symptomatic infarction after surgical revascularization
      was 5.8% (14 cases); 30 cases (12.4%) experienced a silent infarction. In
      univariate analysis, initial presentation as infarction, initial presentation as
      hemorrhage, transient ischemic attacks (TIAs) >3 times/month, involvement of the
      posterior cerebral artery (PCA), combined bypass, and using muscle for
      revascularization were variables related to the newly developed cerebral
      infarction. Multivariate analysis revealed that the following factors were
      independently associated with newly developed cerebral infarction after surgery:
      cerebral infarction as initial presentation (odds ratio [OR] 1.150; 95%
      confidence interval [CI] 1.038-1.273; P = 0.0073), TIAs >3times/month (OR 1.188;
      95% CI 1.058-1.335; P = 0.0035), and PCA involvement (OR 1.095; 95% CI 1.005
      1.194; P = 0.039). CONCLUSIONS: Our findings demonstrate that newly developed,
      silent cerebral infarction developed more frequently than symptomatic cerebral
      infarction in adult patients. Cerebral infarction as initial presentation,
      frequent TIA before surgery, and PCA involvement were also independent risk
      factors for newly developed cerebral infarction after surgical revascularization
      for adult MMD.

PMID- 27020973
TI  - Minimally Invasive Hemorrhage Evacuation.

PMID- 27020974
TI  - Effectiveness of Intraoperative Indocyanine Green Videoangiography in Avoiding
      Failure in Proximal Clipping for Dissecting Vertebral Artery Aneurysm Associated
      with Double Origin of the Posterior Inferior Cerebellar Artery.
AB  - BACKGROUND: Double origin of the posterior inferior cerebellar artery (PICA) is
      rarely reported but is associated with cerebral aneurysm and dissection. Such
      aneurysms and dissections with unusual anatomic dispositions present the surgeon
      or physician with difficulties during treatment. CASE DESCRIPTION: A 65-year-old
      man presented with severe subarachnoid hemorrhage caused by a left dissecting VA,
      which was treated with proximal clipping. No aberrant origin of the PICA was
      recognized on initial imaging. Dissecting VA was confirmed from mural
      discoloration and obliterated by clip application proximal to the dissection.
      However, the dissecting VA that should have been eliminated from the circulation
      was still depicted on indocyanine green videoangiography. Meticulous inspection
      revealed an aberrant branch connecting the VA with the PICA. Termination of the
      dissecting VA was accomplished by division of the aberrant stem of the PICA and
      was confirmed by indocyanine green videoangiography. CONCLUSIONS: Despite its
      rarity, the possibility of a double origin of the PICA should be considered when
      treating a dissecting VA. Missing a small aberrant origin of the PICA would lead
      to treatment failure but can be detected by indocyanine green videoangiography
      during open direct surgery.

PMID- 27020975
TI  - Postoperative Complications for Elderly Patients After Single-Level Lumbar
      Fusions for Spondylolisthesis.
AB  - OBJECTIVE: A large-scale study on postoperative complications of lumbar fusion
      surgery for spondylolisthesis comparing patients >80 years old with younger
      patients has not been performed. The purpose of this study is to assess the
      effects of extreme age (>80 years old) on early postoperative outcomes after
      single-level lumbar fusions for spondylolisthesis. METHODS: From a validated
      multicenter surgical database, 2475 patients who underwent a single-level lumbar
      fusion procedure for spondylolisthesis were selected retrospectively. An extreme
      age cohort with 227 patients >80 years old was compared with a typical age cohort
      with 2248 patients 45-65 years old. RESULTS: The preoperative characteristics and
      comorbidities were different between the typical age cohort and the extreme age
      cohort, with older patients having more preoperative comorbidities, including a
      lack of independent functional health status before surgery (P < 0.001), severe
      chronic obstructive pulmonary disease (P <0.020), and hypertension requiring
      medication (P < 0.001). There was significantly greater morbidity among the >80
      cohort regarding urinary tract infection (P = 0.008; odds ratio = 3.30; 95%
      confidence interval, 1.47-7.40) and intraoperative and postoperative transfusions
      (P < 0.001; odds ratio = 2.186; 95% confidence interval, 1.54-3.11). There was
      significantly greater morbidity among the younger cohort regarding cardiac arrest
      requiring cardiopulmonary resuscitation (P = 0.043; odds ratio = 0.099; 95%
      confidence interval, 0.014-0.704). CONCLUSIONS: This is the first large study
      comparing the rates of postoperative complications of lumbar fusion surgery for
      spondylolisthesis in patients >80 years old versus younger patients. The data
      support that age alone should not exclude a patient for this procedure. However,
      extra caution is warranted given the slightly increased morbidity.

PMID- 27020976
TI  - Necroptosis Pathway in Treatment of Intracerebral Hemorrhage: Novel Therapeutic
      Target.

PMID- 27020977
TI  - Rethinking Traumatic Brain Injury.

PMID- 27020978
TI  - The Implication of Anterior Communicating Complex Rotation and 3-Dimensional
      Computerized Tomography Angiography Findings in Surgical Approach to Anterior
      Communicating Artery Aneurysms.
AB  - BACKGROUND: To investigate the usefulness of 3-dimensional computerized
      tomography angiography (3D-CTA) in the microsurgical management of anterior
      communicating artery (AcomA) aneurysms. METHODS: Twenty-six consecutive patients
      with AcomA aneurysms (22 ruptured) underwent microsurgical clipping. Detailed
      angioanatomic assessment of the AcomA complex and operative approach was based on
      the 3D-CTA. RESULTS: The 3D-CTA showed a dominant proximal anterior cerebral
      artery (A1) segment in 61% and symmetric A1s in 39% of aneurysms. Dominant A1
      segments presented with rotation of the AcomA complex toward the contralateral
      side in 63%, toward the ipsilateral side in 25%, and without rotation in 12%.
      With symmetric A1s, the AcomA was parallel to the coronal plane in 90% and a
      right-sided approach was carried out in these patients. In rotated AcomA
      complexes, the virtual 3D views were compared to determine the side of the
      approach. For superior projecting aneurysms, we determined that the approach from
      the side in which the A1-distal anterior cerebral artery (posterior
      communicating) angle was posterior was more favorable. For posterior projecting
      aneurysms, the approach from the side where the A1-distal anterior cerebral
      artery (posterior communicating) angle was more anterior was more favorable. For
      anteroinferior projecting aneurysms, an approach from the dominant A1 side was
      chosen regardless of AcomA complex rotation. Postoperative 3D-CTA showed complete
      exclusion of 24 aneurysms (>92%) and 2 small remnants (<2 mm). Outcome was
      excellent or good (modified Rankin score 0-2) in 88% of patients. CONCLUSIONS:
      Rotation of the AcomA complex and dome projection are important angioanatomic
      elements in determining the surgical exposure and side of the approach. This
      study illustrates the role of 3D-CTA in the management of these difficult lesions
      by individualizing the surgical approach.

PMID- 27020979
TI  - Refinement of the Hybrid Neuroendovascular Operating Suite: Current and Future
      Applications.
AB  - OBJECTIVE: In early-generation hybrid biplane endovascular operating rooms,
      switching from surgical to angiographic position is cumbersome. In this report,
      we highlight the unique design of a new hybrid neuroendovascular operating suite
      that allows surgical access to the head while keeping the biplane system over the
      lower body of the patient. Current and future hybrid neuroendovascular operating
      suite applications are discussed. METHODS: We collaborated with engineers to
      implement the following modifications to the design of the angiographic system:
      translation of the bed toward the feet to allow biplane cerebral imaging in the
      head-side position and the biplane left-side position; translation of the base of
      the A-plane C-arm away from the feet to allow increased operator space at the
      head of the bed and to allow cerebral imaging in both the head-side and left-side
      positions; use of a specialized boom mount for the display panel to increase
      mobility; and use of a radiolucent tabletop with attachments for the headrest or
      radiolucent head clamp system. RESULTS: The modified hybrid neuroendovascular
      operating suite allows for seamless transition between surgical and angiographic
      positions within seconds, improving workflow efficiency and decreasing procedure
      time as compared with early-generation hybrid rooms. CONCLUSIONS: Combined
      endovascular and surgical applications are facilitated by co-locating their
      respective technologies and refining the ergonomics of the system to ease
      transition between both sets of technologies. In so doing, hybrid
      neuroendovascular operating suites can be anticipated to improve patient
      outcomes, generate novel treatment paradigms, and improve time and cost
      efficiency.

PMID- 27020980
TI  - Recent Advances in the Concept of Radiation Therapy of Brain Metastases: Dawn of
      the Radiosurgery Era.

PMID- 27020981
TI  - Uncovering a New Cause of Obstructive Hydrocephalus Following Subarachnoid
      Hemorrhage: Choroidal Artery Vasospasm-Related Ependymal Cell Degeneration and
      Aqueductal Stenosis-First Experimental Study.
AB  - BACKGROUND: Hydrocephalus is a serious complication of subarachnoid hemorrhage
      (SAH). Obstruction of the cerebral aqueduct may cause hydrocephalus after SAH.
      Although various etiologic theories have been put forward, choroidal artery
      vasospasm-related ependymal desquamation and subependymal basal membrane rupture
      as mechanisms of aqueductal stenosis have not been suggested in the literature.
      METHODS: This study was conducted on 26 hybrid rabbits. Five rabbits were placed
      in a control group, 5 were placed in a sham group, and the remaining rabbits (n =
      16) were placed in the SAH group. In the first 2 weeks, 5 animals in the SAH
      group died. The other 21 animals were decapitated after the 4-week follow-up
      period. Choroidal artery changes resulting from vasospasm, aqueduct volume,
      ependymal cell density, and Evans index values of brain ventricles were obtained
      and compared statistically. RESULTS: Mean aqueduct volume was 1.137 mm(3) +/-
      0.096, normal ependymal cell density was 4560/mm(2) +/- 745, and Evans index was
      0.32 +/- 0.05 in control animals (n = 5); these values were 1.247 mm(3) +/-
      0.112, 3568/mm(2) +/- 612, and 0.34 +/- 0.15 in sham animals (n = 5); 1.676 mm(3)
      +/- 0.123, 2923/mm(2) +/- 591, and 0.43 +/- 0.09 in animals without aqueductal
      stenosis (n = 5); and 0.650 mm(3) +/- 0.011, 1234/mm(2) +/- 498, and 0.60 +/-
      0.18 in animals with severe aqueductal stenosis (n = 6). The choroidal vasospasm
      index values were 1.160 +/- 0.040 in the control group, 1.150 +/- 0.175 in the
      sham group, 1.760 +/- 0.125 in the nonstenotic group, and 2.262 +/- 0.160 in the
      stenotic group. Aqueduct volumes, ependymal cell densities, Evans index, and
      choroidal artery vasospasm index values were statistically significantly
      different between groups (P < 0.05). CONCLUSIONS: Ependymal cell desquamation and
      subependymal basal membrane destruction related to choroidal artery vasospasm may
      lead to aqueductal stenosis and hydrocephalus after SAH.

PMID- 27020982
TI  - The Ontogeny and Microenvironmental Regulation of Tumor-Associated Macrophages.
AB  - SIGNIFICANCE: Tumor progression is supported by non-cancerous stromal cells, of
      which tumor-associated macrophages (TAMs) are prominent constituents. These cells
      could be considered promising therapeutic targets, but this requires a better
      understanding of their heterogeneity under the influence of tumor
      microenvironmental cues and/or ontogenic differences. Recent Advances: The
      availability of oxygen is an important regulator of the TAM phenotype, as well as
      of its access to myelopoietic growth factors. Very recent evidence also
      demonstrated that macrophages can be derived from embryonal precursors or from
      monocytes post-birth, introducing yet another level of heterogeneity among
      macrophages. CRITICAL ISSUES: The relative contribution of ontogenically distinct
      macrophages to tumor characteristics is, to a large extent, still an open
      question. In addition, further knowledge on the role of tumor microenvirontal
      cues that shape TAMs is warranted. FUTURE DIRECTIONS: More detailed insights into
      the TAM-regulating factors will provide new opportunities for therapeutic
      intervention. Interference with the phenotypes of TAM, which are known to be
      immunosuppressive and to contribute to dysfunctional tumor blood vessels, is
      anticipated to be beneficial in combination with chemotherapy and/or
      immunotherapy. Antioxid. Redox Signal. 25, 775-791.

PMID- 27020983
TI  - Cost-Savings Analysis of Renal Scintigraphy, Stratified by Renal Function
      Thresholds: Mercaptoacetyltriglycine Versus Diethylene Triamine Penta-Acetic
      Acid.
AB  - PURPOSE: To determine the financial implications of switching technetium (Tc)-99m
      mercaptoacetyltriglycine (MAG-3) to Tc-99m diethylene triamine penta-acetic acid
      (DTPA) at certain renal function thresholds before renal scintigraphy. METHODS:
      Institutional review board approval was obtained, and informed consent was waived
      for this HIPAA-compliant, retrospective, cohort study. Consecutive adult subjects
      (27 inpatients; 124 outpatients) who underwent MAG-3 renal scintigraphy, in the
      period from July 1, 2012 to June 30, 2013, were stratified retrospectively by
      hypothetical serum creatinine and estimated glomerular filtration rate (eGFR)
      thresholds, based on pre-procedure renal function. Thresholds were used to
      estimate the financial effects of using MAG-3 when renal function was at or worse
      than a given cutoff value, and DTPA otherwise. Cost analysis was performed with
      consideration of raw material and preparation costs, with radiotracer costs
      estimated by both vendor list pricing and proprietary institutional pricing. The
      primary outcome was a comparison of each hypothetical threshold to the clinical
      reality in which all subjects received MAG-3, and the results were supported by
      univariate sensitivity analysis. RESULTS: Annual cost savings by serum creatinine
      threshold were as follows (threshold given in mg/dL): $17,319 if >=1.0; $33,015
      if >=1.5; and $35,180 if >=2.0. Annual cost savings by eGFR threshold were as
      follows (threshold given in mL/min/1.73 m(2)): $21,649 if <=60; $28,414 if <=45;
      and $32,744 if <=30. Cost-savings inflection points were approximately 1.25 mg/dL
      (serum creatinine) and 60 mL/min/1.73m(2) (eGFR). Secondary analysis by
      proprietary institutional pricing revealed similar trends, and cost savings of
      similar magnitude. Sensitivity analysis confirmed cost savings at all tested
      thresholds. CONCLUSIONS: Reserving MAG-3 utilization for patients who have
      impaired renal function can impart substantial annual cost savings to a radiology
      department.

PMID- 27020984
TI  - pH-Responsive Polymer Conjugate of Pirarubicin With Styrene Maleic Acid Copolymer
      as a Potential Therapeutic for Ovarian Cancer.
AB  - Previous studies indicated the potential of styrene maleic acid copolymer (SMA)
      conjugated pirarubicin (4'-O-tetrahydropyranyldoxorubicin [THP]) for targeted
      anticancer therapy based on the enhanced permeability and retention effect. In
      this study, to achieve further improved therapeutic efficacy, a pH-responsive SMA
      conjugated THP-containing hydrazone bond (SMA-hyd-THP) was synthesized and
      evaluated in vitro and ex vivo using human ovarian cancer cells and tissues. SMA
      hyd-THP showed good water solubility, forming micelles with a mean particle size
      of 48.0 nm, which is applicable for enhanced permeability and retention-based
      tumor accumulation. The THP loading in this preparation was 15% (wt/wt), and
      release rate of free THP from SMA-hyd-THP at physiological pH (7.4) was
      approximately 10% in 72 h. However, it increased rapidly at pH 6.5 (42%) and 5.5
      (83%), which indicates that tumor environment of weak acidic condition (pH 6.5
      6.9) is favorable for release of THP. This notion was partly proved by incubating
      SMA-hyd-THP with tumor tissues from ovarian cancer patients. In addition, release
      of THP was not affected by serum, suggesting that SMA-hyd-THP is relatively
      stable in circulation. Finally, SMA-hyd-THP showed much increased cytotoxicity
      against various ovarian cancer cells at acidic tumor pH (6.5). These findings may
      provide an option for targeted therapy against ovarian cancer.

PMID- 27020985
TI  - The Evaluation of In Vitro Drug Dissolution of Commercially Available Oral Dosage
      Forms for Itraconazole in Gastrointestinal Simulator With Biorelevant Media.
AB  - The purpose of this study was to assess the feasibility of a multicompartmental
      in vitro dissolution apparatus, gastrointestinal simulator (GIS), in assessing
      the drug dissolution of 2 commercially available oral dosage forms for
      itraconazole (ICZ). The GIS consists of 3 chambers, mimicking the upper
      gastrointestinal tract. In vitro dissolution of ICZ capsule or oral solution was
      evaluated in United States Pharmacopeia apparatus II and GIS. To investigate the
      suitability of fasted state simulated intestinal fluid (FaSSIF) to predict better
      in vivo, FaSSIF as well as phosphate buffer were used as dissolution media. Area
      under the dissolved drug amount-time curve (AUDC) was calculated for each dosage
      form in each apparatus, and the ratios of AUDCoral solution to AUDCcapsule were
      compared with human pharmacokinetic data. Based on this comparison, GIS with
      FaSSIF can adequately distinguish the pharmacokinetic profiles of 2 oral dosage
      forms for ICZ. Additionally, Caco-2 cell transepithelial transport study in
      combination with GIS revealed that improved drug dissolution by formulations
      resulted in enhanced permeation of ICZ through cell monolayer, suggesting the
      observed ICZ concentration in the GIS will directly reflect systemic exposure.
      These results indicate GIS would be a powerful tool to assess the formulations of
      ICZ as well as other Biopharmaceutics Classification System class II drug
      formulations.

PMID- 27020986
TI  - Localization of Xenobiotic Transporter OCTN1/SLC22A4 in Hepatic Stellate Cells
      and Its Protective Role in Liver Fibrosis.
AB  - Xenobiotic transporters play key roles in disposition of certain therapeutic
      agents, although limited information is available on their roles other than
      pharmacokinetic issues. Here, suppressive effect of multispecific organic cation
      transporter OCTN1/SLC22A4 on liver fibrosis was proposed in liver injury models.
      After injection of hepatotoxins such as dimethylnitrosamine (DMN) or concanavalin
      A, hepatic fibrosis, and oxidative stress, evaluated in terms of Sirius red and 4
      hydroxy-2-nonenal staining, respectively, were more severe in liver of
      octn1/slc22a4 gene knockout (octn1(-/-)) mice than that in wild-type mice. DMN
      treatment markedly increased alpha-smooth muscle actin and F4/80, markers of
      activated stellate and Kupffer cells, respectively, in liver of octn1(-/-), but
      had less effect in wild-type mice. Thus, octn1/slc22a4 gene deletion results in
      more severe hepatic fibrosis, oxidative stress, and inflammation. DMN-treated
      wild-type mice showed increased Octn1 staining and hepatic concentration of its
      food-derived antioxidant ergothioneine (ERGO). The upregulated Octn1 was co
      localized with alpha-smooth muscle actin. Functional expression of Octn1 was
      demonstrated in activated human hepatic stellate cell lines, LI90 and LX-2.
      Provision of ERGO-rich feed ameliorated DMN-induced liver fibrosis and oxidative
      stress. Overall, Octn1 is upregulated in activated stellate cells, resulting in
      increased delivery of its substrate antioxidant ERGO and a protective effect
      against liver fibrosis.

PMID- 27020988
TI  - How relevant is refeeding syndrome?

PMID- 27020989
TI  - Zika virus and the current outbreak: an overview.
AB  - Zika virus (ZIKV), a mosquito-borne flavivirus closely related to yellow fever
      virus and dengue virus, is currently causing a large outbreak in the Americas.
      Historically, ZIKV infection was considered a sporadic, relatively mild disease
      characterised by fever, maculopapular rash, conjunctivitis and often arthralgia.
      However, current observational studies suggest that ZIKV may cause more severe
      neurological sequelae such as Guillain-Barre syndrome, and birth defects, mainly
      microcephaly, in babies of whom the mother was infected with ZIKV during
      pregnancy. This article provides a clinically focussed overview of ZIKV, with
      emphasis on the current outbreak, clinical manifestations, diagnostic tools and
      caveats. 

PMID- 27020987
TI  - Silicone Oil Microdroplets Can Induce Antibody Responses Against Recombinant
      Murine Growth Hormone in Mice.
AB  - Therapeutic protein products can cause adverse immune responses in patients. The
      presence of subvisible particles is a potential contributing factor to the
      immunogenicity of parenterally administered therapeutic protein formulations.
      Silicone oil microdroplets, which derive from silicone oil used as a lubricating
      coating on barrels of prefilled glass syringes, are often found in formulations.
      In this study, we investigated the potential of silicone oil microdroplets to act
      as adjuvants to induce an immune response in mice against a recombinant murine
      protein. Antibody responses in mice to subcutaneous injections of formulations of
      recombinant murine growth hormone (rmGH) that contained silicone oil
      microdroplets were measured and compared to responses to oil-free rmGH
      formulations. When rmGH formulations containing silicone oil microdroplets were
      administered once every other week, anti-rmGH antibodies were not detected. In
      contrast, mice exhibited a small IgG1 response against rmGH when silicone oil
      containing rmGH formulations were administered daily, and an anti-rmGH IgM
      response was observed at later time points. Our findings showed that silicone oil
      microdroplets can act as an adjuvant to promote a break in immunological
      tolerance and induce antibody responses against a recombinant self-protein.

PMID- 27020990
TI  - An inflammatory condition with different faces: immunoglobulin G4-related
      disease.
AB  - BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro
      inflammatory condition with involvement of different organs. The
      pathophysiological mechanism is unclear, but fibrosis is the hallmark of this
      disease. Early recognition is critical to avoid irreversible organ damage.
      Recently improved histological testing boosts the diagnostic yield. We present
      three cases of patients with IgG4-RD to emphasise the broad clinical presentation
      of this disease. CASE DESCRIPTIONS: Patient A, a 63-year-old male with bilateral
      orbital swelling due to IgG4-RD, was shown to suffer from IgG4-RD in a multifocal
      pattern as demonstrated by PET scanning. Patient B, a 53-year-old male with a
      long-standing abdominal mass of unknown origin, eventually proved to have IgG4
      RD. Patient C was a 32-year-old male admitted with pleural effusion and
      pericardial tamponade. Histological diagnosis after pericardiectomy confirmed
      IgG4-RD. DISCUSSION: IgG4-RD has many faces and may mimic other conditions, such
      as malignancy and infectious diseases. Knowledge of this disease is needed to
      avoid unnecessary diagnostics and delay in treatment. IgG4- RD may be suspected
      based on specific clinical findings such as elevated serum IgG4 levels, but the
      diagnosis can only be established histologically. Although corticosteroids are an
      effective first choice of therapy, the relapse rate after this treatment remains
      high. The role of disease-modifying antirheumatic drugs in the treatment of IgG4
      RD has not been outlined yet, but there is increasing evidence that rituximab
      might be an effective second-line therapy. CONCLUSION: IgG4-RD is a disease with
      many faces requiring early recognition and therapy to avoid permanent damage of
      the organs.

PMID- 27020991
TI  - Incidence of refeeding syndrome in internal medicine patients.
AB  - BACKGROUND: Refeeding syndrome is a potentially fatal shift of fluids and
      electrolytes that may occur after reintroducing nutrition in a malnourished
      patient. Its incidence in internal medicine patients is not known. We aimed at
      determining the incidence in a heterogeneous group of patients acutely admitted
      to a department of internal medicine. METHODS: All patients acutely admitted to
      the department of internal medicine of a teaching community hospital in
      Amsterdam, the Netherlands, between 22 February 2011 and 29 April 2011, were
      included. We applied the National Institute for Health and Care Excellence (NICE)
      criteria for determining people at risk of refeeding syndrome and took
      hypophosphataemia as the main indicator for the presence of this syndrome.
      RESULTS: Of 178 patients included in the study, 97 (54%) were considered to be at
      risk of developing refeeding syndrome and 14 patients actually developed the
      syndrome (14% of patients at risk and 8% of study population). Patients with a
      malignancy or previous malignancy were at increased risk of developing refeeding
      syndrome (p < 0.05). Measurement of muscle strength over time was not associated
      with the occurrence of refeeding syndrome. The Short Nutritional Assessment
      Questionnaire score had a positive and negative predictive value of 13% and 95%
      respectively. CONCLUSION: The incidence of refeeding syndrome was relatively high
      in patients acutely admitted to the department of internal medicine. Oncology
      patients are at increased risk of developing refeeding syndrome. When taking the
      occurrence of hypophosphataemia as a hallmark, no other single clinical or
      composite parameter could be identified that accurately predicts the development
      of refeeding syndrome.

PMID- 27020992
TI  - The beneficial local and abscopal effect of splenic irradiation in frail patients
      with chronic lymphocytic leukaemia.
AB  - BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a common haematological
      malignancy that mainly occurs in the elderly population. Patients frequently have
      comorbidities compromising the use of old and new systemic therapies. METHODS AND
      RESULTS: We report the prevalence of comorbidities in patients with CLL as
      present in the southern region of the Netherlands Cancer Registry. Comorbid
      conditions were present in 67% of the male and 63% of the female patients, and
      became more common with increasing age. Furthermore, we describe the beneficial
      local and abscopal effects of splenic irradiation in four patients with CLL who
      were not suitable for systemic chemoimmunotherapy because of severe
      comorbidities, or who were unwilling to undergo systemic therapy. CONCLUSION: Our
      results show that, although an old tool, splenic irradiation should not be
      forgotten as a potentially effective palliative treatment option in frail
      patients with symptomatic CLL.

PMID- 27020993
TI  - The atopic heart: a curious case of coronary hypersensitivity.
AB  - Kounis syndrome is a coronary hypersensitivity disorder involving coronary
      vasospasm secondary to inflammatory mediators released primarily from mast cells.
      We report a case of the type I variant of Kounis syndrome manifesting as
      angioedema with significant inferolateral ST elevation (2 mm) and raised cardiac
      biomarkers. Diagnosis requires a high index of suspicion and treatment is
      tactical. Caution should be exercised before using beta-blockers, morphine and
      epinephrine, which are empiric in cases of acute coronary syndrome and
      anaphylaxis, respectively. Our patient was treated with intravenous steroids and
      histamine blockers given the angioedema at presentation. The purpose of our case
      is to emphasise the importance of including Kounis syndrome in the differential
      diagnosis for acute coronary syndrome, and formulation of standard treatment
      guidelines for this under-recognised condition. 

PMID- 27020994
TI  - A 45-year-old woman with an anticholinergic toxidrome.
AB  - Intentional or accidental intoxications are common in the emergency department,
      but are not always sufficiently recognised. When intoxication is suspected, the
      causative agent or combination of agents often remain unclear, making these
      patients a diagnostic challenge. We present here a 45-year-old woman who was
      admitted due to altered consciousness. The clinical presentation fitted the
      anticholinergic toxidrome and an intoxication with venlafaxine (her known
      prescribed medication) was suspected. Plasma venlafaxine concentrations, however,
      were very low. After 24 hours the patient recovered completely. Further testing
      after discharge revealed high concentrations of promethazine, confirming the
      suspected diagnosis. This case illustrates the importance of knowledge of
      toxidromes and good collaboration with the hospital pharmacist. Because of the
      thorough testing the patient could receive proper treatment. 

PMID- 27020995
TI  - A 39-year-old woman with a mushroom intoxication. Amanita phalloides.

PMID- 27020997
TI  - An unusual manifestation of diabetic ketoacidosis. Spontaneous pneumomediastinum.

PMID- 27020999
TI  - A rare complication of pneumonia. Infectious purulent pericarditis.

PMID- 27021001
TI  - Reactions and complications to bites. Bedbug, Cimex lectularius.

PMID- 27021003
TI  - First case of type IV hypersensitivity to periocular topotecan.

PMID- 27021004
TI  - Inhibition of phospho-MurNAc-pentapeptide translocase (MraY) by nucleoside
      natural product antibiotics, bacteriophage phiX174 lysis protein E, and cationic
      antibacterial peptides.
AB  - This review covers recent developments in the inhibition of translocase MraY and
      related phospho-GlcNAc transferases WecA and TagO, and insight into the
      inhibition and catalytic mechanism of this class of integral membrane proteins
      from the structure of Aquifex aeolicus MraY. Recent studies have also identified
      a protein-protein interaction site in Escherichia coli MraY, that is targeted by
      bacteriophage phiX174 lysis protein E, and also by cationic antimicrobial
      peptides containing Arg-Trp close to their N- or C-termini.

PMID- 27021005
TI  - Immobilization of two organometallic complexes into a single cage to construct
      protein-based microcompartments.
AB  - Natural protein-based microcompartments containing multiple enzymes promote
      cascade reactions within cells. We use the apo-ferritin protein cage to mimic
      such biocompartments by immobilizing two organometallic Ir and Pd complexes into
      the single protein cage. Precise locations of the metals and their accumulation
      mechanism were studied by X-ray crystallography. 

PMID- 27021006
TI  - Increased Serum Uric Acid Levels Blunt the Antihypertensive Efficacy of Lifestyle
      Modifications in Children at Cardiovascular Risk.
AB  - Primary hypertension is a growing concern in children because of the obesity
      epidemic largely attributable to western lifestyles. Serum uric acid is known to
      be influenced by dietary habits, correlates with obesity, and could represent a
      risk factor for hypertension. Preliminary studies in children highlighted uric
      acid as a potentially modifiable risk factor for the prevention and treatment of
      hypertension. The effect of lifestyle changes (increase of physical activity and
      dietary modifications) on blood pressure values, weight status, and serum uric
      acid levels in a cohort of 248 children referred for cardiovascular risk
      assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of
      children were obese and 50% showed blood pressure values >90th percentile. At
      follow-up, a significant improvement in weight class (24% obese;P<0.0001) and
      blood pressure category (22% >90th percentile;P<0.0001) was found. Systolic blood
      pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline
      (P=0.0048) were independently associated with higher systolic blood pressure z
      score at follow-up, whereas a negative association was observed with body mass
      index z-score decrease during follow-up (P=0.0033). The risk of hypertension at
      follow-up was associated with body mass index (P=0.0025) and systolic blood
      pressure (P<0.0001) z-score at baseline and inversely related to delta body mass
      index (P=0.0002), whereas the risk of showing hypertension >=99th percentile was
      more than doubled for each baseline 1 mg/dL increase of serum uric acid
      (P=0.0130). Uric acid is a powerful determinant of blood pressure over time,
      independent of lifestyle modifications.

PMID- 27021007
TI  - Cardiac-Specific EPI64C Blunts Pressure Overload-Induced Cardiac Hypertrophy.
AB  - The calcium-responsive molecule, calcineurin, has been well characterized to play
      a causal role in pathological cardiac hypertrophy over the past decade. However,
      the intrinsic negative regulation of calcineurin signaling during the progression
      of cardiomyocyte hypertrophy remains enigmatic. Herein, we explored the role of
      EPI64C, a dual inhibitor of both Ras and calcineurin signaling during T-cell
      activation, in pressure overload-induced cardiac hypertrophy. We generated a
      cardiac-specific Epi64c conditional knockout mouse strain and showed that loss of
      Epi64c remarkably exacerbates pressure overload-induced cardiac hypertrophy. In
      contrast, EPI64C gain-of-function in cardiomyocyte-specific Epi64c transgenic
      mice exerts potent protective effects against cardiac hypertrophy.
      Mechanistically, the cardioprotective effects of EPI64C are largely attributed to
      the disrupted calcineurin signaling but are independent of its Ras suppressive
      capability. Molecular studies have indicated that the 406 to 446 C-terminal amino
      acids in EPI64C directly bind to the 287 to 337 amino acids in the catalytic
      domain of calcineurin, which is responsible for the EPI64C-mediated suppressive
      effects. We further extrapolated our studies to cynomolgus monkeys and showed
      that gene therapy based on lentivirus-mediated EPI64C overexpression in the
      monkey hearts blunted pressure overload-induced cardiac hypertrophy. Our study
      thus identified EPI64C as a novel negative regulator in cardiac hypertrophy by
      targeting calcineurin signaling and demonstrated the potential of gene therapy
      and drug development for treating cardiac hypertrophy.

PMID- 27021008
TI  - Angiotensin II Type 2-Receptor Agonist C21 Reduces Proteinuria and Oxidative
      Stress in Kidney of High-Salt-Fed Obese Zucker Rats.
AB  - Oxidative and nitrosative stress have been implicated in high-sodium diet (HSD)
      related hypertensive renal injury. In this study, we investigated angiotensin II
      type 2-receptor-mediated renoprotection in obese Zucker rats fed HSD. Obese
      Zucker rats were fed normal sodium diet or HSD 4%, for 14 days, with/without
      angiotensin II type 2-receptor agonist C21, delivered subcutaneously via osmotic
      pump, 1 mg/kg per day. Compared with normal sodium diet controls, HSD rats
      exhibited increase in cortical nicotinamide adenine dinucleotide phosphate
      oxidase activity, urinary H2O2, and 8-isoprostanes, which were associated with
      severe glomerulosclerosis, interstitial fibrosis, decline in estimated glomerular
      filtration rate, and an increase in urinary leak and activity of N-acetyl-beta-D
      glucosaminidase, a lysosomal enzyme and a marker of tubular damage. These changes
      were improved by C21 treatment. Cortical expression of endothelial nitric oxide
      synthase, phospho-endothelial nitric oxide synthase (Ser(1177)), and plasma
      nitrites were reduced after HSD intake, whereas nitrosative stress (3
      nitrotyrosine) and enzymatic defense (superoxide dismutase-to-catalase activity)
      remained unaltered. However, C21 preserved plasma nitrites in HSD-fed obese
      Zucker rat. C21 treatment reduced protein-to-creatinine, albumin-to-creatinine,
      as well as fractional excretion of protein and albumin in HSD-fed obese Zucker
      rat, which is independent of changes in protein recycling receptors, megalin, and
      cubilin. HSD intake also altered renal excretory and reabsorptive capacity as
      evident by elevated plasma urea nitrogen-to-creatinine and fractional excretion
      of urea nitrogen, and reduced urine-to-plasma creatinine, which were modestly,
      but insignificantly, improved by C21 treatment. Together results demonstrate that
      angiotensin II type 2-receptor activation protects against HSD-induced kidney
      damage in obesity plausibly by reducing nicotinamide adenine dinucleotide
      phosphate oxidase activity and rescuing nitrites.

PMID- 27021009
TI  - Sympathetic Neural and Hemodynamic Responses During Cold Pressor Test in Elderly
      Blacks and Whites.
AB  - The sympathetic response during the cold pressor test (CPT) has been reported to
      be greater in young blacks than whites, especially in those with a family history
      of hypertension. Because blood pressure (BP) increases with age, we evaluated
      whether elderly blacks have greater sympathetic activation during CPT than age
      matched whites. BP, heart rate, cardiac output, and muscle sympathetic nerve
      activity were measured during supine baseline, 2-minute CPT, and 3-minute
      recovery in 47 elderly (68 +/- 7 [SD] years) volunteers (12 blacks and 35
      whites). Baseline BP, heart rate, cardiac output, or muscle sympathetic nerve
      activity did not differ between races. Systolic and diastolic BP and heart rate
      increased during CPT (all P<0.001) with no racial differences (all P > 0.05).
      Cardiac output increased during CPT and <= 30 s of recovery in both groups, but
      was lower in blacks than whites. Muscle sympathetic nerve activity increased
      during CPT in both groups (both P<0.001); the increase in burst frequency was
      similar between groups, whereas the increase in total activity was smaller in
      blacks (P=0.030 for interaction). Peak change (Delta) in diastolic BP was
      correlated with Delta total activity at 1 minute into CPT in both blacks
      (r=0.78,P=0.003) and whites (r=0.43,P=0.009), whereas the slope was significantly
      greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and
      central hemodynamic (eg, cardiac output) responses, but a greater pressor
      response for a given sympathetic activation during CPT than elderly whites. This
      response may stem from augmented sympathetic vascular transduction, greater
      sympathetic activation to other vascular bed(s), or enhanced nonadrenergically
      mediated vasoconstriction in elderly blacks.

PMID- 27021010
TI  - Leptin Mediates High-Fat Diet Sensitization of Angiotensin II-Elicited
      Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation.
AB  - Obesity is characterized by increased circulating levels of the adipocyte-derived
      hormone leptin, which can increase sympathetic nerve activity and raise blood
      pressure. A previous study revealed that rats fed a high-fat diet (HFD) have an
      enhanced hypertensive response to subsequent angiotensin II administration that
      is mediated at least, in part, by increased activity of brain renin-angiotensin
      system and proinflammatory cytokines. This study tested whether leptin mediates
      this HFD-induced sensitization of angiotensin II-elicited hypertension by
      interacting with brain renin-angiotensin system and proinflammatory cytokine
      mechanisms. Rats fed an HFD for 3 weeks had significant increases in white
      adipose tissue mass, plasma leptin levels, and mRNA expression of leptin and its
      receptors in the lamina terminalis and hypothalamic paraventricular nucleus.
      Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD
      sensitization of angiotensin II-elicited hypertension. Furthermore, central
      infusion of leptin mimicked the sensitizing action of HFD. Concomitant central
      infusions of the angiotensin II type 1 receptor antagonist irbesartan, the tumor
      necrosis factor-alpha synthesis inhibitor pentoxifylline, or the inhibitor of
      microglial activation minocycline prevented the sensitization produced by central
      infusion of leptin. RT-PCR analysis indicated that either HFD or leptin
      administration upregulated mRNA expression of several components of the renin
      angiotensin system and proinflammatory cytokines in the lamina terminalis and
      paraventricular nucleus. The leptin antagonist and the inhibitors of angiotensin
      II type 1 receptor, tumor necrosis factor-alpha synthesis, and microglial
      activation all reversed the expression of these genes. The results suggest that
      HFD-induced sensitization of angiotensin II-elicited hypertension is mediated by
      leptin through upregulation of central renin-angiotensin system and
      proinflammatory cytokines. 

PMID- 27021011
TI  - Is the SPRINT Blood Pressure Treatment Target of 120/80 mm Hg Relevant for
      Children?

PMID- 27021012
TI  - Serum Uric Acid in Primary Hypertension: From Innocent Bystander to Primum
      Movens?

PMID- 27021013
TI  - Positive Role for a Negative Calcineurin Regulator in Cardiac Hypertrophy.

PMID- 27021014
TI  - Say NO to Obesity-Related Hypertension: Role of the L-Arginine-Nitric Oxide
      Pathway.

PMID- 27021015
TI  - To Sensitize or Not to Sensitize: Leptin Is the Question.

PMID- 27021016
TI  - Perirhinal cortex supports tactual discrimination tasks with increasing levels of
      complexity: Retrograde effect.
AB  - Recent studies have suggested that the perirhinal cortex (Prh) supports
      representations of feature conjunctions in the visual modality during the
      acquisition/encoding of complex discriminations. To extend this idea to other
      sensory modalities and to another stage of the discrimination process, we studied
      the effect of Prh lesions on the expression of a series of tactual discrimination
      tasks learned preoperatively. These tasks differed from one another in the degree
      of feature overlap of the stimuli and in the difficulty of the task. During pre-
      and post-operative testing phases, rats had to discriminate among 3 stimuli
      simultaneously exposed in 3 arms of a 4-arm plus-shaped maze. Prh-damaged rats
      showed a profound impairment in the expression of tactual discrimination tasks
      when the stimuli had a high or intermediate degree of feature ambiguity, but not
      when they had a low degree of ambiguity (experiments 1a-1c). In order to
      experimentally dissociate between subregions within the medial temporal lobe,
      experiment 2 was conducted to show that hippocampal lesions did not cause any
      impairment in task expression even when the stimuli had a high degree of feature
      ambiguity. When the tactual discrimination tasks used simple/individual
      nonoverlapping features of the stimuli (size), Prh lesions did not affect the
      expression of these discriminations despite the high level of difficulty of these
      tasks (experiments 3a and 3b). These findings suggest that, in the somatosensory
      modality, the Prh plays an essential role in the processing of complex stimuli
      with overlapping features but not in simple tactual discriminations. Furthermore,
      the Prh is necessary not just during acquisition but also during
      expression/performance of the discrimination task.

PMID- 27021017
TI  - Daytime sleep has no effect on the time course of motor sequence and visuomotor
      adaptation learning.
AB  - Sleep has previously been claimed to be essential for the continued learning
      processes of declarative information as well as procedural learning. This study
      was conducted to examine the importance of sleep, especially the effects of
      midday naps, on motor sequence and visuomotor adaptation learning. Thirty-five
      (27 females) healthy, young adults aged between 18 and 30years of age
      participated in the current study. Addressing potential differences in explicit
      sequence and motor adaptation learning participants were asked to learn both, a
      nine-element explicit sequence and a motor adaptation task, in a crossover
      fashion on two consecutive days. Both tasks were performed with their non
      dominant left hand. Prior to learning, each participant was randomized to one of
      three interventions; (1) power nap: 10-20min sleep, (2) long nap: 50-80min sleep
      or (3) a 45-min wake-condition. Performance of the motor learning task took place
      prior to and after a midday rest period, as well as after a night of sleep. Both
      sleep conditions were dominated by Stage N2 sleep with embedded sleep spindles,
      which have been described to be associated with enhancement of motor performance.
      Significant performance changes were observed in both tasks across all
      interventions (sleep and wake) confirming that learning took place. In the
      present setup, the magnitude of motor learning was not sleep-dependent in young
      adults - no differences between the intervention groups (short nap, long nap, no
      nap) could be found. The effect of the following night of sleep was not
      influenced by the previous midday rest or sleep period. This finding may be
      related to the selectiveness of the human brain enhancing especially memory being
      thought of as important in the future. Previous findings on motor learning
      enhancing effects of sleep, especially of daytime sleep, are challenged.

PMID- 27021018
TI  - Characterization of melanocortin receptors from stingray Dasyatis akajei, a
      cartilaginous fish.
AB  - Melanocortin (MC) systems are composed of MC peptides such as adrenocorticotropic
      hormone (ACTH), several molecular forms of melanocyte-stimulating hormones (MSHs)
      and MC receptors (MCRs). Here we demonstrated that the cartilaginous fish,
      Dasyatis akajei (stingray) expresses five subtypes of MCR genes-mc1r to mc5r-as
      in the case of teleost and tetrapod species. This is the first evidence showing
      the presence of the full repertoire of melanocortin receptors in a single of
      cartilaginous fish. Expression of respective stingray mcr cDNAs in Chinese
      hamster ovary cells revealed that Des-acetyl-alpha-MSH exhibited cAMP-producing
      activity indistinguishable to ACTH(1-24) on MC1R and MC2R, while the activity of
      Des-acetyl-alpha-MSH on MC3R, MC4R, and MC5R were similar to or slightly greater
      than that of ACTH(1-24). Notably, in contrast to the other vertebrates, MC2R did
      not require coexpression with a melanocortin receptor-2 accessory protein 1
      (mrap1) cDNA for functional expression. One of the roles of MC system resides in
      regulation of the pituitary-interrenal (PI) axis-a homologue of tetrapod
      pituitary-adrenal axis. In stingray, interrenal tissues were shown to express
      mc2r and mc5r as major MCR genes. These results established the presence of
      functional PI axis in stingray at the level of receptor molecule. While MC2R
      participates in adrenal functions together with MRAP1 in tetrapod species, the
      fact that sensitivity of MC5R to Des-acetyl-alpha-MSH and ACTH(1-24) were two
      order of magnitude higher than MC2R without coexpression with MRAP1 suggested
      that MC5R could play a more important role than MC2R to transmit signals conveyed
      by ACTH and MSHs if MRAP1 is really absent in the stingray.

PMID- 27021019
TI  - Human Glutathione S-Transferase Enzyme Gene Polymorphisms and Their Association
      With Neurocysticercosis.
AB  - Neurocysticercosis (NCC), caused by cysticerci of Taenia solium is the most
      common helminthic infection of the central nervous system. Some individuals
      harboring different stages of cysticerci in the brain remain asymptomatic, while
      others with similar cysticerci lesions develop symptoms and the reasons remain
      largely unknown. Inflammatory response to antigens of dying parasite is said to
      be responsible for symptomatic disease. Reactive oxygen species (ROS) that are
      generated in inflammatory conditions can damage cellular macromolecules such as
      lipids, DNA, and proteins. The glutathione S-transferases (GSTs) are critical for
      the protection of cells from ROS. A total of 250 individuals were included in the
      study: symptomatic NCC = 75, asymptomatic NCC = 75, and healthy controls = 100.
      The individuals carrying the deletions of GSTM1 and GSTT1 were at risk for NCC
      (OR = 2.99, 95 %CI = 1.31-6.82, p = 0.0073 and OR = 1.94, 95 %CI = 0.98-3.82, p =
      0.0550 respectively). Further, the individuals with these deletions were more
      likely to develop symptomatic disease (OR = 5.08, 95 % CI = 2.12-12.18, p =
      0.0001 for GSTM1 and OR = 3.25, 95 %CI = 1.55-6.82, p = 0.0018 for GSTT1).
      Genetic variants of GSTM3 and GSTP1 were not associated with NCC. The total GST
      activity and levels of GSTM1, GSTT1, and GSTM3 were significantly higher in
      asymptomatic subjects than in symptomatic and healthy controls. Lower GST
      activity was observed in individuals with GSTM1 and GSTT1 deletions. The present
      study suggests that the individuals with GSTM1 and GSTT1 deletions are at higher
      risk to develop symptomatic disease. The higher GST activity and levels of GSTM1,
      GSTT1, and GSTM3 are likely to play role in maintaining asymptomatic condition.

PMID- 27021020
TI  - RAS Promotes Proliferation and Resistances to Apoptosis in Meningioma.
AB  - In this study, we investigated the influence of elevated RAS expression on the
      growth of meningioma in vivo and in vitro. The IOMM-LEE cells, representing a
      cell line derived from malignant meningioma, were divided into blank control
      group (cells without any drug treatment), negative control group (cells treated
      with an equal volume of normal saline to replace drug), and farnesyl
      thiosalicylic acid (FTS)-treated group (cells treated with FTS). Methyl-thiazole
      tetrazolium bromide (MTT) assay and flow cytometer (with cells after FTS (75
      MUmol/L) treatment for 48 h) were utilized to determine the proliferation and
      apoptosis, respectively, of IOMM-LEE cells after RAS inhibition. Western blot
      analysis was used for semi-quantitative analysis of p-ERK and p-AKT levels.
      Animal model of human meningioma was established with sub-renal capsule
      transplantation, and mice were divided into two groups: experimental group (50
      mg/kg group, 75 mg/kg group, and 100 mg/kg, hypodermic injection with FTS) and
      control group. Proliferating cell nuclear antigen (PCNA) was detected by
      immunohistochemistry (IHC). Western blot analysis was used for detecting ERK and
      AKT signal pathway. The proliferation of IOMM-LEE cells decreased dramatically
      and apoptosis rate increased significantly in FTS-treated group compared to blank
      control group and negative control group (all P < 0.05). At FTS concentration of
      75 MUmol/L, the apoptosis rate of IOMM-LEE cells reduced significantly over time
      (P < 0.05). Cell cycle analysis showed that IOMM-LEE cells exhibited G1-arrest in
      the FTS-treated group, compared to no cell-cycle arrest in blank control group
      and the negative control group (P < 0.05). Further, significantly decreased ERK
      and AKT phosphorylation levels were detected in IOMM-Lee cells after FTS (75
      MUmol/L) treatment for 48 h, compared to blank control group and negative control
      group (P < 0.05). The results in vivo experiments showed that after FTS
      treatment, tumor volume, PCNA LI, and the levels of p-ERK and p-Akt decreased
      significantly in 75 mg/kg group and 100 mg/kg group when compared with the
      control group and 50 mg/kg group (all P < 0.05). Our findings provide strong
      evidence that RAS protein is highly expressed in meningioma cells, and the RAS
      activity is inhibited by downregulating ERK and AKT signal pathway, which may
      further inhibit the growth of meningioma.

PMID- 27021021
TI  - The Protective Role of Selenium on Scopolamine-Induced Memory Impairment,
      Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1
      Channels.
AB  - Inhibition of Ca2+ entry into the hippocampus and dorsal root ganglion (DRG)
      through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is
      the current standard of care in neuronal diseases such as Alzheimer's disease,
      dementia, and peripheral pain. Oxidative stress activates Ca2+-permeable TRPM2
      and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and
      TRPV1 channel antagonist in the hippocampus and DRG. In this study, we
      investigated the neuroprotective properties of Se in primary hippocampal and DRG
      neuron cultures of aged rats when given alone or in combination with scopolamine
      (SCOP). Thirty-two aged (18-24 months old) rats were divided into four groups.
      The first and second groups received a placebo and SCOP (1 mg/kg/day),
      respectively. The third and fourth groups received intraperitoneal Se (1.5 mg/kg/
      over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were
      stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel
      agonist (cumene hydroperoxide). We found that Se was fully effective in reversing
      SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working
      memory and reference memory. In addition, Se completely reduced SCOP-induced
      oxidative toxicity by modulating lipid peroxidation, reducing glutathione and
      glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP
      ribose) polymerase activity, intracellular free Ca2+ concentrations, apoptosis,
      and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the
      hippocampus. In conclusion, the current study reports on the cellular level for
      SCOP and Se on the different endocytotoxic cascades for the first time. Notably,
      the research indicates that Se can result in remarkable neuroprotective and
      memory impairment effects in the hippocampal neurons of rats. Graphical abstract
      Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP)
      induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and
      TRPV1 channels in the hippocampus neurons of aged rats. The TRPM2 channel is
      activated by ADP-ribose and oxidative stress, although it is inhibited by ACA.
      The TRPV1 channel is activated by oxidative stress and capsaicin, and it is
      blocked by capsazepine (CPZ). The beta-amyloid plaque induces oxidative stress in
      hippocampus. SCOP can result in augmented ROS release in hippocampal neurons,
      leading to Ca2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were
      reported to accumulate Ca2+ provided that intracellular Ca2+ rises, thereby
      leading to the depolarization of mitochondrial membranes and release of apoptosis
      inducing factors such as caspase 3 and caspase 9. Se reduced TRPM2 and TRPV1
      channel activation through the modulation of aging oxidative reactions and Se
      dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

PMID- 27021022
TI  - Altered Long Noncoding RNA Expression Precedes the Course of Parkinson's Disease
      a Preliminary Report.
AB  - Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder that
      affects approximately seven million patients worldwide. Despite intensive
      research, the molecular mechanisms initiating and promoting PD are still unknown.
      However, it is assumed that environmental factors trigger PD. Recent research
      demonstrated that long noncoding RNAs (lncRNA) interfere in transcriptional and
      translational processes modulating gene expression reflecting environmental
      influences. Nevertheless, there is no systematic analysis available that
      investigates the impact of lncRNAs on PD. In the current study, we performed a
      comprehensive analysis on expression levels of 90 well-annotated lncRNAs in 30
      brain specimens deriving from 20 PD patients and 10 controls as a preliminary
      report on the significance of lncRNAs in PD. Expression profiling of lncRNAs
      revealed that five lncRNAs are significantly differentially expressed in PD.
      While H19 upstream conserved 1 and 2 is significantly downregulated in PD,
      lincRNA-p21, Malat1, SNHG1, and TncRNA are significantly upregulated. An analysis
      on expression levels and PD stages revealed that the identified dysregulated
      lncRNA are altered already in early disease stage and that they precede the
      course of PD. In summary, this is the first comprehensive analysis on lncRNAs in
      PD revealing significantly altered lncRNAs. Additionally, we found that lncRNA
      dysregulations precede the course of the disease. Thus, the five newly identified
      lncRNAs may serve as potential new biomarkers appropriate even in early PD. They
      may be used in monitoring disease progression and they may serve as potential new
      targets for novel therapeutic approaches.

PMID- 27021023
TI  - Genetic Variants of Microtubule Actin Cross-linking Factor 1 (MACF1) Confer Risk
      for Parkinson's Disease.
AB  - The cytoskeleton not only provides structure, it is an active component of cell
      function, and in several neurodegenerative disorders, there is evidence of
      cytoskeletal collapse. Cytoskeletal proteins have been specifically implicated in
      the pathogenesis of Parkinson's disease (PD), where degeneration of dopaminergic
      (DA) neurons is the hallmark, but in which many factors may determine the
      resilience of DA neurons during aging and stress. Here we report that the human
      Microtubule Actin Cross-linking Factor 1 gene (MACF1), a downstream target of PD
      biochemical pathways, was significantly associated with PD in 713 nuclear
      families. A significant allelic association between PD and rs12118033, with P =
      0.0098, was observed, and a P < 0.03 was observed in the association analysis by
      both a trend test and an allelic test. We further observed that it is the MACF1b
      isoform, not the MACF1a isoform, which is expressed in DA neurons from six human
      postmortem brains. In a Caenorhabditis elegans system, used to explore the effect
      of altered MACF1b on neurons, knockdown or knockout of the MACF1b orthologue vab
      10 resulted in the selective loss of DA neurons, which validated MACF1's risk
      candidacy in PD. These findings strongly suggest that MACF1b may contribute to
      the genetic etiology and mechanistic causation of PD.

PMID- 27021024
TI  - Ginsenoside Reduces Cognitive Impairment During Chronic Cerebral Hypoperfusion
      Through Brain-Derived Neurotrophic Factor Regulated by Epigenetic Modulation.
AB  - Increased expression of brain-derived neurotrophic factor (BDNF) has been
      associated with memory-enhancing and neuroprotective properties of some drugs
      under chronic cerebral hypoperfusion (CCH) condition. Ginsenoside Rd (GSRd), one
      of the main active ingredients in Panax ginseng, is widely used for brain
      protection. However, it is poorly understood whether epigenetic mechanisms
      implied in the BDNF modulation after GSRd treatment for CCH remain elusive. Here,
      we investigated the neuroprotective effects of GSRd and the involved mechanisms.
      We demonstrated that GSRd administration ameliorated CCH-induced impairment of
      learning and memory behaviors, evidenced by decreased escape latency and
      increased number of crossing the platform in Morris water maze test. This
      improvement was associated with promoted neuron survival and increased BDNF
      expression in the hippocampus and prefrontal cortex of CCH mice. GSRd improved
      neuron survival and decreased neuron apoptosis and the level of caspase-3 under
      oxygen-glucose deprivation/reoxygenation (OGD/R) by upregulation of BDNF as well
      as in vitro. The levels of acetylated histone H3 (Ac-H3) and histone deacetylase
      (histone deacetylase 2 (HDAC2)) were altered under OGD/R in a time-dependent
      manner, and GSRd reestablished the balance between Ac-H3 and HDAC2 which resulted
      in upregulation of BDNF and increased neuron survival. MS-275, an inhibitor of
      class I HDACs, abolished the levels of Ac-H3 at the bdnf promoters and enhanced
      upregulation of BDNF after GSRd administration, suggesting a synergistic effect
      between GSRd and MS-275. All the data suggested that GSRd provided
      neuroprotection by epigenetic modulation which accounted for the regulation of
      BDNF in CCH mice.

PMID- 27021025
TI  - Effect of DSPE-PEG on compound action potential, injury potential and ion
      concentration following compression in ex vivo spinal cord.
AB  - It has been shown that polyethylene glycol (PEG) can reseal membrane disruption
      on the spinal cord, but only high concentrations of PEG have been shown to have
      this effect. Therefore, the effect of PEG is somewhat limited, and it is
      necessary to investigate a new approach to repair spinal cord injury. This study
      assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N
      [methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological
      function and attenuate the injury-induced influx of extracellular ions in ex vivo
      spinal cord injury. Isolated spinal cords were subjected to compression injury
      and treated with PEG or DSPE-PEG immediately after injury. The compound action
      potential (CAP) was recorded before and after injury to assess the functional
      recovery. Furthermore, injury potential, the difference in gap potentials before
      and after compression, and the concentration of intracellular ions were used to
      evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the
      injury potential and ion concentration of the untreated, PEG and DSPE-PEG group,
      without significant difference among them, are remarkably higher than those of
      the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated
      spinal cords was significantly greater than that of the untreated spinal cords.
      The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same,
      but the concentration of DSPE-PEG used was much lower than the concentration of
      PEG. These results suggest that instant application of DSPE-PEG could effectively
      repair functional disturbance in SCI at a much lower concentration than PEG.

PMID- 27021026
TI  - Expression and function of calcitonin gene-related peptide (CGRP) receptors in
      trigeminal ganglia of R192Q Cacna1a knock-in mice.
AB  - Migraine is a neurovascular brain disorder suggested to be due to dysfunction of
      the trigeminovascular system with sensitization of trigeminal ganglion (TG)
      nociceptors. Since the neuropeptide calcitonin gene-related peptide (CGRP) has
      been established as a key player in the pathogenesis of migraine, CGRP receptor
      antagonists have been considered useful compounds to block headache originating
      from hyperactivation of such TG neurons. Whereas there is some information on the
      expression of CGRP receptors in postmortem human tissue, data are lacking for
      migraineurs suffering from common or genetic migraine. To help to clarify these
      issues it is very useful to study a transgenic knock-in (KI) mouse model of
      hemiplegic migraine expressing a R192Q missense mutation in the alpha1 subunit of
      CaV2.1 calcium channels previously found in patients with familial hemiplegic
      migraine type-1 (FHM-1). The aim of the present study, therefore, was to compare
      CGRP receptor expression and function in wildtype (WT) versus KI mouse TG. The
      principal components of the CGRP receptor, namely the CLR and RAMP-1 proteins,
      were similarly expressed in WT and KI TG neurons (in situ or in culture) and
      responded to exogenous CGRP with a strong rise in cAMP concentration. Hence, the
      previously reported phenotype of sensitization of KI TG neurons is not due to up
      regulation of CGRP receptors but is likely caused by a constitutively larger
      release of CGRP. This observation implies that, in FHM-1 TG, normal TG sensory
      neuron signaling can be restored once the extracellular concentration of CGRP
      returns to control level with targeted treatment.

PMID- 27021027
TI  - Dearomatization of Electron-Deficient Nitrogen Heterocycles via Cobalt-Catalyzed
      Asymmetric Cyclopropanation.
AB  - The dearomatization of a series of electron-deficient nitrogen heterocycles has
      been achieved through a cobalt-catalyzed asymmetric cyclopropanation reaction.
      This reaction proceeds with high levels of enantio- and diastereoselectivity to
      afford unique cyclopropanes that can be further functionalized to provide complex
      heterocyclic building blocks. 

PMID- 27021029
TI  - Development and Evaluation of a Three-Dimensional Multistation Cardiovascular
      Simulator.
AB  - BACKGROUND: To facilitate deliberate practice, we developed and evaluated a three
      dimensional multistation cardiovascular simulator with low-fidelity, anatomically
      correct materials. METHODS: Surgical educators and senior fellows at several
      national institutions who are a part of the Thoracic Education Cooperative Group
      completed expert validation surveys that feature a self-report rating scale,
      ranging from 0 (don't know) to 4 (highly realistic, no changes needed), and a
      global recommendation rating scale, ranging from 0 to 3. To analyze the survey
      results, we used paired Student t tests and a many-facet Rasch model. RESULTS: We
      analyzed the results of 18 expert validation surveys (completed by 9 senior
      fellows and by 9 staff surgeons). The overall realism-of-experience rating for
      the simulator was 3.23 (of 4), suggesting adequate realism with room remaining
      for improvement. Senior fellows rated the aortic graft replacement station and
      overall physical attributes more favorably than staff. Staff surgeons favored the
      simulator for realism of the mitral valve annuloplasty station and the
      cannulation station and for its use as a training tool. The overall global
      recommendation rating for the simulator was 2.38 (of 3), suggesting that the
      simulator can be considered for use in cardiovascular surgery training programs
      with minor improvements. CONCLUSIONS: This three-dimensional multistation
      cardiovascular simulator has adequate realism and can be considered for use in
      cardiovascular training programs. Platforms such as this may facilitate
      deliberate home practice and reinforcement of technical skills.

PMID- 27021030
TI  - Augmentation of the Lesser Curvature With an Autologous Vascular Patch in Complex
      Aortic Coarctation and Interruption.
AB  - BACKGROUND: Reconstruction of the aortic arch in patients with complex aortic
      coarctation or interruption continues to be a challenge because of early left
      main bronchial compression or recoarctation and late Gothic arch formation. We
      propose a modified arch reconstruction technique augmenting the lesser curvature
      with an autologous vascular patch, which can relieve tension on the anastomosis
      without a prosthetic material. METHODS: We retrospectively reviewed 33 patients
      with coarctation and arch hypoplasia (n = 31) or arch interruption (n = 2) who
      underwent arch reconstruction with an autologous vascular patch from 2007 to
      2012. Median age at the operation was 17 days (range, 5 to 200 days). Median body
      weight was 3.7 kg (range, 2.3 to 7.0 kg). Cardiopulmonary bypass was used for all
      operations. Median antegrade selective cerebral perfusion time was 35 minutes
      (range, 23 to 59 minutes). Combined intracardiac anomalies in 29 patients (88%)
      were corrected simultaneously. The reconstructed arch was supplemented in the
      lesser curvature with an autologous vascular patch that was harvested from aortic
      isthmus (n = 25), pulmonary artery (n = 4), left subclavian artery (n = 2),
      aberrant right subclavian artery (n = 1), or distal arch (n = 1). RESULTS: One
      patient (3%) died of acute respiratory distress syndrome. All survivors were
      discharged at 15 days (range, 7 to 58 days) postoperatively without neurologic
      complications or bronchial obstructions. Median follow-up was 24.8 months (range,
      0.2 to 48.5 months). No recoarctation was observed during follow-up, and no
      patient needed reoperation. CONCLUSIONS: Augmenting the lesser curvature with an
      autologous vascular patch during arch reconstruction resulted in excellent
      midterm outcomes. Not only can a more natural shape of arch and less tension on
      the anastomosis be obtained, but complications, such as left main bronchial
      obstruction or recoarctation, can also be minimized. Long-term follow-up is
      needed to evaluate late development of recoarctation, hypertension, or aneurysm
      formation.

PMID- 27021031
TI  - Reexploration for Bleeding and Its Association With Mortality After Cardiac
      Surgery.
AB  - BACKGROUND: Excessive bleeding after cardiac surgical procedures sometimes
      necessitates reexploration. This study described the associations between
      reexploration for bleeding and morbidity and mortality after cardiac surgical
      procedures. In addition, independent predictors of reexploration were identified.
      METHODS: This retrospective observational study based on prospectively registered
      data included 5,392 consecutive cardiac surgical operations performed from 2009
      through 2013. Reexplorations for bleeding within 24 hours of surgical procedures
      and perioperative morbidity and mortality (30-day, 90-day, and from 90 days until
      the end of follow-up) were registered. Factors independently associated with
      mortality, morbidity, and reexploration were identified with multivariable
      logistic or Cox regression models. Mean follow-up time was 2.4 years (range 0 to
      5 years). RESULTS: In this study, 320 patients (6.0%) underwent surgical
      reexploration. These patients had higher unadjusted mortality at 30 days, 90
      days, and more than 90 days (all p < 0.0001). The increased risk remained
      statistically significant after adjustment for other risk factors at 90 days
      (odds ratio [OR]: 1.82; 95% confidence interval [CI]: 1.13 to 2.93; p = 0.013)
      and at more than 90 days (hazard ratio: 1.72; 95% CI: 1.14 to 2.61; p = 0.010).
      Reexploration was, after adjustment, independently associated with prolonged stay
      in the intensive care unit (>24 hours), perioperative stroke, perioperative renal
      injury, need for dialysis postoperatively, prolonged mechanical ventilation (>72
      hours), and postoperative mechanical circulation support. Independent risk
      factors for reexploration were low body mass index, high EuroSCORE, low
      preoperative fibrinogen plasma concentration, long extracorporeal circulation
      time, combined valve and coronary artery bypass operations, and dual antiplatelet
      therapy less than 5 days preoperatively. CONCLUSIONS: Excessive bleeding leading
      to reexploration is associated with a twofold increased early postoperative
      mortality rate. Reexploration for bleeding is also associated with mortality
      beyond 90 days after operation.

PMID- 27021032
TI  - Fibrinogen Levels After Cardiac Surgical Procedures: Association With
      Postoperative Bleeding, Trigger Values, and Target Values.
AB  - BACKGROUND: Low fibrinogen levels immediately after cardiac surgical procedures
      have been associated with postoperative bleeding and transfusions. However, no
      sound data on the adequate trigger values for fibrinogen supplementation and
      target values for fibrinogen concentration exist. METHODS: This retrospective
      study examined prospectively collected data, including data on 2,800 adult
      patients undergoing cardiac operations. Standard coagulation parameters at the
      arrival in the intensive care unit were retrieved, inclusive of fibrinogen
      levels. Postoperative bleeding was assessed based on the chest drain output
      (mL/12 h). Severe bleeding (SB) was defined as chest drain output greater than
      1,000 mL/12 h. RESULTS: Postoperative blood loss was associated with low values
      of fibrinogen and platelet count, as well as with a prolonged activated partial
      thromboplastin time and international normalized ratio. At multivariable
      analysis, fibrinogen levels lower than 220 mg/dL remained independently
      associated with SB (odds ratio: 2.25; 95% confidence interval: 1.54 to 3.28). A
      cutoff value of 115 mg/dL yielded a positive predictive value for SB of 50% and
      may be proposed as a trigger value for fibrinogen supplementation, with a target
      value of 280 mg/dL (98% negative predictive value for SB). In actively bleeding
      patients, these values are increased to 215 and 375 mg/dL, respectively.
      CONCLUSIONS: These data confirm the independent role of fibrinogen levels as
      determinants of SB after cardiac surgical procedures and suggest adequate cutoff
      values and fibrinogen concentrate doses to prevent or treat SB. However, the
      identified trigger and target values should be confirmed in prospective series of
      patients undergoing fibrinogen supplementation.

PMID- 27021033
TI  - Variation in Pulmonary Resection Practices Between The Society of Thoracic
      Surgeons and the European Society of Thoracic Surgeons General Thoracic Surgery
      Databases.
AB  - BACKGROUND: Clinical guidelines are created to reduce variation in care
      practices, with the goal of improving patient outcomes. There is currently no
      international consensus on best practices for pulmonary resection. Our aim was to
      evaluate variation in treatment patterns and outcomes for pulmonary resection by
      comparing The Society of Thoracic Surgeons (STS) and the European Society of
      Thoracic Surgery (ESTS) general thoracic surgery databases (GTSDs). METHODS: An
      international collaboration was established between the STS and ESTS GTSD task
      forces. Patients who underwent pulmonary resection between 2010 and 2013 were
      identified from the 2 databases. Data on patient demographics, disease
      characteristics, treatment strategies, morbidity, and mortality were compared.
      RESULTS: There were 78,212 lung resections captured in the STS (n = 47,539) and
      ESTS databases (n = 30,673). Patients from the STS database were more likely to
      be of the female sex, have no pathologic N2 disease, have had previous
      cardiothoracic operations, and have received preoperative thoracic irradiation
      compared with patients from the ESTS database. In addition, patients from the STS
      database were more likely to have undergone a thoracoscopic operation and have
      received a sublobar resection. Although there was an increased risk of
      reintubation, atrial arrhythmias, and return to the operating room in the STS
      patients, the mean hospital length of stay was shorter than in patients from the
      ESTS database, regardless of operation performed. Thirty-day mortality was higher
      in the STS patients for wedge resection (p < 0.001) but lower for lobectomy (p <
      0.001) and pneumonectomy (p < 0.001) compared with the ESTS patients.
      CONCLUSIONS: Differences exists in patient population, procedures performed, and
      outcomes for pulmonary resections between the STS and ESTS databases, suggesting
      an opportunity for quality improvement initiatives.

PMID- 27021034
TI  - Regional Left Ventricular Reverse Remodeling After Myectomy in Hypertrophic
      Cardiomyopathy.
AB  - BACKGROUND: Surgical extended septal myectomy is appropriate treatment for
      obstructive hypertrophic cardiomyopathy (HCM) with refractory symptoms. Using 3
      layer speckle tracking imaging, we aimed to evaluate the effects of myectomy on
      left ventricular (LV) regions and the potential factors associated with LV
      reverse remodeling. METHODS: In 71 patients (mean age, 41.0 +/- 15.0 years)
      undergoing septal myectomy, 3-layer speckle tracking was performed before
      myectomy and latest review. We evaluated the myectomy site (target anteroseptum)
      and LV free wall longitudinal strain (LS) and circumferential strain (CS) in
      endocardial, midmyocardial, and epicardial layers. The thickness of each free
      wall segment was calculated and totaled for the free wall thickness score.
      RESULTS: Compared with before myectomy, LS increased; however, CS decreased at
      the myectomy site after myectomy. For the free wall, LS and CS improved in all 3
      layers after the procedure (all p < 0.05). Factors independently associated with
      latest-review free wall strain were free wall thickness score (LS, beta = -0.150;
      p < 0.001; CS, beta = -0.090; p < 0.001), age (LS, beta = 0.118; p < 0.001), and
      DeltaLV outflow tract gradient (CS, beta = 0.039; p = 0.002). Factors
      independently associated with myectomy site strain were resected thickness (LS,
      beta = -0.439; p = 0.001; CS, beta = -0.736; p = 0.001), and age (LS, beta =
      0.178; p < 0.001). CONCLUSIONS: Sufficient relief of obstruction and lower
      resected thickness in the target anteroseptum lead to more favorable remodeling.
      Free wall thickness score and age are important factors associated with reverse
      remodeling.

PMID- 27021035
TI  - Characterizing the Operative Experience of Cardiac Surgical Trainees: What Are
      Residents Really Doing in the Operating Room?
AB  - BACKGROUND: The present study aimed to describe and compare the operative
      experience of cardiothoracic surgical residents for basic and advanced cardiac
      surgical procedures. METHODS: Data were obtained from the 2015 Thoracic Surgery
      Directors Association Survey administered to all thoracic surgical residents
      taking the yearly In-Service Training Examination (n = 356). Residents were asked
      whether they routinely served as the operative surgeon on various cardiac
      operations and operative tasks. Results were stratified by postgraduate year
      (PGY), residency type, and primary career interest. RESULTS: The survey response
      rate was 100%. Considering all training pathways, only 2 of 13 cardiac operations
      surveyed were routinely performed by graduating chief residents as the operative
      surgeon: coronary artery bypass grafting (CABG; 92%) and aortic valve replacement
      (AVR; 88%). Off-pump CABG, minimally invasive mitral valve operation, and
      transcatheter aortic interventions were infrequently (<30% of the time) performed
      by graduating residents as the operative surgeon. These results were similar when
      residents with a career interest in general thoracic surgery were excluded from
      the analysis. For the operative progression of integrated 6-year (I-6) residents,
      most began to routinely cannulate for cardiopulmonary bypass, perform proximal
      coronary anastomoses, and harvest the mammary artery during PGY3. The majority
      (>50%) of I-6 residents performed CABG as the operative surgeon by PGY4.
      CONCLUSIONS: There is pronounced heterogeneity in the cardiac operative
      experience of cardiothoracic surgical residents in the United States, with only
      CABG and AVR routinely performed by graduating residents as the operative
      surgeon. This heterogeneity may lead to insufficient training in certain
      procedures for many graduates.

PMID- 27021037
TI  - Congenital Herpes Simplex Virus in the Newborn: A Diagnostic Dilemma.
AB  - Although congenital herpes simplex virus (HSV) infection is rare, it is
      associated with severe morbidity. We report a 36-week gestational age infant who
      presented with atypical skin lesions, presumably mitigated by exposure to
      maternal antiviral suppressive therapy. The initial absence of typical herpetic
      vesicles and lack of viral detection in skin lesions delayed the correct
      diagnosis, highlighting the importance of differentiating HSV from other neonatal
      rashes. 

PMID- 27021036
TI  - Colonization With Antimicrobial-Resistant Gram-Negative Bacilli at Neonatal
      Intensive Care Unit Discharge.
AB  - Background: The epidemiology of the colonization of infants with antimicrobial
      resistant Gram-negative bacilli (GNB) at discharge from the neonatal intensive
      care unit (NICU) is not well understood. Methods: A multicenter study in which
      rectal surveillance samples for culture were obtained at NICU discharge from
      infants hospitalized >=14 days was performed. Factors associated with
      colonization with GNB resistant to gentamicin, third/fourth-generation
      cephalosporin agents, or carbapenem agents were assessed by using a fixed-effects
      model. Results: Of these infants, 9% (119 of 1320) were colonized with >=1
      antimicrobial-resistant GNB. Prolonged treatment (>=10 days) with meropenem or
      third/fourth-generation cephalosporin agents or treatment for >=5 days with a
      beta-lactam/beta-lactamase combination agent were associated with an increased
      risk of colonization with GNB resistant to gentamicin. Surgery and >=5 days of
      treatment with third/fourth-generation cephalosporin agents, a beta-lactam/beta
      lactamase combination agent, or metronidazole were associated with an increased
      risk of colonization with GNB resistant to third/fourth-generation cephalosporin
      agents. Female sex and prolonged treatment (>=10 days) with meropenem were
      associated with colonization with GNB resistant to carbapenem agents.
      Conclusions: Prolonged treatment with broad-spectrum antibiotics was associated
      with the colonization of infants with antimicrobial-resistant GNB within 7 days
      of NICU discharge. These findings suggest the potential for dissemination of
      resistant GNB from colonized infants to other NICUs, the community, or pediatric
      long-term care facilities. Antimicrobial stewardship efforts aimed at improving
      appropriate antibiotic use could have a beneficial effect on the emergence of
      antimicrobial-resistant GNB in the NICU population.

PMID- 27021038
TI  - Auditory Temporal Processing Deficits in Chronic Stroke: A Comparison of Brain
      Damage Lateralization Effect.
AB  - BACKGROUND: There have been a few reports about the effects of chronic stroke on
      auditory temporal processing abilities and no reports regarding the effects of
      brain damage lateralization on these abilities. Our study was performed on 2
      groups of chronic stroke patients to compare the effects of hemispheric
      lateralization of brain damage and of age on auditory temporal processing.
      METHODS: Seventy persons with normal hearing, including 25 normal controls, 25
      stroke patients with damage to the right brain, and 20 stroke patients with
      damage to the left brain, without aphasia and with an age range of 31-71 years
      were studied. A gap-in-noise (GIN) test and a duration pattern test (DPT) were
      conducted for each participant. RESULTS: Significant differences were found
      between the 3 groups for GIN threshold, overall GIN percent score, and DPT
      percent score in both ears (P <= .001). For all stroke patients, performance in
      both GIN and DPT was poorer in the ear contralateral to the damaged hemisphere,
      which was significant in DPT and in 2 measures of GIN (P <= .046). Advanced age
      had a negative relationship with temporal processing abilities for all 3 groups.
      CONCLUSIONS: In cases of confirmed left- or right-side stroke involving auditory
      cerebrum damage, poorer auditory temporal processing is associated with the ear
      contralateral to the damaged cerebral hemisphere. Replication of our results and
      the use of GIN and DPT tests for the early diagnosis of auditory processing
      deficits and for monitoring the effects of aural rehabilitation interventions are
      recommended.

PMID- 27021039
TI  - Intracranial Stenting as a Rescue Therapy in Patients with Stroke-in-Evolution.
AB  - BACKGROUND: The feasibility and efficacy of intracranial stenting were evaluated
      for patients with a stroke-in-evolution after the time window for thrombolysis.
      METHODS: Patients with symptomatic intracranial steno-occlusive disease with
      progressive or fluctuating symptoms were treated using intracranial stenting
      after the time window for hyperacute thrombolysis. RESULTS: Within the study
      period, we identified 10 patients (7 men, 62.5 +/- 11.3 years old) who were
      eligible for inclusion. The median onset-to-arrival time was 5.8 hours (range: .6
      144 hours), and the median onset-to-procedure time was 33 hours (range: 8-346
      hours). Only 1 patient previously received intravenous thrombolysis using
      alteplase. The symptomatic occlusive artery was the right middle cerebral artery,
      left middle cerebral artery, and basilar artery in 3, 1, and 6 patients,
      respectively. The median initial National Institutes of Health Stroke Scale
      (NIHSS) score was 4 (range: 0-6), and the median NIHSS score measured immediately
      before the procedure was 8 (range: 4-26). All but 1 patient underwent successful
      angioplasty and stenting using a Wingspan stent. Reocclusion of the stented
      artery occurred in 1 patient, and his neurological status deteriorated to coma. A
      favorable outcome (modified Rankin Scale <=2) at 3 months was noted in 7 patients
      (70%). CONCLUSION: Intracranial stenting could be considered an alternative
      strategy for treating patients with medically intractable stroke-in-evolution.

PMID- 27021040
TI  - Relative Mean Transit Time Predicts Subsequent Stroke in Symptomatic Carotid
      Occlusion.
AB  - BACKGROUND: Mean transit time (MTT) measurements to assess cerebral hemodynamics
      are easily obtained by computed tomography and magnetic resonance imaging. We
      reviewed hemodynamic and clinical outcome data from the St. Louis Carotid
      Occlusion Study to determine if increased MTT was associated with an increased
      risk of stroke in patients with symptomatic complete carotid artery occlusion.
      METHODS: Positron emission tomography (PET) studies of cerebral blood volume-to
      cerebral blood flow ratios were used to calculate MTTs. Mean ipsilateral (side of
      the occluded internal carotid artery)-to-contralateral ratios of MTTs in the
      middle cerebral artery territories were determined. MTT was tested as a predictor
      of stroke risk using Cox regression analysis. Receiver operating characteristic
      curves for stroke risk prediction were generated by varying the mean ispilateral
      to-contralateral MTT ratio to identify an optimal cutpoint. RESULTS: Increased
      MTT ratio was associated with an increased risk of ipsilateral stroke (P < .001).
      The maximum combination of sensitivity (.778) and specificity (.763) was obtained
      at a cutpoint ratio of 1.387 or higher. Subjects with a MTT ratio of 1.387 or
      higher had a 29.3% 2-year risk of ipsilateral stroke compared to 4.6% for those
      without (P < .001). CONCLUSIONS: PET relative MTT ratio identified patients with
      symptomatic complete internal artery occlusion who were at high risk for
      subsequent ipsilateral stroke. Confirmation using measurements of relative MTT
      from other imaging modalities in a patient cohort receiving contemporary medical
      management is needed.

PMID- 27021041
TI  - Low Ankle-Brachial Index is a Simple Physical Exam Sign Predicting Intracranial
      Atherosclerotic Stenosis in Ischemic Stroke Patients.
AB  - BACKGROUND: The investigation of ischemic stroke etiology is commonly limited to
      the heart and extracranial vessels. Nevertheless, the diagnosis of intracranial
      stenosis may carry important therapeutic implications. The aims of this study
      were to determine the prevalence and clinical predictors of intracranial
      atherosclerotic stenosis (ICAS) in a sample of patients with ischemic stroke.
      METHODS: Consecutive patients admitted to a university-based outpatient stroke
      clinic underwent CT angiography of the intracranial and extracranial brain
      vessels. Clinical, demographic, and laboratory characteristics were compared
      between patients with increasing levels of stenosis. Ankle-brachial index (ABI)
      was measured to quantify peripheral arterial disease, defined as an ABI less than
      or equal to .9. Multivariable ordinal logistic regression was constructed to
      predict increasing stenosis grades (none, 1%-49%-mild, 50%-69%-moderate, 70%-100%
      severe). RESULTS: We studied 106 subjects, mean age 62 +/- 15 years, 54% female.
      ICAS was present in 38 (36%) patients: 19 (50%) mild, 7 (18%) moderate, and 12
      (32%) severe. Of 74 patients where ABI was measured, low ABI was found more
      frequently with increasing ICAS severity (26%, 42%, 67%, and 89% of patients with
      none, mild, moderate, and severe ICAS, respectively). In univariable analysis,
      higher age, presence of diabetes, abdominal obesity, and low ABI correlated with
      increasing stenosis grades. In multivariable analysis, only low ABI remained
      independently associated with increasing stenosis grades. CONCLUSIONS: The ABI is
      independently associated with increasing severity of ICAS, making it a
      potentially useful triaging tool for more invasive test selection.

PMID- 27021043
TI  - Effectiveness of three pneumococcal conjugate vaccines to prevent invasive
      pneumococcal disease in Quebec, Canada.

PMID- 27021042
TI  - Intracranial Plaque Characterization in Patients with Acute Ischemic Stroke Using
      Pre- and Post-Contrast Three-Dimensional Magnetic Resonance Vessel Wall Imaging.
AB  - BACKGROUND: Magnetic resonance vessel wall imaging (VWI) techniques have been
      developed to assess atherosclerotic plaques in intracranial arteries, which are a
      cardinal cause of ischemic stroke. However, the clinical roles of plaque-related
      vulnerability and inflammation remain unclear. Hence, we evaluated plaque
      characteristics using VWI of the proximal middle cerebral artery (M1) in patients
      with acute ischemic stroke. METHODS: We prospectively examined 30 consecutive
      patients with acute noncardioembolic stroke in the M1 territory using pre
      /postcontrast T1-weighted (T1W) three-dimensional (3D) VWI with a 3-Tesla
      scanner. The contrast ratio (CR) and contrast enhancement of the plaques were
      measured bilaterally at M1. RESULTS: Plaques were identified in the bilateral M1s
      of all patients, and no substantial stenosis existed. The M1 plaque CRs
      ipsilateral to the infarct (46.7%-67.9%) were significantly higher than the
      plaque CRs on the contralateral side (34.3%-69.4%), particularly in patients with
      lacunar infarcts (P <.01). In contrast, the occurrence of plaque enhancement was
      not different between the ipsilateral (20.0%) and contralateral (16.7%) sides.
      Further, the CRs in the nonlacunar group were significantly higher than the CRs
      in the lacunar group (P <.05), whereas enhanced plaques tended to be more
      frequent in the nonlacunar group, but this difference was not significant (P =
      .09). CONCLUSIONS: T1W 3D-VWI revealed that the signal intensity of M1 plaques
      was significantly higher in the affected side and in nonlacunar-type infarcts of
      patients with acute stroke, suggesting that unstable plaques in the M1 can cause
      stroke events presumably due to atherothrombotic mechanisms.

PMID- 27021044
TI  - Single-Level Rigid Fixation Combined with Coflex: A Biomechanical Study.
AB  - BACKGROUND: The purpose of this biomechanical in vitro study was to compare the
      kinematics and intradiscal pressure achieved with 2 methods: L4-L5 pedicle screw
      rod fixation (PSRF) with an upper L3-L4 Coflex device and L4-L5 PSRF alone. The
      results were used to characterize the biomechanics of the topping-off operation
      with a Coflex device for the lumbar motion segment adjacent to single-level rigid
      fixation. MATERIAL/METHODS: Six human cadaveric spine specimens were
      biomechanically tested in vitro (6 males, 0 females). The 3-dimensional specimen
      motion in response to applied loads during flexibility tests was determined.
      Loads were applied along anatomic axes to induce flexion-extension, lateral
      bending, and axial rotation. All specimens were first studied with intact lumbar
      motion segments, then with L4-L5 PSRF alone, and finally with L4-L5 PSRF with an
      upper L3-L4 Coflex device. A non-paired comparison of the 3 configurations under
      3 different conditions was made. RESULTS: PSRF, with or without a Coflex device,
      significantly increased the range of motion (ROM) in the upper adjacent motion
      segments in all directions of loading. The intradiscal pressure (IDP) changed
      slightly. A correlation analysis showed that the ROM and IDP are significantly
      positively correlated. The application of the upper motion segment of the Coflex
      device provided greater stability in all directions of motion than did PSRF
      alone, particularly for extension (p<0.05), while use of a Coflex device did not
      significantly decrease the IDP compared with PSRF alone (p>0.05). CONCLUSIONS:
      These results suggest that L4-L5 PSRF with an L3-L4 Coflex device is more stable
      than L4-L5 PSRF alone. PSRF with an upper Coflex device is a promising
      alternative to PSRF alone. Based on these biomechanical tests, it might be
      considered a protective method to prevent adjacent segment degeneration (ASD),
      although some limitations with this in vitro study must be addressed in the
      future.

PMID- 27021045
TI  - Coffee Drinking and Risk of Lung Cancer-A Meta-Analysis.
AB  - BACKGROUND: Previous epidemiologic results on coffee consumption and lung cancer
      risk have not been consistent. Furthermore, not all studies have addressed the
      potential role of tobacco as a confounder in this association. A meta-analysis
      was conducted to assess the effect of coffee consumption on lung cancer risk
      independent of tobacco use. METHODS: A systematic review and a meta-analysis
      based on random effects models were performed using studies from the PubMed and
      EMBASE databases, and the references from the retrieved articles. Included were 8
      prospective cohorts and 13 case-control studies, which provided data for 19,892
      cases and 623,645 non-cases, timeframe 1986-2015. RESULTS: The meta-relative risk
      (RR) for coffee drinking, not controlling for tobacco smoking, was 1.09 [95%
      confidence interval (CI), 1.00-1.19], the reference group was never drinkers.
      There was significant heterogeneity among the study results (Q = 84.39, I2 =
      75.1%, Pheterogeneity < 0.001). Among non-smokers, coffee was not associated with
      lung cancer risk (RR, 0.92; 95% CI, 0.75-1.10), the reference group was never
      drinkers. The meta-RR for 1 cup per day increase, unadjusted for smoking, was
      1.04 (95% CI, 1.03-1.05); the corresponding RR for non-smokers was 0.95 (95% CI,
      0.83-1.09). CONCLUSIONS: The pooled estimates indicated that when the potential
      confounding effect from smoking is controlled for, coffee drinking does not
      appear to be a lung cancer risk factor. Further pooled analyses, with larger non
      smokers population size, are encouraged to confirm these results. IMPACT: This
      study illustrates that the association between coffee consumption and lung cancer
      can be confounded by tobacco smoking. Cancer Epidemiol Biomarkers Prev; 25(6);
      951-7. (c)2016 AACR.

PMID- 27021047
TI  - Enhanced ionic liquid mobility induced by confinement in 1D CNT membranes.
AB  - Water confined within carbon nanotubes (CNT) exhibits tremendous enhanced
      transport properties. Here, we extend this result to ionic liquids (IL) confined
      in vertically aligned CNT membranes. Under confinement, the IL self-diffusion
      coefficient is increased by a factor 3 compared to its bulk reference. This could
      lead to high power battery separators. 

PMID- 27021046
TI  - No Association between the Mitochondrial Genome and Prostate Cancer Risk: The
      Multiethnic Cohort.
AB  - BACKGROUND: Mitochondria are involved in many processes that are central to the
      life and death of a cell. Oxidative phosphorylation (OXPHOS), in particular, is
      known to be altered in carcinogenesis, leading to an increase in the production
      of reactive oxidative species and glycolysis, one of the hallmarks of cancer
      cells. Because of this, genetic variation in the mitochondrial genome, which
      encodes for part of the OXPHOS pathway, has been suggested to play a role in many
      cancers, including prostate cancer. METHODS: We comprehensively examined the role
      of the mitochondrial genome and prostate cancer risk in 4,086 prostate cancer
      cases and 3,698 controls from the Multiethnic Cohort (MEC), testing 350
      mitochondrial SNPs (mtSNPs) in five racial/ethnic populations-Africans, Asian
      Americans, Europeans, Latinos, and Native Hawaiians. Logistic regression was
      conducted to examine single mitochondrial SNP and haplogroup associations. The
      sequence kernel association test was conducted for gene and pathway analysis.
      RESULTS: Eleven mtSNPs and haplogroup N were nominally associated with overall
      prostate cancer risk at P < 0.05. The mitochondrial DNA-encoded OXPHOS pathway,
      complexes, and genes were not associated with prostate cancer risk. No
      significant associations were identified after multiple testing corrections (all
      FDR q > 0.20). CONCLUSIONS: The mitochondrial genome was not associated with
      prostate cancer risk in our study of 7,784 subjects from the MEC. IMPACT: Our
      comprehensive study does not support the role of the mitochondrial genome in the
      risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 1001-3. (c)2016
      AACR.

PMID- 27021048
TI  - [Role of the mTOR pathway in the central regulation of energy balance].
AB  - The pathway of the mammalian (or mechanistic) target of rapamycin kinase (mTOR)
      responds to different signals such as nutrients and hormones and regulates many
      cellular functions as the synthesis of proteins and lipids, mitochondrial
      activity and the organization of the cytoskeleton. At the cellular level, mTOR
      forms two distinct complexes: mTORC1 and mTORC2. This review intends to summarize
      the various recent advances on the role of these two protein complexes in the
      central regulation of energy balance. mTORC1 activity modulates energy balance
      and metabolic responses by regulating the activity of neuronal populations, such
      as those located in the arcuate nucleus of the hypothalamus. Recent studies have
      shown that activity of the hypothalamic mTORC1 pathway varies according to cell
      and stimulus types, and that this signaling cascade regulates food intake and
      body weight in response to nutrients, such as leucine, and hormones like leptin,
      ghrelin and triiodothyronine. On the other hand, mTORC2 seems to be involved in
      the regulation of neuronal morphology and synaptic activity. However, its
      function in the central regulation of the energy balance is less known.
      Dysregulation of mTORC1 and mTORC2 is described in obesity and type 2 diabetes.
      Therefore, a better understanding of the molecular mechanisms involved in the
      regulation of energy balance by mTOR may lead to the identification of new
      therapeutic targets for the treatment of these metabolic pathologies. 

PMID- 27021049
TI  - [Role of fatty acids in the nervous control of energy balance].
AB  - Fatty acid (FA)-sensitive neurons are present in the brain, especially the
      hypothalamus, and play a key role in the neural control of energy and glucose
      homeostasis including feeding behavior, insulin secretion and action.
      Subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are
      selectively either inhibited or activated by FA. Molecular effectors of these FA
      effects include ion channels such as chloride, potassium or calcium. In addition
      at least half of the FA responses in ventromedial hypothalamic neurons are
      mediated by interaction with FAT/CD36, a FA translocator/receptor that does not
      require intracellular metabolism to activate downstream signaling. Recently, an
      important role of lipoprotein lipase in FA sensing has also been demonstrated not
      only in hypothalamus, but also in the hippocampus and striatum. Finally, FA
      overload might impair neural control of energy homeostasis through enhanced
      ceramide synthesis and may contribute to obesity and/or type 2 diabetes
      pathogenesis in predisposed subjects. 

PMID- 27021050
TI  - [Adaptation to the availability of essential amino-acids: role of
      GCN2/eIF2alpha/ATF4 pathway].
AB  - In mammals, metabolic adaptations are required to overcome nutritional
      deprivation in amino-acids/proteins as well as episodes of malnutrition. GCN2
      protein kinase, which phosphorylates the alpha subunit of the translation
      initiation factor eIF2, is a sensor of amino-acid(s) deficiencies. On one hand,
      this review briefly describes the main features of amino-acid metabolism. On the
      other hand, it describes the role of GCN2 in regulating numerous physiological
      functions. 

PMID- 27021051
TI  - [Nutrient sensing by the gastro-intestinal nervous system and control of energy
      homeostasis].
AB  - The gastrointestinal nerves are crucial in the sensing of nutrients and hormones
      and its translation in terms of control of food intake. Major macronutrients like
      glucose and proteins are sensed by the extrinsic nerves located around the portal
      vein walls, which signal to the brain and account for the satiety phenomenon they
      promote. Glucose is sensed in the portal vein by neurons expressing the glucose
      receptor SGLT3, which activates the main regions of the brain involved in the
      control of food intake. Proteins indirectly act on food intake by inducing
      intestinal gluconeogenesis and its sensing by the portal glucose sensor. The
      mechanism involves a prior antagonism by peptides of the MU-opioid receptors
      present in the portal vein nervous system and a reflex arc with the brain
      inducing intestinal gluconeogenesis. In a comparable manner, short chain fatty
      acids produced from soluble fibers act via intestinal gluconeogenesis to exert
      anti-obesity and anti-diabetic effects. In the case of propionate, the mechanism
      involves a prior activation of the free fatty acid receptor FFAR3 present in the
      portal nerves and a reflex arc initiating intestinal gluconeogenesis. 

PMID- 27021052
TI  - [From dualism to multiplicity: seeing BCL-2 family proteins and cell death with
      new eyes].
AB  - The concept of cell death has many links to the concept of death itself, defined
      as the opposite of life. Achievements obtained through research on apoptosis have
      apparently allowed us to transcend this Manichean view. Death is no longer
      outside, but rather inside living systems, as a constitutive force at work within
      the living matter. Whereas the death of cells can be positive and breed
      "creation" (e.g. during morphogenesis), its dysregulation can also cause or
      contribute to fatal diseases including cancer. It is tempting to apply this
      biological discourse to illuminate the relations between life and death, taken in
      general terms, but does this generalization actually hold? Is this discourse not
      essentially a metaphor? If cell death is considered as a vital aspect of various
      biological processes, then are we not faced with some vitalistic conception of
      death? Are there one or more meanings to the word "death"? Does the power to self
      destruct act in opposition to other key features of living entities, or rather in
      juxtaposition to them? In this article, we first describe how the field of cell
      death has been developed on the basis of perceived and built dichotomies,
      mirroring the original opposition between life and death. We detail the
      limitations of the current paradigm of apoptosis regulation by BCL-2 family
      proteins, which nicely illustrate the problem of binary thinking in biology.
      Last, we try to show a way out of this dualistic matrix, by drawing on the
      notions of multiplicity, complexity, diversity, evolution and contingency. 

PMID- 27021054
TI  - P-Channel InGaN/GaN heterostructure metal-oxide-semiconductor field effect
      transistor based on polarization-induced two-dimensional hole gas.
AB  - The concept of p-channel InGaN/GaN heterostructure field effect transistor (FET)
      using a two-dimensional hole gas (2DHG) induced by polarization effect is
      demonstrated. The existence of 2DHG near the lower interface of InGaN/GaN
      heterostructure is verified by theoretical simulation and capacitance-voltage
      profiling. The metal-oxide-semiconductor FET (MOSFET) with Al2O3 gate dielectric
      shows a drain-source current density of 0.51 mA/mm at the gate voltage of -2 V
      and drain bias of -15 V, an ON/OFF ratio of two orders of magnitude and effective
      hole mobility of 10 cm(2)/Vs at room temperature. The normal operation of MOSFET
      without freeze-out at 8 K further proves that the p-channel behavior is
      originated from the polarization-induced 2DHG.

PMID- 27021053
TI  - Unravelling Linkages between Plant Community Composition and the Pathogen
      Suppressive Potential of Soils.
AB  - Plant diseases cause dramatic yield losses worldwide. Current disease control
      practices can be deleterious for the environment and human health, calling for
      alternative and sustainable management regimes. Soils harbour microorganisms that
      can efficiently suppress pathogens. Uncovering mediators driving their
      functioning in the field still remains challenging, but represents an essential
      step in order to develop strategies for increased soil health. We set up plant
      communities of varying richness to experimentally test the potential of soils
      differing in plant community history to suppress the pathogen Rhizoctonia solani.
      The results indicate that plant communities shape soil-disease suppression via
      changes in abiotic soil properties and the abundance of bacterial groups
      including species of the genera Actinomyces, Bacillus and Pseudomonas. Further,
      the results suggest that pairwise interactions between specific plant species
      strongly affect soil suppressiveness. Using structural equation modelling, we
      provide a pathway orientated framework showing how the complex interactions
      between plants, soil and microorganisms jointly shape soil suppressiveness. Our
      results stress the importance of plant community composition as a determinant of
      soil functioning, such as the disease suppressive potential of soils. 

PMID- 27021055
TI  - Is the evidence base of methylphenidate for children and adolescents with
      attention-deficit/hyperactivity disorder flawed?

PMID- 27021056
TI  - Predictors of persistence of ADHD into adulthood: a systematic review of the
      literature and meta-analysis.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is traditionally conceptualized
      as a neurodevelopmental disorder that continues into adulthood in up to half of
      diagnosed cases. In light of current evidence, factors associated with the course
      of the disorder remain unknown. We performed a systematic review of the
      literature searching for risk markers from childhood that predicted the
      persistence of ADHD into adulthood. We reviewed 26,168 abstracts and selected 72
      for full-text review. We identified data from 16 studies, comprising 6 population
      based retrospective samples and 10 clinical follow-ups. We performed meta
      analyses of factors evaluated by at least three studies. Severity of ADHD (OR
      2.33, 95 % CI = 1.6-3.39, p < 0.001), treatment for ADHD (OR 2.09, 95 % CI = 1.04
      4.18, p = 0.037), comorbid conduct disorder (OR 1.85, 95 % CI = 1.06-3.24, p =
      0.030), and comorbid major depressive disorder (OR 1.8, 95 % CI = 1.1-2.95, p =
      0.019) emerged as predictors already presented in childhood for ADHD persistence
      into adulthood. Further, we suggest that cohort studies should be designed to
      clarify such an important question for research and clinical practice.

PMID- 27021057
TI  - Evaluation and simplification of the occupational slip, trip and fall risk
      assessment test.
AB  - OBJECTIVE: The purpose of this investigation is to evaluate the efficacy of the
      occupational slip, trip and fall (STF) risk assessment test developed by the
      Japan Industrial Safety and Health Association (JISHA). We further intended to
      simplify the test to improve efficiency. METHODS: A previous cohort study was
      performed using 540 employees aged >=50 years who took the JISHA's STF risk
      assessment test. We conducted multivariate analysis using these previous results
      as baseline values and answers to questionnaire items or score on physical
      fitness tests as variables. The screening efficiency of each model was evaluated
      based on the obtained receiver operating characteristic (ROC) curve. RESULTS: The
      area under the ROC obtained in multivariate analysis was 0.79 when using all
      items. Six of the 25 questionnaire items were selected for stepwise analysis,
      giving an area under the ROC curve of 0.77. CONCLUSION: Based on the results of
      follow-up performed one year after the initial examination, we successfully
      determined the usefulness of the STF risk assessment test. Administering a
      questionnaire alone is sufficient for screening subjects at risk of STF during
      the subsequent one-year period.

PMID- 27021058
TI  - Correlates of psychological distress, burnout, and resilience among Chinese
      female nurses.
AB  - The present survey investigated the association between resilience, burnout and
      psychological distress among Chinese female nurses. A total of 366 female nurses
      were enrolled in our study. A series of self-reported questionnaires that dispose
      of the following constructs: psychological distress, burnout, and resilience were
      estimated. The hierarchical linear regression models were used to evaluate the
      mediating effect of resilience on the relationship between burnout and
      psychological distress. Results of the survey showed 85.5% nurses experienced
      psychological distress. Resilience was negatively related to psychological
      distress and burnout whereas burnout was positively associated with psychological
      distress. Mediation analysis revealed that resilience could partially mediate the
      relationship between the dimensions of emotional exhaustion, depersonalization,
      and psychological distress. This study highlights the mediator of resilience
      between burnout and psychological distress of female nurses. As such,
      interventions that attend to resilience training may be the focus for future
      clinical and research endeavors.

PMID- 27021059
TI  - The association among ferruginous body, uncoated fibers, asbestos and non
      asbestos fibers in lung tissue in terms of length.
AB  - To demonstrate the correlations between the concentrations of ferruginous body as
      well as uncoated fiber both of which can be observed with phase-contrast
      microscope and the concentration of various inorganic fibers including asbestos
      which requires the observation with TEM or SEM, we measured those indices among
      Japanese and Korean cases. Though the concentration of ferruginous body in lung
      tissue is an important index of asbestos exposure, uncoated fibers observed with
      phase-contrast microscope might be another index especially in such cases with
      relatively low exposure due to their history of living in a general environment.
      However, to establish the reliability of uncoated fibers as an index of asbestos
      exposure, analysis with more cases and from various backgrounds must be carried
      out. 

PMID- 27021060
TI  - Relationship between depressive symptoms and perceived individual level
      occupational stress among Japanese schoolteachers.
AB  - Japanese teachers are mentally and physically burdened with various work
      stressors. This cross-sectional study examined the relationship between
      depressive symptoms and perceived individual level occupational stress including
      role problems among Japanese schoolteachers. This study included 1,006 teachers
      working in public schools in a Japanese city. The Japanese version of Zung's Self
      Rating Depression Scale (SDS) was used to evaluate depressive symptoms, and the
      Generic Job Stress Questionnaire was used to evaluate occupational stress and
      three measures of social support. Subjects with SDS scores of more than 50 were
      categorized into the "depressive group." We examined the relationship between
      depressive symptoms and perceived individual level occupational stress using
      multiple logistic regression analyses. A total of 202 (20.1%) teachers belonged
      to the depressive group. We found that high role ambiguity, high role conflict,
      high quantitative workload, and low social support from family or friends were
      significantly related to depressive symptoms. To moderate role ambiguity and role
      conflict experienced by teachers, it is necessary to clarify the priority order
      of teachers' work. Furthermore, it is necessary to reduce workload by focusing on
      the content of teachers' work and the setting of education itself. Focusing on
      these elements will reduce teachers' depressive symptoms.

PMID- 27021061
TI  - Impact of the number of painful stimuli on life satisfaction among Korean
      industrial accident workers completing convalescence: dual mediating effects of
      self-esteem and sleeping time.
AB  - This study examined the impact of the number of painful stimuli on life
      satisfaction among workers who experienced an industrial accident and
      investigated how self-esteem and sleeping time affected life satisfaction. The
      Korea Workers' Compensation & Welfare Service conducted the first nationwide
      panel survey on occupational health and safety insurance in 2013-2014 through a
      stratified systematic sampling on 2,000 industrial accident workers who completed
      convalescence. Based on the dataset, our study analyzed 1,832 workers
      experiencing an industrial accident after excluding 168 disease patients. For the
      research model analysis, a four-stage hierarchical regression analysis technique
      was applied using the SPSS regression analysis Macro program of PROCESS
      Procedure. To test mediated indirect effects of the self-esteem and sleeping
      time, the bootstrapping technique was applied. Life satisfaction, self-esteem and
      sleeping time decreased as the number of painful stimuli increased. Life
      satisfaction decreased as self-esteem and sleeping time decreased. On balance,
      the partial mediation model confirmed that self-esteem and sleeping time both
      mediate the impact of the number of painful stimuli on life satisfaction.

PMID- 27021062
TI  - A cohort study of the acute and chronic respiratory effects of toner exposure
      among handlers: a longitudinal analyses from 2004 to 2013.
AB  - This study examines the acute and chronic respiratory effects of toner exposure
      based on markers for interstitial pneumonia, oxidative stress and pulmonary
      function tests. A total of 112 subjects working in a Japanese toner and
      photocopier manufacturing company participated in this study in 2004. We annually
      conducted personal exposure measurements, pulmonary function tests, chest X-ray
      examinations, biomarkers, and questionnaires on respiratory symptoms to the
      subjects. We report in this paper the results of the analysis of combined annual
      survey point data from 2004 to 2008 and data from three annual survey points,
      2004, 2008, and 2013. During these survey periods, we observed that none of
      subjects had a new onset of respiratory disease or died of such a disease. In
      both the analyses, there were no significant differences in each biomarker and
      pulmonary function tests within the subjects, nor between a toner-handling group
      and a non-toner-handling group, except for a few results on pulmonary function
      tests. The findings of this study suggest that there were no acute and chronic
      respiratory effects of toner exposure in this cohort group, although the number
      of subjects was small and the level of toner exposure in this worksite was low.

PMID- 27021063
TI  - Therapeutic drug monitoring of mycophenolate in adult solid organ transplant
      patients: an update.
AB  - INTRODUCTION: Mycophenolate (MPA) therapeutic drug monitoring (TDM) in adult
      solid organ transplant recipients was summarized extensively in consensus reports
      published between 2009 and 2011. Thus, this review provides an update on the
      science of MPA TDM over the past 5 years. AREAS COVERED: PubMed and Google
      Scholar (January 2010-January 2016) were searched; relevant articles from
      bibliographies of identified articles were extracted for further review. New
      evidence on TDM-guided dosing in MPA efficacy and toxicity and best approaches
      for estimating MPA area-under-the-curve for TDM were retrieved. EXPERT OPINION:
      Since 2011, little advancement in consensus on MPA TDM has been established for
      any type of solid organ transplant. Lack of systematic studies validating or
      further defining MPA's target range suggests that routine TDM is still
      unwarranted. Accurate, precise, and user-friendly limited sampling strategies
      (LSSs) are available in specific patient populations taking mycophenolate mofetil
      but not enteric-coated mycophenolate sodium. In absence of outcome data, routine
      use of LSSs in MPA TDM still cannot be recommended. Further research should
      attempt to define factors that modulate MPA's pharmacokinetics to elucidate their
      impact on utility of TDM. Future studies should also validate LSSs in larger
      patient populations and demonstrate benefits of LSSs in improving patient
      outcomes.

PMID- 27021064
TI  - Identification of possible light emitters in the gills of a bioluminescent fungus
      Mycena chlorophos.
AB  - The pileus of Mycena chlorophos actively, spontaneously, and continuously emits
      green light. Molecular mechanisms underlying this bioluminescence remain unclear.
      We investigated light emitters in the pileus of M. chlorophos to determine the
      underlying mechanisms. High-performance liquid chromatography-fluorescence
      photodiode array-mass detection analyses showed that actively luminescent gills
      in the pileus exclusively and abundantly possessed riboflavin, riboflavin 5'
      monophosphate, and flavin adenine dinucleotide as green-fluorescent components.
      These components were localized in the bioluminescent region of the gills at the
      microscopic level. Fluorescence spectra of these green-fluorescent components and
      the gills were identical with the spectrum of gill bioluminescence (maximum
      emission wavelength, 525 nm). Thus, our results indicated that the possible light
      emitters in the pileus of M. chlorophos were riboflavin, riboflavin 5'
      monophosphate, and/or flavin adenine dinucleotide. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27021065
TI  - 25-Hydroxyvitamin D concentration and all-cause mortality: the Melbourne
      Collaborative Cohort Study.
AB  - OBJECTIVE: To investigate relationships between mortality and circulating 25
      hydroxyvitamin D (25(OH)D), 25-hydroxycholecalciferol (25(OH)D3) and 25
      hydroxyergocalciferol (25(OH)D2). DESIGN: Case-cohort study within the Melbourne
      Collaborative Cohort Study (MCCS). We measured 25(OH)D2 and 25(OH)D3 in archived
      dried blood spots by LC-MS/MS. Cox regression was used to estimate mortality
      hazard ratios (HR), with adjustment for confounders. SETTING: General community.
      SUBJECTS: The MCCS included 29 206 participants, who at recruitment in 1990-1994
      were aged 40-69 years, had dried blood spots collected and no history of cancer.
      For the present study we selected participants who died by 31 December 2007 (n
      2410) and a random sample (sub-cohort, n 2996). RESULTS: The HR per 25 nmol/l
      increment in concentration of 25(OH)D and 25(OH)D3 were 0.86 (95 % CI 0.78, 0.96;
      P=0.007) and 0.85 (95 % CI 0.77, 0.95; P=0.003), respectively. Of 5108
      participants, sixty-three (1.2 %) had detectable 25(OH)D2; their mean 25(OH)D
      concentration was 11.9 (95 % CI 7.3, 16.6) nmol/l higher (P<0.001). The HR for
      detectable 25(OH)D2 was 1.80 (95 % CI 1.09, 2.97; P=0.023); for those with
      detectable 25(OH)D2, the HR per 25 nmol/l increment in 25(OH)D was 1.06 (95 % CI
      0.87, 1.29; P interaction=0.02). HR were similar for participants who reported
      being in good, very good or excellent health four years after recruitment.
      CONCLUSIONS: Total 25(OH)D and 25(OH)D3 concentrations were inversely associated
      with mortality. The finding that the inverse association for 25(OH)D was
      restricted to those with no detectable 25(OH)D2 requires confirmation in
      populations with higher exposure to ergocalciferol.

PMID- 27021066
TI  - Paraconsistent analysis network applied in the treatment of Raman spectroscopy
      data to support medical diagnosis of skin cancer.
AB  - Paraconsistent logic (PL) is a type of non-classical logic that accepts
      contradiction as a fundamental concept and has produced valuable results in the
      analysis of uncertainties. In this work, algorithms based on a type of PL
      paraconsistent annotated logic of two values (PAL2v)-are interconnected into a
      network of paraconsistent analysis (PANnet). PANnet was applied to a dataset
      comprising 146 Raman spectra of skin tissue biopsy fragments of which 30 spectra
      were determined to represent normal skin tissue (N), 96 were determined to
      represent tissue with basal cell carcinoma, and 19 were determined to be tissue
      with melanoma (MEL). In this database, paraconsistent analysis was able to
      correctly discriminate 136 out of a total of 145 fragments, obtaining a 93.793 %
      correct diagnostic accuracy. The application of PAL2v in the analysis of Raman
      spectroscopy signals produces better discrimination of cells than conventional
      statistical processes and presents a good graphical overview through its
      associated lattice structure. The technique of PAL2v-based data processing can be
      fundamental in the development of a computational tool dedicated to support the
      diagnosis of skin cancer using Raman spectroscopy. 

PMID- 27021067
TI  - Minimally invasive implantable fetal micropacemaker: mechanical testing and
      technical refinements.
AB  - This paper discusses the technical and safety requirements for cardiac pacing of
      a human fetus with heart failure and hydrops fetalis secondary to complete heart
      block. Engineering strategies to meet specific technical requirements were
      integrated into a systematic design and implementation consisting of a novel
      fetal micropacemaker, a percutaneous implantation system, and a sterile package
      that enables device storage and recharging maintenance in a clinical setting. We
      further analyzed observed problems on myocardial fixation and pacing lead fatigue
      previously reported in earlier preclinical trials. This paper describes the
      technical refinements of the implantable fetal micropacemaker to overcome these
      challenges. The mechanical performance has been extensively tested to verify the
      improvement of reliability and safety margins of the implantation system.

PMID- 27021068
TI  - Cultural Norms in Conflict: Breastfeeding Among Hispanic Immigrants in Rural
      Washington State.
AB  - Objectives To examine perceptions, experiences, and attitudes towards
      breastfeeding among Hispanic women living in rural Washington State. Methods
      Twenty parous Hispanic women of low acculturation, aged 25-48 years and residents
      in rural Washington State participated in an exploratory, face-to-face interview.
      Interviews were audio-recorded, translated and transcribed, and analyzed using a
      thematic content analysis approach. Results Nine emergent themes were grouped
      into three overarching categories: (1) Breast is best; (2) Hispanic cultural and
      familial expectations to breastfeed; and (3) Adapting to life in the United
      States: cultural norms in conflict. Women said they were motivated to breastfeed
      because of their knowledge and observations of its health benefits for mother and
      child. They said breastfeeding is ingrained in their Hispanic cultural heritage,
      and infant feeding choices of female family members were particularly influential
      in women's own decision to breastfeed. Women said they experienced embarrassment
      about breastfeeding in the United States and as a result, often chose to initiate
      formula feeding as a complement so as to avoid feelings of shame. Additionally,
      they faced economic pressure to work, key barriers for continued breastfeeding
      among Hispanics in the United States. Conclusions for Practice Knowledge of the
      benefits of breastfeeding for mother and child and longstanding cultural
      practices of breastfeeding are not enough to encourage exclusive breastfeeding to
      6 months among this rural Hispanic population. Continued support through family
      level interventions as well as work place policies that encourage breastfeeding
      are needed for rural Hispanics to reach optimal breastfeeding rates.

PMID- 27021069
TI  - Transcatheter Arterial Embolization with n-Butyl Cyanoacrylate for the Treatment
      of Acquired Uterine Vascular Malformations.
AB  - PURPOSE: The purpose of the study was to evaluate the technique and outcomes of
      transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate (NBCA) for
      the treatment of acquired uterine arteriovenous malformations (AVMs). MATERIALS
      AND METHODS: A retrospective review identified five women treated for suspected
      acquired uterine AVMs with TAE at our institution. Four women (80 %) presented
      with heavy or intermittent vaginal bleeding after obstetric manipulation. One
      woman (20 %) was treated for an incidental AVM discovered on ultrasound after an
      uncomplicated cesarean section. Three women underwent one embolization procedure
      and two women required two procedures. Embolization material included NBCA in six
      procedures (80 %) and gelatin sponge in one procedure (20 %). RESULTS:
      Embolization resulted in angiographic stasis of flow in all seven procedures.
      Four women (80 %) presented with vaginal bleeding which was improved after
      treatment. One woman returned 24 days after unilateral embolization with
      recurrent bleeding, which resolved after retreatment. One woman underwent two
      treatments for an asymptomatic lesion identified on ultrasound. There were no
      major complications. Three women (60 %) experienced mild postembolization pelvic
      pain that was controlled with non-steroidal anti-inflammatory drugs. Three women
      (60 %) had pregnancies and deliveries after embolization. CONCLUSIONS: TAE is a
      safe alternative to surgical therapy for acquired uterine AVMs with the potential
      to maintain fertility. Experience from this case series suggests that NBCA
      provides predictable and effective occlusion.

PMID- 27021070
TI  - Chiral chemistry of metal-camphorate frameworks.
AB  - This critical review presents the various synthetic approaches and chiral
      chemistry of metal-camphorate frameworks (MCamFs), which are homochiral metal
      organic frameworks (MOFs) constructed from a camphorate ligand. The interest in
      this unique subset of homochiral MOFs is derived from the many interesting chiral
      features for both materials and life sciences, such as asymmetrical synthesis or
      crystallization, homochiral structural design, chiral induction, absolute helical
      control and ligand handedness. Additionally, we discuss the potential
      applications of homochiral MCamFs. This review will be of interest to researchers
      attempting to design other homochiral MOFs and those engaged in the extension of
      MOFs for applications such as chiral recognition, enantiomer separation,
      asymmetric catalysis, nonlinear sensors and devices.

PMID- 27021071
TI  - Statin modulation of monocyte phenotype and function: implications for HIV-1
      associated neurocognitive disorders.
AB  - HIV-1-associated neurocognitive disorder (HAND) remains a persistent problem
      despite antiretroviral therapy (ART), largely a result of continued inflammation
      in the periphery and the brain and neurotoxin release from activated myeloid
      cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection,
      play a central role in the pathogenesis of HAND and have parallels with monocyte
      dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG
      CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties
      that contribute to their benefit in atherosclerosis beyond lipid lowering. Here,
      we investigated whether statins would modulate the monocyte phenotype and
      function associated with HIV-1 neuropathogenesis. Treatment ex vivo with
      simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in
      peripheral blood mononuclear cells, as well as in purified monocytes, especially
      CD14++CD16+ "intermediate" monocytes most closely associated with neurocognitive
      disease. Statin treatment also markedly reduced expression of CD163, which is
      also linked to HAND pathogenesis. Finally, simvastatin inhibited production of
      monocyte chemoattractant protein-1 (MCP-1) and other inflammatory cytokines
      following LPS stimulation and reduced monocyte chemotaxis in response to MCP-1, a
      major driver of myeloid cell accumulation in the CNS in HAND. Together, these
      findings suggest that statin drugs may be useful to prevent or reduce HAND in HIV
      1-infected subjects on ART with persistent monocyte activation and inflammation.

PMID- 27021073
TI  - Structure of the full-length TRPV2 channel by cryo-EM.
AB  - Transient receptor potential (TRP) proteins form a superfamily Ca(2+)-permeable
      cation channels regulated by a range of chemical and physical stimuli. Structural
      analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of
      channel activation by agonists through changes in its outer pore region. Though
      homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1
      activators including heat and vanilloids. To further understand the structural
      basis of TRPV channel function, we determined the structure of full-length TRPV2
      at ~5 A resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two
      constrictions, one each in the pore-forming upper and lower gates. The agonist
      free full-length TRPV2 has wider upper and lower gates compared with closed and
      agonist-activated TRPV1. We propose these newly revealed TRPV2 structural
      features contribute to diversity of TRPV channels.

PMID- 27021072
TI  - Apolipoprotein E epsilon4 genotype status is not associated with neuroimaging
      outcomes in a large cohort of HIV+ individuals.
AB  - Previous neuroimaging studies suggest a negative relationship between the
      apolipoprotein (ApoE) epsilon4 allele and brain integrity in human
      immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence
      of this relationship across adulthood remains unclear. The purpose of this study
      is to clarify the discrepancies using a large, diverse group of HIV+ individuals
      and multiple imaging modalities sensitive to HIV. The association of ApoE
      epsilon4 with structural neuroimaging and magnetic resonance spectroscopy (MRS)
      was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy
      Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal
      and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and
      cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of
      myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white
      matter (FWM), frontal gray matter (FGM), and basal ganglia were examined.
      Secondary analyses explored this relationship separately in individuals >=50
      years old (n = 173) and <50 years old (n = 63). No significant differences were
      observed between ApoE epsilon4+ (ApoE epsilon3/epsilon4 and ApoE
      epsilon4/epsilon4) individuals (n = 69) and ApoE epsilon4- (ApoE
      epsilon2/epsilon3 and ApoE epsilon3/epsilon3) individuals (n = 167). When
      individuals were further divided by age, no significant genotype group
      differences were identified in individuals <50 or >=50 years of age on any
      neuroimaging outcome. The ApoE epsilon4 allele did not affect brain integrity in
      this large, diverse sample of HIV+ individuals. The effects of ApoE epsilon4 may
      not be apparent until more advanced ages and may be more prominent when present
      along with other risk factors for neuronal damage.

PMID- 27021076
TI  - Clinical Supervision: invisibility on the contemporary nursing and midwifery
      policy agenda.

PMID- 27021074
TI  - Interpersonal synergies: static prehension tasks performed by two actors.
AB  - We investigated multidigit synergies stabilizing components of the resultant
      force vector during joint performance of a static prehension task by two persons
      as compared to similar tasks performed by a single person using both hands.
      Subjects transferred the instrumented handle from the right hand to the left hand
      (one-person condition) or passed that handle to another person (two-person
      condition) while keeping the handle's position and orientation stationary. Only
      three digits were involved per hand, the thumb, the index finger, and the middle
      finger; the forces and moments produced by the digits were measured by six
      component sensors. We estimated the performance-stabilizing synergies within the
      uncontrolled manifold framework by quantifying the intertrial variance structure
      of digit forces and moments. The analysis was performed at three levels: between
      hands, between virtual finger and virtual thumb (imagined digits producing the
      same mechanical variables as the corresponding actual digits combined) produced
      by the two hands (in both interpersonal and intrapersonal conditions), and
      between the thumb and virtual finger for one hand only. Additionally, we
      performed correlation and phase synchronization analyses of resultant tangential
      forces and internal normal forces. Overall, the one-person conditions were
      characterized by higher amount of intertrial variance that did not affect
      resultant normal force components, higher internal components of normal forces,
      and stronger synchronization of the normal forces generated by the hands. Our
      observations suggest that in two-person tasks, when participants try to achieve a
      common mechanical outcome, the performance-stabilizing synergies depend on non
      visual information exchange, possibly via the haptic and proprioceptive systems.
      Therefore, synergies quantified in tasks using visual feedback only may not be
      generalizable to more natural tasks.

PMID- 27021075
TI  - Improving postural control by applying mechanical noise to ankle muscle tendons.
AB  - The application of subthreshold mechanical vibrations with random frequencies
      (white mechanical noise) to ankle muscle tendons is known to increase muscle
      proprioceptive information and to improve the detection of ankle movements. The
      aim of the present study was to analyze the effect of this mechanical noise on
      postural control, its possible modulation according to the sensory strategies
      used for postural control, and the consequences of increasing postural
      difficulty. The upright stance of 20 healthy young participants tested with their
      eyes closed was analyzed during the application of four different levels of noise
      and compared to that in the absence of noise (control) in three conditions:
      static, static on foam, and dynamic (sinusoidal translation). The quiet standing
      condition was conducted with the eyes open and closed to determine the subjects'
      visual dependency to maintain postural stability. Postural performance was
      assessed using posturographic and motion analysis evaluations. The results in the
      static condition showed that the spectral power density of body sway
      significantly decreased with an optimal level of noise and that the higher the
      spectral power density without noise, the greater the noise effect, irrespective
      of visual dependency. Finally, noise application was ineffective in the foam and
      dynamic conditions. We conclude that the application of mechanical noise to ankle
      muscle tendons is a means to improve quiet standing only. These results suggest
      that mechanical noise stimulation may be more effective in more impaired
      populations.

PMID- 27021077
TI  - Characterization of a type-I crustin with broad-spectrum antimicrobial activity
      from red swamp crayfish Procambarus clarkii.
AB  - Crustins are a family of antimicrobial peptides mainly identified in crustaceans
      and characterized by a whey acidic protein (WAP) domain and an additional glycine
      , cysteine-, or proline-rich region. In this study, we identified and
      characterized PcCru, a new crustin isolated from red swamp crayfish Procambarus
      clarkii. The open reading frame of PcCru was 333 base pairs long and encoded a
      110-residue polypeptide, which contained a signal peptide, a cysteine-rich
      region, and a WAP domain. The architecture and phylogenetic analysis suggested
      that PcCru was a new member of the type-I crustin family. PcCru was highly
      expressed in hemocytes and was significantly induced by viral and bacterial
      stimulations at both the translational and transcriptional levels. The titer of
      PcCru in circulating plasma was also increased considerably by bacterial
      challenge. Recombinant PcCru from both prokaryotic and eukaryotic expression
      systems were generated, and the proteins exhibited broad-spectrum antimicrobial
      activity. Furthermore, PcCru protected crayfish from infection by pathogenic
      bacteria Aeromonas hydrophila in vivo. This study provided new information
      emphasizing the important role of the crustin family in the crustacean
      antibacterial immune response.

PMID- 27021078
TI  - Specific Features of TLR4 Expression in Structural Elements of Placenta in
      Patients with Preeclampsia.
AB  - We studied the expression of TLR4 (Toll-like receptor 4) in the
      syncytiotrophoblast and vascular endothelial cells of terminal and stem placental
      villi in severe preeclampsia and normal pregnancy. In women of both groups, the
      expression of TLR4 was higher in the syncytiotrophoblast that in placental
      endothelial cells. In patients with severe preeclampsia, TLR4 expression in
      endothelial cells of terminal villi was 1.3-fold lower than in normal pregnancy.
      Lower TLR4 expression in the terminal villi endothelium in preeclampsia can
      underlie impaired recognition of damaging molecules with subsequent development
      of endothelial dysfunction and changes in immunological tolerance. 

PMID- 27021079
TI  - Detection of Antileukocytic Antibodies in Blood Serum using Lymphocytes and Latex
      Microspheres Carrying HLA-Antigens upon Alloimmunization of Women with Recurrent
      Pregnancy Loss.
AB  - Anti-HLA-antibodies were detected using cross-reaction of blood serum with
      allogenic T and B cells and latex microspheres coated with HLA-I and HLA-II
      antigens. HLA+ and HLA-sera obtained from women before and after allogeneic
      immunization were tested. The results obtained by these methods significantly
      differed. The test with latex microspheres detected antibodies to HLA-I and HLA
      II antigens with high sensitivity and specificity and can be used for assessment
      of clinical significance of alloantibody detection when using alloimmunization in
      the therapy of gestation disorders. 

PMID- 27021080
TI  - Soft Tissue Regeneration under the Effect of Wound Coating Based on Chitosan
      (Natural Biopolymer).
AB  - We developed wound coating based on natural biopolymer chitosan with additional
      components (ceruloplasmin, L-asparaginic acid, and glycerol). Experiments on
      albino male rats demonstrated its regeneratory, antioxidant, and antibacterial
      effects on wounds involving all layers of the skin. Due to chemical composition
      and buffer component, the biodegraded wound coating optimizes all phases of the
      wound process, accelerates by 22-28% the reparative regeneration, and leads to
      anatomic and functional restoration of injured sites. High absorption capacity
      recommends its use in the treatment of wounds with profuse exudation. 

PMID- 27021081
TI  - Fast Nongenomic Effect of Aldosterone on the Volume of Principal Cells in
      Collecting Tube and Genetic Heterogeneity of Epithelial Sodium Channel in the
      Postnatal Ontogenesis of Rat Kidney.
AB  - The effects of amiloride, epithelial sodium pump inhibitor, on the fast
      nongenomic effect of aldosterone in principal cells of an isolated segment of the
      distal portion of renal collecting tubes were studied in 10-day-old and adult
      rats. Fluorescent staining with Calcein AM showed various effects of amiloride
      (10(-5) M) on the stabilizing effect of aldosterone (10 nM) in hypotonic shock
      (280/140 mOsm/kg). Amiloride attenuated by 30% the effect of aldosterone on the
      amplitude of principal cell swelling in adult animals and almost completely
      abolished this effect in 10-day rats (p<0.05). These age-specific differences in
      the contribution of the distal portion of the collecting tube to the nongenomic
      effect of aldosterone did not depend on genetic heterogeneity of its alpha
      subunit. 

PMID- 27021082
TI  - Adenylyl Cyclase-Associated Protein 1 in the Development of Head and Neck
      Squamous Cell Carcinomas.
AB  - We compared the content of adenylyl cyclase-associated protein 1 (CAP1) in the
      blood and tissues of patients with head and neck squamous cell carcinomas (with
      and without regional metastases), patients with chronic inflammatory diseases
      aggravated by laryngeal and laryngopharyngeal dysplasia, and healthy individuals.
      The data suggest that serum CAP1 concentration correlated with the depth of
      primary tumor invasion and the presence of regional metastases. In cancer
      patients, the serum level of CAP1 was lower than in patients with laryngeal and
      laryngopharyngeal dysplasia, which can be of importance for differential and
      timely diagnostics of malignant tumors. 

PMID- 27021083
TI  - Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation
      Induced Carcinogenesis.
AB  - Toxicogenomic parameters were studied in the blood of female rats after exposure
      to ionizing gamma-radiation in a dose of 4 Gy and chemoprophylaxis with alpha
      difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in
      animals with morphological manifestations of tumor growth under conditions of
      radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects
      was carried out by express method for measurements of blood nucleotid DNA -
      fluorescent indication. The level of hyperaneu/polyploidy increased in the blood
      leukocytes of control rats 30 days after radiation exposure. A significant
      decrease of genotoxicity as a result of drug treatment in comparison with the
      number and multiplicity of tumors in irradiated animals was found only in the
      endocrine and reproductive organs of rats treated by eleutherococcus extract. 

PMID- 27021084
TI  - Effects of Amygdaline from Apricot Kernel on Transplanted Tumors in Mice.
AB  - The effects of amygdaline from apricot kernel added to fodder on the growth of
      transplanted LYO-1 and Ehrlich carcinoma were studied in mice. Apricot kernels
      inhibited the growth of both tumors. Apricot kernels, raw and after thermal
      processing, given 2 days before transplantation produced a pronounced antitumor
      effect. Heat-processed apricot kernels given in 3 days after transplantation
      modified the tumor growth and prolonged animal lifespan. Thermal treatment did
      not considerably reduce the antitumor effect of apricot kernels. It was
      hypothesized that the antitumor effect of amygdaline on Ehrlich carcinoma and LYO
      1 lymphosarcoma was associated with the presence of bacterial genome in the
      tumor. 

PMID- 27021085
TI  - Chromogranin As a Biochemical Marker of Neuroendocrine Tumors.
AB  - Comparative study of plasma chromogranin A levels was carried out in 227 patients
      with neuroendocrine tumors of various locations and 66 normal subjects, men and
      women, by standard ELISA. In patients with tumors of all locations (pancreas,
      stomach, small and large intestine, and lungs), the glycoprotein levels were
      significantly (p<0.000001) higher than in controls. The patients demonstrated
      high variability of chromogranin A levels; the maximum concentrations were
      detected in patients with neuroendocrine tumors of the stomach and lung. The
      highest median values of chromogranin A were found in patients with tumors of the
      small intestine, large intestine, and pancreas. A relationship between secretion
      of chromogranin A and dissemination and activity of the neuroendocrine tumor was
      detected, which was the maximum in patients with metastases in the liver and
      carcinoid syndrome. High diagnostic sensitivity of chromogranin A was shown:
      85.8% for the total group of patients; specificity was 98.5%. These data
      confirmed high efficiency of chromogranin A as the marker of neuroendocrine
      tumors. Detection of this marker promotes more accurate diagnosis and evaluation
      of dissemination of the neuroendocrine tumors. 

PMID- 27021086
TI  - Generation of Reactive Oxygen Species in Peripheral Blood Lymphocytes of Patients
      with Prostate Cancer.
AB  - The study revealed a two-fold elevation of ROS production in peripheral blood
      lymphocytes of the patients with prostate cancer (from 0.48+/-0.04 to 0.93+/-0.12
      rel. units) together with significant variability of individual values. Hormone
      therapy had no effect on the mean and individual ROS levels. In contrast,
      organometallic cytostatics cisplatin and morfozol 2-fold increased ROS generation
      in lymphocytes of patients with prostate cancer above the enhanced level of this
      parameter determined by tumor growth. 

PMID- 27021087
TI  - Antibacterial Effects of Liposomes Containing Phospholipid Cardiolipin and
      Fluoroquinolone Levofloxacin on Mycobacterium tuberculosis with Extensive Drug
      Resistance.
AB  - The effects of liposomes containing phospholipid cardiolipin without antibiotic
      and loaded with levofloxacin on the growth of Mycobacterium tuberculosis with
      extensive drug resistance were studied in vitro. Liposomes consisting of
      cardiolipin alone in a concentration of 335 MUM completely suppressed the growth
      of M. tuberculosis. In order to reduce the minimum inhibitory concentration of
      cardiolipin, complex liposome preparation consisting of
      phosphatidylcholin/cholesterol/cardiolipin and loaded with levofloxacin was
      prepared. Due to this, the cardiolipin concentration was reduced to 33.5 MUM (50
      MUg/ml) and concentration of levofloxacin - to 2 MUg/ml. 

PMID- 27021088
TI  - In Vitro Study of Cytophysiological Characteristics of Multinuclear Macrophages
      from Intact and BCG-Infected Mice.
AB  - Peritoneal macrophages were isolated from intact and BCG-infected BALB/c mice and
      explanted in vitro. Multinuclear macrophages formed in these cultures differed by
      the number of nuclei, expression of apoptosis inductors and regulators (TNF
      alpha, p53 protein, caspase 3, and Bcl-2 protein), and cytophysiological
      characteristics (phagocytic activity, ROS generation, and antimycobacterial
      properties). Our results indicate that the formation of multinuclear macrophages
      is accompanied by induction of apoptosis (p53 signaling pathway) and appearance
      of multinuclear macrophage-derived cells characterized by high phagocytic and
      antimycobacterial activity. 

PMID- 27021089
TI  - Immunochemical Nature of Receptors of Pseudotuberculosis Diagnostic
      Bacteriophage.
AB  - The effect of treatment of Yersinia pseudotuberculosis cells with antibodies of
      various specificities on adhesiveness of pseudotuberculosis bacteriophage was
      analyzed by competitive inhibition technique. Bacteriophage adsorption to
      bacteria was sterically inhibited by monoclonal antibodies to protein epitopes of
      Y. pseudotuberculosis outer membrane. These results suggest that receptors of
      pseudotuberculosis diagnostic bacteriophage are localized on the LPS core of
      microbial cell. 

PMID- 27021090
TI  - CYP1A2 and CYP2D6 Gene Polymorphisms in Schizophrenic Patients with Neuroleptic
      Drug-Induced Side Effects.
AB  - Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system
      were studied in patients with schizophrenia with drug-induced motor disorders and
      hyperprolactinemia against the background of long-term neuroleptic therapy. We
      revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene
      with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4
      and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase
      synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia
      receiving neuroleptics for a long time. 

PMID- 27021091
TI  - Changes in Production of Cytokines by C57Bl/6J Mouse Spleen during Aggression
      Provoked by Social Stress.
AB  - The effect of aggressive behavior shaped under social stress of various durations
      on the production of proinflammatory cytokines by splenic cells was examined on
      C57BL/6J mice. Aggressive mice were characterized by enhanced production of IL-2
      and IFN-gamma (released by T helper type 1 cells) and reduced secretion of TNF
      alpha, whose major producers are monocytes and macrophages. Elevation of IL-2 and
      IFN-gamma in aggressive mice resulted from enhancement of spontaneous and Con A
      stimulated production, the most pronounced effect was demonstrated by the with a
      longer period (20 days) of victories. In contrast, spontaneous production of TNF
      alpha was similar in control and aggressive mice, although LPS-stimulated
      production of this cytokine decreased after 10- and 20-day stress. The possible
      mechanisms of the changes in cytokine production are discussed. 

PMID- 27021092
TI  - Comparison of the Efficiency of Adeprophen and Antidepressants of Various Groups
      on the Model of Reserpine-Induced Depression in Rats.
AB  - A new (aryloxyalkyl)adenine derivative Adeprophen (9-[2-(4
      isopropylphenoxy)ethyl]adenine, VMA-99-82) has a strong antidepressant effect on
      the model of reserpine-induced depression in rats (single dose 4 mg/kg,
      intraperitoneally). This effect manifested in suppression of depression-like
      behavior in the Porsolt forced swimming test (shortening of immobility time and
      increase in immobility latency, number of jumping episodes, and time of active
      swimming) and sucrose consumption/preference test (increase in the consumption of
      20% sucrose solution in g/100 g body weight and percentage of sucrose preference
      in relation to the total fluid preference). Adeprophen had a greater
      antidepressant effect than sertraline and fluoxetine, but was less potent than
      amitriptyline, imipramine, venlafaxine, and to a lesser extent to paroxetine. 

PMID- 27021093
TI  - Neuropeptide Cycloprolylglycine Exhibits Neuroprotective Activity after Systemic
      Administration to Rats with Modeled Incomplete Global Ischemia and in In Vitro
      Modeled Glutamate Neurotoxicity.
AB  - We studied cerebroprotective properties of neuropeptide cycloprolylglycine (1
      mg/kg) administered intraperitoneally to rats with modeled incomplete global
      ischemia rats and neuroprotective properties for HT-22 cells under conditions of
      glutamate toxicity. It was shown that the neuropeptide administered during the
      postischemic period restored the neurological status of rats by preventing
      sensorimotor impairments in the limb-placing test and suppression of locomotor
      activity in the open field test. In in vitro experiments, cycloprolylglycine in
      concentrations of 10(-5)-10(-8) M exhibited pronounced dose-dependent
      neuroprotective activity. The results attest to high cerebro- and neuroprotective
      potential of endogenous peptide cycloprolylglycine. 

PMID- 27021094
TI  - Role of Melatonin in the Regulation of Differentiation of T Cells Producing
      Interleukin-17 (Th17).
AB  - We studied the ability of melatonin in physiological and pharmacological
      concentrations to induce and/or regulate differentiation of T cells producing IL
      17 (Th17). This hormone produced the opposite effect on CD4+T cells, which
      depended on their activation status. Melatonin induced the synthesis of IL-17A by
      intact T cells, but had little effect on activated cells. Melatonin in high
      (pharmacological) concentration decreased the intracellular expression of this
      cytokine under conditions of polyclonal activation. Melatonin had a dose-depended
      effect. Taking into the fact that Th17 cells play an important role in the immune
      defense, it can be suggested that the regulation of their activity by melatonin
      contributes to this process. 

PMID- 27021095
TI  - Detection and Characteristics of Rifampicin-Resistant Isolates of Mycobacterium
      tuberculosis.
AB  - Genotyping and analysis the drug resistance of 59 isolates of M. tuberculosis
      obtained from patients living in Altai Territory were performed using a BACTEC
      MGIT 960 fluorometric system by means of VNTR typing (variable number tandem
      repeat), PCR-RFLP analysis, and sequence analysis. The occurrence frequency was
      highest for isolates of the Beijing family (n=30, 50.8%). Analysis of mutation
      spectrum in the rpoB gene associated with rifampicin resistance revealed the
      major mutation (codon 531 of the rpoB gene) in 93% samples, which allows us to
      use rapid test systems. 

PMID- 27021096
TI  - Changes in Differentiation of Thymic T Cells in the Progeny of Female Mice
      Subjected to Immune System Stimulation during Early Pregnancy.
AB  - Differentiation of T cells was studied in the progeny of female C57Bl/6 mice
      subjected to immunostimulation by administration of concanavalin A or adoptive
      transfer of concanavalin A-activated splenocytes. Acceleration of T cell
      maturation during the prepubertal period and decelerated differentiation during
      the pubertal and post-pubertal periods were revealed. 

PMID- 27021097
TI  - Corticosterone Induces Rapid Increase in the Amplitude of Inhibitory Response in
      Hippocampal Synapses with Asynchronous GABA Release.
AB  - Experiments were performed on cultured slices of rat ventral hippocampus. Using
      extracellular stimulation and patch clamp recording from pyramidal neurons in the
      hippocampal CA1 area, we studied characteristics of GABAergic synapse formed on
      these neurons by cholecystokinin-expressing interneurons. This synapse was
      characterized by asynchronous release of GABA and depolarization-induced
      suppression of inhibitory response. It was observed that administration of
      corticosterone increased the amplitude of evoked inhibitory postsynaptic currents
      in 5 minutes, but the paired ratio did not significantly change. Obtained data
      reflect that corticosterone can induce rapid genome-independent effects on
      inhibitory neurotransmission in one of hippocampal synapses. 

PMID- 27021098
TI  - Profile of microRNA in Blood Plasma of Healthy Humans.
AB  - Analysis of the plasma microRNA profile can be used for the diagnosis of various
      pathological and physiological conditions. Complete microRNA microprofiling is an
      extremely important task. Here we used microarray analysis allowing measurement
      of the expression of 2500 microRNA (MirBase, version 20). About 10% known
      microRNA were found in the plasma. Most of the detected microRNA (69 microRNA;
      ~30%) were encoded by mirtrons. 

PMID- 27021099
TI  - Taxifolin and Fucoidin Abolish the Irradiation-Induced Increase in the Production
      of Reactive Oxygen Species in Rat Aorta.
AB  - We studied changes in ROS content in the aorta of Wistar rats at early terms
      after irradiation in doses equal to single fraction used in tumor radiotherapy
      and the effects of taxifolin and fucoidin, blockers of leukocyte adhesion to
      endothelium, on ROS content. Male rats were exposed to X-rays (200 kW) in doses
      of 1-7.5 Gy. ROS production in aorta segments was measured in 1-48 h after
      irradiation by dichlorodihydrofluorescein oxidation. The content of ROS in the
      aorta of rats exposed to radiation in doses of 1-2.5 Gy increased in 1-24 h after
      irradiation, the peak ROS content was found in 2 h after irradiation. Taxifolin
      (100 MUg/kg dihydroquercetin once a day with drinking water) and fucoidin (10
      mg/kg, i.v.) abolished ROS accumulation. The content of ROS in rat aorta
      increased in 1-24 h after irradiation in doses used for tumor radiotherapy and
      this increase can be determined by leukocyte adhesion to the endothelium. 

PMID- 27021100
TI  - Cardioprotective Effect of Modified Peroxiredoxins in Retrograde Perfusion of
      Isolated Rat Heart under Conditions of Oxidative Stress.
AB  - Antioxidant properties of recombinant peroxiredoxin-6 and chimeric protein PSH
      combining peroxidase and superoxide dismutase activities were studied on the
      model of retrograde perfusion of isolated rat heart under conditions of H2O2
      induced oxidative stress. The exogenous antioxidant proteins exhibited
      cardioprotective properties manifested in heart rate normalization, maintenance
      of contractile activity of the myocardium, and prevention of H2O2-induced LPO in
      oxidative stress. Localization of peroxiredoxin-6 and PSH in the cardiac tissue
      was determined and myocardial structures most effectively protected by the
      antioxidant enzymes from ischemia/reperfusion-induced damages were identified.
      The results suggest that modified peroxiredoxins are promising components of
      perfusion media for preservation of isolated organs. 

PMID- 27021101
TI  - Effect of 5-Fluorouracil on Thymidine Phosphorylase Activity in Model Experiment.
AB  - Variations in thymidine phosphorylase activity in rat liver were studied in 1, 3,
      6, 12, and 24 h after intraperitoneal bolus injection of 5-fluorouracil. Enzyme
      activity was measured by HPLC. A 2-fold decrease in enzyme activity was observed
      3 h after 5-fluorouracil administration and persisted for 12 h. This additional
      effect of the cytostatic should be taken into account in choosing chemotherapy
      protocol. 

PMID- 27021102
TI  - Role of BK(Ca) Potassium Channels in the Mechanisms of Modulatory Effects of IL
      10 on Hypoxia-Induced Changes in Activity of Hippocampal Neurons.
AB  - We studied the contribution of large conductance Ca(2+)-activated potassium
      channels (BKCa) in the mechanisms of neuromodulatory effects of anti-inflammatory
      cytokine IL-10 on hypoxiainduced changes in activity of CA1 pyramidal neurons in
      rat hippocampus. We used the method of registration of population spikes from CA1
      pyramidal neurons in hippocampal slices before, during, and after exposure to
      short-term episodes of hypoxia. Selective blocker (iberiotoxin) and selective
      activator of BKCa (BMS-191011) were used to evaluate the contribution of these
      channels in the mechanisms of suppressive effects of IL-10 on changes in neuronal
      activity during hypoxia and development of post-hypoxic hyperexcitability. It was
      shown that BKCa are involved in the modulatory effects of IL-10 on hypoxia
      induced suppression of activity of CA1 pyramidal neurons in the hippocampus and
      development of post-hypoxic hyperexcitability in these neurons. 

PMID- 27021103
TI  - Changes in Cerebral Blood Flow in the Postischemic Period.
AB  - Experiments on Wistar rats showed that blood flow in the cortex and subcortical
      brain structures was not completely restored within 21 days after transient
      ischemia caused by bilateral carotid artery occlusion with controlled
      hypotension. After 7 days of reinfusion, the end-diastolic blood flow velocity
      increases with simultaneous decrease in pulsation index, which indicates the
      decrease in peripheral vascular resistance. During the following 14 days,
      peripheral blood resistance increases, as was seen from the increased peak
      systolic blood flow velocity, mean blood flow velocity over the heart cycle, and
      pulsation index. These changes are likely a delayed manifestation of ischemic
      reperfusion injury to brain microvessels (no-reflow phenomenon) and are
      determined by changes in blood rheologiy and pial vessel lumen. 

PMID- 27021104
TI  - Effect of Repeated 1-h Episodes of Immobilization Stress on Activity of
      Glucocorticoid Metabolism Enzymes in the Liver.
AB  - Differences in corticosterone level associated with different activity of
      glucocorticoid-oxidizing enzymes in the liver were revealed in rats exposed to
      stress. Pro-inflammatory changes in the liver were associated with enhanced CYP3A
      dependent monooxygenation. 

PMID- 27021106
TI  - Systemic Effects of Testosterone: Hormonal and Behavioral Mechanisms.
AB  - We studied the effects of food deprivation, spatial complexity of environment,
      and cognitive strain on blood level of testosterone in male (C57Bl/6*DBA/2)F1
      mice. Hormone concentration decreased after exposure to any factor and this
      decrease depended on combined impact to the factors. Testosterone concentration
      was most sensitive to cognitive strain against the background of food
      deprivation. The total response of testosterone under conditions of enriched
      environment and activation of social interactions in the form of neurotic and
      aggressive behavior provoked by food deprivation was not equal to the sum of
      individual effects of these factors. Testosterone response to combined exposure
      to external and internal factors reflected systemic effect. 

PMID- 27021105
TI  - Depression of Macrophages Modifies Serum Lipid Profile in Hyperlipidemia.
AB  - Suppression of functional activity of macrophages by gadolinium chloride,
      suppressing the macrophage population and the endocytosis velocity, was studied
      in vivo. Injection of GdCl3 led to an increase in serum cholesterol
      concentration. Preliminary injection of GdCl3 to mice with lipidemia 24 h before
      poloxamer 407 reduced the concentrations of triglycerides and LDL during marked
      depression of macrophages (in 24 h). Macrophage repopulation (days 5, 7) was
      associated with development of a trend to an increase of triglyceride and LDL
      levels. lectron microscopic study of Kupffer cells after injection of poloxamer
      407 and its combination with gadoliniun chloride detected the intralysosomal
      accumulation syndrome in these cells (formation of auto- and
      heterophagolysosomes). Activity of cathepsin B, characteristic of macrophages,
      reduced 24 h after injections of GdCl3 and poloxamer 407 alone and restored in
      response to their combination. 

PMID- 27021107
TI  - Free Radical Oxidation in Rat Myocardium after Maximum Permissible Hepatic
      Resection.
AB  - Free radical oxidation in rat myocardial homogenate was studied by
      chemiluminescent assay during the early terms after maximum permissible liver
      resection. During this period, activation of free radical oxidation was biphasic.
      The critical terms characterized by dramatic intensification of free radical
      oxidation in the myocardium are the first hour and the first day after surgery.
      The period from 3 to 12 h after surgery, in which the indices of
      chemiluminescence decrease, can be tentatively termed as the period of "putative
      wellbeing". Normalization of the free radical oxidation processes in the
      myocardium occurred by day 7 after surgery. 

PMID- 27021108
TI  - Effect of Hypothermia-Induced Respiratory Arrest on Cerebral Circulation in Rats.
AB  - Intravital microscopy was employed to examine cerebral circulation in rats
      assessed by blood flow in the venules with diameter of 10-30 MU during immersion
      hypothermia continued to the moment of respiratory arrest and for 10 min
      thereafter. Circulation in the cerebral microvessels continued during severe
      hypothermia, and it went on even after hypothermic respiratory arrest while the
      heart was beating. In pial venules, the blood continued to fl ow for 8-10 min
      after respiratory arrest. 

PMID- 27021109
TI  - Dynamics of the Development of Amnesia Caused by Disruption of Memory
      Reconsolidation by Neurotransmitter Receptors Antagonists.
AB  - The dynamics of amnesia development under conditions of memory reconsolidation
      disruption by serotonin receptor antagonist methiothepin or NMDA glutamate
      receptor antagonist MK-801 was studied in snails trained in conventional food
      aversion. In 2 days after training, injection of methiothepin or MK-801 before
      reminder induced amnesia development. During repeated training in 3 days after
      amnesia induction, the skill was formed more rapidly than during the initial
      training. During repeated training in 10 days after administration of
      methiothepin and reminder, the dynamics of habit formation was similar to that
      during initial learning. At the same time, repeated training in 10 days after MK
      801 administration and reminder did not result in long-term memory formation.
      Disruption of reconsolidation of conditioned food aversion memory by antagonists
      of serotonin or NMDA glutamate receptors led to the development of different
      types of amnesia that had similar strengthening gradient at the early stages, but
      differed by the possibility of memory formation during re-training at the late
      stage. 

PMID- 27021110
TI  - Activity of the Hypothalamic-Pituitary-Adrenal System in Prenatally Stressed Male
      Rats on the Experimental Model of Post-Traumatic Stress Disorder.
AB  - Using the experimental model of post-traumatic stress disorder (stress-restress
      paradigm), we studied the dynamics of activity of the hypothalamic-pituitary
      adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to
      restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were
      subjected to combined stress and subsequent restress exhibited not only increased
      sensitivity of HPAS to negative feedback signals (manifested under restress
      conditions), but also enhanced stress system reactivity. These changes persisted
      to the 30th day after restress. Under basal conditions, the number of cells in
      the hypothalamic paraventricular nucleus of these animals expressing
      corticotropin-releasing hormone and vasopressin was shown to decrease
      progressively on days 1-30. By contrast, combined stress and restress in control
      animals were followed by an increase in the count of CRH-immunopositive cells in
      the magnocellular and parvocellular parts of the paraventricular nucleus and
      number of vasopressin-immunopositive cells in the magnocellular part of the
      nucleus (to the 10th day after restress). Our results indicate a peculiar level
      of functional activity of HPAS in prenatally stressed males in the stress
      restress paradigm: decreased activity under basal conditions and enhanced
      reactivity during stress. 

PMID- 27021111
TI  - Oxytocin-Induced Changes in Monoamine Level in Symmetric Brain Structures of
      Isolated Aggressive C57Bl/6 Mice.
AB  - Changes in activity of monoaminergic systems of the left and right brain
      hemispheres after administration of saline and oxytocin were studied in male
      C57Bl/6 mice subjected to social isolation. The concentrations of dopamine,
      norepinephrine, serotonin, and their metabolites dihydroxyphenylacetic,
      homovanillic, and 5-hydroxyindoleacetic acids were measured in the cerebral
      cortex, hippocampus, olfactory tubercle, and striatum of the left and right brain
      hemispheres by HPLC. In isolated aggressive males treated intranasally with
      saline, the content of serotonin and 5-hydroxyindoleacetic acid was significantly
      higher in the right hippocampus. Oxytocin reduces aggression caused by long-term
      social isolation, but has no absolute ability to suppress this type of behavior.
      Oxytocin reduced dopamine content in the left cortex and serotonin content in the
      right hippocampus and left striatum. Furthermore, oxytocin evened the revealed
      asymmetry in serotonin and 5-hydroxyindoleacetic acid concentrations in the
      hippocampus. At the same time, asymmetry in dopamine concentration appeared in
      the cortex with predominance of this transmitter in the right hemisphere. The
      data are discussed in the context of lateralization of neurotransmitter systems
      responsible for intraspecific aggression caused by long-term social isolation. 

PMID- 27021112
TI  - Histological and morphological aspects of reproduction in the sandbar shark
      Carcharhinus plumbeus in the U.S. south-eastern Atlantic Ocean and Gulf of
      Mexico.
AB  - The reproduction of the sandbar shark Carcharhinus plumbeus in the U.S. south
      eastern Atlantic Ocean including the Gulf of Mexico was examined using a
      combination of histological and morphological characteristics of C. plumbeus
      collected through fishery-dependent and -independent sampling programmes (n =
      1,567). Indices of maturity were constructed using measurements of gonads,
      reproductive tracts and claspers, and sandbar sharks exhibited 50% maturity sizes
      of 140 and 148 cm fork length for males and females respectively. Gonado-somatic
      indices and variation in reproductive tract condition were used to determine
      seasonal trends in reproduction of mature C. plumbeus. Sandbar sharks have
      discrete seasonal reproductive cycles in which males produce sperm from January
      to May with a peak in May and females develop eggs from January to May with
      ovulation occurring in June. Females were shown to exhibit a >2 year reproductive
      cycle. Embryonic development was assessed through measurements of masses and
      lengths of uterine contents. Gestation was 12 months, from July to the following
      June, with parturition in late June. This research highlights a difference from
      previously reported data on the periodicity of female reproduction in C. plumbeus
      in the U.S. south-eastern Atlantic Ocean and Gulf of Mexico, which may have major
      effects on future C. plumbeus stock management. 

PMID- 27021113
TI  - Super-flat supercontinuum generation from a Tm-doped fiber amplifier.
AB  - Super-flat supercontinua are generated from a double clad Tm-doped fiber
      amplifier. Two different laser configurations are investigated and compared. In
      the direct-output configuration, the long-wavelength edge of the supercontinuum
      spectra is extended to beyond 2.65 MUm with a 10 dB bandwidth of 740 nm. In the
      passive pigtail configuration, the generated supercontinuum features excellent
      flatness with an intensity difference smaller than 1 dB in the wide central
      spectral range from 1.98 MUm to 2.41 MUm.

PMID- 27021115
TI  - A superhydrophilic nitinol shape memory alloy with enhanced anti-biofouling and
      anti-corrosion properties.
AB  - This work reports on a nitinol (NiTi) surface modification scheme based on a
      chemical oxidation method, and characterizes its effects on wetting, biofouling
      and corrosion. The scheme developed is also compared with selected previous
      oxidation methods. The proposed method turns NiTi into superhydrophilic in ~5
      min, and the static contact angle and contact angle hysteresis were measured to
      be ~7 degrees  and ~12 degrees , respectively. In the PRP (platelet rich plasma)
      test, platelet adhesion was reduced by ~89% and ~77% respectively, compared with
      the original NiTi and the NiTi treated with the previous chemical oxidation
      scheme. The method developed provides a high (~1.1 V) breakdown voltage, which
      surpasses the ASTM standard for intervascular medical devices. It also provides
      higher superhydrophilicity, hemo-compatibility and anti-corrosion resistance than
      previous oxidation schemes, with a significantly reduced process time (~5 min),
      and will help the development of high performance NiTi devices. 

PMID- 27021114
TI  - HPLC profiling, antioxidant and in vivo anti-inflammatory activity of the ethanol
      extract of Syzygium jambos available in Bangladesh.
AB  - BACKGROUND: Syzygium jambos has been used as a traditional medicine for the
      treatment of inflammatory diseases in Bangladesh. The study investigates the high
      performance liquid chromatography (HPLC) profiling of phenolic compounds, and
      evaluates the antioxidant and anti-inflammatory activities of ethanol extract of
      S. jambos available in Bangladesh. METHODS: The extract was subjected to HPLC for
      the identification and quantification of the major bioactive polyphenols present
      in S. jambos. Antioxidant activity was determined using 2, 2'-azino bis-3
      ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging, reducing power
      assay, total antioxidant capacity, total phenolic and flavonoid content.
      Furthermore, the anti-inflammatory effect of the extract in rats for two
      different test models: carrageenan and histamine-induced paw edema was inspected.
      RESULTS: High levels of catechin hydrate and rutin hydrate (99.00 and 79.20
      mg/100 g extract, respectively) and moderate amounts of ellagic acid and
      quercetin (59.40 and 69.30 mg/100 g extract, respectively) were quantified in
      HPLC. Catechin hydrate from this plant extract was determined for the first time
      through HPLC. For ABTS scavenging assay, the median inhibition concentration
      (IC50) value of S. jambos was 57.80 ug/ml, which was significant to that of
      ascorbic acid (12.01 ug/ml). The maximum absorbance for reducing power assay was
      found to be 0.4934. The total antioxidant capacity, phenolic and flavonoid
      contents were calculated to be 628.50 mg/g of ascorbic acid, 230.82 mg/g of
      gallic acid and 11.84 mg/g of quercetin equivalent, respectively. At a dose of
      400 mg/kg, a significant acute anti-inflammatory activity (P < 0.01) was observed
      in rats for both the test models with a reduction in the paw volume of 58.04 and
      53.95 %, in comparison to those of indomethacin (62.94 and 65.79 %),
      respectively. CONCLUSIONS: The results suggest that the phenolic and flavonoid
      compounds are responsible for acute anti-inflammatory and antioxidant activities
      of S. jambos.

PMID- 27021116
TI  - When should infants start to EAT? Is it time to LEAP? And other nutty insights.

PMID- 27021117
TI  - Biomarkers for diagnosing asthma: a smoking gun?

PMID- 27021118
TI  - Chronic inflammatory airway diseases: the central role of the epithelium
      revisited.
AB  - The respiratory epithelium plays a critical role for the maintenance of airway
      integrity and defense against inhaled particles. Physical barrier provided by
      apical junctions and mucociliary clearance clears inhaled pathogens, allergens or
      toxics, to prevent continuous stimulation of adaptive immune responses. The
      "chemical barrier", consisting of several anti-microbial factors such as lysozyme
      and lactoferrin, constitutes another protective mechanism of the mucosae against
      external aggressions before adaptive immune response starts. The reconstruction
      of damaged respiratory epithelium is crucial to restore this barrier. This review
      examines the role of the airway epithelium through recent advances in health and
      chronic inflammatory diseases in the lower conducting airways (in asthma and
      chronic obstructive pulmonary disease). Better understanding of normal and
      altered epithelial functions continuously provides new insights into the
      physiopathology of chronic airway diseases and should help to identify new
      epithelial-targeted therapies. 

PMID- 27021121
TI  - Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in
      Japanese asthmatics.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) induced by inflammatory
      cytokines and iNOS activity in bronchial epithelial cells is a major determinant
      of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to
      investigate the association of iNOS promoter gene polymorphisms and FeNO levels
      in Japanese asthmatics before the introduction of asthma treatment. METHODS:
      Asthmatics were recruited from Fukushima Medical University Hospital. Genotyping
      of the pentanucleotide repeat (CCTTT)n and seven previously detected single
      nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The
      relationships between the genotypes and FeNO levels before the introduction of
      asthma treatment were compared. RESULTS: In 91 asthmatics, the number of
      microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution.
      According to this distribution, asthmatics were divided into two groups:
      genotypes with at least one long allele with more than 14 repeats (L/s or L/L)
      and genotypes with both short alleles with 14 or fewer repeats (s/s). No
      significant differences were observed in each parameter between the two groups.
      The mean FeNO level before treatment was significantly higher in the L/s or L/L
      subjects than in the s/s subjects. After treatment, the lowest FeNO level did not
      differ between the two groups. Three SNPs detected in the Japanese subjects were
      not associated with FeNO levels. CONCLUSIONS: The number of CCTTT repeats in the
      iNOS promoter region was associated with FeNO levels in asthmatics before
      treatment, suggesting the importance of iNOS genotype in the clinical application
      of FeNO for asthmatics.

PMID- 27021119
TI  - B cells establish, but do not maintain, long-lived murine anti-peanut IgE(a).
AB  - BACKGROUND: Peanut allergy (PNA) has been reported to be transferred to tolerant
      recipients through organ and bone marrow (BM) transplantation. The roles T and B
      cells play in establishing, and the roles B cell subsets play in maintaining
      lifelong anti-peanut IgE levels are unknown. OBJECTIVES: To determine the
      cellular requirements for the transfer of murine PNA and to determine the role
      CD20(+) cells play in maintaining long-lived anti-peanut IgE levels. METHODS: We
      developed a novel adoptive transfer model to investigate the cellular
      requirements for transferring murine PNA. We also treated peanut-allergic (PA)
      mice with anti-CD20 antibody and measured IgE levels throughout treatment.
      RESULTS: Purified B220(+) cells from PA splenocytes and purified CD4(+) cells
      from naive (NA) splenocytes are the minimal requirements for the adoptive
      transfer of PNA. Prolonged treatment of allergic mice with anti-CD20 antibody
      results in significant depletion of B cell subsets but does not affect anti
      peanut IgE levels, symptoms, or numbers of IgE antibody secreting cells (ASCs) in
      the BM. Adoptive transfer of BM and spleen cells from allergic donors treated
      with anti-CD20 antibody does not result in the transfer of PNA in NA recipients,
      demonstrating that anti-CD20 antibody treatment depletes B cells capable of
      differentiating into peanut-specific IgE ASCs. CONCLUSIONS AND CLINICAL
      RELEVANCE: Peanut allergy can be established in a NA hosts with B220(+) cells
      from PA donors and CD4(+) cells from peanut-NA donors. However, long-term
      depletion of B220(+) cells with anti-CD20 antibody does not affect anti-peanut
      IgE levels. These results highlight a novel role for B cells in the development
      of PNA and provide evidence that long-lived anti-peanut IgE levels may be
      maintained by long-lived ASCs.

PMID- 27021122
TI  - A case of black garlic-induced pneumonia as an adverse reaction.

PMID- 27021123
TI  - Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its
      Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase
      Fluorescent Probe.
AB  - Tyrosinase is regarded as an important biomarker of melanoma cancer, and its
      metabolism is closely related to some severe skin diseases such as vitiligo.
      Since tyrosinase is mainly located in the melanosomes of melanocytes, a probe
      that can specifically detect and image tysosinase in melanosomes would be in
      urgent demand to study the behavior of the enzyme in cells, but unfortunately, no
      melanosome-targeting tyrosinase fluorescent probe has been reported so far to the
      best of our knowledge. In this work, we have developed such a new probe, Mela
      TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as
      a tyrosinase reaction group. The probe exhibits not only a highly sensitive and
      selective off-on response to tyrosinase via oxidization cleavage, but also an
      accurate targeting ability toward the acidic organelles of melanosomes and
      lyososomes, which is validated by colocalization experiments with mCherry-tagged
      melanosomes as well as DND-99 (a commercial dye). The probe has been used to
      image the relative contents of tyrosinase in different cells. Notably, because of
      the tyrosinase deficiency in normal lysosomes, the probe only fluoresces in
      melanosomes in principle although it can accumulate in other acidic organelles
      like lysosomes. By virtue of this property, the misdistribution of tyrosinase
      from melanosomes to lysosomes in murine melanoma B16 cells under the stimulation
      of inulavosin is imaged in real time for the first time. Moreover, the
      upregulation of melanosomal tyrosinase in live B16 cells under the stimulation of
      psoralen/ultraviolet A is detected with our probe, and this upregulation is
      further verified by standard colorimetric assay. The probe provides a simple,
      visual method to study the metabolism of tyrosinase in cells and shows great
      potential in clinical diagnosis and treatments of tyrosinase-associated diseases.

PMID- 27021125
TI  - Lateral subtalar fracture-dislocation with maintenance of the talonavicular
      joint: case study, diagnosis and management.

PMID- 27021126
TI  - Combined use of ECMO and hemodialysis in the case of contrast-induced biphasic
      anaphylactic shock.

PMID- 27021127
TI  - Modified traumatic bleeding severity score: early determination of the need for
      massive transfusion.
AB  - BACKGROUND: Determination of the need for massive transfusion (MT) is essential
      for early activation of a MT protocol. The Traumatic Bleeding Severity Score
      (TBSS) predicts the need for MT accurately, but takes time to determine because
      systolic blood pressure after a 1000mL of crystalloid infusion is used. The aim
      of this study is to determine the how well the Modified TBSS (age, sonography,
      pelvic fracture, serum lactate and systolic blood pressure on arrival) predicts
      the need for MT (accuracy). METHODS: This is a single-center retrospective study
      of trauma patients (Injury Severity Score ?16) admitted between 2010 and 2014.
      The TBSS, the Trauma Associated Severe Hemorrhage (TASH) Score, and the Modified
      TBSS were calculated. MT is defined as ?10 U packed red blood cell transfusion
      within 24hours of injury, and the predictive value of the need for MT was
      compared by area under the receiver operating characteristic curve (AUC) analysis
      among three scores. RESULTS: Three hundred patients were enrolled, and MT given
      to 25% of patients. Although the AUC of the TBSS was higher than that of the TASH
      score (0.956 vs 0.912, P=.006) and the Modified TBSS (0.956 vs 0.915, P=.001),
      there was no difference between the AUC of the Modified TBSS and the TASH score.
      The Modified TBSS has high accuracy, within an AUC >0.9. CONCLUSION: The
      predictive value of the Modified TBSS of the need for MT is still high and is
      equivalent to the TASH score. The Modified TBSS is calculated earlier in
      resuscitation than the original TBSS.

PMID- 27021128
TI  - Succinylcholine in an ED patient with unanticipated hyperkalemia.

PMID- 27021129
TI  - A study on energy drinks and realistic results concordant with daily clinical
      practice.

PMID- 27021130
TI  - Characteristics and diagnostic pitfalls of spontaneous visceral artery dissection
      in the emergency department.
AB  - BACKGROUND: Spontaneous visceral artery dissection (VAD) is a rare disease that
      mainly occurs in the superior mesenteric artery and celiac artery. However, VAD
      has been detected more frequently in the past several years because of the
      increasing use of computed tomography (CT) for the evaluation of abdominal
      symptoms. A prompt diagnosis and referral to a specialist should be made, because
      VAD occasionally causes critical bowel ischemia. However, there is no well
      established management approach. We performed a retrospective analysis to
      evaluate the characteristics and prognoses of patients diagnosed with VAD.
      METHODS: We retrospectively examined data on patients who visited the Emergency
      Department (ED) at Fukui Prefectural Hospital, and were diagnosed with VAD using
      enhanced CT scanning from April 2004 to March 2015. All data were collected from
      the hospital's electronic medical records. We analyzed the clinical
      characteristics, comorbidity, risk factors, imaging findings, and treatment of
      patients. RESULTS: Fifty-six patients were identified (superior mesenteric
      artery: 40 patients, celiac artery: 16 patients). The median age of the patients
      was 54 years (range, 32-86 years) and 89.3% were men. The majority of the
      patients complained of abdominal pain (37 patients, 66%). Thirty-nine of the
      patients (69.6%) were hospitalized. All hospitalized patients received
      conservative treatment initially. Three patients received endovascular therapy,
      and 2 patients received surgery. No fatal cases were observed. Twenty-eight
      patients presented with ED at their initial visit, and 8 cases (29%) were
      undiagnosed on their initial visit by emergency physicians, though enhanced CT
      scans were obtained. CONCLUSION: Patients with VAD often present with sudden
      onset abdominal pain. Most patients were managed successfully with conservative
      treatment. No fatal cases were observed; however, some cases were missed, even
      with an enhanced CT scan. It is necessary to include VAD among the differential
      diagnoses of acute abdominal pain. Patients with VAD should be referred to a
      specialist, because this disease occasionally causes critical bowel ischemia,
      necessitating surgical intervention.

PMID- 27021131
TI  - A quick and easy delirium assessment for nonphysician research personnel.
AB  - OBJECTIVES: Delirium in the emergency department (ED) is an emerging field of
      research. Most ED research infrastructures utilize lay personnel to collect data,
      but delirium assessments that can be reliably performed by nonphysicians are
      lacking. We evaluated the diagnostic performance of the modified Brief Confusion
      Assessment Method (modified bCAM) for this purpose. METHODS: This was a secondary
      analysis of a prospective observational study that enrolled ED patients 65years
      or older. The original bCAM was a brief (<2minutes) delirium assessment that
      assessed for inattention by asking the patient to recite the months backward from
      December to July. It was modified by adding the Vigilance A ("squeeze my hand
      when you hear the letter 'A'") to the inattention assessment. The elements of the
      modified bCAM were performed by a research assistant (RA) and emergency
      physician. The reference standard for delirium was a psychiatrist assessment
      performed within 3hours using Diagnostic and Statistical Manual of Mental
      Disorder, Fourth Edition, Text Revision criteria. All assessors were blinded to
      each other. Sensitivities and specificities with their 95% confidence intervals
      (CIs) were calculated for the RA and emergency physician. RESULTS: Of the 406
      patients enrolled, 50 (12%) were delirious. The modified bCAM was 82.0% (95% CI,
      71.4%-92.6%) sensitive and 96.1% (95% CI, 94.0%-98.1%) specific when performed by
      the RA. The emergency physician's modified bCAM exhibited similar diagnostic
      performance. CONCLUSIONS: The modified bCAM may be a feasible and accurate method
      for nonphysicians to assess for delirium. Future studies are needed to confirm
      these findings.

PMID- 27021132
TI  - [Influence of steroid hormones on the production of two inflammatory markers, IL
      12 and nitric oxide, in Behcet's disease].
AB  - Uveitis is one of the major diagnostic criteria of Behcet's disease (BD), a
      chronic systemic inflammatory pathology with an uncertain etiology. Since uveitis
      is more frequent in male patients, we assessed the level and the effect of sex
      hormones on inflammatory responses during BD. Peripheral blood was taken from 19
      patients with BD and 20 healthy subjects. Estradiol, testosterone and cortisol
      were measured in plasma by ELISA. Circulating mononuclear cells (PBMC) were
      obtained on gradient density and cultured with or without the three hormones for
      24h at 37 C. IL-12 and nitric oxide (NO) were measured in vivo and ex vivo by
      ELISA and a modified Griess method, respectively. We confirmed the significantly
      higher in vivo and in vitro levels of NO and IL-12 in BD in comparison to
      controls (P<0.05). We also found that circulating cortisol was lower in BD while
      sex hormones did not show any significant difference between the groups (P>0.05).
      In vitro, NO was reduced by estradiol and cortisol and increased by testosterone
      in both sexes. In contrast, while IL-12 production showed the same production
      profile as NO in women, estradiol and cortisol failed to reduce IL-12 levels in
      men. Our results may explain in part the differences observed between men and
      women in disease clinical expression. In fact, male patients seem to have
      defective IL-12 down-regulation by estradiol and cortisol that increases Th1
      immune responses. This may be implicated in the severe expression of BD in men. 

PMID- 27021133
TI  - Improving Automated Annotation of Benthic Survey Images Using Wide-band
      Fluorescence.
AB  - Large-scale imaging techniques are used increasingly for ecological surveys.
      However, manual analysis can be prohibitively expensive, creating a bottleneck
      between collected images and desired data-products. This bottleneck is
      particularly severe for benthic surveys, where millions of images are obtained
      each year. Recent automated annotation methods may provide a solution, but
      reflectance images do not always contain sufficient information for adequate
      classification accuracy. In this work, the FluorIS, a low-cost modified consumer
      camera, was used to capture wide-band wide-field-of-view fluorescence images
      during a field deployment in Eilat, Israel. The fluorescence images were
      registered with standard reflectance images, and an automated annotation method
      based on convolutional neural networks was developed. Our results demonstrate a
      22% reduction of classification error-rate when using both images types compared
      to only using reflectance images. The improvements were large, in particular, for
      coral reef genera Platygyra, Acropora and Millepora, where classification recall
      improved by 38%, 33%, and 41%, respectively. We conclude that convolutional
      neural networks can be used to combine reflectance and fluorescence imagery in
      order to significantly improve automated annotation accuracy and reduce the
      manual annotation bottleneck. 

PMID- 27021134
TI  - Single molecule study of initial structural features on the amyloidosis process.
AB  - We employed an alpha-hemolysin (alpha-HL) nanopore as a single-molecule tool to
      investigate the effects of initial structure on the amyloidosis process. The
      differences in the initial structure of two beta-amyloid (Abeta) peptides
      (Abeta25-35 and Abeta35-25) could be distinguished in real-time due to their
      characteristic blockades. More importantly, the distinct aggregate dynamics for
      these two kinds of Abeta fragments can be readily analyzed by monitoring the
      blockade frequency over time. 

PMID- 27021135
TI  - Drug driven psychoses and legal responsibility or insanity in six Western Pacific
      nations.
AB  - Prompted by four questions, forensic mental health clinicians from Russia, China,
      Japan, Hong Kong, Australia and New Zealand provided information on both the
      legislative basis and current practice concerning the relationship between legal
      insanity, intoxication and drug induced psychosis in their six Pacific Rim
      Countries which account for nearly 20% of the world's population. Details of the
      survey for each contributing nation are provided. While there are significant
      variations in practice that have been shaped by regional legal, clinical and
      cultural influences there is considerable similarity in the legislation
      underpinning how these issues are considered. Consequently there remain similar
      challenges for each nation. In none of the legislative bases was the issue of
      drug induced psychosis specifically addressed. The authors conclude that evolving
      pharmaco-neuropsychiatric knowledge, societal values and patterns of substance
      misuse require nations to consider developments in scientific and clinical
      knowledge to support their interpretations of the relationship between altered
      mental states as a result of substance use and the legal construct of insanity.

PMID- 27021136
TI  - Older offenders deemed criminally irresponsible in Flanders (Belgium):
      Descriptive results from a retrospective case note study.
AB  - INTRODUCTION: In Belgium, offenders who are deemed criminally irresponsible for
      their criminal actions because of mental illness or intellectual disability are
      subject to a specific safety measure with the dual objective of protecting
      society and providing mandated care to the offender. While Belgian law requires
      that offenders who are deemed criminally irresponsible should be in a hospital,
      clinic or other appropriate institution outside of prison, in practice, about one
      third of all such offenders still reside in prison. Whether imprisoned or living
      in settings outside prison, there is a dearth of knowledge on the characteristics
      of the aging population among the criminally irresponsible offenders. OBJECTIVE:
      This paper aimed to explore the characteristics of older offenders categorized as
      criminally irresponsible in Flanders (northern Belgium) with a focus on the
      differences between imprisoned older offenders deemed criminally irresponsible
      and their peers who are residing outside prison. METHOD: A retrospective case
      note study of all offenders deemed criminally irresponsible, >60years of age
      (n=174), was conducted in the four Commissions of Social Defense, which implement
      the procedure in the case of those deemed criminally irresponsible in Flanders.
      The files were screened for (1) demographic characteristics, (2) criminal history
      as well as (3) mental and physical health issues. RESULTS: One-fourth of the
      population were >70years of age. A total of 30.5% were in prison. Compared to
      their non-imprisoned peers, the imprisoned offenders had a history of having
      committed more serious violent crimes towards persons, such as homicides and
      sexual crimes. In addition, imprisoned older offenders categorized as criminally
      irresponsible are characterized more explicitly by personality traits that are
      likely to reduce their chances of being transferred to more appropriate settings
      in the community. IMPLICATIONS: A comprehensive and systematic screening of all
      older offenders deemed criminally irresponsible with regard to health needs and
      social functioning, including age-related deterioration, alcoholism, and other
      causes of social disadvantages, is warranted to detect potentially hidden
      problems.

PMID- 27021137
TI  - A lipidomics investigation into the intervention of celastrol in experimental
      colitis.
AB  - Celastrol is well known for its anti-inflammatory and anti-cancer effects. In
      this study, the efficacy of celastrol against dextran sulfate sodium (DSS)
      induced inflammatory bowel disease (IBD) in mice was established and the
      mechanism was investigated using lipidomics. Celastrol treatment significantly
      alleviated DSS-induced colitis in mice, as revealed by the body weight, colon
      length, scores of rectal bleeding and diarrhea, serum TNF-alpha level, and
      histological analysis results. Lipidomics analysis based on UPLC/MS revealed
      characteristic changes in the metabolic profiles of the colitis mice, with
      altered levels of lipid markers associated with IBD, including LPC18 : 0, LPC18 :
      1, LPC18 : 2, sphingomyelin (SM), and increased LPC18 : 0/LPC18 : 1 and LPC18 :
      0/LPC18 : 2 ratios. For the celastrol-treated colitis mice, however, levels of
      the above lipid markers were restored, together with recovered saturated
      LPC/unsaturated LPC ratios. Accordingly, using GC-MS analysis, increased stearic
      acid (C18 : 0)/oleic acid (C18 : 1) and stearic acid (C18 : 0)/linoleic acid (C18
      : 2) ratios were observed in colitis mice, which were later recovered after
      celastrol treatment. Quantitative real-time PCR analysis revealed that the liver
      expression of stearoyl-coenzyme A desaturase 1 (SCD1), the key enzyme controlling
      the desaturation of saturated fatty acid, was dramatically inhibited in IBD mice,
      and was obviously recovered after celastrol treatment. These results suggest that
      the increased saturated LPC/unsaturated LPC (and saturated fatty acid/unsaturated
      fatty acid) ratios associated with SCD1 down-regulation could be regarded as
      biomarkers of colitis, and celastrol alleviates DSS-induced colitis partially via
      up-regulation of SCD1, restoring the altered balance between stearic acid- and
      oleic acid-derived lipid species, which plays an important role in alleviating
      colitis. In all, this study provided the scientific basis for further development
      of celastrol in treating IBD.

PMID- 27021138
TI  - Alcohol-triggered signs of migraine: An animal model.
AB  - We describe an animal model where characteristics of migraine can be triggered by
      alcohol administration. In rats chronically implanted with a cannula overlying
      the transverse sinus, we applied potassium chloride (KCl) (or saline) to the
      meninges to sensitize trigeminovascular afferents. We assessed effects of
      repeated KCl application on animal behavior using conditioned place avoidance
      paradigm. In KCl-treated rats we discovered that alcohol injections (0.2 mg/kg),
      but not saline, resulted in the development of extracephalic allodynia and signs
      of ongoing pain.

PMID- 27021139
TI  - Pneumocystis jirovecii pneumonia complicating the progress of a patient with
      glioblastoma multiforme receiving temozolomide.

PMID- 27021140
TI  - Pseudochylotorax without pleural thickening associated with rheumatoid arthritis.

PMID- 27021141
TI  - Human Herpes Virus 8 Unrelated Bilateral Primary Effusion Lymphoma in a Patient
      With Chronic Fluid Overload.

PMID- 27021143
TI  - Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in
      Hispanic Americans.
AB  - Multiple sclerosis can affect pediatric patients. Our aim was to compare
      characteristics between pediatric-onset multiple sclerosis and adult-onset
      multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of
      363 Hispanic American multiple scleroses cases; demographic and clinical
      characteristics were analyzed. A total of 110 Hispanic patients presented with
      multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most
      common presenting symptoms for both was optic neuritis. Polyfocal symptoms,
      seizures, and cognitive symptoms at presentation were more prevalent in pediatric
      onset multiple sclerosis (P <= .001). Transverse myelitis was more frequent in
      adult-onset multiple sclerosis (P <= .001). Using multivariable analysis,
      pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence
      interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95%
      confidence interval 0.3-1.03, P = .006) were less likely to have severe
      ambulatory disability. Results suggest that pediatric-onset multiple sclerosis
      and adult-onset multiple sclerosis in Hispanics have differences that could be
      important for treatment and prognosis.

PMID- 27021142
TI  - Initial report of near-infrared fluorescence imaging as an intraoperative adjunct
      for lymph node harvesting during robot-assisted laparoscopic gastrectomy.
AB  - INTRODUCTION: Adequate lymphadenectomy is a fundamental aspect of oncologically
      sound gastrectomies. Robot-assisted laparoscopic gastrectomy is a minimally
      invasive alternative that allows functional imaging to be easily integrated to
      the surgical field and may aid in intraoperative identification of lymphovascular
      bundles. METHODS: Indocyanine green application and near-infrared fluorescence
      imaging were used during robot-assisted laparoscopic gastrectomy as an adjunct
      for the identification of relevant lymph node basins in real time. RESULTS: A
      total of 31 patients were included. Twenty-nine gastrectomies were performed for
      adenocarcinoma and two wedge resections for neuroendocrine tumors. The mean lymph
      node retrieval was twenty-nine (range 17-61) for adenocarcinoma and five for
      neuroendocrine tumors. In all cases, at least five lymph nodes were seen along
      the main nodal basins, which provided real time intraoperative feedback regarding
      lymph node identification. Average time for indocyanine green application and
      functional imaging was less than 10 min. CONCLUSIONS: Near-infrared fluorescent
      imaging may provide an improved method to help visualize lymph nodes
      intraoperatively during robot-assisted laparoscopic gastrectomy, thus adding a
      potentially valuable adjunct for lymphadenectomy and overall lymph node
      retrieval. J. Surg. Oncol. 2016;113:768-770. (c) 2016 Wiley Periodicals, Inc.

PMID- 27021144
TI  - Use of a Virtual-Technological Sailing Program to Prepare Children With
      Disabilities for a Real Sailing Course: Effects on Balance and Quality of Life.
AB  - Sailing might produce a positive effect on a patient's general health and become
      an integrated part of rehabilitation. Our hypothesis was that a specific
      technological rehabilitation program might be used to prepare a group of disabled
      subjects for sailing. Seventeen patients (age range: 9-20) with impairments in
      motor coordination and balance and 15 healthy subjects participated in the study.
      The study was divided into the virtual-technological sailing phase, theory
      practice phase, and sports phase. Proprioceptive platforms were used to evaluate
      balance, and the Child Health Questionnaire-PF50 was used to evaluate quality of
      life. Trunk displacement and the center of pressure velocity improved
      significantly after the virtual-technological sailing program. As regards quality
      of life, the physical and psychosocial score significantly improved at the end of
      the program. A technological rehabilitation training improved balance in disabled
      subjects and may be used to prepare them for a real sailing course. Sailing
      improves the quality of life of disabled subjects and could be used in the
      rehabilitation.

PMID- 27021145
TI  - A Comparison of Midazolam, Lorazepam, and Diazepam for the Treatment of Status
      Epilepticus in Children: A Network Meta-analysis.
AB  - Midazolam, lorazepam, and diazepam were recommended as emergent initial therapy
      for status epilepticus. However, there are no current studies to confirm the best
      agent for pediatric status epilepticus. We compared the efficacy of midazolam,
      lorazepam, and diazepam in treating pediatric status epilepticus using a network
      meta-analysis method. In total, 16 randomized controlled trials containing 1821
      patients were included. Nonintravenous midazolam, intravenous lorazepam, and
      intravenous diazepam were more successful in achieving seizure cessation when
      compared with nonintravenous diazepam (odds ratio = 2.23, 95% credibility
      interval: 1.62, 3.10; odds ratio = 2.71, 95% credibility interval: 1.25, 5.89;
      odds ratio = 2.65, 95% credibility interval: 1.12, 6.29; respectively). Among
      lorazepam, midazolam, and diazepam, midazolam had the highest probability
      (surface under the cumulative ranking area [SUCRA] = 0.792) of achieving seizure
      cessation, and lorazepam had the largest probability (surface under the
      cumulative ranking area = 0.4346) of being the best treatment in reduction of
      respiratory depression. In conclusion, nonintravenous midazolam and intravenous
      lorazepam were superior to intravenous or nonintravenous diazepam, and
      intravenous lorazepam was at least as effective as nonintravenous midazolam in
      treating pediatric status epilepticus.

PMID- 27021146
TI  - Psychosocial Predictors of Relapse Among Patients with Alcohol Problems.
AB  - BACKGROUND: Alcohol abuse is a common problem that is socially, psychologically
      and economically devastating to health of individuals. OBJECTIVES: the purpose of
      this study was to examine the interrelationship between alcohol relapse, self
      efficacy, perceived social support, and perceived stress among individual
      diagnosed with alcohol dependence. METHODS: A cross-sectional descriptive
      correlational design was utilized to collect data using self-administered
      questionnaire from a purposeful sample of 111 Jordanians diagnosed with alcohol
      dependence. Data collected in regards to self efficacy, perceived social support,
      and perceived stress. RESULTS: patients reported moderate to severe psychological
      distress, moderate level of self-efficacy, and moderate perception of social
      support. The analysis also showed that self-efficacy and perceived social support
      from other and from friends have negative and not significant correlation with
      relapse. Also age had significant and positive correlation with relapse. Marital
      status and duration of alcohol dependence were significant predictors of relapse.
      CONCLUSION: Stress and socio-demographic characteristic are significant factors
      to be considered while planning for alcohol relapse prevention.

PMID- 27021147
TI  - Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement
      in Patients with Opioid Dependence on Methadone Maintenance Treatment.
AB  - BACKGROUND: While chronic pain has been said to impact patient's response to
      methadone maintenance treatment for opioid dependence, the reported findings are
      inconsistent. These discrepancies may be a direct result of variations in the
      measurement of chronic pain or definitions of response to methadone treatment.
      The goal of this study is to evaluate the association between pain and substance
      use behaviour to determine the real impact of comorbid pain in the methadone
      population. We also aim to examine sources of variation across the literature
      with a specific focus on the measurement of pain. METHODS/DESIGN: We performed a
      systematic review using an electronic search strategy across CINAHL, MEDLINE, Web
      of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane
      Reviews and the Cochrane Central Register of Controlled Trials databases. Title,
      abstract, as well as full text screening and extraction were performed in
      duplicate. Studies evaluating the association between chronic pain and methadone
      maintenance treatment response were eligible for inclusion in this review. Using
      a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA)
      research collaborative, we assessed the reliability of patient self-reported pain
      and the validated Brief Pain Inventory (BPI) assessment tool. RESULTS: After
      screening 826 articles we identified five studies eligible for full text
      extraction, of which three showed a significant relationship between the presence
      of pain and the increase in substance abuse among patients on methadone for the
      treatment of opioid dependence. Studies varied largely in the definitions and
      measurement of both pain and response to treatment. Results from our validation
      of pain measurement in the GENOA sample (n=297) showed the use of a simple self
      reported pain question is highly correlated to the use of the BPI. Simply asking
      patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity,
      84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the
      Pearson chi(2) was 37.3; (p<0.0001). DISCUSSION: The field of addiction medicine
      is at a lack of consensus as to the real effect of chronic pain on treatment
      response among opioid dependent patients. Whether it be the lack of a single
      "gold standard" measurement of response, or a lack of consistent measurement of
      pain, it is difficult to summarize and compare the results of these relatively
      small investigations. In comparison to the BPI, use of the simple self-reported
      pain has lower sensitivity for identifying patients with pain, suggesting the
      inconsistencies in these studies may result from differences in pain measurement.
      Future validation studies of pain measurement are required to address the
      predictive value of self-reported pain.

PMID- 27021148
TI  - New Insights into the Pathophysiology of Painful Bladder Syndrome: From Humans to
      Animals and Into the Future.

PMID- 27021150
TI  - Microstructural and compositional contributions towards the mechanical behavior
      of aging human bone measured by cyclic and impact reference point indentation.
AB  - The assessment of fracture risk often relies primarily on measuring bone mineral
      density, thereby accounting for only a single pathology: the loss of bone mass.
      However, bone's ability to resist fracture is a result of its biphasic
      composition and hierarchical structure that imbue it with high strength and
      toughness. Reference point indentation (RPI) testing is designed to directly
      probe bone mechanical behavior at the microscale in situ, although it remains
      unclear which aspects of bone composition and structure influence the results at
      this scale. Therefore, our goal in this study was to investigate factors that
      contribute to bone mechanical behavior measured by cyclic reference point
      indentation, impact reference point indentation, and three-point bending. Twenty
      eight female cadavers (ages 57-97) were subjected to cyclic and impact RPI in
      parallel at the unmodified tibia mid-diaphysis. After RPI, the middiaphyseal
      tibiae were removed, scanned using micro-CT to obtain cortical porosity (Ct.Po.)
      and tissue mineral density (TMD), then tested using three-point bending, and
      lastly assayed for the accumulation of advanced glycation end-products (AGEs).
      Both the indentation distance increase from cyclic RPI (IDI) and bone material
      strength index from impact RPI (BMSi) were significantly correlated with TMD (r=
      0.390, p=0.006; r=0.430, p=0.002; respectively). Accumulation of AGEs was
      significantly correlated with IDI (r=0.281, p=0.046), creep indentation distance
      (CID, r=0.396, p=0.004), and BMSi (r=-0.613, p<0.001). There were no significant
      relationships between tissue TMD or AGEs accumulation with the quasi-static
      material properties. Toughness decreased with increasing tissue Ct.Po. (r=-0.621,
      p<0.001). Other three-point bending measures also correlated with tissue Ct.Po.
      including the bending modulus (r=-0.50, p<0.001) and ultimate stress (r=-0.56,
      p<0.001). The effects of Ct.Po. on indentation were less pronounced with IDI
      (r=0.290, p=0.043) and BMSi (r=-0.299, p=0.037) correlated modestly with tissue
      Ct.Po. These results suggest that RPI may be sensitive to bone quality changes
      relating to collagen.

PMID- 27021151
TI  - Zoledronate prevents lactation induced bone loss and results in additional post
      lactation bone mass in mice.
AB  - In rodents, lactation is associated with a considerable and very rapid bone loss,
      which almost completely recovers after weaning. The aim of the present study was
      to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation
      induced bone loss, and if Zln interferes with recovery of bone mass after
      lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the
      following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery,
      Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days,
      then the pups were removed, and thereafter recovery took place for 28days. Zln,
      100MUg/kg, was given s.c. on the day of delivery, and again 4 and 8days later.
      Mechanical testing, MUCT, and dynamic histomorphometry were performed. At L4,
      lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant,
      p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (
      29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation
      induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro
      architectural and mechanical properties was found 28days after weaning in vehicle
      treated mice. Interestingly, the recovery group treated with Zln during the
      lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05)
      compared with virgin controls. Similar results were found at the proximal tibia
      and femur. This indicates that Zln did not interfere with the bone formation
      taking place after weaning. On this background, we conclude that post-lactation
      bone formation is not dependent on a preceding lactation induced bone loss.

PMID- 27021152
TI  - Targeted Inhibition of Glutamine-Dependent Glutathione Metabolism Overcomes Death
      Resistance Induced by Chronic Cycling Hypoxia.
AB  - AIMS: Tumor hypoxia is a major biological factor causing poor patient outcome.
      Evidence is increasing that improved protection against reactive oxygen species
      (ROS) participates in therapy resistance of chronically hypoxic cancer cells. We
      aimed at characterizing the relevance of improved ROS defense for radiation
      resistance of cancer cells with tolerance to cycling anoxia/re-oxygenation stress
      ("anoxia-tolerant") and at designing rational treatment strategies for overcoming
      the resulting therapy resistance by targeting the underlying mechanisms
      identified in an in vitro model. RESULTS: We demonstrate that chronic exposure of
      NCH-H460 lung adenocarcinoma, DU145 prostate cancer, and T98G glioblastoma cells
      to cycling anoxia/re-oxygenation stress induced upregulation of the aspartate
      aminotransferase glutamic-oxaloacetic transaminase (GOT1), particularly in RAS
      driven anoxia-tolerant NCI-H460 cells. Altered glutamine utilization of the
      anoxia-tolerant cancer cells contributed to the observed decrease in cellular ROS
      levels, the increase in cellular glutathione levels, and improved cell survival
      on ROS-inducing treatments, including exposure to ionizing radiation.
      Importantly, targeting glutamine-dependent antioxidant capacity or glutathione
      metabolism allowed us to hit anoxia-tolerant cancer cells and to overcome their
      increased resistance to radiation-induced cell death. Targeting glutathione
      metabolism by Piperlongumine also improved the radiation response of anoxia
      tolerant NCI-H460 cells in vivo. INNOVATION: Improved antioxidant capacity
      downstream of up-regulated GOT1-expression is a characteristic of anoxia-tolerant
      cancer cells and is predictive for a specific vulnerability to inhibition of
      glutamine utilization or glutathione metabolism, respectively. CONCLUSION:
      Unraveling the molecular alterations underlying improved ROS defense of anoxia
      tolerant cancer cells allows the design of rational strategies for overcoming
      radiation resistance caused by tumor cell heterogeneity in hypoxic tumors.
      Antioxid. Redox Signal. 25, 89-107.

PMID- 27021153
TI  - An intraoperative technique to reduce superficial surgical site infections in
      circular stapler-constructed laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) has been established as
      one of the most effective treatments for morbid obesity. Surgical site infections
      are the most common complication after LRYGB surgery. OBJECTIVE: To compare the
      superficial surgical site infections (sSSI) rate before and after the
      implementation of our intraoperative technique. SETTING: Academic medical center.
      METHODS: Our intraoperative technique relies on sterile coverage of the circular
      stapler, sterile specimen-bag retrieval of the gastrojejunostomy enteric remnant,
      and port site Penrose drainage. We analyzed our sSSI outcomes before and after
      implementation of our technique in all LRYGBs performed by a single surgeon from
      2009 to 2015. We took into account patient age; sex; baseline body mass index
      (BMI); smoking status; and co-morbidities such as diabetes, hypertension, and
      hyperlipidemia. chi(2) and multivariate analysis were performed. RESULTS: We
      performed 486 LRYGBs in 2009-2015. The cohort before implementation of our
      technique (group 1) included 164 patients (33.7%) and the cohort after
      implementation (group 2) included 322 patients (66.3%). Both groups were similar
      in age, sex, smoking status, and rates of diabetes and hyperlipidemia but
      differed in BMI, operative time, and prevalence of hypertension. Hypertension was
      not a confounder for sSSI (P = .35). The sSSI rate was 9.15% for group 1 and
      3.42% for group 2 (P = .0079). Controlling for BMI and operative time,
      multivariate analysis revealed a significant reduction in sSSI (odds ratio 2.98
      [95% CI 1.33-6.69]) with our technique. CONCLUSIONS: We describe a reproducible
      intraoperative technique that significantly reduces sSSI in LRYGB procedures. Our
      technique has the potential of hastening postoperative recovery.

PMID- 27021154
TI  - Hospital variation in rates of acid-reducing medication use after laparoscopic
      sleeve gastrectomy.

PMID- 27021149
TI  - Public health and international drug policy.

PMID- 27021155
TI  - Mitral valve repair: Is the cheese factory moving?

PMID- 27021156
TI  - The future of stem cells: Should we keep the "stem" and skip the "cells"?
AB  - There is accumulating evidence that the cardioprotective effects of stem cells
      are predominantly mediated by the release of a blend of factors, possibly
      clustered into extracellular vesicles, which harness endogenous repair pathways.
      The clinical translation of this concept requires the identification of the cell
      secreted signaling biomolecules and an appropriate transfer method. The study by
      Wei and colleagues has addressed these 2 requirements by showing that the
      epicardial delivery of a collagen patch loaded with the cardiokine follistatin
      like 1 improved left ventricular function in animal models of myocardial
      infarction. Beyond the choice of the factor and its vehicle, these data may open
      a new therapeutic path whereby the functionalization of biomaterials by bioactive
      compounds could successfully substitute for the current cell transplantation
      based strategy.

PMID- 27021157
TI  - Too big or too small?

PMID- 27021158
TI  - Isolated ascending aorta endografting: Another brush for the aortic
      reconstruction artist.

PMID- 27021159
TI  - Variation in osteon histomorphometrics and their impact on age-at-death
      estimation in older individuals.
AB  - Histomorphometric studies have reported relations between osteon size and age;
      however, data focused on the shape of osteons is sparse. The purpose of this
      study was to determine how osteon circularity (On.Cr) varies with age in
      different skeletal elements. Regression analysis was used to evaluate the
      relationship between age and osteon shape and size. We hypothesized that age
      would be negatively related to osteon size (area, On.Ar) and positively related
      to osteon shape (On.Cr). On.Cr and On.Ar were determined for the ribs and femora
      of 27 cadaveric specimens with known age-at-death. As predicted, age was
      significantly related to osteon size and shape for both the femur and rib. With
      age, there was a decrease in size and an increase in circularity. No relationship
      between sex and On.Cr was detected. An age predicting model, including On.Cr,
      On.Ar and OPD, is proposed to improve our ability to estimate age-at-death,
      especially for older individuals. 

PMID- 27021161
TI  - Sites of Anesthetic Inhibitory Action on a Cationic Ligand-Gated Ion Channel.
AB  - Pentameric ligand-gated ion channels have been identified as the principal target
      of general anesthetics (GA), whose molecular mechanism of action remains poorly
      understood. Bacterial homologs, such as the Gloeobacter violaceus receptor
      (GLIC), have been shown to be valid functional models of GA action. The GA
      bromoform inhibits GLIC at submillimolar concentration. We characterize bromoform
      binding by crystallography and molecular dynamics (MD) simulations. GLIC's open
      form structure identified three intra-subunit binding sites. We crystallized the
      locally closed form with an additional bromoform molecule in the channel pore. We
      systematically compare binding with the multiple potential sites of allosteric
      channel regulation in the open, locally closed, and resting forms. MD simulations
      reveal differential exchange pathways between sites from one form to the other.
      GAs predominantly access the receptor from the lipid bilayer in all cases.
      Differential binding affinity among the channel forms is observed; the pore site
      markedly stabilizes the inactive versus active state. 

PMID- 27021160
TI  - Crystal Structure and Proteomics Analysis of Empty Virus-like Particles of Cowpea
      Mosaic Virus.
AB  - Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently
      being utilized as reagents in various biomedical and nanotechnology applications.
      Here, we report the crystal structure of CPMV eVLPs determined using X-ray
      crystallography at 2.3 A resolution and compare it with previously reported cryo
      electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although
      the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist
      significant differences at the C terminus of the small (S) subunit. The intact C
      terminus of the S subunit plays a critical role in enabling the efficient
      assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle
      formation. In addition, we report the results of mass spectrometry-based
      proteomics analysis of coat protein subunits from CPMV eVLPs and virions that
      identify the C termini of S subunits undergo proteolytic cleavages at multiple
      sites instead of a single cleavage site as previously observed. 

PMID- 27021162
TI  - A Model for the Molecular Mechanism of an Engineered Light-Driven Protein
      Machine.
AB  - Controllable protein-based machines and materials are of considerable interest
      for diverse biotechnological applications. We previously re-engineered an ATP
      driven protein machine, a group II chaperonin, to function as a light-gated
      nanocage. Here we develop and test a model for the molecular mechanism of the re
      engineered chaperonin, which undergoes a large-scale closed to open
      conformational change triggered by reversible photo-isomerization of a site
      specifically attached azobenzene crosslinker. In silico experiments using all
      atom simulations suggest that rigid body motions of protein subdomains couple the
      length changes of the crosslinker to rearrangements of the nucleotide-binding
      pocket, leading to cage opening. We tested this model by designing a mutant for
      which the orientation of the two protein subdomains forming the nucleotide
      binding pocket is directly controlled by the crosslinker, and confirmed
      successful reversible photoswitching in vitro. The model probes the
      conformational cycle of group II chaperonins and offers a design principle for
      engineering other light-driven protein-based molecular machines.

PMID- 27021163
TI  - The Y9P Variant of the Titin I27 Module: Structural Determinants of Its Revisited
      Nanomechanics.
AB  - The titin I27 module from human cardiac titin has become a standard in protein
      nanomechanics. A proline-scanning study of its mechanical clamp found three
      mechanically hypomorphic mutants and a paradoxically hypermorphic mutant
      (I27Y9P). Both types of mutants have been commonly used as substrates of several
      protein unfoldase machineries in studies relating protein mechanostability to
      translocation or degradation rates. Using single-molecule force spectroscopy
      based on atomic force microscopy, polyprotein engineering, and steered molecular
      dynamics simulations, we show that, unexpectedly, the mechanostability of the Y9P
      variant is comparable to the wild type. Furthermore, the NMR analysis of
      homomeric polyproteins of this variant suggests that these constructs may induce
      slight structural perturbations in the monomer, which may explain some minor
      differences in this variant's properties; namely the abolishment of the
      mechanical unfolding intermediate and a reduced thermal stability. Our results
      clarify a previously reported paradoxical result in protein nanomechanics and
      contribute to refining our toolbox for understanding the unfolding mechanism used
      by translocases and degradation machines. 

PMID- 27021165
TI  - Telocytes in the reproductive organs: Current understanding and future
      challenges.
AB  - Over the past decades, we were witnessing spectacular molecular medicine
      advances. However, many of the reproductive medicine problems, such as fertility
      issues and premature birth still represent major challenges for obstetrics and
      gynecology worldwide. A new cell population - the telocytes (TCs) - were
      described in the interstitial space of many organs, and their possible
      implications in many important physiological and pathological processes should
      not be overlooked. In this article, we present a historical perspective outlining
      the landmarks in the discovery, evolution and achievements in the field of TCs
      over the last ten years. We focused on the potential roles of TCs in
      morphogenesis and maintenance of the normal three-dimensional architecture of
      tissues, in controlling of the stem cell microenvironment, as having anti
      inflammatory and cancer-suppressing properties, participating in the immune
      surveillance, all mediated by direct homo- and heterocellular junctions or
      indirectly by extracellular vesicle release. Here, we overview the advances on
      TCs research in the reproductive organs (uterus and fallopian tube), accessory
      reproductive organs of female (mammary glands) and the temporary endocrine organ
      placenta.

PMID- 27021166
TI  - RNA metabolism and regulation of virulence programs in fungi.
AB  - The development of RNA imaging techniques and the establishment of systems
      biology approaches, together with the improvement of large-scale RNA-protein
      crosslinking immunoprecipitation protocols have enormously expanded our knowledge
      of RNA networks and the function of RNA-binding proteins in metazoans and model
      yeasts. In pathogenic fungi, the biological role of the vast majority of RNA
      binding proteins and non-coding RNAs is still largely unknown. However, many RNA
      dependent mechanisms which shape fungal pathogenicity have been defined. Here,
      advances made in this field are reviewed and further theories of biological
      significance are discussed in the light of latest findings.

PMID- 27021164
TI  - Molecular Plasticity of the Human Voltage-Dependent Anion Channel Embedded Into a
      Membrane.
AB  - The voltage-dependent anion channel (VDAC) regulates the flux of metabolites and
      ions across the outer mitochondrial membrane. Regulation of ion flow involves
      conformational transitions in VDAC, but the nature of these changes has not been
      resolved to date. By combining single-molecule force spectroscopy with nuclear
      magnetic resonance spectroscopy we show that the beta barrel of human VDAC
      embedded into a membrane is highly flexible. Its mechanical flexibility exceeds
      by up to one order of magnitude that determined for beta strands of other
      membrane proteins and is largest in the N-terminal part of the beta barrel.
      Interaction with Ca(2+), a key regulator of metabolism and apoptosis,
      considerably decreases the barrel's conformational variability and kinetic free
      energy in the membrane. The combined data suggest that physiological VDAC
      function depends on the molecular plasticity of its channel. 

PMID- 27021167
TI  - Cryptosporidium within-host genetic diversity: systematic bibliographical search
      and narrative overview.
AB  - Knowledge of the within-host genetic diversity of a pathogen often has broad
      implications for disease management. Cryptosporidium protozoan parasites are
      among the most common causative agents of infectious diarrhoea. Current
      limitations of in vitro culture impose the use of uncultured isolates obtained
      directly from the hosts as operational units of Cryptosporidium genotyping. The
      validity of this practice is centred on the assumption of genetic homogeneity of
      the parasite within the host, and genetic studies often take little account of
      the within-host genetic diversity of Cryptosporidium. Yet, theory and
      experimental evidence contemplate genetic diversity of Cryptosporidium at the
      within-host scale, but this diversity is not easily identified by genotyping
      methods ill-suited for the resolution of DNA mixtures. We performed a systematic
      bibliographical search of the occurrence of within-host genetic diversity of
      Cryptosporidium parasites in epidemiological samples, between 2005 and 2015. Our
      results indicate that genetic diversity at the within-host scale, in the form of
      mixed species or intra-species diversity, has been identified in a large number
      (n=55) of epidemiological surveys of cryptosporidiosis in variable proportions,
      but has often been treated as a secondary finding and not analysed. As in
      malaria, there are indications that the scale of this diversity varies between
      geographical regions, perhaps depending on the prevailing transmission pathways.
      These results provide a significant knowledge base from which to draw alternative
      population genetic structure models, some of which are discussed in this paper.

PMID- 27021168
TI  - Heterogeneous astrocytes: Active players in CNS.
AB  - Astrocytes, the predominant cell type that are broadly distributed in the brain
      and spinal cord, play key roles in maintaining homeostasis of the central nerve
      system (CNS) in physiological and pathological conditions. Increasing evidence
      indicates that astrocytes are a complex colony with heterogeneity on morphology,
      gene expression, function and many other aspects depending on their spatio
      temporal distribution and activation level. In pathological conditions,
      astrocytes differentially respond to all kinds of insults, including injury and
      disease, and participate in the neuropathological process. Based on current
      studies, we here give an overview of the roles of heterogeneous astrocytes in
      CNS, especially in neuropathologies, which focuses on biological and functional
      diversity of astrocytes. We propose that a precise understanding of the
      heterogeneous astrocytes is critical to unlocking the secrets about pathogenesis
      and treatment of the mazy CNS.

PMID- 27021169
TI  - Physical activity and exercise attenuate neuroinflammation in neurological
      diseases.
AB  - Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD),
      and Parkinson's disease (PD) are devastating neurological disorders, which
      increasingly contribute to global morbidity and mortality. Although the
      pathogenic mechanisms of these conditions are quite diverse, chronic
      neuroinflammation is one underlying feature shared by all these diseases. Even
      though the specific root causes of these diseases remain to be identified,
      evidence indicates that the observed neuroinflammation is initiated by unique
      pathological features associated with each specific disease. If the initial acute
      inflammation is not resolved, a chronic neuroinflammatory state develops and
      ultimately contributes to disease progression. Chronic neuroinflammation is
      characterized by adverse and non-specific activation of glial cells, which can
      lead to collateral damage of nearby neurons and other glia. This misdirected
      neuroinflammatory response is hypothesized to contribute to neuropathology in
      MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance
      of whole body and brain health, may also beneficially modify neuroimmune
      responses. Since PA has neuroimmune-modifying properties, and the common
      underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we
      hypothesize that PA could minimize brain diseases by modifying glia-mediated
      neuroinflammation. This review highlights current evidence supporting the disease
      altering potential of PA and exercise through modifications of neuroimmune
      responses, specifically in MDD, SCH, AD and PD.

PMID- 27021170
TI  - GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG
      Abnormalities and Enhances Seizure Susceptibility.
AB  - Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental
      disorder associated with severe epilepsy. We previously implicated GABAergic
      deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical
      hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate
      consequences of selective Ube3a loss from either GABAergic or glutamatergic
      neurons, focusing on the development of hyperexcitability within L2/3 neocortex
      and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss
      causes AS-like increases in neocortical EEG delta power, enhances seizure
      susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles
      (CCVs)-all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons.
      Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures,
      or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3
      pyramidal neurons. These results substantiate GABAergic Ube3a loss as the
      principal cause of circuit hyperexcitability in AS mice, lending insight into
      ictogenic mechanisms in AS. 

PMID- 27021171
TI  - Cooperative Subnetworks of Molecularly Similar Interneurons in Mouse Neocortex.
AB  - Simultaneous co-activation of neocortical neurons is likely critical for brain
      computations ranging from perception and motor control to memory and cognition.
      While co-activation of excitatory principal cells (PCs) during ongoing activity
      has been extensively studied, that of inhibitory interneurons (INs) has received
      little attention. Here, we show in vivo and in vitro that members of two non
      overlapping neocortical IN populations, expressing somatostatin (SOM) or
      vasoactive intestinal peptide (VIP), are active as populations rather than
      individually. We demonstrate a variety of synergistic mechanisms, involving
      population-specific local excitation, GABAergic disinhibition and excitation
      through electrical coupling, which likely underlie IN population co-activity.
      Firing of a few SOM or VIP INs recruits additional members within the cell type
      via GABAergic and cholinergic mechanisms, thereby amplifying the output of the
      population as a whole. Our data suggest that IN populations work as cooperative
      units, thus generating an amplifying nonlinearity in their circuit output. 

PMID- 27021172
TI  - Cell-Targeted Optogenetics and Electrical Microstimulation Reveal the Primate
      Koniocellular Projection to Supra-granular Visual Cortex.
AB  - Electrical microstimulation and more recently optogenetics are widely used to map
      large-scale brain circuits. However, the neuronal specificity achieved with both
      methods is not well understood. Here we compare cell-targeted optogenetics and
      electrical microstimulation in the macaque monkey brain to functionally map the
      koniocellular lateral geniculate nucleus (LGN) projection to primary visual
      cortex (V1). Selective activation of the LGN konio neurons with CamK-specific
      optogenetics caused selective electrical current inflow in the supra-granular
      layers of V1. Electrical microstimulation targeted at LGN konio layers revealed
      the same supra-granular V1 activation pattern as the one elicited by
      optogenetics. Taken together, these findings establish a selective koniocellular
      LGN influence on V1 supra-granular layers, and they indicate comparable
      capacities of both stimulation methods to isolate thalamo-cortical circuits in
      the primate brain. 

PMID- 27021173
TI  - Millisecond Coupling of Local Field Potentials to Synaptic Currents in the Awake
      Visual Cortex.
AB  - The cortical local field potential (LFP) is a common measure of population
      activity, but its relationship to synaptic activity in individual neurons is not
      fully established. This relationship has been typically studied during anesthesia
      and is obscured by shared slow fluctuations. Here, we used patch-clamp recordings
      in visual cortex of anesthetized and awake mice to measure intracellular
      activity; we then applied a simple method to reveal its coupling to the
      simultaneously recorded LFP. LFP predicted membrane potential as accurately as
      synaptic currents, indicating a major role for synaptic currents in the
      relationship between cortical LFP and intracellular activity. During anesthesia,
      cortical LFP predicted excitation far better than inhibition; during wakefulness,
      it predicted them equally well, and visual stimulation further enhanced
      predictions of inhibition. These findings reveal a central role for synaptic
      currents, and especially inhibition, in the relationship between the subthreshold
      activity of individual neurons and the cortical LFP during wakefulness. 

PMID- 27021174
TI  - Remifentanil Compared With Sufentanil Does Not Enhance Fast-Track Possibilities
      in Cardiac Surgery-A Randomized Study.
AB  - OBJECTIVE: Progressive cost containment has resulted in a growing interest for
      fast-track cardiac surgery. Ventilation time and length of stay (LOS) in the
      intensive care unit (ICU) are important factors in patient turnover, a more
      efficient use of resources, and early patient mobilization. However, LOS in ICU
      is not an objective measure because, in addition to medical factors, patient
      discharge may be guided by logistics and policy, and thus more objective measures
      are warranted. The authors hypothesized that remifentanil compared with
      sufentanil would reduce ventilation time and LOS in the ICU and that remifentanil
      would have beneficial effects on the overall quality of recovery. DESIGN: A
      randomized, prospective study. PARTICIPANTS: Sixty patients scheduled for
      elective coronary artery bypass grafting with or without aortic valve
      replacement. SETTING: A university hospital. INTERVENTIONS: Patients were
      assigned randomly to receive either remifentanil or sufentanil combined with
      propofol. MEASUREMENTS AND MAIN RESULTS: Patients with ejection fraction<0.3,
      myocardial infarction within the last 4 weeks, diabetes, and severe pulmonary or
      arterial hypertension were excluded. The primary outcome variables were
      ventilation time and time to eligibility of discharge from the cardiac recovery
      unit. Secondary outcomes were actual LOS in the cardiac recovery unit and quality
      of recovery. The groups were comparable in selected demographics and
      perioperative parameters. There were no differences in ventilation time or
      eligible ICU discharge time between the groups. Remifentanil patients received
      more morphine than did the sufentanil patients during recovery (20 mg v 10 mg; p
      = 0.040). No difference was found in pharmacologic support or use of a pacemaker.
      CONCLUSION: In a fast-track protocol, remifentanil did not seem to be superior to
      a standard moderate- to high-dose sufentanil regimen.

PMID- 27021175
TI  - Descending Aortic Stent Graft Collapse During Frozen Elephant Trunk Repair:
      Detection Using Invasive Blood Pressure Monitoring and Intraoperative
      Transesophageal Echocardiography.

PMID- 27021176
TI  - Ambulatory Medical Follow-Up in the Year After Surgery and Subsequent Survival in
      a National Cohort of Veterans Health Administration Surgical Patients.
AB  - OBJECTIVES: Among a national cohort of surgical patients, the authors analyzed
      the association between medical follow-up during the first postsurgical year and
      survival during the second postsurgical year. DESIGN: Retrospective cohort study.
      SETTING: US Veterans Hospitals. PARTICIPANTS: The study included adults who
      received surgical care in any Veterans Health Administration facility from 2006
      to 2011 who were discharged within 10 days of surgery and who survived for at
      least 1 year postoperatively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      The association between the receipt of nonsurgical ambulatory medical care during
      the first postoperative year and the hazard of death during postsurgical year 2
      was measured. Among 236,200 veterans, 93.2% received a nonsurgical medical follow
      up visit in postsurgical year 1; of those, 5.1% died during postsurgical year 2.
      This compares with 9.4% year-2 mortality among patients lacking year-1 medical
      follow-up (p<0.0001). After adjustment for confounders, medical follow-up in
      postoperative year 1 again was associated with a significantly lower hazard of
      death in postoperative year 2 (hazard ratio 0.71; 95% confidence interval 0.66
      0.78). Sensitivity analyses examining patient subgroups stratified by procedural
      specialty demonstrated comparable findings. The results were robust under a
      variety of simulated scenarios of unmeasured confounding. CONCLUSIONS: Within a
      national cohort of US veterans who presented for surgery, those who received
      nonsurgical ambulatory follow-up during the first postoperative year demonstrated
      lower all-cause mortality in the subsequent postoperative year than those who did
      not receive the same type of follow-up care. Interventions focused on
      postoperative care coordination of outpatient medical follow-up may have the
      potential to improve long-term postoperative survival.

PMID- 27021177
TI  - CASE 5-2016Complex Congenital Cardiac Surgery in an Adult Patient With Hereditary
      Spherocytosis: Avoidance of Massive Hemolysis Associated With Extracorporeal
      Circulation in the Presence of Red Blood Cell Fragility.

PMID- 27021178
TI  - Transcatheter Aortic Valve Replacement: Recent Evidence from Pivotal Trials.

PMID- 27021179
TI  - Ultrastructural description of Myxobolus cuneus (Myxosporea) in the skeletal
      muscle and kidney of tropical farmed fish Piaractus mesopotamicus (Characiformes:
      Characidae).
AB  - This study characterizes by transmission electron microscopy (TEM) and
      morphometric features the myxozoan Myxobolus cuneus (Myxosporea) in Piaractus
      mesopotamicus and reports the skeletal muscle and kidney as site of infection.
      The register was based in 21 young fish from intensive fish farming in Southeast
      Brazil and the spores were analyzed in fresh-mounted slides of the infected
      organs stained with Toluidine blue and processed as usual for TEM. It differs
      from Myxobolus cunhai from the fish host and different polar capsule size, and
      from Myxobolus serrasalmi on the pyriform spore shape and an oval macrospore,
      differently to that reported in this study. Morphometric characteristics and TEM
      study confirmed the present material as M. cuneus. 

PMID- 27021180
TI  - The complete mitochondrial genome of Gastrothylax crumenifer (Gastrothylacidae,
      Trematoda) and comparative analyses with selected trematodes.
AB  - In the present study, we sequenced and analyzed the mitochondrial (mt) genome of
      Gastrothylax crumenifer and compared it with other selected trematodes. The full
      mt genome of G. crumenifer was amplified, sequenced, assembled, analyzed and then
      subjected to phylogenetic analysis. The complete mt genome of G. crumenifer is
      14,801 bp in length and contains two rRNA genes, two non-coding regions (LNR and
      SNR), 12 protein-coding genes, and 22 transfer RNA genes. The gene organization
      of the G. crumenifer mt genome is the same as that of other trematodes, except
      for Schistosoma haematobium and Schistosoma spindale. All the genes are
      transcribed in the same direction and rich in "A + T", which is in accordance
      with other trematodes, such as Fasciola hepatica, Paramphistomum cervi, and
      Fischoederius elongatus. Phylogenetic analysis using concatenated amino acid
      sequences of the 12 protein-coding genes showed that G. crumenifer is closely
      related to F. elongatus. The availability of mt genome sequence of G. crumenifer
      can provide useful DNA markers for studying the molecular epidemiology and
      population genetics of this parasite and other paramphistomes. 

PMID- 27021181
TI  - Identification and characterization of microRNAs in the zoonotic fluke
      Fasciolopsis buski.
AB  - Fasciolopsis buski is a food-borne zoonotic parasite which is transmitted by
      aquatic plants, with pigs and humans as the definitive hosts. The objective of
      the present study was to characterize the microRNA (miRNA) profiles of this
      parasite by Solexa deep sequencing and bioinformatic analysis. Approximately 12
      million high-quality reads were obtained from adult F. buski. A total of 286
      miRNA candidates were found and 24 miRNA candidates were conserved miRNAs in the
      miRBase database. Three novel miRNAs were identified and confirmed by stem-loop
      reverse transcriptase polymerase chain reaction (RT-PCR). The miRNAs found in the
      present study belong to 13 families whose members showed high bias. The guanine
      (G) was the dominant nucleotide at the beginning and middle of the conserved
      miRNAs, particularly at the positions of 2nd, 6th, and 13th. To our knowledge,
      this is the first report of the miRNA profiles of F. buski, which would lay a
      foundation for further functional studies of miRNAs of F. buski. 

PMID- 27021182
TI  - Toxoplasma gondii ROP18: potential to manipulate host cell mitochondrial
      apoptosis.
AB  - Toxoplasma gondii is an obligate intracellular parasite that may manipulate host
      cell mitochondrial apoptosis pathways. In our experiment, 293T cells were
      transfected with the p3*FLAG-CMV-Myc-ROP18 vector and expressed the ROP18-Myc
      fusion protein. Cell apoptosis was induced by 0.5 MUg/mL actinomycin D (ActD) and
      was detected by Annexin V-FITC/PI assay. The cell mitochondrial membrane
      potential was determined by JC-1. Cytochrome c (Cyto-c) from mitochondria and the
      cytoplasm was measured by Western blot. The Bcl-2 and Bax coding gene expression
      levels were detected by real-time PCR. We found, in vitro, that T. gondii ROP18
      significantly suppressed 293T cell apoptosis induced by ActD and maintained
      mitochondrial membrane potential and integrity, thereby preventing the release of
      Cyto-c from mitochondria into the cytoplasm. The ratio of Bcl-2/Bax in ROP18
      overexpressing cells was significantly higher than that of the negative control.
      Therefore, we speculate that ROP18 could suppress host cell apoptosis via the
      mitochondrial apoptosis pathway in vitro. 

PMID- 27021183
TI  - Molecular differentiation of bovine sarcocysts.
AB  - Cattle are common intermediate hosts of Sarcocystis, and the prevalence in adult
      bovine muscle is close to 100 % in most regions of the world. Three Sarcocystis
      spp. are known to infect cattle as intermediate hosts, namely, S. cruzi, S.
      hirsuta, and S. hominis. The aim of the present study was the molecular
      identification and differentiation of these three species, Neospora caninum and
      Besnoitia by PCR and RFLP methods. Tissue samples were obtained from
      diaphragmatic muscle of 101 cattle slaughtered in Shiraz, Fars Province, Iran,
      for both smear preparation and DNA extraction. The samples were digested by
      Pepsin, washed three times with PBS solution before taking smears, fixed in
      absolute methanol and stained with 10 % Giemsa. The slides were examined
      microscopically for Sarcocystis bradyzoites and DNA was extracted from 100 mg of
      Sarcocystis-infected meat samples. Since the primers also bind to 18S rRNA gene
      of some tissue cyst-forming coccidian protozoa, DNA was also extracted from 100
      MUl of tachyzoite-containing suspension of N. caninum and Besnoitia isolated from
      goat to compare RFLP pattern. Polymerase chain reaction (PCR) was performed on
      DNA of samples which were microscopically positive for Sarcocystis. Five
      restriction enzymes Dra1, EcoRV, RsaI, AvaI, and SspI were used for RFLP and DNA
      of one sample from protozoa was sequenced. Based on the RFLP results, 87 (98.9 %)
      DNA samples were cut with DraI, indicating infection by S. cruzi. One sample (1.1
      %) of PCR products of infected samples was cut only with EcoRV which showed S.
      hominis infection. Forty-eight samples (53.3 %) of PCR products were cut with
      both DraI, EcoRV, or with DraI, EcoRV, and RsaI while none of them was cut with
      SspI, which shows the mixed infection of both S. cruzi and S. hominis and no
      infection with S. hirsuta. It seems by utilizing these restriction enzymes, RLFP
      could be a suitable method not only for identification of Sarcocystis species but
      also for differentiating them from N. caninum and Besnoitia. 

PMID- 27021184
TI  - Surface histology, topography, and ultrastructure of the tegument of adult
      Orthocoelium parvipapillatum (Stiles & Goldberger, 1910).
AB  - Adult Orthocoelium parvipapillatum are common parasites that reside in the rumen
      and reticulum of ruminants, i.e., cattle, sheep, goats, and buffaloes. The fluke
      is conical-shaped and slightly concave ventrally and convex dorsally, and
      measures bout 2.4-3.9 mm in length and 1.0-2.3 mm in width across the mid
      section. The tegument of the adult worm is examined using light microscopy (LM)
      and scanning (SEM) and transmission electron microscopy (TEM). Under LM, the
      tegument appears as a thick homogeneous layer containing folds alternated with
      grooves without spines. SEM revealed that the tegumental surface is highly
      corrugated with ridges and furrows and appears spineless. Two types of sensory
      papillae are observed, i.e., type 1 is bulbous in shape with nipple-like tips and
      type 2 has a similar shape with short cilia. In TEM, the tegument has a typical
      syncytial organization and is divided into four layers. The first layer of the
      tegument contains ridges and furrows covered by a trilaminate membrane coated
      externally with the glycocalyx. The second layer is a strait area of cytoplasm
      that includes numerous ovoid electron-lucent (TG1) and disc-shaped electron-dense
      (TG2) tegumental granules and lysosomes. The third layer is the widest middle
      area which contains several evenly distributed mitochondria, TG1 and TG2. The
      fourth layer rests on a thick basal lamina and contains numerous infoldings of
      the basal plasma membrane with closely associated mitochondria. Both granules are
      produced and transported to the tegument by one type of tegumental cells lying in
      rows below the muscular layers. 

PMID- 27021185
TI  - Canine dirofilariosis endemic in Central Europe-10 years of epidemiological study
      in Slovakia.
AB  - The study presents the comprehensive results of a detailed epidemiological study
      on canine dirofilariosis in Slovakia, Central Europe. More than 4000 dogs were
      investigated, and several epidemiological factors were considered. The mean
      prevalence in individual regions ranged from 2.0 % in northern Slovakia to more
      than 25.0 % in the south-western part of the country, with the nematode
      Dirofilaria repens confirmed as the dominant causative agent. Canine
      dirofilariosis occurred more often in animals more than 3 years old and in dogs
      of large and giant breed sizes. Short-haired animals were infected more often
      than dogs with a long coat. Also, the infection was significantly more prevalent
      in animals kept in rural areas in comparison with urban environments.Counts of
      microfilariae (mf) in peripheral blood reached their highest levels in May and
      August and corresponded to activity peaks and population maximums of potential
      vectors, the mosquito species Aedes vexans and Culex pipiens, the two most
      prevalent species in Slovakia. Moreover, two dogs naturally infested with D.
      repens were included in the experiment in order to monitor daily microfilarial
      periodicity. This fluctuation showed the same tendency in both animals, with a
      peak of circulating mf recorded at 4 a.m. and minimal mf counts at 4 p.m. 

PMID- 27021186
TI  - Molecular characterization of Echinococcus granulosus sensu stricto and
      Echinococcus canadensis in humans and livestock from Algeria.
AB  - In Algeria, previous studies investigated genotypes of Echinococcus granulosus
      sensu lato in animals and identified E. granulosus sensu stricto (s.s.) genotypes
      G1 and G3 whereas Echinococcus canadensis genotype G6 was only reported from
      dromedary cysts. Molecular data on human cystic echinococcosis (CE) were limited.
      We implemented a large genotyping study of hydatid cysts from humans and
      livestock animals to specify CE's molecular epidemiology and the genetic
      diversity in Algeria. Fifty-four human CE cysts from patients predominantly
      admitted in surgical units from Mustapha Hospital, Algiers, and 16 cysts from
      livestock animals gathered in two geographically distinct slaughterhouses, Tiaret
      and Tamanrasset, were collected. Molecular characterization was performed using
      sequencing of two mitochondrial genes, cytochrome c oxidase subunit I (COI) and
      NADH dehydrogenase subunit I (NDI). In humans, G1 of E. granulosus s.s. was the
      main genotype (90.7 %); four samples (7.4 %) were characterized as E. granulosus
      s.s. G3 and one cyst as E. canadensis G6 (1.8 %). This molecular confirmation of
      E. canadensis G6 human infection in Algeria was observed in a Tuareg female
      living in a desertic area in Tamanrasset. All cysts from sheep, cattle, and goat
      were identified as E. granulosus s.s. G1 and the two cysts originating from
      dromedary as E. canadensis G6. Twenty concatenated haplotypes (COI + NDI) were
      characterized. Among E. granulosus s.s., one haplotype (HL1) was highly
      predominant in both humans and animals cysts (71.6 %). This study revealed main
      occurrence of E. granulosus s.s. in humans and livestock animals, with
      description of a predominant shared haplotype corresponding to the main worldwide
      observed haplotype E.granulosus s.s. G1. E. canadensis G6 was limited to South
      Algeria, in dromedary as well as in human. 

PMID- 27021187
TI  - Erratum to: "Trans-stent B-mode Ultrasound and Passive Cavitation Imaging" in
      Ultrasound Med Biol 2016;42(2):518-527.

PMID- 27021188
TI  - A Formate Dehydrogenase Confers Tolerance to Aluminum and Low pH.
AB  - Formate dehydrogenase (FDH) is involved in various higher plant abiotic stress
      responses. Here, we investigated the role of rice bean (Vigna umbellata) VuFDH in
      Al and low pH (H(+)) tolerance. Screening of various potential substrates for the
      VuFDH protein demonstrated that it functions as a formate dehydrogenase.
      Quantitative reverse transcription-PCR and histochemical analysis showed that the
      expression of VuFDH is induced in rice bean root tips by Al or H(+) stresses.
      Fluorescence microscopic observation of VuFDH-GFP in transgenic Arabidopsis
      plants indicated that VuFDH is localized in the mitochondria. Accumulation of
      formate is induced by Al and H(+) stress in rice bean root tips, and exogenous
      application of formate increases internal formate content that results in the
      inhibition of root elongation and induction of VuFDH expression, suggesting that
      formate accumulation is involved in both H(+)- and Al-induced root growth
      inhibition. Over-expression of VuFDH in tobacco (Nicotiana tabacum) results in
      decreased sensitivity to Al and H(+) stress due to less production of formate in
      the transgenic tobacco lines under Al and H(+) stresses. Moreover, NtMATE and
      NtALS3 expression showed no changes versus wild type in these over-expression
      lines, suggesting that herein known Al-resistant mechanisms are not involved.
      Thus, the increased Al tolerance of VuFDH over-expression lines is likely
      attributable to their decreased Al-induced formate production. Taken together,
      our findings advance understanding of higher plant Al toxicity mechanisms, and
      suggest a possible new route toward the improvement of plant performance in
      acidic soils, where Al toxicity and H(+) stress coexist.

PMID- 27021189
TI  - The Roles of Mitochondrial Reactive Oxygen Species in Cellular Signaling and
      Stress Response in Plants.
AB  - Mitochondria produce ATP via respiratory oxidation of organic acids and transfer
      of electrons to O2 via the mitochondrial electron transport chain. This process
      produces reactive oxygen species (ROS) at various rates that can impact
      respiratory and cellular function, affecting a variety of signaling processes in
      the cell. Roles in redox signaling, retrograde signaling, plant hormone action,
      programmed cell death, and defense against pathogens have been attributed to ROS
      generated in plant mitochondria (mtROS). The shortcomings of the black box-idea
      of mtROS are discussed in the context of mechanistic considerations and the
      measurement of mtROS The overall aim of this update is to better define our
      current understanding of mtROS and appraise their potential influence on cellular
      function in plants. Furthermore, directions for future research are provided,
      along with suggestions to increase reliability of mtROS measurements.

PMID- 27021191
TI  - Prospective Study of Glycemic Load, Glycemic Index, and Carbohydrate Intake in
      Relation to Risk of Biliary Tract Cancer.
AB  - OBJECTIVES: Diets that induce a high glycemic response might increase the risk of
      biliary tract cancer (BTC). We evaluated the hypothesis that diets with high
      glycemic load (GL) and high glycemic index (GI), which are measures of the
      glycemic effect of foods, are associated with an increased incidence of BTC.
      METHODS: We used data from a population-based prospective study of 76,014 Swedish
      adults (age 45-83 years; 57% men) who were free of cancer and had completed a
      food-frequency questionnaire in the autumn of 1997. Incident cancer cases were
      ascertained by linkage with the Swedish Cancer Registry. Data were analyzed using
      Cox proportional hazards regression models. RESULTS: During a mean follow-up of
      13.3 years (1,010,777 person-years), we identified 140 extrahepatic BTC cases
      (including 77 gallbladder cancers) and 23 intrahepatic BTC cases. A high dietary
      GL was associated with an increased risk of BTC. The multivariable relative risks
      for the highest versus lowest quartile of dietary GL were 1.63 (95% confidence
      interval (95% CI), 1.01-2.63) for extrahepatic BTC, 2.14 (95% CI, 1.06-4.33) for
      gallbladder cancer, and 3.46 (95% CI, 1.22-9.84) for intrahepatic BTC. Dietary GI
      was statistically significantly positively associated with risk of extrahepatic
      BTC and gallbladder cancer. We observed no statistically significant association
      between carbohydrate intake and BTC risk, although all associations were
      positive. CONCLUSION: Although these data do not prove a causal relationship,
      they are consistent with the hypothesis that high-GL and high-GI diets are
      associated with an increased risk of BTC.

PMID- 27021190
TI  - MtSWEET11, a Nodule-Specific Sucrose Transporter of Medicago truncatula.
AB  - Optimization of nitrogen fixation by rhizobia in legumes is a key area of
      research for sustainable agriculture. Symbiotic nitrogen fixation (SNF) occurs in
      specialized organs called nodules and depends on a steady supply of carbon to
      both plant and bacterial cells. Here we report the functional characterization of
      a nodule-specific Suc transporter, MtSWEET11 from Medicago truncatula MtSWEET11
      belongs to a clade of plant SWEET proteins that are capable of transporting Suc
      and play critical roles in pathogen susceptibility. When expressed in mammalian
      cells, MtSWEET11 transported sucrose (Suc) but not glucose (Glc). The MtSWEET11
      gene was found to be expressed in infected root hair cells, and in the meristem,
      invasion zone, and vasculature of nodules. Expression of an MtSWEET11-GFP fusion
      protein in nodules resulted in green fluorescence associated with the plasma
      membrane of uninfected cells and infection thread and symbiosome membranes of
      infected cells. Two independent Tnt1-insertion sweet11 mutants were uncompromised
      in SNF Therefore, although MtSWEET11 appears to be involved in Suc distribution
      within nodules, it is not crucial for SNF, probably because other Suc
      transporters can fulfill its role(s).

PMID- 27021192
TI  - An Unexpected Turn: My Life as a Cancer Advocate.

PMID- 27021194
TI  - Impact of Endotracheal Intubation on Interventional Endoscopy Unit Efficiency
      Metrics at a Tertiary Academic Medical Center.
AB  - OBJECTIVES: Measures for evaluating interventional endoscopy unit efficiency have
      not been adequately validated, especially in reference to the involvement of
      anesthesia services for endoscopy. Primary aim was to compare process
      measures/metrics of interventional endoscopy unit efficiency between intubated
      and non-intubated patients. Secondary aim was to assess variables associated with
      the need for endotracheal intubation. METHODS: The prospectively collected
      endoscopy unit metrics database at UF Health was reviewed for procedures
      performed in the interventional endoscopy unit for 6 months. Parameters included
      hospital-mandated metrics available from the database. RESULTS: A total of 1,421
      patients underwent 1,635 interventional endoscopic procedures and 271/1,421
      patients (19.1%) were intubated. There was no significant difference between
      intubated and non-intubated cohorts with respect to age, gender, BMI, ASA Score,
      Mallampati Score, or the Charlson Comorbidity Index. Patients undergoing
      endoscopic retrograde cholangiopancreatography (ERCP) were more frequently
      intubated than those undergoing non-ERCP procedures (41.3 vs. 12.4%, P<0.0001).
      Inpatients comprised 48.3% of all intubated patients, whereas only 29.2% of non
      intubated patients were inpatients (P<0.0001). Most patients (159/271, 58.7%)
      were intubated per anesthesiologist preference. All process efficiency metrics
      were significantly prolonged in the intubated compared with the non-intubated
      patient cohort, except the time interval between successive procedures.
      Multivariate analysis revealed that patients with an anesthesiologist who had
      performed a greater number of total endoscopic sedations were less likely to be
      intubated than patients with an anesthesiologist who had performed fewer total
      procedures (P=0.0066). CONCLUSIONS: Endotracheal intubation negatively impacts
      efficiency metrics in an interventional endoscopy unit. Careful assessment for
      the need for intubation should be emphasized.

PMID- 27021193
TI  - CT-Colonography vs. Colonoscopy for Detection of High-Risk Sessile Serrated
      Polyps.
AB  - OBJECTIVES: Sessile serrated polyps (SSPs) are suggested to be the precursors of
      15-30% of all colorectal cancers (CRCs). Therefore, CRC screening modalities
      should also be designed to detect high-risk SSPs. We compared computed tomography
      colonography (CTC) with colonoscopy-based screening for the detection of high
      risk SSPs in average-risk individuals. METHODS: Data from a randomized controlled
      trial that compared CTC with colonoscopy for population screening were used for
      the analysis. Individuals diagnosed at CTC with a lesion >=10 mm in size were
      referred for colonoscopy. Individuals with only 6-9 mm lesions were offered
      surveillance CTC. This surveillance CTC was followed by a colonoscopy when a
      lesion >=6 mm was detected. Yield of both was accumulated to mimic current
      American College of Radiology CTC referral strategy (referral of individuals with
      any lesion >=6 mm). Per participant detection of >=1 high-risk (dysplastic and/or
      >=10 mm) SSP was compared with colonoscopy using multiple logistic regression
      analysis. RESULTS: In total, 8,844 individuals were invited to participate (in
      2:1 allocation), of which 1,276 colonoscopy and 982 CTC invitees participated in
      the study. In the colonoscopy arm, 4.3% of individuals were diagnosed with >=1
      high-risk SSP, compared with 0.8% in the CTC arm (odds ratio (OR) 5.5; 95%
      confidence interval (CI) 2.6-11.6; P<0.001). In total, 3.1% of individuals in the
      colonoscopy arm were diagnosed with high-risk SSPs as most advanced lesion,
      compared with 0.4% in the CTC arm (OR 7.7; 95% CI 2.7-21.6; P<0.001). The current
      CTC strategy showed a marked lower detection for especially flat high-risk SSPs
      (17 vs. 0), high-risk SSP located in the proximal colon (32 vs. 1), and SSPs with
      dysplasia (30 vs. 1). CONCLUSIONS: In a randomized controlled setting, the
      detection rate of high-risk SSPs was significantly higher with colonoscopy than
      CTC. These results might have implications for CTC as a CRC modality for
      opportunistic screening in average-risk adults.

PMID- 27021195
TI  - Screening for Cancer Genetic Syndromes With a Simple Risk-Assessment Tool in a
      Community-Based Open-Access Colonoscopy Practice.

PMID- 27021196
TI  - Current Status of Celiac Disease Drug Development.
AB  - Celiac disease (CeD) is one of the most common immune-mediated diseases. Symptoms
      and disease activity are incompletely controlled by the gluten-free diet, which
      is currently the only available therapy. Although no therapies are yet approved,
      there is a growing field of candidates and an improving understanding of the
      regulatory pathway. In this review, we briefly discuss the epidemiology,
      pathophysiology, and current treatment paradigm for CeD. We also review the major
      classes of therapies being considered for CeD and discuss extensively what is
      known and can be surmised regarding the regulatory pathway for approval of a CeD
      therapeutic. The coming years will see an increasing number and diversity of
      potential therapies entering clinical trials and hopefully the first approved
      agents targeting this significant unmet medical need. Although biomarkers
      including histology and serology will always be important in therapeutic clinical
      trials, they currently lack the necessary evidence linking them to improved
      patient outcomes required for use as primary outcomes for drug approval. For this
      reason, patient-reported outcomes will likely be primary end points in Phase III
      CeD trials for the foreseeable future.

PMID- 27021197
TI  - An In-Depth Analysis of Patient-Reported Outcomes in Patients With Chronic
      Hepatitis C Treated With Different Anti-Viral Regimens.
AB  - OBJECTIVES: Interferon- and ribavirin (RBV)-containing regimens negatively impact
      patients' experience. The aim of this study was to quantify the impact of
      different anti-viral regimens for hepatitis C on patients' work productivity,
      fatigue, and other patient-reported outcomes (PROs). METHODS: The PRO data from
      multicenter multinational phase 3 clinical trials of sofosbuvir with and without
      interferon or RBV were retrospectively used. Treatment regimens were classified
      as interferon+RBV-containing, interferon-free RBV-containing, and interferon-free
      RBV-free. Four PRO instruments (SF-36, CLDQ-HCV, FACIT-F, and WPAI:SHP) were
      administered to subjects at baseline, during, and up to 24 weeks after treatment.
      RESULTS: We included 3,425 subjects with chronic hepatitis C infection with PRO
      data. Patients were 62.8% male, 62.2% treatment naive, 18.1% with cirrhosis, and
      72.9% with HCV genotype 1. Of the study participants, 546 received
      interferon+RBV+sofosbuvir, 1,721 received sofosbuvir+RBV, and 1,158 received
      interferon- and RBV-free ledipasvir+sofosbuvir. At baseline, there were no
      difference in PROs between treatment groups (all P>0.01). During treatment, the
      decrements in PROs were up to -23.6% for the interferon+RBV group, up to -7.0% in
      the sofosbuvir+RBV group, whereas there was an improvement of up to +11.6% in the
      interferon-free RBV-free group (all P<0.0001). In multivariate analysis, the use
      of interferon was independently associated with up to -26.0% worsening of the PRO
      scores during treatment and the use of RBV with up to -9.0% worsening. After 12
      weeks post-treatment, in patients with sustained virologic response-12,
      improvements were observed regardless of the regimen, and these improvements
      continued to increase by week 24 of follow-up. CONCLUSIONS: The use of interferon
      and RBV-free regimens for HCV is associated with better patients' experience and
      work productivity during treatment.

PMID- 27021198
TI  - Functional Bowel Disorders: A Patient's Perspective.

PMID- 27021199
TI  - Access to Subspecialty Care And Survival Among Patients With Liver Disease.
AB  - OBJECTIVES: Access to subspecialty care may be difficult for patients with liver
      disease, but it is unknown whether access influences outcomes among this
      population. Our objectives were to determine rates and predictors of access to
      ambulatory gastrointestinal (GI) subspecialty care for patients with liver
      disease and to determine whether access to subspecialty GI care is associated
      with better survival. METHODS: We studied 28,861 patients within the Veterans
      Administration VISN 11 Liver Disease cohort who had an ICD-9-CM diagnosis code
      for liver disease from 1 January 2000 through 30 May 2011. Access was defined as
      a completed outpatient clinic visit with a gastroenterologist or hepatologist at
      any time after diagnosis. Multivariable logistic regression was used to determine
      predictors of access to a GI subspecialist. Survival curves were compared between
      those who did and those who did not see a specialist, with propensity score
      adjustment to account for other covariates that may affect access. RESULTS:
      Overall, 10,710 patients (37%) had a completed GI visit. On multivariable
      regression, older patients (odds ratio (OR) 0.98, P<0.001), those with more
      comorbidities (OR 0.98, P=0.01), and those living farther from a tertiary-care
      center (OR 0.998/mi, P<0.001) were less likely to be seen in clinic. Patients who
      were more likely to be seen included those who had hepatitis C (OR 1.5, P<0.001)
      or cirrhosis (OR 3.5, P<0.001) diagnoses prior to their initial visit. Patients
      with an ambulatory GI visit at any time after diagnosis were less likely to die
      at 5 years when compared with propensity-score-matched controls (hazard ratio
      0.81, P<0.001). CONCLUSIONS: Access to ambulatory GI care was associated with
      improved 5-year survival for patients with liver disease. Innovative care
      coordination techniques may prove beneficial in extending access to care to liver
      disease patients.

PMID- 27021200
TI  - Correction: A Co(2+)-selective and chirality-sensitive supermolecular
      metallohydrogel with a nanofiber network skeleton.
AB  - Correction for 'A Co(2+)-selective and chirality-sensitive supermolecular
      metallohydrogel with a nanofiber network skeleton' by Xiaojuan Wang et al.,
      Nanoscale, 2016, DOI: 10.1039/c6nr00822d. 

PMID- 27021202
TI  - [The vaccination-induced cooperation of T cells and myeloid cells leads to an
      anti-tumoral effect].

PMID- 27021201
TI  - Re-induction of the cell cycle in the Arabidopsis post-embryonic root meristem is
      ABA-insensitive, GA-dependent and repressed by KRP6.
AB  - Seeding establishment following seed germination requires activation of the root
      meristem for primary root growth. We investigated the hormonal and genetic
      regulation of root meristem activation during Arabidopsis seed germination. In
      optimal conditions, radicle cell divisions occur only after the completion of
      germination and require de novo GA synthesis. When the completion of germination
      is blocked by ABA, radicle elongation and cell divisions occurred in these non
      germinating seeds. Conversely under GA-limiting conditions, ABA-insensitive
      mutants complete germination in the absence of radicle meristem activation and
      growth. Radicle meristem activation and extension can therefore occur
      independently of completion of the developmental transition of germination. The
      cell cycle regulator KRP6 partially represses GA-dependent activation of the cell
      cycle. Germination of krp6 mutant seeds occurs more rapidly, is slightly
      insensitive to ABA in dose-response assays, but also hypersensitive to the GA
      synthesis inhibitor PAC. These conflicting phenotypes suggest the cell cycle
      uncouples GA and ABA responses in germinating Arabidopsis seeds, and that KRP6
      acts downstream of GA to inhibit mitotic cell cycle activation during
      germination. 

PMID- 27021203
TI  - Ti3+-self doped brookite TiO2 single-crystalline nanosheets with high solar
      absorption and excellent photocatalytic CO2 reduction.
AB  - Black brookite TiO2 single-crystalline nanosheets with outstanding photocatalytic
      activity toward CO2 reduction is prepared by a facile oxidation-based
      hydrothermal reaction method combined with post-annealing treatment. Large amount
      of Ti(3+) defects are introduced into the bulk of brookite nanoparticles, which
      increases the solar energy absorption and enhances the photocatalytic activity. 

PMID- 27021204
TI  - Anoxygenic Photosynthesis -A Photochemical Reaction That Does Not Contribute to
      Oxygen Reproduction.

PMID- 27021205
TI  - Overview of elagolix for the treatment of endometriosis.
AB  - INTRODUCTION: Suppression of sex-steroid secretion is required in a variety of
      gynecological conditions. This can be achieved using gonadotropin releasing
      hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize
      the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH
      pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal
      steroid levels, avoiding the initial stimulatory phase of the agonists. Potential
      benefits of GnRH antagonists over GnRH agonists include a rapid onset and
      reversibility of action. Older GnRH antagonists are synthetic peptides, obtained
      by modifications of certain amino acids in the native GnRH sequence. They require
      subcutaneous injections, implantation of long-acting depots. The peptide
      structure is responsible for histamine-related adverse events and the tendency to
      elicit hypersensitivity reactions. AREAS COVERED: Research has worked towards the
      development of non-peptidic molecules exerting antagonist action on GnRH. They
      are available for oral administration and may have a more beneficial safety
      profile in comparison with peptide GnRH antagonists. This article focuses on the
      data of the literature about elagolix, a novel non-peptidic GnRHantagonist, in
      the treatment of endometriosis. EXPERT OPINION: Elagolix demonstrated efficacy in
      the management of endometriosis-associated pain and had an acceptable safety and
      tolerability profile. However, further studies are necessary to evaluate its non
      inferiority in comparison with other endometriosis's treatments.

PMID- 27021206
TI  - A systematic review of instruments assessing dimensions of distress among
      caregivers of adult and pediatric cancer patients.
AB  - OBJECTIVE: Caregivers of cancer patients face intense demands throughout the
      course of the disease, survivorship, and bereavement. Caregiver burden, needs,
      satisfaction, quality of life, and other significant areas of caregiving are not
      monitored regularly in the clinic setting, resulting in a need to address the
      availability and clinical effectiveness of cancer caregiver distress tools. This
      review aimed to determine the availability of cancer caregiver instruments, the
      variation of instruments between different domains of distress, and that between
      adult and pediatric cancer patient populations. METHOD: A literature search was
      conducted using various databases from 1937 to 2013. Original articles on
      instruments were extracted separately if not included in the original literature
      search. The instruments were divided into different areas of caregiver distress
      and into adult versus pediatric populations. Psychometric data were also
      evaluated. RESULTS: A total of 5,541 articles were reviewed, and 135 articles
      (2.4%) were accepted based on our inclusion criteria. Some 59 instruments were
      identified, which fell into the following categories: burden (n = 26, 44%);
      satisfaction with healthcare delivery (n = 5, 8.5%); needs (n = 14, 23.7%);
      quality of life (n = 9, 15.3%); and other issues (n = 5, 8.5%). The median number
      of items was 29 (4-125): 20/59 instruments (33.9%) had <=20 items; 13 (22%) had
      <=20 items and were psychometrically sound, with 12 of these 13 (92.3%) being
      self-report questionnaires. There were 44 instruments (74.6%) that measured
      caregiver distress for adult cancer patients and 15 (25.4%) for caregivers of
      pediatric patients. SIGNIFICANCE OF RESULTS: There is a significant number of
      cancer caregiver instruments that are self-reported, concise, and
      psychometrically sound, which makes them attractive for further research into
      their clinical use, outcomes, and effectiveness.

PMID- 27021207
TI  - Acceptance and commitment therapy in youth with neurofibromatosis type 1 (NF1)
      and chronic pain and their parents: A pilot study of feasibility and preliminary
      efficacy.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder
      affecting about 1 in 3,500 individuals. Chronic pain is commonly reported among
      individuals with NF1 and plexiform neurofibroma tumors (PNs). Acceptance and
      Commitment Therapy (ACT), an empirically supported method for addressing chronic
      pain, helps individuals re-focus on valued relationships and activities. This
      pilot study investigated the feasibility and preliminary efficacy of a brief ACT
      workshop in the NF1 population. Eligible participants included adolescents and
      young adults (AYA; 12-21 years) with NF1 and chronic pain that interfered with
      daily functioning and their parents. Patients and parents completed baseline
      measures of pain interference, pain intensity, functional disability, pain
      acceptance, depression, and anxiety. Then, AYA and parents participated
      separately in a 2-day small-group ACT workshop. A telephone booster session
      occurred 1 month post-intervention. Three-month post-treatment measures were
      completed by mail. Ten adolescents (4 males; M age = 16.9 years) and seven
      parents provided baseline and 3-month data. Mean satisfaction with the study was
      moderate to high (3.9 for patients and 4.6 for parents on a 1-5 scales). Patients
      and parents reported significant declines in patients' pain interference at 3
      months post-treatment. Patient-reported pain intensity significantly declined
      from baseline to 3 months. Parents reported marginally greater acceptance of
      their child's pain. No changes emerged in functional ability or mood. Preliminary
      findings suggest that a brief ACT group intervention is feasible and may help AYA
      with NF1 and PNs cope with their chronic pain, although larger randomized studies
      are needed to confirm treatment efficacy. (c) 2016 Wiley Periodicals, Inc.

PMID- 27021208
TI  - Soybean-Derived Isoflavone Determination in Rumen Fluid and Milk by LC-MS-(TOF).
AB  - Soybean-derived isoflavones belong to the family of biologically active
      phytoestrogens. The purpose of this study was to develop a sensitive method,
      which permits quantification of the soybean isoflavonoids and equol in bovine
      rumen fluid and milk using LC-MS-(TOF). The samples of rumen fluid and milk were
      obtained from 12 lactating dairy cows ingesting 7,500-9,500 mg of total
      isoflavones daily. The validation of the developed method showed the limits of
      quantification to be in the range of 0.9-5.0 ng/mL. The precision was determined
      as relative standard deviation, which was lower than 25% in all cases. The
      recoveries of the most isoflavonoids were satisfactory. Lower recoveries of
      daidzin and glycitin can be solved by adding an internal standard. The presented
      method will be useful for kinetic studies of isoflavone metabolism in ruminants
      due to simultaneous quantification of free aglycones and glycosides in the rumen
      fluid. 

PMID- 27021209
TI  - Homology modeling, docking, and molecular dynamics simulation of the receptor
      GALR2 and its interactions with galanin and a positive allosteric modulator.
AB  - Galanin receptor type 2 (GALR2) is a class A G-protein-coupled receptor (GPCR),
      and it has been reported that orthosteric ligands and positive allosteric
      modulators (PAMs) of GALR2 could potentially be used to treat epilepsy. So far,
      the X-ray structure of this receptor has not been resolved, and knowledge of the
      3D structure of GALR2 may prove informative in attempts to design novel ligands
      and to explore the mechanism for the allosteric modulation of this receptor. In
      this study, homology modeling was used to obtain several GALR2 models using known
      templates. ProSA-web Z-scores and Ramachandran plots as well as pre-screening
      against a test dataset of known compounds were all utilized to select the best
      model of GALR2. Molecular dockings of galanin (a peptide) and a nonpeptide ligand
      were carried out to choose the (GALR2 model)-galanin complex that showed the
      closest agreement with the corresponding experimental data. Finally, a 50-ns MD
      simulation was performed to study the interactions between the GALR2 model and
      the synthetic and endogenous ligands. The results from docking and MD simulation
      showed that, besides the reported residues, Tyr160(4.60), Ile105(3.32),
      Ala274(7.35), and Tyr163(ECL2) also appear to play important roles in the binding
      of galanin. The potential allosteric binding pockets in the GALR2 model were then
      investigated via MD simulation. The results indicated that the mechanism for the
      allosteric modulation caused by PAMs is the binding of the PAM at pocket III,
      which is formed by galanin, ECL2, TM2, TM3, and ECL1; this results in the
      disruption of the Na(+)-binding site and/or the Na(+) ion pathway, leading to
      GALR2 agonism. 

PMID- 27021210
TI  - Impacts of the charged residues mutation S48E/N62H on the thermostability and
      unfolding behavior of cold shock protein: insights from molecular dynamics
      simulation with Go model.
AB  - The cold shock protein from the hyperthermophile Thermotoga maritima (Tm-Csp)
      exhibits significantly higher thermostability than its homologue from the
      thermophile Bacillus caldolyticus (Bc-Csp). Experimental studies have shown that
      the electrostatic interactions unique to Tm-Csp are responsible for improving its
      thermostability. In the present work, the favorable charged residues in Tm-Csp
      were grafted into Bc-Csp by a double point mutation of S48E/N62H, and the impacts
      of the mutation on the thermostability and unfolding/folding behavior of Bc-Csp
      were then investigated by using a modified Go model, in which the electrostatic
      interactions between charged residues were considered in the model. Our
      simulation results show that this Tm-Csp-like charged residue mutation can
      effectively improve the thermostability of Bc-Csp without changing its two-state
      folding mechanism. Besides that, we also studied the unfolding kinetics and
      unfolding/folding pathway of the wild-type Bc-Csp and its mutant. It is found
      that this charged residue mutation obviously enhanced the stability of the C
      terminal region of Bc-Csp, which decreases the unfolding rate and changes the
      unfolding/folding pathway of the protein. Our studies indicate that the
      thermostability, unfolding kinetics and unfolding/folding pathway of Bc-Csp can
      be artificially changed by introducing Tm-Csp-like favorable electrostatic
      interactions into Bc-Csp.

PMID- 27021211
TI  - Investigation of the effect of erythrosine B on amyloid beta peptide using
      molecular modeling.
AB  - Neurotoxic plaques composed of 39 to 42 residue-long amyloid beta peptides
      (Abetas) are copiously present in the brains of patients with Alzheimer's disease
      (AD). Erythrosine B (ER), a xanthene food dye, inhibits the formation of Abeta
      fibrils and Abeta-associated cytotoxicity in vitro. Here, in an attempt to
      elucidate the inhibition mechanism, we performed molecular dynamics (MD)
      simulations to demonstrate the conformational change of Abeta40 induced by ER
      molecules in atomistic detail. During the simulation, the ER bound to the
      surfaces of both N-terminus and C-terminus regions of Abeta40. Our result shows
      that ER interacts with the aromatic side chains at the N-terminus region
      resulting in destabilization of the inter-chain stacking of Abeta40. Moreover,
      the stablility of the helical structures at the residues from 13 to 16 suggests
      that ER disturbs conformational transition of Abeta40. At the C-terminus region,
      the bound ER blocks water molecules and stabilizes the alpha-helical structure.
      Regardless of the number of ER molecules used, the interruption of the formation
      of the salt-bridge between aspartic acid 23 and lysine 28 occurred. To further
      validate our analysis, binding free energies of ER at each binding site were
      evaluated. The finding of stronger binding energy at the N-terminus region
      supports an inhibition mechanism induced by stacking interaction between ER and
      phenylalanine. These findings could aid present and future treatment studies for
      AD by clarifying the inhibition mechanism of ER on the conformational transition
      of Abeta40 at the molecular level.

PMID- 27021212
TI  - Spin crossover properties of enantiomers, co-enantiomers, racemates, and co
      racemates.
AB  - Through multi-component self-assembly of chiral phenylethylamine, 1-alkyl-2
      imidazolecarboxaldehyde and iron(ii) ions, two couples of enantiomeric iron(ii)
      complexes , , and with the formula of fac-Lambda or Delta-[Fe(L)3](2+)(L = R or S
      1-phenyl-N-(1-alkyl-1H-imidazol-2-ylmethylene)ethanamine) have been designed and
      synthesized as building blocks. Further binary cocrystallization of the
      prefabricated enantiomers enabled us to construct spin crossover co-enantiomers
      and , racemates and , and co-racemate . Compared with in a high spin state and
      with spin crossover at 291 K, the co-enantiomers exhibited gradual spin crossover
      at a higher temperature of 301 K, and the racemic alloys showed hysteresis loops
      induced by desolvation above room temperature. It was demonstrated that molecular
      chirality could be used effectively for stereochemical engineering of spin
      crossover materials. In addition, crystal packing, intramolecular pi-pi stacking,
      intermolecular C-Hpi interactions and solvent effects were elucidated to be
      responsible for the distinct spin crossover properties. This collective
      structural and magnetic study not only enriched the spin crossover library, but
      also provided a full comparison of optically pure, homochiral, and racemic
      materials with similar molecular structures.

PMID- 27021214
TI  - Sound production by a recoiling system in the pempheridae and terapontidae.
AB  - Sound-producing mechanisms in fishes are extraordinarily diversified. We report
      here original mechanisms of three species from two families: the pempherid
      Pempheris oualensis, and the terapontids Terapon jarbua and Pelates
      quadrilineatus. All sonic mechanisms are built on the same structures. The
      rostral part of the swimbladder is connected to a pair of large sonic muscles
      from the head whereas the posterior part is fused with bony widenings of
      vertebral bodies. Two bladder regions are separated by a stretchable fenestra
      that allows forward extension of the anterior bladder during muscle contraction.
      A recoiling apparatus runs between the inner face of the anterior swimbladder and
      a vertebral body expansion. The elastic nature of the recoiling apparatus
      supports its role in helping the swimbladder to recover its initial position
      during sonic muscle relaxation. This system should aid fast contraction (between
      100 and 250Hz) of sonic muscles. There are many differences between species in
      terms of the swimbladder and its attachments to the vertebral column, muscle
      origins, and morphology of the recoiling apparatus. The recoiling apparatus found
      in the phylogenetically-related families (Glaucosomatidae, Pempheridae,
      Terapontidae) could indicate a new character within the Percomorpharia. J.
      Morphol. 277:717-724, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27021213
TI  - Positioning of centrioles is a conserved readout of Frizzled planar cell polarity
      signalling.
AB  - Planar cell polarity (PCP) signalling is a well-conserved developmental pathway
      regulating cellular orientation during development. An evolutionarily conserved
      pathway readout is not established and, moreover, it is thought that PCP mediated
      cellular responses are tissue-specific. A key PCP function in vertebrates is to
      regulate coordinated centriole/cilia positioning, a function that has not been
      associated with PCP in Drosophila. Here we report instructive input of Frizzled
      PCP (Fz/PCP) signalling into polarized centriole positioning in Drosophila wings.
      We show that centrioles are polarized in pupal wing cells as a readout of PCP
      signalling, with both gain and loss-of-function Fz/PCP signalling affecting
      centriole polarization. Importantly, loss or gain of centrioles does not affect
      Fz/PCP establishment, implicating centriolar positioning as a conserved PCP
      readout, likely downstream of PCP-regulated actin polymerization. Together with
      vertebrate data, these results suggest a unifying model of centriole/cilia
      positioning as a common downstream effect of PCP signalling from flies to
      mammals. 

PMID- 27021215
TI  - Technical aspects of neurostimulation: Focus on equipment, electric field
      modeling, and stimulation protocols.
AB  - Neuromodulation is a field of science, medicine, and bioengineering that
      encompasses implantable and non-implantable technologies for the purpose of
      improving quality of life and functioning of humans. Brain neuromodulation
      involves different neurostimulation techniques: transcranial magnetic stimulation
      (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation
      (VNS), and deep brain stimulation (DBS), which are being used both to study their
      effects on cognitive brain functions and to treat neuropsychiatric disorders. The
      mechanisms of action of neurostimulation remain incompletely understood. Insight
      into the technical basis of neurostimulation might be a first step towards a more
      profound understanding of these mechanisms, which might lead to improved clinical
      outcome and therapeutic potential. This review provides an overview of the
      technical basis of neurostimulation focusing on the equipment, the present
      understanding of induced electric fields, and the stimulation protocols. The
      review is written from a technical perspective aimed at supporting the use of
      neurostimulation in clinical practice.

PMID- 27021216
TI  - Differential effects of docoosahexaenoic and arachidonic acid on fatty acid
      composition and myosin heavy chain-related genes of slow- and fast-twitch
      skeletal muscle tissues.
AB  - Myosin heavy chain (MHC) mediates the metabolic and contractile responses of
      skeletal muscles. MHC displays different isoforms, each of which has different
      characteristics. To better understand the effect of polyunsaturated fatty acids
      in skeletal muscles, rats were fed with control-, docosahexaenoic acid (DHA)-,
      and arachidonic acid (ARA)-oil, and the effects on plasma and muscular fatty acid
      profile, oxidative stress, mRNA levels of myosin heavy chain isoforms MHC1 of
      slow-twitch muscle (SO) and MHC2A, MHC2X, and MHCB isoforms of extensor digitorum
      longus (EDL) of fast-twitch muscle were evaluated. Concomitantly, mRNA levels of
      anti-oxidative enzymes, such as, catalase, glutathione peroxidase (GPx) and
      superoxide dismutase (SOD were determined. The expressions of MHC1, MHC2A, MHC2X,
      and MHC2B were lower in the SO of the DHA-fed rats. In the EDL muscles of DHA-fed
      rats, the expressions of MHC1 and MHC2A increased; however, the expressions of
      MHC2X increased and that of the MHC2 were not altered. Oxidative stress, as
      indicated by the levels of LPO, was significantly higher in the plasma of the ARA
      fed rats, when compared with that of the DHA-fed rats. The LPO levels were higher
      both in the SO and EDL muscles of ARA-fed rats. Compared with ARA oil intake, DHA
      oil showed higher mRNA levels of GPx and SOD. Catalase expression was higher only
      in the EDL but not in the SO-type muscles. Our studies finally indicate that DHA
      and ARA differentially affect the regulation of contractile and metabolic
      properties of slow- and fast-twitch skeletal muscles. 

PMID- 27021217
TI  - Difference in the action mechanism of radon inhalation and radon hot spring water
      drinking in suppression of hyperuricemia in mice.
AB  - Although radon therapy is indicated for hyperuricemia, the underlying mechanisms
      of action have not yet been elucidated in detail. Therefore, we herein examined
      the inhibitory effects of radon inhalation and hot spring water drinking on
      potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a
      concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2
      weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results
      obtained showed that serum uric acid levels were significantly increased by the
      administration of PO. Radon inhalation or hot spring water drinking significantly
      inhibited elevations in serum uric acid levels through the suppression of
      xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative
      functions in the liver and kidney. These results suggest that radon inhalation
      inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while
      hot spring water drinking may suppress PO-induced elevations in serum uric acid
      levels through the pharmacological effects of the chemical compositions dissolved
      in it. 

PMID- 27021218
TI  - An analysis of the structure of the compound biological effectiveness factor.
AB  - This report is an analysis of the structure of the compound biological
      effectiveness (CBE) factor. The value of the CBE factor previously reported was
      revalued for the central nervous system, skin and lung. To describe the
      structure, the following terms are introduced: the vascular CBE (v-CBE),
      intraluminal CBE (il-CBE), extraluminal CBE (el-CBE) and non-vascular CBE (nv
      CBE) factors and the geometric biological factor (GBF), i.e. the contributions
      that are derived from the total dose to the vasculature, each dose to vasculature
      from the intraluminal side and the extraluminal side, the dose to the non
      vascular tissue and the factor to calculate el-CBE from il-CBE, respectively. The
      el-CBE factor element was also introduced to relate il-CBE to el-CBE factors. A
      CBE factor of 0.36 for disodium mercaptoundecahydrododecaborate (BSH) for the CNS
      was independent of the (10)B level in the blood; however, that for p-Boron-L
      phenylalanine (BPA) increased with the (10)B level ratio of the normal tissue to
      the blood (N/B). The CBE factor was expressed as follows: factor = 0.32 + N/B *
      1.65. The factor of 0.32 at 0 of N/B was close to the CBE factor for BSH. GBFs
      had similar values, between BSH and BPA, 1.39 and 1.52, respectively. The
      structure of the CBE factor for BPA to the lung was also elucidated based on this
      idea. The factor is described as follows: CBE factor = 0.32 + N/B * 1.80. By this
      elucidation of the structure of the CBE factor, it is expected that basic and
      clinical research into boron neutron capture therapy will progress. 

PMID- 27021219
TI  - Multi-locus sequence data reveal a new species of coral reef goby (Teleostei:
      Gobiidae: Eviota), and evidence of Pliocene vicariance across the Coral Triangle.
AB  - Here, multi-locus sequence data are coupled with observations of live colouration
      to recognize a new species, Eviota punyit from the Coral Triangle, Indian Ocean
      and Red Sea. Relaxed molecular clock divergence time estimation indicates a
      Pliocene origin for the new species, and the current distribution of the new
      species and its sister species Eviota sebreei supports a scenario of vicariance
      across the Indo-Pacific Barrier, followed by subsequent range expansion and
      overlap in the Coral Triangle. These results are consistent with the 'centre of
      overlap' hypothesis, which states that the increased diversity in the Coral
      Triangle is due in part to the overlapping ranges of Indian Ocean and Pacific
      Ocean faunas. These findings are discussed in the context of other geminate pairs
      of coral reef fishes separated by the Indo-Pacific Barrier. 

PMID- 27021220
TI  - Anatomocosmetic implication rules of the corrugator supercilii muscle for
      youthful eye appearance.
AB  - The dynamic balance of the eyebrows is maintained by the frontal muscle which
      acts as a brow elevator, and the brow depressors include corrugator supercilii
      muscle (CSM), procerus, depressor supercilii, and orbicularis oculi muscles. The
      glabellar rhytids might appear as a result of negative emotions, such as anger,
      anxiety, fatigue, fear, or disapproval. For youthful and calmer eyes, CSM may
      restore the muscle balance more safely and effectively for the treatments of
      forehead rejuvenation. In 50 cadaver hemibrows, CSM was dissected to investigate
      the location, position, muscle patterns, and its relationships to other muscles.
      The location of the CSM was variable; five different CSM patterns were defined.
      Pattern 1: rectangular-shaped classical type was observed with the frequency of
      42.5 %. Also, three bellies were present in 25 %, and duplicate muscle in 12.5 %.
      Irregular flat (15 %) and hypoplastic types (5 %) were introduced as previously
      unidentified patterns. In muscle specimens, 30 % had complete symmetry, 45 %
      complete asymmetry, and 25 % semi-assymetry. Mean CSM thickness, length, and
      width were measured as 1.62 +/- 0.4, 29.24 +/- 6.4, and 12.62 +/- 3.3 mm,
      respectively. The distances of the medial origo of the CSM-midline and the
      lateral origo of the CSM-midline were measured as 5.54 +/- 4.89 and 14.62 +/-
      4.17 mm. The different patterns of the CSM were undefined previously. The
      findings manifest the necessity of botox treatment peculiar to each individual.
      As, insertion points have been releasing fibres to the peripheral muscles, it is
      an evidence of its complicated structure. The muscles in the glabella are
      difficult to demarcate precisely from surface anatomy due to overlapped muscles
      with intermingled borders, where they are attached as individual patterns. Hence,
      it might be disadvantageous that different patterns may lead to the risk of
      asymmetry of the face and brow ptosis in the postinjection period.

PMID- 27021221
TI  - A Controlled Design of Aligned and Random Nanofibers for 3D Bi-functionalized
      Nerve Conduits Fabricated via a Novel Electrospinning Set-up.
AB  - Scaffolds made of aligned nanofibers are favorable for nerve regeneration due to
      their superior nerve cell attachment and proliferation. However, it is
      challenging not only to produce a neat mat or a conduit form with aligned
      nanofibers but also to use these for surgical applications as a nerve guide
      conduit due to their insufficient mechanical strength. Furthermore, no studies
      have been reported on the fabrication of aligned nanofibers and randomly-oriented
      nanofibers on the same mat. In this study, we have successfully produced a mat
      with both aligned and randomly-oriented nanofibers by using a novel
      electrospinning set up. A new conduit with a highly-aligned electrospun mat is
      produced with this modified electrospinning method, and this proposed conduit
      with favorable features, such as selective permeability, hydrophilicity and nerve
      growth directional steering, were fabricated as nerve guide conduits (NGCs). The
      inner surface of the nerve conduit is covered with highly aligned electrospun
      nanofibers and is able to enhance the proliferation of neural cells. The central
      part of the tube is double-coated with randomly-oriented nanofibers over the
      aligned nanofibers, strengthening the weak mechanical strength of the aligned
      nanofibers. 

PMID- 27021222
TI  - SORLA regulates calpain-dependent degradation of synapsin.
AB  - INTRODUCTION: Sorting-related receptor with A-type repeats (SORLA) is an
      intracellular sorting receptor in neurons and a major risk factor for Alzheimer
      disease. METHODS: Here, we performed global proteome analyses in the brain of
      SORLA-deficient mice followed by biochemical and histopathologic studies to
      identify novel neuronal pathways affected by receptor dysfunction. RESULTS: We
      demonstrate that the lack of SORLA results in accumulation of phosphorylated
      synapsins in cortex and hippocampus. We propose an underlying molecular mechanism
      by demonstrating that SORLA interacts with phosphorylated synapsins through 14-3
      3 adaptor proteins to deliver synapsins to calpain-mediated proteolytic
      degradation. DISCUSSION: Our results suggest a novel function for SORLA which is
      in control of synapsin degradation, potentially impacting on synaptic vesicle
      endocytosis and/or exocytosis.

PMID- 27021223
TI  - Reliability of the modified Tufts Lumbar Degenerative Disc Classification between
      neurosurgeons and neuroradiologists.
AB  - Cross-specialty inter-rater reliability has not been explicitly reported for
      imaging characteristics that are thought to be important in lumbar intervertebral
      disc degeneration. Sufficient cross-specialty reliability is an essential
      consideration if radiographic stratification of symptomatic patients to specific
      treatment modalities is to ever be realized. Therefore the purpose of this study
      was to directly compare the assessment of such characteristics between
      neurosurgeons and neuroradiologists. Sixty consecutive patients with a diagnosis
      of lumbago and appropriate imaging were selected for inclusion. Lumbar MRI were
      evaluated using the Tufts Degenerative Disc Classification by two neurosurgeons
      and two neuroradiologists. Inter-rater reliability was assessed using Cohen's
      kappa values both within and between specialties. A sensitivity analysis was
      performed for a modified grading system, which excluded high intensity zones
      (HIZ), due to poor cross-specialty inter-rater reliability of HIZ between
      specialties. The reliability of HIZ between neurosurgeons and neuroradiologists
      was fair in two of the four cross-specialty comparisons in this study
      (neurosurgeon 1 versus both radiologists kappa=0.364 and kappa=0.290). Removing
      HIZ from the classification improved inter-rater reliability for all comparisons
      within and between specialties (0.465?kappa?0.576). In addition, intra-rater
      reliability remained in the moderate to substantial range (0.523?kappa?0.649).
      Given our findings and corroboration with previous studies, identification of HIZ
      seems to have a markedly variable reliability. Thus we recommend modification of
      the original Tufts Degenerative Disc Classification by removing HIZ in order to
      make the overall grade provided by this classification more reproducible when
      scored by practitioners of different training backgrounds. 

PMID- 27021224
TI  - Diagnostic accuracy of somatosensory evoked potential monitoring during scoliosis
      fusion.
AB  - The goal of this review was to ascertain the diagnostic accuracy of
      intraoperative somatosensory evoked potential (SSEP) changes to predict
      perioperative neurological outcome in patients undergoing spinal deformity
      surgery to correct adolescent idiopathic scoliosis (AIS). The authors searched
      PubMed/MEDLINE and World Science databases to retrieve reports and/or experiments
      from January 1950 through January 2014 for studies on SSEP use during AIS
      surgery. All motor and sensory deficits were noted in the neurological
      examination administered after the procedure which was used to determine the
      effectiveness of SSEP as an intraoperative monitoring technique. Fifteen studies
      identified a total of 4763 procedures on idiopathic patients. The observed
      incidence of neurological deficits was 1.11% (53/4763) of the sample population.
      Of the patients with new postoperative neurological deficits 75.5% (40/53) showed
      significant SSEP changes, and 24.5% (13/53) did not show significant change.
      Pooled analysis using the bivariate model showed SSEP change with pooled
      sensitivity (average 84%, 95% confidence interval 59-95%) and specificity
      (average 98%, 95% confidence interval 97-99%). The diagnostic odds ratio of a
      patient who had a new neurological deficit with SSEP changes was a diagnostic
      odds ratio of 340 (95% confidence interval 125-926). Overall, detection of SSEP
      changes had excellent discriminant ability with an area under the curve of 0.99.
      Our meta-analysis covering 4763 operations on idiopathic patients showed that it
      is a highly sensitive and specific test and that iatrogenic spinal cord injury
      resulting in new neurological deficits was 340 times more likely to have changes
      in SSEP compared to those without any new deficits. 

PMID- 27021225
TI  - Evaluation of a filament perforation model for mouse subarachnoid hemorrhage
      using 7.0 Tesla MRI.
AB  - The filament perforation model (FPM) in mice is becoming increasingly popular to
      elucidate the molecular pathogenesis of neuronal injury after subarachnoid
      hemorrhage (SAH). We evaluated brain MRI in a mouse FPM. A total of 28 male
      C57Bl/6J mice were used. Seventeen animals underwent SAH induction by FPM. In two
      animals, transient middle cerebral artery occlusion (MCAo) was induced. Nine mice
      served as controls. T1-weighted images (T1WI), T2-weighted images (T2WI), T2(*)
      weighted images (T2*WI) and apparent diffusion coefficient maps were acquired at
      day 0 and at various time points following SAH (range: day 1-6 after SAH).
      Cerebral blood flow (CBF) analysis by (14)C-iodoamphetamine ((14)C-IMP)
      autoradiography was conducted in nine animals. Hemorrhage could be best confirmed
      using T2*WI. The degree of hemorrhage varied. All animals evaluated for ?2days
      were hydrocephalic, which was best seen on T2WI. T2-hyperintensity of the corpus
      callosum and external capsule, indicating white matter (WM) injury, was present
      after SAH. Ventricle and WM injury volumes were statistically significantly
      higher at day 3 compared to day 0. Territorial ischemia was detectable in MCAo
      but not in SAH. Markedly hypointense cortical veins were visible in the
      hyperacute and delayed phase after SAH on T2*WI. The (14)C-IMP analysis indicated
      decreased CBF after SAH. MRI is feasible and useful in evaluating
      pathophysiological changes over time. T2*WI seems best for SAH detection and
      grading. The chronological change of hydrocephalus and WM injury could be
      analyzed. T2*WI illustrated specific signal changes of cortical veins, possibly
      caused by increased oxygen extraction fraction due to decreased CBF. 

PMID- 27021226
TI  - Gastrocnemius and soleus spasticity and muscle length in Friedreich's ataxia.
AB  - Lower limb spasticity compromises the independence of people with Friedreich's
      ataxia (FRDA). This study sought to examine lower limb spasticity in FRDA in
      order to offer new insight as to the best approach and timing of spasticity
      management. Gastrocnemius and soleus spasticity and muscle length were measured
      by the Modified Tardieu Scale (MTS) in 31 participants with typical and late
      onset FRDA. Relationships between the MTS and the Friedreich Ataxia Rating Scale
      (FARS), Functional Independence Measure (FIM), and disease duration were
      analysed. Differences between ambulant (n=18) and non-ambulant (n=13)
      participants were also examined. All participants had spasticity in at least one
      muscle, and 38.9% of ambulant and 69.2% of non-ambulant participants had
      contracture in one or both of their gastrocnemius muscles. Significant negative
      correlations were found between both gastrocnemius and soleus angle of catch and
      the FARS score. The FIM score also demonstrated significant correlations with
      gastrocnemius muscle length and angle of catch. Gastrocnemius and soleus
      spasticity and contracture is apparent in people with FRDA. Spasticity is evident
      early in the disease and in ambulant participants. Management of spasticity and
      reduced muscle length should be considered in people with FRDA at disease onset
      to optimise function. 

PMID- 27021227
TI  - Impact of obesity on lumbar spinal surgery outcomes.
AB  - Controversy exists regarding the effect of obesity on surgical outcomes and
      complications following lumbar spinal surgery. A systematic electronic literature
      review of all relevant studies through to June 2015 was performed using the
      PubMed, Embase, and Cochrane library databases. Pooled risk ratios (RR) or
      standardised mean differences (SMD) with 95% confidence intervals (CI) were
      calculated using random or fixed effects models. The Newcastle-Ottawa Scale was
      used to evaluate the methodological quality, and Stata 11.0 was used to analyse
      data (StataCorp, College Station, TX, USA). Significant differences between obese
      and non-obese patients were found for operation time (SMD, -0.273; 95%CI, -0.424
      to -0.121), blood loss (SMD, -0.265; 95%CI, -0.424 to -0.107), surgical site
      infections (RR, 0.610; 95%CI, 0.446 to 0.834), and nerve injury (RR, 0.188;
      95%CI, 0.042 to 0.841). Deep vein thrombosis, dural tear, revision surgery, and
      mortality were not significantly differences between the two groups (P<0.05).
      Obesity appears to be associated with longer operative times, greater blood loss,
      and higher risk of surgical site infections and nerve injuries. However, the
      results of this meta-analysis should be interpreted with caution due to
      heterogeneity amongst the included studies. 

PMID- 27021228
TI  - Molecular cytogenetic identification of a wheat-rye 1R addition line with
      multiple spikelets and resistance to powdery mildew.
AB  - Alien addition lines are important for transferring useful genes from alien
      species into common wheat. Rye is an important and valuable gene resource for
      improving wheat disease resistance, yield, and environment adaptation. A new
      wheat-rye addition line, N9436B, was developed from the progeny of the cross of
      common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) cultivar Shaanmai 611
      and rye (Secale cereal L., 2n = 2x = 14, RR) accession Austrian rye. We
      characterized this new line by cytology, genomic in situ hybridization (GISH),
      fluorescence in situ hybridization (FISH), molecular markers, and disease
      resistance screening. N9436B was stable in morphology and cytology, with a
      chromosome composition of 2n = 42 + 2t = 22II. GISH investigations showed that
      this line contained two rye chromosomes. GISH, FISH, and molecular maker
      identification suggested that the introduced R chromosome and the missing wheat
      chromosome arms were 1R chromosome and 2DL chromosome arm, respectively. N9436B
      exhibited 30-37 spikelets per spike and a high level of resistance to powdery
      mildew (Blumeria graminis f. sp. tritici, Bgt) isolate E09 at the seedling stage.
      N9436B was cytologically stable, had the trait of multiple spikelets, and was
      resistant to powdery mildew; this line should thus be useful in wheat
      improvement. 

PMID- 27021229
TI  - Effects of Cisplatin Electrochemotherapy on Human Neuroblastoma Cells.
AB  - Electrochemotherapy is the usage of electroporation to introduce chemotherapeutic
      drugs through membrane pores into target cells for cancer treatment. The
      effectiveness of chemotherapeutic drugs would be increased dramatically when they
      are used in electrochemotherapy than standard chemotherapy. In the present study,
      we investigated the effects of cisplatin treatment with electroporation on human
      SH-SY5Y neuroblastoma cells. SH-SY5Y cells were treated with different
      concentrations (0.15-24 ug/mL) of cisplatin and then exposed to 1500 volts per
      centimeter (V/cm), 100 microseconds (us) pulse duration, and 1 Hertz (Hz)
      electric pulses. Cisplatin alone showed a dose-dependent effect on cell
      viability. On the other hand, cisplatin + electroporation treatment was more
      effective than cisplatin treatment alone. Lower doses of cisplatin treatment with
      electroporation was as effective as higher doses of cisplatin treatment without
      electroporation. These results indicated that cisplatin cytotoxicity was
      potentiated after exposure of cells to high intensity electric pulses and low
      doses of cisplatin can be used with electroporation in the treatment of
      neuroblastoma.

PMID- 27021230
TI  - Applying Transcranial Magnetic Stimulation (TMS) Over the Dorsal Visual Pathway
      Induces Schizophrenia-like Disruption of Perceptual Closure.
AB  - Perceptual closure ability is postulated to depend upon rapid transmission of
      magnocellular information to prefrontal cortex via the dorsal stream. In
      contrast, illusory contour processing requires only local interactions within
      primary and ventral stream visual regions, such as lateral occipital complex.
      Schizophrenia is associated with deficits in perceptual closure versus illusory
      contours processing that is hypothesized to reflect impaired magnocellular/dorsal
      stream. Perceptual closure and illusory contours performance was evaluated in
      separate groups of 12 healthy volunteers during no TMS, and during repetitive 10
      Hz rTMS stimulation over dorsal stream or vertex (TMS-vertex). Perceptual closure
      and illusory contours were performed in 11 schizophrenia patients, no TMS was
      applied in these patients. TMS effects were evaluated with repeated measures
      ANOVA across treatments. rTMS significantly increased perceptual closure
      identification thresholds, with significant difference between TMS-dorsal stream
      and no TMS. TMS-dorsal stream also significantly reduced perceptual closure but
      not illusory contours accuracy. Schizophrenia patients showed increased
      perceptual closure identification thresholds relative to controls in the no TMS
      condition, but similar to controls in the TMS-dorsal stream condition.
      Conclusions of this study are that magnocellular/dorsal stream input is critical
      for perceptual closure but not illusory contours performance, supporting both
      trickledown theories of normal perceptual closure function, and
      magnocellular/dorsal stream theories of visual dysfunction in schizophrenia.

PMID- 27021231
TI  - The role of social buffering on chronic disruptions in quality of care: evidence
      from caregiver-based interventions in foster children.
AB  - There is growing evidence that social support can buffer the physiological stress
      response, specifically cortisol reactivity. We use a developmental framework to
      review the importance of social buffering in early childhood, a period of
      heightened plasticity for programming of the hypothalamic-pituitary-adrenal (HPA)
      axis. The social environment, in which parents play the largest role in early
      life, is a critical agent in the developmental trajectory of the HPA axis. A
      prevailing model of social buffering primarily focuses on the role of social
      support in the context of acute stressors and cortisol response. This review
      expands this model to provide evidence of the mechanism of social buffering, or
      lack thereof, across periods of chronic stress by applying the social buffer
      model to children involved in the child welfare system. We also highlight current
      interventions that capitalize on the mechanism of social buffering to modify HPA
      axis functioning across childhood. Last, we synthesize our findings using the
      social buffering framework to inform future targeted interventions.

PMID- 27021232
TI  - Effect of angiotensin II type 1 receptor blocker on 12-lipoxygenase activity and
      slit diaphragm protein expression in type 2 diabetic rat glomeruli.
AB  - BACKGROUND: The 12-lipoxygenase (12-LO) and angiotensin II (Ang II) interaction
      plays an important role in diabetic nephropathy (DN). Proteinuria in DN is
      associated with decreased slit diaphragm proteins including nephrin and P
      cadherin. Therefore, we investigated whether Ang II type 1 receptor (AT1) blocker
      (ARB) regulates 12-LO activity and slit diaphragm protein expression in diabetic
      rat glomeruli. METHOD: Glomeruli were isolated with the sieving method, and
      classified into small glomeruli (SG; 75-MUm sieve) and large glomeruli (LG; 125
      MUm sieve). RESULTS: 12(S)-HETE, a lipid product of 12-LO, was increased by Ang
      II in the glomeruli. Infusion of 12(S)-HETE and Ang II significantly decreased
      nephrin expression in LG, but increased it in SG compared to control. Glomerular
      P-cadherin expression was reduced after Ang II and 12(S)-HETE treatment without
      differences between LG and SG. ARB did not influence glycemic levels but
      completely abolished the increases in 12(S)-HETE, AT1 expression, and proteinuria
      in diabetic rats. Nephrin expression was significantly reduced in LG but
      increased in SG in diabetic rats compared to control. P-cadherin expression
      decreased in both diabetic LG and SG. The abnormalities of nephrin and P-cadherin
      were partially but significantly reversed by ARB. CONCLUSION: ARB potentially
      ameliorates DN via the up-regulation of glomerular nephrin and P-cadherin
      expression through the inhibition of 12-LO activation in the glomeruli of rats
      with DN.

PMID- 27021233
TI  - Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem
      cells by inducing hypoxia-inducible factor-1alpha in a co-culture system.
AB  - OBJECTIVES: Tissue engineering is a promising approach for repair of tendon
      injuries. Adipose-derived mesenchymal stem cells (ADMSCs) have gained increasing
      research interest for their potential in improving healing and regeneration of
      injured tendons. The present study aimed to investigate effects of O2 tension and
      potential signalling pathways on AMDSC differentiation into tenocytes, in an
      indirect co-culture system. MATERIALS AND METHODS: Human ADMSCs were co-cultured
      under normoxia (20% O2 ) and also under hypoxia (2% O2 ). Tenocyte
      differentiation of AMDSCs and expression of hypoxia-inducible factor-1 (HIF
      1alpha) were analysed by reverse transcription-PCR, Western blotting and
      immunohistochemistry. Furthermore, HIF-1alpha inhibitor and inducer (FG-4592)
      effects on differentiation of AMDSCs were studied using qPCR, immunofluorescence
      and Western blotting. RESULTS: Indirect co-culture with tenocytes increased
      differentiation of ADMSCs into tenocytes; furthermore, hypoxia further enhanced
      tenocyte differentiation of AMDSCs, accompanied by increased expression of HIF
      1alpha. HIF-1alpha inhibitor attenuated effects of hypoxia on differentiation of
      ADMSCs; in contrast, FG-4592 increased differentiation of ADMSCs under both
      hypoxia and normoxia. CONCLUSIONS: Taken together, we found that growing ADMSCs
      under hypoxia, or activating expression of HIF-1alpha to be important in
      differentiation of ADMSCs, which provides a foundation for application of ADMSCs
      in vivo for tendon regeneration.

PMID- 27021234
TI  - Mechanisms of pentazocine-induced ventilatory depression and antinociception in
      anesthetized rats.
AB  - This study was performed to clarify mechanisms underlying pentazocine-induced
      ventilatory depression and antinociception. Spontaneous ventilation and hind leg
      withdrawal response against nociceptive thermal stimulation were simultaneously
      recorded in anesthetized rats. Pentazocine decreased minute volume resulting from
      depression of the ventilatory rate and tracheal airflow, and prolonged the
      latency of withdrawal response. Pre-treatment of beta-funaltorexamine, but not
      nor-binaltorphimine, significantly attenuated pentazocine-induced ventilatory
      depression, while either antagonist weakened its analgesic potency. Comparing
      with effects of fentanyl and U50488, the present results suggest that ventilatory
      depression induced by pentazocine is mediated by mainly MU receptors and
      analgesia by both MU and kappa receptors. 

PMID- 27021235
TI  - Parental mosaicism in another case of Dravet syndrome caused by a novel SCN1A
      deletion: a case report.
AB  - BACKGROUND: Dravet syndrome, a rare genetic disorder with early-onset epileptic
      encephalopathy, was first described by Dravet in 1978. Dravet syndrome is most
      frequently caused by various mutations of the SCN1A gene encoding the type 1
      subunit of the neuronal voltage-gated sodium channel. CASE PRESENTATION: Two
      sisters of a non-consanguineous Palestinian family from the Arab community in
      Israel attended our child development and pediatric neurology clinic due to
      recurrent seizures and developmental delay. Genomic DNA was extracted from
      peripheral blood lymphocytes of all family members and a SCN1A mutation in exon
      10 was revealed by Sanger sequencing in both affected siblings but not in the
      parents. Our data present a case of Dravet syndrome caused by a novel
      heterozygous SCN1A deletion (c.1458_1465delCTCTAAGT) in two affected siblings.
      Our findings add to the spectrum of mutations known in the SCN1A gene and confirm
      parental mosaicism as a mechanism relevant for transmission of this disease.
      CONCLUSIONS: These cases confirm parental mosaicism in the transmission of Dravet
      syndrome and add to the spectrum of known mutations of the SCN1A gene. Repeated
      reports on parental mosaicism should remind us that there is a risk of recurrence
      even if the mutation is apparently de novo.

PMID- 27021236
TI  - Microenvironmental Effect of 2'-O-(1-Pyrenylmethyl)uridine Modified Fluorescent
      Oligonucleotide Probes on Sensitive and Selective Detection of Target RNA.
AB  - 2'-O-(1-Pyrenylmethyl)uridine modified oligoribonucleotides provide highly
      sensitive pyrene fluorescent probes for detecting specific nucleotide mutation of
      RNA targets. To develop more stable and cost-effective oligonucleotide probes, we
      investigated the local microenvironmental effects of nearby nucleobases on pyrene
      fluorescence in duplexes of RNAs and 2'-O-(1-pyrenylmethyl)uridine modified
      oligonucleotides. By incorporation of deoxyribonucleotides, ribonucleotides, 2'
      MeO-nucleotides and 2'-F-nucleotides at both sides of 2'-O-(1
      pyrenylmethyl)uridine (U(p)) in oligodeoxynucleotide probes, we synthesized a
      series of pyrene modified oligonucleotide probes. Their pyrene fluorescence
      emission spectra indicated that only two proximal nucleotides have a substantial
      effect on the pyrene fluorescence properties of these oligonucleotide probes
      hybridized with target RNA with an order of fluorescence sensitivity of 2'-F
      nucleotides > 2'-MeO-nucleotides > ribonucleotides ? deoxyribonucleotides. While
      based on circular dichroism spectra, overall helix conformations (either A- or B
      form) of the duplexes have marginal effects on the sensitivity of the probes.
      Instead, the local substitution reflected the propensity of the nucleotide sugar
      ring to adopt North type conformation and, accordingly, shifted their helix
      geometry toward a more A-type like conformation in local microenvironments. Thus,
      higher enhancement of pyrene fluorescence emission favored local A-type helix
      structures and more polar and hydrophobic environments (F > MeO > OH at 2'
      substitution) of duplex minor grooves of probes with the target RNA. Further
      dynamic simulation revealed that local microenvironmental effect of 2'-F
      nucleotides or ribonucleotides was enough for pyrene moiety to move out of
      nucleobases to the minor groove of duplexes; in addition, 2'-F-nucleotide had
      less effect on pi-stack of pyrene-modified uridine with upstream and downstream
      nucleobases. The present oligonucleotide probes successfully distinguished target
      RNA from single-mutated RNA analyte during an in vitro assay of RNA synthesis.

PMID- 27021238
TI  - An exploration of the extent and nature of reconceptualisation of pain following
      pain neurophysiology education: A qualitative study of experiences of people with
      chronic musculoskeletal pain.
AB  - OBJECTIVE: Pain neurophysiology education (PNE), a method of pain education,
      purports to work by helping patients reconceptualise their pain, shifting from a
      tissue injury model towards a biopsychosocial understanding related to neural
      sensitivity. Better understanding of pain reconceptualisation following PNE is
      needed to improve the delivery of this educational approach to enhance its
      effectiveness. This study aimed to investigate the extent and nature of
      reconceptualisation following PNE. METHODS: In a qualitative design, based on
      Interpretive Phenomenological Analysis, thematic analysis was carried out on
      individual interviews with 7 adults before and three weeks after receiving PNE at
      a pain clinic. RESULTS: Three themes emerged describing variable degrees of
      reconceptualisation; prior beliefs as facilitators and barriers to
      reconceptualisation; and the influence of reconceptualisation on clinical
      benefits of PNE. CONCLUSION: The results lend support to claims that
      reconceptualisation is an important mechanism in PNE and justify further
      investigation of this phenomenon. PRACTICAL IMPLICATIONS: When delivering PNE to
      patients with chronic pain helping patients to reconceptualise their pain may be
      key to enhancing the clinical benefits of the intervention. Understanding prior
      beliefs may be an important step in facilitating reconceptualisation.

PMID- 27021239
TI  - Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of
      palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and
      phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in
      Psoriasis (ESTEEM) clinical trials in patients with moderate to severe psoriasis.
AB  - BACKGROUND: Difficult-to-treat palmoplantar psoriasis has a disproportionately
      negative impact on quality of life. OBJECTIVE: We evaluated the efficacy and
      safety of apremilast in palmoplantar psoriasis. METHODS: A post hoc analysis of
      data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial
      Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical
      studies was conducted to determine the effect of apremilast 30 mg twice daily
      versus placebo at week 16 in a subset of patients with moderate to severe plaque
      psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis
      Physician Global Assessment [PPPGA] score >=1). RESULTS: Significantly more
      patients taking apremilast with moderate to severe palmoplantar psoriasis
      (baseline PPPGA score >=3) achieved PPPGA score 0 (clear) or 1 (almost clear)
      compared with placebo at week 16 (48% vs 27%; P = .021). At week 16, 46% of the
      apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of
      0 versus 25% of the placebo group (P < .001); 59% of the apremilast group had a
      PPPGA score of 0 or 1 with 1-point or more improvement versus 39% receiving
      placebo (P < .001). LIMITATIONS: This post hoc analysis was limited to 16 weeks
      and did not assess palmoplantar pustules, lesion localization, or surface area
      involvement. CONCLUSION: Apremilast may be a useful oral treatment option for
      patients with moderate to severe palmoplantar plaque psoriasis.

PMID- 27021240
TI  - Propranolol treatment of infantile hemangioma (IH) is not associated with
      developmental risk or growth impairment at age 4 years.
AB  - BACKGROUND: Long-term adverse effects of propranolol treatment for infantile
      hemangioma (IH) in young children have been suggested. OBJECTIVE: To compare
      growth and development in children treated with propranolol for IH with
      nontreated healthy controls. METHODS: Eighty two (73%) children with IH aged 43
      to 51 months treated with propranolol for 6 months or longer, and without other
      developmental risk factors, were recruited (cases) and matched with 4 twin
      counterparts and 78 children from a community-based cohort (control subjects).
      Parents completed the 48-months Ages and Stages Questionnaire (ASQ). Percentages
      of children with abnormal ASQ results were compared using chi(2) analyses. Mean
      ASQ scores and growth were compared using Mann-Whitney U tests. RESULTS: Six
      (7.3%) cases had abnormal ASQ results, compared with 10 (12.2%) controls (P =
      .292). Mean ASQ total score (25th-75th percentile) was 52.9 (50.8-57.0) for cases
      and 51.9 (49.0-56.0) for controls (P = .383). Height and weight of cases and
      controls were comparable. LIMITATIONS: A parent-completed screening instrument
      was used. The exclusion of children born at gestational age less than 36 weeks
      and/or children born small for gestational age partly limits generalizability.
      CONCLUSION: We found no increased developmental risk or growth impairment at age
      4 years in patients with IH treated with propranolol.

PMID- 27021241
TI  - All-solid-state high performance asymmetric supercapacitors based on novel MnS
      nanocrystal and activated carbon materials.
AB  - All-solid-state high-performance asymmetric supercapacitors (ASCs) are fabricated
      using gamma-MnS as positive electrode and porous eggplant derived activated
      carbon (EDAC) as negative electrode with saturated potassium hydroxide agar gel
      as the solid electrolyte. The laminar wurtzite nanostructure of gamma-MnS
      facilitates the insertion of hydroxyl ions into the interlayer space, and the
      manganese sulfide nanowire offers electronic transportation channels. The size
      uniform porous nanostructure of EDAC provides a continuous electron pathway as
      well as facilitates short ionic transportation pathways. Due to these special
      nanostructures of both the MnS and the EDAC, they exhibited a specific
      capacitance of 573.9 and 396 F g(-1) at 0.5 A g(-1), respectively. The optimized
      MnS//EDAC asymmetric supercapacitor shows a superior performance with specific
      capacitance of 110.4 F g(-1) and 89.87% capacitance retention after 5000 cycles,
      a high energy density of 37.6 Wh kg(-1) at a power density of 181.2 W kg(-1) and
      remains 24.9 Wh kg(-1) even at 5976 W kg(-1). Impressively, such two assembled
      all-solid-state cells in series can light up a red LED indicator for 15 minutes
      after fully charged. These impressive results make these pollution-free materials
      promising for practical applications in solid aqueous electrolyte-based ASCs.

PMID- 27021242
TI  - Eating Disorders in Adolescents With Chronic Pain.
AB  - INTRODUCTION: Given that youth with chronic pain frequently experience
      disruptions in eating patterns that may place them at risk for disordered eating,
      the purpose of this study was to examine the clinical characteristics and illness
      course of adolescents with chronic pain and comorbid eating disorders. METHODS:
      Using a retrospective chart review, 34 adolescents with chronic pain and
      concurrent eating disorders were identified. These adolescents were compared with
      34 age-, gender-, and eating disorder symptom-matched adolescents who had an
      eating disorder without chronic pain. RESULTS: The majority of adolescents with
      chronic pain and an eating disorder had a primary medical diagnosis of abdominal
      pain (n = 14), followed by autonomic dysfunction (n = 10) and headache (n = 6).
      Although in 41.2% of teens with chronic pain, eating disorder symptoms developed
      after the onset of their pain, 35.3% reported having eating disorder symptoms
      before they experienced chronic pain. Body mass index did not differ between the
      groups, but the duration of eating disorder symptoms was significantly longer for
      the chronic pain group (p < .001). DISCUSSION: Despite comparable severity,
      eating disorders are undetected for longer periods in patients with chronic pain,
      which may contribute to a poorer prognosis. Implications for eating disorder
      conceptualization, detection, and treatment are discussed.

PMID- 27021243
TI  - Determination of Active Phagocytosis of Unopsonized Porphyromonas gingivalis by
      Macrophages and Neutrophils Using the pH-Sensitive Fluorescent Dye pHrodo.
AB  - Phagocytosis of pathogens is an important component of the innate immune system
      that is responsible for the removal and degradation of bacteria as well as their
      presentation via the major histocompatibility complexes to the adaptive immune
      system. The periodontal pathogen Porphyromonas gingivalis exhibits strain
      heterogeneity, which may affect a phagocyte's ability to recognize and
      phagocytose the bacterium. In addition, P. gingivalis is reported to avoid
      phagocytosis by antibody and complement degradation and by invading phagocytic
      cells. Previous studies examining phagocytosis have been confounded by both the
      techniques employed and the potential of the bacteria to invade the cells. In
      this study, we used a novel, pH-sensitive dye, pHrodo, to label live P.
      gingivalis strains and examine unopsonized phagocytosis by murine macrophages and
      neutrophils and human monocytic cells. All host cells examined were able to
      recognize and phagocytose unopsonized P. gingivalis strains. Macrophages had a
      preference to phagocytose P. gingivalis strain ATCC 33277 over other strains and
      clinical isolates in the study, whereas neutrophils favored P. gingivalis W50,
      ATCC 33277, and one clinical isolate over the other strains. This study revealed
      that all P. gingivalis strains were capable of being phagocytosed without prior
      opsonization with antibody or complement.

PMID- 27021244
TI  - Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the
      Pathogenic Life Cycle of the Spirochete.
AB  - Borrelia burgdorferi possesses a sophisticated chemotaxis signaling system;
      however, the roles of the majority of the chemotaxis proteins in the infectious
      life cycle have not yet been demonstrated. Specifically, the role of CheD during
      host colonization has not been demonstrated in any bacterium. Here, we
      systematically characterized the B. burgdorferi CheD homolog using genetics and
      biochemical and mouse-tick-mouse infection cycle studies. Bacillus subtilis CheD
      plays an important role in chemotaxis by deamidation of methyl-accepting
      chemotaxis protein receptors (MCPs) and by increasing the receptor kinase
      activity or enhancing CheC phosphatase activity, thereby regulating the levels of
      the CheY response regulator. Our biochemical analysis indicates that B.
      burgdorferi CheD significantly enhances CheX phosphatase activity by specifically
      interacting with the phosphatase. Moreover, CheD specifically binds two of the
      six MCPs, indicating that CheD may also modulate the receptor proteins. Although
      the motility of the cheD mutant cells was indistinguishable from that of the wild
      type cells, the mutant did exhibit reduced chemotaxis. Importantly, the mutant
      showed significantly reduced infectivity in C3H/HeN mice via needle inoculation.
      Mouse-tick-mouse infection assays indicated that CheD is dispensable for
      acquisition or transmission of spirochetes; however, the viability of cheD
      mutants in ticks is marginally reduced compared to that of the wild-type or
      complemented cheD spirochetes. These data suggest that CheD plays an important
      role in the chemotaxis and pathogenesis of B. burgdorferi We propose potential
      connections between CheD, CheX, and MCPs and discuss how these interactions play
      critical roles during the infectious life cycle of the spirochete.

PMID- 27021245
TI  - Meningococcal Factor H Binding Protein Vaccine Antigens with Increased Thermal
      Stability and Decreased Binding of Human Factor H.
AB  - Neisseria meningitidis causes cases of bacterial meningitis and sepsis. Factor H
      binding protein (FHbp) is a component of two licensed meningococcal serogroup B
      vaccines. FHbp recruits the complement regulator factor H (FH) to the bacterial
      surface, which inhibits the complement alternative pathway and promotes immune
      evasion. Binding of human FH impairs the protective antibody responses to FHbp,
      and mutation of FHbp to decrease binding of FH can increase the protective
      responses. In a previous study, we identified two amino acid substitutions in
      FHbp variant group 2 that increased its thermal stability by 21 degrees C and
      stabilized epitopes recognized by protective monoclonal antibodies (MAbs). Our
      hypothesis was that combining substitutions to increase stability and decrease FH
      binding would increase protective antibody responses in the presence of human FH.
      In the present study, we generated four new FHbp single mutants that decreased FH
      binding and retained binding of anti-FHbp MAbs and immunogenicity in wild-type
      mice. From these mutants, we selected two, K219N and G220S, to combine with the
      stabilized double-mutant FHbp antigen. The two triple mutants decreased FH
      binding >200-fold, increased the thermal stability of the N-terminal domain by 21
      degrees C, and bound better to an anti-FHbp MAb than the wild-type FHbp. In human
      FH-transgenic mice, the FHbp triple mutants elicited 8- to 15-fold-higher
      protective antibody responses than the wild-type FHbp antigen. Collectively, the
      data suggest that mutations to eliminate binding of human FH and to promote
      conformational stability act synergistically to optimize FHbp immunogenicity.

PMID- 27021247
TI  - Applicability of avidin protein coated mesoporous silica nanoparticles as drug
      carriers in the lung.
AB  - Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties
      and are thus considered as promising candidates for next generation nano
      medicines. In particular, inhalation into the lungs represents a direct, non
      invasive delivery route for treating lung disease. To assess MSN biocompatibility
      in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as
      well as aminated (uncoated) MSNs, after direct application into the lungs of
      mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and
      inflammatory responses to MSNs within one week after instillation. We show that
      amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial
      cells, but induced a prolonged inflammatory response in the lung and macrophage
      cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and
      type 2 cells in the lung in the absence of sustained inflammatory responses or
      cell death, and showed preferential epithelial cell uptake in in vitro co
      cultures. Further, MSN-AVI particles demonstrated uniform particle distribution
      in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin
      functionalized MSNs (MSN-AVI) have the potential to serve as versatile
      biocompatible drug carriers for lung-specific drug delivery. 

PMID- 27021246
TI  - Coxiella burnetii Infects Primary Bovine Macrophages and Limits Their Host Cell
      Response.
AB  - Although domestic ruminants have long been recognized as the main source of human
      Q fever, little is known about the lifestyle that the obligate intracellular Gram
      negative bacterium Coxiella burnetii adopts in its animal host. Because
      macrophages are considered natural target cells of the pathogen, we established
      primary bovine monocyte-derived macrophages (MDM) as an in vitro infection model
      to study reservoir host-pathogen interactions at the cellular level. In addition,
      bovine alveolar macrophages were included to take cell type peculiarities at a
      host entry site into account. Cell cultures were inoculated with the virulent
      strain Nine Mile I (NMI; phase I) or the avirulent strain Nine Mile II (NMII;
      phase II). Macrophages from both sources internalized NMI and NMII. MDM were
      particularly permissive for NMI internalization, but NMI and NMII replicated with
      similar kinetics in these cells. MDM responded to inoculation with a general
      upregulation of Th1-related cytokines such as interleukin-1beta (IL-1beta), IL
      12, and tumor necrosis factor alpha (TNF-alpha) early on (3 h postinfection).
      However, inflammatory responses rapidly declined when C. burnetii replication
      started. C. burnetii infection inhibited translation and release of IL-1beta and
      vastly failed to stimulate increased expression of activation markers, such as
      CD40, CD80, CD86, and major histocompatibility complex (MHC) molecules. Such
      capability of limiting proinflammatory responses may help Coxiella to protect
      itself from clearance by the host immune system. The findings provide the first
      detailed insight into C. burnetii-macrophage interactions in ruminants and may
      serve as a basis for assessing the virulence and the host adaptation of C.
      burnetii strains.

PMID- 27021248
TI  - Chromosome evolution in malaria mosquitoes inferred from physically mapped genome
      assemblies.
AB  - Polymorphic inversions in mosquitoes are distributed nonrandomly among
      chromosomes and are associated with ecological, behavioral, and physiological
      adaptations related to pathogen transmission. Despite their significance, the
      patterns and mechanism of genome rearrangements are not well understood. Recent
      sequencing and physical mapping of the genomes for 16 Anopheles mosquito species
      provided an opportunity to study chromosome evolution at the highest resolution.
      New studies revealed that fixed rearrangement accumulated [Formula: see text]3
      times faster on the X chromosome than on autosomes. The highest densities of
      transposable elements (TEs) and satellites of different sizes have also been
      found on the X chromosome, suggesting a mechanism for the inversion generation.
      The high rate of X chromosome rearrangements is in sharp contrast with the
      paucity of polymorphic inversions on the X in the majority of anopheline species.
      This paper highlights the advances in understanding chromosome evolution in
      malaria vectors and discusses possible future directions in studying mechanisms
      and biological roles of genome rearrangements.

PMID- 27021249
TI  - History of chromosome rearrangements reflects the spatial organization of yeast
      chromosomes.
AB  - Three-dimensional (3D) organization of genomes affects critical cellular
      processes such as transcription, replication, and deoxyribo nucleic acid (DNA)
      repair. While previous studies have investigated the natural role, the 3D
      organization plays in limiting a possible set of genomic rearrangements following
      DNA repair, the influence of specific organizational principles on this process,
      particularly over longer evolutionary time scales, remains relatively unexplored.
      In budding yeast S.cerevisiae, chromosomes are organized into a Rabl-like
      configuration, with clustered centromeres and telomeres tethered to the nuclear
      periphery. Hi-C data for S.cerevisiae show that a consequence of this Rabl-like
      organization is that regions equally distant from centromeres are more frequently
      in contact with each other, between arms of both the same and different
      chromosomes. Here, we detect rearrangement events in Saccharomyces species using
      an automatic approach, and observe increased rearrangement frequency between
      regions with higher contact frequencies. Together, our results underscore how
      specific principles of 3D chromosomal organization can influence evolutionary
      events.

PMID- 27021250
TI  - Clinical features, outcomes, and survival factor in patients with vertebral
      osteomyelitis infected by methicillin-resistant staphylococci.
AB  - PURPOSE: To elucidate clinico-radiological features, therapeutic outcomes, and
      survival factors of vertebral osteomyelitis patients infected by methicillin
      resistant staphylococci (MRS). METHODS: Vertebral osteomyelitis patients admitted
      to the orthopaedic department between 2007 and 2011 (n = 248) were selected for
      this multicenter study. We compared patients' backgrounds, therapeutic course,
      and in-hospital mortality between MRS and methicillin-susceptible staphylococci
      (MSS). We also examined survival factors of vertebral osteomyelitis due to MRS.
      RESULTS: Sixteen patients of MRS vertebral osteomyelitis and 55 patients of MSS
      were included in this study. In MRS vertebral osteomyelitis, the rates of
      comorbid diabetes mellitus, involvement of >2 vertebral bodies, in-hospital
      mortality, and operation of surgical debridement were higher compared to those in
      MSS vertebral osteomyelitis. Univariate analysis showed that operation of
      surgical debridement was a factor related to survival in MRS patients.
      CONCLUSIONS: Higher rate of comorbid diabetes mellitus, involvement of >2
      vertebral bodies, in-hospital mortality, and performing surgical debridement are
      peculiar features of MRS vertebral osteomyelitis compared to MSS vertebral
      osteomyelitis. If patients with MRS vertebral osteomyelitis respond poorly to
      antibiotic therapy, it might be better to consider surgical debridement not to
      lose an opportunity of operation due to exacerbation of systemic conditions.

PMID- 27021251
TI  - Lumbar spondylosis, lumbar spinal stenosis, knee pain, back muscle strength are
      associated with the locomotive syndrome: Rural population study in Japan.
AB  - OBJECTIVES: To comprehensively investigate the clinical and physical factors
      associating with locomotive syndrome (Loc-S); the locomotorium-disability for
      daily life. METHODS: 647 volunteers participated (247 males, 400 females, Age:
      58.4 +/- 11.0, BMI: 22.5 +/- 3.3). Three self-assessment questionnaires were
      administered: 1) "25-question Geriatric Locomotive Function Scale" (GFLS-25) for
      evaluating Loc-S (GLFS-25 >= 16 defined as Loc-S); 2) "diagnostic support tool
      for LSS" (LSS-DST) for evaluating the prevalence of lumbar spinal stenosis (LSS);
      3) Knee injury and Osteoarthritis Outcome Score (KOOS). Plain radiographs of the
      bilateral knees and lumbar spine were evaluated, and the severity of lumbar
      spondylosis (LS) and knee osteoarthritis (KOA) defined by Kellgren-Lawrence
      grade. Bone status was evaluated by using the osteo-sono assessment index (OSI)
      at the calcaneus. Isometric muscle strength of trunk and leg (Nm/kg, both
      extension and flexion) were evaluated. Linear regression analysis was performed
      to elucidate the factors concerned with GFLS-25 including age, sex, and BMI.
      RESULTS: Thirty-nine subjects (6.0%, 13 males, 26 females) were defined as having
      Loc-S. Single regression model showed that age, height, BMI, skeletal muscle
      mass, OSI, LSS, KOOS, the severity of LS and KOA, and trunk- and leg-muscle
      strength were correlated with the degree of GLFS-25. Stepwise multiple regression
      model showed that sex, height, LSS, KOOS, the severity of LS, and back muscle
      strength were significantly correlated with that of GLFS-25. CONCLUSION: In this
      cross-sectional study, pain status associated with LSS and knee joint, structural
      severity for LS, and back muscle strength primarily affected the degree of GFLS
      25. For managing Loc-S, we must pay more intensive attention to these factors.

PMID- 27021252
TI  - Efficient removal of cyclobutane pyrimidine dimers in barley: differential
      contribution of light-dependent and dark DNA repair pathways.
AB  - Barley stress response to ultraviolet radiation (UV) has been intensively studied
      at both the physiological and morphological level. However, the ability of barley
      genome to repair UV-induced lesions at the DNA level is far less characterized.
      In this study, we have investigated the relative contribution of light-dependent
      and dark DNA repair pathways for the efficient elimination of cyclobutane
      pyrimidine dimers (CPDs) from the genomic DNA of barley leaf seedlings. The
      transcriptional activity of barley CPD photolyase gene in respect to the light
      growth conditions and UV-C irradiation of the plants has also been analyzed. Our
      results show that CPDs induced in the primary barley leaf at frequencies
      potentially damaging DNA at the single-gene level are removed efficiently and
      exclusively by photorepair pathway, whereas dark repair is hardly detectable,
      even at higher CPD frequency. A decrease of initially induced CPDs under dark is
      observed but only after prolonged incubation, suggesting the activation of light
      independent DNA damage repair and/or tolerance mechanisms. The green barley
      seedlings possess greater capacity for CPD photorepair than the etiolated ones,
      with efficiency of CPD removal dependent on the intensity and quality of
      recovering light. The higher repair rate of CPDs measured in the green leaves
      correlates with the higher transcriptional activity of barley CPD photolyase
      gene. Visible light and UV-C radiation affect differentially the expression of
      CPD photolyase gene particularly in the etiolated leaves. We propose that the CPD
      repair potential of barley young seedlings may influence their response to UV
      stress. 

PMID- 27021253
TI  - Lymphomatoid granulomatosis coronary vasculitis and cardiomyopathy: Depiction of
      extent and severity on cardiac CT.

PMID- 27021254
TI  - Thrombus in hypoplastic aorta: An uncommon cause of acute myocardial infarction.
AB  - A coronary artery embolism is an uncommon non-atherosclerotic cause of acute
      myocardial infarction. We present a case of coronary artery embolism in a patient
      with past history of hypoplastic left heart syndrome that was initially palliated
      via a modified Blalock-Taussig shunt followed by a Fontan anastomosis and Damus
      Kaye-Stansel type anastomosis of the pulmonary valve to the ascending hypoplastic
      aorta. In this case we demonstrate usefulness of cardiac CT to delineate the
      patient's complex anatomy, identify the presence and etiology of a thromboembolic
      event, as well as assess for appropriate response to anticoagulation therapy. 

PMID- 27021255
TI  - Sequential Changes in Cortical Excitation during Orthodontic Treatment.
AB  - Cortical excitation responding to periodontal ligament (PDL) stimulation is
      observed in the rat primary somatosensory (S1), secondary somatosensory, and
      insular oral region of the cortex (S2/IOR), which are considered to process
      somatosensation, including nociception. Our previous studies have demonstrated
      that excitatory propagation induced by PDL stimulation is facilitated in S1 and
      S2/IOR 1 d after experimental tooth movement (ETM), and tetanic stimulation of
      IOR induces long-term potentiation of cortical excitatory propagation
      consistently. These findings raise the possibility that ETM induces neuroplastic
      changes, and as a result, facilitation of cortical excitation would be sustained
      for weeks. However, no information is available about the temporal profiles of
      the facilitated cortical responses. We estimated PDL stimulation-induced cortical
      excitatory propagation in S1 and S2/IOR of rats by optical imaging 1 to 7 d after
      ETM of the maxillary first molar. ETM models showed facilitated cortical
      excitatory propagation in comparison with controls and sham groups 1 d after ETM,
      but the facilitation gradually recovered to the control level 3 to 7 d after ETM.
      Sham groups that received wire fixation without orthodontic force tended to
      enhance cortical responses, although the differences between controls and sham
      groups were almost insignificant. We also examined the relationship between
      cortical responses and expression of inflammatory cytokines, interleukin (IL)
      1beta and tumor necrosis factor (TNF)-alpha, in PDL of the first molar. The peak
      amplitude of optical signals responding to PDL stimulation tended to be increased
      in parallel to the number of IL-1beta and TNF-alpha immunopositive cells,
      suggesting that, at least in part, the enhancement of cortical responses is
      induced by PDL inflammation. These findings suggest that ETM-induced facilitation
      of cortical excitatory propagation responding to PDL stimulation 1 d after ETM
      recovers to the control level within a week. The time course of the facilitated
      cortical responses is comparable to that of pain and discomfort induced by
      clinical orthodontic treatments.

PMID- 27021256
TI  - Biomarkers in the triage of chest pain: are we making progress?

PMID- 27021257
TI  - Decidual acute atherosis and "halo of hyalinization" - A Response to "The
      aetiology of narrowed uterine arterioles in obstetric and gynaecological
      syndromes" by Dr. M.J Quinn".

PMID- 27021258
TI  - Hypoxic fetoplacental vasoconstriction: Mediated by NO, Kv channels, or both?

PMID- 27021259
TI  - A systematic comparison of two new releases of exome sequencing products: the aim
      of use determines the choice of product.
AB  - We received early access to the newest releases of exome sequencing products,
      namely Agilent SureSelect v6 (Agilent, Santa Clara, CA, USA) and NimbleGen
      MedExome (Roche NimbleGen, Basel, Switzerland), and we conducted whole exome
      sequencing (WES) of several DNA samples with each of these products in order to
      assess their performance. Here, we provide a detailed evaluation of the original,
      normalized (with respect to the different target sizes), and trimmed data sets
      and compare them in terms of the amount of duplicates, the reads on target, and
      the enrichment evenness. In addition to these general statistics, we performed a
      detailed analysis of the frequently mutated and newly described genes found in
      'The Deciphering Developmental Disorders Study' published very recently
      (Fitzgerald, T.W., Gerety, S.S., Jones, W.D., van Kogelenberg, M., King, D.A.,
      McRae, J., Morley, K.I., Parthiban, V., Al-Turki, S., Ambridge, K., et al.
      (2015). Large-scale discovery of novel genetic causes of developmental disorders.
      Nature 519, 223-228.). In our comparison, the Agilent v6 exome performs better
      than the NimbleGen's MedExome both in terms of efficiency and evenness of
      coverage distribution. With its larger target size, it is also more
      comprehensive, and therefore the better choice in research projects that aim to
      identify novel disease-associated genes. In contrast, if the exomes are mainly
      used in a diagnostic setting, we see advantages for the new NimbleGen MedExome.
      We find a superior coverage here in those genes of high clinical relevance that
      likely allows for a better detection of relevant, disease-causing mutations.

PMID- 27021260
TI  - Pharmacy language assistance resources and their association with pharmacists'
      self-efficacy in communicating with Spanish-speaking patients.
AB  - BACKGROUND: Spanish-speaking patients experience significant disparities in care
      and poorer health outcomes in comparison to English-speaking patients, often due
      to language barriers. Providers should be equipped with resources to effectively
      communicate with Spanish-speaking patients to provide the best possible care.
      PURPOSE: The purpose of this study is to examine the resources available to
      support pharmacists' communication with Spanish-speaking patients. METHODS: A
      cross-sectional study design was used to examine language-assistance resources in
      community pharmacies throughout the state of Illinois. A telephone survey
      contained items to examine the accessibility, frequency of use, ease of use, and
      helpfulness of language-assistance resources; items were rated on a 5-point
      Likert-type scale (1 = Never to 5 = Always). The survey also included nine items
      to assess pharmacists' self-efficacy in communicating with Spanish-speaking
      patients. Purposeful sampling was utilized to increase the likelihood of
      obtaining information from pharmacies serving Hispanic populations. The sample
      was categorized into high and low Spanish-speaking populations based on
      pharmacists' self-reported data. Bivariate and multivariate analyses were used to
      examine relationships between language-assistance resources and pharmacist self
      efficacy. RESULTS: A total of 231 community pharmacists participated in the
      survey. The most accessible language-assistance resources were computer-based
      (92%) and telephone help lines (80%). Among various computer-based resources,
      Spanish labels (M = 2.12, SD = 1.58) and leaflets (M = 2.04, SD = 1.49) were the
      most frequently used. Computer generated Spanish leaflets and labels, and
      language-assistance telephone lines were also perceived to be easier to use and
      more helpful in comparison to paper-based resources and personnel. Respondents
      also reported that it was easy to use friends and family (M = 3.5, SD = 1.8) and
      that they were helpful (M = 3.58, SD = 1.26). Access to computer-based resources
      (beta = 0.16, P = 0.02), and to family or friends who speak Spanish (beta = 0.24,
      P < 0.01) were significantly associated with self-efficacy (P < 0.01), after
      controlling for race and education. CONCLUSIONS: Despite having access to
      computer-based resources and language-assistance telephone lines, pharmacists
      rarely used these resources to communicate with Spanish-speaking patients.
      Efforts such as workplace resource training and pharmacy school cultural
      competency curricula should be implemented to promote as well as support
      pharmacists' use of language-assistance resources to provide optimal care to
      Spanish-speaking patients.

PMID- 27021261
TI  - Photoelectrochemical oxidation of ibuprofen via Cu2O-doped TiO2 nanotube arrays.
AB  - A p-n junction based Cu2O-doped TiO2 nanotube arrays (Cu2O-TNAs) were synthesized
      and used as a working anode in a photoelectrochemical (PEC) system. The results
      revealed that the Cu2O-TNAs were dominated by the anatase phase and responded
      significantly to visible light. XPS analyses indicated that with an amount of
      24.79% Cu doping into the structure, the band gap of Cu2O-TNAs was greatly
      reduced. SEM images revealed that the supported TiO2 nanotubes had diameters of
      approximately 80nm and lengths of about 2.63MUm. Upon doping with Cu2O, the TiO2
      nanotubes maintained their structural integrity, exhibiting no significant
      morphological change, favoring PEC applications. Under illumination, the
      photocurrent from Cu2O/TNAs was 2.4 times larger than that from TNAs, implying
      that doping with Cu2O significantly improved electron mobility by reducing the
      rate of recombination of electron-hole pairs. The EIS and Bode plot revealed that
      the estimated electron lifetimes, tauel, of TNAs and Cu2O/TNAs were 6.91 and
      26.26ms, respectively. The efficiencies of degradation of Ibuprofen by
      photoelectrochemical, photocatalytic (PC), electrochemical (EC) and photolytic
      (P) methods were measured. 

PMID- 27021262
TI  - Environmental fate of non-steroidal anti-inflammatory drugs in river
      water/sediment systems.
AB  - Laboratory tests were conducted with four non-steroidal anti-inflammatory drugs
      (naproxen, ibuprofen, diclofenac and ketoprofen) under different redox conditions
      (aerobic, anoxic, anaerobic and sulfate-reducing conditions) in order to assess
      abiotic and biotic degradation in a river water/sediment system. The river water
      was sampled from Sperchios River and the sediment was collected from the banks of
      a rural stream where the discharge point of a wastewater treatment plant is
      located. To quantitatively describe degradation kinetics of the selected
      compounds, pseudo first-order kinetics were adopted. According to the results, it
      can be stated that the concentration of the substances remained constant or
      decreased only marginally (p>=0.05) in the sterile experiments and this excludes
      abiotic processes such as hydrolysis or sorption as major removal mechanisms of
      the target compounds from the water phase and assign their removal to microbial
      action. Results showed that the removal rate of the compounds decreases as
      dissolved oxygen concentration in the river water/sediment system decreases. All
      compounds were found to be biodegradable under aerobic conditions at dissipation
      half-lives between 1.6 and 20.1days, while dissipation half-lives for naproxen
      and ketoprofen increase by a factor of 2 under all tested conditions in the
      absence of oxygen.

PMID- 27021263
TI  - Modelling the removal of volatile pollutants under transient conditions in a two
      stage bioreactor using artificial neural networks.
AB  - A two-stage biological waste gas treatment system consisting of a first stage
      biotrickling filter (BTF) and second stage biofilter (BF) was tested for the
      removal of a gas-phase methanol (M), hydrogen sulphide (HS) and alpha-pinene (P)
      mixture. The bioreactors were tested with two types of shock loads, i.e., long
      term (66h) low to medium concentration loads, and short-term (12h) low to high
      concentration loads. M and HS were removed in the BTF, reaching maximum
      elimination capacities (ECmax) of 684 and 33 gm-3h-1, respectively. P was removed
      better in the second stage BF with an ECmax of 130 gm-3h-1. The performance was
      modelled using two multi-layer perceptrons (MLPs) that employed the error
      backpropagation with momentum algorithm, in order to predict the removal
      efficiencies (RE, %) of methanol (REM), hydrogen sulphide (REHS) and alpha-pinene
      (REP), respectively. It was observed that, a MLP with the topology 3-4-2 was able
      to predict REM and REHS in the BTF, while a topology of 3-3-1 was able to
      approximate REP in the BF. The results show that artificial neural network (ANN)
      based models can effectively be used to model the transient-state performance of
      bioprocesses treating gas-phase pollutants.

PMID- 27021264
TI  - Perception of speech in cartilage conduction.
AB  - OBJECTIVE: By attaching a transducer to the aural cartilage a relatively loud
      sound is audible even with a negligibly small fixation pressure applied to the
      transducer. This form of conduction is referred to as cartilage conduction (CC).
      Utilizing CC, novel audio devices can be developed, and one possible application
      is a CC hearing aid. However, there are no studies on speech perception in CC. In
      this study, CC speech recognition performance was measured and compared with that
      for air and bone conduction (AC and BC, respectively). METHODS: Nine volunteers
      with normal hearing participated in the study. The performance-intensity
      functions were measured for AC, BC and CC. These measurements were performed in
      the conditions with and without an earplug. RESULTS: Without the earplug, no
      differences in speech recognition scores were observed among AC, BC, and CC. With
      the earplug, the level at which the maximum speech recognition score was obtained
      did not increase in CC, which agreed with the result of BC but not AC. The
      maximum speech recognition CC score decreased with the earplug. The performance
      intensity functions for AC and BC shifted in parallel with the earplug. These
      shifts approximated the average threshold shifts. In contrast, for CC, the
      performance-intensity function did not shift in parallel with the earplug. As for
      the CC threshold shifts with the earplug, although the threshold at 500Hz
      decreased by 15.4dB, those at 2000 and 4000Hz increased by 13.8 and 31.1dB,
      respectively. Compared with AC and BC, CC excessively emphasized low over high
      frequency sounds when the earplug was inserted. Confusion matrices analysis
      demonstrated that 4%, 22%, and 74% of the errors occurred at low, intermediate,
      and high frequency speech sounds, respectively. Thus, this excessive low
      frequency sound emphasis probably prevented the recognition of high frequency
      speech sounds. CONCLUSION: The decrease in the maximum speech recognition score
      for CC with the earplug was derived from the biased frequency composition. It can
      be improved by frequency composition adjustment.

PMID- 27021265
TI  - Will unilateral temporomandibular joint anterior disc displacement in teenagers
      lead to asymmetry of condyle and mandible? A longitudinal study.
AB  - PURPOSE: To evaluate the change of morphological symmetry of the
      temporomandibular joints (TMJ) during natural course of unilateral juvenile
      anterior disc displacement (UJADD) by comparing the ipsilateral joint with the
      contralateral side; and to analyse its effect over mandibular asymmetry (MA).
      PATIENTS AND METHODS: This study is a self-control longitudinal study.
      Consecutive UJADD cases with no history of TMJ infection, injuries to the jaws,
      or congenital, developmental and systematic disorders that may affect the
      craniofacial growth were collected and followed for at least 6 months. Patients'
      age at both first visit and revisit was recorded. Pictures of magnetic resonance
      imaging (MRI) were selected to measure the differences between bilateral condylar
      height, disc length and condyle-disc distance, and comparison of the measurements
      before and after follow-up were made. Meanwhile, posteroanterior cephalometric
      radiographs (PA) were taken and deviation of menton from facial midline was
      measured before and after follow-up. Severity of MA was divided into 4 stages
      according to menton deviation: Non-MA (<2 mm), Minor-MA (>=2 mm, <4 mm), Medium
      MA (>=4 mm, <6 mm), and Major-MA (>=6 mm). The constituent ratio of MA was
      evaluated and correlation between TMJ morphological change and asymmetry of the
      mandible was analysed. RESULTS: Forty four patients were included, with a mean
      follow-up of 12.22 months. The average age was 16.31 years old (range, 10-20
      years) at first visit. Significant progression of disc displacement was found:
      condyle-disc distance increased, disc shortened and difference between bilateral
      condylar heights increased. Along with this, occurrence of MA increased from
      86.36% to 93.18%, and average menton deviation increased from 5.58 mm to 7.74 mm
      after follow-up. The correlation coefficient (CC) of increase of condylar height
      difference and development of MA was 0.681 (p < 0.05). Also, increase of menton
      deviation was significantly related to age of the patients (CC = -0.760, p <
      0.05). CONCLUSION: The results show that UJADD result in asymmetric growth
      bilateral TMJs, especially condylar height, which was much shorter on the
      ipsilateral side. In the same time, MA got worse during the natural course of
      UJADD. It is concluded that UJADD was one of the major causative factors of MA.

PMID- 27021266
TI  - Functional and cosmetic outcome after closure of radial forearm free flap donor
      defect with porcine collagen membrane.
AB  - INTRODUCTION: Disadvantages of the radial forearm free flap (RFFF) are related to
      the forearm donor site, which requires skin grafting for closure. Due to that
      matter, an alternative technique using porcine collagen membrane instead of skin
      grafting was considered and evaluated for its efficacy of donor defect closure.
      MATERIAL AND METHODS: Ten patients requiring reconstruction of oral &
      maxillofacial defect underwent the single-staged reconstruction with the RFFF.
      The flap was elevated and the porcine collagen membrane (Rapiderm((r))) was fixed
      at the donor site with tie-over dressing. After leaving it for at least 2 weeks,
      it was replaced with an iodine-coated furazine gauze for continuous healing.
      RESULTS: The patients did not develop any tendon exposure or infection. All
      forearms healed within 1 month. The mean graft size harvested was 27.75 +/- 3.08
      cm(2). A greater amount of granulation tissue was formed under the dressing gauze
      which resulted in a less conspicuous donor site. After 6 months the average scar
      dimension was 9.48 +/- 1.07 cm. Appearance was excellent with good wrist motility
      and skin color. CONCLUSION: The use of the porcine collagen membrane in the donor
      site of the RFFF is an alternative approach with less morbidity compared to other
      techniques. Nevertheless, further studies with a larger number of patients are
      needed to validate the present findings.

PMID- 27021267
TI  - Pathways of priority pesticides in sediments of coastal lagoons: The case study
      of Obidos Lagoon, Portugal.
AB  - This study reports the concentrations of the priority pesticides (PPs) in 14
      surface sediments and 21 layers of a sediment core from Obidos Lagoon, a shallow
      Portuguese coastal lagoon. Results show that the PPs are confined to the upper
      part of the lagoon that receives most of the inputs from surface runoff of the
      surrounding agricultural fields and from small tributaries. Past and recent
      applied PPs were registered in sediments, aluminum normalized concentrations
      varying between 0.05*10(-7) and 6.85*10(-7). The PP risk assessment based on
      sediment quality guidelines like the "Probable Effect Level" (PEL) shows no
      biological effects in either sediments or aquatic organisms of Obidos Lagoon,
      except for dieldrin, lindane, DDT, heptachlor epoxide and its parent compound
      heptachlor. 

PMID- 27021268
TI  - Distribution of (137)Cs in the Mediterranean mussel (Mytilus galloprovincialis)
      in Eastern Black Sea Coast of Turkey.
AB  - This study presents the results of (137)Cs and (40)K radionuclide concentrations
      in mussel (Mytilus galloprovincialis) samples collected during the period of
      February-November 2014 from twelve different stations within the border of the
      eastern Black Sea region of Turkey. Also, these radionuclide concentrations were
      determined in sea water and sediment samples. The activity concentrations in
      seawater, sediment and mussel tissue samples were between 1.12-1.69mBqL(-1), 3.26
      30.74 and 1.61-3.16Bqkg(-1) for (137)Cs and 231.41-399.49mBqL(-1), 215.71-450.07
      and 286.84-382.16Bqkg(-1) for (40)K, respectively. These values are also in
      accordance with the concentrations reported for similar regions. Additionally,
      radiological impact parameters such as daily intake of (137)Cs and (40)K, annual
      committed effective dose and carcinogenic risk due to the consumption of mussel
      were calculated and compared with the international data. Lifetime cancer risk
      values are lower than the limit of 10(-3). 

PMID- 27021269
TI  - Co-infection with Plasmodium berghei and Trypanosoma brucei increases severity of
      malaria and trypanosomiasis in mice.
AB  - Individuals in natural populations may be infected with multiple different
      parasites at a time. These parasites may interact with each other or act
      independently in the host, and this may result to varying outcomes on host health
      and survival. This study therefore aimed at investigating the health impact of co
      infection of mice with Plasmodium berghei and Trypanosoma brucei. Forty Swiss
      albino mice (14-17g) were divided into four groups of ten. Mice in groups A and B
      received 10(6)P. berghei and groups B and C 10(5)T. brucei, while group D were
      uninfected. The co-infected mice had higher P. berghei and T. brucei
      parasitaemia, compared with the mono-infected mice. The co-infected mice had
      significantly (p<0.05) lower survival rate compared with the mono-infected mice.
      Co-infection of mice with P. berghei and T. brucei resulted in rapid P. berghei
      and T. brucei development and increased parasitaemia. The leukocyte numbers
      significantly (p<0.05) reduced on days 12 and 15 post infection among P. berghei
      infected mice, in the presence or absence of T. brucei. Anaemia and hypoglycaemia
      was more severe in the co-infected mice. Therefore, co-infection of mice with P.
      berghei and T. brucei may increase pathologic impact to the host by increasing
      parasitaemia. 

PMID- 27021270
TI  - Establishment of a satellite rearing facility to support the release of sterile
      Aedes albopictus males. I. Optimization of mass rearing parameters.
AB  - The vector species Aedes albopictus (Skuse, 1894) was recorded in Turkey for the
      first time, near the Greek border, in 2011 and a high risk of expansion towards
      Aegean and Mediterranean coasts of Turkey was estimated. A preliminary study was
      planned to evaluate the possibility of creating a satellite mass rearing facility
      for this species and manage a larval rearing procedure by using the new mass
      rearing technology proposed by the International Atomic Energy Agency (IAEA). For
      this purpose, the effects of different larval densities (1, 2, 3 and 4 larvae per
      ml) on the preimaginal development were evaluated by observing pupal, adult and
      male productivity using life cycle trials. Geometric morphometric analyses were
      also performed to define all phenotypic differences that occurred on the wing
      size and shape morphology of adult stage at the four different rearing conditions
      tested. A high pupation productivity was obtained with a larval density of 2
      larvae/ml while adult emergence ratio was not affected by the densities tested.
      No significant difference was observed in shape of the wings among different
      densities in males and females. Nevertheless, a significant difference in
      female's centroid sizes was observed between the treatment groups 1-2 and 3-4
      larvae/ml and in males centroid size reared at 1 larvae/ml versus the other
      densities. 

PMID- 27021271
TI  - A charge-suppressing strategy for probing protein methylation.
AB  - Methylation of arginine and lysine (RK) residues play essential roles in
      epigenetics and the regulation of gene expression. However, research in this area
      is often hindered by the lack of effective tools for probing the protein
      methylation. Here, we present an antibody-free strategy to capture protein
      methylation on RK residues by using chemical reactions to eliminate the charges
      on un-modified RK residues and peptide N-termini. Peptides containing methylated
      RK residues remain positively charged and are then enriched by strong cation
      exchange chromatography, followed by high-resolution mass spectrometry
      identification. 

PMID- 27021273
TI  - Variability of the IFN-gamma ELISpot assay in the context of proficiency testing
      and bridging studies.
AB  - Assays that assess cellular mediated immune responses performed under Good
      Clinical Laboratory Practice (GCLP) guidelines are required to provide specific
      and reproducible results. Defined validation procedures are required to establish
      the Standard Operating Procedure (SOP), include pass and fail criteria, as well
      as implement positivity criteria. However, little to no guidance is provided on
      how to perform longitudinal assessment of the key reagents utilized in the assay.
      Through the External Quality Assurance Program Oversight Laboratory (EQAPOL), an
      Interferon-gamma (IFN-gamma) Enzyme-linked immunosorbent spot (ELISpot) assay
      proficiency testing program is administered. A limit of acceptable within site
      variability was estimated after six rounds of proficiency testing (PT).
      Previously, a PT send-out specific within site variability limit was calculated
      based on the dispersion (variance/mean) of the nine replicate wells of data. Now
      an overall 'dispersion limit' for the ELISpot PT program within site variability
      has been calculated as a dispersion of 3.3. The utility of this metric was
      assessed using a control sample to calculate the within (precision) and between
      (accuracy) experiment variability to determine if the dispersion limit could be
      applied to bridging studies (studies that assess lot-to-lot variations of key
      reagents) for comparing the accuracy of results with new lots to results with old
      lots. Finally, simulations were conducted to explore how this dispersion limit
      could provide guidance in the number of replicate wells needed for within and
      between experiment variability and the appropriate donor reactivity (number of
      antigen-specific cells) to be used for the evaluation of new reagents. Our
      bridging study simulations indicate using a minimum of six replicate wells of a
      control donor sample with reactivity of at least 150 spot forming cells per well
      is optimal. To determine significant lot-to-lot variations use the 3.3 dispersion
      limit for between and within experiment variability.

PMID- 27021272
TI  - Postprandial lipids accelerate and redirect nitric oxide consumption in plasma.
AB  - Nitric oxide (NO) and O2 are both three-to four-fold more soluble in biological
      lipids than in aqueous solutions. Their higher concentration within plasma lipids
      accelerates NO autoxidation to an extent that may be of importance to overall NO
      bioactivity. This study was undertaken to test the hypothesis that increased
      plasma lipids after a high-fat meal appreciably accelerate NO metabolism and
      alter the byproducts formed. We found that plasma collected from subjects after
      consumption of a single high-fat meal had a higher capacity for NO consumption
      and consumed NO more rapidly compared to fasting plasma. This increased NO
      consumption showed a direct correlation with plasma triglyceride concentrations
      (p = 0.006). The accelerated NO consumption in postprandial plasma was reversed
      by removal of the lipids from the plasma, was mimicked by the addition of
      hydrophobic micelles to aqueous buffer, and could not be explained by the
      presence of either free hemoglobin or ceruloplasmin. The products of NO
      consumption were shifted in postprandial plasma, with 55% more nitrite (n = 12, p
      = 0.002) but 50% less SNO (n = 12, p = 0.03) production compared to matched
      fasted plasma. Modeling calculations indicated that NO autoxidation was
      accelerated by about 48-fold in the presence of plasma lipids. We conclude that
      postprandial triglyceride-rich lipoproteins exert a significant influence on NO
      metabolism in plasma.

PMID- 27021274
TI  - The influence of Citrate or PEG coating on silver nanoparticle toxicity to a
      human keratinocyte cell line.
AB  - Surface coating of silver nanoparticles may influence their toxicity, in a way
      yet to decipher. In this study, human keratinocytes (HaCaT cells) were exposed
      for 24 and 48h to well-characterized 30nm AgNPs coated either with citrate (Cit30
      AgNPs) or with poly(ethylene glycol) (PEG30 AgNPs), and assessed for cell
      viability, reactive oxygen species (ROS), cytokine release, apoptosis and cell
      cycle dynamics. The results showed that Cit30 AgNPs and PEG30 AgNPs decreased
      cell proliferation and viability, the former being more cytotoxic. The coating
      molecules per se were not cytotoxic. Moreover, Ag(+) release and ROS production
      were similar for both AgNP types. Cit30 AgNPs clearly induced apoptotic death,
      while cells exposed to PEG30 AgNPs appeared to be at an earlier phase of
      apoptosis, supported by changes in BAX, BCL2 and CASP-3 expressions. Concerning
      the impact on cell cycle dynamics, both Cit30 and PEG30 AgNPs affected cell cycle
      regulation of HaCaT cells, but, again, citrate-coating induced more drastic
      effects, showing earlier downregulation of cyclin B1 gene and cellular arrest at
      the G2 phase. Overall, this study has shown that the surface coating of AgNPs
      influences their toxicity by differently regulating cell-cycle and cell death
      mechanisms. 

PMID- 27021277
TI  - Thrombus around the redesigned HeartWare HVAD inflow cannula: A pathologic case
      series.

PMID- 27021276
TI  - Antigen presentation events during the initiation of autoimmune diabetes in the
      NOD mouse.
AB  - This is a brief summary of our studies of NOD autoimmune diabetes examining the
      events during the initial stage of the process. Our focus has been on antigen
      presentation events and the antigen presenting cells (APC) inside islets. Islets
      of non-diabetic mice contain resident macrophages that are developmentally
      distinct from those in the inter-acinar stroma. The autoimmune process starts
      with the entrance of CD4+ T cells together with a burst of a subset of dendritic
      cells (DC) bearing CD103. The CD103+ DC develop under the influence of the Batf3
      transcription factor. Batf3 deficient mice do not develop diabetes and their
      islets are uninfiltrated throughout life. Thus, the CD103+ DC are necessary for
      the progression of autoimmune diabetes. The major CD4+ T cell response in NOD are
      the T cells directed to insulin. In particular, the non-conventional 12-20
      segment of the insulin B chain is presented by the class II MHC molecule I-A(g7)
      and elicits pathogenic CD4+ T cells. We discuss that the diabetic process
      requires the CD103+ DC, the CD4+ T cells to insulin peptides, and NOD specific I
      Ag(7) MHC-II allele. Finally, our initial studies indicate that beta cells
      transfer insulin containing vesicles to the local APC in a contact-dependent
      reaction. Live images of beta cells interactions with the APC and electron
      micrographs of islet APCs also show the transfer of granules.

PMID- 27021275
TI  - The role of the innate immune system in destruction of pancreatic beta cells in
      NOD mice and humans with type I diabetes.
AB  - Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by T
      cell-mediated destruction of the insulin-producing pancreatic beta cells. A
      combination of genetic and environmental factors eventually leads to the loss of
      functional beta cell mass and hyperglycemia. Both innate and adaptive immunity
      are involved in the development of T1D. In this review, we have highlighted the
      most recent findings on the role of innate immunity, especially the pattern
      recognition receptors (PRRs), in disease development. In murine models and human
      studies, different PRRs, such as toll-like receptors (TLRs) and nucleotide
      binding domain, leucine-rich repeat-containing (or Nod-like) receptors (NLRs),
      have different roles in the pathogenesis of T1D. These PRRs play a critical role
      in defending against infection by sensing specific ligands derived from exogenous
      microorganisms to induce innate immune responses and shape adaptive immunity.
      Animal studies have shown that TLR7, TLR9, MyD88 and NLPR3 play a disease
      predisposing role in T1D, while controversial results have been found with other
      PRRs, such as TLR2, TLR3, TLR4, TLR5 and others. Human studies also shown that
      TLR2, TLR3 and TLR4 are expressed in either islet beta cells or infiltrated
      immune cells, indicating the innate immunity plays a role in beta cell
      autoimmunity. Furthermore, some human genetic studies showed a possible
      association of TLR3, TLR7, TLR8 or NLRP3 genes, at single nucleotide polymorphism
      (SNP) level, with human T1D. Increasing evidence suggest that the innate immunity
      modulates beta cell autoimmunity. Thus, targeting pathways of innate immunity may
      provide novel therapeutic strategies to fight this disease.

PMID- 27021278
TI  - From statistical significance to clinical relevance: A simple algorithm to
      integrate brain natriuretic peptide and the Seattle Heart Failure Model for risk
      stratification in heart failure.
AB  - BACKGROUND: Heart failure (HF) guidelines recommend brain natriuretic peptide
      (BNP) and multivariable risk scores, such as the Seattle Heart Failure Model
      (SHFM), to predict risk in HF with reduced ejection fraction (HFrEF). A practical
      way to integrate information from these 2 prognostic tools is lacking. We sought
      to establish a SHFM+BNP risk-stratification algorithm. METHODS: The retrospective
      derivation cohort included consecutive patients with HFrEF at the Mayo Clinic.
      One-year outcome (death, transplantation or ventricular assist device) was
      assessed. The SHFM+BNP algorithm was derived by stratifying patients within SHFM
      predicted risk categories (<=2.5%, 2.6% to <=10%, >10%) according to BNP above or
      below 700 pg/ml and comparing SHFM-predicted and observed event rates within each
      SHFM+BNP category. The algorithm was validated in a prospective, multicenter
      HFrEF registry (Penn HF Study). RESULTS: Derivation (n = 441; 1-year event rate
      17%) and validation (n = 1,513; 1-year event rate 12%) cohorts differed with the
      former being older and more likely ischemic with worse symptoms, lower EF, worse
      renal function and higher BNP and SHFM scores. In both cohorts, across the 3 SHFM
      predicted risk strata, a BNP >700 pg/ml consistently identified patients with
      approximately 3-fold the risk that the SHFM would have otherwise estimated,
      regardless of stage of HF, intensity and duration of HF therapy and
      comorbidities. Conversely, the SHFM was appropriately calibrated in patients with
      a BNP <700 pg/ml. CONCLUSION: The simple SHFM+BNP algorithm displays stable
      performance across diverse HFrEF cohorts and may enhance risk stratification to
      enable appropriate decision-making regarding HF therapeutic or palliative
      strategies.

PMID- 27021279
TI  - Patient-reported symptoms and functioning as indicators of mortality in advanced
      cystic fibrosis: A new tool for referral and selection for lung transplantation.
AB  - BACKGROUND: Despite well-known risk factors and predictive survival models, many
      patients with cystic fibrosis (CF) die while on the waiting list for lung
      transplant. We evaluated whether specific Cystic Fibrosis Questionnaire (CFQ-R)
      scales provide additional benefit to conventional tools in identifying referral
      timing and waitlist mortality. METHODS: From January 2010 to January 2015, 152
      patients (34% on the waitlist) were evaluated with the CFQ-R and standard
      protocol quarterly. Data were used to explore the prognostic association of
      health-related quality of life. RESULTS: The Physical Functioning domain (PFD) of
      the CFQ-R predicted mortality in advanced CF disease better than habitual
      parameters (p = 0.005). For patients with the same forced expiratory volume in 1
      sec (FEV1), a low score categorized patients with an increased risk of death. For
      patients with CF and FEV1 <30% predicted and a low Physical score, mortality rate
      was ~35% at 2 years. The best model for probability of inclusion on the waitlist
      was FEV1 % (p < 0.001, hazard ratio [HR] = 0.94; 95% confidence interval [CI]
      [0.90, 0.97]) and Physical Functioning (p = 0.013, HR = 0.96; 95% CI [0.95,
      0.99]). The best model for probability of death similarly included FEV1 % (p =
      0.09, HR = 0.97; 95% CI [0.94, 1.00]) and CFQ-R Physical Functioning score (p =
      0.005, HR = 0.97; 95% CI [0.95, 0.99]). The Health Perception score showed
      similar results. A low Health Perception score combined with a high resting heart
      rate showed a trend for mortality. CONCLUSIONS: The CFQ-R may be an additional
      tool for guiding decisions to place a patient with CF on the waiting list for
      lung transplantation. The CFQ-R Physical Functioning and Health Perception scales
      were more accurate than conventional tools in predicting death before transplant.

PMID- 27021280
TI  - CircRNA-derived pseudogenes.

PMID- 27021281
TI  - Benzothiazole hydrazones of furylbenzamides preferentially stabilize c-MYC and c
      KIT1 promoter G-quadruplex DNAs.
AB  - The stabilization of G-quadruplex DNA structures by using small molecule ligands
      having simple structural scaffolds has the potential to be harnessed for
      developing next generation anticancer agents. Because of the structural diversity
      of G-quadruplexes, it is challenging to design stabilizing ligands, which can
      specifically bind to a particular quadruplex topology. To address this, herein,
      we report the design and synthesis of three benzothiazole hydrazones of
      furylbenzamides having different side chains (ligands 1, 2 and 3), which show
      preferential stabilization of promoter quadruplex DNAs (c-MYC and c-KIT1) having
      parallel topologies over telomeric and duplex DNAs. The CD melting study revealed
      that all the ligands, in particular ligand 2, exhibit higher stabilization toward
      parallel promoter quadruplexes (DeltaTm = 10-15  degrees C) as compared to
      antiparallel promoter quadruplex (h-RAS1), telomeric quadruplex and duplex DNAs
      (DeltaTm = 0-3  degrees C). FID assay and fluorimetric titration results also
      reveal the preferential binding of ligands toward c-MYC and c-KIT1 promoter
      quadruplex DNAs over telomeric and duplex DNAs. Validating these results further,
      Taq DNA polymerase stop assay showed IC50~ 6.4 MUM for ligand 2 with the c-MYC
      DNA template, whereas the same for the telomeric DNA template was found to be
      >200 MUM. Molecular modeling and dynamics studies demonstrated a 1 : 1 binding
      stoichiometry in which stacking and electrostatic interactions play important
      roles in stabilizing the c-MYC G-quadruplex structure. Taken together, the
      results presented here provide new insights into the design of structurally
      simple scaffolds for the preferential stabilization of a particular G-quadruplex
      topology. 

PMID- 27021282
TI  - Distal biceps ruptures: open and endoscopic techniques.
AB  - Distal biceps tendon ruptures are relatively rare. Patients are usually middle
      aged men involved in heavy labor. Patients usually present with the history of a
      pop and a proximal migration of the biceps muscle belly. Clinical exam should be
      sufficient to diagnose a complete rupture. Several specific tests have been
      described. Ultrasound scanning or MRI can help confirm the diagnosis. Radiographs
      are not needed to diagnose distal biceps tendon rupture but may show typical
      findings. Imaging, more specifically the flexion-abduction-supination (FABS) view
      MRI, is particularly helpful in the case of a partial rupture or chronic rupture
      of the distal biceps tendon. Results of surgical reinsertion of the distal biceps
      have been shown to be superior to conservative treatment. Different techniques
      and approaches have been described with specific advantages and disadvantages.
      Primary repair of the tendon is preferred. If this is no longer possible in
      chronic tears, an augmentation can be done using tendon graft. Results of
      surgical treatment are good in the vast majority of patients. Reruptures are rare
      but minor complications are common. Major complications may include posterior
      interosseous nerve palsy or radioulnar synostosis, but the risk of these
      complications may be decreased by meticulous attention to detail during surgery. 

PMID- 27021283
TI  - Mesolimbic confidence signals guide perceptual learning in the absence of
      external feedback.
AB  - It is well established that learning can occur without external feedback, yet
      normative reinforcement learning theories have difficulties explaining such
      instances of learning. Here, we propose that human observers are capable of
      generating their own feedback signals by monitoring internal decision variables.
      We investigated this hypothesis in a visual perceptual learning task using fMRI
      and confidence reports as a measure for this monitoring process. Employing a
      novel computational model in which learning is guided by confidence-based
      reinforcement signals, we found that mesolimbic brain areas encoded both
      anticipation and prediction error of confidence-in remarkable similarity to
      previous findings for external reward-based feedback. We demonstrate that the
      model accounts for choice and confidence reports and show that the mesolimbic
      confidence prediction error modulation derived through the model predicts
      individual learning success. These results provide a mechanistic neurobiological
      explanation for learning without external feedback by augmenting reinforcement
      models with confidence-based feedback. 

PMID- 27021284
TI  - The NAC transcription factor ANAC046 is a positive regulator of chlorophyll
      degradation and senescence in Arabidopsis leaves.
AB  - Chlorophyll (Chl) degradation occurs during leaf senescence, embryo degreening,
      bud breaking, and fruit ripening. The Chl catabolic pathway has been intensively
      studied and nearly all the enzymes involved are identified and characterized;
      however, the molecular regulatory mechanisms of this pathway are largely unknown.
      In this study, we performed yeast one-hybrid screening using a transcription
      factor cDNA library to search for factors controlling the expression of Chl
      catabolic genes. We identified ANAC046 as a common regulator that directly binds
      to the promoter regions of NON-YELLOW COLORING1, STAY-GREEN1 (SGR1), SGR2, and
      PHEOPHORBIDE a OXYGENASE. Transgenic plants overexpressing ANAC046 exhibited an
      early-senescence phenotype and a lower Chl content in comparison with the wild
      type plants, whereas loss-of-function mutants exhibited a delayed-senescence
      phenotype and a higher Chl content. Microarray analysis of ANAC046 transgenic
      plants showed that not only Chl catabolic genes but also senescence-associated
      genes were positively regulated by ANAC046. We conclude that ANAC046 is a
      positive regulator of Arabidopsis leaf senescence and exerts its effect by
      controlling the expression of Chl catabolic genes and senescence-associated
      genes. 

PMID- 27021285
TI  - Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma
      aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.
AB  - gamma-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters
      in the central nervous system. It has multiple positive effects on mammalian
      physiology and is an important bioactive component of tea (Camellia sinensis).
      GABA generally occurs at a very low level in plants but GABA content increases
      substantially after exposure to a range of stresses, especially oxygen
      deficiency. During processing of tea leaves, a combination of anoxic stress and
      mechanical damage are essential for the high accumulation of GABA. This is
      believed to be initiated by a change in glutamate decarboxylase activity, but the
      underlying mechanisms are unclear. In the present study we characterized factors
      regulating the expression and activity of three tea glutamate decarboxylase genes
      (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike
      the model plant Arabidopsis thaliana, there are dual mechanisms regulating the
      accumulation of GABA in tea leaves exposed to multiple stresses, including
      activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the
      stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of
      anoxic stress and mechanical damage. 

PMID- 27021286
TI  - The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk
      Factors in Indonesia.
AB  - BACKGROUND: In Indonesia, coronary heart disease (CHD) and stroke are estimated
      to cause more than 470 000 deaths annually. In order to inform primary prevention
      policies, we estimated the sex- and age-specific burden of CHD and stroke
      attributable to five major and modifiable vascular risk factors: cigarette
      smoking, hypertension, diabetes, elevated total cholesterol, and excess body
      weight. METHODS: Population attributable risks for CHD and stroke attributable to
      these risk factors individually were calculated using summary statistics obtained
      for prevalence of each risk factor specific to sex and to two age categories (<55
      and >=55 years) from a national survey in Indonesia. Age- and sex-specific
      relative risks for CHD and stroke associated with each of the five risk factors
      were derived from prospective data from the Asia-Pacific region. RESULTS:
      Hypertension was the leading vascular risk factor, explaining 20%-25% of all CHD
      and 36%-42% of all strokes in both sexes and approximately one-third of all CHD
      and half of all strokes across younger and older age groups alike. Smoking in men
      explained a substantial proportion of vascular events (25% of CHD and 17% of
      strokes). However, given that these risk factors are likely to be strongly
      correlated, these population attributable risk proportions are likely to be
      overestimates and require verification from future studies that are able to take
      into account correlation between risk factors. CONCLUSIONS: Implementation of
      effective population-based prevention strategies aimed at reducing levels of
      major cardiovascular risk factors, especially blood pressure, total cholesterol,
      and smoking prevalence among men, could reduce the growing burden of CVD in the
      Indonesian population.

PMID- 27021287
TI  - Clinical decision support systems: great promises for better management of
      patients' drug therapy.

PMID- 27021289
TI  - Emergency point-of-care ultrasound in Canadian pediatric emergency fellowship
      programs: current integration and future directions.
AB  - BACKGROUND: Adult and pediatric emergency physicians have been using point-of
      care ultrasound (POCUS) for many years. It is a fast, usually painless,
      noninvasive diagnostic tool that does not expose the patient to radiation.
      Information about its current implementation in pediatric emergency medicine
      (PEM) fellowship programs in Canada is lacking. OBJECTIVE: The main goal of our
      study was to investigate current integration and future direction of POCUS
      training in Canadian PEM programs. METHODS: The study consisted of two surveys
      designed for fellows and program directors of all Canadian PEM fellowship
      programs. The major aspects of the survey were 1) to describe current training in
      POCUS in fellowship programs, 2) to compare the kind of training that programs
      offer with what fellows actually receive, and 3) a needs assessment by fellows
      and program directors for future POCUS training programs. Surveys were sent to
      program directors and passed on to their fellows. RESULTS: Ninety percent of
      fellowship program directors as well as 70% (42/60) of fellows responded to the
      survey. A formal POCUS curriculum exists in five of the nine PEM programs
      included in this study. Three programs offer specific pediatric POCUS training.
      The main application is the FAST (focused assessment with sonography for trauma)
      exam. CONCLUSION: There is a wide variation in POCUS content and delivery across
      PEM fellowship programs, as well as differences in perceptions of current
      training and of needs by fellows and program directors. However, given that both
      groups feel POCUS is very important and essential for PEM training, the
      opportunity exists to develop a standardized curriculum across Canada.

PMID- 27021288
TI  - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity
      disorder.
AB  - Aggressiveness is a behavioral trait that has the potential to be harmful to
      individuals and society. With an estimated heritability of about 40%, genetics is
      important in its development. We performed an exploratory genome-wide association
      (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity
      disorder (ADHD) to gain insight into the underlying biological processes
      associated with this trait. Our primary sample consisted of 1,060 adult ADHD
      patients (aADHD). To further explore the genetic architecture of childhood
      aggressiveness, we performed enrichment analyses of suggestive genome-wide
      associations observed in aADHD among GWA signals of dimensions of oppositionality
      (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No
      single polymorphism reached genome-wide significance (P < 5.00E-08). The
      strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA
      gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed
      by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The
      top GWA SNPs observed in aADHD showed significant enrichment of signals from both
      the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable
      dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a
      number of biologically interesting markers possibly underlying childhood
      aggressiveness and provide targets for further genetic exploration of
      aggressiveness across psychiatric disorders. (c) 2016 The Authors. American
      Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley
      Periodicals, Inc.

PMID- 27021290
TI  - Intractable bleeding tendency due to acquired von Willebrand syndrome after
      Jarvik 2000 implant.
AB  - A 61-year-old man was implanted with a Jarvik 2000, a continuous axial flow type
      left ventricular assist device (LVAD), for end-stage heart failure due to dilated
      cardiomyopathy. One month later, his postoperative course was complicated with
      intractable oozing-type gastrointestinal bleeding from multiple small shallow
      ulcers and erosions in the colon. In addition, repeated bleeding episodes were
      encountered at around thoracentesis site for pleural effusion. Hematological
      examination showed that platelet counts and coagulation factors were kept within
      normal ranges. We, thereafter, revealed remarkable loss of the large multimers of
      von Willebrand factors (VWFs), which might be closely associated with his
      intractable bleeding tendency. 

PMID- 27021291
TI  - Clinical,biochemical and molecular analysis of five Chinese patients with
      Sandhoff disease.
AB  - Sandhoff disease (SD) is a rare autosomal recessive lysosomal storage disorder of
      sphingolipid metabolism resulting from the deficiency of beta-hexosaminidase
      (HEX). Mutations of the HEXB gene cause Sandhoff disease. In order to improve the
      diagnosis and expand the knowledge of the disease, we collected and analyzed
      relevant data of clinical diagnosis, biochemical investigation, and molecular
      mutational analysis in five Chinese patients with SD. The patients presented with
      heterogenous symptoms of neurologic deterioration. HEX activity in leukocytes was
      severely deficient. We identified seven different mutations, including three
      known mutations: IVS12-26G > A, p.T209I, p.I207V, and four novel mutations:
      p.P468PfsX62, p.L223P, p.Y463X, p.G549R. We also detected two different
      heterozygous mutations c.-122delC and c.-126C > T in the promoter which were
      suspected to be deleterious mutations. We attempted to correlate these mutations
      with the clinical presentation of the patients. Our study indicates that the
      mutation p.T209I and p.P468PfsX62 may link to the infantile form of SD. Our study
      expands the spectrum of genotype of SD in China, provides new insights into the
      molecular mechanism of SD and helps to the diagnosis and treatment of this
      disease.

PMID- 27021292
TI  - Chronic methamphetamine exposure prior to middle cerebral artery occlusion
      increases infarct volume and worsens cognitive injury in Male mice.
AB  - Emerging evidence indicates that methamphetamine (MA) abuse can impact
      cardiovascular disease. In humans, MA abuse is associated with an increased risk
      of stroke as well as an earlier age at which the stroke occurs. However, little
      is known about how chronic daily MA exposure can impact ischemic outcome in
      either humans or animal models. In the present study, mice were injected with MA
      (10 mg/kg, i.p.) or saline once daily for 10 consecutive days. Twenty-four hours
      after the final injection, mice were subjected to transient middle cerebral
      artery occlusion (tMCAO) for one hour followed by reperfusion. Mice were tested
      for novel object memory at 96 h post-reperfusion, just prior to removal of brains
      for quantification of infarct volume using 2,3,5-Triphenyltetrazolium Chloride
      (TTC) staining. Mice treated with MA prior to tMCAO showed decreased object
      memory recognition and increased infarct volume compared to saline-treated mice.
      These findings indicate that chronic MA exposure can worsen both cognitive and
      morphological outcomes following cerebral ischemia.

PMID- 27021293
TI  - Is 60 the New 80 in Hypertension?
AB  - Since the release of the "2014 evidence-based guideline for the management of
      high blood pressure in adults: report from the panel members appointed to the
      Eighth Joint National Committee (JNC 8)", much controversy has ensued over the
      appropriate systolic blood pressure goal for those over the age of 60 years. This
      guideline suggested liberalizing the target for this population to <150 mmHg,
      moving away from previous guidelines suggesting a target of <140 mmHg. While some
      national quality measures have accepted the new relaxed blood pressure goal, the
      American Heart Association and American College of Cardiology have not. Recently
      published data show that millions of adults over 60 years of age would be
      classified as controlled using a threshold of <150 mmHg, but not with a target of
      <140 mmHg. In addition, emerging randomized trial evidence suggests that
      targeting a systolic blood pressure well below 140 mmHg is beneficial in older
      adults. In light of the improved health and vitality of older adults, and the
      steady decline in cardiovascular and cerebrovascular mortality over recent
      decades, we do not think it is in good judgment to liberalize the treatment
      target in adults less than 80 years of age.

PMID- 27021294
TI  - Implementation Science Workshop: a Novel Multidisciplinary Primary Care Program
      to Improve Care and Outcomes for Super-Utilizers.

PMID- 27021295
TI  - Microelectromechanical reprogrammable logic device.
AB  - In modern computing, the Boolean logic operations are set by interconnect schemes
      between the transistors. As the miniaturization in the component level to enhance
      the computational power is rapidly approaching physical limits, alternative
      computing methods are vigorously pursued. One of the desired aspects in the
      future computing approaches is the provision for hardware reconfigurability at
      run time to allow enhanced functionality. Here we demonstrate a reprogrammable
      logic device based on the electrothermal frequency modulation scheme of a single
      microelectromechanical resonator, capable of performing all the fundamental 2-bit
      logic functions as well as n-bit logic operations. Logic functions are performed
      by actively tuning the linear resonance frequency of the resonator operated at
      room temperature and under modest vacuum conditions, reprogrammable by the a.c.
      driving frequency. The device is fabricated using complementary metal oxide
      semiconductor compatible mass fabrication process, suitable for on-chip
      integration, and promises an alternative electromechanical computing scheme. 

PMID- 27021297
TI  - Giant left anterior descending coronary artery aneurysm in an adult male patient
      with ST elevation myocardial infarction.
AB  - Coronary artery aneurysm is a rare clinical entity encountered incidentally 0.3
      5% among patients who undergo coronary angiography. Even giant coronary artery
      aneurysm is much rarer with an incidence of 0.02% among all atherosclerotic
      cases. Due to rare occurrence and lack of controlled trials, clinical
      presentation, prognosis and management of giant coronary artery aneurysm are
      under controversies in the literature. We report a 43-year-old male patient
      admitted to our hospital with a typical chest pain associated with ST elevation
      changes in anterior chest leads and elevated cardiac enzymes. Coronary
      angiography of the patient revealed a large (1.5 cm * 3 cm) aneurysm of proximal
      left anterior descending coronary artery. We performed a successful surgical
      excision and coronary bypass surgery. The patient had an uncomplicated course. 

PMID- 27021298
TI  - Speciation of metal phosphonates with the assistance of weak interactions.
AB  - By employing an aromatic methyl substituted V-shaped diphosphonic acid as a
      ligand, a series of metal diphosphonates, namely [Cu3(HL)2(H2O)2][(H2O)2] (1),
      [Cu(H2L)(pyz)(H2O)2][(H2O)2] (2), [Cu(H2L)(2,2'-bipy)] (3), [Cu(H2L)(4,4'
      bipy)(H2O)2] (4), [Zn(H2L)(2,2'-bipy)] (5) and [Cd(H2L)(2,2'-bipy)(H2O)][(H2O)6]
      (6), have been synthesized. The structural studies reveal that these compounds
      exhibit diverse crystal structures. The introduction of the methyl group and
      pyridine derived auxiliary ligands results in the formation of plenty of C-HO, C
      Hpi and pipi interactions, which contribute to the crystallization of metal
      diphosphonates. It was found that the Zn and Cd containing compounds showed
      intense intraligand emissions.

PMID- 27021296
TI  - CCR5+T-bet+FoxP3+ Effector CD4 T Cells Drive Atherosclerosis.
AB  - RATIONALE: CD4 T cells are involved in the pathogenesis of atherosclerosis, but
      atherosclerosis-specific CD4 T cells have not been described. Moreover, the
      chemokine(s) that regulates T-cell trafficking to the atherosclerotic lesions is
      also unknown. OBJECTIVE: In Apoe(-/-) mice with mature atherosclerotic lesions (5
      months of high fat diet), we find that most aortic T cells express CCR5 and
      interferon-gamma with a unique combination of cell surface markers (CD4(+)CD25(
      )CD44(hi)CD62L(lo)) and transcription factors (FoxP3(+)T-bet(+)). We call these
      cells CCR5Teff. We investigated the role of CCR5 in regulating T-cell homing to
      the atherosclerotic aorta and the functionality of the CCR5Teff cells. METHODS
      AND RESULTS: CCR5Teff cells are exclusively found in the aorta and para-aortic
      lymph nodes of Apoe(-/-) mice. They do not suppress T-cell proliferation in vitro
      and are less potent than regulatory T cells at inhibiting cytokine secretion.
      Blocking or knocking out CCR5 or its ligand CCL5 significantly blocks T-cell
      homing to atherosclerotic aortas. Transcriptomic analysis shows that CCR5Teff
      cells are more similar to effector T cells than to regulatory T cells. They
      secrete interferon-gamma, interleukin-2, interleukin-10, and tumor necrosis
      factor. Adoptive transfer of these CCR5Teff cells significantly increases
      atherosclerosis. CONCLUSIONS: CCR5 is specifically needed for CD4 T-cell homing
      to the atherosclerotic plaques. CCR5(+)CD4 T cells express an unusual combination
      of transcription factors, FoxP3 and T-bet. Although CCR5Teff express FoxP3, we
      showed that they are not regulatory and adoptive transfer of these cells
      exacerbates atherosclerosis.

PMID- 27021299
TI  - Superficial middle cerebral vein connection to the cavernous sinus is not
      infrequent in brain arteriovenous malformations: an argument against their
      congenital origin?
AB  - INTRODUCTION: The aim of this study was to test the hypothesis that the
      superficial middle cerebral vein (SMCV) is frequently absent or fails to connect
      with the cavernous sinus (CS) in the presence of brain arteriovenous
      malformations (AVMs), a frequently reported argument for the congenital origin of
      brain AVMs. METHODS: The SMCV was retrospectively compared between patients with
      a brain AVM and a control group. The presence or absence of the SMCV, its direct
      or indirect connection to the CS and its termination in a laterocavernous sinus
      (LCS), paracavernous sinus (PCS), or directly in the CS was studied on digital
      subtraction angiography. RESULTS: One hundred twenty-five left or right side
      carotid angiograms from 70 patients with a brain AVM were compared to 125
      angiograms from 74 controls. The SMCV was present in 88 (70.4 %) cases in the
      brain AVM group and 96 (76.8 %) cases in controls (p = 0.25). The SMCV was
      connected directly or indirectly to the CS in 65 (52 %) cases in the brain AVM
      group and 65 (52 %) cases in controls (p = 1). When comparing the subgroup of
      carotid angiograms ipsilateral to a supratentorial AVM, no statistically
      significant difference was found with controls. In three of six cases in which a
      SMCV drained an AVM, the vein terminated directly or indirectly in the CS.
      CONCLUSIONS: No difference of SMCV presence and direct or indirect connection to
      the CS was found between patients with AVM and a control group. SMCV anatomy does
      not support the congenital origin of brain AVMs.

PMID- 27021300
TI  - Genotyping of 22 blood group antigen polymorphisms and establishing a national
      recipient registry in the Korean population.
AB  - It is often difficult for standard blood banks in Korea to supply adequate
      amounts of blood for patients with rare phenotype. Moreover, the definition of a
      blood in need is ambiguous, and much remains to be learned. In this study, we
      determined the prevalence of various red blood cell (RBC) antigens from a donor
      viewpoint and estimated the demand for specific antigen-negative blood from a
      patient viewpoint. Our data will aid the establishment of a Rare Blood Program in
      Korea (KRBP). RBC genotyping of 419 blood donors was performed using a Lifecodes
      RBC/RBC-R typing kit (Immucor, Norcross, GA). A national recipient registry
      website has been established. Each hospital-based blood bank voluntarily enters
      data on antibodies detected and identified and the outcomes of specific antigen
      testing. We calculated the availabilities of specific antigen-negative blood
      components based on these registry data and predicted the prevalence of RBC
      antigens via RBC genotyping. The prevalences of various RBC antigens in the D
      negative population were determined for the first time, and the Cartwright,
      Scianna, Dombrock, Colton, Landsteiner-Wiener, Cromer, and Knops blood group
      systems were identified. The availabilities of specific antigen-negative units
      differed when calculations were based on serotyping or genotyping, especially in
      the D-negative group. Data on the prevalences of various blood antigens are
      essential for estimating the availabilities of blood components that are
      appropriate for use by patients expressing relevant antibodies. Then, blood banks
      would be able to efficiently supply safe blood products. 

PMID- 27021301
TI  - Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis
      in febrile neutropenia.
AB  - Azole prophylaxis has been shown to be effective in preventing invasive fungal
      infections (IFIs) and increasing survival in patients with prolonged neutropenia
      after myelosuppressive chemotherapy for haematological malignancies. Similarly,
      empirical antifungal therapy for persistent neutropenic fever has been shown to
      reduce IFI-related mortality. However, to date, there is little information with
      regard to the outcome of patients who receive both strategies. Here, we present
      our retrospective data on three cohorts of patients receiving empirical or
      targeted antifungal therapy after different antifungal prophylaxis regimens. All
      records from patients who received myelosuppressive induction chemotherapy for
      acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From
      2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6
      months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of
      315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy
      (empirical or targeted, time point and antifungal agent at the physician's
      discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %,
      p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the
      posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and
      22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %),
      4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related
      survival was not different in the three cohorts. Antifungal treatment in patients
      with AML who received azole prophylaxis resulted in the expected efficacy
      importantly, prior posaconazole prophylaxis did not render subsequent antifungal
      treatment less effective than prior itraconazole prophylaxis. 

PMID- 27021302
TI  - Unusual co-occurrence of Hodgkin lymphoma and hemophagocytic lymphohistiocytosis
      in a bone marrow aspirate.

PMID- 27021303
TI  - Allogeneic hematopoietic cell transplantation in patients with myelofibrosis: A
      single center experience.
AB  - Myelofibrosis (MF) is a rare disease responsible for an increasing ineffective
      hematopoesis by a progressive fibrosing process in the bone marrow. The only
      curative treatment option is allogeneic hematopoietic cell transplantation (HCT).
      In this single-center analysis, we evaluated retrospectively 54 consecutive
      patients suffering from primary or secondary MF which underwent HCT from 1997 to
      2014 after either myeloablative (MAC, n = 19) or reduced-intensity conditioning
      (RIC, n = 35). Overall survival (OS) and disease-free survival (DFS) after 3
      years was 54/53 % for RIC versus 63/58 % for MAC (p = 0.8/0.97). Cumulative
      incidence of relapse was 34 % after RIC and 8 % after MAC (p = 0.16). Three-year
      non-relapse mortality (NRM) was 15 % after RIC and 34 % after MAC (p = 0.29). We
      found that RIC was associated with a lower incidence of acute graft versus host
      disease (GvHD; II-IV 26 vs. 0 %, p = 0.004). Evaluation of prognostic relevance
      of the Dynamic International Prognostic Scoring System (DIPSS) score showed a
      significant better OS in patient with risk score <=3 versus >3 (after 3 years, 71
      vs. 39 %, p = 0.008). While similar OS and DFS were observed with MAC or RIC, the
      use of RIC resulted in lower incidence of acute GvHD. RIC regimens may be
      therefore the preferred conditioning approach for allogeneic HCT in patients with
      MF. 

PMID- 27021304
TI  - Safety of pembrolizumab after allogeneic haematopoietic stem cell
      transplantation.

PMID- 27021305
TI  - Altered treatment of chronic lymphocytic leukemia in Germany during the last
      decade.
AB  - Chronic lymphocytic leukemia (CLL) is the most common subtype of adult leukemia
      in the western world. We here report a nationwide survey monitoring the treatment
      decisions concerning CLL patients in Germany in 2011 and compare treatment trends
      to sequential surveys performed previously during the last decade. The rate of
      patients diagnosed in early stages (Binet A/B) notably increased (2006: 66 %,
      2009: 71 %, 2011: 77 %) over the years. From 2006 to 2009, the most frequent
      applied regime switched from chlorambucil to fludarabine containing regimes (2006
      chlorambucil: 32 %, 2009: 14 %, fludarabine 2006: 23 %, 2009: 37 %). In 2011, the
      combination of rituximab with bendamustine (31 %) was most frequent used followed
      by the rituximab-fludarabine-cyclophosphamide (22 %) regime. Further, immune
      chemotherapies were administered significantly more often over the observation
      period (2006: 15 %, 2011: 73 %). Taken together, this data reflects the change of
      treatment strategies over the last decade in clinical reality. 

PMID- 27021306
TI  - Psychosis and Substance Use: Implications for Conditional Release Readiness
      Evaluations.
AB  - In Foucha v. Louisiana (1992), the United States Supreme Court ruled that
      individuals adjudicated not guilty by reason of insanity (NGRI) could not remain
      in a forensic hospital if they were no longer mentally ill and dangerous. Since
      this decision, a variety of important questions have arisen related to the
      insanity defense and what should happen to insanity acquittees post-adjudication.
      This article provides an analysis of clinical issues confronting forensic
      examiners when psychosis as a result of substance abuse is the underlying
      condition supporting an insanity defense. To accomplish this analysis, this
      article provides the reader with a review of literature showing the complex
      relationship between psychosis and substance abuse. Second, this article
      investigates how substance-induced psychosis may impact both insanity opinions
      and subsequent conditional release decisions. Third, the article aims to provide
      research-driven information to assist clinicians in conducting conditional
      release evaluations. Finally, this paper provides a model for evaluating
      dangerousness in the context of conditional release evaluations. Given the
      substantial comorbidity between substance abuse and psychosis, it is critical for
      researchers and clinicians to consider potential effects of substance abuse when
      evaluating insanity acquittees for conditional release, especially as substance
      use relates to future dangerousness. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27021307
TI  - Toward a microbial Neolithic revolution in buildings.
AB  - The Neolithic revolution--the transition of our species from hunter and gatherer
      to cultivator--began approximately 14,000 years ago and is essentially complete
      for macroscopic food. Humans remain largely pre-Neolithic in our relationship
      with microbes but starting with the gut we continue our hundred-year project of
      approaching the ability to assess and cultivate benign microbiomes in our bodies.
      Buildings are analogous to the body and it is time to ask what it means to
      cultivate benign microbiomes in our built environment. A critical distinction is
      that we have not found, or invented, niches in buildings where healthful
      microbial metabolism occurs and/or could be cultivated. Key events affecting the
      health and healthfulness of buildings such as a hurricane leading to a flood or a
      burst pipe occur only rarely and unpredictably. The cause may be transient but
      the effects can be long lasting and, e.g., for moisture damage, cumulative. Non
      invasive "building tomography" could find moisture and "sentinel microbes" could
      record the integral of transient growth. "Seed" microbes are metabolically inert
      cells able to grow when conditions allow. All microbes and their residue present
      actinic molecules including immunological epitopes (molecular shapes). The
      fascinating hygiene and microbial biodiversity hypotheses propose that a healthy
      immune system requires exposure to a set of microbial epitopes that is rich in
      diversity. A particular conjecture is that measures of the richness of diversity
      derived from microbiome next-generation sequencing (NGS) can be mechanistically
      coupled to--rather than merely correlated with some measures of--human health.
      These hypotheses and conjectures inspire workers and funders but an alternative
      is also consequent to the first Neolithic revolution: That the genetic uniformity
      of contemporary foods may also decrease human exposure to molecular biodiversity
      in a heath-relevant manner. Understanding the consequences--including the
      unintended consequences of the first Neolithic revolution--will inform and help
      us benignly implement the second--the microbial--Neolithic revolution.

PMID- 27021308
TI  - Chimeric antigen receptor-modified T cells strike back.
AB  - Chimeric antigen receptors (CARs) are engineered molecules designed to endow a
      polyclonal T-cell population with the ability to recognize tumor-associated
      surface antigens. In their simplest form, CARs comprise a targeting moiety in the
      form of a single-chain variable fragment from an antibody connected to various
      intracellular signaling domains allowing for T-cell activation. This powerful
      approach combines the specificity of an antibody with the cytotoxic ability of a
      T cell. There has been much excitement since early phase trials of CAR-T cells
      targeting CD19 expressed on B-cell malignancies demonstrated remarkable efficacy
      in inducing long-term, stable remissions in otherwise relapsed/refractory
      disease. Despite these successes, we have just begun to understand the
      intricacies of CAR biology with efforts underway to utilize this platform in the
      treatment of other, previously refractory malignancies. Challenges currently
      include identification of viable cancer targets, management strategies for
      potentially severe and irreversible toxicities and overcoming the
      immunosuppressive nature of the tumor microenvironment. This review will focus on
      basic CAR structure and function, previous success and new approaches aimed at
      the broader application of CAR-T-cell therapy.

PMID- 27021309
TI  - Sphingosine Kinases: Emerging Structure-Function Insights.
AB  - Sphingosine kinases (SK1 and SK2) catalyse the conversion of sphingosine into
      sphingosine 1-phosphate and control fundamental cellular processes, including
      cell survival, proliferation, differentiation, migration, and immune function. In
      this review, we highlight recent breakthroughs in the structural and functional
      characterisation of SK1 and these are contextualised by analysis of crystal
      structures for closely related prokaryotic lipid kinases. We identify a putative
      dimerisation interface and propose novel regulatory mechanisms governing
      structural plasticity induced by phosphorylation and interaction with
      phospholipids and proteins. Our analysis suggests that the catalytic function and
      regulation of the enzymes might be dependent on conformational mobility and it
      provides a roadmap for future interrogation of SK1 function and its role in
      physiology and disease.

PMID- 27021310
TI  - Divorce and Childhood Chronic Illness: A Grounded Theory of Trust, Gender, and
      Third-Party Care Providers.
AB  - Divorced parents face distinct challenges in providing care for chronically ill
      children. Children's residence in two households necessitates the development of
      family-specific strategies to ensure coparents' supervision of regimen adherence
      and the management of children's health care. Utilizing a risk and resilience
      perspective, a grounded theory study was conducted with 14 divorced parents of
      children with chronic illnesses. The importance of trust, gender, and
      relationships with third-party care providers emerged as key themes related to
      the development of effective coparenting relationships for maintaining children's
      health. Divorced parents were best able to support the management of their
      children's chronic conditions when care providers operated as neutral third
      parties and intermediaries. Collaborative family care may require health care
      practitioners to avoid being drawn into contentious inter-parental conflicts.

PMID- 27021311
TI  - Design and synthesis of 2,3-dihydro- and 5-chloro-2,3-dihydro-naphtho-[1,2
      b]furan-2-carboxylic acid N-(substitutedphenyl)amide analogs and their biological
      activities as inhibitors of NF-kappaB activity and anticancer agents.
AB  - A series of 2,3-dihydro- and 5-chloro-2,3-dihydro-naphtho-[1,2-b]furan-2
      carboxylic acid N-(substitutedphenyl)amide analogs (1a-k and 2a-i) were designed
      and synthesized for developing novel naphthofuran scaffolds as anticancer agents
      and inhibitors of NF-kappaB activity. Compound 1d, which had a 4'-chloro group on
      the N-phenyl ring, exhibited inhibitory activity of NF-kappaB. Compound 2g, which
      had a 5'-chloro group on the naphthofuran ring and a 3',5'-bistrifluoromethane
      group on the N-phenyl ring, had the best NF-kappaB inhibitory activity. In
      addition, the novel analogs exhibited potent cytotoxicity at low concentrations
      against HCT-116, NCI-H23, and PC-3 cell lines. The two electron-withdrawing
      groups, especially at the 3',5'-position on the N-phenyl ring, increased
      anticancer activity and NF-kappaB inhibitory activity. However, only 5-chloro-2,3
      dihydronaphtho[1,2-b]furan-2-carboxylic N-(3',5'-bis(trifluoromethyl)phenyl)amide
      (2g) exhibited both outstanding cytotoxicity and NF-kappaB inhibitory activities.
      This novel lead scaffold may be helpful for investigation of new anticancer
      agents by inactivation of NF-kappaB. 

PMID- 27021312
TI  - Susceptibility to disease varies with ontogeny and immunocompetence in a
      threatened amphibian.
AB  - Ontogenetic changes in disease susceptibility have been demonstrated in many
      vertebrate taxa, as immature immune systems and limited prior exposure to
      pathogens can place less developed juveniles at a greater disease risk. By
      causing the disease chytridiomycosis, Batrachochytrium dendrobatidis (Bd)
      infection has led to the decline of many amphibian species. Despite increasing
      knowledge on how Bd varies in its effects among species, little is known on the
      interaction between susceptibility and development within host species. We
      compared the ontogenetic susceptibility of post-metamorphic green and golden bell
      frogs Litoria aurea to chytridiomycosis by simultaneously measuring three host
      pathogen responses as indicators of the development of the fungus-infection load,
      survival rate, and host immunocompetence-following Bd exposure in three life
      stages (recently metamorphosed juveniles, subadults, adults) over 95 days. Frogs
      exposed to Bd as recently metamorphosed juveniles acquired higher infection loads
      and experienced lower immune function and lower survivorship than subadults and
      adults, indicating an ontogenetic decline in chytridiomycosis susceptibility. By
      corresponding with an intrinsic developmental maturation in immunocompetence seen
      in uninfected frogs, we suggest these developmental changes in host
      susceptibility in L. aurea may be immune mediated. Consequently, the
      physiological relationship between ontogeny and immunity may affect host
      population structure and demography through variation in life stage survival, and
      understanding this can shape management targets for effective amphibian
      conservation.

PMID- 27021313
TI  - A Replicative In Vitro Assay for Drug Discovery against Leishmania donovani.
AB  - The protozoan parasite Leishmania donovani is the causative agent of visceral
      leishmaniasis, a disease potentially fatal if not treated. Current available
      treatments have major limitations, and new and safer drugs are urgently needed.
      In recent years, advances in high-throughput screening technologies have enabled
      the screening of millions of compounds to identify new antileishmanial agents.
      However, most of the compounds identified in vitro did not translate their
      activities when tested in in vivo models, highlighting the need to develop more
      predictive in vitro assays. In the present work, we describe the development of a
      robust replicative, high-content, in vitro intracellular L. donovani assay. Horse
      serum was included in the assay media to replace standard fetal bovine serum, to
      completely eliminate the extracellular parasites derived from the infection
      process. A novel phenotypic in vitro infection model has been developed,
      complemented with the identification of the proliferation of intracellular
      amastigotes measured by EdU incorporation. In vitro and in vivo results for
      miltefosine, amphotericin B, and the selected compound 1 have been included to
      validate the assay.

PMID- 27021314
TI  - Evaluating the Effects of Surotomycin Treatment on Clostridium difficile Toxin A
      and B Production, Immune Response, and Morphological Changes.
AB  - Surotomycin is a cyclic lipopeptide in development for Clostridium difficile
      associated diarrhea. This study aimed to assess the impact of surotomycin
      exposure on C. difficile toxin A and B concentrations and the associated changes
      in immune response in comparison to vancomycin and metronidazole. Time-kill curve
      assays were performed using strain R20291 (BI/NAP1/027) at supra-MICs (4* and
      40*) and sub-MICs (0.5*) of surotomycin and comparators. Following treatment, CFU
      counts, toxin A and B concentrations, and cellular morphological changes using
      scanning electron microscopy were examined. Inflammatory response was determined
      by measuring interleukin-8 (IL-8) concentrations from polarized Caco-2 cells
      exposed to antibiotic-treated C. difficile growth media. Supra-MICs (4* and 40*)
      of surotomycin resulted in a reduction of vegetative cells over 72 h (4-log
      difference, P < 0.01) compared to controls. These results correlated with
      decreases of 77% and 68% in toxin A and B production at 48 h, respectively (P <
      0.005, each), which resulted in a significant reduction in IL-8 concentration
      compared to controls. Similar results were observed with comparator antibiotics.
      Bacterial cell morphology showed that the cell wall was broken apart by
      surotomycin treatment at supra-MICs while sub-MIC studies showed a "deflated"
      phenotype plus a rippling effect. These results suggest that surotomycin has
      potent killing effects on C. difficile that results in reduced toxin production
      and attenuates the immune response similar to comparator antibiotics. The
      morphological data also confirm observations that surotomycin is a membrane
      active antibiotic.

PMID- 27021315
TI  - Hepatitis C Virus RNA-Dependent RNA Polymerase Interacts with the Akt/PKB Kinase
      and Induces Its Subcellular Relocalization.
AB  - Hepatitis C virus (HCV) interacts with cellular components and modulates their
      activities for its own benefit. These interactions have been postulated as a
      target for antiviral treatment, and some candidate molecules are currently in
      clinical trials. The multifunctional cellular kinase Akt/protein kinase B (PKB)
      must be activated to increase the efficacy of HCV entry but is rapidly
      inactivated as the viral replication cycle progresses. Viral components have been
      postulated to be responsible for Akt/PKB inactivation, but the underlying
      mechanism remained elusive. In this study, we show that HCV polymerase NS5B
      interacts with Akt/PKB. In the presence of transiently expressed NS5B or in
      replicon- or virus-infected cells, NS5B changes the cellular localization of
      Akt/PKB from the cytoplasm to the perinuclear region. Sequestration of Akt/PKB by
      NS5B could explain its exclusion from its participation in early Akt/PKB
      inactivation. The NS5B-Akt/PKB interaction represents a new regulatory step in
      the HCV infection cycle, opening possibilities for new therapeutic options.

PMID- 27021316
TI  - The LABCG2 Transporter from the Protozoan Parasite Leishmania Is Involved in
      Antimony Resistance.
AB  - Treatment for leishmaniasis, which is caused by Leishmania protozoan parasites,
      currently relies on a reduced arsenal of drugs. However, the significant increase
      in the incidence of drug therapeutic failure and the growing resistance to first
      line drugs like antimonials in some areas of Northern India and Nepal limit the
      control of this parasitic disease. Understanding the molecular mechanisms of
      resistance in Leishmania is now a matter of urgency to optimize drugs used and to
      identify novel drug targets to block or reverse resistant mechanisms. Some
      members of the family of ATP-binding cassette (ABC) transporters in Leishmania
      have been associated with drug resistance. In this study, we have focused our
      interest to characterize LABCG2's involvement in drug resistance in Leishmania.
      Leishmania major parasites overexpressing the ABC protein transporter LABCG2 were
      generated in order to assess how LABCG2 is involved in drug resistance. Assays of
      susceptibility to different leishmanicidal agents were carried out. Analysis of
      the drug resistance profile revealed that Leishmania parasites overexpressing
      LABCG2 were resistant to antimony, as they demonstrated a reduced accumulation of
      Sb(III) due to an increase in drug efflux. Additionally, LABCG2 was able to
      transport thiols in the presence of Sb(III) Biotinylation assays using parasites
      expressing LABCG2 fused with an N-terminal green fluorescent protein tag revealed
      that LABCG2 is partially localized in the plasma membrane; this supports data
      from previous studies which suggested that LABCG2 is localized in intracellular
      vesicles that fuse with the plasma membrane during exocytosis. In conclusion,
      Leishmania LABCG2 probably confers antimony resistance by sequestering metal
      thiol conjugates within vesicles and through further exocytosis by means of the
      parasite's flagellar pocket.

PMID- 27021317
TI  - High Intracellular Concentrations of Posaconazole Do Not Impact on Functional
      Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived
      Macrophages In Vitro.
AB  - Posaconazole is a commonly used antifungal for the prophylaxis and treatment of
      invasive fungal infections. We previously demonstrated that the intracellular
      concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and
      polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma
      concentration. As these professional phagocytes are crucial to combat fungal
      infections, we set out to investigate if and how, beneficial or deleterious, this
      high loading of intracellular posaconazole impacts the functional capacities of
      these cells. Here, we show that high intracellular concentrations of posaconazole
      do not significantly impact PMN and monocyte-derived macrophage function in vitro
      In particular, killing capacity and cytoskeletal features of PMN, such as
      migration, are not affected, indicating that these cells serve as vehicles for
      posaconazole to the site of infection. Moreover, since posaconazole as such
      slowed the germination of Aspergillus fumigatus conidia, infected neutrophils
      released less reactive oxygen species (ROS). Based on these findings, we propose
      that the delivery of posaconazole by neutrophils to the site of Aspergillus
      species infection warrants control of the pathogen and preservation of tissue
      integrity at the same time.

PMID- 27021318
TI  - Rapid Flow Cytometry Test for Identification of Different Carbapenemases in
      Enterobacteriaceae.
AB  - A flow cytometry test was developed to identify carbapenemase production by
      Enterobacteriaceae and to discriminate between the different types of
      carbapenemases (classes A, B, and D). It is based on the detection of meropenem
      activity against bacteria, coupled with different carbapenemase inhibitors, which
      is assessed by flow cytometry. It represents a convenient, fast, and reliable
      approach (100% sensitivity and 100% specificity) for the detection and
      characterization of different carbapenemases.

PMID- 27021319
TI  - Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting
      the AmgRS Envelope Stress-Responsive Two-Component System.
AB  - A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5
      linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified
      the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5
      linked AGs, such as neomycin and ribostamycin, but not the clinically important
      4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant
      lacking the AmgRS envelope stress response two-component system (TCS), which
      protects the organism from AG-generated membrane-damaging aberrant polypeptides
      and, thus, promotes AG resistance, an indication that RIF was acting via this TCS
      in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF
      resistant RNA polymerase mutant, consistent with its potentiation of AG activity
      being dependent on RNA polymerase perturbation. PAR-inducible expression of the
      AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG
      activation of this TCS was compromised by this agent. Still, RIF did not
      compromise the membrane-protective activity of AmgRS, an indication that it
      impacted some other function of this TCS. RIF potentiated the activities of 4,5
      linked AGs against several AG-resistant clinical isolates, in two cases also
      potentiating the activity of the 4,6-linked AGs. These cases were, in one
      instance, explained by an observed AmgRS-dependent expression of the MexXY
      multidrug efflux system, which accommodates a range of AGs, with RIF targeting of
      AmgRS undermining mexXY expression and its promotion of resistance to 4,5- and
      4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG
      resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment
      of P. aeruginosa infections.

PMID- 27021320
TI  - Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1
      Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State.
AB  - Clofazimine (CFZ) is a poorly soluble antibiotic and anti-inflammatory drug
      indicated for the treatment of leprosy. In spite of its therapeutic value, CFZ
      therapy is accompanied by the formation of drug biocrystals that accumulate
      within resident tissue macrophages, without obvious toxicological manifestations.
      Therefore, to specifically elucidate the off-target consequences of drug
      bioaccumulation in macrophages, we compared the level of inflammasome activation
      in CFZ-accumulating organs (spleen, liver and lung) in mice after 2 and 8 weeks
      of CFZ treatment when the drug exists in soluble and insoluble (biocrystalline)
      forms, respectively. Surprisingly, the results showed a drastic reduction in
      caspase 1 and interleukin-1beta (IL-1beta) cleavage in the livers of mice treated
      with CFZ for 8 weeks (8-week-CFZ-treated mice) compared to 2-week-CFZ-treated and
      control mice, which was accompanied by a 3-fold increase in hepatic IL-1 receptor
      antagonist (IL-1RA) production and a 21-fold increase in serum IL-1RA levels. In
      the lung and spleen, IL-1beta cleavage and tumor necrosis factor alpha expression
      were unaffected by soluble or biocrystal CFZ forms. Functionally, there was a
      drastic reduction of carrageenan- and lipopolysaccharide-induced inflammation in
      the footpads and lungs, respectively, of 8-week-CFZ-treated mice. This
      immunomodulatory activity of CFZ biocrystal accumulation was attributable to the
      upregulation of IL-1RA, since CFZ accumulation had minimal effect in IL-1RA
      knockout mice or 2-week-CFZ-treated mice. In conclusion, CFZ accumulation and
      biocrystal formation in resident tissue macrophages profoundly altered the host's
      immune system and prompted an IL-1RA-dependent, systemic anti-inflammatory
      response.

PMID- 27021321
TI  - Efficacy of Artilysin Art-175 against Resistant and Persistent Acinetobacter
      baumannii.
AB  - Bacteriophage-encoded endolysins have shown promise as a novel class of
      antibacterials with a unique mode of action, i.e., peptidoglycan degradation.
      However, Gram-negative pathogens are generally not susceptible due to their
      protective outer membrane. Artilysins overcome this barrier. Artilysins are
      optimized, engineered fusions of selected endolysins with specific outer membrane
      destabilizing peptides. Artilysin Art-175 comprises a modified variant of
      endolysin KZ144 with an N-terminal fusion to SMAP-29. Previously, we have shown
      the high susceptibility of Pseudomonas aeruginosa to Art-175. Here, we report
      that Art-175 is highly bactericidal against stationary-phase cells of multidrug
      resistant Acinetobacter baumannii, even resulting in a complete elimination of
      large inocula (>=10(8) CFU/ml). Besides actively dividing cells, Art-175 also
      kills persisters. Instantaneous killing of A. baumannii upon contact with Art-175
      could be visualized after immobilization of the bacteria in a microfluidic flow
      cell. Effective killing of a cell takes place through osmotic lysis after
      peptidoglycan degradation. The killing rate is enhanced by the addition of 0.5 mM
      EDTA. No development of resistance to Art-175 under selection pressure and no
      cross-resistance with existing resistance mechanisms could be observed. In
      conclusion, Art-175 represents a highly active Artilysin against both A.
      baumannii and P. aeruginosa, two of the most life-threatening pathogens of the
      order Pseudomonadales.

PMID- 27021322
TI  - Analysis of beta-Lactamase Resistance Determinants in Enterobacteriaceae from
      Chicago Children: a Multicenter Survey.
AB  - Multidrug-resistant (MDR) Enterobacteriaceae infections are increasing in U.S.
      children; however, there is a paucity of multicentered analyses of antibiotic
      resistance genes responsible for MDR phenotypes among pediatric
      Enterobacteriaceae isolates. In this study, 225 isolates phenotypically
      identified as extended-spectrum beta-lactamase (ESBL) or carbapenemase producers,
      recovered from children ages 0 to 18 years hospitalized between January 2011 and
      April 2015 at three Chicago area hospitals, were analyzed. We used DNA microarray
      platforms to detect ESBL, plasmid-mediated AmpC (pAmpC), and carbapenemase type
      beta-lactamase (bla) genes. Repetitive-sequence-based PCR and multilocus sequence
      typing (MLST) were performed to assess isolate similarity. Plasmid replicon
      typing was conducted to classify plasmids. The median patient age was 4.2 years,
      56% were female, and 44% presented in the outpatient setting. The majority
      (60.9%) of isolates were Escherichia coli and from urinary sources (69.8%). Of
      225 isolates exhibiting ESBL- or carbapenemase-producing phenotypes, 90.7%
      contained a bla gene. The most common genotype was the blaCTX-M-1 group (49.8%);
      1.8% were carbapenem-resistant Enterobacteriaceae (three blaKPC and one blaIMP).
      Overall, pAmpC (blaACT/MIR and blaCMY) were present in 14.2%. The predominant E.
      coli phylogenetic group was the virulent B2 group (67.6%) associated with
      ST43/ST131 (Pasteur/Achtman MLST scheme) containing the blaCTX-M-1 group (84%),
      and plasmid replicon types FIA, FII, and FIB. K. pneumoniae harboring blaKPC were
      non-ST258 with replicon types I1 and A/C. Enterobacter spp. carrying blaACT/MIR
      contained plasmid replicon FIIA. We found that beta-lactam resistance in children
      is diverse and that certain resistance mechanisms differ from known circulating
      genotypes in adults in an endemic area. The potential impact of complex molecular
      types and the silent dissemination of MDR Enterobacteriaceae in a vulnerable
      population needs to be studied further.

PMID- 27021323
TI  - Biofilm Production and Antibiofilm Activity of Echinocandins and Liposomal
      Amphotericin B in Echinocandin-Resistant Yeast Species.
AB  - The echinocandins and liposomal amphotericin B are active against biofilm
      produced by echinocandin-susceptible Candida strains. However, few data have been
      reported on the production of biofilm by echinocandin-resistant isolates and
      their antifungal susceptibility. We studied the production of biofilm by fks
      mutant Candida strains and intrinsically echinocandin-resistant non-Candida
      isolates and the susceptibility of both entities to liposomal amphotericin B and
      echinocandins. We analyzed the production of biofilm by isolates from patients
      with fungemia (fks mutant Candida, n = 5; intrinsically echinocandin-resistant
      non-Candida, n = 12; and Candida wild type, n = 10). Biofilm formation was
      measured to classify strains according to biomass (crystal violet assay) and
      metabolic activity (XTT reduction assay). Preformed biofilms were tested against
      liposomal amphotericin B, caspofungin, micafungin, and anidulafungin. The sessile
      MIC was defined as the antifungal concentration yielding a 50% or 80% reduction
      in the metabolic activity of the biofilm compared to that of the growth control
      (SMIC50 and SMIC80, respectively). fks mutant Candida isolates formed biofilms in
      a fashion similar to that of Candida wild-type strains. The echinocandins had the
      highest activity against biofilms formed by wild-type Candida isolates, followed
      by fks mutant Candida isolates and non-Candida isolates. Liposomal amphotericin B
      had the highest activity against fks mutant Candida biofilms. The formation of
      biofilm by echinocandin-resistant strains was similar to that of wild-type
      strains, although resistance to echinocandins remained high.

PMID- 27021324
TI  - Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and
      without Cystic Fibrosis.
AB  - Invasive fungal infections (IFIs) are common among lung transplant recipients
      (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and
      treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs,
      particularly those with cystic fibrosis (CF). Our objective was to conduct a
      pharmacokinetic study of posaconazole oral suspension among LTRs, with particular
      attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other
      underlying lung diseases. Average daily doses in CF and non-CF patients were 829
      and 862 mg, respectively. After >=5 days of treatment, only 4 patients had
      average plasma concentrations of >0.7 MUg/ml. Average steady-state plasma
      concentrations were 61% lower in CF patients (0.233 MUg/ml) than in non-CF LTRs
      (0.594 MUg/ml; P = 0.03). The average dose-normalized plasma area-under-the-curve
      (AUC) values were also lower in CF (0.007 h.MUg/ml) than in non-CF LTRs (0.02
      h.MUg/ml; P = 0.02). The weight-normalized apparent oral clearance values were
      2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (P = 0.005).
      Despite significant interpatient variability, plasma trough concentrations were
      strongly correlated with posaconazole AUC across all LTRs (r(2) = 0.95, P <
      0.0001). Taken together, our study highlights a critical need to incorporate new
      formulations of posaconazole into prophylaxis and treatment strategies for LTRs,
      particularly those with CF. Future pharmacokinetic studies of both tablet and
      intravenous formulations must consider LTR-specific factors and incorporate a
      therapeutic drug monitoring plan in this patient population.

PMID- 27021325
TI  - Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with
      Acute Kidney Injury Treated with Continuous Renal Replacement Therapy.
AB  - The objective of this study was to describe the pharmacokinetics of cefotaxime
      (CTX) in critically ill patients with acute kidney injury (AKI) when treated with
      continuous renal replacement therapy (CRRT) in the intensive care unit (ICU).
      This single-center prospective observational pilot study was performed among ICU
      patients with AKI receiving >=48 h concomitant CRRT and CTX. CTX was administered
      intravenously 1,000 mg (bolus) every 6 h for 4 days. CRRT was performed as
      continuous venovenous hemofiltration (CVVH). Plasma concentrations of CTX and its
      active metabolite desacetylcefotaxime (DAC) were measured during CVVH treatment.
      CTX plasma levels and patient data were used to construct concentration-time
      curves. By using this data, the duration of plasma levels above 4 mg/liter (four
      times the MIC) was calculated and analyzed. Twenty-seven patients were included.
      The median CTX peak level was 55 mg/liter (range, 19 to 98 mg/liter), the median
      CTX trough level was 12 mg/liter (range, 0.8 to 37 mg/liter), and the median DAC
      plasma level was 15 mg/liter (range, 1.5 to 48 mg/liter). Five patients (19%) had
      CTX plasma levels below 4 mg/liter at certain time points during treatment. In at
      least 83% of the time any patient was treated with CTX, the CTX plasma level
      stayed above 4 mg/liter. A dosing regimen of 1,000 mg of CTX given four times
      daily is likely to achieve adequate plasma levels in patients with AKI treated
      with CVVH. Dose reduction might be a risk for suboptimal treatment.

PMID- 27021326
TI  - Activity of Fusidic Acid Tested against Staphylococci Isolated from Patients in
      U.S. Medical Centers in 2014.
AB  - Fusidic acid (FA) activity was evaluated against 2,002 clinical staphylococcal
      isolates collected in U.S. hospitals during 2014. FA (MIC50/90, 0.12/0.12 MUg/ml)
      inhibited 99.8% of Staphylococcus aureus isolates at <=1 MUg/ml. Only four S.
      aureus isolates displayed FA values of >2 MUg/ml (three strains with fusC and one
      with an L461K substitution in fusA), and they were isolated from patients in four
      states. In conclusion, FA demonstrated sustained, potent activity against this
      recent collection of U.S. staphylococci.

PMID- 27021327
TI  - dfrA thyA Double Deletion in para-Aminosalicylic Acid-Resistant Mycobacterium
      tuberculosis Beijing Strains.

PMID- 27021328
TI  - Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action
      Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida
      spp.
AB  - The incidence of fungal infections and, in particular, the incidence of fungal
      antibiotic resistance, which is associated with biofilm formation, have
      significantly increased, contributing to morbidity and mortality. Thus, new
      therapeutic strategies need to be developed. In this context, natural products
      have emerged as a major source of possible antifungal agents. Berberine is a
      protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and
      stem bark of natural herbs, such as Berberis aquifolium, Berberis vulgaris,
      Berberis aristata, and Hydrastis canadensis, and of Phellodendron amurense
      Berberine has been proven to have broad antibacterial and antifungal activity. In
      the present study, the potential antifungal effect of berberine against
      fluconazole-resistant Candida and Cryptococcus neoformans strains, as well as
      against the biofilm form of Candida spp., was assessed. The antifungal effect of
      berberine was determined by a broth microdilution method (the M27-A3 method of
      the Clinical and Laboratory Standards Institute) and flow cytometry techniques,
      in which the probable mechanism of action of the compound was also assessed. For
      biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) assay was used to determine the susceptibility of
      sessile cells. The isolates used in the study belonged to the Laboratory of
      Bioprospection and Experiments in Yeast (LABEL) of the Federal University of
      Ceara. After 24 and 72 h, fluconazole-resistant Candida and Cryptococcus
      neoformans strains showed berberine MICs equal to 8 MUg/ml and 16 MUg/ml,
      respectively. Cytometric analysis showed that treatment with berberine caused
      alterations to the integrity of the plasma and mitochondrial membranes and DNA
      damage, which led to cell death, probably by apoptosis. Assessment of biofilm
      forming isolates after treatment showed statistically significant reductions in
      biofilm cell activity (P < 0.001).

PMID- 27021329
TI  - Antitubercular Agent Delamanid and Metabolites as Substrates and Inhibitors of
      ABC and Solute Carrier Transporters.
AB  - Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of
      nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant
      tuberculosis. Patients with tuberculosis require treatment with multiple drugs,
      several of which have known drug-drug interactions. Transporters regulate drug
      absorption, distribution, and excretion; therefore, the inhibition of transport
      by one agent may alter the pharmacokinetics of another, leading to unexpected
      adverse events. Therefore, it is important to understand how delamanid affects
      transport activity. In the present study, the potencies of delamanid and its main
      metabolites as the substrates and inhibitors of various transporters were
      evaluated in vitro Delamanid was not transported by the efflux ATP-binding
      cassette (ABC) transporters P-glycoprotein (P-gp; MDR1/ABCB1) and breast cancer
      resistance protein (BCRP/ABCG2), solute carrier (SLC) transporters, organic anion
      transporting polypeptides, or organic cation transporter 1. Similarly, metabolite
      1 (M1) was not a substrate for any of these transporters except P-gp. Delamanid
      showed no inhibitory effect on ABC transporters MDR1, BCRP, and bile salt export
      pump (BSEP; ABCB11), SLC transporters, or organic anion transporters. M1 and M2
      inhibited P-gp- and BCRP-mediated transport but did so only at the 50% inhibitory
      concentrations (M1, 4.65 and 5.71 MUmol/liter, respectively; M2, 7.80 and 6.02
      MUmol/liter, respectively), well above the corresponding maximum concentration in
      plasma values observed following the administration of multiple doses in clinical
      trials. M3 and M4 did not affect the activities of any of the transporters
      tested. These in vitro data suggest that delamanid is unlikely to have clinically
      relevant interactions with drugs for which absorption and disposition are
      mediated by this group of transporters.

PMID- 27021330
TI  - Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro
      Selection, Fitness, and Resistance Patterns in the Context of the Infectious
      Viral Life Cycle.
AB  - Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of
      novel HCV therapy regimens. Studies of PI resistance initially focused on
      genotype 1. Therefore, knowledge about the determinants of PI resistance for the
      highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture
      infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified
      protease positions 54, 155, and 156 as hot spots for the selection of resistance
      substitutions under treatment with the first licensed PIs, telaprevir and
      boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir,
      faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified
      positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged
      for three newer PIs. Substitution selection also depended on the specific
      recombinant. The substitutions identified conferred cross-resistance to several
      PIs; however, most substitutions selected under telaprevir or boceprevir
      treatment conferred less resistance to certain newer PIs. In a single-cycle
      production assay, across genotypes, PI treatment primarily decreased viral
      replication, which was rescued by PI resistance substitutions. The substitutions
      identified resulted in differential effects on viral fitness, depending on the
      original recombinant and the substitution. Across genotypes, fitness impairment
      induced by resistance substitutions was due primarily to decreased replication.
      Most combinations of substitutions that were identified increased resistance or
      fitness. Combinations of resistance substitutions with fitness-compensating
      substitutions either rescued replication or compensated for decreased replication
      by increasing assembly. This comprehensive study provides insight into the
      selection patterns and effects of PI resistance substitutions for HCV genotypes 1
      to 6 in the context of the infectious viral life cycle, which is of interest for
      clinical and virological HCV research.

PMID- 27021332
TI  - Improvement of the Xpert Carba-R Kit for the Detection of Carbapenemase-Producing
      Enterobacteriaceae.
AB  - The Xpert Carba-R kit, version 2 (v2), which has been improved for the efficient
      detection of blaOXA-181 and blaOXA-232 genes, was tested on a collection of 150
      well-characterized enterobacterial isolates that had a reduced susceptibility to
      carbapenems. The performance of the Xpert Carba-R v2 was high, as it was able to
      detect the five major carbapenemases (NDM, VIM, IMP, KPC, and OXA-48). Thus, it
      is now well adapted to the carbapenemase-producing Enterobacteriaceae
      epidemiology of many countries worldwide.

PMID- 27021331
TI  - Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and
      Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against
      Candida albicans.
AB  - Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] activates the yeast cell wall
      integrity pathway. Candida albicans exposure to caspofungin results in the rapid
      redistribution of PI(4,5)P2 and septins to plasma membrane foci and subsequent
      fungicidal effects. We studied C. albicans PI(4,5)P2 and septin dynamics and
      protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following
      exposure to caspofungin and other drugs. PI(4,5)P2 and septins were visualized by
      live imaging of C. albicans cells coexpressing green fluorescent protein (GFP)
      pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively.
      PI(4,5)P2 was also visualized in GFP-PH domain-expressing C. albicans mkc1
      mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway
      activation. Fungicidal activity was assessed using 20-h time-kill assays.
      Caspofungin immediately induced PI(4,5)P2 and Cdc10p colocalization to aberrant
      foci, a process that was highly dynamic over 3 h. PI(4,5)P2 levels increased in a
      dose-response manner at caspofungin concentrations of <=4* MIC and progressively
      decreased at concentrations of >=8* MIC. Caspofungin exposure resulted in broad
      based mother-daughter bud necks and arrested septum-like structures, in which
      PI(4,5)P2 and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within
      10 min, peaked in response to caspofungin at 4* MIC, and declined at higher
      concentrations. The caspofungin-induced PI(4,5)P2 redistribution remained
      apparent in mkc1 mutants. Caspofungin exerted dose-dependent killing and
      paradoxical effects at <=4* and >=8* MIC, respectively. Fluconazole, amphotericin
      B, calcofluor white, and H2O2 did not impact the PI(4,5)P2 or Cdc10p distribution
      like caspofungin did. Caspofungin exerts rapid PI(4,5)P2-septin and PKC-Mkc1
      responses that correlate with the extent of C. albicans killing, and the
      responses are not induced by other antifungal agents. PI(4,5)P2-septin regulation
      is crucial in early caspofungin responses and PKC-Mkc1 activation.

PMID- 27021334
TI  - Poor agreement of objectively measured and self-reported physical activity in
      juvenile dermatomyositis and juvenile systemic lupus erythematosus.
AB  - To examine the agreement and association between objectively measured and
      indirectly assessed physical activity levels in patients with juvenile
      dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE) patients.
      The sample consisted of 19 JDM patients (age 8 to 22 years) and 20 JSLE patients
      (age 9 to 18 years). Physical activity level was objectively measured using
      Actigraph(r) accelerometers and indirectly assessed by the short-form
      International Physical Activity Questionnaire (IPAQ). Spearman's correlation
      coefficients were calculated to test possible associations between physical
      activity levels across the two instruments. The Bland-Altman technique was used
      to calculate bias and limits of agreement. Correlations between objectively
      measured and indirectly assessed physical activity levels in JDM and JSLE were
      weak, varying from R = 0.03 to R = 0.33 (all p > 0.05). Total physical activity
      was correlated between accelerometer and IPAQ in JSLE (R = 0.51, p = 0.021).
      Bland-Altman analyses suggested that IPAQ tended to highly underestimate
      sedentary time and light physical activity in JDM (mean bias 105.7 and 199.8 min,
      respectively) and JSLE (mean bias 36.4 and 127.8 min, respectively). Mean biases
      of moderate-to-vigorous physical activity were also highly variable, ranging from
      -42.9 to 54.9 min and -59.4 to 89.8 min for JDM and JSLE, respectively. IPAQ was
      shown to not be valid to assess physical activity levels in patients with JDM and
      JSLE when compared against accelerometry. While the validation of reliable self
      reported instruments that measure physical activity in pediatric rheumatic
      patients remains necessary, the use of validated tools that objectively measure
      physical activity is recommended in both clinical and research settings. 

PMID- 27021333
TI  - Association between atrial fibrillation, anticoagulation, risk of cerebrovascular
      events and multimorbidity in general practice: a registry-based study.
AB  - BACKGROUND: To date, there has been no comprehensive study on the association
      between atrial fibrillation (AF) and multimorbidity. The present study
      investigated the epidemiology of AF and the association between multimorbidity
      and the onset of AF. In addition, the correlation between multimorbidity and the
      use of anticoagulants and the risk of cerebrovascular events considering
      multimorbidity was explored in AF patients. METHODS: Intego is a primary care
      registry network in Belgium. A case-control study was performed using Intego data
      from a 10-year time interval (2002 to 2011). All patients aged 60 years and older
      in 2002 who had developed new AF between 2002 and 2011 were selected, as well as
      a group of matched control patients. In addition, the prescription of
      anticoagulants and incident cerebrovascular events were recorded in patients with
      AF. RESULTS: AF showed a prevalence of 5.3 % in 2002, and an upward trend was
      observed between 2002 and 2011. In all, 1830 patients with AF and 6622 control
      patients were included. AF patients had significantly more comorbidities (mCCI
      (modified Charlson Comorbidity Index) 5 +/- 2 vs 4 +/- 2, P < 0.001). In
      addition, 9.7 % of patients with AF developed a cerebrovascular event (mean
      follow-up time of 2.7 +/- 2.5 years). Both the under- and overuse of
      anticoagulants was observed. Of the 49 % of patients with AF who were considered
      at high risk (CHADS2 >= 2), 50 % received anticoagulants in the first six months
      after diagnosis, whereas 49 % of patients who were at low risk (CHADS2 = 0) did
      not. CONCLUSIONS: AF is highly prevalent in older primary care patients and is
      significantly associated with multimorbidity. A discrepancy between the
      guidelines and clinical practice of anticoagulant use was observed. As
      multimorbidity seems to play a role in this, further qualitative research to
      study the perception and motives of the general practitioner is needed.

PMID- 27021335
TI  - Genetic association study of systemic lupus erythematosus and disease
      subphenotypes in European populations.
AB  - Epidemiological studies suggest a strong contribution of genetic factors in the
      pathogenesis of systemic lupus erythematosus (SLE). In the last decades, many
      risk loci have been identified in several genetic association studies following
      both candidate gene and genome-wide approaches. The present work was conducted by
      GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium with a dual
      aim: to replicate the association of several previously reported SLE
      susceptibility loci in an independent European sample and to explore their
      relation with some disease subphenotypes. A total of 48 single nucleotide
      polymorphisms (SNP) from 40 associated loci were typed in a cohort of 208 SLE
      patients and 152 controls from Rheumatology Units of the University Hospital of
      Pisa (Italy) and University of Pecs Medical Center (Hungary). Regression analyses
      were performed to detect disease susceptibility loci and to identify genes
      affecting specific disease manifestations (renal, neurological, or skin
      involvement; arthritis; secondary Sjogren syndrome; and secondary
      antiphospholipid syndrome). Association of previously described risk alleles from
      HLA locus has been replicated, while IRF5, BLK, ITGAM, and IRF8 loci have been
      found to be consistent with previous published results. In addition, two new
      subphenotype-specific associations have been detected: SNP rs5754217 (UBE2L3)
      with skin involvement and rs3093030 (ICAM1-ICAM4-ICAM5) with hematological
      disorders. Overall, results from GAPAID project are consistent with previously
      established associations for HLA, IRF5, BLK, ITGAM, and IRF8 SLE susceptibility
      loci and report for the first time two subphenotype-specific associations. 

PMID- 27021336
TI  - Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic
      arthritis (JIA) responding to two treatment periods with exclusive enteral
      nutrition (EEN).
AB  - The microbiome and immune system of the digestive tract are highly important in
      both health and disease. Exclusive enteral nutrition (EEN) is a common anti
      inflammatory treatment in children with Crohn's disease in the European
      countries, and the mechanism is most likely linked to changes in the intestinal
      microbiome. In the present study, EEN was given in two treatment periods several
      months apart to a patient with very severe, disabling juvenile idiopathic
      arthritis (JIA), with a remarkable clinical response as the result. The aim of
      the present study was to study how the EEN treatment influenced the microbiome
      and metabolome of this patient. Fecal samples from before, during, and between
      treatments with EEN were studied. The microbiome was analyzed by sequencing of
      16S rRNA amplicons using Illumina MiSeq, and the metabolome was analyzed using
      nuclear magnetic resonance. The microbiome changed markedly from treatment with
      EEN, with a strong reduction of the Bacteroidetes phylum. Metabolic profiles
      showed clear differences before, during, and between treatment with EEN, where
      butyrate, propionate, and acetate followed a cyclic pattern with the lowest
      levels at the end of each treatment period. This patient with JIA showed
      remarkable clinical improvement after EEN treatment, and we found corresponding
      changes in both the fecal microbiome and the metabolome. Further studies are
      needed to explore the pathophysiological role of the intestinal canal in children
      with JIA. 

PMID- 27021337
TI  - Association between IL17A and IL17F polymorphisms and risk of Henoch-Schonlein
      purpura in Chinese children.
AB  - Previous studies suggested that interleukin-17 and Th17 cell play an important
      role in the pathogenesis of childhood Henoch-Schonlein purpura (HSP). The purpose
      of our study is to elucidate whether the IL17A and IL17F gene polymorphisms are
      susceptibility genes for the development of HSP in Chinese children. A total of
      148 HSP patients and 202 controls were enrolled for analyzing the single
      nucleotide polymorphisms (SNP) of IL17A (rs2275913, rs8193037 and rs3819025) and
      IL17F (rs763780 and rs9463772). TaqMan Real-Time polymerase chain reaction method
      was used in SNP genotyping. Compared to the healthy controls, the IL17A rs2275913
      variant allele A showed a significant association with HSP [odds ratio (OR) 0.70;
      95 % CI 0.51-0.94, P = 0.018]. Genotyping analysis demonstrated rs2275913 was
      associated with a decreased HSP risk (G/A vs. G/G: OR 0.56; 95 % CI 0.33-0.95;
      A/A vs. G/G: OR 0.46; 95 % CI 0.24-0.86; P = 0.032). Also, our findings showed
      that the A allele of IL17A rs3819025 was associated with a higher risk of HSP
      nephritis (OR 1.61; 95 % CI 1.00-2.58; P = 0.047). In addition, a risk haplotype
      of IL17A (GGA) was found (OR 1.84; 95 % CI 1.17-2.88; P = 0.008). However, no
      significant differences between HSP patients and healthy controls were observed
      when comparing genotype, allele or haplotype frequencies of the IL17F rs763780
      and rs9463772 polymorphisms. In this study, we confirmed that the rs2275913
      polymorphism of the IL17A gene was associated with susceptibility to HSP in
      Chinese children. However, there was no relationship between IL17F rs763780 and
      rs9463772 polymorphisms and HSP susceptibility. 

PMID- 27021338
TI  - Dramatic improvement of anti-SS-A/Ro-associated interstitial lung disease after
      immunosuppressive treatment.
AB  - The aim of the study was to report three patients affected by interstitial lung
      disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic
      improvement after immunosuppressive treatment. Medical charts were reviewed to
      obtain clinical data, laboratory parameters, lung function tests, high-resolution
      computed tomography results and response to immunosuppressive treatment. The
      three patients showed a clinical picture of a lung-dominant connective tissue
      disease characterized by a sudden onset with dyspnea, cough and subtle
      extrathoracic features together with positive anti-SS-A/Ro antibody and weak
      titer antinuclear antibodies. All three patients responded favorably to
      immunosuppressive therapy: Two cases were treated with a combination of
      corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the
      third patient, clinical benefit was obtained after rituximab was added to
      corticosteroid and immunosuppressant drug. In spite of an abrupt onset with
      significant lung function impairment, all three patients had a favorable clinical
      response to immunosuppressive therapy. This report may be useful in making
      therapeutic decisions in case of interstitial lung disease associated with anti
      SS-A antibody. 

PMID- 27021339
TI  - Characteristics, rates, and trends of melanoma incidence among Hispanics in the
      USA.
AB  - PURPOSE: The purpose of this study is to describe the epidemiology of melanoma
      among Hispanics using data that cover nearly 100 % of the US population. METHODS:
      The study used population-based cancer incidence data from the National Program
      of Cancer Registries and the Surveillance, Epidemiology and End Results Program
      to examine melanoma incidence rates and trends among Hispanics by sex, age, race,
      histology, anatomic location, stage, and tumor thickness. RESULTS: From 2008 to
      2012, 6,623 cases of melanoma were diagnosed among Hispanics. Rates were higher
      among males (4.6) than among females (4.0), but females younger than age 55 had
      higher rates than males. The most common histologic subtype was superficial
      spreading melanoma (23 %). Melanomas with poorer outcomes, such as nodular (NM)
      and acral lentiginous melanoma (ALM), were more common among males. Hispanic
      females had the highest proportion of melanoma on the lower limb and hip (33.7
      %), while Hispanic males had the highest proportion on the trunk (29.9 %).
      Incidence rates for later-stage diagnosis and thicker tumors were significantly
      higher among Hispanic men than among women. Incidence rates decreased
      significantly during 2003-2012 (AAPC = -1.4). CONCLUSIONS: Clinicians and public
      health practitioners will need to reach the growing Hispanic population in the
      USA with strategies for primary prevention and early diagnosis of melanoma.
      Results suggest Hispanics and providers need education to increase awareness
      about the characteristics of melanoma among Hispanics, including types that occur
      on non-sun-exposed areas (ALM and NM). Skin cancer prevention and awareness
      interventions targeting Hispanics should be culturally relevant.

PMID- 27021340
TI  - Altered brain activation and functional connectivity in working memory related
      networks in patients with type 2 diabetes: An ICA-based analysis.
AB  - Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits,
      among which working memory (WM) is usually involved at an early stage. However,
      the neural substrates underlying impaired WM in T2DM patients are still unclear.
      To clarify this issue, we utilized functional magnetic resonance imaging (fMRI)
      and independent component analysis to evaluate T2DM patients for alterations in
      brain activation and functional connectivity (FC) in WM networks and to determine
      their associations with cognitive and clinical variables. Twenty complication
      free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI
      data were acquired during a block-designed 1-back WM task. The WM metrics of the
      T2DM patients showed no differences compared with those of the HCs, except for a
      slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the
      T2DM patients demonstrated increased activation within their WM fronto-parietal
      networks, and activation strength was significantly correlated with WM
      performance. The T2DM patients also showed decreased FC within and between their
      WM networks. Our results indicate that the functional integration of WM sub
      networks was disrupted in the complication-free T2DM patients and that
      strengthened regional activity in fronto-parietal networks may compensate for the
      WM impairment caused by T2DM. 

PMID- 27021341
TI  - Dolutegravir monotherapy in HIV-infected patients with sustained viral
      suppression.
AB  - OBJECTIVES: We reviewed the 24 week outcomes of HIV-infected patients from our
      hospital who had their ART switched to dolutegravir monotherapy on an individual
      clinical basis. METHODS: Retrospective hospital database assessment of virally
      suppressed patients in whom the treating physician had switched to 50 mg of
      dolutegravir once daily due to one or more of the following reasons:
      antiretroviral-related adverse effects; comorbidities; risk of interactions; or
      archived resistance. Patients had >=24 weeks of follow-up. Population,
      virological and immunological responses and safety and tolerability are
      described. RESULTS: Thirty-three (22 on PIs, of whom 18 had ritonavir-boosted PI
      monotherapy) patients were identified: median (IQR) age of 56 (50-62) years, 55%
      women, median (IQR) of 19 (17-23) years of known HIV infection, 39% prior AIDS
      events, median (IQR) of 8 (4-13) years with undetectable plasma HIV-1 RNA and
      median (IQR) CD4 cell count of 596 (420-843) cells/mm(3). Twenty-five (76%)
      patients had antiretroviral-related adverse effects, 32 (97%) patients had
      comorbidities, 28 (85%) patients had risk of interactions and 16 (48%) patients
      had archived resistance. One patient with suboptimal adherence had low-level
      virological failure through weeks 4-24. HIV RNA genotypic resistance tests
      detected no integrase mutations at weeks 4 and 24, but 118R was detected in 7% of
      the integrated HIV DNA at 24 weeks. Patients had significant median decreases in
      triglycerides (-117 mg/dL), total cholesterol (-36 mg/dL), the total
      cholesterol/HDL cholesterol ratio (-0.7) and high-sensitivity C-reactive protein
      (-0.05 mg/dL) (P <= 0.007), although the Chronic Kidney Disease Epidemiology
      Collaboration equation also decreased (-7.1 mL/min) (P < 0.0001). CONCLUSIONS:
      These data suggest the efficacy of dolutegravir monotherapy as a maintenance
      strategy to be further confirmed in randomized clinical trials.

PMID- 27021342
TI  - Fatigue and Its Associated Factors in Spinocerebellar Ataxia Type 3/Machado
      Joseph Disease.
AB  - Fatigue has been described in several neurodegenerative diseases, reducing
      quality of life. A systematic evaluation of this clinical feature is lacking in
      SCA3/MJD. The aim of this study was to evaluate the frequency and the factors
      associated with fatigue in SCA3/MJD. Patients with SCA3/MJD and matched healthy
      controls answered the Modified Fatigue Impact Scale (MFIS), Beck Inventory
      Depression (BDI) and Epworth Sleepiness Scale (ESS). Scale for the assessment and
      rating of ataxia (SARA) was used to determine ataxia severity. We used Mann
      Whitney and Fisher exact tests to compare mean scores and proportions between
      groups. Linear regression analyses were employed to investigate factors
      associated with fatigue in SCA3/MJD. Seventy-four patients were included with a
      mean age and disease duration of 47.2 +/- 12.8 and 9.5 +/- 6.37 years,
      respectively. There were 38 men and 36 women. Mean (CAG)n was 72.2 +/- 3.8. Mean
      MFIS score was higher in patients with SCA3/MJD (41.4 +/- 16.2 vs 18.4 +/- 12.9,
      p < 0.001). According to BDI scores, relevant depressive symptoms were found in
      69.4 % of patients but only in 10.4 % of controls (p < 0.001). The proportion of
      patients with ESS scores indicating excessive daytime somnolence was also higher
      than controls (37.5 vs 22.3 %, p = 0.05). In the multiple regression analysis,
      both BDI and ESS scores were associated with fatigue (r = 0.67, p < 0.001 and p =
      0.01). Fatigue is frequent and strongly associated with depression and excessive
      daytime somnolence in SCA3/MJD.

PMID- 27021344
TI  - Response to the Letter to the Editor-Re: Gastric Band Removal in Revisional
      Bariatric Surgery, One-Step Versus Two-Step: a Systematic Review and Meta
      analysis.

PMID- 27021343
TI  - Remembering Collective Violence: Broadening the Notion of Traumatic Memory in
      Post-Conflict Rehabilitation.
AB  - In the aftermath of war and armed conflict, individuals and communities face the
      challenge of dealing with recollections of violence and atrocity. This article
      aims to contribute to a better understanding of processes of remembering and
      forgetting histories of violence in post-conflict communities and to reflect on
      related implications for trauma rehabilitation in post-conflict settings.
      Starting from the observation that memory operates at the core of PTSD
      symptomatology, we more closely explore how this notion of traumatic memory is
      conceptualized within PTSD-centered research and interventions. Subsequently, we
      aim to broaden this understanding of traumatic memory and post-trauma care by
      connecting to findings from social memory studies and transcultural trauma
      research. Drawing on an analysis of scholarly literature, this analysis develops
      into a perspective on memory that moves beyond a symptomatic framing toward an
      understanding of memory that emphasizes its relational, political, moral, and
      cultural nature. Post-conflict memory is presented as inextricably embedded in
      communal relations, involving ongoing trade-offs between individual and
      collective responses to trauma and a complex negotiation of speech and silence.
      In a concluding discussion, we develop implications of this broadened
      understanding for post-conflict trauma-focused rehabilitation.

PMID- 27021345
TI  - Gastric Band Removal in Revisional Bariatric Surgery: a One-Step or Two-Step
      Procedure?

PMID- 27021346
TI  - Characterization of nitrogen substrate limitation on Escherichia coli's growth by
      parameter identification tools.
AB  - Carbon-to-nitrogen ratio (CNR) has shown to be a relevant factor in
      microorganisms growth and metabolites production. It is usual that this factor
      compromises the productivity yield of different microorganisms. However, CNR has
      been rarely modeled and therefore the nature of its specific influence on
      metabolites production has not been understood clearly. This paper describes a
      parametric characterization of the CNR effect on the Escherichia coli metabolism.
      A set of parameters was proposed to introduce a mathematical model that considers
      the biomass, substrate and several byproducts dynamical behavior under batch
      regimen and CNR influence. Identification algorithm used to calculate the
      parameters considers a novel least mean square strategy that formalizes the CNR
      influence in E. coli metabolism. This scheme produced a step-by-step method that
      was suitable for obtaining the set of parameters that describes the model. This
      method was evaluated under two scenarios: (a) using the data from a set of
      numerical simulations where the model was tested under the presence of artificial
      noises and (b) the information obtained from a set of experiments under different
      CNR. In both cases, a leave-one-experiment-out cross-validation study was
      considered to evaluate the model prediction capabilities. Feasibility of the
      parametric identification method was proven in both considered scenarios. 

PMID- 27021347
TI  - Improving the production yield and productivity of 1,3-dihydroxyacetone from
      glycerol fermentation using Gluconobacter oxydans NL71 in a compressed oxygen
      supply-sealed and stirred tank reactor (COS-SSTR).
AB  - In this study, a compressed oxygen gas supply was connected to a sealed aerated
      stirred tank reactor (COS-SSTR) bio-system, leading to a high-oxygen pressure
      bioreactor used to improve the bio-transformative performance in the production
      of 1,3-dihydroxyacetone (DHA) from glycerol using Gluconobacter oxydans NL71. A
      concentration of 301.2 +/- 8.2 g L(-1) DHA was obtained from glycerol after 32 h
      of fed-batch fermentation in the COS-SSTR system. The volumetric productivity for
      this process was 9.41 +/- 0.23 g L(-1) h(-1), which is presently the highest
      obtained level of glycerol bioconversion into DHA. These results show that the
      application of this bioreactor would enable microbial production of DHA from
      glycerol at the industrial scale. 

PMID- 27021348
TI  - Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian
      children 6-11 years of age: CHMS 2007-2009.
AB  - Childhood developmental disorders and related problems such as learning
      disabilities and attention deficit hyperactivity disorder (ADHD) account for a
      growing burden on the family, education and health care systems. Exposure to
      environmental chemicals such as bisphenol A (BPA) and phthalates may play a role
      in the development of child behavioral problems. Using cross-sectional data from
      Cycle 1 of the Canadian Health Measures Survey (CHMS), we examined the potential
      association between urinary concentrations of BPA and various phthalate
      metabolites and child learning and behavioral problems, considering important
      covariates such as gender, blood lead and environmental tobacco smoke (ETS). The
      Strengths and Difficulties Questionnaire (SDQ) outcomes of interest were
      emotional symptoms, hyperactivity/inattention, and a total difficulties score
      with borderline and abnormal scores grouped together and compared with children
      with normal scores. Other outcomes studied included any reported learning
      disability, a subset of learning disabilities reported as ADD/ADHD (attention
      deficit disorder) and use of psychotropic medications in the past month. Among
      children ages 6-11 years, the prevalences of any learning disability, ADD, and
      ADHD were 8.7%, 1.5% and 2.8%, respectively. Estimated prevalences for SDQ
      hyperactivity/inattention, emotional symptoms and total difficulties scores were
      16.9%, 15.0%, and 13.0%, respectively. Child's urinary BPA was associated with
      taking psychotropic medications (OR 1.59; 95% CI 1.05-2.40). Urinary MBzP
      concentration was significantly associated with emotional symptoms in girls (OR
      1.38 95% CI 1.09-1.75) but not in boys (OR 1.05 95% CI 0.82-1.36).) Blood lead
      was significantly associated with several of the outcomes examined, with a
      significant interaction observed between prenatal smoking and blood lead for the
      total difficulties score (OR=10.57; 95% CI 2.81-39.69 vs. OR=1.98; 95% CI 1.41
      2.79 if mother did not smoke during pregnancy). Although limited by the cross
      sectional nature of the study which precludes examining causation, the results
      suggest that although some indicators of child behavior were significantly
      associated with their urinary BPA and phthalate concentrations, the major
      chemical associated with adverse behavioral indicators was lead.

PMID- 27021349
TI  - Characterization of the Microbial Communities in the Ant Lion Euroleon coreanus
      (Okamoto) (Neuroptera: Myrmeleontidae).
AB  - Euroleon coreanus (Okamoto) is widely distributed in China, and the larval stage
      can be treated as traditional Chinese medicine. However, the host-bacterium
      relationship remains unexplored, as there is a lack of knowledge on the microbial
      community of ant lions. Hence, in the current study, we explored the microbial
      community of the larval ant lion E. coreanus using Illumina MiSeq sequencing.
      Results indicated that a total of 10 phyla, 126 genera, and 145 species were
      characterized from the second instars of E. coreanus, and most of the microbes
      were classified in the phylum Proteobacteria. Cronobacter muytjensii was the most
      abundant species characterized in the whole body and gut of E. coreanus, and the
      unclassified species in the genera Brevundimonas and Lactobacillus were
      relatively more abundant in the head and carcass. In addition, no Wolbachia-like
      bacteria were detected, whereas bacteria like Francisella tularensis subsp.
      Holarctica OSU18 and unclassified Rickettsiella were first identified in ant lion
      E. coreanus. 

PMID- 27021350
TI  - Comparison of silodosin to tamsulosin for medical expulsive treatment of ureteral
      stones: a systematic review and meta-analysis.
AB  - This study aimed at comparing the success rates of silodosin to the most commonly
      used for medical expulsive therapy (MET) tamsulosin for the management of
      ureteral stones. A systematic review using the search string: "silodosin AND
      (ston* OR calcu* OR expul*)" was conducted on Pubmed, SCOPUS, Web of Science,
      Cochrane Central Register. The Primary endpoint was the stone expulsion rate.
      Secondary endpoint was the time to stone expulsion. Two authors independently
      screened the studies depending on inclusion and exclusion criteria. Meta-analysis
      and forest-plot figures were calculated with the software Review Manager (RevMan
      5.3.5). Variations were evaluated with the chi 2 statistical method and
      heterogeneity with I 2 index. After screening of 39 publications obtained by the
      initial search, three randomized controlled trials were eligible to be included
      in the meta-analysis. 407 patients were pooled. Favorable results were observed
      for silodosin in terms of stone expulsion rates with a risk ratio of 1.33 (95 %
      CI 1.17-1.50) (I 2 = 0 %). Similarly, faster stone expulsion times were observed
      with silodosin when compared with tamsulosin. Mean difference -2.49 (95 % CI 
      3.40 to 1.58) (I 2 = 89 %). This meta-analysis showed significantly higher stone
      expulsion rates and faster expulsion times in favor of silodosin when compared to
      tamsulosin.

PMID- 27021351
TI  - About the numerical robustness of biomedical benchmark cases: Interlaboratory
      FDA's idealized medical device.
AB  - The need for reliable approaches in numerical simulations stands out as a
      critical issue for the development and optimization of cardiovascular biomedical
      devices. This led the US Food and Drug Administration to undertake a programme of
      validation of computational fluid dynamics methods for transitional and turbulent
      flows. In the current investigation, large-eddy simulation is used to simulate
      the flow in the first benchmark medical device, and results are confronted to the
      existing laboratory experiments. This idealized medical device has the
      particularity to feature transition to turbulence after a sudden expansion. The
      effects of numerical parameters and low-level inlet perturbations are
      investigated. Results indicate a considerable impact of numerical aspects on the
      prediction of the location of the transition to turbulence. The study also
      demonstrates that injecting small perturbations at the inflow greatly improves
      the streamwise velocity estimation in the transition region and substantially
      contributes to the robustness of the flow statistical data. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27021352
TI  - Vasoactive intestinal peptide promotes differentiation and clock gene expression
      in granulosa cells from prehierarchal follicles.
AB  - Vasoactive intestinal peptide (VIP) signaling via cyclic adenosine monophosphate
      (cAMP) is reported to stimulate steroidogenesis in ovarian granulosa cells from a
      variety of vertebrate species, including the domestic hen. Prior to follicle
      selection in the hen ovary (i.e., cyclic recruitment) follicle-stimulating
      hormone (FSH)-induced cAMP signaling is absent within the granulosa layer until
      immediately following follicle selection. As a consequence, granulosa cells
      remain in an undifferentiated state and are unable to initiate FSH-induced
      steroidogenesis. VIP receptors (VPAC1 and VPAC2), like the FSH receptor, are G
      protein-coupled receptors, so we predicted that VIP signaling in granulosa cells
      is also absent in follicles that have not yet been selected into the preovulatory
      hierarchy. Initial studies established that mRNA encoding VPAC1 and VPAC2 are
      expressed within the granulosa cells throughout follicle development.
      Nevertheless, undifferentiated granulosa cells from prehierarchal (6-8 mm)
      follicles do not accumulate cAMP in response to a 4-hr incubation with chicken
      VIP; the capacity for such receptor signaling is attained only following
      selection within actively differentiating granulosa cells. VIP treatment did,
      however, increase expression of mRNA encoding the Gallus circadian clock protein,
      BMAL1-but only in granulosa cells collected from selected follicles. These
      findings provide evidence that, at follicle selection, the acquisition of VIP
      induced cAMP cell signaling helps initiate and promote the differentiation of of
      granulosa cells. Furthermore, we propose that VIP signaling may regulate BMAL1
      expression and, thus, a daily rhythmicity within granulosa cells of preovulatory
      follicles. Mol. Reprod. Dev. 83: 455-463, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27021353
TI  - Phase-contrast MRI volume flow--a comparison of breath held and navigator based
      acquisitions.
AB  - BACKGROUND: Magnetic Resonance Imaging (MRI) 2D phase-contrast flow measurement
      has been regarded as the gold standard in blood flow measurements and can be
      performed with free breathing or breath held techniques. We hypothesized that the
      accuracy of flow measurements obtained with segmented phase-contrast during
      breath holding, and in particular higher number of k-space segments, would be non
      inferior compared to navigator phase-contrast. Volumes obtained from anatomic
      segmentation of cine MRI and Doppler echocardiography were used for additional
      reference. METHODS: Forty patients, five women and 35 men, mean age 65 years
      (range 53-80), were randomly selected and consented to the study. All underwent
      EKG-gated cardiac MRI including breath hold cine, navigator based free-breathing
      phase-contrast MRI and breath hold phase-contrast MRI using k-space segmentation
      factors 3 and 5, as well as transthoracic echocardiography within 2 days.
      RESULTS: In navigator based free-breathing phase-contrast flow, mean stroke
      volume and cardiac output were 79.7 +/- 17.1 ml and 5071 +/- 1192 ml/min,
      respectively. The duration of the acquisition was 50 +/- 6 s. With k-space
      segmentation factor 3, the corresponding values were 77.7 ml +/- 17.5 ml and 4979
      +/- 1211 ml/min (p = 0.15 vs navigator). The duration of the breath hold was 17
      +/- 2 s. K-space segmentation factor 5 gave mean stroke volume 77.9 +/- 16.4 ml,
      cardiac output 5142 +/- 1197 ml/min (p = 0.33 vs navigator), and breath hold time
      11 +/- 1 s. Anatomical segmentation of cine gave mean stroke volume and cardiac
      output 91.2 +/- 20.8 ml and 5963 +/- 1452 ml/min, respectively. Echocardiography
      was reliable in 20 of the 40 patients. The mean diameter of the left ventricular
      outflow tract was 20.7 +/- 1.5 mm, stroke volume 78.3 ml +/- 15.2 ml and cardiac
      output 5164 +/- 1249 ml/min. CONCLUSIONS: In forty consecutive patients with
      coronary heart disease, breath holding and segmented k-space sampling techniques
      for phase-contrast flow produced stroke volumes and cardiac outputs similar to
      those obtained with free-breathing navigator based phase-contrast MRI, using less
      time. The values obtained agreed fairly well with Doppler echocardiography while
      there was a larger difference when compared with anatomical volume determinations
      using SSFP (steady state free precession) cine MRI.

PMID- 27021354
TI  - Impact of Diastolic Function Parameters on the Risk for Left Atrial Appendage
      Thrombus in Patients with Nonvalvular Atrial Fibrillation: A Prospective Study.
AB  - BACKGROUND: In patients with nonvalvular atrial fibrillation (NVAF), the impact
      of left ventricular diastolic function on the risk for left atrial appendage
      (LAA) thrombus has not been prospectively studied. METHODS: At two academic
      medical centers, patients with NVAF were prospectively enrolled to undergo
      investigational transthoracic echocardiography immediately before clinically
      indicated transesophageal echocardiography. Mitral inflow E velocity and tissue
      Doppler septal and lateral mitral annulus velocities (e') were measured, and E/e'
      ratios were calculated. RESULTS: Among 266 subjects (mean age, 65 years; 32%
      women), 17 (6.4%) had LAA thrombus. Patients with LAA thrombus had a higher mean
      CHA2DS2-VASc score (4.6 +/- 1.7 vs 3.0 +/- 1.8, P < .001), a higher mean lateral
      E/e' ratio (19.4 +/- 10.1 vs 10.2 +/- 5.6, P < .001), and a lower mean lateral e'
      velocity (7.0 +/- 3.2 vs 10.4 +/- 3.7 cm/sec, P = .001). There was a good
      discriminative capacity for E/e' (area under the curve, 0.83; P < .001) and e'
      velocity (area under the curve, 0.76; P = .001). None of the patients with normal
      E/e' ratios or normal e' velocities had LAA thrombus. Both E/e' (odds ratio, 1.13
      per point; 95% CI, 1.06-1.20; P < .001) and e' velocity (odds ratio, 0.76 per 1
      cm/sec; 95% CI, 0.63-0.92; P = .005) provided independent and incremental
      predictive value beyond the CHA2DS2-VASc score; however, E/e' provided greater
      incremental value than e' velocity (P = .036). Analyses using septal and averaged
      E/e' and septal e' velocity yielded similar results. Diastolic function
      parameters were also associated with the presence and intensity of left atrial
      spontaneous echo contrast, a precursor of LAA thrombus. CONCLUSIONS: This
      prospective and concomitant evaluation of diastolic function and LAA thrombus in
      patients with NVAF demonstrates that E/e' ratio and e' velocity are associated
      with LAA thrombus, independent of CHA2DS2-VASc score, and may play a role in
      identifying patients at low risk for LAA thrombus. These data suggest that
      diastolic function assessment may improve stroke prediction in patients with
      NVAF.

PMID- 27021355
TI  - Echocardiographic and Fluoroscopic Fusion Imaging for Procedural Guidance: An
      Overview and Early Clinical Experience.
AB  - There has been significant growth in the volume and complexity of percutaneous
      structural heart procedures in the past decade. Increasing procedural complexity
      and accompanying reliance on multimodality imaging have fueled the development of
      fusion imaging to facilitate procedural guidance. The first clinically available
      system capable of echocardiographic and fluoroscopic fusion for real-time
      guidance of structural heart procedures was approved by the US Food and Drug
      Administration in 2012. Echocardiographic-fluoroscopic fusion imaging combines
      the precise catheter and device visualization of fluoroscopy with the soft tissue
      anatomy and color flow Doppler information afforded by echocardiography in a
      single image. This allows the interventionalist to perform precise catheter
      manipulations under fluoroscopy guidance while visualizing critical tissue
      anatomy provided by echocardiography. However, there are few data available
      addressing this technology's strengths and limitations in routine clinical
      practice. The authors provide a critical review of currently available
      echocardiographic-fluoroscopic fusion imaging for guidance of structural heart
      interventions to highlight its strengths, limitations, and potential clinical
      applications and to guide further research into value of this emerging
      technology.

PMID- 27021356
TI  - Concentration and ratio of essential fatty acids influences the inflammatory
      response in lipopolysaccharide challenged mice.
AB  - The goal of this study was to evaluate the role of both the % of dietary, 18
      carbon PUFA (2.5%, 5% and 10%) and the n-6:n-3 ratio (1:1, 10:1 and 20:1) on the
      acute inflammatory response. Mice were fed diets for 8 weeks and injected
      intraperitoneally with LPS to induce acute inflammation. After 24h mice were
      sacrificed and plasma cytokines measured. Diets significantly affected the
      erythrocyte PUFA composition and the effect of PUFA ratio was more prominent than
      of PUFA concentration. The % dietary PUFA affected feed efficiency (p<0.05) and
      there was a PUFA*ratio interaction with body fat (p<0.01). In mice fed high %kcal
      from PUFA, those given a low n-6:n-3 ratio had more body fat than those fed a
      high ratio. Of the twelve cytokines measured, eleven were significantly affected
      by the % PUFA (p<0.05), whereas five were affected by the ratio (p<0.05). For
      seven cytokines, there was a significant PUFA*ratio interaction according to a
      two way ANOVA (p<0.05). These data indicate that dietary polyunsaturated fatty
      acids can affect LPS induced-inflammation.

PMID- 27021357
TI  - The 'Big Five'. Hypothesis generation: a multidisciplinary intervention package
      reduces disease-specific hospitalisations from long-term care: a post hoc
      analysis of the ARCHUS cluster-randomised controlled trial.
AB  - INTRODUCTION: long-term care (LTC) residents have higher hospitalisation rates
      than non-LTC residents. Rapid decline may follow hospitalisations, hence the
      importance of preventing unnecessary hospitalisations. Literature describes
      diagnosis-specific interventions (for cardiac failure, ischaemic heart disease,
      chronic obstructive pulmonary disease, stroke, pneumonia-termed 'big five'
      diagnoses), impacting on hospitalisations of older community-dwellers, but few
      RCTs show reductions in acute admissions from LTC. METHODS: LTC facilities with
      higher than expected hospitalisations were recruited for a cluster-randomised
      controlled trial (RCT) of facility-based complex, non-disease-specific, 9-month
      intervention comprising gerontology nurse specialist (GNS)-led staff education,
      facility benchmarking, GNS resident review and multidisciplinary discussion of
      residents selected using standard criteria. In this post hoc exploratory
      analysis, the outcome was acute hospitalisations for 'big five' diagnoses. Re
      randomisation analyses were used for end points during months 1-14. For end
      points during months 4-14, proportional hazards models are adjusted for within
      facility clustering. RESULTS: we recruited 36 facilities with 1,998 residents
      (1,408 female; mean age 82.9 years); 1,924 were alive at 3 months. The
      intervention did not impact overall rates of acute hospitalisations or mortality
      (previously published), but resulted in fewer 'big five' admissions (RR = 0.73,
      95% CI = 0.54-0.99; P = 0.043) with no significant difference in the rate of
      other acute admissions. When considering events occurring after 3 months (only),
      the intervention group were 34.7% (HR = 0.65; 95% CI = 0.49-0.88; P = 0.005) less
      likely to have a 'big five' acute admission than controls, with no differences in
      likelihood of acute admissions for other diagnoses (P = 0.96). CONCLUSIONS: this
      generic intervention may reduce admissions for common conditions which the
      literature shows are impacted by disease-specific admission reduction strategies.

PMID- 27021358
TI  - Qigong in Injured Military Service Members.
AB  - BACKGROUND: Wounded, ill, and injured (WII) Military Service members experience
      significant stress and are at risk for developing chronic conditions including
      posttraumatic stress disorder and depression. Qigong, a meditative movement
      practice, may positively affect their ability to engage in successful
      rehabilitation. PURPOSE: We assessed the feasibility of Qigong practice in WII
      Service members returning from combat; effects on stress, sleep, and somatic
      symptoms; satisfaction; and participants' experience with the practice. DESIGN:
      Single-group, pre- and posttest, mixed methods approach. METHOD: Twenty-six WII
      were enrolled. The program was designed to include 20 classes over 10 weeks.
      Participants completed self-report questionnaires, practice logs, and an exit
      interview. FINDINGS: Average attendance was 8.14 classes ( SD = 4.9); mean
      engagement was 5.7 ( SD = 3.5) weeks. Participants endorsed a high level of
      satisfaction with the practice. Qualitative themes included coping with stress;
      feeling more resilient and empowered; improvement in symptoms including sleep and
      physical function; and factors affecting practice. Participant-reported
      facilitators included accessibility and portability of the practice; barriers
      included scheduling conflicts and personal challenges. Participants recommended
      offering shorter programs with flexible scheduling options, increasing program
      awareness, and including significant others in future classes. CONCLUSION: Qigong
      was safe, portable, and easily adapted for WII Service members.

PMID- 27021359
TI  - Distribution of calcium-binding proteins, parvalbumin and calbindin, in the
      midbrain auditory center (MLd) of a pigeon.
AB  - Immunohistochemical distribution of calcium-binding proteins, parvalbumin (PV)
      and calbindin (CB), has been studied in the mesencephalic auditory center (MLd)
      of pigeon (Columba livia). In the central region of the MLd (core, ICC), an
      overlap in distribution of the PVand CB-immunopositive (ip) neurons and neuropil
      has been observed, with different patterns in the central and peripheral parts.
      In the peripheral region of the MLd (belt, ICS, and ICX), both neurons and
      neuropil contained only CB. A selective CB chemospecificity of the belt, ICS, and
      ICX is an evolutionary conserved feature characteristic of all avian species.
      Interspecies differences in the distribution of PV and CB immunoreactivity in the
      ICC are a result of adaptive functional specialization, which provides specific
      processing of different aspects of the auditory information. 

PMID- 27021360
TI  - The role of alpha-synuclein in the development of the dopaminergic neurons in the
      substantia nigra and ventral tegmental area.
AB  - Alpha-synuclein is a presynaptic protein of vertebrates that belongs to the
      family of synucleins. Normal functions of synucleins remain unknown. Alpha
      synuclein is one of the causative factors of the familial and idiopathic forms of
      Parkinson's disease (PD). The progressive loss of dopaminergic (DA) neurons is
      characteristic of PD and the most severe damage occurs in the substantia nigra
      (SN). This leads to an erraticism of the synthesis and synaptic secretion of the
      neurotransmitters, subsequently resulting in the loss of the connections between
      brain areas. This work shows that alpha-synuclein is directly involved in the
      formation of the mature DA neurons of the midbrain at different stages of the
      ontogenesis and these findings are consistent with data obtained in other
      studies. Thus, alpha-synuclein may have a varying modulating effect on the growth
      dynamics and the fate of populations of DA neurons. 

PMID- 27021361
TI  - Parasitizing of trematodes provokes warts on the hinge plate of the bivalve
      mollusk Macoma balthica Linnaeus, 1758 (Veneroida, Tellinidae).
AB  - The hypothesis on non-random correlation between abnormalities in the structure
      of hinge plate and infection of mollusks Macoma balthica with trematodes of the
      family Gymnophallidae has been tested on the basis of material from the Barents
      Sea. Significant correlation between the presence of warts and infection was
      established upon intraand interpopulation comparison. The hypothesis states that
      parasitizing of trematodes in the extrapallial cavity of mollusks influences the
      mantle functioning and provokes abnormalities in the hinge plate structure. 

PMID- 27021362
TI  - The first record of calcareous dinoflagellate cysts from the Upper Cretaceous of
      the Volga River Region.
AB  - The taxonomic position of the microproblematics previously considered to be
      Foraminifera or Calcisphaerulidae is established. The first record from Russia of
      calcareous cysts of Dinoflagellata is presented. The microfossils originate from
      the Maastrichtian siliceous clay of the Volga River Region. 

PMID- 27021363
TI  - Fine structure of agglutinated tubes of polychaetes of the family Terebellidae
      (Annelida).
AB  - The results of the first study on the fine structure of agglutinated tubes of the
      family Terebellidae are presented. 

PMID- 27021364
TI  - Tactile reception in the outer head cover of goldfish (Carassius auratus
      gibelio).
AB  - The first data on the responses of tactile receptors of the tonic, phasic, and
      mixed types to mechanic stimulation of the surface of head skin of fish obtained
      by means of noninvasive recording of potentials are presented. The sensitivity of
      skin tactile receptors is the highest in the circumoral and gular zones, which
      reflects their functional role in foraging behavior. 

PMID- 27021365
TI  - Kinematic constituents of the extreme head turn of Strix aluco estimated by means
      of CT-scanning.
AB  - To analyze extreme sideways turn of the head in owls, a total fresh specimen of
      Strix aluco was frozen in respective posture and CT-scanned. The maximum turn to
      one side was found to be 360 degrees , provided that the head is drawn into the
      shoulders. 160 degrees  of this full turn are ensured by the neck axial rotation
      (this includes ~90 degrees  twist of the head relative to epistropheus and,
      posterior to it, less than 15 degrees  per every cervical joint), and the rest
      200 degrees  are ensured by combination of dorsal and lateral flexion. The 15
      degrees  limit is overcome in five joints in respect of dorsiflexion, and in six
      joints in respect of lateral flexion. So large a degree of lateral mobility is
      unusual among birds, and is appreciated as a crucial adaptation to extreme head
      turning. 

PMID- 27021366
TI  - Productivity and biomass of trematode (Digenea) parasites in lake ecosystems.
AB  - The first estimation of the annual production and biomass of cercariae (free
      swimming transmission stage of digenetic trematodes) in a lake ecosystem has been
      performed. The biomass of cercariae is comparable with that of free-living
      invertebrates and may make a significant contribution to the energy flow in lake
      ecosystems. 

PMID- 27021367
TI  - On the growth and regeneration of the exoskeleton in early jawless vertebrates
      (Osteostraci, Agnatha).
AB  - Based on the study of sculpture of the cephalic shield and histological structure
      of the exoskeleton in Reticulaspis menneri Afanassieva et Karatajute -Talimaa
      (Osteostraci, Agnatha) from the Lower Devonian of the Severnaya Zemlya
      Archipelago, it has been established that, in the ontogeny of the form under
      study, dentin generation of the exoskeleton may have developed repeatedly,
      depending on the requirements of the organism. It is established for the first
      time that, on the shield surface of osteostracans, dentin structures of various
      types (tubercles, ridges, networks) could be formed both primarily and in
      subsequent generations with the growth of the exoskeleton. Injury of the
      integument and, hence, changes in mechanical tension in covering tissues caused
      activation of the formation of subsequent generations (of dentin) in the areas
      involved in reparative regeneration of the shield. 

PMID- 27021368
TI  - A decrease in heat insulation of the black-clawed brush-furred rat (Lophuromys
      melanonyx, Petter) during adaptation to high altitudes.
AB  - The results of the body-surface infrared thermography of rodents of the genus
      Lophuromys suggest that heat insulation of the black-clawed brush-furred rat L.
      melanonyx, a large specialized species of the AfroAlpine zone, is worse than that
      of the related smaller species, the golden-footed (L. chrysopus) and shorttailed
      (L. brevicaudus) brush-furred rats, that inhabit tropical forest and Erica shrub,
      respectively. A decrease in heat insulation of the alpine species may facilitate
      the use of solar radiation for supporting heat balance of these diurnal animals. 

PMID- 27021369
TI  - Role of the tissue free amino acids in adaptation of medicinal leeches Hirudo
      medicinalis L., 1758 to extreme climatic conditions.
AB  - The first comparison of the spectra of free amino acids in tissues of the
      medicinal leeches H. medicinalis from different climatic and geographical
      Eurasian areas has been performed. Adaptation of H. medicinalis to extreme
      climatic conditions occurs via intensification of the amino acid metabolism
      resulting from a significant increase in the content of essential amino acids.
      Accumulation of arginine, histidine, and lysine (3.6-, 3.9-, and 2.0-fold
      increases, respectively) has proved to play a special protective role in
      adaptation of H. medicinalis to the low positive temperatures. 

PMID- 27021370
TI  - Effect of polyclonal activators on cytokine production by blood cells and by
      malignant breast cancer cells.
AB  - The production of cytokines by peripheral blood cells and biopsy specimens of
      tumors stimulated by polyclonal activators (PAs) was evaluated in 34 patients
      with invasive ductal breast carcinoma using enzyme-linked immunosorbent assay
      (ELISA). Positive correlation between the stimulation index of polyclonal
      activators (SIPA) for IL-18 production by the tumor and the relative content of
      poorly differentiated cells was revealed. The latter, in turn, was positively
      correlated with the numbers of normal and pathologic mitoses and the degree of
      malignancy. Cancer cells can produce IL-18, which is involved in the process of
      angiogenesis, stimulates invasion and metastasis. Decrease in SIPA for the
      production of IL-6 and GCSF by peripheral blood cells could serve as an indicator
      of malignant progression in invasive ductal breast carcinoma. 

PMID- 27021372
TI  - Hyperosmolarity normalises serum-induced changes to chondrocyte properties in a
      model of cartilage injury.
AB  - Partial-thickness cartilage injuries do not heal effectively, potentially leading
      to degeneration as occurs in post-traumatic osteoarthritis (PTOA). The role of
      chondrocytes could be crucial in determining the nature of the repair; however,
      their response to this injury is poorly understood. We have utilised an in vitro
      bovine osteochondral partial-thickness scalpel injury model and determined
      chondrocyte properties at and distant from the injury in the presence/absence of
      (a) serum-free DMEM (340 mOsm), (b) synovial fluid DMEM (SF-DMEM), (c) foetal
      calf serum DMEM (FCS-DMEM), (d) hyperosmolar serum-free DMEM (600 mOsm), or (e)
      hyperosmolar FCS-DMEM for up to two weeks. Chondrocytes were fluorescently
      labelled with 5-chloromethylfluorescein-diacetate (CMFDA)/propidium iodide (PI)
      for live/dead cells and imaged using confocal microscopy. Quantitative data were
      obtained on chondrocyte properties (cell volume, clusters, morphology) at and
      distant from the injury. In serum-free DMEM, chondrocyte morphology at the injury
      remained unaffected throughout culture. However, with SF-DMEM or FCS-DMEM the
      chondrocytes displayed an increase in volume (p < 0.0001), cluster formation
      (FCS; p < 0.01) and abnormal morphology (p < 0.001) compared to serum-free DMEM.
      Cluster formation and shape changes during FCS-DMEM culture were more pronounced
      than with SF-DMEM. SF-DMEM or FCS-DMEM stimulated these changes to chondrocytes
      at the injury with only small effects on distant cells. Hyperosmolarity inhibited
      the morphological and volume changes to chondrocytes induced by FCS-DMEM (p <
      0.001) and the injured cartilage had the appearance of that in serum-free DMEM.
      Raised osmolarity may therefore have benefit in preserving the morphological
      phenotype of chondrocytes at the site of injury, and thus promote more effective
      integrative repair in partial-thickness cartilage injury.

PMID- 27021371
TI  - Apoptotic tumor cell death under the influence of the cytotoxic complex Tag7
      Hsp70 is induced by interaction with the TNFR1 receptor.
AB  - The results of comparative analysis of interaction between the protein cytotoxic
      complex Tag 7-Hsp70 and the Tag 7 component of this complex with TNFR1 receptor
      in solution and in tumor cells are presented. 

PMID- 27021373
TI  - Growing healthy children and communities: Children's insights in Lao People's
      Democratic Republic.
AB  - A diverse group of 103 children aged 7-11 years old living in family and
      residential care in rural and urban settings in two northern provinces in Lao
      People's Democratic Republic participated in group discussions using images and
      community mapping. Children's identified sources of risk and protection
      illustrate primary public health and protection concerns and resources. Young
      children worried about lack of hygiene, unintentional injuries, corporal
      punishment, and domestic violence. They also expressed concern about gambling and
      children sleeping in the streets, even if they had never seen any of the latter
      in their communities. In contrast, food and shelter; artistic, religious, and
      cultural practices; supportive interpersonal relationships; and schooling largely
      evoked feelings of safety and belonging. Images that prompted conflicting
      interpretations surfaced individual and contextual considerations that nuanced
      analysis. Researchers and decision-makers will benefit from using this
      developmentally appropriate, context-sensitive child-centred visual method to
      elicit young children's views of risk and protection. It may also serve as a tool
      for public health education. Involving young children in the initial selection of
      images would further enhance the efficiency of the method.

PMID- 27021374
TI  - Product limit estimation for capturing of pressure distribution dynamics.
AB  - Measurement of contact pressures at the wheelchair-seating interface is a
      critically important approach for laboratory research and clinical application in
      monitoring risk for pressure ulceration. As yet, measures obtained from pressure
      mapping are static in nature: there is no accounting for changes in pressure
      distribution over time, despite the well-known interaction between time and
      pressure in risk estimation. Here, we introduce the first dynamic analysis for
      distribution of pressure data, based on the Kaplan-Meier (KM) Product Limit
      Estimator (PLE) a ubiquitous tool encountered in clinical trials and survival
      analysis. In this approach, the pressure array-over-time data set is sub-sampled
      two frames at a time (random pairing), and their similarity of pressure
      distribution is quantified via a correlation coefficient. A large number (here:
      100) of these frame pairs is then sorted into descending order of correlation
      value, and visualized as a KM curve; we build confidence limits via a bootstrap
      computed over 1000 replications. PLEs and the KM have robust statistical support
      and extensive development: the opportunities for extended application are
      substantial. We propose that the KM-PLE in particular, and dynamic analysis in
      general, may provide key leverage on future development of seating technology,
      and valuable new insight into extant datasets. 

PMID- 27021375
TI  - Multifractal anisotropic swimming: the optimal foraging behaviour of grouper
      larvae.
AB  - It was hypothesized that the Malabar grouper Ephinephelus malabaricus larvae have
      developed search patterns adapted to the distribution of their prey to maximise
      their net energy intake per unit time. Analysis of the swimming behaviour of E.
      malabaricus larvae in both the presence and absence of Artemia sp. nauplii is
      presented to test this hypothesis. A method derived from turbulence studies (the
      moment function of the displacements) was used to characterize the behaviour. The
      results revealed that larval swimming pattern was multifractal (intermittent and
      long-range-correlated) and isotropic (i.e. uniform in all directions) in the
      presence of prey, but multifractal and anisotropic (i.e. more frequent long
      displacement on the vertical axis) in the absence of prey. It is suggested that
      the search behaviour observed in the absence of prey is an adaptive response to
      prey distribution pattern, which is often characterised by multifractality and
      anisotropy (i.e. larger patches on the horizontal axes). In the presence of prey,
      E. malabaricus shifted to intensive search behaviour. Other possible contributors
      to the observed patterns are discussed. It is concluded that multifractality and
      anisotropy of swimming patterns observed in the experiment are mainly explained
      in an optimal foraging theory framework. 

PMID- 27021376
TI  - Arterial cutdown reduces complications after brachial access for peripheral
      vascular intervention.
AB  - OBJECTIVE: Factors influencing risk for brachial access site complications after
      peripheral vascular intervention are poorly understood. We queried the Society
      for Vascular Surgery Vascular Quality Initiative to identify unique demographic
      and technical risks for such complications. METHODS: The Vascular Quality
      Initiative peripheral vascular intervention data files from years 2010 to 2014
      were analyzed to compare puncture site complication rates and associations
      encountered with either brachial or femoral arterial access for peripheral
      vascular intervention. Procedures requiring multiple access sites were excluded.
      Complications were defined as wound hematoma or access vessel stenosis/occlusion.
      Univariate and hierarchical logistic regression was used to identify independent
      factors associated with site complications after brachial access. RESULTS: Of
      44,634 eligible peripheral vascular intervention procedures, 732 (1.6%) were
      performed through brachial access. Brachial access was associated with an
      increased complication rate compared with femoral access (9.0% vs 3.3%; P <
      .001), including more hematomas (7.2% vs 3.0%; P < .001) and access site
      stenosis/occlusion (2.1% vs 0.4%; P < .001). On univariate analysis, factors
      associated with brachial access complications included age, female gender, and
      sheath size. Complications occurred less frequently after arterial cutdown (4.1%)
      compared with either ultrasound-guided (11.8%) or fluoroscopically guided
      percutaneous access (7.3%; P = .07 across all variables). Neither surgeons'
      overall peripheral vascular intervention experience nor prior experience with
      brachial access predicted likelihood of adverse events. By multivariate analysis,
      male gender (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.28-0.84; P <
      .01) and arterial cutdown (OR, 0.25; 95% CI, 0.07-0.87; P = .04) were associated
      with significantly decreased risk for access complications. Larger sheath sizes
      (>5F) were associated with increased risk of complications (OR, 2.19; 95% CI,
      1.07-4.49; P = .03). CONCLUSIONS: Brachial access for peripheral vascular
      intervention carries significantly increased risks for access site occlusion or
      hematoma formation. Arterial cutdown and smaller sheath diameters are associated
      with lower complication rates and thus should be considered when arm access is
      required.

PMID- 27021377
TI  - Results of a randomized clinical trial of external beam radiation to prevent
      restenosis after superficial femoral artery stenting.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of
      external beam radiation (EBR) in preventing restenosis after superficial femoral
      artery (SFA) stenting in comparison with a control group treated with SFA
      stenting only. METHODS: In this Institutional Review Board-approved study,
      patients who provided written informed consent were randomly assigned to 0 Gy or
      14 Gy of EBR to the stent site 24 hours after SFA stenting. The primary end point
      was the angiographic binary restenosis rate 2 years after stenting. Categorical
      and continuous end points were respectively analyzed using logistic regression
      models and Wilcoxon tests. End points expressed as time to event were analyzed
      using a log-rank test. RESULTS: The study included 155 patients, 46 women and 109
      men (mean age, 66 years; range, 45-85 years). In the 0 and 14 Gy groups, binary
      restenosis was present, respectively, in 44% (34/77) and 68% (52/76; P = .003) 2
      years after stenting. Stent thrombosis occurred in 13% (10/78) of the 0 Gy group
      and in 33% (25/77) of the 14 Gy group (P = .003). Target lesion revascularization
      at 2 years was 26% (25/78) in the 0 Gy group and 30% (23/77) in the 14 Gy group
      (P = .56). There were no significant differences in total walking distances
      change from baseline to 2 years (46 +/- 100 and 26 +/- 79 m, respectively, in the
      0 Gy and 14 Gy group; P = .25). There were no procedure-related deaths and no
      major amputations. CONCLUSIONS: A single 14 Gy dose of EBR to the SFA stenting
      site did not prevent in-stent restenosis.

PMID- 27021378
TI  - Carotid artery disease progression and related neurologic events after carotid
      endarterectomy.
AB  - OBJECTIVE: During the last decade, there has been a dramatic improvement in best
      medical treatment for patients with vascular disease. Yet, there is a paucity of
      contemporary long-term data for restenosis and contralateral internal carotid
      artery (ICA) progression. This study assessed ipsilateral and contralateral
      disease progression and cerebrovascular events after carotid endarterectomy
      (CEA). METHODS: A consecutive cohort of CEAs between January 1, 2000, and
      December 31, 2010, was retrospectively analyzed. End points were restenosis >=50%
      and >=70%, contralateral carotid disease progression (50%-69%, 70%-99%, or
      occlusion) and stroke. Survival analysis and Cox regression models were used to
      assess the effect of baseline predictors. RESULTS: During the 11-year study
      period, 1639 patients underwent 1782 CEAs (50.0% patch closure, 23.9% primary
      closure, 26.1% eversion, and 2.5% combined with coronary artery bypass grafting).
      The combined stroke/death rate was 2.6% overall and 1.8% in the asymptomatic
      cohort. The rate of restenosis >=50% at 2, 5, and 10 years was 8.5%, 15.6%,
      27.2%, and the rate for restenosis >=70% was 3.4%, 6.5%, 10.2%, respectively.
      Restenosis >=50% was predicted by hypertension (hazard ratio [HR], 2.09; P =
      .027), female gender (HR, 1.43; P = .042), and younger age (<=65 years; HR, 1.56;
      P = .016), but not by statins, surgical technique, symptoms, or other baseline
      risk factors. Restenoses remained asymptomatic in 125 of 148 (84.5%). Progression
      of contralateral ICA disease at 2, 5, and 10 years was estimated at 5.4%, 15.5%,
      and 46.8%, respectively. Contralateral progression was only predicted by smoking
      (HR, 1.74; P = .008). The stroke rate in patients with disease progression of the
      contralateral ICA was not different compared with those without progression (7.0%
      vs 3.3%; P = .063). Any-stroke rates at 2, 5, and 10 years were 4.6%, 7.3%, and
      15.7%, respectively. Predictors were symptomatic lesion (HR, 1.48; P = .039),
      renal insufficiency, defined as a glomerular filtration rate (GFR) of 30 to 59 vs
      <30 mL/min/1.73 m2 (HR, 0.34; P = .009) or GFR >=60 vs GFR <30 mL/min/1.73 m2
      (HR, 0.55; P = .109), and statin use (HR, 0.59; P = .006). CONCLUSIONS:
      Restenosis or contralateral disease progression after CEA, to a level that might
      warrant consideration for treatment, is very low. The potentially associated
      stroke rates are also very low and not clearly related to disease progression.
      With the exception of the postoperative duplex, surveillance within short
      intervals of <1 or 2 years cannot be justified.

PMID- 27021379
TI  - Autologous bone marrow mononuclear cell therapy for critical limb ischemia is
      effective and durable.
AB  - OBJECTIVE: We have previously shown that autologous bone marrow mononuclear cell
      (ABMNC) therapy improves measures of limb perfusion, rest pain, wound healing,
      and amputation-free survival (AFS) at 1 year in patients with critical limb
      ischemia (CLI). Long-term durability of ABMNC therapy for CLI remains unknown.
      The objective of the current study was to evaluate long-term clinical outcomes 5
      years after treatment. METHODS: Data were retrospectively gathered from a
      database and via a patient survey and review of medical records of patients
      previously enrolled in this phase I/II trial. AFS, freedom from major amputation,
      and freedom from major adverse limb events (MALE) were calculated using the
      product-limit estimate. The incidence of cardiac, malignant, and other medical
      events relevant to the safety of cell therapy were tabulated during the time from
      treatment to follow-up. RESULTS: Twenty-one of the 24 patients (88%) who
      completed the initial 1-year phase I/II trial were available for the 5-year
      analysis; AFS was 74% (95% confidence interval [CI], 0.53-0.87), freedom from
      major amputation was 78% (95% CI, 0.58-0.90), and freedom from MALE was 65% (95%
      CI, 0.45-0.80). Three patients (14%) had major cardiac events. There were no
      incidences of malignancies or diagnoses of clinically significant proliferative
      retinopathy. Fifteen patients (71%) report continued improvement in pain-free
      walking. Nineteen (90%) patients believed that the study was of significant
      medical value and would participate again. CONCLUSIONS: ABMNC therapy provides
      long-term freedom from AFS, major amputation, and MALE that are comparable with
      other reports of patients who underwent surgical and endovascular interventions
      for CLI. Furthermore, no patients developed tumorigenesis or clinically
      significant retinopathy. Because of the limited number of patients studied, our
      findings will need to be followed up in a larger phase III trial.

PMID- 27021380
TI  - 64-Year-Old-Woman With Chest Pressure and Shortness of Breath.

PMID- 27021381
TI  - Characterization and primary functional analysis of a bamboo NAC gene targeted by
      miR164b.
AB  - KEY MESSAGE: PeSNAC1 , a stress-related NAC1 from Phyllostachys edulis , was
      characterized. Ectopic expression in Arabidopsis indicated that PeSNAC1 together
      with ped -miR164b participated in the regulation of organ boundaries and stress
      tolerance. NAC (NAM, ATAF1/2 and CUC2) participates in many different processes
      regulating plant growth, development, and stress response. A total of 125 NAC
      genes have been predicted in moso bamboo (Phyllostachys edulis), but their roles
      are poorly understood. PeSNAC1 targeted by ped-miR164b was focused for further
      study. The cleavage of PeSNAC1 mRNA guided by ped-miR164b was validated using RLM
      5' RACE. Tissue-specific expression analysis demonstrated that ped-miR164b had a
      declining trend from root, sheath, leaf, to that of stem, which was opposite to
      that of PeSNAC1. Transgenic Arabidopsis plants overexpressing either PeSNAC1 (OX
      PeSNAC1) or, ped-miR164b (OX-ped-miR164b) driven by the CaMV35S promoter were
      generated. OX-ped-miR164b plants showed similar phenotype of cuc2 mutants whose
      growth was seriously suppressed. Compared with Col-0, sense OX-PeSNAC1 plants
      grew rapidly and flowered earlier, whereas antisense plants grew slowly and
      exhibited delayed flowering. Sense OX-PeSNAC1 plants had the greatest number of
      lateral roots, while antisense OX-PeSNAC1 and OX-ped-miR164b plants had fewer
      lateral roots than Col-0. Under NaCl and PEG6000 stresses, survival rates were
      higher and F v/F m values declined more slowly in sense OX-PeSNAC1 plants than in
      Col-0, with lower survival rates and a more rapid decrease in F v/F m values
      conversely observed in antisense OX-PeSNAC1 and OX-ped-miR164b plants. These
      findings indicated that ped-miR164b-targeted PeSNAC1 may play key roles in plant
      development and tolerance to salinity and drought stresses.

PMID- 27021382
TI  - The Populus trichocarpa PtHSP17.8 involved in heat and salt stress tolerances.
AB  - KEY MESSAGE: PtHSP17.8 was regulated by various abiotic stresses. Overexpression
      of PtHSP17.8 enhanced the tolerance to heat and salt stresses through maintain
      ROS homeostasis and cooperate with stress-related genes in Arabidopsis. Small
      heat shock proteins (sHSPs) play important roles in response to diverse biotic
      and abiotic stresses, especially in heat tolerance. However, limited information
      is available on the stress tolerance roles of sHSPs in woody species. To explore
      the function of sHSPs in poplar, we isolated and characterized PtHSP17.8 from
      Populus trichocarpa. Phylogenetic analysis and subcellular localization revealed
      that PtHSP17.8 was a cytosolic class I sHSP. The gene expression profile of
      PtHSP17.8 in various tissues showed that it was significantly accumulated in stem
      and root, which was consistent with the GUS expression pattern driven by promoter
      of PtHSP17.8. The expression of PtHSP17.8 could be induced by various abiotic
      stresses and significantly activated by heat stress. Overexpression of PtHSP17.8
      enhanced the tolerance to heat and salt stresses in Arabidopsis. The seedling
      survival rate, root length, relative water content, antioxidative enzyme
      activities, proline, and soluble sugar content were increased in transgenic
      Arabidopsis under heat and salt stresses, but not in normal condition. The co
      expression network of PtHSP17.8 were constructed and demonstrated many stress
      responsive genes included. The stress-related genes in the co-expression network
      were up-regulated in the PtHSP17.8 overexpression seedlings. These results
      suggest that PtHSP17.8 confers heat and salt tolerances in plants.

PMID- 27021383
TI  - Identification, isolation and expression analysis of eight stress-related R2R3
      MYB genes in tartary buckwheat (Fagopyrum tataricum).
AB  - KEY MESSAGE: Eight R2R3 - MYB genes in tartary buckwheat were identified, and
      their expression patterns were comprehensively analyzed, which reveals role in
      plant response to abiotic stresses. The proteins of the R2R3-MYB superfamily play
      key roles in the growth and development processes as well as defense responses in
      plants. However, their characteristics and functions have not been fully
      investigated in tartary buckwheat (Fagopyrum tataricum), a strongly abiotic
      resistant coarse cereal. In this article, eight tartary buckwheat R2R3-MYB genes
      were isolated with full-length cDNA and DNA sequences. Phylogenetic analysis of
      the members of the R2R3-MYB superfamily between Arabidopsis and tartary buckwheat
      revealed that the assumed functions of the eight tartary buckwheat R2R3-MYB
      proteins are divided into five Arabidopsis functional subgroups that are involved
      in abiotic stress. Expression analysis during abiotic stress and exogenous
      phytohormone treatments identified that the eight R2R3-MYB genes responded to one
      or more treatments. This study is the first comprehensive analysis of the R2R3
      MYB gene family in tartary buckwheat under abiotic stress.

PMID- 27021384
TI  - A multifunctional CT technology: Reality or illusion for patient risk assessment?
AB  - A high-speed, multi-slice coronary computed tomography (CT) imaging has emerged
      as a promising or clinically available multifunctional technique for the
      assessment of myocardial ischemia, viability, ischemia-induced cardiac
      dysfunction, and coronary atherosclerotic alterations in patients with suspected
      or known coronary artery disease. Despite several technical issues remain to be
      resolved, cardiac CT imaging will have a reality as a multifunctional modality
      for guiding physicians in better decision-making for favorable clinical outcomes
      in patients with suspected coronary artery disease, provided that this imaging
      technology can contribute to characterization and localization of high-risk
      coronary atherosclerosis in combination with the quantitative evaluation of
      functional myocardial ischemia.

PMID- 27021385
TI  - The effect of coronary revascularization on regional myocardial blood flow as
      assessed by stress positron emission tomography.
AB  - OBJECTIVES: We examined whether regional improvement in stress myocardial blood
      flow (sMBF) following angiography-guided coronary revascularization depends on
      the existence of a perfusion defect on positron emission tomography (PET).
      BACKGROUND: Percent stenosis on coronary angiography often is the main factor
      when deciding whether to perform revascularization, but it does not reliably
      relate to maximum sMBF. PET is a validated method of assessing sMBF. METHODS: 19
      patients (79% M, 65 +/- 12 years) underwent PET stress before and after
      revascularization (17 PCI, 2 CABG). Pre- and post-revascularization sMBF for each
      left ventricular quadrant (anterior, septal, lateral, and inferior) was
      stratified by the presence or absence of a baseline perfusion defect on PET and
      whether that region was revascularized. RESULTS: Intervention was performed on 40
      of 76 quadrants. When a baseline perfusion defect existed in a region that was
      revascularized (n = 26), post-revascularization flow increased by 0.6 +/- 0.7
      cc/min/g (1.2 +/- 0.4 vs 1.7 +/- 0.8, P < 0.001). When no defect existed but
      revascularization was performed (n = 14), sMBF did not change significantly (1.7
      +/- 0.3 vs 1.5 +/- 0.4 cc/min/g, P = 0.16). In regions without a defect that were
      not revascularized (n = 29), sMBF did not significantly change (2.0 +/- 0.6 vs
      1.9 +/- 0.7, P = 0.7). CONCLUSIONS: When a stress-induced perfusion defect exists
      on PET, revascularization improves sMBF in that region. When there is no such
      defect, sMBF shows no net change, whether or not intervention is performed in
      that area. PET stress may be useful for identifying areas of myocardium that
      could benefit from revascularization, and also areas in which intervention is
      unlikely to yield improvement in myocardial blood flow.

PMID- 27021386
TI  - Informed consent in the ethics of responsibility as stated by Emmanuel Levinas.
AB  - In this paper we analyze some of the major difficulties of informed consent (IC).
      We consider insufficient to base IC on the principle of autonomy. We must not
      forget that the patient may be in a situation of extreme vulnerability and the
      good doctor should assume a degree of commitment and responsibility with his/her
      decisions. Our aim is to introduce the ethics of responsibility of Levinas in
      practice and theory of IC in order to generate a beneficent medical practice in
      which the supervision and overseeing of the patient do not undermine his/her
      autonomy. 

PMID- 27021387
TI  - Dental MRI using wireless intraoral coils.
AB  - Currently, the gold standard for dental imaging is projection radiography or cone
      beam computed tomography (CBCT). These methods are fast and cost-efficient, but
      exhibit poor soft tissue contrast and expose the patient to ionizing radiation (X
      rays). The need for an alternative imaging modality e.g. for soft tissue
      management has stimulated a rising interest in dental magnetic resonance imaging
      (MRI) which provides superior soft tissue contrast. Compared to X-ray imaging,
      however, so far the spatial resolution of MRI is lower and the scan time is
      longer. In this contribution, we describe wireless, inductively-coupled intraoral
      coils whose local sensitivity enables high resolution MRI of dental soft tissue.
      In comparison to CBCT, a similar image quality with complementary contrast was
      obtained ex vivo. In-vivo, a voxel size of the order of 250 ? 250 ? 500 MUm(3)
      was achieved in 4 min only. Compared to dental MRI acquired with clinical
      equipment, the quality of the images was superior in the sensitive volume of the
      coils and is expected to improve the planning of interventions and monitoring
      thereafter. This method may enable a more accurate dental diagnosis and avoid
      unnecessary interventions, improving patient welfare and bringing MRI a step
      closer to becoming a radiation-free alternative for dental imaging.

PMID- 27021388
TI  - Chronic disease in the ethnic minority and migrant groups: time for a paradigm
      shift in Europe.

PMID- 27021389
TI  - Cadaver-based training is superior to simulation training for cricothyrotomy and
      tube thoracostomy.
AB  - Emergency medicine (EM) training mandates that residents be able to competently
      perform low-frequency critical procedures upon graduation. Simulation is the main
      method of training in addition to clinical patient care. Access to cadaver-based
      training is limited due to cost and availability. The relative fidelity and
      perceived value of cadaver-based simulation training is unknown. This pilot study
      sought to describe the relative value of cadaver training compared to simulation
      for cricothyrotomy and tube thoracostomy. To perform a pilot study to assess
      whether there is a significant difference in fidelity and educational experience
      of cadaver-based training compared to simulation training. To understand how
      important this difference is in training residents in low-frequency procedures.
      Twenty-two senior EM residents (PGY3 and 4) who had completed standard simulation
      training on cricothyrotomy and tube thoracostomy participated in a formalin-fixed
      cadaver training program. Participants were surveyed on the relative fidelity of
      the training using a 100 point visual analogue scale (VAS) with 100 defined as
      equal to performing the procedure on a real patient. Respondents were also asked
      to estimate how much the cadaveric training improved the comfort level with
      performing the procedures on a scale between 0 and 100 %. Open-response feedback
      was also collected. The response rate was 100 % (22/22). The average fidelity of
      the cadaver versus simulation training was 79.9 +/- 7.0 vs. 34.7 +/- 13.4 for
      cricothyrotomy (p < 0.0001) and 86 +/- 8.6 vs. 38.4 +/- 19.3 for tube
      thoracostomy (p < 0.0001). Improvement in comfort levels performing procedures
      after the cadaveric training was rated as 78.5 +/- 13.3 for tube thoracostomy and
      78.7 +/- 14.3 for cricothyrotomy. All respondents felt this difference in
      fidelity to be important for procedural training with 21/22 respondents
      specifically citing the importance of superior landmark and tissue fidelity
      compared to simulation training. Cadaver-based training provides superior
      landmark and tissue fidelity compared to simulation training and may be a
      valuable addition to EM residency training for certain low-frequency procedures.

PMID- 27021390
TI  - A new paradigm for examining the correlates of aerobic, strength, and combined
      exercise: an application to gynecologic cancer survivors.
AB  - PURPOSE: Almost all exercise guidelines recommend both aerobic and strength
      exercise, however, few studies have simultaneously examined the correlates of
      meeting both exercise guidelines. Here, we propose a new paradigm that calls on
      researchers to examine not only the correlates of meeting the various exercise
      guidelines versus no guideline but also the correlates of meeting the combined
      guidelines versus one guideline and meeting one guideline versus the other
      guideline. METHODS: A random sample of 621 gynecologic cancer survivors located
      in Alberta, Canada, completed a mailed questionnaire. RESULTS: A multivariate
      multinomial logistic regression analysis indicated that (a) meeting only the
      aerobic exercise guideline compared to neither guideline was associated with
      younger age, social drinking, healthy weight, better general health, and no
      comorbidities; (b) meeting only the strength exercise guideline compared to
      neither guideline was associated with social drinking and being healthy weight;
      (c) meeting the combined exercise guideline compared to neither guideline was
      associated with social drinking, being healthy weight, and better general health;
      (d) meeting the aerobic guideline only compared to the strength guideline only
      was associated with younger age and better general health; and (e) few correlates
      distinguished between meeting the combined guidelines compared to a single
      guideline. CONCLUSIONS: Demographic and health variables are associated with
      meeting the various exercise guidelines versus no guideline but they are not
      associated with meeting the combined exercise guidelines versus a single
      guideline or meeting one guideline versus the other guideline. Application of
      this new paradigm to cancer survivors is encouraged.

PMID- 27021391
TI  - Engaging Patients as Partners in Developing Patient-Reported Outcome Measures in
      Cancer-A Review of the Literature.
AB  - PURPOSE: Tools to collect patient-reported outcome measures (PROMs) are
      frequently used in the healthcare setting to collect information that is most
      meaningful to patients. Due to discordance among how patients and healthcare
      providers rank symptoms that are considered most meaningful to the patient,
      engagement of patients in the development of PROMs is extremely important. This
      review aimed to identify studies that described how patients are involved in the
      item generation stage of cancer-specific PROM tools developed for cancer
      patients. METHODS: A literature search was conducted using keywords relevant to
      PROMs, cancer, and patient engagement. A manual search of relevant reference
      lists was also conducted. Inclusion criteria stipulated that publications must
      describe patient engagement in the item generation stage of development of cancer
      specific PROM tools. Results were excluded if they were duplicate findings or non
      English. RESULTS: The initial search yielded 230 publications. After removal of
      duplicates and review of publications, 6 were deemed relevant. Fourteen
      additional publications were retrieved through a manual search of references from
      relevant publications. A total of 13 unique PROM tools that included patient
      input in item generation were identified. The most common method of patient
      engagement was through qualitative interviews or focus groups. CONCLUSIONS:
      Despite recommendations from international groups and the emphasized importance
      of incorporating patient feedback in all stages of development of PROMs, few
      unique tools have incorporated patient input in item generation of cancer
      specific tools. Moving forward, a framework of best practices on how to best
      engage patients in developing PROMs is warranted to support high-quality patient
      centered care.

PMID- 27021392
TI  - Emotion regulation mediates the relationship between personality and sleep
      quality.
AB  - OBJECTIVE: Despite a long history of interest in personality as well as in the
      mechanisms that regulate sleep, the relationship between personality and sleep is
      not yet well understood. The purpose of this study was to explore how personality
      affects sleep. DESIGN: The present cross-sectional study, based on a sample of
      1291 participants with a mean age of 31.16 years (SD = 12.77), investigates the
      impact of personality styles, assessed by the Personality Adjectives Checklist
      (PACL), on subjective sleep quality, as well as the possible mediation of this
      relationship by dispositional emotion regulation (ER) styles. RESULTS: The
      dispositional use of suppression was a quite consistent predictor of poor
      subjective sleep quality for individuals scoring high on Confident, Cooperative
      or Introversive personality traits, but low on Respectful personality traits.
      Although a positive relationship between reappraisal and subjective sleep quality
      was found, there was only little evidence for a relationship between the assessed
      personality styles and the use of cognitive reappraisal. CONCLUSION: The present
      results indicate that in the evaluation of subjective sleep, the impact of
      personality and ER processes, such as emotion suppression, should be taken into
      account.

PMID- 27021394
TI  - Mitigating effect of chrysin loaded solid lipid nanoparticles against Amyloid
      beta25-35 induced oxidative stress in rat hippocampal region: An efficient
      formulation approach for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia. Amyloid-beta25
      35 (Abeta25-35), a well-established neurotoxicant, is reported to be involved in
      the etiology of AD. Chrysin (CN) with its wide range of biological activities in
      terms of reversing the neuronal damage once induced is limited due to its
      compromised bioavailability. Solid lipid nanoparticles (SLNs) on the other hand
      due to its improved protein stability, avoids proteolytic degradation, as well as
      sustained release of the incorporated molecules could be widely applied as a drug
      delivery vehicle. Hence, in the present investigation, we prepared CN loaded SLNs
      (CN-SLNs) and investigated its therapeutic role in alleviating Abeta25-35
      administered neuronal damage. All the antioxidant enzymes and non-antioxidant
      enzyme in hippocampus were reduced significantly (P<0.01) in the Abeta25-35
      injected group, whereas lipid peroxidation and acetylcholine esterase were
      increased significantly (P<0.01). These changes were restored significantly
      (P<0.01) by CN-SLNs (5mg/kg and 10mg/kg) and (P<0.05) by free CN (50mg/kg and
      100mg/kg). Abeta25-35 also resulted in poor memory retention in behavioral tasks
      and histopathological sections of the hippocampal region showed the extent of
      neuronal loss which was thereby restored back on treatment with CN-SLNs and free
      CN. Our findings demonstrate that the therapeutic efficacy of CN could be
      attained at lower dose and also its oral bioavailability could be increased by
      encapsulating CN in SLNs. Thus the results suggest that CN-SLNs could be used as
      a potential therapeutic and a brain targeting strategy to combat the global
      burden of Alzheimer's disease. 

PMID- 27021395
TI  - Pancreatic neuroendocrine tumors: Challenges in an underestimated disease.
AB  - Pancreatic neuroendocrine tumours (PanNETs) are considered a relatively unusual
      oncologic entity. Due to its relative good prognosis, surgery remains the goal
      standard therapy not only in localized disease but also in the setting of locally
      or metastatic disease. Most of the patients are diagnosed in metastatic scenario,
      where multidisciplinary approach based on surgery, chemotherapies, liver-directed
      and/or molecular targeted therapies are commonly used. Owing to a deeper
      molecular knowledge of this disease, these targeted therapies are nowadays widely
      implemented, being the likely discovery of predictive biomarkers that would allow
      its use in other settings. This review is focused on describing the different
      classifications, etiology, prognostic biomarkers and multidisciplinary approaches
      that are typically used in PanNET. 

PMID- 27021396
TI  - Surfactin, Iturin, and Fengycin Biosynthesis by Endophytic Bacillus sp. from
      Bacopa monnieri.
AB  - Endophytic microorganisms which are ubiquitously present in plants may colonize
      intracellularly or intercellularly without causing any diseases. By living within
      the unique chemical environment of a host plant, they produce a vast array of
      compounds with a wide range of biological activities. Because of this, natural
      products of endophytic origin have been exploited for antimicrobial, antiviral,
      anticancer, and antioxidant properties. Also, they can be considered to function
      as an efficient microbial barrier to protect plants from various pathogens. In
      the present study, endophytic bacterium BmB 9 with antifungal and antibacterial
      activity isolated from the stem tissue of Bacopa monnieri was studied for the
      molecular and chemical basis of its activity. PCR-based genome mining for various
      biosynthetic gene clusters proved the presence of surfactin, iturin, and type I
      polyketide synthase (PKS) genes in the isolate. The LC-MS/MS based analysis of
      the extract further confirmed the production of surfactin derivatives (M + H(+)
      1008.6602, 1022.6755), iturin (M + H(+)-1043.5697), and fengycin (M + H(+)
      1491.8195, 1477.8055) by the selected bacterial isolate. The 16S rDNA sequence
      similarity based analysis identified the isolate BmB 9 as Bacillus sp. with 100 %
      identity to Bacillus sp. LCF1 (KP257289).

PMID- 27021397
TI  - Application of water-soluble nanofilters for collection of airborne Mycobacterium
      tuberculosis DNA in hospital wards.
AB  - A simple inexpensive technique for collection of airborne biomarkers of
      nosocomial infections is described. Biomarkers were collected on water-soluble
      electrospun nanofilters attached to a household vacuum cleaner from 6-10m(3) of
      air in 10-15min within several wards of a tuberculosis clinic. Filters were then
      dissolved in water and tested for the presence of the IS6110 and regX3 genes of
      Mycobacterium tuberculosis (MTB) using real-time polymerase chain reaction. It
      was demonstrated that trace amounts of airborne MTB DNA (>3gene copies/m(3)) were
      always present in the air and on the surfaces in the wards occupied with
      tuberculosis patients having positive smear tests. 

PMID- 27021398
TI  - Hand soap contamination by Pseudomonas aeruginosa in a tertiary care hospital: no
      evidence of impact on patients.
AB  - BACKGROUND: During an environmental investigation of Pseudomonas aeruginosa in
      intensive care units, the liquid hand soap was found to be highly contaminated
      (up to 8 * 10(5)cfu/g) with this pathogen. It had been used over the previous
      five months and was probably contaminated during manufacturing. AIM: To evaluate
      the burden of this contamination on patients by conducting an epidemiological
      investigation using molecular typing combined with whole genome sequencing (WGS).
      METHODS: P. aeruginosa isolates from clinical specimens were analysed by double
      locus sequence typing (DLST) and compared with isolates recovered from the soap.
      Medical charts of patients infected with a genotype identical to those found in
      the soap were reviewed. WGS was performed on soap and patient isolates sharing
      the same genotype. FINDINGS: P. aeruginosa isolates (N = 776) were available in
      358/382 patients (93.7%). Only three patients (0.8%) were infected with a
      genotype found in the soap. Epidemiological investigations showed that the first
      patient was not exposed to the soap, the second could have been exposed, and the
      third was indeed exposed. WGS showed a high number of core single nucleotide
      polymorphism differences between patients and soap isolates. No close genetic
      association was observed between soap and patient isolates, ruling out the
      hypothesis of transmission. CONCLUSION: Despite a highly contaminated soap, the
      combined investigation with DLST and WGS ruled out any impact on patients. Hand
      hygiene performed with alcohol-based solution for >15 years was probably the main
      reason. However, such contamination represents a putative reservoir of pathogens
      that should be avoided in the hospital setting.

PMID- 27021399
TI  - Physical and composition characteristics of clinical secretions compared with
      test soils used for validation of flexible endoscope cleaning.
AB  - AIM: To determine which simulated-use test soils met the worst-case organic
      levels and viscosity of clinical secretions, and had the best adhesive
      characteristics. METHODS: Levels of protein, carbohydrate and haemoglobin, and
      vibrational viscosity of clinical endoscope secretions were compared with test
      soils including ATS, ATS2015, Edinburgh, Edinburgh-M (modified), Miles, 10% serum
      and coagulated whole blood. ASTM D3359 was used for adhesion testing. Cleaning of
      a single-channel flexible intubation endoscope was tested after simulated use.
      RESULTS: The worst-case levels of protein, carbohydrate and haemoglobin, and
      viscosity of clinical material were 219,828MUg/mL, 9296MUg/mL, 9562MUg/mL and
      6cP, respectively. Whole blood, ATS2015 and Edinburgh-M were pipettable with
      viscosities of 3.4cP, 9.0cP and 11.9cP, respectively. ATS2015 and Edinburgh-M
      best matched the worst-case clinical parameters, but ATS had the best adhesion
      with 7% removal (36.7% for Edinburgh-M). Edinburgh-M and ATS2015 showed similar
      soiling and removal characteristics from the surface and lumen of a flexible
      intubation endoscope. CONCLUSIONS: Of the test soils evaluated, ATS2015 and
      Edinburgh-M were found to be good choices for the simulated use of endoscopes, as
      their composition and viscosity most closely matched worst-case clinical
      material.

PMID- 27021400
TI  - Prevalence of multi-drug-resistant organism carriage in pregnant women.

PMID- 27021401
TI  - School District Policies and Adolescents' Soda Consumption.
AB  - PURPOSE: Sugar-sweetened beverages (SSBs) are a significant source of calories
      and added sugars for youth ages 14-18 years in the United States. This study
      examined the relationship between district-level policies and practices and
      students' consumption of regular soda, one type of SSB, in 12 large urban school
      districts. METHODS: Data from the 2012 School Health Policies and Practices Study
      and 2013 Youth Risk Behavior Surveillance System were linked by district. The
      outcome variable was soda consumption and exposure variables were district
      policies. We used multivariable logistic regression analyses to calculate
      adjusted odds ratios (AORs) and 95% confidence intervals (CIs) after controlling
      for student characteristics and district free/reduced-price meal eligibility.
      RESULTS: About 18% of students reported consuming regular soda at least once per
      day. Most districts required high schools to have nutrition education, maintain
      closed campuses, and required/recommended that schools restrict promotional
      products and sale of beverages. Fewer districts required/recommended that schools
      offer healthful alternative beverages. Students in districts that restricted
      promotional products had lower odds of regular soda consumption (AOR = .84, 95%
      CI = .71-1.00), as did students in districts that restricted access to SSBs and
      offered healthful beverages when other beverages were available (AOR = .72, 95%
      CI = .54-.93, AOR = .76, 95% CI = .63-.91). CONCLUSIONS: This study demonstrates
      that certain district-level policies are associated with student consumption of
      regular soda. These findings add to a growing consensus that policies and
      practices that influence the availability of healthier foods and beverages are
      needed across multiple settings.

PMID- 27021402
TI  - The Sensitivity of Adolescent Hearing Screens Significantly Improves by Adding
      High Frequencies.
AB  - PURPOSE: One in 6 US adolescents has high-frequency hearing loss, often related
      to hazardous noise. Yet, the American Academy of Pediatrics (AAP) hearing screen
      (500, 1,000, 2,000, 4,000 Hertz) primarily includes low frequencies (<3,000
      Hertz). Study objectives were to determine (1) sensitivity and specificity of the
      AAP hearing screen for adolescent hearing loss and (2) if adding high frequencies
      increases sensitivity, while repeat screening of initial referrals reduces false
      positive results (maintaining acceptable specificity). METHODS: Eleventh graders
      (n = 134) participated in hearing screening (2013-2014) including "gold-standard"
      sound-treated booth testing to calculate sensitivity and specificity. RESULTS: Of
      the 43 referrals, 27 (63%) had high-frequency hearing loss. AAP screen
      sensitivity and specificity were 58.1% (95% confidence interval 42.1%-73.0%) and
      91.2% (95% confidence interval 83.4-96.1), respectively. Adding high frequencies
      (6,000, 8,000 Hertz) significantly increased sensitivity to 79.1% (64.0%-90.0%; p
      = .003). Specificity with repeat screening was 81.3% (71.8%-88.7%; p = .003).
      CONCLUSIONS: Adolescent hearing screen sensitivity improves with high
      frequencies. Repeat testing maintains acceptable specificity.

PMID- 27021403
TI  - Remote control over folding by light.
AB  - Integrating stimulus-responsive components into macromolecular architectures is a
      versatile strategy to create smart materials that can be controlled by external
      stimuli and even adapt to their environment. Helical foldamers, which are
      omnipresent in Nature and display well-defined yet dynamic structures, serve as
      an ideal platform to integrate photoswitches to modulate their conformations by
      light. This feature article summarizes the development of photoswitchable
      foldamers, focussing on various design approaches that incorporate the
      photoswitches either at the side chains, as tethered loops, or directly in the
      main chain. Based on the emerging insight into the folding-switching relationship
      more advanced molecular designs should enable the development of photoresponsive
      foldamers with high sensitivity to control and power functional macromolecular
      and supramolecular systems.

PMID- 27021404
TI  - Mast Cells Regulate Epidermal Barrier Function and the Development of Allergic
      Skin Inflammation.
AB  - Atopic dermatitis is a chronic inflammatory skin disease characterized by
      infiltration of eosinophils, T helper cells, and mast cells. The role of mast
      cells in atopic dermatitis is not completely understood. To define the effects of
      mast cells on skin biology, we observed that mast cells regulate the homeostatic
      expression of epidermal differentiation complex and other skin genes. Decreased
      epidermal differentiation complex gene expression in mice that genetically lack
      mast cells (Kit(W-sh/W-sh) mice) is associated with increased uptake of protein
      antigens painted on the skin by dendritic cells (DCs) compared with similarly
      treated wild-type mice, suggesting a protective role for mast cells in exposure
      to nominal environmental allergens. To test this further, we crossed Kit(W-sh/W
      sh) mice with signal transducer and activator of transcription 6 (i.e., Stat6) VT
      transgenic mice that develop spontaneous atopic dermatitis-like disease that is
      dependent on T helper cell 2 cytokines and is associated with high serum
      concentrations of IgE. We observed that Stat6VT * Kit(W-sh/W-sh) mice developed
      more frequent and more severe allergic skin inflammation than Stat6VT transgenic
      mice that had mast cells. Together, these studies suggest that mast cells
      regulate epidermal barrier function and have a potential protective role in the
      development of atopic dermatitis-like disease.

PMID- 27021405
TI  - Constitutive Autophagy and Nucleophagy during Epidermal Differentiation.
AB  - Epidermal keratinocytes migrate through the epidermis up to the granular layer
      where, on terminal differentiation, they progressively lose organelles and
      convert into anucleate cells or corneocytes. Our report explores the role of
      autophagy in ensuring epidermal function providing the first comprehensive
      profile of autophagy marker expression in developing epidermis. We show that
      autophagy is constitutively active in the epidermal granular layer where by
      electron microscopy we identified double-membrane autophagosomes. We demonstrate
      that differentiating keratinocytes undergo a selective form of nucleophagy
      characterized by accumulation of microtubule-associated protein light chain
      3/lysosomal-associated membrane protein 2/p62 positive autolysosomes. These
      perinuclear vesicles displayed positivity for histone interacting protein,
      heterochromatin protein 1alpha, and localize in proximity with Lamin A and B1
      accumulation, whereas in newborn mice and adult human skin, we report LC3 puncta
      coincident with misshaped nuclei within the granular layer. This process relies
      on autophagy integrity as confirmed by lack of nucleophagy in differentiating
      keratinocytes depleted from WD repeat domain phosphoinositide interacting 1 or
      Unc-51 like autophagy activating kinase 1. Final validation into a skin disease
      model showed that impaired autophagy contributes to the pathogenesis of
      psoriasis. Lack of LC3 expression in psoriatic skin lesions correlates with
      parakeratosis and deregulated expression or location of most of the autophagic
      markers. Our findings may have implications and improve treatment options for
      patients with epidermal barrier defects.

PMID- 27021406
TI  - Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit
      Bone.
AB  - Clinically, many nail disorders accompany bone deformities, but whether the two
      defects are causally related is under debate. To investigate the potential
      interactions between the two tissue types, we analyzed epithelial-specific beta
      catenin-deficient mice, in which nail differentiation is abrogated. These mice
      showed regression of not only the nail plate but also of the underlying digit
      bone. Characterization of these bone defects revealed active bone resorption,
      which is suppressed by Wnt activation in osteoblast and osteoclast precursors.
      Furthermore, we found that Wntless expression, essential for Wnt ligand
      secretion, was lacking in the beta-catenin-deficient nail epithelium and that
      genetic deletion of Wntless (Wls) in the nail epithelium led to the lack of Wnt
      activation in osteoblast and osteoclast precursors and subsequently led to
      defective regression of the underlying digit bone. Together, these data show that
      epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblast and
      osteoclast precursors, known to regulate bone homeostasis. These results reveal a
      critical role for the nail epithelium on the digit bone during homeostatic
      regeneration and show that Wnt/beta-catenin signaling is critical for this
      interaction.

PMID- 27021407
TI  - IL-36gamma Is Involved in Psoriasis and Allergic Contact Dermatitis.

PMID- 27021408
TI  - The Blood Donor Anxiety Scale: a six-item state anxiety measure based on the
      Spielberger State-Trait Anxiety Inventory.
AB  - BACKGROUND: Research demonstrates that anxiety elevates the risk of blood donors
      experiencing adverse events, which in turn deters the performance of repeat blood
      donations. Identifying donors suffering from heightened state anxiety is
      important to assess the impact of evidence-based interventions. This study
      analyzed the appropriateness of a shortened version of the state subscale of the
      State-Trait Anxiety Inventory (STAI) in a blood donation context. STUDY DESIGN
      AND METHODS: STAI-State questionnaire data were collected from two separate
      samples of Australian blood donors (n = 919 and n = 824 after cleaning).
      Responses to demographic, donation history, and adverse reaction questions were
      also obtained. Identification of items and analysis was performed systematically
      to assess and compare internal reliability and content, construct, convergent,
      and criterion validity of three potential short-form state anxiety scales.
      RESULTS: Of the three short-form scales tested, STAI-State six-item scale
      demonstrated the best metric properties with the least number of items across
      both sample groups. Cronbach's alpha was acceptable (alpha = 0.844 and alpha =
      0.820), correlated positively with the original measure (r = 0.927 and r = 0.931)
      and criterion-related variables, and maintained the two-dimension factorial
      structure of the original measure. CONCLUSION: The six-item short version of the
      STAI-State subscale presented the most reliable and valid scale for use with
      blood donors. A validated donor anxiety tool provides a standardized assessment
      and record of donor anxiety to gauge the effectiveness of ongoing efforts to
      enhance the donation experience.

PMID- 27021409
TI  - Celiac Disease and Risk of Autoimmune Disorders: A Population-Based Matched Birth
      Cohort Study.
AB  - OBJECTIVES: To estimate the relative risk of developing type 1 diabetes mellitus
      (T1DM) and autoimmune thyroid disease in children with celiac disease (CD). STUDY
      DESIGN: A matched cohort design with linkage of administrative data was adopted.
      A total of 1215 cases of CD and 6075 references matched by sex and year of birth
      born in Friuli Venezia Giulia Region (Italy) between 1989 and 2011 were included.
      Cox regression models were used to estimate hazard ratios (HRs) for autoimmune
      diseases in patients with CD compared with references, stratified by sex and age
      at diagnosis. RESULTS: Individuals with CD had an increased risk of subsequent
      hypothyroidism (HR 4.64 [95% CI 2.88-7.46]) and T1DM (HR 2.50 [95% CI 0.94
      6.66]), the latter not statistically significant. Risk of hypothyroidism was
      higher in males (HR 20.00; 95% CI 5.64-70.87) than females (HR 3.21; 95% CI 1.85
      5.57) (P value <.01). No differences were observed between males and females
      risks for diabetes or age at CD diagnosis. The small number of hyperthyroidism
      cases identified precluded any statistical analysis. CONCLUSIONS: Children and
      youth with CD are at increased risk of developing autoimmune hypothyroidism and
      to some extent T1DM. This suggests the need for surveillance of children with CD
      in order to timely detect the onset of such comorbidities.

PMID- 27021410
TI  - Receptor occupancy by flow cytometry.

PMID- 27021412
TI  - Statements from Youth in Legal Contexts: Effects of Consistency, Legal Role, and
      Age.
AB  - Jurors are often asked to evaluate statements provided by young victims,
      witnesses, and suspects. When, over time, youths' statements contain inconsistent
      information or recantations of prior statements, jurors face a difficult task in
      evaluating the validity of the initial claim. The underlying reasons for
      inconsistencies and recantation of young people's statements, particularly in
      cases of child sexual abuse, have been debated. Of primary interest here is
      whether inconsistencies (e.g., recantation) are evaluated differently by fact
      finders depending on the youth's age and role in a legal case. The current study
      examined effects of consistency of juvenile statements, legal role, and age on
      perceptions of testimony in a child sexual abuse investigation. Participants (N =
      693) read vignettes describing child sexual abuse in which consistency of a
      follow-up statement (consistent, inconsistent, recanted), legal role (victim,
      witness, suspect), and age (10 years, 16 years) of the juvenile providing
      testimony were manipulated. The results revealed that judgments of initial
      statement quality, blameworthiness, and guilt were dependent on the consistency
      of follow-up statements and on the interactive effects of a juvenile's legal role
      and age. The current study has theoretical implications for understanding juror
      decision-making and practical implications for legal professionals and fact
      finders evaluating youths' statements. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27021411
TI  - Paeonol and danshensu combination attenuates apoptosis in myocardial infarcted
      rats by inhibiting oxidative stress: Roles of Nrf2/HO-1 and PI3K/Akt pathway.
AB  - Paeonol and danshensu is the representative active ingredient of traditional
      Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae,
      respectively. Paeonol and danshensu combination (PDSS) has putative
      cardioprotective effects in treating ischemic heart disease (IHD). However, the
      evidence for the protective effect is scarce and the pharmacological mechanisms
      of the combination remain unclear. The present study was designed to investigate
      the protective effect of PDSS on isoproterenol (ISO)-induced myocardial
      infarction in rats and to elucidate the potential mechanism. Assays of creatine
      kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS
      significantly prevented myocardial injury induced by ISO. The ISO-induced
      profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and
      caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in
      myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced
      the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS
      increased phosphorylated PI3K and Akt, which may in turn activate antioxidative
      and antiapoptotic signaling events in rat. These present findings demonstrated
      that PDSS exerts significant cardioprotective effects against ISO-induced
      myocardial infarction in rats. The protective effect is, at least partly, via
      activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival
      signaling pathway. 

PMID- 27021413
TI  - Staurosporine allows dystrophin expression by skipping of nonsense-encoding exon.
AB  - BACKGROUND: Antisense oligonucleotides that induce exon skipping have been
      nominated as the most plausible treatment method for dystrophin expression in
      dystrophin-deficient Duchenne muscular dystrophy. Considering this therapeutic
      efficiency, small chemical compounds that can enable exon skipping have been
      highly awaited. In our previous report, a small chemical kinase inhibitor, TG003,
      was shown to enhance dystrophin expression by enhancing exon skipping. PURPOSE:
      Staurosporine (STS), a small chemical broad kinase inhibitor, was examined for
      enhanced skipping of a nonsense-encoding dystrophin exon. METHODS: STS was added
      to culture medium of HeLa cells transfected with minigenes expressing wild-type
      or mutated exon 31 with c.4303G>T (p.Glu1435X), and the resulting mRNAs were
      analyzed by RT-PCR amplification. Dystrophin mRNA and protein were analyzed in
      muscle cells treated with STS by RT-PCR and western blotting, respectively.
      RESULTS: STS did not alter splicing of the wild-type minigene. In the mutated
      minigene, STS increased the exon 31-skipped product. A combination of STS and
      TG003 did not significantly increase the exon 31-skipped product. STS enhanced
      skipping of exon 4 of the CDC-like kinase 1 gene, whereas TG003 suppressed it.
      Two STS analogs with selective kinase inhibitory activity did not enhance the
      mutated exon 31 skipping. When immortalized muscle cells with c.4303G>T in the
      dystrophin gene were treated with STS, skipping of the mutated exon 31 and
      dystrophin expression was enhanced. CONCLUSIONS: STS, a broad kinase inhibitor,
      was shown to enhance skipping of the mutated exon 31 and dystrophin expression,
      but selective kinase inhibitors did not.

PMID- 27021414
TI  - Genetically designed biomolecular capping system for mesoporous silica
      nanoparticles enables receptor-mediated cell uptake and controlled drug release.
AB  - Effective and controlled drug delivery systems with on-demand release and
      targeting abilities have received enormous attention for biomedical applications.
      Here, we describe a novel enzyme-based cap system for mesoporous silica
      nanoparticles (MSNs) that is directly combined with a targeting ligand via bio
      orthogonal click chemistry. The capping system is based on the pH-responsive
      binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic
      anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was
      genetically incorporated into CA. This UAA allowed for the site-specific bio
      orthogonal attachment of even very sensitive targeting ligands such as folic acid
      and anandamide. This leads to specific receptor-mediated cell and stem cell
      uptake. We demonstrate the successful delivery and release of the
      chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept
      provides a promising platform for the development of precisely controllable and
      highly modular theranostic systems. 

PMID- 27021415
TI  - Tuning supramolecular aurophilic structures: the effect of counterion, positive
      charge and solvent.
AB  - The synthesis of the cationic gold(i) complexes [Au(C[triple bond, length as m
      dash]CC5H4N)(CH3-PTA)]X (X = I, 1; X = OTf, 4), [Au(C[triple bond, length as m
      dash]CC5H4N-CH3)(PTA)]X (X = I, 2; X = OTf = 5; PTA = 1,3,5-triaza-7
      phosphatricyclo[3.3.1.13.7]decane) and [Au(C[triple bond, length as m-dash]CC5H4N
      CH3)(DAPTA)]X (X = I, 3; X = OTf = 6, DAPTA = 3,7-diacetyl-1,3,7-triaza-5
      phosphabicyclo[3.3.1]nonane) results in cationic complexes with unexpected
      supramolecular assemblies in water ranging from rod-like structures (1) to
      vesicles (2 and 3) and square-like structures (5 and 6). These morphologies are
      completely different from the fibers previously obtained with their parent
      neutral complexes [Au(C[triple bond, length as m-dash]C5H4N)(PTA)] and
      [Au(C[triple bond, length as m-dash]C5H4N)(DAPTA)]. Nevertheless, the
      introduction of triflate as a counterion in 1 (complex 4) gives rise to the
      formation of a highly soluble complex in water which does not display any
      significant aggregation in solution. These results reveal the importance of the
      introduction of a positive charge on global supramolecular assemblies and how the
      counterion can also modify the resulting package. Interestingly, we have also
      proved that the aggregation of complexes 2, 3, 5 and 6 is also affected by the
      solvent with direct influence on their absorption and emission properties and the
      global morphology of the aggregates.

PMID- 27021416
TI  - Is there relationship between dynamic volumes of pulmonary function and cardiac
      workload (maximal oxygen uptake) in young athletes?

PMID- 27021417
TI  - Gold nanoparticle surface  functionalization: mixed monolayer versus  hetero
      bifunctional peg linker.
AB  - To create a clinically relevant gold nanoparticle (AuNP) treatment, the surface
      must be functionalized with multiple ligands such as drugs, antifouling agents
      and targeting moieties. However, attaching several ligands of differing
      chemistries and lengths, while ensuring they all retain their biological
      functionality remains a challenge. This review compares the two most widely
      employed methods of surface cofunctionalization, namely mixed monolayers and
      hetero-bifunctional linkers. While there are numerous in vitro studies
      successfully utilizing both surface arrangements, there is little consensus
      regarding their relative merits. Animal and preclinical studies have demonstrated
      the effectiveness of mixed monolayer functionalization and while some promising
      in vitro results have been reported for PEG linker capped AuNPs, any potential
      benefits of the approach are not yet fully understood.

PMID- 27021418
TI  - Do we need new antibiotics?
AB  - For several years, alarmist articles both in mass media and in the scientific
      community have reported an increase in antibiotic resistance, even citing an
      inability to treat patients infected with multidrug-resistant bacteria (MDR)
      responsible for high mortality worldwide. In this review we summarize and discuss
      the key points associated with the reality of (i) the existence of pandrug
      resistant bacteria, (ii) the increase of resistance worldwide, (iii) the link
      between resistance and death, and (iv) the need to develop new antibiotics. Data
      on antibiotic resistance in Europe for the main bacteria associated with invasive
      infections apparently demonstrate that apart from Klebsiella pneumoniae, which is
      resistant to carbapenems in three countries (Romania, Italy and Greece), the
      level of resistance to three or more classes of antibiotics (defined as MDR
      phenotype) has remained low and stable over the last 5 years and that therapeutic
      options exist both for reference antibiotics and for old antibiotics. The
      clinical outcome of patients infected by MDR bacteria remains controversial and
      death rates attributable to MDR bacteria versus non-MDR bacteria are still
      debated. The arsenal of antibiotics currently available (including 'old
      antibiotics') suffices for facing the waves of emergence of new bacterial
      resistance and should be considered as a World Heritage. This heritage should be
      managed in a non-profit model with international regulatory approval. 

PMID- 27021419
TI  - Plasmid-mediated colistin resistance: an additional antibiotic resistance menace.

PMID- 27021420
TI  - Is there a terrible issue with bacterial resistance: pro-con.

PMID- 27021421
TI  - Declining mortality among hospitalized patients with community-acquired
      pneumonia.
AB  - Little information is available on the changes over time in community-acquired
      pneumonia (CAP) management and their impact on 30-day mortality in hospitalized
      patients. We performed a prospective, observational study of non-severely
      immunosuppressed hospitalized adults with CAP from 1995 to 2014. A total of 4558
      patients were included. Thirty-day mortality decreased from 9.6% in the first
      study period (1995-99) to 4.1% in the last period (2010-14); with a progressive
      downward trend (-0.2% death/year; p for trend = 0.003). Over time, patients were
      older (p 0.02), had more co-morbidities (p 0.037), more frequently presented
      severe illness according to the Pneumonia Severity Index (p <0.001) and septic
      shock (p <0.001), and more often required intensive care unit admission (p
      <0.001). Combination antibiotic therapy (p <0.001) and fluoroquinolone use (p
      <0.001) increased. Factors independently associated with 30-day mortality were
      increasing age (OR 1.04; 95% CI 1.03-1.05), co-morbidities (OR 1.48; 95% CI 1.04
      2.11), shock at admission (OR 4.95; 95% CI 3.49-7.00), respiratory failure (OR
      1.89; 95% CI 1.42-2.52), bacteraemia (OR 2.16; 95% CI 1.58-2.96), Gram-negative
      bacilli aetiology (OR 4.79; 95% CI 2.52-9.10) and fluoroquinolone use (OR 0.45;
      95% CI 0.29-0.71). When we adjusted for a propensity score to receive
      fluoroquinolones, the protective effect of fluoroquinolone use was not confirmed.
      In conclusion, 30-day mortality decreased significantly over time in hospitalized
      patients with CAP in spite of an upward trend in patient age and other factors
      associated with poor outcomes. Several changes in the management of CAP and a
      general improvement in global care over time may have caused the observed
      outcomes. 

PMID- 27021422
TI  - Intrapopulation variability in mutator prevalence among urinary tract infection
      isolates of Escherichia coli.
AB  - Bacteria with elevated mutation rates represent a risk factor for treatment
      failure and are often found with high frequency in clinical isolates from
      different sources. How this frequency reflects the among-population and within
      population proportion of hypermutators is unknown, despite its importance to the
      choice of antibiotic therapies that minimize the likelihood of resistance
      development. Here we screened for hypermutators among the urine of 80 patients
      with urinary tract infections, at an unprecedented resolution of 24 isolates per
      sample. We found hypermutators in four patients (5%), at frequencies ranging from
      4.2% to 62.5%. Molecular characterization revealed alterations in the oxidized
      guanine (GO) and methly-directed mistmatch repair (MMR) systems as the genetic
      basis of hypermutability. These observations suggest that mutators may be present
      in more patients than previously anticipated, at frequencies that are difficult
      to detect but still sufficient to impact on adaptation to antibiotics or the host
      environment. 

PMID- 27021423
TI  - Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent
      episodes of tuberculosis, Finland, 1995-2013.
AB  - Recurrent tuberculosis (TB) is caused by an endogenous re-activation of the same
      strain of Mycobacterium tuberculosis (relapse) or exogenous infection with a new
      strain (re-infection). Recurrence of TB in Finland was analysed in a population
      based, 19-year study, and genotyping was used to define relapse and re-infection.
      The M. tuberculosis isolates from patients with suspected relapse were further
      analysed by whole genome sequencing (WGS) to determine the number and type of
      mutations occurring in the bacterial genome between the first and second disease
      episodes. In addition, publicly available tools (PhyResSE and SpolPred) were used
      to predict drug resistance and spoligotype profile from the WGS data. Of the 8299
      notified TB cases, 48 (0.6%) patients had episodes classified as recurrent. Forty
      two patients had more than one culture-confirmed TB episode, and isolates from
      two episodes in 21 patients were available for genotyping. In 18 patients, the M.
      tuberculosis isolates obtained from the first and second TB episodes had
      identical spoligotypes. The WGS analysis of the 36 M. tuberculosis isolates from
      the 18 suspected relapse patients (average time between isolates 2.8 years)
      revealed 0 to 38 single nucleotide polymorphisms (median 1, mean 3.78) between
      the first and second isolate. There seemed to be no direct relation between the
      number of years between the two isolates, or treatment outcome, and the number of
      single nucleotide polymorphisms. The results suggest that the mutation rate may
      depend on multiple host-, strain- and treatment-related factors. 

PMID- 27021424
TI  - Characteristics and prognosis of pneumococcal endocarditis: a case-control study.
AB  - Case series have suggested that pneumococcal endocarditis is a rare disease,
      mostly reported in patients with co-morbidities but no underlying valve disease,
      with a rapid progression to heart failure, and high mortality. We performed a
      case-control study of 28 patients with pneumococcal endocarditis (cases), and 56
      patients with non-pneumococcal endocarditis (controls), not matched for sex and
      age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus
      10.7%; p <0.01), smoking (60.7% versus 21.4%; p <0.01), the absence of previously
      known valve disease (82.1% versus 60.7%; p 0.047), heart failure (64.3% versus
      23.2%; p <0.01) and shock (53.6% versus 23.2%; p <0.01) were more common in
      pneumococcal than in non-pneumococcal endocarditis. Cardiac surgery was required
      in 64.3% of patients with pneumococcal endocarditis, much earlier than in
      patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1
      +/- 18.2 versus 69.0 +/- 61.1 days). In-hospital mortality rates were similar
      (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive
      endocarditis requiring life-saving early cardiac surgery in most cases. 

PMID- 27021425
TI  - Multicentre study highlighting clinical relevance of new high-throughput
      methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.
AB  - Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in
      immunosuppressed patients. This multicentre study assessed the distribution
      frequencies of epidemiologically relevant genetic markers of P. jirovecii in
      different geographic populations from Portugal, the USA, Spain, Cuba and
      Mozambique, and the relationship between the molecular data and the geographical
      and clinical information, based on a multifactorial approach. The high-throughput
      typing strategy for P. jirovecii characterization consisted of DNA pooling using
      quantitative real-time PCR followed by multiplex-PCR/single base extension. The
      frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85,
      SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated
      in ten DNA pooled samples representing a total of 182 individual samples.
      Putative multilocus genotypes of P. jirovecii were shown to be clustered due to
      geographic differences but were also dependent on clinical characteristics of the
      populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with
      severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this
      genetic variant of P. jirovecii were significantly higher in patients with AIDS
      related PcP from Portugal and the USA than in the colonized patients from
      Portugal, and Spain, and children infected with P. jirovecii from Cuba or
      Mozambique, highlighting the importance of this haplotype, apparently associated
      with the severity of the disease and specific clinical groups. Patients from the
      USA and Mozambique showed higher rates of DHPS mutants, which may suggest the
      circulation of P. jirovecii organisms potentially related with trimethoprim
      sulfamethoxazole resistance in those geographical regions. This report assessed
      the worldwide distribution of P. jirovecii haplotypes and their epidemiological
      impact in distinct geographic and clinical populations. 

PMID- 27021426
TI  - Exploration of the P3 region of PEXEL peptidomimetics leads to a potent inhibitor
      of the Plasmodium protease, plasmepsin V.
AB  - The use of arginine isosteres is a known strategy to overcome poor membrane
      permeability commonly associated with peptides or peptidomimetics that possess
      this highly polar amino acid. Here, we apply this strategy to peptidomimetics
      that are potent inhibitors of the malarial protease, plasmepsin V, with the aim
      of enhancing their activity against Plasmodium parasites, and exploring the
      structure-activity relationship of the P3 arginine within the S3 pocket of
      plasmepsin V. Of the arginine isosteres trialled in the P3 position, we
      discovered that canavanine was the ideal and that this peptidomimetic potently
      inhibits plasmepsin V, efficiently blocks protein export and inhibits parasite
      growth. Structure studies of the peptidomimetics bound to plasmepsin V provided
      insight into the structural basis for the enzyme activity observed in vitro and
      provides further evidence why plasmepsin V is highly sensitive to substrate
      modification. 

PMID- 27021427
TI  - Decidual endothelium, Notch1 and TGFbeta, gatekeepers for Treg accumulation at
      the maternal-fetal interface.

PMID- 27021428
TI  - Diagnostic performance of a semiconductor gamma-camera system as studied by
      multicenter registry.
AB  - BACKGROUND: Despite the introduction of the novel cadmium-zinc-telluride (CZT)
      single-photon emission computed tomography (SPECT) in Japan; its diagnostic value
      in clinical practice remains largely unknown. METHODS: The Semiconductor SPECT
      Study group is a multicenter Japanese registry which registered 1000 patients to
      evaluate the diagnostic utility of the CZT camera system (Discovery NM530c; GE
      Healthcare, Haifa, Israel). The patients underwent stress myocardial SPECT and
      coronary angiography within a 3-month interval. A significant stenosis was
      defined as >=75% diameter narrowing based on the American Heart Association
      classification. RESULTS: Technetium (99mTc) radiotracer (555-1110MBq) was used in
      71% and thallium-201 (201Tl) (74-148MBq) in 29%. The scan times with 99mTc
      radiotracer were 5-10min for stress and 3-10min for rest, whereas those with
      201Tl were 5-9min for stress and 8-10min for rest. To detect individual coronary
      stenosis, the respective sensitivities, specificities, and accuracies were 74%,
      85%, and 81% for left anterior descending coronary artery (LAD) stenosis, 76%,
      89%, and 85% for left circumflex stenosis, and 72%, 86%, and 82% for right
      coronary artery stenosis. However, 66% sensitivity and 91% specificity for LAD
      stenosis were observed with 99mTc-radiotracer, whereas 88% sensitivity and 63%
      specificity were found with 201Tl. CONCLUSIONS: The novel CZT SPECT system
      facilitated a short scan time with reduced radiotracer dose, yielding an
      acceptable diagnostic performance for angiographical coronary artery disease,
      although the low sensitivity for LAD detection with 99mTc-radiotracer needs to be
      refined.

PMID- 27021429
TI  - Influence of stroke volume and exercise tolerance on peak oxygen pulse in
      patients with and without beta-adrenergic receptor blockers in patients with
      heart disease.
AB  - BACKGROUND: In a given individual, a consistent relationship exists between
      oxygen uptake (VO2) and heart rate (HR) during exercise. The quotient of VO2 and
      HR (VO2/HR) is called the oxygen pulse (O2 pulse), and its value is dependent on
      stroke volume (SV). However, it is difficult to believe that the O2 pulse would
      indicate the SV when HR has been modified as with the use of beta-adrenergic
      receptor blockers (BB). Until now, the effect of BB on peak O2 pulse has not been
      precisely studied. We tried to clarify the effect of BB on the relationship
      between O2 pulse and SV. METHODS: Of 699 consecutive heart disease subjects who
      performed cardiopulmonary exercise tests (CPX) from 2012 to 2014, we enrolled 430
      subjects who had sinus rhythm and could perform CPX until exhaustion. One hundred
      and fifty-seven subjects were taking BB. SV was evaluated during CPX using
      impedance cardiography, and we compared the peak O2 pulse with peak SV between
      patients without BB (Group A) and with BB (Group B). RESULTS: The HRs at rest and
      peak exercise in Group A were greater than those in Group B (74.4+/-13.0/min vs.
      71.8+/-11.3/min, p<0.01, 134.9+/-21.7/min vs. 124.9+/-23.6/min, p<0.01,
      respectively). The regression line of the peak O2 pulse against the peak SV was
      steeper in Group B than in Group A. When we divided the patients into two groups
      according to the average values of the peak SV and peak VO2, O2 pulse/SV ratio in
      Group B above the average was greater than that in Group A, whereas it was
      similar in the two groups that were below average. CONCLUSION: We found that the
      increase in the O2 pulse was disproportionately greater than the SV that was
      measured by impedance cardiography when a BB was used in patients with preserved
      SV and exercise tolerance.

PMID- 27021430
TI  - Selective electrochemical sensing for arsenite using rGO/Fe3O4 nanocomposites.
AB  - Herein, we report rGO/Fe3O4 nanocomposites (NCs) free from noble metals,
      synthesized by facile one step chemical reduction method, for electrochemical
      detection of arsenite in water by square wave anodic stripping Voltammetry
      (SWASV). The synthesized NCs were characterized for its optical, morphological
      and structural properties. The NCs modified glassy carbon (GCE), NCs/GCE,
      electrodes showed a higher sensitivity (0.281MUA/ppb) and lower LOD (0.12ppb)
      under optimized experimental conditions. The proposed NCs/GCE electrodes show no
      interference towards arsenite species in the presence of common cationic
      interferants, namely, Cu(II), Pb(II), Ni(II), Co(II), Cd(II), Cr(II), Zn(II),
      etc. In addition, the proposed electrode demonstrates a good stability,
      reproducibility and potential practical application in electrochemical detection
      of arsenite.

PMID- 27021431
TI  - Particle-specific toxicity and bioavailability of cerium oxide (CeO2)
      nanoparticles to Arabidopsis thaliana.
AB  - The use of manufactured cerium oxide nanoparticles (CeO2-NPs) in consumer
      products has increased markedly over the past decade, and their release into
      natural ecosystems is unavoidable. This study investigated the phytotoxicity and
      uptake of CeO2-NPs in Arabidopsis thaliana grown in an agar medium. Although low
      concentrations of CeO2-NPs had stimulatory effects on plant growth, at higher
      concentrations, CeO2-NPs reduced growth and had adverse effects on the
      antioxidant systems and photosystem. Importantly, the toxicity resulted from the
      nanoparticles per se, rather than from the dissolved Ce ions. CeO2-NPs were taken
      up and subsequently translocated to shoot tissues, and transmission electron
      microscopy (TEM) showed the presence of a large number of needle-like particle
      aggregations in the intercellular regions and the cytoplasm of leaf cells. The up
      translocation factor to shoots was independent of the concentrations of Ce in the
      roots and the supplied forms of Ce (i.e. CeO2-NPs, CeO2-bulk, and ionic Ce),
      suggesting that endocytosis is likely to be a general mechanism responsible for
      the translocation of these Ce compounds. These findings provide important
      information regarding the toxicity and uptake of CeO2-NPs in plants, which needs
      to be considered in environmental risk assessment for the safe use and disposal
      of CeO2-NPs.

PMID- 27021432
TI  - Determination of gold nanoparticles in environmental water samples by second
      order optical scattering using dithiotreitol-functionalized CdS quantum dots
      after cloud point extraction.
AB  - This work presents a new method for the sensitive and selective determination of
      gold nanoparticles in water samples. The method combines a sample preparation and
      enrichment step based on cloud point extraction with a new detection motif that
      relies on the optical incoherent light scattering of a nano-hybrid assembly that
      is formed by hydrogen bond interactions between gold nanoparticles and
      dithiotreitol-functionalized CdS quantum dots. The experimental parameters
      affecting the extraction and detection of gold nanoparticles were optimized and
      evaluated to the analysis of gold nanoparticles of variable size and surface
      coating. The selectivity of the method against gold ions and other nanoparticle
      species was also evaluated under different conditions reminiscent to those
      usually found in natural water samples. The developed method was applied to the
      analysis of gold nanoparticles in natural waters and wastewater with satisfactory
      results in terms of sensitivity (detection limit at the low pmolL-1 levels),
      recoveries (>80%) and reproducibility (<9%). Compared to other methods employing
      molecular spectrometry for metal nanoparticle analysis, the developed method
      offers improved sensitivity and it is easy-to-operate thus providing an
      additional tool for the monitoring and the assessment of nanoparticles toxicity
      and hazards in the environment.

PMID- 27021433
TI  - Evaluation of third-party reciprocity by squirrel monkeys (Saimiri sciureus) and
      the question of mechanisms.
AB  - Social evaluation during third-party interactions emerges early in human
      ontogeny, and it has been shown in adult capuchin monkeys who witness violations
      of reciprocity in object exchanges: Monkeys were less inclined to accept food
      from humans who refused to reciprocate with another human. A recent study
      reporting similar evidence in marmoset monkeys raised the possibility that such
      evaluations might be based on species' inherent cooperativeness. We tested a
      species not renowned for cooperativeness-squirrel monkeys-using the procedure
      used with marmosets and found a similar result. This finding rules out any
      crucial role for cooperative tendencies in monkeys' responses to unfair
      exchanges. We then tested squirrel monkeys using procedures more similar to those
      used in the original study with capuchins. Squirrel monkeys again accepted food
      less frequently from non-reciprocators, but unlike capuchins, they also strongly
      preferred reciprocators. We conclude that neither squirrel monkeys nor marmoset
      monkeys engaged in emotional bookkeeping of the type that probably underlies
      social evaluation in capuchin monkeys; instead, they employed one or more simple
      behavioral rules. Further comparative studies are required to clarify the
      mechanisms underlying social evaluation processes across species.

PMID- 27021434
TI  - Assessment of toxicity using dehydrogenases activity and mathematical modeling.
AB  - Dehydrogenase activity is frequently used to assess the general condition of
      microorganisms in soil and activated sludge. Many studies have investigated the
      inhibition of dehydrogenase activity by various compounds, including heavy metal
      ions. However, the time after which the measurements are carried out is often
      chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects
      of compounds vary during the reaction and when the maximum of the effect would be
      reached. Hence, the aim of this study was to create simple and useful
      mathematical model describing changes in dehydrogenase activity during exposure
      to substances that inactivate enzymes. Our model is based on the Lagergrens
      pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and
      inactivation and was created to describe short-term changes in dehydrogenase
      activity. The main assumption of our model is that toxic substances cause
      irreversible inactivation of enzyme units. The model is able to predict the
      maximum direct toxic effect (MDTE) and the time to reach this maximum (TMDTE). In
      order to validate our model, we present two examples: inactivation of
      dehydrogenase in microorganisms in soil and activated sludge. The model was
      applied successfully for cadmium and copper ions. Our results indicate that the
      predicted MDTE and TMDTE are more appropriate than EC50 and IC50 for toxicity
      assessments, except for long exposure times. 

PMID- 27021435
TI  - A light-responsive organofluid based on reverse worm-like micelles formed from an
      equi-charged, mixed, anionic gemini surfactant with an azobenzene spacer and a
      cationic conventional surfactant.
AB  - An equally-charged mixture of an anionic gemini surfactant, O,O'-bis(sodium 2
      tetradecylcarboxylate)-p-azodiphendiol (G14-azo), and a cationic surfactant,
      cetyltrimethylammonium bromide (CTAB), was dissolved in cyclohexane to form
      reverse worm-like micelles. Samples with different surfactant concentrations and
      amounts of added water were studied using rheological measurements. The amount of
      water, represented as the molar ratio of water to total surfactants W0, was c. 13
      (at its minimum) in these equally charged systems of G14-azo (200 mmol L(
      1))/CTAB. The low shear viscosity etaL of this system reached 4370 Pa s at W0 =
      13 and the dynamic rheological result showed typical surfactant gel behaviour.
      Under UV-light irradiation, the transparent sample (G14-azo (300 mmol L(-1))/CTAB
      (600 mmol L(-1))) at W0 = 40 became turbid, during which etaL was rapidly reduced
      from the original 285 Pa s to 0.3 Pa s, indicating a transition of aggregate
      morphology from reverse worms into simple reverse micelles. Then the sample was
      returned to its original homogeneous state with c. 290 Pa s viscosity under
      visible light irradiation. However, this transition cannot be well achieved at
      low W0 due to the interior cores being too small. This limit has been attributed
      to both the Gemini type of surfactant molecule and to the inverted structure of
      aggregates.

PMID- 27021437
TI  - Emergency Department Management of Heart Failure and COPD: A National Survey of
      Attitudes and Practice.
AB  - OBJECTIVES: The Ottawa Heart Failure Risk Scale (OHFRS) and the Ottawa COPD Risk
      Scale (OCRS) were developed in order to estimate medical risk and to help guide
      disposition decisions for patients presenting to the ED with acute exacerbations
      of heart failure (HF) and COPD. We sought to determine physician attitudes
      towards these two new risk scales and to identify potential barriers to their ED
      implementation. METHODS: Two self-administered online surveys were distributed to
      the Canadian Association of Emergency Physicians. The surveys each consisted of
      16 questions relating to the OHFRS and OCRS. The primary outcome measures were
      the overall physician rating of the two risk scales. Secondary outcome measures
      assessed the likelihood of risk scale implementation into Canadian EDs, as well
      as the perceived barriers to such implementation. Descriptive statistics were
      used. RESULTS: For the OHFRS survey, we received responses from 195 emergency
      physicians (35.7%). Overall, 74.4% approved of the risk scale based on a Likert
      rating of 4 or 5 and 66.7% believed that the risk scale would be implemented at
      their hospital. For the OCRS survey, we received responses from 208 emergency
      physicians (38.1%). Overall, 76.9% approved of the risk scale based on a Likert
      rating of 4 or 5 and 70.2% believed that the risk scale would be implemented at
      their hospital. CONCLUSIONS: Canadian emergency physicians are very supportive of
      the new OHFRS and OCRS. We believe these risk scales will assist physicians with
      making safe and efficient disposition decisions and improve outcomes for patients
      suffering from HF and COPD.

PMID- 27021436
TI  - Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in
      ovarian cancer cells through targeting APAF1.
AB  - Advanced ovarian cancer usually spreads to the visceral adipose tissue of the
      omentum. However, the omental stromal cell-derived molecular determinants that
      modulate ovarian cancer growth have not been characterized. Here, using next
      generation sequencing technology, we identify significantly higher levels of
      microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer
      associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian
      cancer cells. Functional studies reveal that miR21 is transferred from CAAs or
      CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and
      confers chemoresistance by binding to its direct novel target, APAF1. These data
      suggest that the malignant phenotype of metastatic ovarian cancer cells can be
      altered by miR21 delivered by exosomes derived from neighbouring stromal cells in
      the omental tumour microenvironment, and that inhibiting the transfer of stromal
      derived miR21 is an alternative modality in the treatment of metastatic and
      recurrent ovarian cancer. 

PMID- 27021438
TI  - Predictive value of the RIFLE urine output criteria on contrast-induced
      nephropathy in critically ill patients.
AB  - BACKGROUND: To investigate the predictive value of decreased urine output based
      on the Risk of renal dysfunction, Injury to the kidney, Failure of kidney
      function, Loss of kidney function and End-stage renal disease (RIFLE)
      classification on contrast- induced acute kidney injury (CA-AKI) in intensive
      care (ICU) patients. METHODS: All patients who received contrast media (CM)
      injection for CT scan or coronary angiography during a 3-year period in a 24 bed
      medico-surgical ICU were reviewed. RESULTS: Daily serum creatinine concentrations
      and diuresis were measured for 3 days after CM injection. We identified 23 cases
      of CA-AKI in the 149 patients included (15.4 %). Patients who developed CA-AKI
      were more likely to require renal replacement therapy and had higher ICU
      mortality rates. At least one RIFLE urine output criteria was observed in 45
      patients (30.2 %) and 14 of these 45 patients (31.1 %) developed CA-AKI based on
      creatinine concentrations. In 30 % of these cases, urine output decreased or
      didn't change after the increase in creatinine concentrations. The RIFLE urine
      output criteria had low sensitivity (39.1 %) and specificity (67.9 %) for
      prediction of CA-AKI, a low positive predictive value of 50 % and a negative
      predictive value of 87.2 %. The maximal dose of vasopressors before CM was the
      only independent predictive factor for CA-AKI. CONCLUSIONS: CA-AKI is a frequent
      pathology observed in ICU patients and is associated with increased need for
      renal replacement therapy and increased mortality. The predictive value of RIFLE
      urine output criteria for the development of CA-AKI based on creatinine
      concentrations was low, which limits its use for assessing the effects of
      therapeutic interventions on the development and progression of AKI.

PMID- 27021439
TI  - Annular Lesions and Catenary Forms in Chronic Central Serous Chorioretinopathy.
AB  - PURPOSE: To describe a series of patients exhibiting annular retinal pigment
      epithelial (RPE) lesions in the context of chronic central serous
      chorioretinopathy. DESIGN: Retrospective comparative case series. METHODS:
      Consecutive patients with chronic central serous chorioretinopathy were
      identified from the clinical practices of 3 retina specialists. A subset of
      patients exhibiting annular RPE lesions on fundus autofluorescence was included
      for chart review and examination of multimodal imaging (study group). Patients
      with alternative etiologies for neurosensory detachment or pigment epitheliopathy
      were excluded. A second consecutive cohort of patients, with acute central serous
      chorioretinopathy, was also examined for the presence of annular lesions
      (comparative group). RESULTS: Sixty-seven patients with chronic central serous
      chorioretinopathy were identified. Fourteen eyes of 12 patients exhibited annular
      lesions (study eyes). Mean visual acuity of study eyes was 20/27 (logMAR 0.13, SD
      0.11). Annular lesions were composed of hyperautofluorescent stellate lesions
      arranged in an open or closed ring with intervening foci of punctate
      hypoautofluorescence. Optical coherence tomography showed RPE hyperplasia at the
      perimeters of annular lesions with loss of ellipsoid reflectivity and preserved
      RPE at the lesion center. Annular lesions were confined to the posterior poles
      and appeared to have developed at the margins of chronic neurosensory detachment.
      Forty-three eyes of 30 patients with acute central serous chorioretinopathy
      comprised the comparative group and none of these eyes exhibited annular lesions.
      CONCLUSIONS: Annular lesions occur in up to a fifth of patients with chronic
      central serous chorioretinopathy but carry a relatively good visual prognosis.
      Curvilinear RPE figures and demarcation lines are seen in various retinal
      conditions but the characteristics of annular lesions described here suggest that
      they are specific to chronic central serous chorioretinopathy.

PMID- 27021441
TI  - Combined Electrical and Optical Characterization of Polydiacetylene.
AB  - Polydiacetylene (PDA) is a conductive polymer that has mechanochromism. When the
      polymer is exposed to mechanical stresses, change in temperature
      (thermochromism), pH (ionochromism), and so forth, the structural perturbation
      can be seen by the change in its color. Although it presents interesting
      electrical and optical properties, the relationship between these signals has
      rarely been investigated. We studied the correlation between the electrical
      conductivity and the absorption spectra of PDA. Upon UV irradiation, PDA
      absorption spectra presented a blue shift, which coincided with the decrease in
      the electrical conductivity. 

PMID- 27021442
TI  - Simply the best.

PMID- 27021443
TI  - Linking orthodontic treatment and caries management for high-risk adolescents.

PMID- 27021440
TI  - Investigating the Microstructural Correlation of White Matter in Autism Spectrum
      Disorder.
AB  - White matter microstructure forms a complex and dynamical system that is critical
      for efficient and synchronized brain function. Neuroimaging findings in children
      with autism spectrum disorder (ASD) suggest this condition is associated with
      altered white matter microstructure, which may lead to atypical macroscale brain
      connectivity. In this study, we used diffusion tensor imaging measures to examine
      the extent that white matter tracts are interrelated within ASD and typical
      development. We assessed the strength of inter-regional white matter correlations
      between typically developing and ASD diagnosed individuals. Using hierarchical
      clustering analysis, clustering patterns of the pairwise white matter
      correlations were constructed and revealed to be different between the two
      groups. Additionally, we explored the use of graph theory analysis to examine the
      characteristics of the patterns formed by inter-regional white matter
      correlations and compared these properties between ASD and typical development.
      We demonstrate that the ASD sample has significantly less coherence in white
      matter microstructure across the brain compared to that in the typical
      development sample. The ASD group also presented altered topological
      characteristics, which may implicate less efficient brain networking in ASD.
      These findings highlight the potential of graph theory based network
      characteristics to describe the underlying networks as measured by diffusion
      magnetic resonance imaging and furthermore indicates that ASD may be associated
      with altered brain network characteristics. Our findings are consistent with
      those of a growing number of studies and hypotheses that have suggested disrupted
      brain connectivity in ASD.

PMID- 27021444
TI  - Bone and cartilage changes after injection of botulinum toxin.

PMID- 27021445
TI  - Authors' response.

PMID- 27021446
TI  - Corticotomy-assisted rapid maxillary expansion.

PMID- 27021447
TI  - One hundred years of orthodontic history.

PMID- 27021448
TI  - Would you do it again?

PMID- 27021449
TI  - Surgery first in orthognathic surgery: A systematic review of the literature.
AB  - INTRODUCTION: Compared to the conventional approach to orthognathic surgery,
      "surgery first" protocols could be advantageous in terms of shortened treatment
      times and immediate esthetic improvement. However, consensus regarding patient
      selection, technical protocol, and stability is still lacking. METHODS: A
      systematic review of the scientific literature on surgery-first treatment
      (January 2000 to January 2015) was performed. The PubMED and Cochrane Library
      databases were accessed. Patient selection criteria, specific surgical
      orthodontic protocol, treatment duration, patient and orthodontist satisfaction,
      and stability of results were compared with a similar population treated
      conventionally. RESULTS: The search yielded 179 publications. The application of
      strict selection criteria gave the final group of 11 articles. In total, 295
      patients were managed with a surgery-first approach. A Class III malocclusion was
      the most prevalent underlying malocclusion (84.7%). Total treatment duration was
      shorter in surgery-first patients than in those treated conventionally. There was
      substantial heterogeneity among articles and high reporting bias regarding the
      inclusion and exclusion criteria, the orthodontic and surgical protocols, and the
      stability of results. A meta-analysis of combined data was not possible.
      CONCLUSIONS: The surgery-first approach is a new treatment paradigm for the
      management of dentomaxillofacial deformity. Studies have reported satisfactory
      outcomes and high acceptance. However, the results should be interpreted with
      caution because of the wide varieties of study designs and outcome variables,
      reporting biases, and lack of prospective long-term follow-ups.

PMID- 27021450
TI  - Periodontal status after surgical-orthodontic treatment of labially impacted
      canines with different surgical techniques: A systematic review.
AB  - INTRODUCTION: Good periodontal status is essential for a successful treatment
      outcome of impacted maxillary canines. Whereas the surgical technique used for
      tooth uncovering has been shown not to affect the final periodontal status of
      palatally impacted canines, its effect on labially impacted canines is still
      unclear. METHODS: Searches of electronic databases through January 2015 and
      reference lists of relevant publications were used to identify studies evaluating
      the periodontal status of labially impacted canines after combined surgical
      orthodontic treatment. Two reviewers independently screened the articles,
      extracted data, and ascertained the quality of the studies. RESULTS: Ninety-one
      studies were identified; 3 were included in the review. No included study
      examined the periodontal outcome of the closed eruption technique. Excisional
      uncovering was reported to have a detrimental effect on the periodontium
      (bleeding of the gingival margin, 29% vs 7% in the control group; gingival
      recession, -0.5 mm [SD, 1.0] vs -1.5 mm [SD, 0.8] in the control group; and width
      of keratinized gingiva, 2.6 mm [SD, 1.4] vs 4.1 mm [SD, 1.5] in the control
      group). Impacted canines uncovered with an apically positioned flap had
      periodontal outcomes comparable with those of untreated teeth. CONCLUSIONS: The
      current literature is insufficient to determine which surgical procedure is
      better for periodontal health for uncovering labially impacted canines.

PMID- 27021451
TI  - Evaluation of corticotomy-facilitated orthodontics and piezocision in rapid
      canine retraction.
AB  - INTRODUCTION: The purpose of this study was to evaluate the efficiency of
      corticotomy-facilitated orthodontics and piezocision in rapid canine retraction.
      METHODS: The sample consisted of 20 patients (15-25 years old) with Class II
      Division 1 malocclusions. The suggested treatment plan was extraction of the
      maxillary first premolars with subsequent canine retraction. The sample was
      divided into 2 equal groups. In the first group, 1 side of the maxillary arch was
      randomly chosen for treatment with corticotomy, and in the second group,
      piezocision treatment was used. The contralateral sides of both groups served as
      the controls. Cuts and perforations were performed with a piezotome, and canine
      retraction was initiated bilaterally in both groups with closed-coil nickel
      titanium springs that applied 150 g of force on each side. The following
      variables were examined over a 3-month follow-up period: rate of canine crown
      tip, molar anchorage loss, canine rotation, canine inclination, canine root
      resorption, plaque index, gingival index, probing depth, attachment level, and
      gingival recession. The rate of canine crown tip was assessed every 2 weeks after
      the start of canine retraction at 6 time points. RESULTS: The rates of canine
      crown tip were greater in the experimental sides than in the control sides in
      both groups. Corticotomies produced greater rates of canine movement than did
      piezocision at 4 time points. Canine root resorption was greater in the control
      sides. The remaining studied variables exhibited no differences between the
      control and the experimental sides. CONCLUSIONS: Corticotomy-facilitated
      orthodontics and piezocision are efficient treatment modalities for accelerating
      canine retraction.

PMID- 27021452
TI  - Posttreatment evaluation of maxillary canine positions in 15-year-old subjects.
AB  - INTRODUCTION: Esthetic improvement is a primary reason that people seek
      orthodontic treatment. The maxillary canine is considered by many to have great
      importance for both function and esthetics. Limited information is available
      about the position of the maxillary canine in relation to skeletal landmarks and
      whether the position can influence esthetic perceptions. The purposes of this
      study were to evaluate the normal maxillary canine position in relation to
      skeletal landmarks, to determine posttreatment 3-dimensional maxillary canine
      position with cone-beam computed tomography images, and to see whether maxillary
      canine position influences esthetic perceptions. METHODS: The Bolton standard
      template was used as the control sample, and the maxillary canine position was
      determined by implementing a Cartesian coordinate system. The right and left
      maxillary canines of 96 treated patients (48 boys, 48 girls; 15 years old) were
      analyzed by digitization of the cone-beam computed tomography volumes. The
      subjects' posttreatment smile photographs were ranked and quantified by 9
      orthodontic residents who completed a Q-sort. Correlations were determined
      between canine positions and esthetic outcomes. RESULTS: The only difference
      between the right and left canine positions was the anteroposterior position of
      the root apex. Statistically significant sex differences were found for the
      superoinferior position of the right and left canine cusp tips, the mediolateral
      right and left canine root apices, and the mediolateral left canine cusp tips. No
      correlation was determined between the maxillary canine position and the esthetic
      perception. CONCLUSIONS: The maxillary canine position in relation to skeletal
      landmarks was determined and does not appear to significantly impact the esthetic
      perception, according to this study.

PMID- 27021453
TI  - Orthodontic pain trajectories in adolescents: Between-subject and within-subject
      variability in pain perception.
AB  - INTRODUCTION: The objective of this study was to assess the effects of age, sex,
      and the age-sex interaction on mean pain trajectories and individual variations
      in the pain experienced by adolescents after orthodontic separator placement.
      METHODS: We included 115 subjects (mean age, 14.99 years; SD, +/-1.90 years; 56
      boys, 48.7%; 59 girls, 51.3%) in this study. Orthodontic separators were placed
      in the mesial and distal contact points of the maxillary and mandibular first
      molars. A 100-mm visual analog scale was used for pain assessment at 11
      prespecified times: 1 hour and 2, 4, 12, 24, 36, 48, 72, 96, 120, and 144 hours.
      A mixed-effects location scale model was used for the data analysis to directly
      model between-subject and within-subject variabilities in pain in addition to the
      usual modeling of mean pain as a function of age, sex, and time. RESULTS: Mean
      initial pain after 1 hour of separator placement for the 12- to 15-year-old male
      group was 13.52 mm on the visual analog scale, which initially increased rapidly
      (linear estimate, 9.16; P = 0.000; 95% confidence interval [CI], -8.65 to 9.67)
      but decelerated with time (quadratic estimate, -0.95; P = 0.000; 95% CI, -1.0 to 
      0.90), suggesting an inverted U-shaped mean pain trajectory. Age, sex, and age
      sex interaction effects did not significantly influence initial pain. Compared
      with the 12- to 15-year-old male group, the 15- to 18-year-old female group
      reported the steepest rise in pain (estimate, 8.55; P = 0.00; 95% CI, 7.40 to
      9.70) and, as a result, experienced the most overall pain. The 12- to 15-year-old
      male group reported minimum between-subjects variations (SD, +/-4.6 mm) as well
      as within-subjects variations (SD, +/-5.5 mm). The between-subjects variations
      were highest for the 12- to 15-year-old female group (SD, +/-9.8 mm), whereas the
      within-subjects variations were highest for the 15- to 18-year-old female group
      (SD, +/-10.1 mm). CONCLUSIONS: The 12- to 15-year-old boys reported the lowest
      mean average pain intensity and a minimum subjective variation in between-subject
      and within-subject variances. The 15- to 18-year-old girls experienced maximum
      mean pain intensity and the highest daily fluctuations in pain intensity. The 12-
      to 15-year-old girls were the most different from one another in their overall
      pain experience.

PMID- 27021454
TI  - Facial surface morphology predicts variation in internal skeletal shape.
AB  - INTRODUCTION: The regular collection of 3-dimensional (3D) imaging data is
      critical to the development and implementation of accurate predictive models of
      facial skeletal growth. However, repeated exposure to x-ray-based modalities such
      as cone-beam computed tomography has unknown risks that outweigh many potential
      benefits, especially in pediatric patients. One solution is to make inferences
      about the facial skeleton from external 3D surface morphology captured using safe
      nonionizing imaging modalities alone. However, the degree to which external 3D
      facial shape is an accurate proxy of skeletal morphology has not been previously
      quantified. As a first step in validating this approach, we tested the hypothesis
      that population-level variation in the 3D shape of the face and skeleton
      significantly covaries. METHODS: We retrospectively analyzed 3D surface and
      skeletal morphology from a previously collected cross-sectional cone-beam
      computed tomography database of nonsurgical orthodontics patients and used
      geometric morphometrics and multivariate statistics to test the hypothesis that
      shape variation in external face and internal skeleton covaries. RESULTS:
      External facial morphology is highly predictive of variation in internal skeletal
      shape ([Rv] = 0.56, P <0.0001; partial least squares [PLS] 1-13 = 98.7%
      covariance, P <0.001) and asymmetry (Rv = 0.34, P <0.0001; PLS 1-5 = 90.2%
      covariance, P <0.001), whereas age-related (r(2) = 0.84, P <0.001) and size
      related (r(2) = 0.67, P <0.001) shape variation was also highly correlated.
      CONCLUSIONS: Surface morphology is a reliable source of proxy data for the
      characterization of skeletal shape variation and thus is particularly valuable in
      research designs where reducing potential long-term risks associated with
      radiologic imaging methods is warranted. We propose that longitudinal surface
      morphology from early childhood through late adolescence can be a valuable source
      of data that will facilitate the development of personalized craniodental and
      treatment plans and reduce exposure levels to as low as reasonably achievable.

PMID- 27021455
TI  - Utility of panoramic radiography for identification of the pubertal growth
      period.
AB  - INTRODUCTION: Our aim in this study was to investigate the association between
      dental mineralization stages and the periods of the pubertal growth spurt (PGS).
      METHODS: The sample included panoramic and hand-wrist radiographs from 491
      subjects (222 boys, 269 girls) aged 7 to 17 years. Dental development was rated,
      and skeletal maturation was evaluated. The relevant associations were
      investigated by analysis of ordinal multinomial logistic regression. RESULTS: The
      second molar (odds ratio [OR] = 4.34) and the first premolar (OR = 2.45) were the
      best growth predictors for girls. For boys, the second molar (OR = 6.80), second
      premolar (OR = 2.41), and canine (OR = 3.21) proved to be the best predictors.
      Stages D and E of the second molar for girls, and stages E and F for boys,
      corresponded to the onset of the accelerated growth spurt. Stage F of the second
      molar for girls and stage G for boys corresponded to the peak of the PGS. At the
      end of the PGS, most teeth had already attained apical closure. In girls,
      however, most second molars were found at stage G. CONCLUSIONS: An association
      exists between the dental mineralization stages and the periods of the PGS,
      especially for second molars. Panoramic radiographs can be used as the first
      diagnostic tool to estimate the pubertal growth period.

PMID- 27021456
TI  - Racial disparities in orthodontic service use for Medicaid-enrolled children: An
      evaluation of the Washington Medicaid program.
AB  - INTRODUCTION: We assessed the relationship between race and orthodontic service
      use for Medicaid-enrolled children. METHODS: This cross-sectional study focused
      on 570,364 Medicaid-enrolled children in Washington state, ages 6 to 19 years.
      The main predictor variable was self-reported race (white vs nonwhite). The
      outcome variable was orthodontic service use, defined as children who were
      preauthorized for orthodontic treatment by Medicaid in 2012 and subsequently
      received orthodontic records and initiated treatment. Logistic regression models
      were used to test the hypothesis that nonwhites are less likely to use
      orthodontic care than are whites. RESULTS: A total of 8223 children were approved
      by Medicaid for orthodontic treatment, and 7313 received records and began
      treatment. Nonwhites were significantly more likely to use orthodontic care than
      were whites (odds ratio [OR] = 1.18; 95% confidence interval [CI] = 1.02, 1.36; P
      = 0.031). Hispanic nonwhite children were more likely to use orthodontic care
      than were non-Hispanic white children (OR = 1.42; 95% CI = 1.18, 1.70; P <0.001).
      CONCLUSIONS: In 2012, nonwhite children in the Washington Medicaid program were
      significantly more likely to use orthodontic care than were white children. The
      Washington Medicaid program demonstrates a potential model for addressing racial
      disparities in orthodontic service use. Future research should identify
      mechanisms underlying these findings and continue to monitor orthodontic service
      use for minority children in Medicaid.

PMID- 27021457
TI  - BoneCeramic graft regenerates alveolar defects but slows orthodontic tooth
      movement with less root resorption.
AB  - INTRODUCTION: BoneCeramic (Straumann, Basel, Switzerland) can regenerate bone in
      alveolar defects after tooth extraction, but it is unknown whether it is feasible
      to move a tooth through BoneCeramic grafting sites. The objective of this study
      was to investigate 3-dimensional real-time root resorption and bone responses in
      grafted sites during orthodontic tooth movement. METHODS: Sixty 5-week-old rats
      were randomly assigned to 3 groups to receive BoneCeramic, natural bovine
      cancellous bone particles (Bio-Oss; Geistlich Pharma, Wolhusen, Switzerland), or
      no graft, after the extraction of the maxillary left first molar. After 4 weeks,
      the maxillary left second molar was moved into the extraction site for 28 days.
      Dynamic bone microstructures and root resorption were evaluated using in-vivo
      microcomputed tomography. Stress distribution and corresponding tissue responses
      were examined by the finite element method and histology. Mixed model analysis of
      variance was performed to compare the differences among time points with
      Bonferroni post-hoc tests at the significance level of P <0.05. RESULTS: The
      BoneCeramic group had the least amount of tooth movement and root resorption
      volumes and craters, and the highest bone volume fraction, trabecular number, and
      mean trabecular thickness, followed by the Bio-Oss and the control groups. The
      highest stress accumulated in the cervical region of the mesial roots.
      CONCLUSIONS: BoneCeramic has better osteoconductive potential and induces less
      root resorption compared with Bio-Oss grafting and naturally recovered extraction
      sites.

PMID- 27021458
TI  - Comparison and reproducibility of 2 regions of reference for maxillary regional
      registration with cone-beam computed tomography.
AB  - INTRODUCTION: The aims of this study were to evaluate the differences between 2
      regions of maxillary voxel-based registration and to test the reproducibility of
      the registration. METHODS: Three-dimensional models were built for before
      treatment (T1) and after-treatment (T2) based on cone-beam computed tomography
      images from 16 growing subjects. Landmarks were labeled in all T2 models of the
      maxilla, and voxel-based registrations were performed independently by 2
      observers at 2 times using 2 reference regions. The first region, the maxillary
      region, included the maxillary bone clipped inferiorly at the dentoalveolar
      processes, superiorly at the plane passing through the right and left orbitale
      points, laterally at the zygomatic processes through the orbitale point, and
      posteriorly at a plane passing through the distal surface of the second molars.
      In the second region, the palate and infrazygomatic region had different
      posterior and anterior limits (at the plane passing through the distal aspects of
      the first molars and the canines, respectively). The differences between the
      registration regions were measured by comparing the distances between
      corresponding landmarks in the T2 registered models and comparing the
      corresponding x, y, and z coordinates from corresponding landmarks. Statistical
      analysis of the differences between the T2 surface models was performed by
      evaluating the means and standard deviations of the distances between landmarks
      and by testing the agreement between coordinates from corresponding landmarks
      (intraclass correlation coefficient and Bland-Altman method). RESULTS: The means
      of the differences between landmarks from the palate and infrazygomatic region to
      the maxillary region 3-dimensional surface models at T2 for all regions of
      reference, times of registrations, and observer combinations were smaller than
      0.5 mm. The intraclass correlation coefficient and the Bland-Altman plots
      indicated adequate concordance. CONCLUSIONS: The 2 regions of regional maxillary
      registration showed similar results and adequate intraobserver and interobserver
      reproducibility values.

PMID- 27021459
TI  - Objective vs subjective analyses of arch form and preformed archwire selection.
AB  - INTRODUCTION: Maintaining a patient's original arch form increases treatment
      stability. In this study, we assessed the agreement between subjective analyses
      of arch form and archwire selection by orthodontists and an objective method with
      Cast Analyzer Iranian X software (Khallaghane Mehr, Tehran, Iran). METHODS:
      Thirty-six casts with normal occlusion were scanned with a laser. The software
      generated the best-fit curve using a fourth-degree polynomial equation to the
      clinical bracket points on the casts; then it selected the best preformed nickel
      titanium archwire based on the root mean square calculation either objectively or
      semiobjectively. Three orthodontists selected the best-fit curve and archwire
      subjectively using the casts. To assess intraexaminer reliability, the same
      orthodontists reevaluated 10 casts after 2 weeks. To assess interexaminer
      reliability, the 3 orthodontists performed the analyses with the software and on
      the casts. Agreements were evaluated with the intraclass correlation coefficient
      and Dahlberg's formula. RESULTS: The semiobjective method (visual selection of
      wire by orthodontists using the software) yielded the best results. The
      differences were clinically negligible between the objective (fully automated)
      and semiobjective methods (1.30 vs 1.36 mm). CONCLUSIONS: The objective method
      improved wire adaptation to the clinical bracket points. Agreement among
      orthodontists regarding wire selection will improve significantly when they are
      trained to use the software.

PMID- 27021460
TI  - Diagnosis and conservative treatment of skeletal Class III malocclusion with
      anterior crossbite and asymmetric maxillary crowding.
AB  - A man, aged 28 years 9 months, came for an orthodontic consultation for a
      skeletal Class III malocclusion (ANB angle, -3 degrees ) with a modest asymmetric
      Class II and Class III molar relationship, complicated by an anterior crossbite,
      a deepbite, and 12 mm of asymmetric maxillary crowding. Despite the severity of
      the malocclusion (Discrepancy Index, 37), the patient desired noninvasive
      camouflage treatment. The 3-Ring diagnosis showed that treatment without
      extractions or orthognathic surgery was a viable approach. Arch length analysis
      indicated that differential interproximal enamel reduction could resolve the
      crowding and midline discrepancy, but a miniscrew in the infrazygomatic crest was
      needed to retract the right buccal segment. The patient accepted the complex,
      staged treatment plan with the understanding that it would require about 3.5
      years. Fixed appliance treatment with passive self-ligating brackets, early light
      short elastics, bite turbos, interproximal enamel reduction, and infrazygomatic
      crest retraction opened the vertical dimension of the occlusion, improved the ANB
      angle by 2 degrees , and achieved excellent alignment, as evidenced by a Cast
      Radiograph Evaluation score of 28 and a Pink and White dental esthetic score of
      3. 

PMID- 27021461
TI  - User acceptance of a touchless sterile system to control virtual orthodontic
      study models.
AB  - INTRODUCTION: In this article, we present an evaluation of user acceptance of our
      innovative hand-gesture-based touchless sterile system for interaction with and
      control of a set of 3-dimensional digitized orthodontic study models using the
      Kinect motion-capture sensor (Microsoft, Redmond, Wash). METHODS: The system was
      tested on a cohort of 201 participants. Using our validated questionnaire, the
      participants evaluated 7 hand-gesture-based commands that allowed the user to
      adjust the model in size, position, and aspect and to switch the image on the
      screen to view the maxillary arch, the mandibular arch, or models in occlusion.
      Participants' responses were assessed using Rasch analysis so that their
      perceptions of the usefulness of the hand gestures for the commands could be
      directly referenced against their acceptance of the gestures. Their perceptions
      of the potential value of this system for cross-infection control were also
      evaluated. RESULTS: Most participants endorsed these commands as accurate. Our
      designated hand gestures for these commands were generally accepted. We also
      found a positive and significant correlation between our participants' level of
      awareness of cross infection and their endorsement to use this system in clinical
      practice. CONCLUSIONS: This study supports the adoption of this promising
      development for a sterile touch-free patient record-management system.

PMID- 27021462
TI  - Leaving something behind.

PMID- 27021463
TI  - Multiple linear regression analysis.

PMID- 27021464
TI  - Observation of momentum-resolved charge fluctuations proximate to the charge
      order phase using resonant inelastic x-ray scattering.
AB  - In strongly correlated electron systems, enhanced fluctuations in the proximity
      of the ordered states of electronic degrees of freedom often induce anomalous
      electronic properties such as unconventional superconductivity. While spin
      fluctuations in the energy-momentum space have been studied widely using
      inelastic neutron scattering, other degrees of freedom, i.e., charge and orbital,
      have hardly been explored thus far. Here, we use resonant inelastic x-ray
      scattering to observe charge fluctuations proximate to the charge-order phase in
      transition metal oxides. In the two-leg ladder of Sr(14-x)Ca(x)Cu24O41, charge
      fluctuations are enhanced at the propagation vector of the charge order (qCO)
      when the order is melted by raising temperature or by doping holes. In contrast,
      charge fluctuations are observed not only at qCO but also at other momenta in a
      geometrically frustrated triangular bilayer lattice of LuFe2O4. The observed
      charge fluctuations have a high energy (~1 eV), suggesting that the Coulomb
      repulsion between electrons plays an important role in the formation of the
      charge order.

PMID- 27021465
TI  - Improving drug retention in liposomes by aging with the aid of glucose.
AB  - This paper describes a novel method to improve drug retention in liposomes for
      the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded
      in the aqueous phase of liposomes and the effects of aging conditions and drug
      loading levels on drug retention were investigated using an in vitro bio-relevant
      drug release test established in this study. The status of intra-liposomal drug
      was investigated using differential scanning calorimetry (DSC) and cryo
      transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous
      tolerance of the formulations were simultaneously studied in rabbits following
      one-hour intravenous infusion via the ear vein. The presence of glucose during
      aging was found to be crucial to accelerate drug precipitation and to stabilize
      the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a
      prerequisite. Although no drug crystals were detected, DSC showed a lower phase
      transition peak in the glucose-assisted aged ASL-liposomes, indicating
      interaction of phospholipids with the sugar. Cryo-TEM revealed more 'coffee bean'
      like drug precipitate in the ASL-liposomes aged in the glucose solution. In
      rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh
      liposomes, with no venous irritation observed. Inducing and stabilizing drug
      precipitation in the liposome cores by aging in the presence of sugar provided an
      easy approach to improve drug retention in liposomes. The study also highlighted
      the importance of bio-relevance of in vitro release methods to predict in vivo
      drug release. 

PMID- 27021466
TI  - The self-assemble of natural cyclodextrins in aqueous solutions: Application of
      miniature permeation studies for critical aggregation concentration (cac)
      determinations.
AB  - Permeation techniques can be applied to determine the critical aggregation
      concentration (cac) of natural cyclodextrins (CDs) in aqueous solutions although
      the method is both laborious and time consuming. In the present study, the
      permeation technique was modified and the influence of osmotic pressure, sampling
      time, CD concentration and molecular weight-cut off (MWCO) of the membrane were
      investigated in two different permeation units, that is Franz diffusion cells and
      Slide-A-LyzerTM MINI Dialysis. While both the osmotic pressure and CD
      concentration affect the steady state flux in both permeation units, effects of
      sampling time and the MWCO of the mounted membrane were only observed in the
      Franz diffusion cells. The osmotic effect was negligible in the Slide-A-LyzerTM
      MINI Dialysis units. The modified permeation technique using Slide-A-LyzerTM MINI
      Dialysis units was then used to determine the cac of natural CDs in water. The
      cac of alphaCD, betaCD and gammaCD was 1.19+/-0.17, 0.69+/-0.05 and 0.93+/-0.04%
      (w/v), respectively. The results indicated that the cac values depended on their
      intrinsic solubility. Moreover, the cac value of gammaCD in aqueous
      hydrocortisone/gammaCD inclusion complex solution was identical to the gammaCD
      cac value determined in pure water. 

PMID- 27021467
TI  - PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-epsilon
      caprolactone nanoparticles.
AB  - In this work lyophilized poly-epsilon-caprolactone nanoparticles (NPs) loaded
      with atorvastatin calcium (AC) were developed in an attempt to improve the in
      vivo performance of AC following oral administration. The individual and combined
      effects of several formulation variables were previously investigated using step
      wise full factorial designs in order to produce optimized AC-NPs with
      predetermined characteristics including particle size, drug loading capacity,
      drug release profile and physical stability. Four optimized formulations were
      further subjected in this work to lyophilization to promote their long-term
      physical stability and were fully characterized. The pharmacodynamics
      (PD)/pharmacokinetics (PK) properties of two optimized freeze-dried AC-NPs
      formulations showing acceptable long-term stability were determined and compared
      to a marketed AC immediate release tablet (Lipitor((r))) in albino rats. PD
      results revealed that the two tested formulations were equally effective in
      reducing low density lipoproteins (LDL) and triglycerides (TG) levels when given
      in reduced doses compared to Lipitor((r)) and showed no adverse effects. PK
      results, on the other hand, revealed that the two freeze-dried AC-NPs
      formulations were of significantly lower bioavailability compared to
      Lipitor((r)). Taken together the PD and PK results demonstrate that the improved
      efficacy obtained at reduced doses from the freeze-dried AC-NPs could be due to
      increased concentration of AC in the liver rather than in the plasma. 

PMID- 27021468
TI  - Socioeconomic and demographic drivers of red and processed meat consumption:
      implications for health and environmental sustainability.
AB  - Red and processed meat (RPM) intake varies widely globally. In some high-income
      countries (HIC) the last decade has witnessed an overall decline or stabilisation
      in the consumption of RPM, in contrast to emerging economies where its
      consumption continues to increase with rising income and rapid urbanisation. The
      production and consumption of RPM have become major concerns regarding the
      environmental impacts of livestock in particular, but also because of
      associations between high RPM consumption and diet-related non-communicable
      disease. Therefore, it is important to identify socioeconomic and demographic
      drivers of the consumption of RPM. This paper explores how consumption of RPM
      differs with age, gender, socioeconomic status and in different global contexts.
      There are some key socioeconomic and demographic patterns in RPM consumption. Men
      tend to consume RPM more often and in higher quantities, and there is evidence of
      a social gradient in HIC, with lower socioeconomic groups consuming RPM more
      often and in larger quantities. Patterns for consumption with age are less clear
      cut. It is apparent that consumers in HIC are still consuming high levels of RPM,
      although the downward shifts in some socioeconomic and demographic groups is
      encouraging and suggests that strategies could be developed to engage those
      consumers identified as high RPM consumers. In low- and middle-income countries,
      RPM consumption is rising, especially in China and Brazil, and in urban areas.
      Ways of encouraging populations to maintain their traditional healthy eating
      patterns need to be found in low- and middle-income countries, which will have
      health, environmental and economic co-benefits.

PMID- 27021469
TI  - Slow pathway modification in patients presenting with only two consecutive AV
      nodal echo beats.
AB  - BACKGROUND: Slow pathway modification (SPM) is the therapy of choice for AV-nodal
      reentry tachycardia (AVNRT). When AVNRT is not inducible, empirical ablation can
      be considered, however, the outcome in patients with two AV nodal echo beats
      (AVNEBs) is unknown. METHODS: Out of a population of 3003 patients who underwent
      slow pathway modification at our institution between 1993 and 2013, we
      retrospectively included 32 patients with a history of symptomatic tachycardia,
      lack of paroxysmal supraventricular tachycardia (pSVT) inducibility but
      occurrence of two AVNEBs. RESULTS: pSVT documentation by electrocardiography
      (ECG) was present in 20 patients. The procedural endpoint was inducibility of
      less than two AVNEBs. This was reached in 31 (97%) patients. Long-term success
      was assessed by a telephone questionnaire (follow-up time 63+/-9 months). A total
      94% of the patients benefited from the procedure (59% freedom from symptoms; 34%
      improvement in symptoms). Among those patients in whom ECG documentation was not
      present, 100% benefited (58% freedom from symptoms, 42% improvement). CONCLUSION:
      This is the first collective analysis of a group of patients presenting with
      symptoms of pSVT and inducibility of only two AVNEBs. Procedural success and
      clinical long-term follow-up were in the range of the reported success rates of
      slow pathway modification of inducible AVNRT, independent of whether ECG
      documentation was present. Thus, SPM is a safe and effective therapy in patients
      with two AVNEBs.

PMID- 27021470
TI  - Adequate time in therapeutic INR range using triple antithrombotic therapy is not
      associated with long-term cardiovascular events and major bleeding complications
      after drug-eluting stent implantation.
AB  - BACKGROUND: Triple antithrombotic therapy increases the risk of bleeding events
      in patients undergoing percutaneous coronary intervention (PCI) compared with
      dual anti-platelet therapy (DAPT). However, whether warfarin control is
      associated with reduced cardiovascular events and major bleeding events in
      patients undergoing PCI with triple antithrombotic therapy is uncertain. METHODS:
      We investigated 1207 consecutive patients who underwent PCI between 2004 and
      2011. Major bleeding complications and major adverse cardiac and cerebrovascular
      events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel
      revascularization, and stroke were compared between groups of patients who
      received either triple antithrombotic therapy or DAPT. RESULTS: Triple
      antithrombotic therapy was administered to 95 (7.9%) patients. The mean
      international normalized ratio of prothrombin time (PT-INR) was 1.8. The target
      PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the
      therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile
      range, 67.4-87.6%). Kaplan-Meier survival curves showed that warfarin therapy was
      not associated with MACCE (p=0.89) and major bleeding (p=0.80). Multivariable Cox
      regression analysis revealed that triple antithrombotic therapy was not an
      independent predictor of MACCE and major bleeding. CONCLUSIONS: Triple
      antithrombotic therapy does not increase the occurrence of MACCE and major
      bleeding complications, if the warfarin dose is tightly controlled with a lower
      INR.

PMID- 27021471
TI  - A finite element model to investigate the effect of ulnar variance on distal
      radioulnar joint mechanics.
AB  - Ulnocarpal impaction syndrome involves excessive loading of the ulnocarpal joint.
      Ulnar shortening osteotomies are an effective way to reduce ulnocarpal loading
      but alter contact mechanics at the distal radioulnar joint (DRUJ). This study
      used a computational model to investigate the relationship between ulnar length
      and DRUJ mechanics. Detailed, finite element models of the radius and ulna bones
      were constructed from magnetic resonance imaging data. The length of the ulna
      bone model was increased and decreased up to 5 mm in 1 mm increments. A
      computational model was used to predict joint contact at the DRUJ for each ulnar
      length. Lengthening the ulna caused a slight decrease in DRUJ contact pressure,
      with a more substantial decrease in contact area. Shortening the ulna caused a
      substantial increase in contact area, with a smaller increase in DRUJ contact
      pressure. The location of contact on the radial sigmoid notch changed with 2 mm
      lengthening and 3 mm shortening. The results of this study demonstrate the
      sensitivity of DRUJ contact to ulnar length changes, which may explain the DRUJ
      cartilage degeneration that often follows ulnar osteotomies. The joint contact
      model implemented in this study allowed the relationship between ulnar length and
      DRUJ contact to be examined systematically, in a way that is difficult to achieve
      through cadaveric experimentation. The results confirmed published experimental
      data showing an increased DRUJ contact pressure with ulnar shortening. It is
      important that clinicians consider the influence of ulnar osteotomies, not only
      on ulnocarpal loading but also on DRUJ mechanics. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27021472
TI  - Safety and clinical effectiveness of propofol for endoscopic retrograde
      cholangiopancreatography.

PMID- 27021473
TI  - Acute and chronic anemia and short- and long-term outcome of patients with
      peripheral arterial disease and critical limb ischemia.
AB  - BACKGROUND: Evident data about the additive effect of "the fifth cardiovascular
      risk factor" (anemia) and peripheral arterial disease (PAD) focused on morbidity
      and outcome of patients with PAD are currently still missing. METHODS AND
      RESULTS: A total of 41,882 PAD patients were included. Of these, 5566 (13.3%)
      suffered from anemia. Patients with anemia were older (P<0.001), suffered more
      often from chronic kidney disease (P<0.001), coronary artery disease (P<0.001),
      and more severe PAD (P<0.001). However, they received significantly less
      endovascular revascularizations (P<0.001), had higher amputation rates (acute
      anemia: 3.7-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease:
      2.9-fold, P<0.001), higher in-hospital mortality rates (acute anemia: 6.4-fold,
      P<0.001; nutritional, aplastic, and anemia in chronic disease: 4.6-fold;
      P<0.001), had significantly higher in-hospital complications (P<0.001) compared
      to those without anemia. During a follow-up time up to 4years (until Dec. 31st,
      2012, median 775days, 25th-75th percentiles 469-1120days) nutritional, aplastic,
      and anemia in chronic disease and acute anemia were high significant predictors
      of long-term mortality and amputation (each P<0.001). Lengths of hospital stay
      and reimbursement costs were higher (nutritional, aplastic, and anemia in chronic
      disease: 2-fold higher (P<0.001), acute anemia: 3-fold higher (P<0.001)) than in
      patients without anemia. CONCLUSION: This study illustrates from a large,
      comprehensive database the association of acute, nutritional, aplastic, and
      anemia in chronic disease on morbidity, in-hospital treatment and complications,
      short- and long term outcome, and costs of patients with PAD.

PMID- 27021474
TI  - Mutational analysis of COASY in an Italian patient with NBIA.

PMID- 27021475
TI  - Gender gap matters in maternal mortality in low and lower-middle-income
      countries: A study of the global Gender Gap Index.
AB  - Reducing maternal mortality has been a crucial part of the global development
      agenda. According to modernisation theory, the effect of gender equality on
      maternal health may differ depending on a country's economic development status.
      We explored the correlation between the Global Gender Gap Index (GGI) provided by
      the World Economic Forum and the maternal mortality ratio (MMR) obtained from the
      World Development Indicators database of the World Bank. The relationships
      between each score in the GGI, including its four sub-indices (measuring gender
      gaps in economic participation, educational attainment, health and survival, and
      political empowerment), and the MMR were analysed. When the countries were
      stratified by gross national income per capita, the low and lower-middle-income
      countries had lower scores in the GGI, and lower scores in the economic
      participation, educational attainment, and political empowerment sub-indices than
      the high-income group. Among the four sub-indices, the educational attainment sub
      index showed a significant inverse correlation with the MMR in low and lower
      middle-income countries when controlling for the proportion of skilled birth
      attendance and public share of health expenditure. This finding suggests that
      strategic efforts to reduce the gender gap in educational attainment could lead
      to improvements in maternal health in low and lower-middle-income countries.

PMID- 27021476
TI  - [Hepatopulmonary syndrome].
AB  - Hepatopulmonary syndrome (HPS) is defined by the association of portal
      hypertension, increased alveolar-arterial oxygen gradient and intrapulmonary
      vascular dilations. Pathophysiological mechanisms of hypoxemia are characterized
      by ventilation-perfusion mismatch, oxygen diffusion limitation between alveolus
      and the centre of the dilated capillary, and right-to-left shunting. An excess of
      vasodilator molecules (like nitric monoxide) and proangiogenic factors (like
      VEGF) play an important role in the occurrence of HPS. Symptoms of HPS are not
      specific and dominated by a progressive dyspnea in upright position. Pulse
      oximetry is a simple non-invasive screening test but only detect the most severe
      forms of HPS. Medical treatment is disappointing and only liver transplantation
      may lead to resolution of HPS. Survival following liver transplantation is
      promising when hypoxemia is not severely decreased. 

PMID- 27021477
TI  - [Cryptococcal meningitis: It is not only an AIDS-associated disease].

PMID- 27021478
TI  - [Inguinolabial hernia of the uterus in women].

PMID- 27021479
TI  - [Acute cardiovascular disease and job retention].
AB  - Since it allows a better quality of life, return to work must be considered ever
      since the early stages of the health care pathway following a cardiovascular
      disease. Seeing the occupational physician beforehand, so as to anticipate the
      return to work, is crucial. Dialogue between cardiologists, general practitioners
      and occupational physician, still observing medical confidentiality, must allow a
      better quality of return to work. Being recognized as a handicapped worker is a
      key element in the prevention of socio-professional exclusion. Even when dealing
      with long sick leave, permanent functional injuries or job loss, guiding the
      patients towards the appropriate person can improve return to work and job
      retention in the long term. 

PMID- 27021480
TI  - [Management of excreta from elderly treated with antineoplastic drugs].
AB  - The excreta management of elderly patients treated by chemotherapy is not
      regularly dealt by a pragmatic process depending cancer treatments. It involves
      identifying the excreta toxicity, including their chemical classification,
      cytotoxic nature, renal or fecal exposition time of the drugs. Protective
      measures must be described to avoid the risk of contact with potentially
      contaminated excreta by anticancer drugs or their metabolites. To reduce the
      risk, information and training are essential. Medical monitoring professionals
      must be specific. The information must be extended to the patient and his
      entourage. 

PMID- 27021481
TI  - Non-surgical versus surgical treatment for oesophageal cancer.
AB  - BACKGROUND: Oesophageal cancer is the sixth most common cause of cancer-related
      mortality in the world. Currently surgery is the recommended treatment modality
      when possible. However, it is unclear whether non-surgical treatment options is
      equivalent to oesophagectomy in terms of survival. OBJECTIVES: To assess the
      benefits and harms of non-surgical treatment versus oesophagectomy for people
      with oesophageal cancer. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index,
      ClinicalTrials.gov, and the World Health Organization International Clinical
      Trials Registry Platform (WHO ICTRP) up to 4th March 2016. We also screened
      reference lists of included studies. SELECTION CRITERIA: Two review authors
      independently screened all titles and abstracts of articles obtained from the
      literature searches and selected references for further assessment. For these
      selected references, we based trial inclusion on assessment of the full-text
      articles. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted study data. We calculated the risk ratio (RR) with 95% confidence
      interval (CI) for binary outcomes, the mean difference (MD) or the standardised
      mean difference (SMD) with 95% CI for continuous outcomes, and the hazard ratio
      (HR) for time-to-event outcomes. We performed meta-analyses where it was
      meaningful. MAIN RESULTS: Eight trials, which included 1132 participants in
      total, met the inclusion criteria of this Cochrane review. These trials were at
      high risk of bias trials. One trial (which included five participants) did not
      contribute any data to this Cochrane review, and we excluded 13 participants in
      the remaining trials after randomisation; this left a total of 1114 participants,
      510 randomised to non-surgical treatment and 604 to surgical treatment for
      analysis. The non-surgical treatment was definitive chemoradiotherapy in five
      trials and definitive radiotherapy in three trials. All participants were
      suitable for major surgery. Most of the data were from trials that compared
      chemoradiotherapy with surgery. There was no difference in long-term mortality
      between chemoradiotherapy and surgery (HR 0.88, 95% CI 0.76 to 1.03; 602
      participants; four studies; low quality evidence). The long-term mortality was
      higher in radiotherapy than surgery (HR 1.39, 95% CI 1.18 to 1.64; 512
      participants; three studies; very low quality evidence). There was no difference
      in long-term recurrence between non-surgical treatment and surgery (HR 0.96, 95%
      CI 0.80 to 1.16; 349 participants; two studies; low quality evidence). The
      difference between non-surgical and surgical treatments was imprecise for short
      term mortality (RR 0.39, 95% CI 0.11 to 1.35; 689 participants; five studies;
      very low quality evidence), the proportion of participants with serious adverse
      in three months (RR 0.61, 95% CI 0.25 to 1.47; 80 participants; one study; very
      low quality evidence), and proportion of people with local recurrence at maximal
      follow-up (RR 0.89, 95% CI 0.70 to 1.12; 449 participants; three studies; very
      low quality evidence). The health-related quality of life was higher in non
      surgical treatment between four weeks and three months after treatment (Spitzer
      Quality of Life Index; MD 0.93, 95% CI 0.24 to 1.62; 165 participants; one study;
      very low quality evidence). The difference between non-surgical and surgical
      treatments was imprecise for medium-term health-related quality of life (three
      months to two years after treatment) (Spitzer Quality of Life Index; MD -0.95,
      95% CI -2.10 to 0.20; 62 participants; one study; very low quality of evidence).
      The proportion of people with dysphagia at the last follow-up visit prior to
      death was higher with definitive chemoradiotherapy compared to surgical treatment
      (RR 1.48, 95% CI 1.01 to 2.19; 139 participants; one study; very low quality
      evidence). AUTHORS' CONCLUSIONS: Based on low quality evidence, chemoradiotherapy
      appears to be at least equivalent to surgery in terms of short-term and long-term
      survival in people with oesophageal cancer (squamous cell carcinoma type) who are
      fit for surgery and are responsive to induction chemoradiotherapy. However, there
      is uncertainty in the comparison of definitive chemoradiotherapy versus surgery
      for oesophageal cancer (adenocarcinoma type) and we cannot rule out significant
      benefits or harms of definitive chemoradiotherapy versus surgery. Based on very
      low quality evidence, the proportion of people with dysphagia at the last follow
      up visit prior to death was higher with definitive chemoradiotherapy compared to
      surgery. Based on very low quality evidence, radiotherapy results in less long
      term survival than surgery in people with oesophageal cancer who are fit for
      surgery. However, there is a risk of bias and random errors in these results,
      although the risk of bias in the studies included in this systematic review is
      likely to be lower than in non-randomised studies.Further trials at low risk of
      bias are necessary. Such trials need to compare endoscopic treatment with
      surgical treatment in early stage oesophageal cancer (carcinoma in situ and Stage
      Ia), and definitive chemoradiotherapy with surgical treatments in other stages of
      oesophageal cancer, and should measure and report patient-oriented outcomes.
      Early identification of responders to chemoradiotherapy and better second-line
      treatment for non-responders will also increase the need and acceptability of
      trials that compare definitive chemoradiotherapy with surgery.

PMID- 27021482
TI  - Antibiotics and antiseptics for surgical wounds healing by secondary intention.
AB  - BACKGROUND: Following surgery, incisions are usually closed by fixing the edges
      together with sutures (stitches), staples, adhesives (glue) or clips. This
      process helps the cut edges heal together and is called 'healing by primary
      intention'. However, a minority of surgical wounds are not closed in this way.
      Where the risk of infection is high or there has been significant loss of tissue,
      wounds may be left open to heal by the growth of new tissue rather than by
      primary closure; this is known as 'healing by secondary intention'. There is a
      risk of infection in open wounds, which may impact on wound healing, and
      antiseptic or antibiotic treatments may be used with the aim of preventing or
      treating such infections. This review is one of a suite of Cochrane reviews
      investigating the evidence on antiseptics and antibiotics in different types of
      wounds. It aims to present current evidence related to the use of antiseptics and
      antibiotics for surgical wounds healing by secondary intention (SWHSI).
      OBJECTIVES: To assess the effects of systemic and topical antibiotics, and
      topical antiseptics for the treatment of surgical wounds healing by secondary
      intention. SEARCH METHODS: In November 2015 we searched: The Cochrane Wounds
      Specialised Register; The Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other
      Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched three
      clinical trials registries and the references of included studies and relevant
      systematic reviews. There were no restrictions with respect to language, date of
      publication or study setting. SELECTION CRITERIA: Randomised controlled trials
      which enrolled adults with a surgical wound healing by secondary intention and
      assessed treatment with an antiseptic or antibiotic treatment. Studies enrolling
      people with skin graft donor sites were not included, neither were studies of
      wounds with a non-surgical origin which had subsequently undergone sharp or
      surgical debridement or other surgical treatments or wounds within the oral or
      aural cavities. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed study selection, risk of bias assessment and data extraction. MAIN
      RESULTS: Eleven studies with a total of 886 participants were included in the
      review. These evaluated a range of comparisons in a range of surgical wounds
      healing by secondary intention. In general studies were small and some did not
      present data or analyses that could be easily interpreted or related to clinical
      outcomes. These factors reduced the quality of the evidence.Two comparisons
      compared different iodine preparations with no antiseptic treatment and found no
      clear evidence of effects for these treatments. The outcome data available were
      limited and what evidence there was low quality.One study compared a zinc oxide
      mesh dressing with a plain mesh dressing. There was no clear evidence of a
      difference in time to wound healing between groups. There was some evidence of a
      difference in measures used to assess wound infection (wound with foul smell and
      number of participants prescribed antibiotics) which favoured the zinc oxide
      group. This was low quality evidence.One study reported that sucralfate cream
      increased the likelihood of healing open wounds following haemorrhoidectomy
      compared to a petrolatum cream (RR: 1.50, 95% CI 1.13 to 1.99) over a three week
      period. This evidence was graded as being of moderate quality. The study also
      reported lower wound pain scores in the sucralfate group.There was a reduction in
      time to healing of open wounds following haemorrhoidectomy when treated with
      Triclosan post-operatively compared with a standard sodium hypochlorite solution
      (mean difference -1.70 days, 95% CI -3.41 to 0.01). This was classed as low
      quality evidence.There was moderate quality evidence that more open wounds
      resulting from excision of pyomyositis abscesses healed when treated with a honey
      soaked gauze compared with a EUSOL-soaked gauze over three weeks' follow-up (RR:
      1.58, 95% CI 1.03 to 2.42). There was also some evidence of a reduction in the
      mean length of hospital stay in the honey group. Evidence was taken from one
      small study that only had 43 participants.There was moderate quality evidence
      that more Dermacym(r)-treated post-operative foot wounds in people with diabetes
      healed compared to those treated with iodine (RR 0.61, 95% CI 0.40 to 0.93).
      Again estimates came from one small study with 40 participants. AUTHORS'
      CONCLUSIONS: There is no robust evidence on the relative effectiveness of any
      antiseptic/antibiotic/anti-bacterial preparation evaluated to date for use on
      SWHSI. Where some evidence for possible treatment effects was reported, it
      stemmed from single studies with small participant numbers and was classed as
      moderate or low quality evidence. This means it is likely or very likely that
      further research will have an important impact on our confidence in the estimate
      of effect, and may change this estimate.

PMID- 27021483
TI  - Growth and reproduction of the highfin grouper Epinephelus maculatus.
AB  - Highfin grouper Epinephelus maculatus sampled in Chuuk, Micronesia, exhibited a
      moderate growth rate and a relatively short life span compared to other
      epinephelids of a similar size. Combined gonad and otolith analysis provide
      preliminary evidence that the species conforms to a protogynous sexual pattern.
      Mean total length at maturity for females was 308 mm with first age at maturity
      2.8 years for females and 4 years for males, which differs from other regional
      studies. Based on the gonado-somatic index and microscopic analysis of gonads, E.
      maculatus in Chuuk have a 4 month spawning season (January to April) that
      corresponds with seasonal lows in sea surface water temperature and overlaps with
      that of other aggregating epinephelids. The estimated von Bertalanffy growth
      factor (K) was 0.51 year(-1) , while total mortality was 0.34 year(-1) . Current
      management for E. maculatus in Chuuk includes a January to May catch, sale and
      export ban, which overlaps with its reproductive season. The effectiveness of
      these arrangements will require on-going monitoring to determine whether
      alternative management strategies are required to ensure population persistence. 

PMID- 27021484
TI  - The Ec-NhaA antiporter switches from antagonistic to synergistic antiport upon a
      single point mutation.
AB  - The Na(+), Li(+)/H(+) antiporter of Escherichia coli (Ec-NhaA) maintains pH,
      Na(+) homeostasis in enterobacteria. We used isothermal titration calorimetry to
      perform a detailed thermodynamic analysis of Li(+) binding to Ec-NhaA and several
      of its mutants. We found that, in line with the canonical alternative access
      mechanistic model of secondary transporters, Li(+)/H(+) binding to the antiporter
      is antagonistically coupled. Binding of Li(+) displaces 2 H(+) from the binding
      site. The process is enthalpically driven, the enthalpic gain just compensating
      for an entropic loss and the buffer-associated enthalpic changes dominate the
      overall free-energy change. Li(+) binding, H(+) release and antiporter activity
      were all affected to the same extent by mutations in the Li(+) binding site
      (D163E, D163N, D164N, D164E), while D133C changed the H(+)/Li(+) stoichiometry to
      4. Most striking, however, was the mutation, A167P, which converted the Ec-NhaA
      antagonistic binding into synergistic binding which is only known to occur in Cl(
      )/H(+) antiporter. 

PMID- 27021487
TI  - Women's perceptions of biases and barriers in their myocardial infarction triage
      experience.
AB  - OBJECTIVE: To examine women's perceptions of their emergency department (ED)
      cardiac triage experience for myocardial infarction (MI). BACKGROUND: Prompt ED
      recognition and rapid triage of women is a key component of implementing life
      saving interventions for acute MI. Women perceive their symptoms are often
      ignored by health care providers and not taken seriously. METHODS: A qualitative
      study was conducted using focus group methodology. Narrative descriptions were
      transcribed verbatim and analyzed using the Krueger method. RESULTS: Content
      analysis revealed perceptions of support and barriers. Supports included ED
      providers and ED status. Barriers were time delays, communication issues, and
      biases based on age and gender. These perceived barriers contributed to women's
      perceptions of disparate treatment. CONCLUSIONS: Women with MI perceived multiple
      barriers to their prompt recognition and treatment. Evaluation of care delivery
      processes are needed to reduce barriers and facilitate the prompt and accurate
      treatment of women for MI.

PMID- 27021486
TI  - Cell and Gene Therapy for the Beta-Thalassemias: Advances and Prospects.
AB  - The beta-thalassemias are inherited anemias caused by mutations that severely
      reduce or abolish expression of the beta-globin gene. Like sickle cell disease, a
      related beta-globin gene disorder, they are ideal candidates for performing a
      genetic correction in patient hematopoietic stem cells (HSCs). The most advanced
      approach utilizes complex lentiviral vectors encoding the human beta-globin gene,
      as first reported by May et al. in 2000. Considerable progress toward the
      clinical implementation of this approach has been made in the past five years,
      based on effective CD34+ cell mobilization and improved lentiviral vector
      manufacturing. Four trials have been initiated in the United States and Europe.
      Of 16 evaluable subjects, 6 have achieved transfusion independence. One of them
      developed a durable clonal expansion, which regressed after several years without
      transformation. Although globin lentiviral vectors have so far proven to be safe,
      this occurrence suggests that powerful insulators with robust enhancer-blocking
      activity will further enhance this approach. The combined discovery of Bcl11a
      mediated gamma-globin gene silencing and advances in gene editing are the
      foundations for another gene therapy approach, which aims to reactivate fetal
      hemoglobin (HbF) production. Its clinical translation will hinge on the safety
      and efficiency of gene targeting in true HSCs and the induction of sufficient
      levels of HbF to achieve transfusion independence. Altogether, the progress
      achieved over the past 15 years bodes well for finding a genetic cure for severe
      globin disorders in the next decade. 

PMID- 27021488
TI  - Building partnerships to reduce heart disease in women.

PMID- 27021490
TI  - StrucBreak: A Computational Framework for Structural Break Detection in DNA
      Sequences.
AB  - Damages or breaks in DNA may change the characteristics of genomes and causes
      various diseases. In this work we construct a system that incorporates the
      maximum likelihood-based probabilistic formula to assess the number of damages
      that have occurred in any DNA sequence. This approach has been progressively
      benchmarked by implementing simulated data sets so that the outcomes can be
      compared with a ground truth or reference value. At first the sequence data set
      order is checked through the statistical cumulative sum (STACUMSUM). The verified
      sequences are then estimated by prior and posterior probability to count the
      percentages of breaks and mutations. Maximum-likelihood estimation then finds out
      the exact numbers and positions of breaks and detections. In database
      manipulation, one factor that decides the orientation and order of the sequence
      is geometric distance between consecutive sequences. The geometric distance is
      measured for smooth representation of the genome or DNA sequences. Finally, we
      compared the performance of our system with DAMBE5: (A Comprehensive Software
      Package for Data Analysis in Molecular Biology and Evaluation), and in response
      to time and space complexity, StrucBreak is much faster and consumes much less
      space due to our algorithmic approaches.

PMID- 27021491
TI  - microRNAs Databases: Developmental Methodologies, Structural and Functional
      Annotations.
AB  - microRNA (miRNA) is an endogenous and evolutionary conserved non-coding RNA,
      involved in post-transcriptional process as gene repressor and mRNA cleavage
      through RNA-induced silencing complex (RISC) formation. In RISC, miRNA binds in
      complementary base pair with targeted mRNA along with Argonaut proteins complex,
      causes gene repression or endonucleolytic cleavage of mRNAs and results in many
      diseases and syndromes. After the discovery of miRNA lin-4 and let-7,
      subsequently large numbers of miRNAs were discovered by low-throughput and high
      throughput experimental techniques along with computational process in various
      biological and metabolic processes. The miRNAs are important non-coding RNA for
      understanding the complex biological phenomena of organism because it controls
      the gene regulation. This paper reviews miRNA databases with structural and
      functional annotations developed by various researchers. These databases contain
      structural and functional information of animal, plant and virus miRNAs including
      miRNAs-associated diseases, stress resistance in plant, miRNAs take part in
      various biological processes, effect of miRNAs interaction on drugs and
      environment, effect of variance on miRNAs, miRNAs gene expression analysis,
      sequence of miRNAs, structure of miRNAs. This review focuses on the developmental
      methodology of miRNA databases such as computational tools and methods used for
      extraction of miRNAs annotation from different resources or through experiment.
      This study also discusses the efficiency of user interface design of every
      database along with current entry and annotations of miRNA (pathways, gene
      ontology, disease ontology, etc.). Here, an integrated schematic diagram of
      construction process for databases is also drawn along with tabular and graphical
      comparison of various types of entries in different databases. Aim of this paper
      is to present the importance of miRNAs-related resources at a single place.

PMID- 27021489
TI  - Old cells, new tricks: chromatin structure in senescence.
AB  - Cellular senescence is a stable form of cell cycle arrest with roles in many
      pathophysiological processes including development, tissue repair, cancer, and
      aging. Senescence does not represent a single entity but rather a heterogeneous
      phenotype that depends on the trigger and cell type of origin. Such heterogeneous
      features include alterations to chromatin structure and epigenetic states. New
      technologies are beginning to unravel the distinct mechanisms regulating
      chromatin structure during senescence. Here, we describe the multiple levels of
      chromatin organization associated with senescence: global and focal, linear, and
      higher order.

PMID- 27021492
TI  - A preclinical murine model for the early detection of radiation-induced brain
      injury using magnetic resonance imaging and behavioral tests for learning and
      memory: with applications for the evaluation of possible stem cell imaging agents
      and therapies.
AB  - Stem cell therapies are being developed for radiotherapy-induced brain injuries
      (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging
      transplanted stem cells. However, most MRI cell-tracking techniques employ
      superparamagnetic iron oxide particles (SPIOs), which are difficult to
      distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage
      occurs concurrently with other injury markers. This makes the evaluation of the
      recruitment of transplanted SPIO-labeled stem cells to injury sites difficult.
      Here, we developed a RIBI model, with early injury markers reflective of
      hippocampal dysfunction, which can be detected noninvasively with MRI and
      behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse
      hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with
      anatomical and contrast-enhanced MRI and changes in memory and learning were
      assessed with fear-conditioning tests. Early injury markers were detected 2 weeks
      after irradiation. These included an increase in the permeability of the blood
      brain barrier, demonstrated by a 92 +/- 20 % contrast enhancement of the
      irradiated versus the non-irradiated brain hemispheres, within 15 min of the
      administration of an MRI contrast agent. A change in short-term memory was also
      detected, as demonstrated by a 40.88 +/- 5.03 % decrease in the freezing time
      measured during the short-term memory context test at this time point, compared
      to that before irradiation. SPIO-labeled stem cells transplanted contralateral to
      the lesion migrated toward the lesion at this time point. No hemorrhage was
      detected up to 10 weeks after irradiation. This model can be used to evaluate
      SPIO-based stem cell-tracking agents, short-term.

PMID- 27021493
TI  - Sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission tomography for
      advanced colorectal neoplasms: a large-scale analysis of 7505 asymptomatic
      screening individuals.
AB  - BACKGROUND: The sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission
      tomography (FDG-PET) for advanced colorectal neoplasms among healthy subjects is
      not yet fully understood. The present study aimed to clarify the sensitivity by
      analyzing large-scale data from an asymptomatic screening population. METHODS: A
      total of 7505 asymptomatic screenees who underwent both FDG-PET and colonoscopy
      at our Cancer Screening Division between February 2004 and March 2013 were
      analyzed. FDG-PET and colonoscopy were performed on consecutive days, and each
      examination was interpreted in a blinded fashion. The results of the two
      examinations were compared for each of the divided six colonic segments, with
      those from colonoscopy being set as the reference. The relationships between the
      sensitivity of FDG-PET and clinicopathological features of advanced neoplasms
      were also evaluated. RESULTS: Two hundred ninety-one advanced neoplasms,
      including 24 invasive cancers, were detected in 262 individuals. Thirteen
      advanced neoplasms (advanced adenomas) were excluded from the analysis because of
      the coexistence of lesions in the same colonic segment. The sensitivity,
      specificity, and positive and negative predictive values of FDG-PET for advanced
      neoplasms were 16.9 % [95 % confidence interval (CI) 12.7-21.8 %], 99.3 % (95 %
      CI 99.2-99.4 %), 13.5 % (95 % CI 10.1-17.6 %), and 99.4 % (95 % CI 99.3-99.5 %),
      respectively. The sensitivity was lower for lesions with less advanced
      histological grade, of smaller size, and flat-type morphology, and for those
      located in the proximal part of the colon. CONCLUSIONS: FDG-PET is believed to be
      difficult to use as a primary screening tool in population-based colorectal
      cancer screening because of its low sensitivity for advanced neoplasms. Even when
      it is used in opportunistic cancer screening, the limit of its sensitivity should
      be considered.

PMID- 27021495
TI  - Comparative study of adverse events after yellow fever vaccination between
      elderly and non-elderly travellers: questionnaire survey in Japan over a 1-year
      period.
AB  - BACKGROUND: A live attenuated yellow fever (YF) vaccination is required of all
      travellers visiting countries where YF virus is endemic. Although the risk of
      serious adverse events (AEs) after YF vaccination is known to be greater in
      elderly people than in younger people, information about other AEs among elderly
      travellers is lacking. METHODS: A prospective observational questionnaire study
      was conducted to investigate the occurrence of AEs after YF vaccination in
      travellers who attended a designated YF vaccination centre in Tokyo, Japan, from
      1 November 2011 to 31 October 2012. A questionnaire enquiring about any AEs
      experienced in the 2 weeks following YF vaccination was distributed to all
      vaccinees enrolled in this study, and responses were collected subsequently by
      mail or phone. For child vaccinees, their parents were allowed to respond in
      their stead. RESULTS: Of the 1298 vaccinees who received the YF vaccine, 1044
      (80.4%) were enrolled in the present study and 666 (63.8%) responded to the
      questionnaire. Of these 666 respondents, 370 (55.6%) reported AEs, of which 258
      (38.7%) were systemic and 230 (34.5%) were local. No severe AEs associated with
      YF vaccination were reported. Elderly vaccinees (aged >=60 years) reported fewer
      total AEs than those aged <60 years (42.9% vs 60.3%;P < 0.001). CONCLUSION: Our
      study showed that fewer general AEs after yellow vaccination reported among
      elderly vaccinees than among non-elderly vaccinees. These results could provide
      supplementary information for judging the adaptation of vaccination in elderly
      travellers.

PMID- 27021494
TI  - Brain 2-Arachidonoylglycerol Levels Are Dramatically and Rapidly Increased Under
      Acute Ischemia-Injury Which Is Prevented by Microwave Irradiation.
AB  - The involvement of brain 2-arachidonoylglycerol (2-AG) in a number of critical
      physiological and pathophysiological regulatory mechanisms highlights the
      importance for an accurate brain 2-AG determination. In the present study, we
      validated head-focused microwave irradiation (MW) as a method to prevent
      postmortem brain 2-AG alterations before analysis. We compared MW to freezing to
      prevent 2-AG induction and estimated exogenous and endogenous 2-AG stability upon
      exposure to MW. Using MW, we measured, for the first time, true 2-AG brain levels
      under basal conditions, 30 s after brain removal from the cranium, and upon
      exposure to 5 min of brain global ischemia. Our data indicate that brain 2-AG
      levels are instantaneously and dramatically increased approximately 60-fold upon
      brain removal from the cranium. With 5 min of brain global ischemia 2-AG levels
      are also, but less dramatically, increased 3.5-fold. Our data indicate that brain
      tissue fixation with MW is a required technique to measure both true basal 2-AG
      levels and 2-AG alterations under different experimental conditions including
      global ischemia, and 2-AG is stable upon exposure to MW.

PMID- 27021496
TI  - Shewanella algae bacteremia from a foot ulcer exposed to seawater during a
      Caribbean vacation.

PMID- 27021497
TI  - Enquiries to the United Kingdom National Travel Advice Line by healthcare
      professionals regarding immunocompromised travellers.
AB  - BACKGROUND: People who travel while immunocompromised are more at risk of serious
      travel-related infection. Their condition, medications or treatments can
      contraindicate, decrease the effectiveness of or increase the toxicity of
      vaccinations or malaria chemoprophylaxis. Therefore, immunocompromised travellers
      require careful assessment and specialized pre-travel advice. The aims of this
      study were to investigate enquiries by healthcare professionals (HCPs) to the UK
      National Travel Health Network and Centre (NaTHNaC) advice line regarding
      travellers with immunocompromise and to identify their most common concerns.
      METHODS: Documentation for all calls taken by advisers at the London office
      during 2013 was reviewed. RESULTS: Of the 4910 enquiries to the London NaTHNaC
      advice line, 397 calls concerned immunocompromised travellers (8.1%). The
      majority of immunocompromised travellers were planning to visit Sub-Saharan
      Africa (53%) for the purpose of tourism (43%). Sixty-seven percent of enquiries
      concerned vaccine use, 11% were about malaria chemoprophylaxis, 20% were about
      both and 2% were for other reasons. Causes of immunocompromise included
      inflammatory or autoimmune conditions (43%), cancer (18%), splenic dysfunction
      (13%), immunosuppressive drugs (12%), human immunodeficiency virus (11%), primary
      immunodeficiency (1%), neutropenia (0.5%) and thymus abnormalities (0.5%).
      CONCLUSIONS: There were frequent enquires to the advice line by UK HCPs regarding
      immunocompromised travellers. The travellers in this study had a wide range of
      underlying medical conditions and varying levels of immunocompromise. These
      enquiries may reflect a lack of clarity in current national guidelines,
      difficulties in interpreting them or both. Establishing the reasons for these
      deficiencies as well as the reasons behind UK HCP concerns and lack of confidence
      requires further investigation. This research has highlighted potential knowledge
      gaps and will help inform future guidance and educational activities for UK HCPs
      advising travellers.

PMID- 27021498
TI  - Paederus dermatitis in a seafarer diagnosed via telemedicine collaboration.
AB  - Seafarers are traveling workers, subject to unique exposures and generally
      isolated from adequate medical care. This case report of paederus dermatitis
      diagnosed at sea highlights the importance of a multidisciplinary diagnostic
      approach and telecommunication in providing remote medical advice to isolated
      traveling workers such as seafarers. 

PMID- 27021499
TI  - The role of neutrophils in inflammation resolution.
AB  - The fundamental role played by neutrophils for an efficient, acute inflammatory
      response has long been appreciated, with the underlying molecular and cellular
      mechanisms largely elucidated over the past decades. However, more recent work
      suggests that the biological functions exerted by this fascinating leucocyte are
      somewhat more extensive than previously acknowledged. Here we discuss how
      extravasated neutrophils govern the initiation of the resolution phase of
      inflammation by enabling activation of pro-resolving circuits to ensure the safe
      conclusion of the inflammatory response. The neutrophil 'alarm bell' on
      resolution is effected through release of soluble mediators as well as apoptotic
      bodies and other vesicles, which, in turn, can inform and modify the
      microenvironment ultimately leading to termination of the inflammatory response
      coinciding with re-establishment of tissue homeostasis and functionality.

PMID- 27021501
TI  - Effect of Functional Status on the Quality of Bowel Preparation in Elderly
      Patients Undergoing Screening and Surveillance Colonoscopy.
AB  - BACKGROUND/AIMS: Optimal bowel preparation is essential for successful screening
      or for surveillance colonoscopy (SC). Inadequate bowel preparation is associated
      with older age, the male gender, and the presence of certain comorbidities.
      However, the association between patients' functional status and bowel
      preparation quality has not been studied. We prospectively examined the
      relationship between functional status, namely, the ability to perform activities
      of daily living (ADLs) and ambulate, and the quality of bowel preparation in
      elderly patients undergoing SC. METHODS: Before undergoing SC, 88 elderly
      patients were surveyed regarding their functional status, specifically regarding
      their ability to perform ADLs and ambulate a quarter of a mile.
      Gastroenterologists then determined the quality of the bowel preparation, which
      was classified as either adequate or inadequate. Then, the frequency of
      inadequate bowel preparation in patients who did or did not experience difficulty
      performing ADLs and ambulating was calculated. RESULTS: Difficulty ambulating
      (unadjusted odds ratio [OR], 4.83; p<0.001), difficulty performing ADLs (OR,
      2.93; p=0.001), and history of diabetes (OR, 2.88; p=0.007) were significant
      univariate predictors of inadequate bowel preparation. After adjusting for the
      above variables, only difficulty ambulating (adjusted OR, 5.78; p=0.004) was an
      independent predictor of inadequate bowel preparation. CONCLUSIONS: Difficulty
      with ambulation is a strong predictor of inadequate bowel preparation in elderly
      patients undergoing SC.

PMID- 27021500
TI  - Complement inhibition in pre-clinical models of periodontitis and prospects for
      clinical application.
AB  - Periodontitis is a dysbiotic inflammatory disease leading to the destruction of
      the tooth-supporting tissues. Current therapies are not always effective and this
      prevalent oral disease continues to be a significant health and economic burden.
      Early clinical studies have associated periodontitis with elevated complement
      activity. Consistently, subsequent genetic and pharmacological studies in rodents
      have implicated the central complement component C3 and downstream signaling
      pathways in periodontal host-microbe interactions that promote dysbiosis and
      inflammatory bone loss. This review discusses these mechanistic advances and
      moreover focuses on the compstatin family of C3 inhibitors as a novel approach to
      treat periodontitis. In this regard, local application of the current lead analog
      Cp40 was recently shown to block both inducible and naturally occurring
      periodontitis in non-human primates. These promising results from non-human
      primate studies and the parallel development of Cp40 for clinical use highlight
      the feasibility for developing an adjunctive, C3-targeted therapy for human
      periodontitis.

PMID- 27021502
TI  - The Wire-Grasping Method as a New Technique for Forceps Biopsy of Biliary
      Strictures: A Prospective Randomized Controlled Study of Effectiveness.
AB  - BACKGROUND/AIMS: Transpapillary forceps biopsy is an effective diagnostic
      technique in patients with biliary stricture. This prospective study aimed to
      determine the usefulness of the wire-grasping method as a new technique for
      forceps biopsy. METHODS: Consecutive patients with biliary stricture or
      irregularities of the bile duct wall were randomly allocated to either the direct
      or wire-grasping method group. In the wiregrasping method, forceps in the
      duodenum grasps a guidewire placed into the bile duct beforehand, and then, the
      forceps are pushed through the papilla without endoscopic sphincterotomy. In the
      direct method, forceps are directly pushed into the bile duct alongside a guide
      wire. The primary endpoint was the success rate of obtaining specimens suitable
      for adequate pathological examination. RESULTS: In total, 32 patients were
      enrolled, and 28 (14 in each group) were eligible for analysis. The success rate
      was significantly higher using the wire-grasping method than the direct method
      (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were
      comparable in patients with the successful procurement of biopsy specimens
      between the two methods (91% vs 83% and 93% vs 86%, respectively). CONCLUSIONS:
      The wire-grasping method is useful for diagnosing patients with biliary stricture
      or irregularities of the bile duct wall.

PMID- 27021503
TI  - Risk of Clostridium difficile Infection with the Use of a Proton Pump Inhibitor
      for Stress Ulcer Prophylaxis in Critically Ill Patients.
AB  - BACKGROUND/AIMS: Proton pump inhibitors (PPIs) and histamine-2 receptor
      antagonists (H2RAs) are commonly prescribed for stress ulcer prophylaxis (SUP) in
      critically ill patients. Several studies have suggested that the use of PPIs is a
      potential risk factor for Clostridium difficile infection (CDI). We compared the
      incidences of CDI in the PPI group and H2RA group for SUP in critically ill
      patients. METHODS: From August 2005 to July 2012, the incidences of CDI were
      retrospectively analyzed in patients who were admitted directly to intensive care
      units and stayed for more than 3 days. SUP-related CDI was defined as a CDI
      diagnosed during the SUP period. Patient clinical data were analyzed to identify
      potential risk factors for SUP-related CDI. RESULTS: Of the 1,005 patients
      enrolled (444 patients received PPI and 561 received H2RA), 38 (3.8%) were
      diagnosed with SUP-related CDI. The incidence of SUP-related CDI was considerably
      higher in patients who received PPI than in those who received H2RA (6.7% vs
      1.8%). PPI use for SUP (odds ratio [OR], 3.3; confidence interval [CI], 1.5 to
      7.1; p=0.003) and diabetes mellitus (OR, 2.3; CI, 1.2 to 4.7; p=0.019) were
      independent risk factors for SUP-related CDI. CONCLUSIONS: PPI therapy is
      associated with a higher risk of SUP-related CDI than H2RA therapy in critically
      ill patients.

PMID- 27021504
TI  - Magnifying Endoscopy with Narrow Band Imaging of Early Gastric Cancer:
      Correlation with Histopathology and Mucin Phenotype.
AB  - BACKGROUND/AIMS: Magnifying endoscopy with narrow band imaging (ME-NBI) is a
      useful modality for the detailed visualization of microsurface (MS) and
      microvascular (MV) structures in the gastrointestinal tract. This study aimed to
      determine whether the MS and MV patterns in ME-NBI differ according to the
      histologic type, invasion depth, and mucin phenotype of early gastric cancers
      (EGCs). METHODS: The MS and MV patterns of 160 lesions in 160 patients with EGC
      who underwent ME-NBI before endoscopic or surgical resection were prospectively
      collected and analyzed. EGCs were categorized as either differentiated or
      undifferentiated and as either mucosal or submucosal, and their mucin phenotypes
      were determined via immunohistochemistry of the tumor specimens. RESULTS:
      Differentiated tumors mainly displayed an oval and/or tubular MS pattern and a
      fine network or loop MV pattern, whereas undifferentiated tumors mainly displayed
      an absent MS pattern and a corkscrew MV pattern. The destructive MS pattern was
      associated with submucosal invasion, and this association was more prominent in
      the differentiated tumors than in the undifferentiated tumors. MUC5AC expression
      was increased in lesions with either a papillary or absent MS pattern and a
      corkscrew MV pattern, whereas MUC6 expression was increased in lesions with a
      papillary MS pattern and a loop MV pattern. CD10 expression was more frequent in
      lesions with a fine network MV pattern. CONCLUSIONS: ME-NBI can be useful for
      predicting the histopathology and mucin phenotype of EGCs.

PMID- 27021505
TI  - Comparison of the Efficacies of Parenteral Iron Sucrose and Oral Iron Sulfate for
      Anemic Patients with Inflammatory Bowel Disease in Korea.
AB  - BACKGROUND/AIMS: The optimal route for iron administration in anemic patients
      with inflammatory bowel disease (IBD) has not been determined. The aim of this
      study was to compare the efficacies of parenteral and oral iron therapy in IBD
      patients in Korea. METHODS: A retrospective multicenter study was performed.
      Patients who had been administered parenteral iron were matched to the controls
      with oral iron at a 1:1 ratio according to age, sex, and type of IBD. RESULTS:
      Patients that received parenteral iron exhibited increases in hemoglobin levels
      of >=20% from the baseline at lower doses and in shorter durations (p=0.034 and
      p=0.046, respectively). In the multivariate analysis, parenteral iron therapy
      appeared to be more efficient than oral iron therapy, but this difference was not
      statistically significant (hazard ratio [HR], 1.552; 95% confidence interval
      [CI], 0.844 to 2.851; p=0.157). Patients with ulcerative colitis responded better
      to iron therapy than those with Crohn's disease (HR, 3.415; 95% CI, 1.808 to
      6.450; p<0.001). Patients with an initial hemoglobin level of 10 g/dL or higher
      responded poorly to iron therapy (HR, 0.345; 95% CI, 0.177 to 0.671; p=0.002).
      CONCLUSIONS: Parenteral iron therapy appears to be more efficient than oral iron
      therapy. Physicians should focus on the iron deficiency of IBD patients and
      consider parenteral iron supplements in appropriate patient groups.

PMID- 27021506
TI  - Disease Phenotype, Activity and Clinical Course Prediction Based on C-Reactive
      Protein Levels at Diagnosis in Patients with Crohn's Disease: Results from the
      CONNECT Study.
AB  - BACKGROUND/AIMS: C-reactive protein (CRP) is an easily measured index of disease
      activity, but its ability to predict clinical course is controversial. We
      therefore designed a study to determine whether the CRP level at Crohn's disease
      (CD) diagnosis is a valuable indicator of the disease phenotype, activity, and
      clinical course. METHODS: We retrospectively analyzed 705 CD patients from 32
      institutions. The patients were classified into two groups according to CRP
      level. The patients' demographic and clinical characteristics and their use of
      immunosuppressive or biological agents were recorded. Disease location and
      behavior, hospitalization, and surgery were analyzed. RESULTS: A high CRP was
      associated with younger age, steroid use, colonic or ileocolonic location, high
      CD activity index, and active inflammation at colonoscopy (p<0.001). As the
      disease progressed, patients with high CRP were more likely to exhibit strictures
      (p=0.027). There were significant differences in the use of 5-aminosalicylic
      acid, antibiotics, corticosteroids, azathioprine, and infliximab (p<0.001,
      p<0.001, p<0.001, p<0.001, and p=0.023, respectively). Hospitalization was also
      more frequent in patients with high CRP. CONCLUSIONS: The CRP level at diagnosis
      is useful for evaluating the phenotype, activity, and clinical course of CD.
      Closer follow-up strategies, with early aggressive treatment, could be considered
      for patients with high CRP.

PMID- 27021507
TI  - Bile Flow Phantom Model and Animal Bile Duct Dilation Model for Evaluating
      Biliary Plastic Stents with Advanced Hydrophilic Coating.
AB  - BACKGROUND/AIMS: The efforts to improve biliary plastic stents (PSs) for
      decreasing biofilm formation and overcome short patency time have been continued.
      The aim of this study is to evaluate the effect of advanced hydrophilic coating
      for patency and biodurability of PS. METHODS: Using an in vitro bile flow phantom
      model, we compared patency between prototype PS with hydrophilic coating (PS+HC)
      and prototype PS without hydrophilic coating (PS-HC). We performed an analysis of
      the degree of luminal narrowing by microscopic examination. Using an in vivo
      swine bile duct dilation model made by endoscopic papillary closure and stent
      insertion, we evaluated biodurability of hydrophilic coating. RESULTS: In the
      phantom model, PS+HC showed less biofilm formation and luminal narrowing than PS
      HC at 8 weeks (p<0.05). A total of 31 stents were inserted into the dilated bile
      duct of seven swine models, and 24 stents were successfully retrieved 8 weeks
      later. There was no statistical difference of stent patency between the
      polyethylene PS+HC and the polyurethane PS+HC. The biodurability of hydrophilic
      coating was sustained up to 8 weeks, when assessing the coating layer by scanning
      electron microscopy examination. CONCLUSIONS: Advanced hydrophilic coating
      technology may extend the patency of PS compared to uncoated PS.

PMID- 27021508
TI  - Parents' and staff's support for a childcare agency employee mandatory
      vaccination policy or agency certification program.
AB  - BACKGROUND: Vaccine-preventable diseases pose a significant risk to children in
      childcare. However, few regulations exist regarding childcare staff vaccination.
      This study aimed to assess support for a childcare agency staff mandatory
      vaccination policy. METHODS: Surveys were distributed to staff and parents at 23
      St Louis, Mo, childcare agencies during fall 2014. Staff and parents' support for
      a mandatory vaccination and/or agency certification program were compared using
      chi(2) tests. Multivariate logistic regression was conducted using a 2-level
      nested design and controlling for gender, race, age, and income to determine
      predictive models for support for a mandatory staff vaccination policy and/or
      agency certification program. RESULTS: Overall, 354 parents and staff
      participated (response rate, 32%). Most supported a mandatory staff vaccination
      policy (80.0%; n = 280) or agency certification program (81.2%; n = 285), and
      there were no differences between parents versus staff. Determinants of support
      for a mandatory policy included willingness to receive influenza vaccine
      annually, belief that vaccines are safe and effective, and support for the policy
      only if there were no costs. CONCLUSIONS: There is strong support for some type
      of childcare agency staff vaccination policy. Implementing such a policy/program
      should be a collaborative endeavor that addresses vaccine cost and access.

PMID- 27021509
TI  - Can carbapenem-resistant enterobacteriaceae susceptibility results obtained from
      surveillance cultures predict the susceptibility of a clinical carbapenem
      resistant enterobacteriaceae?
AB  - We evaluated the susceptibility profile of a colonizing carbapenem-resistant
      enterobacteriaceae to predict its susceptibility when recovered from a clinical
      specimen. An overall agreement of 88.7% (517 out of 583; 95% confidence interval,
      85.8%-91.0%) was observed for the combinations of 11 antibiotics with 53 pairs of
      Klebsiella pneumoniae carbapenemase-producing K pneumoniae (the only carbapenem
      resistant enterobacteriaceae detected). Very major errors were observed mainly
      for aminoglycoside agents and colistin, limiting the predictability of the
      susceptibility profile for these clinical isolates.

PMID- 27021510
TI  - Occupational exposure to bloodborne pathogens among health care workers in
      Botswana: Reporting and utilization of postexposure prophylaxis.
AB  - BACKGROUND: This study assessed reporting behavior and satisfaction with
      postexposure prophylaxis (PEP) systems among health care workers (HCWs) at risk
      for occupational bloodborne pathogen exposure (BPE) in 3 public hospitals in
      Botswana. METHODS: A cross-sectional survey among HCWs provided information on
      perceptions, attitudes, and experiences with occupational exposures, reporting,
      and postexposure care. HCWs potentially in contact with blood or body fluids were
      surveyed using audio computer-assisted self-interview. RESULTS: Between August
      2012 and April 2013, 1,624 HCWs completed the survey; most were women (72%), and
      almost half (48%) were nurses. Sixty-seven percent of them had ever received
      training related to BPE management; 62% perceived themselves to be at high risk
      for BPE. Among the 426 HCWs who were exposed to sharps injuries or splashes in
      the last 6 months, 160 (37%) reported the exposure. Of these, 111 of the 160
      (69%) received PEP, and 79 of the 111 (71%) completed their medication. Whereas
      >92% of the total HCWs had ever been tested for HIV, only 557 (37%) were tested
      in their own health facility. Most HCWs (87%, n = 1,406) reported they would be
      interested in testing themselves. Of HCWs who reported an exposure, less than
      half (49%, n = 78) were satisfied with existing reporting systems. CONCLUSIONS:
      Underreporting of occupational exposures and dissatisfaction with PEP management
      is common among HCWs. Improved PEP management strategies and regular monitoring
      are needed.

PMID- 27021511
TI  - Observed infection control compliance in a dental school: A natural experiment.
AB  - OBJECTIVE: The objective of this study was to determine student adherence to
      infection control policies at 1 dental school. A secondary objective was to
      determine the influence of Ebola virus disease (EVD)-related training on student
      infection control behaviors. METHODS: An instrument to assess and record
      infection control behaviors was developed to reflect Centers for Disease Control
      and Prevention guidelines as well as current teaching. Third- and fourth-year
      dental students were observed during patient-care appointments and behaviors were
      recorded and analyzed. Behaviors observed before the EVD outbreak and subsequent
      mandatory in-service training were compared with behaviors observed after
      completion of the training. RESULTS: Use of personal protective equipment was
      nearly universal. Overall compliance with infection control parameters was 88%.
      However, only a minority of students demonstrated no breaches of protocol. Most
      violations involved improper mask use and improper glove use during the
      intraoperative phase of an appointment and failure to wash hands after removing
      gloves. There were no significant overall differences in observed behavior pre-
      and post-EVD training. CONCLUSION: Overall compliance with recommendations was
      high but some areas showed room for improvement. Future training in infection
      control should focus on these areas. Training related to EVD had no influence on
      student behavior.

PMID- 27021512
TI  - Hospital air: A potential route for transmission of infections caused by beta
      lactam-resistant bacteria.
AB  - BACKGROUND: The emergence of bacterial resistance to beta-lactam antibiotics
      seriously challenges the treatment of various nosocomial infections. This study
      was designed to investigate the presence of beta-lactam-resistant bacteria (BLRB)
      in hospital air. METHODS: A total of 64 air samples were collected in 4 hospital
      wards. Detection of airborne bacteria was carried out using culture plates with
      and without beta-lactams. BLRB isolates were screened for the presence of 5
      common beta-lactamase-encoding genes. Sequence analysis of predominant BLRB was
      also performed. RESULTS: The prevalence of BLRB ranged between 3% and 34%.
      Oxacillin-resistant bacteria had the highest prevalence, followed by ceftazidime-
      and cefazolin-resistant bacteria. The frequency of beta-lactamase-encoding genes
      in isolated BLRB ranged between 0% and 47%, with the highest and lowest detection
      for OXA-23 and CTX-m-32, respectively. MecA had a relatively high frequency in
      surgery wards and operating theaters, whereas the frequency of blaTEM was higher
      in intensive care units and internal medicine wards. OXA-51 was detected in 4
      wards. Acinetobacter spp, Acinetobacter baumannii, and Staphylococcus spp were
      the most predominant BLRB. CONCLUSIONS: The results revealed that hospital air is
      a potential route of transmission of BLRB, such as Acinetobacter and
      Staphylococcus, 2 important causative agents of nosocomial infections. Therefore,
      improvement of control measures against the spreading of airborne bacteria in
      hospital environments is warranted.

PMID- 27021513
TI  - Adjuvant materials that enhance bovine gammadelta T cell responses.
AB  - Despite the availability of vaccines and antibiotics, viral, bacterial and
      parasite-induced intestinal and pulmonary diseases still cause significant losses
      to the livestock industry. Excepting improvements in calf survival due to
      predation, there have been only modest improvements in bovine calf survival since
      1991. Strikingly, digestive and respiratory diseases still account for almost
      half of the non-predator deaths in calves. The innate immune system has evolved
      to rapidly recognize and respond to invasive microbial threats. Augmentation of
      innate immunity is a broad-spectrum, potent and non-specific alternative approach
      to effectively counter a microbial invasion. In recent years we have focused our
      research efforts on the development of effective and inexpensive adjuvant
      therapies for cattle that can be used to help mitigate infection. Unique in our
      approach to the development of the potential new treatments, is our focus on
      bovine gammadelta T cells, which are important lymphocytes of the innate immune
      system and of particular importance to ruminant immunological health. This review
      focuses on recent results obtained using two such adjuvant materials.

PMID- 27021514
TI  - Alterations in Resting-State Functional Connectivity Link Mindfulness Meditation
      With Reduced Interleukin-6: A Randomized Controlled Trial.
AB  - BACKGROUND: Mindfulness meditation training interventions have been shown to
      improve markers of health, but the underlying neurobiological mechanisms are not
      known. Building on initial cross-sectional research showing that mindfulness
      meditation may increase default mode network (DMN) resting-state functional
      connectivity (rsFC) with regions important in top-down executive control
      (dorsolateral prefrontal cortex [dlPFC]), here we test whether mindfulness
      meditation training increases DMN-dlPFC rsFC and whether these rsFC alterations
      prospectively explain improvements in interleukin (IL)-6 in a randomized
      controlled trial. METHODS: Stressed job-seeking unemployed community adults (n =
      35) were randomized to either a 3-day intensive residential mindfulness
      meditation or relaxation training program. Participants completed a 5-minute
      resting-state scan before and after the intervention program. Participants also
      provided blood samples at preintervention and at 4-month follow-up, which were
      assayed for circulating IL-6, a biomarker of systemic inflammation. RESULTS: We
      tested for alterations in DMN rsFC using a posterior cingulate cortex seed-based
      analysis and found that mindfulness meditation training, and not relaxation
      training, increased posterior cingulate cortex rsFC with left dlPFC (p < .05,
      corrected). These pretraining to posttraining alterations in posterior cingulate
      cortex-dlPFC rsFC statistically mediated mindfulness meditation training
      improvements in IL-6 at 4-month follow-up. Specifically, these alterations in
      rsFC statistically explained 30% of the overall mindfulness meditation training
      effects on IL-6 at follow-up. CONCLUSIONS: These findings provide the first
      evidence that mindfulness meditation training functionally couples the DMN with a
      region known to be important in top-down executive control at rest (left dlPFC),
      which, in turn, is associated with improvements in a marker of inflammatory
      disease risk.

PMID- 27021516
TI  - Desensitization with plasma exchange in a patient with human leukocyte antigen
      donor-specific antibodies before T-cell-replete haploidentical transplantation.
AB  - BACKGROUND: The presence of human leukocyte antigen donor-specific antibodies
      (DSAs) increases the risk of graft failure in T-cell-replete haploidentical
      hematopoietic stem cell transplantation (haplo-HSCT) CASE REPORT: A 49-year-old
      female with high-risk acute myeloid leukemia in first complete remission received
      a haplo-HSCT from her daughter. Pretransplant recipient screening examination
      showed high DSAs levels against unshared class I leukocyte antigens. RESULTS: The
      patient underwent a desensitization program consisting of plasma exchange (PEX),
      polyvalent intravenous (IV) immunoglobulins, and IV tacrolimus and mycophenolate
      mofetil (MMF). This protocol resulted in the disappearance of the DSA anti HLA
      B41. Engraftment was prompt with stable full donor chimerism. CONCLUSIONS: This
      case report suggests that the adopted scheme is safe for reducing DSA levels and
      facilitating donor engraftment in patients scheduled for haplo-HSCT.

PMID- 27021515
TI  - miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric
      carcinoma.
AB  - Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently
      reduced in a variety of tumors, including gastric cancer. Previous findings have
      indicated that PDCD4 participates in tumorigenesis through the regulation of
      apoptosis, but the molecular basis of this process has not been fully elucidated,
      and no studies have shown the upstream regulation of this gene in gastric cancer.
      In this study, we used bioinformatics analysis to search for miRNAs that could
      potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we
      observed the inverse correlation between miR-93 and PDCD4 protein levels, but not
      mRNA levels, in human gastric cancer tissues. We further experimentally validated
      PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric
      cancer cells after the overexpression or knockdown of miR-93. Additionally, the
      biological consequences of targeting PDCD4 through miR-93 were examined using
      cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4
      through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we
      revealed that miR-93 promoted the development of gastric tumor growth in
      xenograft mice by negatively regulating PDCD4. Taken together, the findings of
      the present study indicated the oncogenic role of miR-93 in gastric cancer
      tumorigenesis through targeting PDCD4, particularly in apoptosis. 

PMID- 27021517
TI  - Ablation of cardiac myosin binding protein-C disrupts the super-relaxed state of
      myosin in murine cardiomyocytes.
AB  - Cardiac myosin binding protein-C (cMyBP-C) is a structural and regulatory
      component of cardiac thick filaments. It is observed in electron micrographs as
      seven to nine transverse stripes in the central portion of each half of the A
      band. Its C-terminus binds tightly to the myosin rod and contributes to thick
      filament structure, while the N-terminus can bind both myosin S2 and actin,
      influencing their structure and function. Mutations in the MYBPC3 gene (encoding
      cMyBP-C) are commonly associated with hypertrophic cardiomyopathy (HCM). In
      cardiac cells there exists a population of myosin heads in the super-relaxed
      (SRX) state, which are bound to the thick filament core with a highly inhibited
      ATPase activity. This report examines the role cMyBP-C plays in regulating the
      population of the SRX state of cardiac myosin by using an assay that measures
      single ATP turnover of myosin. We report a significant decrease in the proportion
      of myosin heads in the SRX state in homozygous cMyBP-C knockout mice, however
      heterozygous cMyBP-C knockout mice do not significantly differ from the wild
      type. A smaller, non-significant decrease is observed when thoracic aortic
      constriction is used to induce cardiac hypertrophy in mutation negative mice.
      These results support the proposal that cMyBP-C stabilises the thick filament and
      that the loss of cMyBP-C results in an untethering of myosin heads. This results
      in an increased myosin ATP turnover, further consolidating the relationship
      between thick filament structure and the myosin ATPase.

PMID- 27021518
TI  - Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic
      cardiomyopathy: Role of fibrosis and connexin remodelling.
AB  - Conduction abnormalities are frequently associated with cardiac disease, though
      the mechanisms underlying the commonly associated increases in PQ interval are
      not known. This study uses a chronic left ventricular (LV) apex myocardial
      infarction (MI) model in the rabbit to create significant left ventricular
      dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ
      interval increases by approximately 7ms (10%) with no significant change in
      average heart rate. Optical mapping of isolated Langendorff perfused rabbit
      hearts recapitulated this result: time to earliest activation of the LV was
      increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural
      conduction times were not altered in the LVD group. Isolated AVN preparations
      from the LVD group demonstrated a significantly longer conduction time (by
      approximately 20ms) between atrial and His electrograms than sham controls across
      a range of pacing cycle lengths. This difference was accompanied by increased
      effective refractory period and Wenckebach cycle length, suggesting significantly
      altered AVN electrophysiology post-MI. The AVN origin of abnormality was further
      highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN
      preparations revealed increased fibrosis and gap junction protein (connexin43 and
      40) remodelling in the AVN of LVD animals compared to sham. A significant
      increase in myocyte-non-myocyte connexin co-localization was also observed after
      LVD. These changes may increase the electrotonic load experienced by AVN muscle
      cells and contribute to slowed conduction velocity within the AVN.

PMID- 27021519
TI  - Receptor-mediated mitophagy.
AB  - Mitochondria are essential organelles that supply ATP through oxidative
      phosphorylation to maintain cellular homeostasis. Extrinsic or intrinsic agents
      can impair mitochondria, and these impaired mitochondria can generate reactive
      oxygen species (ROS) as byproducts, inducing cellular damage and cell death. The
      quality control of mitochondria is essential for the maintenance of normal
      cellular functions, particularly in cardiomyocytes, because they are terminally
      differentiated. Accumulation of damaged mitochondria is characteristic of various
      diseases, including heart failure, neurodegenerative disease, and aging-related
      diseases. Mitochondria are generally degraded through autophagy, an intracellular
      degradation system that is conserved from yeast to mammals. Autophagy is thought
      to be a nonselective degradation process in which cytoplasmic proteins and
      organelles are engulfed by isolation membrane to form autophagosomes in
      eukaryotic cells. However, recent studies have described the process of selective
      autophagy, which targets specific proteins or organelles such as mitochondria.
      Mitochondria-specific autophagy is called mitophagy. Dysregulation of mitophagy
      is implicated in the development of chronic diseases including neurodegenerative
      diseases, metabolic diseases, and heart failure. In this review, we discuss
      recent progress in research on mitophagy receptors.

PMID- 27021520
TI  - "Got mentorship?".

PMID- 27021521
TI  - Potentially functional polymorphisms in the LIN28B gene contribute to
      neuroblastoma susceptibility in Chinese children.
AB  - Neuroblastoma is the most commonly diagnosed solid tumour outside the central
      nervous system in children. However, genetic factors underlying neuroblastoma
      remain largely unclear. Previous genome-wide association study indicated that lin
      28 homolog B (LIN28B) might play an important role in the development of
      neuroblastoma and also contributed to its poor overall survival. With the purpose
      to evaluate the association between LIN28B gene polymorphisms and neuroblastoma
      susceptibility in Southern Chinese population, we conducted this study with 256
      neuroblastoma cases and 531 cancer-free controls. Four potentially functional
      polymorphisms (rs221634 A>T, rs221635 T>C, rs314276 C>A and rs9404590 T>G) were
      genotyped using Taqman method. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated to assess the associations between the selected single
      nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We also
      performed genotype-phenotype association analysis to explore the effects of the
      selected SNPs on LIN28B gene transcripts. Our results indicated that the rs221634
      TT genotype was associated with an increased neuroblastoma risk (TT versus AA/AT:
      adjusted OR = 1.50, 95% CI = 1.04-2.17). The association was more pronounced in
      males, patients with tumour of mediastinum origin, as well as patients in early
      clinical stages. Moreover, overall analysis and stratified analysis also showed
      an increased risk of neuroblastoma for carrier of the 2-4 risk genotypes. In
      summary, these results indicated that the LIN28B rs221634 A>T polymorphism was
      associated with an increased neuroblastoma risk in Southern Chinese children.
      These findings need further validation in large studies with different
      ethnicities involved.

PMID- 27021522
TI  - An Exploratory Study on the Pathways of Cr (VI) Reduction in Sulfate-reducing Up
      flow Anaerobic Sludge Bed (UASB) Reactor.
AB  - Electroplating wastewater contains both Cr (VI) and sulfate. So Cr (VI) removal
      under sulfate-rich condition is quite complicated. This study mainly investigates
      the pathways for Cr (VI) removal under biological sulfate-reducing condition in
      the up-flow anaerobic sludge bed (UASB) reactor. Two potential pathways are found
      for the removal of Cr (VI). The first one is the sulfidogenesis-induced Cr (VI)
      reduction pathway (for 90% Cr (VI) removal), in which Cr (VI) is reduced by
      sulfide generated from biological reduction of sulfate. The second one leads to
      direct reduction of Cr (VI) which is utilized by bacteria as the electron
      acceptor (for 10% Cr (VI) removal). Batch test results confirmed that sulfide was
      oxidized to elemental sulfur instead of sulfate during Cr (VI) reduction. The
      produced extracellular polymeric substances (EPS) provided protection to the
      microbes, resulting in effective removal of Cr (VI). Sulfate-reducing bacteria
      (SRB) genera accounted for 11.1% of the total bacterial community; thus they
      could be the major organisms mediating the sulfidogenesis-induced reduction of Cr
      (VI). In addition, chromate-utilizing genera (e.g. Microbacterium) were also
      detected, which were possibly responsible for the direct reduction of Cr (VI)
      using organics as the electron donor and Cr (VI) as the electron acceptor. 

PMID- 27021523
TI  - Wolbachia pipientis should not be split into multiple species: A response to
      Ramirez-Puebla et al., "Species in Wolbachia? Proposal for the designation of
      'Candidatus Wolbachia bourtzisii', 'Candidatus Wolbachia onchocercicola',
      'Candidatus Wolbachia blaxteri', 'Candidatus Wolbachia brugii', 'Candidatus
      Wolbachia taylori', 'Candidatus Wolbachia collembolicola' and 'Candidatus
      Wolbachia multihospitum' for the different species within Wolbachia supergroups".

PMID- 27021524
TI  - High-resolution subtyping of Staphylococcus aureus strains by means of Fourier
      transform infrared spectroscopy.
AB  - Staphylococcus aureus causes a variety of serious illnesses in humans and
      animals. Subtyping of S. aureus isolates plays a crucial role in epidemiological
      investigations. Metabolic fingerprinting by Fourier-transform infrared (FTIR)
      spectroscopy is commonly used to identify microbes at species as well as
      subspecies level. In this study, we aimed to assess the suitability of FTIR
      spectroscopy as a tool for S. aureus subtyping. To this end, we compared the
      subtyping performance of FTIR spectroscopy to other subtyping methods such as
      pulsed field gel electrophoresis (PFGE) and spa typing in a blinded experimental
      setup and investigated the ability of FTIR spectroscopy for identifying S. aureus
      clonal complexes (CC). A total of 70 S. aureus strains from human, animal, and
      food sources were selected, for which clonal complexes and a unique virulence and
      resistance gene pattern had been determined by DNA microarray analysis. FTIR
      spectral analysis resulted in high discriminatory power similar as obtained by
      spa typing and PFGE. High directional concordance was found between FTIR
      spectroscopy based subtypes and capsular polysaccharide expression detected by
      FTIR spectroscopy and the cap specific locus, reflecting strain specific
      expression of capsular polysaccharides and/or other surface glycopolymers, such
      as wall teichoic acid, peptidoglycane, and lipoteichoic acid. Supervised
      chemometrics showed only limited possibilities for differentiation of S. aureus
      CC by FTIR spectroscopy with the exception of CC45 and CC705. In conclusion, FTIR
      spectroscopy represents a valuable tool for S. aureus subtyping, which
      complements current molecular and proteomic strain typing. 

PMID- 27021525
TI  - Thermoelectric properties of PEDOT nanowire/PEDOT hybrids.
AB  - Freestanding poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires were synthesized
      by template-confined in situ polymerization, and then integrated into polystyrene
      sulfonate (PSS)-doped PEDOT and tosylate-doped PEDOT hosts, respectively. The
      hybrid morphologies were characterized by atomic force microscopy, indicating the
      homogeneous dispersion of PEDOT nanowires. The thermoelectric properties of the
      resultant hybrids were measured, and the power factor was found to be enhanced by
      9-fold in comparison with PEDOT: PSS mixed with 5 vol% dimethyl sulfoxide while
      the low thermal conductivity was still maintained. Such a significant improvement
      could be attributed to the synergistic effects of interfacial energy filtering,
      component contributions, and changes of carrier concentrations in the host
      materials. Upon addition of 0.2 wt% PEDOT nanowires, the resultant composites
      demonstrated a power factor as high as 446.6 MUW m(-1) K(-2) and the
      thermoelectric figure of merit could reach 0.44 at room temperature. The
      thermoelectric devices were investigated by using the PEDOT nanowire/PEDOT hybrid
      as a p-type leg and nitrogen-doped graphene as an n-type leg. The normalized
      power output was as high as ~0.5 mW m(-2) for a temperature gradient of DeltaT =
      10.1  degrees C, indicating great potential for practical applications. These
      findings open up a new route towards high-performance organic thermoelectric
      materials and devices.

PMID- 27021526
TI  - Systematic Review of Factors Influencing Farmers' Market Use Overall and among
      Low-Income Populations.
AB  - BACKGROUND: Recent evidence indicates a widening gap in fruit and vegetable (F/V)
      consumption between high- and low-income Americans. This gap is related, in part,
      to decreased access to food retailers that sell fresh F/V in low-income
      communities. Farmers' markets are identified as a strategy for improving F/V
      consumption by increasing access to these foods. OBJECTIVES: The aim of this
      systematic review was to examine literature published from 1994 to 2014 to
      identify facilitators and barriers of farmers' markets use, particularly among
      low-income consumers. DESIGN: Peer-reviewed literature was identified in Ebsco
      Host (Academic Search Complete). Inclusion criteria for abstract review was
      primary research focused on farmers' market use identifying 87 studies for full
      text review. Full-text review identified articles focused on facilitators and/or
      barriers of farmers' market use resulting in 49 articles. At least two reviewers
      completed review of all articles. RESULTS: Of the 49 articles, 39% specified
      inclusion of low-income consumers and fewer than 15% focused on racial and ethnic
      minorities. Few studies were guided by theory and/or used standardized metrics.
      Results indicate farmers' market use is influenced by multiple economic, service
      delivery, spatial-temporal, social, and personal factors. Among studies that
      included low-income populations (n=19), key barriers to farmers' market use were
      perceptions that food assistance benefits were not accepted, belief that food
      variety at farmers' markets was limited, lack of access to transportation, lack
      of racial/ethnic diversity in the market space, and mismatch between markets and
      personal lifestyles. There is wide variation in study design and reporting
      standards and infrequent use of standardized measures limiting comparisons across
      studies. CONCLUSIONS: There is a need to establish valid and reliable metrics and
      reporting standards for evaluating farmers' markets. Findings may inform
      interventions, programs, and policies to promote farmers' market use.

PMID- 27021527
TI  - Photolysis-driven merging of microdroplets in microfluidic chambers.
AB  - Photolysis of microdroplets, stabilized by aminoquinoline-derived photosensitive
      surfactants composed of polyethyleneglycol/perfluorinated polyether (PEG/PFPE)
      diblock amphiphiles by using 355 nm ps pulsed laser light, resulted in rapid
      controlled coalescence of targeted microdroplets offering the prospect of a novel
      type of droplet merging with high stereospatial integrity for microfluidic
      systems. 

PMID- 27021529
TI  - Corrigendum.

PMID- 27021528
TI  - Overexpression of alpha1 chain of type XI collagen (COL11A1) aids in the
      diagnosis of invasive carcinoma in endoscopically removed malignant colorectal
      polyps.
AB  - INTRODUCTION: The histologic distinction between benign misplaced adenomatous
      mucosa and invasive adenocarcinoma in colorectal polyps can be challenging. The
      alpha1 chain of type XI collagen (COL11A1) has been shown to be overexpressed in
      cancer-associated stromal fibroblasts. The aim of this study was to investigate
      the operating characteristics of COL11A1 immunostaining in benign and malignant
      colorectal polyps as a potential diagnostic aid. MATERIALS AND METHODS: Sixty-six
      endoscopically-removed paraffin-embedded colorectal polyps were stained with anti
      COL11A1 antibody. They comprised 50 malignant polyps (MPs) with invasive
      adenocarcinoma (including 5 with concurrent benign misplaced adenomatous mucosa)
      and 16 adenomas, 11 with and 5 without benign misplaced adenomatous mucosa.
      RESULTS: COL11A1 was expressed either diffusely or focally in cancer-associated
      desmoplastic fibroblasts in 72.0% (36/50) of MPs. The rates of COL11A1 expression
      and the immunohistochemical staining patterns of the COL11A1 were positively
      correlated with the depth of cancer invasion in MPs. COL11A1 was expressed in all
      9 (100%) MPs with a mucinous component and in 16/18 (88.9%) MPs associated with
      significant electrocautery effects. COL11A1 was not expressed adjacent to
      conventional adenomas or in the stroma adjacent to misplaced adenomatous mucosa.
      CONCLUSIONS: COL11A1 antibody can assist in distinguishing the cancer-associated
      desmoplastic stroma from that associated with misplaced adenomatous mucosa. It is
      particularly helpful when electrocautery artifacts or mucin pools interfere with
      the diagnosis of invasive carcinoma. However, COL11A1 has limited value in
      diagnosing superfically invasive carcinomas with very little desmoplastic stroma
      due to its low positive rate and focal expression in some cases.

PMID- 27021530
TI  - Plasmid-mediated resistance and virulence mechanisms in the private health sector
      in KwaZulu-Natal, South Africa: An investigation of methicillin resistant
      Staphylococcus aureus (MRSA) clinical isolates collected during a three month
      period.
AB  - OBJECTIVES: Due to the lack of information on the plasmid content of MRSA strains
      in South Africa (SA), this study investigated the resistance and virulence
      mechanisms of 27 clinical isolates from the private health care sector over a
      period of 3 months. METHODS: Plasmids were extracted and the presence of MRSA
      confirmed by the presence of mecA. The isolates were subjected to antimicrobial
      susceptibility testing and molecular characterization of common resistance
      encoding genes and frequently encountered virulence factors by PCR using plasmid
      DNA as the template. The genetic relatedness between the isolates was determined
      by pulsed field gel electrophoresis (PFGE). RESULTS: All isolates were plasmid
      positive, and displayed ampillicin, ciprofloxacin, gentamicin, rifampicin,
      tetracycline, erythromycin, and clindamycin resistance. They were all fully
      susceptible to daptomycin, linezolid, vancomycin, tigecycline and fusidic acid.
      Multidrug resistance (MDR) was found in 74.1% (20/27) of the MRSA isolates. The
      frequency of the resistance and virulence genes ranged from 100% to 0%. PFGE
      analysis revealed 10 pulsotypes, designated A-J, which showed correlation with
      resistance profile of the isolates in each group. Of note, 85.2% (23/27) of the
      isolates clustered into six major PFGE types giving an indication of similar
      circulating MRSA clones. CONCLUSIONS: This study highlights the genetic diversity
      and resistance mechanisms in MRSA strains from the private health sector in SA
      hence the need for implementing effective infection control programs.

PMID- 27021531
TI  - Application of Pharmacodynamic Profiling for the Selection of Optimal beta-lactam
      Regimens in a Large University Hospital.
AB  - BACKGROUND: Infections caused by drug-resistant Gram-negative bacteria (GNB) are
      increasing worldwide and as a result, the selection of appropriate empiric
      antibiotics (ATBs) has been made increasingly difficult. The present study aimed
      to identify optimized dosing regimens of intravenous (IV) ATBs, defined by
      cumulative fraction response (CFR), against E. coli (EC), K. pneumoniae (KP), P.
      aeruginosa (PA), and A. baumannii (AB) at 2,300-bed University Hospital.
      MATERIALS AND METHODS: The minimum inhibitory concentrations (MIC) of EC, KP, PA,
      and AB from clinical specimens, 250 each, were determined. Pharmacodynamic
      profiling using Monte Carlo Simulation was performed for standard, high dosage,
      and prolonged infusions (PI) of ceftriaxone, cefepime, ceftazidime, imipenem,
      meropenem, and doripenem. A CFR of >=90% was targeted as providing a sufficiently
      high ATB exposure. RESULTS: When considering the Enterobacteriaceae, the %
      susceptible for the cephalosporins ranged from 60% for ceftriaxone to 86% for
      cefepime, as a result only the 2g q8h regimens of ceftazidime and cefepime
      provided high CFRs. In contrast, all the carbapenems had % susceptible and CFRs
      >=90% for EC and KP. While cefepime and ceftazidime demonstrated higher %
      susceptibility (82-83%) for PA relative to that of the carbapenems (61-69%) only
      doripenem 2g q8h (4h PI) achieved an optimal CFR (92%) against this organism. Due
      to the MIC profiles and dismal susceptibilities of AB (16-22%), none of the
      regimens studied achieved CFRs > 65%. CONCLUSIONS: The pharmacodynamic profiling
      undertaken in the current study provides insights that allow prescribers to
      select more appropriate empirical antibiotic regimens for the treatment of
      infection caused by these common GNB pathogens at this Thai hospital. While
      higher doses and PI of beta-lactams improve exposures against EC, KP and PA, this
      approach will not sufficiently enhance their potency against AB, thus alternative
      therapies should be considered for this organism.

PMID- 27021532
TI  - Pneumocystis pneumonia suspected cases in 604 non-HIV and HIV patients.
AB  - BACKGROUND: Pneumocystis pneumonia (PCP) is one of the most devastating fungal
      diseases in patients with impaired immunity. Effective antiviral therapies have
      reduced the burden of PCP among AIDS patients, but an increase in the prevalence
      of this disease among persons receiving immunosuppressive therapies has been
      reported. METHODS: We retrospectively reviewed HIV and non-HIV PCP patients
      diagnosed in our department during a nine year period. Data were collected from
      the local database completed during the diagnosis procedure. For each patient,
      demographic, clinical, radiological, biological and therapeutic data were
      analyzed. RESULTS: A total of 21,274 bronchoalveolar samples were received from
      patients suspected of pneumocystosis during the study period, leading to a
      discharge diagnosis of PCP for 604 patients (143 HIV-positive and 461 HIV
      negative). The ratio of non-HIV versus HIV patients presenting PCP increased from
      1.7 to 5.6 during the study period. The mortality rate at day 14 was 16%,
      occurring mostly in non-HIV patients (20.6% compared to 1.4%, P<0.0001), while
      non-HIV patients were less symptomatic at diagnosis than AIDS patients.
      CONCLUSIONS: This study presents one of the higher number of HIV and non-HIV
      patients presenting with PCP in a single center. Pneumocystosis is now a crucial
      health challenge for patients receiving immunosuppressive therapy, with a high
      mortality rate. This study highlights the need for international guidelines for
      prophylaxis of PCP in non-HIV patients.

PMID- 27021533
TI  - The effect of type 2 diabetes mellitus and smoking on periodontal parameters and
      salivary matrix metalloproteinase-8 levels.
AB  - The present study was carried out to evaluate the effect of type 2 diabetes
      mellitus (DM) and smoking on periodontal parameters and on the levels of salivary
      matrix metalloproteinase (MMP-8). One hundred and twenty five subjects were
      divided into five groups: group 1, systemically and periodontally healthy
      subjects (n = 25); group 2, systemically healthy subjects but with chronic
      periodontitis (n = 25); group 3, subjects with type 2 DM and chronic
      periodontitis (n = 25); group 4, smokers with chronic periodontitis (n = 25);
      group 5, diabetic-smokers with chronic periodontitis (n = 25). MMP-8 level in
      saliva was estimated by enzyme linked immunosorbent assay (ELISA) using
      Quantikine human total MMP-8 immunoassay kit. The result showed that the clinical
      periodontal parameters and the mean levels of the salivary MMP-8 were
      significantly higher for diabetic-smokers than other study groups. A highly
      significant positive correlation (r) between MMP-8 and periodontal parameters was
      also observed in diabetic-smoker patients. The findings suggest that diabetic
      smokers have increased periodontal breakdown and are associated with an increased
      extent and severity of periodontitis. (J Oral Sci 58, 1-6, 2016). 

PMID- 27021534
TI  - Prevalence and characteristics of orofacial pain in university students.
AB  - This cross-sectional study investigated the characteristics and prevalence of
      orofacial pain, and its associations with sociodemographic characteristics, in
      319 university students: 188 second-year students in the Medical Faculty and 131
      students in the Faculty of Technical Sciences at the University of Kosovska
      Mitrovica. A specially designed questionnaire was used to assess the prevalence
      and characteristics of pain. Among the 319 students, 101 (32%) reported previous
      orofacial pain, and pain was more frequent among women (P < 0.05). Logistic
      regression revealed that gender was an important predictor of pain and that the
      risk for pain development among women was 1.8 times that among men. Place of
      residence and relationship status were not associated with frequency of orofacial
      pain. The regions with the highest pain prevalences were the temporal region (7%;
      95% confidence interval, 4-10%) and the region around the eye (6%; 95% confidence
      interval, 4-9%). The first episode of orofacial pain was less than 3 months
      previously in 59% of the participants, and 39% of students had sought
      professional medical help. (J Oral Sci 58, 7-13, 2016). 

PMID- 27021535
TI  - Degree of conversion and leached monomers of urethane dimethacrylate
      hydroxypropyl methacrylate-based dental resin systems.
AB  - The degree of conversion (DC) and monomer leaching of three experimental urethane
      dimethacrylate (UEDMA)-hydroxypropyl methacrylate (HPMA)-based resin systems were
      studied. Three experimental resins (E1: 70.6 wt% UEDMA + 27.4 wt% HPMA, E2: 80.6
      wt% UEDMA + 17.4 wt% HPMA, E3: 90.6 wt% UEDMA + 7.4 wt% HPMA) and one control
      resin [C: 70.6 wt% bis-phenol A glycidyl methacrylate (bis-GMA) + 27.4 wt% methyl
      methacrylate (MMA)] were prepared. For the DC test, cylindrical specimens [1.5 mm
      (h) * 6 mm (d)] were scanned with an ATR-FTIR instrument before and after light
      curing (n = 5). For the monomer leaching test, block-shaped specimens [5.67 mm
      (l) * 2.00 mm (w) * 2.00 mm (h)] were light-cured (n = 6), stored in a 75%
      ethanol:water solution for 3 days, and then analyzed with HPLC. The UEDMA-HPMA
      based experimental groups showed higher DC (62-78%) than the bis-GMA-MMA-based
      control group (58-66%), and the DC decreased as the UEDMA content increased (P <
      0.05). Amongst the four groups, E3 exhibited the lowest leaching of both mono
      methacrylate (0.1% HPMA) and dimethacrylate (<0.043% UEDMA) monomers after 30 or
      40 s of curing. The UEDMA-HPMA-based resins, therefore, exhibited higher DC and
      less monomer leaching compared to the bis-GMA-MMA-based resin. (J Oral Sci 58, 15
      22, 2016). 

PMID- 27021536
TI  - Efficacy and complications of submental tracheal intubation compared with
      tracheostomy in maxillofacial trauma patients.
AB  - Submental tracheal intubation is a technique for use in patients with
      maxillofacial trauma. The purpose of this retrospective study was to evaluate the
      efficacy and complications of this technique compared with tracheostomy. Twenty
      five patients underwent submental tracheal intubation since 2001. Submental
      tracheal intubation was performed in cases needing intermaxillary fixation
      complicated by a nasal pyramid or anterior skull base fracture. No severe
      perioperative or long-term complications were noted. Intra- and postoperative
      complications were observed in three patients. In one case, the tube was
      accidentally dislodged into the right main bronchus during submental tracheal
      intubation. Two patients developed skin infections. Submental scarring was
      undetectable, except for one patient with slight scarring. Submental tracheal
      intubation avoids the complications associated with tracheostomy and the
      difficulty of nasal intubation during intubation and surgery. Therefore,
      submental tracheal intubation is useful in the intraoperative management of
      patients with complex maxillofacial trauma. (J Oral Sci 58, 23-28, 2016). 

PMID- 27021537
TI  - Retrospective magnetic resonance imaging study of risk factors associated with
      sideways disk displacement of the temporomandibular joint.
AB  - As part of our ongoing investigation of risk and predictive factors associated
      with temporomandibular disorders, we used magnetic resonance imaging (MRI) to
      identify risk factors for sideways disk displacement of the temporomandibular
      joint in 26 patients with MRI-confirmed unilateral pure sideways disk
      displacement (medial or lateral disk displacement) and normal positioning of the
      contralateral temporomandibular joint. Coronal morphologic harmonization between
      the condyle and fossa, angle between the axis of the ramus and condyle, and angle
      between the lateral pterygoid muscle (LPM) and condyle were evaluated. Only angle
      of the LPM related to the condyle was significantly correlated with mediolateral
      disk position; the angles of joints with medial, normal, and lateral disk
      positions were 70.2 degrees , 66.7 degrees , and 60.1 degrees , respectively.
      These results suggest that a greater angle of the inferior head of the LPM to the
      axis of the condyle on axial MRI images may cause medial disk displacement, while
      a smaller angle may result in lateral disk displacement. (J Oral Sci 58, 29-34,
      2016). 

PMID- 27021538
TI  - Effects of chlorhexidine (gel) application on bacterial levels and orthodontic
      brackets during orthodontic treatment.
AB  - The objectives of this study were to evaluate the effects of applying 0.50%
      chlorhexidine (CHX) gel using the dental drug delivery system (3DS) on salivary
      Streptococcus mutans (S. mutans) and on the surface topography of metal and
      ceramic orthodontic brackets. The study involved 20 orthodontic patients with
      high levels of salivary S. mutans. The patients were treated with professional
      mechanical tooth cleaning followed by application of 0.50% CHX using individual
      trays (3DS). Salivary S. mutans levels were repeatedly measured 1, 2, 4, and 8
      weeks post-treatment. In vitro study utilized forty ceramic and metallic brackets
      that were immersed in 0.50% CHX gel for 10 min, whereas another untreated forty
      brackets served as controls. The frictional resistances of stainless steel wires
      to the brackets before and after CHX treatment were recorded using a universal
      testing machine. Scanning electron microscopy was used to compare changes in the
      surface topography of brackets. Statistical analyses were used to determine the
      effect of CHX on bacterial count and to evaluate the effect of CHX on frictional
      resistance. According to the results of this study, S. mutans levels were reduced
      significantly (P < 0.05). There were no significant changes in the frictional
      resistance and surface topography of brackets before or after application of CHX.
      (J Oral Sci 58, 35-42, 2016). 

PMID- 27021539
TI  - Clinical profile of 108 cases of oral lichen planus.
AB  - Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disease with a
      varied clinical presentation. The present clinical study was carried out to
      clarify the demographic and clinical profile of 108 patients with OLP. The
      patients were identified based on the diagnostic criteria proposed by van der
      Meij et al. (2003) modified from the WHO (1978) clinical and histopathologic
      definition of OLP. Information such as age, gender, clinical presentation and
      type of OLP, site of involvement, symptoms, extraoral involvement, history of
      systemic disease, familial occurrence and risk factors like chewing and smoking
      tobacco, chewing betel quid, alcohol consumption were obtained. Mean age of OLP
      patients was 45.4 years, and among the identified patients, 70.4% were females.
      The most frequent clinical type was the reticular form (80.6%). The OLP lesions
      were symptomatic in 77.8% of the patients. The buccal mucosa was the most
      affected site (87.9%) and multiple oral lesions were observed in 41.7% of the
      patients. Among the OLP patients, 36.1% and 4.7% reported chewing tobacco and
      smoking tobacco, respectively. Histopathologically, epithelial dysplasia was seen
      in two cases. The chronic nature of OLP warrants patient education, psychological
      support and long-term follow up. (J Oral Sci 58, 43-47, 2016). 

PMID- 27021540
TI  - A 36-month follow-up prospective cohort study on peri-implant bone loss of Morse
      Taper connection implants with platform switching.
AB  - A prospective cohort study was designed to measure marginal bone level changes at
      36-month follow-up and to evaluate the influence of biologically relevant,
      anatomic and stress-related variables. STROBE guidelines were followed. Totally,
      748 implants were inserted into 350 patients. Standardized periapical radiographs
      were taken at 2- (stage-two surgery), 12-, 24-, and 36-month follow-ups.
      Descriptive statistics were used and inter- and intra-examiner reliability were
      determined. A mixed-model was used to evaluate predictor variables. Statistical
      analysis was performed at implant level (statistical significance: P < 0.05). A
      total of 34 (4.5%) implants failed; of the 34 implants, 6 were early failures
      (0.8%) and 28 were late failures (3.7%). A total of 576 implants reached 36-month
      follow-up (mean follow-up: 25.58 months; SD: 10.32). Mean marginal bone
      remodeling was -0.56 mm. (SD: 1.30; range: -6.80 +/- 3.65). A statistically
      significant, higher marginal bone loss was found for subcrestal implants and
      subcrestal implants inserted into the maxilla, for implants inserted into
      patients aged over 50 years, and for early-delayed implants inserted into
      patients aged over 50 years. In conclusion, a low, mean crestal bone loss at 36
      month follow-up was recorded but implant positioning in the apico-occlusal
      dimension was found to be the most significant variable that influenced bone
      loss. (J Oral Sci 58, 49-57, 2016). 

PMID- 27021541
TI  - Comparison of MMP2 and MMP9 expression levels between primary and metastatic
      regions of oral squamous cell carcinoma.
AB  - Matrix metalloproteinases (MMPs) and tumor-associated macrophages (TAMs) play
      important roles in tumor growth. The present study investigated the expression
      levels of MMP2 and MMP9 in relation to the distribution of TAMs in the primary
      and metastatic regions of oral squamous cell carcinoma. Twenty-nine cases of oral
      squamous cell carcinoma (OSCC) with regional lymph node metastasis were selected
      from available documents in the archives of the Department of Pathology, Nihon
      University School of Dentistry. Four-micrometer-thick sections were prepared from
      the primary and metastatic regions. Each section was subjected to
      immunohistochemical staining using anti-MMP2, anti-MMP9, and anti-CD68
      antibodies. The distribution and localization of MMPs and TAMs were compared
      between primary and metastatic regions. The expression levels of both MMPs were
      higher in the metastatic regions of lingual and gingival cancers. Statistically
      significant differences were observed in both T1 and T2 cases. In contrast to the
      higher expression of MMPs in metastatic regions, a higher number of TAMs were
      distributed in the primary regions. From these results, MMP expression levels and
      the numbers of TAMs were expected to have an inverse relationship between the
      primary and metastatic regions of OSCC. (J Oral Sci 58, 59-65, 2016). 

PMID- 27021542
TI  - Incidence and survival rates for malignant salivary gland tumors.
AB  - The aims of this study were to determine the incidence of malignant salivary
      gland tumors (MSGTs) in a specific in Spanish Mediterranean population, evaluate
      oncological outcomes, and identify prognostic factors for survival. Overall
      survival and disease-free survival rates were calculated for 23 patients with
      MSGTs who were treated in our department during 2004-2012. In the recruitment
      population of the reference hospital, annual incidence per 100,000 inhabitants
      was estimated, with corresponding 95% confidence intervals (CIs). The mean annual
      incidence of MSGTs was 0.91 new cases per 100,000 inhabitants (95% CI, 0.14
      2.83). The most common histological type was squamous cell carcinoma (34.8%).
      Overall survival ranged from 2 to 120 months (mean 70.5 months). The 5-year
      overall survival rate was 52.5%, and the 5-year disease-free survival rate was
      50%. The mean disease-free interval was 73.9 months (95% CI 47.1-100.7).
      Metastatic spread, tumor stage, perineural invasion, a submaxillary location,
      tumor size, histological grade, positive lymph node status, and presence of
      positive surgical resection margins were the most important factors in patient
      survival. Our results are consistent with those of other studies in relation to
      disease incidence but differ somewhat with respect to histological type. (J Oral
      Sci 58, 67-73, 2016). 

PMID- 27021543
TI  - Association between dental anomalies and malocclusion in Brazilian orthodontic
      patients.
AB  - Developmental dental anomalies have been associated with different malocclusions
      in various populations. This study verified this association in Brazilian non
      syndromic orthodontic patients. The prevalence of dental anomalies was evaluated
      by examining 2,052 pretreatment records of orthodontic patients. Panoramic
      radiographs, study designs, intraoral photographs and medical history were
      collected in order to identify hypodontia, hyperdontia, microdontia, macrodontia,
      taurodontism, transposition, impaction, and ectopia. Epidemiological data and
      classification of malocclusion were also obtained. Data were analyzed using chi
      square and Fisher's exact test (P < 0.05), and the prevalence ratio was obtained
      from cases that had a significant association between anomaly and malocclusion.
      The results showed that 27.4% of the patients evaluated had some dental anomaly,
      and most of them were white women aged 11-20 years. Ectopia, microdontia,
      impaction, and hypodontia were more prevalent in patients with Class I
      malocclusion. Macrodontia was the only anomaly associated with Class II division
      1. Impaction was associated with Class III malocclusion, at a 1.84-times higher
      prevalence. In conclusion, impaction was correlated with Class I malocclusion;
      macrodontia showed association with Class II division 1; and impaction and
      ectopia were associated with Class III malocclusion in Brazilian orthodontic
      patients. (J Oral Sci 58, 75-81, 2016). 

PMID- 27021544
TI  - Assessment of oral malodor and tonsillar microbiota after gargling with
      benzethonium chloride.
AB  - The oropharyngeal area can be a source of halitosis. However, the relationship
      between healthy tonsillar microbiota and halitosis is poorly understood. We
      conducted a pilot clinical study to clarify the effect of gargling with an
      antiseptic agent on tonsillar microbiota in patients with halitosis. Twenty-nine
      halitosis patients who did not have otolaryngologic disease or periodontitis were
      assigned randomly to one of three groups: benzethonium chloride (BZC) gargle;
      placebo gargle; no gargle. Concentrations of volatile sulfur compounds (VSCs) in
      mouth air, the organoleptic score (ORS) and tongue-coating score (TCS) were
      measured before and after testing. Tonsillar microbiota were assessed by
      detection of periodontal pathogens, and profiling with terminal-restriction
      fragment length polymorphism (T-RFLP) analysis and sequencing of 16SrRNA clone
      libraries for taxonomic assignment. Gargling with BZC reduced the concentrations
      of methyl mercaptan and hydrogen sulfide and the ORS, but did not affect the TCS
      or prevalence of periodontal pathogens. T-RFLP analyses and 16SrRNA clone
      sequencing showed a tendency for some candidate species to decrease in the test
      group. Although gargling of the oropharyngeal area with an antiseptic agent can
      reduce oral malodor, it appears that tonsillar microbiota are not influenced
      greatly. (J Oral Sci 58, 83-91, 2016). 

PMID- 27021545
TI  - Use of a laser displacement sensor with a non-contact electromagnetic vibration
      device for assessment of simulated periodontal tissue conditions.
AB  - A non-contact electromagnetic vibration device (NEVD) was previously developed to
      monitor the condition of periodontal tissues by assessing mechanical parameters.
      This system requires placement of an accelerometer on the target tooth, to detect
      vibration. Using experimental tooth models, we evaluated the performance of an
      NEVD system with a laser displacement sensor (LDS), which does not need an
      accelerometer. Simulated teeth (polyacetal rods) were submerged at various depths
      in simulated bone (polyurethane or polyurethane foam) containing simulated
      periodontal ligament (tissue conditioner). Then, mechanical parameters (resonant
      frequency, elastic modulus, and viscosity coefficient) were assessed using the
      NEVD with the following detection methods: Group 1, measurement with an
      accelerometer; Group 2, measurement with an LDS in the presence of the
      accelerometer; and Group 3, measurement with an LDS in the absence of the
      accelerometer. Statistical analyses were performed using nonparametric methods (n
      = 5) (P < 0.05). The three mechanical parameters significantly increased with
      increasing depth. In addition, the mechanical parameters significantly differed
      between the polyurethane and polyurethane foam models. Although Groups 1 and 2
      did not significantly differ, most all mechanical parameters in Group 3 were
      significantly larger and more distinguishable than those in Groups 1 and 2. The
      LDS was more accurate in measuring mechanical parameters and better able to
      differentiate periodontal tissue conditions. (J Oral Sci 58, 93-99, 2016). 

PMID- 27021546
TI  - Effects of miR-223 on expression of IL-1beta and IL-6 in human gingival
      fibroblasts.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional
      expression by translational inhibition or mRNA degradation. miRNAs bind to target
      mRNAs through partial complementarity, and can regulate many genes. In the
      present study, we investigated the effects of miR-223 on the expression of
      inflammatory cytokines in human gingival fibroblasts (HGF). To determine the
      effects of miR-223 on the expressions of interleukin-1beta (IL-1beta) and IL-6,
      HGF were stimulated by IL-1beta (1 ng/mL) or tumor necrosis factor-alpha (TNF
      alpha; 10 ng/mL) and transfected with a miR-223 expression plasmid. Levels of
      mRNA for IL-1beta, IL-6, inhibitor of kappa-B kinase alpha (IKKalpha) and mitogen
      activated protein kinase phosphatase-5 (MKP-5) were measured by real-time PCR,
      and levels IL-1beta, IL-6 and IKKalpha protein were determined by enzyme-linked
      immunosorbent assay and Western blotting. Expression of IL-1beta and IL-6 mRNAs
      was induced by IL-1beta and TNF-alpha and further increased by miR-223
      overexpression. IL-1beta and TNF-alpha induced the expression of IL-1beta and IL
      6 mRNAs, and this was reduced by miR-223 inhibitor. Overexpression of miR-223
      decreased the levels of IKKalpha protein and MKP-5 mRNA in HGF. These findings
      indicate that miR-223 might control the inflammatory response via IKKalpha and
      MKP-5 in periodontal tissue. (J Oral Sci 58, 101-108, 2016). 

PMID- 27021547
TI  - A cone-beam computed tomography evaluation of facial asymmetry in unilateral
      cleft lip and palate individuals.
AB  - Our study aimed to examine facial asymmetry in patients with unilateral cleft lip
      and palates (UCLP) using cone-beam computed tomography (CBCT) and explore the
      factors responsible for lower facial asymmetry in these individuals. The
      experimental group included 21 adolescent patients with non-syndromic UCLP while
      the control group comprised 14 patients without any facial cleft defects. The
      maxillofacial regions of the patients in the two groups were scanned using CBCT,
      and the Mimics 10.01 software was used to analyze the images. Multiple linear
      stepwise regression analysis was used to explore the factors related to the
      deviation of the pogonion point (Pog). Comparison of the two groups showed that
      the position of the lateral point of the pyriform aperture and the length of the
      mandibular body exhibited significant asymmetry (P < 0.05). Pog in the UCLP group
      deviated to the cleft side (1.24 +/- 2.28 mm), and was related to B6L(R) to
      Sagittal plane, CdL(R) to Sagittal plane, and U6L(R) to LS plane. We concluded
      that significant differences between the cleft and non-cleft sides existed only
      around the cleft, and not in the deeper regions of the maxillary complex.
      Functional adaption may be the main reason responsible for chin deviation in UCLP
      individuals. (J Oral Sci 58, 109-115, 2016). 

PMID- 27021548
TI  - Wear characteristics of polished and glazed lithium disilicate ceramics opposed
      to three ceramic materials.
AB  - This study compared the wear characteristics of a heat-pressed lithium disilicate
      ceramic material opposed to feldspathic porcelain, a lithium disilicate glass
      ceramic, and zirconia materials. Ceramic plate specimens were prepared from
      feldspathic porcelain (EX-3 nA1B), lithium disilicate glass ceramics (e.max CAD
      MO1/C14), and zirconia (Katana KT 10) and then ground or polished. Rounded rod
      specimens were fabricated from heat-pressed lithium disilicate glass ceramic
      (e.max press LT A3) and then glazed or polished. A sliding wear testing apparatus
      was used for wear testing. Wear of glazed rods was greater than that of polished
      rods when they were abraded with ground zirconia, ground porcelain, polished
      porcelain, or polished lithium disilicate ceramics. For both glazed and polished
      rods, wear was greater when the rods were abraded with ground plates. The
      findings indicate that application of a polished surface rather than a glazed
      surface is recommended for single restorations made of heat-pressed lithium
      disilicate material. In addition, care must be taken when polishing opposing
      materials, especially those used in occlusal contact areas. (J Oral Sci 58, 117
      123, 2016). 

PMID- 27021549
TI  - Anti-inflammatory and cytotoxic effects of methanol, ethanol, and water extracts
      of Angelicae Dahuricae Radix.
AB  - Angelicae Dahuricae Radix has been used for the treatment of headaches, rhinitis,
      and colds in traditional medicine. Methanol, ethanol, and water extracts of
      Angelicae Dahuricae Radix were collected. A statistically significant reduction
      in the cellular viability of the mouse leukemic monocyte macrophage cell line was
      noted after treatment with water extracts of Angelicae Dahuricae Radix.
      Stimulation with lipopolysaccharides (LPS) for 24 h led to a robust increase in
      nitric oxide production, but Angelicae Dahuricae Radix at 400 MUg/mL
      concentration significantly suppressed nitric oxide produced by the LPS
      stimulated RAW 264.7 cells in 70% ethanol, absolute ethanol, 70% methanol,
      absolute methanol, and boiling water groups (P < 0.05). Pretreatment with
      absolute ethanol extract of Angelicae Dahuricae Radix suppressed the LPS
      stimulated inducible nitric oxide synthase, interleukin-1beta, and cycloxygenase
      2 expression. Angelicae Dahuricae Radix showed significant cytotoxic effects on
      the human adenocarcinoma cell line and keratin-forming cell line. (J Oral Sci 58,
      125-131, 2016). 

PMID- 27021550
TI  - Temporomandibular joint dislocation in a post-stroke patient with dysphagia
      caused by gastroesophageal reflux-related vomiting.
AB  - Temporomandibular joint dislocation (TMJ) is sometimes found in post-stroke
      patients, and most cases occurs involuntarily. This report describes a rare case
      of repeated, voluntary, TMJ in a 73-year-old woman with dysphagia and dysarthria.
      The cause of dislocation was suspected to be voluntary excessive mouth opening
      associated with gastroesophageal reflux-related vomiting and the desire to eject
      oral deposits resulting from hypoglossal and facial nerve paralyses. After an
      oral hygiene intervention, the frequency of TMJ dislocation decreased and finally
      disappeared. Thorough oral hygiene seemed to contribute to protection against TMJ
      dislocation. (J Oral Sci 58, 133-136, 2016). 

PMID- 27021551
TI  - Periodontal regeneration with 0.3% basic fibroblast growth factor (FGF-2) for a
      patient with aggressive periodontitis: a case report.
AB  - This case report describes the clinical efficacy of treatment with basic
      fibroblast growth factor (FGF-2) for periodontal regeneration. A patient with
      aggressive periodontitis participated in a clinical trial involving
      administration of 0.3% FGF-2 in comparison with a placebo control. To evaluate
      the efficacy of FGF-2, standardized radiographs were taken before surgery and at
      12, 24, and 36 weeks after FGF-2 treatment. The rate of increase in alveolar bone
      height was 86.9% at 36 weeks. The 6-year postoperative radiograph showed
      significant development of alveolar bone in comparison with the first visit. FGF
      2 treatment may be effective for periodontal regeneration in cases of aggressive
      periodontitis. (J Oral Sci 58, 137-140, 2016). 

PMID- 27021552
TI  - A huge osteolipoma involving the coronoid process: a case report.
AB  - A 28-year-old man visited our hospital with the chief complaint of trismus.
      Computed tomography revealed a well-defined, soft tissue tumor, 66 * 45 * 21 mm,
      with a distinct boundary in the inner region of the zygomatic arch. The mass
      contained various sizes of bone-like hard tissue, some of which adhered to the
      right coronoid process. A contrast-enhanced magnetic resonance image showed that
      the mass was composed mainly of adipose tissue. Tumorectomy was performed, and
      the histopathological diagnosis was osteolipoma. At 2-year follow-up, mouth
      opening had increased from 31 mm to 50 mm. (J Oral Sci 58, 141-144, 2016). 

PMID- 27021553
TI  - Low-grade cribriform cystadenocarcinoma arising from a minor salivary gland: a
      case report.
AB  - Low-grade cribriform cystadenocarcinoma (LGCCC) is a recently described rare
      tumor of the salivary gland; this tumor most frequently arises from the parotid
      gland. Here, we describe a case of LGCCC arising from a minor salivary gland in
      the buccal mucosa. A 72-year-old man had a small mass on the left buccal mucosa.
      The mass was completely resected, and the postoperative course was uneventful.
      Histopathologically, the tumor comprised a single cyst with intraductal
      proliferation. Based on these histopathological findings along with
      immunohistochemistry a diagnosis of LGCCC arising from a minor salivary gland was
      made. (J Oral Sci 58, 145-149, 2016). 

PMID- 27021554
TI  - Generation of the Fip1l1-Pdgfra fusion gene using CRISPR/Cas genome editing.

PMID- 27021557
TI  - Synthesis of polymeric nanoparticles containing reduced graphene oxide nanosheets
      stabilized by poly(ionic liquid) using miniemulsion polymerization.
AB  - Polymeric nanoparticles containing reduced graphene oxide (rGO) nanosheets have
      been prepared by aqueous miniemulsion radical polymerization of methyl
      methacrylate (MMA) utilizing poly(ionic liquid) (PIL) as stabilizer to
      effectively disperse the rGO nanosheets in the monomer phase. The PIL that gave
      the best results in terms of rGO dispersibility was a block copolymer of the
      ionic liquid monomer 1-(2-methacryloyloxyethyl)-3-butylimidazolium
      bis(trifluoromethanesulfonyl)amide ([Mbim][TFSA]) and MMA, the concept being that
      the MMA units impart solubility in the MMA monomer droplets whereas the IL units
      act as adsorption sites for rGO. The rGO dispersibility in vinyl monomer was
      demonstrated to be superior using the above PIL block copolymer compared to the
      corresponding statistical copolymer or PIL homopolymer. Overall, the approach
      developed demonstrates how PILs can be employed to conveniently switch (turn
      ON/OFF) the dispersibility of PIL/rGO via anion exchange reactions, which can be
      an efficient strategy for synthesis of polymer/rGO nanocomposite materials.

PMID- 27021556
TI  - Anti-Anginal and Metabolic Effects of Carvedilol and Atenolol in Patients with
      Stable Angina Pectoris: A Prospective, Randomized, Parallel, Open-Label Study.
AB  - BACKGROUND: While recent guidelines have suggested the potential for beta
      blockers as first-line agents in chronic stable angina, few data regarding
      comparative anti-anginal and metabolic effects between beta-blockers with and
      without vasodilating properties have been reported, particularly in patients with
      angina pectoris. OBJECTIVE: Our objective was to compare the anti-anginal and
      metabolic effects of carvedilol and atenolol in patients with stable angina
      pectoris. METHODS: A total of 89 patients (mean age 54.9 +/- 9.3 years; male 53.9
      %) with stable angina pectoris were randomly assigned to carvedilol (n = 43) or
      atenolol (n = 46). The subjects undertook an exercise treadmill test and
      completed the Seattle Angina Questionnaire (SAQ); metabolic parameters were
      measured at baseline and 6 months after treatment. RESULTS: The baseline
      characteristics of both groups were well balanced. Both carvedilol and atenolol
      significantly reduced heart rate from baseline (76 +/- 11 to 66 +/- 9 beat/min, p
      < 0.001; 74 +/- 9 to 64 +/- 9 beat/min, p < 0.001, respectively) with no
      significant changes in systolic and diastolic blood pressure. Improvement of time
      to ST-segment depression during the treadmill exercise and the SAQ scores for
      angina stability and frequency after 6 months of treatment were similar between
      groups. There was no significant change from baseline in the level of fasting
      glucose, insulin, or glycated hemoglobin in either group. However, total
      cholesterol and low-density lipoprotein cholesterol levels significantly reduced
      to a greater extent with carvedilol than with atenolol (-23 vs. -10 and -38 vs. 
      24 %, respectively, p < 0.05 for both), although the rate of statin use was
      comparable. No changes were seen in high-density lipoprotein cholesterol and
      triglyceride levels after 6 months of treatment in both groups compared with
      baseline. CONCLUSIONS: Both carvedilol and atenolol had a similar anti-anginal
      effect. Compared with atenolol, carvedilol might have more beneficial effects on
      lipid metabolism in patients with stable angina pectoris [ClinicalTrials.gov
      identifier: NCT02547597].

PMID- 27021555
TI  - COMT val158met polymorphism and molecular alterations in the human dorsolateral
      prefrontal cortex: Differences in controls and in schizophrenia.
AB  - The single nucleotide val158met polymorphism in catechol o-methyltransferase
      (COMT) influences prefrontal cortex function. Working memory, dependent on the
      dorsolateral prefrontal cortex (DLPFC), has been repeatedly shown to be
      influenced by this COMT polymorphism. The high activity COMT val isoform is
      associated with lower synaptic dopamine levels. Altered synaptic dopamine levels
      are expected to lead to molecular adaptations within the synapse and within DLPFC
      neural circuitry. In this human post mortem study using high quality DLPFC
      tissue, we first examined the influence of the COMT val158met polymorphism on
      markers of dopamine neurotransmission, N-methyl-d-aspartate (NMDA) receptor
      subunits and glutamatic acid decarboxylase 67 (GAD67), all known to be critical
      to DLPFC circuitry and function. Next, we compared target gene expression
      profiles in a cohort of control and schizophrenia cases, each characterized by
      COMT genotype. We find that the COMT val allele in control subjects is associated
      with significant upregulation of GluN2A and GAD67 mRNA levels compared to met
      carriers. Comparisons between control and schizophrenia groups reveal that
      GluN2A, GAD67 and DRD2 are differentially regulated between diagnostic groups in
      a genotype specific manner. Chronic antipsychotic treatment in rodents did not
      explain these differences. These data demonstrate an association between
      COMTval158met genotype and gene expression profile in the DLPFC of controls,
      possibly adaptations to maintain DLPFC function. In schizophrenia val
      homozygotes, these adaptations are not seen and could reflect pathophysiologic
      mechanisms related to the known poorer performance of these subjects on DLPFC
      dependent tasks. 

PMID- 27021558
TI  - Mouse model of chromosome mosaicism reveals lineage-specific depletion of
      aneuploid cells and normal developmental potential.
AB  - Most human pre-implantation embryos are mosaics of euploid and aneuploid cells.
      To determine the fate of aneuploid cells and the developmental potential of
      mosaic embryos, here we generate a mouse model of chromosome mosaicism. By
      treating embryos with a spindle assembly checkpoint inhibitor during the four- to
      eight-cell division, we efficiently generate aneuploid cells, resulting in embryo
      death during peri-implantation development. Live-embryo imaging and single-cell
      tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that
      the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal
      lineage are eliminated by apoptosis, whereas those in the placental lineage show
      severe proliferative defects. Overall, the proportion of aneuploid cells is
      progressively depleted from the blastocyst stage onwards. Finally, we show that
      mosaic embryos have full developmental potential, provided they contain
      sufficient euploid cells, a finding of significance for the assessment of embryo
      vitality in the clinic. 

PMID- 27021559
TI  - Single-Cell Analysis of the Dps Response to Oxidative Stress.
AB  - Microorganisms have developed an elaborate spectrum of mechanisms to respond and
      adapt to environmental stress conditions. Among these is the expression of dps,
      coding for the DNA-binding protein from starved cells. Dps becomes the dominant
      nucleoid-organizing protein in stationary-phase Escherichia coli cells and is
      required for robust survival under stress conditions, including carbon or
      nitrogen starvation, oxidative stress, metal exposure, and irradiation. To study
      the complex regulation of Dps in E. coli, we utilized time-lapse fluorescence
      microscopy imaging to examine the kinetics, input encoding, and variability of
      the Dps response in single cells. In the presence of an oxidative stressor, we
      observed a single pulse of activation of Dps production. Increased concentrations
      of H2O2 led to increased intensity and duration of the pulse. While lower
      concentrations of H2O2 robustly activated the Dps response with little effect on
      the growth rate, higher concentrations of H2O2 resulted in dramatically lower and
      highly varied growth rates. A comparison of cells exposed to the same
      concentration of H2O2 revealed that increased levels of Dps expression did not
      confer a growth advantage, indicating that recovery from stress may rely
      primarily upon variation in the amount of damage caused to individual cells.
      IMPORTANCE: We show for the first time the response of the DNA-binding protein
      from starved cells (Dps) to oxidative stress in single cells of E. coli Through
      time-lapse fluorescence microscopy, a single pulse of Dps production is observed
      in cells exposed to H2O2, with a duration and intensity of induction proportional
      to the concentration of the applied stress. More intense Dps expression did not
      provide a growth benefit to the bacteria, suggesting that healing from oxidative
      stress may largely depend upon the amount of damage in each individual cell.

PMID- 27021560
TI  - Structure and Mutational Analyses of Escherichia coli ZapD Reveal Charged
      Residues Involved in FtsZ Filament Bundling.
AB  - Bacterial cell division is an essential and highly coordinated process. It
      requires the polymerization of the tubulin homologue FtsZ to form a dynamic ring
      (Z-ring) at midcell. Z-ring formation relies on a group of FtsZ-associated
      proteins (Zap) for stability throughout the process of division. In Escherichia
      coli, there are currently five Zap proteins (ZapA through ZapE), of which four
      (ZapA, ZapB, ZapC, and ZapD) are small soluble proteins that act to bind and
      bundle FtsZ filaments. In particular, ZapD forms a functional dimer and interacts
      with the C-terminal tail of FtsZ, but little is known about its structure and
      mechanism of action. Here, we present the crystal structure of Escherichia coli
      ZapD and show it forms a symmetrical dimer with centrally located alpha-helices
      flanked by beta-sheet domains. Based on the structure of ZapD and its chemical
      cross-linking to FtsZ, we targeted nine charged ZapD residues for modification by
      site-directed mutagenesis. Using in vitro FtsZ sedimentation assays, we show that
      residues R56, R221, and R225 are important for bundling FtsZ filaments, while
      transmission electron microscopy revealed that altering these residues results in
      different FtsZ bundle morphology compared to those of filaments bundled with wild
      type ZapD. ZapD residue R116 also showed altered FtsZ bundle morphology but
      levels of FtsZ bundling similar to that of wild-type ZapD. Together, these
      results reveal that ZapD residues R116, R221, and R225 likely participate in
      forming a positively charged binding pocket that is critical for bundling FtsZ
      filaments. IMPORTANCE: Z-ring assembly underpins the formation of the essential
      cell division complex known as the divisome and is required for recruitment of
      downstream cell division proteins. ZapD is one of several proteins in E. coli
      that associates with the Z-ring to promote FtsZ bundling and aids in the overall
      fitness of the division process. In the present study, we describe the dimeric
      structure of E. coli ZapD and identify residues that are critical for FtsZ
      bundling. Together, these results advance our understanding about the formation
      and dynamics of the Z-ring prior to bacterial cell division.

PMID- 27021561
TI  - Regulation by ToxR-Like Proteins Converges on vttRB Expression To Control Type 3
      Secretion System-Dependent Caco2-BBE Cytotoxicity in Vibrio cholerae.
AB  - Genes carried on the type 3 secretion system (T3SS) pathogenicity island of
      Vibrio cholerae non-O1/non-O139 serogroup strain AM-19226 must be precisely
      regulated in order for bacteria to cause disease. Previously reported results
      showed that both T3SS function and the presence of bile are required to cause
      Caco2-BBE cell cytotoxicity during coculture with strain AM-19226. We therefore
      investigated additional parameters affecting in vitro cell death, including
      bacterial load and the role of three transmembrane transcriptional regulatory
      proteins, VttRA, VttRB, and ToxR. VttRA and VttRB are encoded on the horizontally
      acquired T3SS genomic island, whereas ToxR is encoded on the ancestral
      chromosome. While strains carrying deletions in any one of the three
      transcriptional regulatory genes are unable to cause eukaryotic cell death, the
      results of complementation studies point to a hierarchy of regulatory control
      that converges on vttRB expression. The data suggest both that ToxR and VttRA act
      upstream of VttRB and that modifying the level of either vttRA or vttRB
      expression can strongly influence T3SS gene expression. We therefore propose a
      model whereby T3SS activity and, hence, in vitro cytotoxicity are ultimately
      regulated by vttRB expression. IMPORTANCE: In contrast to O1 and O139 serogroup
      V. cholerae strains that cause cholera using two main virulence factors (toxin
      coregulated pilus [TCP] and cholera toxin [CT]), O39 serogroup strain AM-19226
      uses a type 3 secretion system as its principal virulence mechanism. Although the
      regulatory network governing TCP and CT expression is well understood, the
      factors influencing T3SS-associated virulence are not. Using an in vitro
      mammalian cell model to investigate the role of three ToxR-like transmembrane
      transcriptional activators in causing T3SS-dependent cytotoxicity, we found that
      expression levels and a hierarchical organization were important for promoting
      T3SS gene expression. Furthermore, our results suggest that horizontally
      acquired, ToxR-like proteins act in concert with the ancestral ToxR protein to
      orchestrate T3SS-mediated pathogenicity.

PMID- 27021562
TI  - Enterococcal Sex Pheromones: Evolutionary Pathways to Complex, Two-Signal
      Systems.
AB  - Gram-positive bacteria carry out intercellular communication using secreted
      peptides. Important examples of this type of communication are the enterococcal
      sex pheromone systems, in which the transfer of conjugative plasmids is
      controlled by intercellular signaling among populations of donors and recipients.
      This review focuses on the pheromone response system of the conjugative plasmid
      pCF10. The peptide pheromones regulating pCF10 transfer act by modulating the
      ability of the PrgX transcription factor to repress the transcription of an
      operon encoding conjugation functions. Many Gram-positive bacteria regulate
      important processes, including the production of virulence factors, biofilm
      formation, sporulation, and genetic exchange using peptide-mediated signaling
      systems. The key master regulators of these systems comprise the RRNPP
      (RggRap/NprR/PlcR/PrgX) family of intracellular peptide receptors; these
      regulators show conserved structures. While many RRNPP systems include a core
      module of two linked genes encoding the regulatory protein and its cognate
      signaling peptide, the enterococcal sex pheromone plasmids have evolved to a
      complex system that also recognizes a second host-encoded signaling peptide.
      Additional regulatory genes not found in most RRNPP systems also modulate signal
      production and signal import in the enterococcal pheromone plasmids. This review
      summarizes several structural studies that cumulatively demonstrate that the
      ability of three pCF10 regulatory proteins to recognize the same 7-amino-acid
      pheromone peptide arose by convergent evolution of unrelated proteins from
      different families. We also focus on the selective pressures and
      structure/function constraints that have driven the evolution of pCF10 from a
      simple, single-peptide system resembling current RRNPPs in other bacteria to the
      current complex inducible plasmid transfer system.

PMID- 27021563
TI  - Evolution of Ecological Diversity in Biofilms of Pseudomonas aeruginosa by
      Altered Cyclic Diguanylate Signaling.
AB  - The ecological and evolutionary forces that promote and maintain diversity in
      biofilms are not well understood. To quantify these forces, three Pseudomonas
      aeruginosa populations were experimentally evolved from strain PA14 in a daily
      cycle of attachment, assembly, and dispersal for 600 generations. Each biofilm
      population evolved diverse colony morphologies and mutator genotypes defective in
      DNA mismatch repair. This diversity enhanced population fitness and biofilm
      output, owing partly to rare, early colonizing mutants that enhanced attachment
      of others. Evolved mutants exhibited various levels of the intracellular signal
      cyclic-di-GMP, which associated with their timing of adherence. Manipulating
      cyclic-di-GMP levels within individual mutants revealed a network of interactions
      in the population that depended on various attachment strategies related to this
      signal. Diversification in biofilms may therefore arise and be reinforced by
      initial colonists that enable community assembly. IMPORTANCE: How biofilm
      diversity assembles, evolves, and contributes to community function is largely
      unknown. This presents a major challenge for understanding evolution during
      chronic infections and during the growth of all surface-associated microbes. We
      used experimental evolution to probe these dynamics and found that diversity,
      partly related to altered cyclic-di-GMP levels, arose and persisted due to the
      emergence of ecological interdependencies related to attachment patterns. Clonal
      isolates failed to capture population attributes, which points to the need to
      account for diversity in infections. More broadly, this study offers an
      experimental framework for linking phenotypic variation to distinct ecological
      strategies in biofilms and for studying eco-evolutionary interactions.

PMID- 27021564
TI  - Assessment of carotid plaque neovascularization by contrast-enhanced ultrasound
      and high sensitivity C-reactive protein test in patients with acute cerebral
      infarction: a comparative study.
AB  - Vulnerable carotid plaque easily ruptures and causes cerebral infarction. Plaque
      inflammation and neovascularization have both been shown as important
      characteristics in vulnerable plaque. We assessed neovascularization within
      carotid plaque using contrast-enhanced ultrasound, and also assessed
      inflammation, using high sensitivity C-reactive protein (hs-CRP) testing, in
      acute cerebral infarction patients. A total of 106 patients with acute cerebral
      infarction and 40 controls were enrolled in the study. All subjects had been
      previously found to have carotid atherosclerotic plaques, and the plaques were
      classified as soft plaque, hard plaque, mixed plaque, and calcified plaque, using
      carotid artery ultrasound. Contrast-enhanced ultrasound was performed on the
      plaques for quantitative analysis and hs-CRP levels were measured. The results
      showed that plaque enhancement was present in 81.1 % of cerebral infarction
      patients and 40.0 % of controls. The contrast parameters for cerebral infarction
      patients were significantly different from controls. For cerebral infarction
      patients, soft plaque showed the highest enhanced percentage, 95.1 %, with
      contrast parameters significantly different to other types of plaque. The hs-CRP
      levels of enhanced cerebral infarction patients were higher than in non-enhanced
      patients. Correlation analysis in cerebral infarction patients showed that hs-CRP
      levels were closely related to the contrast parameters. Acute cerebral infarction
      patients showed intense contrast enhancement and inflammation in carotid plaque,
      and different types of plaque had various degrees of enhancement, suggesting that
      contrast-enhanced ultrasound and hs-CRP might be used for plaque risk
      stratification. 

PMID- 27021565
TI  - Ataxia with vitamin E deficiency caused by a new compound heterozygous mutation.

PMID- 27021567
TI  - Pharmacogenetic Risk Scores for Perindopril Clinical and Cost Effectiveness in
      Stable Coronary Artery Disease: When Are We Ready to Implement?

PMID- 27021566
TI  - Individualized Angiotensin-Converting Enzyme (ACE)-Inhibitor Therapy in Stable
      Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The
      PERindopril GENEtic (PERGENE) Risk Model.
AB  - BACKGROUND: Patients with stable coronary artery disease (CAD) constitute a
      heterogeneous group in which the treatment benefits by angiotensin-converting
      enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to
      integrate clinical and pharmacogenetic determinants in an ultimate combined risk
      prediction model. METHODS AND RESULTS: Clinical, genetic, and outcomes data were
      used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of
      perindopril versus placebo. Multivariable analysis of phenotype data resulted in
      a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms
      (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in
      the bradykinin type I-receptor gene) were used to construct a pharmacogenetic
      risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients
      (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal
      myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow
      up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients
      with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to
      treat ranged from as low as 29 (clinical risk score >=10 and PGXscore of 0) to
      521 (clinical risk score <=6 and PGXscore of 2). Furthermore, our data suggest
      that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is
      cost-effective. CONCLUSIONS: Both baseline clinical phenotype, as well as
      genotype determine the efficacy of widely prescribed ACE inhibition in stable
      CAD. Integration of clinical and pharmacogenetic determinants in a combined risk
      prediction model demonstrated a very wide range of gradients of absolute
      treatment benefit.

PMID- 27021568
TI  - Challenges During a Chlorine Gas Emergency Response.
AB  - OBJECTIVE: A chlorine gas release occurred at a poultry processing plant as a
      result of an accidental mixing of sodium hypochlorite and an acidic antimicrobial
      treatment. We evaluated the public health and emergency medical services response
      and developed and disseminated public health recommendations to limit the impact
      of future incidents. METHODS: We conducted key informant interviews with the
      state health department; local fire, emergency medical services, and police
      departments; county emergency management; and representatives from area hospitals
      to understand the response mechanisms employed for this incident. RESULTS: After
      being exposed to an estimated 40-pound chlorine gas release, 170 workers were
      triaged on the scene and sent to 5 area hospitals. Each hospital redistributed
      staff or called in extra staff (eg, physicians, nurses, and respiratory
      therapists) in response to the event. Interviews with hospital staff emphasized
      the need for improved communication with responders at the scene of a chemical
      incident. CONCLUSIONS: While responding, hospitals handled the patient surge
      without outside assistance because of effective planning, training, and drilling.
      The investigation highlighted that greater interagency communication can play an
      important role in ensuring that chemical incident patients are managed and
      treated in a timely manner. (Disaster Med Public Health Preparedness. 2016;10:553
      556).

PMID- 27021569
TI  - Quality control in oocytes by p63 is based on a spring-loaded activation
      mechanism on the molecular and cellular level.
AB  - Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for
      long periods of time, during which the high concentration of the p53 family
      member TAp63alpha sensitizes them to DNA damage-induced apoptosis. TAp63alpha is
      kept in an inactive and exclusively dimeric state but undergoes rapid
      phosphorylation-induced tetramerization and concomitant activation upon detection
      of DNA damage. Here we show that the TAp63alpha dimer is a kinetically trapped
      state. Activation follows a spring-loaded mechanism not requiring further
      translation of other cellular factors in oocytes and is associated with unfolding
      of the inhibitory structure that blocks the tetramerization interface. Using a
      combination of biophysical methods as well as cell and ovary culture experiments
      we explain how TAp63alpha is kept inactive in the absence of DNA damage but
      causes rapid oocyte elimination in response to a few DNA double strand breaks
      thereby acting as the key quality control factor in maternal reproduction.

PMID- 27021570
TI  - Real-time PCR for sexing Schistosoma mansoni cercariae.
AB  - The gender of cercarial larvae can only be determined using molecular methods.
      End point PCR methods that amplify repetitive markers on the W chromosome of the
      female (ZW) parasites have been developed, but sometimes results are ambiguous or
      incorrect. To more effectively distinguish sexes, and to determine why end point
      PCR can be incorrect, we quantified the W6 repeat sequence and a specific Z
      chromosome gene using real-time PCR. The ratio between copy number of W6 and a Z
      chromosome marker unambiguously identifies gender: females have higher ratios
      (421-4371) than males (0-21). However, some males have low numbers of W6 elements
      in their genome, and qPCR demonstrated significantly higher W6/Z marker ratios
      for male genotypes giving ambiguous end point PCR results compared with males
      giving clear end point results. The quantitative PCR sexing method developed will
      be particularly useful where reliable sexing of cercariae is critical, for
      example when staging genetic crosses. 

PMID- 27021571
TI  - Maxi-circles, glycosomes, gene transposition, expression sites, transsplicing,
      transferrin receptors and base J.
AB  - This is a personal story of the author of his research on trypanosomatids,
      covering a period of 1970-2015. Some of the highlights include the discovery of
      new aspects of kDNA, the mini-circle heterogeneity and the maxi-circle; the
      glycosome; the discovery of gene transposition as a major mechanism for antigenic
      variation; trans-splicing as an essential step in the synthesis of all
      trypanosome mRNAs; Pulsed Field Gradient gels to size-fractionate chromosome
      sized DNA molecules of protozoa; the sequence of trypanosome telomeres and their
      growth and contraction; the first ABC-transporter of trypanosomatids, LtpgpA; the
      variable transferrin receptor of T. brucei and its role in Fe uptake; and base J,
      its structure, biosynthesis and function. 

PMID- 27021572
TI  - Baxter's syndrome.

PMID- 27021573
TI  - Asthma control and cold weather-related respiratory symptoms.
AB  - BACKGROUND: In the northern hemisphere people are exposed recurrently to cold air
      and asthmatics experience more respiratory symptoms. We hypothesized that
      subjects with poor asthma control are more prone to experience cold weather
      related respiratory symptoms than those with good asthma control. METHODS: A
      population-based cross-sectional study of 1995 adult asthmatics (response rate
      40.4%) living in the Northern Finland was conducted using a questionnaire where
      cold weather-related respiratory symptoms as well as questions related to asthma
      control were inquired. The Asthma Control Test (ACT) was defined based on five
      questions (disadvantage and occurrence of asthma symptoms, waking up because of
      asthma symptoms, use of rescue medication and self-assessment of asthma control
      during the past 4 weeks), and was divided into quartiles. RESULTS: Cold weather
      related respiratory symptoms were more frequent among asthmatics with poorly
      controlled asthma (ACT Q1 vs. ACT Q4); adjusted prevalence ratio (PR) for
      shortness of breath (men 1.47, 95% confidence interval 1.22-1.77; women 1.18,
      1.07-1.30), cough (men 1.10, 0.91-1.34; women 1.18, 1.08-1.30), wheezing (men
      1.91, 1.31-2.78; women 1.48, 1.17-1.87), phlegm production (men 1.51, 1.06-2.14;
      women 1.62, 1.27-2.08) and chest pain (men 4.47, 1.89-10.56; women 2.60, 1.64
      4.12). The relations between asthma control and symptom occurrence seemed
      stronger among smokers than never smokers and subjects with body mass index (BMI)
      below and above 25-30. CONCLUSIONS: Our study provides new evidence that subjects
      whose asthma is poorly controlled are more prone to experience cold weather
      related respiratory symptoms and even a slight worsening of asthma control
      increases symptom prevalences.

PMID- 27021574
TI  - Effects on pulmonary rehabilitation in patients with COPD or ILD: A retrospective
      analysis of clinical and functional predictors with particular emphasis on
      gender.
AB  - BACKGROUND: The response of patients in a pulmonary rehabilitation (PR) is
      essentially good. However, not all patients benefit from PR to the same extent.
      In this analysis we wanted to identify the impact of gender and other factors on
      PR outcomes in patients with chronic obstructive pulmonary disease (COPD) or
      interstitial lung disease (ILD). METHODS: Patients suffering from COPD (n = 1492)
      or ILD (n = 599), treated during an inpatient PR between 1997 and 2015, were
      analysed according to the effects of PR on exercise capacity and quality of life
      with regard to the impact of gender or other predictors by univariate and
      multivariate analyzes. RESULTS: In the group of COPD patients, 30% did not
      achieve the expected physical performance during the 6-min walk test (28% of
      female and 32% of male patients). However, the non-responders initially have had
      a higher 6-min walking distance (6-MWD) (p < 0.001) and both male and female
      showed a significant lower BODE index (p = 0.025) in the multivariate analysis.
      In the ILD-group, 37% females and 43% males were classified as non-responders
      with regard to the 6-MWD. Also in this group, the non-responders initially have
      had a higher 6-MWD (p < 0.001). All other variables (age, BMI, lung function,
      blood gases, C-reactive Protein, Haemoglobin or rehabilitation duration) had no
      influence on the outcome. CONCLUSION: Our study supports the positive effects of
      PR in COPD and ILD patients. In both groups, patients with the biggest
      limitations benefit most from PR. However, relevant gender differences or other
      predictors could not be found.

PMID- 27021575
TI  - Exhaled nitric oxide as a diagnostic tool for wheezing in preschool children: A
      diagnostic accuracy study.
AB  - BACKGROUND: Airways inflammation may precede pulmonary dysfunction in wheezing
      individuals. The fraction of exhaled nitric oxide (FENO) has been described as a
      useful method for wheezing diagnosis in children, however, its application
      requires evidence. This study aimed to determine the accuracy of FENO in
      identifying wheezing in preschoolers. METHODS: A cross-sectional study was
      carried out with children from 3 to 5 years old, from Brazilian day care centers
      and public schools. They were evaluated by FENO measurement through the single
      breath method, and by ATS-DLD-78-C questionnaire that is used as a gold standard
      to phenotype wheezing patterns. RESULTS: The sample consisted of 243 non-wheezing
      children, 118 non-recurrent wheezing and 62 recurrent wheezing. The means of FENO
      and confidence intervals of 95%, were 5.4 (CI 95%, 5.2-5.6); 7.5 (CI 95%, 6.9
      8.2) and 11.2 (CI 95%, 9.6-12.7), respectively. The sensitivity, specificity,
      positive and negative predictive FENO values in the 6 parts per billion (ppb) cut
      off point that best diagnosed wheezing of non-wheezing children, were: 65.5%,
      84.3%, 75.6% and 76.7%, respectively, with an area under the curve (AUC) = 0.77.
      At 10 ppb, the best cut-off points for differentiating recurrent wheezing of non
      recurrent wheezing were: 56.4%, 81.3%, 61.4%, 78.0%, respectively, with an AUC =
      0.69. The post-test probability for each FENO cut-off points was increased by 33%
      for wheezing and 20% for recurrent wheezing diagnosis when associated with
      clinical examination. CONCLUSION: FENO can provide a reliable and accurate method
      to discriminate the presence and type of wheezing in preschoolers with 92% of
      acceptable in this study population.

PMID- 27021576
TI  - Maternal and perinatal outcomes of pregnancies in women with cystic fibrosis--A
      single centre case-control study.
AB  - BACKGROUND: Due to increased survival, more women with cystic fibrosis become
      pregnant. However, studies on the specificities of pregnancy in CF versus healthy
      women are lacking. METHODS: In this retrospective case-control study, we compared
      the maternal and perinatal outcomes of 33 pregnancies in CF women who delivered
      in our maternity ward from December 2000 to December 2013 and were matched to 66
      controls. RESULTS: The median term of delivery was similar in cases and controls
      (38.1 +/- 1.6 vs 38.4 +/- 1.1 weeks gestation). Assisted reproductive technology
      pregnancies were more frequent in CF women (51% vs 3%, p < 0.001). In CF women,
      the initial BMI was lower (mean BMI 19.5 +/- 2.4 vs 22.4 +/- 4.9 kg/m(2); p =
      0.001) and pre-existing diabetes was more frequent (30% vs 3%; p < 0.001). Those
      differences persisted during pregnancy for weight gain (9.1 +/- 7.1 kg vs 13.3 +/
      6.4 kg; p = 0.001) and diabetes (48% vs 8%; p < 0.001). Spontaneous labor and
      vaginal deliveries were less frequent in CF than in controls (respectively 45% vs
      70%, p = 0.002; 51% vs 70%, p = 0.11). There was an equal number of caesarean
      sections (24% vs 21%; p = 0.80). Neonatal outcomes were similar in both groups,
      including birth weight (3042 +/- 91 g vs 3119 +/- 92 g). CONCLUSIONS:
      Multidisciplinary care of pregnancy in women with CF resulted in maternal and
      perinatal outcomes similar to those found in women in the general population.

PMID- 27021577
TI  - Whistle and cough pressures in children with neuromuscular disorders.
AB  - RATIONALE: Expiratory muscle strength is a determinant of cough function. Maximal
      static expiratory pressure (PEmax) manoeuvres are widely used but are limited by
      patient motivation and technique. The study hypothesized that whistle mouth (PmW)
      and cough gastric (PgasCough) pressures might provide additional tests of
      expiratory muscle strength in children and young adults with neuromuscular
      disease (NMD). METHODS: We retrospectively reviewed the data of lung function and
      respiratory muscle tests of all the patients with NMD followed in our centre
      between November 2001 and December 2013. PmW and PgasCough were compared to other
      common tests. RESULTS: Three hundred and four respiratory evaluations were
      performed in 143 patients, aged 3-29 years old. Seventy-two patients had 2 to 8
      evaluations. Median [interquartiles] PEmax (38 [28-54] cmH2O) did not differ
      significantly from PgasCough (45 [30-60] cmH2O) and both were significantly
      greater than PmW (30 [19-44] cmH2O). Significant good correlations were observed
      between all the expiratory muscle parameters. The best correlation was observed
      between PEmax and PmW (r = 0.812, p < 0.001). Moreover, good correlations were
      found between the percentage of predicted forced vital capacity and PmW (r =
      0.619, p < 0.001) and PgasCough (r = 0.568, p < 0.001). Concerning the whistle
      test, the non-invasive measurement highly correlated with invasive measurements.
      CONCLUSIONS: PmW and PgasCough are simple and valuable tests to assess expiratory
      muscle strength in children and young adults with NMD. These tests are
      particularly useful in children having difficulties to perform PEmax manoeuvre.
      They have the great advantage of their simplicity, but PgasCough is limited by
      its invasiveness.

PMID- 27021578
TI  - Is capnometry helpful in children with bronchiolitis?
AB  - BACKGROUND: Acute bronchiolitis is the most frequent lower respiratory tract
      infection in infants. Only small subsets of patients develop severe disease
      resulting in hospitalization despite having no identifiable risk factors. There
      is still a debate as to the role of capnometry in assessing ventilation in
      children with acute respiratory distress, and bronchiolitis in particular.
      METHODS: This was a prospective, single blind cohort study in which children
      younger than two years presenting to the emergency department (ED) with
      bronchiolitis were included. Our primary outcome was the correlation between the
      end tidal CO2 (EtCO2) and the clinical decision of hospital admission and
      discharge. Our secondary outcome measure was the correlation of EtCO2 upon
      arrival to the ED and clinical measures of bronchiolitis severity. Finally, by
      using multivariate models, we looked for other parameters that could contribute
      to the prediction of illness severity. RESULTS: One hundred and fourteen children
      with bronchiolitis were evaluated. Their median EtCO2 upon arrival to the ED was
      34 mmHg (range 24-65 mmHg). EtCO2 values upon admission or discharge were not
      statistically different among patients who were hospitalized and among those who
      were discharged from the ED. Among admitted patients, we found no correlation
      between capnometry readings at admission and number of oxygen desaturation days,
      nor with the length of hospitalization. Wang clinical respiratory severity score
      was found, by using multivariate models, to predict nasogastric tube need, oxygen
      desaturation days, and length of hospitalization. CONCLUSION: Capnometry readings
      upon arrival to the ED did not predict hospital admission or hospital discharge
      eligibility. Among hospitalized patients, EtCO2 did not correlate with the
      evaluated disease severity measures. Wang score was found to be the most
      consistent predictor of significant outcomes.

PMID- 27021579
TI  - The three tiers of screening for sarcoidosis organ involvement.
AB  - Sarcoidosis may involve any organ in the body. Organ involvement with sarcoidosis
      may go undetected. This manuscript addresses a suggested approach to screening
      for sarcoidosis organ involvement. As sarcoidosis organ involvement may never
      cause symptoms or clinical problems, it is not always necessary to expend the
      time or expense to detect all organs involved with sarcoidosis. On the other
      hand, some forms of sarcoidosis organ involvement may have potentially severe
      consequences such as permanent vision impairment from eye sarcoidosis and sudden
      death from cardiac sarcoidosis. We believe it useful to describe three tiers of
      screening for sarcoidosis organ involvement. The first tier of screening involves
      eliciting a medical history and performing a physical examination. This is a
      useful screen for all organs. The second tier of screening involves performing
      specific laboratory tests to search for specific sarcoidosis organ involvement,
      even if there is no clinical sign or symptom to suggest involvement of that
      organ. Such screening is only recommended for a limited number of specific
      organs. The third tier of screening is complex and involves the performance of
      multiple tests/algorithms or examinations by subspecialists to search for
      specific organ involvement. The third tier of screening is used to evaluate eye
      sarcoidosis, vitamin D dysregulation associated with sarcoidosis, and cardiac
      sarcoidosis. It is hoped that this approach to screening for sarcoidosis organ
      involvement will be a springboard for rigorous examination of this process that
      is likely to benefit sarcoidosis patients. 

PMID- 27021580
TI  - Klotho and smoking--An interplay influencing the skeletal muscle function
      deficits that occur in COPD.
AB  - BACKGROUND: Klotho is an 'anti-ageing' hormone and transmembrane protein; Klotho
      deficient mice develop a similar ageing phenotype to smokers including emphysema
      and muscle wasting. The objective of this study was to evaluate skeletal muscle
      and circulating Klotho protein in smokers and COPD patients and to relate Klotho
      levels to relevant skeletal muscle parameters. We sought to validate our findings
      by undertaking complimentary murine studies. METHODS: Fat free mass, quadriceps
      strength and spirometry were measured in 87 participants (61 COPD, 13 'healthy
      smokers' and 13 never smoking controls) in whom serum and quadriceps Klotho
      protein levels were also measured. Immunohistochemistry was performed to
      demonstrate the location of Klotho protein in human skeletal muscle and in mouse
      skeletal muscle in which regeneration was occurring following injury induced by
      electroporation. In a separate study, gastrocnemius Klotho protein was measured
      in mice exposed to 77 weeks of smoke or sham air. RESULTS: Quadriceps Klotho
      levels were lower in those currently smoking (p = 0.01), irrespective of
      spirometry, but were not lower in patients with COPD. A regression analysis
      identified current smoking status as the only independent variable associated
      with human quadriceps Klotho levels, an observation supported by the finding that
      smoke exposed mice had lower gastrocnemius Klotho levels than sham exposed mice
      (p = 0.005). Quadriceps Klotho levels related to local oxidative stress but were
      paradoxically higher in patients with established muscle wasting or weakness; the
      unexpected relationship with low fat free mass was the only independent
      association. Within locomotor muscle, Klotho localized to the plasma membrane and
      to centralized nuclei in humans and in mice with induced muscle damage. Serum
      Klotho had an independent association with quadriceps strength but did not relate
      to quadriceps Klotho levels or to spirometric parameters. CONCLUSIONS: Klotho is
      expressed in skeletal muscle and levels are reduced by smoking. Despite this,
      quadriceps Klotho protein expression in those with established disease appears
      complex as levels were paradoxically elevated in COPD patients with established
      muscle wasting. Whilst serum Klotho levels were not reduced in smokers or COPD
      patients and were not associated with quadriceps Klotho protein, they did relate
      to quadriceps strength.

PMID- 27021581
TI  - Zinc and immunity: An essential interrelation.
AB  - The significance of the essential trace element zinc for immune function has been
      known for several decades. Zinc deficiency affects immune cells, resulting in
      altered host defense, increased risk of inflammation, and even death. The
      micronutrient zinc is important for maintenance and development of immune cells
      of both the innate and adaptive immune system. A disrupted zinc homeostasis
      affects these cells, leading to impaired formation, activation, and maturation of
      lymphocytes, disturbed intercellular communication via cytokines, and weakened
      innate host defense via phagocytosis and oxidative burst. This review outlines
      the connection between zinc and immunity by giving a survey on the major roles of
      zinc in immune cell function, and their potential consequences in vivo.

PMID- 27021582
TI  - Acetylome study in mouse adipocytes identifies targets of SIRT1 deacetylation in
      chromatin organization and RNA processing.
AB  - SIRT1 is a key protein deacetylase that regulates cellular metabolism through
      lysine deacetylation on both histones and non-histone proteins. Lysine
      acetylation is a wide-spread post-translational modification found on many
      regulatory proteins and it plays an essential role in cell signaling,
      transcription and metabolism. In mice, SIRT1 has known protective functions
      during high-fat diet but the acetylome regulated by SIRT1 in adipocytes is not
      completely understood. Here we conducted acetylome analyses in murine adipocytes
      treated with small-molecule modulators that inhibit or activate the deacetylase
      activity of SIRT1. We identified a total of 302 acetylated peptides from 78
      proteins in this study. From the list of potential SIRT1 targets, we selected
      seven candidates and further verified that six of them can be deacetylated by
      SIRT1 in-vitro. Among them, half of the SIRT1 targets are involved in regulating
      chromatin structure and the other half is involved in RNA processing. Our results
      provide a resource for further SIRT1 target validation in fat cells and suggest a
      potential role of SIRT1 in the regulation of chromatin structure and RNA
      processing, which may possibly extend to other cell types as well.

PMID- 27021583
TI  - Effects of plasma irradiation using various feeding gases on growth of Raphanus
      sativus L.
AB  - In this work, we have studied the action of dielectric barrier discharge (DBD)
      plasma irradiation using various feeding gases on seeds of Raphanus sativus L.
      and analysis their growth. Our experimental data shows that Air, O2, and
      NO(10%)+N2 feeding gases plasma irradiation enhanced plant growth, whereas N2, He
      and Ar feeding gases plasma irradiation had little influence on plant growth.
      Moreover, humid air plasma irradiation was more effective in growth enhancement
      than dry one. More than 2.3 times faster growth was observed by 3 min air plasma
      irradiation with 40-90% relative humidity. The reactive species generated by
      plasma in gas phase were detected using optical emission spectroscopy and in
      liquid phase by electron spin resonance (ESR) spectroscopy. We concluded that OH
      and O radicals were key species for plant growth enhancement.

PMID- 27021584
TI  - Study of the diversity of microbial communities in a sequencing batch reactor
      oxic-settling-anaerobic process and its modified process.
AB  - To further reveal the mechanism of sludge reduction in the oxic-settling
      anaerobic (OSA) process, the polymerase chain reaction - denaturing gradient gel
      electrophoresis protocol was used to study the possible difference in the
      microbial communities between a sequencing batch reactor (SBR)-OSA process and
      its modified process, by analyzing the change in the diversity of the microbial
      communities in each reactor of both systems. The results indicated that the
      structure of the microbial communities in aerobic reactors of the 2 processes was
      very different, but the predominant microbial populations in anaerobic reactors
      were similar. The predominant microbial population in the aerobic reactor of the
      SBR-OSA belonged to Burkholderia cepacia, class Betaproteobacteria, while those
      of the modified process belonged to the classes Alphaproteobacteria,
      Betaproteobacteria, and Gammaproteobacteria. These 3 types of microbes had a
      cryptic growth characteristic, which was the main cause of a greater sludge
      reduction efficiency achieved by the modified process. 

PMID- 27021585
TI  - Correlation of Stomatitis and Cutaneous Toxicity With Clinical Outcome in
      Patients With Metastatic Renal-Cell Carcinoma Treated With Everolimus.
AB  - BACKGROUND: In clinical practice, discontinuation or dose reduction of everolimus
      may be induced not only by grade 3 or 4 toxicities but also by prolonged grade 2
      toxicities, such as stomatitis and/or cutaneous toxicity, which share some
      pathogenetic mechanisms. We assessed the correlation between either everolimus
      discontinuation or dose reduction induced by stomatitis-cutaneous toxicity events
      (SCTE) and clinical outcome of patients with metastatic renal-cell cancer (mRCC).
      PATIENTS AND METHODS: We retrospectively reviewed the clinical data of patients
      with mRCC treated with everolimus in 2 Italian centers. Clinical evidence of SCTE
      was evaluated, and corresponding clinical data were reviewed for response and
      clinical outcome. RESULTS: Seventy-nine mRCC patients treated with everolimus (57
      male, 22 female; median age 66 years; range, 44-88 years) were evaluated. SCTE
      were observed in 20 (25%) of 79 patients at a median of 30.5 days of everolimus
      treatment (range, 10-270 days). Partial response or stable disease was achieved
      in 15 (79%) of 19 evaluable patients with SCTE compared to 28 (48%) of 58 with no
      SCTE (P = .03). At a median follow-up of 19 months, a significant difference was
      found in the median PFS equal to 7.8 months (95% confidence interval [CI], 2.8
      24.4) in SCTE patients versus 4.3 months (95% CI, 2.7-7.5) in non-SCTE patients
      (P = .029), and in the median OS equal to 30.6 months (95% CI, 19.6-not reached)
      in SCTE patients versus 13.5 months (95% CI, 9.9-17.7) in non-SCTE patients (P =
      .0007). CONCLUSION: These data suggest that SCTE may be a predictive marker of
      favorable outcome in mRCC patients treated with everolimus.

PMID- 27021586
TI  - Anti-programmed Death Receptor 1 Blockade Induces Clinical Response in a Patient
      With Metastatic Collecting Duct Carcinoma.

PMID- 27021587
TI  - Prognostic Value of Gene Methylation and Clinical Factors in Non-Muscle-Invasive
      Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.
AB  - INTRODUCTION: To systematically analyze the outcomes and prognostic value of gene
      methylation and clinical parameters in non-muscle-invasive upper tract urothelial
      carcinoma (NMIUTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS:
      The methylation status of 10 selected genes and clinical parameters of 192
      NMIUTUC patients who received RNU and postoperative intravesical mitomycin were
      assessed. Univariate and multivariate Cox regression models were performed to
      evaluate the prognostic factors of cancer-specific mortality and intravesical
      recurrence. RESULTS: For 192 NMIUTUC patients, 1-, 3-, and 5-year cancer-specific
      survival (CSS)/bladder recurrence-free survival (BRFS) rates were 98.4%/86.4%,
      90.6%/74.6%, and 86.9%/62.4%, respectively. After the multivariate analysis, the
      methylation of ABCC6 (hazard ratio [HR], 3.46, P = .005), GDF15 (HR, 2.03, P =
      .002), multiple tumors (HR, 2.11, P = .049), impaired renal function (HR, 3.09, P
      = .004), and open RNU (HR, 2.14, P = .047) were independently associated with
      cancer-specific mortality, whereas the methylation of GDF15 (HR, 0.55, P = .022),
      RASSF1A (HR, 0.31, P = .006), multiple tumors (HR, 2.11, P = .002), and
      concomitant ipsilateral hydronephrosis (HR, 1.87, P = .022) were independently
      associated with intravesical recurrence after RNU. The c index of the
      multivariate model to predict cancer-specific mortality and intravesical
      recurrence was 0.81 and 0.78, respectively. CONCLUSION: As an early stage
      disease, NMIUTUC has better postoperative survival and later intravesical
      recurrence than upper tract urothelial carcinoma; however, the intravesical
      recurrence rate is not decreased. The nomogram can be used to accurately predict
      the oncologic outcomes of NMIUTUC patients and can be used to guide clinical
      decision making.

PMID- 27021588
TI  - Upper Tract Urothelial Carcinomas Accompanied by Previous or Synchronous
      Nonmuscle-Invasive Bladder Cancer and Preoperative Hydronephrosis Might Have
      Worse Oncologic Outcomes After Radical Nephroureterectomy.
AB  - BACKGROUND: The purpose of the study was to identify predictors of
      clinicopathologic features and oncologic outcomes in patients with upper tract
      urothelial carcinoma treated with radical nephroureterectomy (RNU). PATIENTS AND
      METHODS: The medical records of 172 patients treated with RNU from January 2001
      to September 2014 were retrospectively reviewed. Logistic regression and survival
      analysis methodology were respectively used to evaluate predictors of
      clinicopathologic features and oncologic outcomes. RESULTS: Of the enrolled 172
      patients, 80 (46.5%) had renal pelvic tumors, 67 (39%) had ureteral tumors, and
      the remaining 25 (14.5%) patients had multifocal tumors. Compared with patients
      with renal pelvic tumors, those with ureteral and multifocal tumors were more
      likely to have previous or synchronous nonmuscle-invasive bladder cancer (NMIBC)
      and severe hydronephrosis (P = .001 and P < .001, respectively). Logistic
      regression analysis showed that previous or synchronous NMIBC was significantly
      associated with worse renal function and high grade (P = .034 and P = .014,
      respectively), and severe hydronephrosis independently predicted worse renal
      function and positive lymph node or lymphovascular invasion status (P = .001 and
      P = .007, respectively). Moreover, severe hydronephrosis was an independent risk
      factor for overall survival and cancer-specific survival in multivariate analysis
      (P = .025 and P = .045, respectively). Multifocality and previous or synchronous
      NMIBC were significantly associated with bladder-recurrence-free survival (P =
      .023 and P = .001, respectively). CONCLUSION: Upper tract urothelial carcinoma
      accompanied by previous or synchronous NMIBC and preoperative severe
      hydronephrosis could have worse oncologic outcomes after RNU. These common
      accompanied diagnoses could be valuable for guiding preoperative planning and
      postoperative adjuvant therapy.

PMID- 27021589
TI  - Active control on high-order coherence and statistic characterization on random
      phase fluctuation of two classical point sources.
AB  - Young's double-slit or two-beam interference is of fundamental importance to
      understand various interference effects, in which the stationary phase difference
      between two beams plays the key role in the first-order coherence. Different from
      the case of first-order coherence, in the high-order optical coherence the
      statistic behavior of the optical phase will play the key role. In this article,
      by employing a fundamental interfering configuration with two classical point
      sources, we showed that the high- order optical coherence between two classical
      point sources can be actively designed by controlling the statistic behavior of
      the relative phase difference between two point sources. Synchronous position Nth
      order subwavelength interference with an effective wavelength of lambda/M was
      demonstrated, in which lambda is the wavelength of point sources and M is an
      integer not larger than N. Interestingly, we found that the synchronous position
      Nth-order interference fringe fingerprints the statistic trace of random phase
      fluctuation of two classical point sources, therefore, it provides an effective
      way to characterize the statistic properties of phase fluctuation for incoherent
      light sources. 

PMID- 27021590
TI  - Balancing current levels in children with bilateral cochlear implants using
      electrophysiological and behavioral measures.
AB  - Children have benefited from bilateral cochlear implants (CIs) over unilateral
      CIs despite often missing important periods in bilateral auditory development.
      This suggests a remarkable perceptual ability by children to "work around"
      abnormal changes in the auditory pathways. Nonetheless, these children rely
      primarily on interaural level differences as interaural timing cues are more
      difficult to access or detect. Mismatched levels provided to the two implants
      could distort interaural level cues thus compromising the benefits of bilateral
      CI use. We asked whether "balanced" or "centered" perception of bilateral input
      can be predicted by physiological or behavioral measures. Twenty-four children
      who had used unilateral CIs for 9.21 +/- 2.66 years prior to bilateral
      implantation participated. "Balanced bilateral levels" were identified by
      responses occurring with a probability of 50% on the right side of the head and
      50% on the left in a two choice lateralization task. Loudness judgments of
      current presented unilaterally by each implant were measured on a continuous
      visual scale. Maximum wave eV amplitudes were evoked unilaterally by each implant
      and matched amplitudes were identified. Balanced bilateral levels were predicted
      within 10 Clinical Units (CU) in 9 of 13 (69%) children using matched wave eV
      amplitudes. Bilaterally balanced levels were reasonably predicted by similar
      loudness judgments (<10% difference between CIs) in only 6 of 13 (46%) children.
      Results indicate that matching amplitudes of physiological responses can produce
      a balanced perception of bilateral input despite unilateral strengthening of the
      auditory pathways and can potentially be used clinically to provide a first
      approximation of balance/centered levels.

PMID- 27021591
TI  - Driving Task: How Older Drivers' On-Road Driving Performance Relates to
      Abilities, Perceptions, and Restrictions.
AB  - This study examined a cohort of 227 older drivers and investigated the
      relationship between performance on the electronic Driver Observation Schedule
      (eDOS) driving task and: (1) driver characteristics; (2) functional abilities;
      (3) perceptions of driving comfort and abilities; and (4) self-reported driving
      restrictions. Participants (male: 70%; age: M = 81.53 years, SD = 3.37 years)
      completed a series of functional ability measures and scales on perceived driving
      comfort, abilities, and driving restrictions from the Year 2 Candrive/Ozcandrive
      assessment protocol, along with an eDOS driving task. Observations of
      participants' driving behaviours during the driving task were recorded for
      intersection negotiation, lane-changing, merging, low-speed maneuvers, and
      maneuver-free driving. eDOS driving task scores were high (M = 94.74; SD = 5.70)
      and significantly related to participants' perceived driving abilities, reported
      frequency of driving in challenging situations, and number of driving
      restrictions. Future analyses will explore potential changes in driving task
      scores over time.

PMID- 27021592
TI  - High serum anti-BP180 IgE levels correlate to prominent urticarial lesions in
      patients with bullous pemphigoid.

PMID- 27021593
TI  - Opportunities for male involvement during pregnancy in Magu district, rural
      Tanzania.
AB  - BACKGROUND: Male involvement during antenatal care is promoted to be an important
      intervention to increase positive maternal and new born health outcomes. Despite
      active promotion to stimulate male involvement during antenatal care, few men in
      Tanzania accompany women to their antenatal care visits. This study aims to
      understand perceptions, attitudes and behaviour of men regarding their role and
      involvement during pregnancy and antenatal care visits in a rural district in
      Tanzania. METHODS: Data collection took place in Magu District between September
      2013 and March 2014, using a mixed method approach. This included observations at
      six government health facilities, nine focus group discussions (with a total of
      76 participants) and 26 semi-structured interviews of participants, included
      through convenience- and snowball sampling. Additionally, a questionnaire was
      distributed among 156 women attending antenatal care, regarding their partners'
      involvement in their pregnancy. Qualitative analysis was done through coding of
      themes based on the Three Delays Framework. Descriptive analysis was used for
      quantitative data. RESULTS: Male involvement in pregnancy and antenatal care in
      Magu district is low. Although men perceived antenatal care as important for
      pregnant women, most husbands had a passive attitude concerning their own
      involvement. Barriers for male involvement included: traditional gender roles,
      lack of knowledge, perceived low accessibility to join antenatal care visits and
      previous negative experiences in health facilities. CONCLUSION: Although several
      barriers impede male involvement during antenatal care, men's internal motivation
      and attitudes towards their role during pregnancy was generally positive.
      Increasing community awareness and knowledge about the importance of male
      involvement and increasing accessibility of antenatal clinics can reduce some of
      the barriers.

PMID- 27021594
TI  - HBxAg suppresses apoptosis of human placental trophoblastic cell lines via
      activation of the PI3K/Akt pathway.
AB  - The aim of this study is to investigate the effect of hepatitis B virus X (HBx)
      protein on the apoptosis of placental trophoblastic cells and its potential
      mechanism. A pcDNA3.1 expression vector of HBx gene was built and transfected
      into JEG-3 and HTR-8 human placental trophoblastic cell lines, respectively.
      After transfection for 48 h, RT-PCR and immunofluorescence analyses showed that
      HBx mRNA and protein expression was detected in JEG-3 and HTR-8 cells. Flow
      cytometry revealed that early apoptosis of JEG-3 and HTR-8 cells was reduced by
      pcDNA-HBx transfection. Immunofluorescence and Western blotting showed that PI3K
      and p-Akt were significantly upregulated in HTR-8 cells. HBx ectopic expression
      did not change the viability of JEG-3 and HTR-8 cells when the PI3K/Akt pathway
      was blocked by its specific inhibitor LY294002. Moreover, the pcDNA-PI3K
      expression vector and pcDNA-HBx were transfected individually or co-transfected
      into the cells. The results showed that pcDNA-PI3K/pcDNA-HBx co-transfection
      promoted the expression of PI3K protein compared with the pcDNA-PI3K transfection
      group but did not increase the expression of HBx protein compared with pcDNA-HBx
      transfection group. In conclusion, HBx gene can be transferred into JEG-3 and HTR
      8 human placental trophoblastic cell lines and cause inhibition of cell
      apoptosis. Its effect of apoptosis inhibition is related to the activation of the
      PI3K/Akt signaling pathway. 

PMID- 27021595
TI  - Reviving the critical distinction between perceived capability and motivation: a
      response to commentaries.

PMID- 27021596
TI  - The Role of Hope for Adolescents with a Chronic Illness: An Integrative Review.
AB  - Hope is a human strength essential for adolescents' enduring and coping with
      chronic illness however, the role of hope is not well understood in this
      population. OBJECTIVES: This integrative review describes what is currently known
      about the role of hope in adolescents with a chronic illness. METHOD: A
      methodological review using an integrative approach by R. Whittemore and K. Knafl
      (2005) was performed. DATABASES: MEDLINE via Pubmed; CINAHL; PyscINFO and Google
      scholar were searched for articles published in peer-reviewed journals from 1995
      to 2015, using search terms 'hope and chronic illness' with age limiters for all
      except Google scholar (title search of "hope and adolescents"). RESULTS: Of the
      197 studies initially retrieved: a total of 27 quantitative studies, 8
      qualitative studies and 19 theoretical works were selected for review. Seven
      themes emerged including that hope: (i) promotes health (ii) facilitates coping
      and adjustment, (iii) enhances quality of life, (iv) is essential in purpose in
      life and illness (v) improves self-esteem, (vi) is an important factor in
      resilience and (vii) affects maturation. Persons reporting higher levels of hope
      find multiple routes to goals, view setbacks as challenges, and better manage
      psychological symptoms. DISCUSSION: Although theory and a limited body of
      empirical research to date suggest a link between hopeful thinking and physical
      health, the specific mechanisms remain unclear. As hope is linked to resilience,
      further research should explore whether adolescents with higher hope return to
      baseline faster than their lower hope counterparts.

PMID- 27021597
TI  - Padma 28 for intermittent claudication.
AB  - BACKGROUND: Intermittent claudication (IC) is pain caused by chronic occlusive
      arterial disease that develops in a limb during exercise and is relieved with
      rest. Most drug treatments of IC have a limited effect in improving walking
      distance. Padma 28, a Tibetan herbal preparation, has been used to treat IC, but
      there is debate as to whether Padma 28 produces a clinical benefit beyond the
      placebo effect. This is an update of a review first published in 2013.
      OBJECTIVES: To determine whether Padma 28 is effective, compared with placebo or
      other medications, in increasing pain-free and maximum walking distance for
      patients with intermittent claudication. SEARCH METHODS: For this update the
      Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register
      (September 2015), the Cochrane Register of Studies ((CENTRAL) (2015, Issue 8))
      and clinical trials databases. SELECTION CRITERIA: Randomised controlled trials
      of Padma 28 compared with placebo or other pharmacological treatments in people
      suffering from IC. DATA COLLECTION AND ANALYSIS: All review authors independently
      assessed the selected studies and extracted the data. Risk of bias was evaluated
      independently by two review authors. Depending on the data provided in the
      individual trials, we extracted mean or median walking distance at the end of the
      trial, or change in walking distance over the course of the trial, or both. Where
      not provided, and whenever possible, the statistical significance of differences
      in these parameters between treatment and placebo groups in individual trials was
      calculated. Where possible, data were combined by meta-analysis. MAIN RESULTS: No
      new trials were identified in the search for this review update. In total five
      trials involving 365 participants were included in this review. All trials
      compared Padma 28 with placebo for at least 16 weeks of follow-up. Pain-free and
      maximum walking distances both increased significantly in the groups treated with
      Padma 28, with no significant change in the placebo group. In general, the
      studies presented results comparing the treatment arms before and after treatment
      but made no comparisons between the Padma 28 and placebo groups. Pooled data of
      maximum walking distance after treatment with Padma 28 and placebo from two
      studies (193 participants) indicated a higher maximum walking distance (mean
      difference (MD) 95.97 m, 95% confidence interval (CI) 79.07 m to 112.88 m, P <
      0.00001, very low quality evidence) in the Padma 28 group compared with placebo.
      The clinical importance of these observed changes in walking distance is unclear
      as no quality of life data were reported. There was no effect on ankle brachial
      index (ABI): change in ABI values between baseline and six months follow up MD 
      0.01, 95% CI -0.07 to 0.05, 1 study, 56 participants, P = 0.72, very low quality
      evidence). Mild side effects, especially gastrointestinal discomfort, tiredness
      and skin eruption, were reported but this outcome was not different between the
      Padma 28 and placebo groups (odds ratio 1.09, 95% CI 0.42 to 2.83, four studies,
      231 participants, P = 0.86, very low quality evidence). AUTHORS' CONCLUSIONS:
      Some evidence exists from individual trials to suggest that Padma 28 may be
      effective in increasing walking distances, at least in the short term (four
      months), in people with IC. Side effects do not appear to be a problem. However,
      the longer term effects of treatment are unknown and the clinical significance of
      the improvements in walking distance are questionable. Moreover, the quality of
      the evidence is limited by the small sample size of the available trials, limited
      reporting of statistical analyses that compared treatment groups, and relatively
      high withdrawal rates that were linked to the outcome. That is, patients were
      withdrawn if they failed to improve walking distance. There was also evidence of
      publication bias. We therefore feel there is currently insufficient evidence to
      draw conclusions regards the effectiveness of Padma 28 in the routine management
      of IC. Further well-designed research would be required to determine the true
      effects of this herbal preparation.

PMID- 27021598
TI  - Human periodontal ligament stem cells suppress T-cell proliferation via down
      regulation of non-classical major histocompatibility complex-like glycoprotein
      CD1b on dendritic cells.
AB  - BACKGROUND AND OBJECTIVE: Periodontal ligament stem cells (PDLSCs) from the
      periodontal ligament tissue were recently identified as mesenchymal stem cells
      (MSCs). The capabilities of PDLSCs in periodontal tissue or bone regeneration
      have been reported, but their immunomodulatory role in T-cell immune responses
      via dendritic cells (DCs), known as the most potent antigen-presenting cell, has
      not been studied. The aim of this study is to understand the immunological
      function of homogeneous human STRO-1+ CD146+ PDLSCs in DC-mediated T-cell immune
      responses to modulate the periodontal disease process. MATERIAL AND METHODS: We
      utilized highly purified (> 95%) human STRO-1+ CD146+ PDLSCs and human bone
      marrow mesenchymal stem cells (BMSCs). Each stem cell was co-cultured with human
      monocyte-derived DCs in the presence of lipopolysaccharide isolated from
      Porphyromonas gingivalis, a major pathogenic bacterium responsible for
      periodontal disease, in vitro to examine the immunological effect of each stem
      cell on DCs and DC-mediated T-cell proliferation. RESULTS: We discovered that
      STRO-1+ CD146+ PDLSCs, as well as BMSCs, significantly decreased the level of non
      classical major histocompatibility complex glycoprotein CD1b on DCs, resulting in
      defective T-cell proliferation, whereas most human leukocyte antigens and the co
      stimulatory molecules CD80 and CD86 in/on DCs were not significantly affected by
      the presence of BMSCs or STRO-1+ CD146+ PDLSCs. CONCLUSIONS: This study unveiled
      an immunomodulatory role of STRO-1+ CD146+ PDLSCs in negatively regulating DC
      mediated T-cell immune responses, demonstrating their potential to be utilized in
      promising new stem cell therapies.

PMID- 27021599
TI  - Morbidity and mortality in severely burned children with Clostridium difficile
      associated diarrhea.
AB  - BACKGROUND: Clostridium difficile is a key culprit underlying nosocomial
      infectious diarrhea. We investigated the effect of C difficile-associated
      diarrhea (CDAD) on morbidity and mortality in severely burned children and CDAD
      risk factors. METHODS: After review of 2,840 records, 288 pediatric burn patients
      were identified as having stool output of >10 mL*kg(-1)*min(-1) for >=2
      successive days and had stool samples immunoassayed for toxins A and B. A case
      control analysis was performed by matching cases to controls via logistic
      regression and propensity scores so that age, admission time, and time of
      occurrence could be controlled; the endpoints were mortality and hospitalization
      time. RESULTS: Eighteen patients tested positive for C difficile toxins (median
      age, 4 years; mean total body surface area burned, 59%). In the CDAD group,
      unadjusted in-hospital mortality was 28% (odds ratio, 5.4; 95% CI, 1.7-16.7; P =
      .01). Hospitalization averaged 48 days in the CDAD group and 38 days in the non
      CDAD group (P = .24). Duration of stay per percent total body surface area burned
      was greater in the CDAD group (0.82 +/- 0.4 vs 0.60 +/- 0.4; P = .03), as were
      prolonged bouts of diarrhea complicated by acidosis (13 +/- 16 vs 4 +/- 5 days; P
      < .005). Of the 18 possible risk factors evaluated, inhalation injury diagnosed
      at admission occurred more often in CDAD patients than matched controls (59% vs
      31%; P = .04). CONCLUSION: CDAD during hospitalization is associated with greater
      mortality after burns. Inhalation injury increases the likelihood of C difficile
      infection. Whether C difficile infection is an indication of greater illness
      among certain burned patients is unknown.

PMID- 27021600
TI  - Comments on: Clinical predictors of prolonged postresection hypotension after
      laparoscopic adrenalectomy for pheochromocytoma.

PMID- 27021601
TI  - Atmospheric fates of Criegee intermediates in the ozonolysis of isoprene.
AB  - We use a large laboratory, modeling, and field dataset to investigate the
      isoprene + O3 reaction, with the goal of better understanding the fates of the C1
      and C4 Criegee intermediates in the atmosphere. Although ozonolysis can produce
      several distinct Criegee intermediates, the C1 stabilized Criegee (CH2OO, 61 +/-
      9%) is the only one observed to react bimolecularly. We suggest that the C4
      Criegees have a low stabilization fraction and propose pathways for their
      decomposition. Both prompt and non-prompt reactions are important in the
      production of OH (28% +/- 5%) and formaldehyde (81% +/- 16%). The yields of
      unimolecular products (OH, formaldehyde, methacrolein (42 +/- 6%) and methyl
      vinyl ketone (18 +/- 6%)) are fairly insensitive to water, i.e., changes in
      yields in response to water vapor (<=4% absolute) are within the error of the
      analysis. We propose a comprehensive reaction mechanism that can be incorporated
      into atmospheric models, which reproduces laboratory data over a wide range of
      relative humidities. The mechanism proposes that CH2OO + H2O (k(H2O)~ 1 * 10(-15)
      cm(3) molec(-1) s(-1)) yields 73% hydroxymethyl hydroperoxide (HMHP), 6%
      formaldehyde + H2O2, and 21% formic acid + H2O; and CH2OO + (H2O)2 (k(H2O)2~ 1 *
      10(-12) cm(3) molec(-1) s(-1)) yields 40% HMHP, 6% formaldehyde + H2O2, and 54%
      formic acid + H2O. Competitive rate determinations (kSO2/k(H2O)n=1,2~ 2.2 (+/
      0.3) * 10(4)) and field observations suggest that water vapor is a sink for
      greater than 98% of CH2OO in a Southeastern US forest, even during pollution
      episodes ([SO2] ~ 10 ppb). The importance of the CH2OO + (H2O)n reaction is
      demonstrated by high HMHP mixing ratios observed over the forest canopy. We find
      that CH2OO does not substantially affect the lifetime of SO2 or HCOOH in the
      Southeast US, e.g., CH2OO + SO2 reaction is a minor contribution (<6%) to sulfate
      formation. Extrapolating, these results imply that sulfate production by
      stabilized Criegees is likely unimportant in regions dominated by the reactivity
      of ozone with isoprene. In contrast, hydroperoxide, organic acid, and
      formaldehyde formation from isoprene ozonolysis in those areas may be
      significant.

PMID- 27021603
TI  - Gene Therapy for Hemophilia.
AB  - Adeno-associated viral vectors have been developed for the treatment of
      hemophilia A and B. Derivation of vector particles is achieved after multiplasmid
      transfection of cells that package the vector genome to yield vector particles.
      To date, three clinical trials have been performed for hemophilia B. The results
      of these trials are described. The trial that we conducted with our collaborators
      has yielded evidence of clinical efficacy for hemophilia B. A vector for treating
      hemophilia A has been developed and a clinical trial is planned. 

PMID- 27021602
TI  - Transcriptome profile of the early stages of breast cancer tumoral spheroids.
AB  - Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to
      reliably mimic the initial growth of primary and metastatic cancer cells.
      However, cancer cell growth during the initial stages has not been fully explored
      using a genome-wide approach. Thus, in the present study, we investigated the
      transcriptome of breast cancer cells during the initial stages of tumoral growth
      using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses
      showed that a metastatic signature was enriched as several adhesion molecules
      were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which
      were further supported by an increase in cell migration. Interestingly, we also
      found that the cancer cells at this stage of growth exhibited a paradoxical
      hyperactivation of oxidative mitochondrial metabolism. In addition, we found a
      large number of regulated (long non coding RNA) lncRNAs, several of which were co
      regulated with neighboring genes. The regulatory role of some of these lncRNAs on
      mRNA expression was demonstrated with gain of function assays. This is the first
      report of an early-stage MTS transcriptome, which not only reveals a complex
      expression landscape, but points toward an important contribution of long non
      coding RNAs in the final phenotype of three-dimensional cellular models. 

PMID- 27021604
TI  - The Alarmin Properties of DNA and DNA-associated Nuclear Proteins.
AB  - PURPOSE: The communication of cell injury and death is a critical element in host
      defense. Although immune cells can serve this function by elaborating cytokines
      and chemokines, somatic cells can repurpose nuclear macromolecules to function as
      damage-associated molecular patterns (DAMPs) or alarmins to exert similar
      activity. Among these molecules, DNA, high-mobility group box-1, and histone
      proteins can all act as DAMPs once they are in an extracellular location. This
      review describes current information on the role of the nuclear DAMPs, their
      translocation to the outside of cells, and pathways of activation after uptake
      into the inside of immune cells. METHODS: MEDLINE and PubMed databases were
      searched for citations (1990-2016) in English related to the following terms:
      DAMPs, high-mobility group box-1, DNA, histones, cell death, danger, and immune
      activation. Selected articles with the most relevant studies were included for a
      more detailed consideration. FINDINGS: Although nuclear molecules have important
      structural and genetic regulatory roles inside the cell nucleus, when released
      into the extracellular space during cell death, these molecules can acquire
      immune activity and serve as alarmins or DAMPs. Although apoptosis is generally
      considered the source of extracellular nuclear material, other cell death
      pathways such as necroptosis, NETosis, and pyroptosis can contribute to the
      release of nuclear molecules. Importantly, the release of nuclear DAMPs occurs
      with both soluble and particulate forms of these molecules. The activity of
      nuclear molecules may depend on posttranslational modifications, redox changes,
      and the binding of other molecules. Once in an extracellular location, nuclear
      DAMPs can engage the same pattern recognition receptors as do pathogen-associated
      molecular patterns. These interactions can activate immune cells and lead to
      cytokine and chemokine production. Among these receptors, internal receptors for
      DNA are key to the response to this molecule; the likely function of these
      internal sensors is the recognition of DNA from intracellular infection by
      bacteria or viruses. Activation of these receptors requires translocation of
      extracellular DNA into specialized compartments. In addition to nuclear DNA,
      mitochondrial DNA can also serve as a DAMP. IMPLICATIONS: The communication of
      cell injury and death is a critical element in host defense and involves the
      repurposing of nuclear molecules as immune triggers. As such, the presence of
      extracellular nuclear material can serve as novel biomarkers for conditions
      involving cell injury and death. Targeting of these molecules may also represent
      an important new approach to therapy.

PMID- 27021605
TI  - Association of High Homocysteine Levels With the Risk Stratification in
      Hypertensive Patients at Risk of Stroke.
AB  - PURPOSE: We aimed to investigate the association between stroke morbidity and
      different stratifications of classic risk factors, such as increasing age, body
      mass index (BMI), blood lipids, and blood glucose, in hypertensive patients with
      high homocysteine levels. METHODS: A cross-sectional study of 2258 patients with
      primary hypertension were enrolled in this study, including 871 stroke cases
      (62.89%) in 1385 hypertensive patients without hyperhomocysteinemia (HHcy) and
      647 (74.11%) stroke cases in 873 hypertensive patients with HHcy. Basic
      information of patients were collected, including age, sex, height, weight,
      smoking, alcohol consumption, and disease history. Blood chemical assays were
      performed to determine the levels of glucose, triglycerides, high-density
      lipoprotein cholesterol (HDL-C), total cholesterol, and homocysteine.
      Subsequently, comparison of stroke morbidity between the 2 groups was performed
      after the stratification of risk factors. Moreover, the correlation between the
      stroke morbidity and the risk factors was analyzed using a trend test in patients
      with H-type hypertension. Univariate and multivariate logistic regression
      analyses were used to evaluate the association between baseline factors and
      prevalence of stroke in H-type hypertensive patients. FINDINGS: After the
      stratification of risk factors, a statistical difference was noted in age (range,
      45-74 yrs), glucose ranges (<6.1 and >=7.0 mmol/L), BMI, systolic blood pressure
      (SBP), diastolic blood pressure (DBP), non-HDL-C, and triglyceride level of <200
      mg/dL (P<0.05) in the H-type hypertension group compared with those in non-H-type
      hypertension group. Gradual elevation of stroke morbidity was identified with the
      increase of fasting glucose, SBP, and DBP. In multivariate logistic regression
      analysis, only higher SBP, DBP, fasting glucose level, homocysteine, and history
      of diabetes mellitus were the independent predictors for the stroke morbidity.
      IMPLICATIONS: Comprehensive evaluation and strict management of multiple risk
      factors have become increasingly important in the alleviation of stroke morbidity
      for H-type hypertensive patients because these patients were more sensitive to
      the classic risk factors.

PMID- 27021606
TI  - Single-dose Pharmacokinetic Properties and Relative Bioavailability of a Novel
      Methylphenidate Extended-release Chewable Tablet Compared With Immediate-release
      Methylphenidate Chewable Tablet.
AB  - PURPOSE: A novel methylphenidate hydrochloride extended-release chewable tablet
      (MPH ERCT) was developed to potentially address an unmet need for patients with
      attention-deficit/hyperactivity disorder, especially children, who cannot or will
      not swallow tablets or would prefer the convenience of a chewable tablet. This
      randomized, open-label, crossover trial compared the pharmacokinetic properties
      and relative bioavailability of MPH ERCT with an MPH chewable immediate-release
      tablet (IR MPH) formulation in healthy adults. METHODS: Healthy men and women 18
      to 55 years of age were randomly assigned to MPH ERCT 40 mg or 40 mg IR MPH
      administered in 2 equal doses of 20 mg 6 hours apart with a 7-day washout period.
      Plasma concentrations of MPH at selected time points up to 24 hours were
      measured, and pharmacokinetic parameters were determined using a noncompartmental
      approach in the SAS (Version 9.2) PROC general linear model procedure. FINDINGS:
      A total of 33 participants were enrolled in the study; 31 participants were
      included in the pharmacokinetic analysis. The exposure ratios for MPH ERCT and IR
      MPH (MPH ERCT/IR MPH) for area under the analyte concentration versus time curves
      (AUC) from time zero to the last measurable analyte concentration (AUC0-last)
      (87.64%; 95% CI, 84.96-90.41) and AUC0-infinity (89.11%; 95% CI, 86.57-91.73)
      were within the standard 80% to 125% bioequivalence acceptance criteria. Mean
      Cmax for MPH ERCT and IR MPH was 12.51 ng/mL and 15.57 ng/mL, respectively; mean
      time to Cmax was 4.16 hours and 6.43 hours, respectively. The mean Cmax of MPH
      ERCT was 80% of the Cmax of IR MPH due to a higher peak concentration that occurs
      after the second dose of IR MPH. All adverse events were mild in severity.
      IMPLICATIONS: The relative bioavailability of MPH ERCT 40 mg, based on the
      exposure (AUC), was comparable to that of IR MPH 40 mg administered in 2 equal
      doses of 20 mg 6 hours apart. Both formulations were generally well tolerated.

PMID- 27021607
TI  - Efficacy and Safety of Belimumab Plus Standard Therapy in Patients With Systemic
      Lupus Erythematosus: A Meta-analysis.
AB  - PURPOSE: The treatment of belimumab plus standard therapy in patients with
      systemic lupus erythematosus (SLE) has been studied extensively in recent years.
      Our aim was to estimate the efficacy and safety of this therapy compared with
      placebo plus standard therapy in patients with SLE. METHODS: PubMed, Web of
      Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), and
      Wanfang Database (Chinese) were searched for all randomized clinical trials that
      mainly studied the efficacy and safety of belimumab plus standard therapy before
      June 2015. We extracted or calculated the rate of the SLE Response Index and
      adverse event rate at 52 weeks in all the included studies. The odds ratio (OR)
      with 95% CI between the 2 groups in this meta-analysis was conducted by using a
      random-effects model. Sensitivity and publication bias analyses were also
      performed. All statistical tests were performed by using Stata software version
      12.0 (StataCorp., College Station, Texas). FINDINGS: In the overall samples (4
      studies, N = 4692 ), a significantly higher SLE Response Index rate at 52 weeks
      was found in belimumab plus standard therapy group compared with the placebo plus
      standard therapy group in all studies (OR = 1.49; 95% CI, 1.26-1.77 ; P < 0.001
      ). When assessed with the incidence of serious adverse events, the data revealed
      that there was no significant difference between the 2 groups, with pooled OR =
      1.08; 95% CI, 0.83-1.39; P = 0.573; OR = 1.23; 95% CI, 1.02-1.48; P = 0.029; and
      OR = 1.07; 95% CI, 0.88-1.29; P = 0.506. IMPLICATIONS: The results suggest that
      treatment with belimumab plus standard therapy is more effective than placebo
      plus standard therapy in SLE patients, which represents major progress in the
      treatment of SLE. Regardless of the statistical analyses, further research is
      necessary to optimize treatment effects.

PMID- 27021608
TI  - Efficacy and Safety of the SGLT2 Inhibitor Luseogliflozin in Japanese Patients
      With Type 2 Diabetes Mellitus Stratified According to Baseline Body Mass Index:
      Pooled Analysis of Data From 52-Week Phase III Trials.
AB  - PURPOSE: Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, may be
      beneficial in obese diabetic patients based on its potential to decrease blood
      glucose and body weight, but there is limited proof. This analysis aimed to
      investigate the efficacy and safety of luseogliflozin in patients with varying
      levels of obesity. METHODS: A pooled analysis of four 52-week Phase III trials of
      luseogliflozin 2.5 mg daily (or up to 5 mg daily) in Japanese patients with type
      2 diabetes mellitus stratified according to baseline body mass index (BMI) was
      conducted. Efficacy end points included changes in glycosylated hemoglobin
      (HbA1c), fasting plasma glucose (FPG), and body weight. FINDINGS: In total, 1031
      patients were included and stratified into 5 BMI (kg/m(2)) groups: low-to-medium
      (<22.5, n = 222); medium (>=22.5 to <25, n = 270); high-level 1 (>=25 to <27.5, n
      = 262); high-level 2 (>=27.5 to <30, n = 142); and very-high (>=30, n = 135).
      HbA1c decreased significantly compared with baseline until week 52 in all groups,
      and a similar trend was observed with FPG and body weight. The reduction in
      glycemic parameters tended to be slightly smaller in patients with BMI <22.5
      kg/m(2), and the reduction in body weight tended to be greater in patients with
      higher BMI, especially those with BMI >=30 kg/m(2). Levels of fasting insulin, C
      peptide immunoreactivity, triglyceride, blood pressure, aspartate
      aminotransferase, alanine aminotransferase, and uric acid decreased significantly
      at week 52 in all groups (except for aspartate aminotransferase in patients with
      BMI <22.5 kg/m(2)). Levels of these parameters tended to be higher at baseline
      and these enhanced levels resulted in a greater decrease in patients with higher
      BMI. In safety, the incidence of adverse events was similar between groups, and
      most of them were mild in severity. IMPLICATIONS: HbA1c and body weight decreased
      significantly in all groups. Decrease in glycemic parameters tended to be smaller
      in patients with BMI <22.5 kg/m(2), while that of body weight was larger in
      patients with higher BMI. Furthermore, luseogliflozin was especially beneficial
      in patients with higher BMI in terms of metabolic abnormalities, including
      insulin secretion and hypertension. Luseogliflozin exhibited a favorable and
      similar safety profile over 52 weeks in all groups. This agent can be an
      effective and well-tolerated therapeutic option in patients with a wide range of
      BMI levels, and it may be more beneficial in patients with higher BMI.

PMID- 27021609
TI  - Key Role of DAMP in Inflammation, Cancer, and Tissue Repair.
AB  - PURPOSE: This review aimed to take stock of the current status of research on
      damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced
      role of DAMP molecules in inflammation, cancer, and tissue repair. The high
      mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known
      DAMP molecules and have been primarily associated with inflammation. However, as
      we shall see, recent data have linked these molecules to tissue repair. HMGB1 is
      associated with cancer-related inflammation. It activates nuclear factor kB,
      which is involved in cancer regulation via its receptor for advanced glycation
      end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and
      tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and
      Toll like receptor 2 and 4 role in inflammation and by increasing their
      concentration in tissue repair, respectively. METHODS: We conducted a MEDLINE
      search for articles pertaining to the various issues related to DAMP, and we
      discuss the most relevant articles especially (ie, not only those published in
      journals with a higher impact factor). FINDINGS: A cluster of remarkable articles
      on DAMP have appeared in the literature in recent years. Regarding inflammation,
      several strategies have been proposed to target HMGB1, from antibodies to
      recombinant box A, which interacts with RAGE, competing with the full molecule.
      In tissue repair, it was reported that the overexpression of HMGB1 or the
      administration of exogenous HMGB1 significantly increased the number of vessels
      and promoted recovery in skin-wound, ischemic injury. IMPLICATIONS: Due to the
      bivalent nature of DAMP, it is often difficult to explain the relative role of
      DAMP in inflammation versus its role in tissue repair. However, this point is
      crucial as DAMP-related treatments move into clinical practice.

PMID- 27021610
TI  - Multi-indication Pharmacotherapeutic Multicriteria Decision Analytic Model for
      the Comparative Formulary Inclusion of Proton Pump Inhibitors in Qatar.
AB  - PURPOSE: The formulary inclusion of proton pump inhibitors (PPIs) in the
      government hospital health services in Qatar is not comparative or restricted.
      Requests to include a PPI in the formulary are typically accepted if evidence of
      efficacy and tolerability is presented. There are no literature reports of a PPI
      scoring model that is based on comparatively weighted multiple indications and no
      reports of PPI selection in Qatar or the Middle East. This study aims to compare
      first-line use of the PPIs that exist in Qatar. The economic effect of the study
      recommendations was also quantified. METHODS: A comparative, evidence-based
      multicriteria decision analysis (MCDA) model was constructed to follow the
      multiple indications and pharmacotherapeutic criteria of PPIs. Literature and an
      expert panel informed the selection criteria of PPIs. Input from the relevant
      local clinician population steered the relative weighting of selection criteria.
      Comparatively scored PPIs, exceeding a defined score threshold, were recommended
      for selection. FINDINGS: Weighted model scores were successfully developed, with
      95% CI and 5% margin of error. The model comprised 7 main criteria and 38
      subcriteria. Main criteria are indication, dosage frequency, treatment duration,
      best published evidence, available formulations, drug interactions, and
      pharmacokinetic and pharmacodynamic properties. Most weight was achieved for the
      indications selection criteria. Esomeprazole and rabeprazole were suggested as
      formulary options, followed by lansoprazole for nonformulary use. The estimated
      effect of the study recommendations was up to a 15.3% reduction in the annual PPI
      expenditure. Robustness of study conclusions against variabilities in study
      inputs was confirmed via sensitivity analyses. IMPLICATIONS: The implementation
      of a locally developed PPI-specific comparative MCDA scoring model, which is
      multiweighted indication and criteria based, into the Qatari formulary selection
      practices is a successful evidence-based cost-cutting exercise. Esomeprazole and
      rabeprazole should be the first-line choice from among the PPIs available at the
      Qatari government hospital health services.

PMID- 27021611
TI  - The relevance of muscle mass and quality to postoperative complications after
      open colon resection.

PMID- 27021612
TI  - A Minimally Invasive Surgical Approach to Synchronous Anal and Colon
      Adenocarcinoma: Review of Existing Literature.

PMID- 27021613
TI  - Searching for the Source Crater of Nakhlite Meteorites.
AB  - We surveyed the Martian surface in order to identify possible source craters of
      the nakhlite Martian meteorites. We investigated rayed craters that are assumed
      to be younger than 11 Ma, on lava surfaces with a solidification age around 1.2
      Ga. An area of 17.3 million km2 Amazonian lava plains was surveyed and 53 rayed
      craters were identified. Although most of them are smaller than the threshold
      limit that is estimated as minimum of launching fragments to possible Earth
      crossing trajectories, their observed size frequency distribution agrees with the
      expected areal density from cratering models characteristic for craters that are
      less than few tens of Ma old. We identified 6 craters larger than 3 km diameter
      constituting the potentially best source craters for nakhlites. These larger
      candidates are located mostly on a smooth lava surface, and in some cases, on the
      earlier fluvial-like channels. In three cases they are associated with fluidized
      ejecta lobes and rays - although the rays are faint in these craters, thus might
      be older than the other craters with more obvious rays. More work is therefore
      required to accurately estimate ages based on ray system for this purpose. A more
      detailed search should further link remote sensing Martian data with the in-situ
      laboratory analyses of Martian meteorites, especially in case of high altitude,
      steep terrains, where the crater rays seems to rarely survive several Ma.

PMID- 27021615
TI  - The effectiveness of lead glasses in reducing the doses to eye lenses during
      cardiac implantation procedures performed using x-ray tubes above the patient
      table.
AB  - The dose reduction factors (DRF) for different types of lead glasses and C-arm
      units with x-ray tubes placed above the patient table were calculated from the
      results of measurements by loose thermoluminescent dosimeters (TLDs) and EYE-D
      dosimeters using a Rando phantom. The DRF values were analysed for different
      positions of routine dosimeters worn outside lead eyewear and confronted with
      DRFs calculated as the ratio of the dose equivalent to the eye measured with and
      without the eyewear. Moreover, for eye lens dosimeters designed to be worn behind
      lead glasses, multiplicative factors for various positions of dosimeter were
      derived in order to account for the differences between the doses measured on the
      inner side of the glasses and the dose equivalent to the eye lens. The DRFs
      calculated for the position of a routine dosimeter worn outside lead glasses on
      the band near the left eye lens are 5.6 and 5.7 for goggles and metallic glasses,
      respectively, while the DRFs calculated as the ratio of doses to the eyes
      measured with and without the eyewear are 10.2 and 9.9, respectively. Therefore,
      for dosimeters routinely used outside lead eyewear, the DRF calculated for the
      position of the dosimeter should be used. Otherwise, we can anticipate an almost
      two-fold underestimation of the doses. When the dosimeter is worn behind lead
      glasses, up to two-fold differences between the dose equivalent to the eye lens
      and the dose measured at the inner side of the glasses were observed depending on
      the dosimeter position. 

PMID- 27021614
TI  - The potential effects of antioxidant feed additives in mitigating the adverse
      effects of corn naturally contaminated with Fusarium mycotoxins on antioxidant
      systems in the intestinal mucosa, plasma, and liver in weaned pigs.
AB  - Seventy-two piglets (6.0 kg BW) were randomly distributed within six different
      dietary treatments to evaluate the effect of deoxynivalenol (DON) and the
      potential of four antioxidant feed additives in mitigating the adverse effects of
      DON on growth performances and oxidative status. Dietary treatments were as
      follows: control diet 0.8 mg/kg DON; contaminated diet (DON-contaminated diet)
      3.1 mg/kg DON; and four contaminated diets, each supplemented with a different
      antioxidant feed additive, DON + vitamins, DON + organic selenium
      (Se)/glutathione (GSH), DON + quercetin, and DON + COMB (vitamins + Se/GSH +
      quercetin from the other treatments). Although DON was the main mycotoxin in the
      contaminated diet, this diet also contained 1.8 mg/kg of zearalenone (ZEN). The
      "mycotoxin" effects therefore included the combined effect of these two
      mycotoxins, DON, and ZEN. The DON-ZEN ingestion did not affect growth
      performances, average daily gain (ADG), average daily feed intake (ADFI), and
      feed efficiency (G:F ratio), but partially induced oxidative stress in weaned
      pigs as shown by increased malondialdehyde (MDA) content in the plasma and
      superoxide dismutase (SOD) activity in liver (P < 0.05). However, no change in
      the activity of other antioxidant enzymes or GSH concentrations was observed in
      plasma and liver of piglets fed the DON-contaminated diet (P > 0.05).
      Supplementation with individual antioxidant feed additive had a limited effect in
      weaned pigs fed DON-ZEN-contaminated diets. Combination of antioxidants (vitamins
      A, C, and E, quercetin, and organic Se/GSH) reduced plasma and liver MDA content
      and SOD activity in liver (P < 0.05) of piglets fed DON-ZEN-contaminated diets.
      Furthermore, this combination also reduced MDA content in the ileum (P < 0.05),
      although activity of glutathione peroxidases (GPx), SOD or catalase (CAT) in the
      ileum was not affected by DON-ZEN contamination or antioxidant supplements. In
      conclusion, DON-ZEN contamination induced oxidative stress in weaned pigs and
      combination of antioxidant feed additives restored partially the oxidative
      status. Further studies will be necessary to assess whether the effects of
      antioxidant feed additives on oxidative status are specific when feed is
      contaminated with DON-ZEN.

PMID- 27021616
TI  - Is there an optimal upper instrumented vertebra (UIV) tilt angle to prevent post
      operative shoulder imbalance and neck tilt in Lenke 1 and 2 adolescent idiopathic
      scoliosis (AIS) patients?
AB  - PURPOSE: To investigate whether an optimal upper instrumented vertebra (UIV) tilt
      angle would prevent 'lateral' shoulder imbalance or neck tilt (with 'medial'
      shoulder imbalance) post-operatively. METHODS: The mean follow-up for 60 AIS
      (Lenke 1 and Lenke 2) patients was 49.3 +/- 8.4 months. Optimal UIV tilt angle
      was calculated from the cervical supine side bending radiographs. Lateral
      shoulder imbalance was graded using the clinical shoulder grading. The clinical
      neck tilt grading was as follows: Grade 0: no neck tilt, Grade 1: actively
      correctable neck tilt, Grade 2: neck tilt that cannot be corrected by active
      contraction and Grade 3: severe neck tilt with trapezial asymmetry >1 cm. T1
      tilt, clavicle angle and cervical axis were measured. UIVDiff (difference between
      post-operative UIV tilt and pre-operative Optimal UIV tilt) and the reserve
      motion of the UIV were correlated with the outcome measures. Patients were
      assessed at 6 weeks and at final follow-up with a minimum follow-up duration of
      24 months. RESULTS: Among patients with grade 0 neck tilt, 88.2 % of patients had
      the UIV tilt angle within the reserve motion range. This percentage dropped to
      75.0 % in patients with grade 1 neck tilt whereas in patients with grade 2 and
      grade 3 neck tilt, the percentage dropped further to 22.2 and 20.0 % (p = 0.000).
      The occurrence of grade 2 and 3 neck tilt when UIVDiff was <5 degrees , 5-10
      degrees  and >10 degrees  was 9.5, 50.0 and 100.0 %, respectively (p = 0.005).
      UIVDiff and T1 tilt had a positive and strong correlation (r 2 = 0.618). However,
      UIVDiff had poor correlation with clavicle angle and the lateral shoulder
      imbalance. CONCLUSION: An optimal UIV tilt might prevent neck tilt with 'medial'
      shoulder imbalance due to trapezial prominence and but not 'lateral' shoulder
      imbalance.

PMID- 27021617
TI  - Do number of days with low back pain and patterns of episodes of pain have
      similar outcomes in a biopsychosocial prediction model?
AB  - PURPOSES: We used two different methods to classify low back pain (LBP) in the
      general population (1) to assess the overlapping of individuals within the
      different subgroups in those two classifications, (2) to explore if the
      associations between LBP and some selected bio-psychosocial factors are similar,
      regardless which of the two classifications is used. METHOD: During 1 year, 49-
      or 50-year-old people from the Danish general population were sent fortnightly
      automated text messages (SMS-Track) asking them if they had any LBP in the past
      fortnight. Responses for the whole year were then classified into two different
      ways: (1) In relation to the number of days with LBP in the preceding year (0, 1
      30, and >30), (2) In relation to the frequency and duration of episodes of LBP
      (more or less never pain, episodic, and more or less constant pain). Some bio
      psychosocial factors, collected with a questionnaire at baseline 9 years earlier,
      were entered into regression models to investigate their associations with the
      subgroups of the two classifications of LBP and the results compared. RESULTS:
      The percentage of agreement between categories of the two classification systems
      was above 68 % (Kappa 0.7). Despite the large overlap of persons in the two
      classification groups, the patterns of associations with the two types of LBP
      definitions were different in the two classification groups. However, none of the
      estimates were significantly different when the variables were compared across
      the two classifications. CONCLUSION: Different classification systems of LBP are
      capable of bringing forth different findings. This may help explain the lack of
      consistency between studies on risk factors of LBP.

PMID- 27021618
TI  - A comparative study on the accuracy of pedicle screw placement assisted by
      personalized rapid prototyping template between pre- and post-operation in
      patients with relatively normal mid-upper thoracic spine.
AB  - PURPOSE: The aim of this study was to assess the accuracy of rapid prototyping
      drill template technique for placing pedicle screws in the mid-upper thoracic
      vertebrae in clinics. METHODS: 151 consecutive patients underwent thoracic
      instrumentation and fusion for a total of 582 pedicle screws placed in the mid
      upper thoracic vertebrae. Using computer software, the authors constructed drill
      templates that fit onto the posterior elements of the mid-upper thoracic
      vertebrae with drill guides designed to instrument the pedicles. The start point
      and three dimensional location of the planned and inserted screws were measured
      and compared. RESULTS: Grading of the CT scans revealed 559 (96.1 %) out of 582
      screws completely within the desired pedicle. The direction of pedicle violation
      included 5 medial, 2 airball, and 16 lateral. The paired t test suggested that
      these results were statistically significant in more than half of the locations
      (T1-left-TA(P = 0.024), T2-left-SA(P = 0.031), T3-left-SA(P = 0.014), T4-left
      TA(P = 0.004), T5-left-TA(P = 0.034), T7-left-TA(P = 0.000). T1-right-TA(P =
      0.049), T2-right-TA(P = 0.044), T3-right-TA(P = 0.014), T5-right-TA(P = 0.013)).
      The paired t-test suggested that these results were statistically significant at
      several locations (T4-left-Deltay(P = 0.041), T5-left-Deltax(P = 0.016), T3-right
      Deltay(P = 0.015)). CONCLUSION: Use of a rapid prototyping drill template to
      assist in the placement of mid and upper thoracic pedicle screws may lead to
      increased accuracy. This patient specific technology must be combined with an
      understanding of the patients' anatomy and carefully secured to the posterior
      elements intraoperatively to avoid nerve or vascular complications.

PMID- 27021619
TI  - Transcatheter Aortic Valve Implantation.
AB  - Severe aortic stenosis (AS) is a life-threatening condition when left untreated.
      Aortic valve replacement (AVR) is the gold standard treatment for the majority of
      patients; however, transcatheter aortic valve implantation/replacement
      (TAVI/TAVR) has emerged as the preferred treatment for high-risk or inoperable
      patients. The concept of transcatheter heart valves originated in the 1960s and
      has evolved into the current Edwards Sapien and Medtronic CoreValve platforms
      available for clinical use. Complications following TAVI, including
      cerebrovascular events, perivalvular regurgitation, vascular injury, and heart
      block have decreased with experience and evolving technology, such that ongoing
      trials studying TAVI in lower risk patients have become tenable. The
      multidisciplinary team involving the cardiac surgeon and cardiologist plays an
      essential role in patient selection, procedural conduct, and perioperative care. 

PMID- 27021620
TI  - Spontaneous haematoma of the anterior rectus abdominis muscle.
AB  - INTRODUCTION: Spontaneous haematoma of the rectus abdominis muscle is an uncommon
      cause of abdominal pain. It occurs mostly in anticoagulated patients. The
      objective of this paper is to analyse the onset, diagnosis and treatment in
      patients under anticoagulant therapy. METHODS: A retrospective analysis of a
      prospectively maintained database of all patients with a diagnosis of spontaneous
      hematoma of the abdominal rectus muscle between March 2003 and December 2014.
      RESULTS: The study included 34 patients, of whom 28 were women, with an average
      age of 80 years old. All the patients showed a unilateral infraumbilical
      haematoma. Twenty- 8 patients had received long-term anticoagulant treatment (26
      with acenocumarol and 2 low molecular weight heparin); and 6 patients were under
      anticoagulant prophylaxis with low molecular weight heparin. The diagnosis was
      performed with ultrasound in 7 cases, computed tomography angiography in 27
      patients, and with both methods in 6 cases. The treatment consisted of stopping
      the anticoagulant drug, correcting haemostasis parameters and blood transfusion
      when required. Ten patients displayed active bleeding in the computed tomography
      angiography, and 8 underwent selective arterial embolization. The evolution was
      successful in 34 patients, however, 2 patients required surgery and, finally,
      died due to persistent haemorrhage. CONCLUSION: Spontaneous haematoma of the
      rectus abdominis muscle is more frequent in elderly women under oral
      anticoagulant treatment. Non-operative treatment is successful in most cases.
      Computed tomography angiography is useful to determine which patients could
      benefit from selective arterial embolization.

PMID- 27021621
TI  - A cuckoo-like parasitic moth leads African weaver ant colonies to their ruin.
AB  - In myrmecophilous Lepidoptera, mostly lycaenids and riodinids, caterpillars trick
      ants into transporting them to the ant nest where they feed on the brood or, in
      the more derived "cuckoo strategy", trigger regurgitations (trophallaxis) from
      the ants and obtain trophic eggs. We show for the first time that the
      caterpillars of a moth (Eublemma albifascia; Noctuidae; Acontiinae) also use this
      strategy to obtain regurgitations and trophic eggs from ants (Oecophylla
      longinoda). Females short-circuit the adoption process by laying eggs directly on
      the ant nests, and workers carry just-hatched caterpillars inside. Parasitized
      colonies sheltered 44 to 359 caterpillars, each receiving more trophallaxis and
      trophic eggs than control queens. The thus-starved queens lose weight, stop
      laying eggs (which transport the pheromones that induce infertility in the
      workers) and die. Consequently, the workers lay male-destined eggs before and
      after the queen's death, allowing the colony to invest its remaining resources in
      male production before it vanishes. 

PMID- 27021622
TI  - Comparison of automated erythrocytapheresis versus manual exchange transfusion to
      treat cerebral macrovasculopathy in sickle cell anemia.
AB  - BACKGROUND: Chronic exchange transfusion is effective for primary and secondary
      prevention of stroke in children with sickle cell anemia (SCA).
      Erythrocytapheresis is recognized to be the most efficient approach; however, it
      is not widely implemented and is not suitable for all patients. The aim of our
      study was to compare automated exchange transfusion (AET) with our manual method
      of exchange transfusion and, in particular, to evaluate the efficacy, safety, and
      cost of our manual method. STUDY DESIGN AND METHODS: Thirty-nine SCA children
      with stroke and/or abnormal findings on transcranial Doppler were included in the
      study. We retrospectively analyzed 1353 exchange sessions, including 333 sessions
      of AET and 1020 sessions of manual exchange transfusion (MET). RESULTS: Both
      methods were well tolerated. The median decrease in hemoglobin (Hb)S per session
      was 21.5% with AET and 18.8% with our manual method (p < 0.0001) with no major
      increase in red blood cell consumption. Iron overload was well controlled, even
      with the manual method, with a median (interquartile range) ferritin level of 312
      (152-994) ug/L after 24 months of transfusions. The main differences in annual
      cost relate to equipment costs, which were 74 times higher with the automated
      method. CONCLUSION: Our study shows that continuous MET has comparable efficacy
      to the automated method in terms of stroke prevention, decrease in HbS, and iron
      overload prevention. It is feasible in all hospital settings and is often
      combined with AET successively over time.

PMID- 27021623
TI  - Identification of WD40 repeats by secondary structure-aided profile-profile
      alignment.
AB  - A WD40 protein typically contains four or more repeats of ~40 residues ended with
      the Trp-Asp dipeptide, which folds into beta-propellers with four beta strands in
      each repeat. They often function as scaffolds for protein-protein interactions
      and are involved in numerous fundamental biological processes. Despite their
      important functional role, the "velcro" closure of WD40 propellers and the
      diversity of WD40 repeats make their identification a difficult task. Here we
      develop a new WD40 Repeat Recognition method (WDRR), which uses predicted
      secondary structure information to generate candidate repeat segments, and
      further employs a profile-profile alignment to identify the correct WD40 repeats
      from candidate segments. In particular, we design a novel alignment scoring
      function that combines dot product and BLOSUM62, thereby achieving a great
      balance of sensitivity and accuracy. Taking advantage of these strategies, WDRR
      could effectively reduce the false positive rate and accurately identify more
      remote homologous WD40 repeats with precise repeat boundaries. We further use
      WDRR to re-annotate the Pfam families in the beta-propeller clan (CL0186) and
      identify a number of WD40 repeat proteins with high confidence across nine model
      organisms. The WDRR web server and the datasets are available at
      http://protein.cau.edu.cn/wdrr/.

PMID- 27021624
TI  - Assessment of factors enabling halite formation in a marsh in a humid temperate
      climate (Ajo Marsh, Argentina).
AB  - The formation of evaporites associated with the final stages of the precipitation
      sequence, such as the case of halite, is frequent in marshes in arid areas, but
      it is not to be expected in those humid climates. This work, by means of the
      study of the hydrological, climatic and land use conditions, identifies the
      factors that allow the formation of saline precipitations in a marsh located in a
      humid climate area. The results obtained show that the exclusion of the marsh as
      a result of the embankment is the main reason for the presence of halite. It is
      to be expected that in the future the growth of the embanked marsh areas,
      together with the climatic and tidal condition tendencies recorded, will favour a
      higher rate of formation of evaporite salts. The identification of these factors
      makes it possible to set basic sustainable management guidelines to avoid soil
      salinisation. 

PMID- 27021625
TI  - Spatial variability in persistent organic pollutants and polycyclic aromatic
      hydrocarbons found in beach-stranded pellets along the coast of the state of Sao
      Paulo, southeastern Brazil.
AB  - High spatial variability in polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs), organochlorine pesticides, such as DDTs, and
      polybrominated diphenylethers was observed in plastic pellets collected randomly
      from 41 beaches (15 cities) in 2010 from the coast of state of Sao Paulo,
      southeastern Brazil. The highest concentrations ranged, in ng g(-1), from 192 to
      13,708, 3.41 to 7554 and <0.11 to 840 for PAHs, PCBs and DDTs, respectively.
      Similar distribution pattern was presented, with lower concentrations on the
      relatively less urbanized and industrialized southern coast, and the highest
      values in the central portion of the coastline, which is affected by both waste
      disposal and large port and industrial complex. Additional samples were collected
      in this central area and PCB concentrations, in ngg(-)(1), were much higher in
      2012 (1569 to 10,504) than in 2009/2010 (173 to 309) and 2014 (411), which is
      likely related to leakages of the PCB commercial mixture. 

PMID- 27021627
TI  - American dental hygienists' attitudes towards chairside medical screening in a
      dental setting.
AB  - OBJECTIVES: Targeted screening for medical conditions in a dental setting can be
      an effective strategy for early identification of individuals at increased
      disease risk. Dentists, patients and physicians have a favourable attitude
      towards this strategy. Given that dental hygienists (DHs) are involved in
      preventive and educational activities, this seems like a natural extension to
      their roles. We report on the attitudes of American DHs towards chairside medical
      screening. METHODS: A 5-point Likert scale (1 = very important/willing, 5 = very
      unimportant/unwilling) survey was mailed to a nationwide random sample of US
      practicing DHs. Descriptive statistics were used for all questions, and the
      Friedman nonparametric analysis of variance was used for multi-element questions.
      RESULTS: A total of 3133 respondents returned the completed questionnaires for an
      effective response rate of 49.2% and a margin of error 1.8%. The majority of
      respondents felt it was important to perform/conduct chairside screening for
      hypertension (94%), diabetes mellitus (89%), cardiovascular disease (85%), HIV
      (79%) and hepatitis infection (78%); were willing to refer a patient for medical
      consult (94%), conduct screening that yields immediate results (85%); and were
      willing to collect the data/samples needed (57-95%). The most important
      considerations were dentist/owner support (98%), training (97%), patient
      willingness (98%) and time (98%). CONCLUSION: Similar to dentists, physicians and
      patients, the majority of the DHs had a favourable attitude towards chairside
      medical screening. Integrating the DH into screening activities is likely to
      require additional training and education regarding the diseases of interest,
      something that could be accomplished through continuing education courses and
      eventually incorporation into the educational curriculum.

PMID- 27021626
TI  - S100A9 and ORM1 serve as predictors of therapeutic response and prognostic
      factors in advanced extranodal NK/T cell lymphoma patients treated with
      pegaspargase/gemcitabine.
AB  - Pegaspargase combined with gemcitabine have greatly improved the outcomes of
      advanced extranodal NK/T cell lymphoma (ENKL). However, patients frequently
      undergo recurrent disease due to chemoresistance, and few predictive parameters
      are available. The present study explored potential biomarkers to predict the
      therapeutic response of advanced ENKL treated with pegaspargase/gemcitabine and
      evaluate the prognostic significance. Through serum proteomic analysis, we
      identified 61 upregulated and 22 downregulated proteins in nonresponders compared
      with responders. We further validated that patients with unfavourable treatment
      outcomes displayed higher levels of S100A9 and ORM1 via enzyme-linked
      immunosorbent assay (ELISA). Moreover, the sensitivity and specificity for
      detecting refractory patients were 81.5% and 71.4% for S100A9 > 62 ng/ml, 85.2%
      and 77.1% for ORM1 > 1436 ug/ml, 100% and 57.1% for S100A9 combined with ORM1.
      Furthermore, in multivariate analysis elevated levels of S100A9 were associated
      with poor 2-year OS (40.2% vs. 76.6%, RR = 2.92, p = 0.005) and 2-year PFS (33.1%
      vs. 61.1%, RR = 2.61 p = 0.011). High ORM1 also predicted inferior 2-year OS
      (38.7% vs.76.1, RR = 2.46, p = 0.023) and 2-year PFS (18.4% vs. 73.2%, RR = 2.86,
      p = 0.009). Our results indicated that S100A9 and ORM1 could serve as reliable
      predictors of therapeutic response and independent prognostic factors of survival
      in advanced ENKL patients treated with pegaspargase/gemcitabine.

PMID- 27021628
TI  - A mesoporous nanocontainer gated by a stimuli-responsive peptide for selective
      triggering of intracellular drug release.
AB  - Mesoporous silica nanocontainers (MSNs) with biologically responsive gatekeepers
      have great potential for effective delivery of cargo molecules to the desired
      sites. For that purpose, peptides could be effective candidates as gatekeepers
      because of their bioresponsiveness and targeting capability. Taking advantage of
      the zinc finger domain peptide (CXXC), we designed a biocompatible all-peptide
      gatekeeper (WCGKC) with on-off gatekeeping capability through stimulus-responsive
      conformational conversion and the steric bulkiness of the tryptophan unit. The
      turn structure induced by an intramolecular disulfide bond of the peptide
      gatekeeper (WCGKC-SS) completely inhibited the release of the entrapped
      doxorubicin (DOX). However, upon reduction of the disulfide bond by glutathione
      (GSH), the peptide conformation was converted to a random structure, which opened
      the orifice of the mesopore leading to the release of DOX. The amine moiety of
      the lysine of the peptide gatekeeper was PEGylated to enhance dispersion
      stability and biocompatibility of the nanocontainer. Furthermore, the MSNs with
      the peptide gatekeeper (PEG-WCGKC-SS-Si) selectively released the entrapped DOX
      in A549 human lung cancer cells in a controlled manner triggered by intracellular
      GSH, but not in CCD normal lung cells containing a low intracellular GSH level.
      In A549 cells, DOX-loaded PEG-WCGKC-SS-Si exhibited about 10-times higher
      cytotoxicity induced by apoptosis than that in CCD cells. 

PMID- 27021630
TI  - Parallel NMR spectroscopy with simultaneous detection of (1) H and (19) F nuclei.
AB  - Recording NMR signals of several nuclear species simultaneously by using parallel
      receivers provides more information from a single measurement and at the same
      time increases the measurement sensitivity per unit time. Here we present a
      comprehensive series of the most frequently used NMR experiments modified for
      simultaneous direct detection of two of the most sensitive NMR nuclei - (1) H and
      (19) F. We hope that the presented material will stimulate interest in and
      further development of this technique. 

PMID- 27021629
TI  - DNA-based taxonomic identification of basidiospores in hallucinogenic mushrooms
      cultivated in "grow-kits" seized by the police: LC-UV quali-quantitative
      determination of psilocybin and psilocin.
AB  - The taxonomic identification of the biological material contained in the
      hallucinogenic mushrooms culture media, was carried out using a DNA-based
      approach, thus highlighting the usefulness of this approach in the forensic
      identification of illegal samples also when they are present as basidiospores
      mixed in culture media and spore-bearing fruiting body are not present. This
      approach is very useful as it allows the unequivocal identification of
      potentially illicit material before the cultivation and it enables to stop the
      material to the Customs and to destroy it due to its dangerousness without
      cultivating the "grow-kits" and without instructing a criminal case. In fact,
      even if psilocin and psilocybin and the whole mushrooms are illegal in many
      countries, there is no specific indication in the law about the so called "grow
      kits", containing the spores. To confirm the data obtained by the taxonomic
      identification, a simple, reliable, efficient LC-UV method, using tryptamine as
      internal standard, suitable for the forensic quali-quantitative determination of
      psilocin and psilocybin in hallucinogenic mushroom was optimized, validated and
      applied to the mushrooms grown after the cultivation of the grow-kits seized by
      the judicial authority, with the authorization of the Ministry of Health. A
      cation exchange column was used in a gradient elution mode (Phase A: 50mMK2HPO4;
      100mM NaCl pH=3 Phase B: methanol). The developed method was linear over the
      calibration range with a R(2)>0.9992 for both the analytes. The detection and
      quantification limits were respectively 0.01 and 0.1MUg/mL for psilocybin and
      0.05MUg/mL and 0.1MUg/mL for psilocin and the intra- and inter-day precision was
      satisfactory (coefficients of variation <2.0% for both the analytes). The content
      of psilocybin in the mushrooms grown from the seized "grow-kits" ranged from 1.02
      to 7.60mg/g of dry vegetable material, while the content of psilocin from 0.415
      to 8.36mg/g. 

PMID- 27021631
TI  - EDTA-treated cotton-thread microfluidic device used for one-step whole blood
      plasma separation and assay.
AB  - This study aims to observe the wicking and separation characteristics of blood
      plasma in a cotton thread matrix functioning as a microfluidic thread-based
      analytical device (MUTAD). We investigated several cotton thread treatment
      methods using ethylenediaminetetraacetic acid (EDTA) anticoagulant solution for
      wicking whole blood samples and separating its plasma. The blood of healthy
      Indonesian thin tailed sheep was used in this study to understand the properties
      of horizontal wicking and separation on the EDTA-treated MUTAD. The wicking
      distance and blood cell separation from its plasma was observed for 120 s and
      documented using a digital phone camera. The results show that untreated cotton
      threads stopped the blood wicking process on the MUTAD. On the other hand, the
      deposition of EDTA anticoagulant followed by its drying on the thread at room
      temperature for 10 s provides the longest blood wicking with gradual blood plasma
      separation. Furthermore, the best results in terms of the longest wicking and the
      clearest on-thread separation boundary between blood cells and its plasma were
      obtained using the MUTAD treated with EDTA deposition followed by 60 min drying
      at refrigerated temperature (2-8  degrees C). The separation length of blood
      plasma in the MUTADs treated with dried-EDTA at both room and refrigerated
      temperatures was not statistically different (P > 0.05). This separation occurs
      through the synergy of three factors, cotton fiber, EDTA anticoagulant and blood
      platelets, which induce the formation of a fibrin-filter via a partial
      coagulation process in the EDTA-treated MUTAD. An albumin assay was employed to
      demonstrate the efficiency of this plasma separation method during a one-step
      assay on the MUTAD. Albumin in blood is an important biomarker for kidney and
      heart disease. The MUTAD has a slightly better limit of detection (LOD) than
      conventional blood analysis, with an LOD of 114 mg L(-1) compared to 133 mg L(
      1), respectively. However, the MUTAD performed faster to get results after 3 min
      compared to 14 min for centrifuged analysis of sheep blood samples. In
      conclusion, on-thread dried-EDTA anticoagulant deposition was able to increase
      the wicking distance and has a better capability to separate blood plasma and is
      suitable for combining separation and the assay system in a single device. 

PMID- 27021632
TI  - Procedures to Assist Health Care Providers to Determine When Home Assessments for
      Potential Mold Exposure Are Warranted.
AB  - Drawing evidence from epidemiology and exposure assessment studies and
      recommendations from expert practice, we describe a process to guide health care
      providers helping their patients who present with symptoms that might be
      associated with living in damp housing. We present the procedures in the form of
      a guided 2-part interview. The first part has 5 questions that triage the patient
      toward a more detailed questionnaire that reflects features of housing conditions
      known to be reliably associated with exposures to mold and dampness contaminants.
      We chose the questions based on the conditions associated with moisture problems
      in homes across the United States and Canada. The goal is to facilitate the
      clinician's effort to help patients reduce exposure to environmental triggers
      that elicit symptoms to better manage their disease.

PMID- 27021633
TI  - Lung Sound Analysis and Airway Inflammation in Bronchial Asthma.
AB  - BACKGROUND: Our previous study on lung sound analysis (LSA) revealed that the
      expiration-to-inspiration sound power ratio in a low-frequency range (E/I LF) was
      increased in patients with bronchial asthma, even when they have no wheezes.
      OBJECTIVE: We also monitored the expiration-to-inspiration sound power ratio in a
      mid-frequency range (E/I MF) and the mid- to low-frequency sound power ratio for
      inspiration and expiration (ie, I MF/LF and E MF/LF, respectively) using a new
      software program to examine which parameter is most suitable as an index of
      airway inflammation in patients with asthma. METHODS: A study was conducted in 31
      patients with mild-to-moderate bronchial asthma to examine potential correlations
      of LSA parameters (E/I LF, E/I MF, I MF/LF, and E MF/LF) with spirogram
      parameters, airway hyperresponsiveness (PC20), fractional exhaled nitric oxide
      (NO), and sputum eosinophils. RESULTS: E/I LF was significantly correlated with
      airway narrowing (forced expiratory volume in 1 second [FEV1.0]/forced vital
      capacity [FVC]%: r = -0.50, maximal expiratory flow at 50% [V50],%pred: r = 
      0.50) and peripheral airway inflammation (alveolar NO: r = 0.36, eosinophils in
      peripheral sputum: r = 0.41). E/I MF was significantly correlated with airway
      narrowing (FEV1.0/FVC%: r = -0.46, V50,%pred: r = -0.49), airway inflammation
      (bronchial NO: r = 0.43, alveolar NO: r = 0.47, eosinophils in peripheral sputum:
      r = 0.50), and airway hyperresponsiveness (logPC20: r = -0.49). E MF/LF was
      significantly correlated with airway inflammation (NO: r = 0.36, eosinophils in
      sputum: r = 0.40) and airway hyperresponsiveness (logPC20: r = -0.40). I MF/LF
      was not significantly correlated with any parameters. CONCLUSIONS: Among the 4
      LSA parameters investigated, E/I MF demonstrated the highest correlation with
      airway inflammation, and also with bronchial hyperresponsiveness.

PMID- 27021634
TI  - Force in the Scapholunate Interosseous Ligament During 2 Simulated Pushup
      Positions.
AB  - PURPOSE: To determine the in vitro force between the scaphoid and the lunate
      supported by the scapholunate interosseous ligament (SLIL) during 2 wrist pushup
      positions. METHODS: Six fresh-frozen cadaveric wrists were tested in a neutral
      flexion-extension (knuckle) pushup position and in an extended pushup position.
      Tensile forces were measured across the scapholunate joint as half body weight
      axial forces were applied through the radius and ulna. Forces were measured after
      sectioning the SLIL, after also sectioning the dorsal radiocarpal and dorsal
      intercarpal ligaments, and then after also sectioning the radioscaphocapitate
      ligament. RESULTS: In the neutral position with the SLIL sectioned, the tensile
      force across the scapholunate joint was significantly larger in the extended
      position (45 N) than in the neutral position (25 N). Sectioning additional
      ligaments did not significantly increase the measured force. Extrapolation of the
      measured force in wrist extension with application of 1 time body weight suggests
      a force of 110 N would occur in the SLIL. CONCLUSIONS: This study demonstrated
      that, with the SLIL sectioned, with or without the dorsal radiocarpal, dorsal
      intercarpal, and radioscaphocapitate ligaments sectioned, the tensile force
      across the scapholunate joint is greater in extension than in the neutral wrist
      position. CLINICAL RELEVANCE: This study helps characterize the forces
      experienced across the scapholunate articulation when the SLIL is disrupted.

PMID- 27021635
TI  - Wrist Arthrodesis for Failed Total Wrist Arthroplasty.
AB  - PURPOSE: Treatment options for failed total wrist arthroplasty include implant
      revision, resection arthroplasty, and arthrodesis. Variable results associated
      with different techniques have been reported for arthrodesis and the procedure
      has substantial technical challenges, including restoration of wrist height,
      obtaining stable fixation, and achieving bony fusion. This study evaluates the
      radiographic results of a surgical technique for conversion of a failed
      arthroplasty to an arthrodesis. METHODS: A retrospective chart and radiograph
      review was performed in 20 wrists in 18 patients in whom conversion to an
      arthrodesis was performed using a contoured cancellous femoral head structural
      allograft and a wrist arthrodesis plate. Supplemental demineralized bone matrix
      combined with corticocancellous allograft chips was also used in 15 wrists.
      Median age at arthrodesis was 61 years (range, 45-78 years), and median follow-up
      was 34 months (range, 4-71 months). RESULTS: Nineteen of 20 wrists fused
      following the index procedure at a median of 4 months (range, 3-7 months).
      Proximal plate loosening occurred in 1 wrist but the joint still fused at 6
      months; a successful osteotomy and revision of screw fixation was done 2 years
      later to correct the deformity and hardware irritation in this case.
      Complications were otherwise limited to 1 superficial infection that resolved
      with intravenous antibiotics. CONCLUSIONS: This technique for conversion of a
      failed total wrist arthroplasty to a wrist arthrodesis is safe, effective, and
      versatile. Wrist deformity is corrected, wrist height can be restored, stable
      fixation is obtained, and a high rate of fusion is achieved despite filling large
      defects using structural cancellous allograft. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 27021636
TI  - The Detrimental Effect of Decentralization in Digital Replantation in the United
      States: 15 Years of Evidence From the National Inpatient Sample.
AB  - PURPOSE: Recent reports suggest a decrease in success rates in digital
      replantation in the United States. We hypothesize that this decrease may be
      associated with decentralization of replants away from high-volume hospitals.
      METHODS: All amputation injuries and digital replants captured by the National
      Inpatient Sample during 1998 to 2012 were identified. Procedures were
      characterized as occurring at high-volume hospitals (> 20 replants/y), and as
      being performed by high-volume surgeons (> 5 replants/y). A successful procedure
      was defined as one in which a replantation occurred without a subsequent revision
      amputation. Hospital and surgeon volume were tested for association with the year
      and the success of the procedure. RESULTS: The authors identified 101,693
      amputation injuries resulting in 15,822 replants. The overall success of replants
      dropped from 74.5% during 2004 to 2006 to 65.7% during 2010 to 2012. The
      percentage of replants being performed at high-volume hospitals decreased from
      15.5% during 2004 to 2006 to 8.9% during 2007 to 2009. Similarly, the percentage
      of replants being performed by high-volume surgeons decreased from 14.4% during
      1998 to 2000 to 2.6% during 2007 to 2009. Replants performed by high-volume
      surgeons operating at high-volume hospitals had higher success rates than low
      volume surgeons operating at low-volume hospitals (92.0% vs 72.1%). In addition,
      high-volume surgeons operating at high-volume hospitals attempted replantation at
      greater rates than low-volume surgeons operating at low-volume hospitals (21.5%
      vs 11.0%). Overall, an amputation injury presenting to a high-volume surgeon at a
      high-volume center had a 2.5 times greater likelihood of obtaining a successful
      replantation than an amputation injury presenting to a low-volume surgeon at a
      low-volume hospital. CONCLUSIONS: These data suggest that decreased success rates
      of digital replantation in the United States are correlated with the
      decentralization of digital replantation away from high-volume hospitals.
      CLINICAL RELEVANCE: The establishment of regional centers for replant referral
      may greatly increase the success of digital replantation in the United States.

PMID- 27021637
TI  - Mouse bone marrow stromal cells differentiate to neuron-like cells upon
      inhibition of BMP signaling.
AB  - Bone marrow stromal cells (BMSCs) are a source of autologous stem cells that have
      the potential for undergoing differentiation into multiple cell types including
      neurons. Although the neuronal differentiation of mesenchymal stem cells has been
      studied for a long time, the molecular players involved are still not defined.
      Here we report that the genetic deletion of two members of the bone morphogenetic
      protein (Bmp) family, Bmp2 and Bmp4 in mouse BMSCs causes their differentiation
      into cells with neuron-like morphology. Surprisingly these cells expressed
      certain markers characteristic of both neuronal and glial cells. Based on this
      observation, we inhibited BMP signaling in mouse BMSCs through a brief exposure
      to Noggin protein which also led to their differentiation into cells expressing
      both neuronal and glial markers. Such cells seem to have the potential for
      further differentiation into subtypes of neuronal and glial cells and thus could
      be utilized for cell-based therapeutic applications.

PMID- 27021638
TI  - Poly (ADP-ribose) polymerase1 regulates growth and multicellularity in D.
      discoideum.
AB  - Poly (ADP-ribose) polymerase (PARP)-1 regulates various biological processes like
      DNA repair, cell death etc. However, the role of PARP-1 in growth and
      differentiation still remains elusive. The present study has been undertaken to
      understand the role of PARP-1 in growth and development of a unicellular
      eukaryote, Dictyostelium discoideum. In silico analysis demonstrates ADPRT1A as
      the ortholog of human PARP-1 in D. discoideum. The present study shows that
      ADPRT1A overexpression (A OE) led to slow growth of D. discoideum and significant
      population of AOE cells were in S and G2/M phase. Also, AOE cells exhibited high
      endogenous PARP activity, significant NAD(+) depletion and also significantly
      lower ADPRT1B and ADPRT2 transcript levels. Moreover, AOE cells are intrinsically
      stressed and also exhibited susceptibility to oxidative stress. AOE also affected
      development of D. discoideum predominantly streaming, aggregation and formation
      of early culminant which are concomitant with reports on PARP's role in D.
      discoideum development. In addition, under developmental stimuli, increased PARP
      activity was seen along with developmentally regulated transcript levels of
      ADPRT1A during D. discoideum multicellularity. Thus the present study suggests
      that PARP-1 regulates growth as well as the developmental morphogenesis of D.
      discoideum, thereby opening new avenues to understand the same in higher
      eukaryotes.

PMID- 27021639
TI  - Magnetic field contributes to the cellular uptake for effective therapy with
      magnetofection using plasmid DNA encoding against Mcam in B16F10 melanoma in
      vivo.
AB  - AIM: We explored the distribution and cellular uptake of intratumorally injected
      SPIONs-PAA-PEI-pDNA (magnetofection complexes), and antitumor effectiveness of
      magnetofection with plasmid DNA encoding short hairpin RNA (shRNA) against Mcam
      (pDNA(anti-MCAM)). MATERIALS & METHODS: Analyses were made based on the
      histology, ultrastructure and quantitative measurements of magnetofection
      complexes, and quantification of the antitumor effectiveness in B16F10 melanoma
      in vivo. RESULTS: Injected magnetofection complexes were distributed around the
      injection site. Exposure of tumors to external magnetic field contributed to the
      uptake of magnetofection complexes from extracellular matrix into melanoma cells.
      Three consecutive magnetofections of tumors with pDNA(anti-MCAM) resulted in
      significant reduction of tumor volume. CONCLUSION: Magnetofection is effective
      for gene delivery to melanoma tumors, but requires a magnetic field for cellular
      uptake and antitumor effect.

PMID- 27021641
TI  - Vascular Anatomy of the Cauda Equina and Its Implication on the Vascular Lesions
      in the Caudal Spinal Structure.
AB  - The cauda equina is composed of the lumbosacral and the coccygeal nerve roots and
      the filum terminale. In the embryonic period, discrepancy in development between
      the termination of the spinal cord and the spinal column results in elongation of
      the nerve roots as well as the filum terminale in this region. Although the
      vascular anatomy of the caudal spinal structure shares many common features with
      the other metameric levels, this elongation forms the basis of the characteristic
      vascular anatomy in this region. With the evolution of the high quality imaging
      techniques, vascular lesions in the cauda equina are being diagnosed more
      frequently than ever before. Albeit the demand for accurate knowledge of the
      vascular anatomy in this region, descriptions are often fragmented and not easily
      accessible. In this review, the author attempted to organize the existing
      knowledge of the vascular anatomy in the cauda equina and its implication on the
      vascular lesions in this region. Also reviewed is the clinically relevant
      embryological development of the cauda equina. 

PMID- 27021640
TI  - IRE1alpha mediates PKR activation in response to Chlamydia trachomatis infection.
AB  - Protein kinase RNA activated (PKR) is a crucial mediator of anti-viral responses
      but is reported to be activated by multiple non-viral stimuli. However,
      mechanisms underlying PKR activation, particularly in response to bacterial
      infection, remain poorly understood. We have investigated mechanisms of PKR
      activation in human primary monocyte-derived dendritic cells in response to
      infection by Chlamydia trachomatis. Infection resulted in potent activation of
      PKR that was dependent on TLR4 and MyD88 signalling. NADPH oxidase was
      dispensable for activation of PKR as cells from chronic granulomatous disease
      (CGD) patients, or mice that lack NADPH oxidase activity, had equivalent or
      elevated PKR activation. Significantly, stimulation of cells with endoplasmic
      reticulum (ER) stress-inducing agents resulted in potent activation of PKR that
      was blocked by an inhibitor of IRE1alpha RNAse activity. Crucially, infection
      resulted in robust IRE1alpha RNAse activity that was dependent on TLR4 signalling
      and inhibition of IRE1alpha RNAse activity prevented PKR activation. Finally, we
      demonstrate that TLR4/IRE1alpha mediated PKR activation is required for the
      enhancement of interferon-beta production following C. trachomatis infection.
      Thus, we provide evidence of a novel mechanism of PKR activation requiring ER
      stress signalling that occurs as a consequence of TLR4 stimulation during
      bacterial infection and contributes to inflammatory responses.

PMID- 27021642
TI  - Indication for Partial Vertebral Osteotomy and Realignment in Posterior Spinal
      Fixation for Osteoporotic Thoracolumbar Vertebral Collapse with Neurological
      Deficits.
AB  - Instrumented spinal fixation is ordinarily required in patients who present with
      myelopathy or cauda equina syndrome secondary to vertebral collapse following
      osteoporotic thoracolumbar fracture. Posterior spinal fixation is a major
      surgical option, and partial vertebral osteotomy (PVO) through a posterior
      approach is occasionally reasonable for achievement of complete neural
      decompression and improvement of excessive local kyphosis. However, the
      indications and need for PVO remain unclear. The objectives of this retrospective
      study were to determine the efficacy and safety of posterior spinal fixation with
      or without PVO for osteoporotic thoracolumbar vertebral collapse and identify
      patients who require neural decompression and alignment correction by PVO. We
      retrospectively reviewed the clinical records of 20 patients (13 females, 7
      males; mean age, 67.1 years) who underwent instrumented posterior fixation for
      osteoporotic thoracolumbar vertebral fracture. Clinical outcomes were assessed by
      the Japanese Orthopedic Association score and visual analog scale scores in the
      lumbar and leg areas. PVO was added with posterior spinal fixation in eight
      patients because neural decompression was incomplete after laminectomy as
      indicated by intraoperative echo imaging. Neurological and functional recovery
      significantly improved during follow-up. Clinical outcomes in patients who
      underwent PVO were similar to those in patients who did not undergo PVO. However,
      correction of the local kyphotic angle and improvement of spinal canal compromise
      after surgery was significant in patients who underwent PVO. The patients who
      required PVO had a less local kyphotic angle in the supine position and higher
      occupation rate of the fractured fragment in the spinal canal in the preoperative
      examination. 

PMID- 27021643
TI  - The Importance of Recognizing Diffuse Idiopathic Skeletal Hyperostosis for
      Neurosurgeons: A Review.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by calcification
      and ossification of the soft tissues, mainly ligaments and entheses. The spines
      of patients with DISH generally become increasingly rigid and osteoporotic, and
      fractures may occur after even a relatively minor traumatic event such as a
      ground-level fall. Moreover, the prevalence of DISH may be rapidly increasing in
      affluent societies. Thus, awareness of this condition is becoming more important
      for neurosurgeons when assessing trauma patients. For the present article, a
      literature review was conducted to summarize the current clinical, pathogenetic,
      and therapeutic knowledge of this disease. Furthermore, current treatment
      strategies for DISH-related spine injuries are also reviewed. Although the
      recommended treatment for spinal injuries in DISH patients is surgical, mainly
      through long-segment posterior fusion, rather than conservative options, stable
      fractures without any associated neurologic deficits have often been successfully
      managed with immobilization alone. Percutaneous instrumentation and the use of
      teriparatide may be useful depending on the surgical risks and patient
      neurological status. 

PMID- 27021644
TI  - Fluid phase recognition molecules in neutrophil-dependent immune responses.
AB  - The innate immune system comprises both a cellular and a humoral arm. Neutrophils
      are key effector cells of the immune and inflammatory responses and have emerged
      as a major source of humoral pattern recognition molecules (PRMs). These
      molecules, which include collectins, ficolins, and pentraxins, are specialised in
      the discrimination of self versus non-self and modified-self and share basic
      multifunctional properties including recognition and opsonisation of pathogens
      and apoptotic cells, activation and regulation of the complement cascade and
      tuning of inflammation. Neutrophils act as a reservoir of ready-made soluble
      PRMs, such as the long pentraxin PTX3, the peptidoglycan recognition protein PGRP
      S, properdin and M-ficolin, which are stored in neutrophil granules and are
      involved in neutrophil effector functions. In addition, other soluble PRMs, such
      as members of the collectin family, are not expressed in neutrophils but can
      modulate neutrophil-dependent immune responses. Therefore, soluble PRMs are an
      essential part of the innate immune response and retain antibody-like effector
      functions. Here, we will review the expression and general function of soluble
      PRMs, focusing our attention on molecules involved in neutrophil effector
      functions.

PMID- 27021648
TI  - Dissociable electrophysiological subprocesses during response inhibition are
      differentially modulated by dopamine D1 and D2 receptors.
AB  - Action control is achieved through a multitude of cognitive processes. One of
      them is the ability to inhibit responses, for which the dopaminergic systems is
      known to play an important role. Many lines of psychophysiological research
      substantiate that two distinct response inhibition subprocesses exist, but it has
      remained elusive whether they can be attributed to distinct neurobiological
      factors governing the dopaminergic system. We, therefore, investigated this
      question by examining the effects of DRD1 (rs4532) and DRD2 (rs6277) receptor
      polymorphisms on electrophysiological correlates of response inhibition
      subprocesses (i.e., Nogo-N2 and Nogo-P3) in 195 healthy human subjects with a
      standard Go/Nogo task. The results show that response inhibition performance at a
      behavioral level is affected by DRD1 and DRD2 receptor variation. However, from
      an electrophysiological point of view these effects emerge via different
      mechanisms selectively affected by DRD1 and DRD2 receptor variation. While the D1
      receptor system is associated with pre-motor inhibition electrophysiological
      correlates of response inhibition processes (Nogo-N2), the D2 receptor system is
      associated with electrophysiological correlates of outcome evaluation processes.
      Dissociable cognitive-neurophysiological subprocesses of response inhibition are
      hence attributable to distinct dopamine receptor systems.

PMID- 27021646
TI  - Early hematopoiesis and macrophage development.
AB  - The paradigm that all blood cells are derived from hematopoietic stem cells
      (HSCs) has been challenged by two findings. First, there are tissue-resident
      hematopoietic cells, including subsets of macrophages that are not replenished by
      adult HSCs, but instead are maintained by self-renewal of fetal-derived cells.
      Second, during embryogenesis, there is a conserved program of HSC-independent
      hematopoiesis that precedes HSC function and is required for embryonic survival.
      The presence of waves of HSC-independent hematopoiesis as well as fetal HSCs
      raises questions about the origin of fetal-derived adult tissue-resident
      macrophages. In the murine embryo, historical examination of embryonic macrophage
      and monocyte populations combined with recent reports utilizing genetic lineage
      tracing approaches has led to a model of macrophage ontogeny that can be
      integrated with existing models of hematopoietic ontogeny. The first wave of
      hematopoiesis contains primitive erythroid, megakaryocyte and macrophage
      progenitors that arise in the yolk sac, and these macrophage progenitors are the
      source of early macrophages throughout the embryo, including the liver. A second
      wave of multipotential erythro-myeloid progenitors (EMPs) also arises in the yolk
      sac. EMPs colonize the fetal liver, initiating myelopoiesis and forming
      macrophages. Lineage tracing indicates that this second wave of macrophages are
      distributed in most fetal tissues, although not appreciably in the brain. Thus,
      fetal-derived adult tissue-resident macrophages, other than microglia, appear to
      predominately derive from EMPs. While HSCs emerge at midgestation and colonize
      the fetal liver, the relative contribution of fetal HSCs to tissue macrophages at
      later stages of development is unclear. The inclusion of macrophage potential in
      multiple waves of hematopoiesis is consistent with reports of their functional
      roles throughout development in innate immunity, phagocytosis, and tissue
      morphogenesis and remodeling. Understanding the influences of developmental
      origin, as well as local tissue-specific signals, will be necessary to fully
      decode the diverse functions and responses of tissue-resident macrophages.

PMID- 27021645
TI  - Monocyte-mediated defense against bacteria, fungi, and parasites.
AB  - Circulating blood monocytes are a heterogeneous leukocyte population that
      contributes critical antimicrobial and regulatory functions during systemic and
      tissue-specific infections. These include patrolling vascular tissue for evidence
      of microbial invasion, infiltrating peripheral tissues and directly killing
      microbial invaders, conditioning the inflammatory milieu at sites of microbial
      tissue invasion, and orchestrating the activation of innate and adaptive immune
      effector cells. The central focus of this review is the in vivo mechanisms by
      which monocytes and their derivative cells promote microbial clearance and immune
      regulation. We include an overview of murine models to examine monocyte functions
      during microbial challenges and review our understanding of the functional roles
      of monocytes and their derivative cells in host defense against bacteria, fungi,
      and parasites.

PMID- 27021649
TI  - Interplay between flow and diffusion in capillary alginate hydrogels.
AB  - Alginate gels with naturally occurring macroscopic capillaries have been used as
      a model system to study the interplay between laminar flow and diffusion of
      nanometer-sized solutes in real time. Calcium alginate gels that contain
      homogeneously distributed parallel-aligned capillary structures were formed by
      external addition of crosslinking ions to an alginate sol. The effects of
      different flow rates (0, 1, 10, 50 and 100 MUl min(-1)) and three different
      probes (fluorescein, 10 kDa and 500 kDa fluorescein isothiocyanate-dextran) on
      the diffusion rates of the solutes across the capillary wall and in the bulk gel
      in between the capillaries were investigated using confocal laser scanning
      microscopy. The flow in the capillaries was produced using a syringe pump that
      was connected to the capillaries via a tube. Transmission electron microscopy
      revealed an open aggregated structure close to the capillary wall, followed by an
      aligned network layer and the isotropic network of the bulk gel. The most
      pronounced effect was observed for the 1 nm-diameter fluorescein probe, for which
      an increase in flow rate increased the mobility of the probe in the gel.
      Fluorescence recovery after photobleaching confirmed increased mobility close to
      the channel, with increasing flow rate. Mobility maps derived using raster image
      correlation spectroscopy showed that the layer with the lowest mobility
      corresponded to the anisotropic layer of ordered network chains. The combination
      of microscopy techniques used in the present study elucidates the flow and
      diffusion behaviors visually, qualitatively and quantitatively, and represents a
      promising tool for future studies of mass transport in non-equilibrium systems.

PMID- 27021650
TI  - Corrigendum: CCR7-dependent trafficking of RORgamma(+) ILCs creates a unique
      microenvironment within mucosal draining lymph nodes.

PMID- 27021651
TI  - Knowledge, Perception, and Capacity Regarding Emergency Risk Communication: A
      Cross-Sectional Survey of 429 County Health Emergency Response Staff in
      Chongqing, China.

PMID- 27021652
TI  - Radiodermatitis: A Review of Our Current Understanding.
AB  - Radiodermatitis (radiation dermatitis, radiation-induced skin reactions, or
      radiation injury) is a significant side effect of ionizing radiation delivered to
      the skin during cancer treatment as well as a result of nuclear attacks and
      disasters, such as that which occurred in Fukushima in 2011. More specifically,
      95 % of cancer patients receiving radiation therapy will develop some form of
      radiodermatitis, including erythema, dry desquamation, and moist desquamation.
      These radiation skin reactions result in a myriad of complications, including
      delays in treatment, diminished aesthetic appeal, and reduced quality of life.
      Recent technological advancements and novel treatment regimens have only been
      successful in partly ameliorating these adverse side effects. This article
      examines the current knowledge surrounding the pathogenesis, clinical
      manifestations, differential diagnoses, prevention, and management of
      radiodermatitis. Future research should examine therapies that incorporate the
      current understanding of the pathophysiology of radiodermatitis while measuring
      effectiveness using objective and universal outcome measures. 

PMID- 27021653
TI  - Collective dynamics of diffusiophoretic motors on a filament.
AB  - A variety of uses has been proposed for synthetic chemically powered nanomotors
      that exploit their autonomous directed motion. The collective dynamics of these
      and other active particles display features that differ from their equilibrium
      analogs. We investigate the collective dynamics of chemically powered
      diffusiophoretic motors attached to a filament. Rotational Brownian motion is
      reduced substantially when a motor is attached to a filament and this improves
      motor performance. When many motors are attached to the filament, structural and
      dynamical correlations that may extend over long distances arise. While some
      features of these correlations are due to packing on the filament, there are
      nonequilibrium effects that are due to the local concentration gradients of
      reactive species produced by all motors. As the motor density on the filament
      increases beyond a critical value, the average motor velocity projected along
      motor internuclear axis switches from forward to backward directions. Knowledge
      of the collective dynamics of motors on filaments should prove useful when
      designing ensembles of synthetic motors to perform tasks such as cargo transport
      involving delivery of material to specific regions in complex media. 

PMID- 27021654
TI  - Driven binary colloidal mixture in a 2D narrow channel with hard walls.
AB  - We have investigated the properties of a driven equi-molar binary colloidal
      mixture confined to a two-dimensional narrow channel. The walls are hard and
      periodic boundary condition is applied along the channel. Colloidal particles
      perform Brownian motion in a solvent having a fixed temperature and interact with
      each other via a Debye-Huckel Coulombic interaction (Yukawa potential). A
      constant external force drives the colloids along the channel. Two species move
      oppositely to each other. Hydrodynamic interactions are neglected and the
      dynamics is assumed to be over-damped. The flow increases nonlinearly with the
      external force but does not exhibit a notable dependence on channel width. Above
      a critical driving force the system undergoes a homogeneous-to-laning transition.
      It is shown that the mean lane width as well as the laning order parameter
      increases with the channel width. The reentrance effect is observed in the narrow
      channel geometry. 

PMID- 27021655
TI  - Light-induced Soret effect and adsorption of nanocrystals in organic solvents.
AB  - A light-induced Soret effect accompanied by photoinduced adsorption of pigment
      nanoparticles is described in organic solvents. We report an unexpected inversion
      of the nanoparticle flux which is directed along the temperarture gradient at
      short exposures to the light and switches against the gradient at longer
      exposures. This change of flux direction is due to light-induced adsorption of
      the nanocrystals onto the substrates of the cell. 

PMID- 27021656
TI  - Monogalactosyldiacylglycerol and digalactosyldiacylglycerol role, physical
      states, applications and biomimetic monolayer films.
AB  - The relevance of biomimetic membranes using galactolipids has not been expressed
      in any extensive experimental study of these lipids. Thus, on the one hand, we
      present an in-depth article about the presence and role of
      monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) in
      thylakoid membranes, their physical states and their applications. On the other
      hand, we use the Langmuir and Langmuir-Blodgett (LB) techniques to prepare
      biomimetic monolayers of saturated galactolipids MGDG, DGDG and MGDG:DGDG 2:1
      mixture (MD)--biological ratio--. These monolayers are studied using surface
      pressure-area isotherms and their data are processed to enlighten their physical
      states and mixing behaviour. These monolayers, once transferred to a solid
      substrate at several surface pressures are topographically studied on mica using
      atomic force microscopy (AFM) and using cyclic voltammetry for studying the
      electrochemical behaviour of the monolayers once transferred to indium-tin oxide
      (ITO), which has good optical and electrical properties. Moreover, MD presents
      other differences in comparison with its pure components that are explained by
      the presence of different kinds of galactosyl headgroups that restrict the
      optimal orientation of the MGDG headgroups. 

PMID- 27021657
TI  - Characteristic length scales of the secondary relaxations in glass-forming
      glycerol.
AB  - We investigate the secondary relaxations and their link to the main structural
      relaxation in glass-forming liquids using glycerol as a model system. We analyze
      the incoherent neutron scattering signal dependence on the scattering momentum
      transfer, Q , in order to obtain the characteristic length scale for different
      secondary relaxations. Such a capability of neutron scattering makes it somewhat
      unique and highly complementary to the traditional techniques of glass physics,
      such as light scattering and broadband dielectric spectroscopy, which provide
      information on the time scale, but not the length scales, of relaxation
      processes. The choice of suitable neutron scattering techniques depends on the
      time scale of the relaxation of interest. We use neutron backscattering to
      identify the characteristic length scale of 0.7 A for the faster secondary
      relaxation described in the framework of the mode-coupling theory (MCT). Neutron
      spin-echo is employed to probe the slower secondary relaxation of the excess wing
      type at a low temperature ( ~ 1.13T g . The characteristic length scale for this
      excess wing dynamics is approximately 4.7 A. Besides the Q -dependence, the
      direct coupling of neutron scattering signal to density fluctuation makes this
      technique indispensable for measuring the length scale of the microscopic
      relaxation dynamics. 

PMID- 27021658
TI  - Novel insights into cutaneous immune systems revealed by in vivo imaging.
AB  - In vivo imaging is a novel experimental approach for biological research.
      Multiphoton microscopy (MPM), a type of fluorescence microscopy, is a new tool
      for in vivo imaging analysis. MPM allows observation of both tissue structures
      and cell behaviors or cell-cell interactions in living animals in real time. Skin
      is an ideal tissue for MPM analysis as it is directly accessible to the
      microscope. In the skin, immune cells cooperate to maintain skin homeostasis or
      to exert immune responses against foreign antigens. In vivo imaging by MPM
      analysis provides precise information on cell dynamics in the skin, and has
      significantly expanded our knowledge of the cutaneous immune system. In this
      review, we will discuss recent insights related to the mechanisms of allergic
      skin inflammation that have been revealed by MPM analysis. 

PMID- 27021659
TI  - Intermittent hypoxia upregulates hepatic heme oxygenase-1 and ferritin-1, thereby
      limiting hepatic pathogenesis in rats fed a high-fat diet.
AB  - Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with sleep
      apnea syndrome (SAS). Intermittent hypoxia (IH) and a high-fat diet (HFD)
      reproduce SAS and NAFLD, respectively, in rodents. In this study, rats were fed
      either an HFD or a standard diet (SD) for 2 weeks, and breathed either IH air or
      normoxic air for 4 days (early phase) or 6 weeks (late phase), with the same
      diets maintained during the exposure. HFD increased hepatic lipid accumulation,
      as detected by oil-red staining and triglyceride content. However, IH exposure
      reversed the hepatic steatosis at the late phase in these HFD-rats. IH exposure
      also increased hepatic expression of HO-1 and iron-binding protein ferritin-1 at
      the late phase, in association with increase in serum iron, bilirubin, and
      hepatic levels of lipid peroxides, such as 4-hydroxy-2-nonenal (HNE). IH exposure
      increased serum levels of hemoglobin (Hb) at the early phase and
      immunofluorescence of Hb and HO-1 in CD68-positive Kupffer cells (KCs) at the
      late phase. These findings support that IH induces erythrocytosis, erythro
      phagocytosis, and generation of Hb in the KCs. The Hb promotes HO-1 expression in
      KCs, thereby produces iron, bilirubin, and carbon monoxide (CO). The iron would
      be either sequestrated by ferritin-1, transferred to the bone marrow for
      erythropoiesis, or would produce hydroxyradicals and HNE in the liver of rats fed
      an HFD. HNE might also contribute to the upregulation of HO-1, transferrin-1, and
      IkappaB, thereby limiting hepatic steatosis and inflammation via inhibition of
      nuclear factor kappaB (NFkappaB) activation. 

PMID- 27021660
TI  - Evaluation of Ag containing hydroxyapatite coatings to the Candida albicans
      infection.
AB  - In this research work, the synthesis of Ag doped hydroxyapatite coatings for
      dental or orthopedic implants was performed. The main goal was to determine the
      influence of Ag content on the roughness and antimicrobial performance of the
      prepared thin films. The films were deposited on Ti6Al4V alloy by means of RF
      magnetron sputtering. Those coatings were characterized by X-ray diffraction
      (XRD) and 3D surface profilometry. The antifungal activity after 1 and 7days of
      culture was evaluated in the presence of Candida albicans (ATCC - 10231). The
      increase of Ag content increased roughness and reduced the antifungal activity.
      The results showed that the Ag doped hydroxyapatite coatings can be a potential
      solution for the improvement of the antifungal activities of Ti based alloy. 

PMID- 27021661
TI  - Optimisation of a droplet digital PCR assay for the diagnosis of Schistosoma
      japonicum infection: A duplex approach with DNA binding dye chemistry.
AB  - Schistosomiasis is a chronically debilitating helminth infection with a
      significant socio-economic and public health impact. Accurate diagnostics play a
      pivotal role in achieving current schistosomiasis control and elimination goals.
      However, many of the current diagnostic procedures, which rely on detection of
      schistosome eggs, have major limitations including lack of accuracy and the
      inability to detect pre-patent infections. DNA-based detection methods provide a
      viable alternative to the current tests commonly used for schistosomiasis
      diagnosis. Here we describe the optimisation of a novel droplet digital PCR
      (ddPCR) duplex assay for the diagnosis of Schistosoma japonicum infection which
      provides improved detection sensitivity and specificity. The assay involves the
      amplification of two specific and abundant target gene sequences in S. japonicum;
      a retrotransposon (SjR2) and a portion of a mitochondrial gene (nad1). The assay
      detected target sequences in different sources of schistosome DNA isolated from
      adult worms, schistosomules and eggs, and exhibits a high level of specificity,
      thereby representing an ideal tool for the detection of low levels of parasite
      DNA in different clinical samples including parasite cell free DNA in the host
      circulation and other bodily fluids. Moreover, being quantitative, the assay can
      be used to determine parasite infection intensity and, could provide an important
      tool for the detection of low intensity infections in low prevalence
      schistosomiasis-endemic areas.

PMID- 27021662
TI  - Multiplex real-time PCR assay for the detection of extended-spectrum beta
      lactamase and carbapenemase genes using melting curve analysis.
AB  - Real-time PCR melt curve assays for the detection of beta-lactamase, extended
      spectrum beta-lactamase and carbapenemase genes in Gram-negative bacteria were
      developed. Two multiplex real-time PCR melt curve assays were developed for the
      detection of ten common beta-lactamase genes: blaKPC-like, blaOXA-48-like, blaNDM
      like, blaVIM-like, blaIMP-like, blaCTX-M-1+2-group, blaCMY-like, blaACC-like,
      blaSHV-like and blaTEM-like. The assays were evaluated using 25 bacterial strains
      and 31 DNA samples (total n=56) comprising different Enterobacteriaceae genera
      and Pseudomonas spp. These strains were previously characterized at five research
      institutes. Each resistance gene targeted in this study generated a non
      overlapping and distinct melt curve peak. The assay worked effectively and
      detected the presence of additional resistance genes in 23 samples. The assays
      developed in this study offer a simple, low cost method for the detection of
      prevalent beta-lactamase, ESBL and carbapenemase genes among Gram-negative
      pathogens. 

PMID- 27021663
TI  - Development of simple sequence repeat (SSR) markers for discrimination among
      isolates of Fusarium proliferatum.
AB  - The plant pathogen Fusarium proliferatum has a wide host range and occurs
      worldwide. Many isolates of the fungus produce mycotoxins in plant tissues,
      which, if ingested, can cause harm to animals and humans. In 2008, an outbreak of
      salmon blotch of onions, caused by F. proliferatum, was detected in southern
      Israel. The source and distribution of the fungus in Israel were unknown. Inter
      simple sequence repeats (ISSR) were used to identify repetitive motifs present in
      seven isolates of F. proliferatum from Israel, Germany and Austria. ISSR repeat
      motifs were, used to develop 17 simple sequence repeat (SSR) loci. Six of these
      SSR markers were polymorphic in and consistently amplified from ten isolates
      collected in Israel, Germany, Austria and North America, from cucumber, onion,
      garlic, maize, and asparagus. These six polymorphic SSR alleles included 5 to 12
      copies of di-, tri, and pentanucleotide motifs and yielded six to 9 alleles each.
      Sixteen of the SSR loci were amplified at least one of the seven Fusarium
      species, F. verticillioides, F. thapsinum, F. subglutinans, F. andiyazi, F.
      globosum, F. fujikoroi and F. oxysporum. The data demonstrate that these SSRs can
      be used for characterization of F. proliferatum isolates from diverse hosts and
      geographic locations and that they are transferable to other species of Fusarium.

PMID- 27021664
TI  - Case Review: 17-Year-Old-Female With Respiratory Depression as a Result of Opioid
      Overdose.

PMID- 27021666
TI  - A 56-Year-Old Man With an Asthma Exacerbation.

PMID- 27021667
TI  - Acute Respiratory Distress Syndrome and Lung Protection.

PMID- 27021669
TI  - Articles That May Change Your Practice: Crew Resource Management.

PMID- 27021668
TI  - A Horse Is a Horse, of Course, of Course.

PMID- 27021671
TI  - Interprofessional Flight Camp.
AB  - The Dorothy Ebersbach Academic Center for Flight Nursing in Cleveland, OH, holds
      an annual flight camp designed for master's degree nursing students in the acute
      care nurse practitioner program, subspecializing in flight nursing at the Frances
      Payne Bolton School of Nursing at Case Western Reserve University. The weeklong
      interprofessional training is also open to any health care provider working in an
      acute care setting and focuses on critical care updates, trauma, and emergency
      care within the critical care transport environment. This year, 29 graduate
      nursing students enrolled in a master's degree program from Puerto Rico attended.
      Although the emergency department in Puerto Rico sees and cares for trauma
      patients, there is no formal trauma training program. Furthermore, the country
      only has 1 rotor wing air medical transport service located at the Puerto Rico
      Medical Center in San Juan. Flight faculty and graduate teaching assistants spent
      approximately 9 months planning for their participation in our 13th annual flight
      camp. Students from Puerto Rico were extremely pleased with the learning
      experiences at camp and expressed particular interest in having more training
      time within the helicopter flight simulator. 

PMID- 27021672
TI  - Pediatric Specialty Transport Teams Are Not Associated With Decreased 48-Hour
      Pediatric Intensive Care Unit Mortality: A Propensity Analysis of the VPS, LLC
      Database.
AB  - OBJECTIVE: The purpose of this study was to determine if pediatric specialty
      pediatric team (SPT) interfacility-transported children from community emergency
      departments to a pediatric intensive care unit (PICU) have improved 48-hour
      mortality. METHODS: This is a multicenter, historic cohort analysis of the VPS,
      LLC PICU clinical database (VPS, LLC, Los Angeles, CA) for all PICU directly
      admitted pediatric patients <= 18 years of age from January 1, 2007, to March 31,
      2009. Categoric variables were analyzed by the chi-square and Mann-Whitney tests
      for non-normally distributed continuous variables. The propensity score was
      determined by multiple logistic regression analysis. Nearest neighbor matching
      developed emergency medical services SPT pairs by similar propensity score.
      Multiple regression analyses of the matched pairs determined the association of
      SPT with 48-hour PICU mortality. P values < .05 were considered significant.
      RESULTS: This study included 3,795 PICU discharges from 12 hospitals. SPT
      transported children were more severely ill, younger in age, and more likely to
      have a respiratory diagnosis (P < .0001). Unadjusted 48-hour PICU mortality was
      statistically significantly higher for SPT transports (2.04% vs. 0.070%, P =
      .0028). Multiple regressions adjusted for propensity score, illness severity, and
      PICU site showed no significant difference in 48-hour PICU mortality. CONCLUSION:
      No significant difference in adjusted 48-hour PICU mortality for children
      transported by transport team type was discovered.

PMID- 27021673
TI  - LUCAS(TM)2 in Danish Search and Rescue Helicopters.
AB  - OBJECTIVE: Prehospital resuscitation is often challenging. Giving uninterrupted
      and effective compressions is relatively impossible during transportation. In
      2012, The Royal Danish Air Force received a donation of 8 mechanical chest
      compression devices (LUCAS(TM)2; Physio-Control/Jolife AB, Lund, Sweden) to be
      used onboard the Danish search and rescue (SAR) helicopters. The scope of this
      investigation was to establish whether or not mechanical chest compression
      devices should be considered a necessity onboard the Danish SAR helicopters.
      METHODS: Data were compiled from SAR medical journals. From the data collected,
      observations were made as to when LUCAS(TM)2 was used and what diagnosis the SAR
      physician made. RESULTS: One thousand ninety missions were registered in the 24
      month research period, and LUCAS(TM)2 was used in 25 missions. Cardiac
      emergencies amounted for 25% of the missions. CONCLUSION: The Danish SAR
      helicopters retrieved 33 drowned/hypothermic patients during the research period,
      and the LUCAS(TM)2 was used in 11 of the patients requiring resuscitation. The
      LUCAS(TM)2 was frequently used during other emergencies like sudden cardiac
      arrest. Cardiac emergencies were the predominant type of mission. LUCAS(TM)2 is
      now considered mandatory on Danish SAR helicopters.

PMID- 27021674
TI  - High-Dose Ketamine Sedation of an Agitated Patient During Air Medical Transport.
AB  - We report a case in which a high-dose ketamine infusion was used to sedate an
      agitated patient for air medical transport, avoiding the risks of general
      anesthesia and causing no exacerbation of psychiatric symptoms.

PMID- 27021675
TI  - Resuscitation of a Pediatric Drowning in Hypothermic Cardiac Arrest.
AB  - The prognosis of pediatric patients who require prolonged resuscitation after ice
      water drowning and hypothermic cardiac arrest remains guarded. We report a case
      of successful prolonged resuscitation of a pediatric patient in hypothermic
      cardiac arrest who showed severe metabolic derangements and went on to make a
      rapid and full neurologic recovery without the use of extracoproreal rewarming or
      mechanical cardiac support. Many ground and air medical emergency medical service
      programs have policies against interfacility transfer of patients in hypothermic
      cardiac arrest, calling into question the need to revise current protocols. 

PMID- 27021676
TI  - A Challenging Penetrating Trauma Case.
AB  - We present the prehospital management of a 23-year-old Australian Aboriginal man
      with an isolated knife stab wound to the posterior right chest. The lead author
      attended to the prehospital management of this young man during tenure as a
      registrar in retrieval medicine for CareFlight Medical Services (CMS) in North
      Queensland, Australia. The case is noteworthy because it involved a combination
      of a life-threatening injury with a superimposed iatrogenic injury. The case will
      be of interest to physicians and clinicians in prehospital medicine as well as
      those in low-volume emergency departments or facilities in which major trauma may
      present infrequently. 

PMID- 27021679
TI  - A novel selective inhibitor to thrombin-induced platelet aggregation purified
      from the leech Whitmania pigra.
AB  - BACKGROUND/AIM: The dried whole body of the leech Whitmania pigra, a well-known
      traditional Chinese medicine, has been widely used to treat thrombus diseases for
      thousands of years. However, its bioactive constituents were reported rarely. The
      aim of our study was to investigate antithrombotic components of it. METHODS: The
      antithrombotic peptide was purified using a combination of anion-exchange
      chromatography, ultrafiltration and reverse-phase HPLC. the sequence of the
      peptide was determined using MALDI-TOF-MS-MS. Anti-platelet aggregation activity
      in vitro was evaluated using a turbidimetric method, and antithrombotic effect in
      vivo was assessed in an arterio-venous shunt thrombosis model in rats. RESULTS: A
      novel antithrombotic peptide named WP-30, with the sequence
      VISRTQSNVQAAWGQVGGHAADYSAVAIER, was isolated from the dried whole body of the
      leech W. pigra. WP-30 selectively inhibited thrombin-induced anti-platelet
      aggregation in vitro, and potently attenuated thrombus formation in rats in vivo.
      CONCLUSIONS: Taken together, we found a novel peptide from leech bodies, and this
      peptide showed antiplatelet aggregation and antithrombotic effects.

PMID- 27021680
TI  - High-fat diet-induced obesity stimulates ketone body utilization in osteoclasts
      of the mouse bone.
AB  - Previous studies have shown that high-fat diet (HFD)-induced obesity increases
      the acetoacetyl-CoA synthetase (AACS) gene expression in lipogenic tissue. To
      investigate the effect of obesity on the AACS gene in other tissues, we examined
      the alteration of AACS mRNA levels in HFD-fed mice. In situ hybridization
      revealed that AACS was observed in several regions of the embryo, including the
      backbone region (especially in the somite), and in the epiphysis of the adult
      femur. AACS mRNA expression in the adult femur was higher in HFD-fed mice than in
      normal-diet fed mice, but this increase was not observed in high sucrose diet
      (HSD)-induced obese mice. In addition, HFD-specific increases were observed in
      the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and interleukin (IL)
      6 genes. Moreover, we detected higher AACS mRNA expression in the differentiated
      osteoclast cells (RAW 264), and found that AACS mRNA expression was significantly
      up-regulated by IL-6 treatment only in osteoclasts. These results indicate the
      novel function of the ketone body in bone metabolism. Because the abnormal
      activation of osteoclasts by IL-6 induces bone resorption, our data suggest that
      AACS and ketone bodies are important factors in the relationship between obesity
      and osteoporosis. 

PMID- 27021681
TI  - Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis
      during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2
      and P38 signaling pathways.
AB  - Ischemic heart disease is one of the most common diseases in modern society.
      Ischemic myocardium can be salvaged by vascular recanalization therapy, but its
      benefit is attenuated by injury that can occur during reperfusion. And apoptotic
      cell death plays an important part in myocardial ischemia-reperfusion (IR)
      injury. Regulator of G-protein signaling 5 (RGS5), highly expressed in different
      cell types of the human adult heart, is a guanosine triphosphatase-activating
      protein to inhibit many signaling pathways such as c-Jun NH2-terminal kinase 1/2
      (JNK1/2) and p38 which promote cardiac IR-induced apoptosis. However the role of
      RGS5 in cardiac IR-induced apoptosis remains unclear. An in vitro IR model was
      applied to the isolated hearts of wild type mice (WT), RGS5-transgenic mice (TG),
      and RGS5-knockout mice (KO). Our results revealed that compared with either WT or
      KO mice, TG mice showed inhibition of cardiomyocyte apoptosis as indicated by a
      greater increase of B cell lymphoma/lewkmia-2 (Bcl-2), and an obvious reduction
      in the positive expression of the terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL), Bcl-2 Associated X protein (Bax), and active
      caspase-3. Moreover, the inhibition of both JNK1/2 and p38 signaling markedly
      reversed IR-induced cardiomyocyte apoptosis in RGS5-KO mice. These studies show
      that RGS5 protects cardiomyocytes against apoptosis during IR through inhibiting
      both JNK1/2 and p38 signaling pathways. 

PMID- 27021682
TI  - Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by
      inhibiting TGF-beta1.
AB  - Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young
      adolescents. This study explored the function of halofuginone (HF) in
      Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited
      higher survival rate, lower heart/body weight, and more decreased blood sugar
      concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)
      17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro
      inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The
      expressions of transforming growth factor(TGF-beta1) and nuclear factor kappa
      light-chain-enhancer of activated B (NF-kappaB) p65/ tumor necrosis factor-alpha
      (TNF-alpha) proteins were decreased by HF as well. Finally, the overexpression of
      TGF-beta1 counteracted the protection effect of HF in CVB3-treated suckling mice.
      In summary, our study suggests HF increases the survival of CVB3 suckling mice,
      reduces the Th17 cells and pro-inflammatory cytokine levels, and may through
      downregulation of the TGF-beta1-mediated expression of NF-kappaB p65/TNF-alpha
      pathway proteins. These results offer a potential therapeutic strategy for the
      treatment of VMC. 

PMID- 27021683
TI  - MiR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell
      proliferation, apoptosis and differentiation by targeting Dnmt1 and promoting
      SOD2 expression.
AB  - miR-140-5p is down-regulated in patients with pulmonary arterial hypertension
      (PAH) and experimental models of PAH, and inhibits hypoxia-mediated pulmonary
      artery smooth muscle cell (PASMC) proliferation in vitro. Delivery of synthetic
      miR-140-5p prevents and treats established, experimental PAH. DNA
      methyltransferase 1 (Dnmt1) is up-regulated in PAH associated human PASMCs
      (HPASMCs), which promotes the development of PAH by hypermethylation of CpG
      islands within the promoter for superoxide dismutase 2 (SOD2) and down-regulating
      SOD2 expression. We searched for miR-140-5p targets using TargetScan, PicTar and
      MiRanda tools, and found that Dnmt1 is a potential target of miR-140-5p. Based on
      these findings, we speculated that miR-140-5p might target Dnmt1 and regulate
      SOD2 expression to regulate hypoxia-mediated HPASMC proliferation, apoptosis and
      differentiation. We detected the expression of miR-140-5p, Dnmt1 and SOD2 by
      quantitative real-time polymerase chain reaction (qRT-PCR) and western blot
      assays, respectively, and found down-regulation of miR-140-5p and SOD2 and up
      regulation of Dnmt1 exist in PAH tissues and hypoxia-mediated HPASMCs. Cell
      proliferation, apoptosis and differentiation detection showed that miR-140-5p
      inhibits proliferation and promotes apoptosis and differentiation of HPASMCs in
      hypoxia, while the effect of Dnmt1 on hypoxia-mediated HPASMCs is reversed.
      Luciferase assay confirmed that miR-140-5p targets Dnmt1 directly. An inverse
      correlation is also found between miR-140-5p and Dnmt1 in HPASMCs. In addition,
      we further investigated whether miR-140-5p and Dnmt1 regulate HPASMC
      proliferation, apoptosis and differentiation by regulating SOD2 expression, and
      the results confirmed our speculation. Taken together, these results indicated
      that miR-140-5p at least partly targets Dnmt1 and regulates SOD2 expression to
      inhibit proliferation and promote apoptosis and differentiation of HPASMCs in
      hypoxia.

PMID- 27021684
TI  - Screening sourdough samples for gliadin-degrading activity revealed Lactobacillus
      casei strains able to individually metabolize the coeliac-disease-related 33-mer
      peptide.
AB  - A selective culture medium containing acid-hydrolyzed gliadins as the sole
      nitrogen source was used in the search for sourdough-indigenous lactic acid
      bacteria (LAB) with gliadin-metabolizing activity. Twenty gliadin-degrading LAB
      strains were isolated from 10 sourdoughs made in different ways and from
      different geographical regions. Fifteen of the 20 isolated strains were
      identified as Lactobacillus casei, a species usually reported as subdominant in
      sourdough populations. The other 5 gliadin-degrading strains belonged to the more
      commonly encountered sourdough species Leuconostoc mesenteroides and
      Lactobacillus plantarum. All these strains were shown to be safe in terms of
      their resistance to antimicrobial agents. When individually incubated with the
      alpha2-gliadin-derived immunotoxic 33-mer peptide (97.5 ppm), half of the L.
      casei strains metabolized at least 50% of it within 24 h. One strain metabolized
      82% of the 33-mer peptide within 8 h and made it fully disappear within 12 h.
      These results reveal for the first time the presence in sourdough of proteolytic
      L. casei strains with the capacity to individually metabolize the coeliac-disease
      related 33-mer peptide. 

PMID- 27021685
TI  - Affinity-based separations in bioanalysis.

PMID- 27021686
TI  - Magnetic Resonance Imaging-Derived Renal Oxygenation and Perfusion During
      Continuous, Steady-State Angiotensin-II Infusion in Healthy Humans.
AB  - BACKGROUND: The role of kidney hypoxia is considered pivotal in the progression
      of chronic kidney disease. A widely used method to assess kidney oxygenation is
      blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its
      interpretation remains problematic. The BOLD-MRI signal is the result of kidney
      oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular
      perfusion). Therefore, we hypothesized that with pharmacological modulation of
      kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to
      filtration fraction (ie, glomerular filtration rate/effective renal plasma flow)
      in healthy humans. METHODS AND RESULTS: Eight healthy volunteers were subjected
      to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At
      each dose, renal oxygenation and blood flow were assessed using BOLD and phase
      contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective
      renal plasma flow measurements were performed under the same conditions. Renal
      plasma flow decreased dose dependently from 660+/-146 to 467+/-103 mL/min per
      1.73 m(2) (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from
      121+/-23 to 110+/-18 mL/min per 1.73 m(2) (F[1.8, 2.4]=6.4, P=0.013). Cortical
      transverse relaxation rate (R2*; increases in R2* represent decreases in
      oxygenation) increased by 7.2+/-3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did
      not change. Cortical R2* related to filtration fraction (R(2) 0.46, P<0.001).
      CONCLUSIONS: By direct comparison between "gold standard" kidney function
      measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD
      MRI relates poorly to glomerular filtration rate but is associated with
      filtration fraction. For future studies, there may be a need to include renal
      plasma flow measurements when employing renal BOLD-MRI.

PMID- 27021688
TI  - Mexican medicinal plants with anxiolytic or antidepressant activity: Focus on
      preclinical research.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety and depression are considered the most
      prevalent psychiatric disorders worldwide. In Mexico, the use of medicinal plants
      to alleviate the symptoms associated with these psychiatric disorders is
      increasing. However, there is little scientific evidence that validates the
      efficacy of these plants. This evidence needs to be critically revised, and
      further studied to provided scientific support for their use. AIM OF THE STUDY:
      To identify the plants that are used in Mexico for the treatment of disorders
      related to anxiety and depression, and to review the current preclinical and when
      available, clinical information of these plants. METHODS: We searched in
      scientific databases (Pubmed, Web of Science, Scopus and other web sources such
      as "Biblioteca digital de la medicina tradicional Mexicana" ) for Mexican plants
      used for the treatment of anxiety and depression that have been analyzed in
      preclinical studies. Additional information was obtained from published books.
      For this review, we also consider those plants used in Mexican traditional
      medicine for the treatment of "nervios," "susto" or "espanto;" common terms that
      describe symptoms related to anxiety and depression disorders. RESULTS: The
      bibliographic search identified 49 plants used in Mexican traditional medicine
      for the treatment of disorders related to anxiety and depression. From all these
      plants, 59% were analyzed in preclinical research, and only 8% were tested in
      clinical studies; only a few of these studies tried to elucidate their mechanism
      of action. In general, it is proposed that the plant extracts interact with the
      GABAergic system. However, only part of these studies attempted to analyze other
      neurotransmitter systems. Finally, in some cases, drug-herbal interactions were
      reported. CONCLUSIONS: There is a large number of Mexican medicinal plants used
      as a treatment for anxiety and depression disorders. Although some of these
      plants have been studied in preclinical research, in most cases these studies are
      preliminary, and the understanding of the mechanism of action is inconclusive.
      The need for systematic studies in preclinical and clinical research is evident,
      and efforts should be done to fulfill these research. Finally, it is important
      also to study possible drug-herbal interactions to establish specific
      recommendations for people that use these plants as anxiolytic or antidepressant
      treatments either alone or in combination with another type of medicine.

PMID- 27021687
TI  - Trojan-Like Internalization of Anatase Titanium Dioxide Nanoparticles by Human
      Osteoblast Cells.
AB  - Dentistry and orthopedics are undergoing a revolution in order to provide more
      reliable, comfortable and long-lasting implants to patients. Titanium (Ti) and
      titanium alloys have been used in dental implants and total hip arthroplasty due
      to their excellent biocompatibility. However, Ti-based implants in human body
      suffer surface degradation (corrosion and wear) resulting in the release of
      metallic ions and solid wear debris (mainly titanium dioxide) leading to peri
      implant inflammatory reactions. Unfortunately, our current understanding of the
      biological interactions with titanium dioxide nanoparticles is still very
      limited. Taking this into consideration, this study focuses on the
      internalization of titanium dioxide nanoparticles on primary bone cells,
      exploring the events occurring at the nano-bio interface. For the first time, we
      report the selective binding of calcium (Ca), phosphorous (P) and proteins from
      cell culture medium to anatase nanoparticles that are extremely important for
      nanoparticle internalization and bone cells survival. In the intricate biological
      environment, anatase nanoparticles form bio-complexes (mixture of proteins and
      ions) which act as a kind of 'Trojan-horse' internalization by cells.
      Furthermore, anatase nanoparticles-induced modifications on cell behavior
      (viability and internalization) could be understand in detail. The results
      presented in this report can inspire new strategies for the use of titanium
      dioxide nanoparticles in several regeneration therapies.

PMID- 27021689
TI  - Psychosocial Constructs as Possible Moderators of Self-Reported Driving
      Restrictions.
AB  - To date, associations between psychosocial driving variables and behaviour have
      been examined only cross-sectionally. Using three waves of data collected
      annually from 928 older drivers (mean age = 76.21 years; 62% male) enrolled in
      the Candrive II cohort, we examined in this study whether changes in attitudes
      and perceptions towards driving (decisional balance and day and night driving
      comfort) were associated with changes in older adults' reported restrictions in
      driving practices and perceived driving abilities. Multi-level models revealed
      that older adults who showed an increase in negative attitudes towards driving
      over time were more likely to report more-restricted practices (greater avoidance
      of challenging driving situations) and perceived declines in driving abilities
      compared to individuals whose attitudes towards driving remained stable across
      two years. This work supports previous findings and offers a new understanding of
      how attitudes relate to driving perceptions (e.g., comfort) and self-regulation
      in older adults over time.

PMID- 27021691
TI  - Potential impact of land use change on ecosystem services in China.
AB  - Land use change can greatly alter spatial pattern and overall ecosystem service
      values (ESV). The goal of this study was to explore the likely effects of land
      use change on ESV in China. In this paper, the spatially explicit land use
      changes across China from 2010 to 2020 under the 2000s trend scenario and the
      planning scenario were projected using the Dyna-CLUE model. The ESV evaluation
      method was improved by adjusting the ESV coefficients using biomass data to
      reduce the generalization error of proxy-based method. The results revealed that
      between 2010 and 2020, total ESV increased by 1798 and 2215 billion RMB a(-1)
      under the 2000s trend scenario and the planning scenario, respectively. The
      spatial pattern of ESV in 2010 and 2020 presented a logical geographic
      distribution. The areas with ESV of 50,000 RMB ha(-1) a(-1) and higher occurred
      primarily in northeastern and southern China, while the areas with ESV of 5000
      RMB ha(-1) a(-1) and lower were mainly located in northwestern China. The spatial
      differences between the two scenarios were insignificant except that the increase
      of ESV in southwestern China was more prominent in the planning scenario than
      that in the 2000s trend scenario, while the total ESV in 2020 under the planning
      scenario was larger than that in the 2000s trend scenario. The increase of ESV
      occurred mainly in northeastern, southern, and southeastern China due to forest
      growth and woodland expansion in 2020 compared with 2010. The results of this
      study can provide useful information for the public and land managers to
      consider. 

PMID- 27021690
TI  - Isolation and identification of nontuberculous mycobacteria from hospitalized
      patients and drinking water samples--examination of their correlation by
      chemometrics.
AB  - Nontuberculous mycobacteria (NTM) have been found to be widely dispersed in the
      environment and are being considered potentially pathogenic for humans and
      animals, while reports of their human to human transmission are absent. Water and
      aerosols are potential transmission modes of NTM to humans. Hospitalized patients
      with NTM infections were studied together with drinking water samples from their
      respective residence areas during 2003-2013. Cluster analysis and factor analysis
      were used to analyze the data matrix. A total of 367 hospitalized patients living
      in 30 localities in the Prefecture of Larissa were tested positive for NTM. The
      most frequently isolated NTM species of the 383 NTM isolates from the clinical
      specimens were Mycobacterium fortuitum (n = 118, 30.8 %), M. gordonae (n = 87,
      22.7 %), M. peregrinum (n = 46, 12.0 %), M. chelonae (n = 11, 2.9 %), M. avium (n
      = 8, 2.1 %), and M. intracellulare (n = 7, 1.8 %), while 88 (23.0 %) of these
      isolates were not identified. It is noted that in 8 patients, M. tuberculosis was
      isolated simultaneously with one NTM, in 15 patients, together with two types of
      NTM, while in 1 patient, it was found at the same time as three different NTM. In
      addition, 3360 drinking water samples were collected from 30 localities and
      analyzed during 2010 to 2013; they were found 11.2 % NTM positive. Cluster
      analysis and factor analysis results confirm that NTM strains are correlated to
      each other in both isolated samples from patients and drinking water, while the
      strength of their correlation varied from weak to moderate (e.g., factor loadings
      ranged from 0.69 to 0.74 when all data are considered). These results provide
      indications that drinking water could be linked with NTM cases in humans. 

PMID- 27021692
TI  - A practitioner's guide for exploring water quality patterns using principal
      components analysis and Procrustes.
AB  - To design sustainable water quality monitoring programs, practitioners must
      choose meaningful variables, justify the temporal and spatial extent of
      measurements, and demonstrate that program objectives are successfully achieved
      after implementation. Consequently, data must be analyzed across several
      variables and often from multiple sites and seasons. Multivariate techniques such
      as ordination are common throughout the water quality literature, but methods
      vary widely and could benefit from greater standardization. We have found little
      clear guidance and open source code for efficiently conducting ordination to
      explore water quality patterns. Practitioners unfamiliar with techniques such as
      principal components analysis (PCA) are faced with a steep learning curve to
      summarize expansive data sets in periodic reports and manuscripts. Here, we
      present a seven-step framework for conducting PCA and associated tests. The last
      step is dedicated to conducting Procrustes analysis, a valuable but rarely used
      test within the water quality field that describes the degree of concordance
      between separate multivariate data matrices and provides residual values for
      similar points across each matrix. We illustrate the utility of these tools using
      three increasingly complex water quality case studies in US parklands. The case
      studies demonstrate how PCA and Procrustes analysis answer common applied
      monitoring questions such as (1) do data from separate monitoring locations
      describe similar water quality regimes, and (2) what time periods exhibit the
      greatest water quality regime variability? We provide data sets and annotated R
      code for recreating case study results and as a base for crafting new code for
      similar monitoring applications. 

PMID- 27021693
TI  - Budgeting of major nutrients and the mitigation options for nutrient mining in
      semi-arid tropical agro-ecosystem of Tamil Nadu, India using NUTMON model.
AB  - Mining of nutrients from soil is a major problem in developing countries causing
      soil degradation and threaten long-term food production. The present study
      attempts to apply NUTrient MONitoring (NUTMON) model for carrying out nutrient
      budgeting to assess the stocks and flows of nitrogen (N), phosphorus (P), and
      potassium (K) in defined geographical unit based on the inputs, viz., mineral
      fertilizers, manures, atmospheric deposition, and sedimentation, and outputs,
      viz., harvested crop produces, residues, leaching, denitrification, and erosion
      losses. The study area covers Coimbatore and Erode Districts, which are potential
      agricultural areas in western agro-ecological zone of Tamil Nadu, India. The
      calculated nutrient balances for both the districts at district scale, using
      NUTMON methodology, were negative for nitrogen (N -3.3 and -10.1 kg ha(-1)) and
      potassium (K -58.6 and -9.8 kg ha(-1)) and positive for phosphorus (P +14.5 and
      20.5 kg ha(-1)). Soil nutrient pool has to adjust the negative balance of N and
      K; there will be an expected mining of nutrient from the soil reserve. A strategy
      was attempted for deriving the fertilizer recommendation using Decision Support
      System for Integrated Fertilizer Recommendation (DSSIFER) to offset the mining in
      selected farms. The results showed that when DSSIFER recommended fertilizers are
      applied to crops, the nutrient balance was positive. NUTMON-Toolbox with DSSIFER
      would serve the purpose on enhancing soil fertility, productivity, and
      sustainability. The management options to mitigate nutrient mining with an
      integrated system approach are also discussed. 

PMID- 27021694
TI  - The occurrence and sources of heavy metal contamination in peri-urban and
      smelting contaminated sites in Baoji, China.
AB  - Atmospheric deposition, soil, plant, ore, and coal cinder samples were collected
      and analyzed to determine heavy metal concentrations in a typical peri-urban
      industrial area of Baoji. The lead isotope ratio method was employed to trace the
      source and dispersion of atmospheric heavy metal contamination. Results showed
      that concentrations of lead, zinc, cadmium, and copper in atmospheric deposition
      significantly exceed soil background levels and Chinese soil environmental
      quality standards. The most polluted sites were located in the downwind direction
      of the smelter, which confirmed this site to be the major pollution source for
      this area. The other source of heavy metals in this area is a power plant. The
      investigation into lead isotopes revealed compositions in atmospheric deposition
      samples were similar to those in ores and coal cinders identifying smelting as
      the predominant pollution source of lead with the power plant having a minimal
      effect. Similar isotopic compositions were also found in plants, indicating that
      the major source of lead in plants was derived from atmospheric deposition,
      although some evidence was found to suggest uptake from the soil to the roots as
      an additional contaminant pathway. 

PMID- 27021695
TI  - Complex electronic waste treatment - An effective process to selectively recover
      copper with solutions containing different ammonium salts.
AB  - Recovery of valuable metals from electronic waste has been highlighted by the EU
      directives. The difficulties for recycling are induced by the high complexity of
      such waste. In this research, copper could be selectively recovered using an
      ammonia-based process, from industrially processed information and communication
      technology (ICT) waste with high complexity. A detailed understanding on the role
      of ammonium salt was focused during both stages of leaching copper into a
      solution and the subsequent step for copper recovery from the solution. By
      comparing the reactivity of the leaching solution with different ammonium salts,
      their physiochemical behaviour as well as the leaching efficiency could be
      identified. The copper recovery rate could reach 95% with ammonium carbonate as
      the leaching salt. In the stage of copper recovery from the solution,
      electrodeposition was introduced without an additional solvent extraction step
      and the electrochemical behaviour of the solution was figured out. With a careful
      control of the electrodeposition conditions, the current efficiency could be
      improved to be 80-90% depending on the ammonia salts and high purity copper
      (99.9wt.%). This research provides basis for improving the recyclability and
      efficiency of copper recovery from such electronic waste and the whole process
      design for copper recycling.

PMID- 27021696
TI  - The composition analysis and preliminary cultivation optimization of a PHA
      producing microbial consortium with xylose as a sole carbon source.
AB  - This work aimed at using xylose as sole substrate, and combining feast-famine
      process with Nile blue staining as well as denaturing gradient gel
      electrophoresis (DGGE) analysis to screen polyhydroxyalkanoate (PHA)-producing
      bacteria from waste activated sludge (WAS). Composition changes of the microbial
      consortium during domestication were analyzed by DGGE, and the results indicated
      that there were mainly four classes of bacteria in the final stable system, which
      were gamma-Proteobacteria, Cellvibrio sp., an uncultured bacterium and
      Pseudomonas sp., respectively. After preliminary optimization, the optimal
      conditions for the microbial consortium to produce PHA were also obtained as
      follows: temperature 33 degrees C, pH 8, xylose concentration 2.4g/L, C/N ratio
      160 and C/P ratio 125. The final PHA accumulation was up to 31% of dry cell
      weight (DCW), compared to 23.8% of the original consortia. Though our process is
      at the very beginning and the PHA yield is relatively low, producing PHA from
      xylose by using microbial consortia is a promising way to save the PHA production
      cost. 

PMID- 27021697
TI  - Generation and detection of metal ions and volatile organic compounds (VOCs)
      emissions from the pretreatment processes for recycling spent lithium-ion
      batteries.
AB  - The recycling of spent lithium-ion batteries brings benefits to both economic and
      environmental terms, but it can also lead to contaminants in a workshop
      environment. This study focused on metals, non-metals and volatile organic
      compounds generated by the discharging and dismantling pretreatment processes
      which are prerequisite for recycling spent lithium-ion batteries. After
      discharging in NaCl solution, metal contents in supernate and concentrated liquor
      were detected. Among results of condition #2, #3, #4 and #5, supernate and
      concentrated liquor contain high levels of Na, Al, Fe; middle levels of Co, Li,
      Cu, Ca, Zn; and low levels of Mn, Sn, Cr, Zn, Ba, K, Mg, V. The Hg, Ag, Cr and V
      are not detected in any of the analyzed supernate. 10wt% NaCl solution was a
      better discharging condition for high discharge efficiency, less possible harm to
      environment. To collect the gas released from dismantled LIB belts, a set of gas
      collecting system devices was designed independently. Two predominant organic
      vapour compounds were dimethyl carbonate (4.298mgh(-1)) and tert-amylbenzene
      (0.749mgh(-1)) from one dismantled battery cell. To make sure the concentrations
      of dimethyl carbonate under recommended industrial exposure limit (REL) of
      100mgL(-1), for a workshop on dismantling capacity of 1000kg spent LIBs, the
      minimum flow rate of ventilating pump should be 235.16m(3)h(-1). 

PMID- 27021698
TI  - Updating and testing of a Finnish method for mixed municipal solid waste
      composition studies.
AB  - More efficient recycling of municipal solid waste (MSW) is an essential
      precondition for turning Europe into a circular economy. Thus, the recycling of
      MSW must increase significantly in several member states, including Finland. This
      has increased the interest in the composition of mixed MSW. Due to increased
      information needs, a method for mixed MSW composition studies was introduced in
      Finland in order to improve the national comparability of composition study
      results. The aim of this study was to further develop the method so that it
      corresponds to the information needed about the composition of mixed MSW and
      still works in practice. A survey and two mixed MSW composition studies were
      carried out in the study. According to the responses of the survey, the
      intensification of recycling, the landfill ban on organic waste and the producer
      responsibility for packaging waste have particularly influenced the need for
      information about the composition of mixed MSW. The share of biowaste in mixed
      MSW interested the respondents most. Additionally, biowaste proved to be the
      largest waste fraction in mixed MSW in the composition studies. It constituted
      over 40% of mixed MSW in both composition studies. For these reasons, the
      classification system of the method was updated by further defining the
      classifications of biowaste. The classifications of paper as well as paperboard
      and cardboard were also updated. The updated classification system provides more
      information on the share of avoidable food waste and waste materials suitable for
      recycling in mixed MSW. The updated method and the information gained from the
      composition studies are important in ensuring that the method will be adopted by
      municipal waste management companies and thus used widely in Finland. 

PMID- 27021701
TI  - Popliteal Artery Pseudoaneurysm After Total Knee Arthroplasty.
AB  - BACKGROUND: Popliteal artery pseudoaneurysm is a rare complication after total
      knee arthroplasty. Early recognition is imperative in its management to prevent
      the subsequent development of compartment syndrome and soft tissue ischemia. The
      aim of this study was to evaluate the complication rate, recognition, and
      management of symptomatic popliteal artery pseudoaneurysm after total knee
      arthroplasty. METHODS: Between January 2004 and October 2014, 7937 consecutive
      total knee arthroplasties were identified from the Theatre Management (Ormis)
      System and cross-referenced against 1304 radiology reports containing the key
      words "popliteal" and "aneurysm' identified from the Patient Archiving
      Communication System. RESULTS: Seven patients (0.088%) were found to have had a
      symptomatic popliteal artery pseudoaneurysm. The median (range) interval between
      total knee arthroplasty and the radiological diagnosis of a pseudoaneurysm was 15
      (7-27) days. Popliteal artery pseudoaneurysm was diagnosed on duplex imaging (n =
      4), arteriogram (n = 2), and computed tomography angiogram (n = 1). Fasciotomies
      were undertaken in 3 patients. CONCLUSION: The complication rate of popliteal
      artery pseudoaneurysm was comparable to the literature. Recognition was
      identified as a problem. An appreciation of the mechanisms of injury and an
      awareness of this potential complication among orthopedic surgeons are imperative
      in reducing the complication rate and interval to diagnosis. Popliteal artery
      pseudoaneurysm should be included in the differential diagnosis for patients with
      a clinical presentation of postoperative compartment syndrome or deep vein
      thrombosis, and examination of the popliteal pulse should be undertaken early.

PMID- 27021703
TI  - PSA ANNUAL MEETING 2011.

PMID- 27021702
TI  - Geriatrics Education Team Model Results in Sustained Geriatrics Training in 15
      Residency and Fellowship Programs and Scholarship.
AB  - Caring for the growing elderly population will require specialty and subspecialty
      physicians who have not completed geriatric medicine fellowship training to
      participate actively in patient care. To meet this workforce demand, a
      sustainable approach to integrating geriatrics into specialty and subspecialty
      graduate medical education training is needed. This article describes the use of
      a geriatrics education team (GET) model to develop, implement, and sustain
      specialty-specific geriatrics curricula using a systematic process of team
      formation and needs assessment through evaluation, with a unique focus on
      developing curricular interventions that are meaningful to each specialty and
      satisfy training, scholarship, and regulatory requirements. The GET model and
      associated results from 15 specialty residency and fellowship training programs
      over a 4-year period include 93% curriculum sustainability after initial
      implementation, more than half of the programs introducing additional geriatrics
      education, and more than 80% of specialty GETs fulfilling their scholarship
      requirements through their curriculum dissemination. Win-wins and barriers
      encountered in using the GET model, along with the model's efficacy in curriculum
      development, sustainability, and dissemination, are summarized. 

PMID- 27021699
TI  - Homoeologs: What Are They and How Do We Infer Them?
AB  - The evolutionary history of nearly all flowering plants includes a
      polyploidization event. Homologous genes resulting from allopolyploidy are
      commonly referred to as 'homoeologs', although this term has not always been used
      precisely or consistently in the literature. With several allopolyploid genome
      sequencing projects under way, there is a pressing need for computational methods
      for homoeology inference. Here we review the definition of homoeology in
      historical and modern contexts and propose a precise and testable definition
      highlighting the connection between homoeologs and orthologs. In the second part,
      we survey experimental and computational methods of homoeolog inference,
      considering the strengths and limitations of each approach. Establishing a
      precise and evolutionarily meaningful definition of homoeology is essential for
      understanding the evolutionary consequences of polyploidization.

PMID- 27021704
TI  - CHARACTERIZATION OF THE PARMALES: MUCH MORE THAN THE RESOLUTION OF A TAXONOMIC
      ENIGMA.

PMID- 27021700
TI  - Differentiation of Spiral Ganglion-Derived Neural Stem Cells into Functional
      Synaptogenetic Neurons.
AB  - Spiral ganglion neurons (SGNs) are usually damaged in sensorineural hearing loss.
      SGN-derived neural stem cells (NSCs) have been identified and proposed to
      differentiate into neurons to replace damaged SGNs. However, it remains obscure
      whether SGN-NSC-derived neurons (ScNs) are electrophysiologically functional and
      possess the capability to form neural connections. Here, we found that SGN
      derived cells demonstrated NSC characteristics and differentiated into SGN-like
      glutamatergic neurons. Neurotrophins significantly increased neuronal
      differentiation and neurite length of ScNs. Patch clamp recording revealed that
      ScNs possessed SGN-like NaV and HCN channels, suggesting electrophysiological
      function. FM1-43 staining and synaptic protein immunofluorescence showed ScNs
      possess the ability to form neural connections. Astrocyte-conditioned medium was
      able to stimulate ScNs to express synaptic proteins. These data suggested that
      neurotrophins are able to stimulate postnatal SGN-NSCs to differentiate into
      functional glutamatergic ScNs with the capability to form synaptic connections in
      vitro.

PMID- 27021705
TI  - SEX RATIO VARIATION IN THE LESSONIA NIGRESCENS COMPLEX (LAMINARIALES,
      PHAEOPHYCEAE): EFFECT OF LATITUDE, TEMPERATURE, AND MARGINALITY(1).
AB  - Little is known about variation of sex ratio, the proportion of males to females,
      in natural populations of seaweed, though it is a major determinant of the mating
      system. The observation of sexual chromosomes in kelps suggested that sex is
      partly genetically determined. However, it is probably not purely genetic since
      the sex ratio can be modified by environmental factors such as salinity or
      temperature. In this paper, sex ratio variation was studied in the kelp Lessonia
      nigrescens Bory complex, recently identified as two cryptic species occurring
      along the Chilean coast: one located north and the other south of the
      biogeographic boundary at latitude 29 degrees -30 degrees  S. The life cycle of
      L. nigrescens is characterized by an alternation of microscopic haploid
      gametophytic individuals and large macroscopic fronds of diploid sporophytes. The
      sex ratio was recorded in progenies from 241 sporophytic individuals collected
      from 13 populations distributed along the Chilean coast in order (i) to examine
      the effect of an environmental gradient coupled with latitude, and (ii) to
      compare marginal populations to central populations of the two species. In
      addition, we tested the hypothesis that the sex ratios of the two cryptic species
      would be affected differently by temperature. First, our results demonstrate that
      sex ratio seems to be mainly genetically determined and temperature can
      significantly modify it. Populations of the northern species showed a lower
      frequency of males at 14 degrees C than at 10 degrees C, whereas populations of
      the southern species showed the opposite pattern. Second, both species displayed
      an increased variation in sex ratio at the range limits. This greater variation
      at the margins could be due either to differential mortality between sexes or to
      geographic parthenogenesis (asexual reproduction). 

PMID- 27021706
TI  - INTERACTIVE EFFECTS OF SALINITY AND TEMPERATURE ON PLANOZYGOTE AND CYST FORMATION
      OF ALEXANDRIUM MINUTUM (DINOPHYCEAE) IN CULTURE(1).
AB  - The factors regulating dinoflagellate life-cycle transitions are poorly
      understood. However, their identification is essential to unravel the causes
      promoting the outbreaks of harmful algal blooms (HABs) because these blooms are
      often associated with the formation and germination of sexual cysts.
      Nevertheless, there is a lack of knowledge on the factors regulating planozygote
      cyst transitions in dinoflagellates due to the difficulties of differentiating
      planozygotes from vegetative stages. In the present study, two different
      approaches were used to clarify the relevance of environmental factors on
      planozygote and cyst formation of the toxic dinoflagellate Alexandrium minutum
      Halim. First, the effects of changes in initial phosphate (P) and nitrate (N)
      concentrations in the medium on the percentage of planozygotes formed were
      examined using flow cytometry. Second, two factorial designs were used to
      determine how salinity (S), temperature (T), and the density of the initial cell
      inoculum (I) affect planozygote and resting-cyst formation. These experiments led
      to the following conclusions: 1. Low P/N ratios seem to induce gamete expression
      because the percentage of planozygotes recorded in the absence of added phosphate
      (-P) was significantly higher than that obtained in the absence of added nitrogen
      (-N), or when the concentrations of both nitrogen and phosphate were 20 times
      lower (N/20 + P/20). 2. Salinity (S) and temperature (T) strongly affected both
      planozygote and cyst formation, as sexuality in the population increased
      significantly as salinity decreased and temperatures increased. S, T combinations
      that resulted in no significant cyst formation were, however, favorable for
      vegetative growth, ruling out the possibility of negative effects on cell
      physiology. 3. The initial cell density is thought to be important for sexual
      cyst formation by determining the chances of gamete contact. However, the
      inoculum concentrations tested did not explain either planozygote formation or
      the appearance of resting cysts. 

PMID- 27021707
TI  - INTERSTRAIN VARIABILITY IN PHYSIOLOGY AND GENETICS OF HETEROSIGMA AKASHIWO
      (RAPHIDOPHYCEAE) FROM THE WEST COAST OF NORTH AMERICA(1).
AB  - High levels of intraspecific variability are often associated with HAB species,
      and this variability is likely an important factor in their competitive success.
      Heterosigma akashiwo (Hada) Hada ex Y. Hara et M. Chihara is an ichthyotoxic
      raphidophyte capable of forming dense surface-water blooms in temperate coastal
      regions throughout the world. We isolated four strains of H. akashiwo from fish
      killing northern Puget Sound blooms in 2006 and 2007. By assessing numerous
      aspects of biochemistry, physiology, and toxicity, we were able to describe
      distinct ecotypes that may be related to isolation location, source population,
      or bloom timing. Contrasting elements among strains were cell size, maximum
      growth and photosynthesis rates, tolerance of low salinities, amino acid use, and
      toxicity to the ciliate grazer Strombidinopsis acuminatum (Faure-Fremiet). In
      addition, the rDNA sequences and chloroplast genome of each isolate were
      examined, and while all rDNA sequences were identical, the chloroplast genome
      identified differences among the strains that tracked differences in ecotype. H.
      akashiwo strain 07A, which was isolated from an unusual spring bloom, had a
      significantly higher maximum potential photosynthesis rate (28.7 pg C . cell(-1) 
      . h(-1) ) and consistently exhibited the highest growth rates. Strains 06A and
      06B were not genetically distinct from one another and were able to grow on the
      amino acids glutamine and alanine, while the other two strains could not. Strain
      07B, which is genetically distinct from the other three strains, exhibited the
      only nontoxic effect. Thus, molecular tools may support identification, tracking,
      and prediction of strains and/or ecotypes using distinctive chloroplast gene
      signatures. 

PMID- 27021708
TI  - IMPACTS OF MESOGRAZERS ON EPIPHYTE AND ENDOPHYTE GROWTH ASSOCIATED WITH
      CHEMICALLY DEFENDED MACROALGE FROM THE WESTERN ANTARCTIC PENINSULA: A MESOCOSM
      EXPERIMENT(1).
AB  - It has been hypothesized that the extensive mesograzer community along the
      western Antarctic Peninsula regulates epiphytic algae as well as emergent
      filaments from endophytic species. Should grazing limit growth of fouling or
      potentially pathogenic microphytes, then Antarctic macrophytes may actually
      benefit from the remarkably high densities of mesograzer amphipods that occur in
      these waters. Although initially counterintuitive, the negative impacts of
      epi/endophyte fouling may outweigh stresses caused by limited amphipod grazing on
      chemically defended macrophytes by reducing stress from endo/epiphyte biomass. If
      so, then alleviating mesograzing stress should result in significant increases in
      endo/epiphytic biomass. To test this hypothesis, a mesocosm experiment was
      conducted. Individuals representing four common species of Antarctic macroalgae
      were placed in flow-through seawater mesocosms. Amphipods were added to five
      mesocosms at simulated natural densities, while the other five remained herbivore
      free. At the end of 7 weeks, endo/epiphytic growth on individual macrophytes was
      quantified. Most species of macroalgae demonstrated noticeably higher instances
      of endophyte coverage, epiphytic diversity, and diatom colonization in consumer
      free mesocosms than in the presence of amphipods. These data suggest that
      macroalgae along the western Antarctic Peninsula rely on grazers to control
      populations of potentially harmful epiphytes. We hypothesize that the chemically
      defended macroalgal flora lives in mutualism with high densities of mesograzers,
      providing amphipods with shelter from predation while continually being cleaned
      of potentially harmful endo/epiphytes. 

PMID- 27021709
TI  - INVOLVEMENT OF MICROCYSTINS AND COLONY SIZE IN THE BENTHIC RECRUITMENT OF THE
      CYANOBACTERIUM MICROCYSTIS (CYANOPHYCEAE)(1).
AB  - The benthic recruitment of Microcystis was simulated in vitro in order to
      characterize the colonies of Microcystis recruited and to study the impact of
      intracellular and extracellular microcystins (MCs), and the influence of colony
      size on the recruitment process. We observed recruitment dynamics consisting of a
      lag phase followed by a peak and then a return to low recruitment rates, mainly
      controlled by passive resuspension throughout the experiment, and by
      physiological processes during the recruitment peak. Ninety-seven percent of the
      Microcystis colonies recruited were <160 MUm in maximum length, and their cells
      contained much greater amounts of MCs (0.26 +/- 0.14 pg eq microcystin leucine
      arginine variant [MC-LR] . cell(-1) ) than those in benthic colonies (0.021 +/-
      0.004 pg eq MC-LR . cell(-1) ). The MC content of recruited Microcystis varied
      significantly over time and was not related to changes in the proportion of
      potentially toxic genotypes, determined using real-time PCR. On the other hand,
      the changes in MC content in the potentially toxic Microcystis recruited were
      closely and negatively correlated with recruitment dynamics; the lowest MC
      contents corresponded to high recruitment rates, and the highest MC contents
      corresponded to low recruitment rates. Thus, depending on temperature and light
      conditions, these variations are thought to result from the selection of various
      subpopulations from among the smallest and the most toxic of the initial benthic
      population. Adding purified MC-LR to experimental treatments led to a decreased
      recruitment of Microcystis and more specifically of mcyB genotypes. 

PMID- 27021710
TI  - A PHYLOGENETIC APPROACH TO THE ESTIMATION OF PHYTOPLANKTON TRAITS(1).
AB  - The quantitative characterization of the ecology of individual phytoplankton taxa
      is essential for model resolution of many aspects of aquatic ecosystems. Existing
      literature cannot directly parameterize all phytoplankton taxa of interest, as
      many traits and taxa have not been sampled. However, valuable clues on the value
      of traits are found in the evolutionary history of species and in common
      correlations between traits. These two resources were exploited with an existing,
      statistically consistent method built upon evolutionary concepts. From a new data
      set with >700 observations on freshwater phytoplankton traits and a qualitative
      phytoplankton phylogeny, estimates were derived for the size, growth rate,
      phosphate affinity, and susceptibility to predation of 277 phytoplankton types,
      from evolutionary ancestors to present-day species. These estimates account
      simultaneously for phylogenetic relationships between types, as imposed by the
      phylogeny, and approximate power-law relationships (e.g., allometric scaling
      laws) between traits, as reconstructed from the data set. Results suggest that
      most phytoplankton traits are to some extent conserved in evolution: cross
      validation demonstrated that the use of phylogenetic information significantly
      improves trait value estimates. By providing trait value estimates as well as
      uncertainties, these results could benefit most quantitative studies involving
      phytoplankton. 

PMID- 27021711
TI  - LINKING TIME-DEPENDENT CARBON-FIXATION EFFICIENCIES IN DUNALIELLA TERTIOLECTA
      (CHLOROPHYCEAE) TO UNDERLYING METABOLIC PATHWAYS(1).
AB  - The chl-specific short-term (14) C-based production (P(b) ) measurement is a
      widely used tool to understand phytoplankton responses to environmental stresses.
      However, among the metabolic consequences of these stresses is variability in
      lifetimes of newly fixed carbon that cause P(b) to range between chl-specific net
      primary production (NPP*) and chl-specific gross photosynthetic electron flow
      that is available for carbon reduction () depending on growth rate. To
      investigate the basis for this discrepancy, photosynthate utilization was
      characterized in Dunaliella tertiolecta Butcher grown at three different growth
      rates in N-limited chemostats. P(b) was measured throughout a 2 min to 24 h time
      course and showed clear growth-rate-dependent differences in lifetimes of newly
      fixed carbon. (14) C pulse-chase experiments revealed differences in patterns of
      carbon utilization between growth rates. At high growth rate, the majority of
      (14) C was initially fixed into polysaccharide and lipid, but the relative
      contribution of each labeled biochemical pool to the total label changed over 24
      h. In fast-growing cells, labeled polysaccharides decreased 50%, while labeled
      lipids increased over the first 4 h. At low growth rate, (14) C was initially
      incorporated primarily into protein, but the contribution of labeled protein to
      the total label increased over the next 24 h. Together, time-resolved
      measurements of P(b) and cellular NAD and NADP content suggest an enhanced role
      for alternative dissipation pathways at very low growth rate. Findings of this
      study contribute to an integrated understanding of growth-rate-dependent shifts
      in metabolic processes from photosynthesis to net growth. 

PMID- 27021712
TI  - PHOTOPROTECTION OF SEA-ICE MICROALGAL COMMUNITIES FROM THE EAST ANTARCTIC PACK
      ICE(1).
AB  - All photosynthetic organisms endeavor to balance energy supply with demand. For
      sea-ice diatoms, as with all marine photoautotrophs, light is the most important
      factor for determining growth and carbon-fixation rates. Light varies from
      extremely low to often relatively high irradiances within the sea-ice
      environment, meaning that sea-ice algae require moderate physiological plasticity
      that is necessary for rapid light acclimation and photoprotection. This study
      investigated photoprotective mechanisms employed by bottom Antarctic sea-ice
      algae in response to relatively high irradiances to understand how they acclimate
      to the environmental conditions presented during early spring, as the light
      climate begins to intensify and snow and sea-ice thinning commences. The sea-ice
      microalgae displayed high photosynthetic plasticity to increased irradiance, with
      a rapid decline in photochemical efficiency that was completely reversible when
      placed under low light. Similarly, the photoprotective xanthophyll pigment
      diatoxanthin (Dt) was immediately activated but reversed during recovery under
      low light. The xanthophyll inhibitor dithiothreitol (DTT) and state transition
      inhibitor sodium fluoride (NaF) were used in under-ice in situ incubations and
      revealed that nonphotochemical quenching (NPQ) via xanthophyll-cycle activation
      was the preferred method for light acclimation and photoprotection by bottom sea
      ice algae. This study showed that bottom sea-ice algae from the east Antarctic
      possess a high level of plasticity in their light-acclimation capabilities and
      identified the xanthophyll cycle as a critical mechanism in photoprotection and
      the preferred means by which sea-ice diatoms regulate energy flow to PSII. 

PMID- 27021713
TI  - SHORT- AND LONG-TERM EFFECTS OF ELEVATED CO2 ON PHOTOSYNTHESIS AND RESPIRATION IN
      THE MARINE MACROALGA HIZIKIA FUSIFORMIS (SARGASSACEAE, PHAEOPHYTA) GROWN AT LOW
      AND HIGH N SUPPLIES(1).
AB  - The short-term and long-term effects of elevated CO2 on photosynthesis and
      respiration were examined in cultures of the marine brown macroalga Hizikia
      fusiformis (Harv.) Okamura grown under ambient (375 MUL . L(-1) ) and elevated
      (700 MUL . L(-1) ) CO2 concentrations and at low and high N availability. Short
      term exposure to CO2 enrichment stimulated photosynthesis, and this stimulation
      was maintained with prolonged growth at elevated CO2 , regardless of the N levels
      in culture, indicating no down-regulation of photosynthesis with prolonged growth
      at elevated CO2 . However, the photosynthetic rate of low-N-grown H. fusiformis
      was more responsive to CO2 enrichment than that of high-N-grown algae. Elevation
      of CO2 concentration increased the value of K1/2 (Ci) (the half-saturation
      constant) for photosynthesis, whereas high N supply lowered it. Neither short
      term nor long-term CO2 enrichment had inhibitory effects on respiration rate,
      irrespective of the N supply, under which the algae were grown. Under high-N
      growth, the Q10 value of respiration was higher in the elevated-CO2 -grown algae
      than the ambient-CO2 -grown algae. Either short- or long-term exposure to CO2
      enrichment decreased respiration as a proportion of gross photosynthesis (Pg) in
      low-N-grown H. fusiformis. It was proposed that in a future world of higher
      atmospheric CO2 concentration and simultaneous coastal eutrophication, the
      respiratory carbon flux would be more sensitive to changing temperature. 

PMID- 27021714
TI  - FLUORESCENCE EMISSION SPECTRA OF MARINE AND BRACKISH-WATER ECOTYPES OF FUCUS
      VESICULOSUS AND FUCUS RADICANS (PHAEOPHYCEAE) REVEAL DIFFERENCES IN LIGHT
      HARVESTING APPARATUS(1).
AB  - The Bothnian Sea in the northerly part of the Baltic Sea is a geologically recent
      brackish-water environment, and rapid speciation is occurring in the algal
      community of the Bothnian Sea. We measured low-temperature fluorescence emission
      spectra from the Bothnian Sea and the Norwegian Sea ecotypes of Fucus vesiculosus
      L., a marine macroalga widespread in the Bothnian Sea. Powdered, frozen thallus
      was used to obtain undistorted emission spectra. The spectra were compared with
      spectra measured from the newly identified species Fucus radicans Bergstrom et L.
      Kautsky, which is a close relative of F. vesiculosus and endemic to the Bothnian
      Sea. The spectrum of variable fluorescence was used to identify fluorescence
      peaks originating in PSI and PSII in this chl c-containing alga. The spectra
      revealed much higher PSII emission, compared to PSI emission, in the Bothnian Sea
      ecotype of F. vesiculosus than in F. radicans or in the Norwegian Sea ecotype of
      F. vesiculosus. The results suggest that more light-harvesting chl a/c proteins
      serve PSII in the Bothnian Sea ecotype of F. vesiculosus than in the two other
      algal strains. Treatment of the Bothnian Sea ecotype of F. vesiculosus in high
      salinity (10, 20, and 35 practical salinity units) for 1 week did not lead to
      spectral changes, indicating that the measured features of the Bothnian Sea F.
      vesiculosus are stable and not simply a direct result of exposure to low
      salinity. 

PMID- 27021715
TI  - MONO- AND DIGALACTOSYLDIACYLGLYCEROL COMPOSITION OF RAPHIDOPHYTES
      (RAPHIDOPHYCEAE): A MODERN INTERPRETATION USING POSITIVE-ION ELECTROSPRAY/MASS
      SPECTROMETRY/MASS SPECTROMETRY(1).
AB  - Raphidophyte algae (Raphidophyceae) can be divided according to pigment
      composition and plastid ancestry into two categories, brown- and green-pigmented
      taxa. We sought to examine if there are any biochemical differences in plastid
      lipid composition between the two groups. To this end, the composition and
      positional distribution of fatty acids of the chloroplast lipids, mono- and
      digalactosyldiacylglycerol (MGDG and DGDG, respectively), were examined using
      positive-ion electrospray/mass spectrometry (ESI/MS) and electrospray/mass
      spectrometry/mass spectrometry (ESI/MS/MS). Brown-pigmented strains from the
      genera Chattonella, Fibrocapsa, and Heterosigma primarily consisted of 20:5/18:4
      (sn-1/sn-2) MGDG and 20:5/18:4 DGDG, while isolates of the green-pigmented
      raphidophyte Gonyostomum semen (Ehrenb.) Diesing contained these as well as
      18:3/18:4 MGDG and DGDG, thus underscoring its green algal plastid lineage.
      Although previously unseen without the regiochemical information provided by
      ESI/MS/MS, Chattonella subsalsa Biecheler possessed 20:5/18:3 DGDG as a major
      form, a potential biosynthetic intermediate in the production of 20:5/18:4 DGDG.
      These results provide a modern interpretation of the fatty acid regiochemistry of
      MGDG and DGDG. 

PMID- 27021716
TI  - DIMETHYLSULFONIOPROPIONATE STORAGE IN PHAEOCYSTIS (PRYMNESIOPHYCEAE) SECRETORY
      VESICLES(1).
AB  - Despite the global importance of dimethylsulfoniopropionate (DMSP)/dimethyl
      sulfide (DMS) and their role in climate regulation, little is known about the
      mechanisms of their production and storage in Phaeocystis sp., a major
      contributor of DMS in polar areas. Phaeocystis secretes polymer microgels, by
      regulated exocytosis, remaining in condensed phase while stored in secretory
      vesicles (Chin et al. 2004). In secretory cells, vesicles also store small
      molecules, which are released during exocytosis. Here, we demonstrated that DMSP
      and DMS were stored in the secretory vesicles of Phaeocystis antarctica G. Karst.
      They were trapped within a polyanionic gel matrix, which prevented an accurate
      measurement of their concentration in the absence of a chelating agent such as
      EDTA. Understanding the production and the export mechanisms of DMSP and DMS into
      seawater is important because of the impact the cellular and extracellular pools
      of these highly relevant biogeochemical metabolites have on the environment. The
      pool of total DMSP in the presence of Phaeocystis may be underestimated by as
      much as half. Obtaining accurate budget measurements is the first step toward
      gaining a better understanding of key issues related to the DMS ocean-air
      interaction and the effect of phytoplankton DMS production on climate change. 

PMID- 27021717
TI  - SURFACE INTERACTIONS OF THE EPIPHYTIC MACROALGA HINCKSIA MITCHELLIAE
      (PHAEOPHYCEAE) WITH THE SHOALGRASS HALODULE WRIGHTII (CYMODOCEACEAE)(1).
AB  - Meadows of Halodule wrightii (Cymodoceaceae) underwent a decline in a tidal flat
      located at Paranagua Bay (Parana, SE Brazil). This decline appeared to be related
      to an overgrowth of the epiphytic macroalga Hincksia mitchelliae (Harv.) P. C.
      Silva (Phaeophyceae). In order to characterize the type of epiphytism between the
      alga and its plant host, we compared two samples from the beginning and end of
      the algal overgrowth via electron and optical microscopes. The investigation
      revealed that at both sampling periods, there was an epiphytism of type II, which
      is due to an infection of epiphytes strongly attached to the surface of the host
      but not associated to any apparent direct host-tissue damage. The presence of
      plasmodesmata between the cells of Hincksia only in the late stage of the host
      epiphyte interaction indicated a change in the vegetative organization of
      Hincksia in relation to its host to improve nutrient absorption and distribution
      through the epiphyte cells. This is the first report on plasmodesmata in H.
      mitchelliae. The proposed mechanisms with which the algal epiphytes lead
      seagrasses to death are shadowing by adhesion on Halodule surface and disruption
      of its osmoregulatory system. Our findings have implications for the conservation
      and management strategies of seagrass ecosystems. 

PMID- 27021718
TI  - DISTINGUISHING MULTIPLE LINEAGES OF PEDIASTRUM DUPLEX WITH MORPHOMETRICS AND A
      PROPOSAL FOR LACUNASTRUM GEN. NOV(1).
AB  - Accurately defining species boundaries in the green algae (Chlorophyta) is
      integral for studies of biodiversity and conservation, water-quality assessments,
      and the use of particular species as paleoindicators. Recent molecular
      phylogenetic and SEM analyses of the family Hydrodictyaceae (Chlorophyta)
      resolved three phylogenetic lineages of isolates with the Pediastrum duplex Meyen
      1829 phenotype. The present study employed analyses of cell shape and cell wall
      ultrastructure to determine if the three lineages possessing the P. duplex
      morphotype were distinguishable. Only one of the groups, containing isolates with
      the P. duplex var. gracillimum West et G. S. West phenotype, was shown to be
      morphologically distinct from the other two P. duplex groups. The erection of a
      new genus, Lacunastrum, is proposed to recognize this group as a separate taxon. 

PMID- 27021719
TI  - A CHARACEAN THALLUS WITH ATTACHED GYROGONITES AND ASSOCIATED FOSSIL CHAROPHYTES
      FROM THE MAASTRICHTIAN OF THE EASTERN PYRENEES (CATALONIA, SPAIN)(1).
AB  - The new species Clavatoraxis microcharophorus is described from the Lower
      Maastrichtian of the Eastern Pyrenees (Catalonia, Spain). Microchara sp.
      gyrogonites were found in anatomical connection with this thallus, attached to
      bract-cell rosettes and coated by a structural tunica, formed by an expanded
      bract cell. This is a feature unknown in extant characeans, which only display
      lime incrustations similar to tunicae in extremely alkaline and well-illuminated
      environments. This is the first time that a complete fossil characean is
      described. The attribution of characean vegetative remains to the genus
      Clavatoraxis shows that this genus is not exclusive of clavatoraceans as
      previously thought. The taphonomic study of C. microcharophorus sp. nov. and
      associated fossil charophytes, along with sedimentological and microfacies
      analyses, has enabled us to characterize the habitat of this species in the
      Maastrichtian lake of Vallcebre. They grew forming meadows, and their remains
      were deposited in the poorly oxygenated lake bottom, where they were well
      preserved. A number of other characeans and porocharaceans were living in
      shallower belts. This was the case for Peckichara sp. and Munieria grambasti in
      the freshwater lacustrine meadows. Another species, Feistiella malladae, was
      found parautochthonous in brackish lakes. 

PMID- 27021720
TI  - ISOLATION AND CHARACTERIZATION OF PARMALES
      (HETEROKONTA/HETEROKONTOPHYTA/STRAMENOPILES) FROM THE OYASHIO REGION, WESTERN
      NORTH PACIFIC(1).
AB  - A small siliceous species of marine phytoplankton, order Parmales (Heterokonta),
      was isolated and characterized for the first time with the aid of a fluorescent
      silicon tracer 2-(4-pyridyl)-5-([4-(2-dimethylaminoethylaminocarbamoyl)
      methoxy]phenyl)oxazole (PDMPO). This dye was easily detected by clear
      fluorescence in newly produced silica cell plates. Our isolate was surrounded by
      eight smooth plates without any ornamentation, suggesting a similarity to
      Triparma laevis B. C. Booth. TEM observation showed the typical ultrastructure of
      photosynthetic heterokontophytes; with two chloroplast endoplasmic reticulate
      membranes, a girdle lamella, three thylakoid lamellae, and mitochondrion with
      tubular cristae. Molecular phylogenetic analyses of SSU rDNA and rbcL genes
      showed that the parmalean alga was within the bolidophycean clade of autotrophic
      naked flagellates and a sister group of diatoms. HPLC analysis detected chl a, c1
      + c2 , and c3 ; fucoxanthin; and diadinoxanthin as major photosynthetic
      pigments, and a composition that is shared with Bolidophyceae and diatoms.
      Together, these data indicate a close evolutionary relationship between Parmales,
      Bolidophyceae, and diatoms. The PDMPO-staining procedure should accelerate
      isolation of other Parmales species, helping to establish their diversity and
      aiding quantitative study of their role in oceanic processes. 

PMID- 27021721
TI  - MOLECULAR PHYLOGENETIC RELATIONSHIPS IN THE FRESHWATER FAMILY HYDRODICTYACEAE
      (SPHAEROPLEALES, CHLOROPHYCEAE), WITH AN EMPHASIS ON PEDIASTRUM DUPLEX(1).
AB  - The freshwater green algal family Hydrodictyaceae (Sphaeropleales, Chlorophyta)
      has traditionally consisted of four coenobial genera, Pediastrum Meyen 1829,
      Hydrodictyon Roth 1797, Sorastrum Kutzing 1845, and Euastropsis Lagerheim1894.
      Two recent molecular phylogenetic studies demonstrated the need for reevaluation
      of the generic and species boundaries in this morphology-rich family. This study
      expands the previous work to include phylogenetic analyses of 103 ingroup
      isolates representing North America, Europe, and Australia, with an emphasis on
      the common and geographically widespread species Pediastrum duplex. Nucleotide
      sequence data were collected from the nuclear LSU (26S rDNA) and the chloroplast
      RUBISCO LSU (rbcL) genes, totaling >3,000 aligned characters. The 26S and rbcL
      data sets were analyzed using maximum-likelihood (ML) and Bayesian phylogenetic
      methods. In addition, SEM was used to examine the wall morphology of a majority
      of the isolates. The results supported previous indications that the P. duplex
      Meyen 1829 morphotype is nonmonophyletic and resolved some previously ambiguous
      relationships recovered in earlier phylogenetic estimations using fewer isolates.
      These new data allowed testing of the recent taxonomic revisions of the family
      that split Pediastrum into five genera. Some of the previous revisions by
      Buchheim et al. (2005) were well supported (erection of Stauridium and
      Monactinus), while others were not (Pediastrum, Pseudopediastrum,
      Parapediastrum). 

PMID- 27021722
TI  - POLYPHYLY OF CHAETOPHORA AND STIGEOCLONIUM WITHIN THE CHAETOPHORALES
      (CHLOROPHYCEAE), REVEALED BY SEQUENCE COMPARISONS OF NUCLEAR-ENCODED SSU rRNA
      GENES(1).
AB  - Previously published molecular phylogenetic analyses of the Chaetophorales
      (Chlorophyceae) suffered from limited taxon sampling (six genera with only a
      single species per genus). To test the monophyly of species-rich genera, and to
      analyze the phylogenetic relationships among families and genera in the
      Chaetophorales, we determined nuclear-encoded SSU rDNA sequences from 30 strains
      of Chaetophorales, performed phylogenetic analyses using various methods, and
      screened clades for support by unique molecular synapomorphies in the SSU rRNA
      secondary structure. The Schizomeridaceae and the weakly supported
      Aphanochaetaceae were recovered as basal lineages. The derived family
      Chaetophoraceae diverged into two clades: the "Uronema clade" containing
      unbranched filaments, and a sister clade designated as "branched Chaetophoraceae"
      comprising Chaetophora, Stigeoclonium, Draparnaldia, Caespitella, and
      Fritschiella. Although some terminal clades corresponded to genera described
      (e.g., Caespitella and Draparnaldia), other clades were in conflict with
      traditional taxonomic designations. Especially, the genera Stigeoclonium and
      Chaetophora were shown to be polyphyletic. The globose species Chaetophora
      elegans was unrelated to lobate Chaetophora spp. (e.g., Chaetophora lobata).
      Since the original description of Chaetophora referred to a lobate thallus
      organization, the latter clade represented Chaetophora sensu stricto. In
      consequence, C. lobata was designated as lectotype of Chaetophora. Two
      Stigeoclonium species, Stigeoclonium farctum Berthold and
      Stigeoclonium'Longipilus', diverged independently from the type species of
      Stigeoclonium, Stigeoclonium tenue (C. Agardh) Kutz. These results indicated that
      some commonly used taxonomic characters are either homoplasious or plesiomorphic
      and call for a reevaluation of the systematics of the Chaetophorales using novel
      morphological and molecular approaches. 

PMID- 27021723
TI  - SPECIES BOUNDARIES IN THE TOXIC DINOFLAGELLATE PROROCENTRUM LIMA (DINOPHYCEAE,
      PROROCENTRALES), BASED ON MORPHOLOGICAL AND PHYLOGENETIC CHARACTERS(1).
AB  - Wild and cultured specimens of Prorocentrum lima (Ehrenb.) F. Stein from 26
      widely different areas in 13 countries were examined in order to determine
      consistent characters for delimiting species boundaries in this taxon. The
      morphological characters valve shape, valve size, valve ornamentation, number and
      shape of valve pores, number and shape of marginal pores, and periflagellar
      platelets were observed using LM and SEM, and two molecular genetic regions were
      sequenced. We identified stable morphological characters that were consistent
      among wild specimens and all cultures, which were valve shape, valve
      ornamentation, and number and arrangement of periflagellar platelets. All
      cultures of P. lima identified by these characters formed a monophyletic group in
      phylogenetic analyses based on the two genes, which, however, included the
      species Prorocentrum arenarium. P. arenarium was determined to be within the
      range of morphological variation of P. lima, and therefore we synonymize the two
      taxa. Within this monophyletic group, P. lima was divided into several subclades
      in the all phylogenetic analyses. There were no morphological characters
      specifically related to any one subclade. The subclades appeared to correlate
      broadly to sample collection regions, suggesting that geographically separated
      populations may have become genetically distinct within this epi-benthic species.
      We have emended species boundaries in P. lima. 

PMID- 27021724
TI  - ORGANIC CARBON SUPPLEMENTATION OF STERILIZED MUNICIPAL WASTEWATER IS ESSENTIAL
      FOR HETEROTROPHIC GROWTH AND REMOVING AMMONIUM BY THE MICROALGA CHLORELLA
      VULGARIS(1).
AB  - Heterotrophic growth of the microalga Chlorella vulgaris Beij. in synthetic as
      well as sterilized municipal wastewater of a nonindustrialized city was measured.
      The city wastewater contained high levels of ammonium and nitrate, medium levels
      of phosphate, and low levels of nitrite and organic molecules and could not
      support heterotrophic growth of C. vulgaris. Evaluation of 11 known carbon
      sources for this microalga that were added to standard synthetic wastewater
      containing the same levels of nitrogen and phosphorus as the municipal wastewater
      revealed that the best carbon sources for heterotrophic growth were Na-acetate
      and d-glucose. These provided the highest growth rates and the largest removal of
      ammonium. Growth increased with concentration of the supplement to an optimum at
      0.12 M Na-acetate. This carbon source was consumed completely within 10 d of
      incubation. Higher concentrations inhibited the growth of C. vulgaris. The
      microalgal populations under heterotrophic growth conditions were one level of
      magnitude higher than that under autotrophic growth conditions that served as a
      comparison. No growth occurred in the dark in the absence of a carbon source. Na
      acetate was superior to d-glucose. In municipal wastewater, when Na-acetate or d
      glucose was added, C. vulgaris significantly enhanced ammonium removal under
      heterotrophic conditions, and its capacity was equal to ammonium removal under
      autotrophic growth conditions. This study showed that sterilized wastewater can
      be treated by C. vulgaris under heterotrophic conditions if supplemented with the
      appropriate organic carbon source for the microalgae. 

PMID- 27021725
TI  - PHYCOBILIN CONTENT OF THE CONCHOCELIS PHASE OF ALASKAN PORPHYRA (BANGIALES,
      RHODOPHYTA) SPECIES: RESPONSES TO ENVIRONMENTAL VARIABLES(1).
AB  - Variations of pigment content in the microscopic conchocelis stage of four
      Alaskan Porphyra species were investigated in response to environmental
      variables. Conchocelis filaments were cultured under varying conditions of
      irradiance and nutrient concentrations for up to 60 d at 11 degrees C and 30 psu
      salinity. Results indicate that conchocelis filaments contain relatively high
      concentrations of phycobilins under optimal culture conditions. Phycobilin
      pigment production was significantly affected by irradiance, nutrient
      concentration, and culture duration. For Porphyra abbottiae V. Krishnam.,
      Porphyra sp., and Porphyra torta V. Krishnam., maximal phycoerythrin (63.2-95.1
      mg . g dwt(-1) ) and phycocyanin (28.8-64.8 mg . g dwt(-1) ) content generally
      occurred at 10 MUmol photons . m(-2)  . s(-1) , f/4-f/2 nutrient concentration
      after 10-20 d of culture. Whereas for Porphyra hiberna S. C. Lindstrom et K. M.
      Cole, the highest phycoerythrin (73.3 mg . g dwt(-1) ) and phycocyanin (70.2 mg .
      g dwt(-1) ) content occurred at 10 MUmol photons . m(-2)  . s(-1) , f nutrient
      concentration after 60 d in culture. Under similar conditions, the different
      species showed significant differences in pigment content. P. abbottiae had
      higher phycoerythrin content than the other three species, and P. hiberna had the
      highest phycocyanin content. P. torta had the lowest phycobilin content. 

PMID- 27021726
TI  - Human Exposure to Wastewater-Derived Pharmaceuticals in Fresh Produce: A
      Randomized Controlled Trial Focusing on Carbamazepine.
AB  - Fresh water scarcity has led to increased use of reclaimed wastewater as an
      alternative and reliable source for crop irrigation. Beyond microbiological
      safety, concerns have been raised regarding contamination of reclaimed wastewater
      by xenobiotics including pharmaceuticals. This study focuses on carbamazepine, an
      anticonvulsant drug which is ubiquitously detected in reclaimed wastewater,
      highly persistent in soil, and taken up by crops. In a randomized controlled
      trial we demonstrate that healthy individuals consuming reclaimed wastewater
      irrigated produce excreted carbamazepine and its metabolites in their urine,
      while subjects consuming fresh water-irrigated produce excreted undetectable or
      significantly lower levels of carbamazepine. We also report that the
      carbamazepine metabolite pattern at this low exposure level differed from that
      observed at therapeutic doses. This "proof of concept" study demonstrates that
      human exposure to xenobiotics occurs through ingestion of reclaimed wastewater
      irrigated produce, providing real world data which could guide risk assessments
      and policy designed to ensure the safe use of wastewater for crop irrigation.

PMID- 27021727
TI  - Internet use by pregnant women seeking pregnancy-related information: a
      systematic review.
AB  - BACKGROUND: The Internet has become one of the most popular sources of
      information for health consumers and pregnant women are no exception. The primary
      objective of this review was to investigate the ways in which pregnant women used
      the Internet to retrieve pregnancy-related information. METHODS: We conducted a
      systematic review to answer this question. In November 2014, electronic
      databases: Scopus, Medline, PreMEDLINE, EMBASE, CINAHL and PubMed were searched
      for papers with the terms "Internet"; "pregnancy"; "health information seeking",
      in the title, abstract or as keywords. Restrictions were placed on publication to
      within 10 years and language of publication was restricted to English.
      Quantitative studies were sought, that reported original research and described
      Internet use by pregnant women. RESULTS: Seven publications met inclusion
      criteria and were included in the review. Sample size ranged from 182 - 1347
      pregnant women. The majority of papers reported that women used the Internet as a
      source of information about pregnancy. Most women searched for information at
      least once a month. Fetal development and nutrition in pregnancy were the most
      often mentioned topics of interest. One paper included in this review found that
      women with higher education were three times more likely to seek advice than
      women with less than a high school education, and also that single and
      multiparous women were less likely to seek advice than married and nulliparous
      women. The majority of women found health information on the Internet to be
      reliable and useful. CONCLUSION: Most women did not discuss the information they
      retrieved from the Internet with their health providers. Thus, health providers
      may not be aware of potentially inaccurate information or mistaken beliefs about
      pregnancy, reported on the Internet. Future research is needed to address this
      issue of potentially unreliable information.

PMID- 27021728
TI  - Prolactin, EGFR, vimentin and alpha-actin profiles in elderly rat prostate
      subjected to steroid hormonal imbalance.
AB  - The aim of this study was to characterize and relate the prolactin (PR),
      epidermal growth factor receptor (EGFR), alpha-actin and vimentin
      immunoreactivity in the prostate of elderly rats subjected to steroid hormonal
      imbalance. Senile and young rats were divided into the young group (YNG), the
      senile group (SE), the castrated group (CAS), the estrogen-deficient group (ED),
      the castrated+estrogen group (CASE), and the estrogen-deficient+androgen group
      (EDTEST). PR and EGFR increased in the estrogen and androgen ablation groups. In
      addition, EGFR influenced the immunolocalization by changing it from the
      prostatic stroma to the epithelium in elderly rats. Hormone ablation in elderly
      rats, not only related to androgen but also estrogen, led to increased stromal
      EGFR immunolocalization. The alpha-actin pattern decreased in the groups with
      estrogenic imbalance. Moreover, vimentin increased in the senile and estrogen
      deficient group. To conclude, we can suggest that EGFR contributed towards the
      proliferative process in the prostate, by means however, of different mechanisms,
      considering the androgenic and estrogenic pathways. Also, our results indicated
      that prolactin could be activated not only in an androgen-independent pathway but
      also in an estrogen independent pathway. Finally, PR and vimentin
      immunolocalization increase, in the prostatic stroma in the group showing
      estrogenic ablation, could be one of the factors which contribute to the reactive
      stroma formation. 

PMID- 27021729
TI  - Design of a plasmonic micromotor for enhanced photo-remediation of polluted
      anaerobic stagnant waters.
AB  - A motor plasmonic photocatalyst (MPP) is developed to promote photocatalysis in
      an anaerobic stagnant environment. The MPP is fabricated through the newly
      developed nano/micromotor fabrication method: template-assisted aqueous phase
      synthesis. With the help of H2O2 (fuel), the solar photocatalytic efficiency of
      the MPP can be enhanced more than 110 times. 

PMID- 27021730
TI  - The oxygen reduction reaction (ORR) on reduced metals: evidence for a unique
      relationship between the coverage of adsorbed oxygen species and adsorption
      energy.
AB  - Using chronoamperometry and voltammetry at oxide-free microelectrodes in non
      adsorbing electrolyte, KClO4, we investigated the reduction of oxygen containing
      species which adsorb at potentials below those where oxides are grown
      electrochemically when the electrode is exposed to dissolved oxygen. Their
      coverage is found to vary with the metal substrate as follows, Ni > Cu > Pt > Ag,
      and is negligible on Au microdiscs. This dependence is consistent with the
      adsorption energy of atomic oxygen for the respective metals predicted by DFT.
      Furthermore the adsorption energies derived from the stripping peak potentials
      for the different metals agree very well with those predicted by the DFT
      calculations. We exploit the oxygen coverage differences between Pt, Pt0.9Rh0.1
      and Pt0.9Ir0.1 microdiscs to predict the adsorption energy of these species on
      the Pt alloys and demonstrate a clear correlation between the metal activity
      towards the ORR and the charge associated with the reduction of the adsorbed
      oxygen species. In effect the coverage - adsorption energy relationship turns the
      charge associated with the reduction of the adsorbed oxygen species into a
      descriptor of the electrode activity towards the ORR. This study provides new
      insight into the oxygen reduction reaction and offers a new methodology to
      investigate low temperature fuel cell ORR catalysts.

PMID- 27021731
TI  - Risk Factors for Intimate Partner Violence: A Comparison of Antisocial and Family
      Only Perpetrators.
AB  - Subtyping male perpetrators of intimate partner violence (IPV) based on their
      generality of violence could facilitate the difficult task of matching
      perpetrator subtype with efficient risk management strategies. As such, the aim
      of the present study was to compare antisocial and family-only male perpetrators
      of interpersonal violence in terms of (a) demographic and legal characteristics,
      (b) risk factors for violence, and (c) assessed risk and the importance of
      specific risk factors for violence. A quantitative design was used in this
      retrospective register study on data obtained from the Swedish police. Risk
      assessments performed with the Swedish version of the Brief Spousal Assault Form
      for the Evaluation of Risk (B-SAFER) and police registers were used. A sample of
      657 male alleged IPV perpetrators were classified as antisocial ( n = 341) or
      family-only ( n = 316) based on their generality of violence. The results showed
      that the antisocial perpetrators were significantly younger, as well as more
      psychologically abusive. Antisocial perpetrators also had significantly more
      present risk factors for IPV, and were assessed with a significantly higher risk
      for acute and severe or deadly IPV, compared with the family-only perpetrators.
      The subtypes also evidenced unique risk factors with a significant impact on
      elevated risk for acute and severe or deadly such violence. Key findings in the
      present study concerned the subtypes evidencing unique risk factors increasing
      the risk for acute and severe or deadly IPV. Major implications of this study
      include the findings of such unique "red flag" risk factors for each subtype. To
      prevent future IPV, it is vital for the risk assessor to be aware of these red
      flags when making decisions about risk, as well as risk management strategies.

PMID- 27021732
TI  - Longitudinal Investigation of Depression, Intimate Partner Violence, and Supports
      Among Vulnerable Families.
AB  - Intimate partner violence (IPV) affects nearly 12 million individuals and their
      families each year in the United States. Many negative outcomes are associated
      with IPV, with depression being one of the most prevalent mental health problems.
      Most previous studies on IPV have used cross-sectional designs to examine the
      potential protective effects of support on depression. The current study fills
      this gap by conducting a longitudinal investigation of the roles of social
      support and family resources on depression among caregivers of young children.
      The study sample consisted of 548 female caregivers. Findings suggest that among
      those with an IPV history, those with higher social support reported lower
      depressive symptoms than those with less social support. No significant
      interaction was found for family resources and IPV. Rather, family resources had
      a main effect on depressive symptoms with no differential impact based on IPV
      status. Findings suggest the importance of connecting vulnerable families to
      supports such as social support and family resources to help mitigate depressive
      symptoms. Future research should consider the underlying mechanisms of social
      support as a protective factor among IPV victims with depression.

PMID- 27021733
TI  - Tested at Last: How DNA Evidence in Untested Rape Kits Can Identify Offenders and
      Serial Sexual Assaults.
AB  - An increasing number of U.S. law enforcement agencies have disclosed that they
      have large numbers of untested sexual assault kits (SAKs; also called "rape
      kits") in police property storage. Whether previously untested SAKs should be
      tested for DNA evidence has been the subject of considerable public debate. To
      inform policy and practice regarding rape kit testing, the current study tested a
      sample of 900 previously unsubmitted SAKs from Detroit, Michigan, and documented
      the DNA forensic testing outcomes associated with those kits. We assessed how
      many SAKs yielded DNA profiles eligible for upload into CODIS (Combined DNA Index
      System), the federal DNA criminal database; how many resulted in a DNA match
      (termed a "CODIS hit"); and how many of those hits were associated to other
      sexual assault crimes (i.e., serial sexual assault hits). Overall, there were 259
      CODIS hits, 69 of which had DNA matches to another sexual assault case. The
      potential utility of a DNA profile and CODIS hit may vary depending on whether
      offender was known or unknown to the victim, so we examined these outcomes
      separately for SAKs associated with stranger- and non-stranger-perpetrated sexual
      assaults. We also present six case study examples of how DNA testing and CODIS
      hits helped identify serial sexual assaults in both stranger and non-stranger
      sexual assault cases. Implications for rape kit testing policies are discussed.

PMID- 27021734
TI  - Managing Conflicts in Urban Communities: Youth Attitudes Regarding Gun Violence.
AB  - Gun violence remains a pressing public health concern, especially in high-risk
      urban environments. Community-level violence intervention efforts are being
      mounted in cities across the United States to prevent and reduce the most severe
      forms of violence. There is growing evidence to suggest the effectiveness of the
      Safe Streets Program/ Cure Violence as a community-based intervention to reduce
      homicides and shootings. The mechanism underlying the reductions in community
      violence is theorized to be linked with changes in attitudes toward violence as
      well as shifts in social norms related to violence and retaliation, but there are
      few tools to assess these domains. This preliminary investigation sought to
      establish the metric properties of the Survey on Attitudes About Guns and
      Shootings (SAGAS) with the goal of providing an empirical measure of attitudes
      and community-level norms. Males aged 18 to 24 were surveyed using the SAGAS in
      two high-violence communities in Baltimore, Maryland, using street intercept
      methodology. We found acceptable reliability and validity metrics for the SAGAS.
      Reliability and validity of the SAGAS were assessed using internal consistency
      and a latent class analysis with violent behavior outcomes. The internal
      consistency of the total scale was in the extensive range (alpha = .70-.79) and
      the internal consistency of the factors was in the exemplary range (alpha >=
      .80). In addition, latent classes of attitudes were predictive of being arrested
      or being shot. Future studies will examine if rates of violence decrease in
      neighborhoods targeted by the Safe Streets Program and the mediating role of
      attitudes toward gun violence using the SAGAS.

PMID- 27021735
TI  - Impact of Violence and Relationship Abuse on Grades of American Indian/Alaska
      Native Undergraduate College Students.
AB  - Violence and relationship abuse are pervasive public health problems that have a
      range of negative effects, with exceptionally high prevalence among ethno-racial
      minority youth. This study assesses the prevalence of these types of violence
      among American Indian/Alaska Native (AI/AN) students and examines the impact of
      victimization on academic performance of AI/AN and non-AI/AN student populations
      using self-reported college health survey data. Results show that students who
      identified fully or partially as AI/AN reported markedly higher rates of all
      types of violence/abuse than did other students, and students who had experienced
      violence/abuse had lower grade point averages (GPAs) compared with those who had
      not. Recommendations for future research and direct practice with AI/AN students
      are discussed.

PMID- 27021736
TI  - Lessons Learned: Conducting Research With Victims Portrayed in Sexual Abuse
      Images and Their Parents.
AB  - Victims portrayed in sexual abuse images may be resistant to participate in
      research because of embarrassment or shame due to the sensitive nature and
      potential permanency of images. No studies we are aware of explore reactions to
      participating in research after this type of crime. Telephone interviews were
      conducted with convenience samples of parents ( n = 46) and adolescents who were
      victims of child sexual abuse ( n = 11; some of whom were portrayed in sexual
      abuse images), and online surveys were completed by adult survivors depicted in
      abuse images ( N = 133). The first lesson was that few agencies tracked this type
      of crime. This lack of tracking raises the question as to what types of data
      should be collected and tracked as part of an investigation. The second lesson
      was that few victims at the two participating agencies had been portrayed in
      sexual abuse images (4%-5%). The third lesson was that once possible cases were
      identified, we found relatively high percentages of consent to contact and
      interview completions. This implies that researchers and service providers should
      not be hesitant about conducting research after an investigation of child sexual
      abuse. The fourth lesson was that the vast majority of participants reported not
      being upset by the questions. We hope that the data presented here will encourage
      agencies to reconsider the types of data being tracked and will encourage
      researchers to conduct in-depth research with populations that are often
      difficult to reach to continue improving the professional response to child
      victimization.

PMID- 27021737
TI  - Environmental Unpredictability in Childhood Is Associated With Anxious Romantic
      Attachment and Intimate Partner Violence Perpetration.
AB  - Human life history theory describes how resources are allocated among conflicting
      life tasks, including trade-offs concerning reproduction. The current research
      investigates the unique importance of environmental unpredictability in childhood
      in association with romantic attachment, and explores whether objective or
      subjective measures of environmental risk are more informative for testing life
      history hypotheses. We hypothesize that (1) unpredictability in childhood will be
      associated with greater anxious attachment, (2) anxious attachment will be
      associated with intimate partner violence (IPV) perpetration, and (3) anxious
      attachment will mediate the relationship between unpredictability in childhood
      and IPV perpetration. In two studies (total n = 391), participants in a
      heterosexual, romantic relationship completed self-report measures of childhood
      experiences, romantic attachment, and IPV perpetration. Study 1 provides support
      for Hypothesis 1. Hypothesis 1 is replicated only for men, but not women, in
      Study 2. Results of Study 2 provide support for Hypothesis 2 for men and women,
      and Hypothesis 3 was supported for men but not women. The findings contribute to
      the literature addressing the association of environmental risk in childhood on
      adult romantic relationship outcomes.

PMID- 27021739
TI  - The Role of Socio-Economic Status in Adoption of Coping Strategies Among
      Adolescents Against Domestic Violence.
AB  - In the current study, researchers explored different types of coping strategies
      such as problem-focused coping, emotion-focused coping, and non-constructive
      coping of adolescents witnessing and experiencing domestic violence. Furthermore,
      they tried to find out the association of socio-economic status with coping
      strategies against domestic violence in family sphere. A cross-sectional survey
      was conducted with 210 adolescents of both sexes, aged 13 to 18 years in
      Hafizabad city using multistage sampling technique. Multivariate analysis was
      used to find out the association between adolescents' resistance and resilience
      strategies against domestic violence. The information was collected through a
      structured interview schedule. This study revealed that age, gender, parents'
      education, and family income were major factors that influenced the adoption of
      coping strategy among adolescents. Overall, the study suggested that adolescents
      were being victimized of various forms of domestic violence frequently in
      Pakistan, which needs to be addressed on immediate basis through policies and
      programs by integrating the social institutions of family and education. Findings
      of the study can enable parents to nurture and support the developmental needs of
      children in their care. It can help youth in defending themselves from extreme
      violent behavior adopters and preventing them from becoming the perpetrators of
      the domestic violence.

PMID- 27021738
TI  - The Roles of Family Factors and Relationship Dynamics on Dating Violence
      Victimization and Perpetration Among College Men and Women in Emerging Adulthood.
AB  - Using data from the International Dating Violence Study, this study examined the
      roles of early socialization, family social structure, and relationship dynamics
      factors on physical aggression in dating among U.S. college students in emerging
      adulthood. The interaction effects between these three domains of interest (early
      socialization, family social structure, and relationship dynamics) were explored
      to understand the underlying mechanisms that influenced victimization and
      perpetration in dating. In general, we found that family and relational variables
      associated with dating victimization and perpetration were fairly similar. Among
      the early socialization variables, experience of childhood neglect and having
      witnessed domestic violence were significantly related to victimization and
      perpetration. Living in a two-parent household appeared to exert a protective
      effect, although associations with parental education were not statistically
      significant. Furthermore, the participants were more likely to experience
      victimization or impose aggression in dating relationships which were
      characterized by conflicts, distress, dominance, or psychological aggression.
      Overall, for the participants who came from a two-parent household, dominance in
      dating was linked to less violence. When the participants faced higher levels of
      psychological aggression, adverse early socialization factors were associated
      with higher levels of dating violence victimization and perpetration. Research
      and practice implications were discussed.

PMID- 27021740
TI  - Attitudes Toward Sexual Violence Survivors: Differences Across Professional
      Sectors in Kenya and the Democratic Republic of the Congo.
AB  - Sexual violence survivors who decide to report their assault interact with health
      care, law enforcement, and legal and judicial professionals. Professionals'
      attitudes about sexual violence and survivors play an important role in caring
      for survivors and in the pursuit of justice. Despite evidence showing the
      relationship between service provider beliefs and survivor outcomes, relatively
      little is known about professionals' beliefs about sexual violence or their
      attitudes toward sexual violence survivors. Between June 2012 and December 2014,
      our study examined the beliefs and attitudes of 181 professionals from the health
      care, legal, and law enforcement sectors in the Eastern Democratic Republic of
      the Congo (DRC) and the Rift Valley region of Kenya, areas with a high prevalence
      of sexual violence. To determine correlates of beliefs and attitudes about sexual
      violence and sexual violence survivors, multiple logistic regression models were
      adjusted for demographic and occupational characteristics. Respondents who agreed
      that survivors got what they deserved (7%) or that survivors should feel ashamed
      (9%) were the minority, while those who would be willing to care for a family
      member with a history of sexual violence (94%) were the majority. Profession was
      significantly associated with beliefs and attitudes about sexual violence and
      survivors. Law enforcement professionals were more likely than health
      professionals and lawyers to indicate that survivors should feel ashamed. Our
      findings suggest a need for interventions that adequately address potentially
      harmful beliefs and attitudes of some professionals serving sexual violence
      survivors.

PMID- 27021741
TI  - The Association of Domestic Violence and Social Resources With Functioning in an
      Adult Trauma-Affected Sample Living in Kurdistan, Northern Iraq.
AB  - Domestic violence (DV) and other experienced trauma types increase the risk for
      impaired functioning. Access to social resources may provide a buffer to existing
      risks and allow individuals to continue and build functioning. This cross
      sectional study investigated the direct effects of DV and access to social
      resources (perceived social support, social integration, and frequency of social
      contact), as well as their potential interactive effects, on daily functioning
      among 894 male and female trauma survivors who attended primary care clinics in
      Kurdistan, Iraq in 2009 and 2010. Experiencing DV was not associated with
      functioning for males ( p=.15) or females ( p=.60), suggesting that in the
      context of a trauma-affected sample, the experience of DV may not significantly
      increase the risk for functional impairment. Greater amounts of social
      integration were associated with less functional impairment among males ( p<.01)
      and females ( p<.05); social integration was associated with less functional
      impairment among males only ( p<.01); and frequency of social contact was
      associated with less functional impairment among females only ( p<.05),
      indicating that the association between social resource type and functioning
      differed by gender. Social resources had a stronger effect on functioning among
      men compared to women. Among males who experienced DV, social integration was the
      only social resource associated with less functional impairment ( p<.01); among
      male trauma survivors who did not experience DV, social support was the only
      resource associated with less functional impairment ( p<.01). Further
      investigation into these associations is warranted to inform intervention
      strategies for survivors of DV and other traumas in post-conflict settings.

PMID- 27021742
TI  - One-pot synthesis and in-vitro anticancer evaluation of 5-(2'-indolyl)thiazoles.
AB  - A series of 5-(2'-indolyl)thiazoles were synthesized and evaluated for their
      cytotoxicity against selected human cancer cell lines. The reaction of thioamides
      3 with 3-tosyloxypentane-2,4-dione 4 led to in situ formation of 5-acetylthiazole
      5 which upon treatment with arylhydrazines 6 in polyphosphoric acid resulted in
      the formation of 5-(2'-indolyl)thiazoles 2. Among the synthesized 5-(2'
      indolyl)thiazoles, compounds 2d-f, and 2h exhibited encouraging anticancer
      activity and also selectivity towards particular cell lines (IC50 = 10-30 MUM).
      Further studies on the SAR of compound 2e may result in good anticancer activity.

PMID- 27021743
TI  - Rescue Effects and Underlying Mechanisms of Intragland Shh Gene Delivery on
      Irradiation-Induced Hyposalivation.
AB  - Irreversible hypofunction of salivary glands is common in head and neck cancer
      survivors treated with radiotherapy and can only be temporarily relieved with
      current treatments. We found in an inducible sonic hedgehog (Shh) transgenic
      mouse model that transient activation of the Hedgehog pathway after irradiation
      rescued salivary gland function in males by preserving salivary stem/progenitor
      cells and parasympathetic innervation. To translate these findings into feasible
      clinical application, we evaluated the effects of Shh gene transfer to salivary
      glands of wild-type mice on irradiation-induced hyposalivation. Shh or control
      GFP gene was delivered by noninvasive retrograde ductal instillation of
      corresponding adenoviral vectors. In both male and female mice, Shh gene delivery
      efficiently activated Hedgehog/Gli signaling, and significantly improved
      stimulated saliva secretion and preserved saliva-producing acinar cells after
      irradiation. In addition to preserving parasympathetic innervation through
      induction of neurotrophic factors, Shh gene delivery also alleviated the
      irradiation damage of the microvasculature, likely via inducing angiogenic
      factors, but did not expand the progeny of cells responsive to Hedgehog/Gli
      signaling. These data indicate that transient activation of the Hedgehog pathway
      by gene delivery is promising to rescue salivary function after irradiation in
      both sexes, and the Hedgehog/Gli pathway may function mainly in cell
      nonautonomous manners to achieve the rescue effect. 

PMID- 27021744
TI  - Challenges in Using MCDA for Reimbursement Decisions on New Medicines?

PMID- 27021745
TI  - Multiple Criteria Decision Analysis for Health Care Decision Making--Emerging
      Good Practices: Report 2 of the ISPOR MCDA Emerging Good Practices Task Force.
AB  - Health care decisions are complex and involve confronting trade-offs between
      multiple, often conflicting objectives. Using structured, explicit approaches to
      decisions involving multiple criteria can improve the quality of decision making.
      A set of techniques, known under the collective heading, multiple criteria
      decision analysis (MCDA), are useful for this purpose. In 2014, ISPOR established
      an Emerging Good Practices Task Force. The task force's first report defined
      MCDA, provided examples of its use in health care, described the key steps, and
      provided an overview of the principal methods of MCDA. This second task force
      report provides emerging good-practice guidance on the implementation of MCDA to
      support health care decisions. The report includes: a checklist to support the
      design, implementation and review of an MCDA; guidance to support the
      implementation of the checklist; the order in which the steps should be
      implemented; illustrates how to incorporate budget constraints into an MCDA;
      provides an overview of the skills and resources, including available software,
      required to implement MCDA; and future research directions. 

PMID- 27021746
TI  - Estimating the Cost-Effectiveness of Implementation: Is Sufficient Evidence
      Available?
AB  - BACKGROUND: Timely implementation of recommended interventions can provide health
      benefits to patients and cost savings to the health service provider. Effective
      approaches to increase the implementation of guidance are needed. Since
      investment in activities that improve implementation competes for funding against
      other health generating interventions, it should be assessed in term of its costs
      and benefits. OBJECTIVE: In 2010, the National Institute for Health and Care
      Excellence released a clinical guideline recommending natriuretic peptide (NP)
      testing in patients with suspected heart failure. However, its implementation in
      practice was variable across the National Health Service in England. This study
      demonstrates the use of multi-period analysis together with diffusion curves to
      estimate the value of investing in implementation activities to increase uptake
      of NP testing. METHODS: Diffusion curves were estimated based on historic data to
      produce predictions of future utilization. The value of an implementation
      activity (given its expected costs and effectiveness) was estimated. Both a
      static population and a multi-period analysis were undertaken. RESULTS: The value
      of implementation interventions encouraging the utilization of NP testing is
      shown to decrease over time as natural diffusion occurs. Sensitivity analyses
      indicated that the value of the implementation activity depends on its efficacy
      and on the population size. CONCLUSIONS: Value of implementation can help inform
      policy decisions of how to invest in implementation activities even in situations
      in which data are sparse. Multi-period analysis is essential to accurately
      quantify the time profile of the value of implementation given the natural
      diffusion of the intervention and the incidence of the disease.

PMID- 27021747
TI  - Cost-Effectiveness of Incobotulinumtoxin-A with Flexible Treatment Intervals
      Compared to Onabotulinumtoxin-A in the Management of Blepharospasm and Cervical
      Dystonia.
AB  - BACKGROUND: Incobotulinumtoxin-A (Xeomin((r)), Merz Pharmaceuticals, Sydney, New
      South Wales) is a formulation of botulinum neurotoxin type A that is free of
      complexing proteins. OBJECTIVE: To assess the cost-effectiveness of
      incobotulinumtoxin-A administered with flexible treatment intervals compared to
      onabotulinumtoxin-A (Botox((r)), Sydney, New South Wales) in blepharospasm and
      cervical dystonia from the perspective of Australian health care providers.
      METHODS: A Markov state transition model was developed to perform a cost-utility
      analysis to compare the cost and health benefits of incobotulinumtoxin-A to that
      of onabotulinumtoxin-A. The cost-utility analysis compared incobotulinumtoxin-A
      treatment, given at minimum intervals of 6 weeks and maximum intervals of 20
      weeks, with onabotulinumtoxin-A treatment, given at minimum intervals of 12 weeks
      and maximum intervals of 20 weeks. The Markov model consisted of three health
      states and followed patients in weekly cycles for 5 years. Only direct health
      care costs associated with the acquisition and administration of type A botulinum
      neurotoxins were included. Utility values were derived from a prospective, open
      labeled cohort study. The primary outcome measure was the incremental cost per
      quality-adjusted life-year. Univariate and probabilistic sensitivity analyses
      were conducted. RESULTS: Incobotulinumtoxin-A was cost-effective compared to
      onabotulinumtoxin-A in both blepharospasm and cervical dystonia, with an
      incremental cost/quality-adjusted life-year gained of A$ 25,588 and A$ 23,794,
      respectively. CONCLUSIONS: Incobotulinumtoxin-A administered at flexible
      treatment intervals determined by the needs of the patient was found to be a cost
      effective treatment option when compared to the administration of
      onabotulinumtoxin-A in the Australian health care system. The option to
      administer incobotulinumtoxin-A according to the needs of the patient resulted in
      patients experiencing symptoms for a fewer number of weeks compared to
      onabotulinumtoxin-A given at minimum 12-week intervals.

PMID- 27021748
TI  - The Cost-Effectiveness of Prostate Cancer Detection with the Use of Prostate
      Health Index.
AB  - BACKGROUND: Clinical trial results suggested that prostate-specific antigen (PSA)
      screening can reduce prostate cancer mortality. Nevertheless, because the
      specificity of the PSA test for cancer detection is low, it leads to many
      negative biopsies. The Beckman Coulter Prostate Health Index (PHI) testing
      demonstrates improved specificity compared with the PSA-only screening and
      therefore may improve the cost-effectiveness of prostate cancer detection.
      OBJECTIVE: To examine the cost-effectiveness of adding PHI testing to improve
      cancer detection for men with elevated serum PSA. METHODS: A microsimulation
      model, based on the results of the European Randomized Study of Screening for
      Prostate Cancer trial, was used to evaluate the effects of PSA screening and PHI
      reflex testing. We predicted the numbers of prostate cancers, negative biopsies,
      deaths, quality-adjusted life-years gained, and cost-effectiveness of both PSA
      (cutoff 3 ng/mL) and PHI (cutoff 25) testing methods for a European population,
      screened from age 50 to 75 years at 4-year intervals. RESULTS: When the PHI test
      was added to the PSA screening, for men with a PSA between 3 and 10 ng/mL, the
      model predicted a 23% reduction in negative biopsies. This would lead to a 17%
      reduction in costs for diagnostics and 1% reduction in total costs for prostate
      cancer. The cost-effectiveness (3.5% discounted) was 11% better. Limitations
      found were the modeling assumptions on the sensitivity and specificity of PHI by
      tumor stage and cutoff values. CONCLUSIONS: Compared with PSA-only screening, the
      use of a PHI test can substantially reduce the number of negative biopsies and
      improve the cost-effectiveness of prostate cancer detection.

PMID- 27021749
TI  - Examining the Value of Menopausal Symptom Relief Among US Women.
AB  - BACKGROUND: Menopausal symptoms can cause significant distress to women, yet
      little is known about the value women place on these symptoms. METHODS: In April
      2013, 3397 US women, aged 40 to 69 years, completed an online survey that
      included 30 paired comparisons. Specifically, respondents were shown two
      menopausal symptoms described using the Patient-Reported Outcomes Version of the
      Common Terminology Criteria for Adverse Events and asked, "Which do you prefer?"
      From their choices, we estimated a generalized linear model to assess the values
      women place on symptom relief in terms of quality-adjusted life-years (QALYs).
      RESULTS: Approximately half the respondents (1753 of 3397 [52%]) always preferred
      a reduced lifespan (up to 90 days) instead of experiencing menopausal symptoms at
      their worst for 30 days. For most of the symptoms (248 of 263 [94%]), including
      low-grade events, QALYs were significantly reduced (P < 0.05). The value women
      placed on relief ranged widely by symptom domain: the relief from depression,
      problems with memory, headache, pain in abdomen, problems with anger, and
      vomiting were the most valuable. CONCLUSIONS: Overall, the value women place on
      menopausal symptom relief is surprisingly high. As the first national study to
      directly ask women about their preferences and to estimate the value of
      menopausal symptom relief on a QALY scale, this work provides critical evidence
      for health outcomes research in midlife women and can be applied in the
      evaluation of treatments that reduce or eliminate menopausal symptoms. This work
      also provides proof-of-concept for an approach to value Patient-Reported Outcomes
      Version of the Common Terminology Criteria for Adverse Events responses on a QALY
      scale.

PMID- 27021750
TI  - Comprehensively Measuring Health-Related Subjective Well-Being: Dimensionality
      Analysis for Improved Outcome Assessment in Health Economics.
AB  - BACKGROUND: Allocation of inevitably limited financial resources for health care
      requires assessment of an intervention's effectiveness. Interventions likely
      affect quality of life (QOL) more broadly than is measurable with commonly used
      health-related QOL utility scales. In line with the World Health Organization's
      definition of health, a recent Delphi procedure showed that assessment needs to
      put more emphasis on mental and social dimensions. OBJECTIVE: To identify the
      core dimensions of health-related subjective well-being (HR-SWB) for a new, more
      comprehensive outcome measure. METHODS: We formulated items for each domain of an
      initial Delphi-based set of 21 domains of HR-SWB. We tested these items in a
      large sample (N = 1143) and used dimensionality analyses to find a smaller number
      of latent factors. RESULTS: Exploratory factor analysis suggested a five-factor
      model, which explained 65% of the total variance. Factors related to physical
      independence, positive affect, negative affect, autonomy, and personal growth.
      Correlations between the factors ranged from 0.19 to 0.59. A closer inspection of
      the factors revealed an overlap between the newly identified core dimensions of
      HR-SWB and the validation scales, but the dimensions of HR-SWB also seemed to
      reflect additional aspects. This shows that the dimensions of HR-SWB we
      identified go beyond the existing health-related QOL instruments. CONCLUSIONS: We
      identified a set of five key dimensions to be included in a new, comprehensive
      measure of HR-SWB that reliably captures these dimensions and fills in the gaps
      of the existent measures used in economic evaluations.

PMID- 27021751
TI  - Improving Adherence to Cardiovascular Therapies: An Economic Evaluation of a
      Randomized Pragmatic Trial.
AB  - OBJECTIVE: Preplanned economic analysis of a pragmatic trial using electronic
      medical-record-linked interactive voice recognition (IVR) reminders for enhancing
      adherence to cardiovascular medications (i.e., statins, angiotensin-converting
      enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]). METHODS:
      Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+),
      with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on
      average. Costs to implement and deliver the intervention (from a payer
      perspective) were tracked during the trial. Medical care costs and outcomes were
      ascertained using electronic medical records. RESULTS: Per-patient intervention
      costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB,
      the incremental cost-effectiveness ratio for each percent adherence increase was
      about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+,
      respectively). For statins, the incremental cost-effectiveness ratio for each
      percent adherence increase was about 7 times higher with IVR+ than with IVR ($6
      and $43 for IVR and IVR+, respectively). Considering potential cost offsets from
      reduced cardiovascular events, the probability of breakeven was the highest for
      UC, but the IVR-based interventions had a higher probability of breakeven for
      subgroups with a baseline low-density lipoprotein (LDL) level of more than 100
      mg/dl and those with two or more calls. CONCLUSIONS: We found that the use of an
      automated voice messaging system to promote adherence to ACEIs/ARBs and statins
      may be cost-effective, depending on a decision maker's willingness to pay for
      unit increase in adherence. When considering changes in LDL level and downstream
      medical care offsets, UC is the optimal strategy for the general population.
      However, IVR-based interventions may be the optimal choice for those with
      elevated LDL values at baseline.

PMID- 27021752
TI  - Cost-Effectiveness of a Collaborative Care Depression and Anxiety Treatment
      Program in Patients with Acute Cardiac Illness.
AB  - OBJECTIVE: To use data from a randomized trial to determine the cost
      effectiveness of a collaborative care (CC) depression and anxiety treatment
      program and to assess effects of the CC program on health care utilization.
      METHODS: The CC intervention's impact on health-related quality of life,
      depression-free days (DFDs), and anxiety-free days (AFDs) over the 24-week
      postdischarge period was calculated and compared with the enhanced usual care
      (EUC) condition using independent samples t tests and random-effects regression
      models. Costs for both the CC and EUC conditions were calculated on the basis of
      staff time, overhead expenses, and treatment materials. Using this information,
      incremental cost-effectiveness ratios were calculated. A cost-effectiveness
      acceptability plot was created using nonparametric bootstrapping with 10,000
      replications, and the likelihood of the CC intervention's cost-effectiveness was
      assessed using standard cutoffs. As a secondary analysis, we determined whether
      the CC intervention led to reductions in postdischarge health care utilization
      and costs. RESULTS: The CC intervention was more costly than the EUC intervention
      ($209.86 vs. $34.59; z = -11.71; P < 0.001), but was associated with
      significantly greater increases in quality-adjusted life-years (t = -2.49; P =
      0.01) and DFDs (t = -2.13; P = 0.03), but not AFDs (t = -1.92; P = 0.057). This
      translated into an incremental cost-effectiveness ratio of $3337.06 per quality
      adjusted life-year saved, $13.36 per DFD, and $13.74 per AFD. Compared with the
      EUC intervention, the CC intervention was also associated with fewer emergency
      department visits but no differences in overall costs. CONCLUSIONS: This CC
      intervention was associated with clinically relevant improvements, was cost
      effective, and was associated with fewer emergency department visits in the 24
      weeks after discharge.

PMID- 27021754
TI  - Survival or Mortality: Does Risk Attribute Framing Influence Decision-Making
      Behavior in a Discrete Choice Experiment?
AB  - OBJECTIVE: To test how attribute framing in a discrete choice experiment (DCE)
      affects respondents' decision-making behavior and their preferences. METHODS: Two
      versions of a DCE questionnaire containing nine choice tasks were distributed
      among a representative sample of the Dutch population aged 55 to 65 years. The
      DCE consisted of four attributes related to the decision regarding participation
      in genetic screening for colorectal cancer (CRC). The risk attribute included was
      framed positively as the probability of surviving CRC and negatively as the
      probability of dying from CRC. Panel mixed-logit models were used to estimate the
      relative importance of the attributes. The data of the positively and negatively
      framed DCE were compared on the basis of direct attribute ranking, dominant
      decision-making behavior, preferences, and importance scores. RESULTS: The
      majority (56%) of the respondents ranked survival as the most important attribute
      in the positively framed DCE, whereas only a minority (8%) of the respondents
      ranked mortality as the most important attribute in the negatively framed DCE.
      Respondents made dominant choices based on survival significantly more often than
      based on mortality. The framing of the risk attribute significantly influenced
      all attribute-level estimates and resulted in different preference structures
      among respondents in the positively and negatively framed data set. CONCLUSIONS:
      Risk framing affects how respondents value the presented risk. Positive risk
      framing led to increased dominant decision-making behavior, whereas negative risk
      framing led to risk-seeking behavior. Attribute framing should have a prominent
      part in the expert and focus group interviews, and different types of framing
      should be used in the pilot version of DCEs as well as in actual DCEs to estimate
      the magnitude of the effect of choosing different types of framing.

PMID- 27021753
TI  - Responsiveness to Change in PROMIS((r)) Measures among Children with Asthma: A
      Report from the PROMIS((r)) Pediatric Asthma Study.
AB  - OBJECTIVE: To compare the responsiveness to change of the Patient-Reported
      Outcomes Measurement Information System (PROMIS((r))) asthma impact, pain
      interference, fatigue, depressive symptoms, mobility, and peer relationship
      scales to a legacy scale, the Paediatric Asthma Quality of Life Questionnaire
      (PAQLQ). METHODS: Two hundred and twenty-nine child-parent dyads from public
      insurance programs were enrolled. PROMIS pediatric short forms (SFs) and the
      PAQLQ were used to measure health-related quality of life across four time points
      (T1-T4) over 2 years. The Asthma Control and Communication Instrument was used to
      measure the change in asthma control, and the Global Rating of Change (GRC) Index
      for breathing problems and overall health was used to measure the change in
      health status. Responsiveness was tested by comparing the changes in health
      related quality of life with the changes in asthma control and health status over
      time using t tests, generalized estimating equations, and relative validity
      approaches. Magnitudes of the responsiveness between the Pediatric PROMIS and
      PAQLQ were assessed through statistical significance, Cohen's d effect size (ES),
      and standardized response mean (SRM). RESULTS: The PROMIS asthma impact scale and
      all PAQLQ scales exhibited significant responsiveness (p's<0.05) and small to
      medium ES/SRM when anchored to asthma control, GRC breathing problems, and
      overall health. Relative validity, especially related to change in asthma control
      status and GRC breathing problems, was equivalent. PROMIS pain interference,
      fatigue, and mobility SFs also indicated adequate responsiveness. CONCLUSIONS:
      The PROMIS asthma impact SF indicated similar responsiveness to the PAQLQ scales.
      Due to its brevity and responsiveness, the PROMIS asthma impact SF is useful for
      clinical practice or research.

PMID- 27021755
TI  - Valuing Health Using Time Trade-Off and Discrete Choice Experiment Methods: Does
      Dimension Order Impact on Health State Values?
AB  - BACKGROUND: Health states defined by multiattribute instruments such as the
      EuroQol five-dimensional questionnaire with five response levels (EQ-5D-5L) can
      be valued using time trade-off (TTO) or discrete choice experiment (DCE) methods.
      A key feature of the tasks is the order in which the health state dimensions are
      presented. Respondents may use various heuristics to complete the tasks, and
      therefore the order of the dimensions may impact on the importance assigned to
      particular states. OBJECTIVE: To assess the impact of different EQ-5D-5L
      dimension orders on health state values. METHODS: Preferences for EQ-5D-5L health
      states were elicited from a broadly representative sample of members of the UK
      general public. Respondents valued EQ-5D-5L health states using TTO and DCE
      methods across one of three dimension orderings via face-to-face computer
      assisted personal interviews. Differences in mean values and the size of the
      health dimension coefficients across the arms were compared using difference
      testing and regression analyses. RESULTS: Descriptive analysis suggested some
      differences between the mean TTO health state values across the different
      dimension orderings, but these were not systematic. Regression analysis suggested
      that the magnitude of the dimension coefficients differs across the different
      dimension orderings (for both TTO and DCE), but there was no clear pattern.
      CONCLUSIONS: There is some evidence that the order in which the dimensions are
      presented impacts on the coefficients, which may impact on the health state
      values provided. The order of dimensions is a key consideration in the design of
      health state valuation studies.

PMID- 27021756
TI  - Preferences for Prostate Cancer Outcomes: A Comparison of the Patient
      Perspective, the General Population Perspective, and a Population at Risk for
      Prostate Cancer.
AB  - OBJECTIVE: To collect disease-specific and generic preference values for three
      populations. METHODS: Prostate cancer-specific health states were developed with
      attributes that varied across five health domains: sexual function, urinary
      function, bowel function, pain, and fear of the future. Men with prostate cancer,
      men at risk for prostate cancer, and a sample of the general population assigned
      value to 18 disease-specific health states using standard gamble (SG)
      methodology. Study participants also completed the Health Utilities Index (HUI)
      to obtain generic, community-based preference values to capture their current
      health rating. RESULTS: A total of 136 participants were enrolled (n = 43
      prostate cancer; n = 40 at risk for prostate cancer; n = 49 general population).
      Mean HUI mark 3 current health ratings: men with prostate cancer 0.75 +/- 0.260;
      men at risk for prostate cancer 0.77 +/- 0.238; general population 0.84 +/-
      0.178. Mean SG preference values ranged from 0.46 to 0.85 among men with prostate
      cancer, 0.37 to 0.75 among men at risk for prostate cancer, and 0.32 to 0.81
      among the general population group. CONCLUSIONS: In general, preference values
      for disease-specific health states using the patient perspective were higher than
      those for the general population. Generic preference values calculated from the
      HUI were higher than disease-specific preference values calculated from the SG.
      The higher values calculated from the HUI, from all three perspectives, indicate
      that a generic measure may not be sensitive enough to capture the disutility of
      prostate cancer symptoms, specifically sexual dysfunction, urinary dysfunction,
      and bowel dysfunction, which are being directly measured in the disease-specific
      health states.

PMID- 27021757
TI  - Valuing Treatments for Parkinson Disease Incorporating Process Utility:
      Performance of Best-Worst Scaling, Time Trade-Off, and Visual Analogue Scales.
AB  - OBJECTIVE: The objective of this study was to compare treatment profiles
      including both health outcomes and process characteristics in Parkinson disease
      using best-worst scaling (BWS), time trade-off (TTO), and visual analogue scales
      (VAS). METHODS: From the model comprising of seven attributes with three levels,
      six unique profiles were selected representing process-related factors and health
      outcomes in Parkinson disease. A Web-based survey (N = 613) was conducted in a
      general population to estimate process-related utilities using profile-based BWS
      (case 2), multiprofile-based BWS (case 3), TTO, and VAS. The rank order of the
      six profiles was compared, convergent validity among methods was assessed, and
      individual analysis focused on the differentiation between pairs of profiles with
      methods used. RESULTS: The aggregated health-state utilities for the six
      treatment profiles were highly comparable for all methods and no rank reversals
      were identified. On the individual level, the convergent validity between all
      methods was strong; however, respondents differentiated less in the utility of
      closely related treatment profiles with a VAS or TTO than with BWS. For TTO and
      VAS, this resulted in nonsignificant differences in mean utilities for closely
      related treatment profiles. CONCLUSIONS: This study suggests that all methods are
      equally able to measure process-related utility when the aim is to estimate the
      overall value of treatments. On an individual level, such as in shared decision
      making, BWS allows for better prioritization of treatment alternatives,
      especially if they are closely related. The decision-making problem and the need
      for explicit trade-off between attributes should determine the choice for a
      method.

PMID- 27021758
TI  - The Use of Economic Evidence to Inform Drug Pricing Decisions in Jordan.
AB  - BACKGROUND: Drug pricing is an example of a priority setting in a developing
      country with official requirements for the use of cost-effectiveness (CE)
      evidence. OBJECTIVE: To describe the role of economic evidence in drug pricing
      decisions in Jordan. METHODS: A prospective review of all applications submitted
      between November 2013 and May 2015 to the Jordan Food and Drug Association's drug
      pricing committee was carried out. All applications that involved requests for CE
      evidence were reviewed. Details on the type of study, the extent, and whether the
      evidence submitted was part of the formal deliberations were extracted and
      summarized. RESULTS: The committee reviewed a total of 1608 drug pricing
      applications over the period of the study. CE evidence was requested in only 11
      applications. The submitted evidence was of limited use to the committee due to
      concerns about quality, relevance of studies, and lack of pharmacoeconomic
      expertise. There were also no clear rules describing how CE would inform pricing
      decisions. CONCLUSIONS: Limited local data and health economic experience were
      the main barriers to the use of economic evidence in drug pricing decisions in
      Jordan. In addition, there are no official rules describing the elements and
      process by which the CE evidence would inform drug pricing decisions. This study
      summarized accumulated observations for the current use of economic evaluations
      and evidence-based decision making in Jordan. Recommendations have been proposed
      to applicants and key decision makers to enhance the role of economic evidence in
      influencing health policies and evidence-based decision making across priority
      settings.

PMID- 27021759
TI  - Evaluation of Resource Utilization and Treatment Patterns in Patients with
      Actinic Keratosis in the United States.
AB  - OBJECTIVE: To compare health care resource utilization and treatment patterns
      between patients with actinic keratosis (AK) treated with ingenol mebutate gel
      (IngMeb) and those treated with other field-directed AK therapies. METHODS: A
      retrospective, propensity-score-matched, cohort study compared refill/repeat and
      adding-on/switching patterns and outpatient visits and prescriptions (health care
      resource utilization) over 6 months in patients receiving IngMeb versus those
      receiving imiquimod, 5-fluorouracil, diclofenac sodium, and methyl
      aminolevulinate or aminolevulinic acid photodynamic therapy (MAL/ALA-PDT).
      RESULTS: The final sample analyzed included four matched treatment cohort pairs
      (IngMeb and comparator; n = 790-971 per treatment arm). Refill rates were similar
      except for imiquimod (15% vs. 9% for imiquimod and IngMeb, respectively; P <
      0.05). MAL/ALA-PDT treatment repetition rates were higher than IngMeb refill
      rates (20% vs. 10%; P < 0.05). Topical agent add-on/switch rates were comparable.
      PDT had higher switch rates than did IngMeb (5% vs. 2%; P < 0.05). The IngMeb
      cohort had a significantly lower proportion of patients with at least one AK
      related outpatient visit during the 6-month follow-up than did any other cohort:
      versus imiquimod (50% vs. 66%; P < 0.0001), versus 5-fluorouracil (50% vs. 69%; P
      < 0.0001), versus diclofenac sodium (51% vs. 56%; P = 0.034), and versus MAL/ALA
      PDT (50% vs. 100%; P < 0.0001). There were significantly fewer AK-related
      prescriptions among patients receiving IngMeb than among patients in other
      cohorts. CONCLUSIONS: Results based on the first 6 months after treatment
      initiation suggested that most field-directed AK therapies had clinically
      comparable treatment patterns except imiquimod, which was associated with higher
      refill rates, and PDT, which was associated with significantly more frequent
      treatment sessions and higher switching rates. IngMeb was also associated with
      significantly fewer outpatient visits than were other field-directed therapies.

PMID- 27021760
TI  - Expanding Health Technology Assessments to Include Effects on the Environment.
AB  - There is growing awareness of the impact of human activity on the climate and the
      need to stem this impact. Public health care decision makers from Sweden and the
      United Kingdom have started examining environmental impacts when assessing new
      technologies. This article considers the case for incorporating environmental
      impacts into the health technology assessment (HTA) process and discusses the
      associated challenges. Two arguments favor incorporating environmental impacts
      into HTA: 1) environmental changes could directly affect people's health and 2)
      policy decision makers have broad mandates and objectives extending beyond health
      care. Two types of challenges hinder this process. First, the nascent evidence
      base is insufficient to support the accurate comparison of technologies'
      environmental impacts. Second, cost-utility analysis, which is favored by many
      HTA agencies, could capture some of the value of environmental impacts,
      especially those generating health impacts, but might not be suitable for
      addressing broader concerns. Both cost-benefit and multicriteria decision
      analyses are potential methods for evaluating health and environmental outcomes,
      but are less familiar to health care decision makers. Health care is an important
      and sizable sector of the economy that could warrant closer policy attention to
      its impact on the environment. Considerable work is needed to track decision
      makers' demands, augment the environmental evidence base, and develop robust
      methods for capturing and incorporating environmental data as part of HTA. 

PMID- 27021761
TI  - Sources and Characteristics of Utility Weights for Economic Evaluation of
      Pediatric Vaccines: A Systematic Review.
AB  - BACKGROUND: Cost-effectiveness analysis of pediatric vaccines for infectious
      diseases often requires quality-of-life (utility) weights. OBJECTIVE: To
      investigate how utility weights have been elicited and used in this context.
      METHODS: A systematic review was conducted of studies published between January
      1990 and July 2013 that elicited or used utility weights in cost-effectiveness
      analyses of vaccines for pediatric populations. The review focused on vaccines
      for 17 infectious diseases and is presented following the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. RESULTS: A
      total of 6410 titles and abstracts and 225 full-text articles were reviewed. Of
      those selected for inclusion (n = 101), 15 articles described the elicitation of
      utility weights and 86 described economic modeling studies using utilities.
      Various methods were used to generate utilities, including time trade-off,
      contingent valuation, and willingness to pay, as well as a preference-based
      measure with associated value sets, such as the EuroQol five-dimensional
      questionnaire or the Health Utilities Index. In modeling studies, the source of
      utilities used was often unclear, poorly reported, or based on weak underlying
      evidence. We found no articles that reported on the elicitation or use of
      utilities in diphtheria, polio, or tetanus. CONCLUSIONS: The scarcity of
      appropriate utility weights for vaccine-preventable infectious diseases in
      children and a lack of standardization in their use in economic assessments limit
      the ability to accurately assess the benefits associated with interventions to
      prevent infectious diseases. This is an issue that should be of concern to those
      making decisions regarding the prevention and treatment of infectious childhood
      illnesses.

PMID- 27021762
TI  - Methods Used in Economic Evaluations of Tuberculin Skin Tests and Interferon
      Gamma Release Assays for the Screening of Latent Tuberculosis Infection: A
      Systematic Review.
AB  - BACKGROUND: Latent tuberculosis infection (LTBI) provides a constant pool of new
      active tuberculosis cases; a third of the earth's population is estimated to be
      infected with LTBI. OBJECTIVE: The objective of this systematic review was to
      assess the quality and summarize the available evidence from published economic
      evaluations reporting on the cost-effectiveness of tuberculin skin tests (TSTs)
      compared with interferon gamma release assays (IGRAs) for the screening of LTBI.
      METHODS: An extensive systematic review of the published literature was
      conducted. A two-step process was adopted to identify relevant articles:
      information was extracted into evidence tables and then analyzed. The quality of
      the publications was assessed using a 10-item checklist specific for economic
      evaluations. RESULTS: Twenty-eight studies were identified for inclusion in this
      review. Most of the studies found IGRAs to be more cost-effective than TSTs;
      however, the conclusions from the studies varied significantly. Most studies
      scored highly on the checklist although only one fulfilled all the stipulated
      criteria. A wide variety of methodological approaches were documented; identified
      differences included the type of economic evaluation and model, time horizon,
      perspective, and outcomes measures. CONCLUSIONS: The lack of consistent methods
      across studies makes it difficult to draw any firm conclusions about the most
      cost-effective option between TSTs and IGRAs. This problem can be solved by
      improving the quality of economic evaluation studies in the field of LTBI
      screening, through adherence to quality checklists.

PMID- 27021764
TI  - Systematic Review of Economic Evaluations of Units Dedicated to Acute Coronary
      Syndromes.
AB  - BACKGROUND: Dedicated units for the care of acute coronary syndrome (ACS) have
      been submitted to economic evaluations; however, the results have not been
      systematically presented. OBJECTIVE: To identify and summarize economic outcomes
      of studies on hospital units dedicated to the initial care of patients with
      suspected or confirmed ACS. METHODS: A systematic review of literature to
      identify economic evaluations of chest pain unit (CPU), coronary care unit (CCU),
      or equivalent units was done. Two search strategies were used: the first one to
      identify economic evaluations irrespective of study design, and the second one to
      identify randomized clinical trials that reported economic outcomes. The
      following databases were searched: MEDLINE, EMBASE, CENTRAL, and National Health
      Service (NHS)Economic Evaluation Database. Data extraction was performed by two
      independent reviewers. Costs were inflated to 2012 values. RESULTS: Search
      strategies retrieved five partial economic evaluations based on observational
      studies, six randomized clinical trials that reported economic outcomes, and five
      model-based economic evaluations. Overall, cost estimates based on observational
      studies and randomized clinical trials reported statistically significant cost
      savings of more than 50% with the adoption of CPU care instead of routine
      hospitalization or CCU care for suspected low-to-intermediate risk patients with
      ACS (median per-patient cost US $1,969.89; range US $1,002.12-13,799.15). Model
      based economic evaluations reported incremental cost-effectiveness ratios below
      US $ 50,000/quality-adjusted life-year for all comparisons between intermediate
      care unit, CPU, or CCU with routine hospital admissions. This finding was
      sensible to myocardial infarction probability. CONCLUSIONS: Published economic
      evaluations indicate that more intensive care is likely to be cost-effective in
      comparison to routine hospital admission for patients with suspected ACS.

PMID- 27021765
TI  - Erratum.

PMID- 27021763
TI  - Patient-Centered Outcomes of Medication Adherence Interventions: Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: Using meta-analytic procedures to synthesize changes in patient
      centered outcomes after medication adherence interventions. METHODS: Strategies
      to locate studies included online searches of 13 databases and 19 research
      registries, hand searches of 57 journals, and author and ancestry searches of all
      eligible studies. Search terms included patient compliance, medication adherence,
      and related terms. Searches were conducted for all studies published since 1960.
      Eligible published or unpublished primary studies tested medication adherence
      interventions and reported medication knowledge, quality of life, physical
      function, and symptom outcomes. Primary study attributes and outcome data were
      reliably coded. Overall standardized mean differences (SMDs) were analyzed using
      random-effects models. Dichotomous and continuous moderator analyses and funnel
      plots were used to explore risks of bias. RESULTS: Thorough searching located 141
      eligible reports. The reports included 176 eligible comparisons between treatment
      and control subjects across 23,318 subjects. Synthesis across all comparisons
      yielded statistically significant SMDs for medication knowledge (d = 0.449),
      quality of life (d = 0.127), physical function (d = 0.142), and symptoms (d =
      0.182). The overall SMDs for studies focusing on subsamples of patients with
      specific illnesses were more modest but also statistically significant. Of
      specific symptoms analyzed (depression, anxiety, pain, energy/vitality,
      cardiovascular, and respiratory), only anxiety failed to show a significant
      improvement after medication adherence interventions. Most SMDs were
      significantly heterogeneous, and risk of bias analyses suggested links between
      study quality and SMDs. CONCLUSIONS: Modest but significant improvements in
      patient-centered outcomes were observed after medication adherence interventions.

PMID- 27021767
TI  - Erratum to: Increased dietary levels of alpha-linolenic acid inhibit mammary
      tumor growth and metastasis.

PMID- 27021766
TI  - Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE
      mediated activation of human intestinal mast cells.
AB  - PURPOSE: Allergic diseases with mast cells (MC) as main effector cells show an
      increased prevalence. MC also play an essential role in other inflammatory
      conditions. Therapeutical use of anti-inflammatory nutraceuticals directly
      targeting MC activation could be of interest for afflicted patients. Nobiletin
      and tangeretin are citrus peel polymethoxyflavones, a group of citrus flavonoids,
      possessing anticancer, antimetastatic, and anti-inflammatory activities. Here, we
      analyzed the effects of nobiletin/tangeretin on LPS- and IgE-mediated stimulation
      of human intestinal mast cells (hiMC). METHODS: MC isolated from human intestinal
      tissue were treated with different concentrations of nobiletin or tangeretin
      prior to stimulation via LPS/sCD14 or IgE-dependently. Degranulation, pro
      inflammatory cytokine expression and phosphorylation of ERK1/2 were examined.
      RESULTS: Expression of CXCL8, CCL3, CCL4 and IL-1beta in response to LPS-mediated
      stimulation was inhibited by nobiletin/tangeretin. hiMC activated IgE-dependently
      showed a reduced release of beta-hexosaminidase and cysteinyl LTC4 in response to
      nobiletin, but not in response to tangeretin. Expression of CXCL8, CCL2, CCL3,
      CCL4 and TNF in IgE-dependently activated hiMC was decreased in a dose-dependent
      manner following treatment with nobiletin/tangeretin. IL-1beta expression was
      only reduced by tangeretin. Compared to treatment with NF-kappaB inhibitor
      BMS345541 or MEK-inhibitor PD98059, nobiletin and tangeretin showed similar
      effects on mediator production. Phosphorylation of ERK1/2 upon IgE-mediated
      antigen stimulation was significantly suppressed by nobiletin and tangeretin.
      CONCLUSIONS: Nobiletin and, to a lesser extent, tangeretin could be considered as
      anti-inflammatory nutraceuticals by reducing release and production of
      proinflammatory mediators in MC.

PMID- 27021768
TI  - What is the real cause of hepatic dysfunction after zinc phosphide containing
      rodenticide poisoning?

PMID- 27021769
TI  - Global transcriptome analyses provide evidence that chloroplast redox state
      contributes to intracellular as well as long-distance signalling in response to
      stress and acclimation in Arabidopsis.
AB  - Global transcriptome analyses were used to assess the interactive effects of
      short-term stress versus long-term acclimation to high light (HL), low
      temperature (LT) and excitation pressure in Arabidopsis. Microarray analyses
      indicated that exposure to stress resulted in two times as many modulated
      transcripts in both, high-light-treated and low-temperature-treated plants,
      compared to plants that were fully acclimated to either one of these conditions.
      We showed that 10.9 % of all transcripts were regulated in the same way by both
      stress conditions, and hence, were categorized as excitation pressure regulated,
      rather than regulated by either high-light or low-temperature stress per se. This
      group of chloroplast redox-sensitive genes included various photosynthetic genes
      as well as genes known to be associated with cold acclimation (cbf3, cor15A,
      cor15B) and gibberellic acid (GA) metabolism and signalling (ga2ox1, gai).
      Chemical inhibition of the photosynthetic electron transport by either DCMU or
      DBMIB indicated that although the plastoquinone pool contributes significantly to
      redox regulation of the transcriptome (8.6 %), it appears that PSI represents the
      major source of redox signals (89 %), whereas PSII appears to contribute only 3.1
      %. A comparison of the gene expression profiles between stress and acclimated
      plants indicated that 10 % of the genes induced by a short, 1-h stress were also
      associated with long-term acclimation to high excitation pressure. This included
      the APETALA2/ETHYLENE-RESPONSIVE-BINDING PROTEIN family, the MYB domain- and MYB
      related transcription factor family as well as the GRAS transcription factor
      family important in GA signalling confirming that acclimation to stress is a time
      nested phenomenon. We suggest that acclimation to photosynthetic redox imbalance
      extends beyond the chloroplast and the leaf cell to systemic ROS signalling. This
      is discussed in terms of the control of plant phenotype through regulation of the
      nuclear encoded cbf regulon and GA metabolism. 

PMID- 27021770
TI  - A Practical Approach to Autonomic Dysfunction in Patients with Headache.
AB  - The presence of autonomic symptoms can make the diagnosis of headache
      challenging. While commonly seen with the trigeminal autonomic cephalalgias,
      autonomic dysfunction can also be present in patients with migraine, or with a
      variety of secondary headaches. The pathophysiology of cranial autonomic symptoms
      in headache is based between the trigeminal system and the hypothalamus. This
      article will review the pathophysiology and presence of autonomic dysfunction in
      headache and will provide techniques to help in headache diagnosis in patients
      with autonomic dysfunction.

PMID- 27021771
TI  - History, Evolution, and Importance of Emergency Endovascular Treatment of Acute
      Ischemic Stroke.
AB  - More than 800,000 people in North America suffer a stroke each year, with
      ischemic stroke making up the majority of these cases. The outcomes of ischemic
      stroke range from complete functional and cognitive recovery to severe disability
      and death; outcome is strongly associated with timely reperfusion treatment.
      Historically, ischemic stroke has been treated with intravenous thrombolytic
      agents with moderate success. However, five recently published positive trials
      have established the efficacy of endovascular treatment in acute ischemic stroke.
      In this review, we will discuss the history of stroke treatments moving from
      various intravenous thrombolytic drugs to intra-arterial thrombolysis, early
      mechanical thrombectomy devices, and finally modern endovascular devices. Early
      endovascular therapy failures, recent successes, and implications for current
      ischemic stroke management and future research directions are discussed. 

PMID- 27021772
TI  - Medulloblastoma: Tumor Biology and Relevance to Treatment and Prognosis Paradigm.
AB  - Medulloblastoma is a malignant embryonic brain tumor arising in the posterior
      fossa and typically occurring in pediatric patients. Current multimodal treatment
      regimes have significantly improved the survival rates; however, a marked
      heterogeneity in therapy response is observed, and one third of all patients die
      within 5 years after diagnosis. Large-scale genetic and transcriptome analysis
      revealed four medulloblastoma subgroups (WNT, SHH, Group 3, and Group 4)
      associated with different demographic parameters, tumor manifestation, and
      clinical behavior. Future treatment protocols will integrate molecular
      classification schemes to evaluate subgroup-specific intensification or de
      escalation of adjuvant therapies aimed to increase tumor control and reduce
      iatrogenic induced morbidity. Furthermore, the identification of genetic drivers
      allows assessing target therapies in order to increase the chemotherapeutic
      armamentarium. This review highlights the biology behind the current
      classification system and elucidates relevant aspects of the disease influencing
      forthcoming clinical trials.

PMID- 27021774
TI  - The Clinical Approach to Encephalitis.
AB  - Encephalitis has various etiologies, but viral infections and autoimmune
      disorders are the most commonly identified. Clinical signs, geographical clues,
      and diagnostic testing-including cerebrospinal fluid abnormalities and magnetic
      resonance imaging abnormalities-can be helpful in identifying the cause. Certain
      forms of encephalitis have specific treatments; hence, establishing a diagnosis
      rapidly and accurately is crucial. Here, we describe the clinical approach to
      diagnosing several common etiologies of encephalitis as well as treatment
      strategies. 

PMID- 27021776
TI  - Health workforce development in the European Union: A matrix for comparing
      trajectories of change in the professions.
AB  - This article assesses professional development trajectories in top-, middle- and
      basic-level health workforce groups (doctors, nurses, care assistants) in
      different European Union countries using available international databases. Three
      theoretical strands (labour market, welfare state, and professions studies) were
      connected to explore ideal types and to develop a matrix for comparison. With a
      focus on larger EU-15 countries and four different types of healthcare systems,
      Germany, Italy, Sweden and the United Kingdom serve as empirical test cases. The
      analysis draws on selected indicators from public statistics/OECD data and micro
      data from the EU Labour Force Survey. Five ideal typical trajectories of
      professional development were identified from the literature, which served as a
      matrix to compare developments in the three health workforce groups. The results
      reveal country-specific trajectories with uneven professional development and
      bring opportunities for policy interventions into view. First, there is a need
      for integrated health labour market monitoring systems to improve data on the
      skills mix of the health workforce. Second, a relevant number of health workers
      with fixed contracts and involuntary part-time reveals an important source for
      better recruitment and retention strategies. Third, a general trend towards
      increasing numbers while worsening working conditions was identified across our
      country cases. This trend hits care assistants, partly also nurses, the most. The
      research illustrates how public data sources may serve to create new knowledge
      and promote more sustainable health workforce policy. 

PMID- 27021775
TI  - Chronic Traumatic Encephalopathy and Movement Disorders: Update.
AB  - Association of repetitive brain trauma with progressive neurological
      deterioration has been described since the 1920s. Punch drunk syndrome and
      dementia pugilistica (DP) were introduced first to explain symptoms in boxers,
      and more recently, chronic traumatic encephalopathy (CTE) has been used to
      describe a neurodegenerative disease in athletes and military personal with a
      history of multiple concussions. Although there are many similarities between DP
      and CTE, a number of key differences are apparent especially when comparing
      movement impairments. The aim of this review is to compare clinical and
      pathological aspects of DP and CTE with a focus on disorders of movement. 

PMID- 27021777
TI  - Presenting Baseline Coagulation of Infra Renal Ruptured Abdominal Aortic
      Aneurysm: A Systematic Review and Pooled Analysis.
AB  - BACKGROUND: The incidence of coagulopathy in patients presenting with rAAA is not
      clear. The lack of high-quality evidence has led to various speculations,
      reliance on anecdotal experience, and suggestions about their appropriate
      haemostatic resuscitation. The aim of this systematic review is to establish the
      baseline coagulation status of infra renal ruptured abdominal aortic aneurysms
      (rAAA) against defined standards and definitions. METHODS: An electronic search
      of literature in Medline, CINHAL, Scopus Embase, and Cochrane library was
      performed in accordance with the PRISMA guidelines. Quality assessment of
      articles was performed using the Oxford critical appraisal skills programme
      (CASP) and their recommendation for practice was examined through National
      Institute for Health and Care Excellence (NICE). Information on platelet count,
      international normalisation ratio (INR), activated partial prothrombin time
      (aPTT), prothrombin time (PT) fibrinogen and D-dimer was extracted, and pooled
      analysis was performed in accordance with the definition of coagulopathy and its
      subtypes. Pooled prevalence of coagulopathies and 95% CI were estimated with a
      variance weighted random effects model. RESULTS: Seven studies, comprising 461
      patients were included in this systematic review. Overall weighted prevalence of
      coagulopathy was 12.3% (95% CI 10.7-13.9), 11.7% for INR (95% CI 1-31.6), 10.1%
      for platelet count (95% CI 1-26.8), and 11.1% for aPTT (95% CI 0.78-31).
      Fibrinogen serum concentration level was normal in 97%, and 46.2% (n = 55) of
      patients had elevated D-dimer. Only 6% of the entire population demonstrated
      significant coagulopathy. DIC was noted in 2.4% of the population. CONCLUSION:
      This first systematic review of literature on baseline coagulation of rAAAs
      suggests that the majority of these patients do not present with coagulopathy and
      only a minor proportion of patients present with significant coagulopathy.

PMID- 27021778
TI  - Portuguese family with the co-occurrence of frontotemporal lobar degeneration and
      neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation.
AB  - We and others have reported heterozygous progranulin mutations as an important
      cause of frontotemporal lobar degeneration (FTLD). It has been identified a
      complete progranulin deficiency because of a homozygous mutation in a sibling
      pair with neuronal ceroid lipofuscinosis (NCL). Here, we describe the first case
      of NCL caused by a homozygous progranulin mutation segregating in a family with
      neuropathological confirmed FTLD. In this FTLD-NCL family, we detail the clinical
      phenotype, neuropsychological evaluation and imaging data of our proband
      harboring a homozygous mutation, c.900_901dupGT, with serum progranulin level (<6
      ng/mL). Symptoms included rapidly progressive visual deficit, slightly
      dysarthria, and cerebellar ataxia. The electroretinogram confirmed a severe
      attenuation of rod and cone responses compatible with retinal dystrophy diagnosis
      and magnetic resonance imaging showed severe global cerebellar atrophy. In
      contrast, heterozygous relatives presented behavioral variant of frontotemporal
      dementia (FTD) and some also developed extrapyramidal features compatible with
      corticobasal syndrome. Our findings suggest the importance of assessing serum
      progranulin levels in suspected recessive adult-onset NCL cases. Overall, a more
      holistic neurologic intervention is needed to guarantee a proper genetic
      counseling in cases like the present family where two distinct phenotypes are
      generated according to the individuals' mutation state. 

PMID- 27021779
TI  - PETS-D (parents education through simulation-diabetes): Parents' qualitative
      results.
AB  - OBJECTIVE: Parents who have a child newly diagnosed with type 1 diabetes (T1D)
      must quickly learn daily diabetes self-management. An RCT was conducted using
      human patient simulation (HPS) to enhance parents learning diabetes self
      management with children with new-onset T1D. The purpose of this study was to
      describe parents' perspectives of using HPS to augment diabetes education.
      METHODS: A qualitative descriptive design was used with open-ended in-depth
      interviews of parents (n=49) post-intervention. Qualitative directed content
      analysis was used. RESULTS: The majority of parents were positive about learning
      with HPS. Although a few parents said the HPS was "hokey" or "creepy," most
      reported the visual and hands-on learning was realistic and very beneficial.
      Seeing a seizure increased their fear although they would have panicked if they
      had not had that learning experience, and it helped build their diabetes self
      management confidence. Recommendations included teaching others with the HPS
      (grandparents, siblings, babysitters, and school nurses). CONCLUSION: HPS
      enhanced education is an acceptable and viable option that was generally well
      received by parents of children with new-onset T1D. PRACTICE IMPLICATIONS: The
      technique should be studied with parents of children with other chronic illnesses
      to see if the benefits found in this study are applicable to other settings.

PMID- 27021780
TI  - Exploring the utility of the vignette technique in promoting advance care
      planning discussions with cancer patients and caregivers.
AB  - OBJECTIVE: We aimed to specifically examine patients' and caregivers'
      perspectives about the use of the vignette technique (VT) integrating clinical
      scenarios, as a potential tool for facilitating advance care planning (ACP)
      discussions. METHODS: Secondary analysis of data from three studies that
      incorporated the VT, focusing on statements specific to use of the VT and using a
      qualitative descriptive design informed by grounded theory. RESULTS: Data from 85
      participants were analyzed. Participants varied in their personal identification
      with scenarios, with caregivers being more accurate. Scenarios prompted
      consideration and participation in ACP discussions, sometimes steering
      conversations in directions that participants were ready to consider. However,
      scenarios also risked evoking distress in participants who may have chosen to
      avoid discussions. CONCLUSIONS: For some patients, scenarios of possible clinical
      outcomes may provide a neutral platform to promote ACP conversations in a non
      threatening manner and allow for exploration of ACP domains to greater depth.
      PRACTICE IMPLICATIONS: Vignettes may be used in staff training through role-play
      or case discussions; as part of face-to-face interventions to improve knowledge
      and information processing and to facilitate the initiation of sensitive
      conversations. Its use in audio-visual formats may further enhance end-of-life
      dialogue and warrants further consideration.

PMID- 27021782
TI  - Cu-catalyzed C-H amination/Ullmann N-arylation domino reaction: a straightforward
      synthesis of 9,14-diaryl-9,14-dihydrodibenzo[a,c]phenazine.
AB  - A Cu-catalyzed C-H amination/Ullmann N-arylation domino reaction of phenanthrene
      9,10-diamines with aryl iodides has been developed, which provides a
      straightforward and facile access to 9,14-diaryl-9,14
      dihydrodibenzo[a,c]phenazine. This reaction features readily available starting
      materials and simple experimental operation. 

PMID- 27021773
TI  - Mapping the Connectome Following Traumatic Brain Injury.
AB  - There is a paucity of accurate and reliable biomarkers to detect traumatic brain
      injury, grade its severity, and model post-traumatic brain injury (TBI) recovery.
      This gap could be addressed via advances in brain mapping which define injury
      signatures and enable tracking of post-injury trajectories at the individual
      level. Mapping of molecular and anatomical changes and of modifications in
      functional activation supports the conceptual paradigm of TBI as a disorder of
      large-scale neural connectivity. Imaging approaches with particular relevance are
      magnetic resonance techniques (diffusion weighted imaging, diffusion tensor
      imaging, susceptibility weighted imaging, magnetic resonance spectroscopy,
      functional magnetic resonance imaging, and positron emission tomographic methods
      including molecular neuroimaging). Inferences from mapping represent unique
      endophenotypes which have the potential to transform classification and treatment
      of patients with TBI. Limitations of these methods, as well as future research
      directions, are highlighted. 

PMID- 27021781
TI  - Testing with feedback improves recall of information in informed consent: A proof
      of concept study.
AB  - OBJECTIVE: This study investigates whether applying educational testing
      approaches to an informed consent video for a medical procedure can lead to
      greater recall of the information presented. METHODS: Undergraduate students
      (n=120) were randomly assigned to watch a 20-min video on informed consent under
      one of three conditions: 1) tested using multiple-choice knowledge questions and
      provided with feedback on their answers after each 5-min segment; 2) tested with
      multiple choice knowledge questions but not provided feedback after each segment;
      or 3) watched the video without knowledge testing. RESULTS: Participants who were
      tested and provided feedback had significantly greater information recall
      compared to those who were tested but not provided feedback and to those not
      tested. The effect of condition was stronger for moderately difficult questions
      versus easy questions. CONCLUSIONS: Inserting knowledge tests and providing
      feedback about the responses at timed intervals in videos can be effective in
      improving recall of information. PRACTICAL IMPLICATION: Providing informed
      consent information through a video not only standardizes the material, but using
      testing with feedback inserted within the video has the potential to increase
      recall and retention of this material.

PMID- 27021783
TI  - Coding accuracy on the psychophysical scale.
AB  - Sensory neurons are often reported to adjust their coding accuracy to the
      stimulus statistics. The observed match is not always perfect and the maximal
      accuracy does not align with the most frequent stimuli. As an alternative to a
      physiological explanation we show that the match critically depends on the chosen
      stimulus measurement scale. More generally, we argue that if we measure the
      stimulus intensity on the scale which is proportional to the perception
      intensity, an improved adjustment in the coding accuracy is revealed. The unique
      feature of stimulus units based on the psychophysical scale is that the coding
      accuracy can be meaningfully compared for different stimuli intensities, unlike
      in the standard case of a metric scale. 

PMID- 27021784
TI  - Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative
      stress and inflammation induced by ultraviolet B irradiation.
AB  - Skin exposure to ultraviolet B (UVB) irradiation has increased significantly in
      recent years due to ozone depletion, and it represents the main cause of many
      skin diseases. Hesperidin methyl chalcone (HMC) is a compound used to treat
      vascular diseases that has demonstrated anti-inflammatory activities in pre
      clinical studies. Herein, we tested the antioxidant activity of HMC in cell free
      systems and the in vivo effects of a stable topical formulation containing HMC in
      a mouse model of skin oxidative stress and inflammation induced by UVB
      irradiation. HMC presented ferric reducing power, neutralized 2,2'-azino-bis (3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl free radicals, and
      inhibited lipid peroxidation. In hairless mice, a topical formulation containing
      HMC inhibited UVB irradiation-induced skin edema, depletion of antioxidant
      capacity (ferric and ABTS reducing abilities and catalase activity), lipid
      peroxidation, superoxide anion production and mRNA expression of gp91phox
      (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase 2 sub-unity). In
      addition, HMC inhibited UVB irradiation-induced depletion of reduced glutathione
      levels by maintaining glutathione peroxidase-1 and glutathione reductase mRNA
      expression, prevented down-regulation of nuclear factor erythroid 2-related
      factor 2 (Nrf2) mRNA expression and increased heme oxygenase-1 mRNA expression.
      Finally, we demonstrated that topical application of the formulation containing
      HMC inhibited cytokine (TNF-alpha, IL-1beta, IL-6, and IL-10) production induced
      by UVB irradiation. Therefore, this topical formulation containing HMC is a
      promising new therapeutic approach to protecting the skin from the deleterious
      effects of UVB irradiation. 

PMID- 27021785
TI  - Does fish oil or folic acid prevent vascular changes in female progeny caused by
      maternal exposure to fluoxetine?
AB  - AIMS: Fluoxetine (FLX) is an antidepressant worldwide prescribed throughout life
      stages, including pregnancy and breastfeeding. Out of pregnancy, the combination
      of FLX with fish oil (FO) and folic acid (FA) is carried to enhance the
      therapeutic activity and reduce the side effects of the antidepressant. During
      pregnancy, FO and FA have been used to promote fetal development, and reduce, in
      mother, the risk of gestational and post-pregnancy depression. To evaluate if
      maternal exposure during pregnancy and lactation to FLX associated with FO or FA
      would prevent the antidepressant side effects in aorta reactivity and nitric
      oxide metabolites (NOx) plasmatic levels. We also sought to understand, in female
      offspring, the vascular effects of intrauterine and lactation exposure to FO and
      FA monotherapy. MAIN METHODS: Wistar rats were treated with water (control
      group), FLX (5mg/kg/day), FO (1.3g/kg/day), FA (3mg/kg/day), FLX+FO and FLX+FA,
      throughout pregnancy and lactation. On adulthood, in female offspring were
      evaluated the vascular reactivity to phenylephrine (Phe), the NOx and
      homocysteine (HCY) plasmatic levels. KEY FINDINGS: The developmental exposure to
      the associations of FO or FA with FLX did not correct the aortic hyporreactivity
      and increased NOx levels induced by intrauterine and lactation exposure to FLX.
      Also, isolated exposure to FO and FA did not interfere with Phe-induced aortic
      contraction and neither interferes with NOx and HCY plasmatic levels.
      SIGNIFICANCE: The developmental exposure to FO and FA was safe for vascular
      function of female offspring but did not prevent the vascular effects of FLX
      exposure.

PMID- 27021786
TI  - Unraveling the role of high-intensity resistance training on left ventricle
      proteome: Is there a shift towards maladaptation?
AB  - High-intensity resistance training (RT) induces adaptations that improve
      physiological function. However, high intensity, volume and/or frequency may lead
      to injury and other health issues such as adverse cardiac effects. The aim of
      this study was to evaluate the effect of RT on left ventricle proteome, and to
      identify the pathways involved on the harmful adaptations induced by this
      protocol. Male Wistar rats were randomized into 2 groups: Trained (T) and
      Sedentary (S). Animals from T group were trained for 6weeks, and then all the
      animals were sacrificed and left ventricle was isolated for analysis. We
      identified 955 proteins, and 93 proteins were considered; 36 were expressed
      exclusively in T group, and 4 in S group. Based on quantitative analysis, 42
      proteins were found overexpressed and 11 underexpressed in T group compared with
      S group. Using the Gene Ontology to relate the biological processes in which
      these proteins are involved, we conclude that RT protocol promotes changes
      similar to those found in the initial phase of heart failure, but we also
      observed a concomitant increased expression of protective proteins, suggesting
      the activation of pathways to avoid major damages on left ventricle and delay the
      onset of pathological hypertrophy. STATEMENT OF SIGNIFICANCE OF THE STUDY: Our
      study shows that high-intensity RT protocol changes left ventricle proteome,
      modifying metabolic profile of heart tissue and inducing the expression of
      proteins that acts against cardiac injury. We hypothesize that these adaptations
      occur to prevent the onset of cardiac dysfunction. Despite highly significant, it
      remains to be determined whether these adaptations are sufficient to further keep
      left ventricle function and exert cardioprotection, and whether this panel will
      be shifted towards maladaptation, and heart failure.

PMID- 27021787
TI  - Antagonists to endothelin receptor type B promote apoptosis in human pulmonary
      arterial smooth muscle cells.
AB  - AIMS: Vascular remodeling results from aberrations in the balance between cell
      proliferation and death, which is seen in the obstructive vasculature of
      pulmonary arterial hypertension (PAH). Endothelin (ET)-1 has a potent
      proliferative activity on vascular smooth muscle cells, and ET receptor
      inhibitors are used to treat PAH; however, it remains unclear whether ET receptor
      inhibition contributes to the apoptosis of pulmonary arterial smooth muscle cells
      (PASMCs), another cause of pulmonary vascular remodeling. MAIN METHODS: Cultured
      human PASMCs were treated with the ETA receptor antagonist BQ-123 (100MUM), or
      the ETB antagonist A-192621 (1-100MUM) or BQ-788 (1-100MUM) for 48h. The cells
      were then incubated for another 24h with or without doxorubicin (DOX, 1MUM), an
      anthracyclin antitumor antibiotic that promotes p53-mediated apoptosis. Cell
      viability and apoptosis were evaluated by MTT assays, caspase-3/7 activity
      assays, and Western blots for cleaved caspase-3 expression. KEY FINDINGS: The
      viability of PASMCs was significantly decreased by A-192621 and BQ-788, in a dose
      dependent manner. A-192621 and BQ-788 significantly increased the caspase-3/7
      activity and cleaved caspase-3 expression in PASMCs. The PASMCs' susceptibility
      to DOX-induced apoptosis was significantly higher in the presence of A-192621 and
      BQ-788 than with vehicle. However, BQ-123 did not affect these parameters.
      SIGNIFICANCE: Blockade of the ETB receptor increases the extent of apoptosis and
      susceptibility to DOX-induced apoptosis in PASMCs. Apoptosis caused by ETB
      receptor blockade in PASMCs may be one of the mechanisms by which vascular
      remodeling is reduced in ET receptor inhibitor-based PAH treatments.

PMID- 27021788
TI  - Seasonality of suicide behavior in Northwest Alaska: 1990-2009.
AB  - OBJECTIVES: Suicide is a leading cause of death worldwide, and disproportionately
      affects Indigenous populations. Seasonal suicide patterns are variable in the
      literature, and could offer novel approaches to the timing and focus of
      prevention efforts if better understood. With a suicide surveillance system in
      place since 1989, this study offers an unprecedented opportunity to explore
      seasonal variations in both fatal and non-fatal suicide behavior in an Indigenous
      Arctic region. STUDY DESIGN: Cross-sectional. METHODS: In this descriptive study,
      we analyzed data collected from 1990 to 2009 in the rural northwest region of
      Alaska, both graphically and using the chi-squared test for multinomials.
      RESULTS: We found a significant monthly variation for suicide attempts, with a
      peak in suicide behavior observed between April and August (P = 0.0002). Monthly
      variation was more pronounced among individuals <=29 years of age, and was
      present in both males and females, although the seasonal pattern differed by sex.
      CONCLUSIONS: Our findings of a significant seasonal pattern in suicide behavior,
      with monthly variation (summer peak) in non-fatal suicide behavior among younger
      age groups, and among both males and females can assist planners in targeting
      subpopulations for prevention at different times of the year.

PMID- 27021789
TI  - Effects of a workplace travel plan intervention encouraging active travel to
      work: outcomes from a three-year time-series study.
AB  - OBJECTIVE: To evaluate the effects of a three-year workplace travel plan
      intervention on increasing active travel to work. STUDY DESIGN: A time-series
      study with staff was conducted in 2011 (n = 804), 2012 (n = 904), 2013 (n = 872)
      and 2014 (n = 687). METHODS: A travel plan was implemented at a large, outer
      suburban worksite in Sydney, Australia. Implementation was assessed by reviewing
      annual reports including travel plan actions and their status. Annual cross
      sectional on-line surveys assessed primary outcomes which included change in the
      proportion of staff travelling to work via active modes. Multivariate logistic
      regression was used to adjust for confounders. RESULTS: Strategies to encourage
      active travel were partially implemented. An average survey response rate was 23%
      (n = 817). The proportion of staff travelling actively to work increased by 4%-6%
      across intervention years compared to the baseline, and this increase was
      significant in 2012 (P = 0.04) and 2013 (P = 0.003). Compared to baseline, after
      adjusting for distances staff lived from work staff had 33% (95% CI 1%-74%)
      greater odds of travelling to work via active modes in 2012, and 50% (95% CI 15%
      96%) greater odds in 2013. There was no evidence of change in physical activity
      levels. CONCLUSIONS: A workplace travel plan which only included strategies to
      encourage active travel to work achieved small but significant increases in
      active travel. Workplace travel plans appear to be a promising way to increase
      active travel to work.

PMID- 27021790
TI  - Nondogmatism.
AB  - The following is based on my remarks on receipt of the 2015 ACE award for
      outstanding contributions to epidemiology.

PMID- 27021791
TI  - Translatability: what does it mean in drug discovery?

PMID- 27021792
TI  - Molecular basis for cytokine biomarkers of complex 3D microtissue physiology in
      vitro.
AB  - 'Physiologically more-relevant' claims are readily made for cells cultured on any
      surface or in a scaffold that provides loosely defined 3D geometry. A set of
      tools to measure culture '3D-ness' more accurately are needed. Such tools should
      find applications in fields ranging from high-throughput identification of
      substrates for tissue engineering and regenerative medicine to cell-based
      screening of drug candidates. Until now, these fields have not provided a
      consensus for the most promising place to initiate the search. Here, we review
      recent advances in transcriptomic, proteomic, inflammation and oncology-related
      pathways, as well as functional studies that strongly point to cytokines as the
      most likely compounds to form the missing consensus.

PMID- 27021794
TI  - Nonmonotonic response of drop impacting on liquid film: mechanism and scaling.
AB  - Drop impacting on a liquid film with a finite thickness is omnipresent in nature
      and plays a critical role in numerous industrial processes. The impact can result
      in either bouncing or merging, which is mainly controlled by the impact inertia
      of the drop and film thickness. Although it is known that impact with inertia
      beyond a critical value on a thick film promotes merging through the breakage of
      the interfacial gas layer, here we demonstrate that for an impact inertia less
      than that critical value, increasing the film thickness leads to a nonmonotonic
      transition from merging to bouncing to merging and finally to bouncing again. For
      the first time, two different merging mechanisms are identified and the scaling
      laws of the nonmonotonic transitions are developed. These results provide
      important insights into the role of the film thickness in the impact dynamics,
      which is critical for optimizing operating conditions for spray or ink-jet
      systems among others.

PMID- 27021795
TI  - Re: Laura Evangelista, Alberto Briganti, Stefano Fanti, et al. New Clinical
      Indications for 18F/11C-choline, New Tracers for Positron Emission Tomography and
      a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the
      Literature. Eur Urol 2016;70:161-75.

PMID- 27021793
TI  - Genome of Leptomonas pyrrhocoris: a high-quality reference for monoxenous
      trypanosomatids and new insights into evolution of Leishmania.
AB  - Many high-quality genomes are available for dixenous (two hosts) trypanosomatid
      species of the genera Trypanosoma, Leishmania, and Phytomonas, but only
      fragmentary information is available for monoxenous (single-host)
      trypanosomatids. In trypanosomatids, monoxeny is ancestral to dixeny, thus it is
      anticipated that the genome sequences of the key monoxenous parasites will be
      instrumental for both understanding the origin of parasitism and the evolution of
      dixeny. Here, we present a high-quality genome for Leptomonas pyrrhocoris, which
      is closely related to the dixenous genus Leishmania. The L. pyrrhocoris genome
      (30.4 Mbp in 60 scaffolds) encodes 10,148 genes. Using the L. pyrrhocoris genome,
      we pinpointed genes gained in Leishmania. Among those genes, 20 genes with
      unknown function had expression patterns in the Leishmania mexicana life cycle
      suggesting their involvement in virulence. By combining differential expression
      data for L. mexicana, L. major and Leptomonas seymouri, we have identified
      several additional proteins potentially involved in virulence, including SpoU
      methylase and U3 small nucleolar ribonucleoprotein IMP3. The population genetics
      of L. pyrrhocoris was also addressed by sequencing thirteen strains of different
      geographic origin, allowing the identification of 1,318 genes under positive
      selection. This set of genes was significantly enriched in components of the
      cytoskeleton and the flagellum.

PMID- 27021796
TI  - Oncologic Surveillance for Renal Cell Carcinoma: What Is Still Needed?

PMID- 27021798
TI  - Pressure ulcers in four Indonesian hospitals: prevalence, patient
      characteristics, ulcer characteristics, prevention and treatment.
AB  - The objective of this article was to study characteristics of pressure ulcer
      patients and their ulcers, pressure ulcer preventive and treatment measures in
      four Indonesian general hospitals. A multicentre cross-sectional design was
      applied to assess pressure ulcers and pressure ulcer care in adult patients in
      medical, surgical, specialised and intensive care units. Ninety-one of the 1132
      patients had a total of 142 ulcers. Half (44.0%) already had pressure ulcers
      before admission. The overall prevalence of category I-IV pressure ulcers was
      8.0% (95% CI 6.4-9.6), and the overall nosocomial pressure ulcer prevalence was
      4.5% (95% CI 3.3-5.7). Most pressure ulcer patients had friction and shear
      problems, were bedfast, had diabetes and had more bedridden days. Most ulcers
      (42.3%) were category III and IV. One third of the patients had both pressure
      ulcers and moisture lesions (36.3%) and suffered from pain (45.1%). The most
      frequently used prevention measures were repositioning (61.5%), skin moisturising
      (47.3%), patient education (36.3%) and massage (35.2%). Most pressure ulcer
      dressings involved saline-impregnated or antimicrobial gauzes. This study shows
      the complexities of pressure ulcers in Indonesian general hospitals and reveals
      that the quality of pressure ulcer care (prevention and treatment) could be
      improved by implementing the recent evidence-based international guideline.

PMID- 27021797
TI  - End-Stage Renal Disease After Renal Surgery in Patients with Normal Preoperative
      Kidney Function: Balancing Surgical Strategy and Individual Disorders at
      Baseline.
AB  - : Although nephron-sparing surgery (NSS) has demonstrated benefit in terms of
      renal function preservation, it is unclear whether NSS might also decrease the
      risk of end-stage renal disease (ESRD) relative to radical nephrectomy (RN). In
      the current paper, we aimed to report the rate and the predictors of ESRD after
      surgery, accounting for detailed individual baseline characteristics and
      comorbidities. A multi-institutional collaboration among five European tertiary
      care centers allowed study of 2027 patients with normal preoperative renal
      function and a clinically localized T1abN0M0 renal mass. Cox regression analyses
      were used to predict the risk of ESRD (defined as the onset of a postoperative
      estimated glomerular filtration rate <15ml/min per 1.73 m2) after adjusting for
      the individual baseline risk of developing chronic kidney disease. Univariable
      ESRD rates at 5 and 10 yr of follow-up were virtually equivalent for patients who
      underwent NSS (1.5% and 2.5%, respectively) versus RN (1.9% and 2.7%,
      respectively; hazard ratio [HR]: 0.8; 95% confidence interval [CI], 0.4-1.6).
      However, diabetes, smoking, uncontrolled hypertension, and other comorbidities
      were consistently more frequent in the NSS group relative to their RN
      counterparts. After adjusting for detailed baseline individual characteristics,
      NSS was shown to have an independent protective effect relative to RN (HR: 0.4;
      95% CI, 0.2-0.8; p=0.02) at multivariable analyses. PATIENT SUMMARY: After
      accounting for individual baseline characteristics, such as age, diabetes,
      uncontrolled hypertension, or other comorbidities, partial nephrectomy
      independently protects against end-stage renal disease and the consequent need
      for dialysis relative to radical nephrectomy.

PMID- 27021799
TI  - Use of optical coherence tomography and ultrasound biomicroscopy in the diagnosis
      of iridociliary cysts.

PMID- 27021800
TI  - The effect of the acceleration/deceleration trauma in angioid streaks: A
      pathogenic hypothesis.
AB  - CASE REPORT: A 59-year-old male with acceleration/deceleration cranial trauma
      (ADT), caused by a car accident. After one month, he presented with loss of
      visual acuity in the right eye. A fluorescein angiography test was performed and
      it detected centrifugal hyperfluorescent lines from the optic nerve head, a
      characteristic compatible with the diagnosis of angioid streaks. The loss of
      visual acuity was demonstrated by the discovery of a juxtafoveal choroidal
      neovascular membrane (CNV). CONCLUSION: ADT can cause hyper-extension of the
      eyeball in its equator line, producing the rupture of fragile structures such as
      the Bruch membrane (MB) in patients with angioid streaks and the subsequent
      formation of CNV.

PMID- 27021801
TI  - Molecular diagnosis in patients with retinoblastoma: Report of a series of cases.
AB  - OBJECTIVES: To report the benefits of genetic diagnosis in patients with
      retinoblastoma. METHOD: Observational study. Patients with retinoblastoma and
      their families were included. Demographic and clinical data were recorded. Blood
      and tumour samples were obtained. Next generation sequencing was performed on the
      samples. When deletion 13 q syndrome was suspected, cytogenetics microarray was
      performed (Cytoscan(r) HD, Affymetrix, Santa Clara, CA, USA), with a high density
      chip of 1.9 million of non-polymorphic probes and 750 thousand SNP probes.
      RESULTS: Of the 7 cases were analysed 4 were male. The mean age at diagnosis was
      21 months (range 5-36). Three cases had bilateral retinoblastoma, and 4
      unilateral. None had family history. In all patients, blood was analysed, and a
      study was performed on the tissue from 2 unilateral enucleated tumours, in which
      6 mutations were identified, all de novo. Just one was novel (c.164delC; case 1).
      One case of unilateral tumour revealed blood mosaicism, showing that his
      condition was inheritable, and that there is a high risk of developing
      retinoblastoma in the unaffected eye. The patient also has an increased risk of
      presenting with other primary tumours. CONCLUSION: Molecular diagnosis of RB1 in
      patients with retinoblastoma impacts on the decision process, costs, treatment,
      and prognosis of patients, as well as their families.

PMID- 27021804
TI  - Urinary straining contributes to inguinal hernia after radical retropubic
      prostatectomy.
AB  - OBJECTIVES: To verify whether abdominal pressure during urination represents an
      important factor in the postoperative development of inguinal hernia after
      radical retropubic prostatectomy. METHODS: Participants comprised 228 patients
      who underwent radical retropubic prostatectomy without prophylaxis for inguinal
      herniation between 2002 and 2007. Development of inguinal hernia was assessed
      from clinical records. Straining was rated on a six-point scale (straining score)
      according to frequency of straining using answers to question 6 of the
      International Prostate Symptom Score questionnaire preoperatively, and at 1, 3,
      6, 12, 18, 24 and 36 months after prostatectomy. Straining scores were compared
      between patients with and without postoperative inguinal hernia. Multivariate
      analysis was carried out to identify parameters associated with inguinal hernia
      development after prostatectomy. Associations between inguinal hernia development
      and frequency of postoperative urinary straining were also estimated. RESULTS:
      Straining score in both groups was significantly increased at 1 month after
      radical retropubic prostatectomy. This increase was significantly greater in the
      postoperative inguinal hernia group (P < 0.05). Throughout the observation
      period, postoperative straining scores were higher in the group with
      postoperative inguinal hernia than in the group without. On multivariate
      analysis, postoperative urinary straining and previous hernia repair represented
      significant risk factors for postoperative inguinal hernia. The proportion of
      patients without inguinal hernia decreased significantly with increasing
      frequency of postoperative urinary straining. CONCLUSION: Urinary straining is
      associated with inguinal hernia development after radical retropubic
      prostatectomy.

PMID- 27021805
TI  - Day-to-day pain symptoms are only weakly associated with opioid craving among
      patients with chronic pain prescribed opioid therapy.
AB  - BACKGROUND: Over the past decade, there has been a substantial rise in the use of
      opioids for the treatment of chronic noncancer pain. Despite the potential
      benefits of opioid therapy, the rise in the use of opioids has been accompanied
      by escalating rates of prescription opioid misuse and addiction. There is now a
      growing body of evidence indicating that opioid craving (i.e., the subjective
      desire to consume opioids) is one of the strongest determinants of opioid misuse
      among patients with chronic pain prescribed opioids. Although research has
      elucidated some of the factors associated with opioid craving, the contribution
      of patients' levels of pain to opioid craving remains unclear. OBJECTIVE: The
      main objective of this study was to examine the day-to-day association between
      pain and opioid craving. METHODS: In this longitudinal cohort study, patients
      with chronic pain prescribed opioid therapy completed baseline measures and were
      then asked to provide daily reports of pain intensity and opioid craving for a
      period of 14 days. RESULTS: Multilevel analyses indicated that day-to-day
      elevations in patients' levels of pain were associated with heightened opioid
      craving. That is, on more painful days, patients reported higher levels of
      craving. Within-person changes in pain intensity, however, explained less than 5%
      of the variance in patients' reports of craving. CONCLUSION: Findings from this
      study suggest that patients with chronic pain do not crave their opioid
      medications simply because they experience high levels of pain. The theoretical
      and clinical implications of our findings are discussed.

PMID- 27021806
TI  - Years of potential life lost amongst heroin users in the Australian Treatment
      Outcome Study cohort, 2001-2015.
AB  - BACKGROUND: Heroin use carries the highest burden of disease of any drug of
      dependence. The study aimed to determine mortality rates of the Australian
      Treatment Outcome Study cohort over the period 2001-2015, and the years of
      potential life lost (YPLL). METHODS: The cohort consisted of 615 heroin users.
      Crude mortality rates per 1000 person years (PY) and Standardised Mortality
      Ratios (SMR) were calculated. YPLL were calculated using two criteria: years lost
      prior to age 65, and years lost prior to average life expectancy. RESULTS: The
      cohort was followed for 7,790.9 PY. At 2015, 72 (11.7%) of the cohort were
      deceased, with a crude mortality rate of 9.2 per 1000 PYs. Neither age nor gender
      associated with mortality. The SMR was 10.2 (males 7.3, females 17.2), matched
      for age, gender and year of death. The most common mortality cause was opioid
      overdose (52.8%). Using the<65 years criterion, there were 1988.3 YPLL, with a
      mean of 27.6 (males 27.6, females 27.7). Using the average life expectancy
      criterion, there were 3135.1 YPLL, with a mean of 43.5 (males 41.9, females
      46.3). Accidental overdose (<65 yr 63.0%, average life expectancy 63.7%) and
      suicide (<65 yr 12.8%, average life expectancy 13.3%) accounted for three
      quarters of YPLL where cause of death was known. CONCLUSIONS: YPLL associated
      with heroin use was a quarter of a century, or close to half a century, depending
      on the criteria used. Given the prominent role of overdose and suicide, the
      majority of these fatalities, and the associated YPLL, appear preventable.

PMID- 27021807
TI  - Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal
      detection of particles in microfluidic channels.
AB  - Numerous biophysical and biochemical assays rely on spatial manipulation of
      particles/cells as they are processed on lab-on-a-chip devices. Analysis of
      spatially distributed particles on these devices typically requires microscopy
      negating the cost and size advantages of microfluidic assays. In this paper, we
      introduce a scalable electronic sensor technology, called microfluidic CODES,
      that utilizes resistive pulse sensing to orthogonally detect particles in
      multiple microfluidic channels from a single electrical output. Combining the
      techniques from telecommunications and microfluidics, we route three coplanar
      electrodes on a glass substrate to create multiple Coulter counters producing
      distinct orthogonal digital codes when they detect particles. We specifically
      design a digital code set using the mathematical principles of Code Division
      Multiple Access (CDMA) telecommunication networks and can decode signals from
      different microfluidic channels with >90% accuracy through computation even if
      these signals overlap. As a proof of principle, we use this technology to detect
      human ovarian cancer cells in four different microfluidic channels fabricated
      using soft lithography. Microfluidic CODES offers a simple, all-electronic
      interface that is well suited to create integrated, low-cost lab-on-a-chip
      devices for cell- or particle-based assays in resource-limited settings. 

PMID- 27021808
TI  - Spontaneous resolution of cryptogenic organizing pneumonia in pediatrics: A case
      report.
AB  - Cryptogenic organizing pneumonia (COP) is a rare entity in childhood,
      particularly in previously healthy children. Moreover, the spontaneous remission
      of the disease is exceptional. We report on the case of a previously healthy 10
      year-old girl who consulted her doctor for a 2-month history of mild pyrexia,
      fatigue, weight loss, and exertional dyspnea with no response to amoxicillin. A
      chest CT revealed bilateral, asymmetrical peribronchovascular consolidation areas
      predominating in the lower lobes and imaging features of COP. The bronchoalveolar
      lavage and the biological findings were negative. On follow-up, the girl showed
      clinical and radiological remission of the disease with no treatment. Our report
      describes an extremely rare case of spontaneously resolving COP in a child, the
      diagnosis being made based on the imaging pattern. 

PMID- 27021809
TI  - [Rhinovirus during childhood: Asthma at adolescence? The chicken or the egg
      causality dilemma].

PMID- 27021810
TI  - [Guillain-Barre syndrome with preserved reflexes].
AB  - Guillain-Barre is a rare, autoimmune disease of the peripheral nervous system. It
      can affect all ages beginning in the intrauterine or neonatal period. Clinical
      forms are diverse and include acute motor axonal neuropathy (AMAN). We report on
      a pediatric case of AMAN. A 2.5-year-old child presented with acute flaccid
      paralysis and preserved reflexes. Etiologic investigations argued in favor of
      Guillain-Barre syndrome in its AMAN form. Treatment based on IV immunoglobulins
      resulted in a total decline of paralysis and motor recovery. The AMAN form of
      Guillain-Barre syndrome should be considered as a potential diagnosis in all
      cases of acute flaccid paralysis with preserved reflexes. 

PMID- 27021811
TI  - Corrigendum: TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy
      with impaired retrograde intraflagellar transport.

PMID- 27021812
TI  - Legal Considerations for Health Care Practitioners After Superstorm Sandy.
AB  - During disaster response and recovery, legal issues often arise related to the
      provision of health care services to affected residents. Superstorm Sandy led to
      the evacuation of many hospitals and other health care facilities and compromised
      the ability of health care practitioners to provide necessary primary care. This
      article highlights the challenges and legal concerns faced by health care
      practitioners in the aftermath of Sandy, which included limitations in scope of
      practice, difficulties with credentialing, lack of portability of practitioner
      licenses, and concerns regarding volunteer immunity and liability. Governmental
      and nongovernmental entities employed various strategies to address these
      concerns; however, legal barriers remained that posed challenges throughout the
      Superstorm Sandy response and recovery period. We suggest future approaches to
      address these legal considerations, including policies and legislation,
      additional waivers of law, and planning and coordination among multiple levels of
      governmental and nongovernmental organizations. (Disaster Med Public Health
      Preparedness. 2016;10:518-524).

PMID- 27021813
TI  - A brief proposal for improving clinical trials.

PMID- 27021814
TI  - Amyloid-beta and hyperphosphorylated tau synergy drives metabolic decline in
      preclinical Alzheimer's disease.
AB  - This study was designed to test the interaction between amyloid-beta and tau
      proteins as a determinant of metabolic decline in preclinical Alzheimer's disease
      (AD). We assessed 120 cognitively normal individuals with [18F]florbetapir
      positron emission tomography (PET) and cerebrospinal fluid (CSF) measurements at
      baseline, as well as [18F]fluorodeoxyglucose ([18F]FDG) PET at baseline and at 24
      months. A voxel-based interaction model was built to test the associations
      between continuous measurements of CSF biomarkers, [18F]florbetapir and [18F]FDG
      standardized uptake value ratios (SUVR). We found that the synergistic
      interaction between [18F]florbetapir SUVR and CSF phosphorylated tau (p-tau)
      measurements, rather than the sum of their independent effects, was associated
      with a 24-month metabolic decline in basal and mesial temporal, orbitofrontal,
      and anterior and posterior cingulate cortices (P<0.001). In contrast,
      interactions using CSF amyloid-beta1-42 and total tau biomarkers did not
      associate with metabolic decline over a time frame of 24 months. The interaction
      found in this study further support the framework that amyloid-beta and
      hyperphosphorylated tau aggregates synergistically interact to cause downstream
      AD neurodegeneration. In fact, the regions displaying the metabolic decline
      reported here were confined to brain networks affected early by amyloid-beta
      plaques and neurofibrillary tangles. Preventive clinical trials may benefit from
      using a combination of amyloid-beta PET and p-tau biomarkers to enrich study
      populations of cognitively normal subjects with a high probability of disease
      progression in studies, using [18F]FDG as a biomarker of efficacy.

PMID- 27021815
TI  - Age and Alzheimer's disease gene expression profiles reversed by the glutamate
      modulator riluzole.
AB  - Alzheimer's disease (AD) and age-related cognitive decline represent a growing
      health burden and involve the hippocampus, a vulnerable brain region implicated
      in learning and memory. To understand the molecular effects of aging on the
      hippocampus, this study characterized the gene expression changes associated with
      aging in rodents using RNA-sequencing (RNA-seq). The glutamate modulator,
      riluzole, which was recently shown to improve memory performance in aged rats,
      prevented many of the hippocampal age-related gene expression changes. A
      comparison of the effects of riluzole in rats against human AD data sets revealed
      that many of the gene changes in AD are reversed by riluzole. Expression changes
      identified by RNA-Seq were validated by qRT-PCR open arrays. Riluzole is known to
      increase the glutamate transporter EAAT2's ability to scavenge excess glutamate,
      regulating synaptic transmission. RNA-seq and immunohistochemistry confirmed an
      increase in EAAT2 expression in hippocampus, identifying a possible mechanism
      underlying the improved memory function after riluzole treatment.

PMID- 27021816
TI  - Pathways to smoking behaviours: biological insights from the Tobacco and Genetics
      Consortium meta-analysis.
AB  - By running gene and pathway analyses for several smoking behaviours in the
      Tobacco and Genetics Consortium (TAG) sample of 74 053 individuals, 21 genes and
      several chains of biological pathways were implicated. Analyses were carried out
      using the HYbrid Set-based Test (HYST) as implemented in the Knowledge-based
      mining system for Genome-wide Genetic studies software. Fifteen genes are novel
      and were not detected with the single nucleotide polymorphism-based approach in
      the original TAG analysis. For quantity smoked, 14 genes passed the false
      discovery rate of 0.05 (corrected for multiple testing), with the top association
      signal located at the IREB2 gene (P=1.57E-37). Three genomic loci were
      significantly associated with ever smoked. The top signal is located at the
      noncoding antisense RNA transcript BDNF-AS (P=6.25E-07) on 11p14. The SLC25A21
      gene (P=2.09E-08) yielded the top association signal in the analysis of smoking
      cessation. The 19q13 noncoding RNA locus exceeded the genome-wide significance in
      the analysis of age at initiation (P=1.33E-06). Pathways belonging to the
      Neuronal system pathways, harbouring the nicotinic acetylcholine receptor genes
      expressing the alpha (CHRNA 1-9), beta (CHRNB 1-4), gamma, delta and E subunits,
      yielded the smallest P-values in the pathway analysis of the quantity smoked
      (lowest P=4.90E-42). Additionally, pathways belonging to 'a subway map of cancer
      pathways' regulating the cell cycle, mitotic DNA replication, axon growth and
      synaptic plasticity were found significantly enriched for genetic variants in
      ever smokers relative to never smokers (lowest P=1.61E-07). In addition, these
      pathways were also significantly associated with the quantity smoked (lowest
      P=4.28E-17). Our results shed light on one of the world's leading causes of
      preventable death and open a path to potential therapeutic targets. These results
      are informative in decoding the biological bases of other disease traits, such as
      depression and cancers, with which smoking shares genetic vulnerabilities.

PMID- 27021817
TI  - Alterations in the expression of a neurodevelopmental gene exert long-lasting
      effects on cognitive-emotional phenotypes and functional brain networks:
      translational evidence from the stress-resilient Ahi1 knockout mouse.
AB  - Many psychiatric disorders are highly heritable and may represent the clinical
      outcome of early aberrations in the formation of neural networks. The placement
      of brain connectivity as an 'intermediate phenotype' renders it an attractive
      target for exploring its interaction with genomics and behavior. Given the
      complexity of genetic make up and phenotypic heterogeneity in humans,
      translational studies are indicated. Recently, we demonstrated that a mouse model
      with heterozygous knockout of the key neurodevelopmental gene Ahi1 displays a
      consistent stress-resilient phenotype. Extending these data, the current research
      describes our multi-faceted effort to link early variations in Ahi1 expression
      with long-term consequences for functional brain networks and cognitive-emotional
      phenotypes. By combining behavioral paradigms with graph-based analysis of whole
      brain functional networks, and then cross-validating the data with robust
      neuroinformatic data sets, our research suggests that physiological variation in
      gene expression during neurodevelopment is eventually translated into a continuum
      of global network metrics that serve as intermediate phenotypes. Within this
      framework, we suggest that organization of functional brain networks may result,
      in part, from an adaptive trade-off between efficiency and resilience, ultimately
      culminating in a phenotypic diversity that encompasses dimensions such as
      emotional regulation and cognitive function.

PMID- 27021819
TI  - Pharmacological enhancement of mGlu5 receptors rescues behavioral deficits in
      SHANK3 knock-out mice.
AB  - SHANK3 (also called PROSAP2) genetic haploinsufficiency is thought to be the
      major cause of neuropsychiatric symptoms in Phelan-McDermid syndrome (PMS). PMS
      is a rare genetic disorder that causes a severe form of intellectual disability
      (ID), expressive language delays and other autistic features. Furthermore, a
      significant number of SHANK3 mutations have been identified in patients with
      autism spectrum disorders (ASD), and SHANK3 truncating mutations are associated
      with moderate to profound ID. The Shank3 protein is a scaffold protein that is
      located in the postsynaptic density (PSD) of excitatory synapses and is crucial
      for synapse development and plasticity. In this study, we investigated the
      molecular mechanisms associated with the ASD-like behaviors observed in
      Shank3Delta11-/- mice, in which exon 11 has been deleted. Our results indicate
      that Shank3 is essential to mediating metabotropic glutamate receptor 5 (mGlu5)
      receptor signaling by recruiting Homer1b/c to the PSD, specifically in the
      striatum and cortex. Moreover, augmenting mGlu5-receptor activity by
      administering 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide ameliorated the
      functional and behavioral defects that were observed in Shank3Delta11-/- mice,
      suggesting that pharmaceutical treatments that increase mGlu5 activity may
      represent a new approach for treating patients that are affected by PMS and
      SHANK3 mutations.

PMID- 27021818
TI  - Alzheimer disease: modeling an Abeta-centered biological network.
AB  - In genetically complex diseases, the search for missing heritability is focusing
      on rare variants with large effect. Thanks to next generation sequencing
      technologies, genome-wide characterization of these variants is now feasible in
      every individual. However, a lesson from current studies is that collapsing rare
      variants at the gene level is often insufficient to obtain a statistically
      significant signal in case-control studies, and that network-based analyses are
      an attractive complement to classical approaches. In Alzheimer disease (AD),
      according to the prevalent amyloid cascade hypothesis, the pathology is driven by
      the amyloid beta (Abeta) peptide. In past years, based on experimental studies,
      several hundreds of proteins have been shown to interfere with Abeta production,
      clearance, aggregation or toxicity. Thanks to a manual curation of the
      literature, we identified 335 genes/proteins involved in this biological network
      and classified them according to their cellular function. The complete list of
      genes, or its subcomponents, will be of interest in ongoing AD genetic studies.

PMID- 27021820
TI  - Genome-wide interaction study of brain beta-amyloid burden and cognitive
      impairment in Alzheimer's disease.
AB  - The lack of strong association between brain beta-amyloid deposition and
      cognitive impairment has been a challenge for the Alzheimer's disease (AD) field.
      Although beta-amyloid is necessary for the pathologic diagnosis of AD, it is not
      sufficient to make the pathologic diagnosis or cause dementia. We sought to
      identify the genetic modifiers of the relation between cortical beta-amyloid
      burden (measured using [18F]Florbetapir-PET) and cognitive dysfunction (measured
      using ADAS-cog) by conducting a genome-wide interaction study on baseline data
      from participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI)
      phases GO/2 (n=678). Near genome-wide significant interaction effect was observed
      for rs73069071 within the IAPP (amylin) and SLCO1A2 genes (P=6.2 * 10-8).
      Congruent results were found using data from participants followed up from ADNI-1
      (Pone-tailed=0.028, n=165). Meta-analysis across ADNI-GO/2 and ADNI-1 revealed a
      genome-wide significant interaction effect (P=1.1 * 10-8). Our results were
      further supported by similar interaction effects on temporal lobe cortical
      thickness (whole-brain voxelwise analysis: familywise error corrected P=0.013)
      and longitudinal changes in ADAS-cog score and left middle temporal thickness and
      amygdalar volume (Pone-tailed=0.026, 0.019 and 0.003, respectively). Using
      postmortem beta-amyloid immunohistochemistry data from 243 AD participants in the
      Religious Orders Study and Memory and Aging Project, we also observed similar
      rs73069071-by-beta-amyloid deposition interaction effect on global cognitive
      function (Pone-tailed=0.005). Our findings provide insight into the complexity of
      the relationship between beta-amyloid burden and AD-related cognitive impairment.
      Although functional studies are required to elucidate the role of rs73069071 in
      AD pathophysiology, our results support the recently growing evidence on the role
      of amylin in AD.

PMID- 27021821
TI  - Alcohol affects brain functional connectivity and its coupling with behavior:
      greater effects in male heavy drinkers.
AB  - Acute and chronic alcohol exposure significantly affect behavior but the
      underlying neurobiological mechanisms are still poorly understood. Here, we used
      functional connectivity density (FCD) mapping to study alcohol-related changes in
      resting brain activity and their association with behavior. Heavy drinkers (HD,
      N=16, 16 males) and normal controls (NM, N=24, 14 males) were tested after
      placebo and after acute alcohol administration. Group comparisons showed that NM
      had higher FCD in visual and prefrontal cortices, default mode network regions
      and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly
      increased FCD within the thalamus, impaired cognitive and motor functions, and
      affected self-reports of mood/drug effects in both groups. Partial least squares
      regression showed that alcohol-induced changes in mood/drug effects were
      associated with changes in thalamic FCD in both groups. Disruptions in motor
      function were associated with increases in cerebellar FCD in NM and thalamus FCD
      in HD. Alcohol-induced declines in cognitive performance were associated with
      connectivity increases in visual cortex and thalamus in NM, but in HD, increases
      in precuneus FCD were associated with improved cognitive performance. Acute
      alcohol reduced 'neurocognitive coupling', the association between behavioral
      performance and FCD (indexing brain activity), an effect that was accentuated in
      HD compared with NM. Findings suggest that reduced cortical connectivity in HD
      contribute to decline in cognitive abilities associated with heavy alcohol
      consumption, whereas increased cerebellar connectivity in HD may have
      compensatory effects on behavioral performance. The results reveal how drinking
      history alters the association between brain FCD and individual differences in
      behavioral performance.

PMID- 27021822
TI  - Genetic overlap between type 2 diabetes and depression in Swedish and Danish twin
      registries.
AB  - A bidirectional association between type 2 diabetes (T2DM) and depression has
      been consistently reported. Depression is associated with worse biomedical
      outcomes and increased mortality. The mechanisms underlying the association of
      T2DM with depression remain unclear. One possible question we can address is the
      extent to which the co-occurrence of diabetes and depression is due to correlated
      genetic and/or environmental risk factors. In this study, we performed structural
      equation model fitting to population-level data from the Swedish (n=68 606) and
      Danish (n=95 403) twin registries. The primary outcomes were clinical diagnosis
      of T2DM and depression using national hospital discharge registries. The
      phenotypic correlation between T2DM and depression is modest in both samples. In
      the Swedish sample, unique environmental effects explain a greater proportion of
      the covariance in males, whereas the association is primarily attributed to
      genetic effects in females. In the Danish sample, genetic effects account for the
      majority of the covariance in both males and females. Qualitative genetic sex
      differences are observed in both samples. We believe this is the first study to
      demonstrate significant genetic overlap between T2DM and depression.

PMID- 27021824
TI  - Analysis of Driving Factors of Willingness to Use and Willingness to Pay for
      Existing Pharmacological Smoking Cessation Aids Among Young and Middle-Aged
      Adults in Germany.
AB  - BACKGROUND: Smoking cessation is a challenging task with a high risk of relapse.
      Depending on the choice of medication and duration of therapy, the costs of using
      a smoking cessation aid can be high. Additionally, these costs are not covered by
      health insurance in Germany. Information on willingness to use (WTU) and
      willingness to pay (WTP) for smoking cessation aids is valuable for developing
      different smoking cessation strategies. OBJECTIVES: The study analyses WTU and
      WTP for three pharmacological smoking cessation aids (nicotine replacement
      therapy (NRT), bupropion and varenicline) among young and middle-aged adults in
      Germany and attempts to determine their major driving factors. METHODS: Two cross
      sectional internet-based surveys of smokers over 18 years of age were conducted
      in 2014 and 2015 in Germany. Respondents were asked about smoking-related issues
      and WTU and WTP for each therapy. The contingent valuation method with payment
      cards was used to measure WTP. Descriptive statistics, logistical regression and
      accelerated failure-time regression models were performed. RESULTS: The total
      sample size is 505. Half of the respondents are willing to use NRT and one-third
      are willing to use bupropion and/or varenicline. WTU induces positive WTP;
      however, the magnitude of WTP is beneath the market price. WTU significantly
      increases with a higher addiction level and if smokers have previously heard
      about the therapy. CONCLUSION: This study indicates different points to be
      considered for policy development. Promotion information and improving awareness
      about medication aids might increase WTU, and development of monetary incentives
      for young smokers could create a better chance for successful smoking cessation.

PMID- 27021825
TI  - What can pestiviral endonucleases teach us about innate immunotolerance?
AB  - Pestiviruses including bovine viral diarrhea virus (BVDV), border disease virus
      (BDV) and classical swine fever virus (CSFV), occur worldwide and are important
      pathogens of livestock. A large part of their success can be attributed to the
      induction of central immunotolerance including B- and T-cells upon fetal
      infection leading to the generation of persistently infected (PI) animals. In the
      past few years, it became evident that evasion of innate immunity is a central
      element to induce and maintain persistent infection. Hence, the viral non
      structural protease N(pro) heads the transcription factor IRF-3 for proteasomal
      degradation, whereas an extracellularly secreted, soluble form of the envelope
      glycoprotein E(rns) degrades immunostimulatory viral single- and double-stranded
      RNA, which makes this RNase unique among viral endoribonucleases. We propose that
      these pestiviral interferon (IFN) antagonists maintain a state of innate
      immunotolerance mainly pertaining its viral nucleic acids, in contrast to the
      well-established immunotolerance of the adaptive immune system, which is mainly
      targeted at proteins. In particular, the unique extension of 'self' to include
      the viral genome by degrading immunostimulatory viral RNA by E(rns) is
      reminiscent of various host nucleases that are important to prevent inappropriate
      IFN activation by the host's own nucleic acids in autoimmune diseases such as
      Aicardi-Goutieres syndrome or systemic lupus erythematosus. This mechanism of
      "innate tolerance" might thus provide a new facet to the role of extracellular
      RNases in the sustained prevention of the body's own immunostimulatory RNA to act
      as a danger-associated molecular pattern that is relevant across various species.

PMID- 27021823
TI  - Transgenerational transmission and modification of pathological traits induced by
      prenatal immune activation.
AB  - Prenatal exposure to infectious or inflammatory insults is increasingly
      recognized to contribute to the etiology of psychiatric disorders with
      neurodevelopmental components, including schizophrenia, autism and bipolar
      disorder. It remains unknown, however, if such immune-mediated brain anomalies
      can be transmitted to subsequent generations. Using an established mouse model of
      prenatal immune activation by the viral mimetic poly(I:C), we show that reduced
      sociability and increased cued fear expression are similarly present in the first
      and second-generation offspring of immune-challenged ancestors. We further
      demonstrate that sensorimotor gating impairments are confined to the direct
      descendants of infected mothers, whereas increased behavioral despair emerges as
      a novel phenotype in the second generation. These transgenerational effects are
      mediated via the paternal lineage and are stable until the third generation,
      demonstrating transgenerational non-genetic inheritance of pathological traits
      following in-utero immune activation. Next-generation sequencing further
      demonstrated unique and overlapping genome-wide transcriptional changes in first-
      and second-generation offspring of immune-challenged ancestors. These
      transcriptional effects mirror the transgenerational effects on behavior, showing
      that prenatal immune activation leads to a transgenerational transmission
      (presence of similar phenotypes across generations) and modification (presence of
      distinct phenotypes across generations) of pathological traits. Together, our
      study demonstrates for, we believe, the first time that prenatal immune
      activation can negatively affect brain and behavioral functions in multiple
      generations. These findings thus highlight a novel pathological aspect of this
      early-life adversity in shaping disease risk across generations.

PMID- 27021826
TI  - Chemokine regulation of neutrophil function in tumors.
AB  - The role of neutrophils in cancer and metastasis is still debated and
      controversial since they have been shown to be endowed with both pro- and
      antitumor functions. These contradictory results seem to be now explained by
      recent discoveries of tumor-associated neutrophils plasticity and multiple
      neutrophil subsets. Chemokines and chemokine receptors are known to tightly
      regulate the release of neutrophils from the bone marrow, their passage into
      circulation and transmigration into the tissues as well as tumor infiltration. It
      is emerging that chemokine receptors are differentially expressed by neutrophil
      subsets and they affect not only their recruitment but also their effector
      functions. Here we are resuming human and murine data suggesting that therapeutic
      modulation of neutrophil activity through the targeting of specific chemokines or
      chemokine receptors can improve their anti-tumoral properties.

PMID- 27021827
TI  - Inflammatory microenvironment and human papillomavirus-induced carcinogenesis.
AB  - More than 15% of the global cancer burden is attributable to infectious agents.
      Pathogens that cause persistent infections are strongly associated with cancer,
      inflammation being a major component of the chronic infections as revealed by
      basic, clinical and epidemiological studies. Persistent infection and viral
      oncoproteins induce specific cellular pathways modifications that promote
      tumorigenesis. Deregulated and continuous immune response leads to severe tissue
      and systemic damage, impaired tumor surveillance and consequent carcinogenesis
      promotion by selecting for metastatic and therapeutically resistant tumor
      phenotypes. In this review, the role of inflammatory microenvironment in the HPV
      induced carcinogenesis is addressed, with a specific focus on the involvement of
      the immune molecules and microRNAs as well as their delivery through the
      microvesicle cargo.

PMID- 27021828
TI  - Fatigue in Irritable Bowel Syndrome: A Systematic Review and Meta-analysis of
      Pooled Frequency and Severity of Fatigue.
AB  - PURPOSE: Fatigue is the third most common "extraintestinal" complaint of patients
      with irritable bowel syndrome (IBS), but it is still poorly understood. This
      study aimed to review characteristics of IBS-associated fatigue and to examine
      pooled frequency, severity of fatigue, and correlations of related factors with
      fatigue in IBS via meta-analyses. METHODS: Publications were searched in eight
      databases from 1995 to 2014. Random effects meta-analyses were applied with
      standard error, weighted effect size, and correlation-based measure of effect
      size. RESULTS: Twenty-four studies were included in systematic review. Seventeen
      studies were used for meta-analyses (2 studies were excluded in the frequency of
      fatigue analysis due to data unavailability). Using "tiredness" to define
      fatigue, and Fatigue Impact Scale to assess fatigue were the most frequently used
      across the studies. Gastrointestinal symptoms, psychological distress, and health
      related quality of life were the most common correlates with fatigue. The pooled
      frequency of fatigue was 54.2% [95% confidence interval (38.5, 69.4)].
      Metaregression on the frequency of fatigue showed positive and significant
      relations with tertiary care settings, female sex, and younger age. There was a
      negatively moderate relationship between the severity of fatigue and health
      related quality of life score (correlation-based measure of effect size: -.378).
      CONCLUSIONS: Fatigue is prevalent among patients with IBS and commonly co-occurs
      with other symptoms. This is the first study to fully examine fatigue in IBS,
      which shed light on the comprehensive management of fatigue in this patient
      group. Future research is warranted to further explore fatigue-related factors
      and underlying mechanisms of fatigue in IBS.

PMID- 27021829
TI  - Parent Involvement Intervention in Developing Weight Management Skills for both
      Parents and Overweight/Obese Children.
AB  - PURPOSE: The purpose of the study was to evaluate a parent involvement
      intervention for childhood obesity intended to increase parents' skills in
      managing children's weight-related behavior and to improve child-parent
      relationships. Many studies reported on parental influence on childhood obesity,
      emphasizing parent involvement in prevention and management of childhood obesity.
      METHODS: A randomized controlled trial was conducted. Forty-two parents of
      overweight/obese children were recruited from four cities and randomized to the
      experimental group or control group. The parental intervention was provided only
      to parents in the experimental group and consisted of weekly newsletters and text
      messages for a period of 5 weeks. Exercise classes and nutrition education were
      provided to all children. Lifestyle Behaviour Checklist and the Child-Parent
      Relationship Scale (CPRS) were used for measurement of parent outcome. For the
      child outcome, dietary self-efficacy, exercise frequency, and body mass index
      were measured. A mixed-design analysis of variance was performed with city
      location entered as a random effect. RESULTS: After the intervention, CPRS of
      parents and dietary self-efficacy of children showed an increase in the
      experimental group (p < .05). Intervention effects differed significantly
      according to the city location regarding the control efficacy of parents and
      dietary self-efficacy of children (p < .05). CONCLUSIONS: The results support the
      effectiveness of the parent involvement intervention in promoting child-parent
      relationship and dietary self-efficacy of children. However, a 5-week parent
      involvement intervention was not sufficient to produce significant changes in
      children's body mass index. Further research is needed to investigate effects of
      parent involvement intervention with long-term evaluation.

PMID- 27021830
TI  - Relationships between Personal Traits, Emotional Intelligence, Internal
      Marketing, Service Management, and Customer Orientation in Korean Outpatient
      Department Nurses.
AB  - PURPOSE: Current increase and complexity of medical tests and surgical procedures
      at outpatient department (OPD) require OPD nurses to have customer orientation
      focusing on various customers' interests and needs. The purpose of this study was
      to identify the factors associated with customer orientation in nurses working at
      OPD of hospitals. METHODS: The study used a descriptive correlational design with
      cross-sectional survey. The study settings were four general hospitals in Seoul
      and its metropolitan area. Data were collected from 138 OPD nurses from general
      hospitals. Study variables were personal traits, emotional intelligence, internal
      marketing, service management and customer orientation. RESULTS: Factors
      associated with customer orientation were identified as conscientiousness from
      personal traits (beta = .37, p < .001), emotional intelligence from individual
      characteristics (beta = .21, p = .032), and internal marketing from environmental
      characteristics (beta = .21, p = .001). CONCLUSIONS: Hospital administrators
      should support OPD nurses to cultivate sincere and sociable personal traits and
      emotional intelligence, and to consider employees as internal customers to
      improve patient-oriented services and satisfaction.

PMID- 27021831
TI  - Health Promotion Behavior of Chinese International Students in Korea Including
      Acculturation Factors: A Structural Equation Model.
AB  - PURPOSE: The purpose of this study was to explain the health promotion behavior
      of Chinese international students in Korea using a structural equation model
      including acculturation factors. METHOD: A survey using self-administered
      questionnaires was employed. Data were collected from 272 Chinese students who
      have resided in Korea for longer than 6 months. The data were analyzed using
      structural equation modeling. RESULTS: The p value of final model is .31. The
      fitness parameters of the final model such as goodness of fit index, adjusted
      goodness of fit index, normed fit index, non-normed fit index, and comparative
      fit index were more than .95. Root mean square of residual and root mean square
      error of approximation also met the criteria. Self-esteem, perceived health
      status, acculturative stress and acculturation level had direct effects on health
      promotion behavior of the participants and the model explained 30.0% of variance.
      CONLCUSIONS: The Chinese students in Korea with higher self-esteem, perceived
      health status, acculturation level, and lower acculturative stress reported
      higher health promotion behavior. The findings can be applied to develop health
      promotion strategies for this population.

PMID- 27021832
TI  - Sickness Experiences of Korean Registered Nurses at Work: A Qualitative Study on
      Presenteeism.
AB  - PURPOSE: Presenteeism is a relatively new concept in nursing describing the
      condition within which registered nurses (RNs) come to work while they are sick.
      The purpose of this study was to explore and describe presenteeism experiences
      among RNs in South Korea. METHODS: In this constructivist grounded theory study,
      a focus group interview (FGI) technique was utilized for data collection. A total
      of 20 RNs at one hospital in Chuncheon city joined in three different FGIs.
      Semistructured questions were asked in reference to their sickness experience in
      the workplace. Data analysis was conducted according to the constructivist
      grounded theory methodology. RESULTS: All participants had experiences of
      presenteeism. The overriding theme was "having no caring for nurses leads to
      losing one's nursing mind". The participants reported that due to either their
      personal preference or peer pressure they showed up to work, but they felt sad
      and their pride was hurt by the fact that there was no caring for them from other
      nurses. This emotional exhaustion often led to the loss of compassion and the
      resignation of nursing staff. CONCLUSIONS: Care for nurses in the workplace is
      necessary for RNs to make their presenteeism experience positive and even
      effective.

PMID- 27021833
TI  - Psychometric Testing of Behavior Assessment for Children.
AB  - PURPOSE: The purpose of this study was to test the reliability and validity of
      the Behavior Assessment for Children (BAC) in a community of school-aged children
      in Taiwan. METHOD: A school-based sample comprising third grade and fourth grade
      students was recruited from Taichung City in Taiwan. The parents (n = 248) and
      teachers (n = 15) of these students completed structured questionnaires,
      including the Child Behavior Checklist (CBCL) and the proposed BAC. Content
      validity, concurrent validity, construct validity, internal consistency, and
      inter-rater reliability of the BAC were assessed. RESULTS: The BAC comprised
      three subscales (attention, emotion, and self-control) that included 17 items.
      The content validity index (CVI) score was 0.98. The result of the confirmatory
      factor analysis (goodness of fit = .90, root mean square of residual = .03, root
      mean square error of approximation = .06, and comparative fit index = .94)
      supported the construct validity of the three BAC subscales. The concurrent
      validity of the BAC subscales significantly correlated with the compatible CBCL
      subscales (r = .59-.78, p < .001). Cronbach alpha of the subscales of the BAC
      ranged from .78 to .92. The intraclass correlation coefficient between the
      parents and teachers ranged from .31 to .44, and the joint probability of
      agreement ranged from 31.4% to 92.2%. CONCLUSIONS: The BAC is a valid and
      reliable instrument for evaluating behavioral problems in school-aged children.

PMID- 27021834
TI  - Perceived Risk of Human Papillomavirus Infection and Cervical Cancer among
      Adolescent Women in Taiwan.
AB  - PURPOSE: High-risk types of human papillomavirus (HPV) are a critical etiologic
      factor behind cervical cancer. Adolescents are a vulnerable group for HPV
      infection. However, the literature on adolescent women for HPV infection and
      cervical cancer is limited. This study was to investigate HPV-related knowledge
      and perceived risk of HPV infection and cervical cancer among Taiwanese
      adolescent women in order to assess intervention strategies for prevention of
      cervical cancer and maintenance of reproductive health. METHODS: A descriptive
      cross-sectional study design was implemented. There were 610 adolescent women
      from three colleges in Southern Taiwan who participated in this study. Data were
      collected using an anonymous self-administered questionnaire survey. RESULTS: The
      results showed that the percentage of appropriate answers to HPV-related
      knowledge questions was only 36.8%, and smoking as the leading cause of cervical
      cancer received the lowest mean score for appropriate answers among the HPV
      related knowledge items. The perceived risk of HPV infection and cervical cancer
      were moderate, with relatively lower susceptibility to infection with HPV than to
      cervical cancer (p < .001). Only 11.5% of the participants reported that they had
      received information about HPV vaccination from healthcare professionals.
      CONCLUSIONS: Participants lacked a comprehensive understanding of cervical cancer
      prevention and were not aware of their susceptibility to HPV infection.
      Adolescent women rarely obtained HPV-related information from healthcare
      professionals. Appropriate education strategies should be developed and conducted
      by healthcare professionals to reduce the risk of cervical cancer threat from
      adolescence.

PMID- 27021835
TI  - Differences in Functional Fitness Among Older Adults With and Without Risk of
      Falling.
AB  - PURPOSE: This study aimed to identify the differences in functional fitness
      between older adults who were at risk of falling and those who were not. METHODS:
      A total of 104 older adults aged 65-74 years were recruited from a local
      community senior center. They were independent older adults without a history of
      falls in the preceding 12 months. Falling risk status was assessed using the Fall
      Risk Test. Five dimensions of functional fitness with seven testing parameters
      (i.e., 30-second chair stand test, 30-second arm curl test, 2-minute step test,
      chair sit and reach test, back scratch test, 8-foot up and go test, and body mass
      index) were evaluated by the Senior Fitness Test. RESULTS: Only 78 participants
      completed all the tests, of which 48 participants were identified with risk of
      falling, and 30 participants were free from risk of falling. Results from
      multivariate analysis of variance found significant differences on the combined
      outcome variables, especially in the 8-foot up and go test, 2-minute step test,
      and 30-second arm curl test. Results from discriminant analysis found a
      significant discriminant function among all the seven testing parameters, where
      the 8-foot up and go test, and the 2-minute step test contributed most.
      CONCLUSIONS: Older adults who are at the early stage of risk of falling tend to
      have lower functional fitness capacities, especially in agility and dynamic
      balance, aerobic endurance as well as in a combined relationship among all the
      testing parameters.

PMID- 27021836
TI  - Factors Influencing University Nursing Students' Measles Vaccination Rate During
      a Community Measles Outbreak.
AB  - PURPOSE: The purpose of this study was to survey the current state of measles
      vaccination in university nursing students during a measles outbreak and to
      identify factors influencing nursing students' vaccination rate. METHODS: In
      2014, this study used a self-administered questionnaire to survey 380 university
      nursing students. Factors influencing measles vaccination were identified through
      logistic regression analysis using variables between the vaccinated and
      nonvaccinated groups. RESULTS: Measles vaccination rate was 52.1%. The
      vaccination rate was significantly higher in juniors, seniors, and those who had
      heard about measles. In relation to health beliefs, the measles vaccination rate
      was higher when perceived benefits were high and perceived barriers were low.
      CONCLUSIONS: A systematic measles vaccination program targeting nursing students
      upon their entry to university is needed. In order to increase the measles
      vaccination rate, application of effective promotion campaigns and education
      programs is necessary.

PMID- 27021837
TI  - Psychometric Properties of Turkish Version of Pediatric Daytime Sleepiness Scale
      (PDSS-T).
AB  - PURPOSE: The aim of the research was to evaluate the psychometric properties of
      the Pediatric Daytime Sleepiness Scale-Turkish Version (PDSS-T). METHODS: The
      researchers chose a study sample of 522 grade 5-11 students. Data were collected
      using a demographic data collection form and the PDSS-T. RESULTS: Cronbach alpha
      for the scale was .79 and Kaiser-Meyer-Olkin coefficient was .78. Item-total
      correlations for the scale varied between .53 and .73 (p < .001). The indices of
      model fit were determined to be the root mean square error of approximation at
      .07, the goodness of fit index at .97, and the comparative fit index at .97.
      CONCLUSIONS: The study's results showed that PDSS-T is a valid and reliable
      instrument for detecting Turkish-speaking children's and adolescents' daytime
      sleepiness. PDSS-T is convenient for professionals to prevent and manage daytime
      sleepiness.

PMID- 27021838
TI  - Vocational Identity and Ego Identity Status in Korean Nursing Students.
AB  - PURPOSE: The purpose of this study was to investigate the association between
      vocational identity and ego identity status among Korean nursing students.
      METHODS: The participants were 311 nursing students in South Korea who were
      attending either a 4-year bachelor's program or a 3-year diploma program. Data
      were collected using self-report questionnaires that addressed vocational
      identity, ego identity status, and demographic information. The data were
      analyzed using descriptive statistics, one-way analysis of variance, t test, and
      Chi-square test. RESULTS: In terms of ego identity status, 31.5% of nursing
      students were classified as being in diffusion status, followed by 28.3% in low
      profile moratorium status, 14.8% in moratorium status, 14.1% in foreclosure
      status, and 11.3% in achievement status. Vocational identity differed according
      to ego identity status; vocational identity among students who were in
      achievement status was higher than for those in all other statuses. Vocational
      identity also differed according to grade level and monthly family income. Ego
      identity status was related to the type of program enrolled in, grade level, and
      monthly family income. CONCLUSIONS: These findings show that nursing students in
      identity achievement status have secure and clear vocational identities. Further
      longitudinal and qualitative studies are needed to find out if identity formation
      among nursing students changes with age.

PMID- 27021839
TI  - Predictors of Health Behaviors in Turkish Female Nursing Students.
AB  - PURPOSE: This study was conducted to determine the health behaviors of Turkish
      female baccalaureate nursing students and to examine the impact of
      sociodemographic and health-related factors and their mothers' health behaviors
      on the health behaviors of nursing students. METHODS: This cross-sectional study
      included 337 nursing students and 337 mothers. Data were collected using self
      administered questionnaires that included a personal information form, the
      Perception of Health Scale and the Health-Promoting Lifestyle Profile-II (HPLP
      II). Descriptive statistics, one-way analysis of variance, Student's t test,
      Pearson's correlation coefficients and linear regression analysis were used for
      data analysis. RESULTS: The total HPLP-II mean score of the students was 131.98
      +/- 17.15 (item M = 2.61, SD = 0.33). Among the subscales of the HPLP-II, the
      spiritual growth had the highest mean subscale score, followed by the
      interpersonal relations subscale, while the physical activity had the lowest mean
      subscale score. Significant predictors of health behaviors of the students were
      school year (unstandardized beta = .09, p = .012), total score for the Perception
      of Health Scale (unstandardized beta = .02, p < .001), and the mothers' total
      HPLP-II score (unstandardized beta = .33, p < .001), after controlling for
      specific variables. CONCLUSIONS: This study demonstrated that the students who
      were attending the first-year program, those with higher levels of perceptions of
      health and those whose mothers had better health behaviors were more likely to
      have better health behaviors. The results of this study emphasize the importance
      of making culturally appropriate interventions by taking into account the factors
      contributing to the health behaviors of nursing students.

PMID- 27021840
TI  - A Structural Equation Model Linking Health Literacy to Self-efficacy, Self-care
      Activities, and Health-related Quality of Life in Patients with Type 2 Diabetes.
AB  - PURPOSE: Health literacy has been attracting increasing attention because low
      health literacy is considered an important predictor of adverse health outcomes
      in many chronic conditions, including diabetes. However, it is unclear how health
      literacy is associated with health outcomes. The purpose of this study was to
      formulate a hypothetical structural equation model linking health literacy to
      self-efficacy, self-care activities, and health-related quality of life (HRQOL)
      in patients with type 2 diabetes. METHODS: A cross-sectional survey design was
      employed, and 459 patients with type 2 diabetes were recruited from outpatient
      clinics in two university hospitals. The patients completed a pack of
      questionnaires. The hypothetical model was tested using structural equation
      modeling analysis. RESULTS: The values of multiple fit indices indicated that the
      proposed model provided a good fit to the data. Health literacy exerted not only
      a direct effect on self-care activities, but also an indirect effect on self-care
      activities via self-efficacy. However, health literacy exerted only an indirect
      effect on HRQOL. This structural model was invariant across hemoglobin-A1c
      controlled and hemoglobin-A1c-uncontrolled groups. Based on R(2) values, the
      final model accounted for 20.0% of the variance in self-efficacy, 61.0% of the
      variance in self-care activities, and 16.0% of the variance in HRQOL.
      CONCLUSIONS: This study suggests that self-care activities are crucial to the
      link between health literacy and HRQOL. Both health literacy and self-efficacy
      need to be considered in clinical practice for enhancing self-care activities in
      patients with type 2 diabetes. This approach may ultimately improve HRQOL in
      these patients.

PMID- 27021841
TI  - A New Alternative for Difficult Ureter in Adult Patients: No Need to Dilate
      Ureter via a Balloon or a Stent with the Aid of 4.5F Semirigid Ureteroscope.
AB  - OBJECTIVE: To investigate the effectivity of 4.5F ultrathin ureteroscope (UT-URS)
      without any need for active or passive dilation in the treatment of adult patient
      population in whom ureteral orifices cannot be engaged using conventional URS.
      MATERIALS AND METHODS: Among a total of 512 adult patients who had undergone URS
      between April 2012 and November 2015 in our department for diagnostic or
      therapeutic purposes, 43 (8.4%) patients required ureteral dilation because we
      could not engage ureteral orifice. In adult patients in whom we could not engage
      ureteral orifice with 7.5F and 8F semirigid URS, we tried to complete the
      operation using 4.5F UT-URS without resorting to dilation. Age and gender of the
      patients, indication for operation, stone size, location, operative times,
      laterality of stone(s), stone-free rates, length of hospital stay, and
      complications were recorded. RESULTS: Mean age of the patients was 34.5 +/- 11.2
      (21-66) years. The patients had undergone operations for ureteral stone (n = 39),
      unexplained hydronephrosis (n = 2), and ureteral stenosis (n = 2). Mean stone
      size was 8.2 +/- 2.3 (4-18) mm. Mean operative time was 64.2 +/- 13.5 minutes. In
      37 of 39 patients, a complete stone-free rate (94.8%) was achieved. Mean length
      of hospital stay was 8.9 +/- 5.8 hours. CONCLUSION: It has been demonstrated that
      in an adult patient population in whom ureteral orifices cannot be engaged using
      conventional URS, ureteral access could be achieved with 4.5F UT-URS without any
      need for dilation. At the same time, use of 4.5F UT-URS resulted in an acceptable
      treatment success and lower complication rates in most of these patients without
      the need for a second session.

PMID- 27021842
TI  - Characterizing novel metabolic pathways of melatonin receptor agonist agomelatine
      using metabolomic approaches.
AB  - Agomelatine (AGM), an analog of melatonin, is a potential agonist at melatonin
      receptors 1/2 and a selective antagonist at 5-hydroxytryptamine 2C receptors. AGM
      is widely used for the treatment of major depressive episodes in adults. However,
      multiple adverse effects associated with AGM have been reported in clinical
      practice. It is little known about AGM metabolism in vitro and in vivo, although
      metabolism plays a pivotal role in its efficacy and safety. To elucidate
      metabolic pathways of AGM, we systemically investigated AGM metabolism and its
      bioactivation in human liver microsomes (HLM) and mice using metabolomic
      approaches. We identified thirty-eight AGM metabolites and adducts, among which
      thirty-two are novel. In HLM, we uncovered five GSH-trapped adducts and two
      semicarbazide-trapped aldehydes. Moreover, we characterized three N-acetyl
      cysteine conjugated-AGM adducts in mouse urine and feces, which were formed from
      the degradation of AGM_GSH adducts. Using recombinant CYP450 isoenzymes and
      chemical inhibitors, we demonstrated that CYP1A2 and CYP3A4 are primary enzymes
      contributing to the formation of AGM_GSH adducts and AGM_hydrazones. This study
      provided a global view of AGM metabolism and identified the novel pathways of AGM
      bioactivation, which could be utilized for further understanding the mechanism of
      adverse effects related to AGM and possible drug-drug interactions.

PMID- 27021843
TI  - Proteomic analysis to elucidate degeneration of Clostridium beijerinckii NCIMB
      8052 and role of Ca(2+) in strain recovery from degeneration.
AB  - Degeneration of solventogenic Clostridium strains is one of the major barriers in
      bio-butanol production. A degenerated Clostridium beijerinckii NCIMB 8052 strain
      (DG-8052) was obtained without any genetic manipulation. Supplementation of CaCO3
      to fermentation medium could partially recover metabolism of DG-8052 by more than
      50 % increase of cell growth and solvent production. This study investigated the
      protein expression profile of DG-8052 and its response to CaCO3 treatment.
      Compared with WT-8052, the lower expressed proteins were responsible for
      disruption of RNA secondary structures and DNA repair, sporulation, signal
      transduction, transcription regulation, and membrane transport in DG-8052.
      Interestingly, accompanied with the decreased glucose utilization and lower
      solvent production, there was a decreased level of sigma-54 modulation protein
      which may indicate that the level of sigma-54 activity may be associated with the
      observed strain degeneration. For the addition of CaCO3, proteomic and
      biochemical study results revealed that besides buffer capacity, Ca(2+) could
      stabilize heat shock proteins, increase DNA synthesis and replication, and
      enhance expression of solventogenic enzymes in DG-8052, which has a similar
      contribution in WT-8052.

PMID- 27021844
TI  - Linkages of Firmicutes and Bacteroidetes populations to methanogenic process
      performance.
AB  - To identify potential linkages between specific bacterial populations and process
      performance in anaerobic digestion, the dynamics of bacterial community structure
      was monitored with high-throughput sequencing in triplicate anaerobic digesters
      treating animal waste. Firmicutes and Bacteroidetes were found as the two most
      abundant populations, however, with contrasting population dynamics in response
      to organic overloading. Firmicutes dominated the bacterial community during
      stable process performance at low organic loading rate, representing over 50 % of
      the bacterial abundance. In contrast, the onset of organic overloading raised the
      relative abundance of Bacteroidetes from 20 +/- 2.6 to 44 +/- 3.1 %. In addition
      to the significant negative correlation between the relative abundance of
      Firmicutes and Bacteroidetes, populations of Firmicutes and Bacteroidetes were
      found to be linked to process parameters including organic loading rate, volatile
      fatty acids concentration, and methane production. Therefore, the population
      abundance ratio of Firmicutes to Bacteroidetes (F/B ratio) was suggested as a
      potential indicator for process performance. The interactions between Firmicutes
      and Bacteroidetes populations could be exploited to develop strategies for the
      prevention of performance perturbation in anaerobic digestion processes.

PMID- 27021845
TI  - Effect of the cathode potential and sulfate ions on nitrate reduction in a
      microbial electrochemical denitrification system.
AB  - Recently, bioelectrochemical systems have been demonstrated as advantageous for
      denitrification. Here, we investigated the nitrate reduction rate and bacterial
      community on cathodes at different cathode potentials [-300, -500, -700, and -900
      mV vs. standard hydrogen electrode (SHE)] in a two-chamber microbial
      electrochemical denitrification system and effects of sulfate, a common nitrate
      co-contaminant, on denitrification efficiency. The results indicated that the
      highest nitrate reduction rates (3.5 mg L(-1) days(-1)) were obtained at a
      cathode potential of -700 mV, regardless of sulfate presence, while a lower rate
      was observed at a more negative cathode potential (-900 mV). Notably, although
      sulfate ions generally inhibited nitrate reduction, this effect was absent at a
      cathode potential of -700 mV. Polymerase chain reaction-denaturing gradient gel
      electrophoresis revealed that bacterial communities on the graphite-felt cathode
      were significantly affected by the cathode potential change and sulfate presence.
      Shinella-like and Alicycliphilus-like bacterial species were exclusively observed
      on cathodes in reactors without sulfate. Ochrobactrum-like and Sinorhizobium-like
      bacterial species, which persisted at different cathode potentials irrespective
      of sulfate presence, were shown to contribute to bioelectrochemical
      denitrification. This study suggested that a cathode potential of around -700 mV
      versus SHE would ensure optimal nitrate reduction rate and counteract inhibitory
      effects of sulfate. Additionally, sulfate presence considerably affects
      denitrification efficiency and microbial community of microbial electrochemical
      denitrification systems.

PMID- 27021846
TI  - Intending to forget is not easy: Behavioral and electrophysiological evidence.
AB  - Previous researches have shown that recognition accuracy is lower for items cued
      to-be-forgotten (TBF) than to-be-remembered (TBR). Does directed forgetting help
      people forget more items than non-directed forgetting? Here, we modified the
      directed forgetting paradigm by adding a non-cue condition (NC). Consequently,
      non-directed forgetting would occur in NC. Behavioral results showed higher
      recognition accuracy for TBF than NC items, indicating that directed forgetting
      is less effective than non-directed forgetting. Electrophysiological results
      indicated that: (1) Remembered TBF items evoke an increased late positive
      component (LPC) than remembered NC items; (2) compared with remembered NC items,
      remembered TBF items showed a pronounced left-lateralized old/new effect and a
      reduced right-lateralized reversed old/new effect; (3) a right-lateralized
      reversed old/new effect was observed for forgotten TBF, but it was absent for
      forgotten NC items. These results demonstrate that the TBF items have a greater
      memory trace than the NC items. Forgetting cue has little effect of forgetting
      item from memory, and it might prompt subject to process or at least focus
      attention on the TBF items.

PMID- 27021847
TI  - Oxidative stress balance is dysregulated and represents an additional target for
      treating cholangiocarcinoma.
AB  - BACKGROUND: Pancreatico-biliary malignancies exhibit similar characteristics,
      including obesity-related features and poor prognosis, and require new treatment
      strategies. Oxidative stress is known to induce DNA damage and carcinogenesis,
      and its reduction is viewed as being favorable. However, it also has anti
      infection and anti-cancer functions that need to be maintained. To reveal the
      effect of oxidative stress on cancer progression, we evaluated oxidative stress
      and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC)
      patients, as well as the effect of add-on antioxidant treatment to chemotherapy
      in a mouse cholangiocarcinoma model. METHODS: We recruited 84 CC and 80 PC
      patients who were admitted to our hospital. Serum levels of reactive oxygen
      metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and
      the balance of these tests was defined as an oxidative index. A diabetic mouse
      based cholangiocarcinoma model was utilized to evaluate the effects of add-on
      antioxidant therapy on cholangiocarcinoma chemotherapy. RESULTS: Serum ROM was
      higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These
      parameters were not significantly different in PC patients. In mice, vitamin E
      administration induced antioxidant hemeoxygenase (HO)-1 protein expression in
      cancer tissue, while the number of stem-like cells increased. l-carnitine
      administration improved intestinal microbiome and biliary acid balance,
      upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non
      cancerous tissue, and did not alter stem-like cell numbers. CONCLUSION: Oxidative
      stress balance was dysregulated in cholangiocarcinoma with poor outcome. The
      mitochondrial function-supporting agent l-carnitine is a good candidate to
      control oxidative stress conditions.

PMID- 27021848
TI  - Cognitive Performance, Driving Behavior, and Attitudes over Time in Older Adults.
AB  - We hypothesized that changes over time in cognitive performance are associated
      with changes in driver perceptions, attitudes, and self-regulatory behaviors
      among older adults. Healthy older adults (n = 928) underwent cognitive
      assessments at baseline with two subsequent annual follow-ups, and completed
      scales regarding their perceptions, attitudes, and driving behaviours.
      Multivariate analysis showed small but statistically significant relationships
      between the cognitive tests and self-report measures, with the largest magnitudes
      between scores on the Trails B cognitive task (seconds), perceptions of driving
      abilities (beta = -0.32), and situational driving avoidance (beta = 0.55) (p <
      0.05). Cognitive slowing and executive dysfunction appear to be associated with
      modestly lower perceived driving abilities and more avoidance of driving
      situations over time in this exploratory analysis.

PMID- 27021849
TI  - Dual antiplatelet therapy after stroke or transient ischaemic attack - how long
      to treat? The duration of aspirin plus clopidogrel in stroke or transient
      ischaemic attack: a systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and
      clopidogrel for 90 days was recommended as the secondary prevention of minor
      ischaemic strokes or transient ischaemic attacks (TIAs) in 2014. However, whether
      the duration of 90 days is optimal for each patient remains unclear. Therefore,
      the efficacy and safety of short-term (<=3 months) and prolonged (>=1 year) DAPT
      after stroke or TIA were assessed via a systematic review and meta-analysis.
      METHODS: The Cochrane Library, Clinical Trials.gov and PubMed were searched up to
      December 2014 and nine randomized controlled trials were included involving 21
      923 patients. RESULTS: Short-term DAPT significantly reduced the risk of
      ischaemic stroke recurrence by 41% and major vascular events by 30%, without
      increasing the risk of intracranial haemorrhage. Prolonged DAPT reduced the risk
      of ischaemic stroke recurrence by 12% and major vascular events by 10%. However,
      the risk of major bleeding and intracranial haemorrhage increased. CONCLUSIONS:
      Short-term DAPT appears to be superior to prolonged DAPT. However, the difference
      in efficacy outcome needs to be carefully explained and confirmed by further well
      designed randomized controlled trials.

PMID- 27021850
TI  - Small molecule ice recrystallization inhibitors mitigate red blood cell lysis
      during freezing, transient warming and thawing.
AB  - During cryopreservation, ice recrystallization is a major cause of cellular
      damage. Conventional cryoprotectants such as dimethyl sulfoxide (DMSO) and
      glycerol function by a number of different mechanisms but do not mitigate or
      control ice recrystallization at concentrations utilized in cryopreservation
      procedures. In North America, cryopreservation of human red blood cells (RBCs)
      utilizes high concentrations of glycerol. RBC units frozen under these conditions
      must be subjected to a time-consuming deglycerolization process after thawing in
      order to remove the glycerol to <1% prior to transfusion thus limiting the use of
      frozen RBC units in emergency situations. We have identified several low
      molecular mass ice recrystallization inhibitors (IRIs) that are effective
      cryoprotectants for human RBCs, resulting in 70-80% intact RBCs using only 15%
      glycerol and slow freezing rates. These compounds are capable of reducing the
      average ice crystal size of extracellular ice relative to a 15% glycerol control
      validating the positive correlation between a reduction in ice crystal size and
      increased post-thaw recovery of RBCs. The most potent IRI from this study is also
      capable of protecting frozen RBCs against the large temperature fluctuations
      associated with transient warming. 

PMID- 27021851
TI  - Is there a difference in efficacy, safety, and cost-effectiveness between 3
      factor and 4-factor prothrombin complex concentrates among trauma patients on
      oral anticoagulants?
AB  - PURPOSE: The aim of this study was to compare the efficacy, safety, and cost
      effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) vs 4-factor
      prothrombin complex concentrate PCC (4F-PCC) in trauma patients requiring
      reversal of oral anticoagulants. MATERIALS AND METHODS: All consecutive trauma
      patients with coagulopathy (international normalized ratio [INR] >=1.5) secondary
      to oral anticoagulants who received either 3F-PCC or 4F-PCC from 2010 to 2014 at
      2 trauma centers were reviewed. Efficacy was determined by assessing the first
      INR post-PCC administration, and successful reversal was defined as INR less than
      1.5. Safety was assessed by reviewing thromboembolic events, and cost
      effectiveness was calculated using total treatment costs (drug acquisition plus
      transfusion costs) per successful reversal. RESULTS: Forty-six patients received
      3F-PCC, and 18 received 4F-PCC. Baseline INR was similar for 3F-PCC and 4F-PCC
      patients (3.1 +/- 2.3 vs 3.4 +/- 3.7, P = .520). The initial PCC dose was 29 +/-
      9 U/kg for 3F-PCC and 26 +/- 6 U/kg for 4F-PCC (P = .102). The follow-up INR was
      1.6 +/- 0.6 for 3F-PCC and 1.3 +/- 0.2 for 4F-PCC (P = .001). Successful reversal
      rates in patients were 83% for 4F-PCC and 50% for 3F-PCC (P = .022).
      Thromboembolic events were observed in 15% of patients with 3F-PCC vs 0% with 4F
      PCC (P = .177). Cost-effectiveness favored 4F-PCC ($5382 vs $3797). CONCLUSIONS:
      Three-factor PCC and 4F-PCC were both safe in correcting INR, but 4F-PCC was more
      effective, leading to better cost-effectiveness. Replacing 3F-PCC with 4F-PCC for
      urgent coagulopathy reversal may benefit patients and institutions.

PMID- 27021853
TI  - PSA ANNUAL MEETING 2011.

PMID- 27021852
TI  - Prognostic value of extravascular lung water and its potential role in guiding
      fluid therapy in septic shock after initial resuscitation.
AB  - PURPOSES: To explore whether extravascular lung water (EVLW) provides a valuable
      prognostic tool guiding fluid therapy in septic shock patients after initial
      resuscitation. MATERIALS AND METHODS: We performed a retrospective study of
      septic shock patients who achieved adequate initial fluid resuscitation with
      extended hemodynamic monitoring, analyzing the prognostic value of EVLW and
      whether fluid therapy for 24 (T24) or 24-48 hours (T24-48) after initial
      resuscitation with a recommended value of EVLW yielded a 28-day mortality
      advantage. RESULTS: One hundred five patients with septic shock were included in
      this study, 60 (57.1%) of whom died after 28 days. For 48 hours after initial
      resuscitation, the daily fluid balance (DFB; T24: 2494 +/- 1091 vs 1965 +/- 964
      mL [P = .011] and T24-48: 2127 +/- 783 vs 1588 +/- 665 mL [P < .001]) and daily
      maximum values of the EVLW index (EVLWImax; T24: 13.9 +/- 3.7 vs 11.5 +/- 3.2
      mL/kg [P < .001] and T24-48: 14.4 +/- 5.3 vs 12.0 +/- 4.4 mL/kg [P < .001]) were
      significantly higher in nonsurvivors than in survivors. In multivariate
      regression analysis, the DFB (T24: odds ratio [OR] 1.001 [P = .016] and T24-48:
      OR 1.001 [P = .008]), EVLWImax (T24: OR 2.158 [P = .002] and T24-48: OR 3.277 [P
      = .001]), blood lactate (T24: OR 1.368 [P = .021] and T24-48: OR 4.112 [P <
      .001]), and central venous blood oxygen saturation (T24: OR 0.893 [P = .013] and
      T24-48: OR 0.780 [P = .004]) were all independently associated with the 28-day
      mortality. A receiver operating characteristic analysis revealed that area under
      the curve values of 0.82 (95% confidence interval, 0.74-0.91; P < .001) and 0.90
      (95% confidence interval, 0.83-0.96; P < .001) for EVLWImax >= 12.5 mL/kg (T24
      and T24-48) predicted a 28-day mortality with sensitivities of 88% (80%-96%) and
      95% (90%-100%) and specificities of 60% (46%-74%) and 76% (63%-89%).The EVLWImax
      was correlated with DFB with Spearman rho values of 0.497 (T24: P < .001) and
      0.650 (T24-48: P < .001). Cox survival and regression analyses demonstrated that
      EVLWImax >= 12.5 mL/kg (T24 and T24-48) was associated with higher risk and
      increased mortality, with adjusted ORs of 4.77 (P < .001) and 10.86 (P < .001).
      CONCLUSIONS: A higher EVLW in septic shock patients after initial resuscitation
      was associated with a more positive fluid balance and increased mortality, which
      is an independent predictor of the 28-day mortality in septic shock patients
      after initial resuscitation.

PMID- 27021854
TI  - BIOACTIVE PROTEINS, PEPTIDES, AND AMINO ACIDS FROM MACROALGAE(1).
AB  - Macroalgae are a diverse group of marine organisms that have developed complex
      and unique metabolic pathways to ensure survival in highly competitive marine
      environments. As a result, these organisms have been targeted for mining of
      natural biologically active components. The exploration of marine organisms has
      revealed numerous bioactive compounds that are proteinaceous in nature. These
      include proteins, linear peptides, cyclic peptides and depsipeptides, peptide
      derivatives, amino acids, and amino acid-like components. Furthermore, some
      species of macroalgae have been shown to contain significant levels of protein.
      While some protein-derived bioactive peptides have been characterized from
      macroalgae, macroalgal proteins currently still represent good candidate raw
      materials for biofunctional peptide mining. This review will provide an overview
      of the important bioactive amino-acid-containing compounds that have been
      identified in macroalgae. Moreover, the potential of macroalgal proteins as
      substrates for the generation of biofunctional peptides for utilization as
      functional foods to provide specific health benefits will be discussed. 

PMID- 27021855
TI  - LIPOXYGENASE PRODUCTS IN MARINE DIATOMS: A CONCISE ANALYTICAL METHOD TO EXPLORE
      THE FUNCTIONAL POTENTIAL OF OXYLIPINS(1).
AB  - Oxylipins are oxygenated derivatives of polyunsaturated fatty acids (PUFAs) that
      act as chemical mediators in many ecological and physiological processes in
      marine and freshwater diatoms. The occurrence and distribution of these molecules
      are relatively widespread within the lineage with considerable species-specific
      differences due to the variability of both the fatty acids recognized as
      substrates and the enzymatic transformations. The present review provides a
      general introduction to recent studies on diatom oxylipins and describes an
      analytical method for the detection and assessment of these elusive molecules in
      laboratory and field samples. This methodology is based on selective enrichment
      of the oxylipin fraction by solvent extraction, followed by parallel acquisition
      of full-scan UV and tandem mass spectra on reverse phase liquid chromatography
      (LC) peaks. The analytical procedure enables identification of potential genetic
      differences, enzymatic regulation, and ecophysiological conditions that result in
      different oxylipin signatures, thus providing an effective tool for probing the
      functional relevance of this class of lipids in plankton communities. Examples of
      oxylipin measurements in field samples are also provided as a demonstration of
      the analytical potential of the methodology. 

PMID- 27021856
TI  - A MULTISPECIES LABORATORY ASSESSMENT OF RAPID SPOROPHYTE RECRUITMENT FROM DELAYED
      KELP GAMETOPHYTES(1).
AB  - Recent work suggests that the ability to delay reproduction as resistant haploid
      gametophytes may be important for seaweeds that experience unpredictable
      disturbances or seasonal periods of poor conditions that result in adult
      sporophyte absence. Further, delayed gametophytes of some kelp species (order
      Laminariales) may produce sporophytes more rapidly than if they had never
      experienced a delay, conferring a competitive advantage when conditions improve
      or after disturbance events. Here, it was determined that the gametophytes of the
      canopy-forming kelp Macrocystis pyrifera (L.) C. Agardh could delay reproduction
      in a one- to two-cell state (<50 MUm) for at least 7 months when grown under
      nutrient-limiting conditions. These stages retained reproductive viability and
      produced sporophytes within 5 d once nutrients were increased. This finding
      suggests that gametophytes could potentially promote recovery of M. pyrifera
      populations after extended periods of sporophyte absence. In addition, the time
      required for sporophyte production between gametophytes of the four most
      conspicuous kelp species in Southern California that had delayed reproduction and
      gametophytes that had not was compared. For these four kelp species, a delay of
      at least 30 d conferred a 40%-76% reduction in the time required for sporophyte
      production once nutrients were received. Fecundity did not decrease with delay
      duration, suggesting there is no apparent cost of delayed development for kelps
      as has been observed in other organisms. Thus, delayed development may be a
      viable strategy for surviving and initially dominating in environments with
      variable quality. 

PMID- 27021857
TI  - GRAZING ON GIANT KELP MICROSCOPIC PHASES AND THE RECRUITMENT SUCCESS OF ANNUAL
      POPULATIONS OF MACROCYSTIS PYRIFERA (LAMINARIALES, PHAEOPHYTA) IN SOUTHERN
      CHILE(1).
AB  - The giant kelp Macrocystis pyrifera (L.) C. Agardh is widely distributed in the
      Northern Hemisphere and Southern Hemisphere, yet it exhibits distinct population
      dynamics at local to regional spatial scales. Giant kelp populations are
      typically perennial with the potential for year-round reproduction and
      recruitment. In southern Chile, however, annual giant kelp populations exist and
      often persist entirely on secondary substrata (e.g., shells of the slipper limpet
      Crepipatella fecunda [Gastropoda, Calyptraeidae]) that can cover up to 90% of the
      rocky bottom. In these populations, the macroscopic sporophyte phase disappears
      annually during winter and early spring, leaving a 3-4 month period in which a
      persistent microscopic phase remains to support the subsequent year's
      recruitment. We tested the effects of a suite of grazers on the recruitment
      success of this critical microscopic phase at two sites in southern Chile. Field
      experiments indicated that the snail Tegula atra negatively impacted M. pyrifera
      sporophyte recruitment, but that recruitment was highest in the presence of
      sessile female limpets, C. fecunda. Conversely, small male C. fecunda (biofilm
      grazers) did not regulate kelp recruitment. Laboratory observations showed that
      C. fecunda males only grazed on microscopic kelp gametophytes and small (<250
      MUm) sporophytes, rejecting larger sporophytes, whereas T. atra grazed on all the
      kelp stages. Recruitment to the C. fecunda treatments far exceeded that to bare
      rock in the absence of grazers but was not due to the physical presence of C.
      fecunda shells. We concluded that the key to M. pyrifera recruitment success in
      southern Chile is its capacity to colonize secondary substrates provided by the
      slipper limpet C. fecunda. 

PMID- 27021858
TI  - MULTISCALE GENETIC STRUCTURE OF AN ENDANGERED SEAWEED AHNFELTIOPSIS PUSILLA
      (RHODOPHYTA): IMPLICATIONS FOR ITS CONSERVATION(1).
AB  - Although marine macroalgae have recently entered the lists of endangered species,
      conservation efforts are still limited by a lack of data, particularly for
      naturally rare species. One example is the turf-forming Ahnfeltiopsis pusilla
      (Mont.) P. C. Silva et DeCew. Albeit cataloged as vulnerable in the Northwest
      Iberian Peninsula (NWIP), where it occurs only at five enclaves separated by
      1,200 km from the closest recorded presence of the species, nothing is known
      about its genetic diversity and population connectivity. We used amplified
      fragment length polymorphism (AFLP) and sequences of the intergenic region
      between the mitochondrial cytochrome oxidase subunit 2 and subunit 3 genes (cox2
      3) to investigate its genetic structure at large (1,200 km), regional (<125 km),
      fine (<250 m), and patch (<1 m) scales. While cox2-3 variability was too low for
      the intraspecific study, AFLP revealed that most of the genetic diversity was due
      to differences between populations. Locally, genetic diversity was always low,
      and clones were frequent, suggesting that asexual reproduction may be common;
      patches of turf, however, often were composites of various genetic individuals.
      Genetic structure at local, regional, and large scales indicated that A. pusilla
      is a poor disperser, and an assignment test found no evidence of real-time
      dispersal between NWIP sites. Therefore, it is proposed that the five NWIP
      enclaves are designated independent management units (MUs). Bayesian-clustering
      approaches suggested that the three southernmost sites are particularly valuable
      for conservation since they concentrate most of the genetic heritage of A.
      pusilla in NWIP. Our study shows that the approaches of conservation genetics may
      provide useful insights for endangered seaweeds. 

PMID- 27021859
TI  - PHYSIOLOGICAL PERFORMANCE OF FLOATING GIANT KELP MACROCYSTIS PYRIFERA
      (PHAEOPHYCEAE): LATITUDINAL VARIABILITY IN THE EFFECTS OF TEMPERATURE AND
      GRAZING(1).
AB  - Rafts of Macrocystis pyrifera (L.) C. Agardh can act as an important dispersal
      vehicle for a multitude of organisms, but this mechanism requires prolonged
      persistence of floating kelps at the sea surface. When detached, kelps become
      transferred into higher temperature and irradiance regimes at the sea surface,
      which may negatively affect kelp physiology and thus their ability to persist for
      long periods after detachment. To examine the effect of water temperature and
      herbivory on the photosynthetic performance, pigment composition, carbonic
      anhydrase (CA) activity, and the nitrogen (N) and carbon (C) content of floating
      M. pyrifera, experiments were conducted at three sites (20 degrees  S, 30 degrees
      S, 40 degrees  S) along the Chilean Pacific coast. Sporophytes of M. pyrifera
      were maintained at three different temperatures (ambient, ambient - 4 degrees C,
      ambient + 4 degrees C) and in presence or absence of the amphipod Peramphithoe
      femorata for 14 d. CA activity decreased at 20 degrees  S and 30 degrees  S,
      where water temperatures and irradiances were highest. At both sites, pigment
      contents were substantially lower in the experimental algae than in the initial
      algae, an effect that was enhanced by grazers. Floating kelps at 20 degrees  S
      could not withstand water temperatures >24 degrees C and sank at day 5 of
      experimentation. Maximal quantum yield decreased at 20 degrees  S and 30 degrees 
      S but remained high at 40 degrees  S. It is concluded that environmental stress
      is low for kelps floating under moderate temperature and irradiance conditions
      (i.e., at 40 degrees  S), ensuring their physiological integrity at the sea
      surface and, consequently, a high dispersal potential for associated biota. 

PMID- 27021860
TI  - PHYLOGENETIC DIVERSITY OF TRENTEPOHLIALEAN ALGAE ASSOCIATED WITH LICHEN-FORMING
      FUNGI(1).
AB  - Nearly one-fourth of the lichen-forming fungi associate with trentepohlialean
      algae, yet their genetic diversity remains unknown. Recent work focusing on free
      living trentepohlialean algae has provided a phylogenetic context within which
      questions regarding the lichenization of these algae can be asked. Here, we
      concentrated our sampling on trentepohlialean algae from lichens producing a
      diversity of growth forms (fruticose and crustose) over a broad geographic
      substratum, ecological, and phylogenetic range. We have demonstrated that there
      is no evidence for a single clade of strictly lichenized algae; rather, a wide
      range demonstrated the ability to associate with lichenized fungi. Variation was
      also observed among trentepohlialean algae in lichens from a single geographic
      area and tree, suggesting that fungi in close proximity can associate with
      different trentepohlialean algae, consistent with the findings of
      trebouxiophycean algae and cyanobacteria. 

PMID- 27021861
TI  - CHANGES IN ENDOGENOUS CYTOKININ CONCENTRATIONS IN CHLORELLA (CHLOROPHYCEAE) IN
      RELATION TO LIGHT AND THE CELL CYCLE(1).
AB  - Endogenous cytokinins were quantified in synchronized Chlorella minutissima Fott
      et Novakova (MACC 361) and Chlorella sp. (MACC 458) grown in a 14:10 light:dark
      (L:D) photoperiod. In 24 h experiments, cell division occurred during the dark
      period, and cells increased in size during the light period. Cytokinin profiles
      were similar in both strains, consisting of five cis-zeatin (cZ) and three N(6) 
      (2-isopentenyl)adenine (iP) derivatives. Cytokinin concentrations were low during
      the dark period and increased during the light period. In 48 h experiments using
      synchronized C. minutissima (MACC 361), half the cultures were maintained in
      continuous dark conditions for the second photoperiod. Cell division occurred
      during both dark periods, and cells increased in size during the light periods.
      Cultures kept in continuous dark did not increase in size following cell
      division. DNA analysis confirmed these results, with cultures grown in light
      having increased DNA concentrations prior to cell division, while cultures
      maintained in continuous dark had less DNA. Cytokinins (cZ and iP derivatives)
      were detected in all samples with concentrations increasing over the first 24 h.
      This increase was followed by a large increase, especially during the second
      light period where cytokinin concentrations increased 4-fold. Cytokinin
      concentrations did not increase in cultures maintained in continuous dark
      conditions. In vivo deuterium-labeling technology was used to measure cytokinin
      biosynthetic rates during the dark and light periods in C. minutissima with
      highest biosynthetic rates measured during the light period. These results show
      that there is a relationship between light, cell division, and cytokinins. 

PMID- 27021862
TI  - EFFECT OF ZINC AVAILABILITY ON GROWTH, MORPHOLOGY, AND NUTRIENT INCORPORATION IN
      A COASTAL AND AN OCEANIC DIATOM(1).
AB  - We investigated the effect of Zn availability on growth rate (MU), cell
      morphology, and elemental stoichiometry and incorporation rate in two marine
      diatoms. For the coastal diatom Skeletonema costatum (Grev.) Cleve, the half
      saturation constant (KS ) for growth was 4.1 pM Zn(2+) , and growth ceased at <=
      2.6 pM Zn(2+) , whereas for the oceanic diatom Thalassiosira oceanica Hasle, KS
      was 0.5 pM Zn(2+) , and MU remained at ~40%MUmax even at 0.3 pM Zn(2+) . Under Zn
      limiting (Zn-L) conditions, S. costatum decreased cell size significantly,
      leading to an 80% increase in surface area to volume ratio (SA/V) at Zn(2+) of
      3.5 pM compared to Zn-replete (Zn-R) conditions (at Zn(2+) of 13.2 pM), whereas
      T. oceanica's morphology did not change appreciably. Cell quotas of C, N, P, Si,
      and chl a significantly decreased under Zn limitation in S. costatum (at Zn(2+)
      of 3.5 pM), whereas Zn limitation in T. oceanica (at Zn(2+) of 0.3 pM) had little
      effect on quotas. Elemental stoichiometry was ~85C:10N:9Si:1P and 81C:9N:5Si:1P
      for S. costatum, and 66C:5N:2Si:1P and 52C:6N:2Si:1P for T. oceanica, under Zn-R
      and Zn-L conditions, respectively. Incorporation rates of all elements were
      significantly reduced under Zn limitation for both diatoms, but particularly for
      Si in S. costatum, and for C in T. oceanica, despite its apparent tolerance of
      low Zn conditions. With [Zn(2+) ] in some parts of the ocean being of the same
      order (~0.2 to 2 pM) as our low Zn conditions for T. oceanica, our results
      support the hypothesis that in situ growth and C acquisition may be limited by Zn
      in some oceanic species. 

PMID- 27021863
TI  - ECOLOGICAL AND EVOLUTIONARY IMPLICATIONS OF CARBON ALLOCATION IN MARINE
      PHYTOPLANKTON AS A FUNCTION OF NITROGEN AVAILABILITY: A FOURIER TRANSFORM
      INFRARED SPECTROSCOPY APPROACH(1).
AB  - An imbalance in the cellular C:N ratio may appreciably affect C allocation in
      algal cells. The consequences of these rearrangements of cellular pools on cell
      energetics, ecological fitness, and evolutionary trajectories are little known,
      although they are expected to be substantial. We investigated the fate of C in 11
      microalgae cultured semicontinuously at three [NO3 (-) ] and constant pCO2 . We
      developed a new computational method for the semiquantitative use of Fourier
      transform infrared (FTIR) spectroscopy data for the determination of
      macromolecular composition. No obvious relationship was observed between the
      taxonomy and the allocation strategies adopted by the 11 species considered in
      this study. Not all species responded to a lower N availability by accumulating
      lipids or carbohydrates: Dunaliella parva W. Lerche and Thalassiosira pseudonana
      Hasle et Heimdal were homeostatic with respect to organic cell composition. A
      hyperbolic dependence of the lipid concentration from cell volume was observed.
      The level of reduction of organic constituents of green algae was parabolically
      related to size and was modulated in response to changes in N availability; the
      same was not true for the species bearing a "red" chloroplast. The above
      observations are discussed with respect to phytoplankton species composition and
      palatability for grazers, oleogenesis, and overall cell energetics. 

PMID- 27021864
TI  - PHOTOACCLIMATION IN THE PHOTOTROPHIC MARINE CILIATE MESODINIUM RUBRUM
      (CILIOPHORA)(1).
AB  - Mesodinium rubrum (=Myrionecta rubra), a marine ciliate, acquires plastids,
      mitochondria, and nuclei from cryptophyte algae. Using a strain of M. rubrum
      isolated from McMurdo Sound, Antarctica, we investigated the photoacclimation
      potential of this trophically unique organism at a range of low irradiance
      levels. The compensation growth irradiance for M. rubrum was 0.5 MUmol quanta .
      m(-2)  . s(-1) , and growth rate saturated at ~20 MUmol quanta . m(-2)  . s(-1) .
      The strain displayed trends in photosynthetic efficiency and pigment content
      characteristic of marine phototrophs. Maximum chl a-specific photosynthetic rates
      were an order of magnitude slower than temperate strains, while growth rates were
      half as large, suggesting that a thermal limit to enzyme kinetics produces a
      fundamental limit to cell function. M. rubrum acclimates to light- and
      temperature-limited polar conditions and closely regulates photosynthesis in its
      cryptophyte organelles. By acquiring and maintaining physiologically viable,
      plastic plastids, M. rubrum establishes a selective advantage over purely
      heterotrophic ciliates but reduces competition with other phototrophs by
      exploiting a very low-light niche. 

PMID- 27021865
TI  - AN OPTIMIZED METHOD FOR THE ISOLATION OF NUCLEI FROM CHLAMYDOMONAS REINHARDTII
      (CHLOROPHYCEAE)(1).
AB  - The cell nucleus harbors a large number of proteins involved in transcription,
      RNA processing, chromatin remodeling, nuclear signaling, and ribosome assembly.
      The nuclear genome of the model alga Chlamydomonas reinhardtii P. A. Dang. was
      recently sequenced, and many genes encoding nuclear proteins, including
      transcription factors and transcription regulators, have been identified through
      computational discovery tools. However, elucidating the specific biological roles
      of nuclear proteins will require support from biochemical and proteomics data.
      Cellular preparations with enriched nuclei are important to assist in such
      analyses. Here, we describe a simple protocol for the isolation of nuclei from
      Chlamydomonas, based on a commercially available kit. The modifications done in
      the original protocol mainly include alterations of the differential
      centrifugation parameters and detergent-based cell lysis. The nuclei-enriched
      fractions obtained with the optimized protocol show low contamination with
      mitochondrial and plastid proteins. The protocol can be concluded within only 3
      h, and the proteins extracted can be used for gel-based and non-gel-based
      proteomic approaches. 

PMID- 27021866
TI  - FLOW-INDUCED MORPHOLOGICAL VARIATIONS AFFECT DIFFUSION BOUNDARY-LAYER THICKNESS
      OF MACROCYSTIS PYRIFERA (HETEROKONTOPHYTA, LAMINARIALES)(1).
AB  - In slow mainstream flows (<4-6 cm . s(-1) ), the transport of dissolved nutrients
      to seaweed blade surfaces is reduced due to the formation of thicker diffusion
      boundary layers (DBLs). The blade morphology of Macrocystis pyrifera (L.) C.
      Agardh varies with the hydrodynamic environment in which it grows; wave-exposed
      blades are narrow and thick with small surface corrugations (1 mm tall), whereas
      wave-sheltered blades are wider and thinner with large (2-5 cm) edge undulations.
      Within the surface corrugations of wave-exposed blades, the DBL thickness,
      measured using an O2 micro-optode, ranged from 0.67 to 0.80 mm and did not vary
      with mainstream velocities between 0.8 and 4.5 cm . s(-1) . At the corrugation
      apex, DBL thickness decreased with increasing seawater velocity, from 0.4 mm at
      0.8 cm . s(-1) to being undetectable at 4.5 cm . s(-1) . Results show how the
      wave-exposed blades trap fluid within the corrugations at their surface. For wave
      sheltered blades at 0.8 cm . s(-1) , a DBL thickness of 0.73 +/- 0.31 mm within
      the edge undulation was 10-fold greater than at the undulation apex, while at 2.1
      cm . s(-1) , DBL thicknesses were similar at <0.07 mm. Relative turbulence
      intensity was measured using an acoustic Doppler velocimeter (ADV), and overall,
      there was little evidence to support our hypothesis that the edge undulations of
      wave-sheltered blades increased turbulence intensity compared to wave-exposed
      blades. We discuss the positive and negative effects of thick DBLs at seaweed
      surfaces. 

PMID- 27021867
TI  - SYSTEMATIC REVISION OF THE GENERA LIAGORA AND IZZIELLA (LIAGORACEAE, RHODOPHYTA)
      FROM TAIWAN BASED ON MOLECULAR ANALYSES AND CARPOSPOROPHYTE DEVELOPMENT, WITH THE
      DESCRIPTION OF TWO NEW SPECIES(1).
AB  - Some Liagora and Izziella distributed in Taiwan display a wide range of
      morphological variation and can be difficult to distinguish. To clarify species
      concepts, we applied DNA sequence analyses and examined carposporophyte
      development in detail. These studies revealed two new species, which are
      described herein as Izziella hommersandii sp. nov. and Izziella kuroshioensis sp.
      nov. I. kuroshioensis superficially resembles Izziella formosana and Izziella
      orientalis in that its involucral filaments subtend rather than surround the
      lower portion of the gonimoblast mass (= Izziella type) and a fusion cell is
      formed from cells of the carpogonial branch, but it can be separated by
      differences in the cell numbers and branching pattern of the involucral
      filaments, as well as thallus morphology. In contrast to other species that also
      bear short lateral branchlets, I. hommersandii is unique in possessing a mixture
      of short and long involucral filaments, a phenomenon not reported before. The
      length of the involucral filaments is species specific among species of Izziella
      and contrasts to the behavior of the involucral filaments after fertilization in
      species such as "Liagora"setchellii [= Titanophycus setchellii comb. nov.], in
      which the filaments completely envelop the gonimoblast. In addition, the cells of
      the carpogonial branch in Titanophycus do not fuse after fertilization to form a
      fusion cell. Thus, a combination of characters with respect to the behavior of
      the carpogonial branch and the involucral filaments after fertilization is very
      useful for delineating species boundaries in Izziella and for separating
      Titanophycus from Izziella and Liagora. 

PMID- 27021868
TI  - PHYLOGENETIC ANALYSIS OF BRACHIDINIUM CAPITATUM (DINOPHYCEAE) FROM THE GULF OF
      MEXICO INDICATES MEMBERSHIP IN THE KARENIACEAE(1).
AB  - Brachidinium capitatum F. J. R. Taylor, typically considered a rare oceanic
      dinoflagellate, and one which has not been cultured, was observed at elevated
      abundances (up to 65 cells . mL(-1) ) at a coastal station in the western Gulf of
      Mexico in the fall of 2007. Continuous data from the Imaging FlowCytobot (IFCB)
      provided cell images that documented the bloom during 3 weeks in early November.
      Guided by IFCB observations, field collection permitted phylogenetic analysis and
      evaluation of the relationship between Brachidinium and Karenia. Sequences from
      SSU, LSU, internal transcribed spacer (ITS), and cox1 regions for B. capitatum
      were compared with five other species of Karenia; all B. capitatum sequences were
      unique but supported its placement within the Kareniaceae. From a total of 71,487
      images, data on the timing and frequency of dividing cells was also obtained for
      B. capitatum, allowing the rate of division for B. capitatum to be estimated. The
      maximum daily growth rate estimate was 0.22 d(-1) . Images showed a range in
      morphological variability, with the position of the four major processes highly
      variable. The combination of morphological features similar to the genus Karenia
      and a phylogenetic analysis placing B. capitatum in the Karenia clade leads us to
      propose moving the genus Brachidinium into the Kareniaceae. However, the lack of
      agreement among individual gene phylogenies suggests that the inclusion of
      different genes and more members of the genus Karenia are necessary before a
      final determination regarding the validity of the genus Brachidinium can be made.

PMID- 27021869
TI  - BARRUFETA BRAVENSIS GEN. NOV. SP. NOV. (DINOPHYCEAE): A NEW BLOOM-FORMING SPECIES
      FROM THE NORTHWEST MEDITERRANEAN SEA(1).
AB  - The present study describes a new dinoflagellate genus, Barrufeta N. Sampedro et
      S. Fraga gen. nov., with one new species, B. bravensis Sampedro et S. Fraga sp.
      nov., isolated from the Costa Brava (NW Mediterranean Sea). The dinoflagellate
      was characterized at the genus and species levels by LM and EM; LSU and internal
      transcribed spacer (ITS) rDNA sequences; and HPLC analyses of the pigments, fatty
      acids, and possible presence of toxins of several cultured strains. The new
      Barrufeta species is oval shaped (22-35 MUm long and 16-25 MUm wide) and
      dorsoventrally flattened. It possesses numerous small chloroplasts that radiate
      from two large equatorially located pyrenoids and is a typical peridinin
      containing dinoflagellate. The nucleus is in the anterior part of the epicone.
      The apical groove has a characteristic "Smurf-cap" shape that runs
      counterclockwise on the epicone and terminates on its right posterior part. B.
      bravensis is similar to the previously described species Gyrodinium resplendens
      Hulburt in its external morphology, but the original report of the latter lacked
      a description of the complete shape of the apical groove. It is therefore likely
      that some of the G. resplendens species reported in the literature are Barrufeta
      since they possess a Barrufeta-type apical groove. Fatty acids of Barrufeta were
      more similar to those of Karenia brevis than those obtained from other unarmored
      analyzed species including three species of Gymnodinium and Akashiwo sanguinea. 

PMID- 27021870
TI  - MOLECULAR PHYLOGENY OF DINOPHYSOID DINOFLAGELLATES: THE SYSTEMATIC POSITION OF
      OXYPHYSIS OXYTOXOIDES AND THE DINOPHYSIS HASTATA GROUP (DINOPHYSALES,
      DINOPHYCEAE)(1).
AB  - The dinophysoid dinoflagellates are currently divided into three families:
      Amphisoleniaceae, Dinophysaceae (mainly Dinophysis Ehrenb. and Phalacroma F.
      Stein), and Oxyphysaceae, the latter including only one member, Oxyphysis
      oxytoxoides Kof. Phalacroma has been recently reinstated separately from
      Dinophysis, and its amended description is currently restricted to cells whose
      epithecae were large but <1/4 of the cell length. With the aim of improving the
      phylogeny of Dinophysales, we obtained 54 new SSU rRNA gene sequences of 28
      species. Taxon-rich SSU rDNA phylogenetic analysis showed that Dinophysales split
      into two major clades, one containing the Amphisoleniaceae (Amphisolenia F. Stein
      Triposolenia Kof.) and the other containing the Dinophysaceae. The latter are
      divided into two well-supported sister groups, the Dinophysaceae sensu stricto
      (s.s.) (Dinophysis, Ornithocercus F. Stein, Histioneis F. Stein) and,
      tentatively, a separate family for the clade of the type and most of the
      Phalacroma species. Based on combined phylogenies of new SSU rDNA and available
      LSU rDNA data, O. oxytoxoides (elongated epitheca, >1/4 of the cell length)
      branched with a strong support with the type of Phalacroma. We therefore propose
      Phalacroma oxytoxoides comb. nov. for O. oxytoxoides. Our SSU rDNA phylogeny also
      suggests that the assumed high intraspecific variability of Dinophysis hastata F.
      Stein hides a number of cryptic species. According to their distinct phylogenetic
      placement, the forms D. hastata f. phalacromides Jorg. and D. hastata f.
      uracanthides Jorg. should be erected at the species level. We propose for them
      the names Dinophysis phalacromoides comb. nov. and Dinophysis uracanthoides comb.
      nov. 

PMID- 27021871
TI  - EVOLUTIONARY ANALYSES OF THE NUCLEAR-ENCODED PHOTOSYNTHETIC GENE psbO FROM
      TERTIARY PLASTID-CONTAINING ALGAE IN DINOPHYTA(1).
AB  - Although the dinophytes generally possess red-algal-derived secondary plastids,
      tertiary plastids originating from haptophyte and diatom ancestors are recognized
      in some lineages within the Dinophyta. However, little is known about the nuclear
      encoded genes of plastid-targeted proteins from the dinophytes with diatom
      derived tertiary plastids. We analyzed the sequences of the nuclear psbO gene
      encoding oxygen-evolving enhancer protein from various algae with red-algal
      derived secondary and tertiary plastids. Based on our sequencing of 10 new genes
      and phylogenetic analysis of PsbO amino acid sequences from a wide taxon sampling
      of red algae and organisms with red-algal-derived plastids, dinophytes form three
      separate lineages: one composed of peridinin-containing species with secondary
      plastids, and the other two having haptophyte- or diatom-derived tertiary
      plastids and forming a robust monophyletic group with haptophytes and diatoms,
      respectively. Comparison of the N-terminal sequences of PsbO proteins suggests
      that psbO genes from a dinophyte with diatom-derived tertiary plastids
      (Kryptoperidinium) encode proteins that are targeted to the diatom plastid from
      the endosymbiotic diatom nucleus as in the secondary phototrophs, whereas the
      fucoxanthin-containing dinophytes (Karenia and Karlodinium) have evolved an
      additional system of psbO genes for targeting the PsbO proteins to their
      haptophyte-derived tertiary plastids from the host dinophyte nuclei. 

PMID- 27021872
TI  - STUDIES ON ULTRASTRUCTURE AND THREE-GENE PHYLOGENY OF THE GENUS MALLOMONAS
      (SYNUROPHYCEAE)(1).
AB  - The genus Mallomonas, a common and often abundant member of the planktic
      community in many freshwater habitats worldwide, consists of 180 species divided
      into 19 sections and 23 series. Classification of species is based largely on
      ultrastructural characteristics of the siliceous scales and bristles that
      collectively form a highly organized covering over the cell. However, the
      relative importance of the different siliceous features of the scales, such as
      the dome, V rib, and secondary structures, as well as the different types of
      scales, in understanding the evolution and phylogeny of the genus is little
      known. In this study, we investigated the scale and bristle ultrastructure, along
      with sequences of three genes, for 19 isolates (18 species) of Mallomonas (18
      isolates were from Korean habitats). The isolates represented nine of the 19
      sections. Sequences for both the nuclear SSU and LSU rDNA and plastid LSU of
      RUBISCO (rbcL) genes for each of the 19 Mallomonas isolates and four outgroups
      were determined. Bayesian and maximum-likelihood (ML) analyses of the data
      revealed that Mallomonas consists of two strongly supported clades. Mallomonas
      bangladeshica (E. Takah. et T. Hayak.) Siver et A. P. Wolfe was at the base of
      the first clade that included taxa from the sections Planae and Heterospinae,
      both of which lack a V rib on the shield of the scales. Our results indicated
      that the sections Planae and Heterospinae should be combined. The second clade,
      with Mallomonas insignis Penard and Mallomonas punctifera Korshikov at the base,
      contained taxa from the sections Mallomonas, Striatae, Akrokomae, Annulatae,
      Torquatae, Punctiferae, and Insignes, all of which have V ribs or well-developed
      marginal ribs on the scales. Sister relationships between Mallomonas and Striatae
      were strongly supported, but interrelations among the remaining sections were not
      resolved, probably due to inclusion of too few species. Our results suggest that
      the current classification of the genus Mallomonas at the section level will
      require some revision. Additional species will need to be added in future
      analyses. 

PMID- 27021873
TI  - DISCRIMINATIVE POWER OF NUCLEAR rDNA SEQUENCES FOR THE DNA TAXONOMY OF THE
      DINOFLAGELLATE GENUS PERIDINIUM (DINOPHYCEAE)(1).
AB  - The genus Peridinium Ehrenb. comprises a group of highly diversified
      dinoflagellates. Their morphological taxonomy has been established over the last
      century. Here, we examined relationships within the genus Peridinium, including
      Peridinium bipes F. Stein sensu lato, based on a molecular phylogeny derived from
      nuclear rDNA sequences. Extensive rDNA analyses of nine selected Peridinium
      species showed that intraspecies genetic variation was considerably low, but
      interspecies genetic divergence was high (>1.5% dissimilarity in the nearly
      complete 18S sequence; >4.4% in the 28S rDNA D1/D2). The 18S and 28S rDNA
      Bayesian tree topologies showed that Peridinium species grouped according to
      their taxonomic positions and certain morphological characters (e.g., epithecal
      plate formula). Of these groups, the quinquecorne group (plate formula of 3', 2a,
      7") diverged first, followed by the umbonatum group (4', 2a, 7") and polonicum
      group (4', 1a, 7"). Peridinium species with a plate formula of 4', 3a, 7"
      diverged last. Thus, 18S and 28S rDNA D1/D2 sequences are informative about
      relationships among Peridinium species. Statistical analyses revealed that the
      28S rDNA D1/D2 region had a significantly higher genetic divergence than the 18S
      rDNA region, suggesting that the former as DNA markers may be more suitable for
      sequence-based delimitation of Peridinium. The rDNA sequences had sufficient
      discriminative power to separate P. bipes f. occultaum (Er. Lindem.) M. Lefevre
      and P. bipes f. globosum Er. Lindem. into two distinct species, even though these
      taxa are morphologically only marginally discriminated by spines on antapical
      plates and the shape of red bodies during the generation of cysts. Our results
      suggest that 28S rDNA can be used for all Peridinium species to make species
      level taxonomic distinctions, allowing improved taxonomic classification of
      Peridinium. 

PMID- 27021874
TI  - Cepharanthine inhibits in vitro VSMC proliferation and migration and vascular
      inflammatory responses mediated by RAW264.7.
AB  - Pathogenesis of atherosclerosis involves vascular smooth muscle cell (VSMC)
      migration and proliferation followed by an inflammation mediated by activated
      macrophages in the tunica intima of blood vessels. Cepharanthine (CEP) belongs to
      bisbenzylisoquinoline alkaloids found in the plant Stephania cepharantha, which
      has been used for various diseases like cancer, alopecia areata, venomous
      snakebites, and malaria. In this study, we investigated whether CEP suppresses
      VSMC migration and proliferation and inhibits inflammatory mediator production in
      macrophage (RAW264.7). Our results showed that CEP possessed significant DPPH
      scavenging and metal chelating activities. It also markedly inhibited lipid
      peroxidation. Similarly, CEP suppressed the nitric oxide (NO) production and
      expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2)
      in RAW264.7 cells. Moreover, the level of prostaglandin E2 was also suppressed
      and the formation of macrophage derived foam cell was attenuated in RAW264.7
      cells. Likewise, NO production in isolated peritoneal macrophage and VSMC
      migration in response to LPS stimulated RAW264.7 was also halted by CEP
      treatment. Also, VSMC migration induced by platelet-derived growth factor (PDGF
      BB) was inhibited by CEP dose dependently. The anti-migratory effect of CEP on
      VSMCs was due to its inhibitory effect on metalloproteinase-9 (MMP-9) expression,
      preventing the degradation of extracellular matrix (ECM) component. Furthermore,
      CEP suppressed PDGF-BB induced VSMC proliferation by down-regulation of mitogen
      activated protein kinase (MAPK) signaling molecules. CEP also inhibited the
      translocation of NF-kappaB from cytosol to nucleus. Thus, our results suggest
      that CEP exerts potent anti-atherosclerotic effect through attenuation of
      inflammation, lipid peroxidation and VSMC migration and proliferation. 

PMID- 27021875
TI  - Pickering emulsions for skin decontamination.
AB  - This study aimed at developing innovative systems for skin decontamination.
      Pickering emulsions, i.e. solid-stabilized emulsions, containing silica (S-PE) or
      Fuller's earth (FE-PE) were formulated. Their efficiency for skin decontamination
      was evaluated, in vitro, 45min after an exposure to VX, one of the most highly
      toxic chemical warfare agents. Pickering emulsions were compared to FE (FE-W) and
      silica (S-W) aqueous suspensions. PE containing an oil with a similar
      hydrophobicity to VX should promote its extraction. All the formulations reduced
      significantly the amount of VX quantified on and into the skin compared to the
      control. Wiping the skin surface with a pad already allowed removing more than
      half of VX. FE-W was the less efficient (85% of VX removed). The other
      formulations (FE-PE, S-PE and S-W) resulted in more than 90% of the quantity of
      VX removed. The charge of particles was the most influential factor. The low pH
      of formulations containing silica favored electrostatic interactions of VX with
      particles explaining the better elimination from the skin surface. Formulations
      containing FE had basic pH, and weak interactions with VX did not improve the
      skin decontamination. However, these low interactions between VX and FE promote
      the transfer of VX into the oil droplets in the FE-PE. 

PMID- 27021876
TI  - Chebulic acid prevents hepatic fibrosis induced by advanced glycation end
      products in LX-2 cell by modulating Nrf2 translocation via ERK pathway.
AB  - Advanced glycation end-products (AGEs) are formed during normal aging, and at an
      accelerated rate in metabolic syndrome patients. Nonalcoholic steatohepatitis
      (NASH) can be caused by the AGEs in plasma, while glyceraldehyde-derived AGEs
      (glycer-AGEs) are significantly higher in the serum of NASH patients. In this
      study, we investigated the molecular mechanisms of chebulic acid, isolated from
      Terminalia chebula Retz., in the inhibition of glycer-AGEs induced production of
      reactive oxygen species (ROS) and collagen accumulation using the LX-2 cell line.
      Chebulic acid significantly inhibited the induction of ROS and accumulation of
      collagen proteins by glycer-AGEs. ERK phosphorylation and total nuclear factor E2
      related factor 2 (Nrf2) protein expression were induced by chebulic acid in a
      dose-dependent manner. Chebulic acid was also found to induce translocation of
      Nrf2 into the nucleus, which was attenuated by inhibition of ERK phosphorylation
      through treatment with PD98059. Following translocation of Nrf2, chebulic acid
      induced the protein expressions of catalytic subunit of gamma-glutamylcysteine
      synthetase and glutathione synthesis. Collagen accumulation was also
      significantly reduced by chebulic acid treatment. The observed effects of
      chebulic acid were all inhibited by PD98059 treatment. Taken together, these
      results suggest that chebulic acid prevents the glycer-AGEs-induced ROS formation
      of LX-2 cells and collagen accumulation by ERK-phosphorylation-mediated Nrf2
      nuclear translocation, which causes upregulation of antioxidant protein
      production. 

PMID- 27021878
TI  - Role of Actin Cytoskeleton in the Regulation of Epithelial Cutaneous Stem Cells.
AB  - Cutaneous stem cells (CSCs) orchestrate the homeostasis and regeneration of
      mammalian skin. Epithelial CSCs have been isolated and characterized from the
      skin and hold great potential for tissue engineering and clinical applications.
      The actin cytoskeleton is known to regulate cell adhesion and motility through
      its intricate participation in signal transduction and structural modifications.
      The dynamics of actin cytoskeleton can directly influence CSCs behaviors
      including tissue morphogenesis, homeostasis, niche maintenance, activation, and
      wound repair. Various regulators of the actin cytoskeleton including kinases,
      actin-remodeling proteins, paracrine signals, and micro-RNAs collaborate and
      contribute to epithelial CSC proliferation, adhesion, and differentiation. This
      review brings together the latest mechanistic insights into how the actin
      cytoskeleton participates in the regulation of epithelial CSCs during
      development, homeostasis, and wound repair.

PMID- 27021877
TI  - Hyperglycemia Suppresses Calcium Phosphate-Induced Aneurysm Formation Through
      Inhibition of Macrophage Activation.
AB  - BACKGROUND: The aim of this study was to elucidate aspects of diabetes mellitus
      induced suppression of aneurysm. We hypothesized that high glucose suppresses
      aneurysm by inhibiting macrophage activation via activation of Nr1h2 (also known
      as liver X receptor beta), recently characterized as a glucose-sensing nuclear
      receptor. METHODS AND RESULTS: Calcium phosphate (CaPO4)-induced aneurysm
      formation was significantly suppressed in the arterial wall in type 1 and 2
      diabetic mice. A murine macrophage cell line, RAW264.7, was treated with tumor
      necrosis factor alpha (TNF-alpha) plus CaPO4 and showed a significant increase in
      matrix metalloproteinase 9 (Mmp9) mRNA and secreted protein expression compared
      with TNF-alpha alone. Elevated Mmp9 expression was significantly suppressed by
      hyperglycemic conditions (15.5 mmol/L glucose) compared with normoglycemic
      conditions (5.5 mmol/L glucose) or normoglycemic conditions with high osmotic
      pressure (5.5 mmol/L glucose +10.0 mmol/L mannitol). Nr1h2 mRNA and protein
      expression were suppressed by treatment with TNF-alpha plus CaPO4 but were
      restored by hyperglycemic conditions. Activation of Nr1h2 by the antagonist
      GW3965 during stimulation with TNF-alpha plus CaPO4 mimicked hyperglycemic
      conditions and inhibited Mmp9 upregulation, whereas the deactivation of Nr1h2 by
      small interfering RNA (siRNA) under hyperglycemic conditions canceled the
      suppressive effect and restored Mmp9 expression induced by TNF-alpha plus CaPO4.
      Moreover, Nr1h2 activation with GW3965 significantly suppressed CaPO4-induced
      aneurysm in mice compared with vehicle-injected control mice. CONCLUSIONS: Our
      results show that hyperglycemia suppresses macrophage activation and aneurysmal
      degeneration through the activation of Nr1h2. Although further validation of the
      underlying pathway is necessary, targeting Nr1h2 is a potential therapeutic
      approach to treating aneurysm.

PMID- 27021879
TI  - [Assessment of daily quality of life in children surviving cancer].
AB  - INTRODUCTION: The purpose of this study was to identify the daily problems
      experienced by school-age children in remission from cancer. It also sought to
      assess the predictive value of these problems on the mental health of these
      children 1 year after the first assessment. PATIENTS AND METHOD: Against this
      background, 50 children in remission from cancer and in mainstream education,
      aged 8-12 years, completed two questionnaires: the Quality of Life Systemic
      Inventory for Children (QLSI-C) (Missotten et al., 2007) and the Child Depression
      Inventory (CDI). THE QLSI-C consists of 20 life areas: Sleep, Diet, Physical
      pain, Health, Clothing, Physical appearance, Bedroom, Grandparents, Mother,
      Father, Siblings, Friends, How my friends talk about me, School, School results,
      Sport, Non-sporting activities, Autonomy, Obedience to authority, and Tolerance
      of frustration. Each of these 20 life areas was evaluated by the child by
      reference on each occasion to an ideal situation, first in relation to their
      current situation and then in relation to their personal goals, in order to
      measure the gap between these two evaluations. This difference was then weighted
      by the importance given to each life area and the dynamic situation of
      approximation to or distance from the goals. All the children in this study were
      seen in person for two interviews 1 year apart (T1 and T2). RESULTS: The analyses
      conducted following the PLS-PM approach enabled eight of the 20 life areas
      evaluated to be identified as difficult to access by the children in this study.
      These analyses also showed that the difficulties perceived by children in
      remission from cancer have mainly proximal effects (i.e., short-term) on the
      discomfort experienced (direct effect of difficulties expressed in T1 on
      discomfort felt at T1; idem for T2). However, the areas perceived as difficult at
      T1 did not enable distal effects (i.e., effect over a year) on the discomfort
      expressed in T2 to be updated. Nonetheless, the conflicts at T1 fed the conflicts
      at T2 and, as a consequence, indirectly affected the experience of depression at
      T2. DISCUSSION: The discussion examines the nature of the daily difficulties
      perceived by school-age children in remission from cancer and the short-term
      psychological distress experienced by these children. It concludes that the
      difficulties encountered by children in remission from cancer are not necessarily
      cumulative over time and that they do not inevitably result in permanent
      psychological suffering.

PMID- 27021880
TI  - [Duplication of the gallbladder with heterotopic mucosa: A case report and
      proposal for a classification for gastrointestinal duplications].
AB  - BACKGROUND: Gastrointestinal duplications are rare congenital malformations that
      can occur anywhere between the mouth and the anus, including the digestive
      annexes. Numerous classifications of these malformations exist, varying from one
      author to another. This study describes a rare case of gallbladder duplication
      and suggests a unified classification of gastrointestinal duplications in order
      to merge epidemiological and clinical considerations. CASE REPORT: A 13-year-old
      boy presented with acute abdominal pain. Investigations revealed a cystic
      structure located in the gallbladder combined with lithiasis. Following an
      elective laparoscopic cholecystectomy, the diagnosis of gallbladder duplication
      in association with heterotopic gastrointestinal mucosa and pancreatic micro
      clusters was made. The patient is in excellent health 4 years after surgery.
      COMMENTARY AND CONCLUSION: This atypical duplication is rare and can most likely
      be explained by the proximity between the pancreas and gastrointestinal tract
      during their development: the intestinal metaplasia and the development of the
      gastric mucosa may further represent congenital lesions due to aberrant migration
      of normal tissue, or could be secondary to a chronic inflammatory response in the
      gallbladder. The revised standardized classification we propose is based on the
      accurate identification, precise location and detailed histology of the lesions.

PMID- 27021881
TI  - [Particularities of liver abscesses in children in Senegal: Description of a
      series of 26 cases].
AB  - Liver abscess is a serious infection that can cause life-threatening
      complications. OBJECTIVE: To describe the epidemiology, diagnosis, and
      progression of liver abscess at the Dakar National Albert-Royer Children's
      Hospital. METHOD: A retrospective study was conducted from over a period of 5
      years (1st January 2010 to 31st December 2014). All children aged 0-15 years
      hospitalized for liver abscess with ultrasound confirmation were included. We
      collected demographic data (age, gender, socioeconomic status, origin), clinical
      data (general and hepatic symptoms), diagnostic data (ultrasound, bacteriology)
      and progression (death, complications, sequelae). The data were analyzed with Epi
      info (P<0.05 was considered significant). RESULTS: We collected 26 cases of liver
      abscesses, representing a hospital prevalence of 100 cases per 100,000
      admissions. Males predominated (sex ratio: 1.36). The children's average age was
      7.2 years. Most of the children came from urban areas of Dakar. Low socioeconomic
      status and precarious lifestyle were the contributing factors. Anemia (69.2%),
      malnutrition (42.3%), and abdominal trauma (15.3%) were the main causes found.
      The Fontan triad characteristic of the liver abscess was found in 57.7% of cases.
      At ultrasound, a single abscess was found in 21 cases. The abscess was located in
      the right lobe in 18 cases, the left lobe in three cases, and in both lobes in
      three cases. Segment VI (four cases) was the most frequently involved.
      Bacteriologically, the abscess was pyogenic in 17 cases and an amoebic abscess in
      nine cases. The main pyogenic sources found were Klebsiella pneumoniae in two
      cases, Pseudomonas aeruginosa in one case, Streptococcus pneumoniae in one case,
      and Staphylococcus aureus in one case. The average duration of antibiotic
      treatment was 14.5 days. Liver drainage was carried out in 24 cases. The outcome
      was favorable in all children. CONCLUSION: The prevalence of liver abscesses at
      the Albert-Royer Children's Hospital is relatively high, compared to the
      literature data. Percutaneous drainage combined with antibiotics remains the
      treatment of choice. The prognosis is favorable.

PMID- 27021882
TI  - [Alcohol use in children: An unrecognized fact].
AB  - Although drinking problems are now well documented in adolescents and young
      people, few data are available on alcohol use in children younger than 12. In
      France, studies have shown that 60-70% of 11-year-olds reported having tasted
      alcohol drinks, 4-7% having experienced drunkenness at least once, and that 5-8%
      might be regarded as "regular" alcohol users. By comparison, the prevalence of
      child drinking in the United States seems to be lower. All studies show that
      parental alcohol-specific attitudes and parental educational practices have a
      strong influence on the initiation of alcohol use in children. Some of them also
      indicate that early-onset drinking in children may be related to psychosocial
      functioning in other life areas, such as problem behaviors, low school
      engagement, and poor relationships with parents, in association with
      temperamental and environmental risk factors similar to those described in
      substance use disorders. Since epidemiological studies showed that early
      initiation of alcohol use is linked to later alcohol-related problems, these data
      call for further attention to children's perceptions and attitudes with respect
      to alcohol in research to prevent alcohol misuse. 

PMID- 27021883
TI  - [Chronic interstitial lung disease in children: Diagnostic approach and
      management].
AB  - Chronic interstitial lung disease (ILD) in children is a heterogeneous group of
      rare lung disorders characterized by an inflammatory process of the alveolar wall
      and the pulmonary interstitium that induces gas exchange disorders. The
      diagnostic approach to an ILD involves three essential steps: recognizing the
      ILD, appreciating the impact, and identifying the cause. The spectrum of clinical
      findings depends to a large extent on age. In the newborn, the beginning is often
      abrupt (neonatal respiratory distress), whereas there is a more gradual onset in
      infants (failure to thrive, tachypnea, indrawing of the respiratory muscles). In
      older children, the onset is insidious and the diagnosis can only be made at an
      advanced stage of the disease. The diagnosis is based on noninvasive methods
      (clinical history, respiratory function tests, chest X-ray, and high-resolution
      CT scan) and invasive techniques (bronchoalveolar lavage, transbronchial biopsy,
      video-assisted thoracoscopic biopsy, and open lung biopsy). The treatment of
      interstitial lung disease in children depends on the nature of the underlying
      pathology. The most common therapeutic approach involves the use of
      corticosteroids and immunosuppressive agents for their anti-inflammatory and
      antifibrotic effects. Children with ILD also need support therapy (oxygen
      therapy, nutritional support, treatment of pulmonary arterial hypertension,
      vaccination). Lung transplantation is discussed in patients with severe
      respiratory failure. 

PMID- 27021884
TI  - [Hypercalcemia revealing sarcoidosis in a child].
AB  - Sarcoidosis is a systemic granulomatosis disease with a classic triad of
      presentation: typical clinical and radiological signs, presence of tuberculoid
      granuloma without caseum in histopathology, and exclusion of other causes of
      granulomatosis, especially tuberculosis. Sarcoidosis is rare in the general
      population, and even more so in children. In the literature, few cases of
      sarcoidosis associated with hypercalcemia have been reported in children. We
      report here the case of a 14-year-old boy with bone marrow and lymph node
      sarcoidosis suspected, based on poor general condition with hypercalcemia. The
      patient was treated with hydration, diuretics, and bisphosphonates with good
      results. We also performed a literature review of published cases of
      hypercalcemia since 1990 with a diagnosis of sarcoidosis in children, comparing
      23 cases (including ours) on clinical and epidemiological, biological, imaging,
      and histopathological diagnosis. When hypercalcemia is present in the initial
      clinical presentation, the diagnosis of sarcoidosis is usually made in younger
      children. Classical locations of the lesions, including lung, skin, and lymph
      nodes, were highly suggestive of sarcoidosis. Corticosteroids are commonly used
      to treat sarcoidosis lesions including hypercalcemia. In conclusion, sarcoidosis
      in children remains difficult to diagnose because the disease is rare and it is
      common to have nonspecific symptoms in the clinical picture (with diagnosis
      delayed between 3 months and several years). The classic triad is not always
      present. Sarcoidosis should be systematically considered and investigated in case
      of hypercalcemia of unknown cause in children. 

PMID- 27021885
TI  - Use of Doppler ultrasound in the management of uteroplacental perfusion during
      cardiopulmonary bypass in pregnancy.
AB  - Cardiopulmonary bypass, the extreme of non-obstetric surgery during pregnancy,
      presents unique challenges to minimize maternal and fetal risk. We present our
      experience with a woman who was diagnosed with a left atrial myxoma following an
      ischemic cerebrovascular accident. We discuss clinical management specific to
      cardiopulmonary bypass during pregnancy and delivery in the context of a
      multidisciplinary team approach. We recommend using intermittent Doppler
      ultrasound as a non-invasive real-time assessment of uteroplacental perfusion
      during non-obstetric surgery in pregnancy. Monitoring of perfusion facilitates
      active feedback for appropriate in utero resuscitation in these cases. 

PMID- 27021886
TI  - Effect of the head-elevation pillow on intrathecal local anaesthetic spread.

PMID- 27021888
TI  - Views on equine-related research in Australia from the Australian equestrian
      community: perceived outputs and benefits.
AB  - OBJECTIVES: The extension of research into public practice is enhanced by
      communication and behaviour change strategies that are consistent with consumer
      needs and perspectives. To gain support for equine research (or to appreciate the
      perspectives contributing to disagreement), it is necessary to determine how
      aware consumers are of research, what research means to them, how they perceive
      its benefits (if at all) and how they engage with (or resist) it. Because of a
      surprising dearth of research evaluating consumer perceptions of research in any
      sector, our aim was to identify the perceived outputs and benefits of research
      from the perspective of the Australian horse owner. METHODS: We analysed the data
      for 930 participants in an online survey. RESULTS: Participants' understanding of
      research was associated with a broad terminology. Slightly more than half were
      aware of equine research that had taken place in Australia, with almost half
      reporting gaining some benefit, notably in relation to equine health. Although
      comments demonstrated an awareness of the collective benefit of research,
      research was made meaningful in relation to local conditions and participants'
      own equestrian disciplines. CONCLUSION: There is a significant opportunity for
      increasing awareness of Australia-based equine research and its value to owners
      of horses. The critical engagement with research by some owners suggests the need
      for communicators to present research in terms suitable for an intelligent lay
      audience, with clear identification of the personal and collective benefits for
      owners, horses and the equestrian community.

PMID- 27021889
TI  - Artis Medenis 1920-2015.

PMID- 27021890
TI  - Pacemaker lead perforation of the right ventricle associated with Moraxella
      phenylpyruvica infection in a dog.
AB  - CASE DESCRIPTION: A 13-year-old neutered male Border Collie was presented with
      acute onset syncope, weakness and anorexia 10 months after transvenous pacemaker
      implantation. The patient was laterally recumbent, bradycardic (36 beats/min) and
      febrile (40.7 degrees C) on presentation. An electrocardiogram (ECG) revealed
      recurrence of third-degree atrioventricular block with a ventricular escape
      rhythm. Fluoroscopy identified migration of the pacemaker tip through the apex of
      the right ventricle. Echocardiography failed to reveal any evidence of
      pericardial effusion or cardiac tamponade. Full postmortem was performed after
      euthanasia. The pacemaker lead had perforated the apex of the right ventricle and
      lodged in the right pleural space. Culture of blood (taken antemortem),
      pericardial sac, right ventricular wall (surrounding pacemaker lead), pacemaker
      lead tip and pericardial fluid revealed a pure growth of Moraxella
      phenylpyruvica. CONCLUSION: Bacteraemia associated with M. phenylpyruvica has
      never been reported in the dog, but sporadic cases are reported in humans.
      Infection could have resulted from either pre-existing myocarditis or
      opportunistic infection and bacteraemia post pacemaker implantation. Evaluation
      of the pacemaker function at regular intervals would allow early detection of
      poor pacemaker-to-myocardium contact, which would prompt further investigation of
      pacemaker lead abnormalities such as perforation.

PMID- 27021891
TI  - Lissencephaly in an adult Australian Kelpie.
AB  - CASE REPORT: A 6-year-old neutered male Australian Kelpie presented with a 2-year
      history of seizures. Neurological examination was consistent with a generalised
      prosencephalic lesion. Serum biochemical testing was performed in addition to
      magnetic resonance imaging of the brain and cerebrospinal fluid analysis.
      Magnetic resonance imaging revealed a reduction in the number of sulci and gyri
      in addition to cortical thickening, resulting in a diagnosis of lissencephaly.
      The dog was treated with anticonvulsants and follow-up information obtained from
      the referring veterinarian 11 months after diagnosis indicated that the dog had
      good seizure control. CONCLUSION: This is the first report of lissencephaly in
      the Australian Kelpie and would suggest that some dogs with the condition can be
      managed with long-term anticonvulsant medication.

PMID- 27021892
TI  - Rigid removable cover for dorsal wound protection and tube fixation in pigs.
AB  - OBJECTIVE: To report the design and benefits of a rigid polyethylene cover
      'shell' for the protection of dorsal torso wounds and tube fixation in pigs.
      METHODS: Open C-shaped polyethylene shells were designed to protect wounds and
      dressings on the dorsum of pigs used in research into negative pressure dressing
      assisted wound healing. The shells were designed to resist trauma and
      contamination, to be comfortable and expansible, and to facilitate tube fixation
      and management. Strap fixation was optimised during experimentation. Efficacy was
      assessed by direct observation of dressing and wound protection, tube integrity
      and by macroscopic and microscopic assessments of wound healing. RESULTS: The
      shells effectively protected the wounds against blunt and sharp trauma, were
      simple to remove and reapply, were well tolerated and allowed for growth of the
      pigs. Circumferential neck straps attached by lateral straps to the shells proved
      critical. There was no wound infection or inflammation underlying the shells.
      Porting tubing via mid-dorsal holes in the shells and affixing the tubing just
      cranial to these holes prevented tube damage and traction, permitted tube
      management from outside the cages and allowed the pigs to move freely without
      becoming entangled. CONCLUSION: These shells effectively protected dorsal skin
      wounds and dressings, prevented tube damage and facilitated tube management in
      pigs. Similar systems may be useful for other production animals for wound
      management and for tube management with negative pressure wound healing, drain
      tubes or the delivery of nutrition, fluids or medications.

PMID- 27021893
TI  - Prevalence of Theileria orientalis types in beef cattle herds on the North Coast
      of New South Wales.
AB  - OBJECTIVE: To estimate the prevalence of Theileria orientalis infection for
      Chitose, Ikeda and Buffeli major piroplasm surface protein (MPSP) types at a herd
      and animal-level in beef cattle in the North Coast Livestock Health and Pest
      Authority (NCLHPA) region of New South Wales (NSW). METHODS: A total of 24 beef
      herds in the NCLHPA region containing more than 100 cattle were randomly
      selected. Blood samples were collected from five animals per herd and tested
      using Theileria PCR for Chitose, Buffeli and Ikeda. Samples were only taken from
      female cattle older than 2 years, born in the NCLHPA region and apparently
      healthy at the time of testing. RESULTS: The herd-level prevalence for all MPSP
      types (Chitose, Ikeda and Buffeli) was 100%, with a 95% confidence interval of
      86.3-99.9%. The mean prevalence at an animal level was 83.3%, 92.5% and 95.0% for
      Theileria Chitose, Buffeli and Ikeda, respectively. Quantitative PCR testing
      showed that 81.9% of animals had a low-level infection, while 17.0% had a
      moderate level of infection, and only 1.0% had a high level of infection. The
      majority of animals had a mixed infection of two or three MPSP types and few
      animals showed single infection. CONCLUSION: The results indicate endemicity of
      T. orientalis, especially the Ikeda type, in the NCLHPA region of Australia.

PMID- 27021894
TI  - Morbidity and mortality of monotremes admitted to the Australian Wildlife Health
      Centre, Healesville Sanctuary, Australia, 2000-2014.
AB  - OBJECTIVE: The medical records of individual monotremes admitted to the
      Australian Wildlife Health Centre from 2000 to 2014 were reviewed to determine
      the causes of morbidity and mortality. RESULTS: During this period, a total of 38
      platypus (Ornithorhyncus anatanus) and 273 short-beaked echidnas (Tachyglossus
      aculeatus) were examined. Trauma was the most significant reason for monotreme
      admissions, accounting for 73.7% of platypus cases and 90.1% of short-beaked
      echidna cases. Within the category of trauma, entanglement (28.6%) and unknown
      trauma (28.6%) were most significant for platypus, while impact with motor
      vehicle (73.2%) and domestic dog attack (14.2%) were the most significant
      subcategories for short-beaked echidnas. CONCLUSION: Indirect anthropogenic
      factors are a significant cause of morbidity and mortality of monotremes in
      Victoria, Australia.

PMID- 27021895
TI  - Cross-sectional observational survey of serum biochemistry values in a population
      of 69 adult female alpacas (Vicugna pacos) in South Australia.
AB  - Blood samples were collected from 69 'healthy' female alpacas aged >=12 months
      from 11 properties in South Australia. The 10-90 percentile ranges of the 16/19
      analytes measured in this sample population were within the published ranges of
      four healthy alpaca populations from other geographic locations. Marginal
      exceptions were glutamate dehydrogenase and bicarbonate. Potassium was notably
      elevated, probably because of haemolysis of some samples. The sample size was
      insufficient to provide the appropriate statistical power to define diagnostic
      references ranges according to international standards. The health status of the
      sample population of alpacas was presumptive based on a physical examination. 

PMID- 27021897
TI  - Synchronous slowing down in coupled logistic maps via random network topology.
AB  - The speed and paths of synchronization play a key role in the function of a
      system, which has not received enough attention up to now. In this work, we study
      the synchronization process of coupled logistic maps that reveals the common
      features of low-dimensional dissipative systems. A slowing down of
      synchronization process is observed, which is a novel phenomenon. The result
      shows that there are two typical kinds of transient process before the system
      reaches complete synchronization, which is demonstrated by both the coupled
      multiple-period maps and the coupled multiple-band chaotic maps. When the
      coupling is weak, the evolution of the system is governed mainly by the local
      dynamic, i.e., the node states are attracted by the stable orbits or chaotic
      attractors of the single map and evolve toward the synchronized orbit in a less
      coherent way. When the coupling is strong, the node states evolve in a high
      coherent way toward the stable orbit on the synchronized manifold, where the
      collective dynamics dominates the evolution. In a mediate coupling strength, the
      interplay between the two paths is responsible for the slowing down. The
      existence of different synchronization paths is also proven by the finite-time
      Lyapunov exponent and its distribution. 

PMID- 27021898
TI  - Three steps to gold: mechanism of protein adsorption revealed by Brownian and
      molecular dynamics simulations.
AB  - The addition of three N-terminal histidines to beta-lactamase inhibitor protein
      was shown experimentally to increase its binding potency to an Au(111) surface
      substantially but the binding mechanism was not resolved. Here, we propose a
      complete adsorption mechanism for this fusion protein by means of a multi-scale
      simulation approach and free energy calculations. We find that adsorption is a
      three-step process: (i) recognition of the surface predominantly by the histidine
      fusion peptide and formation of an encounter complex facilitated by a reduced
      dielectric screening of water in the interfacial region, (ii) adsorption of the
      protein on the surface and adoption of a specific binding orientation, and (iii)
      adaptation of the protein structure on the metal surface accompanied by induced
      fit. We anticipate that the mechanistic features of protein adsorption to an
      Au(111) surface revealed here can be extended to other inorganic surfaces and
      proteins and will therefore aid the design of specific protein-surface
      interactions. 

PMID- 27021900
TI  - Hormone therapy and large bowel cancer revisited.
AB  - Many studies have investigated potential links between postmenopausal hormone
      therapy (HT) and the risk for colorectal cancer. Most of these studies showed
      some reduction in risk, but association with the exact grade of the tumor or with
      cancer mortality is less consistent. Activation of estrogen receptor beta
      (ERbeta) related cellular pathways is probably the pathophysiological basis for
      this HT effect, since ERbetas exert antiproliferative and pro-apoptotic
      signaling, inhibit inflammatory signaling and modulate the tumor
      microenvironment. To note, the impact on health may not be substantial as the
      absolute numbers point at the order of only a few saved cases per 10 000 women
      per year of hormone use. 

PMID- 27021899
TI  - Digestive enzyme activity in the intestine of Nile tilapia (Oreochromis niloticus
      L.) under pond and cage farming systems.
AB  - The effect of different farming systems (cage, pond) upon digestive enzyme
      activities of Nile tilapia was evaluated. Juvenile Nile tilapia (87.61 +/- 1.52
      g) were simultaneously cultured in pond and cage systems during 90 days. Cages
      used nutritional biphasic plan (35 and 32 % crude protein-CP feeds) and ponds
      used nutritional triphasic plan (35, 32 and 28 % CP feeds). Biometric
      measurements were monthly performed for adjustments in feeding regimes and
      removal of intestine tissues to evaluate the performance of enzyme activities.
      Total proteolytic, amylase and lipase activities were not statistically different
      between the treatments throughout the periods analyzed (31, 63 and 94 days of
      culture). However, trypsin and chymotrypsin activities were higher with 31 and 63
      days of culture in fish from pond system, suggesting that natural food may have
      influenced these activities. A positive correlation was observed between the
      recommended concentration of essential amino acids for Nile tilapia and specific
      aminopeptidases activity in fish cage system. Substrate-SDS-PAGE revealed 12
      active proteolytic bands in both systems. However, integrated density (ID) values
      were higher in the bands of ponds. Specimens of either cage or pond exhibited
      five bands of amylolytic activity. Fish from cage and pond systems showed the
      highest values of ID within 31 days of cultivation. In this study, the complexity
      of digestive functions could be verified for animals maintained under commercial
      conditions. Some of the assessed enzymes may show adaptations of their activities
      and/or expression that allow the fish to achieve a more efficient nutrient
      assimilation. 

PMID- 27021901
TI  - [Harlequin phenomenon associated with neurological abnormalities: A case report].
AB  - BACKGROUND: Harlequin phenomenon consists of facial flush and erythrosis with
      unilateral sweating and pallor, associated with contralateral anhidrosis. We
      present the case of a child in whom the syndrome was associated with Horner's
      syndrome, epilepsy, mental and psychomotor retardation. PATIENTS AND METHODS: A 9
      year-old boy presented with right unilateral hemifacial erythema on effort, with
      normal colouring and Horner's syndrome on the left side of the face. His medical
      history revealed generalized myoclonic epilepsy, psychomotor delay and mental
      retardation. No underlying anomalies were identified. Harlequin phenomenon was
      diagnosed. DISCUSSION: Despite its stereotypical clinical features, Harlequin
      phenomenon is a poorly known disease. However, clinicians must be aware of it in
      order to determine the diagnosis and investigate for causes and any associated
      abnormalities. The underlying mechanism is an autonomic neuropathy affecting the
      sympathetic vasodilator neurons. To our knowledge, there have been no previous
      reports of Harlequin phenomenon in association with Horner syndrome, psychomotor
      delay and mental retardation.

PMID- 27021902
TI  - [Eruptive keratoacanthomas and leflunomide].

PMID- 27021903
TI  - Antitumor effects of cecropin B-LHRH' on drug-resistant ovarian and endometrial
      cancer cells.
AB  - BACKGROUND: Luteinizing hormone-releasing hormone receptor (LHRHr) represents a
      promising therapeutic target for treating sex hormone-dependent tumors. We
      coupled cecropin B, an antimicrobial peptide, to LHRH', a form of LHRH modified
      at carboxyl-terminal residues 4-10, which binds to LHRHr without interfering with
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. This
      study aimed to assess the antitumor effects of cecropin B-LHRH' (CB-LHRH') in
      drug-resistant ovarian and endometrial cancers. METHODS: To evaluate the
      antitumor effects of CB-LHRH', three drug resistant ovarian cancer cell lines
      (SKOV-3, ES-2, NIH:OVCAR-3) and an endometrial cancer cell line (HEC-1A) were
      treated with CB-LHRH'. Cell morphology changes were assessed using inverted and
      electron microscopes. In addition, cell growth and cell cytotoxicity were
      measured by MTT assay and LDH release, respectively. In addition, hemolysis was
      measured. Furthermore, radioligand receptor binding, hypersensitization and
      minimal inhibitory concentrations (against Staphylococcus aureus, Klebsiella
      pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, and
      Acinetobacter baumannii) were determined. Finally, the impact on tumor growth in
      BALB/c-nu mice was assessed in an ES-2 xenograft model. RESULTS: CB-LHRH' bound
      LHRHr with high-affinity (dissociation constant, Kd = 0.252 +/- 0.061 nM).
      Interestingly, CB-LHRH' significantly inhibited the cell viability of SKOV-3, ES
      2, NIH:OVCAR-3 and HEC-1A, but not that of normal eukaryotic cells. CB-LHRH' was
      active against bacteria at micromolar concentrations, and caused no
      hypersensitivity in guinea pigs. Furthermore, CB-LHRH' inhibited tumor growth
      with a 23.8 and 20.4 % reduction in tumor weight at 50 and 25 mg/kg.d,
      respectively. CONCLUSIONS: CB-LHRH' is a candidate for targeted chemotherapy
      against ovarian and endometrial cancers.

PMID- 27021904
TI  - Performance of Bipolar Disorder Patients in Attention Testing: Comparison with
      Normal Controls and Among Manic, Depressive, and Euthymic Phases.
AB  - Several studies on cognition in bipolar disorder (BD) have been developed on the
      last decade. Neuropsychological evaluation of attention in BD patients is
      fundamental since alterations in attention affect other cognitive functions.
      Evaluate if performance of BD patients in attention tests varies according to
      each phase of the disease and verify if there are differences in attention when
      comparing BD patients with normal controls. The study included 101 BD patients,
      with ages between 18 and 65 years, being 52 euthymic, 22 manic and 27 depressive,
      besides 30 normal controls. All subjects were evaluated though Hamilton
      Depression Scale, Young Mania Rating Scale and Global Assessment of Functioning,
      bipolar version (CGI-BP). Attention was evaluated through a neuropsychological
      battery. Normal controls had a better performance in selective attention tests
      than BD patients. No differences were found among manic, depressive and euthymic
      phases. Attention is markedly impaired in BD. Nevertheless, the results of this
      study do not imply that the severity of the attention deficit in BD patients
      varies according to decease phase.

PMID- 27021907
TI  - Impaired spleen structure and chemokine expression in ME7 scrapie-infected mice.
AB  - We have previously demonstrated that prion protein-deficient (Prnp(0/0)) Zurich I
      mice display impaired T zone structure resulting from decreased splenic
      expression of the T cell homing chemokines, CCL19 and CCL21. Prions are
      transported to, and colonise in, the secondary lymphoid tissues. Therefore, in
      order to investigate how scrapie infection affects the splenic white pulp
      structure, we infected C57BL/6 mice with the mouse-adapted scrapie strain ME7 and
      analysed end-stage prion disease. We found that the white pulp regions of ME7
      infected spleens were smaller, and contained markedly diminished T zones, as
      compared to control spleens. Although lymphoid tissue inducer cells were not
      affected, the expression of both CCL19 and CCL21 was decreased. In addition, the
      networks of follicular dendritic cells, which are known to express high levels of
      the cellular prion protein (PrP(C)) and to accumulate PrP(Sc) following scrapie
      infection, were larger in ME7-infected spleens. Further, they were associated
      with increased numbers of B cells expressing high levels of IgM. These data
      indicate that ME7-infected spleens display phenotype characteristics different
      from those reported for Prnp(0/0) spleens mainly due to the gain of PrP(Sc)
      function and suggest that the PrP(C) is required, not only to form the splenic
      white pulp structure, but also to maintain the intact T zone structure.

PMID- 27021905
TI  - Neurofilament depletion improves microtubule dynamics via modulation of
      Stat3/stathmin signaling.
AB  - In neurons, microtubules form a dense array within axons, and the stability and
      function of this microtubule network is modulated by neurofilaments. Accumulation
      of neurofilaments has been observed in several forms of neurodegenerative
      diseases, but the mechanisms how elevated neurofilament levels destabilize axons
      are unknown so far. Here, we show that increased neurofilament expression in
      motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed
      microtubule dynamics. The disease is caused by a point mutation in the tubulin
      specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal
      amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes
      instable which then results in destabilization of axonal microtubules and defects
      in axonal transport, in particular in motoneurons. Depletion of neurofilament
      increases the number and regrowth of microtubules in pmn mutant motoneurons and
      restores axon elongation. This effect is mediated by interaction of neurofilament
      with the stathmin complex. Accumulating neurofilaments associate with stathmin in
      axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout
      increases Stat3-stathmin interaction and stabilizes the microtubules in pmn
      mutant motoneurons. Consequently, counteracting enhanced neurofilament expression
      improves axonal maintenance and prolongs survival of pmn mutant mice. We propose
      that this mechanism could also be relevant for other neurodegenerative diseases
      in which neurofilament accumulation and loss of microtubules are prominent
      features.

PMID- 27021908
TI  - First case in Spain of septic shock by Streptococcus suis possible food-borne.

PMID- 27021906
TI  - CSF biomarkers associated with disease heterogeneity in early Parkinson's
      disease: the Parkinson's Progression Markers Initiative study.
AB  - The development of biomarkers to predict the progression of Parkinson's disease
      (PD) from its earliest stage through its heterogeneous course is critical for
      research and therapeutic development. The Parkinson's Progression Markers
      Initiative (PPMI) study is an ongoing international multicenter, prospective
      study to validate biomarkers in drug-naive PD patients and matched healthy
      controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (alpha
      syn), amyloid-beta1-42 (Abeta1-42), total tau (t-tau), and tau phosphorylated at
      Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with
      measures of the clinical features of these subjects. We found that CSF alpha-syn,
      t-tau and p-tau levels, but not Abeta1-42, were significantly lower in PD
      compared with HC, while the diagnostic value of the individual CSF biomarkers for
      PD diagnosis was limited due to large overlap. The level of alpha-syn, but not
      other biomarkers, was significantly lower in PD patients with non-tremor-dominant
      phenotype compared with tremor-dominant phenotype. In addition, in PD patients
      the lowest Abeta1-42, or highest t-tau/Abeta1-42 and t-tau/alpha-syn quintile in
      PD patients were associated with more severe non-motor dysfunction compared with
      the highest or lowest quintiles, respectively. In a multivariate regression
      model, lower alpha-syn was significantly associated with worse cognitive test
      performance. APOE epsilon4 genotype was associated with lower levels of Abeta1
      42, but neither with PD diagnosis nor cognition. Our data suggest that the
      measurement of CSF biomarkers in early-stage PD patients may relate to disease
      heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed
      to define their prognostic performance.

PMID- 27021909
TI  - Epithelial, non-melanocytic and melanocytic proliferations of the ocular surface.
AB  - Ocular surface tumors are commonly encountered by ophthalmologists and ophthalmic
      pathologists. These tumors have varied clinical manifestations. In this article,
      we discuss the most commonly encountered non-melanocytic and melanocytic ocular
      surface tumors, with emphasis on their common clinical features, morphologic
      patterns, and prognostic factors. 

PMID- 27021910
TI  - Current Status of Robot-Assisted Radical Cystectomy and Intracorporeal Urinary
      Diversion.
AB  - Robot-assisted surgery has become a widely used surgical approach in the
      management of urologic malignancies. With its initial experience in the treatment
      of prostate cancer, the technology rapidly expanded to other urologic
      malignancies including bladder cancer. Since its introduction in 2003, robot
      assisted radical cystectomy has seen refinement and increased penetration over
      the last decade. Furthermore, urologic surgeons have expanded its use to perform
      urinary diversions. The concept of intracorporeal urinary diversion is still in
      development but continues to see increased refinement among high volume academic
      centers. 

PMID- 27021911
TI  - Current Status of Minimally Invasive Surgery for Renal Cell Carcinoma.
AB  - Over the last three decades, the incidence of renal cell carcinoma (RCC) has
      continuously risen, generally attributed to the increased use of cross-sectional
      imaging across all medical disciplines. Fortunately, despite this rising
      incidence, the estimated 5-year relative survival rate has improved. This
      survival improvement likely parallels the stage migration of the last two decades
      toward an increased incidence of small renal masses (SRMs). However, this
      survival improvement may be secondary to improved surgical techniques and medical
      therapies for these malignancies. The increased incidence of SRMs has led to an
      expected evolution in the treatment of RCC. Minimally invasive surgical
      applications for the treatment of RCC have gained widespread popularity, and now
      these approaches to renal malignancies have surpassed open techniques in
      frequency of utilization. Laparoscopic and robotic-assisted techniques have now
      been applied to both radical and partial nephrectomy procedures of varying
      complexity. Additionally, percutaneous ablative procedures have been applied to
      the treatment of some SRMs, increasing the urologist's armamentarium further.
      Below, we provide a review of these minimally invasive surgical (MIS) procedures
      for the treatment of RCC. 

PMID- 27021912
TI  - Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular
      injury in Labrador retrievers.
AB  - Common parenchymal liver diseases in dogs include reactive hepatopathies and
      primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a
      long subclinical phase. Specific clinical signs become overt only when liver
      damage is severe and in this phase, treatment is usually less effective. Limited
      data are available regarding the sensitivity of liver enzyme activity or
      biomarkers for early detection of subclinical hepatitis. Hepatocyte-derived
      microRNAs (HDmiRs) were recently identified as promising biomarkers for
      hepatocellular injury in multiple species. Here, the potential of the HDmiRs miR
      122 and miR-148a as sensitive diagnostic biomarkers for hepatocellular injury in
      Labrador retrievers was investigated. Samples from 66 Labrador retrievers with
      histologically normal livers, high hepatic copper, and with various forms of
      liver injury were evaluated for serum alanine aminotransferase (ALT) activity and
      microRNA values. Median values of HDmiR-122 were 34.6 times higher in dogs with
      liver injury and high ALT than in normal dogs (95% confidence intervals [CI], 13
      95; P <0.001). HDmiR-122 values were significantly increased in dogs with liver
      injury and normal ALT (4.2 times; 95% CI, 2-12; P <0.01) and in dogs with high
      hepatic copper concentrations and unremarkable histopathology (2.9 times; 95% CI,
      1.1-8.0; P <0.05). Logistic regression analyses demonstrated that miR-122 and miR
      148a were both predictors of hepatocellular injury. The sensitivity of miR-122
      was 84% (95% CI, 73-93%), making it superior to ALT (55%; 95% CI, 41-68%) for the
      detection of hepatocellular injury in Labrador retrievers (P <0.001). This study
      demonstrated that serum HDmiR, particularly miR-122, is a highly sensitive marker
      for the detection of hepatocellular injury in Labrador retrievers and is a
      promising new biomarker that may be used for early detection of subclinical
      hepatitis in dogs. 

PMID- 27021913
TI  - Enhancing the enantioselective recognition and sensing of chiral anions by
      halogen bonding.
AB  - Chiral halogen bonding (S)-BINOL-based receptors are demonstrated to enhance the
      enantioselective recognition and sensing of chiral anions compared to their
      hydrogen bonding analogues. Computational studies attribute this behaviour to the
      strict linearity of halogen bonding (XB) and steric environment conferred by the
      XB donor groups bridged by the (S)-BINOL motif. 

PMID- 27021915
TI  - Comparative analysis of microRNA profiles of rice anthers between cool-sensitive
      and cool-tolerant cultivars under cool-temperature stress.
AB  - Plants subjected to abiotic stress can regulate gene expression post
      transcriptionally by means of small RNAs such as microRNAs. Cool-temperature
      stress causes abnormal tapetum hypertrophy in rice anthers, leading to pollen
      sterility. As a first step toward understanding the molecular mechanisms of cool
      tolerance in developing anthers of rice, we report here a comprehensive
      comparative analysis of microRNAs between cool-sensitive Sasanishiki and cool
      tolerant Hitomebore cultivars. High-throughput Illumina sequencing revealed 241
      known and 46 novel microRNAs. Interestingly, 15 of these microRNAs accumulated
      differentially in the two cultivars at the uninucleate microspore stage under
      cool conditions. Inverse correlations between expression patterns of microRNAs
      and their target genes were confirmed by quantitative RT-PCR analysis, and
      cleavage sites of some of the target genes were determined by 5' RNA ligase
      mediated RACE experiments. Thus, our data are useful resources to elucidate
      microRNA-mediated mechanism(s) of cool tolerance in rice anthers at the booting
      stage.

PMID- 27021914
TI  - Significance of alpha smooth muscle actin expression in traumatic painful
      neuromas: a pilot study in rats.
AB  - Treatment of painful neuromas remains a challenge and the mechanism of neuroma
      associated pain is not yet fully understood. In this study, we aimed to observe
      the expression of alpha smooth muscle actin (alpha-SMA) in traumatic neuromas and
      to investigate its possible roles in the cause of neuropathic pain in a rat
      model. The rat sciatic nerve was used and the experiment was divided into two
      parts. In part I, our results showed significantly higher levels of alpha-SMA and
      the pain marker c-fos in the autotomy group than in the no-autotomy group. In
      part II, the expression of alpha-SMA in neuromas was down- and up-regulated using
      SB-431542 and GW9662, respectively. A significant correlation between autotomy
      scores and the expression level of alpha-SMA was found (R = 0.957; p < 0.001) and
      the expression level of alpha-SMA was positively related to the autotomy scores
      (R(2) = 0.915, p < 0.001). We concluded that the expression of alpha-SMA plays
      certain roles in the neuroma-associated pain, either as a direct cause of pain or
      as an indirect marker of existence of local mechanical stimuli. Our findings may
      provide new insights into the development of new treatment modalities for the
      management of intractable painful neuromas.

PMID- 27021916
TI  - Evolution of GC content in the histone gene repeating units from Drosophila
      lutescens, D. takahashii and D. pseudoobscura.
AB  - A subset of histone genes (H1, H2A, H2B and H4), which are encoded along with H3
      within repeating units, were analyzed in Drosophila lutescens, D. takahashii and
      D. pseudoobscura to investigate the evolutionary mechanisms influencing this
      multigene family and its GC content. Nucleotide divergence among species was more
      marked in the less functional regions. A strong inverse relationship was observed
      between the extent of evolutionary divergence and GC content within the repeating
      units; this finding indicated that the functional constraint on a region must be
      associated with both divergence and GC content. The GC content at 3(rd) codon
      positions in the histone genes from D. lutescens and D. takahashii was higher
      than that from D. melanogaster, while that from D. pseudoobscura was similar.
      These evolutionary patterns were similar to those of H3 gene regions. Based on
      these findings, we propose that the evolutionary mechanisms governing nucleotide
      content at 3(rd) codon positions tend to eliminate A and T nucleotides more
      frequently than G and C nucleotides. These changes might be the consequence of
      negative selection and would result in GC-rich 3(rd) codon positions. In
      addition, interspecific differences in GC content, which exhibited the same
      pattern for all histone genes, could be explained by different selection
      efficiencies that result from changes in population size. 

PMID- 27021917
TI  - Factors underlying natural variation in body pigmentation of Drosophila
      melanogaster.
AB  - Molecular mechanisms underlying standing genetic variation of an ecologically
      relevant trait such as pigmentation trait variation in a model insect, Drosophila
      melanogaster, are relevant to our understanding of different kinds of
      intergenomic interactions. In this study, we focused on the association between
      body pigmentation and stress resistance, and on genotype-by-environment
      interaction, both of which are likely to contribute to the persistence of
      phenotypic variation in a natural population. First, we detected a significant
      association between pigmentation traits in females and starvation resistance
      (darker strains were weaker) and a weak association between pigmentation and
      chill coma recovery time (darker strains showed shorter recovery time) among 20
      inbred strains from the Drosophila melanogaster Genetic Reference Panel (DGRP),
      which originated from a natural population in North America. These associations
      revealed a complex relationship between body pigmentation and physiological
      traits that may give rise to balanced selective forces acting on the traits under
      fluctuating environmental conditions. Second, using four of the DGRP strains, a
      substantial degree of genotype (strain) * environment (rearing temperature)
      interaction was detected among expression levels of the genes encoding effector
      enzymes in the melanin biosynthesis pathway. These interactions can potentially
      reduce the efficiency of purifying selection on the pigmentation traits over a
      wide range of temperature conditions. Finally, we discuss possible mechanisms
      that contribute to the maintenance of the standing pigmentation variation in this
      species.

PMID- 27021919
TI  - Travelling wave analysis of a mathematical model of glioblastoma growth.
AB  - In this paper we analyse a previously proposed cell-based model of glioblastoma
      (brain tumour) growth, which is based on the assumption that the cancer cells
      switch phenotypes between a proliferative and motile state (Gerlee and Nelander,
      2012). The dynamics of this model can be described by a system of partial
      differential equations, which exhibits travelling wave solutions whose wave speed
      depends crucially on the rates of phenotypic switching. We show that under
      certain conditions on the model parameters, a closed form expression of the wave
      speed can be obtained, and using singular perturbation methods we also derive an
      approximate expression of the wave front shape. These new analytical results
      agree with simulations of the cell-based model, and importantly show that the
      inverse relationship between wave front steepness and speed observed for the
      Fisher equation no longer holds when phenotypic switching is considered.

PMID- 27021918
TI  - Applicability of the Rayleigh equation for enantioselective metabolism of chiral
      xenobiotics by microsomes, hepatocytes and in-vivo retention in rabbit tissues.
AB  - In this study we propose a new approach for analyzing the enantioselective
      biodegradation of some antidepressant drugs mediated by human and rat liver
      microsomes by using the Rayleigh equation to describe the enantiomeric enrichment
      conversion dependencies. Analysis of reported degradation data of additional six
      pesticides, an alpha blocker and a flame retardant by microsomes or hepatocytes
      in vitro reaffirmed the universality of the approach. In all the in vitro studied
      cases that involved enantioselective degradation, a Rayleigh dependence of the
      enantiomeric enrichment was observed. Published data regarding in vivo retention
      of myclobutanil in liver, kidney, muscle and brain tissues of rabbits following
      injection of the racemate were remodeled showing prevalence of the Rayleigh law
      for the chiral enrichment of the fungicide in the various tissues. This approach
      will revolutionize data organization in metabolic pathway research of target
      xenobiotics by either liver microsomes, hepatocytes or their organ-specific in
      vivo retention. The fact that the enantiomeric enrichment as a function of the
      conversion can be described by a single quantifier, will pave the road for the
      use of structure activity predictors of the enantiomeric enrichment and for
      mechanistic discrimination based on parametric dependence of the quantifier. 

PMID- 27021920
TI  - Porosity of silica Stober particles determined by spin-echo small angle neutron
      scattering.
AB  - Stober silica particles are used in a diverse range of applications. Despite
      their widespread industrial and scientific uses, information on the internal
      structure of the particles is non-trivial to obtain and is not often reported. In
      this work we have used spin-echo small angle neutron scattering (SESANS) in
      conjunction with ultra small angle X-ray scattering (USAXS) and pycnometry to
      study an aqueous dispersion of Stober particles. Our results are in agreement
      with models which propose that Stober particles have a porous core, with a
      significant fraction of the pores inaccessible to solvent. For samples prepared
      from the same master sample in a range of H2O : D2O ratio solutions we were able
      to model the SESANS results for the solution series assuming monodisperse, smooth
      surfaced spheres of radius 83 nm with an internal open pore volume fraction of
      32% and a closed pore fraction of 10%. Our results are consistent with USAXS
      measurements. The protocol developed and discussed here shows that the SESANS
      technique is a powerful way to investigate particles much larger than those
      studied using conventional small angle scattering methods. 

PMID- 27021921
TI  - Pushing the frontiers of operative treatment of hydatid liver disease a step
      forward.

PMID- 27021922
TI  - In vitro and in vivo effects of the phytohormone inhibitor fluridone against
      Neospora caninum infection.
AB  - Neospora caninum causes abortion and stillbirth in cattle. Identification of
      effective drugs against this parasite remains a challenge. Previous studies have
      suggested that disruption of abscisic acid (ABA)-mediated signaling in
      apicomplexan parasites such as Toxoplasma gondii offers a new drug target. In
      this study, the ABA inhibitor, fluridone (FLU), was evaluated for its action
      against N. caninum. Production of endogenous ABA within N. caninum was confirmed
      by ultra-performance liquid chromatography-tandem quadruple mass spectrometry.
      Subsequently, FLU treatment efficacy was assessed using in vitro. Results
      revealed that FLU inhibited the growth of N. caninum and T. gondii in vitro (IC50
      143.1+/-43.96MUM and 330.6+/-52.38MUM, respectively). However, FLU did not affect
      parasite replication at 24h post-infection, but inhibited egress of N. caninum
      thereafter. To evaluate the effect of FLU in vivo, N. caninum-infected mice were
      treated with FLU for 15days. FLU treatment appeared to ameliorate acute
      neosporosis induced by lethal parasite challenge. Together, our data shows that
      ABA might control egress in N. caninum. Therefore, FLU has potential as a
      candidate drug for the treatment of acute neosporosis. 

PMID- 27021923
TI  - What is a Caucasian 'fine' hair? Comparing instrumental measurements, self
      perceptions and assessments from hair experts.
AB  - OBJECTIVE: To determine the various factors contributing to what Caucasian women
      describe as 'fine hair'. METHODS: Three complementary approaches were used,
      namely self-evaluation by the volunteer, assessment by a sensorial expert and
      instrumental measurements, in order to determine some of the possible parameters
      taken into account by Caucasian women when they describe the notion of fine hair.
      One hundred fifty one women of Caucasian origin participated in the study. They
      varied in age, and varied in that some considered themselves as having fine hair,
      and others not. The instrumental measurements carried out included hair diameter
      measurements, hair density measurements, hair breakage force, hair flexibility
      and scalp sebum levels. RESULTS: From six parameters defined initially, four
      parameters were found to be in common with the three approaches: hair abundance
      (density), hair thickness, hair resistance and the volume of the hair on the
      head. The commonly used term 'body' was only common to self and expert
      evaluation, whereas the influence of curliness was only common to expert
      evaluation and instrumental measurements. CONCLUSIONS: This study has shown close
      agreement between sensorial and instrumental findings, and also illustrates how
      the women participating can subtly and adequately describe their own hair. It is
      important to note that the words 'fine hair' describes a lot more than just
      physically thin hair fibres. Ageing is an additional factor that clearly impacts
      certain parameters associated with 'fine hair' among the volunteers.

PMID- 27021924
TI  - The dynamics of interacting folds under biaxial compressive stresses.
AB  - The gradual in-plane compression of a solid film bonded to a soft substrate can
      lead to surface wrinkling and even to the formation of a network of folds for
      sufficiently high strain. An understanding of how these folds initiate,
      propagate, and interact with each other is still lacking. In a previous study, we
      developed an experimental system to observe the wrinkle-to-fold transition of
      layered elastic materials under biaxial compressive stresses. Here we focus on
      the dynamic interaction of a pair of propagating folds under biaxial compression.
      We find experimentally that their behavior is mediated through their tips and
      depends on the separation of the tips and their angle of interception. When the
      angle is lower than 45 degrees , the two folds either form a unique fold by the
      coalescence of their tips when close enough, or bend their trajectories to
      intersect each other and form a lenticular region in analogy with cracks. When
      the angle is higher then 45 degrees , the folds simply intersect and form a T
      like junction. We rationalize this behavior by conducting numerical simulations
      to visualize the stress field around the two tips and find that the initial
      geometric position of the tips primarily determines the final state of the folds.

PMID- 27021925
TI  - RX of sickle cell leg ulcers.

PMID- 27021926
TI  - [Fertility preservation in women of the childbearing age: Indications and
      strategies].
AB  - Advances on cryopreservation techniques now allow considering oocyte, embryo or
      ovarian tissue freezing for female fertility preservation. Originally developed
      for patients suffering from cancer, fertility preservation has rapidly invaded
      others medical fields, and represents now the standard of care for all young
      patient diagnosed with a disease that could impair fertility or having to receive
      possibly gonadotoxic treatment. As a result, autoimmune diseases, some genetic
      pathologies or iterative pelvic surgeries, at risk of premature ovarian failure,
      have become common indications of fertility preservation. In addition, the social
      egg freezing aiming at preventing the age-related fertility decline is still
      debated in France, although authorized in numerous countries. This review will
      discuss the different strategies of fertility preservation in young girls and
      women of reproductive age, regarding different medical or non-medical
      indications. 

PMID- 27021927
TI  - [Uterine rupture plugged by omentum in a rudimentary horn pregnancy: About a rare
      case].
AB  - Pregnancy in a rudimentary horn of a pseudo-horned uterus is a rare obstetrical
      situation, for which, maternal-fetal prognosis is altered by the risk of uterine
      rupture. We report a rare case of pregnancy in a rudimentary horn with birth of a
      living child at 28 weeks of amenorrhea. During caesarean, uterine rupture plugged
      by the omentum was observed. We discuss from this case obstetric management of
      this pathology. 

PMID- 27021928
TI  - Cetuximab treatment alters the content of extracellular vesicles released from
      tumor cells.
AB  - AIM: Extracellular vesicles (EVs) are attractive candidates for biomarker
      research, because their content reflects the parental cell status. This study
      aimed to examine whether tumor cell derived EVs mirrored the cellular changes
      caused by treatment with cetuximab, a therapeutic antibody that blocks activation
      of EGF receptor (EGFR). MATERIALS & METHODS: A-431 cells were treated with
      cetuximab for 48 h. EVs were isolated using differential centrifugation and
      protein content was analyzed using western blotting. RESULTS: EV levels of EGFR
      and phospho-EGFR were reduced after cetuximab treatment, reflecting similar
      changes in the parental cells. In addition, cetuximab was found associated with
      EVs. CONCLUSION: EVs could serve as biomarkers to monitor cetuximab treatment.
      Association of cetuximab with EVs might influence its behavior.

PMID- 27021929
TI  - Renal cell carcinoma in end-stage renal disease: Multi-institutional comparative
      analysis of survival.
AB  - OBJECTIVES: To describe the clinical features of renal cell carcinoma arising in
      end-stage renal disease and to compare survival outcomes after definitive
      treatment with non-end-stage renal disease renal cell carcinoma. METHODS: Data of
      181 consecutive patients with end-stage renal disease renal cell carcinoma who
      had received surgical treatment between 1995 and 2011 at seven institutions were
      reviewed. Data of 362 non-end-stage renal disease renal cell carcinoma patients
      matched for clinicopathological parameters who received surgery at Asan Medical
      Center during the same study period were also reviewed. The two study groups were
      compared with respect to recurrence-free, cancer-specific, and overall survival
      by Kaplan-Meier analysis and Cox proportional hazards method. Mean follow up was
      40 +/- 34.2 months after surgery. RESULTS: Median tumor size was 2.5 cm
      (interquartile range 1.5-4.5), and pathological tumor stage was T1 in 78%, T2 in
      7.1% and T3 and higher in 14.9%. Tumor histological type was clear cell in 63%,
      papillary in 17%, chromophobe in 5%, clear cell papillary in 2.8% and acquired
      cystic disease-related in 6.1%. Compared with the controls, the stage-specific 5
      year recurrence-free survival was similar (87.6 vs 88.5%), but cancer-specific
      and overall survival was significantly lower. On multivariate analysis, end-stage
      renal disease renal cell carcinoma was not a predictor for recurrence-free
      survival, but a significant predictor for cancer-specific (hazard ratio 4.07, 95%
      confidence interval 2.08-7.94) and overall survival (hazard ratio 3.13, 95%
      confidence interval 1.66-5.96). CONCLUSIONS: End-stage renal disease renal cell
      carcinoma seems to have comparable stage-specific recurrence-free, but poorer
      cancer-specific and overall survival compared with non-end-stage renal disease
      renal cell carcinoma. As patients with end-stage renal disease are a high-risk
      population for renal cell carcinoma, routine radiographic screening to improve
      survival outcomes should be further investigated.

PMID- 27021930
TI  - Design and development of histone deacetylase (HDAC) chemical probes for cell
      based profiling.
AB  - Histone deacetylases (HDACs) contribute to regulation of gene expression by
      mediating higher-order chromatin structures. They assemble into large
      multiprotein complexes that regulate activity and specificity. We report the
      development of small molecule probes with class IIa and pan-HDAC activity that
      contain photoreactive crosslinking groups and either a biotin reporter, or a
      terminal alkyne handle for subsequent bioorthogonal ligation. The probes retained
      inhibitory activity against recombinant HDAC proteins and caused an accumulation
      of acetylated histone and tubulin following cell treatment. The versatility of
      the probes has been demonstrated by their ability to photoaffinity modify HDAC
      targets in vitro. An affinity enrichment probe was used in conjunction with mass
      spectrometry proteomics to isolate HDACs and their interacting proteins in a
      native proteome. The performance of the probes in recombinant versus cell-based
      systems highlights issues for the development of chemoproteomic technologies
      targeting class IIa HDACs in particular.

PMID- 27021931
TI  - The Cambridge Breast Intensity-modulated Radiotherapy Trial: Comparison of
      Clinician- versus Patient-reported Outcomes.
AB  - AIMS: Breast radiotherapy-associated toxicity is often reported using clinical
      and photographic assessments. The addition of patient-reported outcome measures
      (PROMs) is becoming more common. This study investigated the concordance between
      clinician- and patient-reported outcomes. MATERIALS AND METHODS: The Cambridge
      Breast Intensity-modulated Radiotherapy (IMRT) trial prospectively collected data
      on clinician assessment and PROMs at 2 and 5 years after breast radiotherapy.
      Clinician assessment included physical examination and photographic assessment.
      PROMs included European Organization for Research and Treatment of Cancer (EORTC)
      BR23 questionnaire and four breast radiotherapy-specific questions. The
      correlation between patient and clinician scores were analysed on an independent
      patient basis using percentage agreement, Cohen's kappa coefficient (k) and
      Bowker's test of symmetry. The analysis was repeated after stratifying patients
      based on age, baseline Hospital Anxiety and Depression Score (HADS) and baseline
      body image score. RESULTS: At 2 and 5 years, a weak level of concordance was seen
      between the clinician-based assessment and PROMS for all the five toxicity end
      points (k = 0.05-0.21), with individual patient-based agreement of 32.9-78.3% and
      a highly discordant Bowker's test of symmetry (P < 0.001). The most frequently
      reported moderate-severe toxicity by patients was change in breast appearance
      (14% at both 2 and 5 years), whereas it was breast induration (36% and 25% at 2
      and 5 years, respectively) by the clinicians. The lack of concordance was not
      affected by patient's age, baseline HADS and baseline body image score.
      CONCLUSIONS: This study found that moderate-severe toxicity reported by patients
      is low and the overall concordance between clinicians and patients is low. This
      could be due to methodological limitations or alternatively reflects the
      subjective nature of PROMs. Incorporation of a patient's perception on treatment
      related toxicity will have important implications for treatment decisions and
      follow-up care.

PMID- 27021932
TI  - Human resources needed to perform antimicrobial stewardship teams' activities in
      French hospitals.
AB  - OBJECTIVE: In January 2015, the French ministry of Health set up a task force on
      antibiotic resistance. Members of the task force's "antimicrobial stewardship"
      group conducted a study to evaluate the human resources needed to implement all
      the required activities of the multidisciplinary antimicrobial stewardship teams
      (AST - antibiotic/infectious disease lead supervisors, microbiologists, and
      pharmacists) in French healthcare facilities. METHODS: We conducted an online
      cross-sectional nationwide survey. The questionnaire was designed based on
      regulatory texts and experts' consensus. The survey took place between March and
      May 2015. We used the mailing list of the French Infectious Diseases Society
      (SPILF) to send out questionnaires. RESULTS: A total of 65 healthcare facilities
      completed the questionnaire. The human resources needed to implement all AST's
      activities were estimated at 3.6 full-time equivalent (FTE) positions/1000 acute
      care beds for antibiotic/infectious disease lead supervisors, at 2.5 FTE/1000
      beds for pharmacists, and at 0.6 FTE/1000 beds for microbiologists. This almost
      amounts to a total of 2000 FTE positions for all healthcare facilities (public
      and private) in France and to an annual cost of 200 million euros. CONCLUSION:
      Dedicated and sustainable funding for AST is urgently needed to implement
      comprehensive and functional AST programs in all healthcare facilities.

PMID- 27021933
TI  - Diagnosis of latent tuberculosis by ELISPOT assay and tuberculin skin test.
AB  - OBJECTIVE: To determine the prevalence of latent tuberculosis infection (LTBI) in
      college students. PATIENTS AND METHODS: Four hundred and twenty newly admitted
      college students were enrolled. The Enzyme-Linked ImmunoSpot assay (ELISPOT) was
      used. Overall, 171 students with ELISPOT assay+/TST+ were monitored for three
      years to detect active TB disease. RESULTS: The overall positive rate of ELISPOT
      assay was 40.7% among TST+ students. The ELISPOT positive rates were 36.9%,
      45.4%, and 64.3% in groups of TST induration of 10-14mm, 15-20mm, and >=20mm,
      respectively, with a significant difference (chi(2)=10.136, P<0.01) but no
      significant difference between BCG scar and no scar (41.2% vs. 38.8%; P>0.05).
      None of the 171 untreated students contracted active TB within the three-year
      monitoring period. CONCLUSION: The LTBI rate might be overestimated by TST
      compared with interferon-gamma release assays. On the basis of a close
      monitoring, few students developed active TB despite a positive result to the TST
      and ELISPOT assay.

PMID- 27021934
TI  - Left Ventricular Global Strain for Estimating Relaxation and Filling Pressure - A
      Multicenter Study.
AB  - BACKGROUND: Speckle-tracking echocardiography (STE)-derived parameters may have
      better correlation with left ventricular (LV) relaxation and filling pressure
      than tissue Doppler-derived parameters. However, it has not been elucidated which
      parameter - strain or strain rate - and which direction of myocardial deformation
      - longitudinal or circumferential - is the most useful marker of LV relaxation
      and filling pressure. METHODS AND RESULTS: We conducted a prospective multicenter
      study and compared the correlation of tissue Doppler- and STE-derived parameters
      with the time constant of LV pressure decay (tau) and LV mean diastolic pressure
      (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity
      (e') with tau was weak (r=-0.32, P<0.01), and that of peak longitudinal strain
      (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There
      was a modest correlation between LVMDP and the ratio of early-diastolic inflow
      velocity (E) to e' (E/e') (r=0.50, P<0.001). In contrast, the ratio of E to LS
      (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS
      with LVMDP was significantly better than that for E/e' (P<0.01). Receiver
      operating characteristic analysis showed that E/LS had the largest area under the
      curve for distinguishing elevated LVMDP (E/LS 0.86, E/e' 0.74, E/A 0.67).
      CONCLUSIONS: STE-derived longitudinal parameters correlated well with LV
      relaxation and filling pressure. In particular, E/LS could be more accurate than
      E/e' for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).

PMID- 27021935
TI  - Zika Virus: A Basic Overview of an Emerging Arboviral Infection in the Western
      Hemisphere.
AB  - Since February 2015, Zika virus has spread throughout the Western Hemisphere,
      starting in Brazil. As of March 2016, autochthonous transmission has been
      reported in at least 31 countries or territories. For countries in the Americas,
      the spread of Zika virus, a previously unfamiliar disease, follows similar
      emerging infection introductions of West Nile virus and Chikungunya virus and
      their spread throughout the American continents and the Caribbean nations. The
      Pan American Health Organization and the World Health Organization have issued
      alerts and a Public Health Emergency of International Concern announcement
      related to the recent cluster of microcephaly cases and other neurological
      disorders in Brazil that are temporally associated with Zika virus, which
      highlights the possible adverse impact of viral infection. This article provides
      an overview of the Zika virus infection and presents the historical background of
      the virus, a description of the pathogen, the epidemiology and clinical spectrum
      of Zika virus infection, diagnosis and treatment approaches, and prevention and
      control measures. Understanding what is known about the virus and its clinical
      presentation will assist in prevention, detection, and response measures to
      reduce and control the spread of the virus throughout the Western Hemisphere.
      (Disaster Med Public Health Preparedness. 2016;page 1 of 6).

PMID- 27021936
TI  - This Month in AJP.
AB  - The following highlights summarize research articles that are published in the
      current issue of The American Journal of Pathology. 

PMID- 27021937
TI  - Mechanisms of Lung Fibrosis Resolution.
AB  - Fibrogenesis involves a dynamic interplay between factors that promote the
      biosynthesis and deposition of extracellular matrix along with pathways that
      degrade the extracellular matrix and eliminate the primary effector cells.
      Opposing the often held perception that fibrotic tissue is permanent, animal
      studies and clinical data now demonstrate the highly plastic nature of organ
      fibrosis that can, under certain circumstances, regress. This review describes
      the current understanding of the mechanisms whereby the lung is known to resolve
      fibrosis focusing on degradation of the extracellular matrix, removal of
      myofibroblasts, and the role of inflammatory cells. Although there are
      significant gaps in understanding lung fibrosis resolution, accelerated
      improvements in biotechnology and bioinformatics are expected to improve the
      understanding of these mechanisms and have high potential to lead to novel and
      effective restorative therapies in the treatment not only of pulmonary fibrosis,
      but also of a wide-ranging spectrum of chronic disorders.

PMID- 27021938
TI  - Thalamus plays a central role in ongoing cortical functioning.
AB  - Several challenges to current views of thalamocortical processing are offered
      here. Glutamatergic pathways in thalamus and cortex are divided into two distinct
      classes: driver and modulator. We suggest that driver inputs are the main
      conduits of information and that modulator inputs modify how driver inputs are
      processed. Different driver sources reveal two types of thalamic relays: first
      order relays receive subcortical driver input (for example, retinal input to the
      lateral geniculate nucleus), whereas higher order relays (for example, pulvinar)
      receive driver input from layer 5 of cortex and participate in cortico-thalamo
      cortical (or transthalamic) circuits. These transthalamic circuits represent an
      unappreciated aspect of cortical functioning, which I discuss here. Direct
      corticocortical connections are often paralleled by transthalamic ones.
      Furthermore, driver inputs to thalamus, both first and higher order, typically
      arrive via branching axons, and the transthalamic branch often innervates
      subcortical motor centers, leading to the suggestion that these inputs to
      thalamus serve as efference copies. 

PMID- 27021940
TI  - Rare genetic variants and schizophrenia.

PMID- 27021941
TI  - How (not) to silence long-range projections with light.

PMID- 27021942
TI  - And the beat goes on: from clock to behavior.

PMID- 27021939
TI  - Modeling ALS with motor neurons derived from human induced pluripotent stem
      cells.
AB  - Directing the differentiation of induced pluripotent stem cells into motor
      neurons has allowed investigators to develop new models of amyotrophic lateral
      sclerosis (ALS). However, techniques vary between laboratories and the cells do
      not appear to mature into fully functional adult motor neurons. Here we discuss
      common developmental principles of both lower and upper motor neuron development
      that have led to specific derivation techniques. We then suggest how these motor
      neurons may be matured further either through direct expression or administration
      of specific factors or coculture approaches with other tissues. Ultimately,
      through a greater understanding of motor neuron biology, it will be possible to
      establish more reliable models of ALS. These in turn will have a greater chance
      of validating new drugs that may be effective for the disease. 

PMID- 27021943
TI  - Fight club for mice.

PMID- 27021944
TI  - Erratum: Schizophrenia and brain volume genetic covariation.

PMID- 27021945
TI  - Erratum: Causal contribution of primate auditory cortex to auditory perceptual
      decision-making.

PMID- 27021946
TI  - Corrigendum: Stimulus-specific combinatorial functionality of neuronal c-fos
      enhancers.

PMID- 27021947
TI  - Endoscopically Determined Stone Clearance Predicts Disease Recurrence Within 5
      Years After Retrograde Intrarenal Surgery.
AB  - OBJECTIVE: To assess stone-related events (SREs) requiring retreatment in a
      series of 100 consecutive patients treated by retrograde intrarenal surgery
      (RIRS) for renal stones and to evaluate potential risk factors thereof. PATIENTS
      AND METHODS: The primary outcome was incidence of SRE (medical or surgical
      treatment). Secondary outcomes included side of SRE, time to SRE, and late
      complications. Analysis of potential risk factors included high-risk stone
      formers (HRSFs), obesity, high stone burden, and lower pole stones. In addition,
      we evaluated endoscopically determined small residual fragments (SRF) of <1 mm
      (i.e., fragments too small for retrieval) as an independent risk factor. RESULTS:
      Eighty-five of the 99 patients were followed up for a mean of 59 months (31-69),
      among whom 26 (30.1%) had SRE. Thirty-four of the 85 (40%) patients were HRSFs,
      22 of whom experienced SRE (both sides) during follow-up (64.7%, p < 0.001).
      Eight of the 17 patients (47.1%) with SRF experienced ipsilateral side SRE
      compared with 13 (19.1%) of the 68 without SRF (p = 0.022, hazard ratio 2.823,
      95% confidence interval [95% CI] 1.16, 6.85). Risk for ipsilateral SRE was
      unaffected by the presence of SRF among HRSFs (p = 0.561). Of low-risk patients
      with SRF, 33.3% experienced ipsilateral SRE, while those without SRF experienced
      no ipsilateral SRE (p < 0.001). CONCLUSION: Endoscopically determined stone
      clearance predicts disease recurrence within 5 years after RIRS. Even SRF are an
      important risk factor for future stone-related (ipsilateral) events; therefore,
      patients with residual fragments of any size should not be labeled "stone free"
      and endoscopic stone treatment should aim at complete stone clearance.

PMID- 27021948
TI  - Combating Frosting with Joule-Heated Liquid-Infused Superhydrophobic Coatings.
AB  - Frost formation is omnipresent when suitable environmental conditions are met. A
      good portion of research on combating frost formation has revolved around the
      passive properties of superhydrophobic (SHPO) and slippery lubricant-impregnated
      porous (SLIP) surfaces. Despite much progress, the need for surfaces that can
      effectively combat frost formation over prolonged periods still remains. In this
      work, we report, for the first time, the use of electrically conductive SHPO/SLIP
      surfaces for active mitigation of frost formation. First, we demonstrate the
      failure of these surfaces to passively avert prolonged (several hours) frosting.
      Next, we make use of their electroconductive property for active Joule heating,
      which results in the removal of any formed frost. We study the role of the
      impregnating lubricant in the heat transfer across the interface, the surface,
      and the ambient. We show that, even though the thermal properties of the
      impregnating lubricant may vary drastically, the lubricant type does not
      noticeably affect the defrosting behavior of the surface. We attribute this
      outcome to the dominant thermal resistance of the thick frost layer formed on the
      cooled surface. We support this claim by drawing parallels between the present
      system and heat transfer through a one-dimensional (1D) composite medium, and
      solving the appropriate transient transport equations. Lastly, we propose
      periodic thermal defrosting for averting frost formation altogether. This
      methodology utilizes the coating's passive repellent capabilities, while
      eliminating the dominant effect of thick deposited frost layers. The periodic
      heating approach takes advantage of lubricants with higher thermal
      conductivities, which effectively enhance heat transfer through the porous
      multiphase surface that forms the first line of defense against frosting.

PMID- 27021950
TI  - Handrub Consumption Mirrors Hand Hygiene Compliance.
AB  - We assessed handrub consumption as a surrogate marker for hand hygiene compliance
      from 2007 to 2014. Handrub consumption varied substantially between departments
      but correlated in a mixed effects regression model with the number of patient
      days and the observed hand hygiene compliance. Handrub consumption may supplement
      traditional hand hygiene observations. Infect Control Hosp Epidemiol 2016;37:707
      710.

PMID- 27021949
TI  - Treatment of Osteonecrosis in Children and Adolescents With Acute Lymphoblastic
      Leukemia.
AB  - BACKGROUND: Cure rates for acute lymphoblastic leukemia (ALL) have improved, but
      as therapy has intensified, the burden of osteonecrosis (ON) has increased.
      Limited data exist regarding surgical interventions for pediatric ALL patients
      with ON. MATERIALS AND METHODS: A multi-center cohort of children with newly
      diagnosed ALL was established with Pediatric Health Information System (PHIS)
      data from 43 freestanding children's hospitals from 1999 to 2011. Patients with
      ON identified by International Classification of Diseases, Ninth Revision (ICD-9)
      code were followed for up to 5 years after index ALL admission for the presence
      of ON-associated orthopedic surgical procedures. RESULTS: A cohort of 10,729 ALL
      patients was assembled, of which 242 (2.33%) were identified with an ICD-9 code
      for ON within 5 years of ALL diagnosis. Fifty-five patients (22.7%) with ON
      underwent orthopedic surgical intervention aimed at joint preservation (82%) or
      replacement (18%) with substantial practice variation by hospital in both the
      rate and type of surgical intervention. The majority of patients had surgical
      procedures while receiving maintenance therapy. None of the patients undergoing
      surgical intervention required intensive care unit-level care within 14 days of
      surgery, and there was no associated in-hospital mortality. CONCLUSIONS: No
      standard of care exists for treatment of ALL-associated ON. While considerable
      practice variation exists, surgical intervention appears relatively safe.

PMID- 27021951
TI  - The impact of stress on the structure of the adolescent brain: Implications for
      adolescent mental health.
AB  - Adolescent development is associated with major changes in emotional and
      cognitive functions, as well as a rise in stress-related psychological disorders
      such as anxiety and depression. It is also a time of significant maturation of
      the brain, marked by structural alterations in many limbic and cortical regions.
      Though many elegant human neuroimaging studies have described the adolescent
      related changes in these regions, relatively little is known about these changes
      in non-human animals. Moreover, both human and non-human data are lacking on how
      exposure to chronic stress may disrupt this structural maturation. Given the
      fundamental structure-function relationship in the nervous system, it will be
      important to understand how these normative and stress-induced structural
      alterations during adolescence influence psychological function, which in turn
      can modify future neural development. The purpose of this brief review is to
      describe the impact of stress on the structure of brain regions that continue to
      show structural maturation during adolescence and are highly sensitive to the
      effects of chronic stress exposure. Specifically, this review will focus on the
      amygdala, hippocampal formation, and prefrontal cortex, particularly from a
      morphological perspective. As many unanswered questions remain in this area of
      investigation, potential future lines of research are also discussed. A deeper
      appreciation of how stress affects adolescent brain development will be needed if
      we are to gain a better understanding of the mechanisms that mediate the increase
      in stress-related psychological dysfunctions often observed during this stage of
      development. This article is part of a Special Issue entitled SI: Adolescent
      plasticity.

PMID- 27021952
TI  - Transcriptional activity of acetylcholinesterase gene is regulated by DNA
      methylation during C2C12 myogenesis.
AB  - The expression of acetylcholinesterase (AChE), an enzyme hydrolyzes
      neurotransmitter acetylcholine at vertebrate neuromuscular junction, is regulated
      during myogenesis, indicating the significance of muscle intrinsic factors in
      controlling the enzyme expression. DNA methylation is essential for temporal
      control of myogenic gene expression during myogenesis; however, its role in AChE
      regulation is not known. The promoter of vertebrate ACHE gene carries highly
      conserved CG-rich regions, implying its likeliness to be methylated for
      epigenetic regulation. A DNA methyltransferase inhibitor, 5-azacytidine (5-Aza),
      was applied onto C2C12 cells throughout the myotube formation. When DNA
      methylation was inhibited, the promoter activity, transcript expression and
      enzymatic activity of AChE were markedly increased after day 3 of
      differentiation, which indicated the putative role of DNA methylation. By
      bisulfite pyrosequencing, the overall methylation rate was found to peak at day 3
      during C2C12 cell differentiation; a SP1 site located at -1826bp upstream of
      mouse ACHE gene was revealed to be heavily methylated. The involvement of
      transcriptional factor SP1 in epigenetic regulation of AChE was illustrated here:
      (i) the SP1-driven transcriptional activity was increased in 5-Aza-treated C2C12
      culture; (ii) the binding of SP1 onto the SP1 site of ACHE gene was fully blocked
      by the DNA methylation; and (iii) the sequence flanking SP1 sites of ACHE gene
      was precipitated by chromatin immuno-precipitation assay. The findings suggested
      the role of DNA methylation on AChE transcriptional regulation and provided
      insight in elucidating the DNA methylation-mediated regulatory mechanism on AChE
      expression during muscle differentiation.

PMID- 27021953
TI  - Life-long music practice and executive control in older adults: An event-related
      potential study.
AB  - Recent research has indicated that music practice can influence cognitive
      processing across the lifespan. Although extensive musical experience may have a
      mitigating effect on cognitive decline in older adults, the nature of changes to
      brain functions underlying performance benefits remains underexplored. The
      present study was designed to investigate the underlying neural mechanisms that
      may support apparent beneficial effects of life-long musical practice on
      cognition. We recorded event-related potentials (ERPs) in older musicians (N=17;
      average age=69.2) and non-musicians (N=17; average age=69.9), matched for age and
      education, while they completed an executive control task (visual go/no-go).
      Whereas both groups showed similar response speed and accuracy on go trials,
      older musicians showed fewer no-go errors. ERP recordings revealed the typical
      N2/P3 complex, but the nature of these responses differed between groups in that
      (1) older musicians showed larger N2 and P3 effects ('no-go minus go' amplitude),
      with the N2 amplitude being correlated with behavioral accuracy for no-go trials
      and (2) the topography of the P3 response was more anterior in musicians.
      Moreover, P3 amplitude was correlated with measures of musical experience in
      musicians. In our discussion of these results, we propose that music practice may
      have conferred an executive control advantage for musicians in later life.

PMID- 27021954
TI  - Alterations in the expression of Per1 and Per2 induced by Abeta31-35 in the
      suprachiasmatic nucleus, hippocampus, and heart of C57BL/6 mouse.
AB  - Patients with Alzheimer's disease (AD) have circadian rhythm disorders, which are
      mimicked in 3xTg-AD and 5xFAD mouse models. The deposition of beta-amyloid
      protein (Abeta) is an important pathological characteristic of AD, however, its
      role in inducing alterations in biological rhythms and in the expression of
      circadian clock-related genes remains elusive. The Per1 and Per2 play complex
      regulatory roles in biological clocks and are diffusely expressed in the
      suprachiasmatic nucleus (SCN), hippocampus and heart. In the present study, wheel
      running behavioral experiments showed that Abeta31-35, which was administered
      into the hippocampus, resulted in the disruption of the circadian rhythm of
      C57BL/6 mice. Furthermore, real-time PCR and western blot analysis showed that
      Abeta31-35 altered the expression of the Per1 and Per2 in the SCN, hippocampus
      and heart. These findings provide experimental evidence for circadian rhythm
      disturbances in patients with AD.

PMID- 27021955
TI  - Ethanol preconditioning of rat cerebellar cultures targets NMDA receptors to the
      synapse and enhances peroxiredoxin 2 expression.
AB  - Epidemiological studies indicate that light-moderate alcohol (ethanol) consumers
      tend to have reduced risks of cognitive impairment and progression to dementia
      during aging. Exploring possible mechanisms, we previously found that moderate
      ethanol preconditioning (MEP, 20-30mM) of rat brain cultures for several days
      instigated neuroprotection against beta-amyloid peptides. Our biochemical
      evidence implicated the NMDA receptor (NMDAR) as a potential neuroprotective
      "sensor", specifically via synaptic NMDAR signaling. It remains unclear how
      ethanol modulates the receptor and its downstream targets to engender
      neuroprotection. Here we confirm with deconvolution microscopy that MEP of rat
      mixed cerebellar cultures robustly increases synaptic NMDAR localization. Phospho
      activation of the non-receptor tyrosine kinases Src and Pyk2, known to be linked
      to synaptic NMDAR, is also demonstrated. Additionally, the preconditioning
      enhances levels of an antioxidant protein, peroxiredoxin 2 (Prx2), reported to be
      downstream of synaptic NMDAR signaling, and NMDAR antagonism with memantine
      (earlier found to abrogate MEP neuroprotection) blocks the Prx2 elevations. To
      further link Prx2 with antioxidant-based neuroprotection, we circumvented the
      ethanol preconditioning-NMDAR pathway by pharmacologically increasing Prx2 with
      the naturally-occurring cruciferous compound, 3H-1,2-dithiole-3-thione (D3T).
      Thus, D3T pretreatment elevated Prx2 expression to a similar extent as MEP, while
      concomitantly preventing beta-amyloid neurotoxicity; D3T also protected the
      cultures from hydrogen peroxide toxicity. The findings support a mechanism that
      couples synaptic NMDAR signaling, Prx2 expression and augmented antioxidant
      defenses in ethanol preconditioning-induced neuroprotection. That this mechanism
      can be emulated by a cruciferous vegetable constituent suggests that such
      naturally-occurring "neutraceuticals" may be useful in therapy for oxidative
      stress-related dementias.

PMID- 27021956
TI  - The UPR and synaptic dysfunction in neurodegeneration.
AB  - Activation of the unfolded protein response (UPR) is emerging as a common theme
      in neurodegenerative diseases, seen in both human brain tissue and mouse models.
      Genetic and pharmacological manipulation of the pathway in several mouse models
      has shown that this is not a passive consequence of the neurodegeneration
      process. Rather, over-activation of the PERK branch of the UPR directly
      contributes to disease pathogenesis through the critical reduction in neuronal
      protein synthesis rates via the phosphorylation of eIF2alpha. eIF2alpha-P levels
      are critical to learning and memory in health also; the sustained high levels in
      neurodegenerative disease results both in impaired learning and memory and to
      loss of synapse numbers and function essential for neuronal survival.
      Pharmacological inhibition of this process is strikingly neuroprotective in
      several models, leading to the discovery of the first small molecule to prevent
      neurodegeneration in vivo. Critically, this represents a generic approach for
      boosting memory and the prevention of neurodegeneration through rescue of
      synapses across the spectrum of these disorders, with few exceptions, independent
      of disease-specific proteins. Targeting the UPR, and particularly eIF2alpha-P
      mediated translational failure is emerging as a compelling strategy for rescuing
      synaptic failure and neuronal loss for new treatments for dementia and
      neurodegenerative disease. This article is part of a Special Issue entitled SI:ER
      stress.

PMID- 27021957
TI  - Human xanthine oxidase recombinant in E. coli: A whole cell catalyst for
      preparative drug metabolite synthesis.
AB  - Human xanthine oxidoreductase (XOR), which is responsible for the final steps of
      the purine metabolism pathway and involved in oxidative drug metabolism, was
      successfully expressed in Escherichia coli BL21(DE3) Gold. Recombinant human (rh)
      XOR yielded higher productivity with the gene sequence optimized for expression
      in E.coli than with the native gene sequence. Induction of XOR expression with
      lactose or IPTG resulted in complete loss of activity whereas shake flasks
      cultures using media rather poor in nutrients resulted in functional XOR
      expression in the stationary phase. LB medium was used for a 25L fermentation in
      fed-batch mode, which led to a 5 fold increase of the enzyme productivity when
      compared to cultivation in shake flasks. Quinazoline was used as a substrate on
      the semi-preparative scale using an optimized whole cell biotransformation
      protocol, yielding 73mg of the isolated product, 4-quinazolinone, from 104mg of
      starting material. 

PMID- 27021958
TI  - Aims and methods of biosteganography.
AB  - Applications of biotechnology to information security are now possible and have
      potentially far reaching political and technological implications. This change in
      information security practices, initiated by advancements in molecular biological
      and biotechnology, warrants reasonable and widespread consideration by
      biologists, biotechnologists and philosophers. I offer an explication of the
      landmark contributions, developments and current possibilities of
      biosteganography-the process of transmitting secure messages via biological
      mediums. I address, (i) how information can be stored and encoded in biological
      mediums, (ii) how biological mediums (e.g. DNA, RNA, protein) and storage systems
      (e.g. cells, biofilms, organisms) influence the nature of information security,
      and (iii) what constitutes a viable application of such biotechnologies. 

PMID- 27021959
TI  - Optimization of peptide nucleic acid fluorescence in situ hybridization (PNA
      FISH) for the detection of bacteria: The effect of pH, dextran sulfate and probe
      concentration.
AB  - Fluorescence in situ hybridization (FISH) is a molecular technique widely used
      for the detection and characterization of microbial populations. FISH is affected
      by a wide variety of abiotic and biotic variables and the way they interact with
      each other. This is translated into a wide variability of FISH procedures found
      in the literature. The aim of this work is to systematically study the effects of
      pH, dextran sulfate and probe concentration in the FISH protocol, using a general
      peptide nucleic acid (PNA) probe for the Eubacteria domain. For this, response
      surface methodology was used to optimize these 3 PNA-FISH parameters for Gram
      negative (Escherichia coli and Pseudomonas fluorescens) and Gram-positive species
      (Listeria innocua, Staphylococcus epidermidis and Bacillus cereus). The obtained
      results show that a probe concentration higher than 300nM is favorable for both
      groups. Interestingly, a clear distinction between the two groups regarding the
      optimal pH and dextran sulfate concentration was found: a high pH (approx. 10),
      combined with lower dextran sulfate concentration (approx. 2% [w/v]) for Gram
      negative species and near-neutral pH (approx. 8), together with higher dextran
      sulfate concentrations (approx. 10% [w/v]) for Gram-positive species. This
      behavior seems to result from an interplay between pH and dextran sulfate and
      their ability to influence probe concentration and diffusion towards the rRNA
      target. This study shows that, for an optimum hybridization protocol, dextran
      sulfate and pH should be adjusted according to the target bacteria. 

PMID- 27021960
TI  - Exploration of a haloarchaeon, Halostagnicola larsenii, isolated from rock pit
      sea water, West Coast of Maharashtra, India, for the production of
      bacteriorhodopsin.

PMID- 27021961
TI  - Mechanism of oxidative conversion of Amplex(r) Red to resorufin: Pulse radiolysis
      and enzymatic studies.
AB  - Amplex(r) Red (10-acetyl-3,7-dihydroxyphenoxazine) is a fluorogenic probe widely
      used to detect and quantify hydrogen peroxide in biological systems. Detection of
      hydrogen peroxide is based on peroxidase-catalyzed oxidation of Amplex(r) Red to
      resorufin. In this study we investigated the mechanism of one-electron oxidation
      of Amplex(r) Red and we present the spectroscopic characterization of transient
      species formed upon the oxidation. Oxidation process has been studied by a pulse
      radiolysis technique with one-electron oxidants (N3(*), CO3(*-),(*)NO2 and
      GS(*)). The rate constants for the Amplex(r) Red oxidation by N3(*)
      ((2)k=2.1.10(9)M(-1)s(-1), at pH=7.2) and CO3(*-) ((2)k=7.6.10(8)M(-1)s(-1), at
      pH=10.3) were determined. Two intermediates formed during the conversion of
      Amplex(r) Red into resorufin have been characterized. Based on the results
      obtained, the mechanism of transformation of Amplex(r) Red into resorufin,
      involving disproportionation of the Amplex(r) Red-derived radical species, has
      been proposed. The results indicate that peroxynitrite-derived radicals, but not
      peroxynitrite itself, are capable to oxidize Amplex(r) Red to resorufin. We also
      demonstrate that horseradish peroxidase can catalyze oxidation of Amplex(r) Red
      not only by hydrogen peroxide, but also by peroxynitrite, which needs to be
      considered when employing the probe for hydrogen peroxide detection.

PMID- 27021962
TI  - Synthesis, evaluation, and metabolism of novel [6]-shogaol derivatives as potent
      Nrf2 activators.
AB  - Oxidative stress is a central component of many chronic diseases. The Kelch-like
      ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 p45-related factor 2
      (Nrf2) system is a major regulatory pathway of cytoprotective genes against
      oxidative and electrophilic stress. Activation of the Nrf2 pathway plays crucial
      roles in the chemopreventive effects of various inducers. In this study, we
      developed a novel class of potent Nrf2 activators derived from ginger compound,
      [6]-shogaol (6S), using the Tg[glutathione S-transferase pi 1 (gstp1):green
      fluorescent protein (GFP)] transgenic zebrafish model. Investigation of structure
      activity relationships of 6S derivatives indicates that the combination of an
      alpha,beta-unsaturated carbonyl entity and a catechol moiety in one compound
      enhances the Tg(gstp1:GFP) fluorescence signal in zebrafish embryos. Chemical
      reaction and in vivo metabolism studies of the four most potent 6S derivatives
      showed that both alpha,beta-unsaturated carbonyl entity and catechol moiety act
      as major active groups for conjugation with the sulfhydryl groups of the cysteine
      residues. In addition, we further demonstrated that 6S derivatives increased the
      expression of Nrf2 downstream target, heme oxygenase-1, in both a dose- and time
      dependent manner. These results suggest that alpha,beta-unsaturated carbonyl
      entity and catechol moiety of 6S derivatives may react with the cysteine residues
      of Keap1, disrupting the Keap1-Nrf2 complex, thereby liberating and activating
      Nrf2. Our findings of natural product-derived Nrf2 activators lead to design
      options of potent Nrf2 activators for further optimization.

PMID- 27021963
TI  - Exercise training as a drug to treat age associated frailty.
AB  - Exercise causes an increase in the production of free radicals [1]. As a result
      of a hormetic mechanism antioxidant enzymes are synthesised and the cells are
      protected against further oxidative stress. Thus, exercise can be considered as
      an antioxidant [2]. Age-associated frailty is a major medical and social concern
      as it can easily lead to dependency. In this review we describe that oxidative
      stress is associated with frailty and the mechanism by which exercise prevents
      age-associated frailty. We propose that individually tailored multicomponent
      exercise programmes are one of the best ways to prevent and to treat age
      associated frailty.

PMID- 27021964
TI  - Exercise-induced ROS in heat shock proteins response.
AB  - Cells have evolved multiple and sophisticated stress response mechanisms aiming
      to prevent macromolecular (including proteins, lipids, and nucleic acids) damage
      and to maintain or re-establish cellular homeostasis. Heat shock proteins (HSPs)
      are among the most highly conserved, ubiquitous, and abundant proteins in all
      organisms. Originally discovered more than 50 years ago through heat shock
      stress, they display multiple, remarkable roles inside and outside cells under a
      variety of stresses, including also oxidative stress and radiation, recognizing
      unfolded or misfolded proteins and facilitating their restructuring. Exercise
      consists in a combination of physiological stresses, such as metabolic
      disturbances, changes in circulating levels of hormones, increased temperature,
      induction of mild to severe inflammatory state, increased production of reactive
      oxygen and nitrogen species (ROS and RNS). As a consequence, exercise is one of
      the main stimuli associated with a robust increase in different HSPs in several
      tissues, which appears to be also fundamental in facilitating the cellular
      remodeling processes related to the training regime. Among all factors involved
      in the exercise-related modulation of HSPs level, the ROS production in the
      contracting muscle or in other tissues represents one of the most attracting, but
      still under discussion, mechanism. Following exhaustive or damaging muscle
      exercise, major oxidative damage to proteins and lipids is likely involved in HSP
      expression, together with mechanically induced damage to muscle proteins and the
      inflammatory response occurring several days into the recovery period. Instead,
      the transient and reversible oxidation of proteins by physiological
      concentrations of ROS seems to be involved in the activation of stress response
      following non-damaging muscle exercise. This review aims to provide a critical
      update on the role of HSPs response in exercise-induced adaptation or damage in
      humans, focusing on experimental results where the link between redox homeostasis
      and HSPs expression by exercise has been addressed. Further, with the support of
      in vivo and in vitro studies, we discuss the putative molecular mechanisms
      underlying the ROS-mediated modulation of HSP expression and/or activity during
      exercise.

PMID- 27021965
TI  - A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans
      resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages.
AB  - Resveratrol gains a great interest for its strong antioxidant properties, while
      the molecular mechanisms underlie the beneficial effects on psychosocial stress
      remain controversial. In this study, we demonstrated that resveratrol protected
      peritoneal macrophages and RAW 264.7 cells from stress-induced decrease in the
      total cell count, phagocytic capability, reactive oxygen species generation,
      monodansylcadaverine and mitochondrial membrane potential in stressed mice.
      Resveratrol promoted stress-induced autophagy in both models. Modulation of
      autophagy by rapamycin or 3-methyladenine regulated the protective effect of
      resveratrol, suggesting a role of autophagy in the protective mechanisms of
      resveratrol. The comparison studies revealed that distinct mechanisms were
      implicated in the protective effect of resveratrol and other antioxidants
      (vitamin C and edaravone). Resveratrol promoted autophagy via upregulating SIRT3
      expression and phosphorylation of AMP-activated protein kinase (AMPK). Knockdown
      of SIRT3 resulted in decreased autophagy and abolished protective effect of
      resveratrol. SIRT1 was also involved in the protective mechanism of resveratrol,
      although its effect on autophagy was unnoticeable. Pharmacological manipulation
      of autophagy modulated the effects of resveratrol on SIRT3 and AMPK, revealing
      the engagement of a positive feedback loop. In sharp contrast, vitamin C and
      edaravone effectively protected macrophages from stress-induced cytotoxicity,
      accompanied by downregulated SIRT3 expression and AMPK phosphorylation, and
      decreased level of autophagy response. Taken together, we conclude that a
      SIRT3/AMPK/autophagy network orchestrates in the protective effect of resveratrol
      in macrophages.

PMID- 27021966
TI  - Caveolin-1 protects against hepatic ischemia/reperfusion injury through
      ameliorating peroxynitrite-mediated cell death.
AB  - Nitrative stress is considered as an important pathological process of hepatic
      ischemia and reperfusion injury but its regulating mechanisms are largely
      unknown. In this study, we tested the hypothesis that caveolin-1 (Cav-1), a
      plasma membrane scaffolding protein, could be an important cellular signaling
      against hepatic I/R injury through inhibiting peroxynitrite (ONOO(-))-induced
      cellular damage. Male wild-type mice and Cav-1 knockout (Cav-1(-/-)) were
      subjected to 1h hepatic ischemia following 1, 6 and 12h of reperfusion by
      clipping and releasing portal vessels respectively. Immortalized human hepatocyte
      cell line (L02) was subjected to 1h hypoxia and 6h reoxygenation and treated with
      Cav-1 scaffolding domain peptide. The major discoveries included: (1) the
      expression of Cav-1 in serum and liver tissues of wild-type mice was time
      dependently elevated during hepatic ischemia-reperfusion injury. (2) Cav-1
      scaffolding domain peptide treatment inhibited cleaved caspase-3 expression in
      the hypoxia-reoxygenated L02 cells; (3) Cav-1 knockout (Cav-1(-/-)) mice had
      significantly higher levels of serum transaminases (ALT&AST) and TNF-alpha, and
      higher rates of apoptotic cell death in liver tissues than wild-type mice after
      subjected to 1h hepatic ischemia and 6hour reperfusion; (4) Cav-1(-/-) mice
      revealed higher expression levels of iNOS, ONOO(-) and 3-nitrotyrosine (3-NT) in
      the liver than wild-type mice, and Fe-TMPyP, a representative peroxynitrite
      decomposition catalyst (PDC), remarkably reduced level of ONOO(-) and 3-NT and
      ameliorated the serum ALT, AST and TNF-alpha levels in both wild-type and Cav-1(
      /-) mice. Taken together, we conclude that Cav-1 could play a critical role in
      preventing nitrative stress-induced liver damage during hepatic ischemia
      reperfusion injury.

PMID- 27021967
TI  - Factors Related to Early Clinical Effects of Quetiapine Extended-Release: A
      Multinational, Prospective, Observational Study.
AB  - BACKGROUND AND OBJECTIVES: The first weeks of treatment with antipsychotics are
      important for the development of their long-term efficacy. The objective of this
      study was to identify factors related to early clinical effects and quality of
      life (QoL) improvements with quetiapine extended-release (XR). METHODS: Six
      hundred and sixty-five patients starting with quetiapine XR were followed up for
      8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252,
      other psychiatric conditions = 60). Clinical effects were assessed by the
      Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog
      scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse
      events were explored: movement disorders by the UKU and Simpson-Angus scales,
      weight gain by calibrated balances, and diurnal somnolence by the Epworth
      Somnolence Scale (ESS). RESULTS: The mean dose of quetiapine XR during follow-up
      was 195.6 +/- 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week
      8 by 2.7 +/- 0.1 points and 25.1 +/- 0.9 points. Adverse events were observed in
      34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction
      in ESS score was also observed at week 8. Factors independently associated with
      change in QoL-VAS >=20 points (n = 292, 43 %) were female gender, more severe
      disease at baseline, higher antipsychotic dose during follow-up, and improvements
      in somnolence. Factors independently associated with clinically significant
      improvement (CGI-C >=5, n = 610, 93 %) were greater change in QoL-VAS, less
      frequent movement disorders at baseline, and lack of adverse events during follow
      up, especially somnolence. CONCLUSIONS: Results from this real-setting, large
      observational study in Central America suggest that disease severity at baseline,
      gender, antipsychotic dose, and occurrence of adverse reactions has a significant
      impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov
      registration number NCT02409823.

PMID- 27021968
TI  - Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration
      of Efficacy.
AB  - Lisdexamfetamine dimesylate (LDX) is a long-acting d-amphetamine prodrug used to
      treat attention-deficit/hyperactivity disorder (ADHD) in children, adolescents
      and adults. LDX is hydrolysed in the blood to yield d-amphetamine, and the
      pharmacokinetic profile of d-amphetamine following oral administration of LDX has
      a lower maximum plasma concentration (Cmax), extended time to Cmax (Tmax) and
      lower inter- and intra-individual variability in exposure compared with the
      pharmacokinetic profile of an equivalent dose of immediate-release (IR) d
      amphetamine. The therapeutic action of LDX extends to at least 13 h post-dose in
      children and 14 h post-dose in adults, longer than that reported for any other
      long-acting formulation. Drug-liking scores for LDX are lower than for an
      equivalent dose of IR d-amphetamine, which may result from the reduced
      euphorigenic potential associated with its pharmacokinetic profile. These
      pharmacokinetic and pharmacodynamic characteristics of LDX may be beneficial in
      the management of symptoms in children, adolescents and adults with ADHD.

PMID- 27021970
TI  - Control strategies of 3-cell Central Pattern Generator via global stimuli.
AB  - The study of the synchronization patterns of small neuron networks that control
      several biological processes has become an interesting growing discipline. Some
      of these synchronization patterns of individual neurons are related to some
      undesirable neurological diseases, and they are believed to play a crucial role
      in the emergence of pathological rhythmic brain activity in different diseases,
      like Parkinson's disease. We show how, with a suitable combination of short and
      weak global inhibitory and excitatory stimuli over the whole network, we can
      switch between different stable bursting patterns in small neuron networks (in
      our case a 3-neuron network). We develop a systematic study showing and
      explaining the effects of applying the pulses at different moments. Moreover, we
      compare the technique on a completely symmetric network and on a slightly
      perturbed one (a much more realistic situation). The present approach of using
      global stimuli may allow to avoid undesirable synchronization patterns with
      nonaggressive stimuli. 

PMID- 27021969
TI  - Electronic Structure of the Ferryl Intermediate in the alpha-Ketoglutarate
      Dependent Non-Heme Iron Halogenase SyrB2: Contributions to H Atom Abstraction
      Reactivity.
AB  - Low temperature magnetic circular dichroism (LT MCD) spectroscopy in combination
      with quantum-chemical calculations are used to define the electronic structure
      associated with the geometric structure of the Fe(IV)?O intermediate in SyrB2
      that was previously determined by nuclear resonance vibrational spectroscopy.
      These studies elucidate key frontier molecular orbitals (FMOs) and their
      contribution to H atom abstraction reactivity. The VT MCD spectra of the
      enzymatic S = 2 Fe(IV)?O intermediate with Br(-) ligation contain information
      rich features that largely parallel the corresponding spectra of the S = 2 model
      complex (TMG3tren)Fe(IV)?O (Srnec, M.; Wong, S. D.; England, J; Que, L; Solomon,
      E. I. Proc. Natl. Acad. Sci. USA 2012, 109, 14326-14331). However, quantitative
      differences are observed that correlate with pi-anisotropy and oxo donor strength
      that perturb FMOs and affect reactivity. Due to pi-anisotropy, the Fe(IV)?O
      active site exhibits enhanced reactivity in the direction of the substrate cavity
      that proceeds through a pi-channel that is controlled by perpendicular
      orientation of the substrate C-H bond relative to the halide-Fe(IV)?O plane.
      Also, the increased intrinsic reactivity of the SyrB2 intermediate relative to
      the ferryl model complex is correlated to a higher oxyl character of the Fe(IV)?O
      at the transition states resulting from the weaker ligand field of the
      halogenase. 

PMID- 27021972
TI  - PSA ANNUAL MEETING 2011.

PMID- 27021971
TI  - DNA damage is a late event in resveratrol-mediated inhibition of Escherichia
      coli.
AB  - Resveratrol is an important phytoalexin notable for a wide variety of beneficial
      activities. Resveratrol has been reported to be active against various pathogenic
      bacteria. However, it is not clear at the molecular level how this important
      activity is manifested. Resveratrol has been reported to bind to cupric ions and
      reduce it. In the process, it generates copper-peroxide complex and reactive
      oxygen species (ROS). Due to this ability, resveratrol has been shown to cleave
      plasmid DNA in several studies. To this end, we envisaged DNA damage to play a
      role in resveratrol mediated inhibition in Escherichia coli. We employed DNA
      damage repair deficient mutants from keio collection to demonstrate the
      hypersensitive phenotype upon resveratrol treatment. Analysis of integrity and
      PCR efficiency of plasmid DNA from resveratrol-treated cells revealed significant
      DNA damage after 6 h or more compared to DNA from vehicle-treated cells. RAPD-PCR
      was performed to demonstrate the damage in genomic DNA from resveratrol-treated
      cells. In addition, in situ DNA damage was observed under fluorescence microscopy
      after resveratrol treatment. Further resveratrol treatment resulted in cell cycle
      arrest of significant fraction of population revealed by flow cytometry. However,
      a robust induction was not observed in phage induction assay and induction of DNA
      damage response genes quantified by promoter fused fluorescent tracker protein.
      These observations along with our previous observation that resveratrol induces
      membrane damage in E. coli at early time point reveal, DNA damage is a late
      event, occurring after a few hours of treatment. 

PMID- 27021973
TI  - GENETIC POPULATION STRUCTURE AND MATING SYSTEM IN CHONDRUS CRISPUS (RHODOPHYTA)1.
AB  - Chondrus crispus Stackh. has been intensely studied, yet no study to date has
      elucidated its population structure or mating system despite many populations in
      which there was a haploid bias and lack of male gametophytes. Therefore, 12
      nuclear microsatellite loci were identified in this red alga. Microsatellite
      markers were developed and tested against a panel of specimens collected from two
      shore levels at two sites in Brittany, France: Pointe de Primel and Pointe de la
      Jument, Concarneau. Single locus genetic determinism was verified at eight
      polymorphic loci, as only one band was observed for haploid genotypes, whereas
      one or two bands were observed for diploids. These markers enabled the detection
      of unique genotypes within sampled populations, indicating that very few fronds
      shared the same multilocus genotype. This finding suggests that asexual
      reproduction was not the prevailing mode of reproduction. In addition, we
      explored the hierarchical population structure showing that gene flow is
      restricted at small spatial scales (<50 m) between upper and lower Chondrus-range
      populations within a shore. Sexual reproduction predominated in the populations
      of C. crispus studied, but probably due to fine-scale spatial substructuring,
      inbreeding was also significant. In conclusion, this study reveals that fine
      scale genetic variation is of major importance in C. crispus, suggesting that
      differences between microhabitats should be essential in understanding
      evolutionary processes in this species.

PMID- 27021974
TI  - PHENOTYPIC DIFFERENTIATION AT SOUTHERN LIMIT BORDERS: THE CASE STUDY OF TWO
      FUCOID MACROALGAL SPECIES WITH DIFFERENT LIFE-HISTORY TRAITS1.
AB  - Marginal populations are often geographically isolated, smaller, and more
      fragmented than central populations and may frequently have to face suboptimal
      local environmental conditions. Persistence of these populations frequently
      involves the development of adaptive traits at phenotypic and genetic levels. We
      compared population structure and demographic variables in two fucoid macroalgal
      species contrasting in patterns of genetic diversity and phenotypic plasticity at
      their southern distribution limit with a more central location. Models were
      Ascophyllum nodosum (L.) Le Jol. (whose extreme longevity and generation overlap
      may buffer genetic loss by drift) and Fucus serratus L. (with low genetic
      diversity at southern margins). At edge locations, both species exhibited trends
      in life-history traits compatible with population persistence but by using
      different mechanisms. Marginal populations of A. nodosum had higher reproductive
      output in spite of similar mortality rates at all life stages, making edge
      populations denser and with smaller individuals. In F. serratus, rather than
      demographic changes, marginal populations differed in habitat, occurring
      restricted to a narrower vertical habitat range. We conclude that persistence of
      both A. nodosum and F. serratus at the southern-edge locations depends on
      different strategies. Marginal population persistence in A. nodosum relies on a
      differentiation in life-history traits, whereas F. serratus, putatively poorer in
      evolvability potential, is restricted to a narrower vertical range at border
      locations. These results contribute to the general understanding of mechanisms
      that lead to population persistence at distributional limits and to predict
      population resilience under a scenario of environmental change.

PMID- 27021975
TI  - ABIOTIC REGULATION OF INVESTMENT IN SEXUAL VERSUS VEGETATIVE REPRODUCTION IN THE
      CLONAL KELP LAMINARIA SINCLAIRII (LAMINARIALES, PHAEOPHYCEAE)1.
AB  - Clonal kelp taxa may reproduce both sexually and vegetatively resulting in a
      potential trade-off in the allocation of acquired carbon and nitrogen resources.
      Such trade-offs may dictate a different response of clonal kelps to varying
      environmental conditions relative to aclonal kelp taxa. Laboratory temperature
      and nutrient manipulation experiments demonstrated that investment in sexual and
      vegetative reproduction in Laminaria sinclairii (Harv. ex Hook. f. et Harv.)
      Farl., C. L. Anderson et D. C. Eaton was regulated by different abiotic factors.
      Sorus production (investment in sexual reproduction) and blade growth were
      significantly higher at 12 degrees C compared to 17 degrees C, regardless of
      nutrient concentration. Net carbon storage and depletion in rhizomes were
      observed in the low- and high-temperature treatments, respectively, suggesting
      that carbon stores were not responsible for increased growth. Rhizome elongation
      (investment in vegetative reproduction), on the other hand, was significantly
      higher in 12 MUM NO3- than in 2 MUM NO3- , irrespective of temperature. This
      increase in rhizome growth was concurrent with elevated rhizome percent tissue
      nitrogen levels also observed in treatments with higher nutrients, again
      indicating a growth response to treatment independent of previous nutrient
      stores. These results suggest that regulation of growth and investment in sexual
      reproduction in L. sinclairii is similar to that in aclonal kelps (i.e., warmer
      temperatures result in decreased reproductive output). Additionally, depletion of
      carbon and nitrogen from rhizomes in suboptimal conditions confirms the role of
      clonal kelp rhizomes in carbon and nutrient storage.

PMID- 27021976
TI  - THE POTENTIAL INDICATOR VALUE OF RARE TAXA RICHNESS IN DIATOM-BASED STREAM
      BIOASSESSMENT1.
AB  - Despite their recognized contribution to species richness, the importance of rare
      taxa richness in bioassessment is unclear. This study aimed to characterize the
      environmental factors affecting the number of rare diatom taxa in western U.S.
      streams and rivers, and to evaluate whether this number can be used to
      differentiate streams with contrasting human disturbance. Three different
      categories of rare taxa were used: satellite (taxa with low occurrence and low
      abundance), rural (taxa with high occurrence and low abundance), and urban (taxa
      with low occurrence and high abundance). Common taxa were included as a separate
      category of core taxa (taxa with high occurrence and high abundance). We analyzed
      987 diatom samples collected over the period of 5 years (2000-2004) for the U.S.
      Environmental Protection Agency's (EPA) Western Environmental Monitoring and
      Assessment Program (WEMAP). The results showed that rural taxa richness (number
      of rural taxa per site) increased along a longitudinal gradient from mountainous,
      fast-flowing oligotrophic streams with fewer fine substrates to large, slow
      moving, nutrient-rich rivers with abundance of fine substrates. Rural taxa
      richness was the only rarity metric that distinguished least disturbed
      (reference) sites from the most disturbed (impacted) sites, but it was
      significantly different only in the mountains ecoregion. Core taxa richness
      distinguished reference from impacted sites in the West and in each one of the
      three ecoregions (mountains, plains, and xeric). Our findings revealed that rural
      taxa richness can be used as an indicator of human disturbance in streams/rivers,
      especially in the mountains ecoregion, and that rarity definition is important in
      bioassessment.

PMID- 27021977
TI  - RAPID NITRATE UPTAKE RATES AND LARGE SHORT-TERM STORAGE CAPACITIES MAY EXPLAIN
      WHY OPPORTUNISTIC GREEN MACROALGAE DOMINATE SHALLOW EUTROPHIC ESTUARIES1.
AB  - We quantified the effects of initial macroalgal tissue nitrogen (N) status
      (depleted and enriched) and varying pulses of nitrate (NO3- ) concentration on
      uptake and storage of nitrogen in Ulva intestinalis L. and Ulva expansa (Setch.)
      Setch. et N. L. Gardner using mesocosms modeling shallow coastal estuaries in
      Mediterranean climates. Uptake of NO3- (MUmol . g dry weight [dwt]-1  . h-1 ) was
      measured as loss from the water after 1, 2, 4, 8, 12, and 24 h and storage as
      total tissue nitrogen (% dwt) and nitrate (ppm). Both species of algae exhibited
      a high affinity for NO3- across all N pulses and initial tissue contents. There
      was greater NO3- removal from the water for depleted than enriched algae across
      all time intervals. In the low-N-pulse treatment, U. intestinalis and U. expansa
      removed all measurable NO3- within 8 and 12 h, respectively, and in the medium
      and high treatments, removal was high and then decreased over time. Maximum mean
      uptake rates of nitrate were greater for U. expansa (~300 MUmol . g dwt-1  . h-1
      ) than U. intestinalis (~100 MUmol . g dwt-1  . h-1 ); however, uptake rates were
      highly variable over time. Overall, U. expansa uptake rates were double those of
      U. intestinalis. Maximum tissue NO3- for U. expansa was >1,000 ppm, five times
      that of U. intestinalis, suggesting that U. expansa has a greater storage
      capacity in this cellular pool. These results showed that opportunistic green
      algae with differing tissue nutrient histories were able to efficiently remove
      nitrate from the water across a wide range of N pulses; thus, both are highly
      adapted to proliferate in estuarine environments with pulsed nutrient supplies.

PMID- 27021978
TI  - EVALUATION OF ENVIRONMENTAL FACTORS ON CYANOBACTERIAL BLOOM IN EUTROPHIC
      RESERVOIR USING ARTIFICIAL NEURAL NETWORKS1.
AB  - Cyanobacterial blooms are a common issue in eutrophic freshwaters, and some
      cyanobacteria produce toxins, threatening the health of humans and livestock.
      Microcystin, a representative cyanobacterial hepatotoxin, is frequently detected
      in most Korean lakes and reservoirs. This study developed predictive models for
      cyanobacterial bloom using artificial neural networks (ANNs; self-organizing map
      [SOM] and multilayer perceptron [MLP]), including an evaluation of related
      environmental factors. Fourteen environmental factors, as independent variables
      for predicting the cyanobacteria density, were measured weekly in the Daechung
      Reservoir from spring to autumn over 5 years (2001, 2003-2006). Cyanobacterial
      density was highly associated with environmental factors measured 3 weeks
      earlier. The SOM model was efficient in visualizing the relationships between
      cyanobacteria and environmental factors, and also for tracing temporal change
      patterns in the environmental condition of the reservoir. And the MLP model
      exhibited a good predictive power for the cyanobacterial density, based on the
      environmental factors of 3 weeks earlier. The water temperature and total
      dissolved nitrogen were the major determinants for cyanobacteria. The water
      temperature had a stronger influence on cyanobacterial growth than the nutrient
      concentrations in eutrophic waters. Contrary to general expectations, the
      nitrogen compounds played a more important role in bloom formation than the
      phosphorus compounds.

PMID- 27021979
TI  - VARIATIONS IN GROWTH, EROSION, PRODUCTIVITY, AND MORPHOLOGY OF ECKLONIA RADIATA
      (ALARIACEAE; LAMINARIALES) ALONG A FJORD IN SOUTHERN NEW ZEALAND1.
AB  - Spatial and temporal patterns of growth, erosion, productivity, and morphology of
      the dominant habitat-forming kelp Ecklonia radiata (C. Agardh) J. Agardh were
      studied bimonthly over 1.5 years in a southern New Zealand fjord characterized by
      strong gradients in light and wave exposure. Spatial differences in growth were
      observed with rates at two outer coast, high-light, wave-exposed sites reaching
      0.42 and 0.45 cm . d-1 , respectively, compared to 0.27 cm . d-1 at an inner,
      more homogeneous site. Sporophyte productivity was similar among sites, although
      population productivity was greater at the outer sites due to population density
      being 5-fold greater than at the inner site. It was expected that the inner site
      would have no pronounced seasonal pattern in growth and productivity due to its
      homogeneity; however, all three sites displayed maximum rates in late
      winter/spring and minimal in autumn. Growth rates were 2-fold greater during the
      first growth period than the following year. This discrepancy was not correlated
      to inorganic nitrogen (N) levels, which remained low year-round (<4 MUM), and is
      likely a result of an interaction between light and temperature, and the
      photosynthetic capability of E. radiata. Variable pigment content indicated
      photoacclimation at the inner site. Morphological differences were observed
      between sites, with E. radiata from the inner site having longer, wider, thinner
      blades and longer stipes. While E. radiata displayed spatial differences in
      growth, erosion, productivity, and morphology, populations displayed no temporal
      differences. These results highlight the need for greater understanding of the
      mechanisms influencing kelp growth and productivity in a unique marine
      environment.

PMID- 27021980
TI  - REGULATION OF BIOSYNTHESIS OF DIMETHYLSULFONIOPROPIONATE AND ITS UPTAKE IN
      STERILE MUTANT OF ULVA PERTUSA (CHLOROPHYTA)1.
AB  - It has been shown that marine algae produce the compatible solute
      dimethylsulfoniopropionate (DMSP) from methionine (Met) via four enzymatic
      reactions in which the third step, synthesis of 4-dimethylsulfonio-2-hydroxy
      butyrate (DMSHB) from 4-methylthio-2-hydroxybutyrate (MTHB), is the committing
      step. However, regulation of the biosynthetic pathways and transport properties
      of DMSP is largely unknown. Here, the effects of sulfur and sodium concentrations
      on the uptake and synthesis of DMSHB and DMSP were examined in a sterile mutant
      of Ulva pertusa Kjellm. Sulfur deficiency increased the activity of the sulfur
      assimilation enzyme O-acetyl serine sulfhydrylase but decreased the MTHB S
      methyltransferase activity, suggesting the preferential utilization of sulfur
      atoms for Met metabolites other than DMSP. Uptake of DMSP and DMSHB was enhanced
      by S deficiency. High salinity enhanced the MTHB S-methyltransferase activity as
      well as the uptake of DMSHB. The MTHB S-methyltransferase activity was inhibited
      by its product DMSP. These data demonstrate the importance of MTHB S
      methyltransferase activity and uptake of DMSHB for the regulation of DMSP.

PMID- 27021981
TI  - THE ACCLIMATIVE CHANGES IN PHOTOCHEMISTRY AFTER COLONY FORMATION OF THE
      CYANOBACTERIA MICROCYSTIS AERUGINOSA1.
AB  - Microcystis aeruginosa (Kutz.) Kutz. commonly occurs as single cells at early
      recruitment but forms large colonies in summer. Colony formation will induce many
      acclimative changes. In this study, we demonstrated the photochemical changes
      before and after colony formation. In the laboratory, light curves showed that
      colonies were more responsive to high light than single cells. The values of the
      maximal slope of electron transport rate (ETR)-light curve (alpha), relative
      maximal electron transport rate (rETRmax ), and onset of light saturation (Ik )
      of colonies were significantly higher than those of single cells (P < 0.05),
      indicating that colonies have higher photosynthetic capability than single cells,
      especially in high light, where values of rETRmax and Ik of colonies were 2.32
      and 2.41 times those of single cells. Moreover, the dark-light experiments showed
      that colonial cells can more effectively resist darkness damage. In addition,
      pigments of colonial cells were higher than those of single cells (P < 0.05). The
      higher pigment contents probably contribute to higher photosynthetic capability.
      In the field, the inhibition rate of Fv /Fm in single cells increased
      significantly faster than that of colonies as light increased (P < 0.05), but
      nonphotochemical quenching (NPQ) value of colonies was higher (32.4%) than that
      of single cells at noon, which indicated colonial cells can more effectively
      resist high-light inhibition than single cells (P < 0.05). Polysaccharides of
      colonies were significantly higher compared to those in unicellular cells (P <
      0.05) based on their contents and ultrastructural characteristics. This finding
      implies that colonies could not effectively decrease photoinhibition by negative
      buoyancy regulation. In fact, NPQ may be an important mechanism for avoiding
      photodamage. All of these phenomena can help explain the ecological success of
      colonial M. aeruginosa in eutrophic water.

PMID- 27021982
TI  - POLYOL PATTERNS IN BIOFILM-FORMING AEROTERRESTRIAL GREEN ALGAE (TREBOUXIOPHYCEAE,
      CHLOROPHYTA)1.
AB  - The distribution of polyols was examined for the first time in 34 green algal
      strains from four different clades belonging to the class Trebouxiophyceae, which
      dominate aeroterrestrial biofilms of many regions. Sorbitol was detected in
      representatives of the Prasiola clade, while ribitol was present in the
      Elliptochloris and Watanabea clades. Apatococcus lobatus (Chodat) J. B. Petersen
      contained erythritol in addition to ribitol. Polyols are considered as effective
      stress metabolites exerting multiple protective functions in metabolism and hence
      mainly occur in organisms colonizing extreme environments. In contrast, members
      of the Chlorella clade, which mainly occur in aquatic habitats, did not contain
      polyols. Thus, the constitutive presence of specific polyols facilitates a
      differentiation between species of the Prasiola clade from the Elliptochloris and
      Watanabea clades, respectively, and further allows differentiation of
      morphologically converging taxa.

PMID- 27021983
TI  - POLYAMINE ACCLIMATION ALLEVIATES HYPERSALINITY-INDUCED OXIDATIVE STRESS IN A
      MARINE GREEN MACROALGA, ULVA FASCIATA, BY MODULATION OF ANTIOXIDATIVE ENZYME GENE
      EXPRESSION1.
AB  - Transcripts and enzyme activities of antioxidative enzymes were increased by
      hypersalinity (900/00) in a marine macroalga, Ulva fasciata Delile (Lu et al.
      2006, Sung et al. 2009). This study examined the effects of polyamines (PAs) on
      the induction of hypersalinity tolerance through the modulation of expression of
      antioxidative defense enzymes. Incubation of U. fasciata grown under 300/00 in
      the presence of putrescine (Put), spermidine (Spd), or spermine (Spm) (1 mM) for
      12 h increased internal PA contents prior to 900/00 treatment. Spd or Spm
      pretreatments reduced H2 O2 accumulation and lipid peroxidation during 900/00
      treatment and improved the recovery growth rate after transfer from 900/00 to
      300/00. Increases in iron superoxide dismutase (FeSOD; EC 1.15.1.1) activity and
      transcript levels observed under 900/00 were further increased by Spd and Spm
      pretreatments, while Put pretreatment had no effect. Increases in MnSOD activity
      and transcript levels observed under 900/00 were enhanced by Spd and Put
      pretreatment. An observed increase in catalase (CAT; EC 1.11.1.6) activity and
      transcript levels under 900/00 was not affected by Spd and Spm pretreatments but
      was inhibited by Put pretreatment. Observed increases in ascorbate peroxidase
      (APX; EC 1.11.1.11) activity and transcript levels under 900/00 were inhibited by
      Put, Spd, and Spm pretreatments. In conclusion, Spd and Spm treatment affords U.
      fasciata protection against hypersalinity through the up-regulation of FeSOD gene
      expression, thereby alleviating oxidative damage.

PMID- 27021984
TI  - SEAWEED EXTRACTS AS A POTENTIAL TOOL FOR THE ATTENUATION OF OXIDATIVE DAMAGE IN
      OBESITY-RELATED PATHOLOGIES1.
AB  - Recent studies suggest that seaweed extracts are a significant source of
      bioactive compounds comparable to the dietary phytochemicals such as onion and
      tea extracts. The exploration of natural antioxidants that attenuate oxidative
      damage is important for developing strategies to treat obesity-related
      pathologies. The objective of this study was to screen the effects of seaweed
      extracts of 49 species on adipocyte differentiation and reactive oxygen species
      (ROS) production during the adipogenesis in 3T3-L1 adipocytes, and to investigate
      their total phenol contents and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      scavenging activities. Our results show that high total phenol contents were
      observed in the extracts of Ecklonia cava (see Table 1 for taxonomic authors)
      (681.1 +/- 16.0 MUg gallic acid equivalents [GAE] . g-1 ), Dictyopteris undulata
      (641.3 +/- 70.7 MUg GAE . g-1 ), and Laurencia intermedia (560.9 +/- 48.1 MUg GAE
      . g-1 ). In addition, DPPH radical scavenging activities were markedly higher in
      Sargassum macrocarpum (60.2%), Polysiphonia morrowii (55.0%), and Ishige okamurae
      (52.9%) than those of other seaweed extracts (P < 0.05). Moreover, treatment with
      several seaweed extracts including D. undulata, Sargassum micracanthum, Chondrus
      ocellatus, Gelidium amansii, Gracilaria verrucosa, and Grateloupia lanceolata
      significantly inhibited adipocyte differentiation and ROS production during
      differentiation of 3T3-L1 preadipocytes. Furthermore, the production of ROS was
      positively correlated with lipid accumulation (R2  = 0.8149). According to these
      preliminary results, some of the seaweed extracts can inhibit ROS generation,
      which may protect against oxidative stress that is linked to obesity. Further
      studies are required to determine the molecular mechanism between the verified
      seaweeds and ROS, and the resulting effects on obesity. [Table: see text].

PMID- 27021985
TI  - POTASSIUM ALLEVIATES THE INHIBITORY ACTION OF AMMONIUM UPON THE PHOTOSYNTHETIC
      RECOVERY OF NOSTOC FLAGELLIFORME (CYANOPHYCEAE) DURING REHYDRATION1.
AB  - Effects of ammonium on the photosynthetic recovery of Nostoc flagelliforme Berk.
      et M. A. Curtis were assayed when being rehydrated in low-K+ or high-K+ medium.
      Its photosynthetic recovery was K+ limited after 3 years of dry storage. The
      potassium absorption of N. flagelliforme reached the maximum after 3 h
      rehydration in low-K+ medium but at 5 min in high-K+ medium. The K+ content of N.
      flagelliforme rehydrated in high-K+ medium was much higher than that in low-K+
      medium. The maximal PSII quantum yield (Fv /Fm ) value of N. flagelliforme
      decreased significantly when samples were rehydrated in low-K+ medium treated
      with 5 mM NH4 Cl. However, the treatment of 20 mM NH4 Cl had little effect on its
      Fv /Fm value in high-K+ medium. The relative Fv /Fm 24 h EC50 (concentration at
      which 50% inhibition occurred) value of NH4+ in high-K+ medium (64.35 mM) was
      much higher than that in low-K+ medium (22.17 mM). This finding indicated that
      high K+ could alleviate the inhibitory action of NH4+ upon the photosynthetic
      recovery of N. flagelliforme during rehydration. In the presence of 10 mM
      tetraethylammonium chloride (TEACl), the relative Fv /Fm 24 h EC50 value of NH4+
      was increased to 46.34 and 70.78 mM, respectively, in low-K+ and high-K+ media.
      This observation suggested that NH4+ entered into N. flagelliforme cells via the
      K+ channel. Furthermore, NH4+ could decrease K+ absorption in high-K+ medium.

PMID- 27021986
TI  - INTRACELLULAR METAL COMPARTMENTALIZATION IN THE GREEN ALGAL MODEL SYSTEM
      MICRASTERIAS DENTICULATA (STREPTOPHYTA) MEASURED BY TRANSMISSION ELECTRON
      MICROSCOPY-COUPLED ELECTRON ENERGY LOSS SPECTROSCOPY1.
AB  - Entry of metals in form of aerosols into areas of high air humidity such as peat
      bogs represents a serious danger for inhabiting organisms such as the unicellular
      desmid Micrasterias denticulata Breb. ex Ralfs (Desmidiaceae, Zynematophyceae,
      Streptophyta). To understand cellular detoxification and tolerance mechanisms,
      detailed intracellular localization of metal pollutants is required. This study
      localizes the metals aluminum (Al), zinc (Zn), copper (Cu), and cadmium (Cd) in
      the green algal model system Micrasterias after experimental exposure to sulfate
      solutions by highly sensitive TEM-coupled electron energy loss spectroscopy
      (EELS). Concentrations of the metals shown to induce inhibiting effects on cell
      development and cytomorphogenesis were chosen for these experiments. Long-term
      exposure to these metal concentrations led to a pronounced impact on cell
      physiology expressed by a general decrease in apparent photosynthesis. After long
      term treatment, Zn, Al, and Cu were detected in the cell walls by EELS. Zn was
      additionally found in vacuoles and mucilage vesicles, and Cu in starch grains and
      also in mucilage vesicles. Elevated amounts of oxygen in areas where Zn, Al, and
      Cu were localized suggest sequestration of these metals as oxides. The study
      demonstrated that Micrasterias can cope differently with metal pollutants. In low
      doses and during a limited time period, the cells were able to compartmentalize
      Cu the best, followed by Zn and Al. Cu and Zn were taken up into intracellular
      compartments, whereas Al was only bound to the cell wall. Cd was not
      compartmentalized at all, which explains its strongest impact on growth, cell
      division rate, and photosynthesis in Micrasterias.

PMID- 27021987
TI  - THE FLAGELLAR PHOTORESPONSE IN VOLVOX SPECIES (VOLVOCACEAE, CHLOROPHYCEAE)1.
AB  - Steering their swimming direction toward the light is crucial for the viability
      of Volvox colonies, the larger members of the volvocine algae. While it is known
      that this phototactic steering is achieved by a difference in behavior of the
      flagella on the illuminated and shaded sides, conflicting reports suggest that
      this asymmetry arises either from a change in beating direction or a change in
      beating frequency. Here, we report direct observations of the flagellar behavior
      of various Volvox species with different phyletic origin in response to light
      intensity changes and thereby resolve this controversy: Volvox barberi W. Shaw
      from the section Volvox sensu Nozaki (2003) changes the direction of the
      flagellar beating plane, while species encompassed in the group Eudorina (Volvox
      carteri F. Stein, Volvox aureus Ehrenb., and Volvox tertius Art. Mey.) decrease
      the flagellar beating frequency, sometimes down to flagellar arrest.

PMID- 27021988
TI  - ISOLATION AND TEMPORAL EXPRESSION ANALYSIS OF FRESHWATER-INDUCED GENES IN ULVA
      LIMNETICA (ULVALES, CHLOROPHYTA)1.
AB  - The macroalga Ulva limnetica K. Ichihara et S. Shimada is the only known Ulva
      species to be distributed exclusively in freshwater and is restricted to
      freshwater bodies in the Ryuku archipelago. Molecular phylogenetic analysis
      suggests that U. limnetica originally evolved from marine forms of Ulva. The
      mechanisms of adaptation to freshwater in Ulva spp. are poorly understood. In
      this study, we isolated genes potentially involved in adaptation or tolerance to
      freshwater conditions in U. limnetica, using suppression subtractive
      hybridization between mRNAs of samples cultured in freshwater and seawater
      conditions. A total of 219 genes, up-regulated by the exposure of the macroalga
      to freshwater, were isolated. Reverse transcription-PCR (RT-PCR) revealed 39
      clones, including malate dehydrogenase, soluble starch synthase, triosephosphate
      isomerase, plastid ribosomal protein, DnaJ-like protein, and chloroplast
      ascorbate peroxidase (APX), which were specifically or preferentially expressed
      in freshwater conditions. These 39 clones were also analyzed for their temporal
      transcriptional response to freshwater conditions. A large majority of these up
      regulated genes showed a transient peak of expression after 1-4 h, followed in
      the next 24 h by a decrease to a stable level (over the 7 d of the experiment).
      After the initial response peak, the level of expression either remained higher
      than in the control (long-term response) or returned to a level similar to
      pretreatment level. A few genes showed a more delayed response (i.e., after
      several days) to freshwater exposure. Finally, we discussed the possible
      contributions of the freshwater-induced genes in the acquisition of freshwater
      adaptation or tolerance of U. limnetica.

PMID- 27021989
TI  - DESICCATION STRESS CAUSES STRUCTURAL AND ULTRASTRUCTURAL ALTERATIONS IN THE
      AEROTERRESTRIAL GREEN ALGA KLEBSORMIDIUM CRENULATUM (KLEBSORMIDIOPHYCEAE,
      STREPTOPHYTA) ISOLATED FROM AN ALPINE SOIL CRUST1.
AB  - Klebsormidium crenulatum (Kutz.) Lokhorst (Klebsormidiophyceae, Streptophyta)
      isolated from an alpine soil in Tyrol, Austria, was experimentally exposed to
      desiccation under various relative air humidities (RH 5, 75, and >95%, ambient
      air 55%-60%). The effects on the structure and ultrastructure of K. crenulatum
      after 1, 4, or 7 d of desiccation at 5, 75, and >95% RH were investigated. The
      cross walls were deformed to an undulated shape, and the cell diameter was
      reduced to ~60% of the control. Regardless of the RH applied, in all cases the
      cytoplasm appeared denser compared to that of liquid-culture-grown cells.
      Electron-dense particles with diameters of 0.4 MUm-0.8 MUm were observed in the
      cytoplasm, likely representing lipid droplets. The chloroplasts of desiccated
      samples contained a large number of plastoglobules. The number and appearance of
      mitochondria were not visibly altered, as also verified by 3,3'
      dihexyloxacarbocyanine iodine (DIOC6 ) staining. The amphiphilic styryl dye FM 1
      43 resulted in staining of the plasma membrane in cells from liquid culture. In 7
      d desiccated samples, a marked fluorescence is seen in ~40%-50% of the cells,
      which were dead. Actin microfilaments (MFs) were drastically disrupted after
      desiccation; only dotlike actin batches remained. These results demonstrate that
      flexibility of the cell walls and maintenance of the key organelles play a key
      role in the tolerance of desiccation stress in K. crenulatum.

PMID- 27021990
TI  - SPOROGENESIS UNDER ULTRAVIOLET RADIATION IN LAMINARIA DIGITATA (PHAEOPHYCEAE)
      REVEALS PROTECTION OF PHOTOSENSITIVE MEIOSPORES WITHIN SORAL TISSUE:
      PHYSIOLOGICAL AND ANATOMICAL EVIDENCE1.
AB  - To study the effect of different radiation conditions on sporogenesis of
      Laminaria digitata (Huds.) J. V. Lamour., excised disks were induced to form
      sporangia under PAR (P), PAR + ultraviolet-A (UVA) (PA), and PAR + UVA +
      ultraviolet-B (UVB) (PAB) conditions in the laboratory. Vitality of meiospores,
      released from sori induced under different radiation conditions in the laboratory
      and from sori of wild sporophytes acclimated to in situ solar radiation in the
      presence and absence of ultraviolet radiation (UVR), was measured in terms of
      their germination capacity. Sorus induction in disks of laboratory-grown
      sporophytes was not hampered under light supplemented with UVR, and sorus area
      was not significantly different among P, PA, and PAB. Vitality and germination
      rate of meiospores released from sori induced under different radiation
      treatments was comparable. Likewise, screening of UVR of the natural solar
      radiation did not promote higher germination rates of meiospores released from
      wild sporophytes. Germination rates were, however, higher in meiospores released
      from laboratory-induced sori compared to sori of wild sporophytes. Higher DNA
      damage (formation of cyclobutane pyrimidine dimers, CPDs) was observed in
      laboratory-grown nonsorus compared to sorus tissue, while CPDs were nondetectable
      in both sorus and nonsorus tissue of wild sporophytes. To explain the apparent
      protection of developing meiospores and the unexpected UV resistance of soral
      tissue, concurrent anatomical investigations of sporogenic tissue were performed.
      We observed the previously unreported existence of two types of sterile
      paraphysis cells. One type of paraphysis cells, the most frequent type, contained
      several red-fluorescing plastids. The other type, less frequently occurring, was
      completely filled with substances emitting blue fluorescence under violet
      excitation, presumably brown algal phenolic compounds (phlorotannins). Cells of
      this type were irregularly scattered within the sorus and did not contain red
      fluorescing plastids. Meiospore-containing sporangia were positioned embedded
      between both types of paraphysis cells. In vegetative tissue, blue
      autofluorescence was observed only in injured parts of the blade. Results of our
      study suggest that the sorus structure with phlorotannins localized in the
      specialized paraphysis cells may be able to screen harmful UVR and protect UV
      sensitive meiospores inside the sporangia.

PMID- 27021991
TI  - PHOTOSYNTHETIC PIGMENT AND GENETIC DIFFERENCES BETWEEN TWO SOUTHERN OCEAN
      MORPHOTYPES OF EMILIANIA HUXLEYI (HAPTOPHYTA)1.
AB  - The widespread coccolithophorid Emiliania huxleyi (Lohmann) W. W. Hay et H.
      Mohler plays a pivotal role in the carbon pump and is known to exhibit
      significant morphological, genetic, and physiological diversity. In this study,
      we compared photosynthetic pigments and morphology of triplicate strains of
      Southern Ocean types A and B/C. The two morphotypes differed in width of
      coccolith distal shield elements (0.11-0.24 MUm, type A; 0.06-0.12 MUm, type B/C)
      and morphology of distal shield central area (grill of curved rods in type A;
      thin plain plate in type B/C) and showed differences in carotenoid composition.
      The mean 19'-hexanoyloxyfucoxanthin (Hex):chl a ratio in type B/C was >1, whereas
      the type A ratio was <1. The Hex:fucoxanthin (fuc) ratio for type B/C was 11
      times greater than that for type A, and the proportion of fuc in type A was 6
      times higher than that in type B/C. The fuc derivative 4-keto-19'
      hexanoyloxyfucoxanthin (4-keto-hex) was present in type A but undetected in B/C.
      DNA sequencing of tufA distinguished morphotypes A, B/C (indistinguishable from
      B), and R, while little variation was observed within morphotypes. Thirty single
      nucleotide polymorphisms were identified in the 710 bp tufA sequence, of which 10
      alleles were unique to B/C and B morphotypes, seven alleles were unique to type
      A, and six alleles were unique to type R. We propose that the morphologically,
      physiologically, and genetically distinct Southern Ocean type B/C sensu Young et
      al. (2003) be classified as E. huxleyi var. aurorae var. nov. S. S. Cook et
      Hallegr.

PMID- 27021992
TI  - MOLECULAR PHYLOGENY OF THE UPRIGHT ERYTHROPELTIDALES (COMPSOPOGONOPHYCEAE,
      RHODOPHYTA): MULTIPLE CRYPTIC LINEAGES OF ERYTHROTRICHIA CARNEA1.
AB  - The phylogeny of morphologically simple algae is problematic due to insufficient
      morphological characters to aid in distinguishing species and relationships. The
      problem is further compounded because multiple evolutionary lineages of
      morphologically similar species occur in most well-sampled biogeographic
      locations; therefore, location cannot be used as a proxy for species. The
      phylogeny of the upright members of the Erythropeltidales is partially clarified
      by combining molecular data, unialgal culture observations, and worldwide
      sampling. Our results show that there are several well-supported lineages within
      the Erythropeltidales with only two morphologically recognizable taxa at present.
      The first is the genus Porphyrostromium, with a well-developed basal crust, which
      includes two Erythrotrichia species (Porphyrostromium ligulatum comb. nov. and
      Porphyrostromium pulvinatum comb. nov.). The second is the branched species
      Erythrotrichia welwitschii (Rupr.) Batters. There are also six strongly supported
      Erythrotrichia carnea-like lineages. While not completely satisfactory, we
      propose that one lineage (lineage 2) with samples close to the type locality be
      designated as E. carnea with a specific isolate as an epitype. The lack of
      morphology to differentiate the other lineages leads to a taxonomy based solely
      on gene sequencing and molecular phylogeny, with rbcL sequences differentiating
      the lineages proposed. We hold off on proposing more species and genera until
      more data and samples can be gathered.

PMID- 27021993
TI  - UPDATING THE GENUS DICTYOSPHAERIUM AND DESCRIPTION OF MUCIDOSPHAERIUM GEN. NOV.
      (TREBOUXIOPHYCEAE) BASED ON MORPHOLOGICAL AND MOLECULAR DATA1.
AB  - Recent molecular analyses of Dictyosphaerium strains revealed a polyphyletic
      origin of this morphotype within the Chlorellaceae. The type species
      Dictyosphaerium ehrenbergianum Nageli formed an independent lineage within the
      Parachlorella clade, assigning the genus to this clade. Our study focused on
      three different Dictyosphaerium species to resolve the phylogenetic position of
      remaining species. We used combined analyses of morphology; molecular data based
      on SSU and internally transcribed spacer region (ITS) rRNA sequences; and the
      comparison of the secondary structure of the SSU, ITS-1, and ITS-2 for species
      and generic delineation. The phylogenetic analyses revealed two lineages without
      generic assignment and two distinct clades of Dictyosphaerium-like strains within
      the Parachlorella clade. One clade comprises the lineages with the epitype strain
      of D. ehrenbergianum Nageli and two additional lineages that are described as new
      species (Dictyosphaerium libertatis sp. nov. and Dictyosphaerium lacustre sp.
      nov.). An emendation of the genus Dictyosphaerium is proposed. The second clade
      comprises the species Dictyosphaerium sphagnale Hindak and Dictyosphaerium
      pulchellum H. C. Wood. On the basis of phylogenetic analyses, complementary base
      changes, and morphology, we describe Mucidosphaerium gen. nov with the four
      species Mucidosphaerium sphagnale comb. nov., Mucidosphaerium pulchellum comb.
      nov., Mucidosphaerium palustre sp. nov., and Mucidosphaerium planctonicum sp.
      nov.

PMID- 27021994
TI  - THE SPECIES EUGLENA DESES (EUGLENACEAE) REVISITED: NEW MORPHOLOGICAL AND
      MOLECULAR DATA1.
AB  - For this study, we have examined the literature and the morphological diversity,
      as well as analyzed the nuclear SSU rDNA sequences of two very common and
      cosmopolitan species formerly known as Euglena deses Ehrenb. and Euglena
      intermedia (G. A. Klebs) F. Schmitz. Our studies have shown that there is
      evidence for distinguishing only one species (E. deses). Here, we define new
      diagnostic features for E. deses, namely, periplast ornamentation (the presence
      of small papillae-discovered for the first time in this species) and the lateral
      location of the anterior canal opening, from which the flagellum emerges. We also
      designate the epitype and emend the diagnosis for E. deses.

PMID- 27021995
TI  - REVISION OF THE MASTOPHOROIDEAE (CORALLINALES, RHODOPHYTA) AND POLYPHYLY IN
      NONGENICULATE SPECIES WIDELY DISTRIBUTED ON PACIFIC CORAL REEFS1.
AB  - The subfamily Mastophoroideae (Corallinaceae, Rhodophyta) is characterized by
      species possessing nongeniculate, uniporate tetrasporangial conceptacles without
      apical plugs, the presence of cell fusions, and the absence of secondary pit
      connections. However, molecular phylogenetic studies not including the type genus
      Mastophora indicated that the Mastophoroideae was polyphyletic. Our molecular
      phylogenetic analysis of the subfamily including the type genus using DNA
      sequences of SSU rDNA and plastid-encoded gene of PSII reaction center protein D1
      (psbA) revealed that Mastophora formed a robust clade only with Metamastophora.
      The other mastophoroid genera were divided into six lineages within the family
      Corallinaceae. Five supported lineages-(i) Pneophyllum; (ii) Hydrolithon
      gardineri (Foslie) Verheij et Prud'homme, Hydrolithon onkodes (Heydr.) Penrose et
      Woelk., and Hydrolithon pachydermum (Foslie) J. C. Bailey, J. E. Gabel et
      Freshwater; (iii) Hydrolithon reinboldii (Weber Bosse et Foslie) Foslie; (iv)
      Spongites; and (v) Neogoniolithon-were clearly distinguished by the combination
      of characters including the presence or absence of palisade cells and trichocytes
      in large, tightly packed horizontal fields and features of tetrasporangial and
      spermatangial conceptacles. Therefore, we amend the Mastophoroideae to be limited
      to Mastophora and Metamastophora with a thin thallus with basal filaments
      comprised of palisade cells, tetrasporangial conceptacles formed by filaments
      peripheral to fertile areas, and spermatangia derived only from the floor of male
      conceptacles. This emendation supports Setchell's (1943) original definition of
      the Mastophoroideae as having thin thalli. We also propose the establishment of
      three new subfamilies, Hydrolithoideae subfam. nov. including Hydrolithon,
      Porolithoideae subfam. nov. including the resurrected genus Porolithon, and
      Neogoniolithoideae subfam. nov. including Neogoniolithon. Taxonomic revisions of
      Pneophyllum and Spongites were not made because we did not examine their type
      species.

PMID- 27021996
TI  - A NEW SPECIES OF VOLVOX SECT. MERRILLOSPHAERA (VOLVOCACEAE, CHLOROPHYCEAE) FROM
      TEXAS1.
AB  - Smith (1944) divided the familiar genus Volvox L. into four sections, placing
      seven species that lacked cytoplasmic bridges between adult cells in the section
      Merrillosphaera. Herein, we describe a new member of the section Merrillosphaera
      originating from Texas (USA): Volvox ovalis Pocock ex Nozaki et A. W. Coleman sp.
      nov. Asexual spheroids of V. ovalis are ovoid or elliptical, with a monolayer of
      1,000-2,000 somatic cells that are not linked by cytoplasmic bridges, an expanded
      anterior region, and 8-12 gonidia in the posterior region. Visibly asymmetric
      cleavage divisions do not occur in V. ovalis embryos as they do Volvox carteri F.
      Stein, Volvox obversus (W. Shaw) Printz, and Volvox africanus G. S. West, so the
      gonidia of the next generation are not yet recognizable in V. ovalis embryos
      prior to inversion. Molecular phylogenetic analyses of the five chloroplast genes
      and the internal transcribed spacer (ITS) regions of nuclear rDNA indicated that
      V. ovalis is closely related to Volvox spermatosphaera Powers (Powers 1908, as
      "spermatosphara") and/or Volvox tertius Art. Mey.; however, V. ovalis can be
      distinguished from V. spermatosphaera by its larger gonidia, and from V. tertius
      by visible differences in gonidial chloroplast morphology.

PMID- 27021997
TI  - PHYLOGENETIC AFFINITIES OF "CHANTRANSIA" STAGES IN MEMBERS OF THE
      BATRACHOSPERMALES AND THOREALES (RHODOPHYTA)1.
AB  - This study evaluated the phylogenetic relationship among samples of "Chantransia"
      stage of the Batrachospermales and Thoreales from several regions of the world
      based on sequences of two genes-the plastid-encoded RUBISCO LSU gene (rbcL) and
      the nuclear SSU ribosomal DNA gene (SSU rDNA). All sequences of "Chantransia
      macrospora" were shown to belong to Batrachospermum macrosporum based on both
      molecular markers, confirming evidence from previous studies. In contrast, nine
      species are now associated with "Chantransia pygmaea," including seven species of
      the Batrachospermales and two of the Thoreales. Therefore, the presence of "C.
      macrospora" in a stream can be considered reliable evidence that it belongs to B.
      macrosporum, whereas the occurrence of "C. pygmaea" does not allow the
      recognition of any particular species, since it is associated with at least nine
      species. Affinities of "Chantransia" stages to particular taxa were congruent for
      70.5% of the samples comparing the rbcL and SSU analyses, which were associated
      with the same or closely related species for both markers. Sequence divergences
      have been reported in the "Chantransia" stage in comparison to the respective
      gametophyte, and this matter deserves further attention.

PMID- 27021998
TI  - IDENTIFICATION OF COENZYME Q10 FROM PORPHYRIDIUM PURPUREUM (RHODOPHYTA) BY MATRIX
      ASSISTED LASER DESORPTION IONIZATION CURVED FIELD REFLECTRON MASS SPECTROMETRY1.
AB  - Antioxidant agents from natural sources are currently the focus of scientific
      interest and are part of several natural product screenings. Coenzymes Q (CoQ,
      ubiquinones) are integral parts of the electron transport chain of the inner
      mitochondrial membrane. As antioxidants they protect phospholipids against
      peroxidation and are also involved in various processes of tissue protection.
      Their natural occurrence was validated for Saccharomyces cerevisiae as CoQ6 , for
      Escherichia coli as CoQ8 , and for humans as CoQ10 . After carrying out a
      preparative reversed-phase (RP)-HPLC separation of extracts isolated from
      unicellular red alga Porphyridium purpureum (Bory) K. M. Drew et R. Ross, it was
      possible to identify a 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone
      (CoQ10 ) within these extracts using a matrix-assisted laser desorption
      ionization (MALDI) curved field reflectron (CFR) mass spectrometer. Detected mass
      fragments showed a high significance and could be structurally interpreted for
      both commercialized standard and CoQ10 isolated from P. purpureum.

PMID- 27021999
TI  - FLOW CYTOMETRIC APPLICABILITY OF FLUORESCENT VITALITY PROBES ON PHYTOPLANKTON1.
AB  - The applicability of six fluorescent probes (four esterase probes: acetoxymethyl
      ester of Calcein [Calcein-AM], 5-chloromethylfluorescein diacetate [CMFDA],
      fluorescein diacetate [FDA], and 2',7'-dichlorofluorescein diacetate [H2 DCFDA];
      and two membrane probes: bis-(1,3-dibutylbarbituric acid) trimethine oxonol
      [DiBAC4 (3)] and SYTOX-Green) as vitality stains was tested on live and killed
      cells of 40 phytoplankton strains in exponential and stationary growth phases,
      belonging to 12 classes and consisting of four cold-water, 26 temperate, and four
      warm-water species. The combined live/dead ratios of all six probes indicated
      significant differences between the 12 plankton classes (P < 0.01) and between
      individual species (P < 0.05). No specific differences were observed among
      strains of one species, among species or strains from different origin, nor
      between cells in exponential and stationary growth phase except for FDA. FDA
      showed a significant (P < 0.05) drop of <20% in fluorescence intensity in
      stationary cells. Of the four esterase probes, the live/dead ratios of FDA and
      CMFDA were not significantly different from each other, and both performed better
      than Calcein-AM and H2 DCFDA (P < 0.001). Of the two membrane probes, DIBAC4 (3)
      stained rhodophytes and euglenophytes much better than SYTOX-Green. The 13 algal
      strains best stainable (high live/dead ratios) among all six probes belonged to
      nine genera from six classes of phytoplankton. In conclusion, FDA, CMFDA, DIBAC4
      (3), and SYTOX-Green represent a wide choice of vitality probes in the study of
      phytoplankton ecology, applicable in many species from different algal classes,
      originating from different regions and at different stages of growth.

PMID- 27022000
TI  - DEVELOPMENT OF A MULTIPLEX PCR ASSAY FOR SIMULTANEOUS DETECTION OF SIX
      ALEXANDRIUM SPECIES (DINOPHYCEAE)1.
AB  - In Japan, the bloom seasons of two toxic species, namely, Alexandrium catenella
      (Whedon et Kof.) Balech and Alexandrium tamiyavanichii Balech, sometimes overlap
      with those of three nontoxic Alexandrium species, namely, Alexandrium affine (H.
      Inouye et Fukuyo) Balech, Alexandrium fraterculus (Balech) Balech, and
      Alexandrium pseudogoniaulax (Biecheler) T. Horig. ex Y. Kita et Fukuyo. In this
      study, a multiplex PCR assay has been developed that enables simultaneous
      detection of six Alexandrium species on the basis of differences in the lengths
      of the PCR products. The accuracy of the multiplex PCR system was assessed using
      101 DNA templates of the six target Alexandrium species and 27 DNA templates of
      11 nontarget species (128 DNA templates in total). All amplicons obtained from
      the 101 DNA templates of the target species were appropriately identified,
      whereas all 27 DNA templates of the nontarget species were not amplified. Species
      specific identification by the multiplex PCR assay was certainly possible from
      single cells of the target species.

PMID- 27022001
TI  - Construction of inorganic-organic 2D/2D WO3/g-C3N4 nanosheet arrays toward
      efficient photoelectrochemical splitting of natural seawater.
AB  - Hydrogen production from seawater and solar energy based on photoelectrochemical
      cells is extremely attractive due to earth-abundance of seawater and solar
      radiation. Herein, we report the successful fabrication of novel inorganic
      organic 2D/2D WO3/g-C3N4 nanosheet arrays (WO3/g-C3N4 NSAs) grown on a FTO
      substrate via a facile hydrothermal growth and deposition-annealing process, and
      their application in natural seawater splitting. The results indicate that the
      WO3/g-C3N4 NSAs exhibit a photocurrent density of 0.73 mA cm(-2) at 1.23 V versus
      RHE under AM 1.5G (100 mW cm(-2)) illumination, which is 2-fold higher than that
      of WO3 NSAs. More importantly, the WO3/g-C3N4 NSA photoanode is quite stable
      during seawater splitting and the photocurrent density does not substantially
      decrease after continuous illumination for 3600 s. The remarkably enhanced
      performance originates primarily from the formation of the WO3/g-C3N4
      heterojunction between WO3 and g-C3N4 nanosheets, which accelerates charge
      transfer and separation, and prolongs the lifetime of electrons as demonstrated
      by EIS and Mott-Schottky analyses. Finally, a possible mechanism for the improved
      performance was proposed and discussed.

PMID- 27022002
TI  - Not your regular high: cardiac dysrhythmias caused by loperamide.
AB  - OBJECTIVE: Loperamide, a non-prescription anti-diarrheal agent, is a peripheral
      mu-opioid receptor agonist that is excluded from the blood-brain barrier by p
      glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central
      nervous system (CNS), leading to abuse. We report cardiac conduction
      abnormalities and dysrhythmias after ingestion of a recreational supra
      therapeutic dose of loperamide confirmed with an elevated blood loperamide
      concentration. CASE DETAILS: A 48-year-old woman with a history of alcohol and
      benzodiazepine abuse presented to the emergency department (ED) with somnolence,
      weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1
      2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood
      pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR),
      20/min; T, 36.9  degrees C; O2 saturation 100% on room air (RA). Glucose was 6.4
      mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT
      582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2
      mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L,
      creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average
      therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but
      responded to fluids. Following treatment for hyperkalemia with calcium, insulin,
      dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate
      of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were
      placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of
      54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The
      ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms,
      and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular
      tachycardia that did not require therapy. Over the next 48 h she improved and was
      transferred to a floor bed. On day four of hospitalization the patient left
      against medical advice. At that time, her ECG showed sinus tachycardia with a
      heart rate 114/min, QRS 82 ms, QT 334 ms. DISCUSSION: Loperamide produces both
      QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide
      concentration of 210 ng/mL is among the highest concentrations reported. Supra
      therapeutic dosing of loperamide is promoted on multiple drug-use websites and
      online forums as a treatment for opioid withdrawal, as well as for euphoric
      effects. With the current epidemic of prescription opioid abuse, toxicity related
      to loperamide, an opioid agonist that is readily available without a prescription
      is occurring more frequently. It is important for clinicians to be aware of the
      potentially life-threatening toxicity related to loperamide abuse in order to
      provide proper diagnosis, management and patient education.

PMID- 27022003
TI  - The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by
      single nucleotide polymorphism array and exon sequencing of 100 candidate genes.
AB  - Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8
      years; range 0-17) de novo acute myeloid leukaemia (AML) patients revealed
      aberrations in 55 (82%) cases. The most common subgroups were KMT2A rearrangement
      (29%), normal karyotype (15%), RUNX1-RUNX1T1 (10%), deletions of 5q, 7q and/or
      17p (9%), myeloid leukaemia associated with Down syndrome (7%), PML-RARA (7%) and
      CBFB-MYH11 (5%). Single nucleotide polymorphism array (SNP-A) analysis and exon
      sequencing of 100 genes, performed in 52 and 40 cases, respectively (39
      overlapping), revealed >=1 aberration in 89%; when adding cytogenetic data, this
      frequency increased to 98%. Uniparental isodisomies (UPIDs) were detected in 13%
      and copy number aberrations (CNAs) in 63% (median 2/case); three UPIDs and 22
      CNAs were recurrent. Twenty-two genes were targeted by focal CNAs, including
      AEBP2 and PHF6 deletions and genes involved in AML-associated gene fusions. Deep
      sequencing identified mutations in 65% of cases (median 1/case). In total, 60
      mutations were found in 30 genes, primarily those encoding signalling proteins
      (47%), transcription factors (25%), or epigenetic modifiers (13%). Twelve genes
      (BCOR, CEBPA, FLT3, GATA1, KIT, KRAS, NOTCH1, NPM1, NRAS, PTPN11, SMC3 and TP53)
      were recurrently mutated. We conclude that SNP-A and deep sequencing analyses
      complement the cytogenetic diagnosis of paediatric AML.

PMID- 27022005
TI  - Self-imagination can enhance memory in individuals with schizophrenia.
AB  - OBJECTIVE: Previous research has demonstrated that self-referential strategies
      can be applied to improve memory in various memory- impaired populations.
      However, little is known regarding the relative effectiveness of self-referential
      strategies in schizophrenia patients. The main aim of this study was to assess
      the effectiveness of a new self-referential strategy known as self- imagination
      (SI) on a free recall task. METHODS: Twenty schizophrenia patients and 20 healthy
      controls intentionally encoded words under five instructions: superficial
      processing, semantic processing, semantic self-referential processing, episodic
      self-referential processing and semantic self- imagining. Other measures included
      depression, psychotic symptoms and cognitive measures. RESULTS: We found a SI
      effect in memory as self- imagining resulted in better performance in memory
      retrieval than semantic and superficial encoding in schizophrenia patients. The
      memory boost for self-referenced information in comparison to semantic processing
      was not found for other self-referential strategies. In addition no relationship
      between clinical variables and free recall performances was found. In controls,
      the SI condition did not result in better performance. The three self-referential
      strategies yielded better free recall than both superficial and semantic
      encoding. CONCLUSIONS: This study provides evidence of the clinical utility of
      self-imagining as a mnemonic strategy in schizophrenia patients.

PMID- 27022004
TI  - Distribution of Axial Length before Cataract Surgery in Chinese Pediatric
      Patients.
AB  - Axial length (AL) is a significant indicator of eyeball development, but reports
      on the overall status of axial development in congenital cataract (CC) patients
      and its relationship with patient demographics, such as age, sex, and laterality,
      are rare. We prospectively investigated the AL of 1,586 patients <= 18 years old
      and undergoing cataract surgery in China from January 2005 to December 2014. Of
      these 3,172 eyes, a logarithmic correlation between AL and age in CC patients was
      calculated, and an age of approximately 2 years was found to be a turning point
      in the growth rate of AL. A considerable variation was observed in CC patients of
      the same age. Furthermore, 2-6 years old boys had longer AL than girls. The AL of
      affected eye in unilateral patients was longer than that of the contralateral eye
      in 2-6 years age group and longer than that of eye in bilateral CC patients in
      all age groups. These findings indicate that the development of the length of
      eyeballs in CC patients is influenced by multiple factors in addition to age. A
      full understanding of the distribution of AL may provide a useful reference for
      judging the timing of surgery in CC patients.

PMID- 27022007
TI  - Distribution drivers and physiological responses in geothermal bryophyte
      communities.
AB  - PREMISE OF STUDY: Our ability to explain community structure rests on our ability
      to define the importance of ecological niches, including realized ecological
      niches, in shaping communities, but few studies of plant distributions have
      combined predictive models with physiological measures. METHODS: Using field
      surveys and statistical modeling, we predicted distribution drivers in geothermal
      bryophyte (moss) communities of Lassen Volcanic National Park (California, USA).
      In the laboratory, we used drying and rewetting experiments to test whether the
      strong species-specific effects of relative humidity on distributions predicted
      by the models were correlated with physiological characters. KEY RESULTS: We
      found that the three most common bryophytes in geothermal communities were
      significantly affected by three distinct distribution drivers: temperature,
      light, and relative humidity. Aulacomnium palustre, whose distribution is
      significantly affected by relative humidity according to our model, and which
      occurs in high-humidity sites, showed extreme signs of stress after drying and
      never recovered optimal values of PSII efficiency after rewetting. Campylopus
      introflexus, whose distribution is not affected by humidity according to our
      model, was able to maintain optimal values of PSII efficiency for 48 hr at 50%
      water loss and recovered optimal values of PSII efficiency after rewetting.
      CONCLUSIONS: Our results suggest that species-specific environmental stressors
      tightly constrain the ecological niches of geothermal bryophytes. Tests of
      tolerance to drying in two bryophyte species corresponded with model predictions
      of the comparative importance of relative humidity as distribution drivers for
      these species.

PMID- 27022008
TI  - Adapting to a warming world: Ecological restoration, climate change, and
      genomics.

PMID- 27022009
TI  - Editorial Comment for McVey et al.

PMID- 27022010
TI  - Cryo-EM Visualization of Nanobubbles in Aqueous Solutions.
AB  - The detection of nanobubbles on surfaces is well established (e.g., AFM and
      optical microscopy methods), but currently no methods exist for the direct
      detection of bulk nanobubbles. Here, cryo-electron microscopy (cryo-EM) has been
      employed to observe bubbles in aqueous solutions for the first time. Nitrogen
      bubbles generated by a chemical reaction were observed in amorphous ice trapped
      between two carbon films. The cryo-EM images of bubbles showed the same features
      as predicted by theory. The fact that no bubbles were observed near an air-water
      interface suggests that bubbles may diffuse to the nearby air-water interface and
      escape. The estimate of the bubble diffusion coefficient is about 30-250 MUm2/s.

PMID- 27022011
TI  - A new non-tumescent endovenous ablation method for varicose vein treatment: Early
      results of N-butyl cyanoacrylate (VariClose(r)).
AB  - Objective This report aims to present the early results of a retrospective study
      of the use of N-butyl cyanoacrylate (VariClose(r))-based non-tumescent endovenous
      ablation for the treatment of patients with varicose veins. Method One hundred
      and eighty patients with varicose veins due to incompetent saphenous veins were
      treated with the VariClose(r) endovenous ablation method between May 2014 and
      November 2014. The patient sample consisted of 86 men and 94 women, with a mean
      age of 47.7 +/- 11.7 years. The patients had a great saphenous vein diameter
      greater than 5.5 mm and a small saphenous vein diameter greater than 4 mm in
      conjunction with reflux for more than 0.5 s. Patients with varicose veins were
      evaluated with venous duplex examination, Clinical, Etiological, Anatomical and
      Pathophysiological classification (CEAP), and their Venous Clinical Severity
      Scores were recorded. Results The median CEAP score of patients was three, and
      the saphenous vein diameters were between 5.5 and 14 mm (mean of 7.7 +/- 2.1 mm).
      A percutaneous entry was made under local anesthesia to the great saphenous vein
      in 169 patients and to the small saphenous vein in 11 patients. Duplex
      examination immediately after the procedure showed closure of the treated vein in
      100% of the treated segment. No complications were observed. The mean follow-up
      time was 5.5 months (ranging from three to seven months). Recanalization was not
      observed in any of the patients during follow-up. The average Venous Clinical
      Severity Scores was 10.2 before the procedure and decreased to 3.9 after three
      months (p < 0.001). Conclusion The application of N-butyl cyanoacrylate
      (VariClose(r)) is an effective method for treating varicose veins; it yielded a
      high endovenous closure rate, with no need for tumescent anesthesia. However,
      long-term results are currently unknown.

PMID- 27022012
TI  - Mid-term outcome of endovascular treatment for acute lower extremity deep venous
      thrombosis.
AB  - Purposes of the study To evaluate the benefit of stenting the iliac vein in
      patients with residual iliac vein stenosis treated with catheter-directed
      thrombolysis for acute iliofemoral deep venous thrombosis. Procedures In this
      randomized prospective study, patients with a first-time acute lower extremity
      deep venous thrombosis that had persisted <14 days were treated with catheter
      directed thrombolysis. After catheter-directed thrombolysis, patients with >50%
      residual iliac vein stenosis were randomly divided into two groups: catheter
      directed thrombolysis + Stent Group and catheter-directed thrombolysis Alone
      Group. Patients received urokinase thrombolysis and low-molecular-weight
      heparin/oral warfarin during the hospitalization period and were administrated
      oral warfarin after discharge. Cumulative deep vein patency, the Clinical
      Etiology Anatomic Pathophysiologic classification system, the Venous Clinical
      Severity Score and the Chronic Venous Insufficiency Questionnaire score were
      evaluated. Findings The cumulative deep vein patency rate was 74.07% in the
      catheter-directed thrombolysis + Stent Group and 46.59% in the catheter-directed
      thrombolysis Alone Group. The mean postoperative Clinical Etiology Anatomic
      Pathophysiologic classification and Venous Clinical Severity Score was
      significantly lower in the catheter-directed thrombolysis + Stent Group than in
      the catheter-directed thrombolysis Alone Group. The mean postoperative Chronic
      Venous Insufficiency Questionnaire score was significantly higher in the catheter
      directed thrombolysis + Stent Group than the catheter-directed thrombolysis Alone
      Group. Conclusions Placement of an iliac vein stent in patients with residual
      iliac vein stenosis after catheter-directed thrombolysis for acute lower
      extremity deep venous thrombosis increases iliac vein patency and improves
      clinical symptoms and health-related quality of life at mid-term follow-up
      compared to patients treated with catheter-directed thrombolysis alone.

PMID- 27022014
TI  - Correction. Heritability and genome-wide association analyses of intracranial
      carotid artery calcification: The Rotterdam Study.

PMID- 27022015
TI  - Testing for negligible interaction: A coherent and robust approach.
AB  - Researchers often want to demonstrate a lack of interaction between two
      categorical predictors on an outcome. To justify a lack of interaction,
      researchers typically accept the null hypothesis of no interaction from a
      conventional analysis of variance (ANOVA). This method is inappropriate as
      failure to reject the null hypothesis does not provide statistical evidence to
      support a lack of interaction. This study proposes a bootstrap-based intersection
      union test for negligible interaction that provides coherent decisions between
      the omnibus test and post hoc interaction contrast tests and is robust to
      violations of the normality and variance homogeneity assumptions. Further, a
      multiple comparison strategy for testing interaction contrasts following a non
      significant omnibus test is proposed. Our simulation study compared the Type I
      error control, omnibus power and per-contrast power of the proposed approach to
      the non-centrality-based negligible interaction test of Cheng and Shao (2007,
      Statistica Sinica, 17, 1441). For 2 * 2 designs, the empirical Type I error rates
      of the Cheng and Shao test were very close to the nominal alpha level when the
      normality and variance homogeneity assumptions were satisfied; however, only our
      proposed bootstrapping approach was satisfactory under non-normality and/or
      variance heterogeneity. In general a * b designs, although the omnibus Cheng and
      Shao test, as expected, is the most powerful, it is not robust to assumption
      violation and results in incoherent omnibus and interaction contrast decisions
      that are not possible with the intersection-union approach. 

PMID- 27022016
TI  - How You Use It Matters: Object Function Guides Attention During Visual Search in
      Scenes.
AB  - How does one know where to look for objects in scenes? Objects are seen in
      context daily, but also used for specific purposes. Here, we examined whether an
      object's function can guide attention during visual search in scenes. In
      Experiment 1, participants studied either the function (function group) or
      features (feature group) of a set of invented objects. In a subsequent search,
      the function group located studied objects faster than novel (unstudied) objects,
      whereas the feature group did not. In Experiment 2, invented objects were
      positioned in locations that were either congruent or incongruent with the
      objects' functions. Search for studied objects was faster for function-congruent
      locations and hampered for function-incongruent locations, relative to search for
      novel objects. These findings demonstrate that knowledge of object function can
      guide attention in scenes, and they have important implications for theories of
      visual cognition, cognitive neuroscience, and developmental and ecological
      psychology.

PMID- 27022017
TI  - Do Src Kinase and Caveolin Interact Directly with Na,K-ATPase?
AB  - Much evidence points to a role of Na,K-ATPase in ouabain-dependent signal
      transduction. Based on experiments with different cell lines and native tissue
      membranes, a current hypothesis postulates direct interactions between the Na,K
      ATPase and Src kinase (non-receptor tyrosine kinase). Na,K-ATPase is proposed to
      bind Src kinase and inhibit its activity, whereas ouabain, the specific Na,K
      ATPase inhibitor, binds and stabilizes the E2 conformation, thus exposing the Src
      kinase domain and its active site Tyr-418 for activation. Ouabain-dependent
      signaling is thought to be mediated within caveolae by a complex consisting of
      Na,K-ATPase, caveolin, and Src kinase. In the current work, we have looked for
      direct interactions utilizing purified recombinant Na,K-ATPase (human
      alpha1beta1FXYD1 or porcine alpha1D369Nbeta1FXYD1) and purified human Src kinase
      and human caveolin 1 or interactions between these proteins in native membrane
      vesicles isolated from rabbit kidney. By several independent criteria and
      techniques, no stable interactions were detected between Na,K-ATPase and purified
      Src kinase. Na,K-ATPase was found to be a substrate for Src kinase
      phosphorylation at Tyr-144. Clear evidence for a direct interaction between
      purified human Na,K-ATPase and human caveolin was obtained, albeit with a low
      molar stoichiometry (1:15-30 caveolin 1/Na,K-ATPase). In native renal membranes,
      a specific caveolin 14-5 oligomer (95 kDa) was found to be in direct interaction
      with Na,K-ATPase. We inferred that a small fraction of the renal Na,K-ATPase
      molecules is in a ~1:1 complex with a caveolin 14-5 oligomer. Thus, overall,
      whereas a direct caveolin 1/Na,K-ATPase interaction is confirmed, the lack of
      direct Src kinase/Na,K-ATPase binding requires reassessment of the mechanism of
      ouabain-dependent signaling.

PMID- 27022019
TI  - Helicase Activity Plays a Crucial Role for RNase R Function in Vivo and for RNA
      Metabolism.
AB  - RNase R is a 3' to 5' hydrolytic exoribonuclease that has the unusual ability to
      digest highly structured RNA. The enzyme possesses an intrinsic, ATP-dependent
      RNA helicase activity that is essential in vitro for efficient nuclease activity
      against double-stranded RNA substrates, particularly at lower temperatures, with
      more stable RNA duplexes, and for duplexes with short 3' overhangs. Here, we
      inquired whether the helicase activity was also important for RNase R function in
      vivo and for RNA metabolism. We find that strains containing a helicase-deficient
      RNase R due to mutations in its ATP-binding Walker motifs exhibit growth defects
      at low temperatures. Most importantly, cells also lacking polynucleotide
      phosphorylase (PNPase), and dependent for growth on RNase R, grow extremely
      poorly at 34, 37, and 42  degrees C and do not grow at all at 31  degrees C.
      Northern analysis revealed that in these cells, fragments of 16S and 23S rRNA
      accumulate to high levels, leading to interference with ribosome maturation and
      ultimately to cell death. These findings indicate that the intrinsic helicase
      activity of RNase R is required for its proper functioning in vivo and for
      effective RNA metabolism. 

PMID- 27022018
TI  - Regulation of Receptor for Advanced Glycation End Products (RAGE) Ectodomain
      Shedding and Its Role in Cell Function.
AB  - The receptor for advanced glycation end products (RAGE) is a multiligand
      transmembrane receptor that can undergo proteolysis at the cell surface to
      release a soluble ectodomain. Here we observed that ectodomain shedding of RAGE
      is critical for its role in regulating signaling and cellular function.
      Ectodomain shedding of both human and mouse RAGE was dependent on ADAM10 activity
      and induced with chemical activators of shedding (ionomycin, phorbol 12-myristate
      13-acetate, and 4-aminophenylmercuric acetate) and endogenous stimuli (serum and
      RAGE ligands). Ectopic expression of the splice variant of RAGE (RAGE splice
      variant 4), which is resistant to ectodomain shedding, inhibited RAGE ligand
      dependent cell signaling, actin cytoskeleton reorganization, cell spreading, and
      cell migration. We found that blockade of RAGE ligand signaling with soluble RAGE
      or inhibitors of MAPK or PI3K blocked RAGE-dependent cell migration but did not
      affect RAGE splice variant 4 cell migration. We finally demonstrated that RAGE
      function is dependent on secretase activity as ADAM10 and gamma-secretase
      inhibitors blocked RAGE ligand-mediated cell migration. Together, our data
      suggest that proteolysis of RAGE is critical to mediate signaling and cell
      function and may therefore emerge as a novel therapeutic target for RAGE
      dependent disease states.

PMID- 27022020
TI  - Benzothiazole Amphiphiles Promote the Formation of Dendritic Spines in Primary
      Hippocampal Neurons.
AB  - The majority of excitatory synapses in the brain exist on dendritic spines.
      Accordingly, the regulation of dendritic spine density in the hippocampus is
      thought to play a central role in learning and memory. The development of novel
      methods to control spine density could, therefore, have important implications
      for treatment of a host of neurodegenerative and developmental cognitive
      disorders. Herein, we report the design and evaluation of a new class of
      benzothiazole amphiphiles that exhibit a dose-dependent response leading to an
      increase in dendritic spine density in primary hippocampal neurons. Cell exposure
      studies reveal that the increase in spine density can persist for days in the
      presence of these compounds, but returns to normal spine density levels within 24
      h when the compounds are removed, demonstrating the capability to reversibly
      control spinogenic activity. Time-lapse imaging of dissociated hippocampal
      neuronal cultures shows that these compounds promote a net increase in spine
      density through the formation of new spines. Biochemical studies support that
      promotion of spine formation by these compounds is accompanied by Ras activation.
      These spinogenic molecules were also capable of inhibiting a suspected mechanism
      for dendritic spine loss induced by Alzheimer-related aggregated amyloid-beta
      peptides in primary neurons. Evaluation of this new group of spinogenic agents
      reveals that they also exhibit relatively low toxicity at concentrations
      displaying activity. Collectively, these results suggest that small molecules
      that promote spine formation could be potentially useful for ameliorating
      cognitive deficiencies associated with spine loss in neurodegenerative diseases
      such as Alzheimer disease, and may also find use as general cognitive enhancers.

PMID- 27022021
TI  - Evolution of Heat Sensors Drove Shifts in Thermosensation between Xenopus Species
      Adapted to Different Thermal Niches.
AB  - Temperature is one of the most critical environmental factors affecting survival,
      and thus species that inhabit different thermal niches have evolved thermal
      sensitivities suitable for their respective habitats. During the process of
      shifting thermal niches, various types of genes expressed in diverse tissues,
      including those of the peripheral to central nervous systems, are potentially
      involved in the evolutionary changes in thermosensation. To elucidate the
      molecular mechanisms behind the evolution of thermosensation, thermal responses
      were compared between two species of clawed frogs (Xenopus laevis and Xenopus
      tropicalis) adapted to different thermal environments. X. laevis was much more
      sensitive to heat stimulation than X. tropicalis at the behavioral and neural
      levels. The activity and sensitivity of the heat-sensing TRPA1 channel were
      higher in X. laevis compared with those of X. tropicalis The thermal responses of
      another heat-sensing channel, TRPV1, also differed between the two Xenopus
      species. The species differences in Xenopus TRPV1 heat responses were largely
      determined by three amino acid substitutions located in the first three ankyrin
      repeat domains, known to be involved in the regulation of rat TRPV1 activity. In
      addition, Xenopus TRPV1 exhibited drastic species differences in sensitivity to
      capsaicin, contained in chili peppers, between the two Xenopus species. Another
      single amino acid substitution within Xenopus TRPV1 is responsible for this
      species difference, which likely alters the neural and behavioral responses to
      capsaicin. These combined subtle amino acid substitutions in peripheral thermal
      sensors potentially serve as a driving force for the evolution of thermal and
      chemical sensation. 

PMID- 27022022
TI  - A Modeling and Experimental Investigation of the Effects of Antigen Density,
      Binding Affinity, and Antigen Expression Ratio on Bispecific Antibody Binding to
      Cell Surface Targets.
AB  - Despite the increasing number of multivalent antibodies, bispecific antibodies,
      fusion proteins, and targeted nanoparticles that have been generated and studied,
      the mechanism of multivalent binding to cell surface targets is not well
      understood. Here, we describe a conceptual and mathematical model of multivalent
      antibody binding to cell surface antigens. Our model predicts that properties
      beyond 1:1 antibody:antigen affinity to target antigens have a strong influence
      on multivalent binding. Predicted crucial properties include the structure and
      flexibility of the antibody construct, the target antigen(s) and binding
      epitope(s), and the density of antigens on the cell surface. For bispecific
      antibodies, the ratio of the expression levels of the two target antigens is
      predicted to be critical to target binding, particularly for the lower expressed
      of the antigens. Using bispecific antibodies of different valencies to cell
      surface antigens including MET and EGF receptor, we have experimentally validated
      our modeling approach and its predictions and observed several nonintuitive
      effects of avidity related to antigen density, target ratio, and antibody
      affinity. In some biological circumstances, the effect we have predicted and
      measured varied from the monovalent binding interaction by several orders of
      magnitude. Moreover, our mathematical framework affords us a mechanistic
      interpretation of our observations and suggests strategies to achieve the desired
      antibody-antigen binding goals. These mechanistic insights have implications in
      antibody engineering and structure/activity relationship determination in a
      variety of biological contexts. 

PMID- 27022023
TI  - The Methionine Transamination Pathway Controls Hepatic Glucose Metabolism through
      Regulation of the GCN5 Acetyltransferase and the PGC-1alpha Transcriptional
      Coactivator.
AB  - Methionine is an essential sulfur amino acid that is engaged in key cellular
      functions such as protein synthesis and is a precursor for critical metabolites
      involved in maintaining cellular homeostasis. In mammals, in response to nutrient
      conditions, the liver plays a significant role in regulating methionine
      concentrations by altering its flux through the transmethylation,
      transsulfuration, and transamination metabolic pathways. A comprehensive
      understanding of how hepatic methionine metabolism intersects with other
      regulatory nutrient signaling and transcriptional events is, however, lacking.
      Here, we show that methionine and derived-sulfur metabolites in the
      transamination pathway activate the GCN5 acetyltransferase promoting acetylation
      of the transcriptional coactivator PGC-1alpha to control hepatic gluconeogenesis.
      Methionine was the only essential amino acid that rapidly induced PGC-1alpha
      acetylation through activating the GCN5 acetyltransferase. Experiments employing
      metabolic pathway intermediates revealed that methionine transamination, and not
      the transmethylation or transsulfuration pathways, contributed to methionine
      induced PGC-1alpha acetylation. Moreover, aminooxyacetic acid, a transaminase
      inhibitor, was able to potently suppress PGC-1alpha acetylation stimulated by
      methionine, which was accompanied by predicted alterations in PGC-1alpha-mediated
      gluconeogenic gene expression and glucose production in primary murine
      hepatocytes. Methionine administration in mice likewise induced hepatic PGC
      1alpha acetylation, suppressed the gluconeogenic gene program, and lowered
      glycemia, indicating that a similar phenomenon occurs in vivo These results
      highlight a communication between methionine metabolism and PGC-1alpha-mediated
      hepatic gluconeogenesis, suggesting that influencing methionine metabolic flux
      has the potential to be therapeutically exploited for diabetes treatment. 

PMID- 27022024
TI  - Modeling the Etiology of p53-mutated Cancer Cells.
AB  - p53 gene mutations are among the most common alterations in cancer. In most
      cases, missense mutations in one TP53 allele are followed by loss-of
      heterozygosity (LOH), so tumors express only mutant p53. TP53 mutations and LOH
      have been linked, in many cases, with poor therapy response and worse outcome.
      Despite this, remarkably little is known about how TP53 point mutations are
      acquired, how LOH occurs, or the cells involved. Nutlin-3a occupies the p53
      binding site in MDM2 and blocks p53-MDM2 interaction, resulting in the
      stabilization and activation of p53 and subsequent growth arrest or apoptosis. We
      leveraged the powerful growth inhibitory activity of Nutlin-3a to select p53
      mutated cells and examined how TP53 mutations arise and how the remaining wild
      type allele is lost or inactivated. Mismatch repair (MMR)-deficient colorectal
      cancer cells formed heterozygote (p53 wild-type/mutant) colonies when cultured in
      low doses of Nutlin-3a, whereas MMR-corrected counterparts did not. Placing these
      heterozygotes in higher Nutlin-3a doses selected clones in which the remaining
      wild-type TP53 was silenced. Our data suggest silencing occurred through a novel
      mechanism that does not involve DNA methylation, histone methylation, or histone
      deacetylation. These data indicate MMR deficiency in colorectal cancer can give
      rise to initiating TP53 mutations and that TP53 silencing occurs via a copy
      neutral mechanism. Moreover, the data highlight the use of MDM2 antagonists as
      tools to study mechanisms of TP53 mutation acquisition and wild-type allele loss
      or silencing in cells with defined genetic backgrounds. 

PMID- 27022025
TI  - Structural Basis for the Failure of the C1 Domain of Ras Guanine Nucleotide
      Releasing Protein 2 (RasGRP2) to Bind Phorbol Ester with High Affinity.
AB  - The C1 domain represents the recognition module for diacylglycerol and phorbol
      esters in protein kinase C, Ras guanine nucleotide releasing protein (RasGRP),
      and related proteins. RasGRP2 is exceptional in that its C1 domain has very weak
      binding affinity (Kd = 2890 +/- 240 nm for [(3)H]phorbol 12,13-dibutyrate. We
      have identified four amino acid residues responsible for this lack of
      sensitivity. Replacing Asn(7), Ser(8), Ala(19), and Ile(21) with the
      corresponding residues from RasGRP1/3 (Thr(7), Tyr(8), Gly(19), and Leu(21),
      respectively) conferred potent binding affinity (Kd = 1.47 +/- 0.03 nm) in vitro
      and membrane translocation in response to phorbol 12-myristate 13-acetate in
      LNCaP cells. Mutant C1 domains incorporating one to three of the four residues
      showed intermediate behavior with S8Y making the greatest contribution. Binding
      activity for diacylglycerol was restored in parallel. The requirement for anionic
      phospholipid for [(3)H]phorbol 12,13-dibutyrate binding was determined; it
      decreased in going from the single S8Y mutant to the quadruple mutant. The full
      length RasGRP2 protein with the mutated C1 domains also showed strong phorbol
      ester binding, albeit modestly weaker than that of the C1 domain alone (Kd = 8.2
      +/- 1.1 nm for the full-length protein containing all four mutations), and
      displayed translocation in response to phorbol ester. RasGRP2 is a guanyl
      exchange factor for Rap1. Consistent with the ability of phorbol ester to induce
      translocation of the full-length RasGRP2 with the mutated C1 domain, phorbol
      ester enhanced the ability of the mutated RasGRP2 to activate Rap1. Modeling
      confirmed that the four mutations helped the binding cleft maintain a stable
      conformation. 

PMID- 27022026
TI  - Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus
      lactis.
AB  - To ensure optimal cell growth and separation and to adapt to environmental
      parameters, bacteria have to maintain a balance between cell wall (CW) rigidity
      and flexibility. This can be achieved by a concerted action of peptidoglycan (PG)
      hydrolases and PG-synthesizing/modifying enzymes. In a search for new regulatory
      mechanisms responsible for the maintenance of this equilibrium in Lactococcus
      lactis, we isolated mutants that are resistant to the PG hydrolase lysozyme. We
      found that 14% of the causative mutations were mapped in the guaA gene, the
      product of which is involved in purine metabolism. Genetic and transcriptional
      analyses combined with PG structure determination of the guaA mutant enabled us
      to reveal the pivotal role of the pyrB gene in the regulation of CW rigidity. Our
      results indicate that conversion of l-aspartate (l-Asp) to N-carbamoyl-l
      aspartate by PyrB may reduce the amount of l-Asp available for PG synthesis and
      thus cause the appearance of Asp/Asn-less stem peptides in PG. Such stem peptides
      do not form PG cross-bridges, resulting in a decrease in PG cross-linking and,
      consequently, reduced PG thickness and rigidity. We hypothesize that the
      concurrent utilization of l-Asp for pyrimidine and PG synthesis may be part of
      the regulatory scheme, ensuring CW flexibility during exponential growth and
      rigidity in stationary phase. The fact that l-Asp availability is dependent on
      nucleotide metabolism, which is tightly regulated in accordance with the growth
      rate, provides L. lactis cells the means to ensure optimal CW plasticity without
      the need to control the expression of PG synthesis genes. 

PMID- 27022027
TI  - PilN Binding Modulates the Structure and Binding Partners of the Pseudomonas
      aeruginosa Type IVa Pilus Protein PilM.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type
      IVa pili. The pilus assembly system, which promotes surface-associated twitching
      motility and virulence, is composed of inner and outer membrane subcomplexes,
      connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N
      terminus of PilN, and we hypothesize that this interaction causes functionally
      significant structural changes in PilM. To characterize this interaction, we
      determined the crystal structures of PilM and a PilM chimera where PilM was fused
      to the first 12 residues of PilN (PilM.PilN(1-12)). Structural analysis,
      multiangle light scattering coupled with size exclusion chromatography, and
      bacterial two-hybrid data revealed that PilM forms dimers mediated by the binding
      of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates
      this binding interface, resulting in PilM monomerization. Structural comparison
      of PilM with PilM.PilN(1-12) revealed that upon PilN binding, there is a large
      domain closure in PilM that alters its ATP binding site. Using biolayer
      interferometry, we found that the association rate of PilN with PilM is higher in
      the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the
      connectivity of the cytoplasmic and inner membrane components of the type IVa
      pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in
      addition to PilN. Pull-down experiments demonstrated direct interactions of PilM
      with PilB and PilT. We propose a working model in which dynamic binding of PilN
      facilitates functionally relevant structural changes in PilM. 

PMID- 27022028
TI  - Structure-Function Relationships in l-Amino Acid Deaminase, a Flavoprotein
      Belonging to a Novel Class of Biotechnologically Relevant Enzymes.
AB  - l-Amino acid deaminase from Proteus myxofaciens (PmaLAAD) is a membrane
      flavoenzyme that catalyzes the deamination of neutral and aromatic l-amino acids
      into alpha-keto acids and ammonia. PmaLAAD does not use dioxygen to re-oxidize
      reduced FADH2 and thus does not produce hydrogen peroxide; instead, it uses a
      cytochrome b-like protein as an electron acceptor. Although the overall fold of
      this enzyme resembles that of known amine or amino acid oxidases, it shows the
      following specific structural features: an additional novel alpha+beta subdomain
      placed close to the putative transmembrane alpha-helix and to the active-site
      entrance; an FAD isoalloxazine ring exposed to solvent; and a large and
      accessible active site suitable to bind large hydrophobic substrates. In
      addition, PmaLAAD requires substrate-induced conformational changes of part of
      the active site, particularly in Arg-316 and Phe-318, to achieve the correct
      geometry for catalysis. These studies are expected to pave the way for rationally
      improving the versatility of this flavoenzyme, which is critical for biocatalysis
      of enantiomerically pure amino acids. 

PMID- 27022029
TI  - Fine-tuning of Substrate Affinity Leads to Alternative Roles of Mycobacterium
      tuberculosis Fe2+-ATPases.
AB  - Little is known about iron efflux transporters within bacterial systems.
      Recently, the participation of Bacillus subtilis PfeT, a P1B4-ATPase, in
      cytoplasmic Fe(2+) efflux has been proposed. We report here the distinct roles of
      mycobacterial P1B4-ATPases in the homeostasis of Co(2+) and Fe(2+) Mutation of
      Mycobacterium smegmatis ctpJ affects the homeostasis of both ions. Alternatively,
      an M. tuberculosis ctpJ mutant is more sensitive to Co(2+) than Fe(2+), whereas
      mutation of the homologous M. tuberculosis ctpD leads to Fe(2+) sensitivity but
      no alterations in Co(2+) homeostasis. In vitro, the three enzymes are activated
      by both Fe(2+) and Co(2+) and bind 1 eq of either ion at their transport site.
      However, equilibrium binding affinities and activity kinetics show that M.
      tuberculosis CtpD has higher affinity for Fe(2+) and twice the Fe(2+)-stimulated
      activity than the CtpJs. These parameters are paralleled by a lower activation
      and affinity for Co(2+) Analysis of Fe(2+) and Co(2+) binding to CtpD by x-ray
      absorption spectroscopy shows that both ions are five- to six-coordinate,
      constrained within oxygen/nitrogen environments with similar geometries.
      Mutagenesis studies suggest the involvement of invariant Ser, His, and Glu
      residues in metal coordination. Interestingly, replacement of the conserved Cys
      at the metal binding pocket leads to a large reduction in Fe(2+) but not Co(2+)
      binding affinity. We propose that CtpJ ATPases participate in the control of
      steady state Fe(2+) levels. CtpD, required for M. tuberculosis virulence, is a
      high affinity Fe(2+) transporter involved in the rapid response to iron
      dyshomeostasis generated upon redox stress.

PMID- 27022030
TI  - Toll/Interleukin-1 Receptor Domain Derived from TcpC (TIR-TcpC) Ameliorates
      Experimental Autoimmune Arthritis by Down-modulating Th17 Cell Response.
AB  - Evasion through immunomodulation is one of the several strategies adopted by
      pathogens to prolong their survival within the host. One such pathogen,
      Escherichia coli CFT073, utilizes an immunomodulatory protein, TcpC, to combat
      the host's innate immune defense. TcpC abrogates the function of MyD88 in
      macrophages, thus perturbing all the signaling processes that involve this
      adaptor protein. Although central to various signaling pathways initiated by IL
      1, IL-18, and toll-like receptors, the precise contribution of MyD88 to the
      development of autoimmunity, particularly rheumatoid arthritis, still needs
      extensive exploration. Herein, by using the toll/interleukin-1 receptor (TIR)
      domain homologous C-terminal motif of TcpC, i.e. TIR-TcpC, we found MyD88 to be
      critical for the induction and progression of rheumatoid arthritis through its
      pivotal role in the development of Th17 cells, the subset of CD4(+) T-cells
      widely implicated in various autoimmune disorders. The TIR-TcpC mediated
      inhibition of signaling through MyD88, and subsequent amelioration of
      experimental autoimmune arthritis was observed to be an outcome of perturbations
      in the NFkappaB-RORgammat (RAR-related orphan receptor gammat) axis.

PMID- 27022031
TI  - Toll-like Receptor 4 on Macrophage Promotes the Development of Steatohepatitis
      related Hepatocellular Carcinoma in Mice.
AB  - The role of Toll-like receptor (TLR) signaling has attracted much attention in
      the development of hepatic inflammation and hepatocellular carcinoma (HCC). We
      herein sought to determine the role of TLRs and responsible cells in
      steatohepatitis-related HCC. We used hepatocyte-specific Pten-deficient
      (Pten(Delta) (hep)) mice, which exhibit steatohepatitis followed by liver tumor
      formation, including HCC. We then generated Pten(Delta) (hep)/Tlr4(-/-) and
      Pten(Delta) (hep)/Tlr2(-/-) double-mutant mice and investigated the role of
      macrophages using reconstitution of bone marrow (BM)-derived cells, chemical
      depletion of macrophages, and isolated macrophages. Tlr4 but not Tlr2 deficiency
      in the Pten(Delta) (hep) mice suppressed tumor growth as well as hepatic
      inflammation. Gut sterilization by an antibiotic mixture reduced the portal LPS
      levels as well as tumor growth in the Pten(Delta) (hep) mice. Tumor growth was
      also decreased by reconstitution of BM-derived cells to Tlr4(-/-) BM cells. In
      addition, chemical depletion of macrophages significantly reduced tumor size and
      numbers. Macrophages expressing Ly6C were increased in number, which was
      associated with inflammation and tumor progression in the Pten(Delta) (hep) mice.
      Hepatic macrophages isolated from the Pten(Delta) (hep) mice abundantly expressed
      the Ly6C gene and produced much more IL-6 and TNFalpha in response to LPS. These
      proinflammatory cytokines induced the proliferation of HCC cells as well as oval
      cells, putative cancer progenitor cells. Indeed, putative cancer progenitor cells
      emerged before the development of macroscopic liver tumors and then increased in
      number under sustained inflammation. TLR4 on macrophages contributes to the
      development of steatohepatitis-related HCC in mice.

PMID- 27022032
TI  - Dietary Protein Intake and Risk of Type 2 Diabetes in US Men and Women.
AB  - Dietary proteins are important modulators of glucose metabolism. However, few
      longitudinal studies have evaluated the associations between intake of protein
      and protein type and risk of type 2 diabetes (T2D). We investigated the
      associations between total, animal, and vegetable protein and incident T2D in
      72,992 women from the Nurses' Health Study (1984-2008), 92,088 women from Nurses'
      Health Study II (1991-2009) and 40,722 men from the Health Professionals Follow
      up Study (1986-2008). During 4,146,216 person-years of follow-up, we documented
      15,580 cases of T2D. In pooled multivariate models including body mass index,
      participants in the highest quintiles of percentage of energy derived from total
      protein and animal protein had 7% (95% confidence interval (CI): 1, 17) and 13%
      (95% CI: 6, 21) increased risks of T2D compared with those in the lowest
      quintiles, respectively. Percentage of energy intake from vegetable protein was
      associated with a moderately decreased risk of T2D (comparing extreme quintiles,
      hazard ratio =0.91, 95% CI: 0.84, 0.98). Substituting 5% of energy intake from
      vegetable protein for animal protein was associated with a 23% (95% CI: 16, 30)
      reduced risk of T2D. In conclusion, higher intake of animal protein was
      associated with an increased risk of T2D, while higher intake of vegetable
      protein was associated with a modestly reduced risk.

PMID- 27022033
TI  - Physical Activity Types and Coronary Heart Disease Risk in Middle-Aged and
      Elderly Persons: The Rotterdam Study.
AB  - Physical activity is associated with decreased risk of coronary heart disease
      (CHD). The specific physical activity types that provide beneficial effects in an
      older population remain unclear. We assessed the association of total physical
      activity, walking, cycling, domestic work, sports, and gardening with CHD by
      using Cox proportional hazard models among 5,901 participants aged >55 (median
      age, 67) years from the prospective population-based Rotterdam Study, enrolled
      between 1997 and 2001. Activities were categorized into tertiles, and the lowest
      tertiles were used as reference. In the multivariable model, we adjusted for age,
      sex, smoking, alcohol consumption, education, diet, and other physical activity
      types. During 15 years of follow-up (median, 10.3 (interquartile range, 8.0-11.8)
      years), 642 participants (10.9%) experienced a CHD event. In the multivariable
      model, the respective hazard ratios for the medium and high categories compared
      with the low category were 0.79 (95% confidence interval CI): 0.66, 0.96) and
      0.71 (95% CI: 0.58, 0.87) for total physical activity, 0.76 (95% CI: 0.63, 0.92)
      and 0.70 (95% CI: 0.57, 0.88) for cycling, and 0.81 (95% CI: 0.66, 0.98) and 0.71
      (95% CI: 0.56, 0.90) for domestic work. Walking, sports, and gardening were not
      associated with CHD. In conclusion, in this long-term follow-up study of older
      adults, domestic work and cycling were associated with reduced CHD risk. Physical
      activity should be promoted in this population with the aim to prevent CHD.

PMID- 27022034
TI  - Facilitators and Barriers of Community-Level Quality Improvement for Maternal and
      Newborn Health in Tanzania.
AB  - A quality improvement intervention for maternal and newborn health was carried
      out in southern Tanzania at the community level. It sought to improve health
      seeking behaviors and uptake of community-level maternal and newborn health
      practices. A process evaluation populated using data primarily from in-depth
      interviews and focus group discussions with the intervention's implementers was
      undertaken in four villages receiving the intervention to evaluate the
      intervention's implementation, uncover facilitators and barriers of quality
      improvement, and highlight contextual factors that might have influenced
      implementation. Performance implementation scores were used to rank the villages.
      Identifying higher- and lower-performing villages highlighted key facilitators
      and barriers of community-level quality improvement related to support from local
      leaders, motivation through use of local quality improvement data, and regular
      education around quality improvement and maternal and newborn health. These
      findings can be taken formatively in the design of similar interventions in the
      future.

PMID- 27022035
TI  - How many biological replicates are needed in an RNA-seq experiment and which
      differential expression tool should you use?
AB  - RNA-seq is now the technology of choice for genome-wide differential gene
      expression experiments, but it is not clear how many biological replicates are
      needed to ensure valid biological interpretation of the results or which
      statistical tools are best for analyzing the data. An RNA-seq experiment with 48
      biological replicates in each of two conditions was performed to answer these
      questions and provide guidelines for experimental design. With three biological
      replicates, nine of the 11 tools evaluated found only 20%-40% of the
      significantly differentially expressed (SDE) genes identified with the full set
      of 42 clean replicates. This rises to >85% for the subset of SDE genes changing
      in expression by more than fourfold. To achieve >85% for all SDE genes regardless
      of fold change requires more than 20 biological replicates. The same nine tools
      successfully control their false discovery rate at ?5% for all numbers of
      replicates, while the remaining two tools fail to control their FDR adequately,
      particularly for low numbers of replicates. For future RNA-seq experiments, these
      results suggest that at least six biological replicates should be used, rising to
      at least 12 when it is important to identify SDE genes for all fold changes. If
      fewer than 12 replicates are used, a superior combination of true positive and
      false positive performances makes edgeR and DESeq2 the leading tools. For higher
      replicate numbers, minimizing false positives is more important and DESeq
      marginally outperforms the other tools.

PMID- 27022036
TI  - MET Exon 14 Skipping in Non-Small Cell Lung Cancer.
AB  - BACKGROUND: Non-small cell lung cancers (NSCLCs) harboring specific genetic
      alterations can be highly sensitive to targeted therapies. MATERIALS AND METHODS:
      We performed a targeted rearrangement assay on 54 NSCLCs across all stages that
      were from patients who were never smokers and did not have driver mutations.
      Because MET exon 14 skipping was the most frequent alteration found, we surveyed
      the results for MET exon 14 skipping at Massachusetts General Hospital (MGH)
      since the inclusion of this alteration into our current molecular profiling
      panel. RESULTS: In a cohort of 54 never-smokers with lung cancers that were wild
      type for known driver mutations, MET exon 14 skipping was the most frequently
      recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via
      our next-generation sequencing (NGS) and NGS-rearrangement panels showed an
      additional 16 cases of MET exon 14 skipping, for an overall estimated frequency
      of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the
      MET inhibitor crizotinib is also described. CONCLUSION: MET exon 14 skipping is a
      targetable gene alteration found in NSCLC. Patients with these alterations may
      respond well to MET inhibition. IMPLICATIONS FOR PRACTICE: MET exon 14 skipping
      occurs with an approximately 5% frequency in NSCLC and is seen in both squamous
      and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping
      can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping
      should be performed on all lung cancers because this is a targetable alteration.

PMID- 27022037
TI  - Clinical Application of Poly(ADP-Ribose) Polymerase Inhibitors in High-Grade
      Serous Ovarian Cancer.
AB  - : High-grade serous ovarian cancer is characterized by genomic instability, with
      one half of all tumors displaying defects in the important DNA repair pathway of
      homologous recombination. Given the action of poly(ADP-ribose) polymerase (PARP)
      inhibitors in targeting tumors with deficiencies in this repair pathway by loss
      of BRCA1/2, ovarian tumors could be an attractive population for clinical
      application of this therapy. PARP inhibitors have moved into clinical practice in
      the past few years, with approval from the Food and Drug Administration (FDA) and
      European Medicines Agency (EMA) within the past 2 years. The U.S. FDA approval of
      olaparib applies to fourth line treatment in germline BRCA-mutant ovarian cancer,
      and European EMA approval to olaparib maintenance in both germline and somatic
      BRCA-mutant platinum-sensitive ovarian cancer. In order to widen the ovarian
      cancer patient population that would benefit from PARP inhibitors, predictive
      biomarkers based on a clear understanding of the mechanism of action are
      required. Additionally, a better understanding of the toxicity profile is needed
      if PARP inhibitors are to be used in the curative, rather than the palliative,
      setting. We reviewed the development of PARP inhibitors in phase I-III clinical
      trials, including combination trials of PARP inhibitors and
      chemotherapy/antiangiogenics, the approval for these agents, the mechanisms of
      resistance, and the outstanding issues, including the development of biomarkers
      and the rate of long-term hematologic toxicities with these agents. IMPLICATIONS
      FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has
      recently received approval from the Food and Drug Administration (FDA) and
      European Medicines Agency (EMA), with a second agent (rucaparib) likely to be
      approved in the near future. However, the patient population with potential
      benefit from PARP inhibitors is likely wider than that of germline BRCA mutation
      associated disease, and biomarkers are in development to enable the selection of
      patients with the potential for clinical benefit from these agents. Questions
      remain regarding the toxicities of PARP inhibitors, limiting the use of these
      agents in the prophylactic or adjuvant setting until more information is
      available. The indications for olaparib as indicated by the FDA and EMA are
      reviewed.

PMID- 27022038
TI  - Novel Treatments for Rare Cancers: The U.S. Orphan Drug Act Is Delivering-A Cross
      Sectional Analysis.
AB  - BACKGROUND: Rare cancers are a heterogeneous group of conditions with highly
      unmet medical needs. Although infrequent in individuals, rare cancers affect
      millions of people who deserve effective treatments. Therefore, we systematically
      analyzed the impact of the U.S. Orphan Drug Act of 1983 on delivery of novel
      treatments for rare cancers. METHODS: Quantitative cross-sectional analysis was
      conducted on the U.S. Food and Drug Administration Orphan Drug Product database
      according to Strengthening the Reporting of Observational Studies in Epidemiology
      Statement criteria between 1983 and 2015. RESULTS: Since 1983, a total of 177
      approvals have originated from 1,391 orphan drug designations to treat rare
      cancers, which represents 36% of all approvals within the U.S. orphan drug act (n
      = 492). Two compounds (1%) to treat rare cancer were withdrawn after approval.
      Median time from designation to approval was 2.49 years (interquartile range 1.13
      4.64) and decreased significantly over time (p < .001, linear regression). Over
      the last decade, rare cancer treatments have been transformed from nonspecific
      cytotoxic agents toward targeted therapies, such as protein kinase inhibitors and
      monoclonal antibodies, representing the largest groups of innovative rare cancer
      treatments today. Most compounds were approved to treat solid tumors and
      hematological malignancies. CONCLUSION: The U.S. Orphan Drug Act and associated
      incentives, such as 7 years of marketing exclusivity, have fostered delivery of
      novel treatments for rare cancers. More than one-third of all orphan drug
      approvals address needs of patients suffering from rare cancers. Over the last
      decade, the understanding of tumorigenesis and genetic driver mutations in
      different tumor entities has produced innovative treatments, of which many were
      first approved within the U.S. Orphan Drug Act. IMPLICATIONS FOR PRACTICE: Over
      the last 30 years, the U.S. Orphan Drug Act successfully delivered numerous novel
      treatments for rare cancers, of which some were subsequently used in other,
      nonorphan indications. The understanding of molecular mechanisms of diseases is
      directly connected to the search for novel therapies. The constant pursuit to
      translate basic research findings into clinical practice is a crucial
      prerequisite to address unmet medical needs in rare cancers, as in other rare
      diseases. Oncological drug development proves to be a major player in overall
      orphan drug research, displayed by more than one-third of all U.S. Food and Drug
      Administration-approved orphan drugs with oncological indications.

PMID- 27022040
TI  - How to Manage Occult Atrial Fibrillation Detected on Long-Term Monitoring.

PMID- 27022042
TI  - Hypertrophic Cardiomyopathy Attributable to Mitochondrial DNA Mutation Diagnosed
      by Pathology and Gene Sequencing.

PMID- 27022043
TI  - Notes From the Incoming Editor: Second Installment.

PMID- 27022044
TI  - Aorta-Right Atrial Tunnel: Is Surgical Correction Mandatory?

PMID- 27022039
TI  - Vascular Toxicities of Cancer Therapies: The Old and the New--An Evolving Avenue.
AB  - Since the late 1990s, there has been a steady decline in cancer-related
      mortality, in part related to the introduction of so-called targeted therapies.
      Intended to interfere with a specific molecular pathway, these therapies have,
      paradoxically, led to a number of effects off their intended cancer tissue or
      molecular targets. The latest examples are tyrosine kinase inhibitors targeting
      the Philadelphia Chromosome mutation product, which have been associated with
      progressive atherosclerosis and acute vascular events. In addition, agents
      designed to interfere with the vascular growth factor signaling pathway have
      vascular side effects ranging from hypertension to arterial events and
      cardiomyocyte toxicity. Interestingly, the risk of cardiotoxicity with drugs such
      as trastuzumab is predicted by preexisting cardiovascular risk factors and
      disease, posing the question of a vascular component to the pathophysiology. The
      effect on the coronary circulation has been the leading explanation for the
      cardiotoxicity of 5-fluorouracil and may be the underlying the mechanism of
      presentation of apical ballooning syndrome with various chemotherapeutic agents.
      Classical chemotherapeutic agents such as cisplatin, often used in combination
      with bleomycin and vinca alkaloids, can lead to vascular events including acute
      coronary thrombosis and may be associated with an increased long-term
      cardiovascular risk. This review is intended to provide an update on the evolving
      spectrum of vascular toxicities with cancer therapeutics, particularly as they
      pertain to clinical practice, and to the conceptualization of cardiovascular
      diseases, as well. Vascular toxicity with cancer therapy: the old and the new, an
      evolving avenue. 

PMID- 27022045
TI  - Letter by Sheppard et al Regarding Article, "Arrhythmic Mitral Valve Prolapse and
      Sudden Cardiac Death".

PMID- 27022046
TI  - Letter by Providencia and Lambiase Regarding Article, "Arrhythmic Mitral Valve
      Prolapse and Sudden Cardiac Death".

PMID- 27022048
TI  - Letter by Robinson Regarding Articles, "Bringing Back Targets to 'IMPROVE'
      Atherosclerotic Cardiovascular Disease Outcomes: The Duel for Dual Goals; Are Two
      Targets Better Than One?" and "Achievement of Dual Low-Density Lipoprotein
      Cholesterol and High-Sensitivity C-Reactive Protein Targets More Frequent With
      the Addition of Ezetimibe to Simvastatin and Associated With Better Outcomes in
      IMPROVE-IT".

PMID- 27022047
TI  - Response to Letters Regarding Article, "Arrhythmic Mitral Valve Prolapse and
      Sudden Cardiac Death".

PMID- 27022049
TI  - Response to the Letter Regarding Article, "Bringing Back Targets to 'IMPROVE'
      Atherosclerotic Cardiovascular Disease Outcomes: The Duel for Dual Goals; Are Two
      Targets Better Than One?".

PMID- 27022050
TI  - Response to Letter Regarding Article, "Achievement of Dual Low-Density
      Lipoprotein Cholesterol and High-Sensitivity C-Reactive Protein Targets More
      Frequent With the Addition of Ezetimibe to Simvastatin and Associated With Better
      Outcomes in IMPROVE-IT".

PMID- 27022053
TI  - Correction.

PMID- 27022052
TI  - Correction.

PMID- 27022055
TI  - Correction.

PMID- 27022054
TI  - Correction.

PMID- 27022057
TI  - Correction.

PMID- 27022056
TI  - Correction.

PMID- 27022059
TI  - Combustible cigarettes cost less to use than e-cigarettes: global evidence and
      tax policy implications.
AB  - BACKGROUND: Some scholars suggest that price differences between combustible
      cigarettes and e-cigarettes could be effective in moving current combustible
      smokers to e-cigarettes, which could reduce tobacco-related death and disease.
      Currently, in most jurisdictions, e-cigarettes are not subject to the same excise
      taxes as combustible cigarettes, potentially providing the category with a price
      advantage over combustible cigarettes. This paper tests whether e-cigarettes tax
      advantage has translated into a price advantage. METHODS: In a sample of 45
      countries, the price of combustible cigarettes, disposable e-cigarettes and
      rechargeable cigarettes were compared. RESULTS: Comparable units of combustible
      cigarettes cost less than disposable e-cigarettes in almost every country in the
      sample. While the e-liquids consumed in rechargeable e-cigarettes might cost less
      per comparable unit than combustible cigarettes, the initial cost to purchase a
      rechargeable e-cigarette presents a significant cost barrier to switching from
      smoking to vaping. DISCUSSION: Existing prices of e-cigarettes are generally much
      higher than of combustible cigarettes. If policymakers wish to tax e-cigarettes
      less than combustibles, forceful policy action-almost certainly through excise
      taxation-must raise the price of combustible cigarettes beyond the price of using
      e-cigarettes.

PMID- 27022058
TI  - A Practical Concussion Physical Examination Toolbox.
AB  - CONTEXT: With heightened awareness of concussion, there is a need to assess and
      manage the concussed patient in a consistent manner. Unfortunately, concussion
      physical examination has not been standardized or supported by evidence.
      Important questions remain about the physical examination. EVIDENCE ACQUISITION:
      Review of ClinicalKey, Cochrane, MEDLINE, and PubMed prior to July 2015 was
      performed using search terms, including concussion, mTBI, physical examination,
      mental status, cranial nerves, reflexes, cervical, vestibular, and oculomotor.
      The references of the pertinent articles were reviewed for other relevant
      sources. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: The
      pertinent physical examination elements for concussion include evaluation of
      cranial nerves, manual muscle testing, and deep tendon reflexes; inspecting the
      head and neck for trauma or tenderness and cervical range of motion; Spurling
      maneuver; a static or dynamic balance assessment; screening ocular examination;
      and a mental status examination that includes orientation, immediate and delayed
      recall, concentration, mood, affect, insight, and judgment. Other examination
      elements to consider, based on signs, symptoms, or clinical suspicion, include
      testing of upper motor neurons, cervical strength and proprioception,
      coordination, pupillary reactivity, and visual acuity; examination of the jaw,
      temporomandibular joint, and thoracic spine; fundoscopic evaluation; orthostatic
      vital signs; assessment of dynamic visual acuity; and screening for depression,
      anxiety, substance abuse disorders, and preinjury psychiatric difficulties.
      CONCLUSION: Various elements of the physical examination, such as screening
      ocular examination, cervical musculoskeletal examination, static and/or dynamic
      balance assessment, and mental status examination, appear to have utility for
      evaluating concussion; however, data on validity are lacking.

PMID- 27022060
TI  - Serial Changes of the Cartilage in Recipient Sites and Their Mirror Sites on
      Second-Look Imaging After Mosaicplasty.
AB  - BACKGROUND: It has been reported that the short-term results of mosaicplasty are
      good, but there have been no reports of the serial cartilage changes in the
      recipient sites and their mirror sites for mosaicplasty. PURPOSE: To examine the
      serial changes in cartilage in the recipient sites and their mirror sites using
      second-look imaging. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A
      total of 33 patients (37 knees, 40 sites) underwent mosaicplasty and second-look
      arthroscopy at a single institution over a 7-year period. There were 14 men and
      19 women (12 right knees and 25 left knees). The recipient sites were the patella
      (n = 3), trochlea (n = 7), medial femoral condyle (n = 21), and lateral femoral
      condyle (n = 9). The mean patient age at surgery was 38.3 years; the mean period
      from mosaicplasty to second-look arthroscopy was 15.4 months; and the mean follow
      up period was 34.9 months (range, 24-65 months). The results of second-look
      arthroscopy at the recipient site were categorized as cartilage with a smooth
      surface (group S) and fibrillation or an irregular surface (group I), and results
      of second-look arthroscopy at the mirror site were categorized as worse (group
      W), improved (group E), and unchanged (group U). RESULTS: There were 30 sites in
      group S, 10 sites in group I, 3 sites in group W, 4 sites in group E, and 33
      sites in group U. The age at operation was significantly greater in group S than
      in group I. There was a significant correlation between group S and groups E and
      U. The clinical outcome was significantly worse in group W when compared with
      groups E and U. CONCLUSION: If a smooth surface was seen in the recipient site
      during second-look arthroscopy, the cartilage degeneration in its mirror site did
      not become worse after mosaicplasty.

PMID- 27022061
TI  - Precollegiate Knee Surgery Predicts Subsequent Injury Requiring Surgery in NCAA
      Athletes.
AB  - BACKGROUND: The effect of precollegiate orthopaedic surgery on injury risk in the
      elite collegiate athlete is unknown. PURPOSE: To (1) assess the relationship
      between precollegiate surgery and subsequent injury requiring surgery in National
      Collegiate Athletic Association (NCAA) Division I athletes at a single
      institution and (2) compare the risk of subsequent surgery in the ipsilateral
      versus contralateral extremity in those with a history of precollegiate surgery.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective chart
      review was performed of all athletes who began participation from 2003 to 2009
      until completion of eligibility. Athletes who received orthopaedic surgery in
      college were identified through the Sports Injury Monitoring System and were
      cross-referenced with medical records. The risk of orthopaedic surgery was
      evaluated using multivariate Cox and Poisson regression models, with sex and
      sport as additional covariates. Risk of subsequent surgery in the ipsilateral
      versus contralateral extremity was compared using Kaplan-Meier survival estimates
      and Cox proportional hazards regression. Hazard ratios (HRs) and rate ratios
      (RRs) with corresponding 95% confidence intervals were used to compare groups.
      RESULTS: In total, 1141 athletes were identified for analysis. Of these, 186
      athletes (16.3%) had a history of precollegiate orthopaedic surgery. There were
      261 documented intracollegiate orthopaedic surgeries in 181 athletes (15.9%).
      Precollegiate knee surgery was an independent predictor of orthopaedic surgery
      (HR, 1.85; 95% CI, 1.16-2.83) in college. When examining only surgeries resulting
      from acute or primary injuries, precollegiate knee surgery was an independent
      predictor of primary knee injury requiring surgery in college (HR, 4.45; 95% CI,
      2.51-7.59). Athletes with a history of precollegiate surgery were more
      susceptible to subsequent surgery in their ipsilateral extremity compared with
      their other extremities (HR, 1.89; 95% CI, 1.03-3.53). In contrast, there was no
      additional risk of receiving subsequent surgery in the contralateral extremity (P
      = .54). CONCLUSION: Precollegiate knee surgery in the Division I athlete is
      associated with subsequent injury requiring surgery in college. Athletes with a
      history of precollegiate surgery are at higher risk of subsequent surgery in
      their ipsilateral extremity compared with other extremities.

PMID- 27022062
TI  - Concussion Incidence and Return-to-Play Time in National Basketball Association
      Players: Results From 2006 to 2014.
AB  - BACKGROUND: Various research efforts have studied concussions in the National
      Football League, Major League Baseball, and the National Hockey League. However,
      no study has investigated the incidence and return-to-play trends in the National
      Basketball Association (NBA), which this study aims to do. HYPOTHESIS: Increased
      media scrutiny and public awareness, in addition to the institution of a league
      wide concussion protocol, may have resulted in more conservative return-to-play
      practices. STUDY DESIGN: Descriptive epidemiology study. METHODS: All concussions
      to NBA players that were publicly reported in the media from the beginning of the
      2006 NBA season to the end of the 2014 season were included. The incidence and
      return-to-play statistics were generated by synthesizing information from
      publicly available records. RESULTS: There were 134 publicly reported concussions
      to NBA players from the beginning of the 2006 season to the conclusion of the
      2014 season, resulting in an average of 14.9 concussions per season. The
      incidence has not changed significantly during this time span. The average games
      missed after a concussion from 2006 to 2010 was 1.6, significantly less than the
      5.0 games missed from 2011 to 2014, following the institution of the NBA
      concussion protocol (P = .023). CONCLUSION: Although the incidence of publicly
      reported concussions in the NBA has not changed appreciably over the past 9
      seasons, the time missed after a concussion has. While players often returned in
      the same game in the 2006 season, the combination of implemented policy, national
      coverage, medical staff awareness, and player education may have contributed to
      players now missing an average of 4 to 6 games after a concussion. A multitude of
      factors has resulted in more conservative return-to-play practices for NBA
      players after concussions.

PMID- 27022063
TI  - Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac
      Death: A Science Advisory From the American Heart Association.

PMID- 27022064
TI  - Menthol and Nonmenthol Cigarette Smoking: All-Cause Deaths, Cardiovascular
      Disease Deaths, and Other Causes of Death Among Blacks and Whites.
AB  - BACKGROUND: In contrast to whites, black smokers prefer menthol cigarettes over
      nonmenthol cigarettes by a large margin and tend to have higher mortality from
      several smoking-related diseases than whites, raising the possibility that
      menthol cigarettes contribute to racial disparities in risk. Evidence for
      differential associations between menthol and nonmenthol cigarettes indicates
      lower cancer risk for menthol smokers, but for cardiovascular disease (CVD)
      mortality, evidence has been inconsistent. METHODS AND RESULTS: Cox proportional
      hazards models were used to compute hazard ratios and accompanying 95% confidence
      intervals for all-cause and CVD mortality for menthol compared with nonmenthol
      cigarette smokers among 65 600 participants in the Southern Community Cohort
      Study, an ongoing community-based cohort with the largest number of menthol
      smokers being traced. Among the 27 619 current cigarette smokers, 4224 died
      during follow-up, with 1130 deaths attributed to CVD. Both all-cause (hazard
      ratio=0.93; 95% confidence interval=0.86-1.01; P=0.10) and CVD (hazard
      ratio=0.88; 95% confidence interval=0.76-1.03; P=0.10) mortality risks were
      similar in menthol compared with nonmenthol cigarette smokers. CONCLUSIONS:
      Smoking regardless of cigarette type is hazardous to health, but these results do
      not indicate that menthol cigarettes are associated with greater CVD risks than
      nonmenthol cigarettes.

PMID- 27022065
TI  - Trop-2 Induces Tumor Growth Through AKT and Determines Sensitivity to AKT
      Inhibitors.
AB  - PURPOSE: Inhibition of AKT is a key target area for personalized cancer medicine.
      However, predictive markers of response to AKT inhibitors are lacking.
      Correspondingly, the AKT-dependent chain of command for tumor growth, which will
      mediate AKT-dependent therapeutic responses, remains unclear. EXPERIMENTAL
      DESIGN: Proteomic profiling was utilized to identify nodal hubs of the Trop-2
      cancer growth-driving network. Kinase-specific inhibitors were used to dissect
      Trop-2-dependent from Trop-2-independent pathways. In vitro assays, in vivo
      preclinical models, and case series of primary human breast cancers were utilized
      to define the mechanisms of Trop-2-driven growth and the mode of action of Trop-2
      predicted AKT inhibitors. RESULTS: Trop-2 and AKT expression was shown to be
      tightly coordinated in human breast cancers, with virtual overlap with AKT
      activation profiles at T308 and S473, consistent with functional interaction in
      vivo AKT allosteric inhibitors were shown to only block the growth of Trop-2
      expressing tumor cells, both in vitro and in preclinical models, being
      ineffective on Trop-2-null cells. Consistently, AKT-targeted siRNA only impacted
      on Trop-2-expressing cells. Lentiviral downregulation of endogenous Trop-2
      abolished tumor response to AKT blockade, indicating Trop-2 as a mandatory
      activator of AKT. CONCLUSIONS: Our findings indicate that the expression of Trop
      2 is a stringent predictor of tumor response to AKT inhibitors. They also support
      the identification of target-activatory pathways, as efficient predictors of
      response in precision cancer therapy. Clin Cancer Res; 22(16); 4197-205. (c)2016
      AACR.

PMID- 27022066
TI  - Response to angiotensin blockade with irbesartan in a patient with metastatic
      colorectal cancer.
AB  - BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment
      related toxicity and resistance to standard chemotherapy and radiation was
      assessed as part of a personalized oncogenomics initiative to derive potential
      alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and
      transcriptome sequencing was used to interrogate a metastatic tumor refractory to
      standard treatments of a patient with mismatch repair-deficient metastatic
      colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression
      of the AP-1 transcriptional complex suggesting experimental therapeutic
      rationales, including blockade of the renin-angiotensin system. This led to the
      repurposing of the angiotensin II receptor antagonist, irbesartan, as an
      anticancer therapy, resulting in the patient experiencing a dramatic and durable
      response. CONCLUSIONS: This case highlights the utility of comprehensive
      integrative genomic profiling and bioinformatics analysis to provide hypothetical
      rationales for personalized treatment options.

PMID- 27022067
TI  - A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor
      targeting heat shock protein 27 (Hsp27), in patients with castration-resistant
      prostate cancer and other advanced cancers.
AB  - BACKGROUND: Heat shock protein 27 (Hsp27) is a chaperone protein that regulates
      cell survival via androgen receptor and other signaling pathways, thereby
      mediating cancer progression. Apatorsen (OGX-427) is a 2'-methoxyethyl-modified
      antisense oligonucleotide that inhibits Hsp27 expression. This study evaluated
      the safety profile and recommended phase II dosing of apatorsen in patients with
      advanced cancer. PATIENTS AND METHODS: Patients with castration-resistant
      prostate (CRPC), breast, ovary, lung, or bladder cancer were enrolled to this
      phase I dose-escalation study. Apatorsen was administered i.v. weekly in 21-day
      cycles following 3 loading doses and over 5 dose levels (200-1000 mg). Apatorsen
      plasma concentrations, circulating tumor cells (CTCs) and CTC Hsp27 expression,
      and serum Hsp27 levels were evaluated. RESULTS: Forty-two patients were accrued,
      of which 52% had CRPC. Patients were heavily pretreated, with 57% having had >=3
      prior chemotherapy regimens. During the loading dose/cycle 1 and overall study
      period, 93% and 100% of patients (N = 42) experienced treatment-related adverse
      events, respectively; most were grade 1-2 and included chills, pruritus,
      flushing, prolonged aPTT, lymphopenia, and anemia. One patient experienced a dose
      limiting toxicity at the 600 mg dose level (intracranial hemorrhage in a
      previously undiagnosed brain metastasis). A maximum tolerated dose was not
      defined. Apatorsen Cmax increased proportionally with dose. Decreases in tumor
      markers and declines in CTCs were observed, with a prostate-specific antigen
      decline >%50% occurring in 10% of patients with CRPC; 29/39 assessable patients
      (74%) had reductions from >=5 CTC/7.5 ml at baseline to <5 CTC/7.5 ml post
      treatment. Twelve patients had stable measurable disease as best response.
      CONCLUSIONS: Apatorsen was tolerated at the highest dose evaluated (1000 mg).
      Single-agent activity was suggested by changes in tumor markers, CTC, and stable
      measurable disease. Phase II studies evaluating apatorsen are underway.
      CLINICALTRIALSGOV ID: NCT00487786.

PMID- 27022069
TI  - Implementation of Clinical Decision Support Rules to Reduce Repeat Measurement of
      Serum Ionized Calcium, Serum Magnesium, and N-Terminal Pro-B-Type Natriuretic
      Peptide in Intensive Care Unit Inpatients.
AB  - BACKGROUND: We assessed the impact of clinical decision support (CDS) rules
      within the electronic health record for ionized calcium (iCa), serum magnesium
      (Mg), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in intensive care
      unit (ICU) inpatients at a large academic center. METHODS: A repeat order for
      measurement of iCa or Mg placed within 24 (iCa) or 48 (Mg) h of a previously
      nonactionable result, or additional orders for NT-proBNP beyond 1 within a single
      hospitalization, triggered a CDS pop-up alert showing the prior result and
      offering the opportunity to cancel the order or to place the order after entering
      an indication for repeat testing. The number of tests performed for each of these
      analytes and incidence of adverse clinical outcomes potentially associated with
      hypocalcemia or hypomagnesemia were compared between the 90-day period before CDS
      implementation and two 90-day periods immediately following. RESULTS: iCa test
      volumes decreased by 48%, Mg by 39%, and NT-proBNP by 28% in the 90-day period
      immediately following implementation and remained decreased by 54%, 49%, and 22%,
      respectively, during the following 90-day period (all P values <0.0002). Adverse
      clinical outcomes potentially associated with hypocalcemia or hypomagnesemia did
      not increase (all P-values >0.17). CONCLUSIONS: Implementation of CDS
      dramatically decreased repeat testing of iCa, Mg, and NT-proBNP without adversely
      impacting clinical outcomes in the ICU. Expansion of the rules from the ICU units
      to include the entire hospitalized patient population and expansion to additional
      analytes is expected to lead to further reductions in testing.

PMID- 27022068
TI  - Comparison of prognostic and predictive impact of genomic or central grade and
      immunohistochemical subtypes or IHC4 in HR+/HER2- early breast cancer: WSG-AGO EC
      Doc Trial.
AB  - INTRODUCTION: Potential prognostic and predictive markers in early, intermediate
      risk breast cancer (BC) include histological grade, Ki-67, genomic signatures,
      e.g. genomic grade index (GGI), and intrinsic subtypes. Their
      prognostic/predictive impact in hormone receptor (HR: ER and/or PR) positive/HER2
      BC is controversial. WSG-AGO EC-Doc demonstrated superior event-free survival
      (EFS) in patients with 1-3 positive lymph node receiving
      epirubicin/cyclophosphamide-docetaxel (EC-Doc) versus 5
      fluoruracil/epirubicin/cyclophosphamide (FEC). METHODS: In a representative trial
      subset, we quantify concordance among factors used for clinical chemotherapy
      indication. We investigate the impact of central histology (n = 772),
      immunohistochemistry for intrinsic subtyping and IHC4, and dichotomous (GG) or
      continuous (GGI) genomic grade (n = 472) on patient outcome and benefit from
      taxane chemotherapy, focusing on HR+/HER2- patients (n = 459). RESULTS:
      Concordance of local grade (LG) with central (CG) or genomic grade was modest. In
      HR+/HER2- patients, low (GG-1: 16%), equivocal (GG-EQ: 17%), and high (GG-3: 67%)
      GG were associated with respective 5-year EFS of 100%, 93%, and 85%. GGI was
      prognostic for EFS within all LG subgroups and within CG3, whereas IHC4 was
      prognostic only in CG3 tumors.In unselected and HR+/HER2- patients, CG3 and
      luminal-A-like subtype entered the multivariate EFS model, but not IHC4 or GG. In
      the whole population, continuous GGI entered the model [hazard ratio (H.R.) of
      75th versus 25th = 2.79; P = 0.01], displacing luminal-A-like subtype; within
      HR+/HER2- (H.R. = 5.36; P < 0.001), GGI was the only remaining prognostic
      factor.In multivariate interaction analysis (including central and genomic
      grade), luminal-B-like subtype [HR+ and (Ki-67 >=20% or HER2+)] was predictive
      for benefit of EC-Doc versus FEC in unselected but not in HR+/HER2- patients.
      CONCLUSION: In the WSG-AGO EC-Doc trial for intermediate-risk BC, CG, intrinsic
      subtype (by IHC), and GG provide prognostic information. Continuous GGI (but not
      IHC4) adds prognostic information even when IHC subtype and CG are available.
      Finally, the high interobserver variability for histological grade and the still
      missing validation of Ki-67 preclude indicating or omitting adjuvant chemotherapy
      based on these single factors alone. TRIAL REGISTRATION: The WSG-AGO/EC-Doc is
      registered at ClinicalTrials.gov, NCT02115204.

PMID- 27022070
TI  - The Impact of Gene Expression Patterns in Breast Cancer.

PMID- 27022071
TI  - Understanding variation in human fertility: what can we learn from evolutionary
      demography?
AB  - Decades of research on human fertility has presented a clear picture of how
      fertility varies, including its dramatic decline over the last two centuries in
      most parts of the world. Why fertility varies, both between and within
      populations, is not nearly so well understood. Fertility is a complex phenomenon,
      partly physiologically and partly behaviourally determined, thus an
      interdisciplinary approach is required to understand it. Evolutionary
      demographers have focused on human fertility since the 1980s. The first wave of
      evolutionary demographic research made major theoretical and empirical advances,
      investigating variation in fertility primarily in terms of fitness maximization.
      Research focused particularly on variation within high-fertility populations and
      small-scale subsistence societies and also yielded a number of hypotheses for why
      fitness maximization seems to break down as fertility declines during the
      demographic transition. A second wave of evolutionary demography research on
      fertility is now underway, paying much more attention to the cultural and
      psychological mechanisms underpinning fertility. It is also engaging with the
      complex, multi-causal nature of fertility variation, and with understanding
      fertility in complex modern and transitioning societies. Here, we summarize the
      history of evolutionary demographic work on human fertility, describe the current
      state of the field, and suggest future directions.

PMID- 27022072
TI  - The offspring quantity-quality trade-off and human fertility variation.
AB  - The idea that trade-offs between offspring quantity and quality shape
      reproductive behaviour has long been central to economic perspectives on
      fertility. It also has a parallel and richer theoretical foundation in
      evolutionary ecology. We review the application of the quantity-quality trade-off
      concept to human reproduction, emphasizing distinctions between clutch size and
      lifetime fertility, and the wider set of forces contributing to fertility
      variation in iteroparous and sexually reproducing species like our own. We then
      argue that in settings approximating human evolutionary history, several factors
      limit costly sibling competition. Consequently, while the optimization of
      quantity-quality trade-offs undoubtedly shaped the evolution of human physiology
      setting the upper limits of reproduction, we argue it plays a modest role in
      accounting for socio-ecological and individual variation in fertility. Only upon
      entering the demographic transition can fertility limitation be clearly
      interpreted as strategically orientated to advancing offspring quality via
      increased parental investment per child, with low fertility increasing descendant
      socio-economic success, although not reproductive success. We conclude that
      existing economic and evolutionary literature has often overemphasized the
      centrality of quantity-quality trade-offs to human fertility variation and
      advocate for the development of more holistic frameworks encompassing alternative
      life-history trade-offs and the evolved mechanisms guiding their resolution. 

PMID- 27022075
TI  - Measuring selection in human populations using the growth rate per generation.
AB  - Estimates of the speed of evolution between generations depend on the association
      between individual traits and a measure of fitness. The two most frequently used
      measures of fitness are the net reproduction rate and the 1-year growth factor
      implied by the fertility and mortality rates. Results based on the two lead to
      very different results. The reason is that the 1-year growth factor is not a
      measure of change between generations. Therefore, studies of changes between
      generations should use the amount of growth over the length of a generation. This
      is especially important for studies of human populations because of the long
      length of generation. In addition, estimates based on a single year's growth are
      overly sensitive to data on individuals who fail to reproduce. The effects of
      using a generational measure are demonstrated using data from Kenya and Ukraine.
      These results demonstrate that using a 1-year growth rate to measure fitness
      leads to estimates that understate the rate at which evolution changes the
      characteristics of a human population. 

PMID- 27022073
TI  - Developmental influences on fertility decisions by women: an evolutionary
      perspective.
AB  - Developmental environments are crucial for shaping our life course. Elements of
      the early social and biological environments have been consistently associated
      with reproduction in humans. To date, a strong focus has been on the relationship
      between early stress, earlier menarche and first child birth in women. These
      associations, found predominately in high-income countries, have been usefully
      interpreted within life-history theory frameworks. Fertility, on the other hand-
      a missing link between an individual's early environment, reproductive strategy
      and fitness--has received little attention. Here, we synthesize this literature
      by examining the associations between early adversity, age at menarche and
      fertility and fecundity in women. We examine the evidence that potential
      mechanisms such as birth weight, childhood body composition, risky health
      behaviours and developmental influences on attractiveness link the early
      environment and fecundity and fertility. The evidence that menarche is associated
      with fertility and fecundity is good. Currently, owing to the small number of
      correlational studies and mixed methodologies, the evidence that early adversity
      predicts fecundity and fertility is not conclusive. This area of research is in
      its infancy; studies examining early adversity and adult fertility decisions that
      can also examine likely biological, social and psychological pathways present
      opportunities for future fertility research.

PMID- 27022074
TI  - Why do women stop reproducing before menopause? A life-history approach to age at
      last birth.
AB  - Evolutionary biologists have long considered menopause to be a fundamental puzzle
      in understanding human fertility behaviour, as post-menopausal women are no
      longer physiologically capable of direct reproduction. Menopause typically occurs
      between 45 and 55 years of age, but across cultures and history, women often stop
      reproducing many years before menopause. Unlike age at first reproduction or even
      birth spacing, a woman nearing the end of her reproductive cycle is able to
      reflect upon the offspring she already has--their numbers and phenotypic
      qualities, including sexes. This paper reviews demographic data on age at last
      birth both across and within societies, and also presents a case study of age at
      last birth in rural Bangladeshi women. In this Bangladeshi sample, age at last
      birth preceded age at menopause by an average of 11 years, with marked variation
      around that mean, even during a period of high fertility. Moreover, age at last
      birth was not strongly related to age at menopause. Our literature review and
      case study provide evidence that stopping behaviour needs to be more closely
      examined as an important part of human reproductive strategies and life-history
      theory. Menopause may be a final marker of permanent reproductive cessation, but
      it is only one piece of the evolutionary puzzle.

PMID- 27022076
TI  - What do men want? Re-examining whether men benefit from higher fertility than is
      optimal for women.
AB  - Several empirical observations suggest that when women have more autonomy over
      their reproductive decisions, fertility is lower. Some evolutionary theorists
      have interpreted this as evidence for sexual conflicts of interest, arguing that
      higher fertility is more adaptive for men than women. We suggest the assumptions
      underlying these arguments are problematic: assuming that women suffer higher
      costs of reproduction than men neglects the (different) costs of reproduction for
      men; the assumption that men can repartner is often false. We use simple models
      to illustrate that (i) menorwomen can prefer longer interbirth intervals (IBIs),
      (ii) if men can only partner with wives sequentially they may favour shorter IBIs
      than women, but such a strategy would only be optimal for a few men who can
      repartner. This suggests that an evolved universal male preference for higher
      fertility than women prefer is implausible and is unlikely to fully account for
      the empirical data. This further implies that if women have more reproductive
      autonomy, populations should grow, not decline. More precise theoretical
      explanations with clearly stated assumptions, and data that better address both
      ultimate fitness consequences and proximate psychological motivations, are needed
      to understand under which conditions sexual conflict over reproductive timing
      should arise. 

PMID- 27022077
TI  - Status competition, inequality, and fertility: implications for the demographic
      transition.
AB  - The role that social status plays in small-scale societies suggests that status
      may be important for understanding the evolution of human fertility decisions,
      and for understanding how such decisions play out in modern contexts. This paper
      explores whether modelling competition for status--in the sense of relative rank
      within a society--can help shed light on fertility decline and the demographic
      transition. We develop a model of how levels of inequality and status competition
      affect optimal investment by parents in the embodied capital (health, strength,
      and skills) and social status of offspring, focusing on feedbacks between
      individual decisions and socio-ecological conditions. We find that conditions
      similar to those in demographic transition societies yield increased investment
      in both embodied capital and social status, generating substantial decreases in
      fertility, particularly under conditions of high inequality and intense status
      competition. We suggest that a complete explanation for both fertility variation
      in small-scale societies and modern fertility decline will take into account the
      effects of status competition and inequality.

PMID- 27022078
TI  - The evolved psychological mechanisms of fertility motivation: hunting for
      causation in a sea of correlation.
AB  - Cultural, ecological, familial and physiological factors consistently influence
      fertility behaviours, however, the proximate psychological mechanisms underlying
      fertility decisions in humans are poorly understood. Understanding the
      psychological mechanisms underlying human fertility may illuminate the final
      processes by which some of these known predictors have their influence. To date,
      research into the psychological mechanisms underlying fertility has been
      fragmented. Aspects of reproductive psychology have been examined by researchers
      in a range of fields, but the findings have not been systematically integrated in
      one review. We provide such a review, examining current theories and research on
      psychological mechanisms of fertility. We examine the methods and populations
      used in the research, as well as the disciplines and theoretical perspectives
      from which the work has come. Much of the work that has been done to date is
      methodologically limited to examining correlations between ecological, social and
      economic factors and fertility. We propose, and support with examples, the use of
      experimental methods to differentiate causal factors from correlates. We also
      discuss weaknesses in the experimental research, including limited work with non
      WEIRD (western, educated, industrialized, rich and democratic) populations. 

PMID- 27022079
TI  - The cultural evolution of fertility decline.
AB  - Cultural evolutionists have long been interested in the problem of why fertility
      declines as populations develop. By outlining plausible mechanistic links between
      individual decision-making, information flow in populations and competition
      between groups, models of cultural evolution offer a novel and powerful approach
      for integrating multiple levels of explanation of fertility transitions. However,
      only a modest number of models have been published. Their assumptions often
      differ from those in other evolutionary approaches to social behaviour, but their
      empirical predictions are often similar. Here I offer the first overview of
      cultural evolutionary research on demographic transition, critically compare it
      with approaches taken by other evolutionary researchers, identify gaps and
      overlaps, and highlight parallel debates in demography. I suggest that
      researchers divide their labour between three distinct phases of fertility
      decline--the origin, spread and maintenance of low fertility--each of which may
      be driven by different causal processes, at different scales, requiring different
      theoretical and empirical tools. A comparative, multi-level and mechanistic
      framework is essential for elucidating both the evolved aspects of our psychology
      that govern reproductive decision-making, and the social, ecological and cultural
      contingencies that precipitate and sustain fertility decline.

PMID- 27022080
TI  - Wealth, fertility and adaptive behaviour in industrial populations.
AB  - The lack of association between wealth and fertility in contemporary
      industrialized populations has often been used to question the value of an
      evolutionary perspective on human behaviour. Here, we first present the history
      of this debate, and the evolutionary explanations for why wealth and fertility
      (the number of children) are decoupled in modern industrial settings. We suggest
      that the nature of the relationship between wealth and fertility remains an open
      question because of the multi-faceted nature of wealth, and because existing
      cross-sectional studies are ambiguous with respect to how material wealth and
      fertility are linked. A literature review of longitudinal studies on wealth and
      fertility shows that the majority of these report positive effects of wealth,
      although levels of fertility seem to fall below those that would maximize
      fitness. We emphasize that reproductive decision-making reflects a complex
      interplay between individual and societal factors that resists simple
      evolutionary interpretation, and highlight the role of economic insecurity in
      fertility decisions. We conclude by discussing whether the wealth-fertility
      relationship can inform us about the adaptiveness of modern fertility behaviour,
      and argue against simplistic claims regarding maladaptive behaviour in humans. 

PMID- 27022081
TI  - Evaluating reproductive decisions as discrete choices under social influence.
AB  - Discrete choice, coupled with social influence, plays a significant role in
      evolutionary studies of human fertility, as investigators explore how and why
      reproductive decisions are made. We have previously proposed that the relative
      magnitude of social influence can be compared against the transparency of pay
      off, also known as the transparency of a decision, through a heuristic diagram
      that maps decision-making along two axes. The horizontal axis represents the
      degree to which an agent makes a decision individually versus one that is
      socially influenced, and the vertical axis represents the degree to which there
      is transparency in the pay-offs and risks associated with the decision the agent
      makes. Having previously parametrized the functions that underlie the diagram, we
      detail here how our estimation methods can be applied to real-world datasets
      concerning sexual health and contraception. 

PMID- 27022082
TI  - How does variance in fertility change over the demographic transition?
AB  - Most work on the human fertility transition has focused on declines in mean
      fertility. However, understanding changes in the variance of reproductive
      outcomes can be equally important for evolutionary questions about the
      heritability of fertility, individual determinants of fertility and changing
      patterns of reproductive skew. Here, we document how variance in completed
      fertility among women (45-49 years) differs across 200 surveys in 72 low- to
      middle-income countries where fertility transitions are currently in progress at
      various stages. Nearly all (91%) of samples exhibit variance consistent with a
      Poisson process of fertility, which places systematic, and often severe,
      theoretical upper bounds on the proportion of variance that can be attributed to
      individual differences. In contrast to the pattern of total variance, these upper
      bounds increase from high- to mid-fertility samples, then decline again as
      samples move from mid to low fertility. Notably, the lowest fertility samples
      often deviate from a Poisson process. This suggests that as populations move to
      low fertility their reproduction shifts from a rate-based process to a focus on
      an ideal number of children. We discuss the implications of these findings for
      predicting completed fertility from individual-level variables.

PMID- 27022083
TI  - Pathways from education to fertility decline: a multi-site comparative study.
AB  - Women's education has emerged as a central predictor of fertility decline, but
      the many ways that education affects fertility have not been subject to detailed
      comparative investigation. Taking an evolutionary biosocial approach, we use
      structural equation modelling to examine potential pathways between education and
      fertility including: infant/child mortality, women's participation in the labour
      market, husband's education, social network influences, and contraceptive use or
      knowledge across three very different contexts: Matlab, Bangladesh; San Borja,
      Bolivia; and rural Poland. Using a comparable set of variables, we show that the
      pathways by which education affects fertility differ in important ways, yet also
      show key similarities. For example, we find that across all three contexts,
      education is associated with delayed age at first birth via increasing women's
      labour-force participation, but this pathway only influences fertility in rural
      Poland. In Matlab and San Borja, education is associated with lower local
      childhood mortality, which influences fertility, but this pathway is not
      important in rural Poland. Similarities across sites suggest that there are
      common elements in how education drives demographic transitions cross-culturally,
      but the differences suggest that local socioecologies also play an important role
      in the relationship between education and fertility decline. 

PMID- 27022084
TI  - What if fertility decline is not permanent? The need for an evolutionarily
      informed approach to understanding low fertility.
AB  - 'Demographic transition theory' assumes that fertility decline is irreversible.
      This commonly held assumption is based on observations of recent and historical
      reductions in fertility that accompany modernization and declining mortality. The
      irreversibility assumption, however, is highly suspect from an evolutionary point
      of view, because demographic traits are at least partially influenced by genetics
      and are responsive to social and ecological conditions. Nonetheless, an
      inevitable shift from high mortality and fertility to low mortality and fertility
      is used as a guiding framework for projecting human population sizes into the
      future. This paper reviews some theoretical and empirical evidence suggesting
      that the assumption of irreversibility is ill-founded, at least without
      considerable development in theory that incorporates evolutionary and ecological
      processes. We offer general propositions for how fertility could increase in the
      future, including natural selection on high fertility variants, the difficulty of
      maintaining universal norms and preferences in a large, diverse and economically
      differentiated population, and the escalating resource demands of modernization. 

PMID- 27022085
TI  - Hypertrophic epicardial adipose tissue mimicking a thoracic mass.

PMID- 27022086
TI  - A case of biatrial drainage of the right superior vena cava.
AB  - Biatrial drainage of the right superior vena cava resulting from a sinus venosus
      defect is a rare congenital malformation. It can result in severe desaturation
      although a sinus venosus defect usually presents as a left-to-right shunt. A male
      baby was noted to have cyanosis while nursing and was referred to us for medical
      treatment on his second day of life. Echocardiography showed that most of the
      blood flowing through the superior vena cava drained into the left atrium. He
      underwent successful surgery to correct this defect at the age of 2 years.

PMID- 27022087
TI  - Sophie Dumont: Mastering the uncanny mechanics of living systems.

PMID- 27022088
TI  - Separating neuronal compartments gives clues as to local effect of ubiquitin
      conjugates in synaptogenesis.
AB  - Presynaptic differentiation is a critical and poorly understood step in synapse
      formation. Using compartmentalized culture systems that isolate axons and nascent
      synapses, Pinto et al. (2016. J. Cell Biol.
      http://dx.doi.org/10.1083/jcb.201509039) show that the axonal ubiquitin
      proteasome system locally regulates the accumulation of ubiquitinated substrates,
      triggering presynaptic differentiation.

PMID- 27022089
TI  - On the move, lysosomal CAX drives Ca2+ transport and motility.
AB  - Acidic Ca(2+)stores are important sources of Ca(2+)during cell signaling but
      little is known about how Ca(2+)enters these stores. In this issue, Melchionda et
      al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201510019) identify a
      Ca(2+)/H(+)exchanger (CAX) that is required for Ca(2+)uptake and cell migration
      in vertebrates.

PMID- 27022090
TI  - Shape-motion relationships of centering microtubule asters.
AB  - Although mechanisms that contribute to microtubule (MT) aster positioning have
      been extensively studied, still little is known on how asters move inside cells
      to faithfully target a cellular location. Here, we study sperm aster centration
      in sea urchin eggs, as a stereotypical large-scale aster movement with extreme
      constraints on centering speed and precision. By tracking three-dimensional aster
      centration dynamics in eggs with manipulated shapes, we show that aster geometry
      resulting from MT growth and interaction with cell boundaries dictates aster
      instantaneous directionality, yielding cell shape-dependent centering
      trajectories. Aster laser surgery and modeling suggest that dynein-dependent MT
      cytoplasmic pulling forces that scale to MT length function to convert aster
      geometry into directionality. In contrast, aster speed remains largely
      independent of aster size, shape, or absolute dynein activity, which suggests it
      may be predominantly determined by aster growth rate rather than MT force
      amplitude. These studies begin to define the geometrical principles that control
      aster movements. 

PMID- 27022093
TI  - Return-to-Work Program for Injured Workers: Factors of Successful Return to
      Employment.
AB  - This study examined the factors of successful return to employment among
      participants in the return to work program (RTW) following work-related injury.
      Data were obtained from the Social Security Organization database containing 9850
      injured workers who underwent RTW in 2010 to 2013. About 65% had successfully
      returned to employment. Significant factors of successful return include gender,
      employer interest, motivation, age, intervention duration, and type of injury.
      Male and motivated employees were more likely to return to employment compared
      with female and unmotivated employees, respectively. Participants from interested
      employers were 23.22 times more likely to return to work than those from
      uninterested employers, whereas participants whose intervention period exceeded 5
      months were 41% less likely to return to work compared with those whose
      intervention period was within 3 months. Appropriate strategy and enhanced
      collaboration between the stakeholders would improve the proportion of successful
      return to employment.

PMID- 27022091
TI  - The proteasome controls presynaptic differentiation through modulation of an on
      site pool of polyubiquitinated conjugates.
AB  - Differentiation of the presynaptic terminal is a complex and rapid event that
      normally occurs in spatially specific axonal regions distant from the soma; thus,
      it is believed to be dependent on intra-axonal mechanisms. However, the full
      nature of the local events governing presynaptic assembly remains unknown.
      Herein, we investigated the involvement of the ubiquitin-proteasome system (UPS),
      the major degradative pathway, in the local modulation of presynaptic
      differentiation. We found that proteasome inhibition has a synaptogenic effect on
      isolated axons. In addition, formation of a stable cluster of synaptic vesicles
      onto a postsynaptic partner occurs in parallel to an on-site decrease in
      proteasome degradation. Accumulation of ubiquitinated proteins at nascent sites
      is a local trigger for presynaptic clustering. Finally, proteasome-related
      ubiquitin chains (K11 and K48) function as signals for the assembly of
      presynaptic terminals. Collectively, we propose a new axon-intrinsic mechanism
      for presynaptic assembly through local UPS inhibition. Subsequent on-site
      accumulation of proteins in their polyubiquitinated state triggers formation of
      presynapses. 

PMID- 27022092
TI  - G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate
      with 40S subunits.
AB  - Mammalian stress granules (SGs) contain stalled translation preinitiation
      complexes that are assembled into discrete granules by specific RNA-binding
      proteins such as G3BP. We now show that cells lacking both G3BP1 and G3BP2 cannot
      form SGs in response to eukaryotic initiation factor 2alpha phosphorylation or
      eIF4A inhibition, but are still SG-competent when challenged with severe heat or
      osmotic stress. Rescue experiments using G3BP1 mutants show that phosphomimetic
      G3BP1-S149E fails to rescue SG formation, whereas G3BP1-F33W, a mutant unable to
      bind G3BP partner proteins Caprin1 or USP10, rescues SG formation. Caprin1/USP10
      binding to G3BP is mutually exclusive: Caprin binding promotes, but USP10 binding
      inhibits, SG formation. G3BP interacts with 40S ribosomal subunits through its
      RGG motif, which is also required for G3BP-mediated SG formation. We propose that
      G3BP mediates the condensation of SGs by shifting between two different states
      that are controlled by the phosphorylation of S149 and by binding to Caprin1 or
      USP10. 

PMID- 27022094
TI  - Derivatives of usnic acid inhibit broad range of influenza viruses and protect
      mice from lethal influenza infection.
AB  - BACKGROUND: Influenza is a disease of significant morbidity and mortality, the
      number of anti-influenza drugs is small; many of them stimulate the appearance of
      resistant strains. In this work, we demonstrate activity of some usnic acid (UA)
      derivatives against influenza virus in vitro and in vivo. METHODS: Organic
      synthesis was used to prepare compounds. Antiviral activity of the compounds in
      vitro was evaluated by their ability to decrease the virus titer on Madin-Darby
      Canine Kidney cells. In vivo activity was evaluated by decrease of mortality and
      index of protection. RESULTS: Compounds were tested against a broad spectrum of
      influenza virus strains and showed activity against all used strains. One
      compound, [5] (valine enamine of UA), also significantly reduced lethality of
      infected animals and does not give rise to the appearance of resistant strains.
      Additional studies showed that hepatotoxicity of compound [5] is reduced
      comparatively to UA. CONCLUSION: Our results suggest that valine enamine of UA
      could be a potential candidate for the development of a new anti-influenza
      therapy.

PMID- 27022095
TI  - The Impact of Real-Time Continuous Glucose Monitoring in Patients 65 Years and
      Older.
AB  - BACKGROUND: Older adults with type 1 diabetes (T1D) or insulin-using type 2
      diabetes (iT2D) are at high risk for severe hypoglycemic episodes. Real-time
      continuous glucose monitoring (RT-CGM) in this population may reduce this risk,
      but when patients switch to Medicare at age 65, RT-CGM is no longer a covered
      benefit. We developed a survey to examine health and quality of life (QOL)
      benefits of RT-CGM in seniors (age >= 65). METHODS: Two groups of seniors with
      T1D or iT2D-current RT-CGM users (n = 210) and RT-CGM "hopefuls" (patients who
      wanted but could not obtain RT-CGM due to lack of insurance coverage; n = 75)
      completed an online survey. The survey examined history of hypoglycemic
      experiences as well as current quality of life (QOL), including generic and
      diabetes-specific measures. RESULTS: Current users reported fewer moderate (P <
      .01) and fewer severe hypoglycemic episodes (P < .01) over the past 6 months than
      "hopefuls" and greater reductions over time in hypoglycemic events requiring the
      assistance of another, ER visits, and paramedic visits to the home (in all cases,
      P < .01). Regarding QOL, current users reported significantly better well-being
      (P < .001), less hypoglycemic fear (P < .05), and less diabetes distress (P <
      .05) than "hopefuls." CONCLUSIONS: These data suggest that RT-CGM use in seniors
      is associated with reductions in episodes of severe hypoglycemia and improved
      QOL, suggesting that restrictive access to RT-CGM in the Medicare age population
      may have deleterious health, economic, and QOL consequences.

PMID- 27022098
TI  - Benefits, Challenges, and Potential Utility of a Gait Database for Diabetes
      Patients.
AB  - Gait analysis is a useful tool in understanding movement impairments, which
      impact on patient well-being. The use of gait analysis in patients with diabetes
      has led to improvements in health care including the treatment and prevention of
      ulceration and development of targeted exercise interventions. The current
      convention when analyzing gait is to address specific complications of diabetes,
      controlling for potential influencing conditions within a study sample to
      understand the effects of the few specific complications chosen for analysis.
      Databases allow for the storage of data in a structured format, allowing easy
      access to large quantities of data in a consistent, comparable manner. A database
      of gait analyses of patients with diabetes has the potential to include far
      greater sample sizes for statistical analyses, allowing multiple influencing
      factors to be assessed simultaneously, and relationships identified between
      multiple influencing factors. However, a database of this type would encounter
      ethical and methodological challenges in its implementation, which are discussed.
      This article introduces some of the potential benefits, challenges, and utility
      of a gait database for diabetes patients. We highlight that, whereas the creation
      of a database within this clinical population would be a complex process both
      ethically and practically, huge potential benefits could be gained, overcoming
      some of the limitations faced by traditional isolated gait analysis studies.

PMID- 27022096
TI  - Influences on Technology Use and Efficacy in Type 1 Diabetes.
AB  - The majority of people with type 1 diabetes have suboptimal glycemic control,
      increasing their complication risk. Technology to support diabetes self-care has
      advanced significantly and includes self-monitoring of blood glucose (SMBG),
      insulin pump therapy (IPT), continuous glucose monitoring (CGM), and sensor
      augmented pump therapy (SAPT), which are stepping stones toward the "artificial
      pancreas" using closed-loop technology. Use of these technologies improves
      clinical outcomes for patients with the appropriate skills and motivation. This
      review addresses the psychosocial factors that influence both technology
      provision and clinical outcome and also how technology impacts on psychological
      outcomes. Optimal use of the various diabetes self-management technologies is
      influenced by previous self-care behaviors, demographic and psychological
      factors. Provision of IPT is also influenced by the same factors. Despite
      technology increasing the complexity of treatment, the lack of evidence for
      adverse psychological outcomes is reassuring. Treatment satisfaction is high, and
      discontinuation rates are low. However, technology will widen the health
      inequality gap if its use is limited to motivated patients who demonstrate good
      self-care behaviors. Pivotal to the success of the various technologies is
      provision of appropriate education at initiation of the technology, regular
      ongoing contact for treatment adjustments and trouble-shooting device issues plus
      access to psychological support when required. Additional support strategies may
      be required to help patients struggling with their diabetes to benefit from the
      available technology, recognizing that they may have most to gain.

PMID- 27022099
TI  - Erratum for Alfano et al., Episodic Diversifying Selection Shaped the Genomes of
      Gibbon Ape Leukemia Virus and Related Gammaretroviruses.

PMID- 27022097
TI  - Reducing Glucose Variability Due to Meals and Postprandial Exercise in T1DM Using
      Switched LPV Control: In Silico Studies.
AB  - BACKGROUND: Time-varying dynamics is one of the main issues for achieving safe
      blood glucose control in type 1 diabetes mellitus (T1DM) patients. In addition,
      the typical disturbances considered for controller design are meals, which
      increase the glucose level, and physical activity (PA), which increases the
      subject's sensitivity to insulin. In previous works the authors have applied a
      linear parameter-varying (LPV) control technique to manage unannounced meals.
      METHODS: A switched LPV controller that switches between 3 LPV controllers, each
      with a different level of aggressiveness, is designed to further cope with both
      unannounced meals and postprandial PA. Thus, the proposed control strategy has a
      "standard" mode, an "aggressive" mode, and a "conservative" mode. The "standard"
      mode is designed to be applied most of the time, while the "aggressive" mode is
      designed to deal only with hyperglycemia situations. On the other hand, the
      "conservative" mode is focused on postprandial PA control. RESULTS: An ad hoc
      simulator has been developed to test the proposed controller. This simulator is
      based on the distribution version of the UVA/Padova model and includes the effect
      of PA based on Schiavon.(1) The test results obtained when using this simulator
      indicate that the proposed control law substantially reduces the risk of
      hypoglycemia with the conservative strategy, while the risk of hyperglycemia is
      scarcely affected. CONCLUSIONS: It is demonstrated that the announcement, or
      anticipation, of exercise is indispensable for letting a mono-hormonal artificial
      pancreas deal with the consequences of postprandial PA. In view of this the
      proposed controller allows switching into a conservative mode when notified of PA
      by the user.

PMID- 27022100
TI  - Correction for Rossetto et al., Regulation of Viral and Cellular Gene Expression
      by Kaposi's Sarcoma-Associated Herpesvirus Polyadenylated Nuclear RNA.

PMID- 27022101
TI  - Correction for Thaa et al., Differential Phosphatidylinositol-3-Kinase-Akt-mTOR
      Activation by Semliki Forest and Chikungunya Viruses Is Dependent on nsP3 and
      Connected to Replication Complex Internalization.

PMID- 27022104
TI  - Society of Toxicology Board of Publications Best Paper Award for 2016.

PMID- 27022105
TI  - Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in
      Mice.
AB  - The liver performs a variety of unique functions critical for metabolic
      homeostasis. Here, we show that mice lacking the splicing factor SRSF2 but not
      SRSF1 in hepatocytes have severe liver pathology and biochemical abnormalities.
      Histological analyses revealed generalized hepatitis with the presence of
      ballooned hepatocytes and evidence of fibrosis. Molecular analysis demonstrated
      that SRSF2 governs splicing of multiple genes involved in the stress-induced cell
      death pathway in the liver. More importantly, SRSF2 also functions as a potent
      transcription activator, required for efficient expression of transcription
      factors mainly responsible for energy homeostasis and bile acid metabolism in the
      liver. Consistent with the effects of SRSF2 in gene regulation, accumulation of
      total cholesterol and bile acids was prominently observed in the mutant liver,
      followed by enhanced generation of reactive oxygen species and increased
      endoplasmic reticulum stress, as revealed by biochemical and ultrastructural
      analyses. Taking these observations together, inactivation of SRSF2 in liver
      caused dysregulated splicing events and hepatic metabolic disorders, which
      trigger endoplasmic reticulum stress, oxidative stress, and finally liver
      failure.

PMID- 27022106
TI  - Impact of treated wastewater on growth, respiration and hydraulic conductivity of
      citrus root systems in light and heavy soils.
AB  - Roots interact with soil properties and irrigation water quality leading to
      changes in root growth, structure and function. We studied these interactions in
      an orchard and in lysimeters with clay and sandy loam soils. Minirhizotron
      imaging and manual sampling showed that root growth was three times lower in the
      clay relative to sandy loam soil. Treated wastewater (TWW) led to a large
      reduction in root growth with clay (45-55%) but not with sandy loam soil (<20%).
      Treated wastewater increased salt uptake, membrane leakage and proline content,
      and decreased root viability, carbohydrate content and osmotic potentials in the
      fine roots, especially in clay. These results provide evidence that TWW
      challenges and damages the root system. The phenology and physiology of root
      orders were studied in lysimeters. Soil type influenced diameter, specific root
      area, tissue density and cortex area similarly in all root orders, while TWW
      influenced these only in clay soil. Respiration rates were similar in both soils,
      and root hydraulic conductivity was severely reduced in clay soil. Treated
      wastewater increased respiration rate and reduced hydraulic conductivity of all
      root orders in clay but only of the lower root orders in sandy loam soil. Loss of
      hydraulic conductivity increased with root order in clay and clay irrigated with
      TWW. Respiration and hydraulic properties of all root orders were significantly
      affected by sodium-amended TWW in sandy loam soil. These changes in root order
      morphology, anatomy, physiology and hydraulic properties indicate rapid and major
      modifications of root systems in response to differences in soil type and water
      quality.

PMID- 27022109
TI  - At the Heart of Adolescent and Young Adult Cancer Survivorship.

PMID- 27022107
TI  - Delineation of Molecular Pathways Involved in Cardiomyopathies Caused by Troponin
      T Mutations.
AB  - Familial hypertrophic cardiomyopathy (FHC) is associated with mild to severe
      cardiac problems and is the leading cause of sudden death in young people and
      athletes. Although the genetic basis for FHC is well-established, the molecular
      mechanisms that ultimately lead to cardiac dysfunction are not well understood.
      To obtain important insights into the molecular mechanism(s) involved in FHC,
      hearts from two FHC troponin T models (Ile79Asn [I79N] and Arg278Cys [R278C])
      were investigated using label-free proteomics and metabolomics. Mutations in
      troponin T are the third most common cause of FHC, and the I79N mutation is
      associated with a high risk of sudden cardiac death. Most FHC-causing mutations,
      including I79N, increase the Ca(2+) sensitivity of the myofilament; however, the
      R278C mutation does not alter Ca(2+) sensitivity and is associated with a better
      prognosis than most FHC mutations. Out of more than 1200 identified proteins, 53
      and 76 proteins were differentially expressed in I79N and R278C hearts,
      respectively, when compared with wild-type hearts. Interestingly, more than 400
      proteins were differentially expressed when the I79N and R278C hearts were
      directly compared. The three major pathways affected in I79N hearts relative to
      R278C and wild-type hearts were the ubiquitin-proteasome system, antioxidant
      systems, and energy production pathways. Further investigation of the proteasome
      system using Western blotting and activity assays showed that proteasome
      dysfunction occurs in I79N hearts. Metabolomic results corroborate the proteomic
      data and suggest the glycolytic, citric acid, and electron transport chain
      pathways are important pathways that are altered in I79N hearts relative to R278C
      or wild-type hearts. Our findings suggest that impaired energy production and
      protein degradation dysfunction are important mechanisms in FHCs associated with
      poor prognosis and that cardiac hypertrophy is not likely needed for a switch
      from fatty acid to glucose metabolism.

PMID- 27022110
TI  - Mammographic Density as a Biosensor of Tamoxifen Effectiveness in Adjuvant
      Endocrine Treatment of Breast Cancer: Opportunities and Implications.

PMID- 27022111
TI  - Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in
      Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the
      Suppression of Ovarian Function Trial.
AB  - PURPOSE: The Suppression of Ovarian Function trial showed improved disease
      control for tamoxifen plus ovarian function suppression (OFS) compared with
      tamoxifen alone for the cohort of premenopausal patients who received prior
      chemotherapy. We present the patient-reported outcomes. PATIENTS AND METHODS: The
      quality-of-life (QoL) analysis includes 1,722 of 2,045 premenopausal patients
      with hormone receptor-positive breast cancer randomly assigned to receive
      adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone.
      Chemotherapy use before enrollment was optional. Patients completed a QoL form
      consisting of global and symptom indicators at baseline, every 6 months for 24
      months, and annually during years 3 to 6. Differences in the change of QoL from
      baseline between the two treatments were tested at 6, 24, and 60 months with
      mixed models for repeated measures with and without chemotherapy and overall.
      RESULTS: Patients on tamoxifen plus OFS were more affected than patients on
      tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and
      sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without
      prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge
      over the 5 years than patients on tamoxifen plus OFS. Symptom-specific treatment
      differences at 6 months were less pronounced in patients with prior chemotherapy.
      Changes in global QoL indicators from baseline were small and similar between
      treatments over the whole treatment period. CONCLUSION: Overall, OFS added to
      tamoxifen resulted in worse endocrine symptoms and sexual functioning during the
      first 2 years of treatment, with variable magnitudes of treatment differences.
      Short-term differences in symptom-specific QoL, treatment burden, and coping
      effort between treatment groups were less pronounced for patients with prior
      chemotherapy, the cohort that benefited most from OFS in terms of disease
      control.

PMID- 27022112
TI  - Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With
      Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase has been an
      important target for non-small-cell lung cancer. Several EGFR tyrosine kinase
      inhibitors (TKIs) are currently approved, and both gefitinib and erlotinib are
      the most well-known first-generation EGFR-TKIs. This randomized phase III study
      was conducted to investigate the difference between these two EGFR-TKIs. PATIENTS
      AND METHODS: Previously treated patients with lung adenocarcinoma were randomly
      assigned to receive gefitinib or erlotinib. This study aimed to investigate the
      noninferiority of gefitinib compared with erlotinib. The primary end point was
      progression-free survival (PFS). RESULTS: Five hundred sixty-one patients were
      randomly assigned, including 401 patients (71.7%) with EGFR mutation. All
      baseline factors (except performance status) were balanced between the arms.
      Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and
      7.5 months (hazard ratio [HR], 1.125; 95% CI, 0.940 to 1.347; P = .257) and 22.8
      and 24.5 months (HR, 1.038; 95% CI, 0.833 to 1.294; P = .768), respectively. The
      response rates for gefitinib and erlotinib were 45.9% and 44.1%, respectively.
      Median PFS times in EGFR mutation-positive patients receiving gefitinib versus
      erlotinib were 8.3 and 10.0 months, respectively (HR, 1.093; 95% CI, 0.879 to
      1.358; P = .424). The primary grade 3 or 4 toxicities were rash (2.2% for
      gefitinib v 18.1% for erlotinib) and alanine aminotransferase (ALT)/aspartate
      aminotransferase (AST) elevation (6.1%/13.0% for gefitinib v 2.2%/3.3% for
      erlotinib). CONCLUSION: The study did not demonstrate noninferiority of gefitinib
      compared with erlotinib in terms of PFS in patients with lung adenocarcinoma
      according to the predefined criteria.

PMID- 27022113
TI  - Acupuncture As an Integrative Approach for the Treatment of Hot Flashes in Women
      With Breast Cancer: A Prospective Multicenter Randomized Controlled Trial
      (AcCliMaT).
AB  - PURPOSE: To determine the effectiveness of acupuncture for the management of hot
      flashes in women with breast cancer. PATIENTS AND METHODS: We conducted a
      pragmatic, randomized controlled trial comparing acupuncture plus enhanced self
      care versus enhanced self-care alone. A total of 190 women with breast cancer
      were randomly assigned. Random assignment was performed with stratification for
      hormonal therapy; the allocation ratio was 1:1. Both groups received a booklet
      with information about climacteric syndrome and its management to be followed for
      at least 12 weeks. In addition, the acupuncture group received 10 traditional
      acupuncture treatment sessions involving needling of predefined acupoints. The
      primary outcome was hot flash score at the end of treatment (week 12), calculated
      as the frequency multiplied by the average severity of hot flashes. The secondary
      outcomes were climacteric symptoms and quality of life, measured by the Greene
      Climacteric and Menopause Quality of Life scales. Health outcomes were measured
      for up to 6 months after treatment. Expectation and satisfaction of treatment
      effect and safety were also evaluated. We used intention-to-treat analyses.
      RESULTS: Of the participants, 105 were randomly assigned to enhanced self-care
      and 85 to acupuncture plus enhanced self-care. Acupuncture plus enhanced self
      care was associated with a significantly lower hot flash score than enhanced self
      care at the end of treatment (P < .001) and at 3- and 6-month post-treatment
      follow-up visits (P = .0028 and .001, respectively). Acupuncture was also
      associated with fewer climacteric symptoms and higher quality of life in the
      vasomotor, physical, and psychosocial dimensions (P < .05). CONCLUSION:
      Acupuncture in association with enhanced self-care is an effective integrative
      intervention for managing hot flashes and improving quality of life in women with
      breast cancer.

PMID- 27022114
TI  - Strategies for Empiric Management of Pediatric Fever and Neutropenia in Patients
      With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic
      Review of Randomized Trials.
AB  - PURPOSE: To describe treatment failure and mortality rates with different
      antibiotic regimens and different management strategies for empirical treatment
      of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic
      stem-cell transplantation (HSCT) recipients. METHODS: We conducted a systematic
      review and performed searches of MEDLINE, Embase, PubMed, and Cochrane Central
      Register of Controlled Trials. Studies were included if pediatric patients had
      cancer or were HSCT recipients and the intervention was related to the management
      of FN. Strategies synthesized were monotherapy versus aminoglycoside-containing
      combination therapy; antipseudomonal penicillin monotherapy versus fourth
      generation cephalosporin monotherapy; inpatient versus outpatient management;
      oral versus intravenous antibiotics; and addition of colony-stimulating factors.
      RESULTS: Of 11,469 citations screened, 68 studies randomly assigning 7,265
      episodes were included. When compared with monotherapy, aminoglycoside-containing
      combination therapy did not decrease treatment failures (risk ratio, 1.13; 95%
      CI, 0.92 to 1.38; P = 0.23), and no difference in mortality was observed.
      Antipseudomonal penicillin and fourth-generation cephalosporin monotherapy were
      associated with similar failure and mortality rates. Outpatient management and
      oral antibiotics were safe in low-risk FN with no infection-related mortality
      observed in any patient and no significant differences in outcomes compared with
      inpatient management and intravenous therapy. Therapeutic colony-stimulating
      factors were associated with a 1.42-day reduction in hospitalization (95% CI,
      0.62 to 2.22 days; P < .001). CONCLUSION: There were a moderate number of
      pediatric randomized trials of FN management. Monotherapy for high-risk FN and
      outpatient and oral management for low-risk FN are effective strategies. These
      findings will provide the basis for guideline recommendations in pediatric FN.

PMID- 27022115
TI  - National Trends in Nonoperative Management of Rectal Adenocarcinoma.
AB  - PURPOSE: Neoadjuvant chemoradiation for stage II/III rectal cancer results in up
      to 49% of patients with a clinical complete response. As a result, many have
      questioned whether surgery can be omitted for this group of patients. Currently,
      there is insufficient evidence for chemoradiation only, or nonoperative
      management (NOM), to support its adoption. Despite this, anecdotal evidence
      suggests there is a trend toward increased use of NOM. Our objective was to
      examine the use of NOM for rectal cancer over time, as well as the patient- and
      facility-level factors associated with its use. METHODS: We included all incident
      cases of invasive, nonmetastatic rectal adenocarcinoma reported to the National
      Cancer Database from 1998 to 2010. We performed univariate and multivariate
      analyses to assess for NOM use over time, as well as associated patient- and
      facility-level factors. RESULTS: A total of 146,135 patients met the inclusion
      criteria: 5,741 had NOM and 140,394 had surgery with or without additional
      therapy. From 1998 to 2010, NOM doubled, from 2.4% to 5% of all cases annually.
      Patients who were black (adjusted odds ratio [AOR], 1.71; 95% CI, 1.57 to 1.86),
      uninsured (AOR, 2.35; 95% CI, 2.08 to 2.65) or enrolled in Medicaid (AOR, 2.10;
      95% CI, 1.90 to 2.33), or treated at low-volume facilities (AOR, 1.53; 95% CI,
      1.42 to 1.64) were more likely to receive NOM than were patients who were white,
      privately insured, and treated at a high-volume facility, respectively.
      CONCLUSION: NOM demonstrates promise for the treatment of rectal cancer;
      currently, however, the most appropriate strategy is to pursue this approach with
      well-informed patients in the context of a clinical trial. We observed evidence
      of increasing NOM use, with this increase occurring more frequently in black and
      uninsured/Medicaid patients, raising concern that increased NOM use may actually
      represent increasing disparities in rectal cancer care rather than innovation.
      Further studies are needed to assess survival differences by treatment strategy.

PMID- 27022116
TI  - Risk of Adverse Health and Social Outcomes Up to 50 Years After Wilms Tumor: The
      British Childhood Cancer Survivor Study.
AB  - PURPOSE: Survivors of Wilms tumor (WT) are at risk for adverse health and social
      outcomes but risks beyond 30 years from diagnosis remain uncertain. We
      investigated the risks of adverse outcomes among 5-year survivors of WT, in
      particular, those between 30 and 50 years from diagnosis. PATIENTS AND METHODS:
      The British Childhood Cancer Survivor Study includes 1,441 5-year survivors of
      WT. We investigated cause-specific mortality, risk of subsequent primary
      neoplasms (SPNs), and, for those who completed a questionnaire, the extent of
      smoking and drinking, educational achievement, health status, and health service
      use compared with the general population. RESULTS: Cumulative risk of death from
      all causes, excluding recurrence, increased substantially from 5.4% to 22.7% at
      30 years and 50 years, respectively, after WT diagnosis-75% of excess deaths
      beyond 30 years from diagnosis were attributable to SPNs (50%) and cardiac
      diseases (25%). Digestive cancer, most frequently bowel, accounted for 41% of
      excess cancers beyond 30 years. CONCLUSION: Between 30 and 50 years from
      diagnosis, survivors of WT are at a substantially increased risk of premature
      mortality, and 75% of excess deaths were accounted for by SPNs and cardiac
      diseases. Radiotherapy exposure was a risk factor for both outcomes. The
      proportion of patients with WT who are exposed to radiotherapy has reduced
      substantially in recent decades because of initiatives such as the SIOP WT 2001
      clinical trial, which sought to reduce late effects; however, the majority of
      current survivors, who are at least 30 years from diagnosis, received
      radiotherapy. Surveillance of this group should focus on SPNs, in particular,
      bowel and breast cancers, and cardiac conditions.

PMID- 27022117
TI  - Reliable Detection of Mismatch Repair Deficiency in Colorectal Cancers Using
      Mutational Load in Next-Generation Sequencing Panels.
AB  - PURPOSE: Tumor screening for Lynch syndrome is recommended in all or most
      patients with colorectal cancer (CRC). In metastatic CRC, sequencing of RAS/BRAF
      is necessary to guide clinical management. We hypothesized that a next-generation
      sequencing (NGS) panel that identifies RAS/BRAF and other actionable mutations
      could also reliably identify tumors with DNA mismatch repair protein deficiency
      (MMR-D) on the basis of increased mutational load. METHODS: We identified all
      CRCs that underwent genomic mutation profiling with a custom NGS assay (MSK
      IMPACT) between March 2014 and July 2015. Tumor mutational load, with exclusion
      of copy number changes, was determined for each case and compared with MMR status
      as determined by routine immunohistochemistry. RESULTS: Tumors from 224 patients
      with unique CRC analyzed for MMR status also underwent MSK-IMPACT. Thirteen
      percent (n = 28) exhibited MMR-D by immunohistochemistry. Using the 341-gene
      assay, 100% of the 193 tumors with < 20 mutations were MMR-proficient. Of 31
      tumors with >= 20 mutations, 28 (90%) were MMR-D. The three remaining tumors were
      easily identified as being distinct from the MMR-D tumors with > 150 mutations
      each. Each of these tumors harbored the P286R hotspot POLE mutation consistent
      with the ultramutator phenotype. Among MMR-D tumors, the median number of
      mutations was 50 (range, 20 to 90) compared with six (range, 0 to 17) in MMR
      proficient/POLE wild-type tumors (P < .001). With a mutational load cutoff of >=
      20 and < 150 for MMR-D detection, sensitivity and specificity were both 1.0 (95%
      CI, 0.93 to 1.0). CONCLUSION: A cutoff for mutational load can be identified via
      multigene NGS tumor profiling, which provides a highly accurate means of
      screening for MMR-D in the same assay that is used for tumor genotyping.

PMID- 27022119
TI  - Another Breast Cancer Entity Confirmed: Genomics of Invasive Lobular Breast
      Cancer.

PMID- 27022118
TI  - Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced
      ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014.
AB  - PURPOSE: Intracranial efficacy of first-line crizotinib versus chemotherapy was
      compared prospectively in the phase III PROFILE 1014 study in ALK-positive non
      small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to
      receive crizotinib (250 mg twice daily; n = 172) or chemotherapy (pemetrexed 500
      mg/m(2) plus cisplatin 75 mg/m(2) or carboplatin at area under the curve 5 to 6,
      every 3 weeks for <= six cycles; n = 171). Patients with stable treated brain
      metastases (tBM) were eligible. Intracranial efficacy was assessed at baseline
      and every 6 or 12 weeks in patients with or without known brain metastases (BM),
      respectively; intracranial time to tumor progression (IC-TTP; per protocol) and
      intracranial disease control rate (IC-DCR; post hoc) were measured. The intent-to
      treat population was also assessed. RESULTS: Of 343 patients in the intent-to
      treat population, 23% had tBM at baseline. A nonsignificant IC-TTP improvement
      was observed with crizotinib in the intent-to-treat population (hazard ratio
      [HR], 0.60; P = .069), patients with tBM (HR, 0.45; P = .063), and patients
      without BM (HR, 0.69; P = .323). Among patients with tBM, IC-DCR was
      significantly higher with crizotinib versus chemotherapy at 12 weeks (85% v 45%,
      respectively; P < .001) and 24 weeks (56% v 25%, respectively; P = .006).
      Progression-free survival was significantly longer with crizotinib versus
      chemotherapy in both subgroups (tBM present: HR, 0.40; P < .001; median, 9.0 v
      4.0 months, respectively; BM absent: HR, 0.51; P < .001; median, 11.1 v 7.2
      months, respectively) and in the intent-to-treat population (HR, 0.45; P < .001;
      median, 10.9 v 7.0 months, respectively). CONCLUSION: Compared with chemotherapy,
      crizotinib demonstrated a significantly higher IC-DCR in patients with tBM.
      Improvements in IC-TTP were not statistically significant in patients with or
      without tBM, although sensitivity to detect treatment differences in or between
      the two subgroups was low.

PMID- 27022120
TI  - Financial Strain and Cancer Outcomes.

PMID- 27022121
TI  - Striving Toward a Cure for Prostate Cancer.

PMID- 27022123
TI  - A Case of Atypical Urticaria.

PMID- 27022122
TI  - Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and
      Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation
      Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227.
AB  - PURPOSE: This study investigated the treatment of primary CNS lymphoma with
      methotrexate, temozolomide (TMZ), and rituximab, followed by hyperfractionated
      whole-brain radiotherapy (hWBRT) and subsequent TMZ. The primary phase I end
      point was the maximum tolerated dose of TMZ. The primary phase II end point was
      the 2-year overall survival (OS) rate. Secondary end points were preirradiation
      response rates, progression-free survival (PFS), neurologic toxicities, and
      quality of life. PATIENTS AND METHODS: The phase I study increased TMZ doses from
      100 to 150 to 200 mg/m(2). Patients were treated with rituximab 375 mg/m(2) 3
      days before cycle 1; methotrexate 3.5 g/m(2) with leucovorin on weeks 1, 3, 5, 7,
      and 9; TMZ daily for 5 days on weeks 4 and 8; hWBRT 1.2 Gy twice-daily on weeks
      11 to 13 (36 Gy); and TMZ 200 mg/m(2) daily for 5 days every 28 days on weeks 14
      to 50. RESULTS: Thirteen patients (one ineligible) were enrolled in phase I of
      the study. The maximum tolerated dose of TMZ was 100 mg/m(2). Dose-limiting
      toxicities were hepatic and renal. In phase II, 53 patients were treated. Median
      follow-up for living eligible patients was 3.6 years, and 2-year OS and PFS were
      80.8% and 63.6%, respectively. Compared with historical controls from RTOG-9310,
      2-year OS and PFS were significantly improved (P = .006 and .030, respectively).
      In phase II, the objective response rate was 85.7%. Among patients, 66% (35 of
      53) had grade 3 and 4 toxicities before hWBRT, and 45% (24 of 53) of patients
      experienced grade 3 and 4 toxicities attributable to post-hWBRT chemotherapy.
      Cognitive function and quality of life improved or stabilized after hWBRT.
      CONCLUSION: This regimen is safe, with the best 2-year OS and PFS achieved in any
      Radiation Therapy Oncology Group primary CNS lymphoma trial. Randomized trials
      that incorporate this regimen are needed to determine its efficacy compared with
      other strategies.

PMID- 27022124
TI  - Commentary.

PMID- 27022125
TI  - Commentary.

PMID- 27022126
TI  - Expected Dangerously Low Potassium Concentrations.

PMID- 27022127
TI  - Selenium Overload?

PMID- 27022129
TI  - The Foxes and the Hedgehogs, Yet Again.

PMID- 27022130
TI  - Biology and management of ependymomas.
AB  - Ependymomas are rare primary tumors of the central nervous system in children and
      adults that comprise histologically similar but genetically distinct subgroups.
      The tumor biology is typically more associated with the site of origin rather
      than being age-specific. Genetically distinct subgroups have been identified by
      genomic studies based on locations in classic grade II and III ependymomas. They
      are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion,
      infratentorial ependymomas with or without a hypermethylated phenotype (CIMP),
      and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have
      different biology than ependymomas with typical WHO grade II or III histology.
      Surgery and radiotherapy are the mainstays of treatment, while the role of
      chemotherapy has not yet been established. An in-depth understanding of tumor
      biology, developing reliable animal models that accurately reflect tumor molecule
      features, and high throughput drug screening are essential for developing new
      therapies. Collaborative efforts between scientists, physicians, and advocacy
      groups will enhance the translation of laboratory findings into clinical trials.
      Improvements in disease control underscore the need to incorporate assessment and
      management of patients' symptoms to ensure that treatment advances translate into
      improvement in quality of life.

PMID- 27022131
TI  - Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53
      ubiquitination in pediatric patients with recurrent or progressive central
      nervous system tumors: A Pediatric Brain Tumor Consortium Study.
AB  - BACKGROUND: p53 is a promising target in human cancer. p28 is a cell-penetrating
      peptide that preferentially enters cancer cells and binds to both wild-type and
      mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal
      degradation. This results in increased levels of p53, which induces cell cycle
      arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated
      dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics
      (PKs) of p28 in children. METHODS: Children aged 3-21 years with recurrent or
      progressive central nervous system tumors were eligible. Intravenous p28 was
      administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16
      mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design.
      Expression status of p53 was characterized by immunohistochemistry, and serum PK
      parameters were established on the second dose. RESULTS: Of the 18 eligible
      patients enrolled in the study, 12 completed the DLT monitoring period and were
      evaluable for toxicity. p28 was well-tolerated; 7 participants received >=2
      courses, and the most common adverse event attributed to the drug was transient
      grade 1 infusion-related reaction. PK analysis revealed a profile similar to
      adults; however, an increased area under the curve was observed in pediatric
      patients. High p53 expression in tumor cell nuclei was observed in 6 of 12
      available tissue samples. There were no objective responses; 2 participants
      remained stable on the study for >4 cycles. CONCLUSIONS: This phase I study
      demonstrated that p28 is well-tolerated in children with recurrent CNS
      malignancies at the adult recommended phase II dose.

PMID- 27022132
TI  - Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in
      experimental glioblastoma.
AB  - BACKGROUND: In glioblastoma (GBM), Id1 serves as a functional marker for self
      renewing cancer stem-like cells. We investigated the mechanism by which
      cyclooxygenase-2 (Cox-2)-derived prostaglandin E2 (PGE2) induces Id1 and
      increases GBM self-renewal and radiation resistance. METHODS: Mouse and human GBM
      cells were stimulated with dimethyl-PGE2 (dmPGE2), a stabilized form of PGE2, to
      test for Id1 induction. To elucidate the signal transduction pathway governing
      the increase in Id1, a combination of short interfering RNA knockdown and small
      molecule inhibitors and activators of PGE2 signaling were used. Western blotting,
      quantitative real-time (qRT)-PCR, and chromatin immunoprecipitation assays were
      employed. Sphere formation and radiation resistance were measured in cultured
      primary cells. Immunohistochemical analyses were carried out to evaluate the Cox
      2-Id1 axis in experimental GBM. RESULTS: In GBM cells, dmPGE2 stimulates the EP4
      receptor leading to activation of ERK1/2 MAPK. This leads, in turn, to
      upregulation of the early growth response1 (Egr1) transcription factor and
      enhanced Id1 expression. Activation of this pathway increases self-renewal
      capacity and resistance to radiation-induced DNA damage, which are dependent on
      Id1. CONCLUSIONS: In GBM, Cox-2-derived PGE2 induces Id1 via EP4-dependent
      activation of MAPK signaling and the Egr1 transcription factor. PGE2-mediated
      induction of Id1 is required for optimal tumor cell self-renewal and radiation
      resistance. Collectively, these findings identify Id1 as a key mediator of PGE2
      dependent modulation of radiation response and lend insight into the mechanisms
      underlying radiation resistance in GBM patients.

PMID- 27022133
TI  - Minireview: Multiomic candidate biomarkers for clinical manifestations of sickle
      cell severity: Early steps to precision medicine.
AB  - In this review, we provide a description of those candidate biomarkers which have
      been demonstrated by multiple-omics approaches to vary in correlation with
      specific clinical manifestations of sickle cell severity. We believe that future
      clinical analyses of severity phenotype will require a multiomic analysis, or an
      omics stack approach, which includes integrated interactomics. It will also
      require the analysis of big data sets. These candidate biomarkers, whether they
      are individual or panels of functionally linked markers, will require future
      validation in large prospective and retrospective clinical studies. Once
      validated, the hope is that informative biomarkers will be used for the
      identification of individuals most likely to experience severe complications, and
      thereby be applied for the design of patient-specific therapeutic approaches and
      response to treatment. This would be the beginning of precision medicine for
      sickle cell disease. 

PMID- 27022134
TI  - Seeding cell approach for tissue-engineered urethral reconstruction in animal
      study: A systematic review and meta-analysis.
AB  - We systematically reviewed published preclinical studies to evaluate the
      effectiveness of cell-seeded tissue engineering approach for urethral
      reconstruction in an animal model. The outcomes were summarized by success
      factors in the animal experiments, which evaluate the possibility and feasibility
      of a clinical application in the future. Preclinical studies of tissue
      engineering approaches for urethral reconstruction were identified through a
      systematic search in PubMed, Embase, and Biosis Previews (web of science SP)
      databases for studies published from 1 January 1980 to 23 November 2014. Primary
      studies were included if urethral reconstruction was performed using a tissue
      engineered biomaterial in any animal species (with the experiment group being a
      cell-seeded scaffold and the control group being a cell-free scaffold) with
      histology and urethrography as the outcome measure. A total of 15 preclinical
      studies were included in our meta-analysis. The histology and urethrography
      outcome between the experimental and control groups were considered to be the
      most clinically relevant. Through this systematic approach, our outcomes
      suggested that applying the cell-seeded biomaterial in creating a neo-urethra was
      stable and effective. And multi-type cells including epithelial cells as well as
      smooth muscle cells or fibroblasts seemed to be a better strategy. Stem cells,
      especially after epithelial differentiation, could be a promising choice for
      future researches.

PMID- 27022135
TI  - Cytotoxicity of atropine to human corneal endothelial cells by inducing
      mitochondrion-dependent apoptosis.
AB  - Atropine, a widely used topical anticholinergic drug, might have adverse effects
      on human corneas in vivo. However, its cytotoxic effect on human corneal
      endothelium (HCE) and its possible mechanisms are unclear. Here, we investigated
      the cytotoxicity of atropine and its underlying cellular and molecular mechanisms
      using an in vitro model of HCE cells and verified the cytotoxicity using cat
      corneal endothelium (CCE) in vivo. Our results showed that atropine at
      concentrations above 0.3125 g/L could induce abnormal morphology and viability
      decline in a dose- and time-dependent manner in vitro. The cytotoxicity of
      atropine was proven by the induced density decrease and abnormality of morphology
      and ultrastructure of CCE cells in vivo. Meanwhile, atropine could also induce
      dose- and time-dependent elevation of plasma membrane permeability, G1 phase
      arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body
      formation of HCE cells. Moreover, 2.5 g/L atropine could also induce caspase-2/
      3/-9 activation, mitochondrial transmembrane potential disruption, downregulation
      of anti-apoptotic Bcl-2 and Bcl-xL, upregulation of pro-apoptotic Bax and Bad,
      and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor. In
      conclusion, atropine above 1/128 of its clinical therapeutic dosage has a dose-
      and time-dependent cytotoxicity to HCE cells in vitro which is confirmed by CCE
      cells in vivo, and its cytotoxicity is achieved by inducing HCE cell apoptosis
      via a death receptor-mediated mitochondrion-dependent signaling pathway. Our
      findings provide new insights into the cytotoxicity and apoptosis-inducing effect
      of atropine which should be used with great caution in eye clinic.

PMID- 27022136
TI  - Immobilized liquid layers: A new approach to anti-adhesion surfaces for medical
      applications.
AB  - Surface fouling and undesired adhesion are nearly ubiquitous problems in the
      medical field, complicating everything from surgeries to routine daily care of
      patients. Recently, the concept of immobilized liquid (IL) interfaces has been
      gaining attention as a highly versatile new approach to antifouling, with a wide
      variety of promising applications in medicine. Here, we review the general
      concepts behind IL layers and discuss the fabrication strategies on medically
      relevant materials developed so far. We also summarize the most important
      findings to date on applications of potential interest to the medical community,
      including the use of these surfaces as anti-thrombogenic and anti-bacterial
      materials, anti-adhesive textiles, high-performance coatings for optics, and as
      unique platforms for diagnostics. Although the full potential and pitfalls of IL
      layers in medicine are just beginning to be explored, we believe that this
      approach to anti-adhesive surfaces will prove broadly useful for medical
      applications in the future.

PMID- 27022137
TI  - The common variant Q192R at the paraoxonase 1 (PON1) gene and its activity are
      responsible for a portion of the altered antioxidant status in type 2 diabetes.
AB  - In this study, we investigated the effects of paraoxonase 1 (PON1) activities and
      the variant PON1-Q192R on the ferric reducing ability of plasma (FRAP) and total
      thiol. In addition, we examined the distribution of genotypes of this variant and
      the relationship of the genotypes with age in patients with type 2 diabetes
      (T2D). A total of 115 patients with T2D were enrolled in this study. Paraoxonase
      activity (PON-para) and arylesterase activity (PON-aryl) were determined using
      spectrophotometric assays. The distribution of the Q192R genotypes was determined
      by the double substrate method. The antioxidant status was evaluated by
      determining FRAP and total thiol. The frequencies of Q and R allozyme were 0.78
      and 0.22, respectively. The multivariate analysis identified a significant
      association between the variables PON1-Q192R (Wilks' lambda = 0.85, P = 0.002)
      and PON-aryl (Wilks' lambda = 0.896, P = 0.017), with FRAP and total thiol. The
      significant difference observed for PON1-Q192R and PON-aryl is primarily due to
      the changes in FRAP levels (eta(2 )= 0.127, P = 0.002 for PON1-Q192R; eta(2 )=
      0.083, P = 0.011 for PON-aryl). The interaction PON1-Q192R-PON-aryl increased the
      effect sizes from 8 to 19% for FRAP. Only in R-carrying genotypes, there were
      significant correlations between both PON-para/HDL (r = -0.574, P < 0.001) and
      PON-aryl/HDL (r = -0.577, P < 0.001) with age. Our data suggest that the variant
      PON1-Q192R and PON1 activity, particularly PON-aryl, influenced the antioxidant
      status in T2D. The interaction of this variant and PON1 activity increased the
      effect size on the antioxidant capacity. Moreover, the presence of the R allozyme
      may potentiate the effects of age on susceptibility to cardiovascular diseases in
      T2D.

PMID- 27022138
TI  - Targeting and therapeutic peptides in nanomedicine for atherosclerosis.
AB  - Peptides in atherosclerosis nanomedicine provide structural, targeting, and
      therapeutic functionality and can assist in overcoming delivery barriers of
      traditional pharmaceuticals. Moreover, their inherent biocompatibility and
      biodegradability make them especially attractive as materials intended for use in
      vivo In this review, an overview of nanoparticle-associated targeting and
      therapeutic peptides for atherosclerosis is provided, including peptides designed
      for cellular targets such as endothelial cells, monocytes, and macrophages as
      well as for plaque components such as collagen and fibrin. An emphasis is placed
      on recent advances in multimodal strategies and a discussion on current
      challenges and barriers for clinical applicability is presented.

PMID- 27022139
TI  - Role of mitochondrial dysfunction in cancer progression.
AB  - Deregulated cellular energetics was one of the cancer hallmarks. Several
      underlying mechanisms of deregulated cellular energetics are associated with
      mitochondrial dysfunction caused by mitochondrial DNA mutations, mitochondrial
      enzyme defects, or altered oncogenes/tumor suppressors. In this review, we
      summarize the current understanding about the role of mitochondrial dysfunction
      in cancer progression. Point mutations and copy number changes are the two most
      common mitochondrial DNA alterations in cancers, and mitochondrial dysfunction
      induced by chemical depletion of mitochondrial DNA or impairment of mitochondrial
      respiratory chain in cancer cells promotes cancer progression to a
      chemoresistance or invasive phenotype. Moreover, defects in mitochondrial
      enzymes, such as succinate dehydrogenase, fumarate hydratase, and isocitrate
      dehydrogenase, are associated with both familial and sporadic forms of cancer.
      Deregulated mitochondrial deacetylase sirtuin 3 might modulate cancer progression
      by regulating cellular metabolism and oxidative stress. These mitochondrial
      defects during oncogenesis and tumor progression activate cytosolic signaling
      pathways that ultimately alter nuclear gene expression, a process called
      retrograde signaling. Changes in the intracellular level of reactive oxygen
      species, Ca(2+), or oncometabolites are important in the mitochondrial retrograde
      signaling for neoplastic transformation and cancer progression. In addition,
      altered oncogenes/tumor suppressors including hypoxia-inducible factor 1 and
      tumor suppressor p53 regulate mitochondrial respiration and cellular metabolism
      by modulating the expression of their target genes. We thus suggest that
      mitochondrial dysfunction plays a critical role in cancer progression and that
      targeting mitochondrial alterations and mitochondrial retrograde signaling might
      be a promising strategy for the development of selective anticancer therapy.

PMID- 27022140
TI  - Rational design of fiber forming supramolecular structures.
AB  - Recent strides in the development of multifunctional synthetic biomimetic
      materials through the self-assembly of multi-domain peptides and proteins over
      the past decade have been realized. Such engineered systems have wide-ranging
      application in bioengineering and medicine. This review focuses on fundamental
      fiber forming alpha-helical coiled-coil peptides, peptide amphiphiles, and
      amyloid-based self-assembling peptides; followed by higher order collagen- and
      elastin-mimetic peptides with an emphasis on chemical / biological
      characterization and biomimicry.

PMID- 27022141
TI  - Original Research: A case-control genome-wide association study identifies
      genetic modifiers of fetal hemoglobin in sickle cell disease.
AB  - Sickle cell disease (SCD) is a group of inherited blood disorders that have in
      common a mutation in the sixth codon of the beta-globin (HBB) gene on chromosome
      11. However, people with the same genetic mutation display a wide range of
      clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic
      modifier of SCD complications leading to milder symptoms and improved long-term
      survival. Therefore, we performed a genome-wide association study (GWAS) using a
      case-control experimental design in 244 African Americans with SCD to discover
      genetic factors associated with HbF expression. The case group consisted of
      subjects with HbF>=8.6% (133 samples) and control group subjects with HbF<=L3.1%
      (111 samples). Our GWAS results replicated SNPs previously identified in an
      erythroid-specific enhancer region located in the second intron of the BCL11A
      gene associated with HbF expression. In addition, we identified SNPs in the
      SPARC, GJC1, EFTUD2 and JAZF1 genes as novel candidates associated with HbF
      levels. To gain insights into mechanisms of globin gene regulation in the HBB
      locus, linkage disequilibrium (LD) and haplotype analyses were conducted. We
      observed strong LD in the low HbF group in contrast to a loss of LD and greater
      number of haplotypes in the high HbF group. A search of known HBB locus
      regulatory elements identified SNPs 5' of delta-globin located in an HbF
      silencing region. In particular, SNP rs4910736 created a binding site for a known
      transcription repressor GFi1 which is a candidate protein for further
      investigation. Another HbF-associated SNP, rs2855122 in the cAMP response element
      upstream of Ggamma-globin, was analyzed for functional relevance. Studies
      performed with siRNA-mediated CREB binding protein (CBP) knockdown in primary
      erythroid cells demonstrated gamma-globin activation and HbF induction,
      supporting a repressor role for CBP. This study identifies possible molecular
      determinants of HbF production.

PMID- 27022142
TI  - Lipidoid nanoparticle mediated silencing of Mcl-1 induces apoptosis in mantle
      cell lymphoma.
AB  - Conventional chemo-immunotherapy fails to cure the majority of mantle cell
      lymphoma patients and causes substantial toxicity. Resistant mantle cell lymphoma
      cells commonly overexpress and are dependent on the anti-apoptotic protein, Mcl
      1, for survival. In this study, we use potent lipidoid nanoparticles to deliver
      siRNA to silence Mcl-1 expression. Studies were conducted using two different
      mantle cell lymphoma cell lines, a normal (JeKo-1) and an aggressive (MAVER-1)
      line, to assess the ability of lipidoid nanoparticles to be used broadly in the
      treatment of mantle cell lymphoma. Mcl-1 mRNA silencing and protein knockdown was
      observed as early as one day after treatment and the lipidoid nanoparticles
      achieved sustained silencing of Mcl-1 mRNA for at least four days in both JeKo-1
      and MAVER-1 cells. Eighty percent silencing was achieved at three days post
      transfection in JeKo-1 cells while 50% silencing was achieved in MAVER-1 cells,
      which are more resistant to transfection. Interestingly, silencing of Mcl-1
      induced apoptosis in nearly 30% of both JeKo-1 and MAVER-1 cells three days post
      transfection. Additionally, Mcl-1 silencing and the resultant apoptosis in mantle
      cell lymphoma cells were dose dependent. These data suggest that lipidoid
      nanoparticles siRNA therapy targeting Mcl-1 has potential as a new treatment
      modality for mantle cell lymphoma and many other cancers that overexpress Mcl-1.
      The combination of anti-Mcl-1 lipidoid nanoparticles with other forms of targeted
      therapy offers hope for reducing or replacing cytotoxic chemotherapy as standard
      treatment for mantle cell lymphoma.

PMID- 27022143
TI  - NFkappaB1 is essential to prevent the development of multiorgan autoimmunity by
      limiting IL-6 production in follicular B cells.
AB  - We examined the role of NFkappaB1 in the homeostasis and function of peripheral
      follicular (Fo) B cells. Aging mice lacking NFkappaB1 (Nfkappab1(-/-)) develop
      lymphoproliferative and multiorgan autoimmune disease attributed in large part to
      the deregulated activity of Nfkappab1(-/-)Fo B cells that produce excessive
      levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced
      germinal center (GC) B cell differentiation, the formation of GC structures was
      severely disrupted in the Nfkappab1(-/-)mice. Bone marrow chimeric mice revealed
      that the Fo B cell-intrinsic loss of NFkappaB1 led to the spontaneous generation
      of GC B cells. This was primarily the result of an increase in IL-6 levels, which
      promotes the differentiation of Fo helper CD4(+)T cells and acts in an autocrine
      manner to reduce antigen receptor and toll-like receptor activation thresholds in
      a population of proliferating IgM(+)Nfkappab1(-/-)Fo B cells. We demonstrate that
      p50-NFkappaB1 represses Il-6 transcription in Fo B cells, with the loss of
      NFkappaB1 also resulting in the uncontrolled RELA-driven transcription of Il
      6.Collectively, our findings identify a previously unrecognized role for
      NFkappaB1 in preventing multiorgan autoimmunity through its negative regulation
      of Il-6 gene expression in Fo B cells.

PMID- 27022144
TI  - Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design.
AB  - Traditionally, vaccines have been developed by cultivating infectious agents and
      isolating the inactivated whole pathogen or some of its purified components. 20
      years ago, reverse vaccinology enabled vaccine discovery and design based on
      information deriving from the sequence of microbial genomes rather than via the
      growth of pathogens. Today, the high throughput discovery of protective human
      antibodies, sequencing of the B cell repertoire, and the increasing structural
      characterization of protective antigens and epitopes provide the molecular and
      mechanistic understanding to drive the discovery of novel vaccines that were
      previously impossible. We are entering a "reverse vaccinology 2.0" era. 

PMID- 27022146
TI  - The Utility of EEG in Attention Deficit Hyperactivity Disorder: A Replication
      Study.
AB  - The routine use of stimulants in pediatrics has increased dramatically over the
      past 3 decades and the long-term consequences have yet to be fully studied. Since
      1978 there have been 7 articles identifying electroencephalogram (EEG)
      abnormalities, particularly epileptiform discharges in children with attention
      deficit hyperactivity disorder (ADHD). Many have studied the prevalence of these
      discharges in this population with varying results. An article published in 2011
      suggests that EEG technology should be considered prior to prescribing stimulants
      to children diagnosed with ADHD due to a high prevalence of epileptiform
      discharges. The 2011 study found a higher prevalence (26%) of epileptiform
      discharges when using 23-hour and sleep-deprived EEGs in comparison with other
      methods of activation (hyperventilation or photostimulation) and conventional
      EEG. We sought to replicate the 2011 results using conventional EEG with the
      added qEEG technologies of automatic spike detection and low-resolution
      electromagnetic tomography analysis (LORETA) brain mapping. Our results showed
      32% prevalence of epileptiform discharges, which suggests that an EEG should be
      considered prior to prescribing stimulant medications.

PMID- 27022145
TI  - Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3
      mRNA.
AB  - Balance in signal transducer and activator of transcription (STAT) activation is
      a key factor in regulating the fate of naive CD4(+)T cells. Here, we demonstrate
      that AT-rich interactive domain-containing protein 5a (Arid5a) in T cells directs
      naive CD4(+)T cells to differentiate into inflammatory CD4(+)T cells, especially
      Th17 cells, through selective stabilization of Stat3(but not Stat1 and Stat5)
      mRNA in an IL-6-dependent manner. Loss of Arid5a in T cells led to reduction of
      STAT3 level under Th17-polarizing conditions, whereas STAT1 and STAT5 in Arid5a
      deficient T cells were highly activated compared with those of WT T cells under
      the same conditions. These cells displayed the feature of antiinflammatory (Il10
      expressing) CD4(+)T cells. Thus, we show a T cell-intrinsic role of Arid5a on
      fate decisions of naive CD4(+)T cells through selective stabilization of Stat3
      mRNA.

PMID- 27022147
TI  - Human Infections by Multiple Spotted Fever Group Rickettsiae in Tennessee.
AB  - Rocky Mountain spotted fever is the most common tick-borne disease in Tennessee.
      However, Rickettsia rickettsii has rarely been isolated from endemic ticks,
      suggesting rickettsioses may be caused by other species. A total of 56 human
      serum samples that were serologically positive for exposure to Rickettsia were
      obtained from commercial laboratories in 2010 and 2011. In addition, 20 paired
      sera from patients with encephalitis and positive Rickettsia serology were
      obtained from the Tennessee Unexplained Encephalitis Surveillance (TUES) study.
      Using an immunofluorescence assay, reactivity of the sera to R. rickettsii,
      Rickettsia montanensis, Rickettsia parkeri, and Rickettsia amblyommii was tested,
      and a comparison of endpoint titers was used to determine the probable antigen
      that stimulated the antibody response. Cross-absorption was conducted for 94.8%
      (N = 91) of the samples due to serologic cross-reactivity. Of the commercial
      laboratory samples, 55.4% (N = 31) had specific reactivity to R. amblyommii and
      44.6% (N = 25) were indeterminate. Of the paired TUES samples, 20% (N = 4) had
      specific reactivity to R. amblyommii, 5% (N = 1) to R. montanensis, and 5% (N =
      1) to R. parkeri Patients with specific reactivity to R. amblyommii experienced
      fever (75%), headache (68%) and myalgia (58%). Rash (36%) and thrombocytopenia
      (40%) were less common. To our knowledge, this is the first time R. amblyommii
      has been reported as a possible causative agent of rickettsioses in Tennessee.

PMID- 27022148
TI  - Challenges to Arboviral Surveillance in Tennessee: Health-Care Providers'
      Attitudes and Behaviors.
AB  - Surveillance of arboviruses depends on health-care providers' ability to diagnose
      and report human cases of disease. The purposes of this study were to assess
      Tennessee providers' 1) self-efficacy toward diagnosis and management, 2)
      clinical practices, and 3) variation in these measures by provider
      characteristics. A survey was e-mailed to 13,851 providers, of which 916 (7%)
      responded. Respondents diagnosed more arboviruses in the previous year than were
      recorded in surveillance records, an indication of underreporting. Respondents
      had low to moderate self-efficacy toward diagnosis and management of arboviruses.
      Although more than 70% (N = 589) used paired serology, only 46% (N = 396) asked
      patients to return for a convalescent specimen draw within the correct time
      frame. One of the most commonly reported barriers to testing was uncertainty
      about which tests to order. Providers working in family medicine and urgent care,
      nurse practitioners, and those at outpatient facilities had lower rates of high
      self-efficacy than their counterparts working in other settings and from other
      specialties. Clinical practices were influenced by specialty, designation,
      setting, and geography but not by years of experience. Education to improve
      arboviral surveillance in Tennessee is warranted. Topics could include proper
      diagnosis and management, appropriate testing and overcoming barriers to testing,
      and public health reporting.

PMID- 27022149
TI  - Socioeconomic and Ecological Factors Influencing Aedes aegypti Prevalence,
      Abundance, and Distribution in Dhaka, Bangladesh.
AB  - This study examined household risk factors and prevalence, abundance, and
      distribution of immature Aedes aegypti and Aedes albopictus, and their
      association with socioeconomic and ecological factors at urban zonal and
      household levels in the city of Dhaka, Bangladesh. During the 2011 monsoon, 826
      households in 12 randomly selected administrative wards were surveyed for vector
      mosquitoes. Results revealed that the abundance and distribution of immature Ae.
      aegypti and Ae. albopictus, and pupae-per-person indices did not vary
      significantly among the zones with varied socioeconomic status. Of 35 different
      types of identified wet containers, 30 were infested, and among the 23 pupae
      positive container types, nine were defined as the "most productive" for pupae
      including: disposable plastic containers (12.2% of 550), sealable plastic barrels
      (12.0%), tires (10.4%), abandoned plastic buckets (9.6%), flower tub and trays
      (8.5%), refrigerator trays (6.5%), plastic bottles (6.4%), clay pots (4.9%), and
      water tanks (1.6%). When the function of the containers was assessed, ornamental,
      discarded, and household repairing and reconstruction-related container
      categories were found significantly associated with the number of pupae in the
      households. The purpose of storing water and income variables were significant
      predictors of possession of containers that were infested by vector mosquitoes.

PMID- 27022150
TI  - Assessing Perceived Challenges to Laboratory Testing at a Malawian Referral
      Hospital.
AB  - Adequate laboratory infrastructure in sub-Saharan Africa is vital for tackling
      the burden of infectious diseases such as human immunodeficiency virus and
      acquired immune deficiency syndrome, malaria, and tuberculosis, yet laboratories
      are ill-integrated into the diagnostic and care delivery process in low-resource
      settings. Although much of the literature focuses on disease-specific challenges
      around laboratory testing, we sought to identify horizontal challenges to the
      laboratory testing process through interviews with clinicians involved in the
      diagnostic process. Based on 22 interviews with physicians, nurses, clinical
      officers, medical students, and laboratory technicians, technologists and
      supervisors, we identified 12 distinct challenges in the areas of staff,
      materials, workflow, and the blood bank. These challenges underscore the
      informational challenges that compound more visible resource shortages in the
      laboratory testing process, which lend themselves to horizontal strengthening
      efforts around the diagnostic process.

PMID- 27022151
TI  - Forty Years of Dengue Surveillance at a Tertiary Pediatric Hospital in Bangkok,
      Thailand, 1973-2012.
AB  - Long-term observational studies can provide valuable insights into overall dengue
      epidemiology. Here, we present analysis of dengue cases at a pediatric hospital
      in Bangkok, Thailand, during a 40-year period from 1973 to 2012. Data were
      analyzed from 25,715 hospitalized patients with laboratory-confirmed dengue virus
      (DENV) infection. Several long-term trends in dengue disease were identified
      including an increase in mean age of hospitalized cases from an average of 7-8
      years, an increase after 1990 in the proportion of post-primary cases for DENV-1
      and DENV-3, and a decrease in the proportion of dengue hemorrhagic fever and
      dengue shock syndrome cases in primary and post-primary cases over time.
      Exploratory mechanistic analysis of these observed trends considered changes in
      diagnostic methods, demography, force of infection, and Japanese encephalitis
      vaccination as possible explanations. Thailand is an important setting for
      studying DENV transmission as it has a "mature" dengue epidemiology with a strong
      surveillance system in place since the early 1970s. We characterized changes in
      dengue epidemiology over four decades, and possible impact of demographic and
      other changes in the human population. These results may inform other countries
      where similar changes in transmission and population demographics may now or may
      soon be occurring.

PMID- 27022152
TI  - Epidemiology of Guillain-Barre Syndrome in Aruba.
AB  - The epidemiology of Guillain-Barre syndrome (GBS) in tropical areas is different
      compared with developed countries. We investigated the epidemiology of GBS on the
      Caribbean island of Aruba. Data were collected retrospectively from all 36
      patients hospitalized with GBS between 2003 and 2011 in Aruba. We observed a
      seasonal distribution of GBS cases with a peak in February. The incidence rate
      (IR) fluctuated heavily between individual years. The overall IR was
      3.93/100,000, which is higher than that observed in developed countries.
      Serological studies indicated a possible relation of GBS cases with dengue virus
      infections. We also observed a relation between the annual number of dengue cases
      in Aruba and the number of GBS cases in the same year. We conclude that the
      epidemiology of GBS in tropical areas can be different from temperate climate
      regions and that dengue may be a trigger for developing GBS.

PMID- 27022153
TI  - Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue
      Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.
AB  - We evaluated the safety and immunogenicity of two doses of a live-attenuated,
      tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a
      dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were
      followed for 1 year after dose 2 and then given a booster dose (F17/Pre
      formulation), and followed for four more years (Child study). In the Infant
      study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5
      years after dose 2 and then given a booster dose (F17) and followed for one
      additional year. Two clinically notable events were observed, both in dengue
      vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years
      after dose 2 and 1 case of suspected dengue after booster vaccinations. The
      booster vaccinations had a favorable safety profile in terms of reactogenicity
      and adverse events reported during the 1-month follow-up periods. No vaccine
      related serious adverse events were reported during the studies. Neutralizing
      antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting,
      which elicited a short-lived booster response but did not provide a long-lived,
      multivalent antibody response in most subjects. Overall, this candidate vaccine
      did not elicit a durable humoral immune response.

PMID- 27022154
TI  - Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan:
      Insights into Toxicity and Antivenom Neutralization.
AB  - Geographical variations of snake venoms can result in suboptimal effectiveness of
      Indian antivenoms that are currently used in most South Asian countries. This
      study investigated the toxicity and neutralization profile of the venom and
      toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent
      antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand),
      and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase
      high-performance liquid chromatography fractionations followed by toxin
      identification through liquid chromatography-mass spectrometry (MS)/MS indicated
      that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long
      neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs)
      (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in
      neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its
      LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N.
      kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg
      toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All
      the three antivenoms were weak in neutralizing the SNTX (potency = 0.03-0.04 mg
      toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra
      venom. In a challenge-rescue experiment, envenomed mice were prevented from death
      by a maximal dose of VPAV (intravenous 200 MUL) but the recovery from paralysis
      was slow, indicating the need for higher or repeated doses of VPAV. Our results
      suggest that optimal neutralization for Pakistani N. naja venom may be achieved
      by improving the formulation of antivenom production to enhance antivenom
      immunoreactivity against long and SNTXs.

PMID- 27022155
TI  - Characterization of a Novel Murine Model to Study Zika Virus.
AB  - The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing
      outbreak of febrile illness across the Americas. ZIKV was previously thought to
      cause only a mild, flu-like illness, but during the current outbreak, an
      association with Guillain-Barre syndrome and microcephaly in neonates has been
      detected. A previous study showed that ZIKV requires murine adaptation to
      generate reproducible murine disease. In our study, a low-passage Cambodian
      isolate caused disease and mortality in mice lacking the interferon (IFN) alpha
      receptor (A129 mice) in an age-dependent manner, but not in similarly aged
      immunocompetent mice. In A129 mice, viremia peaked at ~10(7) plaque-forming
      units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day
      1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic
      disease, including tremors, by day 6. Robust replication was also noted in the
      testis. In this model, all mice infected at the youngest age (3 weeks) succumbed
      to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia,
      and weight loss but recovered starting on day 8. In addition, AG129 mice, which
      lack both type I and II IFN responses, supported similar infection kinetics to
      A129 mice, but with exaggerated disease signs. This characterization of an Asian
      lineage ZIKV strain in a murine model, and one of the few studies reporting a
      model of Zika disease and demonstrating age-dependent morbidity and mortality,
      could provide a platform for testing the efficacy of antivirals and vaccines.

PMID- 27022156
TI  - Application of Serological Tools and Spatial Analysis to Investigate Malaria
      Transmission Dynamics in Highland Areas of Southwest Uganda.
AB  - Serological markers, combined with spatial analysis, offer a comparatively more
      sensitive means by which to measure and detect foci of malaria transmission in
      highland areas than traditional malariometric indicators. Plasmodium falciparum
      parasite prevalence, seroprevalence, and seroconversion rate to P. falciparum
      merozoite surface protein-119 (MSP-119) were measured in a cross-sectional survey
      to determine differences in transmission between altitudinal strata. Clusters of
      P. falciparum parasite prevalence and high antibody responses to MSP-119 were
      detected and compared. Results show that P. falciparum prevalence and
      seroprevalence generally decreased with increasing altitude. However,
      transmission was heterogeneous with hotspots of prevalence and/or seroprevalence
      detected in both highland and highland fringe altitudes, including a serological
      hotspot at 2,200 m. Results demonstrate that seroprevalence can be used as an
      additional tool to identify hotspots of malaria transmission that might be
      difficult to detect using traditional cross-sectional parasite surveys or through
      vector studies. Our study findings identify ways in which malaria prevention and
      control can be more effectively targeted in highland or low transmission areas
      via serological measures. These tools will become increasingly important for
      countries with an elimination agenda and/or where malaria transmission is
      becoming patchy and focal, but receptivity to malaria transmission remains high.

PMID- 27022157
TI  - Centralizing content and distributing labor: a community model for curating the
      very long tail of microbial genomes.
AB  - The last 20 years of advancement in sequencing technologies have led to
      sequencing thousands of microbial genomes, creating mountains of genetic data.
      While efficiency in generating the data improves almost daily, applying
      meaningful relationships between taxonomic and genetic entities on this scale
      requires a structured and integrative approach. Currently, knowledge is
      distributed across a fragmented landscape of resources from government-funded
      institutions such as National Center for Biotechnology Information (NCBI) and
      UniProt to topic-focused databases like the ODB3 database of prokaryotic operons,
      to the supplemental table of a primary publication. A major drawback to large
      scale, expert-curated databases is the expense of maintaining and extending them
      over time. No entity apart from a major institution with stable long-term funding
      can consider this, and their scope is limited considering the magnitude of
      microbial data being generated daily. Wikidata is an openly editable, semantic
      web compatible framework for knowledge representation. It is a project of the
      Wikimedia Foundation and offers knowledge integration capabilities ideally suited
      to the challenge of representing the exploding body of information about
      microbial genomics. We are developing a microbial specific data model, based on
      Wikidata's semantic web compatibility, which represents bacterial species,
      strains and the gene and gene products that define them. Currently, we have
      loaded 43,694 gene and 37,966 protein items for 21 species of bacteria, including
      the human pathogenic bacteriaChlamydia trachomatis.Using this pathogen as an
      example, we explore complex interactions between the pathogen, its host,
      associated genes, other microbes, disease and drugs using the Wikidata SPARQL
      endpoint. In our next phase of development, we will add another 99 bacterial
      genomes and their gene and gene products, totaling ~900,000 additional entities.
      This aggregation of knowledge will be a platform for community-driven
      collaboration, allowing the networking of microbial genetic data through the
      sharing of knowledge by both the data and domain expert.

PMID- 27022158
TI  - RSIADB, a collective resource for genome and transcriptome analyses in
      Rhizoctonia solani AG1 IA.
AB  - Rice [Oryza sativa (L.)] feeds more than half of the world's population.
      Rhizoctonia solaniis a major fungal pathogen of rice causing extreme crop losses
      in all rice-growing regions of the world. R. solani AG1 IA is a major cause of
      sheath blight in rice. In this study, we constructed a comprehensive and user
      friendly web-based database, RSIADB, to analyse its draft genome and
      transcriptome. The database was built using the genome sequence (10,489 genes)
      and annotation information for R. solani AG1 IA. A total of six RNAseq samples of
      R. solani AG1 IA were also analysed, corresponding to 10, 18, 24, 32, 48 and 72 h
      after infection of rice leaves. The RSIADB database enables users to search,
      browse, and download gene sequences for R. solani AG1 IA, and mine the data using
      BLAST, Sequence Extractor, Browse and Construction Diagram tools that were
      integrated into the database. RSIADB is an important genomic resource for
      scientists working with R. solani AG1 IA and will assist researchers in analysing
      the annotated genome and transcriptome of this pathogen. This resource will
      facilitate studies on gene function, pathogenesis factors and secreted proteins,
      as well as provide an avenue for comparative analyses of genes expressed during
      different stages of infection. Database
      URL:http://genedenovoweb.ticp.net:81/rsia/index.php.

PMID- 27022159
TI  - myPhyloDB: a local web server for the storage and analysis of metagenomic data.
AB  - myPhyloDB v.1.1.2 is a user-friendly personal database with a browser-interface
      designed to facilitate the storage, processing, analysis, and distribution of
      microbial community populations (e.g. 16S metagenomics data). MyPhyloDB archives
      raw sequencing files, and allows for easy selection of project(s)/sample(s) of
      any combination from all available data in the database. The data processing
      capabilities of myPhyloDB are also flexible enough to allow the upload and
      storage of pre-processed data, or use the built-in Mothur pipeline to automate
      the processing of raw sequencing data. myPhyloDB provides several analytical
      (e.g. analysis of covariance,t-tests, linear regression, differential abundance
      (DESeq2), and principal coordinates analysis (PCoA)) and normalization
      (rarefaction, DESeq2, and proportion) tools for the comparative analysis of
      taxonomic abundance, species richness and species diversity for projects of
      various types (e.g. human-associated, human gut microbiome, air, soil, and water)
      for any taxonomic level(s) desired. Finally, since myPhyloDB is a local web
      server, users can quickly distribute data between colleagues and end-users by
      simply granting others access to their personal myPhyloDB database. myPhyloDB is
      available athttp://www.ars.usda.gov/services/software/download.htm?softwareid=472
      and more information along with tutorials can be found on our
      websitehttp://www.myphylodb.org. Database URL:http://www.myphylodb.org.

PMID- 27022160
TI  - CoDNaS 2.0: a comprehensive database of protein conformational diversity in the
      native state.
AB  - CoDNaS (conformational diversity of the native state) is a protein conformational
      diversity database. Conformational diversity describes structural differences
      between conformers that define the native state of proteins. It is a key concept
      to understand protein function and biological processes related to protein
      functions. CoDNaS offers a well curated database that is experimentally driven,
      thoroughly linked, and annotated. CoDNaS facilitates the extraction of key
      information on small structural differences based on protein movements. CoDNaS
      enables users to easily relate the degree of conformational diversity with
      physical, chemical and biological properties derived from experiments on protein
      structure and biological characteristics. The new version of CoDNaS includes ~70%
      of all available protein structures, and new tools have been added that run
      sequence searches, display structural flexibility profiles and allow users to
      browse the database for different structural classes. These tools facilitate the
      exploration of protein conformational diversity and its role in protein function.
      Database URL:http://ufq.unq.edu.ar/codnas.

PMID- 27022161
TI  - Long-Term Outcome of Patients with Ulcerative Colitis and Primary Non-response to
      Infliximab.
AB  - BACKGROUND AND AIMS: We studied the long-term outcome of patients with ulcerative
      colitis [UC] and primary non response [PNR] to infliximab and searched for
      predictors of colectomy in these patients. METHODS: This retrospective, multi
      centre study included UC patients from three European referral centres, with PNR
      to infliximab defined as a lack of clinical improvement after the induction
      therapy, leading to drug discontinuation. Relapse, for patients who continued on
      biologicals after PNR to infliximab, was defined as drug discontinuation for PNR,
      loss of response, or serious adverse event. Serum infliximab concentrations at
      Weeks 2 and 6 were evaluated using an enzyme-linked immunosorbent assay [ELISA]
      developed in house. RESULTS: The study population consisted of 99 anti-tumour
      necrosis factor [TNF]-naive patients with UC and PNR to infliximab. At the end of
      follow-up (median: 3.2 [interquartile range 1-6.3] years), 55 [55.6%] of these
      patients underwent colectomy. Multiple Cox regression analysis identified acute
      severe UC (hazard ratio [HR]: 24; 95% confidence interval [CI]: 2.5-231; p =
      0.006], baseline C-reactive protein [CRP] > 5mg/l [HR: 11; 95% CI: 2.1-58.8; p =
      0.005], baseline albumin < 40g/l [HR: 9.5; 95% CI: 1.3-71.4; p = 0.026], and
      infliximab concentration at Week 2 < 16.5 MUg/ml [HR: 5.6; 95% CI: 1.1-27.8; p =
      0.034] as independent predictors of colectomy. Regarding patients who continued
      on biologicals after PNR to infliximab, there was a marginally higher cumulative
      probability for relapse in patients switching to another anti-TNF agent compared
      with those swapping to vedolizumab [p logrank = 0.08]. CONCLUSIONS: About half of
      UC patients with PNR to infliximab will undergo colectomy. Patients with severe
      inflammation and low serum infliximab concetrations during the induction phase
      are at greatest risk.

PMID- 27022162
TI  - Endoplasmic reticulum stress up-regulates Nedd4-2 to induce autophagy.
AB  - The accumulation of unfolded proteins within the endoplasmic reticulum (ER)
      causes ER stress and activation of unfolded protein response (UPR). This response
      can trigger ER-associated degradation and autophagy, which clear unfolded
      proteins and restore protein homeostasis. Recently, it has become clear that
      ubiquitination plays an important role in the regulation of autophagy. In the
      present study, we investigated how the E3 ubiquitin ligase neural precursor cell
      expressed, developmentally down-regulated protein 4-2 (Nedd4-2) interacts with ER
      stress and autophagy. In mice, we found that an increase in the expression of
      Nedd4-2, which was concomitant with the activation of the UPR and autophagy, was
      caused by a prolonged high-fructose and high-fat diet that induces ER stress in
      the liver. Pharmacologic induction of ER stress also led to an increase in Nedd4
      2 expression in cultured cells, which was coincident with UPR and autophagy
      activation. The inhibition of inositol-requiring enzyme 1 significantly
      suppressed Nedd4-2 expression. Moreover, increased Nedd4-2 expression in vivo was
      closely associated with the activation of inositol-requiring enzyme 1 and
      increased expression of the spliced form of X-box binding protein 1. Furthermore,
      knockdown of Nedd4-2 in cultured cells suppressed both basal autophagy and ER
      stress-induced autophagy, whereas overexpression of Nedd4-2-induced autophagy.
      Taken together, our findings provide evidence that Nedd4-2 is up-regulated in
      response to ER stress by the spliced form of X-box binding protein 1 and that
      this is important in the induction of an appropriate autophagic response.-Wang,
      H. Sun, R.-Q., Camera, D., Zeng, X.-Y., Jo, E., Chan, S. M. H., Herbert, T. P.,
      Molero, J. C., Ye, J.-M. Endoplasmic reticulum stress up-regulates Nedd4-2 to
      induce autophagy.

PMID- 27022163
TI  - Could edaravone prevent gentamicin ototoxicity? An experimental study.
AB  - OBJECTIVES: Clinical application of gentamicin may cause nephrotoxicity and
      ototoxicity. Our study is the first study to investigate the protective effects
      of edaravone against the gentamicin-induced ototoxicity. We investigated the
      protective effect of intraperitoneal (i.p.) edaravone application against
      gentamicin-induced ototoxicity in guinea pigs. METHODS: Fourteen guinea pigs were
      divided into two equal groups consisting of a control group and a study group.
      One-hundred sixty milligrams per kilogram subcutaneous gentamicin and 0.3 mL i.p.
      saline were applied simultaneously once daily to seven guinea pigs in the control
      group (group 1). One-hundred sixty milligrams per kilogram gentamicin was applied
      subcutaneously and 3 mg/kg edaravone was applied intraperitoneally once daily for
      7 days simultaneously to seven guinea pigs in the study group (group 2).
      Following the drug application, auditory brainstem response measurements were
      performed for the left ear on the 3rd and 7th days. RESULTS: Hearing threshold
      values of the group 1 and group 2 measured in the 3rd day of the study were
      detected as 57.14 +/- 4.88 and 82.86 +/- 7.56, respectively. This difference was
      statistically significant ( p < 0.05). Hearing threshold values of the group 1
      and group 2 measured in the 7th day of the study were detected as 87.14 +/- 4.88
      and 62.86 +/- 4.88, respectively. This difference was statistically significant (
      p < 0.05). CONCLUSION: A statistically significant difference between the average
      threshold values of edaravone-administered group 2 and that of group 1 without
      edaravone was found. These differences show that systemic edaravone
      administration could diminish ototoxic effects of gentamicin and the severity of
      the hearing loss.

PMID- 27022164
TI  - The mastery of antidotes: A survey of antidote knowledge and availability among
      emergency physicians in registered hospitals in China.
AB  - AIM: To describe various types of Chinese hospitals' emergency department (ED)
      physicians' knowledge of antidotes and the comparative availability of
      toxicological treatments at these hospitals. METHODS: We emailed a written survey
      to the ED doctors of 900 hospitals in China. The hospitals' names and addresses
      were obtained and randomly selected from the 6214 hospitals registered by the
      Chinese Medical Association. The survey included 23 questions on antidotes to
      commonly seen poisonings as well as questions on the availability of antidotes
      and decontamination techniques at each hospital. RESULTS: Six hundred and fifty
      three hospital emergency directors responded to the survey 72.6% response rate).
      Overall knowledge of antidotes is not high and varied depending on antidote.
      Physicians in Eastern China, those working in tertiary-level hospitals and those
      working in hospitals with higher numbers of beds performed significantly better.
      On average, only 35.6% of the 23 antidotes were available in all reporting
      hospitals; 54.1% can get these antidotes from nearby hospitals and 42.0% can get
      them from a local CDC poison control center. However, only 57.3% can get a
      requested antidote within two hours. Gastric lavage is the most widely used
      decontamination procedure, and the availability of extracorporeal decontamination
      techniques is between 67.2% and 79.6% (depending on type). CONCLUSION: Knowledge
      of specific antidotes correlated significantly with size, type, and region of
      hospital in China rather than with individual physician characteristics.
      Significant antidotes remain unavailable or unavailable within 2 h in about half
      of all hospitals surveyed, although all major acute decontamination treatments
      and techniques seem quite prevalent.

PMID- 27022165
TI  - Quantitative determination of methamphetamine in oral fluid by liquid-liquid
      extraction and gas chromatography/mass spectrometry.
AB  - Methamphetamine abuse is one of the most medical and social problems many
      countries face. In spite of the ban on the use of methamphetamine, it is widely
      available in Iran's drug black market. There are many analytical methods for the
      detection of methamphetamine in biological specimen. Oral fluid has become a
      popular specimen to test for the presence of methamphetamine. The purpose of the
      present study was to develop a method for the extraction and detection of
      methamphetamine in oral fluid samples using liquid-liquid extraction (LLE) and
      gas chromatography/mass spectrometry (GC/MS) methods. An analytical study was
      designed in that blank and 50 authentic oral fluid samples were collected to be
      first extracted by LLE and subsequently analysed by GC/MS. The method was fully
      validated and showed an excellent intra- and inter-assay precision (reflex
      sympathetic dystrophy ? 10%) for external quality control samples. Recovery with
      LLE methods was 96%. Limit of detection and limit of quantitation were 5 and 15
      ng/mL, respectively. The method showed high selectivity, no additional peak due
      to interfering substances in samples was observed. The introduced method was
      sensitive, accurate and precise enough for the extraction of methamphetamine from
      oral fluid samples in forensic toxicology laboratories.

PMID- 27022166
TI  - Exposure to triptolide affects follicle development in NIH mice: Role of
      endoplasmic reticulum stress in granulosa cell apoptosis.
AB  - Triptolide (TPL) is a main active compound isolated from Tripterygium wilfordii
      Hook f. Despite its positive therapeutic effect, the female reproductive toxicity
      of TPL is still the bottleneck of clinical application. The study was designed to
      investigate the adverse effects on mice ovary and underlying mechanism of TPL.
      Adult female NIH mice were treated with two therapeutic doses of TPL (25 and 50
      MUg/kg/d) for 50 days, respectively. Mice estrous cycle was detected by vaginal
      cytology method. Half mice from each group were selected randomly to perform
      superovulation. Quality and quantity of ovulated eggs were evaluated. Other mice
      from each group were executed for morphological study. Ovarian histological
      sections were stained by H&E staining for ovarian pathologic detection and
      follicular counts. Apoptotic granulosa cell (GC) was detected by terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Endoplasmic
      reticulum (ER) stress-related proteins and antiapoptotic X-linked inhibitor of
      apoptosis protein (XIAP) were detected by immunohistochemical method. Two doses
      of TPL resulted in estrous cycle disorder and follicles in development reservoir
      impairment. Quality and quantity of mice ovulated eggs significantly decreased
      after TPL treatment. Ovarian pathologic examination revealed TPL-induced TUNEL
      positive GCs increase and ER stress-related proteins (78-kDa glucose-regulated
      protein, p-protein kinase-like endoplasmic reticulum kinase, p-eukaryotic
      initiation factor 2alpha, and CCAAT/enhancer binding protein homologous protein)
      expression upregulation. Meanwhile, the expression of antiapoptosis protein XIAP
      in mice ovary was obviously inhibited by TPL. Our results may demonstrate that
      therapeutic doses of TPL can injure ovary function, but there is no difference
      between high-dose and low-dose groups. GCs apoptosis by ER stress pathway and
      antiapoptotic function impairment may partly mediate TPL-induced ovary toxicity.

PMID- 27022167
TI  - Vestibular end organ injury induced by middle ear treatment with ferric chloride
      in rats.
AB  - Sensorineural hearing loss, ataxia, pyramidal signs, and vestibular deficits
      characterize superficial siderosis of the central nervous system. This study
      investigated changes in vestibular function, free radical formation, and
      phosphorylated cJun expression in the vestibular end organs after middle ear
      treatment with a ferric chloride (FeCl3) solution. A single injection of 70%
      FeCl3 solution into the unilateral middle ear cavity caused static vestibular
      symptoms, such as spontaneous nystagmus and head tilt. Asymmetric expression of c
      Fos protein was observed in the bilateral vestibular nuclei and prepositus
      hypoglossal nuclei within 6 h after injection. Histopathologic examinations
      revealed partial hair cell loss, degeneration of the supporting stroma, and
      terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in
      the neuroepithelial layer of the crista ampullaris in FeCl3-treated animals. 5
      (And-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester and
      diaminofluorescein-2 diacetate fluorescence and immunoreactivity for
      nitrotyrosine increased markedly in the sensory neuroepithelial layer and nerve
      bundles of the crista ampullaris after 2 h. Strong immunoreactivity for phospho
      cJun and cJun was observed in the type I hair cells of the crista ampullaris 120
      h after injection. Thus, a single short-term treatment with a high concentration
      of FeCl3 in the unilateral middle ear cavity can induce activation of
      intracellular signals for cJun protein and oxidative stress through the formation
      of reactive oxygen species and nitric oxide in vestibular sensory receptors,
      resulting in vestibular dysfunction. These results suggest that activation of
      intracellular signals for cJun protein and oxidative stress may be a key
      component of the pathogenesis of vestibular deficits in patients with superficial
      siderosis.

PMID- 27022168
TI  - Virtual Touch Tissue Imaging for Differential Diagnosis of Thyroid Nodules:
      Additional Value of the Area Ratio.
AB  - OBJECTIVES: To evaluate the additional value of the area ratio on Virtual Touch
      tissue imaging (VTI; Siemens Medical Solutions, Mountain View, CA) for diagnosis
      of thyroid nodules referred to surgery. METHODS: From April 2013 to February
      2014, 205 consecutive patients with 225 histologically proven thyroid nodules
      were enrolled in this retrospective study. Virtual Touch tissue imaging and area
      ratio measurements were performed for each nodule. The area ratio was defined as
      the area of the nodule on VTI divided by the area on B-mode sonography. Nodule
      stiffness on VTI was graded from I (soft) to VI (hard). Receiver operating
      characteristic curve analyses of VTI, area ratio, and the combination of VTI and
      area ratio were performed. The sensitivity, specificity, accuracy, positive
      predictive value (PPV), negative predictive value (NPV), and Youden index were
      also evaluated. RESULTS: By receiver operating characteristic curve analyses, the
      cutoff values were VTI grade IV and area ratio of 1.09, respectively. Nodules
      with VTI grade IV or higher or area ratio of 1.09 or higher were more likely to
      be malignant. The sensitivity, specificity, accuracy, PPV, NPV, and Youden index
      were 78.6%, 92.3%, 88.0%, 82.1%, 90.5%, and 0.709 for VTI and 81.4%, 87.1%,
      85.3%, 74.0%, 91.2%, and 0.685 for area ratio (all P > .05). However, when using
      the criterion of VTI grade IV or higher and area ratio of 1.09 or higher as a
      combination, the sensitivity, specificity, accuracy, PPV, NPV, and Youden index
      increased to 94.3%, 97.4%, 96.4%, 94.3%, 97.4%, and 0.917 (all P< .05 compared to
      VTI or area ratio alone, except for specificity between VTI and the combination).
      CONCLUSIONS: The diagnostic performance of VTI grading and the area ratio for
      differentiation between benign and malignant thyroid nodules is equivalent. The
      performance is further improved with a combination of VTI grading and area ratio
      analysis.

PMID- 27022169
TI  - Factors Influencing the Outcome of Ultrasound-Guided Fine-Needle Aspiration for
      Salivary Gland Lesion Diagnosis.
AB  - OBJECTIVES: This study aimed to assess multiple factors influencing the outcomes
      of ultrasound (US)-guided fine-needle aspiration (FNA) of salivary gland lesions.
      METHODS: From 2008 to 2013, a single radiologist performed US-guided FNA of
      salivary gland lesions in 243 patients. With the exclusion of pure cysts, poor
      image quality, and insufficient static image cases, 218 salivary gland lesions in
      218 patients were included. The composition, size, location, and vascularity of
      the lesions were retrospectively investigated on the basis of sonographic
      findings by the same radiologist. The relationship between sampling adequacy and
      multiple factors was compared, and the diagnostic accuracy of US-guided FNA of
      salivary gland lesions was calculated by using the final diagnosis as a reference
      standard. RESULTS: The sampling adequacy rate for US-guided FNA of the 218
      salivary gland lesions was 96.8% (211 of 218). A significant difference was
      observed in the composition and vascularity of the lesions (P < .0001), whereas
      there was no significant difference in the patient age and sex, lesion size,
      lesion location, and needle size. The rate of inadequate sampling increased in
      predominantly cystic lesions compared with solid lesions as well as in low
      vascularity lesions compared with high-vascularity lesions. Of the 218 lesions,
      178 (81.7%) were ultimately diagnosed, and most were benign (162 of 178 [91.0%]).
      When 3 cases with indeterminate cytologic results were excluded, the sensitivity,
      specificity, positive and negative predictive values, and accuracy of US-guided
      FNA of salivary gland lesions were 64.3%, 98.8%, 81.8%, 97.0%, and 96.0%,
      respectively. CONCLUSIONS: When using US-guided FNA to diagnose salivary gland
      lesions, sampling adequacy depends on the composition or vascularity of the
      lesions.

PMID- 27022170
TI  - Three-Dimensional Transvaginal Sonography and Magnetic Resonance Imaging for
      Local Staging of Cervical Cancer: An Agreement Study.
AB  - OBJECTIVES: To evaluate the agreement of clinical examination, 2-dimensional (2D)
      sonography, and 3-dimensional (3D) sonography with magnetic resonance imaging
      (MRI) for local staging of cervical cancer. METHODS: We conducted a prospective
      study including women with a diagnosis of carcinoma of the cervix. All women were
      staged clinically and underwent 2D and 3D transvaginal sonography and MRI before
      treatment for assessing tumor size and parametrial, bladder, and rectal
      involvement using the examiner's subjective impression. Agreement between
      sonography and MRI was assessed by calculating the kappa index and percentage of
      agreement. RESULTS: Forty women were included (mean age +/- SD, 46.6 +/- 11.4
      years). Eleven had early-stage (IA and IB1) disease, and 29 had advanced-stage
      (IB2-IVB) disease. A significant correlation for tumor size estimation was found
      between MRI and pelvic examination (r = 0.754; P < .001), MRI and 2D sonography
      (r = 0.649; P < .001), and MRI and 3D sonography (r = 0.657; P< .001). Agreement
      for parametrial infiltration between MRI and pelvic examination was fair (kappa =
      0.26; 95% confidence interval [CI], 0.10-0.54; 62.5% agreement), between MRI and
      2D sonography was moderate (kappa = 0.41; 95% CI, 0.15-0.66; 70.0% agreement),
      and between MRI and 3D sonography was good (kappa = 0.60; 95% CI, 0.35-0.85;
      80.0% agreement). Agreement for bladder involvement between MRI and pelvic
      examination was moderate (kappa = 0.48; 95% CI, 0.10-0.99; 95.0% agreement),
      between MRI and 2D sonography was moderate (kappa = 0.48; 95% CI, 0.10-0.99;
      95.0% agreement), and between MRI and 3D sonography was very good (kappa = 0.84;
      95% CI, 0.55-1.0; 97.5% agreement). Agreement for rectal involvement was not
      calculated because of the very small number of cases. CONCLUSIONS: Three
      dimensional sonography showed good agreement with MRI for assessing parametrial
      infiltration and bladder involvement in cervical cancer.

PMID- 27022171
TI  - Elastographic Strain Index in the Evaluation of Focal Lesions Detected With
      Transrectal Sonography of the Prostate Gland.
AB  - OBJECTIVES: The purpose of this study was to evaluate the value of elastography
      in evaluating focal lesions detected by transrectal sonography and to suggest a
      reference strain index. METHODS: Sixty-nine patients with focal lesions on
      transrectal sonography were referred to our department for prostate biopsy. Focal
      lesions were classified as either highly or less suspicious lesions by our
      criteria. A strain index from elastography was calculated for the focal lesions.
      Systematic 12-core randomized biopsies plus 2 targeted biopsies were performed.
      The mean strain indices for malignant and benign focal lesions were compared, and
      a cutoff strain index was attained to maximize the sensitivity and specificity
      for prostate cancer. Strain indices were correlated with Gleason scores. RESULTS:
      The mean strain index +/- SD for malignant focal lesions (3.26 +/- 1.77) was
      significantly higher than that for benign focal lesions (2.16 +/- 1.52; P =
      .008). The sensitivity, specificity, and area under the receiver operating
      characteristic curve for diagnosing cancer were 66.7%, 71.1%, and 0.701,
      respectively, at a strain index cutoff value of greater than 2.4. The strain
      index showed a moderate linear correlation with the Gleason score (r = 0.441; P =
      .013). CONCLUSIONS: Any focal lesion on transrectal sonography with a strain
      index of greater than 2.4 is at risk for prostate cancer.

PMID- 27022172
TI  - Prenatal and Postnatal Survival of Fetal Tetralogy of Fallot: A Meta-analysis of
      Perinatal Outcomes and Associated Genetic Disorders.
AB  - OBJECTIVES: The aim of this systematic review was to compare the postnatal
      outcomes, genetic testing results, and sonographic findings in 3 subtypes of
      tetralogy of Fallot. METHODS: Thirty-six articles from the MEDLINE and EMBASE
      databases were selected for this review. The postnatal outcomes, karyotyping
      results, and sonographic findings of fetal tetralogy of Fallot with pulmonary
      stenosis, tetralogy of Fallot with pulmonary atresia, and tetralogy of Fallot
      with an absent pulmonary valve were collected and compared. RESULTS: The survival
      rates (termination of pregnancy was considered fetal death) for prenatally
      diagnosed tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with
      an absent pulmonary valve at the end of neonatal period were significantly lower
      than the rate for tetralogy of Fallot with pulmonary stenosis (P < .05). The
      survival rate for tetralogy of Fallot with pulmonary atresia was also lower at
      birth (P < .001). Major chromosomal anomalies were more frequently detected in
      tetralogy of Fallot with pulmonary stenosis (P< .05); conversely, 22q11 deletion
      was present more often in fetuses with tetralogy of Fallot with pulmonary atresia
      and tetralogy of Fallot with an absent pulmonary valve (P < .001). Compared to
      tetralogy of Fallot with pulmonary stenosis, a right aortic arch was more
      associated with tetralogy of Fallot with pulmonary atresia (32.6%; P < .05), and
      the ductus arteriosus was almost always absent in tetralogy of Fallot with an
      absent pulmonary valve (87.5%; P < .001). CONCLUSIONS: The postnatal outcomes,
      genetic testing results, and sonographic findings are different among subtypes of
      tetralogy of Fallot. Documenting those details at diagnosis can help specialists
      better counsel their patients.

PMID- 27022173
TI  - Subacute Thyroiditis-An Often Overlooked Sonographic Diagnosis: Report of 3
      Cases.
AB  - The characteristic sonographic finding of subacute thyroiditis of a heterogeneous
      poorly defined hypoechoic area in the thyroid gland may mimic that of thyroid
      malignancy. This finding needs to be interpreted in the correct clinical context
      to avoid an unnecessary biopsy. We describe 3 patients who underwent thyroid
      biopsy on the basis of suspicious sonographic findings but who subsequently had a
      diagnosis of subacute thyroiditis. 

PMID- 27022174
TI  - Assessment of Measurement Repeatability and Reliability With Virtual Touch Tissue
      Quantification Imaging in Cervical Lymphadenopathy.
AB  - OBJECTIVES: The purpose of this study was to prospectively assess the
      repeatability and reliability of 2 measurements of cervical lymphadenopathy using
      Virtual Touch tissue quantification (VTQ) imaging (Siemens Medical Solutions,
      Mountain View, CA) and to analyze the factors affecting the reliability of the
      measurements, including pathologic findings, lesion size and location, and shear
      wave velocities (SWVs). METHODS: In this Institutional Review Board-approved
      prospective study, 92 patients underwent conventional sonography and 2 VTQ
      measurements by acoustic radiation force impulse imaging in a single session. The
      repeatability and reliability of the SWV measurement was determined by using an
      average coefficient of variation (standard deviation/mean) and intraclass
      correlation coefficient (ICC), respectively. By comparing ICCs with a 95%
      confidence interval, the effects of pathologic findings, depth, size, SWV, and
      distance from the carotid artery on reliability were assessed. RESULTS: The mean
      age of the 92 patients included in the study was 51 years (range, 14-77 years).
      The average coefficient of variation was 19.4%. The overall reliability of the 2
      measurements was excellent (ICC, 0.837), but ICCs were significantly decreased in
      lymph nodes in a superficial location (<1 cm) and those with a low SWV (<1.8
      m/s). No significant effect was found on reliability in relation to pathologic
      findings, lesion size, or distance from the carotid artery to the lymph nodes.
      CONCLUSIONS: For SWV measurement by VTQ imaging, the repeatability was 19.4%, and
      reliability was excellent. However, caution is warranted in the use of VTQ
      imaging for superficial soft cervical lymph nodes, as both a superficial location
      and a soft composition tend to be characterized by low reliability of SWV
      findings.

PMID- 27022175
TI  - Olfactory neuroblastoma: A frontal lobe disorder and a runny nose.

PMID- 27022176
TI  - Dural amyloidoma: An unusual presentation of CNS amyloidosis.

PMID- 27022177
TI  - Author Response.

PMID- 27022178
TI  - Mystery Case: Pneumorrhachis: A radiographic diagnosis.

PMID- 27022179
TI  - Pearls & Oy-sters: The importance of atypical features and tracking progression
      in patients misdiagnosed with ALS.

PMID- 27022180
TI  - Clinical Reasoning: Childhood-onset atrophy and spasticity.

PMID- 27022181
TI  - Do women with restless legs syndrome have less bone loss?

PMID- 27022182
TI  - Fuel for the road--sugar transport and pollen tube growth.

PMID- 27022183
TI  - Lights, P450, action! Metabolite formation in chloroplasts.

PMID- 27022184
TI  - Errata.

PMID- 27022185
TI  - Prenatal Diagnosis and Postnatal Follow-up of a Congenital Fibrous Left
      Ventricular Diverticulum.

PMID- 27022186
TI  - Ovarian Teratomas and Anti-N-Methyl-d-Aspartate Receptor Encephalitis: Why
      Sonography First?

PMID- 27022187
TI  - Comment on "Customized Fetal Growth Charts for Parents' Characteristics, Race,
      and Parity by Quantile Regression Analysis: A Cross-sectional Multicenter Italian
      Study".

PMID- 27022188
TI  - Reply.

PMID- 27022189
TI  - Comparison of clinical and pathological characteristics between screen-detected
      and self-detected breast cancers: a Hong Kong study.
AB  - INTRODUCTION: Breast cancer is the leading cause of death of Hong Kong women with
      increasing incidence. This study aimed to determine any prognostic differences
      between screen-detected and self-detected cases of breast cancer in a cohort of
      Hong Kong patients. METHODS: This was a case series with internal comparison
      carried out in a private hospital in Hong Kong. Approximately 3000 cases of
      Chinese patients diagnosed with ductal carcinoma in situ or invasive breast
      cancer were reviewed. RESULTS: The screen-detected group showed better
      pathological characteristics than the self-detected group. Number of lymph nodes
      involved, invasive tumour size, and tumour grade were more favourable in the
      screen-detected group. There was also a lower proportion of patients with pure
      invasive ductal carcinoma and mastectomy in the screen-detected group.
      CONCLUSION: This study provides indirect evidence that women in the local
      population may gain clinical benefit from regular breast cancer screening. The
      findings need to be validated in a representative population of Hong Kong women.

PMID- 27022191
TI  - Knockdown of fast skeletal myosin-binding protein C in zebrafish results in a
      severe skeletal myopathy.
AB  - Myosin-binding protein C (MyBPC) in the muscle sarcomere interacts with several
      contractile and structural proteins. Mutations in the cardiac isoform (MyBPC-3)
      in humans, or animal knockout, are associated with cardiomyopathy. Function of
      the fast skeletal isoform (MyBPC-2) in living muscles is less understood. This
      question was addressed using zebrafish models, combining gene expression data
      with functional analysis of contractility and small-angle x-ray diffraction
      measurements of filament structure. Fast skeletal MyBPC-2B, the major isoform,
      was knocked down by >50% using morpholino antisense nucleotides. These morphants
      exhibited a skeletal myopathy with elevated apoptosis and up-regulation of
      factors associated with muscle protein degradation. Morphant muscles had shorter
      sarcomeres with a broader length distribution, shorter actin filaments, and a
      wider interfilament spacing compared with controls, suggesting that fast skeletal
      MyBPC has a role in sarcomere assembly. Active force was reduced more than
      expected from the decrease in muscle size, suggesting that MyBPC-2 is required
      for optimal force generation at the cross-bridge level. The maximal shortening
      velocity was significantly increased in the MyBPC-2 morphants, but when related
      to the sarcomere length, the difference was smaller, reflecting that the decrease
      in MyBPC-2B content and the resulting myopathy were accompanied by only a minor
      influence on filament shortening kinetics. In the controls, equatorial patterns
      from small-angle x-ray scattering revealed that comparatively few cross-bridges
      are attached (as evaluated by the intensity ratio of the 11 and 10 equatorial
      reflections) during active contraction. X-ray scattering data from relaxed and
      contracting morphants were not significantly different from those in controls.
      However, the increase in the 11:10 intensity ratio in rigor was lower compared
      with that in controls, possibly reflecting effects of MyBPC on the cross-bridge
      interactions. In conclusion, lack of MyBPC-2 results in a severe skeletal
      myopathy with structural changes and muscle weakness. 

PMID- 27022190
TI  - Role of physiological ClC-1 Cl- ion channel regulation for the excitability and
      function of working skeletal muscle.
AB  - Electrical membrane properties of skeletal muscle fibers have been thoroughly
      studied over the last five to six decades. This has shown that muscle fibers from
      a wide range of species, including fish, amphibians, reptiles, birds, and
      mammals, are all characterized by high resting membrane permeability for Cl(-)
      ions. Thus, in resting human muscle, ClC-1 Cl(-) ion channels account for ~80% of
      the membrane conductance, and because active Cl(-) transport is limited in muscle
      fibers, the equilibrium potential for Cl(-) lies close to the resting membrane
      potential. These conditions-high membrane conductance and passive distribution
      enable ClC-1 to conduct membrane current that inhibits muscle excitability. This
      depressing effect of ClC-1 current on muscle excitability has mostly been
      associated with skeletal muscle hyperexcitability in myotonia congenita, which
      arises from loss-of-function mutations in the CLCN1 gene. However, given that ClC
      1 must be drastically inhibited (~80%) before myotonia develops, more recent
      studies have explored whether acute and more subtle ClC-1 regulation contributes
      to controlling the excitability of working muscle. Methods were developed to
      measure ClC-1 function with subsecond temporal resolution in action potential
      firing muscle fibers. These and other techniques have revealed that ClC-1
      function is controlled by multiple cellular signals during muscle activity. Thus,
      onset of muscle activity triggers ClC-1 inhibition via protein kinase C,
      intracellular acidosis, and lactate ions. This inhibition is important for
      preserving excitability of working muscle in the face of activity-induced
      elevation of extracellular K(+) and accumulating inactivation of voltage-gated
      sodium channels. Furthermore, during prolonged activity, a marked ClC-1
      activation can develop that compromises muscle excitability. Data from ClC-1
      expression systems suggest that this ClC-1 activation may arise from loss of
      regulation by adenosine nucleotides and/or oxidation. The present review
      summarizes the current knowledge of the physiological factors that control ClC-1
      function in active muscle.

PMID- 27022192
TI  - The single transmembrane segment determines the modulatory function of the BK
      channel auxiliary gamma subunit.
AB  - The large-conductance, calcium-activated potassium (BK) channels consist of the
      pore-forming, voltage- and Ca(2+)-sensing alpha subunits (BKalpha) and the tissue
      specific auxiliary beta and gamma subunits. The BK channel gamma1 subunit is a
      leucine-rich repeat (LRR)-containing membrane protein that potently facilitates
      BK channel activation in many tissues and cell types through a vast shift in the
      voltage dependence of channel activation by ~140 mV in the hyperpolarizing
      direction. In this study, we found that the single transmembrane (TM) segment
      together with its flanking charged residues is sufficient to fully modulate BK
      channels upon its transplantation into the structurally unrelated beta1 subunit.
      We identified Phe273 and its neighboring residues in the middle of the TM segment
      and a minimum of three intracellular juxtamembrane Arg residues as important for
      the gamma1 subunit's modulatory function and observed functional coupling between
      residues of these two locations. We concluded that the TM segment is a key
      molecular determinant for channel association and modulation and that the
      intracellular positively charged cluster is involved mainly in channel
      association, likely through its TM-anchoring effect. Our findings provide
      insights into the structure-function relationship of the gamma1 subunit in
      understanding its potent modulatory effects on BK channels. 

PMID- 27022193
TI  - TLR10 Is a Negative Regulator of Both MyD88-Dependent and -Independent TLR
      Signaling.
AB  - TLRs are central components of the innate immune system which, upon recognition
      of bacterial, fungal or viral components, activate intracellular signals that
      lead to protective inflammatory responses. Among the 10-member human TLR family,
      TLR10 is the only remaining orphan receptor without a known ligand or signaling
      function. Murine TLR10 is a disrupted pseudogene, which precludes investigation
      using classic gene knockout approaches. We report here that TLR10 suppressed the
      production of an array of cytokines in stably transfected human myelomonocytic
      U937 cells in response to other TLR agonists. This broad TLR suppressive activity
      affects both MyD88- and TRIF-inducing IFN-beta-mediated signaling pathways
      upstream of IkappaB and MAPK activation. Compared with nontransgenic littermate
      controls, monocytes of TLR10 transgenic mice exhibited blunted IL-6 production
      following ex vivo blood stimulation with other TLR agonists. After i.p. injection
      of LPS, lower levels of TNFalpha, IL-6, and type 1 IFN were measured in the serum
      of TLR10 transgenic mice compared to nontransgenic mice, but did not affect mouse
      survival in an LPS-induced septic shock model. Finally, treatment of human
      mononuclear cells with a monoclonal anti-TLR10 Ab suppressed proinflammatory
      cytokines released by LPS stimulation. These results demonstrate that TLR10
      functions as a broad negative regulator of TLR signaling and suggests that TLR10
      has a role in controlling immune responses in vivo.

PMID- 27022194
TI  - HIV-1-Mediated BAFF Secretion in Macrophages Does Not Require Endosomal TLRs,
      Type-I IFN, and Nef, but Depends on the Cellular Phenotype Status.
AB  - HIV-1 infection is characterized by persistent viral replication, chronic immune
      activation, and CD4(+) T cell depletion. Moreover, several immune dysfunctions
      are observed in cells that are not targeted by the virus, such as B cells. Some B
      cell abnormalities include hypergammaglobulinemia, nonspecific B cell activation,
      class switching, increased cell turnover, breakage of tolerance, and a loss of
      the capacity to generate and maintain memory. Several cytokines and growth
      factors that are increased in the serum of HIV-1-infected individuals have been
      suggested to directly or indirectly trigger B cell activation, and one of these
      is BAFF. In this study, we investigate the ability of fully competent (R5-tropic)
      HIV-1 to induce BAFF production by monocyte-derived macrophages (MDMs). We
      demonstrate here that HIV-1 drives BAFF production in MDMs in a type-I IFN- and
      TLR-independent manner. Moreover, we determine that HIV-1 Nef accessory protein
      is dispensable in BAFF upregulation as a nef-deleted HIV-1 strain is still able
      to increase BAFF at levels similar to the wild type strain. Finally, we show that
      the macrophage phenotype status affects HIV-1 replication and BAFF induction, as
      both were abrogated in MDMs displaying a M1 phenotype. This study provides new
      useful information about the increased levels of BAFF observed during HIV-1
      infection and highlights the importance of macrophages as a source of BAFF, a
      phenomenon that might contribute to B cell dysfunctions at inflammatory tissue
      sites in infected individuals.

PMID- 27022195
TI  - Raftlin Controls Lipopolysaccharide-Induced TLR4 Internalization and TICAM-1
      Signaling in a Cell Type-Specific Manner.
AB  - The clathrin-dependent endocytic pathway is crucial for endosomal TLR3- and TLR4
      mediated Toll-IL-1R domain-containing adaptor molecule-1 (TICAM-1) signaling.
      TLR4 uses a different signaling platform, plasma membrane and endosomes, for
      activation of TIRAP-MyD88 and TICAM-2-TICAM-1, respectively. LPS-induced
      endocytosis of TLR4 is mandatory for TICAM-1-mediated signaling including IFN
      beta production. Several molecules/mechanisms such as CD14, clathrin, and
      phosphatidylinositol metabolism have been reported to act as inducers of TLR4
      translocation. However, the molecular mechanism of spatiotemporal regulation of
      TLR4 signaling remains unresolved. We have previously shown that Raftlin is
      essential for clathrin-dependent endocytosis of TLR3 ligand in human epithelial
      cells and myeloid dendritic cells (DCs). In this article, we demonstrate that
      Raftlin also mediated LPS-induced TLR4 internalization and TICAM-1 signaling in
      human monocyte-derived DCs and macrophages (Mo-Mphis). When Raftlin was knocked
      down, LPS-induced TLR4-mediated IFN-beta promoter activation, but not NF-kappaB
      activation, was decreased in HEK293 cells overexpressing TLR4/MD-2 or TLR4/MD
      2/CD14. LPS-induced IFN-beta production by monocyte-derived DCs and Mo-Mphis was
      significantly decreased by knockdown of Raftlin. Upon LPS stimulation, Raftlin
      moved from the cytoplasm to the plasma membrane in Mo-Mphis, where it colocalized
      with TLR4. Raftlin associated with clathrin-associated adaptor protein-2 in
      resting cells and transiently bound to TLR4 and clathrin at the cell surface in
      response to LPS. Thus, Raftlin appears to modulate cargo selection as an
      accessary protein of clathrin-associated adaptor protein-2 in clathrin-mediated
      endocytosis of TLR3/4 ligands.

PMID- 27022196
TI  - Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation
      of Transitional B Cells.
AB  - Mice overexpressing B cell activating factor of the TNF family (BAFF) develop
      systemic autoimmunity characterized by class-switched anti-nuclear Abs.
      Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF
      mediated autoimmunity, but the B cell developmental subsets undergoing TACI
      dependent activation in settings of excess BAFF remain unclear. We report that,
      although surface TACI expression is usually limited to mature B cells, excess
      BAFF promotes the expansion of TACI-expressing transitional B cells. TACI(+)
      transitional cells from BAFF-transgenic mice are characterized by an activated,
      cycling phenotype, and the TACI(+) cell subset is specifically enriched for
      autoreactivity, expresses activation-induced cytidine deaminase and T-bet, and
      exhibits evidence of somatic hypermutation. Consistent with a potential
      contribution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells
      from BAFF-transgenic mice spontaneously produce class-switched autoantibodies ex
      vivo. These combined findings highlight a novel mechanism through which BAFF
      promotes humoral autoimmunity via direct, TACI-dependent activation of
      transitional B cells.

PMID- 27022197
TI  - Restricting Glutamine or Glutamine-Dependent Purine and Pyrimidine Syntheses
      Promotes Human T Cells with High FOXP3 Expression and Regulatory Properties.
AB  - T cell subsets differ in their metabolic requirements, and further insight into
      such differences might be harnessed to selectively promote regulatory T cells
      (Tregs) for therapies in autoimmunity and transplantation. We found that Gln
      restriction during human T cell activation favored CD4 T cells with high
      expression of the Treg transcription factor FOXP3. This resulted from shrinking
      numbers and reduced proliferation of activated FOXP3(lo/-)CD4 T cells while
      FOXP3(hi)CD4 T cell numbers increased. This gain was abolished by blocking Gln
      synthetase, an enzyme that responds to Gln and purine/pyrimidine deficiencies.
      The shift toward FOXP3(hi)CD4 T cells under Gln restriction was recapitulated
      with inhibitors of Gln-dependent pyrimidine and purine syntheses that together
      closely mimicked declining cell numbers and cell cycles, and by small interfering
      RNA knockdown of the respective rate-limiting Gln-consuming enzymes CAD and PPAT.
      FOXP3(hi)-enriched CD25(hi)CD4 T cells from these cultures inhibited
      proliferation, but they also produced effector cytokines, including IL-17A. The
      latter was largely confined to CTLA-4(hi)-expressing FOXP3(hi)-enriched
      CD25(hi)CD4 T cells that suppressed proliferation more weakly than did CTLA-4(lo/
      )CD25(hi)FOXP3(hi)-enriched T cells. A causal link between high IL-17A production
      and impaired suppression of proliferation could not be demonstrated, however.
      Collectively, these results reveal a Gln synthetase-dependent increase and
      resilience of FOXP3(hi) cells under Gln restriction, and they demonstrate that
      impaired Gln-dependent nucleotide synthesis promotes FOXP3(hi) cells with
      regulator properties. It remains to be investigated to what extent the
      concomitant retention of IL-17A-producing CD4 T cells may limit the therapeutic
      potential of Tregs enriched through targeting these pathways in vivo.

PMID- 27022199
TI  - Parent-Child Relationships in Stepfather Families and Adolescent Adjustment: A
      Latent Class Analysis.
AB  - In the current study the authors drew on Waves I and III from Add Health to
      examine the closeness of parent-adolescent relationships in married mother
      stepfather families (N = 1,934). They used latent class analysis to identify
      family constellations defined by adolescents' relationships with all of their
      parents: mothers, stepfathers, and biological nonresident fathers. In particular,
      the authors (a) identified the most common underlying patterns of adolescent
      parent relationships in stepfamilies; (b) determined the background
      characteristics that predict membership in these groups; and (c) examined how
      adolescents in these groups fare with respect to depressive symptoms,
      delinquency, and substance use. The results indicate that adolescents'
      relationships can be represented with 4 latent classes. Adolescents in these
      classes differ on measures of adjustment, and many of these differences persist
      into the early adult years.

PMID- 27022198
TI  - The Ties That Bind: Midlife Parents' Daily Experiences With Grown Children.
AB  - Daily pleasant or stressful experiences with grown children may contribute to
      parental well-being. This diary study focused on midlife parents' (N = 247)
      reports regarding grown children for 7 days. Nearly all parents (96%) had contact
      with a child that week via phone, text, or in person. Nearly all parents shared
      laughter or enjoyable interactions with grown children during the study week.
      More than half of parents experienced stressful encounters (e.g., child got on
      nerves) or stressful thoughts about grown children (e.g., worrying, fretting
      about a problem). Pleasant and stressful experiences with grown children were
      associated with parents' positive and negative daily moods. A pleasant experience
      with a grown child the same day as a stressful experience mitigated effects of
      those stressful experiences on negative mood, however. The findings have
      implications for understanding intergenerational ambivalence and stress buffering
      in this tie.

PMID- 27022200
TI  - Parent Involvement in Head Start and Children's Development: Indirect Effects
      Through Parenting.
AB  - The authors examined the extent to which parent involvement in Head Start
      programs predicted changes in both parent and child outcomes over time, using a
      nationally representative sample of 1,020 three-year-old children over 3 waves of
      the Family and Child Experiences Survey. Center policies that promote involvement
      predicted greater parent involvement, and parents who were more involved in Head
      Start centers demonstrated increased cognitive stimulation and decreased spanking
      and controlling behaviors. In turn, these changes in parenting behaviors were
      associated with gains in children's academic and behavioral skills. These
      findings suggest that Head Start programs should do even more to facilitate
      parent involvement because it can serve as an important means for promoting both
      parent and child outcomes.

PMID- 27022201
TI  - Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality
      Disorder.
AB  - The oxytocin receptor is important in several domains of social behavior, and
      administration of oxytocin modulates social responding in several mammalian
      species, including humans. Oxytocin has both therapeutic and scientific potential
      for elucidating the neural and behavioral mechanisms governing social behavior.
      In the present study, operationally-defined aggressive behavior of six males with
      Antisocial Personality Disorder (ASPD) was measured following acute intranasal
      oxytocin dosing (12, 24, and 48 international units) and placebo, using a well
      validated laboratory task of human aggression (Point-Subtraction Aggression
      Paradigm, or PSAP). The PSAP provides participants with concurrently available
      monetary-earning and operationally-defined aggressive response options,
      maintained by fixed ratio schedules of consequences. Shifts in response rates and
      inter-response time (IRT) distributions were observed on the aggressive response
      option following oxytocin doses, relative to placebo. Few changes were observed
      in monetary-reinforced responding. However, across participants the direction and
      magnitude of changes in aggressive responding were not systematically related to
      dose. No trends were observed between psychometric or physiological data and
      oxytocin dosing or aggressive behavior. While this report is to our knowledge the
      first to examine the acute effects of oxytocin in this population at high risk
      for violence and other forms of antisocial behavior, several limitations in the
      experimental design and the results cast the study as a preliminary report.
      Strategies for more extensive future projects are discussed.

PMID- 27022203
TI  - Racial and Ethnic Differences in the Neighborhood Context of Mastery.

PMID- 27022204
TI  - Scale effects in food environment research: Implications from assessing
      socioeconomic dimensions of supermarket accessibility in an eight-county region
      of South Carolina.
AB  - Choice of neighborhood scale affects associations between environmental
      attributes and health-related outcomes. This phenomenon, a part of the modifiable
      areal unit problem, has been described fully in geography but not as it relates
      to food environment research. Using two administrative-based geographic
      boundaries (census tracts and block groups), supermarket geographic measures
      (density, cumulative opportunity and distance to nearest) were created to examine
      differences by scale and associations between three common U.S. Census-based
      socioeconomic status (SES) characteristics (median household income, percentage
      of population living below poverty and percentage of population with at least a
      high school education) and a summary neighborhood SES z-score in an eight-county
      region of South Carolina. General linear mixed-models were used. Overall, both
      supermarket density and cumulative opportunity were higher when using census
      tract boundaries compared to block groups. In analytic models, higher median
      household income was significantly associated with lower neighborhood supermarket
      density and lower cumulative opportunity using either the census tract or block
      group boundaries, and neighborhood poverty was positively associated with
      supermarket density and cumulative opportunity. Both median household income and
      percent high school education were positively associated with distance to nearest
      supermarket using either boundary definition, whereas neighborhood poverty had an
      inverse association. Findings from this study support the premise that
      supermarket measures can differ by choice of geographic scale and can influence
      associations between measures. Researchers should consider the most appropriate
      geographic scale carefully when conducting food environment studies.

PMID- 27022205
TI  - VOCs Emissions from Multiple Wood Pellet Types and Concentrations in Indoor Air.
AB  - Wood pellet storage safety is an important aspect for implementing woody biomass
      as a renewable energy source. When wood pellets are stored indoors in large
      quantities (tons) in poorly ventilated spaces in buildings, such as in basements,
      off-gassing of volatile organic compounds (VOCs) can significantly affect indoor
      air quality. To determine the emission rates and potential impact of VOC
      emissions, a series of laboratory and field measurements were conducted using
      softwood, hardwood, and blended wood pellets manufactured in New York. Evacuated
      canisters were used to collect air samples from the headspace of drums containing
      pellets and then in basements and pellet storage areas of homes and small
      businesses. Multiple peaks were identified during GC/MS and GC/FID analysis, and
      four primary VOCs were characterized and quantified: methanol, pentane, pentanal,
      and hexanal. Laboratory results show that total VOCs (TVOCs) concentrations for
      softwood (SW) were statistically (p < 0.02) higher than blended or hardwood (HW)
      (SW: 412 +/- 25; blended: 203 +/- 4; HW: 99 +/- 8, ppb). The emission rate from
      HW was the fastest, followed by blended and SW, respectively. Emissions rates
      were found to range from 10-1 to 10-5 units, depending upon environmental
      factors. Field measurements resulted in airborne concentrations ranging from 67
      +/- 8 to 5000 +/- 3000 ppb of TVOCs and 12 to 1500 ppb of aldehydes, with higher
      concentrations found in a basement with a large fabric bag storage unit after
      fresh pellet delivery and lower concentrations for aged pellets. These results
      suggest that large fabric bag storage units resulted in a substantial release of
      VOCs into the building air. Occupants of the buildings tested discussed concerns
      about odor and sensory irritation when new pellets were delivered. The sensory
      response was likely due to the aldehydes.

PMID- 27022206
TI  - Development of a Hydrogen Sulfide End-of-Service-Life Indicator for Respirator
      Cartridges Using Cobinamide.
AB  - An inexpensive paper-based sensor was developed for detecting low ppm
      concentrations of hydrogen sulfide gas. A piece of filter paper containing
      aquohydroxocobinamide [OH(H2O)Cbi] was placed on the end of a bifurcated optical
      fiber, and the reflectance spectrum of the OH(H2O)Cbi was monitored during
      exposure to 10.0 ppm hydrogen sulfide gas (NIOSH recommended exposure limit).
      Reaction of sulfide (HS-) yielded an increase in reflectance from 400-450 nm, and
      decrease from 470-550 nm. Spectral changes were monitored as a function of time
      at 25, 50, and 85% relative humidity. Spectral shifts at high-er humidity
      suggested reduction of the Cbi(III) compound. The sensor was used to detect
      hydrogen sulfide breakthrough from respirator carbon beds and results correlated
      well with a standard electrochemical detector. The simple paper-based sensor
      could provide a real-time end-of-service-life alert for hydrogen sulfide gas.

PMID- 27022208
TI  - Numerical simulation of heat and mass transport during hydration of Portland
      cement mortar in semi-adiabatic and steam curing conditions.
AB  - A model that describes hydration and heat-mass transport in Portland cement
      mortar during steam curing was developed. The hydration reactions are described
      by a maturity function that uses the equivalent age concept, coupled to a heat
      and mass balance. The thermal conductivity and specific heat of mortar with water
      to-cement mass ratio of 0.30 was measured during hydration, using the Transient
      Plane Source method. The parameters for the maturity equation and the activation
      energy were obtained by isothermal calorimetry at 23  degrees C and 38  degrees
      C. Steam curing and semi-adiabatic experiments were carried out to obtain the
      temperature evolution and moisture profiles were assessed by magnetic resonance
      imaging. Three specimen geometries were simulated and the results were compared
      with experimental data. Comparisons of temperature had maximum residuals of 2.5 
      degrees C and 5  degrees C for semi-adiabatic and steam curing conditions,
      respectively. The model correctly predicts the evaporable water distribution
      obtained by magnetic resonance imaging.

PMID- 27022207
TI  - Assessment of Health-Related Quality of Life after TBI: Comparison of a Disease
      Specific (QOLIBRI) with a Generic (SF-36) Instrument.
AB  - Psychosocial, emotional, and physical problems can emerge after traumatic brain
      injury (TBI), potentially impacting health-related quality of life (HRQoL). Until
      now, however, neither the discriminatory power of disease-specific (QOLIBRI) and
      generic (SF-36) HRQoL nor their correlates have been compared in detail. These
      aspects as well as some psychometric item characteristics were studied in a
      sample of 795 TBI survivors. The Shannon H (') index absolute informativity, as
      an indicator of an instrument's power to differentiate between individuals within
      a specific group or health state, was investigated. Psychometric performance of
      the two instruments was predominantly good, generally higher, and more homogenous
      for the QOLIBRI than for the SF-36 subscales. Notably, the SF-36 "Role Physical,"
      "Role Emotional," and "Social Functioning" subscales showed less satisfactory
      discriminatory power than all other dimensions or the sum scores of both
      instruments. The absolute informativity of disease-specific as well as generic
      HRQoL instruments concerning the different groups defined by different correlates
      differed significantly. When the focus is on how a certain subscale or sum score
      differentiates between individuals in one specific dimension/health state, the
      QOLIBRI can be recommended as the preferable instrument. 

PMID- 27022209
TI  - Angiopoietin-2 Is an Early Indicator of Acute Pancreatic-Renal Syndrome in
      Patients with Acute Pancreatitis.
AB  - Within the first week of the disease, acute kidney injury (AKI) is among the most
      common causes of mortality in acute pancreatitis (AP). Recently, serum
      angiopoietin-2 (Ang-2) has been associated with hyperdynamic state of the
      systemic circulation. The aim of this study was to examine the associations
      between Ang-2 and the clinical AP severity during the first 72 hours of the
      disease, and organ disfunction, including AKI. Methods. Study included patients
      admitted to the surgery ward, diagnosed with AP. AKI was diagnosed according to
      KDIGO guidelines and renal failure according to modified Marshall scoring system.
      Ang-2 was determined in serum with ELISA. Results. AP was classified as mild
      (MAP) in 71% of patients, moderately severe (MSAP) in 22%, and severe (SAP) in
      8%. During the first 72 hours of AP, 11 patients developed AKI and 6 developed
      renal failure. Ang-2 at 24, 48, and 72 hours following the onset of AP symptoms
      significantly predicted SAP and MSAP, as well as AKI and renal failure. Also, Ang
      2 significantly correlated with acute phase proteins as well as with the
      indicators of renal disfunction. Conclusions. Serum Ang-2 may be a relevant
      predictor of AP severity, in particular of the development of AP-renal syndrome. 

PMID- 27022210
TI  - Recent Advances in Antiviral Therapy for Chronic Hepatitis C.
AB  - Hepatitis C virus (HCV) infection is a major worldwide health problem. Chronic
      infection induces continuous inflammation in the liver, progression of hepatic
      fibrosis, eventual cirrhosis, and possible hepatocellular carcinoma. Eradication
      of the virus is one of the most important treatment aims. A number of promising
      new direct-acting antivirals (DAAs) have been developed over the past 10 years.
      Due to their increased efficacy, safety, and tolerability, interferon-free oral
      therapies with DAAs have been approved for patients with HCV, including those
      with cirrhosis. This review introduces the characteristics and results of recent
      clinical trials of several DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and
      NS5B inhibitors. DAA treatment failure and prognosis after DAA therapy are also
      discussed. 

PMID- 27022211
TI  - Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory
      Immune Responses to Vaccination.
AB  - Vaccination, designed to trigger a protective immune response against infection,
      is a trigger for mild inflammatory responses. Vaccination studies can address the
      question of inflammation initiation, levels, and resolution as well as its
      regulation for respective studied pathogens. Such studies largely based on
      analyzing the blood components including specific antibodies and cytokines were
      usually constrained by number of participants and volume of collected blood
      sample. Hence, blood-based studies may not be able to cover the full dynamic
      range of inflammation responses induced by vaccination. In this review, the
      potential of using saliva in addition to blood for studying the kinetics of
      inflammatory response studies was assessed. Saliva sampling is noninvasive and
      has a great potential to be used for studies aimed at analysing the magnitude,
      time course, and variance in immune responses, including inflammation after
      vaccination. Based on a literature survey of inflammatory biomarkers that can be
      determined in saliva and an analysis of how these biomarkers could help to
      understand the mechanisms and dynamics of immune reactivity and inflammation, we
      propose that the saliva-based approach might have potential to add substantial
      value to clinical studies, particularly in vulnerable populations such as
      infants, toddlers, and ill individuals. 

PMID- 27022212
TI  - Latest developments in precancerous lesions of hepatocellular carcinoma.
AB  - Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in
      which hepatic precancerous lesions progress into early hepatocellular carcinoma
      (HCC) and progressed HCC, and the close surveillance and treatment of these
      lesions will help improve the survival rates of patients with HCC. The rapid
      development and extensive application of imaging technology have facilitated the
      discovery of nodular lesions of ambiguous significance, such as dysplastic
      nodules. Further investigations showed that these nodules may be hepatic
      precancerous lesions, and they often appear in patients with liver cirrhosis.
      Although the morphology of these nodules is not sufficient to support a diagnosis
      of malignant tumor, these nodules are closely correlated with the occurrence of
      HCC, as indicated by long-term follow-up studies. In recent years, the rapid
      development and wide application of pathology, molecular genetics and imaging
      technology have elucidated the characteristics of precancerous lesions. Based on
      our extensive review of the relevant literature, this article focuses on evidence
      indicating that high-grade dysplastic nodules are more likely to transform into
      HCC than low-grade dysplastic nodules based on clinical, pathological, molecular
      genetic and radiological assessments. In addition, evidence supporting the
      precancerous nature of large cell change in hepatitis B virus-related HCC is
      discussed. 

PMID- 27022213
TI  - Lipids in liver transplant recipients.
AB  - Hyperlipidemia is very common after liver transplantation and can be observed in
      up to 71% of patients. The etiology of lipid disorders in these patients is
      multifactorial, with different lipid profiles observed depending on the
      immunosuppressive agents administered and the presence of additional risk
      factors, such as obesity, diabetes mellitus and nutrition. Due to recent
      improvements in survival of liver transplant recipients, the prevention of
      cardiovascular events has become more important, especially as approximately 64%
      of liver transplant recipients present with an increased risk of cardiovascular
      events. Management of dyslipidemia and of other modifiable cardiovascular risk
      factors, such as hypertension, diabetes and smoking, has therefore become
      essential in these patients. Treatment of hyperlipidemia after liver
      transplantation consists of life style modification, modifying the dose or type
      of immunosuppressive agents and use of lipid lowering agents. At the start of
      administration of lipid lowering medications, it is important to monitor drug
      drug interactions, especially between lipid lowering agents and immunosuppressive
      drugs. Furthermore, as combinations of various lipid lowering drugs can lead to
      severe side effects, such as myopathies and rhabdomyolysis, these combinations
      should therefore be avoided. To our knowledge, there are no current guidelines
      targeting the management of lipid metabolism disorders in liver transplant
      recipients. This paper therefore recommends an approach of managing lipid
      abnormalities occurring after liver transplantation. 

PMID- 27022215
TI  - Deficiency of platelet-derived growth factor receptor-alpha-positive cells in
      Hirschsprung's disease colon.
AB  - AIM: To investigate whether the expression of platelet-derived growth factor
      receptor-alpha-positive (PDGFRalpha(+))-cells is altered in Hirschsprung's
      disease (HD). METHODS: HD tissue specimens (n = 10) were collected at the time of
      pull-through surgery, while colonic control samples were obtained at the time of
      colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of
      PDGFRalpha(+)-cells was visualized using confocal microscopy to assess the
      distribution of these cells, while Western blot analysis was undertaken to
      quantify PDGFRalpha protein expression. RESULTS: Confocal microscopy revealed
      PDGFRalpha(+)-cells within the mucosa, myenteric plexus and smooth muscle in
      normal controls, with a marked reduction in PDGFRalpha(+)-cells in the HD
      specimens. Western blotting revealed high levels of PDGFRalpha protein expression
      in normal controls, while there was a striking decrease in PDGFRalpha protein
      expression in the HD colon. CONCLUSION: These findings suggest that the altered
      distribution of PDGFRalpha(+)-cells in both the aganglionic and ganglionic HD
      bowel may contribute to the motility dysfunction in HD.

PMID- 27022214
TI  - Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A
      review.
AB  - Liver transplantation (LT) has been accepted as an effective therapy for
      hepatocellular carcinoma (HCC). The Milan criteria (MC) are widely used across
      the world to select LT candidates in HCC patients. However, the MC may be too
      strict because a substantial subset of patients who have HCC exceed the MC and
      who would benefit from LT may be unnecessarily excluded from the waiting list. In
      recent years, many extended criteria beyond the MC were raised, which were proved
      to be able to yield similar outcomes compared with those patients meeting the MC.
      Because the simple use of tumor size and number was insufficient to indicate HCC
      biological features and to predict the risk of tumor recurrence, some biological
      markers such as Alpha-fetoprotein, Des-Gamma-carboxy prothrombin and the
      neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC
      patients beyond the MC. For patients with advanced HCC, downstaging therapy is an
      effective way to reduce the tumor stage to fulfill the MC by using liver-directed
      therapy such as transarterial chemoembolization, radiofrequency ablation and
      percutaneous ethanol injection. This article reviews the recent advances in LT
      for HCC beyond the MC. 

PMID- 27022202
TI  - Advancing biomaterials of human origin for tissue engineering.
AB  - Biomaterials have played an increasingly prominent role in the success of
      biomedical devices and in the development of tissue engineering, which seeks to
      unlock the regenerative potential innate to human tissues/organs in a state of
      deterioration and to restore or reestablish normal bodily function. Advances in
      our understanding of regenerative biomaterials and their roles in new tissue
      formation can potentially open a new frontier in the fast-growing field of
      regenerative medicine. Taking inspiration from the role and multi-component
      construction of native extracellular matrices (ECMs) for cell accommodation, the
      synthetic biomaterials produced today routinely incorporate biologically active
      components to define an artificial in vivo milieu with complex and dynamic
      interactions that foster and regulate stem cells, similar to the events occurring
      in a natural cellular microenvironment. The range and degree of biomaterial
      sophistication have also dramatically increased as more knowledge has accumulated
      through materials science, matrix biology and tissue engineering. However,
      achieving clinical translation and commercial success requires regenerative
      biomaterials to be not only efficacious and safe but also cost-effective and
      convenient for use and production. Utilizing biomaterials of human origin as
      building blocks for therapeutic purposes has provided a facilitated approach that
      closely mimics the critical aspects of natural tissue with regard to its physical
      and chemical properties for the orchestration of wound healing and tissue
      regeneration. In addition to directly using tissue transfers and transplants for
      repair, new applications of human-derived biomaterials are now focusing on the
      use of naturally occurring biomacromolecules, decellularized ECM scaffolds and
      autologous preparations rich in growth factors/non-expanded stem cells to either
      target acceleration/magnification of the body's own repair capacity or use
      nature's paradigms to create new tissues for restoration. In particular, there is
      increasing interest in separating ECMs into simplified functional domains and/or
      biopolymeric assemblies so that these components/constituents can be discretely
      exploited and manipulated for the production of bioscaffolds and new biomimetic
      biomaterials. Here, following an overview of tissue auto-/allo-transplantation,
      we discuss the recent trends and advances as well as the challenges and future
      directions in the evolution and application of human-derived biomaterials for
      reconstructive surgery and tissue engineering. In particular, we focus on an
      exploration of the structural, mechanical, biochemical and biological information
      present in native human tissue for bioengineering applications and to provide
      inspiration for the design of future biomaterials.

PMID- 27022217
TI  - Ultrasound virtual endoscopy: Polyp detection and reliability of measurement in
      an in vitro study with pig intestine specimens.
AB  - AIM: To present our initial experience regarding the feasibility of ultrasound
      virtual endoscopy (USVE) and its measurement reliability for polyp detection in
      an in vitro study using pig intestine specimens. METHODS: Six porcine intestine
      specimens containing 30 synthetic polyps underwent USVE, computed tomography
      colonography (CTC) and optical colonoscopy (OC) for polyp detection. The polyp
      measurement defined as the maximum polyp diameter on two-dimensional (2D)
      multiplanar reformatted (MPR) planes was obtained by USVE, and the absolute
      measurement error was analyzed using the direct measurement as the reference
      standard. RESULTS: USVE detected 29 (96.7%) of 30 polyps, remaining a 7-mm one
      missed. There was one false-positive finding. Twenty-six (89.7%) of 29
      reconstructed images were clearly depicted, while 29 (96.7%) of 30 polyps were
      displayed on CTC with one false-negative finding. In OC, all the polyps were
      detected. The intraclass correlation coefficient was 0.876 (95%CI: 0.745-0.940)
      for measurements obtained with USVE. The pooled absolute measurement errors +/-
      the standard deviations of the depicted polyps with actual sizes <= 5 mm, 6-9 mm,
      and >= 10 mm were 1.9 +/- 0.8 mm, 0.9 +/- 1.2 mm, and 1.0 +/- 1.4 mm,
      respectively. CONCLUSION: USVE is reliable for polyp detection and measurement in
      in vitro study.

PMID- 27022216
TI  - Auphen and dibutyryl cAMP suppress growth of hepatocellular carcinoma by
      regulating expression of aquaporins 3 and 9 in vivo.
AB  - AIM: To investigate whether the regulation of aquaporin 3 (AQP3) and AQP9 induced
      by Auphen and dibutyryl cAMP (dbcAMP) inhibits hepatic tumorigenesis. METHODS:
      Expression of AQP3 and AQP9 was detected by Western blot, immunohistochemistry
      (IHC), and RT-PCR in HCC samples and paired non-cancerous liver tissue samples
      from 30 hepatocellular carcinoma (HCC) patients. A xenograft tumor model was used
      in vivo. Nine nude mice were divided into control, Auphen-treated, and dbcAMP
      treated groups (n = 3 for each group). AQP3 and AQP9 protein expression after
      induction of xenograft tumors was detected by IHC and mRNA by RT-PCR analysis.
      The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay
      and histological evaluation were used to detect apoptosis of tumor cells, and the
      concentration of serum alpha-fetoprotein (AFP) was measured using RT-PCR and an
      ELISA kit. RESULTS: The volumes and weights of tumors decreased significantly in
      the Auphen- and dbcAMP-treated mice compared with the control mice (P < 0.01).
      The levels of AQP3 were significantly lower in the Auphen treatment group, and
      levels of AQP9 were significantly higher in thedbcAMP treatment mice than in the
      control mice (P < 0.01). The reduction of AQP3 by Auphen and increase of AQP9 by
      dbcAMP in nude mice suppressed tumor growth of HCC, which resulted in reduced AFP
      levels in serum and tissues, and apoptosis of tumor cells in the Auphen- and
      dbcAMP-treated mice, when compared with control mice (P < 0.01). Compared with
      para-carcinoma tissues, AQP3 expression increased in tumor tissues whereas the
      expression of AQP9 decreased. By correlating clinicopathological and expression
      levels, we demonstrated that the expression of AQP3 and AQP9 was correlated with
      clinical progression of HCC and disease outcomes. CONCLUSION: AQP3 increases in
      HCC while AQP9 decreases. Regulation of AQP3 and AQP9 expression by Auphen and
      dbcAMP inhibits the development and growth of HCC.

PMID- 27022218
TI  - Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites.
AB  - AIM: To investigate the role of tolvaptan in regulating aquaporin (AQP)-2
      expression and fecal water content in cirrhotic rats with ascites. METHODS:
      Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4
      for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups
      (vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five
      subgroups (days 1, 2, 3, 4, and 5). Blood samples were obtained to measure
      vasopressin and sodium concentrations. Rats were killed and colonic mucosa was
      scraped for analysis of protein expression and AQP-2 transcriptional level. The
      whole layer was fixed for hematoxylin&eosin (HE) staining and feces were
      collected for determination of fecal water content. CONCLUSION: Compared with
      vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2
      to a similar level in each treatment group. AQP-2 showed significant upregulation
      in cirrhotic rats with ascites compared with an untreated control group (100% +/-
      22.9% vs 22.2% +/- 10.23%, P < 0.01). After administration of tolvaptan, AQP-2
      expression began to decrease significantly from day 2 in each treatment group,
      but no significant difference was finally found between the treatment groups.
      Fecal water content in the distal colon was increased by 5 mg/kg tolvaptan on day
      1 (66.8% +/- 9.3% vs 41.4% +/- 6.3%, in the vehicle group, P < 0.05). Fecal water
      content returned to baseline at day 4 at the latest in both treatment groups, and
      did not correspond to the change in AQP-2 expression. HE staining of the colonic
      mucosa showed no mucosal damage related to tolvaptan. CONCLUSION: Upregulation of
      AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan
      inhibits its expression and may decrease water reabsorption and induce diarrhea.

PMID- 27022219
TI  - Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer
      in Taiwan.
AB  - AIM: To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and
      APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk.
      METHODS: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and
      736 age- and sex-matched healthy controls from a medical center in Taiwan.
      Genomic DNA isolated from the buffy coat was used for genotyping through
      polymerase chain reaction. Unconditional logistic regressions were used for
      calculating ORs and 95%CIs to determine the association between the genetic
      polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE
      software. Moreover, stratification analyses on the basis of sex, age at
      diagnosis, and tumor subsite and stage were performed. RESULTS: The CRC risk was
      higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI:
      1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer
      (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype.
      In addition, OGG1 11657G allele carriers had a 41% reduced CRC risk among stage 0
      II patients (OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher
      among females with the APE1 Glu allele (OR = 1.41, 95%CI: 1.02-1.96). The APE1
      148Glu/-656G haplotype was also associated with a significant CRC risk in females
      (OR = 1.36, 95%CI: 1.03-1.78). CONCLUSION: OGG1 and APE1 polymorphisms are
      associated with stage- and sex-specific risk of CRC in the Taiwanese population.

PMID- 27022220
TI  - Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph
      node metastases in pancreatobiliary carcinoma.
AB  - AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic
      ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma.
      METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph
      nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In
      the primary analysis, patients with successful EUS-fine needle aspiration (FNA)
      were included. The lymph nodes were assessed by several standard EUS variables
      (short and long axis lengths, shape, edge characteristic and echogenicity), color
      Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS
      variable (heterogeneous/homogeneous enhancement patterns). The diagnostic
      accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage
      diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent
      surgical resection. RESULTS: One hundred and nine patients (143 lymph nodes)
      fulfilled the criteria. The short axis cut-off >= 13 mm predicted malignancy with
      a sensitivity and specificity of 72% and 85%, respectively. These values were 72%
      and 63% for the long axis cut-off >= 20 mm, 62% and 75% for the round shape
      variable, 81% and 30% for the sharp edge variable, 66% and 61% for the
      hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and
      91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was
      more accurate than standard and color Doppler EUS, except the short axis cut-off.
      Notably, three patients excluded because of EUS-FNA failure were correctly N
      staged by CH-EUS. CONCLUSION: CH-EUS complements standard and color Doppler EUS
      and EUS-FNA for assessment of lymph node metastases.

PMID- 27022221
TI  - Donor preoperative oxygen delivery and post-extubation hypoxia impact donation
      after circulatory death hypoxic cholangiopathy.
AB  - AIM: To evaluate donation after circulatory death (DCD) orthotopic liver
      transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and
      donor risk-conditions. METHODS: From 2003-2013, 45 DCD donor transplants were
      performed. Predonation physiologic data from UNOS DonorNet included preoperative
      systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and
      hemoglobin. Mean arterial blood pressure was computed from the systolic and
      diastolic blood pressures. Donor preoperative arterial O2 content was computed as
      [hemoglobin (gm/dL) * 1.37 (mL O2/gm) * SpO2%) + (0.003 * PaO2)]. The amount of
      preoperative donor red blood cell transfusions given and vasopressor use during
      the intensive care unit stay were documented. Donors who were transfused >= 1
      unit of red-cells or received >= 2 vasopressors in the preoperative period were
      categorized as the red-cell/multi-pressor group. Following withdrawal of life
      support, donor ischemia time was computed as the number-of-minutes from onset of
      diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia
      time was the number-of-minutes from onset of pulse oximetry < 80% until clamping.
      Donor hypoxia score was (ischemia time + hypoxemia time) / donor preoperative
      hemoglobin. RESULTS: The 1, 3, and 5 year graft and patient survival rates were
      83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16%
      requiring retransplant. HC occurred in donors with increased age (33.0 +/- 10.6
      years vs 25.6 +/- 8.4 years, P = 0.014), less preoperative multiple vasopressors
      or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin
      (10.7 +/- 2.2 gm/dL vs 12.3 +/- 2.1 gm/dL, P = 0.017), lower preoperative
      arterial oxygen content (14.8 +/- 2.8 mL O2/100 mL blood vs 16.8 +/- 3.3 mL
      O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P =
      0.006), and increased preoperative mean arterial pressure (92.7 +/- 16.2 mmHg vs
      83.8 +/- 18.5 mmHg, P = 0.10). HC was independently associated with age, multi
      pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and
      mean arterial pressure (r(2) = 0.6197). The transplantation rate was greater for
      the later period with more liberal donor selection [era 2 (7.1/year)], compared
      to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and
      in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to
      asystole (14.4 +/- 4.7 m vs 9.3 +/- 4.5 m, P = 0.001), ischemia (13.9 +/- 5.9 m
      vs 9.7 +/- 5.6 m, P = 0.03), and hypoxemia (16.0 +/- 5.1 m vs 11.1 +/- 6.7 m, P =
      0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006).
      CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an
      objective measure of DCD liver transplantation risk for recipient HC. Donor
      selection criteria influence HC rates.

PMID- 27022222
TI  - Intrahepatic distribution of hepatitis B virus antigens in patients with and
      without hepatocellular carcinoma.
AB  - AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg)
      and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and
      without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B
      patients (mean age of 40.3 +/- 2.5 years), comprising of 14 HBeAg positive and 19
      HBeAg negative patients; and 13 patients with hepatitis B virus related
      hepatocellular carcinoma (mean age of 49.6 +/- 4.7 years), were included in our
      study. Immunohistochemical staining for HBcAg and HBsAg was done using standard
      streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver
      biopsies. The HBcAg and HBsAg staining distributions and patterns were described
      according to a modified classification system. RESULTS: Compared to the HBeAg
      negative patients, the HBeAg positive patients were younger, had higher mean HBV
      DNA and alanine transaminases levels. All the HBeAg positive patients had
      intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and
      "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg
      negative patients had intrahepatic HBcAg staining. However, the intrahepatic
      HBsAg staining has wider distribution among the HBeAg negative patients, namely;
      majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to
      "rare" distribution among the HBeAg positive cases. All but one patient with HCC
      were HBeAg negative with either undetectable HBV DNA or very low level of
      viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the
      HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral
      therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues
      but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively.
      CONCLUSION: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of
      patients with suppressed HBV DNA on antiviral therapy; that may predispose them
      to cancer development.

PMID- 27022223
TI  - Two strategies for prevention of cytomegalovirus infections after liver
      transplantation.
AB  - AIM: To analyze differences in patients' clinical course, we compared two regimes
      of either preemptive therapy or prophylaxis after liver transplantation. METHODS:
      This retrospective study was reviewed and approved by the institutional review
      board of the University of Leipzig. Cytomegalovirus (CMV) prophylaxis with
      valganciclovir hydrochloride for liver transplant recipients was replaced by a
      preemptive strategy in October 2009. We retrospectively compared liver transplant
      recipients 2 years before and after October 2009. During the first period, all
      patients received valganciclovir daily. During the second period all patients
      included in the analysis were treated following a preemptive strategy. Outcomes
      included one year survival and therapeutic intervention due to CMV viremia or
      infection. RESULTS: Between 2007 and 2010 n = 226 patients underwent liver
      transplantation in our center. n = 55 patients were D(+)/R(-) high risk
      recipients and were excluded from further analysis. A further 43 patients had to
      be excluded since CMV prophylaxis/preemptive strategy was not followed although
      there was no clinical reason for the deviation. Of the remaining 128 patients
      whose data were analyzed, 60 received prophylaxis and 68 were treated following a
      preemptive strategy. The difference in overall mortality was not significant, nor
      was it significant for one-year mortality where it was 10% (95%CI: 8%-28%, P =
      0.31) higher for the preemptive group. No significant differences in blood count
      abnormalities or the incidence of sepsis and infections were observed other than
      CMV. In total, 19 patients (14.7%) received ganciclovir due to CMV viremia and/or
      infections. Patients who were treated according to the preemptive algorithm had a
      significantly higher rate risk of therapeutic intervention with ganciclovir [n =
      16 (23.5%) vs n = 3 (4.9%), P = 0.003)]. CONCLUSION: These data suggest that CMV
      prophylaxis is superior to a preemptive strategy in patients undergoing liver
      transplantation.

PMID- 27022225
TI  - Intracorporeal esophagojejunostomy after totally laparoscopic total gastrectomy:
      A single-center 7-year experience.
AB  - AIM: To assess the efficacy and safety of intracorporeal esophagojejunostomy in
      patients undergoing laparoscopic total gastrectomy (LTG) for gastric cancer.
      METHODS: A retrospective review of 81 consecutive patients who underwent LTG with
      the same surgical team between November 2007 and July 2014 was performed. Four
      types of intracorporeal esophagojejunostomy using staplers or hand-sewn suturing
      were performed after LTG. Data on clinicopatholgoical characteristics, occurrence
      of complications, postoperative recovery, anastomotic time, and operation time
      among the surgical groups were obtained through medical records. RESULTS: The
      average operation time was 288.7 min, the average anastomotic time was 54.3 min,
      and the average estimated blood loss was 82.7 mL. There were no cases of
      conversion to open surgery. The first flatus was observed around 3.7 d, while the
      liquid diet was started, on average, from 4.9 d. The average postoperative
      hospital stay was 10.1 d. Postoperative complications occurred in 14 patients,
      nearly 17.3%. However, there were no cases of postoperative death. CONCLUSION:
      LTG performed with intracorporeal esophagojejunostomy using laparoscopic staplers
      or hand-sewn suturing is feasible and safe. The surgical results were acceptable
      from the perspective of minimal invasiveness.

PMID- 27022224
TI  - Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus
      genotype 1.
AB  - AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa
      2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype
      (GT) 1-infected patients. METHODS: In this phase 3, randomized, open-label,
      noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs
      telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC),
      cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype
      (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total
      of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or
      telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received
      24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic
      response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24
      wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus
      pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The
      primary objective was to compare for noninferiority of sustained virologic
      response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key
      secondary objectives were to demonstrate that the rates of anemia (hemoglobin <
      10 g/dL) and rash-related events, through week 12, were lower with daclatasvir +
      pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients.
      Resistance testing was performed using population-based sequencing of the NS5A
      region for all patients at baseline, and for patients with virologic failure or
      relapse and HCV-RNA >= 1000 IU/mL, to investigate any link between NS5A
      polymorphisms associated with daclatasvir resistance and virologic outcome.
      RESULTS: Patient demographics and disease characteristics were generally balanced
      across treatment arms; however, there was a higher proportion of black/African
      Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups,
      respectively) than in the telaprevir groups (2.2% and 3.0%). Among GT1b-infected
      patients, daclatasvir plus pegIFN/RBV was noninferior to telaprevir plus
      pegIFN/RBV for SVR12 [85% (228/268) vs 81% (109/134); difference, 4.3% (95%CI: 
      3.3% to 11.9%)]. Anemia (hemoglobin < 10 g/dL) was significantly less frequent
      with daclatasvir than with telaprevir [difference, -29.1% (95%CI: -38.8% to 
      19.4%)]. Rash-related events were also less common with daclatasvir than with
      telaprevir, but the difference was not statistically significant. In GT1a
      infected patients, SVR12 was 64.9% with daclatasvir and 69.7% with telaprevir.
      Among both daclatasvir and telaprevir treatment groups, across GT1b- or GT1a
      infected patients, lower response rates were observed in patients with IL28B non
      CC and cirrhosis - factors known to affect response to pegIFN/RBV. Consistent
      with these observations, a multivariate logistic regression analysis in GT1b
      infected patients demonstrated that SVR12 was associated with IL28B host genotype
      (CC vs non-CC, P = 0.011) and cirrhosis status (absent vs present, P = 0.031).
      NS5A polymorphisms associated with daclatasvir resistance (at L28, R30, L31, or
      Y93) were observed in 17.3% of GT1b-infected patients at baseline; such variants
      did not appear to be absolute predictors of failure since 72.1% of these patients
      achieved SVR12 compared with 86.9% without these polymorphisms. Among GT1b
      infected patients, treatment was completed by 85.4% (229/268) in the daclatasvir
      group, and by 85.1% (114/134) in the telaprevir group, and among GT1a-infected
      patients, by 67.2% (90/134) and 69.7% (46/66), respectively. Discontinuations (of
      all 3 agents) due to an AE were more frequent with telaprevir than with
      daclatasvir, whereas discontinuations due to lack of efficacy were more frequent
      with daclatasvir, due, in part, to differences in futility criteria. CONCLUSION:
      Daclatasvir plus pegIFN/RBV demonstrated noninferiority to telaprevir plus
      pegIFN/RBV for SVR12 and was well-tolerated in treatment-naive GT1b-infected
      patients, supporting the use of daclatasvir with other direct-acting antivirals.

PMID- 27022226
TI  - Osteopontin: A non-invasive parameter of portal hypertension and prognostic
      marker of cirrhosis.
AB  - AIM: To investigate the relationship between osteopontin plasma concentrations
      and the severity of portal hypertension and to assess osteopontin prognostic
      value. METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112
      ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous
      pressure gradient (HVPG) measurement and laboratory and ultrasound examinations
      were carried out for all patients. HVPG was measured using a standard
      catheterization method with the balloon wedge technique. Osteopontin was measured
      using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients
      were followed up with a specific focus on mortality. The control group consisted
      of 137 healthy age- and sex- matched individuals. RESULTS: The mean value of HVPG
      was 16.18 +/- 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in
      cirrhotic patients were significantly higher (P < 0.001). The plasma levels of
      osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed
      among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL
      osteopontin distinguished patients with significant portal hypertension (HVPG
      above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of
      patients was 3.7 +/- 2.6 years. The probability of cumulative survival was 39%
      for patients with HVPG > 10 mmHg and 65% for those with HVPG <= 10 mmHg (P =
      0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76).
      Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin
      values above 80 ng/mL had significantly lower cumulative survival compared to
      those with osteopontin <= 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI:
      1.06-4.68). CONCLUSION: Osteopontin is a non-invasive parameter of portal
      hypertension that distinguishes patients with clinically significant portal
      hypertension. It is a strong prognostic factor for survival.

PMID- 27022227
TI  - Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea
      predominant irritable bowel syndrome and ulcerative colitis.
AB  - AIM: To study differences in the visceral sensitivity of the colonic mucosa
      between patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and
      those with ulcerative colitis (UC) in remission and to relate these differences
      with changes in the 5-hydroxytryptophan (5-HT) signaling pathway. METHODS:
      Gastrointestinal symptoms were used to determine the clinical symptom scores and
      rectal visceral sensitivity of patients with IBS-D and patients with UC in
      remission. Blood levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were
      measured using an HPLC-electrochemical detection system. The levels of 5-HT 3
      receptor (3R), 4R, and 7R mRNAs in colonic biopsy samples were detected using
      reverse transcription-polymerase chain reaction. The protein expression of TPH1
      was analyzed by Western blot and immunohistochemistry. RESULTS: Abdominal pain or
      discomfort, stool frequency, and the scores of these symptoms in combination with
      gastrointestinal symptoms were higher in the IBS-D and UC groups than in the
      control groups. However, no significant differences were observed between the IBS
      D and UC remission groups. With respect to rectal visceral sensitivity, the UC
      remission and IBS-D groups showed a decrease in the initial perception threshold,
      defecating threshold and pain threshold. However, these groups exhibited
      significantly increased anorectal relaxation pressure. Tests examining the main
      indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5
      HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3R and 5-HT5R
      expression were increased in both the IBS-D and the UC remission groups; no
      increases were observed with respect to 5-HT7R expression. CONCLUSION: The IBS-D
      and UC groups showed similar clinical symptom scores, visceral sensitivity, and
      levels of serotonin signaling pathway indicators in the plasma and colonic
      mucosa. However, the pain threshold and 5-HT7R expression in the colonic mucosa
      were significantly different between these groups. The results reveal that (1)
      IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical
      manifestations of these conditions and (2) the observed differences in visceral
      hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor,
      a component of the 5-HT signaling pathway.

PMID- 27022228
TI  - Cost-effectiveness analysis of population-based screening of hepatocellular
      carcinoma: Comparing ultrasonography with two-stage screening.
AB  - AIM: To assess the cost-effectiveness of two population-based hepatocellular
      carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and
      mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we
      applied a Markov decision model with a societal perspective and a lifetime
      horizon for the general population-based cohorts in an area with high HCC
      incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was
      estimated from published meta-analyses. The costs of surveillance, diagnosis, and
      treatment were based on a combination of published literature, Medicare payments,
      and medical expenditure at the National Taiwan University Hospital. The main
      outcome measure was cost per life-year gained with a 3% annual discount rate.
      RESULTS: The results show that the mass screening using AUS was associated with
      an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas
      two-stage screening was associated with an incremental cost-effectiveness ratio
      of USD49733 per life-year gained, as compared with no screening. Screening
      programs with an initial screening age of 50 years old and biennial screening
      interval were the most cost-effective. These findings were sensitive to the costs
      of screening tools and the specificity of biomarker screening. CONCLUSION: Mass
      screening using AUS is more cost effective than two-stage biomarker-ultrasound
      screening. The most optimal strategy is an initial screening age at 50 years old
      with a 2-year inter-screening interval.

PMID- 27022230
TI  - Helicobacter pylori eradication therapy for functional dyspepsia: Systematic
      review and meta-analysis.
AB  - AIM: To evaluate whether Helicobacter pylori (H. pylori) eradication therapy
      benefits patients with functional dyspepsia (FD). METHODS: Randomized controlled
      trials (RCTs) investigating the efficacy and safety of H. pylori eradication
      therapy for patients with functional dyspepsia published in English (up to May
      2015) were identified by searching PubMed, EMBASE, and The Cochrane Library.
      Pooled estimates were measured using the fixed or random effect model. Overall
      effect was expressed as a pooled risk ratio (RR) or a standard mean difference
      (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0. RESULTS:
      This systematic review included 25 RCTs with a total of 5555 patients with FD.
      Twenty-three of these studies were used to evaluate the benefits of H. pylori
      eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12
      1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement
      during long-term follow-up at >= 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001)
      but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P =
      0.27). Seven studies showed no benefit of H. pylori eradication therapy on
      quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six
      studies demonstrated that H. pylori eradication therapy reduced the development
      of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI:
      0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy
      increased the likelihood of treatment-related side effects compared to no
      eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies
      demonstrated that patients who received H. pylori eradication therapy were more
      likely to obtain histologic resolution of chronic gastritis compared to those who
      did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001).
      CONCLUSION: The decision to eradicate H. pylori in patients with functional
      dyspepsia requires individual assessment.

PMID- 27022232
TI  - Ileus caused by cholesterol crystal embolization: A case report.
AB  - Cholesterol crystal embolization (CCE) is a rare systemic embolism caused by
      formation of cholesterol crystals from atherosclerotic plaques. CCE usually
      occurs during vascular manipulation, such as vascular surgery or endovascular
      catheter manipulation, or due to anticoagulation or thrombolytic therapy. We
      report a rare case of intestinal obstruction caused by spontaneous CCE. An 81
      year-old man with a history of hypertension was admitted for complaints of
      abdominal pain, bloating, and anorexia persisting for 4 mo. An abdominal computed
      tomography revealed intestinal ileus. His symptoms were immediately relieved by
      an ileus tube insertion, and he was discharged 6 d later. However, these symptoms
      immediately reappeared and persisted, and partial resection of the small
      intestine was performed. A histopathological examination indicated that small
      intestine obstruction was caused by CCE. At the 12-mo follow-up, the patient
      showed no evidence of CCE recurrence. Thus, in cases of intestinal obstruction,
      CCE should also be considered. 

PMID- 27022231
TI  - Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.
AB  - Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local
      progression with possible systemic dissemination. We report a case of a patient
      affected by MF with a pancreatic mass that was a diagnostic challenge between
      primitive tumor and pancreatic metastasis from MF. Clinical setting findings and
      imaging studies raised the suspicion of a pancreatic primary neoplasm. A
      diagnostic clue was provided by the combined histomorphologic/immunohistochemical
      study of pancreatic and cutaneous biopsies, which revealed a pancreatic
      localization of MF. Considering the rarity of metastatic localization of MF to
      the pancreas, we next investigated whether chemokine-chemokine receptor
      interactions could be involved in the phenomenon to provide new insight into the
      possible mechanisms underlying metastatic localization of MF to the pancreas.
      Histological analyses of archival pancreatic tissue demonstrated that glucagon
      secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may
      have attracted in our case metastatic MF cells expressing the complementary
      receptor CCR10.

PMID- 27022234
TI  - An Unconventional Inchworm Actuator Based on PZT/ERFs Control Technology.
AB  - An unconventional inchworm actuator for precision positioning based on
      piezoelectric (PZT) actuation and electrorheological fluids (ERFs) control
      technology is presented. The actuator consists of actuation unit (PZT stack
      pump), fluid control unit (ERFs valve), and execution unit (hydraulic actuator).
      In view of smaller deformation of PZT stack, a new structure is designed for
      actuation unit, which integrates the advantages of two modes (namely, diaphragm
      type and piston type) of the volume changing of pump chamber. In order to improve
      the static shear yield strength of ERFs, a composite ERFs valve is designed,
      which adopts the series-parallel plate compound structure. The prototype of the
      inchworm actuator has been designed and manufactured in the lab. Systematic test
      results indicate that the displacement resolution of the unconventional inchworm
      actuator reaches 0.038 MUm, and the maximum driving force and velocity are 42 N,
      14.8 mm/s, respectively. The optimal working frequency for the maximum driving
      velocity is 120 Hz. The complete research and development processes further
      confirm the feasibility of developing a new type of inchworm actuator with high
      performance based on PZT actuation and ERFs control technology, which provides a
      reference for the future development of a new type of actuator. 

PMID- 27022233
TI  - Primary splenic angiosarcoma with liver metastasis: A case report and literature
      review.
AB  - Primary splenic angiosarcoma (PSA) is an unusual and highly malignant vascular
      tumour with a high rate of metastatic. Moreover, the research on prognosis of the
      disease is poor. The epidemiology, etiology, clinical diagnosis and treatment of
      the disease remain challenging, because case reports of the disease are few in
      number. In accordance with other malignant tumors, PSA is very aggressive, and
      the majority of patients in which this disease is found are at an advanced stage.
      Almost all patients die within 12 mo of diagnosis irrespective of treatment. We
      report here a woman who had complained of upper bellyache and anorexia for 10 d.
      Magnetic resonance imaging showed enlargement of the spleen with multiple
      heterogeneous masses in the lower pole of the spleen. A hand-assisted
      laparoscopic splenectomy was performed which allowed histopathologic diagnosis.
      The patient was diagnosed with PSA and liver metastasis, and succumbed to the
      disease 35 d after surgery. The literature was finished combined with the
      clinical features, diagnosis and management of PSA.

PMID- 27022235
TI  - Experiment Research on Hot-Rolling Processing of Nonsmooth Pit Surface.
AB  - In order to achieve the nonsmooth surface drag reduction structure on the inner
      polymer coating of oil and gas pipelines and improve the efficiency of pipeline
      transport, a structural model of the machining robot on the pipe inner coating is
      established. Based on machining robot, an experimental technique is applied to
      research embossing and coating problems of rolling-head, and then the molding
      process rules under different conditions of rolling temperatures speeds and depth
      are analyzed. Also, an orthogonal experiment analysis method is employed to
      analyze the different effects of hot-rolling process apparatus on the embossed
      pits morphology and quality of rolling. The results also reveal that elevating
      the rolling temperature or decreasing the rolling speed can also improve the pit
      structure replication rates of the polymer coating surface, and the rolling feed
      has little effect on replication rates. After the rolling-head separates from the
      polymer coating, phenomenon of rebounding and refluxing of the polymer coating
      occurs, which is the reason of inability of the process. A continuous hot-rolling
      method for processing is used in the robot and the hot-rolling process of the
      processing apparatus is put in a dynamics analysis. 

PMID- 27022229
TI  - Glucose metabolic phenotype of pancreatic cancer.
AB  - AIM: To construct a global "metabolic phenotype" of pancreatic ductal
      adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.
      METHODS: A systematic review of the literature was performed using OvidSP and
      PubMed databases using keywords "pancreatic cancer" and individual glycolytic and
      mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal
      studies investigating the oncological effect of enzyme expression changes and
      inhibitors in both an in vitro and in vivo setting were included in the review.
      Data reporting changes in enzyme expression and the effects on PDAC cells, such
      as survival and metastatic potential, were extracted to construct a metabolic
      phenotype. RESULTS: Seven hundred and ten papers were initially retrieved, and
      were screened to meet the review inclusion criteria. 107 unique articles were
      identified as reporting data involving glycolytic enzymes, and 28 articles
      involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol.
      There is consistent over-expression of glycolytic enzymes and lactate
      dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine
      triphosphate production from glycolysis. Certain isoforms of these enzymes were
      over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA,
      enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect
      on PDAC, thus identifying these as potential therapeutic targets. However, the
      Warburg effect on MOP enzymes is less clear, with different expression levels at
      different points in the Krebs cycle resulting in a fundamental change of
      metabolite levels, suggesting that other essential anabolic pathways are being
      stimulated. CONCLUSION: Further characterisation of the PDAC metabolic phenotype
      is necessary as currently there are few clinical studies and no successful
      clinical trials targeting metabolic enzymes.

PMID- 27022236
TI  - Femtosecond lasers for laser in situ keratomileusis: a systematic review and meta
      analysis.
AB  - PURPOSE: The aim of this study was to review and meta-analyze whether there are
      differences between reported femtosecond (FS) lasers for laser-assisted in situ
      keratomileusis (LASIK) in terms of efficacy, predictability, and safety as
      primary outcomes and corneal flap thickness measurements and pre- and
      postoperative complications as secondary outcomes. METHODS: A comprehensive
      literature search of PubMed, Science Direct, Scopus, and Cochrane CENTRAL Trials
      Library databases was conducted to identify the relevant prospective randomized
      controlled trials of FS lasers for LASIK. Thirty-one articles describing a total
      of 5,404 eyes were included. RESULTS: Based on efficacy, IntraLase FS 10 and 30
      kHz gave the best results. Based on predictability and safety, there were no
      differences between various FS lasers. FEMTO LDV and IntraLase FS 60 kHz produced
      the most accurate flap thicknesses. IntraLase and Wavelight SF200 had the fewest
      intraoperative complications. IntraLase, Visumax, and Wavelight FS200 had the
      most seldom postoperative complications. CONCLUSION: There were dissimilarities
      between different FS lasers based on efficacy and intraoperative and
      postoperative complications. All FS lasers were predictable and safe for making
      corneal flaps in LASIK.

PMID- 27022237
TI  - Clinical trial comparing autogenous fascia lata sling and Gore-Tex suspension in
      bilateral congenital ptosis.
AB  - PURPOSE: To study the effect of autogenous fascia lata sling (AFLS) versus Gore
      Tex suspension (GTS) regarding the functional and aesthetic outcomes in patients
      with bilateral congenital ptosis. PATIENTS AND METHODS: A prospective comparative
      randomized single-center study enrolled 110 patients with bilateral congenital
      ptosis. One group (n=55) underwent AFLS and the second group (n=55) underwent
      GTS. Exclusion criteria were good levator function, absent Bell's phenomenon, and
      abnormal ocular motility. Follow-up period was 2 years. Functional outcome was
      measured from digital photos by analysis of upper eyelid margin position relative
      to the superior limbus and classified as very good (<3 mm), good (3-5 mm), poor
      (>5 mm), and recurrent. Aesthetic outcome was assessed in terms of lid contour,
      symmetry of eyelid height, and lid crease presence. Complications were also
      reported. RESULTS: Failure rate (recurrence and complications) was less in AFLS
      (P=0.035). Symmetrical lid height and good contour were more frequently attained
      by AFLS (P=0.007 and 0.047, respectively). However, the frequency of very good,
      good, poor, recurrence, lagopthalmos, ectropion, infection, and formed lid crease
      individually showed no statistically significant difference (P=0.252, 0.482, 1,
      0.489, 0.438, 1, 0.618, and 0.506, respectively). CONCLUSION: AFLS is a better
      choice in surgery for patients with bilateral congenital ptosis because it has
      fewer complications and a lesser recurrence rate than GTS.

PMID- 27022238
TI  - Role of aflibercept for macular edema following branch retinal vein occlusion:
      comparison of clinical trials.
AB  - For years, the standard of care for branch-retinal-vein-occlusion-associated
      macular edema was initial observation followed by grid-pattern laser
      photocoagulation for persistent edema. Newer pharmacologic options have
      revolutionized the management of branch-retinal-vein-occlusion-associated macular
      edema, and the visual outcomes of these eyes are better than ever. However, a
      variety of available treatment options including intravitreal corticosteroids and
      intravitreal anti-vascular endothelial growth factor agents have established
      novel challenges with regard to appropriate drug selection. This review
      summarizes the available clinical studies with special emphasis on the comparison
      of intravitreal aflibercept with ranibizumab, bevacizumab, and steroid agents. 

PMID- 27022239
TI  - An evaluation of the safety and efficacy of bimatoprost for eyelash growth in
      pediatric subjects.
AB  - PURPOSE: Evaluate the safety and effectiveness of bimatoprost 0.03% for treatment
      of eyelash hypotrichosis in a pediatric population. PATIENTS AND METHODS: This
      multicenter, randomized, double-masked, parallel-group study was conducted at
      seven sites in the US and Brazil. Subjects with eyelash hypotrichosis caused by
      chemotherapy or alopecia areata (aged 5-17 years) or healthy adolescents aged 15
      17 years were enrolled (N=71). Subjects applied bimatoprost 0.03% or vehicle to
      upper eyelid margins once nightly for 4 months and were followed for 1 month post
      treatment. Eyelash prominence was assessed using the validated 4-grade Global
      Eyelash Assessment scale with photonumeric guide. Changes in eyelash length,
      thickness, and darkness were measured by digital image analysis. Safety was
      assessed by adverse events and ophthalmic observations. RESULTS: Eyelash
      prominence improved in a significantly greater proportion of subjects treated
      with bimatoprost compared with vehicle at month 4 (70.8% versus 26.1%; P<0.001).
      This benefit was sustained at month 5 post-treatment assessment. Digital image
      analysis measures were significantly improved with bimatoprost. Significant
      treatment benefits with bimatoprost versus vehicle were evident among the healthy
      adolescents but not in the postchemotherapy or alopecia areata subgroups. The
      safety profile of bimatoprost was consistent with previous studies in adults.
      CONCLUSION: Bimatoprost was safe and well tolerated in pediatric subjects with
      eyelash hypotrichosis. In this study with limited sample size, subgroup analyses
      showed that treatment was effective in healthy adolescents with no concurrent
      contributing medical condition, but not in those with eyelash hypotrichosis due
      to chemotherapy or alopecia areata.

PMID- 27022240
TI  - Selective biologics for ulcerative colitis and Crohn's disease - clinical utility
      of vedolizumab.
AB  - Inflammatory bowel disease (IBD) encompasses a cluster of different disease
      phenotypes which are broadly classified into ulcerative colitis and Crohn's
      disease. Disease pathogenesis is driven by abnormal host immune responses to
      their resident gut microbiome in genetically susceptible individuals. Clinical
      disease features and outcomes are heterogenous and not unexpected as over 163
      genetic loci are associated with disease susceptibility, and there are great
      variability in environmental exposures. Despite this variability, there has been
      relatively few efficacious therapies for particularly moderate-to-severe IBD.
      Treatment has been dominated by antitumor necrosis alpha agents with significant
      success but equally potentially serious adverse events. Therapeutic targeting of
      leucocyte trafficking has emerged as a viable alternative therapy, with
      vedolizumab being the lead compound. This review focuses primarily on its
      biological function as a selective gut immunotherapy, its safety and efficacy,
      and its emerging role as a mainstream therapy in managing IBD. 

PMID- 27022242
TI  - Stability studies of lincomycin hydrochloride in aqueous solution and intravenous
      infusion fluids.
AB  - PURPOSE: The purpose of this study was to evaluate the chemical stability of
      Lincocin((r)) (lincomycin hydrochloride) in commonly used intravenous fluids at
      room temperature (25 degrees C), at accelerated-degradation temperatures and in
      selected buffer solutions. MATERIALS AND METHODS: The stability of Lincocin((r))
      injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25
      degrees C+/-0.1 degrees C in sodium lactate (Hartmann's), 0.9% sodium chloride,
      5% glucose, and 10% glucose solutions was investigated over 31 days. Forced
      degradation of Lincocin((r)) in hydrochloric acid, sodium hydroxide, and hydrogen
      peroxide was performed at 60 degrees C. The effect of pH on the degradation rate
      of lincomycin hydrochloride stored at 80 degrees C was determined. RESULTS:
      Lincomycin hydrochloride w as found to maintain its shelf life at 25 degrees C in
      sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose
      solution, and 10% glucose solution, with less than 5% lincomycin degradation
      occurring in all intravenous solutions over a 31-day period. Lincomycin
      hydrochloride showed less rapid degradation at 60 degrees C in acid than in basic
      solution, but degraded rapidly in hydrogen peroxide. At all pH values tested,
      lincomycin followed first-order kinetics. It had the greatest stability near pH 4
      when stored at 80 degrees C (calculated shelf life of 4.59 days), and was least
      stable at pH 2 (calculated shelf life of 0.38 days). CONCLUSION: Lincocin((r))
      injection was chemically found to have a shelf life of at least 31 days at 25
      degrees C when added to sodium lactate (Hartmann's) solution, 0.9% sodium
      chloride solution, 5% glucose solution, and 10% glucose solution. Solutions
      prepared at approximately pH 4 are likely to have optimum stability.

PMID- 27022241
TI  - Celastrol inhibits prostaglandin E2-induced proliferation and osteogenic
      differentiation of fibroblasts isolated from ankylosing spondylitis hip tissues
      in vitro.
AB  - BACKGROUND: Heterotopic ossification on the enthesis, which develops after
      subsequent inflammation, is one of the most distinctive features in ankylosing
      spondylitis (AS). Prostaglandin E2 (PGE-2) serves as a key mediator of
      inflammation and bone remodeling in AS. Celastrol, a well-known Chinese medicinal
      herb isolated from Tripterygium wilfordii, is widely used in treating
      inflammatory diseases, including AS. It has been proven that it can inhibit
      lipopolysac-charide-induced expression of various inflammation mediators, such as
      PGE-2. However, the mechanism by which celastrol inhibits inflammation-induced
      bone forming in AS is unclear. OBJECTIVE: To investigate whether celastrol could
      inhibit isolated AS fibroblast osteogenesis induced by PGE-2. METHODS: Hip
      synovial tissues were obtained from six AS patients undergoing total hip
      replacement in our hospital. Fibroblasts were isolated, primarily cultured, and
      then treated with PGE-2 for osteogenic induction. Different doses of celastrol
      and indometacin were added to observe their effects on osteogenic
      differentiation. Cell proliferation, osteogenic markers, alizarin red staining as
      well as the activity of alkaline phosphatase were examined in our study. RESULTS:
      Celastrol significantly inhibits cell proliferation of isolated AS fibroblasts
      and in vitro osteogenic differentiation compared with control groups in a time-
      and dose-dependent manner. CONCLUSION: Our results demonstrated that celastrol
      could inhibit isolated AS fibroblast proliferation and in vitro osteogenic
      differentiation. The interaction of PI3K/AKT signaling and Wnt protein may be
      involved in the process. Further studies should be performed in vivo and animal
      models to identify the potential effect of celastrol on the bone metabolism of AS
      patients.

PMID- 27022243
TI  - Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human
      adrenocortical carcinoma treatment.
AB  - BACKGROUND: It has been demonstrated that chloroquine (CQ) enhances the efficacy
      of chemotherapy. However, little is known about whether CQ could enhance the
      efficacy of cisplatin (DDP) in the treatment of adrenocortical carcinoma (ACC).
      In this study, we explore the efficacy and mechanism by which CQ affects DDP
      sensitivity in human ACC in vitro and in vivo. METHODS: The autophagic gene
      Beclin-1 expression was detected by immunohistochemistry, and the protein levels
      were analyzed using immunoblotting assays of ACC tissues and normal adrenal
      cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell
      viability assay was performed using the MTT method. Qualitative autophagy
      detection was performed by monodansylcadaverine staining of autophagic vacuoles.
      Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to
      count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1,
      LC3, and p62) and apoptosis relative protein (Bax and Bcl-2) levels were
      evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c
      mice bearing SW13 cell xenografts was established to evaluate the efficacy of
      concomitant therapy. RESULTS: The expression of the autophagic gene Beclin-1 was
      significantly downregulated in ACC tissues compared to normal adrenal cortex
      tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal
      adrenal cortex tissues (P<0.05). In vitro concomitant therapy (DDP and CQ) was
      more effective in restraining SW13 cell proliferation. DDP could promote cell
      apoptosis and induce autophagy in SW13 cells. Concomitant therapy further
      promoted cell apoptosis by inhibiting autophagy. In vivo, we found that
      concomitant therapy was more potent than DDP monotherapy in inhibiting the growth
      of xenografted tumors and prolonging the survival of tumor-bearing mice.
      CONCLUSION: The antitumor ability of DDP was related to autophagy activity, and
      the concomitant therapy (DDP and CQ) could be an optimal strategy for treating
      ACC.

PMID- 27022244
TI  - Efficacy and safety of modified-release prednisone in patients with rheumatoid
      arthritis.
AB  - The introduction of modified-release (MR) prednisone adds a drug with encouraging
      potential to the armamentarium of the rheumatologist. In particular, for patients
      experiencing a reduced quality of life due to prolonged morning stiffness, it is
      a promising therapeutic approach. Two clinical trials and one open-label
      observational study investigated the effectiveness of MR prednisone in reducing
      rheumatoid arthritis-related morning stiffness for both new and current users of
      corticosteroids. The efficacy and safety of MR prednisone use in rheumatoid
      arthritis patients are reviewed in this article. This includes pivotal trials as
      well as pathophysiological considerations and clinical implications. 

PMID- 27022245
TI  - RGD(F/S/V)-Dex: towards the development of novel, effective, and safe
      glucocorticoids.
AB  - Dexamethasone (Dex) is an effective glucocorticoid in treating inflammation and
      preventing rejection reaction. However, the side effects limit its clinical
      application. To improve its druggable profile, the conjugates of RGD-peptide
      modified Dex were presented and their enhanced anti-inflammation activity,
      minimized osteoporotic action, and nanoscaled assembly were explored. (RGD stands
      for Arg-Gly-Asp. Standard single letter biochemical abbreviations for amino acids
      have been used throughout this paper.) In respect of the rejection reaction, the
      survival time of the implanted myocardium of the mice treated with 1.43 umol/kg/d
      of the conjugates for 15 consecutive days was significantly longer than that of
      the mice treated with 2.5 umol/kg/d of Dex, and the conjugates, but not Dex,
      exhibited no toxic action. At a single dose of 14.3 umol/kg (100 times minimal
      effective dose, 0.143 umol/kg), the conjugates induced no liver, kidney, or
      systemic toxicity. At the dose of 1.43 umol/kg, the conjugates, but not Dex,
      prolonged the bleeding time of the mice, and inhibited the thrombosis of the
      rats. In water and rat plasma, the conjugates formed nanoparticles of 14-250 and
      101-166 nm in diameter, respectively. Since the nanoparticles of ~100 nm in size
      cannot be entrapped by macrophages in the circulation, RGDF-Dex would
      particularly be worthy of development, since its nanoparticle diameter is 101 nm.

PMID- 27022246
TI  - Protective effects of honokiol on ischemia/reperfusion injury of rat ovary: an
      experimental study.
AB  - AIM: The purpose of this study was to investigate the protective effect of
      honokiol on experimental ischemia/reperfusion injury of rat ovary. MATERIALS AND
      METHODS: A total of 40 female Wistar albino rats were used in this study. The
      rats were divided into five groups as follows: sham (Group I), torsion (Group
      II), torsion + detorsion (Group III), torsion + detorsion + saline (Group IV),
      and torsion + detorsion + honokiol (Group V). Bilateral adnexa in all the rats
      except for those in the sham group were exposed to torsion for 3 hours. The rats
      in Group IV were administered saline, whereas the rats in Group V were
      administered honokiol by intraperitoneal route 30 minutes before detorsion.
      Tissue and plasma concentrations of malondialdehyde and nitric oxide were
      determined. Ovarian tissue was histologically evaluated. Data analyses were
      performed by means of Kruskal-Wallis test and Mann-Whitney U-test (Bonferroni
      correction) in SPSS 15.0 (Statistical Package for Social Sciences; SPSS Inc.,
      Chicago, IL, USA). RESULTS: The torsion and detorsion groups had higher scores in
      vascular congestion, hemorrhage, and inflammatory cell infiltration compared with
      the sham group (P<0.005). In addition, total histopathological scores were
      significantly higher in the torsion and detorsion groups compared with the sham
      group (P<0.005). A significant reduction was observed in hemorrhage, inflammatory
      cell infiltration, and cellular degeneration scores, of all histopathological
      scores, in the honokiol group (P<0.005). Ovarian tissue concentrations of
      malondialdehyde were significantly higher in the torsion and detorsion groups
      compared with the sham and honokiol groups (P<0.005). Ovarian tissue
      concentrations of nitric oxide, on the other hand, were significantly higher in
      the torsion group compared with the sham, saline, and honokiol groups (P<0.005).
      CONCLUSION: Honokiol has a beneficial effect on ovarian torsion-related
      ischemia/reperfusion injury.

PMID- 27022248
TI  - Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for
      treatment of atopic dermatitis.
AB  - Silymarin is a naturally occurring flavonoid drug; evidence from recent research
      has highlighted its use as a potential treatment for atopic dermatitis (AD). Both
      poor water solubility and drug permeability have hindered the percutaneous
      absorption of silymarin. Formulation of silymarin into pluronic-lecithin
      organogel (PLO) basis for topical skin delivery is the main aim of this work. Six
      different PLO formulations were prepared containing various pluronic to lecithin
      ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide.
      Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for
      topical delivery of silymarin as it showed optimum pH, viscosity, drug content,
      and satisfactory in vitro silymarin permeation. The silymarin PLO formulation
      significantly relieved inflammatory symptoms of AD such as redness, swelling, and
      inflammation. These findings warrant the ability for application of these novel
      silymarin PLO formulations as a novel treatment for AD. 

PMID- 27022247
TI  - Spotlight on botulinum toxin and its potential in the treatment of stroke-related
      spasticity.
AB  - Poststroke spasticity affects up to one-half of stroke patients and has
      debilitating effects, contributing to diminished activities of daily living,
      quality of life, pain, and functional impairments. Botulinum toxin (BoNT) is
      proven to be safe and effective in the treatment of focal poststroke spasticity.
      The aim of this review is to highlight BoNT and its potential in the treatment of
      upper and lower limb poststroke spasticity. We review evidence for the efficacy
      of BoNT type A and B formulations and address considerations of optimal injection
      technique, patient and caregiver satisfaction, and potential adverse effects of
      BoNT. 

PMID- 27022249
TI  - Better health-related quality of life (mental component summary), having a higher
      level of education, and being less than 75 years of age are predictors of
      hospital admission among cognitively intact nursing home residents: a 5-year
      follow-up study.
AB  - OBJECTIVE: To study whether health-related quality of life (HRQOL), activities of
      daily living (ADL), and anxiety and depression symptoms affect the risk of
      hospital admission and potential interactions with having a cancer diagnosis.
      METHODS: This study was a prospective observational study with 5-year follow-up
      and analyzed the follow-up data on hospital admissions until 2010 using baseline
      data from 227 cognitively intact nursing home (NH) residents (60 of whom had
      cancer) in 2004-2005. Data on HRQOL were collected by using the Short Form-36
      Health Survey, divided into physical component summary (PCS) and mental component
      summary (MCS), and symptoms of anxiety and depression were collected by using the
      Hospital Anxiety and Depression Scale (HADS). ADL were obtained from registered
      observation and sociodemographic variables, diagnoses, and hospital admissions
      from the NH records. Personal identification numbers were linked to the record
      systems of the hospitals, thereby registering all hospital admissions. We
      analyzed the time elapsing between inclusion and the first hospital admission.
      RESULTS: Residents with higher HRQOL (MCS) had significantly more hospital
      admissions after adjustment for age, sex, marital status, education, and
      comorbidity. HRQOL (PCS), ADL, depression, and anxiety symptoms were not
      associated with hospital admissions. Cancer increased the risk after adjustment
      for all other risk factors but did not increase the effects of MCS, PCS, ADL, or
      depression or anxiety symptoms. Having a higher level of education and being less
      than 75 years of age were associated with hospitalization. The residents
      diagnosed with cancer had the most days in hospital related to diseases of the
      respiratory system and cancer, and diseases of the circulatory and respiratory
      systems were more frequent among the residents without a cancer diagnosis.
      CONCLUSION: Better self-reported HRQOL (MCS) was associated with hospital
      admissions, whereas self-reported HRQOL (PCS), ADL, and depression and anxiety
      symptoms were not. Cancer increased the risk but not the effects of MCS, PCS,
      ADL, or depression or anxiety symptoms. Having a higher level of education and
      being less than 75 years of age were also associated with hospitalization.

PMID- 27022250
TI  - Public opinion on community-based education and exercise programs for managing
      hip and knee osteoarthritis-like symptoms: results of a survey.
AB  - INTRODUCTION: In North America, delivery of targeted exercise and education
      programs by health professionals for people with hip and knee osteoarthritis (OA)
      poses challenges related to cost and access. Linking the wellness and health
      sectors could increase program availability. We evaluated if people with OA were
      willing to participate in programs delivered by trainers in community
      centers/gyms. METHODS: We conducted an online survey of the general public in
      Canada over a period of 2 months. Participants included those aged >=30 years
      with self-reported chronic OA-like knee or hip pain. We evaluated access to
      community/fitness centers, exercise frequency, interest in attending an evidence
      based program twice a week for 6 weeks, and willingness to pay. Analyses included
      descriptive statistics with 95% confidence intervals and chi-square tests to
      evaluate factors associated with willingness to attend the program. RESULTS:
      After removing duplicate records, 751 respondents completed the survey with 408
      likely having hip and/or knee OA and never having received a joint replacement.
      These 408 respondents had an age range of 30 to >=75 years and 86% were female.
      Of the 408, (63.7%) were between 45 and 64 years of age. Only two respondents
      reported that a community center was >1 hour away. One hundred and fifty-six
      (38%) reported a current membership, and 203 (50.4%) reported exercise 3 days/wk,
      120 (29.8%) <3 days, and 80 (19.9%) reported no exercise. Two hundred and ninety
      seven respondents (73.7%) were willing to attend a program, and, of these, 26%
      were willing to pay $100 Cdn or more. Age, sex, access to a community center/gym,
      current gym membership, and current frequency of exercise were not significantly
      associated with willingness to attend a program. CONCLUSION: Almost 75% of
      respondents with OA, despite one in three having a community center membership,
      were interested in attending a targeted program delivered in community/fitness
      centers. A program in the wellness sector may be a viable option to support
      people in managing their hip and or knee OA.

PMID- 27022251
TI  - Impact of overweight and obesity on the musculoskeletal system using lumbosacral
      angles.
AB  - BACKGROUND: Overweight and obesity have been identified as independent risk
      factors for musculoskeletal disorders. However, the association between obesity
      and low back pain remains controversial. Little is known about the effects of
      overweight and obesity on the angles of the lumbosacral spine. The objective of
      this study was to evaluate the effects of body mass index (BMI) and waist-hip
      ratio (WHR) on lumbosacral angles. METHODS: The effects of BMI and WHR on the
      lumbar lordosis angle (LLA), lumbosacral angle (LSA), sacral inclination angle (
      degrees  degrees ), and lumbosacral disc angle (LSDA) of 174 overweight and obese
      subjects (test group) and 126 underweight and normal-weight subjects (control
      group) were analyzed. RESULTS: The test group had a significantly higher mean
      LSA, LLA, sacral inclination angle (SIA), and LSDA (P=0.001). A significant
      correlation was noted between BMI and LSA (P=0.001), LLA (P=0.001), SIA
      (P=0.001), and LSDA (P=0.03). There was also a positive relationship between WHR
      and LSA (P=0.012), LLA (P=0.009), SIA (P=0.02), and LSDA (P=0.01). CONCLUSION:
      There was an increase in lumbosacral angles in individuals with raised BMI and
      WHR. This may result in biomechanical changes in the lumbosacral spine, which
      increase the incidence of low back pain.

PMID- 27022252
TI  - Legal medical consideration of Alzheimer's disease patients' dysgraphia and
      cognitive dysfunction: a 6 month follow up.
AB  - BACKGROUND: The purpose of this study was to investigate the ability of
      Alzheimer's disease (AD) patients to express intentions and desires, and their
      decision-making capacity. This study examines the findings from a 6-month follow
      up of our previous results in which 30 patients participated. MATERIALS AND
      METHODS: The patient's cognition was examined by conducting the tests of 14
      questions and letter-writing ability over a period of 19 days, and it was
      repeated after 6 months. The difference between these two cognitive measures (PQ1
      before-PQ2 before), tested previously and later the writing test, was designated
      DDelta before. The test was repeated after 6 months, and PQ1 after-PQ2 after was
      designated DDelta after. RESULTS: Several markedly strong relationships between
      dysgraphia and other measures of cognitive performance in AD patients were
      observed. The most aged patients (over 86 years), despite less frequency,
      maintain the cognitive capacity manifested in the graphic expressions. A
      document, written by an AD patient presents an honest expression of the patient's
      intention if that document is legible, clear, and comprehensive. CONCLUSION: The
      identification of impairment/deficits in writing and cognition during different
      phases of AD may facilitate the understanding of disease progression and identify
      the occasions during which the patient may be considered sufficiently lucid to
      make decisions.

PMID- 27022253
TI  - Utilization of arm span instead of height in body mass index calculation in
      elderly subjects.

PMID- 27022254
TI  - Periprocedural temporary pacing in primary percutaneous coronary intervention for
      patients with acute inferior myocardial infarction.
AB  - OBJECTIVE: High-degree atrioventricular block (AVB), including complete AVB in
      acute inferior ST-elevation myocardial infarction (STEMI), is not uncommon.
      However, there is no study evaluating the clinical differences between patients
      who have undergone temporary pacing (TP) and patients who have not. The present
      study was designed to investigate whether TP has any prognostic significance in
      inferior STEMI complicated by complete AVB. METHODS: From January 2009 to
      December 2014, 295 consecutive patients diagnosed with inferior wall STEMI in a
      university hospital were reviewed. All of them underwent primary percutaneous
      coronary intervention (PCI). Among the 295 patients, there were 72 patients with
      complete AVB. The clinical characteristics, procedural data, and long-term major
      adverse cardiocerebrovascular events were compared in patients with and without
      TP. RESULTS: Baseline clinical and procedural characteristics were similar
      between patients with and without TP. Patients with TP were more likely to
      present with cardiogenic shock; thus, additional interventions were attempted via
      a femoral approach, as patients received further treatment with intra-aortic
      balloon pumps and were subjected to additional cardiopulmonary resuscitation.
      Most cases of complete AVB were primarily caused by right coronary artery
      occlusion. After a median follow-up period of 344 (range, 105.5-641) days, major
      adverse cardiocerebrovascular events did not differ between the groups (P=0.528).
      CONCLUSION: We conclude that primary PCI without TP is acceptable in complete AVB
      complicated acute inferior STEMI. To avoid delay in reperfusion, we suggest that
      primary PCI should be the first priority therapy rather than treating patients
      initially with TP.

PMID- 27022255
TI  - Whakawhanaungatanga: the importance of culturally meaningful connections to
      improve uptake of pulmonary rehabilitation by Maori with COPD - a qualitative
      study.
AB  - BACKGROUND: Pulmonary rehabilitation is known to improve function and quality of
      life for people with chronic obstructive pulmonary disease (COPD). However,
      little research has been conducted on the influence of culture on experiences of
      pulmonary rehabilitation. This study examined factors influencing uptake of
      pulmonary rehabilitation by Maori with COPD in New Zealand. METHOD: Grounded
      theory nested within kaupapa Maori methodology. Transcripts were analyzed from
      interviews and focus groups with 15 Maori and ten New Zealand non-Maori invited
      to attend pulmonary rehabilitation for COPD. Maori participants had either
      attended a mainstream hospital-based program, a community-based program designed
      "by Maori, for Maori", or had experienced both. RESULTS: Several factors
      influencing uptake of pulmonary rehabilitation were common to all participants
      regardless of ethnicity: 1) participants' past experiences (eg, of exercise; of
      health care systems), 2) attitudes and expectations, 3) access issues (eg, time,
      transport, and conflicting responsibilities), and 4) initial program experiences.
      These factors were moderated by the involvement of family and peers, interactions
      with health professionals, the way information on programs was presented, and by
      new illness events. For Maori, however, several additional factors were also
      identified relating to cultural experiences of pulmonary rehabilitation. In
      particular, Maori participants placed high value on whakawhanaungatanga: the
      making of culturally meaningful connections with others. Culturally appropriate
      communication and relationship building was deemed so important by some Maori
      participants that when it was absent, they felt strongly discouraged to attend
      pulmonary rehabilitation. Only the more holistic services offered a program in
      which they felt culturally safe and to which they were willing to return for
      ongoing rehabilitation. CONCLUSION: Lack of attention to cultural factors in the
      delivery of pulmonary rehabilitation may be a barrier to its uptake by
      indigenous, minority ethnic groups, such as New Zealand Maori. Indigenous-led or
      culturally responsive health care interventions for COPD may provide a solution
      to this issue.

PMID- 27022256
TI  - Apoptosis inducing ability of silver decorated highly reduced graphene oxide
      nanocomposites in A549 lung cancer.
AB  - Recently, graphene and graphene-based materials have been increasingly used for
      various biological applications due to their extraordinary physicochemical
      properties. Here, we demonstrate the anticancer properties and apoptosis-inducing
      ability of silver doped highly reduced graphene oxide nanocomposites synthesized
      by employing green approach. These nano composites (PGE-HRG-Ag) were synthesized
      by using Pulicaria glutinosa extract (PGE) as a reducing agent and were evaluated
      for their anticancer properties against various human cancer cell lines with
      tamoxifen as the reference drug. A correlation between the amount of Ag
      nanoparticles on the surface of highly reduced graphene oxide (HRG) and the
      anticancer activity of nanocomposite was observed, wherein an increase in the
      concentration of Ag nanoparticles on the surface of HRG led to the enhanced
      anticancer activity of the nanocomposite. The nanocomposite PGE-HRG-Ag-2
      exhibited more potent cytotoxicity than standard drug in A549 cells, a human lung
      cancer cell line. A detailed investigation was undertaken and Fluorescence
      activated cell sorting (FACS) analysis demonstrated that the nanocomposite PGE
      HRG-Ag-2 showed G0/G1 phase cell cycle arrest and induced apoptosis in A549
      cells. Studies such as, measurement of mitochondrial membrane potential,
      generation of reactive oxygen species (ROS) and Annexin V-FITC staining assay
      suggested that this compound induced apoptosis in human lung cancer cells.

PMID- 27022257
TI  - Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid
      nanoemulsions in melanoma-bearing mice.
AB  - PURPOSE: Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL)
      receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase
      PTX antitumoral action. The administration of simvastatin (Simva), which lowers
      LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX
      associated with LDE (LDE-PTX). MATERIALS AND METHODS: B16F10 melanoma-bearing
      mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and
      Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 MUmol/kg (three
      intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9
      consecutive days. RESULTS: Compared with saline controls, 95% tumor-growth
      inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and
      Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only
      37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups.
      Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE
      PTX and Simva group presented tumors with reduced cellular density and increased
      collagen fibers I and III. Tumors from all groups showed reduction in
      immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva
      presented the lowest MMP-9 expression. Expression of p21 was increased in the
      Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva
      groups, expression of cyclin D1, a proliferation and survival promoter of tumor
      cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity
      compared with PTX and Simva, which resulted in weight loss and myelosuppression.
      CONCLUSION: Simva increased the antitumor activity of PTX carried in LDE but not
      of PTX commercial presentation, possibly because statins increase the expression
      of LDL receptors that internalize LDE-PTX.

PMID- 27022258
TI  - Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae.
AB  - Copper oxide nanoparticles (CuO NPs) are used for a variety of purposes in a wide
      range of commercially available products. Some CuO NPs probably end up in the
      aquatic systems, thus raising concerns about aqueous exposure toxicity, and the
      impact of CuO NPs on liver development and neuronal differentiation remains
      unclear. In this study, particles were characterized using Fourier transform
      infrared spectra, scanning electron microscopy, and transmission electron
      microscopy. Zebrafish embryos were continuously exposed to CuO NPs from 4 hours
      postfertilization at concentrations of 50, 25, 12.5, 6.25, or 1 mg/L. The
      expression of gstp1 and cyp1a was examined by quantitative reverse transcription
      polymerase chain reaction. The expression of tumor necrosis factor alpha and
      superoxide dismutase 1 was examined by quantitative reverse transcription
      polymerase chain reaction and Western blotting. Liver development and retinal
      neurodifferentiation were analyzed by whole-mount in situ hybridization,
      hematoxylin-eosin staining, and immunohistochemistry, and a behavioral test was
      performed to track the movement of larvae. We show that exposure of CuO NPs at
      low doses has little effect on embryonic development. However, exposure to CuO
      NPs at concentrations of 12.5 mg/L or higher leads to abnormal phenotypes and
      induces an inflammatory response in a dose-dependent pattern. Moreover, exposure
      to CuO NPs at high doses results in an underdeveloped liver and a delay in
      retinal neurodifferentiation accompanied by reduced locomotor ability. Our data
      demonstrate that short-term exposure to CuO NPs at high doses shows
      hepatotoxicity and neurotoxicity in zebrafish embryos and larvae. 

PMID- 27022259
TI  - Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely
      exposed to amorphous silica nanoparticles.
AB  - The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can
      lead to human exposure by injection, skin penetration, ingestion, or inhalation.
      However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on
      multiple organs and the mechanisms underlying these effects are not well
      understood. Presently, we investigated the acute (24 hours) effects of
      intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity,
      oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney,
      and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the
      lung, liver, kidney, and brain, but was not changed in the heart. Similarly,
      superoxide dismutase and catalase activities were significantly affected by SiNPs
      in all organs studied. While the concentration of tumor necrosis factor alpha was
      insignificantly increased in the liver and brain, its increase was statistically
      significant in the lung, heart, and kidney. SiNPs induced a significant elevation
      in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver,
      and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed
      by comet assay, in all the organs studied. SiNPs caused leukocytosis and
      increased the plasma activities of lactate dehydrogenase, creatine kinase,
      alanine aminotranferase, and aspartate aminotransferase. These results indicate
      that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and
      DNA damage in several major organs, and highlight the need for thorough
      evaluation of SiNPs before they can be safely used in human beings. 

PMID- 27022260
TI  - Effects of nanoparticle size on antitumor activity of 10-hydroxycamptothecin
      conjugated gold nanoparticles: in vitro and in vivo studies.
AB  - Gold nanoparticles (AuNPs) have emerged as a promising anticancer drug delivery
      scaffold. However, some controversial points still require further investigation
      before clinical use. A complete understanding of how animal cells interact with
      drug-conjugated AuNPs of well-defined sizes remains poorly understood. In this
      study, we prepared a series of 10-hydroxycamptothecin (HCPT)-AuNP conjugates of
      different sizes and compared their cytotoxic effect in vitro and antitumor effect
      in vivo. Transmission electron micrographs showed that the NPs had a round,
      regular shape with a mean diameter of ~10, 25, and 50 nm. An in vitro drug
      release study showed that HCPT was continuously released for 120 hours. HCPT
      AuNPs showed greater cytotoxic effects on the MDA-MB-231 cell line compared with
      an equal dose of free HCPT. Notably, HCPT-AuNPs of an average diameter of 50 nm
      (HCPT-AuNPs-50) had the greatest effect. Furthermore, administration of HCPT
      AuNPs-50 showed the most tumor-suppressing activity against MDA-MB-231 tumor in
      mice among all treatment groups. The results indicate that AuNPs not only act as
      a carrier but also play an active role in mediating biological effects. This work
      gives important insights into the design of nanoscale delivery and therapeutic
      systems. 

PMID- 27022261
TI  - A bio-artificial poly([D,L]-lactide-co-glycolide) drug-eluting nanofibrous
      periosteum for segmental long bone open fractures with significant periosteal
      stripping injuries.
AB  - Biodegradable poly([D,L]-lactide-co-glycolide) (PLGA) nanofibrous membrane
      embedded with two drug-to-polymer weight ratios, namely 1:3 and 1:6, which
      comprised PLGA 180 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg,
      and PLGA 360 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg,
      respectively, was produced as an artificial periosteum in the treatment of
      segmental femoral fractures. The nanofibrous membrane's drug release behavior was
      assessed in vitro using high-performance liquid chromatography and the disk
      diffusion method. A femoral segmental fracture model with intramedullary
      Kirschner-wire fixation was established for the in vivo rabbit activity study.
      Twenty-four rabbits were divided into two groups. Twelve rabbits in group A
      underwent femoral fracture fixation only, and 12 rabbits in group B underwent
      femoral fracture fixation and were administered the drug-loaded nanofibers.
      Radiographs obtained at 2, 6, and 12 weeks postoperatively were used to assess
      the bone unions. The total activity counts in animal behavior cages were also
      examined to evaluate the clinical performance of the rabbits. After the animals
      were euthanized, both femoral shafts were harvested and assessed for their torque
      strengths and toughness. The daily in vitro release curve for lidocaine showed
      that the nanofibers eluted effective levels of lidocaine for longer than 3 weeks.
      The bioactivity studies of vancomycin and ceftazidime showed that both
      antibiotics had effective and sustained bactericidal capacities for over 30 days.
      The findings from the in vivo animal activity study suggested that the rabbits
      with the artificial drug-eluting periosteum exhibited statistically increased
      levels of activity and better clinical performance outcomes compared with the
      rabbits without the artificial periosteum. In conclusion, this artificial drug
      eluting periosteum may eventually be used for the treatment of open fractures.

PMID- 27022262
TI  - Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single
      chain antibody.
AB  - Therapy of melanoma using T-cells with genetically introduced T-cell receptors
      (TCRs) directed against a tumor-selective cancer testis antigen (CTA) NY-ESO1
      demonstrated clear antitumor responses in patients without side effects. Here, we
      exploited the concept of TCR-mediated targeting through introduction of single
      chain variable fragment (scFv) antibodies that mimic TCRs in binding major
      histocompatibility complex-restricted CTA. We produced scFv antibodies directed
      against Melanoma AntiGEn A1 (MAGE A1) presented by human leukocyte antigen A1
      (HLA-A1), in short M1/A1, and coupled these TCR-like antibodies to liposomes to
      achieve specific melanoma targeting. Two anti-M1/A1 antibodies with different
      ligand-binding affinities were derived from a phage-display library and
      reformatted into scFvs with an added cysteine at their carboxyl termini. Protein
      production conditions, ie, bacterial strain, temperature, time, and compartments,
      were optimized, and following production, scFv proteins were purified by
      immobilized metal ion affinity chromatography. Batches of pure scFvs were
      validated for specific binding to M1/A1-positive B-cells by flow cytometry.
      Coupling of scFvs to liposomes was conducted by employing different conditions,
      and an optimized procedure was achieved. In vitro experiments with
      immunoliposomes demonstrated binding of M1/A1-positive B-cells as well as M1/A1
      positive melanoma cells and internalization by these cells using flow cytometry
      and confocal microscopy. Notably, the scFv with nonenhanced affinity of M1/A1,
      but not the one with enhanced affinity, was exclusively bound to and internalized
      by melanoma tumor cells expressing M1/A1. Taken together, antigen-mediated
      targeting of tumor cells as well as promoting internalization of nanoparticles by
      these tumor cells is mediated by TCR-like scFv and can contribute to melanoma
      specific targeting. 

PMID- 27022263
TI  - Antimicrobial performance of mesoporous titania thin films: role of pore size,
      hydrophobicity, and antibiotic release.
AB  - Implant-associated infections are undesirable complications that might arise
      after implant surgery. If the infection is not prevented, it can lead to
      tremendous cost, trauma, and even life threatening conditions for the patient.
      Development of an implant coating loaded with antimicrobial substances would be
      an effective way to improve the success rate of implants. In this study, the in
      vitro efficacy of mesoporous titania thin films used as a novel antimicrobial
      release coating was evaluated. Mesoporous titania thin films with pore diameters
      of 4, 6, and 7 nm were synthesized using the evaporation-induced self-assembly
      method. The films were characterized and loaded with antimicrobial agents,
      including vancomycin, gentamicin, and daptomycin. Staphylococcus aureus and
      Pseudomonas aeruginosa were used to evaluate their effectiveness toward
      inhibiting bacterial colonization. Drug loading and delivery were studied using a
      quartz crystal microbalance with dissipation monitoring, which showed successful
      loading and release of the antibiotics from the surfaces. Results from counting
      bacterial colony-forming units showed reduced bacterial adhesion on the drug
      loaded films. Interestingly, the presence of the pores alone had a desired effect
      on bacterial colonization, which can be attributed to the documented
      nanotopographical effect. In summary, this study provides significant promise for
      the use of mesoporous titania thin films for reducing implant infections. 

PMID- 27022265
TI  - Validity and test-retest reliability of the Persian version of the Montgomery
      Asberg Depression Rating Scale.
AB  - BACKGROUND AND AIMS: The Montgomery-Asberg Depression Rating Scale (MADRS) is an
      expert's rating tool to assess the severity and symptoms of depression. The aim
      of the present two studies was to validate the Persian version of the MADRS and
      determine its test-retest reliability in patients diagnosed with major depressive
      disorders (MDD). METHODS: In study 1, the translated MADRS and the Hamilton
      Depression Rating Scale (HDRS) were applied to 210 patients diagnosed with MDD
      and 100 healthy adults. In study 2, 200 patients diagnosed with MDD were assessed
      with the MADRS in face-to-face interviews. Thereafter, 100 patients were assessed
      3-14 days later, again via face-to-face-interviews, while the other 100 patients
      were assessed 3-14 days later via a telephone interview. RESULTS: Study 1: The
      MADRS and HDRS scores between patients with MDD and healthy controls differed
      significantly. Agreement between scoring of the MADRS and HDRS was high (r=0.95).
      Study 2: The intraclass correlation coefficient (test-retest reliability) was
      r=0.944 for the face-to-face interviews, and r=0.959 for the telephone
      interviews. CONCLUSION: The present data suggest that the Persian MADRS has high
      validity and excellent test-retest reliability over a time interval of 3-14 days,
      irrespective of whether the second assessment was carried out face-to-face or via
      a telephone interview.

PMID- 27022266
TI  - Identification of a seasonal pattern to brain metastases.

PMID- 27022264
TI  - Brain oscillations in bipolar disorder and lithium-induced changes.
AB  - Electroencephalography (EEG) studies in patients with bipolar disorder have
      revealed lower amplitudes in brain oscillations. The aim of this review is to
      describe lithium-induced EEG changes in bipolar disorder and to discuss potential
      underlying factors. A literature survey about lithium-induced EEG changes in
      bipolar disorder was performed. Lithium consistently enhances magnitudes of brain
      oscillations in slow frequencies (delta and theta) in both resting-state EEG
      studies as well as event-related oscillations studies. Enhancement of magnitudes
      of beta oscillations is specific to event-related oscillations. Correlation
      between serum lithium levels and brain oscillations has been reported. Lithium
      induced changes in brain oscillations might correspond to lithium-induced
      alterations in neurotransmitters, signaling cascades, plasticity, brain
      structure, or biophysical properties of lithium. Therefore, lithium-induced
      changes in brain oscillations could be promising biomarkers to assess the
      molecular mechanisms leading to variability in efficacy. Since the variability of
      lithium response in bipolar disorder is due to the genetic differences in the
      mechanisms involving lithium, it would be highly promising to assess the lithium
      induced EEG changes as biomarkers in genetic studies. 

PMID- 27022268
TI  - Comparison of propofol-hydromorphone and propofol-dexmedetomidine in patients
      with intubation after maxillofacial plastic surgery.
AB  - OBJECTIVE: To compare the sedation and analgesic effects between propofol
      hydromorphone and propofol-dexmedetomidine in patients with postoperative
      intubation after maxillofacial plastic surgery. METHODS: Forty-two patients
      undertaking maxillofacial plastic surgery with intubation were randomly assigned
      into propofol plus hydromorphone (P-H) group or propofol plus dexmedetomidine (P
      D) group, receiving intravenous infusion of P-H or P-D, respectively. Cerebral
      state index, Ramsay sedation score, arterial blood gas analysis, and physiology
      indices were recorded before admission (T0), 30 minutes (T1), 1 hour (T2), 2
      hours (T3), 6 hours (T4), and 12 hours after admission (T5) to intensive care
      unit, and 10 minutes after extubation (T6). Blood interleukin-6 was measured with
      enzyme-linked immunosorbent assay. RESULTS: There was no significant difference
      in arterial blood gas analysis, oxygen saturation, mean arterial pressure, and
      respiratory rate between two groups at all time-points (P>0.05). The changes of
      heart rate (at T4, T5, and T6), cerebral state index (T1, T2, T3, T4, and T5),
      and Ramsay score (at T3) in P-H group were significantly different from that in P
      D group (P<0.05). The plasma interleukin-6 at T4 in P-H group was significantly
      lower than that in P-D group (P<0.05). CONCLUSION: The P-H approach takes
      advantages over P-D approach in relieving the pain and discomfort, reducing the
      overstimulation of sympathetic nerve and the stress level, and enhancing the
      tolerance of postoperative intubation after maxillofacial plastic surgery.

PMID- 27022269
TI  - Effect of Ascaris lumbricoides infection on T helper cell type 2 in rural
      Egyptian children.
AB  - Ascaris lumbricoides is a neglected parasite that induces changes in host immune
      response. This study is conducted to define the serum levels of tumor necrosis
      factor alpha (TNF-alpha), interleukin-4 (IL-4), and interleukin-5 (IL-5) in some
      Egyptian children and their relations to intensity of infection, age, and
      ascariasis symptoms. Stool samples were examined using formol-ether concentration
      and Kato-Katz thick smear techniques. Sera of 60 A. lumbricoides-infected
      children and 20 controls were tested by enzyme-linked immunosorbent assay. The
      mean sera concentrations of TNF-alpha, IL-4, and IL-5 were 7.41+/-2.5 pg/mL,
      107.60+/-18.3 pg/mL, and 389.52+/-28.0 pg/mL, respectively. The controls had mean
      serum TNF-alpha 7.10+/-2.4 pg/mL, IL-4 25.49+/-2.6 pg/mL, and IL-5 88.76+/-22.7
      pg/mL. The difference in the concentration of sera cytokines was statistically
      significant for IL-4 and IL-5 (P<0.01) between A. lumbricoides-infected children
      and controls. The intensity of infection correlated positively with IL-4 and IL-5
      at r=0.959 and r=0.919, respectively. The concentrations of IL-4 and IL-5
      correlated positively with the age at r=0.845 and r=0.934, respectively. Asthma
      and gastrointestinal tract upsets were correlated positively with IL-4 and IL-5.
      These data indicate that A. lumbricoides infection in our locality is associated
      with significantly high levels of IL-4 and IL-5. 

PMID- 27022267
TI  - Allergic diseases among children: nutritional prevention and intervention.
AB  - Allergic diseases comprise a genetically heterogeneous group of chronic,
      immunomediated diseases. It has been clearly reported that the prevalence of
      these diseases has been on the rise for the last few decades, but at different
      rates, in various areas of the world. This paper discusses the epidemiology of
      allergic diseases among children and their negative impact on affected patients,
      their families, and societies. These effects include the adverse effects on
      quality of life and economic costs. Medical interest has shifted from tertiary or
      secondary prevention to primary prevention of these chronic diseases among high
      risk infants in early life. Being simple, practical, and cost-effective are
      mandatory features for any candidate methods delivering these strategies. Dietary
      therapy fits this model well, as it is simple, practical, and cost-effective, and
      involves diverse methods. The highest priority strategy is feeding these infants
      breast milk. For those who are not breast-fed, there should be a strategy to
      maintain beneficial gut flora that positively influences intestinal immunity. We
      review the current use of probiotics, prebiotics, and synbiotics, and safety and
      adverse effects. Other dietary modalities of possible potential in achieving this
      primary prevention, such as a Mediterranean diet, use of milk formula with
      modified (hydrolyzed) proteins, and the role of micronutrients, are also
      explored. Breast-feeding is effective in reducing the risk of asthma, allergic
      rhinitis, and atopic eczema among children. In addition, breast milk constitutes
      a major source of support for gut microbe colonization, due to its bifidobacteria
      and galactooligosaccharide content. The literature lacks consensus in
      recommending the addition of probiotics to foods for prevention and treatment of
      allergic diseases, while prebiotics may prove to be effective in reducing atopy
      in healthy children. There is insufficient evidence to support soy formulas or
      amino acid formulas for prevention of allergic disease. A healthy diet, such as
      the Mediterranean diet, may have a protective effect on the development of asthma
      and atopy in children. In children with asthma and allergic diseases, vitamin D
      deficiency correlates strongly with asthma, allergic rhinitis, and wheezing. 

PMID- 27022270
TI  - Erratum: Cone-beam computed tomography study of the root and canal morphology of
      mandibular permanent anterior teeth in a Chongqing population [Corrigendum].
AB  - [This corrects the article on p. 19 in vol. 12, PMID: 26730198.]. 

PMID- 27022271
TI  - Concentrated insulins: the new basal insulins.
AB  - INTRODUCTION: Insulin therapy plays a critical role in the treatment of type 1
      and type 2 diabetes mellitus. However, there is still a need to find basal
      insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally,
      with increasing obesity and insulin resistance, the ability to provide clinically
      necessary high doses of insulin at low volume is also needed. AREAS COVERED: This
      review highlights the published reports of the pharmacokinetic (PK) and
      glucodynamic properties of concentrated insulins: Humulin-R U500, insulin
      degludec U200, and insulin glargine U300, describes the clinical efficacy, risk
      of hypoglycemic, and metabolic changes observed, and finally, discusses
      observations about the complexity of introducing a new generation of concentrated
      insulins to the therapeutic market. CONCLUSION: Humulin-R U500 has a similar
      onset but longer duration of action compared with U100 regular insulin. Insulin
      glargine U300 has differential PK/pharmacodynamic effects when compared with
      insulin glargine U100. In noninferiority studies, glycemic control with degludec
      U200 and glargine U300 is similar to insulin glargine U100 and nocturnal
      hypoglycemia is reduced. Concentrated formulations appear to behave as separate
      molecular entities when compared with earlier U100 insulin analog compounds. In
      the review of available published data, newer concentrated basal insulins may
      offer an advantage in terms of reduced intraindividual variability as well as
      reducing the injection burden in individuals requiring high-dose and large volume
      insulin therapy. Understanding the PK and pharmacodynamic properties of this new
      generation of insulins is critical to safe dosing, dispensing, and
      administration.

PMID- 27022273
TI  - Improving health-related quality of life through an evidence-based obesity
      reduction program: the Healthy Weights Initiative.
AB  - When evaluating any health intervention, it is critical to include the impact of
      the intervention on health-related quality of life (HRQL). Among those who are
      obese, HRQL is often lower than the general population and even more when
      considering obesity-related comorbidities and bodily pain. The objectives of this
      paper were to determine the impact of a multidisciplinary, community-based
      obesity reduction program on HRQL and to determine the independent risk factors
      for lack of improvement from baseline to follow-up. HRQL was measured using the
      Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) at baseline and
      follow-up (24 weeks). To date, 84.5% of those who completed the program had
      improvements in their overall SF-36 score. Significant increases in the mean
      scores on eight dimensions of health were also observed. Lack of improvement was
      independently affected by smoking status (odds ratio 3.75; 95% confidence
      interval 1.44-9.78; P=0.007) and not having a buddy to attend the program (odds
      ratio 3.70; 95% confidence interval 1.28-10.68; P=0.015). Obesity reduction
      programs that target increasing exercise, improving diet, and cognitive
      behavioral therapy can positively impact HRQL in obese adults. Social support has
      a strong role to play in improving outcomes. 

PMID- 27022272
TI  - Atrial fibrillation and silent stroke: links, risks, and challenges.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a projected
      number of 1 million affected subjects in Germany. Changes in age structure of the
      Western population allow for the assumption that the number of concerned people
      is going to be doubled, maybe tripled, by the year 2050. Large epidemiological
      investigations showed that AF leads to a significant increase in mortality and
      morbidity. Approximately one-third of all strokes are caused by AF and, due to
      thromboembolic cause, these strokes are often more severe than those caused by
      other etiologies. Silent brain infarction is defined as the presence of cerebral
      infarction in the absence of corresponding clinical symptomatology. Progress in
      imaging technology simplifies diagnostic procedures of these lesions and leads to
      a large amount of diagnosed lesions, but there is still no final conclusion about
      frequency, risk factors, and clinical relevance of these infarctions. The
      prevalence of silent strokes in patients with AF is higher compared to patients
      without AF, and several studies reported high incidence rates of silent strokes
      after AF ablation procedures. While treatment strategies to prevent clinically
      apparent strokes in patients with AF are well investigated, the role of
      anticoagulatory treatment for prevention of silent infarctions is unclear. This
      paper summarizes developments in diagnosis of silent brain infarction and its
      context to AF.

PMID- 27022274
TI  - Combined action of EGFR tyrosine kinase inhibitors and whole-brain radiotherapy
      on EGFR-mutated non-small-cell lung cancer patients with brain metastasis.
AB  - BACKGROUND: Lung cancer is the most common type of cancer to spread to the brain
      (brain metastasis [BM]). This study assessed the effect of epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in combination with
      whole-brain radiotherapy (WBRT) on EGFR-mutant non-small-cell lung cancer (NSCLC)
      patients with BM. PATIENTS AND METHODS: Thirty-nine patients, who had receieved
      different EGFR TKIs plus 30 Gy WBRT until disease progression, were
      retrospectively analyzed between 2010 and 2014. Treatment response was evaluated
      and survival data were collected and analyzed. RESULTS: Among the 39 patients, 18
      had an EGFR exon 19 deletion and 21 had an EGFR exon 21 point mutation. After
      therapy, 19 (48.7%) patients had complete remission, 12 (30.8%) had partial
      remission, and eight (20.5%) had stable disease in the intracranial lesions.
      Besides, there was no single case of complete remission, 21 (53.8%) had partial
      remission, and 18 (46.2%) had stable disease of the extracranial lesions. The
      median progression-free survival (PFS) of intracranial lesions and extracranial
      lesions was 18 and 12 months, respectively. The median overall survival (OS) was
      26 months. The univariate analysis showed that graded prognostic assessment
      (P=0.006) and Karnofsky Performance Scale (P=0.045) were associated with
      intracranial progression-free survival (iPFS), while recursive partitioning
      analysis (P=0.049) was associated with OS of patients. CONCLUSION: EGFR TKIs plus
      concomitant WBRT controlled intracranial lesions of lung cancer metastasis and
      significantly improved OS of patients. Further studies will be needed to confirm
      whether this combination treatment could be used as a standard therapy for EGFR
      mutated NSCLC patients with BM.

PMID- 27022275
TI  - Screening miRNAs for early diagnosis of colorectal cancer by small RNA deep
      sequencing and evaluation in a Chinese patient population.
AB  - PURPOSE: This study aims to screen microRNAs (miRNAs), for an early diagnosis of
      colorectal cancer, by deep sequencing and evaluation of total miRNAs using
      clinical samples from a Chinese patient population. METHODS: Total small RNAs
      from normal colonic mucosa, colonic adenomas, and colorectal cancer tissues were
      prepared for miRNA analysis by deep sequencing. The sequencing data were then
      analyzed by bioinformatics for candidate diagnostic miRNAs, which were further
      validated for their up- or downregulation status. RESULTS: Comparison of cancer
      tissues with normal mucosa identified 99 upregulated and 90 downregulated miRNAs.
      Comparison of adenomas and normal mucosa found 114 upregulated and 107
      downregulated miRNAs. Comparison of cancer and adenoma tissues found 70
      upregulated and 27 downregulated miRNAs. Selected up- and downregulated miRNAs
      were validated for their expressions in 12 cases of patients with cancer and
      polyps. Specifically, for the upregulated miRNAs, miR-18a-5p and miR-21-3p were
      significantly upregulated in adenomas and cancer tissues, compared with the
      normal mucosa; miR-135b-5p, miR-17-5p, miR-182-5p, miR-200a-5p, and miR-200c-3p
      were significantly upregulated in cancer tissues compared to the normal mucosa,
      but their differential expression was not significant in adenoma tissues when
      compared with the normal mucosa. miR-183-5p and miR-96-5p were significantly
      upregulated in adenoma tissues when compared with normal mucosa, but these
      differences were not significant in cancer tissues when compared to normal
      mucosa. For the downregulated miRNAs, miR-133a-3p was significantly downregulated
      in both adenoma and cancer tissues when compared to normal mucosa; miR-204-5p,
      miR-125b-5p, miR-139-5p, miR-100-5p, and miR-30a-5p were significantly
      downregulated in cancer tissues compared to the normal mucosa, but their
      differential expression was not significant in adenoma tissue compared to normal
      mucosa. CONCLUSION: The findings of this study show that a number of miRNAs might
      be important in the diagnosis and prognosis of colorectal cancer in Chinese
      patients using the method of small RNA deep sequencing. Upregulation of miR-18a
      5p and miR-21-3p or downregulation of miR-133a-3p in adenoma and cancer tissues
      may serve as an index for early screening of colorectal cancer. Other miRNAs,
      such as miR-135b-5p, miR-17-5p, miR-182-5p, miR-200a-5p, miR-200c-3p, miR-183-5p,
      and miR-96-5p, which were either up- or downregulated, in cancer tissues, but not
      in adenoma tissues, have limited significance in early diagnosis. Further study
      is needed to determine a screening index with diagnostic value.

PMID- 27022276
TI  - Efficacy and safety of vascular endothelial growth factor receptor tyrosine
      kinase inhibitors in the treatment of advanced thyroid cancer: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: We performed a systematic review and meta-analysis to determine the
      efficacy and safety of the US Food and Drug Administration approved vascular
      endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in the
      treatment of advanced thyroid cancer. PATIENTS AND METHODS: We included
      prospective randomized controlled trials that compared VEGFR-TKIs with placebo
      for advanced thyroid cancer. The endpoints included safety (fatal adverse events
      [FAEs], treatment discontinuation, and any severe [grade 3 or 4] adverse events
      [AEs]) and efficacy (objective response rate, progression-free survival, and
      overall survival). The pooled relative risk (RR) or hazard ratio (HR) was
      calculated by using either random-effects or fixed-effects models according to
      the heterogeneity of included studies. RESULTS: A total of 1,614 advanced thyroid
      cancer patients from five randomized controlled trials were identified for
      analysis. Compared with placebo alone, VEGFR-TKIs significantly increased the
      risk of treatment discontinuation (RR: 3.80, 95% confidence interval [CI]: 2.56
      5.65, P<0.001) and any severe AEs (RR: 2.63, 95% CI: 1.72-4.03, P<0.001), but not
      of FAEs (RR: 1.24, 95% CI: 0.65-2.39, P=0.52). The use of VEGFR-TKIs in advanced
      thyroid cancer was associated with a significant improvement in objective
      response rate (RR: 8.73, 95% CI: 1.72-44.4, P=0.009) and progression-free
      survival (HR: 0.41, 95% CI: 0.27-0.61, P<0.001), with a tendency to improve
      overall survival (HR: 0.83, 95% CI: 0.68-1.01, P=0.06). CONCLUSION: The use of
      small-molecule VEGFR-TKIs in advanced thyroid cancer did significantly increase
      the risk of treatment discontinuation and any severe AEs, but not of FAEs,
      compared with placebo alone. It is important for physicians to weigh the risk of
      toxicities as well as the potential survival benefits associated with VEGFR-TKI
      treatment in advanced thyroid cancer patients.

PMID- 27022277
TI  - The evaluation of the association between the metabolic syndrome and tumor grade
      and stage of bladder cancer in a Chinese population.
AB  - OBJECTIVE: The objective of this article was to summarize the relationship
      between some components of metabolic syndrome (MetS) and the histopathologic
      findings in bladder cancer in a Chinese population. METHODS: We retrospectively
      analyzed data of 323 patients from the Department of Urology, Second Hospital of
      Tianjin Medical University between January 2012 and January 2014. All the
      patients were diagnosed with bladder cancer for the first time. Age, height,
      weight, histologic stage, grade, the presence of hypertension, diabetes mellitus,
      and body mass index were evaluated. The 2009 American Joint Committee on Cancer
      TNM staging system was used, with Ta and T1 tumors accepted as lower stage and
      T2, T3, and T4 tumors as higher stage bladder cancers. Also, pathologists
      assigned tumor grade according to the 1973 World Health Organization grading
      system. Noninvasive papillary urothelial neoplasms of low malignant potential
      were regarded as low grade. Analyses were completed using chi-square tests and
      logistic regression analysis. RESULTS: Of the 323 patients, 164 had hypertension,
      151 had diabetes mellitus, and 213 had a body mass index >=25 kg/m(2). MetS was
      significantly associated with histologic grade (P<0.001) and stage (P=0.006) of
      bladder cancer. Adjusted for age in binary logistic regression analysis, the
      presence of MetS predicts the risk of higher T stage (odds ratio =4.029, P<0.001)
      and grade (odds ratio =3.870, P<0.001) of bladder cancer. CONCLUSION: The
      patients with MetS in the People's Republic of China were found to have
      statistically significant higher T stage and grade of bladder cancer.

PMID- 27022278
TI  - Profile of farletuzumab and its potential in the treatment of solid tumors.
AB  - Folate receptor (FR) alpha expression in normal tissues is restricted to a
      subpopulation of epithelial cells. In contrast, FRalpha is overexpressed in
      epithelial ovarian cancer (EOC) and non-small-cell lung carcinoma. Therefore,
      FRalpha is considered a promising therapeutic target for EOC and non-small-cell
      lung carcinoma. Farletuzumab (MORAb-003) is a humanized monoclonal antibody of
      immunoglobulin G subtype 1 kappa, targeting human FRalpha. To date, Phase I/II
      clinical trials have clearly demonstrated the feasibility and safety of
      farletuzumab as a treatment option against solid tumors. However, in Phase III
      clinical trial that was conducted to verify the combined effect of paclitaxel
      carboplatin combination therapy and farletuzumab for patients with recurrent EOC,
      improvement in progression-free survival was not statistically significant. This
      result might be owing to the fact that the eligibility criteria for these studies
      did not include FRalpha expression. The significance of FRalpha as a
      predictive/prognostic biomarker remains unclear. In addition, there is currently
      no established biomarker to predict the response and toxicities among patients
      receiving farletuzumab therapy. Furthermore, the primary mechanism of action of
      farletuzumab has not yet been identified. Therefore, further research to identify
      the mechanism of farletuzumab in tumor suppression is necessary to clarify the
      full potential of this chemotherapeutic agent. 

PMID- 27022279
TI  - The role of semaphorin 4D as a potential biomarker for antiangiogenic therapy in
      colorectal cancer.
AB  - BACKGROUND: Semaphorin 4D (Sema4D) belongs to the class IV semaphorins, and
      accumulating evidence has indicated that its elevated level may be one strategy
      by which tumors evade current anti-angiogenic therapies. The biological roles of
      Sema4D in colorectal cancer (CRC), however, remain largely undefined. This study
      was designed to investigate the effects of Sema4D on tumor angiogenesis and
      growth in CRC, especially in different vascular endothelial growth factor (VEGF)
      backgrounds. METHODS: The expression of Sema4D in human CRC was evaluated by
      immunohistochemical analysis of tumors and their matching normal control tissues.
      The expression level of Sema4D and VEGF was investigated in different CRC cell
      lines. To evaluate the contributions of Sema4D to tumor-induced angiogenesis, two
      CRC cell lines with opposite VEGF backgrounds were infected with lentiviruses
      expressing Sema4D or Sema4D short hairpin RNA, followed by in vitro migration and
      in vivo tumor angiogenic assays. RESULTS: Immunohistochemical analysis of human
      CRC revealed high levels of Sema4D in a cell surface pattern. In all, 84.85% of
      CRC samples analyzed exhibited moderate to strong Sema4D expression. The positive
      ratios of Sema4D staining for well, moderately, and poorly differentiated cancers
      were 71.43%, 96.67%, and 77.27%, respectively. Sema4D is highly expressed in five
      different CRC cell lines, while VEGF expression level varies among these cell
      lines. HCT-116 showed the lowest VEGF level, while Caco-2 showed the maximum VEGF
      level. In vitro migration results show that regardless of cell type and VEGF
      background, Sema4D showed an enhanced in vitro proangiogenic effect to induce the
      migration of human umbilical vein endothelial cells. Finally, in vivo tumor
      angiogenic assays demonstrated that Sema4D alone can elicit a significant
      angiogenic response to promote tumor growth independently of VEGF. CONCLUSION:
      Targeting Sema4D might serve as a parallel option for antiangiogenic therapy for
      CRC, particularly when traditional anti-VEGF therapies fail or tumors develop
      resistance to strategies targeting a single angiogenic signaling pathway.

PMID- 27022281
TI  - Integrating subpathway analysis to identify candidate agents for hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second most common cause of cancer
      associated death worldwide, characterized by a high invasiveness and resistance
      to normal anticancer treatments. The need to develop new therapeutic agents for
      HCC is urgent. Here, we developed a bioinformatics method to identify potential
      novel drugs for HCC by integrating HCC-related and drug-affected subpathways. By
      using the RNA-seq data from the TCGA (The Cancer Genome Atlas) database, we first
      identified 1,763 differentially expressed genes between HCC and normal samples.
      Next, we identified 104 significant HCC-related subpathways. We also identified
      the subpathways associated with small molecular drugs in the CMap database.
      Finally, by integrating HCC-related and drug-affected subpathways, we identified
      40 novel small molecular drugs capable of targeting these HCC-involved
      subpathways. In addition to previously reported agents (ie, calmidazolium), our
      method also identified potentially novel agents for targeting HCC. We
      experimentally verified that one of these novel agents, prenylamine, induced HCC
      cell apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide, an acridine orange/ethidium bromide stain, and electron microscopy. In
      addition, we found that prenylamine not only affected several classic apoptosis
      related proteins, including Bax, Bcl-2, and cytochrome c, but also increased
      caspase-3 activity. These candidate small molecular drugs identified by us may
      provide insights into novel therapeutic approaches for HCC. 

PMID- 27022280
TI  - Combination of vatalanib and a 20-HETE synthesis inhibitor results in decreased
      tumor growth in an animal model of human glioma.
AB  - BACKGROUND: Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic
      treatments, such as vatalanib, have been added as an adjuvant to control
      angiogenesis and tumor growth. However, evidence of progressive tumor growth and
      resistance to antiangiogenic treatment has been observed. To counter the unwanted
      effect of vatalanib on GBM growth, we have added a new agent known as N-hydroxy
      N'-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor
      of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. The aims of the studies
      were to determine 1) whether the addition of HET0016 can attenuate the unwanted
      effect of vatalanib on tumor growth and 2) whether the treatment schedule would
      have a crucial impact on controlling GBM. METHODS: U251 human glioma cells
      (4*10(5)) were implanted orthotopically. Two different treatment schedules were
      investigated. Treatment starting on day 8 (8-21 days treatment) of the tumor
      implantation was to mimic treatment following detection of tumor, where tumor
      would have hypoxic microenvironment and well-developed neovascularization. Drug
      treatment starting on the same day of tumor implantation (0-21 days treatment)
      was to mimic cases following radiation therapy or surgery. There were four
      different treatment groups: vehicle, vatalanib (oral treatment 50 mg/kg/d),
      HET0016 (intraperitoneal treatment 10 mg/kg/d), and combined (vatalanib and
      HET0016). Following scheduled treatments, all animals underwent magnetic
      resonance imaging on day 22, followed by euthanasia. Brain specimens were equally
      divided for immunohistochemistry and protein array analysis. RESULTS: Our results
      demonstrated a trend that HET0016, alone or in combination with vatalanib, is
      capable of controlling the tumor growth compared with that of vatalanib alone,
      indicating attenuation of the unwanted effect of vatalanib. When both vatalanib
      and HET0016 were administered together on the day of the tumor implantation (0-21
      days treatment), tumor volume, tumor blood volume, permeability, extravascular
      and extracellular space volume, tumor cell proliferation, and cell migration were
      decreased compared with that of the vehicle-treated group. CONCLUSION: HET0016 is
      capable of controlling tumor growth and migration, but these effects are
      dependent on the timing of drug administration. The addition of HET0016 to
      vatalanib may attenuate the unwanted effect of vatalanib.

PMID- 27022282
TI  - The relationship between apolipoprotein E gene epsilon2/epsilon3/epsilon4
      polymorphism and breast cancer risk: a systematic review and meta-analysis.
AB  - OBJECTIVE: We conducted a systematic review and meta-analysis aiming to assess
      the relationship between apolipoprotein E (APOE) gene epsilon2/epsilon3/epsilon4
      polymorphism and breast cancer risk. METHODS: Yun-Long Liu and Hao-Min Zhang
      independently completed literature retrieval and data collection, and statistical
      analyses were performed by Stata. Individual odds ratio (OR) and 95% confidence
      interval (CI) were pooled in a random-effects model using the DerSimonian-Laird
      method. Heterogeneity was evaluated by I (2) statistic at a significance level of
      50%. Publication bias was assessed by Egger's test. RESULTS: Eleven articles
      including 2,074 breast cancer patients and 2,372 controls were summarized. Using
      the most common allele epsilon3 as a reference, the epsilon2 (OR =0.87, 95% CI
      =0.72-1.05, P=0.154, I (2)=0.0%) and epsilon4 (OR =1.07, 95% CI =0.80-1.42,
      P=0.654, I (2)=71.8%) alleles were not found to be significantly associated with
      breast cancer risk in the overall analyses. Subgroup analyses revealed that the
      comparison of allele epsilon4 with epsilon3 was significant in Asians (OR =1.58,
      95% CI =1.17-6.32, P=0.003, I (2)=12.1%) and in studies that used the restriction
      fragment length polymorphism (RFLP) genotyping method (OR =1.27; 95% CI =1.01
      1.61, P=0.045, I (2)=34.3%), and was marginally significant in hospital-based
      studies (OR =1.33; 95% CI =0.98-1.79, P=0.065, I (2)=30.2%), without
      heterogeneity. Moreover, the presence of the epsilon2 allele was significantly
      associated with breast cancer in small studies (total sample size <500) (OR
      =0.73, 95% CI =0.54-1.00, P=0.052, I (2)=0.0%) without heterogeneity. The Egger's
      test indicated low probabilities of publication bias. CONCLUSION: We observed a
      significant association between APOE gene epsilon4 allele and breast cancer risk
      in Asian populations. Moreover, the findings of our subgroup analyses suggest
      that source of controls, genotyping platform, and sample size might be the
      potential causes of heterogeneity.

PMID- 27022283
TI  - Circulating interleukin-10 levels and human papilloma virus and Epstein-Barr
      virus-associated cancers: evidence from a Mendelian randomization meta-analysis
      based on 11,170 subjects.
AB  - Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that
      determines antiviral immune response and is related to virus-associated cancers.
      However, whether genetically elevated circulating IL-10 levels are associated
      with the risk of human papilloma virus and Epstein-Barr virus-associated cancers
      (HEACs) is still unclear. Mendelian randomization method was implemented to meta
      analyze available observational studies by employing IL-10 three variants (
      592C>A, -819C>T, and -1082A>G) as instruments. A total of 24 articles
      encompassing 11,170 subjects were ultimately eligible for the meta-analysis.
      Overall, there was a significant association between IL-10 promoter variant 
      1082A>G and HEACs under allelic and dominant models (both P<0.01). Subgroup
      analysis by cancer type indicated that the risk estimate of -1082A>G was
      significant for nasopharyngeal cancer under allelic, homozygous genotypic and
      dominant models (all P<0.001). Moreover by ethnicity, carriers of -1082G allele
      had a 74% increased risk for nasopharyngeal cancer in Asians under dominant model
      (odds ratio [OR] =1.737; 95% confidence interval [CI]: 1.280-2.358; P<0.001). In
      further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment
      in IL-10 levels was 1.14 (95% CI: 1.01-16.99) in HEACs. Our findings provided
      strong evidence for a critical role of genetically elevated circulating IL-10
      levels in the development of HEACs, especially in Asian population and for
      nasopharyngeal cancer. 

PMID- 27022284
TI  - Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis.
AB  - PURPOSE: Several molecular epidemiological studies have investigated the
      association between OPN rs11730582 C>T polymorphism and cancer risk, but the
      results are inconsistent. Hence, a meta-analysis was conducted to determine the
      association of this polymorphism with cancer risk. MATERIALS AND METHODS: The
      related articles were searched in PubMed, Embase, and Chinese National Knowledge
      Infrastructure databases. Pooled odds ratios and 95% confidence intervals were
      calculated to evaluate the strength of the associations. A random-effects model
      or fixed-effects model was employed depending on the heterogeneity. RESULTS: A
      total of ten case-control studies involving 2,749 cancer cases and 3,398 controls
      were included in the meta-analysis. In overall analysis, OPN rs11730582 C.T
      polymorphism was not associated with cancer risk. In a stratified analysis by
      cancer type, no significant association was found between OPN rs11730582 C>T
      polymorphism and the risk of glioma, gastric cancer, and other cancers.
      CONCLUSION: This meta-analysis suggests that OPN rs11730582 C.T polymorphism is
      not associated with cancer susceptibility.

PMID- 27022286
TI  - Diagnostic value of two-dimensional shear wave elastography in papillary thyroid
      microcarcinoma.
AB  - OBJECTIVE: The purpose of this study was to evaluate the predictability of two
      dimensional shear wave elastography (2D-SWE) for papillary thyroid microcarcinoma
      (PTMC). MATERIALS AND METHODS: One hundred and eighteen patients with 137 thyroid
      nodules (46 benign nodules, 91 malignant nodules) were included in this study who
      received conventional ultrasound (US) and 2D-SWE before fine-needle aspiration or
      surgery. The diagnostic performance was compared between US findings only and the
      combined use of US findings with 2D-SWE, which were correlated with pathology
      results. RESULTS: Receiver-operating characteristic curve analysis was performed
      to assess the diagnostic performance of 2D-SWE. Conventional US findings and 2D
      SWE values were analyzed and compared between benign and malignant thyroid
      nodules. The mean values of SWE_mean, SWE_min, and SWE_max were 46.6+/-16.7,
      26.2+/-9.5, and 73.6+/-18.1 kPa, respectively, in PTMC, which were significantly
      higher than those in benign tumors (27.8+/-12.4, 15.8+/-8.6, and 50.3+/-22.6 kPa,
      P<0.001). The optimal cut-off values of SWE_mean, SWE_min, and SWE_max for
      predicting malignancy were 34.5, 21.8, and 53.2 kPa, respectively. Taller than
      wide, micro-calcification, and SWE_mean were found to be independent risk factors
      for predicting PTMC. The overall sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of combined conventional US
      features with 2D-SWE parameters were 95.7%, 94.5%, 94.9%, 89.8%, and 97.7%,
      respectively; these were superior to those of conventional US (89.1%, 90.1%,
      89.9%, 82.0%, and 93.2%). CONCLUSION: The study indicates that the quantitative
      parameters of 2D-SWE are an independent predictive factor for diagnosing PTMC,
      which could provide valuable information when conventional US cannot give
      determinate results.

PMID- 27022285
TI  - Role of gefitinib in the targeted treatment of non-small-cell lung cancer in
      Chinese patients.
AB  - Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer.
      Conventional treatment options have limited efficacy because most cases are in
      the advanced stage at the time of diagnosis. In recent years, gefitinib, an
      epidermal growth factor receptor tyrosine kinase inhibitor, has shown its good
      antitumor activities in treating NSCLC in a number of studies. This paper reviews
      its role in the targeted treatment of NSCLC in Chinese patients. 

PMID- 27022287
TI  - A prospective comparison of acute intestinal toxicity following whole pelvic
      versus small field intensity-modulated radiotherapy for prostate cancer.
AB  - PURPOSE: To compare the acute intestinal toxicity of whole pelvic (WP) and small
      field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using
      dosimetric and metabolic parameters as well as clinical findings. METHODS:
      Patients who received IMRT in either a definitive or postoperative setting were
      prospectively enrolled. Target volume and organs at risk including intestinal
      cavity (IC) were delineated in every patient by a single physician. The IC volume
      that received a 10-50 Gy dose at 5-Gy intervals (V10-V50) and the percentage of
      irradiated volume as a fraction of total IC volume were calculated. Plasma
      citrulline levels, as an objective biological marker, were checked at three time
      points: baseline and after exposure to 30 Gy and 60 Gy. RESULTS: Of the 41
      patients, only six experienced grade 1 acute intestinal toxicity. Although all
      dose-volume parameters were significantly worse following WP than SF IMRT, there
      was no statistically significant relationship between these dosimetric parameters
      and clinical symptoms. Plasma citrulline levels did not show a serial decrease by
      radiotherapy volume difference (WP versus SF) and were not relevant to the
      irradiated doses. CONCLUSION: Given that WP had comparable acute intestinal
      toxicities to those associated with SF, WP IMRT appears to be a feasible approach
      for the treatment of prostate cancer despite dosimetric disadvantages.

PMID- 27022288
TI  - Metabolism-related enzyme alterations identified by proteomic analysis in human
      renal cell carcinoma.
AB  - The renal cell carcinoma (RCC) is one of the most common types of kidney
      neoplasia in Western countries; it is relatively resistant to conventional
      chemotherapy and radiotherapy. Metabolic disorders have a profound effect on the
      degree of malignancy and treatment resistance of the tumor. However, the
      molecular characteristics related to impaired metabolism leading to the
      initiation of RCC are still not very clear. In this study, two-dimensional
      electrophoresis (2-DE) and mass spectra (MS) technologies were utilized to
      identify the proteins involved in energy metabolism of RCC. A total of 73
      proteins that were differentially expressed in conventional RCC, in comparison
      with the corresponding normal kidney tissues, were identified. Bioinformatics
      analysis has shown that these proteins are involved in glycolysis, urea cycle,
      and the metabolic pathways of pyruvate, propanoate, and arginine/proline. In
      addition, some were also involved in the signaling network of p53 and FAS. These
      results provide some clues for new therapeutic targets and treatment strategies
      of RCC. 

PMID- 27022289
TI  - Association of thymidylate synthase expression and clinical outcomes of gastric
      cancer patients treated with fluoropyrimidine-based chemotherapy: a meta
      analysis.
AB  - PURPOSE: Although several studies have suggested an association between
      thymidylate synthase (TS) expression and outcomes of gastric cancer (GC) patients
      treated with fluoropyrimidine-based chemotherapy (FUC), the predictive value of
      TS for response and survival in this setting is unclear. This meta-analysis aimed
      to estimate prognostic and predictive significance of TS more precisely. METHODS:
      We searched PubMed, Embase, Cochrane Library, and Web of Science databases for
      literature published up to June 2015. Primary outcomes included hazard ratios
      (HRs) for overall survival (OS), and event-free survival (EFS) and odds ratio
      (OR) for chemotherapy response. Fixed- or random-effects models were used to
      calculate pooled HR and OR according to heterogeneity. RESULTS: A total of 2,442
      GC patients in 25 studies met our inclusion criteria. Response rates for FUC were
      significantly lower in patients with high TS expression than in those with low
      expression (OR: 0.43, 95% confidence interval [CI]: 0.22-0.84, P=0.013). High TS
      expression was significantly correlated with unfavorable OS (HR: 1.62, 95% CI:
      1.28-2.05, P<0.001) and EFS (HR: 1.54, 95% CI: 1.22-1.93, P<0.001) in advanced
      disease. However, TS expression was not significantly related to OS (HR: 1.06,
      95% CI: 0.74-1.50, P=0.760) or EFS (HR: 1.16, 95% CI: 0.84-1.61, P=0.374) in the
      adjuvant setting. CONCLUSION: Higher TS expression might predict drug resistance
      and adverse prognosis in patients with advanced GC treated with FUC.

PMID- 27022290
TI  - p53 inhibits the expression of p125 and the methylation of POLD1 gene promoter by
      downregulating the Sp1-induced DNMT1 activities in breast cancer.
AB  - p125 is one of four subunits of human DNA polymerases - DNA Pol delta as well as
      one of p53 target protein encoded by POLD1. However, the function and
      significance of p125 and the role that p53 plays in regulating p125 expression
      are not fully understood in breast cancer. Tissue sections of human breast cancer
      obtained from 70 patients whose median age was 47.6 years (range: 38-69 years)
      with stage II-III breast cancer were studied with normal breast tissue from the
      same patients and two human breast cell lines (MCF-7 and MCF-10A). p53 expression
      levels were reduced, while p125 protein expression was increased in human breast
      cancer tissues and cell line detected by Western blot and quantitative reverse
      transcriptase-polymerase chain reaction. The methylation level of the POLD1 gene
      promoter was greater in breast cancer tissues and cells when compared with normal
      tissues and cells. In MCF-7 cell model, p53 overexpression caused a decrease in
      the level of p125 protein, while the methylation level of the p125 gene promoter
      was also inhibited by p53 overexpression. To further investigate the regulating
      mechanism of p53 on p125 expression, our study focused on DNA methyltransferase 1
      (DNMT1) and transcription factor Sp1. Both DNMT1 and Sp1 protein expression were
      reduced when p53 was overexpressed in MCF-7 cells. The Sp1 binding site appears
      to be important for DNMT1 gene transcription; Sp1 and p53 can bind together,
      which means that DNMT1 gene expression may be downregulated by p53 through
      binding to Sp1. Because DNMT1 methylation level of the p125 gene promoter can
      affect p125 gene transcription, we propose that p53 may indirectly regulate p125
      gene promoter expression through the control of DNMT1 gene transcription. In
      conclusion, the data from this preliminary study have shown that p53 inhibits the
      methylation of p125 gene promoter by downregulating the activities of Sp1 and
      DNMT1 in breast cancer. 

PMID- 27022291
TI  - Impact of the care provided by gynecologic oncologists on outcomes of cervical
      cancer patients treated with radical hysterectomy.
AB  - For many malignant diseases, specialized care has been reported to be associated
      with better outcomes. The purpose of this study is to investigate the influence
      of gynecologic oncologists on treatment outcomes for cervical cancer patients
      treated by radical hysterectomy. Records of patients who received radical
      hysterectomy between January 2005 and June 2010 were reviewed. Perioperative
      morbidity, recurrence-free survival, and cancer-specific survival were assessed.
      Cox regression model was used to evaluate gynecologic oncologists as an
      independent predictor of survival. A total of 839 patients were included. Of
      these patients, 553 were treated by gynecologic oncologists, while 286 were
      treated by other subspecialties. With regard to operative outcomes, significant
      differences in favor of operation by gynecologic oncologists were found in number
      of patients receiving para-aortic node sampling and dissection (P=0.038),
      compliance with surgical guidelines (P=0.003), operative time (P<0.0001),
      estimated blood loss (P<0.0001), transfusion rate (P=0.046), number of removed
      nodes (P=0.033), and incidences of ureteric injury (P=0.027), cystotomy
      (P=0.038), and fistula formation (P=0.002). Patients who were operated on by
      gynecologic oncologists had longer recurrence-free survival (P=0.001; hazard
      ratio [HR] =0.64; 95% confidence interval [CI] [0.48, 0.84]) and cancer-specific
      survival (P=0.005; HR=0.64; 95% CI [0.47, 0.87]), and this association remained
      significant in patients with locally advanced disease. Care by gynecologic
      oncologists was an independent predictor for improved recurrence-free survival
      (P<0.0001; HR=0.57; 95% CI [0.42, 0.76]) and cancer-specific survival (P=0.001;
      HR=0.58; 95% CI [0.42, 0.81]), which was still significant among patients with
      locally advanced cancer. Given the results, we believe for cervical cancer
      patients receiving radical hysterectomy, operation by gynecologic oncologists
      results in significantly improved surgical and survival outcomes. The importance
      of the subspecialty of a gynecologist for cervical cancer patients should be
      addressed in clinical practice, especially for those in developing countries. 

PMID- 27022292
TI  - Quantitative assessment of caveolin-1 G14713A polymorphism and cancer
      susceptibility in the Asian population.
AB  - PURPOSE: The relationship between caveolin-1 (CAV1) G14713A polymorphism and
      cancer susceptibility remains inconclusive. The current meta-analysis was
      performed on the basis of a systematic search in electronic databases for a more
      precise estimation of the associations. METHODS: Odds ratio (OR) with 95%
      confidence interval (CI) was used to estimate the pooled effect. RESULTS: A total
      of 12 studies including 4,994 cases and 5,606 controls were involved in this meta
      analysis. In the overall analysis, CAV1 G14713A polymorphism was significantly
      associated with an increased risk of cancer (A vs G: OR =1.77, 95% CI: 1.49-2.10,
      P het<0.01; [AA + AG] vs GG: OR =2.03, 95% CI: 1.64-2.53, P het<0.01; AA vs [AG +
      GG]: OR =1.72, 95% CI: 1.40-2.12, P het<0.01; AA vs GG: OR =2.24, 95% CI: 1.69
      2.98, P het<0.01; AG vs GG: OR =1.98, 95% CI: 1.62-2.41, P het<0.01). Subgroup
      analysis by cancer type showed that CAV1 G14713A polymorphism was associated with
      an increased risk of digestive system cancer and other cancer types. CONCLUSION:
      Our findings suggest that CAV1 G14713A polymorphisms may modify the risk of
      cancer, especially digestive system cancer. However, further well-designed
      studies are warranted to validate this association.

PMID- 27022293
TI  - Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical
      advances.
AB  - Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower
      and upper airways, respectively. Molecular and cellular studies indicate that
      these diseases can be categorized into unique endotypes, which have therapeutic
      implications. One such endotype is aspirin-exacerbated respiratory disease
      (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti
      inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique
      pathophysiological features that distinguish it from aspirin-tolerant asthma and
      other forms of chronic rhinosinusitis. This review details molecular and cellular
      features of AERD and highlights current and future therapies that are based on
      these insights. 

PMID- 27022295
TI  - Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification
      of six novel cystic fibrosis-causing genetic variants.
AB  - The mutations in the CFTR gene found in patients with cystic fibrosis (CF) have
      geographic differences, but there are scant data on their prevalence in
      Venezuelan patients. This study determined the frequency of common CFTR gene
      mutations in a group of Venezuelan patients with CF. The 27 exons of the CFTR
      gene from 110 Venezuelan patients in the National CF Program were amplified and
      sequenced. A total of 36 different mutations were identified, seven with
      frequencies greater than 1%: p.Phe508del (27.27%), p.Gly542* (3.18%), c.2988+1G>A
      (3.18%), p.Arg334Trp (1.36%), p.Arg1162* (1.36%), c.1-8G>C (1.36%), and
      p.[Gly628Arg;Ser1235Arg](1.36). In 40% of patients, all with a clinical diagnosis
      of CF, no mutations were found. This report represents the largest cohort of
      Venezuelan patients with CF ever examined, and includes a wider mutation panel
      than has been previously studied in this population. Mutations common in Southern
      European populations predominate, and several new mutations were discovered, but
      no mutations were found in 40% of the cohort. 

PMID- 27022294
TI  - A systematic review of disease-related stigmatization in patients living with
      inflammatory bowel disease.
AB  - Chronic illness stigma is a global public health issue. Most widely studied in
      HIV/AIDS and mental illness, stigmatization of patients living with inflammatory
      bowel disease (IBD), chronic autoimmune conditions affecting the digestive tract,
      has garnered increasing attention in recent years. In this paper, we
      systematically review the scientific literature on stigma as it relates to IBD
      across its three domains: perception, internalization, and discrimination
      experiences. We aim to document the current state of research, identify gaps in
      our knowledge, recognize unique challenges that IBD patients may face as they
      relate to stigmatization, and offer suggestions for future research directions.
      Based on the current review, patients living with IBD may encounter
      stigmatization and this may, in turn, impact several patient outcomes including
      quality of life, psychological functioning, and treatment adherence. Significant
      gaps exist related to the understanding of IBD stigma, providing opportunity for
      future studies to address this important public health issue. 

PMID- 27022297
TI  - Efficacy and safety of iron isomaltoside (Monofer((r))) in the management of
      patients with iron deficiency anemia.
AB  - New intravenous (IV) iron preparations should ideally be capable of delivering a
      wide dosing range to allow iron correction in a single or low number of visits, a
      rapid infusion (doses up to 1,000 mg must be administered over more than 15
      minutes and doses exceeding 1,000 mg must be administered over 30 minutes or
      more), and minimal potential side effects including low catalytic/labile iron
      release with minimal risk of anaphylaxis. Furthermore, they should be convenient
      for the patient and health-care professional, and cost effective for the health
      care system. The intention behind the development of iron isomaltoside
      (Monofer((r))) was to fulfill these requirements. Iron isomaltoside has been
      shown to be effective in treating iron deficiency anemia across multiple
      therapeutic patient groups and compared to placebo, IV iron sucrose, and oral
      iron. Iron isomaltoside consists of iron and a carbohydrate moiety where the iron
      is tightly bound in a matrix structure. It has a low immunogenic potential, a low
      potential to release labile iron, and does not appear to be associated with
      clinically significant hypophosphatemia. Due to the structure of iron
      isomaltoside, it can be administered in high doses with a maximum single dosage
      of 20 mg/kg body weight. Clinical trials and observational studies of iron
      isomaltoside show that it is an effective and well-tolerated treatment of anemia
      across different therapeutic areas with a favorable safety profile. 

PMID- 27022298
TI  - Effect of verbal persuasion on self-efficacy for pain-related diagnostic sensory
      testing in individuals with chronic neck pain and healthy controls - a
      randomized, controlled trial.
AB  - The aim of this study was to investigate the differences in cold pain threshold
      (CTh), pressure pain threshold (PPT), cold pain tolerance (CPTo) tests, and the
      level of self-efficacy when self-efficacy for diagnostic sensory testing was
      manipulated by verbal persuasion before a testing situation in persons with neck
      pain and in healthy controls. A randomized experimental design was used. Twenty
      one healthy volunteers and 22 individuals with either traumatic or nontraumatic
      chronic neck pain were recruited to participate in the study. The intervention
      consisted of two experimental verbal persuasion conditions: Increase self
      efficacy and Decrease self-efficacy. The PPT was measured using a pressure
      algometer, the CTh was measured using a thermo test system, and CPTo was measured
      by submerging the participant's hand in ice water up to the elbow joint. On three
      occasions, the participants reported their self-efficacy level in performing the
      sensory tests. In the chronic neck pain group, there were no differences in pain
      threshold or tolerance. There was a difference in the self-efficacy level after
      verbal persuasion between the experimental conditions. In the healthy control
      group, the CThs increased following the condition that aimed to increase self
      efficacy. No other differences were observed in the healthy controls. A short
      verbal persuasion in the form of manipulative instructions seems to have a
      marginal effect on the individual's self-efficacy levels in the chronic neck pain
      group and a slight influence on the results of sensory testing in healthy
      controls. 

PMID- 27022296
TI  - Renal cell carcinoma: links and risks.
AB  - This review provides an overview of the incidence of renal cell carcinoma (RCC)
      and a summary of the most commonly associated risk factors. A literature review
      was performed with a focus on recent studies with a high level of evidence (large
      prospective cohort studies and meta-analyses). The incidence rate of RCC varies
      globally, with the rate rising rapidly in more developed regions, demonstrating
      the effects of increased use of diagnostic imaging and prevalence of modifiable
      risk factors. Based on the current evidence, cigarette smoking, obesity, and
      hypertension are the most well-established risk factors for sporadic RCC
      worldwide. Acquired cystic kidney disease is also a significant risk factor,
      specifically in dialysis patients. There is increasing evidence for an inverse
      association between RCC risk and moderate alcohol consumption. Certain analgesics
      and occupational exposure have been linked to an increased risk of RCC, although
      data are limited. Diets rich in fruits and vegetables may provide a protective
      effect. 

PMID- 27022299
TI  - Acetaminophen for analgesia following pyloromyotomy: does the route of
      administration make a difference?
AB  - BACKGROUND: During the perioperative care of infants with hypertrophic pyloric
      stenosis, an opioid-sparing technique is often advocated due to concerns such as
      postoperative hypoventilation and apnea. Although the rectal administration of
      acetaminophen is commonly employed, an intravenous (IV) preparation is also
      currently available, but only limited data are available regarding IV
      acetaminophen use for infants undergoing pyloromyotomy. The objective of the
      current study was to compare the efficacy of IV and rectal acetaminophen for
      postoperative analgesia in infants undergoing laparoscopic pyloromyotomy.
      METHODS: A retrospective review of the use of IV and rectal acetaminophen in
      infants undergoing laparoscopic pyloromyotomy was performed. The efficacy was
      assessed by evaluating the perioperative need for supplemental analgesic agents,
      postoperative pain scores, tracheal extubation time, time in the postanesthesia
      care unit, time to oral feeding, and time to hospital discharge. RESULTS: The
      study cohort included 68 patients, of whom 34 patients received IV acetaminophen
      and 34 received rectal acetaminophen. All patients also received local
      infiltration of the surgical site with 0.25% bupivacaine. No intraoperative
      opioids were administered. There was no difference between the two groups with
      regard to postoperative pain scores, need for supplemental analgesic agents, time
      in the postanesthesia care unit, or time in the hospital. There was no difference
      in the number of children who tolerated oral feeds on the day of surgery or in
      postoperative complications. CONCLUSION: Our preliminary data suggest that there
      is no clinical difference or advantage with the use of IV versus rectal
      acetaminophen in infants undergoing laparoscopic pyloromyotomy.

PMID- 27022300
TI  - Opioids for chronic pain: a knowledge assessment of nonpain specialty providers.
AB  - INTRODUCTION: Although the majority of opioids in the US are prescribed by
      nonpain specialists, these providers often report inadequate training in chronic
      pain management and opioid prescribing. The extent of health care providers'
      knowledge of opioid prescribing for chronic pain has not been well established.
      The purpose of this study was to assess knowledge about the use of opioids for
      chronic pain among health care providers seeking pain-focused continuing medical
      education. MATERIALS AND METHODS: The study participants (n=131) were recruited
      at a pain-focused continuing medical education conference for nonpain
      specialists. Upon commencement of the conference, the KnowPain-50 survey was
      completed. The survey comprised 50 questions, and 18 questions were related to
      opioid management. The focus of each opioid question was further categorized as
      either medicolegal (n=7) or clinical (n=11). RESULTS: The majority of study
      participants were male physicians with a mean age of 51.8 years. The proportion
      of correct responses to the 50-item survey was 72%. The proportion of correct
      responses to the 32 nonopioid questions was 74%, and the proportion of correct
      responses to the 18 opioid questions was 69% (P<0.001). Similarly, the proportion
      of correct responses to the seven medicolegal opioid questions was 74%, and the
      proportion of correct responses to the eleven clinical opioid questions was 67%
      (P<0.001). CONCLUSION: Health care providers demonstrated gaps in knowledge about
      the use of opioids for chronic pain. Lower scores on clinically based opioid
      questions may indicate an opportunity to provide focused educational content
      about this area of practice. This information could be helpful in designing
      future educational modules for nonpain providers.

PMID- 27022301
TI  - Identification and prioritization of candidate genes for symptom variability in
      breast cancer survivors based on disease characteristics at the cellular level.
AB  - Research is beginning to suggest that the presence and/or severity of symptoms
      reported by breast cancer survivors may be associated with disease-related
      factors of cancer. In this article, we present a novel approach to the
      identification and prioritization of biologically plausible candidate genes to
      investigate relationships between genomic variation and symptom variability in
      breast cancer survivors. Cognitive dysfunction is utilized as a representative
      breast cancer survivor symptom to elucidate the conceptualization of and
      justification for our cellular, disease-based approach to address symptom
      variability in cancer survivors. Initial candidate gene identification was based
      on genes evaluated as part of multigene expression profiles for breast cancer,
      which are commonly used in the clinical setting to characterize the biology of
      cancer cells for the purpose of describing overall tumor aggressiveness,
      prognostication, and individualization of therapy. A list of genes evaluated
      within five multigene expression profiles for breast cancer was compiled. In
      order to prioritize candidate genes for investigation, genes used in each profile
      were compared for duplication. Twenty-one genes (BAG1, BCL2, BIRC5, CCNB1, CENPA,
      CMC2, DIAPH3, ERBB2, ESR1, GRB7, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR,
      RACGAP1, RFC4, RRM2, and SCUBE2) are utilized in two or more profiles, including
      five genes (CCNB1, CENPA, MELK, MYBL2, and ORC6) used in three profiles. To
      ensure that the parsimonious 21 gene set is representative of the more global
      biological hallmarks of cancer, an Ingenuity Pathway Analysis was conducted.
      Evaluation of genes known to impact pathways involved with cancer development and
      progression provide a means to evaluate the overlap between the biological
      underpinnings of cancer and symptom development within the context of cancer. 

PMID- 27022302
TI  - Astym therapy improves function and range of motion following mastectomy.
AB  - Hypersensitive scar tissue formation along the incision line and drain site is a
      common side effect following mastectomy. If this scar tissue is not addressed, it
      can lead to decreased flexibility and function in the involved upper quadrant.
      Astym((r)) treatment is a new approach to soft tissue injuries, and is evidenced
      in animal studies to promote the healing and regeneration of soft tissues. It has
      also been found to reduce pain and increase function in people with soft tissue
      dysfunction. The aim of Astym treatment is to engage the regenerative mechanisms
      of the body in order to resorb scar tissue, stimulate tissue turnover, and
      regenerate soft tissues. Handheld instrumentation is applied topically to locate
      and treat the underlying dysfunctional soft tissue through specific protocols for
      the application of particular pressures and shear forces. The purpose of this
      study was to examine the effects of Astym treatment on activities of daily living
      in women who had undergone a mastectomy following a diagnosis of breast cancer. A
      quasi-experiment involving 40 women, following a mastectomy, evaluated five
      outcome measures pre- and post-Astym treatment. All five measurement scores:
      Disabilities of the Arm, Shoulder, and Hand Outcome Measure; a clothing
      questionnaire on their ability to wear a bra; Patient-Specific Functional Scale;
      active range of motion of shoulder flexion; and active range of motion of
      abduction were also measured and all demonstrated significant changes. In this
      study, Astym treatment improved active range of motion in the involved quadrant
      and also improved function in patients following a mastectomy. 

PMID- 27022304
TI  - Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose
      combinations for the treatment of HIV-1 infection.
AB  - Atazanavir/cobicistat (ATV/c) and darunavir/cobicistat (DRV/c) are newly approved
      once daily fixed-dose protease inhibitor combinations for the treatment of HIV-1
      infection. Studies in healthy volunteers have established bioequivalence between
      cobicistat and ritonavir as pharmacoenhancers of both atazanavir (ATV) and
      darunavir (DRV). In addition, two randomized clinical trials (one Phase II and
      one Phase III noninferiority trial with a 144-week followup period) demonstrated
      that cobicistat had sustainable and comparable efficacy and safety to ritonavir
      as a pharmacoenhancer of ATV through 144 weeks of treatment in HIV-1-infected
      patients. Furthermore, one Phase III, open-label, single-arm, clinical trial
      reflected virologic and immunologic responses and safety outcomes consistent with
      prior published data for DRV/ritonavir 800/100 mg once daily, supporting the use
      of DRV/c 800/150 mg once daily for future treatment of treatment-naive and 
      experienced HIV-1-infected patients with no DRV resistance-associated mutations.
      Low rates of virologic failure secondary to resistance to antiretroviral regimens
      were present in these clinical studies. Most notable adverse events in the ATV
      studies were hyperbilirubinemia and in the DRV study rash. Small increases in
      serum creatinine and minimally reduced estimated glomerular filtration rate
      Cockcroft-Gault calculation (eGFRCG) were observed in ATV/c and DRV/c clinical
      studies consistent with other studies evaluating
      elvitegravir/cobicistat/tenofovir/emtricitabine for the treatment of HIV-1
      infection. These renal parameter changes occurred acutely in the first few weeks
      and plateaued off for the remaining study periods and are not necessarily
      clinically relevant. Cobicistat has numerous advantages compared to ritonavir
      such as fewer drug-drug interactions, being devoid of anti-HIV-1 activity, as
      well as it has better solubility affording coformulation with other
      antiretrovirals as simplified fixed-dose combinations. Overall, the recent
      approval of ATV/c and DRV/c offers HIV patients opportunities for improved
      adherence to lifelong treatment. Future studies are warranted to determine the
      efficacy and safety of ATV/c and DRV/c in treatment-experienced patients. 

PMID- 27022303
TI  - Strategies to manage patients with dental anxiety and dental phobia: literature
      review.
AB  - Dental anxiety and phobia result in avoidance of dental care. It is a frequently
      encountered problem in dental offices. Formulating acceptable evidence-based
      therapies for such patients is essential, or else they can be a considerable
      source of stress for the dentist. These patients need to be identified at the
      earliest opportunity and their concerns addressed. The initial interaction
      between the dentist and the patient can reveal the presence of anxiety, fear, and
      phobia. In such situations, subjective evaluation by interviews and self
      reporting on fear and anxiety scales and objective assessment of blood pressure,
      pulse rate, pulse oximetry, finger temperature, and galvanic skin response can
      greatly enhance the diagnosis and enable categorization of these individuals as
      mildly, moderately, or highly anxious or dental phobics. Broadly, dental anxiety
      can be managed by psychotherapeutic interventions, pharmacological interventions,
      or a combination of both, depending on the level of dental anxiety, patient
      characteristics, and clinical situations. Psychotherapeutic interventions are
      either behaviorally or cognitively oriented. Pharmacologically, these patients
      can be managed using either sedation or general anesthesia. Behavior-modification
      therapies aim to change unacceptable behaviors through learning, and involve
      muscle relaxation and relaxation breathing, along with guided imagery and
      physiological monitoring using biofeedback, hypnosis, acupuncture, distraction,
      positive reinforcement, stop-signaling, and exposure-based treatments, such as
      systematic desensitization, "tell-show-do", and modeling. Cognitive strategies
      aim to alter and restructure the content of negative cognitions and enhance
      control over the negative thoughts. Cognitive behavior therapy is a combination
      of behavior therapy and cognitive therapy, and is currently the most accepted and
      successful psychological treatment for anxiety and phobia. In certain situations,
      where the patient is not able to respond to and cooperate well with
      psychotherapeutic interventions, is not willing to undergo these types of
      treatment, or is considered dental-phobic, pharmacological therapies such as
      sedation or general anesthesia should be sought. 

PMID- 27022305
TI  - Leg ischemia post-varicocelectomy.
AB  - Varicocelectomy is the most commonly performed operation for the treatment of
      male infertility. Many surgical approaches are used as each of them has
      advantages over the other and is preferred by surgeons. Vascular injury has never
      been reported as a complication of varicocelectomy apart from testicular artery
      injury. We present a 36-year-old male who developed leg ischemia post
      varicocelectomy due to common femoral artery injury. He was successfully treated
      by using a vein graft. 

PMID- 27022306
TI  - The perception of intuition in clinical practice by Iranian critical care nurses:
      a phenomenological study.
AB  - BACKGROUND: Intuition as a way of learning in nursing is applied to decision
      making and judgment in complicated clinical situations. Several studies have been
      conducted on intuition in clinical settings, but comprehension of this concept is
      unclear. Moreover, there is a lack of information about intuition in critical
      care nurses caring for more seriously ill patients. This study aimed to explore
      Iranian critical care nurses' understanding of intuition in clinical practice.
      METHODS: In a descriptive-phenomenological study, 12 nurses employed in critical
      care units of the hospitals affiliated to Kermanshah University of Medical
      Sciences were purposively recruited to the study. A semistructured interview was
      administered, and then written verbatim. The data were managed by MAXQDA 10
      software, and qualitative analysis was undertaken using the seven-stage approach
      of Colaizzi. RESULTS: Of the 12 nurses who participated in the study, 7 (58.3%)
      were female and married, and 10 (88.3%) held a bachelor's degree in nursing. The
      mean and standard deviations of participants' age, job experience, and critical
      care experience were 36.66+/-7.01, 13.75+/-6.82, and 7.66+/-3.36 years,
      respectively. Four main themes and eleven sub-themes were elicited from the
      qualitative analysis; the main themes including "Understanding intuition as a
      feeling", "Understanding intuition as a thought", "Understanding intuition as
      receiving signs", and "Understanding intuition as an alarm". Because they have
      trust in their own intuition, the nurses made further assessments and paid more
      attention to patients. They were also better prepared after receiving intuition
      alarms to perform the appropriate responses, and acting upon the alarms reduced
      the nurses' physical and psychological signs. CONCLUSION: The findings showed how
      intuition was understood by the critical care nurses; therefore, these results
      can be considered to form a theoretical basis for designing other studies.
      Because of the significant role of intuition in enhancing the nursing care of
      critically ill patients, it is suggested that more qualitative, quantitative, and
      trials studies be performed to reinforce intuition in nursing; moreover, to
      incorporate intuition into nursing curriculums, it should be debated in academic
      settings.

PMID- 27022308
TI  - Kozhikode criteria for diagnosing systemic lupus erythematosus as a hematological
      disorder.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease in which cells and
      tissues undergo damage mediated by tissue-binding autoantibodies. At its onset,
      it may involve one organ alone or more than one organ simultaneously; over a
      time, additional manifestations due to the involvement of other organs may occur.
      Our observations have confirmed that hematological manifestations are the
      commonest initial presentation in SLE. The criteria used till 2012 was the
      American College of Rheumatology (ACR) criteria, which is only a classification
      criterion and not really for diagnosis; if we rely on ACR criteria, the diagnosis
      is often delayed. Time required for satisfying all four of the eleven criteria is
      variable and prolonged. Moreover, hematological manifestations are
      underrepresented in the ACR criteria. Based on the clinical observations made on
      patients evaluated in a tertiary center in North Kerala, an alternate diagnostic
      criterion named the Kozhikode criteria was proposed, especially for the diagnosis
      of SLE when it presents with hematological manifestations alone. The present
      study was an attempt to validate the same and to look for any association of diet
      and lifestyle with the disease. 

PMID- 27022307
TI  - Progress in elucidating the pathophysiological basis of nonrapid eye movement
      parasomnias: not yet informing therapeutic strategies.
AB  - Nonrapid eye movement (NREM) or arousal parasomnias are prevalent conditions in
      children and young adults, apparently provoked by any medical, physical, mental,
      or pharmacologic/toxic agent disturbing normal biorhythm and causing sleep
      fragmentation or abundant amount of slow wave sleep. The nadir and the ascending
      slope of the first sleep cycle of night sleep are the typical periods when NREM
      parasomnias, especially sleepwalking may occur on sleep-microstructural level;
      microarousals are the typical moments allowing NREM parasomnias. While sleep
      disturbing factors have a clear precipitating effect, a genetic predisposition
      appears necessary in most cases. A candidate gene for sleepwalking has been
      identified on chromosome 20q12-q13.12 in one sleepwalking family. NREM
      parasomnias have a genetic and clinical link with nocturnal-frontal lobe
      epilepsies; possibly through an abnormality of the acetylcholine-related sleep
      control system. The association of NREM parasomnias with the human leukocyte
      antigen system might be the sign of an autoimmune background to be further
      clarified. In the treatment of arousal parasomnias, the main tools are adequate
      sleep hygiene and the management of underlying conditions. Their pharmacotherapy
      has remained unresolved; the best options are clonazepam and some of the
      antidepressants, while a psychotherapy approach is also justified. 

PMID- 27022309
TI  - Perspectives of primary health care physicians on diagnosing and referring
      patients with apparent osteolytic lesions on plain X-ray films: a cross-sectional
      study.
AB  - BACKGROUND AND OBJECTIVES: The identification and diagnosis of musculoskeletal
      symptoms are major challenges for primary care physicians. A lack of clinical
      suspicion, limited exposure, and referral of patients to nonspecialized centers
      can delay the management of cases, which in turn can increase morbidity and
      mortality. SUBJECTS AND METHODS: Four different sets of X-ray films were shown to
      91 primary health care physicians. The first two were normal, whereas the third
      and fourth showed bone lesions. Participants were asked to indicate the presence
      of an abnormality, the diagnosis, and the approach to referral if required.
      RESULTS: There was a variation in the results for the first two sets of normal X
      ray films. Most participants (73.6%) were able to diagnose the first case
      correctly. However, 73.6% of participants were unable to diagnose the second case
      correctly. A high percentage of participants (90.1%) were able to detect
      abnormalities in Cases 3 and 4, with nearly all participants indicating that they
      would refer patients to centers other than bone oncology centers in the western
      region of Saudi Arabia if they suspected bone tumors. Only 25.8% of participants
      were aware of these bone oncology centers. CONCLUSION: Physicians in many primary
      health care centers need practice in reading normal X-ray films to avoid
      unnecessary referral of patients to specialized medical centers. We recommend the
      development of a new system for referring patients suspected to have bone tumors
      to avoid a delay in the management of cases and to decrease morbidity and
      mortality.

PMID- 27022310
TI  - In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (nbl) is one of the most common solid cancers in
      children. Prognosis in advanced nbl is still poor despite aggressive
      multimodality therapy. Furthermore, survivors experience severe long-term multi
      organ sequelae. Hence, the identification of new therapeutic strategies is of
      utmost importance. Cannabinoids and their derivatives have been used for years in
      folk medicine and later in the field of palliative care. Recently, they were
      found to show pharmacologic activity in cancer, including cytostatic, apoptotic,
      and antiangiogenic effects. METHODS: We investigated, in vitro and in vivo, the
      anti-nbl effect of the most active compounds in Cannabis, Delta(9)
      tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally
      determine the effects of those compounds on viability, invasiveness, cell cycle
      distribution, and programmed cell death in human nbl SK-N-SH cells. RESULTS: Both
      compounds have antitumourigenic activity in vitro and impeded the growth of
      tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more
      active. Treatment with cbd reduced the viability and invasiveness of treated
      tumour cells in vitro and induced apoptosis (as demonstrated by morphology
      changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited
      an increase in activated caspase 3 in treated cells and tumour xenografts.
      CONCLUSIONS: Our results demonstrate the antitumourigenic action of cbd on nbl
      cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of
      side effects, our results support its exploitation as an effective anticancer
      drug in the management of nbl.

PMID- 27022312
TI  - Use of cannabinoids in cancer care: palliative care.

PMID- 27022313
TI  - Cannabis and cancer: toward a new understanding.

PMID- 27022311
TI  - Anticancer mechanisms of cannabinoids.
AB  - In addition to the well-known palliative effects of cannabinoids on some cancer
      associated symptoms, a large body of evidence shows that these molecules can
      decrease tumour growth in animal models of cancer. They do so by modulating key
      cell signalling pathways involved in the control of cancer cell proliferation and
      survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis
      in various tumour types in laboratory animals. In this review, we discuss the
      current understanding of cannabinoids as antitumour agents, focusing on recent
      discoveries about their molecular mechanisms of action, including resistance
      mechanisms and opportunities for their use in combination therapy. Those
      observations have already contributed to the foundation for the development of
      the first clinical studies that will analyze the safety and potential clinical
      benefit of cannabinoids as anticancer agents. 

PMID- 27022314
TI  - Why I chose to use cannabis.

PMID- 27022315
TI  - Integrating cannabis into clinical cancer care.
AB  - Cannabis species have been used as medicine for thousands of years; only since
      the 1940s has the plant not been widely available for medical use. However, an
      increasing number of jurisdictions are making it possible for patients to obtain
      the botanical for medicinal use. For the cancer patient, cannabis has a number of
      potential benefits, especially in the management of symptoms. Cannabis is useful
      in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia,
      and depression. Cannabis might be less potent than other available antiemetics,
      but for some patients, it is the only agent that works, and it is the only
      antiemetic that also increases appetite. Inhaled cannabis is more effective than
      placebo in ameliorating peripheral neuropathy in a number of conditions, and it
      could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic
      interaction study of vaporized cannabis in patients with chronic pain on stable
      doses of sustained-release opioids demonstrated no clinically significant change
      in plasma opiates, while suggesting the possibility of synergistic analgesia.
      Aside from symptom management, an increasing body of in vitro and animal-model
      studies supports a possible direct anticancer effect of cannabinoids by way of a
      number of different mechanisms involving apoptosis, angiogenesis, and inhibition
      of metastasis. Despite an absence of clinical trials, abundant anecdotal reports
      that describe patients having remarkable responses to cannabis as an anticancer
      agent, especially when taken as a high-potency orally ingested concentrate, are
      circulating. Human studies should be conducted to address critical questions
      related to the foregoing effects. 

PMID- 27022316
TI  - Reversible Oxygenation of alpha-Amino Acid-Cobalt(II) Complexes.
AB  - We systematically investigated the reversibility, time lapse, and oxygenation
      deoxygenation properties of 15 natural alpha-amino acid-Co(II) complexes through
      UV-vis spectrophotometer, polarographic oxygen electrode, and DFT calculations,
      respectively, to explore the relationship between the coordinating structure and
      reversible oxygenation of alpha-amino acid-Co(II) complexes. Results revealed
      that the alpha-amino acid structure plays a key role in the reversible
      oxygenation properties of these complexes. The specific configuration of the
      alpha-amino acid group affects the eg (1) electron of Co(II) transfer to the pi
      (*) orbit of O2; this phenomenon also favors the reversible formation and
      dissociation of Co-O2 bond when O2 coordinates with Co(II) complexes. Therefore,
      the co-coordination of amino and carboxyl groups is a determinant of Co complexes
      to absorb O2 reversibly. The group adjacent to the alpha-amino acid unit
      evidently influences the dioxygen affinity and antioxidation ability of the
      complexes. The presence of amino (or imino) and hydroxy groups adjacent to the
      alpha-amino acid group increases the oxygenation-deoxygenation rate and the
      number of reversible cycles. Our findings demonstrate a new mechanism to develop
      reversible oxygenation complexes and to reveal the oxygenation of oxygen
      carriers. 

PMID- 27022317
TI  - ABO-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option
      for a variety of malignant and non-malignant hematological and congenital
      diseases. Due to the fact that the human leukocyte antigen system is inherited
      independently of the blood group system, approximately 40-50% of all HSCTs are
      performed across the ABO blood group barrier. The expected immune-hematological
      consequences after transplantation of an ABO-mismatched stem cell graft are
      immediate and delayed hemolytic complications due to presence of
      isohemagglutinins or passenger lymphocyte syndrome. The risks of these
      complications can partially be prevented by graft manipulation and appropriate
      transfusion support. Dependent on the kind of ABO mismatch, different effects on
      engraftment have been observed, e.g. delayed red blood cell recovery and pure red
      cell aplasia. Data on incidence of acute graft-versus-host disease (GVHD), non
      relapse mortality, relapse, and overall survival are inconsistent as most studies
      include limited patient numbers, various graft sources, and different
      conditioning and GVHD prophylaxis regimens. This makes it difficult to detect a
      consistent effect of ABO-mismatched transplantation in the literature. However,
      knowledge of expectable complications and close monitoring of patients helps to
      detect problems early and to treat patients efficiently, thus reducing the number
      of fatal or life-threatening events caused by ABO-mismatched HSCT. 

PMID- 27022318
TI  - Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation.
AB  - ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell
      transplants. Major, minor and bidirectional ABO-incompatible transplants each
      have unique complications that can occur, including hemolysis at the time of
      progenitor cell infusion, hemolysis during donor engraftment, passenger
      lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell
      aplasia. Appropriate transfusion support during the different phases of the
      allogeneic progenitor cell transplant process is an important part of ABO
      incompatible transplantation. 

PMID- 27022319
TI  - Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without
      Altering the Lipid Composition of the Vesicles.
AB  - BACKGROUND: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate
      (DEHP) is commonly used for blood collection and storage. DEHP has protective
      effects on RBC membranes, but is also a toxin. METHODS: A paired study was
      conducted to investigate the influence of DEHP and two alternative plasticizers,
      1,2-cyclohexane-dicarboxylic acid diisononyl ester (DINCH) and n-butyryl-tri-n
      hexyl citrate (BTHC), on the preservation of RBCs stored for 42 days in PVC
      pediatric bags. The RBC membrane was evaluated for supernatant hemoglobin (Hb),
      release of extracellular microvesicles (EVs), osmotic fragility, deformability,
      and lipid composition. RESULTS: In BTHC-plasticized bags, the supernatant Hb
      increase during storage was 2 times greater than in DINCH- and DEHP-plasticized
      bags. By day 21, EV concentrations had doubled from day-5 levels in DINCH- and
      DEHP-, and trebled in BTHC-plasticized bags. RBC mean cell volumes were greater
      in BTHC- than in DINCH- or DEHP-plasticized bags (p < 0.001). Osmotic fragility
      differed significantly among plasticizers (p < 0.01). After day 21, RBC
      deformability decreased in all, but to a greater extent in the bags with BTHC.
      Phospholipid composition of RBCs and EVs was not different among plasticizers.
      CONCLUSION: Membrane stabilization capacity differed among the plasticizers. RBC
      in BTHC bags stored more poorly, while DEHP and DINCH bags offered better
      protection against vesiculation, osmotic stress, and Hb loss.

PMID- 27022320
TI  - Implementation of NAT Screening for West Nile Virus and Experience with Seasonal
      Testing in Germany.
AB  - BACKGROUND: West Nile virus (WNV) can be transmitted by transfusion through
      infected blood components. In Germany, a 28-day deferral for blood donors of
      therapeutic blood components who had spent at least 2 days in WNV-endemic areas
      from June 1 to November 30, 2014 was enforced. Otherwise, screening of blood
      donors for WNV RNA or the application of pathogen reduction techniques are
      appropriate alternatives. METHODS: In the present study, we evaluated NAT
      screening for the detection of WNV in blood components. A total of 58 minipools
      consisting of 357 individual blood donors were screened for the presence of WNV
      RNA employing an automated high-volume extraction method using the RealStar WNV
      RT-PCR Kit. Additionally, different WNV reference reagents were quantified to
      prove the status quo of standardization. Four different WNV real-time NAT kits
      were compared using samples of an external quality assessment panel. RESULTS: The
      95% lower detection limit of the WNV MP-NAT was determined to 30.2 copies/ml (95%
      CI 24.2-45.4 copies/ml). No WNV RNA-positive minipool was detected.
      Quantification of WNV reference reagents revealed shortcomings in
      standardization. Comparison of several WNV NAT assays showed considerable
      differences in assay sensitivities and particularly a missing detection of WNV
      lineage 2. Implementation of seasonal WNV MP-NAT screening was demonstrated.
      CONCLUSION: Actually, WNV infections in Germany are rare events introduced by
      returning travelers, but surveillance of these emerging infections is important
      for safety in blood supply. The validation study pointed out the need for
      standardization of WNV NAT because of current lack of an international standard
      for WNV RNA.

PMID- 27022321
TI  - Comparison of Two Test Strategies for Clarification of Reactive Results for Anti
      HBc in Blood Donors.
AB  - OBJECTIVE: Testing for antibodies against hepatitis B core antigen (anti-HBc) was
      introduced to detect blood donors suffering from occult hepatitis B infection.
      Confirmation of specification of reactive results in the anti-HBc screening assay
      is still a challenge for blood donation services. METHODS: Two different test
      strategies for confirmation of specification of reactive anti-HBc tests, one
      performed in our institute and one suggested by the German authority (Paul
      Ehrlich-Institut (PEI)), were compared. The first strategy is based on one
      supplemental anti-HBc test, the other requires two supplemental anti-HBc tests.
      RESULTS: 389 samples from 242 donors were considered. Both test strategies
      yielded concordant results in 117 reactive samples termed 'true-positive' or
      'specificity confirmed', in 156 reactive samples termed 'false-positive' or
      'specificity not confirmed', and in 99 negative samples. In 17 samples obtained
      from 11 donors, both test strategies gave discrepant results ('false-positive'
      but 'specificity confirmed'). In 10 of 11 donors, a real HBV infection was very
      unlikely, one remained unclear. 30 donors considered 'false-positive' became
      negative in all anti-HBc tests after follow-up testing and thus eligible for
      donor re-entry. CONCLUSIONS: The test strategy suggested by the PEI yielded no
      additional information but induced an overestimation of HBV infections and
      unnecessary look-back procedures. Many anti-HBc-reactive donors can be regained
      after follow-up testing.

PMID- 27022322
TI  - Changes of Thyroid Hormones and Their Binding Proteins during Plasma Exchange for
      Polyneuropathy in a Patient with Substituted Hypothyroidism due to Hashimoto's
      Thyroiditis.
AB  - BACKGROUND: Pharmacodynamic studies and data concerning adaptation of thyroid
      substitution in patients with substituted hypothyroidism during plasma exchange
      (PE) is not available. CASE REPORT: We measured TSH, fT3 and fT4, total T4,
      thyroxin binding globulin (TBG), and albumin before and after 5 PE procedures in
      a 37-year-old women who underwent PE for a therapy-resistant polyneuropathy.
      Thyroxin was increased empirically by 8% resulting in a dose of 1.95 ug/kg per
      day. RESULTS: Despite larger reductions of total T4 and TBG over a series of 5
      PEs (40-50% from baseline), only small reductions of 8% in fT3 and fT4
      concentrations were documented with a concomittant increase in TSH level. Changes
      of fT4, fT3, and TSH remained within normal range. CONCLUSIONS: i) Despite a
      significant decrease in total thyroid hormone pool following PE, fT4, fT3, and
      TSH concentrations changed only slightly. ii) Based on this observation, a
      general increase in thyroid replacement therapy before PE cannot be recommended,
      but considered in case of a high normal TSH level.

PMID- 27022323
TI  - Comments on the Judgement of the Court of Justice of the European Union of April
      29, 2015: Is the Permanent Exclusion of MSM from Giving Blood Compatible with the
      Directive 2004/33/EC? What Are the Consequences for Blood Donations in Germany?

PMID- 27022324
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000440821.]. 

PMID- 27022325
TI  - From Telomere Crisis via Dicentric Chromosomes to Kataegis and Chromothripsis.

PMID- 27022326
TI  - Involvement of Fibroblast Growth Factors and Their Receptors in Epididymo
      Testicular Descent and Maldescent.
AB  - Maldescent of the epididymo-testicular unit can occur as an isolated event or as
      a component of various syndromes. When part of a syndrome, crypto-epididymis is
      usually accompanied by other genital and/or extragenital features. Epididymis
      development is primarily regulated by androgens, and successful epididymo
      testicular unit development and descent requires an intact hypothalamic-pituitary
      gonadal axis. The developing gonadotropin-releasing hormone system is essential
      for epididymo-testicular descent and is highly sensitive to reduced fibroblast
      growth factor (FGF) signaling. Our understanding of the impact of FGFR1 in the
      process of epididymo-testicular descent has recently improved. At later stages of
      embryonic development, the undifferentiated epididymal mesenchyme is a specific
      domain for FGFR1 expression. The majority of individuals with syndromic crypto
      epididymis, as well as individuals with isolated maldescent of the epididymo
      testicular unit, exhibit some disturbance of FGF, FGFR1 and/or genes involved in
      hypothalamic-pituitary-gonadal axis regulation. However, the mechanisms
      underlying FGF dysregulation may differ between various syndromes. 

PMID- 27022327
TI  - Differing Microdeletion Sizes and Breakpoints in Chromosome 7q11.23 in Williams
      Beuren Syndrome Detected by Chromosomal Microarray Analysis.
AB  - Williams-Beuren syndrome (WBS) manifests as supravalvular aortic stenosis,
      intellectual disability, developmental delay and characteristic facial features.
      The common WBS deletion region ranges from 1.55 to 1.84 Mb and primarily contains
      the ELN gene. We analyzed 10 patients diagnosed with 7q11.23 microdeletion
      syndrome by chromosomal microarray analysis. The clinical features of these
      patients varied from classic WBS to normal phenotype. All 10 patients exhibited
      different sizes and breakpoints of chromosome microdeletions ranging from 44 kb
      to 9.88 Mb. The hemizygosity of the ELN gene was detected in 7 patients, while a
      normal ELN gene was present in 3 other patients with small deletions. We observed
      that the phenotypic features of WBS varied in fetuses, children and adults,
      influenced by the genes, deletion size and breakpoint. Our findings provide more
      information on the genotype-phenotype correlations of WBS. However, further
      research is needed to explore the size and breakpoint effect and functions of the
      genes on chromosome 7q11.23. 

PMID- 27022328
TI  - Genomic Alterations Are Enhanced in Placentas from Pregnancies with Fetal Growth
      Restriction and Preeclampsia: Preliminary Results.
AB  - Fetal growth restriction (FGR) secondary to placental insufficiency and
      preeclampsia (PE) are associated with substantially increased childhood and adult
      morbidity and mortality. The long-term outcomes are related to placental
      aberrations and intrauterine programming. Advances in microarray technology allow
      high-resolution, genome-wide evaluation for DNA copy number variations -
      deletions and duplications. The aim of our study was to demonstrate the
      usefulness of microarray testing in FGR placentas. Using Affymetrix GeneChip for
      chromosomal microarray (CMA), we analyzed 10 placentas from pregnancies with FGR
      attributed to placental insufficiency; 5 with FGR below the 5th percentile and 5
      from the 5th to <10th percentiles. All fetuses had normal anomaly scans and
      karyotypes. We also analyzed 5 third-trimester placentas from pregnancies
      complicated by PE with severe features and 5 from PE without severe features, all
      with appropriately grown fetuses. The results were compared to 10 placentas from
      uncomplicated pregnancies with healthy neonates. CMA analysis identified more
      genomic alterations in FGR (p < 0.05) and in PE (p < 0.05) placentas than in
      healthy controls. There was a correlation to the severity of FGR and PE. The
      genomic alterations were below the resolution of normal karyotyping. The altered
      genes are related to adult human height, stress reactions and to cellular
      migration, differentiation and adhesion. Though very preliminary, our data
      support evaluating FGR and PE placentas using CMA. Larger data sets are needed
      for further evaluation of the findings and their clinical implications. 

PMID- 27022329
TI  - Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation
      outside the Neonatal Domain.
AB  - We report a child and her mother affected by Marfan syndrome. The child presented
      with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory
      heart failure, finally leading to death within the first 4 months of life. Her
      mother had a common clinical presentation. Genetic analysis revealed an inherited
      FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date,
      leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids
      (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument
      for mosaicism. Association in the same family of severe neonatal and classical
      Marfan syndrome illustrates the intrafamilial phenotype variability. 

PMID- 27022330
TI  - Split Hand/Foot Malformation Associated with 7q21.3 Microdeletion: A Case Report.
AB  - Split hand/foot malformation (SHFM) or ectrodactyly is a rare genetic condition
      affecting limb development. SHFM shows clinical and genetic heterogeneity. It can
      present as an isolated form or in combination with additional anomalies affecting
      the long bones (nonsyndromic form) or other organ systems including the
      craniofacial, genitourinary and ectodermal structures (syndromic ectrodactyly).
      This study reports a girl with SHFM who also exhibited developmental delay, mild
      dysmorphic facial features and sensorineural hearing loss. High-resolution
      banding analysis indicated an interstitial deletion within the 7q21 band. FISH
      using locus-specific BAC probes confirmed the microdeletion of 7q21.3.
      Chromosomal microarray analysis also revealed a microdeletion of 1.856 Mb in
      7q21.3. However, a larger 8.44-Mb deletion involving bands 7q21.11q21.2 was
      observed, and the breakpoints were refined. The phenotype and the candidate genes
      underlying the pathogenesis of this disorder are discussed. 

PMID- 27022331
TI  - Partial 1q Duplications and Associated Phenotype.
AB  - Duplications of the long arm of chromosome 1 are rare. Distal duplications are
      the most common and have been reported as either pure trisomy or unbalanced
      translocations. The paucity of cases with pure distal 1q duplications has made it
      difficult to delineate a partial distal trisomy 1q syndrome. Here, we report 2
      patients with overlapping 1q duplications detected by G-banding. Array CGH and
      FISH were performed to characterize the duplicated segments, exclude the
      involvement of other chromosomes and determine the orientation of the
      duplication. Patient 1 presents with a mild phenotype and carries a 22.5-Mb
      1q41q43 duplication. Patient 2 presents with a pure 1q42.13qter inverted
      duplication of 21.5 Mb, one of the smallest distal 1q duplications ever described
      and one of the few cases characterized by array CGH, thus contributing to a
      better characterization of distal 1q duplication syndrome. 

PMID- 27022332
TI  - Left Ventricular Mass and Intrarenal Arterial Stiffness as Early Diagnostic
      Markers in Cardiorenal Syndrome Type 5 due to Systemic Sclerosis.
AB  - BACKGROUND: Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions
      characterized by a simultaneous involvement of the heart and kidney in the course
      of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the
      etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc
      patients, left ventricular mass (LVM) can be used as a marker of nutritional
      status and fibrosis, while altered intrarenal hemodynamic parameters are
      suggestive of early kidney involvement. METHODS: Forty-two consecutive patients
      with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to
      assess whether cardiac muscle mass can be related to arterial stiffness. Thirty
      subjects matched for age and sex were also enrolled as healthy controls (HC). All
      patients performed echocardiography and renal ultrasound. RESULTS: Doppler
      indices of intrarenal stiffness and echocardiographic indices of LVM were
      significantly increased in SSc patients compared to HC. A positive correlation
      exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36),
      resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r =
      0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly
      higher in SSc patients with digital ulcers than in SSc patients without a digital
      ulcer history. CONCLUSIONS: SSc is characterized by the presence of microvascular
      and multiorgan injury. An early cardiac and renal impairment is very common. LVM
      and intrarenal arterial stiffness can be considered as early markers of CRS
      onset. The clinical use of these markers permits a prompt identification of organ
      damage. An early diagnosis allows the appropriate setting of pharmacological
      management, by slowing disease progression. (c) 2016 S. Karger AG, Basel.

PMID- 27022333
TI  - Prevention and intervention strategies to check increasing violence against
      Healthcare Facilities and Healthcare Professionals.

PMID- 27022334
TI  - Fertilization rate and its determinants in intracytoplasmic sperm injection.
AB  - OBJECTIVE: To identify predictors of fertilization rate in patients of
      unexplained infertility after intracytoplasmic sperm injection (ICSI). METHODS:
      Retrospective analysis of females (282) enrolled in quasi experimental design for
      ICSI at "Islamabad Clinic Serving Infertile Couples" was carried out from July
      2013 till June 2014. Females with unexplained infertility were included, whereas
      well defined male and female causes of infertility were excluded. Fertilization
      rate (FR) was calculated as percentage transformation of micro injected oocytes
      into two pronuclei. Categorical variable of FR defined on the basis of 50% FR
      grouped females; Group I with FR <=50% and Group II with FR >50%. The groups were
      compared in terms of demographic variables, base line hormones and oocyte
      parameters. Univariate logistic regression was executed to obtain odds ratio with
      95% confidence interval to quantify the association of predictors like age,
      duration of infertility, oocytes parameters, hormones; Estradiol, progesterone,
      follicle stimulating hormone (FSH), luteinizing hormone, prolactin and cytokines
      interleukin-Ibeta (IL-Ibeta) with the FR. RESULTS: In our study out of 282
      females, 19 (6.73%) were in group I and 263 (93.26%) comprised of Group II.
      Females with high FR(group II) had low Progesterone and FSH (p=0.04, p=0.02)
      respectively. Mature oocytes (OR: 0.35; 95% CI 1 - 2.56) and IL-Ibeta in
      follicular phase (OR: 1.04; 95% CI: 0.000- 1.20) were significant positive
      predictors of FR while peak progesterone and FSH had significant negative effect
      on it. CONCLUSION: Fertilization of oocytes in females of unexplained infertility
      depended on maturity of oocytes and optimal amounts of ILI- beta released by
      developing follicles in the follicular phase of stimulation cycles of ICSI.

PMID- 27022335
TI  - Imaging changes after breast reconstruction with fat grafting - Retrospective
      study of 90 breast cancer.
AB  - OBJECTIVE: To evaluate the breast imaging changes after fat grafting and its
      impact on cancer follow up. METHODS: This is a retrospective observational study
      conducted on patients who underwent fat grafting for breast reconstruction. We
      reviewed mammographic and ultrasound images of patients. Fisher's exact test was
      used to analyze results. The level of significance was set at P < 0.05. RESULTS:
      A total of ninety patients with breast cancer had fat grafting. Fifty eight
      patients for defects following post mastectomy reconstruction and 32 for wide
      local excision defects. The mean follow up was 37.4 months. Benign lumps were
      identified in 23/90 cases (25 percent). Mammograms were reported as BI-RADS I in
      21/32 cases (72 percent) and BI-RADS II in 8/32 cases (28 percent). BI-RADs III
      score was reported in two patients on further follow up imaging, both were re
      classified as BI-RADS II after biopsy. A total of eight patients (8.9 percent)
      required biopsy. No local recurrences or new cancers were observed in any
      patients. CONCLUSION: Our study suggests radiological changes after fat grafting
      are almost always benign with no adverse outcome on cancer follow up.

PMID- 27022337
TI  - The effects of Ramadan fasting on the number of renal colic visits to the
      emergency department.
AB  - OBJECTIVE: The effects of fluid and diet restriction strictly during the long
      hours in Ramadan on the number of colic visits and biochemical factors of stone
      formation are controversial in the literature. The aim of this study was to
      assess the effects of Ramadan fasting on the number of renal colic visits and
      laboratory results of patients with renal colic. METHODS: This was a prospective
      observational study, which was conducted with patients who were admitted to our
      emergency department with renal colic. The study period was divided into two
      parts: Before Ramadan and Ramadan. All laboratory results of patients and daily
      air temperature values were recorded. p<0.05 was considered statistically
      significant for all tests. RESULTS: Total 176 patients (n:89 in before Ramadan,
      n:87 in Ramadan) with renal colic were enrolled into the study. During Ramadan,
      49 (73.1%) of 67 patients were admitted in the first half of the month and 20
      patients (26.9%) were admitted in the second half of the month. Only urine
      density and white blood cell values in Ramadan and non-Ramadan period were
      significantly different (p=0.004 and p=0.001). Hemoglobin, general crystal, and
      triple phosphate crystal values in the first and the second half of Ramadan were
      significantly different (p=0.04, p=0.03, and p=0.03). CONCLUSION: This study has
      shown that fasting in Ramadan does not change the number of renal colic visits.
      In addition, although fasting causes some changes in urinary metabolites, there
      is not enough evidence that these changes increase urinary calculus formation.

PMID- 27022336
TI  - Clinical outcomes of endovascular aneurysm repair of abdominal aortic aneurysm
      complicated with hypertension: A 5-year experience.
AB  - OBJECTIVE: To evaluate the therapeutic effects of endovascular aneurysm repair
      (EVAR) on abdominal aortic aneurysm (AAA) complicated with hypertension. METHODS:
      Fifty-two patients with AAA complicated with hypertension treated in our hospital
      were retrospectively analyzed. They were divided into an observation group (34
      cases) and a control group (18 cases). The control group was treated by incision
      of AAA and artificial blood vessel replacement, and the observation group was
      treated by EVAR. RESULTS: All surgeries were performed successfully. However,
      compared with the control group, the observation group had significantly less
      surgical time, intraoperative blood loss and blood transfusion, as well as
      significantly higher total hospitalization expense (P<0.05). During the one-month
      follow-up, the observation group was significantly less prone to pulmonary
      infection, surgical site infection, lower-extremity deep venous thrombosis and
      lower extremity weakness than the control group (P<0.05). The observation group
      enjoyed significantly better quality of life than the control group did one and
      three months after surgery (P<0.05). CONCLUSION: Given sufficient funding, EVAR
      should be preferentially selected in the treatment of AAA complicated with
      hypertension due to minimal invasion, safety, stable postoperative vital signs
      and improved quality of life.

PMID- 27022338
TI  - Comparison of Gabapentin and Ketotifen in Treatment of Uremic Pruritus in
      Hemodialysis Patients.
AB  - OBJECTIVES: Uremic pruritus is a common problem in hemodialysis patients. Several
      treatments have been used for decreasing itching in these patients. Gabapentin
      and ketotifen are two drugs used for treating uremic patients. The aim of this
      study was to compare gabapentin and ketotifen in treatment of uremic pruritus in
      hemodialysis patients. METHODS: In this double-blind randomized clinical trial,
      52 hemodialysis patients with uremic pruritus referred to 5azarTeaching Hospital
      in Gorgan in 2013 were studied. Patients were randomly assigned to two groups of
      26 subjects (groups G and K). In group G, patients treated with gabapentin
      capsules 100 mg daily for 2 weeks, and in Group K, patients treated with
      ketotifen 1 mg twice daily for 2 weeks. Before and at the end of study, pruritus
      severity was determined based on Shiratori's severity scores. Collected data were
      analyzed by SPSS-21 statistical software. RESULTS: There was no significant
      different between two groups in the age and sex. After two weeks of treatment,
      severity of pruritus was significantly reduced in both groups (88.4% in group G
      vs. 76.9% in group K). Gabapentin compared with ketotifen had a better effect on
      improving itching in the age group of 30-60 years and in males. 5 patients
      (19.2%) in both groups suffered from drowsiness and dizziness, but no serious
      side effects were observed. CONCLUSIONS: The results showed that gabapentin and
      ketotifen significantly improved pruritus in hemodialysis patients, and no
      significant difference was observed between two groups.

PMID- 27022339
TI  - Risk profiles of referred chronic kidney disease patients in a tertiary
      nephrology centre.
AB  - OBJECTIVE: To determine the risk profile of chronic kidney disease (CKD)
      patients. METHODS: This is an observational cross sectional study involving 130
      patients for which data was collected prospectively.. Sixty five subjects with an
      estimated glomerular filtration rate (eGFR) below 120 ml/min/1.73 m(2) were
      recruited via random sampling technique from nephrology clinic in a tertiary
      nephrology referral center. Medical history, demographic data, urinary and serum
      biochemistry tests were obtained. RESULTS: Most of the CKD patients who were
      referred to the nephrology clinic were asymptomatic. The most common laboratory
      abnormalities noted among CKD patients were proteinuria, anaemia and
      hyperkalaemia. Advancing age, pre-existing morbidities such as diabetes mellitus,
      hypertension and overweight are characteristics that are strongly associated with
      the referred CKD patients. CONCLUSIONS: Most of the referred CKD patients are in
      advanced age with diabetes, hypertension and overweight. Majority of the CKD
      remained asymptomatic despite in the advance stage of CKD. This strongly calls
      for cost effective screening for population at risk.

PMID- 27022340
TI  - Comparison between effectiveness of Mechanical and Manual Traction combined with
      mobilization and exercise therapy in Patients with Cervical Radiculopathy.
AB  - BACKGROUND AND OBJECTIVE: Cervical radiculopathy is a common neuro-musculo
      skeletal disorder causing pain and disability. Traction is part of the evidence
      based manual physical therapy management due to its mechanical nature, type of
      traction and parameters related to its applicability and are still to be explored
      more through research. Our objective was to determine the Effects of Mechanical
      versus Manual Traction in Manual Physical Therapy combined with segmental
      mobilization and exercise therapy in the physical therapy management of Patients
      with Cervical Radiculopathy. METHODS: This randomized control trial was conducted
      at department of physical therapy and rehabilitation, Rathore Hospital
      Faisalabad, from February to July 2015. Inclusion criteria were both male and
      female patients with evident symptoms of cervical spine radiculopathy and age
      ranged between 20-70 years. The exclusion criteria were Patients with history of
      trauma, neck pain without radiculopathy, aged less than 20 and more than 70. A
      total of 72 patients with cervical radiculopathy were screened out as per the
      inclusion criteria, 42 patients were randomly selected and placed into two groups
      by toss and trial method, and only 36 patients completed the study, while 6
      dropped out. The mechanical traction was applied in group A and manual traction
      in group B along with common intervention of segmental mobilization and exercise
      therapy in both groups for 6 weeks. The patient's outcomes were assessed by self
      reported NPRS and NDI at the baseline and after completion of 06 weeks exercise
      program at 3 days per week. The data was analyzed through SPSS version-21, and
      paired T test was applied at 95% level significance to determine the statistical
      deference between two groups. RESULTS: Clinically the group of patients treated
      with mechanical traction managed pain (mean pre 6.26, mean post 1.43), and
      disability (mean pre 24.43 and mean post 7.26) more effectively as compared with
      the group of patients treated with manual traction (Pain mean pre 6.80, mean post
      3.85 and disability mean pre 21.92 and post 12.19). Statistically the results of
      both mechanical and manual traction techniques are equally significant in group A
      and B for pain and disability (p-value less than 0.05). CONCLUSION: If patients
      of cervical radiculopathy treated with mechanical traction, segmental
      mobilization, and exercise therapy will manage pain and disability more
      effectively than treated with manual traction, segmental mobilization, and
      exercise therapy.

PMID- 27022341
TI  - Double-lumen tube intubation using video laryngoscopy causes a milder
      cardiovascular response compared to classic direct laryngoscopy.
AB  - OBJECTIVE: To determine whether there is a clinically relevant difference between
      the circulatory responses to double-lumen tube intubation (DLTI) with the
      GlideScope video laryngoscope versus the Macintosh direct laryngoscope. METHODS:
      Eighty adult patients requiring double-lumen tubes for thoracic surgery were
      randomly and equally allocated to either a Macintosh direct laryngoscope group
      (DL group, n = 40) or a Glide Scope video laryngoscope group (GS group, n = 40).
      DLTI was performed after airway evaluations and induction of anesthesia. Systolic
      blood pressure (SBP) and heart rate (HR) were recorded before induction (baseline
      values), immediately before intubation (post-induction values), at intubation and
      after intubation. Rate-pressure-product (RPP), and the areas under SBP- and HR
      time curves were calculated. All data obtained by the two devices were compared.
      RESULTS: After laryngoscope insertion, SBP of DL and GS groups changed
      significantly differently (13.1% vs. 4.6%, P< 0.001), while HR changed similarly
      (17.2% vs. 14.6%, P = 0.074). One minute after intubation, both SBP and HR
      significantly increased in both groups (SBP: 11.6% vs. 11.9%; HR: 18.4% vs.
      10.8%), but there were no significant differences between the two groups. RPP
      significantly increased in both groups after laryngoscope insertion (32.6%,
      P=0.001; 18.2%, P=0.002), and there was a significant difference between the two
      groups (P =0.001). Throughout intubation, the areas under SBP-time curves had a
      significant difference between the two groups (P = 0.042), while those under HR
      time curves did not differ significantly (P=0.06). CONCLUSION: The intubation
      response was most significant upon laryngoscope insertion during the whole
      intubation process. The GlideScope video laryngoscope induced milder circulatory
      fluctuations than the Macintosh direct laryngoscope did, suggesting that DLTI
      using video laryngoscopy can help reduce the cardiovascular response to
      intubation.

PMID- 27022342
TI  - Comparison of blood and urine nephrin levels in preeclampsia and intrauterine
      growth retardation.
AB  - OBJECTIVE: To evaluate the relation between nephrin levels and preeclampsia
      severity by comparing serum and urine levels of nephrin in the severe and mild
      groups according to severity of associated intrauterine growth retardation (IUGR)
      development. METHODS: A total of 150 patients who attended our ante-natal clinic
      (ANC) were included in this study. We had 5 groups; Group 1:30 patients with mild
      preeclampsia (MP) and normal fetal development (NFD), Group 2:30 patients with
      severe preeclampsia (SP) and NFD, Group 3: 30 patients with MP and IUGR, Group 4:
      30 patients with SP and IUGR and Group 5: 30 volunteers who were normotensive and
      non-preeclamptic. We obtained both blood and urine samples for measuring nephrin
      levels. RESULTS: Both serum and urine nephrin levels were significantly higher
      for the fourth group compared with all other groups (p<0.001). The levels of SP
      group with NFD were measured considerably higher than MP group out of IUGR and
      control group (p<0.001). Urine and serum nephrin levels with gestational age of
      delivery showed a negative correlation (r=-0.621, p<0.001) and also urine and
      serum nephrin levels with birth weight showed a negative correlation too (r=
      0.655 p<0.001). CONCLUSION: Both serum and urine nephrin levels correlated with
      the severity of preeclampsia and IUGR development.

PMID- 27022343
TI  - Cemented versus uncemented hemiarthroplasty in patients with displaced femoral
      neck fractures.
AB  - OBJECTIVE: This study compared functional outcomes and preoperative between
      cemented and uncemented bipolar hemiarthroplasty in patients older than 65 years
      with subcapital displaced femoral neck fracture. METHODS: Fifty one patients with
      displaced femoral neck fracture were enrolled in this study. Twenty nine patients
      underwent uncemented bipolar hemiarthroplasty and 22 underwent cemented bipolar
      hemiarthroplasty. Physical examination and radiographs were performed at the
      first and sixth months after operation and results were recorded. The patients'
      pain and function were measured with Visual analogue Scale and with Harris Hip
      Score (HHS), respectively and then compared with each other. RESULTS: The mean
      duration of follow up was 18.9 and 19.5 months in the cemented and uncemented
      groups, respectively. All patients were followed up for at least 6 months. Mean
      operation and bleeding times were longer in the cemented group compared to the
      uncemented group (P>0.05). The mean pain score was significantly less in the
      cemented group compared to the uncemented group (P=0.001). Hip functional outcome
      based on HHS was more in the cemented group (P= 0.001). The intraoperative and
      postoperative complication rate was higher in the uncemented group (P<0.05).
      CONCLUSION: Although higher rates of intraoperative bleeding and surgery time
      were seen with cemented bipolar hemiarthroplasty in older patients with femoral
      neck fracture compared to uncemented bipolar hemiarthroplasty, cemented bipolar
      hemiarthroplasty can cause less complications and improve patients' function in
      less time.

PMID- 27022344
TI  - Perceptions, Perceived Barriers, and Practices of Physicians' towards Evidence
      Based Medicine.
AB  - OBJECTIVE: To investigate physicians' perceptions and practices towards Evidence
      Based Medicine (EBM) and physicians perceived barriers in one institute of Saudi
      Arabia. METHODS: One hundred seventeen practicing physicians at King Abdulaziz
      University Hospital, Jeddah were included in the study. A validated questionnaire
      was used for collecting data. The questionnaire had four parts and included
      questions addressing perceptions and practices about EBM as well as associated
      variables and barriers to practicing it. RESULTS: The majority of the respondents
      had a positive attitude toward EBM. Only 23.9% of participants reported that they
      are incorporating EBM into their practice. Knowledge about EBM databases was not
      good. The most common "regularly" read journal was the New England Journal of
      Medicine (31.6%), followed by the British Medical Journal (12.0%). Some of the
      respondents had an understanding and were able to explain to others the technical
      terms use in EBM such as odds ratio (19.7%), relative risk (22.2%), absolute risk
      (23.9%) and others. The major perceived barriers to practicing EBM was the lack
      of free personal time (27.4%), availability and access to information (27.4%),
      difficulties in involving in whole practice (12.0%) and lack of investment by
      health authorities (12.8%). CONCLUSION: The attitude of the practicing doctors
      towards EBM was good, but knowledge and practice were not up to the mark.

PMID- 27022345
TI  - The endovenous laser treatment for patients with varicose veins.
AB  - OBJECTIVE: To evaluate the clinical effect of endovenous laser treatment (EVLT)
      for patients with varicose veins. METHODS: Our series included 117 patients who
      underwent EVLT combined with high ligation and stripping since the introduction
      of the technique in our institution. All EVLT procedures were performed with
      local skin cooling to prevent skin burns, as well as stripping after
      exsanguinations to prevent thrombotic phlebitis. RESULTS: A total of 146 limbs in
      117 patients were ablated by EVLT. Bilateral EVLT was performed in 29 patients,
      with the remaining 88 patients undergoing unilateral EVLT. The mean age of the
      patients was 57 years +/- 12 years (range: 21 years to 80 years), and 56 were
      male and 61 were female. Follow-up for all patients lasted three to six months.
      The most common complication was induration and swelling, which was observed in
      64 patients, followed by paraesthesia in 27, and skin burns in 12. CONCLUSION:
      The treatment with endovenous laser treatment for patients with varicose veins is
      safe and effective.

PMID- 27022346
TI  - The relationship between HbA1c & atrial fibrillation after off-pump coronary
      artery bypass surgery in diabetic patients.
AB  - OBJECTIVE: Diabetes mellitus is recognized as a risk factor for mortality and
      morbidity after coronary bypass grafting. We aimed to determine the association
      between preoperative hemoglobin HbA1c and AF after isolated off-pump coronary
      bypass grafting (OPCAB). METHODS: The seventy-two diabetic patients undergoing
      isolated off-pump coronary bypass grafting were retrospectively analyzed for AF.
      They were divided into; Low (4.8-5.4%), Medium (5.5-8%) and High (8.1-11.5%)
      groups. The three groups were compared with respect to demographic,
      echocardiographic, intraoperative and postoperative clinical characteristics
      correlation. RESULTS: Three patients died during postoperative period. AF
      occurred in 12 patients (16.6%) after surgery. The incidence of postoperative AF
      was 15.3% in the lower, 4.4% middle and 57.1% upper group. There was
      statistically significant correlation between preoperative HbA1C and preoperative
      stroke, preoperative MI history, Left atrial (LA) size, preoperative
      levosimendan, preoperative clopidogrel, postoperative AF, postoperative dopamine
      and dobutamine use, IABP, duration of extubation time, 24-hour chest tube
      drainage, duration of ICU and hospital mortality. Univariate logistic regression
      analysis showed significant correlation between postoperative AF and variables
      like preoperative HbA1c levels, LVEF<30%, history of preoperative MI,
      preoperative use of levosimendan, preoperative use of clopidogrel, postoperative
      dopamine, dobutamine adrenaline use, left atrium size, 24-hour chest tube
      drainage and length of stay in the intensive care unit. CONCLUSION: Preoperative
      HbA1c levels could predict the occurrence of postoperative AF in diabetic
      patients and may entail to administer protective strategies.

PMID- 27022347
TI  - Comparison of negative pressure wound therapy (NPWT) &conventional wound
      dressings in the open fracture wounds.
AB  - OBJECTIVE: Successful closure is a primary step of treatment in open fracture
      wounds. Delayed healing or complications can lead to increased treatment
      duration, costs and disability rates. The aim of this study was to compare
      Negative Pressure Wound Therapy (NPWT) and conventional wound dressings in
      patients with open fracture wounds. METHODS: In a prospective randomized clinical
      trial study, 90 patients with open fractures that were referred for treatment
      were enrolled between February 2013 to March 2015. Patients were divided into two
      groups. Group I underwent NPWT and group II underwent conventional wound
      dressing. Then patients were followed up for one month. Within the one month, the
      number of dressing change varied based on the extent of the wound. Duration of
      wound healing, presence of infection and the number of hospitalization days in
      these patients were recorded and compared at the end of the study between the two
      groups. Questionnaires and check lists were used to collect data. Analysis was
      done with SPSS 20, paired sample T-test, and chi-square tests. P<0.05 was
      considered significant. RESULTS: There was a significant difference between the
      rate of wound healing in the group one or NPWT group and group II (conventional
      wound dressings) P<0.05. There was no significant difference between two groups
      in incidence of infection (P=0.6). CONCLUSION: Using NPWT expedites the healing
      process of extremity wounds. It is more economical and can be considered as a
      substitute for the treatment of extremity wounds.

PMID- 27022348
TI  - Renal Biopsy: A much needed tool in patients with Systemic Lupus Erythematosis
      (SLE).
AB  - BACKGROUND AND OBJECTIVE: Systemic lupus erythematosis (SLE) is an inflammatory
      disorder associated with significant morbidity and mortality. Kidneys are
      frequently affected in SLE and various stages of lupus nephritis have been
      identified based on severity of the disease. Treatment varies with the staging
      and correct diagnosis is essential for timely intervention as it can have
      significant impact on morbidity and mortality. The objective of the study was to
      determine whether laboratory parameters of lupus nephritis (LN); including
      urinalysis, serum creatinine (S. Cr) and 24 hours urine protein can accurately
      predict histologic staging of the disease. METHODS: This retrospective study was
      conducted in department of Nephrology, Liaquat National Hospital Karachi from
      January 2012 to December 2014. Fifty one patients of SLE who underwent renal
      biopsy were selected. Patients, urinalysis at the time of renal biopsy, serum
      creatinine and 24 hours urine collection for protein were noted. All patients
      renal biopsy was read by the same pathologist. Patients were clinically staged
      based on these parameters and their histologic staging based on biopsy findings
      were compared, to see their correlation. Data was analyzed using SPSS version 17.
      Chi-square test was used to analyze categorical data and p<0.05 was considered
      significant. Cohen's kappa (kappa) analysis was used to examine the agreement by
      comparing lupus nephritis staging done by laboratory and histological ground. P
      value <0.05 indicates that agreement was unlikely due to chance alone. RESULTS:
      Among 51 patients analyzed, 37 patients were females (72.5%) and 14 patients were
      males (27.5%) with mean age of 32.51 + 16.91 years. In stage II, kappa (kappa) of
      0.304 represented fair strength of agreement and a p value of 0.012 (p<0.05)which
      was statistically significant. In stage III, kappa was 0.209 indicating none to
      slight agreement and a p value of 0.131 (p>0.05). In stage IV, kappa (kappa) was
      0.141 (slight agreement)and p value 0.301 (p>0.05) in stage V; kappa (kappa) of
      0.030 represented poor agreement and a p value of 0.828 (p>0.05). CONCLUSION:
      Staging of lupus nephritis done on basis of laboratory findings did not correlate
      well with underlying histological staging. Therefore, renal biopsy is an
      essential tool in approach to lupus nephritis in order to provide timely and
      appropriate treatment to patients.

PMID- 27022349
TI  - Effect of trimetazidine on heart rate variability in elderly patients with acute
      coronary syndrome.
AB  - BACKGROUND AND OBJECTIVE: Trimetazidine has mainly been used in coronary
      insufficiency, angina and elderly myocardial infarction. However, the effect of
      trimetazidine on the efficacy, heart rate variability (HRV) and protection of
      myocardial ischemia in elderly patients with acute coronary syndrome (ACS)
      remains unclear. This study aimed to investigate the effect of trimetazidine on
      the efficacy HRV and protection of myocardial ischemia in patients with ACS.
      METHODS: One hundred twenty two elderly ACS patients who were above 70 years were
      chosen and randomly divided into two groups. One group was given conventional
      therapy, such as aspirin, isosorbide mononitrate and fluvastatin, and the other
      group was administered trimetazidine in addition to conventional therapy. The
      treatment period was eight weeks. A PI-2.22B three-channel AECG system was used
      on every patient for 24 hour dynamic electrocardiogram monitoring and HRV
      analyses on the first day after admission and eight weeks after treatment. HRV,
      24 hour RR intermediate stage standard deviation (SDNN), five minutes average
      normal cardiac cycle standard deviation in 24 hour (SDANN), 24 hour close
      together normal cardiac cycle difference value mean square root (rMSSD), the
      percentage of difference of close together RR intermediate > 50 ms account total
      RR intermediate (PNN50), high frequency (HF) and low frequency (LF) parameters of
      patients were observed before and after treatment. RESULTS: The SDNN, SDANN,
      rMSSD, PNN50 and HF parameters significantly increased compared with the
      conventional treatment group (all P < 0.05). LF and LF/HF were significantly
      decreased in the trimetazidine treatment group compared with those in the
      conventional treatment group (all P < 0.05). CONCLUSION: Trimetazidine improves
      HRV of elderly ACS patients and reduces cardiovascular events.

PMID- 27022350
TI  - Frequency and pattern of congenital heart defects in a tertiary care cardiac
      hospital of Karachi.
AB  - OBJECTIVE: To determine the current frequency and pattern of distribution of
      congenital heart defects (CHD) at National Institute of Cardiovascular Diseases
      (NICVD), with the age at which initial diagnosis of CHD was made and the age at
      which the participant first visited the study center. METHODS: This is a
      descriptive and prospective hospital based study conducted in the pediatric
      cardiology unit outpatient department of NICVD. This study included all the
      patients, irrespective of age, having confirmed diagnosis of CHD on the basis of
      echocardiographic report. The collected data was entered and analyzed by using
      Statistical Package for Social Sciences v 20.0. RESULTS: Out of 1100 cases of
      congenital heart defects 1003 could be analyzed. There are 565 males (56.3%) and
      438 females (43.6%). Total 609 cases (60.6%) were of simple acyanotic lesions and
      387 (38.6%) were complex cyanotic lesions. In simple lesions septal defects
      constitute 64.9% and obstructive lesions were 11.0%. Tetralogy of fallot(TOF) was
      the commonest CHD and cyanotic lesion accounted for 24.4% of the total 1003 cases
      followed by Ventricular septal defect (VSD) 21.5%, Atrial septal defect (ASD)
      9.3% and Patent ductus arteriosus (PDA) 8.6%. Pulmonary stenosis(PS) was the most
      common obstructive lesion making 3.1% of the CHD. In 147 (14.5%) cases
      combination of simple defects were encountered and the commonest combination was
      ASD with VSD in 34 cases. CONCLUSION: Congenital Heart Defects are very common in
      our setup and early detection of CHD is increasing. Overall burden of CHD is also
      increasing therefore a proper population based study on a large scale is needed
      to estimate the prevalence accurately.

PMID- 27022351
TI  - Levels of empathy among undergraduate physiotherapy students: A cross-sectional
      study at two universities in Istanbul.
AB  - OBJECTIVE: The aim of this study is to determine differences of levels of empathy
      among undergraduates in each year of their four-year programs of physiotherapy.
      METHODS: During the 2014-2015 academic school year, 381 physiotherapy students
      were enlisted from two universities in Istanbul, one a foundation and the other a
      government university. The Turkish version of the Jefferson Scale of Physician
      Empathy was administered. Students were asked to indicate interest in particular
      physiotherapy specialties as well as their region of origin in Turkey. The
      Kruskal-Wallis analysis was used to determine differences among the four study
      years, and also to measure relationships between specialty interest, home-region,
      and empathy scores of the students. Empathy scores were also compared according
      to gender. RESULTS: The difference of empathy scores between the students of the
      two universities was borderline significant (p=0.057). Empathy scores in both
      universities increased to a significant degree after school entrance and
      decreased in the final year. Levels of empathy did not change according to
      gender, specialty interest, or home-region (p=0.722, 0.524, and 0.309,
      respectively). CONCLUSIONS: This study points to the need for physiotherapy
      curricula that would enhance empathy and give students practice in exhibiting
      this valuable attribute. Additional studies are needed that would include larger
      study populations and track the same students year by year as to how and why
      their empathy levels change during their training.

PMID- 27022352
TI  - Frequency of Stillbirths in a Tertiary Care Hospital, Karachi.
AB  - BACKGROUND AND OBJECTIVE: Pakistan accounts for the highest stillbirth rate in
      the world. Therefore, this observational study was planned to determine the
      prevalence of stillbirths and its associated demographic characteristics in the
      given context. Hence our objective included: To determine the frequency of
      stillbirths with reference to parity and gestational age in a tertiary care
      public hospital, Karachi. To determine the socio-demographic characteristics of
      families with stillbirths. METHODS: All pregnant mothers who delivered stillbirth
      babies at Gynaecology and Obstetrics ward of Jinnah Postgraduate Medical Center,
      Karachi a tertiary care facility were prospectively enrolled from October 2012 to
      September 2013. Deliveries occurred before 28 weeks of gestational age were
      excluded. Gestational age was confirmed from hospital record and attending
      physicians. Data was collected on predesigned proforma and analyzed using
      descriptive statistics. RESULTS: Among 7708 registered deliveries, 137 were
      stillbirths. A total of 84 mothers were primiparous and 12% of mothers were below
      20 years at the time of delivery. Majority of stillbirths were macerated type
      (80.3%) and 20% were fresh stillbirth. About 55% of still births occurred between
      33-37 weeks and 20% between 28-32 weeks. Almost 80% (109) of stillbirths were low
      birth weight and only 20% (28) were normal birth weight. CONCLUSION: This study
      shows that stillbirths are more common in primiparous mothers in a given context.
      Conducting awareness sessions with special focus on antenatal and obstetrical
      care of primiparous may be helpful to reduce still births.

PMID- 27022353
TI  - Effects of error on dose of target region and organs at risk in treating
      nasopharynx cancer with intensity modulated radiation therapy.
AB  - OBJECTIVE: To measure setup error of head and neck neoplasm in radiotherapy and
      discuss over effects of error on physical dose acting on target region and organs
      at risk of nasopharynx cancer (NPC) patients treated with intensity modulated
      radiation therapy (IMRT). METHODS: A total of 152 patients who developed head and
      neck neoplasm and received IMRT were randomly selected. Through comparing digital
      portal image and digital reconstruction image, we measured setup error,
      calculated expanding margin from clinical target volume (CTV) to planning target
      volume (PTV) and analyzed whether there was rules between setup error and
      treatment time. Additionally, 20 cases of NPC were selected. Three-dimensional
      error was simulated in planning system. Dose distribution was recalculated and a
      series of dose parameters of target volume and OAR were analyzed. RESULTS: Setup
      error in left-right, head-feet and ventral-dorsal direction was (-0.62+/-1.46)
      mm, (-0.41+/-1.54) mm and (-0.31+/-1.67) mm respectively. Regarding limit value,
      the maximum and minimum value in left-right direction, head-feet direction and
      ventral-dorsal direction was 2.70 mm and -6.00 mm; 3.00 mm and -5.00 mm, 5.00 mm
      and -7.50 mm. Expanding margin from CTV to PTV was 2.26 mm, 1.88 mm and 1.97 mm
      in left-right direction, head-feet direction and ventral-dorsal direction.
      CONCLUSION: During IMRT, only when setup error is controlled below 3 mm can
      sharply reduce the damage caused by radiation to normal tissue; therefore,
      quality security and control of electronic portal imaging device need (EPID) to
      be improved.

PMID- 27022354
TI  - Surgical audit of outcome of rhegmatogenous retinal detachment repair at
      Vitreoretinal unit JPMC in year 2014.
AB  - OBJECTIVE: To investigate the outcome of rhegmatogenous retinal detachment repair
      at Vitreoretinal unit of Jinnah Post Graduate Medical Centre Karachi in year
      2014. METHODS: One hundred and three eyes of one hundred and three patients, who
      underwent three ports parsplana vitrectomy + band + silicone oil, three ports
      pars plana vitrectomy + silicone oil, three ports pars plana vitrectomy + C3F8
      for rhegmatogenous retinal detachment (RRD) repair, at Jinnah Post Graduate
      Medical Centre, were included in this observational prospective study. Parsplana
      vitrectomy was done using 23G vitrectomy system. Duration of study was one year.
      Removal of silicone oil (ROSO) was done on the basis of completely flat retina at
      least for eight weeks or because of complications due to silicone oil. Patients
      were followed up post operatively on day one and after one week and then at four
      weekly interval till the end of the study. RESULTS: Anatomical success was
      achieved in 91 eyes (88.3%). However in 12 eyes (11.7%) retina redetached after
      removal of silicone oil. Functional success achievement of visual acuity of 3/60
      or better was achieved in 85 (82.5%) of eyes post operatively after removal of
      silicone oil or absorption of gas C3F8 as the case may be. CONCLUSION: Re
      detachment is common after removal of silicone oil and incidence of re-detachment
      is related to the degree of preoperative PVR and location of breaks. Re
      detachment occurs more commonly if the breaks are inferiorly located as compared
      to the superior ones.

PMID- 27022355
TI  - Neutrophil to lymphocyte ratio might help prediction of acute myocardial
      infarction in patients with elevated serum creatinine.
AB  - BACKGROUND AND OBJECTIVE: Diagnostic performance of troponin assays is affected
      by renal insufficiency. Neutrophil to lymphocyte ratio(NLR) is an independent
      predictor of acute coronary syndrome. Our objective was to evaluate performance
      of NLR in diagnosing acute myocardial infarction (AMI) among patients with
      elevated serum creatinine. METHODS: Patients with elevated creatinine levels
      evaluated for coronary artery disease were included (n=284). Patients were
      divided into two groups according to having AMI or non-specific chest pain. AMI
      diagnosis was made based on clinical and laboratory data, including serial EKG
      and cardiac enzymes, ECHO and coronary angiography. RESULTS: Troponin,
      neutrophil, and NLR were found to be higher in patients with AMI, compared to
      patients without AMI (P= 0.001, P= 0.001 and P=0.028, respectively). ROC curve
      analysis for NLR in diagnosing AMI was significant (AUC: 0.607; P=0.003).
      Sensitivity, specificity, LR +, LR-, PPV and NPV for NLR>7.4 were found as 42.3%,
      74.7%, 1.68%, 0.77%, 77% and 40%, respectively. Logistic regression analysis
      revealed that patients whose NLR>7.4 were 2.18 times as likely to have AMI.
      CONCLUSIONS: NLR can be used as an independent predictor of AMI in patients with
      renal insufficiency. This seems to get more important in the era of high
      sensitivity troponin assays. Our results might also help in early diagnosis of
      AMI in this high risk population while serial cardiac enzyme results are pending.

PMID- 27022356
TI  - Thyroid dysfunction in Khyber Pakhtunkhwa, Pakistan.
AB  - OBJECTIVES: The objective of this research was to elucidate some of the major
      relation of thyroid dysfunctions, keeping in view the various selected
      demographic details of included patients. METHODS: This study was approved by the
      ethical committee of Post Graduate Medical Institute (PGMI) Hayatabad Medical
      Complex Peshawar, and was conducted in the Institute of Radioactive Nuclear
      Medicine (IRNUM) Peshawar. The blood samples were collected, followed by their
      analysis for triiodothyronine (T3), tetraiodothyronine (T4) and thyroid
      stimulating hormone (TSH). RESULTS: The results obtained regarding the
      demographical aspects of the patients revealed that female gender has
      categorically significantly high percentage of occurrence of thyroid abnormality
      as compared to male gender (75.8% vs. 24.2%). Results regarding locality
      distribution of the patients depicted that majority of those belonged to the
      local population of Peshawar and Charsadda region. CONCLUSION: In Pakistan
      especially Khyber Pakhtunkwa (KPK), thyroid diseases are more common in females
      as compared to males. The most probable causes could be lactation and pregnancy.

PMID- 27022357
TI  - Post-infectious and non post-infectious irritable bowel syndrome: A comparative
      study.
AB  - OBJECTIVE: To compare the post-infectious irritable bowel syndrome (PI-IBS) and
      none post-infectious irritable bowel syndrome (NPI-IBS) clinically and
      experimentally. METHODS: From May 2013 to January 2015, eighty-nine patients with
      irritable bowel syndrome (IBS)were recruited in the internal department of the
      affiliated hospital of Shandong University of Traditional Chinese Medicine. The
      clinical data were collected for all the patients, and a blood sample was
      collected to detect the level of C-reactive protein (CRP) and intestinal fatty
      acid binding protein (IFABP), an investigation questionnaire of gastrointestinal
      symptom rating scale (GSRS) and self-rating anxiety scale (SAS) were carried out
      to evaluate the gastrointestinal function and anxiety status. RESULTS: In the
      study, forty-eight patients were included in PI-IBS group and 41 in Non-PI-IBS
      group. There was no significant difference in age, gender and GSRS between the
      two groups (p>0.05). In PI-IBS group 70.8% patients presented with the primary
      symptom of diarrhea and 60.4% presented with a SAS scores over 50, but in Non-PI
      IBS group, the values were only 19% (p<0.05) and 34.1% (p<0.05). The level of
      IFABP and CRP were significantly higher in PI-IBS group than those in Non-PI-IBS
      group (p<0.05). CONCLUSION: The PI-IBS may be different from Non-PI-IBS in
      mechanism and should be treated using different strategies.

PMID- 27022358
TI  - A heartrending burden of gynaecological cancers in advance stage at nuclear
      institute of medicine and radiotherapy Jamshoro Sindh.
AB  - OBJECTIVES: In Pakistan gynaecological cancers are among the leading causes of
      women's morbidity and mortality posing huge financial burden on families,
      communities and state. Due to lack of national cancer registry exact facts and
      figures are unknown therefore this study was planned to find out prevalence, age,
      site and stage of presentation of gynaecological cancers at Nuclear Institute of
      Medicine and Radiotherapy (NIMRA), Jamshoro. METHODS: A retrospective, cross
      sectional study was conducted from 1(st) January 2011 to 31(st) December 2011 at
      NIMRA Jamshoro. All cases of genital tract cancers were evaluated, required data
      was entered on predesigned performa and results were analyzed manually. RESULTS:
      Out of 2401 total registered cancer cases, 231 (9.6%) patients were suffering
      from gynaecological cancer making it third most common cancer. Ovary was
      commonest site followed by cervix and uterus. More than 60% cases presented in
      advanced stage, mostly during 4(th) and 5(th) decade of life. CONCLUSION:
      Gynecological cancer was among top three cancers at one of the busiest public
      sector cancer institute in Sindh province and significant number presented in
      advance stage making treatment difficult and expensive. There is urgent need for
      development and implementation of an effective health policy regarding cancer
      prevention and treatment.

PMID- 27022359
TI  - Efficacy of dexamethasone on postoperative analgesia in children undergoing
      hypospadias repair.
AB  - BACKGROUND AND OBJECTIVE: Management of post operative pain in children
      undergoing hypospadiasis repair, accounts for optimized surgery outcomes and
      improved patients' satisfaction. Thus, various studies have widely investigated
      the best approaches for the pain management. In this study our aim was to
      determine the effect of dexamethasone in combination with penile nerve block on
      the postoperative pain and complications in the children undergoing hypospadias
      surgery. METHODS: In this randomized double-blind placebo controlled trial, after
      obtaining informed consent from parents or legal guardians, 42 children
      undergoing surgical treatment of hypospadias were randomized in two groups to
      receive either IV dexamethasone 0.5 mg/kg (n=23) or placebo (normal saline)
      (n=19) during the operation. Penile block was performed in both groups using
      Bupivacaine 0.5% (1mg/kg) at the end of the procedure. By the end of the
      operation, FLACC (Face, Leg, Activity, Cry, Consolability) pain score was
      assessed as the primary outcome of the study. Secondary outcomes includes timing
      and episodes of rescue medication consumption, post operative nausea ?vomiting
      and bleeding. All the outcomes were assessed in the recovery room and after 2, 6,
      12, and 24 hours. RESULTS: The median of FLACC pain scores at the recovery room
      and 2, 6, 12, and 24 hours post operation was 2, 1, 1, 1, and 2 for the
      dexamethasone group and 8, 8, 7, 7, and 8 for the placebo group respectively.
      This were significantly different (P<0.000). The median time of first rescue
      medication consumption was 8 hours post operation for the dexamethasone group and
      three hours for the placebo group which was significantly different (z= 4.57,
      p<0.000). The maximum episode of post operative rescue medication consumption in
      dexamethasone group was 4 episodes in only one patient and the minimum was one
      episode in 11 patients. In comparison numbers in placebo group were five episodes
      in seven patients and three episodes in four patients. The result indicated that
      there was statistically significant difference between two groups in terms of
      episodes of rescue medication consumption (Chi2= 31.4, p<0.000). CONCLUSION:
      Single dose of intravenous dexamethasone (0.5 mg/kg) in combination with penile
      block decreased the post operative pain measures, and total post operative
      analgesic requirement. It also increased the onset of the first analgesic
      requirement compared to penile block alone.

PMID- 27022360
TI  - Effect of intralesional 5 fluorouracil injection in primary pterygium.
AB  - OBJECTIVE: To determine mean change in visual acuity, corneal astigmatism and
      clinical appearance of pterygium after intralesional injection of 5-Fluorouracil.
      METHODS: This was a Quasi experimental study conducted at Armed Forces Institute
      of Ophthalmology, Rawalpindi, Pakistan from June 2014 to May 2015. Total 68 eyes
      of 54 patients were included in the study. Patients were treated by injecting 0.1
      ml of 5-FU (5mg) weekly injections for 04 weeks. All the patients underwent
      ophthalmic clinical examination that included Uncorrected distant visual acuity
      (UCVA), corrected distant visual acuity (CDVA), keratometery with Auto Ref
      keratometer (RK-F1, Canon) and slit lamp examination before and 04 weeks after
      the last injection. RESULTS: Total 68 eyes of 54 patients (18 females and 36
      males) were treated with intralesional injection of 5 FU. Out of total, 30 were
      right eyes while 38 were left eyes. Age of patients ranged from 23 to 53 years
      with mean age of 39.2 +/- 4.90 years. Mean UCVA and corneal astigmatism before
      treatment were 0.162 +/- 0.167 and 2.12 +/- 1.53 respectively while the same
      parameters 04 weeks after last injection of 5 FU were 0.166 +/- 0.168 and 1.92+/
      1.45 respectively. The magnitude of induced change in astigmatism was (0.235 +/-
      1.35). Ninety seven percent of the patients showed improvement in clinical
      appearance. CONCLUSION: Intralesional 5-FU injection results in significant
      clinical and cosmetic improvement of primary pterygium.

PMID- 27022361
TI  - Analysis of surgeries for Degenerative lumbarstenosis in elderly patients.
AB  - OBJECTIVE: To analyze the effect of decompression alone and combined
      decompression, fusion and internal fixation procedure for degenerative lumbar
      stenosis in elderly patients. METHODS: We reviewed 168 lumbar stenosis patients
      treated using decompression alone or with combined procedures in the department
      of orthopaedics of Tianjin 4(th) Centre Hospital from October 2010 to January
      2014. The clinical data including age, gender, procedure type, operation time,
      follow-up period, blood loss, preoperative and postoperative JOA and ODI scores
      were recorded. The patients were divided into decompression alone group and
      combined surgeries group according to the procedure type. RESULTS: The combined
      surgeries group presented with larger blood loss (p<0.05) and more operation time
      (p<0.05), compared with the group of decompression alone. The preoperative and
      postoperative JOA scores were significantly higher (p<0.05), and the ODI scores
      significantly lower in the decompression alone group (P<0.05), but at the final
      follow-up, there were no significant difference between the two groups (p>0.05).
      The complication rate was lower in the group of decompression alone, but there
      was no significant difference between the two groups (p>0.05). CONCLUSION: Both
      the decompression alone and combined surgeries can result in a satisfactory
      effects in elderly patients with degenerative lumbar spinal stenosis, but the
      combined surgeries presented with a relatively higher complication rate.

PMID- 27022362
TI  - Frequency and risk factors of low birth weight in term pregnancy.
AB  - OBJECTIVE: To determine frequency of Low Birth Weight (LBW) at term and to
      determine frequency of various associated risk factors. METHODS: This cross
      sectional study was conducted in Department of Obstetrics and Gynaecology Layari
      General Hospital and Dow University of Health Sciences Karachi between January
      2007 to July 2008. Women with singleton pregnancy of 37 and above completed weeks
      were identified. Those women who gave birth to babies with less than 2500gm were
      recruited in the study. In all those patients who gave birth to LBW babies risk
      factors were assessed. The variables including age, parity, booking status,
      maternal weight and height, socioeconomic condition, smoking, fetal gender and
      birth weight were noted on a questionare. The data was analyzed on SPSS Version
      15. Frequency of LBW and its associated risk factors were determined. RESULTS:
      During study period 10.6% patients delivered LBW babies. Antenatal care was not
      received in 67% patients. Parity was less than three in 87%. In 26% of patients
      maternal weight was less than 50 kg and in 37% patients with LBW, maternal height
      was less than five feet. Majority of patients were anaemic (72%) including 20%
      with haemoglobin < 7 grams. CONCLUSION: LBW is associated with a group of factors
      which may be regarded as high risk factors. These include low socio economic
      status, anaemia, primiparity, short maternal height and less than average weight.

PMID- 27022363
TI  - Virulence factors of Candida species isolated from patients with urinary tract
      infection and obstructive uropathy.
AB  - OBJECTIVE: Fungal urinary tract infections due to Candida have increased
      significantly in recent years. Our research objective was to study Candida
      species in urine samples of patients with urinary tract infections (UTIs)
      associated with obstructive uropathy and to investigate the virulence factors of
      the isolated Candida. METHODS: Patients were divided into two groups: Group I
      (cases): 50 patients with UTIs and obstructive uropathy. Group II (control): 50
      patients with UTIs but with no functional or anatomical obstruction of their
      urinary tract. Clinical histories and physical examinations, together with
      laboratory investigations of urine samples were carried out in all patients in
      this study. Mid stream urine samples were examined microscopically and by fungal
      cell culture. The isolated Candida species were identified by analytical profile
      index (API). Candida Virulence factors were determined for the isolated Candida.
      The susceptibility to fluconazole was evaluated. RESULTS: This study revealed an
      overall isolation rate of 27% of Candida species among all patient groups. The
      rate was 36% in cases, and 18% in controls, a difference found to be
      statistically significant (P<0.05). By API, C.albicans was detected in 44% of
      Candida species in cases, and in 33% in controls. While C.glabrata was detected
      in 28% of Candida species in cases, and in 22% in controls. C.tropicalis was
      detected in 17% of Candida species in cases, and in 22% in controls. Both
      C.krusei and C.kyfr were detected in 5.5% of Candida species in cases, and in 11%
      in controls. In terms of virulence factors the study showed that 11 out of 27
      (40.5%) of Candida isolates were biofilm positive by tube adherence.
      Phospholipase activity was demonstrated in 12 out of 27 (44.5%) of Candida
      isolates. Secretory aspartic proteinase activity was demonstrated in 13 out of 27
      (48%) of the Candida isolates. CONCLUSION: Candida is an important cause of UTIs
      and obstructive uropathy is a major predisposing factor.

PMID- 27022364
TI  - The effect of anaesthesia technique on caesarean section.
AB  - OBJECTIVE: When conducting a caesarean section under regional anaesthesia, either
      epidural anaesthesia or spinal anaesthesia can be used. Patients who underwent
      caesarean section in our hospital were surveyed retrospectively to confirm and
      compare the merits and demerits of spinal anaesthesia and epidural anaesthesia to
      determine the most efficient approach. METHODS: Mothers meeting the American
      Society of Anesthesiologists physical status classification system (ASA) I or II,
      who underwent caesarean sections at our hospital were surveyed retrospectively.
      The survey targeted one hundred patients each who received spinal anaesthesia and
      epidural anaesthesia. The time from anaesthesia to surgical incision (A to S
      time), entire anaesthesia time, and the usage of vasopressor and midazolam were
      compared according to anaesthetic approach. RESULTS: The A to S time and the
      entire anaesthesia time of the group that underwent spinal anaesthesia were
      significantly short compared to the times recorded for the group who underwent
      epidural anaesthesia, and the use of vasopressor was more frequent in the spinal
      anaesthesia group because their blood pressure decline was larger. CONCLUSION:
      The A to S time and the entire anaesthetic time were longer for epidural
      anaesthesia than for spinal anaesthesia. However, the haemodynamic change was
      smaller and vasopressor was hardly used in the former group. Therefore, the
      choice of the technical method will depend on the clinical, anaesthetic, and
      obstetric situation.

PMID- 27022365
TI  - Research design and statistical methods in Pakistan Journal of Medical Sciences
      (PJMS).
AB  - OBJECTIVE: This article compares the study design and statistical methods used in
      2005, 2010 and 2015 of Pakistan Journal of Medical Sciences (PJMS). METHODS: Only
      original articles of PJMS were considered for the analysis. The articles were
      carefully reviewed for statistical methods and designs, and then recorded
      accordingly. The frequency of each statistical method and research design was
      estimated and compared with previous years. RESULTS: A total of 429 articles were
      evaluated (n=74 in 2005, n=179 in 2010, n=176 in 2015) in which 171 (40%) were
      cross-sectional and 116 (27%) were prospective study designs. A verity of
      statistical methods were found in the analysis. The most frequent methods
      include: descriptive statistics (n=315, 73.4%), chi-square/Fisher's exact tests
      (n=205, 47.8%) and student t-test (n=186, 43.4%). There was a significant
      increase in the use of statistical methods over time period: t-test, chi
      square/Fisher's exact test, logistic regression, epidemiological statistics, and
      non-parametric tests. CONCLUSION: This study shows that a diverse variety of
      statistical methods have been used in the research articles of PJMS and frequency
      improved from 2005 to 2015. However, descriptive statistics was the most frequent
      method of statistical analysis in the published articles while cross-sectional
      study design was common study design.

PMID- 27022366
TI  - Influence of psychological intervention on pain and immune functions of patients
      receiving lung cancer surgery.
AB  - OBJECTIVE: To observe the influence of psychological intervention on pain, immune
      system and adrenocortical functions of patients receiving lung cancer surgery.
      METHODS: We selected 124 patients who received surgery for treating stage I or II
      lung cancer and divided into experimental group and control group. The
      experimental group received comprehensive psychological intervention while the
      control group was given conventional nursing intervention. Pain of patients in
      two groups was evaluated by visual analog scale (VAS). Before and after
      intervention, CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+) and free cortisol level in
      serum were measured. Moreover, QLQ-C30, a life quality measurement scale
      developed by European Organization for Research and Treatment of Cancer (EORTC)
      was used. RESULTS: Compared to control group, VAS of patients in experimental
      group remarkably decreased before anesthesia, 6 hour, 12 hour 24 hour and 48 hour
      after surgery (P<0.05), and moreover, OLQ-C30 score and various factor scores
      (except physical symptoms) in experimental group were much higher (P<0.05). No
      statistical significant difference was found in immune index between two groups
      before intervention (P>0.05). Differences of CD3(+) and CD4(+) before and after
      intervention were both statistically significant (P<0.05), so did free cortisol
      level (P<0.05). CONCLUSION: Comprehensive psychological intervention can
      effectively relieve pain, improve immune functions and enhance quality of life
      for patients suffering from lung cancer surgery.

PMID- 27022367
TI  - Correlation of CD24 expression with histological grading and TNM staging of
      retinoblastoma.
AB  - OBJECTIVE: Correlation of CD24 expression with histological grading and TNM
      staging of retinoblastoma. METHODS: This cross-sectional study was conducted in
      the Department of Pathology, BMSI, JPMC and NICH from 1(st) January 2009 to
      31(st) December 2013. A total 68 diagnosed cases of retinoblastoma were selected
      for CD24 immuno staining. The data was analyzed by using SPSS version 22.
      RESULTS: Out of 68 cases 7.35% showed grade 1 followed by 11.76% in G2, 26.47% in
      G3 and 54.41% in G4. Majority of cases i.e. 60.29% in stage IV followed by 19.11%
      in stage I, 10.29% each in stage II and stage III. CD24 immuno staining
      positivity was seen in majority of grade 3 and grade 4. In grade 3, 38.88% showed
      moderate and 22.22% strong immuno reaction. Amongst grade 4, 40.54% showed
      moderate and 13.51% strong positive. Variable immuno pattern was observed
      according to TNM staging. In stage I, 46.15% showed moderate and 7.69% strong
      positivity, while in stage II, 57.14% were negative for saining. In stage III,
      42.85% were negative while 28.57% each showed moderate and strong staining.
      Majority of cases in stage IV i.e. 48.78% were negative for staining while
      34.14%, 17.07% showed moderate and severe CD24 immuno staining. CONCLUSION:
      Majority of grade I retinoblastoma were in TNM stage I & II and mostly were
      immuno negative. Lymph node and distant metastatic cases were 75% in G4 and 25%
      in G3, all of them showed moderate to strong immunoreactivity. These results
      showed that CD24 expression may be a marker of poor prognosis in retinoblastoma.
      Whereas TNM staging of retinoblastomas with CD24 expression had varying pattern
      and showed no significant correlation between them.

PMID- 27022368
TI  - The information requirements and self-perceptions of Turkish women undergoing
      hysterectomy.
AB  - OBJECTIVES: To investigate the affects, information requirements and self
      perceptions of Turkish women undergoing hysterectomy. METHODS: A descriptive
      cross-sectional study was conducted on 37 Turkish women undergoing hysterectomy
      and followed in a gynecology unit of a state hospital in Canakkale, Turkey,
      between February and August 2012. Data were collected before discharge with a
      questionnaire composed of 32 questions. Percentage distributions and Chi-square
      test were used in the evaluation of the data. RESULTS: There was a significant
      relationship between fear of anesthesia and number of pregnancies (p=0.007) and
      between death during surgery and number of pregnancies in the preoperative period
      (p=0.027). The relationship between knowing type of surgery and knowing when
      sutures would be removed was also significant in post-operative period (p=0.045).
      In addition, there was a significant relationship between women's living only
      with their husbands and worrying about not having children anymore (p=0.032).
      CONCLUSION: The women's information needs were high and women's self-perceptions
      had been affected negatively after hysterectomy. It is recommended that nurses,
      primarily health professionals should have adequate knowledge on comprehensive
      care and psychosocial support after hysterectomy.

PMID- 27022369
TI  - Frequency of Magnetic Resonance Imaging patterns of tuberculous spondylitis in a
      public sector hospital.
AB  - OBJECTIVE: To determine frequencies of different MRI patterns of tuberculous
      spondylitisin a public sector hospital in Karachi. METHODS: This descriptive
      multidisciplinary case series study was done from October 25, 2011 to May 28,
      2012 in Radiology Department and Department of Medicine in the Jinnah
      Postgraduate Medical Center Karachi. MRI scans (dorsal / lumbosacral spine) of
      the Patients presenting with backache in Medical OPD, were performed in Radiology
      Department. Axial and sagittal images of T1 weighted, T2 weighted and STIR
      sequences of the affected region were taken. A total of 140 patients who were
      diagnosed as having tuberculous spondylitis were further evaluated and analyzed
      for having different patterns of involvement of the spine and compared with
      similar studies. RESULTS: Among frequencies of different MRI pattern of
      tuberculous spondylitis, contiguous vertebral involvement was 100%, discal
      involvement 98.6%, paravertebral abscess 92.1% cases, epidural abscess 91.4%,
      spinal cord / thecal sac compression 89.3%, vertebral collapse 72.9%, gibbus
      deformity 42.9% and psoas abscess 36.4%. CONCLUSION: Contiguous vertebral
      involvement was commonest MRI pattern, followed by disk involvement,
      paravertebral & epidural abscesses, thecal sac compression and vertebral
      collapse.

PMID- 27022370
TI  - Effects of total thoracoscopic surgery on coronary artery fistulae complicated
      with ectasia.
AB  - OBJECTIVE: To compare the effects of thoracotomy and total thoracoscopic surgery
      on coronary artery fistulae complicated with ectasia. METHODS: Forty-six patients
      with coronary artery fistulae complicated with ectasia were randomly divided into
      a treatment group and a control group (n=23) which were given totally
      thoracoscopic surgery and thoracotomy respectively. Both groups were followed up.
      RESULTS: All patients survived the surgeries and were discharged from the
      hospital. The treatment group had significantly less intraoperative blood loss,
      earlier postoperative ambulation and shorter postoperative hospitalization stay
      more than those of the control group (P<0.05). The two groups had similar plasm
      cortisol and adrenocorticotropic hormone levels one day before and after surgery.
      These levels peaked on the postoperative 3rd day, but those of the treatment
      group were significantly lower (P<0.05). The two groups had similar left and
      right atrial diameters as well as left ventricular ejection fractions (LVEFs)
      before surgery, but the treatment group had significantly higher postoperative
      LVEF (P<0.05) as well as significantly smaller left and right atrial diameters in
      the postoperative 1st and 3rd months (P<0.05). The treatment group was
      significantly less prone to postoperative complications such as chest pain,
      atelectasis and pulmonary infection than the control group (P<0.05). CONCLUSION:
      Total thoracoscopic surgery promoted the recovery of coronary artery fistulae
      complicated with ectasia, improved cardiac remodeling and cardiac function, and
      alleviated stress reaction, with well-proved safety.

PMID- 27022371
TI  - Effectiveness of Constraint induced movement therapy as compared to bimanual
      therapy in Upper motor function outcome in child with hemiplegic Cerebral palsy.
AB  - OBJECTIVE: This study aims at determining the effectiveness of constraint induced
      movement therapy as compared to bimanual therapy for improving functional status
      in children with hemiplegic cerebral palsy. METHODS: This study was a randomized
      control trial, children (n = 20) with spastic hemiplegic cerebral palsy was
      randomly allocated to CIMT (constraint induced movement therapy) and BMT
      (bimanual therapy) group. The children with spastic hemiplegia, age between 1.5
      and 12 year and having 10 degrees of wrist extension and 10 degrees of finger
      extension were included in study. Treatment regime was two hours of daily
      training six days a week for two weeks. Constraint was applied to CIMT group for
      six hours. The outcome tool QUEST was used for baseline and post treatment
      assessment. RESULT: CIMT had superior outcome as compared to BMT in improving
      functional status (p=0.007). On QUEST tool grasp and dissociated movements
      results were significant (p=0.005) and (p=0.028) respectively. Weight bearing and
      protective extension resulted in no significant outcome (p=0.080) and (p=0.149)
      respectively. Dissociated movements and grasp are significantly improved but
      there is no difference for weight bearing and protective extension in CIMT
      treated group as compared to BMT treated group. CONCLUSION: CIMT approach is
      better in improving functional status of child with cerebral palsy as compared to
      BMT. Significant improvement in grasp and dissociated movement is noted in group
      of CIMT while there was no significant improvement in weight bearing and
      protective extension in CIMT group when compared to BMT. CIMT is considered the
      appropriate treatment approach for unilateral conditions while BMT for bilateral
      conditions.

PMID- 27022372
TI  - Evaluation of effectiveness of the using a pillow in children for dental
      rehabilitation under general anesthesia in term for facilitate intubation.
AB  - BACKGROUND AND OBJECTIVE: Airway safety may be provided with endotracheal
      intubation especially for oral procedures because of some potential risks such as
      aspiration of secretion or foreign bodies. In this study, we aimed to determine
      whether placing a pillow under the occiput may facilitate endotracheal intubation
      in non-cooperative children whose extensive dental treatments were planned to
      take place under general anesthesia. METHODS: The study was performed in Erciyes
      University, Faculty of Dentistry between March-July 2014. A total 150 ASA I-II
      children, between 3-9 years were included in this study. Pillow was folded under
      the occiput in Group 1 (n=75), patients lay on a flat surface in Group 2 (n=75)
      during the anesthesia induction and intubation period. RESULTS: There were no
      statistically significant differences between groups regarding the demographic
      data (age, weight, gender) (p>0.05). Operation times were similar in both groups
      (p=0.329). The number of intubation attempts was smilar in both groups (p=0.412).
      The intubation time was longer in group one than in group two (p= 0.025).
      CONCLUSION: We concluded that, placing a pillow under the patients occiput
      provided longer intubation time without changing the number of attempts in the
      normal airway in non-cooperative children whose extensive dental treatments were
      planned to take place under general anesthesia.

PMID- 27022373
TI  - Impact of Combined modular assessment on deep learning and personal development
      of medical students.
AB  - OBJECTIVE: To determine the effect of transition of summative assessment from
      frequent modular to combined block assessment and its role on learning of medical
      students. METHODS: A descriptive study was carried out at Islamic International
      Medical College. A questionnaire comprizing of 8 questions with Likert scale (1
      5) was designed for 3(rd) year students. The questions were grouped in three
      categories which included learning acquired, personal development and efficacy of
      assessment tools used in combined block assessment and frequent modular exam
      separately. Results of end of year exams were analyzed for difference in
      performance of students in two exams. The received data was analyzed by using
      SPPS 21. RESULTS: About 60% students agreed that they need to study regularly in
      frequent modular exams. Combined block assessment promoted more indepth studies
      and multiple revisions 51% and 55% students respectively. About 42% students, in
      comparison with 33%, agreed that CBA helped in their personal development while
      42% students agreed to assessment tools used in CBA while only 28% students to
      those used in frequent modular exam. About 47% students agreed that assessment
      tools in CBA were useful for deep learning and 47% students agreed that time
      given in CBA was enough in exam preparation. Comparison of all results (x 2
      tests) was statistically significant. The comparison of end of year performance
      showed improvement in the mean of total marks obtained and decrease in the number
      of failed students in combined block assessment. CONCLUSION: Transition from
      frequent to combined block assessment with regular formative assessment has
      positive effect on learning, personal grooming and performance in summative
      assessment.

PMID- 27022374
TI  - Relationship of anxiety and burnout with extrasystoles in critical care nurses in
      Turkey.
AB  - OBJECTIVE: To determine the relationship between levels of anxiety and burnout
      and prevalence of atrial extrasystoles (AESs) and ventricular extrasystoles
      (VESs) among critical care nurses. METHODS: The sample of study included 51
      nurses who worked in the intensive care units of a university hospital located in
      western Turkey. Beck's Anxiety Inventory and the Maslach Burnout Inventory were
      used in the study. RESULTS: The mean emotional exhaustion score of the nurses was
      14.68+/-6.10, the mean personal accomplishment score was 19.19+/-7.08, the mean
      depersonalization score was 5.31+/-3.84 and the mean anxiety score was 12.37+/
      11.12. The rates of VESs and AESs detected in the critical care nurses were 21.6%
      and 35.3%, respectively. No relationship was found between levels of anxiety and
      burnout and the prevalence of AESs and VESs among the critical care nurses. A
      positive correlation was found between personal accomplishment scores and numbers
      of VESs (r= 0.693, p=0.001) and AESs (r= 0.700, p= 0.001). CONCLUSION: In the
      present study, there were low mean scores of burnout and anxiety among nurses
      working in intensive care units. No relationship was found between levels of
      anxiety and burnout and the prevalence of AESs and VESs among nurses who work in
      intensive care units. It was found that the people feeling more personal
      accomplishment have more VES or AES. The prevalence of AESs and VESs among the
      critical care nurses suffering from burnout and anxiety may be studied in the
      future studies.

PMID- 27022375
TI  - Post thrombolytic resolution of ST elevation in STEMI patients.
AB  - OBJECTIVE: To study the effect of timing of thrombolytic therapy, cardiac risk
      factors and site of infarction on S.T. resolution post thrombolysis in STEMI
      patients. METHODS: This was a descriptive hospital based study conducted at the
      Hayatabad Medical Complex Peshawar. The duration of our study was 5 months from
      February 2015 to June 2015. Diagnosis of STEMI in symptomatic patients was based
      on the ECG recognized. Definition of Myocardial Infarction. Time from onset of
      chest pain to presentation of patients in emergency was noted through history of
      patients along with time of streptokinase. ECG recordings of patients were taken
      upon presentation in Emergency. Serial ECG monitoring was done after
      administration of Streptokinase (SK). ST resolution was observed in the lead with
      the maximum ST elevation. Data were presented as frequencies and percentages, chi
      square test was applied. RESULTS: Among 83 patients with STEMI 50.6% were males
      and 49.4% were females with the age group range of 30-83 years. Fifty nine
      patients (71.08%) with STEMI underwent thrombolysis within 12 hours of onset of
      chest pain while 24 patients (28.92%), underwent thrombolysis after 12 hours of
      onset of chest pain. Out of the 59 patients who received thrombolytic therapy
      before 12 hours, 43 (72.88%)completely resolved, while those who received
      thrombolytic therapy after 12 hours none of them completely resolved as per ECG
      findings. By applying chi-square test it gives us value of 36.470, and p-value
      <0.001. In our study 28 patients were diabetic and out of these six (21.43%)
      completely resolved as per ECG post thrombolysis, 9 (32.14%) partially resolved
      and 13 (46.43%) failed to resolve. On the other hand, in non-diabetics out of 55,
      37 (67.27%) completely resolved, 12 (21.82%) partially resolved and 6 (10.91%)
      failed to resolve. Among 61 hypertensive, 26 (42.62%) had complete resolution and
      in 22 who were non-hypertensive, 17 (77.27%)had complete resolution on ECG.
      Hyperlipidemia and site of infarction didn't have statistically significant
      effect on the resolution of ECG post thrombolysis in STEMI patients. CONCLUSION:
      Patients with diabetes, hypertension and those who receive thrombolysis after 12
      hours of onset of chest pain respond poorly to thrombolytic therapy as per ECG
      findings whereas hyperlipidemia and site of infarction don't affect the response
      of STEMI patients to thrombolysis.

PMID- 27022376
TI  - Quality of an Informed Consent Prior to a Surgical Intervention? Experience of a
      Teaching Hospital.
AB  - OBJECTIVE: To determine how far the information given by the physicians for the
      informed consent prior to the surgical intervention is comprehended by the
      patients. METHODS: The study was carried out between July 1(st), 2012 and July
      1(st), 2013 at Gulhane Medical Faculty. A total of 400 patients, who were in the
      third postoperative day after various surgical procedures (orthopedics, urology,
      ophthalmology, plastic surgery and breast surgery), were included in the study.
      RESULTS: Of all the patients, 73.5% stated that the operative information was
      provided by physicians, whereas 22.7% claimed that no information was given in
      this regard. The patients who knew the name of the disease was 78%, while 18.3%
      did not know. Of all the patients, 25.7% knew the name of the operation, in
      contrast to of 52.3% who did not know it. About 12.5% of patients stated that
      they were not informed about the likely complications during the surgery, whereas
      13.7% of patients reported that they were not informed about the post-operative
      complications. CONCLUSION: The verbal information and the written texts,
      different approaches such as drawings and visual materials (i.e. video's and
      photographs) should be considered while providing information to the patients.
      While doing so the level of education of the community should also be taken into
      account.

PMID- 27022377
TI  - The outcome of combination of low dose oral prednisolone with propranolol for the
      treatment of infantile haemangioma.
AB  - OBJECTIVE: To determine the outcome of combination of low dose oral Prednisolone
      with oral propranolol for the treatment of infantile hemangioma. METHODS: The
      patients fulfilling the inclusion criteria were registered through outpatient
      department. Diagnosis was confirmed clinically and on Color Doppler
      ultrasonography (CD). All the patients were given oral prednisolone in a dose of
      1mg/kg/day and propranolol in a dose of 0.5mg/kg/day twice a day and increased up
      to 1.5mg/kg/day BID within three days with close monitoring of heart rate, blood
      pressure and blood glucose as inpatient. Treatment was given for three months
      then titered down for two weeks before cessation of treatment. The follow-up of
      patients were performed at 7(th) day, at 1(st) month and finally at 3(rd) month.
      Treatment compliance was checked during each visit along with outcome parameters
      i.e. response which was excellent, good, moderate slight improvement and no
      effect. All the information's were collected. Data was analyzed by using SPSS
      version 10. RESULTS: Out of total 73 patients, 36.99% (n=27) were one year of
      age, 32.88% (n=24) were two years of age and 30.13% (n=22) were three years of
      age, mean+/- SD: 1.96+/-0.54 years, 53.42% (n=39) were male and 46.58% (n=34)
      were females, frequency of response of the treatment was recorded as 56.16%
      (n=41) had excellent, 23.29% (n=17) had good, 15.07% (n=11) had moderate
      response, 4.11% (n=3) had slight improvement and 1.37% (n=1) had no effect while
      frequency of acceptable outcome revealed as acceptable in 79.45% (n=58) while
      20.55% (n=15) had not acceptable outcome. CONCLUSION: The frequency of acceptable
      outcome of combination of low dose oral Prednisolone with oral propranolol for
      the treatment of infantile hemangioma is higher.

PMID- 27022378
TI  - Effects of thyroid cystectomy for primary hyperparathyroidism on immune function.
AB  - OBJECTIVE: To evaluate the effects of thyroid cystectomy for primary
      hyperparathyroidism on immune function. METHODS: Ninety-two patients with
      parathyroid cysts complicated with primary hyperparathyroidism were randomly
      divided into a treatment group and a control group (n=46). The treatment group
      received endoscopic thyroidectomy through the anterior chest wall via the areolar
      approach, and the control group was treated with conventional open thyroidectomy.
      RESULTS: The two groups had similar immune function indices as well as thyroid
      hormone, serum calcium and phosphorus levels before surgery (P>0.05). After
      surgery, FT3 and FT4 levels significantly increased in both groups, whereas that
      of TSH significantly decreased (P<0.05). The levels of the two groups differed
      significantly on the postoperative 5th day (P<0.05). NK%, CD3+%, CD4+% and CD8+%,
      which significantly fluctuated on the postoperative 1st day in both groups
      (P<0.05), were basically recovered on the postoperative 5th day in the treatment
      group that had significantly different outcomes from those of the control group
      (P<0.05). On the postoperative 1st and 5th days, the treatment group had
      significantly lower serum calcium level and significantly higher serum phosphorus
      level than those of the control group (P<0.05). The surgeries were successfully
      performed for all patients. During three months of follow-up, the treatment group
      was significantly less prone to complications such as surgical site infection,
      recurrent laryngeal nerve injury, parathyroid crisis and hoarseness than the
      control group (P<0.05). CONCLUSION: For treatment of primary hyperparathyroidism,
      endoscopic thyroidectomy through the anterior chest wall via the areolar approach
      decreased the incidence rate of complications, as well as promoted the recovery
      of serum calcium and phosphorous levels, probably by only mildly affecting immune
      function and thyroid hormone levels.

PMID- 27022379
TI  - Effect of pan retinal photocoagulation on central macular thickness and visual
      acuity in proliferative diabetic retinopathy.
AB  - OBJECTIVE: To evaluate the effect of pan-retinal photocoagulation with Pattern
      Scan Laser (pascal)on best corrected visual acuity and central macular thickness
      in patients having proliferative diabetic retinopathy (PDR). METHODS: This study
      was conducted at AFIO, Rawalpindi, Pakistan from Oct 2014 to Jul 2015. Sixty
      seven eyes of 46 patients having proliferative diabetic retinopathy were included
      in the study. All patients underwent ophthalmic clinical examination including
      uncorrected distant visual acuity (UCVA), best corrected visual acuity (BCVA),
      fundus examination with slit lamp and optical coherence tomography to document
      the pretreatment central macular thickness (CMT). Two sessions of PRP using
      Pattern Scan Laser were performed 04 weeks apart and OCT was repeated 04 weeks
      after the 2(nd) session. Central macular thickness and BCVA were documented.
      RESULTS: Sixty seven eyes of 46 patients (29 females and 17 males) with mean age
      of 57.45 +/- 5.78 years underwent treatment with two sessions of laser PRP. Mean
      pretreatment BCVA was 0.67 +/- 0.43 and mean post-treatment BCVA was 0.57 +/-
      0.3. Mean central macular thickness (CMT)as measured by OCT was 391.93 +/- 170.43
      before treatment and 316.91 +/- 90.42 um after treatment. The magnitude of
      induced change in CMT after treatment was 75.01 +/- 90.75 and BCVA was 0.09 +/-
      0.14. CONCLUSION: Laser PRP with Pattern scan laser alone in patients with
      combined presentation of PDR and DME is safe and effective.

PMID- 27022380
TI  - The results of photorefractive keratectomy with Mitomycin-C in myopia correction
      after 5 years.
AB  - OBJECTIVE: To evaluate the results of photorefractive keratectomy (PRK) with
      mitomycin C in myopia correction after five years. METHODS: This is a cross
      sectional study which included 145 eyes of 74 patients in 18 to 51 years age
      group that were undergoing Photorefractive keratectomy with mitomycin C using
      Allegretto Wave Eye-Q 400-Hz excimer laser platform in Markazi Eye Center,
      Tehran, Iran. All the surgical procedures were performed by the same surgeon.
      After five years follow-up evaluation including BCVA, UCVA, Refractive error
      measurement and external eye examination was performed. RESULTS: The mean diopter
      of spherical equivalent before surgery was -3.40+/-1.73. The following findings
      were obtained after 5 years follow up visit: The mean spherical equivalent value:
      -0.08+/-0.40, the mean: Log MARUCVA: 0.02+/-0.07, the mean Log MAR BCVA: 0.00+/
      0.04. CONCLUSION: PRK is an effective, safe and predictable method used to
      correct myopia. The wave front-optimized algorithm of the Allegretto Wave Eye-Q
      400-Hz excimer laser platform demonstrated good refractive and visual results.
      Presence of variables such as gender, age and astigmatism before operation have
      no significant impact on the result of this operation.

PMID- 27022381
TI  - Evaluation of knowledge of Health care professionals on warfarin interactions
      with drug and herb medicinal in Central Saudi Arabia.
AB  - OBJECTIVES: To evaluate health care professionals' knowledge on warfarin
      interactions with drugs and herbs. METHODS: A self-administered questionnaire was
      developed to assess health care professionals' knowledge on warfarin interactions
      with drug and herb. Respondents were asked to classify 15 drugs that may effect
      on warfarin action as "enhance", "inhibit ", "no effect". The study sample
      involved health care professionals (physicians, pharmacists and nurses) from king
      Salman hospital, Saudi Arabia. RESULTS: About 92.2% of health care professionals
      identified warfarin interactions with aspirin, 4.4% for warfarin and fluoxetine.
      Warfarin and cardiac agents (atenolol) was correctly identified by 11.1% of
      respondents. In warfarin -herb interactions section, the majority of respondents
      (66.7%) identified the interaction between green tea and warfarin. Approximately
      one-third of respondents (n=33) correctly classified warfarin interactions with
      cardamom. No significant difference was found between the health care
      professionals (p=0.49) for warfarin-drug interactions knowledge score and p= 0.52
      for warfarin- herb interactions knowledge score. CONCLUSION: This study suggests
      that health care professionals' knowledge of warfarin- drug-herb interactions was
      inadequate. Therefore, health care professionals should receive more education
      programs about drug-drug/herb interactions to provide appropriate patient
      counseling and optimal therapeutic outcomes.

PMID- 27022382
TI  - Pattern of physical activity among persons with type 2 diabetes with special
      consideration to daily routine.
AB  - OBJECTIVE: Physical activity is essential in maintaining a healthy lifestyle.
      Physical activity can improve general health, quality of life and diabetes
      management. The aim and objective of the study was to assess the physical
      activity trends in daily routine of people with type 2 diabetes. METHODS: Two
      hundred persons with diabetes from four different clinical settings were included
      to access the trends of physical activity using a customized questionnaire EPIC
      2. Pattern of physical activity was assessed across a set of domains including
      sleep time, hours of TV watch, preferred mode of transport for specific distance
      and household activities. Data was analyzed using SPSS 21. RESULTS: Out of 200
      persons with diabetes, 104(52%) were male and 96 (48%) were female. Out of the
      total sample of patients, 85 (81.7%) Male and 80 (83.3%) female patients
      preferred walk to cover a distance of less than one mile. There was a significant
      difference in selection of mode of transport for all other specified distance,
      esp. in female patients with both age groups. There was insignificant difference
      for physical activity pattern related to household activities in young and
      elderly male subjects. The mean sleeping time for younger male subjects on
      weekend was 464.31+/- 88.88 minutes/day and for elder it was 418.65+/- 102.66
      minutes/day while for young female subjects was 476.25+/- 113.74 minutes/day and
      in female elderly subjects it was 420.62+/- 120.62 minutes/day respectively.
      CONCLUSION: In type 2 diabetics we observed a low level of physical activity
      which may be detrimental for the control of diabetes mellitus.

PMID- 27022383
TI  - Comparing the Impact of Topical Application of Human Milk and Chlorhexidine on
      Cord Separation Time in Newborns.
AB  - OBJECTIVES: The best umbilical cord care after birth is a controversial issue.
      Aim of this research was to compare the effect of topical application of human
      milk and chlorhexidin on cord separation time in newborns. METHODS: One hundred
      seventy four neonates attending from hospitals affiliated to Kashan University of
      Medical Sciences were included. Newborns from birth were randomized to two
      groups. In group mother's milk, mother will rub her own milk to cord stump two
      times a day. chlorhexidin (group 2) were applied to the umbilical stump every 12
      hours. The time to umbilical cord separation and any discomfort such as
      infection, hemorrhage, and discharge and odor were documented. Data was analyzed
      by SPSS software. Independent Samples t-Test, chi(2), Fisher were used in this
      study. RESULTS: Results showed a significant statistical difference between cord
      separation time in two groups and the mean cord separation time in the human milk
      group (7.15+/-2.15days) was shorter than the chlorhexidin group (13.28+/-6.79
      days). In addition, a significant correlation was found between Signs of
      infection (discharge, redness, swelling and odor) in both groups. CONCLUSIONS:
      Topical application of breast milk on umbilical cord care leads to quick cord
      separation time and can be used as easy, cheep, non injury methods for umbilical
      cord care.

PMID- 27022384
TI  - The role of sigmoidoscopy in thediagnosis and treatment of sigmoid volvulus.
AB  - Sigmoid volvulus (SV) is a rare form of acute intestinal obstruction in which the
      sigmoid colon wraps around itself. The disease generally presents as a mechanical
      bowel obstruction with clinical features that are not pathognomonic. Similarly, X
      ray films are not diagnostic in most cases. It is difficult to establish the
      correct preoperative diagnosis when CT and MRI are not used. The principal
      strategy in the treatment of SV in uncomplicated patients is emergency endoscopic
      detorsion followed by elective surgery; emergent surgery is required in patients
      with bowel gangrene, bowel perforation, peritonitis, or unsuccessful endoscopic
      treatment. In this review, we have discussed the role of sigmoidoscopy in the
      diagnosis and treatment of SV. Additionally, we have retrospectively and
      prospectively evaluated our 49-year, 987-patient clinical experience, the largest
      single-center SV series ever reported. 

PMID- 27022385
TI  - Impact of different orthodontic treatment modalities on Airway: A literature
      review.
AB  - This review focused on airway dysfunctions and orthodontic treatment modalities.
      A systematic search of the dental literature was performed using PubMed and Web
      of Science library database. Different combinations of search terms related to
      airway and orthodontic treatment were used. Any Non-English articles were
      excluded. Among titles found, abstract and full articles were reviewed.
      References from all the relevant articles were hand-searched to include more
      articles. Forty articles which were found relevant were included in the review.
      Surgical, orthopedic and fixed appliance therapy has been advocated by clinicians
      to treat patients with airway dysfunctions. These treatment modalities differ
      from patient to patient and have to be considered based on lot of criterion. The
      reviewed studies were not convincing in providing information about the
      orthodontic treatment modalities; further research regarding the same could be
      encouraging. 

PMID- 27022386
TI  - Coffee Consumption and Pancreatic Cancer Risk: An Update Meta-analysis of Cohort
      Studies.
AB  - BACKGROUND & OBJECTIVE: The results of epidemiologic studies on the relationship
      between the coffee consumption and pancreatic cancer risk were inconsistent.
      Thus, we performed an update meta-analysis of cohort studies to quantitatively
      summarize the association between coffee consumption and pancreatic cancer risk.
      METHODS: We searched CBM (China Biology Medicine disc) and MEDLINE for studies of
      coffee consumption and pancreatic cancer risk up to June 2015. A total of 20
      cohort studies were identified in this meta-analysis, and we analyzed these
      studies using random effects model. The dose-response analysis was conducted too.
      RESULTS: The overall relative risk (RR) for highest coffee consumption versus
      lowest coffee consumption was 0.75 (95% Confidence Interval (CI), 0.63-0.86).
      Statistic significant heterogeneity was found among these studies (I (2) =37.8%,
      P for heterogeneity =0.045). The pooled RR for increment of 1 cup/day of coffee
      consumption was 0.99 (95%CI, 0.96-1.03) for the nine studies, without
      statistically significant. CONCLUSIONS: High coffee consumption is associated
      with a reduced pancreatic cancer risk. However, the result should be accepted
      with caution, due to the potential confounder and bias could not be excluded.
      Further well designed studies are needed to confirm the finding.

PMID- 27022387
TI  - Inflammatory myofibroblastic tumor: A rare cause of invagination in adults.
AB  - Inflammatory myofibroblastic tumor (IMT) is a distinct pseudosarcomatous lesion
      arising in the soft tissues and interior organs of children and young adults. It
      is rarely seen in adults. It was first described in lungs. IMT can occur in any
      location in the body. However, it is seen most commonly in lungs, intestinal
      mesentery and liver. Non-mesenteric alimentary tract IMT's are quite rare. The
      presented case is an ileal IMT that caused small bowel invagination. A 38 year
      old male patient presented to the emergency department with the complaint of
      diffuse abdominal pain, distension and no passage of gas or stools for two days.
      An abdominal examination revealed distension and tenderness in the abdomen with
      no guarding or rebound tenderness. Computerized tomography (CT) of the abdomen
      was ordered. CT revealed an image compatible with invagination of the right lower
      quadrant of the abdomen and a mass inside the lumen measuring 4x3x3cm. The mass
      causing invagination was detected during the surgical operation. A segmentary
      small bowel resection and ileoileal anastomosis was performed. The patient was
      discharged uneventfully on the postoperative sixth day. The diagnosis of IMT was
      confirmed histologically and immunochemically. 

PMID- 27022388
TI  - Bile duct stone formation around a Prolene suture after cholangioenterostomy.
AB  - The iatrogenic cause of bile duct stone formation is mainly due to suture
      materials, especially silk sutures. In recent years, Prolene and Vicryl sutures
      have been widely used in biliary surgery, and bile duct stone formation related
      to sutures are seemingly becoming rare, as there has only been one report of bile
      duct stone formation caused by Prolene sutures in the literature. In the last few
      years we have had two cases of Prolene suture-related bile duct stone formation
      within our unit. We therefore suggest that Vicryl sutures should be used as the
      first choice in biliary surgery, in order to prevent the formation of iatrogenic
      bile duct stones. 

PMID- 27022389
TI  - Differential Roles of Peroxisome Proliferator-Activated Receptor-alpha and
      Receptor-gamma on Renal Crystal Formation in Hyperoxaluric Rodents.
AB  - Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and
      oxidative molecule expression were investigated in a hyperoxaluric rodent model
      to evaluate the in vivo efficacy of PPAR agonists in preventing renal crystal
      formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone
      model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects
      of the PPARalpha agonist fenofibrate and PPARgamma agonist pioglitazone were also
      assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria. Crystal
      formation, inflammation, cell injury, apoptosis, and oxidative stress were
      compared to those of vehicle-treated controls. Quantitative reverse transcription
      polymerase chain reaction revealed that PPARalpha and PPARgamma expression
      decrease and increase, respectively, during crystal formation in hyperoxaluric
      kidneys. In addition, PPARalpha localized to the cytoplasm of both proximal and
      distal tubular cells, whereas PPARgamma accumulated in the nucleus of proximal
      tubular cells. Furthermore, renal crystal formation was significantly less
      prevalent in pioglitazone-treated rats but higher in the fenofibrate-treated and
      fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating
      that pioglitazone, but not fenofibrate, markedly decreased cell inflammation,
      oxidative stress, and apoptosis. Collectively, the results demonstrated that
      PPARgamma suppressed renal crystal formation via its antioxidative and anti
      inflammatory effects; however, the renotoxicity of PPARalpha may elicit the
      opposite effect. 

PMID- 27022390
TI  - Polyglycolic Acid Felt Sealing Method for Prevention of Bleeding Related to
      Endoscopic Submucosal Dissection in Patients Taking Antithrombotic Agents.
AB  - Background and Study Aims. When performing endoscopic submucosal dissection (ESD)
      for patients on antithrombotic agents, the frequency of delayed bleeding is
      expected to increase. The endoscopic polyglycolic acid (PGA) felt and fibrin glue
      sealing method could be a new method for prevention of delayed bleeding. Patients
      and Methods. The safety and efficacy of the endoscopic tissue sealing method with
      PGA sheets and fibrin glue for the prevention of post-ESD bleeding were examined
      in 104 patients taking antithrombotic agents. During the study period, 70
      patients taking antithrombotic agents did not undergo the sealing method, 36
      patients discontinued antithrombotic agents, and 724 patients had not received
      antithrombotic therapy. Results. Delayed bleeding rates were 3.8% (4/104) in the
      sealing group, 12.9% (9/70) in the nonsealing group, 8.3% (3/36) in the
      discontinuation group, and 4.6% (33/724) in the nonantithrombotic therapy group.
      Thus, the delayed bleeding rate was significantly lower in the sealing group than
      in the nonsealing group and comparable to that in the nonantithrombotic therapy
      group. Conclusions. This PGA felt and fibrin glue sealing method might become a
      promising post-ESD bleeding prevention method in patients taking antithrombotic
      agents (UMIN000013990, UMIN000013993). 

PMID- 27022391
TI  - A Comparison of a Fully Covered and an Uncovered Segmented Biodegradable
      Esophageal Stent in a Porcine Model: Preclinical Evaluation of Degradation,
      Complications, and Tissue Reactions.
AB  - Aims. This study was to compare the degradation, complications, and tissue
      reactions of two segmented biodegradable esophageal stents in a porcine model.
      Methods. Uncovered biodegradable segmented stents and fully covered biodegradable
      segmented stents (FCBDS) were transplanted into the porcine esophagus lumen. Data
      on biodegradation, complications, and tissue reactions were collected and
      compared. Results. All animals kept good general conditions. No severe
      complications and stents migration occurred. Stents degradation commenced at week
      3. Compared with uncovered stents, stents structure breakage and complete stents
      absorption in FCBDS were postponed for 1-2 weeks. Hyperplasia was prominent at
      early stage and ameliorated at late stage after stents insertion. Tissue
      reactions in FCBDS were milder than those in uncovered stents in the early stage.
      A longer degradation period was present in FCBDS than in uncovered stents, while
      FCBDS induced tissue reaction at late stage was mild. Conclusions. Biodegradable
      esophageal stents with a segmented trunk may be further evaluated in refractory
      benign esophagus strictures. This FCBDS may be advantageous compared with
      uncovered stents for a longer degradation period. 

PMID- 27022392
TI  - Cytotoxic Activity of Holothuria leucospilota Extract against Leishmania infantum
      In Vitro.
AB  - Leishmaniasis is a tropical parasitic infection. The resistance and toxicity
      issues are the major complications and remain significant consequences related to
      the treatment of leishmaniasis with the recent and classical drugs. Thus there is
      an immediate requirement to develop new compounds for the treatment of this
      protozoan disease. Sea cucumbers or holothurians are potentially presented as the
      marine sources of antimicrobial and cytotoxic compounds. The aim of this study
      was investigation of in vitro antileishmanial activity of methanol extract of
      body wall, coelomic fluid, and cuvierian organs of Holothuria leucospilota
      obtained from coastal parts of Persian Gulf against Leishmania infantum
      promastigotes and axenic amastigotes. The colorimetric MTT assay was used to
      determine L. infantum promastigotes and axenic amastigotes viability at different
      concentrations of the extracts and drug control (Glucantime(r)) at time dependent
      manner and the results are represented as IC50 (50% of inhibitory concentration).
      Coelomic fluid was the most active extract among the three different extracts of
      H. leucospilota against L. infantum promastigotes and axenic amastigotes with
      IC50s of 62.33 MUg/mL and 22.4 MUg/mL and 73 MUg/mL and 46 MUg/mL at 48 and 72
      hours after treatment, respectively. Cuvierian organs extract showed less
      toxicity with IC50s more than 1000 MUg/mL for both Leishmania infantum axenic
      amastigotes and promastigotes forms after 48 and 72 hours of exposure. Results
      acquired from the present study propose that the sea cucumber H. leucospilota may
      be a provoking source of antileishmanial compounds and could be a lead source in
      the development of the potent antileishmanial and cytotoxic drugs. 

PMID- 27022393
TI  - Hypothesis That Urethral Bulb (Corpus Spongiosum) Plays an Active Role in Male
      Urinary Continence.
AB  - The proximal urethral bulb in men is enlarged, surrounds the bulbous urethra, and
      extends dorsally towards the perineum. During intercourse engorgement takes place
      due to increased blood flow through the corpus spongiosum. Antegrade ejaculation
      is facilitated by contraction of the bulbospongiosus muscles during climax.
      Micturition during sexual stimulation is functionally inhibited. Supporting the
      bulb may indirectly facilitate continence in a certain subset of patients with
      postprostatectomy incontinence. During physical activity with increased abdominal
      pressure, reflex contraction of the pelvic floor muscles as well as the
      bulbospongiosus muscles occurs to support sphincter function and limit urinary
      incontinence. Operations to the prostate may weaken urinary sphincter function.
      It is hypothesized that the distal urinary sphincter may be supported indirectly
      by placing a hammock underneath the urethral bulb. During moments of physical
      stress the "cushion" of blood within the supported corpus spongiosum helps to
      increase the zone of coaptation within the sphincteric (membranous) urethra. This
      may lead to urinary continence in patients treated by a transobturator
      repositioning sling in patients with postprostatectomy incontinence. This paper
      describes the possible role of the urethral bulb in male urinary continence,
      including its function after retroluminal sling placement (AdVance, AdVance XP(r)
      Male Sling System, Minnetonka, USA). 

PMID- 27022394
TI  - Self-Optimized Biological Channels in Facilitating the Transmembrane Movement of
      Charged Molecules.
AB  - We consider an anisotropically two-dimensional diffusion of a charged molecule
      (particle) through a large biological channel under an external voltage. The
      channel is modeled as a cylinder of three structure parameters: radius, length,
      and surface density of negative charges located at the channel interior-lining.
      These charges induce inside the channel a potential that plays a key role in
      controlling the particle current through the channel. It was shown that to
      facilitate the transmembrane particle movement the channel should be reasonably
      self-optimized so that its potential coincides with the resonant one, resulting
      in a large particle current across the channel. Observed facilitation appears to
      be an intrinsic property of biological channels, regardless of the external
      voltage or the particle concentration gradient. This facilitation is very
      selective in the sense that a channel of definite structure parameters can
      facilitate the transmembrane movement of only particles of proper valence at
      corresponding temperatures. Calculations also show that the modeled channel is
      nonohmic with the ion conductance which exhibits a resonance at the same channel
      potential as that identified in the current. 

PMID- 27022395
TI  - Thyroid-Specific Genes Expression Uncovered Age-Related Differences in Pediatric
      Thyroid Carcinomas.
AB  - Despite a more advanced stage of disease at presentation, a better response to
      radioiodine (RAI) therapy and a reduced overall mortality have been reported in
      pediatric differentiated thyroid cancer (DTC) in comparison to adult DTC. Few
      studies suggested that the better response to RAI therapy in pediatric patients
      might be associated with an increased expression of NIS. However, a marked
      heterogeneity within the pediatric group has been recognized. Children (<10 years
      old) usually present a more aggressive disease than adolescents (>=10-18 years
      old). By analyzing the expression of thyroid-specific genes in 38 sporadic
      pediatric tumors, we show that the expression of NIS, PDS, and TSHR was lower in
      children than adolescents (P < 0.05). A linear regression confirmed the
      association between NIS expression and age. Most significantly, NIS was expressed
      at similar levels in DTC from children and adults, whereas PDS and TSHR
      expression was even lower in DTC from children, compared to adolescents and
      adults. Our data suggest that biological behaviors of DTC in adolescents might
      differ from those in children and adults. Therefore, the premise that the
      expression of thyroid-specific genes is higher in tumors from pediatric patients
      than in adults is not entirely true and might be too oversimplified. 

PMID- 27022396
TI  - Higher Serum Uric Acid Is Associated with Higher Bone Mineral Density in Chinese
      Men with Type 2 Diabetes Mellitus.
AB  - Accumulating evidence suggests that oxidative stress is associated with
      osteoporosis. Serum uric acid (UA) is a strong endogenous antioxidant. Therefore,
      we investigated the relationship between the serum UA and BMD in Chinese men with
      T2DM. In this cross-sectional study of 621 men with T2DM, BMDs at lumbar spine
      (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray
      absorptiometry (DXA). Serum levels of UA, calcium (Ca), 25-OH vitamin D3 (vitD3),
      parathyroid hormone (PTH), and creatinine (Cr) were also tested. Data analyses
      revealed that serum UA levels were positively associated with BMD at all sites (p
      < 0.05) in men with T2DM after adjusting for multiple confounders. The serum UA
      levels were positively correlated with body weight (r = 0.322), body mass index
      (BMI) (r = 0.331), Ca (r = 0.179), and Cr (r = 0.239) (p < 0.001) and were also
      positively associated with the concentrations of PTH (r = 0.10, p < 0.05). When
      compared with those in the lowest tertile of UA levels, men with T2DM in the
      highest tertile had a lower prevalence of osteoporosis or osteopenia (adjusted
      odds ratio 0.54, 95% confidence interval [CI] 0.31-0.95). These data suggest that
      higher serum levels of UA are associated with higher BMDs and lower risks of
      osteoporosis in Chinese men with T2DM. 

PMID- 27022397
TI  - Multiple Reaction Monitoring Mode Based Liquid Chromatography-Mass Spectrometry
      Method for Simultaneous Quantification of Brassinolide and Other Plant Hormones
      Involved in Abiotic Stresses.
AB  - Plant hormones are the key regulators of adaptive stress response. Abiotic
      stresses such as drought and salt are known to affect the growth and productivity
      of plants. It is well known that the levels of plant hormones such as zeatin
      (ZA), abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), and
      brassinolide (BR) fluctuate upon abiotic stress exposure. At present, there is
      not any single suitable liquid chromatography-mass spectrometry (LC-MS) method
      for simultaneous analysis of BR and other plant hormones involved in abiotic
      stresses. In the present study, we developed a simple, sensitive, and rapid
      method for simultaneous analysis of five major plant hormones, ZA, ABA, JA, SA,
      and BR, which are directly or indirectly involved in drought and salt stresses.
      The optimized extraction procedure was simple and easy to use for simultaneous
      measurement of these plant hormones in Arabidopsis thaliana. The developed method
      is highly reproducible and can be adapted for simultaneous measurement of changes
      in plant hormones (ZA, ABA, JA, SA, and BR) in response to abiotic stresses in
      plants like A. thaliana and tomato. 

PMID- 27022398
TI  - Production of Palmitoleic and Linoleic Acid in Oleaginous and Nonoleaginous Yeast
      Biomass.
AB  - We investigated the possibility of utilizing both oleaginous yeast species
      accumulating large amounts of lipids (Yarrowia lipolytica, Rhodotorula glutinis,
      Trichosporon cutaneum, and Candida sp.) and traditional biotechnological
      nonoleaginous ones (Kluyveromyces polysporus, Torulaspora delbrueckii, and
      Saccharomyces cerevisiae) as potential producers of dietetically important major
      fatty acids. The main objective was to examine the cultivation conditions that
      would induce a high ratio of dietary fatty acids and biomass. Though genus
      dependent, the type of nitrogen source had a higher influence on biomass yield
      than the C/N ratio. The nitrogen source leading to the highest lipid accumulation
      was potassium nitrate, followed by ammonium sulfate, which is an ideal nitrogen
      source supporting, in both oleaginous and nonoleaginous species, sufficient
      biomass growth with concomitantly increased lipid accumulation. All yeast strains
      displayed high (70-90%) content of unsaturated fatty acids in total cell lipids.
      The content of dietary fatty acids of interest, namely, palmitoleic acid and
      linoleic acid, reached in Kluyveromyces and Trichosporon strains over 50% of
      total fatty acids and the highest yield, over 280 mg per g of dry cell weight of
      these fatty acids, was observed in Trichosporon with ammonium sulfate as nitrogen
      source at C/N ratio 70. 

PMID- 27022399
TI  - Clumping and Viability of Bone Marrow Derived Mesenchymal Stromal Cells under
      Different Preparation Procedures: A Flow Cytometry-Based In Vitro Study.
AB  - Complications of microocclusions have been reported after intra-arterial delivery
      of mesenchymal stromal cells. Hence, quantification and efficient limitation of
      cell clumps in suspension before transplantation is important to reduce the risk.
      We used a flow cytometry-based pulse-width assay to assess the effects of
      different cell suspension concentrations (0.2-2.0 * 10(6)/mL), storage solutions
      (complete growth medium, Dulbecco's phosphate-buffered saline, and normal
      saline), storage time in suspension (0-9 h), and freeze-thawing procedure on the
      clumping of rat bone marrow derived mesenchymal stromal cells (BMMSCs) and also
      evaluated cell viability at the same time. Surprisingly, increasing the cell
      concentration did not result in more cell clumps in vitro. Freshly harvested
      (fresh) cells in normal saline had significantly fewer cell clumps and also
      displayed high viability (>90%). A time-dependent reduction in viability was
      observed for cells in all three storage solutions, without any significant change
      in the clumping tendency except for cells in medium. Fresh cells were more viable
      than their frozen-thawed counterparts, and fresh cells in normal saline had fewer
      cell clumps. In conclusion, cell clumping and viability could be affected by
      different cell preparation procedures, and quantification of cell clumping can be
      conducted using the flow cytometry-based pulse-width assay before intra-arterial
      cell delivery. 

PMID- 27022400
TI  - 3D Spheroid Culture Enhances the Expression of Antifibrotic Factors in Human
      Adipose-Derived MSCs and Improves Their Therapeutic Effects on Hepatic Fibrosis.
AB  - Three-dimensional (3D) cell culture has been reported to increase the therapeutic
      potentials of mesenchymal stem cells (MSCs). However, the action mechanisms of 3D
      MSCs vary greatly and are far from being thoroughly investigated. In this study,
      we aimed to investigate the therapeutic effects of 3D spheroids of human adipose
      derived MSCs for hepatic fibrosis. Our results showed that 3D culture enhanced
      the expression of antifibrotic factors by MSCs, including insulin growth factor 1
      (IGF-1), interleukin-6 (IL-6), and hepatocyte growth factor (HGF). In vitro
      studies indicated conditioned medium of 3D cultured MSCs protected hepatocytes
      from cell injury and apoptosis more effectively compared with 2D cultured cells.
      More importantly, when transplanted into model mice with hepatic fibrosis, 3D
      spheroids of MSCs were more beneficial in ameliorating hepatic fibrosis and
      improving liver function than 2D cultured cells. Therefore, the 3D culture
      strategy improved the therapeutic effects of MSCs and might be promising for
      treatment of hepatic fibrosis. 

PMID- 27022401
TI  - Polydatin Protects Bone Marrow Stem Cells against Oxidative Injury: Involvement
      of Nrf 2/ARE Pathways.
AB  - Polydatin, a glucoside of resveratrol, has been reported to possess potent
      antioxidative effects. In the present study, we aimed to investigate the effects
      of polydatin in bone marrow-derived mesenchymal stem cells (BMSCs) death caused
      by hydrogen peroxide (H2O2), imitating the microenvironment surrounding
      transplanted cells in the injured spinal cord in vitro. In our study, MTT results
      showed that polydatin effectively prevented the decrease of cell viability caused
      by H2O2. Hochest 33258, Annexin V-PI, and Western blot assay showed H2O2-induced
      apoptosis in BMSCs, which was attenuated by polydatin. Further studies indicated
      that polydatin significantly protects BMSCs against apoptosis due to its
      antioxidative effects and the regulation of Nrf 2/ARE pathway. Taken together,
      our results indicate that polydatin could be used in combination with BMSCs for
      the treatment of spinal cord injury by improving the cell survival and oxidative
      stress microenvironments. 

PMID- 27022402
TI  - Components and Anti-HepG2 Activity Comparison of Lycopodium Alkaloids from Four
      Geographic Origins.
AB  - Lycopodium japonicum Thunb. has attracted great interests due to its rich
      alkaloids with significant anticancer activity. However, significant chemical
      differences often exist in a plant species from different geographic origins and
      affect its quality and bioactivities. Thus, it is urgent to reveal their chemical
      and biological distinctions at the molecular level. In this context, a
      comparative chemical analysis of LAs using HPLC-UV-ESI-MS/MS was firstly
      conducted and resulted in the detection of 46 LAs, 28 of which were identified,
      and a series of unique LAs markers, such as peaks 2, 9, 10, and 11, were further
      found to be characteristic LAs and selected as markers from four different
      origins for their quality control. In parallel, the comparative bioactivity assay
      revealed that the total LAs from Hubei province exhibited much higher inhibitory
      rate at 65.95% against HepG2 cells than those at 26.72%, 20.26%, and 33.62% for
      Kenya, Guangxi province, and Zhejiang province in China, respectively. To this
      end, significant chemical fingerprinting differences and discrepancies in
      bioactivity of LAs were explored firstly, which could provide valuable
      information for quality control and further activity studies on LAs from
      different sources and promote their better pharmaceutical applications in the
      future as well. 

PMID- 27022403
TI  - The Role of Nigella sativa and Its Active Constituents in Learning and Memory.
AB  - The loss of the ability for learning and memory is a prominent feature of
      dementia, which affects millions of individuals all over the world, due to either
      neurodegenerative diseases or brain injury. Although a lot of information is
      known about the pathology involved, treatment remains elusive at best. The Black
      Seed of Nigella sativa has been historically and religiously used for thousands
      of years for preventing and treating many different kinds of diseases. This
      review article looks at Nigella sativa and its potential role in facilitating
      learning and memory. The possible use of this seed's extract or compounds
      isolated from it, such as thymoquinone, for treating damaged brain neural tissue
      is discussed. The evidence presented in this paper appears to be supporting the
      hypothesis that this plant and/or its bioactive constituents can enhance learning
      and memory in health and disease in animals and humans. 

PMID- 27022404
TI  - An Extract of Chinpi, the Dried Peel of the Citrus Fruit Unshiu, Enhances Axonal
      Remyelination via Promoting the Proliferation of Oligodendrocyte Progenitor
      Cells.
AB  - The aging-induced decrease in axonal myelination/remyelination is due to impaired
      recruitment and differentiation of oligodendrocyte progenitor cells (OPCs). Our
      previous studies have shown that a monoclonal antibody to DEAD (Asp-Glu-Ala-Asp)
      box polypeptide 54 (Ddx54), a member of the DEAD box family of RNA helicases, (1)
      specifically labels oligodendrocyte lineages, (2) binds to mRNA and protein
      isoforms of myelin basic proteins (MBP), and (3) regulates migration of OPCs from
      ventricular zone to corpus callosum in mice. It has also been demonstrated that
      specific loss of a 21.5 kDa MBP isoform (MBP21.5) reflects demyelination status,
      and oral administration of an extract of Chinpi, citrus unshiu peel, reversed the
      aging-induced demyelination. Here, we report that Chinpi treatment induced a
      specific increase in the MBP21.5, led to the reappearance of Ddx54-expressing
      cells in ventricular-subventricular zone and corpus callosum of aged mice, and
      promoted remyelination. Treatment of in vitro OPC cultures with Chinpi
      constituents, hesperidin plus narirutin, led to an increase in 5-bromo-2'
      deoxyuridine incorporation in Ddx54-expressing OPCs, but not in NG2- or Olig2
      expressing cell populations. The present study suggests that Ddx54 plays crucial
      role in remyelination. Furthermore, Chinpi and Chinpi-containing herbal medicines
      may be a therapeutic option for the aging-induced demyelination diseases. 

PMID- 27022405
TI  - Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with
      Ordinary Differential Equations.
AB  - Despite improvements in cancer therapy and treatments, tumor recurrence is a
      common event in cancer patients. One explanation of recurrence is that cancer
      therapy focuses on treatment of tumor cells and does not eradicate cancer stem
      cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that
      their role is to maintain homeostasis. That is, when the population of tumor
      cells is reduced or depleted by treatment, CSCs will repopulate the tumor,
      causing recurrence. In this paper, we study the application of the CSC Hypothesis
      to the treatment of glioblastoma multiforme by immunotherapy. We extend the work
      of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence
      of a recurrence state, and provide an analysis of possible cancerous states and
      their dependence on treatment levels. 

PMID- 27022406
TI  - Predicting Renal Failure Progression in Chronic Kidney Disease Using Integrated
      Intelligent Fuzzy Expert System.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a covert disease. Accurate prediction
      of CKD progression over time is necessary for reducing its costs and mortality
      rates. The present study proposes an adaptive neurofuzzy inference system (ANFIS)
      for predicting the renal failure timeframe of CKD based on real clinical data.
      METHODS: This study used 10-year clinical records of newly diagnosed CKD
      patients. The threshold value of 15 cc/kg/min/1.73 m(2) of glomerular filtration
      rate (GFR) was used as the marker of renal failure. A Takagi-Sugeno type ANFIS
      model was used to predict GFR values. Variables of age, sex, weight, underlying
      diseases, diastolic blood pressure, creatinine, calcium, phosphorus, uric acid,
      and GFR were initially selected for the predicting model. RESULTS: Weight,
      diastolic blood pressure, diabetes mellitus as underlying disease, and current
      GFR(t) showed significant correlation with GFRs and were selected as the inputs
      of model. The comparisons of the predicted values with the real data showed that
      the ANFIS model could accurately estimate GFR variations in all sequential
      periods (Normalized Mean Absolute Error lower than 5%). CONCLUSIONS: Despite the
      high uncertainties of human body and dynamic nature of CKD progression, our model
      can accurately predict the GFR variations at long future periods.

PMID- 27022407
TI  - The Research of Feature Extraction Method of Liver Pathological Image Based on
      Multispatial Mapping and Statistical Properties.
AB  - We propose a new feature extraction method of liver pathological image based on
      multispatial mapping and statistical properties. For liver pathological images of
      Hematein Eosin staining, the image of R and B channels can reflect the
      sensitivity of liver pathological images better, while the entropy space and
      Local Binary Pattern (LBP) space can reflect the texture features of the image
      better. To obtain the more comprehensive information, we map liver pathological
      images to the entropy space, LBP space, R space, and B space. The traditional
      Higher Order Local Autocorrelation Coefficients (HLAC) cannot reflect the overall
      information of the image, so we propose an average correction HLAC feature. We
      calculate the statistical properties and the average gray value of pathological
      images and then update the current pixel value as the absolute value of the
      difference between the current pixel gray value and the average gray value, which
      can be more sensitive to the gray value changes of pathological images. Lastly
      the HLAC template is used to calculate the features of the updated image. The
      experiment results show that the improved features of the multispatial mapping
      have the better classification performance for the liver cancer. 

PMID- 27022408
TI  - A generic schema and data collection forms applicable to diverse entomological
      studies of mosquitoes.
AB  - BACKGROUND: Standardized schemas, databases, and public data repositories are
      needed for the studies of malaria vectors that encompass a remarkably diverse
      array of designs and rapidly generate large data volumes, often in resource
      limited tropical settings lacking specialized software or informatics support.
      RESULTS: Data from the majority of mosquito studies conformed to a generic
      schema, with data collection forms recording the experimental design, sorting of
      collections, details of sample pooling or subdivision, and additional
      observations. Generically applicable forms with standardized attribute
      definitions enabled rigorous, consistent data and sample management with generic
      software and minimal expertise. Forms use now includes 20 experiments, 8
      projects, and 15 users at 3 research and control institutes in 3 African
      countries, resulting in 11 peer-reviewed publications. CONCLUSION: We have
      designed generic data schema that can be used to develop paper or electronic
      based data collection forms depending on the availability of resources. We have
      developed paper-based data collection forms that can be used to collect data from
      majority of entomological studies across multiple study areas using standardized
      data formats. Data recorded on these forms with standardized formats can be
      entered and linked with any relational database software. These informatics tools
      are recommended because they ensure that medical entomologists save time, improve
      data quality, and data collected and shared across multiple studies is in
      standardized formats hence increasing research outputs.

PMID- 27022409
TI  - Overview: referrals for genetic evaluation from child psychiatrists.
AB  - A growing multitude of known genetic diagnoses can result in presentation to
      child psychiatry. For numerous reasons, it is important to identify a genetic
      etiology in child psychiatry patients when it is present. Genetic diagnoses can
      guide treatment and enable access to specialized clinics and appropriate
      screening measures. They can also allow for genetic counseling for the patient
      and family. A better understanding of etiology with a named diagnosis can itself
      be of great value to many patients and families; prognostic information can be
      empowering. Since patients with genetic conditions may present to psychiatric
      care in diverse ways, child psychiatrists must decide who to refer for genetic
      evaluation. Here we create a table to provide a framework of concerning/notable
      history and exam features that a practicing child psychiatrist may encounter that
      should prompt one to consider whether a larger, unifying genetic diagnosis is at
      hand. We hope this framework will facilitate referral of child psychiatry
      patients to genetics so that more patients can benefit from an appropriate
      diagnosis. 

PMID- 27022410
TI  - Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic
      Activity of Cell-Derived Microparticles.
AB  - Cell-derived microparticles (MPs) are nano-sized vesicles released by activated
      cells in the extracellular milieu. They act as vectors of biological activity by
      carrying membrane-anchored and cytoplasmic constituents of the parental cells.
      Although detection and characterization of cell-derived MPs may be of high
      diagnostic and prognostic values in a number of human diseases, reliable
      measurement of their size, number and biological activity still remains
      challenging using currently available methods. In the present study, we developed
      a protocol to directly image and functionally characterize MPs using high
      resolution laser-scanning confocal microscopy. Once trapped on annexin-V coated
      micro-wells, we developed several assays using fluorescent reporters to measure
      their size, detect membrane antigens and evaluate proteolytic activity (nano
      zymography). In particular, we demonstrated the applicability and specificity of
      this method to detect antigens and proteolytic activities of tissue-type
      plasminogen activator (tPA), urokinase and plasmin at the surface of engineered
      MPs from transfected cell-lines. Furthermore, we were able to identify a subset
      of tPA-bearing fibrinolytic MPs using plasma samples from a cohort of ischemic
      stroke patients who received thrombolytic therapy and in an experimental model of
      thrombin-induced ischemic stroke in mice. Overall, this method is promising for
      functional characterization of cell-derived MPs. 

PMID- 27022411
TI  - Enhanced Anti-Tumor Efficacy through a Combination of Integrin alphavbeta6
      Targeted Photodynamic Therapy and Immune Checkpoint Inhibition.
AB  - "Training" the host immune system to recognize and systemically eliminate
      residual tumor lesions and micrometastases is a promising strategy for cancer
      therapy. In this study, we investigated whether integrin alphavbeta6-targeted
      photodynamic therapy (PDT) of tumors using a phthalocyanine dye-labeled probe
      (termed DSAB-HK) could trigger the host immune response, and whether PDT in
      combination with anti-PD-1 immune checkpoint inhibition could be used for the
      effective therapy of primary tumors and metastases. By near-infrared fluorescence
      imaging, DSAB-HK was demonstrated to specifically target either subcutaneous
      tumors in a 4T1 mouse breast cancer model or firefly luciferase stably
      transfected 4T1 (4T1-fLuc) lung metastatic tumors. Upon light irradiation, PDT by
      DSAB-HK significantly inhibited the growth of subcutaneous 4T1 tumors, and in
      addition promoted the maturation of dendritic cells and their production of
      cytokines, which subsequently stimulated the tumor recruitment of CD8(+)
      cytotoxic T lymphocytes. Furthermore, DSAB-HK PDT of the first tumor followed by
      PD-1 blockade markedly suppressed the growth of a second subcutaneous tumor, and
      also slowed the growth of 4T1-fLuc lung metastasis as demonstrated by serial
      bioluminescence imaging. Together, our results demonstrated the synergistic
      effect of tumor-targeted PDT and immune checkpoint inhibition for improving anti
      tumor immunity and suppressing tumor growth/metastasis. 

PMID- 27022412
TI  - Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese
      Patients with Wilson's Disease Guides Genetic Diagnosis.
AB  - BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder of copper
      metabolism caused by ATP7B pathogenic mutations. The symptoms of WD can be
      effectively prevented if the affected individuals are identified and intervened
      early. However, clinical utility of this molecular analysis is challenging due to
      hundreds of variants with various clinical effects in the gene. Here, we aim to
      describe the spectrum of ATP7B variants and assess their clinical effects in the
      Han Chinese population. METHODS: The ATP7B gene was directly sequenced in 632
      unrelated WD patients and 503 unrelated healthy individuals. The effects of
      identified variants were classified according to the American College of Medical
      Genetics and Genomics (ACMG) standards and guidelines. Different frequency of
      variants observed in both cases and controls were tested using Chi-square or
      Fisher's exact tests. RESULTS: We detected 161 non-synonymous variants in these
      632 WD patients, 58 of which were novel. Among these variants, 78, 64, 8, 4, and
      7 were classified as 'pathogenic variants', 'likely pathogenic variants',
      'variants with uncertain significance', 'likely benign variants', and 'benign
      variants', respectively. Ninety percent (569/632) of these WD patients can be
      genetically diagnosed with two or more 'pathogenic' or 'likely pathogenic'
      variants. The 14 most common disease-causing variants were found at least once in
      94% (537/569) of genetically diagnosed patients. CONCLUSIONS: These data expand
      the spectrum of ATP7B variants and facilitate effective screening for ATP7B
      variants for early diagnosis of WD and development of individualized treatment
      regimens.

PMID- 27022413
TI  - Multimodal Somatostatin Receptor Theranostics Using [(64)Cu]Cu-/[(177)Lu]Lu-DOTA
      (Tyr(3))octreotate and AN-238 in a Mouse Pheochromocytoma Model.
AB  - Pheochromocytomas and extra-adrenal paragangliomas (PHEO/PGLs) are rare
      catecholamine-producing chromaffin cell tumors. For metastatic disease, no
      effective therapy is available. Overexpression of somatostatin type 2 receptors
      (SSTR2) in PHEO/PGLs promotes interest in applying therapies using somatostatin
      analogs linked to radionuclides and/or cytotoxic compounds, such as [(177)Lu]Lu
      DOTA-(Tyr(3))octreotate (DOTATATE) and AN-238. Systematic evaluation of such
      therapies for the treatment of PHEO/PGLs requires sophisticated animal models. In
      this study, the mouse pheochromocytoma (MPC)-mCherry allograft model showed high
      tumor densities of murine SSTR2 (mSSTR2) and high tumor uptake of [(64)Cu]Cu
      DOTATATE. Using tumor sections, we assessed mSSTR2-specific binding of DOTATATE,
      AN-238, and somatostatin-14. Therapeutic studies showed substantial reduction of
      tumor growth and tumor-related renal monoamine excretion in tumor-bearing mice
      after treatment with [(177)Lu]Lu-DOTATATE compared to AN-238 and doxorubicin.
      Analyses did not show agonist-dependent receptor downregulation after single
      mSSTR2-targeting therapies. This study demonstrates that the MPC-mCherry model is
      a uniquely powerful tool for the preclinical evaluation of SSTR2-targeting
      theranostic applications in vivo. Our findings highlight the therapeutic
      potential of somatostatin analogs, especially of [(177)Lu]Lu-DOTATATE, for the
      treatment of metastatic PHEO/PGLs. Repeated treatment cycles, fractionated
      combinations of SSTR2-targeting radionuclide and cytotoxic therapies, and other
      adjuvant compounds addressing additional mechanisms may further enhance
      therapeutic outcome. 

PMID- 27022414
TI  - A Comparison Study of iTEP Nanoparticle-Based CTL Vaccine Carriers Revealed a
      Surprise Relationship between the Stability and Efficiency of the Carriers.
AB  - Vaccine carriers have been shown to enhance cytotoxic T lymphocyte (CTL) epitope
      peptide vaccines by addressing intrinsic limitations of the vaccines. We have
      previously developed an immune-tolerant elastin-like polypeptide (iTEP)-based
      nanoparticle (NP) as an effective and unique CTL vaccine carrier. The NP is
      unique for its humoral immune tolerance, flexible structure, and ability to
      deliver CTL vaccines as polypeptide fusions. Here, we aimed to improve the NP by
      increasing its stability since we found it was not stable. We thus generated a
      more stable iTEP NP (ST-NP) and used it to deliver a CTL peptide vaccine,
      SIINFEKL. However, we surprisingly found that the ST-NP had a lower efficiency
      than the previously developed, marginally stable iTEP NP (MS-NP) in terms of
      promoting vaccine presentation and vaccine-induced CTL responses. On the other
      hand, dendritic cells (DCs) showed preferential uptake of the ST-NP but not the
      MS-NP. To develop an iTEP vaccine carrier that outperforms both the MS-NP and the
      ST-NP, we devised an iTEP NP that has a changeable stability responsive to a
      cytosolic, reductive environment, termed reductive environment-dependent NP or
      RED-NP. The RED-NP showed an intermediate ability to promote vaccine presentation
      and T cell responses in vitro between the MS-NP and the ST-NP. However, the RED
      NP induced the strongest CTL responses in vivo among all three NPs. In
      conclusion, iTEP NPs that have a dynamically changeable stability are most
      effective to deliver and enhance CTL peptide vaccines. The work also demonstrated
      the versatile nature of iTEP vaccine carriers. 

PMID- 27022415
TI  - Cisplatin Prodrug-Conjugated Gold Nanocluster for Fluorescence Imaging and
      Targeted Therapy of the Breast Cancer.
AB  - Theranostic nanomedicine has emerged as a promising modality for cancer diagnosis
      and treatment. In this study, we report the fabrication of fluorescence gold
      nanoclusters (GNC) conjugated with a cisplatin prodrug and folic acid (FA) (FA
      GNC-Pt) for fluorescence imaging and targeted chemotherapy of breast cancer. The
      physio-chemical properties of FA-GNC-Pt nanoparticles are thoroughly
      characterized by fluorescence/UV-Vis spectroscopic measurement, particle size and
      zeta-potential examination. We find that FA-modification significantly
      accelerated the cellular uptake and increased the cytotoxicity of GNC-Pt
      nanoparticles in murine 4T1 breast cancer cells. Fluorescence imaging in vivo
      using 4T1 tumor bearing nude mouse model shows that FA-GNC-Pt nanoparticles
      selectively accumulate in the orthotopic 4T1 tumor and generate strong
      fluorescence signal due to the tumor targeting effect of FA. Moreover, we
      demonstrate that FA-GNC-Pt nanoparticles significantly inhibit the growth and
      lung metastasis of the orthotopically implanted 4T1 breast tumors. All these data
      imply a good potential of the GNC-based theranostic nanoplatform for fluorescence
      tumor imaging and cancer therapy. 

PMID- 27022416
TI  - A Phosphorus Phthalocyanine Formulation with Intense Absorbance at 1000 nm for
      Deep Optical Imaging.
AB  - Although photoacoustic computed tomography (PACT) operates with high spatial
      resolution in biological tissues deeper than other optical modalities, light
      scattering is a limiting factor. The use of longer near infrared wavelengths
      reduces scattering. Recently, the rational design of a stable phosphorus
      phthalocyanine (P-Pc) with a long wavelength absorption band beyond 1000 nm has
      been reported. Here, we show that when dissolved in liquid surfactants, P-Pc can
      give rise to formulations with absorbance of greater than 1000 (calculated for a
      1 cm path length) at wavelengths beyond 1000 nm. Using the broadly accessible
      Nd:YAG pulse laser emission output of 1064 nm, P-Pc could be imaged through 11.6
      cm of chicken breast with PACT. P-Pc accumulated passively in tumors following
      intravenous injection in mice as observed by PACT. Following oral administration,
      P-Pc passed through the intestine harmlessly, and PACT could be used to non
      invasively observe intestine function. When the contrast agent placed under the
      arm of a healthy adult human, a PACT transducer on the top of the arm could
      readily detect P-Pc through the entire 5 cm limb. Thus, the approach of using
      contrast media with extreme absorption at 1064 nm readily enables high quality
      optical imaging in vitro and in vivo in humans at exceptional depths. 

PMID- 27022417
TI  - Preliminary Therapy Evaluation of (225)Ac-DOTA-c(RGDyK) Demonstrates that
      Cerenkov Radiation Derived from (225)Ac Daughter Decay Can Be Detected by Optical
      Imaging for In Vivo Tumor Visualization.
AB  - The theranostic potential of (225)Ac-based radiopharmaceuticals continues to
      increase as researchers seek innovative ways to harness the nuclear decay of this
      radioisotope for therapeutic and imaging applications. This communication
      describes the evaluation of (225)Ac-DOTA-c(RGDyK) in both biodistribution and
      Cerenkov luminescence imaging (CLI) studies. Initially, La-DOTA-c(RGDyK) was
      prepared as a non-radioactive surrogate to evaluate methodologies that would
      contribute to an optimized radiochemical synthetic strategy and estimate the
      radioactive conjugate's affinity for alphavbeta3, using surface plasmon resonance
      spectroscopy. Surface plasmon resonance spectroscopy studies revealed the IC50
      and Ki of La-DOTA-c(RGDyK) to be 33 +/- 13 nM and 26 +/- 11 nM, respectively, and
      suggest that the complexation of the La(3+) ion to the conjugate did not
      significantly alter integrin binding. Furthermore, use of this surrogate allowed
      optimization of radiochemical synthesis strategies to prepare (225)Ac-DOTA
      c(RGDyK) with high radiochemical purity and specific activity similar to other
      (225)Ac-based radiopharmaceuticals. This radiopharmaceutical was highly stable in
      vitro. In vivo biodistribution studies confirmed the radiotracer's ability to
      target alphavbeta3 integrin with specificity; specificity was detected in tumor
      bearing animals using Cerenkov luminescence imaging. Furthermore, tumor growth
      control was achieved using non-toxic doses of the radiopharmaceutical in U87mg
      tumor-bearing nude mice. To our knowledge, this is the first report to describe
      the CLI of alphavbeta3 (+) tumors in live animals using the daughter products
      derived from (225)Ac decay in situ. This concept holds promise to further enhance
      development of targeted alpha particle therapy. 

PMID- 27022418
TI  - DNA Nanotechnology for Cancer Therapy.
AB  - DNA nanotechnology is an emerging and exciting field, and represents a forefront
      frontier for the biomedical field. The specificity of the interactions between
      complementary base pairs makes DNA an incredible building material for
      programmable and very versatile two- and three-dimensional nanostructures called
      DNA origami. Here, we analyze the DNA origami and DNA-based nanostructures as a
      drug delivery system. Besides their physical-chemical nature, we dissect the
      critical factors such as stability, loading capability, release and
      immunocompatibility, which mainly limit in vivo applications. Special attention
      was dedicated to highlighting the boundaries to be overcome to bring DNA
      nanostructures closer to the bedside of patients. 

PMID- 27022419
TI  - Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent
      Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of
      Thrombosis.
AB  - RATIONALE: Myocardial infarction and stroke are leading causes of
      morbidity/mortality. The typical underlying pathology is the formation of
      thrombi/emboli and subsequent vessel occlusion. Systemically administered
      fibrinolytic drugs are the most effective pharmacological therapy. However,
      bleeding complications are relatively common and this risk as such limits their
      broader use. Furthermore, a rapid non-invasive imaging technology is not
      available. Thereby, many thrombotic events are missed or only diagnosed when
      ischemic damage has already occurred. OBJECTIVE: Design and preclinical testing
      of a novel 'theranostic' technology for the rapid non-invasive diagnosis and
      effective, bleeding-free treatment of thrombosis. METHODS AND RESULTS: A newly
      created, innovative theranostic microbubble combines a recombinant fibrinolytic
      drug, an echo-enhancing microbubble and a recombinant thrombus-targeting device
      in form of an activated-platelet-specific single-chain antibody. After initial in
      vitro proof of functionality, we tested this theranostic microbubble both in
      ultrasound imaging and thrombolytic therapy using a mouse model of ferric
      chloride-induced thrombosis in the carotid artery. We demonstrate the reliable
      highly sensitive detection of in vivo thrombi and the ability to monitor their
      size changes in real time. Furthermore, these theranostic microbubbles proofed to
      be as effective in thrombolysis as commercial urokinase but without the
      prolongation of bleeding time as seen with urokinase. CONCLUSIONS: We describe a
      novel theranostic technology enabling simultaneous diagnosis and treatment of
      thrombosis, as well as monitoring of success or failure of thrombolysis. This
      technology holds promise for major progress in rapid diagnosis and bleeding-free
      thrombolysis thereby potentially preventing the often devastating consequences of
      thrombotic disease in many patients.

PMID- 27022420
TI  - Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent
      Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy.
AB  - Cell sheet technology opens new perspectives in tissue regeneration therapy by
      providing readily implantable, scaffold-free 3D tissue constructs. Many studies
      have focused on the therapeutic effects of cell sheet implantation while
      relatively little attention has concerned the fate of the implanted cells in
      vivo. The aim of the present study was to track longitudinally the cells
      implanted in the cell sheets in vivo in target tissues. To this end we (i)
      endowed bone marrow-derived mesenchymal stem cells (BMMSCs) with imaging
      properties by double labeling with fluorescent and magnetic tracers, (ii) applied
      BMMSC cell sheets to a digestive fistula model in mice, (iii) tracked the BMMSC
      fate in vivo by MRI and probe-based confocal laser endomicroscopy (pCLE), and
      (iv) quantified healing of the fistula. We show that image-guided longitudinal
      follow-up can document both the fate of the cell sheet-derived BMMSCs and their
      healing capacity. Moreover, our theranostic approach informs on the mechanism of
      action, either directly by integration of cell sheet-derived BMMSCs into the host
      tissue or indirectly through the release of signaling molecules in the host
      tissue. Multimodal imaging and clinical evaluation converged to attest that cell
      sheet grafting resulted in minimal clinical inflammation, improved fistula
      healing, reduced tissue fibrosis and enhanced microvasculature density. At the
      molecular level, cell sheet transplantation induced an increase in the expression
      of anti-inflammatory cytokines (TGF-beta2 and IL-10) and host intestinal growth
      factors involved in tissue repair (EGF and VEGF). Multimodal imaging is useful
      for tracking cell sheets and for noninvasive follow-up of their regenerative
      properties. 

PMID- 27022422
TI  - Correction in author affiliation.
AB  - [This corrects the article DOI: 10.5489/cuaj.10095.]. 

PMID- 27022421
TI  - Folate-modified Chitosan Nanoparticles Containing the IP-10 Gene Enhance Melanoma
      specific Cytotoxic CD8(+)CD28(+) T Lymphocyte Responses.
AB  - BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) has great
      potential for the treatment of some malignant cancers. Therefore, augmenting the
      responses of tumor-specific CTLs is significant for the adoptive immunotherapy of
      melanoma. This study aimed to investigate the anti-tumor response of a
      combination therapy employing folate-modified chitosan nanoparticles containing
      IP-10 (interferon-gamma-inducible protein-10) plus melanoma TRP2-specific
      CD8(+)CD28(+) T cells. METHODS: We prepared folate-modified chitosan
      nanoparticles containing the mouse IP-10 gene (FA-CS-mIP-10), and induced
      melanoma TRP2-specific CD8(+)CD28(+) T cells by co-culturing them with artificial
      antigen-presenting cells. B16-bearing mice were treated with FA-CS-mIP-10,
      melanoma TRP2-specific CD8(+)CD28(+) T cells, a combination of both, and the
      saline control. Tumor volumes and the survival time of mice were recorded. The
      proportion of myeloid-derived suppressor cells (MDSCs) infiltrating the tumor
      microenvironment and regulatory T cells (Tregs) in the spleen was analyzed by
      flow cytometry. We also detected the proliferation and angiogenesis of tumors by
      immunohistochemistry and apoptosis by TUNEL. RESULTS: The combination therapy
      inhibited the progression of melanoma in vivo. Compared with other treatments, it
      more efficiently inhibited tumor growth and increased the survival time of mice.
      After treatment with combination therapy, the proportion of MDSCs and Tregs
      decreased, while the percentage of CXCR3(+)CD8(+) T cells increased. Furthermore,
      combination therapy inhibited proliferation and promoted apoptosis of tumor cells
      and significantly inhibited tumor angiogenesis in vivo. CONCLUSION: We describe a
      novel strategy for improving the anti-tumor response of CD8(+)CD28(+) CTLs by
      combining them with FA-CS-mIP-10 nanoparticles.

PMID- 27022423
TI  - Correction in author list.
AB  - [This corrects the article on p. e731 in vol. 9, PMID: 26664509.]. 

PMID- 27022424
TI  - [Diagnostic contribution of exploratory cervicotomy: retrospective study of 300
      cases].

PMID- 27022425
TI  - Lupus nephritis is associated with poor pregnancy outcomes in pregnant SLE
      patients in Cape Town: a retrospective analysis.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a multi-system auto-immune
      disease common in females of child-bearing age. The effect of pregnancy on SLE
      and vice versa have not been well characterised in Africans. The aim of this
      study is to describe the pregnancy outcomes of patients with SLE presenting to
      the maternity department of Groote Schuur Hospital, Cape Town. METHODS: This
      study was designed as a retrospective review of records of pregnant women known
      with SLE and followed-up at the maternity section of Groote Schuur Hospital. The
      duration of survey was from the 1(st) January 2003 to 31(st) December 2013.
      RESULTS: There were 61 pregnancies reviewed in 49 patients; 80.3% of the
      pregnancies were in patients of mixed ancestry and the rest (19.7%) in black
      African patients. The mean age at presentation of the current pregnancy was 27.2
      +/- 5.0 years. Mean gestational age at presentation and delivery was 13.0 +/- 6.0
      weeks and 28.9 +/- 9.8 weeks respectively and 47.5% of the pregnancies were in
      patients with lupus nephritis (LN). Thirty nine (63.9%) pregnancies reached the
      third trimester and 11.5% of all pregnancies ended in the first trimester. There
      was a lower number of live births to mothers of African ancestry than to those of
      mixed ancestry (p = 0.001). In 55.7% of the pregnancies, no flare was reported
      while a renal flare was reported in 23%. Pregnancies in patients with LN had
      higher frequencies of flares (58.6% vs 31.3%; p = 0.032), pre-eclampsia (34.5% vs
      12.5%; p = 0.041), longer stay in hospital (12.0 +/- 9.1 days vs 6.1 +/- 5.1
      days; p = 0.004) and low birth weight babies (1.94 +/- 1.02 kg vs 2.55 +/- 0.95
      kg; p = 0.046) than in patients without LN. Only 36 (59%) of the neonates were
      discharged home alive and of these 2 (5.6%) were to mothers of black African
      ancestry (p = 0.001). CONCLUSION: Increased lupus activity in pregnant SLE
      patients may account for the increased deaths of neonates born to SLE mothers.
      Patients of black African descent and those with LN tend to have a poorer
      outcome. A multi-disciplinary approach to the management of SLE patients (of
      child-bearing age or pregnant) needs to be further assessed for better outcomes.

PMID- 27022426
TI  - [Results of advanced cataract tunnel surgery: about 262 cases performed at CHR
      Banfora (Burkina Faso)].

PMID- 27022427
TI  - [Cardiovascular risk factors in systemic lupus erythematosus].

PMID- 27022428
TI  - [Favique ringworm treated with terbinafine in a child of 11 years].

PMID- 27022429
TI  - [Squamous cell carcinoma of the cervix relapsing as an isolated pulmonary
      metastasis: report of a case and review of literature].

PMID- 27022430
TI  - [Obesity, physical activity and sedentary time among school adolescents aged 15
      to 18 years in the city of Sfax (Tunisia)].

PMID- 27022431
TI  - [Traumatic rupture of the posterior tibial tendon occurring during a closed
      fracture of the ankle: report of a case].

PMID- 27022432
TI  - [Percutaneous sacroiliac screw fixation].

PMID- 27022433
TI  - [Are HVC patients on hemodialysis really difficult to treat patients?].

PMID- 27022434
TI  - [Soft tissue sarcoma: a report of 33 cases].

PMID- 27022435
TI  - Comment on "MicroRNA-208a Silencing Attenuates Doxorubicin Induced Myocyte
      Apoptosis and Cardiac Dysfunction".

PMID- 27022436
TI  - Hydrogen Sulfide Improves Vascular Calcification in Rats by Inhibiting
      Endoplasmic Reticulum Stress.
AB  - In this study, the vitamin D3 plus nicotine (VDN) model of rats was used to prove
      that H2S alleviates vascular calcification (VC) and phenotype transformation of
      vascular smooth muscle cells (VSMC). Besides, H2S can also inhibit endoplasmic
      reticulum stress (ERS) of calcified aortic tissues. The effect of H2S on
      alleviating VC and phenotype transformation of VSMC can be blocked by TM, while
      PBA also alleviated VC and phenotype transformation of VSMC that was similar to
      the effect of H2S. These results suggest that H2S may alleviate rat aorta VC by
      inhibiting ERS, providing new target and perspective for prevention and treatment
      of VC. 

PMID- 27022437
TI  - Role of nuclear receptors in breast cancer stem cells.
AB  - The recapitulation of primary tumour heterogenity and the existence of a minor
      sub-population of cancer cells, capable of initiating tumour growth in xenografts
      on serial passages, led to the hypothesis that cancer stem cells (CSCs) exist.
      CSCs are present in many tumours, among which is breast cancer. Breast CSCs
      (BCSCs) are likely to sustain the growth of the primary tumour mass, as well as
      to be responsible for disease relapse and metastatic spreading. Consequently,
      BCSCs represent the most significant target for new drugs in breast cancer
      therapy. Both the hypoxic condition in BCSCs biology and pro-inflammatory
      cytokine network has gained increasing importance in the recent past. Breast
      stromal cells are crucial components of the tumours milieu and are a major source
      of inflammatory mediators. Recently, the anti-inflammatory role of some nuclear
      receptors ligands has emerged in several diseases, including breast cancer.
      Therefore, the use of nuclear receptors ligands may be a valid strategy to
      inhibit BCSCs viability and consequently breast cancer growth and disease
      relapse. 

PMID- 27022438
TI  - Homing and migration of mesenchymal stromal cells: How to improve the efficacy of
      cell therapy?
AB  - Mesenchymal stromal cells (MSCs) are currently being investigated for use in a
      wide variety of clinical applications. For most of these applications, systemic
      delivery of the cells is preferred. However, this requires the homing and
      migration of MSCs to a target tissue. Although MSC homing has been described,
      this process does not appear to be highly efficacious because only a few cells
      reach the target tissue and remain there after systemic administration. This has
      been ascribed to low expression levels of homing molecules, the loss of
      expression of such molecules during expansion, and the heterogeneity of MSCs in
      cultures and MSC culture protocols. To overcome these limitations, different
      methods to improve the homing capacity of MSCs have been examined. Here, we
      review the current understanding of MSC homing, with a particular focus on homing
      to bone marrow. In addition, we summarize the strategies that have been developed
      to improve this process. A better understanding of MSC biology, MSC migration and
      homing mechanisms will allow us to prepare MSCs with optimal homing capacities.
      The efficacy of therapeutic applications is dependent on efficient delivery of
      the cells and can, therefore, only benefit from better insights into the homing
      mechanisms. 

PMID- 27022439
TI  - Malaria modeling: In vitro stem cells vs in vivo models.
AB  - The recent development of stem cell research and the possibility of generating
      cells that can be stably and permanently modified in their genome open a broad
      horizon in the world of in vitro modeling. The malaria field is gaining new
      opportunities from this important breakthrough and novel tools were adapted and
      opened new frontiers for malaria research. In addition to the new in vitro
      systems, in recent years there were also significant advances in the development
      of new animal models that allows studying the entire cell cycle of human malaria.
      In this paper, we review the different protocols available to study human
      Plasmodium species either by using stem cell or alternative animal models. 

PMID- 27022440
TI  - Role of adipose-derived stromal cells in pedicle skin flap survival in
      experimental animal models.
AB  - The use of skin flaps in reconstructive surgery is the first-line surgical
      treatment for the reconstruction of skin defects and is essentially considered
      the starting point of plastic surgery. Despite their excellent usability, their
      application includes general surgical risks or possible complications, the
      primary and most common is necrosis of the flap. To improve flap survival,
      researchers have used different methods, including the use of adipose-derived
      stem cells, with significant positive results. In our research we will report the
      use of adipose-derived stem cells in pedicle skin flap survival based on current
      literature on various experimental models in animals. 

PMID- 27022441
TI  - Updates in the pathophysiological mechanisms of Parkinson's disease: Emerging
      role of bone marrow mesenchymal stem cells.
AB  - AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to
      improve Parkinson's disease (PD) pathophysiology. METHODS: MSCs were harvested
      from bone marrow of femoral bones of male rats, grown and propagated in culture.
      Twenty four ovariectomized animals were classified into 3 groups: Group (1) was
      control, Groups (2) and (3) were subcutaneously administered with rotenone for 14
      d after one month of ovariectomy for induction of PD. Then, Group (2) was left
      untreated, while Group (3) was treated with single intravenous dose of bone
      marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of
      the female rats. Serum transforming growth factor beta-1 (TGF-beta1), monocyte
      chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF)
      levels were assayed by ELISA. Brain dopamine DA level was assayed
      fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene
      expression were detected by semi-quantitative real time PCR. Brain survivin
      expression was determined by immunohistochemical procedure. Histopathological
      investigation of brain tissues was also done. RESULTS: BM-MSCs were able to home
      at the injured brains and elicited significant decrease in serum TGF-beta1 (489.7
      +/- 13.0 vs 691.2 +/- 8.0, P < 0.05) and MCP-1 (89.6 +/- 2.0 vs 112.1 +/- 1.9, P
      < 0.05) levels associated with significant increase in serum BDNF (3663 +/- 17.8
      vs 2905 +/- 72.9, P < 0.05) and brain DA (874 +/- 15.0 vs 599 +/- 9.8, P < 0.05)
      levels as well as brain TH (1.18 +/- 0.004 vs 0.54 +/- 0.009, P < 0.05) and
      nestin (1.29 +/- 0.005 vs 0.67 +/- 0.006, P < 0.05) genes expression levels. In
      addition to, producing insignificant increase in the number of positive cells for
      survivin (293.2 +/- 15.9 vs 271.5 +/- 15.9, P > 0.05) expression. Finally, the
      brain sections showed intact histological structure of the striatum as a result
      of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the
      therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic
      actions.

PMID- 27022443
TI  - Metformin revisited: Does this regulator of AMP-activated protein kinase
      secondarily affect bone metabolism and prevent diabetic osteopathy.
AB  - Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop
      skeletal complications or "diabetic osteopathy". These include osteopenia,
      osteoporosis and an increased incidence of low-stress fractures. In this context,
      it is important to evaluate whether current anti-diabetic treatments can
      secondarily affect bone metabolism. Adenosine monophosphate-activated protein
      kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the
      cellular energy status; recent evidence suggests a critical role for AMPK in bone
      homeostasis. In addition, AMPK activation is believed to mediate most clinical
      effects of the insulin-sensitizer metformin. Over the past decade, several
      research groups have investigated the effects of metformin on bone, providing a
      considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as
      clinical evidence for an anabolic action of metformin on bone. However, two
      caveats should be kept in mind when considering metformin treatment for a patient
      with type 2 DM at risk for diabetic osteopathy. In the first place, metformin
      should probably not be considered an anti-osteoporotic drug; it is an insulin
      sensitizer with proven macrovascular benefits that can secondarily improve bone
      metabolism in the context of DM. Secondly, we are still awaiting the results of
      randomized placebo-controlled studies in humans that evaluate the effects of
      metformin on bone metabolism as a primary endpoint. 

PMID- 27022442
TI  - Low serum amylase and obesity, diabetes and metabolic syndrome: A novel
      interpretation.
AB  - For the last decade, low serum amylase (hypoamylasemia) has been reported in
      certain common cardiometabolic conditions such as obesity, diabetes (regardless
      of type), and metabolic syndrome, all of which appear to have a common etiology
      of insufficient insulin action due to insulin resistance and/or diminished
      insulin secretion. Some clinical studies have shown that salivary amylase may be
      preferentially decreased in obese individuals, whereas others have revealed that
      pancreatic amylase may be preferentially decreased in diabetic subjects with
      insulin dependence. Despite this accumulated evidence, the clinical relevance of
      serum, salivary, and pancreatic amylase and the underlying mechanisms have not
      been fully elucidated. In recent years, copy number variations (CNVs) in the
      salivary amylase gene (AMY1), which range more broadly than the pancreatic
      amylase gene (AMY2A and AMY2B), have been shown to be well correlated with
      salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low
      salivary amylase, was associated with insulin resistance, obesity, low taste
      perception/satiety, and postprandial hyperglycemia through impaired insulin
      secretion at early cephalic phase. In most populations, insulin-dependent
      diabetes is less prevalent (minor contribution) compared with insulin-independent
      diabetes, and obesity is highly prevalent compared with low body weight.
      Therefore, obesity as a condition that elicits cardiometabolic diseases relating
      to insulin resistance (major contribution) may be a common determinant for low
      serum amylase in a general population. In this review, the novel interpretation
      of low serum, salivary, and pancreas amylase is discussed in terms of major
      contributions of obesity, diabetes, and metabolic syndrome. 

PMID- 27022444
TI  - Infantile onset diabetes mellitus in developing countries - India.
AB  - Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in
      children. Infants with onset of diabetes mellitus (DM) at age less than one year
      are likely to have transient or permanent neonatal DM or rarely type 1 diabetes.
      Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene
      mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases
      present with diabetic keto acidosis at the onset. Missed diagnosis was common in
      infants with diabetes (67%). Potassium channel mutation with sulphonylurea
      responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison
      syndrome is the common type in syndromic diabetes. Developmental delay and
      seizures were the associated co-morbid states. Genetic diagnosis has made a
      phenomenal change in the management of IODM. Switching from subcutaneous insulin
      to oral hypoglycemic drugs is a major clinical breakthrough in the management of
      certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5%
      during follow-up from Indian studies. This article is a review of neonatal
      diabetes and available literature on IODM from India. 

PMID- 27022446
TI  - Relevance of fecal calprotectin and lactoferrin in the post-operative management
      of inflammatory bowel diseases.
AB  - The role of fecal lactoferrin and calprotectin has been extensively studied in
      many areas of inflammatory bowel disease (IBD) patients' management. The post
      operative setting in both Crohn's disease (CD) and ulcerative colitis (UC)
      patients has been less investigated although few promising results come from
      small, cross-sectional studies. Therefore, the current post-operative management
      still requires endoscopy 6-12 mo after intestinal resection for CD in order to
      exclude endoscopic recurrence and plan the therapeutic strategy. In patients who
      underwent restorative proctocolectomy, endoscopy is required whenever symptoms
      includes the possibility of pouchitis. There is emerging evidence that fecal
      calprotectin and lactoferrin are useful surrogate markers of inflammation in the
      post-operative setting, they correlate with the presence and severity of
      endoscopic recurrence according to Rutgeerts' score and possibly predict the
      subsequent clinical recurrence and response to therapy in CD patients. Similarly,
      fecal markers show a good correlation with the presence of pouchitis, as
      confirmed by endoscopy in operated UC patients. Fecal calprotectin seems to be
      able to predict the short-term development of pouchitis in asymptomatic patients
      and to vary according to response to medical treatment. The possibility of both
      fecal markers to used in the routine clinical practice for monitoring IBD
      patients in the post-operative setting should be confirmed in multicentric
      clinical trial with large sample set. An algorithm that can predict the optimal
      use and timing of fecal markers testing, the effective need and timing of
      endoscopy and the cost-effectiveness of these as a strategy of care would be of
      great interest. 

PMID- 27022445
TI  - Assessment of lymph node involvement in colorectal cancer.
AB  - Lymph node metastasis informs prognosis and is a key factor in deciding further
      management, particularly adjuvant chemotherapy. It is core to all contemporary
      staging systems, including the widely used tumor node metastasis staging system.
      Patients with node-negative disease have 5-year survival rates of 70%-80%,
      implying a significant minority of patients with occult lymph node metastases
      will succumb to disease recurrence. Enhanced staging techniques may help to
      identify this subset of patients, who might benefit from further treatment.
      Obtaining adequate numbers of lymph nodes is essential for accurate staging.
      Lymph node yields are affected by numerous factors, many inherent to the patient
      and the tumour, but others related to surgical and histopathological practice.
      Good lymph node recovery relies on close collaboration between surgeon and
      pathologist. The optimal extent of surgical resection remains a subject of
      debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high
      arterial ligation and complete mesocolic excision are amongst the surgical
      techniques with plausible oncological bases, but which are not supported by the
      highest levels of evidence. With further development and refinement, intra
      operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to
      the optimum extent of lymphadenectomy, but in its present form, it is beset by
      false negatives, skip lesions and failures to identify a sentinel node. Once
      resected, histopathological assessment of the surgical specimen can be improved
      by thorough dissection techniques, step-sectioning of tissue blocks and
      immunohistochemistry. More recently, molecular methods have been employed. In
      this review, we consider the numerous factors that affect lymph node yields,
      including the impact of the surgical and histopathological techniques. Potential
      future strategies, including the use of evolving technologies, are also
      discussed. 

PMID- 27022447
TI  - Current perspectives on pancreatic serous cystic neoplasms: Diagnosis, management
      and beyond.
AB  - Pancreatic cystic neoplasms have been increasingly recognized recently.
      Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic
      neoplasms are uncommon benign lesions that are usually asymptomatic and found
      incidentally. Despite overall low risk of malignancy, these pancreatic cysts
      still generate anxiety, leading to intensive medical investigations with
      considerable financial cost to health care systems. This review discusses the
      general background of serous cystic neoplasms, including epidemiology and
      clinical characteristics, and provides an updated overview of diagnostic
      approaches based on clinical features, relevant imaging studies and new findings
      that are being discovered pertaining to diagnostic evaluation. We also concisely
      discuss and propose management strategies for better quality of life. 

PMID- 27022448
TI  - Duodenal adenocarcinoma: Advances in diagnosis and surgical management.
AB  - Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity,
      previous studies have traditionally combined duodenal adenocarcinoma (DA) with
      either other periampullary cancers or small bowel adenocarcinomas, limiting the
      available data to guide treatment decisions. Nevertheless, management primarily
      involves complete surgical resection when technically feasible. Surgery may
      require pancreaticoduodenectomy or segmental duodenal resection; either are
      acceptable options as long as negative margins are achievable and an adequate
      lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are
      important components of multi-modality treatment for patients at high risk of
      recurrence. Further research would benefit from multi-institutional trials that
      do not combine DA with other periampullary or small bowel malignancies. The
      purpose of this article is to perform a comprehensive review of DA with special
      focus on the surgical management and principles. 

PMID- 27022449
TI  - Adhesive small bowel adhesions obstruction: Evolutions in diagnosis, management
      and prevention.
AB  - Intra-abdominal adhesions following abdominal surgery represent a major unsolved
      problem. They are the first cause of small bowel obstruction. Diagnosis is based
      on clinical evaluation, water-soluble contrast follow-through and computed
      tomography scan. For patients presenting no signs of strangulation, peritonitis
      or severe intestinal impairment there is good evidence to support non-operative
      management. Open surgery is the preferred method for the surgical treatment of
      adhesive small bowel obstruction, in case of suspected strangulation or after
      failed conservative management, but laparoscopy is gaining widespread acceptance
      especially in selected group of patients. "Good" surgical technique and anti
      adhesive barriers are the main current concepts of adhesion prevention. We
      discuss current knowledge in modern diagnosis and evolving strategies for
      management and prevention that are leading to stratified care for patients. 

PMID- 27022450
TI  - Doppler-guided hemorrhoidal dearterialization/transanal hemorrhoidal
      dearterialization: Technical evolution and outcomes after 20 years.
AB  - In the setting of Hemorrhoidal Disease treatment, the option of conventional
      hemorrhoidectomy is highly effective, but it is still associated with
      postoperative pain and discomfort. For this reason, technical alternatives have
      been developed in order to reduce complications and to provide better
      postoperative recovery. To accomplish this aim, non-excisional techniques such as
      stapled hemorrhoidectomy and Doppler-guided hemorrhoidal ligation have been
      introduced into clinical practice with high expectations. The aim of this article
      is to revise the literature about transanal hemorrhoidal dearterialization
      technique in the treatment of hemorrhoidal disease, looking into its evolution,
      results and possible benefits over other modalities of surgical treatment. The
      literature review showed that Doppler-guided hemorrhoidal dearterialization is a
      safe and effective method to treat grades II to IV hemorrhoidal disease. Outcomes
      in patients presenting prolapse are satisfactory and the association of anopexy
      is an important aspect of this operation. Anal physiology disturbances are rarely
      observed and mainly transitory. This technique is an excellent option for every
      patient, especially in those with previous anal surgeries and in patients with
      previous alterations of fecal continence, when an additional procedure might
      represent a risk of definitive incontinence. 

PMID- 27022451
TI  - Long-term results after revisions of failed primary vertical banded gastroplasty.
AB  - AIM: To compare the results after revision of primary vertical banded
      gastroplasty (Re-VBG) and conversion to sleeve gastrectomy (cSG) or gastric
      bypass (cRYGB). METHODS: In this retrospective single-center study, all patients
      with a failed VBG who underwent revisional surgery were included. Medical charts
      were reviewed and additional postal questionnaires were sent to update follow-up.
      Weight loss, postoperative complications and long-term outcome were assessed.
      RESULTS: A total 152 patients were included in this study, of which 21 underwent
      Re-VBG, 16 underwent cSG and 115 patients underwent cRYGB. Sixteen patients
      necessitated a second revisional procedure. No patients were lost-to-follow-up.
      Two patients deceased during the follow-up period, 23 patients did not return the
      questionnaire. Main reasons for revision were dysphagia/vomiting, weight regain
      and insufficient weight loss. Excess weight loss (%EWL) after Re-VBG, cSG and
      cRYGB was, respectively, 45%, 57% and 72%. Eighteen patients (11.8%) reported
      postoperative complications and 27% reported long-term complaints. CONCLUSION: In
      terms of additional weight loss, postoperative complaints and reintervention
      rate, Roux-en-Y gastric bypass seems feasible as a revision for a failed VBG.

PMID- 27022452
TI  - Changes over time in milk test results following pancreatectomy.
AB  - AIM: To investigate changes over time in, and effects of sealing technology on,
      milk test results following pancreatectomy. METHODS: From April 2008 to October
      2013, 66 pancreatic resections were performed at the Iwakuni Clinical Center. The
      milk test has been routinely conducted at the institute whenever possible during
      pancreatectomy. The milk test comprises the following procedure: A nasogastric
      tube is inserted until the third portion of the duodenum, followed by injection
      of 100 mL of milk through the tube. If a chyle leak is present, the patient tests
      positive in this milk test based on the observation of a white milky discharge.
      Positive milk test rates, leakage sites, and chylous ascites incidence were
      examined. LigaSureTM (LS; Covidien, Dublin, Ireland), a vessel-sealing device, is
      routinely used in pancreatectomy. Positive milk test rates before and after use
      of LS, as well as drain discharge volume at the 2(nd) and 3(rd) postoperative
      days, were compared retrospectively. Finally, positive milk test rates and
      chylous ascites incidence were compared with the results of a previous report.
      RESULTS: Fifty-nine milk tests were conducted during pancreatectomy. The positive
      milk test rate for all pancreatectomy cases was 13.6% (8 of 59 cases). One case
      developed postoperative chylous ascites (2.1% among the pancreatoduedenectomy
      cases and 1.7% among all pancreatectomies). Positive rates by procedure were
      12.8% for pancreatoduodenectomy and 22.2% for distal pancreatectomy. Positive
      rates by disease were 17.9% for pancreatic and 5.9% for biliary diseases. When
      comparing results from before and after use of LS, positive milk test rates in
      pancreatoduodenectomy were 13.0% before and 12.5% after, while those in distal
      pancreatectomy were 33.3% and 0%. Drainage volume tended to decrease when LS was
      used on the 3(rd) postoperative day (volumes were 424 +/- 303 mL before LS and
      285 +/- 185 mL after, P = 0.056). Both chylous ascites incidence and positive
      milk test rates decreased slightly compared with those rates from the previous
      study. CONCLUSION: Positive milk test rates and chylous ascites incidence
      decreased over time. Sealing technology may thus play an important role in
      preventing postoperative chylous ascites.

PMID- 27022454
TI  - Fibrin sealant use in pilonidal sinus: Systematic review.
AB  - AIM: To review the current data about the success rates of fibrin sealant use in
      pilonidal disease. METHODS: Fibrin sealant can be used for different purposes in
      pilonidal sinus treatment, such as filling in the sinus tracts, covering the open
      wound after excision and lay-open treatment, or obliterating the subcutaneous
      dead space before skin closure. We searched Pubmed, Google-Scholar, Ebsco-Host,
      clinicaltrials, and Cochrane databases and found nine studies eligible for
      analysis; these studies included a total of 217 patients (84% male, mean age 24.2
      +/- 7.8). RESULTS: In cases where fibrin sealant was used to obliterate the
      subcutaneous dead space, there was no reduction in wound complication rates (9.8%
      vs 14.6%, P = 0.48). In cases where sealant was used to cover the laid-open area,
      the wound healing time and patient comfort were reported better than in previous
      studies (mean 17 d, 88% satisfaction). When fibrin sealant was used to fill the
      sinus tracts, the recurrence rate was around 20%, despite the highly selected
      grouping of patients. CONCLUSION: Consequently, using fibrin sealant to decrease
      the risk of seroma formation was determined to be an ineffective course of
      action. It was not advisable to fill the sinus tracts with fibrin sealant because
      it was not superior to other cost-effective and minimally invasive treatments.
      New comparative studies can be conducted to confirm the results of sealant use in
      covering the laid-open area.

PMID- 27022453
TI  - Primary squamous cell carcinoma of the rectum: An update and implications for
      treatment.
AB  - AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and
      management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review
      was conducted according to the preferred reporting items for Systematic Reviews
      and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was
      performed with the reference list of selected articles reviewed to ensure all
      relevant publications were captured. The search strategy was limited to the
      English language, spanning from 1946 to 2015. A qualitative analysis was
      undertaken examining patient demographics, clinical presentation, diagnosis,
      staging, treatment and outcome. The quantitaive analysis was limited to data
      extracted on treatment and outcomes including radiological, clinical and
      pathological complete response where available. The narrative and quantitative
      review were synthesised in concert. RESULTS: The search identified 487 articles
      in total with 79 included in the qualitative review. The quantitative analysis
      involved 63 articles, consisting of 43 case reports and 20 case series with a
      total of 142 individual cases. The underlying pathogenesis of rectal SCC while
      unclear, continues to be defined, with increasing evidence of a metaplasia
      dysplasia-carcinoma sequence and a possible role for human papilloma virus in
      this progression. The presentation is similar to rectal adenocarcinoma, with a
      diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC's are in fact
      an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this
      distinction. Staging is most accurately reflected by the tumour-node-metastasis
      classification for rectal adenocarcinoma. It involves examining locoregional
      disease by way of magnetic resonance imaging and/or endorectal ultrasound, with
      systemic spread excluded by way of computed tomography. Positron emission
      tomography is integral in the workup to exclude an external site of primary SCC
      with metastasis to the rectum. While the optimal treatment remains as yet
      undefined, recent studies have demonstrated a global shift away from surgery
      towards definitive chemoradiotherapy as primary treatment. Pooled overall
      survival was calculated to be 86% in patients managed with chemoradiation
      compared with 48% for those treated traditionally with surgery. Furthermore,
      local recurrence and metastatic rates were 25% vs 10% and 30% vs 13% for the
      chemoradiation vs conventional treatment cohorts. CONCLUSION: The changing
      paradigm in the treatment of rectal SCC holds great promise for improved outcomes
      in this rare disease.

PMID- 27022455
TI  - Post-operative abdominal complications in Crohn's disease in the biological era:
      Systematic review and meta-analysis.
AB  - AIM: To perform a systematic review and meta-analysis on post-operative
      complications after surgery for Crohn's disease (CD) comparing biological with no
      therapy. METHODS: PubMed, Medline and Embase databases were searched to identify
      studies comparing post-operative outcomes in CD patients receiving biological
      therapy and those who did not. A meta-analysis with a random-effects model was
      used to calculate pooled odds ratios (OR) and confidence intervals (CI) for each
      outcome measure of interest. RESULTS: A total of 14 studies were included for
      meta-analysis, comprising a total of 5425 patients with CD 1024 (biological
      treatment, 4401 control group). After biological therapy there was an increased
      risk of total infectious complications (OR = 1.52; 95%CI: 1.14-2.03, 8 studies)
      and wound infection (OR = 1.73; 95%CI: 1.12-2.67; P = 0.01, 7 studies). There was
      no increased risk for other complications including anastomotic leak (OR = 1.19;
      95%CI: 0.82-1.71; P = 0.26), abdominal sepsis (OR = 1.22; 95%CI: 0.87-1.72; P =
      0.25) and re-operation (OR = 1.12; 95%CI: 0.81-1.54; P = 0.46) in patients
      receiving biological therapy. CONCLUSION: Pre-operative use of anti-TNF-alpha
      therapy may increase risk of post-operative infectious complications after
      surgery for CD and in particular wound related infections.

PMID- 27022456
TI  - Lipoprotein abnormalities in South Asians and its association with cardiovascular
      disease: Current state and future directions.
AB  - South Asians have a high prevalence of coronary heart disease (CHD) and suffer
      from early-onset CHD compared to other ethnic groups. Conventional risk factors
      may not fully explain this increased CHD risk in this population. Indeed, South
      Asians have a unique lipid profile which may predispose them to premature CHD.
      Dyslipidemia in this patient population seems to be an important contributor to
      the high incidence of coronary atherosclerosis. The dyslipidemia in South Asians
      is characterized by elevated levels of triglycerides, low levels of high-density
      lipoprotein (HDL) cholesterol, elevated lipoprotein(a) levels, and a higher
      atherogenic particle burden despite comparable low-density lipoprotein
      cholesterol levels compared with other ethnic subgroups. HDL particles also
      appear to be smaller, dysfunctional, and proatherogenic in South Asians. Despite
      the rapid expansion of the current literature with better understanding of the
      specific lipid abnormalities in this patient population, studies with adequate
      sample sizes are needed to assess the significance and contribution of a given
      lipid parameter on overall cardiovascular risk in this population. Specific
      management goals and treatment thresholds do not exist for South Asians because
      of paucity of data. Current treatment recommendations are mostly extrapolated
      from Western guidelines. Lastly, large, prospective studies with outcomes data
      are needed to assess cardiovascular benefit associated with various lipid
      lowering therapies (including combination therapy) in this patient population. 

PMID- 27022457
TI  - Exercise oscillatory ventilation: Mechanisms and prognostic significance.
AB  - Alteration in breathing patterns characterized by cyclic variation of ventilation
      during rest and during exercise has been recognized in patients with advanced
      heart failure (HF) for nearly two centuries. Periodic breathing (PB) during
      exercise is known as exercise oscillatory ventilation (EOV) and is characterized
      by the periods of hyperpnea and hypopnea without interposed apnea. EOV is a non
      invasive parameter detected during submaximal cardiopulmonary exercise testing.
      Presence of EOV during exercise in HF patients indicates significant impairment
      in resting and exercise hemodynamic parameters. EOV is also an independent risk
      factor for poor prognosis in HF patients both with reduced and preserved ejection
      fraction irrespective of other gas exchange variables. Circulatory delay,
      increased chemosensitivity, pulmonary congestion and increased ergoreflex
      signaling have been proposed as the mechanisms underlying the generation of EOV
      in HF patients. There is no proven treatment of EOV but its reversal has been
      noted with phosphodiesterase inhibitors, exercise training and acetazolamide in
      relatively small studies. In this review, we discuss the mechanistic basis of PB
      during exercise and the clinical implications of recognizing PB patterns in
      patients with HF. 

PMID- 27022458
TI  - Prediction of atrial fibrillation development and progression: Current
      perspectives.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice.
      Several conventional and novel predictors of AF development and progression (from
      paroxysmal to persistent and permanent types) have been reported. The most
      important predictor of AF progression is possibly the arrhythmia itself. The
      electrical, mechanical and structural remodeling determines the perpetuation of
      AF and the progression from paroxysmal to persistent and permanent forms. Common
      clinical scores such as the hypertension, age >= 75 years, transient ischemic
      attack or stroke, chronic obstructive pulmonary disease, and heart failure and
      the congestive heart failure, hypertension, age >= 75 years, diabetes mellitus,
      stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category
      scores as well as biomarkers related to inflammation may also add important
      information on this topic. There is now increasing evidence that even in patients
      with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a
      structural atrial disease which has recently been defined and described as
      fibrotic atrial cardiomyopathy. Fibrosis results from a broad range of factors
      related to AF inducing pathologies such as cell stretch, neurohumoral activation,
      and oxidative stress. The extent of fibrosis as detected either by late
      gadolinium enhancement-magnetic resonance imaging or electroanatomic voltage
      mapping may guide the therapeutic approach based on the arrhythmia substrate. The
      knowledge of these risk factors may not only delay arrhythmia progression, but
      also reduce the arrhythmia burden in patients with first detected AF. The present
      review highlights on the conventional and novel risk factors of development and
      progression of AF. 

PMID- 27022459
TI  - Tilt table test today - state of the art.
AB  - A tilt table test (TTT) is an inexpensive, noninvasive tool for the differential
      diagnosis of syncope and orthostatic intolerance and has good diagnostic yield.
      The autonomic system malfunction which underlines the reflex syncope is
      manifested as either hypotension or bradycardia, while an orthostatic challenge
      is applied. The timing of the response to the orthostatic challenge, as well as
      the predominant component of the response help to differentiate between various
      forms of neurocardiogenic syncope, orthostatic hypotension and non-cardiovascular
      conditions (e.g., pseudosyncope). Medications, such as isoproterenol and
      nitrates, may increase TTT sensitivity. Sublingual nitrates are easiest to
      administer without the need of venous access. TTT can be combined with carotid
      sinus massage to evaluate carotid sinus hypersensitivity, which may not be
      present in supine position. TTT is not useful to access the response to
      treatment. Recently, implantable loop recorders (ILR) have been used to document
      cardioinhibitory reflex syncope, because pacemakers are beneficial in many of
      these patients, especially those over 45 years of age. The stepwise use of both
      TTT and ILR is a promising approach in these patients. Recently, TTT has been
      used for indications other than syncope, such as assessment of autonomic function
      in Parkinson's disease and its differentiation from multiple system atrophy. 

PMID- 27022460
TI  - Clinical outcomes of combined flow-pressure drop measurements using newly
      developed diagnostic endpoint: Pressure drop coefficient in patients with
      coronary artery dysfunction.
AB  - AIM: To combine pressure and flow parameter, pressure drop coefficient (CDP) will
      result in better clinical outcomes in comparison to the fractional flow reserve
      (FFR) group. METHODS: To test this hypothesis, a comparison was made between the
      FFR < 0.75 and CDP > 27.9 groups in this study, for the major adverse cardiac
      events [major adverse cardiac events (MACE): Primary outcome] and patients'
      quality of life (secondary outcome). Further, a comparison was also made between
      the survival curves for the FFR < 0.75 and CDP > 27.9 groups. Two-tailed chi (2)
      test proportions were performed for the comparison of primary and secondary
      outcomes. Kaplan-Meier survival analysis was performed to compare the survival
      curves of FFR < 0.75 and CDP > 27.9 groups (MedcalcV10.2, Mariakerke, Belgium).
      Results were considered statistically significant for P < 0.05. RESULTS: The
      primary outcomes (%MACE) in the FFR < 0.75 group (20%, 4 out of 20) was not
      statistically different (P = 0.24) from the %MACE occurring in CDP > 27.9 group
      (8.57%, 2 out of 35). Noteworthy is the reduction in the %MACE in the CDP > 27.9
      group, in comparison to the FFR < 0.75 group. Further, the secondary outcomes
      were not statistically significant between the FFR < 0.75 and CDP > 27.9 groups.
      Survival analysis results suggest that the survival time for the CDP > 27.9 group
      (n = 35) is significantly higher (P = 0.048) in comparison to the survival time
      for the FFR < 0.75 group (n = 20). The results remained similar for a FFR = 0.80
      cut-off. CONCLUSION: Based on the above, CDP could prove to be a better
      diagnostic end-point for clinical revascularization decision-making in the
      cardiac catheterization laboratories.

PMID- 27022461
TI  - Typical rise and fall of troponin in (peri-procedural) myocardial infarction: A
      systematic review.
AB  - AIM: To identify the typical shape of the rise and fall curve of troponin (Tn)
      following the different types of myocardial infarction (MI). METHODS: We
      conducted a systematic search in PubMed and Embase including all studies which
      focused on the kinetics of Tn in MI type 1, type 4 and type 5. Tn levels were
      standardized using the 99(th) percentile, a pooled mean with 95%CI was calculated
      from the weighted means for each time point until 72 h. RESULTS: A total of 34 of
      the 2528 studies identified in the systematic search were included. The maximum
      peak level of the Tn was seen after 6 h after successful reperfusion of an acute
      MI, after 12 h for type 1 MI and after 72 h for type 5 MI. In type 1 MI there
      were additional smaller peaks at 1 h and at 24 h. After successful reperfusion of
      an acute MI there was a second peak at 24 h. There was not enough data available
      to analyze the Tn release after MI associated with percutaneous coronary
      intervention (type 4). CONCLUSION: The typical rise and fall of Tn is different
      for type 1 MI, successful reperfusion of an acute MI and type 5 MI, with
      different timing of the peak levels and different slopes of the fall phase.

PMID- 27022462
TI  - Pharmacologic immunosuppression of mononuclear phagocyte phagocytosis by
      caffeine.
AB  - Caffeine is the most widely used neurostimulant in the world. There is
      considerable debate on its effect on immune cells as it has been shown to
      antagonize adenosine receptors (ARs), which mediate an anti-inflammatory switch
      in activated immune cells. A second target is phosphodiesterase, where it acts as
      an inhibitor. If the primary effect of caffeine on mononuclear phagocytes were to
      antagonize ARs we would expect cells exposed to caffeine to have a prolonged
      proinflammatory response. The aim of this study was to investigate the effects
      and mechanism of action of caffeine in mononuclear phagocytes. Human mononuclear
      phagocytes were separated from whole blood and pretreated with protein kinase A
      inhibitor (PKA) and then exposed to micromolar physiological concentrations of
      caffeine. Phagocytosis and phagocytosis exhaustion were quantified using flow
      cytometry. Treatments were analyzed and compared to controls, using a beta
      regression controlling for factors of age, gender, caffeine intake, and exercise.
      We found that caffeine suppresses phagocytosis at micromolar physiological
      concentrations. This suppression was prevented when mononuclear phagocytes were
      pretreated with PKA inhibitor, suggesting that caffeine's phagocytic suppression
      may be due to its function as a phosphodiesterase inhibitor, pushing cells
      towards an anti-inflammatory response. Additionally, these effects are altered by
      regular caffeine intake and fitness level, emphasizing that tolerance and immune
      robustness are important factors in mononuclear phagocyte activation. These
      results demonstrate that caffeine may be acting as a phosphodiesterase inhibitor
      and suppressing phagocytosis in mononuclear phagocytes by promoting an anti
      inflammatory response. 

PMID- 27022463
TI  - Clearance of rapid adenosine release is regulated by nucleoside transporters and
      metabolism.
AB  - Adenosine is a neuromodulator that regulates neurotransmission in the brain and
      central nervous system. Recently, spontaneous adenosine release that is cleared
      in 3-4 sec was discovered in mouse spinal cord slices and anesthetized rat
      brains. Here, we examined the clearance of spontaneous adenosine in the rat
      caudate-putamen and exogenously applied adenosine in caudate brain slices. The V
      max for clearance of exogenously applied adenosine in brain slices was 1.4 +/-
      0.1 MUmol/L/sec. In vivo, the equilibrative nucleoside transport 1 (ENT1)
      inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI) (1 mg/kg, i.p.) significantly
      increased the duration of adenosine, while the ENT1/2 inhibitor, dipyridamole (10
      mg/kg, i.p.), did not affect duration. 5-(3-Bromophenyl)-7-[6-(4-morpholinyl)-3
      pyrido[2,3-d]byrimidin-4-amine dihydrochloride (ABT-702), an adenosine kinase
      inhibitor (5 mg/kg, i.p.), increased the duration of spontaneous adenosine
      release. The adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine
      (EHNA) (10 mg/kg, i.p.), also increased the duration in vivo. Similarly, NBTI (10
      MUmol/L), ABT-702 (100 nmol/L), or EHNA (20 MUmol/L) also decreased the clearance
      rate of exogenously applied adenosine in brain slices. The increases in duration
      for blocking ENT1, adenosine kinase, or adenosine deaminase individually were
      similar, about 0.4 sec in vivo; thus, the removal of adenosine on a rapid time
      scale occurs through three mechanisms that have comparable effects. A cocktail of
      ABT-702, NBTI, and EHNA significantly increased the duration by 0.7 sec, so the
      mechanisms are not additive and there may be additional mechanisms clearing
      adenosine on a rapid time scale. The presence of multiple mechanisms for
      adenosine clearance on a time scale of seconds demonstrates that adenosine is
      tightly regulated in the extracellular space. 

PMID- 27022464
TI  - Chronic P-glycoprotein inhibition increases the brain concentration of
      escitalopram: potential implications for treating depression.
AB  - Recent preclinical studies have revealed a functionally important role for the
      drug efflux pump P-glycoprotein (P-gp) at the blood-brain barrier in limiting
      brain levels and thus antidepressant-like activity of certain antidepressant
      drugs. Specifically, acute administration of P-gp inhibitors, such as verapamil
      and cyclosporin A (CsA), has been shown to augment brain concentrations and
      functional activity of the antidepressant escitalopram in rodents. However,
      depression is a chronic disorder and current treatments require prolonged
      administration to elicit their full therapeutic effect. Thus, it is important to
      investigate whether acute findings in relation to P-gp inhibition translate to
      chronic paradigms. To this end, the present study investigates whether chronic
      treatment with the P-gp inhibitor verapamil and the antidepressant escitalopram
      results in enhanced brain distribution and antidepressant-like effects of
      escitalopram. Verapamil (10 mg.kg(-1) i.p.) and escitalopram (0.1 mg.kg(-1) i.p.)
      were administered once daily for 22 days. On the final day of treatment, brain
      regions and plasma were collected for analysis of cortical and plasma
      escitalopram concentrations, and to determine the hippocampal expression of genes
      previously reported to be altered by chronic antidepressant treatment. Verapamil
      treatment resulted in a greater than twofold increase in brain levels of
      escitalopram, without altering plasma levels. Neither gene expression analysis
      nor behavioral testing revealed an augmentation of responses to escitalopram
      treatment due to verapamil administration. Taken together, these data demonstrate
      for the first time that P-gp inhibition can yield elevated brain concentrations
      of an antidepressant after chronic treatment. The functional relevance of these
      increased brain levels requires further elaboration.

PMID- 27022465
TI  - Activation of transient receptor potential ankyrin 1 induces CGRP release from
      spinal cord synaptosomes.
AB  - Transient receptor potential ankyrin 1 (TRPA1) is a sensor of nociceptive
      stimuli, expressed predominantly in a subpopulation of peptidergic sensory
      neurons which co-express the noxious heat-sensor transient receptor potential
      vanilloid 1. In this study, we describe a spinal cord synaptosome-calcitonin gene
      related peptide (CGRP) release assay for examining activation of TRPA1 natively
      expressed on the central terminals of dorsal root ganglion neurons. We have shown
      for the first time that activation of TRPA1 channels expressed on spinal cord
      synaptosomes by a selection of agonists evokes a concentration-dependent release
      of CGRP which is inhibited by TRPA1 antagonists. In addition, our results
      demonstrate that depolarization of spinal cord synaptosomes by a high
      concentration of KCl induces CGRP release via a T-type calcium channel-dependent
      mechanism whilst TRPA1-induced CGRP release functions independently of voltage
      gated calcium channel activation. Finally, we have shown that pre-treatment of
      synaptosomes with the opioid agonist, morphine, results in a reduction of
      depolarization-induced CGRP release. This study has demonstrated the use of a
      dorsal spinal cord homogenate assay for investigation of natively expressed TRPA1
      channels and for modulation of depolarizing stimuli at the level of the dorsal
      spinal cord. 

PMID- 27022466
TI  - miRNA-27b levels are associated with CYP3A activity in vitro and in vivo.
AB  - Previous in vitro studies have shown that microRNA-27b (miR-27b) may regulate
      mRNA levels of CYP3A4, vitamin D receptor (VDR), and Peroxisome proliferator
      activated receptor alpha (PPAR alpha) as well as CYP3A4 protein expression and
      activity. In vitro studies have also shown that vitamin D may affect the
      expression of CYP3A4. The primary aim of this pilot study was to investigate the
      association between miR-27b and CYP3A expression and activity. The secondary aim
      was to investigate the association between 25-hydroxy vitamin D in serum and
      CYP3A activity. Mi-RNA-27b was quantified using real-time PCR in serum samples (n
      = 28) and 25-hydroxyvitamin D was measured and correlated with the levels of the
      endogenous CYP3A activity marker 4beta-hydroxycholesterol. In addition, the
      correlation between miR-27b and CYP3A activity, measured by dextromethorphan N
      demethylation and 6beta-hydroxylation of testosterone and the gene expression of
      CYP3A4, VDR and PPAR alpha were assessed in 20 human liver samples. A significant
      association between circulatory miR-27b levels and 4beta-hydroxycholesterol ratio
      was found; P = 0.04, and between hepatic miR-27b levels and CYP3A activity,
      measured by dextromethorphan N-demethylation in human liver (P = 0.04). There was
      no association between hepatic miR-27b and mRNA levels of CYP3A4, VDR or PPAR
      alpha. There was a significant association between serum 25-hydroxyvitamin D
      levels and 4beta-hydroxycholesterol ratio, P = 0.002. In conclusion, this pilot
      study supports the hypothesis that miR-27b levels as well as 25-hydroxyvitamin D
      may affect CYP3A activity in vivo. The results indicate that miR-27b exerts its
      inhibitory effect on a translational level rather than affecting mRNA levels.

PMID- 27022467
TI  - Potential mechanism of enhanced postprandial glucagon-like peptide-1 release
      following treatment with a diacylglycerol acyltransferase 1 inhibitor.
AB  - Studies have demonstrated that blockade of diacylglycerol acyltransferase 1
      (DGAT1) leads to prolonged release of glucagon-like peptide 1 (GLP-1) after meal
      challenge. The current study was undertaken to investigate the mechanism of
      action underlying the elevated levels of GLP-1 release following pharmacological
      inhibition of DGAT1. We utilized a potent, specific DGAT1 inhibitor, compound A,
      to investigate the changes in intestinal lipid profile in a mouse model after
      oral administration of the compound and challenge with tracer containing fatty
      meal. [13C18]-oleic acid and LC-MS were employed to trace the fate of dietary
      fatty acids provided as part of a meal challenge in lean mice. Lipid profiles in
      plasma, proximal to distal segments of intestine, and feces were evaluated at
      various times following the meal challenge to study the kinetics of fatty acid
      absorption, synthesis into complex lipids, and excretion. Pharmacological
      inhibition of DGAT1 led to reduction of postprandial total and newly synthesized
      triglyceride (TG) excursion and significant increases in TG and FFA levels in the
      distal portion of intestine enriched with enteroendocrine L cells. Enhanced
      levels of FFA and cholesteryl ester were observed via fecal fat profiling. DGAT1
      inhibition leads to enhancement of carbon flow to the synthesis of
      phosphatidylcholine within the intestine. DGAT1 inhibition markedly increases
      levels of TG and FFA in the distal intestine, which could be the predominant
      contributor to the prolonged and enhanced postprandial GLP-1 release.
      Inactivation of DGAT1 could provide potential benefit in the treatment of
      dysmetabolic diseases.

PMID- 27022468
TI  - Inhaled loxapine and intramuscular lorazepam in healthy volunteers: a randomized
      placebo-controlled drug-drug interaction study.
AB  - Pharmacodynamic effects and safety of single-dose inhaled loxapine administered
      via the Staccato((r)) system and intramuscular (IM) lorazepam in combination
      versus each agent alone were compared in a randomized, double-blind, crossover
      study in healthy volunteers. Subjects received: inhaled loxapine 10 mg + IM
      lorazepam 1 mg; inhaled loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato
      placebo in random order, each separated by a 3-day washout. Primary endpoints
      were maximum effect (minimum value) and area under the curve (AUC) from baseline
      to 2 h post treatment for respirations/min and pulse oximetry. Least-squares
      means (90% confidence interval [CI]) for concomitant treatment versus each agent
      alone were derived and equivalence (no difference) confirmed if the 90% CI was
      within 0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual
      analog scale), and adverse events (AEs) were recorded. All 18 subjects (mean age,
      20.4 years; 61% male) completed the study. There was no difference between
      inhaled loxapine + IM lorazepam and either agent alone on respiration or pulse
      oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min
      ratios. BP and HR were no different for inhaled loxapine + IM lorazepam and each
      agent alone over a 12-h postdose period. Although the central nervous system
      sedative effects were observed for each treatment in healthy volunteers, the
      effect was greater following concomitant lorazepam 1 mg IM + inhaled loxapine 10
      mg administration. There were no deaths, serious AEs, premature discontinuations
      due to AEs, or treatment-related AEs. 

PMID- 27022469
TI  - Claudin-4 binder C-CPE 194 enhances effects of anticancer agents on pancreatic
      cancer cell lines via a MAPK pathway.
AB  - The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) modulates
      the tight junction protein claudin and disrupts the tight junctional barrier. It
      also can enhance the effectiveness of anticancer agents. However, the detailed
      mechanisms of the effects of C-CPE remain unclear in both normal and cancerous
      cells. The C-CPE mutant called C-CPE 194 binds only to claudin-4, but the C-CPE
      194 mutant called C-CPE m19 binds not only to claudin-4 but also to claudin-1. In
      the present study, to investigate the mechanisms of the effects of C-CPE on
      claudin expression, the tight junctional functions and the cytotoxicity of
      anticancer agents, human pancreatic cancer cells, and normal human pancreatic
      duct epithelial cells (HPDEs) were treated with C-CPE 194 and C-CPE m19. In well
      differentiated cells of the pancreatic cancer cell line HPAC, C-CPE 194 and C-CPE
      m19 disrupted both the barrier and fence functions without changes in expression
      of claudin-1 and -4, together with an increase of MAPK phosphorylation. C-CPE
      194, but not C-CPE m19, enhanced the cytotoxicity of the anticancer agents
      gemcitabine and S-1. In poorly differentiated pancreatic cancer cell line PANC-1,
      C-CPE 194, but not C-CPE m19, decreased claudin-4 expression and enhanced MAPK
      activity and the cytotoxicity of the anticancer agents. In normal HPDEs, C-CPE
      194 and C-CPE m19 decreased claudin-4 expression and enhanced the MAPK activity,
      whereas they did not affect the cytotoxicity of the anticancer agents. Our
      findings suggest that the claudin-4 binder C-CPE 194 enhances effects of
      anticancer agents on pancreatic cancer cell lines via a MAPK pathway.

PMID- 27022470
TI  - Preclinical pharmacology and pharmacokinetics of CERC-301, a GluN2B-selective N
      methyl-D-aspartate receptor antagonist.
AB  - The preclinical pharmacodynamic and pharmacokinetic properties of 4-methylbenzyl
      (3S, 4R)-3-fluoro-4-[(Pyrimidin-2-ylamino) methyl] piperidine-1-carboxylate (CERC
      301), an orally bioavailable selective N-methyl-D-aspartate (NMDA) receptor
      subunit 2B (GluN2B) antagonist, were characterized to develop a translational
      approach based on receptor occupancy (RO) to guide CERC-301 dose selection in
      clinical trials of major depressive disorder. CERC-301 demonstrated high-binding
      affinity (K i, 8.1 nmol L(-1)) specific to GluN2B with an IC 50 of 3.6 nmol L(-1)
      and no off-target activity. CERC-301 efficacy was demonstrated in the forced swim
      test with an efficacy dose (ED 50) of 0.3-0.7 mg kg(-1) (RO, 30-50%); increase in
      locomotor activity was observed at ED 50 of 2 mg kg(-1), corresponding to an RO
      of 75%. The predicted 50% RO concentration (Occ50) in humans was 400 nmol L(-1),
      similar to that predicted for rat, dog, and monkey (300, 200, and 400 nmol L(-1),
      respectively). Safety pharmacology and neurotoxicity studies raised no specific
      safety concerns. A first-in-human study in healthy males demonstrated a dose
      proportional pharmacokinetic profile, with T max of ~1 h and t 1/2 of 12-17 h.
      Based on the preclinical and pharmacodynamic data, doses of >=8 mg in humans are
      hypothesized to have an acceptable safety profile and result in clinically
      relevant peak plasma exposure.

PMID- 27022471
TI  - Translational value of mechanical and vasomotor properties of mouse isolated
      mesenteric resistance-sized arteries.
AB  - Mice are increasingly used in vascular research for studying perturbations and
      responses to vasoactive agents in small artery preparations. Historically, small
      artery function has preferably been studied in rat isolated mesenteric resistance
      sized arteries (MRA) using the wire myograph technique. Although different mouse
      arteries have been studied using the wire myograph no establishment of optimal
      settings has yet been performed. Therefore, the purposes of this study were
      firstly to establish the optimal settings for wire myograph studies of mouse MRA
      and compare them to those of rat MRA. Second, by surveying the literature, we
      aimed to evaluate the overall translatability of observed pharmacological
      vasomotor responses of mouse MRA to those obtained in rat MRA as well as
      corresponding and different arteries in terms of vessel size and species origin.
      Our results showed that the optimal conditions for maximal active force
      development in mouse MRA were not significantly different to those determined in
      rat MRA. Furthermore, we found that the observed concentration-dependent
      vasomotor responses of mouse MRA to noradrenaline, phenylephrine, angiotensin II,
      sarafotoxin 6c, 5-hydroxytryptamine, carbachol, sodium nitroprusside, and
      retigabine were generally similar to those described in rat MRA as well as
      arteries of different sizes and species origin. In summary, the results of this
      study provide a framework for evidence-based optimization of the isometric wire
      myograph setup to mouse MRA. Additionally, in terms of translational value, our
      study suggests that mouse MRA can be applied as a useful model for studying
      vascular reactivity. 

PMID- 27022472
TI  - Modeling the pharmacokinetic-pharmacodynamic relationship of the monoclonal anti
      macaque-IL-15 antibody Hu714MuXHu in cynomolgus monkeys.
AB  - Hu714MuXHu is a recombinant chimeric murine-human monoclonal antibody directed
      against interleukin-15 (IL-15), a proinflammatory cytokine associated with memory
      CD8+ and natural killer (NK) T-cell activation and implicated in the pathogenesis
      of inflammatory diseases. A pharmacokinetic-pharmacodynamic (PK/PD) model was
      developed to describe the NK cell count reduction in cynomolgus monkeys after
      treatment with Hu714MuXHu. Cynomolgus monkeys were dosed with Hu714MuXHu in three
      studies: as a single dose at 0.1 or 1 mg.kg(-1) i.v.; weekly for 5 weeks at 0,
      30, 60, or 150 mg.kg(-1) i.v. or 150 mg.kg(-1) s.c.; weekly for 13 weeks at 0, 5,
      30, or 150 mg.kg(-1) s.c. Serum Hu714MuXHu concentration-time data were analyzed
      using noncompartmental analysis and the PK/NK cell count relationship was
      assessed via simultaneous PK/PD modeling. Hu714MuXHu PK was approximately dose
      proportional between 0.1-150 mg.kg(-1) for i.v. and 5-150 mg.kg(-1) for s.c.
      administration with an elimination half-life of 12.7-18 days. Hu714MuXHu
      administration resulted in rapid and marked reductions in NK cell counts after
      the first dose which recovered fully after the serum Hu714MuXHu concentrations
      approached 0.1 MUg.mL(-1) (assay limit of quantification). PK/PD modeled
      Hu714MuXHu effects on NK cells had an EC 50 of 0.09 MUg.mL(-1). In summary,
      weekly i.v. or s.c. doses with Hu714MuXHu for up to 3 months in cynomolgus
      monkeys demonstrated linear PK and significant NK cell count reduction, which was
      described using PK/PD modeling. This approach may be used to guide investigative
      product dose selections for inflammatory diseases where NK cell count alterations
      are quantifiable. 

PMID- 27022473
TI  - Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets
      compared with coadministration of the individual tablets to healthy subjects.
AB  - Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet
      and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
      The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed-dose
      combination (FDC) tablets compared with coadministration of the individual
      tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs
      were evaluated in this open-label, randomized, single-dose crossover study.
      Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg
      fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg +
      dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2).
      Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were
      obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus
      individual components was concluded if the 90% CIs for FDC to individual
      component geometric mean ratios of C max, AUC 0-T, and AUC inf of both analytes
      were between 0.80 and 1.25. Seventy-two subjects were randomized; 71 (98.6%)
      completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets
      were bioequivalent to the individual tablets administered concomitantly. Food had
      no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic
      exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to
      coadministration of the individual components in healthy subjects under fasted
      conditions and food had no clinically meaningful effect on bioavailability. 

PMID- 27022474
TI  - Inactivation of bacteria from contaminated streams in Limpopo, South Africa by
      silver- or copper-nanoparticle paper filters.
AB  - There is an urgent need for inexpensive point-of-use methods to purify drinking
      water in developing countries to reduce the incidence of illnesses caused by
      waterborne pathogens. Previously, our work showed the deactivation of laboratory
      cultured bacteria by percolation through a thick paper sheet containing either
      silver (Ag) or copper (Cu) nanoparticles (NP). In this study, these paper filters
      containing AgNPs or CuNPs have been tested with water sourced from contaminated
      streams in Limpopo, South Africa. Following the percolation of the contaminated
      stream water through the metal nanoparticle (MNP) papers, the water quality of
      the filtered effluent was evaluated with respect to the colony counts of total
      coliform and E. coli bacteria, turbidity, and either silver or copper ions.
      Influent total coliform bacteria concentrations from the stream water in Limpopo
      ranged from 250 CFU/100 mL to 1,750,000 CFU/100 mL. With the less contaminated
      stream water (250 - 15,000 CFU/100 mL), both AgNP and CuNP papers showed complete
      inactivation of the coliform bacteria. With the surface water with higher
      coliform bacteria levels (500,000 - 1,000,000 CFU/100 mL), both the AgNP and CuNP
      papers showed similar results with a slightly higher bacteria reduction of log10
      5.1 for the AgNP papers than the log10 4.8 reduction for the CuNP papers. E. coli
      results followed similar trends. For most water purification experiments, the
      metal release from the sheets was minimal, with values under 0.1 ppm for Ag and
      1.0 ppm for Cu (the current US EPA and WHO drinking water limits for Ag and Cu,
      respectively). These results show good potential for the use of paper embedded
      with silver and/or copper nanoparticles as effective point-of-use water
      purifiers.

PMID- 27022475
TI  - Gabapentin for uremic pruritus in hemodialysis patients: a qualitative systematic
      review.
AB  - PURPOSE OF THE REVIEW: Uremic pruritus (UP) is a common discomfort of dialysis
      dependent end-stage renal disease. Some studies suggest a neuropathic cause of
      UP. Gabapentin, an anticonvulsant, has shown promising results as an emerging
      drug to treat this condition. OBJECTIVE: An updated qualitative systematic review
      was conducted to evaluate its efficacy and safety in hemodialysis patients.
      SOURCE OF INFORMATION: Ovid MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials, Clinicaltrials.gov, and Google Scholar through June 2015 were
      used as sources of information. PATIENTS: Patients are adult hemodialysis
      patients receiving gabapentin for UP. METHODS: All randomized controlled trials
      (RCTs), quasi-RCTs, observational studies, open-label studies, and retrospective
      studies were included. Case series and case reports were excluded. All
      descriptions and data were extracted independently by two authors. RESULTS: Seven
      studies evaluating gabapentin with a total of 179 patients were included. Most
      patients were refractory to antihistamines and topical emollients. Statistically
      significant favorable outcomes on pruritus scores were found in six studies. Five
      studies evaluated antipruritic efficacy based on a 10-point visual analog scale
      (VAS), and improvements in the range of an absolute decrease of 5.7 to 9.4 points
      from baseline were achieved on average by 3-8 weeks of treatment. Side effects
      are common with six studies reporting at least 26 incidences of side effects such
      as somnolence, dizziness, and fatigue. A total of four patients reportedly
      discontinued gabapentin due to intolerability. LIMITATIONS: Our review is limited
      by the inclusion of generally small, lower quality studies that lacked comparator
      groups or were open-label studies. Since the first two randomized controlled
      trials were published, no further high-quality studies have been conducted.
      IMPLICATIONS: Our review supports a trial of gabapentin for the management of UP
      in hemodialysis patients refractory to antihistamines and/or emollients. The
      results should be interpreted cautiously due to the lower quality of included
      studies. We recommend a starting dose of 100 mg orally after hemodialysis to
      minimize adverse events in this population.

PMID- 27022476
TI  - Exotropia Is the Main Pattern of Childhood Strabismus Surgery in the South of
      China: A Six-Year Clinical Review.
AB  - Purpose. To evaluate the distribution pattern and changes of strabismus surgery
      in children based on the data collected from a local eye hospital in the south of
      China between 2006 and 2011. Methods. A retrospective analysis of all strabismus
      surgeries in children (<18 years) performed in the Eye Hospital of Wenzhou
      Medical University between 2006 and 2011 using the integrated information system.
      Result. A total of 2,219 strabismus surgeries were performed during the study
      period, with concomitant exotropia (44% of all surgeries) more than esotropia
      (27%, chi (2) = 42.7, p < 0.001). Total number of surgeries increased from 250 in
      2006 to 508 in 2011, with a significant increase in concomitant exotropia: 38% of
      all surgeries in 2006 increased to 47% in 2011 (chi (2) = 29.4, p < 0.001). The
      increase of intermittent exotropia was approximately 26% of all increments of
      strabismus surgery between 2006 and 2011. Conclusion. Surgery for childhood
      exotropia was more frequent than esotropia in China. The proportion of exotropia
      progressively increased, while the proportion of esotropia decreased during these
      years. Intermittent exotropia was the main increment of strabismus surgery.
      Further population-based studies are needed to confirm the proportion of surgery
      and whether the incidence of strabismus surgery increased in China. 

PMID- 27022477
TI  - Radial Retinotomies with Endodiathermy for Severe Proliferative
      Vitreoretinopathy: Short-Term Results.
AB  - Purpose. Retinal redetachment of silicone oil-filled eyes continues to be a
      frustrating condition that typically requires retinectomy. We proposed radial
      retinotomy as a potentially less invasive surgery. Here, we preliminarily
      explored its feasibility, efficacy, and safety. Methods. Totally 9 eyes of 9
      consecutive patients were included in a prospective noncomparative trial. A
      series of retinotomies were created by endodiathermy in a radial pattern to relax
      the foreshortened retina. The eye was refilled with fresh silicone oil. The
      treated eyes were examined via visual acuity (VA) tests, tonometry, slit-lamp
      microscopy, and fundus photography during a 6-month observation period. Results.
      The procedure was completed in an average of 28 minutes from silicone oil removal
      to fresh silicone oil placement. Fundus photography demonstrated that 7 of the 9
      eyes (78%) exhibited retinal reattachment. On average, VA was significantly
      improved within the first 2 weeks (P = 0.02) and remained stable for the
      following 6 months. The change in intraocular pressure was not significant (P =
      0.76), and no adverse event was observed (0%). Conclusion. Radial retinotomies
      with endodiathermy were shown to be feasible, effective, and safe in selected
      cases of inferior contracted retina without vitreous base fibrosis over a 6-month
      observation period. This trial is registered with NCT02201706. 

PMID- 27022478
TI  - Clinical Outcomes after Uncomplicated Cataract Surgery with Implantation of the
      Tecnis Toric Intraocular Lens.
AB  - Purpose. To evaluate the clinical outcomes after uncomplicated cataract surgery
      with implantation of an aspheric toric intraocular lens (IOL) during a 6-month
      follow-up. Methods. Prospective study including 27 consecutive eyes of 18
      patients (mean age: 66.1 +/- 11.4 years) with a visually significant cataract and
      corneal astigmatism >= 0.75 D and undergoing uncomplicated cataract surgery with
      implantation of the Tecnis ZCT toric IOL (Abbott Medical Optics). Visual,
      refractive, and keratometric outcomes as well as IOL rotation were evaluated
      during a 6-month follow-up. At the end of the follow-up, patient satisfaction and
      perception of optical/visual disturbances were also evaluated using a subjective
      questionnaire. Results. At 6 months after surgery, mean LogMAR uncorrected (UDVA)
      and corrected distance visual acuity (CDVA) were 0.19 +/- 0.12 and 0.14 +/- 0.10,
      respectively. Postoperative UDVA of 20/40 or better was achieved in 92.6% of
      eyes. Mean refractive cylinder decreased significantly from -3.73 +/- 1.96 to 
      1.42 +/- 0.88 D (p < 0.001), while keratometric cylinder did not change
      significantly (p = 0.44). Mean absolute IOL rotation was 1.1 +/- 2.4 degrees ,
      with values of more than 5 degrees  in only 2 eyes (6.9%). Mean patient
      satisfaction score was 9.70 +/- 0.46, using a scale from 0 (not at all satisfied)
      to 10 (very satisfied). No postoperative optical/visual disturbances were
      reported. Conclusion. Cataract surgery with implantation of the Tecnis toric IOL
      is an effective method of refractive correction in eyes with corneal astigmatism
      due to the good IOL positional stability, providing high levels of patient's
      satisfaction. 

PMID- 27022479
TI  - Efficacy and Safety in Retinal Vein Occlusion Treated with at Least Three
      Consecutive Intravitreal Dexamethasone Implants.
AB  - Purpose. To evaluate the effects of repeated intravitreal dexamethasone implant
      (DI) (Ozurdex(r)) in eyes with macular edema (ME) due to retinal vein occlusion
      (RVO). Methods. Multicenter observational study including patients who received
      more than three consecutive DI on an "as-needed" basis for the treatment of ME in
      RVO. Results. A total of 18 eyes were included for analysis. Mean interval of
      retreatment with DI was 5.1 months between the first and second DI and 5.4 months
      following the second DI. Baseline BCVA was 0.74 +/- 0.08 log-Mar; it
      significantly improved to 0.45 +/- 0.04 2 months after the 3rd DI. There was no
      significant difference between the 3 first postinjection BCVA. CMT decreased from
      617 MUm +/- 120 MUm (baseline) to 330 +/- 109 MUm two months after the third DI.
      Elevated intraocular pressure occurred in 50% and was controlled medically.
      Cataract progression leading to cataract surgery occurred in 69% of phakic eyes
      after a mean interval of 17 months. Conclusion. Repeated DI on an "as-needed"
      basis, with a retreatment interval <6 months, are effective in the long term in
      the management of ME due to RVO. Rates of increased intraocular pressure and
      cataract surgery seem to be higher than previously described when eyes were
      followed during a longer period. 

PMID- 27022480
TI  - Use of Cognitive Interviews to Adapt PROMIS Measurement Items for Spanish
      Speakers Living with HIV.
AB  - Purpose. To use cognitive interviewing techniques to assess comprehension of
      existing Patient-Reported Outcomes Measurement Information System (PROMIS) items
      among Latinos living with HIV and then refine items based on participant
      feedback. Methods. Latino monolingual Spanish speakers living with HIV (n = 56)
      participated in cognitive interviews. Items from four PROMIS domains, including
      depression, anxiety, fatigue, and alcohol use, were assessed for comprehension.
      Audiotaped interviews and handwritten notes were subjected to content analysis to
      identify problems specific to each instrument for each domain. Results. The
      assessments from the cognitive interviews identified areas for improvement in
      each domain. We present data on the type of items that were difficult to
      comprehend and provide examples for how items were refined based on participants'
      and PROMIS Statistical Coordinating Center (PSCC) feedback. Six out of 48
      depression items, 7 out of the 61 anxiety items, 18 out of 42 fatigue items, and
      7 out of 44 alcohol use items were found to have poor comprehension. These items
      were refined based on participant feedback; the items were then submitted to the
      PSCC for additional guidance on linguistics and grammar to improve comprehension.
      Conclusions. Cognitive interviews may be used to enhance comprehension of PROMIS
      items among Latinos. 

PMID- 27022481
TI  - Prevalence of Anemia and Its Associated Factors among Pregnant Women Attending
      Antenatal Care in Health Institutions of Arba Minch Town, Gamo Gofa Zone,
      Ethiopia: A Cross-Sectional Study.
AB  - Background. Anemia during pregnancy is a major cause of morbidity and mortality
      of pregnant women in developing countries and has both maternal and fetal
      consequences. Despite its known serious effect on health, there is very little
      research based evidence on this vital public health problem in Gamo Gofa zone in
      general and in Arba Minch town of Southern Ethiopia in particular. Therefore,
      this study aims to assess the prevalence and factors associated with anemia among
      pregnant women attending antenatal care in health institutions of Arba Minch
      town, Gamo Gofa zone, Southern Ethiopia. Method. Institution-based, cross
      sectional study was conducted from February 16 to April 8, 2015, among 332
      pregnant women who attended antenatal care at government health institutions of
      Arba Minch town. Interviewer-administered questionnaire supplemented by
      laboratory tests was used to obtain the data. Bivariate and multivariate logistic
      regressions were used to identify predictors of anemia. Result. The prevalence of
      anemia among antenatal care attendant pregnant women of Arba Minch town was
      32.8%. Low average monthly income of the family (AOR = 4.0; 95% CI: 5.62-11.01),
      having birth interval less than two years (AOR = 3.1; 95% CI: 6.01, 10.23), iron
      supplementation (AOR = 2.31; 95% CI: 7.21, 9.31), and family size >2 (AOR = 2.8;
      95% CI: 1.17, 6.81) were found to be independent predictors of anemia in
      pregnancy. Conclusion. Anemia is found to be a moderate public health problem in
      the study area. Low average monthly income, birth interval less than two years,
      iron supplementation, and large family size were found to be risk factors for
      anemia in pregnancy. Awareness creation towards birth spacing, nutritional
      counselling on consumption of iron-rich foods, and iron supplementation are
      recommended to prevent anemia among pregnant women with special emphasis on those
      having low income and large family size. 

PMID- 27022482
TI  - A Comparative Study in Learning Curves of Two Different Intracorporeal Knot Tying
      Techniques.
AB  - Objectives. In our study we are aiming to analyse the learning curves in our
      surgical trainees by using two standard methods of intracorporeal knot tying.
      Material and Method. Two randomized groups of trainees are trained with two
      different intracorporeal knot tying techniques (loop and winding) by single
      surgeon for eight sessions. In each session participants were allowed to make as
      many numbers of knots in thirty minutes. The duration for each set of knots and
      the number of knots for each session were calculated. At the end each session,
      participants were asked about their frustration level, difficulty in making knot,
      and dexterity. Results. In winding method the number of knots tied was increasing
      significantly in each session with less frustration and less difficulty level.
      Discussion. The suturing and knotting skill improved in every session in both
      groups. But group B (winding method) trainees made significantly higher number of
      knots and they took less time for each set of knots than group A (loop method).
      Although both knotting methods are standard methods, the learning curve is better
      in loop method. Conclusion. The winding method of knotting is simpler and easier
      to perform, especially for the surgeons who have limited laparoscopic experience.

PMID- 27022483
TI  - Health Seeking Behaviour and Associated Factors among Pulmonary Tuberculosis
      Suspects in Lay Armachiho District, Northwest Ethiopia: A Community-Based Study.
AB  - Studies in the northern part of Ethiopia showed high prevalence of undiagnosed
      cluster of tuberculosis cases within the community which demanded an
      investigation of the health care seeking behaviour of tuberculosis suspects. A
      community-based cross-sectional study was conducted in Lay Armachiho district,
      Northwest Ethiopia. Individuals who had cough for at least two weeks and aged
      greater than or equal to 15 years were included in the study. Data were collected
      by interview using pretested and structured questionnaire. Logistic regression
      was computed and adjusted odds ratio with 95% confidence interval was calculated.
      Out of the total population surveyed (29, 735), 663 (2.2%) individuals were found
      to be pulmonary tuberculosis suspects. Majority of the suspects reported that
      they had visited a modern health care facility. Those aged 15 to 34 and aged 35
      54 had secondary educational level and above; those who were civil servants,
      those who were farmers, those who had previous history of tuberculosis treatment,
      and those who perceived that they were sick were more likely to visit a modern
      health care facility. The proportion of respondents who had taken traditional
      measures was found to be higher than some other districts. Improving the
      socioeconomic status of the community is recommended. 

PMID- 27022484
TI  - Synthesis, In Vivo Anti-Inflammatory Activity, and Molecular Docking Studies of
      New Isatin Derivatives.
AB  - A novel synthesis of 2-hydroxy-N'-(2-oxoindolin-3-ylidene) benzohydrazide
      derivatives was synthesized by the condensation of 2-hydroxybenzohydrazide with
      substituted isatins. The synthesized compounds were characterized by FT-IR, (1)H
      NMR, and mass spectral data. Further, the compounds were screened for in vivo
      anti-inflammatory activity by carrageenan induced paw edema method. The tested
      compounds have shown mild-to-moderate anti-inflammatory activity. The compounds
      VIIc and VIId exhibited 65% and 63% of paw edema reduction, respectively. The
      molecular docking studies were also carried out into the active site of COX-1 and
      COX-2 enzymes (PDB ID: 3N8Y, 3LN1, resp.) using VLife MDS 4.3. The compounds
      VIIc, VIId, and VIIf exhibited good docking scores of -57.27, -62.02, and -58.18
      onto the active site of COX-2 and least dock scores of -8.03, -9.17, and -8.94 on
      COX-1 enzymes and were comparable with standard COX-2 inhibitor celecoxib. A
      significant correlation was observed between the in silico and the in vivo
      studies. The anti-inflammatory and docking results highlight the fact that the
      synthesized compounds VIIc, VIId, and VIIf could be considered as possible hit as
      therapeutic agents. 

PMID- 27022485
TI  - Encephalitozoon cuniculi: Grading the Histological Lesions in Brain, Kidney, and
      Liver during Primoinfection Outbreak in Rabbits.
AB  - This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in
      farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited
      clinical signs of this zoonotic emerging disease, like torticollis, ataxia,
      paresis, circling, and rolling. Samples of brain, kidney, and liver were examined
      for histology lesions. For the first time the lesions caused by E. cuniculi were
      graded according to their severity (I, II, and III) and the size of the
      granulomas (Types A, B, and C). The main cerebral injuries were Grade III,
      coinciding with the presence of Type C granulomas. The cerebral lesions were
      located in the cortex, brain stem, and medulla. The renal lesions were also Grade
      III distributed throughout cortex and renal medulla, with no granuloma formation.
      The involvement of hypersensitivity Types III and IV is suggested. All of the
      rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this
      zoonotic and emerging pathogen is widely distributed among animals intended for
      human consumption. We believe this work could be used as a guide when examining
      E. cuniculi and will provide direction to confirm the diagnosis of this pathogen.

PMID- 27022486
TI  - Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine.
AB  - Tremendous technological advancements in prostate radiotherapy have decreased
      treatment toxicity and improved clinical outcomes for men with prostate cancer.
      While these advances have allowed for significant treatment volume reduction and
      whole-organ dose escalation, further improvement in prostate radiotherapy has
      been limited by classic techniques for diagnosis and risk stratification.
      Developments in prostate imaging, image-guided targeted biopsy, next-generation
      gene expression profiling, and targeted molecular therapies now provide
      information to stratify patients and select treatments based on tumor biology.
      Image-guided targeted biopsy improves detection of clinically significant cases
      of prostate cancer and provides important information about the biological
      behavior of intraprostatic lesions which can further guide treatment decisions.
      We review the evolution of prostate magnetic resonance imaging (MRI) and MRI
      ultrasound fusion-guided prostate biopsy. Recent advancements in radiation
      therapy including dose escalation, moderate and extreme hypofractionation,
      partial prostate radiation therapy, and finally dose escalation by simultaneous
      integrated boost are discussed. We also review next-generation sequencing and
      discuss developments in targeted molecular therapies. Last, we review ongoing
      clinical trials and future treatment paradigms that integrate targeted biopsy,
      molecular profiling and therapy, and prostate radiotherapy. 

PMID- 27022487
TI  - Symptomatic Trifascicular Block in Steinert's Disease: Is It Too Soon for a
      Pacemaker?
AB  - We report a case of a 62-year-old male with Steinert's disease who presented with
      progressive intermittent episodes of lightheadedness five years after he was
      diagnosed with the disease. On evaluation, he developed a new onset trifascicular
      block (first degree atrioventricular block, new onset right bundle branch block,
      and left anterior fascicular block). A dual chamber pacemaker was inserted and
      lightheadedness improved significantly. 

PMID- 27022488
TI  - A Rare Case of Renal Infarct due to Noncompaction Cardiomyopathy: A Case Report
      and Literature Review.
AB  - Left ventricular noncompaction cardiomyopathy is a rare myocardial disorder which
      results from failure of left ventricle to compact in embryogenesis. We present a
      case of a 53-year-old female who came because of abdominal pain and was found to
      have renal infarct secondary to noncompaction cardiomyopathy. 

PMID- 27022489
TI  - Histological Features and Biocompatibility of Bone and Soft Tissue Substitutes in
      the Atrophic Alveolar Ridge Reconstruction.
AB  - The reconstruction of the atrophic alveolar ridges for implant placement is today
      a common procedure in dentistry daily practice. The surgical reconstruction
      provides for the optimization of the supporting bone for the implants and a
      restoration of the amount of keratinized gingiva for esthetic and functional
      reasons. In the past, tissue regeneration has been performed with autogenous bone
      and free gingival or connective tissue grafts. Nowadays, bone substitutes and
      specific collagen matrix allow for a complete restoration of the atrophic ridge
      without invasive harvesting procedures. A maxillary reconstruction of an atrophic
      ridge by means of tissue substitutes and its histological features are then
      presented. 

PMID- 27022490
TI  - Vestibular Schwannoma Presenting as Oral Dysgeusia: An Easily Missed Diagnosis.
AB  - We present a case of a fifty-year-old male patient who was referred to the Oral
      Medicine Department with a complaint of a salty taste. History taking
      subsequently revealed that the patient was also experiencing intermittent
      numbness of his left lower lip, tinnitus, and a feeling of fullness in the left
      ear. Magnetic resonance imaging was performed which revealed a large vestibular
      schwannoma affecting the left vestibulocochlear nerve, which was treated
      surgically. This case shows the importance of taking a detailed history in a
      patient presenting with an initial complaint of oral dysgeusia. It also
      highlights the possibility of significant underlying pathology, presenting with
      initial low level, nonspecific complaints such as an altered taste, and the
      rationale for imaging patients who report unilateral facial hypoesthesia. 

PMID- 27022491
TI  - Eleven Primary Melanomas, Colon Cancer, and Atypical Nevi in the Same Patient: A
      Case Report and Literature Review.
AB  - Background. As the incidence of cutaneous malignant melanoma increases in the
      Caucasian population, an increasing population of melanoma survivors is at risk
      of developing multiple primary melanomas (MPM) as well as secondary primary
      cancers. Objective. To present a case of a patient with atypical nevi, 11 primary
      melanomas over 33 years, and colon cancer and to review the literature on
      multiple primary melanomas, atypical nevi, and correlation of nonmelanoma
      cancers. Conclusion. The literature indicates that patients with MPM are not
      uncommon, although 11 primary melanomas are rarely described, that patients with
      MPM may have a better survival than patients with single primary melanoma, that
      atypical nevi are a risk marker of not only melanoma in general but also MPM, and
      that melanoma patients have a significantly increased risk of developing
      nonmelanoma skin and other cancers, which may be even higher for patients with
      MPM. 

PMID- 27022492
TI  - Thyroid Ultrasound Pitfalls: Esophageal Fibrovascular Polyp Mimicking Thyroid
      Nodule.
AB  - Background. Ultrasound (US) is the most accurate tool in the diagnosis of thyroid
      nodules if performed by expert physician. Misdiagnosis due to extrathyroidal
      lesions mimicking thyroid nodules is reported in literature. We describe the
      first case of an esophageal fibrovascular polyp misdiagnosed as a thyroid nodule
      on US examination. Patient Findings. A 54-year-old woman presented to emergency
      department for headache and underwent carotid Doppler extended to neck ultrasound
      with incidental finding of a nodule in the posterior side of the left thyroid
      lobe. A following thyroid US performed by an endocrinologist allowed the
      characterization of the lesion as an esophageal pathology, considering the
      extrathyroidal position, the typical peripheral hyperechoic spots and hypoechoic
      rim, the connection to the esophagus, and the swallowing connected movement. The
      patient was addressed to further investigations and finally to anterior
      pharyngotomy with histological diagnosis of esophageal fibrovascular polyp.
      Summary. Differential diagnosis between thyroid nodules and other neck lesions is
      important to prevent an unnecessary fine needle aspiration biopsy and to treat
      the extrathyroidal pathology. In this case, an US performed by an expert
      endocrinologist allowed detecting an esophageal fibrovascular polyp requiring
      surgical removal. In conclusion, the possibility of an esophageal pathology, and
      even fibrovascular polyp, should be considered during US thyroid examination. 

PMID- 27022493
TI  - Mycetoma Caused by Acremonium Species in a Patient with Chronic Granulomatous
      Disease.
AB  - Patients with chronic granulomatous disease are predisposed to fungal infections
      and are therefore routinely prescribed antifungal prophylaxis. We report a case
      where acremonium was responsible for causing a cutaneous infection (mycetoma)
      despite antifungal prophylaxis. Treatment with voriconazole was initiated and the
      infection gradually resolved. This case highlights the need for careful clinical
      follow-up and thorough investigation of patients who have a neutrophil
      immunodeficiency. 

PMID- 27022494
TI  - Tuberculous Enteritis: A Rare Complication of Miliary Tuberculosis.
AB  - Tuberculous enteritis is a clinical rarity even in immunocompromised patients. We
      present a case of miliary tuberculosis with gastrointestinal involvement. A 47
      year-old homosexual male from Philippines with no significant medical history
      presented with productive cough, night sweats, subjective fevers, shortness of
      breath, watery diarrhea, and 25-pound weight loss in past one year. On physical
      exam he was afebrile, mildly hypotensive, tachycardic, and tachypneic, but
      saturating well on room air. He was cachectic with oral thrush and bilateral fine
      rales. Chest X-ray revealed a miliary pattern. His sputum AFB smear was strongly
      positive. PCR and sputum culture were positive for Mycobacterium tuberculosis. He
      was started on Rifampin, Isoniazid, Ethambutol, and Pyrazinamide. He was found to
      be HIV positive with an absolute CD4 count of 4 cells/MUL. Due to persistent
      diarrhea, stool was sent for AFB culture and grew M. tuberculosis. He responded
      well to treatment with resolution of symptoms. Tuberculous enteritis occurs in
      about 2% of the patients with pulmonary tuberculosis. Although it is uncommon, it
      should be considered in patients with active pulmonary tuberculosis and abdominal
      complaints. A presumptive diagnosis of tuberculous enteritis can be made in the
      setting of active pulmonary tuberculosis with suggestive clinical, endoscopic,
      and/or radiographic findings. 

PMID- 27022495
TI  - Inadvertent Trypan Blue Staining of Posterior Capsule during Cataract Surgery
      Associated with "Argentinian Flag" Event.
AB  - Trypan blue is common in visualizing the anterior capsule during cataract
      surgery. Inadvertent staining of the posterior capsule during phacoemulsification
      is a rare complication and there are few reports in the literature. The proposed
      mechanism of posterior capsule staining in previous reports includes a
      compromised zonular apparatus or iris retractors facilitating the posterior flow
      of trypan blue. We report the first case of trypan blue staining of the posterior
      capsule associated with the "Argentinian flag" sign. In our case, the
      "Argentinian flag" allowed the trypan blue to seep between the posterior capsule
      and the lens, staining the anterior surface of the posterior capsule. 

PMID- 27022496
TI  - Tracheobronchomegaly as a Cause of Bronchiectasis in an Adult.
AB  - Mounier-Kuhn syndrome (MKS) is a rare congenital anomaly characterized by dilated
      trachea and main bronchi due to atrophy of the elastic fibers and smooth muscle
      cells of the trachea and major airways. Patients of MKS can have varied
      presentation. The diagnosis is established radiologically and bronchoscopically.
      There is no specific treatment for MKS. We present an adult man with MKS who
      presented with recurrent respiratory tract infection. The diagnosis was confirmed
      by imaging study and fiberoptic bronchoscopy. 

PMID- 27022497
TI  - Giant Intraperitoneal Multiloculated Pseudocyst in a Male.
AB  - Intraperitoneal pseudocysts are rare and may be difficult to differentiate from
      other malignant neoplasms. Reports of occurrences are mainly associated with long
      term intraperitoneal catheter use, intraperitoneal catheter infections, or major
      pelvic surgery in females, although there are few reported incidences without
      prior trauma. We present a case of a male patient found to have a 19 * 15 * 9 cm
      intraperitoneal pseudocyst with other multiloculated areas and a history of a
      right inguinal hernia repair. After a thorough review of the literature, this is
      the first multiloculated nonpancreatic pseudocyst reported in a male patient. 

PMID- 27022498
TI  - Holmium Laser Enucleation of the Prostate and Iatrogenic Arteriovenous Fistula
      Treated by Superselective Arterial Embolization.
AB  - Iatrogenic pelvic pseudoaneurysm with concomitant arteriovenous fistula has been
      described as a rare and challenging complication, which may occur during
      transurethral resection of the prostate. We provide the first report of this
      complication after holmium laser enucleation of the prostate for the treatment of
      benign prostatic hyperplasia. The attempt to control the bleeding by conversion
      to open surgery and placement of haemostatic stitches into the prostatic fossa
      failed. Angiography with superselective arterial embolization proved to be a
      modern, quick, safe, and efficient treatment of this uncommon complication. 

PMID- 27022499
TI  - Role of Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis and Early
      Treatment of Acute Kidney Injury in a Case Series of Patients with Acute
      Decompensated Heart Failure: A Case Series.
AB  - Patients with acute decompensated heart failure (ADHF) frequently develop
      worsening in renal function until Acute Kidney Injury (AKI). The use of kidney
      injury biomarkers could be useful in the early diagnosis of AKI. In the present
      study, the role of the neutrophil gelatinase-associated lipocalin (NGAL),
      compared to the standard creatinine, in ADHF patients, was analyzed to evaluate
      if an early treatment could affect the outcome. A case series of 24 ADHF patients
      was enrolled and patients randomly divided in two groups (Group A and Group B).
      In Group A, NGAL, creatinine, and eGFR were measured, while in Group B,
      creatinine and eGFR alone were measured. NGAL was measured by turbidimetric
      immunoassay and creatinine using an enzymatic spectrophotometric method. In
      presence of AKI, creatinine increase and eGFR decrease were significantly lower
      in Group A than in Group B, whereas in absence of AKI the difference between the
      two groups was not significant. Hospitalization stay was significantly lower in
      Group A (receiving early treatment based on NGAL) than in Group B. In ADHF
      patients, plasma NGAL in combination with creatinine was superior to the standard
      creatinine in the diagnosis and early treatment of AKI with a better outcome and
      a decreased hospital stay. 

PMID- 27022500
TI  - Impact of Additional Transthoracic Electrical Cardioversion on Cardiac Function
      and Atrial Fibrillation Recurrence in Patients with Persistent Atrial
      Fibrillation Who Underwent Radiofrequency Catheter Ablation.
AB  - Backgrounds and Objective. During the procession of radiofrequency catheter
      ablation (RFCA) in persistent atrial fibrillation (AF), transthoracic electrical
      cardioversion (ECV) is required to terminate AF. The purpose of this study was to
      determine the impact of additional ECV on cardiac function and recurrence of AF.
      Methods and Results. Persistent AF patients received extensive encircling
      pulmonary vein isolation (PVI) and additional line ablation. Patients were
      divided into two groups based on whether they need transthoracic electrical
      cardioversion to terminate AF: electrical cardioversion (ECV group) and
      nonelectrical cardioversion (NECV group). Among 111 subjects, 35 patients were
      returned to sinus rhythm after ablation by ECV (ECV group) and 76 patients had AF
      termination after the ablation processions (NECV group). During the 12-month
      follow-ups, the recurrence ratio of patients was comparable in ECV group (15/35)
      and NECV group (34/76) (44.14% versus 44.74%, P = 0.853). Although left atrial
      diameters (LAD) decreased significantly in both groups, there were no significant
      differences in LAD and left ventricular cardiac function between ECV group and
      NECV group. Conclusions. This study revealed that ECV has no significant impact
      on the maintenance of SR and the recovery of cardiac function. Therefore, ECV
      could be applied safely to recover SR during the procedure of catheter ablation
      of persistent atrial fibrillation. 

PMID- 27022501
TI  - The Possible Role of Mast Cells in the Odontogenic Cyst's Pathogenesis: A
      Comparative Study between Dentigerous Cyst and Keratocystic Odontogenic Tumor.
AB  - Background. Recently, mast cells were recognized in the pathogenesis of more
      aggressive pathologic lesions. This study was aimed to evaluate and compare the
      density of mast cells in Dentigerous cyst (DC) and Keratocystic odontogenic tumor
      (KCOT) regarding their different clinical behavior. Method. This study was
      conducted on 23 and 26 cases of DC and KCOT, respectively. Four-micron sections
      were prepared for Toluidine blue staining and mast cell densities in two desired
      cysts were studied. Final data was analyzed via t-test and Mann-Whitney U test
      method regarding the significant level lower than 0.05. Results. Mast cell
      densities were significantly higher in KCOTs for deep and superficial layers and
      both layers (P < 0.05). The density of degranulated mast cells in the deeper
      layers and both layers was significantly higher in KCOTs (P < 0.05). However, the
      density of degranulated mast cells in the superficial layer had no significant
      difference (P > 0.05). Conclusion. It seems that mast cells may be involved in
      the pathogenesis of KCOT, but, regarding wide range of mast cell's biologic
      activities, further investigations are recommended to confirm the issue and
      prepare the details. 

PMID- 27022502
TI  - Improved Chiral Separation of (R,S)-Goitrin by SFC: An Application in Traditional
      Chinese Medicine.
AB  - Like chemical drugs, research and development of herbal medicine also have a need
      to resolve enantiomers. To help illustrating the antiviral bioactivity of
      Isatidis Radix, a widely used traditional Chinese medicine (TCM), supercritical
      fluid chromatography (SFC) was used for analytical and preparative separation of
      (R,S)-goitrin, which was reported as the active ingredient of the herbal.
      Improved resolution was achieved on Chiralpak IC column, using acetonitrile as
      the organic modifier, representing a tenfold increase in speed, compared to the
      previous normal phase HPLC (NPLC) method. The newly developed chromatographic
      method was validated in terms of linearity, precision, limit of detection (LOD),
      and limit of quantitation (LOQ). Scale-up purification of (R)-goitrin and (S)
      goitrin was performed on a preparative column with >90% total recovery. The
      absolute stereochemical assignment of the purified isomers was determined through
      optical rotation study. This attempt explored SFC's application in chiral
      research of traditional Chinese medicine. 

PMID- 27022503
TI  - Latent and Asymptomatic Toxocara Infection among Young Population in Northwest
      Iran: The Necessity of Informing People as a Potential Health Risk.
AB  - Objectives. This study was designed to determine the frequency of anti-Toxocara
      antibodies in youngsters aging from 2 to 20 years in northwest Iran. Materials
      and Methods. 397 samples were taken randomly almost equally from four locations
      in Urmia, west Azerbaijan, during August 2014 to September 2015. Anti-Toxocara
      IgG antibody assays were done on sera by using ELISA kit (IBL, Germany). In order
      to prevent cross-reaction, the samples of the patients who are infected with
      other parasites in stool exam, especially Ascarididae family, were also excluded.
      SPSS 16.0 software was used for statistical analysis. Results. 12 (3%) of the
      serum samples were positive for anti-Toxocara IgG. According to the Chi-square
      analysis, risk factors such as mother's educational level, keeping dogs or cats
      as pets, and history of coughing were related to Toxocara infection (P < 0.05).
      There was no relationship between toxocariasis and gender, history of
      onychophagy, pica, fever, abdominal pain, and anorexia; however, we found a
      significant relationship between Toxocara infection and chronic coughing (P =
      0.045). Conclusion. Toxocariasis in northwest Iran can be considered as a public
      health problem. This study may also help to increase the awareness about this
      infection. 

PMID- 27022504
TI  - Evaluation of Modified Categorical Data Fuzzy Clustering Algorithm on the
      Wisconsin Breast Cancer Dataset.
AB  - The early diagnosis of breast cancer is an important step in a fight against the
      disease. Machine learning techniques have shown promise in improving our
      understanding of the disease. As medical datasets consist of data points which
      cannot be precisely assigned to a class, fuzzy methods have been useful for
      studying of these datasets. Sometimes breast cancer datasets are described by
      categorical features. Many fuzzy clustering algorithms have been developed for
      categorical datasets. However, in most of these methods Hamming distance is used
      to define the distance between the two categorical feature values. In this paper,
      we use a probabilistic distance measure for the distance computation among a pair
      of categorical feature values. Experiments demonstrate that the distance measure
      performs better than Hamming distance for Wisconsin breast cancer data. 

PMID- 27022505
TI  - Studies on Liquefaction Time and Proteins Involved in the Improvement of Seminal
      Characteristics in Dromedary Camels (Camelus dromedarius).
AB  - Semen was collected from six dromedary camels using artificial vagina during
      rutting season. Liquefaction of the viscous semen occurred in 23.89 +/- 1.49 h.
      During liquefaction, proteins with molecular masses of 24.55 kDa and 22.07 kDa
      appeared in conjunction with the disappearance of intact 26.00 kDa protein after
      18-24 h. These proteins were identified as beta-nerve growth factors (beta-NGFs)
      in liquefied camel semen. Guanidine-HCL improves the rheological characteristics
      of dromedary camel semen along with significant (P < 0.01) increase in sperm
      motility. No significant differences were found in viability of spermatozoa
      indicating no visible detrimental effects on spermatozoa. The cause of semen
      viscosity, as well as proteins that are present in liquefied dromedary camel
      seminal plasma, is described for the first time. 

PMID- 27022506
TI  - Maternal Health-Related Quality of Life and Its Predicting Factors in the
      Postpartum Period in Iran.
AB  - Background/Purpose. Postpartum period is accompanied by many physical, emotional,
      and social changes in women's health. The aim of this study was to examine the
      mothers' quality of life in postpartum period. In addition, it also sought to
      recognize the variables that predict their quality of life. Methods. This cross
      sectional, descriptive study was undertaken among 380 women in 10 urban health
      centers in Ilam province in west of Iran. They were selected using proportional
      random sampling method. The SF-36 questionnaire was used to identify women's
      health-related quality of life (HRQoL). Data were analyzed using SPSS version 15.
      Results. Women who were employed, aged less than 30 years, had college degree,
      have no history of disease in pregnancy, and had given birth more than 3 months
      ago had higher quality of life scores. Independent predictors for lower physical
      HRQoL were being with history of disease in pregnancy; being with high school
      diploma or lower education; and giving birth less than 3 months ago. Also,
      independent predictor for lower mental HRQoL was being housewife. Conclusion.
      According to study findings, greater attention must be paid to providing
      postpartum healthcare for housewife and less educated women as well as those with
      history of disease in pregnancy. 

PMID- 27022507
TI  - Neuroferritinopathy: Pathophysiology, Presentation, Differential Diagnoses and
      Management.
AB  - BACKGROUND: Neuroferritinopathy (NF) is a rare autosomal dominant disease caused
      by mutations in the ferritin light chain 1 (FTL1) gene leading to abnormal
      excessive iron accumulation in the brain, predominantly in the basal ganglia.
      METHODS: A literature search was performed on Pubmed, for English-language
      articles, utilizing the terms iron metabolism, neurodegeneration with brain iron
      accumulation, and NF. The relevant articles were reviewed with a focus on the
      pathophysiology, clinical presentation, differential diagnoses, and management of
      NF. RESULTS: There have been nine reported mutations worldwide in the FTL1 gene
      in 90 patients, the most common mutation being 460InsA. Chorea and dystonia are
      the most common presenting symptoms in NF. There are specific features, which
      appear to depend upon the genetic mutation. We discuss the occurrence of specific
      mutations in various regions along with their associated presenting
      phenomenology. We have compared and contrasted the commonly occurring syndromes
      in the differential diagnosis of NF to guide the clinician. DISCUSSION: NF must
      be considered in patients presenting clinically as a progressive movement
      disorder with variable phenotype and imaging evidence of iron deposition within
      the brain, decreased serum ferritin, and negative genetic testing for other more
      common movement disorders such as Huntington's disease. In the absence of a
      disease-specific treatment, symptomatic drug therapy for specific movement
      disorders may be used, although with variable success.

PMID- 27022508
TI  - Coping Styles in Twins Discordant for Schizophrenia, Bipolar Disorder, and
      Depression.
AB  - Schizophrenia, bipolar disorder, and major depression share several clinical and
      etiological factors. Coping is a critical mediator of the relationship between
      stress and psychopathology and a point of clinical intervention for all three
      disorders. However, little is known about their degree of overlap in coping
      style, or the influence of unique or shared genetic diathesis. In this study, we
      examined five factors of coping within and across disorder proband and co-twin
      groups, modeled heritability, and tested for endophenotypic pattern in a sample
      of twin pairs recruited from the Swedish Twin Registry (N = 420). Although there
      was substantial phenotypic overlap across disorders, including low levels of
      Productive, Problem-Focused coping and high levels of Disengagement, each
      disorder was associated with a unique profile across other dimensions of coping.
      We also found evidence of heritability for three of five factors, yet little
      evidence of genotypic overlap among disorders contributing to similar strategy
      use.

PMID- 27022509
TI  - LIMPING IN CHILDREN.
AB  - Limping in children is a common complaint at pediatric, pediatric orthopaedic
      offices and in emergency rooms. There are several causes for this condition, and
      identifying them is a challenge. The older the patient, the better the anamnesis
      and more detailed the physical examination will be, enabling an easier medical
      assessment for searching the source of the disorder. In order to make the
      approach easier, three age groups can and should be considered. Among infants (1
      to 3 years old), diagnosis will most likely be: transitory synovitis, septic
      arthritis, neurological disorders (mild brain palsy (BP) and muscular dystrophy),
      congenital hip dislocation (CHD), varus thigh, juvenile rheumatoid arthritis
      (JRA) and neoplasias (osteoid osteoma, leukemia); in the scholar age group,
      between 4 and 10 years old, in addition to the diagnoses above, Legg-Calve
      Perthes disease, discoid meniscus, inferior limbs discrepancy and unspecific
      muscular pain; in adolescents (11 to 15 years old): slipped capital femoral
      epiphysis, congenital hip dislocation, chondrolysis, overuse syndromes, dissecans
      osteochondritis, and tarsal coalition. The purpose of this study is to provide an
      update on how to approach pediatric patients presenting with limping, and to
      discuss its potential causes. 

PMID- 27022510
TI  - HOW DO BONE CELLS SENSE MECHANICAL LOADING?
AB  - Influenced by gravidity, bone tissue experiences stronger or lighter deformation
      according to the strength of the activities of daily life. Activities resulting
      in impact are particularly known to stimulate osteogenesis, thus reducing bone
      mass loss. Knowing how bone cells recognize the mechanical deformation imposed to
      the bone and trigger a series of biochemical chain reactions is of crucial
      importance for the development of therapeutic and preventive practices in
      orthopaedic activity. There is still a long way to run until we can understand
      the whole process, but current knowledge has shown a strong progression, with
      researches being conducted focused on therapies. For a mechanical sign to be
      transformed into a biological one (mechanotransduction), it must be amplified at
      cell level by the histological structure of bone tissue, producing tensions in
      cell membrane proteins (integrins) and changing their spatial structure. Such
      change activates bindings between these and the cytoskeleton, producing focal
      adhesions, where cytoplasmatic proteins are recruited to enable easier
      biochemical reactions. Focal adhesion kinase (FAK) is the most important one
      being self-activated when its structure is changed by integrins. Activated FAK
      triggers a cascade of reactions, resulting in the activation of ERK-1/2 and Akt,
      which are proteins that, together with FAK, regulate the production of bone mass.
      Osteocytes are believed to be the mechanosensor cells of the bone and to transmit
      the mechanical deformation to osteoblasts and osteoclasts. Ionic channels and gap
      junctions are considered as intercellular communication means for biochemical
      transmission of a mechanical stimulus. These events occur continuously on bone
      tissue and regulate bone remodeling. 

PMID- 27022511
TI  - RECONSTRUCTION OF THE ANTERIOR CRUCIATE LIGAMENT WITH THE CENTRAL THIRD OF THE
      QUADRICEPS MUSCLE TENDON: ANALYSIS OF 10-YEAR RESULTS.
AB  - OBJECTIVE: Assess clinical results using two different protocols, 10 years after
      ACL reconstruction surgery with the central third of quadriceps muscle tendon
      (QT). METHOD: Between November /1997 and April/1998, 25 patients were submitted
      to 25 ACL reconstructions with QT by transtibial technique. The bone portion of
      the graft was fixated on femoral tunnel with interference screw and the tendinous
      portion of tibial tunnel with screw with washer. Two patients injured the new
      when playing soccer. Six patients were not available for follow-up (24%).
      Seventeen patients were evaluated, 15 men and two women, with mean age at surgery
      time of 28.53 +/- 6.64 years. All patients were examined at six months, one year,
      and ten years after surgery. Clinical evaluation was made by the Lysholm scale,
      and the knee evaluation, with the Hospital for Special Surgery scale. RESULTS:
      The patients had their injuries operated after 9.87 +/- 14.42 months of the
      accident. According to Lysholm scale, the results at the end of the first year
      were 98.71 +/- 2.47 and, after 10 years, 97.35 +/- 3.12. Using the Hospital for
      Special Surgery scale, the mean score was 95.07 +/- 5.23 in one year, and 94.87
      +/- 4.16 in 10 years. All patients returned to their professional activities with
      the same previous status. Fifteen (88.24%) patients were able to return to their
      sports activities, one by modifying the practice, while another one switched to
      another sport. No patient complained of pain on the donor area in the medium and
      long term. The sports return rate was excellent, and no changes were found on the
      femoropatellar joint.

PMID- 27022512
TI  - RADIOLOGICAL ANALYSIS OF EXPERIMENTAL DISC DEGENERATION IN RABBITS.
AB  - OBJECTIVE: To validate radiographic evaluation of a rabbit model for disc
      degeneration. METHODS: Lumbar intervertebral discs of New Zealand rabbits were
      stabbed three times with a 18G needle at a limited depth of 5mm, through lateral
      approach. Serial radiographic images were taken on the early pre-and
      postoperative periods, and after four, eight and 12 weeks of the procedure, with
      subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and
      presence of disc degeneration. The statistical analysis of data was validated by
      the Kappa coefficient, with a confidence interval (CI) of 95%. RESULTS: A
      significant reduction of disc space was found on AP X-ray images after 12
      postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72) with p < 0.001. X
      ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86)
      with p < 0.001. The remaining assessed criteria showed positive results, but with
      a lower Kappa value. CONCLUSION: The disc degeneration model using rabbits as
      proposed in this study was shown to be feasible, with positive X-ray correlation
      between pre- and postoperative images, validating the potential to induce disc
      degeneration in this animal model for future studies.

PMID- 27022513
TI  - ARTHROSCOPIC TREATMENT OF SYNOVIAL OSTEOCHONDROMATOSIS OF THE HIP.
AB  - OBJECTIVE: The objective of this study is to show the results achieved in the
      treatment of hip osteochondromatosis by arthroscopy. METHODS: Six patients
      submitted to hip arthroscopy for synovial osteochondromatosis have been assessed
      for pre- and postoperative function and pain. The time of preoperative complaint
      ranged from nine to 48 months, in an average of 28.2 months and the follow-up
      ranged from eight to 25 months (mean: 17.1 months). Mean age was 45.1 years, with
      four female patients (66.6%) and the right side affected in five cases (83.3%).
      RESULTS: Concerning the results according to Byrd-modified Harris' criteria, the
      mean score evolved from 54.1 to 90.4, and the mean score on the face expressions
      scale for pain assessment ranged from 1.7 to 5.1. CONCLUSION: arthroscopy is a
      good alternative for hip osteochondromatosis treatment, although longer follow-up
      times are required to strictly stating this. The results found so far are
      encouraging, constituting a littleinvasive procedure allowing good recovery.

PMID- 27022514
TI  - COMPARATIVE STUDY BETWEEN TRADITIONAL TENOLYSES AND WITH INTRAOPERATIVE AWAKENING
      PERFORMED ON THE FLEXOR OSTEOFIBROUS TUNNEL REGION OF THE HANDS (ZONE 2).
AB  - OBJECTIVE: Flexor tendon tenolysis on zone 2 is a difficult and really
      challenging for hand surgery. With the objective of comparing the results
      obtained between tenolyses with intraoperative awakening, performed with
      locoregional anesthesia (group 1), from those obtained with traditional tenolysis
      performed under general anesthesia or total blockage of the brachial plexus
      (group 2), the authors conducted a prospective and controlled study. METHODS: 22
      patients with 39 fingers with flexor tendon injuries on zone 2 evolving to
      adherences were assessed. All patients were operated after three months and
      before one year of the primary tendinous suture. All patients showed limited
      active motion not improved by rehabilitation. Groups 1 and 2 showed to be
      homogenous concerning patients' age and gender, preoperative compromising, and
      absence of associated injuries or pathologies. All patients were assessed
      according to active motion (TAMs) both preoperatively and at 6 months
      postoperatively. RESULTS: The statistical analysis of data obtained for groups 1
      and 2 shows that the tenolysis performed with both techniques produce good
      results. By comparing the results for total active motion after six months of the
      tenolysis, group 1 patients (treated by the intraoperative awakening technique)
      were found to present better outcomes. CONCLUSIONS: Flexor tenolysis on zone 2
      provide good results in terms of joint range of motion. The intraoperative
      awakening technique with locoregional anesthesia provides improved outcomes when
      compared to the traditional technique.

PMID- 27022515
TI  - COMPARATIVE STUDY OF BONE NEOFORMATION USING AUTOLOGOUS GRAFTING AND THREE
      REPLACEMENTS: BONE DEFECTS IN RATS.
AB  - OBJECTIVE: Compare the percentage of bone neoformation promoted by autologous
      bone grafting and three kinds of replacement materials with different
      characteristics in rats' femoral holes. METHODS: Two holes measuring 5.4*2.7mm,
      were produced on each femur (right and left) of 14 isogenic Wistar rats. Each of
      the four defects produced was filled by autologous bone or by one of three tested
      materials-hydroxyapatite (HA), Genphos((r)) (HA+ beta-TCP) and GenMix((r)) (a
      combined bovine bone graft). In the end of the 6-week (n = 6) and 12-week (n = 8)
      periods, the animals were sacrificed. The sections (stained with Picro-Sirius)
      were assessed by optical microscopy and specific software. RESULTS: The groups
      with autologous bone were shown to be significantly superior to the others at
      both assessed times, showing a mean bone formation rate +/- SD of 90.6 +/- 10.8%
      in six weeks, and 98 +/- 9.2% in 12 weeks (p > 0.0001 for both assessed times).
      In six weeks, the results for the other groups were the following: Genphos((r)),
      46 +/- 7.1%; HA, 43.1 +/- 8.4%; and GenMix((r)), 57.3 +/- 4.5%. In 12 weeks:
      Genphos((r)), 47.8 +/- 11.1%; HA, 39.9 +/- 5.4%; GenMix((r)), 59.7 +/- 4.8%,
      significant (p = 0.007). CONCLUSIONS: In both assessed times, the three bone
      replacement materials tested in the study showed to be inferior to autologous
      bone graft for bone neoformation percentage.

PMID- 27022516
TI  - STIFF ELBOW TREATMENT BY INTERPOSING ARTHROPLASTY ASSOCIATED TO HINGED EXTERNAL
      FIXATOR.
AB  - OBJECTIVE: Assess the results of the elbow/fascia lata interposing arthroplasty
      technique associated to the use of a hinged external fixator in the treatment of
      stiff elbow. METHODS: Between 2001 and 2006, five cases of stiff elbow were
      operated and followed up by the Shoulder and Elbow Group of the Santa Casa
      Misericordia de Sao Paulo Medical Sciences School, establishing the following as
      inclusion criteria: patients with below-functional elbow range of motion
      associated to degeneration on that joint, for whom total prosthesis had not been
      indicated. Patients' ages ranged from 21 to 55 years (mean: 38). Male gender was
      prevalent (four cases), and, in all cases, the dominant side was operated.
      Concerning etiology, two cases of infectious arthritis sequels, one post-trauma
      sequel, and two rheumatoid arthritis were found. Preoperative range of motion
      ranged from 20 degrees  to 30 degrees  of flexion-extension; in two cases, fixed
      contracture existed in flexion at 30 degrees  and 65 degrees . The patients were
      assessed according to Bruce-modified AMA criteria. RESULTS: The mean follow up
      time was 54 months. All patients showed improvement of the Bruce index, which,
      preoperatively, was 43.5, increasing to 88.2 postoperatively. We found two
      excellent cases, one good, one fair, and one poor. CONCLUSION: Fascia lata
      interposing arthroplasty associated to the use of a dynamic external fixator on
      stiff elbows is a feasible alternative for patients not indicated to total elbow
      arthroplasty.

PMID- 27022517
TI  - DIAGNOSTIC AND THERAPEUTIC ARTHROSCOPY IN SYMPTOMATIC PATIENTS AFTER KNEE
      ARTHROPLASTY.
AB  - OBJECTIVES: Assess the worthiness of arthroscopy in investigating and treating
      knee pain after arthroplasty unexplained by clinical and subsidiary examinations.
      METHODS: Among 402 patients submitted to total or unicompartimental arthroplasty
      between September 2001 and April 2007 at a public university hospital, 17
      presented with pain on prosthetic articulation, without clear diagnosis by
      clinical, X-ray, laboratory, scintiscan, or nuclear magnetic resonance tests. All
      patients were submitted to arthroscopy and symptoms were assessed by using the
      Lysholm scale, comparing pre-and post-arthroscopy periods. Peroperative findings
      have been recorded. RESULTS: The procedure was effective for pain relief in 14 of
      17 patients (82.35%). The median for Lysholm scale climbed from 36 points before
      arthroscopy to 94 points after the procedure (p < 0.001). Most of the patients
      (12) were arthroscopically diagnosed with fibrosis known as "cyclop"; on the
      remaining five patients, anterior synovitis was found. All patients were treated
      by resection. CONCLUSIONS: Knee arthroscopy after arthroplasty in patients
      presenting unclear persistent pain shows localized arthrofibrosis ("cyclops") or
      synovitis, which can be treated by using the same procedure, resulting in pain
      relief.

PMID- 27022518
TI  - DISTAL FEMORAL VARUSING FOR OSTEOARTHRITIS OF VALGUS KNEE: A LONG-TERM FOLLOW-UP.
AB  - OBJECTIVE: Assess the long-term results of distal femoral varusing osteotomy and
      try to establish predictive criteria that could help on selecting patients to be
      submitted to this technique. METHODS: Fifteen patients with lateral compartment
      osteoarthritis and valgus deformity of the knee were submitted to distal femoral
      "V" varusing osteotomy fixated with lateral plate, pursuing knee alignment at 0
      degrees  on the anatomical axis. The mean follow-up period was 81.4 months,
      ranging from 43 to 132 months. The Knee Society Rating System protocol was
      employed. Additional assessed variables were the following: patient age, follow
      up time, and postoperative anatomical angle. RESULTS: 11 results were regarded as
      excellent or good (73%) and four as fair or poor (27%). CONCLUSION: Distal
      femoral "V" varusing osteotomy constitutes a good treatment alternative for
      patients with lateral compartment osteoarthritis and valgus knee. The following
      variables have not been confirmed: patient age at the time of surgery, follow-up
      time, and postoperative anatomical angle as predictive factors for the results.

PMID- 27022519
TI  - ARTHROSCOPY OF THE SCAPULOTHORACIC JOINT: CASE REPORTS.
AB  - Scapulothoracic arthroscopy is a procedure presenting restricted indications, for
      resecting free bodies, benign tumors, bursitis, and snaping scapula. The authors
      report four cases of scapulothoracic joint arthroscopy; in the first case, only a
      benign tumor (osteochondroma) could be visualized; in the second case,
      arthroscopic resection of an osteochondroma was found; in the third case,
      arthroscopic bursectomy due to scapulothoracic bursitis, and; in the fourth case,
      bursectomy and partial superomedial arthroscopic scapulectomy due to snaping
      scapula. 

PMID- 27022520
TI  - Editorial Personality.

PMID- 27022521
TI  - COMPLICATIONS IN HIP ARTHROSCOPY.
AB  - OBJECTIVES: To determine the prevalence of complications in a series of
      consecutive cases of hip arthroscopy; to assess the progression of the sample
      through a learning curve; and to recognize the causes of complications in
      arthroscopic hip operations. METHOD: 150 consecutive cases that underwent hip
      arthroscopy between May 2004 and December 2008 were evaluated. The complications
      encountered were classified in three ways: organic system affected, severity and
      groups of 50 consecutive cases. The data were analyzed by means of descriptive
      statistics and Fisher's exact test. RESULTS: We observed 15 complications in this
      study (10%): ten were neurological, two were osteoarticular, one was vascular
      ischemic and two were cutaneous. In the classification of severity, three were
      classified as major, 12 as intermediate and none as minor. The incidence of
      complications over the course of the learning curve did not present any
      statistically significant difference (p = 0.16). CONCLUSIONS: Hip arthroscopy is
      a surgical procedure that involves low morbidity, but which presents
      complications in some cases. These complications are frequently neurological and
      transitory, and mainly occur because of joint traction. The complication rate did
      not decrease with progression of our sample.

PMID- 27022522
TI  - WRIST ARTHRODESIS WITH MINIMAL FIXATION PRESERVING THE CARPOMETACARPAL JOINTS.
AB  - OBJECTIVE: Wrist arthrodesis is a surgical procedure that should always be
      considered in cases of pathological conditions in which anatomical and functional
      structures are altered. In general, the results are very satisfactory,
      particularly for pain relief, and in the majority of cases, there is considerable
      functional improvement. Various techniques have been described, with different
      methods of internal fixation, most of which include the carpometacarpal joints in
      the fusion. The objective of this study was to evaluate the results from wrist
      arthrodesis using a technique that is simpler, more biological, less expensive,
      and does not involve the carpometacarpal joints. METHODS: Fifteen patients with
      wrist arthrodesis were evaluated (six with sequelae from trauma, four with
      rheumatoid arthritis, three with Kienbock grade IV, one with Preiser and one with
      panarthrosis). The technique consisted of using an iliac bone plate and internal
      fixation with Kirschner wires, avoiding the carpometacarpal joints. RESULTS: The
      evaluation was based on consolidation time (93% in seven weeks); movements of the
      fingers and pronosupination; pinch and grasp strength; functional evaluation
      through the DASH, pain and patient satisfaction questionnaires. In general, the
      results were similar to those of other, more aggressive techniques, and the non
      inclusion of the carpometacarpal joints did not affect the final result.
      CONCLUSION: Wrist arthrodesis with fixation using Kirschner wires and an iliac
      bone plate, preserving the carpometacarpal joints, gives good or excellent
      results that are not inferior to those of other techniques that have been
      described. However, it presents major advantages over other methods: it is less
      aggressive and cheaper, and does not have the inconvenience and complications
      associated with the use of plates and screws.

PMID- 27022524
TI  - SPONDYLOLYSIS AND SPONDYLOLISTHESIS IN YOUNG GYMNASTS.
AB  - OBJECTIVE: To determine the incidence of spondylolysis and spondylolisthesis
      among female gymnasts, and to correlate these with lumbar pain, history of trauma
      and training load. METHOD: Eighteen competitive-level Olympic-style gymnasts aged
      8-17 years, with an average age of 11.3 years, were evaluated on a voluntary
      basis. The gymnasts answered a questionnaire about their sports activities and
      underwent a clinical examination and lumbar spine radiography. RESULTS: The
      radiographs were analyzed by orthopedists specializing in surgery of the
      vertebral column. The prevalence of spondylolysis was 5.56%, while no cases of
      spondylolisthesis were found. CONCLUSION: The incidence of the radiographic
      abnormalities identified was similar to what has been reported in the literature
      for non-athletic individuals, and the lumbalgia reported by these athletes did
      not show any direct relationship with spondylolysis and spondylolisthesis.

PMID- 27022523
TI  - EFFECT OF USING WRIST ORTHOSES ON FOREARM FLEXOR AND EXTENSOR MUSCLE ACTIVATION.
AB  - OBJECTIVE: To investigate the effect of using wrist immobilization orthoses made
      from different materials, on activation of the flexor and extensor musculature of
      the forearm while performing specific tasks. METHODS: Twenty-six adults, with an
      average age of 26.2 years, underwent the Jebsen-Taylor functional hand test and
      the grip strength test (Jamar((r)) dynamometer) under three conditions: free
      hand, wearing a composite orthosis and wearing a thermoplastic orthosis. The
      tests were carried out using the dominant hand only. During the tests, surface
      electrodes were attached to the flexor and extensor muscles of the forearm to
      record the muscle electrical activity. The results obtained under the three
      conditions were compared and analyzed using the Wilcoxon statistical test.
      RESULTS: Significant differences in muscle activation were found between using
      the free hand and using any of the orthoses. There was no significant difference
      in muscle activation between the two types of orthosis. A decrease in activity of
      the extensor muscles of the forearm was observed during all the tasks, as well as
      an increase in activation of the flexor muscles with the use of the orthoses.
      CONCLUSION: These results are important for defining whether an orthosis should
      be prescribed during the rehabilitation process for a wide range of disorders,
      such as tendinitis of the flexors and extensors of the wrist and fingers, as well
      as for predicting the length of time for which these devices should be used.

PMID- 27022525
TI  - FIXATION OF SUPRACONDYLAR FEMORAL FRACTURES: A BIOMECHANICAL ANALYSIS COMPARING
      95 degrees  BLADE PLATES AND DYNAMIC CONDYLAR SCREWS (DCS).
AB  - OBJECTIVE: To determine, by means of comparative biomechanical tests, whether
      greater compressive load resistance and flexion is presented by 95 degrees 
      angled blade plates or by dynamic condylar screws (DCS), and to correlate the
      failure type presented during the tests with each type of plate. METHODS: Sixty
      five porcine femurs were subjected to 1 cm medial wedge osteotomy, in the
      metaphysis, to simulate an unstable supracondylar femoral fracture.
      Osteosynthesis was performed on these pieces: 35 were fixed using 95 degrees 
      lateral blade plates and 30 with DCS plates. Another variable studied was the
      failure type presented in each group, in an attempt to correlate this with the
      type of plate. RESULTS: There were no statistically significant differences in
      biomechanical resistance between the two types of plates, or between the failure
      type and the plate type used for the osteosynthesis. CONCLUSION: The two types of
      plate behaved in a similar fashion. However, the angled blade plate proved to be
      superior to the DCS in the flexion test. No statistical difference in failure
      type or type of plate used was observed.

PMID- 27022526
TI  - SCREW MIGRATION IN TOTAL KNEE ARTHROPLASTY: CLINICAL REPORT.
AB  - Complications from total knee arthroplasty caused by the implanted material are
      rare, with the exception of polyethylene wear. Descriptions of screw migration
      into the knee joint cavity are very rare. The authors report intra-articular
      migration of a polyethylene safety screw in a case of total knee arthroplasty,
      with sacrifice of the posterior cruciate ligament (TKA Performance; Biomet,
      Warsaw, IN, USA), which necessitated new surgery to remove the screw, replace the
      polyethylene insert and emplace a new fixation screw. 

PMID- 27022527
TI  - TOTAL ANKLE ARTHROPLASTY: BRAZILIAN EXPERIENCE WITH THE HINTEGRA PROSTHESIS.
AB  - Ankle arthrosis is becoming more and more common. The search for solutions that
      preserve joint function has led to a new generation of prosthesis with three
      components and more degrees of freedom. This paper presents the results achieved
      for ten patients treated with the HINTEGRA Prosthesis (Integra, New Deal),
      through collaborative action between the Foot and Ankle Groups of the Orthopedics
      and Traumatology divisions of Escola Paulista de Medicina, Unifesp, and the
      School of Medicine of the University of Sao Paulo (USP). The ten patients (six
      women and four men, aged between 29 and 66 years), underwent a surgical procedure
      consisting of Hintermann's technique, between January and June 2005. They were
      evaluated at prearranged intervals, and the data were subjected to statistical
      analysis. The surgery led to a significant improvement in ankle mobility.
      Radiological evaluation showed no signs of loosening or failure in the prosthetic
      components in any of the patients studied. Although the complication rate in our
      sample was high, it was equivalent to the rates found by other authors, and
      directly represents the learning curve associate with this kind of procedure.
      Four years after the procedure, it was found that the patients pain levels had
      significantly decreased, and that their functional patterns had significantly
      improved, with AOFAS and Hintermann scores indicating results that were excellent
      for 20%, good for 70% and poor for 10%. Treatment of ankle arthritis by means of
      total arthroplasty using the HINTEGRA prosthesis was capable of providing good
      results over an average observation period of four years. 

PMID- 27022528
TI  - DYSPLASIA OF HIP DEVELOPMENT: UPDATE.
AB  - The term "developmental dysplasia of the hip" (DDH) includes a wide spectrum of
      abnormalities that affect the hip during its growth, ranging from dysplasia to
      joint dislocation and going through different degrees of coxofemoral subluxation.
      The incidence of DDH is variable, and depends on a number of factors, including
      geographical location. Approximately one in 1,000 newborn infants may present hip
      dislocation and around 10 in 1,000 present hip instability. Brazil has an
      incidence of five per 1,000 in terms of findings of a positive Ortolani sign,
      which is the early clinical sign for detecting the disorder. The risk factors for
      DDH include: female sex, white skin color, primiparity, young mother, breech
      presentation at birth, family history, oligohydramnios, newborns with greater
      weight and height, and deformities of the feet or spine. Hip examinations should
      be routine for newborns, and should be emphasized in maternity units. Among
      newborns and infants, the diagnosis of DDH is preeminently clinical and is made
      using the Ortolani and Barlow maneuvers. Conventional radiography is of limited
      value for confirming the diagnosis of DDH among newborns, and ultrasound of the
      hip is the ideal examination. The treatment of DDH is challenging, both for
      pediatric orthopedists and for general practitioners. The objectives of the
      treatment include diagnosis as early as possible, joint reduction and
      stabilization of the hip in a secure position. Classically, treatment options are
      divided according to different age groups, at the time of diagnosis. 

PMID- 27022529
TI  - SPORTS INJURIES OF THE UPPER LIMBS.
AB  - Sports injuries of the upper limbs are very common in physical activities and
      therefore, they need to be studied in detail, taking into consideration specific
      aspects of the types of sports practiced. Special attention should be paid to the
      dynamics of the shoulder girdle and the entire scapular belt, since the most
      appropriate treatment for athletes can only be provided in this manner. This can
      also help to prevent recurrences, which can occur in some cases because athletes
      always seek to return to their pre-injury level of sports activity. This article
      will focus primarily on the management of upper-limb tendon injuries, from the
      physiopathology through to the new methods of injury treatment that are more
      prevalent in sports practice in Brazil. 

PMID- 27022530
TI  - FRACTURES OF THE DISTAL EXTREMITY OF THE TIBIA TREATED WITH INTRAMEDULLARY NAIL
      OR BRIDGE PLATE: COMPARISON OF RADIATION EXPOSURE DURATION BETWEEN THE TWO
      METHODS.
AB  - OBJECTIVE: To compare the duration of exposure to radiation among patients with
      fractures of the distal third of the tibia treated with an intramedullary nail or
      with a bridge plate. METHODS: Intramedullary nails were used for 33 fractures,
      and bridge plates were used for 41 fractures. In the nail group, according to the
      AO classification, 14 patients had type A fractures, 15 had type B and four had
      type C. Twelve patients had closed fractures and 21 had open fractures. In the
      plate group, 10 patients had type A fractures, 22 had type B and nine had type C.
      Twenty-seven patients had closed fractures and 14 had open fractures. RESULTS:
      There was a significant difference in the duration of exposure to radiation
      between the patients treated using a nail and those treated using a plate (p =
      0.0001). The group treated using a nail had significantly greater exposure to
      radiation than did the group treated using a plate. Comparing the type of
      fracture (A, B or C), it was observed that there was no significant difference in
      the duration of exposure to radiation between the nail technique (p = 0.19) and
      the plate technique (p = 0.80). CONCLUSION: Fractures of the distal third of the
      tibia treated with an intramedullary nail present significantly greater exposure
      to radiation than do fractures treated with a bridge plate, independent of the
      fracture type.

PMID- 27022531
TI  - EVALUATION OF THE RESULTS FROM ARTHROSCOPIC TREATMENT OF THE LATERAL
      EPICONDYLITIS.
AB  - OBJECTIVE: To evaluate the results from patients with lateral epicondylitis
      following surgical treatment using the arthroscopy technique. METHODS: Twenty
      patients underwent surgery using the arthroscopic technique. Their ages ranged
      from 19 to 54 years (average of 41 years and eight months). Twelve (60%) of them
      were female and eight (40%) were male. The minimum follow-up period was 12 months
      and the maximum was 48 months, with an average of 20 months. All the cases were
      refractory to conservative treatment (rest and physiotherapy), with previous
      clinical treatment times ranging in duration from six to 136 months. To evaluate
      the results, we used the criteria of the American Medical Association (AMA), as
      modified by Bruce. RESULTS: We obtained 13 excellent results (65%) and seven
      moderate results (13%), with just one complication (reflex sympathetic
      dystrophy). This was the only patient who reported dissatisfaction. CONCLUSION:
      Surgical treatment of the lateral epicondylitis of the elbow using arthroscopy
      was a good option for 65% of the cases.

PMID- 27022532
TI  - TENDINOPATHY OF THE ANTERIOR COMPARTMENT OF THE ANKLE.
AB  - OBJECTIVE: To carry out a retrospective analysis on the etiopathogenesis,
      diagnosis and therapeutic options in cases of tendinopathy of the anterior
      compartment of the ankle. METHOD: 13 patients underwent surgery between September
      1998 and February 2009; ten men and three women. The right side was involved in
      twelve patients and the left in one. The mean age was 35 years (range 15-67). The
      etiology was traumatic in eight patients and degenerative (non-traumatic) in
      five. The mean time elapsed between diagnosis and treatment was 19 months (range
      1 - 60) and the mean length of follow-up was 34 months (range 4 - 127). The
      diagnosis was made through anamnesis and clinical examination. Magnetic resonance
      imaging was performed on nine patients, for staging and planning. The surgical
      treatment was personalized in each case (synovectomy, resection of the muscle
      belly, consolidation with the adjacent tendon, and free grafting of the
      semitendinosus tendon). The following scales were used to evaluate the results:
      1) subjective satisfaction scale, 2) AOFAS and 3) Maryland. RESULTS: In relation
      to the subjective satisfaction scale, 12 patients were satisfied and one was
      dissatisfied. The mean AOFAS score was 80 points, and the mean Maryland scale was
      86 points. CONCLUSION: Surgical treatment is effective for restoring function.
      The surgical techniques need to be personalized. The option of free grafting of
      the semitendinosus tendon is effective for gaps larger than five centimeters.

PMID- 27022533
TI  - EVALUATION OF HEPATIC FUNCTION AMONG PATIENTS UNDERGOING TOTAL HIP ARTHROPLASTY
      USING ENOXAPARIN.
AB  - OBJECTIVE: To evaluate hepatic changes resulting from the use of enoxaparin for
      prophylaxis of deep vein thrombosis among patients undergoing total hip
      arthroplasty. METHODS: Thirty-two patients underwent elective total hip
      arthroplasty, using enoxaparin, and were followed up for 65 days with serial
      hepatic enzyme assays. RESULTS: Changes in laboratory parameters were found in up
      to 75% of the patients during the study, but the parameters normalized after
      suspension of the treatment. No clinical evidence of hepatic lesions was found.
      CONCLUSION: The hepatic enzyme levels increase in most patients using enoxaparin,
      but without clinical correlation, and the levels normalize after suspension of
      the treatment.

PMID- 27022534
TI  - RADIOGRAPHIC STUDY ON THE ACROMION INDEX AND ITS RELATIONSHIP WITH ROTATOR CUFF
      TEARS.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between the
      lateral projection of the acromion and rotator cuff tears (RCTs) in the Brazilian
      population. METHODS: The lateral projection of the acromion was measured using
      anteroposterior radiographs of the shoulders, carried out with the glenoid cavity
      in absolute profile and the humeral head in the neutral position or with internal
      rotation. The acromion index (AI) was defined as the ratio between the distance
      from the plane of the glenoid cavity to the lateral edge of the acromion and the
      distance from the plane of the glenoid cavity to the lateral edge of the humeral
      head. This index was measured in 83 patients (mean age of 54 years) with RCTs and
      compared with a group of 28 individuals (mean age of 48 years) without RCTs. The
      presence or absence of RCTs was determined by means of magnetic resonance
      imaging. RESULTS: The mean AI was 0.7194 for the patients with RCTs and 0.6677
      for the individuals without RCTs, in the Brazilian population. This difference
      was statistically significant, with P < 0.001. CONCLUSION: A relationship can be
      established between AI and rotator cuff tears in the Brazilian population.

PMID- 27022535
TI  - TOTAL HIP ARTHROPLASTY WITH BIOMEC PROSTHESIS: 20-YEAR FOLLOW-UP.
AB  - OBJECTIVE: To analyze the clinical and radiological outcomes from total hip
      arthroplasty using the Biomec prosthesis over a 20-year period (1988 to 2009).
      METHODS: The patients were evaluated clinically in accordance with the Merle
      d'Aubigne and Postel functional classification, and underwent anteroposterior
      (AP) radiography of the pelvis and the operated joint in lateral view. The
      variables evaluated were acetabular and femoral osteolysis, polyethylene wear,
      nail migration, follow-up and clinical outcomes. RESULTS: The mean follow-up was
      10.6 years (range 4 to 21 years). The sample consisted of 84 patients (32 men and
      52 women) and the mean preoperative age was 47 years. We found that 88% of the
      results from the clinical evaluation were good or excellent. In relation to the
      radiological findings, 92.5% of the results were good. The mean wear on the
      polyethylene was 1.4 mm. CONCLUSION: The use of the Biomec prosthesis in this
      cohort showed good clinical and radiographic results.

PMID- 27022536
TI  - EVALUATION OF THE CERVICAL SPINE AMONG PATIENTS WITH RHEUMATOID ARTHRITIS.
AB  - OBJECTIVE: To evaluate the prevalence of cervical spine abnormalities among
      patients with rheumatoid arthritis and correlate the imaging findings with the
      clinical state. METHODS: A cross-sectional study on 35 patients was carried out
      at the School of Medicine of the Federal University of Goias (UFG) in 2004. The
      following were evaluated: age, use of medications and the clinical picture of
      pain and neurological characteristics. The erythrocyte sedimentation rate (ESR)
      and rheumatoid factor were tested, and radiographs of the cervical spine were
      produced in anteroposterior, lateral and dynamic views. To evaluate the influence
      of the variables on the emergence of instabilities, univariate and multivariate
      logistic regression tests were used (p < 0.05). RESULTS: Among the 35 patients
      evaluated, 13 (37.1%) presented a stable cervical spine. Out of the 22 patients
      with instability, six presented more than one type. Atlantoaxial instability was
      found in 15 patients, with a mean anterior atlantodental distance of 3.40 mm in
      the neutral lateral radiographic view and 6.54 mm in the lateral view with
      flexion. Basilar invagination was found in five patients and subaxial subluxation
      in seven patients. Two thirds of the asymptomatic patients had instabilities.
      Bicipital hyperreflexia presented statistically significant correlations with
      atlantoaxial instability (p = 0.024) and subaxial instability (p = 0.01). Age at
      diagnosis correlated with subaxial instability (p = 0.02). CONCLUSIONS: The
      prevalence of cervical instability was 62.9 % (22/35). The most frequent
      instabilities were: atlantoaxial subluxation (42.9 %), subaxial subluxation (20%)
      and basilar invagination (14.3%). The correlation between instabilities and
      clinical signs and symptoms was poor. The patients with subaxial subluxation
      presented disease onset at a younger age. Dynamic radiography was important for
      diagnosing atlantoaxial subluxation.

PMID- 27022537
TI  - SURGICAL TREATMENT OF OSTEOCHONDRAL LESIONS OF THE KNEE BY MEANS OF MOSAICPLASTY.
AB  - OBJECTIVE: To evaluate the functional results from the technique of mosaicplasty,
      in the knees of patients with osteochondral lesions. METHODS: Between August 1999
      and March 2005, 27 patients underwent mosaicplasty on their knees. Twenty-one
      were male and six were female. The patients' ages ranged from 16 to 64 years
      (mean of 38.1 years). Seventeen lesions were located on the right knee and ten on
      the left knee. The lesion was located on the lateral femoral condyle in four
      patients (15%), on the medial femoral condyle in 18 patients (66.5%) and on the
      patella in five patients (18.5%). The lesion sizes ranged from 1 to 8 cm(2) (mean
      of 2.7 cm(2)). The patients were evaluated before and after the operation using
      Lysholm's functional scale, with a mean follow-up of 2.5 years. RESULTS: Before
      the operation, the mean was 62.7 points, and after the operation, the mean was
      95.4 points. The patients who underwent mosaicplasty on the lateral femoral
      condyle presented a mean of 51.5 points before the operation, and a mean of 100
      points after the operation. In relation to the medial femoral condyle, the mean
      before the operation was 64.1 points, and it was 95.4 points after the operation.
      In relation to the patella, the mean before the operation was 66.4 points, and it
      was 92 points after the operation. CONCLUSION: Mosaicplasty proved to be a good
      alternative for treating osteochondral lesions of the knee. It presented better
      evolution in relation to lesions of the femoral condyles than in relation to
      lesions located on the patella.

PMID- 27022538
TI  - EVALUATION OF ANATOMICAL INTEGRITY USING ULTRASOUND EXAMINATION, AND FUNCTIONAL
      INTEGRITY USING THE CONSTANT & MURLEY SCORE, OF THE ROTATOR CUFF FOLLOWING
      ARTHROSCOPIC REPAIR.
AB  - OBJECTIVE: To evaluate the functional and anatomical results from surgical
      treatment via arthroscopy in cases of complete rupture of the rotator cuff, using
      ultrasound images and the Constant and Murley functional index to investigate the
      correlation between them. METHODS: 100 patients (110 shoulders) were evaluated.
      The mean follow-up was 48.8 +/- 33.28 months (12 to 141 months). The mean age was
      60.25 +/- 10.09 (36 to 81 years). Rupture of the supraspinal tendon alone
      occurred in 85 cases (77%), and in association with the infraspinatus in 20 cases
      (18%) and subscapularis in four shoulders (4%). An association of supraspinatus,
      infraspinatus and subscapularis lesions was found in one shoulder (1%). The
      lesions were classified according to DeOrio and Cofield scores as small/medium in
      85 shoulders (77%) and large/extensive in 25 (23%). The clinical results were
      assessed in accordance with the Constant and Murley criteria. The ultrasound
      results relate to reports issued by different radiologists. Statistical analysis
      was carried out using the chi-square test, Fisher's exact test, Student's t test,
      Pearson's correlation, Kruskal-Wallis correlation and logistic regression
      (significance: p < 0.05). RESULTS: The mean Constant evaluation was 85.3 +/-
      10.06 in the normal shoulders and 83.96 +/- 8.67 in the operated shoulders (p =
      0.224). Excellent and good results were found in 74 shoulders (67%), satisfactory
      and moderate results in 32 (29%) and poor results in four (4%). The ultrasound
      evaluation showed 38 shoulders with re-rupture (35%) and absence of rupture in 71
      (65%). Among the 74 shoulders (67%) with excellent/good results, 22 (30%)
      presented re-rupture in the ultrasound report (p = 0.294). Among the four
      shoulders (4%) with poor results, two (50%) presented reports of intact tendons
      (p = 0.294). CONCLUSION: There was no statistically valid correlation between the
      ultrasound diagnosis and the clinical evaluation of results among the patients
      who underwent arthroscopic repair to treat full tear lesions of the rotator cuff.
      The clinical results from the complete rotator cuff repairs via arthroscopy
      presented a high level of functional recovery (Constant 83.96), compared with the
      contralateral shoulder. The postoperative ultrasound reports presented a high
      percentage of re-rupture (35%). Postoperative strength was greater among the
      patients aged under 60 years (p = 0.002) and in cases of lesions less than or
      equal to 3 cm (p = 0.003).

PMID- 27022539
TI  - TREATMENT OF PARALYTIC HIP DISLOCATION AMONG SPASTIC QUADRIPLEGIC CEREBRAL PALSY
      PATIENTS BY MEANS OF FEMORAL AND PELVIC OSTEOTOMY, WITHOUT OPENING THE JOINT
      CAPSULE (CAPSULOPLASTY).
AB  - OBJECTIVES: To show the preoperative planning and results from surgical treatment
      for paralytic hip dislocation among patients with cerebral palsy. The techniques
      used were proximal femoral varus derotation osteotomy in association with Dega
      iliac osteotomy, without opening the joint capsule. METHODS: We performed a
      retrospective review of ten hips in eight patients with spastic quadriplegic
      cerebral palsy who underwent surgical treatment between 2003 and 2005, with the
      same surgical technique. The pre and postoperative clinical and radiological
      parameters, and the preoperative planning using an image intensifier, were
      assessed. The clinical parameters analyzed were: pain, hygiene-related
      difficulties and positioning difficulties. The radiological parameters were
      Reimer's index, the acetabular index and the neck-shaft angle. These results were
      subjected to statistical analysis. RESULTS: We obtained good results with this
      technique. After a mean follow-up of three years, all the hips were observed to
      be stable at the last assessment, and there was a high degree of satisfaction
      among the families in relation to the treatment. We also showed that preoperative
      planning using an image intensifier allowed us to reduce and stabilize these hips
      without the need for capsuloplasty. CONCLUSION: The authors conclude that in
      treating hip dislocation among spastic quadriplegic cerebral palsy patients,
      capsuloplasty is unnecessary for stabilizing the coxofemoral joint.

PMID- 27022540
TI  - MECHANICAL RESISTANCE OF THE PATELLAR LIGAMENT AFTER REMOVAL OF THE MIDDLE THIRD
      THROUGH EITHER ONE LONGITUDINAL INCISION OR TWO MINI-TRANSVERSE INCISIONS.
AB  - OBJECTIVE: To evaluate the resistance and regeneration of the patellar ligament
      after harvesting a graft for reconstruction of the anterior cruciate ligament,
      using the traditional technique of a single longitudinal skin incision or a
      technique of two transverse mini-incisions, in sheep. METHODS: Ten sheep were
      used. In the right knee, we removed the graft using the traditional method, and
      in the left knee, using the two-incision method. The animals were observed for
      six months. The specimens (patellar ligament, tibia and patella) were adapted to
      the mechanical test machine for ligament resistance tests. RESULTS: No difference
      was found between the two proposed techniques in relation to the regeneration and
      resistance of the patellar ligament. However, we observed that shortening of the
      patellar ligament occurred in both groups, and that suturing of the superficial
      fascia of the patellar ligament did not influence the regeneration of the
      patellar ligament, according to the histology. CONCLUSION: The technique using
      two incisions in the skin presents the same patterns of regeneration and
      resistance of the remaining patellar ligament as shown by the traditional
      technique of a single, longitudinal incision.

PMID- 27022541
TI  - INFORMED CONSENT: THE MEDICAL AND LEGAL CHALLENGE OF OUR TIME.
AB  - OBJECTIVE: To assess the real importance of obtaining informed consent, through
      an appropriate form, and its role in the outcome from civil liability claims.
      METHODS: The wordings of the current Brazilian law and jurisprudence were
      compared with rulings from the State Court of the State of Rio de Janeiro, in 269
      civil liability claims against healthcare professionals and hospitals. RESULTS:
      Favorable and unfavorable outcomes (i.e. acquittals and convictions) were
      compared, and possible variations in the verdicts were discussed in relation to
      whether informed consent forms had been filled out or not. CONCLUSIONS: Obtaining
      informed consent, by means of appropriate forms, is still not a widespread
      practice in the Brazilian healthcare or judicial systems. It is recommended that
      this practice be adopted in the manner described in this paper, since this is
      prescribed in Brazilian law.

PMID- 27022542
TI  - TRAUMATIC POSTERIOR DISLOCATION OF THE HIP IN CHILDREN:REPORT ON FIVE CASES.
AB  - OBJECTIVE: To evaluate a series of cases of traumatic posterior dislocations in
      children, with the treatment and results, and to review issues relating to the
      epidemiology, clinical and radiographic diagnosis, treatment, complications and
      prognosis of such cases. METHODS: Five patients with traumatic hip dislocation,
      with a mean age of 4.6 +/- 0.9 years and a follow-up period of 19.8 +/- 7.0
      months, were evaluated retrospectively. The time elapsed between dislocation and
      reduction, the type of treatment, the associated injuries and the subsequent
      complications were evaluated. RESULTS: The initial treatment was closed
      reduction, which was performed on average 5.2 +/- 3.6 hours after the initial
      trauma. All the patients underwent the reduction under anesthesia. The
      complementary treatment included plaster cast immobilization and traction. No
      need for additional surgery was observed and there were no long-term side
      effects. CONCLUSION: Traumatic dislocation of the hip should be treated quickly
      by means of closed reduction, with appropriate control over the reduction and
      rigorous observation in order to diagnose and treat late complications.

PMID- 27022543
TI  - MONOSTOTIC PAGET'S DISEASE IN LUMBAR VERTEBRAE: AN ATYPICAL LOCATION.
AB  - A 41-year-old white female patient with complaints of lumbar pain for more than
      three years, without irradiation, underwent several radiological examinations.
      Her condition was diagnosed by means of biopsy, as monostotic Paget' s disease in
      the third lumbar vertebra. This is an uncommon location. 

PMID- 27022544
TI  - The teaching of Orthopedics in medical schools in Brazil.

PMID- 27022545
TI  - OSTEOPOROSIS DIAGNOSIS AND TREATMENT.
AB  - Articles that update the state of knowledge regarding osteoporosis run the risk
      of quickly becoming obsolete because research and studies on osteoporosis today
      are arousing great interest among researchers, the pharmaceutical and medical
      equipment industries, governments and even WHO. All orthopedists know about
      osteoporosis because of its most deleterious effect: osteoporotic fracture.
      Osteoporosis without fractures does not arouse suspicion because this is a
      pathological condition with a nonspecific clinical profile. Osteoporotic
      fractures have an economic cost (from treatment), a social cost (from its
      sequelae) and a medical cost (from deaths). Many fractures could be avoided
      through diagnosing osteoporosis prior to the first fracture and thus many
      temporary and permanent disabilities could be avoided and many lives saved.
      Awareness of the risk factors for osteoporosis raises suspicions and bone
      densitometry aids in diagnosis. Treatment should be based on the physiopathology
      of the disease. Hence, for prevention or treatment of osteoporosis, the activity
      of osteoclasts should be diminished or the activity of osteoblasts should be
      increased, or both. Treatment that reduces the incidence of fractures by
      improving the bone geometry and microarchitecture would be ideal. Newly formed
      bone tissue needs to have good cell and matrix quality, normal mineralization, a
      good ratio between mineralized (mechanically resistant) and non-mineralized
      (flexible) bone, and no accumulated damage. The ideal treatment should have a
      positive remodeling rate and fast and long-lasting therapeutic effects. Such
      effects need to be easily detectable. They need to be safe. 

PMID- 27022546
TI  - PERIPROSTHETIC FRACTURES IN TOTAL KNEE ARTHROPLASTY.
AB  - The increasing number of total knee arthroplasties, in combination with the
      population's longer life expectancy, has led to a greater number of long-term
      complications. These add to the poor bone quality of elderly patients and often
      culminate in periprosthetic fractures. This complex orthopedic problem has a
      great diversity of clinical presentation. It may affect any of the bones in the
      knee and, because of the difficulty in finding solutions, may lead to disastrous
      outcomes. Its treatment requires that orthopedists should have broad knowledge
      both of arthroplasty techniques and of osteosynthesis, as well as an elaborate
      therapeutic arsenal including, for example, access to a bone bank. 

PMID- 27022547
TI  - THORACOLUMBAR BURST FRACTURE: LOAD SHARING CLASSIFICATION AND POSTERIOR
      INSTRUMENTATION FAILURE.
AB  - OBJECTIVES: To assess the relationship between sagittal collapse, posterior
      instrumentation failure and the McCormack classification among patients with
      thoracolumbar burst fractures who had undergone posterior arthrodesis more than
      one level above and one level below the fracture. METHODS: This was a
      retrospective review based on the medical records and radiographs of 26 patients
      who underwent operations between January 1990 and December 2006. The parameters
      assessed were: worsening of kyphosis (Cobb), neurological dysfunction (Frankel)
      and failure of surgical treatment (implant breakage or loosening). RESULTS: No
      relationship was found between sagittal collapse and the scoring in the McCormack
      classification (r = 0.221; P = 0.322). There was also no relationship between
      failure of the posterior implant and the scoring in this classification (p =
      0.85). CONCLUSION: Our findings suggest that this classification is not
      applicable to patients who underwent arthrodesis more than one level above and
      one level below the fracture.

PMID- 27022548
TI  - EVALUATION OF SURGICAL TREATMENT OF FRACTURES IN TWO OR THREE PARTS OF THE
      PROXIMAL HUMERUS WITH THE "PARACHUTE TECHNIQUE".
AB  - OBJECTIVE: To evaluate the efficacy and safety of the surgical technique called
      the "parachute technique, as applied to adult patients who suffered displaced and
      unstable two or three-part fractures of the proximal humerus, through the
      clinical outcomes. METHODS: Between January 1995 and June 2006, 59 adult patients
      with displaced and unstable two or three-part fractures underwent operations
      performed by the Shoulder and Elbow Group of the Orthopedics and Traumatology
      Service of Hospital do Servidor Publico Estadual de Sao Paulo using the
      "parachute technique. This method consists of an intramedullary tension band and
      extramedullary fixation in a figure-of-eight to join the fragments of the
      fracture, using a 6.5-millimeter spongy screw with partial threading, a washer
      and two non-absorbable wires, thereby producing stable synthesis with minimal
      aggression to the surrounding soft tissue and not requiring any subsequent
      removal of material. The final shape of this synthesis is reminiscent of the
      shape of an open parachute. The patients had a minimum postoperative follow-up of
      six months. For the diagnosis, trauma series radiographic views of the shoulder
      were produced. The fractures were classified in accordance with the system
      proposed by Neer. We used the scale of the University of California, Los Angeles
      (UCLA), to evaluate the results. RESULTS: The "parachute technique" produced good
      results in 47% and excellent results in 26% of the cases, according to the UCLA
      scores. CONCLUSION: The "parachute technique" is a safe and effective treatment
      for displaced and unstable two or three-part fractures of the proximal humerus.

PMID- 27022549
TI  - BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS.
AB  - OBJECTIVE: To induce growth of a neomeniscus into the pores of a prosthesis in
      order to protect the knee joint cartilage. METHODS: 70 knees of 35 New Zealand
      rabbits were operated. The rabbits were five to seven months old, weighed 2 to
      3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial
      meniscectomy in both knees during a single operation. A bioabsorbable polymeric
      meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer
      was implanted in one side. The animals were sacrificed after different
      postoperative time intervals. The femoral condyles and neomeniscus were subjected
      to histological analysis. Histograms were used to measure the degradation and
      absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and
      the degree of degradation of the femoral condyle joint cartilage. RESULTS: The
      data obtained showed that tissue growth histologically resembling a normal
      meniscus occurred, with gradual absorption of the prosthesis, and the percentages
      of chondrocytes on the control side and prosthesis side. CONCLUSION: Tissue
      growth into the prosthesis pores that histologically resembled the normal rabbit
      meniscus was observed. The joint cartilage of the femoral condyles on the
      prosthesis side presented greater numbers of chondrocytes in all its layers.

PMID- 27022550
TI  - OPEN DRAINAGE VERSUS PERCUTANEOUS DRAINAGE IN THE TREATMENT OF TROPICAL
      PYOMYOSITIS. PROSPECTIVE AND RANDOMIZED STUDY.
AB  - OBJECTIVE: To compare the results from treating tropical pyomyositis through
      percutaneous drainage of abscesses versus open surgical drainage of abscesses, by
      means of a randomized prospective study. METHODS: Twenty-five patients with
      tropical pyomyositis (Chiedozi grade II) were included in this study. They were
      randomized into two groups: group A (n = 13), treated with antibiotics and open
      drainage of the abscesses; and group B (n = 12), treated with antibiotics and
      percutaneous drainage of the abscesses. RESULTS: The mean age was 35.3 years (+/-
      19.2) in group A and 30.1 years (+/- 9) in group B (p = 0.41). There were eight
      female patients (61.5%) and five male patients (38.5%) in group A; in group B,
      three were female (25%) and nine were male (75%) (p = 0.11). Staphylococcus
      aureus was the microorganism most frequently found (72%). The mean hospital stay
      in group A was 12.7 days (+/- 2.3), and in group B, 10.6 days (+/- 1.6) (p =
      0.01). The mean duration of antibiotic use in group A was 12.2 days (+/- 2.3),
      and in group B, 10.1 days (+/- 1.5) (p = 0.02). CONCLUSION: Percutaneous drainage
      of the abscesses, in association with antibiotic therapy, is an efficient
      treatment method for tropical pyomyositis grade II, with shorter antibiotic use
      and hospital stay for patients.

PMID- 27022551
TI  - ANATOMICAL RELATIONSHIP OF THE SUPRASCAPULAR NERVE TO THE CORACOID PROCESS,
      ACROMIOCLAVICULAR JOINT AND ACROMION.
AB  - OBJECTIVE: To establish the anatomical relationship of the suprascapular nerve
      (SSN) located in the suprascapular notch, to the medial border of the base of the
      coracoid process, the acromial joint surface of the acromioclavicular joint and
      the anterolateral border of the acromion. METHODS: We dissected 16 shoulders of
      16 cadavers (9 males and 7 females). The distances from the suprascapular nerve
      (at its passage beneath the transverse ligament) to certain fixed points on the
      medial border of the base of the coracoid process, the acromial joint surface of
      the acromioclavicular joint, and the anterolateral border of the acromion were
      measured with the aid of calipers and correlated with age and sex. Cadavers with
      previous surgical interventions were excluded. RESULTS: The mean measurements
      from the notch of the suprascapular nerve were: 3.9 cm to the medial border of
      the base of the coracoid process (ranging from 3.1 cm to 5.2 cm); 4.7 cm to the
      acromioclavicular joint (ranging from 3.9 cm to 5.2 cm); and 6.1 cm to the
      anterolateral border of the acromion (ranging from 5.7 cm to 6.8 cm). CONCLUSION:
      Accurate anatomical knowledge of the nerves of the anterior region of the
      shoulder is essential in order to avoid iatrogenic injuries and to achieve
      satisfactory results in surgical treatment for shoulder diseases, whether
      performed as open or arthroscopic procedures.

PMID- 27022552
TI  - MACROSCOPIC ANALYSES OF THE EFFECTS OF HYALURONATES AND CORTICOSTEROIDS ON
      INDUCED OSTEOARTHRITIS IN RABBITS' KNEES.
AB  - OBJECTIVE: To evaluate the effects of intra-articular injections of
      corticosteroids, native hyaluronic acid and branched-chain hyaluronic acid in
      experimentally-induced osteoarthrosis. METHODS: 44 rabbits underwent anterior
      cruciate ligament resection and were then divided into four groups of eleven.
      Group 1: one intra-articular injection of saline solution per week, for three
      weeks; Group 2: three injections (one per week) of native hyaluronic acid; Group
      3: three injections (one per week) of branched-chain hyaluronic acid; Group 4:
      two injections of betamethasone with an interval of three weeks. The cartilage of
      the tibial plateaus was evaluated macroscopically twelve weeks after surgery.
      Changes to the joint surface were graded as follows: Grade 0: smooth joint
      surface without relief changes; Grade 1: rough surface without any depressions;
      Grade 2: similar to grade 1, but with depressions on the joint surface; and Grade
      3: subchondral bone exposure. The statistical analysis consisted of the use of
      Student's t test, chi-square test and analysis of variance (ANOVA). The
      significance level used was 5%. RESULTS: A statistical difference was found
      between the control group and the three study groups 2, 3, 4 in relation to the
      development and severity of arthrosis. However, there was no difference between
      the groups regarding the drugs studied. CONCLUSION: A similar degree of
      attenuation of the osteoarthrosis process in the rabbits' knees was found with
      the use of intra-articular injections of low-molecular-weight and high-molecular
      weight glycosaminoglycans, and the corticosteroid betamethasone, compared with
      placebo.

PMID- 27022553
TI  - REVISION TOTAL HIP ARTHROPLASTY USING A MODULAR CEMENTLESS DISTAL FIXATION
      PROSTHESIS: THE ZMR((r)) HIP SYSTEM. CLINICAL AND RADIOGRAPHIC ANALYSIS OF 30
      CASES.
AB  - OBJECTIVE: To evaluate the clinical and radiographic results from 30 cases of
      revision of total hip arthroplasty using a modular cementless distal fixation
      prosthesis: the ZMR((r)) Hip System. METHOD: Between July 2005 and December 2008,
      30 operations were performed, on 14 men and 14 women. Two male patients had
      bilateral surgery. The mean age was 59.2 years (29-81 years), with a mean follow
      up of 24 months. The Paprosky classification was used for periprosthetic bone
      loss, and the Harris Hip Score (HHS) was used to evaluate clinical results. On
      radiographs, distal migration of the femoral stem was defined in accordance with
      Sporer. Proximal bone remodeling was classified using the Callaghan criteria.
      RESULTS: The mean preoperative HHS was 39, and there was a significant increase
      to 93 points in the final evaluation, which indicated excellent clinical results.
      No femoral stem migration greater than 5 mm (Sporer) was observed on radiographs,
      thus suggesting that all the femoral prostheses presented osseointegration and
      remained stable from the time of the surgery until the final evaluation. The
      proximal femoral remodeling was either type B or type C in 29 hips, according to
      Callaghan. Seven patients had complications, but without interfering with
      osseointegration of the femoral components. CONCLUSION: Our results from revision
      of total hip arthroplasty using the ZMR((r)) Hip System were extremely
      encouraging, and all the components became osseointegrated and remained fixed at
      the time of the final evaluation.

PMID- 27022554
TI  - IINFLUENCE OF THE IMMUNOSUPPRESSANT TACROLIMUS (FK-506) ON THE FLEXURAL STRENGTH
      OF FEMUR: A STUDY IN RATS.
AB  - OBJECTIVE: To evaluate the resistance to femoral fractures among rats treated
      with the immunosuppressant tacrolimus FK-506 and compare these to untreated rats
      and rats treated with placebo. METHODS: Ninety male Wistar rats were used. The
      animals were nine weeks old and weighed between 220 g and 280 g. The
      immunosuppressive agent tacrolimus was used in this study at a dose of 2
      mg/kg/day, administered orally. The suspension was administered using an insulin
      syringe, and the maintenance therapeutic dose was sufficient to maintain the
      immunosuppressive activity. The animals were randomly divided into three groups
      (n = 30): group 1, no substance administered; group 2, administration of the
      immunosuppressant tacrolimus FK-506; and group 3, administration of the vehicle
      alone. Treatment with FK-506 was administered for 28 days. Total leukocyte counts
      and differential counts (lymphocytes, monocytes, eosinophils and neutrophils)
      were evaluated in order to monitor the immunosuppressive effect. Bone
      densitometry analysis by means of dual-energy x-ray absorptiometry (DXA) was also
      performed before and after administration of the drug. To evaluate the resistance
      to flexion, a support device was developed so that mechanical tests using an EMIC
      universal testing machine could be carried out. RESULTS: The results from the
      flexion resistance tests showed statistical differences between groups 1 and 2 (p
      = 0.001) and between groups 2 and 3 (p = 0.001). No statistical difference was
      found between groups 1 and 3 (p = 0.995). CONCLUSIONS: The femurs of rats treated
      with the immunosuppressive agent had lower mechanical strength than did those of
      normal rats and those that received placebo.

PMID- 27022555
TI  - TAPPING PILOT HOLE: MECHANICAL ANALYSIS OF SHEEP VERTEBRA AND THE ARTIFICIAL BONE
      MODEL.
AB  - OBJECTIVE: To determine the effect of pilot hole tapping, together with other
      variables such as pilot hole diameter, in relation to inner screw diameter and
      preparation method, on the insertion torque and pullout resistance of the screws
      used for anterior fixation of the cervical spine. METHOD: Twenty polyurethane
      test bodies and 30 thoracic vertebrae (T1-T5) were tested. Four holes were
      drilled into each test body: two of them with a diameter of 2.0 mm and two with a
      diameter of 2.5 mm. The holes were drilled using a bit or probe, according to the
      experimental group. Each experimental group was divided into two equal subgroups,
      with and without pilot hole tapping. In all, there were eight experimental
      groups: four using polyurethane specimens and four using sheep vertebrae.
      Cortical screws of 3.5 mm in outer diameter and 14 mm in length were inserted
      into the pilot holes. The insertion torque was measured during screw implantation
      and mechanical pullout tests were then performed using an Emic((r)) universal
      testing machine, with the Tesc 3.13 software, load cells of 1000 N, force
      application rate of 0.2 mm/min, preloading of 5 N and accommodation time of 10
      seconds. The property evaluated in the mechanical tests was the maximum pullout
      force. RESULTS AND CONCLUSION: Pilot hole tapping significantly decreased the
      insertion torque and pullout force of the screws in all the experimental groups.

PMID- 27022557
TI  - BILATERAL FIRST RIB FRACTURE IN A DIVE WITH LIFE VEST.
AB  - First-rib fractures are uncommon and are generally related to major thoracic
      trauma: so much so that they serve to indicate the severity of the trauma.
      Isolated bilateral first-rib fractures without major thoracic trauma are rarely
      described in the literature. The symptoms may go unnoticed and be minimized, thus
      making this condition difficult to diagnose. The present report presents a case
      of direct trauma on the supraclavicular region with symptoms of contusion of the
      brachial plexus, caused by a fall from a jet ski while a life vest was being
      used. The literature was reviewed to show the various facets of the problem and
      the treatment for this condition was discussed. 

PMID- 27022556
TI  - A FUNCTIONAL AND ROENTGENOGRAPHIC PRELIMINARY COMPARATIVE STUDY USING METAL
      BACKED AND ALL-POLYETHYLENE TIBIAL COMPONENTS IN TOTAL KNEE ARTHROPLASTY.
AB  - OBJECTIVE: To describe and clinically and radiographically compare patients who
      underwent total knee arthroplasty (TKA) with all-polyethylene (ALP) and metal
      backed (MTB) tibial implants. METHODS: Patients who underwent TKA between January
      1988 and December 2004 were grouped according to the type of implant received:
      all-polyethylene or metal-backed. Sixty patients came for evaluations, totaling
      82 operated knees. Among these, 22 patients had undergone TKA only with ALP (12
      unilateral and 10 bilateral cases), 33 patients only with MTB (26 unilateral and
      7 bilateral cases) and five patients underwent TKA with ALP in one knee and MTB
      in the other. The knees were divided thus: group 1, 37 knees with ALP; and group
      2, 45 knees with MTB. RESULTS: There were no differences in clinical or
      functional evaluations between the groups. The mean radiolucency in the femur was
      0.838 mm for the patients in group 1 and 0.356 mm for the patients in group 2 (p
      = 0.049). For the tibia, in the AP view, there was a mean value of 2.703 mm for
      group 1 and 0.733 mm for group 2 (p = 0.000). In the lateral view, the mean
      values for osteolysis was 0.405 mm for group 1 and 0.200 mm for group 2 (p =
      0.074). CONCLUSIONS: There were no differences between the groups in the
      functional and clinical evaluations. However, greater radiolucency was observed
      in the arthroplasties with ALP, both in the femur in the lateral view and in the
      tibia in the AP view. Level of evidence IV - case series study.

PMID- 27022558
TI  - INDIRECT ARTHROSCOPIC DECOMPRESSION OF SPINOGLENOID CYST WITH SUPRASCAPULAR
      NEUROPATHY: REPORT OF TWO CASES AND LITERATURE REVIEW.
AB  - Suprascapular nerve compression is rare and should be considered in the
      differential diagnosis of patients with shoulder pain and external rotation
      deficit. Spinoglenoidal cysts may cause compression, and posterosuperior glenoid
      labrum lesions are the most likely hypothesis to explain their appearance.
      Magnetic resonance imaging and electromyography define the diagnosis. Indirect
      arthroscopic decompression of the cyst and repair of the glenoid labrum enable
      complete neurological recovery. The authors report two cases of isolated
      paralysis of the infraspinatus muscle caused by compression due to spinoglenoidal
      cysts that were treated by means of arthroscopy, and present the pre and
      postoperative assessments. 

PMID- 27022559
TI  - THROMBOEMBOLIC COMPLICATION AFTER ARTHROSCOPIC SHOULDER SURGERY.
AB  - Although thromboembolic phenomena are frequent complications in lower-limb
      surgery, there are only two cases of pulmonary thromboembolism following shoulder
      arthroscopy in the literature. We describe the case of a 76-year-old patient with
      pulmonary embolism in both lungs after shoulder arthroscopy. No vascular
      abnormalities were found and no origin for the thrombus was detected. The exact
      cause of the thromboembolism remains unknown. 

PMID- 27022560
TI  - UPPER LIMB TRACTION DEVICE FOR ANTEROGRADE INTRAMEDULLARY LOCKED NAIL OF HUMERAL
      SHAFT FRACTURES.
AB  - Diaphyseal fractures of the femur and tibia in adults are mostly treated
      surgically, usually by means of intramedullary locked-nail osteosynthesis. Some
      comminuted and/or highly deviated shaft fractures may present a veritable
      technical challenge. Fracture (or orthopedic) tables, which enable vertical,
      horizontal and rotational instrumental stabilization of the limb, greatly
      facilitate reduction and implant placement maneuvers and are widely used by
      orthopedic surgeons. Humeral shaft fractures are mostly treated nonsurgically.
      However, some cases with indications that are well defined in the literature
      require surgical treatment. They can be fixed by means of plates or
      intramedullary nails, using anterograde or retrograde routes. In the humerus,
      fracture reduction and limb stabilization maneuvers for implantation of
      intramedullary nails are done manually, usually by two assistants. Because muscle
      fatigue may occur, this option may be less efficient. The aim of this paper is to
      present an external upper-limb traction device for use in anterograde
      intramedullary locked-nail osteosynthesis of humeral shaft fractures that enables
      vertical, horizontal and rotational stabilization of the upper limb, in a manner
      similar to the device used for the lower limbs. The device is portable, of simple
      construction, and can be installed on any operating table equipped with side
      rails. It was used for surgical treatment of 29 humeral shaft fractures using an
      anterograde locked intramedullary nail. Our experience was extremely positive. We
      did not have any complications relating to its use and we believe that it notably
      facilitated the surgical procedures. 

PMID- 27022562
TI  - MRI EVALUATION OF KNEE CARTILAGE.
AB  - Through the ability of magnetic resonance imaging (MRI) to characterize soft
      tissue noninvasively, it has become an excellent method for evaluating cartilage.
      The development of new and faster methods allowed increased resolution and
      contrast in evaluating chondral structure, with greater diagnostic accuracy. In
      addition, physiological techniques for cartilage assessment that can detect early
      changes before the appearance of cracks and erosion have been developed. In this
      updating article, the various techniques for chondral assessment using knee MRI
      will be discussed and demonstrated. 

PMID- 27022563
TI  - POST-TRAUMATIC STIFFNESS OF THE ELBOW.
AB  - Elbow stiffness is a common problem after joint trauma, causing functional
      impairment of the upper limb. The severity of the dysfunction depends on the
      nature of the initial trauma and the treatment used. Appropriate clinical
      evaluation and complementary examinations are essential for therapeutic planning.
      Several surgical techniques are now available and the recommendation must be made
      in accordance with patient characteristics, degree of joint limitation and the
      surgeon's skill. Joint incongruence and degeneration have negative effects on the
      prognosis, but heterotrophic ossification alone has been correlated with a
      favorable surgical prognosis. 

PMID- 27022564
TI  - STUDY OF THE TREATMENT OF FEMORAL HEAD FRACTURES.
AB  - OBJECTIVE: To establish guidelines for the treatment of femoral head fractures
      and to determine the best form of access in cases treated surgically. METHODS: We
      evaluated the clinical and radiological results from 13 patients (13 fractures)
      treated surgically, between May 1986 and July 1996, at the Department of
      Orthopedics and Traumatology, Santa Casa de Misericordia de Sao Paulo (SCMSP),
      Fernandinho Simonsen Wing. RESULTS: Out of six cases of Pipkin 1 fractures, five
      underwent resection of the fragment, resulting in four excellent and one good
      result. The good result had fixation of the fragment. Three patients presented
      Pipkin 2 fractures and all of them had fixation of the fragment, resulting in two
      excellent and one regular result. Two patients had Pipkin 3 fractures and
      underwent primary arthroplasty. Among the two patients with Pipkin 4 lesions, one
      was treated with reduction and osteosynthesis of the acetabular fracture, without
      addressing the head fragment, which had reduced significantly, resulting in early
      arthrosis; and the other patient was treated with total arthroplasty as the
      primary treatment. CONCLUSION: Upon comparing the literature review and our
      patients' treatment results, we concluded that femoral head fracture treatment
      needs to be surgical and that the choice of surgical access depends on the type
      of fracture.

PMID- 27022565
TI  - ANALYSIS OF CLINICAL AND FUNCTIONAL OUTCOME AND COMPLICATIONS OF TALAR NECK
      FRACTURES.
AB  - OBJECTIVE: To evaluate the clinical, functional and radiographic results from
      talar neck fractures in patients treated at the Foot and Ankle Surgery Group of
      Santa Casa de Sao Paulo. METHOD: We evaluated 20 patients. The mean follow-up
      time was 71 months. One fracture was classified as Hawkins Type I, 12 as Hawkins
      type II, five as Hawkins type III, two as Hawkins type IV and four fractures were
      open. RESULTS: One patient was treated conservatively, 16 were treated with open
      reduction and internal fixation (three with primary subtalar arthrodesis), one
      was treated with talectomy and two with tibiotalocalcaneal arthrodesis. The
      reduction obtained was anatomical in seven feet, acceptable in six feet and poor
      in four. Seven patients had early complications. There was one case of delayed
      consolidation and four of talar body osteonecrosis. Four patients required
      secondary reconstruction procedures. No significant radiographic impairment of
      the ankle joint was found in 62% of the patients and of the subtalar joint in
      25%. Of the patients who did not undergo secondary procedures, 81% complained
      about the treated foot, 37.5% showed some deformity, 44% presented diminished
      sensitivity and 50% had to retire from work. The mean loss of motion in the ankle
      was 49%, and in the subtalar joint, 80%. The average AOFAS score was 73 points.
      CONCLUSION: Talar neck fractures are associated with high rates of clinical,
      functional and radiographic complications.

PMID- 27022566
TI  - LOCALIZATION OF THE TIBIAL ENTRY POINT.
AB  - OBJECTIVE: To assess the intramedullary nail entry point in the proximal region
      of the tibia, through a questionnaire. METHODS: 230 participants undergoing
      treatment for tibial fractures were interviewed. The questionnaire was created
      with three sections that could be answered in a "Yes" or "No" format and a fourth
      section that had two figures representing anteroposterior (AP) and lateral view x
      rays that could be answered in an "A, "B" or "C" format. RESULTS: The most
      frequent reason was "ease of access" (67.8%), followed by "better nail insertion
      access" (60.9%) and, in third place, "to prevent knee pain" (27.4%). The reasons
      for choosing the access so as to "prevent knee pain" and "avoid tendinitis" had a
      significant relationship with points "A" and "C" of the schematic AP x-ray
      figure, especially "C" (medial tibial crest). There were no significant
      differences between the types of access to the patellar ligament in the schematic
      AP and lateral x-ray figures between age groups. CONCLUSION: The greater the age
      was, the larger the proportion choosing the question "to avoid valgus deformity"
      was. The reasons from a medical (practical) perspective related to the type of
      access in the transpatellar ligament, while the reasons from a patient
      (functional) perspective related to medial parapatellar access. Transpatellar
      access was chosen by most of the participants (66.5%).

PMID- 27022567
TI  - HEMIARTHROPLASTY IN THE TREATMENT FRACTURES OF THE FEMORAL NECK.
AB  - OBJECTIVE: To epidemiologically and clinically evaluate patients with displaced
      femoral neck fractures that were surgically treatment with cemented hip
      hemiarthroplasty. METHODS: All patients with displaced femoral neck fractures
      (Garden III and IV) who underwent cemented hip hemiarthroplasty using a unipolar
      prosthesis (Thompson), by means of a posterolateral access between June 2005 and
      September 2008 were retrospectively evaluated. RESULTS: Seventy patients were
      initially evaluated. Their mean age was 83.1 years. The patients were
      predominantly female (84.3%). Thirty-six patients were monitored as outpatients
      for periods ranging from 10 to 48 months (mean of 26.5 months). Fifteen patients
      were lost to follow-up. Nineteen patients died, and the mortality rate within the
      first year was 25.4%. Patients classified as ASA III had a mortality rate of
      25.7% and ASA II patients, a rate of 12.1%. Two patients had symptomatic deep
      vein thrombosis; one patient had an operative wound infection; and none of the
      patients presented hip dislocation. Most of the patients did not experience pain.
      Twelve patients (33%) showed deterioration of their walking ability. CONCLUSION:
      There were no cases of hip dislocation. Patients classified as ASA III had a
      higher mortality rate than did patients with ASA I or II. There was a worsening
      of walking ability in 33% of the patients. No revision due to loosening or pain
      was needed for any patient. Thirty patients did not present any pain (83.3%),
      four presented moderate pain (11.1%) and two presented intense pain (5.5%).

PMID- 27022568
TI  - A COMPARATIVE STUDY OF LUMBAR RANGE OF MOVEMENT IN HEALTHY ATHLETES AND NON
      ATHLETES.
AB  - OBJECTIVE: To compare the amplitude of trunk flexion and extension through
      goniometry among athletes and non-athletes and to correlate these data with the
      popliteal angle and hamstring muscle tests. METHODS: The amplitude of trunk
      flexion and extension was evaluated in 50 individuals who practiced sports on a
      regular basis and 50 non-athletes who did not present any painful lumber symptoms
      or any symptoms that could affect test performance. The measurements were made
      consecutively by two independent examiners by means of goniometry. The trunk
      flexion and extension values from the goniometry evaluation were correlated with
      the popliteal angle and hamstring flexibility tests, and the statistical
      correlation between them was analyzed. RESULTS: The mean values obtained were
      130.7 (101.9) for flexion and 40.2 (36.4) for extension. Statistically
      significant differences between the athletes and non-athletes were found in
      relation to the following parameters: goniometer in flexion with examiner 1,
      goniometer in flexion with examiner 2 and hamstring test. No statistically
      significant differences were found between the two groups in relation to the
      following parameters: goniometer in extension with examiner 1, goniometer in
      extension with examiner 2 and popliteal angle test. CONCLUSION: Individuals who
      practiced sports presented higher trunk flexion values. The use of goniometry to
      measure trunk amplitude showed variations in measurements between the examiners.

PMID- 27022569
TI  - PROSPECTIVE RANDOMIZED STUDY COMPARING TWO ANESTHETIC METHODS FOR SHOULDER
      SURGERY.
AB  - OBJECTIVE: To evaluate the efficacy of suprascapular nerve block in combination
      with infusion of anesthetic into the subacromial space, compared with
      interscalene block. METHODS: Forty-five patients with small or medium-sized
      isolated supraspinatus tendon lesions who underwent arthroscopic repair were
      prospectively and comparatively evaluated through random assignation to three
      groups of 15, each with a different combination of anesthetic methods. The
      efficacy of postoperative analgesia was measured using the visual analogue scale
      for pain and the analgesic, anti-inflammatory and opioid drug consumption.
      Inhalation anesthetic consumption during surgery was also compared between the
      groups. RESULTS: The statistical analysis did not find any statistically
      significant differences among the groups regarding anesthetic consumption during
      surgery or postoperative analgesic efficacy during the first 48 hours.
      CONCLUSION: Suprascapular nerve block with infusion of anesthetic into the
      subacromial space is an excellent alternative to interscalene block, particularly
      in hospitals in which an electrical nerve stimulating device is unavailable.

PMID- 27022570
TI  - ANATOMICAL STUDY OF THE MUSCULOCUTANEOUS NERVE IN RELATION TO THE CORACOID
      PROCESS.
AB  - OBJECTIVE: The authors performed an anatomical study on the path of the
      musculocutaneous nerve by dissecting 20 shoulders from 10 fresh adult cadavers.
      METHOD: The distance from the lower edge of the coracoid process to the point of
      penetration of the most proximal branch of the musculocutaneous nerve in the
      coracobrachialis muscle was measured and named the base. Starting from the
      inferomedial edge of the coracoid process, a second measurement was made to the
      point at which the lateral fascicle of the brachial plexus crossed the subclavius
      muscle, and was named the height. The third measurement was of the triangular
      area formed by the two first measurements, and was named the area. RESULTS: The
      mean base length was 3.42 cm, ranging from 2.38 cm to 4.40 cm. The mean height
      measurement was 2.74 cm, ranging from 1.03 cm to 3.80 cm. The mean area was 4.92
      cm(2), ranging from 1.22 cm(2) to 7.99 cm2. CONCLUSION: These measurements are
      very important because of the risk of injury to the musculocutaneous nerve in
      surgical approaches to the shoulder.

PMID- 27022571
TI  - EVALUATION OF THE RESULTS OF ARTHROSCOPIC ACL RECONSTRUCTION WITH AUTOGENOUS
      FLEXOR TENDONS.
AB  - OBJECTIVE: To evaluate the results from reconstruction of the anterior cruciate
      ligament (ACL) using with flexor tendon autografts from the thigh, with analysis
      on data relating to sex, body mass index (BMI) and associations with lower limb
      fracture. METHODS: A group of 265 patients who underwent knee arthroscopy for the
      purposes of ACL reconstruction using an ipsilateral graft from the flexor tendon
      of the thigh between July 6, 2000, and November 19, 2007, were evaluated.
      RESULTS: One hundred and seventy-six patients were evaluated over a mean period
      of 34.95 +/- 18.8 months (median: 31 months) (IQR: 20-48 months). The minimum
      evaluation period was 12 months and the maximum was 87 months. One hundred and
      thirty-eight patients (78.4%) had excellent results, 22 (12.5%) had good results,
      eight (4.5%) had fair results and eight (4.5%) had poor results. Higher incidence
      of good and excellent results for the following categories was not considered to
      be significant: males (p = 0.128), patients with BMI < 25 (p = 0.848), or
      patients with ACL injuries unrelated to an initial traumatic episode of lower
      limb fracture (p = 0.656). CONCLUSION: The ACL reconstruction technique using
      tendon autografts from the thigh showed good and excellent results for 91.4% of
      the sample. Male patients seemed to present a greater tendency towards good and
      excellent results. No statistically significant difference was found when the
      results were analyzed in relation to BMI or associations with initial traumatic
      fracture episodes in the lower limbs.

PMID- 27022572
TI  - MUSCLE TRANSFER FROM TRICEPS TO BICEPS IN PATIENTS WITH CHRONIC INJURY OF THE
      UPPER TRUNK OF THE BRACHIAL PLEXUS.
AB  - OBJECTIVE: To evaluate the results from transposition of the triceps for elbow
      flexion in patients with chronic and complete injury to the upper trunk of the
      brachial plexus. METHODS: This was a retrospective study, including only patients
      who had biceps grade 0 and triceps grade 5, who underwent anterior transfer of
      the triceps muscle, performed between 1998 and 2005. The affected side, sex, type
      of accident, strength of elbow flexion, complications and patient satisfaction
      were investigated in 11 cases. RESULTS: 10 patients were male; the age range was
      from 24 to 49 years, with a mean of 33.7 years. The minimum time between injury
      and surgery was 21 months (range 21-74 months). The left side was affected in
      eight cases, and the right only in three. Good results were obtained in 10
      patients, who acquired elbow flexion strength of grade 3 (two cases) and grade 4
      (eight cases), while one evolved unfavorably with grade 2 strength. Two cases had
      complications (initial compartment syndrome and insufficient tensioning). All the
      patients said that they were satisfied with the procedure. CONCLUSION: Anterior
      transposition of the triceps muscle provided patient satisfaction in all cases
      except one, attaining strength grade 4 in eight cases, grade 3 in two cases and
      grade 2 in one case.

PMID- 27022573
TI  - HEMIPELVECTOMY: ERASTO GAERTNER HOSPITAL'S EXPERIENCES WITH 32 CASES IN 10 YEARS.
AB  - OBJECTIVE: To show the experience of the Erasto Gaertner Hospital with
      hemipelvectomy surgery over a 10-year period. METHODS: This was a retrospective
      study on 32 patients who underwent hemipelvectomy at Erasto Gaertner Hospital
      between 1998 and 2008, assessing clinical and surgical characteristics. RESULTS:
      Among the 32 patients, 15 were female and 17 were male. The mean age was 37.94
      years. Eight cases showed involvement of the neurovascular bundle: three were
      located in the iliac and extended to the thigh, two were in the acetabulum and
      extended to the thigh and three were in the acetabulum and pubis. Twenty-three
      cases presented a neurovascular bundle free from neoplasia: 11 were restricted to
      the iliac, six were in the acetabular region, two were in the pubic ramus and
      four extended to the whole hemipelvis bone. One case involved the iliac-femoral
      vessels: one in the pubic ramus. Seven cases of chondrosarcoma and four cases of
      Ewing's sarcoma represented the majority. Eight cases underwent external
      hemipelvectomy and 24 underwent internal hemipelvectomy (11 were type I; four
      were type II; two were type II + III; three were type III and four were type IV).
      Of these 24 cases, 13 did not have any reconstruction, 10 had a fibular graft and
      one had an iliacfemoral vein and artery prosthesis. Twenty-six surgeries were
      curative and six were palliative. There were 14 deaths. Survival of two and five
      years was seen in 11 and 10 cases, respectively. For six cases, less than two
      years had passed since the operation. Three cases were lost during follow-up.
      CONCLUSION: This study shows the experiences of an oncology reference service
      specializing in highly complex surgical treatment.

PMID- 27022574
TI  - RESULTS OF ADDUCTORS MUSCLE TENOTOMY IN SPASTIC CEREBRAL PALSY.
AB  - OBJECTIVE: Radiographic evaluation of the evolution of hips that underwent soft
      tissue release. METHODS: This was a retrospective evaluation on 101 spastic
      cerebral palsy patients who underwent soft-tissue release between 1991 and 2006.
      Forty-four patients met the inclusion criteria: 23 boys and 21 girls; 34
      diparetic and 10 quadriparetic. Functionally, 29 were non-walkers, five were able
      to walk at home and 10 were able to walk within the community. Reimers' index
      (RI) and the acetabular index (AI) were measured on pre and postoperative
      radiographs, with a minimum follow-up of three years. The mean age at the time of
      surgery was 6.4 years. RESULTS: The results were considered good if the RI had
      reduced, or had increased by less than 10%. This was found in 52% of this study.
      We observed a clear improvement in IR, along with worse results in patients with
      more than five years of postoperative follow-up. CONCLUSION: Soft-tissue release
      should be performed as early as possible, regardless of age, walking condition,
      clinical type, RI, AI or sex, and as soon as the patient clinically presents less
      than 30 degrees  abduction, because of the benefits relating to walking,
      prevention and treatment of subluxation, hygiene and pain relief.

PMID- 27022575
TI  - CORRELATION BETWEEN AVASCULAR NECROSIS AND EARLY STABILIZATION OF PROXIMAL
      FEMORAL FRACTURES IN CHILDHOOD.
AB  - OBJECTIVE: We developed this study with the aim of evaluating the results from
      treating patients with proximal femoral fractures, in a series of cases. We
      sought to observe the influence of the most prevalent complications on the final
      results after a minimum follow-up of two years. We especially considered the
      relationship between establishment of avascular necrosis and the time between the
      accident and the therapeutic intervention. METHOD: We retrospectively studied
      proximal extremity fractures of the femur in 29 patients under 14 years of age
      between 1988 and 2007. We analyzed the following variables: sex, age, mechanism
      of injury, fracture classification (Delbet), treatment administered,
      complications (pseudarthrosis, varus deformity, leg length discrepancy and
      avascular necrosis), duration of surgery and results (Ratliff). We carried out
      individual descriptive analysis on each variable. The tests were used in
      accordance with the premise that normality applied. For the evaluation, we used
      Fisher's exact test. RESULTS: Five patients (17.2%) had avascular necrosis, and
      three of them (60.0%) were over 10 years of age. 73.3% of the patients treated
      within the first 24 hours showed good results. The most common cause of fractures
      was traffic accidents (44.8%). The best results were observed among patients who
      were treated surgically. 41.4% developed some type of complication. CONCLUSIONS:
      Among the 29 patients treated, 58.6% had good, 27.6% had regular and 13.8% had
      poor results, according to the Ratliff criteria. When conservative treatment was
      applied, only 17.0% had good results, while 69.3% had good results from surgical
      intervention. Likewise, 73.3% of the results were good results when surgery was
      performed within the first 24 hours and only 42.8% of the results were good among
      patients who underwent surgery after this period. Patients operated within the
      first 24 hours developed necrosis of the femoral head in 13.3% of cases, while
      21.4% of those operated after this period developed this complication.

PMID- 27022576
TI  - USE OF BIOCERAMICS IN FILLING BONE DEFECTS.
AB  - OBJECTIVE: To present the results from using biological ceramics for filling bone
      defects resulting from post-traumatic or orthopedic injuries. METHODS: Thirty-six
      patients with bone defects caused by trauma or orthopedic injury were evaluated.
      Nineteen patients were male (52.8%) and 17 were female (47.2%). Their ages ranged
      from 19 to 84 years, with a mean of 45.7 years and median of 37 years. Only
      patients with defects that required at least five grams of biological ceramic
      were included. Eighteen cases were classified as orthopedic: bone defects were
      observed in 11 cases of total hip arthroplasty; one case of primary total hip
      arthroplasty, due to coxarthrosis; five cases of femoral or tibial open wedge
      osteotomy; and one case of tarsal arthrodesis. There were 18 cases of trauma
      related defects; uninfected pseudarthrosis, eight cases; recent fractures of the
      tibial plateau with compression of the spongy bone, three cases; and exposed
      fractures treated with external fixators, seven cases. The surgical technique
      consisted of curetting and debriding the injury until bone suitable for grafting
      was found. Biological ceramic was then used to fill the defect and some kind of
      fixation was applied. RESULTS: Among the 36 patients evaluated, it was seen that
      35 (97.2%) presented integration of the biological ceramic, while one case of
      open fracture treated with external fixation had poor integration of the
      biological ceramic. CONCLUSION: Treatment of bone defects of orthopedic or post
      traumatic etiology using a phosphocalcium ceramic composed of hydroxyapatite was
      shown to be a practical, effective and safe method.

PMID- 27022577
TI  - RADIOGRAPHIC ASSESSMENT OF THE OPENING WEDGE PROXIMAL TIBIAL OSTEOTOMY.
AB  - OBJECTIVE: To radiographically evaluate individuals who underwent opening wedge
      proximal tibial osteotomy, with the aim of analyzing the proximal tibial slope in
      the frontal and sagittal planes, and the patellar height. METHOD: The study
      included 22 individuals who were operated at the National Traumatology and
      Orthopedics Institute (INTO) for correction of varus angular tibial deviation
      using the opening wedge osteotomy (OWO) technique with the Orthofix monolateral
      external fixator. Patients with OWO whose treatment was completed between January
      2000 and December 2006 were analyzed. The measurement technique consisted of
      using anteroposterior radiographs with loading and lateral views with the
      operated knees flexed at 30 degrees . RESULTS: There were no statistically
      significant differences between the pre and postoperative tibial slope and
      patellar height values in the patients evaluated. CONCLUSION: Opening wedge
      proximal tibial osteotomy is a technique that avoids the problems presented by
      high proximal tibial osteotomy, since it is done without causing changes to the
      extensor mechanism, ligament imbalance or distortions in the proximal tibia.

PMID- 27022578
TI  - BIOMECHANICAL AND HISTOLOGICAL ANALYSIS OF THE GASTROCNEMIUS IN RATS SUBJECTED TO
      MUSCLE INJURY AND TREATMENT WITH LOW-LEVEL LASER THERAPY.
AB  - OBJECTIVE: To mechanically and histologically evaluate the application of low
      level laser therapy to the reparative process on lesions caused by impact on the
      gastrocnemius muscles of rats. METHODS: 45 female Wistar rats were divided into
      three groups (n=15/ group): C (control, no lesion), ML (muscle lesion) and ML-L
      (muscle lesion and laser therapy). The experimental muscle lesion was produced by
      letting a 250 g load drop from a height of 30 cm, directly onto the muscle. The
      animals in the ML-L group were subjected to application of 960 nm laser, 2
      J/cm(2), on the lesion site, for three days, twice a day. Mechanical tests were
      performed on an Emic((r)) universal testing machine. RESULTS: The mean values for
      the maximum force were: 35.70 (+/- 2.69) N in group C, 31.77 (+/- 2.59) N in
      group ML and 34.36 (+/- 3.63) N in group ML-L, with a statistically significant
      difference between groups C and ML (p < 0.05). The mean values for relative
      stiffness were: 3.75 (+/- 0.98) N/mm in group C, 3.84 (+/- 0.32) N/mm in group ML
      and 4.43 (+/- 0.68) N/mm in group ML-L, with no statistically significant
      differences (p>0.05). Histological analysis showed the presence of blood vessels
      in group ML-L and hematomas during the repair process. CONCLUSION: Laser therapy
      had a positive effect on the regeneration process of the muscle injury.

PMID- 27022579
TI  - AUTOLOGOUS CHONDROCYTE TRANSPLANTATION-SERIES OF 3 CASES.
AB  - Hyaline cartilage covers joint surfaces and plays an important role in reducing
      friction and mechanical loading on synovial joints such as the knee. This tissue
      is not supplied with blood vessels, nerves or lymphatic circulation, which may be
      one of the reasons why joint cartilage has such poor capacity for healing.
      Chondral lesions that reach the subchondral bone (osteochondral lesions) do not
      heal and may progress to arthrosis with the passage of time. In young patients,
      treatment of chondral defects of the knee is still a challenge, especially in
      lesions larger than 4 cm. One option for treating these patients is autologous
      chondrocyte transplantation/implantation. Because this treatment does not violate
      the subchondral bone and repairs the defect with tissue similar to hyaline
      cartilage, it has the theoretical advantage of being more biological, and
      mechanically superior, compared with other techniques. In this paper, we describe
      our experience with autologous chondrocyte transplantation/implantation at the
      Institute of Orthopedics and Traumatology, Hospital das Clinicas, University of
      Sao Paulo, through a report on three cases. 

PMID- 27022580
TI  - PARSONAGE-TURNER SYNDROME: CASE REPORT OF A HIV-SEROPOSITIVE PATIENT.
AB  - Parsonage-Turner Syndrome is a rare disease that affects the musculature of the
      scapular girdle, leading to muscle atrophy and large motor deficit. The etiology
      is uncertain, but it is believed that infectious and autoimmune factors are
      involved. The diagnosis is made by exclusion, and the main differential diagnoses
      are cervical disc hernias, rotator cuff injuries and rheumatic diseases. During
      diagnostic investigations, we perform laboratory tests, radiographs and MRI on
      the shoulders and cervical spine, with emphasis on electroneuromyography to help
      in making a definitive diagnosis. This case report is presented because it shows
      a disease that is rarely associated with HIV seropositivity and the importance of
      early diagnosis for better treatment of these patients. 

PMID- 27022581
TI  - ACUTE ISOLATED ANTEROLATERAL DISLOCATION OF THE PROXIMAL TIBIOFIBULAR JOINT.
AB  - Isolated traumatic dislocation of the proximal tibiofibular joint is rare. This
      injury may go unrecognized or be misdiagnosed at the initial presentation. Lack
      of clinical suspicion can cause diagnostic problems. The diagnosis requires an
      accurate history of the mechanism and symptoms of the injury, and adequate
      clinical and radiographic evaluation of both knees. Unrecognized cases are a
      source of chronic abnormalities. The treatment consists of closed reduction and
      immobilization or, in non-reducible or unstable cases, open reduction with
      temporary internal fixation. A rare case of isolated proximal tibiofibular
      dislocation in a basketball player is reported to illustrate this injury. 

PMID- 27022582
TI  - A big RBO.

PMID- 27022583
TI  - PAIN FOLLOWING TOTAL KNEE ARTHROPLASTY - A SYSTEMATIC APPROACH.
AB  - Total knee arthroplasty (TKA) is known to be a successful procedure. The aging of
      the population and the growing demand for quality of life have greatly increased
      the indications for the procedure. Nonetheless, TKA presents some complications
      that still lack definitive resolution. Pain after TKA is caused by a myriad of
      reasons that need to be systematically studied in order to reach the correct
      diagnosis and treatment. History, physical examination, laboratory tests and
      imaging examinations must all be included in the workup and repeated until a
      plausible reason has been identified, since if pain is the only indication for
      TKA revision, the results may be catastrophic. 

PMID- 27022584
TI  - MALE OSTEOPOROSIS.
AB  - Population aging is a reality that is being faced worldwide, and Brazil is no
      different. Osteoporosis was considered to be a postmenopausal women's disease for
      many years. Men have many development and hormonal factors that differentiate
      their skeletal maturation, which affects the incidence of osteoporosis and
      fractures. An up-to-date review of the specific literature within the Medline
      system is presented. 

PMID- 27022585
TI  - EVOLUTION OF SLIPPED CAPITAL FEMORAL EPIPHYSIS AFTER NONSURGICAL TREATMENT.
AB  - To evaluate the efficacy of conservative treatment of patients with slipped
      capital femoral epiphysis (SCFE) and the complications due to the progression of
      the disease. METHODS: 18 patients (26 hips) seen consecutively from December 1996
      to August 2006 at the Orthopedics Service of Santa Casa de Misericordia de Sao
      Paulo, who had been referred from other services with a diagnosis of SCFE and
      were treated without surgery, were retrospectively analyzed. RESULTS: Slip
      progression occurred in 19 hips (73%). Among the mild cases, eight remained mild,
      four became moderate and one became severe, according to the Southwick
      classification. Four out of the six originally moderate cases became severe and
      the two already severe cases worsened. CONCLUSION: Although today there is a
      consensus regarding the indication of surgical treatment for SCFE to prevent
      progression, some cases with confirmed diagnoses are still being treated
      conservatively. This is a major error, since it implies increased morbidity of
      the disease.

PMID- 27022586
TI  - OPEN REDUCTION OF HIP DISLOCATION IN PATIENTS WITH ARTHROGRYPOSIS MULTIPLEX
      CONGENITA - AN ANTEROMEDIAL APPROACH.
AB  - To evaluate the results from surgical treatment of hip dislocation through the
      anteromedial approach, in patients with arthrogryposis multiplex congenita (AMC).
      METHODS: The medical files and radiographs of seven children with AMC who
      presented hip dislocation (total of 10 dislocated hips) were retrospectively
      reviewed. Pre and postoperative joint mobility was evaluated by summing the joint
      range of motion in flexion and abduction. The acetabular angle and height of the
      femoral neck before the operation, and the continuity of the Shenton arc, Sharp
      angle and center-edge (CE) angle after the operation, were evaluated
      radiographically. When avascular necrosis was identified, it was classified in
      accordance with Ogden and Bucholz. RESULTS: The mean age of the children at the
      time of the surgery was 5.5 months (range: 3 to 11 months). The mean duration of
      follow-up for the patients was 9.5 years (range: 2 to 13 years). The mean
      amplitude of the sum of the joint range of motion in flexion and abduction in the
      preoperative examination was 108 degrees  (range: 70 degrees  to 155 degrees )
      and postoperatively, it was 125 degrees  (range: 75 degrees  to 175 degrees ). In
      the last evaluation, eight hips were found to be centered and two were
      subluxated. Two hips had been subjected to Salter iliac osteotomy. Two hips (20%)
      had presented significant signs of Ogden type IV avascular necrosis. Eight hips
      had good results while two were fair. CONCLUSION: We consider that the
      anteromedial approach is a good option for treating hip dislocation in very young
      patients with arthrogryposis multiplex congenita.

PMID- 27022587
TI  - COMPLICATIONS OF THE SCREW/WASHER TIBIAL FIXATION TECHNIQUE FOR KNEE LIGAMENT
      RECONSTRUCTION.
AB  - To evaluate the presence of pain at the site of the surgical incision and the
      need to remove the tibial fixation screw in anterior cruciate ligament (ACL)
      reconstruction, in relation to sex and body mass index (BMI). METHODS: A group of
      265 patients who underwent ACL reconstruction with ipsilateral flexor tendon
      grafts from the thigh in which the tibial fixation technique consisted of using a
      cortical screw and metal washer, between July 2000 and November 2007, were
      evaluated. RESULTS: 176 patients were evaluated for an average of 33.3 +/- 19.5
      months; median of 29.5 months; IIQ: 17-45 months; minimum of 8 and maximum of 87
      months. There was no statistical difference regarding complaints of pain at the
      site of the screw (p = 0.272) and the need to remove the tibial screw (p = 0.633)
      between sexes. There was no statistical difference regarding complaints of pain
      at the site of the screw (p = 0.08) and the need to remove the tibial screw (p =
      0.379) according to BMI. CONCLUSION: The pain complaint rate at the screw site
      from the screw and metal washer method used for tibial fixation in ACL
      reconstruction was of the order of 25%, and the screw had to be removed in 10.8%
      of the cases. There was no predominance of pain complaints at the surgical wound
      between the sexes. There was a greater tendency to complain about pain among
      patients with BMI < 25. There was no predominance of screw and washer removal
      between the sexes or between individuals with different BMIs.

PMID- 27022588
TI  - TOURNIQUET VERSUS NO TOURNIQUET USE IN KNEE VIDEOARTHROSCOPY: A MULTICENTRIC,
      PROSPECTIVE, DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL.
AB  - To evaluate whether, by using an arthropump (irrigation equipment with pressure
      sensor), pneumatic tourniquet use could interfere with the duration of surgery,
      recovery of movement and joint volume in patients who underwent knee
      videoarthroscopy for partial meniscectomy. METHODS: 103 patients divided randomly
      into two groups regarding use or nonuse of a pneumatic tourniquet were evaluated
      in five different centers by seven different surgeons. The variables were
      evaluated during the surgery and seven days after the operation. RESULTS: No
      statistically significant differences were found among any of the variables
      studied. CONCLUSION: There are no reasons that would either justify or discredit
      tourniquet use in this specific situation.

PMID- 27022589
TI  - COMPARISON OF COMPLEMENTARY EXAMS IN THE DIAGNOSIS OF ROTATOR CUFF INJURIES.
AB  - The aim of this study was to evaluate the accuracy of simple radiography,
      ultrasound and magnetic resonance imaging (MRI) in diagnosing rotator cuff
      injuries, comparing their findings with open or arthroscopic surgery findings.
      METHODS: Protocols of the Shoulder and Elbow Surgery Service for patients
      undergoing surgical treatment for rotator cuff injuries diagnosed by means of
      radiography, ultrasound and/or MRI between 2002 and 2007 were evaluated. Based on
      the data gathered, we analyzed the sensitivity, specificity, positive predictive
      value, negative predictive value and accuracy of these complementary
      examinations, compared with the findings during the surgical procedures. RESULTS:
      This study included 147 patients with a mean age of 46.09 years. All the patients
      had undergone a radiography examination, 101 had undergone ultrasound examination
      and 72 had undergone MRI. We found sensitivity of 13.8%, specificity of 2.6% and
      accuracy of 30% with radiography; sensitivity of 57.6%, specificity of 29.6% and
      accuracy of 51.4% with ultrasound; and sensitivity of 86.6%, specificity of 22.2%
      and accuracy of 63.3% with MRI. CONCLUSION: Radiography was found to be a
      specific examination when the mirror sign was present. MRI and ultrasound were
      shown to be reliable methods with high accuracy for diagnosing rotator cuff
      injuries.

PMID- 27022590
TI  - FUNCTIONAL EVALUATION OF PATIENTS WHO HAVE UNDERGONE ARTHROSCOPIC DEBRIDEMENT TO
      TREAT MASSIVE AND IRREPARABLE TEARS OF THE ROTATOR CUFF.
AB  - To evaluate the results from patients who underwent arthroscopic debridement of
      extensive irreparable rotator cuff injuries. METHODS: 27 patients were operated
      between 2003 and 2007, and 22 of them were evaluated. The surgical procedure
      consisted of arthroscopic debridement of the stumps of the tendons involved,
      bursectomy, removal of acromial osteophytes and, possibly, biceps tenotomy and
      tuberoplasty. RESULTS: All the patients showed involvement of the supraspinatus
      and infraspinatus tendons at the preoperative stage. In the postoperative
      evaluation, 14 patients had a complete teres minor muscle, and three had partial
      tears of the subscapularis tendon. There was an improvement in the UCLA criteria,
      from 15 preoperatively to 31 postoperatively. There was no improvement in muscle
      strength, but there was a reduction in the pain. CONCLUSION: Arthroscopic
      debridement is a recommended procedure for elderly patients with irreparable
      rotator cuff tears, good range of motion and low functional demand, when the main
      objective is to diminish pain.

PMID- 27022591
TI  - ARTHROSCOPIC TREATMENT OF CALCIFYING TENDINITIS OF THE ROTATOR CUFF.
AB  - To evaluate the clinical and radiographic results from arthroscopic surgical
      treatment of the rotator cuff in patients with calcifying tendinitis. METHOD: A
      retrospective study was conducted on twenty patients who underwent arthroscopic
      treatment for calcifying tendinitis of the shoulder between March 1999 and
      November 2005. Six patients were excluded due to loss of follow-up. The average
      follow-up period was 41.4 months. Eight patients (57%) were female and six (43%)
      were male. The right side was affected in 10 cases (71%) and the left in four
      cases (29%). Nine cases (64%) had calcification in the supraspinatus tendon, two
      (14%) in the infraspinatus tendon, and three (21%) in both tendons. RESULTS: In
      all cases, resection of the calcium deposits was performed by means of a needle
      (Jelco(r) No. 14) in combination with curettage (mini-curette). Two shoulders
      (14%) underwent subacromial decompression, and one (7%) underwent excision of the
      distal clavicle. A tendon-tendon suture was performed in three shoulders (21%).
      None of the patients underwent tendon-bone reinsertion. The mean score obtained
      on the UCLA scale was 33 points (26-35), thus indicating that a majority of
      patients had good results. In the final radiographic evaluation, none of the
      patients showed signs of calcification. CONCLUSION: Arthroscopic treatment of
      calcifying tendinitis of the shoulder safely allows excision of the
      calcification, leading to good results in relation to shoulder pain and function.

PMID- 27022592
TI  - PROSPECTIVE COMPARATIVE STUDY BETWEEN PROXIMAL TRANSVERSE INCISION AND THE
      CONVENTIONAL LONGITUDINAL INCISIONS FOR CARPAL TUNNEL RELEASE.
AB  - Carpal tunnel syndrome (CTS) is a pathological condition frequently seen in
      orthopedic consultation offices. It is most common compressive neuropathy and
      also the one most often treated surgically. CTS is usually diagnosed clinically,
      through the clinical history, physical examination (Tinel, Phalen and Durkan
      tests) and complementary examinations, and more specifically, nerve conduction
      studies. Ultrasound scans and magnetic resonance imaging may also be used.
      Conservative treatment is reserved for patients presenting with mild symptoms,
      with little incapacitation, who show good response to non-steroidal or steroidal
      anti-inflammatory drugs, physiotherapy and lifestyle changes. Surgical treatment
      is more frequent, and a variety of techniques are used. The goal of the surgery
      is to decompress the carpal tunnel and, by sectioning the transverse carpal
      ligament, release the median nerve. The aim of this paper was to compare surgical
      treatment of CTS by means of a transverse mini-incision made proximally to the
      carpal canal, with the classic longitudinal incision over the carpal canal. The
      mini-incision technique was shown to be less invasive and equally effective for
      treating CTS, with less morbidity than with the classic longitudinal incision. 

PMID- 27022593
TI  - NOSOLOGY OF HAND DISEASES IN CHILDREN AND ADOLESCENTS OPERATED IN PROVISIONAL
      FACILITIES IN A MODEL HOSPITAL - PERNAMBUCO STATE, BRAZIL.
AB  - To report the frequencies of congenital hand diseases in patients who underwent
      surgery on a collective mobilization basis at SOS Hand, Recife, Pernambuco,
      between 2005 and 2009. METHODS: Information was collected from 833 children and
      adolescents who were examined in eight missions. RESULTS: Among the patients, 306
      (36.7%) underwent surgery: 240 (78.4%) because of congenital malformation and 66
      (21.6%) because of acquired lesions. The most frequent congenital malformations
      were: syndactyly, 72 cases (30.0%); polydactyly, 30 cases (12.5%); bifid thumb,
      19 cases (7.9%); complex hand malformation, 14 cases (5.8%); cleft hand, 13 cases
      (5.4%); trigger finger, 12 cases (5.0%); camptodactyly, 11 cases (4.6%); and
      brachysyndactyly, 9 cases (3.7%). The most frequently acquired injuries were:
      obstetric traumatic lesions, 26 cases (39.4%); hand trauma sequelae, 18 cases
      (27.3%); cerebral paralysis sequelae, 7 cases (10.6%); electric shock sequelae, 5
      cases (7.6%); and burn sequelae, 4 cases (6.1%). CONCLUSION: The nosology of hand
      diseases is similar to that of large series of elective surgery, especially
      regarding congenital deformities. The frequency of acquired hand lesions seems to
      be higher than the frequency in international series. The collective mobilization
      system for hand surgery is important for decreasing the need for this activity in
      public institutions, and it has been shown to be very efficient. The success of
      the project may provide support for the Brazilian National Health System to
      enroll hand surgeons in the on-call system, in emergency units.

PMID- 27022594
TI  - DESCRIPTIVE STUDY ON SAGITTAL LUMBAR SPINE CHANGES IN STUDENTS OF THE FEDERAL
      EDUCATIONAL SYSTEM OF FLORIANOPOLIS.
AB  - The purpose of this study was to assess the prevalence of sagittal lumbar spine
      postural abnormalities and associated factors among students in the federal
      educational system in Florianopolis. METHODS: 288 adolescents (156 males and 132
      females), aged from 15 to 18 years, who were students in the federal educational
      system in Florianopolis, Santa Catarina, were evaluated. To gather data,
      photogrammetry was used following a specific protocol for postural assessment,
      and a questionnaire was used to identify the prevalence and frequency of pain,
      and the activities that triggered the problem. In the data analysis, descriptive
      statistics, Student's t-test for independent samples, chi-square test and
      Poisson's regression were used, with the significance level set at p<0.05 for all
      the tests. RESULTS: The prevalence of low back pain was 49.3%, with weekly
      frequency in 43.1% of the sample. The prevalence of deviation was 53.8%, and
      90.9% corresponded to rectification of lumbar curvature, and this affected males
      more frequently. A significant difference in lumbar angle was found between the
      sexes; higher prevalence ratios of postural deviations were found in the male
      group. CONCLUSIONS: The prevalences of low back pain and lumbar postural
      deviation were high, but the relationship between these variables did not present
      significance. The main causes of the lumbar pain were sports practice or vigorous
      activities and remaining in a seated position for extended periods of time.

PMID- 27022595
TI  - EVALUATION OF HYPERALGESIA AND HISTOLOGICAL CHANGES OF DORSAL ROOT GANGLION
      INDUCED BY NUCLEUS PULPOSUS.
AB  - To evaluate the hyperalgesia and histological abnormalities induced by contact
      between the dorsal root ganglion and the nucleus pulposus. METHODS: Twenty Wistar
      rats were used, divided into two experimental groups. In one of the groups, a
      fragment of autologous nucleus pulposus was removed from the sacrococcygeal
      region and deposited on the L5 dorsal root ganglia. In the other group (control),
      a fragment of adipose tissue was deposited on the L5 dorsal root ganglia.
      Mechanical and thermal hyperalgesia was evaluated on the third day and the first,
      third, fifth and seventh weeks after the operation. A L5 dorsal root ganglion was
      removed in the first, third, fifth and seventh weeks after the operation for
      histological study using HE staining and histochemical study using specific
      labeling for iNOS. RESULTS: Higher intensity of mechanical and thermal
      hyperalgesia was observed in the group of animals in which the nucleus pulposus
      was placed in contact with the dorsal root ganglion. In this group, the
      histological study showed abnormalities of the dorsal root ganglion tissue,
      characterized by an inflammatory process and axonal degeneration. The
      histopathological abnormalities of the dorsal root ganglion tissue presented
      increasing intensity with increasing length of observation, and there was a
      correlation with maintenance of the hyperalgesia observed in the behavioral
      assessment. Immunohistochemistry using specific labeling for iNOS in the group of
      animals in which the nucleus pulposus was placed in contact with the dorsal root
      ganglion showed higher expression of this enzyme in the nuclei of the
      inflammatory cells (glial cells) surrounding the neurons. CONCLUSION: Contact
      between the nucleus pulposus and the dorsal root ganglion induced mechanical and
      thermal hyperalgesia and caused histological abnormalities in the dorsal root
      ganglion components. These abnormalities were characterized by an inflammatory
      and degenerative process in the structures of the dorsal root ganglion, and they
      presented increasing intensity with longer periods of observation.

PMID- 27022596
TI  - HOW DOES THE BRAZILIAN ORTHOPEDIC SURGEONS TREAT ACUTE LATERAL ANKLE SPRAIN?
AB  - Acute lateral ankle sprain (ALAS) is a common injury, but its treatment has yet
      to be firmly established. The purpose of this study was to investigate how
      Brazilian Orthopedists (including residents) manage the diagnosis,
      classification, treatment and complications of ALAS. METHODS: A multiple-choice
      questionnaire was developed with the aim of addressing the main aspects of the
      treatment of ALAS. The questionnaire was made available on the official website
      of the Brazilian Society of Orthopedics and Traumatology between June 15 and
      August 1, 2004. RESULTS: 444 questionnaires were included in the analysis. The
      results showed agreement among most of the interviewees in the following regards:
      90.8% used a classification method to guide treatment of the sprain; 59%
      classified the ankle sprain with certainty; 63.7% used rigid immobilization in
      cases of totally torn ligaments; 60.6% used anti-inflammatory medication in cases
      of partial ligament tears; and 75.9% reported that residual pain was the most
      frequent complication. There was no consensus regarding the immobilization method
      for partial ALAS, given that immobilization and functional treatment were chosen
      with the same frequency (47%). There was no significant difference between the
      responses from residents and from orthopedists (p = 0.81). CONCLUSIONS:
      Orthopedists and orthopedic residents in Brazil have difficulty classifying ALAS
      and there is no consensus about the best therapeutic option for partial ALAS.

PMID- 27022597
TI  - EPIDEMIOLOGY OF ACETABULUM FRACTURES TREATED AT THE INSTITUTO NACIONAL DE
      TRAUMATOLOGIA E ORTOPEDIA (INTO).
AB  - OBJECTIVES: The purpose of this study was to review the epidemiological aspects
      of displacement fractures of the acetabulum that had been treated surgically at
      the National Institute of Traumatology and Orthopedics (INTO). METHODS: We
      retrospectively analyzed 126 acetabulum fractures that had been treated
      surgically at INTO between March 2006 and November 2008. The following factors
      were taken into account: age, sex, trauma mechanism, injury classification, time
      elapsed between trauma and surgery, affected side and associated bone injuries.
      RESULTS: 76.8% were male; the mean age was 39.6 years. The trauma mechanism was
      traffic accidents in 59%; the time that elapsed between injury and surgery was on
      average 16.4 days; 55% of the cases were on the right side; 30% of the patients
      presented associated fractures. CONCLUSION: Most of the patients were male, in an
      economically active age group, and were victims of traffic accidents. Edge and/or
      posterior column fractures were the most frequent types. Associated injuries were
      common and most of the fractures operated in our service came to us late.

PMID- 27022598
TI  - Newsweek.

PMID- 27022599
TI  - Correction: Trends in relative survival in patients with a diagnosis of
      hepatocellular carcinoma in Ontario: a population-based retrospective cohort
      study.
AB  - [This corrects the article on p. E208 in vol. 3.]. 

PMID- 27022600
TI  - An analytic approach for describing and prioritizing health inequalities at the
      local level in Canada: a descriptive study.
AB  - BACKGROUND: We present the health inequalities analytic approach used by the
      Saskatoon Health Region to examine health equity. Our aim was to develop a method
      that will enable health regions to prioritize action on health inequalities.
      METHODS: Data from admissions to hospital, physician billing, reportable
      diseases, vital statistics and childhood immunizations in the city of Saskatoon
      were analyzed for the years ranging from 1995 to 2011. Data were aggregated to
      the dissemination area level. The Pampalon deprivation index was used as the
      measure of socioeconomic status. We calculated annual rates per 1000 people for
      each outcome. Rate ratios, rate differences, area-level concentration curves and
      area-level concentration coefficients quantified inequality. An Inequalities
      Prioritization Matrix was developed to prioritize action for the outcomes showing
      the greatest inequality. The outcomes measured were cancer, intentional self
      harm, chronic obstructive pulmonary disease, mental illness, heart disease,
      diabetes, injury, stroke, chlamydia, tuberculosis, gonorrhea, hepatitis C, high
      birth weight, low birth weight, teen abortion, teen pregnancy, infant mortality
      and all-cause mortality. RESULTS: According to the Inequalities Prioritization
      Matrix, injuries and chronic obstructive pulmonary disease were the first and
      second priorities, respectively, that needed to be addressed related to
      inequalities in admissions to hospital. For physician billing, mental disorders
      and diabetes were high-priority areas. Differences in teen pregnancy and all
      cause mortality were the most unequal in the vital statistics data. For
      communicable diseases, hepatitis C was the highest priority. INTERPRETATION: Our
      findings show that health inequalities exist at the local level and that a method
      can be developed to prioritize action on these inequalities. Policies should
      consider health inequalities and adopt population-based and targeted actions to
      reduce inequalities.

PMID- 27022601
TI  - Comment on "Transmission Model of Hepatitis B Virus with Migration Effect".
AB  - We show the erroneous assumptions and reasoning by introducing the migration
      effect of individuals in the transmission model of Hepatitis B virus. First, some
      false results related to the eigenvalues and reproductive number in the recent
      literature in mathematical biology will be presented. Then, it will be proved
      that the product of the matrices in the next generation method to obtain the
      reproductive number R 0 is not correct and the local and global stability results
      based on the reproductive number R 0 are considered false. 

PMID- 27022602
TI  - The Effect of Two Different Cognitive Tests on Gait Parameters during Dual Tasks
      in Healthy Postmenopausal Women.
AB  - INTRODUCTION: The paper aims to evaluate the influence of two different demanding
      cognitive tasks on gait parameters using BTS SMART system analysis. PATIENTS AND
      METHODS: The study comprised 53 postmenopausal women aged 64.5 +/- 6.7 years
      (range: 47-79). For every subject, gait analysis using a BTS SMART system was
      performed in a dual-task study design under three conditions: (I) while walking
      only (single task), (II) walking while performing a simultaneous simple cognitive
      task (SCT) (dual task), and (III) walking while performing a simultaneous complex
      cognitive task (CCT) (dual task). Time-space parameters of gait pertaining to the
      length of a single support phase, double support phase, gait speed, step length,
      step width, and leg swing speed were analyzed. RESULTS: Performance of cognitive
      tests during gait resulted in a statistically significant prolongation of the
      left (by 7%) and right (by 7%) foot gait cycle, shortening of the length of steps
      made with the right extremity (by 4%), reduction of speed of swings made with the
      left (by 11%) and right (by 8%) extremity, and reduction in gait speed (by 6%).
      CONCLUSIONS: Performance of cognitive tests during gait changes its individual
      pattern in relation to the level of the difficulty of the task.

PMID- 27022603
TI  - Biochemical and Metabolic Changes in Arsenic Contaminated Boehmeria nivea L.
AB  - Arsenic (As) is identified by the EPA as the third highest toxic inorganic
      contaminant. Almost every 9th or 10th human in more than 70 countries including
      mainland China is affected by As. Arsenic along with other toxins not only
      affects human life but also creates alarming situations such as the deterioration
      of farm lands and desertion of industrial/mining lands. Researchers and
      administrators have agreed to opt for phytoremediation of As over costly
      cleanups. Boehmeria nivea L. can soak up various heavy metals, such as Sb, Cd,
      Pb, and Zn. But the effect of As pollution on the biology and metabolism of B.
      nivea has been somewhat overlooked. This study attempts to evaluate the extent of
      As resistance, chlorophyll content, and metabolic changes in As-polluted (5, 10,
      15, and 20 mg L(-1) As) B. nivea in hydroponics. Toxic effects of As in the form
      of inhibited growth were apparent at the highest level of added As. The
      significant changes in the chlorophyll, electrolyte leakage, and H2O2,
      significant increases in As in plant parts, catalase (CAT), and malondialdehyde
      (MDA), with applied As revealed the potential of B. nivea for As decontamination.
      By employing the metabolic machinery of B. nivea, As was sustainably removed from
      the contaminated areas.

PMID- 27022604
TI  - The Influence of Chronic Illness and Lifestyle Behaviors on Quality of Life among
      Older Thais.
AB  - Chronic conditions and lifestyle behaviors have a detrimental influence on the
      quality of life for seniors because of physical disability and emotional
      concerns. This study aimed to assess the influence of chronic illness, smoking,
      and alcohol use on quality of life among Thai seniors. A cross-sectional study
      was conducted in three communities, selected purposively from the North,
      Northeast, and Central regions, and 1278 senior participants were recruited.
      Binary logistic regression was used to predict the influence of factors on
      quality of life with adjusted covariates. Most participants were aged 60-70 years
      and married, earned 500-1,000 Baht/month (US $17-$35), had one chronic illness,
      and were nonsmokers and nondrinkers. Surprisingly, there appeared to be no link
      between chronic conditions and quality of life. Current drinkers were more likely
      to have a high quality of life, with Odds Ratios of 2.16 for men and 2.73 for
      women. Seniors of both genders who were current drinkers were more likely to
      accept death and dying and this improved their quality of life. Social
      participation in alcohol consumption may encourage seniors to share their
      concerns about death and dying and eventually accept this as a foundation of
      life. 

PMID- 27022605
TI  - Khat Dependency and Psychophysical Symptoms among Chewers in Jazan Region,
      Kingdom of Saudi Arabia.
AB  - BACKGROUND: Khat chewing is highly prevalent in Africa, Yemen and Jazan region,
      southwest of Saudi Arabia. Most of Jazani Khat chewers consider khat session as a
      social activity and do not consider khat dependency. The aim of this study was to
      explore khat dependency and its relationship with the psychophysical symptoms
      among chewers. METHODS: Cross-sectional study on seventy Saudi male khat chewers
      living in Jazan area. Psychological dependence to khat chewing was evaluated
      using the Severity of Dependency Scale (SDS). The participants filled in a self
      administrated assisted structured questionnaire designed to collect data about
      their medical history, neurological symptoms, and their chewing behavior.
      RESULTS: Half (52.2%) of khat chewers showed psychological dependency. Those
      having longer khat sessions (>=6 hours) were more liable for dependency. Physical
      and psychological symptoms were more prevalent among khat dependent chewers.
      CONCLUSIONS: khat has a psychological dependence effect that can be measured by
      the SDS, even in low doses and with irregular use. SDS scale is a useful tool to
      expect the burden of either physical or psychological symptoms on khat chewers.

PMID- 27022606
TI  - Associations of Genetic Variants at Nongenic Susceptibility Loci with Breast
      Cancer Risk and Heterogeneity by Tumor Subtype in Southern Han Chinese Women.
AB  - Current understanding of cancer genomes is mainly "gene centric." However, GWAS
      have identified some nongenic breast cancer susceptibility loci. Validation
      studies showed inconsistent results among different populations. To further
      explore this inconsistency and to investigate associations by intrinsic subtype
      (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han
      Chinese women, we genotyped five nongenic polymorphisms (2q35: rs13387042, 5p12:
      rs981782 and rs4415084, and 8q24: rs1562430 and rs13281615) using MassARRAY IPLEX
      platform in 609 patients and 882 controls. Significant associations with breast
      cancer were observed for rs13387042 and rs4415084 with OR (95% CI) per-allele
      1.29 (1.00-1.66) and 0.83 (0.71-0.97), respectively. In subtype specific
      analysis, rs13387042 (per-allele adjusted OR = 1.36, 95% CI = 1.00-1.87) and
      rs4415084 (per-allele adjusted OR = 0.82, 95% CI = 0.66-1.00) showed slightly
      significant association with Luminal-A subtype; however, only rs13387042 was
      associated with ER-&PR-&HER2+ tumors (per-allele adjusted OR = 1.55, 95% CI =
      1.00-2.40), and none of them were linked to Luminal-B and triple negative
      subtype. Collectively, nongenic SNPs were heterogeneous according to the
      intrinsic subtype. Further studies with larger datasets along with intrinsic
      subtype categorization should explore and confirm the role of these variants in
      increasing breast cancer risk. 

PMID- 27022607
TI  - The Effect of Systemic and Regional Use of Magnesium Sulfate on Postoperative
      Tramadol Consumption in Lumbar Disc Surgery.
AB  - AIM: To investigate the effect of magnesium administered to the operative region
      muscle and administered systemically on postoperative analgesia consumption after
      lumbar disc surgery. MATERIAL AND METHOD: The study included a total of 75 ASA I
      II patients aged 18-65 years. The patients were randomly allocated into 1 of 3
      groups of 25: the Intravenous (IV) Group, the Intramuscular (IM) Group, and the
      Control (C) Group. At the stage of suturing the surgical incision site, the IV
      Group received 50 mg/kg MgSO4 intravenously in 150 mL saline within 30 mins. In
      the IM Group, 50 mg/kg MgSO4 in 30 mL saline was injected intramuscularly into
      the paraspinal muscles. In Group C, 30 mL saline was injected intramuscularly
      into the paraspinal muscles. After operation patients in all 3 groups were given
      100 mg tramadol and 10 mg metoclopramide and tramadol solution was started
      intravenously through a patient-controlled analgesia device. Hemodynamic changes,
      demographic data, duration of anesthesia and surgery, pain scores (NRS), the
      Ramsay sedation score (RSS), the amount of analgesia consumed, nausea- vomiting,
      and potential side effects were recorded. RESULTS: No difference was observed
      between the groups. Nausea and vomiting side effects occurred at a rate of 36% in
      Group C, which was a significantly higher rate compared to the other groups (p <
      0.05). Tramadol consumption in the IM Group was found to be significantly lower
      than in the other groups (p < 0.05). CONCLUSION: Magnesium applied to the
      operative region was found to be more effective on postoperative analgesia than
      systemically administered magnesium.

PMID- 27022608
TI  - X-Ray Scatter Correction on Soft Tissue Images for Portable Cone Beam CT.
AB  - Soft tissue images from portable cone beam computed tomography (CBCT) scanners
      can be used for diagnosis and detection of tumor, cancer, intracerebral
      hemorrhage, and so forth. Due to large field of view, X-ray scattering which is
      the main cause of artifacts degrades image quality, such as cupping artifacts, CT
      number inaccuracy, and low contrast, especially on soft tissue images. In this
      work, we propose the X-ray scatter correction method for improving soft tissue
      images. The X-ray scatter correction scheme to estimate X-ray scatter signals is
      based on the deconvolution technique using the maximum likelihood estimation
      maximization (MLEM) method. The scatter kernels are obtained by simulating the
      PMMA sheet on the Monte Carlo simulation (MCS) software. In the experiment, we
      used the QRM phantom to quantitatively compare with fan-beam CT (FBCT) data in
      terms of CT number values, contrast to noise ratio, cupping artifacts, and low
      contrast detectability. Moreover, the PH3 angiography phantom was also used to
      mimic human soft tissues in the brain. The reconstructed images with our proposed
      scatter correction show significant improvement on image quality. Thus the
      proposed scatter correction technique has high potential to detect soft tissues
      in the brain. 

PMID- 27022609
TI  - Fast 3-Breath-Hold 3-Dimensional Tagging Cardiac Magnetic Resonance in Patients
      with Hypertrophic Myocardial Diseases: A Feasibility Study.
AB  - Tagging CMR has been established as the standard reference for measurement of
      myocardial strain. The current 2D tagging technique requires multiple breath
      holds to cover the whole heart and cannot show the 3D motions of the left
      ventricle. We performed fast 3-breath-hold 3D tagging with localized tagging
      preparation and complementary spatial modulation of magnetization in 10 patients
      with hypertrophic myocardial diseases and 6 normal volunteers. The left wall
      motion was observed at any view angle, which allowed for the identification of
      regional and global hypokinesis using the fast 3D tagging. Although a decrease in
      the circumferential strain and LGE were observed at the basal septum in
      hypertrophic cardiomyopathy, they were not located together in each patient. In
      hypertensive heart disease, the decrease in circumferential strain was observed
      more widely than LGE, and the summed strain of all segments was significantly
      decreased. The decrease in strain and LGE were observed diffusely in cardiac
      amyloidosis. In conclusion, fast 3-breath-hold 3D tagging is feasible for the
      regional and global strain analysis. The location of reduced circumferential
      strain is not necessarily the same as that of LGE and is related to the global
      cardiac function in patients with hypertrophic myocardial diseases. 

PMID- 27022610
TI  - Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical
      Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study.
AB  - BACKGROUND: Delayed union and nonunion are common complications in atypical
      femoral fractures (AFFs) despite having good fracture fixation. Demineralized
      bone matrix (DBM) is a successfully proven method for enhancing fracture healing
      of the long bone fracture and nonunion and should be used in AFFs. This study
      aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs) fixation with
      and without DBM. MATERIALS AND METHODS: A prospective study was conducted on 9 ST
      AFFs patients using DBM (DBM group) during 2013-2014 and compared with a
      retrospective consecutive case series of ST-AFFs patients treated without DBM
      (2010-2012) (NDBM group, 9 patients). All patients were treated with the same
      standard guideline and followed up until fractures completely united.
      Postoperative outcomes were then compared. RESULTS: DBM group showed a
      significant shorter healing time than NDBM group (28.1 +/- 14.4 versus 57.9 +/-
      36.8 weeks, p = 0.04). Delayed union was found in 4 patients (44%) in DBM group
      compared with 7 patients (78%) in NDBM group (p > 0.05). No statistical
      difference of nonunion was demonstrated between both groups (DBM = 1 and NDBM =
      2, p > 0.05). Neither postoperative infection nor severe local tissue reaction
      was found. CONCLUSIONS: DBM is safe and effective for accelerating the fracture
      healing in ST-AFFx and possibly reduces nonunion after fracture fixation. Trial
      registration number is TCTR20151021001.

PMID- 27022611
TI  - The Correlation of Serum Myeloid-Related Protein-8/14 and Eosinophil Cationic
      Protein in Patients with Coronary Artery Disease.
AB  - OBJECTIVE: To investigate the changes in serum Myeloid-Related Protein 8/14
      (MRP8/14) and Eosinophil Cationic Protein (ECP) levels in patients with different
      types of coronary artery diseases (CAD) and assess the value of MRP8/14 and ECP
      detection in predicting CAD. METHODS: 178 patients were divided into CAD group
      including unstable angina pectoris (UAP), acute myocardial infarction (AMI), and
      stable angina pectoris (SAP). Thirty-six individuals with normal coronary artery
      served as the control group. Serum MRP8/14 and ECP were measured by ELISA. The
      severity of coronary artery stenosis was assessed by the numbers of involved
      coronary artery branches and the sum of Gensini scores. RESULTS: The MRP8/14
      levels were significantly higher in AMI and UAP group than SAP and control group
      (P < 0.05). The levels of MRP8/14 in AMI group were also obviously higher than
      UAP group (P < 0.05). The ECP levels were obviously increased in AMI group, but
      there was no difference between SAP and UAP group (P > 0.05). The ECP was
      significantly increased in three impaired coronary arteries and obviously
      correlated with Gensini score (P < 0.01), whereas the MRP8/14 was obviously
      positively correlated with CRP (P < 0.01). CONCLUSIONS: Increased MRP8/14 levels
      suggest the instability of the atherosclerotic plaque. ECP reflects the severity
      of coronary arteries stenosis, predicting atherosclerosis burden. They may become
      the new biomarkers of CAD.

PMID- 27022612
TI  - Integrated Multipoint-Laser Endoscopic Airway Measurements by Transoral Approach.
AB  - OBJECTIVES: Optical and technical characteristics usually do not allow objective
      endoscopic distance measurements. So far no standardized method for endoscopic
      distance measurement is available. The aim of this study was to evaluate the
      feasibility and accuracy of transoral airway measurements with a multipoint-laser
      endoscope. METHODS: The semirigid endoscope includes a multipoint laser
      measurement system that projects 49 laser points (wavelength 639 nm, power < 5
      mW) into the optical axis of the endoscopic view. Distances, areas, and depths
      can be measured in real-time. Transoral endoscopic airway measurements were
      performed on nine human cadavers, which were correlated with CT measurements.
      RESULTS: The preliminary experiment showed an optimum distance between the
      endoscope tip and the object of 5 to 6 cm. There was a mean measurement error of
      3.26% +/- 2.53%. A Spearman correlation coefficient of 0.95 (p = 0.01) was
      calculated for the laryngeal measurements and of 0.93 (p < 0.01) for the tracheal
      measurements compared to the CT. Using the Bland-Altman-Plot, the 95% limits of
      agreement for the laryngeal measurements were satisfactory: -0.76 and 0.93.
      CONCLUSIONS: Integrated multipoint-laser endoscopic measurement is a promising
      technical supplement, with potential use in diagnostic endoscopy and transoral
      endoscopic surgery in daily practice.

PMID- 27022613
TI  - Does the Gadoxetic Acid-Enhanced Liver MRI Impact on the Treatment of Patients
      with Colorectal Cancer? Comparison Study with 18F-FDG PET/CT.
AB  - OBJECTIVES: We evaluated the value of Gadoxetic acid-enhanced liver MRI in the
      preoperative staging of colorectal cancer and estimated the clinical impact of
      liver MRI in the management plan of liver metastasis. METHODS: We identified 108
      patients who underwent PET/CT and liver MRI as preoperative evaluation of
      colorectal cancer, between January 2011 and December 2013. We evaluated the per
      nodule sensitivity of PET/CT and liver MRI for liver metastasis. Management plan
      changes were estimated for patients with metastatic nodules newly detected on
      liver MRI, to assess the clinical impact. RESULTS: We enrolled 131 metastatic
      nodules (mean size 1.6 cm) in 41 patients (mean age 65 years). The per nodule
      sensitivities of PET/CT and liver MRI were both 100% for nodules measuring 2 cm
      or larger but were significantly different for nodules measuring less than 2 cm
      (59.8% and 95.1%, resp., P = 0.0001). At least one more metastatic nodule was
      detected on MRI in 16 patients. Among these, 7 patients indicated changes of
      management plan after performing MRI. CONCLUSIONS: Gadoxetic acid-enhanced liver
      MRI detected more metastatic nodules compared with PET/CT, especially for small
      (<2 cm) nodules. The newly detected nodules induced management plan change in
      43.8% (7/16) of patients.

PMID- 27022614
TI  - Diffusion-Weighted Imaging of Small Peritoneal Implants in "Potentially" Early
      Stage Ovarian Cancer.
AB  - INTRODUCTION: MRI is established modality for the diagnosis of ovarian
      malignancies. Advances in MRI technology, including DW imaging, could lead to the
      further increase in the sensitivity of MRI for the detection of peritoneal
      metastases. The aim of this study was to assess the accuracy of DW imaging for
      detection of peritoneal metastatic disease in patients suspected of having
      potentially early ovarian cancer and secondly to evaluate ADC values of
      peritoneal implants. MATERIALS AND METHODS: The prospective study group consisted
      of 26 women with sonographic or/and CT diagnosis of suspected ovarian tumor.
      Based on the results of the above imaging, in none of them was extraovarian
      spread of disease or ascites recognized. All patients underwent MRI with DW
      imaging. RESULTS: Overall, 18 extraovarian peritoneal lesions were found on DW
      images in 10 from 26 examined patients. All implants had diameter <=10 mm. The
      presence of all lesions diagnosed by MRI was confirmed intraoperatively.
      Histopathologic findings in 17 proofs confirmed ovarian cancer. PPV was 94%. On
      all DW images (with b values of 0, 50, 100, 150, 200, 400, 800, and 1200 s/mm(2))
      the mean signal intensities of peritoneal lesions were significantly higher than
      the mean signal intensities of normal adjacent tissue (p = 0.000001).

PMID- 27022615
TI  - A Study of Using Massage Therapy Accompanied with Stretching Exercise for
      Rehabilitation of Mammary Gland Hyperplasia.
AB  - PURPOSE: To apply massage therapy accompanied with stretching exercises for
      treatment of mammary gland hyperplasia, evaluate the clinical outcome in
      patients, and estimate the therapy as a novel treatment method for mammary
      hyperplasia. METHODS: 28 adult female patients were selected and treated with
      massage therapy and stretching exercises focusing on skeleton muscles of chest,
      abdomen, and axilla. The mammary gland oxyhemoglobin (OxyHb) and deoxyhemoglobin
      (DeoxyHb) levels were detected before and after treatment after 15, 30, and 45
      days. RESULTS: In this cohort, pretreatment OxyHb (mean +/- SD) is 1.32 +/- 0.14
      (medium-high), and DeoxyHb is 0.87 +/- 0.13 (normal). All patients were
      clinically diagnosed with benign mammary gland hyperplasia and mastitis. The
      posttreatment OxyHb levels are 1.23 +/- 0.09 (normal-medium, 15-day), 1.16 +/-
      0.08 (normal, 30-day), and 1.05 +/- 0.04 (normal, 45-day), and DeoxyHb levels are
      0.90 +/- 0.11 (normal, 15-day), 0.94 +/- 0.18 (normal, 30-day), and 0.98 +/- 0.12
      (normal, 45-day). Patients were diagnosed with decreased hyperplasia 15 and 30
      days after treatment and with no symptom of hyperplasia in mammary gland 45 days
      after treatment. CONCLUSION: Mammary gland hyperplasia is closely correlated with
      pathological changes of skeletal muscles and could be significantly improved by
      massage therapy and stretching exercises targeting neighboring skeletal muscles.

PMID- 27022617
TI  - Compressed Sensing/Sparse-Recovery Approach for Improved Range Resolution in
      Narrow-Band Radar.
AB  - A compressed sensing/sparse-recovery procedure is adopted to obtain enhanced
      range resolution capability from the processing of data acquired with narrow-band
      SFCW radars. A mathematical formulation for the proposed approach is reported and
      validity limitations are fully discussed, by demonstrating the ability to
      identify a great number of targets, up to 20, in the range direction. Both
      numerical and experimental validations are presented, by assuming also noise
      conditions. The proposed method can be usefully applied for the accurate
      detection of parameters with very small variations, such as those involved in the
      monitoring of soil deformations or biological objects. 

PMID- 27022616
TI  - Jedi Public Health: Co-creating an Identity-Safe Culture to Promote Health
      Equity.
AB  - The extent to which socially-assigned and culturally mediated social identity
      affects health depends on contingencies of social identity that vary across and
      within populations in day-to-day life. These contingencies are structurally
      rooted and health damaging inasmuch as they activate physiological stress
      responses. They also have adverse effects on cognition and emotion, undermining
      self-confidence and diminishing academic performance. This impact reduces
      opportunities for social mobility, while ensuring those who "beat the odds" pay a
      physical price for their positive efforts. Recent applications of social identity
      theory toward closing racial, ethnic, and gender academic achievement gaps
      through changing features of educational settings, rather than individual
      students, have proved fruitful. We sought to integrate this evidence with growing
      social epidemiological evidence that structurally-rooted biopsychosocial
      processes have population health effects. We explicate an emergent framework,
      Jedi Public Health (JPH). JPH focuses on changing features of settings in
      everyday life, rather than individuals, to promote population health equity, a
      high priority, yet, elusive national public health objective. We call for an
      expansion and, in some ways, a re-orienting of efforts to eliminate population
      health inequity. Policies and interventions to remove and replace discrediting
      cues in everyday settings hold promise for disrupting the repeated physiological
      stress process activation that fuels population health inequities with
      potentially wide application.

PMID- 27022618
TI  - How Muscle Structure and Composition Influence Meat and Flesh Quality.
AB  - Skeletal muscle consists of several tissues, such as muscle fibers and connective
      and adipose tissues. This review aims to describe the features of these various
      muscle components and their relationships with the technological, nutritional,
      and sensory properties of meat/flesh from different livestock and fish species.
      Thus, the contractile and metabolic types, size and number of muscle fibers, the
      content, composition and distribution of the connective tissue, and the content
      and lipid composition of intramuscular fat play a role in the determination of
      meat/flesh appearance, color, tenderness, juiciness, flavor, and technological
      value. Interestingly, the biochemical and structural characteristics of muscle
      fibers, intramuscular connective tissue, and intramuscular fat appear to play
      independent role, which suggests that the properties of these various muscle
      components can be independently modulated by genetics or environmental factors to
      achieve production efficiency and improve meat/flesh quality. 

PMID- 27022619
TI  - Neuron Morphology Influences Axon Initial Segment Plasticity.
AB  - In most vertebrate neurons, action potentials are initiated in the axon initial
      segment (AIS), a specialized region of the axon containing a high density of
      voltage-gated sodium and potassium channels. It has recently been proposed that
      neurons use plasticity of AIS length and/or location to regulate their intrinsic
      excitability. Here we quantify the impact of neuron morphology on AIS plasticity
      using computational models of simplified and realistic somatodendritic
      morphologies. In small neurons (e.g., dentate granule neurons), excitability was
      highest when the AIS was of intermediate length and located adjacent to the soma.
      Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were
      most excitable when the AIS was longer and/or located away from the soma. For any
      given somatodendritic morphology, increasing dendritic membrane capacitance
      and/or conductance favored a longer and more distally located AIS. Overall,
      changes to AIS length, with corresponding changes in total sodium conductance,
      were far more effective in regulating neuron excitability than were changes in
      AIS location, while dendritic capacitance had a larger impact on AIS performance
      than did dendritic conductance. The somatodendritic influence on AIS performance
      reflects modest soma-to-AIS voltage attenuation combined with neuron size
      dependent changes in AIS input resistance, effective membrane time constant, and
      isolation from somatodendritic capacitance. We conclude that the impact of AIS
      plasticity on neuron excitability will depend largely on somatodendritic
      morphology, and that, in some neurons, a shorter or more distally located AIS may
      promote, rather than limit, action potential generation. 

PMID- 27022621
TI  - No Evidence for Sex Differences in the Electrophysiological Properties and
      Excitatory Synaptic Input onto Nucleus Accumbens Shell Medium Spiny Neurons.
AB  - Sex differences exist in how the brain regulates motivated behavior and reward,
      both in normal and pathological contexts. Investigations into the underlying
      neural mechanisms have targeted the striatal brain regions, including the dorsal
      striatum and nucleus accumbens core and shell. These investigations yield
      accumulating evidence of sexually different electrophysiological properties,
      excitatory synaptic input, and sensitivity to neuromodulator/hormone action in
      select striatal regions both before and after puberty. It is unknown whether the
      electrical properties of neurons in the nucleus accumbens shell differ by sex,
      and whether sex differences in excitatory synaptic input are present before
      puberty. To test the hypothesis that these properties differ by sex, we performed
      whole-cell patch-clamp recordings on male and female medium spiny neurons (MSNs)
      in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We
      analyzed passive and active electrophysiological properties, and miniature EPSCs
      (mEPSCs). No sex differences were detected; this includes those properties, such
      as intrinsic excitability, action potential afterhyperpolarization, threshold,
      and mEPSC frequency, that have been found to differ by sex in other striatal
      regions and/or developmental periods. These findings indicate that, unlike other
      striatal brain regions, the electrophysiological properties of nucleus accumbens
      shell MSNs do not differ by sex. Overall, it appears that sex differences in
      striatal function, including motivated behavior and reward, are likely mediated
      by other factors and striatal regions. 

PMID- 27022620
TI  - Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection
      Following Traumatic Brain Injury.
AB  - Type-1 interferons (IFNs) are pleiotropic cytokines that signal through the type
      1 IFN receptor (IFNAR1). Recent literature has implicated the type-1 IFNs in
      disorders of the CNS. In this study, we have investigated the role of type-1 IFNs
      in neuroinflammation following traumatic brain injury (TBI). Using a controlled
      cortical impact model, TBI was induced in 8- to 10-week-old male C57BL/6J WT and
      IFNAR1(-/-) mice and brains were excised to study infarct volume, inflammatory
      mediator release via quantitative PCR analysis and immune cell profile via
      immunohistochemistry. IFNAR1(-/-) mice displayed smaller infarcts compared with
      WT mice after TBI. IFNAR1(-/-) mice exhibited an altered anti-inflammatory
      environment compared with WT mice, with significantly reduced levels of the
      proinflammatory mediators TNFalpha, IL-1beta and IL-6, an up-regulation of the
      anti-inflammatory mediator IL-10 and an increased activation of resident and
      peripheral immune cells after TBI. WT mice injected intravenously with an anti
      IFNAR1 blocking monoclonal antibody (MAR1) 1 h before, 30 min after or 30 min and
      2 d after TBI displayed significantly improved histological and behavioral
      outcome. Bone marrow chimeras demonstrated that the hematopoietic cells are a
      peripheral source of type-1 IFNs that drives neuroinflammation and a worsened TBI
      outcome. Type-1 IFN mRNA levels were confirmed to be significantly altered in
      human postmortem TBI brains. Together, these data demonstrate that type-1 IFN
      signaling is a critical pathway in the progression of neuroinflammation and
      presents a viable therapeutic target for the treatment of TBI. 

PMID- 27022622
TI  - Kruppel-Like Factor 4 (KLF4) Is Not Required for Retinal Cell Differentiation.
AB  - During early vertebrate eye development, a regulatory network of transcription
      factors regulates retinal cell differentiation and survival into adulthood. Among
      those factors, Kruppel-like factor 4 (KLF4) plays the dual role of maintaining
      the stem cell status of retinal progenitors cells and repressing the intrinsic
      axon regeneration ability in retinal ganglion cells (RGCs) after injury. This
      study further investigated whether KLF4 plays a role in early retinal cell
      differentiation or survival into adulthood. We examined different types of
      retinal neurons, including RGCs, amacrine cells, bipolar cells, Muller cells, and
      photoreceptor cells, in adult mice in which KLF4 was conditionally deleted in
      early retinal development using Chx10-promoted Cre by immunohistochemistry. We
      compared the numbers of retinal neurons and the thickness of photoreceptor and
      nerve fiber layers between Chx10-Cre-driven KLF4 deletion mice and wild-type
      mice. There was no significant difference in cell number among any of the retinal
      cell types or in photoreceptor layer thickness with KLF4 deletion during early
      development. The thickness of axon bundles in the nerve fiber layer in the Chx10
      conditional KLF4 knock-out mice was greater than that in wild-type mice. These
      results suggest that KLF4 is not required for retinal cell differentiation or
      survival, but does normally limit retinal ganglion cell axon bundle thickness.
      These data support a hypothesis that KLF4 suppresses axon growth during
      development. 

PMID- 27022623
TI  - Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced
      ATM Signaling.
AB  - Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the
      ATM (A-T mutated) gene. It strikes before 5 years of age and leads to
      dysfunctions in many tissues, including the CNS, where it leads to
      neurodegeneration, primarily in cerebellum. Alzheimer's disease (AD), by
      contrast, is a largely sporadic neurodegenerative disorder that rarely strikes
      before the 7th decade of life with primary neuronal losses in hippocampus,
      frontal cortex, and certain subcortical nuclei. Despite these differences, we
      present data supporting the hypothesis that a failure of ATM signaling is
      involved in the neuronal death in individuals with AD. In both, partially ATM
      deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In
      human AD, three independent indices of reduced ATM function-nuclear translocation
      of histone deacetylase 4, trimethylation of histone H3, and the presence of cell
      cycle activity-appear coordinately in neurons in regions where degeneration is
      prevalent. These same neurons also show reduced ATM protein levels. And though
      they represent only a fraction of the total neurons in each affected region,
      their numbers significantly correlate with disease stage. This previously unknown
      role for the ATM kinase in AD pathogenesis suggests that the failure of ATM
      function may be an important contributor to the death of neurons in AD
      individuals. 

PMID- 27022624
TI  - Long-Latency Feedback Coordinates Upper-Limb and Hand Muscles during Object
      Manipulation Tasks.
AB  - Suppose that someone bumps into your arm at a party while you are holding a glass
      of wine. Motion of the disturbed arm will engage rapid and goal-directed feedback
      responses in the upper-limb. Although such responses can rapidly counter the
      perturbation, it is also clearly desirable not to destabilize your grasp and/or
      spill the wine. Here we investigated how healthy humans maintain a stable grasp
      following perturbations by using a paradigm that requires spatial tuning of the
      motor response dependent on the location of a virtual target. Our results
      highlight a synchronized expression of target-directed feedback in shoulder and
      hand muscles occurring at ~60 ms. Considering that conduction delays are longer
      for the more distal hand muscles, these results suggest that target-directed
      responses in hand muscles were initiated before those for the shoulder muscles.
      These results show that long-latency feedback can coordinate upper limb and hand
      muscles during object manipulation tasks. 

PMID- 27022625
TI  - Touch Perception Altered by Chronic Pain and by Opioid Blockade.
AB  - Touch plays a significant role in human social behavior and social communication,
      and its rewarding nature has been suggested to involve opioids. Opioid blockade
      in monkeys leads to increased solicitation and receipt of grooming, suggesting
      heightened enjoyment of touch. We sought to study the role of endogenous opioids
      in perception of affective touch in healthy adults and in patients with
      fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor
      availability. The pleasantness of touch has been linked to the activation of C
      tactile fibers, which respond maximally to slow gentle touch and correlate with
      ratings of pleasantness. We administered naloxone to patients and healthy
      controls to directly observe the consequences of u-opioid blockade on the
      perceived pleasantness and intensity of touch. We found that at baseline chronic
      pain patients showed a blunted distinction between slow and fast brushing for
      both intensity and pleasantness, suggesting reduced C-tactile touch processing.
      In addition, we found a differential effect of opioid blockade on touch
      perception in healthy subjects and pain patients. In healthy individuals, opioid
      blockade showed a trend toward increased ratings of touch pleasantness, while in
      chronic pain patients it significantly decreased ratings of touch intensity.
      Further, in healthy individuals, naloxone-induced increase in touch pleasantness
      was associated with naloxone-induced decreased preference for slow touch,
      suggesting a possible effect of opioid levels on processing of C-tactile fiber
      input. These findings suggest a role for endogenous opioids in touch processing,
      and provide further evidence for altered opioid functioning in chronic pain
      patients. 

PMID- 27022626
TI  - Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and
      Neuropathic Pain.
AB  - We report a novel transgenic mouse model in which the terminals of peripheral
      nociceptors can be silenced optogenetically with high spatiotemporal precision,
      leading to the alleviation of inflammatory and neuropathic pain. Inhibitory
      archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8(+) primary
      afferents using the Nav1.8-Cre driver line. Arch expression covered both
      peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably
      blocked electrically induced action potentials in DRG neurons. Acute transdermal
      illumination of the hindpaws of Nav1.8-Arch(+) mice significantly reduced
      mechanical allodynia under inflammatory conditions, while basal mechanical
      sensitivity was not affected by the optical stimulation. Arch-driven
      hyperpolarization of nociceptive terminals was sufficient to prevent
      channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in
      double-transgenic Nav1.8-ChR2(+)-Arch(+) mice. Furthermore, prolonged optical
      silencing of peripheral afferents in anesthetized Nav1.8-Arch(+) mice led to
      poststimulation analgesia with a significant decrease in mechanical and thermal
      hypersensitivity under inflammatory and neuropathic conditions. These findings
      highlight the role of peripheral neuronal inputs in the onset and maintenance of
      pain hypersensitivity, demonstrate the plasticity of pain pathways even after
      sensitization has occurred, and support the involvement of Nav1.8(+) afferents in
      both inflammatory and neuropathic pain. Together, we present a selective
      analgesic approach in which genetically identified subsets of peripheral sensory
      fibers can be remotely and optically inhibited with high temporal resolution,
      overcoming the compensatory limitations of genetic ablations. 

PMID- 27022627
TI  - CA3 Synaptic Silencing Attenuates Kainic Acid-Induced Seizures and Hippocampal
      Network Oscillations.
AB  - Epilepsy is a neurological disorder defined by the presence of seizure activity,
      manifest both behaviorally and as abnormal activity in neuronal networks. An
      established model to study the disorder in rodents is the systemic injection of
      kainic acid, an excitatory neurotoxin that at low doses quickly induces
      behavioral and electrophysiological seizures. Although the CA3 region of the
      hippocampus has been suggested to be crucial for kainic acid-induced seizure,
      because of its strong expression of kainate glutamate receptors and its high
      degree of recurrent connectivity, the precise role of excitatory transmission in
      CA3 in the generation of seizure and the accompanying increase in neuronal
      oscillations remains largely untested. Here we use transgenic mice in which CA3
      pyramidal cell synaptic transmission can be inducibly silenced in the adult to
      demonstrate CA3 excitatory output is required for both the generation of
      epileptiform oscillatory activity and the progression of behavioral seizures. 

PMID- 27022628
TI  - Normal Performance of Fmr1 Mice on a Touchscreen Delayed Nonmatching to Position
      Working Memory Task.
AB  - Fragile X syndrome is a neurodevelopmental disorder characterized by mild-to
      severe cognitive deficits. The complete absence of Fmr1 and its protein product
      in the mouse model of fragile X (Fmr1 KO) provides construct validity. A major
      conundrum in the field is the remarkably normal performance of Fmr1 mice on
      cognitive tests in most reports. One explanation may be insufficiently
      challenging cognitive testing procedures. Here we developed a delayed nonmatching
      to position touchscreen task to test the hypothesis that paradigms placing
      demands on working memory would reveal robust and replicable cognitive deficits
      in the Fmr1 KO mouse. We first tested Fmr1 KO mice (Fmr1) and their wild-type
      (WT) littermates in a simple visual discrimination task, followed by assessment
      of reversal learning. We then tested Fmr1 and WT mice in a new touchscreen
      nonmatch to position task and subsequently challenged their working memory
      abilities by adding delays, representing a higher cognitive load. The performance
      by Fmr1 KO mice was equal to WTs on both touchscreen tasks. Last, we replicated
      previous reports of normal performance by Fmr1 mice on Morris water maze spatial
      navigation and reversal. These results indicate that, while the Fmr1 mouse model
      effectively recapitulates many molecular and cellular aspects of fragile X
      syndrome, the cognitive profile of Fmr1 mice generally does not recapitulate the
      primary cognitive deficits in the human syndrome, even when diverse and
      challenging tasks are imposed. 

PMID- 27022629
TI  - Targeted Deletion of Vesicular GABA Transporter from Retinal Horizontal Cells
      Eliminates Feedback Modulation of Photoreceptor Calcium Channels.
AB  - The cellular mechanisms underlying feedback signaling from horizontal cells to
      photoreceptors, which are important for the formation of receptive field
      surrounds of early visual neurons, remain unsettled. Mammalian horizontal cells
      express a complement of synaptic proteins that are necessary and sufficient for
      calcium-dependent exocytosis of inhibitory neurotransmitters at their contacts
      with photoreceptor terminals, suggesting that they are capable of releasing GABA
      via vesicular release. To test whether horizontal cell vesicular release is
      involved in feedback signaling, we perturbed inhibitory neurotransmission in
      these cells by targeted deletion of the vesicular GABA transporter (VGAT), the
      protein responsible for the uptake of inhibitory transmitter by synaptic
      vesicles. To manipulate horizontal cells selectively, an iCre mouse line with Cre
      recombinase expression controlled by connexin57 (Cx57) regulatory elements was
      generated. In Cx57-iCre mouse retina, only horizontal cells expressed Cre
      protein, and its expression occurred in all retinal regions. After crossing with
      a VGAT(flox/flox) mouse line, VGAT was selectively eliminated from horizontal
      cells, which was confirmed immunohistochemically. Voltage-gated ion channel
      currents in horizontal cells of Cx57-VGAT(-/-) mice were the same as Cx57
      VGAT(+/+) controls, as were the cell responses to the ionotropic glutamate
      receptor agonist kainate, but the response to the GABAA receptor agonist muscimol
      in Cx57-VGAT(-/-) mice was larger. In contrast, the feedback inhibition of
      photoreceptor calcium channels, which in control animals is induced by horizontal
      cell depolarization, was completely absent in Cx57-VGAT(-/-) mice. The results
      suggest that vesicular release of GABA from horizontal cells is required for
      feedback inhibition of photoreceptors. 

PMID- 27022630
TI  - Rab3-GEF Controls Active Zone Development at the Drosophila Neuromuscular
      Junction.
AB  - Synaptic signaling involves the release of neurotransmitter from presynaptic
      active zones (AZs). Proteins that regulate vesicle exocytosis cluster at AZs,
      composing the cytomatrix at the active zone (CAZ). At the Drosophila
      neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of
      CAZ proteins across release sites, thereby regulating the efficacy of individual
      AZs. Here we identify Rab3-GEF as a second protein that acts in conjunction with
      Rab3 to control AZ protein composition. At rab3-GEF mutant NMJs, Bruchpilot (Brp)
      and Ca(2+) channels are enriched at a subset of AZs, leaving the remaining sites
      devoid of key CAZ components in a manner that is indistinguishable from rab3
      mutant NMJs. As the Drosophila homologue of mammalian DENN/MADD and
      Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor
      (GEF) for Rab3 that stimulates GDP to GTP exchange. Mechanistic studies reveal
      that although Rab3 and Rab3-GEF act within the same mechanism to control AZ
      development, Rab3-GEF is involved in multiple roles. We show that Rab3-GEF is
      required for transport of Rab3. However, the synaptic phenotype in the rab3-GEF
      mutant cannot be fully explained by defective transport and loss of GEF activity.
      A transgenically expressed GTP-locked variant of Rab3 accumulates at the NMJ at
      wild-type levels and fully rescues the rab3 mutant but is unable to rescue the
      rab3-GEF mutant. Our results suggest that although Rab3-GEF acts upstream of Rab3
      to control Rab3 localization and likely GTP-binding, it also acts downstream to
      regulate CAZ development, potentially as a Rab3 effector at the synapse. 

PMID- 27022633
TI  - Editorial: Randomised controlled trials of factorial design alias on how to speed
      up research on effectiveness of interventions without compromising its validity.

PMID- 27022631
TI  - Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin
      Antagonist-Mediated REM Sleep.
AB  - Hypocretin 1 and 2 (Hcrts; also known as orexin A and B), excitatory
      neuropeptides synthesized in cells located in the tuberal hypothalamus, play a
      central role in the control of arousal. Hcrt inputs to the locus coeruleus
      norepinephrine (LC NE) system and the posterior hypothalamic histaminergic
      tuberomammillary nuclei (TMN HA) are important efferent pathways for Hcrt-induced
      wakefulness. The LC expresses Hcrt receptor 1 (HcrtR1), whereas HcrtR2 is found
      in the TMN. Although the dual Hcrt/orexin receptor antagonist almorexant (ALM)
      decreases wakefulness and increases NREM and REM sleep time, the neural circuitry
      that mediates these effects is currently unknown. To test the hypothesis that ALM
      induces sleep by selectively disfacilitating subcortical wake-promoting
      populations, we ablated LC NE neurons (LCx) or TMN HA neurons (TMNx) in rats
      using cell-type-specific saporin conjugates and evaluated sleep/wake following
      treatment with ALM and the GABAA receptor modulator zolpidem (ZOL). Both LCx and
      TMNx attenuated the promotion of REM sleep by ALM without affecting ALM-mediated
      increases in NREM sleep. Thus, eliminating either HcrtR1 signaling in the LC or
      HcrtR2 signaling in the TMN yields similar effects on ALM-induced REM sleep
      without affecting NREM sleep time. In contrast, neither lesion altered ZOL
      efficacy on any measure of sleep-wake regulation. These results contrast with
      those of a previous study in which ablation of basal forebrain cholinergic
      neurons attenuated ALM-induced increases in NREM sleep time without affecting REM
      sleep, indicating that Hcrt neurotransmission influences distinct aspects of NREM
      and REM sleep at different locations in the sleep-wake regulatory network. 

PMID- 27022634
TI  - Bone augmentation at implant dehiscences and fenestrations. A systematic review
      of randomised controlled trials.
AB  - PURPOSE: To evaluate the efficacy of the bone augmentation procedure at
      dehiscence or fenestration defects in one-stage implant insertion and to evaluate
      which is the most effective procedure. MATERIALS AND METHODS: A systematic review
      of articles selected from MEDLINE, Cochrane Central Register of Controlled Trials
      (CENTRAL) and Google Scholar was performed. Additional studies handsearched and
      found in printed versions of the principal dental implant journals were included.
      Only randomised controlled trials (RCTs) were included. Outcome variables
      considered were implant failure, complications, aesthetic and functional
      satisfaction, complete fill of the defect, clinical and radiological bone level
      variation, and vestibular peri-implant recession. Independent data extraction by
      two authors using predefined data fields, including study quality indicators, was
      completed. All pooled analyses were based on random effects models. RESULTS: A
      total of 65 full-text articles were examined in detail. Forty-six of the 65
      articles did not meet the inclusion criteria. Nineteen articles involving 15
      trials were identified for inclusion in the review. Only one study was considered
      to be at a low risk of bias. The included studies involved 396 patients and 535
      implants. Comparing the test group using membranes with the control without
      membranes, a statistically significant difference was obtained for vertical
      variation of the peri-implant defect; the difference was 1.64 mm (three RCTs, 95%
      CI from 0.47 to 2.80 mm; P = 0.006, I2 = 0%) favouring the use of a membrane. Non
      resorbable polytetrafluoroethylene (ePTFE) membranes obtained a complete clinical
      fill of defects more frequently than resorbable polylactide/polyglycolide (PLGA)
      membranes. The odds ratio was 0.15 (two RCTs, 95% CI from 0.04 to 0.64 mm; P =
      0.01, I2 = 0%), favouring the use of ePTFE membranes. No differences were
      observed comparing nonresorbable ePTFE membranes and resorbable collagen
      membranes. The comparison between crosslinked membranes and collagen native
      membranes yielded a very high heterogeneity for vertical variation of the peri
      implant defect (two RCTs, I2 = 91%, P = 0.001). Dehiscence complications were
      more frequent using cross-linked membranes but the odds ratio was not significant
      (three RCTs, odds ratio 0.44, 95% CI from 0.18 to 1.10; P = 0.08, I2 = 4%).
      CONCLUSIONS: Overall, the evidence is not sufficiently robust to determine if any
      treatment is needed and which is the best treatment for dehiscence or
      fenestration defects at one-stage implant placement. Only 15 trials were included
      and the majority are of limited sample size, have short follow-ups as well as
      having a high risk of bias. The use of a membrane can contribute to the
      regeneration of the hard tissue in horizontal one-stage augmentation. The
      complete fill of the defect was obtained more frequently when a non-resorbable
      ePTFE membrane was used compared to a resorbable PLGA membrane. No differences
      were observed comparing non-resorbable ePTFE membranes and resorbable collagen
      membranes. No substantial differences were obtained using different non
      resorbable membranes and grafts, and the results were positive for the variables
      examined. A high result of heterogeneity was observed in studies dealing with
      cross-linked membranes.

PMID- 27022632
TI  - Specific Targeting of the Basolateral Amygdala to Projectionally Defined
      Pyramidal Neurons in Prelimbic and Infralimbic Cortex.
AB  - Adjacent prelimbic (PL) and infralimbic (IL) regions in the medial prefrontal
      cortex have distinct roles in emotional learning. A complete mechanistic
      understanding underlying this dichotomy remains unclear. Here we explored
      targeting of specific PL and IL neurons by the basolateral amygdala (BLA), a
      limbic structure pivotal in pain and fear processing. In mice, we used retrograde
      labeling, brain-slice recordings, and adenoviral optogenetics to dissect
      connectivity of ascending BLA input onto PL and IL neurons projecting to the
      periaqueductal gray (PAG) or the amygdala. We found differential targeting of BLA
      projections to PL and IL cortex. Activating BLA projections evoked excitatory and
      inhibitory responses in cortico-PAG (CP) neurons in layer 5 (L5) of both PL and
      IL cortex. However, all inhibitory responses were polysynaptic and monosynaptic
      BLA input was stronger to CP neurons in IL cortex. Conversely, the BLA
      preferentially targeted corticoamygdalar (CA) neurons in layer 2 (L2) of PL over
      IL cortex. We also reveal that BLA input is projection specific by showing
      preferential targeting of L5 CP neurons over neighboring L3/5 CA neurons in IL
      cortex. We conclude by showing that BLA input is laminar-specific by producing
      stronger excitatory responses CA neurons in L3/5 compared with L2 in IL cortex.
      Collectively, this study reveals differential targeting of the BLA to PL and IL
      cortex, which depends both on laminar location and projection target of cortical
      neurons. Overall, our findings should have important implications for
      understanding the processing of pain and fear input by the PL and IL cortex. 

PMID- 27022635
TI  - Posterior jaws rehabilitated with partial prostheses supported by 4.0 x 4.0 mm or
      by longer implants: One-year post-loading results from a multicenter randomised
      controlled trial.
AB  - PURPOSE: To evaluate whether 4.0 x 4.0 mm dental implants could be an alternative
      to implants at least 8.5 mm long, which were placed in posterior jaws, in the
      presence of adequate bone volumes. MATERIALS AND METHODS: One hundred and fifty
      patients with posterior (premolar and molar areas) jaws having at least 12.5 mm
      bone height above the mandibular canal or 11.5 mm below the maxillary sinus, were
      randomised according to a parallel group design, in order to receive one to three
      4.0 mm-long implants or one to three implants which were at least 8.5 mm-long, at
      three centres. All implants had a diameter of 4.0 mm. Implants were loaded after
      4 months with definitive screw-retained prostheses. Patients were followed up to
      1-year post-loading and outcome measures were prosthesis and implant failures,
      any complications and peri-implant marginal bone level changes. RESULTS: Seventy
      five patients were randomly allocated to each group. One patient dropped out
      after the 4-month post-loading evaluation from the long implant group. Up to 1
      year post-loading, 3 patients lost one 4.0 mm-long implant each in comparison to
      2 patients who lost one long implant each (difference in proportion = 0.013; 95%
      CI: -0.058 to 0.087; P = 0.506). All failures occurred before loading, the failed
      implants were replaced and the delivery of two prostheses in each group was
      delayed for several months (difference in proportion = 0.0004; 95% CI: -0.068 to
      0.069; P = 0.685). Three short implant patients experienced three complications
      versus 2 long implant patients (difference in proportion = 0.013; 95% CI: -0.058
      to 0.087; P = 0.506). There were no statistically significant differences in
      prosthesis failures, implant failures and complications. Patients with short
      implants lost on average 0.53 mm of peri-implant bone and patients with longer
      implants lost 0.57 mm. There were no statistically significant differences in
      bone level changes up to 1 year between short and long implants (mean difference
      = 0.038 mm; 95% CI: -0.068 to 0.138; P = 0.198). CONCLUSIONS: One year after
      loading 4.0 mm-long implants achieved similar results as 8.5 mm-long or longer
      implants in posterior jaws, however 5- to 10-year post-loading data are necessary
      before reliable recommendations can be made.

PMID- 27022636
TI  - Immediate occluding definitive partial fixed prosthesis versus non-occluding
      provisional restorations - 4-month post-loading results from a pragmatic
      multicenter randomised controlled trial.
AB  - PURPOSE: To compare the clinical outcome of dental implants restored with
      definitive occluding partial fixed prostheses within 1 week, after implant
      placement with immediate non-occluding provisional restorations, which were to be
      replaced by definitive prostheses after 4 months. MATERIALS AND METHODS: Fifty
      partially edentulous patients treated with one to three dental implants, at least
      8.5 mm long and 4.0 mm wide inserted with a torque of at least 35 Ncm, were
      randomised in two groups of 25 patients each, to be immediately loaded with
      partial fixed prostheses. Patients of one group received one definitive screw
      retained metal-ceramic prosthesis in occlusion within 1 week after placement.
      Patients of the other group received one non-occluding provisional acrylic
      reinforced prosthesis within 24 h after implant placement. Provisional prostheses
      were replaced after 4 months by definitive ones. The follow-up for all patients
      was 4-months post-loading. Outcome measures were prosthesis and implant failures,
      any complications, peri-implant marginal bone level changes, aesthetic evaluation
      by a clinician, patient satisfaction, chair time and number of visits at the
      dental office from implant placement to delivery of definitive restorations.
      RESULTS: No patient dropped out. Two immediately occlusally loaded implants with
      their related definitive prostheses (8%) failed early (difference in proportions
      = 0.08; 95% CI: -0.03 to 0.19; P = 0.490). Four complications occurred in the
      occlusal group versus one in the non-occlusal group; (difference in proportions =
      0.12; 95% CI: -0.04 to 0.28; P = 0.349). Four months after loading, patients
      subjected to non-occlusal loading lost an average of 0.72 mm of peri-implant bone
      versus 0.99 mm of patients restored with occluding definitive partial fixed
      prostheses. There were no statistically significant differences for marginal bone
      level changes between the two groups (mean difference = -0.27 mm; 95% CI: -0.84
      to 0.30; P = 0.349). The differences for aesthetic scores showed no statistical
      significance (8.26 versus 7.58; P = 0.445); the same was seen for aesthetics
      evaluated by patients (Mann-Whitney U test: P = 0.618). Patients in the non
      occlusal group were significantly more satisfied with the function of their
      implant-supported prostheses (Mann-Whitney U test: P = 0.039). Significantly less
      chair time (mean difference = -28.4 min; 95% CI: -48.82 to -7.99; P = 0.007) and
      the number of visits (mean difference = -1.88; 95% CI: -2.43 to -1.33; P < 0.001)
      were required for the immediate definitive prosthesis group. CONCLUSION: This
      study did not provide a conclusive answer but may suggest that provisional
      prostheses non-occlusally immediately loaded may increase patient functional
      satisfaction, chair time and the number of visits, with respect to definitive
      prostheses immediately loaded in functional occlusion.

PMID- 27022637
TI  - A low dose of subperiosteal anaesthesia injection versus a high dose of
      infiltration anaesthesia to minimise the risk of nerve damage at implant
      placement: A randomised controlled trial.
AB  - PURPOSE: To evaluate whether a low-dose subperiosteal anaesthesia is effective in
      minimising risks of inferior alveolar nerve damage at implant placement when
      compared to high-dose infiltration anaesthesia. MATERIAL AND METHODS: One hundred
      and twenty patients requiring the placement of a single implant in order to
      replace a missing first mandibular were randomly allocated to two groups: group A
      (awake hemilip) subperiosteal crestal injection equal to 0.9 ml of articaine with
      0.5% epinephrine and group B (numb hemilip) infiltration equal to 7.2 ml of
      articaine with 0.5% epinephrine in the vestibular fundus. Intraoperative sensory
      control using sensory tests was carried out in all patients. Outcome measures
      were neurological complications, intraoperative and postoperative visual analogue
      scale (VAS) scores for pain and swelling, and a questionnaire evaluating patient
      satisfaction. Patients were followed for 1 week postoperatively. RESULTS: There
      were no cases of nerve injury. Seven days after surgery the postoperative VAS
      score for pain and swelling was lower in group A in a statistically significant
      manner (difference = -3.41%; 95% CI: -5.57, -1.26; P = 0.002 and difference = 
      3.33%; 95% CI: -5.41, -1.25; P = 0.002, respectively). CONCLUSIONS: No nerve
      damage occurred using either anaesthesia types, therefore the choice of type of
      anaesthesia is a subjective clinical decision, however it may be preferable to
      use a low dose (0.9 ml) of subperiosteal anaesthesia, since it is unnecessary to
      deliver 7.2 ml of articaine to anaesthetise a single mandibular molar implant
      site.

PMID- 27022638
TI  - Immediate loading of bimaxillary total fixed prostheses supported by five
      flapless-placed implants with machined surfaces: A 6-month follow-up prospective
      single cohort study.
AB  - PURPOSE: To evaluate the clinical outcome of fully edentulous patients
      rehabilitated with immediately loaded bimaxillary screw-retained metal-resin
      prostheses supported by five implants placed flapless: two in the mandible and
      three in the maxillae. MATERIALS AND METHODS: Twenty-five consecutively treated
      patients were recruited. To be immediately loaded, implants had to be inserted
      with a minimum torque of 80 Ncm. Outcome measures were prosthesis and implant
      failures, and complications. RESULTS: Six months after loading no patients
      dropped out and no prosthesis or implant failed. Two maxillary prostheses were
      loaded early at 8 weeks because implants were inserted with a torque inferior to
      45 Ncm. Three complications occurred in two patients but they were all
      successfully treated. CONCLUSIONS: Six months after loading, immediately loaded
      bimaxillary cross-arch prostheses can be supported by only two mandibular and
      three maxillary flapless-placed dental implants. Longer follow-ups of
      approximately 10 years are needed to understand the prognosis of this treatment
      modality.

PMID- 27022639
TI  - Is a high level of total cholesterol a risk factor for dental implants or bone
      grafting failure? A retrospective cohort study on 227 patients.
AB  - PURPOSE: This study aims to verify the effect of hypercholeresterolaemia on
      implant and bone augmentation failures. MATERIALS AND METHODS: A retrospective
      cohort study was conducted on 268 sequential patients scheduled for implant and
      bone augmentation surgery under conscious sedation in a private practice. Total
      serum cholesterol (TC) levels were assessed via blood tests before surgery.
      Patients were divided into two groups: TC < 200 mg/dl and TC > 200 mg/dl. A 6
      month post-loading follow-up was scheduled both for implants and grafts. The
      outcomes considered were implant failure (removal) and graft infection/failure.
      The effect of cholesterol on early implant and grafting failure was investigated
      according to a logistic regression model. RESULTS: Two hundred and twenty-seven
      patients fulfilled inclusion criteria; 139 had hypercholesterolemia. The 6-month
      post-loading overall implant failure rate was 6.25% at patient level (2.00% at
      implant level). Partial or total graft infection rate was 10.2%. High TC
      increased by 7.48 times the odds of the grafting failure (P = 0.047; 95% CI: 
      0.94 to 59.23), whilst it did not modify the odds of implant failure (P = 0.749;
      95% CI: 0.28 to 2.49). CONCLUSIONS: High total serum cholesterol levels tend to
      increase graft failure rates whilst it did not influence implant failures.

PMID- 27022640
TI  - Outcome of dental implants in diabetic patients with and without cardiovascular
      disease: A 5-year post-loading retrospective study.
AB  - PURPOSE: To investigate the outcome of immediate function of dental implant
      rehabilitations in diabetic patients with and without coexisting cardiovascular
      diseases (CVD). MATERIALS AND METHODS: This retrospective study included 70
      diabetic patients (33 females and 37 males, average age: 59 years old),
      rehabilitated with 352 implants and divided into two groups (CVD: 38 patients;
      non-CVD: 32 patients). Diabetes mellitus was defined as fasting plasma glucose >=
      7.0 mmol/l (126 mg/dl) or 2 h plasma glucose >= 11.1mmol/l (200 mg/dl). The data
      was retrieved from patient records. Primary outcome measures were prosthesis and
      implant survival; secondary outcome measures were marginal bone loss and
      complications (biological or mechanical). The follow-up was 5 years after loading
      for all patients. RESULTS: Seven patients (10%) were lost to follow-up (one
      patient in the CVD group; and six patients in the non-CVD group). One prosthesis
      failed in the non-CVD group, rendering a 97.4% survival rate, compared to 100% in
      the CVD group (non-significant difference between groups; P = 0.359). Ten
      implants failed in 7 patients: CVD group with eight implant failures in 5
      patients (86.7% cumulative survival rate) versus two implants in 2 patients in
      the non-CVD group (93.8% cumulative survival rate) with a non-significant
      difference between both groups (P = 0.365). The average (95% confidence interval)
      marginal bone loss at 1- and 5-years was 0.95 mm (0.66 mm; 1.23 mm) and 1.52 mm
      (1.20 mm; 1.88 mm), respectively in the CVD group; and 0.78 mm (0.40 mm; 1.16 mm)
      and 1.54 mm (0.86 mm; 2.31 mm), respectively for the non-CVD group; with no
      significant differences between groups at 1 year (P = 0.979) and 5 years (P =
      0.300). Complications occurred in 38 patients (CVD group: 21 patients; non-CVD
      group: 16 patients); with a non-significant difference between both groups (P =
      0.660). CONCLUSIONS: Implant rehabilitations represent a valid treatment for
      diabetic patients with or without coexisting CVD, with a good risk/benefit ratio.

PMID- 27022642
TI  - Effects of 4-META/MMA-TBB Resin at Different Curing Stages on Osteoblasts and
      Gingival Epithelial Cells.
AB  - PURPOSE: To assess the effects of different curing stages of 4-META/MMA-TBB resin
      on osteoblasts and gingival keratinocytes. MATERIALS AND METHODS: The MC3T3-E1
      murine pre-osteoblastic cell line and GE-1 murine gingival epithelial cell line
      were cultured with mixtures of Super-Bond C&B at different curing stages, and the
      cell viability was assessed. The alkaline phosphatase (ALP) activity of the MC3T3
      E1 cells was also assessed. RESULTS: The majority of the MC3T3-E1 cells died and
      showed no ALP activity when cultured with 4-META/MMA-TBB resin during the initial
      curing phase (1 min of curing). A later curing phase of the 4-META/MMA-TBB resin
      (7 min of curing) showed cytotoxicity at day 1, but the toxic effect was
      temporary and the proliferative capacity and ALP activity in the cells were
      similar to control cells at day 7. Completely cured 4-META/MMA-TBB resin (after 1
      or 12 h of curing) did not affect the cell viability or ALP activity of the MC3T3
      E1 cells. In contrast, 4-META/MMA-TBB resin showed no effect on the GE-1 cells at
      any stage of curing. CONCLUSION: Although 4-META/MMA-TBB resin during the initial
      curing phase shows toxic effects on MC3T3-E1 cells, that cytotoxicity is minimal
      at later curing phases. In contrast, neither the uncured nor cured resins
      affected the GE-1 cells.

PMID- 27022643
TI  - Resistance of Hydraulic Calcium Silicate Cements to Dislodgment in Short- and
      Long-term Assessment.
AB  - PURPOSE: To investigate the resistance to dislodgment produced by Biodentine
      (Septodont) and White-MTA (Angelus) after immersion in phosphate-buffered saline
      (PBS) for different durations. MATERIALS AND METHODS: Dentin disks 1 +/- 0.1 mm
      thick were obtained from the middle third of the roots of 6 human maxillary
      canines. On the coronal surface of each dentin disk, four 0.8-mm-diameter holes
      were drilled. Then the slices were halved using a low-speed saw diamond disk, and
      the two holes in each half were filled with one of the two tested materials. Each
      filled half was immersed in PBS solution (pH 7.2) either for 7 days (short term)
      or 60 days (long term) at 37 degrees C. The push-out test was performed after
      both time periods. A general linear model (GLM) for repeated measures ANOVA was
      used to verify the effect of the material and duration of contact with PBS on the
      push-out strength. The material was considered as the within-subject contrast and
      the contact duration as the between-subjects effect (p < 0.05). RESULTS: Repeated
      measures GLM indicated a significant impact of material and time on the push-out
      strength of the samples (p = 0.000 and p = 0.033, respectively). Biodentine
      significantly improved the push-out strength compared to MTA at both times (p =
      0.000). The lack of significance in the interaction between material and time
      indicates that PBS immersion positively influenced the push-out values of both
      tested materials. CONCLUSION: Long-term PBS immersion positively influenced the
      resistance to dislodgement from dentin of all cements tested. The Biodentine
      cement provided greater resistance to push-out force than did the MTA.

PMID- 27022644
TI  - Effects of Different Radiation Doses on the Bond Strengths of Two Different
      Adhesive Systems to Enamel and Dentin.
AB  - PURPOSE: To evaluate the effects of three different radiation doses on the bond
      strengths of two different adhesive systems to enamel and dentin. MATERIALS AND
      METHODS: Eighty human third molars were randomly divided into four groups (n =
      20) according to the radiation dose (control/no radiation, 20 Gy, 40 Gy, and 70
      Gy). The teeth were sagittally sectioned into three slices: one mesial and one
      distal section containing enamel and one middle section containing dentin. The
      sections were then placed in the enamel and dentin groups, which were further
      divided into two subgroups (n = 10) according to the adhesive used. Three
      restorations were performed in each tooth (one per section) using Adper Single
      Bond 2 (3M ESPE) or Universal Single Bond (3M ESPE) adhesive system and Filtek
      Z350 XT (3M ESPE) resin composite and subjected to the microshear bond test. Data
      were analyzed using a two-way ANOVA followed by Tukey's test. Failure modes were
      examined under a stereoscopic loupe. RESULTS: Radiotherapy did not affect the
      bond strengths of the adhesives to either enamel or dentin. In dentin, the
      Universal Single Bond adhesive system showed higher bond strength values when
      compared with the Adper Single Bond adhesive system. More adhesive failures were
      observed in the enamel for all radiation doses and adhesives. CONCLUSION:
      Radiotherapy did not influence the bond strength to enamel or dentin,
      irrespective of the adhesive or radiation dose used.

PMID- 27022645
TI  - Influence of Light Irradiation Through Zirconia on the Degree of Conversion of
      Composite Cements.
AB  - PURPOSE: To assess the light irradiance (LI) delivered by two light-curing units
      and to measure the degree of conversion (DC) of three composite cements and one
      flowable composite when cured through zirconia or ceramic-veneered zirconia
      plates with different thicknesses. MATERIALS AND METHODS: Three dual-curing
      composite cements (Clearfil Esthetic Cement, Panavia F2.0, G-CEM LinkAce) and one
      light-curing flowable composite (G-aenial Universal Flo) were investigated. Nine
      different kinds of zirconia plates were prepared from three zirconia grades (YSZ:
      Aadva and KATANA; Ce-TZP/Al2O3: NANOZR) in three different thicknesses (0.5- and
      1.5-mm-thick zirconia, and 0.5-mm-thick zirconia veneered with a 1.0-mm-thick
      veneering ceramic). Portions of the mixed composite cements and the flowable
      composite were placed on a light spectrometer to measure LI while being light
      cured through the zirconia plates for 40 s using two light-curing units (n = 5).
      After light curing, micro-Raman spectra of the composite films were acquired to
      determine DC at 5 and 10 min, 1 and 24 h, and at 1 week. RESULTS: The zirconia
      grade and the thickness of the zirconia/veneered zirconia plates significantly
      decreased LI. Increased LI did not increase DC. Only the Ce-TZP/Al2O3 (NANOZR)
      zirconia was too opaque to allow sufficient light transmission and resulted in
      significantly lower DC. CONCLUSION: Although zirconia-based restorations
      attenuate the LI of light-curing units, the composite cements and the flowable
      composite could be light cured through the YSZ zirconia. LI is too low through Ce
      TZP/Al2O3 zirconia, necessitating the use of self-/dual-curing composite cements.

PMID- 27022646
TI  - Editorial: Can chronic pain develop following routine dental treatment ?

PMID- 27022647
TI  - Etiology and pathogenesis of dental erosion.
AB  - The condition of dental erosion is defined as acid-related loss of tooth
      structure which does not involve microorganisms. Depending on the origin of the
      acid, extrinsic (usually caused by acids in food) and intrinsic (caused by
      endogenous acid) erosion can be distinguished. The presence and severity of
      erosive defects depend on various parameters such as nutrition, saliva, general
      diseases, and mechanical stress by abrasion and attrition. As an example, dietary
      habits which involve frequent intake of acidic food and beverages, occupational
      acid exposure, as well as certain drugs or diseases that affect saliva flow rate
      are accompanied by an increased risk of erosive dental hard tissue defects. By a
      thorough clinical examination and an accurate anamnesis, various erosion-related
      risk factors can be identified and strategies to reduce or eliminate these
      factors be identified. 

PMID- 27022648
TI  - Double hydrophosphination of alkynes promoted by rhodium: the key role of an N
      heterocyclic carbene ligand.
AB  - The regioselective double hydrophosphination of alkynes mediated by rhodium
      catalysts is presented. The distinctive stereoelectronic properties of the NHC
      ligand prevent the catalyst deactivation by diphosphine coordination thereby
      allowing for the closing of a productive catalytic cycle. 

PMID- 27022649
TI  - [Not Available].

PMID- 27022650
TI  - Withdrawal of 'An Expression of Concern: Organization of connections of the basal
      and accessory basal nuclei in the monkey amygdala'.

PMID- 27022651
TI  - [Not Available].

PMID- 27022652
TI  - [Not Available].

PMID- 27022653
TI  - [Not Available].

PMID- 27022654
TI  - [Problems of dental services in closed administrative units assessed by a survey
      of dentists].
AB  - The article presents the results of the survey of 150 dentists from 10 closed
      administrative units of FMBA health care system of Russia in connection with the
      dynamics of dental staff withdrawal and reduce of volume of preventive work in
      schools and factories. These problems were found to be associated with the lack
      of regulations on mandatory preventive dental examinations of workers with
      occupational hazards, low tariffs for dental services in obligatory medical
      insurance program, poor wages an lack of apartments for young dentists.

PMID- 27022655
TI  - Ischemic conditions and beta-secretase activation: The impact of membrane
      cholesterol enrichment as triggering factor in rat brain endothelial cells.
AB  - Among harmful conditions damaging the blood-brain barrier, cerebral stroke and
      reperfusion injuries were proposed as contributing factors to Alzheimer's disease
      etiology. Indeed it was reported that ischemic conditions promote beta-amyloid
      peptide production in brain endothelial cells, although implicated mechanisms are
      yet not fully understood.Oxidative injury related to ischemia affects membrane
      lipids profile by altering their biochemical properties and structural dynamics,
      which are also believed to play significant role in the amyloid precursor protein
      processing, suggesting a link between alterations in lipid membrane composition
      and beta-amyloid peptide production enhancement.Using brain microvascular
      endothelial cells, here we demonstrate how oxygen and glucose deprivation
      followed by normal conditions restoration, mimicking ischemic environment,
      increases cell cholesterol amount (+20%), reduces membrane fluidity and results
      in strong activation (+40%) of beta-secretase 1 enzymatic activity. Moreover, we
      observed an increase of amyloid precursor protein and beta-secretase 1 protein
      levels with altered localization in non-discrete (Triton X-100 soluble) membrane
      domains, leading to an enhanced production of amyloid precursor protein beta
      carboxyl-terminal fragment. Therefore, lipid alterations induced by oxygen and
      glucose deprivation enhance beta-secretase 1 activity, favor its proximity to
      amyloid precursor protein and may concur to increased amyloidogenic cleavage. The
      latter, represents a detrimental event that may contribute to beta-amyloid
      homeostasis impairment in the brain and to Alzheimer's disease-related BBB
      dysfunctions.

PMID- 27022656
TI  - The loss of MiR-139-5p promotes colitis-associated tumorigenesis by mediating
      PI3K/AKT/Wnt signaling.
AB  - MiR-139-5p down-regulation has frequently been implicated in colorectal
      carcinoma. However, there is little known about its biological function between
      inflammation and cancer in vivo. Here, a transgenic murine model of colorectal
      carcinoma was used to investigate pathogenetic role of miR-139-5p in colitis and
      colitis-associated tumorigenesis. We showed that miR-139-5p knockout mice were
      higher sensitive to DSS-induced colitis and enhanced formation of intestinal
      neoplasia was observed when mice were exposed to AOM/DSS treatment. MiR-139-5p
      knockout mice exhibited an increased expression of genes involved in Wnt pathway.
      Such genes are closely associated with cell proliferation and differentiation,
      promoting the beta-catenin nuclear accumulation. Furthermore, biochemical studies
      in HCT-116 cells revealed that the over-expression of miR-139-5p inhibited the
      crosstalk between PI3K/AKT and Wnt pathway mediated by IGF-1R. Collectively,
      these findings indicate that miR-139-5p plays a crucial role in the development
      and progression of colitis-associated tumorigenesis and suggest that miR-139-5p
      may serve as a potential therapeutic target for the treatment of colitis
      associated cancer in the future.

PMID- 27022657
TI  - [Hypertension and cognitive impairments: Possible mechanism of development,
      diagnosis, and approaches to therapy].
AB  - The review presents data on the role of hypertension in the development of
      cognitive impairments. It discusses issues of the early diagnosis of
      hypertension, the possibility of an integrated approach to therapy for cognitive
      disorders in hypertensive patients.

PMID- 27022658
TI  - [Unsolved problems of cytoprotective therapy in patients with coronary heart
      disease].
AB  - The paper gives data on the proven efficiency of myocardial cytoprotection with
      the pFOX inhibitors trimetazidine and meldonium for coronary heart disease.
      However, no algorithm has been defined for their differentiated use at different
      ischemic remodeling stages in these patients in terms of the mechanism of
      metabolic effects. Sequential use of meldonium and trimetazidine in different
      periods of acute and chronic myocardial ischemia may become one of the possible
      ways to increase the efficacy of the pFOX inhibitors.

PMID- 27022659
TI  - [Current optimization of combined therapy for chronic obstructive pulmonary
      disease].
AB  - Testing the new combined bronchodilator Anoro Ellipta in different clinical
      trials gives to its high clinical efficacy and safety in chronic obstructive
      pulmonary disease. The drug contains the molecules of sustained-release selective
      beta2-adrenergic receptor agonist (vilanterol) and a muscarinic cholinergic
      receptor antagonist (umeclidinium bromide). The bronchodilating mechanisms of
      umeclidinium bromide are in the competitive inhibition of the binding of
      acetylcholine with muscarinic acetylcholine receptors of airway smooth muscles
      whereas in those of vilanterol are in that with the stimulation of intracellular
      adenylate cyclase. On days 1 and 24 after inhalation of the first dose of
      vilanterol and umeclidinium bromide, there was a significant increase in the
      forced expiratory volume in one second as compared to placebo. No clinical
      effects on QT interval on an electrocardiogram and cardiac rhythm were found. The
      benefits of an inhalation device (Ellipta) are its innovation design ensuring the
      effective delivery of an aerosol dose into the airway, convenience, and
      simplicity.

PMID- 27022660
TI  - [Ophthalmologic manifestation of granulomatosis with polyangiitis (Wegener's
      granulomatosis)].
AB  - Granulomatosis with polyangiitis (GPA), formerly earlier known as Wegener's
      granulomatosis, is primary system necrotizing vasculitis of small and medium
      sized vessels, which is characterized by the formation of foci of granulomatous
      inflammation. One of the target organs in GPA is the organ of vision. Its
      affection may not only reduce quality of life, but also may lead to the severest
      complications even to fatal outcome. The affection varies in severity from slight
      inflammation of the ocular superficial structures to severe involvement of all
      orbital and ocular structures to develop complete blindness, including bilateral
      one. GPA can affect any portion of the organ of vision. The changes are low
      specific, which makes early diagnosis and timely adequate therapy difficult.
      Overall all ophthalmologic manifestations can be divide into 4 groups: 1) lesions
      of the orbit and appendages; 2) those of the conjunctiva and fibrous tunic of the
      eyeball: 3) those of the retina: 4) those of the optic nerve. Orbital affection
      is characterized by the development of granulomas, dacryoadenitis with marked
      inflammatory infiltration of the surrounding tissues, including oculomotor
      muscles, and destruction of orbital bony walls. Nonspecific conjunctivitis and
      episcleritis are commonly encountered. Affection of the fibrous tunic of the
      eyeball is characterized by the development of necrotizing scleritis, peripheral
      ulcerative or stromal keratitis. The retina is rarely involved and mainly
      described as sporadic cases in the literature. The optic nerve is most commonly
      damaged due to the compression of the orbit by inflamed tissue; the lesion is
      more infrequently ischemic.

PMID- 27022661
TI  - Correction in author list.
AB  - [This corrects the article on p. 414 in vol. 9, PMID: 26788231.]. 

PMID- 27022662
TI  - Role of Microstructure and Surface Defects on the Dissolution Kinetics of CeO2, a
      UO2 Fuel Analogue.
AB  - The release of radionuclides from spent fuel in a geological disposal facility is
      controlled by the surface mediated dissolution of UO2 in groundwater. In this
      study we investigate the influence of reactive surface sites on the dissolution
      of a synthesized CeO2 analogue for UO2 fuel. Dissolution was performed on the
      following: CeO2 annealed at high temperature, which eliminated intrinsic surface
      defects (point defects and dislocations); CeO2-x annealed in inert and reducing
      atmospheres to induce oxygen vacancy defects and on crushed CeO2 particles of
      different size fractions. BET surface area measurements were used as an indicator
      of reactive surface site concentration. Cerium stoichiometry, determined using X
      ray Photoelectron Spectroscopy (XPS) and supported by X-ray Diffraction (XRD)
      analysis, was used to determine oxygen vacancy concentration. Upon dissolution in
      nitric acid medium at 90  degrees C, a quantifiable relationship was established
      between the concentration of high energy surface sites and CeO2 dissolution rate;
      the greater the proportion of intrinsic defects and oxygen vacancies, the higher
      the dissolution rate. Dissolution of oxygen vacancy-containing CeO2-x gave rise
      to rates that were an order of magnitude greater than for CeO2 with fewer oxygen
      vacancies. While enhanced solubility of Ce(3+) influenced the dissolution, it was
      shown that replacement of vacancy sites by oxygen significantly affected the
      dissolution mechanism due to changes in the lattice volume and strain upon
      dissolution and concurrent grain boundary decohesion. These results highlight the
      significant influence of defect sites and grain boundaries on the dissolution
      kinetics of UO2 fuel analogues and reduce uncertainty in the long term
      performance of spent fuel in geological disposal.

PMID- 27022663
TI  - Potential Energy Surfaces for the First Two Lowest-Lying Electronic States of the
      LiH2(+) System, and Dynamics of the H(+) + LiH ? H2(+) + Li + Reactions.
AB  - Two new potential energy surfaces are established for the ground and first
      excited electronic states of the LiH2(+) system, which are important for the
      astrophysics-related H(+) + LiH(+) and H(+) + LiH reactions. The ab initio energy
      points are calculated using the complete active space self-consistent field and
      multireference configuration interaction method with aug-cc-pVQZ basis set. At
      each state, more than 40000 energy points are calculated. The spectroscopic
      constants of the diatoms and the topographical characters of the new surfaces are
      examined in detail, showing good agreement with the available literature results.
      The reaction probabilities, integral and differential cross sections, and rate
      constants for the H(+) + LiH ? H2(+) + Li reactions are obtained by performing
      quantum dynamics calculations, and compared with the previous literature results.
      The reaction mechanisms are discussed in detail. It is shown that the new
      surfaces can be recommended for the dynamics study of the H(+) + LiH(+) and H(+)
      + LiH(+) reactions and other research including LiH2(+) based rovibrational
      spectra and cluster dynamics. 

PMID- 27022664
TI  - Hyaluronidase To Enhance Nanoparticle-Based Photodynamic Tumor Therapy.
AB  - Photodynamic therapy (PDT) is considered as a safe and selective way to treat a
      wide range of cancers as well as nononcological disorders. However, as oxygen is
      required in the process of PDT, the hypoxic tumor microenvironment has largely
      limited the efficacy of PDT to treat tumors especially those with relatively
      large sizes. To this end, we uncover that hyaluronidase (HAase), which breaks
      down hyaluronan, a major component of extracellular matrix (ECM) in tumors, would
      be able to enhance the efficacy of nanoparticle-based PDT for in vivo cancer
      treatment. It is found that the administration of HAase would lead to the
      increase of tumor vessel densities and effective vascular areas, resulting in
      increased perfusion inside the tumor. As a result, the tumor uptake of
      nanomicelles covalently linked with chlorine e6 (NM-Ce6) would be increased by ~2
      folds due to the improved "enhanced permeability and retention" (EPR) effect,
      while the tumor oxygenation level also shows a remarkable increase, effectively
      relieving the hypoxia state inside the tumor. Those effects taken together offer
      significant benefits in greatly improving the efficacy of PDT delivered by
      nanoparticles. Taking advantage of the effective migration of HAase from the
      primary tumor to its drainage sentinel lymph nodes (SLNs), we further demonstrate
      that this strategy would be helpful to the treatment of metastatic lymph nodes by
      nanoparticle-based PDT. Lastly, both enhanced EPR effect of NM-Ce6 and relieved
      hypoxia state of tumor are also observed after systemic injection of modified
      HAase, proving its potential for clinical translation. Therefore, our work
      presents a new concept to improve the efficacy of nanomedicine by modulating the
      tumor microenvironment. 

PMID- 27022665
TI  - Folding Behaviors of Protein (Lysozyme) Confined in Polyelectrolyte Complex
      Micelle.
AB  - The folding/unfolding behavior of proteins (enzymes) in confined space is
      important for their properties and functions, but such a behavior remains largely
      unexplored. In this article, we reported our finding that lysozyme and a double
      hydrophilic block copolymer, methoxypoly(ethylene glycol)5K-block-poly(l-aspartic
      acid sodium salt)10 (mPEG(5K)-b-PLD10), can form a polyelectrolyte complex
      micelle with a particle size of ~30 nm, as verified by dynamic light scattering
      and transmission electron microscopy. The unfolding and refolding behaviors of
      lysozyme molecules in the presence of the copolymer were studied by
      microcalorimetry and circular dichroism spectroscopy. Upon complex formation with
      mPEG(5K)-b-PLD10, lysozyme changed from its initial native state to a new
      partially unfolded state. Compared with its native state, this copolymer
      complexed new folding state of lysozyme has different secondary and tertiary
      structures, a decreased thermostability, and significantly altered
      unfolding/refolding behaviors. It was found that the native lysozyme exhibited
      reversible unfolding and refolding upon heating and subsequent cooling, while
      lysozyme in the new folding state (complexed with the oppositely charged PLD
      segments of the polymer) could unfold upon heating but could not refold upon
      subsequent cooling. By employing the heating-cooling-reheating procedure, the
      prevention of complex formation between lysozyme and polymer due to the salt
      screening effect was observed, and the resulting uncomplexed lysozyme regained
      its proper unfolding and refolding abilities upon heating and subsequent cooling.
      Besides, we also pointed out the important role the length of the PLD segment
      played during the formation of micelles and the monodispersity of the formed
      micelles. Furthermore, the lysozyme-mPEG(5K)-b-PLD10 mixtures prepared in this
      work were all transparent, without the formation of large aggregates or
      precipitates in solution as frequently observed in other protein-polyelectrolyte
      systems. Hence, the present protein-PEGylated poly(amino acid) mixture provides
      an ideal water-soluble model system to study the important role of electrostatic
      interaction in the complexation between proteins and polymers, leading to
      important new knowledge on the protein-polymer interactions. Moreover, the
      polyelectrolyte complex micelle formed between protein and PEGylated polymer may
      provide a good drug delivery vehicle for therapeutic proteins.

PMID- 27022666
TI  - Use of Nitrogen Isotope To Determine Fertilizer- and Soil-Derived Ammonia
      Volatilization in a Rice/Wheat Rotation System.
AB  - The nitrogen (N) isotope method reveals that application of fertilizer N can
      increase crop uptake or denitrification and leaching losses of native soil N via
      the "added N interaction". However, there is currently little evidence of the
      impact of added N on soil N losses through NH3 volatilization using (15)N
      methodologies. In the present study, a three-year rice/wheat rotated experiment
      with 30% (15)N-labeled urea applied in the first rice season and unlabeled urea
      added in the following five crop seasons was performed to investigate
      volatilization of NH3 from fertilizer and soil N. We found 9.28% of NH3 loss from
      (15)N urea and 2.88-7.70% declines in (15)N-NH3 abundance occurred during the
      first rice season, whereas 0.11% of NH3 loss from (15)N urea and 0.02-0.21%
      enrichments in (15)N-NH3 abundance happened in the subsequent seasons. The
      contributions of fertilizer- and soil-derived N to NH3 volatilization from a
      rice/wheat rotation were 75.8-88.4 and 11.6-24.2%, respectively. These distinct
      variations in (15)N-NH3 and substantial soil-derived NH3 suggest that added N
      clearly interacts with the soil source contributing to NH3 volatilization. 

PMID- 27022667
TI  - Hydroalcoholic extract of Myrtus communis can alter anxiety and sleep parameters:
      a behavioural and EEG sleep pattern study in mice and rats.
AB  - CONTEXT: Myrtus communis L. (Myrtaceae), myrtle, is an evergreen shrub with
      strong antibacterial, anti-inflammatory, antihyperglycemic and antioxidant
      activities. Also, it is used as a sedative-hypnotic plant in Iranian traditional
      medicine. OBJECTIVE: This study evaluates the effect of 80% ethanolic extract of
      M. communis leaves on sleep and anxiety in mice and rats. MATERIALS AND METHODS:
      Male NMRI mice were subjected to open field, righting reflex, grip strength and
      pentylentetrazole-induced seizure tests. Male Wistar rats were used to evaluate
      the alterations in rapid eye movement (REM) and non-REM (NREM) sleep. They were
      treated with 25-400 mg/kg doses of the extract intraperitoneally. RESULTS: The
      applied doses (50-200 mg/kg) of M. communis extract increased vertical (ED50 =
      40.2 +/- 6.6 mg/kg) and vertical and horizontal activity (ED50 = 251 +/- 55
      mg/kg), while treatment with 200 and 400 mg/kg attenuated muscle tone
      significantly compared to vehicle treated animals (p < 0.001 for all) in a dose
      independent manner. Also, a significant hypnotic and not anticonvulsant effect
      was observed when animals were treated with 200 mg/kg of the extract (p < 0.01).
      In this regard, electroencephalography results showed that REM sleep time was
      decreased (2.4 +/- 0.5%), while total and NREM sleep times were increased
      significantly compared to the control group of mice (82.5 +/- 7.6%). DISCUSSION
      AND CONCLUSION: The data show the anxiolytic and muscle relaxant effect of the
      extract without anticonvulsant activities. The anxiolytic, myorelaxant and
      hypnotic effects without effect on seizure threshold are in line with the effect
      of a alpha 2 GABA receptor agonist.

PMID- 27022668
TI  - Aqueous two-phase system purification for superoxide dismutase induced by
      menadione from Phanerochaete chrysosporium.
AB  - In the present work, the partitioning behavior of menadione-induced superoxide
      dismutase (SOD; EC 1.15.1.1), an antioxidant enzyme that has various applications
      in the medical and cosmetic industries, from the white rot fungus Phanerochaete
      chrysosporium has been characterized on different types of aqueous two-phase
      systems (ATPSs) (poly(ethylene glycol)/polypropylene glycol (PEG/PPG)-dextran,
      PEG-salt and PPG-salt). PEG-salt combinations were found most optimal systems for
      the purification of SOD. The best partition conditions were found using the PEG
      3350 24% and K2HPO4 5% (w/w) with pH 7.0 at 25  degrees C. The partition
      coefficient of total SOD activity and total protein concentration observed in
      this system were 0.17 and 6.65, respectively, with the recovery percentage as
      78.90% in the bottom phase and 13.17% in the top phase. The highest purification
      fold for SOD from P. chrysosporium was found as 6.04 in the bottom phase of PEG
      3350%24 - K2HPO4%5 (w/w) system with pH 7.0. SOD purified from P. chrysosporium
      was determined to be a homodimer in its native state with a molecular weight of
      60  +/- 4 kDa. Consequently, simple and only one step PEG-salt ATPS system was
      developed for SOD purification from P. chrysosporium.

PMID- 27022669
TI  - Modelling and characterisation of a ultrasound-actuated needle for improved
      visibility in ultrasound-guided regional anaesthesia and tissue biopsy.
AB  - Clear needle visualisation is recognised as an unmet need for ultrasound guided
      percutaneous needle procedures including regional anaesthesia and tissue biopsy.
      With inadequate needle visibility, these procedures may result in serious
      complications or a failed operation. This paper reports analysis of the modal
      behaviour of a previously proposed ultrasound-actuated needle configuration,
      which may overcome this problem by improving needle visibility in colour Doppler
      imaging. It uses a piezoelectric transducer to actuate longitudinal resonant
      modes in needles (outer diameter 0.8-1.2mm, length>65mm). The factors that affect
      the needle's vibration mode are identified, including the needle length, the
      transducer's resonance frequency and the gripping position. Their effects are
      investigated using finite element modelling, with the conclusions validated
      experimentally. The actuated needle was inserted into porcine tissue up to 30mm
      depth and its visibility was observed under colour Doppler imaging. The
      piezoelectric transducer is able to generate longitudinal vibration with peak-to
      peak amplitude up to 4MUm at the needle tip with an actuating voltage of 20Vpp.
      Actuated in longitudinal vibration modes (distal mode at 27.6kHz and transducer
      mode at 42.2kHz) with a drive amplitude of 12-14Vpp, a 120mm needle is delineated
      as a coloured line in colour Doppler images, with both needle tip and shaft
      visualised. The improved needle visibility is maintained while the needle is
      advanced into the tissue, thus allowing tracking of the needle position in real
      time. Moreover, the needle tip is highlighted by strong coloured artefacts around
      the actuated needle generated by its flexural vibration. A limitation of the
      technique is that the transducer mode requires needles of specific lengths so
      that the needle's resonance frequency matches the transducer. This may restrict
      the choice of needle lengths in clinical applications.

PMID- 27022670
TI  - Semantic and phonological influences on visual word learning in a transparent
      language.
AB  - Orthographic representations of words are indispensable for reading fluency. The
      ways in which these representations are developed and their resistance to decay
      are hotly debated topics. The aim of this study was to investigate the influence
      of semantic and phonological representations on the formation of orthographic
      representations in a transparent orthography. In order to achieve this objective,
      an experiment with three conditions was carried out. In the first condition, a
      group of university students were asked to repeatedly read 10 new words after
      semantic and phonological training, in the second condition another group of
      participants read the new words after phonological training, and in the third
      condition participants read without previous training. Finally, a follow-up
      session was performed to test the resistance to decay of the orthographic
      representations. The results showed that participants who had received semantic
      training formed the representations faster than participants in the other
      conditions, as indicated by the decrease in length effect. These results indicate
      the important role of previous knowledge when people face new written words. A
      month later these orthographic representations still remained in the lexicon of
      the participants.

PMID- 27022671
TI  - How Much do Needlestick Injuries Cost? A Systematic Review of the Economic
      Evaluations of Needlestick and Sharps Injuries Among Healthcare Personnel.
AB  - OBJECTIVE To provide an overview of the economic aspects of needlestick and
      sharps injury (NSI) management among healthcare personnel (HCP) within a Health
      Technology Assessment project to evaluate the impact of safety-engineered devices
      on health care METHODS A systematic review of economic analyses related to NSIs
      was performed in accordance with the PRISMA statement and by searching PubMed and
      Scopus databases (January 1997-February 2015). Mean costs were stratified by
      study approach (modeling or data driven) and type of cost (direct or indirect).
      Costs were evaluated using the CDC operative definition and converted to 2015
      International US dollars (Int$). RESULTS A total of 14 studies were retrieved: 8
      data-driven studies and 6 modeling studies. Among them, 11 studies provided
      direct and indirect costs and 3 studies provided only direct costs. The median of
      the means for aggregate (direct + indirect) costs was Int$747 (range, Int$199
      Int$1,691). The medians of the means for disaggregated costs were Int$425 (range,
      Int$48-Int$1,516) for direct costs (9 studies) and Int$322 (range, Int$152
      Int$413) for indirect costs (6 studies). When compared with data-driven studies,
      modeling studies had higher disaggregated and aggregated costs, but data-driven
      studies showed greater variability. Indirect costs were consistent between
      studies, mostly referring to lost productivity, while direct costs varied widely
      within and between studies according to source infectivity, HCP susceptibility,
      and post-exposure diagnostic and prophylactic protocols. Costs of treating
      infections were not included, and intangible costs could equal those associated
      with NSI medical evaluations. CONCLUSIONS NSIs generate significant direct,
      indirect, potential, and intangible costs, possibly increasing over time.
      Economic efforts directed at preventing occupational exposures and infections,
      including provision of safety-engineered devices, may be offset by the savings
      from a lower incidence of NSIs. Infect Control Hosp Epidemiol 2016;37:635-646.

PMID- 27022672
TI  - Improvement in Pain After Lumbar Spine Surgery: The Role of Preoperative
      Expectations of Pain Relief.
AB  - OBJECTIVES: Improvement in pain is a major expectation of patients undergoing
      lumbar spine surgery. MATERIALS AND METHODS: Among 422 patients, the goal of this
      prospective study was to measure 2-year postoperative pain and to determine
      whether this outcome varied according to patient and clinical characteristics,
      including amount of pain relief expected preoperatively. Before surgery patients
      completed valid questionnaires that addressed clinical characteristics and
      expectations for pain improvement. Two years after surgery patients reported how
      much pain improvement they actually received. RESULTS: The mean age was 56 years
      old and 55% were men. Two years after surgery 11% of patients reported no
      improvement in pain, 28% reported a little to moderate improvement, 44% reported
      a lot of improvement, and 17% reported complete improvement. In multivariable
      analysis, patients reported less pain improvement if, before surgery, they
      expected greater pain improvement (odds ratio [OR] 1.4), had a positive screen
      for depression (OR 1.7), were having revision surgery (OR 1.6), had surgery at L4
      or L5 (OR 2.5), had a degenerative diagnosis (OR 1.6), and if, after surgery,
      they had another surgery (OR 2.8) and greater back (OR 1.3) and leg (OR 1.1) pain
      (all variables P<=0.05). CONCLUSIONS: Pain is not uncommon after lumbar surgery
      and is associated with a network of clinical, surgical, and psychological
      variables. This study provides evidence that patients' expectations about pain
      are an independent variable in this network. Because expectations are potentially
      modifiable this study supports addressing pain-related expectations with patients
      before surgery through discussions with surgeons and through formal preoperative
      patient education.

PMID- 27022673
TI  - Development and Preliminary Testing of a Screening Measure of Acceptance and
      Willingness in Relation to Pain, Fatigue, and Sadness in Chronic Pain.
AB  - BACKGROUND: The manner in which one responds to the experience of chronic pain is
      a primary determinant of pain-related distress and disruptions in functioning. In
      particular, responses to pain that reflect substantial unwillingness, or a lack
      of acceptance, in relation to pain are reliably associated with greater
      difficulties in comparison with responses that reflect willingness and
      acceptance. To date, several multi-item self-report assessments have been
      developed to evaluate pain-related willingness and acceptance. The purpose of the
      present research was to develop and evaluate a single item measure, the
      Acceptance and Willingness screener (AWS). METHODS: Participants included 172
      individuals with chronic pain. The AWS consisted of 4 statements, reflecting
      various degrees of acceptance and willingness to experience pain, and
      participants were asked to endorse the statement that was most reflective of
      their views. RESULTS: Overall, responses were fairly evenly distributed across
      the statements (range, 20% to 29%). Correlation and regression results indicated
      significant associations between AWS responses and measures of pain intensity,
      depression, pain interference, and engagement in activity. Furthermore, when
      individuals were grouped according to the statement endorsed, significant between
      group differences were indicated across these same measures. Differences were
      particularly pronounced for groups endorsing the lowest levels of acceptance and
      willingness and those endorsing the highest. CONCLUSIONS: These results
      correspond with previous work and provide initial support for the validity of a
      single item screening measure of acceptance and willingness in chronic pain.

PMID- 27022675
TI  - Are Passive Physical Modalities Effective for the Management of Common Soft
      Tissue Injuries of the Elbow?: A Systematic Review by the Ontario Protocol for
      Traffic Injury Management (OPTIMa) Collaboration.
AB  - OBJECTIVE: To evaluate the effectiveness of passive physical modalities for the
      management of soft tissue injuries of the elbow. METHODS: We systematically
      searched MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central Register of
      Controlled Trials from 1990 to 2015. Studies meeting our selection criteria were
      eligible for critical appraisal. Random pairs of independent reviewers critically
      appraised eligible studies using the Scottish Intercollegiate Guidelines Network
      criteria. We included studies with a low risk of bias in our best evidence
      synthesis. RESULTS: We screened 6618 articles; 21 were eligible for critical
      appraisal and 9 (reporting on 8 randomized controlled trials) had a low risk of
      bias. All randomized controlled trials with a low risk of bias focused on lateral
      epicondylitis. We found that adding transcutaneous electrical nerve stimulation
      to primary care does not improve the outcome of patients with lateral
      epicondylitis. We found inconclusive evidence for the effectiveness of: (1) an
      elbow brace for managing lateral epicondylitis of variable duration; and (2)
      shockwave therapy or low-level laser therapy for persistent lateral
      epicondylitis. DISCUSSION: Our review suggests that transcutaneous electrical
      nerve stimulation provides no added benefit to patients with lateral
      epicondylitis. The effectiveness of an elbow brace, shockwave therapy, or low
      level laser therapy for the treatment of lateral epicondylitis is inconclusive.
      We found little evidence to inform the use of passive physical modalities for the
      management of elbow soft tissue injuries.

PMID- 27022674
TI  - Fibromyalgia and Chronic Pain Syndromes: A White Paper Detailing Current
      Challenges in the Field.
AB  - This manuscript, developed by a group of chronic pain researchers and clinicians
      from around the world, aims to address the state of knowledge about fibromyalgia
      (FM) and identify ongoing challenges in the field of FM and other chronic pain
      syndromes that may be characterized by pain
      centralization/amplification/hypersensitivity. There have been many exciting
      developments in research studies of the pathophysiology and treatment of FM and
      related syndromes that have the potential to improve the recognition and
      management of patients with FM and other conditions with FM-like pain. However,
      much of the new information has not reached all clinicians, especially primary
      care clinicians, who have the greatest potential to use this new knowledge to
      positively impact their patients' lives. Furthermore, there are persistent
      misconceptions about FM and a lack of consensus regarding the diagnosis and
      treatment of FM. This paper presents a framework for future global efforts to
      improve the understanding and treatment of FM and other associated chronic pain
      syndromes, disseminate research findings, identify ways to enhance advocacy for
      these patients, and improve global efforts to collaborate and reach consensus
      about key issues related to FM and chronic pain in general.

PMID- 27022676
TI  - The Effects of Bisphenol A Exposure at Different Developmental Time Points in an
      Androgen-Sensitive Neuromuscular System in Male Rats.
AB  - The industrial plasticizer bisphenol A (BPA) is a ubiquitous endocrine disruptor
      to which the general human population is routinely exposed. Although BPA is well
      known as an estrogenic mimic, there have been some suggestions that this compound
      may also alter activity at the androgen receptor. To determine whether BPA does
      have antiandrogenic properties, we evaluated BPA effects in the spinal nucleus of
      the bulbocavernosus and dorsolateral nucleus, sexually dimorphic groups of motor
      neurons in the lumbar spinal cord that are critically dependent on androgens for
      survival and maintenance, as well as the monomorphic retrodorsolateral nucleus.
      In experiment 1, we administered varying concentrations of BPA to juvenile rats
      pre- and postnatally and examined both the number and size of motor neurons in
      adulthood. In experiment 2, different doses of BPA were given to adult rats for
      28 days, after which the soma size of motor neurons were measured. Although no
      effect of BPA on neural survival or soma size was noted after perinatal BPA
      exposure, BPA exposure did result in a decrease in soma size in all motor neuron
      pools after chronic exposure in adulthood. These findings are discussed with
      regard to putative antiandrogenic effects of BPA; we argue that BPA is not
      antiandrogenic but is acting through nonandrogen receptor-dependent mechanisms.

PMID- 27022677
TI  - Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy
      in Mice.
AB  - Environmental and occupational exposure to bisphenol A (BPA), a chemical widely
      used in polycarbonate plastics and epoxy resins, has received much attention in
      female reproductive health due to its widespread toxic effects. Although BPA has
      been linked to infertility and recurrent miscarriage in women, the impact of its
      exposure on uterine function during early pregnancy remains unclear. In this
      study, we addressed the effect of prolonged exposure to an environmental relevant
      dose of BPA on embryo implantation and establishment of pregnancy. Our studies
      revealed that treatment of mice with BPA led to improper endometrial epithelial
      and stromal functions thus affecting embryo implantation and establishment of
      pregnancy. Upon further analyses, we found that the expression of progesterone
      receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest
      derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues.
      Previous studies have shown that HAND2 controls embryo implantation by repressing
      fibroblast growth factor and the MAPK signaling pathways and inhibiting
      epithelial proliferation. Interestingly, we observed that down-regulation of PGR
      and HAND2 expression in uterine stroma upon BPA exposure was associated with
      enhanced activation of fibroblast growth factor and MAPK signaling in the
      epithelium, thus contributing to aberrant proliferation and lack of uterine
      receptivity. Further, the differentiation of endometrial stromal cells to
      decidual cells, an event critical for the establishment and maintenance of
      pregnancy, was severely compromised in response to BPA. In summary, our studies
      revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely
      affects implantation and the establishment of pregnancy.

PMID- 27022679
TI  - Efficacy of High-Dose Supplementation With Oral Vitamin D3 on Depressive Symptoms
      in Dialysis Patients With Vitamin D3 Insufficiency: A Prospective, Randomized,
      Double-Blind Study.
AB  - Psychological problems are common among end-stage renal disease patients
      undergoing dialysis. We aim to evaluate whether high-dose vitamin D3 (VD3)
      supplementation has beneficial effects on depressive symptoms in dialysis
      patients. This prospective, randomized, and double-blind trial includes 746
      dialysis patients with depression treated in 3 hospitals in Southeast China.
      Depression was diagnosed according to the Diagnostic and Statistical Manual of
      Mental Disorders criteria. Patients were randomly assigned to 52-week treatment
      of oral 50,000 IU/wk VD3 (cholecalciferol) (test group) or a placebo (control
      group). The presence of depressive symptoms was evaluated using the Chinese
      version of Beck Depression Inventory (BDI) II both before and after treatment.
      Sociodemographic data, clinical data, nutritional indexes, inflammatory
      biomarkers, and plasma VD3 concentrations were also determined. Finally, 726
      patients completed the experiments, including 362 tested patients and 364
      controls. After 52 weeks, the depressive symptoms were not significantly improved
      in the test group (mean BDI II scores changed from -1.1 +/- 0.3 to -3.1 +/- 0.6)
      versus the control group. Multivariable logistic regression showed BDI scores
      were not significantly improved in the test group versus the control group with
      adjustment for age, sex, comorbidity index, dialysis modality, or (OH)D levels
      (multivariable-adjusted mean change or MAMC [95% confidence interval (CI)], -2.3
      [-2.48 to -1.83]) in the whole dialysis population. After stratification by
      depression types, the findings do support a significant relationship between the
      VD3 supplementation and the improvement in BDI II scores in dialysis patients
      with vascular depression (MAMC [95% CI], -4.4 [-5.08 to -2.76]), but the effect
      was not significant for major depressive disorders (MAMC [95% CI], -0.9 [-1.52 to
      -0.63]). The high-dose VD3 supplementation did not significantly reduce the
      depressive symptoms in our total dialysis population, but a beneficial effect on
      vascular depression was found, probably mainly based on the improvement of
      cardiovascular risk factors. 

PMID- 27022678
TI  - De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH
      Mediated Ovarian Follicular Cell Differentiation and Female Fertility.
AB  - Retinoic acid (RA) is the active form of vitamin A and is synthesized from
      retinol by two key enzymes, alcohol dehydrogenase (ADH) and acetaldehyde
      dehydrogenase (ALDH). As the physiological precursor of RA, retinol impacts
      female reproductive functions and fertility. The expression of Adh1 and Adh5 as
      well as Aldh1a1 and Aldh1a7 are significantly increased in the ovaries of mice
      treated with equine chorionic gonadotropin/FSH. The RA receptor is expressed and
      localized in granulosa cells and is activated by endogenous RA as indicated by
      LacZ expression in granulosa cells of RA-responsive transgene-LacZ transgenic
      mice (RA reporter mice). Coinjection of the ADH inhibitor, 4-methylpyrazole, with
      equine chorionic gonadotropin significantly decreases the number and
      developmental competence of oocytes ovulated in response to human chorionic
      gonadotropin/LH as compared with controls. Injections of RA completely reverse
      the effects of the inhibitor of ovulation and oocyte development. When mice were
      fed a retinol-free, vitamin A-deficient diet that significantly reduced the serum
      levels of retinol, the expression of the LH receptor (Lhcgr) was significantly
      lower in the ovaries of the vitamin A-deficient mice, and injections of human
      chorionic gonadotropin failed to induce genes controlling ovulation. These
      results indicate that ovarian de novo biosynthesis of RA is required for the
      follicular expression of Lhcgr in granulosa cells and their ability to respond to
      the ovulatory LH surge.

PMID- 27022680
TI  - PI3K regulates BMAL1/CLOCK-mediated circadian transcription from the Dbp
      promoter.
AB  - The circadian rhythm generated by circadian clock underlies a molecular mechanism
      of rhythmic transcriptional regulation by transcription factor BMAL1/CLOCK.
      Importantly, the circadian clock is coordinated by exogenous cues to accommodate
      to changes in the external environment. However, the molecular mechanisms by
      which intracellular-signaling pathways mediate the adjustments of the circadian
      transcriptional rhythms remain unclear. In this study, we found that
      pharmacological inhibition or shRNA-mediated knockdown of phosphatidylinositol 3
      kinase (PI3K) blocked upregulation of Dbp mRNA induced by serum shock in NIH 3T3
      cells. Moreover, the inhibition of PI3K significantly reduced the promoter
      activity of the Dbp gene, as well as decreased the recruitment of BMAL1/CLOCK to
      the E-box in the Dbp promoter. Interestingly, the inhibition of PI3K blocked
      heterodimerization of BMAL1 and CLOCK. Our findings suggest that PI3K signaling
      plays a modulatory role in the regulation of the transcriptional rhythm of the
      Dbp gene by targeting BMAL1 and CLOCK. 

PMID- 27022681
TI  - Fabrication and Operation of Acoustofluidic Devices Supporting Bulk Acoustic
      Standing Waves for Sheathless Focusing of Particles.
AB  - Acoustophoresis refers to the displacement of suspended objects in response to
      directional forces from sound energy. Given that the suspended objects must be
      smaller than the incident wavelength of sound and the width of the fluidic
      channels are typically tens to hundreds of micrometers across, acoustofluidic
      devices typically use ultrasonic waves generated from a piezoelectric transducer
      pulsating at high frequencies (in the megahertz range). At characteristic
      frequencies that depend on the geometry of the device, it is possible to induce
      the formation of standing waves that can focus particles along desired fluidic
      streamlines within a bulk flow. Here, we describe a method for the fabrication of
      acoustophoretic devices from common materials and clean room equipment. We show
      representative results for the focusing of particles with positive or negative
      acoustic contrast factors, which move towards the pressure nodes or antinodes of
      the standing waves, respectively. These devices offer enormous practical utility
      for precisely positioning large numbers of microscopic entities (e.g., cells) in
      stationary or flowing fluids for applications ranging from cytometry to assembly.

PMID- 27022682
TI  - A Nursing Semester in a Developing Country: Lessons Learned.
AB  - Nurses need to gain knowledge and experience that will assist them to practice in
      a global environment. This article shares the unique experiences of a university
      in providing a semester of nursing study in a developing country. What makes this
      experience unique is that theory and clinical courses were taught similarly on
      both the US and Ugandan campuses. Benefits and challenges of the semester are
      discussed, as well as details of planning, implementation, and posttrip
      conclusions. 

PMID- 27022683
TI  - An Integrative Review of Cybercivility in Health Professions Education.
AB  - Although incivility in higher education has been widely described, little
      evidence exists regarding incivility among health professions students in online
      environments. This study aims to integrate literature on cybercivility in health
      professions education. The extent to which health professions students and
      faculty experience cyberincivility, the direct and indirect effects and actions
      taken after cyberincivility, and themes that guide facilitation of cybercivility
      are discussed. Efforts to prevent cyberincivility can be achieved through focused
      education on cybercivility, development of clear policies related to its
      consequences, and formulation of guidelines for both student and faculty behavior
      online. 

PMID- 27022684
TI  - Transition Program to Promote Incoming Nursing Student Success in Higher
      Education.
AB  - A new model for addressing first-generation and minority student issues when
      starting nursing school was implemented using an interactive, peer-developed, 2
      day program to create a sense of community and relieve anxiety. The program
      focused on students' needs, engagement, networking, first-hand experience with
      resources and methods to reduce cultural dissonance. Participation included
      critiquing modeling of proper clinical attire, meeting with peer mentors, and
      locating important campus resources. The program, conducted by minority students
      under the supervision and guidance of faculty mentors, received excellent
      evaluations.

PMID- 27022685
TI  - Activation of dormant follicles: a new treatment for premature ovarian failure?
AB  - PURPOSE OF REVIEW: Premature ovarian failure (POF) is diagnosed by amenorrhea
      before 40 years of age. Owing to exhaustion of follicles in POF ovaries, egg
      donation is the only option. Although menstrual cycles cease in POF patients,
      some of them still contain residual dormant follicles in ovaries. Recently, we
      developed a new infertility treatment and named it as in-vitro activation (IVA),
      which enables POF patients to conceive using their own eggs by activation of
      residual dormant follicles. Here, we summarize data showing the potential of IVA
      as a new infertility treatment for POF patients. RECENT FINDINGS: Transgenic
      mouse studies revealed that the stimulation of phosphatidylinositol-3-kinase-AKT
      forkhead box O3 pathway activated dormant primordial follicles. In murine and
      human ovaries, the phosphatase and tensin homolog inhibitors and
      phosphatidylinositol-3-kinase activators were demonstrated to activate dormant
      primordial follicles in in-vitro cultures. Subsequent studies showed that ovarian
      fragmentation suppressed Hippo signaling pathway, leading to ovarian follicle
      growth. Combining these two methods in an IVA approach followed by ovarian tissue
      autotransplantation, successful follicle growth, and pregnancies were reported in
      POF patients. Currently, two healthy babies were delivered, together with two
      additional pregnancies. SUMMARY: IVA treatment is a potential infertility therapy
      for POF patients who have residual follicles.

PMID- 27022686
TI  - Superconductivity and itinerant ferromagnetism of Y9Co7 probed by ac
      susceptibility.
AB  - The ac magnetic susceptibility of a single crystal sample of the compound Y9Co7
      has been measured in applied dc fields ranging from 0-6.7 kOe by utilizing a
      tunnel diode resonator circuit. In agreement with previous measurements on this
      material, a superconducting transition has been observed to occur at T(SC)~2.5 K.
      A broad maximum has been observed in the zero field susceptibility measurements
      from 2.5 K  <  T  <  8 K and its behavior with applied dc magnetic fields is
      consistent with that of the itinerant ferromagnet ZrZn2, which supports previous
      claims of itinerant ferromagnetism in this compound. The susceptibility has also
      been measured as a function of applied magnetic field and the results indicate
      that the actual Curie temperature for this system is higher than that suggested
      by previous reports based on Arrott plots constructed from dc magnetization.

PMID- 27022687
TI  - Primary Endodermal Epithelial Cell Culture from the Yolk Sac Membrane of Japanese
      Quail Embryos.
AB  - We established an endodermal epithelial cell culture model (EEC) for studying the
      function of certain enzymes and proteins in mediating nutrient utilization by
      avian embryos during development. Fertilized Japanese quail eggs were incubated
      at 37  degrees C for 5 days and then yolk sac membranes (YSM) were collected to
      establish the EEC culture system. We isolated the embryonic endoderm layer from
      YSM, and sliced the membrane into 2 - 3 mm pieces and partially digested with
      collagenase before seeding in 24-well culture plates. The EECs proliferate out of
      the tissue and are ready for cell culture studies. We found that the EECs had
      typical characteristics of YSM in vivo, for example, accumulation of lipid
      droplets, expression of sterol O-acyltransferase and lipoprotein lipase. The
      partial digestion treatment significantly increased the successful rate of EEC
      culture. Utilizing the EECs, we demonstrated that the expression of SOAT1 was
      regulated by the cAMP dependent protein kinase A related pathway. This primary
      Japanese quail EEC culture system is a useful tool to study embryonic lipid
      transportation and to clarify the role of genes involved in mediating nutrient
      utilization in YSM during avian embryonic development. 

PMID- 27022688
TI  - Breast cancer risk feedback to women in the UK NHS breast screening population.
AB  - INTRODUCTION: There are widespread moves to develop risk-stratified approaches to
      population-based breast screening. The public needs to favour receiving breast
      cancer risk information, which ideally should produce no detrimental effects.
      This study investigates risk perception, the proportion wishing to know their 10
      year risk and whether subsequent screening attendance is affected. METHODS: Fifty
      thousand women attending the NHS Breast Screening Programme completed a risk
      assessment questionnaire. Ten-year breast cancer risks were estimated using a
      validated algorithm (Tyrer-Cuzick) adjusted for visually assessed mammographic
      density. Women at high risk (?8%) and low risk (<1%) were invited for face-to
      face or telephone risk feedback and counselling. RESULTS: Of those invited to
      receive risk feedback, more high-risk women, 500 out of 673 (74.3%), opted to
      receive a consultation than low-risk women, 106 out of 193 (54.9%) (P<0.001).
      Women at high risk were significantly more likely to perceive their risk as high
      (P<0.001) and to attend their subsequent mammogram (94.4%) compared with low-risk
      women (84.2%; P=0.04) and all attendees (84.3%; ?0.0001). CONCLUSIONS: Population
      based assessment of breast cancer risk is feasible. The majority of women wished
      to receive risk information. Perception of general population breast cancer risk
      is poor. There were no apparent adverse effects on screening attendance for high
      risk women whose subsequent screening attendance was increased.

PMID- 27022689
TI  - Germinated Waxy Black Rice Suppresses Weight Gain in High-Fat Diet-Induced Obese
      Mice.
AB  - This study was performed to investigate the antiobesity effect of germinated waxy
      black rice (GWBR) in high-fat diet (HFD)-induced obese mice. The mice were
      divided into a normal diet (ND) group, HFD group, and 2 test groups for 8 weeks:
      2.5% GWBR-supplemented (GWBR-2.5) group and 5% GWBR-supplemented (GWBR-5) group.
      Supplementing with GWBR significantly reduced body weight gain and lipid
      accumulation in the liver and adipose tissue compared to the HFD control group.
      Triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol
      levels in serum were decreased by GWBR supplementation, whereas high-density
      lipoprotein-cholesterol level significantly increased. In addition, mRNA levels
      of transcriptional factors, such as peroxisome proliferator-activated receptor
      gamma, CCAAT enhancer-binding protein (C/EBP)-alpha, C/EBP-beta, sterol
      regulatory element-binding protein-1c, and related genes, including adipocyte
      fatty acid-binding protein, fatty acid synthase, and lipoprotein lipase, were
      significantly lower in the GWBR groups. However, lipolytic enzymes, such as
      hormone-sensitive lipase, adipose TG lipase, and carnitine palmitoyltransferase
      1, and uncoupling protein 2 mRNA levels were significantly higher in GWBR
      supplemented mice. These results suggest that GWBR exerts antiobesity effects by
      decreasing lipid accumulation and promoting lipolysis in HFD-induced obese mice. 

PMID- 27022690
TI  - Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco
      Transient Expression System.
AB  - Visualization of dynamic signaling events in live cells has been a challenge. We
      expanded an established transient expression system, the biomolecular fluorescent
      complementation (BiFC) assay in tobacco epidermal cells, from testing protein
      protein interaction to monitoring spatial distribution of signal transduction in
      plant cells. In this protocol, we used the BiFC assay to show that the
      interaction and the signaling between the Arabidopsis MAPKKK YODA and MAPK6 occur
      at the plasma membrane. When the scaffold protein BASL was co-expressed, the YODA
      MAPK interaction redistributed and spatially co-polarized with CFP-BASL. This
      modified tobacco expression system allows for quick examination of signaling
      localization and dynamic changes (less than 4 days) and can accommodate multiple
      of fluorescent protein colors (at least three). We also presented detailed
      methods to quantify protein distribution (asymmetric spatial localization, or
      "polarization") in tobacco cells. This advanced tobacco expression system has a
      potential to be used widely for quick testing of dynamic signaling events in live
      plant cells. 

PMID- 27022691
TI  - Uncommon Pyrazoyl-Carboxyl Bifunctional Ligand-Based Microporous Lanthanide
      Systems: Sorption and Luminescent Sensing Properties.
AB  - Seven new isostructural lanthanide metal-organic frameworks (Ln-MOFs),
      [Ln(Hpzbc)2(NO3)].H2O (1-Ln, Ln = Nd(3+), Sm(3+), Eu(3+), Gd(3+), Tb(3+), Er(3+),
      and Yb(3+) ions, H2pzbc = 3-(1H-pyrazol-3-yl) benzoic acid), with one-dimensional
      (1D) channels decorated by nitrate anions and pyrazoyl groups have been
      constructed. 1-Ln, as revealed by structural analysis, represent uncommon
      microporous 3D Ln-pyrazoyl-carboxyl systems using pyrazoyl-carboxyl bifunctional
      ligands as bridges. The luminescent investigations show that 1-Eu is an excellent
      MOF-based fluorescent probe, with high sensitivity, selectivity, and simple
      regeneration, for environmentally relevant Fe(3+) and Cr2O7(2-) ions. 1-Eu also
      presents highly selective capture for CO2 over N2 and CH4 due to the multiple
      binding sites for CO2 molecules, which were supported by Grand Canonical Monte
      Carlo (GCMC) simulations. 

PMID- 27022692
TI  - [Not Available].

PMID- 27022693
TI  - [Anesthesiological aspects in non-cardiac surgery for patients with congenital
      heart disease].
AB  - There are about 6000 children with congenital heart diseases (CHD) born in
      Germany each year. This number is constant irrespective of the improving prenatal
      diagnostics. As many of the surgically treated patients now reach adulthood, due
      to the development of treatments and operations for CHD, there is an increasing
      likelihood that surgically treated patients with CHD come to be treated in non
      specialized hospitals at any time. Furthermore, it enables anesthesiologists, who
      have not so much opportunities to treat patients with CHD, to handle such
      patients safely and successfully, when further knowledge of underlying heart
      failure and related pathophysiologic characteristics are known. The purpose of
      this article is to achieve a respectful and confident treatment for patients who
      had corrective or palliative operations for CHD. 

PMID- 27022694
TI  - [Not Available].
AB  - Tuberculosis is a rare disease in Germany. This is the result of systematic
      treatment, contact tracing, and supervision of public health institutions, but
      even more of good nutrition and immunity of the population. Considering migration
      waves, a higher incidence of non-diagnosed tuberculosis may be expected. Due to
      the airborne type of infection and constant manipulation of the airway, those
      working in anesthesia, intensive care and emergency medicine are exposed to an
      increased risk of infection with tuberculosis. To avoid hospital and community
      infection, several guidelines of national and international organizations are
      available.This article gives a summary of the mechanism and probability of
      infection, diagnosis of infection andpathogen detection; important guidelines are
      referred to, and everyday situations with risk of infection and their avoidance
      are described. The message is that self-protection should be possible by
      information and awareness. 

PMID- 27022695
TI  - [Not Available].
AB  - Skin and soft tissue infections may progress rapidly and take a fatal ending
      unless not treated in time. A 44-year old male patient without any pre-existing
      conditions got hospitalized with a bursitis ofthe right olecranon and unspecific
      general symptoms. Within a short period of time he became critically ill due this
      seemingly harmless infection. We describe our approach leading to the right
      diagnoses and the treatment of this unexpected progress. 

PMID- 27022696
TI  - [Not Available].

PMID- 27022697
TI  - [Resuscitation - Basic Life Support in adults and application of automatic
      external defibrillators].
AB  - Witnesses of a sudden cardiac arrest play a key-role in resuscitation. Lay
      persons should therefore be trained to recognize that a collapsed person who is
      not breathing at all or breathing normally might suffer from cardiac arrest.
      Information of professional emergency medical staff by lay-persons and their
      initiation of cardio-pulmonary-resuscitation-measures are of great importance for
      cardiac-arrest victims. Ambulance-dispatchers have to support lay-rescuers via
      telephone. This support includes the localisation of the nearest Automatic
      External Defibrillator (AED). Presentation of agonal breathing or convulsions due
      to brain-hypoxia need to be recognized as potential early signs of cardiac
      arrest. In any case of cardiac arrest chest-compressions need to be started.
      There is insufficiant data to recommend "chest-compression-only"-CPR as being
      equally sufficient as cardio-pulmonary-resuscitation including ventilation.
      Rescuers trained in ventilation should therefore combine compressions and
      ventilations at a 30:2-ratio. Movement of the chest is being used as a sign of
      sufficient ventilation. High-quality chest-compressions of at least 5 cm of
      depth, not exceeding 6 cm, are recommended at a ratio of 100-120 chest
      conpressions/min. Interruption of chest-compression should be avoided. At busy
      public places AED should be available to enable lay-rescuers to apply early
      defibrillation. 

PMID- 27022698
TI  - [Resuscitation - Adult advanced life support].
AB  - Enhanced measures for resuscitation of adults are based on basic measures of
      resuscitation. The central elements are highly effective chest compressions and
      avoidance of disruptions that are associated with poor patient outcomes that
      occur within seconds. The universal algorithm distinguishes the therapy for
      ventricular fibrillation from the therapy in asystole or pulseless electrical
      activity (PEA) by the need of defibrillation, and amiodarone administration in
      the former. Defibrillation is biphasic. In all other aspects, there are no
      differences in therapy. In each episode of cardiac arrest, reversible causes
      should be excluded or treated. For the diagnosis during resuscitation, sonography
      can be helpful. What is new in the 2015 ERC recommendations is the use of
      capnography, which can be used for the assessment of ROSC (return of spontaneous
      circulation), ventilation, resuscitation and intubation quality. Mechanical
      resuscitation devices can be used in selected situations. Successful primary
      resuscitation should be directly followed by measures of the post-resuscitation
      care. 

PMID- 27022699
TI  - [Resuscitation - cardiopulmonary resuscitation in infants and children
      (paediatric life support)].
AB  - In children, severe emergencies and cardiorespiratory arrests in particular are
      relatively rare but time-critical events. As compared to adults, hypoxic arrests
      caused by respiratory disorders that may subsequently result in pulseless
      electrical activity or asystole are more prevalent. The current Paediatric Life
      Support (PLS) Guidelines 2015 of the European Resuscitation Council (ERC)
      acknowledge both limited scientific evidence and aspects of practicability. They
      also take into account the rather limitedpaediatric routine that most providers
      have as well as national and local infrastructural differences. Particular
      emphasis was put on early recognition and treatment of a critically ill or
      injured child, hence the prevention of cardiorespiratory arrest and the early
      start of lay rescuer interventions. There have been no major changes in the 2010
      algorithms, including retention of the ABC sequence (airway, breathing,
      circulation). 

PMID- 27022702
TI  - Design of Catalytic Peptides and Proteins Through Rational and Combinatorial
      Approaches.
AB  - This review focuses on recent progress in noncomputational methods to introduce
      catalytic function into proteins, peptides, and peptide assemblies. We discuss
      various approaches to creating catalytic activity and classification of
      noncomputational methods into rational and combinatorial classes. The section on
      rational design covers recent progress in the development of short peptides and
      oligomeric peptide assemblies for various natural and unnatural reactions. The
      section on combinatorial design describes recent advances in the discovery of
      catalytic peptides. We present the future prospects of these and other new
      approaches in a broader context, including implications for functional material
      design.

PMID- 27022703
TI  - NMC in 'much stronger position', review finds.
AB  - The Nursing and Midwifery Council has made substantial improvements after being
      given two years to get its house in order, an independent review has concluded.

PMID- 27022704
TI  - News digest September 16 2014.
AB  - A round-up of nursing and health stories from today's papers.

PMID- 27022705
TI  - Government criticised over sepsis care.
AB  - MPs have criticised the government for a 'lack of urgency' in preventing deaths
      from sepsis.

PMID- 27022707
TI  - News digest September 12 2014.
AB  - A round-up of nursing and health stories from today's papers.

PMID- 27022706
TI  - News digest September 15 2014.
AB  - A round-up of nursing and health stories from today's papers.

PMID- 27022708
TI  - Surrey council apologises for leaving pensioner alone for nine days without food,
      medication or water.
AB  - Surrey County Council has said it 'should have done more' for an 81-year-old
      woman who died after being left in her home without care for nine days.

PMID- 27022709
TI  - Queen's Nursing Institute to recognise the work of community nurses in supporting
      carers.
AB  - Community nurses and allied health professionals who support carers are to be
      recognised for their work during two 'champion days'.

PMID- 27022710
TI  - News digest September 11 2014.
AB  - A round-up of nursing and health stories from today's papers.

PMID- 27022711
TI  - Corrigendum: Isolation of exosomes by differential centrifugation: Theoretical
      analysis of a commonly used protocol.

PMID- 27022712
TI  - Erratum: Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for Biomedical
      Applications.
AB  - A correction was made to: Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for
      Biomedical Applications. There was an error with an author's given name. The
      author's name was corrected to: Katye M. Fichter from: Kathryn M. Fichter. 

PMID- 27022713
TI  - Development of a valid measurement instrument to understand self-regulatory
      driving practices among older drivers in Malaysia.
AB  - Self-regulatory driving is a term used to describe a strategy used by older
      drivers to preserve mobility and safety, through the adjustment of driving
      behaviors to match declining physical functions. It can be regarded as a way to
      prolong driving, or as a process leading to the cessation of driving. Previous
      studies have striven to explore and understand how older drivers self-regulate
      their driving. This paper aims to provide an overview of the relevant theories,
      to explicate the factors that contribute to the adoption of self-regulated
      driving and the scales used to measure self-regulatory behaviors. This paper also
      reports on the development and psychometric testing of a Self-Regulatory Driving
      Practices (SRDP) scale in the Malaysian context. Based on the reviewed theories,
      adoption of self-regulatory driving practices is a process and involves cognitive
      thinking that reflects a set of actions. Existing instruments to measure self
      regulatory driving practices have been developed and used to identify the
      behavioral components of self-regulation. Based on literature reviews and a
      thematic analysis from focus group discussions, a SRDP scale was developed,
      accommodating the Malaysian context. There were 498 surveys completed by older
      drivers for further psychometric testing purposes. Results revealed that the
      final 12-item SRDP scale (alpha=0.81) consists of four subscales that are
      planning, avoidance, reduction and alternatives. Suggestions for future research
      are also recommended. 

PMID- 27022715
TI  - Harnessing the power of microbial metabolism.
AB  - Microorganisms are rich repositories of genetic material encoding many activities
      of potential interest. Recent advances make identifying and exploiting the
      metabolic treasures of uncultured microbes an easier proposition. Improved
      expression vectors and metagenomic screening techniques make it easier to
      identify activities of interest. Synthetic biology and efficient genome editing
      techniques allow microbial genomes to be modified almost without restriction.
      Computational approaches based on organism-wide analysis of transcription,
      protein synthesis and metabolic fluxes make it possible to accurately predict the
      outcome of the metabolic processes and modifications required for optimization.
      Together these advances represent a major breakthrough in microbial biotechnology
      that is expected to yield new generations of tailor-made biocatalysts suitable
      for multiple biotechnological applications.

PMID- 27022716
TI  - Microwave-driven Synthesis of Iron Oxide Nanoparticles for Fast Detection of
      Atherosclerosis.
AB  - A fast and reproducible microwave-driven protocol has been developed for the
      synthesis of neridronate-functionalized nanoparticles. Starting from the
      synthesis of hydrophobic nanoparticles, our method is based on an adaptation from
      thermal decomposition method to microwave driven synthesis. The new methodology
      produces a decrease in the reaction times in comparison with traditional
      procedures. Moreover, the use of the microwave technology increases the
      reproducibility of the reactions, something important from the point of view of
      clinical applications. The novelty of this iron oxide nanoparticle is the
      attachment of Neridronate. The use of this molecule leads a bisphosphonate moiety
      towards the outside of the nanoparticle that provides Ca2+ binding properties in
      vitro and selective accumulation in vivo in the atheroma plaque. The protocol
      allows the synthesis and plaque detection in about 3 hr since the initial
      synthesis from organic precursors. Their accumulation in the atherosclerotic area
      in less than 1 hr provides a contrast agent particularly suitable for clinical
      applications.

PMID- 27022717
TI  - Design of tree structured matched wavelet for HRV signals of menstrual cycle.
AB  - An algorithm is presented for designing a new class of wavelets matched to the
      Heart Rate Variability (HRV) signals of the menstrual cycle. The proposed
      wavelets are used to find HRV variations between phases of menstrual cycle. The
      method finds the signal matching characteristics by minimising the shape feature
      error using Least Mean Square method. The proposed filter banks are used for the
      decomposition of the HRV signal. For reconstructing the original signal, the tree
      structure method is used. In this approach, decomposed sub-bands are selected
      based upon their energy in each sub-band. Thus, instead of using all sub-bands
      for reconstruction, sub-bands having high energy content are used for the
      reconstruction of signal. Thus, a lower number of sub-bands are required for
      reconstruction of the original signal which shows the effectiveness of newly
      created filter coefficients. Results show that proposed wavelets are able to
      differentiate HRV variations between phases of the menstrual cycle accurately
      than standard wavelets. 

PMID- 27022718
TI  - Simultaneous Determination of Baicalein and Baicalin in Human Plasma by High
      Performance Liquid Chromatograph-Tandem Spectrometry and its Application in a
      Food-Effect Pharmacokinetic Study.
AB  - BACKGROUND: Baicalein is a flavonoid isolated from skullcap and it is likely to
      exist in plasma at a low concentration because of the extensive first-pass
      metabolism in vivo. The aim of our study was to develop and fully validate a
      sensitive and selective HPLC-MS/MS method for simultaneous determination of
      baicalein and its main metabolite baicalin (baicalein-7-O-beta
      glucopyranuronoside) in human plasma. MATERIALS AND METHODS: Liquid-liquid
      extraction was used for pretreatment of plasma samples. The mobile phase
      consisted of aqueous phase A (0.5% formic acid in 3 mM ammonium acetate solution)
      and organic phase B (methanol-acetonitrile-formic acid, 50:50:0.5, v:v:v).
      Detection was performed on a triple-quadrupole tandem mass spectrometer using
      positive electrospray ionization. Quantification was performed by multiple
      reaction monitoring mode at m/z transitions of 271.1->123.1 for baicalein and
      447.1->271.0 for baicalin, respectively. RESULTS AND DISCUSSION: The calibration
      curve was linear over the range of 1~400 ng/mL (r(2)>0.99) for both baicalein and
      baicalin. The intra-day and inter-day precision values were below 6.84% for
      baicalein and 8.56% for baicalin at 3 quality control levels. The mean accuracy
      was 95.27 ~ 110.56%, 91.82 ~ 105.01% for baicalein and baicalin, respectively.
      Analytes were stable during sample storage and handling. CONCLUSIONS: The method
      was proved to be accurate and specific and was applied to a pharmacokinetic study
      of baicalein in healthy volunteers under both fasted and fed states.

PMID- 27022719
TI  - The Comparison of Biodistribution, Efficacy and Toxicity of Two PEGylated
      Liposomal Doxorubicin Formulations in Mice Bearing C-26 Colon Carcinoma: a
      Preclinical Study.
AB  - BACKGROUND: Over the past several years, the considerable attention has been
      progressively given to liposomal formulations of anthracyclines.
      SinaDoxosome((r)) (Exir Nano Sina Company, Iran) is a pegylated liposomal
      doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for
      treatment of some types of cancer. The aim of this study was to compare the
      biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome((r))
      with Caelyx((r)) in mice bearing C-26 colon carcinoma. METHODS AND RESULTS: Mice
      tumor size evaluation during the experimental period (28 days) showed comparable
      therapeutic efficacy of nano-formulations. The biodistribution studies showed no
      significant difference in DOX tissue concentration between Caelyx((r)) and
      SinaDoxosome((r)). DOX induced-ECG changes were not detected in nano
      formulations. No significant alteration was found in biochemical indexes of
      myocardial injury in mice exposed to nano-formulations in comparison with control
      mice. The tissue oxidative parameters such as lipid peroxidation, glutathione,
      catalase and superoxide dismutase was significantly changed as the results of
      free DOX treatment. However, the oxidative status of Caelyx((r)) and
      SinaDoxosome((r)) treated animals did not showed any changes. The experiment also
      revealed that apoptotic pathway was not activated in the heart of mice exposed to
      nano-formulations. CONCLUSIONS: Although this investigation showed that
      Caelyx((r)) and SinaDoxosome((r)) are similar in terms of biodistribution,
      efficacy and toxicity, appropriate clinical evaluations in patients should be
      considered.

PMID- 27022720
TI  - Crossmodal synesthetic congruency improves visual timing in dyslexic children.
AB  - Consistent with the temporal ventriloquism effect, synesthetic correspondence
      between the features of visual size and auditory pitch has been shown to modulate
      the performance of visual temporal order judgment (TOJ) in typical adults. Here
      in the two main experiments we recruited seventeen dyslexic children and twenty
      typically developing children to perform a visual TOJ task and measured their
      ability of synesthetic correspondence between visual size and auditory pitch. In
      Experiment 1, participants were shown two consecutively presented visual discs
      that were temporally flanked by two synesthetic congruent or incongruent auditory
      beeps. In Experiment 2, participants received a crossmodal matching test (visual
      size vs. auditory pitch). The results showed that compared to the typically
      developing group, dyslexic children benefited more from cross-modal synesthetic
      correspondence to partially compensate for their deficiency in visual TOJ task.
      The multisensory facilitation for timing performance was correlated with reading
      ability (Exp.1). Moreover, dyslexic children formed intact "congruent" matching
      of visually larger shapes to lower auditory pitch, and visually smaller shapes to
      higher auditory pitch, as did their typically developing peers (Exp 2). The
      results of our present study suggested general deficits of temporal processing in
      dyslexic children, However, with relatively intact ability of auditory pitch
      visual size matching, dyslexic children could separate visual events using
      auditory cues. The current study also indicates a feasible way to improve the
      reading ability by exploiting temporal ventriloquism effect, modulated by
      appropriate crossmodal synesthetic associations. 

PMID- 27022721
TI  - One-pot synthesis of a gold nanoparticle-Vmh2 hydrophobin nanobiocomplex for
      glucose monitoring.
AB  - HydrophobinVmh2 is a small amphiphilic protein, which self-assembles on different
      surfaces and naturally interacts with glucose. Here, we report on the synthesis
      of a nanobiocomplex made of polyethylene glycol, Vmh2 and gold nanoparticles by a
      one-step process and on its ability to recognise glucose in an aqueous solution
      at 0.3-0.6-1.2 mg ml(-1) concentrations. Even though the Vmh2 proteins are
      intrinsically bonded to the gold core, effective glucose interaction monitoring
      was demonstrated by using dynamic light scattering, ultraviolet-visible,
      polarization-modulated infrared reflection-absorption and x-ray photoelectron
      spectroscopies. Experimental results highlighted an affinity constant of 7.3 +/-
      0.3 mg ml(-1) between the nanobiosystem and the sugar, and a detection
      sensitivity of 0.13 +/- 0.06 a.u./mg ml(-1).

PMID- 27022722
TI  - Anaemia in Patients with Inflammatory Bowel Disease - A Nationwide Cross
      Sectional Study.
AB  - BACKGROUND: Anaemia is the most common complication in patients with inflammatory
      bowel disease (IBD). This study aims to assess the prevalence of anaemia in IBD
      patients and to know its characteristics with regard to the main IBD clinical
      features. METHODS: An observational cross-sectional multicentre study was
      conducted. We included all patients who had an appointment at the 15
      participating centres during the period of 1 month, and who met the following
      selection criteria: age >=18, diagnosis of IBD. Disease activity was evaluated by
      Harvey-Bradshaw Index (HBI) for Crohn's disease (CD), and by Simple Clinical
      Colitis Activity Index (SCCAI) for ulcerative colitis (UC). RESULTS: One thousand
      three hundred and thirteen patients, were included: 54.8% female, mean age 42.8
      (interquartile range (25th-75th): 31-53 years), 59% had a diagnosis of CD, 39% of
      UC and 2% IBD unclassified. The median follow-up since diagnosis was 7 years. The
      ongoing treatment was aminosalicylates (63.1%), corticosteroids (11.6%),
      immunomodulators (36.4%) and anti-tumour necrosis factor (27.3%). Anaemia was
      identified in 244 patients, representing a prevalence of 18.6% (95% CI 16.6
      20.9). A majority of cases (90%) have mild/moderate anaemia (mean haemoglobin
      11.3 +/- 0.8 g/dl). Anaemia was significantly higher in females (p = 0.006), but
      there were no differences between CDs (19.1%) and UCs (17.7%; p = 0.688). Anaemia
      was more frequent in patients with active disease (HBI >4; SCCAI >2) than in
      those in clinical remission (33.6 vs. 15.6%, p < 0.001) and in patients on
      steroids (36.8%) vs. other treatments (p < 0.001). Only 47% of patients with
      anaemia were under any specific treatment (oral iron 67%; intravenous iron 41%).
      CONCLUSION: Anaemia was more frequent in patients with active disease and in
      those on corticosteroids. The treatment of anaemia still seems undervalued,
      whereas more than half of anaemic patients were not receiving any specific
      treatment and the use of oral iron prevails contrarily to current
      recommendations.

PMID- 27022723
TI  - Endoscopic band ligation without resection in selected patients for small and
      superficial upper gastrointestinal tract lesions.
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the efficacy of
      endoscopic band ligation (EBL) in carefully selected patients who would benefit
      from this method of resection. METHODS: Patients with early upper
      gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette(r) Multi
      Band Mucosectomy) were prospectively recruited and retrospectively analyzed
      between 2010 and 2015. All cases were discussed in a multidisciplinary cancer
      committee and it was concluded that, owing to patient conditions, surgery was not
      possible and that not conducting histology would not change the clinical
      management. A first endoscopic control with biopsies was planned at 4-8 weeks. If
      there was no persistence of the lesion, new controls were programmed at 6 and 12
      months. RESULTS: The group (n = 12) included 5 esophagus lesions (adenosquamous
      carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric
      lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor
      [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was
      9.6 +/- 2.8 mm (range 4-15). Only one minor adverse event was described. At first
      follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological
      remission, respectively. At 6-month follow-up there was 70% of both endoscopic
      remission and negative biopsies. And at 12 months, there was 100% and 75% of
      endoscopic and histological remission, respectively. Persisting lesions were T1
      cancers. The median follow-up was 30.6 months. CONCLUSION: EBL without resection
      is an easy and safe technique that should be considered in patients with multiple
      morbidities and small superficial UGI lesions.

PMID- 27022725
TI  - Optical Coherence Tomography Angiography of Mixed Neovascularizations in Age
      Related Macular Degeneration.
AB  - PURPOSE: To describe the imaging of mixed neovascular age-related macular
      degeneration (AMD) using optical coherence tomography angiography (OCTA).
      METHODS: Literature review and case series. RESULTS: A review of mixed
      neovascularization in AMD is discussed, focusing on the different subtypes of
      neovascularization and the associated characteristics on imaging, including
      fluorescein angiography, optical coherence tomography, and OCTA. Three cases are
      presented. CONCLUSION: OCTA is a method of identifying mixed neovascularization
      in AMD. Neovascular vessels can be seen on en face images of the retina, both
      below and above the retinal pigment epithelium, corresponding to different types
      of leakage observed on conventional angiography.

PMID- 27022724
TI  - TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair.
AB  - BACKGROUND: Impaired remyelination of demyelinated axons is a major cause of
      neurological disability. In inflammatory demyelinating disease of the central
      nervous system (CNS), although remyelination does happen, it is often incomplete,
      resulting in poor clinical recovery. Poly-IC a known TLR3 agonist and IL-33, a
      cytokine which is induced by poly-IC are known to influence recovery and promote
      repair in experimental models of CNS demyelination. METHODOLOGY AND PRINCIPAL
      FINDINGS: We examined the effect of addition of poly-IC and IL-33 on the
      differentiation and maturation of oligodendrocyte precursor cells (OPC) cultured
      in vitro. Both Poly-IC and IL-33 induced transcription of myelin genes and the
      differentiation of OPC to mature myelin forming cells. Poly-IC induced IL-33 in
      OPC and addition of IL-33 to in vitro cultures, amplified further, IL-33
      expression suggesting an autocrine regulation of IL-33. Poly-IC and IL-33 also
      induced phosphorylation of p38MAPK, a signaling molecule involved in myelination.
      Following the induction of gliotoxic injury with lysolecithin to the corpus
      callosum (CC), treatment of animals with poly-IC resulted in greater recruitment
      of OPC and increased staining for myelin in areas of demyelination. Also, poly-IC
      treated animals showed greater expression of IL-33 and higher expression of M2
      phenotype macrophages in the CC. CONCLUSION/SIGNIFICANCE: Our studies suggest
      that poly-IC and IL-33 play a role in myelin repair by enhancing expression of
      myelin genes and are therefore attractive therapeutic agents for use as
      remyelinating agents in human demyelinating disease.

PMID- 27022726
TI  - Combined Effects of Temperature and Seston Concentration on the Physiological
      Energetics of the Manila Clam Ruditapes philippinarum.
AB  - The suspension-feeding Manila clam Ruditapes philippinarum is a native species of
      the western Pacific that is now widely distributed around the globe because of
      its commercial importance. To determine the adaptive physiological responses to
      changing thermal and nutritional conditions, clearance, filtration, feces
      production, ammonium excretion, respiration rates, and scope for growth (SFG)
      were measured in adult clams. The clams were exposed to 24 treatments involving
      the combination of four water temperatures (8, 13, 18, and 23 degrees C) and six
      concentrations of suspended particulate matter (SPM: 9.5 to 350.5 mg L(-1)).
      Physiological rates were standardized by using the mean (480 mg) of tissue dry
      weights of experimental clams using allometric equations between physiological
      variables and tissue dry weight. Higher clearance rates were recorded at higher
      temperatures and lower SPM concentrations, and these rates decreased with
      increasing SPM concentration at individual temperatures. Consumed energy
      increased with increasing temperature and SPM concentration, peaking at around
      100-200 mg L(-1) at 18-23 degrees C. Whereas fecal energy was largely determined
      by SPM concentration, ammonia excretion was mainly governed by temperature.
      Respiration rate studies revealed a predominant quadratic effect of temperature
      on the metabolism, indicating a lack of acclimatory adjustment of metabolic rate
      to rising temperature. SFG values were positive under almost all the treatment
      conditions and were much higher at higher SPM concentrations (> 45 mg L(-1)),
      with the highest level being recorded at 18 degrees C and 100-200 mg L(-1) SPM.
      Increased filtration rate offset the increased metabolic cost at warm
      temperatures. Our holistic findings suggest that a high degree of physiological
      plasticity allows R. philippinarum to tolerate the wide range of temperatures and
      SPM concentrations that are found in tidal flats, accounting in part for the
      successful distribution of this species over a wide variety of geographical
      areas.

PMID- 27022727
TI  - Effects of Weaning on Intestinal Upper Villus Epithelial Cells of Piglets.
AB  - The intestinal upper villus epithelial cells represent the differentiated
      epithelial cells and play key role in digesting and absorbing lumenal nutrients.
      Weaning stress commonly results in a decrease in villus height and intestinal
      dysfunction in piglets. However, no study have been conducted to test the effects
      of weaning on the physiology and functions of upper villus epithelial cells. A
      total of 40 piglets from 8 litters were weaned at 14 days of age and one piglet
      from each litter was killed at 0 d (w0d), 1 d (w1d), 3 d (w3d), 5 d (w5d), and 7
      d (w7d) after weaning, respectively. The upper villus epithelial cells in mid
      jejunum were isolated using the distended intestinal sac method. The expression
      of proteins in upper villus epithelial cells was analyzed using the isobaric tags
      for relative and absolute quantification or Western blotting. The expression of
      proteins involved in energy metabolism, Golgi vesicle transport, protein amino
      acid glycosylation, secretion by cell, transmembrane transport, ion transport,
      nucleotide catabolic process, translational initiation, and epithelial cell
      differentiation and apoptosis, was mainly reduced during the post-weaning period,
      and these processes may be regulated by mTOR signaling pathway. These results
      indicated that weaning inhibited various cellular processes in jejunal upper
      villus epithelial cells, and provided potential new directions for exploring the
      effects of weaning on the functions of intestine and improving intestinal
      functions in weaning piglets. 

PMID- 27022728
TI  - Combination treatment with herbal medicines and Western medicines in atopic
      dermatitis: Benefits and considerations.
AB  - Herbal medicines (HMs) are often used in combination with Western medicines (WMs)
      to improve therapeutic efficacies of orthodox medicines. This review discussed
      the current status of combination treatment with HMs and WMs in clinical
      practices. The influence of HMs on bioavailability of WMs was also discussed from
      the pharmacokinetic point of view. In addition, benefits and considerations of
      combination treatment were discussed using data obtained from clinical trials and
      randomized controlled trials of HMs treatment in skin diseases. 

PMID- 27022729
TI  - Treatment of fibrillary glomerulonephritis by corticosteroids and tripterygium
      glycoside tablets: A case report.

PMID- 27022731
TI  - Status of Emergency Contraceptives in Europe One Year after the European
      Medicines Agency's Recommendation to Switch Ulipristal Acetate to Non
      Prescription Status.
AB  - BACKGROUND: In November 2014, the European Medicines Agency (EMA) recommended
      switching the emergency contraceptive (EMC) ulipristal acetate to non
      prescription status. This study's objective is to assess the current legal status
      of the two EMCs ulipristal acetate and levonorgestrel in Europe and to report on
      the development of sales figures for EMCs since they were made freely available.
      METHODS: Health authorities were contacted in autumn 2015 and asked about the
      current status of EMCs and whether the sales figures had changed after a switch
      to non-prescription status. Additionally, data on consumption were collected in
      18 German community pharmacies. RESULTS: As of November 2015, most countries in
      the European Union (EU) have followed the EMA recommendation. Hungary kept the
      prescription-only status. In Malta, EMC drugs are not authorized. Germany and
      Croatia switched levonorgestrel to non-prescription status as well. Of the EU
      candidate and European Free Trade Association countries, ulipristal acetate is
      available without prescription in Norway and Bosnia and Herzegovina only. Several
      countries reported an increase in EMC sales since the switch. CONCLUSIONS: An EMA
      recommendation can strongly contribute to the harmonization of a drug's legal
      status in the EU. In most European countries, ulipristal acetate and/or
      levonorgestrel are now freely available.

PMID- 27022730
TI  - Huannao Yicong Decoction () extract reduces inflammation and cell apoptosis in
      Abeta1-42-induced Alzheimer's disease model of rats.
AB  - OBJECTIVE: Huannao Yicong Decoction (, HYD), an effective herbal formula against
      Alzheimer's disease (AD), has been proven to have neuroprotective action in
      amyloid beta-protein1-42 (Abeta1-42)-induced rat model. This study was designed
      to characterize mechanisms by which HYD leads to suppression of inflflammation
      and apoptosis in the brains of Abeta1-42-induced rat. METHODS: A total of 72 rats
      were divided into 6 groups, which were referred to as: sham operation group,
      model group, donepezil-treated group, HYD low-dose group (HYDL), HYD middle-dose
      group (HYDM) and HYD high-dose group (HYDH). Rats in HYDL, HYDM and HYDH were
      injected with Abeta1-42 at the CA1 region of hippocampus to form AD model and
      were fed the HYD extract at different dose of 3.78, 7.56 and 18.90 g crude
      drug/kg. The behavioral changes of rats were evaluated by Morris water maze (MWM)
      before sacrififice. Pathological changes of the brain tissue were evaluated using
      hematoxylin eosin (HE) staining. The levels of interleukin-1 (IL-1) and tumor
      necrosis factor-alpha (TNF-alpha) were measured by radioimmunoassay. The levels
      of Abeta and proteins that are associated with apoptosis such as B-cell lymphoma
      2 protein (Bcl-2), Bcl-2-associated X protein (Bax), cysteine-aspartic protease
      (caspase)-3, -8, -9 and -12 in serum were measured by immunohistochemistry.
      RESULTS: Compared with the sham operation group, the spatial learning and memory
      abilities of AD rats were signifificantly decreased (P<0.05 or P<0.01;
      Expressions of IL-1, TNF-alpha, Abeta and apoptosis-signaling proteins caspase-3,
      -8, -9, -12 were signifificantly up-regulated (P<0.05 or P<0.01). The ratio of
      Bcl-2 to Bax were signifificantly decreased in the model group (P<0.01). When
      treated with HYD extract, the spatial learning and memory abilities of AD-model
      rats were significantly increased (P<0.05 or P<0.01), IL-1, TNF-alpha, Abeta,
      caspase-3, -8, -9 and -12 were down-regulated (P<0.05 or P<0.01), and the ratio
      of Bcl-2 to Bax were reduced (P<0.05 or P<0.01). CONCLUSIONS: HYD extract can
      improve the learning and memory ability defificits, alleviate the inflflammatory
      response and pathological manifestations induced by Abeta1-42 injection in the
      rat model of AD. HYD down-regulates the levels of IL-1, TNF-alpha and Abeta, and
      decreases the rate of apoptosis by modulating apoptosis-signaling-related
      proteins such as caspase-3, -8, -9, and -12.

PMID- 27022732
TI  - Top-Down Nanofabrication and Characterization of 20 nm Silicon Nanowires for
      Biosensing Applications.
AB  - A top-down nanofabrication approach is used to develop silicon nanowires from
      silicon-on-insulator (SOI) wafers and involves direct-write electron beam
      lithography (EBL), inductively coupled plasma-reactive ion etching (ICP-RIE) and
      a size reduction process. To achieve nanometer scale size, the crucial factors
      contributing to the EBL and size reduction processes are highlighted. The
      resulting silicon nanowires, which are 20 nm in width and 30 nm in height (with a
      triangular shape) and have a straight structure over the length of 400 MUm, are
      fabricated precisely at the designed location on the device. The device is
      applied in biomolecule detection based on the changes in drain current (Ids),
      electrical resistance and conductance of the silicon nanowires upon hybridization
      to complementary target deoxyribonucleic acid (DNA). In this context, the scaled
      down device exhibited superior performances in terms of good specificity and high
      sensitivity, with a limit of detection (LOD) of 10 fM, enables for efficient
      label-free, direct and higher-accuracy DNA molecules detection. Thus, this
      silicon nanowire can be used as an improved transducer and serves as novel
      biosensor for future biomedical diagnostic applications. 

PMID- 27022733
TI  - A rare case of pseudotumor formation associated with methyl methacrylate
      hypersensitivity in a patient following cemented total knee arthroplasty.
AB  - Hypersensitivity to orthopedic implant materials has been well documented with
      potential catastrophic consequences if not addressed pre-operatively. The
      spectrum of reactions is wide, from mild non-specific pain with localized
      erythema to severe periprosthetic inflammatory destruction and pseudotumor
      formation. It is therefore essential to identify patients who have or are at risk
      for implant-associated hypersensitivity. Although metal sensitivity is commonly
      cited as the cause of these reactions, methyl methacrylate (MMA) has rarely been
      implicated. To the best of our knowledge, methyl methacrylate-associated
      pseudotumor formation has not yet been described. The following is a case report
      of a 68-year-old female who, after undergoing a routine cemented right total knee
      arthroplasty, developed a painless, enlarging mass during a 13-year period. This
      mass was found to be a pseudotumor in association with methyl methacrylate
      hypersensitivity. A review of pseudotumor pathogenesis, methyl methacrylate
      hypersensitivity, and preoperative preventative care is discussed. 

PMID- 27022734
TI  - Viscosity-adjusted estimation of pressure head and pump flow with quasi-pulsatile
      modulation of rotary blood pump for a total artificial heart.
AB  - Estimation of pressure and flow has been an important subject for developing
      implantable artificial hearts. To realize real-time viscosity-adjusted estimation
      of pressure head and pump flow for a total artificial heart, we propose the table
      estimation method with quasi-pulsatile modulation of rotary blood pump in which
      systolic high flow and diastolic low flow phased are generated. The table
      estimation method utilizes three kinds of tables: viscosity, pressure and flow
      tables. Viscosity is estimated from the characteristic that differential value in
      motor speed between systolic and diastolic phases varies depending on viscosity.
      Potential of this estimation method was investigated using mock circulation
      system. Glycerin solution diluted with salty water was used to adjust viscosity
      of fluid. In verification of this method using continuous flow data, fairly good
      estimation could be possible when differential pulse width modulation (PWM) value
      of the motor between systolic and diastolic phases was high. In estimation under
      quasi-pulsatile condition, inertia correction was provided and fairly good
      estimation was possible when the differential PWM value was high, which was not
      different from the verification results using continuous flow data. In the
      experiment of real-time estimation applying moving average method to the
      estimated viscosity, fair estimation could be possible when the differential PWM
      value was high, showing that real-time viscosity-adjusted estimation of pressure
      head and pump flow would be possible with this novel estimation method when the
      differential PWM value would be set high. 

PMID- 27022735
TI  - Imaging Features of Pulmonary CT in Type 2 Diabetic Patients with Multidrug
      Resistant Tuberculosis.
AB  - BACKGROUND: Until now, radiographic manifestations of multidrug-resistant
      pulmonary tuberculosis (MDR- TB) in patients with diabetes mellitus (DM) have not
      been reported. We conducted a study to investigate the imaging features of
      pulmonary computed tomography (CT) for type 2 diabetic (T2DM) patients with MDR
      TB. METHODS: The clinical data and pulmonary CT findings of 39 type 2 diabetic
      patients with MDR-TB, 46 type 2 diabetic patients with drug-susceptible
      tuberculosis (DS-TB), and 72 pure drug-susceptible TB cases (without T2DM and
      MDR) treated at Dalian Tuberculosis Hospital from 2012 to 2015 were collected,
      and the clinical features and imaging differences of the three groups were
      compared. RESULTS: The clinical characteristics of the three groups of patients
      were not significantly different except with respect to age and previous
      treatment history. However, on imaging, the patients with MDR-TB showed
      consolidation in and above the pulmonary segments was significantly more
      extensive than that seen in the DS-TB group with or without T2DM. CONCLUSION:
      Consolidation in or above multiple pulmonary segments with multiple mouth-eaten
      cavities and bronchial damage on pulmonary CT images in type 2 diabetic patients
      with tuberculosis suggests the possibility of multi-drug resistance.

PMID- 27022736
TI  - Interleukin-22 promotes papillary thyroid cancer cell migration and invasion
      through microRNA-595/Sox17 axis.
AB  - Interleukin-22 (IL-22) is an inflammatory cytokine mainly produced by activated
      Th17 and Th22 cells. The data presented here demonstrate that IL-22 induced the
      migration and invasion of papillary thyroid cancer (PTC) cells. MicroRNA
      expression analysis and functional studies indicated that IL-22-mediated
      migration and invasion is positively regulated by miR-595. Further mechanistic
      studies revealed that sex-determining region Y-box 17 (Sox17) is directly
      targeted by miR-595. We then demonstrated that IL-22 regulated migration and
      invasion of PTC cells via inhibiting Sox17 expression. Interestingly, in PTC cell
      lines and PTC tissues, expression of IL-22 and miR-595 was upregulated and Sox17
      downregulated compared with normal thyroid, and their expression levels were
      closely correlated. Taken together, this present study suggests that IL-22
      stimulation enhances the migration and invasion of PTC cells by regulating miR
      595 and its target Sox17.

PMID- 27022737
TI  - Long noncoding RNA FGFR3-AS1 promotes osteosarcoma growth through regulating its
      natural antisense transcript FGFR3.
AB  - Long noncoding RNAs (lncRNAs), a new class of RNAs with no protein-coding
      potential, have been reported to have crucial roles in the regulation of a
      variety of tumors. However, the functions and molecular mechanisms of lncRNAs to
      osteosarcoma are still largely unknown. The purpose of this study is to examine
      the expression, functions and molecular mechanisms of a new lncRNA FGFR3
      antisense transcript 1 (FGFR3-AS1) in osteosarcoma. The expression of FGFR3-AS1
      was examined by real-time quantitative PCR. The regulation of FGFR3 by FGFR3-AS1
      was examined by RNase protection assay, real-time quantitative PCR, western
      blotting, and luciferase reporter assay. The effects of FGFR3-AS1 on osteosarcoma
      cell proliferation and cell cycle were determined by Cell Counting Kit-8, Ethynyl
      deoxyuridine incorporation assay and flow cytometry. FGFR3-AS1 was upregulated in
      osteosarcoma. Increased FGFR3-AS1 expression correlates with large tumor size,
      advanced Enneking stage, metastasis and poor survival. Through antisense pairing
      with FGFR3 3'UTR, FGFR3-AS1 increases FGFR3 mRNA stability and upregulates FGFR3
      expression. The expression of FGFR3-AS1 and FGFR3 is positively correlated in
      osteosarcoma tissues. Knockdown of FGFR3-AS1 inhibits the proliferation and cell
      cycle progression of osteosarcoma cells in vitro. Moreover, knockdown of FGFR3
      AS1 inhibits xenograft tumor growth of osteosarcoma cells in vivo. These data
      demonstrate the mechanisms of how antisense noncoding RNA regulate the expression
      of sense genes, and show the pivotal functions of FGFR3-AS1 in osteosarcoma. 

PMID- 27022739
TI  - The Community As the Patient in Malaria-Endemic Areas: Preempting Drug Resistance
      with Multiple First-Line Therapies.
AB  - Maciej F. Boni and colleagues propose deploying multiple first-line combination
      therapies against malaria within a community to delay drug-resistance evolution. 

PMID- 27022740
TI  - Disaggregating Tropical Disease Prevalence by Climatic and Vegetative Zones
      within Tropical West Africa.
AB  - Tropical infectious disease prevalence is dependent on many socio-cultural
      determinants. However, rainfall and temperature frequently underlie overall
      prevalence, particularly for vector-borne diseases. As a result these diseases
      have increased prevalence in tropical as compared to temperate regions. Specific
      to tropical Africa, the tendency to incorrectly infer that tropical diseases are
      uniformly prevalent has been partially overcome with solid epidemiologic data.
      This finer resolution data is important in multiple contexts, including
      understanding risk, predictive value in disease diagnosis, and population
      immunity. We hypothesized that within the context of a tropical climate, vector
      borne pathogen prevalence would significantly differ according to zonal
      differences in rainfall, temperature, relative humidity and vegetation condition.
      We then determined if these environmental data were predictive of pathogen
      prevalence. First we determined the prevalence of three major pathogens of
      cattle, Anaplasma marginale, Babesia bigemina and Theileria spp, in the three
      vegetation zones where cattle are predominantly raised in Ghana: Guinea savannah,
      semi-deciduous forest, and coastal savannah. The prevalence of A. marginale was
      63%, 26% for Theileria spp and 2% for B. bigemina. A. marginale and Theileria
      spp. were significantly more prevalent in the coastal savannah as compared to
      either the Guinea savanna or the semi-deciduous forest, supporting acceptance of
      the first hypothesis. To test the predictive power of environmental variables,
      the data over a three year period were considered in best subsets multiple linear
      regression models predicting prevalence of each pathogen. Corrected Akaike
      Information Criteria (AICc) were assigned to the alternative models to compare
      their utility. Competitive models for each response were averaged using AICc
      weights. Rainfall was most predictive of pathogen prevalence, and EVI also
      contributed to A. marginale and B. bigemina prevalence. These findings support
      the utility of environmental data for understanding vector-borne disease
      epidemiology on a regional level within a tropical environment. 

PMID- 27022741
TI  - Propensity Score-Based Approaches to Confounding by Indication in Individual
      Patient Data Meta-Analysis: Non-Standardized Treatment for Multidrug Resistant
      Tuberculosis.
AB  - BACKGROUND: In the absence of randomized clinical trials, meta-analysis of
      individual patient data (IPD) from observational studies may provide the most
      accurate effect estimates for an intervention. However, confounding by indication
      remains an important concern that can be addressed by incorporating individual
      patient covariates in different ways. We compared different analytic approaches
      to account for confounding in IPD from patients treated for multi-drug resistant
      tuberculosis (MDR-TB). METHODS: Two antibiotic classes were evaluated,
      fluoroquinolones--considered the cornerstone of effective MDR-TB treatment--and
      macrolides, which are known to be safe, yet are ineffective in vitro. The primary
      outcome was treatment success against treatment failure, relapse or death. Effect
      estimates were obtained using multivariable and propensity-score based
      approaches. RESULTS: Fluoroquinolone antibiotics were used in 28 included
      studies, within which 6,612 patients received a fluoroquinolone and 723 patients
      did not. Macrolides were used in 15 included studies, within which 459 patients
      received this class of antibiotics and 3,670 did not. Both standard multivariable
      regression and propensity score-based methods resulted in similar effect
      estimates for early and late generation fluoroquinolones, while macrolide
      antibiotics use was associated with reduced treatment success. CONCLUSIONS: In
      this individual patient data meta-analysis, standard multivariable and propensity
      score based methods of adjusting for individual patient covariates for
      observational studies yielded produced similar effect estimates. Even when
      adjustment is made for potential confounding, interpretation of adjusted
      estimates must still consider the potential for residual bias.

PMID- 27022742
TI  - Bacillus bombysepticus alpha-Toxin Binding to G Protein-Coupled Receptor Kinase 2
      Regulates cAMP/PKA Signaling Pathway to Induce Host Death.
AB  - Bacterial pathogens and their toxins target host receptors, leading to aberrant
      behavior or host death by changing signaling events through subversion of host
      intracellular cAMP level. This is an efficient and widespread mechanism of
      microbial pathogenesis. Previous studies describe toxins that increase cAMP in
      host cells, resulting in death through G protein-coupled receptor (GPCR)
      signaling pathways by influencing adenylyl cyclase or G protein activity. G
      protein-coupled receptor kinase 2 (GRK2) has a central role in regulation of GPCR
      desensitization. However, little information is available about the pathogenic
      mechanisms of toxins associated with GRK2. Here, we reported a new bacterial
      toxin-Bacillus bombysepticus (Bb) alpha-toxin that was lethal to host. We showed
      that Bb alpha-toxin interacted with BmGRK2. The data demonstrated that Bb alpha
      toxin directly bound to BmGRK2 to promote death by affecting GPCR signaling
      pathways. This mechanism involved stimulation of Galphas, increase level of cAMP
      and activation of protein kinase A (PKA). Activated cAMP/PKA signal transduction
      altered downstream effectors that affected homeostasis and fundamental biological
      processes, disturbing the structural and functional integrity of cells, resulting
      in death. Preventing cAMP/PKA signaling transduction by inhibitions (NF449 or H
      89) substantially reduced the pathogenicity of Bb alpha-toxin. The discovery of a
      toxin-induced host death specifically linked to GRK2 mediated signaling pathway
      suggested a new model for bacterial toxin action. Characterization of host genes
      whose expression and function are regulated by Bb alpha-toxin and GRK2 will offer
      a deeper understanding of the pathogenesis of infectious diseases caused by
      pathogens that elevate cAMP. 

PMID- 27022743
TI  - Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by
      opsonization of endogenous antigen.
AB  - In the pathogenesis of central nervous system (CNS) demyelinating disorders,
      antigen-specific B cells are implicated to act as potent antigen-presenting cells
      (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the
      first evidence that CNS-reactive antibodies (Ab) are similarly capable of
      initiating an encephalitogenic immune response by targeting endogenous CNS
      antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive
      production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient
      to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the
      absence of B cells, when mice endogenously contained MOG-recognizing T cells.
      Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and
      expansion of peripheral MOG-specific T cells in an Fc-dependent manner,
      subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were
      added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise
      undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of
      intact MOG; internalized, processed and presented MOG activated naive T cells to
      differentiate in an encephalitogenic manner. In a series of translational
      experiments, anti-MOG Ab from two patients with an acute flare of CNS
      inflammation likewise facilitated detection of human MOG. Jointly, these
      observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as
      a novel disease- and/or relapse-triggering mechanism in CNS demyelinating
      disorders.

PMID- 27022744
TI  - Analysis of Soluble Molecular Fibronectin-Fibrin Complexes and EDA-Fibronectin
      Concentration in Plasma of Patients with Atherosclerosis.
AB  - Atherosclerosis, a chronic vascular disease, leads to molecular events bound with
      interplaying processes of inflammation and coagulation. In the present study,
      fibronectin (FN), FN containing extra domain A (EDA-FN), frequency of occurrence,
      and relative amounts of soluble plasma FN-fibrin complexes were analyzed in 80
      plasma samples of patients suspected of coronary artery disease based on clinical
      evaluation and changes in arteries found by computed tomographic coronary
      angiography. The study showed that in the plasma of the patients' group with high
      risk of coronary artery disease EDA-FN concentration was significantly higher
      (3.5 +/- 2.5 mg/L; P < 0.025) and the molecular FN-fibrin complexes of 1000 kDa
      and higher occurred more often than in the groups of patients with mild risk of
      coronary artery disease and the normal age-matched. The increased level of EDA-FN
      and occurrence of FN-fibrin complexes could have a potential diagnostic value in
      the diagnosis and management of patients with coronary artery disease. 

PMID- 27022745
TI  - Interaction between STAT3 gene polymorphisms and smoking on Crohn's disease
      susceptibility: a case-control study in a Chinese Han population.
AB  - AIMS: The aim of this study was to investigate the impact of the signal
      transducer and activator of transcription 3 (STAT3) gene and additional STAT3
      gene-smoking interaction on Crohn's disease (CD) risk based on a Chinese
      population. METHODS: A total of 1012 participants (491 men, 521 women), were
      selected, including 502 CD patients and 510 normal controls. The mean age of all
      participants was 42.3 +/- 11.2 years. Logistic regression model was used to
      examine the association between single nucleotide polymorphism (SNP) of STAT3 and
      CD risk; the odds ratio (OR) and 95 % confident interval (95 % CI) were
      calculated. Generalized multifactor dimensionality reduction was employed to
      analyze the interaction among several SNPs. RESULTS: Logistic analysis showed the
      significant association between genotypes of variants in two SNP and decreased CD
      risk, after covariates adjustment. The carriers of homozygous mutant of two SNP
      polymorphism revealed decreased CD risk than those with wild-type homozygotes; OR
      (95 % CI) was 0.75 (0.59-0.93) and 0.68 (0.57-0.91), respectively. There was a
      significant two-locus model (p = 0.0107) involving rs744166 and smoking,
      indicating a potential gene-environment interaction between rs744166 and smoking.
      Overall, the cross-validation consistency was 10/10, and the testing accuracy was
      62.17 %, and never smokers with TC or CC genotype have the lowest CD risk,
      compared to smokers with TT genotype; OR (95 % CI) was 0.52 (0.31-0.82), after
      covariate adjustment. CONCLUSIONS: Our results support an important association
      of rs744166 and rs4796793 with decreased CD risk, and additional interaction
      between rs744166 and smoking.

PMID- 27022746
TI  - Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells.
AB  - Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic
      epithelial cells (mTECs) is crucial for negative selection of self-reactive T
      cells to establish central tolerance. Intercellular transfer of self-peptide-MHC
      complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs,
      which in turn contributes to negative selection and regulatory T cell generation.
      However, mTECs are unlikely to express all TRAs, such as immunoglobulins
      generated only in B cells after somatic recombination, hyper-mutation, or class
      switches. We report here that both mTECs and cortical TECs can efficiently
      acquire not only cell surface but also intracellular proteins from thymocytes.
      This reveals a previously unappreciated intercellular sharing of molecules from
      thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing
      a full spectrum of central tolerance. 

PMID- 27022748
TI  - INTERNATIONAL SOCIETY OF PHARMACOVIGILANCE : ABSTRACTS.

PMID- 27022747
TI  - Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural
      differentiation by modulating the let-7a-Lin28 signaling pathway.
AB  - The commonly used inhalational anesthetic, sevoflurane, can cause toxicity to the
      central nervous system of the developing fetus. Lin28 has been reported to
      regulate let-7a, thereby modulating embryo development, neurodegeneration, and
      even neuron-related tumorigenesis. We demonstrate that pregnant mice receiving
      sevoflurane treatment during the early stage of pregnancy give birth to fewer
      offspring presenting a lower birth weight. We have also treated mouse embryonic
      stem cells (mESCs) with sevoflurane for 6 h and determined that mESCs self
      renewal is repressed, and that differentiation is initiated earlier than in
      controls. We have induced neural differentiation in the treated mESCs and
      determined that their neurogenesis is weakened. Furthermore, sevoflurane
      upregulates the level of let-7a, which might repress mESC self-renewal by
      directly targeting the Lin28 3'-untranslated region. Lin28 overexpression
      attenuates the influence of sevoflurane or of let-7a on the self-renewal of mESCs
      and their subsequent neural differentiation. The let-7a inhibitor also abolishes
      the influence of sevoflurane. Thus, the let-7a-Lin28 pathway is involved in the
      sevoflurane-induced inhibition of ESC self-renewal and subsequent neurogenesis.
      Our study demonstrates the molecular mechanism underlying the side effects of
      sevoflurane during early development, laying the foundation for studies on the
      safe and reasonable usage of other inhalational anesthetics.

PMID- 27022749
TI  - Communication at the Garden Fence--Context Dependent Vocalization in Female House
      Mice.
AB  - House mice (Mus musculus) live in social groups where they frequently interact
      with conspecifics, thus communication (e.g. chemical and/or auditory) is
      essential. It is commonly known that male and female mice produce complex
      vocalizations in the ultrasonic range (USV) that remind of high-pitched birdsong
      (so called mouse song) which is mainly used in social interactions. Earlier
      studies suggest that mice use their USVs for mate attraction and mate choice, but
      they could also be used as signal during hierarchy establishment and
      familiarization, or other communication purposes. In this study we elucidated the
      vocalization behaviour of interacting female mice over an extended period of time
      under semi-natural conditions. We asked, if the rate or structure of female
      vocalization differs between different social and non-social contexts. We found
      that female USV is mainly used in social contexts, driven by direct communication
      to an unknown individual, the rate of which is decreased over time by a
      familiarization process. In addition we could show that female mice use two
      distinct types of USVs, differing in their frequency, which they use differently
      depending on whether they directly or indirectly communicate with another female.
      This supports the notion that vocalization in mice is context dependent, driven
      by a reasonable and yet underestimated amount of complexity that also involves
      the interplay between different sensory signals, like chemical and auditory cues.

PMID- 27022750
TI  - Bovine Lactoferrampin, Human Lactoferricin, and Lactoferrin 1-11 Inhibit Nuclear
      Translocation of HIV Integrase.
AB  - This study aimed to investigate fragments derived from human and bovine
      lactoferrins for ability to inhibit nuclear translocation of HIV-1 integrase. It
      was shown that human lactoferricin, human lactoferrin 1-11, and bovine
      lactoferrampin reduced nuclear distribution of HIV-1 integrase. Bovine
      lactoferrampin could inhibit both the activity and nuclear translocation of HIV-1
      integrase. Human lactoferrampin, bovine lactoferricin, and bovine lactoferrin 1
      11 had no effect on HIV-1 integrase nuclear translocation. Human lactoferrampin
      which inhibited the activity of integrase did not prevent its nuclear
      translocation. Human lactoferricin and lactoferrin 1-11 did not inhibit HIV-1
      integrase nuclear translocation despite their ability to attenuate the enzyme
      activity. The discrepancy between the findings on reduction of HIV-1 activity and
      inhibition of nuclear translocation of HIV-1 integrase was due to the different
      mechanisms involved. A similar reasoning can also be applied to the different
      inhibitory potencies of the milk peptides on different HIV enzymes, i.e., nuclear
      translocation. 

PMID- 27022751
TI  - The Online Morphology Control and Dynamic Studies on Improving Vitamin B12
      Production by Pseudomonas denitrificans with Online Capacitance and Specific
      Oxygen Consumption Rate.
AB  - The relationship between the morphological character of Pseudomonas denitrificans
      and vitamin B12 synthesis based on real-time capacitance measurement and online
      specific oxygen consumption rate (Q O2) control was established for enhancing
      vitamin B12 production. Results demonstrated that the threshold Q O2 value lower
      than 2.0 mmol/gDCW/l would greatly stimulate the state transfer from the cell
      number growth phase to the cell elongation phase and promote rapid vitamin B12
      biosynthesis, while the vitamin B12 biosynthesis rate could also be inhibited
      when the rate of cell's length-to-width ratio (ratio-LW) was higher than 10:1.
      Furthermore, the optimal morphology controlling strategy was achieved based on
      online Q O2 control, which increases the appropriate active cell numbers at the
      former phase, and then control the elongation of ratio-LW no more than 10:1 at
      the vitamin B12 biosynthesis phase. The maximal vitamin B12 production reached
      239.7 mg/l at 168 h, which was improved by 14.7 % compared with the control (208
      mg/l). This online controlling strategy would be effectively applied for
      improving industrial vitamin B12 fermentation. 

PMID- 27022752
TI  - The validity of student tutors' judgments in early detection of struggling in
      medical school. A prospective cohort study.
AB  - Early identification and support of strugglers in medical education is generally
      recommended in the research literature, though very little evidence of the
      diagnostic qualities of early teacher judgments in medical education currently
      exists. The aim of this study was to examine the validity of early diagnosis of
      struggling in medical school based on informal teacher judgements of in-class
      behavior. The study design was a prospective cohort study and the outcomes/truth
      criteria were anatomy failure and medical school drop out. Six weeks into an
      anatomy course, student tutors attempted to identify medical students, who they
      reckoned would fail the anatomy course or drop out, based on their everyday
      experiences with students in a large group educational setting. In addition, they
      were asked to describe the indicators of struggling they observed. Sixteen
      student tutors evaluated 429 medical students for signs of struggling. By week
      six, the student tutors were able to detect approximately 1/4-1/3 of the students
      who eventually failed or dropped out, and for 3/4 of the strugglers they
      identified, they were correct in their judgments. Informal student tutor's
      judgements showed incremental validity for both outcomes when controlling for
      grades obtained in preceeding exams. Lack of participation, lack of commitment,
      poor academic performance, poor social interactions and general signs of distress
      were the main indicators of struggling identified. Teachers' informal judgements
      of in-class behavior may be an untapped source of information in the early
      identification of struggling medical students with added value above and beyond
      formal testing.

PMID- 27022753
TI  - Optical Coherence Tomography Angiography of Deep Capillary Ischemia.
AB  - Paracentral acute middle maculopathy (PAMM) is defined by the spectral-domain
      optical coherence tomography (OCT) finding of paracentral hyper-reflective band
      like lesions of the inner nuclear layer (INL) of the macula that progress to
      corresponding areas of severe INL thinning. En face analysis has enabled more
      detailed analyses and quantifications of these lesions and has provided insights
      into the pathogenesis of this abnormality. While there is a wealth of demographic
      and anatomical data indicating that these PAMM lesions are the result of an INL
      infarct, OCT angiography is the first modality to provide direct evidence.
      Several studies have recently shown that old PAMM lesions are indeed associated
      with ischemia of the deep capillary retinal plexus, while acute lesions may or
      may not show initial perfusion of the deep capillary retinal plexus. 

PMID- 27022754
TI  - Synchronous uterine adenocarcinoma and leiomyosarcoma: A rare case report causing
      a clinical conundrum.
AB  - INTRODUCTION: Synchronous gynecologic primary cancers are uncommon. When present,
      the most frequent malignancies consist of endometrial and ovarian carcinomas.
      Here we report an exceedingly rare case of concurrent uterine adenocarcinoma and
      leiomyosarcoma. CASE PRESENTATION: A 60 year-old female presented with four years
      of postmenopausal bleeding. An endometrial sampling showed grade 2 endometrioid
      adenocarcinoma. She proceeded with hysterectomy that contained an anterior
      endometrial mass and a posterior myometrial mass. The final pathology
      demonstrated concurrent uterine adenocarcinoma and leiomyosarcoma. DISCUSSION: To
      the best of our knowledge, this is the third reported case of simultaneous
      uterine adenocarcinoma and leiomyosarcoma. As this presentation is infrequent
      with limited literature, this caused a clinical management conundrum.
      Unfortunately, the follow-up PET scan suggested possible recurrence or metastasis
      three months after the surgery. CONCLUSION: Simultaneous uterine adenocarcinoma
      and leiomyosarcoma is an exceptionally rare event. As the experience is limited,
      a multidisciplinary approach in managing these patients may be the best option
      currently available.

PMID- 27022755
TI  - Acoustically Propelled Nanomotors for Intracellular siRNA Delivery.
AB  - An effective intracellular gene silencing strategy based on acoustically
      propelled nanowires modified with an interfering RNA's (siRNA) payload is
      described. The gold nanowires (AuNW) are wrapped with a Rolling Circle
      Amplification (RCA) DNA strand, which serves to anchor the siRNA therapy. The
      ultrasound (US)-powered propulsion of the AuNW leads to fast internalization and
      rapid intracellular movement and hence to an accelerated siRNA delivery and
      silencing response. To optimize the micromotor gene silencing procedure, the
      influence of motion, time, and siRNA dosage was investigated, leading up to a 94%
      silencing after few minutes treatment with US-propelled siRNA-AuNWs, and to a
      dramatic (~13-fold) improvement in the silencing response compared to the static
      modified nanowires. The ability of the nanomotor-based method for gene silencing
      has been demonstrated by measuring the GFP silencing response in two different
      cell lines (HEK-293 and MCF-7) and using detailed control experiments. The
      viability of the cells after the nanomotors treatment was examined using the MCF
      7 cancer cell line. The use of DNA structures carried by the US-propelled
      nanomotors for gene silencing represents an efficient tool that addresses the
      challenges associated with RNA transportation and intracellular delivery. Future
      implementation of nanomachines in gene therapy applications can be expanded into
      a co-delivery platform for therapeutics.

PMID- 27022756
TI  - A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors.
AB  - The analysis of receptor tyrosine kinases and their interacting ligands involved
      in vascular biology is often challenging due to the constitutive expression of
      families of related receptors, a broad range of related ligands and the
      difficulty of dealing with primary cultures of specialized endothelial cells.
      Here we describe a bioassay for the detection of ligands to the vascular
      endothelial growth factor receptor-2 (VEGFR-2), a key transducer of signals that
      promote angiogenesis and lymphangiogenesis. A cDNA encoding a fusion of the
      extracellular (ligand-binding) region of VEGFR-2 with the transmembrane and
      cytoplasmic regions of the erythropoietin receptor (EpoR) is expressed in the
      factor-dependent cell line Ba/F3. This cell line grows in the presence of
      interleukin-3 (IL-3) and withdrawal of this factor results in death of the cells
      within 24 hr. Expression of the VEGFR-2/EpoR receptor fusion provides an
      alternative mechanism to promote survival and potentially proliferation of stably
      transfected Ba/F3 cells in the presence of a ligand capable of binding and cross
      linking the extracellular portion of the fusion protein (i.e., one that can cross
      link the VEGFR-2 extracellular region). The assay can be performed in two ways: a
      semi-quantitative approach in which small volumes of ligand and cells permit a
      rapid result in 24 hr, and a quantitative approach involving surrogate markers of
      a viable cell number. The assay is relatively easy to perform, is highly
      responsive to known VEGFR-2 ligands and can accommodate extracellular inhibitors
      of VEGFR-2 signaling such as monoclonal antibodies to the receptor or ligands,
      and soluble ligand traps. 

PMID- 27022757
TI  - Selective Cell Elimination from Mixed 3D Culture Using a Near Infrared
      Photoimmunotherapy Technique.
AB  - Recent developments in tissue engineering offer innovative solutions for many
      diseases. For example, tissue engineering using induced pluripotent stem cell
      (iPS) emerged as a new method in regenerative medicine. Although this tissue
      regeneration is promising, contamination with unwanted cells during tissue
      cultures is a major concern. Moreover, there is a safety concern regarding
      tumorigenicity after transplantation. Therefore, there is an urgent need for
      eliminating specific cells without damaging other cells that need to be
      protected, especially in established tissue. Here, we present a method for
      specific cell elimination from a mixed 3D cell culture in vitro with near
      infrared photoimmunotherapy (NIR-PIT) without damaging non-targeted cells. This
      technique enables the elimination of specific cells from mixed cell cultures or
      tissues. 

PMID- 27022758
TI  - A Simplified Method for Ultra-Low Density, Long-Term Primary Hippocampal Neuron
      Culture.
AB  - Culturing primary hippocampal neurons in vitro facilitates mechanistic
      interrogation of many aspects of neuronal development. Dissociated embryonic
      hippocampal neurons can often grow successfully on glass coverslips at high
      density under serum-free conditions, but low density cultures typically require a
      supply of trophic factors by co-culturing them with a glia feeder layer,
      preparation of which can be time-consuming and laborious. In addition, the
      presence of glia may confound interpretation of results and preclude studies on
      neuron-specific mechanisms. Here, a simplified method is presented for ultra-low
      density (~2,000 neurons/cm2), long-term (>3 months) primary hippocampal neuron
      culture that is under serum free conditions and without glia cell support. Low
      density neurons are grown on poly-D-lysine coated coverslips, and flipped on high
      density neurons grown in a 24-well plate. Instead of using paraffin dots to
      create a space between the two neuronal layers, the experimenters can simply etch
      the plastic bottom of the well, on which the high density neurons reside, to
      create a microspace conducive to low density neuron growth. The co-culture can be
      easily maintained for >3 months without significant loss of low density neurons,
      thus facilitating the morphological and physiological study of these neurons. To
      illustrate this successful culture condition, data are provided to show profuse
      synapse formation in low density cells after prolonged culture. This co-culture
      system also facilitates the survival of sparse individual neurons grown in
      islands of poly-D-lysine substrates and thus the formation of autaptic
      connections.

PMID- 27022759
TI  - Morphological Characterization of ALD and Doping Effects on Mesoporous SnO2
      Aerogels by XPS and Quantitative SEM Image Analysis.
AB  - Atomic layer deposition (ALD) is unsurpassed in its ability to create thin
      conformal coatings over very rough and/or porous materials. Yet although the
      coating thickness on flat surfaces can be measured by ellipsometry,
      characterization of these coatings on rough surfaces is difficult. Here, two
      techniques are demonstrated to provide such characterization of ALD-coated TiO2
      over mesoporous SnO2 aerogel films on glass substrates, and insights are gained
      as to the ALD process. First, X-ray photoelectron spectroscopy (XPS) is used to
      determine the coating thickness over the aerogel, and the results (0.04 nm/cycle)
      agree well with ellipsometry on flat surfaces up to a coating thickness limit of
      about 6 nm. Second, quantitative analysis of SEM images of the aerogel cross
      section is used to determine porosity and roughness, from which coating thickness
      can be inferred. The analysis reveals increasing porosity from the aerogel/air
      interface to the aerogel/substrate interface, indicating a thicker ALD coating
      near the air side, which is consistent with tortuous diffusion through the pores
      limiting access of ALD precursors to deeper parts of the film. SEM-derived
      porosity is generally useful in a thin film because bulk methods like nitrogen
      physisorption or mercury porosimetry are impractical for use with thin-film
      samples. Therefore, in this study SEM was also used to characterize
      quantitatively the morphologogical changes in SnO2 aerogel thin films due to
      doping with Sb. This study can be used as a methodology to understand
      morphological changes in different types of porous and/or rough materials. 

PMID- 27022760
TI  - Geometrical Properties Can Predict CO2 and N2 Adsorption Performance of Metal
      Organic Frameworks (MOFs) at Low Pressure.
AB  - Metal-organic frameworks (MOFs) are nanoporous materials with exceptional host
      guest properties poised for groundbreaking innovations in gas separation
      applications according to high-throughput (HT) screening data. However, MOF
      structural libraries are nearly infinite in practice and so statistical and
      information technology will play a fundamental role in implementing and
      rationalizing MOF virtual screening. In this work, we apply k-means clustering
      and archetypal analysis (AA) to identify the truly significant nanoporous
      structures in a large library of ~82 000 virtual MOFs. Quantitative structure
      property relationship (QSPR) models of the theoretical CO2 and N2 uptake
      capacities were also developed using a calibration set of ~16 000 hypothetical
      MOF structures derived from the prototypes and archetype frameworks. Since uptake
      capacities correlated poorly to the void fraction, surface area and pore size but
      these properties were used to build binary classifier predictors that
      successfully identify "high-performing" nanoporous materials in an external test
      set of ~65 000 MOFs with accuracy higher than 94%. The accuracy of the
      classification decreased for MOFs with fluorine substituents. The classification
      models can serve as efficient filtering tools to detecting promising high
      performing candidates at the early stage of virtual high-throughput screening of
      novel porous materials.

PMID- 27022761
TI  - Insight into the Capacity Fading Mechanism of Amorphous Se2S5 Confined in
      Micro/Mesoporous Carbon Matrix in Ether-Based Electrolytes.
AB  - In contrast to the stable cycle performance of space confined Se-based cathodes
      for lithium batteries in carbonate-based electrolytes, their common capacity
      fading in ether-based electrolytes has been paid less attention and not yet well
      addressed so far. In this work, the lithiation/delithiation of amorphous Se2S5
      confined in micro/mesoporous carbon (Se2S5/MPC) cathode was investigated by in
      situ X-ray near edge absorption spectroscopy (XANES) and theoretical
      calculations. The Se2S5/MPC composite was synthesized by a modified vaporization
      condensation method to ensure a good encapsulation of Se2S5 into the pores of MPC
      host. In situ XANES results illustrated that the lithiation/delithiation
      reversibility of Se component was gradually decreased in ether-based
      electrolytes, leading to an aggravated formation of long-chain polyselenides
      during cycling and further capacity decay. Moreover, ab initio calculations
      revealed that the binding energy of polyselenides (Li2Sen) with carbon host is in
      an order of Li2Se6 > Li2Se4 > Li2Se. The insights into the failure mechanism of
      Se-based cathode gain in this work are expected to serve as a guide for future
      design on high performance Se-based cathodes. 

PMID- 27022762
TI  - Covalent Grafting of Tethered Homopolymer Film on p-Si(100).
AB  - Covalent grafting of a homopolymer film onto a p-Si(100) surface was performed by
      use of surface electroinitiated emulsion polymerization. This polymerization
      method was one-step and cost-effective, and worked in the aqueous dispersed media
      containing both nitrobenzenediazonium (NBD) tetrafluoroborate and methyl
      methacrylate (MMA) monomer. NBD was reduced in the vicinity of substrate at the
      cut-on voltage of the pulsed voltage and was successively grafted on a Si
      surface, leading to a polynitrophenyl (PNP) layer. The reduction of NBD
      simultaneously initiated the polymerization of MMA. The resulting PMMA
      macroradicals in the solution can react with the previously grafted PNP at the
      cutoff voltage of the pulsed voltage for thickening the polymer film. The
      prepared polymer layer completely covered the Si surface, as investigated by the
      scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques.
      Importantly, chemical components and the thickness of the grafted polymer film
      were well controlled by the applied voltage and the charge flow passing through
      the Si electrode. X-ray photoelectron spectroscopy (XPS) measurement further
      confirmed the Si-C bond between the polymer layer and the Si substrate. The
      homopolymer film was extremely effective in protecting the underlying Si from
      atmospheric oxidation. 

PMID- 27022763
TI  - Analyzing the Effects of Climate Factors on Soybean Protein, Oil Contents, and
      Composition by Extensive and High-Density Sampling in China.
AB  - From 2010 to 2013, 763 soybean samples were collected from an extensive area of
      China. The correlations between seed compositions and climate data were analyzed.
      The contents of crude protein and water-soluble protein, total amount of protein
      plus oil, and most of the amino acids were positively correlated with an
      accumulated temperature >=15  degrees C (AT15) and the mean daily temperature
      (MDT) but were negatively correlated with hours of sunshine (HS) and diurnal
      temperature range (DTR). The correlations of crude oil and most fatty acids with
      climate factors were opposite to those of crude protein. Crude oil content had a
      quadratic regression relationship with MDT, and a positive correlation between
      oil content and MDT was found when the daily temperature was <19.7  degrees C. A
      path analysis indicated that DTR was the main factor that directly affected
      soybean protein and oil contents. The study illustrated the effects of climate
      factors on soybean protein and oil contents and proposed agronomic practices for
      improving soybean quality in different regions of China. The results provide a
      foundation for the regionalization of high-quality soybean production in China
      and similar regions in the world. 

PMID- 27022764
TI  - [Systemic lupus erythematosus].
AB  - The management of patients with SLE still brings significant challenges, also on
      intellectual grounds. However, for most of the standard situations, clear
      principles can be delineated for diagnosis and therapy. New drugs and
      international definitions of strategies in SLE patient care constitute
      significant improvement and promise further progress for the coming years. 

PMID- 27022765
TI  - Two Isostructural Coordination Polymers Showing Diverse Magnetic Behaviors: Weak
      Coupling (Ni(II)) and an Ordered Array of Single-Chain Magnets (Co(II)).
AB  - Two isomorphic 3-D complexes with the formulas [M3(TPTA) (OH)2(H2O)4]n (M = Ni
      for 1 and Co for 2; H4TPTA = [1,1':4',1"-terphenyl]-2',3,3",5'-tetracarboxylic
      acid) have been synthesized and magnetically characterized. Complexes 1 (Ni(II))
      and 2 (Co(II)) have the same 1-D rod-shaped inorganic SBUs but exhibit
      significantly different magnetic properties. Complex 2(Co(II)) is a 3-D
      arrangement of a 1-D Co(II) single-chain magnet (SCM), while complex 1(Ni(II))
      exhibits weak coupling. 

PMID- 27022766
TI  - Experiential learning, leadership, medical students and the army.

PMID- 27022767
TI  - Premenstrual symptom clusters and women's coping style in Korea: happy healthy
      20s application study.
AB  - INTRODUCTION: The purpose of this study was to identify premenstrual symptom
      clusters; and to explore the differences in and effectiveness of coping
      strategies among symptom cluster groups. METHODS: Using the happy healthy 20s
      smartphone application, 349 women with premenstrual symptoms participated in the
      study. Premenstrual symptoms and health outcomes such as perceived health,
      depressive feelings, quality of life, suicidal ideation/attempts and coping
      strategies were explored. Factor analysis and silhouette analysis were used to
      identify premenstrual symptom clusters. Analysis of variance was used to explore
      the differences among symptom clusters in health outcomes and coping strategies.
      RESULTS: Three premenstrual symptom clusters were identified: general discomfort,
      negative affect and turmoil. Three symptom cluster groups experienced different
      health outcomes in perceived health, depressive feelings, quality of life and
      suicidal ideation. However, few differences were noted in participants'
      engagement in coping strategies, frequencies and perceived effectiveness among
      women with different symptom clusters. DISCUSSION: Findings of this study support
      previous reports that women do not receive tailored care for their premenstrual
      symptoms. Learning about the symptom structure, women's ways of coping, and
      perceived effectiveness is important in identifying the issues in current
      premenstrual symptoms management and providing tailored care.

PMID- 27022768
TI  - Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic
      Technology in Rats.
AB  - The kidney normally functions to maintain hemodynamic homeostasis and is a major
      site of damage caused by drug toxicity. Drug-induced nephrotoxicity is estimated
      to contribute to 19- 25% of all clinical cases of acute kidney injury (AKI) in
      critically ill patients. AKI detection has historically relied on metrics such as
      serum creatinine (sCr) or blood urea nitrogen (BUN) which are demonstrably
      inadequate in full assessment of nephrotoxicity in the early phase of renal
      dysfunction. Currently, there is no robust diagnostic method to accurately detect
      hemodynamic alteration in the early phase of AKI while such alterations might
      actually precede the rise in serum biomarker levels. Such early detection can
      help clinicians make an accurate diagnosis and help in in decision making for
      therapeutic strategy. Rats were treated with Cisplatin to induce AKI.
      Nephrotoxicity was assessed for six days using high-frequency sonography, sCr
      measurement and upon histopathology of kidney. Hemodynamic evaluation using 2D
      and Color-Doppler images were used to serially study nephrotoxicity in rats,
      using the sonography. Our data showed successful drug-induced kidney injury in
      adult rats by histological examination. Color-Doppler based sonographic
      assessment of AKI indicated that resistive-index (RI) and pulsatile-index (PI)
      were increased in the treatment group; and peak-systolic velocity (mm/s), end
      diastolic velocity (mm/s) and velocity-time integral (VTI, mm) were decreased in
      renal arteries in the same group. Importantly, these hemodynamic changes
      evaluated by sonography preceded the rise of sCr levels. Sonography-based indices
      such as RI or PI can thus be useful predictive markers of declining renal
      function in rodents. From our sonography-based observations in the kidneys of
      rats that underwent AKI, we showed that these noninvasive hemodynamic
      measurements may consider as an accurate, sensitive and robust method in
      detecting early stage kidney dysfunction. This study also underscores the
      importance of ethical issues associated with animal use in research. 

PMID- 27022769
TI  - Presentation and impact of catheter-associated thrombosis in patients with
      infected long-term central venous catheters: a prospective bicentric
      observational study.
AB  - BACKGROUND: Catheter-associated thrombosis (CAT) in patients with infected long
      term central venous catheter (LTCVC) has been poorly studied. METHODS: We
      prospectively included patients with infected LTCVC and collected clinical data.
      Doppler ultrasound was systematically performed to screen for CAT. Outcome (death
      or infection relapse) was evaluated 12 weeks after infection diagnosis. RESULTS:
      90 patients were included and CAT was diagnosed in 27 (30%). Local signs
      suggesting infection were more frequent in patients with CAT than without (11/27
      versus 8/63, p = 0.03). Outcome was similar in patients with and without CAT.
      However, median duration of antimicrobials was longer (18 versus 14 days, p =
      0.02), catheter removal tended to be more frequent (24/27 versus 46/63, p =
      0.08), and anticoagulant therapy more often prescribed (17/27 versus 6/63, p <
      0.01) in patients with CAT than without. Patients with occlusive thrombosis were
      more likely to have Staphylococcus aureus infections (4/7 versus 1/17, p = 0.02)
      and prolonged positivity of blood-cultures (3/7 versus 1/15, p = 0.02), than
      patients with non-occlusive thrombosis. CONCLUSION: CAT is associated with local
      signs suggesting infection. A more aggressive treatment in CAT cases allowed a
      similar outcome at 12 weeks between patients with and without CAT. Occlusive
      thrombosis represented a subgroup of patients at risk of delayed clearance of
      bacteremia.

PMID- 27022770
TI  - Combat-related Mild Traumatic Brain Injury: Association between Baseline
      Diffusion-Tensor Imaging Findings and Long-term Outcomes.
AB  - Purpose To determine whether functional outcomes of veterans who sustained combat
      related mild traumatic brain injury (TBI) are associated with scalar metrics
      derived from diffusion-tensor (DT) imaging at their initial postdeployment
      evaluation. Materials and Methods This HIPAA-compliant retrospective study was
      approved by the institutional review board, and the requirement to obtain
      informed consent was waived. From 2010 to 2013, initial postdeployment
      evaluation, including clinical assessment and brain magnetic resonance (MR)
      examination with DT imaging, was performed in combat veterans who sustained mild
      TBI while deployed. Outcomes from chart review encompassed initial postdeployment
      clinical assessment as well as later functional status, including evaluation of
      occupational status and health care utilization. Scalar diffusion metrics from
      the initial postdeployment evaluation were compared with outcomes by using
      multivariate analysis. Veterans who did and did not return to work were also
      compared for differences in clinical variables by using t and chi(2) tests.
      Results Postdeployment evaluation was performed a mean of 3.8 years after injury
      (range, 0.5-9 years; standard deviation, 2.5 years). After a mean follow-up of
      1.4 years (range, 0.5-2.5 years; standard deviation, 0.8 year), 34 of 57 veterans
      (60%) had returned to work. Return to work was associated with diffusion metrics
      in multiple regions of white matter, particularly in the left internal capsule
      and the left frontal lobe (P = .02-.05). Overall, veterans had a mean of 46
      health care visits per year during the follow-up period (range, 3-196 visits per
      year; standard deviation, 41 visits per year). Cumulative health care visits over
      time were inversely correlated with diffusion anisotropy of the splenium of the
      corpus callosum and adjacent parietal white matter (P < .05). Clinical measures
      obtained during initial postdeployment evaluation were not predictive of later
      functional status (P = .12-.8). Conclusion Differences in white matter
      microstructure may partially account for the variance in functional outcomes
      among veterans who sustained combat-related mild TBI. ((c)) RSNA, 2016.

PMID- 27022771
TI  - Diet, Nutrition, and Cancer Epigenetics.
AB  - The search for a connection between diet and human cancer has a long history in
      cancer research, as has interest in the mechanisms by which dietary factors might
      increase or decrease cancer risk. The realization that altering diet can alter
      the epigenetic state of genes and that these epigenetic alterations might
      increase or decrease cancer risk is a more modern notion, driven largely by
      studies in animal models. The connections between diet and epigenetic
      alterations, on the one hand, and between epigenetic alterations and cancer, on
      the other, are supported by both observational studies in humans as well as
      animal models. However, the conclusion that diet is linked directly to epigenetic
      alterations and that these epigenetic alterations directly increase or decrease
      the risk of human cancer is much less certain. We suggest that true and
      measurable effects of diet or dietary supplements on epigenotype and cancer risk
      are most likely to be observed in longitudinal studies and at the extremes of the
      intersection of dietary risk factors and human population variability. Careful
      analysis of such outlier populations is most likely to shed light on the
      molecular mechanisms by which suspected environmental risk factors drive the
      process of carcinogenesis.

PMID- 27022772
TI  - Behavioral Nutrition Interventions Using e- and m-Health Communication
      Technologies: A Narrative Review.
AB  - e- and m-Health communication technologies are now common approaches to improving
      population health. The efficacy of behavioral nutrition interventions using e
      health technologies to decrease fat intake and increase fruit and vegetable
      intake was demonstrated in studies conducted from 2005 to 2009, with
      approximately 75% of trials showing positive effects. By 2010, an increasing
      number of behavioral nutrition interventions were focusing on body weight. The
      early emphasis on interventions that were highly computer tailored shifted to
      personalized electronic interventions that included weight and behavioral self
      monitoring as key features. More diverse target audiences began to participate,
      and mobile components were added to interventions. Little progress has been made
      on using objective measures rather than self-reported measures of dietary
      behavior. A challenge for nutritionists is to link with the private sector in the
      design, use, and evaluation of the many electronic devices that are now available
      in the marketplace for nutrition monitoring and behavioral change.

PMID- 27022773
TI  - Authors' Response to Abourbih and Baldwin.

PMID- 27022775
TI  - Neonatology and Laboratory Medicine Green Anne et al Neonatology and Laboratory
      Medicine 322pp ACB Venture Publications 9780902429413 0902429418.
AB  - This is one of the most concise, up to date and informative texts on neonatal and
      laboratory medicine. It is written as a basic handbook with a wide audience in
      mind, including junior doctors, laboratory scientists and neonatal nurses. It is
      also relevant to practitioners who work in paediatric medicine and nursing. The
      range of material is comprehensive and the way in which the chapters lead the
      reader is authoritative and informative. The authors present the information in a
      clear and concise way, and the text is augmented by flow diagrams. This is an
      excellent resource and an essential reference in neonatal or paediatric intensive
      care units. It will also be a valuable resource for those undertaking post
      qualifying awards in neonatal or paediatric nursing.

PMID- 27022774
TI  - Attitudes of Chinese Oncology Physicians Toward Death with Dignity.
AB  - BACKGROUND: Death with dignity (DWD) refers to the refusal of life-prolonging
      measures for terminally ill patients by "living wills" forms in advance. More and
      more oncology physicians are receiving DWD requests from advance cancer patients
      in mainland China. OBJECTIVE: The study objective was to investigate the
      attitudes of Chinese oncology physicians toward the legalization and
      implementation of DWD. METHODS: A questionnaire investigating the understanding
      and attitudes toward DWD was administered to 257 oncology physicians from 11
      hospitals in mainland China. RESULTS: The effective response rate was 86.8%
      (223/257). The majority of oncology physicians (69.1%) had received DWD requests
      from patients. Half of the participants (52.5%) thought that the most important
      reason was the patients' unwillingness to maintain survival through machines. One
      third of participants (33.0%) attributed the most important reason to suffering
      from painful symptoms. Most oncology physicians (78.9%) had knowledge about DWD.
      A fifth of respondents did not know the difference between DWD and euthanasia,
      and a few even considered DWD as euthanasia. The majority of oncology physicians
      supported the legalization (88.3%) and implementation (83.9%) of DWD.
      CONCLUSIONS: Many Chinese oncology physicians have received advanced cancer
      patients' DWD requests and think that DWD should be legalized and implemented.
      Chinese health management departments should consider the demands of physicians
      and patients. It is important to inform physicians about the difference between
      DWD and euthanasia, as one-fifth of them were confused about it.

PMID- 27022776
TI  - Complexity and healthcare : an introduction Sweeney Kieran Griffiths Frances
      Complexity and healthcare : an introduction 183pp Radcliffe Medical Press
      9781857755596 1857755596.
AB  - This book sets out to offer insights into how the scientific approach to health
      care contains a number of paradoxes. It goes on to demonstrate how these can be
      addressed by the development of a more robust model that takes into account the
      unpredictability and uncertainty of the healthcare world.

PMID- 27022777
TI  - Post-ABVD/pre-radiotherapy (18)F-FDG-PET provides additional prognostic
      information for early-stage Hodgkin lymphoma: a retrospective analysis on 165
      patients.
AB  - OBJECTIVE: To evaluate the prognostic role of both interim fluorine-18
      fludeoxyglucose positron emission tomography (i-(18)F-FDG-PET) and end-of
      chemotherapy fluorine-18 fludeoxyglucose positron emission tomography (eoc-(18)F
      FDG-PET) in patients with early-stage Hodgkin lymphoma (HL). METHODS: We screened
      257 patients with early-stage HL treated with combined modality therapy between
      March 2003 and July 2011. All were staged using fluorine-18 fludeoxyglucose
      positron emission tomography ((18)F-FDG-PET) before chemotherapy and after two
      doxorubicin, bleomycin, vinblastine and dacarbazine cycles (i-(18)F-FDG-PET); 165
      patients were also evaluated by (18)F-FDG-PET at the end of chemotherapy (eoc
      (18)F-FDG-PET). RESULTS: After revision, 85% of patients were negative for i
      (18)F-FDG-PET and 15% were positive. After eoc-(18)F-FDG-PET revision, 23
      patients had a positive scan. The median follow-up was 56 months. The 5-year
      overall survival (OS) and progression-free survival (PFS) for the whole cohort
      were 97.5% and 95.6%, respectively. For i-(18)F-FDG-PET-negative and i-(18)F-FDG
      PET-positive patients, the 5-year PFS rates were 98% and 84%, respectively; for
      eoc-(18)F-FDG-PET-negative and eoc-(18)F-FDG-PET-positive patients, the 5-year
      PFS rates were 97% and 78%, respectively. Combining the i-(18)F-FDG-PET and eoc
      (18)F-FDG-PET results, the 5-year PFS were 97%, 100% and 82% in
      negative/negative, positive/negative and positive/positive groups, respectively.
      The 5-year OS rates were 98% and 83% in eoc-(18)F-FDG-PET-negative and eoc-(18)F
      FDG-PET-positive patients, respectively; the 5-year OS was 98%, 100% and 83% in
      negative/negative, positive/negative and positive/positive groups, respectively.
      CONCLUSION: This study provides additional information on the prognostic role of
      i-(18)F-FDG-PET and eoc-(18)F-FDG-PET in early-stage HL. As data are accumulating
      and the clinical scenario is rapidly evolving, we might need to rethink the use
      of (18)F-FDG-PET as a prognostic marker for early-stage HL in the near future.
      ADVANCES IN KNOWLEDGE: This study provides additional information on the
      prognostic role of i-(18)F-FDG-PET and eoc-(18)F-FDG-PET in early-stage HL. On
      the basis of the present data, we may suggest to use eoc-(18)F-FDG-PET as a
      strong prognostic marker, especially for patients with i-(18)F-FDG-PET
      positivity.

PMID- 27022778
TI  - Screening of biologically active monosaccharides: growth inhibitory effects of d
      allose, d-talose, and l-idose against the nematode Caenorhabditis elegans.
AB  - We compared the growth inhibitory effects of all aldohexose stereoisomers against
      the model animal Caenorhabditis elegans. Among the tested compounds, the rare
      sugars d-allose (d-All), d-talose (d-Tal), and l-idose (l-Ido) showed
      considerable growth inhibition under both monoxenic and axenic culture
      conditions. 6-Deoxy-d-All had no effect on growth, which suggests that C6
      phosphorylation by hexokinase is essential for inhibition by d-All. 

PMID- 27022779
TI  - Perinatal outcomes after adopting 1- versus 2-step approach to diagnosing
      gestational diabetes.
AB  - OBJECTIVE: The American College of Obstetricians and Gynecologists (ACOG) and the
      IADPSG (International Association of Diabetes and Pregnancy Study Groups)
      proposed distinct approaches to diagnosing gestational diabetes mellitus (GDM).
      We sought to analyze these paradigms: (1) ACOG 2-step approach where screening is
      followed by diagnostic testing, (2) IADPSG 1-step diagnostic testing. STUDY
      DESIGN: We reviewed data from pregnant women (24-28 wks) screened for GDM over
      two periods: (1) November 2011-May 2012 (2) November 2012-May 2013. Period 1: 2
      step approach (screening 1-h glucose challenge test (GCT) followed by a
      diagnostic 3-h 100-g glucose tolerance test (GTT) when abnormal (>=140 mg/dl)).
      Period 2: an abnormal value after a 2-h 75-g GTT result was diagnostic of GDM. We
      compared the incidence of GDM and perinatal outcomes using either approach.
      RESULTS: Out of 471 patients screened by ACOG 2-step approach, 72 (15.3%) had an
      abnormal 1-h screening and underwent the 3-h diagnostic GTT, and 26 (5.5%)
      developed GDM. The 1-step approach resulted in 53 (15.96%) with GDM of a total
      332 evaluated. There was no statistically significant difference in perinatal
      outcomes between the two cohorts. Maternal weight at the start and the end of
      pregnancy was greater for patients diagnosed by the ACOG 2-step approach.
      CONCLUSION: Adopting 1-step approach (ADA) to diagnose GDM resulted in a 3-fold
      increase in prevalence of GDM with no differences in perinatal outcomes.

PMID- 27022780
TI  - Finite-size scaling of the magnetization probability density for the critical
      Ising model in slab geometry.
AB  - The magnetization probability density in d  =  2 and 3 dimensional Ising models
      in slab geometry of volume [Formula: see text] is computed through Monte-Carlo
      simulation at the critical temperature and zero magnetic field. The finite-size
      scaling of this distribution and its dependence on the system aspect-ratio
      [Formula: see text]and boundary conditions are discussed. In the limiting case
      [Formula: see text] of a macroscopically large slab ([Formula: see text]) the
      distribution is found to scale as a Gaussian function for all tested system sizes
      and boundary conditions.

PMID- 27022781
TI  - Preparation of Carbon Nanosheets at Room Temperature.
AB  - Amphiphilic molecules equipped with a reactive, carbon-rich "oligoyne" segment
      consisting of conjugated carbon-carbon triple bonds self-assemble into defined
      aggregates in aqueous media and at the air-water interface. In the aggregated
      state, the oligoynes can then be carbonized under mild conditions while
      preserving the morphology and the embedded chemical functionalization. This novel
      approach provides direct access to functionalized carbon nanomaterials. In this
      article, we present a synthetic approach that allows us to prepare hexayne
      carboxylate amphiphiles as carbon-rich siblings of typical fatty acid esters
      through a series of repeated bromination and Negishi-type cross-coupling
      reactions. The obtained compounds are designed to self-assemble into monolayers
      at the air-water interface, and we show how this can be achieved in a Langmuir
      trough. Thus, compression of the molecules at the air-water interface triggers
      the film formation and leads to a densely packed layer of the molecules. The
      complete carbonization of the films at the air-water interface is then
      accomplished by cross-linking of the hexayne layer at room temperature, using UV
      irradiation as a mild external stimulus. The changes in the layer during this
      process can be monitored with the help of infrared reflection-absorption
      spectroscopy and Brewster angle microscopy. Moreover, a transfer of the
      carbonized films onto solid substrates by the Langmuir-Blodgett technique has
      enabled us to prove that they were carbon nanosheets with lateral dimensions on
      the order of centimeters. 

PMID- 27022782
TI  - Antenatal Corticosteroid Administration for Reducing the Risk of Neonatal
      Morbidities from Prematurity.

PMID- 27022783
TI  - Comparison of Two- and Three-dimensional Ultrasonography in the Evaluation of
      Lesion Level in Fetuses with Spina Bifida.
AB  - PURPOSE: To evaluate the precision of both two- and three-dimensional
      ultrasonography in determining vertebral lesion level (the first open vertebra)
      in patients with spina bifida. METHODS: This was a prospective longitudinal study
      comprising of fetuses with open spina bifida who were treated in the fetal
      medicine division of the department of obstetrics of Hospital das Clinicas of the
      Universidade de Sao Paulo between 2004 and 2013. Vertebral lesion level was
      established by using both two- and three-dimensional ultrasonography in 50
      fetuses (two examiners in each method). The lesion level in the neonatal period
      was established by radiological assessment of the spine. All pregnancies were
      followed in our hospital prenatally, and delivery was scheduled to allow
      immediate postnatal surgical correction. RESULTS: Two-dimensional sonography
      precisely estimated the spina bifida level in 53% of the cases. The estimate
      error was within one vertebra in 80% of the cases, in up to two vertebrae in 89%,
      and in up to three vertebrae in 100%, showing a good interobserver agreement.
      Three-dimensional ultrasonography precisely estimated the lesion level in 50% of
      the cases. The estimate error was within one vertebra in 82% of the cases, in up
      to two vertebrae in 90%, and in up to three vertebrae in 100%, also showing good
      interobserver agreement. Whenever an estimate error was observed, both two- and
      three-dimensional ultrasonography scans tended to underestimate the true lesion
      level (55.3% and 62% of the cases, respectively). CONCLUSIONS: No relevant
      difference in diagnostic performance was observed between the two- and three
      dimensional ultrasonography. The use of three-dimensional ultrasonography showed
      no additional benefit in diagnosing the lesion level in the fetuses with spina
      bifida. Errors in both methods showed a tendency to underestimate lesion level.

PMID- 27022784
TI  - Use of Medicinal Plants with Teratogenic and Abortive Effects by Pregnant Women
      in a City in Northeastern Brazil.
AB  - PURPOSE: The purpose of this study is to verify the use of medicinal plants by
      pregnant women treated at four Basic Health Units and at a public maternity
      facility in Brazil's northeast. METHODS: This is a cross-sectional, quantitative
      study, performed between February and April 2014. The subjects were 178 pregnant
      women, aged 18 to 42 years. To collect data, a structured questionnaire with
      dichotomous and multiple choice questions was used. To verify the correlation
      between the variables, Pearson's chi-square test was used. RESULTS: The study
      showed that 30.9% of the pregnant women used medicinal plants, and boldo was the
      most cited (35.4%). All the plants utilized, except lemongrass, have toxic
      effects in pregnancy, according to Resolution SES/RJ N degrees  1757. There was
      no statistically significant correlation between social class and use of
      medicinal plants. CONCLUSION: The health of the study participants and their
      unborn children is at risk due to the inappropriate use of medicinal plants.

PMID- 27022785
TI  - Continued Compliance and Degree of Satisfaction in Nulligravida and Parous Women
      with Intrauterine Contraceptive Devices.
AB  - PURPOSE: To evaluate the compliance and degree of satisfaction of nulligravida
      (has not given birth) and parous (had already given birth) women who are using
      intrauterine devices (IUDs). METHODS: A cross-sectional cohort study was
      conducted comparing nulligravida and parous women who had had an IUD inserted
      between July 2009 and November 2011. A total of 84 nulligravida women and 73
      parous women were included. Interviews were conducted with women who agreed to
      participate through telephone contact. Statistical analysis was performed with
      Student's t-test and Mann-Whitney test for numeric variables; Pearson's chi
      square test to test associations; and, whenever pertinent, Fisher's exact test
      for categorical variables. A survival curve was constructed to estimate the
      likelihood of each woman continuing the use of the IUD. A significance level of
      5% was established. RESULTS: When compared with parous women, nulligravida women
      had a higher education level (median: 12 vs. 10 years). No statistically
      significant differences were found between the nulligravida and parous women with
      respect to information on the use of the IUD, prior use of other contraceptive
      methods, the reason for having chosen the IUD as the current contraceptive
      method, reasons for discontinuing the use and adverse effects, compliance, and
      degree of satisfaction. The two groups did not show any difference in terms of
      continued use of the IUD (p = 0.4). CONCLUSION: There was no difference in
      compliance or the degree of satisfaction or continued use of IUDs between
      nulligravida and parous women, suggesting that IUD use may be recommended for
      women who have never been pregnant.

PMID- 27022786
TI  - Predictive Capability of HPV and Pap Tests in Screening for Cervical Cancer over
      a Three-Year Follow-up.
AB  - PURPOSE: To compare the predictive capability of HPV and Pap smear tests for
      screening pre-cancerous lesions of the cervix over a three-year follow-up, in a
      population of users of the Brazilian National Health System (SUS). METHODS: This
      is a retrospective cohort study of 2,032 women with satisfactory results for Pap
      smear and HPV tests using second-generation hybrid capture, made in a previous
      study. We followed them for 36 months with data obtained from medical records,
      the Cervix Cancer Information System (SISCOLO), and the Mortality Information
      System (SIM). The outcome was a histological diagnosis of cervical
      intraepithelial neoplasia grade 2 or more advanced lesions (CIN2+). We
      constructed progression curves of the baseline test results for the period, using
      the Kaplan-Meier method, and estimated sensitivity, specificity, positive and
      negative predictive value, and positive and negative likelihood ratios for each
      test. RESULTS: A total of 1,440 women had at least one test during follow-up.
      Progression curves of the baseline test results indicated differences in
      capability to detect CIN2+ (p < 0.001) with significantly greater capability when
      both tests were abnormal, followed by only a positive HPV test. The HPV test was
      more sensitive than the Pap smear (88.7% and 73.6%, respectively; p < 0.05) and
      had a better negative likelihood ratio (0.13 and 0.30, respectively). Specificity
      and positive likelihood ratio of the tests were similar. CONCLUSIONS: These
      findings corroborate the importance of HPV test as a primary cervical cancer
      screening.

PMID- 27022787
TI  - High Risk HPV E6/E7 Oncoprotein Expression in Women with High Grade Squamous
      Intraepithelial Lesion.
AB  - PURPOSE: To correlate the expression of high-risk HPV E6 mRNA with pap smear,
      colposcopy, and biopsy results in women with high grade squamous intraepithelial
      lesion (HSIL). METHODS: A cross-sectional study was performed on women referred
      for primary care services after cytological diagnosis of HSIL. We evaluated the
      expression of E6/E7 mRNA of HPV types 16,18,31,33, and 45 and correlated the
      results with those of Pap smear, colposcopy, and biopsy. For
      amplification/detection of mRNA E6 / E7 we used NucliSENSEasyQ kit to detect HPV
      mRNA by polymerase chain reaction with primers/probes for HPV types 16, 18, 31,
      33, and 45. RESULTS: Out of 128 valid tests, the results of 30 (23.4%) tests were
      negative and 98 (70%) tests were positive. Only one type of HPV was detected in
      87.7% of the E6/E7 mRNA positive cases. HPV16 was detected in 61.2% of the cases,
      followed by HPV33 (26.5%), HPV31 (17.3%), HPV18 (10%), and HPV45 (4.08%). Pap
      smear tests revealed that the E6/E7 test was positive in 107 (83.8%) women with
      atypical squamous cells - high grade (ASC-H), HSIL, or higher. The E6/E7 test was
      positive in 69 (57.5%) specimens presenting negative cytology results. When
      analyzing the association with colposcopy results, the frequency of positive
      E6/E7 results increased with the severity of the injury, ranging from 57.1% in
      women without colposcopy-detected injury to 86.5% in those with higher levels of
      colposcopy findings. Of the 111 women who underwent biopsy and E6/E7 testing, the
      E6/E7 test was positive in 84.7% of the women who presented with lesions of
      cervical intraepithelial neoplasia (CIN) grade 2 or higher. Finally, 41.2% of
      women with a negative biopsy presented a positive E6/E7 test. CONCLUSIONS: E6/E7
      mRNA expression was higher in women with HSIL and CIN grade 2 or higher.

PMID- 27022788
TI  - Pseudoachalasia: A review.
AB  - Pseudoachalasia presents typically like achalasia. It account for only 2.4-4% of
      patients presenting with achalasia-like symptoms. Clinical, radiologic and
      endoscopic findings resemble those of achalasia but treatment and prognosis are
      different in these conditions. The aim of this review is to give an overview of
      the condition and highlight challenges in diagnosis and distinguishing features
      between the two conditions. A review of the publications obtained from Medline
      search, medical libraries, and Google on 'pseudoachalasia' and 'secondary
      achalasia' was done. A total of 50 articles were retrieved and used for this
      review. There has been tremendous efforts towards establishing the diagnosis of
      pseudoachalasia both clinically and with the use of modern investigative
      modalities but to date its still difficult to distinguish it from achalasia.
      Endoscopy, endoscopic ultrasonography and computerized tomography scan have shown
      promising results. 

PMID- 27022789
TI  - Surgical inpatient mortality in a Nigerian Tertiary Hospital.
AB  - BACKGROUND: There is paucity of literatures on audit of mortality in the surgical
      units of tertiary hospitals in the country. This has made the spectrum of
      mortality not to been known in some of the centers and therefore, there is a
      great disparity and dearth in apportioning health care services appropriately.
      AIM: The determination of the pattern of mortality in a surgical unit helps in
      planning, provision of quality surgical care and prioritizing of limited
      resources in developing countries. METHODS: This is a retrospective study of all
      patients who died during admission into surgical wards of our hospital between
      2007 and 2012. Data on demography and events leading to death were collected and
      analyzed from all surgical wards, the emergency unit, surgical outpatients, and
      theater records. RESULTS: A total of 527 deaths occurred among the 8230 patients
      admitted during the 6-year period giving a mortality rate of 6.4%. Three hundred
      and forty-five (65.5%) were male, while 282 (34.5%) were females. The mortality
      rates in units were as follows: Burn and plastic (23.1%), general surgery (5.5%),
      neurosurgery (7.9%), urology (6.0%), orthopedics (3.8%), pediatric surgery
      (3.4%), and cardiothoracic surgery (11.9%). The yearly mortality rate were as
      follows, respectively: 2007 (7.1%), 2008 (6.0%), 2009 (4.5%), 2010 (6.5%), 2011
      (7.2%), and 2012 (7.5%). About 84.6% of the patients died within 1 month on
      admission. The leading causes of mortality were trauma (41.8%) and cancer
      (32.4%). Most of the deaths (64.9%) occurred between 20- and 70-year-old.
      CONCLUSION: Trauma and cancer constitute a great deal of health burden in our
      region. Strong legislation and screenings with timely interventions are required.

PMID- 27022790
TI  - Prevalence and risk factors for Staphylococcus aureus and methicillin-resistant
      Staphylococcus aureus nasal carriage inpatients in a tertiary care hospital's
      chest clinic in Turkey.
AB  - AIM: We aimed to determine the prevalence and associated risk factors for nasal
      methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA/MRSA)
      carriage among patients admitted to a chest clinic of a tertiary care hospital in
      this study. MATERIALS AND METHODS: Nasal samples were taken from anterior nares
      were cultured in CHROMagar S. aureus plates, MRSA was determined by disc
      diffusion method (cefoxitin 30 MUg) according to the Clinical and Laboratory
      Standards Institute guidelines and CHROMagar MRSA plates. A questionnaire was
      applied to determine the demographic characteristics of the participants and risk
      factors for carriage. Fisher's exact test, univariate and multivariate logistic
      regression analysis were used. A P < 0.05 indicated a statistically significant
      difference. RESULTS: This is a cross-sectional study covering all the patients (n
      = 431) admitted to Kayseri Training and Research Hospital's Chest Clinic from
      January 1st to 31st 2014. Of all these patients 55 (12.8%) were nasal S. aureus
      carriers. MRSA positivity was in five among these patients. In multivariate
      analysis, being under 65 years of age (odds ratio [OR], 1.9; 95% confidence
      interval [CI], 1.0-3.3), and having prosthesis (OR, 4.8; 95% CI, 1.6-13.9) were
      found as risk factors for MSSA colonization. CONCLUSION: The prevalence of nasal
      carriage of MSSA was low in our study population. The only risk factors playing
      role in carriage were found as being under the age of 65 and having prosthesis.

PMID- 27022791
TI  - The evaluation of the angles of Eustachian tubes in the patients with chronic
      otitis media on the temporal computerized tomography.
AB  - INTRODUCTION: Chronic otitis media (COM), affecting all over the world and in a
      wide range of age groups in Turkey, is an important cause of ear discharge and
      hearing loss. The main clinical manifestations are tympanic membrane perforation,
      ear, nose and throat problems. On the tympanic membrane perforation becomes
      persistent and cholesteatoma development, there are a lot of opinions today.
      Especially in the pathology associated with otitis media with effusion eustachian
      tube, it is known that COM and cholesteatoma develop. MATERIALS AND METHODS: In
      our study, we interpreted 210 patients' temporal computed tomography (CT).
      Seventy of these 210 patients had otitis media with cholesteatoma, 70 patients
      had only otitis media without cholesteatoma, and 70 patients had no otitis media.
      The eustachian tubes were evaluated using temporal CT multiplanar reconstruction
      method. Angles with the horizontal plane of the eustachian tube and Reid and
      tubotympanic angles were measured. RESULTS: The angles between eustachian tube
      and horizontally oriented Reid plane of the patients with cholesteatoma were
      found to be significantly lower than the patients with otitis media without
      cholesteatoma and the patients with no history of otitis media. For the
      tubotympanic angle, no statistically significant differences were observed
      between the groups. CONCLUSION: These results suggest that the decrease in the
      angle with the horizontal plane of Reid in the eustachian tube in adults may play
      a significant role in the etiology of cholesteatoma.

PMID- 27022792
TI  - Relevance of a laboratory physician's report to patient care in a tertiary health
      center.
AB  - INTRODUCTION: Investigation results traditionally are given in two parts:
      Investigation results and report. When both are provided for a test done, reports
      offer in depth information, explanation and clarification of results. This trend
      has been lost over time as results are the only documentation routinely given
      currently in conventional hospital practice except reports are specially
      requested for although the service is obtainable at no extra cost to the patient
      or attending physician. AIM: To access the necessity of laboratory report as part
      of investigation results and reasons for non utilization of laboratory report
      services by physicians. METHOD: A descriptive cross-sectional study was conducted
      amongst doctors of varying cadres in 3 specialties (Physician, Surgeon, Gender
      practitioners) at the University of Benin Teaching Hospital, Benin City, Nigeria.
      Data was collected from 121 participating doctors using a structured 19 item self
      administered questionnaire. The data was analyzed using IBM-SPSS Version 20.0.
      RESULTS: Most respondents agreed that the investigation results currently
      obtained from the laboratory were useful but would be better if laboratory
      reports accompanied them. Over 70% of the doctors noted that the above sometimes
      held true only sometimes and not always as stated by 28.1% of doctors. More than
      90% of the doctors have knowledge of the difference between laboratory results
      and report; the necessity of a lab physician's report for every investigation
      requested for and its potential benefits such an investigation reporting system
      will have on patient management. Although most doctors (81.8%) discuss laboratory
      results with lab physicians, they do not routinely consult them to achieve the
      improved value of investigation results until a critical period of necessity
      arises. CONCLUSION: Laboratory investigations would offer doctors more
      information, which translates to enhanced patient care if investigation results
      are mandatorily accompanied by a laboratory report.

PMID- 27022793
TI  - Knowledge and perception of plastic surgery among tertiary education students in
      Enugu, South-East Nigeria.
AB  - BACKGROUND: Knowledge, perception, and acceptance of plastic surgery among any
      population are influenced by channel of presentation. A good understanding of the
      public awareness will define the way plastic surgery services will be provided.
      AIM: To assess the knowledge, awareness of availability, and acceptance of
      plastic surgery practice in Enugu, South East Nigeria. MATERIALS AND METHODS: A
      questionnaire-based prospective study. RESULTS: The electronic media is the most
      common medium of awareness. Less than half the sample knew about the existence of
      plastic surgeons in Enugu even though a large proportion was aware of the
      existence of plastic surgery as a specialty. The concentration of plastic
      surgeons in a center is directly related to awareness of plastic surgery services
      in that facility. The most common esthetic procedure done by a plastic surgeon in
      Enugu is tattoo removal and scar refashioning. Orthopedic surgeons are thought to
      be key players in the management of burn patients as much as the plastic surgeons
      due to the "SIGNPOST EFFECT." CONCLUSION: The level of awareness is high in the
      sampled population with associated increase in acceptance of its practice and
      willing utilization. All public hospitals should be encouraged to employ the
      services of plastic surgeons. Appropriate branding of specialized hospitals where
      plastic surgery service is available will advance the practice significantly.

PMID- 27022794
TI  - Pattern and location of intracerebral hemorrhage in Enugu, South-East Nigeria: A
      review of 139 cases.
AB  - INTRODUCTION: The incidence rates and location of nontraumatic intracerebral
      hemorrhage (ICH) have been shown to vary between population and races. Knowledge
      of ICH patterns may give some insight into the etiology of ICH and help reduce
      its burden particularly among Africans where health infrastructure is poorly
      developed. We present a retrospective review of ICH using a modern neuroimaging
      technique. OBJECTIVES: To determine the pattern and location of ICH among
      patients presenting in a tertiary hospital in Enugu. METHODS: All the medical and
      computer tomography records of patients with a clinical diagnosis of hemorrhagic
      stroke with the location of hemorrhage clearly specified and complete patients'
      data were reviewed. The study duration was 11 years (January 2003 to December
      2013). Relevant data were obtained, and statistical analysis was done using SPSS
      version 19 (IBM Corporation, New York, USA). RESULTS: A total of 139 (17.4%) out
      of 799 scans done over the period under review were analyzed. The frequency of
      lobar and deep cerebral hemorrhages (LH and DCHs) was 46.8% and 53.2%,
      respectively. The most common types of hemorrhage in men and women were deep
      cerebral (52.2% and 55.3%, respectively). Five percent (7/139) of all hemorrhages
      occurred in the cerebellum. Age distribution of the location of ICH shows that
      LHs peaked at 16-39 years while DCHs peaked at 40-49 years. There was not
      statistically significant difference between mean ages of occurrence of LH and
      hemorrhages of other locations. CONCLUSION: Frequency of LH and DCH varied with
      age as LH peaked before the age of 40 while deep cerebral at 40-49 years. The age
      distribution of different types of ICH may suggest a higher role of other factors
      apart from hypertension. Further studies are required to establish the risk
      factors of LH and DCHs in our environment.

PMID- 27022796
TI  - Duplex ultrasound: Indications and findings in a newly created facility at the
      University of Calabar Teaching Hospital, Calabar.
AB  - BACKGROUND: Peripheral limb vascular diseases form one of the most common
      diseases that affect the middle-aged and the elderly. Duplex ultrasound has
      revolutionized medicare and is an important modality for investigating them.
      Unfortunately, this modality is still not popular in our environment and in
      Calabar was used for the 1st time 4 years ago. This work is, therefore, to report
      our findings and hopefully increase the awareness of its benefits thereby
      improving and hastening the diagnosis of vascular pathologies in our environment.
      METHODS: A prospective study that took place in the University of Calabar
      Teaching Hospital, Calabar between March 2011 and August 2014. The study included
      patients with pain, swelling, ulceration, as well as outright gangrene of the
      upper or lower limbs. Others were stroke or transient ischemic attack (TIA)
      patients, and patients with renal grafts. The scans were carried out in Radiology
      Department using a digital color Doppler ultrasound. RESULTS: Seventy-six
      patients were scanned during this period. They were more males (67%) than females
      (33%). The indications were mainly leg swelling and pain 25 (33%), stroke/TIA 10
      (13%), and deep venous thrombosis (DVT) 10 (13%) The most common scan done was
      peripheral limb Doppler, 49 (64.5%).The majority of the scans showed no
      abnormality followed by chronic venous insufficiency 13 (17.1%) and lower limb
      arteriosclerosis 7 (9.2%) which was noted to be common among diabetics and
      hypertensive. DVT was another common finding and 4 out of 10 patients in whom DVT
      was suspected clinically showed sonographic evidence of the condition.
      CONCLUSION: Duplex ultrasound has been shown to diagnose varied vascular
      pathologies even in a locale where it is a relatively new technique. It is
      recommended that timely referrals be made, and mobile Doppler units be acquired
      to save more lives and limbs in the developing world.

PMID- 27022795
TI  - Fibroadenoma: Accuracy of clinical diagnosis in females aged 25 years or less.
AB  - BACKGROUND: Accurate clinical diagnosis of fibroadenoma in young females is
      desirable because of the possibility of nonoperative treatment for those desiring
      it. OBJECTIVES: To determine the accuracy of the clinical diagnosis of
      fibroadenoma in patients aged <= 25 years. PATIENTS AND METHODS: A prospective
      study of all patients with breast disease presenting to the breast clinic was
      conducted from January 2004 to December 2008. RESULTS: During the study period,
      145 patients aged <=25 years presented with breast lumps. In this group, a
      clinical diagnosis of fibroadenoma was made in 100 (69.0%), fibrocystic disease
      in 32 (22.1%), breast cancer in 4 (0.03%) patients, the remaining were benign
      lesions. Excision biopsy was done for 81 (55.9%) patients. Of these 81 patients,
      only 62 (76.5%) returned with histology report. The histological diagnosis was
      fibroadenoma in 45 (72.5%) patients with a mean age of 21.4 years. Their ages
      range from 18 to 25 years. The histological diagnosis was fibrocystic disease in
      9 (14.5%) and malignant phyllodes in 1 (1.6%) patient. The remaining 7 (11.3%)
      patients had other types of benign lesions. For fibroadenoma, true positive cases
      were 42, false positive 7 and false negative 3, and true negative 10. Therefore,
      the sensitivity of clinical diagnosis of fibroadenoma was 93.3%, while
      specificity was 58.8%. CONCLUSION: The sensitivity of clinical diagnosis of
      fibroadenoma in patients aged <=25 years was good, though specificity is low.

PMID- 27022797
TI  - Carotid intima-media thickness and insulin resistance changes in patients who
      underwent sleeve gastrectomy: A prospective study.
AB  - OBJECTIVES: Our aim was to examine changes in insulin resistance, Carotid Intima
      Media Thickness (CIMT), in morbid obese patients without any known associated
      chronic diseases who underwent sleeve gastrectomy. MATERIALS AND METHODS: The
      subjects of this study were patients with minimum BMI of 40, who did not have any
      known chronic diseases. Sleeve gastrectomy was performed and perioperative
      control endoscopy was performed. The following values were measured before the
      operation and after follow-up period after the operation: Fasting blood glucose
      and insulin, lipid profile, BMI, liver function tests, right and left CIMT.
      Furthermore, the patients' insulin resistance was calculated by HOMA method, and
      the values of 2.7. PARTICIPANTS: Six-teen patients (14 women and 2 men, average
      age: 39.12 +/- 10.63 years), who did not have a known additional chronic disease,
      took part in the study. RESULTS: There was a significant difference between
      baseline and follow-up values of the patients, and the mean weight loss was
      20.5%. Given the statistical evaluation of baseline and follow-up values, there
      was a significant difference in BMI, insulin resistance rates and right and left
      CIMT values. CONCLUSIONS: Bariatric surgery may provide some additional
      advantages for the management of cardiovascular risks in obese patients. However,
      it should be kept in mind that the most important components of fight against
      obesity are appropriate diet and exercise programs.

PMID- 27022798
TI  - Routine hemoglobin electrophoresis for pediatric surgery day case in at-risk
      populations: Suggested algorithm for screening using clinical risk factors.
AB  - BACKGROUND: Hemoglobin electrophoresis (HBE) is a part of the preoperative
      routine requested by anesthetists. However, the prevalence of hemoglobinopathy in
      the population is low. This study aims to determine the clinical risk factors for
      hemoglobinopathies and propose clinical guidelines for preoperative screening of
      patients for pediatric day care surgery. PATIENTS AND METHODS: A prospective
      study carried out over 12 months. Consecutive patients aged 6 months and older
      who had day case surgery were recruited to the study. Biodata and relevant
      clinical data were collated and documented in a proforma and analyzed using a
      statistical package for social sciences version 17. RESULTS: There were 124
      patients106 boys and 18 girls. The median age was 3 years. Scrotal lesions were
      the most common conditions managed (71.7%). Seventy-eight percent of patients had
      HbAA, 15.3% had HbAS, and 4.8% had HbAC while 0.8% each had both HbSC and HbSS.
      At least one parent of 78.2% knew their Hb phenotype, of which, 79% were HbAA. A
      history of jaundice (P = 0.0001), hand and foot syndrome (P = 0.0001), frontal
      bossing (P = 0.0001), and low packed cell volume at surgery (P = 0.001) were
      found significant in predicting hemoglobinopathies. There was no mortality.
      CONCLUSION: Risk factors for hemoglobinopathies from this study included a
      positive history of jaundice, hand and foot syndrome, frontal bossing, and
      anemia. Proposed guidelines for HBE screening include the presence of
      hemoglobinopathy in one parent if one parent has sickle cell trait, and the other
      parent's genotype is unknown or if any of the risk factors is present.

PMID- 27022799
TI  - Evaluation of two different respiratory physiotherapy methods after thoracoscopy
      with regard to arterial blood gas, respiratory function test, number of days
      until discharge, cost analysis, comfort and pain control.
AB  - INTRODUCTION: Although the methods used in thoracic surgery have been developing
      rapidly over the last five decades, postoperative pulmonary complications are
      seen in this field more than in other surgical branches. We aimed at comparing
      the acute effects of incentive spirometry (IS) and breathing retraining exercises
      by a respiratory physiotherapist or experienced physiotherapist. METHODS:
      Patients were randomized into two groups as spirometry and physiotherapist.
      Combined respiratory exercises were implemented through IS inspirometry group and
      by a physiotherapist in physiotherapist group. Blood gas, respiratory function
      tests, survey results of the Burford pain thermometer, discharge days, and cost
      analyses of both groups were examined just before the beginning of physiotherapy
      and on the 3rd day of therapy. RESULTS: There were no statistical difference in
      first and last values of pH and PCO2and also there were no difference between
      groups (P > 0.05). Forced expiratory volume one second (FEV1) values are
      statistically increased compared to basal levels in both groups and mean
      difference in FEV1values was statistically increased in physiotherapist group
      compared to spirometry group (P < 0.001). Forced vital capacity (FVC), PO2and
      SaO2 values are statistically increased compared to basal levels in both groups
      but mean difference in FVC values was not statistically different between groups
      (P > 0.05). Cost analysis was not statistically different, mean hospitalization
      day and mean pain score were statistically decreased in physiotherapist group.
      CONCLUSIONS: Based on the outcome of this study, respiratory physiotherapy
      methods carried out by a respiratory physiotherapist are more effective in acute
      cardiothoracic conditions after thoracotomy compared to IS by patients.

PMID- 27022800
TI  - Rhinoscintigraphic analysis of nasal mucociliary function in patients with Bell's
      palsy.
AB  - OBJECTIVE: Mucociliary transport (MCT) is an important defense mechanism of the
      respiratory tract. One of the major factors determining MCT is the ciliary
      activity of the respiratory epithelium. Rhinoscintigraphy is the most commonly
      used method for the analysis of mucociliary activity. The aim of this study was
      to investigate the effect of facial paralysis on the nasal mucociliary clearance.
      MATERIALS AND METHODS: This study included 38 Bell's palsy patients as the study
      group and 10 subjects without any history of paranasal sinus disease or facial
      paralysis as the control group. A drop of technetium 99m-labeled macroaggregated
      albumin (Tc-99m MAA) was placed posterior to the head of the inferior turbinate
      and followed with a gamma camera. MCT rate was measured as the velocity of Tc-99m
      MAA drop. RESULTS: The mean MCT rate was 4.27 +/- 0.76 millimeters per minute
      (mm/min) on 20 sides of 10 healthy controls, 4.11 +/- 2.91 mm/min on the affected
      sides of the patients with Bell's palsy, and 6.03 +/- 3.13 mm/min on the
      nonparalyzed sides of the patients. MCT rate was statistically significantly
      faster in the nonparalyzed side when compared to the paralyzed side in Bell's
      palsy patients (P = 0.001). MCT rates were not significantly different in the
      control group and paralyzed sides of the Bell's palsy patients (P = 0.810). The
      MCT rate was statistically significantly faster in the nonparalyzed sides of
      Bell's palsy patients when compared to the controls (P = 0.017). CONCLUSION: This
      study showed a faster MCT rate on the nonparalyzed side in Bell's palsy patients
      when compared to the paralyzed side and the control subjects. A compensatory
      mechanism could be the underlying reason for faster MCT on the nonparalyzed side.
      Further studies on larger patient groups are needed to investigate the effect of
      facial paralysis on the MCT and changes of facial nerve function on the opposite,
      nonparalyzed side of the face.

PMID- 27022801
TI  - Experience in the management of the mass casualty from the January 2010 Jos
      Crisis.
AB  - BACKGROUND: On the 17 of January 2010, a sectarian crisis broke out in Jos the
      capital of Plateau state, Nigeria. It created a mass casualty situation in the
      Jos University Teaching Hospital. We present the result of the hospital
      management of that mass casualty incident. OBJECTIVE: To share our experience in
      the management of the mass casualty situation arising from the sectarian crisis
      of Jos in January 2010. METHODOLOGY: We retrospectively reviewed the hospital
      records of patients who were treated in our hospital with injuries sustained in
      the Jos crisis of January 2010. RESULTS: A total of 168 patients presented over a
      four day period. There were 108 males (64.3%) and 60 females (35.7%). The mean
      age was 26 +/- 16 years. Injury was caused by gunshots in 68 patients (40.5%),
      machete in 56 (33.3%), falls in 22 (13.1%) and burning in 21 (13.1%). The body
      parts injured were the upper limbs in 61(36.3%) patients, lower limbs 44 (26.2%)
      and scalp 43 (25.6%). Majority, 125 (74.4%) did not require formal operative
      care. Fourteen (8.3%) patients had complications out of which 10 (6.0%) were
      related to infections. There were 5 (3.1%) hospital mortalities and the mean
      duration of hospital stay was 4.2 days. The hospital operations returned to
      routine 24 hours after the last patient was brought in. As a result of changes
      made to our protocol, management proceeded smoothly and there was no stoppage of
      the hospital response at any point. CONCLUSION: This civil crisis involved mostly
      young males. Injuries were mainly lacerations from machete and gunshot injuries.
      Majority of the victims did not require formal surgical operations beyond initial
      care. Maintaining continuity in the positions of the Incident commander and the
      mass casualty commander ensure a smooth disaster response with fewer challenges.

PMID- 27022802
TI  - Caregivers' perception of oral health-related quality of life in a group of
      Nigerian children living with human immunodeficiency virus.
AB  - AIM: This study examined the caregivers' perception of the effect of dental
      conditions on general well-being and family life of a group of human
      immunodeficiency virus (HIV)-infected Nigerian children. A secondary aim was to
      investigate correlations between the children's sociodemographic and health
      related variables and caregivers' global ratings of oral health and well-being.
      Study Design A cross-sectional questionnaire-based survey was conducted among
      parents/caregivers of 95 HIV-positive children receiving care at the Lagos State
      University Teaching Hospital, Nigeria. MATERIALS AND METHODS: The "Parental
      Caregivers Perception Questionnaire" which included measures of global ratings of
      oral health and well-being as well as effects of oral health on domains of oral
      symptoms, functional limitations, emotional well-being, and family well
      being/parental distress was used. Assessment was based on the child's oral health
      within the preceding 3 months of the study. RESULTS: The most affected subscale
      of the oral health-related quality of life was functional limitation followed by
      parental distress and then oral symptoms. Caregivers of older children were 21/2
      times more likely to view oral health as impacting their child's overall health
      (P = 0.034). Furthermore, caregivers of children who had not yet commenced
      antiretroviral therapy were 15% more likely to report oral symptoms (P = 0.024)
      and 11% were more likely to be distressed. STATISTICS: Data entry, validation,
      and analysis were done using SPSS version 17.0. Findings were considered to be
      statistically significant when 95% confidence intervals were not overlapping.
      CONCLUSIONS: According to caregivers' perceptions, oral symptoms, functional
      limitations, and parental distress outweighed emotional well-being in impacting a
      child's oral health quality of life. Oral health programs to improve the
      knowledge of caregivers on the importance of oral health in HIV-positive children
      are necessary for improvement in overall quality of life.

PMID- 27022803
TI  - Craniofacial orthodontics and postgraduate orthodontic training in Nigeria.
AB  - INTRODUCTION: Craniofacial orthodontics has been shown to be a critical component
      of the care of patients with craniofacial anomalies such as cleft lip and palate.
      Thus, the purpose of this study was to assess the perceptions and clinical
      experience in cleft and craniofacial care, of orthodontic residents in Nigeria.
      METHODOLOGY: Questionnaires were sent out to orthodontic residents in the six
      Postgraduate Orthodontic Training Centers in the country at that time. The
      questionnaires were self-administered and covered areas in beliefs in cleft care
      and the clinical experience and challenges faced by the residents in the
      provision of craniofacial orthodontic care at their various institutions.
      RESULTS: Thirty-three respondents returned completed questionnaires, with a
      response rate of 97%. All the respondents believed that residents should be
      involved in cleft and craniofacial care. Postnatal counseling was the clinical
      procedure in which the residents reported the highest level of clinical
      experience (47.4%). The least clinical experience was recorded in pre-bone graft
      orthodontics (7.4%) and orthodontic preparation for orthognathic surgery (5.5%).
      Some of the challenges highlighted by the residents were low patients turn out
      for orthodontic care and the absence of multidisciplinary treatment for
      craniofacial patients in their centers. CONCLUSION: Orthodontic residents in
      Nigeria believe that they should be involved in the management of patients with
      craniofacial anomalies and cleft lip and palate. However, majority of the
      residents have limited clinical experience in the management of these patients. A
      lot more needs to be done, to expose orthodontic residents in training, to all
      aspects of the orthodontic and multidisciplinary team care required for the
      cleft/craniofacial patient.

PMID- 27022804
TI  - Knowledge and attitudes of dentists toward shortened dental arch therapy in Saudi
      Arabia.
AB  - OBJECTIVE: The aim of this study was to assess and compare the knowledge and
      attitudes of dentists toward shortened dental arch (SDA) therapy in Saudi Arabia.
      MATERIALS AND METHODS: In this cross-sectional study, self-designed-structured
      questionnaires were distributed among specialists (SP), residents (RES), and
      general dental practitioners (GDP) in Saudi Arabia. The questionnaire enquired
      about dentists' opinion regarding function, esthetic, and comfort in patients
      with SDA. It also enquired about the risks associated with SDA treatment (tooth
      wear, temporomandibular dysfunction (TMD), and tooth migration). Participants
      also graded SDA decision-making factors for their significance. Frequency
      distribution and Chi-square test were performed to compare the responses.
      RESULTS: A total of 300 questionnaires were completed. 53.9% of SP applied SDA
      therapy in <10% of patients. However, 54.8% of RES and 46.6% of GDP never used
      SDA therapy. SDA was considered by dentists to provide a satisfactory or
      acceptable function (76.4%), esthetics (76.1%), and comfort (76.8%). There was a
      significant difference in opinions of SP, GDP, and RES, in relation to the effect
      of SDA on esthetics (P = 0.039), tooth-wear (P < 0.001), TMD (P < 0.001), and
      tooth migration (P = 0.002). CONCLUSION: The knowledge of SP and GDP with regards
      to SDA therapy was broadly in line with current standards. Less than 10% of
      patients had objections towards SDA therapy. SDA therapy was clinically applied
      in fewer than 10% of cases.

PMID- 27022805
TI  - Biomechanical analysis of titanium fixation plates and screws in mandibular angle
      fractures.
AB  - OBJECTIVE: The aim of this study was to evaluate the mechanical behavior of
      different rigid fixation methods in mandibular angle fractures. MATERIALS AND
      METHODS: Three different three-dimensional finite element models of the mandible
      were developed to simulate the biomechanical responses of titanium plates and
      screws. The fracture lines were fixed with double 4-hole straight, 4-hole square,
      and 5-hole Y plates with monocortical screws. 150 N incisal occlusal loads were
      simulated on the models. The commercial ANSYS software was utilized to calculate
      the Von Mises stresses on fixative appliances. RESULTS: The highest Von Mises
      stress values were observed in the Y plate, whereas the lowest stress values have
      been found in the square plate. CONCLUSIONS: The use of square plate led to
      better stability and lower mechanical stresses than other techniques.

PMID- 27022806
TI  - Odontogenic cervical necrotizing fasciitis, etiological aspects.
AB  - INTRODUCTION: Cervical necrotizing fasciitis is a rare but very severe infection
      that affects the soft-tissues of the cephalic extremity. Cervical necrotizing
      fasciitis most frequently occurs secondarily to inflammatory odontogenic
      disorders and represents the most severe infection of maxillofacial spaces, with
      a high lethal potential. MATERIALS AND METHODS: In this study, we selected 55
      patients with confirmed cervical necrotizing fasciitis of odontogenic origin,
      treated in the Clinic of Oral and Maxillofacial Surgery in Cluj-Napoca during
      January 1996-December 2012. RESULTS: In the majority of cases, the disease
      evolved without the presence of associated systemic disorders (60% [45.49
      72.69]), the rest of the patients having 1-4 types of systemic disorders; type 2
      diabetes mellitus was the most frequent type of underlying systemic disorder.
      From the appearance of the first symptoms until the presentation for treatment, a
      time interval of 2-30 days elapsed. During this time period, 78.18% (95%
      confidence interval [CI] [65.49-89.06]) of the patients received antibiotic
      treatment, but without results. Mandibular molars were the most frequent starting
      point of the disease, and the submandibular space was the first affected by the
      disease, 47.27% (95% CI [32.76-61.79]). Bacteriological exams showed that
      facultatively aerobic/anaerobic G + bacteria were the most frequently identified
      (72.22% [58.21-83.60]). CONCLUSION: The odontogenic lesions of the lower molars,
      complicated by submandibular space infections, are the most frequent starting
      point of odontogenic cervicofacial necrotizing fasciitis. Delayed surgical
      treatment and strict antibiotic therapy play an important role in favoring the
      development of odontogenic necrotizing fasciitis.

PMID- 27022807
TI  - Ocular disorders in stroke patients in a tertiary hospital in Nigeria.
AB  - BACKGROUND: Stroke is a medical emergency of public health importance which
      affects the physical, mental, and emotional well-being of its victims. Management
      and rehabilitation are cumbersome for patients and caregivers. Ocular involvement
      and visual loss could further increase the burden of care. AIM: To determine the
      prevalence of ocular disorders in patients with stroke in a Tertiary Hospital in
      Nigeria. MATERIALS AND METHODS: A descriptive hospital-based study was performed
      on all consenting and conscious adult patients aged 18 years and above with a
      diagnosis of stroke made within 1-year who were admitted to the stroke ward or
      attended the stroke clinic of the Neurology Unit in the Department of Medicine,
      University of Benin Teaching Hospital, Benin City from October 2013 to December
      2013. RESULTS: A total of 170 eyes of 85 patients were studied with a mean age of
      66.08 years +/- 10.99; range 43-88 years. There was a male: female ratio of
      2.6:1. Ocular abnormalities were documented in 95.5% of the patients. A
      presenting visual acuity of >=6/18 was found in 66.7%. Mild ptosis and exotropia
      were seen in 2.9% and 0.6% of the eyes respectively. Intraocular pressure was
      between 10-21 mmHg in 87.7% eyes while 11.8% eyes had afferent pupillary defects.
      Cataract was seen in 71.8% eyes and optic nerve head changes in 48.8% eyes which
      includes temporal disc pallor and glaucomatous optic neuropathy in 29.4% and
      14.2% eyes, respectively. Abnormalities found in the retina include retinal
      hemorrhages in 10.6% eyes, cotton wool spots in 2.4% eyes, and hard exudates in
      7.8% eyes. Retinal vascular abnormalities were documented in 32.4% eyes. Visual
      complaints following stroke were documented in 9.6% of the patients. CONCLUSION:
      Ocular abnormalities are present in patients with stroke, mostly due to
      predisposing risk factors for stroke, and age-related changes. Routine ophthalmic
      evaluation is suggested in the management of patients with cerebrovascular
      accident in our environment for better quality of care.

PMID- 27022808
TI  - Blood pressure to height ratio as a screening tool for prehypertension and
      hypertension in adolescents.
AB  - BACKGROUND: Current methods of detection of childhood hypertension are cumbersome
      and contribute to under-diagnosis hence, the need to generate simpler diagnostic
      tools. The blood pressure to height ratio has recently been proposed as a novel
      screening tool for prehypertension and hypertension in some populations. We
      evaluated its applicability in our environment. MATERIALS AND METHODS: The
      weights, heights, and blood pressure measurements of 2364 apparently healthy
      adolescents were determined. Sex-specific systolic and diastolic blood pressure
      to height ratios (SBPHR) and (DBPHR) were calculated, and their ability to detect
      prehypertension and hypertension was determined using receiver operating curves.
      Discriminatory ability was measured by the area under the curve (AUC) and optimal
      cutoff points along the curve were determined. P < 0.05 was considered
      statistically significant. RESULTS: The SBPHR and DBPHR were similar across all
      age groups and sexes. The AUC of SBPHR and DBPHR for diagnosing prehypertension
      and hypertension by sex was >0.95 for both diastolic and systolic hypertension in
      both sexes. It ranged between 0.803 and 0.922 for prehypertension and 0.954-0.978
      for hypertension indicating higher accuracy for hypertension. Sensitivity was
      higher for systolic and diastolic hypertension (90-98%) compared with
      prehypertension (87-98%). Specificity was lower than sensitivity across all
      categories of hypertension and prehypertension (0.64-0.88%) though higher for
      hypertension (0.75-0.88) compared with prehypertension (0.64-0.75). CONCLUSION:
      BPHR is a useful screening tool for prehypertension and hypertension in black
      adolescents. Accuracy increased with higher degrees of hypertension.

PMID- 27022809
TI  - Acute and intermittent testicular torsion: Analysis of presentation, management,
      and outcome in South East, Nigeria.
AB  - BACKGROUND: Testicular torsion compromises the blood supply to the testes and may
      result in testicular loss or damage if not dealt with promptly. It can occur
      either as acute testicular torsion (ATT) or intermittent testicular torsion
      (ITT). This study examines the presentation, management, and outcome of adult
      testicular torsion. PATIENTS AND METHODS: During the period January 1999 and
      December 2009, 34 out of 59 patients treated for testicular torsion, who had
      complete records, were evaluated. Operating theater and urology ward admission
      registers were used to identify patients. RESULTS: Age range was 16-50 years. Of
      the 34 patients, 11 (32.4%) were between 26 and 30 years old, while 16 (47.1%)
      were between 16 and 25 years old. Mean age was 27 years. Scrotal pain of varying
      severity was noted in all patients; there was associated vomiting in 21% of cases
      and abdominal pain in 38% of cases. Clinical diagnosis was ATT in 12 (35.3%)
      patients and ITT in 22 (64.7%) patients. In the ATT group, only one patient
      (8.3%) presented within 6 h of onset of symptoms. In the ITT group, 3 patients
      (13.6%) presented within 1 month of onset of symptoms while 7 (31.8%) of patients
      presented between 1 and 6 months after the onset of symptoms. Testicular salvage
      rate was 58.3% for ATT. Surgical intervention occurred within 3 h in the ATT
      group in 7 patients (58.3%) and in 5 patients (41.7%) within 3-6 h of onset of
      symptoms. In the patients with ITT, 12 patients (54.5%) were operated upon within
      1 month of presentation. Preoperative external manual detorsion was performed in
      1 patient. CONCLUSION: Late presentation was observed, especially in the
      intermittent variety. Delay occurred both at pre- and intra-hospital phases.
      Testicular salvage rate may be improved by physician/health worker and community
      enlightenment. Adoption of local anesthetic may reduce intrahospital delay.

PMID- 27022810
TI  - Retrograde jejunal intussusception after total gastrectomy: A case report and
      literature review.
AB  - Retrograde jejunal intussusception is a rare disease. A 60-year-old female
      patient was hospitalized due to vomiting for 2 days, with a history of radical
      gastrectomy plus esophagus jejunum Rouxs-en-Y. On examination, there was a
      palpable wax-like mass on the left-hand side underneath the umbilicus.
      Computerized tomography scan showed a proximal jejunal intussusception. During
      surgery, the distal jejunum was found set into the proximal jejunum for a length
      of 30 cm, and bowel necrosis was also observed. The necrotic tube was resected
      and anastomosis was performed. Four days after the surgery, gastrointestinal
      function resumed. After a 10-month follow-up, the patient had no discomfort. 

PMID- 27022811
TI  - Case report of giant sialolith (megalith) of the Wharton's duct.
AB  - Sialolithiasis is the most common disease of salivary glands. Its estimated
      frequency is 1.2% in the adult population. Sialoliths most commonly occur in the
      submandibular glands. The sublingual gland and minor salivary glands are rarely
      affected. The sialolith usually measures from 1 to <10 mm. Giant sialoliths are
      classified as those exceeding 15 mm in any one dimension. In literature, large
      sialoliths or megalith (> mm) of Wharton's duct have rarely been reported. This
      case report describes a patient presenting with an unusually large sialolith
      (megalith) of Wharton's duct, which was 37 mm *16 mm in the size, the subsequent
      patient management, the etiology, diagnosis, and its treatment. 

PMID- 27022812
TI  - Endoscopic resection of an esophageal leiomyoma with overlying dysplasia without
      specialized equipment.
AB  - Leiomyomas are rare benign esophageal tumors. Association of this subepithelial
      lesion with abnormal epithelium is rarer. Endoscopic mucosal resection is an
      alternative to surgery for removing suitable mucosal and submucosal lesions from
      the gastrointestinal tract. This procedure is seldom performed in developing
      countries due to limited equipment and expertise. We describe a case of
      esophageal leiomyoma with overlying dysplasia in the mid esophagus that was
      completely removed endoscopically in a developing country without the standard
      accessory equipment. Traditional thoracotomy would have been associated with
      higher cost and morbidity. 

PMID- 27022813
TI  - Anchor balloons assisted deep intubation of 5F catheters for uncrossable lesions.
AB  - A number of treatment strategies for complex coronary lesions have been utilized
      in varying clinical settings over the last decade. However, cardiologists still
      encounter some difficult scenarios such as variant coronary artery origins,
      severely calcified and highly tortuous lesions. We report four cases in which the
      stents failed to cross lesions using the conventional percutaneous coronary
      intervention techniques, but all the target lesions were successfully stented
      finally using a new combined technique of anchor balloon assisted deep intubation
      of 5F "child-in-mother" catheter. 

PMID- 27022814
TI  - Isolated Fournier's gangrene of the penis.
AB  - To share experience on the presentation and management of 4 cases of isolated
      penile Fournier's gangrene. Clinical and demographic data of four patients with
      isolated penile Fournier's gangrene seen over an 8-year period (January 2006
      December 2013) were reviewed. All patients had intravenous fluid resuscitation,
      emergency surgical debridement, and broad-spectrum intravenous antibiotics.
      Fournier's gangrene of the penis was, respectively, due to long segment anterior
      urethral stricture, penile edema from poorly controlled congestive cardiac
      failure, penile abrasion from oral sex and idiopathic. The mean age of the
      patients was 34.3 +/- 5.6 years. One patient with urethral stricture had urinary
      tract infection. The patients presented with a prodromal period of genital pain
      and fever followed by genital swelling, gangrene, and ulceration. The most common
      wound swab isolates were Staphylococcus aureus and Escherichia coli. Only the
      skin and dartos fascia were affected with sparing of the corporal cylinders. Mean
      hospital stay was 17.3 +/- 3.0 days and mean Fournier's gangrene severity index
      (FGSI) was 4.0 +/- 0.8. Wound closure was achieved by split skin grafting in 2
      patients, delayed primary closure in the third and healing by secondary intention
      in the fourth patient. Subjectively assessed erectile function was preserved in
      all four patients. Isolated Fournier's gangrene of the penis is very rare. It is
      associated with low FGSI and sparing of the three corporal cylinders. It may
      rarely follow oral sexual practice. 

PMID- 27022815
TI  - Intestinal endometriosis. Our experience.
AB  - Intestinal endometriosis is defined as a bowel infiltration by ectopic
      endometrial tissue. The prevalence is 3-37% of all women affected by
      endometriosis. Rectosigmoid colon is the most frequent location (70-93%),
      followed to ileocecal region, appendix and other colon and small bowel segments.
      Intestinal endometriosis usually is asymptomatic. Often it is only diagnosed
      during surgery for other reasons. The symptoms frequently are nonspecific,
      although it may appear as an acute abdominal pain. Clinical history, physical
      examination and image techniques are necessary for the diagnosis. The choice of
      the operative technique depends on the clinical presentation and on the fertility
      wishes of the patient. Laparotomy and laparoscopy are equally effective, but
      laparoscopic approach is preferred. We present 17 cases of patients from our
      Hospital diagnosed with intestinal endometriosis, from 2006 to 2015. 

PMID- 27022816
TI  - The patient with anemia.
AB  - PURPOSE OF REVIEW: Anemia remains a global health issue. This review addresses
      the recent findings on anemia in surgical patients and its significance in
      perioperative setting. RECENT FINDINGS: The prevalence of anemia in surgical
      populations is high, ranging from one-third of population to nearly 100%. Anemia
      is an independent, modifiable risk factor for a growing list of unfavorable
      events, complications and diminished functional outcomes (lasting for months
      following discharge), as well as a major predisposing factor for allogeneic blood
      transfusions. Therefore, timely screening and diagnosis of anemia prior to
      elective surgeries is of great importance. Nonetheless, studies suggest that many
      opportunities to properly manage anemia in perioperative setting are lost.
      Patient blood management provides a framework of evidence-based strategies to
      effectively reduce the risk of occurrence of anemia and treat it with the
      ultimate goal of improving patient outcomes. Studies on the clinical impact of
      patient blood management strategies are emerging. SUMMARY: Active screening for
      anemia and proper management of it in perioperative setting is essential. Several
      strategies to prevent anemia - including elimination of unnecessary diagnostic
      blood draws - are effective and reasonable approaches.

PMID- 27022817
TI  - Anesthesia for off-floor dental and oral surgery.
AB  - PURPOSE OF REVIEW: Anesthesia for dentistry is commonly performed outside the
      operating room. The combination of a shared airway between surgeon and
      anesthetist, the variety of open airway techniques, and the out-of-operating room
      setting often results in anxiety and avoidance of dental cases among anesthesia
      personnel. This review attempts to demystify dental treatment and facilitate the
      anesthesia provider in providing effective sedation of dental procedures
      performed in the nonoperating room setting. RECENT FINDINGS: Specific indications
      for dental anesthesia improve the patient selection process. Airway assessment
      and strategies to secure the difficult airway are paramount because of the nature
      of the procedures and the patients on whom they are performed. Pediatric patients
      and those with special needs present specific preanesthetic assessment,
      induction, and management challenges. Emergence delirium is disruptive, possibly
      dangerous, prolongs recovery time, and may necessitate hospitalization.
      Simplified techniques and objective recovery criteria are necessary to ensure a
      safe and smooth discharge to home. Airway fire precautions should not be
      overlooked given the rare but potential risk of airway fire during dental
      treatment. SUMMARY: This article reviews the indications, facility and equipment
      needs, monitoring requirements, treatment methods, and recovery protocols
      necessary for the safe administration of off-floor anesthesia for dentistry.

PMID- 27022818
TI  - My name or yours? Event-related potential correlates of self-name processing.
AB  - This electrophysiological study examined the roles of self-specificity
      (designating the participant: 'me' vs. 'not-me'), self-relevance (degree of
      relevance to the participant: high self-relevance vs. less self-relevance), and
      familiarity (the frequency of occurrence in daily routine: high familiarity vs.
      less familiarity) in the preferential processing of self-name (SN) by comparing
      the processing of SN (i.e. the participant's name being of 'me', high self
      relevance and high familiarity) with the processing of a close other's name (CON)
      (e.g. the participant's father's name being of 'not-me', high self-relevance and
      high familiarity), a famous person's name (FPN) (e.g. a politician's name being
      of 'not-me', less self-relevance and less familiarity), and an unknown name (UN)
      (e.g. a stranger's name being of 'not-me', self-irrelevance and unfamiliarity).
      Participants were asked to complete an implicit task (i.e. to judge the color of
      the name stimuli). This study found that SN elicited larger N170 amplitudes than
      all other names, whereas there were no differences between its amplitudes
      elicited by all other names. There were no differences between P300 amplitudes
      elicited by SN and CON, whereas the above two names elicited larger P300
      amplitudes than FPN and UN. These findings suggest that the preferential
      processing of SN is not only because of self-relevance and familiarity that could
      differentiate between names with high self-relevance and high familiarity (i.e.
      SN and CON) and names with less self-relevance/self-irrelevance and less
      familiarity/unfamiliarity (i.e. FPN and UN) but also because of self-specificity
      that could differentiate between SN and all other names. 

PMID- 27022819
TI  - Nicotine excites corticotropin-releasing hormone mRNA-expressing neuron in the
      hypothalamic paraventricular nucleus in vitro in rats.
AB  - Nicotine is known to modulate the activity of the hypothalamic-pituitary-adrenal
      axis by stimulating corticotropin-releasing hormone (CRH) release from the
      hypothalamic paraventricular nucleus (PVN). However, the mechanism by which
      nicotine affects the hypothalamic-pituitary-adrenal axis by modulating PVN CRH
      neuronal activity is currently unclear. Here, we examined the effects of nicotine
      on PVN CRH-mRNA-expressing neurons in vitro in rats by whole-cell patch-clamp
      recordings, biocytin staining, and single-cell reverse transcription-multiplex
      PCR techniques. Of the 146 PVN putative parvocellular neurons, 17.1% (25/146)
      coexpressed GAPDH mRNA and CRH mRNA. Under current-clamp recording conditions,
      application of nicotine (1 MUM) induced excitation in 92% (23/25) PVN CRH-mRNA
      expressing neurons, which showed a significant increase in the spike firing rate
      accompanied by a depolarization of the membrane potential. Nicotine induced an
      increase in the spike firing rate of PVN CRH-mRNA-expressing neurons in a
      concentration-dependent manner. The half-effective concentration (EC50) of
      nicotine for increasing the spike firing rate of PVN CRH-mRNA-expressing neurons
      was 1.6 MUM. Extracellular application of ionotropic glutamate receptor
      antagonist kynurenic acid (1 mM) abolished the nicotine-induced excitation of PVN
      CRH-mRNA-expressing neurons. Moreover, application of nicotine induced a
      significant increase in the spontaneous excitatory postsynaptic currents
      frequency, but without significantly altering the spontaneous excitatory
      postsynaptic currents amplitude of the CRH-mRNA-expressing neurons. Biocytin
      staining confirmed that the nicotine-sensitive CRH-mRNA-expressing neurons were
      located in the PVN parvocellular division. These results indicated that
      extracellular administration of nicotine indirectly excited PVN CRH-mRNA
      expressing neurons, suggesting that nicotine modulated PVN CRH secretion by
      enhancement of both the presynaptic action potential drive and quantal glutamate
      release.

PMID- 27022820
TI  - Current advances in therapies for osteoarthritis.
AB  - PURPOSE OF REVIEW: Although osteoarthritis (OA) has received a paucity of
      attention from researchers in terms of drug development, there have been some
      significant findings relevant to clinical issues in OA that are summarized in
      this review. RECENT FINDINGS: Recent osteoarthritis research has focused on
      synovial, subchondral bone, and biomechanical effects of the disease. Results
      from a pilot study of patients treated with methotrexate demonstrated 20% pain
      reduction in 50% of patients and 40% pain reduction in 37% of patients. Data show
      that plasma levels of interleukin-1 receptor antagonist and synovial fluid levels
      of interleukin-6 and tumor necrosis factor-alpha associate with radiographic
      progression, suggesting that these mediators may be prognostic biomarkers and/or
      targets for drug development. Recent data suggest that subchondral bone features
      associate with structural progression, suggesting a need for therapeutic
      approaches that target this region. Patient-reported outcome measures and
      kinematic factors may predict success to an exercise treatment protocol and
      unloader braces appear to reduce the knee adduction moment, suggesting a need for
      a comprehensive review of the clinical effects of braces. SUMMARY: Advances in
      the understanding of key areas of osteoarthritis pathogenesis are helping define
      the spectrum of therapeutic targets that potentially should be explored to reduce
      the symptomatic and structural effects of osteoarthritis.

PMID- 27022823
TI  - Frosting on the cake: pictures on food packaging bias serving size.
AB  - OBJECTIVE: Food packaging often pictures supplementary extras, such as toppings
      or frosting, that are not listed on the nutritional labelling. The present study
      aimed to assess if these extras might exaggerate how many calories? are pictured
      and if they lead consumers to overserve. DESIGN: Four studies were conducted in
      the context of fifty-one different cake mixes. For these cake mixes, Study 1
      compared the calories stated on the nutrition label with the calories of the cake
      (and frosting) pictured on the box. In Studies 2, 3 and 4, undergraduates
      (Studies 2 and 3) or food-service professionals (Study 4) were given one of these
      typical cake mix boxes, with some being told that cake frosting was not included
      on the nutritional labelling whereas others were provided with no additional
      information. They were then asked to indicate what they believed to be a
      reasonable serving size of cake. Settings Laboratory setting. SUBJECTS:
      Undergraduate students and food-service professionals. RESULTS: Study 1 showed
      that the average calories of cake and frosting pictured on the package of fifty
      one different cake mixes exceed the calories on the nutritional label by 134 %.
      Studies 2 and 3 showed that informing consumers that the nutritional information
      does not include frosting reduces how much people serve. Study 4 showed that even
      food-service professionals overserve if not told that frosting is not included on
      the nutritional labelling. CONCLUSIONS: To be less misleading, packaging should
      either not depict extras in its pictures or it should more boldly and clearly
      state that extras are not included in calorie counts.

PMID- 27022824
TI  - PARP inhibitors: the race is on.

PMID- 27022825
TI  - Long-term impact of liver function on curative therapy for hepatocellular
      carcinoma: application of the ALBI grade.
AB  - BACKGROUND: Application of curative therapy for hepatocellular carcinoma is
      crucially dependent on underlying liver function. Using the recently described
      ALBI grade we examined the long-term impact of liver dysfunction on survival of
      early-stage hepatocellular carcinoma (HCC) patients. METHODS: This cohort study
      comprised 2559 HCC patients from different geographic regions, all treated with
      curative intent. We also examined the relation between indocyanine green (ICG)
      clearance and ALBI score. Survival was measured from the date of treatment to the
      date of death or last follow-up. RESULTS: The ALBI score correlated well with ICG
      clearance. Among those undergoing surgical resection, patients with ALBI grade-1
      (good liver function) survived approximately twice as long as those with ALBI
      grade-2 (less good liver function), although more than 90% of these patients were
      classified as Child-Pugh (C-P) grade A. In the cohort receiving ablative
      therapies, there was a similar difference in survival between ALBI grade-1 and
      grade-2. Cox regression analysis confirmed that the ALBI score along with age,
      gender, aetiology and tumour factors (AFP, tumour size/number and vascular
      invasion) independently influenced survival in HCC patients receiving curative
      treatments. CONCLUSIONS: The ALBI score represents a simple approach to the
      assessment of liver function in patients with HCC. After potentially curative
      therapy, those with ALBI grade-1 survived approximately twice as long as those
      with ALBI grade-2. These data suggest that ALBI grade-1 patients are
      appropriately treated with surgical resection whereas ALBI grade-2 patients may,
      where the option exists, be more suitable for liver transplantation or the less
      invasive curative ablative therapies.

PMID- 27022827
TI  - Corrigendum: Giant barocaloric effect in hexagonal Ni2In-type Mn-Co-Ge-In
      compounds around room temperature.

PMID- 27022826
TI  - Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and
      metastatic pancreatic cancer.
AB  - BACKGROUND: Modifications of FOLFIRINOX are widely used despite the absence of
      prospective data validating efficacy in metastatic disease (metastatic pancreatic
      cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a
      multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer
      to assess the impact of dose attenuation in MPC and efficacy in LAPC. METHODS:
      Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and
      bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with
      full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS)
      and median overall survival (OS) were determined. RESULTS: In total, 31 and 44
      patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of
      modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months
      (95% CI 7.65-14.32) and PFS 6.1 months (95% CI 5.19-8.31). In LAPC, efficacy was
      notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0-23.9)
      and OS 26.6 months (95% CI 16.7, NA). Neutropenia (P<0.0001), vomiting (P<0.001)
      and fatigue (P=0.01) were significantly decreased. [(18)F]-Fluorodeoxyglucose
      positron emission tomography imaging response did not correlate with PFS or OS.
      CONCLUSIONS: In this first prospective study of modified FOLFIRINOX in MPC and
      LAPC, we observed decreased AEs compared with historical control patients. In
      MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were
      prolonged and support the continued use of FOLFIRINOX in this setting.

PMID- 27022828
TI  - Isolation and Characterization of Single Cells from Zebrafish Embryos.
AB  - The zebrafish (Danio rerio) is a powerful model organism to study vertebrate
      development. Though many aspects of zebrafish embryonic development have been
      described at the morphological level, little is known about the molecular basis
      of cellular changes that occur as the organism develops. With recent advancements
      in microfluidics and multiplexing technologies, it is now possible to
      characterize gene expression in single cells. This allows for investigation of
      heterogeneity between individual cells of specific cell populations to identify
      and classify cell subtypes, characterize intermediate states that occur during
      cell differentiation, and explore differential cellular responses to stimuli.
      This study describes a protocol to isolate viable, single cells from zebrafish
      embryos for high throughput multiplexing assays. This method may be rapidly
      applied to any zebrafish embryonic cell type with fluorescent markers. An
      extension of this method may also be used in combination with high throughput
      sequencing technologies to fully characterize the transcriptome of single cells.
      As proof of principle, the relative abundance of cardiac differentiation markers
      was assessed in isolated, single cells derived from nkx2.5 positive cardiac
      progenitors. By evaluation of gene expression at the single cell level and at a
      single time point, the data support a model in which cardiac progenitors coexist
      with differentiating progeny. The method and work flow described here is broadly
      applicable to the zebrafish research community, requiring only a labeled
      transgenic fish line and access to microfluidics technologies. 

PMID- 27022829
TI  - Qualitative Characterization of the Aqueous Fraction from Hydrothermal
      Liquefaction of Algae Using 2D Gas Chromatography with Time-of-flight Mass
      Spectrometry.
AB  - Two-dimensional gas chromatography coupled with time-of-flight mass spectrometry
      is a powerful tool for identifying and quantifying chemical components in complex
      mixtures. It is often used to analyze gasoline, jet fuel, diesel, bio-diesel and
      the organic fraction of bio-crude/bio-oil. In most of those analyses, the first
      dimension of separation is non-polar, followed by a polar separation. The aqueous
      fractions of bio-crude and other aqueous samples from biofuels production have
      been examined with similar column combinations. However, sample preparation
      techniques such as derivatization, solvent extraction, and solid-phase extraction
      were necessary prior to analysis. In this study, aqueous fractions obtained from
      the hydrothermal liquefaction of algae were characterized by two-dimensional gas
      chromatography coupled with time-of-flight mass spectrometry without prior sample
      preparation techniques using a polar separation in the first dimension followed
      by a non-polar separation in the second. Two-dimensional plots from this analysis
      were compared with those obtained from the more traditional column configuration.
      Results from qualitative characterization of the aqueous fractions of algal bio
      crude are discussed in detail. The advantages of using a polar separation
      followed by a non-polar separation for characterization of organics in aqueous
      samples by two-dimensional gas chromatography coupled with time-of-flight mass
      spectrometry are highlighted. 

PMID- 27022830
TI  - Microscopy of Fission Yeast Sexual Lifecycle.
AB  - The fission yeast Schizosaccharomyces pombe has been an invaluable model system
      in studying the regulation of the mitotic cell cycle progression, the mechanics
      of cell division and cell polarity. Furthermore, classical experiments on its
      sexual reproduction have yielded results pivotal to current understanding of DNA
      recombination and meiosis. More recent analysis of fission yeast mating has
      raised interesting questions on extrinsic stimuli response mechanisms, polarized
      cell growth and cell-cell fusion. To study these topics in detail we have
      developed a simple protocol for microscopy of the entire sexual lifecycle. The
      method described here is easily adjusted to study specific mating stages.
      Briefly, after being grown to exponential phase in a nitrogen-rich medium, cell
      cultures are shifted to a nitrogen-deprived medium for periods of time suited to
      the stage of the sexual lifecycle that will be explored. Cells are then mounted
      on custom, easily built agarose pad chambers for imaging. This approach allows
      cells to be monitored from the onset of mating to the final formation of spores. 

PMID- 27022831
TI  - In Vitro Corrosion and Cytocompatibility of a Microarc Oxidation Coating and
      Poly(L-lactic acid) Composite Coating on Mg-1Li-1Ca Alloy for Orthopedic
      Implants.
AB  - Manipulating the degradation rate of biomedical magnesium alloys poses a
      challenge. The characteristics of a microarc oxidation (MAO), prepared in phytic
      acid, and poly(L-lactic acid) (PLLA) composite coating, fabricated on a novel Mg
      1Li-1Ca alloy, were studied through field emission scanning electron microscopy
      (FE-SEM), electron probe X-ray microanalysis (EPMA), energy dispersive X-ray
      spectroscopy (EDS) and X-ray diffraction (XRD). The corrosion behaviors of the
      samples were evaluated via hydrogen evolution, potentiodynamic polarization and
      electrochemical impedance spectroscopy in Hanks' solution. The results indicated
      that the MAO/PLLA composite coatings significantly enhanced the corrosion
      resistance of the Mg-1Li-1Ca alloy. MTT and ALP assays using MC3T3 osteoblasts
      indicated that the MAO/PLLA coatings greatly improved the cytocompatibility, and
      the morphology of the cells cultured on different samples exhibited good
      adhesion. Hemolysis tests showed that the composite coatings endowed the Mg-1Li
      1Ca alloys with a low hemolysis ratio. The increased solution pH resulting from
      the corrosion of magnesium could be tailored by the degradation of PLLA. The
      degradation mechanism of the composite coatings was discussed. The MAO/PLLA
      composite coating may be appropriate for applications on degradable Mg-based
      orthopedic implants.

PMID- 27022832
TI  - Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic
      Nanoscopy.
AB  - Direct polymerization of an oxaliplatin analogue was used to reproducibly
      generate amphiphiles in one pot, which consistently and spontaneously self
      assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage
      in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin
      in cell culture experiments. We investigated this phenomenon by super-resolution
      fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion
      mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are
      taken up via endocytic pathways before intracellular release of their cytotoxic
      cargo. As with other drug-carrying nanomaterials, these systems have potential as
      cellular delivery vehicles. However, high-resolution methods to track
      nanocarriers and their cargo at the micro- and nanoscale have been underutilized
      in general, limiting our understanding of their interactions with cells and
      tissues. We contend this type of combined optical and isotopic imaging strategy
      represents a powerful and potentially generalizable methodology for cellular
      tracking of nanocarriers and their cargo.

PMID- 27022833
TI  - Quantitative Monitoring of Microphase Separation Behaviors in Cationic Liposomes
      Using HHC, DPH, and Laurdan: Estimation of the Local Electrostatic Potentials in
      Microdomains.
AB  - Microphase separation behaviors of cationic liposomes have been investigated
      using a pH-sensitive fluorescent probe with 4-heptadecyl-7-hydroxycoumarin (HHC),
      1,6-diphenyl-1,3,5-hexatriene, and 6-lauroyl-2-dimethylaminonaphthalene, and to
      estimate localized electrostatic potentials. Shifts of the apparent pKa values of
      HHC were observed in cationic liposomes in proportion to the amount of cationic
      lipids. Two pKa values were obtained with 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC)/3beta-[N(N',N'-dimethylaminoethane)-carbamoyl] cholesterol
      hydrochloride (DC-Ch) liposomes, while only one pKa value was generated with
      either DOPC/1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or
      DOPC/dimethyldioctadecylammonium-bromide (DODAB) liposomes. The physicochemical
      membrane property analyses, focusing on membrane fluidity and membrane polarity,
      revealed heterogeneity among DOPC/DC-Ch liposomes. By analyzing the pH titration
      curves using sigmoidal fitting, the localized electrostatic potentials were
      estimated. For DOPC/DOTAP = (7/3), the membrane was in the liquid-disordered
      phase and the density of cationic molecules was 0.41 cation/nm(2). For DOPC/DC-Ch
      = (7/3), the membrane was heterogeneous and the densities of cationic molecules
      in liquid-disordered and liquid-ordered phases were 0.25 and 1.24 cation/nm(2),
      respectively. We thereby conclude that the DC-Ch molecules can form nanodomains
      when these molecules are concentrated to 59%. 

PMID- 27022822
TI  - Development and Validation of a Prediction Rule for Benefit and Harm of Dual
      Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention.
AB  - IMPORTANCE: Dual antiplatelet therapy after percutaneous coronary intervention
      (PCI) reduces ischemia but increases bleeding. OBJECTIVE: To develop a clinical
      decision tool to identify patients expected to derive benefit vs harm from
      continuing thienopyridine beyond 1 year after PCI. DESIGN, SETTING, AND
      PARTICIPANTS: Among 11,648 randomized DAPT Study patients from 11 countries
      (August 2009-May 2014), a prediction rule was derived stratifying patients into
      groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI.
      Validation was internal via bootstrap resampling and external among 8136 patients
      from 36 countries randomized in the PROTECT trial (June 2007-July 2014).
      EXPOSURES: Twelve months of open-label thienopyridine plus aspirin, then
      randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus
      aspirin. MAIN OUTCOMES AND MEASURES: Ischemia (myocardial infarction or stent
      thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI. RESULTS:
      Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women,
      25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%).
      Derivation cohort models predicting ischemia and bleeding had c statistics of
      0.70 and 0.68, respectively. The prediction rule assigned 1 point each for
      myocardial infarction at presentation, prior myocardial infarction or PCI,
      diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2
      points each for history of congestive heart failure/low ejection fraction and
      vein graft intervention; -1 point for age 65 to younger than 75 years; and -2
      points for age 75 years or older. Among the high score group (score >=2, n =
      5917), continued thienopyridine vs placebo was associated with reduced ischemic
      events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P <
      .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, 
      0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely,
      continued thienopyridine was associated with smaller increases in bleeding among
      the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26)
      compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%],
      P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean
      age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and
      bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for
      bleeding. In this cohort, the high-score patients (n = 2848) had increased
      ischemic events compared with the low-score patients and no significant
      difference in bleeding. CONCLUSION AND RELEVANCE: Among patients not sustaining
      major bleeding or ischemic events 1 year after PCI, a prediction rule assessing
      late ischemic and bleeding risks to inform dual antiplatelet therapy duration
      showed modest accuracy in derivation and validation cohorts. This rule requires
      further prospective evaluation to assess potential effects on patient care, as
      well as validation in other cohorts. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00977938.

PMID- 27022834
TI  - Revealing the Reconstructed Surface of Li[Mn2]O4.
AB  - The spinel Li[Mn2]O4 is a candidate cathode for a Li-ion battery, but its
      capacity fades over a charge/discharge cycle of Li1-x[Mn2]O4 (0 < x < 1) that is
      associated with a loss of Mn to the organic-liquid electrolyte. It is known that
      the disproportionation reaction 2Mn(3+) = Mn(2+) + Mn(4+) occurs at the surface
      of a Mn spinel, and it is important to understand the atomic structure and
      composition of the surface of Li[Mn2]O4 in order to understand how Mn loss
      occurs. We report a study of the surface reconstruction of Li[Mn2]O4 by
      aberration-corrected scanning transmission electron microscopy. The atomic
      structure coupled with Mn-valence and the distribution of the atomic ratio of
      oxygen obtained by electron energy loss spectroscopy reveals a thin, stable
      surface layer of Mn3O4, a subsurface region of Li1+x[Mn2]O4 with retention of
      bulk Li[Mn2]O4. This observation is compatible with the disproportionation
      reaction coupled with oxygen deficiency and a displacement of surface Li(+) from
      the Mn3O4 surface phase. These results provide a critical step toward
      understanding how Mn is lost from Li[Mn2]O4, once inside a battery.

PMID- 27022835
TI  - Polyphenol-Aluminum Complex Formation: Implications for Aluminum Tolerance in
      Plants.
AB  - Natural polyphenols may play an important role in aluminum detoxification in some
      plants. We examined the interaction between Al(3+) and the purified high
      molecular weight polyphenols pentagalloyl glucose (940 Da) and oenothein B (1568
      Da), and the related compound methyl gallate (184 Da) at pH 4 and 6. We used
      spectrophotometric titration and chemometric modeling to determine stability
      constants and stoichiometries for the aluminum-phenol (AlL) complexes. The
      structures and spectral features of aluminum-methyl gallate complexes were
      evaluated with quantum chemical calculations. The high molecular weight
      polyphenols formed Al3L2 complexes with conditional stability constants (beta) ~
      1 * 10(23) at pH 6 and AlL complexes with beta ~ 1 * 10(5) at pH 4. Methyl
      gallate formed AlL complexes with beta = 1 * 10(6) at pH 6 but did not complex
      aluminum at pH 4. At intermediate metal-to-polyphenol ratios, high molecular
      weight polyphenols formed insoluble Al complexes but methyl gallate complexes
      were soluble. The high molecular weight polyphenols have high affinities and
      solubility features that are favorable for a role in aluminum detoxification in
      the environment. 

PMID- 27022836
TI  - Tunable Molecular MoS2 Edge-Site Mimics for Catalytic Hydrogen Production.
AB  - Molybdenum sulfides represent state-of-the-art, non-platinum electrocatalysts for
      the hydrogen evolution reaction (HER). According to the Sabatier principle, the
      hydrogen binding strength to the edge active sites should be neither too strong
      nor too weak. Therefore, it is of interest to develop a molecular motif that
      mimics the catalytic sites structurally and possesses tunable electronic
      properties that influence the hydrogen binding strength. Furthermore, molecular
      mimics will be important for providing mechanistic insight toward the HER with
      molybdenum sulfide catalysts. In this work, a modular method to tune the
      catalytic properties of the S-S bond in MoO(S2)2L2 complexes is described. We
      studied the homogeneous electrocatalytic hydrogen production performance metrics
      of three catalysts with different bipyridine substitutions. By varying the
      electron-donating abilities, we present the first demonstration of using the
      ligand to tune the catalytic properties of the S-S bond in molecular MoS2 edge
      site mimics. This work can shed light on the relationship between the structure
      and electrocatalytic activity of molecular MoS2 catalysts and thus is of broad
      importance from catalytic hydrogen production to biological enzyme functions. 

PMID- 27022838
TI  - Copper-Catalyzed C(sp(2))-H Difluoroalkylation of Aldehyde Derived Hydrazones
      with Diboron as Reductant.
AB  - An efficient and general method for C(sp(2))-H difluoroalkylation of aldehyde
      derived hydrazones via a Cu(II)/B2pin2-catalyzed reaction between difluoroalkyl
      bromides and hydrazones was developed. In this reaction, both aromatic and
      aliphatic difluoroalkylated aldehyde derived hydrazones could be achieved in good
      to excellent yields. For some heteroaromatic aldehyde derived hydrazones, two
      fluoroacetates could be introduced onto the final products. A preliminary
      mechanism study manifested that a difluoroalkyl radical via SET pathway was
      involved in the reaction. In addition, the catalytic diboron reagent plays an
      indispensable role in this transformation.

PMID- 27022839
TI  - Endoscopic ultrasound-guided tissue acquisition: does the needle make the
      difference?

PMID- 27022837
TI  - Discovery of an Orally Active and Liver-Targeted Prodrug of 5-Fluoro-2'
      Deoxyuridine for the Treatment of Hepatocellular Carcinoma.
AB  - We report a series of novel O-(substituted benzyl) phosphoramidate prodrugs of 5
      fluoro-2'-deoxyuridine for the treatment of hepatocellular carcinoma. Through
      structure optimization, the o-methylbenzyl analog (1t) was identified as an
      orally bioavailable and liver-targeted lead compound. This lead prodrug is well
      tolerated at a dose up to 3 g/kg in Kuming mice via oral administration. An
      efficacy study demonstrated that it possesses good inhibitory effect (61.67% and
      72.50%, respectively) on tumor growth in a mouse xenograft model. A metabolism
      study in Sprague-Dawley rats suggested that 1t can release the desired 5'
      monophosphate in the liver with high liver-targeting index.

PMID- 27022840
TI  - Confocal laser endomicroscopy for functional barrier imaging in Crohn's disease.

PMID- 27022841
TI  - Adverse events with non-anesthesiologist administration of propofol: what you see
      is what you get but getting (the right standard monitors) is how you see.

PMID- 27022842
TI  - Reply to White et al.

PMID- 27022845
TI  - [French comment on article: Dual-focus versus conventional magnificationendoscopy
      for the diagnosis of superficial squamous neoplasms in the pharynx and esophagus:
      a randomized trial].

PMID- 27022846
TI  - [French comment on article: A randomized trial comparing multiband mucosectomy
      and cap-assisted endoscopic resection for endoscopic piecemeal resection of early
      squamous neoplasia of the esophagus].

PMID- 27022847
TI  - [French comment on article: A meta-analysis comparing ProCore and standard fine
      needle aspiration needles for endoscopic ultrasound-guided tissue acquisition].

PMID- 27022848
TI  - [French comment on article: Balloon catheter versus basket catheter for
      endoscopic bile duct stone extraction: a multicenter randomized trial].

PMID- 27022849
TI  - [French comment on article: ERCP practitioners in China: results from national
      surveys in 2007 and 2013].

PMID- 27022850
TI  - [French comment on article: Confocal laser endomicroscopy: a novel method for
      prediction of relapse in Crohn's disease].

PMID- 27022851
TI  - [French comment on article: Use of the patency capsule in patients with
      established Crohn's disease undergoing video capsule endoscopy of the small
      bowel].

PMID- 27022852
TI  - Video Comment on Karstensen et al.

PMID- 27022853
TI  - GP and pharmacist inter-professional learning - a grounded theory study.
AB  - BACKGROUND: Practice Based Small Group Learning (PBSGL) is an established
      learning resource for primary care clinicians in Scotland and is used by one
      third of general practitioners (GPs). Scottish Government and UK professional
      bodies have called for GPs and pharmacists to work more closely together to
      improve care. AIM: To gain GPs' and pharmacists' perceptions and experiences of
      learning together in an inter-professional PBSGL pilot. DESIGN AND SETTING:
      Qualitative research methods involving established GP PBSGL groups in NHS
      Scotland recruiting one or two pharmacists to join them. METHOD: A grounded
      theory method was used. GPs were interviewed in focus groups by a fellow GP, and
      pharmacists were interviewed individually by two researchers, neither being a GP
      or a pharmacist. Interviews were audio-recorded, transcribed and analysed using
      grounded theory methods. Data saturation was achieved and confirmed. RESULTS AND
      CONCLUSION: Three themes were identified: GPs' and pharmacists' perceptions and
      experiences of inter-professional learning; Inter-professional relationships and
      team-working; Group identity and purpose of existing GP groups. Pharmacists were
      welcomed into GP groups and both professions valued inter-professional PBSGL
      learning. Participants learned from each other and both professions gained a
      wider perspective of the NHS and of each others' roles in the organisation. Inter
      professional relationships, communication and team-working were strengthened and
      professionals regarded each other as peers and friends.

PMID- 27022854
TI  - Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment
      in a Transgenic Rat Model of Alzheimer's Disease with Stroke.
AB  - Alzheimer's disease (AD) is a debilitating neurodegenerative disease that results
      in neurodegeneration and memory loss. While age is a major risk factor for AD,
      stroke has also been implicated as a risk factor and an exacerbating factor. The
      co-morbidity of stroke and AD results in worsened stroke-related motor control
      and AD-related cognitive deficits when compared to each condition alone. To model
      the combined condition of stroke and AD, a novel transgenic rat model of AD, with
      a mutated form of amyloid precursor protein (a key protein involved in the
      development of AD) incorporated into its DNA, is given a small unilateral
      striatal stroke. For a model with the combination of both stroke and AD,
      behavioral tests that assess stroke-related motor control, locomotion and AD
      related cognitive function must be implemented. The cylinder task involves a cost
      efficient, multipurpose apparatus that assesses spontaneous forelimb motor use.
      In this task, a rat is placed in a cylindrical apparatus, where the rat will
      spontaneously rear and contact the wall of the cylinder with its forelimbs. These
      contacts are considered forelimb motor use and quantified during video analysis
      after testing. Another cost-efficient motor task implemented is the beam-walk
      task, which assesses forelimb control, hindlimb control and locomotion. This task
      involves a rat walking across a wooden beam allowing for the assessment of limb
      motor control through analysis of forelimb slips, hindlimb slips and falls.
      Assessment of learning and memory is completed with Morris water maze for this
      behavioral paradigm. The protocol starts with spatial learning, whereby the rat
      locates a stationary hidden platform. After spatial learning, the platform is
      removed and both short-term and long-term spatial reference memory is assessed.
      All three of these tasks are sensitive to behavioral differences and completed
      within 28 days for this model, making this paradigm time-efficient and cost
      efficient. 

PMID- 27022855
TI  - Iodine-125-labeled DNA-Triplex-forming oligonucleotides reveal increased cyto-
      and genotoxic effectiveness compared to Phosphorus-32.
AB  - PURPOSE: The efficacy of DNA-targeting radionuclide therapies might be strongly
      enhanced by employing short range particle-emitters. However, the gain of
      effectiveness is not yet well substantiated. We compared the Auger electron
      emitter I-125 to the beta--emitter P-32 in terms of biological effectiveness per
      decay and radiation dose when located in the close proximity to DNA using DNA
      Triplex-forming oligonucleotides (TFO). The clonogenicity and the induction of
      DNA double-strand breaks (DSB) were investigated in SCL-II cells after exposure
      to P-32- or I-125-labeled TFO targeting the glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) gene and after external homogeneous exposure to gamma-rays
      as reference radiation. MATERIALS AND METHODS: TFO were labeled with P-32 or I
      125 using the primer extension method. Cell survival was analyzed by colony
      forming assay and DNA damage was assessed by microscopic quantification of
      protein 53 binding protein 1 (53BP1) foci in SCL-II cells. RESULTS: I-125-TFO
      induced a pronounced decrease of cell survival (D37 at ~360 accumulated decays
      per cell, equivalent to 1.22 Gy cell nucleus dose) and a significant increase of
      53BP1 foci with increasing decays. The P-32-labeled TFO induced neither a strong
      decrease of cell survival nor an increase of 53BP1 foci up to ~4000 accumulated
      decays per cell, equivalent to ~1 Gy cell nucleus dose. The RBE for I-125-TFO was
      in the range of 3-4 for both biological endpoints. CONCLUSIONS: I-125-TFO proved
      to be much more radiotoxic than P-32-TFO per decay and per unit dose although
      targeting the same sequence in the GAPDH gene. This might be well explained by
      the high number of low energy Auger electrons emitted by I-125 per decay, leading
      to a high ionization density in the immediate vicinity of the decay site,
      probably producing highly complex DNA lesions overcharging DNA repair mechanisms.

PMID- 27022856
TI  - Field Surveys and Experimental Transmission of Pleurogonius malaclemys (Digenea:
      Pronocephalidae), an Intestinal Parasite of the Diamondback Terrapin Malaclemys
      terrapin.
AB  - :  Life history stages of Pleurogonius malaclemys were investigated in wild
      populations of the eastern mudsnail ( Ilyanassa obsoleta ) and diamondback
      terrapin ( Malaclemys terrapin ) in New Jersey, New York, and Rhode Island
      between 2011 and 2015, and laboratory experiments investigating the settling
      preference of metacercarial cysts of P. malaclemys were conducted. Cysts of P.
      malaclemys were found on mudsnails on the north and south shores of Long Island,
      New York and in Rhode Island, approximately 280 km farther north than previously
      reported. The cysts were found on mudsnails year round, but cyst prevalence
      increased during the summer months, reaching maximum levels (~70%) in November.
      Nearly 58% of Jamaica Bay, New York mudsnails had cysts; mean intensities were
      2.63 cysts/mudsnail. Although cyst prevalence was high, only 11 mudsnails (0.28%)
      were found to have the internal redial stages of P. malaclemys, the stage of
      infection preceding external cysts. In addition to mudsnails, P. malaclemys could
      encyst on other biological substrates, including common terrapin prey species.
      The majority of wild adult terrapins from Stone Harbor, New Jersey were infected
      with the adult stage of P. malaclemys (80.30%, x- = 36.36 trematodes/terrapin, n
      = 66). Juvenile terrapins were experimentally infected with P. malaclemys and on
      average 22.5% of the consumed cysts successfully developed into adult trematodes.
      Studies on the life cycle of P. malaclemys are important because previous
      research has shown that the frequency of cysts of P. malaclemys on mudsnails can
      be used as an indirect measure of terrapin abundance.

PMID- 27022857
TI  - Effect of Utipro((r)) (containing gelatin-xyloglucan) against Escherichia coli
      invasion of intestinal epithelial cells: results of an in vitro study.
AB  - AIM: To evaluate whether Utipro((r)), a natural product approved to prevent
      urinary tract infections, protects intestinal epithelial cells from Escherichia
      coli adherence/intracellular invasion in vitro. MATERIALS & METHODS: Caco-2 and
      CacoGoblet(TM) cells were treated with Utipro (1.5 to 10 mg/ml) or untreated
      (controls). E. coli adherence/intracellular invasion was evaluated by Trans
      Epithelial Electrical Resistance, Lucifer Yellow assay and microbial counts.
      RESULTS: Utipro was noncytotoxic. Utipro 5 and 10 mg/ml protected cell tight
      junctions (mean +/- SD Trans-Epithelial Electrical Resistance [Omega * cm(2)]
      66.83 +/- 0.29 and 71.33 +/- 0.29, respectively), and protected cells from E.
      coli intracellular invasion (mean +/- SD reductions in total bacteria counts
      [Log10] 0.9 +/- 0.06 and 2.1 +/- 0.56, respectively). CONCLUSION: Results
      indicate that Utipro creates a protective physical barrier on intestinal
      epithelial cells in vitro which reduces the settling of E. coli reservoirs. These
      results constitute the first step in the demonstration of the efficacy of Utipro
      to prevent urinary tract infections. Further research is needed in in vivo models
      and clinical trials.

PMID- 27022858
TI  - MR Imaging Measures of Intracranial Atherosclerosis in a Population-based Study.
AB  - Purpose To implement a magnetic resonance (MR) imaging protocol to measure
      intracranial atherosclerotic disease (ICAD) in a population-based multicenter
      study and report examination and reader reliability of these MR imaging
      measurements and descriptive statistics representative of the general population.
      Materials and Methods This prospective study was approved by the institutional
      review boards and compliant with HIPAA. Atherosclerosis Risk in Communities
      (ARIC) study participants (n = 1980) underwent brain MR imaging from 2011 to 2013
      at four ARIC sites. Imaging included three-dimensional black-blood MR imaging and
      time-of-flight MR angiography. One hundred two participants returned for repeat
      MR imaging to estimate examination and reader variability. Plaque presence
      according to vessel segment was recorded. Quantitative measurements included
      lumen size and degree of stenosis, wall and/or plaque thickness, area and volume,
      and normalized wall index for each vessel segment. Reliability was assessed with
      percentage agreement, kappa statistics, and intraclass correlation coefficients.
      Results Of the 1980 participants, 1755 (mean age, 77.6 years; 1026 women [59%];
      1234 white [70%]) completed examinations with adequate to excellent image
      quality. The weighted ICAD prevalence was 34.4% (637 of 1755 participants) and
      was higher in men than women (38.5% [302 of 729 participants] vs 31.7% [335 of
      1026 participants], respectively; P = .012) and in African Americans compared
      with whites (41.1% [215 of 518 participants] vs 32.4% [422 of 1234 participants],
      respectively; P = .002). Percentage agreement of plaque identification per
      participant was 87.0% (interreader estimate), 89.2% (intrareader estimate), and
      89.9% (examination estimate). Examination and reader reliability ranged from fair
      to good (kappa, 0.50-0.78) for plaque presence and from good to excellent
      (intraclass correlation coefficient, 0.69-0.99) for quantitative vessel wall
      measurements. Conclusion Vessel wall MR imaging is a reliable tool for
      identifying and measuring ICAD and provided insight into ICAD distribution across
      a U.S. community-based population. ((c)) RSNA, 2016 Online supplemental material
      is available for this article.

PMID- 27022860
TI  - Search for fungi-specific metabolites of four model drugs in postmortem blood as
      potential indicators of postmortem fungal metabolism.
AB  - Fungi colonizing cadavers are capable of drug metabolism and may thus change the
      metabolite pattern or concentration of drugs in forensic postmortem samples. The
      purpose of this study was to check for the presence of such changes by searching
      fungi-specific metabolites of four model drugs (amitriptyline, metoprolol,
      mirtazapine, and zolpidem) in decomposed postmortem blood samples from 33 cases
      involving these drugs. After isolation and identification of fungal strains
      present in the samples, each isolate was incubated in Sabouraud medium at 25
      degrees C for up to 120h with each model drug. One part of the supernatants was
      directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS),
      another after liquid-liquid extraction with chlorobutane and concentration. From
      21 out of 33 decomposed postmortem blood samples (64%) a total of 30 different
      strains could be isolated, one from the class of Ascomycete and the rest
      belonging to 15 species from 8 different genera (number of species): Aspergillus
      (2), Botrytis (1), Candida (8), Fusarium (1), Mucor (1), Penicillium (1), and
      Rodothorula (1). In the in vitro studies, these microorganisms were found capable
      of N-demethylation and N-oxidation of amitriptyline and mirtazapine, O
      demethylation followed by side chain oxidation of metoprolol as well as
      hydroxylation of all four-model drugs. In two of the postmortem blood samples,
      from which the fungi Aspergillus jensenii, Candida parapsilosis. and Mucor
      circinelloides had been isolated, a fungi-specific hydroxy zolpidem metabolite
      was detected. The presence of this metabolite in postmortem samples likely
      indicates postmortem fungal biodegradation. 

PMID- 27022859
TI  - Bone marrow adipose tissue: formation, function and regulation.
AB  - The human body requires an uninterrupted supply of energy to maintain metabolic
      homeostasis and energy balance. To sustain energy balance, excess consumed
      calories are stored as glycogen, triglycerides and protein, allowing the body to
      continue to function in states of starvation and increased energy expenditure.
      Adipose tissue provides the largest natural store of excess calories as
      triglycerides and plays an important role as an endocrine organ in energy
      homeostasis and beyond. This short review is intended to detail the current
      knowledge of the formation and role of bone marrow adipose tissue (MAT), a
      largely ignored adipose depot, focussing on the role of MAT as an endocrine organ
      and highlighting the pharmacological agents that regulate MAT.

PMID- 27022861
TI  - Improvement and automation of a real-time PCR assay for vaginal fluids.
AB  - The identification of vaginal fluids is crucial in forensic science. Several
      molecular protocols based on PCR amplification of mfDNA (microflora DNA) specific
      for vaginal bacteria are now available. Unfortunately mfDNA extraction and PCR
      reactions require manual optimization of several steps. The aim of present study
      was the verification of a partial automatization of vaginal fluids identification
      through two instruments widely diffused in forensic laboratories: EZ1 Advanced
      robot and Rotor Gene Q 5Plex HRM. Moreover, taking advantage of 5-plex
      thermocycler technology, the ForFluid kit performances were improved by expanding
      the mfDNA characterization panel with a new bacterial target for vaginal fluids
      and with an internal positive control (IPC) to monitor PCR inhibition. Results
      underlined the feasibility of a semi-automated extraction of mfDNA using a
      BioRobot and demonstrated the analytical improvements of the kit. 

PMID- 27022862
TI  - Conversation Game Effectively Engages Groups of Individuals in Discussions about
      Death and Dying.
AB  - BACKGROUND: Discussions about end-of-life (EOL) values, wishes, and beliefs are
      critical for effective advance care planning (ACP). New strategies are needed to
      engage individuals in EOL conversations. OBJECTIVE: The study objective was to
      test the feasibility of using a conversation game to engage individuals in EOL
      discussions. METHODS: This study used a mixed-methods approach. Participants
      played a conversation game that prompts players to answer and discuss 20
      questions about death, dying, and EOL care. Participants completed pre- and
      postgame questionnaires and participated in postgame focus groups. Subjects were
      70 healthy volunteers (18 groups of families, friends, or strangers).
      Demographics, emotional state, and perceived relational closeness were measured
      using preintervention questionnaires. Postintervention questionnaires measured
      conversation satisfaction, realism, self-rated quality, and emotional state.
      Postgame focus groups evaluated players' experiences playing the game. RESULTS:
      Using a seven-point Likert scale (1 = low score, 7 = high score), players rated
      game conversations as satisfying (mean [M] = 6.1, SD = 0.9), realistic (M = 5.6,
      SD = 0.8), and of high quality (M = 5.7, SD = 0.9). There were no negative
      effects on emotional state immediately postgame (M = 1.3, SD = 0.5). A thematic
      analysis of participants' experiences (n = 55) revealed that (1) playing the game
      was an enjoyable, positive experience; (2) a game is a good framing for EOL
      discussions; and (3) there were mixed opinions about ideal game group
      composition. CONCLUSIONS: This study established that healthy volunteers enjoyed
      engaging in a two-hour discussion about EOL issues when framed as a game. The
      game experience was a positive, satisfying, and enjoyable activity for
      participants. Further studies are needed to determine if health games can promote
      effective ACP.

PMID- 27022863
TI  - Peptide-incorporated 3D porous alginate scaffolds with enhanced osteogenesis for
      bone tissue engineering.
AB  - Good bioactivity and osteogenesis of three-dimensional porous alginate scaffolds
      (PAS) are critical for bone tissue engineering. In this work, alginate and bone
      forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7 (BMP-7),
      have been combined together (without carbodiimide chemistry treatment) to develop
      peptide-incorporated PAS (p-PAS) for promoting bone repairing ability. The
      mechanical properties and SEM images show no difference between pure PAS and p
      PAS. The release kinetics of the labeled peptide with 6-carboxy tetramethyl
      rhodamine from the PAS matrix suggests that the peptide is released in a
      relatively sustained manner. In the cell experiment, p-PAS show higher cell
      adhesion, spreading, proliferation and alkaline phosphatase (ALP) activity than
      the pristine PAS group, indicating that the BFP-1 released from p-PAS could
      significantly promote the aggregation and differentiation of osteoblasts,
      especially at 10MUg/mL of trapped peptide concentration (p-PAS-10). Furthermore,
      p-PAS-10 was implanted into Beagle calvarial defects and bone regeneration was
      analyzed after 4 weeks. New bone formation was assessed by calcein and Masson's
      trichrome staining. The data reveal that p-PAS group exhibits significantly
      enhanced oseto-regenerative capability in vivo. The peptide-modified PAS with
      promoted bioactivity and osteogenic differentiation in vitro as well as bone
      formation ability in vivo could be promising tissue engineering materials for
      repairing and regeneration of bone defects. 

PMID- 27022864
TI  - Optimization and characterization of a homogeneous carboxylic surface
      functionalization for silicon-based biosensing.
AB  - A well-organized immobilization of bio-receptors is a crucial goal in biosensing,
      especially to achieve high reproducibility, sensitivity and specificity. These
      requirements are usually attained with a controlled chemical/biochemical
      functionalization that creates a stable layer on a sensor surface. In this work,
      a chemical modification protocol for silicon-based surfaces to be applied in
      biosensing devices is presented. An anhydrous silanization step through 3
      aminopropylsilane (APTES), followed by a further derivatization with succinic
      anhydride (SA), is optimized to generate an ordered flat layer of carboxylic
      groups. The properties of APTES/SA modified surface were compared with a
      functionalization in which glutaraldehyde (GA) is used as crosslinker instead of
      SA, in order to have a comparison with an established and largely applied
      procedure. Moreover, a functionalization based on the controlled deposition of a
      plasma polymerized acrylic acid (PPAA) thin film was used as a reference for
      carboxylic reactivity. Advantages and drawbacks of the considered methods are
      highlighted, through physico-chemical characterizations (OCA, XPS, and AFM) and
      by means of a functional Protein G/Antibody immunoassay. These analyses reveal
      that the most homogeneous, reproducible and active surface is achieved by using
      the optimized APTES/SA coupling. 

PMID- 27022865
TI  - Codelivery of doxorubicin-containing thermosensitive hydrogels incorporated with
      docetaxel-loaded mixed micelles enhances local cancer therapy.
AB  - Doxorubicin (DOX) thermosensitive hydrogels (TSHs) incorporated with docetaxel
      (DOC)-loaded mixed micelles were developed to co-deliver these two drugs through
      a TSH system, DH700kMF-13.5/M-DocLF, to improve local cancer therapy and reduce
      side effects. First, Pluronics-based DOC-loaded mixed micelles were developed and
      optimized. The optimal formulation designated as M-DocLF was composed of 1mg/g
      docetaxel, 15mg/g Pluronic F127 (PF127), and 45mg/g Pluronic L121 (PL121).
      Rheological tests showed that DH700kMF-13.5/M-DocLF was an injectable flowing
      solution, which formed a nonflowing gel at body temperature. After intratumoral
      (IT) or peritumoral (PT) administration, DH700kMF-13.5/M-DocLF demonstrated
      efficient growth inhibition of CT-26 tumors in a Balb/c mice model. The tumor
      inhibitory rate after IT administration of DH700kMF-13.5/M-DocLF was 92.4%,
      followed by 85.8%, 75.6%, 62.9%, 50.6%, and 49.5% for DH700kMF-15, free DOX, F
      13.5/M-DocLF, Tynen (DOC solution), and M-DocLF, respectively. Furthermore, PT
      administration of DH700kMF-13.5/M-DocLF resulted in similar efficacies.
      Pharmacokinetic and biodistribution studies showed that after subcutaneous (SC)
      and IT administration of the designated formulations, smaller amounts of DOX and
      DOC were absorbed from the local SC or tumor sites into systemic circulation,
      probably reducing their systemic toxicity. Tumor retention of DOX and DOC in
      biodistribution studies further revealed that co-delivery of these two drugs in
      DH700KMF-13.5/M-DocLF potentially enhanced the efficacy of tumor inhibition. In
      conclusion, our in situ injectable DOX and DOC TSH is a potential dual drug
      delivery system, which can enhance the efficacy of cancer chemotherapy with
      minimal side effects and reduced chemoresistance. 

PMID- 27022866
TI  - Graphene oxide-wrapped PEGylated liquid crystalline nanoparticles for effective
      chemo-photothermal therapy of metastatic prostate cancer cells.
AB  - Here, we report the preparation of PEGylated liquid crystalline nanoparticles
      (LCN) loaded with docetaxel (DTX) and wrapped with graphene oxide (GO), called
      PEG-GO/LCN/DTX, for effective chemo-photothermal therapy of metastatic prostate
      cancer cells. The prepared formulation exhibited a small particle size (<250 nm),
      high drug loading capacity (~15%), and efficient near infrared (NIR) light
      induced thermal heat. Importantly, PEG-GO/LCN/DTX successfully accumulated in
      prostate cancer cells and exhibited potent apoptotic and antimigration effects,
      mediated by the combination of the anticancer effects of DTX and the thermal heat
      induced by exposure of GO to NIR light. Taken together, our findings support that
      PEG-GO/LCN/DTX may be an effective system for treatment of metastatic prostate
      cancer. Moreover, the results establish a proof-of-concept for the potential
      chemo-photothermal functionality of PEG-GO/LCN/DTX. This hybrid system of LCN and
      GO could provide controlled and targeted drug delivery with enhanced NIR-induced
      thermal effects for effective treatment of metastatic cancers. 

PMID- 27022867
TI  - Chitosan-modified lipid nanovesicles for efficient systemic delivery of l
      asparaginase.
AB  - The goal of this study was to evaluate the enhanced catalytic activity, increased
      stability, in vitro anti-cancer effects on H446 cells and in vivo bioavailability
      of novel enzyme delivery nanovesicles (l-asparaginase containing chitosan
      modified lipid nanovesicles, ACLNs) when administered intravenously. It was the
      first time for the chitosan-modified lipid nanovesicles to be fabricated to
      deliver l-asparaginase (ASP, a therapeutic enzyme) efficiently. It was indicated
      that ACLNs markedly increased the enzymatic activity, improved the
      temperature/acid-base/proteolytic stabilities and favorably changed the in vivo
      kinetic characteristics. Moreover, ACLNs exhibited higher anti-lung-cancer
      activity than free ASP. The possible existence status of ASP in ACLNs and the
      fluorescence changes of ACLNs reflecting the conformational changes after heat
      treatment were preliminary explored. ACLNs might be novel promising nanovesicles
      for effective systemic delivery of therapeutic enzyme ASP. 

PMID- 27022868
TI  - One-pot construction of boronate ester based pH-responsive micelle for combined
      cancer therapy.
AB  - In this study, one-pot strategy for the construction of micelles loaded with two
      types of anticancer drugs (i.e., doxorubicin and methotrexate) together is
      reported. On the basis of the reaction between boronic acid and 1,2-diol to form
      boronate ester, the formation of amphiphiles, their self-assembly into micelles
      and drug encapsulation occurs simultaneously under simple dialysis at the
      appropriate pH condition. In the one-pot strategy, the micelle yield is high
      (78.2%) and the drug encapsulation efficiency of the two drugs is improved
      compared with that of the traditional method. The micelles can selectively
      increase the drug release ratio at acidic pH, showing the pH-responsive behavior
      inherited from the property of boronate ester. By combining doxorubicin and
      methotrexate, the half-maximum inhibition concentrations of the two drugs are
      obviously reduced, showing synergistic efficacy against cancer cells. This
      strategy is promising and may be expanded to various applications. 

PMID- 27022869
TI  - Increased resistance to detachment of adherent microspheres and Bacillus spores
      subjected to a drying step.
AB  - In various environments, including that of food processing, adherent bacteria are
      often subjected to drying conditions. These conditions have been shown to result
      in changes in the ability of biofilms to cross-contaminate food in contact with
      them. In this study, we investigated the consequences of a drying step on the
      further ability of adherent bacterial spores to resist detachment. An initial
      series of experiment was set up with latex microspheres as a model. A microsphere
      suspension was deposited on a glass slide and incubated at 25, 35 and 50 degrees
      C for times ranging from 1h to 48h. By subjecting the dried slides to increasing
      water flow rates, we showed that both time and temperature affected the ease of
      microsphere detachment. Similar observations were made for three Bacillus spores
      despite differences in their surface properties, especially regarding their
      surface physicochemistry. The differences in ease of adherent spore detachment
      could not be clearly linked to the minor changes in spore morphology, observed
      after drying in various environmental conditions. In order to explain the
      increased interaction between spheres or spores and glass slides, the authors
      made several assumptions regarding the possible underlying mechanisms: the shape
      of the liquid bridge between the sphere and the substratum, which is greatly
      influenced by the hydrophilic/hydrophobic characters of both surfaces; the
      accumulation of soil at the liquid/air interface; the presence of trapped nano
      bubbles around and/or under the sphere. 

PMID- 27022870
TI  - Inhalable polymer-glycerosomes as safe and effective carriers for rifampicin
      delivery to the lungs.
AB  - Rifampicin loaded glycerosomes, vesicles composed of phospholipids, glycerol and
      water, were combined with trimethyl chitosan chloride (TMC) to prepare TMC
      glycerosomes or, alternatively, with sodium hyaluronate (HY) to obtain HY
      glycerosomes. These new hybrid nanovesicles were tested as carriers for pulmonary
      delivery of rifampicin. Glycerosomes without polymers were also prepared and
      characterized. All vesicles were similar: they were spherical, multilamellar and
      able to incorporate good amount of rifampicin (EE%~55%). The addition of the
      polymers to the formulations allowed an increase of mean diameter. All the
      glycerosomes, in particular HY-glycerosomes, were able to deliver the drug to the
      furthest stages of the Next Generation Impactor and the aptitude of the vesicles
      to be nebulized was always higher than that of drug dispersion. Rifampicin
      nanoincorporation in vesicles reduced the in vitro drug toxicity on A549 cells,
      as well as increased its efficacy against Staphylococcus aureus. Finally, the in
      vivo biodistribution and accumulation, evaluated after intra-tracheal
      administration to rats, confirmed the improvement of rifampicin accumulation in
      lungs. 

PMID- 27022871
TI  - Influence of protein bulk properties on membrane surface coverage during
      immobilization.
AB  - Biomolecules immobilization is a key factor for many biotechnological
      applications. For this purpose, the covalent immobilization of bovine serum
      albumin (BSA), lipase from Candida rugosa and protein G on differently
      functionalized regenerated cellulose membranes was investigated. Dynamic light
      scattering and electrophoresis measurements carried out on biomolecules in
      solution indicated the presence of monomers, dimers and trimers for both BSA and
      protein G, while large aggregates were observed for lipase. The immobilization
      rate and the surface coverage on functionalized regenerated cellulose membranes
      were studied as a function of biomolecule concentration. Results indicated that
      the saturation coverage of BSA and protein G was concentration independent
      (immobilized protein amount of 2.40+/-0.03mg/g and 2.65+/-0.07mg/g,
      respectively). Otherwise, a different immobilization kinetics trend was obtained
      for lipase, for which the immobilized amount increases as a function of time
      without reaching a saturation value. Atomic force microscopy (AFM) micrographs
      showed the formation of monolayers for both BSA and protein G on the membrane
      surface, while a multilayer structure is found for lipase, in agreement with the
      trends observed in the related immobilization kinetics. As a result, the
      morphology of the proteins layer on the membrane surface seems to be strictly
      dependent on the proteins behavior in solution. Besides, the surface coverage has
      been described for BSA and protein G by the pseudo second order models, the
      results indicating the surface reaction as the controlling step of immobilization
      kinetics. Finally, enzyme activity and binding capacity studies indicated the
      preservation of the biomolecule functional properties. 

PMID- 27022872
TI  - Plant plasma membrane aquaporins in natural vesicles as potential stabilizers and
      carriers of glucosinolates.
AB  - Their biodegradable nature and ability to target cells make biological vesicles
      potential nanocarriers for bioactives delivery. In this work, the interaction
      between proteoliposomes enriched in aquaporins derived from broccoli plants and
      the glucosinolates was evaluated. The vesicles were stored at different
      temperatures and their integrity was studied. Determination of glucosinolates,
      showed that indolic glucosinolates were more sensitive to degradation in aqueous
      solution than aliphatic glucosinolates. Glucoraphanin was stabilized by leaf and
      root proteoliposomes at 25 degrees C through their interaction with aquaporins.
      An extensive hydrogen bond network, including different aquaporin residues, and
      hydrophobic interactions, as a consequence of the interaction between the linear
      alkane chain of glucoraphanin and Glu31 and Leu34 protein residues, were
      established as the main stabilizing elements. Combined our results showed that
      plasma membrane vesicles from leaf and root tissues of broccoli plants may be
      considered as suitable carriers for glucosinolate which stabilization can be
      potentially attributed to aquaporins. 

PMID- 27022873
TI  - A comparative study of curcumin-loaded lipid-based nanocarriers in the treatment
      of inflammatory bowel disease.
AB  - Selective drug delivery to inflamed tissues is of widespread interest for the
      treatment of inflammatory bowel disease (IBD). Because a lack of physiological
      lipids has been described in patients suffering IBD, and some lipids present
      immunomodulatory properties, we hypothesize that the combination of lipids and
      anti-inflammatory drugs together within a nanocarrier may be a valuable strategy
      for overcoming IBD. In the present study, we investigated and compared the in
      vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin
      (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced
      colitis model. These nanocarriers included self-nanoemulsifying drug delivery
      systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell
      protamine nanocapsules (NC). In vitro, a 30-fold higher CC permeability across
      Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC>SNEDDS>NLC
      and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension
      significantly reduced TNF-alpha secretion by LPS-activated macrophages (J774
      cells). In vivo, only CC NLC were able to significantly decrease neutrophil
      infiltration and TNF-alpha secretion and, thus, colonic inflammation. Our results
      show that a higher CC permeability does not correlate with a higher efficacy in
      IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC
      retention at the intestinal site, rather than increased CC permeability are
      efficient treatments of IBD. 

PMID- 27022874
TI  - Development of intranasal nanovehicles of itraconazole and their immunological
      activities for the therapy of rhinovirus infection.
AB  - Itraconazole (ITZ)-loaded microemulsion (ME) systems for intranasal (IN) delivery
      were developed for the treatment of human rhinovirus serotype 1B (HRV1B)
      infection. ITZ was incorporated into the oil-in-water (o/w) ME formulation
      composed of benzyl alcohol (oil), Cremophor EL (surfactant), Solutol HS15
      (cosurfactant), and water. The optimized composition of ME was determined by
      constructing pseudo-ternary phase diagram. ITZ ME formulation with about 150nm
      mean diameter and spherical shape was prepared and the solubility of ITZ in blank
      ME was markedly improved (up to 13.9mg/mL). The initial value of droplet size was
      maintained with four times dilution in the aqueous buffer and 72h incubation.
      Released amounts of drug from ME formulation were significantly enhanced compared
      to drug suspension group (p<0.05). Particularly, ITZ ME group displayed lower
      levels of inflammatory markers in the lung compared to ITZ suspension group after
      their IN administration in the HRV1B-infected mouse model (p<0.05). Developed ITZ
      ME formulation via IN route can be a promising candidate for the treatment of
      rhinovirus infection. 

PMID- 27022875
TI  - Antibacterial modification of an injectable, biodegradable, non-cytotoxic block
      copolymer-based physical gel with body temperature-stimulated sol-gel transition
      and controlled drug release.
AB  - Biomaterials are being extensively used in various biomedical fields; however,
      they are readily infected with microorganisms, thus posing a serious threat to
      the public health care. We herein presented a facile route to the antibacterial
      modification of an important A-B-A type biomaterial using poly (ethylene glycol)
      methyl ether (mPEG)- poly(epsilon-caprolactone) (PCL)-mPEG as a typical model.
      Inexpensive, commercial bis(2-hydroxyethyl) methylammonium chloride (DMA) was
      adopted as an antibacterial unit. The effective synthesis of the antibacterial
      copolymer mPEG-PCL-~~~-PCL-mPEG (where ~~~ denotes the segment with DMA units)
      was well confirmed by FTIR and (1)H NMR spectra. At an appropriate modification
      extent, the DMA unit could render the copolymer mPEG-PCL-~~~-PCL-mPEG highly
      antibacterial, but did not largely alter its fascinating intrinsic properties
      including the thermosensitivity (e.g., the body temperature-induced sol-gel
      transition), non-cytotoxicity, and controlled drug release. A detailed study on
      the sol-gel-sol transition behavior of different copolymers showed that an
      appropriate extent of modification with DMA retained a sol-gel-sol transition,
      despite the fact that a too high extent caused a loss of sol-gel-sol transition.
      The hydrophilic and hydrophobic balance between mPEG and PCL was most likely
      broken upon a high extent of quaternization due to a large disturbance effect of
      DMA units at a large quantity (as evidenced by the heavily depressed PCL segment
      crystallinity), and thus the micelle aggregation mechanism for the gel formation
      could not work anymore, along with the loss of the thermosensitivity. The work
      presented here is highly expected to be generalized for synthesis of various
      block copolymers with immunity to microorganisms. Light may also be shed on
      understanding the phase transition behavior of various multiblock copolymers. 

PMID- 27022876
TI  - pH-responsive targeted and controlled doxorubicin delivery using hyaluronic acid
      nanocarriers.
AB  - Biocompatible nanogels were prepared using thiol modified hyaluronic acid and
      diacrylated pluronic F127 polymer. A simple Michael type addition reaction of
      activated thiol groups on acrylate moiety lead to the formation of these
      nanogels, which were further effectively fabricated with an anticancer drug for
      evaluating sustained drug release approach. Nanogels prepared were of 150nm in
      diameter with a narrow size distribution pattern. DOX released from these
      nanogels showed a slow and sustained release at acidic pH 5.0 as compared to
      minimal release at physiological pH 7.4. Cytotoxicity data revealed the higher
      efficiency of DOX loaded nanogels as compared to free DOX in Hela cell lines.
      Cellular uptake images supported the cytotoxicity data and displayed DOX
      intercalation at nuclear level of cells. The sustained drug delivery system
      showed DOX release after 24h and continued thereafter without affecting normal
      cells. Based on these findings, such nanogel system may be useful for delivering
      anticancer drug without hampering their toxicity value over longer durations and
      reducing the total dose amount in anticancer therapy. 

PMID- 27022877
TI  - Silicone-stabilized liposomes as a possible novel nanostructural drug carrier.
AB  - Development of silicone stabilized liposomes which can serve as novel drug
      nanocarriers is presented. Silicone precursor 1,3,5,7
      tetramethylcyclotetrasiloxane (D4(H)) was introduced into the bilayer of the
      cationic liposomes prepared from egg yolk phosphatidylocholine (PC) and double
      tailed dimethyldioctadecylammonium bromide (DODAB). The silicone material was
      created inside of the liposomal bilayer in the base-catalyzed polycondensation
      process of the D4(H) what was confirmed employing (29)Si solid-state MAS NMR and
      FTIR measurements. Surfactant lysis experiments revealed that resulted systems
      can be effectively stabilized. Transmission electron microscopy (TEM) and dynamic
      light scattering (DLS) measurements demonstrated that the silicone-stabilized
      liposomes have typical lipid vesicle's morphology and mean hydrodynamic diameters
      in the range of about 110nm. They have considerably lower tendency for
      aggregation than the pristine liposomes. The permeability of vesicles can be
      tuned by introducing various amounts of silicone precursor into the liposome
      bilayer, as confirmed in calcein-release studies. The effect of fetal bovine
      serum (FBS) on the stability of liposomes was also tested in in vitro studies.
      Biological studies revealed that resulted liposomes can be considered as possible
      drug nanocarriers because they are not toxic to human skin fibroblasts (HSFs) and
      mouse embryonic fibroblasts (MEFs). 

PMID- 27022878
TI  - Whey protein concentrate doped electrospun poly(epsilon-caprolactone) fibers for
      antibiotic release improvement.
AB  - Design and fabrication of scaffolds using appropriate biomaterials are a key step
      for the creation of functionally engineered tissues and their clinical
      applications. Poly(epsilon-caprolactone) (PCL), a biodegradable and biocompatible
      material with negligible cytotoxicity, is widely used to fabricate nanofiber
      scaffolds by electrospinning for the applications of pharmaceutical products and
      wound dressings. However, the use of PCL as such in tissue engineering is limited
      due to its poor bioregulatory activity, high hydrophobicity, lack of functional
      groups and neutral charge. With the attempt to found nanofiber scaffolds with
      antibacterial activity for skin tissue engineering, in this study, whey protein
      concentrate (WPC) was used to modify the PCL nanofibers by doping it in the PCL
      electrospun solution. By adding proteins into PCL nanofibers, the degradability
      of the fibers may be increased, and this further allows an antibiotic
      incorporated in the fibers to be efficiently released. The morphology,
      wettability and degradation of the as-prepared PCL/WPC nanofibers were carefully
      characterized. The results showed that the PCL/WPC nanofibers possessed good
      morphology and wettability, as well as high degradation ability to compare with
      the pristine PCL fibers. Afterwords, tetracycline hydrochloride as a model
      antibiotic drug was doped in the PCL/WPC nanofibers. In vitro drug release assays
      demonstrated that PCL/WPC nanofibers had higher antibiotic release capability
      than the PCL nanofibers. Also, antibacterial activity evaluation against various
      bacteria showed that the drug-doped PCL/WPC fibers possessed more efficient
      antibacterial activity than the PCL nanofibers. 

PMID- 27022881
TI  - International Public Health Patients' Rights v the Protection of Patents
      Beigbeder Yves International Public Health Patients' Rights v the Protection of
      Patents 173pp Ashgate Publishing 9780754636212 0754636216.
AB  - This is an interesting insight into the workings of inter-governmental, non
      governmental and commercial organisations in health care. The author discusses
      the major health issues of developing countries, including the problems of
      providing drug therapy. Beigbeder examines the relationship between the United
      Nations, the World Health Organization, big businesses, the pharmaceutical
      industry and international public health policy in relation to breast feeding,
      essential drugs and the worldwide HIV/AIDS epidemic. This book is a must for
      those hoping to work in an international setting or with refugees. Sadly, the
      price may mean that it remains a library book.

PMID- 27022879
TI  - ALD mediated heparin grafting on nitinol for self-expanded carotid stents.
AB  - Carotid-artery atherosclerosis is a common cause of ischemic stroke. Carotid
      artery stenting (CAS) is one of the most effective treatments. However, In-stent
      restenosis (ISR) and re-endothelialization delay are two major issues of
      intravascular stent which affect clinical safety and reduce effects. In this
      study, atomic layer deposition (ALD) technology was applied to deposit a layer
      (10nm) of Al2O3 on Nitinol surface as an intermediate functional layer. The
      alumina covered surface was then modified with a coupling agent 3
      aminopropyltriethoxysilane (APS) and heparin sequentially in order to improve the
      hemocompatibility of Nitinol stents. The successful graft of APS and heparin onto
      Nitinol was proven by X-ray photoelectron spectroscopy. Furthermore, the
      predicted improvement in the biocompatibilities of modified Nitinol was confirmed
      by water contact angle measurement, protein adsorption, platelet adhesion, and
      plasma recalcification time determination. The results of hemolysis assay, cell
      proliferation and cytotoxicity tests revealed that the grafting of heparin on
      NiTi kept the original positive performance of nitinol material. The results
      indicate that ALD technology is of great potential for the manufacture of medical
      devices, especially for surface modifications and functionalization. ALD
      technology can help with modifications of inert metallic surfaces and therefore
      benefit implantable medical devices, especially intravascular stents. 

PMID- 27022882
TI  - Ischemic Postconditioning After Routine Thrombus Aspiration During Primary
      Percutaneous Coronary Intervention: Rationale and Design of the POstconditioning
      Rotterdam Trial.
AB  - BACKGROUND: Whether ischemic postconditioning (IPOC) immediately after routine
      thrombus aspiration (TA) reduces infarct size (IS) in patients with ST-segment
      elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (PPCI) has not been established. STUDY DESIGN: The POstconditioning
      Rotterdam Trial (PORT) is a dual-center, prospective, open-label, randomized
      trial with blinded endpoint evaluation enrolling 72 subjects with first-time
      STEMI, and an occluded infarct-related artery (IRA) without collaterals
      undergoing PPCI. Subjects are randomized 1:1 to a strategy of IPOC immediately
      after TA followed by stenting of the IRA or to conventional percutaneous coronary
      intervention (PCI), including TA followed by stenting of the IRA (controls).
      Cardiac magnetic resonance imaging (MRI) is performed at 3-5 days after STEMI and
      at 3 months. The primary endpoint is IS at 3 months measured by delayed
      enhancement MRI. Other secondary endpoints include MRI-derived microvascular
      obstruction (MVO), left ventricular ejection fraction, myocardial salvage index,
      enzymatic IS, ST-segment resolution, myocardial blush grade, microcirculatory
      resistance, inflammation markers, and clinical events through 3-month follow-up.
      CONCLUSIONS: PORT is testing the hypothesis that adding IPOC (against lethal
      reperfusion injury) to TA (against distal embolization and MVO) is
      cardioprotective and reduces ultimate IS in STEMI patients undergoing PPCI (Dutch
      Trial Register identifier: NTR4040). (c) 2015 Wiley Periodicals, Inc.

PMID- 27022883
TI  - Simultaneous Two-photon in Vivo Imaging of Synaptic Inputs and Postsynaptic
      Targets in the Mouse Retrosplenial Cortex.
AB  - This video shows the craniotomy procedure that allows chronic imaging of neurons
      in the mouse retrosplenial cortex (RSC) using in vivo two-photon microscopy in
      Thy1-GFP transgenic mouse line. This approach creates a possibility to
      investigate the correlation of behavioural manipulations with changes in neuronal
      morphology in vivo. The cranial window implantation procedure was considered to
      be limited only to the easily accessible cortex regions such as the barrel field.
      Our approach allows visualization of neurons in the highly vascularized RSC. RSC
      is an important element of the brain circuit responsible for spatial memory,
      previously deemed to be problematic for in vivo two-photon imaging. The cranial
      window implantation over the RSC is combined with an injection of mCherry
      expressing recombinant adeno-associated virus (rAAV(mCherry)) into the dorsal
      hippocampus. The expressed mCherry spreads out to axonal projections from the
      hippocampus to RSC, enabling the visualization of changes in both presynaptic
      axonal boutons and postsynaptic dendritic spines in the cortex. This technique
      allows long-term monitoring of experience-dependent structural plasticity in RSC.

PMID- 27022884
TI  - Persistence of energy-dependent localization in the Anderson-Hubbard model with
      increasing system size and doping.
AB  - Non-interacting systems with bounded disorder have been shown to exhibit sharp
      density of state peaks at the band edge which coincide with an energy range of
      abruptly suppressed localization. Recent work has shown that these features also
      occur in the presence of on-site interactions in ensembles of two-site Anderson
      Hubbard systems at half filling. Here we demonstrate that this effect in
      interacting systems persists away from half filling, and moreover that energy
      regions with suppressed localization continue to appear in ensembles of larger
      systems despite a loss of sharp features in the density of states. 

PMID- 27022885
TI  - Role of insulin in the pathogenesis of diabetic ketoacidosis.

PMID- 27022886
TI  - Systematic development of optimized SNEDDS of artemether with improved
      biopharmaceutical and antimalarial potential.
AB  - The current studies entail systematic development of self-nanoemulsifying drug
      delivery systems (SNEDDS) containing medium-chain triglycerides (MCTs) and long
      chain triglycerides (LCTs) for augmenting the biopharmaceutical performance of
      artemether. Equilibrium solubility and pseudoternary phase diagram studies
      facilitated selection of Captex 355 and Ethyl oleate as MCTs and LCTs, and
      Cremophor RH 40 and Tween 80 as surfactants, while Transcutol HP as cosolvent for
      formulating the SNEDDS. Systematic optimization was performed employing the Box
      Behnken design taking concentrations of lipid, surfactant and cosolvent as the
      critical material attributes (CMAs), while evaluating for globule size,
      emulsification time, dissolution efficiency and permeation as the critical
      quality attributes (CQAs). In situ single pass intestinal perfusion (SPIP)
      studies in Wistar rats substantiated significant augmentation in the absorption
      (5- to 6-fold) and permeation (4- to 5-fold) parameters from the optimized MCT
      and LCT-SNEDDS vis-a-vis the pure drug. In vivo pharmacodynamic studies in
      Plasmodium berghi infected laca mice exhibited superior reduction in the levels
      of percent parasitemia, SGOT, SGPT and bilirubin, followed by higher survival
      rate of the animals by optimized MCT-SNEDDS followed by LCT-SNEDDS vis-a-vis the
      pure drug, which was subsequently ratified through histopathological examination
      of liver tissues. Overall, the studies construed successful development of the
      optimized SNEDDS of artemether with distinctly improved biopharmaceutical and
      antimalarial potential.

PMID- 27022887
TI  - The preventive effect of fish oil on abdominal aortic aneurysm development.
AB  - Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation
      of the abdominal aorta and high rupture-related mortality rates. AAA is
      histologically characterized by oxidative stress, chronic inflammation, and
      extracellular matrix degradation in the vascular wall. We previously demonstrated
      that aortic hypoperfusion could cause the vascular inflammation and AAA
      formation. However, the preventive method for hypoperfusion-induced AAA remains
      unknown. In this study, we evaluated the effect of fish oil on AAA development
      using a hypoperfusion-induced AAA animal model. Dilation of the abdominal aorta
      in the fish oil administration group was smaller than in the control group.
      Collagen destruction and oxidative stress were suppressed in the fish oil
      administration group than in the control group. These results suggested that fish
      oil could prevent the development of AAA induced by hypoperfusion. 

PMID- 27022888
TI  - Melatonin for women in pregnancy for neuroprotection of the fetus.
AB  - BACKGROUND: Melatonin is an antioxidant with anti-inflammatory and anti-apoptotic
      effects. Animal studies have supported a fetal neuroprotective role for melatonin
      when administered maternally. It is important to assess whether melatonin, given
      to the mother, can reduce the risk of neurosensory disabilities (including
      cerebral palsy) and death, associated with fetal brain injury, for the preterm or
      term compromised fetus. OBJECTIVES: To assess the effects of melatonin when used
      for neuroprotection of the fetus. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (31 January 2016). SELECTION
      CRITERIA: We planned to include randomised controlled trials and quasi-randomised
      controlled trials comparing melatonin given to women in pregnancy (regardless of
      the route, timing, dose and duration of administration) for fetal neuroprotection
      with placebo, no treatment, or with an alternative agent aimed at providing fetal
      neuroprotection. We also planned to include comparisons of different regimens for
      administration of melatonin. DATA COLLECTION AND ANALYSIS: Two review authors
      planned to independently assess trial eligibility, trial quality and extract the
      data. MAIN RESULTS: We found no randomised trials for inclusion in this review.
      One study is ongoing. AUTHORS' CONCLUSIONS: As we did not identify any randomised
      trials for inclusion in this review, we are unable to comment on implications for
      practice at this stage.Although evidence from animals studies has supported a
      fetal neuroprotective role for melatonin when administered to the mother during
      pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant
      women have been completed to date. However, there is currently one ongoing
      randomised controlled trial (with an estimated enrolment target of 60 pregnant
      women) which examines the dose of melatonin, administered to women at risk of
      imminent very preterm birth (less than 28 weeks' gestation) required to reduce
      brain damage in the white matter of the babies that were born very
      preterm.Further high-quality research is needed and research efforts should
      directed towards trials comparing melatonin with either no intervention (no
      treatment or placebo), or with alternative agents aimed at providing fetal
      neuroprotection (such as magnesium sulphate for the very preterm infant). Such
      trials should evaluate maternal and infant short- and longer-term outcomes
      (including neurosensory disabilities such as cerebral palsy), and consider the
      costs of care.

PMID- 27022889
TI  - Exposure to Traffic-Related Air Pollution in Relation to Progression in Physical
      Disability among Older Adults.
AB  - BACKGROUND: Physical disability is common though not inevitable in older age and
      has direct bearing on a person's ability to perform activities essential for self
      care and independent living. Air pollution appears to increase the risk of
      several chronic diseases that contribute to the progression of disability.
      OBJECTIVE: We evaluated long-term exposure to traffic-related air pollution
      (TRAP) in relation to progression in physical disability. METHODS: We conducted
      our investigation within the Chicago Health and Aging Project. We measured
      participants' exposures to TRAP using two surrogates: residential proximity to
      major roads (1993 onwards) and ambient concentrations of oxides of nitrogen (NOX;
      1999 onwards), predicted via a geographic information systems-based
      spatiotemporal smoothing model (cross-validation R2 = 0.87) that incorporated
      community-based monitoring and resolved intraurban exposure gradients at a
      spatial scale of tens of meters. Participants' lower-extremity physical ability
      was assessed every 3 years (1993-2012) via tandem stand, chair stand, and timed
      walking speed. RESULTS: In multivariable-adjusted analyses (n = 5,708), higher
      long-term NOX exposure was associated with significantly faster progression in
      disability. Compared with the 5-year decline in physical ability score among
      participants in the lowest quartile of NOX exposure, decline among those in the
      highest exposure quartile was 1.14 units greater (95% confidence interval [CI]: 
      1.86, -0.42), equivalent to 3 additional years of decline among those in the
      lowest exposure quartile. The association was linear across the continuum of NOX
      exposure: per 10-ppb increment in exposure, the 5-year decline in physical
      ability score was 0.87 unit greater (95% CI: -1.35, -0.39). Proximity to a major
      road was not associated with disability progression (n = 9,994). CONCLUSIONS:
      These data join a growing body of evidence suggesting that TRAP exposures may
      accelerate aging-related declines in health. CITATION: Weuve J, Kaufman JD,
      Szpiro AA, Curl C, Puett RC, Beck T, Evans DA, Mendes de Leon CF. 2016. Exposure
      to traffic-related air pollution in relation to progression in physical
      disability among older adults. Environ Health Perspect 124:1000-1008;
      http://dx.doi.org/10.1289/ehp.1510089.

PMID- 27022890
TI  - Renal dysfunction and chronic mechanical circulatory support: from patient
      selection to long-term management and prognosis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the effects of
      mechanical circulatory support (MCS) on changes in kidney function and their
      relationship with mortality, with an additional focus on the evaluation and
      management of both preimplant and post-MCS renal dysfunction. RECENT FINDINGS:
      Renal dysfunction is highly prevalent in patients referred for MCS and is
      associated with significantly increased mortality and postoperative acute kidney
      injury. Most patients, including those with renal dysfunction, experience marked
      early improvement in renal function with MCS, likely secondary to correction of
      the cardiogenic shock, volume overload, and neurohormonal activation
      characteristic of advanced heart failure. Currently, there are no diagnostic
      tests to definitively distinguish reversible forms of renal dysfunction likely to
      improve with MCS from irreversible renal dysfunction. Furthermore, the
      characteristic improvements in renal function observed in the early months of MCS
      are often transient, with subsequent recurrence of renal dysfunction with longer
      durations of support. Venous congestion, right ventricular dysfunction, and
      reduced pulsatility are potential mechanisms involved in resurgence of renal
      dysfunction following MCS. SUMMARY: With the exponential growth of MCS, research
      endeavors to both improve understanding of the mechanisms behind observed changes
      in renal function and elucidate the device-related effects on the kidney are
      imperative.

PMID- 27022891
TI  - Human-induced pluripotent stem cell approaches to model inborn and acquired
      metabolic heart diseases.
AB  - PURPOSE OF REVIEW: The article provides an overview of advances in the induced
      pluripotent stem cell field to model cardiomyopathies of inherited inborn errors
      of metabolism and acquired metabolic syndromes in vitro. RECENT FINDINGS: Several
      inborn errors of metabolism have been studied using 'disease in a dish' models,
      including Pompe disease, Danon disease, Fabry disease, and Barth syndrome.
      Disease phenotypes of complex metabolic syndromes, such as diabetes mellitus and
      aldehyde dehydrogenase 2 deficiency, have also been observed. SUMMARY:
      Differentiation of patient and disease-specific induced pluripotent stem cell
      derived cardiomyocytes has provided the capacity to model deleterious
      cardiometabolic diseases to understand molecular mechanisms, perform drug
      screens, and identify novel drug targets.

PMID- 27022892
TI  - The future of mechanical circulatory support for advanced heart failure.
AB  - PURPOSE OF REVIEW: Mechanical circulatory support (MCS) has become the main focus
      of heart replacement therapy for end stage heart failure patients. Advances in
      technology are moving towards miniaturization, biventricular support devices,
      complete internalization, improved hemocompatibility profiles, and responsiveness
      to cardiac loading conditions. This review will discuss the recent advances and
      investigational devices in MCS for advanced heart failure. RECENT FINDINGS: The
      demand for both short-term and long-term durable devices for advanced heart
      failure is increasing. The current devices are still fraught with an unacceptably
      high incidence of gastrointestinal bleeding and thromboembolic and infectious
      complications. New devices are on the horizon focusing on miniaturization,
      versatility for biventricular support, improved hemocompatibility, use of
      alternate energy sources, and incorporation of continuous hemodynamic monitoring.
      SUMMARY: The role for MCS in advanced heart replacement therapy is steadily
      increasing. With the advent of newer generation devices on the horizon, the
      potential exists for MCS to surpass heart transplantation as the primary therapy
      for advanced heart failure.

PMID- 27022894
TI  - Advances in mechanical circulatory support.

PMID- 27022895
TI  - Rupture of esophagus by compressed air.
AB  - Currently, beverages containing compressed air such as cola and champagne are
      widely used in our daily life. Improper ways to unscrew the bottle, usually by
      teeth, could lead to an injury, even a rupture of the esophagus. This letter to
      editor describes a case of esophageal rupture caused by compressed air.

PMID- 27022898
TI  - Peer coaching for all.

PMID- 27022896
TI  - Comparison of Outcomes with Arteriovenous Fistula and Arteriovenous Graft for
      Vascular Access in Hemodialysis: A Prospective Cohort Study.
AB  - BACKGROUND: Poor vessel quality and limited life expectancy in the elderly may
      make arteriovenous fistula (AVF) less ideal than arteriovenous graft (AVG) or
      catheter for vascular access (VA) in hemodialysis (HD). METHODS: A total of 946
      adult incident HD patients from clinical research center registry for end-stage
      renal disease prospective cohort in South Korea were analyzed for outcomes with
      AVF and AVG. RESULTS: Overall, AVF was associated with better patient survival
      only in male (p < 0.001) and diabetic (p = 0.004) patients, although it was
      superior to AVG in access patency, regardless of diabetes mellitus status and
      gender. AVG (vs. AVF; hazard ratio (HR) 2.282; 95% CI 1.071-4.861; p = 0.032) was
      associated with poor patient survival. In elderly patients (>=65 years), AVF was
      associated with survival benefit only in male (p < 0.001) and diabetic (p = 0.04)
      patients, and with better access patency only in female (p = 0.05) and diabetic
      (p = 0.04) patients. AVG (vs. AVF; HR 3.158; 95% CI 1.080-9.238; p = 0.036) was
      associated with poor patient survival. In septuagenarian patients, AVF was
      associated only with survival benefit (p = 0.01) and there was no advantage in
      access patency (p = 0.12). However, AVF was superior to AVG in both access
      patency (p = 0.001) and patient survival (p = 0.03) even with propensity
      matching. CONCLUSION: AVF is the more desirable VA and its survival benefits
      warrant its consideration in septuagenarian patients although a prolonged life
      expectancy is essential to realize the potential benefits of AVF.

PMID- 27022899
TI  - Richard Hader Visionary Leader Award.

PMID- 27022893
TI  - Epigenetic regulation in heart failure.
AB  - PURPOSE OF REVIEW: This article provides an overview, highlighting recent
      findings, of a major mechanism of gene regulation and its relevance to the
      pathophysiology of heart failure. RECENT FINDINGS: The syndrome of heart failure
      is a complex and highly prevalent condition, one in which the heart undergoes
      substantial structural remodeling. Triggered by a wide range of disease-related
      cues, heart failure pathophysiology is governed by both genetic and epigenetic
      events. Epigenetic mechanisms, such as chromatin/DNA modifications and noncoding
      RNAs, have emerged as molecular transducers of environmental stimuli to control
      gene expression. Here, we emphasize metabolic milieu, aging, and hemodynamic
      stress as they impact the epigenetic landscape of the myocardium. SUMMARY: Recent
      studies in multiple fields, including cancer, stem cells, development, and
      cardiovascular biology, have uncovered biochemical ties linking epigenetic
      machinery and cellular energetics and mitochondrial function. Elucidation of
      these connections will afford molecular insights into long-established
      epidemiological observations. With time, exploitation of the epigenetic machinery
      therapeutically may emerge with clinical relevance.

PMID- 27022900
TI  - Sharing supervision and liability as a nurse manager.

PMID- 27022901
TI  - Pulling together: Team-based performance sharing.

PMID- 27022902
TI  - Building a better research nurse coordinator orientation program.

PMID- 27022903
TI  - The impact of genomics on health outcomes, quality, and safety.

PMID- 27022904
TI  - Care coordination in rural areas.

PMID- 27022905
TI  - Rethinking rituals.

PMID- 27022906
TI  - Bringing clarity to job shadowing.

PMID- 27022907
TI  - Dress for respect: A shared governance approach.

PMID- 27022908
TI  - Leadership Q&A.

PMID- 27022909
TI  - Most and Least Preferred Colours Differ According to Object Context: New Insights
      from an Unrestricted Colour Range.
AB  - Humans like some colours and dislike others, but which particular colours and why
      remains to be understood. Empirical studies on colour preferences generally
      targeted most preferred colours, but rarely least preferred (disliked) colours.
      In addition, findings are often based on general colour preferences leaving open
      the question whether results generalise to specific objects. Here, 88
      participants selected the colours they preferred most and least for three context
      conditions (general, interior walls, t-shirt) using a high-precision colour
      picker. Participants also indicated whether they associated their colour choice
      to a valenced object or concept. The chosen colours varied widely between
      individuals and contexts and so did the reasons for their choices. Consistent
      patterns also emerged, as most preferred colours in general were more chromatic,
      while for walls they were lighter and for t-shirts they were darker and less
      chromatic compared to least preferred colours. This meant that general colour
      preferences could not explain object specific colour preferences. Measures of the
      selection process further revealed that, compared to most preferred colours,
      least preferred colours were chosen more quickly and were less often linked to
      valenced objects or concepts. The high intra- and inter-individual variability in
      this and previous reports furthers our understanding that colour preferences are
      determined by subjective experiences and that most and least preferred colours
      are not processed equally. 

PMID- 27022910
TI  - Role of Livelihood Capital in Reducing Climatic Vulnerability: Insights of
      Australian Wheat from 1990-2010.
AB  - In many agricultural countries, development of rural livelihood through
      increasing capital is a major regional policy to adapt to climate change.
      However, the role of livelihood capital in reducing climatic vulnerability is
      uncertain. This study assesses vulnerability and identifies the effects of common
      capital indicators on it, using Australian wheat as an example. We calculate
      exposure (a climate index) and sensitivity (a wheat failure index) to measure
      vulnerability and classify the resilient and sensitive cases, and express
      adaptive capacity through financial, human, natural, physical, and social capital
      indicators for 12 regions in the Australian wheat-sheep production zone from 1991
      2010. We identify relationships between 12 indicators of five types of capital
      and vulnerability with t-tests and six logistic models considering the capital
      indicator itself, its first-order lag and its square as dependent variables to
      test the hypothesis that a high level of each capital metric results in low
      vulnerability. Through differing adaptive capacities between resilient and
      sensitive groups, we found that only four of the 12 (e.g., the access to finance,
      cash income level, total crop gross revenues, and family share of farm income)
      relate to vulnerability, which challenges the hypothesis that increasing capital
      reduces vulnerability. We conclude that further empirical reexaminations are
      required to test the relationships between capital measures and vulnerability
      under the sustainable livelihood framework (SLF). 

PMID- 27022911
TI  - New therapies for psoriasis and psoriatic arthritis.
AB  - PURPOSE OF REVIEW: Over the last several years, novel immunologic pathways
      pivotal in the development of the pathobiology of psoriasis and psoriatic
      arthritis (PsA) have been revealed. These discoveries catalyzed a search for new
      treatment targets resulting in many new therapies that are now available for
      patients with psoriatic disease. RECENT FINDINGS: Helper T cells that secrete
      interleukin-17 (TH17) along with CD8+ cells, innate lymphocyte cells, and gamma
      delta T cells are important in the pathogenesis of psoriasis and PsA. Recently,
      agents that target interleukin-17, the interleukin-17 receptor, and interleukin
      23 (antip19) have been approved or are in clinical trials. Apremilast, a new oral
      agent, was approved for the treatment of psoriasis and PsA. SUMMARY: Secukinumab,
      an interleukin-17A antibody, has been approved for treatment of psoriasis and PsA
      in the United States. It is effective with a good safety profile. Ixekizumab,
      another anti-interleukin-17A antibody, is currently in clinical trials and
      brodalumab, an interleukin-17 receptor antagonist, was removed from clinical
      trials because of safety concerns despite demonstrated efficacy in psoriasis and
      PsA. Targeting interleukin-23 with antibodies to p19 is another approach with
      encouraging results in psoriasis. Apremilast, an oral agent, approved to treat
      psoriasis and PsA demonstrates moderate efficacy with an excellent safety record.
      The role of tofacitinib in psoriatic disease remains to be determined pending a
      safety review in psoriasis and completion of PsA trials.

PMID- 27022912
TI  - Essure microinsert imaging: does abnormal shape on ultrasound predict
      complications on HSG?
AB  - OBJECTIVE: We hypothesize that the shape of the Essure microinsert on ultrasound
      is able to predict complications evident on hysterosalpingogram (HSG), the
      accepted gold standard. METHOD AND MATERIALS: From July 2, 2009 to July 2, 2012,
      441 women at our institution received Essure microinsert placement for the
      purpose of permanent sterilization. 2D and 3D coronal plane transvaginal
      ultrasounds were performed three months after Essure microinsert placement. Those
      patients with complications identified on ultrasound, a non-diagnostic
      ultrasound, or following a difficult insertion were referred for HSG. Patients
      with both HSG and ultrasound performed were retrospectively selected and
      anonymized. The ultrasounds were reviewed by a single, blinded radiologist. A
      total of 122 microinserts in 65 patients were described on ultrasound using a
      numeric grading system and compared to HSG findings. RESULTS: Microinsert
      placement resulted in 37 complications, 31 of which were identified on
      ultrasound, including uterine and tubal perforations and placement in the
      endometrial cavity. The sensitivity of Essure microinsert shape on ultrasound in
      predicting complications, compared with standard HSG, was 94%, with a positive
      predictive value of 85%; specificity was 95%, with a negative predictive value of
      98%. The Kappa coefficient was 0.85 (p < 0.001). CONCLUSION: Our results suggest
      that ultrasound may be used as a frontline imaging modality for patients after
      Essure microinsert placement.

PMID- 27022913
TI  - A Randomized Controlled Trial of Two Different Macronutrient Profiles on Weight,
      Body Composition and Metabolic Parameters in Obese Adolescents Seeking Weight
      Loss.
AB  - OBJECTIVE: Adolescent obesity is difficult to treat and the optimal dietary
      pattern, particularly in relation to macronutrient composition, remains
      controversial. This study tested the effect of two structured diets with
      differing macronutrient composition versus control, on weight, body composition
      and metabolic parameters in obese adolescents. DESIGN: A randomized controlled
      trial conducted in a children's hospital. METHODS: Eighty seven obese youth
      (means: age 13.6 years, BMI z-score 2.2, waist: height ratio 0.65, 69% female)
      completed a psychological preparedness program and were then randomized to a
      short term 'structured modified carbohydrate' (SMC, 35% carbohydrate; 30%
      protein; 35% fat, n = 37) or a 'structured low fat' (SLF, 55% carbohydrate; 20%
      protein; 25% fat, n = 36) or a wait listed control group (n = 14).
      Anthropometric, body composition and biochemical parameters were measured at
      randomization and after 12 weeks, and analyzed under the intention to treat
      principle using analysis of variance models. RESULTS: After 12 weeks, data was
      collected from 79 (91%) participants. BMI z-scores were significantly lower in
      both intervention groups compared to control after adjusting for baseline values,
      SLF vs. control, mean difference = -0.13 (95%CI = -0.18, -0.07), P<0.001; SMC vs.
      control, -0.14 (-0.19, -0.09), P<0.001, but there was no difference between the
      two intervention diet groups: SLF vs. SMC, 0.00 (-0.05, 0.04), P = 0.83.
      CONCLUSIONS: Both dietary patterns resulted in similar changes in weight, body
      composition and metabolic improvements compared to control. The use of a
      structured eating system which allows flexibility but limited choices can assist
      in weight change and the rigid application of a low fat eating pattern is not
      exclusive in its efficacy. TRIAL REGISTRATION: International Clinical Trials
      Registry ISRCTN49438757.

PMID- 27022914
TI  - Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator
      Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth
      Factor beta1 in Patients Undergoing Hemodialysis.
AB  - BACKGROUND: There is substantial evidence that chronic renal and cardiovascular
      diseases are associated with coagulation disorders, endothelial dysfunction,
      inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion
      polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular
      diseases. Therefore, this study aimed to compare plasma levels of ultrassensible
      C-reactive protein (usCRP), PAI-1, D-dimer and TGF-beta1 in patients undergoing
      HD with different ACE I/D polymorphisms. METHODS: The study was performed in 138
      patients at ESRD under hemodialysis therapy for more than six months. The
      patients were divided into three groups according to the genotype. Genomic DNA
      was extracted from blood cells (leukocytes). ACE I/D polymorphism was
      investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer,
      PAI-1 and TGF-beta1 were measured by enzyme-linked immunosorbent assay (ELISA),
      and the determination of plasma levels of usCRP was performed by
      immunonephelometry. Data were analyzed by the software SigmaStat 2.03. RESULTS:
      Clinical characteristics were similar in patients with these three ACE I/D
      polymorphisms, except for interdialytic weight gain. I allele could be associated
      with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and
      as ID had significantly higher levels of PAI-1 than those with II genotype. Other
      laboratory parameters did not significantly differ among the three subgroups (P =
      0.033). Despite not reaching statistical significance, plasma levels of usCRP
      were higher in patients carrying the D allele. CONCLUSION: ACE I/D polymorphisms
      could be associated with changes in the regulation of sodium, fibrinolytic
      system, and possibly, inflammation. Our data showed that high levels of PAI-1 are
      detected when D allele is present, whereas greater interdialytic gain is
      associated with the presence of I allele. However, further studies with different
      experimental designs are necessary to elucidate the mechanisms involved in these
      associations.

PMID- 27022915
TI  - Neurocognitive functioning in patients with glioma of the left and right temporal
      lobes.
AB  - Patients with glioma frequently suffer from deficits of neurocognitive
      functioning (NCF), though few studies have assessed NCF in localized glioma
      patients prior to surgery. One hundred and three patients (M age = 52.0; M
      education = 14.6 years) with histologically confirmed glioma in the right (RTL: n
      = 30; 57 % glioblastoma) or left temporal lobe (LTL: n = 73; 49 % glioblastoma)
      completed presurgical neuropsychological assessment. Impairment of NCF was
      identified in 75 % of all patients. Notably, patients with RTL glioma were most
      frequently impaired on measures of verbal memory and executive functioning, and
      at similar rates as the LTL group. Nonetheless, chi(2) tests revealed that
      impairment rates were significantly higher in the LTL group on attention and
      object naming tests (p <= .05). Independent-samples t-tests revealed that mean
      performances of patients with LTL glioma were also significantly below RTL
      patients on measures of attention (p = .01), verbal learning and memory (p =
      .05), and language (p < .03). A trend was observed in which anterior LTL tumors
      were associated with reduced verbal learning and medial LTL lesions with delayed
      recall problems, though patients with lesions involving multiple LTL regions
      exhibited the greatest difficulty across all verbal memory measures. Significant
      group differences in NCF performances remained so after controlling for FLAIR
      volume and tumor histology. These findings indicate that temporal lobe glioma
      frequently present with impaired NCF, though impairments are often milder in RTL
      compared to LTL patients. Nonetheless, the relatively frequent verbal memory
      impairment in the RTL group underscores the bilaterality of verbal memory
      processes.

PMID- 27022916
TI  - The Influence of Plant Litter on Soil Water Repellency: Insight from 13C NMR
      Spectroscopy.
AB  - Soil water repellency (SWR, i.e. reduced affinity for water owing to the presence
      of organic hydrophobic coatings on soil particles) has relevant hydrological
      implications because low rates of infiltration enhance water runoff, and
      untargeted diffusion of fertilizers and pesticides. Previous studies investigated
      the occurrence of SWR in ecosystems with different vegetation cover but did not
      clarify its relationships with litter biochemical quality. Here, we investigated
      the capability of different plant litter types to induce SWR by using fresh and
      decomposed leaf materials from 12 species, to amend a model sandy soil over a
      year-long microcosm experiment. Water repellency, measured by the Molarity of an
      Ethanol Droplet (MED) test, was tested for the effects of litter species and age,
      and compared with litter quality assessed by 13C-CPMAS NMR in solid state and
      elemental chemical parameters. All litter types were highly water repellent, with
      MED values of 18% or higher. In contrast, when litter was incorporated into the
      soil, only undecomposed materials induced SWR, but with a large variability of
      onset and peak dynamics among litter types. Surprisingly, SWR induced by litter
      addition was unrelated to the aliphatic fraction of litter. In contrast, lignin
      poor but labile C-rich litter, as defined by O-alkyl C and N-alkyl and methoxyl C
      of 13C-CPMAS NMR spectral regions, respectively, induced a stronger SWR. This
      study suggests that biochemical quality of plant litter is a major controlling
      factor of SWR and, by defining litter quality with 13C-CPMAS NMR, our results
      provide a significant novel contribution towards a full understanding of the
      relationships between plant litter biochemistry and SWR. 

PMID- 27022917
TI  - Factors Influencing Non-Persistence with Antiplatelet Medications in Elderly
      Patients After Ischaemic Stroke.
AB  - OBJECTIVES: This study investigated the extent of, and patient-related
      characteristics for, non-persistence with antiplatelet therapy during follow-up
      in elderly patients after their first ischaemic non-cardioembolic stroke.
      METHODS: A database of the largest health insurance provider in the Slovak
      Republic was used to assemble the study cohort of 4319 patients (56.8% were
      women) aged >=65 years in whom antiplatelet therapy was initiated following a
      hospital-based diagnosis of stroke during the period 1 January 2010 to 31
      December 2010. Patients were followed for 3 years from the date on which the
      first prescription of antiplatelet medication was recorded. Patients with a 6
      month treatment gap without antiplatelet medication prescription were designated
      as non-persistent, and the Cox proportional hazards model was used to identify
      predictors of non-persistence. RESULTS: At the end of the 3-year follow-up
      period, 1184 (27.4%) patients were considered non-persistent with antiplatelet
      medication. In 1244 (28.8%) patients, a switch in the use of a particular
      antiplatelet drug was registered during this follow-up period. Female sex (hazard
      ratio [HR] 1.25) was associated with increased risk of non-persistence. In
      contrast, factors associated with lower probability of non-persistence were age
      >=75 years (HR 0.72), switch in antiplatelet medication use (HR 0.76), diabetes
      mellitus (HR 0.81), dementia (HR 0.69) and epilepsy (HR 0.69). CONCLUSIONS: Our
      results suggest that women, patients aged <75 years, and patients without certain
      comorbid conditions may need improved assistance in secondary prevention
      management after an ischaemic stroke.

PMID- 27022918
TI  - Gender Differentiated Preferences for a Community-Based Conservation Initiative.
AB  - Community-based conservation (CBC) aims to benefit local people as well as to
      achieve conservation goals, but has been criticised for taking a simplistic view
      of "community" and failing to recognise differences in the preferences and
      motivations of community members. We explore this heterogeneity in the context of
      Kenya's conservancies, focussing on the livelihood preferences of men and women
      living adjacent to the Maasai Mara National Reserve. Using a discrete choice
      experiment we quantify the preferences of local community members for key
      components of their livelihoods and conservancy design, differentiating between
      men and women and existing conservancy members and non-members. While Maasai
      preference for pastoralism remains strong, non-livestock-based livelihood
      activities are also highly valued and there was substantial differentiation in
      preferences between individuals. Involvement with conservancies was generally
      perceived to be positive, but only if households were able to retain some land
      for other purposes. Women placed greater value on conservancy membership, but
      substantially less value on wage income, while existing conservancy members
      valued both conservancy membership and livestock more highly than did non
      members. Our findings suggest that conservancies can make a positive contribution
      to livelihoods, but care must be taken to ensure that they do not unintentionally
      disadvantage any groups. We argue that conservation should pay greater attention
      to individual-level differences in preferences when designing interventions in
      order to achieve fairer and more sustainable outcomes for members of local
      communities. 

PMID- 27022920
TI  - Optical Coherence Tomography Angiography of Idiopathic Polypoidal Choroidal
      Vasculopathy.
AB  - PURPOSE: To analyze the morphological characteristics of polypoidal choroidal
      vasculopathy (PCV) on optical coherence tomography angiography (OCT-A). METHODS:
      Consecutive patients with PCV underwent complete ophthalmological examination,
      including fundus photography, fluorescein angiography, indocyanine green
      angiography, spectral-domain OCT and OCT-A. RESULTS: Segmentation of the
      choriocapillaris layer on OCT-A revealed the branching vascular network as a
      hyper-flow lesion, and it revealed the polypoidal lesion as a hyper-flow round
      structure surrounded by a hypo-intense halo in some cases and as a hypo-flow
      round structure in most cases. CONCLUSION: OCT-A is a noninvasive imaging
      modality that allows for the visualization of different structures in PCV. The
      branching vascular network is consistently and clearly detected. The hypo-flow
      round appearance of the polyps on OCT-A is probably due to unusual blood flow
      inside of the polypoidal lesions, in contrast with the branching vascular
      network. Further improvements in OCT-A knowledge will provide information on the
      specificity of the different intensity characteristics in PCV.

PMID- 27022921
TI  - Heidelberg Spectralis Optical Coherence Tomography Angiography: Technical
      Aspects.
AB  - Optical coherence tomography angiography (OCT-A) is a promising new method for
      visualizing the retinal vasculature and choroidal vascular layers in the macular
      area and provides depth-resolved functional information on blood flow in these
      vessels. OCT-A is based on the concept that in a static eye the only moving
      structure in the fundus of the eye is blood flowing through the vessels. Contrast
      is generated based on the difference between moving cells in the vasculature and
      the static surrounding tissue. Artifacts can arise due to scan positioning errors
      caused by normal ocular microsaccades. In order to avoid artifacts, a sequence of
      OCT B-scans in the exact same retinal location must be taken to detect flow.
      Active eye-tracking (TruTrackTM) using the simultaneous acquisition of fundus and
      optical coherence tomography (OCT) images presents a very reliable method of
      acquiring OCT volume scans without motion artifacts and helps significantly
      improve signal-to-noise ratio. This system also allows the use of a full spectrum
      amplitude decorrelation algorithm that produces clear differentiation between
      blood flow and static tissue without sacrificing the axial resolution of OCT
      images. Accuracy in layer segmentation, which requires high-resolution OCT B
      scans, is crucial for producing reliable OCT-A images. This can be achieved
      through automated or manual layer segmentation. During OCT scan acquisition, the
      effect of axial motion (e.g. a patient moving towards the camera) is compensated
      for by geometric alignment of successive B-scans before analyzing temporal
      changes. 

PMID- 27022919
TI  - Unfolded protein response in pollen development and heat stress tolerance.
AB  - KEY MESSAGE: Importance of the UPR for pollen. Pollen is particularly sensitive
      to environmental conditions that disturb protein homeostasis, such as higher
      temperatures. Their survival is dependent on subcellular stress response systems,
      one of which maintains protein homeostasis in the endoplasmic reticulum (ER).
      Disturbance of ER proteostasis due to stress leads to the activation of the
      unfolded protein response (UPR) that mitigates stress damage mainly by increasing
      ER-folding capacity and reducing folding demands. The UPR is controlled by ER
      membrane-associated transcription factors and an RNA splicing factor. They are
      important components of abiotic stress responses including general heat stress
      response and thermotolerance. In addition to responding to environmental
      stresses, the UPR is implicated in developmental processes required for
      successful male gametophyte development and fertilization. Consequently, defects
      in the UPR can lead to pollen abortion and male sterility. Several UPR components
      are involved in the elaboration of the ER network, which is required for pollen
      germination and polar tube growth. Transcriptome and proteome analyses have shown
      that components of the ER-folding machinery and the UPR are upregulated at
      specific stages of pollen development supporting elevated demands for secretion.
      Furthermore, genetic studies have revealed that knockout mutants of UPR genes are
      defective in producing viable or competitive pollen. In this review, we discuss
      recent findings regarding the importance of the UPR for both pollen development
      and stress response.

PMID- 27022922
TI  - Medicine for the City: Perspective and Solidarity as Tools for Making Urban
      Health.
AB  - The United States has pursued policies of urban upheaval that have undermined
      social organization, dispersed people, particularly African Americans, and
      increased rates of disease and disorder. Healthcare institutions have been, and
      can be, a part of this problem or a part of the solution. This essay addresses
      two tools that healthcare providers can use to repair the urban ecosystem
      perspective and solidarity. Perspective addresses both our ability to envision
      solutions and our ability to see in the space in which we move. Solidarity is our
      ability to appreciate our fellowship with other people, a mindset that is at the
      heart of medical practice. These two tools lay the foundation for structurally
      competent healthcare providers to act in a restorative manner to create a health
      giving built environment. 

PMID- 27022923
TI  - Fundamental Interventions: How Clinicians Can Address the Fundamental Causes of
      Disease.
AB  - In order to enhance the "structural competency" of medicine-the capability of
      clinicians to address social and institutional determinants of their patients'
      health-physicians need a theoretical lens to see how social conditions influence
      health and how they might address them. We consider one such theoretical lens,
      fundamental cause theory, and propose how it might contribute to a more
      structurally competent medical profession. We first describe fundamental cause
      theory and how it makes the social causes of disease and health visible. We then
      outline the sorts of "fundamental interventions" that physicians might make in
      order to address the fundamental causes. 

PMID- 27022924
TI  - Preventing Torture in Nepal: A Public Health and Human Rights Intervention.
AB  - In this article we address torture in military and police organizations as a
      public health and human rights challenge that needs to be addressed through
      multiple levels of intervention. While most mental health approaches focus on
      treating the harmful effects of such violence on individuals and communities, the
      goal of the project described here was to develop a primary prevention strategy
      at the institutional level to prevent torture from occurring in the first place.
      Such an approach requires understanding and altering the conditions that cause
      and sustain "atrocity producing situations" (Lifton 2000, 2004). Given the
      persistence of torture across the world and its profound health consequences,
      this is an increasingly important issue in global health and human rights. 

PMID- 27022925
TI  - Respiratory Conditions Associated with Tracheobronchomegaly (Mounier-Kuhn
      Syndrome): A Study of Seventeen Cases.
AB  - BACKGROUND: Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by
      enlargement of the trachea and main bronchi and associated with recurrent
      respiratory tract infections. OBJECTIVE: This multicenter, retrospective study
      was carried out to describe respiratory conditions associated with
      tracheobronchomegaly. METHODS: Nine institutions involved in the 'Groupe
      d'Endoscopie de Langue Francaise' (GELF) participated in this study. A standard
      form was used to record patient characteristics, treatments and follow-up from
      medical charts. RESULTS: Seventeen patients, 53% male, aged 58 +/- 18 years at
      diagnosis were included. Recurrent infections revealed MKS in 88% of cases. Main
      comorbid conditions were diffuse bronchiectasis in 88% of patients and
      tracheobronchomalacia in 67% of cases. The exacerbation rate was 1.5
      exacerbations/patient/year. The main non-respiratory morbid condition was
      gastroesophageal reflux disease in 29% of cases. Interventional bronchoscopy was
      performed in seven patients (41%), consisting of laser (n = 2) and tracheal
      stenting (n = 5). Complications related to stents were observed in 80% of cases
      with a mean stent duration of 8 months. Four deaths, including three due to
      respiratory causes, occurred during follow-up. CONCLUSIONS: This is the largest
      series of MKS reported in the literature, showing that bronchiectasis and
      tracheobronchomalacia are the main associated morbid conditions that constitute a
      challenge for treatment.

PMID- 27022926
TI  - Increased Duration of Paid Maternity Leave Lowers Infant Mortality in Low- and
      Middle-Income Countries: A Quasi-Experimental Study.
AB  - BACKGROUND: Maternity leave reduces neonatal and infant mortality rates in high
      income countries. However, the impact of maternity leave on infant health has not
      been rigorously evaluated in low- and middle-income countries (LMICs). In this
      study, we utilized a difference-in-differences approach to evaluate whether paid
      maternity leave policies affect infant mortality in LMICs. METHODS AND FINDINGS:
      We used birth history data collected via the Demographic and Health Surveys to
      assemble a panel of approximately 300,000 live births in 20 countries from 2000
      to 2008; these observational data were merged with longitudinal information on
      the duration of paid maternity leave provided by each country. We estimated the
      effect of an increase in maternity leave in the prior year on the probability of
      infant (<1 y), neonatal (<28 d), and post-neonatal (between 28 d and 1 y after
      birth) mortality. Fixed effects for country and year were included to control
      for, respectively, unobserved time-invariant confounders that varied across
      countries and temporal trends in mortality that were shared across countries.
      Average rates of infant, neonatal, and post-neonatal mortality over the study
      period were 55.2, 30.7, and 23.0 per 1,000 live births, respectively. Each
      additional month of paid maternity was associated with 7.9 fewer infant deaths
      per 1,000 live births (95% CI 3.7, 12.0), reflecting a 13% relative reduction.
      Reductions in infant mortality associated with increases in the duration of paid
      maternity leave were concentrated in the post-neonatal period. Estimates were
      robust to adjustment for individual, household, and country-level
      characteristics, although there may be residual confounding by unmeasured time
      varying confounders, such as coincident policy changes. CONCLUSIONS: More
      generous paid maternity leave policies represent a potential instrument for
      facilitating early-life interventions and reducing infant mortality in LMICs and
      warrant further discussion in the post-2015 sustainable development agenda. From
      a policy planning perspective, further work is needed to elucidate the mechanisms
      that explain the benefits of paid maternity leave for infant mortality.

PMID- 27022927
TI  - Laparoscopic intersphincteric resection: indications and results.
AB  - Surgical treatment of distal rectal cancer has long been based only on
      abdominoperineal excision, resulting in a permanent stoma and not always offering
      a definitive local control. Sphincter saving surgery has emerged in the last 20
      years and can be offered also to patients with low lying tumours, provided that
      the external sphincter is not involved by the disease. An intersphincteric
      resection (ISR) is based on the resection of the rectum with a distal dissection
      proceeding into the space between the internal and the external anal sphincter.
      Originally described as an open procedure, it has also been developed with the
      laparoscopic approach, and also this technically demanding procedure is inscribed
      among those offered to the patient by a minimally invasive surgery. Indications
      have to be strict and patient selection is crucial to obtain both oncological and
      functional optimal results. The level of distal dissection and the extent of
      internal sphincter resected are chosen according to the distal margin of the
      tumour and is based on MRI findings: accurate imaging is therefore mandatory to
      better define the surgical approach. We here present our actual indications for
      ISR, results in terms of operative time, median hospital stay for ISR in our
      experience and review the updated literature. 

PMID- 27022928
TI  - Attentional Effects on Phenomenological Appearance: How They Change with Task
      Instructions and Measurement Methods.
AB  - It has been reported that exogenous cues accentuate contrast appearance. The
      empirical finding is controversial because non-veridical perception challenges
      the idea that attention prioritizes processing resources to make perception
      better, and because philosophers have used the finding to challenge
      representational accounts of mental experience. The present experiments confirm
      that when evaluated with comparison paradigms exogenous cues increase the
      apparent contrast. In addition, contrast appearance was also changed by simply
      changing the purpose of a secondary task. When comparison and discrimination
      reports were combined in a single experiment there was a behavioral
      disassociation: contrast enhanced for comparison responses, but did not change
      for discrimination judgments, even when participants made both types of judgment
      for a single stimulus. That a single object can have multiple simultaneous
      appearances leads inescapably to the conclusion that our unitary mental
      experience is illusory. 

PMID- 27022929
TI  - Opioid use in patients with rheumatoid arthritis 2005-2014: a population-based
      comparative study.
AB  - Opioid prescriptions have seen an increase across the USA, Canada, Europe, and
      the UK. In the USA, they have quadrupled from 1999 to 2010. Opioid use among
      patients with rheumatoid arthritis (RA) over time is not well described. This
      study examined trends of opioid use in patients with RA. Retrospective
      prescription data was examined from 2005 to 2014 in a population-based incidence
      cohort of patients with RA by 1987 ACR criteria and comparable non-RA subjects.
      Differences in opioid use were examined with Poisson models. A total of 501
      patients with RA (71 % female) and 532 non-RA subjects (70 % female) were
      included in the study. Total and chronic opioid use in 2014 was substantial in
      both cohorts 40 % RA vs 24 % non-RA and 12 % RA vs. 4 % non-RA, respectively.
      Opioid use increased by 19 % per year in both cohorts during the study period (95
      % confidence interval [CI] 1.15, 1.25). Relative risk (RR) of chronic opiate use
      for RA patients compared to non-RA subjects was highest in adults aged 50-64
      years (RR 2.82; 95 % CI 1.43-6.23). RA disease characteristics, biologic use at
      index, treated depression/fibromyalgia, education, and smoking status were not
      significantly associated with chronic opiate use. Over a third of patients with
      RA use opioids in some form, and in more than a tenth use is chronic. Use has
      increased in recent years. Patients aged 50-64 with RA use substantially more
      opioids than their non-RA counterparts. 

PMID- 27022930
TI  - The Type III Secretion Translocation Pore Senses Host Cell Contact.
AB  - Type III secretion systems (T3SS) are nano-syringes used by a wide range of Gram
      negative pathogens to promote infection by directly injecting effector proteins
      into targeted host cells. Translocation of effectors is triggered by host-cell
      contact and requires assembly of a pore in the host-cell plasma membrane, which
      consists of two translocator proteins. Our understanding of the translocation
      pore, how it is assembled in the host cell membrane and its precise role in
      effector translocation, is extremely limited. Here we use a genetic technique to
      identify protein-protein contacts between pore-forming translocator proteins, as
      well as the T3SS needle-tip, that are critical for translocon function. The data
      help establish the orientation of the translocator proteins in the host cell
      membrane. Analysis of translocon function in mutants that break these contacts
      demonstrates that an interaction between the pore-forming translocator PopD and
      the needle-tip is required for sensing host cell contact. Moreover, tethering
      PopD at a dimer interface also specifically prevents host-cell sensing, arguing
      that the translocation pore is actively involved in detecting host cell contact.
      The work presented here therefore establishes a signal transduction pathway for
      sensing host cell contact that is initiated by a conformational change in the
      translocation pore, and is subsequently transmitted to the base of the apparatus
      via a specific contact between the pore and the T3SS needle-tip. 

PMID- 27022931
TI  - Association of interleukin-10 gene promoter polymorphisms with recurrent
      pregnancy loss: a meta-analysis.
AB  - PURPOSE: It has been reported single-nucleotide polymorphisms (SNPs) of the IL-10
      promoter might be associated with the susceptibility to recurrent pregnancy loss
      (RPL). Owing to the inconclusive results, we conducted a meta-analysis to
      systematically summarize and clarify the association between the IL-10 promoter
      SNPs and RPL risk. METHODS: A systematic search of studies on the association of
      the three SNPs with RPL was conducted in PubMed and Embase. Odds ratios (ORs) and
      95 % confidence intervals (95 % CIs) were used to pool the effect size. RESULT:
      Eleven case-control studies on rs1800896, seven studies on rs1800871, and eight
      studies on rs1800872 were included. A significant association was identified
      between IL-10 rs1800896 with RPL risk (G versus A: OR = 1.21, 95 % CI 1.09-1.35).
      No evidence of association was found between rs1800871 and RPL when restricted to
      those studies in Hardy-Weinberg equilibrium in controls (T versus C: OR = 1.25,
      95 % CI 0.76-2.06). No statistical association was demonstrated between rs1800872
      and RPL (C versus A: OR = 1.08, 95 % CI 0.83-1.42). CONCLUSIONS: IL-10 rs1800896
      significantly increases the risk of RPL, while rs1800872 is not correlated with
      RPL risk. No significant association is demonstrated between rs1800871 and RPL
      risk but this requires further investigation.

PMID- 27022932
TI  - Radiotherapy for Adrenal Metastasis from Hepatocellular Carcinoma: A Multi
      Institutional Retrospective Study (KROG 13-05).
AB  - Although the adrenal glands are not common sites of metastasis from
      hepatocellular carcinoma (HCC), this metastasis can be met in patients with
      advanced HCC in some clinical settings. However, the effectiveness of
      radiotherapy against such metastases is unclear. Therefore, we performed the
      present multi-institutional study to investigate tumor response, overall survival
      (OS), treatment-related toxicity, and prognostic factors after radiotherapy. We
      retrospectively reviewed 134 patients who completed a planned radiotherapy for
      their adrenal metastases. Complete response was noted in 6 (4.3%), partial
      response in 48 (34.0%), and stable disease in 78 patients (55.3%). The median OS
      was 12.8 months, and the 1-, 2-, and 5-year OS rates were 53.1%, 23.9%, and 9.3%,
      respectively. Grade 3 anorexia occurred in 2 patients, grade 3 diarrhea in 1, and
      grade 3 fatigue in 1. Multivariate analyses revealed that the following factors
      had significant effects on OS: controlled intrahepatic tumor; controlled
      extrahepatic metastasis; and Child-Pugh class A. Although patients with adrenal
      metastasis from HCC had poor OS, radiotherapy provided an objective response rate
      of 38.3% and disease stability of 93.6%, with minimal adverse events. Therefore,
      radiotherapy for these patients could represent a good treatment modality,
      especially for patients with controlled intrahepatic tumors, controlled
      extrahepatic metastasis, and good hepatic function. 

PMID- 27022933
TI  - Serum vitamin D status and in vitro fertilization outcomes: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To assess the correlation between serum 25-hydroxy vitamin D [25(OH)D]
      status and outcomes of in vitro fertilization (IVF) in infertile women through
      review systematically. METHODS: We used Embase, Pubmed, and Cochrane database to
      identify all studies that assessed the correlation between serum vitamin D levels
      and IVF outcomes in infertile women up until 30 June 2015, with the restricted
      language of English. We included studies that compared IVF outcomes between
      infertile women vitamin D <20 ng/ml and vitamin D >=20 ng/ml. The results were
      summarized using Stata 12.0 software. For studies reported dichotomous outcomes
      (clinical pregnancy rate and live birth rate), we pooled the relative risks
      ratios (RRs) and 95 % confidence intervals (CIs) in a random effects model.
      RESULTS: Our search resulted in the retrieval and screening of 134 studies. Of
      those, five studies were included in our meta-analysis. The risk for lower
      clinical pregnancy rate was not significantly increased in the deficient group
      (RR 0.88, 95 % CI 0.69-1.11). Lower vitamin D status was associated with lower
      live birth rate (RR 0.76, 95 % CI 0.61-0.93). CONCLUSION: There is no significant
      correlation between deficient serum vitamin D level and lower clinical pregnancy
      rate in infertile woman undergoing in vitro fertilization. On the other hand,
      deficient vitamin D level was related to lower live birth rate.

PMID- 27022934
TI  - Discordance between ultrasound and cell free DNA screening for monosomy X.
AB  - OBJECTIVE: Cell free DNA (cfDNA) testing has evolved as an important tool in
      prenatal screening for trisomy 21. It can also be used in screening for monosomy
      X. We perform a systemic review to determine the detection and false positive in
      screening for monosomy X and demonstrate a case that offers two possible
      explanations for the lower screening performance compared to trisomy 21. CASE: A
      31-year-old primigravida was referred to us due to an abnormal cfDNA test
      indicating monosomy X. However, the genitalia was male. An amniocentesis was done
      that indicated 46,X,idic(Y)(q11.21). SNP array analysis confirmed the Ypter
      q11.21 duplication. A phenotypically normal male baby was born at 40 weeks.
      Postnatal karyotyping of several pregnancy tissues was carried out. While in most
      samples the karyotype was 46,X,idic(Y)(q11.21), in the four placenta samples and
      in the amniotic membranes there was mosaicism of 46,X,idic(Y)(q11.21) and 45,X.
      DATA SOURCES: A search of the Medline and Embase database was done for articles
      about screening for monosomy X by cfDNA. We performed a systematic review to
      assess the detection and false-positive rate. RESULTS: Seven studies fulfilled
      the inclusion criteria. In summary, there were 153 pregnancies with monosomy X
      and 4116 euploid ones. The detection and false-positive rate was 94.1 and 0.53 %.
      CONCLUSION: Although the performance of cfDNA in prenatal screening for monosomy
      X is better than any other screening test, it is not comparable with invasive
      testing. One should be aware of the limitations especially if the ultrasound
      examination is contradictory with the cfDNA results.

PMID- 27022935
TI  - A randomized controlled experimental study of the efficacy of platelet-rich
      plasma and hyaluronic acid for the prevention of adhesion formation in a rat
      uterine horn model.
AB  - PURPOSE: Platelet-rich plasma (PRP) has been known to possess an efficacy in
      tissue regeneration. The aim of this study was to determine the role of PRP on
      post-operative adhesion formation in an experimental rat study. METHODS: Thirty
      Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP
      treatment groups and operated on for uterine horn adhesion modeling. Blood was
      collected to produce a PRP with platelet counts of 688 * 10(3)/MUL, and 1 ml of
      either hyaluronic acid gel or PRP was administered over the standard lesions,
      while the control group received no medication. The evaluation of post-operative
      adhesions was done on the 30th post-operative day. The location, extent, type,
      and tenacity of adhesions as well as total adhesion scores, tissue inflammation,
      fibrosis and transforming growth factor-1beta (TGF-1beta) expressions were
      evaluated. RESULTS: The total adhesion score was significantly lower in the PRP
      group (3.2 +/- 1.5) compared with the hyaluronic acid (5.0 +/- 1.3) and control
      (8.1 +/- 1.7) groups. The extent of the adhesions was significantly lower in the
      PRP group. There was no significant difference in the type and tenacity of
      adhesions between the hyaluronic acid and the PRP group. The level of
      inflammation was significantly higher in the control group than the others, while
      there was no difference between the PRP and hyaluronic acid groups. TGF-1beta
      expression was significantly lesser in the PRP group than the control and
      hyaluronic acid groups. CONCLUSIONS: PRP is more effective than hyaluronic acid
      treatment in preventing post-operative adhesion formation in an experimental rat
      uterine horn adhesion model.

PMID- 27022936
TI  - Nutrient Mitigation Efficiency in Agricultural Drainage Ditches: An Influence of
      Landscape Management.
AB  - Drainage systems are integral parts of agricultural landscapes and have the
      ability to intercept nutrient loading from runoff to surface water. This study
      investigated nutrient removal efficiency within replicated experimental
      agricultural drainage ditches during a simulated summer runoff event. Study
      objectives were to examine the influence of routine mowing of vegetated ditches
      on nutrient mitigation and to assess spatial transformation of nutrients along
      ditch length. Both mowed and unmowed ditch treatments decreased NO3 (-)-N by 79 %
      and 94 % and PO4 (3-) by 95 % and 98 %, respectively, with no significant
      difference in reduction capacities between the two treatments. This suggests
      occasional ditch mowing as a management practice would not undermine nutrient
      mitigation capacity of vegetated drainage ditches. 

PMID- 27022938
TI  - Awareness of Pre-exposure Prophylaxis for HIV, Willingness to Use It and
      Potential Barriers or Facilitators to Uptake Among Men Who Have Sex with Men in
      Spain.
AB  - There is a lack of data on pre-exposure prophylaxis (PrEP) effectiveness in
      Spain. We described the awareness of and willingness to use PrEP and examined
      potential barriers and facilitators to their use among men who have sex with men
      recruited either online or in voluntary HIV testing centers in Spain. Nearly a
      third of men (28.7 %) were aware of PrEP and 57.6 % said they would be willing to
      use it if available, 16.6 % saying they would be unwilling to use PrEP and 25.8 %
      not being sure. Men who had heard of PrEP were more forceful in their opinions on
      willingness to use PrEP (willing/not willing: 29.8 %/32.6 % vs. don't know: 21.8
      %). The greatest consensus regarding more acceptable PrEP attributes was in the
      mode of delivery and its cost. Doctors (91 %) or pharmacists (85.3 %) were the
      preferred providers. The results confirm the need to inform and educate on PrEP
      and define implementation strategies.

PMID- 27022937
TI  - The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria
      Parasites.
AB  - The phist gene family has members identified across the Plasmodium genus, defined
      by the presence of a domain of roughly 150 amino acids having conserved aromatic
      residues and an all alpha-helical structure. The family is highly amplified in P.
      falciparum, with 65 predicted genes in the genome of the 3D7 isolate. In
      contrast, in the rodent malaria parasite P. berghei 3 genes are identified, one
      of which is an apparent pseudogene. Transcripts of the P. berghei phist genes are
      predominant in schizonts, whereas in P. falciparum transcript profiles span
      different asexual blood stages and gametocytes. We pursued targeted disruption of
      P. berghei phist genes in order to characterize a simplistic model for the
      expanded phist gene repertoire in P. falciparum. Unsuccessful attempts to disrupt
      P. berghei PBANKA_114540 suggest that this phist gene is essential, while
      knockout of phist PBANKA_122900 shows an apparent normal progression and non
      essential function throughout the life cycle. Epitope-tagging of P. falciparum
      and P. berghei phist genes confirmed protein export to the erythrocyte cytoplasm
      and localization with a punctate pattern. Three P. berghei PEXEL/HT-positive
      exported proteins exhibit at least partial co-localization, in support of a
      common vesicular compartment in the cytoplasm of erythrocytes infected with
      rodent malaria parasites. 

PMID- 27022939
TI  - Infant and Young Child Feeding Counseling, Decision-Making, and Practices Among
      HIV-Infected Women in Malawi's Option B+ Prevention of Mother-to-Child
      Transmission Program: A Mixed Methods Study.
AB  - This study examined infant and young child feeding (IYCF) counseling, decision
      making, and practices among HIV-infected women with children 0-23 months
      participating in Malawi's Option B+ prevention of mother-to-child transmission
      (PMTCT) program. We conducted 160 survey interviews, 32 in-depth interviews, and
      32 observations of PMTCT visits. Surveys indicated that exclusive breastfeeding
      was common (75 %) among children <6 months, while minimum dietary diversity (41
      %) and minimum acceptable diet (40 %) for children 6-23 months occurred less
      often. In-depth interviews supported these findings. Most women felt comfortable
      with current breastfeeding recommendations, but chronic food insecurity made it
      difficult for them to follow complementary feeding guidelines. Women trusted IYCF
      advice from health workers, but mainly received it during pregnancy. During
      observations of postnatal PMTCT visits, health workers infrequently advised on
      breastfeeding (41 % of visits) or complementary feeding (29 % of visits). This
      represents a missed opportunity for health workers to support optimal IYCF
      practices within Option B+.

PMID- 27022940
TI  - SIRT1 prevents hyperuricemia via the PGC-1alpha/PPARgamma-ABCG2 pathway.
AB  - Silent information regulator T1 (SIRT1) plays several key roles in the regulation
      of lipid and glucose homoeostasis. In this study, we investigated the potential
      role of SIRT1 in hyperuricemia and explored possible mechanisms. Significant
      hyperuricemia was detected in C57BL/6 mice treated with oxonate and yeast
      polysaccharide. Resveratrol (RSV), a specific SIRT1 activator, was administered
      to the mice. SIRT1 suppressed the increased serum uric acid level but up
      regulated the expression of urate transporter ATP-binding cassette subfamily G
      member 2 (ABCG2) in the ileum of hyperuricemic mice. In a human colon carcinoma
      cell line, SIRT1 promoted ABCG2 production through the deacetylation of
      peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1alpha (PGC
      1alpha), which then activated the effectors of PPARgamma. Interestingly, the
      SIRT1-induced up-regulation of ABCG2 was significantly inhibited when PGC-1alpha
      or PPARgamma was blocked by siRNA transfection. Our data demonstrated that SIRT1
      and its activator, RSV, have clear anti-hyperuricemia functions in this mouse
      model. One possible mechanism is the activation of ABCG2 in the ileum through the
      PGC-1alpha/PPARgamma pathway. 

PMID- 27022941
TI  - Post-prandial anorexigenic gut peptide, appetite and glucometabolic responses at
      different eating rates in obese patients undergoing laparoscopic sleeve
      gastrectomy.
AB  - Although different hypotheses have been proposed, the underlying mechanism(s) of
      the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still
      unknown. The aim of this study was to determine whether eating the same meal at
      different rates (fast vs. slow feeding) evokes different post-prandial
      anorexigenic gut peptide responses in ten obese patients undergoing LSG.
      Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were
      measured before and 3 months after LSG. Visual analogue scales were used to
      evaluate the subjective feelings of hunger and satiety. Irrespective of the
      operative state, either fast or slow feeding did not stimulate GLP-1 release (vs.
      0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding
      only after LSG. There were no differences in post-prandial levels of GLP-1 when
      comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of
      PYY after fast or slow feeding were higher in post, rather than pre-operative
      state, with no differences when comparing PYY release after fast and slow
      feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0
      min) by food intake. Fast feeding evoked a higher satiety than slow feeding in
      both pre- and post-operative states, with no differences in hunger. In both pre-
      and post-operative states, there were similar responses for hunger and satiety
      after food intake. Finally, LSG improved insulin resistance after either fast or
      slow feeding. These (negative) findings would suggest a negligible contribution
      of the anorexigenic gut peptide responses in LSG-induced weight loss.

PMID- 27022942
TI  - Optical Coherence Tomography Angiography of Macular Telangiectasia Type 2.
AB  - Macular telangiectasia type 2 (MacTel2) is a disease of the central macula that
      affects all microvascular layers of the retina and also includes
      neovascularization arising from both the retinal and choroidal circulations. As a
      result, MacTel2 is the ideal macular disease for imaging with optical coherence
      tomography (OCT) angiography (OCTA). In MacTel2, the earliest changes in the
      retinal microvasculature involve the temporal aspect of the parafoveal deep
      capillary plexus, and OCTA reveals these changes. Microvascular abnormalities
      then extend circumferentially around the fovea and into the superficial capillary
      plexus. As the disease progresses, dilated anastomoses form between the
      superficial and deep capillary plexuses, and the retina becomes more atrophic,
      with the formation of cysts and the loss of photoreceptor outer segments. In some
      patients, the anastomoses between the plexuses progress to subretinal
      neovascularization, with connections to the choroidal vasculature. OCTA provides
      clear advantages over current imaging modalities, such as traditional OCT
      imaging, reflectance fundus imaging, autofluorescence imaging, fluorescein
      angiography, and indocyanine green angiography, for MacTel2 because it is safer,
      cheaper, more comfortable for the patient, and more easily repeatable, it can be
      performed during follow-up visits, and it produces both intensity-based OCT
      images and flow-based images, which allow for visualization of the macular
      microvasculature. OCTA is the only imaging modality needed for the diagnosis and
      monitoring of MacTel2 at every stage of disease progression. 

PMID- 27022945
TI  - Corrigendum: Climate induces seasonality in pneumococcal transmission.

PMID- 27022946
TI  - Strengthening links between GP training and academic primary care.

PMID- 27022944
TI  - Effects of radiation on metastasis and tumor cell migration.
AB  - It is well known that tumor cells migrate from the primary lesion to distant
      sites to form metastases and that these lesions limit patient outcome in a
      majority of cases. However, the extent to which radiation influences this process
      and to which migration in turn alters radiation response remains controversial.
      There are preclinical and clinical reports showing that focal radiotherapy can
      both increase the development of distant metastasis, as well as that it can
      induce the regression of established metastases through the abscopal effect. More
      recently, preclinical studies have suggested that radiation can attract migrating
      tumor cells and may, thereby, facilitate tumor recurrence. In this review, we
      summarize these phenomena and their potential mechanisms of action, and evaluate
      their significance for modern radiation therapy strategies.

PMID- 27022943
TI  - Melatonin role preventing steatohepatitis and improving liver transplantation
      results.
AB  - Liver steatosis is a prevalent process that is induced due to alcoholic or non
      alcoholic intake. During the course of these diseases, the generation of reactive
      oxygen species, followed by molecular damage to lipids, protein and DMA occurs
      generating organ cell death. Transplantation is the last-resort treatment for the
      end stage of both acute and chronic hepatic diseases, but its success depends on
      ability to control ischemia-reperfusion injury, preservation fluids used, and
      graft quality. Melatonin is a powerful endogenous antioxidant produced by the
      pineal gland and a variety of other because of its efficacy in organs; melatonin
      has been investigated to improve the outcome of organ transplantation by reducing
      ischemia-reperfusion injury and due to its synergic effect with organ
      preservation fluids. Moreover, this indolamine also prevent liver steatosis. That
      is important because this disease may evolve leading to an organ transplantation.
      This review summarizes the observations related to melatonin beneficial actions
      in organ transplantation and ischemic-reperfusion models.

PMID- 27022947
TI  - Particulate Matter Exposure and Preterm Birth: Estimates of U.S. Attributable
      Burden and Economic Costs.
AB  - BACKGROUND: Preterm birth (PTB) rates (11.4% in 2013) in the United States remain
      high and are a substantial cause of morbidity. Studies of prenatal exposure have
      associated particulate matter <= 2.5 MUm in diameter (PM2.5) and other ambient
      air pollutants with adverse birth outcomes; yet, to our knowledge, burden and
      costs of PM2.5-attributable PTB have not been estimated in the United States.
      OBJECTIVES: We aimed to estimate burden of PTB in the United States and economic
      costs attributable to PM2.5 exposure in 2010. METHODS: Annual deciles of PM2.5
      were obtained from the U.S. Environmental Protection Agency. We converted PTB
      odds ratio (OR), identified in a previous meta-analysis (1.15 per 10 MUg/m3 for
      our base case, 1.07-1.16 for low- and high-end scenarios) to relative risk (RRs),
      to obtain an estimate that better represents the true relative risk. A reference
      level (RL) of 8.8 MUg/m3 was applied. We then used the RR estimates and county
      level PTB prevalence to quantify PM2.5-attributable PTB. Direct medical costs
      were obtained from the 2007 Institute of Medicine report, and lost economic
      productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss,
      and well-established relationships of IQ loss with LEP. All costs were calculated
      using 2010 dollars. RESULTS: An estimated 3.32% of PTBs nationally (corresponding
      to 15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5 > 8.8 MUg/m3).
      Attributable PTBs cost were estimated at $5.09 billion [sensitivity analysis
      (SA): $2.43-9.66 B], of which $760 million were spent for medical care (SA: $362
      M-1.44 B). The estimated PM2.5 attributable fraction (AF) of PTB was highest in
      urban counties, with highest AFs in the Ohio Valley and the southern United
      States. CONCLUSIONS: PM2.5 may contribute substantially to burden and costs of
      PTB in the United States, and considerable health and economic benefits could be
      achieved through environmental regulatory interventions that reduce PM2.5
      exposure in pregnancy. Citation: Trasande L, Malecha P, Attina TM. 2016.
      Particulate matter exposure and preterm birth: estimates of U.S. attributable
      burden and economic costs. Environ Health Perspect 124:1913-1918;
      http://dx.doi.org/10.1289/ehp.1510810.

PMID- 27022948
TI  - Preeclampsia and Blood Pressure Trajectory during Pregnancy in Relation to
      Vitamin D Status.
AB  - Every tenth pregnancy is affected by hypertension, one of the most common
      complications and leading causes of maternal death worldwide. Hypertensive
      disorders in pregnancy include pregnancy-induced hypertension and preeclampsia.
      The pathophysiology of the development of hypertension in pregnancy is unknown,
      but studies suggest an association with vitamin D status, measured as 25
      hydroxyvitamin D (25(OH)D). The aim of this study was to investigate the
      association between gestational 25(OH)D concentration and preeclampsia, pregnancy
      induced hypertension and blood pressure trajectory. This cohort study included
      2000 women. Blood was collected at the first (T1) and third (T3) trimester (mean
      gestational weeks 10.8 and 33.4). Blood pressure at gestational weeks 10, 25, 32
      and 37 as well as symptoms of preeclampsia and pregnancy-induced hypertension
      were retrieved from medical records. Serum 25(OH)D concentrations (LC-MS/MS) in
      T1 was not significantly associated with preeclampsia. However, both 25(OH)D in
      T3 and change in 25(OH)D from T1 to T3 were significantly and negatively
      associated with preeclampsia. Women with a change in 25(OH)D concentration of
      >=30 nmol/L had an odds ratio of 0.22 (p = 0.002) for preeclampsia. T1 25(OH)D
      was positively related to T1 systolic (beta = 0.03, p = 0.022) and T1 diastolic
      blood pressure (beta = 0.02, p = 0.016), and to systolic (beta = 0.02, p = 0.02)
      blood pressure trajectory during pregnancy, in adjusted analyses. There was no
      association between 25(OH)D and pregnancy-induced hypertension in adjusted
      analysis. In conclusion, an increase in 25(OH)D concentration during pregnancy of
      at least 30 nmol/L, regardless of vitamin D status in T1, was associated with a
      lower odds ratio for preeclampsia. Vitamin D status was significantly and
      positively associated with T1 blood pressure and gestational systolic blood
      pressure trajectory but not with pregnancy-induced hypertension. 

PMID- 27022949
TI  - Generation of Recombinant Monoclonal Antibodies from Immunised Mice and Rabbits
      via Flow Cytometry and Sorting of Antigen-Specific IgG+ Memory B Cells.
AB  - Single B cell screening strategies, which avoid both hybridoma fusion and
      combinatorial display, have emerged as important technologies for efficiently
      sampling the natural antibody repertoire of immunized animals and humans. Having
      access to a range of methods to interrogate different B cell subsets provides an
      attractive option to ensure large and diverse panels of high quality antibody are
      produced. The generation of multiple antibodies and having the ability to find
      rare B cell clones producing IgG with unique and desirable characteristics
      facilitates the identification of fit-for-purpose molecules that can be developed
      into therapeutic agents or research reagents. Here, we describe a multi-parameter
      flow cytometry single-cell sorting technique for the generation of antigen
      specific recombinant monoclonal antibodies from single IgG+ memory B cells. Both
      mouse splenocytes and rabbit PBMC from immunised animals were used as a source of
      B cells. Reagents staining both B cells and other unwanted cell types enabled
      efficient identification of class-switched IgG+ memory B cells. Concurrent
      staining with antigen labelled separately with two spectrally-distinct
      fluorophores enabled antigen-specific B cells to be identified, i.e. those which
      bind to both antigen conjugates (double-positive). These cells were then
      typically sorted at one cell per well using FACS directly into a 96-well plate
      containing reverse transcriptase reaction mix. Following production of cDNA, PCR
      was performed to amplify cognate heavy and light chain variable region genes and
      generate transcriptionally-active PCR (TAP) fragments. These linear expression
      cassettes were then used directly in a mammalian cell transfection to generate
      recombinant antibody for further testing. We were able to successfully generate
      antigen-specific recombinant antibodies from both the rabbit and mouse IgG+
      memory B cell subset within one week. This included the generation of an anti
      TNFR2 blocking antibody from mice with an affinity of 90 pM. 

PMID- 27022950
TI  - Rotating waves in simple scalar excitable media: approximations and numerical
      solutions.
AB  - Rotating waves, in a two-dimensional annular region, are studied using a number
      of semi-analytical methods. For our kinetics, we use a simple one-variable phase
      model that arises as the normal form in the transition between excitability and
      oscillation at a saddle-node invariant circle (SNIC) bifurcation. After deriving
      asymptotic expressions for the scalar dispersion relationship, we use this to
      compare the approximations to a direct numerical simulation of the governing
      nonlinear partial differential equation. All of the approximation methods are
      based on writing the full solution [Formula: see text] as [Formula: see text] +
      "perturbation" terms where V is some function and [Formula: see text] is the
      radial phase shift. Finding an expression for the radial phase shift is the main
      aim of this paper. It is found that the total twist of the spiral is not a
      monotone function of the excitability. The largest twist occurs in the vicinity
      of the transition from excitable to oscillatory behavior.

PMID- 27022951
TI  - Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced
      Pluripotent Stem Cells.
AB  - Nasal epithelial cells (NECs) are the part of the airways that respond to air
      pollutants and are the first cells infected with respiratory viruses. They are
      also involved in many airway diseases through their innate immune response and
      interaction with immune and airway stromal cells. NECs are of particular interest
      for studies in children due to their accessibility during clinical visits. Human
      induced pluripotent stem cells (iPSCs) have been generated from multiple cell
      types and are a powerful tool for modeling human development and disease, as well
      as for their potential applications in regenerative medicine. This is the first
      protocol to lay out methods for successful generation of iPSCs from NECs derived
      from pediatric participants for research purposes. It describes how to obtain
      nasal epithelial cells from children, how to generate primary NEC cultures from
      these samples, and how to reprogram primary NECs into well-characterized iPSCs.
      Nasal mucosa samples are useful in epidemiological studies related to the effects
      of air pollution in children, and provide an important tool for studying airway
      disease. Primary nasal cells and iPSCs derived from them can be a tool for
      providing unlimited material for patient-specific research in diverse areas of
      airway epithelial biology, including asthma and COPD research. 

PMID- 27022953
TI  - Mother's Emotional and Posttraumatic Reactions after a Preterm Birth: The Mother
      Infant Interaction Is at Stake 12 Months after Birth.
AB  - OBJECTIVES: Very preterm infants are known to be at risk of developmental
      disabilities and behavioural disorders. This condition is supposed to alter
      mother-infant interactions. Here we hypothesize that the parental coping with the
      very preterm birth may greatly influence mother-infant interactions. METHODS: 100
      dyads were included in 3 university hospitals in France. Preterm babies at higher
      risk of neurodevelopmental sequelae (PRI>10) were excluded to target the maternal
      determinants of mother-infant interaction. We report the follow-up of this cohort
      during 1 year after very preterm birth, with regular assessment of infant somatic
      state, mother psychological state and the assessment of mother-infant interaction
      at 12 months by validated scales (mPPQ, HADS, EPDS, PRI, DDST and PIPE). RESULTS:
      We show that the intensity of post-traumatic reaction of the mother 6 months
      after birth is negatively correlated with the quality of mother-infant
      interaction at 12 months. Moreover, the anxious and depressive symptoms of the
      mother 6 and 12 months after birth are also correlated with the quality of mother
      infant interaction at 12 months. By contrast, this interaction is not influenced
      by the initial affective state of the mother in the 2 weeks following birth. In
      this particular population of infants at low risk of sequelae, we also show that
      the quality of mother-infant interaction is not correlated with the assessment of
      the infant in the neonatal period but is correlated with the fine motor skills of
      the baby 12 months after birth. CONCLUSIONS: This study suggests that mothers'
      psychological condition has to be monitored during the first year of very preterm
      infants' follow-up. It also suggests that parental interventions have to be
      proposed when a post-traumatic, anxious or depressive reaction is suspected.

PMID- 27022952
TI  - Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9
      Predicts Survival and Response to Temozolomide in Patients with Primary
      Glioblastoma.
AB  - BACKGROUND: Glioblastoma multiform (GBM) is the most common malignant primary
      brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ
      chemotherapy is the current standard of care for patients with GBM. Matrix
      metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key
      modulators of tumor invasion and metastasis due to their ECM degradation
      capacity. The aim of the present study was to identify the most informative MMP
      member in terms of prognostic and predictive ability for patients with primary
      GBM. METHOD: The mRNA expression profiles of all MMP genes were obtained from the
      Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia
      Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also
      examined by pyrosequencing. The correlation of MMP9 expression with tumor
      progression was explored in glioma specimens of all grades. Kaplan-Meier analysis
      and Cox proportional hazards regression models were used to investigate the
      association of MMP9 expression with survival and response to temozolomide.
      RESULTS: MMP9 was the only significant prognostic factor in three datasets for
      primary glioblastoma patients. Our results indicated that MMP9 expression is
      correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was
      correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and
      MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS:
      p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited
      from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status.
      CONCLUSIONS: Patients with primary GBMs with low MMP9 expression may have longer
      survival and may benefit from temozolomide chemotherapy.

PMID- 27022954
TI  - QTLs for Woolly Poplar Aphid (Phloeomyzus passerinii L.) Resistance Detected in
      an Inter-Specific Populus deltoides x P. nigra Mapping Population.
AB  - The genus Populus represents one of the most economically important groups of
      forest trees. It is composed by approximately 30 species used for wood and non
      wood products, phytoremediation and biomass. Poplar is subjected to several
      biological and environmental threats although, compared to annual crops, we know
      far less about the genetic bases of biotic stress resistance. Woolly poplar aphid
      (Phloeomyzus passerinii) is considered a main pest of cultivated poplars in
      European and American countries. In this work we present two high density linkage
      maps in poplar obtained by a genotyping by sequencing (GBS) approach and the
      identification of QTLs involved in Ph. passerinii resistance. A total of 5,667
      polymorphic markers (5,606 SNPs and 61 SSRs) identified on expressed sequences
      have been used to genotype 131 plants of an F1 population P *canadensis obtained
      by an interspecific mate between Populus deltoides (resistant to woolly poplar
      aphid) and Populus nigra (susceptible to woolly poplar aphid). The two linkage
      maps, obtained following the two-way pseudo-testcross mapping strategy, have been
      used to investigate the genetic bases of woolly poplar aphid resistance. One
      major QTL and two QTLs with minor effects (mapped on LGV, LGXVI and LG XIX)
      explaining the 65.8% of the genetic variance observed in the progeny in response
      to Ph. passerinii attack were found. The high density coverage of functional
      markers allowed the identification of three genes belonging to disease resistance
      pathway as putative candidates for P. deltoides resistance to woolly poplar
      aphid. This work is the first report on genetic of woolly poplar aphid genetic
      resistance and the resistant loci associated markers identified represent a
      valuable tool in resistance poplar breeding programs. 

PMID- 27022955
TI  - Neuroimaging in Blast-Related Mild Traumatic Brain Injury.
AB  - OBJECTIVE: To summarize imaging findings in blast-related mild traumatic brain
      injury. DESIGN: Our structured review of the literature yielded 5 structural
      magnetic resonance imaging (sMRI), 18 diffusion tensor imaging, 9 functional
      magnetic resonance imaging (fMRI), 3 positron emission tomography, 4
      magnetoencephalography, 2 electroencephalography, and 1 single-positron emission
      computerized tomography studies. RESULTS: Four of the 5 sMRI studies reported
      decreased cortical thickness and decreased thalamus and amygdala volume.
      Diffusion tensor imaging studies showed abnormal diffusion within white matter
      tracts commonly associated with traumatic brain injury, including the corpus
      callosum (8 of the 18) and superior longitudinal fasciculus (8 of the 18).
      Resting-state fMRI studies reported a variety of functional network differences.
      Other functional imaging studies showed diffuse changes in activity, especially
      in the frontal, parietal, temporal, and cingulate regions. CONCLUSION: Vast
      variation in the sample, design, and measurement features across studies
      precludes salient conclusions regarding the effectiveness of neuroimaging to
      assess outcomes and elucidate pathomechanisms. The inherent spatial heterogeneity
      of mild traumatic brain injury pathology presents a major challenge to meaningful
      convergence across and generalizable inferences. Approaches to standardize
      methodology and facilitate access to data and integration across studies hold
      promise for enhancing our understanding of this complex brain disorder, but can
      only bear fruit if they are actually consistently implemented.

PMID- 27022956
TI  - Characteristics and Concerns of Caregivers of Adults With Traumatic Brain Injury.
AB  - OBJECTIVE: To describe the characteristics of caregivers of adults with traumatic
      brain injury (TBI) and their concerns in the first months after community
      discharge of the TBI survivor. DESIGN: Secondary analysis of data collected
      during a parallel-group randomized controlled trial. SETTING: Community.
      PARTICIPANTS: A total of 153 consecutively enrolled caregivers of adults with
      moderate to severe TBI discharged to the community following acute and/or
      rehabilitation care at a Level I trauma center with 71 caregivers in the
      treatment group identifying concerns as part of the intervention procedures. MAIN
      MEASURES: Caregiver demographics, caregiver-survivor relationship
      characteristics, caregiver activity changes, and concerns targeted by caregivers
      for education and problem-solving via biweekly phone calls. RESULTS: Thirty-nine
      percent of caregivers were spouses and 35% parents. Sixty-five percent lived in
      the same house as the survivor preinjury with 86% in touch daily to several times
      per week. Concerns targeted by more than one-third of caregivers related to
      managing their emotional adjustment, strategies for getting things done, managing
      survivor emotions and behaviors, and engaging in healthful habits. CONCLUSIONS:
      Caregivers of TBI survivors targeted personal concerns relating to their own
      emotional adjustment and participation as well as concerns relating to symptoms
      and recovery of the TBI survivor to address through education and problem
      solving.

PMID- 27022957
TI  - Actigraphically Measured Sleep-Wake Behavior After Mild Traumatic Brain Injury: A
      Case-Control Study.
AB  - OBJECTIVE: To characterize and compare the sleep-wake behavior of individuals
      following a mild traumatic brain injury (mTBI) with that of noninjured healthy
      controls. SETTING: Community. PARTICIPANTS: Fourteen participants with a recent
      mTBI (Mage = 28.07; SD = 10.45; n = 10 females) and 34 noninjured controls (Mage
      = 23.70; SD = 7.30; n = 31 females). DESIGN: Cross-sectional. MAIN MEASURES:
      Battery of subjective sleep measures and 14 days of sleep-wake monitoring via
      actigraphy (objective measurement) and concurrent daily sleep diary. RESULTS:
      Participants who had sustained an mTBI self-reported significantly higher sleep
      related impairment, poorer nightly sleep quality, and more frequently met
      criteria for clinical insomnia, compared with controls (d = 0.76-1.11, large
      effects). The only significant between-group difference on objective sleep
      metrics occurred on sleep timing. On average, people with a recent history of
      mTBI fell asleep and woke approximately 1 hour earlier than did the controls (d =
      0.62-0.92, medium to large effects). CONCLUSION: Participants with a history of
      mTBI had several subjective sleep complaints but relatively few objective sleep
      changes with the exception of earlier sleep timing. Future research is needed to
      understand the clinical significance of these findings and how these symptoms can
      be alleviated. Interventions addressing subjective sleep complaints (eg,
      cognitive behavior therapy for insomnia) should be tested in this population.

PMID- 27022958
TI  - Impact of Early Follow-Up Intervention on Parent-Reported Postconcussion
      Pediatric Symptoms: A Feasibility Study.
AB  - OBJECTIVES: To investigate the effectiveness and feasibility of early
      intervention telephone counseling with parents in limiting postconcussion
      symptoms and impacts on children and youth. SETTING: Recruitment occurred
      postdischarge from one pediatric emergency department. PARTICIPANTS: Sixty-six
      parents of children aged 5 to 16 years with a diagnosis of a concussion injury.
      DESIGN: A pilot, randomized controlled study compared the efficacy of telephone
      counseling (reviewing symptom management and return to activity with parents at 1
      week and 1 month postinjury) with usual care (no formalized follow-up). MAIN
      MEASURES: The Post-Concussion Symptom Inventory and the Family Burden of Injury
      Interview administered with parents by a blinded therapist at 3 months
      postinjury. RESULTS: No significant difference between the groups at 3 months
      postinjury in postconcussion symptoms (P = .67) and family stress (P = .647).
      CONCLUSION: The findings suggest that the early counseling intervention strategy
      trialed herein may not be effective for children and youth who experience
      significant postconcussion symptoms. Further research is needed to determine
      whether more intensive and integrated care would better serve children.

PMID- 27022959
TI  - Prognostic Markers for Poor Recovery After Mild Traumatic Brain Injury in Older
      Adults: A Pilot Cohort Study.
AB  - OBJECTIVE: To identify prognostic markers associated with poor recovery from mild
      traumatic brain injury (MTBI) in older adults. SETTING: Three Ontario emergency
      departments. PARTICIPANTS: Forty-nine participants aged 65 years and older that
      visited an emergency department for MTBI. DESIGN: Pilot prospective cohort study.
      MAIN MEASURES: Recovery from MTBI determined using the Rivermead Postconcussion
      symptom Questionnaire, the Glasgow Outcomes Scale-Extended, physical and mental
      health functioning (SF-12), and a single question on self-rated recovery assessed
      by telephone shortly after emergency department visit (baseline) and again 6
      months later. Predictors were measured at baseline. RESULTS: Markers potentially
      associated with poor recovery included reporting worse health 1 year before the
      injury, poor expectations for recovery, depression, and fatigue. CONCLUSION:
      Recovery after MTBI in older adults may be associated more with psychosocial than
      with biomedical or injury-related factors.

PMID- 27022960
TI  - Does Co-Occurring Traumatic Brain Injury Affect VHA Outpatient Health Service
      Utilization and Associated Costs Among Veterans With Posttraumatic Stress
      Disorder? An Examination Based on VHA Administrative Data.
AB  - OBJECTIVE: To examine whether a traumatic brain injury (TBI) diagnosis was
      associated with increased outpatient service utilization and associated costs
      among Iraq and Afghanistan (Operation Enduring Freedom [OEF]/Operation Iraqi
      Freedom [OIF]/Operation New Dawn [OND]) War veterans with posttraumatic stress
      disorder (PTSD) who used Veterans Health Affairs (VHA) care in a 1-year period.
      SETTING: N/A. PARTICIPANTS: OEF/OIF/OND veterans with a diagnosis of PTSD and/or
      TBI who utilized VHA services during fiscal year 2012 (N = 164 644). DESIGN:
      Observational study using VHA administrative data. MAIN MEASURES: Outpatient VHA
      utilization (total and by category of care) and associated costs (total and by VA
      Health Economic Resource Center cost category). RESULTS: Veterans in the comorbid
      PTSD/TBI group had significantly more total outpatient appointment than veterans
      with PTSD but no TBI. This pattern held for all categories of care except
      orthopedics. The comorbid TBI/PTSD group ($5769) incurred greater median
      outpatient healthcare costs than the PTSD ($3168) or TBI-alone ($2815) group.
      CONCLUSIONS: Co-occurring TBI increases the already high level of healthcare
      utilization by veterans with PTSD, suggesting that OEF/OIF/OND veterans with
      comorbid PTSD/TBI have complex and wide-ranging healthcare needs.

PMID- 27022961
TI  - Compensatory Cognitive Training for Operation Enduring Freedom/Operation Iraqi
      Freedom/Operation New Dawn Veterans With Mild Traumatic Brain Injury.
AB  - OBJECTIVE: The purpose of the study was to evaluate the efficacy of group-based
      compensatory cognitive training (CCT) for Operation Enduring Freedom
      (OEF)/Operation Iraqi Freedom(OIF)/Operation New Dawn (OND) Veterans with a
      history of mild traumatic brain injury. METHOD: One hundred nineteen OEF/OIF/OND
      Veterans with history of mild traumatic brain injury participated at 3 sites, and
      50 of the Veterans were randomized to CCT group, while 69 Veterans were
      randomized to the usual care control group. The CCT group participated in 10
      weeks of CCT. Both CCT and usual care groups were assessed at baseline, 5 weeks
      (midway through CCT), 10 weeks (immediately following CCT), and 15 weeks (5-week
      follow-up) on measures of subjective cognitive complaints, use of cognitive
      strategies, psychological functioning, and objective cognitive performance.
      RESULTS: Veterans who participated in CCT reported significantly fewer cognitive
      and memory difficulties and greater use of cognitive strategies. They also
      demonstrated significant improvements on neurocognitive tests of attention,
      learning, and executive functioning, which were 3 of the cognitive domains
      targeted in CCT. CONCLUSIONS: Findings indicate that training in compensatory
      cognitive strategies facilitates behavioral change (ie, use of cognitive
      strategies) as well as both subjective and objective improvements in targeted
      cognitive domains.

PMID- 27022962
TI  - Preenlistment and Early Service Risk Factors for Traumatic Brain Injury in the
      Army and Marine Corps: FY 2002-2010.
AB  - OBJECTIVE: To determine the preenlistment and early service risk factors for
      traumatic brain injury (TBI)-related disability in Army and Marine Corps service
      members. DESIGN: Matched case-control design. MAIN OUTCOME: TBI disability
      discharges. SUBJECTS: Army and Marine Corps service members with an enlistment
      record and disability discharge for TBI were included as cases. Controls were
      selected from the enlisted population with no disability evaluation record and
      were matched on fiscal year of enlistment, sex, and service at a ratio of 5:1.
      RESULTS: Older age at enlistment resulted in a significantly increased risk for
      TBI disability in the crude and adjusted models (adjusted odds ratio [aOR] =
      1.49; 95% confidence interval [CI], 1.16-1.91). An enlistment military
      occupational specialty (MOS) with a combat arms designation resulted in an almost
      3-fold increased odds of TBI disability compared with other MOS categories (aOR =
      2.75; 95% CI, 2.46-3.09). This remained a significant risk factor for TBI
      disability in the multivariate model (aOR = 2.74; 95% CI, 2.45-3.08). CONCLUSION:
      Results from this study help inform the existing body of military TBI research by
      highlighting the preenlistment demographic and early service risk factors for TBI
      disability. Further research into the role of age on TBI disability in the
      military is merited.

PMID- 27022963
TI  - Risk of Stroke Among Older Medicare Antidepressant Users With Traumatic Brain
      Injury.
AB  - OBJECTIVE: To estimate the risk of stroke associated with new antidepressant use
      among older adults with traumatic brain injury (TBI). PARTICIPANTS: A total of 64
      214 Medicare beneficiaries aged 65 years or older meeting inclusion criteria and
      hospitalized with a TBI during 2006 to 2010. DESIGN: New user design. Generalized
      estimating equations were used to estimate the relative risks (RRs) of stroke.
      MAIN MEASURES: Primary exposure was new antidepressant use following TBI
      identified through Medicare part D claims. The primary outcome was stroke
      following TBI. Ischemic and hemorrhagic strokes were secondary outcomes. RESULTS:
      A total of 20 859 (32%) beneficiaries used an antidepressant at least once
      following TBI. Selective serotonin reuptake inhibitors accounted for the majority
      of antidepressant use. Selective serotonin reuptake inhibitor use was associated
      with an increased risk of hemorrhagic stroke (RR, 1.26; 95% confidence interval
      [CI], 1.06-1.50) but not ischemic stroke (RR, 1.04; 95% CI, 0.94-1.15). The
      selective serotonin reuptake inhibitors escitalopram (RR, 1.33; 95% CI, 1.02
      1.74) and sertraline (RR, 1.46; 95% CI, 1.10-1.94) were associated with an
      increase in the risk of hemorrhagic stroke. CONCLUSION: Findings from this study
      will aid prescribers in choosing appropriate antidepressants to treat depression
      in older adults with TBI.

PMID- 27022964
TI  - Methadone as first-line opioid treatment for cancer pain in a developing country
      palliative care unit.
AB  - PURPOSE: The use of methadone for cancer pain is limited by the need of expertise
      and close titration due to variable half-life. Yet, it is a helpful palliative
      strategy in low-resources countries given its long-acting effect at low cost and
      worth additional study. Our aim was to describe the prescription and outcomes of
      methadone as a first-line treatment for cancer pain in a tertiary palliative care
      unit (PCU) in Argentina. METHODS: Retrospective review of medical records of
      patients with moderate to severe cancer pain seen at the PCU in 1-year period,
      who initiated strong opioids at the first consultation. Data collected during the
      first month of treatment included disease and pain characteristics, initial and
      final opioid type and dose and need for opioid rotation. RESULTS: Methadone was
      the most frequent opioid both at the initial and last assessment (71 and 66 % of
      the prescriptions). In all, treatment with strong opioids provided considerable
      decrease in pain intensity (p < 0.001) with low and stable opioid dose. Median
      and interquartile range (IR) of oral morphine equivalent daily dose (OMEDD) was
      26 (16-32) and 39 (32-55) mg for initial and final assessments, respectively (p =
      0.3). In patients initiated with methadone, the median (IR) daily methadone dose
      was 5 (4-6) mg at first and 7.5 (6-10) mg at final assessment, and the median
      (IR) index of opioid escalation was 0 (0-4) mg; (p < 0.05). Patients on methadone
      underwent less percentage of opioid rotation (15 versus 50 %; p < 0.001) and
      longer time to rotation (20.6 +/- 4.4 versus 9.0 +/- 2.7 days; p < 0.001) than
      patients on other opioids. CONCLUSIONS: Results indicate the preference of
      methadone as first-line strong opioid treatment in a PCU, providing good pain
      relief at low doses with low need for rotation. Several considerations about the
      costs of strong opioids in the region are given.

PMID- 27022965
TI  - Burden of symptoms associated with development of metastatic bone disease in
      patients with breast cancer.
AB  - PURPOSE: Women with breast cancer frequently develop painful bone metastases.
      This retrospective study was designed to longitudinally characterize patterns of
      patient-reported symptoms among patients with breast cancer relative to the
      diagnosis of bone metastases. METHODS: Patient records were identified from the
      Oncology Services Comprehensive Electronic Records (OSCER) database which
      includes outpatient oncology practices across the USA. Symptom burden was
      assessed by Patient Care Monitor (PCM) assessments, which are administered as
      part of routine care in a subset of these practices. Eligible patients were women
      diagnosed with breast cancer (ICD-9-CM 174.xx) who developed bone metastases (ICD
      9-CM 198.5) and had >=1 PCM assessment between January 2007 and December 2012.
      The pre-specified endpoint was the occurrence of moderate to severe symptom
      burden, defined as PCM score >=4 (0-10 scale). RESULTS: One thousand one hundred
      five women (median age, 61) met the eligibility criteria. Worsening of symptoms,
      particularly fatigue and pain, occurred in the months leading up to the diagnosis
      of bone metastases. After bone metastases diagnosis, the rate of increase in the
      proportion of patients experiencing moderate/severe symptoms slowed, but
      continued to climb during follow-up. Median time to moderate/severe symptoms was
      0.9 month for fatigue, 1 month for pain, 2.9 months for trouble sleeping, and 7.7
      months for numbness/tingling. Half of the patients received bone-targeted agents
      after diagnosis of bone metastases. CONCLUSIONS: Symptom burden, especially pain
      and fatigue, increased both before and after the diagnosis of bone metastases,
      highlighting the need for proactive monitoring and management of symptoms in
      breast cancer patients.

PMID- 27022967
TI  - Optical Coherence Tomography Angiography Study of Choroidal Neovascularization
      Early Response after Treatment.
AB  - AIMS: Study the choroidal neovascularization (CNV) morphological evolution after
      treatment using optical coherence tomography angiography (OCTA). METHOD: We used
      Optovue XR Avanti, with split-spectrum amplitude-decorrelation angiography
      algorithm. RESULTS: OCT Angiography allows to recognize better the CNV type. In
      our series all our cases seem to follow a 45 to 60 days cycle, after intra
      vitreal injection. After each injection a pruning of smaller vessels is seen
      immediately (after 24 hours) that increases for 6 to 12 days when it reaches a
      maximum. It is followed by a reopening or new sprouting of the vessels 20 to 50
      days later. The later cycles seem longer. Our results on early CNV evolution seem
      to confirm previous observations of CNV abnormalization and arterialization.
      Pruning the small peripheral branches seems to strengthen the trunk. In OCTA,
      closing terminal vessels (anti-VEGF effects) seems to cause an increased flow in
      trunk after the CNV reactivation.

PMID- 27022968
TI  - Response to the Letter to the Editor for "Pharmacotherapy for the Treatment of
      Weight Recidivism or Weight-Loss Plateau Post-Bariatric Surgery".

PMID- 27022966
TI  - Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin
      Gene-Related Peptide.
AB  - The nervous and immune systems communicate bidirectionally, utilizing diverse
      molecular signals including cytokines and neurotransmitters to provide an
      integrated response to changes in the body's internal and external environment.
      Although, neuro-immune interactions are becoming better understood under
      inflammatory circumstances and it has been evidenced that interaction between
      neurons and T cells results in the conversion of encephalitogenic T cells to T
      regulatory cells, relatively little is known about the communication between
      neurons and naive T cells. Here, we demonstrate that following co-culture of
      naive CD4+ T cells with superior cervical ganglion neurons, the percentage of
      Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in
      part by immune-regulatory cytokines TGF-beta and IL-10, as well as the
      neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide
      was shown to play no role in generation of T regulatory cells. Additionally, T
      cells co-cultured with neurons showed a decrease in the levels of pro
      inflammatory cytokine IFN-gamma released upon in vitro stimulation. These
      findings suggest that the generation of Tregs may be promoted by naive CD4+ T
      cell: neuron interaction through the release of neuropeptide CGRP. 

PMID- 27022969
TI  - Pragmatic Trials for Noncommunicable Diseases: Relieving Constraints.
AB  - In this month's editorial, PLOS Medicine Editorial Board member Anushka Patel and
      Ruth Webster discuss how applying rules for drug efficacy trials can impede
      pragmatic trials of interventions for noncommunicable diseases. 

PMID- 27022970
TI  - Ecotoxicological Perspectives of Sex Determination.
AB  - Sex determination or the commitment of the embryo to its sexual fate is a
      fundamental developmental process with paramount consequences in ecology and
      evolution. This process, whether triggered by environmental factors or genotypic
      constitution, can be derailed by environmental contaminants that alter the
      endocrine system, which is a key component of the regulatory network underlying
      vertebrate sex determination. Here, we review the molecular basis of sex
      determination, the endocrine components of its regulation, the maternal and
      endogenous sources of hormones to the developing embryo, and the routes through
      which endocrine disrupting chemicals (EDCs) affect gonadal development in
      reptiles, especially turtles. Among EDCs, we focus on PCBs, BPA, pesticides like
      atrazine, nitrates, and heavy metals. We also consider whether adaptation might
      be possible in the face of persistent chemical insult and conclude that, while
      plausible, contemporary environmental change may outpace adaptive evolution,
      particularly for many species that are already endangered and suffer from small
      population sizes.

PMID- 27022971
TI  - Unusual Phase Transition Behavior of Poly(N-isopropylacrylamide)-co
      Poly(tetrabutylphosphonium styrenesulfonate) in Water: Mild and Linear Changes in
      the Poly(N-isopropylacrylamide) Part.
AB  - In this paper, one LCST-type thermoresponsive poly(ionic liquid) (PIL),
      poly(tetrabutylphosphonium styrenesulfonate) (P[P4,4,4,4][SS]), was introduced to
      poly(N-isopropylacrylamide) (PNIPAM) by two different ways, mixing and
      copolymerization. Interestingly, they show distinct thermoresponsive phase
      transition behaviors, evidenced by temperature-variable (1)H nuclear magnetic
      resonance and Fourier transform infrared in combination with the perturbation
      correlation moving window (PCMW) technique. The PNIPAM/P[P4,4,4,4][SS] mixture
      exhibits a sharp and drastic phase transition, similar to that of pure PNIPAM. In
      the statistical copolymer, PNIPAM-co-P[P4,4,4,4][SS], the thermosensitivity of
      P[P4,4,4,4][SS] is largely suppressed, resulting in a linear, mild, and
      incomplete phase transition, which has never been reported before. This abnormal
      phenomenon is shown to arise from the outstanding hydration ability of
      P[P4,4,4,4][SS]. Our findings should be conducive to improving our understanding
      of the interaction between LCST-type polymers with distinct structures and
      provide a new perspective for preparing thermoresponsive materials with linear
      phase transition behavior. 

PMID- 27022973
TI  - Acoustic behavior associated with cooperative task success in bottlenose dolphins
      (Tursiops truncatus).
AB  - Although many species have proven capable of cooperating to achieve common goals,
      the role of communication in cooperation has received relatively little
      attention. Analysis of communication between partners is vital in determining
      whether actions are truly cooperative rather than serendipitous or learned via
      trial and error (Chalmeau and Gallo in Behav Process 35:101-111, 1996a. doi:
      10.1016/0376-6357(95)00049-6 , Primates 37:39-47, 1996b. doi: 10.1007/BF02382918
      ). Wild cetaceans often produce sounds during cooperative foraging, playing, and
      mating, but the role of these sounds in cooperative events is largely unknown.
      Here, we investigated acoustic communication between two male bottlenose dolphins
      while they cooperatively opened a container (Kuczaj et al. in Anim Cogn 18:543
      550, 2015b. doi: 10.1007/s10071-014-0822-4 ). Analyses of whistles, burst pulses,
      and bi-phonations that occurred during four contexts (i.e., no container, no
      animals interacting with container, one animal interacting with container, and
      two animals interacting with container) revealed that overall sound production
      rate significantly increased during container interactions. Sound production
      rates were also significantly higher during cooperative successes than solo
      successes, suggesting that the coordination of efforts rather than the apparatus
      itself was responsible for the phonation increase. The most common sound type
      during cooperative successes was burst pulse signals, similar to past recordings
      of cooperative events in bottlenose dolphins (Bastian in Animal sonar systems.
      Laboratoire de Physiologie Acoustique, Jouy-en Josas, pp 803-873, 1967; Connor
      and Smolker 1996).

PMID- 27022972
TI  - Selection of Reference Genes for Gene Expression Normalization in Peucedanum
      praeruptorum Dunn under Abiotic Stresses, Hormone Treatments and Different
      Tissues.
AB  - Peucedanum praeruptorum Dunn is one of the main traditional Chinese medicines
      producing coumarins and plenty of literatures are focused on the biosynthesis of
      coumarins. Quantitative real-time reverse transcription PCR (qRT-PCR) is a widely
      used method in studying the biosynthesis pathway and the selection of reference
      genes plays a crucial role in accurate normalization. To facilitate biosynthesis
      study of coumarins, twelve candidate reference genes were selected from the
      transcriptome database of P. praeruptorum according to previous studies. Then,
      BestKeeper, geNoFrm and NormFinder were used for selecting stably expressed
      reference genes in different tissues and under various stress treatments. The
      results indicated that, among the twelve candidate reference genes, the SAND
      family protein (SAND), actin 2 (ACT2), ubiquitin-conjugating enzyme 9 (UBC9),
      protein phosphatase 2A gene (PP2A) and polypyrimidine tract-binding protein
      (PTBP1) were the most stable reference genes under different experimental
      treatments, while glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and tubulin
      beta-6 (TUB6) were the least stable genes. In addition, the suitability of SAND,
      TIP41-like protein (TIP41), UBC9, ACT2, TUB6 and their combination as reference
      genes were confirmed by normalizing the expression of 1-aminocyclopropane-1
      carboxylate oxidase (ACO) in different treatments. This work is the first survey
      of the stability of reference genes in P. praeruptorum and provides guidelines to
      obtain more accurate qRT-PCR results in P. praeruptorum and other plant species. 

PMID- 27022974
TI  - The Critical Role of Substrate in Stabilizing Phosphorene Nanoflake: A
      Theoretical Exploration.
AB  - Phosphorene, a new two-dimensional (2D) semiconductor, has received much interest
      due to its robust direct band gap and high charge mobility. Currently, however,
      phosphorene can only be produced by mechanical or liquid exfoliation, and it is
      still a significant challenge to directly epitaxially grow phosphorene, which
      greatly hinders its mass production and, thus, applications. In epitaxial growth,
      the stability of nanoscale cluster or flake on a substrate is crucial. Here, we
      perform ab initio energy optimizations and molecular dynamics simulations to
      explore the critical role of substrate on the stability of a representative
      phosphorene flake. Our calculations show that the stability of the phosphorene
      nanoflake is strongly dependent on the interaction strength between the nanoflake
      and substrate. Specifically, the strong interaction (0.75 eV/P atom) with Cu(111)
      substrate breaks up the phosphorene nanoflake, while the weak interaction (0.063
      eV/P atom) with h-BN substrate fails to stabilize its 2D structure. Remarkably,
      we find that a substrate with a moderate interaction (about 0.35 eV/P atom) is
      able to stabilize the 2D characteristics of the nanoflake on a realistic time
      scale. Our findings here provide useful guidelines for searching suitable
      substrates for the directly epitaxial growth of phosphorene. 

PMID- 27022976
TI  - High-Performance Phototransistors Based on PDIF-CN2 Solution-Processed Single
      Fiber and Multifiber Assembly.
AB  - Here we describe the fabrication of organic phototransistors based on either
      single or multifibers integrated in three-terminal devices. These self-assembled
      fibers have been produced by solvent-induced precipitation of an air stable and
      solution-processable perylene di-imide derivative, i.e., PDIF-CN2. The
      optoelectronic properties of these devices were compared to devices incorporating
      more disordered spin-coated PDIF-CN2 thin-films. The single-fiber devices
      revealed significantly higher field-effect mobilities, compared to multifiber and
      thin-films, exceeding 2 cm(2) V(-1) s(-1). Such an efficient charge transport is
      the result of strong intermolecular coupling between closely packed PDIF-CN2
      molecules and of a low density of structural defects. The improved crystallinity
      allows efficient collection of photogenerated Frenkel excitons, which results in
      the highest reported responsivity (R) for single-fiber PDI-based
      phototransistors, and photosensitivity (P) exceeding 2 * 10(3) AW(-1), and 5 *
      10(3), respectively. These findings provide unambiguous evidence for the key role
      played by the high degree of order at the supramolecular level to leverage the
      material's properties toward the fabrication of light-sensitive organic field
      effect transistors combining a good operational stability, high responsivity and
      photosensitivity. Our results show also that the air-stability performances are
      superior in devices where highly crystalline supramolecularly engineered
      architectures serve as the active layer. 

PMID- 27022977
TI  - Impact to Underground Sources of Drinking Water and Domestic Wells from
      Production Well Stimulation and Completion Practices in the Pavillion, Wyoming,
      Field.
AB  - A comprehensive analysis of all publicly available data and reports was conducted
      to evaluate impact to Underground Sources of Drinking Water (USDWs) as a result
      of acid stimulation and hydraulic fracturing in the Pavillion, WY, Field.
      Although injection of stimulation fluids into USDWs in the Pavillion Field was
      documented by EPA, potential impact to USDWs at the depths of stimulation as a
      result of this activity was not previously evaluated. Concentrations of major
      ions in produced water samples outside expected levels in the Wind River
      Formation, leakoff of stimulation fluids into formation media, and likely loss of
      zonal isolation during stimulation at several production wells, indicates that
      impact to USDWs has occurred. Detection of organic compounds used for well
      stimulation in samples from two monitoring wells installed by EPA, plus anomalies
      in major ion concentrations in water from one of these monitoring wells, provide
      additional evidence of impact to USDWs and indicate upward solute migration to
      depths of current groundwater use. Detections of diesel range organics and other
      organic compounds in domestic wells <600 m from unlined pits used prior to the
      mid-1990s to dispose diesel-fuel based drilling mud and production fluids suggest
      impact to domestic wells as a result of legacy pit disposal practices.

PMID- 27022978
TI  - Correction: Intrahepatic Transcriptional Signature Associated with Response to
      Interferon-alpha Treatment in the Woodchuck Model of Chronic Hepatitis B.

PMID- 27022975
TI  - The Roles of MDM2 and MDMX in Cancer.
AB  - For more than 25 years, MDM2 and its homolog MDMX (also known as MDM4) have been
      shown to exert oncogenic activity. These two proteins are best understood as
      negative regulators of the p53 tumor suppressor, although they may have
      additional p53-independent roles. Understanding the dysregulation of MDM2 and
      MDMX in human cancers and how they function either together or separately in
      tumorigenesis may improve methods of diagnosis and for assessing prognosis.
      Targeting the proteins themselves, or their regulators, may be a promising
      therapeutic approach to treating some forms of cancer.

PMID- 27022979
TI  - Interpenetrated Si-HPMC/alginate hydrogels as a potential scaffold for human
      tissue regeneration.
AB  - Interpenetrated gels of biocompatible polysaccharides alginate and silanized
      hydroxypropyl methyl cellulose (Si-HPMC) have been studied in order to assess
      their potential as scaffolds for the regeneration of human tissues. Si-HPMC
      networks were formed by reduction of the pH to neutral and alginate networks were
      formed by progressive in situ release of Ca(2+). Linear and non-linear mechanical
      properties of the mixed gels at different polymer and calcium concentrations were
      compared with those of the corresponding single gels. The alginate/Si-HPMC gels
      were found to be stiffer than pure Si-HPMC gels, but weaker and more deformable
      than pure alginate gels. No significant difference was found for the maximum
      stress at rupture measured during compression for all these gels. The degrees of
      swelling or contraction in excess water at pH 7 as well as the release of Ca(2+)
      was measured as a function of time. Pure alginate gels contracted by as much as
      50 % and showed syneresis, which was much reduced or even eliminated for mixed
      gels. The important release of Ca(2+) upon ageing for pure alginate gels was much
      reduced for the mixed gels. Furthermore, results of cytocompatibility assays
      indicated that there was no cytotoxicity of Si-HPMC/alginate hydrogels in 2D and
      3D culture of human SW1353 cells. The results show that using interpenetrated Si
      HPMC/alginate gels has clear advantages over the use of single gels for
      application in tissue regeneration.

PMID- 27022980
TI  - Special issue on "recent advances in meiotic chromosome structure, recombination
      and segregation".

PMID- 27022982
TI  - A Rose by Any Other Name.

PMID- 27022981
TI  - Adjuvants to mechanical ventilation for acute respiratory distress syndrome.

PMID- 27022983
TI  - Precipitation of sword bean proteins by heating and addition of magnesium
      chloride in a crude extract.
AB  - Sword bean (Canavalia gladiata) seeds are a traditional food in Asian countries.
      In this study, we aimed to determine the optimal methods for the precipitation of
      sword bean proteins useful for the food development. The soaking time for sword
      beans was determined by comparing it with that for soybeans. Sword bean proteins
      were extracted from dried seeds in distilled water using novel methods. We found
      that most proteins could be precipitated by heating the extract at more than 90 
      degrees C. Interestingly, adding magnesium chloride to the extract at lower
      temperatures induced specific precipitation of a single protein with a molecular
      weight of approximately 48 kDa. The molecular weight and N-terminal sequence of
      the precipitated protein was identical to that of canavalin. These data suggested
      that canavalin was precipitated by the addition of magnesium chloride to the
      extract. Our results provide important insights into the production of processed
      foods from sword bean. 

PMID- 27022984
TI  - Wounds on Rapanea melanophloeos provide habitat for a large diversity of
      Ophiostomatales including four new species.
AB  - Rapanea melanophloeos, an important canopy tree in Afromontane forests, is
      commonly utilised for medicinal bark harvesting. Wounds created from these
      activities provide entrance for many fungi, including arthropod-associated
      members of the Ophiostomatales and Microascales (ophiostomatoid fungi). In this
      study we assessed the diversity of wound-associated Ophiostomatales on storm
      damaged R. melanophloeos trees in the Afromontane forests of South Africa. Five
      species were identified based on micro-morphological and molecular phylogenetic
      analyses. These included Ophiostoma stenoceras and four newly described taxa
      Sporothrix itsvo sp. nov., S. rapaneae sp. nov., S. uta sp. nov. and O. noisomeae
      sp. nov. Four of these are members of the S. schenckii-O. stenoceras complex (O.
      stenoceras, S. itsvo sp. nov., S. rapaneae sp. nov., S. uta sp. nov.) while O.
      noisomeae groups basal in the Ophiostomatales alongside the S. lignivora complex
      and Graphilbum. In addition to other taxa known from this host, the present study
      shows that there is a rich, yet still poorly explored, diversity of
      Ophiostomatales associated with R. melanophloeos in Afromontane forests. More
      taxa are likely to be discovered with increased research effort. These must be
      assessed in terms of pathogenicity towards this ecologically and economically
      important tree. 

PMID- 27022985
TI  - Response to Letter to the Editor from Ackerman MJ, et al.

PMID- 27022986
TI  - Influence of Transiently Increased Nutritional Risk on a Left Ventricle
      Myocardial Mass Assessed by Echocardiography.
AB  - BACKGROUND/AIM: Metabolic derangements due to increased nutritional risk lead to
      catabolism and loss of proteins, muscle tissue and eventually mass of
      parenchymatous organs. The aim of our study was to assess whether transitory
      nutritional risk after heart surgery influences on the left ventricle myocardial
      mass (LVMM), assessed by echocardiography. METHODS: Consecutive sample of
      patients scheduled for cardiovascular rehabilitation, in period 0-3 months after
      surgery. Nutritional risk screening (NRS) was analyzed using the NRS-2002 tool.
      RESULTS: Study sample included 330 patients after heart surgery for ischemic 186
      (56.4%); valvular 91 (27.6%) and valvular plus ischemic 53 (16.1%) heart disease.
      Age was 65.5 +/- 10.6 (range 23-84) and there were more male patients than female
      - 240 (72.7%) and 90 (27.3%), respectively. The percentage of unintentional loss
      of weight was 10.8 +/- 3.4%, in range 0-23.81%, whereas NRS-2002 was 4.4 +/- 1.1.
      LVMM was 218.7 +/- 65.9 g vs. 252.3 +/- 51.7 (p = 0.015); for patients with
      increased nutritional risk and controls, respectively. There was no significant
      correlation of LVMM with NRS-2002, while the percentage of unintentional loss of
      weight displayed only weakly inverse correlation (Rho CC = -0.197; p = 0.007).
      LVMM also correlated significantly with body mass index (Rho CC = 0.247; p <
      0.001) and waist-to-hip ratio (Rho CC = 0.291; p < 0.001). In conclusion, LVMM
      was found to decrease slightly in the period of increased nutritional risk,
      following heart surgery. Changes in LVMM are partially consequences of systemic
      catabolic response, as well as anthropometric changes due to unintentional loss
      of weight.

PMID- 27022988
TI  - Abstracts working symposium 2016 Pharmaceutical Care Network Europe, 19-20
      February 2016, Hillerod, Denmark.

PMID- 27022989
TI  - Optical Coherence Tomography Angiography Using the Optovue Device.
AB  - Optovue AngioVue system technology for optical coherence tomography (OCT)
      angiography is based on the AngioVue Imaging System (Optovue, Inc., Freemont,
      CA), using split-spectrum amplitude-decorrelation angiography (SSADA) algorithm.
      This algorithm was developed to minimize scanning time. It detects motion in
      blood vessel lumen by measuring the variation in reflected OCT signal amplitude
      between consecutive cross-sectional scans. The novelty of SSADA lies in how the
      OCT signal is processed to enhance flow detection and reject axial bulk motion
      noise. Specifically, the algorithm splits the OCT image into different spectral
      bands, thus increasing the number of usable image frames. Each new frame has a
      lower axial resolution that is less susceptible to axial eye motion caused by
      blood pulsation. Optovue AngioVue system technology allows quantitative analysis.
      It provides numerical data about flow area and non-flow area. It can also
      generate a flow density map. These metrics may serve as biomarkers in diagnosis
      and for tracking disease progression or treatment response. Flow area: the
      software will calculate the drawn area and vessel area in mm(2). It allows for
      comparison of all measurements for a given participant. Non-flow area: the
      software shows the non-perfused areas by mouse click selection. Ischemic areas
      will be shown in yellow. These areas may be saved and matched with others in the
      study. Flow density tool is able to measure the percentage of vascular areas on
      en face angiograms. This analysis is based on an ETDRS grid centered on the
      macula as with the thickness map. This tool works both on inner and outer
      vascular plexus.

PMID- 27022987
TI  - Recent Research Examining Links Among Klebsiella pneumoniae from Food, Food
      Animals, and Human Extraintestinal Infections.
AB  - Klebsiella pneumoniae is a colonizer of livestock, a contaminant of retail meats
      and vegetables, and a cause of extraintestinal infections in humans. Antibiotic
      resistant strains of K. pneumoniae are becoming increasingly prevalent among
      hospital and community-acquired infections. Antibiotics are used extensively in
      conventional food-animal production, where they select for antibiotic-resistant
      bacteria. Antibiotic-resistant K. pneumoniae has been isolated from livestock as
      well as from a variety of retail meats, seafood, and vegetables. Furthermore,
      recent phylogenetic analyses suggest close relationships between K. pneumoniae
      from humans and livestock. Therefore, it is essential that we quantify the
      contribution of foodborne K. pneumoniae to antibiotic-resistant human infections.

PMID- 27022991
TI  - Arthritis as a risk factor for carpal tunnel syndrome: a meta-analysis.
AB  - OBJECTIVES: The effects of inflammatory and degenerative arthritis on carpal
      tunnel syndrome (CTS) are not well known. This systematic review and meta
      analysis aimed to assess whether rheumatoid arthritis (RA) and osteoarthritis
      (OA) increase the risk of CTS. METHOD: Literature searches were conducted in
      PubMed, Embase, Web of Science, Scopus, Google Scholar, and ResearchGate until
      January 2015. Twenty-three (five cohort, 10 case control, and eight cross
      sectional) studies qualified for the meta-analyses. A random-effects meta
      analysis was used and heterogeneity and publication bias were assessed. RESULTS:
      Both RA and OA were associated with CTS. Pooled unadjusted odds ratios (ORs) were
      1.91 [95% confidence interval (CI) 1.33-2.75, I(2) = 55.2%, nine studies, n = 10
      688] for arthritis (either inflammatory or degenerative), 2.91 (95% CI 2.33-3.62,
      I(2) = 22.3%, 11 studies, n = 74 730) for RA, and 2.13 (95% CI 1.65-2.76, I(2) =
      39.2%, five studies, n = 20 574) for OA of any joint. Pooled confounder-adjusted
      ORs were 1.96 (95% CI 1.21-3.18, I(2) = 73.1%, six studies, n = 11 542) for
      arthritis, 1.96 (95% CI 1.57-2.44, I(2) = 32.2%, eight studies, n = 72 212) for
      RA, and 1.87 (95% CI 1.64-2.13, I(2) = 0%, two studies, n = 19 480) for OA. There
      was no evidence of publication bias, and excluding cross-sectional studies or
      studies appraised as having a high risk of selection bias did not change the
      magnitude of the associations. CONCLUSIONS: The findings of this systematic
      review and meta-analysis suggest that both RA and OA increase the risk of CTS.
      Further prospective studies on the effect of wrist OA on CTS are needed.

PMID- 27022992
TI  - Rational control of nano-scale metal-catalysts for biomass conversion.
AB  - Nano-scale metal particles have huge potential due to their wide range of diverse
      catalytic applications. Recently, they have found numerous applications in the
      field of biomass conversion. The proposed contribution is aimed at providing a
      brief account of remarkable recent findings and advances in the design of metal
      based nanocatalysts for biomass valorization. We have discussed the rational
      control of the size, shape, composition and surface properties of nano-scale
      metal catalysts. Following that, the interplay between various structural
      parameters and the catalytic properties in the transformation of cellulose,
      chitin, lignin and lipids has been critically discussed. 

PMID- 27022993
TI  - Physical Activity Patterns in University Students: Do They Follow the Public
      Health Guidelines?
AB  - Physical activity is associated with health. The aim of this study was (a) to
      access if Portuguese university students meet the public health recommendations
      for physical activity and (b) the effect of gender and day of the week on daily
      PA levels of university students. This observational cross-sectional study
      involved 126 (73 women) healthy Portuguese university students aged 18-23 years
      old. Participants wore the ActiGraph wGT3X-BT accelerometer for seven consecutive
      days. Number of steps, time spent sedentary and in light, moderate and vigorous
      physical activity were recorded. The two-way MANOVA revealed that gender (p-value
      = 0.001; eta2 = 0.038; minimum effect) and day of the week (p-value = 0.001; eta2
      = 0.174; minimum effect) had significant main effects on the physical activity
      variables. It was shown that during weekdays, male students walked more steps
      (65.14%), spent less time sedentary (6.77%) and in light activities (3.11%) and
      spent more time in moderate (136.67%) and vigorous activity (171.29%) in
      comparison with weekend days (p < 0.05). The descriptive analysis revealed that
      female students walked more steps (51.18%) and spent more time in moderate
      (125.70%) and vigorous (124.16%) activities during weekdays than in weekend days
      (p < 0.05). Women students did not achieve the recommended 10,000 steps/day on
      average during weekdays and weekend days. Only male students achieved this
      recommendation during weekdays. In summary, this study showed a high incidence of
      sedentary time in university students, mainly on weekend days. New strategies
      must be adopted to promote physical activity in this population, focusing on the
      change of sedentary behaviour. 

PMID- 27022994
TI  - Connectivity to the surface determines diversity patterns in subsurface aquifers
      of the Fennoscandian shield.
AB  - Little research has been conducted on microbial diversity deep under the Earth's
      surface. In this study, the microbial communities of three deep terrestrial
      subsurface aquifers were investigated. Temporal community data over 6 years
      revealed that the phylogenetic structure and community dynamics were highly
      dependent on the degree of isolation from the earth surface biomes. The microbial
      community at the shallow site was the most dynamic and was dominated by the
      sulfur-oxidizing genera Sulfurovum or Sulfurimonas at all-time points. The
      microbial community in the meteoric water filled intermediate aquifer (water
      turnover approximately every 5 years) was less variable and was dominated by
      candidate phylum OD1. Metagenomic analysis of this water demonstrated the
      occurrence of key genes for nitrogen and carbon fixation, sulfate reduction,
      sulfide oxidation and fermentation. The deepest water mass (5000 year old waters)
      had the lowest taxon richness and surprisingly contained Cyanobacteria. The high
      relative abundance of phylogenetic groups associated with nitrogen and sulfur
      cycling, as well as fermentation implied that these processes were important in
      these systems. We conclude that the microbial community patterns appear to be
      shaped by the availability of energy and nutrient sources via connectivity to the
      surface or from deep geological processes.

PMID- 27022995
TI  - Challenges in microbial ecology: building predictive understanding of community
      function and dynamics.
AB  - The importance of microbial communities (MCs) cannot be overstated. MCs underpin
      the biogeochemical cycles of the earth's soil, oceans and the atmosphere, and
      perform ecosystem functions that impact plants, animals and humans. Yet our
      ability to predict and manage the function of these highly complex, dynamically
      changing communities is limited. Building predictive models that link MC
      composition to function is a key emerging challenge in microbial ecology. Here,
      we argue that addressing this challenge requires close coordination of
      experimental data collection and method development with mathematical model
      building. We discuss specific examples where model-experiment integration has
      already resulted in important insights into MC function and structure. We also
      highlight key research questions that still demand better integration of
      experiments and models. We argue that such integration is needed to achieve
      significant progress in our understanding of MC dynamics and function, and we
      make specific practical suggestions as to how this could be achieved.

PMID- 27022996
TI  - Differences down-under: alcohol-fueled methanogenesis by archaea present in
      Australian macropodids.
AB  - The Australian macropodids (kangaroos and wallabies) possess a distinctive
      foregut microbiota that contributes to their reduced methane emissions. However,
      methanogenic archaea are present within the macropodid foregut, although there is
      scant understanding of these microbes. Here, an isolate taxonomically assigned to
      the Methanosphaera genus (Methanosphaera sp. WGK6) was recovered from the
      anterior sacciform forestomach contents of a Western grey kangaroo (Macropus
      fuliginosus). Like the human gut isolate Methanosphaera stadtmanae DSMZ 3091(T),
      strain WGK6 is a methylotroph with no capacity for autotrophic growth. In
      contrast, though with the human isolate, strain WGK6 was found to utilize ethanol
      to support growth, but principally as a source of reducing power. Both the WGK6
      and DSMZ 3091(T) genomes are very similar in terms of their size, synteny and G:C
      content. However, the WGK6 genome was found to encode contiguous genes encoding
      putative alcohol and aldehyde dehydrogenases, which are absent from the DSMZ
      3091(T) genome. Interestingly, homologs of these genes are present in the genomes
      for several other members of the Methanobacteriales. In WGK6, these genes are
      cotranscribed under both growth conditions, and we propose the two genes provide
      a plausible explanation for the ability of WGK6 to utilize ethanol for methanol
      reduction to methane. Furthermore, our in vitro studies suggest that ethanol
      supports a greater cell yield per mol of methane formed compared to hydrogen
      dependent growth. Taken together, this expansion in metabolic versatility can
      explain the persistence of these archaea in the kangaroo foregut, and their
      abundance in these 'low-methane-emitting' herbivores.

PMID- 27022997
TI  - Promotion of healthy nutrition among students participating in a school food aid
      program: a randomized trial.
AB  - OBJECTIVES: To evaluate the potential benefits on students' eating habits, of
      incorporating healthy nutrition education as part of a school food aid program.
      METHODS: 146 schools participating in the DIATROFI Program in Greece during the
      2013-2014 school year were randomly allocated to the environmental intervention
      (received a healthy daily meal) and the multicomponent intervention (MI) group
      (in addition to the meal, a healthy nutrition educational program was applied).
      The analysis, based on 3627 pre-post intervention questionnaire pairs, was
      stratified for children (ages 4-11 years) and adolescents (ages 12-18 years).
      RESULTS: Children participating in the MI group displayed 25 % higher odds of
      increasing the weekly consumption of milk/yoghurt and fruits, 61 % higher odds of
      improving BMI from overweight/obese to normal and 2.5 times higher odds of
      improving from underweight to normal. For adolescents in the MI group, the odds
      of increasing the consumption of vegetables were 40 % higher. In both
      intervention groups, approximately one in four overweight/obese adolescents
      reached normal weight. CONCLUSIONS: Educational programs on healthy nutrition
      might be considered worth implementing in the framework of school food aid
      programs.

PMID- 27022998
TI  - Development and Validation of a Quantitative PCR Method for Equid Herpesvirus-2
      Diagnostics in Respiratory Fluids.
AB  - The protocol describes a quantitative RT-PCR method for the detection and
      quantification of EHV-2 in equine respiratory fluids according to the NF U47-600
      norm. After the development and first validation step, two distinct
      characterization steps were performed according to the AFNOR norm: (a)
      characterization of the qRT-PCR assay alone and (b) characterization of the whole
      analytical method. The validation of the whole analytical method included the
      portrayal of all steps between the extraction of nucleic acids and the final PCR
      analysis. Validation of the whole method is very important for virus detection by
      qRT-PCR in order to get an accurate determination of the viral genome load. Since
      the extraction step is the primary source of loss of biological material, it may
      be considered the main source of error of quantification between one protocol and
      another. For this reason, the AFNOR norm NF-U-47-600 recommends including the
      range of plasmid dilution before the extraction step. In addition, the limits of
      quantification depend on the source from which the virus is extracted. Viral
      genome load results, which are expressed in international units (IU), are easier
      to use in order to compare results between different laboratories. This new
      method of characterization of qRT-PCR should facilitate the harmonization of data
      presentation and interpretation between laboratories. 

PMID- 27022999
TI  - Gram Scale Syntheses of (-)-Incarvillateine and Its Analogs. Discovery of Potent
      Analgesics for Neuropathic Pain.
AB  - (-)-Incarvillateine (INCA) is the major antinociceptive component of Incarvillea
      sinensis, which has been used to treat rheumatism and relieve pain in traditional
      Chinese medicine. We have developed a concise and general synthetic approach for
      INCA, which enabled gram-scale asymmetric syntheses of (-)-INCA, (-)
      incarvilline, (-)-isoincarvilline, and six other INCA analogues. The synthesis of
      isoincarvilline was reported for the first time. Three structurally simplified
      analogues of INCA were also synthesized. In vivo screening found that INCA and
      two structurally optimized analogues were efficacious in preventing the acetic
      acid-induced writhing response. Moreover, their analgesic efficacy was
      demonstrated in formalin induced pain model. More importantly, administration of
      20 or 40 mg/kg INCA and two structurally optimized analogues showed strong
      analgesic effects in spared nerve injury (SNI) model, and their effective doses
      were lower than the current gold standard, gabapentin (100 mg/kg in this model).

PMID- 27023000
TI  - Epigenetic Conversion as a Safe and Simple Method to Obtain Insulin-secreting
      Cells from Adult Skin Fibroblasts.
AB  - Regenerative medicine requires new, fully functional cells that are delivered to
      patients in order to repair degenerated or damaged tissues. When such cells are
      not readily available, they can be obtained using different approaches that
      include, among the many, reprogramming and trans-differentiation, with advantages
      and limitations that are specific of the different techniques. Here a new
      strategy for the conversion of an adult mature fibroblast into an insulin
      secreting cell, arbitrarily designated as epigenetic converted cells (EpiCC), is
      described. The method has been developed, based on the increasing understanding
      of the mechanisms controlling epigenetic regulation of cell fate and
      differentiation. In particular, the first step uses an epigenetic modifier,
      namely 5-aza-cytidine, to drive adult cells into a "highly permissive" state. It
      then takes advantage of this brief and reversible window of epigenetic
      plasticity, to re-address cells toward a different lineage. The approach is
      designated "epigenetic cell conversion". It is a simple and robust way to obtain
      an efficient, controlled and stable cellular inter-lineage switch. Since the
      protocol does not involve the use of any gene transfection, it is free of viral
      vectors and does not involve a stable pluripotent state, it is highly promising
      for translational medicine applications. 

PMID- 27023001
TI  - Sialoglycoprotein Isolated from Eggs of Carassius auratus Ameliorates
      Osteoporosis: An Effect Associated with Regulation of the Wnt/beta-Catenin
      Pathway in Rodents.
AB  - In the current study, ovariectomized (OVX) rats and the senescence-accelerated
      mouse strain P6 (SAMP6) were employed to establish models of postmenopausal
      osteoporosis and senile osteoporosis, respectively. The effects of treatment with
      sialoglycoprotein isolated from the eggs of Carassius auratus (Ca-SGP) on these
      two types of osteoporosis were investigated in vivo. Results showed that Ca-SGP
      significantly increased bone mineral density, ameliorated trabecular bone
      microstructure, and improved bone biomechanical properties in both OVX rats and
      SAMP6. The osteogenesis related Wnt/beta-catenin pathway was targeted to study
      the underlying mechanism of Ca-SGP activity. In postmenopausal osteoporosis, Ca
      SGP suppressed the activation of Wnt/beta-catenin signal via down-regulating the
      expression of key genes including LRP5, beta-catenin, and Runx2, suggesting that
      overactive osteogenesis was controlled by Ca-SGP. The bone formation was sharply
      weakened in senile osteoporosis, whereas Ca-SGP treatment promoted osteoblast
      activity by stimulating the Wnt/beta-catenin signal. In conclusion, Ca-SGP
      ameliorated these two types of osteoporosis by normalizing bone anabolism. 

PMID- 27023002
TI  - Comparison of Whole-Body (18)F FDG PET/MR Imaging and Whole-Body (18)F FDG PET/CT
      in Terms of Lesion Detection and Radiation Dose in Patients with Breast Cancer.
AB  - Purpose To compare fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron
      emission tomography (PET) and magnetic resonance (MR) imaging with (18)F FDG
      combined PET and computed tomography (CT) in terms of organ-specific metastatic
      lesion detection and radiation dose in patients with breast cancer. Materials and
      Methods From July 2012 to October 2013, this institutional review board-approved
      HIPAA-compliant prospective study included 51 patients with breast cancer (50
      women; mean age, 56 years; range, 32-76 years; one man; aged 70 years) who
      completed PET/MR imaging with diffusion-weighted and contrast material-enhanced
      sequences after unenhanced PET/CT. Written informed consent for study
      participation was obtained. Two independent readers for each modality recorded
      site and number of lesions. Imaging and clinical follow-up, with consensus in two
      cases, served as the reference standard. Results There were 242 distant
      metastatic lesions in 30 patients, 18 breast cancers in 17 patients, and 19
      positive axillary nodes in eight patients. On a per-patient basis, PET/MR imaging
      with diffusion-weighted and contrast-enhanced sequences depicted distant (30 of
      30 [100%] for readers 1 and 2) and axillary (eight of eight [100%] for reader 1,
      seven of eight [88%] for reader 2) metastatic disease at rates similar to those
      of unenhanced PET/CT (distant metastatic disease: 28 of 29 [96%] for readers 3
      and 4, P = .50; axillary metastatic disease: seven of eight [88%] for readers 3
      and 4, P > .99) and outperformed PET/CT in the detection of breast cancer (17 of
      17 [100%] for readers 1 and 2 vs 11 of 17 [65%] for reader 3 and 10 of 17 [59%]
      for reader 4; P < .001). PET/MR imaging showed increased sensitivity for liver
      (40 of 40 [100%] for reader 1 and 32 of 40 [80%] for reader 2 vs 30 of 40 [75%]
      for reader 3 and 28 of 40 [70%] for reader 4; P < .001) and bone (105 of 107
      [98%] for reader 1 and 102 of 107 [95%] for reader 2 vs 106 of 107 [99%] for
      reader 3 and 93 of 107 [87%] for reader 4; P = .012) metastases and revealed
      brain metastases in five of 51 (10%) patients. PET/CT trended toward increased
      sensitivity for lung metastases (20 of 23 [87%] for reader 1 and 17 of 23 [74%]
      for reader 2 vs 23 of 23 [100%] for reader 3 and 22 of 23 [96%] for reader 4; P =
      .065). Dose reduction averaged 50% (P < .001). Conclusion In patients with breast
      cancer, PET/MR imaging may yield better sensitivity for liver and possibly bone
      metastases but not for pulmonary metastases, as compared with that attained with
      PET/CT, at about half the radiation dose. ((c)) RSNA, 2016 Online supplemental
      material is available for this article. 

PMID- 27023003
TI  - Efficacy of Astaxanthin for the Treatment of Atopic Dermatitis in a Murine Model.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory skin disease associated
      with various factors, including immunological abnormalities and exposure to
      allergens. Astaxanthin (AST) is a xanthophyll carotenoid that has recently been
      demonstrated to have anti-inflammatory effects and to regulate the expression of
      inflammatory cytokines. Thus, we investigated whether AST could improve the
      dermatitis and pruritus in a murine model of AD using NC/Nga mice. In addition to
      a behavioral evaluation, the effects of AST on the AD were determined by the
      clinical skin severity score, serum IgE level, histological analyses of skin, and
      by reverse transcription-PCR and Western blotting analyses for the expression of
      inflammation-related factors. AST (100 mg/kg) or vehicle (olive oil) was orally
      administered once day and three times a week for 26 days. When compared with
      vehicle-treated group, the administration of AST significantly reduced the
      clinical skin severity score. In addition, the spontaneous scratching in AD model
      mice was reduced by AST administration. Moreover, the serum IgE level was
      markedly decreased by the oral administration of AST compared to that in vehicle
      treated mice. The number of eosinophils, total and degranulated mast cells all
      significantly decreased in the skin of AST-treated mice compared with vehicle
      treated mice. The mRNA and protein levels of eotaxin, MIF, IL-4, IL-5 and L
      histidine decarboxylase were significantly decreased in the skin of AST-treated
      mice compared with vehicle-treated mice. These results suggest that AST improves
      the dermatitis and pruritus in AD via the regulation of the inflammatory effects
      and the expression of inflammatory cytokines. 

PMID- 27023004
TI  - Prevalence of musculoskeletal disorders and rheumatic diseases in Cuenca,
      Ecuador: a WHO-ILAR COPCORD study.
AB  - The aim of this study was to determine the prevalence of musculoskeletal pain and
      rheumatic diseases in subjects over 18 years of age from the canton of Cuenca,
      Ecuador. Cross-sectional analytical community-based study was conducted in
      subjects over 18 years of age using the validated Community-Oriented Program for
      the Control of Rheumatic Diseases (COPCORD) questionnaire. Random sampling was
      used. The questionnaire was administered by standardized health workers. Subjects
      were visited house by house. Subjects positive for musculoskeletal (MSK) pain in
      the last 7 days and at some point in life were assessed by rheumatologists to
      confirm the diagnosis. A total of 4877 subjects participated, with an average age
      of 42.8 (SD 18.8) years of age; 59.7 % were women; 69.7 % lived in urban areas.
      32.5 % reported MSK pain in the last 7 days and 45.7 % at some point in life. The
      prevalence of knee osteoarthritis was 7.4 %, hand osteoarthritis 5.3 %, low back
      pain 9.3 %, rheumatoid arthritis 0.8 %, fibromyalgia 2 %, gout 0.4 %, and lupus
      0.06 %. Subjects from rural areas reported experiencing more MSK pain in the last
      7 days and at some point in life, lower income, poorer health-care coverage, and
      increased physical activity involving repetitive tasks such as lifting weights or
      cooking with firewood. MSK pain prevalence was high. Osteoarthritis and low back
      pain were the most common diseases. Age, sex, physical activity, repetitive
      tasks, living in a rural area, and lack of health-care coverage were found to be
      associated with MSK pain. 

PMID- 27023005
TI  - Intimate Partner Violence Is Associated with Stress-Related Sleep Disturbance and
      Poor Sleep Quality during Early Pregnancy.
AB  - OBJECTIVES: To examine the associations of Intimate partner violence (IPV) with
      stress-related sleep disturbance (measured using the Ford Insomnia Response to
      Stress Test [FIRST]) and poor sleep quality (measured using the Pittsburgh Sleep
      Quality Index [PSQI]) during early pregnancy. METHODS: This cross-sectional study
      included 634 pregnant Peruvian women. In-person interviews were conducted in
      early pregnancy to collect information regarding IPV history, and sleep traits.
      Adjusted odds ratios (aOR) and 95% confidence intervals (95%CIs) were calculated
      using logistic regression procedures. RESULTS: Lifetime IPV was associated with a
      1.54-fold increased odds of stress-related sleep disturbance (95% CI: 1.08-2.17)
      and a 1.93-fold increased odds of poor sleep quality (95% CI: 1.33-2.81).
      Compared with women experiencing no IPV during lifetime, the aOR (95% CI) for
      stress-related sleep disturbance associated with each type of IPV were: physical
      abuse only 1.24 (95% CI: 0.84-1.83), sexual abuse only 3.44 (95%CI: 1.07-11.05),
      and physical and sexual abuse 2.51 (95% CI: 1.27-4.96). The corresponding aORs
      (95% CI) for poor sleep quality were: 1.72 (95% CI: 1.13-2.61), 2.82 (95% CI:
      0.99-8.03), and 2.50 (95% CI: 1.30-4.81), respectively. Women reporting any IPV
      in the year prior to pregnancy had increased odds of stress-related sleep
      disturbance (aOR = 2.07; 95% CI: 1.17-3.67) and poor sleep quality (aOR = 2.27;
      95% CI: 1.30-3.97) during pregnancy. CONCLUSION: Lifetime and prevalent IPV
      exposures are associated with stress-related sleep disturbance and poor sleep
      quality during pregnancy. Our findings suggest that sleep disturbances may be
      important mechanisms that underlie the lasting adverse effects of IPV on maternal
      and perinatal health.

PMID- 27023007
TI  - Predictions Burden of Diabetes and Economics Cost: Contributing Risk Factors of
      Changing Disease Prevalence and its Pandemic Impact to Qatar.
AB  - Background: The Middle East region is predicted to have one of the highest
      prevalence of diabetes mellitus (DM) in the world. The risk of diabetes continues
      to increase worldwide and its public health burden is unevenly distributed across
      socioeconomic strata. This burden is not only related to health care costs, but
      also to indirect costs caused by loss of productivity from disability and
      premature mortality. Aim: This study aims to estimate the economics cost of type
      2 Diabetes Mellitus [T2DM] among adults in Qatar using national data, and to
      quantify the potential effect of a suggested preventive intervention program.
      Design: It is an observational cohort study. Setting: The survey was based on
      registry at the Hamad General Hospital and Primary Health Care (PHC) centers in
      the State of Qatar. Subject: This study consisted of patients above 25 years of
      age with diagnosed diabetes mellitus registered at Hamad General Hospital and
      Primary Health Care (PHC) centers during January 2004 to July 2014. Methods: We
      developed a dynamic model in which actual incidence, prevalence, and life
      expectancy data are used and alternative assumptions about future trends in these
      parameters can be incorporated. Linear regression model has been performed to
      forecast the burden of diabetes in oil-rich country. Results: According to the
      dynamic model, a 10% increased in the number of diabetic patients in the State of
      Qatar from 33 610 in 2005 to 122 000 in 2012 (about 1% annually). The annual
      diabetes incidence rate was higher in women than in men during a period between
      2005 to 2015 years. The static model forecasted as 10% increase over 10 years.
      The relative increase in prevalence of diabetes and number of diabetic people are
      higher in women than in men (16.6%; 17.5% and 18.4% in men vs. 22.6%; 23.8% and
      25.1% in women). Most of the increase in prevalence of diabetes is projected to
      occur in younger age groups where it is estimated to increase among age groups of
      50-59 years and above 60 years, respectively. Conclusion: The burden of diabetes
      in Qatar is markedly larger than proposed by IDF estimations - suggesting that
      Qatar would be one of the top 10 countries worldwide in diabetes prevalence.
      Family history of diabetes, consanguinity marriages', hereditary gene-environment
      interactions, poor nutrition in utero and in early life plus over nutrition in
      later life may also contribute to the current diabetes epidemic in Qatari's Arab
      populations. Finally, continuous training of primary health care professionals on
      diabetes care and prevention is an essential tool of improving diabetes in Qatar.

PMID- 27023006
TI  - Gap Junctions Contribute to the Regulation of Walking-Like Activity in the Adult
      Mudpuppy (Necturus Maculatus).
AB  - Although gap junctions are widely expressed in the developing central nervous
      system, the role of electrical coupling of neurons and glial cells via gap
      junctions in the spinal cord in adults is largely unknown. We investigated
      whether gap junctions are expressed in the mature spinal cord of the mudpuppy and
      tested the effects of applying gap junction blocker on the walking-like activity
      induced by NMDA or glutamate in an in vitro mudpuppy preparation. We found that
      glial and neural cells in the mudpuppy spinal cord expressed different types of
      connexins that include connexin 32 (Cx32), connexin 36 (Cx36), connexin 37
      (Cx37), and connexin 43 (Cx43). Application of a battery of gap junction blockers
      from three different structural classes (carbenexolone, flufenamic acid, and long
      chain alcohols) substantially and consistently altered the locomotor-like
      activity in a dose-dependent manner. In contrast, these blockers did not
      significantly change the amplitude of the dorsal root reflex, indicating that gap
      junction blockers did not inhibit neuronal excitability nonselectively in the
      spinal cord. Taken together, these results suggest that gap junctions play a
      significant modulatory role in the spinal neural networks responsible for the
      generation of walking-like activity in the adult mudpuppy. 

PMID- 27023008
TI  - Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1
      Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial.
AB  - BACKGROUND: Growth hormone (GH) secretion is increased in pre-pubertal children
      with type 1 diabetes and GH excess produces insulin resistance. Early-morning
      insulinopenia contributes to lower insulin-like growth factor (IGF-I) levels and
      to GH hypersecretion. OBJECTIVE: To evaluate differences in GH/IGF-I axis of pre
      pubertal children with type 1 diabetes treated with glargine or detemir as long
      acting insulin analogues, which was the main outcome measure, and to compare
      insulin effects in obtaining good metabolic control. SUBJECTS: Children with type
      1 diabetes. METHODS: This was a 32-week, randomized, open-label, two-period,
      cross-over comparison between bedtime glargine and twice-daily detemir insulin,
      involving pre-pubertal children in care at a diabetes pediatric centre. After a 8
      week-run-in period subjects were randomized to bedtime glargine or twice-daily
      detemir insulin administration. After a 12-week period treatments were inverted
      and continued for additional 12 weeks. RESULTS: Overall, 15 pre-pubertal children
      (53.3% males, mean age 8.6+/-1.5 years, duration of diabetes 4.2+/-1.5 years)
      completed the study. Groups did not differ for GH/IGF axis and HbA1c levels.
      Treatment with glargine was associated with lower fasting glucose values than
      treatment with detemir (8.1+/-1.5 vs. 8.2+/-1.7 mmol/L, p=0.01). Incidence rate
      of hypoglycemia was not different between insulin treatments (IRR=1.18, 95%CI
      1.00-1.38; p=0.07). Detemir treatment was associated with a higher increase in
      body weight (p=0.008) and height (p=0.02) when compared with glargine.
      CONCLUSION: Detemir and glargine not show significant differential effects on the
      GH/IGFI axis. The greater weight gain and height associated with detemir
      treatment, apparently not related to the level of pubertal growth, deserve
      further investigation.

PMID- 27023009
TI  - Subcutaneous Administration of Otelixizumab is Limited by Injection Site
      Reactions: Results of an Exploratory Study in Type 1 Diabetes Mellitus Patients.
AB  - Targeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been
      shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes
      mellitus patients. However, effective doses are associated with infusion
      reactions typical of "cytokine release syndrome" and appear to be dose-limiting
      when administered as short-duration infusions. A possible alternative approach,
      which may reduce the rate of T cell activation and consequent systemic cytokine
      release, is to inject subcutaneously. We investigated single- and repeat-dose
      subcutaneous administration of the anti-CD3 monoclonal antibody otelixizumab in
      small cohorts of patients with type 1 diabetes. Transient reductions in free or
      unbound CD3 antigen on CD4+ and CD8+ cells and absolute lymphocyte count were
      observed in the blood of these patients during treatment, consistent with the
      known mechanism of action of otelixizumab and other anti-CD3 monoclonal
      antibodies. This was despite the very low systemic exposure of antibodies
      measured during the same time period. With the exception of sporadic headaches,
      other symptoms associated with cytokine release syndrome, such as fever, nausea,
      vomiting, myalgia, and arthralgia, were absent in treated patients. However,
      treatment-related injection site reactions were consistently observed. The
      reactions were erythematous and their sizes were dose-dependent; in some cases,
      reactions persisted for up to 2 weeks following the start of treatment. While
      patients responded well to topical corticosteroid treatment and prophylaxis
      reduced the intensity of injection site reactions, the reactions were considered
      dose-limiting and higher doses were not investigated. 

PMID- 27023010
TI  - Calibrated Passive Sampling--Multi-plot Field Measurements of NH3 Emissions with
      a Combination of Dynamic Tube Method and Passive Samplers.
AB  - Agricultural ammonia (NH3) emissions (90% of total EU emissions) are responsible
      for about 45% airborne eutrophication, 31% soil acidification and 12% fine dust
      formation within the EU15. But NH3 emissions also mean a considerable loss of
      nutrients. Many studies on NH3 emission from organic and mineral fertilizer
      application have been performed in recent decades. Nevertheless, research related
      to NH3 emissions after application fertilizers is still limited in particular
      with respect to relationships to emissions, fertilizer type, site conditions and
      crop growth. Due to the variable response of crops to treatments, effects can
      only be validated in experimental designs including field replication for
      statistical testing. The dominating ammonia loss methods yielding quantitative
      emissions require large field areas, expensive equipment or current supply, which
      restricts their application in replicated field trials. This protocol describes a
      new methodology for the measurement of NH3 emissions on many plots linking a
      simple semi-quantitative measuring method used in all plots, with a quantitative
      method by simultaneous measurements using both methods on selected plots. As a
      semi-quantitative measurement method passive samplers are used. The second method
      is a dynamic chamber method (Dynamic Tube Method) to obtain a transfer quotient,
      which converts the semi-quantitative losses of the passive sampler to
      quantitative losses (kg nitrogen ha(-1)). The principle underlying this approach
      is that passive samplers placed in a homogeneous experimental field have the same
      NH3 absorption behavior under identical environmental conditions. Therefore, a
      transfer co-efficient obtained from single passive samplers can be used to scale
      the values of all passive samplers used in the same field trial. The method
      proved valid under a wide range of experimental conditions and is recommended to
      be used under conditions with bare soil or small canopies (<0.3 m). Results
      obtained from experiments with taller plants should be treated more carefully. 

PMID- 27023011
TI  - LC-MS method development and comparison of sampling materials for the analysis of
      organic gunshot residues.
AB  - This study aimed at developing a LC-MS method to compare the efficiency of
      various sampling materials for the collection and subsequent analysis of organic
      gunshot residues (OGSR). Seven sampling materials, namely two "swab"-type and
      five "stub"-type collection materials, were tested. The evaluation of sampling
      materials was systematically carried out by first analyzing blank extracts of the
      materials to check for potential interferences and determining matrix effects.
      Based on these results, the best four materials, namely cotton buds, polyester
      swabs, a tape from 3M and PTFE were compared in terms of collection efficiency
      during shooting experiments using a set of 9mm Luger ammunition. It was found
      that the tape was capable of recovering the highest amounts of OGSR. As tape
      lifting is the technique currently used in routine for inorganic GSR, OGSR
      analysis might be implemented without modifying IGSR sampling and analysis
      procedure.

PMID- 27023012
TI  - Long-term Results of Troublesome CWD Cavity Reconstruction by Mastoid and
      Epitympanic Bony Obliteration (CWR-BOT) in Adults.
AB  - OBJECTIVE: To present the long-term surgical outcome of the bony mastoid and
      epitympanic obliteration technique with canal wall reconstruction (CWR-BOT) in
      adults with an unstable cavity after previous canal wall-down surgery for
      extensive cholesteatoma. STUDY DESIGN: Retrospective study. INTERVENTIONS:
      Therapeutic. SETTING: Tertiary referral center. PATIENTS: Fifty consecutive adult
      patients undergoing a CWR-BOT between 1998 and 2009. MAIN OUTCOME MEASURE(S): (A)
      Recurrence and residual rates of cholesteatoma, (B) postoperative hygienic status
      of the ear, including postoperative aspect of the tympanic membrane and external
      ear canal integrity (EAC), (C) functional outcome, and (D) long-term safety
      issues. RESULTS: (A) The percentage of ears remaining safe without recurrent or
      residual disease after CWR-BOT was 96% after a mean follow-up time of 101.8
      months. Recurrent cholesteatoma occurred in 2% (n = 1) and a residual
      cholesteatoma was detected in 2% (n = 1) of the patients. (B) A safe dry, and
      trouble-free graft and selfcleaning EAC was achieved in 94%. (C) The
      postoperative hearing results showed a gain of 1.7 dB on pure-tone average air
      conduction. (D) Nonecho planar diffusion-weighted imaging (non-EP DW magnetic
      resonance imaging) documented the residual (n = 1) and recurrent cholesteatoma (n
      = 1). The 1- and 5-year imaging follow-up revealed no other recurrent or residual
      disease. CONCLUSION: The CWR-BOT is a safe and very effective option for
      treatment of problematic unstable canal wall-down mastoid cavities, resulting in
      dry trouble-free ears.

PMID- 27023013
TI  - Acoustic Properties of Collagenous Matrices of Xenogenic Origin for Tympanic
      Membrane Reconstruction.
AB  - HYPOTHESIS: The acoustic properties of scaffolds made from decellularized
      extracellular cartilage matrices of porcine origin are comparable to those of the
      human tympanic membrane. BACKGROUND: Currently, the reconstruction of tympanic
      membrane in the context of chronic tympanic membrane defects is mostly performed
      using autologous fascia or cartilage. Autologous tissue may be associated with
      lack of graft material in revision patients and requires more invasive and longer
      operative time. Therefore, other materials are investigated for reconstruction.
      An increasingly important role could be played by scaffolds from different
      materials, which are known to induce constructive tissue remodeling. METHODS: To
      analyze the acoustic properties, the vibrations of the scaffolds, cartilage,
      perichondrium and tympanic membrane were measured by laser scanning doppler
      vibrometry under different static pressures. RESULTS: The analysis of volume
      velocities serves as an indicator for sound transmission. The results of the
      average volume velocities at atmospheric pressure show a similar frequency
      response of the tympanic membrane and the scaffolds with a peak at about 800 Hz.
      After changing the artificial ear-canal pressure from atmospheric pressure to
      negative pressure (-100, -200, and -300 daPa) the vibration characteristics of
      the different membranes remain fairly constant, whereas the results of the
      perichondrium show a decrease after changing the pressure into the negative range
      in the frequencies 1 to 3 kHz. CONCLUSION: The present study showed that the
      vibration characteristics of the scaffolds under atmospheric and negative
      pressure can be interpreted as similar to those of thin cartilage (<0.5 mm) and
      human tympanic membranes. However, in relation to the behavior of these scaffolds
      made from decellularized extracellular cartilage matrices in vivo, further
      investigations should be carried out.

PMID- 27023014
TI  - Microsurgical Anatomy of the Internal Acoustic Meatus as Seen Using the
      Retrosigmoid Approach.
AB  - HYPOTHESIS: To show via a retrosigmoid approach the bony labyrinth anatomy and
      its relationship with the internal acoustic meatus so as to provide guidelines
      for a safer drilling to the fundus using this approach. BACKGROUND: Few studies
      deal with the complex anatomy of petrous bone structures as observed by a
      retrosigmoid approach. METHODS: Ten retrosigmoid approaches were performed
      bilaterally on five fresh cadaveric heads. Afterward high-resolution computed
      tomographic scans were obtained. Measurements of landmarks and distances between
      important topographic structures of the pyramid were obtained on its surface
      using a navigation system. Semicircular canals, vestibular aqueduct, and internal
      acoustic meatus were dissected to show their anatomy and relationships. RESULTS:
      The anatomy of the inner ear structures was shown. Opening of the internal
      acoustic meatus was accomplished without injury to the labyrinth in 9 out of 10
      sides. The distance between the drilled bone of the internal acoustic meatus and
      the vestibule was calculated on the postoperative computed tomographic scan. The
      mean value was 1.43 mm (SD, 0.30 mm; range, 1.0-1.8 mm). CONCLUSION: A better
      knowledge of the anatomy of the semicircular canals and of the vestibular
      aqueduct as observed by a retrosigmoid approach, together with their
      relationships to the fundus and other petrous bone landmarks, can be useful to
      get a general orientation in acoustic neuroma surgery. Using this information
      together with the neuronavigation, we were able to successfully open the internal
      acoustic meatus without entering labyrinthine structures in 90% of the study
      dissections.

PMID- 27023015
TI  - Objectification and Differential Diagnosis of Vascular Pulsatile Tinnitus by
      Transcanal Sound Recording and Spectrotemporal Analysis: A Preliminary Study.
AB  - OBJECTIVE: Although frequently classified as "objective tinnitus," in most cases
      vascular pulsatile tinnitus (VPT) is not equal to objective tinnitus because it
      is not easy to objectively document VPT. The present study was conducted to
      develop a novel transcanal sound recording and spectrotemporal analysis method
      for the objective and differential diagnosis of VPT. STUDY DESIGN: A case series
      with a control group. SETTING: Tertiary referral center. PATIENTS: Six VPT
      subjects with radiological abnormalities and six normal controls. INTERVENTIONS
      AND MAIN OUTCOME MEASURE: The method was tested based on recordings obtained from
      the ipsilateral external auditory canal (EAC) using an insert microphone with the
      subject's head in four different positions. The recorded signals were first
      analyzed in the time domain, and short-time Fourier transform was performed to
      analyze the data in the time-frequency domain. RESULTS: From the temporal
      analysis, the ear canal signals recorded from the VPT subjects exhibited large
      peak amplitudes and periodic structures, whereas the signals recorded from the
      control subjects had smaller peak amplitudes and weaker periodicity. From the STA
      represented by two-dimensional spectrograms and three-dimensional waterfall
      diagrams, all of the VPT subjects demonstrated pulse-synchronous acoustic
      characteristics that were representative of their respective presumptive vascular
      pathologies, whereas the control subjects did not display such characteristics.
      CONCLUSION: The present diagnostic approach may provide additional information
      regarding the origins of VPT cases as well as an efficient and objective
      diagnostic method. Furthermore, this approach may aid in the determination of
      appropriate imaging modalities, treatment planning, and evaluation of treatment
      outcomes.

PMID- 27023016
TI  - Active Middle Ear Implantation: Long-term Medical and Technical Follow-up,
      Implant Survival, and Complications.
AB  - OBJECTIVE: To evaluate the long-term medical and technical results, implant
      survival, and complications of the semi-implantable vibrant soundbridge (VSB),
      otologics middle ear transducer (MET), and the otologics fully implantable
      ossicular stimulator (FIMOS). STUDY DESIGN: Retrospective cohort study. PATIENTS:
      Patients with chronic external otitis and either moderate to severe sensorineural
      or conductive/mixed hearing loss. SETTING: Tertiary referral center.
      INTERVENTION: Implantation with the VSB, MET, or FIMOS. MAIN OUTCOME MEASURES:
      Medical complications, number of reimplantations, and explantations. RESULTS:
      Ninety-four patients were implanted, 12 patients with a round window or stapes
      application. 28 patients were lost to follow-up. The average follow-up duration
      was 4.4 years (range, 1 month-15 years). 128 devices were evaluated: (92 VSB, 32
      MET, 4 FIMOS). 36 devices (28%) have been explanted or replaced (18 VSB, 14 MET,
      4 FIMOS). Device failure was 7% for VSB, 28% for MET, and 100% for FIMOS. In 16
      patients (17%) revision surgery (n = 20) was performed. Twenty patients (21%)
      suffered any medical complication. CONCLUSION: Medical and technical
      complications and device failures have mostly occurred in the initial period of
      active middle ear implants (AMEI) implementation and during clinical trials or
      experimental procedures. All four FIMOS had technical difficulties. An important
      decrease in the occurrence of both medical and technical complications was
      observed. Application in more recent years did not show any complications and the
      recent device failure rates are acceptable. Magnetic resonance imaging (MRI)
      incompatibility should be taken into account when indicating AMEI.

PMID- 27023017
TI  - Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick
      (>4 mm) cutaneous melanoma: an observational study.
AB  - BACKGROUND: The role of sentinel lymph node biopsy and the benefit of
      immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain.
      OBJECTIVES: Our aim was to assess the value of both sentinel lymph node (SLN)
      biopsy and immunotherapy in the prognosis of thick melanomas. METHODS: A
      retrospective study based on a computerized patient database in which patients
      have been prospectively collected since 2005 was performed. Age, sex, location,
      Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating
      lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were
      included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall
      (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression
      analysis. RESULTS: A series of 141 patients with melanomas thicker than 4 mm were
      included. Multivariate regression showed a worse prognosis in SLN-positive
      patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2,
      p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group
      was shown to have a worse prognosis than the SLN-positive group but was very
      similar to the clinically positive group. Immunotherapy with high-dose interferon
      showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR
      0.3, p = 0.001). CONCLUSION: Our data indicate that SLN biopsy and adjuvant
      interferon should be considered for patients with thick melanomas.

PMID- 27023018
TI  - Are retinoid/antibiotic fixed-dose combination acne treatments associated with
      antibiotic resistance?

PMID- 27023019
TI  - Residents'corner January/February 2016. Editorial: What's new this month?

PMID- 27023020
TI  - Salinity-dependent Toxicity Assay of Silver Nanocolloids Using Medaka Eggs.
AB  - Salinity is an important characteristic of the aquatic environment. For aquatic
      organisms it defines the habitats of freshwater, brackish water, and seawater.
      Tests of the toxicity of chemicals and assessments of their ecological risks to
      aquatic organisms are frequently performed in freshwater, but the toxicity of
      chemicals to aquatic organisms depends on pH, temperature, and salinity. There is
      no method, however, for testing the salinity dependence of toxicity to aquatic
      organisms. Here, we used medaka (Oryzias latipes) because they can adapt to
      freshwater, brackish water, and seawater. Different concentrations of embryo
      rearing medium (ERM) (1x, 5x, 10x, 15x, 20x, and 30x) were employed to test the
      toxicity of silver nanocolloidal particles (SNCs) to medaka eggs (1x ERM and 30x
      ERM have osmotic pressures equivalent to freshwater and seawater, respectively).
      In six-well plastic plates, 15 medaka eggs in triplicate were exposed to SNCs at
      10 mg/L(-1) in different concentrations of ERM at pH 7 and 25  degrees C in the
      dark. We used a dissecting microscope and a micrometer to measure heart rate per
      15 sec and eye diameter on day 6 and full body length of the larvae on hatching
      day (section 4). The embryos were observed until hatching or day 14; we then
      counted the hatching rate every day for 14 days (section 4). To see silver
      accumulation in embryos, we used inductively coupled plasma mass spectrometry to
      measure the silver concentration of test solutions (section 5) and dechorionated
      embryos (section 6).The toxicity of the SNCs to medaka embryos obviously
      increased with increasing salinity. This new method allows us to test the
      toxicity of chemicals in different salinities. 

PMID- 27023021
TI  - Understanding vaccination rates and attitudes among patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: Appropriate vaccinations are important for patients with rheumatoid
      arthritis (RA), who are often treated with highly immunosuppressive therapies
      that increase their risk of infection. However, rates of vaccination among
      patients with RA are below optimal levels. STUDY DESIGN: We conducted a patient
      survey to assess self-reported vaccination status and to compare that status with
      electronic health record (EHR) data. METHODS: We recruited randomly selected
      patients with RA in an academic practice in 2013. Eligible participants had a
      diagnosis of RA, at least 1 visit to a rheumatology clinic in each of the
      previous 2 years, were 18 years or older, and had English listed as their
      preferred language. The survey included the following domains: a) patient self
      reported receipt of influenza, pneumococcal (PNVX), and herpes zoster (HZVX)
      vaccinations; b) attitudes about these vaccines, including reasons for
      unvaccinated status, if applicable; and c) provider recommendations about these
      vaccines. RESULTS: Based on participants' self-report, we found a high
      vaccination rate for influenza during the previous season (79.4%), a moderate
      rate of any previous vaccination for pneumococcus (53.9%), and a very low rate of
      any previous vaccination for herpes zoster (7.8%). If we assume that all self
      reports are accurate and we include vaccinations recorded in the EHR that were
      not reported by patients, the vaccination rates were approximately 8% to 9%
      higher for PNVX and HZVX. CONCLUSIONS: Vaccination rates are low among patients
      with RA based on self-report data. Further research is needed to investigate
      system-level barriers to vaccination and the impact of evidence-based, provider
      level interventions on vaccination rates.

PMID- 27023022
TI  - Trends in hospital ownership of physician practices and the effect on processes
      to improve quality.
AB  - OBJECTIVES: Reports suggest a trend for physician practices to change ownership
      from physicians to hospitals. It remains unclear how this change affects quality
      of patient care. We report the effect of a change to hospital ownership on the
      use of care management processes (CMPs) and health information technology (IT)
      among practices in the United States. STUDY DESIGN: Trend analyses of 3 large
      national surveys of physician practices. METHODS: We included 2 cohorts of
      practices: large practices with 20 or more physicians and small/medium practices
      with fewer than 20 physicians. The main outcomes were the changes in CMP and
      health IT indices among practices that were acquired by hospitals. We used
      multivariate logistic regression to assess these changes. RESULTS: Large
      practices acquired by hospitals had larger increases in their CMP index than
      those that remained physician-owned (11.0-point increase vs 7.0-point decrease;
      adjusted P = .03). Small/medium practices acquired by hospitals had smaller but
      significantly higher increases in their CMP score (3.8 points vs 2.6 points;
      adjusted P = .04). Among all practices, there were no significant differences in
      the change of the health IT index. CONCLUSIONS: We found a significant increase
      in the use of CMPs among practices that were acquired by hospitals and no
      difference in health IT use. These findings suggest that a trend for hospitals to
      own physician practices may have a positive effect on chronic disease management
      and quality of care.

PMID- 27023023
TI  - Prevalence, effectiveness, and characteristics of pharmacy-based medication
      synchronization programs.
AB  - OBJECTIVES: The burden of visiting pharmacies to fill medications is a central
      contributor to nonadherence to maintenance medications. Recently, pharmacies have
      begun offering services that align prescription fill dates to allow patients to
      pick up all medications on a single visit. We evaluated the prevalence and
      structure of synchronization programs and evidence of their impact on adherence
      and clinical outcomes. STUDY DESIGN: Mixed-methods approach consisting of semi
      structured interviews, data from surveillance activities, and a systematic
      literature review. METHODS: We conducted interviews with opinion leaders from
      nonprofit advocacy organizations and exemplary synchronization programs. Program
      prevalence was determined using data from regular surveillance efforts. A
      literature review included Medline, EMBASE, Google Scholar, and general Internet
      searches. RESULTS: Synchronization programs exist in approximately 10% of
      independent, 6% of stand-alone chain, and 11% of retail store pharmacies. The
      majority of programs include a monthly pharmacist appointment and reminder
      communication. Programs reported the importance of pharmacist buy-in, technology
      to track and recruit patients, links to other healthcare services, and flexible
      solutions for managing costs and communication preferences. Although existing
      peer-reviewed literature suggests that synchronization improves adherence, more
      evidence is needed to evaluate its impact on patient-centered outcomes.
      CONCLUSIONS: As medication synchronization programs shift directions and compete
      for patients and payer resources, it will be more important than ever to
      rigorously evaluate their ability to improve clinical outcomes while also
      providing the growing number of patients managing multiple chronic conditions
      with the highest level of patient engagement and consumer choice.

PMID- 27023024
TI  - Impact of cost sharing on specialty drug utilization and outcomes: a review of
      the evidence and future directions.
AB  - OBJECTIVES: Specialty drugs often represent major medical advances for patients
      with few other effective options available, but high costs have attracted the
      attention of both payers and policy makers. We reviewed the evidence regarding
      the impact of cost sharing on utilization of specialty drugs indicated for
      rheumatoid arthritis (RA), multiple sclerosis (MS), and cancer, and on the use of
      nondrug medical services, health outcomes, and spending. STUDY DESIGN: Systematic
      review of Medline-indexed studies identified via an OVID search for articles
      published in English from 1995 to 2014, using combinations of terms for cost
      sharing and specialty drugs, and/or our 3 conditions of interest. We identified
      additional studies from reference lists. RESULTS: We identified 19 articles
      focusing on specialty drugs indicated for MS (n = 9), cancer (n = 8), and RA (n =
      8). Studies examined prescription abandonment (n = 3), initiation or any
      utilization (n = 8), adherence (n = 9), persistence/discontinuation (n = 7),
      number of claims (n = 1), and drug spending (n = 1). Findings varied by disease,
      but generally indicated stronger effects for noninitiation or abandonment of a
      prescription at the pharmacy and somewhat smaller effects for refill behavior and
      drug spending once patients initiated therapy. Studies have not examined
      specialty tier cost sharing seen under Medicare Part D or health insurance
      exchanges, nor effects on medical utilization, spending, or health outcomes.
      CONCLUSIONS: Evidence to date generally indicates reductions in specialty drug
      utilization associated with higher cost sharing; effects have varied by type of
      disease and specialty drug use outcome. We draw upon our findings and the gaps in
      evidence to summarize future directions for research and policy.

PMID- 27023025
TI  - Remembering the strength of weak ties.

PMID- 27023026
TI  - Introduction to the Special Issue on Experiments Involving the Outdoor Energetic
      Release of Radioactive Materials.

PMID- 27023027
TI  - International Outdoor Experiments and Models for Outdoor Radiological Dispersal
      Devices.

PMID- 27023028
TI  - Overview of the Full-scale Radiological Dispersal Device Field Trials.
AB  - In 2012, Defence Research and Development Canada, in partnership with a number of
      other Canadian and International organizations, led a series of three field
      trials designed to simulate a Radiological Dispersal Device (RDD). These trials,
      known as the Full-Scale RDD (FSRDD) Field Trials, involved the explosive
      dispersal of a short-lived radioactive tracer ((140)La, t1/2 = 40.293 h). The
      FSRDD Field Trials required a significant effort in their planning, preparation,
      and execution to ensure that they were carried out in a safe, efficient manner
      and that the scientific goals of the trials were met. The discussion presented
      here details the planning and execution of the trials, outlines the relevant
      radiation safety aspects, provides a summary of the source term and atmospheric
      conditions for the three dispersal events, and provides an overview of the
      measurements that were made to track the plumes and deposition patterns.

PMID- 27023029
TI  - Measuring Concentrations of Particulate 140La in the Air.
AB  - Air sampling systems were deployed to measure the concentration of radioactive
      material in the air during the Full-Scale Radiological Dispersal Device Field
      Trials. The air samplers were positioned 100-600 m downwind of the release point.
      The filters were collected immediately and analyzed in a field laboratory.
      Quantities for total activity collected on the air filters are reported along
      with additional information to compute the average or integrated air
      concentrations. 

PMID- 27023030
TI  - Real Time in Situ Gamma Radiation Measurements of the Plume Evolution from the
      Full-Scale Radiological Dispersal Device Field Trials.
AB  - During the Full-Scale Radiological Dispersal Device Field Trials carried out in
      Suffield in 2012, several suites of detection and sampling equipment were used to
      measure and characterize the explosive dispersal of the short half-life
      radioactive tracer Lanthanum-140 ((140)La). The equipment deployed included
      networks of in situ real-time radiation monitoring detectors providing
      measurements of different sensitivities and characteristics. A dense array of
      lower sensitivity detectors was established near field, ranging from 10 to 450 m
      from the detonation location. A sparser array of more sensitive detectors was
      established in the far field (150 m to 3.5 km from the detonation location). Each
      was used to collect and report the dose rate data from the radioactive plume
      passage with a sample time resolution of 1 s. The two systems went through
      independent calibrations and were compared and shown to be consistent with each
      other. The in situ gamma radiation measurements have allowed the movement and
      evolution of the plume to be described and to identify deposition rates and non
      uniformities in the temporal shape of the plume. This knowledge could be applied
      for emergency planning guidance for the case of release of radioactive material
      by a radiological dispersive device.

PMID- 27023031
TI  - Scanning Lidar Measurements of the Full-Scale RDD Field Trial Puff Plumes.
AB  - A vertically scanning lidar (light/radar) was used to measure the time evolution
      of clouds generated by a small explosive device. Vertical sweeps were performed
      at a downwind distance of 105 m from the detonation. The measured quantity
      obtained from the lidar was the light extinction coefficient. This quantity is
      directly proportional to the aerosol concentration. The background aerosol value
      was set to 0.0001 m (-1) (assuming a visibility of 40 km), and assuming the
      scattering properties of the explosively generated cloud is the same as the
      background aerosol, the authors found that the instantaneous maximal local
      concentration of aerosol in the cloud did not exceed 500 times the background
      aerosol value, and the instantaneous concentration was typically less than five
      times the background aerosol value. In the two trials that were done, the volumes
      of the clouds were reasonably close at 2,700 m(3) and 4,000 m(3), respectively.

PMID- 27023032
TI  - Deposition Measurements From the Full-Scale Radiological Dispersal Device Field
      Trials.
AB  - In 2012, Defence Research and Development Canada led a series of experiments,
      titled the Full-Scale Radiological Dispersal Device Field Trials, in which short
      lived radioactive material was explosively dispersed and the resulting plume and
      deposition were characterized through a variety of methods. Presented here are
      the results of a number of measurements that were taken to characterize the
      radioactive ground deposition. These included in situ gamma measurements,
      deposition filter samples, and witness plate measurements that were taken in situ
      with handheld beta survey meters. The results from the different measurement
      techniques are compared to each other and to a simple deposition model. Results
      showed that approximately 3% of the original source activity was deposited in the
      immediate vicinity of ground zero, and an additional 15-30% of the original
      activity was deposited within 450 m of ground zero. Implications of these results
      for emergency response are discussed. 

PMID- 27023033
TI  - Aerial Mobile Radiation Survey Following Detonation of a Radiological Dispersal
      Device.
AB  - A series of experiments was conducted in 2012 at the Defence Research and
      Development Canada's Suffield Research Centre in Alberta, Canada, during which
      three radiological dispersal devices were detonated. The detonations released
      radioactive (140)La into the air, which was then carried by winds and detectable
      over distances of up to 2 km. The Nuclear Emergency Response group of Natural
      Resources Canada conducted airborne radiometric surveys shortly following the
      explosions to map the pattern of radioactivity deposited on the ground. The
      survey instrument suite was based on large volume NaI(Tl) scintillation gamma
      radiation detectors, which were situated in a basket mounted exterior to the
      helicopter and oriented end-to-end to maximize the sensitivity. A standard
      geophysical data treatment was used to subtract backgrounds and to correct the
      data to produce counts due to (140)La at the nominal altitude. Sensitivity
      conversion factors obtained from Monte Carlo simulations were then applied to
      express the measurements in terms of surface activity concentration in kBq m(-2).
      Integrated over the survey area, the results indicate that only 20 to 25% of the
      bomb's original inventory of radioactive material is deposited within a 1.5-km
      radius of ground zero. These results can be accommodated with a simple model for
      the RDD behavior and atmospheric dispersion.

PMID- 27023034
TI  - Particle Density Using Deposition Filters at the Full Scale RDD Experiments.
AB  - During the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials carried
      out in Suffield, Alberta, Canada, several suites of detection equipment and
      software models were used to measure and characterize the ground deposition. The
      FSRDD Field Trials were designed to disperse radioactive lanthanum of known
      activity to better understand such an event. This paper focuses on one means of
      measuring both concentration and the particle size distribution of the deposition
      using electrostatic filters placed around the trial site to collect deposited
      particles for analysis. The measurements made from ground deposition filters
      provided a basis to guide modeling and validate results by giving insight on how
      particles are distributed by a plume. 

PMID- 27023035
TI  - Validation of the DIFFAL, HPAC and HotSpot Dispersion Models Using the Full-Scale
      Radiological Dispersal Device (FSRDD) Field Trials Witness Plate Deposition
      Dataset.
AB  - Three atmospheric dispersion models--DIFFAL, HPAC, and HotSpot--of differing
      complexities have been validated against the witness plate deposition dataset
      taken during the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials.
      The small-scale nature of these trials in comparison to many other historical
      radiological dispersion trials provides a unique opportunity to evaluate the near
      field performance of the models considered. This paper performs validation of
      these models using two graphical methods of comparison: deposition contour plots
      and hotline profile graphs. All of the models tested are assessed to perform
      well, especially considering that previous model developments and validations
      have been focused on larger-scale scenarios. Of the models, HPAC generally
      produced the most accurate results, especially at locations within ~100 m of GZ.
      Features present within the observed data, such as hot spots, were not well
      modeled by any of the codes considered. Additionally, it was found that an
      increase in the complexity of the meteorological data input to the models did not
      necessarily lead to an improvement in model accuracy; this is potentially due to
      the small-scale nature of the trials.

PMID- 27023036
TI  - National Atmospheric Release Advisory Center Dispersion Modeling of the Full
      scale Radiological Dispersal Device (FSRDD) Field Trials.
AB  - The results of the National Atmospheric Release Advisory Center (NARAC) model
      simulations are compared to measured data from the Full-Scale Radiological
      Dispersal Device (FSRDD) field trials. The series of explosive radiological
      dispersal device (RDD) experiments was conducted in 2012 by Defence Research and
      Development Canada (DRDC) and collaborating organizations. During the trials, a
      wealth of data was collected, including a variety of deposition and air
      concentration measurements. The experiments were conducted with one of the stated
      goals being to provide measurements to atmospheric dispersion modelers. These
      measurements can be used to facilitate important model validation studies. For
      this study, meteorological observations recorded during the tests are input to
      the diagnostic meteorological model, ADAPT, which provides 3-D, time-varying mean
      wind and turbulence fields to the LODI dispersion model. LODI concentration and
      deposition results are compared to the measured data, and the sensitivity of the
      model results to changes in input conditions (such as the particle activity size
      distribution of the source) and model physics (such as the rise of the buoyant
      cloud of explosive products) is explored. The NARAC simulations predicted the
      experimentally measured deposition results reasonably well considering the
      complexity of the release. Changes to the activity size distribution of the
      modeled particles can improve the agreement of the model results to measurement. 

PMID- 27023037
TI  - The Sensitivity of Atmospheric Dispersion Calculations in Near-field
      Applications: Modeling of the Full Scale RDD Experiments with Operational Models
      in Canada, Part I.
AB  - Three radiological dispersal devices were detonated in 2012 under controlled
      conditions at Defence Research and Development Canada's Experimental Proving
      Grounds in Suffield, Alberta. Each device comprised a 35-GBq source of (140)La.
      The dataset obtained is used in this study to assess the MLCD, ADDAM, and RIMPUFF
      atmospheric dispersion models. As part one of a two-part study, this paper
      focuses on examining the capabilities of the above three models and evaluating
      how well their predictions of air concentration and ground deposition match
      observations from the full-scale RDD experiments.

PMID- 27023038
TI  - Radiation Modeling and Finite Cloud Effects for Atmospheric Dispersion
      Calculations in Near-field Applications: Modeling of the Full Scale RDD
      Experiments with Operational Models in Canada, Part II.
AB  - Three radiological dispersal devices were detonated in 2012 under controlled
      conditions at Defence Research and Development Canada's Experimental Proving
      Grounds in Suffield, Alberta. Each device comprised a 35-GBq source of (140)La.
      The dataset obtained is used in this study to assess the MLCD, ADDAM, and RIMPUFF
      atmospheric dispersion models. As a continuation of Lebel et al. (2016), this
      paper examines different methodologies for making dose estimates with atmospheric
      dispersion models.

PMID- 27023039
TI  - Using Atmospheric Dispersion Theory to Inform the Design of a Short-lived
      Radioactive Particle Release Experiment.
AB  - Atmospheric dispersion theory can be used to predict ground deposition of
      particulates downwind of a radionuclide release. This paper uses standard
      formulations found in Gaussian plume models to inform the design of an
      experimental release of short-lived radioactive particles into the atmosphere.
      Specifically, a source depletion algorithm is used to determine the optimum
      particle size and release height that maximizes the near-field deposition while
      minimizing both the required source activity and the fraction of activity lost to
      long-distance transport. The purpose of the release is to provide a realistic
      deposition pattern that might be observed downwind of a small-scale vent from an
      underground nuclear explosion. The deposition field will be used, in part, to
      study several techniques of gamma radiation survey and spectrometry that could be
      used by an On-Site Inspection team investigating such an event. 

PMID- 27023040
TI  - PRex: An Experiment to Investigate Detection of Near-field Particulate Deposition
      from a Simulated Underground Nuclear Weapons Test Vent.
AB  - A radioactive particulate release experiment to produce a near-field ground
      deposition representative of small-scale venting from an underground nuclear test
      was conducted to gather data in support of treaty capability development
      activities. For this experiment, a CO2-driven "air cannon" was used to inject
      (140)La, a radioisotope of lanthanum with 1.7-d half-life and strong gamma-ray
      emissions, into the lowest levels of the atmosphere at ambient temperatures.
      Witness plates and air samplers were laid out in an irregular grid covering the
      area where the plume was anticipated to deposit based on climatological wind
      records. This experiment was performed at the Nevada National Security Site,
      where existing infrastructure, radiological procedures, and support personnel
      facilitated planning and execution of the work. A vehicle-mounted NaI(Tl)
      spectrometer and a polyvinyl toluene-based backpack instrument were used to
      survey the deposited plume. Hand-held instruments, including NaI(Tl) and
      lanthanum bromide scintillators and high purity germanium spectrometers, were
      used to take in situ measurements. Additionally, three soil sampling techniques
      were investigated and compared. The relative sensitivity and utility of sampling
      and survey methods are discussed in the context of on-site inspection.

PMID- 27023044
TI  - The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for
      Cervical Cancer Screening: A Modeling Analysis.
AB  - BACKGROUND: Consensus United States cervical cancer screening guidelines
      recommend use of combination Pap plus human papillomavirus (HPV) testing for
      women aged 30 to 65 years. An HPV test was approved by the Food and Drug
      Administration in 2014 for primary cervical cancer screening in women age 25
      years and older. Here, we present the results of clinical-economic comparisons of
      Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus
      DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV
      primary) for cervical cancer screening. METHODS: A health state transition
      (Markov) model with 1-year cycling was developed using epidemiologic, clinical,
      and economic data from healthcare databases and published literature. A
      hypothetical cohort of one million women receiving triennial cervical cancer
      screening was simulated from ages 30 to 70 years. Screening strategies compared
      HPV primary to co-testing. Outcomes included total and incremental differences in
      costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies,
      and quality-adjusted life years for cost-effectiveness calculations.
      Comprehensive sensitivity analyses were performed. RESULTS: In a simulation
      cohort of one million 30-year-old women modeled up to age 70 years, the model
      predicted that screening with HPV primary testing instead of co-testing could
      lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the
      simulation, co-testing demonstrated a greater number of lifetime quality-adjusted
      life years (22,334) and yielded $39.0 million in savings compared with HPV
      primary, thereby conferring greater effectiveness at lower cost. CONCLUSIONS:
      Model results demonstrate that co-testing has the potential to provide improved
      clinical and economic outcomes when compared with HPV primary. While actual cost
      and outcome data are evaluated, these findings are relevant to U.S. healthcare
      payers and women's health policy advocates seeking cost-effective cervical cancer
      screening technologies.

PMID- 27023045
TI  - Gait variability in people with neurological disorders: A systematic review and
      meta-analysis.
AB  - There has been growing evidence showing gait variability provides unique
      information about gait characteristics in neurological disorders. This study
      systemically reviewed and quantitatively synthesized (via meta-analysis) existing
      evidence on gait variability in various neurological diseases, including
      Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), cerebellar ataxia
      (CA), Huntington's disease (HD), multiple sclerosis (MS), and Parkinson's disease
      (PD). Keyword search were conducted in PubMed, Web of science, Cumulative Index
      to Nursing and Allied Health Literature, and Cochrane Library. Meta-analysis was
      performed to estimate the pooled effect size for gait variability for each
      neurological group. Meta-regression was performed to compare gait variability
      across multiple groups with neurological diseases. Gait variability of 777
      patients with AD, ALS, CA, HD, MS, or PD participating in 25 studies was included
      in meta-analysis. All pathological groups had increased amount of gait
      variability and loss of fractal structure of gait dynamics compared to healthy
      controls, and gait variability differentiated distinctive neurological
      conditions. The HD groups had the highest alterations in gait variability among
      all pathological groups, whereas the PD, AD and MS groups had the lowest.
      Interventions that aim to improve gait function in patients with neurological
      disorders should consider the heterogeneous relationship between gait variability
      and neurological conditions. 

PMID- 27023046
TI  - Animal inference on human mitochondrial diseases.
AB  - Several pathological mutations in the human mitochondrial genome have been
      characterized based on medical, genetic and biochemical evidence. The observation
      that the structure and core functions of the mitochondrial genome are conserved
      from animals to man suggests that the analysis of animal variation may be
      informative to further characterize, and possibly predict, human pathological
      variants. We studied the distribution of sequence site-wise diversity and
      structural heterogeneity (based on several scales of hydrophobicity and
      supercomplex classification of mitochondrial genes) at different taxonomic levels
      in ~15,000 human and animal genomes. We found that human pathological mutations
      tend to lay in regions of low diversity and that states that are pathological in
      humans appear to be extremely rare in animals, with two noticeable exceptions
      (T10663C and C14568T). Focusing on hydrophobicity, as possibly the most general
      site-wise functional parameter of a protein, we deploy the observed range of
      hydrophobicity in mammals as a proxy for the range of permissible states
      compatible with an efficient functioning of the mitochondrial machinery. We show
      that, while non pathological human variants tend to fall within the hypothesized
      range, pathological mutations generally fall outside this range. We further
      analyzed this distribution quantitatively to show that the estimated probability
      of observed states can indeed be used to predict the pathogenicity of a mutation
      in humans. This study provides a proof of principle that animal data can indeed
      be informative to predict the pathogenicity of a human mutation alongside, or in
      the absence of, additional evidence.

PMID- 27023047
TI  - Gutzwiller wave function for finite systems: superconductivity in the Hubbard
      model.
AB  - We study the superconducting phase of the Hubbard model using the Gutzwiller
      variational wave function (GWF) and the recently proposed diagrammatic expansion
      technique (DE-GWF). The DE-GWF method works on the level of the full GWF and in
      the thermodynamic limit. Here, we consider a finite-size system to study the
      accuracy of the results as a function of the system size (which is practically
      unrestricted). We show that the finite-size scaling used, e.g. in the variational
      Monte Carlo method can lead to significant, uncontrolled errors. The presented
      research is the first step towards applying the DE-GWF method in studies of
      inhomogeneous situations, including systems with impurities, defects,
      inhomogeneous phases, or disorder. 

PMID- 27023048
TI  - Signal transducer and activator of transcription 3 signaling as a potential
      target to treat muscle wasting diseases.
AB  - PURPOSE OF REVIEW: The review summarizes our current knowledge of the role of
      signal transducer and activator of transcription 3 (STAT3) signaling in skeletal
      muscle regeneration and the maintenance of muscle mass. RECENT FINDINGS: STAT3
      signaling plays a pivotal role in regulating the function of multiple cell types
      in skeletal muscle. This includes muscle stem cells, myofibers, and macrophages.
      It regulates muscle stem cell function by antagonizing self-renewal. STAT3 also
      functions in myofibers to regulate skeletal muscle mass. This is highly relevant
      under pathological conditions where STAT3 activation promotes protein degradation
      and muscle atrophy. Transient pharmacological inhibition of STAT3 partially
      prevents muscle wasting. However, the mechanisms responsible for the improvement
      of muscle condition are not currently well understood. This is because of the
      complexity of the system, as STAT3 has a critical role in regulating the function
      of several cell types residing in skeletal muscle. SUMMARY: Muscle wasting is
      associated with several human diseases such as muscle dystrophies or cancer
      cachexia. However, currently there are no effective treatments for this
      condition, and there is a critical need to identify new potential targets for the
      development of efficient therapeutic approaches.

PMID- 27023049
TI  - Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic
      target in melanoma.
AB  - Despite the recent success of MAPK and immune checkpoint inhibitors in advanced
      melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of
      these therapeutic approaches. Therapy resistance in melanoma is not solely driven
      by genetic evolution, but also by epigenetically driven adaptive plasticity.
      Melanoma cells are shifting between different transcriptional programs, cell
      cycle states and differentiation phenotypes reflecting a highly dynamic potential
      to adapt to various exogenous stressors including immune attack or cancer
      therapies. This review will focus on the dynamic interconversion and overlap
      between different melanoma cell phenotypes in the context of therapy resistance
      and a dynamically changing multicellular microenvironment.

PMID- 27023050
TI  - Polyurethane versus silicone catheters for central venous port devices implanted
      at the forearm.
AB  - PURPOSE: We aimed to analyse short and long-term complications of polyurethane
      (PU) versus silicone catheters used in totally implantable venous-access ports
      (TIVAPs) implanted at the forearm. METHODS: Retrospective analysis of 698
      consecutively implanted TIVAPs was performed. Primary end-points were defined as
      rates of major complications associated with either type of central venous port
      catheter. Technical success rate, device service interval as well as minor
      complications not requiring port explantation were defined as secondary end
      points. RESULTS: A total of 698 port devices were implanted in 681 patients, 396
      equipped with a PU catheter, 302 with a silicone catheter. The technical success
      rate was 99.9% with no major periprocedural complications. During follow-up a
      total of 211 complications in 146 patients were observed (1.0/1000 catheter
      days), 183 occurred associated with PU catheters (1.8/100 catheter days), 28
      (0.3/1000 catheter days) with silicone catheters (log rank test p < 0.0001).
      Catheter-related bloodstream infections as well as thrombotic complications
      occurred significantly more frequently with PU catheters, while silicone
      catheters exhibited a trend towards a higher rate of mechanical failure such as
      disconnection or catheter rupture. Major complications requiring explantation of
      the device occurred more frequently with PU-based catheters (10.6%) compared to
      silicone catheter carrying ports (4.6%, log rank test p < 0.001). CONCLUSION: PU
      catheters are more susceptible to catheter-related infections and exhibit a
      higher thrombogenicity, compared to silicone catheters. Silicone catheters
      instead exhibit a trend towards decreased mechanical stability.

PMID- 27023052
TI  - Controlling Random Lasing with Three-Dimensional Plasmonic Nanorod Metamaterials.
AB  - Plasmonics has brought revolutionary advances to laser science by enabling deeply
      subwavelength nanolasers through surface plasmon amplification. However, the
      impact of plasmonics on other promising laser systems has so far remained
      elusive. Here, we present a class of random lasers enabled by three-dimensional
      plasmonic nanorod metamaterials. While dense metallic nanostructures are usually
      detrimental to laser performance due to absorption losses, here the lasing
      threshold keeps decreasing as the volume fraction of metal is increased up to
      ~0.07. This is ~460 times higher than the optimal volume fraction reported thus
      far. The laser supports spatially confined lasing modes and allows for efficient
      modulation of spectral profiles by simply tuning the polarization of the pump
      light. Full-field speckle-free imaging at micron-scales has been achieved by
      using plasmonic random lasers as the illumination sources. Our findings show that
      plasmonic metamaterials hold potential to enable intriguing coherent optical
      sources. 

PMID- 27023051
TI  - A high-throughput multiplex genetic detection system for Helicobacter pylori
      identification, virulence and resistance analysis.
AB  - AIM: We established a high-throughput multiplex genetic detection system (HMGS)
      for identification of Helicobacter pylori with concomitant analysis of virulence
      and drug resistance. MATERIALS & METHODS: Confirmed 132 H. pylori cultures from
      gastric biopsies were screened by 20-gene site-HMGS, sequencing and E-test.
      RESULTS: HMGS was highly sensitive and specific for H. pylori identification.
      Concordance rate between HMGS and sequencing averaged 94.5% (virulence genes) and
      97.3% (resistance genes). Observed resistance rates to four mainstream
      antibiotics were high, except for amoxicillin. Significant association between
      virulence genotype and risks for specific gastrointestinal diseases was found for
      five genes. Metronidazole resistance in peptic ulcer patients was significantly
      higher. CONCLUSION: HMGS is an effective method for H. pylori identification and
      analysis of virulence and drug resistance.

PMID- 27023053
TI  - Optical Coherence Tomography Angiography in Dystrophies.
AB  - Optical coherence tomography (OCT) angiography (OCT-A) represents an innovative
      imaging technique which can delineate the retinal and choroidal vascular
      networks. OCT-A in the assessment of chorio-retinal dystrophies reveal
      alterations especially located at the level of the deep capillary plexus and the
      choriocapillaris. This information can have a direct implication on the
      understanding of the pathogenesis of dystrophies and for their future therapeutic
      management. 

PMID- 27023054
TI  - Microfluidic Flow Chambers Using Reconstituted Blood to Model Hemostasis and
      Platelet Transfusion In Vitro.
AB  - Blood platelets prepared for transfusion gradually lose hemostatic function
      during storage. Platelet function can be investigated using a variety of
      (indirect) in vitro experiments, but none of these is as comprehensive as
      microfluidic flow chambers. In this protocol, the reconstitution of
      thrombocytopenic fresh blood with stored blood bank platelets is used to simulate
      platelet transfusion. Next, the reconstituted sample is perfused in microfluidic
      flow chambers which mimic hemostasis on exposed subendothelial matrix proteins.
      Effects of blood donation, transport, component separation, storage and pathogen
      inactivation can be measured in paired experimental designs. This allows reliable
      comparison of the impact every manipulation in blood component preparation has on
      hemostasis. Our results demonstrate the impact of temperature cycling, shear
      rates, platelet concentration and storage duration on platelet function. In
      conclusion, this protocol analyzes the function of blood bank platelets and this
      ultimately aids in optimization of the processing chain including phlebotomy,
      transport, component preparation, storage and transfusion. 

PMID- 27023055
TI  - Corrigendum: MAZ mediates the cross-talk between CT-1 and NOTCH1 signaling during
      gliogenesis.

PMID- 27023057
TI  - Cardiology in Primary Care Handler Clive Cardiology in Primary Care 325pp
      Radcliffe Publishing 9781857758337 1857758331.
AB  - In recent years, the burden of health care has been shifting towards primary
      care. It is now responsible for the prevention, treatment and follow-up of many
      diseases, whereas in the past its main role was to act as a referral service.

PMID- 27023058
TI  - NATN Standards and Recommendations for Safe Perioperative Practice Beesley John
      Pirie Susan NATN Standards and Recommendations for Safe Perioperative Practice
      249pp National Association of Theatre Nurses 9781904290032 1904290035.
AB  - This publication identifies standards and recommendations for practice in key
      areas of perioperative care. Sections include legal and ethical issues, risk
      management, infection control, decontamination, principles of anaesthetics and
      clinical effectiveness. A wide range of topics is discussed in some depth. Each
      topic contains a standard statement, supporting discussion and recommendations
      for inclusion in local policies.

PMID- 27023056
TI  - Theoretical Study on the Dynamic Behavior of a Plate-Like Micro-Cantilever with
      Multiple Particles Attached.
AB  - In this study, the dynamic characteristics of a plate-like micro-cantilever beam
      attached with multiple concentrated masses are studied. The vibration modes of
      the cantilever plate are represented by combinations of beam functions. Using
      classical mechanics (the effect of size is not considered) and the corrected
      Cosserat's theorem (the effect of size is considered), we employ the Lagrange
      equations to establish a dynamic model of the plate-like micro-cantilever beam
      attached with multiple concentrated masses. The accuracy of the model proposed in
      this paper is verified by comparing with the results of published literature.
      Then, the natural frequencies of the cantilever plates are calculated with self
      compiled algorithms, and the results of the plates with 1-5 masses are displayed.
      The results are in high accordance with the exact solution, and all errors are
      within 0.5%. The analysis shows that the proposed model and analysis method
      converges quickly and is highly efficient. In addition, the effects of
      characteristic lengths, Poisson's ratios and plate thickness on the micro
      cantilever plate's resonant frequency for the first five modes are analyzed. 

PMID- 27023059
TI  - Induced Pluripotent Stem Cell-conditioned Medium Suppressed Melanoma
      Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity.
AB  - Induced pluripotent stem cells (iPSCs) can secrete cytokines that are involved in
      T-cell development and affect cytotoxic activity. To assess the effect of iPSC
      conditioned medium on tumorigenicity, we retrieved splenocytes from B6 mice and
      cocultured them with or without irradiated B16 melanoma cells, mouse interleukin
      2 (mIL-2), or iPSC-conditioned medium. Splenocyte cytotoxicity assays against B16
      melanoma cells [as cytotoxic T lymphocyte (CTL) activity] and P815 cells [as
      natural killer (NK) activity] were performed. IL-10 and interferon-gamma
      concentrations were measured. An in vivo subcutaneous B16 melanoma growth model
      was performed in B6 mice and treated with iPSC-conditioned medium. The lymphocyte
      subpopulation depletion test was performed to determine effectors against B16
      melanoma cells. We found that unstimulated splenocytes had little cytotoxic
      activity. Without tumor cells, mIL-2 could augment iPSC-conditioned medium
      treated CTL and NK activities (P<0.01). With irradiated tumor cells, mIL-2
      treatment of splenocytes could not enhance CTL or NK activity, but iPSC
      conditioned medium could enhance CTL and NK activity (P<0.001). Irradiated tumor
      cells induced mice splenocytes to secrete more IL-10, similar to mIL-2 treatment,
      but not iPSC-conditioned medium treatment. mIL-2 had better efficacy than
      conditioned medium in inducing splenocyte interferon-gamma production. The CTL
      and NK cell depletion test showed that the immunostimulating effect of iPSC
      conditioned medium on splenocytes was through the enhancement of NK cellular
      activity (P<0.05). The subcutaneous melanoma growth model showed that B16-bearing
      mice treated with an iPSC-conditioned medium intraperitoneal injection had a
      decreased tumor growth rate (P<0.01). Our study suggests that iPSC-conditioned
      medium had a protective effect against tumor-induced immunosuppression through
      the enhancement of host NK cellular activity. 

PMID- 27023060
TI  - Successful Anti-PD-1 Antibody Treatment in a Metastatic Melanoma Patient With
      Known Severe Autoimmune Disease.
AB  - Pembrolizumab, an anti-programmed death-1 monoclonal antibody, has been approved
      by the Food and Drug Administration in 2014 on the basis of improved progression
      free and overall survival in metastatic melanoma. We report for the first time a
      successful treatment with a programmed death-1 antibody in a 69-year-old
      metastastic melanoma patient with a Churg-Strauss lung vasculitis and a prior
      ipilimumab-induced autoimmune colitis. This case report suggests that
      pembrolizumab can be given with caution to patients with underlying autoimmune
      disease. As the use of checkpoint inhibitors expands, knowledge about their
      safety in patients with underlying autoimmune diseases will become increasingly
      important, in particular because these patients are typically excluded from
      clinical trials with immune-checkpoint inhibitors. 

PMID- 27023061
TI  - Genomic Footprints in Selected and Unselected Beef Cattle Breeds in Korea.
AB  - Korean Hanwoo cattle have been subjected to intensive artificial selection over
      the past four decades to improve meat production traits. Another three cattle
      varieties very closely related to Hanwoo reside in Korea (Jeju Black and Brindle)
      and in China (Yanbian). These breeds have not been part of a breeding scheme to
      improve production traits. Here, we compare the selected Hanwoo against these
      similar but presumed to be unselected populations to identify genomic regions
      that have been under recent selection pressure due to the breeding program. Rsb
      statistics were used to contrast the genomes of Hanwoo versus a pooled sample of
      the three unselected population (UN). We identified 37 significant SNPs (FDR
      corrected) in the HW/UN comparison and 21 known protein coding genes were within
      1 MB to the identified SNPs. These genes were previously reported to affect
      traits important for meat production (14 genes), reproduction including mammary
      gland development (3 genes), coat color (2 genes), and genes affecting behavioral
      traits in a broader sense (2 genes). We subsequently sequenced (Illumina HiSeq
      2000 platform) 10 individuals of the brown Hanwoo and the Chinese Yanbian to
      identify SNPs within the candidate genomic regions. Based on allele frequency
      differences, haplotype structures, and literature research, we singled out one
      non-synonymous SNP in the APP gene (APP: c.569C>T, Ala199Val) and predicted the
      mutational effect on the protein structure. We found that protein-protein
      interactions might be impaired due to increased exposed hydrophobic surfaces of
      the mutated protein. The APP gene has also been reported to affect meat
      tenderness in pigs and obesity in humans. Meat tenderness has been linked to
      intramuscular fat content, which is one of the main breeding goals for brown
      Hanwoo, potentially supporting a causal influence of the herein described nsSNP
      in the APP gene. 

PMID- 27023062
TI  - Lactic Acid Fermentation of Cactus Cladodes (Opuntia ficus-indica L.) Generates
      Flavonoid Derivatives with Antioxidant and Anti-Inflammatory Properties.
AB  - Cactus pear (Opuntia ficus-indica L.) is widely distributed in the arid and semi
      arid regions throughout the world. In the last decades, the interest towards
      vegetative crop increased, and cladodes are exploited for nutraceutical and
      health-promoting properties. This study aimed at investigating the capacity of
      selected lactic acid bacteria to increase the antioxidant and anti-inflammatory
      properties of cactus cladodes pulp, with the perspective of producing a
      functional ingredient, dietary supplement or pharmaceutical preparation.
      Preliminarily, the antioxidant activity was determined through in vitro assays.
      Further, it was confirmed through ex vivo analysis on intestinal Caco-2/TC7
      cells, and the profile of flavonoids was characterized. Cactus cladode pulp was
      fermented with lactic acid bacteria, which were previously selected from plant
      materials. Chemically acidified suspension, without bacterial inoculum and
      incubated under the same conditions, was used as the control. Lactobacillus
      plantarum CIL6, POM1 and 1MR20, Lactobacillus brevis POM2 and POM4, Lactobacillus
      rossiae 2LC8 and Pediococcus pentosaceus CILSWE5 were the best growing strains.
      Fermentation of cladode pulp with L. brevis POM2 and POM4 allowed the highest
      concentration of gamma-amino butyric acid. Lactic acid fermentation had
      preservative effects (P<0.05) on the levels of vitamin C and carotenoids. Two
      flavonoid derivatives (kaemferol and isorhamnetin) were identified in the ethyl
      acetate extracts, which were considered to be the major compounds responsible for
      the increased radical scavenging activity. After inducing oxidative stress by IL
      1beta, the increased antioxidant activity (P<0.05) of fermented cladode pulp was
      confirmed using Caco-2/TC7 cells. Fermented cladode pulp had also immune
      modulatory effects towards Caco-2 cells. Compared to the control, fermented
      cladode pulp exhibited a significantly (P<0.05) higher inhibition of IL-8,
      TNFalpha and prostaglandins PGE2 synthesis. The highest functional effect was
      found using ethyl acetate extracts. In conclusion, fermentation, especially with
      L. plantarum strains and L. brevis POM4, enhanced the antioxidant and immune
      modulation features of cladode pulp. 

PMID- 27023063
TI  - Reversible Morphological Control of Tubulin-Encapsulating Giant Liposomes by
      Hydrostatic Pressure.
AB  - Liposomes encapsulating cytoskeletons have drawn much recent attention to develop
      an artificial cell-like chemical-machinery; however, as far as we know, there has
      been no report showing isothermally reversible morphological changes of liposomes
      containing cytoskeletons because the sets of various regulatory factors, that is,
      their interacting proteins, are required to control the state of every reaction
      system of cytoskeletons. Here we focused on hydrostatic pressure to control the
      polymerization state of microtubules (MTs) within cell-sized giant liposomes
      (diameters ~10 MUm). MT is the cytoskeleton formed by the polymerization of
      tubulin, and cytoskeletal systems consisting of MTs are very dynamic and play
      many important roles in living cells, such as the morphogenesis of nerve cells
      and formation of the spindle apparatus during mitosis. Using real-time imaging
      with a high-pressure microscope, we examined the effects of hydrostatic pressure
      on the morphology of tubulin-encapsulating giant liposomes. At ambient pressure
      (0.1 MPa), many liposomes formed protrusions due to tubulin polymerization within
      them. When high pressure (60 MPa) was applied, the protrusions shrank within
      several tens of seconds. This process was repeatedly inducible (around three
      times), and after the pressure was released, the protrusions regenerated within
      several minutes. These deformation rates of the liposomes are close to the
      velocities of migrating or shape-changing living cells rather than the shortening
      and elongation rates of the single MTs, which have been previously measured.
      These results demonstrate that the elongation and shortening of protrusions of
      giant liposomes is repeatedly controllable by regulating the polymerization state
      of MTs within them by applying and releasing hydrostatic pressure.

PMID- 27023065
TI  - The temporoparietal fascia flap folded into a ball in the treatment of
      retroauricular cerebrospinal fluid fistulae after posterior fossa surgery.
AB  - BACKGROUND: Skull base and posterior fossa surgeries are sometimes complicated by
      cerebrospinal fluid (CSF) fistulae, which may be challenging to treat. They can
      lead to meningitis, increasing global morbidity and mortality. In case of failed
      medical treatment, revision surgery may be required. "Fat packing" (adipose
      tissue grafts) is usually used to close the communication between the
      intracranial contents and the cutaneous tissue, and to fill the dead space
      created by the skull base surgery. Vascularised flaps can also be used. They seem
      more efficient, especially in multi-operated patients or after radiotherapy, when
      cutaneous tissue is adhesive and fragile. METHODS: Temporoparietal fascia (TPF)
      flap is a regional flap; it has reliable blood supply and can cover temporal and
      retroauricular defects. Folded into a ball, it can fill small dead spaces and can
      be skin grafted in case of cutaneous defect. RESULTS AND CONCLUSIONS: We present
      a simple surgical solution to manage recurrent retroauricular CSF fistulae after
      posterior fossa surgery using a pedicled TPF flap folded into a ball.

PMID- 27023064
TI  - Role of Nrf2, HO-1 and GSH in Neuroblastoma Cell Resistance to Bortezomib.
AB  - The activation of Nrf2 has been demonstrated to play a crucial role in cancer
      cell resistance to different anticancer therapies. The inhibition of proteasome
      activity has been proposed as a chemosensitizing therapy but the activation of
      Nrf2 could reduce its efficacy. Using the highly chemoresistant neuroblastoma
      cells HTLA-230, here we show that the strong reduction in proteasome activity,
      obtained by using low concentration of bortezomib (BTZ, 2.5 nM), fails in
      reducing cell viability. BTZ treatment favours the binding of Nrf2 to the ARE
      sequences in the promoter regions of target genes such as heme oxygenase 1 (HO
      1), the modulatory subunit of gamma-glutamylcysteine ligase (GCLM) and the
      transporter for cysteine (x-CT), enabling their transcription. GSH level is also
      increased after BTZ treatment. The up-regulation of Nrf2 target genes is
      responsible for cell resistance since HO-1 silencing and GSH depletion
      synergistically decrease BTZ-treated cell viability. Moreover, cell exposure to
      all-trans-Retinoic acid (ATRA, 3 MUM) reduces the binding of Nrf2 to the ARE
      sequences, decreases HO-1 induction and lowers GSH level increasing the efficacy
      of bortezomib. These data suggest the role of Nrf2, HO-1 and GSH as molecular
      targets to improve the efficacy of low doses of bortezomib in the treatment of
      malignant neuroblastoma. 

PMID- 27023066
TI  - Clinical presentation and in-hospital death in acute pulmonary embolism: does
      cancer matter?
AB  - Cancer is one of the most common risk factors for acute pulmonary embolism (PE),
      but only few studies report on the short-term outcome of patients with PE and a
      history of cancer. The aim of the study was to assess whether a cancer diagnosis
      affects the clinical presentation and short-term outcome in patients hospitalized
      for PE who were included in the Italian Pulmonary Embolism Registry. All-cause
      and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451
      (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation
      in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer
      patients). Patients with and without cancer were similar concerning clinical
      status at presentation. Patients with cancer less commonly received thrombolytic
      therapy, and more often had an inferior vena cava filter inserted. Major or
      intracranial bleeding was not different between groups. In-hospital all-cause
      death occurred in 8.4 and 5.9 % of patients with and without cancer,
      respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27-3.98; P =
      0.006) was an independent predictor of in-hospital death. Clinical instability,
      PE recurrence, age >=75 years, recent bed rest >=3 days, but not cancer, were
      independent predictors of in-hospital death due to PE. Cancer seems a weaker
      predictor of all-cause in-hospital death compared to other factors; the mere
      presence of cancer, without other risk factors, leads to a probability of early
      death of 2 %. In patients with acute PE, cancer increases the probability of in
      hospital all-cause death, but does not seem to affect the clinical presentation
      or the risk of in-hospital PE-related death. 

PMID- 27023067
TI  - Optical Coherence Tomography Angiography of Fibrosis in Age-Related Macular
      Degeneration.
AB  - PURPOSE: To describe the optical coherence tomography angiography (OCTA) features
      of subretinal fibrosis in the context of exudative age-related macular
      degeneration. METHODS: Patients diagnosed exudative age-related macular
      degeneration presenting with subretinal fibrosis were imaged by conventional
      multimodal imaging and OCTA. The patients were divided into the following two
      groups: group A, for eyes with active exudative features over the last 6 months,
      and group B, for eyes without any sign of exudation for >6 months. RESULTS: In
      almost all of the patients, a high-flow network was detected inside of the
      fibrotic scar. We divided the vascular networks into the following three
      patterns: the pruned vascular tree, tangled network and vascular loop patterns.
      Furthermore, two types of low-flow structures, for which we coined the terms
      large flow void and dark halo, were observed. Both active and inactive lesions
      demonstrated the abovementioned patterns either individually or together. No
      difference was found between the two groups in the prevalent vascular network
      pattern of low-flow areas. CONCLUSION: OCTA of subretinal fibrosis revealed a
      perfused, abnormal vascular network, as well as collateral architectural changes
      in the outer retina and the choriocapillaris layer, in the majority of the
      studied eyes. These features are associated with both active and inactive
      fibrotic choroidal neovessels.

PMID- 27023068
TI  - Copy Number Variations of the Azoospermia Factor Region and SRY Are Not
      Associated with the Risk of Hypospadias.
AB  - We investigated the frequency of copy number variations (CNVs) in the Y
      chromosome of Japanese children with hypospadias. We analyzed the copy number of
      the azoospermia factor (AZF) region and SRY, using multiplex ligation-dependent
      probe amplification. Four AZF-linked CNVs, including one novel simple
      duplication, were identified in 39 of 89 patients, at a frequency comparable to
      that of those in unaffected individuals. SRY-linked CNVs were absent in our
      patients. The results imply that CNVs in the AZF region and SRY are not
      associated with the risk of hypospadias in the Japanese population, although the
      pathogenicity of the AZF-linked simple duplication remains to be elucidated.

PMID- 27023069
TI  - Allicin Induces Calcium and Mitochondrial Dysregulation Causing Necrotic Death in
      Leishmania.
AB  - BACKGROUND: Allicin has shown antileishmanial activity in vitro and in vivo.
      However the mechanism of action underlying its antiproliferative effect against
      Leishmania has been virtually unexplored. In this paper, we present the results
      obtained in L.infantum and a mechanistic basis is proposed. METHODOLOGY/PRINCIPAL
      FINDING: Exposure of the parasites to allicin led to high Ca2+ levels and
      mitochondrial reactive oxygen species (ROS), collapse of the mitochondrial
      membrane potential, reduced production of ATP and elevation of cytosolic ROS. The
      incubation of the promastigotes with SYTOX Green revealed that decrease of ATP
      was not associated with plasma membrane permeabilization. Annexin V and propidium
      iodide (PI) staining indicated that allicin did not induce phospholipids exposure
      on the plasma membrane. Moreover, DNA agarose gel electrophoresis and TUNEL
      analysis demonstrated that allicin did not provoke DNA fragmentation. Analysis of
      the cell cycle with PI staining showed that allicin induced cell cycle arrest in
      the G2/M phase. CONCLUSIONS/SIGNIFICANCE: We conclude that allicin induces
      dysregulation of calcium homeostasis and oxidative stress, uncontrolled by the
      antioxidant defense of the cell, which leads to mitochondrial dysfunction and a
      bioenergetic catastrophe leading to cell necrosis and cell cycle arrest in the
      premitotic phase.

PMID- 27023070
TI  - Disparities in Treatment Uptake and Outcomes of Patients with Obesity in the USA.
AB  - There are clear and persistent disparities in obesity prevalence within the USA.
      Some of these disparities fall along racial/ethnic lines; however, there are a
      number of other social and demographic constructs where obesity disparities are
      present. In addition to differing rates of obesity across groups, there is
      growing evidence that subgroups of patients both seek out and respond to obesity
      treatment differently. This review article explores the epidemiology of obesity
      disparities, as well as the existing evidence around how different groups may
      respond to behavioral, medical, and surgical therapies, and potential reasons for
      differential uptake and response, from culture, to access, to physiology. We find
      that the vast majority of evidence in this area has focused on the observation
      that African Americans tend to lose less weight in clinical trials compared to
      non-Hispanic whites and mainly pertains to behavioral interventions. Moving
      forward, there will be a need for studies that broaden the notion of health
      disparity beyond just comparing African Americans and non-Hispanic whites.
      Additionally, a more thorough examination of the potential for disparate outcomes
      after medical and surgical treatments of obesity is needed, coupled with the
      careful study of possible physiologic drivers of differential treatment response.

PMID- 27023072
TI  - Palladium Mediated Rapid Deprotection of N-Terminal Cysteine under Native
      Chemical Ligation Conditions for the Efficient Preparation of Synthetically
      Challenging Proteins.
AB  - Facilitating the process of chemical protein synthesis is an important goal in
      order to enable the efficient preparation of large and novel protein analogues.
      Native chemical ligation, which is widely used in the synthesis and semisynthesis
      of proteins, has been going through several developments to expedite the
      synthetic process and to obtain the target protein in high yield. A key aspect of
      this approach is the utilization of protecting groups for the N-terminal Cys in
      the middle fragments, which bear simultaneously the two reactive groups, i.e., N
      terminal Cys and C-terminal thioester. Despite important progress in this area,
      as has been demonstrated in the use of thiazolidine protecting group in the
      synthesis of over 100 proteins, finding optimal protecting group(s) remains a
      challenge. For example, the thiazolidine removal step is very slow (>8 h), and in
      some cases the applied conditions lead to undesired side reactions. Here we show
      that water-soluble palladium(II) complexes are excellent reagents for the
      effective unmasking of thiazolidine, enabling its complete removal within 15 min
      under native chemical ligation conditions. Moreover, palladium is also able to
      rapidly remove propargyloxycarbonyl-protecting group from the N-terminal Cys in a
      similar efficiency. The utility of the new removal conditions for both protecting
      groups is exemplified in the rapid and efficient synthesis of Lys34-ubiquitinated
      H2B and for the first time neddlyated peptides derived from cullin1. The current
      approach expands the use of palladium in protein chemistry and should
      significantly facilitate the chemical and semisynthesis of synthetically
      challenging proteins from multiple fragments. 

PMID- 27023071
TI  - Effectiveness of Workplace Weight Management Interventions: a Systematic Review.
AB  - A systematic review was conducted of randomized trials of workplace weight
      management interventions, including trials with dietary, physical activity,
      environmental, behavioral, and incentive-based components. Main outcomes were
      defined as change in weight-related measures. Keywords related to weight
      management and workplace interventions were used to search relevant databases,
      and 23 eligible studies were reviewed in detail using a data extraction form and
      quality assessment checklist. The trials were conducted mainly in the USA and
      Europe, with four additional countries represented. Interventions were mostly
      multicomponent and were implemented in both sexes and in a range of employment
      categories. Intervention effectiveness appeared unrelated to region of the world
      and was highest in 6-12-month trials. The results ranged widely from clinically
      significant 8.8-kg weight loss in one trial to less effective than the control
      treatment in others. Some workplace interventions achieve clinically significant
      benefits, and further studies are needed to replicate those results in wider
      sociocultural and geographical contexts. 

PMID- 27023073
TI  - Constructing Hypothetical Risk Data from the Area under the ROC Curve: Modelling
      Distributions of Polygenic Risk.
AB  - BACKGROUND: Modeling studies using hypothetical polygenic risk data can be an
      efficient tool for investigating the effectiveness of downstream applications
      such as targeting interventions to risk groups to justify whether empirical
      investigation is warranted. We investigated the assumptions underlying a method
      that simulates risk data for specific values of the area under the receiver
      operating characteristic curve (AUC). METHODS: The simulation method constructs
      risk data for a hypothetical population based on the population disease risk, and
      the odds ratios and frequencies of genetic variants. By systematically varying
      the parameters, we investigated under what conditions AUC values represent unique
      ROC curves with unique risk distributions for patients and nonpatients, and to
      what extend risk data can be simulated for precise values of the AUC. RESULTS:
      Using larger number of genetic variants each with a modest effect, we observed
      that the distributions of estimated risks of patients and nonpatients were
      similar for various combinations of the odds ratios and frequencies of the risk
      alleles. Simulated ROC curves overlapped empirical curves with the same AUC.
      CONCLUSIONS: Polygenic risk data can be effectively and efficiently created using
      a simulation method. This allows to further investigate the potential
      applications of stratifying interventions on the basis of polygenic risk.

PMID- 27023074
TI  - Enhanced Luminance of Electrochemical Cells with a Rationally Designed Ionic
      Iridium Complex and an Ionic Additive.
AB  - Light-emitting electrochemical cells (LEECs) offer the potential for high
      efficiency operation from an inexpensive device. However, long turn-on times and
      low luminance under steady-state operation are longstanding LEEC issues. Here, we
      present a single-layer LEEC with a custom-designed iridium(III) complex and a
      lithium salt additive for enhanced device performance. These devices display
      reduced response times, modest lifetimes, and peak luminances as high as 5500
      cd/m(2), 80% higher than a comparable device from an unoptimized complex and 50%
      higher than the salt-free device. Improved device efficiency suggests that salt
      addition balances space charge effects at the interfaces. Extrapolation suggests
      favorable half-lives of 120 +/- 10 h at 1000 cd/m(2) and 3800 +/- 400 h at 100
      cd/m(2). Overall, complex design and device engineering produce competitive LEECs
      from simple, single-layer architectures. 

PMID- 27023075
TI  - Can paroxysmal hemicrania be bilateral? A case report.

PMID- 27023076
TI  - Association between FGF20 rs12720208 gene polymorphism and Parkinson's disease: a
      meta-analysis.
AB  - Previous studies have claimed the association of rs12720208 polymorphism in the
      fibroblast growth factor 20 (FGF20) gene with the increased risk of Parkinson's
      disease (PD), but results from the published data were controversial. The aim of
      our present meta-analysis was to estimate the overall association between FGF20
      rs12720208 polymorphism and the risk of PD. Case-control studies with sufficient
      data evaluating the association between rs12720208 C/T polymorphism and PD
      susceptibility were systematically identified in PubMed, OVID, SinoMed, Chinese
      National Knowledge Infrastructure (CNKI) up to July 10, 2015. A total of 3402 PD
      patients and 3739 controls from seven case-control studies were collected for
      this meta-analysis. The pooled odds ratio (OR) with its 95 % confidence interval
      (CI) was calculated to assess the genetic association between FGF20 rs12720208
      polymorphism and the risk of PD. In this study, no enough proof was found to
      prove the association in any genetic models with random-effects model (CT+TT vs.
      CC: OR = 1.147, 95 % CI: 0.883-1.489, P = 0.304; TT vs. CC+CT: OR = 1.754, 95 %
      CI: 0.878-3.505, P = 0.112; T vs. C: OR = 1.169, 95 % CI = 0.919-1.487, P =
      0.204; TT+CC vs. CT: OR = 0.906, 95 % CI = 0.694-1.182, P = 0.466). Our results
      suggest that there is no sufficient evidence to support the association between
      rs12720208 polymorphism and PD risk. Studies with larger sample size across
      diverse populations and subgroup analyses are necessary in the future. 

PMID- 27023078
TI  - Is it possible to be more productive in less time?

PMID- 27023077
TI  - The Phytophthora mating hormone alpha2 is an antagonist of the counterhormone
      alpha1.
AB  - The crop destroyer Phytophthora uses mating hormones alpha1 and alpha2 to
      commence its sexual reproduction. The alpha1-induced sexual reproduction of the
      A2 mating type was unexpectedly found to be interfered with by the counterhormone
      alpha2 that the A2 type itself produces to induce the sexual reproduction of the
      A1 type. A plausible mechanism is proposed based on structure-activity
      relationships. 

PMID- 27023079
TI  - Brown macule on the waist.

PMID- 27023080
TI  - Therapies to improve the cosmetic symptoms of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. The
      cosmetic symptoms of AD can have a serious impact on a patient's quality of life.
      Although there currently is no cure for AD, treatment is aimed at relieving its
      symptoms and preventing acute exacerbations as well as improving cosmetic
      appearance to enhance quality of life. The standard of care focuses on avoiding
      skin irritants and triggers along with the use of moisturizers; topical
      corticosteroids (TCs); topical calcineurin inhibitors (TCIs); and other
      treatments such as wet wraps, light therapy, and systemic immunomodulation
      therapies. 

PMID- 27023081
TI  - Diagnosing porokeratosis of Mibelli every time: a novel biopsy technique to
      maximize histopathologic confirmation.
AB  - Porokeratosis of Mibelli (PM) is a rare condition with the potential for
      malignant transformation that presents a clinical and pathologic diagnostic
      challenge. An improperly oriented biopsy may lead to the wrong histopathologic
      diagnosis. We report a case of PM that was previously misdiagnosed and describe a
      biopsy technique for suspected PM that maximizes the potential for
      histopathologic confirmation of the diagnosis. 

PMID- 27023082
TI  - Don't get hung up on fishhooks: a guide to fishhook removal.
AB  - In the sport of fishing, barbed fishhooks often are used for their effectiveness
      in maintaining the fish on the hook once it is caught. However, if a fishhook is
      implanted in the skin of a fisherman or fisherwoman, a barb can pose problems in
      removing the fishhook without exacerbating internal injury, a common fear among
      outpatient physicians. We describe the case of a patient who presented to the
      dermatology clinic with a barbed fishhook injury and discuss several simple
      methods for barbed fishhook removal that can be easily utilized in the outpatient
      setting. Because failing to treat the patient may lead to further discomfort and
      increased risk for complications, practitioners should be familiar with the
      removal methods described here, as they are not time consuming and do not require
      complex equipment. Furthermore, these techniques may be useful for removal of
      other foreign bodies embedded in cutaneous tissue (eg, splinters). 

PMID- 27023083
TI  - Prolonged pustular eruption from hydroxychloroquine: an unusual case of acute
      generalized exanthematous pustulosis.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption
      that often is a reaction to medications, most commonly antibiotics. Clinically,
      AGEP closely mimics pustular psoriasis and also is similar to subcorneal pustular
      dermatosis and IgA pemphigus. For clinicians, it is important to differentiate
      AGEP from pustular psoriasis. Acute generalized exanthematous pustulosis will
      have an acute drug association. Few cases have been known to be caused by
      hydroxychloroquine (HCQ). Proper therapeutic management of AGEP includes
      withdrawal of the offending agent, and resolution typically occurs within 15
      days. We report a case of AGEP after HCQ administration that did not follow the
      usual course of resolution after medication cessation. The patient continued to
      experience cutaneous eruptions that waxed and waned for 81 days.
      Hydroxychloroquine has a particularly long half-life and is a known cause of
      AGEP; therefore, it is possible that HCQ-induced AGEP may not follow the typical
      rapid recovery time. 

PMID- 27023084
TI  - Radiation-induced pemphigus or pemphigoid disease in 3 patients with distinct
      underlying malignancies.
AB  - The cutaneous lesions of radiation-induced pemphigus or pemphigoid disease may
      resemble other skin diseases, including recurrent underlying cancer. We performed
      a computerized search of Mayo Clinic (Rochester, Minnesota) archives and
      identified 3 cases of pemphigus or pemphigoid disease that occurred after
      radiation therapy for breast, cervical, and metastatic malignancies,
      respectively. In 2 of these patients, the disease was initially confined to the
      irradiated field but subsequently disseminated to other parts of the patients'
      bodies, including mucosal surfaces. In all 3 patients, the blistering disease
      occurred 5 to 14 months after the onset of radiation therapy. All 3 were treated
      with corticosteroids and demonstrated complete recovery of the skin eruption
      after radiotherapy was discontinued. Although the precise mechanism of this
      cutaneous eruption is unknown, clinicians should be alert for this potentially
      serious complication and evaluate all cutaneous eruptions developing during and
      after radiotherapy. 

PMID- 27023085
TI  - Diet and atopic dermatitis.
AB  - Dermatologists and pediatric dermatologists frequently treat patients with atopic
      dermatitis (AD), and patients and guardians often associate AD with food
      allergies. A common misconception is that dietary restrictions will resolve the
      disease. The role of diet is evolving in the discussion of AD. The American
      Academy of Dermatology (AAD) has recently provided recommendations on diet and
      therapies for AD. This article reviews recent scientific data on the role of
      foods and dietary modifications in the management of AD as both an intervention
      and as prevention. 

PMID- 27023086
TI  - Effects of tumor necrosis factor alpha inhibitors extend beyond psoriasis:
      insulin sensitivity in psoriasis patients with type 2 diabetes mellitus.
AB  - Psoriasis is a chronic inflammatory disease that has been associated with an
      increased incidence of insulin resistance and diabetes mellitus (DM). Tumor
      necrosis factor (TNF) alpha inhibitors and IL-6 blockers, which are routinely
      used for the treatment of psoriasis, have been positively associated with insulin
      sensitivity. The aim of this study was to assess the effects of treatment with
      TNF-alpha inhibitors on insulin sensitivity in psoriatic patients with type 2 DM.
      This study confirms a beneficial effect of anti-TNF-alpha agents on insulin
      resistance and insulin sensitivity in psoriasis patients with type 2 DM. 

PMID- 27023087
TI  - Multiple superficial white nodules on the bilateral helical rims.

PMID- 27023088
TI  - Clinical pearl: the squeeze maneuver.
AB  - Plantar warts can be distinguished from calluses using the squeeze maneuver, a
      quick and easy method to diagnose plantar warts. This technique negates the need
      for an expensive diagnostic tool. 

PMID- 27023089
TI  - Non-drug-induced pemphigus foliaceus in a patient with rheumatoid arthritis.

PMID- 27023090
TI  - Night of the living thrips: an unusual outbreak of Thysanoptera dermatitis.
AB  - Identifying the etiology of a cutaneous eruption in the setting of an acute
      cluster outbreak is of utmost importance due to the inherent potential public
      health impact. The differential diagnosis ranges from innocuous arthropod bites
      to more concerning causes such as infection, medication reaction, and
      environmental exposure. We report the simultaneous presentation of 15 US Marines
      who presented with numerous discrete papular skin eruptions. Subsequent thorough
      patient evaluation and history, literature review, immunization status
      reconciliation, entomological assessment, site survey, and skin biopsy were
      performed. This case series is one of the largest reported to date of a cluster
      outbreak of a papular dermatitis secondary to bites from thrips (ie, insects of
      the order Thysanoptera). 

PMID- 27023091
TI  - Cyclosporine in SJS/TEN management: a brief review.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are
      considered to be among the most severe dermatologic emergencies with high risk
      for morbidity and mortality if managed poorly. These disease processes usually
      are the result of a reaction to antipsychotic or antibiotic medications, though
      the complete list of potential causative drugs is extensive. Despite the life
      threatening nature of these conditions, studies evaluating systemic
      immunomodulating agents that would be effective in halting the poor overall
      outcome are limited. Over the last several years, reports advocating the benefits
      of cyclosporine, corticosteroids, and intravenous immunoglobulin (IVIG) have
      shown variable responses in their treatment of SJS/TEN. In this article,
      cyclosporine and its potential as an emerging therapeutic option for SJS/TEN
      patients is discussed. 

PMID- 27023092
TI  - An eruption while on total parenteral nutrition.

PMID- 27023093
TI  - Confluent erythematous plaques on the palm.

PMID- 27023094
TI  - Necrotizing cellulitis with multiple abscesses on the leg caused by Serratia
      marcescens.
AB  - Serratia marcescens is an unusual cause of severe skin infection initially
      described in immunocompromised patients. We report a case of necrotizing
      cellulitis of the leg caused by S marcescens in a 68-year-old woman with diabetes
      mellitus and a history of chronic lymphoedema of the leg. We reviewed the
      literature and found 49 cases of severe skin infections from S marcescens that
      included 20 cases of necrotizing fasciitis (NF) as well as 29 cases of severe
      skin infections without NF (non-NF cases). Patients were immunocompromised in 59%
      to 70% of cases. The mortality rate was high in NF cases (60%) versus non-NF
      cases (3%). Surgery was required in 95% of NF cases and in 24% of non-NF cases.
      The other clinical manifestations of S marcescens skin infection reported in the
      literature included disseminated papular eruptions in patients infected with
      human immunodeficiency virus with folliculitis on the trunk. Serratia marcescens
      is naturally resistant to amoxicillin alone and amoxicillin associated with
      clavulanic acid. Broad-spectrum antibiotics are indicated to treat S marcescens
      skin infections, and surgery should be promptly considered in cases of severe
      skin infections if appropriate antibiotic therapy does not lead to rapid
      improvement. 

PMID- 27023095
TI  - Integrative NMR for biomolecular research.
AB  - NMR spectroscopy is a powerful technique for determining structural and
      functional features of biomolecules in physiological solution as well as for
      observing their intermolecular interactions in real-time. However, complex steps
      associated with its practice have made the approach daunting for non-specialists.
      We introduce an NMR platform that makes biomolecular NMR spectroscopy much more
      accessible by integrating tools, databases, web services, and video tutorials
      that can be launched by simple installation of NMRFAM software packages or using
      a cross-platform virtual machine that can be run on any standard laptop or
      desktop computer. The software package can be downloaded freely from the NMRFAM
      software download page ( http://pine.nmrfam.wisc.edu/download_packages.html ),
      and detailed instructions are available from the Integrative NMR Video Tutorial
      page ( http://pine.nmrfam.wisc.edu/integrative.html ).

PMID- 27023096
TI  - Bio-inspired feedback-circuit implementation of discrete, free energy optimizing,
      winner-take-all computations.
AB  - Bayesian inference and bounded rational decision-making require the accumulation
      of evidence or utility, respectively, to transform a prior belief or strategy
      into a posterior probability distribution over hypotheses or actions. Crucially,
      this process cannot be simply realized by independent integrators, since the
      different hypotheses and actions also compete with each other. In continuous
      time, this competitive integration process can be described by a special case of
      the replicator equation. Here we investigate simple analog electric circuits that
      implement the underlying differential equation under the constraint that we only
      permit a limited set of building blocks that we regard as biologically
      interpretable, such as capacitors, resistors, voltage-dependent conductances and
      voltage- or current-controlled current and voltage sources. The appeal of these
      circuits is that they intrinsically perform normalization without requiring an
      explicit divisive normalization. However, even in idealized simulations, we find
      that these circuits are very sensitive to internal noise as they accumulate error
      over time. We discuss in how far neural circuits could implement these operations
      that might provide a generic competitive principle underlying both perception and
      action.

PMID- 27023097
TI  - There is no simple lateral ankle sprain.

PMID- 27023098
TI  - Anatomy of the inferior extensor retinaculum and its role in lateral ankle
      ligament reconstruction: a pictorial essay.
AB  - The inferior extensor retinaculum (IER) is an aponeurotic structure, which is in
      continuation with the anterior part of the sural fascia. The IER has often been
      used to augment the reconstruction of the lateral ankle ligaments, for instance
      in the Brostrom-Gould procedure, with good outcomes reported. However, its
      anatomy has not been described in detail and only a few studies are available on
      this structure. The presence of a non-constant oblique supero-lateral band
      appears to be important. This structure defines whether the augmentation of the
      lateral ankle ligaments reconstruction is performed using true IER or only the
      anterior part of the sural fascia. It is concluded that the use of this structure
      will have an impact on the resulting ankle stability. 

PMID- 27023099
TI  - PhoB activation in non-limiting phosphate condition by the maintenance of high
      polyphosphate levels in the stationary phase inhibits biofilm formation in
      Escherichia coli.
AB  - Polyphosphate (polyP) degradation in Escherichia coli stationary phase triggers
      biofilm formation via the LuxS quorum sensing system. In media containing excess
      of phosphate (Pi), high polyP levels are maintained in the stationary phase with
      the consequent inhibition of biofilm formation. The transcriptional-response
      regulator PhoB, which is activated under Pi limitation, is involved in the
      inhibition of biofilm formation in several bacterial species. In the current
      study, we report, for the first time, we believe that E. coli PhoB can be
      activated in non-limiting Pi conditions, leading to inhibition of biofilm
      formation. In fact, PhoB was activated when high polyP levels were maintained in
      the stationary phase, whereas it remained inactive when the polymer was degraded
      or absent. PhoB activation was mediated by acetyl phosphate with the consequent
      repression of biofilm formation owing to the downregulation of c-di-GMP synthesis
      and the inhibition of autoinducer-2 production. These results allowed us to
      propose a model showing that PhoB is a component in the signal cascade regulating
      biofilm formation triggered by fluctuations of polyP levels in E. coli cells
      during stationary phase.

PMID- 27023100
TI  - Cells of Benign and Borderline Thyroid Tumor Express Malignancy Markers.
AB  - We studied expression of malignancy markers galectin-3, cytokeratin-19, HBME-1,
      fibronectin, and cyclin D1 in cells of benign (n=51), malignant (n=87), and
      borderline (n=53) tumors. The results indicate that 3.9% benign and 41.5%
      borderline tumors express malignancy markers (specificity 98-100%). Follow up
      over 1-10 years after surgical treatment for borderline tumors showed no
      progression of tumor growth. We conclude that some benign and borderline tumors
      represent low-grade neoplasms with favorable prognosis. 

PMID- 27023101
TI  - Erratum to: The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed
      Genetic Journey--ADNP Mutation.

PMID- 27023102
TI  - Histopathology of the Human Inner Ear in the p.L114P COCH Mutation (DFNA9).
AB  - The histopathology of the inner ear in a patient with hearing loss caused by the
      p.L114P COCH mutation and its correlation with the clinical phenotype are
      presented. To date, 23 COCH mutations causative of DFNA9 autosomal dominant
      sensorineural hearing loss and vestibular disorder have been reported, and the
      histopathology of the human inner ear has been described in 4 of these. The
      p.L114P COCH mutation was first described in a Korean family. We have identified
      the same mutation in a family of non-Asian ancestry in the USA, and the temporal
      bone histopathology and clinical findings are presented herein. The
      histopathology found in the inner ear was similar to that shown in the 4 other
      COCH mutations and included degeneration of the spiral ligament with deposition
      of an eosinophilic acellular material, which was also found in the distal osseous
      spiral lamina, at the base of the spiral limbus, and in mesenchymal tissue at the
      base of the vestibular neuroepithelium. This is the first description of human
      otopathology of the COCH p.L114P mutation. In addition, it is the only case with
      otopathology characterization in an individual with any COCH mutation and
      residual hearing, thus allowing assessment of primary histopathological events in
      DFNA9, before progression to more profound hearing loss. A quantitative cytologic
      analysis of atrophy in this specimen and immunostaining using anti-neurofilament
      and anti-myelin protein zero antibodies confirmed that the principal
      histopathologic correlate of hearing loss was degeneration of the dendritic
      fibers of spiral ganglion cells in the osseous spiral lamina. The implications
      for cochlear implantation in this disorder are discussed. 

PMID- 27023103
TI  - Accurate prediction tools in prostate cancer require consistent assessment of
      included variables.
AB  - OBJECTIVE: The aim of this study was to create a preoperative prediction model
      predicting extraprostatic tumour growth in men with clinically organ-confined
      disease from a prospectively collected Swedish cohort. MATERIALS AND METHODS: The
      study used data from 3386 men in the prospective multi-centre Laparoscopic
      Prostatectomy Robot Open (LAPPRO) trial, with 14 participating urological
      departments. External validation was performed using a cohort of 634 men from the
      largest study centre with patients who underwent surgery before and after the
      inclusion period of the LAPPRO study. External validation of the updated Partin
      table was used for comparison. The prediction models were created by
      multivariable logistic regression. Nomogram prediction performance, internal,
      internal-external and external validation are presented as the area under the
      receiver operating characteristic curve (AUC). RESULTS: The nomogram reached a
      prediction performance with an AUC of 0.741, with internal and external
      validation of 0.738 and 0.698, respectively. Internal-external validation showed
      great divergence between centres, with AUCs ranging from 0.476 to 0.892,
      indicating inconsistencies in pathological staging or one or more of the included
      variables in the regression model. When including centre as a variable in the
      multivariable model it was significantly associated with the outcome of pT3 (p <
      0.001). AUC for external validation of the Partin table was 0.694. CONCLUSIONS:
      Accurate prediction tools in prostate cancer require consistent assessment of
      included variables, and local validation is needed before the use of such tools
      in clinical practice.

PMID- 27023104
TI  - Catastrophic antiphospholipid syndrome in pregnancy, a diagnosis that should not
      be missed.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is an accelerated form of the
      antiphospholipid antibody syndrome resulting in multi-organ ischemia and failure.
      It is a rare and life-threatening condition that can be easily mistaken with
      hemolysis elevated liver enzymes low platelets syndrome, thrombotic
      thrombocytopenic purpura, and hemolytic uremic syndrome. In order to make a
      diagnosis, it is required to have multi-organ thrombosis over 1 week affecting at
      least three organs or systems, and to have positive antiphospholipid antibody on
      two occasions (6 weeks apart), and histopathologic confirmation of small vessel
      occlusion. However, due to similarities in clinical and laboratory findings
      between CAPS and some other obstetric complications, potential misdiagnosis or
      delay in diagnosis are common, increasing the risk of adverse maternal and
      perinatal outcomes. In this review we summarized information presented in
      previous studies, focusing on CAPS related to pregnancy. We reviewed diagnostic
      criteria, differential diagnosis, and common presentation ranging from malaise,
      abdominal pain, dyspnea, hypertension, to altered mental status and seizures. We
      also discussed management in pregnancy and included a detailed algorithm with
      steps to take. Of note, the most significant reduction in mortality was seen in
      patients receiving triple therapy which will be discussed in this review. 

PMID- 27023105
TI  - Comparative, open-label prospective study on the quality of life and sexual
      function of women affected by endometriosis-associated pelvic pain on 2 mg
      dienogest/30 ug ethinyl estradiol continuous or 21/7 regimen oral contraceptive.
AB  - PURPOSE: To evaluate the effects of a continuous regimen combined oral
      contraceptive (COC) containing 2 mg dienogest and 30 ug ethinyl estradiol
      (DNG/EE) compared to a 21/7 regimen on the quality of life (QoL) and sexual
      function in women affected by endometriosis-associated pelvic pain. METHODS:
      Sixty-three women constituted the Study group treated with DNG/EE COC continuous
      regimen; 33 women were given DNG/EE COC in a 21/7 regimen. To define the
      endometriosis-associated pelvic pain, the Visual Analogic Scale was used. The
      Short Form-36, Female Sexual Function Index (FSFI) and the Female Sexual Distress
      Scale (FSDS) were used to assess QoL, sexual function and sexual distress,
      respectively. The study included two follow-ups. RESULTS: At 3 and 6 months of
      treatment there was an improvement in pain of the Study group (p < 0.001). The
      Control group underwent pain improvement at the second follow-up (p < 0.05). At
      the first and the second follow-ups, the Study group reported QoL improvements in
      all categories (p < 0.001). The Control group reported QoL improvements in all
      categories at the second follow-up (p < 0.05). At the first and the second follow
      ups of the Study group, the FSFI total score had risen (p < 0.001), and the FSDS
      score had dropped (p < 0.001). An improvement of the FSFI score and a reduction
      of the FSDS score of the Control group was observed at the second follow-up (p <
      0.001), but not at the first follow-up (p = NS). CONCLUSIONS: Women on DNG/EE COC
      continuous regimen reported a reduction of endometriosis-associated pelvic pain
      and there was an improvement of their sexual activity and their QoL that was
      better than the DNG/EE 21/7 conventional regimen.

PMID- 27023106
TI  - The relationship between visfatin and serum concentrations of C-reactive protein,
      interleukin 6 in patients with metabolic syndrome.
AB  - AIM: To evaluate the relationship between inflammatory and pro inflammatory
      markers, with obesity and visceral adiposity in male subjects with or without
      metabolic syndrome (MS). SUBJECTS AND METHODS: A total of 37 patients with MS and
      37 age matched controls were included (mean age 46.35 +/- 1.6 years). MS was
      defined by the criteria of the international diabetes federation 2005.
      Anthropometric and biochemical profiles, including high-sensitivity C-reactive
      protein (Hs-CRP), visfatin and interleukin 6 (IL-6), were measured. Data were
      compared between groups by using t test. Pearson's correlation was used to
      evaluate the relationship between variables. P values less than 0.05 were
      considered as statistically significant. RESULTS: In patients with MS, CRP and IL
      6 were significantly correlated with body mass index, waist circumference and
      waist to hip ratio. Visfatin levels were significantly lower in patients with MS
      compared to controls (log visfatin: 1.74 +/- 0.27 vs. 1.86 +/- 0.13 ng/ml, MS vs.
      control group respectively). We cannot find any significant correlation between
      visfatin, CRP and IL-6. Also there were no correlation between visfatin levels
      and any anthropometric parameters in patients with MS or control groups.
      CONCLUSION: Serum visfatin was lower in patients with MS. Therefore it seems that
      visfatin could not be considered as a pro inflammatory adipocytokine in MS. The
      positive associations of obesity and visceral adiposity with elevated CRP and IL
      6 levels suggest the importance of reducing visceral adiposity to prevent the
      risk of coronary disease.

PMID- 27023108
TI  - Swept-Source Optical Coherence Tomography AngioTM (Topcon Corp, Japan):
      Technology Review.
AB  - Optical coherence tomography (OCT) angiography (OCTA) is a novel, noninvasive,
      three-dimensional imaging technique that allows for the visualization of
      intravascular flow in the microvasculature. Swept-source OCT technology utilizes
      longer-wavelength infrared light than conventional spectral-domain OCT. This
      enables improved penetration into tissue and imaging through optical opacities
      and is invisible to the subject. Topcon has recently developed an innovative OCTA
      algorithm, OCTARA (OCTA Ratio Analysis), which benefits from being paired with
      swept-source OCT. OCTARA aims to provide improved detection sensitivity of low
      blood flow and reduced motion artifacts without compromising axial resolution. In
      this chapter, we describe the implementation of OCTARA with swept-source OCT
      technology, the technical specifications of acquisition (e.g. the number of
      scans, area of examination field, etc.) along with the algorithm's function and
      principles for analysis of B-scan data to achieve angiographic visualization.
      Examples of OCTA scans performed using the OCTARA algorithm and a comparison of
      these scans with images obtained using other technologies are also presented. 

PMID- 27023107
TI  - High temperature specifically affects the photoprotective responses of
      chlorophyll b-deficient wheat mutant lines.
AB  - The effects of high temperature on CO2 assimilation rate, processes associated
      with photosynthetic electron and proton transport, as well as photoprotective
      responses, were studied in chlorophyll b-deficient mutant lines (ANK-32A and ANK
      32B) and wild type (WT) of wheat (Triticum aestivum L.). Despite the low
      chlorophyll content and chlorophyll a-to-b ratio, the non-stressed mutant plants
      had the similar level of CO2 assimilation and photosynthetic responses as WT.
      However, in ANK mutant plants exposed to prolonged high temperature episode (42 
      degrees C for ~10 h), we observed lower CO2 assimilation compared to WT,
      especially when a high CO2 supply was provided. In all heat-exposed plants, we
      found approximately the same level of PSII photoinhibition, but the decrease in
      content of photooxidizable PSI was higher in ANK mutant plants compared to WT.
      The PSI damage can be well explained by the level of overreduction of PSI
      acceptor side observed in plants exposed to high temperature, which was, in turn,
      the result of the insufficient transthylakoid proton gradient associated with low
      non-photochemical quenching and lack of ability to downregulate the linear
      electron transport to keep the reduction state of PSI acceptor side low enough.
      Compared to WT, the ANK mutant lines had lower capacity to drive the cyclic
      electron transport around PSI in moderate and high light; it confirms the
      protective role of cyclic electron transport for the protection of PSI against
      photoinhibition. Our results, however, also suggest that the inactivation of PSI
      in heat stress conditions can be the protective mechanism against photooxidative
      damage of chloroplast and cell structures.

PMID- 27023109
TI  - Knocking Down TMPRSS2-ERG Fusion Oncogene by siRNA Could be an Alternative
      Treatment to Flutamide.
AB  - Our purpose was to develop a new pharmacological approach for the treatment of
      prostate cancer (PCa), the most common neoplasia in men. Recently, we developed
      siRNA against the fusion oncogene TMPRSS2-ERG found in 50% of patients and showed
      an antitumoral activity in animal model. Herein, we want to compare or combine
      the developed siRNA to flutamide (FLU), one of the gold-standard treatment of
      PCa. Therefore, concomitant or subsequent association of FLU to siRNA TMPRSS2-ERG
      was performed in VCaP cells and in SCID mice bearing xenografted VCaP tumors.
      ERG, androgen receptor, cleaved-caspase-3 as well as phase 1 and 2 drug
      metabolizing enzymes were investigated within tumors. We observed similar results
      in terms of TMPRSS2-ERG knock-down and cell viability impairment for all distinct
      schedules of administration. The association of siRNA TMPRSS2-ERG-squalene
      nanoparticles with flutamide displayed similar tumor growth inhibition as mice
      treated with siRNA TMPRSS2-ERG-squalene nanoparticles alone and was paralleled
      with modification of expression of ERG, androgen receptor, and cleaved-caspase-3.
      Phase 1 and 2 enzymes were essentially affected by FLU and reverted when combined
      with squalenoylated siRNA. In conclusion, these results confirm the therapeutic
      effectiveness of squalenoyl siRNA nanomedicine for PCa based on siRNA TMPRSS2
      ERG. 

PMID- 27023110
TI  - A Pressure Injection System for Investigating the Neuropharmacology of
      Information Processing in Awake Behaving Macaque Monkey Cortex.
AB  - The top-down modulation of feed-forward cortical information processing is
      functionally important for many cognitive processes, including the modulation of
      sensory information processing by attention. However, little is known about which
      neurotransmitter systems are involved in such modulations. A practical way to
      address this question is to combine single-cell recording with local and
      temporary neuropharmacological manipulation in a suitable animal model. Here we
      demonstrate a technique combining acute single-cell recordings with the injection
      of neuropharmacological agents in the direct vicinity of the recording electrode.
      The video shows the preparation of the pressure injection/recording system,
      including preparation of the substance to be injected. We show a rhesus monkey
      performing a visual attention task and the procedure of single-unit recording
      with block-wise pharmacological manipulations. 

PMID- 27023111
TI  - Zinc(II)-Thiosemicarbazone Complexes Are Localized to the Lysosomal Compartment
      Where They Transmetallate with Copper Ions to Induce Cytotoxicity.
AB  - As the di-2-pyridylketone thiosemicarbazone (DpT) and 2-acetylpyridine
      thiosemicarbazone (ApT) series show potent antitumor activity in vitro and in
      vivo, we synthesized their fluorescent zinc(II) complexes to assess their
      intracellular distribution. The Zn(II) complexes generally showed significantly
      greater cytotoxicity than the thiosemicarbazones alone in several tumor cell
      types. Notably, specific structure-activity relationships demonstrated the
      importance of the di-2-pyridyl pharmacophore in their activity. Confocal
      fluorescence imaging and live cell microscopy showed that the Zn(II) complex of
      our lead compound, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
      (DpC), which is scheduled to enter clinical trials, was localized to lysosomes.
      Under lysosomal conditions, the Zn(II) complexes were shown to transmetallate
      with copper ions, leading to redox-active copper complexes that induced lysosomal
      membrane permeabilization (LMP) and cytotoxicity. This is the first study to
      demonstrate direct lysosomal targeting of our novel Zn(II)-thiosemicarbazone
      complexes that mediate their activity via transmetalation with copper ions and
      LMP.

PMID- 27023112
TI  - Invoking Direct Exciton-Plasmon Interactions by Catalytic Ag Deposition on Au
      Nanoparticles: Photoelectrochemical Bioanalysis with High Efficiency.
AB  - In this work, direct exciton-plasmon interactions (EPI) between CdS quantum dots
      (QDs) and Ag nanoparticles (NPs) were invoked ingeniously by catalytic Ag
      deposition on Au NPs for the stimulation of high efficient damping effect toward
      the excitonic responses in CdS QDs, on the basis of which a novel
      photoelectrochemical (PEC) bioanalytical format was achieved for sensitive
      microRNA detection. Specifically, upon the configurational change from the
      hairpin probe DNA to the "Y"-shaped ternary conjugate consisting of the original
      probe DNA, assistant DNA, and the target microRNA, the alkaline phosphatase (ALP)
      catalytic chemistry would then trigger the transition of the interparticle
      interplay from the CdS QDs-Au NPs to the CdS QDs-Ag NPs systems for the microRNA
      detection due to the dependence of the photocurrent quenching on the target
      concentration. This work not only provided a unique method for EPI generation
      among the PEC nanosystems but also offered a versatile and general protocol for
      future PEC bioanalysis development. 

PMID- 27023114
TI  - [In Process Citation].

PMID- 27023115
TI  - Characterization of Anisotropic Leaky Mode Modulators for Holovideo.
AB  - Holovideo displays are based on light-bending spatial light modulators. One such
      spatial light modulator is the anisotropic leaky mode modulator. This modulator
      is particularly well suited for holographic video experimentation as it is
      relatively simple and inexpensive to fabricate. Some additional advantages of
      leaky mode devices include: large aggregate bandwidth, polarization separation of
      signal light from noise, large angular deflection and frequency control of color.
      In order to realize these advantages, it is necessary to be able to adequately
      characterize these devices as their operation is strongly dependent on waveguide
      and transducer parameters. To characterize the modulators, the authors use a
      commercial prism coupler as well as a custom characterization apparatus to
      identify guided modes, calculate waveguide thickness and finally to map the
      device's frequency input and angular output of leaky mode modulators. This work
      gives a detailed description of the measurement and characterization of leaky
      mode modulators suitable for full-color holographic video.

PMID- 27023113
TI  - Long-Term Effects of (-)-Epigallocatechin Gallate (EGCG) on Pristane-Induced
      Arthritis (PIA) in Female Dark Agouti Rats.
AB  - Rheumatoid arthritis (RA)--a widespread chronic inflammatory disease in
      industrialized countries--is characterized by a persistent and progressive joint
      destruction. The chronic pro-inflammatory state results from a mutual activation
      of the innate and the adaptive immune system, while the exact pathogenesis
      mechanism is still under discussion. New data suggest a role of the innate immune
      system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only
      during onset and the destructive phase of RA but also at the chronification of
      the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a
      peroxidase strongly abundant in neutrophils, may be important: While its
      peroxidase activity is known to contribute to cartilage destruction at later
      stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also
      discussed for certain anti-inflammatory effects. In this study we used pristane
      induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of
      RA in man. We were able to shown that a specific detection of the HOCl-producing
      MPO activity provides a sensitive new marker to evaluate the actual systemic
      inflammatory status which is only partially detectable by the evaluation of
      clinical symptoms (joint swelling and redness measurements). Moreover, we
      evaluated the long-term pharmacological effect of the well-known anti
      inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early
      and continuous oral application of this polyphenol the arthritic symptoms were
      considerably diminished both in the acute and in the chronic phase of the
      disease. The obtained results were comparable to the treatment control
      (application of methotrexate, MTX). As revealed by stopped-flow kinetic
      measurements, EGCG may regenerate the HOCl-production of MPO which is known to be
      impaired at chronic inflammatory diseases like RA. It can be speculated that this
      MPO activity-promoting effect of EGCG may contribute to the pharmacological mode
      of action of this polyphenol.

PMID- 27023116
TI  - Image-based Multilevel Subdivision of M1 Category in TNM Staging System for
      Metastatic Nasopharyngeal Carcinoma.
AB  - Purpose To establish an image-based M1 category subdivision system for
      personalized prognosis prediction and treatment planning in patients with
      metastatic nasopharyngeal carcinoma (NPC). Materials and Methods A total of 1172
      patients with metachronous metastasic NPC were retrospectively enrolled (the
      dataset is from Sun Yat-sen University Cancer Center for derivation, and the
      combined datasets are from Guangzhou Medical University Cancer Center and the
      Fifth Affiliated Hospital of Sun Yat-sen University for validation). The Ethics
      Committee of the three centers approved this study. A general subdivision system
      of the M1 category was established on the basis of the most influential
      metastatic features for overall survival (OS). The following multilevel
      subdivision system for precise subdivision of the M1 category was designed: M
      [number of locations]-Location [number of lesions], with B indicating bone, L
      indicating the lung, H indicating the liver, and N indicating a node. The
      correlation of the M1 subdivisions with OS was determined with Cox regression.
      The best treatment response was assessed with Response Evaluation Criteria in
      Solid Tumors 1.1 guidelines and modified Response Evaluation Criteria in Solid
      Tumors criteria. Results Multivariate analysis in the derivation cohort showed
      that the number of metastatic lesions (multiple or single), the number of
      metastatic locations (multiple or single), liver involvement, and bone
      involvement were independent prognostic factors for OS. In general, subdividing
      the cohort by the number of metastatic lesions and the number of metastatic
      locations resulted in three subcategories of differential OS: M1a, a single
      lesion in a single organ or location; M1b, multiple lesions in a single organ or
      location; and M1c, metastases in multiple locations (for M1b vs M1a, hazard ratio
      [HR] = 2.28, 95% confidence interval [CI]: 1.71, 3.05; for M1c vs M1a, HR = 3.65,
      95% CI: 2.75, 4.85); these subdivisions were externally validated. The multilevel
      subdivision system could be further used to discriminate among subgroups of
      differential OS under the M1b subcategory. Findings from analysis of multilevel
      subgroups suggested that patients with a single metastatic lesion (M1-B1, M1-L1,
      M1-H1, M1-N1) or two lesions in the liver only (M1-H2) had high rates of complete
      response (CR) or complete surgical resection (CSR) and 3-year OS after treatment
      (CR plus CSR rates >30%, and 3-year OS rates >50%); there were high 3-year OS
      rates (>50%) in patients with stage M1-B2, M1-L2, or M1-H3 disease but relatively
      low rates of CR or CSR. Conclusion Use of the multilevel M1 subdivision system in
      patients with NPC could facilitate more precise prognosis prediction and better
      identification of patients who will respond well to treatment than the
      conventional subdivision strategy. ((c)) RSNA, 2016 Online supplemental material
      is available for this article.

PMID- 27023117
TI  - Abandoned metal mines and their impact on receiving waters: A case study from
      Southwest England.
AB  - Historic mine sites are a major source of contamination to terrestrial and river
      environments. To demonstrate the importance of determining the significance of
      point and diffuse metal contamination and the related bioavailability of the
      metals present from abandoned mines a case study has been carried out. The study
      provides a quantitative assessment of a historic mine site, Wheal Betsy,
      southwest England, and its contribution to non-compliance with Water Framework
      Directive (WFD) Environmental Quality Standards (EQS) for Cd, Cu, Pb and Zn.
      Surface water and sediment samples showed significant negative environmental
      impacts even taking account of the bioavailability of the metal present, with
      lead concentration in the stream sediment up to 76 times higher than the Canadian
      sediment guidelines 'Probable Effect Level'. Benthic invertebrates showed a
      decline in species richness adjacent to the mine site with lead and cadmium the
      main cause. The main mine drainage adit was the single most significant source of
      metal (typically 50% of metal load from the area, but 88% for Ni) but the mine
      spoil tips north and south of the adit input added together discharged roughly an
      equivalent loading of metal with the exception of Ni. The bioavailability of
      metal in the spoil tips exhibited differing spatial patterns owing to varying
      ambient soil physico-chemistry. The data collected is essential to provide a
      clear understanding of the contamination present as well as its mobility and
      bioavailability, in order to direct the decision making process regarding
      remediation options and their likely effectiveness.

PMID- 27023118
TI  - Transportation and localization of phenanthrene and its interaction with
      different species of arsenic in Pteris vittata L.
AB  - The interaction between arsenic (As) and phenanthrene (PHE) in Pteris vittata L.
      was investigated in this study. The migration and occurrence of PHE in P. vittata
      were determined by two-photon laser scanning confocal microscopy. Data indicated
      that PHE supplementation lowers the As concentration in P. vittata, decreasing As
      levels by 16.8-39.9% in the pinnae, 30.0-49.0% in the rachis, and 45-51.5% in the
      roots, respectively. Different arsenic species inhibited P. vittata PHE
      absorption. The most significant effect was observed using dimethylarsenic acid
      (DMA), which decreased PHE accumulation by 20.73%. With the exception of elevated
      As(V) concentrations in As(III)-treated plants, PHE treatment significantly
      reduced inorganic As concentrations in P. vittata. However, PHE elevated root DMA
      concentrations by 9%. According to in situ visualization, PHE is primarily found
      in the upper and lower epidermis and stomatal cells, particularly the stomata
      guard cells.

PMID- 27023119
TI  - Association of polycyclic aromatic hydrocarbons in housewives' hair with
      hypertension.
AB  - The relationship between polycyclic aromatic hydrocarbons (PAHs) and hypertension
      remains a subject of debate. The aims of this study were to determine an
      association of concentrations of PAHs in housewives' hair with hypertension risk
      and the modification effect of single nucleotide polymorphisms (SNPs) related to
      Phase I metabolism of PAHs. We recruited 405 women for a cross-sectional study in
      Shanxi Province, China, including 170 with hypertension (the case group) and 235
      without hypertension (the control group). We analyzed 26 individual PAHs in hair
      samples and the SNPs of the genes including cytochrome P450, family 1, subfamily
      A, polypeptide 1 (CYP1A1), CYP1A2, CYP1B1 and CYP2E1. Our results showed that
      seven PAHs in hair samples were measured with detection rate >70%. Only
      acenaphthylene was found to be associated with an increased risk of hypertension
      with adjustment for the potential confounders following Bonferroni correction,
      whereas others not. No SNPs of the concerned genes were found to be associated
      with the risk of hypertension. A multiple interaction effect of PAHs in
      housewives' hair and SNPs on hypertension risk was not observed. It was concluded
      that PAHs tended to contribute to the formation of hypertension.

PMID- 27023120
TI  - Uptake and effect of highly fluorescent silver nanoclusters on Scenedesmus
      obliquus.
AB  - The release of silver nanoparticles (Ag NPs) in aquatic environment has caused
      wide public concern about their effects on living organisms (e.g., algae).
      However, how these small NPs exert cytotoxicity in the living organisms has
      always been under heated debate. In this study, the uptake and toxicity effects
      of strongly red-emitting fluorescent silver nanoclusters (r-Ag NCs) exposed to
      the green algae Scenedesmus obliquus was investigated. Upon exposure to pure r-Ag
      NCs and r-Ag NCs containing l-cysteine, the algae growth inhibition test showed
      that Ag(+) ions released from r-Ag NCs played an important role in the toxicity
      of r-Ag NCs along with the toxicity of intact r-Ag NCs. Furthermore, no signals
      of intracellular reactive oxygen species (ROS) were observed indicating that r-Ag
      NCs or released Ag(+) ions - mediated growth inhibition of algae cells was
      independent of ROS production. Transmission electron microscopy (TEM) and laser
      scanning confocal microscopy (LSCM) were employed to study cellular uptake and
      cytotoxicity. Furthermore, analysis of differential expressed gene demonstrated
      that r-Ag NCs as well as the released Ag(+) ions can simultaneously exist inside
      the algae cells, and inhibit the transcriptomic process of genes by their "joint
      toxicity" mechanism. Taken together, our study provides a new insight into the
      molecular mechanisms of r-Ag NCs and Ag(+) ions exposure to the aquatic organism
      and can be applied to early diagnosis of ecologic risk mediated by others metal
      based NPs.

PMID- 27023121
TI  - Non-polar organic compounds in marine aerosols over the northern South China Sea:
      Influence of continental outflow.
AB  - Filter samples of total suspended particle (TSP) collected during a cruise
      campaign over the northern South China Sea (SCS) from September to October 2013
      were analyzed for non-polar organic compounds (NPOCs) as well as organic carbon
      (OC), elemental carbon (EC) and water-soluble ions. A total of 115 NPOCs species
      in groups of n-alkanes, polycyclic aromatic hydrocarbons (PAHs), iso-/antiso
      alkanes, hopanes, steranes, methylalkanes, branched alkanes, cycloalkanes,
      alkenes and phthalates were detected. The characteristics of NPOCs in marine TSP
      samples were investigated to understand the sources from the Asian continent and
      other regions. The concentrations of total NPOCs ranged from 19.8 to 288.2
      ng/m(3) with an average of 87.9 ng/m(3), which accounted for 0.8-1.7% (average
      1.0%) of organic matter (OM). n-Alkanes was the predominant group, accounting for
      43.1-79.5%, followed by PAHs (5.5-44.4%) and hopanes (1.6-11.4%). We found that
      primary combustion (biomass burning/fossil fuel combustion) was the dominant
      source for the majority of NPOCs (89.1%). Biomass burning in
      southern/southeastern China via long-range transport was proposed to be a major
      contributor of NPOCs in marine aerosols over the northern SCS, suggested by the
      significant correlations between nss-K(+) and NPOCs groups as well as the
      analysis of air mass back-trajectory and fire spots. For the samples with strong
      continental influence, the strong enhancement in concentrations of n-alkanes,
      PAHs, hopanes and steranes were attributed to fossil fuel (coal/petroleum)
      combustion. In addition, terrestrial plants waxes were another contributor to
      NPOCs.

PMID- 27023122
TI  - Preterm Premature Rupture of Membranes: A Constant Challenge in Perinatal
      Medicine?

PMID- 27023123
TI  - [Motor Skills of Extremely Obese Children and Adolescents Based on the
      Multicentre Longitudinal Obesity Database (APV)].
AB  - BACKGROUND: Obese children and adolescents often exhibit progressively declining
      motor skills. To support young obese patients adequately, it is necessary to
      assess their individual physical and motor abilities, taking the degree of
      obesity into account. PATIENTS: A total of 5 924 children and adolescents (mean
      age: 12.7+/-2.5 years, range 6.0-18.0 years, 3 195 girls) were examined in a
      standardised multicentre evaluation survey (APV). Fitness parameters were
      correlated with age- and gender-specific BMI-SDS (Standard Deviation Score)
      Methods: Anthropometric data were collected and patients performed the modified
      Munich fitness test (mMFT: maximal power, coordination, trunk flexibility) and a
      6-min walk-test (aerobic endurance capacity). RESULTS: 33% of patients were
      extremely obese (BMI>99.5th percentile). Mean BMI-SDS was + 2.32+/-0.53 (?
      Delta=+ 0.06; p<0.001). The data indicated significant negative correlations
      between BMI-SDS and selected components of motor performance, especially maximal
      power (r=- 0,134), and particularly aerobic endurance capacity (r=- 0,214; all
      p<0.001). Motor performance was significantly below average (n=27 473, 6-18
      years), especially among extremely obese patients. Performance in all motor tasks
      was lower in girls compared to boys, except for trunk flexibility (p<0.001).
      CONCLUSION: Correlations were found between BMI-SDS and motor performance.
      Extremely obese patients and obese girls showed the most pronounced motor
      deficits. These results emphasize the importance of standardized evaluation of
      individual motor performance in children and adolescents with obesity.

PMID- 27023124
TI  - [Minimal-invasive Cholecystocolostomy as Surgical Bridging Procedure in Patients
      with Progressive Familial Intrahepatic Cholestasis (PFIC)].

PMID- 27023125
TI  - An Unusual Case of Eczema.

PMID- 27023126
TI  - [Large Cardiac Fibroma in a 9-year-old Boy - Successful Surgical Resection in
      High Grade Ventricular Arrhythmias].

PMID- 27023127
TI  - Intracerebroventricular Injection of Amyloid-beta Peptides in Normal Mice to
      Acutely Induce Alzheimer-like Cognitive Deficits.
AB  - Amyloid-beta (Abeta) is a major pathological mediator of both familial and
      sporadic Alzheimer's disease (AD). In the brains of AD patients, progressive
      accumulation of Abeta oligomers and plaques is observed. Such Abeta abnormalities
      are believed to block long-term potentiation, impair synaptic function, and
      induce cognitive deficits. Clinical and experimental evidences have revealed that
      the acute increase of Abeta levels in the brain allows development of Alzheimer
      like phenotypes. Hence, a detailed protocol describing how to acutely generate an
      AD mouse model via the intracerebroventricular (ICV) injection of Abeta is
      necessary in many cases. In this protocol, the steps of the experiment with an
      Abeta-injected mouse are included, from the preparation of peptides to the
      testing of behavioral abnormalities. The process of preparing the tools and
      animal subjects before the injection, of injecting the Abeta into the mouse brain
      via ICV injection, and of assessing the degree of cognitive impairment are easily
      explained throughout the protocol, with an emphasis on tips for effective ICV
      injection of Abeta. By mimicking certain aspects of AD with a designated
      injection of Abeta, researchers can bypass the aging process and focus on the
      downstream pathology of Abeta abnormalities. 

PMID- 27023128
TI  - Genetics and Molecular Mapping of Black Rot Resistance Locus Xca1bc on Chromosome
      B-7 in Ethiopian Mustard (Brassica carinata A. Braun).
AB  - Black rot caused by Xanthomonas campestris pv. campestris (Pam.) Dowson is the
      most destructive disease of cauliflower causing huge loss to the farmers
      throughout the world. Since there are limited sources of resistance to black rot
      in B. oleracea (C genome Brassica), exploration of A and B genomes of Brassica
      was planned as these were thought to be potential reservoirs of black rot
      resistance gene(s). In our search for new gene(s) for black rot resistance, F2
      mapping population was developed in Brassica carinata (BBCC) by crossing NPC-17,
      a susceptible genotype with NPC-9, a resistant genotype. Out of 364 Intron length
      polymorphic markers and microsatellite primers used in this study, 41
      distinguished the parental lines. However, resistant and susceptible bulks could
      be distinguished by three markers At1g70610, SSR Na14-G02 and At1g71865 which
      were used for genotyping of F2 mapping population. These markers were placed
      along the resistance gene, according to order, covering a distance of 36.30 cM.
      Intron length polymorphic markers At1g70610 and At1g71865 were found to be linked
      to black rot resistance locus (Xca1bc) at 6.2 and 12.8 cM distance, respectively.
      This is the first report of identification of markers linked to Xca1bc locus in
      Brassica carinata on B-7 linkage group. Intron length polymorphic markers
      provided a novel and attractive option for marker assisted selection due to high
      cross transferability and cost effectiveness for marker assisted alien gene
      introgression into cauliflower. 

PMID- 27023129
TI  - Stability-indicating HPLC method development and structural elucidation of novel
      degradation products in posaconazole injection by LC-TOF/MS, LC-MS/MS and NMR.
AB  - Stress testing was carried out under acidic, alkaline, oxidative, thermal and
      photolytic conditions to evaluate the intrinsic stability of posaconazole
      injection. A total of four degradation products were detected and the drug was
      found to be susceptible to oxidative and thermal degradations. Three unknown
      degradants formed under oxidative stress condition were isolated by preparative
      HPLC and unambiguously elucidated by LC-TOF/MS, LC-MS/MS, (1)H NMR, (13)C NMR and
      2D NMR techniques. Based on the spectrometric and spectroscopic information,
      these novel degradation products were unequivocally assigned as the N-oxides of
      posaconazole. Probable mechanisms for the formation of the degradants were
      proposed. A new and selective HPLC method was developed and validated to
      separate, detect and quantify all the degradants in posaconazole injection. 

PMID- 27023130
TI  - Microwave-assisted ionic liquid homogeneous liquid-liquid microextraction coupled
      with high performance liquid chromatography for the determination of
      anthraquinones in Rheum palmatum L.
AB  - The microwave-assisted ionic liquid homogeneous liquid-liquid microextraction (MA
      IL-HLLME) coupled with high performance liquid chromatography with diode array
      detection (HPLC-DAD) was developed for the determination of anthraquinones,
      including aloe-emodin, emodin, chrysophanol and physcion in root of Rheum
      palmatum L. Several experimental parameters influencing the extraction
      efficiency, including amount of sample, type and volume of ionic liquid, volume
      and pH value of extraction medium, microwave power and extraction time,
      concentration of NH4PF6 as well as centrifugal condition were optimized. When
      140MUL of ionic liquid ([C8MIM][BF4]) was used as an extraction solvent, target
      analytes can be extracted from sample matrix in one minute with the help of
      microwave irradiation. The MA-IL-HLLME is simple and quick. The calibration
      curves exhibited good linear relationship (r>0.9984). The limits of detection and
      quantification were in the range of 0.015-0.026 and 0.051-0.088MUgmL(-1),
      respectively. The spiked recovery for each analyte was in the range of 81.13
      93.07% with relative standard deviations lower than 6.89%. The present method is
      free of volatile organic solvents, and represents lower expenditures of sample,
      extraction time and solvent, compared with ultrasonic and heat reflux extraction.
      The results indicated that the present method can be successfully applied to the
      determination of anthraquinones in medicinal plant. 

PMID- 27023131
TI  - Formation of copper(I) from trace levels of copper(II) as an artifactual impurity
      in the HPLC analysis of olanzapine.
AB  - An analytical artifact peak appearing to be an impurity was observed
      intermittently among several laboratories performing HPLC analyses of olanzapine
      drug substance and formulation samples. The artifact peak was identified as Cu(I)
      that was formed from the reaction of trace amounts of Cu(II) with olanzapine in
      the sample solution. Unlike Cu(II), Cu(I) was retained under the ion-pairing HPLC
      conditions used for analysis. A reaction mechanism was postulated whereby Cu(II)
      present in the sample solution oxidizes olanzapine to a radical-cation, resulting
      in formation of Cu(I) and three oxidation products of olanzapine including a
      previously unknown oxidation product that was identified as hydroxy-olanzapine.
      Acetonitrile in the sample solution was necessary for the reaction to occur. As
      little as 100 ppb Cu(II) in the sample solution produced a Cu(I) peak, that by
      peak area, corresponded to about 0.1% relative to the olanzapine peak. The
      hydroxy-olanzapine oxidation product was also detectable, but the relative peak
      area was much smaller. To prevent formation of the Cu(I) artifact peak, EDTA was
      added to the sample solvent to complex any trace Cu(II) that might be present.
      The addition of EDTA was shown to prevent Cu(I) formation when Cu(II) was present
      at levels of 4ppm in the sample solution. 

PMID- 27023133
TI  - Our PPT Community.

PMID- 27023132
TI  - Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small
      Intestine.
AB  - Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1), an apical membrane
      cholesterol transporter of enterocytes, thereby reduces intestinal cholesterol
      absorption. This treatment also increases extrahepatic reverse cholesterol
      transport via an undefined mechanism. To explore this, we employed a trans
      intestinal cholesterol efflux (TICE) assay, which directly detects circulation-to
      intestinal lumen 3H-cholesterol transit in a cannulated jejunal segment, and
      found an increase of TICE by 45%. To examine whether such increase in efflux
      occurs at the intestinal brush border membrane(BBM)-level, we performed luminal
      perfusion assays, similar to TICE but the jejunal wall was labelled with orally
      given 3H-cholesterol, and determined elevated BBM-to-lumen cholesterol efflux by
      3.5-fold with ezetimibe. Such increased efflux probably promotes circulation-to
      lumen cholesterol transit eventually; thus increases TICE. Next, we wondered how
      inhibition of NPC1L1, an influx transporter, resulted in increased efflux. When
      we traced orally-given 3H-cholesterol in mice, we found that lumen-to-BBM 3H
      cholesterol transit was rapid and less sensitive to ezetimibe treatment.
      Comparison of the efflux and fractional cholesterol absorption revealed an
      inverse correlation, indicating the efflux as an opposite-regulatory factor for
      cholesterol absorption efficiency and counteracting to the naturally-occurring
      rapid cholesterol influx to the BBM. These suggest that the ezetimibe-stimulated
      increased efflux is crucial in reducing cholesterol absorption. Ezetimibe-induced
      increase in cholesterol efflux was approximately 2.5-fold greater in mice having
      endogenous ATP-binding cassette G5/G8 heterodimer, the major sterol efflux
      transporter of enterocytes, than the knockout counterparts, suggesting that the
      heterodimer confers additional rapid BBM-to-lumen cholesterol efflux in response
      to NPC1L1 inhibition. The observed framework for intestinal cholesterol fluxes
      may provide ways to modulate the flux to dispose of endogenous cholesterol
      efficiently for therapeutic purposes. 

PMID- 27023134
TI  - Commentary on "Modified Constraint-Induced Movement Therapy as a Home-Based
      Intervention for Children With Cerebral Palsy".

PMID- 27023135
TI  - Commentary on "Benefits and Enjoyment of a Swimming Intervention for Youth With
      Cerebral Palsy: An RCT Study".

PMID- 27023136
TI  - Commentary on "Vestibular Assessments in Children With Global Developmental
      Delay: An Exploratory Study".

PMID- 27023137
TI  - Commentary on "The Effect of Ankle-Foot Orthoses on Community-Based Walking in
      Cerebral Palsy: A Clinical Pilot Study".

PMID- 27023138
TI  - Commentary on "Distal Vibration Perception Threshold in Children Who Toe Walk".

PMID- 27023139
TI  - Commentary on "Six-Minute Walk Test in Children With Spastic Cerebral Palsy and
      Children Developing Typically".

PMID- 27023140
TI  - Commentary on "Genu Valgum and Flat Feet in Children With Healthy and Excessive
      Body Weight".

PMID- 27023141
TI  - Commentary on "Preventing Weight Gain in Children Who Are School Age and African
      American".

PMID- 27023142
TI  - Commentary on "Inter- and Intrarater Reliability of the Infant Motor Profile in 3
      to 18-Month-Old Infants".

PMID- 27023143
TI  - Commentary on "Enabling 2-Wheeled Cycling for Youth With Down Syndrome".

PMID- 27023144
TI  - Commentary on "Analysis of PEDI Normative Data Between Spain and the United
      States".

PMID- 27023145
TI  - Commentary on "Timed Up and Go: Reference Data for Children Who Are School Age".

PMID- 27023146
TI  - Colorectal Cancer Genetic Heterogeneity Delineated by Multi-Region Sequencing.
AB  - Intratumor heterogeneity (ITH) leads to an underestimation of the mutational
      landscape portrayed by a single needle biopsy and consequently affects treatment
      precision. The extent of colorectal cancer (CRC) genetic ITH is not well
      understood in Chinese patients. Thus, we conducted deep sequencing by using the
      OncoGxOneTM Plus panel, targeting 333 cancer-specific genes in multi-region
      biopsies of primary and liver metastatic tumors from three Chinese CRC patients.
      We determined that the extent of ITH varied among the three cases. On average,
      65% of all the mutations detected were common within individual tumors. KMT2C
      aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent
      phylogenetic analysis showed that the tumors evolved in a branched manner.
      Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X),
      SETD2 (I1608V), SMAD4 (G382T), and AR splicing site mutations may be specific to
      liver metastatic cancer. These mutations might contribute to the initiation and
      progression of distant metastasis. Collectively, our analysis identified a
      substantial level of genetic ITH in CRC, which should be considered for
      personalized therapeutic strategies. 

PMID- 27023147
TI  - Preparation and Testing of Impedance-based Fluidic Biochips with RTgill-W1 Cells
      for Rapid Evaluation of Drinking Water Samples for Toxicity.
AB  - This manuscript describes how to prepare fluidic biochips with Rainbow trout gill
      epithelial (RTgill-W1) cells for use in a field portable water toxicity sensor. A
      monolayer of RTgill-W1 cells forms on the sensing electrodes enclosed within the
      biochips. The biochips are then used for testing in a field portable electric
      cell-substrate impedance sensing (ECIS) device designed for rapid toxicity
      testing of drinking water. The manuscript further describes how to run a toxicity
      test using the prepared biochips. A control water sample and the test water
      sample are mixed with pre-measured powdered media and injected into separate
      channels of the biochip. Impedance readings from the sensing electrodes in each
      of the biochip channels are measured and compared by an automated statistical
      software program. The screen on the ECIS instrument will indicate either
      "Contamination Detected" or "No Contamination Detected" within an hour of sample
      injection. Advantages are ease of use and rapid response to a broad spectrum of
      inorganic and organic chemicals at concentrations that are relevant to human
      health concerns, as well as the long-term stability of stored biochips in a ready
      state for testing. Limitations are the requirement for cold storage of the
      biochips and limited sensitivity to cholinesterase-inhibiting pesticides.
      Applications for this toxicity detector are for rapid field-portable testing of
      drinking water supplies by Army Preventative Medicine personnel or for use at
      municipal water treatment facilities. 

PMID- 27023148
TI  - Double-domed horizontal fissure.

PMID- 27023150
TI  - RSO Interview with Elizabeth Oseid.

PMID- 27023149
TI  - Perfusion parameters as potential imaging biomarkers for the early prediction of
      radiotherapy response in a rat tumor model.
AB  - PURPOSE: We aimed to compare various tumor-related radiologic morphometric
      changes and computed tomography (CT) perfusion parameters before and after
      treatment, and to determine the optimal imaging assessment technique for the
      prediction of early response in a rat tumor model treated with radiotherapy.
      METHODS: Among paired tumors of FN13762 murine breast cancer cells implanted
      bilaterally in the necks of eight Fischer rats, tumors on the right side were
      treated with a single 20 Gy dose of radiotherapy. Perfusion CT studies were
      performed on day 0 before radiotherapy, and on days 1 and 5 after radiotherapy.
      Variables based on the size, including the longest diameter, tumor area, and
      volume, were measured. Quantitative perfusion analysis was performed for the
      whole tumor volume and permeabilities and blood volumes (BVs) were obtained. The
      area under the curve (AUC) difference in the histograms of perfusion parameters
      and texture analyses of uniformity and entropy were quantified. Apoptotic cell
      density was measured on pathology specimens immediately after perfusion imaging
      on day 5. RESULTS: On day 1 after radiotherapy, differences in size between the
      irradiated and nonirradiated tumors were not significant. In terms of percent
      changes in the uniformity of permeabilities between tumors before irradiation and
      on day 1 after radiotherapy, the changes were significantly higher in the
      irradiated tumors than in the nonirradiated tumors (0.085 [-0.417, 0.331] vs. 
      0.131 [-0.536, 0.261], respectively; P = 0.042). The differences in AUCs of the
      histogram of voxel-by-voxel vascular permeability and BV in tumors between day 0
      and day 1 were significantly higher in treated tumors compared with the control
      group (permeability, 21.4 [-2.2, 37.5] vs. 9.5 [-8.9, 33.8], respectively, P =
      0.030; BV, 52.9 [-6186.0, 419.2] vs. 11.9 [-198.3, 346.7], respectively, P =
      0.049). Apoptotic cell density showed a significantly positive correlation with
      the AUC difference of BV, the percent change of uniformity in permeability and BV
      (r=0.202, r=0.644, and r=0.706, respectively). CONCLUSION: By enabling earlier
      tumor response prediction than morphometric evaluation, the histogram analysis of
      CT perfusion parameters appears to have a potential in providing prognostic
      predictive information in an irradiated rat model.

PMID- 27023151
TI  - Radiation Safety among Workers in Health Services.
AB  - The purpose of this study was to survey health service workers regarding their
      radiation safety knowledge and practice. Participants were health service workers
      (n = 721) who received an anonymous online survey by email to test their
      radiation safety knowledge. A knowledge test of 15 questions was completed by 412
      respondents. The overall average percent correct was 77.9%. Health
      physicists/medical physicists had the highest average percent score (93.5%),
      while physician assistants scored the lowest (60.0%). Of all the respondents,
      only 64.0% reported they participated in periodic radiation safety training at
      their place of employment. The most common topic selected where participants
      wanted additional training was in biological effects of radiation (41.0%). In
      conclusion, radiation safety training and education needs to be developed and
      planned effectively. Areas or specialties with poor radiation safety knowledge
      need to be addressed with corresponding safety measures. 

PMID- 27023152
TI  - In-Place Filter Tester Instrument for Nuclear Material Containers.
AB  - A portable instrument was developed to determine filter clogging and container
      leakage of in-place nuclear material storage canisters. This paper describes the
      development of an in-place filter tester for determining the "as found" condition
      of unopened canisters. The U.S. Department of Energy uses several thousand
      canisters for nuclear material storage, and air filters in the canister lids
      allow gases to escape while maintaining an equilibrated pressure without release
      of radioactive contamination. Diagnosing the filter condition and canister
      integrity is important for ensuring worker and public safety. Customized canister
      interfaces were developed for suction clamping (during tests) to two of the
      canister types in use at Los Alamos National Laboratory. Experimental leakage
      scenarios included: O-rings fouled with dust, cracked O-rings, and loose canister
      lids. The prototype tester has a measurement range for air leakage rates from 8.2
      * 10 mL s up to 3.0 * 10 mL s. This is sufficient to measure a leak rate of 3.4 *
      10 mL s, which is the Los Alamos helium leak criterion for post-drop tested
      canisters. The In-Place-Filter-Tester cannot measure to the lower value of the
      helium leak criterion for pre-drop tested canisters (1.0 * 10 mL s). However,
      helium leak testing requires canister disassembly, while the new in-place filter
      tester is able to assess the assembled condition of as-found and in-situ
      canisters. 

PMID- 27023153
TI  - Using a Spreadsheet to Compute the Maximum Wind Sector 99.5th Percentile X/Q
      Value in Accordance with DOE-STD-3009-2014.
AB  - The U.S. Department of Energy Standard 3009-2014 requires one of two methods to
      determine the simple Gaussian relative concentration (X/Q) of pollutant at plume
      centerline downwind to a receptor for a 2-h exposure duration from a ground-level
      release (i.e., less than 10 m height) which are (1) the 99.5th percentile X/Q for
      the directionally-dependent method and (2) the 95th percentile X/Q for the
      directionally-independent method. This paper describes how to determine the
      simple Gaussian 99.5th percentile X/Q for the directionally-dependent method
      using an electronic spreadsheet. Refer to a previous paper to determine the
      simple Gaussian 95th percentile X/Q for the directionally-independent method
      using an electronic spreadsheet (Vickers 2015). The method described herein is
      simple, quick, accurate, and transparent because all of the data, calculations,
      and results are visible for validation and verification. 

PMID- 27023154
TI  - Radiation Monitoring Results from the First Year of Operation of a Unique
      Ambulance-based Computed Tomography Unit for the Improved Diagnosis and Treatment
      of Stroke Patients.
AB  - When a blood clot blocks the blood supply to the brain or when a blood vessel
      bursts, resulting in brain cell death, the medical condition is referred to as a
      "stroke." Stroke is a main cause of death worldwide and is a common cause of
      disability. A common form of stroke, called ischemic stroke, is when blood flow
      to the brain is decreased. Clinical research has revealed that treatment within
      the very first hours of symptom onset is key for ischemic stroke with
      recanalization of occluded arteries by thrombolysis with alteplase. Computed
      tomography (CT) is one of the diagnostic tools used to determine if this
      treatment path is appropriate. To determine if health outcomes of possible stroke
      patients can be improved by decreasing the time from symptom presentation to
      treatment, the first mobile stroke ambulance unit in the United States was
      deployed by The University of Texas Health Science Center at Houston (UTHealth)
      in 2014, equipped with a computed tomography imaging system. The mobile stroke
      unit shortens the time to treatment for stroke patients by allowing pre-hospital
      treatment. Having completed its first year of operation, radiation-monitoring
      data describing the doses delivered to various entities have been characterized.
      The CT operator's cumulative deep dose equivalent for 1 y of operation was 1.14
      mSv resulting from the care of 106 patients. Area monitors were deployed and
      measurements performed demonstrating that general public doses did not exceed
      0.02 mSv h-1 or 1.0 mSv year.

PMID- 27023155
TI  - Evaluation of IAEA Clearance Concept for Low-level Radioactive Waste from a
      Radioisotope Research Institute.
AB  - The clearance of solid low-level radioactive laboratory waste (LLRW) after decay
      in-storage (DIS) obtained from a research institute and thoroughly separated
      using the separation and classification protocols presented in this study was
      evaluated. METHOD: The radioisotope (RI) content of incinerated LLRW from the
      specified RI research group (group A); the RI content of LLRW obtained in fiscal
      year 2000, which contained radionuclides with half-lives of less than 164 d
      (LLRW2); and the RI content of the LLRW reported in group A's disposal records
      were compared. The LLRW2 and LLRW of group A were incinerated after 2 y of decay
      in-storage and immediately after storage, respectively. RESULTS: The highest
      ratio of the RI of incinerated LLRW to the value in the disposal records was 2.52
      for 51Cr. The radioactivities of radionuclides in both the LLRW2 and LLRW for
      35S, 45Ca, 51Cr, 125I, 32P, 33P, and 99mTc and the incinerated ash after 1 y
      later of decay-in-storage were below the clearance level defined by the RS-G-1.7
      of the International Basic Safety Standard without contamination by 3H and 14C.
      These remains contained very small amounts of some long-half-life radionuclides
      of natural origin after 7 y of decay-in-storage. CONCLUSION: This LLRW separation
      protocol was effective for the separation of 3H and 14C. LLRW2 after 2 years of
      DIS and its incinerated ash after one year later of DIS were below the clearance
      level for radioactivity and radioactivity concentration.

PMID- 27023156
TI  - (14)C levels in the vicinity of the Fukushima Dai-ichi Nuclear Power Plant prior
      to the 2011 accident.
AB  - A 50-year-old Japanese cedar (Cryptomeria japonica) from Okuma, ~1 km southwest
      of the Fukushima Dai-ichi Nuclear Power Plant, was cored and each annual ring was
      analysed for (14)C. The (14)C specific activity values varied from 330.4 Bq kg(
      1) C in the tree ring formed in 1971 to 231.2 Bq kg(-1) C in the 2014 ring.
      During the periods 1971-1976 and 2011-2014, the (14)C specific activities are
      indistinguishable from the ambient background values. However, compared with the
      ambient atmospheric levels, the (14)C specific activities between 1977 and 2010
      are significantly elevated, clearly indicating (14)C discharges from the reactors
      during their normal operations. In addition, the specific activities are
      positively correlated with the annual electricity generation values. The excess
      (14)C specific activities were <36 Bq kg(-1) C, corresponding to an additional
      annual effective dose of <2 MUSv via the food ingestion pathway in the study
      location. The primary wind direction is east-southeast/southeast with a frequency
      of ~30%, in comparison to ~20% frequency for the direction of the site under
      study (north-northeast/northeast). This would tend to indicate a similar
      magnitude of additional effective dose and consequently no significant
      radiological impact of atmospheric (14)C discharges from the FDNPP during the
      entire period of normal operations. Additionally, no (14)C pulse in activity can
      be observed in the year 2011 ring. This might be caused by a limited (14)C
      release from the damaged reactors during the accident or that the prevailing wind
      during the short period of release (11th-25th March 2011) was not in the
      direction of Okuma. 

PMID- 27023157
TI  - Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in
      red blood cells.
AB  - Though blood bank processing traditionally employs centrifugation, new separation
      techniques may be appealing for large scale processes. Split-flow fractionation
      (SPLITT) is a family of techniques that separates in absence of labelling and
      uses very low flow rates and force fields, and is therefore expected to minimize
      cell damage. However, the hydrodynamic stress and possible consequent damaging
      effects of SPLITT fractionation have not been yet examined. The aim of this study
      was to investigate the hydrodynamic damage of SPLITT fractionation to human red
      blood cells, and to compare these effects with those induced by centrifugation.
      Peripheral whole blood samples were collected from healthy volunteers. Samples
      were diluted in a buffered saline solution, and were exposed to SPLITT
      fractionation (flow rates 1-10 ml/min) or centrifugation (100-1500 g) for 10 min.
      Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane
      potential were measured. Under the operating conditions employed, both SPLITT and
      centrifugation maintained cell viability above 98%, but resulted in significant
      sublethal damage, including echinocyte formation, decreased cell diameter,
      decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was
      inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed
      significant correlation with lethal and sublethal damage. Our data do not support
      the assumption that SPLITT fractionation induces very low shear stress and is
      innocuous to cell function. Some changes in SPLITT channel design are suggested
      to minimize cell damage. Measurement of membrane potential and cell diameter
      could provide a new, reliable and convenient basis for evaluation of hydrodynamic
      effects on different cell models, allowing identification of optimal operating
      conditions on different scales.

PMID- 27023158
TI  - Simultaneous determination of shanzhiside methyl ester, 8-O-acetylshan- zhiside
      methyl ester and luteolin-7-O-beta-D-glucopyranoside in rat plasma by ultra
      performance liquid chromatography-tandem mass spectrometry and its application to
      a pharmacokinetic study after oral administration of Lamiophlomis rotata Pill.
AB  - A rapid, sensitive and specific ultra performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) method for the quantification of shanzhiside
      methyl ester, 8-O-acetylshanzhiside methyl ester and luteolin-7-O-beta-D
      glucopyranoside of Lamiophlomis rotata Pill in rat plasma was developed and
      validated. After liquid-liquid extraction with n-butyl alcohol/ethyl acetate
      (70:30, v/v), analytes and paeoniflorin (internal standard, IS) were separated on
      an Acquity BEH UPLC C18 column (100 * 2.1 mm, 1.7 MUm) with gradient elution at a
      flow rate of 0.2 mL/min. All calibration curves had good linearity (r>0.9929)
      over the concentration ranges of 1-1000 ng/mL for shanzhiside methyl ester and 8
      O-acetylshanzhiside methyl ester, 0.3-150 ng/mL for luteolin-7-O-beta-D
      glucopyranoside. The intra- and inter-day precisions were all within 11.1% and
      the accuracy (relative error, RE%) all ranged from -13.6% to 5.3%. The method
      also guaranteed an acceptable selectivity, recovery and stability, which was
      successfully applied to a pharmacokinetic study of the three analytes in rats
      after oral administration of Lamiophlomis rotata Pill.

PMID- 27023159
TI  - A fully validated LC-MS/MS method for simultaneous determination of nicotine and
      its metabolite cotinine in human serum and its application to a pharmacokinetic
      study after using nicotine transdermal delivery systems with standard heat
      application in adult smokers.
AB  - A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method was developed and validated for simultaneous determination of nicotine and
      its main metabolite cotinine in human serum samples. Liquid-liquid extraction
      using ethyl acetate was employed for serum sample extractions. Chromatographic
      separation was achieved on Phenomenex Luna((r)) HILIC column (150 mm x 3.0mm, 5
      MUm). Isocratic elution was performed using acetonitrile:100mM ammonium formate
      buffer (pH=3.2) (90:10, v/v) as the mobile phase, at a flow rate of 0.4 mL/min.
      Tandem mass spectrometric detection was employed at positive electrospray
      ionization in MRM mode for the determination of both nicotine and cotinine and
      their stable isotope labeled internal standards. Analysis was carried out in 8
      min over a concentration range of 0.26-52.5 ng/mL and 7.0-1500 ng/mL for nicotine
      and cotinine, respectively. The assay was validated according to FDA guidelines
      for bioanalytical method validation and satisfactory results were obtained; the
      accuracy ranged between 93.39% and 105.73% for nicotine and between 93.04% and
      107.26% for cotinine. No significant matrix effect was observed. Stability assays
      indicated both nicotine and cotinine were stable during sample storage,
      preparation and analytical procedures. The method was successfully applied to
      biological samples obtained from a pharmacokinetic study conducted in adult
      smokers to investigate heat effect on nicotine and cotinine serum levels after
      nicotine transdermal delivery system (TDS) application.

PMID- 27023160
TI  - Spectroscopic studies of the ferroelectric and magnetic phase transitions in
      multiferroic Sr1-xBaxMnO3.
AB  - Dielectric response of perovskite Sr1-xBaxMnO3 (x = 0.43 and 0.45) ceramics was
      investigated using microwave, THz and infrared spectroscopic techniques in order
      to study the ferroelectric and antiferromagnetic phase transitions with critical
      temperatures TC ~ 350 K and TN ~ 200 K, respectively. The two lowest-frequency
      polar phonons are overdamped above TN and they exhibit pronounced softening on
      heating towards TC. Nevertheless, permittivity epsilon' in the THz range shows
      only a small anomaly at TC because the phonon contribution to epsilon' is rather
      small. The phonons are coupled with a central mode which provides the main
      contribution to the dielectric anomaly at TC. Thus, the ferroelectric phase
      transition has characteristics of a crossover from displacive to order-disorder
      type. At the same time, the intrinsic THz central peak is partially screened by
      conductivity and related Maxwell-Wagner relaxation, which dominates the microwave
      and lower-frequency spectra. Below TN, the ferroelectric distortion markedly
      decreases, which has an influence on the frequencies of both the central and soft
      modes. Therefore, epsilon' in the THz range increases at TN on cooling. In spite
      of the strong spin-phonon coupling near TN, surprisingly no magnetodielectric
      effect was observed in the THz spectra upon applying magnetic field of up to 7 T,
      which is in contradiction with the theoretically expected huge magnetoelectric
      coupling. We explain this fact as due to the insensitivity of TN to magnetic
      field.

PMID- 27023161
TI  - Direct acting antiviral therapy after liver transplantation.
AB  - PURPOSE OF REVIEW: Historically, postliver transplant patients with chronic
      hepatitis C have had worse outcomes than nonhepatitis C-related causes because of
      accelerated fibrosis posttransplantation and the lack of effective well tolerated
      therapies for hepatitis C, and posttransplant hepatitis C patients have been
      considered a special population. Since 2013, we have entered the era of all oral
      direct acting antiviral agents for hepatitis C with sustained response rates that
      are consistently above 90% in nontransplant patients. RECENT FINDINGS: The
      introduction of direct acting antiviral agents to posttransplant patients has
      demonstrated that sustained virologic response rates that are comparable with
      nontransplant patients can be achieved with excellent tolerability. The
      combinations of sofosbuvir/ribavirin, ledipasvir/sofosbuvir/ribavirin,
      daclatasvir/sofosbuvir/ribavirin, sofosbuvir/simeprevir +/- ribavirin, and
      paritaprevir/ombitasvir/dasabuvir/ribavirin have all achieved high sustained
      response rates posttransplants. The previously dreaded complication of fibrosing
      cholestatic hepatitis C can now be effectively treated. SUMMARY: In the era of
      all oral therapies, no patient who undergoes transplant for hepatitis C-related
      cirrhosis should have their graft fail because of recurrent hepatitis C. It is
      expected that long-term survival of those who undergo orthotopic liver transplant
      for HCV-related cirrhosis will be comparable to those without hepatitis C.

PMID- 27023162
TI  - Treatment of chronic hepatitis C in patients with cirrhosis.
AB  - PURPOSE OF REVIEW: This article reviews treatment options of the approved and
      soon-to-be approved direct-acting antivirals (DAA)-based therapies in individuals
      with hepatitis C virus (HCV) cirrhosis. RECENT FINDINGS: DAA-based therapies have
      been shown to be well tolerated and effective in achieving viral cure in
      individuals with compensated and decompensated cirrhosis. Preliminary studies
      suggest that viral eradication arrests fibrosis progression and could lead to
      fibrosis regression. Long-term benefits of successful HCV treatment in this
      population translate into less frequent hepatic decompensation and hepatocellular
      carcinoma development, improvements in liver disease severity, reduction of liver
      related mortality, and potential obviation of the need for transplantation. The
      optimization of viral eradication rates requires longer duration therapy and/or
      more complex combinations of drugs, including ribavirin. Treatment decisions are
      guided by HCV genotype, renal function, drug-drug interactions, and the severity
      of cirrhosis. Safety concerns are paramount in individuals with advanced liver
      disease and continued vigilance for hepatotoxicity and other complications is
      warranted, especially in those with decompensated cirrhosis. SUMMARY: The
      availability of high potency DAA-based therapies with excellent safety profiles
      has transformed the HCV-infected cirrhotic population into a group that is no
      longer 'difficult-to-treat'. Understanding the pretreatment factors that predict
      clinical benefits vs. harm remains key in treating this population.

PMID- 27023163
TI  - Acute on chronic liver failure: definitions, treatments and outcomes.
AB  - PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) causes significant
      morbidity and mortality in patients with cirrhosis and/or chronic liver disease
      (CLD). The purpose of this review is to highlight recent studies that have better
      defined ACLF, and to highlight current outcomes and treatment strategies. RECENT
      FINDINGS: Currently, there are no clear definitions for ACLF; however, ACLF
      requires a precipitating event that occurs in the setting of cirrhosis and/or
      CLD, and progresses rapidly to multiorgan failure with high mortality. Most
      precipitants of ACLF are due to infections, leading to inflammatory cascades,
      hence early treatment with antibiotics in these cases might show benefit.
      Prognosis in ACLF typically depends on the number of extrahepatic organs
      affected. Potential biomarkers in ACLF may result in early detection and risk
      stratification; however, further research is needed. ACLF portends a poor
      prognosis; however, rescue therapy with liver transplantation has been considered
      in selected cases. SUMMARY: ACLF is a common and devastating complication of
      cirrhosis or CLD. ACLF usually requires a precipitating event and rapid
      progression to multiorgan failure with high mortality. Although signs and
      symptoms might overlap in patients with ACLF and those with decompensated
      cirrhosis, the two entities should be distinguished separately (although it is
      challenging to differentiate these in certain cases). Furthermore, diagnosing
      each entity should be based on a variety of clinical indicators, laboratory data
      and precipitating factors, in order to determine the best possible targeted
      treatment strategies. Refinement in the clinical definitions for ACLF may lead to
      better management and possibly better outcomes if recognized early.

PMID- 27023164
TI  - Transoral incisionless fundoplication: current status.
AB  - PURPOSE OF REVIEW: Transoral incisionless fundoplication (TIF) performed with the
      EsophyX device (Redmond, Washington, USA) is a totally endoscopic procedure with
      the objectives to mechanically repair a defective gastroesophageal valve and to
      reduce small hiatal hernias. The recent publication of randomized controlled
      trials and long-term follow-up data offers the opportunity to reevaluate this
      treatment modality and its role in the management of patients with chronic
      gastroesophageal reflux disease (GERD). RECENT FINDINGS: Randomized controlled
      trials have confirmed the ability of TIF to eliminate troublesome GERD symptoms,
      heal esophagitis, and improve distal esophageal acid exposure in appropriately
      selected patient populations. These studies establish TIF's superiority to
      conventional medical therapy, especially in clinical scenarios where proton-pump
      inhibitors fail to provide complete symptom relief across the spectrum of classic
      and atypical GERD manifestations, including regurgitation and laryngopharyngeal
      reflux. Long-term data indicate sustained positive outcomes and durability up to
      6 years after procedure. These results were achieved with a low rate of serious
      adverse events and usually without introducing troublesome dysphagia, gas bloat,
      or flatulence. SUMMARY: Based on the most recent data, TIF appears to be a
      valuable treatment alternative for the management of appropriately selected
      patients with moderate to severe chronic GERD symptoms.

PMID- 27023165
TI  - Biofilm Formation, Virulence Gene Profiles, and Antimicrobial Resistance of Nine
      Serogroups of Non-O157 Shiga Toxin-Producing Escherichia coli.
AB  - The objectives of this study were to characterize the phenotype and genotype of
      36 non-O157 Shiga toxin-producing Escherichia coli (STEC) strains isolated from
      humans, ovines, or bovines, including the top 6 (O26, O45, O103, O111, O121, and
      O145) and three other serogroups implicated in serious illness (O91, O113, and
      O128). Biofilms were formed by all strains with intermediate to strong biofilm
      producers (n = 24) more common at 22 degrees C than at 37 degrees C (p < 0.001)
      and 48 and 72 h (p < 0.001) than 24 h of incubation time. Biofilm-forming
      potential differed by serogroup and origin with O113 and human strains exhibiting
      the highest potential (p < 0.001). Biofilm-associated genes, csgA/csgD/crl/fimH
      (100%), flu (94%), rpoS (92%), ehaA(alpha) (89%), and cah (72%), were most
      prevalent, while mlrA (22%) and ehaA(beta) (14%) were least prevalent, although
      there was no clear compliment of genes associated with strains exhibiting the
      greatest biofilm-forming capacity. Among 12 virulence genes screened, iha and
      ehxA were present in 92% of the strains. The occurrence of stx1 in the top 6
      serogroups (8/12, 67%) did not differ (p = 0.8) from other serogroups (17/24,
      71%), but stx2 was less likely (confidence interval [CI] = 0.14-1.12; p = 0.04)
      to be in the former (9/24, 38%) than the latter (9/12, 75%). Excluding
      serogroups, O91 and O121, at least one strain per serogroup was resistant to
      between three and six antimicrobials. Streptomycin (31%), sulfisoxazole (31%),
      and tetracycline (25%) resistance was most common and was 35-50% less likely (p <
      0.05) in human than animal strains. All non-O157 STEC strains were able to form
      biofilms on an abiotic surface, with some exhibiting resistance to multiple
      antimicrobials. Potential as a reservoir of antimicrobial resistance genes may be
      another hazard of biofilms in food-processing plants. As a result, future
      strategies to control these pathogens may include measures to prevent biofilms.

PMID- 27023166
TI  - Synthesis of (+/-)-Bisavenanthramide B-6 by an Anionic Anhydride Mannich
      Reaction.
AB  - Bisavenanthramide B-6 (2) is a highly substituted gamma-lactam derived from oat
      leaves. Development of a new base-promoted anhydride Mannich reaction with N
      sulfonylated imines that forms the core structure of 2 in a single step is
      presented. Further elaboration allows for a facile one-pot double Buchwald N
      arylation to install the final rings onto the densely substituted gamma-lactam
      core. This route provides the natural product in a longest linear sequence of
      nine steps. 

PMID- 27023168
TI  - Mary Seacole Robinson Jane Mary Seacole 288pp Constable 9781841196770 1841196770.
AB  - At last, a biography of Mary Seacole. Written by Jane Robinson, a noted author on
      women travellers, the publication coincides with the bicentenary of Ms Seacole's
      birth. While making plentiful reference to Ms Seacole's 1857 autobiography,
      congratulations are due to Ms Robinson for unearthing new information about her
      subject. One example is Ms Seacole's putative father, a Scottish army officer
      called James Grant. It also seems to throw cold water on the allegation, made by
      Florence Nightingale to her sister Parthenope, that Ms Seacole had an
      illegitimate daughter by a Colonel Bunbury. In contrast, the biographer is
      clearly frustrated that her enquiries in Jamaica failed to uncover Ms Seacole's
      exact date of birth.

PMID- 27023169
TI  - The Good Appraisal Toolkit for Primary Care Chambers Ruth et al The Good
      Appraisal Toolkit for Primary Care 189pp Radcliffe Publishing 9781857756029
      1857756029.
AB  - The principles and frameworks demonstrated in this book could be used in many
      other healthcare settings. The text is divided neatly into nine chapters and
      addresses practical issues such as being an effective appraiser, developing and
      demonstrating competence, linking appraisal with career development, and
      evaluation of the appraisal process. The comprehensive approach to all aspects of
      appraisal makes this a must-have book for all health professionals and managers
      undertaking appraisals. It should also appeal to clinical governance leads and
      individuals being appraised. There are excellent tips on how to prepare for
      appraisals and how to link this with reflection, lifelong learning, career
      direction, and so on. The book is well referenced and contains an appendix with
      useful examples for the appraiser.

PMID- 27023167
TI  - Glaucoma-inducing Procedure in an In Vivo Rat Model and Whole-mount Retina
      Preparation.
AB  - Glaucoma is a disease of the central nervous system affecting retinal ganglion
      cells (RGCs). RGC axons making up the optic nerve carry visual input to the brain
      for visual perception. Damage to RGCs and their axons leads to vision loss and/or
      blindness. Although the specific cause of glaucoma is unknown, the primary risk
      factor for the disease is an elevated intraocular pressure. Glaucoma-inducing
      procedures in animal models are a valuable tool to researchers studying the
      mechanism of RGC death. Such information can lead to the development of effective
      neuroprotective treatments that could aid in the prevention of vision loss. The
      protocol in this paper describes a method of inducing glaucoma - like conditions
      in an in vivo rat model where 50 ul of 2 M hypertonic saline is injected into the
      episcleral venous plexus. Blanching of the vessels indicates successful
      injection. This procedure causes loss of RGCs to simulate glaucoma. One month
      following injection, animals are sacrificed and eyes are removed. Next, the
      cornea, lens, and vitreous are removed to make an eyecup. The retina is then
      peeled from the back of the eye and pinned onto sylgard dishes using cactus
      needles. At this point, neurons in the retina can be stained for analysis.
      Results from this lab show that approximately 25% of RGCs are lost within one
      month of the procedure when compared to internal controls. This procedure allows
      for quantitative analysis of retinal ganglion cell death in an in vivo rat
      glaucoma model. 

PMID- 27023170
TI  - Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations
      in immunological and neurodevelopmental pathways.
AB  - Studies of rare genetic variation have identified molecular pathways conferring
      risk for developmental neuropsychiatric disorders. To date, no published whole
      exome sequencing studies have been reported in obsessive-compulsive disorder
      (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and
      their unaffected parents to identify rare de novo (DN) single-nucleotide variants
      (SNVs). The primary aim of this pilot study was to determine whether DN variation
      contributes to OCD risk. To this aim, we evaluated whether there is an elevated
      rate of DN mutations in OCD, which would justify this approach toward gene
      discovery in larger studies of the disorder. Furthermore, to explore functional
      molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a
      protein-protein interaction (PPI) network was generated based on databases of
      direct molecular interactions. We applied Degree-Aware Disease Gene
      Prioritization (DADA) to rank the PPI network genes based on their relatedness to
      a set of OCD candidate genes from two OCD genome-wide association studies
      (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a
      pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was
      2.51 * 10(-8) per base per generation, significantly higher than a previous
      estimated rate in unaffected subjects using the same sequencing platform and
      analytic pipeline. Several genes harboring DN SNVs in OCD were highly
      interconnected in the PPI network and ranked high in the DADA analysis. Nearly
      all the DN SNVs in this study are in genes expressed in the human brain, and a
      pathway analysis revealed enrichment in immunological and central nervous system
      functioning and development. The results of this pilot study indicate that
      further investigation of DN variation in larger OCD cohorts is warranted to
      identify specific risk genes and to confirm our preliminary finding with regard
      to PPI network enrichment for particular biological pathways and functions. 

PMID- 27023173
TI  - A high-risk group of pregnant women with elevated levels of conflict-related
      trauma, intimate partner violence, symptoms of depression and other forms of
      mental distress in post-conflict Timor-Leste.

PMID- 27023171
TI  - The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord
      blood.
AB  - Compelling evidence suggests that maternal mental health in pregnancy can
      influence fetal development. The imprinted genes, insulin-like growth factor 2
      (IGF2) and H19, are involved in fetal growth and each is regulated by DNA
      methylation. This study aimed to determine the association between maternal
      mental well-being during pregnancy and differentially methylated regions (DMRs)
      of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn
      offspring. Maternal depression, anxiety and perceived stress were assessed at 28
      weeks of pregnancy in the Barwon Infant Study (n=576). DNA methylation was
      measured in purified cord blood mononuclear cells using the Sequenom MassArray
      Platform. Maternal anxiety was associated with a decrease in average ICR
      methylation (Delta=-2.23%; 95% CI=-3.68 to -0.77%), and across all six of the
      individual CpG units in anxious compared with non-anxious groups. Birth weight
      and sex modified the association between prenatal anxiety and infant methylation.
      When stratified into lower (?3530 g) and higher (>3530 g) birth weight groups
      using the median birth weight, there was a stronger association between anxiety
      and ICR methylation in the lower birth weight group (Delta=-3.89%; 95% CI=-6.06
      to -1.72%), with no association in the higher birth weight group. When stratified
      by infant sex, there was a stronger association in female infants (Delta=-3.70%;
      95% CI=-5.90 to -1.51%) and no association in males. All the linear regression
      models were adjusted for maternal age, smoking and folate intake. These findings
      show that maternal anxiety in pregnancy is associated with decreased IGF2/H19 ICR
      DNA methylation in progeny at birth, particularly in female, low birth weight
      neonates. ICR methylation may help link poor maternal mental health and adverse
      birth outcomes, but further investigation is needed.

PMID- 27023172
TI  - Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive
      behavior and memory deficits in mouse.
AB  - JMJD2B is a histone demethylase enzyme that regulates gene expression through
      demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be
      responsible for neurodevelopmental disorders, the function of JMJD2B in the
      central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B
      has a critical role in the development of the CNS. We observed JMJD2B expression,
      which was especially strong in the hippocampus, throughout the CNS from embryonic
      periods through adulthood. We generated neuron-specific JMJD2B-deficient mice
      using the cre-loxP system. We found an increase in total spine number, but a
      decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient
      mice exhibited hyperactive behavior, sustained hyperactivity in a novel
      environment, deficits in working memory and spontaneous epileptic-like seizures.
      Together these observations indicate that JMJD2B mutant mice display symptoms
      reminiscent of neurodevelopmental disorders. Our findings provide evidence for
      the involvement of histone demethylation in the formation of functional neural
      networks during development. 

PMID- 27023174
TI  - Exon-focused genome-wide association study of obsessive-compulsive disorder and
      shared polygenic risk with schizophrenia.
AB  - Common single-nucleotide polymorphisms (SNPs) account for a large proportion of
      the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and
      schizophrenia is commoner than expected based on their respective prevalences,
      complicating the clinical management of patients. This study addresses two main
      objectives: to identify particular genes associated with OCD by SNP-based and
      gene-based tests; and to test the existence of a polygenic risk shared with
      schizophrenia. The primary analysis was an exon-focused genome-wide association
      study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based
      on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was
      tested in our OCD data. A polygenic risk model based on our OCD data was tested
      on previous data of schizophrenia from our group. The most significant
      association at the gene-based test was found at DNM3 (P=7.9 * 10(-5)), a gene
      involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2
      data was strongly associated with disease status in our OCD sample, reaching its
      most significant value after removal of the major histocompatibility complex
      region (lowest P=2.3 * 10(-6), explaining 3.7% of the variance). The shared
      polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may
      be involved in risk to OCD. The shared polygenic risk between schizophrenia and
      OCD may be partially responsible for the frequent comorbidity of both disorders,
      explaining epidemiological data on cross-disorder risk. This common etiology may
      have clinical implications. 

PMID- 27023177
TI  - Modifiable risk factors for nursing home admission among individuals with high
      and low dementia risk.
AB  - BACKGROUND: Strategies to prevent or delay nursing home admission in individuals
      with cognitive impairment are urgently needed. We hypothesized that physical
      inactivity, not consuming alcohol (as opposed to moderate alcohol use), and
      having a history of smoking predict nursing home admission among individuals with
      normal cognitive function, but these behavioral factors would have attenuated
      associations with nursing home admission among individuals with impaired
      cognition. METHODS: We performed a prospective cohort study among 7631 Health and
      Retirement Study participants aged 65+ at baseline. Baseline dementia risk (high
      versus low, based on brief psychometric assessments and proxy reports) and
      modifiable risk factors (physical inactivity, ever smoking, and not consuming
      alcohol) were used to predict nursing home admission in pooled logistic
      regression models. We evaluated whether estimated effects of modifiable factors
      varied by dementia risk, comparing both relative and absolute effects using
      interaction terms between dementia risk and each modifiable risk factor. RESULTS:
      Low dementia probability was associated with lower nursing home admission risk
      (RR=0.49; 95% CI: 0.41, 0.59). Physical inactivity (RR=1.27; 95% CI: 1.15, 1.41),
      ever smoking (RR=1.12; 95% CI: 1.01, 1.25), and not consuming alcohol (RR=1.28;
      95% CI: 1.13, 1.45) predicted increased relative risk of nursing home admission
      regardless of cognitive status. The relative effects of modifiable risk factors
      were similar for those with low and high dementia risk. CONCLUSION: Although
      cognitive impairment associated with incipient dementia strongly predicts nursing
      home admission, this risk can be partially ameliorated with modifiable risk
      factors such as physical activity.

PMID- 27023176
TI  - Nature and nurture: environmental influences on a genetic rat model of
      depression.
AB  - In this study, we sought to learn whether adverse events such as chronic
      restraint stress (CRS), or 'nurture' in the form of environmental enrichment
      (EE), could modify depression-like behavior and blood biomarker transcript levels
      in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a
      genetic model of depression that aided in the identification of blood
      transcriptomic markers, which successfully distinguished adolescent and adult
      subjects with major depressive disorders from their matched no-disorder controls.
      Here, we followed the effects of CRS and EE in adult male WMIs and their
      genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that
      does not show depression-like behavior, by measuring the levels of these
      transcripts in the blood and hippocampus. In WLIs, increased depression-like
      behavior and transcriptomic changes were present in response to CRS, but in WMIs
      no behavioral or additive transcriptomic changes occurred. Environmental
      enrichment decreased both the inherent depression-like behavior in the WMIs and
      the behavioral difference between WMIs and WLIs, but did not reverse basal
      transcript level differences between the strains. The inverse behavioral change
      induced by CRS and EE in the WLIs did not result in parallel inverse expression
      changes of the transcriptomic markers, suggesting that these behavioral responses
      to the environment work via separate molecular pathways. In contrast, 'trait'
      transcriptomic markers with expression differences inherent and unchanging
      between the strains regardless of the environment suggest that in our model,
      environmental and genetic etiologies of depression work through independent
      molecular mechanisms. 

PMID- 27023178
TI  - ECT Investigator's Award.

PMID- 27023179
TI  - Swept-Source Optical Coherence Tomography Angiography of Paediatric Macular
      Diseases.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) angiography (OCTA)
      features of paediatric macular pathologies. METHODS: Retrospective serial case
      reports of patients who underwent routine clinical examination and OCTA of the
      posterior pole using both a DRI OCT Atlantis prototype and Triton Swept-Source
      OCT. When considered necessary, imaging was performed using Optos wide-field
      imaging or another non-invasive imaging system. The findings were compared with
      the current literature. RESULTS: Three cases with X-linked retinoschisis, 2 with
      epiretinal membrane, 1 with Best disease and 2 with Coats disease are fully
      illustrated. CONCLUSION: OCTA is an effective, non-invasive imaging technique
      that can offer additional information regarding the morphologies and vascular
      characteristics of macular lesions in paediatric ophthalmology. Because of the
      rarity and characteristics of many paediatric macular pathologies, further multi
      centric research is required with regard to the utilisation and features of OCTA
      imaging.

PMID- 27023175
TI  - Genome-wide association study of lifetime cannabis use based on a large meta
      analytic sample of 32 330 subjects from the International Cannabis Consortium.
AB  - Cannabis is the most widely produced and consumed illicit psychoactive substance
      worldwide. Occasional cannabis use can progress to frequent use, abuse and
      dependence with all known adverse physical, psychological and social
      consequences. Individual differences in cannabis initiation are heritable (40
      48%). The International Cannabis Consortium was established with the aim to
      identify genetic risk variants of cannabis use. We conducted a meta-analysis of
      genome-wide association data of 13 cohorts (N=32 330) and four replication
      samples (N=5627). In addition, we performed a gene-based test of association,
      estimated single-nucleotide polymorphism (SNP)-based heritability and explored
      the genetic correlation between lifetime cannabis use and cigarette use using LD
      score regression. No individual SNPs reached genome-wide significance.
      Nonetheless, gene-based tests identified four genes significantly associated with
      lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported
      associations of NCAM1 with cigarette smoking and other substance use, and those
      of CADM2 with body mass index, processing speed and autism disorders, which are
      phenotypes previously reported to be associated with cannabis use. Furthermore,
      we showed that, combined across the genome, all common SNPs explained 13-20%
      (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong
      genetic correlation (rg=0.83; P=1.85 * 10(-8)) between lifetime cannabis use and
      lifetime cigarette smoking implying that the SNP effect sizes of the two traits
      are highly correlated. This is the largest meta-analysis of cannabis GWA studies
      to date, revealing important new insights into the genetic pathways of lifetime
      cannabis use. Future functional studies should explore the impact of the
      identified genes on the biological mechanisms of cannabis use.

PMID- 27023181
TI  - Influences of Substrate Adhesion and Particle Size on the Shape Memory Effect of
      Polystyrene Particles.
AB  - Formulations and applications of micro- and nanoscale polymer particles have
      proliferated rapidly in recent years, yet knowledge of their mechanical behavior
      has not grown accordingly. In this study, we examine the ways that compressive
      strain, substrate surface energy, and particle size influence the shape memory
      cycle of polystyrene particles. Using nanoimprint lithography, differently sized
      particles are programmed into highly deformed, temporary shapes in contact with
      substrates of differing surface energies. Atomic force microscopy is used to
      obtain in situ measurements of particle shape recovery kinetics, and scanning
      electron microscopy is employed to assess differences in the profiles of
      particles at the conclusion of the shape memory cycle. Finally, finite element
      models are used to investigate the growing impact of surface energies at smaller
      length scales. Results reveal that the influence of substrate adhesion on
      particle recovery is size-dependent and can become dominating at submicron length
      scales. 

PMID- 27023180
TI  - TCR and IL-7 Signaling Are Altered in the Absence of Functional GTPase of the
      Immune Associated Nucleotide Binding Protein 5 (GIMAP5).
AB  - GTPase of the immune associated nucleotide binding protein (GIMAP) family of
      proteins are expressed essentially in cells of the hematopoietic system. Mutation
      in the founding member of this gene family, Gimap5, results in the lymphopenic
      phenotype in Bio-Breeding diabetes prone rats. In mice, deletion of functional
      Gimap5 gene affects the survival and renewal of hematopoietic stem cells in
      addition to the defects observed in T cells. Here we show that T cells from OTII
      TCR-transgenic Gimap5sph/sph mice do not proliferate in response to its cognate
      antigen. Furthermore, T cells from Gimap5 mutant rats and mice show decreased
      phosphorylation of STAT5 following stimulation with IL-7. Our results suggest
      that functional Gimap5 is required for optimal signaling through TCR and IL-7R in
      T cells. 

PMID- 27023182
TI  - The Scientific Impact of Developing Nations.
AB  - This paper analyzes science productivity for nine developing countries. Results
      show that these nations are reducing their science gap, with R&D investments and
      scientific impact growing at more than double the rate of the developed world.
      But this "catching up" hides a very uneven picture among these nations,
      especially on what they are able to generate in terms of impact and output
      relative to their levels of investment and available resources. Moreover, unlike
      what one might expect, it is clear that the size of the nations and the relative
      scale of their R&D investments are not the key drivers of efficiency. 

PMID- 27023183
TI  - Management Strategy Evaluation Applied to Coral Reef Ecosystems in Support of
      Ecosystem-Based Management.
AB  - Ecosystem modelling is increasingly used to explore ecosystem-level effects of
      changing environmental conditions and management actions. For coral reefs there
      has been increasing interest in recent decades in the use of ecosystem models for
      evaluating the effects of fishing and the efficacy of marine protected areas.
      However, ecosystem models that integrate physical forcings, biogeochemical and
      ecological dynamics, and human induced perturbations are still underdeveloped. We
      applied an ecosystem model (Atlantis) to the coral reef ecosystem of Guam using a
      suite of management scenarios prioritized in consultation with local resource
      managers to review the effects of each scenario on performance measures related
      to the ecosystem, the reef-fish fishery (e.g., fish landings) and coral habitat.
      Comparing tradeoffs across the selected scenarios showed that each scenario
      performed best for at least one of the selected performance indicators. The
      integrated 'full regulation' scenario outperformed other scenarios with four out
      of the six performance metrics at the cost of reef-fish landings. This model
      application quantifies the socio-ecological costs and benefits of alternative
      management scenarios. When the effects of climate change were taken into account,
      several scenarios performed equally well, but none prevented a collapse in coral
      biomass over the next few decades assuming a business-as-usual greenhouse gas
      emissions scenario. 

PMID- 27023184
TI  - How Medical Education Can Add Value to the Health Care Delivery System.

PMID- 27023185
TI  - Additional Considerations for the Expert-Generalist Model.

PMID- 27023186
TI  - Additional Considerations for the Expert-Generalist Model.

PMID- 27023187
TI  - In Reply to Volpintesta and to Schwenk et al.

PMID- 27023188
TI  - Advocacy Training as a Complement to Instruction About Health Disparities.

PMID- 27023189
TI  - Hurdles to Legislative Advocacy Training in the United States.

PMID- 27023190
TI  - In Reply to Pivalizza et al.

PMID- 27023191
TI  - Poor Relations: Social Scientists and Medical Education.

PMID- 27023192
TI  - In Reply to McKendree.

PMID- 27023193
TI  - Soliciting Patient Feedback on Visit Notes: An Educational Opportunity.

PMID- 27023194
TI  - When Patients Teach.

PMID- 27023195
TI  - Artists' Statement: A Patient's Perspective.

PMID- 27023196
TI  - Medicine and the Arts. In the Country of Hearts: Journeys in the Art of Medicine:
      [Excerpt] by John Stone. Commentary.

PMID- 27023198
TI  - Clarity of Vision.

PMID- 27023199
TI  - Enantioselective Intermolecular Enamide-Aldehyde Cross-Coupling Catalyzed by
      Chiral N-Heterocyclic Carbenes.
AB  - The unprecedented N-heterocyclic carbene (NHC)-catalyzed intermolecular cross
      coupling of enamides and aldehydes is described. Upon exposure of enamides to
      aldehydes in the presence of a NHC catalyst, catalytic C-C bond formation occurs,
      providing highly enantioselective N-protected amines, bearing a quaternary carbon
      center, in good yields and with high enantioselectivities. 

PMID- 27023200
TI  - Diel Surface Temperature Range Scales with Lake Size.
AB  - Ecological and biogeochemical processes in lakes are strongly dependent upon
      water temperature. Long-term surface warming of many lakes is unequivocal, but
      little is known about the comparative magnitude of temperature variation at diel
      timescales, due to a lack of appropriately resolved data. Here we quantify the
      pattern and magnitude of diel temperature variability of surface waters using
      high-frequency data from 100 lakes. We show that the near-surface diel
      temperature range can be substantial in summer relative to long-term change and,
      for lakes smaller than 3 km2, increases sharply and predictably with decreasing
      lake area. Most small lakes included in this study experience average summer diel
      ranges in their near-surface temperatures of between 4 and 7 degrees C. Large
      diel temperature fluctuations in the majority of lakes undoubtedly influence
      their structure, function and role in biogeochemical cycles, but the full
      implications remain largely unexplored. 

PMID- 27023201
TI  - Quantification of sound instability in embouchure tremor based on the time
      varying fundamental frequency.
AB  - Task-specific tremor in musicians is an involuntary oscillating muscular activity
      mostly of the hand or the embouchure, which predominantly occurs while playing
      the instrument. In contrast to arm or hand tremors, which have been examined and
      objectified based on movement kinematics and muscular activity, embouchure tremor
      has not yet been investigated. To quantify and describe embouchure tremor we
      analysed sound production and investigated the fluctuation of the time-varying
      fundamental frequency of sustained notes. A comparison between patients with
      embouchure tremor and healthy controls showed a significantly higher fluctuation
      of the fundamental frequency for the patients in the high pitch with a tremor
      frequency range between 3 and 8 Hz. The present findings firstly provide further
      information about a scarcely described movement disorder and secondly further
      evaluate a new quantification method for embouchure tremor, which has recently
      been established for embouchure dystonia.

PMID- 27023203
TI  - Estimation of the Intestinal Absorption and Metabolism Behaviors of 2- and 3
      Monochloropropanediol Esters.
AB  - The regioisomers of the di- and mono-oleate of monochloropropanediol (MCPD) have
      been synthesized and subsequently hydrolyzed with pancreatic lipase and
      pancreatin to estimate the intestinal digestion and absorption of these compounds
      after their intake. The hydrolysates were analyzed by HPLC using a corona charged
      aerosol detection system, which allowed for the separation and detection of the
      different regioisomers of the MCPD esters. The hydrolysates were also analyzed by
      GC-MS to monitor the free MCPD. The results indicated that the two acyl groups of
      2-MCPD-1,3-dioleate were smoothly hydrolyzed by pancreatic lipase and pancreatin
      to give free 2-MCPD. In contrast, the hydrolysis of 3-MCPD-1,2-dioleate proceeded
      predominantly at the primary position to produce 3-MCPD-2-oleate. 2-MCPD-1-oleate
      and 3-MCPD-1-oleate were further hydrolyzed to free 2- and 3-MCPD by pancreatic
      lipase and pancreatin, although the hydrolysis of 3-MCPD-2-oleate was 80 % slower
      than that of 3-MCPD-1-oleate. The intestinal absorption characteristics of these
      compounds were evaluated in vitro using a Caco-2 cell monolayer. The results
      revealed that the MCPD monooleates, but not the MCPD dioleates, were hydrolyzed
      to produce the free MCPD in the presence of the Caco-2 cells. The resulting free
      MCPD permeated the Caco-2 monolayer most likely via a diffusion mechanism because
      their permeation profiles were independent of the dose. Similar permeation
      profiles were obtained for 2- and 3-MCPDs.

PMID- 27023202
TI  - Dietary Lipid and Carbohydrate Interactions: Implications on Lipid and Glucose
      Absorption, Transport in Gilthead Sea Bream (Sparus aurata) Juveniles.
AB  - A digestibility trial was performed with gilthead sea bream juveniles (IBW = 72
      g) fed four diets differing in lipid source (fish oil, FO; or a blend of
      vegetable oil, VO) and starch content (0 %, CH-; or 20 %, CH+) to evaluate the
      potential interactive effects between carbohydrates and VO on the processes
      involved in digestion, absorption and transport of lipids and glucose. In fish
      fed VO diets a decrease in lipid digestibility and in cholesterol (C), High
      Density Lipoprotein(HDL)-C and Low Density Lipoprotein (LDL)-C (only in CH+
      group) were recorded. Contrarily, dietary starch induced postprandial
      hyperglycemia and time related alterations on serum triacylglycerol (TAG),
      phospholipid (PL) and C concentrations. Fish fed a CH+ diet presented lower serum
      TAG than CH- group at 6 h post-feeding, and the reverse was observed at 12 h post
      feeding for TAG and PL. Lower serum C and PL at 6 h post-feeding were recorded
      only in VOCH+ group. No differences between groups were observed in hepatic and
      intestinal transcript levels of proteins involved in lipid transport and
      hydrolysis (FABP, DGAT, GPAT, MTP, LPL, LCAT). Lower transcript levels of
      proteins related to lipid transport (ApoB, ApoA1, FABP2) were observed in the
      intestine of fish fed the CH+ diet, but remained unchanged in the liver. Overall,
      transcriptional mechanisms involved in lipid transport and absorption were not
      linked to changes in lipid serum and digestibility. Dietary starch affected lipid
      absorption and transport, probably due to a delay in lipid absorption. This study
      suggests that a combination of dietary VO and starch may negatively affect
      cholesterol absorption and transport.

PMID- 27023204
TI  - Impressions of pharmacogenomic testing among Certified Registered Nurse
      Anesthetists: a mixed-method study.
AB  - AIM: Pharmacogenomic testing is useful in helping to predict and explain patient
      responsiveness to medication. In clinical practice, the use of pharmacogenomic
      testing has been shown to help reduce adverse drugs events and increase patient
      satisfaction with their healthcare. Prior to a test being useful, it must have
      clinical utility. There is a gap in the literature about the perceived clinical
      utility of pharmacogenomic testing among anesthesia providers. METHODS: This
      qualitative-quantitative sequential mixed-method study used focused interviews to
      formulate probes for a quantitative survey aimed at quantifying the perceptions
      of anesthesia providers about pharmacogenomic testing. RESULTS: The results
      indicate anesthesia providers do not have enough knowledge about pharmacogenomic
      testing for it to be considered clinically useful in anesthesia practice.
      CONCLUSION: Although outcomes data indicate pharmacogenomic testing can help
      predict outcomes, anesthesia providers do not have enough knowledge and have
      concerns about the ethical implications of pharmacogenomic testing.

PMID- 27023206
TI  - Human Interactive Triboelectric Nanogenerator as a Self-Powered Smart Seat.
AB  - A lightweight, flexible, cost-effective, and robust, single-electrode-based Smart
      Seat-Triboelectric Nanogenerator (SS-TENG) is introduced as a promising eco
      friendly approach for harvesting energy from the living environment, for use in
      integrated self-powered systems. An effective method for harvesting biomechanical
      energy from human motion such as walking, running, and sitting, utilizing widely
      adaptable everyday contact materials (newspaper, denim, polyethylene covers, and
      bus cards) is demonstrated. The working mechanism of the SS-TENG is based on the
      generation and transfer of triboelectric charge carriers between the active layer
      and user-friendly contact materials. The performance of SS-TENG (52 V and 5.2 MUA
      for a multiunit SS-TENG) is systematically studied and demonstrated in a range of
      applications including a self-powered passenger seat number indicator and a STOP
      indicator using LEDs, using a simple logical circuit. Harvested energy is used as
      a direct power source to drive 60 blue and green commercially available LEDs and
      a monochrome LCD. This feasibility study confirms that triboelectric
      nanogenerators are a suitable technology for energy harvesting from human motion
      during transportation, which could be used to operate a variety of wireless
      devices, GPS systems, electronic devices, and other sensors during travel. 

PMID- 27023205
TI  - Diagnostic Accuracy of Antigen 5-Based ELISAs for Human Cystic Echinococcosis.
AB  - BACKGROUND: Clinical diagnosis and follow up of cystic echinococcosis (CE) are
      based on imaging complemented by serology. Several immunodiagnostic tests are
      commercially available, but the development of new tools is still needed to
      overcome the lack of standardization of the target antigen, generally consisting
      of a crude extract of Echinococcus granulosus hydatid cyst fluid. In a previous
      work, we described a chromatographic method for the preparation of a highly
      enriched Antigen 5 fraction from hydatid cyst fluid. The high reactivity of
      patient sera against this preparation prompted us to evaluate further this
      antigen for the serodiagnosis of CE on a larger cohort of samples.
      METHODOLOGY/PRINCIPAL FINDINGS: A total of 327 sera from CE patients with
      heterogeneous conditions for cyst stage, cyst number, organ localization, drug
      therapy, and surgical intervention, together with 253 sera from healthy controls,
      were first analyzed by an ELISA based on the Ag5 preparation in two different
      experimental setups and, in parallel, by a commercial ELISA routinely used in
      clinical laboratories for CE serodiagnosis. The Ag5 ELISAs revealed different
      sensitivity (88.3% vs 95.3%) without significant differences in specificity
      (94.1% vs 92.5%), for the two setups, respectively. Moreover, possible
      relationships between the Ag5 ELISA absorbance results and clinical variables
      were investigated. Chi squared test, bivariate logistic regression and multiple
      regression analyses highlighted differences in the serology reactivity according
      to pharmacological treatment, cyst activity, and cyst number.
      CONCLUSIONS/SIGNIFICANCE: The two Ag5 ELISAs revealed different performances
      depending on the setup. The good diagnostic sensitivity and the high reliability
      of the Ag5 preparation method make this antigen a promising candidate for the
      serodiagnosis of CE. Further studies will be needed to evaluate the ability of
      our test to provide useful information on specific CE clinical traits.

PMID- 27023207
TI  - Economic Thresholds in Soybean-Integrated Pest Management: Old Concepts, Current
      Adoption, and Adequacy.
AB  - Increasing global demands for food underline the need for higher crop yields. The
      relatively low costs of the most commonly used insecticides in combination with
      increasing soybean market prices led growers and technical advisors to debate the
      adequacy of recommended economic thresholds (ETs). The adoption of ETs and pest
      sampling has diminished in Brazil, leading to excessive pesticide use on soybean.
      The reduced efficacy of natural biological control, faster pest resurgence, and
      environment contamination are among the side-effects of pesticide abuse. To
      address these problems and maximize agricultural production, pest control
      programs must be guided by a proper integrated pest management (IPM) approach,
      including the ET concept. Therefore, the most appropriate time to initiate
      insecticide spraying in soybean is indicated by the available ETs which are
      supported by experiments over the last 40 years in different edapho-climatic
      conditions and regions with distinct soybean cultivars. Published scientific data
      indicate that preventive insecticide use is an expensive and harmful use of
      chemicals that increases the negative impact of pesticides in agroecosystems.
      However, the established ETs are for a limited number of species (key pests), and
      they only address the use of chemicals. There is a lack of information regarding
      secondary pests and other control strategies in addition to insecticides. It is
      clear then that much progress is still needed to improve ETs for pest management
      decisions. Nevertheless, using the current ETs provides a basis for reducing the
      use of chemicals in agriculture without reducing yields and overall production,
      thereby improving sustainability. 

PMID- 27023208
TI  - A Third Species of Hemilecanium Newstead (Hemiptera: Coccoidea: Coccidae) from
      the New World, with Keys to Species in the Genus.
AB  - A new species of Hemilecanium Newstead, Hemilecanium guanabana Kondo & Hodgson n.
      sp., is described and illustrated based on the adult female, adult male and first
      instar. The specimens were collected in the municipality of Palmira, state of
      Valle del Cauca, Colombia, on soursop, Annona muricata (Annonaceae). Updated
      identification keys are provided for the adult females of all 28 species of the
      genus Hemilecanium, and for known adult males and first instars. An updated list
      of the 23 species of soft scales (Coccidae) known from soursop worldwide is
      included. 

PMID- 27023209
TI  - Storage of Pentatomid Eggs in Liquid Nitrogen and Dormancy of Trissolcus basalis
      (Wollaston) and Telenomus podisi Ashmead (Hymenoptera: Platygastridae) Adults as
      a Method of Mass Production.
AB  - The eggs of pentatomid species were evaluated to parasitism by Trissolcus basalis
      (Wollaston) and Telenomus podisi Ashmead after storage in liquid nitrogen. Adults
      which emerged from stored eggs were kept at 18 degrees C for 120 and 180 days to
      investigate whether adult dormancy could be associated with host egg storage in
      liquid nitrogen as a method of mass production of these egg parasitoids. Eggs of
      Nezara viridula (L.) and Acrosternum pengue (Rolston) were successfully
      parasitized by T. basalis, as well as Piezodorus guildinii (Westwood) and
      Dichelops furcatus (F.) by T. podisi. The eggs of Edessa meditabunda (F.) were
      not parasitized by T. basalis. The emergence of T. podisi from eggs of Euschistus
      heros (F.) and Podisus nigrispinus (Dallas) stored for 6 months was lower than
      the control. Females of T. basalis and T. podisi that emerged from stored eggs
      were kept in dormancy at 18 degrees C. Longevity of T. basalis was influenced by
      the storage time and sex, but not by the interaction of sex and storage time. For
      T. podisi, longevity was influenced by the storage time, sex, and by the
      interaction of sex and storage time. For T. basalis, storage in liquid nitrogen
      did not affect the fecundity of quiescent females, while the number of
      parasitized eggs by T. podisi decreased after storage. By the joint use of these
      techniques, it is possible to optimize mass production of T. basalis so that its
      life cycle can be monitored and synchronized with the life cycle and availability
      of hosts. 

PMID- 27023210
TI  - Population Growth and Damage Caused by Rhopalosiphum padi (L.) (Hemiptera,
      Aphididae) on Different Cultivars and Phenological Stages of Wheat.
AB  - Among the aphids associated with wheat and other winter cereals, Rhopalosiphum
      padi (L.) is currently the predominant species in the wheat growing region of
      southern Brazil. The damage caused by this aphid occurs by direct feeding and/or
      by the transmission of pathogenic viruses, such as the Barley/Cereal yellow dwarf
      virus. In order to estimate the direct damage caused by R. padi on wheat, we
      evaluated the population growth of this aphid during the tillering and elongation
      stages and its effects on grain yield components. The experiment was conducted in
      a screenhouse with three wheat cultivars (BRS Guabiju, BRS Timbauva, and Embrapa
      16). The effect of a period of 16 days, starting from an infestation of 40
      aviruliferous aphids/plant, was evaluated and compared to non-infested plants. In
      both stages, the population growth of R. padi was lower on the BRS Timbauva.
      Although infestation caused a reduction in the grain yield of the three
      cultivars, this effect was lower for BRS Timbauva. The cultivar Embrapa 16
      supported higher infestations and was more tolerant to damage than the BRS
      Guabiju. 

PMID- 27023211
TI  - Parental Whole Life Cycle Exposure to Dietary Methylmercury in Zebrafish (Danio
      rerio) Affects the Behavior of Offspring.
AB  - Methylmercury (MeHg) is an established neurotoxicant of concern to fish-eating
      organisms. While most studies have focused on the fish consumers, much less is
      known about the effects of MeHg on the fish themselves, especially following
      exposures to chronic and environmentally relevant scenarios. Here we evaluated
      the behavioral effects of developmental MeHg insult by exposing parental
      generations of zebrafish to an environmentally realistic MeHg dietary
      concentration (1 ppm) and two higher concentrations (3 and 10 ppm) throughout
      their whole life span. Upon reaching adulthood, their offspring were analyzed
      through a series of behavioral tests, including the visual-motor response (VMR)
      assay, analysis of spontaneous swimming and evaluation of foraging efficiency.
      The VMR assay identified decreased locomotor output in the 6 day
      postfertilization (dpf) offspring of fish exposed to 3 and 10 ppm MeHg. However,
      in a second test 7 dpf fish revealed an increase in locomotor activity in all
      MeHg exposures tested. Increases in locomotion continued to be observed until 16
      dpf, which coincided with increased foraging efficiency. These results suggest an
      association between MeHg and hyperactivity, and imply that fish chronically
      exposed to MeHg in the wild may be vulnerable to predation.

PMID- 27023212
TI  - Synthesis of the (9R,13R)-isomer of LDS1, a flower-inducing oxylipin isolated
      from Lemna paucicostata.
AB  - The first synthesis of the (9R,13R)-stereoisomer of LDS1, a flower-inducing
      oxylipin isolated from Lemna paucicostata, has been achieved from a known allylic
      alcohol by a seven-step sequence that involves the Horner-Wadsworth-Emmons
      olefination to construct its full carbon framework and an enzymatic hydrolysis of
      a penultimate methyl ester intermediate to provide the target molecule. 

PMID- 27023213
TI  - Comparative Yield of Different Diagnostic Tests for Tuberculosis among People
      Living with HIV in Western Kenya.
AB  - BACKGROUND: Diagnosis followed by effective treatment of tuberculosis (TB)
      reduces transmission and saves lives in persons living with HIV (PLHIV). Sputum
      smear microscopy is widely used for diagnosis, despite limited sensitivity in
      PLHIV. Evidence is needed to determine the optimal diagnostic approach for these
      patients. METHODS: From May 2011 through June 2012, we recruited PLHIV from 15
      HIV treatment centers in western Kenya. We collected up to three sputum specimens
      for Ziehl-Neelsen (ZN) and fluorescence microscopy (FM), GeneXpert MTB/RIF
      (Xpert), and culture, regardless of symptoms. We calculated the incremental yield
      of each test, stratifying results by CD4 cell count and specimen type; data were
      analyzed to account for complex sampling. RESULTS: From 778 enrolled patients, we
      identified 88 (11.3%) laboratory-confirmed TB cases. Of the 74 cases who
      submitted 2 specimens for microscopy and Xpert testing, ZN microscopy identified
      25 (33.6%); Xpert identified those plus an additional 18 (incremental yield =
      24.4%). Xpert testing of spot specimens identified 48 (57.0%) of 84 cases;
      whereas Xpert testing of morning specimens identified 50 (66.0%) of 76 cases. Two
      Xpert tests detected 22/24 (92.0%) TB cases with CD4 counts <100 cells/MUL and
      30/45 (67.0%) of cases with CD4 counts >=100 cells/MUl. CONCLUSIONS: In PLHIV,
      Xpert substantially increased diagnostic yield compared to smear microscopy and
      had the highest yield when used to test morning specimens and specimens from
      PLHIV with CD4 count <100 cells/MUL. TB programs unable to replace smear
      microscopy with Xpert for all symptomatic PLHIV should consider targeted
      replacement and using morning specimens.

PMID- 27023214
TI  - Optical Coherence Tomography Angiography of Dry Age-Related Macular Degeneration.
AB  - Optical coherence tomography angiography (OCTA) can be used to visualize
      alterations in the choriocapillaris of patients with dry age-related macular
      degeneration (AMD). These changes seem to be present during all stages of the
      disease. Earlier stages are associated with patchy thinning of the
      choriocapillaris, while geographic atrophy is associated with loss of
      choriocapillaris lying under the area of geographic atrophy and asymmetric
      alteration of choriocapillaris at the margins of the geographic atrophy. The use
      of high-speed, long-wave-length swept-source OCT for angiography, with its better
      penetration into the choroid and high acquisition speeds, enable OCTA with scaled
      slowest detectable flow and fastest distinguishable flow. This will enable us to
      better investigate choriocapillaris changes in patients with dry AMD. The ability
      to image the choriocapillaris structure and flow impairments may be useful in the
      future for detecting and monitoring the progression of dry AMD and for monitoring
      treatment responses in clinical trials to therapies that target disease
      progression in dry AMD. 

PMID- 27023215
TI  - The diagnostic role of the neutrophil-to-lymphocyte ratio in predicting
      pancreatic ductal adenocarcinoma in patients with pancreatic diseases.
AB  - BACKGROUND: Accurately diagnosing pancreatic ductal adenocarcinomas (PDACs) is
      challenging because of the loss of vascularity and poor imaging. The neutrophil
      to-lymphocyte ratio (NLR) has been reported to predict poor prognosis in several
      types of malignancy including PDAC; however, the diagnostic role of NLR in PDAC
      has never been addressed. METHODS: This study retrospectively assessed 297
      patients who underwent curative pancreatic resection for pancreatic tumors from
      1995-2015, including 140 with PDACs, 58 with pancreatic neuroendocrine tumors
      (PNETs), 76 with intraductal papillary mucinous neoplasms (IPMNs), 13 with
      mucinous/serous cyst neoplasms, 7 with solid pseudopapillary neoplasms, and 3
      with tumor-forming pancreatitis. The role of preoperative NLR in predicting PDACs
      was investigated. RESULTS: Preoperative NLR was significantly higher in patients
      with PDACs (2.52 +/- 1.34) than in patients with PNETs (1.93 +/- 0.68, P =
      0.0004) and IPMNs (2.17 +/- 0.79, P = 0.0253). Only eight patients with PDACs
      (5.7 %) had NLR >5; of these, three had normal carcinoembyronic antigen (CEA) and
      carbohydrate antigen 19-9 (CA19-9) levels. Multivariate analysis revealed that
      abnormal CA19-9 levels, abnormal CEA levels, age >67 years, and NLR >5 were
      independent predictors of PDACs. Both the specificity and the positive predictive
      value of NLR >5 for predicting PDACs were 100 %; however, the sensitivity was 4.6
      % and the negative predictive value was 43.8 %. CONCLUSIONS: NLR >5 could
      independently predict the occurrence of PDACs in pancreatic neoplastic disease
      irrespective of other tumor markers, CEA and CA19-9, in pancreatic disease.

PMID- 27023216
TI  - Self-Assembled ROS-Sensitive Polymer-Peptide Therapeutics Incorporating Built-in
      Reporters for Evaluation of Treatment Efficacy.
AB  - One of the major challenges in current cancer therapy is to maximize therapeutic
      effect and evaluate tumor progression under the scheduled treatment protocol. To
      address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named
      KLAK) conjugated amphiphilic poly(beta-thioester)s copolymers (H-P-K) composed of
      reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene
      glycol (PEG) side chains. H-P-K could self-assemble into micelle-like
      nanoparticles by hydrophobic interaction with copolymer backbones as cores and
      PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably
      improved cellular internalization and accumulation of therapeutic KLAK in cells.
      Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly
      enhanced up to ~400 times, suggesting the effectiveness of the nanoscaled polymer
      peptide conjugation as biopharmaceuticals. The higher antitumor activity of
      nanoparticles was attributed to the efficient disruption of mitochondrial
      membranes and subsequent excessive ROS production in cells. To realize the ROS
      monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built
      in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around
      mitochondria stimulated the swelling of nanoparticles and subsequent release of
      SQ, which formed H-aggregates and significantly increased the photoacoustic (PA)
      signal. We believed that this self-assembled polymer-peptide nanotherapeutics
      incorporating built-in reporters has great potential for high antitumor
      performance and in situ treatment evaluation.

PMID- 27023217
TI  - Major hepatopancreatoduodenectomy with simultaneous resection of the hepatic
      artery for advanced biliary cancer.
AB  - BACKGROUND: Major hepatopancreatoduodenectomy (HPD) with simultaneous resection
      of the hepatic artery (HA) for biliary cancer is the most extended surgery for
      obtaining curative resection, and its clinical significance is unclear. The aim
      of this study was to appraise the clinical value of this extended procedure as a
      treatment for biliary cancer. METHODS: We retrospectively reviewed the medical
      records of 38 patients with biliary cancer who underwent major HPD from 1994 to
      2014. Clinicopathological factors and survival following HPD were compared
      between patients with and without simultaneous resection of the HA. RESULTS: Of
      the 38 study patients, 12 patients (32 %) underwent major HPD with HA. There was
      no significant difference in major complications between the two groups. The
      overall 2-year survival rate and the median survival time following major HPD
      with HA were 71 % and 42.3 months. The survival of the patients with gallbladder
      cancer was significantly worse than that of the patients with bile duct cancer (p
      = 0.001). CONCLUSIONS: Major HPD with simultaneous resection of the HA can be a
      preferable treatment option for bile duct cancer that offers acceptable
      perioperative morbidity and mortality, as well as long-term survival. However,
      this procedure for gallbladder cancer should not be performed.

PMID- 27023218
TI  - Routine ultrasound and blood tests after laparoscopic cholecystectomy-are they
      worthwhile? A diagnostic accuracy study.
AB  - PURPOSE: Delayed recognition of complications can have life-threatening sequelae
      and is a leading cause of medical litigation. Minimal evidence exists for
      benefits of postoperative surveillance. This study investigated whether
      ultrasound (US) and blood tests can detect complications after laparoscopic
      cholecystectomy. METHODS: A series of 772 laparoscopic cholecystectomies
      performed between February 2008 and October 2009 was retrospectively analyzed.
      Routine US was performed within 6 h postoperatively, and a blood sample was taken
      at the second postoperative day. RESULTS: Postoperative US was performed in 722
      patients. Fluid accumulation was documented in 104 patients; only two of these
      patients had clinically significant findings requiring treatment. The best
      predictor of infectious complications was elevated postoperative C-reactive
      protein (>=123 mg/L), with an area under the curve (AUC) of 0.94 and a number
      needed to misdiagnose (NNM) of 8.7. To predict postoperative choledocholithiasis,
      a combination of total bilirubin, aspartate aminotransferase and alkaline
      phosphatase elevations, with cutoff values of 1.3 mg/dL, 37 IU/L, and 136 IU/L,
      respectively, attained the highest accuracy with a NNM of 29.5. Ultrasonographic
      detection of bile duct dilation further improved specificity, while lowering
      sensitivity. CONCLUSIONS: The value of early routine postoperative US is low,
      unless there is clinical suspicion of complications. Routine blood tests have a
      high sensitivity for infectious complications and a high specificity for remnant
      biliary duct stones. Therefore, we recommend avoiding routine US postoperatively
      and performing routine postoperative blood tests. We also recommend facilitating
      easy access to postoperative US, as it can aid the decision to take therapeutic
      measures in symptomatic patients.

PMID- 27023219
TI  - Competitive immunosensor based on gliadin immobilization on disposable carbon
      nanogold screen-printed electrodes for rapid determination of celiotoxic
      prolamins.
AB  - The first competitive disposable amperometric immunosensor based on gliadin
      functionalized carbon/nanogold screen-printed electrodes was developed for rapid
      determination of celiotoxic prolamins. To date, no competitive spectrophotometric
      or electrochemical immunoassays have yet been successfully applied to gluten
      detection in processed food samples, which require the use of complex prolamin
      extraction solutions containing additives with denaturing, reducing and
      disaggregating functions. Thus, in this work, great effort was put into the
      optimization and performance evaluation of the immunosensor in terms of
      suitability as a screening tool for analysis of cereal-based food samples. For
      this purpose, aqueous ethanol or complex extraction mixtures, as the patented
      Cocktail Solution(r), were proved effective in the extraction of gliadin. Good
      sensitivity was achieved after optimization of the immunocompetitive assay,
      giving limit of detection and limit of quantitation of 8 and 22 ng/ml of gliadin,
      respectively, for ethanol extracts. The immunosensor was proved to be suitable
      also for samples extracted with Cocktail Solution(r) after a proper dilution.
      Analysis of real samples of different flours proved the suitability of the
      immunosensing device as a powerful tool for safety assessment of raw materials
      used for the formulation of dietary products for celiac disease patients. This
      immunosensor combines good analytical performance using a very simplified set-up
      protocol with suitability for rapid screening analysis performed using
      inexpensive and portable instrumentation. Graphical abstract Depiction of the
      development and working principle of the competitive immunosensor. 

PMID- 27023220
TI  - An ascorbic acid sensor based on cadmium sulphide quantum dots.
AB  - We present a Forster resonance energy transfer (FRET)-based fluorescence
      detection of vitamin C [ascorbic acid (AA)] using cadmium sulphide quantum dots
      (CdS QDs) and diphenylcarbazide (DPC). Initially, DPC was converted to
      diphenylcarbadiazone (DPCD) in the presence of CdS QDs to form QD-DPCD. This
      enabled excited-state energy transfer from the QDs to DPCD, which led to the
      fluorescence quenching of QDs. The QD-DPCD solution was used as the sensor
      solution. In the presence of AA, DPCD was converted back to DPC, resulting in the
      fluorescence recovery of CdS QDs. This fluorescence recovery can be used to
      detect and quantify AA. Dynamic range and detection limit of this sensing system
      were found to be 60-300 nM and 2 nM, respectively. We also performed fluorescence
      lifetime analyses to confirm existence of FRET. Finally, the sensor responded
      with equal accuracy to actual samples such as orange juice and vitamin C tablets.
      Graphical abstract Schematic showing the FRET based fluorescence detection of
      ascorbic acid.

PMID- 27023221
TI  - Early life stress is a risk factor for excessive alcohol drinking and impulsivity
      in adults and is mediated via a CRF/GABA(A) mechanism.
AB  - Childhood stress and trauma are associated with substance use disorders in
      adulthood, but the neurological changes that confer increased vulnerability are
      largely unknown. In this study, maternal separation (MS) stress, restricted to
      the pre-weaning period, was used as a model to study mechanisms of protracted
      effects of childhood stress/traumatic experiences on binge drinking and
      impulsivity. Using an operant self-administration model of binge drinking and a
      delay discounting assay to measure impulsive-like behavior, we report that early
      life stress due to MS facilitated acquisition of binge drinking and impulsivity
      during adulthood in rats. Previous studies have shown heightened levels of
      corticotropin releasing factor (CRF) after MS, and here, we add that MS increased
      expression levels of GABA(A) alpha2 subunit in central stress circuits. To
      investigate the precise role of these circuits in regulating impulsivity and
      binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A)
      alpha2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and
      medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly
      reduced impulsivity and produced profound reductions on binge-motivated alcohol
      drinking, without altering responding for sucrose. Furthermore, whole-cell patch
      clamp studies showed that low concentrations of 3-PBC directly reversed the
      effect of relatively high concentrations of ethanol on alpha2beta3gamma2 GABA(A)
      receptors, by a benzodiazepine site-independent mechanism. Together, our data
      provide strong evidence that maternal separation, i.e. early life stress, is a
      risk factor for binge drinking, and is linked to impulsivity, another key risk
      factor for excessive alcohol drinking. We further show that pharmacological
      manipulation of CRF and GABA receptor signaling is effective to reverse binge
      drinking and impulsive-like behavior in MS rats. These results provide novel
      insights into the role of the brain stress systems in the development of
      impulsivity and excessive alcohol consumption.

PMID- 27023223
TI  - An Antagomir to MicroRNA-106b-5p Ameliorates Cerebral Ischemia and Reperfusion
      Injury in Rats Via Inhibiting Apoptosis and Oxidative Stress.
AB  - We previously observed that microRNA miR-106b-5p significantly increased in serum
      of patients with acute ischemic stroke. The present study was to determine
      whether miR-106b-5p antagomir can protect against cerebral ischemia/reperfusion
      (I/R) injury and elucidate its underlying mechanisms. Middle cerebral artery
      occlusion (MCAO) was operated on male Sprague Dawley rats. MiR-106b-5p antagomir
      significantly decreased neurological deficit scores, infarct volumes, and
      neuronal injury. Furthermore, miR-106b-5p antagomir markedly reduced
      malondialdehyde (MDA) content, restored superoxide dismutase (SOD) activity,
      increased the expression of myeloid cell leukemia-1 (Mcl-1) and B cell lymphoma-2
      (Bcl-2), and decreased the expression of Bax in the ischemic cortex. In PC12
      cells, miR-106b-5p inhibitor increased the Mcl-1 and Bcl-2 expression, which
      provided protection against glutamate-induced apoptosis and oxidative damage, as
      evidenced by decreased lactate dehydrogenase (LDH) release, and enhanced SOD
      activity. Notably, luciferase reported assay proved Mcl-1 was the target gene of
      miR-106b-5p. In conclusion, our data indicates that the neuroprotective effects
      of miR-106b-5p antagomir on cerebral I/R injury are associated with its
      inhibition of apoptosis and oxidative stress, suggesting a potential therapeutic
      target for ischemic stroke.

PMID- 27023224
TI  - Association of DISC1 Polymorphisms with Late-Onset Alzheimer's Disease in
      Northern Han Chinese.
AB  - The disrupted-in-schizophrenia-1 (DISC1) is a candidate gene for psychiatric
      diseases and plays various roles in brain development. It has been reported as a
      candidate gene for Alzheimer's disease (AD) in a recent large genome-wide
      association study in Caucasians. To explore the associations between DISC1 and
      AD, we performed a case-control study including 2318 subjects in Northern Han
      Chinese. We found that one single nucleotide polymorphism (rs6675281) was
      associated with the risk of late-onset Alzheimer's disease (LOAD) in northern Han
      Chinese population. As for rs821616 and rs3738401, no association was detected
      with LOAD. In conclusion, DISC1 increased the risk for LOAD in northern Han
      Chinese population.

PMID- 27023222
TI  - Is immunosenescence influenced by our lifetime "dose" of exercise?
AB  - The age-associated decline in immune function, referred to as immunosenescence,
      is well characterised within the adaptive immune system, and in particular, among
      T cells. Hallmarks of immunosenescence measured in the T cell pool, include low
      numbers and proportions of naive cells, high numbers and proportions of late
      stage differentiated effector memory cells, poor proliferative responses to
      mitogens, and a CD4:CD8 ratio <1.0. These changes are largely driven by infection
      with Cytomegalovirus, which has been directly linked with increased inflammatory
      activity, poor responses to vaccination, frailty, accelerated cognitive decline,
      and early mortality. It has been suggested however, that exercise might exert an
      anti-immunosenescence effect, perhaps delaying the onset of immunological ageing
      or even rejuvenating aged immune profiles. This theory has been developed on the
      basis of evidence that exercise is a powerful stimulus of immune function. For
      example, in vivo antibody responses to novel antigens can be improved with just
      minutes of exercise undertaken at the time of vaccination. Further, lymphocyte
      immune-surveillance, whereby cells search tissues for antigens derived from
      viruses, bacteria, or malignant transformation, is thought to be facilitated by
      the transient lymphocytosis and subsequent lymphocytopenia induced by exercise
      bouts. Moreover, some forms of exercise are anti-inflammatory, and if repeated
      regularly over the lifespan, there is a lower morbidity and mortality from
      diseases with an immunological and inflammatory aetiology. The aim of this
      article is to discuss recent theories for how exercise might influence T cell
      immunosenescence, exploring themes in the context of hotly debated issues in
      immunology.

PMID- 27023225
TI  - The Interaction of UDP-N-Acetylglucosamine 2-Epimerase/N-Acetylmannosamine Kinase
      (GNE) and Alpha-Actinin 2 Is Altered in GNE Myopathy M743T Mutant.
AB  - UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the gene
      mutated in GNE myopathy. In an attempt to elucidate GNE functions that could
      account for the muscle pathophysiology of this disorder, the interaction of GNE
      with alpha-actinins has been investigated. Surface plasmon resonance and
      microscale thermophoresis analysis revealed, that in vitro, GNE interacts with
      alpha-actinin 2, and that this interaction has a 10-fold higher affinity compared
      to the GNE-alpha-actinin 1 interaction. Further, GNE carrying the M743T mutation,
      the most frequent mutation in GNE myopathy, has a 10-fold lower binding affinity
      to alpha-actinin 2 than intact GNE. It is possible that this decrease eventually
      affects the interaction, thus causing functional imbalance of this complex in
      skeletal muscle that could contribute to the myopathy phenotype. In vivo, using
      bi-molecular fluorescent complementation, we show the specific binding of the two
      proteins inside the intact cell, in a unique interaction pattern between the two
      partners. This interaction is disrupted in the absence of the C-terminal
      calmodulin-like domain of alpha-actinin 2, which is altered in alpha-actinin 1.
      Moreover, the binding of GNE to alpha-actinin 2 prevents additional binding of
      alpha-actinin 1 but not vice versa. These results suggest that the interaction
      between GNE and alpha-actinin 1 and alpha-actinin 2 occur at different sites in
      the alpha-actinin molecules and that for alpha-actinin 2 the interaction site is
      located at the C-terminus of the protein.

PMID- 27023226
TI  - Astragaloside IV, a Natural PPARgamma Agonist, Reduces Abeta Production in
      Alzheimer's Disease Through Inhibition of BACE1.
AB  - A number of epidemiological studies have established a link between Alzheimer's
      disease (AD) and diabetes mellitus (DM). So, nuclear receptor peroxisome
      proliferator-activated receptor gamma (PPARgamma) plays an important role in the
      treatment of AD. However, current PPARgamma-targeting drugs such as
      thiazolidinediones (TZDs) are associated with undesirable side effects. We
      identified herbal extract with a small molecular, astragaloside IV (AS-IV), as a
      selective PPARgamma natural agonist in nervous cells by developing a PPAR-PPRE
      pathway regulatory system. Cultured SH-SY5Y cells transfected with pEGFP-N1-BACE1
      were treated with AS-IV for 24 h or AS-IV plus the PPAR-gamma antagonist GW9662
      in vitro. APP/PS1 mice were intragastrically treated with AS-IV or AS-IV plus the
      GW9662 every 48 h for 3 months. Immunofluorescence, western blotting, and real
      time PCR were used to examine the expression of PPARgamma and BACE1.
      Immunohistochemical staining was performed to analyze the distribution of Abeta
      plaques in the APP/PS1 mouse brain. The levels of Abeta were determined using
      ELISA kits. AS-IV was shown to be a PPARgamma agonist by establishing a high
      throughput screening model for PPARgamma agonists. The results showed that AS-IV
      treatment increased activity of PPARgamma and inhibited BACE1 in vitro. As a
      result, Abeta levels decreased significantly. GW9662, which is a PPARgamma
      antagonist, significantly blocked the beneficial role of AS-IV. In vivo, AS-IV
      treatment increased PPARgamma and BACE1 expression and reduced neuritic plaque
      formation and Abeta levels in the brains of APP/PS1 mice. These effects of AS-IV
      could be effectively inhibited by GW9662. These results indicate that AS-IV may
      be a natural PPARgamma agonist that suppressed activity of BACE1 and ultimately
      attenuates generation of Abeta. Therefore, AS-IV may be a promising agent for
      modulating Abeta-related pathology in AD.

PMID- 27023229
TI  - Lipids: From Chemical Structures, Biosynthesis, and Analyses to Industrial
      Applications.
AB  - Lipids are one of the major subcellular components, and play numerous essential
      functions. As well as their physiological roles, oils stored in biomass are
      useful commodities for a variety of biotechnological applications including food,
      chemical feedstocks, and fuel. Due to their agronomic as well as economic and
      societal importance, lipids have historically been subjected to intensive
      studies. Major current efforts are to increase the energy density of cell
      biomass, and/or create designer oils suitable for specific applications. This
      chapter covers some basic aspects of what one needs to know about lipids:
      definition, structure, function, metabolism and focus is also given on the
      development of modern lipid analytical tools and major current engineering
      approaches for biotechnological applications. This introductory chapter is
      intended to serve as a primer for all subsequent chapters in this book outlining
      current development in specific areas of lipids and their metabolism. 

PMID- 27023228
TI  - Ursodeoxycholic Acid Attenuates Acute Aortic Dissection Formation in Angiotensin
      II-Infused Apolipoprotein E-Deficient Mice Associated with Reduced ROS and
      Increased Nrf2 Levels.
AB  - BACKGROUND/AIMS: Acute aortic dissection (AAD) is characterized by excessive
      smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and
      inflammation. In response to certain stimulations, oxidative stress is activated
      and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic
      inflammation and degeneration, leading to AAD formation. This study aimed to
      clarify role of oxidative stress in the pathogenesis of AAD and whether the
      antioxidant ursodeoxycholic acid (UDCA) attenuates AAD formation. METHODS:
      Angiotensin II (Ang II) was infused in 8-months male ApoE-/- mice for one week to
      establish a model of AAD. UDCA (10 mg/kg/day) was administered via intragastric
      gavage for 3 consecutive days before AngII infusion and also during the AngII
      infusion for another consecutive 7 days. RESULTS: Ang II-infusion resulted in the
      incidence of AAD at a rate of 35% (13/37) and UDCA markedly reduced the incidence
      of AAD to 16% (6/37), accompanied with reduced maximal aortic diameter measured
      at the suprarenal region of the abdominal aorta. Additionally, UDCA pretreatment
      prevented Ang II induced generations of reactive oxygen species (ROS) and
      apoptosis of vascular smooth muscle cells (VSMCs) both in vivo and in. vitro
      Mechanistically, we found UDCA markedly increased Nrf2 expression in VSMCs and
      prevented Ang II induced expression of NADPH subunits (p47, p67 and gp91) in Nrf2
      dependent manner and rescued the activity of redox enzymes (Cu/Zn-SOD, Mn-SOD and
      CAT), thereby inhibiting apoptosis of VSMCs. CONCLUSION: These results
      demonstrate that UDCA prevented AAD formation by reducing apoptosis of VSMCs
      caused by oxidative stress in Nrf2 dependent manner and suggest that UDCA might
      have clinical potential to suppress AAD formation.

PMID- 27023227
TI  - Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its
      Association with Disease Progression and Disability.
AB  - Inflammation is the driving force for brain injury in patients with multiple
      sclerosis (MS). The objective of the present study is to delineate the serum
      cytokine profile in patients with progressive MS in a Southern Brazilian
      population compared with healthy controls and patients with relapsing-remitting
      MS (RRMS) and its associations with disease progression and disability. We
      included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls.
      The patients were evaluated using the Expanded Disability Status Scale (EDSS) and
      magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1beta,
      IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-10, IL
      4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL
      1beta, IL-6, TNF-alpha, IFN-gamma, IL-17, IL-4, and IL-10 levels were higher in
      progressive MS than in controls. Increased IL-1beta and IFN-gamma and decreased
      IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients
      with progressive MS with disease progression presented higher TNF-alpha, IFN
      gamma, and IL-10 levels than those without disease progression. Patients with
      progressive MS with disease progression showed a higher frequency of positive
      gadolinium-enhanced lesions in MRI; higher TNF-alpha, IFN-gamma, and IL-17
      levels; and decreased IL-12 levels compared with RRMS patients with progression.
      There was a significant inverse correlation between IL-10 levels and EDSS score
      in patients with progressive MS. The results underscore the complex cytokine
      network imbalance exhibited by progressive MS patients and show the important
      involvement of TNF-alpha, IFN-gamma, and IL-17 in the pathophysiology and
      progression of the disease. Moreover, serum IL-10 levels were inversely
      associated with disability in patients with progressive MS.

PMID- 27023230
TI  - Roles of Lipids in Photosynthesis.
AB  - Thylakoid membranes in cyanobacterial cells and chloroplasts of algae and higher
      plants are the sites of oxygenic photosynthesis. The lipid composition of the
      thylakoid membrane is unique and highly conserved among oxygenic photosynthetic
      organisms. Major lipids in thylakoid membranes are glycolipids,
      monogalactosyldiacylglycerol, digalactosyldiacylglycerol and
      sulfoquinovosyldiacylglycerol, and the phospholipid, phosphatidylglycerol. The
      identification of almost all genes involved in the biosynthesis of each lipid
      class over the past decade has allowed the generation and isolation of mutants of
      various photosynthetic organisms incapable of synthesizing specific lipids.
      Numerous studies using such mutants have revealed that these lipids play
      important roles not only in the formation of the lipid bilayers of thylakoid
      membranes but also in the folding and assembly of the protein subunits in
      photosynthetic complexes. In addition to the studies with the mutants, recent X
      ray crystallography studies of photosynthetic complexes in thylakoid membranes
      have also provided critical information on the association of lipids with
      photosynthetic complexes and their activities. In this chapter, we summarize our
      current understanding about the structural and functional involvement of
      thylakoid lipids in oxygenic photosynthesis. 

PMID- 27023231
TI  - DGDG and Glycolipids in Plants and Algae.
AB  - Photosynthetic organelles in plants and algae are characterized by the high
      abundance of glycolipids, including the galactolipids mono- and
      digalactosyldiacylglycerol (MGDG, DGDG) and the sulfolipid
      sulfoquinovosyldiacylglycerol (SQDG). Glycolipids are crucial to maintain an
      optimal efficiency of photosynthesis. During phosphate limitation, the amounts of
      DGDG and SQDG increase in the plastids of plants, and DGDG is exported to
      extraplastidial membranes to replace phospholipids. Algae often use betaine
      lipids as surrogate for phospholipids. Glucuronosyldiacylglycerol (GlcADG) is a
      further glycolipid that accumulates under phosphate deprived conditions. In
      contrast to plants, a number of eukaryotic algae contain very long chain
      polyunsaturated fatty acids of 20 or more carbon atoms in their glycolipids. The
      pathways and genes for galactolipid and sulfolipid synthesis are largely
      conserved between plants, Chlorophyta, Rhodophyta and algae with complex plastids
      derived from secondary or tertiary endosymbiosis. However, the relative
      contribution of the endoplasmic reticulum- and plastid-derived lipid pathways for
      glycolipid synthesis varies between plants and algae. The genes for glycolipid
      synthesis encode precursor proteins imported into the photosynthetic organelles.
      While most eukaryotic algae contain the plant-like galactolipid (MGD1, DGD1) and
      sulfolipid (SQD1, SQD2) synthases, the red alga Cyanidioschyzon harbors a
      cyanobacterium-type DGDG synthase (DgdA), and the amoeba Paulinella, derived from
      a more recent endosymbiosis event, contains cyanobacterium-type enzymes for MGDG
      and DGDG synthesis (MgdA, MgdE, DgdA). 

PMID- 27023232
TI  - Thylakoid Development and Galactolipid Synthesis in Cyanobacteria.
AB  - Cyanobacteria carry out oxygenic photosynthesis and share many features with
      chloroplasts, including thylakoid membranes, which are mainly composed of
      membrane lipids and protein complexes that mediate photosynthetic electron
      transport. Although the functions of the various thylakoid protein complexes have
      been well characterized, the details underlying the biogenesis of thylakoid
      membranes remain unclear. Galactolipids are the major constituents of the
      thylakoid membrane system, and all the genes involved in galactolipid
      biosynthesis were recently identified. In this chapter, I summarize recent
      advances in our understanding of the factors involved in thylakoid development,
      including regulatory proteins and enzymes that mediate lipid biosynthesis. 

PMID- 27023233
TI  - Role of Lipids in Chloroplast Biogenesis.
AB  - Chloroplasts are plant organelles that develop the thylakoid membrane inside to
      perform oxygenic photosynthesis. The biogenesis of the thylakoid membrane
      requires coordinated synthesis and assembly of proteins, pigments and many
      photosynthetic cofactors with membrane glycerolipids. The lipid bilayer of the
      thylakoid membrane mainly consists of four lipid classes;
      monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG),
      sulfoquinovosyldiacylglycerol (SQDG) and phosphatidylglycerol (PG), each of which
      has specific roles in biogenesis and maintenance of thylakoid membranes and
      photosynthesis. Galactolipids MGDG and DGDG constitute the bulk of membrane
      lipids in chloroplasts and are essential as major structural components of the
      thylakoid membrane. In addition to galactolipids, the thylakoid membrane requires
      a certain level of anionic lipids SQDG and PG for its function. Although SQDG and
      PG substitute for each other to maintain the amount of total anionic lipids in
      chloroplasts, PG has specific roles in photosynthesis that cannot be compensated
      by SQDG and galactolipids. In this chapter, we summarize roles of lipids in
      chloroplast functions with their biosynthetic pathways, which have been mainly
      established in Arabidopsis, and discuss an involvement of lipid biosynthesis in
      coordinated development of photosynthetic machinery during chloroplast
      biogenesis.

PMID- 27023234
TI  - Role of MGDG and Non-bilayer Lipid Phases in the Structure and Dynamics of
      Chloroplast Thylakoid Membranes.
AB  - In this chapter we focus our attention on the enigmatic structural and functional
      roles of the major, non-bilayer lipid monogalactosyl-diacylglycerol (MGDG) in the
      thylakoid membrane. We give an overview on the state of the art on the role of
      MGDG and non-bilayer lipid phases in the xanthophyll cycles in different
      organisms. We also discuss data on the roles of MGDG and other lipid molecules
      found in crystal structures of different photosynthetic protein complexes and in
      lipid-protein assemblies, as well as in the self-assembly of the multilamellar
      membrane system. Comparison and critical evaluation of different membrane models-
      that take into account and capitalize on the special properties of non-bilayer
      lipids and/or non-bilayer lipid phases, and thus to smaller or larger extents
      deviate from the 'standard' Singer-Nicolson model--will conclude this review.
      With this chapter the authors hope to further stimulate the discussion about,
      what we think, is perhaps the most exciting question of membrane biophysics: the
      why and wherefore of non-bilayer lipids and lipid phases in, or in association
      with, bilayer biological membranes.

PMID- 27023235
TI  - Chemical Genetics in Dissecting Membrane Glycerolipid Functions.
AB  - Chemical genetics has emerged as a powerful approach to dissect biological
      processes, based on the utilization of small molecules disturbing the function of
      specific target proteins. By analogy with classical genetics, 'reverse chemical
      genetics' refers to the utilization of drugs acting on a known target, enabling
      its functional characterization at the levels of the cells, tissues and
      organisms. Likewise, 'direct chemical genetics' refers to the utilization of a
      drug of unknown mode of action, but triggering a phenotype of interest. In that
      case, one has to identify the target(s) possibly blocked (or possibly activated)
      by the small molecule. This chapter illustrates both approaches, like the
      analysis of the elongation of fatty acids, the biosynthesis of
      galactoglycerolipids or the catabolism of phosphoglycerolipids by reverse
      chemical genetics or the study of the membrane glycerolipid remodeling triggered
      upon phosphate starvation, by direct chemical genetics. 

PMID- 27023236
TI  - Triacylglycerol Accumulation in Photosynthetic Cells in Plants and Algae.
AB  - Plant and algal oils are some of the most energy-dense renewable compounds
      provided by nature. Triacylglycerols (TAGs) are the major constituent of plant
      oils, which can be converted into fatty acid methyl esters commonly known as
      biodiesel. As one of the most efficient producers of TAGs, photosynthetic
      microalgae have attracted substantial interest for renewable fuel production.
      Currently, the big challenge of microalgae based TAGs for biofuels is their high
      cost compared to fossil fuels. A conundrum is that microalgae accumulate large
      amounts of TAGs only during stress conditions such as nutrient deprivation and
      temperature stress, which inevitably will inhibit growth. Thus, a better
      understanding of why and how microalgae induce TAG biosynthesis under stress
      conditions would allow the development of engineered microalgae with increased
      TAG production during conditions optimal for growth. Land plants also synthesize
      TAGs during stresses and we will compare new findings on environmental stress
      induced TAG accumulation in plants and microalgae especially in the well
      characterized model alga Chlamydomonas reinhardtii and a biotechnologically
      relevant genus Nannochloropsis. 

PMID- 27023237
TI  - Cellular Organization of Triacylglycerol Biosynthesis in Microalgae.
AB  - Eukaryotic cells are characterized by compartmentalization and specialization of
      metabolism within membrane-bound organelles. Nevertheless, many fundamental
      processes extend across multiple subcellular compartments. Here, we describe and
      assess the pathways and cellular organization of triacylglycerol biosynthesis in
      microalgae. In particular, we emphases the dynamic interplay among the
      endoplasmic reticulum, lipid droplets and chloroplasts in acyl remodeling and
      triacylglycerol accumulation under nitrogen starvation in the model alga
      Chlamydomonas reinhardtii. 

PMID- 27023238
TI  - High-Throughput Genetics Strategies for Identifying New Components of Lipid
      Metabolism in the Green Alga Chlamydomonas reinhardtii.
AB  - Microalgal lipid metabolism is of broad interest because microalgae accumulate
      large amounts of triacylglycerols (TAGs) that can be used for biodiesel
      production (Durrett et al Plant J 54(4):593-607, 2008; Hu et al Plant J 54(4):621
      639, 2008). Additionally, green algae are close relatives of land plants and
      serve as models to understand conserved lipid metabolism pathways in the green
      lineage. The green alga Chlamydomonas reinhardtii (Chlamydomonas hereafter) is a
      powerful model organism for understanding algal lipid metabolism. Various methods
      have been used to screen Chlamydomonas mutants for lipid amount or composition,
      and for identification of the mutated loci in mutants of interest. In this
      chapter, we summarize the advantages and caveats for each of these methods with a
      focus on screens for mutants with perturbed TAG content. We also discuss
      technical opportunities and new tools that are becoming available for screens of
      mutants altered in TAG content or perturbed in other processes in Chlamydomonas. 

PMID- 27023239
TI  - Plant Sphingolipid Metabolism and Function.
AB  - Sphingolipids, a once overlooked class of lipids in plants, are now recognized as
      abundant and essential components of plasma membrane and other endomembranes of
      plant cells. In addition to providing structural integrity to plant membranes,
      sphingolipids contribute to Golgi trafficking and protein organizational domains
      in the plasma membrane. Sphingolipid metabolites have also been linked to the
      regulation of cellular processes, including programmed cell death. Advances in
      mass spectrometry-based sphingolipid profiling and analyses of Arabidopsis
      mutants have enabled fundamental discoveries in sphingolipid structural
      diversity, metabolism, and function that are reviewed here. These discoveries are
      laying the groundwork for the tailoring of sphingolipid biosynthesis and
      catabolism for improved tolerance of plants to biotic and abiotic stresses. 

PMID- 27023240
TI  - Plant Surface Lipids and Epidermis Development.
AB  - The epidermis has a strategic position at the interface between the plant and the
      environment. In order to control exchanges with the environment as well as to
      protect the plant from external threats, the epidermis synthesises and secretes
      surface lipids to form a continuous, transparent and hydrophobic layer known as
      the cuticle. Cuticle formation is a strictly epidermal property in plants and all
      aerial epidermal cells produce some sort of cuticle on their surface. Conversely,
      all cuticularized plant surfaces are of epidermal origin. This seemingly anodyne
      observation has surprisingly profound implications in terms of understanding the
      function of the plant cuticle, since it underlies in part, the difficultly of
      functionally separating epidermal cell fate specification from cuticle
      biogenesis. 

PMID- 27023241
TI  - Role of Lipid Metabolism in Plant Pollen Exine Development.
AB  - Pollen plays important roles in the life cycle of angiosperms plants. It acts as
      not only a biological protector of male sperms but also a communicator between
      the male and the female reproductive organs, facilitating pollination and
      fertilization. Pollen is produced within the anther, and covered by the
      specialized outer envelope, pollen wall. Although the morphology of pollen varies
      among different plant species, the pollen wall is mainly comprised of three
      layers: the pollen coat, the outer exine layer, and the inner intine layer.
      Except the intine layer, the other two layers are basically of lipidic nature.
      Particularly, the outer pollen wall layer, the exine, is a highly resistant
      biopolymer of phenylpropanoid and lipidic monomers covalently coupled by ether
      and ester linkages. The precise molecular mechanisms underlying pollen coat
      formation and exine patterning remain largely elusive. Herein, we summarize the
      current genetic, phenotypic and biochemical studies regarding to the pollen exine
      development and underlying molecular regulatory mechanisms mainly obtained from
      monocot rice (Oryza sativa) and dicot Arabidopsis thaliana, aiming to extend our
      understandings of plant male reproductive biology. Genes, enzymes/proteins and
      regulatory factors that appear to play conserved and diversified roles in lipid
      biosynthesis, transportation and modification during pollen exine formation, were
      highlighted. 

PMID- 27023242
TI  - Long-Distance Lipid Signaling and its Role in Plant Development and Stress
      Response.
AB  - Lipids are important signaling compounds in plants. They can range from small
      lipophilic molecules like the dicarboxylic acid Azelaic acid to complex
      phosphoglycerolipids and regulate plant development as well as the response to
      biotic and abiotic stress. While their intracellular function is well described,
      several lipophilic signals are known to be found in the plant phloem and can,
      thus, also play a role in long-distance signaling. Mostly, they play a role in
      the pathogen response and systemic acquired resistance. This is particularly true
      for oxylipins, dehydroabietinal, and azelaic acid. However, several phospholipids
      have now been described in phloem exudates. Their intracellular function as well
      as implications and a model for long-distance signaling are discussed in this
      chapter. 

PMID- 27023243
TI  - Acyl-CoA-Binding Proteins (ACBPs) in Plant Development.
AB  - Acyl-CoA-binding proteins (ACBPs) play a pivotal role in fatty acid metabolism
      because they can transport medium- and long-chain acyl-CoA esters. In eukaryotic
      cells, ACBPs are involved in intracellular trafficking of acyl-CoA esters and
      formation of a cytosolic acyl-CoA pool. In addition to these ubiquitous
      functions, more specific non-redundant roles of plant ACBP subclasses are
      implicated by the existence of multigene families with variable molecular masses,
      ligand specificities, functional domains (e.g. protein-protein interaction
      domains), subcellular locations and gene expression patterns. In this chapter,
      recent progress in the characterization of ACBPs from the model dicot plant,
      Arabidopsis thaliana, and the model monocot, Oryza sativa, and their emerging
      roles in plant growth and development are discussed. The functional significance
      of respective members of the plant ACBP families in various developmental and
      physiological processes such as seed development and germination, stem cuticle
      formation, pollen development, leaf senescence, peroxisomal fatty acid beta
      oxidation and phloem-mediated lipid transport is highlighted. 

PMID- 27023244
TI  - The Rise and Fall of Jasmonate Biological Activities.
AB  - Jasmonates (JAs) constitute a major class of plant regulators that coordinate
      responses to biotic and abiotic threats and important aspects of plant
      development. The core biosynthetic pathway converts linolenic acid released from
      plastid membrane lipids to the cyclopentenone cis-oxo-phytodienoic acid (OPDA)
      that is further reduced and shortened to jasmonic acid (JA) in peroxisomes.
      Abundant pools of OPDA esterified to plastid lipids also occur upon stress,
      mainly in the Arabidopsis genus. Long thought to be the bioactive hormone, JA
      only gains its pleiotropic hormonal properties upon conjugation into jasmonoyl
      isoleucine (JA-Ile). The signaling pathway triggered when JA-Ile promotes the
      assembly of COI1-JAZ (Coronatine Insensitive 1-JAsmonate Zim domain) co-receptor
      complexes has been the focus of most recent research in the jasmonate field. In
      parallel, OPDA and several other JA derivatives are recognized for their separate
      activities and contribute to the diversity of jasmonate action in plant
      physiology. We summarize in this chapter the properties of different bioactive
      JAs and review elements known for their perception and signal transduction. Much
      progress has also been gained on the enzymatic processes governing JA-Ile
      removal. Two JA-Ile catabolic pathways, operating through omega-oxidation
      (cytochromes P450) or conjugate cleavage (amido hydrolases) shape signal dynamics
      to allow optimal control on defense. JA-Ile turnover not only participates in
      signal attenuation, but also impact the homeostasis of the entire JA metabolic
      pathway. 

PMID- 27023245
TI  - Green Leaf Volatiles in Plant Signaling and Response.
AB  - Most 'green' plants form green leaf volatiles (GLVs). GLVs are a familiar plant
      secondary metabolite, but knowledge of their physiological and ecological
      functions is limited. GLV formation is tightly suppressed when plant tissues are
      intact, but upon mechanical wounding, herbivore attack, or abiotic stresses, GLVs
      are formed rapidly, within seconds or minutes. Thus, this may be an important
      system for defense responses, allowing plants to protect themselves from damage
      as soon as possible. Because GLV formation in the natural environment is roughly
      related to the degree of stress in the plant life, sensing the amount of GLVs in
      the atmosphere might allow plants to recognize their surroundings. Because some
      plants respond to GLVs, they may communicate with GLVs. GLVs that contain
      alpha,beta-unsaturated carbonyl groups might activate signaling systems regulated
      under the redox state of plant cells. Plasma membranes would also be targets of
      interactions with GLVs. Additionally, the metabolism of GLVs in plant cells after
      absorption from the atmosphere could also be classified as a plant-plant
      interaction. 

PMID- 27023246
TI  - Omics in Chlamydomonas for Biofuel Production.
AB  - In response to demands for sustainable domestic fuel sources, research into
      biofuels has become increasingly important. Many challenges face biofuels in
      their effort to replace petroleum fuels, but rational strain engineering of algae
      and photosynthetic organisms offers a great deal of promise. For decades,
      mutations and stress responses in photosynthetic microbiota were seen to result
      in production of exciting high-energy fuel molecules, giving hope but minor
      capability for design. However, '-omics' techniques for visualizing entire cell
      processing has clarified biosynthesis and regulatory networks. Investigation into
      the promising production behaviors of the model organism C. reinhardtii and its
      mutants with these powerful techniques has improved predictability and
      understanding of the diverse, complex interactions within photosynthetic
      organisms. This new equipment has created an exciting new frontier for high
      throughput, predictable engineering of photosynthetically produced carbon-neutral
      biofuels. 

PMID- 27023247
TI  - Microalgae as a Source for VLC-PUFA Production.
AB  - Microalgae present a huge and still insufficiently tapped resource of very long
      chain omega-3 and omega-6 polyunsaturated fatty acids (VLC-PUFA) for human
      nutrition and medicinal applications. This chapter describes the diversity of
      unicellular eukaryotic microalgae in respect to VLC-PUFA biosynthesis. Then, we
      outline the major biosynthetic pathways mediating the formation of VLC-PUFA by
      sequential desaturation and elongation of C18-PUFA acyl groups. We address the
      aspects of spatial localization of those pathways and elaborate on the role for
      VLC-PUFA in microalgal cells. Recent progress in microalgal genetic
      transformation and molecular engineering has opened the way to increased
      production efficiencies for VLC-PUFA. The perspectives of photobiotechnology and
      metabolic engineering of microalgae for altered or enhanced VLC-PUFA production
      are also discussed. 

PMID- 27023248
TI  - Understanding Sugar Catabolism in Unicellular Cyanobacteria Toward the
      Application in Biofuel and Biomaterial Production.
AB  - Synechocystis sp. PCC 6803 is a model species of the cyanobacteria that undergo
      oxygenic photosynthesis, and has garnered much attention for its potential
      biotechnological applications. The regulatory mechanism of sugar metabolism in
      this cyanobacterium has been intensively studied and recent omics approaches have
      revealed the changes in transcripts, proteins, and metabolites of sugar
      catabolism under different light and nutrient conditions. Several transcriptional
      regulators that control the gene expression of enzymes related to sugar
      catabolism have been identified in the past 10 years, including a sigma factor,
      transcription factors, and histidine kinases. The modification of these genes can
      lead to alterations in the primary metabolism as well as the levels of high-value
      products such as bioplastics and hydrogen. This review summarizes recent studies
      on sugar catabolism in Synechocystis sp. PCC 6803, emphasizing the importance of
      elucidating the molecular mechanisms of cyanobacterial metabolism for
      biotechnological applications. 

PMID- 27023249
TI  - ZEISS AngioplexTM Spectral Domain Optical Coherence Tomography Angiography:
      Technical Aspects.
AB  - ZEISS AngioplexTM optical coherence tomography (OCT) angiography generates high
      resolution three-dimensional maps of the retinal and choroidal microvasculature
      while retaining all of the capabilities of the existing CIRRUSTM HD-OCT Model
      5000 instrument. AngioplexTM OCT angiographic imaging on the CIRRUSTM HD-OCT
      platform was made possible by increasing the scanning rate to 68,000 A-scans per
      second and introducing improved tracking software known as FastTracTM retinal
      tracking technology. The generation of en face microvascular flow images with
      AngioplexTM OCT uses an algorithm known as OCT microangiography-complex, which
      incorporates differences in both the phase and intensity information contained
      within sequential B-scans performed at the same position. Current scanning
      patterns for en face angiographic visualization include a 3 * 3 and a 6 * 6 mm
      scan pattern on the retina. A volumetric dataset showing erythrocyte flow
      information can then be displayed as a color-coded retinal depth map in which the
      microvasculature of the superficial, deep, and avascular layers of the retina are
      displayed together with the colors red, representing the superficial
      microvasculature; green, representing the deep retinal vasculature; and blue,
      representing any vessels present in the normally avascular outer retina. Each
      retinal layer can be viewed separately, and the microvascular layers representing
      the choriocapillaris and the remaining choroid can be viewed separately as well.
      In addition, readjusting the contours of the slabs to target different layers of
      interest can generate custom en face flow images. Moreover, each en face flow
      image is accompanied by an en face intensity image to help with the
      interpretation of the flow results. Current clinical experience with this
      technology would suggest that OCT angiography should replace fluorescein
      angiography for retinovascular diseases involving any area of the retina that can
      be currently scanned with the CIRRUSTM HD-OCT instrument and may replace
      fluorescein angiography and indocyanine green angiography for some choroidal
      vascular diseases. 

PMID- 27023250
TI  - Unpredictable environments lead to the evolution of parental neglect in birds.
AB  - A nest of begging chicks invites an intuitive explanation: needy chicks want to
      be fed and parents want to feed them. Surprisingly, however, in a quarter of
      species studied, parents ignore begging chicks. Furthermore, parents in some
      species even neglect smaller chicks that beg more, and preferentially feed the
      biggest chicks that beg less. This extreme variation across species, which
      contradicts predictions from theory, represents a major outstanding problem for
      the study of animal signalling. We analyse parent-offspring communication across
      143 bird species, and show that this variation correlates with ecological
      differences. In predictable and good environments, chicks in worse condition beg
      more, and parents preferentially feed those chicks. In unpredictable and poor
      environments, parents pay less attention to begging, and instead rely on size
      cues or structural signals of quality. Overall, these results show how ecological
      variation can lead to different signalling systems being evolutionarily stable in
      different species. 

PMID- 27023251
TI  - Antithrombotic and Antioxidant Activity of Amaranth Hydrolysate Obtained by
      Activation of an Endogenous Protease.
AB  - Ingestion of diets with antithrombotic and antioxidant components offer a
      convenient and effective way to prevent and reduce the incidence of
      cardiovascular diseases. The aim of the present work was to obtain an amaranth
      hydrolysate by the activation of an endogenous aspartic protease, to establish
      adequate experimental conditions, and to evaluate its antithrombotic and
      antioxidant activity in order to assess its potential application as an
      ingredient in functional foods. The results obtained not only confirmed the
      presence of an endogenous protease in the amaranth isolate, but also allowed us
      to select an adequate incubation conditions (pH 2, 40  degrees C, 16 h). The
      hydrolysate obtained (degree of hydrolysis 5.3 +/- 0.4 %) showed potential
      antithrombotic activity (IC50 = 5.9 +/- 0.1 mg soluble protein/mL) and had more
      antioxidant activity than the isolate, indicating that the activation of the
      protease released bioactive peptides from amaranth proteins. Decreasing the pH is
      a simple and cheap process and is another way to obtain potential functional
      ingredients with bioactive compounds. 

PMID- 27023252
TI  - Stromal Palladin Expression Is an Independent Prognostic Factor in Pancreatic
      Ductal Adenocarcinoma.
AB  - It has been clear that cancer-associated fibroblasts (CAFs) in the tumor
      microenvironment play an important role in pancreatic ductal adenocarcinoma
      (PDAC) progression. However, how CAFs relate to the patients' prognosis and the
      effects of chemoradiation therapy (CRT) has not been fully investigated. Tissue
      microarrays (TMAs) representing 167 resected PDACs without preoperative treatment
      were used for immunohistochemical studies (IHC) of palladin, alpha-smooth muscle
      actin (SMA), and podoplanin. Correlations between the expression levels of these
      markers and clinicopathological findings were analyzed statistically. Whole
      sections of surgical specimens from PDACs with and without preoperative CRT,
      designated as the chemotherapy-first group (CF, n = 19) and the surgery-first
      group (SF, n = 21), respectively, were also analyzed by IHC. In TMAs, the disease
      specific survival rate (DSS) at 5 years for all 167 cases was 23.1%. Seventy
      cases (41.9%) were positive for palladin and had significantly lower DSS (p =
      0.0430). alpha-SMA and podoplanin were positive in 167 cases (100%) and 131 cases
      (78.4%), respectively, and they were not significantly associated with DSS. On
      multivariable analysis, palladin expression was an independent poor prognostic
      factor (p = 0.0243, risk ratio 1.60). In the whole section study, palladin
      positivity was significantly lower (p = 0.0037) in the CF group (5/19) with a
      significantly better DSS (p = 0.0144) than in the SF group (16/22), suggesting
      that stromal palladin expression is a surrogate indicator of the treatment effect
      after chemoradiation therapy. 

PMID- 27023253
TI  - A Quantitative Glycomics and Proteomics Combined Purification Strategy.
AB  - There is a growing desire in the biological and clinical sciences to integrate
      and correlate multiple classes of biomolecules to unravel biology, define
      pathways, improve treatment, understand disease, and aid biomarker discovery. N
      linked glycosylation is one of the most important and robust post-translational
      modifications on proteins and regulates critical cell functions such as
      signaling, adhesion, and enzymatic function. Analytical techniques to purify and
      analyze N-glycans have remained relatively static over the last decade. While
      accurate and effective, they commonly require significant expertise and
      resources. Though some high-throughput purification schemes have been developed,
      they have yet to find widespread adoption and often rely on the enrichment of
      glycopeptides. One promising method, developed by Thomas-Oates et al., filter
      aided N-glycan separation (FANGS), was qualitatively demonstrated on tissues.
      Herein, we adapted FANGS to plasma and coupled it to the individuality
      normalization when labeling with glycan hydrazide tags strategy in order to
      achieve accurate relative quantification by liquid chromatography mass
      spectrometry and enhanced electrospray ionization. Furthermore, we designed new
      functionality to the protocol by achieving tandem, shotgun proteomics and
      glycosylation site analysis on hen plasma. We showed that N-glycans purified on
      filter and derivatized by hydrophobic hydrazide tags were comparable in terms of
      abundance and class to those by solid phase extraction (SPE); the latter is
      considered a gold standard in the field. Importantly, the variability in the two
      protocols was not statistically different. Proteomic data that was collected in
      line with glycomic data had the same depth compared to a standard trypsin digest.
      Peptide deamidation is minimized in the protocol, limiting non-specific
      deamidation detected at glycosylation motifs. This allowed for direct
      glycosylation site analysis, though the protocol can accommodate (18)O site
      labeling as well. Overall, we demonstrated a new in-line high-throughput,
      unbiased, filter based protocol for quantitative glycomics and proteomics
      analysis. 

PMID- 27023254
TI  - Fluorescence Detection of H5N1 Virus Gene Sequences Based on Optical Tweezers
      with Two-Photon Excitation Using a Single Near Infrared Nanosecond Pulse Laser.
AB  - We present an analytical platform by combining near-infrared optical tweezers
      with two-photon excitation for fluorescence detection of H5N1 virus gene
      sequences. A heterogeneous enrichment strategy, which involved polystyrene (PS)
      microsphere and quantum dots (QDs), was adopted. The final hybrid-conjugate
      microspheres were prepared by a facile one-step hybridization procedure by using
      PS microspheres capturing target DNA and QDs tagging, respectively. Quantitative
      detection was achieved by the optical tweezers setup with a low-cost 1064 nm
      nanosecond pulse laser for both optical trapping and two-photon excitation for
      the same hybrid-conjugate microsphere. The detection limits for both
      neuraminidase (NA) gene sequences and hemagglutinin (HA) gene sequences are 16-19
      pM with good selectivity for one-base mismatch, which is approximately 1 order of
      magnitude lower than the most existing fluorescence-based analysis method.
      Besides, because of the fact that only signal from the trapped particle is
      detected upon two-photon excitation, this approach showed extremely low
      background in fluorescence detection and was successfully applied to directly
      detect target DNA in human whole serum without any separation steps and the
      corresponding results are very close to that in buffer solution, indicating the
      strong anti-interference ability of this method. Therefore, it can be expected to
      be an emerging alternative for straightforward detecting target species in
      complex samples with a simple procedure and high-throughput. 

PMID- 27023255
TI  - ent-Labdane Diterpenoids from the Aerial Parts of Eupatorium obtusissmum.
AB  - Six new ent-labdane diterpenoids, uasdlabdanes A-F (1-6), were isolated from the
      aerial parts of Eupatorium obtusissmum. The new structures were elucidated
      through spectroscopic and spectrometric data analyses. The absolute
      configurations of compounds 1 and 2 were established by X-ray crystallography,
      and those of 3-6, by comparison of experimental and calculated electronic
      circular dichroism spectra. The antiproliferative activity of the compounds was
      studied in a panel of six representative human solid tumor cell lines and showed
      GI50 values ranging from 19 to >100 MUM. 

PMID- 27023256
TI  - Differentiation of Atrial Cardiomyocytes from Pluripotent Stem Cells Using the
      BMP Antagonist Grem2.
AB  - Protocols for generating populations of cardiomyocytes from pluripotent stem
      cells have been developed, but these generally yield cells of mixed phenotypes.
      Researchers interested in pursuing studies involving specific myocyte subtypes
      require a more directed differentiation approach. By treating mouse embryonic
      stem (ES) cells with Grem2, a secreted BMP antagonist that is necessary for
      atrial chamber formation in vivo, a large number of cardiac cells with an atrial
      phenotype can be generated. Use of the engineered Myh6-DSRed-Nuc pluripotent stem
      cell line allows for identification, selection, and purification of
      cardiomyocytes. In this protocol embryoid bodies are generated from Myh6-DSRed
      Nuc cells using the hanging drop method and kept in suspension until
      differentiation day 4 (d4). At d4 cells are treated with Grem2 and plated onto
      gelatin coated plates. Between d8-d10 large contracting areas are observed in the
      cultures and continue to expand and mature through d14. Molecular, histological
      and electrophysiogical analyses indicate cells in Grem2-treated cells acquire
      atrial-like characteristics providing an in vitro model to study the biology of
      atrial cardiomyocytes and their response to various pharmacological agents. 

PMID- 27023257
TI  - Determination of the median effective dose (ED50) of spinal plain ropivacaine for
      motor block in adults.
AB  - BACKGROUND: The median effective dose (ED50) for motor blockade of spinal plain
      bupivacaine in adults was previously reported; however, that of ropivacaine is
      unknown. This study aimed to determine the ED50 for motor blockade of spinal
      plain ropivacaine in adults, evaluating the effect of age on this parameter.
      METHODS: 133 patients in need of combined spinal and epidural anesthesia were
      enrolled in this sequential allocation study. They were divided into 6 groups
      according to age: 20-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years. Using the
      up-and-down method of Dixon, the ropivacaine dose was varied according to the
      preceding patient's reaction. The modified Bromage and hip motor function score
      was used to evaluate the degree of motor block after administration of
      ropivacaine. ED50 values were estimated by the method of Dixon and Massey. Other
      indexes, including the onset of motor block, the analgesia level, and the
      duration of motor block were also assessed. RESULTS: the ED50 for motor block of
      intrathecal ropivacaine was 20.96 mg (95 % CI: 19.83-22.16 mg) in 20-30, 19.05 mg
      (95 % CI: 18.43-19.70 mg) in 31-40, 17.91 mg (95 % CI: 17.10-18.76 mg) in 41-50,
      17.91 mg (95 % CI: 16.49-19.44 mg) in 51-60, 16.11 mg (95 % CI: 14.50-17.90 mg)
      in 61-70, and 15.75 mg (95 % CI: 13.98-17.73 mg) in 71-80 year-old patients.
      Maximum cephalic analgesic effects were obtained at the L4-T6 and L4-T2 levels,
      at 5 and 10 min, respectively, after intrathecal administration of ropivacaine in
      all groups. CONCLUSION: the ED50 for motor block in spinal plain ropivacaine
      decreases with advancing age, indicating that age has an influence on the potency
      of spinal ropivacaine.

PMID- 27023258
TI  - Theoretical versus Ex Vivo Assessment of Radiation Damage Repair: An
      Investigation in Normal Breast Tissue.
AB  - In vivo validation of models of DNA damage repair will enable their use for
      optimizing clinical radiotherapy. In this study, a theoretical assessment was
      made of DNA double-strand break (DSB) induction in normal breast tissue after
      intraoperative radiation therapy (IORT), which is now an accepted form of
      adjuvant radiotherapy for selected patients with early breast cancer. DSB rates
      and relative biological effectiveness (RBE) were calculated as a function of
      dose, radiation quality and dose rate, each varying based on the applicator size
      used during IORT. The spectra of primary electrons in breast tissue adjacent to
      each applicator were calculated using measured X-ray spectra and Monte Carlo
      methods, and were used to inform a Monte Carlo damage simulation code. In the
      absence of repair, asymptotic RBE values (relative to (60)Co) were approximately
      1.5. Beam-quality changes led to only minor variations in RBE among applicators,
      though differences in dose rate and overall dose delivery time led to larger
      variations and a rapid decrease in RBE. An experimental assessment of DSB
      induction was performed ex vivo using pre- and postirradiation tissue samples
      from patients receiving breast intraoperative radiation therapy. Relative DSB
      rates were assessed via gamma-H2AX immunohistochemistry using proportional
      staining. Maximum-likelihood parameter estimation yielded a DSB repair halftime
      of 25.9 min (95% CI, 21.5-30.4 min), although the resulting model was not
      statistically distinguishable from one where there was no change in DSB yield
      among patients. Although the model yielded an in vivo repair halftime of the
      order of previous estimates for in vitro repair halftimes, we cannot conclude
      that it is valid in this context. This study highlights some of the uncertainties
      inherent in population analysis of ex vivo samples, and of the quantitative
      limitations of immunohistochemistry for assessment of DSB repair. 

PMID- 27023259
TI  - X Irradiation Induces Acute Cognitive Decline via Transient Synaptic Dysfunction.
AB  - Cranial X irradiation can severely impair higher brain function, resulting in
      neurocognitive deficits. Radiation-induced brain injury is characterized by
      acute, early and late delayed changes, and morbidity is evident more than 6
      months after irradiation. While the acute effects of radiation exposure on the
      brain are known, the underlying mechanisms remain unclear. In this study, we
      examined the acute effect of X radiation on synaptic function using behavioral
      analysis and immunohistochemistry. We found that 10 Gy whole-brain irradiation
      immediately after conditioning (within 30 min) impaired the formation of fear
      memory, whereas irradiation 24 h prior to conditioning did not. To investigate
      the mechanisms underlying these behavioral changes, we irradiated one hemisphere
      of the brain and analyzed synaptic function and adult neurogenesis
      immunohistochemically. We focused on drebrin, whose loss from dendritic spines is
      a surrogate marker of synaptopathy. The intensity of drebrin immunoreactivity
      started to decrease in the irradiated hemisphere 2 h after exposure. The
      immunostaining intensity recovered to preirradiation levels by 24 h, indicating
      that X radiation induced transient synaptic dysfunction. Interestingly, the
      number of newly generated neurons was not changed at 2 h postirradiation, whereas
      it was significantly decreased at 8 and 24 h postirradiation. Because irradiation
      24 h prior to conditioning had no effect on fear memory, our findings suggest
      that radiation-induced death of newly-generated neurons does not substantially
      impact fear memory formation. The radiation-induced synaptic dysfunction likely
      caused a transient memory deficit during the critical period for fear memory
      formation (approximately 1-3 h after conditioning), which coincides with a change
      in drebrin immunostaining in the hippocampus, a structure critical for fear
      memory formation.

PMID- 27023260
TI  - Radioadaptive Response for Reproductive Cell Death Demonstrated in In Vivo Tissue
      Model of Caenorhabditis elegans.
AB  - Reproductive cell death (RCD) occurs after one or more cell divisions resulting
      from an insult such as radiation exposure or other treatments with carcinogens or
      mutagens. The radioadaptive response for RCD is usually investigated by in vitro
      or in vivo clonogenic assay. To date, this has not been demonstrated in the
      vulval tissue in Caenorhabditis elegans ( C. elegans ), which is a well
      established in vivo model for radiation-induced RCD. In this study to determine
      whether radioadaptive response occurs in the vulval tissue model of C. elegans ,
      early larval worms were gamma irradiated with lower adaptive doses, followed by
      higher challenge doses. The ratio of protruding vulva was used to assess the RCD
      of vulval cells. The results of this study showed that the radioadaptive response
      for RCD in this vulval tissue model could be well induced by dose combinations of
      5 + 75 Gy and 5 + 100 Gy at the time point of 14-16 h in worm development. In
      addition, the time course analysis indicated that radioresistance in vulval cells
      developed within 1.75 h after an adaptive dose and persisted for only a short
      period of time (2-4 h). DNA damage checkpoint and non-homologous end joining were
      involved in the radioadaptive response, exhibiting induction of protruding vulva
      in worms deficient in these two pathways similar to their controls.
      Interestingly, the DNA damage checkpoint was not active in the somatic vulval
      cells, and it was therefore suggested that the DNA damage checkpoint might
      mediate the radioadaptive response in a cell nonautonomous manner. Here, we show
      evidence of the occurrence of a radioadaptive response for RCD in the vulval
      tissue model of C. elegans . This finding provides a potential opportunity to
      gain further insight into the underlying mechanisms of the radioadaptive response
      for RCD, in view of the abundant genetic resources of C. elegans .

PMID- 27023261
TI  - A Comparison of Kinetic Photon Cell Survival Models.

PMID- 27023262
TI  - Circulating IL-18 Binding Protein (IL-18BP) and IL-18 as Dual Biomarkers of Total
      Body Irradiation in Mice.
AB  - We have previously reported that circulating interleukin-18 (IL-18) can be used
      as a radiation biomarker in mice, minipigs and nonhuman primates. In this study,
      we further determined the serum levels of IL-18 binding protein (IL-18BP), a
      natural endogenous antagonist of IL-18, in CD2F1 mice 1-13 days after total-body
      gamma irradiation (TBI) with different doses (5-10 Gy). We compared the changes
      in blood lymphocyte, neutrophil and platelet counts as well as the activation of
      the proapoptotic executioner caspase-3 and caspase-7, and the expression of the
      inflammatory factor cyclooxygenase 2 (COX-2) in spleen cells, with the changes of
      IL-18BP and IL-18 in mouse serum. We also evaluated the significance, sensitivity
      and specificity of alterations in radiation-induced IL-18BP. IL-18 increased from
      day 1-13 after TBI in a dose-dependent manner that was paralleled with an
      increase in IL-18 receptor alpha (IL-18Ralpha) in irradiated mouse spleen cells.
      IL-18BP rapidly increased (25-63 fold) in mouse serum on day 1 after different
      doses of TBI. However, it returned to baseline within 3 days after 5-7 Gy doses
      and within 7 days after 8 Gy dose, and was unaltered thereafter. In contrast,
      high doses of radiation (9 and 10 Gy) significantly sustained a higher level of
      IL-18BP in mouse serum and later induced a second phase of increase in IL-18BP on
      day 9-13 after irradiation, which coincided with the onset of animal mortality.
      Consistent with this observation, highly activated caspase-3 and -7 in 8-10 Gy
      irradiated mouse spleen cells exhibited reduced or no activity 24 h after 5 Gy,
      although radiation induced an inflammatory response, as shown by COX-2 expression
      in all irradiated cells. Our data suggest that the radiation-induced differential
      elevation of IL-18 and IL-18BP in animal serum is a dynamic and discriminative
      indicator of the severity of injury after exposure to ionizing radiation. These
      findings support the inclusion of the dual biomarkers IL-18BP and IL-18 in the
      development of a multifactorial strategy for radiation dose and injury
      assessment.

PMID- 27023264
TI  - A Prospective Study of Serotonin and Norepinephrine Transporter Genes and the
      Response to Desvenlafaxine Over 8 Weeks in Major Depressive Disorder.
AB  - No studies to date have evaluated SLC6A2 and SLC6A4 genetic polymorphisms
      influencing antidepressant response to desvenlafaxine. We conducted an 8-week,
      open-label, prospective pilot study in 35 patients with major depressive disorder
      to assess the effects of genetic variations in SLC6A2 and SLC6A4 on both efficacy
      and side effect profile of desvenlafaxine. Results revealed that homozygotes for
      the SLC6A4 HTTLPR S allele showed a 33% HDRS reduction compared to a 58%
      reduction for L allele carriers (p=0.037). No results survived adjustments for
      covariates or multiple comparisons. While these results need to be interpreted
      cautiously, they provide preliminary support for the SLC6A4 HTTLPR polymorphism
      as potential modifier of desvenlafaxine efficacy.

PMID- 27023263
TI  - The Risk of Cataract among Survivors of Childhood and Adolescent Cancer: A Report
      from the Childhood Cancer Survivor Study.
AB  - With therapeutic successes and improved survival after a cancer diagnosis in
      childhood, increasing numbers of cancer survivors are at risk of subsequent
      treatment-related morbidities, including cataracts. While it is well known that
      the lens of the eye is one of the most radiosensitive tissues in the human body,
      the risks associated with radiation doses less than 2 Gy are less understood, as
      are the long- and short-term cataract risks from exposure to ionizing radiation
      at a young age. In this study, we followed 13,902 five-year survivors of
      childhood cancer in the Childhood Cancer Survivor Study cohort an average of 21.4
      years from the date of first cancer diagnosis. For patients receiving
      radiotherapy, lens dose (mean: 2.2 Gy; range: 0-66 Gy) was estimated based on
      radiotherapy records. We used unconditional multivariable logistic regression
      models to evaluate prevalence of self-reported cataract in relationship to
      cumulative radiation dose both at five years after the initial cancer diagnosis
      and at the end of follow-up. We modeled the radiation effect in terms of the
      excess odds ratio (EOR) per Gy. We also analyzed cataract incidence starting from
      five years after initial cancer diagnosis to the end of follow-up using Cox
      regression. A total of 483 (3.5%) cataract cases were identified, including 200
      (1.4%) diagnosed during the first five years of follow-up. In a multivariable
      logistic regression model, cataract prevalence at the end of follow-up was
      positively associated with lens dose in a manner consistent with a linear dose
      response relationship (EOR per Gy = 0.92; 95% CI: 0.65-1.20). The odds ratio for
      doses between 0.5 and 1.5 Gy was elevated significantly relative to doses <0.5 Gy
      (OR = 2.2; 95% CI: 1.3-3.7). The results from this study indicate a strong
      association between ocular exposure to ionizing radiation and long-term risk of
      pre-senile cataract. The risk of cataract increased with increasing exposure,
      beginning at lens doses as low as 0.5 Gy. Our findings are in agreement with a
      growing body of evidence of an elevated risk for lens opacities in populations
      exposed to doses of ionizing radiation below the previously suggested threshold
      level of 2 Gy.

PMID- 27023265
TI  - The Effects of Antidepressants and Quetiapine on Heart Rate Variability.
AB  - Introduction: The autonomic effects of antidepressants and quetiapine on heart
      rate variability (HRV) are inconsistent based on past studies. The aim of this
      study was to explore their influence on the HRV of psychiatric patients without
      psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or
      somatic symptoms, were recruited into this study. Based on their medication, 4
      groups were identified: the no antidepressant group (n=19), the SSRI group (using
      sertraline or escitalopram, n=53), the other antidepressants group (using
      venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an
      antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The
      correlations between HRV and the medication(s) used were clarified. Results:
      Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low
      frequency power (VLF) and low frequency power (LF) of HRV being significantly
      different from those of the other groups. Age and using quetiapine were found to
      be negatively correlated with TP, VLF and LF. With this study group, the
      autonomic effects of antidepressants were found not to be significant.
      Discussion: Among psychiatric patients without psychotic symptoms, quetiapine
      causes an overt decrease in HRV.

PMID- 27023266
TI  - Bioprinting: an assessment based on manufacturing readiness levels.
AB  - Over the last decade, bioprinting has emerged as a promising technology in the
      fields of tissue engineering and regenerative medicine. With recent advances in
      additive manufacturing, bioprinting is poised to provide patient-specific
      therapies and new approaches for tissue and organ studies, drug discoveries and
      even food manufacturing. Manufacturing Readiness Level (MRL) is a method that has
      been applied to assess manufacturing maturity and to identify risks and gaps in
      technology-manufacturing transitions. Technology Readiness Level (TRL) is used to
      evaluate the maturity of a technology. This paper reviews recent advances in
      bioprinting following the MRL scheme and addresses corresponding MRL levels of
      engineering challenges and gaps associated with the translation of bioprinting
      from lab-bench experiments to ultimate full-scale manufacturing of tissues and
      organs. According to our step-by-step TRL and MRL assessment, after years of
      rigorous investigation by the biotechnology community, bioprinting is on the cusp
      of entering the translational phase where laboratory research practices can be
      scaled up into manufacturing products specifically designed for individual
      patients.

PMID- 27023267
TI  - Sediment Core Sectioning and Extraction of Pore Waters under Anoxic Conditions.
AB  - We demonstrate a method for sectioning sediment cores and extracting pore waters
      while maintaining oxygen-free conditions. A simple, inexpensive system is built
      and can be transported to a temporary work space close to field sampling site(s)
      to facilitate rapid analysis. Cores are extruded into a portable glove bag, where
      they are sectioned and each 1-3 cm thick section (depending on core diameter) is
      sealed into 50 ml centrifuge tubes. Pore waters are separated with centrifugation
      outside of the glove bag and then returned to the glove bag for separation from
      the sediment. These extracted pore water samples can be analyzed immediately.
      Immediate analyses of redox sensitive species, such as sulfide, iron speciation,
      and arsenic speciation indicate that oxidation of pore waters is minimal; some
      samples show approximately 100% of the reduced species, e.g. 100% Fe(II) with no
      detectable Fe(III). Both sediment and pore water samples can be preserved to
      maintain chemical species for further analysis upon return to the laboratory. 

PMID- 27023269
TI  - Farmer Attitudes and Livestock Disease: Exploring Citizenship Behaviour and Peer
      Monitoring across Two BVD Control Schemes in the UK.
AB  - The eradication of BVD in the UK is technically possible but appears to be
      socially untenable. The following study explored farmer attitudes to BVD control
      schemes in relation to advice networks and information sharing, shared aims and
      goals, motivation and benefits of membership, notions of BVD as a priority
      disease and attitudes toward regulation. Two concepts from the organisational
      management literature framed the study: citizenship behaviour where actions of
      individuals support the collective good (but are not explicitly recognised as
      such) and peer to peer monitoring (where individuals evaluate other's behaviour).
      Farmers from two BVD control schemes in the UK participated in the study: Orkney
      Livestock Association BVD Eradication Scheme and Norfolk and Suffolk Cattle
      Breeders Association BVD Eradication Scheme. In total 162 farmers participated in
      the research (109 in-scheme and 53 out of scheme). The findings revealed that
      group helping and information sharing among scheme members was low with a
      positive BVD status subject to social censure. Peer monitoring in the form of
      gossip with regard to the animal health status of other farms was high.
      Interestingly, farmers across both schemes supported greater regulation with
      regard to animal health, largely due to the mistrust of fellow farmers following
      voluntary disease control measures. While group cohesiveness varied across the
      two schemes, without continued financial inducements, longer-term sustainability
      is questionable. 

PMID- 27023270
TI  - Light and electron microscopic observations of the reproductive swarmer cells of
      nassellarian and spumellarian polycystines (Radiolaria).
AB  - We observed reproductive swarmer cells of the nassellarian and spumellarian
      polycystine radiolarians Didymocyrtis ceratospyris, Pterocanium praetextum,
      Tetrapyle sp., and Triastrum aurivillii using light, scanning and transmission
      electron microscopy. The swarmer cells had subspherical to ovoid or spindle
      shapes with two unequal flagella tapered to whip-like ends. The cell size was
      approximately 2.5-5.5MUm long and 1.6-2.2MUm wide, which is significantly smaller
      than that of the collodarian (colonial or naked) polycystine radiolarians.
      Transmission electron microscopy revealed that the swarmer cells possessed a
      nucleus, mitochondria with tubular cristae, Golgi body, and small lipid droplets
      in the cytoplasm; they also had a large vacuole in which a single crystalline
      inclusion (approx. 1.0-1.5MUm) that was probably celestite (SrSO4) was enclosed.
      The swarmer cells were released directly from the parent cells. At that time,
      morphological change such as encystment was not observed in the parent cells, and
      the axopodia remained extended in a period of swarmer reproduction for floating
      existence. This may have prevented the polycystine swarmers from rapidly sinking
      down to great depths. Thus, we concluded that the polycystine radiolarians
      release the swarmer cells into the photic layer in the same way as the symbiotic
      acantharians. 

PMID- 27023268
TI  - Global Allergy Forum and 3rd Davos Declaration 2015: Atopic dermatitis/Eczema:
      challenges and opportunities toward precision medicine.

PMID- 27023271
TI  - [Amblyopia].

PMID- 27023272
TI  - [Diagnostic methods in the clinical evaluation of iridocorneal endothelial
      syndrome].
AB  - BACKGROUND: This article presents a patient with iridocorneal endothelial (ICE)
      syndome. CASE REPORT: A 35-year-old man presented with unilateral slightly
      decreased visual acuity. Examination by slit-lamp biomicroscopy of the affected
      eye revealed alterations to the corneal endothelial layer, which had a silver
      grey and hammered appearance. Corectopia with the pupil drawn towards an area
      with peripheral anterior synechiae could be gonioscopically detected. In vivo
      confocal microscopy of the cornea revealed alterations of the corneal endothelial
      layers of the affected eye, namely epithelization of the endothelium with
      pleomorphic epithelioid cells of irregular size and shape, indistinct borders and
      hyperreflective nuclei. CONCLUSION: In vivo confocal microscopy of the cornea is
      a sensitive diagnostic method for the rapid and early diagnosis of ICE syndrome.

PMID- 27023273
TI  - [Occlusion treatment for amblyopia. Age dependence and dose-response
      relationship].
AB  - BACKGROUND: Based on clinical experience and studies on animal models the age of
      6-7 years was regarded as the limit for treatment of amblyopia, although
      functional improvement was also occasionally reported in older patients. New
      technical developments as well as insights from clinical studies and the
      neurosciences have attracted considerable attention to this topic. OBJECTIVE:
      Various aspects of the age dependence of amblyopia treatment are discussed in
      this article, e. g. prescription, electronic monitoring of occlusion dosage,
      calculation of indicators for age-dependent plasticity of the visual system, and
      novel, alternative treatment approaches. METHODS: Besides a discussion of the
      recent literature, results of studies by our "Child Vision Research Unit" in
      Frankfurt are presented: results of a questionnaire about prescription habits
      concerning age limits of patching, electronic recording of occlusion in patients
      beyond the conventional treatment age, calculation of dose-response function and
      efficiency of patching and their age dependence. RESULTS: The results of the
      questionnaire illustrate the uncertainty about age limits of prescription with
      significant deviations from the guideline of the German Ophthalmological Society
      (DOG). Electronic recording of occlusion allowed the quantification of declining
      dose-response function and treatment efficiency between 5 and 16 years of age.
      Reports about successful treatment with conventional and novel methods in adults
      are at variance with the notion of a rigid adult visual system lacking
      plasticity. CONCLUSION: Electronic recording of patching allowed new insights
      into the age-dependent susceptibility of the visual system and contributes to a
      more evidence-based treatment of amblyopia. Alternative approaches for adults
      challenge established notions about age limits of amblyopia therapy. Further
      studies comparing different treatment options are urgently needed.

PMID- 27023274
TI  - Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed
      from Visual Awareness.
AB  - The idea that language can affect how we see the world continues to create
      controversy. A potentially important study in this field has shown that when an
      object is suppressed from visual awareness using continuous flash suppression (a
      form of binocular rivalry), detection of the object is differently affected by a
      preceding word prime depending on whether the prime matches or does not match the
      object. This may suggest that language can affect early stages of vision. We
      replicated this paradigm and further investigated whether colour terms likewise
      influence the detection of colours or colour-associated object images suppressed
      from visual awareness by continuous flash suppression. This method presents
      rapidly changing visual noise to one eye while the target stimulus is presented
      to the other. It has been shown to delay conscious perception of a target for up
      to several minutes. In Experiment 1 we presented greyscale photos of objects.
      They were either preceded by a congruent object label, an incongruent label, or
      white noise. Detection sensitivity (d') and hit rates were significantly poorer
      for suppressed objects preceded by an incongruent label compared to a congruent
      label or noise. In Experiment 2, targets were coloured discs preceded by a colour
      term. Detection sensitivity was significantly worse for suppressed colour patches
      preceded by an incongruent colour term as compared to a congruent term or white
      noise. In Experiment 3 targets were suppressed greyscale object images preceded
      by an auditory presentation of a colour term. On congruent trials the colour term
      matched the object's stereotypical colour and on incongruent trials the colour
      term mismatched. Detection sensitivity was significantly poorer on incongruent
      trials than congruent trials. Overall, these findings suggest that colour terms
      affect awareness of coloured stimuli and colour- associated objects, and provide
      new evidence for language-perception interaction in the brain. 

PMID- 27023275
TI  - An ELISA Based Binding and Competition Method to Rapidly Determine Ligand
      receptor Interactions.
AB  - A comprehensive understanding of signaling pathways requires detailed knowledge
      regarding ligand-receptor interaction. This article describes two fast and
      reliable point-by-point protocols of enzyme-linked immunosorbent assays (ELISAs)
      for the investigation of ligand-receptor interactions: the direct ligand-receptor
      interaction assay (LRA) and the competition LRA. As a case study, the ELISA based
      analysis of the interaction between different lambda interferons (IFNLs) and the
      alpha subunit of their receptor (IL28RA) is presented: the direct LRA is used for
      the determination of dissociation constants (KD values) between receptor and IFN
      ligands, and the competition LRA for the determination of the inhibitory capacity
      of an oligopeptide, which was designed to compete with the IFNLs at their
      receptor binding site. Analytical steps to estimate KD and half maximal
      inhibitory concentration (IC50) values are described. Finally, the discussion
      highlights advantages and disadvantages of the presented method and how the
      results enable a better molecular understanding of ligand-receptor interactions. 

PMID- 27023276
TI  - Use of and Self-Perceived Need for Assistive Devices in Individuals with
      Disabilities in Taiwan.
AB  - Assistive devices (ADs) can help individuals with disabilities achieve greater
      independence, and it can enhance the quality of their lives. This study
      investigated the use of and self-perceived need for ADs in individuals with
      disabilities, and determined the influence of gender, age as well as type and
      degree of disability on the use of and self-perceived need for ADs. This
      descriptive study utilized a cross-sectional survey design with a convenience
      sample of participants. A total of 1018 subjects with disabilities who visited an
      exhibition of assistive technology and two ADs research and development centers
      completed a questionnaires either by themselves or via a caregiver who completed
      the questionnaire on behalf of the subject or via interviewers trained
      specifically for this study. The Mann-Whitney U test and Kruskal-Wallis test were
      used to determine the influence of participant characteristics on the use of ADs.
      The results showed that 77.2% and 83.3% of the participants reported that they
      used and needed AD(s) to engage in activities of daily living. The mean quantity
      of the use of and self-perceived need for total types of ADs were 3.0 and 5.3,
      respectively. Participants with different disabilities reported different
      percentages of the use of various types of ADs. No difference was found between
      genders and among the age groups in the use of quantity of ADs. Individuals with
      different types and degrees of disability used different quantities of ADs.
      Participants with physical, visual and multiple disabilities used significantly
      more ADs compared to participants with intellectual disability. The total
      quantity of ADs used increased significantly with increased severity of
      disability. The mean use of assistive devices was lower compared to the mean need
      of individuals with disabilities. Further study is required to determine why
      patients feel the need for but not currently use a specific assistive device. 

PMID- 27023277
TI  - An estimate of the economic burden of vitamin D deficiency in pregnant women in
      the United Kingdom.
AB  - Pregnancy is associated with an increased risk of vitamin D deficiency beyond
      that of the general population. The aim of the current analysis was to synthesize
      the current evidence on the dose-outcome relationship of vitamin D/serum 25
      hydroxyvitamin D (25-OHD) and complications during pregnancy. An additional aim
      was to estimate the economic burden attributable to inadequate levels of serum 25
      OHD. Published literature on the effects of vitamin D supplementation/serum 25
      OHD on pregnancy complications, including randomized control trials and non
      interventional studies, was searched in bibliographic databases including Pubmed,
      Google Scholar, Scopus and EMBASE. A positive and significant treatment effect
      was obtained for pre-eclampsia (OR = 0.75 95% CI 0.662-0.843), but not for
      preterm birth (OR = 0.783, 95% CI 0.49-1.251) or small for gestational age (OR =
      0.76 95% CI 0.38-1.28). Inadequate vitamin D accounted for 14.04% of risk for pre
      eclampsia. It is estimated that addressing vitamin D inadequacy in pregnant women
      in England and Wales would reduce the number of cases of pre-eclampsia by 4126;
      and would result in a net saving of L18.6 million for the NHS in England and
      Wales. The current results suggest that based on current evidence a public health
      policy preventing vitamin D inadequacy in pregnant women is likely to have a
      positive impact on the NHS budget in England and Wales. This is contingent upon
      further evidence regarding the vitamin D dose-pregnancy outcome relationship
      becoming available.

PMID- 27023278
TI  - Effects of dietary lead exposure on vitamin levels in great tit nestlings - An
      experimental manipulation.
AB  - Exposure to metal pollution negatively affects animal physiology, including
      nutrient metabolism, but in the wild an effect can seldom be attributed to a
      single metal. Moreover, little is known about how the metabolism of vitamins,
      essential micronutrients for developing juveniles, is affected by toxic metals.
      Therefore we experimentally investigated the effects of lead (Pb), a widespread
      toxic metal, on four fat-soluble vitamins A (total and retinol), D3, E (total and
      alpha-tocopherol) and K and carotenoids (lutein, zeaxanthin and unidentified) in
      great tit (Parus major) nestlings. In addition to a control group where no Pb was
      provided, two Pb-dosed groups were compared to a metal exposed group in the
      vicinity of a Ni-Cu smelter. We examined whether Pb treatment affects vitamin
      homeostasis and how the response of Pb-treated birds relates to that of a
      population under industrial exposure of Pb and other metals. For this purpose,
      vitamin and carotenoid levels were quantified with UPLC-MS from plasma of 7 days
      old nestlings. All metal exposed groups showed increased vitamin A and retinol
      levels. However, vitamin levels were not directly associated with fecal Pb
      levels, with the exception of retinol, which was positively correlated with fecal
      Pb. Alpha-tocopherol, lutein and zeaxanthin levels were positively associated
      with body mass and wing growth rate. To conclude, Pb exposure increased plasma
      vitamin A and retinol levels while the levels of other vitamins and carotenoids
      rather reflected secondary pollution effects via differences in habitat and diet
      quality at the smelter site. Our findings suggest Pb exposed nestlings may
      allocate the vitamins needed for growth and development to fight the
      physiological stress thus compromising their fitness. 

PMID- 27023279
TI  - Detachment of fullerene nC60 nanoparticles in saturated porous media under
      flow/stop-flow conditions: Column experiments and mechanistic explanations.
AB  - This study was aimed at investigating the detachment of fullerene nC60
      nanoparticles (NPs) in saturated sand porous media under transient and static
      conditions. The nC60 NPs were first attached at primary minima of Derjaguin
      Landau-Verwey-Overbeek (DLVO) interaction energy profiles in electrolyte
      solutions with different ionic strengths (ISs). The columns were then eluted with
      deionized water to initiate nC60 NP detachment by decreasing solution IS.
      Finally, the flow of the columns was periodically interrupted to investigate nC60
      NP detachment under static condition. Our results show that the detachment of
      nC60 NPs occurred under both transient and static conditions. The detachment
      under transient conditions was attributed to the fact that the attractions acting
      on the nC60 NPs at primary minima were weakened by nanoscale physical
      heterogeneities and overcome by hydrodynamic drags at lower ISs. However, a
      fraction of nC60 NPs remained at shallow primary minima in low flow regions, and
      detached via Brownian diffusion during flow interruptions. Greater detachment of
      nC60 NPs occurred under both transient and static conditions if the NPs were
      initially retained in electrolyte solutions with lower valent cations due to
      lower attractions between the NPs and collectors. Decrease in collector surface
      chemical heterogeneities and addition of dissolved organic matter also increased
      the extent of detachment by increasing electrostatic and steric repulsions,
      respectively. While particle attachment in and subsequent detachment from
      secondary minima occur in the same electrolyte solution, our results indicate
      that perturbation in solution chemistry is necessary to lower the primary minimum
      depths to initiate spontaneous detachment from the primary minima. These findings
      have important implications for predicting the fate and transport of nC60 NPs in
      subsurface environments during multiple rainfall events and accordingly for
      accurately assessing their environmental risks. 

PMID- 27023280
TI  - Fugitive methane emissions from leak-prone natural gas distribution
      infrastructure in urban environments.
AB  - Fugitive emissions from natural gas systems are the largest anthropogenic source
      of the greenhouse gas methane (CH4) in the U.S. and contribute to the risk of
      explosions in urban environments. Here, we report on a survey of CH4 emissions
      from 100 natural gas leaks in cast iron distribution mains in Metro Boston, MA.
      Direct measures of CH4 flux from individual leaks ranged from 4.0 - 2.3 * 10(4) g
      CH4*day(-1). The distribution of leak size is positively skewed, with 7% of leaks
      contributing 50% of total CH4 emissions measured. We identify parallels in the
      skewed distribution of leak size found in downstream systems with midstream and
      upstream stages of the gas process chain. Fixing 'superemitter' leaks will
      disproportionately stem greenhouse gas emissions. Fifteen percent of leaks
      surveyed qualified as potentially explosive (Grade 1), and we found no difference
      in CH4 flux between Grade 1 leaks and all remaining leaks surveyed (p = 0.24).
      All leaks must be addressed, as even small leaks cannot be disregarded as 'safely
      leaking.' Key methodological impediments to quantifying and addressing the
      impacts of leaking natural gas distribution infrastructure involve
      inconsistencies in the manner in which gas leaks are defined, detected, and
      classified. To address this need, we propose a two-part leak classification
      system that reflects both the safety and climatic impacts of natural gas leaks. 

PMID- 27023281
TI  - Temporal trends and spatial variation characteristics of primary air pollutants
      emissions from coal-fired industrial boilers in Beijing, China.
AB  - Coal-fired combustion is recognized as a significant anthropogenic source of
      atmospheric compounds in Beijing, causing heavy air pollution events and
      associated deterioration in visibility. Obtaining an accurate understanding of
      the temporal trends and spatial variation characteristics of emissions from coal
      fired industrial combustion is essential for predicting air quality changes and
      evaluating the effectiveness of current control measures. In this study, an
      integrated emission inventory of primary air pollutants emitted from coal-fired
      industrial boilers in Beijing is developed for the period of 2007-2013 using a
      technology-based approach. Future emission trends are projected through 2030
      based on current energy-related and emission control policies. Our analysis shows
      that there is a general downward trend in primary air pollutants emissions
      because of the implementation of stricter local emission standards and the
      promotion by the Beijing municipal government of converting from coal-fired
      industrial boilers to gas-fired boilers. However, the ratio of coal consumed by
      industrial boilers to total coal consumption has been increasing, raising
      concerns about the further improvement of air quality in Beijing. Our estimates
      indicate that the total emissions of PM10, PM2.5, SO2, NOx, CO and VOCs from coal
      fired industrial boilers in Beijing in 2013 are approximately 19,242 t, 13,345 t,
      26,615 t, 22,965 t, 63,779 t and 1406 t, respectively. Under the current
      environmental policies and relevant energy savings and emission control plans, it
      may be possible to reduce NOx and other air pollutant emissions by 94% and 90% by
      2030, respectively, if advanced flue gas purification technologies are
      implemented and coal is replaced with natural gas in the majority of existing
      boilers. 

PMID- 27023282
TI  - The Kuril Islands as a potential region for aquaculture: Trace elements in chum
      salmon.
AB  - The Kuril Islands region is considered promising for development of salmon
      aquaculture. There are 41 salmon fish hatcheries in the Sakhalin Island and the
      Kuril Islands, 34 of them are hatcheries of the chum. Therefore, concentrations
      of six elements (Zn, Cu, Cd, Pb, As, and Hg) were determined in chum salmon were
      caught in this region. The contents of toxic elements (Cd, Pb, As, and Hg) don't
      exceed their maximum permissible concentrations (MPC) according to the Russian
      sanitary standards, but concentration of Pb are closely to MPC. Increased
      concentrations of Pb in wild chum have the natural origin. The unusual conditions
      of the Western Pacific are formed under the influence such factors as volcanism
      and upwelling. 

PMID- 27023283
TI  - Current status and prospects of HIV treatment.
AB  - Current antiviral treatments can reduce HIV-associated morbidity, prolong
      survival, and prevent HIV transmission. Combination antiretroviral therapy (cART)
      containing preferably three active drugs from two or more classes is required for
      durable virologic suppression. Regimen selection is based on virologic efficacy,
      potential for adverse effects, pill burden and dosing frequency, drug-drug
      interaction potential, resistance test results, comorbid conditions, social
      status, and cost. With prolonged virologic suppression, improved clinical
      outcomes, and longer survival, patients will be exposed to antiretroviral agents
      for decades. Therefore, maximizing the safety and tolerability of cART is a high
      priority. Emergence of resistance and/or lack of tolerability in individual
      patients require availability of a range of treatment options. Development of new
      drugs is focused on improving safety (e.g. tenofovir alafenamide) and/or
      resistance profile (e.g. doravirine) within the existing drug classes,
      combination therapies with improved adherence (e.g. single-tablet regimens),
      novel mechanisms of action (e.g. attachment inhibitors, maturation inhibitors,
      broadly neutralizing antibodies), and treatment simplification with infrequent
      dosing (e.g. long-acting injectables). In parallel with cART innovations,
      research and development efforts focused on agents that target persistent HIV
      reservoirs may lead to prolonged drug-free remission and HIV cure.

PMID- 27023285
TI  - Strategies to target non-T-cell HIV reservoirs.
AB  - PURPOSE OF REVIEW: A central question for the HIV cure field is to determine new
      ways to target clinically relevant, latently and actively replicating HIV
      infected cells beyond resting memory CD4 T cells, particularly in anatomical
      areas of low drug penetrability. RECENT FINDINGS: HIV eradication strategies
      being positioned for targeting HIV for extinction in the CD4 T-cell compartment
      may also show promise in non-CD4 T-cells reservoirs. Furthermore, several
      exciting novel therapeutic approaches specifically focused on HIV clearance from
      non-CD4 T-cell populations are being developed. SUMMARY: Although reservoir
      validity in these non-CD4 T cells continues to remain debated, this review will
      highlight recent advances and make an argument as to their clinical relevancy as
      we progress towards an HIV cure.

PMID- 27023284
TI  - Bone health and HIV in resource-limited settings: a scoping review.
AB  - PURPOSE OF REVIEW: Sub-Saharan Africa and other resource-limited settings (RLS)
      bear the greatest burden of the HIV epidemic globally. Advantageously, the
      expanding access to antiretroviral therapy (ART) has resulted in increased
      survival of HIV individuals in the last 2 decades. Data from resource rich
      settings provide evidence of increased risk of comorbid conditions such as
      osteoporosis and fragility fractures among HIV-infected populations. We provide
      the first review of published and presented data synthesizing the current state
      of knowledge on bone health and HIV in RLS. RECENT FINDINGS: With few exceptions,
      we found a high prevalence of low bone mineral density (BMD) and hypovitaminosis
      D among HIV-infected populations in both RLS and resource rich settings. Although
      most recognized risk factors for bone loss are similar across settings, in
      certain RLS there is a high prevalence of both non-HIV-specific risk factors and
      HIV-specific risk factors, including advanced HIV disease and widespread use of
      ART, including tenofovir disoproxil fumarate, a non-BMD sparing ART. Of great
      concern, we neither found published data on the effect of tenofovir disoproxil
      fumarate initiation on BMD, nor any data on incidence and prevalence of fractures
      among HIV-infected populations in RLS. SUMMARY: To date, the prevalence and
      squeal of metabolic bone diseases in RLS are poorly described. This review
      highlights important gaps in our knowledge about HIV-associated bone health
      comorbidities in RLS. This creates an urgent need for targeted research that can
      inform HIV care and management guidelines in RLS.

PMID- 27023286
TI  - Diversity of HIV-1 reservoirs in CD4+ T-cell subpopulations.
AB  - PURPOSE OF REVIEW: HIV-1 is able to create lasting reservoirs of virally infected
      cells that persist life-long and are extremely difficult to eradicate, thus
      necessitating indefinite antiretroviral therapy. Large numbers of studies suggest
      that CD4 T cells represent the major, and possibly the only cell type supporting
      HIV-1 long-term persistence. However, the ability to serve as long-term viral
      reservoirs may be confined to certain subpopulations of CD4 T cells with specific
      functional and developmental characteristics that HIV-1 can selectively exploit
      to propagate long-term viral survival within the host. Identification of CD4 T
      cell subtypes that serve as hotspots for viral persistence may be critical for
      designing strategies to purge the immune system of persisting viral reservoirs.
      RECENT FINDINGS: Developmentally immature, long-lasting CD4 memory T-cell
      populations seem to contain the majority of latently HIV-1-infected cells that
      persist despite antiretroviral therapy in the peripheral blood. Emerging data
      suggest that functional polarization toward a T helper 17 (Th17), a T follicular
      helper cell or a regulatory T-cell lineage may also be associated with an
      increased ability to serve as a viral reservoir site. Atypical T cells such a
      gammadelta CD4 T cells or tissue-resident memory CD4 T cells may be predestined
      to serve as sites for HIV-1 persistence in specific tissues, but will require
      additional exploration in future studies. SUMMARY: Recent advances have increased
      awareness for the profound diversity and complexity of CD4 T-cell subpopulations
      serving as sites for HIV-1 persistence. Continuous technological and
      methodological improvements to interrogate viral reservoirs in distinct CD4 T
      cell subpopulations may allow to define a more complete landscape of the HIV-1
      reservoir composition in different T-cell subpopulations.

PMID- 27023287
TI  - Long-Term Care Providers and services users in the United States: data from the
      National Study of Long-Term Care Providers, 2013-2014.
AB  - Long-term care services provided by paid, regulated providers are an important
      component of personal health care spending in the United States. This report
      presents the most current national descriptive results from the National Study of
      Long-Term Care Providers (NSLTCP), which is conducted by the Centers for Disease
      Control and Prevention's National Center for Health Statistics (NCHS). Data
      presented are drawn from multiple sources, primarily NCHS surveys of adult day
      services centers and residential care communities (covers 2014 data year); and
      administrative records obtained from the Centers for Medicare and Medicare
      Services (CMS) on home health agencies, hospices, and nursing homes (covers 2013
      and 2014 data years). This report provides information on the supply,
      organizational characteristics, staffing, and services offered by paid, regulated
      providers of long-term care services; and the demographic, health, and functional
      composition of users of these services. Services users include residents of
      nursing homes and residential care communities, patients of home health agencies
      and hospices, and participants of adult day services centers. This report updates
      "Long-Term Care Services in the United States: 2013 Overview" (available from:
      http://www.cdc.gov/nchs/data/nsltcp/long_term_care_services_2013.pdf), which
      covered data years 2011 and 2012. In contrast, the title of this report and
      future reports will reflect the years of the data used rather than the
      publication year, in this case 2013 through 2014. A forthcoming companion product
      to this report, "Long-Term Care Providers and Services Users in the United States
      State Estimates Supplement: National Study of Long-Term Care Providers, 2013
      2014," contains tables and maps showing comparable state estimates for the
      national findings in this report, and will be available from:
      http://www.cdc.gov/nchs/ nsltcp/nsltcp_products.htm.

PMID- 27023288
TI  - Conservation Research Is Not Happening Where It Is Most Needed.
AB  - Target 19, set by the Convention on Biological Diversity, seeks to improve the
      knowledge, science base, and technologies relating to biodiversity. We will fail
      to achieve this target unless prolific biases in the field of conservation
      science are addressed. We reveal that comparatively less research is undertaken
      in the world's most biodiverse countries, the science conducted in these
      countries is often not led by researchers based in-country, and these scientists
      are also underrepresented in important international fora. Mitigating these
      biases requires wide-ranging solutions: reforming open access publishing
      policies, enhancing science communication strategies, changing author attribution
      practices, improving representation in international processes, and strengthening
      infrastructure and human capacity for research in countries where it is most
      needed. 

PMID- 27023289
TI  - Presence of scapular dysfunction in dominant shoulder of professional guitar
      players.
AB  - BACKGROUND: Playing guitar can cause adoption of asymmetric postures and affect
      the shoulder's stability. OBJECTIVE: To assess the presence of scapular
      dysfunction in professional guitar players. METHOD: A lateral scapular slide test
      was performed at the level of the spine of the scapula and at the inferior angle
      of the scapula in 20 professional guitar players (age: 18-40 years) and was
      compared with 20 age-matched non-players at angles of 0 degrees , 45 degrees  and
      90 degrees  of shoulder abduction with both limbs loaded with 0.5-kg weights.
      Analysis was done by unpaired t test. RESULTS: Scapular dysfunction in guitar
      players was seen in the form of asymmetric scapula at rest in 25% and dyskinetic
      scapula in 20% of players. 100% of non-players had normal scapular positioning.
      Comparison at the level of the spine of the scapula showed no significant
      difference (p > 0.05), but the inferior angle showed a significant difference at
      0 degrees  (1.37 cm), 45 degrees  (1.93 cm) and 90 degrees  (2.15 cm) which was
      more in the player's category (p < 0.05). CONCLUSION: There exists a marked
      dysfunction of scapular stabilizers in professional guitar players at the level
      of the inferior angle of the scapula.

PMID- 27023290
TI  - Characterization of topological phases in the compass ladder model.
AB  - The phase diagram of the quantum compass ladder model is investigated through
      numerical density matrix renormalization group based on infinite matrix product
      state algorithm and analytic effective perturbation theory. For this model we
      obtain two symmetry-protected topological phases, protected by a Z2 * Z2
      symmetry, and a topologically-trivial Z2-symmetry-breaking phase. The symmetry
      protected topological phases--labeled by symmetry fractionalization--belong to
      different topological classes, where the complex-conjugate symmetry uniquely
      distinguishes them. An important result of this classification is that, as
      revealed by the nature of the Z2-symmetry-breaking phase, the associated quantum
      phase transitions are accompanied by an explicit symmetry breaking, and thus a
      local-order parameter conclusively identifies the phase diagram of the underlying
      model. This is in stark contrast to previous studies which require a non-local
      string order parameter to distinguish the corresponding quantum phase
      transitions. We numerically examine our results and show that the local-order
      parameter is related to the magnetization exponent 0.12 +/- 0.01.

PMID- 27023291
TI  - Unsung Heroes.

PMID- 27023293
TI  - Best Practices for the Identification of Elder Abuse and Neglect in Home Health.
AB  - Elder abuse and neglect (EA/N) affects over 1 million older adults each year, and
      disproportionately affects persons with dementia and older women. Home healthcare
      professionals are in an advantageous position to assess for, identify, and report
      EA/N. Lack of knowledge on EA/N risk factors, assessment tools, and mandatory
      reporting guidelines often prevent professionals from identifying and reporting
      EA/N. This article provides practical guidance on EA/N risk factors, assessment
      tools, and reporting responsibilities that can easily be implemented in practice.

PMID- 27023294
TI  - Home Health Aides' Experience With Client Death: The Role of Employer Policy.
AB  - Home health aides (HHAs) are members of a rapidly growing occupation. They often
      develop close ties to patients and their family and can experience significant
      grief when a patient dies. Yet agencies often provide little support or structure
      to help staff cope during this time. For instance, home care agencies do not
      always notify their staff of client death and some have policies in place to
      prevent any follow-up contact with a deceased client's family. Little is known
      about how these agency factors affect HHAs' work experience. This mixed-method
      study explored the experiences of 78 HHAs working either at an agency with a
      restrictive policy regarding contact with a client's family after client death or
      an agency without such a policy in place. Data were collected through
      semistructured in-person interviews. Employment outcomes included various aspects
      of job satisfaction and intention to change jobs. HHAs' responses to client death
      were assessed with measures of grief and grief processing, and with open-ended
      questions exploring their experiences in this context. Findings indicated that
      HHAs from the restrictive agency were significantly more likely to be considering
      other job options. They also reported significantly lower satisfaction with
      received supervision, and significantly less grief processing activity. Findings
      suggest that HHAs from the agency without a contact-restrictive policy had a more
      positive experience at work and more opportunity to process the client's death. 

PMID- 27023295
TI  - The Lived Experience of African American Caregivers Caring for Adult African
      American Patients With Heart Failure.
AB  - Assistance from informal caregivers such as family members, friends, or neighbors
      is crucial to adequately managing the complex care of heart failure (HF)
      patients. This study examined the lived experience of African American caregivers
      caring for African American patients with HF. Purposive sampling was used to
      recruit 10 participants who were formally interviewed. The interviews, analyzed
      using Colaizzi's steps, revealed six themes: layers of support, realization of
      self-neglect, experiencing the "blues," connecting with healthcare providers,
      unmet financial needs, and perception of nonadherence. The information regarding
      the experience of African American caregivers of HF patients obtained through
      this research will inform the delivery of culturally competent support to
      caregivers, thereby improving quality of life for both the HF patients and their
      caregivers. 

PMID- 27023296
TI  - Helping Dementia Caregivers Through Technology.
AB  - It is estimated there are between 43.5 and 65.7 million caregivers in the United
      States who provide unpaid care for older adults. Although the number of informal
      caregivers is expected to continue to increase, few programs have been
      established in home healthcare agencies to support these caregivers. This article
      describes a project that used a unique Web site to connect caregivers of people
      with dementia in a geographic region with an interprofessional group of
      healthcare providers and caregiver peers. Virtual Healthcare Neighborhood (VHN)
      was developed and maintained by an interprofessional group of healthcare
      providers from nursing, physical therapy, clinical counseling, and dental
      hygiene. The VHN provided weekly information on topics relevant to caring for a
      loved one with dementia at home as well as Question and Answer and Social Support
      Blogging sections for use by participants. This project was viewed as a positive
      and helpful method to provide support for caregivers of homebound older adults
      that could be easily replicated by home healthcare agencies. 

PMID- 27023297
TI  - Knowledge, Attitude, and Practices Toward Blood Pressure Measurement at Home
      Among Japanese Nurses.
AB  - The self-measurement of blood pressure (BP) at home is useful in predicting the
      level of target organ damage and in managing hypertension. Nurses are essential
      practitioners for managing hypertension; however, it is unclear whether they have
      adequate knowledge of home BP management. This study assessed the knowledge,
      attitudes, and practices of home BP measurement among Japanese nurses. A
      questionnaire regarding home BP measurement was distributed among nurses and
      collected by mail. A total of 6,002 (61.8%) responses were eligible for the
      study. The proportion of participants who correctly recognized the reference
      values for clinic BP and home BP was 9.9% and 2.8%. Midwives and those working
      for the government had the highest proportion of correct responses of reference
      values among all nursing subgroups. Participants who thought that home BP gave
      the most important BP information were 62.7%. About 60% of the participants who
      recommended home BP measurement to hypertensive patients preferred to recommend
      an upper-arm cuff device. Our findings suggested that more knowledge of home BP
      measurement among nurses is warranted. 

PMID- 27023298
TI  - Administering Just the Diluent or One of Two Vaccine Components Leaves Patients
      Unprotected.

PMID- 27023299
TI  - Preventing Contamination of Portable Computers.

PMID- 27023300
TI  - A Day in the Life of a Home Health Wound Care Nurse.

PMID- 27023301
TI  - What Are Podcasts?

PMID- 27023302
TI  - Non-Legal Advocacy to Improve Quality of Care.

PMID- 27023303
TI  - It's Time to Talk: Starting a Conversation About Discontinuing Medications at End
      of Life.

PMID- 27023304
TI  - What Is Your Professional Name and Title?

PMID- 27023307
TI  - Optic Nerve Fenestration in a Patient With the Syndrome of Acquired Hyperopia and
      Choroidal Folds.
AB  - We performed bilateral optic nerve sheath fenestrations on a patient with the
      syndrome of acquired hyperopia and choroidal folds. We are unaware of previous
      reports of this procedure being performed in this clinical setting. Despite the
      incomplete resolution of his posterior segment findings postoperatively, the
      results of the procedure, along with an understanding of the relevant anatomy,
      may help to shed light on the pathogenesis of this rare entity.

PMID- 27023306
TI  - Physical activity levels and perceived benefits and barriers to physical activity
      in HIV-infected women living in the deep south of the United States.
AB  - Engaging in regular physical activity (PA) is important in maintaining health and
      increasing the overall quality of life of people living with HIV (PLWH). The deep
      south of the USA is known for its high rate of sedentary behavior although data
      on the activity levels and perceptions of the benefits and barriers to exercise
      in women living with HIV in the deep south are lacking. Understanding the
      perceived benefits and barriers to exercise can guide the development of PA
      interventions. We conducted a cross-sectional study to determine the PA levels
      and perceived benefits and barriers to exercise associated with both age and
      depression level in a group of HIV+ women living in the deep south. We recruited
      a total of 50 participants from a cohort site for the Women's Interagency HIV
      Study. Depression was assessed using the Center for Epidemiological Studies
      Depression Scale (CES-D) and benefits/barriers to exercise were measured using
      the Exercise Benefits and Barriers Scale (EBBS). We measured PA both subjectively
      and objectively using the International Physical Activity Questionnaire (IPAQ)
      and a Fitbit PA monitor, respectively. Our sample was predominantly African
      American (96%) and the mean +/-SD age, body mass index, and CES-D score were 42
      +/- 8.8 years, 36.6 +/- 11.5 kg/m(2), and 15.6 +/- 11.4, respectively. Both
      subjective and objective measures of PA indicated that our participants were
      sedentary. The greatest perceived benefit to exercise was physical performance
      and the greatest barrier to exercise was physical exertion. Higher overall
      perceived benefits were reported by women >=43 years and women reporting higher
      levels of depression. There was no difference in overall barriers associated with
      age and depression level, but women with depression felt more fatigued by
      exercise. The results of this study can be helpful when designing and
      implementing PA interventions in women living with HIV in the deep south.

PMID- 27023308
TI  - The Relationship Between Optic Nerve Sheath Decompression Failure and
      Intracranial Pressure in Idiopathic Intracranial Hypertension.
AB  - BACKGROUND: To our knowledge, there are no studies of patients with idiopathic
      intracranial hypertension (IIH) that address the relationship between level of
      intracranial pressure (ICP) and likelihood of progressive visual loss despite
      uncomplicated optic nerve sheath decompression (ONSD). This study investigated
      whether patients with IIH undergoing ONSD had a higher risk of surgical failure
      if opening pressure (OP) on lumbar puncture was >=50 cm H2O compared to those
      with OP <50 cm H2O. METHODS: We conducted a retrospective chart review of
      consecutive patients with IIH who failed maximal medical therapy and underwent
      ONSD between January, 1992 and November, 2014, and were followed at least 3
      months postoperatively. The main outcome measure was the relationship between OP
      on lumbar puncture and ONSD failure. We also investigated the relationship of OP
      with visual acuity, visual fields, age, and gender. RESULTS: During this period,
      174 patients met inclusion criteria. Of the 40 patients who had an OP >=50 cm
      H2O, 6 (15%) had progressive visual loss after uncomplicated ONSD, vs 6 (4.5%) of
      134 patients with an OP <50 cm H2O (P = 0.032, Fisher exact test). Patients with
      worse visual acuity at presentation also had a higher risk of progressive visual
      loss after ONSD (P < 0.001, Cochran-Armitage trend test), as did men (P = 0.048,
      Fisher exact test). CONCLUSIONS: Patients with IIH and an OP >=50 cm H2O had a 3
      fold increased risk of failure of ONSD to prevent progressive visual loss,
      requiring a shunting procedure when compared to those with OP <50 cm H2O. Visual
      acuity at presentation and male sex also were associated with progressive visual
      decline after ONSD. These risk factors merit closer follow-up in the
      postoperative period when signs of further visual deterioration would indicate an
      urgent need for neurosurgical shunting.

PMID- 27023309
TI  - Opsoclonus-Myoclonus Syndrome in Primary Central Nervous System Lymphoma.
AB  - Adult-onset opsoclonus-myoclonus syndrome (OMS) has been associated with multiple
      cancers, most commonly small-cell lung carcinoma and breast adenocarcinoma. A 53
      year-old woman who presented with OMS was found to have primary central nervous
      system (CNS) diffuse large B-cell lymphoma. OMS has been described in only 5
      cases with non-Hodgkin lymphoma (NHL), and this is only the third reported case
      of OMS in NHL limited to the CNS. Although the paraneoplastic antibody panel was
      negative, we presume that the OMS was a paraneoplastic manifestation.
      Antineoplastic and anti-immune therapy had no effect on the neurologic
      manifestations.

PMID- 27023310
TI  - Strabismus Surgery in Patients With Ocular Neuromyotonia: Potential Unmasking of
      the Condition and Effective Management Tool.
AB  - BACKGROUND: Ocular neuromyotonia (ONM) is a rare motility disorder in which
      paroxysms of tonic extraocular muscle contraction from abnormal ocular motor
      nerve firing result in episodic diplopia and strabismus. Medical therapy with
      membrane-stabilizing agents has varied success. A surgical approach to treatment
      has not yet been described. We report the outcomes of strabismus surgery in
      patients with ONM. METHODS: We describe 3 patients with sixth nerve paresis and
      ONM of the affected lateral rectus muscle who underwent strabismus surgery. All
      patients had a history of radiation therapy for intracranial tumors.
      Ophthalmologic and orthoptic examinations were performed with appropriate medical
      and neuroradiologic evaluation. Preoperative and postoperative data are presented
      and analyzed. RESULTS: Two patients were noted to have ONM after their first
      strabismus surgery for a sixth nerve palsy. Patients 1 and 2 had 3 surgeries,
      whereas Patient 3 had 1 operation. Extraocular muscles operated on included the
      medial rectus and lateral rectus. Preoperative primary gaze baseline esotropia
      ranged from 35 to 75 prism diopters (Delta). All patients achieved improvement in
      ocular alignment and motility. Postoperative primary gaze deviations ranged from
      orthotropia to 20Delta of esotropia. Abduction deficits were unchanged or
      improved. The follow-up period ranged from 15 months to 2 years. CONCLUSIONS:
      Patients with ONM of a paretic rectus muscle can achieve binocular fusion with
      strabismus surgery. ONM may manifest postoperatively in patients with a sixth
      nerve palsy and a contractured medial rectus who, preoperatively, were not noted
      to have ONM.

PMID- 27023311
TI  - Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast
      Cancer.
AB  - With the advent of the -omics approaches our understanding of the chronic
      diseases like cancer and metabolic syndrome has improved. However, effective
      mining of the information in the large-scale datasets that are obtained from gene
      expression microarrays, deep sequencing experiments or metabolic profiling is
      essential to uncover and then effectively target the critical regulators of
      diseased cell phenotypes. Estrogen Receptor alpha (ERalpha) is one of the master
      transcription factors regulating the gene programs that are important for
      estrogen responsive breast cancers. In order to understand to role of ERalpha
      signaling in breast cancer metabolism we utilized transcriptomic, cistromic and
      metabolomic data from MCF-7 cells treated with estradiol. In this report we
      described generation of samples for RNA-Seq, ChIP-Seq and metabolomics
      experiments and the integrative computational analysis of the obtained data. This
      approach is useful in delineating novel molecular mechanisms and gene regulatory
      circuits that are regulated by a particular transcription factor which impacts
      metabolism of normal or diseased cells. 

PMID- 27023312
TI  - Demonstrating Your Clinical Competence in Women's Health Campbell Pam et al
      Demonstrating Your Clinical Competence in Women's Health 216pp Radcliffe
      Publishing 9781857756050 1857756053.
AB  - This book links clinical practice and personal development for nurses to create a
      meaningful portfolio. It discusses the lifelong learning process, how to
      demonstrate clinical competence, identifying personal needs, the delivery of care
      and gaps in service delivery. Individual performance reviews are explained fully.

PMID- 27023313
TI  - Intermediate Care of Older People Wade Sian (ed) Intermediate Care of Older
      People 334pp Whurr Publishers 9781861563569 1861563566.
AB  - Intermediate care is an elusive concept. In this well-written, comprehensive
      volume, Sian Wade sheds much light on the subject.

PMID- 27023314
TI  - Access to Diverse Oxygen Heterocycles via Oxidative Rearrangement of Benzylic
      Tertiary Alcohols.
AB  - A facile method for the synthesis of challenging medium-sized cyclic ethers has
      been developed via a novel oxidative rearrangement of benzylic tertiary alcohols.
      The reaction provides access to cyclic acetals with diverse substitution at both
      C2 and the aromatic ring. The unique reactivity is enabled by poly(cationic)
      hypervalent iodine reagents and represents the first synthetic application of
      this underexplored class of compounds. 

PMID- 27023315
TI  - High-Throughput Screening of Saturated Fatty Acid Influence on Nanostructure of
      Lyotropic Liquid Crystalline Lipid Nanoparticles.
AB  - Self-assembled lyotropic liquid crystalline lipid nanoparticles have been
      developed for a wide range of biomedical applications with an emerging focus for
      use as delivery vehicles for drugs, genes, and in vivo imaging agents. In this
      study, we report the generation of lipid nanoparticle libraries with information
      regarding mesophase and lattice parameter, which can aid the selection of
      formulation for a particular end-use application. In this study we elucidate the
      phase composition parameters that influence the internal structure of lipid
      nanoparticles produced from monoolein, monopalmitolein and phytantriol
      incorporating a variety of saturated fatty acids (FA) with different chain
      lengths at varying concentrations and temperatures. The material libraries were
      established using high throughput formulation and screening techniques, including
      synchrotron small-angle X-ray scattering. The results demonstrate the rich
      polymorphism of lipid nanoparticles with nonlamellar mesophases in the presence
      of saturated FAs. The inclusion of saturated FAs within the lipid nanoparticles
      promotes a gradual phase transition at all temperatures studied toward structures
      with higher negative surface curvatures (e.g., from inverse bicontinuous cubic
      phase to hexagonal phase and then emulsified microemulsion). The three partial
      phase diagrams produced are discussed in terms of the influence of FA chain
      length and concentration on nanoparticle internal mesophase structure and lattice
      parameters. The study also highlights a compositionally dependent coexistence of
      multiple mesophases, which may indicate the presence of multicompartment
      nanoparticles containing cubic/cubic and cubic/hexagonal mesophases.

PMID- 27023316
TI  - Optical Coherence Tomography Angiography of Miscellaneous Retinal Disease.
AB  - In this chapter, we illustrate different clinical scenarios using swept-source
      optical coherence tomography angiography (OCTA, Triton, Topcon, Inc., Tokyo,
      Japan). The instrument is based on a long wavelength scanning light (1,050 nm)
      that can better penetrate the deeper ocular layers, such as the choroid and
      sclera. Our aim was to show how OCTA can be used to study the eye vascular
      network in a novel and innovative fashion. We have demonstrated that a specific
      disease can involve one or more layers; conversely, the same layer may be
      affected by different ocular pathologies. Moreover, we would like to stress that
      knowledge of disease pathophysiology is fundamental, and thus, we have focused
      our attention on the layer(s) most involved in each pathological condition. In
      some miscellaneous cases, the swept-source OCTA findings have corroborated with
      conventional imaging data (i.e. fundus photography, B-scan ultrasonography,
      fluorangiography and indocyanine green angiography), thus leading us to the
      proper diagnosis. 

PMID- 27023317
TI  - Effect of toe extension on EMG of triceps surae muscles during isometric
      dorsiflexion.
AB  - The protocol for estimating force of contraction by triceps surae (TS) muscles
      requires the immobilization of the ankle during dorsiflexion and plantar flexion.
      However, large variability in the results has been observed. To identify the
      cause of this variability, experiments were conducted where ankle dorsiflexion
      force and electromyogram (EMG) of the TS were recorded under two conditions: (i)
      toes were strapped and (ii) toes were unstrapped, with all other conditions such
      as immobilization of the ankle remaining unchanged. The root mean square (RMS) of
      the EMG and the force were analyzed and one-tail Student's t-test was performed
      for significance between the two conditions. The RMS of the EMG from TS muscles
      was found to be significantly higher (~55%) during dorsiflexion with toes
      unstrapped compared with when the toes were strapped. The torque corresponding to
      dorsiflexion was also higher with toes unstrapped. Our study has shown that it is
      important to strap the toes when measuring the torque at the ankle and EMG of the
      TS muscles.

PMID- 27023318
TI  - Some rape/canola seed oils: fatty acid composition and tocopherols.
AB  - Seed samples of some rape and canola cultivars were analysed for oil content,
      fatty acid and tocopherol profiles. Gas liquid chromotography and high
      performance liquid chromotography were used for fatty acid and tocopherol
      analysis, respectively. The oil contents of rape and canola seeds varied between
      30.6% and 48.3% of the dry weight (p<0.05). The oil contents of rapeseeds were
      found to be high compared with canola seed oils. The main fatty acids in the oils
      are oleic (56.80-64.92%), linoleic (17.11-20.92%) and palmitic (4.18-5.01%)
      acids. A few types of tocopherols were found in rape and canola oils in various
      amounts: alpha-tocopherol, gamma-tocopherol, delta-tocopherol, beta-tocopherol
      and alpha-tocotrienol. The major tocopherol in the seed oils of rape and canola
      cultivars were alpha-tocopherol (13.22-40.01%) and gamma-tocopherol (33.64
      51.53%) accompanied by alpha-T3 (0.0-1.34%) and delta-tocopherol (0.25-1.86%)
      (p<0.05). As a result, the present study shows that oil, fatty acid and
      tocopherol contents differ significantly among the cultivars. 

PMID- 27023319
TI  - The physico-chemical properties of some citrus seeds and seed oils.
AB  - The chemical properties, mineral contents, fatty acid and tocopherol contents of
      seed and seed oils of some citrus genus provided from several locations in Turkey
      and Saudi Arabia were determined. While Ca contents of seeds were between 5018
      mg/kg (Kutdiken lemon) and 7619 mg/kg (kinnow mandarin), K contents of seeds
      varied between 7007 mg/kg (Orlando orange) and 10334 mg/kg (kinnow mandarin).
      Glucose and fructose contents of citrus seed samples varied between 3.75 g/kg and
      5.75 g/kg, and 4.09 g/kg and 6.03 g/kg. Palmitic, oleic and linoleic acids were
      established as dominant fatty acids. Palmitic, oleic and linoleic acid contents
      of citrus seed oils varied between 19.6% (Kutdiken lemon) and 26.2% (pineapple
      orange), 21.3% (kinnow mandarin) and 31.4% (Kutdiken lemon) and 32.3% (Kutdiken
      lemon) and 43.7% (kinnow mandarin), respectively. The total amount of tocopherols
      of Turkish citrus oil varied between 0.5 mg/100 g (Fremont mandarin) and 18.8
      mg/100 g (bitter orange). 

PMID- 27023320
TI  - Evaluation of an automated urinary iodine measurement using AU5800 analyzer with
      AutoLab Iodine reagent.

PMID- 27023321
TI  - The Introduction of "Safety Science" into an Undergraduate Nursing Programme at a
      Large University in the United Kingdom.
AB  - Implementing safety science {a term adopted by the authors which incorporates
      both patient safety and human factors (Sherwood, G. (2011). Integrating quality
      and safety science in nursing education and practice. Journal of Research in
      Nursing, 16(3), 226-240. doi: 10.1177/1744987111400960)} into healthcare
      programmes is a major challenge facing healthcare educators worldwide (National
      Advisory Group on the Safety of Patients in England, 2013; World Health
      Organisation, 2009). Patient safety concerns relating to human factors have been
      well-documented over the years, and the root cause(s) of as many as 65-80 % of
      these events are linked to human error (Dunn et al., 2007; Reason, 2005). This
      paper will describe how safety science education was embedded into a pre
      registration nursing programme at a large UK university. The authors argue that
      the processes described in this paper, may be successfully applied to other pre
      registration healthcare programmes in addition to nursing. 

PMID- 27023322
TI  - Model selection for factorial Gaussian graphical models with an application to
      dynamic regulatory networks.
AB  - Factorial Gaussian graphical Models (fGGMs) have recently been proposed for
      inferring dynamic gene regulatory networks from genomic high-throughput data. In
      the search for true regulatory relationships amongst the vast space of possible
      networks, these models allow the imposition of certain restrictions on the
      dynamic nature of these relationships, such as Markov dependencies of low order -
      some entries of the precision matrix are a priori zeros - or equal dependency
      strengths across time lags - some entries of the precision matrix are assumed to
      be equal. The precision matrix is then estimated by l1-penalized maximum
      likelihood, imposing a further constraint on the absolute value of its entries,
      which results in sparse networks. Selecting the optimal sparsity level is a major
      challenge for this type of approaches. In this paper, we evaluate the performance
      of a number of model selection criteria for fGGMs by means of two simulated
      regulatory networks from realistic biological processes. The analysis reveals a
      good performance of fGGMs in comparison with other methods for inferring dynamic
      networks and of the KLCV criterion in particular for model selection. Finally, we
      present an application on a high-resolution time-course microarray data from the
      Neisseria meningitidis bacterium, a causative agent of life-threatening
      infections such as meningitis. The methodology described in this paper is
      implemented in the R package sglasso, freely available at CRAN, http://CRAN.R
      project.org/package=sglasso.

PMID- 27023323
TI  - Determination of methanol in Iranian herbal distillates.
AB  - BACKGROUND: Herbal distillates have been used as beverages, for flavoring, or as
      phytomedicines in many countries for a long time. Recently, the occurrence of
      blindness after drinking herbal distillates has created concerns in Iran. The aim
      of this study was to determine the concentrations of methanol in herbal
      distillates produced in Iran. METHODS: Eighty-four most commonly used herbal
      distillates purchased from herbal distillate factories were analyzed for methanol
      contents by gas chromatography and flame ionization detection, with ethanol as
      internal standard. RESULTS: In 15 herbal distillates, the methanol concentration
      was below the limit of quantitation. The methanol concentrations in all samples
      ranged from 43 to 277 mg/L. Forty-five samples contained methanol in excess of
      the Iranian standard. The maximum concentration was found in an herbal distillate
      of Mentha piperita (factory E) (277+/-12), and the minimum in a distillate of
      Carum carvi (factory B) (42.6 +/- 0.5). CONCLUSIONS: Since the 45 Iranian herbal
      distillates containing methanol levels were beyond the legal limits according to
      the Iranian standard, it seems necessary to monitor the amount of methanol and
      give a warning to watch out for the latent risk problem of methanol uptake, and
      establish a definitive relationship between the degree of intoxication observed
      and the accumulation of methanol in the blood.

PMID- 27023324
TI  - Comparison of Newborn Hearing Screening in Well-Baby Nursery and NICU: A Study
      Applied to Reduce Referral Rate in NICU.
AB  - OBJECTIVES: To determine whether newborn hearing screening in a well-baby nursery
      (WBN) and neonatal intensive care unit (NICU) nursery: 1) meet three targeted,
      screening, referral, and diagnostic follow-up rates; 2) compare the average age
      of diagnosis for infants admitted to the WIN and NICU; and 3) determine
      prevalence of hearing loss in neonatal population; and 4) try to find a practical
      newborn hearing screening time algorithm to reduce refer rate in NICU. MATERIALS
      AND METHODS: It examined 15,624 newborns in the WBN (13,676) and NICU (1948)
      screened for congenital HL using AABR. The variables analyzed in it were the
      screening rate, referral rate, follow-up rate, diagnostic rate and diagnostic
      age, prevalence rate, degrees of congenital bilateral HL. The study was approved
      by the hospital's institutional review board (13MMHISO23). RESULTS: The screening
      rates were 99.8% and 99.6% in the WBN and NICU groups, respectively, without
      significant difference. The referral rates were 0.7% and 2.8% in the WBN and NICU
      groups, with significant difference. Furthermore, the diagnostic follow-up rates
      were 76.7% and 89.1% in the WBN and NICU groups, without significant difference.
      The average initial diagnostic ages were 1.9 months and 3.8 months in the WBN and
      NICU groups, with significant difference. The prevalence of congenital bilateral
      hearing loss were 0.27% and 1.6% in the WBN and NICU groups, with significant
      difference. CONCLUSION: The screening, referral and follow-up rate in the WBN and
      NICU groups were equivalent to the quality indicators. For NICU group, screening
      and diagnostic follow up were performed later than those in WBN group; however
      the lower referral rate in our NICU group was successfully achieved in this study
      and can be applied clinically. The prevalence of congenital bilateral hearing
      loss was higher in the NICU group than in the WBN group.

PMID- 27023325
TI  - International Society of Urological Pathology (ISUP) Grading of Prostate Cancer.

PMID- 27023326
TI  - Acid Is Key to the Radical-Trapping Antioxidant Activity of Nitroxides.
AB  - Persistent dialkylnitroxides (e.g., 2,2,6,6-tetramethylpiperidin-1-oxyl, TEMPO)
      play a central role in the activity of hindered amine light stabilizers (HALS)
      additives that inhibit the (photo)oxidative degradation of consumer and
      industrial products. The accepted mechanism of HALS comprises a catalytic cycle
      involving the rapid combination of a nitroxide with an alkyl radical to yield an
      alkoxyamine that subsequently reacts with a peroxyl radical to eventually re-form
      the nitroxide. Herein, we offer evidence in favor of an alternative reaction
      mechanism involving the acid-catalyzed reaction of a nitroxide with a peroxyl
      radical to yield an oxoammonium ion followed by electron transfer from an alkyl
      radical to the oxoammonium ion to re-form the nitroxide. In preliminary work, we
      showed that TEMPO reacts with peroxyl radicals at diffusion-controlled rates in
      the presence of acids. Now, we show that TEMPO can be regenerated from its
      oxoammonium ion by reaction with alkyl radicals. We have determined that this
      reaction, which has been proposed to be a key step in TEMPO-catalyzed synthetic
      transformations, occurs with k ~ 1-3 * 10(10) M(-1) s(-1), thereby enabling it to
      compete with O2 for alkyl radicals. The addition of weak acids facilitates this
      reaction, whereas the addition of strong acids slows it by enabling back electron
      transfer. The chemistry is shown to occur in hydrocarbon autoxidations at
      elevated temperatures without added acid due to the in situ formation of
      carboxylic acids, accounting for the long-known catalytic radical-trapping
      antioxidant activity of TEMPO that prompted the development of HALS.

PMID- 27023327
TI  - Autobiographical Memory in the Angry Self.
AB  - The impact of anger on autobiographical recall was examined in two studies. In
      Experiment 1, 76 participants differing in trait anger completed an
      autobiographical memory task (AMT). In Experiment 2, 50 participants with
      elevated trait anger were either provoked or not provoked and subsequently
      completed an AMT. Across both studies, participants with high dispositional anger
      reported more anger-related memories, describing themselves as the primary agent
      of anger. In Experiment 2, provoked participants reported more memories
      describing themselves as the target of anger. These findings highlight the
      distinct patterns of memory recall associated with trait versus state anger.
      Findings are discussed in terms of retrieval biases operating in angry
      individuals and proposals stemming from self-memory system models of
      autobiographical memory. 

PMID- 27023328
TI  - Pyrexia in dabrafenib-treated melanoma patients is not associated with common
      genetic variation or HLA polymorphisms.
AB  - AIM: Pyrexia is a common adverse event (AE) on dabrafenib treatment (monotherapy
      or combination with trametinib). Since germline SNPs and HLA alleles are
      implicated in drug-induced AEs, this study investigated their association with
      pyrexia. PATIENTS & METHODS: 1006 melanoma subjects from five dabrafenib
      trametinib clinical studies underwent genotyping for genome-wide SNPs, which
      enabled imputation of 150 HLA alleles. SNP/HLA allele frequencies were compared
      between pyrexia cases (n = 218) and controls (n = 361) out of the 1006 subjects
      by meta-analysis. RESULTS: This analysis had adequate power to detect association
      of common SNPs or HLA alleles with moderate to large effects on pyrexia (odds
      ratio >6), but no significant association was found. CONCLUSION: The study
      suggests that common genetic variation or HLA polymorphisms do not contribute
      substantially to dabrafenib-induced pyrexia.

PMID- 27023329
TI  - Self-Complementary Adeno-Associated Virus Vectors Improve Transduction Efficiency
      of Corneal Endothelial Cells.
AB  - Transplantation of a donor cornea to restore vision is the most frequently
      performed transplantation in the world. Corneal endothelial cells (CEC) are
      crucial for the outcome of a graft as they maintain corneal transparency and
      avoid graft failure due to corneal opaqueness. Given the characteristic of being
      a monolayer and in direct contact with culture medium during cultivation in eye
      banks, CEC are specifically suitable for gene therapeutic approaches prior to
      transplantation. Recombinant adeno-associated virus 2 (rAAV2) vectors represent a
      promising tool for gene therapy of CEC. However, high vector titers are needed to
      achieve sufficient gene expression. One of the rate-limiting steps for transgene
      expression is the conversion of single-stranded (ss-) DNA vector genome into
      double-stranded (ds-) DNA. This step can be bypassed by using self-complementary
      (sc-) AAV2 vectors. Aim of this study was to compare for the first time
      transduction efficiencies of ss- and scAAV2 vectors in CEC. For this purpose AAV2
      vectors containing enhanced green fluorescent protein (GFP) as transgene were
      used. Both in CEC and in donor corneas, transduction with scAAV2 resulted in
      significantly higher transgene expression compared to ssAAV2. The difference in
      transduction efficiency decreased with increasing vector titer. In most cases,
      only half the vector titer of scAAV2 was required for equal or higher gene
      expression rates than those of ssAAV2. In human donor corneas, GFP expression was
      64.7+/-11.3% (scAAV) and 38.0+/-8.6% (ssAAV) (p<0.001), respectively.
      Furthermore, transduced cells maintained their viability and showed regular
      morphology. Working together with regulatory authorities, a translation of AAV2
      vector-mediated gene therapy to achieve a temporary protection of corneal
      allografts during cultivation and transplantation could therefore become more
      realistic. 

PMID- 27023330
TI  - Role of the Substrate Specificity-Defining Residues of Human SIRT5 in Modulating
      the Structural Stability and Inhibitory Features of the Enzyme.
AB  - Sirtuins are emerging as the key regulators of metabolism and aging, and their
      potential activators and inhibitors are being explored as therapeutics for
      improving health and treating associated diseases. Despite the global structural
      similarity among all seven isoforms of sirtuins (of which most of them catalyze
      the deacetylation reaction), SIRT5 is the only isoform that catalyzes the
      cleavage of negatively charged acylated substrates, and the latter feature
      appears to be encoded by the presence of Tyr102 and Arg105 residues at the active
      site pocket of the enzyme. To determine the contributions of the above residues
      in SIRT5 (vis a vis the corresponding residues of SIRT1) on substrate
      selectivity, inhibition by EX527 and nicotinamide, secondary structural features
      and thermal stability of the enzymes, we created single and double mutations
      (viz. Y102A, R105l, and Y102A/R105I) in SIRT5. The kinetic data revealed that
      while Y102A mutant enzyme catalyzed both deacetylation and desuccinylation
      reactions with comparable efficiencies, R105I and Y102A/R105I mutant enzymes
      favored the deacetylase reaction. Like SIRT1, the nicotinamide inhibition of
      SIRT5 double mutant (Y102A/R105I) exhibited the mixed non-competitive behavior.
      On the other hand, the desuccinylation reaction of both wild-type and Y102A
      mutant enzymes conformed to the competitive inhibition model. The inhibitory
      potency of EX527 progressively increased from Y102A, R105I, to Y102A/R105 mutant
      enzymes in SIRT5, but it did not reach to the level obtained with SIRT1. The CD
      spectroscopic data for the wild-type and mutant enzymes revealed changes in the
      secondary structural features of the enzymes, and such changes were more
      pronounced on examining their thermal denaturation patterns. A cumulative account
      of our experimental data reveal mutual cooperation between Y102 and R105 residues
      in promoting the desuccinylation versus deacetylation reaction in SIRT5, and the
      overall catalytic feature of the enzyme is manifested via the mutation induced
      modulation in the protein structure. 

PMID- 27023331
TI  - Anti-bacterial and anti-inflammatory effects of ethanol extract from Houttuynia
      cordata poultice.
AB  - Houttuynia cordata (HC) has been commonly used as many traditional remedies in
      local areas of Japan. Although many pharmacological activities of HC have been
      reported, the mechanism underlying the effect of HC remains unknown. We conducted
      the interview survey in Japan to verify how HC was actually used. The interview
      survey revealed that HC poultice (HCP) prepared from smothering fresh leaves of
      HC was most frequently used for the treatment of purulent skin diseases including
      furuncle and carbuncle with high effectiveness. Ethanol extract of HCP (eHCP)
      showed anti-bacterial effects against methicillin-resistant Staphylococcus aureus
      (MRSA), and showed an anti-biofilm activity against MRSA. eHCP showed dose
      dependent inhibition of S. aureus lipoteichoic acid (LTA)-induced interleukin-8
      and CCL20 production in human keratinocyte without any cytotoxicity. These
      results suggest that HCP is effective for skin abscess and its underlying
      mechanism might be the complicated multiple activities for both bacteria and host
      cells. 

PMID- 27023332
TI  - Opioids increase hip fracture risk: a meta-analysis.
AB  - The relationship between hip fracture risk and opioid use remains controversial.
      Thus, we performed a meta-analysis to assess the risk of hip fracture among
      opioid users. PubMed and EMBASE were searched for studies published from the
      inception of the databases until June 2015. The information was extracted
      independently by two teams of authors. When the heterogeneity was significant,
      the random-effects model was used to calculate the overall pooled risk estimates.
      Ten studies with 697,011 patients were included in the final meta-analysis. The
      overall combined relative risk for the use of opioids and hip fracture was 1.54
      [95 % confidence interval (CI) 1.34-1.77]. Subgroup analyses revealed sources of
      heterogeneity, and sensitivity analysis indicated stable results, and no
      publication bias was observed. This meta-analysis demonstrates that opioids
      significantly increase the risk of hip fracture.

PMID- 27023333
TI  - Thyroid function and autoimmunity are associated with the risk of vertebral
      fractures in postmenopausal women.
AB  - Overt or subclinical thyroid dysfunction may affect the risk of fragility
      fractures. The aim of the present study was to assess the association of thyroid
      function and autoimmunity with vertebral fractures (VF) in a large sample of
      Greek postmenopausal women. This cross-sectional study recruited 335 euthyroid
      postmenopausal women, aged 35-79 years. Euthyroidism was verified by serum
      thyroid-stimulating hormone (TSH) within the laboratory reference range (0.4-4.5
      MUIU/mL). VFs were diagnosed by lumbar spine lateral radiographs, according to
      quantitative procedures. Serum free triiodothyronine (FT3), free thyroxine (FT4),
      TSH, as well as levels of anti-thyroglobulin (anti-TG) and thyroid peroxidase
      antibodies (anti-TPO) were compared according to the presence of VFs.
      Multivariate logistic regression showed that the presence of VFs was predicted
      independently by ln-TSH levels (OR = 0.290, p = 0.037) and positive anti-TG
      antibodies (OR = 3.308, p = 0.026) in models adjusted for age, menopausal age,
      and ln-HOMA-IR. Stepwise logistic regression analysis showed that the presence of
      VFs was predicted by menopausal age (OR = 1.120, p = 0.001), ln-TSH (OR = 0.312,
      p = 0.052), and thyroid autoimmunity (anti-TG and anti-TPO positive: OR = 6.637,
      p = 0.007) in a model that also included age and ln-HOMA-IR. Women with lower
      circulating TSH had higher risk of having a VF, independently of age, menopausal
      age, and insulin resistance. The presence of positive anti-TG/anti-TPO antibodies
      also indicated an elevated risk of fracture. Levels of thyroid hormones had no
      apparent effect on the risk of fracture. Further studies are necessary to
      establish the significance of our findings.

PMID- 27023334
TI  - Assessing PM2.5 Exposures with High Spatiotemporal Resolution across the
      Continental United States.
AB  - A number of models have been developed to estimate PM2.5 exposure, including
      satellite-based aerosol optical depth (AOD) models, land-use regression, or
      chemical transport model simulation, all with both strengths and weaknesses.
      Variables like normalized difference vegetation index (NDVI), surface
      reflectance, absorbing aerosol index, and meteoroidal fields are also informative
      about PM2.5 concentrations. Our objective is to establish a hybrid model which
      incorporates multiple approaches and input variables to improve model
      performance. To account for complex atmospheric mechanisms, we used a neural
      network for its capacity to model nonlinearity and interactions. We used
      convolutional layers, which aggregate neighboring information, into a neural
      network to account for spatial and temporal autocorrelation. We trained the
      neural network for the continental United States from 2000 to 2012 and tested it
      with left out monitors. Ten-fold cross-validation revealed a good model
      performance with a total R(2) of 0.84 on the left out monitors. Regional R(2)
      could be even higher for the Eastern and Central United States. Model performance
      was still good at low PM2.5 concentrations. Then, we used the trained neural
      network to make daily predictions of PM2.5 at 1 km * 1 km grid cells. This model
      allows epidemiologists to access PM2.5 exposure in both the short-term and the
      long-term.

PMID- 27023335
TI  - The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke
      Prevention in Patients with Atrial Fibrillation.
AB  - Anticoagulation is important in stroke prevention in patients with atrial
      fibrillation. Until recently, heparins and vitamin K antagonists were the only
      available therapy for stroke reduction in atrial fibrillation (AF) patients. Non
      vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin
      inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and
      edoxaban) are now available and offer new options for stroke prevention. This
      article reviews the available data on the use of NOACs for primary and secondary
      stroke prevention in AF patients and describes specific patient populations to
      guide clinician in making the informed decision regarding appropriate use of
      those agents. It also addresses the use of NOACs early after acute stroke and use
      of thrombolysis while on NOAC. 

PMID- 27023340
TI  - Long-Chain Aliphatic Polymers To Bridge the Gap between Semicrystalline
      Polyolefins and Traditional Polycondensates.
AB  - Other than their established short-chain congeners, polycondensates based on long
      chain difunctional monomers are often dominated by the long methylene sequences
      of the repeat units in their solid-state structures and properties. This places
      them between traditional polycondensates and polyethylenes. The availability of
      long-chain monomers as a key prerequisite has benefited much from advances in the
      catalytic conversion of plant oils, via biotechnological and purely chemical
      approaches, likewise. This has promoted studies of, among others, applications
      relevant properties. A comprehensive account is given of long-chain monomer
      syntheses and the preparation and physical properties, morphologies, mechanical
      behavior, and degradability of long-chain polyester, polyamides, polyurethanes,
      polyureas, polyacetals, and polycarbonates. 

PMID- 27023336
TI  - Identifying Patients with Bacteremia in Community-Hospital Emergency Rooms: A
      Retrospective Cohort Study.
AB  - OBJECTIVES: (1) To develop a clinical prediction rule to identify patients with
      bacteremia, using only information that is readily available in the emergency
      room (ER) of community hospitals, and (2) to test the validity of that rule with
      a separate, independent set of data. DESIGN: Multicenter retrospective cohort
      study. SETTING: To derive the clinical prediction rule we used data from 3
      community hospitals in Japan (derivation). We tested the rule using data from one
      other community hospital (validation), which was not among the three "derivation"
      hospitals. PARTICIPANTS: Adults (age >= 16 years old) who had undergone blood
      culture testing while in the ER between April 2011 and March 2012. For the
      derivation data, n = 1515 (randomly sampled from 7026 patients), and for the
      validation data n = 467 (from 823 patients). ANALYSIS: We analyzed 28 candidate
      predictors of bacteremia, including demographic data, signs and symptoms,
      comorbid conditions, and basic laboratory data. Chi-square tests and multiple
      logistic regression were used to derive an integer risk score (the "ID-BactER"
      score). Sensitivity, specificity, likelihood ratios, and the area under the
      receiver operating characteristic curve (i.e., the AUC) were computed. RESULTS:
      There were 241 cases of bacteremia in the derivation data. Eleven candidate
      predictors were used in the ID-BactER score: age, chills, vomiting, mental
      status, temperature, systolic blood pressure, abdominal sign, white blood-cell
      count, platelets, blood urea nitrogen, and C-reactive protein. The AUCs was 0.80
      (derivation) and 0.74 (validation). For ID-BactER scores >= 2, the sensitivities
      for derivation and validation data were 98% and 97%, and specificities were 20%
      and 14%, respectively. CONCLUSIONS: The ID-BactER score can be computed from
      information that is readily available in the ERs of community hospitals. Future
      studies should focus on developing a score with a higher specificity while
      maintaining the desired sensitivity.

PMID- 27023341
TI  - Parkinsonism and cognitive impairment due to a giant frontal arachnoid cyst and
      improving after shunting.

PMID- 27023343
TI  - Optical Coherence Tomography Angiography of Choroidal Neovascularization
      Secondary to Pathologic Myopia.
AB  - PURPOSE: To analyze the ability of optical coherence tomography angiography (OCT
      A) to detect the presence of myopic choroidal neovascularization (CNV) and to
      describe structural features of myopic CNV on OCT-A. METHODS: Patients with CNV
      secondary to high myopia (>6 diopters and >26 mm axial length) underwent
      multimodal imaging, including multicolor imaging, fluorescein angiography,
      spectral-domain (SD)-OCT and OCT-A. The OCT-A features of CNV were analyzed and
      correlated with the angiography and SD-OCT findings. RESULTS: On OCTA, the CNV
      appeared as a large hyperintense vascular anastomotic network at the edge of the
      lesion. On the basis of the OCT-A images and reports in the literature, we
      propose the following two terms for describing myopic CNV characteristics:
      'interlacing' and 'tangled' vascular networks. CONCLUSION: OCT-A is a very useful
      tool for the diagnosis and evaluation of CNV complicating high myopia; however,
      it does not appear to be sufficient when used alone and should be considered for
      use in combination with SD-OCT and conventional angiography.

PMID- 27023342
TI  - The Effect of Pericellular Oxygen Levels on Proteomic Profile and Lipogenesis in
      3T3-L1 Differentiated Preadipocytes Cultured on Gas-Permeable Cultureware.
AB  - Pericellular oxygen concentration represents an important factor in the
      regulation of cell functions, including cell differentiation, growth and
      mitochondrial energy metabolism. Hypoxia in adipose tissue has been associated
      with altered adipokine secretion profile and suggested as a possible factor in
      the development of type 2 diabetes. In vitro experiments provide an indispensable
      tool in metabolic research, however, physical laws of gas diffusion make
      prolonged exposure of adherent cells to desired pericellular O2 concentrations
      questionable. The aim of this study was to investigate the direct effect of
      various O2 levels (1%, 4% and 20% O2) on the proteomic profile and triglyceride
      accumulation in 3T3-L1 differentiated preadipocytes using gas-permeable
      cultureware. Following differentiation of cells under desired pericellular O2
      concentrations, cell lysates were subjected to two-dimensional gel
      electrophoresis and protein visualization using Coomassie blue staining. Spots
      showing differential expression under hypoxia were analyzed using matrix-assisted
      laser desorption/ionization mass spectrometry. All identified proteins were
      subjected to pathway analysis. We observed that protein expression of 26 spots
      was reproducibly affected by 4% and 1% O2 (17 upregulated and 9 downregulated).
      Pathway analysis showed that mitochondrial energy metabolism and triglyceride
      synthesis were significantly upregulated by hypoxia. In conclusion, this study
      demonstrated the direct effects of pericellular O2 levels on adipocyte energy
      metabolism and triglyceride synthesis, probably mediated through the reversed
      tricarboxylic acid cycle flux. 

PMID- 27023344
TI  - Hair cortisol levels, perceived stress and body mass index in women and children
      living in socioeconomically disadvantaged neighborhoods: the READI study.
AB  - Disadvantaged communities provide adverse psychosocial exposures that have been
      linked to high levels of stress, and this may provide one explanatory pathway
      linking socioeconomic disadvantage to obesity. This study used hair cortisol
      analysis to quantify associations between stress and body mass index (BMI), and
      between hair cortisol and perceived psychological stress levels, in women and
      children living in socioeconomically disadvantaged neighborhoods. Participants
      were a volunteer sample of 70 women from the Resilience for Eating and Activity
      Despite Inequality study, including 30 maternal-child pairs. Women self-reported
      body weight, height and perceived psychological stress using the Perceived Stress
      Scale (PSS), and provided hair samples for themselves and their child. Children's
      body weight and height were measured. Following extraction, hair cortisol levels
      were measured using enzyme-linked immunosorbent assay. Multiple linear regression
      models examined associations between stress and BMI, and between hair cortisol
      and perceived stress levels in women and children. Women's hair cortisol levels
      were not associated with their BMI or PSS scores. Women's PSS scores were
      positively associated with their BMI (p = 0.015). Within maternal-child pairs,
      mothers and children's hair cortisol levels were strongly positively associated
      (p = 0.006). Maternal hair cortisol levels and PSS scores were unrelated to their
      child's zBMI. Children's hair cortisol levels were not associated with their zBMI
      or with their mother's PSS score. Findings suggest that cortisol-based and
      perceived psychological measures of stress may be distinct among women and
      children living in disadvantaged neighborhoods. Perceived psychological measures
      may be more important predictors of weight-related risk. 

PMID- 27023345
TI  - Influence of antenatal physical exercise on heart rate variability and QT
      variability.
AB  - OBJECTIVE: We sought to characterise the influence of an antenatal exercise
      programme on ECG-derived cardiac variables. METHODS: Fifity-one healthy pregnant
      women were recruited and randomly assigned (2 * 2*2 design) to an exercise group
      or a control group. Exercising groups attended weekly classes from the 20th week
      of pregnancy onwards. Cardiovascular assessments (heart rate variabiliy (HRV),
      QT, and the QT variability index (QTVI)) were performed at 12-16, 26-28, 34-36
      weeks and 12 weeks following birth, during supine rest and exercise conditions.
      RESULTS: Advancing gestation was associated with an increased maternal heart rate
      (p = 0.001), shorter QT interval (p = 0.003), diminished HRV (p = 0.002) and
      increased QTVI (p = 0.002). Each of these changes was reversed within 12 weeks
      postpartum (p < 0.004). The Exercise group displayed exaggerated changes for all
      variables (except QT) but only during supine rest in the third trimester (p <
      0.029). CONCLUSION: Advancing gestation is associated with a shift in HRV/QTVI
      towards values that have been associated with an elevated risk of arrhythmia. A
      20-week exercise programme undertaken between mid and late pregnancy exaggerated
      these changes during rest in the third trimester of pregnancy.

PMID- 27023346
TI  - Circumferential anorectal leiomyomatosis.

PMID- 27023347
TI  - Pushing the boundaries of the management of uncomplicated diverticulitis.

PMID- 27023348
TI  - Comments to 'Rubber band ligation versus excisional haemorrhoidectomy for
      haemorrhoids'.
AB  - OBJECTIVE: To review the efficacy and safety of the two most popular conventional
      methods of haemorrhoidal treatment, rubber band ligation and excisional
      haemorrhoidectomy (EH). The original study has now been updated using the same
      search strategy. SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL, and CINAHL
      up to October 2010. SELECTION CRITERIA: Randomised controlled trials comparing
      rubber band ligation with EH for symptomatic haemorrhoids in adult human patients
      were included. DATA COLLECTION AND ANALYSIS: We extracted data on to a previously
      designed data extraction sheet. Dichotomous data were presented as relative risk
      and 95 % confidence intervals, and continuous outcomes as weighted mean
      difference and 95 % confidence intervals. MAIN RESULTS: Three trials (of poor
      methodological quality) met the inclusion criteria. Complete remission of
      haemorrhoidal symptom was better with EH (three studies, 202 patients, RR 1.68,
      95 % CI 1.00-2.83). There was a significant heterogeneity between the studies (I2
      = 90.5 %; P = 0.0001). Similar analysis based on the grading of haemorrhoids
      revealed the superiority of EH over RBL for grade III haemorrhoids (prolapse that
      needs manual reduction) (two trials, 116 patients, RR 1.23, CI 1.04-1.45; P =
      0.01). However, no significant difference was noticed in grade II haemorrhoids
      (prolapse that reduces spontaneously on cessation of straining) (one trial, 32
      patients, RR 1.07, CI 0.94-1.21; P = 0.32). Fewer patients required re-treatment
      after EH (three trials, RR 0.20, CI 0.09-0.40; P < 0.00001). Patients undergoing
      EH were at significantly higher risk of post-operative pain (three trials, fixed
      effect; 212 patients, RR 1.94, 95 % CI 1.62-2.33, P < 0.00001) and of delayed
      complications (three trials, 204 patients, RR 6.32, CI 1.15-34.89; P = 0.03).
      AUTHORS' CONCLUSIONS: The present systematic review confirms the long-term
      efficacy of EH, at least for grade III haemorrhoids, compared to the less
      invasive technique of RBL but at the expense of increased pain, higher
      complications and more time off work. However, despite these disadvantages of EH,
      patient satisfaction and patient's acceptance of the treatment modalities seem to
      be similar following both the techniques implying patient's preference for
      complete long-term cure of symptoms and possibly less concern for minor
      complications. So, RBL can be adopted as the choice of treatment for grade II
      haemorrhoids with similar results but without the side effects of EH while
      reserving EH for grade III haemorrhoids or recurrence after RBL. More robust
      study is required to make definitive conclusions.

PMID- 27023349
TI  - The agonist-specific voltage dependence of M2 muscarinic receptors modulates the
      deactivation of the acetylcholine-gated K(+) current (I KACh).
AB  - Recently, it has been shown that G protein-coupled receptors (GPCRs) display
      intrinsic voltage sensitivity. We reported that the voltage sensitivity of M2
      muscarinic receptor (M2R) is also ligand specific. Here, we provide additional
      evidence to understand the mechanism underlying the ligand-specific voltage
      sensitivity of the M2R. Using ACh, pilocarpine (Pilo), and bethanechol (Beth), we
      evaluated the agonist-specific effects of voltage by measuring the ACh-activated
      K(+) current (I KACh) in feline and rabbit atrial myocytes and in HEK-293 cells
      expressing M2R-Kir3.1/Kir3.4. The activation of I KACh by the muscarinic agonist
      Beth was voltage insensitive, suggesting that the voltage-induced conformational
      changes in M2R do not modify its affinity for this agonist. Moreover,
      deactivation of the Beth-evoked I KACh was voltage insensitive. By contrast,
      deactivation of the ACh-induced I KACh was significantly slower at -100 mV than
      at +50 mV, while an opposite effect was observed when I KACh was activated by
      Pilo. These findings are consistent with the voltage affinity pattern observed
      for these three agonists. Our findings suggest that independent of how voltage
      disturbs the receptor binding site, the voltage dependence of the signaling
      pathway is ultimately determined by the agonist. These observations emphasize the
      pharmacological potential to regulate the M2R-parasympathetic associated cardiac
      function and also other cellular signaling pathways by exploiting the voltage
      dependent properties of GPCRs.

PMID- 27023350
TI  - Piezo1-dependent regulation of urinary osmolarity.
AB  - The collecting duct (CD) is the final segment of the kidney involved in the fine
      regulation of osmotic and ionic balance. During dehydration, arginine vasopressin
      (AVP) stimulates the expression and trafficking of aquaporin 2 (AQP2) to the
      apical membrane of CD principal cells, thereby allowing water reabsorption from
      the primary urine. Conversely, when the secretion of AVP is lowered, as for
      instance upon water ingestion or as a consequence of diabetes insipidus, the CD
      remains water impermeable leading to enhanced diuresis and urine dilution. In
      addition, an AVP-independent mechanism of urine dilution is also at play when
      fasting. Piezo1/2 are recently discovered essential components of the non
      selective mechanically activated cationic channels. Using quantitative PCR
      analysis and taking advantage of a beta-galactosidase reporter mouse, we
      demonstrate that Piezo1 is preferentially expressed in CD principal cells of the
      inner medulla at the adult stage, unlike Piezo2. Remarkably, siRNAs knock-down or
      conditional genetic deletion of Piezo1 specifically in renal cells fully
      suppresses activity of the stretch-activated non-selective cationic channels
      (SACs). Piezo1 in CD cells is dispensable for urine concentration upon
      dehydration. However, urinary dilution and decrease in urea concentration
      following rehydration are both significantly delayed in the absence of Piezo1.
      Moreover, decreases in urine osmolarity and urea concentration associated with
      fasting are fully impaired upon Piezo1 deletion in CD cells. Altogether, these
      findings indicate that Piezo1 is critically required for SAC activity in CD
      principal cells and is implicated in urinary osmoregulation.

PMID- 27023351
TI  - Smooth muscle filamin A is a major determinant of conduit artery structure and
      function at the adult stage.
AB  - Human mutations in the X-linked FLNA gene are associated with a remarkably
      diverse phenotype, including severe arterial morphological anomalies. However,
      the role for filamin A (FlnA) in vascular cells remains partially understood. We
      used a smooth muscle (sm)-specific conditional mouse model to delete FlnA at the
      adult stage, thus avoiding the developmental effects of the knock-out.
      Inactivation of smFlnA in adult mice significantly lowered blood pressure,
      together with a decrease in pulse pressure. However, both the aorta and carotid
      arteries showed a major outward hypertrophic remodeling, resistant to losartan,
      and normally occurring in hypertensive conditions. Notably, arterial compliance
      was significantly enhanced in the absence of smFlnA. Moreover, reactivity of
      thoracic aorta rings to a variety of vasoconstrictors was elevated, while basal
      contractility in response to KCl depolarization was reduced. Enhanced reactivity
      to the thromboxane A2 receptor agonist U46619 was fully reversed by the ROCK
      inhibitor Y27632. We discuss the possibility that a reduction in arterial
      stiffness upon smFlnA inactivation might cause a compensatory increase in conduit
      artery diameter for normalization of parietal tension, independently of the ROCK
      pathway. In conclusion, deletion of smFlnA in adult mice recapitulates the
      vascular phenotype of human bilateral periventricular nodular heterotopia,
      culminating in aortic dilatation.

PMID- 27023352
TI  - Endostatin is protective against monocrotaline-induced right heart disease
      through the inhibition of T-type Ca(2+) channel.
AB  - Endostatin (ES), a C-terminal fragment of collagen XVIIIalpha1, has a potent anti
      angiogenic effect. ES prevents tumor proliferation through inhibiting T-type
      Ca(2+) channel. T-type Ca(2+) channel is re-expressed during heart diseases
      including monocrotaline (MCT)-induced right heart failure. The present study
      aimed to clarify the effects of ES on T-type Ca(2+) channel and pathogenesis of
      MCT-induced right ventricular disease. MCT or saline was injected
      intraperitoneally to rats. After cardiomyocytes were isolated from right
      ventricles (RVs), T-type Ca(2+) channel current (I CaT) was measured by a patch
      clamp method. After ES small interfering RNA (siRNA) or control siRNA (20 MUg)
      was administrated for 1 week via the right jugular vein 1 week after MCT
      injection, echocardiography and histological analysis were done. I CaT was
      significantly increased in RV from MCT-injected rats, and ES significantly
      inhibited it. The survival rate of ES siRNA-administrated MCT rats (MCT ES si
      group) was decreased. In echocardiography, although ES siRNA did not affect
      pulmonary arterial pressure, RV systolic function was impaired in MCT ES si group
      compared with control siRNA-administrated MCT rats (MCT cont si group). In the
      histological analysis of RV, ES expression was increased in MCT cont si group,
      and ES siRNA inhibited it. Furthermore, although MCT cont si group showed only
      cardiomyocyte hypertrophy, MCT ES si group showed notable enlargement of
      intercellular spaces. The present study for the first time revealed that ES
      inhibits T-type Ca(2+) channel activity in RV from MCT-injected rats. ES gene
      knockdown deteriorates MCT-induced right heart disease. ES is thus
      cardioprotective possibly through inhibiting T-type Ca(2+) channel activity.

PMID- 27023354
TI  - In situ fabrication and investigation of nanostructures and nanodevices with a
      microscope.
AB  - The widespread availability of nanostructures and nanodevices has placed strict
      requirements on their comprehensive characterization. Herein, in situ techniques
      are demonstrated to have created a rare opportunity to accurately analyze the
      intrinsic properties of individual nanostructures and to accomplish the smart
      design of nanodevices made from these nanostructures. This paper reviews recent
      developments in in situ fabrication and characterization technologies established
      within various types of microscopes and the rich information they may provide.
      The in situ techniques are shown to be important for exploration of many
      intriguing phenomena at the nanoscale which may then be followed by the smart
      integration of nanostructures into real functional devices. Successful in situ
      detection results are presented and discussed, especially in the areas of energy
      generation, biological imaging and water pumping. Finally, we conclude this
      article with an examination of the existing challenges and the outlook for this
      quickly emerging field.

PMID- 27023353
TI  - Assessment of Blood Contamination in Biological Fluids Using MALDI-TOF MS.
AB  - Biological fluid sample collection often includes the risk of blood contamination
      that may alter the proteomic profile of biological fluid. In proteomics studies,
      exclusion of contaminated samples is usually based on visual inspection and
      counting of red blood cells in the sample; analysis of specific blood derived
      proteins is less used. To fill the gap, we developed a fast and sensitive method
      for ascertainment of blood contamination in crude biological fluids, based on
      specific blood-derived protein, hemoglobin detection by MALDI-TOF MS. The MALDI
      TOF MS based method allows detection of trace hemoglobin with the detection limit
      of 0.12 nM. UV-spectrometry, which was used as reference method, was found to be
      less sensitive. The main advantages of the presented method are that it is fast,
      effective, sensitive, requires very small sample amount and can be applied for
      detection of blood contamination in various biological fluids collected for
      proteomics studies. Method applicability was tested on human cerebrospinal and
      follicular fluid, which proteomes generally do not contain hemoglobin, however,
      which possess high risk for blood contamination. Present method successfully
      detected the blood contamination in 12 % of cerebrospinal fluid and 24 % of
      follicular fluid samples. High percentage of contaminated samples accentuates the
      need for initial inspection of proteomic samples to avoid incorrect results from
      blood proteome overlap.

PMID- 27023355
TI  - Additive opportunistic capture explains group hunting benefits in African wild
      dogs.
AB  - African wild dogs (Lycaon pictus) are described as highly collaborative endurance
      pursuit hunters based on observations derived primarily from the grass plains of
      East Africa. However, the remaining population of this endangered species mainly
      occupies mixed woodland savannah where hunting strategies appear to differ from
      those previously described. We used high-resolution GPS and inertial technology
      to record fine-scale movement of all members of a single pack of six adult
      African wild dogs in northern Botswana. The dogs used multiple short-distance
      hunting attempts with a low individual kill rate (15.5%), but high group feeding
      rate due to the sharing of prey. Use of high-level cooperative chase strategies
      (coordination and collaboration) was not recorded. In the mixed woodland habitats
      typical of their current range, simultaneous, opportunistic, short-distance
      chasing by dogs pursuing multiple prey (rather than long collaborative pursuits
      of single prey by multiple individuals) could be the key to their relative
      success in these habitats. 

PMID- 27023356
TI  - PEGylation of cytochrome c at the level of lysine residues mediated by a
      microbial transglutaminase.
AB  - OBJECTIVES: To establish a method for microbial transglutaminase (mTG)-mediated
      PEGylation of proteins at the level of lysine (Lys) residues. RESULTS:
      Carboxybenzyl-glutaminyl-glycinyl-methoxypolyethylene glycol (CBZ-QG-mPEG) was
      prepared by introducing carboxybenzyl-glutaminyl-glycine (CBZ-QG) to mPEG amine.
      The analysis by Fourier transform infrared spectroscopy and SDS-PAGE showed that
      CBZ-QG-mPEG was successfully synthesized and can be recognized by mTG as an acyl
      donor to modify therapeutic protein, cytochrome c (cyt c). Finally, under an
      optimized condition (cyt c 0.5 mg/ml, CBZ-QG-mPEG 11.25 mg/ml, mTG 0.5 mg/ml, 37 
      degrees C, 2 h), the PEGylation yield reached 76.5 %. CONCLUSIONS: This is the
      first study regarding the PEGylation of protein at the level of Lys residues
      catalyzed by mTG. The novel method could be employed to immobilize active
      proteins and modify therapeutic proteins.

PMID- 27023357
TI  - The God Allusion : Individual Variation in Agency Detection, Mentalizing and
      Schizotypy and Their Association with Religious Beliefs and Behaviors.
AB  - It has previously been suggested that the historically and geographically
      widespread persistence of religious beliefs occurs because it is a by-product of
      normal cognitive processes, ones which first evolved to confer survival
      advantages in the social domain. If this theory holds, then it is likely that
      inter-individual variation in the same biases may predict corresponding variation
      in religious thoughts and behaviors. Using an online questionnaire, 298
      participants answered questions regarding their tendency to detect agency, the
      degree to which they displayed schizotypal traits, their ability to understand
      the emotions and motivations of others ("mentalizing"), and their religious
      beliefs and behaviors. Path analysis suggests that mentalizing, agency detection,
      and schizotypal thinking were each independently related to religiosity.
      Furthermore, schizotypal thinking and agency detection were highly interrelated
      with one another, whereas mentalizing was not. Although the degree to which an
      individual engages with religious or spiritual beliefs will be influenced by
      their cultural and historical context, this paper helps to elucidate the
      interplay between various cognitive processes that might predispose some
      individuals but not others toward holding such beliefs in the first place. 

PMID- 27023361
TI  - Financial Disclosure Information Inadvertently Omitted by the Journal in the
      Editorial by Sattar and McInnes (Arthritis Rheumatol, March 2016).

PMID- 27023359
TI  - Brief Report: Menopause and Primary Ovarian Insufficiency in Women Treated for
      Antineutrophil Cytoplasmic Antibody-Associated Vasculitides.
AB  - OBJECTIVE: One of the side effects of cyclophosphamide is earlier menopause and
      primary ovarian insufficiency. This study was undertaken to investigate the onset
      of menopause and the incidence of primary ovarian insufficiency in women with
      antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially after
      treatment with orally administered cyclophosphamide. METHODS: We retrospectively
      studied the onset of menopause and the influence of cyclophosphamide in women
      diagnosed as having AAV in our center between 1970 and 2012. RESULTS: Ninety-four
      premenopausal women diagnosed as having AAV were included. Sixty-seven patients
      received cyclophosphamide, and 27 received other, mostly immunosuppressive,
      medication. Forty-six cyclophosphamide-treated women developed menopause, 22 of
      whom were considered to have primary ovarian insufficiency. None of the patients
      who were not treated with cyclophosphamide developed primary ovarian
      insufficiency. There was a significant association between a cumulative
      cyclophosphamide dose of >16.6 gm, versus a cumulative dose of <16.6 gm, and
      menopause (chi(2)  = 8.72, P = 0.003; odds ratio [OR] 2.60 [95% confidence
      interval 1.38-4.90]). In addition, there was a significant association between a
      cumulative cyclophosphamide dose of <16.6 gm, versus no cyclophosphamide
      exposure, and menopause (chi(2)  = 16.37, P < 0.001; OR 7.32 [95% confidence
      interval 2.79-19.20]). Both women who received cyclophosphamide and those who did
      not experienced involuntary childlessness. CONCLUSION: Earlier menopause and
      primary ovarian insufficiency frequently develop after oral cyclophosphamide
      therapy in premenopausal women with AAV. Involuntary childlessness is common
      after the development of primary ovarian insufficiency, but it also occurs in
      women not treated with cyclophosphamide. These findings emphasize the importance
      of the use of drugs that are not toxic to gonadal function in women of
      childbearing age.

PMID- 27023358
TI  - Long Intergenic Noncoding RNAs Mediate the Human Chondrocyte Inflammatory
      Response and Are Differentially Expressed in Osteoarthritis Cartilage.
AB  - OBJECTIVE: To identify long noncoding RNAs (lncRNAs), including long intergenic
      noncoding RNAs (lincRNAs), antisense RNAs, and pseudogenes, associated with the
      inflammatory response in human primary osteoarthritis (OA) chondrocytes and to
      explore their expression and function in OA. METHODS: OA cartilage was obtained
      from patients with hip or knee OA following joint replacement surgery. Non-OA
      cartilage was obtained from postmortem donors and patients with fracture of the
      neck of the femur. Primary OA chondrocytes were isolated by collagenase
      digestion. LncRNA expression analysis was performed by RNA sequencing (RNAseq)
      and quantitative reverse transcriptase-polymerase chain reaction. Modulation of
      lncRNA chondrocyte expression was achieved using LNA longRNA GapmeRs (Exiqon).
      Cytokine production was measured with Luminex. RESULTS: RNAseq identified 983
      lncRNAs in primary human hip OA chondrocytes, 183 of which had not previously
      been identified. Following interleukin-1beta (IL-1beta) stimulation, we
      identified 125 lincRNAs that were differentially expressed. The lincRNA p50
      associated cyclooxygenase 2-extragenic RNA (PACER) and 2 novel chondrocyte
      inflammation-associated lincRNAs (CILinc01 and CILinc02) were differentially
      expressed in both knee and hip OA cartilage compared to non-OA cartilage. In
      primary OA chondrocytes, these lincRNAs were rapidly and transiently induced in
      response to multiple proinflammatory cytokines. Knockdown of CILinc01 and
      CILinc02 expression in human chondrocytes significantly enhanced the IL-1
      stimulated secretion of proinflammatory cytokines. CONCLUSION: The inflammatory
      response in human OA chondrocytes is associated with widespread changes in the
      profile of lncRNAs, including PACER, CILinc01, and CILinc02. Differential
      expression of CILinc01 and CIinc02 in hip and knee OA cartilage, and their role
      in modulating cytokine production during the chondrocyte inflammatory response,
      suggest that they may play an important role in mediating inflammation-driven
      cartilage degeneration in OA.

PMID- 27023364
TI  - A Case-Control Study Indicates that no Association Exists Between Polymorphisms
      of IL-33 and IL-1RL1 and Preeclampsia.
AB  - BACKGROUND/AIMS: Preeclampsia (PE) is a systemic inflammatory response syndrome
      involving varieties of cytokines, and previous studies have shown that IL-33 and
      its receptor IL-1RL1 play pivotal roles in the development of it. As a
      polygenetic hereditary disease, it is necessary to study the gene analysis for
      PE. Therefore, the present study was to determine whether IL-33 rs3939286 and IL
      1RL1 rs13015714 associated with susceptibility to PE in Chinese Han women.
      METHODS: 1,031 PE patients and 1,298 controls were enrolled and the genotyping
      for rs3939286 in IL-33 and rs13015714 in IL-1RL1 was performed by TaqMan allelic
      discrimination real-time PCR. Hardy-Weinberg equilibrium (HWE) was examined to
      ensure the group representativeness and Pearson's chi-square test was used to
      compare the differences in genetic distributions between the two groups. RESULTS:
      No significant differences in genotypic and allelic frequencies of the two
      polymorphisms loci were observed between cases and controls. There were also no
      significant differences in genetic distributions between mild/severe and
      early/late-onset PE and control groups. CONCLUSION: Although our data suggested
      that the polymorphisms of IL-33 rs3939286 and IL-1RL1 rs13015714 might not be
      critical risk factors for PE in Chinese Han women, the results need to be
      validated in different nations.

PMID- 27023365
TI  - Image Analysis of Optical Coherence Tomography Angiography.
AB  - Optical coherence tomography (OCT) angiography (OCT-A) is a transformative
      approach in imaging ocular vessels based on flow rather than simple reflectance
      intensity. It is therefore a functional extension of OCT that can be used to
      visualize microvasculature by detecting motion contrast from flowing blood. As
      OCT-A is a depth-resolved examination, it needs careful axial segmentation in
      order to preserve important data on perfused structures and to avoid the risk of
      generating superimposed images, which are typical of dye angiographies. An
      automated segmentation algorithm for both retinal and choroidal layers is
      provided by the majority of different OCT-A devices. In the case of accentuated
      macular retinal/choroidal disruptions causing potential segmentation errors,
      specific manual correction allows one to modify the shape and the localization of
      each layer. In the case of manual segmentation, the thickness of every C-scan may
      be modified in order to provide a constant thickness of tissue slices at
      different retinal or choroidal levels. OCT projection artifacts also occur from
      superficial retinal vessels, which can be seen in deeper retinal layers, or
      retinal and choroidal vessels, which can even be seen in the scleral tissue.
      These projection artifacts are almost always present and are visible in any layer
      that is located below the perfused vasculature. 

PMID- 27023366
TI  - Relating Translational Neuroimaging and Amperometric Endpoints: Utility for
      Neuropsychiatric Drug Discovery.
AB  - Measures of neuronal activation are a natural and parsimonious translational
      biomarker to consider in the context of neuropsychiatric drug discovery studies.
      In this regard, functional neuroimaging using the BOLD fMRI technique is becoming
      more frequently employed to not only probe aberrant brain regions and circuits in
      disease, but also to assess the effects of novel pharmacological agents on these
      processes. In the ideal situation, these types of studies would first be
      conducted pre-clinically in rodents to confirm a measurable functional response
      on relevant brain circuits before seeking to replicate the findings in an
      analogous fMRI paradigm in humans. However, the need for animal immobilization
      during the scanning procedure precludes all but the simplest behavioural task
      based paradigms in rodent BOLD fMRI. This chapter considers how in vivo oxygen
      amperometry may represent a viable and valid proxy for BOLD fMRI in freely moving
      rodents engaged in behavioural tasks. The amperometric technique and several
      examples of emerging evidence are described to show how the technique can deliver
      results that translate to pharmacological, event-related and functional
      connectivity variants of fMRI. In vivo oxygen amperometry holds great promise as
      a technique that may help to bridge the gap between basic drug discovery research
      in rodents and applied efficacy testing in humans. 

PMID- 27023367
TI  - RNAi Trigger Delivery into Anopheles gambiae Pupae.
AB  - RNA interference (RNAi), a naturally occurring phenomenon in eukaryotic
      organisms, is an extremely valuable tool that can be utilized in the laboratory
      for functional genomic studies. The ability to knockdown individual genes
      selectively via this reverse genetic technique has allowed many researchers to
      rapidly uncover the biological roles of numerous genes within many organisms, by
      evaluation of loss-of-function phenotypes. In the major human malaria vector
      Anopheles gambiae, the predominant method used to reduce the function of targeted
      genes involves injection of double-stranded (dsRNA) into the hemocoel of the
      adult mosquito. While this method has been successful, gene knockdown in adults
      excludes the functional assessment of genes that are expressed and potentially
      play roles during pre-adult stages, as well as genes that are expressed in
      limited numbers of cells in adult mosquitoes. We describe a method for the
      injection of Serine Protease Inhibitor 2 (SRPN2) dsRNA during the early pupal
      stage and validate SRPN2 protein knockdown by observing decreased target protein
      levels and the formation of melanotic pseudo-tumors in SRPN2 knockdown adult
      mosquitoes. This evident phenotype has been described previously for adult stage
      knockdown of SRPN2 function, and we have recapitulated this adult phenotype by
      SRPN2 knockdown initiated during pupal development. When used in conjunction with
      a dye-labeled dsRNA solution, this technique enables easy visualization by simple
      light microscopy of injection quality and distribution of dsRNA in the hemocoel. 

PMID- 27023368
TI  - The European Portuguese WHOQOL-OLD module and the new facet Family/Family life:
      reliability and validity studies.
AB  - PURPOSE: The aim of this study was to examine the psychometric properties of the
      European Portuguese version of the World Health Organization Quality of Life
      Older Adults Module (WHOQOL-OLD). The European Portuguese WHOQOL-OLD includes a
      new identified facet, Family/Family life. METHODS: A convenience sample of older
      adults was recruited (N = 921). The assessment protocol included demographics,
      self-perceived health, depressive symptoms (GDS-30), cognitive function (ACE-R),
      daily life activities (IAFAI), health status (SF-12) and QoL (WHOQOL-Bref,
      EUROHIS-QOL-8 and WHOQOL-OLD). RESULTS: The internal consistency was excellent
      for the total 24-item WHOQOL-OLD original version and also for the final 28-item
      European Portuguese WHOQOL-OLD version. The test-retest reliability for total
      scores was good. The construct validity of the European Portuguese WHOQOL-OLD was
      supported in the correlation matrix analysis. The results indicated good
      convergent/divergent validity. The WHOQOL-OLD scores differentiated groups of
      older adults who were healthy/unhealthy and without/mild/severe depressive
      symptoms. The new facet, Family/Family life, presented evidence of good
      reliability and validity parameters. CONCLUSION: Comparatively to international
      studies, the European Portuguese WHOQOL-OLD version showed similar and/or better
      psychometric properties. The new facet, Family/Family life, introduces cross
      cultural specificity to the study of QoL of older adults and generally improves
      the psychometric robustness of the WHOQOL-OLD.

PMID- 27023369
TI  - Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic
      Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling
      Pathways.
AB  - Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD)
      patients is common. Neuromuscular Electrical Stimulation (NMES) is a powerful
      exercise training that may relieve muscle dysfunction in COPD. This study
      investigated whether electrical stimulation may have atypical adaptations via
      activation of miRNA related pathways in counteracting COPD muscle dysfunction.
      Forty-eight male Sprague-Dawley rats were randomly assigned to 3 groups. With the
      exception of the rats in the control group, the experimental rats were exposed to
      chronic intermittent hypoxia-hypercapnia (CIHH) (9~11%O2,5.5~6.5%CO2) for 2 or 4
      weeks. Electrical stimulation was performed immediately after each CIHH session.
      Following assessment of the running capacity, biopsy samples were obtained from
      the gastrocnemius of the rats. The miR-1, miR-133a and miR-133b levels were
      measured, as well as their related proteins: phosphorylation of Akt (p-AKT), PGC
      1alpha (PGC-1alpha), histone deacetylase 4 (HDAC4) and serum response factor
      (SRF). Myosin heavy chainIIa (MHCIIa) and myosin heavy chainIIb (MHCIIb) were
      also measured to assess fiber type changes. After 2 weeks, compared with the
      controls, only miR-1 and miR-133a were significantly increased (p<0.05) in the
      exposure group. After 4 weeks, the exposure group exhibited a decreased running
      distance (p = 0.054) and MHCIIa-to-MHCIIb shift (p<0.05). PGC-1alpha (p = 0.051),
      nuclear HDAC4 (p = 0.058), HDAC4, p-AKT, PGC-1alpha and SRF was also
      significantly decreased (p<0.05). In contrast, miR-1 and miR-133a were
      significantly increased (p<0.05). Four weeks of electrical stimulation can partly
      reversed those changes, and miR-133b exhibited a transient increase after 2 weeks
      electrical stimulation. Our study indicate miRNAs may have roles in the response
      of CIHH-impaired muscle to changes during electrical stimulation.

PMID- 27023370
TI  - Homogeneous Protein Analysis by Magnetic Core-Shell Nanorod Probes.
AB  - Studying protein interactions is of vital importance both to fundamental biology
      research and to medical applications. Here, we report on the experimental proof
      of a universally applicable label-free homogeneous platform for rapid protein
      analysis. It is based on optically detecting changes in the rotational dynamics
      of magnetically agitated core-shell nanorods upon their specific interaction with
      proteins. By adjusting the excitation frequency, we are able to optimize the
      measurement signal for each analyte protein size. In addition, due to the locking
      of the optical signal to the magnetic excitation frequency, background signals
      are suppressed, thus allowing exclusive studies of processes at the nanoprobe
      surface only. We study target proteins (soluble domain of the human epidermal
      growth factor receptor 2 - sHER2) specifically binding to antibodies
      (trastuzumab) immobilized on the surface of our nanoprobes and demonstrate direct
      deduction of their respective sizes. Additionally, we examine the dependence of
      our measurement signal on the concentration of the analyte protein, and deduce a
      minimally detectable sHER2 concentration of 440 pM. For our homogeneous
      measurement platform, good dispersion stability of the applied nanoprobes under
      physiological conditions is of vital importance. To that end, we support our
      measurement data by theoretical modeling of the total particle-particle
      interaction energies. The successful implementation of our platform offers scope
      for applications in biomarker-based diagnostics as well as for answering basic
      biology questions. 

PMID- 27023371
TI  - 'Public enemy no. 1': Tobacco industry funding for the AIDS response.
AB  - This article analyzes the history of tobacco industry funding for the AIDS
      response - a largely ignored aspect of private donor involvement. Primary
      documents from the Legacy Tobacco Documents Library and AIDS organizations are
      analyzed, alongside existing literature on the tobacco control and AIDS
      responses. Research on the tactics of transnational tobacco companies has
      documented how they have used various charitable causes to subvert tobacco
      control efforts and influence public health policy. This raises questions, which
      this paper seeks to answer, about if donations by tobacco companies to AIDS
      organizations have been used for similar means, and if so how AIDS organizations
      have responded to tobacco industry overtures. Two examples illustrate how tobacco
      companies initially tried to use the AIDS response to counter tobacco control
      measures: (1) During the 1990s, Philip Morris, one of the largest corporate
      donors of the AIDS response in the USA, used its connections with AIDS
      organizations to create competition for health resources, improve its reputation,
      and market tobacco products to the LGBT community; (2) In both Latin America and
      sub-Saharan Africa, Philip Morris and British American Tobacco championed the
      AIDS response in order to delegitimize efforts to develop the World Health
      Organization's Framework Convention on Tobacco Control. However, from the late
      1990s onwards, AIDS organizations began to refuse tobacco funding and
      partnerships - though these policies have been not comprehensive, as many tobacco
      companies still fund programs in sub-Saharan Africa. The article concludes that
      tobacco companies aimed to exploit competition between health issues, and use the
      high-profile AIDS response to improve their reputation and market access.
      However, AIDS organizations, adhering to broader health goals and drawing on
      extensive resources and networks, were able to shut the tobacco industry out of
      much of the response, though pockets of influence still exist. This demonstrates
      the importance of co-operation and policy convergence across health sectors and
      suggests that tobacco control advocates, and other charitable sectors that
      receive funding from the tobacco industry, may be able to draw lessons from the
      experiences of AIDS organizations. 

PMID- 27023372
TI  - Nonamplification Sandwich Assay Platform for Sensitive Nucleic Acid Detection
      Based on AuNPs Enumeration with the Dark-Field Microscope.
AB  - A simple and efficient assay platform with high sensitivity, convenient
      implementation, and moderate cost in reagents and instrumentation is most
      appropriate for routine applications. On the basis of the gold nanoparticle
      (AuNP) enumeration signal readout mode established in our laboratory, we have
      developed a nonamplification sandwich assay for nucleic acid detection with the 3
      fM limit of detection for a sequence related to Alzheimer's disease. This AuNP
      counting based method takes advantages of the distinctive and strong localized
      surface plasmon resonance light scattering with the dark-field microscope and
      magnetic separation. It is shown that the presence of 20 nM random DNA sequence
      or calf thymus DNA with a mass up to 10(6)-fold of the targets do not
      significantly interfere with the assay signal. The spike recoveries of Hela cell
      lysate sample at 109.3% for 20 pM target and 110.5% for 100 pM target indicate
      the potential of this proposed method in practical sample applications. This
      nonamplification sandwich assay platform in principle is applicable to other
      assays such as the immunoassay and thus would be expected to find a breadth of
      applications that can make the best use of the simplicity and sensitivity. 

PMID- 27023373
TI  - Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered
      by Genome Mining.
AB  - Photoreactive siderophores have a major impact on the growth of planktonic
      organisms. To date, these molecules have mainly been reported from marine
      bacteria, although evidence is now accumulating that some terrestrial bacteria
      also harbor the biosynthetic potential for their production. In this paper, we
      describe the genomics-driven discovery and characterization of variochelins,
      lipopeptide siderophores from the bacterium Variovorax boronicumulans, which
      thrives in soil and freshwater habitats. Variochelins are different from most
      other lipopeptide siderophores in that their biosynthesis involves a polyketide
      synthase. We demonstrate that the ferric iron complex of variochelin A possesses
      photoreactive properties and present the MS-derived structures of two degradation
      products that emerge upon light exposure. 

PMID- 27023374
TI  - Protocol for Measuring the Thermal Properties of a Supercooled Synthetic Sand
      water-gas-methane Hydrate Sample.
AB  - Methane hydrates (MHs) are present in large amounts in the ocean floor and
      permafrost regions. Methane and hydrogen hydrates are being studied as future
      energy resources and energy storage media. To develop a method for gas production
      from natural MH-bearing sediments and hydrate-based technologies, it is
      imperative to understand the thermal properties of gas hydrates. The thermal
      properties' measurements of samples comprising sand, water, methane, and MH are
      difficult because the melting heat of MH may affect the measurements. To solve
      this problem, we performed thermal properties' measurements at supercooled
      conditions during MH formation. The measurement protocol, calculation method of
      the saturation change, and tips for thermal constants' analysis of the sample
      using transient plane source techniques are described here. The effect of the
      formation heat of MH on measurement is very small because the gas hydrate
      formation rate is very slow. This measurement method can be applied to the
      thermal properties of the gas hydrate-water-guest gas system, which contains
      hydrogen, CO2, and ozone hydrates, because the characteristic low formation rate
      of gas hydrate is not unique to MH. The key point of this method is the low rate
      of phase transition of the target material. Hence, this method may be applied to
      other materials having low phase-transition rates. 

PMID- 27023375
TI  - Platelet Function in Thrombosis and Hemostasis.

PMID- 27023376
TI  - Full-Dimensional Quantum Calculations of Vibrational Levels of NH4(+) and
      Isotopomers on An Accurate Ab Initio Potential Energy Surface.
AB  - Vibrational energy levels of the ammonium cation (NH4(+)) and its deuterated
      isotopomers are calculated using a numerically exact kinetic energy operator on a
      recently developed nine-dimensional permutation invariant semiglobal potential
      energy surface fitted to a large number of high-level ab initio points. Like CH4,
      the vibrational levels of NH4(+) and ND4(+) exhibit a polyad structure,
      characterized by a collective quantum number P = 2(v1 + v3) + v2 + v4. The low
      lying vibrational levels of all isotopomers are assigned and the agreement with
      available experimental data is better than 1 cm(-1). 

PMID- 27023378
TI  - Keratinocytes express functional CARD18, a negative regulator of inflammasome
      activation, and its altered expression in psoriasis may contribute to disease
      pathogenesis.
AB  - Caspase recruitment domain family member 18 (CARD18, Iceberg) is known as a
      negative regulatory molecule that inhibits inflammatory events by terminating
      inflammasome activation due to a direct interaction with pro-caspase-1. During
      the investigation of molecular mechanisms in keratinocytes that contribute to the
      pathogenesis of psoriasis, we found that CARD18 expression differs in healthy and
      psoriatic skin; moreover, CARD18 demonstrated altered response under inflammatory
      conditions in healthy and psoriatic skin. In healthy skin, low basal CARD18
      expression was detected, which showed significant elevation in response to
      inflammatory stimuli (lymphokine treatment or mechanical injury). In contrast,
      higher basal expression was observed in psoriatic non-involved skin, but no
      further induction could be detected. We demonstrated that keratinocytes express
      CARD18 both at mRNA and protein levels and the expression increased in parallel
      with differentiation. The investigation of cellular inflammatory processes
      revealed that psoriasis-associated danger signals triggered the expression of
      inflammasome components (AIM2, Caspase-1) and CARD18 as well as IL-1beta
      production of keratinocytes. Furthermore, gene-specific silencing of CARD18 in
      cells treated with cytosolic DNA (poly(dA:dT)) resulted in increased IL-1beta
      secretion, suggesting a negative regulatory role for CARD18 in keratinocyte
      inflammatory signaling. The differential regulation of CARD18 in healthy and
      psoriatic uninvolved epidermis may contribute to the susceptibility of psoriasis.
      Furthermore, our in vitro results indicate that CARD18 may contribute to the fine
      tuning of keratinocyte innate immune processes.

PMID- 27023377
TI  - A Versatile Murine Model of Subcortical White Matter Stroke for the Study of
      Axonal Degeneration and White Matter Neurobiology.
AB  - Stroke affecting white matter accounts for up to 25% of clinical stroke
      presentations, occurs silently at rates that may be 5-10 fold greater, and
      contributes significantly to the development of vascular dementia. Few models of
      focal white matter stroke exist and this lack of appropriate models has hampered
      understanding of the neurobiologic mechanisms involved in injury response and
      repair after this type of stroke. The main limitation of other subcortical stroke
      models is that they do not focally restrict the infarct to the white matter or
      have primarily been validated in non-murine species. This limits the ability to
      apply the wide variety of murine research tools to study the neurobiology of
      white matter stroke. Here we present a methodology for the reliable production of
      a focal stroke in murine white matter using a local injection of an irreversible
      eNOS inhibitor. We also present several variations on the general protocol
      including two unique stereotactic variations, retrograde neuronal tracing, as
      well as fresh tissue labeling and dissection that greatly expand the potential
      applications of this technique. These variations allow for multiple approaches to
      analyze the neurobiologic effects of this common and understudied form of stroke.

PMID- 27023379
TI  - [Satisfaction of patients with tracheostomal epithesis].
AB  - BACKGROUND: The utilization of craniofacial prosthesis has proven to be very
      successful for craniofacial defects. However, there is a lack of knowledge about
      the value of an epithesis for voice rehabilitation in patients with tracheostomy.
      The aim of this study was to describe application of the tracheostomy epithesis
      and to present a systematic analysis of the functional results of this prosthetic
      technique. MATERIALS AND METHODS: This retrospective analysis included 48
      patients on follow-up being treated in three different centers after laryngectomy
      and/or tracheostomy between 2008 and 2014. Subjects were given a questionnaire
      with items such as speech quality, quality of life, free hand speech ability,
      respiratory quality and sufficient tracheostomal sealing comparing values before
      and after application of an individually custom-made tracheostomy epithesis.
      Twenty-eight answered the questionnaire and could be reported. RESULTS: Twenty
      eight of 48 patients were consistently being included in follow-up. The
      statistical analysis revealed a significant improvement of tracheostoma occlusion
      (p < 0.05) and improvement in free hand speech ability (p < 0.05). A leakage of
      air during voice production could be prevented in 59.3% after application of an
      epithesis. Quality of life correlated directly with successful utilization of an
      epithesis. CONCLUSION: In the literature, different industrialized products are
      described to realize occlusion of the tracheostoma for sufficient speech
      production without using the hands. In numerous cases commercial solutions fail
      and the patients need individual modifications. Our study first describes the
      evaluation of custom-made tracheostomal epithesis. From our observed results we
      advocate the individual tracheostomal epithesis as a durable solution for voice
      rehabilitation.

PMID- 27023380
TI  - Anammox for nitrogen removal from anaerobically pre-treated municipal wastewater:
      Effect of COD/N ratios on process performance and bacterial community structure.
AB  - Long-term effects of COD/N ratios on the nitrogen removal performance and
      bacterial community of an anammox reactor were evaluated by adding a synthetic
      medium (with glucose) and real anaerobic effluent to a SBR. At a COD/N ratio of
      2.8 (COD, 390mg.L(-1)) ammonium removal efficiency was 66%, while nitrite removal
      remained high (99%). However, at a COD/N ratio of 5.0 (COD, 300mg.L(-1)),
      ammonium and nitrite removal efficiencies were high (84% and 99%, respectively).
      High COD, nitrite, and ammonium removal efficiencies (80%, 90% and 95%,
      respectively) were obtained on adding anaerobically pre-treated municipal
      wastewater (with nitrite) to the reactor. DGGE revealed that the addition of
      anaerobic effluent changed the bacterial community structure and selected for DNA
      sequences related to Brocadia sinica and Chloroflexi. Adding glucose and
      anaerobic effluent increased denitrifiers concentration threefold. Thus, the
      possibility of using the anammox process to remove nitrogen from anaerobically
      pre-treated municipal wastewater was demonstrated. 

PMID- 27023381
TI  - Conversion of polyhydroxyalkanoates to methyl crotonate using whole cells.
AB  - Isolated polyhydroxyalkanoates (PHA) can be used to produce biobased bulk
      chemicals. However, isolation is complex and costly. To circumvent this, whole
      cells containing PHA may be used. Here, PHA containing 3-hydroxybutyrate and
      small amounts of 3-hydroxyvalerate was produced from wastewater and used in the
      conversion of the 3-hydroxybutyrate monomer to methyl crotonate. Due to the
      increased complexity of whole cell reaction mixtures compared to pure PHA, the
      effect of 3-hydroxyvalerate content, magnesium salts and water content was
      studied in order to evaluate the need for downstream processing. A water content
      up to 20% and the presence of 3-hydroxyvalerate have no influence on the
      conversion of the 3-hydroxybutyrate to methyl crotonate. The presence of Mg(2+)
      ions resulted either in an increased yield or in byproduct formation depending on
      the counter ion. Overall, it is possible to bypass a major part of the downstream
      processing of PHA for the production of biobased chemicals. 

PMID- 27023382
TI  - Suspended sludge and biofilm shaped different anammox communities in two pilot
      scale one-stage anammox reactors.
AB  - The abundance and diversity of anammox bacteria was investigated in two pilot
      scale integrated fixed-film activated sludge (IFAS) reactors treating high
      ammonium wastewater. Reactor A was inoculated with nitrifying sludge, while
      Reactor B was inoculated with suspended anammox sludge with the dominant anammox
      bacteria of Candidatus 'Kuenenia'. After 180days' operation, the predominate
      anammox bacteria was Candidatus 'Brocadia' (65%) in the biofilm, while Candidatus
      'Kuenenia' (86%) outcompeted with other anammox bacteria in suspended sludge in
      Reactor A. Candidatus 'Kuenenia' were dominated in suspended sludge through the
      entire experiment in Reactor B. In contrast, the predominated species shifted
      from Candidatus 'Kuenenia' (89%) into Candidatus 'Brocadia' (66%) in the biofilm
      of Reactor B. This study indicated that Candidatus 'Brocadia' preferred to grow
      in the biofilm, while Candidatus 'Kuenenia' would dominant over other anammox
      bacteria in the suspended sludge. Further studies are required to identify the
      internal factors affecting the distribution of anammox bacteria. 

PMID- 27023383
TI  - Second-generation ethanol production from elephant grass at high total solids.
AB  - The enzymatic hydrolysis of Pennisetum purpureum (elephant grass) was evaluated
      at high total solid levels (from 4% to 20% (w/v)) in a concomitant ball milling
      treatment in a rotating hydrolysis reactor (RHR). The greatest glucose yield was
      20.17% when 4% (w/v) untreated biomass was employed. When sugars obtained from
      enzymatic hydrolysis were submitted to fermentation with Saccharomyces
      cerevisiae, the greatest ethanol yield was 22.61% when 4% (w/v) untreated biomass
      was employed; however, the highest glucose concentration (12.47g/L) was obtaining
      using 20% (w/v) solids and highest ethanol concentration (6.1g/L) was obtained
      using 16% (w/v) solids. When elephant grass was hydrolyzed in the rotating
      hydrolysis reactor, ethanol production was about double that was produced when
      the biomass was hydrolyzed in a static reactor (SR). These data indicate that it
      is possible to produce ethanol from elephant grass when milling treatment and
      enzymatic hydrolysis are performed at the same time. 

PMID- 27023384
TI  - Improvement of l-lactic acid productivity from sweet sorghum juice by repeated
      batch fermentation coupled with membrane separation.
AB  - In order to efficiently produce l-lactic acid from non-food feedstocks, sweet
      sorghum juice (SSJ), which is rich of fermentable sugars, was directly used for l
      lactic acid fermentation by Lactobacillus rhamnosus LA-04-1. A membrane
      integrated repeated batch fermentation (MIRB) was developed for productivity
      improvement. High-cell-density fermentation was achieved with a final cell
      density (OD620) of 42.3, and the CCR effect was overcomed. When SSJ (6.77gL(-1)
      glucose, 4.51gL(-1) fructose and 50.46gL(-1) sucrose) was used as carbon source
      in MIRB process, l-lactic acid productivity was increased significantly from
      1.45gL(-1)h(-1) (batch 1) to 17.55gL(-1)h(-1) (batch 6). This process introduces
      an effective way to produce l-lactic acid from SSJ. 

PMID- 27023385
TI  - Improving phosphorus removal in aerobic granular sludge processes through
      selective microbial management.
AB  - This study aimed to improve phosphorus removal in aerobic granular sludge
      sequential batch reactors (AGS-SBR) by a differential selection of the granules
      containing the highest proportion of phosphate accumulating organisms (PAOs). The
      abundance of PAOs in granules with different density was analyzed by PCR-DGGE,
      pyrosequencing and qPCR. Dense granules contained a higher proportion of
      Candidatus Accumulibacter (PAO) with a 16S rRNA gene frequency up to 45%.
      Starting with an AGS-SBR with low height/diameter ratio performing unstable P
      removal, two strategies of biomass removal were assessed. First, a high selective
      pressure (short settling time) was applied and second, an increase of the
      settling time was combined with a homogeneous purge of the sludge bed. The first
      strategy resulted in a reduction of P removal efficiency while the second
      improved and stabilized P removal over 90%. This study offers a new approach of
      biomass management in AGS-SBR. 

PMID- 27023386
TI  - Succinic acid production from duckweed (Landoltia punctata) hydrolysate by batch
      fermentation of Actinobacillus succinogenes GXAS137.
AB  - Duckweed is potentially an ideal succinic acid (SA) feedstock due to its high
      proportion of starch and low lignin content. Pretreatment methods, substrate
      content and nitrogen source were investigated to enhance the bioconversion of
      duckweed to SA and to reduce the costs of production. Results showed that acid
      hydrolysis was an effective pretreatment method because of its high SA yield. The
      optimum substrate concentration was 140g/L. The optimum substrate concentration
      was 140g/L. Corn steep liquor powder could be considered a feasible and
      inexpensive alternative to yeast extract as a nitrogen source. Approximately
      57.85g/L of SA was produced when batch fermentation was conducted in a 1.3L
      stirred bioreactor. Therefore, inexpensive duckweed can be a promising feedstock
      for the economical and efficient production of SA through fermentation by
      Actinobacillus succinogenes GXAS137. 

PMID- 27023387
TI  - Efficient harvesting of wet blue-green microalgal biomass by two-aminoclay [AC]
      mixture systems.
AB  - Blue-green microalgal blooms have been caused concerns about environmental
      problems and human-health dangers. For removal of such cyanobacteria, many
      mechanical and chemical treatments have been trialled. Among various
      technologies, the flocculation-based harvesting (precipitation) method can be an
      alternative if the problem of the low yield of recovered biomass at low
      concentrations of cyanobacteria is solved. In the present study, it was utilized
      mixtures of magnesium aminoclay [MgAC] and cerium aminoclay [CeAC] with different
      particle sizes to harvest cyanobacteria feedstocks with ~100% efficiency within
      1h by ten-fold lower loading of ACs compared with single treatments of [MgAC] or
      [CeAC]. This success was owed to the compact networks of the different-sized-ACs
      mixture for efficient bridging between microalgal cells. In order to determine
      the usage potential of biomass harvested with AC, the mass was heat treated under
      the reduction condition. This system is expected to be profitably utilizable in
      adsorbents and catalysts. 

PMID- 27023388
TI  - Bioaugmentation of Hydrogenispora ethanolica LX-B affects hydrogen production
      through altering indigenous bacterial community structure.
AB  - Bioaugmentation can facilitate hydrogen production from complex organic
      substrates, but it still is unknown how indigenous microbial communities respond
      to the added bacteria. Here, using a Hydrogenispora ethanolica LX-B (named as LX
      B) bioaugmentation experiments, the distribution of metabolites and the responses
      of indigenous bacterial communities were investigated via batch cultivation (BC)
      and repeated batch cultivation (RBC). In BC the LX-B/sludge ratio of 0.12
      achieved substantial high hydrogen yield, which was over twice that of control.
      In RBC one-time bioaugmentation and repeated batch bioaugmentation of LX-B
      resulted in the hydrogen yield that was average 1.2-fold and 0.8-fold higher than
      that in control, respectively. This improved hydrogen production performance
      mainly benefited from a shift in composition of the indigenous bacterial
      community caused by LX-B bioaugmentation. The findings represented an important
      step in understanding the relationship between bioaugmentation, a shift in
      bacterial communities, and altered bioreactor performance. 

PMID- 27023389
TI  - Quantitative Fundus Autofluorescence for the Evaluation of Retinal Diseases.
AB  - The retinal pigment epithelium (RPE) is juxtaposed to the overlying sensory
      retina, and supports the function of the visual system. Among the tasks performed
      by the RPE are phagocytosis and processing of outer photoreceptor segments
      through lysosome-derived organelles. These degradation products, stored and
      referred to as lipofuscin granules, are composed partially of bisretinoids, which
      have broad fluorescence absorption and emission spectra that can be detected
      clinically as fundus autofluorescence with confocal scanning laser ophthalmoscopy
      (cSLO). Lipofuscin accumulation is associated with increasing age, but is also
      found in various patterns in both acquired and inherited degenerative diseases of
      the retina. Thus, studying its pattern of accumulation and correlating such
      patterns with changes in the overlying sensory retina are essential to
      understanding the pathophysiology and progression of retinal disease. Here, we
      describe a technique employed by our lab and others that uses cSLO in order to
      quantify the level of RPE lipofuscin in both healthy and diseased eyes. 

PMID- 27023390
TI  - Prognostic value of funisitis and/or chorionic vasculitis compared to histologic
      chorioamnionitis in full-term infants.
AB  - AIM: To compare pathological findings in the placenta and cord with the prognosis
      of full-term infants in cases of neonatal infection and microbial analyses.
      METHODS: The pathological findings in the placenta and cord and microbial
      analyses of amniotic fluid and neonatal samples based on culture or polymerase
      chain reaction (PCR) were observed in 1208 full-term mother-infant pairs at our
      center. We also collected neonatal clinical infection data, such as the
      occurrence of septicemia and other infectious diseases. RESULTS: Neonatal
      infection and positive identification of microorganisms were more common in the
      funisitis and/or chorionic vasculitis group than in the histologic
      chorioamnionitis group. CONCLUSION: Funisitis and/or chorionic vasculitis is a
      valuable pathological marker for assessing the comparison between intrauterine
      infection and neonatal inflammatory conditions in infants delivered at full-term.

PMID- 27023391
TI  - Examining the Relationship between Pre-Malignant Breast Lesions, Carcinogenesis
      and Tumor Evolution in the Mammary Epithelium Using an Agent-Based Model.
AB  - INTRODUCTION: Breast cancer, the product of numerous rare mutational events that
      occur over an extended time period, presents numerous challenges to investigators
      interested in studying the transformation from normal breast epithelium to
      malignancy using traditional laboratory methods, particularly with respect to
      characterizing transitional and pre-malignant states. Dynamic computational
      modeling can provide insight into these pathophysiological dynamics, and as such
      we use a previously validated agent-based computational model of the mammary
      epithelium (the DEABM) to investigate the probabilistic mechanisms by which
      normal populations of ductal cells could transform into states replicating
      features of both pre-malignant breast lesions and a diverse set of breast cancer
      subtypes. METHODS: The DEABM consists of simulated cellular populations governed
      by algorithms based on accepted and previously published cellular mechanisms.
      Cells respond to hormones, undergo mitosis, apoptosis and cellular
      differentiation. Heritable mutations to 12 genes prominently implicated in breast
      cancer are acquired via a probabilistic mechanism. 3000 simulations of the 40
      year period of menstrual cycling were run in wild-type (WT) and BRCA1-mutated
      groups. Simulations were analyzed by development of hyperplastic states,
      incidence of malignancy, hormone receptor and HER-2 status, frequency of mutation
      to particular genes, and whether mutations were early events in carcinogenesis.
      RESULTS: Cancer incidence in WT (2.6%) and BRCA1-mutated (45.9%) populations
      closely matched published epidemiologic rates. Hormone receptor expression
      profiles in both WT and BRCA groups also closely matched epidemiologic data.
      Hyperplastic populations carried more mutations than normal populations and
      mutations were similar to early mutations found in ER+ tumors (telomerase, E
      cadherin, TGFB, RUNX3, p < .01). ER- tumors carried significantly more mutations
      and carried more early mutations in BRCA1, c-MYC and genes associated with
      epithelial-mesenchymal transition. CONCLUSIONS: The DEABM generates diverse
      tumors that express tumor markers consistent with epidemiologic data. The DEABM
      also generates non-invasive, hyperplastic populations, analogous to atypia or
      ductal carcinoma in situ (DCIS), via mutations to genes known to be present in
      hyperplastic lesions and as early mutations in breast cancers. The results
      demonstrate that agent-based models are well-suited to studying tumor evolution
      through stages of carcinogenesis and have the potential to be used to develop
      prevention and treatment strategies.

PMID- 27023392
TI  - Growing skull fractures: guidelines for early diagnosis and surgical management.
AB  - BACKGROUND: Growing skull fracture (GSF) is a rare complication of pediatric head
      trauma and causes delayed onset neurological deficits and cranial defect. GSF
      usually develops following linear fracture with underlying dural tear resulting
      in herniation of the brain. Early diagnosis and treatment are essential to avoid
      complications. However, there are no clear-cut guidelines for the early diagnosis
      of GSF. The present study was conducted to identify the criteria for the early
      diagnosis of GSF. MATERIAL AND METHODS: From 2010 to 2015, all pediatric patients
      of head trauma with linear fracture were evaluated. Patients of age <5 years with
      cephalhematoma, bone diastasis of 4 mm or more with underlying brain contusion
      were subjected to contrast brain MRI to find out the dural tear and herniation of
      the brain matter. Patients with contrast MRI showing dural tear and herniation of
      the brain matter were considered high risk for the development of GSF and treated
      surgically within 1 month of trauma. Patients with contrast brain MRI not showing
      dural tear and herniation of the brain matter were regularly followed for any
      signs of GSF. RESULTS: A total of 20 patients were evaluated, out of which 16
      showed dural defects with herniation of the brain matter and were subjected to
      duraplasty. Four patients in which MRI did not show dural tear and herniation of
      the brain matter were regularly followed-up and have not shown any sign of GSF
      later on follow-up. CONCLUSION: Early diagnosis of GSF can be made based on the
      four criteria, i.e., (1) age <5 year with cephalhematoma, (2) bone diastasis 4 mm
      or more (3) underlying brain contusion (4) contrast MRI showing dural tear and
      herniation of the brain matter. Dural tear with herniation of the brain matter is
      the main etiopathogenic factor for the development of GSF. Early diagnosis and
      treatment of GSF can yield a good outcome.

PMID- 27023393
TI  - The 1966 Ciba Symposium on Transplantation Ethics: 50 Years Later.
AB  - In March 1966, the Ciba Foundation sponsored the first international,
      interdisciplinary symposium focused on ethical and legal issues in
      transplantation. The attendees included not only physicians and surgeons but also
      judges and legal scholars, a minister, and a science journalist. In this article,
      we will consider some of the topics in organ transplantation that were discussed
      by the attendees, what we have learned in the intervening half century, and the
      relevance of their discussions today. Specifically, we examine the definition of
      death and its implications for organ procurement, whether it is ethical and legal
      to "maim" a living individual for the benefit of another, how to ensure that the
      consent of the living donor is voluntary and informed, the case of identical
      twins, the question of whether ethically minors can serve as living donors, the
      health risks of living donation, the ethics and legality of an organ market, and
      the economic barriers to living donation. We show that many of the concerns
      discussed at the Ciba symposium remain highly relevant, and their discussions
      have helped to shape the ethical boundaries of organ transplantation today. 

PMID- 27023395
TI  - Zika Virus and Solid Organ Transplantation: Significant Pathogen or Harbinger of
      Things to Come?

PMID- 27023394
TI  - Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver
      Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter
      Study.
AB  - BACKGROUND: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is
      effective in preventing hepatitis B virus (HBV) recurrence after liver
      transplantation, but early conversion to subcutaneous administration is
      undocumented. METHODS: In a prospective study, patients transplanted for terminal
      liver disease due to HBV infection who were HBV DNA-negative at transplant were
      switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500
      or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough
      level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients
      concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint
      was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV
      reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS: Of 49 patients
      treated, 47 (95.9%) continued treatment until month 6. All patients achieved
      administration by a caregiver or self-injection by week 14. No treatment failures
      occurred. Mean anti-HBs declined progressively to month 6, plateauing at a
      protective titer of approximately 290 IU/L. All patients tested for HBV DNA
      remained negative (45/45). Only 1 adverse event (mild injection site hematoma)
      was assessed as treatment-related. CONCLUSIONS: Introduction of subcutaneous HBIg
      administration by week 3 posttransplantation, combined with HBV virostatic
      prophylaxis, is effective and convenient for preventing HBV recurrence.

PMID- 27023396
TI  - Alzheimer's disease and memory strength: Gradual decline of memory traces as a
      function of their strength.
AB  - OBJECTIVE: Episodic memory impairment is at the core of amnestic mild cognitive
      impairment (aMCI) and Alzheimer's disease (AD). The origin of memory deficits may
      result either from an encoding deficit or from an accelerated decline of the
      memory trace. The present study explores these two hypotheses. METHOD: We used
      the delayed-matching-to sample 48 items (DMS-48) memory test in a group of
      controls, aMCI patients, and AD patients (n= 16 in each group). The DMS-48 offers
      an incidental learning phase followed by three forced-choice recognition tests at
      three-minute, one-hour, and one-week delays. Moreover, the forced-choice test
      distinguishes three kinds of couple items: abstract (meaningless), paired (two
      similar exemplars), and unique (two different objects) items. RESULTS: As
      predicted by the accelerated forgetting hypothesis, patients showed a decrease in
      recognition performance over time. Controls also exhibited a similar decline in
      performance. As predicted by the encoding deficit hypothesis, abstract items were
      the most poorly recognized in AD, at both the three-minute and the one-week
      delays. In AD, recognition of the paired items also dropped after the one-hour
      delay, followed by unique items after a one-week delay. Patients with aMCI
      exhibited a performance that was similar to controls, except for abstract items,
      which dropped at the one-week delay. CONCLUSIONS: These results are discussed in
      light of a third hypothesis, the memory strength hypothesis, in order to better
      account for the progressive decline in memory performance as a function of the
      item type in AD.

PMID- 27023397
TI  - Analysis of the Physiological and Molecular Responses of Dunaliella salina to
      Macronutrient Deprivation.
AB  - The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its
      dry weight as beta-carotene in chloroplasts when subjected to adverse conditions,
      including nutrient deprivation. However, the mechanisms of carotenoid
      biosynthesis are poorly understood. Here, the physiological and molecular
      responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and
      different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were
      compared to gain insights into the underlying regulatory mechanisms of carotenoid
      biosynthesis. The results showed that both the growth and photosynthetic rates of
      cells were decreased during nutrient deprivation, accompanied by lipid globule
      accumulation and reduced chlorophyll levels. The SOD and CAT activities of the
      cells were altered during nutrient deprivation, but their responses were
      different. The total carotenoid contents of cells subjected to multiple nutrient
      deprivation were higher than those of cells subjected to single nutrient
      deprivation and non-stressed cells. The beta-carotene contents of cells subjected
      to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single
      nutrient deprivation. Cells subjected to sulfur deprivation accumulated more
      lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast,
      no cumulative effects of nutrient deprivation on the transcription of genes in
      the carotenogenic pathway were observed because MEP and carotenogenic pathway
      genes were up-regulated during single nutrient deprivation but were downregulated
      during multiple nutrient deprivation. Therefore, we proposed that the carotenoid
      biosynthesis pathway of D. salina is regulated at both the transcriptional and
      posttranscriptional levels and that a complex crosstalk occurs at the
      physiological and molecular levels in response to the deprivation of different
      nutrients. 

PMID- 27023398
TI  - Effects of folic acid supplementation during different pregnancy periods and
      relationship with the other primary prevention measures to neural tube defects.
AB  - OBJECTIVE: To find out the prevention effects of folic acid supplements during
      different pregnancy periods on neural tube defects (NTDs) and the relationship of
      folic acid supplements with the other NTDs' primary preventive measures. METHODS:
      A 1:1 case-control study was conducted. Four hundred and fifty-nine women who
      delivered or gestate infants/fetuses with NTDs in the last two years were
      randomly selected as cases and were matched with women who delivered babies
      without obvious birth defects as controls. RESULTS: For anencephaly, folic acid
      supplementation during the periconceptional period and preconceptional period has
      a 57-83% reduction in risk of NTDs(ORs ranged from 0.17 to 0.43). For spina
      bifida, folic acid supplementation during the periconceptional period has a 79%
      reduction in risk of NTDs (OR = 0.21). For encephalocele, folic acid
      supplementation during the periconceptional period has a 67% reduction in risk of
      NTDs (OR = 0.33). The prevention effects on NTDs were significant when these
      preventive measures combined with folic acid supplements during the
      periconceptional period, with OR 0.04, 0.07, 0.10 and 0.11. CONCLUSION: The
      specific effects of folic acid supplementation during different periods show the
      reduction in the risk of NTDs, anencephaly, spina bifida, encephalocele. During
      periconceptional period, folic acid supplements have preventive effects on all
      NTDs' subtypes.

PMID- 27023399
TI  - Acute seizures in cerebral venous sinus thrombosis: What predicts it?
AB  - BACKGROUND: Seizures are the presenting feature of cerebral venous sinus
      thrombosis (CVST) in 12-31.9% of patients. 44.3% of patients have seizures in the
      early stage of the disease. Acute seizures (AS), refers to seizures which take
      place before the diagnosis or during the first 2 weeks afterward. OBJECTIVE: To
      report the predictors of acute seizures in cerebral venous sinus thrombosis
      (CVST). METHODS: 100 patients with CVST were included in the study. The
      occurrence of acute seizures was noted. The predictors of acute seizure were
      evaluated by univariate analysis including the demographic (gender, age),
      clinical (headache, focal neurological deficit, papilloedema, GCS score), type
      and number of risk factors, MRI findings (Type of lesion: hemorrhagic infarction
      or hematoma, location of lesion) and MRV findings (superficial or deep sinus,
      cortical veins). RESULTS: A total of 46 patients had acute seizures. On
      univariate analysis, altered mental status (p<0.001), paresis (p=0.03), GCS score
      <8 (p=0.009), hemorrhagic infarct on imaging (p=0.04), involvement of frontal
      lobe (p=0.02), superior sagittal sinus (p=0.008), and high D-dimer levels
      (p=0.03) were significantly associated with acute seizure. On multivariate
      analysis, the hemorrhagic infarct on MRI and high D-dimer was independently
      predictive for early seizure. CONCLUSION: The predictive factors for the acute
      seizures are altered mental status (GCS<8), focal deficits, hemorrhagic infarct,
      involvement of frontal lobe and superior sagittal sinus with high D-dimer levels.

PMID- 27023400
TI  - A comparison of salivary IgA in children with Down syndrome and their family
      members.
AB  - The aim of this study was to compare total IgA in the whole saliva of children
      with Down syndrome with levels in sibling and parent groups. IgA measurements
      were presented as the concentration in saliva (MUg/ml) and also adjusted for
      salivary flow rate (SFR; MUg/min). Twenty children with Down syndrome, ten
      siblings and twenty parents were recruited. Stimulated whole saliva was collected
      from the participants and SFR calculated. The measurement of salivary IgA (sIgA)
      was carried out using an indirect competitive Enzyme-Linked Immunosorbent Assay.
      The difference in the mean SFR between children with Down syndrome, parents and
      siblings were not statistically significant. The mean salivary concentration of
      IgA was higher in children with Down syndrome (95.1 MUg/ml) compared with
      siblings (48.3 MUg/ml; p=0.004). When adjusted for SFR children with Down
      syndrome had mean sIgA levels of 98.8 MUg/min and the siblings 48.6 MUg/min
      (p=0.008). The children with Down syndrome had sIgA levels similar to those of
      the parents (92.5 MUg/ml; 93.2 MUg/min). There was a positive correlation between
      age and sIgA concentration in the siblings (p=0.008) but not for children with
      Down syndrome (p=0.363). This suggests that under similar environmental
      influences, the levels of sIgA in children with Down syndrome are higher than in
      the siblings, from a very young age.

PMID- 27023401
TI  - Evaluation of antibiofilm and mechanical properties of new nanocomposites based
      on acrylic resins and silver vanadate nanoparticles.
AB  - OBJECTIVE: The purpose of this study was evaluate, for the first time, the impact
      of incorporation of nanostructured silver vanadate (beta-AgVO3) in antibiofilm
      and mechanical properties of dental acrylic resins (poly(methyl methacrylate),
      PMMA). DESIGN: The beta-AgVO3 was synthesized and characterized by X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning
      electron microscopy, and microanalysis (SEM/EDS). Resins specimens were prepared
      with 0-10% wt.% beta-AgVO3 and characterized by SEM, XRD and optical microscopy.
      The antibiofim activity of the samples against Candida albicans and Streptococcus
      mutans was investigated by XTT reduction test, colony-forming units (CFUs), and
      confocal laser scanning microscopy (CLSM). The flexural strength, hardness, and
      surface roughness of the samples containing beta-AgVO3 were compared with the
      pure PMMA matrix. RESULTS: The incorporation of 10% beta-AgVO3 significantly
      reduced the metabolic activity of C. albicans and S. mutans (p<0.05). There was a
      reduction in microbial load (CFU/mL) of microorganisms for the different
      concentrations used (p<0.05), which was confirmed by confocal microscopy. The
      addition of beta-AgVO3 did not change the mechanical properties of hardness and
      surface roughness of the resins (p>0.05). However, flexural strength decreased
      with the addition of amounts greater than 1% (p<0.05). CONCLUSIONS: beta-AgVO3
      additions in dental acrylic resin may have an impact on inhibition of biofilm of
      main microorganisms associated with dental prostheses. However, the viability of
      clinical use should be evaluated in function of changed promoted in some
      mechanical properties.

PMID- 27023402
TI  - In vivo studies of effects of antidepressants on parotid salivary secretion in
      the rat.
AB  - Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while
      antidepressants such as selective serotonin reuptake inhibitors (SSRI) are
      considered less xerogenic. The antimuscarinic effect of the TCAs has been
      considered to be the principal mechanism causing a dry mouth. Although the
      muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the
      salivation reflex arc may be affected at other levels as well. We currently
      wondered whether or not antidepressants exert an inhibition of the salivary
      reflex not only at the glandular level but at a central level as well. In this
      study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin
      noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex-
      (0.5M citric acid applied on the tongue) and methacholine-evoked salivary
      secretion. While all three compounds inhibited citric acid-evoked secretion (-40
      to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited
      methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both
      citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to
      49%). This was particularly obvious for the salivary protein output (>200%). In
      the presence of alpha- and beta-adrenoceptor antagonists, the citalopram- and
      venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of
      type may exert xerogenic effects by inhibiting the salivary reflex in the central
      nervous system. However, while TCAs may also hamper the secretory response by
      antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to
      lack this additional xerogenic mechanism indicating a better therapeutic profile
      and better opportunities for pharmacological treatment of drug-induced
      xerostomia. 

PMID- 27023404
TI  - Probiotics for prevention of necrotizing enterocolitis and sepsis in preterm
      infants.
AB  - PURPOSE OF REVIEW: Few areas in neonatal medicine have generated as much
      discussion and controversy as the use of prophylactic probiotics for the
      prevention of necrotizing enterocolitis. We summarize recent studies from the
      last 1-2 years. RECENT FINDINGS: Systematic reviews show that probiotics reduce
      the risk of necrotizing enterocolitis but there are methodological limitations to
      all the published trials, and the largest trial to date is at odds with the
      conclusions of the meta-analyses. Trials have used a range of commercially
      available products with differing species, and administered these at different
      times to heterogeneous populations of preterm babies. Although there is strong
      evidence to show that 'probiotics' are likely to represent a major advance for
      neonatal care, it is increasingly clear that not all species have beneficial
      effects in preterm infants. This makes interpretation of meta-analyses complex,
      and the determination of a single 'risk reduction' potentially flawed. SUMMARY:
      Despite current uncertainties, it is difficult for clinicians to ignore the
      current data, and increasing numbers now use commercially available products. It
      remains a matter of concern that many products lack the robust quality control
      most clinicians and parents would consider important for use in vulnerable
      populations. Head-to-head trials are needed.

PMID- 27023405
TI  - Teaching psychomotor skills in the twenty-first century: Revisiting and reviewing
      instructional approaches through the lens of contemporary literature.
AB  - A diverse range of health professionals use psychomotor skills as part of their
      professional practice roles. Most health disciplines use large or complex
      psychomotor skills. These skills are first taught by the educator then acquired,
      performed, and lastly learned. Psychomotor skills may be taught using a variety
      of widely-accepted and published teaching models. The number of teaching steps
      used in these models varies from two to seven. However, the utility of these
      models to teach skill acquisition and skill retention are disputable when
      teaching complex skills, in contrast to simple skills. Contemporary motor
      learning and cognition literature frames instructional practices which may assist
      the teaching and learning of complex task-based skills. This paper reports 11
      steps to be considered when teaching psychomotor skills.

PMID- 27023403
TI  - Hepatitis B Virus Stimulated Fibronectin Facilitates Viral Maintenance and
      Replication through Two Distinct Mechanisms.
AB  - Fibronectin (FN) is a high molecular weight extracellular matrix protein that
      functions in cell adhesion, growth, migration, and embryonic development.
      However, little is known about the role of FN during viral infection. In the
      present study, we found significantly higher levels of FN in sera, and liver
      tissues from hepatitis B virus (HBV) patients relative to healthy individuals.
      HBV expression enhanced FN mRNA and protein levels in the hepatic cell lines Huh7
      and HepG2. HBV infection of susceptible HepG2-sodium taurocholate co-transporting
      polypeptide cells also increased FN expression. We also found that
      transcriptional factor specificity protein 1 was involved in the induction of FN
      by HBV. Knockdown of FN expression significantly inhibited HBV DNA replication
      and protein synthesis through activating endogenous IFN-alpha production. In
      addition, FN interacted with the transforming growth factor beta-activated
      protein kinase 1 (TAK1) and TAK1-binding protein complex and attenuated
      interferon signaling by inhibiting TAK1 phosphorylation. Furthermore, the nuclear
      translocation of NF-kappaB/p65 was found to be inhibited by FN. We also observed
      that FN promoted HBV enhancers to support HBV expression. These results suggest
      novel functions of endogenous FN involved in immune evasion and maintenance of
      HBV replication. 

PMID- 27023406
TI  - Letter to the Editor: Author Response.

PMID- 27023407
TI  - Pain and discomfort following insertion of miniscrews and premolar extractions: A
      randomized controlled trial.
AB  - OBJECTIVE: To investigate and compare the experience of pain and discomfort
      between insertion of miniscrews and premolar extractions in adolescent patients.
      MATERIALS AND METHODS: A total of 80 adolescents were recruited and randomized
      into groups A and B. Both groups were treated with extraction of the upper first
      premolars and fixed appliance. Beyond the fixed appliance, patients in group A
      received anchorage reinforcement with miniscrews. Miniscrews were inserted
      buccally between the second premolar and first molar when space closure started.
      Space closure was performed as en masse retraction with immediate loading by 150
      g coil springs. Pain, discomfort, impact on daily activities, and functional jaw
      impairment were assessed with patient-reported questionnaires. Questionnaires
      were filled in at baseline, the evening after tooth extraction, 1 week after
      tooth extraction, the evening after screw placement, and 1 week after screw
      placement. RESULTS: Patients reported significantly lower levels of pain (P <
      .001) and discomfort (P = .012) after screw placement compared with premolar
      extractions. The ability to drink (P = .035) and the ability to take a big bite
      (P < .001) were also significantly less disturbed in the evening after screw
      placement. During the first week after screw placement, the impact on leisure
      time activities was significantly lower (P = .015) compared with premolar
      extractions. CONCLUSION: The use of miniscrews in adolescents can be recommended
      from a pain and discomfort perspective.

PMID- 27023408
TI  - Reproducibility and reliability of three-dimensional soft tissue landmark
      identification using three-dimensional stereophotogrammetry.
AB  - OBJECTIVE: To evaluate the intraexaminer repeatability and interexaminer
      reproducibility of soft tissue landmarks on three-dimensional (3-D)
      stereophogrammetric images. MATERIALS AND METHODS: Thirty-four
      stereophotogrammetric images were taken and 19 soft tissue points were
      identified. The images were obtained using the 3-DMD Face (3-DMD TM Ltd, Atlanta,
      Ga) system. Two examiners marked 34 images manually with a mouse-driven cursor 4
      weeks apart. Intraexaminer marking differences were calculated and classified as
      <0.5 mm, 0.5-1 mm, and >1 mm. Intraclass correlation coefficients were calculated
      for intraexaminer reliability. A paired-samples t-test was used to evaluate the
      difference between the examiners. Interexaminer reproducibility was evaluated by
      kappa analysis. Statistical significance was set at P < .05. RESULTS: Only one
      landmark (labiale superior) had an intraexaminer marking difference less than 0.5
      mm. Existing landmarks had an intraexaminer difference less than 1 mm, but higher
      than 0.5 mm. The intraclass correlation coefficients (ICCs) indicated good
      intraexaminer repeatability for both observers. The ICC range for examiners 1 and
      2 was 0.986-1.000 and 0.990-1.000, respectively. Kappa scores showed good
      interexaminer agreement, especially on the z-axis. CONCLUSIONS: Except labiale
      superior, the soft tissue landmarks used in this study were shown to have
      moderate reproducibility, but the difference between the landmarks was less than
      1 mm, and they had clinically acceptable reproducibility.

PMID- 27023409
TI  - Fostering strategies in materials design.

PMID- 27023410
TI  - Fixed Rehabilitation of Edentulous Mandibles Using 2 to 4 Implants: A Systematic
      Review.
AB  - OBJECTIVE: This systematic review evaluated survival rates, marginal bone loss
      (MBL), and complications of using 2 to 4 implants to support full-arch fixed
      prostheses in the mandible. MATERIALS AND METHODS: An electronic search was
      performed in PubMed, Web of Science, and the Cochrane Central Register of
      Controlled Trials to identify relevant articles published until March 2015.
      Articles were critically reviewed to determine the level of quality. RESULTS: The
      initial search resulted in 910 articles from PubMed/MEDLINE, 162 titles from the
      Cochrane Central Register of Controlled Trials, and 363 from the Web of Science.
      After an initial assessment and careful reading, 19 studies published between
      1999 and 2014 were included in this review. CONCLUSIONS: The results of this
      review suggest that full-arch fixed dental prosthesis in mandible supported by 2
      to 4 implants exhibited a low rate of failures for implants and prostheses, a low
      rate of MBL, and a low rate of biomechanical and biological complications.

PMID- 27023411
TI  - Assessment of the effectiveness of head only and back-of-the-head electrical
      stunning of chickens.
AB  - The study assesses the effectiveness of reversible head-only and back-of-the-head
      electrical stunning of chickens using 130-950 mA per bird at 50 Hz AC. Three
      trials were conducted to compare both stunning systems: (a) behavioural
      assessment of return of consciousness, (b) insensibility to thermal pain, and (c)
      assessment of return of brain activity with visually evoked potentials (VEPs).
      Assessment of behaviour suggested that the period of unconsciousness following
      head-only electrical stunning was shorter in hens compared to broilers. Stunning
      across the back-of-the-head delayed the time to return of brainstem function
      compared to stunning with standard head-only electrodes. Additionally, back-of
      the-head stunning produced a more prolonged period of electroanalgesia compared
      to head-only. Based on examination of return of brain function with VEPs in hens,
      back-of-the-head stunning produced a shorter-lasting stun than standard head
      only. However, even for standard head-only, the stun was notably shorter than
      previously reported. In some birds, brain function had returned within 9 s after
      the end of stunning. The results suggest that some birds may recover
      consciousness prior to or during the neck cut. Based on these findings, back-of
      the-head stunning and standard head-only stunning of hens should not be
      recommended without further development. 

PMID- 27023412
TI  - Door Opening Affects Operating Room Pressure During Joint Arthroplasty.

PMID- 27023414
TI  - Precision Medicine: A New Frontier in Spine Surgery.

PMID- 27023413
TI  - Does Intraoperative Fluoroscopy Improve Component Positioning in Total Hip
      Arthroplasty?

PMID- 27023415
TI  - Early Experience and Initial Outcomes With Patient-Specific Spine Rods for Adult
      Spinal Deformity.
AB  - The objectives of this study were to describe the process of preoperative
      planning and using patient-specific rods. This retrospective case series involved
      18 patients with adult spinal deformity who were treated with posterior
      instrumentation and spine fusion, with lumbar or thoracic osteotomies, using
      patient-specific rods. Data extracted included demographic/surgical variables and
      preoperative, predicted (surgical plan), and postoperative spinopelvic
      parameters. The outcome analysis involved assessment of preoperative, planned,
      and postoperative variables. Treatment effect evaluation involved assessing
      differences between preoperative and postoperative values and correspondence
      between planned and achieved results. Surgery using preoperative planned patient
      specific rods led to excellent adult spinal deformity correction and spinopelvic
      alignment.

PMID- 27023416
TI  - Sacroiliac Joint Treatment Personalized to Individual Patient Anatomy Using 3
      Dimensional Navigation.
AB  - During the past 10 years, the sacroiliac (SI) joint has evolved from being barely
      recognized as a source of pain, to being a joint treated only nonsurgically or
      with great surgical morbidity, to currently being a joint treated with minimally
      invasive techniques that are personalized to the individual patient. The complex
      3-dimensional anatomy of the SI joint and lack of parallel to traditional imaging
      planes requires a thorough understanding of the structures within and around the
      SI joint that may be at risk of injury. Thus, the SI joint is ideally suited for
      intraoperative 3-dimensional imaging and surgical navigation when being treated
      minimally invasively.

PMID- 27023417
TI  - Patient-Specific Templating of Lumbar Total Disk Replacement to Restore Normal
      Anatomy and Function.
AB  - The purpose of this study was to develop a tool to determine optimal placement
      and size for total disk replacements (TDRs) to improve patient outcomes of pain
      and function. The authors developed a statistical shape model to determine the
      anatomical variables that influence the placement, function, and outcome of
      lumbar TDR. A patient-specific finite element analysis model has been developed
      that is now used prospectively to identify patients suitable for TDR and to
      create a surgical template to facilitate implant placement to optimize range of
      motion and clinical outcomes. Patient factors and surgical techniques that
      determine success regarding function and pain are discussed in this article.

PMID- 27023419
TI  - The effect of local vs remote experimental pain on motor learning and
      sensorimotor integration using a complex typing task.
AB  - Recent work demonstrated that capsaicin-induced acute pain improved motor
      learning performance; however, baseline accuracy was very high, making it
      impossible to discern the impact of acute pain on motor learning and retention.
      In addition, the effects of the spatial location of capsaicin application were
      not explored. Two experiments were conducted to determine the interactive effects
      of acute pain vs control (experiment 1) and local vs remote acute pain
      (experiment 2) on motor learning and sensorimotor processing. For both
      experiments, somatosensory evoked potential (SEP) amplitudes and motor learning
      acquisition and retention (accuracy and response time) data were collected at
      baseline, after application, and after motor learning. Experiment 1: N11 (P <
      0.05), N13 (P < 0.05), and N30 (P < 0.05) SEP peak amplitudes increased after
      motor learning in both groups, whereas the N20 SEP peak increased in the control
      group (P < 0.05). At baseline, the intervention group outperformed the control
      group in accuracy (P < 0.001). Response time improved after motor learning (P <
      0.001) and at retention (P < 0.001). Experiment 2: The P25 SEP peak decreased in
      the local group after application of capsaicin cream (P < 0.01), whereas the N30
      SEP peaks increased after motor learning in both groups (P < 0.05). Accuracy
      improved in the local group at retention (P < 0.005), and response time improved
      after motor learning (P < 0.005) and at retention (P < 0.001). This study
      suggests that acute pain may increase focal attention to the body part used in
      motor learning, contributing to our understanding of how the location of pain
      impacts somatosensory processing and the associated motor learning.

PMID- 27023418
TI  - Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.
AB  - Although animal models have consistently demonstrated acute pain inhibitory
      effects of nicotine and tobacco, human experimental studies have yielded mixed
      results. The main goal of this meta-analysis was to quantify the effects of
      nicotine/tobacco administration on human experimental pain threshold and
      tolerance ratings. A search of PubMed and PsycINFO online databases identified 13
      eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15
      tests of pain threshold (N = 339). Meta-analytic integration for both threshold
      and tolerance outcomes revealed that nicotine administered through tobacco smoke
      and other delivery systems (eg, patch, nasal spray) produced acute analgesic
      effects that may be characterized as small to medium in magnitude (Hedges g =
      0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates
      remained significant and indicated that these effects may be closer to small. Sex
      composition was observed to be a significant moderator, such that pain threshold
      effects were more robust among samples that included more men than women. These
      results help to clarify a mixed literature and may ultimately help to inform the
      treatment of both pain and nicotine dependence. Pain and tobacco smoking are both
      highly prevalent and comorbid conditions. Current smoking has been associated
      with more severe chronic pain and physical impairment. Acute nicotine-induced
      analgesia could make smoking more rewarding and harder to give up. Future
      research should use dynamic measures of experimental pain reactivity and further
      explore biopsychosocial mechanisms of action.

PMID- 27023422
TI  - Complex regional pain syndrome: evidence for warm and cold subtypes in a large
      prospective clinical sample.
AB  - Limited research suggests that there may be Warm complex regional pain syndrome
      (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most
      strongly to the former. This study for the first time used an unbiased
      statistical pattern recognition technique to evaluate whether distinct Warm vs
      Cold CRPS subtypes can be discerned in the clinical population. An international,
      multisite study was conducted using standardized procedures to evaluate signs and
      symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up
      evaluations in 112 of these patients. Two-step cluster analysis using automated
      cluster selection identified a 2-cluster solution as optimal. Results revealed a
      Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty
      extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less
      edematous extremity. Median pain duration was significantly (P < 0.001) shorter
      in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with
      pain intensity comparable. A derived total inflammatory score was significantly
      (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline
      but diminished significantly (P < 0.001) over the follow-up period, whereas this
      score did not diminish in the Cold CRPS group (time * subtype interaction: P <
      0.001). Results support the existence of a Warm CRPS subtype common in patients
      with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most
      common in chronic CRPS. The pattern of clinical features suggests that
      inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but
      that these mechanisms diminish substantially during the first year postinjury.

PMID- 27023423
TI  - What the brain tells the spinal cord.

PMID- 27023420
TI  - The musculoskeletal diagnosis cohort: examining pain and pain care among
      veterans.
AB  - Musculoskeletal disorders (MSDs) are highly prevalent, painful, and costly
      disorders. The MSD Cohort was created to characterize variation in pain,
      comorbidities, treatment, and outcomes among patients with MSD receiving Veterans
      Health Administration care across demographic groups, geographic regions, and
      facilities. We searched electronic health records to identify patients treated in
      Veterans Health Administration who had ICD-9-CM codes for diagnoses including,
      but not limited to, joint, back, and neck disorders, and osteoarthritis. Cohort
      inclusion criteria were 2 or more outpatient visits occurring within 18 months of
      one another or one inpatient visit with an MSD diagnosis between 2000 and 2011.
      The first diagnosis is the index date. Pain intensity numeric rating scale (NRS)
      scores, comorbid medical and mental health diagnoses, pain-related treatments,
      and other characteristics were collected retrospectively and prospectively. The
      cohort included 5,237,763 patients; their mean age was 59, 6% were women, 15%
      identified as black, and 18% reported severe pain (NRS >= 7) on the index date.
      Nontraumatic joint disorder (27%), back disorder (25%), and osteoarthritis (21%)
      were the most common MSD diagnoses. Patients entering the cohort in recent years
      had more concurrent MSD diagnoses and higher NRS scores. The MSD Cohort is a rich
      resource for collaborative pain-relevant health service research.

PMID- 27023421
TI  - Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor:
      implications for migraine.
AB  - Migraine is a painful neurologic disorder with premonitory symptomatology that
      can include disturbed appetite. Migraine pathophysiology involves abnormal
      activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is
      synthesized in the brain and is involved in pain modulation. NPY receptors are
      present in trigeminal ganglia and trigeminal nucleus caudalis suggesting a role
      in migraine pathophysiology. The present study aimed to determine the effect of
      systemic administration of NPY on TCC neuronal activity in response to dural
      nociceptive trigeminovascular activation. We performed in vivo electrophysiology
      in anesthetized rats, administered NPY (10, 30, and 100 ug.kg), and investigated
      the receptors involved by studying NPY Y1 (30 ug.kg), Y2 (30 ug.kg), and Y5
      receptor agonists (100.ug.kg), and NPY Y1 receptor antagonist (30 ug.kg). NPY (30
      and 100 ug.kg) significantly reduced TCC neuronal firing in response to dural
      evoked trigeminovascular activation, but only NPY (30 ug.kg) significantly
      reduced spontaneous trigeminal firing. NPY Y1 receptor agonist also significantly
      reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 ug.kg), NPY Y2,
      and Y5 receptor agonists, and the NPY Y1 receptor antagonist had no significant
      effects on nociceptive dural-evoked neuronal firing in the TCC or spontaneous
      trigeminal firing. This study demonstrates that NPY dose dependently inhibits
      dural-evoked trigeminal activity, through NPY Y1 receptor activation, indicating
      antinociceptive actions of NPY in a migraine animal model. Based on the role of
      NPY in appetite regulation, it is possible that disruption of the NPY system
      might explain changes of appetite in migraineurs.

PMID- 27023424
TI  - Therapeutic potential of RQ-00311651, a novel T-type Ca2+ channel blocker, in
      distinct rodent models for neuropathic and visceral pain.
AB  - T-type Ca channels (T channels), particularly Cav3.2 among the 3 isoforms, play a
      role in neuropathic and visceral pain. We thus characterized the effects of RQ
      00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human
      Cav3.1 or Cav3.2 by electrophysiological and fluorescent Ca signaling assays, and
      also evaluated the antiallodynic/antihyperalgesic activity of RQ in somatic,
      visceral, and neuropathic pain models in rodents. RQ-00311651 strongly suppressed
      T currents when tested at holding potentials of -65 ~ -60 mV, but not -80 mV, in
      the Cav3.1- or Cav3.2-expressing cells. RQ-00311651 also inhibited high K-induced
      Ca signaling in those cells. In mice, RQ, administered intraperitoneally (i.p.)
      at 5 to 20 mg/kg or orally at 20 to 40 mg/kg, significantly suppressed the
      somatic hyperalgesia and visceral pain-like nociceptive behavior/referred
      hyperalgesia caused by intraplantar and intracolonic administration of NaHS or
      Na2S, H2S donors, respectively, which involve the enhanced activity of Cav3.2
      channels. RQ-00311651, given i.p. at 5 to 20 mg/kg, exhibited antiallodynic or
      antihyperalgesic activity in rats with spinal nerve injury-induced neuropathy or
      in rats and mice with paclitaxel-induced neuropathy. Oral and i.p. RQ at 10 to 20
      mg/kg also suppressed the visceral nociceptive behavior and/or referred
      hyperalgesia accompanying cerulein-induced acute pancreatitis and
      cyclophosphamide-induced cystitis in mice. The analgesic and
      antihyperalgesic/antiallodynic doses of oral and i.p. RQ did not significantly
      affect the locomotor activity and motor coordination. Together, RQ is considered
      a state-dependent blocker of Cav3.1/Cav3.2 T channels and may serve as an orally
      available analgesic for treatment of neuropathic and inflammatory pain including
      distinct visceral pain with minimum central side effects.

PMID- 27023425
TI  - Relieving pain using dose-extending placebos: a scoping review.
AB  - Placebos are often used by clinicians, usually deceptively and with little
      rationale or evidence of benefit, making their use ethically problematic. In
      contrast with their typical current use, a provocative line of research suggests
      that placebos can be intentionally exploited to extend analgesic therapeutic
      effects. Is it possible to extend the effects of drug treatments by interspersing
      placebos? We reviewed a database of placebo studies, searching for studies that
      indicate that placebos given after repeated administration of active treatments
      acquire medication-like effects. We found a total of 22 studies in both animals
      and humans hinting of evidence that placebos may work as a sort of dose extender
      of active painkillers. Wherever effective in relieving clinical pain, such
      placebo use would offer several advantages. First, extending the effects of a
      painkiller through the use of placebos may reduce total drug intake and side
      effects. Second, dose-extending placebos may decrease patient dependence. Third,
      using placebos along with active medication, for part of the course of treatment,
      should limit dose escalation and lower costs. Provided that nondisclosure is
      preauthorized in the informed consent process and that robust evidence indicates
      therapeutic benefit comparable to that of standard full-dose therapeutic
      regimens, introducing dose-extending placebos into the clinical arsenal should be
      considered. This novel prospect of placebo use has the potential to change our
      general thinking about painkiller treatments, the typical regimens of painkiller
      applications, and the ways in which treatments are evaluated.

PMID- 27023426
TI  - Archimedean Tilings and Hierarchical Lamellar Morphology Formed by
      Semicrystalline Miktoarm Star Terpolymer Thin Films.
AB  - 3-Miktoarm star terpolymer architecture provides a window of opportunity in the
      design of complex "three-colored" patterns at the nanometer scale. Here, the
      directed self-assembly (DSA) of 3-miktoarm star terpolymer (poly(1,1-dimethyl
      silacyclobutane)-arm-polystyrene-arm-poly(d,l-lactide acid)) (PDMSB-arm-PS-arm
      PLA, noted hereafter 3 MU-DSL) into a hierarchical lamellar morphology is
      described. Excellent orientational order has been achieved by templating the
      asymmetric hierarchical lamellar morphology with topographical substrates.
      Increasing the PLA volume fraction leads to the formation of a hexagonal [6.6.6]
      Archimedean tiling which coexists with a metastable square symmetry [4.8.8]
      tiling stabilized by the step between terraces. Stability of the [6.6.6] tiling
      over the [4.8.8] one is also demonstrated with GISAXS measurements.

PMID- 27023427
TI  - Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation
      Is State-Dependent.
AB  - Cortical oscillations play a fundamental role in organizing large-scale
      functional brain networks. Noninvasive brain stimulation with temporally
      patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS)
      and transcranial alternating current stimulation (tACS) have been proposed to
      modulate these oscillations. Thus, these stimulation modalities represent
      promising new approaches for the treatment of psychiatric illnesses in which
      these oscillations are impaired. However, the mechanism by which periodic brain
      stimulation alters endogenous oscillation dynamics is debated and appears to
      depend on brain state. Here, we demonstrate with a static model and a neural
      oscillator model that recurrent excitation in the thalamo-cortical circuit,
      together with recruitment of cortico-cortical connections, can explain the
      enhancement of oscillations by brain stimulation as a function of brain state. We
      then performed concurrent invasive recording and stimulation of the human
      cortical surface to elucidate the response of cortical oscillations to periodic
      stimulation and support the findings from the computational models. We found that
      (1) stimulation enhanced the targeted oscillation power, (2) this enhancement
      outlasted stimulation, and (3) the effect of stimulation depended on behavioral
      state. Together, our results show successful target engagement of oscillations by
      periodic brain stimulation and highlight the role of nonlinear interaction
      between endogenous network oscillations and stimulation. These mechanistic
      insights will contribute to the design of adaptive, more targeted stimulation
      paradigms. 

PMID- 27023430
TI  - Clinical Nursing Skills - DVD with Workbook Nicol Maggie (Ed) Clinical Nursing
      Skills - DVD with Workbook 160pp Mosby 0 7234 3384 4 0007181671.
AB  - This package aims to support the nursing student in acquiring fundamental nursing
      skills. The intention is to teach the practical skill, its rationale and the
      related biological principles.

PMID- 27023429
TI  - Practice Development in Nursing McCormack Brendan et al Practice Development in
      Nursing 352pp Blackwell Publishing 9781405110389 1405110384.
AB  - Divided into two parts, the first seven chapters deal with conceptual elements
      that impact upon, or have relative sequence to, processes of change, theories of
      culture and positive attitudes towards the complexity of professional and
      personal development.

PMID- 27023428
TI  - Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral
      Integration Sites.
AB  - Retroviruses exhibit signature integration preferences on both the local and
      global scales. Here, we present a detailed protocol for (1) generation of diverse
      libraries of retroviral integration sites using ligation-mediated PCR (LM-PCR)
      amplification and next-generation sequencing (NGS), (2) mapping the genomic
      location of each virus-host junction using BEDTools, and (3) analyzing the data
      for statistical relevance. Genomic DNA extracted from infected cells is
      fragmented by digestion with restriction enzymes or by sonication. After suitable
      DNA end-repair, double-stranded linkers are ligated onto the DNA ends, and semi
      nested PCR is conducted using primers complementary to both the long terminal
      repeat (LTR) end of the virus and the ligated linker DNA. The PCR primers carry
      sequences required for DNA clustering during NGS, negating the requirement for
      separate adapter ligation. Quality control (QC) is conducted to assess DNA
      fragment size distribution and adapter DNA incorporation prior to NGS. Sequence
      output files are filtered for LTR-containing reads, and the sequences defining
      the LTR and the linker are cropped away. Trimmed host cell sequences are mapped
      to a reference genome using BLAT and are filtered for minimally 97% identity to a
      unique point in the reference genome. Unique integration sites are scrutinized
      for adjacent nucleotide (nt) sequence and distribution relative to various
      genomic features. Using this protocol, integration site libraries of high
      complexity can be constructed from genomic DNA in three days. The entire protocol
      that encompasses exogenous viral infection of susceptible tissue culture cells to
      integration site analysis can therefore be conducted in approximately one to two
      weeks. Recent applications of this technology pertain to longitudinal analysis of
      integration sites from HIV-infected patients. 

PMID- 27023431
TI  - Bowel Cancer: Foundations for Practice Borwell Barbara Bowel Cancer: Foundations
      for Practice 240pp Whurr Publishers 9781861564528 186156452X.
AB  - While the majority of contributors are nurses, this book offers a
      multidisciplinary perspective on the impact of this disease and its treatment for
      foundation level students.

PMID- 27023432
TI  - Indole Synthesis via Cobalt(III)-Catalyzed Oxidative Coupling of N-Arylureas and
      Internal Alkynes.
AB  - A mild Co(III)-catalyzed oxidative annulation of N-arylureas and internal alkynes
      has been developed. The use of less electrophilic ureas other than acetamides as
      directing groups is crucial for the reaction. A broad range of synthetically
      useful functional groups are compatible with this reaction, thus providing a new
      opportunity for the synthesis of diverse indoles. 

PMID- 27023433
TI  - Leucocyte Membrane-Coated Janus Microcapsules for Enhanced Photothermal Cancer
      Treatment.
AB  - Polyelectrolyte multilayer (PEM) capsules are promising candidates for many kinds
      of cancer detection and treatment but are usually intended to deliver cargo to
      specific sites or to destroy cancer cells based on photothermal effects from the
      outside. In this publication we prove that it is possible to kill cancer cells
      from the inside based on phagocytosed PEM capsules. In addition we show how to
      open the cells and bring the PEM capsules to the surface of cancer cells based on
      photothermal effects and rapid evaporation of water. Diffusion-based temperature
      determinations of the photothermal effect up to the evaporation temperature of
      water are presented. 

PMID- 27023434
TI  - Elasticity of randomly diluted honeycomb and diamond lattices with bending
      forces.
AB  - We use numerical simulations and an effective-medium theory to study the rigidity
      percolation transition of the honeycomb and diamond lattices when weak bond
      bending forces are included. We use a rotationally invariant bond-bending
      potential, which, in contrast to the Keating potential, does not involve any
      stretching. As a result, the bulk modulus does not depend on the bending
      stiffness kappa. We obtain scaling functions for the behavior of some elastic
      moduli in the limits of small DeltaP = 1-P, and small deltaP = P-Pc, where P is
      an occupation probability of each bond, and Pc is the critical probability at
      which rigidity percolation occurs. We find good quantitative agreement between
      effective-medium theory and simulations for both lattices for P close to one.

PMID- 27023435
TI  - Association Analysis of Polymorphisms in TOMM40, CR1, PVRL2, SORL1, PICALM, and
      14q32.13 Regions in Colombian Alzheimer Disease Patients.
AB  - OBJECTIVE: We evaluated the association of several single-nucleotide
      polymorphisms in different genes including APOE, TOMM40, CR1, PVRL2, SORL1,
      PICALM, and GWA_14q32.13 in a Colombian sample of Late-Onset Alzheimer disease
      (LOAD) patients. METHODS: A case-control study was conducted in 362 individuals
      (181 LOADs and 181 controls) to determine the association of single-nucleotide
      polymorphisms in APOE (e2, e3, and e4), TOMM40 (rs2075650), CR1 (rs665640), PVRL2
      (rs6859), SORL1 (rs11218304), PICALM (rs3851179), and GWA_14q32.13 (rs11622883)
      with LOAD in a sample from Colombia. RESULTS: We were able to confirm the
      previously reported association of the APOE4 allele with AD. In addition, we
      report a new significant association with rs2075650 of TOMM40 for LOAD in our
      sample. We did not detect any significant interaction between TOMM40 and APOE4
      carriers (heterozygous or homozygous) for disease risk development. However,
      Kaplan-Meier survival analyses suggest that AD patients with TOMM40 allele
      rs2075650-G have an average age of disease onset of 6 years earlier compared with
      carriers of the A allele. In addition, the age of disease onset is earlier if
      APOE4/4 is present. CONCLUSION: Our findings suggest that rs2075650 of TOMM40
      could be involved in earlier presentation of LOAD in the Colombian population.

PMID- 27023436
TI  - Aberrant Methylation of the E-Cadherin Gene Promoter Region in Endometrium and
      Ovarian Endometriotic Cysts of Patients with Ovarian Endometriosis.
AB  - The loss of E-cadherin expression plays an important role in the development of
      endometriosis, but the molecular mechanism is not clear to date. It has been
      confirmed that the hypermethylation of the CpG island may be an important
      molecular mechanism in the transcriptional inactivation of E-cadherin gene (CDH1)
      in many cancers. The present study investigated the methylation status of CDH1
      promoter region in ovarian endometriotic cysts and the endometrium of women with
      ovarian endometriosis. The results showed that the frequency of CDH1 promoter
      methylation in eutopic (26%), ectopic tissues (32%) of women with ovarian
      endometriosis was significantly higher than that of endometrium tissue of women
      without endometriosis (8%). Further, results of the study showed that the
      expression level of mRNA and protein of E-cadherin in methylation-positive
      tissues was significantly lower than that in methylation-negative tissues (p =
      0.023 and 0.035, respectively). Pearson's correlation coefficients analysis
      showed the level of CDH1 mRNA expression was closely related to the level of E
      cadherin protein expression. The results implied that the aberrant methylation of
      the CDH1 promoter region in the endometrium of the women may contribute, at least
      in part, to the development of ovarian endometriosis.

PMID- 27023437
TI  - Possible biomarkers modulating haloperidol efficacy and/or tolerability.
AB  - Haloperidol (HP) is widely used in the treatment of several forms of psychosis.
      Despite of its efficacy, HP use is a cause of concern for the elevated risk of
      adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary
      across subjects, indicating the involvement of several factors in HP mechanism of
      action. The use of biomarkers that could monitor or even predict HP treatment
      impact would be of extreme importance. We reviewed the elements that could
      potentially be used as peripheral biomarkers of HP effectiveness. Although a
      validated biomarker still does not exist, we underlined the several potential
      findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which
      could pave the way for future research on HP biomarkers. 

PMID- 27023438
TI  - Surveillance of the Incidence of Non-Communicable Diseases (NCDs) with Sparse
      Resources: A Simulation Study Using Data from a National Diabetes Registry,
      Denmark, 1995-2004.
AB  - We propose two new methods to estimate secular trends in the incidence of a
      chronic disease from a series of prevalence studies and mortality data. One
      method is a direct inversion formula, the second method is a least squares
      estimation. Both methods are validated in a simulation study based on data from a
      diabetes register. The results of the validation show that the proposed methods
      may be useful in epidemiological settings with sparse resources, where running a
      register or a series of follow-up studies is difficult or impossible. 

PMID- 27023439
TI  - Exploring Peptide Ligase Orthologs in Actinobacteria-Discovery of Pseudopeptide
      Natural Products, Ketomemicins.
AB  - We recently identified a novel peptide ligase (PGM1), an ATP-grasp-ligase, that
      catalyzes amide bond formation between (S)-2-(3,5-dihydroxy-4-methoxyphenyl)-2
      guanidinoacetic acid and ribosomally supplied oligopeptides in pheganomycin
      biosynthesis. This was the first example of an ATP-grasp-ligase utilizing
      peptides as nucleophiles. To explore the potential of this type of enzyme, we
      performed a BLAST search and identified many orthologs. The orthologs of
      Streptomyces mobaraensis, Salinispora tropica, and Micromonospora sp. were found
      in similar gene clusters consisting of six genes. To probe the functions of these
      genes, we heterologously expressed each of the clusters in Streptomyces lividans
      and detected novel and structurally similar pseudotripeptides in the broth of all
      transformants. Moreover, a recombinant PGM1 ortholog of Micromonospora sp. was
      demonstrated to be a novel dipeptide ligase catalyzing amide bond formation
      between amidino-arginine and dipeptides to yield tripeptides; this is the first
      report of a peptide ligase utilizing dipeptides as nucleophiles.

PMID- 27023441
TI  - SOBIR1 contributes to non-host resistance to Magnaporthe oryzae in Arabidopsis.
AB  - The rate of entry of Magnaporthe oryzae into Arabidopsis pen2 sobir1 plants was
      significantly higher than that into pen2 plants. The length of the infection
      hyphae in pen2 sobir1 plants was significantly longer than that in pen2 plants.
      These results suggest that SOBIR1 is involved in both penetration and post
      penetration resistance to M. oryzae in Arabidopsis. 

PMID- 27023440
TI  - Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary
      Fibrosis.
AB  - INTRODUCTION: Comorbidities significantly influence the clinical course of
      idiopathic pulmonary fibrosis (IPF). However, their prognostic impact is not
      fully understood. We therefore aimed to determine the impact of comorbidities, as
      individual and as whole, on survival in IPF. METHODS: The database of a tertiary
      referral centre for interstitial lung diseases was reviewed for comorbidities,
      their treatments, their frequency and survival in IPF patients. RESULTS: 272
      patients were identified of which 12% had no, 58% 1-3 and 30% 4-7 comorbidities,
      mainly cardiovascular, pulmonary and oncologic comorbidities. Median survival
      according to the frequency of comorbidities differed significantly with 66 months
      for patients without comorbidities, 48 months when 1-3 comorbidities were
      reported and 35 months when 4-7 comorbidities were prevalent (p = 0.004). A
      multivariate Cox proportional hazard analyses identified other cardiac diseases
      and lung cancer as significant predictors of death, gastro-oesophageal reflux
      disease (GERD) and diastolic dysfunction had a significant positive impact on
      survival. A significant impact of comorbidities associated therapies on survival
      was not discovered. This included the use of proton pump inhibitors at baseline,
      which was not associated with a survival benefit (p = 0.718). We also established
      a predictive tool for highly prevalent comorbidities, termed IPF comorbidome
      which demonstrates a new relationship of IPF and comorbidities. CONCLUSION:
      Comorbidities are frequent in IPF patients. Some comorbidities, especially lung
      cancer, mainly influence survival in IPF, while others such as GERD may inherit a
      more favourable effect. Moreover, their cumulative incidence impacts survival.

PMID- 27023443
TI  - Intermediate Volatility Organic Compound Emissions from On-Road Gasoline Vehicles
      and Small Off-Road Gasoline Engines.
AB  - Dynamometer experiments were conducted to characterize the intermediate
      volatility organic compound (IVOC) emissions from a fleet of on-road gasoline
      vehicles and small off-road gasoline engines. IVOCs were quantified through gas
      chromatography/mass spectrometry analysis of adsorbent samples collected from a
      constant volume sampler. The dominant fraction (>80%, on average) of IVOCs could
      not be resolved on a molecular level. These unspeciated IVOCs were quantified as
      two chemical classes (unspeciated branched alkanes and cyclic compounds) in 11
      retention-time-based bins. IVOC emission factors (mg kg-fuel(-1)) from on-road
      vehicles varied widely from vehicle to vehicle, but showed a general trend of
      lower emissions for newer vehicles that met more stringent emission standards.
      IVOC emission factors for 2-stroke off-road engines were substantially higher
      than 4-stroke off-road engines and on-road vehicles. Despite large variations in
      the magnitude of emissions, the IVOC volatility distribution and chemical
      characteristics were consistent across all tests and IVOC emissions were strongly
      correlated with nonmethane hydrocarbons (NMHCs), primary organic aerosol and
      speciated IVOCs. Although IVOC emissions only correspond to approximately 4% of
      NMHC emissions from on-road vehicles over the cold-start unified cycle, they are
      estimated to produce as much or more SOA than single-ring aromatics. Our results
      clearly demonstrate that IVOCs from gasoline engines are an important class of
      SOA precursors and provide observational constraints on IVOC emission factors and
      chemical composition to facilitate their inclusion into atmospheric chemistry
      models.

PMID- 27023442
TI  - Diffusion Modelling Reveals the Decision Making Processes Underlying Negative
      Judgement Bias in Rats.
AB  - Human decision making is modified by emotional state. Rodents exhibit similar
      biases during interpretation of ambiguous cues that can be altered by affective
      state manipulations. In this study, the impact of negative affective state on
      judgement bias in rats was measured using an ambiguous-cue interpretation task.
      Acute treatment with an anxiogenic drug (FG7142), and chronic restraint stress
      and social isolation both induced a bias towards more negative interpretation of
      the ambiguous cue. The diffusion model was fit to behavioural data to allow
      further analysis of the underlying decision making processes. To uncover the way
      in which parameters vary together in relation to affective state manipulations,
      independent component analysis was conducted on rate of information accumulation
      and distances to decision threshold parameters for control data. Results from
      this analysis were applied to parameters from negative affective state
      manipulations. These projected components were compared to control components to
      reveal the changes in decision making processes that are due to affective state
      manipulations. Negative affective bias in rodents induced by either FG7142 or
      chronic stress is due to a combination of more negative interpretation of the
      ambiguous cue, reduced anticipation of the high reward and increased anticipation
      of the low reward. 

PMID- 27023445
TI  - Clinical Utility of Biomarkers in Localized Prostate Cancer.
AB  - A new generation of prostate cancer (PCa) biomarkers has emerged, including
      diagnostic serum and urine markers aimed at refining the identification high
      grade tumors and tissue-based gene expression assays offering prognostic and
      predictive clinical information. Such tests seek to improve treatment-related
      decisions at multiple decision points, including initial diagnosis and following
      initial primary therapy. In this review, we aim to contextualize the body of
      evidence surrounding these emerging tests, with attention on studies addressing
      clinical utility. 

PMID- 27023444
TI  - An Anti-beta-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of
      Down Syndrome.
AB  - In Down syndrome (DS) or trisomy of chromosome 21, the beta-amyloid (Abeta)
      peptide product of the amyloid precursor protein (APP) is present in excess.
      Evidence points to increased APP gene dose and Abeta as playing a critical role
      in cognitive difficulties experienced by people with DS. Particularly, Abeta is
      linked to the late-life emergence of dementia as associated with
      neuropathological markers of Alzheimer's disease (AD). At present, no treatment
      targets Abeta-related pathogenesis in people with DS. Herein we used a vaccine
      containing the Abeta 1-15 peptide embedded into liposomes together with the
      adjuvant monophosphoryl lipid A (MPLA). Ts65Dn mice, a model of DS, were
      immunized with the anti-Abeta vaccine at 5 months of age and were examined for
      cognitive measures at 8 months of age. The status of basal forebrain cholinergic
      neurons and brain levels of APP and its proteolytic products were measured.
      Immunization of Ts65Dn mice resulted in robust anti-Abeta IgG titers,
      demonstrating the ability of the vaccine to break self-tolerance. The vaccine
      induced antibodies reacted with Abeta without detectable binding to either APP or
      its C-terminal fragments. Vaccination of Ts65Dn mice resulted in a modest, but
      non-significant reduction in brain Abeta levels relative to vehicle-treated
      Ts65Dn mice, resulting in similar levels of Abeta as diploid (2N) mice.
      Importantly, vaccinated Ts65Dn mice showed resolution of memory deficits in the
      novel object recognition and contextual fear conditioning tests, as well as
      reduction of cholinergic neuron atrophy. No treatment adverse effects were
      observed; vaccine did not result in inflammation, cellular infiltration, or
      hemorrhage. These data are the first to show that an anti-Abeta immunotherapeutic
      approach may act to target Abeta-related pathology in a mouse model of DS. 

PMID- 27023446
TI  - Dynamic Risk Stratification in Patients with Differentiated Thyroid Cancer
      Treated Without Radioactive Iodine.
AB  - CONTEXT: Although response to therapy assessment is a validated tool for dynamic
      risk stratification in patients with differentiated thyroid cancer (DTC) treated
      with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not
      been well studied in patients treated with lobectomy or TT without RAI. Because
      these responses to therapy definitions are heavily dependent on serum
      thyroglobulin (Tg) levels, modifications of the original definitions were needed
      to appropriately classify patients treated without RAI. OBJECTIVE: This study
      aimed to validate the response to therapy assessment in patients with DTC treated
      with lobectomy or TT without RAI. DESIGN AND SETTING: This was a retrospective
      study, which took place at a referral center. PATIENTS: A total of 507 adults
      with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They
      had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6%
      intermediate risk. MAIN OUTCOME MEASURE: Main outcome measured was
      recurrent/persistent structural evidence of disease (SED) during a median
      followup period of 100.5 months (24-510). RESULTS: Recurrent/persistent SED was
      observed in 0% of the patients with excellent response to therapy (nonstimulated
      Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies
      [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response
      (nonstimulated Tg for TT 0.2-5 ng/mL, stable or declining TgAb and/or nonspecific
      imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete
      response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or
      increasing Tg with similar TSH levels and/or increasing TgAb and negative
      imaging; n = 6/19) and all (100%) patients with structural incomplete response (n
      = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were
      significantly modified based on response to therapy assessment. CONCLUSIONS: Our
      data validate the newly proposed response to therapy assessment in patients with
      DTC treated with lobectomy or TT without RAI as an effective tool to modify
      initial risk estimates of recurrent/persistent SED and better tailor followup and
      future therapeutic approaches. This study provides further evidence to support a
      selective use of RAI in DTC.

PMID- 27023447
TI  - Subclinical Hypothyroidism and Thyroid Autoimmunity Are Not Associated With
      Fecundity, Pregnancy Loss, or Live Birth.
AB  - CONTEXT: Prior studies examining associations between subclinical hypothyroidism
      and antithyroid antibodies with early pregnancy loss and live birth suggest mixed
      results and time to pregnancy (TTP) has not been studied in this patient
      population. OBJECTIVE: This study sought to examine associations of prepregnancy
      TSH concentrations and thyroid autoimmunity with TTP, pregnancy loss, and live
      birth among women with proven fecundity and a history of pregnancy loss. DESIGN
      AND SETTING: This was a prospective cohort study from a large, randomized
      controlled trial that took place at four medical centers in the United States.
      PATIENTS OR OTHER PARTICIPANTS: Healthy women, ages 18-40 y, who were actively
      attempting to conceive and had one or two prior pregnancy losses and no history
      of infertility were eligible for the study. INTERVENTION: There were no
      interventions. MAIN OUTCOME MEASURE: TTP, pregnancy loss, and live birth.
      RESULTS: Women with TSH >= 2.5 mIU/L did not have an increased risk of pregnancy
      loss (risk ratio, 1.07; 95% confidence interval [CI], 0.81-1.41) or a decrease in
      live birth rate (risk ratio, 0.97; 95% CI, 0.88-1.07) or TTP (fecundability odds
      ratio, 1.09; 95% CI, 0.90-1.31) compared with women with TSH <2.5 mIU/L after
      adjustment for age and body mass index. Similar findings were observed for women
      with thyroid autoimmunity and after additional adjustment for treatment
      assignment. CONCLUSIONS: Among healthy fecund women with a history pregnancy
      loss, TSH levels >= 2.5 mIU/L or the presence of antithyroid antibodies were not
      associated with fecundity, pregnancy loss, or live birth. Thus, women with
      subclinical hypothyroidism or thyroid autoimmunity can be reassured that their
      chances of conceiving and achieving a live birth are likely unaffected by
      marginal thyroid dysfunction.

PMID- 27023448
TI  - Optimizing Blood Sampling Protocols in Patients With Acromegaly for the
      Estimation of Growth Hormone Secretion.
AB  - CONTEXT: Optimal blood sampling schemas of GH for the estimation of the 24-hour
      secretion rate have not been established in acromegalic patients. OBJECTIVE: By
      censoring available 24-hour GH serum profiles, we investigated the reliability of
      such simplified schemas. Design, Subjects, and Methods: We used 24-hour serum GH
      concentration profiles obtained with 10-minute sampling in a large cohort of
      healthy subjects (n = 130; mean age, 42; range, 18-77 years) and acromegalic
      patients (n = 87; mean age, 48; range 18-72 years). Patient categories were
      active disease, surgically cured, and somatostatin analog-treated individuals.
      The regression coefficients of determination (R(2)) and the linear slopes (beta)
      between 24-hour secretion rates or mean concentrations (144 samples) on the one
      hand and mean values with less frequent sampling on the other, decreased in
      controls and in patients a short (1-2 weeks) or long (2-5 years) time after
      successful surgery. By contrast, the regression parameters remained essentially
      unchanged in patients with active acromegaly and those under GH suppressive
      treatment. Excellent correlations (R(2) >= 0.90) without GH underestimation
      existed between mean GH of daytime profiles and mean GH of 24-hour profiles and
      GH secretion rates estimated by deconvolution in patients with active acromegaly
      and patients treated with somatostatin analogs. CONCLUSION: Simplified sampling
      schemes, particularly a day profile, can be used for the estimation of GH
      secretion in patients with active acromegaly and under medical treatment.
      However, in healthy controls and patients after successful surgery, prolonged and
      frequent sampling schemes, at least at 2-hour intervals, reliably reflect 24-hour
      secretion.

PMID- 27023449
TI  - Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory
      Biomarkers in the Multi-Ethnic Study of Atherosclerosis.
AB  - CONTEXT: Mechanisms explaining documented associations of 25-hydroxyvitamin D
      [25(OH)D] deficiency with increased risks of cardiovascular disease (CVD) and
      venous thromboembolism may relate to adverse hemostatic and inflammatory
      responses. OBJECTIVE: To evaluate whether 25(OH)D deficiency is associated with a
      prothrombotic and proinflammatory biological profile. DESIGN: Cross-sectional
      analyses. SETTING: The Multi-Ethnic Study of Atherosclerosis, a multicenter
      prospective cohort of American adults. PARTICIPANTS: Up to 6554 adults free of
      CVD. MAIN OUTCOME MEASURES: Ten hemostatic biomarkers (D-dimer, fibrinogen,
      factor VIII, plasmin-antiplasmin, and homocysteine [n = 6443]; von Willebrand
      factor, soluble tissue factor, plasminogen activator inhibitor-1 (PAI-1), total
      tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin [n = 814]),
      and three inflammatory biomarkers (IL-6, C-reactive protein [n = 6443], and TNF
      alpha soluble receptor [n = 3802]). RESULTS: Among 6443 subjects (46.6% men; mean
      age, 62.1 years; mean body mass index, 28.3 kg/m(2)) of White (37.8%), Black
      (27.2%), Chinese (12.2%), and Hispanic (21.8%) race/ethnicity, mean 25(OH)D was
      25.3 ng/mL. After multiple adjustment, 25(OH)D concentrations were associated
      with concentrations of IL-6 and homocysteine and also with concentrations of PAI
      1 and TFPI: per 10 ng/mL decrement in 25(OH)D, 5.1% higher IL-6 (95% confidence
      interval [CI], 3.4-6.9; P < .001); 3.7% higher homocysteine (95% CI, 3.0-4.3; P <
      .001); 7.0% higher PAI-1 (95% CI, 0.9-13.6; P = .025); and 2.1% higher TFPI (95%
      CI, 0.0-4.2; P = .047), without racial/ethnic heterogeneity. No significant
      associations were observed for other hemostatic and inflammatory biomarkers.
      CONCLUSIONS: Increased inflammation as reflected by higher circulating IL-6 and
      increased homocysteine concentrations may represent mechanisms linking 25(OH)D
      deficiency to greater risks of CVD and perhaps venous thromboembolism. Low
      concentrations of 25(OH)D were also associated with PAI-1 and TFPI
      concentrations, but not with other hemostatic biomarkers.

PMID- 27023450
TI  - Evaluation of Circulating Determinants of Beta-Cell Function in Women With and
      Without Gestational Diabetes.
AB  - CONTEXT: Gestational diabetes (GDM) arises in women in whom there is insufficient
      beta-cell compensation for the insulin resistance of late pregnancy. The
      mechanisms underlying both normal antepartum beta-cell adaptation and its
      aberrancy in GDM are unclear. Preclinical studies have suggested that the
      hormones prolactin and human placental lactogen (HPL) may stimulate beta-cell
      mass, whereas the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2
      furanpropanoic acid (CMPF) has recently emerged as a potential negative regulator
      of beta-cell function. However, there has been limited study of these factors in
      humans. OBJECTIVE: Our objective was to systematically evaluate HPL, prolactin,
      and CMPF in relation to glucose homeostasis and beta-cell function in women with
      and without GDM. DESIGN/SETTING/PARTICIPANTS: Three-hundred-and-ninety-five women
      underwent an oral glucose tolerance test in late pregnancy, enabling assessment
      of GDM status, glycemia (area-under-the-glucose-curve on oral glucose tolerance
      test [AUCglucose]), beta-cell function (Insulin Secretion-Sensitivity Index-2,
      insulinogenic index/homeostatic model assessment of insulin resistance [HOMA
      IR]), insulin sensitivity/resistance (Matsuda index, HOMA-IR), and circulating
      HPL, prolactin, and CMPF. RESULTS: Serum concentrations of HPL, prolactin, and
      CMPF were similar between women with GDM (n = 105) and women without GDM (n =
      290). However, on multiple linear regression analyses, CMPF emerged as a
      significant predictor of AUCglucose in women with GDM (t = 4.75, P < .0001) but
      not in their peers (P = .60). Furthermore, CMPF independently predicted lower
      Insulin Secretion-Sensitivity Index-2 (t = -2.28, P = .02) and lower
      insulinogenic index/HOMA-IR (t = -2.22, P = .03) in women with GDM but not in the
      non-GDM group (both P = .93). Neither HPL nor prolactin was significantly
      associated with AUCglucose, beta-cell function, or insulin sensitivity.
      CONCLUSION: CMPF is a potential circulating determinant of beta-cell dysfunction
      and hyperglycemia in women with GDM.

PMID- 27023451
TI  - Potential Synergies between Nature-Based Tourism and Sustainable Use of Marine
      Resources: Insights from Dive Tourism in Territorial User Rights for Fisheries in
      Chile.
AB  - Novel solutions to conserve biodiversity whilst allowing for resource harvesting
      are urgently needed. In marine systems, Territorial User Rights for Fisheries
      (TURFs) are promoted to enable sustainable use of resources. We investigate the
      potential for synergies between nature-based tourism and TURFs on Chile's central
      coast. Of 135 recreational divers surveyed, 77% indicated that the fish species
      they preferred sighting were declining and 80% indicated that they would dive
      more often in TURFs, which have higher abundance of favoured species. Regression
      analysis shows that respondents that perceive that TURFs fulfil a conservation
      function are more willing to pay to dive in a TURF. However, respondents who
      understand the bureaucratic functioning of a TURF are less willing to pay, and
      there is diversity in how divers feel payments should be made. A participatory
      approach is required to navigate these complexities to achieve synergies between
      nature-based tourism and resource harvesting in TURFs. 

PMID- 27023452
TI  - Correction: Variations in T cell transcription factor sequence and expression
      associated with resistance to the sheep nematode Teladorsagia circumcincta.

PMID- 27023453
TI  - Optical Coherence Tomography Angiography of Diabetic Retinopathy.
AB  - PURPOSE: To describe the optical coherence tomography angiography (OCTA) features
      of diabetic retinopathy. METHODS: Literature review and case series. RESULTS:
      Four cases are presented. CONCLUSION: OCTA is an effective method for evaluating
      retinal changes in diabetic retinopathy and represents a novel complement or
      alternative to fluorescein angiography. Although OCTA should currently be
      considered an investigational technique, in the near future, it may play key
      roles in the diagnosis and management of diabetic retinopathy.

PMID- 27023454
TI  - Thinking outside the box.

PMID- 27023455
TI  - An exploratory study into the impact and acceptability of formatively used
      progress testing in postgraduate obstetrics and gynaecology.
AB  - Part of recent reforms of postgraduate medical training in the Netherlands is the
      introduction of formatively intended knowledge testing or progress testing. We
      previously evaluated the construct validity and reliability of postgraduate
      progress testing. However, when assessment is intended to be formative, the
      acceptability of the test (scores) and the educational impact that is achieved
      are at least as important in the utility of this assessment format. We developed
      a questionnaire targeted at both educational supervisors and postgraduate
      trainees, containing questions on general acceptability, educational impact and
      acceptability of test content. 90 % of trainees and 84 % of educational
      supervisors completed the questionnaire. The general acceptability of formatively
      used progress testing is good; however, the self-reported educational impact is
      limited. Furthermore, trainees query the validity of test content. Formatively
      intended progress testing is well accepted; however the impact is limited. We
      discuss the importance of feedback quality and the effect of grading. Furthermore
      we start a debate on whether, for a genuine effect on learning, formative
      assessment should have consequences, either by entwining the assessment with the
      training programme or by linking the assessment to a summative standard. 

PMID- 27023456
TI  - Communicating with graduate medical trainees: the Cleveland Clinic experience.
AB  - Optimizing communication with graduate medical trainees is critical, as they
      contribute importantly to the mission of academic medical centres. Yet,
      communication is challenged by their complex schedules, geographic separation,
      and time constraints. Few studies have examined this issue to offer valuable
      solutions. Because traditional approaches are suboptimal, two communication tools
      were implemented: (1) a web-based intranet site called [graduate medical
      education] GME|com, and (2) an electronic newsletter, GME|com Headlines. The
      goals were to: (1) build a single repository of information relevant to trainees,
      programme directors, and coordinators, and (2) minimize their email burdens. A
      post-launch survey showed that >75 % of respondents indicated they visited the
      site and, of those, >90 % perceived value to the site. Analysis of use over the
      first year showed 39,377 visits (mean 108/day) and 93,785 pageviews. Sixty
      percent of users visited GME|com between 9 and 201 times and 18 % >201 times. A
      survey of programme directors from the 25 largest training programmes in the US
      confirmed the challenges of communicating with trainees and suboptimal results of
      current solutions. GME|com and Headlines represent complementary communication
      tools that have been well-received and frequently used. Future opportunities
      include assessing the association of GME|com use with increments in quality and
      patient safety. 

PMID- 27023457
TI  - Energy cost and return for hunting in African wild dogs and cheetahs.
AB  - African wild dogs (Lycaon pictus) are reported to hunt with energetically costly
      long chase distances. We used high-resolution GPS and inertial technology to
      record 1,119 high-speed chases of all members of a pack of six adult African wild
      dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly
      unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook
      even shorter, higher-speed hunts. We used an energy balance model to show that
      the energy return from group hunting and feeding substantially outweighs the cost
      of multiple short chases, which indicates that African wild dogs are more
      energetically robust than previously believed. Comparison with cheetah
      illustrates the trade-off between sheer athleticism and high individual kill rate
      characteristic of cheetahs, and the energetic robustness of frequent
      opportunistic group hunting and feeding by African wild dogs. 

PMID- 27023458
TI  - Overexpression of a synthetic insect-plant geranyl pyrophosphate synthase gene in
      Camelina sativa alters plant growth and terpene biosynthesis.
AB  - MAIN CONCLUSION: A novel plastidial homodimeric insect-plant geranyl
      pyrophosphate synthase gene is synthesized from three different cDNA origins. Its
      overexpression in Camelina sativa effectively alters plant development and
      terpenoid metabolism. Geranyl pyrophosphate synthase (GPPS) converts one
      isopentenyl pyrophosphate and dimethylallyl pyrophosphate to GPP. Here, we report
      a synthetic insect-plant GPPS gene and effects of its overexpression on plant
      growth and terpenoid metabolism of Camelina sativa. We synthesized a 1353-bp
      cDNA, namely PTP-MpGPPS. This synthetic cDNA was composed of a 1086-bp cDNA
      fragment encoding a small GPPS isomer of the aphid Myzus persicae (Mp), 240-bp
      Arabidopsis thaliana cDNA fragment encoding a plastidial transit peptide (PTP),
      and a 27-bp short cDNA fragment encoding a human influenza hemagglutinin tag
      peptide. Structural modeling showed that the deduced protein was a homodimeric
      prenyltransferase. Confocal microscopy analysis demonstrated that the PTP-MpGPPS
      fused with green florescent protein was localized in the plastids. The synthetic
      PTP-MpGPPS cDNA driven by 2 * 35S promoters was introduced into Camelina
      (Camelina sativa) by Agrobacterium-mediated transformation and its overexpression
      in transgenic plants were demonstrated by western blot. T2 and T3 progeny of
      transgenic plants developed larger leaves, grew more and longer internodes, and
      flowered earlier than wild-type plants. Metabolic analysis showed that the levels
      of beta-amyrin and campesterol were higher in tissues of transgenic plants than
      in those of wild-type plants. Fast isoprene sensor analysis demonstrated that
      transgenic Camelina plants emitted significantly less isoprene than wild-type
      plants. In addition, transcriptional analyses revealed that the expression levels
      of gibberellic acid and brassinosteroids-responsive genes were higher in
      transgenic plants than in wild-type plants. Taken together, these data
      demonstrated that this novel synthetic insect-plant GPPS cDNA was effective to
      improve growth traits and alter terpenoid metabolism of Camelina.

PMID- 27023459
TI  - How Involved are Non-VA Chaplains in Supporting Veterans?
AB  - In terms of supporting veteran populations, little is known of the experiences of
      chaplains professionally active outside of Department of Veterans Affairs (VA)
      healthcare settings. The present study looks to examine how involved non-VA
      chaplains are in supporting veterans as well as their familiarity with the VA. An
      online survey was distributed in a convenience sample of chaplains, of which n =
      39 met the inclusion criterion for this study (i.e., no past or present VA
      affiliation). The results find that most of the non-VA chaplains encounter
      veteran service users either on a weekly or monthly basis. Though familiar with
      VA services, non-VA chaplains were not sure of their veteran service users' VA
      enrollment status nor did they feel able to adequately advise their veteran
      service users on VA enrollment. The results suggest that non-VA chaplains
      actively support veteran populations. Opportunities for enhancing chaplaincy
      services and VA outreach programs are discussed. 

PMID- 27023460
TI  - Effects of the Chinese herbal formula "Zuojin Pill" on the pharmacokinetics of
      dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype.
AB  - OBJECTIVE: Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6
      isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele
      with reduced enzyme activity. In this study, we investigated the pharmacokinetic
      interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan
      in healthy Chinese volunteers with CYP2D6*10 genotype. METHODS: A
      pharmacokinetics interaction study was carried out in three groups with
      CYP2D6*1/*1 (n = 6), CYP2D6*1/*10 (n = 6), and CYP2D6*10/*10 (n = 6) genotypes.
      Each participant received a single oral dose of dextromethorphan (15 mg) followed
      by Zuojin Pill (3 g twice daily) for 7 days, and received 3 g Zuojin Pill with 15
      mg dextromethorphan in the last day. Blood samples (0-24 h) and urine samples (0
      12 h) were collected at baseline and after the administration of Zuojin Pill, and
      the samples' concentration of dextromethorphan and its main metabolite
      dextrorphan was determined. RESULTS: Compared to baseline values, co
      administration of Zuojin Pill (3 g twice daily) for 7 days increased the AUC0-24
      of dextromethorphan [mean (90 % CI)] by 3.00-fold (2.49~3.61) and 1.71-fold
      (1.42~2.06), and decreased oral clearance(CL/F) by 0.27-fold (0.2-0.40) and 0.57
      fold (0.48-0.67) in the participants with CYP2D6*1/*1 and CYP2D6*1/*10 genotypes,
      respectively. In contrast, no significant change was observed in these
      pharmacokinetic parameters of the participants with CYP2D6*10/*10 genotype.
      CONCLUSION: These data demonstrated that administration of Zuojin Pill inhibited
      moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers.
      The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10
      groups than CYP2D6 *10/*10 group.

PMID- 27023461
TI  - Medication use and drug-related problems among women at maternity wards-a cross
      sectional study from two Norwegian hospitals.
AB  - PURPOSE: There is a lack of knowledge about drug-related problems (DRPs) among
      pregnant and lactating women. The aim of this study was to determine the extent
      and type of DRPs among pregnant and lactating women in the maternity ward at two
      Norwegian hospitals. We also aimed to investigate which drugs were involved in
      the identified DRPs, and the outcome of solving the DRPs. METHODS: Patient
      reported treatment reviews were performed to assess the prevalence and type of
      DRPs among women at the two maternity wards. RESULTS: In all, 212 women were
      included in the study, of which 89 (42 %) had experienced at least one DRP (105
      DRPs in total). "Need for additional drug" (49 cases, 46.7 %) was the most
      frequent. The most frequent drug group involved in DRPs was drugs acting on the
      respiratory system, and the most common intervention was raising
      awareness/providing confidence/giving information during the patient-reported
      treatment review. CONCLUSIONS: Over four out of ten women in the maternity wards
      have DRPs, and many have questions about drug use during pregnancy and lactation.
      Many of the DRPs could probably be avoided by providing patient-reported
      treatment reviews to pregnant women as a part of antenatal care.
      Multidisciplinary collaboration including physicians, midwifes, and pharmacists
      in antenatal care and in maternity ward could possibly prevent DRPs and thereby
      promote patient safety for pregnant and lactating women.

PMID- 27023462
TI  - Longitudinal evaluation of medication underuse in older outpatients and its
      association with quality of life.
AB  - PURPOSE: We investigated the factors promoting prescribing omissions (medication
      underuse) in long-term medical care and the impact of withholding indicated
      medications on quality of life. METHODS: In a population-based cohort study of
      older ambulatory patients (ESTHER), we collected data with sequential
      questionnaires from participants and from their GPs. Concurrently, in two
      consecutive home visits, trained study physicians performed comprehensive
      geriatric assessments and recorded all medicines currently taken. Each patient's
      medication was screened for underuse using the START-2 criteria. RESULTS:
      Medication underuse (absence of >=1 indicated medication) was present in 70.3 and
      73.2 % of 989 participants at two consecutive home visit assessments,
      respectively. Following variable selection accounting for subject-specific
      heterogeneity over time, multivariate results revealed that more drugs (odds
      ratio with 95 % confidence intervals: 0.83 [0.78;0.87] per drug) and better
      cognitive status (0.93 [0.87;0.99] per point on the MMSE scale) were preventive
      factors, while worse self-reported health status (1.33 [1.05;1.67] per point on
      an 5-point scale) and increasing frequency of GP consultations (1.07 [1.00;1.15]
      per visit within the preceding 3 months) were positively associated with
      medication underuse. An increase in omitted medications over time was associated
      with worse quality of life as determined on the EuroQuol EQ-Vas and EQ-5D scales.
      CONCLUSION: In addition to general and physician-related factors, also patient
      related aspects, such as individual health appraisal, were associated with
      medication underuse. Because withholding indicated drugs was associated with
      substantially reduced quality of life, controlled intervention studies are
      necessary to confirm the notion that pharmacological appropriateness improves
      personal wellbeing.

PMID- 27023463
TI  - Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital:
      administration of interacting co-medication and QT prolongation.
AB  - PURPOSE: Some macrolide and quinolone antibiotics (MQABs) are associated with QT
      prolongation and life-threatening torsade de pointes (TdP) arrhythmia. MQAB may
      also inhibit cytochrome P450 isoenzymes and thereby cause pharmacokinetic drug
      interactions (DDIs). There is limited data on the frequency and management of
      such risks in clinical practice. We aimed to quantify co-administration of MQAB
      with interacting drugs and associated adverse drug reactions. METHODS: We
      conducted an observational study within our pharmacoepidemiological database
      derived from electronic medical records of a tertiary care hospital. Among all
      users of MQAB associated with TdP, we determined the prevalence of additional QT
      prolonging drugs and risk factors and identified contraindicated co
      administrations of simvastatin, atorvastatin, or tizanidine. Electrocardiographic
      (ECG) monitoring and associated adverse events were validated in medical records.
      RESULTS: Among 3444 administered courses of clarithromycin, erythromycin,
      azithromycin, ciprofloxacin, levofloxacin, or moxifloxacin, there were 1332 (38.7
      %) with concomitant use of additional QT-prolonging drugs. Among those, we
      identified seven cases of drug-related QT prolongation, but 49.1 % had no ECG
      monitoring. Of all MQAB users, 547 (15.9 %) had hypokalemia. Forty-four MQAB
      users had contraindicated co-administrations of simvastatin, atorvastatin, or
      tizanidine and three of those related adverse drug reactions. CONCLUSION: In the
      studied real-life setting, we found a considerable number of MQAB users with
      additional risk factors for TdP but no ECG monitoring. However, adverse drug
      reactions were rarely found, and costs vs. benefits of ECG monitoring have to be
      weighted. In contrast, avoidable risk factors and selected contraindicated
      pharmacokinetic interactions are clear targets for implementation as automated
      alerts in electronic prescribing systems.

PMID- 27023464
TI  - Evaluation of heart rate measurements in clinical studies: a prospective cohort
      study in patients with heart disease.
AB  - PURPOSE: The purpose of this study was to evaluate the measurement of heart rate
      undertaken in clinical studies by (1) assessing the repeatability and
      reproducibility of heart rate measurements by various methods and under various
      conditions and (2) determining whether a single heart rate measurement at rest is
      representative of the circadian and inter-day variation of heart rate. METHODS:
      Prospective cohort study in 102 patients with various types of heart disease at
      Duisburg Heart Center, Germany between 2011 and 2012. The heart rate measurements
      were based on self-assessment, ECG tracings at rest, and bicycle stress ECG in
      the office as well as 24-h Holter ECG. RESULTS: Office measurements and self
      assessment at rest as well as 24-h Holter ECG and self-assessment at rest are
      highly correlated, but no correlation between self-assessment and office
      recordings/24 h recordings under exercise conditions was seen. Coefficient of
      variability was below 10 % for the self-assessment and for office measurements at
      rest. There were no differences in coefficient of variability during the day and
      within the 6 days for self-assessment of heart rate at rest and circadian
      variation was normal. CONCLUSIONS: At rest heart rate measurements by various
      methods agree sufficiently and inter-day/circadian variation is adequately
      represented. Under exercise conditions self-assessment of heart rate is not
      valuable and use of 24 h Holter as well as stress ECG recordings is necessary.
      Thus, self-reported heart rate measurements by the patient at rest seem to be
      reliable, but should be used in clinical studies only for heart rate assessment
      at rest.

PMID- 27023465
TI  - Pharmacokinetics of cefoperazone/sulbactam in critically ill patients receiving
      continuous venovenous hemofiltration.
AB  - PURPOSE: Cefoperazone/sulbactam (CFP/SUL) is a beta-lactam/beta-lactamase
      inhibitor combination with little data available for the development of effective
      dosing guidelines during continuous renal replacement therapy. This study aimed
      to investigate the pharmacokinetics (PK) of cefoperazone/sulbactam in critically
      ill patients on continuous venovenous hemofiltration (CVVH). METHODS: A
      prospective, single-center, and open-label study was conducted. Critically ill
      patients receiving CVVH with 3 g cefoperazone/sulbactam (2.0/1.0 g) intravenously
      every 8 h were recruited. Serial blood and ultrafiltrate samples were paired
      collected for initial dose (occasion 1) and steady state (occasion 2). PK was
      assessed by non-compartmental analysis, and pharmacodynamics (PD) was evaluated
      by the percent of time for which drug concentrations exceed the minimum
      inhibitory concentration (%T >MIC). RESULTS: Total fourteen patients were
      enrolled. Volume of distribution at steady state (V ss) of cefoperazone and
      sulbactam for initial doses (20.8 +/- and 28.4 L, respectively) increased
      significantly compared with those in healthy volunteers (P = 0.009 for CFP, P =
      0.030 for SUL). Both cefoperazone and sulbactam showed significantly lower total
      clearance (CLt) (46.2 and 117.6 mL/min, respectively) compared with healthy
      volunteers (P = 0.000 for CFP, P = 0.017 for SUL). There is no significant
      difference in PK between occasion 1 and occasion 2 (P > 0.05). For occasion 1,
      mean CVVH clearance accounted for 34.3 and 33.9 % for CLt of cefoperazone and
      sulbactam, respectively. The minimum PD target of 60%T >MIC was achieved in seven
      of eight patients. For occasion 2, eight of nine patients achieved cefoperazone
      concentrations that were above the MIC for the entire dosing interval.
      CONCLUSIONS: PK of cefoperazone/sulbactam was altered in critically ill patients
      undergoing CVVH. Therapeutic drug monitoring would be recommended to
      individualize the dose regimen.

PMID- 27023466
TI  - No major effects of vitamin D3 (1,25 dihydroxyvitamin D3) on absorption and
      pharmacokinetics of folic acid and fexofenadine in healthy volunteers.
AB  - PURPOSE: In Caco-2 cells, folate uptake via the proton-coupled folate transporter
      (PCFT) increases significantly by a 3-day treatment with 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3). Additionally, mRNA content and protein expression of the
      transporter OATP1A2 were increased up to ninefold with 1,25(OH)2D3. We
      investigated whether these in vitro findings can be confirmed in humans in vivo.
      METHODS: Ten healthy volunteers (six women) received 5 mg folic acid orally once
      before and once together with the last intake of a 10-day course of 0.5 MUg
      1,25(OH)2D3 orally. One hundred twenty milligrams fexofenadine, an OATP1A2
      substrate, was taken in 1 day before the first folic acid intake, and again on
      the ninth day of 1,25(OH)2D3 intake. Duodenal biopsies were taken for transporter
      mRNA assessments once before and once on the ninth or tenth day of the vitamin D3
      course. Serum folic acid and fexofenadine concentrations were quantified with a
      chemiluminescence immunoassay and LC-MS/MS, respectively. Pharmacokinetics were
      compared between periods with standard bioequivalence approaches. RESULTS: While
      geometric mean folic acid AUC0-2h, which mainly reflects absorption, was 0.403
      and 0.414 mg/L.h before and after the vitamin D3 course (geometric mean ratio
      (GMR), 1.027; 90 % confidence interval (90 % CI), 0.788-1.340), the geometric
      mean fexofenadine AUC0-2h was 1.932 and 2.761 mg/L.h, respectively (GMR, 1.429;
      90 % CI, 0.890-2.294). PCFT- and OATP1A2-mRNA expressions in duodenal biopsies
      were essentially unchanged. CONCLUSIONS: No significant changes in folic acid and
      fexofenadine absorption were observed after a 10-day course of 1,25(OH)2D3 in
      humans in vivo. This study underlines the importance of confirming in vitro
      findings in vivo in humans.

PMID- 27023468
TI  - Visual acuity and magnification devices in dentistry.
AB  - This review discusses visual acuity in dentistry and the influence of optical
      aids. Studies based on objective visual tests at a dental working distance were
      included. These studies show dramatic individual variation independent of the
      dentists? age. The limitations due to presbyopia begin at an age of 40 years.
      Dental professionals should have their near vision tested regularly. Visual
      deficiencies can be compensated with magnification aids. It is important to
      differentiate between Galilean and Keplerian loupes. The lightweight Galilean
      loupes allow an almost straight posture and offer improved ergonomics. Younger
      dentists profit more from the ergonomic aspects, while dentists over the age of
      40 can compensate their age-related visual deficiencies when using this type of
      loupe. Keplerian loupes, with their superior optical construction, improve the
      visual performance for dentists of all age groups. The optical advantages come at
      the cost of ergonomic constraints due to the weight of these loupes. The
      microscope is highly superior visually and ergonomically, and it is indispensable
      for the visual control of endodontic treatments. 

PMID- 27023467
TI  - Comorbidities and concurrent medications increasing the risk of adverse drug
      reactions: prevalence in French benzodiazepine users.
AB  - PURPOSE: To estimate benzodiazepine prevalence of use and to quantify, in
      benzodiazepine users, the prevalence of comorbidities and concurrent medications
      increasing the risk of adverse drug reactions (ADRs). METHODS: Cross-sectional
      study performed using data from the French national healthcare insurance system.
      The prevalence of use was estimated by considering as users, patients who had at
      least one benzodiazepine reimbursement during the year 2013. Patients at
      increased risk for benzodiazepine ADRs were those who had (i) drug-drug
      interactions at risk for central nervous system and respiratory depression and
      (ii) comorbidities at risk for adverse respiratory effects, or for falls or
      fractures. RESULTS: Overall, the prevalence of benzodiazepine use in 2013 was
      estimated to be 13.8 %; it was higher among women and increased with age. This
      prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic
      benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at
      increased risk for benzodiazepine ADRs; this proportion increased with age. Drug
      drug interactions represented the most prevalent condition (39.3 % of
      benzodiazepine users). The drugs most frequently involved were opioids:
      analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine
      users had comorbidities at increased risk for adverse respiratory effects (13.9 %
      in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or
      fractures (13.4 % in those aged >=80). CONCLUSIONS: This study found that
      benzodiazepine use remained high in France, and that roughly half of the users
      presented with comorbidities and concurrent medications increasing the risk of
      ADRs. These findings are of concern, given that benzodiazepines are frequently
      used, and especially among the elderly.

PMID- 27023469
TI  - Vitamin D, PTH, and calcium in relation to survival following prostate cancer.
AB  - PURPOSE: Epidemiological studies suggest that low levels of vitamin D constitute
      a risk factor for prostate cancer. However, the results are conflicting, perhaps
      because prostate cancer is a very heterogeneous disease. More recent studies have
      focused on cancer progression and mortality. Vitamin D is closely related to both
      calcium metabolism and parathyroid hormone (PTH) levels, and all three factors
      have been implicated in prostate cancer. METHODS: We examined the associations
      between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and
      mortality among 943 participants within the Malmo Diet and Cancer Study, who were
      diagnosed with prostate cancer. The mean time from diagnosis until the end of
      followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of
      follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and
      the risk of death from prostate cancer was analyzed using Cox proportional hazard
      analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models
      were adjusted for season and year of inclusion, age at baseline, age at
      diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason
      score). RESULTS: We observed a trend toward a lower prostate-specific mortality
      with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically
      significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the
      first (<68 nmol/L), HR 0.54 (0.34-0.85) when adjusting for age, time of
      inclusion, and BMI. The association was further strengthened when adjusted for
      age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36
      (0.22-0.60). p for trend was 0.03. Regarding calcium, there was a significantly
      lower HR for the second quartile (2.35-2.39 mmol/L) compared to the first (<=2.34
      mmol/L) with a HR of 0.54 (0.32-0.86) in the unadjusted analysis. However, this
      association disappeared when adjusting for tumor characteristics. There were no
      associations between levels of PTH and prostate cancer mortality. CONCLUSION:
      This study shows that levels of pre-diagnostic vitamin D above 85 nmol/L may
      improve survival in men with prostate cancer.

PMID- 27023470
TI  - A prospective study of phobic anxiety, risk of ovarian cancer, and survival among
      patients.
AB  - PURPOSE: In ovarian cancer patients and mouse models, psychosocial stress is
      associated with higher circulating markers of angiogenesis and cell migration,
      impaired immune response, and increasing tumor burden and aggressiveness. In the
      Nurses' Health Studies (NHS/NHSII), we assessed whether phobic anxiety, a marker
      of chronic distress, was associated with risk of incident ovarian cancer as well
      as survival among ovarian cancer patients. METHODS: We used Cox proportional
      hazards regression to model the relative risks (RRs) and 95 % confidence
      intervals (CI) of ovarian cancer incidence and survival by categories of the
      Crown-Crisp phobic anxiety index (CCI). RESULTS: We identified 779 cases of
      ovarian cancer during 2,497,892 person-years of follow-up. For baseline CCI (NHS:
      1988; NHSII: 1993), we observed a statistically nonsignificant increased risk of
      epithelial ovarian cancer (RR for CCI >= 4 vs. 0 or 1: 1.14; 95 % CI 0.96-1.36).
      However, when we updated CCI (NHS: 2004; NHSII: 2005), the associations were
      attenuated. Pre-diagnosis CCI was not associated with ovarian cancer survival (RR
      for >=4 vs. 0 or 1: 1.00; 95 % CI 0.77-1.31); results were similar for post
      diagnosis CCI. CONCLUSIONS: Distress, as measured by phobic anxiety symptoms, was
      not associated with ovarian cancer risk, although we cannot rule out a modest
      association. Future research should explore the role of phobic anxiety and other
      forms of psychological distress and ovarian cancer risk and survival.

PMID- 27023471
TI  - Utilizing Combined Methodologies to Define the Role of Plasma Membrane Delivery
      During Axon Branching and Neuronal Morphogenesis.
AB  - During neural development, growing axons extend to multiple synaptic partners by
      elaborating axonal branches. Axon branching is promoted by extracellular guidance
      cues like netrin-1 and results in dramatic increases to the surface area of the
      axonal plasma membrane. Netrin-1-dependent axon branching likely involves
      temporal and spatial control of plasma membrane expansion, the components of
      which are supplied through exocytic vesicle fusion. These fusion events are
      preceded by formation of SNARE complexes, comprising a v-SNARE, such as VAMP2
      (vesicle-associated membrane protein 2), and plasma membrane t-SNAREs, syntaxin-1
      and SNAP25 (synaptosomal-associated protein 25). Detailed herein isa multi
      pronged approach used to examine the role of SNARE mediated exocytosis in axon
      branching. The strength of the combined approach is data acquisition at a range
      of spatial and temporal resolutions, spanning from the dynamics of single vesicle
      fusion events in individual neurons to SNARE complex formation and axon branching
      in populations of cultured neurons. This protocol takes advantage of established
      biochemical approaches to assay levels of endogenous SNARE complexes and Total
      Internal Reflection Fluorescence (TIRF) microscopy of cortical neurons expressing
      VAMP2 tagged with a pH-sensitive GFP (VAMP2-pHlourin) to identify netrin-1
      dependent changes in exocytic activity in individual neurons. To elucidate the
      timing of netrin-1-dependent branching, time-lapse differential interference
      contrast (DIC) microscopy of single neurons over the order of hours is utilized.
      Fixed cell immunofluorescence paired with botulinum neurotoxins that cleave SNARE
      machinery and block exocytosis demonstrates that netrin-1 dependent axon
      branching requires SNARE-mediated exocytic activity. 

PMID- 27023472
TI  - A Single Nucleotide Polymorphism (rs1056629) in 3'-UTR of MMP-9 is Responsible
      for a Decreased Risk of Metastatic Osteosarcoma by Compromising its Interaction
      with microRNA-491-5p.
AB  - BACKGROUND: This study aimed to explore the roles of microRNA-491-5p (miR-491)
      and its target MMP9 in the control of metastasis of osteosarcoma (OS) as well as
      how the rs1056629 polymorphism in the 3' untranslated region (3'UTR) of MMP9
      compromises the interaction between miR-491 and MMP9. METHODS: We used
      bioinformatics tools to identify possible binding sites of miR-491 in the 3'UTR
      of MMP9 and 30 OS tissue samples were collected and divided into two groups based
      on the rs1056629 genotype (AA, N=20; AC, N=8; and CC N=2). The expression of miR
      491 and MMP9 were determined in those samples. RESULTS: We found that the
      rs1056629 polymorphism potentially compromised the interaction between miRNA and
      mRNA, which was subsequently confirmed by using the luciferase reporter system.
      we found that the expression of miR-491 was comparable among the genotype groups,
      whereas the expression of MMP9 was much higher in the AC/CC groups than in the AA
      group. Furthermore, 10 OS cell lines (OSA, MG-63, Saos-2, U2OS, SARG, KPD, OHS,
      HAL, ZK-58, and MHM) were genotyped for the rs1056629 polymorphism, and MG-63
      (AA) and OSA (AC) were identified for the scratch test and Transwell assay that
      followed. In the MG-63 cells, transfection of the miR-491 mimics and MMP9 siRNA
      similarly and substantially down regulated the expression of MMP9, and miRNA and
      siRNA clearly suppressed the migratory and invasive ability. In the OSA cells,
      only MMP9 siRNA notably reduced the expression of MMP9 and decreased the
      migratory and invasive ability. The introduction of miR-491 mimics left the
      expression of MMP9 and the migratory and invasive ability intact. CONCLUSION: We
      found that the rs1056629 polymorphism interfered with the interaction between
      MMP9 mRNA and miR-491 and is associated with the metastasis of OS cells.

PMID- 27023473
TI  - Optical Coherence Tomography Angiography in Healthy Subjects.
AB  - Fluorescein angiography and indocyanine green angiography provide information
      about normal retinal and choroidal anatomy that is nearly comparable to
      histological findings. These results are absolutely fundamental for the
      evaluation of retinal and choroidal vascular diseases and allow the clinician to
      define and diagnose several pathological conditions. Fluorescein angiography has
      become the 'gold standard' in retinal imaging due to its capacity to allow
      visualization of the retinal capillary bed and its changes, particularly in the
      macular area. Although the fluorescence of the injected dye enables improved
      visualization of retinal capillaries, not all of the different layers of the
      retinal capillary network can be visualized using this bi-dimensional examination
      technique, possibly because of a light scattering phenomenon. Optical coherence
      tomography angiography allows depth-resolved visualization of the retinal and
      choroidal microvasculature by calculating the difference between static and
      nonstatic tissue. Given that the main moving elements in the eye fundus are
      contained within vessels, determining a vascular decorrelation signal enables
      three-dimensional visualization of the retinal and choroidal vascular network
      without the administration of intravenous dye and therefore reduces the risk of
      potential adverse events. 

PMID- 27023474
TI  - Overcoming the Limiting Step of Fe2O3 Reduction via in Situ Sulfide Modification.
AB  - Iron-based alkaline batteries are extremely attractive due to iron's
      environmental friendliness, and low cost. The parasitic reaction of H2 evolution
      and the poor electrical conductivity of the discharge products are among the
      major barriers for the commercialization of these batteries. In this paper, we
      first show that O(2-) diffusion inside the solid Fe2O3 particles is the rate
      limiting step in the reduction reaction. In situ sulfide modified Fe2O3, which
      has a core-shell structure verified by SEM, XRD and XPS analysis, has excellent
      electrical and ionic conductivity. The functional mechanism of sulfide in the
      reaction was identified as in the potential region around -1.071 V (vs Hg/HgO),
      the outside layer of Fe2O3 was reduced to amorphous FeS, which has good
      electrical conductivity and enlarges the electrochemical reaction interface. O(2
      ) diffusion inside the Fe2O3 particle is still the rate-limiting step. In the
      potential region around -1.15 V (vs Hg/HgO), amorphous FeS ages to FeS
      (pyrrhotite), FeS2 (marcasite), and FeS0.9 (mackinawite), which have high
      electrical conductivity. FeS0.9 can also introduce vacancies into Fe2O3
      particles, which can greatly enhance O(2-) diffusion and the ionic conductivity,
      and the surface reaction is the rate-limiting step. In summary, after in situ
      sulfide modification, the ohmic overpotential and ion diffusion overpotential for
      Fe2O3 reduction were significantly reduced. The reduction reaction rate increases
      26 times and the discharge capacity of Fe2O3 electrode increases 78 times after
      sulfide modification.

PMID- 27023476
TI  - Effect of endourological procedures on erectile function: a prospective cohort
      study.
AB  - INTRODUCTION: Many patients offered endourological procedures are concerned about
      potential sexual dysfunction following endoscopy, and there are scarce published
      data to support an evidence-based response. We aim to assess possible effects of
      endourological procedures on sexual activity and erectile function. PATIENTS AND
      METHODS: Sexually active men undergoing cystoscopy and/or upper tract
      endourological procedures were enrolled and evaluated using the IIEF-5 score and
      the IPSS, filled the day before and 10 days and 45-60 days after the procedure.
      Patients' characteristics (age, chronic medical condition, smoking, and
      medications) were recorded. The primary outcome was the change in the IIEF-5
      score. RESULTS: One hundred patients aged 24-60 years (mean 37.4) underwent
      endourological procedures (42 PCNLs, 30 ureteroscopies, 22 retrograde
      ureteropyelographies +/- stenting, and 6 cystolitholapaxies) between January and
      August 2014. Preoperative IPSS ranged from 0 to 32 (mean [SD] 11.93 [8.64]),
      while IIEF-5 ranged from 14 to 25 (mean [SD] 21.63 [2.96]), with eight patients
      in the mild to moderate (12-16) ED range, 31 mild ED (17-21), and 59 no ED (22
      25). Following the procedure, the IPSS improved (mean IPSS down from 11.9 to 6.1
      at 10 days and 6.2 at 45 days, P < 0.001), while the IIEF remained unchanged
      [21.6 preoperative to 21.0 at 10 days (P = 0.43) and 21.7 at 45 days (P = 0.81)].
      Patients with indwelling ureteric stents (28 patients) had significant LUTS
      postoperatively with a mean [SD] IPSS of 9.8 [7.2] at 10 days and 11.6 [7.8] at
      45 days. The IIEF-5 score was not affected with a mean [SD] of 21.5 [3.3] at 10
      days and 21.8 [3.1] at 45 days, compared to 22.0 [3.0] preoperatively (P = 0.44).
      CONCLUSION: Endoscopic procedures did not negatively impact erectile function and
      sexual activity.

PMID- 27023475
TI  - Storage Temperature Alters the Expression of Differentiation-Related Genes in
      Cultured Oral Keratinocytes.
AB  - PURPOSE: Storage of cultured human oral keratinocytes (HOK) allows for
      transportation of cultured transplants to eye clinics worldwide. In a previous
      study, one-week storage of cultured HOK was found to be superior with regard to
      viability and morphology at 12 degrees C compared to 4 degrees C and 37 degrees
      C. To understand more of how storage temperature affects cell phenotype, gene
      expression of HOK before and after storage at 4 degrees C, 12 degrees C, and 37
      degrees C was assessed. MATERIALS AND METHODS: Cultured HOK were stored in HEPES-
      and sodium bicarbonate-buffered Minimum Essential Medium at 4 degrees C, 12
      degrees C, and 37 degrees C for one week. Total RNA was isolated and the gene
      expression profile was determined using DNA microarrays and analyzed with Partek
      Genomics Suite software and Ingenuity Pathway Analysis. Differentially expressed
      genes (fold change > 1.5 and P < 0.05) were identified by one-way ANOVA. Key
      genes were validated using qPCR. RESULTS: Gene expression of cultures stored at 4
      degrees C and 12 degrees C clustered close to the unstored control cultures.
      Cultures stored at 37 degrees C displayed substantial change in gene expression
      compared to the other groups. In comparison with 12 degrees C, 2,981 genes were
      differentially expressed at 37 degrees C. In contrast, only 67 genes were
      differentially expressed between the unstored control and the cells stored at 12
      degrees C. The 12 degrees C and 37 degrees C culture groups differed most
      significantly with regard to the expression of differentiation markers. The
      Hedgehog signaling pathway was significantly downregulated at 37 degrees C
      compared to 12 degrees C. CONCLUSION: HOK cultures stored at 37 degrees C showed
      considerably larger changes in gene expression compared to unstored cells than
      cultured HOK stored at 4 degrees C and 12 degrees C. The changes observed at 37
      degrees C consisted of differentiation of the cells towards a squamous epithelium
      specific phenotype. Storing cultured ocular surface transplants at 37 degrees C
      is therefore not recommended. This is particularly interesting as 37 degrees C is
      the standard incubation temperature used for cell culture.

PMID- 27023477
TI  - Rs10887800 renalase gene polymorphism is associated with an increased risk of
      coronary artery disease in hemodialyzed patients.
AB  - PURPOSE: Coronary artery disease (CAD) is common in patients with end-stage renal
      disease (ESRD). Recent studies have suggested that renalase, a novel FAD
      dependent amine oxidase, may play an important role in the pathogenesis of
      cardiovascular complications in ESRD patients. The aim of the study was to
      investigate the association between renalase gene polymorphisms and a risk of CAD
      in patients on hemodialysis. METHODS: In a case-control study, a total of 309
      hemodialyzed patients (107 with and 202 without CAD) were genotyped for two SNPs
      in the renalase gene (rs10887800 and rs2576178) using the PCR-RFLP method.
      RESULTS: By multivariate logistic regression analysis, we found that rs10887800GG
      genotype was associated with an increased risk of CAD under the codominant model
      [GG vs AA; adjusted OR 2.66 (95 % CI, 1.19-5.94), p = .017] and under the
      recessive model [GG vs AG + AA; adjusted OR 2.10 (95 % CI, 1.10-4.02), p = .025].
      The rs2576178 polymorphism did not influence the risk of CAD. CONCLUSION: The
      study suggested for the first time that the rs10887800 renalase gene polymorphism
      may be involved in the pathogenesis of CAD in hemodialyzed patients and thus
      could be considered a new genetic risk factor for CAD in this population.

PMID- 27023479
TI  - The Trimethylamine-Formic Acid Complex: Microwave Characterization of a Prototype
      for Potential Precursors to Atmospheric Aerosol.
AB  - The reactions of amines and carboxylic acids have recently received attention for
      their possible role in the formation of atmospheric aerosol. Here, we report a
      microwave study of the trimethylamine-formic acid hydrogen-bonded complex, a
      simple prototype in which to study amine-carboxylic acid interactions. Spectra of
      three isotopologues of the system have been observed using a tandem cavity and
      chirped-pulse Fourier transform microwave spectrometer. The complex has a plane
      of symmetry, with the acidic proton of the formic acid directed toward the lone
      pair of the nitrogen. The zero-point-averaged hydrogen bond length is 1.702 A,
      and the O-H...N angle is 177 degrees . (14)N nuclear quadrupole hyperfine
      structure has been used to assess the degree of proton transfer from the formic
      acid to the trimethylamine. Experimental results are supplemented with density
      functional theory calculations. M06-2X/6-311++G(3df,3pd) calculations indicate a
      binding energy of 16.8 kcal/mol with counterpoise correction (17.4 kcal/mol
      without counterpoise correction). 

PMID- 27023478
TI  - Soluble intracellular adhesion molecule-1 and omentin-1 as potential biomarkers
      of subclinical atherosclerosis in hemodialysis patients.
AB  - PURPOSE: Atherosclerotic cardiovascular complications represent significant cause
      of mortality in hemodialysis (HD) patients. The aims of this study were to: (a)
      investigate association of sICAM-1, sVCAM-1, omentin-1 and other non-traditional
      risk factors with subclinical atherosclerosis; (b) examine the diagnostic value
      of these specific markers in the early detection of subclinical atherosclerosis;
      and (c) examine their role as predictors of mortality in group of patients with
      subclinical atherosclerosis on regular HD. MATERIALS AND METHODS: Starting from
      November 2011, a cohort of 210 HD patients participated in this 3-year follow-up
      study. The subjects were divided into three groups according to the presence of
      atherosclerosis. Atherosclerotic disease was assessed by measuring carotid intima
      media thickness (IMT). Samplings were withdrawn at baseline and thereafter every
      12 months until the end of follow-up. RESULTS: IMT showed weak correlation with
      sICAM-1 (r = 0.39, P = 0.001), sVCAM-1 (r = 0.27, P = 0.015) and omentin-1 (r = 
      0.25, P = 0.020), and also omentin-1 showed good correlation with parameters of
      systolic and diastolic function (r = 0.52, P = 0.001 and r = 0.51, P = 0.001).
      Multivariate analysis showed that sICAM-1 and sVCAM-1 concentrations were a
      strong independent correlate of IMT (P = 0.031 and P = 0.010, respectively). The
      Cox proportional analysis showed that sICAM-1 and omentin-1 concentrations were
      strong predictors of cardiovascular death (HR 1.85, CI 1.18-2.32, P = 0.021 and
      HR 4.14, CI 1.38-12.1, P = 0.004, respectively) and that serial measurements of
      these markers predict IMT progression (HR 1.98, 95 % CI 1.21-2.38, P < 0.002 and
      HR 2.91, 95 % CI 1.57-4.72, P < 0.001, respectively). CONCLUSIONS: Our study
      demonstrated that sICAM-1 and omentin-1 levels are strong predictors of
      cardiovascular death in HD patients with subclinical atherosclerosis.

PMID- 27023481
TI  - [Not Available].

PMID- 27023482
TI  - [Journal Sportverletzung Sportschaden--Quo vadis 2016?].

PMID- 27023483
TI  - A Whole Mount In Situ Hybridization Method for the Gastropod Mollusc Lymnaea
      stagnalis.
AB  - Whole mount in situ hybridization (WMISH) is a technique that allows for the
      spatial resolution of nucleic acid molecules (often mRNAs) within a 'whole mount'
      tissue preparation, or developmental stage (such as an embryo or larva) of
      interest. WMISH is extremely powerful because it can significantly contribute to
      the functional characterization of complex metazoan genomes, a challenge that is
      becoming more of a bottleneck with the deluge of next generation sequence data.
      Despite the conceptual simplicity of the technique much time is often needed to
      optimize the various parameters inherent to WMISH experiments for novel model
      systems; subtle differences in the cellular and biochemical properties between
      tissue types and developmental stages mean that a single WMISH method may not be
      appropriate for all situations. We have developed a set of WMISH methods for the
      re-emerging gastropod model Lymnaea stagnalis that generate consistent and clear
      WMISH signals for a range of genes, and across all developmental stages. These
      methods include the assignment of larvae of unknown chronological age to an
      ontogenetic window, the efficient removal of embryos and larvae from their egg
      capsules, the application of an appropriate Proteinase-K treatment for each
      ontogenetic window, and hybridization, post-hybridization and immunodetection
      steps. These methods provide a foundation from which the resulting signal for a
      given RNA transcript can be further refined with probe specific adjustments
      (primarily probe concentration and hybridization temperature). 

PMID- 27023484
TI  - Water in Oil Emulsions: A New System for Assembling Water-soluble Chlorophyll
      binding Proteins with Hydrophobic Pigments.
AB  - Chlorophylls (Chls) and bacteriochlorophylls (BChls) are the primary cofactors
      that carry out photosynthetic light harvesting and electron transport. Their
      functionality critically depends on their specific organization within large and
      elaborate multisubunit transmembrane protein complexes. In order to understand at
      the molecular level how these complexes facilitate solar energy conversion, it is
      essential to understand protein-pigment, and pigment-pigment interactions, and
      their effect on excited dynamics. One way of gaining such understanding is by
      constructing and studying complexes of Chls with simple water-soluble recombinant
      proteins. However, incorporating the lipophilic Chls and BChls into water-soluble
      proteins is difficult. Moreover, there is no general method, which could be used
      for assembly of water-soluble proteins with hydrophobic pigments. Here, we
      demonstrate a simple and high throughput system based on water-in-oil emulsions,
      which enables assembly of water-soluble proteins with hydrophobic Chls. The new
      method was validated by assembling recombinant versions of the water-soluble
      chlorophyll binding protein of Brassicaceae plants (WSCP) with Chl a. We
      demonstrate the successful assembly of Chl a using crude lysates of WSCP
      expressing E. coli cell, which may be used for developing a genetic screen system
      for novel water-soluble Chl-binding proteins, and for studies of Chl-protein
      interactions and assembly processes. 

PMID- 27023485
TI  - Vibronic Effects on Rates of Excitation Energy Transfer and Their Temperature
      Dependence.
AB  - Vibronic effects on rate constants governing excitation energy transfer between
      different electronic states have been studied within the adiabatic regime and the
      harmonic oscillator approximation, possibly including bulk solvent effects with
      the polarizable continuum model. A recent implementation in the Gaussian package
      has been extended for this purpose, with the possibility of taking into account
      frequency shifts and mode mixing effects between ground and excited electronic
      states. The potentialities of the new computational tool have been analyzed for a
      number of case studies, including excimers of naphthalene and zinc porphyrin
      complexes. In all cases, the change of rate constants with temperature arising
      from the inclusion of vibronic effects is in good qualitative agreement with the
      available experimental data. 

PMID- 27023486
TI  - Effects of slip severity on muscle activation of the trailing leg during an
      unexpected slip.
AB  - Falls and injuries due to falls are a major health concern, and accidental slips
      are a leading cause of falls during gait. Understanding how the body reacts to an
      unexpected slip can aid in developing intervention techniques to reduce the
      number of injuries due to falls. In this study, muscle activation patterns,
      specifically those of the trailing (non-slipping) limb, were studied in
      unexpected slips of 24 young and 24 middle-aged adults. The typical reaction of
      the trailing limb is swing phase interruption in an attempt to arrest the slip.
      Variables examined were the reactive muscle activation onset, peak
      electromyography (EMG) magnitude, and time-to-peak of the vastus lateralis and
      medial hamstring of the trailing limb. Statistical analysis was performed to
      determine the effects of slip severity, quantified by peak slip velocity, and age
      on outcome variables. As slip severity increased, the reactive activation onset
      of the medial hamstring was significantly faster and there was a trend
      approaching significance for the onset of the vastus lateralis. Additionally, the
      peak magnitude and time-to-peak of the vastus lateralis increased with slip
      severity. No significant effects of age were found on any of the output
      variables. These findings may aid in development of perturbation-based paradigms,
      as it may be possible to "tune" the postural control system to generate an
      appropriate response to unexpected slips. 

PMID- 27023487
TI  - Antipsychotic-related fatal poisoning, England and Wales, 1993-2013: impact of
      the withdrawal of thioridazine.
AB  - CONTEXT: Use of second generation antipsychotics in England and Wales has
      increased in recent years whilst prescription of first generation antipsychotics
      has decreased. METHODS: To evaluate the impact of this change and of the
      withdrawal of thioridazine in 2000 on antipsychotic-related fatal poisoning, we
      reviewed all such deaths in England and Wales 1993-2013 recorded on the Office
      for National Statistics drug poisoning deaths database. We also reviewed
      antipsychotic prescribing in the community, England and Wales, 2001-2013. Use of
      routine mortality data: When an antipsychotic was recorded with other drug(s),
      the death certificate does not normally say if the antipsychotic caused the death
      rather than the other substance(s). A second consideration concerns intent. A
      record of "undetermined intent" is likely to have been intentional self
      poisoning, the evidence being insufficient to be certain that the individual
      intended to kill. A record of drug abuse/dependence, on the other hand, is likely
      to have been associated with an unintentional death. Accuracy of the diagnosis of
      poisoning: When investigating a death in someone prescribed antipsychotics,
      toxicological analysis of biological samples collected post-mortem is usually
      performed. However, prolonged attempts at resuscitation, or diffusion from
      tissues into blood as autolysis proceeds, may serve to alter the composition of
      blood sampled after death from that circulating at death. With chlorpromazine and
      with olanzapine a further factor is that these compounds are notoriously unstable
      in post-mortem blood. Deaths from antipsychotics: There were 1544 antipsychotic
      related poisoning deaths. Deaths in males (N = 948) were almost twice those in
      females. For most antipsychotics, the proportion of deaths in which a specific
      antipsychotic featured either alone, or only with alcohol was 30-40%, but for
      clozapine (193 deaths) such mentions totalled 66%. For clozapine, the proportion
      of deaths attributed to either intentional self-harm, or undetermined intent was
      44%, but for all other drugs except haloperidol (20 deaths) the proportion was
      56% or more. The annual number of antipsychotic-related deaths increased from
      some 55 per year (1.0 per million population) between 1993 and 1998 to 74 (1.5
      per million population) in 2000, and then after falling slightly in 2002
      increased steadily to reach 109 (1.9 per million population) in 2013. Intent: The
      annual number of intentional and unascertained intent poisoning deaths remained
      relatively constant throughout the study period (1993: 35 deaths, 2013: 38
      deaths) hence the increase in antipsychotic-related deaths since 2002 was almost
      entirely in unintentional poisoning involving second generation antipsychotics.
      Clozapine, olanzapine, and quetiapine were the second generation antipsychotics
      mentioned most frequently in unintentional poisonings (99, 136, and 99 deaths,
      respectively). Mentions of diamorphine/morphine and methadone (67 and 99 deaths,
      respectively) together with an antipsychotic were mainly (84 and 90%,
      respectively) in either unintentional or drug abuse-related deaths. Deaths and
      community prescriptions: Deaths involving antipsychotics (10 or more deaths) were
      in the range 11.3-17.1 deaths per million community prescriptions in England and
      Wales, 2001-2013. Almost all (96%) such deaths now involve second generation
      antipsychotics. This is keeping with the increase in annual numbers of
      prescriptions of these drugs overall (<1 million in 2000, 7 million in 2013),
      largely driven by increases in prescriptions for olanzapine and quetiapine. In
      contrast, deaths involving thioridazine declined markedly (from 40 in 2000 to 10
      in 2003-2013) in line with the fall in prescriptions for thioridazine from 2001.
      CONCLUSIONS: The removal of thioridazine has had no apparent effect on the
      incidence of antipsychotic-related fatal poisoning in England and Wales. That
      such deaths have increased steadily since 2001 is in large part attributable to
      an increase in unintentional deaths related to (i) clozapine, and (ii) co
      exposure to opioids, principally diamorphine and methadone.

PMID- 27023488
TI  - A Duplex Digital PCR Assay for Simultaneous Quantification of the Enterococcus
      spp. and the Human Fecal-associated HF183 Marker in Waters.
AB  - This manuscript describes a duplex digital PCR assay (EntHF183 dPCR) for
      simultaneous quantification of Enterococcus spp. and the human fecal-associated
      HF183 marker. The EntHF183 duplex dPCR (referred as EntHF183 dPCR hereon) assay
      uses the same primer and probe sequences as its published individual quantitative
      PCR (qPCR) counterparts. Likewise, the same water filtration and DNA extraction
      procedures as performed prior to qPCR are followed prior to running dPCR.
      However, the duplex dPCR assay has several advantages over the qPCR assays. Most
      important, the dPCR assay eliminates the need for running a standard curve and
      hence, the associated bias and variability, by direct quantification of its
      targets. In addition, while duplexing (i.e., simultaneous quantification)
      Enterococcus and HF183 in qPCR often leads to severe underestimation of the less
      abundant target in a sample, dPCR provides consistent quantification of both
      targets, whether quantified individually or simultaneously in the same reaction.
      The dPCR assay is also able to tolerate PCR inhibitor concentrations that are one
      to two orders of magnitude higher than those tolerated by qPCR. These advantages
      make the EntHF183 dPCR assay particularly attractive because it simultaneously
      provides accurate and repeatable information on both general and human-associated
      fecal contamination in environmental waters without the need to run two separate
      qPCR assays. Despite its advantages over qPCR, the upper quantification limit of
      the dPCR assay with currently available instrumentation is approximately four
      orders of magnitude lower than that achievable by qPCR. Consequently, dilution is
      needed for measurement of high concentrations of target organisms such as those
      typically observed following sewage spills.

PMID- 27023492
TI  - Examining pitch and numerical magnitude processing in congenital amusia: A quasi
      experimental pilot study.
AB  - INTRODUCTION: Congenital amusia is a developmental disorder associated with
      deficits in pitch height discrimination or in integrating pitch sequences into
      melodies. This quasi-experimental pilot study investigated whether there is an
      association between pitch and numerical processing deficits in congenital amusia.
      Since pitch height discrimination is considered a form of magnitude processing,
      we investigated whether individuals with amusia present an impairment in
      numerical magnitude processing, which would reflect damage to a generalized
      magnitude system. Alternatively, we investigated whether the numerical processing
      deficit would reflect a disconnection between nonsymbolic and symbolic number
      representations. METHOD: This study was conducted with 11 adult individuals with
      congenital amusia and a control comparison group of 6 typically developing
      individuals. Participants performed nonsymbolic and symbolic magnitude
      comparisons and number line tasks. Results were available from previous testing
      using the Montreal Battery of Evaluation of Amusia (MBEA) and a pitch change
      detection task (PCD). RESULTS: Compared to the controls, individuals with amusia
      exhibited no significant differences in their performance on both the number line
      and the nonsymbolic magnitude tasks. Nevertheless, they showed significantly
      worse performance on the symbolic magnitude task. Moreover, individuals with
      congenital amusia, who presented worse performance in the Meter subtest, also
      presented less precise nonsymbolic numerical representation. CONCLUSIONS: The
      relationship between meter and nonsymbolic numerical discrimination could
      indicate a general ratio processing deficit. The finding of preserved nonsymbolic
      numerical magnitude discrimination and mental number line representations, with
      impaired symbolic number processing, in individuals with congenital amusia
      indicates that (a) pitch height and numerical magnitude processing may not share
      common neural representations, and (b) in addition to pitch processing,
      individuals with amusia may present a deficit in accessing nonsymbolic numerical
      representations from symbolic representations. The symbolic access deficit could
      reflect a widespread impairment in the establishment of cortico-cortical
      connections between association areas.

PMID- 27023493
TI  - The genomic characteristics and cellular origin of chromothripsis.
AB  - Human genomes are continuously subjected to mutations, which can drive genetic
      diseases and cancer. An intriguing recent finding has been the discovery of
      chromothripsis, a spectacular and complex form of chromosome rearrangement that
      can occur in the genomes of cancer cells and patients with congenital diseases.
      Chromothripsis has been described in a large array of human cancers and various
      types of chromothripsis have appeared, which differ in complexity and genomic
      hallmarks. From the combined genomic data a consensus hypothesis has been
      inferred, involving aberrant DNA replication and chromosome shattering as the
      underlying processes explaining chromothripsis. In addition, recent work has
      established several cellular models that recapitulate chromothripsis under
      defined experimental conditions. One of these models indicates that
      chromothripsis can originate from DNA damage in micronuclei, providing an elegant
      explanation for the restriction of chromothriptic rearrangements to a single
      chromosome. Alternatively, chromothripsis can be caused by telomere crisis, a
      process that involves formation of dicentric chromosomes and chromatin bridges.
      Here, we summarize the genomic features of chromothripsis and we discuss
      experimental approaches that allow dissection of the chromothripsis process.

PMID- 27023495
TI  - Structure-Based Drug Design of Small Molecule Peptide Deformylase Inhibitors to
      Treat Cancer.
AB  - Human peptide deformylase (HsPDF) is an important target for anticancer drug
      discovery. In view of the limited HsPDF, inhibitors were reported, and high
      throughput virtual screening (HTVS) studies based on HsPDF for developing new PDF
      inhibitors remain to be reported. We reported here on diverse small molecule
      inhibitors with excellent anticancer activities designed based on HTVS and
      molecular docking studies using the crystal structure of HsPDF. The compound
      M7594_0037 exhibited potent anticancer activities against HeLa, A549 and MCF-7
      cell lines with IC50s of 35.26, 29.63 and 24.63 MUM, respectively. Molecular
      docking studies suggested that M7594_0037 and its three derivatives could
      interact with HsPDF by several conserved hydrogen bonds. Moreover, the
      pharmacokinetic and toxicity properties of M7594_0037 and its derivatives were
      predicted using the OSIRIS property explorer. Thus, M7594_0037 and its
      derivatives might represent a promising scaffold for the further development of
      novel anticancer drugs. 

PMID- 27023494
TI  - Lamin in inflammation and aging.
AB  - Aging is characterized by a progressive loss of tissue function and an increased
      susceptibility to injury and disease. Many age-associated pathologies manifest an
      inflammatory component, and this has led to the speculation that aging is at
      least in part caused by some form of inflammation. However, whether or not
      inflammation is truly a cause of aging, or is a consequence of the aging process
      is unknown. Recent work using Drosophila has uncovered a mechanism where the
      progressive loss of lamin-B in the fat body upon aging triggers systemic
      inflammation. This inflammatory response perturbs the local immune response of
      the neighboring gut tissue and leads to hyperplasia. Here, we will discuss the
      literature connecting lamins to aging and inflammation.

PMID- 27023496
TI  - Extraction Optimization, Purification and Physicochemical Properties of
      Polysaccharides from Gynura medica.
AB  - Extraction of polysaccharides from Gynura medica (GMPs) was optimized by response
      surface methodology (RSM). A central composition design including three
      parameters, namely extraction temperature (X1), ratio of water to raw material
      (X2) and extraction time (X3), was used. The best conditions were extraction
      temperature of 91.7  degrees C, extraction time of 4.06 h and ratio of water to
      raw material of 29.1 mL/g. Under the optimized conditions, the yield of GMPs was
      5.56%, which was similar to the predicted polysaccharides yield of 5.66%. A
      fraction named GMP-1 was obtained after isolation and purification by DEAE-52 and
      Sephadex G-100 gel chromatography, respectively. GMP-1, with a molecular weight
      of 401 kDa, mainly consisted of galacturonic acid (GalA), xylose (Xyl), glucose
      (Glu). Infrared spectroscopy was used to characterize the major functional groups
      of GMP-1 and the results indicated that it was an acidic polysaccharide. The
      antioxidant and alpha-glucosidase inhibitory activities of GMPs and GMP-1 were
      determined in vitro. The results indicated that GMPs and GMP-1 show potential for
      use in functional foods or medicines.

PMID- 27023497
TI  - Polyphenolic Profile and Targeted Bioactivity of Methanolic Extracts from
      Mediterranean Ethnomedicinal Plants on Human Cancer Cell Lines.
AB  - The methanol extracts of the aerial part of four ethnomedicinal plants of
      Mediterranean region, two non-seed vascular plants, Equisetum hyemale L. and
      Phyllitis scolopendrium (L.) Newman, and two Spermatophyta, Juniperus communis L.
      (J. communis) and Cotinus coggygria Scop. (C. coggygria), were screened against
      four human cells lines (A549, MCF7, TK6 and U937). Only the extracts of J.
      communis and C. coggygria showed marked cytotoxic effects, affecting both cell
      morphology and growth. A dose-dependent effect of these two extracts was also
      observed on the cell cycle distribution. Incubation of all the cell lines in a
      medium containing J. communis extract determined a remarkable accumulation of
      cells in the G2/M phase, whereas the C. coggygria extract induced a significant
      increase in the percentage of G1 cells. The novelty of our findings stands on the
      observation that the two extracts, consistently, elicited coherent effects on the
      cell cycle in four cell lines, independently from their phenotype, as two of them
      have epithelial origin and grow adherent and two are lymphoblastoid and grow in
      suspension. Even the expression profiles of several proteins regulating cell
      cycle progression and cell death were affected by both extracts. LC-MS
      investigation of methanol extract of C. coggygria led to the identification of
      twelve flavonoids (compounds 1-11, 19) and eight polyphenols derivatives (12-18,
      20), while in J. communis extract, eight flavonoids (21-28), a alpha-ionone
      glycoside (29) and a lignin (30) were found. Although many of these compounds
      have interesting individual biological activities, their natural blends seem to
      exert specific effects on the proliferation of cell lines either growing adherent
      or in suspension, suggesting potential use in fighting cancer. 

PMID- 27023498
TI  - A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design,
      Synthesis, and in Vitro and in Vivo Biological Evaluation.
AB  - A series of oleanolic acid derivatives were synthesized by diverse reactions,
      including the introduction of conjugated alkadiene and epoxy ring moieties formed
      by means of photosensitized oxidation. Eosin Y was used as photosensitizer during
      this process. Next the cytotoxicity of the products was evaluated on HepG2.2.15
      cells to determine the appropriate treatment concentration for the subsequent
      experiments. Most of the OA derivatives exhibited anti-HBV antigens secretion
      activity in HepG2.2.15 cells. Among the tested compounds, OA-4 (3.13 ug/mL)
      showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA
      replication with inhibitory ratios of 90.52% +/- 1.78%, 31.55% +/- 3.65%, and
      94.57% +/- 3.11% after 6 days, respectively. Besides, OA-4 was further
      investigated in a duck model with DHBV infection. When OA-4 was administered at a
      dosage of 500 mg/kg, the results revealed a significant inhibitory effects of
      DHBV at 19.94% +/- 2.87%, 28.80% +/- 3.62% and 29.25% +/- 2.65% at days 5, 10,
      and 3 after the cessation of OA-4 treatment, respectively. It's worth noting that
      OA-4 is superior to lamivudine in the inhibition of rebound of viral replication
      rate. The structure-activity relationships of OA derivatives had been preliminary
      discussed, which should be useful to explore further novel anti-HBV agents. 

PMID- 27023499
TI  - Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase
      Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy.
AB  - Herein we describe the synthesis and in vitro biological evaluation of thirteen
      new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic,
      multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1
      methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1
      one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but
      moderately potent EeAChE inhibitor (IC50 = 38.7 +/- 1.7 MUM), and a very potent
      antioxidant agent on the basis of the ORAC test (2.31 +/- 0.29 MUmol.Trolox/MUmol
      compound). 

PMID- 27023500
TI  - Protective Effect of a (Poly)phenol-Rich Extract Derived from Sweet Cherries
      Culls against Oxidative Cell Damage.
AB  - Oxidative stress is one of the key phenomena behind the most common types of
      chronic diseases. Therefore, the modulation of oxidative stress is an interesting
      target for acting either through prevention or as a therapeutic approach. In this
      work, a Portuguese variety of cherry (Saco Cherry) was processed in order to
      obtain a potent in vitro antioxidant phenolic-rich extract (Ch-PRE), which was
      further explored to evaluate its potential application as nutraceutical agent
      against cellular oxidative stress damage. Ch-PRE was mainly composed of
      anthocyanins, particularly cyanidin-3-rutinoside, cyanidin-3-glucoside, peonidin
      3-glucoside and neochlorogenic acid, and exhibited a potent chemical antioxidant
      activity expressed by its oxygen radical absorbance capacity (ORAC) and hydroxyl
      radical averting capacity (HORAC) values. Ch-PRE also displayed effective
      intracellular radical scavenging properties in intestinal epithelial and neuronal
      cells challenged with oxidative stress but showed a different order of
      effectiveness regarding the modulation of endogenous antioxidant system. Ch-PRE
      could be an attractive candidate to formulate an agent for the prevention of
      oxidative stress-induced disorders such as intestinal inflammation disorders or
      with an appropriated delivery system for neurodegenerative diseases. 

PMID- 27023501
TI  - The Tissue Distribution and Urinary Excretion Study of Gallic Acid and
      Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in
      Rats.
AB  - In the present study, we investigated the tissue distribution and urinary
      excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral
      administration of aqueous extract of Polygonum capitatum (P. capitatum, named
      Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed
      and adopted for quantification of GA and PCA in different tissue homogenate and
      urine samples. Interestingly, we found that GA and PCA showed a relatively
      targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract
      (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and
      PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at
      one hour after oral administration. The results helped explain the empirical use
      of P. capitatum for kidney diseases in folk medicine. Further studies on urinary
      excretion of P. capitatum extract indicated that GA and PCA followed a
      concentrated elimination over a 4-h period. The predominant metabolites were
      putatively identified to be 4-methylgallic acid (4-OMeGA) and 4
      methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and
      characteristic fragment ions using tandem mass spectrometry. However, the amount
      of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72%
      of the total intake, respectively, which is reported for the first time in this
      study. 

PMID- 27023502
TI  - From Nanorods to Nanowires of CdS Synthesized by a Solvothermal Method: Influence
      of the Morphology on the Photoactivity for Hydrogen Evolution from Water.
AB  - The effect of temperature and water/thiourea ratio on the growth, crystallinity
      and morphological characteristics of CdS nanostructures synthetized by a
      solvothermal method using ethylenediamine as solvent were studied. The
      temperature and water/thiourea ratio used in the synthesis determine the surface
      area, shape, length and degree of crystallinity of the CdS nanostructures
      obtained. Nanowires of high crystallinity and length were obtained when the
      solvothermal synthesis was performed at 190  degrees C, while nanorods with lower
      length and crystallinity were obtained as the solvothermal temperature decreased
      to 120  degrees C. The change in the water/thiourea ratio affects the
      crystallinity and length of the CdS nanostructures to a lesser extent than
      temperature. Nevertheless an increase in the water/thiourea ratio used during the
      solvothermal synthesis resulted in CdS nanorods with higher crystallinity, lower
      aspect ratio and lower specific surface area. Textural, structural and surface
      properties of the prepared CdS nanostructures were determined and related to the
      activity results in the production of hydrogen from aqueous solutions containing
      SO3(2-) + S(2-) under visible light.

PMID- 27023503
TI  - Effect of Drying Methods on the Steroidal Alkaloid Content of Potato Peels,
      Shoots and Berries.
AB  - The present study has found that dried potato samples yielded significantly
      higher levels of steroidal alkaloids such as alpha-solanine and alpha-chaconine
      than the corresponding fresh samples, as determined by the UPLC-MS/MS technique.
      Among the drying techniques used, air drying had the highest effect on steroidal
      alkaloid contents, followed by freeze drying and vacuum oven drying. There was no
      significant difference between the freeze dried and vacuum oven dried samples in
      their alpha-chaconine contents. However, freeze dried potato shoots and berries
      had significantly higher alpha-solanine contents (825 ug/g dry weight (DW) in
      shoots and 2453 ug/g DW in berries) than the vacuum oven dried ones (325 ug/g dry
      weight (DW) in shoots and 2080 ug/g DW in berries). The kinetics of steroidal
      alkaloid contents of potato shoots during air drying were monitored over a period
      of 21 days. Both alpha-solanine and alpha-chaconine content increased to their
      maximum values, 875 ug/g DW and 3385 ug/g DW, respectively, after 7 days of
      drying. The steroidal alkaloid contents of the shoots decreased significantly at
      day 9, and then remained unchanged until day 21. In line with the potato shoots,
      air dried potato tuber peels also had higher steroidal alkaloid content than the
      freeze dried and vacuum oven dried samples. However, a significant decrease of
      steroidal alkaloid content was observed in air dried potato berries, possibly due
      to degradation during slicing of the whole berries prior to air drying.
      Remarkable variation in steroidal alkaloid contents among different tissue types
      of potato plants was observed with the potato flowers having the highest content.

PMID- 27023504
TI  - The Chemical Composition of Achillea wilhelmsii C. Koch and Its Desirable Effects
      on Hyperglycemia, Inflammatory Mediators and Hypercholesterolemia as Risk Factors
      for Cardiometabolic Disease.
AB  - This study was done to identify the content compounds of Achillea wilhelmsii (A.
      wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic
      activity and effect on inflammatory mediators. The extracts and fractions of A.
      wilhelmsii were thoroughly analyzed using high performance liquid chromatography
      (HPLC), and the total content of phenols and flavonoids was determined. The
      hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice.
      The effect upon inflammatory mediators was evaluated in vitro using the human
      monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was
      evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase
      assay kit. The water extract (WE)-treated group showed the highest reduction in
      the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl
      acetate fraction (EAF) both showed a significant ability to reduce the secretion
      of tumor necrosis factor alpha (TNF-alpha). The EAF, however, also attenuated the
      levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP
      9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase
      (HMGR) inhibition activity. The five main compounds in the CF were isolated and
      identified. Out of the five compounds in the CF, 1beta,10beta
      epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti
      hypercholesterolemic potential. A molecular docking study provided corresponding
      results. 

PMID- 27023505
TI  - Synthesis of Ethano-Bridged Diazapolycenes as Potential Precursors for
      Diazapolycenes and Their Properties.
AB  - A series of ethanodiazapolycenes were prepared in 87%-89% yields by Friedlander
      reactions of three o-aminoarenecarbaldehydes with bicyclo[2.2.2]octane-2,5-dione
      and their spectral, thermal, and structural properties were studied. Subsequent
      attempts to convert them to diazapolycenes have proved unsuccessful. 

PMID- 27023506
TI  - Robust Synthesis of Ciprofloxacin-Capped Metallic Nanoparticles and Their Urease
      Inhibitory Assay.
AB  - The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap
      metallic (silver and gold) nanoparticles by a robust one pot synthetic method
      under optimized conditions, using NaBH4 as a mild reducing agent. Metallic
      nanoparticles (MNPs) showed constancy against variations in pH, table salt (NaCl)
      solution, and heat. Capping with metal ions (Ag/Au-cip) has significant
      implications for the solubility, pharmacokinetics and bioavailability of
      fluoroquinolone molecules. The metallic nanoparticles were characterized by
      several techniques such as ultraviolet visible spectroscopy (UV), atomic force
      microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), scanning
      electron microscopy (SEM) and energy dispersive X-ray (EDX) methods. The
      nanoparticles synthesized using silver and gold were subjected to energy
      dispersive X-ray tests in order to show their metallic composition. The NH moiety
      of the piperazine group capped the Ag/Au surfaces, as revealed by spectroscopic
      studies. The synthesized nanoparticles were also assessed for urease inhibition
      potential. Fascinatingly, both Ag-cip and Au-cip NPs exhibited significant urease
      enzyme inhibitory potential, with IC50 = 1.181 +/- 0.02 ug/mL and 52.55 +/- 2.3
      ug/mL, compared to ciprofloxacin (IC50 = 82.95 +/- 1.62 ug/mL). MNPs also
      exhibited significant antibacterial activity against selected bacterial strains. 

PMID- 27023507
TI  - Simultaneous Quantitation of Free Amino Acids, Nucleosides and Nucleobases in
      Sipunculus nudus by Ultra-High Performance Liquid Chromatography with Triple
      Quadrupole Mass Spectrometry.
AB  - To evaluate the nutritional and functional value of Sipunculus nudus, a rapid,
      simple and sensitive analytical method was developed using ultra-high performance
      liquid chromatography coupled with a triple quadrupole mass detection in multiple
      reaction monitoring mode for the simultaneous quantitative determination of 25
      free amino acids and 16 nucleosides and nucleobases in S. nudus within 20 min,
      which was confirmed to be reproducible and accurate. The limits of detection
      (LODs) and quantification (LOQs) were between 0.003-0.229 MUg/mL and 0.008-0.763
      MUg/mL for the 41 analytes, respectively. The established method was applied to
      analyze 19 batches of S. nudus samples from four habitats with two different
      processing methods. The results showed that S. nudus contained a variety of free
      amino acids, nucleosides and nucleobases in sufficient quantity and reasonable
      proportion. They also demonstrated that the contents of these compounds in
      different parts of S. nudus were significantly discriminating, which were in the
      order: (highest) coelomic fluid > body wall > intestine (lowest). The method is
      simple and accurate, and could serve as a technical support for establishing
      quality control of S. nudus and other functional seafoods. Moreover, the research
      results also laid foundation for further exploitation and development of S.
      nudus. 

PMID- 27023509
TI  - In-Vitro Anticancer Evaluation of Some Novel Thioureido-Benzensulfonamide
      Derivatives.
AB  - A novel series of sulfonamide derivatives (14 compounds) bearing thiourea
      moieties were efficiently synthesized and evaluated for their possible in vitro
      anticancer activity against four human tumor cell lines. The results indicated
      that compound 6 was the most potent, showing effectiveness on all the tested cell
      lines. Compounds 7 and 10 also showed promising results. 

PMID- 27023508
TI  - Mechanistic Insight of Bivalent Compound 21MO as Potential Neuroprotectant for
      Alzheimer's Disease.
AB  - We have recently developed a bivalent strategy to provide novel compounds that
      potentially target multiple risk factors involved in the development of
      Alzheimer's disease (AD). Our previous studies employing a bivalent compound with
      a shorter spacer (17MN) implicated that this compound can localize into
      mitochondria and endoplasmic reticulum (ER), thus interfering with the change of
      mitochondria membrane potential (MMP) and Ca(2+) levels in MC65 cells upon
      removal of tetracycline (TC). In this report, we examined the effects by a
      bivalent compound with a longer spacer (21MO) in MC65 cells. Our results
      demonstrated that 21MO suppressed the change of MMP, possibly via interaction
      with the mitochondrial complex I in MC65 cells. Interestingly, 21MO did not show
      any effects on the Ca(2+) level upon TC removal in MC65 cells. Our previous
      studies suggested that the mobilization of Ca(2+) in MC65 cells, upon withdraw of
      TC, originated from ER, so the results implicated that 21MO may preferentially
      interact with mitochondria in MC65 cells under the current experimental
      conditions. Collectively, the results suggest that bivalent compounds with varied
      spacer length and cell membrane anchor moiety may exhibit neuroprotective
      activities via different mechanisms of action. 

PMID- 27023510
TI  - Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric,
      Multiple Ligands Targeting Cholinesterases and Amyloid Beta.
AB  - Cholinesterases and amyloid beta are one of the major biological targets in the
      search for a new and efficacious treatment of Alzheimer's disease. The study
      describes synthesis and pharmacological evaluation of new compounds designed as
      dual binding site acetylcholinesterase inhibitors. Among the synthesized
      compounds, two deserve special attention--compounds 42 and 13. The former is a
      saccharin derivative and the most potent and selective acetylcholinesterase
      inhibitor (EeAChE IC50 = 70 nM). Isoindoline-1,3-dione derivative 13 displays
      balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE)
      (EeAChE IC50 = 0.76 MUM, EqBuChE IC50 = 0.618 MUM), and it inhibits amyloid beta
      aggregation (35.8% at 10 MUM). Kinetic studies show that the developed compounds
      act as mixed or non-competitive acetylcholinesterase inhibitors. According to
      molecular modelling studies, they are able to interact with both catalytic and
      peripheral active sites of the acetylcholinesterase. Their ability to cross the
      blood-brain barrier (BBB) was confirmed in vitro in the parallel artificial
      membrane permeability BBB assay. These compounds can be used as a solid starting
      point for further development of novel multifunctional ligands as potential anti
      Alzheimer's agents.

PMID- 27023511
TI  - Microwave-Assisted gamma-Valerolactone Production for Biomass Lignin Extraction:
      A Cascade Protocol.
AB  - The general need to slow the depletion of fossil resources and reduce carbon
      footprints has led to tremendous effort being invested in creating "greener"
      industrial processes and developing alternative means to produce fuels and
      synthesize platform chemicals. This work aims to design a microwave-assisted
      cascade process for a full biomass valorisation cycle. GVL (gamma-valerolactone),
      a renewable green solvent, has been used in aqueous acidic solution to achieve
      complete biomass lignin extraction. After lignin precipitation, the levulinic
      acid (LA)-rich organic fraction was hydrogenated, which regenerated the starting
      solvent for further biomass delignification. This process does not requires a
      purification step because GVL plays the dual role of solvent and product, while
      the reagent (LA) is a product of biomass delignification. In summary, this bio
      refinery approach to lignin extraction is a cascade protocol in which the solvent
      loss is integrated into the conversion cycle, leading to simplified methods for
      biomass valorisation. 

PMID- 27023512
TI  - Effect of Genotype and Environment on Salvia miltiorrhiza Roots Using LC/MS-Based
      Metabolomics.
AB  - Salvia miltiorrhiza (S. miltiorrhiza) Bunge is broadly used as herbal medicine
      for the clinical treatments of cardiovascular and cerebrovascular diseases.
      Despite its commercial and medicinal values, few systematic studies on the
      metabolome of S. miltiorrhiza roots have been carried out so far. We
      systematically described the metabolic profiles of S. miltiorrhiza using high
      pressure liquid chromatography mass spectrometry (LC/MS) in conjunction with
      multivariate statistical analyses, aimed at monitoring their biological
      variations of secondary metabolites related to three locations and four S.
      miltiorrhiza genotypes. A total of 40 bioactive constituents were putatively
      annotated in S. miltiorrhiza root samples. This study found that both the same S.
      miltiorrhiza genotype growing at three different locations and four S.
      miltiorrhiza genotypes growing at the same location had significant metabonomic
      differences identified by the principal component analysis (PCA) approach. By
      using orthogonal projection to latent structure with discriminant analysis (OPLS
      DA), 16 and 14 secondary metabolites can be used as potential location-specific
      and genotype-specific markers in S. miltiorrhiza, respectively. The specificity
      of LC/MS profiles offered a powerful tool to discriminate S. miltiorrhiza samples
      according to genotypes or locations. 

PMID- 27023513
TI  - Purification and Characterization of a White Laccase with Pronounced Dye
      Decolorizing Ability and HIV-1 Reverse Transcriptase Inhibitory Activity from
      Lepista nuda.
AB  - A strain LN07 with high laccase yield was identified as basidiomycete fungus
      Lepista nuda from which a white laccase without type I copper was purified and
      characterized. The laccase was a monomeric protein with a molecular mass of 56
      kDa. Its N-terminal amino acid sequence was AIGPAADLHIVNKDISPDGF. Besides, eight
      inner peptide sequences were determined and lac4, lac5 and lac6 sequences were in
      the Cu(2+) combination and conservation zones of laccases. HIV-1 reverse
      transcriptase was inhibited by the laccase with a half-inhibitory concentration
      of 0.65 MUM. Cu(2+) ions (1.5 mM) enhanced the laccase production and the optimal
      pH and temperature of the laccase were pH 3.0 and 50  degrees C, respectively.
      The Km and Vmax of the laccase using ABTS as substrate were respectively 0.19 mM
      and 195 MUM. Several dyes including laboratory dyes and textile dyes used in this
      study, such as Methyl red, Coomassie brilliant blue, Reactive brilliant blue and
      so on, were decolorized in different degrees by the purified laccase. By LC-MS
      analysis, Methyl red was structurally degraded by the laccase. Moreover, the
      laccase affected the absorbance at the maximum wavelength of many pesticides.
      Thus, the white laccase had potential commercial value for textile finishing and
      wastewater treatment. 

PMID- 27023514
TI  - Antibacterial Properties and Effects of Fruit Chilling and Extract Storage on
      Antioxidant Activity, Total Phenolic and Anthocyanin Content of Four Date Palm
      (Phoenix dactylifera) Cultivars.
AB  - Phoenix dactylifera or date palm fruits are reported to contain natural compounds
      that exhibit antioxidant and antibacterial properties. This research aimed to
      study the effect of fruit chilling at 4  degrees C for 8 weeks, extract storage
      at -20  degrees C for 5 weeks, and extraction solvents (methanol or acetone) on
      total phenolic content (TPC), antioxidant activity and antibacterial properties
      of Saudi Arabian P. dactylifera cv Mabroom, Safawi and Ajwa, as well as Iranian
      P. dactylifera cv Mariami. The storage stability of total anthocyanin content
      (TAC) was also evaluated, before and after storing the extracts at -20  degrees C
      and 4  degrees C respectively, for 5 weeks. Mariami had the highest TAC (3.18 +/-
      1.40 mg cyd 3-glu/100 g DW) while Mabroom had the lowest TAC (0.54 +/- 0.15 mg
      cyd 3-glu/100 g DW). The TAC of all extracts increased after storage. The
      chilling of date palm fruits for 8 weeks prior to solvent extraction elevated the
      TPC of all date fruit extracts, except for methanolic extracts of Mabroom and
      Mariami. All IC50 values of all cultivars decreased after the fruit chilling
      treatment. Methanol was a better solvent compared to acetone for the extraction
      of phenolic compounds in dates. The TPC of all cultivars extracts decreased after
      5 weeks of extract storage. IC50 values of all cultivars extracts increased after
      extract storage except for the methanolic extracts of Safawi and Ajwa. Different
      cultivars exhibited different antibacterial properties. Only the methanolic
      extract of Ajwa exhibited antibacterial activity against all four bacteria
      tested: Staphylococcus aureus, Bacillus cereus, Serratia marcescens and
      Escherichia coli. These results could be useful to the nutraceutical and
      pharmaceutical industries in the development of natural compound-based products. 

PMID- 27023515
TI  - Monocyte Subsets and Related Chemokines in Carotid Artery Stenosis and Ischemic
      Stroke.
AB  - Carotid stenosis (CS) is an important cause of ischemic stroke. However, reliable
      markers for the purpose of identification of high-risk, so-called vulnerable
      carotid plaques, are still lacking. Monocyte subsets are crucial players in
      atherosclerosis and might also contribute to plaque rupture. In this study we,
      therefore, aimed to investigate the potential role of monocyte subsets and
      associated chemokines as clinical biomarkers for vulnerability of CS. Patients
      with symptomatic and asymptomatic CS (n = 21), patients with cardioembolic
      ischemic strokes (n = 11), and controls without any cardiovascular disorder (n =
      11) were examined. Cardiovascular risk was quantified using the Essen Stroke Risk
      Score (ESRS). Monocyte subsets in peripheral blood were measured by quantitative
      flow cytometry. Plaque specimens were histologically analyzed. Furthermore,
      plasma levels of monocyte chemotactic protein 1 (MCP-1) and fractalkine were
      measured. Intermediate monocytes (Mon2) were significantly elevated in
      symptomatic and asymptomatic CS-patients compared to controls. Mon2 counts
      positively correlated with the ESRS. Moreover, stroke patients showed an
      elevation of Mon2 compared to controls, independent of the ESRS. MCP-1 levels
      were significantly higher in patients with symptomatic than in those with
      asymptomatic CS. Several histological criteria significantly differed between
      symptomatic and asymptomatic plaques. However, there was no association of
      monocyte subsets or chemokines with histological features of plaque
      vulnerability. Due to the multifactorial influence on monocyte subsets, the
      usability as clinical markers for plaque vulnerability seems to be limited.
      However, monocyte subsets may be critically involved in the pathology of CS. 

PMID- 27023516
TI  - Mechanical and IL-1beta Responsive miR-365 Contributes to Osteoarthritis
      Development by Targeting Histone Deacetylase 4.
AB  - Mechanical stress plays an important role in the initiation and progression of
      osteoarthritis. Studies show that excessive mechanical stress can directly damage
      the cartilage extracellular matrix and shift the balance in chondrocytes to favor
      catabolic activity over anabolism. However, the underlying mechanism remains
      unknown. MicroRNAs (miRNAs) are emerging as important regulators in
      osteoarthritis pathogenesis. We have found that mechanical loading up-regulated
      microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte
      differentiation. Here, we explored the role of the mechanical responsive microRNA
      miR-365 in pathogenesis of osteoarthritis (OA). We found that miR-365 was up
      regulated by cyclic loading and IL-1beta stimulation in articular chondrocytes
      through a mechanism that involved the transcription factor NF-kappaB. miR-365
      expressed significant higher level in rat anterior cruciate ligament (ACL)
      surgery induced OA cartilage as well as human OA cartilage from primary OA
      patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes
      increases gene expression of matrix degrading enzyme matrix metallopeptidase 13
      (MMP13) and collagen type X (Col X). The increase in miR-365 expression in OA
      cartilage and in response to IL-1 may contribute to the abnormal gene expression
      pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1beta
      induced MMP13 and Col X gene expression. We further showed histone deacetylase 4
      (HDAC4) is a direct target of miR-365, which mediates mechanical stress and
      inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of
      mechanical stress and pro-inflammatory responses, which contributes cartilage
      catabolism. Manipulation of the expression of miR-365 in articular chondrocytes
      by miR-365 inhibitor may be a potent therapeutic target for the prevention and
      treatment of osteoarthritis. 

PMID- 27023517
TI  - Molecular Characterization of MaCCS, a Novel Copper Chaperone Gene Involved in
      Abiotic and Hormonal Stress Responses in Musa acuminata cv. Tianbaojiao.
AB  - Copper/zinc superoxide dismutases (Cu/ZnSODs) play important roles in improving
      banana resistance to adverse conditions, but their activities depend on the
      copper chaperone for superoxide dismutase (CCS) delivering copper to them.
      However, little is known about CCS in monocots and under stress conditions. Here,
      a novel CCS gene (MaCCS) was obtained from a banana using reverse transcription
      PCR and rapid-amplification of cDNA ends (RACE) PCR. Sequence analyses showed
      that MaCCS has typical CCS domains and a conserved gene structure like other
      plant CCSs. Alternative transcription start sites (ATSSs) and alternative
      polyadenylation contribute to the mRNA diversity of MaCCS. ATSSs in MaCCS
      resulted in one open reading frame containing two in-frame start codons to form
      two protein versions, which is supported by the MaCCS subcellular localization of
      in both cytosol and chloroplasts. Furthermore, MaCCS promoter was found to
      contain many cis-elements associated with abiotic and hormonal responses.
      Quantitative real-time PCR analysis showed that MaCCS was expressed in all tested
      tissues (leaves, pseudostems and roots). In addition, MaCCS expression was
      significantly induced by light, heat, drought, abscisic acid and indole-3-acetic
      acid, but inhibited by relatively high concentrations of CuSO4 and under cold
      treatment, which suggests that MaCCS is involved in abiotic and hormonal
      responses. 

PMID- 27023518
TI  - Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung
      Cancer.
AB  - (1) BACKGROUND: Transient receptor potential vanilloid 3 (TRPV3) is a member of
      the TRP channels family of Ca(2+)-permeant channels. The proteins of some TRP
      channels are highly expressed in cancer cells. This study aimed to assess the
      clinical significance and biological functions of TRPV3 in non-small cell lung
      cancer (NSCLC); (2) METHODS: Immunohistochemistry was used to detect the
      expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues.
      Western blot was used to detect the protein expressions of TRPV3, CaMKII, p
      CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA
      was used to deplete TRPV3 expression. A laser scanning confocal microscope was
      used to measure intracellular calcium concentration ([Ca(2+)]i). Flow cytometry
      was used to analyze cell cycle; (3) RESULTS: TRPV3 was overexpressed in 65 of 96
      (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001)
      and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with
      short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit
      lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease
      [Ca(2+)]i of lung cancer cells and arrest cell cycle at the G1/S boundary.
      Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII,
      CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) CONCLUSIONS: Our
      findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with
      lung cancer progression. TRPV3 activation could promote proliferation of lung
      cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC. 

PMID- 27023519
TI  - Screening for Neurocognitive Impairment in HIV-Infected Individuals at First
      Contact after HIV Diagnosis: The Experience of a Large Clinical Center in
      Northern Italy.
AB  - Neurocognitive disorders are emerging, probably underestimated, complications in
      HIV-infected people. The aim of the study was to assess neurocognitive profiles
      of newly detected HIV-infected patients. We performed an observational
      retrospective single-cohort study. Illiterates and patients with neurologic
      symptoms or previous psychiatric diagnosis were excluded. Neuropsychological
      profiles were assessed using a validated battery of neuropsychological tests. We
      included 206 patients; with males representing the majority of them (85%). Risk
      factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in
      39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous
      injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was
      11.1 years (SD--standard deviation--3.7). A high prevalence of HIV-associated
      neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients:
      particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%,
      mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in
      1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus
      (HBV) co-infection were factors independently associated with HAND in a
      multivariable logistic regression model. Our data suggest that patient-specific
      factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A
      complete neuropsychological screening must be recommended in all patients at HIV
      infection diagnosis.

PMID- 27023520
TI  - The Role of Ultrahigh Resolution Fourier Transform Mass Spectrometry (FT-MS) in
      Astrobiology-Related Research: Analysis of Meteorites and Tholins.
AB  - It is an important but also a challenging analytical problem to understand the
      chemical composition and structure of prebiotic organic matter that is present in
      extraterrestrial materials. Its formation, evolution and content in the building
      blocks ("seeds") for more complex molecules, such as proteins and DNA, are key
      questions in the field of exobiology. Ultrahigh resolution mass spectrometry is
      one of the best analytical techniques that can be applied because it provides
      reliable information on the chemical composition and structure of individual
      components of complex organic mixtures. Prebiotic organic material is delivered
      to Earth by meteorites or generated in laboratories in simulation (model)
      experiments that mimic space or atmospheric conditions. Recent representative
      examples for ultrahigh resolution mass spectrometry studies using Fourier
      transform (FT) mass spectrometers such as Orbitrap and ion cyclotron resonance
      (ICR) mass spectrometers are shown and discussed in the present article,
      including: (i) the analysis of organic matter of meteorites; (ii) modeling
      atmospheric processes in ICR cells; and (iii) the structural analysis of
      laboratory made tholins that might be present in the atmosphere and surface of
      Saturn's largest moon, Titan. 

PMID- 27023521
TI  - Knock-Down of Endogenous Bornavirus-Like Nucleoprotein 1 Inhibits Cell Growth and
      Induces Apoptosis in Human Oligodendroglia Cells.
AB  - Endogenous bornavirus-like nucleoprotein elements (EBLNs) have been discovered in
      the genomes of various animals including humans, whose functions have been seldom
      studied. To explore the biological functions of human EBLNs, we constructed a
      lentiviral vector expressing a short-hairpin RNA against human EBLN1, which
      successfully inhibited EBLN1 expression by above 80% in infected human
      oligodendroglia cells (OL cells). We found that EBLN1 silencing suppressed cell
      proliferation, induced G2/M phase arrest, and promoted apoptosis in OL cells.
      Gene expression profiling demonstrated that 1067 genes were up-regulated, and
      2004 were down-regulated after EBLN1 silencing. The top 10 most upregulated genes
      were PI3, RND3, BLZF1, SOD2, EPGN, SBSN, INSIG1, OSMR, CREB3L2, and MSMO1, and
      the top 10 most-downregulated genes were KRTAP2-4, FLRT2, DIDO1, FAT4, ESCO2,
      ZNF804A, SUV420H1, ZC3H4, YAE1D1, and NCOA5. Pathway analysis revealed that these
      differentially expressed genes were mainly involved in pathways related to the
      cell cycle, the mitogen-activated protein kinase pathway, p53 signaling, and
      apoptosis. The gene expression profiles were validated by using quantitative
      reverse transcription polymerase chain reaction (RT-PCR) for detecting these 20
      most-changed genes. Three genes closely related to glioma, RND3, OSMR, and
      CREB3L2, were significantly upregulated and might be the key factors in EBLN1
      regulating the proliferation and apoptosis of OL cells. This study provides
      evidence that EBLN1 plays a key role in regulating cell life and death, thereby
      opening several avenues of investigation regarding EBLN1 in the future. 

PMID- 27023522
TI  - Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on
      Targeted Therapy.
AB  - Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic
      stem cell disorders characterized by cytopenia, ineffective hematopoiesis, and
      progression to secondary acute myeloid leukemia in high-risk cases. Conventional
      prognostication relies on clinicopathological parameters supplemented by
      cytogenetic information. However, recent studies have shown that genetic
      aberrations also have critical impacts on treatment outcome. Moreover, these
      genetic alterations may themselves be a target for treatment. The mutation
      landscape in MDS is shaped by gene aberrations involved in DNA methylation (TET2,
      DNMT3A, IDH1/2), histone modification (ASXL1, EZH2), the RNA splicing machinery
      (SF3B1, SRSF2, ZRSR2, U2AF1/2), transcription (RUNX1, TP53, BCOR, PHF6, NCOR,
      CEBPA, GATA2), tyrosine kinase receptor signaling (JAK2, MPL, FLT3, GNAS, KIT),
      RAS pathways (KRAS, NRAS, CBL, NF1, PTPN11), DNA repair (ATM, BRCC3, DLRE1C,
      FANCL), and cohesion complexes (STAG2, CTCF, SMC1A, RAD21). A detailed
      understanding of the pathogenetic mechanisms leading to transformation is
      critical for designing single-agent or combinatorial approaches in target therapy
      of MDS. 

PMID- 27023523
TI  - Targeted Disruption of Melanin Biosynthesis Genes in the Human Pathogenic Fungus
      Lomentospora prolificans and Its Consequences for Pathogen Survival.
AB  - The dematiaceous (melanised) fungus Lomentospora (Scedosporium) prolificans is a
      life-threatening opportunistic pathogen of immunocompromised humans, resistant to
      anti-fungal drugs. Melanin has been shown to protect human pathogenic fungi
      against antifungal drugs, oxidative killing and environmental stresses. To
      determine the protective role of melanin in L. prolificans to oxidative killing
      (H2O2), UV radiation and the polyene anti-fungal drug amphotericin B, targeted
      gene disruption was used to generate mutants of the pathogen lacking the
      dihydroxynaphthalene (DHN)-melanin biosynthetic enzymes polyketide synthase
      (PKS1), tetrahydroxynapthalene reductase (4HNR) and scytalone dehydratase (SCD1).
      Infectious propagules (spores) of the wild-type strain 3.1 were black/brown,
      whereas spores of the PKS-deficient mutant DeltaLppks1::hph were white.
      Complementation of the albino mutant DeltaLppks1::hph restored the black-brown
      spore pigmentation, while the 4HNR-deficient mutant DeltaLp4hnr::hph and SCD
      deficient mutant DeltaLpscd1::hph both produced orange-yellow spores. The mutants
      DeltaLppks1::hph and DeltaLp4hnr::hph showed significant reductions in spore
      survival following H2O2 treatment, while spores of DeltaLpscd1::hph and the
      DeltaLppks1::hph complemented strain DeltaLppks1::hph:PKS showed spore survivals
      similar to strain 3.1. Spores of the mutants DeltaLp4hnr::hph and
      DeltaLpscd1::hph and complemented strain DeltaLppks1::hph:PKS showed spore
      survivals similar to 3.1 following exposure to UV radiation, but survival of
      DeltaLppks1::hph spores was significantly reduced compared to the wild-type
      strain. Strain 3.1 and mutants DeltaLp4hnr::hph and DeltaLppks1::hph:PKS were
      resistant to amphotericin B while, paradoxically, the PKS1- and SCD1-deficient
      mutants showed significant increases in growth in the presence of the antifungal
      drug. Taken together, these results show that while melanin plays a protective
      role in the survival of the pathogen to oxidative killing and UV radiation,
      melanin does not contribute to its resistance to amphotericin B. 

PMID- 27023524
TI  - Species Identification of Bovine, Ovine and Porcine Type 1 Collagen; Comparing
      Peptide Mass Fingerprinting and LC-Based Proteomics Methods.
AB  - Collagen is one of the most ubiquitous proteins in the animal kingdom and the
      dominant protein in extracellular tissues such as bone, skin and other connective
      tissues in which it acts primarily as a supporting scaffold. It has been widely
      investigated scientifically, not only as a biomedical material for regenerative
      medicine, but also for its role as a food source for both humans and livestock.
      Due to the long-term stability of collagen, as well as its abundance in bone, it
      has been proposed as a source of biomarkers for species identification not only
      for heat- and pressure-rendered animal feed but also in ancient archaeological
      and palaeontological specimens, typically carried out by peptide mass
      fingerprinting (PMF) as well as in-depth liquid chromatography (LC)-based tandem
      mass spectrometric methods. Through the analysis of the three most common
      domesticates species, cow, sheep, and pig, this research investigates the
      advantages of each approach over the other, investigating sites of sequence
      variation with known functional properties of the collagen molecule. Results
      indicate that the previously identified species biomarkers through PMF analysis
      are not among the most variable type 1 collagen peptides present in these
      tissues, the latter of which can be detected by LC-based methods. However, it is
      clear that the highly repetitive sequence motif of collagen throughout the
      molecule, combined with the variability of the sites and relative abundance
      levels of hydroxylation, can result in high scoring false positive peptide
      matches using these LC-based methods. Additionally, the greater alpha 2(I) chain
      sequence variation, in comparison to the alpha 1(I) chain, did not appear to be
      specific to any particular functional properties, implying that intra-chain
      functional constraints on sequence variation are not as great as inter-chain
      constraints. However, although some of the most variable peptides were only
      observed in LC-based methods, until the range of publicly available collagen
      sequences improves, the simplicity of the PMF approach and suitable range of
      peptide sequence variation observed makes it the ideal method for initial
      taxonomic identification prior to further analysis by LC-based methods only when
      required. 

PMID- 27023525
TI  - The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and
      Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress
      Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO).
AB  - Carbon monoxide (CO) produced by heme oxygenase (HO)-1 and HO-2 or released from
      the CO-donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) causes
      vasodilation, with unknown efficacy against stress-induced gastric lesions. We
      studied whether pretreatment with CORM-2 (0.1-10 mg/kg oral gavage (i.g.)), RuCl3
      (1 mg/kg i.g.), zinc protoporphyrin IX (ZnPP) (10 mg/kg intraperitoneally
      (i.p.)), hemin (1-10 mg/kg i.g.) and CORM-2 (1 mg/kg i.g.) combined with N(G)
      nitro-l-arginine (l-NNA, 20 mg/kg i.p.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ, 10 mg/kg i.p.), indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.), and
      celecoxib (10 mg/kg i.g.) affects gastric lesions following 3.5 h of water
      immersion and restraint stress (WRS). Gastric blood flow (GBF), the number of
      gastric lesions and gastric CO and nitric oxide (NO) contents, blood
      carboxyhemoglobin (COHb) level and the gastric expression of HO-1, HO-2, hypoxia
      inducible factor 1alpha (HIF-1alpha), tumor necrosis factor alpha (TNF-alpha),
      cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) were determined. CORM-2
      (1 mg/kg i.g.) and hemin (10 mg/kg i.g.) significantly decreased WRS lesions
      while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was
      reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM
      2 decreased NO and increased HO-1 expression and CO and COHb content,
      downregulated HIF-1alpha, as well as WRS-elevated COX-2 and iNOS mRNAs.
      Gastroprotection by CORM-2 and HO depends upon CO's hyperemic and anti
      inflammatory properties, but is independent of NO. 

PMID- 27023526
TI  - The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular
      Mechanisms Differently Affected by Rab5a in the Early and Late Stages.
AB  - Autophagy favours metastatic growth through fuelling energy and nutrients and
      resistance to anoikis, typical of disseminated-tumour cells. The autophagic
      process, mediated by a unique organelle, the autophagosome, which fuses with
      lysosomes, is divided into three steps. Several stages, especially early
      omegasome formation and isolation-membrane initiation, remain controversial;
      molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle
      traffic for autophagosome formation. We examined Rab5a involvement in the
      function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated,
      interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was
      performed in human specimens of bone metastasis and pair-matched breast
      carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated
      in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231
      cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with
      Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were
      exposed to two inhibitors of autolysosome function, and LC3II and p62 expression
      was measured. We showed basal autophagy in bone-metastatic cells and the pivotal
      role of Rab5a together with Beclin 1 between the early stages, elongation of
      isolation membrane/closed autophagosome mediated by Atg7, and the late
      degradative stages. This regulatory network might occur in bone-metastasis and in
      high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring
      phenotypic characteristics for dissemination. 

PMID- 27023527
TI  - Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel
      Spacegroup at 1.83 A Resolution.
AB  - Kynurenine aminotransferase II (KAT-II) is a 47 kDa pyridoxal phosphate (PLP)
      dependent enzyme, active as a homodimer, which catalyses the transamination of
      the amino acids kynurenine (KYN) and 3-hydroxykynurenine (3-HK) in the tryptophan
      pathway, and is responsible for producing metabolites that lead to kynurenic acid
      (KYNA), which is implicated in several neurological diseases such as
      schizophrenia. In order to fully describe the role of KAT-II in the pathobiology
      of schizophrenia and other brain disorders, the crystal structure of full-length
      PLP-form hKAT-II was determined at 1.83 A resolution, the highest available. The
      electron density of the active site reveals an aldimine linkage between PLP and
      Lys263, as well as the active site residues, which characterize the fold-type I
      PLP-dependent enzymes. 

PMID- 27023528
TI  - Recurrent Fever in Children.
AB  - Children presenting with recurrent fever may represent a diagnostic challenge.
      After excluding the most common etiologies, which include the consecutive
      occurrence of independent uncomplicated infections, a wide range of possible
      causes are considered. This article summarizes infectious and noninfectious
      causes of recurrent fever in pediatric patients. We highlight that, when
      investigating recurrent fever, it is important to consider age at onset, family
      history, duration of febrile episodes, length of interval between episodes,
      associated symptoms and response to treatment. Additionally, information
      regarding travel history and exposure to animals is helpful, especially with
      regard to infections. With the exclusion of repeated independent uncomplicated
      infections, many infective causes of recurrent fever are relatively rare in
      Western countries; therefore, clinicians should be attuned to suggestive case
      history data. It is important to rule out the possibility of an infectious
      process or a malignancy, in particular, if steroid therapy is being considered.
      After excluding an infectious or neoplastic etiology, immune-mediated and
      autoinflammatory diseases should be taken into consideration. Together with case
      history data, a careful physical exam during and between febrile episodes may
      give useful clues and guide laboratory investigations. However, despite a
      thorough evaluation, a recurrent fever may remain unexplained. A watchful follow
      up is thus mandatory because new signs and symptoms may appear over time. 

PMID- 27023529
TI  - Fragment Screening of Human Aquaporin 1.
AB  - Aquaporins (AQPs) are membrane proteins that enable water transport across
      cellular plasma membranes in response to osmotic gradients. Phenotypic analyses
      have revealed important physiological roles for AQPs, and the potential for AQP
      water channel modulators in various disease states has been proposed. For
      example, AQP1 is overexpressed in tumor microvessels, and this correlates with
      higher metastatic potential and aggressiveness of the malignancy. Chemical
      modulators would help in identifying the precise contribution of water channel
      activity in these disease states. These inhibitors would also be important
      therapeutically, e.g., in anti-cancer treatment. This perceived importance
      contrasts with the lack of success of high-throughput screens (HTS) to identify
      effective and specific inhibitors of aquaporins. In this paper, we have screened
      a library of 1500 "fragments", i.e., smaller than molecules used in HTS, against
      human aquaporin (hAQP1) using a thermal shift assay and surface plasmon
      resonance. Although these fragments may not inhibit their protein target, they
      bound to and stabilized hAQP1 (sub mM binding affinities (KD), with an
      temperature of aggregation shift DeltaTagg of +4 to +50  degrees C) in a
      concentration-dependent fashion. Chemically expanded versions of these fragments
      should follow the determination of their binding site on the aquaporin surface. 

PMID- 27023530
TI  - Nutritional Signaling via Free Fatty Acid Receptors.
AB  - Excess energy is stored primarily as triglycerides, which are mobilized when
      demand for energy arises. Dysfunction of energy balance by excess food intake
      leads to metabolic diseases, such as obesity and diabetes. Free fatty acids
      (FFAs) provided by dietary fat are not only important nutrients, but also
      contribute key physiological functions via FFA receptor (FFAR)-mediated signaling
      molecules, which depend on FFAs' carbon chain length and the ligand specificity
      of the receptors. Functional analyses have revealed that FFARs are critical for
      metabolic functions, such as peptide hormone secretion and inflammation, and
      contribute to energy homeostasis. In particular, recent studies have shown that
      the administration of selective agonists of G protein-coupled receptor (GPR) 40
      and GPR120 improved glucose metabolism and systemic metabolic disorders.
      Furthermore, the anti-inflammation and energy metabolism effects of short chain
      FAs have been linked to the activation of GPR41 and GPR43. In this review, we
      summarize recent progress in research on FFAs and their physiological roles in
      the regulation of energy metabolism. 

PMID- 27023531
TI  - Role of Non-Coding RNAs in the Transgenerational Epigenetic Transmission of the
      Effects of Reprotoxicants.
AB  - Non-coding RNAs (ncRNAs) are regulatory elements of gene expression and chromatin
      structure. Both long and small ncRNAs can also act as inductors and targets of
      epigenetic programs. Epigenetic patterns can be transmitted from one cell to the
      daughter cell, but, importantly, also through generations. Diversity of ncRNAs is
      emerging with new and surprising roles. Functional interactions among ncRNAs and
      between specific ncRNAs and structural elements of the chromatin are drawing a
      complex landscape. In this scenario, epigenetic changes induced by environmental
      stressors, including reprotoxicants, can explain some transgenerationally
      transmitted phenotypes in non-Mendelian ways. In this review, we analyze
      mechanisms of action of reprotoxicants upon different types of ncRNAs and
      epigenetic modifications causing transgenerationally transmitted characters
      through germ cells but affecting germ cells and reproductive systems. A
      functional model of epigenetic mechanisms of transgenerational transmission
      ncRNAs-mediated is also proposed. 

PMID- 27023532
TI  - The Retentive Strength of Cemented Zirconium Oxide Crowns after Dentin
      Pretreatment with Desensitizing Paste Containing 8% Arginine and Calcium
      Carbonate.
AB  - The effect of dentin pretreatment with Desensitizing Paste containing 8% arginine
      and calcium carbonate on the retention of zirconium oxide (Y-TZP) crowns was
      tested. Forty molar teeth were mounted and prepared using a standardized
      protocol. Y-TZP crowns were produced using computer-aided design and computer
      aided manufacturing (CAD-CAM) technology. The 40 prepared teeth were either
      pretreated with Desensitizing Paste or not pretreated. After two weeks, each
      group was subdivided into two groups, cemented with either Resin Modified Glass
      Ionomer Cement (RMGIC) or Self Adhesive Resin Cement (SARC)). Prior to
      cementation, the surface areas of the prepared teeth were measured. After aging,
      the cemented crown-tooth assemblies were tested for retentive strength using a
      universal testing machine. The debonded surfaces of the teeth and crowns were
      examined microscopically at 10* magnification. Pretreating the dentin surfaces
      with Desensitizing Paste prior to cementation did not affect the retention of the
      Y-TZP crowns. The retentive values for RMGIC (3.04 +/- 0.77 MPa) were
      significantly higher than those for SARC (2.28 +/- 0.58 MPa). The predominant
      failure modes for the RMGIC and SARC were adhesive cement-dentin and adhesive
      cement-crown, respectively. An 8.0% arginine and calcium carbonate in-office
      desensitizing paste can be safely used to reduce post-cementation sensitivity
      without reducing the retentive strength of Y-TZP crowns. 

PMID- 27023534
TI  - Epigenetic Modifications in Essential Hypertension.
AB  - Essential hypertension (EH) is a complex, polygenic condition with no single
      causative agent. Despite advances in our understanding of the pathophysiology of
      EH, hypertension remains one of the world's leading public health problems.
      Furthermore, there is increasing evidence that epigenetic modifications are as
      important as genetic predisposition in the development of EH. Indeed, a complex
      and interactive genetic and environmental system exists to determine an
      individual's risk of EH. Epigenetics refers to all heritable changes to the
      regulation of gene expression as well as chromatin remodelling, without
      involvement of nucleotide sequence changes. Epigenetic modification is recognized
      as an essential process in biology, but is now being investigated for its role in
      the development of specific pathologic conditions, including EH. Epigenetic
      research will provide insights into the pathogenesis of blood pressure regulation
      that cannot be explained by classic Mendelian inheritance. This review
      concentrates on epigenetic modifications to DNA structure, including the
      influence of non-coding RNAs on hypertension development. 

PMID- 27023535
TI  - Infrared Irradiation: Toward Green Chemistry, a Review.
AB  - This review provides a comprehensive overview of where infrared irradiation has
      been employed, mainly as regards activating green mode for natural products
      extractions, as well as to favor a reaction, highlighting its actual importance.
      It is also underlined that infrared irradiation heating has been around for a
      long time; however, only in the last eighteen years have many of its advantages
      been applied to satisfy a wide range of chemical processes, natural products
      extractions, and for the promotion of many kinds of reactions. In addition, it is
      brought to light that near infrared irradiation is more efficient than middle and
      far infrared irradiations, being easily controllable and with the quality of a
      fast responding heat source. Thus, the main objective of this review is to offer
      infrared irradiation as an alternative clean energy source to activate reactions,
      in addition to favor the selective extraction of natural products, all of which
      is within the Green Chemistry protocol. Some recent results from our laboratory
      are also included. 

PMID- 27023536
TI  - Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation
      of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors TIMPs and Effect
      of HCV Protease Inhibitors.
AB  - An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with
      hepatitis C (HCV) infection. We measured the circulating levels of different MMPs
      and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the
      potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects.
      We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual
      or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV
      load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9,
      MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay
      Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed
      samples and their levels significantly increased in HCV monoinfected and HIV/HCV
      coinfected subjects compared to HD. TIMP-1 levels were significantly higher in
      HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness.
      These findings raise the possibility of using circulating TIMP-1 as a non
      invasive marker of liver fibrosis in HCV infection. A longitudinal study
      demonstrated that MMP-9 levels significantly decreased (40% reduction from
      baseline) in patients receiving dual as well as triple direct-acting antivirals
      (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the
      dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver,
      the decrease of MMP-9 following HCV protease inhibitor treatment suggests a
      positive effect on the reduction of liver inflammation. 

PMID- 27023533
TI  - Gut Microbiota and Lifestyle Interventions in NAFLD.
AB  - The human digestive system harbors a diverse and complex community of
      microorganisms that work in a symbiotic fashion with the host, contributing to
      metabolism, immune response and intestinal architecture. However, disruption of a
      stable and diverse community, termed "dysbiosis", has been shown to have a
      profound impact upon health and disease. Emerging data demonstrate dysbiosis of
      the gut microbiota to be linked with non-alcoholic fatty liver disease (NAFLD).
      Although the exact mechanism(s) remain unknown, inflammation, damage to the
      intestinal membrane, and translocation of bacteria have all been suggested.
      Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not
      all patients respond to these in the same manner. Furthermore, studies
      investigating the effects of lifestyle interventions on the gut microbiota in
      NAFLD patients are lacking. A deeper understanding of how different aspects of
      lifestyle (diet/nutrition/exercise) affect the host-microbiome interaction may
      allow for a more tailored approach to lifestyle intervention. With gut microbiota
      representing a key element of personalized medicine and nutrition, we review the
      effects of lifestyle interventions (diet and physical activity/exercise) on gut
      microbiota and how this impacts upon NAFLD prognosis. 

PMID- 27023537
TI  - Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome
      Related Endothelial Dysfunction in Hypertensive Patients.
AB  - Metabolic syndrome (MS) is characterized by an increased risk of incident
      diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and
      endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver
      disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic
      and inflammatory abnormalities. We addressed the question if the evolution in
      NAFLD might worsen endothelium-dependent vasodilating response in MS
      hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated
      hypertensive outpatients divided into three groups according to the
      presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were
      defined according to the National Cholesterol Education Program-Adult Treatment
      Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We
      determined IR by using the homeostasis model assessment (HOMA) index. Vascular
      function, as forearm blood flow (FBF), was determined through strain-gauge
      plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium
      nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular
      profiles compared with MS-NAFLD- and MS+NAFLD-. HOMA resulted in being the
      strongest predictor of FBF both in the MS+NAFLD- and in the MS+NAFLD+ groups,
      accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we
      demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent
      vasodilation compared with MS+NAFLD-, allowing for consideration of NAFLD as an
      early marker of endothelial dysfunction in hypertensives. 

PMID- 27023538
TI  - Estimation of Thermal Sensation Based on Wrist Skin Temperatures.
AB  - Thermal comfort is an essential environmental factor related to quality of life
      and work effectiveness. We assessed the feasibility of wrist skin temperature
      monitoring for estimating subjective thermal sensation. We invented a wrist band
      that simultaneously monitors skin temperatures from the wrist (i.e., the radial
      artery and ulnar artery regions, and upper wrist) and the fingertip. Skin
      temperatures from eight healthy subjects were acquired while thermal sensation
      varied. To develop a thermal sensation estimation model, the mean skin
      temperature, temperature gradient, time differential of the temperatures, and
      average power of frequency band were calculated. A thermal sensation estimation
      model using temperatures of the fingertip and wrist showed the highest accuracy
      (mean root mean square error [RMSE]: 1.26 +/- 0.31). An estimation model based on
      the three wrist skin temperatures showed a slightly better result to the model
      that used a single fingertip skin temperature (mean RMSE: 1.39 +/- 0.18). When a
      personalized thermal sensation estimation model based on three wrist skin
      temperatures was used, the mean RMSE was 1.06 +/- 0.29, and the correlation
      coefficient was 0.89. Thermal sensation estimation technology based on wrist skin
      temperatures, and combined with wearable devices may facilitate intelligent
      control of one's thermal environment. 

PMID- 27023539
TI  - Poly(3-Methylthiophene) Thin Films Deposited Electrochemically on QCMs for the
      Sensing of Volatile Organic Compounds.
AB  - Poly(3-methylthiophene) (PMeT) thin films were electrochemically deposited on
      quartz crystal microbalance QCM transducers to investigate their volatile organic
      compound (VOC) sensing properties depending on ambient conditions. Twelve
      different VOCs including alcohols, ketones, chlorinated compounds, amines, and
      the organosphosphate dimethyl methylphosphonate (DMMP) were used as analytes. The
      responses of the chemical sensors against DMMP were the highest among the tested
      analytes; thus, fabricated chemical sensors based on PMeT can be evaluated as
      potential candidates for selectively detecting DMMP. Generally, detection limits
      in the low ppm range could be achieved. The gas sensing measurements were
      recorded at various humid air conditions to investigate the effects of the
      humidity on the gas sensing properties. The sensing performance of the chemical
      sensors was slightly reduced in the presence of humidity in ambient conditions.
      While a decrease in sensitivity was observed for humidity levels up to 50% r.h.,
      the sensitivity was nearly unaffected for higher humidity levels and a reliable
      detection of the VOCs and DMMP was possible with detection limits in the low ppm
      range. 

PMID- 27023540
TI  - Secure Authentication for Remote Patient Monitoring with Wireless Medical Sensor
      Networks.
AB  - There is broad consensus that remote health monitoring will benefit all
      stakeholders in the healthcare system and that it has the potential to save
      billions of dollars. Among the major concerns that are preventing the patients
      from widely adopting this technology are data privacy and security. Wireless
      Medical Sensor Networks (MSNs) are the building blocks for remote health
      monitoring systems. This paper helps to identify the most challenging security
      issues in the existing authentication protocols for remote patient monitoring and
      presents a lightweight public-key-based authentication protocol for MSNs. In
      MSNs, the nodes are classified into sensors that report measurements about the
      human body and actuators that receive commands from the medical staff and perform
      actions. Authenticating these commands is a critical security issue, as any
      alteration may lead to serious consequences. The proposed protocol is based on
      the Rabin authentication algorithm, which is modified in this paper to improve
      its signature signing process, making it suitable for delay-sensitive MSN
      applications. To prove the efficiency of the Rabin algorithm, we implemented the
      algorithm with different hardware settings using Tmote Sky motes and also
      programmed the algorithm on an FPGA to evaluate its design and performance.
      Furthermore, the proposed protocol is implemented and tested using the MIRACL
      (Multiprecision Integer and Rational Arithmetic C/C++) library. The results show
      that secure, direct, instant and authenticated commands can be delivered from the
      medical staff to the MSN nodes. 

PMID- 27023542
TI  - Effect of Voltage Measurement on the Quantitative Identification of Transverse
      Cracks by Electrical Measurements.
AB  - Electrical tomography can be used as a structural health monitoring technique to
      identify different damage mechanisms in composite laminates. Previous work has
      established the link between transverse cracking density and mesoscale
      conductivity of the ply. Through the mesoscale relationship, the conductivity
      obtained from electrical tomography can be used as a measure of the transverse
      cracking density. Interpretation of this measure will be accurate provided the
      assumptions made during homogenization are valid. One main assumption of
      mesoscale homogenization is that the electric field is in the plane. Here, we
      test the validity of this assumption for laminates with varying anisotropy ratios
      and for different distances between the cracked ply and surface that is
      instrumented with electrodes. We also show the equivalence in electrical response
      between measurements from cracked laminates and their equivalent mesoscale
      counterparts. Finally, we propose some general guidelines on the measurement
      strategy for maximizing the accuracy of transverse cracks identification. 

PMID- 27023541
TI  - Amperometric Biosensor Based on Diamine Oxidase/Platinum
      Nanoparticles/Graphene/Chitosan Modified Screen-Printed Carbon Electrode for
      Histamine Detection.
AB  - This work describes the development and optimization studies of a novel biosensor
      employed in the detection and quantification of histamine in freshwater fish
      samples. The proposed biosensor is based on a modified carbon screen-printed
      electrode with diamineoxidase, graphene and platinum nanoparticles, which detects
      the hydrogen peroxide formed by the chemical process biocatalysed by the enzyme
      diamine oxidase and immobilized onto the nanostructurated surface of the receptor
      element. The amperometric measurements with the biosensor have been implemented
      in buffer solution of pH 7.4, applying an optimal low potential of +0.4 V. The
      novel biosensor shows high sensitivity (0.0631 MUA.MUM), low detection limit
      (2.54 * 10(-8) M) and a broad linear domain from 0.1 to 300 MUM. The
      applicability in natural complex samples and the analytical parameters of this
      enzyme sensor have been performed in the quantification of histamine in
      freshwater fish. An excellent correlation among results achieved with the
      developed biosensor and results found with the standard method for all freshwater
      fish samples has been achieved. 

PMID- 27023543
TI  - Complex Human Activity Recognition Using Smartphone and Wrist-Worn Motion
      Sensors.
AB  - The position of on-body motion sensors plays an important role in human activity
      recognition. Most often, mobile phone sensors at the trouser pocket or an
      equivalent position are used for this purpose. However, this position is not
      suitable for recognizing activities that involve hand gestures, such as smoking,
      eating, drinking coffee and giving a talk. To recognize such activities, wrist
      worn motion sensors are used. However, these two positions are mainly used in
      isolation. To use richer context information, we evaluate three motion sensors
      (accelerometer, gyroscope and linear acceleration sensor) at both wrist and
      pocket positions. Using three classifiers, we show that the combination of these
      two positions outperforms the wrist position alone, mainly at smaller
      segmentation windows. Another problem is that less-repetitive activities, such as
      smoking, eating, giving a talk and drinking coffee, cannot be recognized easily
      at smaller segmentation windows unlike repetitive activities, like walking,
      jogging and biking. For this purpose, we evaluate the effect of seven window
      sizes (2-30 s) on thirteen activities and show how increasing window size affects
      these various activities in different ways. We also propose various optimizations
      to further improve the recognition of these activities. For reproducibility, we
      make our dataset publicly available. 

PMID- 27023544
TI  - RheoStim: Development of an Adaptive Multi-Sensor to Prevent Venous Stasis.
AB  - Chronic venous insufficiency of the lower limbs is often underestimated and, in
      the absence of therapy, results in increasingly severe complications, including
      therapy-resistant tissue defects. Therefore, early diagnosis and adequate therapy
      is of particular importance. External counter pulsation (ECP) therapy is a method
      used to assist the venous system. The main principle of ECP is to squeeze the
      inner leg vessels by muscle contractions, which are evoked by functional
      electrical stimulation. A new adaptive trigger method is proposed, which improves
      and supplements the current therapeutic options by means of pulse synchronous
      electro-stimulation of the muscle pump. For this purpose, blood flow is
      determined by multi-sensor plethysmography. The hardware design and signal
      processing of this novel multi-sensor plethysmography device are introduced. The
      merged signal is used to determine the phase of the cardiac cycle, to ensure
      stimulation of the muscle pump during the filling phase of the heart. The pulse
      detection of the system is validated against a gold standard and provides a
      sensitivity of 98% and a false-negative rate of 2% after physical exertion.
      Furthermore, flow enhancement of the system has been validated by duplex
      ultrasonography. The results show a highly increased blood flow in the popliteal
      vein at the knee. 

PMID- 27023545
TI  - A Novel Tactile Sensor with Electromagnetic Induction and Its Application on
      Stick-Slip Interaction Detection.
AB  - Real-time detection of contact states, such as stick-slip interaction between a
      robot and an object on its end effector, is crucial for the robot to grasp and
      manipulate the object steadily. This paper presents a novel tactile sensor based
      on electromagnetic induction and its application on stick-slip interaction. An
      equivalent cantilever-beam model of the tactile sensor was built and capable of
      constructing the relationship between the sensor output and the friction applied
      on the sensor. With the tactile sensor, a new method to detect stick-slip
      interaction on the contact surface between the object and the sensor is proposed
      based on the characteristics of friction change. Furthermore, a prototype was
      developed for a typical application, stable wafer transferring on a wafer
      transfer robot, by considering the spatial magnetic field distribution and the
      sensor size according to the requirements of wafer transfer. The experimental
      results validate the sensing mechanism of the tactile sensor and verify its
      feasibility of detecting stick-slip on the contact surface between the wafer and
      the sensor. The sensing mechanism also provides a new approach to detect the
      contact state on the soft-rigid surface in other robot-environment interaction
      systems. 

PMID- 27023546
TI  - Fabrication of ZnO Nanowires Arrays by Anodization and High-Vacuum Die Casting
      Technique, and Their Piezoelectric Properties.
AB  - In this investigation, anodic aluminum oxide (AAO) with arrayed and regularly
      arranged nanopores is used as a template in the high-vacuum die casting of molten
      zinc metal (Zn) into the nanopores. The proposed technique yields arrayed Zn
      nanowires with an aspect ratio of over 600. After annealing, arrayed zinc oxide
      (ZnO) nanowires are obtained. Varying the anodizing time yields AAO templates
      with thicknesses of approximately 50 MUm, 60 MUm, and 70 MUm that can be used in
      the fabrication of nanowires of three lengths with high aspect ratios.
      Experimental results reveal that a longer nanowire generates a greater measured
      piezoelectric current. The ZnO nanowires that are fabricated using an alumina
      template are anodized for 7 h and produce higher piezoelectric current of up to
      69 pA. 

PMID- 27023547
TI  - Close-Range Tracking of Underwater Vehicles Using Light Beacons.
AB  - This paper presents a new tracking system for autonomous underwater vehicles
      (AUVs) navigating in a close formation, based on computer vision and the use of
      active light markers. While acoustic localization can be very effective from
      medium to long distances, it is not so advantageous in short distances when the
      safety of the vehicles requires higher accuracy and update rates. The proposed
      system allows the estimation of the pose of a target vehicle at short ranges,
      with high accuracy and execution speed. To extend the field of view, an
      omnidirectional camera is used. This camera provides a full coverage of the lower
      hemisphere and enables the concurrent tracking of multiple vehicles in different
      positions. The system was evaluated in real sea conditions by tracking vehicles
      in mapping missions, where it demonstrated robust operation during extended
      periods of time. 

PMID- 27023548
TI  - Capacity of Heterogeneous Mobile Wireless Networks with D-Delay Transmission
      Strategy.
AB  - This paper investigates the capacity problem of heterogeneous wireless networks
      in mobility scenarios. A heterogeneous network model which consists of n normal
      nodes and m helping nodes is proposed. Moreover, we propose a D-delay
      transmission strategy to ensure that every packet can be delivered to its
      destination nodes with limited delay. Different from most existing network
      schemes, our network model has a novel two-tier architecture. The existence of
      helping nodes greatly improves the network capacity. Four types of mobile
      networks are studied in this paper: i.i.d. fast mobility model and slow mobility
      model in two-dimensional space, i.i.d. fast mobility model and slow mobility
      model in three-dimensional space. Using the virtual channel model, we present an
      intuitive analysis of the capacity of two-dimensional mobile networks and three
      dimensional mobile networks, respectively. Given a delay constraint D, we derive
      the asymptotic expressions for the capacity of the four types of mobile networks.
      Furthermore, the impact of D and m to the capacity of the whole network is
      analyzed. Our findings provide great guidance for the future design of the next
      generation of networks. 

PMID- 27023549
TI  - Investigation on the Mechanical and Electrical Behavior of a Tuning Fork-Shaped
      Ionic Polymer Metal Composite Actuator with a Continuous Water Supply Mechanism.
AB  - This paper presents an innovative tuning fork-shaped ionic polymer metal
      composite (IPMC) actuator. With an integrated soft strain gauge and water supply
      mechanism (WSM), the surface strain of the actuator can be sensed in situ, and
      providing a continuous water supply maintains the water content inside the IPMC
      for long-term operation in air. The actuator was fabricated using a
      micromachining technique and plated with a nickel electrode. The device
      performance was experimentally characterized and compared with an actuator
      without a WSM. A large displacement of 1.5 mm was achieved for a 6 mm-long prong
      with 7-V dc actuation applied for 30 s. The measured current was analyzed using
      an electrochemical model. The results revealed that the faradaic current plays a
      crucial role during operation, particularly after 10 s. The measured strain
      confirms both the bending and axial strain generation during the open-and-close
      motion of the actuator prongs. Most of the water loss during device operation was
      due to evaporation rather than hydrolysis. The constructed WSM effectively
      maintained the water content inside the IPMC for long-term continuous operation. 

PMID- 27023550
TI  - Leaf Chlorophyll Content Estimation of Winter Wheat Based on Visible and Near
      Infrared Sensors.
AB  - The leaf chlorophyll content is one of the most important factors for the growth
      of winter wheat. Visual and near-infrared sensors are a quick and non-destructive
      testing technology for the estimation of crop leaf chlorophyll content. In this
      paper, a new approach is developed for leaf chlorophyll content estimation of
      winter wheat based on visible and near-infrared sensors. First, the sliding
      window smoothing (SWS) was integrated with the multiplicative scatter correction
      (MSC) or the standard normal variable transformation (SNV) to preprocess the
      reflectance spectra images of wheat leaves. Then, a model for the relationship
      between the leaf relative chlorophyll content and the reflectance spectra was
      developed using the partial least squares (PLS) and the back propagation neural
      network. A total of 300 samples from areas surrounding Yangling, China, were used
      for the experimental studies. The samples of visible and near-infrared
      spectroscopy at the wavelength of 450,900 nm were preprocessed using SWS, MSC and
      SNV. The experimental results indicate that the preprocessing using SWS and SNV
      and then modeling using PLS can achieve the most accurate estimation, with the
      correlation coefficient at 0.8492 and the root mean square error at 1.7216. Thus,
      the proposed approach can be widely used for winter wheat chlorophyll content
      analysis. 

PMID- 27023551
TI  - Spectroscopic Terahertz Imaging at Room Temperature Employing Microbolometer
      Terahertz Sensors and Its Application to the Study of Carcinoma Tissues.
AB  - A terahertz (THz) imaging system based on narrow band microbolometer sensors
      (NBMS) and a novel diffractive lens was developed for spectroscopic microscopy
      applications. The frequency response characteristics of the THz antenna-coupled
      NBMS were determined employing Fourier transform spectroscopy. The NBMS was found
      to be a very sensitive frequency selective sensor which was used to develop a
      compact all-electronic system for multispectral THz measurements. This system was
      successfully applied for principal components analysis of optically opaque packed
      samples. A thin diffractive lens with a numerical aperture of 0.62 was proposed
      for the reduction of system dimensions. The THz imaging system enhanced with
      novel optics was used to image for the first time non-neoplastic and neoplastic
      human colon tissues with close to wavelength-limited spatial resolution at 584
      GHz frequency. The results demonstrated the new potential of compact RT THz
      imaging systems in the fields of spectroscopic analysis of materials and medical
      diagnostics. 

PMID- 27023552
TI  - Improved Tuning Fork for Terahertz Quartz-Enhanced Photoacoustic Spectroscopy.
AB  - We report on a quartz-enhanced photoacoustic (QEPAS) sensor for methanol (CH3OH)
      detection employing a novel quartz tuning fork (QTF), specifically designed to
      enhance the QEPAS sensing performance in the terahertz (THz) spectral range. A
      discussion of the QTF properties in terms of resonance frequency, quality factor
      and acousto-electric transduction efficiency as a function of prong sizes and
      spacing between the QTF prongs is presented. The QTF was employed in a QEPAS
      sensor system using a 3.93 THz quantum cascade laser as the excitation source in
      resonance with a CH3OH rotational absorption line located at 131.054 cm(-1). A
      minimum detection limit of 160 ppb in 30 s integration time, corresponding to a
      normalized noise equivalent absorption NNEA = 3.75 * 10(-11) cm(-1)W/Hz(1/2), was
      achieved, representing a nearly one-order-of-magnitude improvement with respect
      to previous reports. 

PMID- 27023553
TI  - An Evaluation of Sensor Performance for Harmful Compounds by Using Photo-Induced
      Electron Transfer from Photosynthetic Membranes to Electrodes.
AB  - Rapid, simple, and low-cost screening procedures are necessary for the detection
      of harmful compounds in the effluent that flows out of point sources such as
      industrial outfall. The present study investigated the effects on a novel sensor
      of harmful compounds such as KCN, phenol, and herbicides such as 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU), 2-chloro-4-ethylamino-6-isopropylamino
      1,3,5-triazine (atrazine), and 2-N-tert-butyl-4-N-ethyl-6-methylsulfanyl-1,3,5
      triazine-2,4-diamine (terbutryn). The sensor employed an electrode system that
      incorporated the photocurrent of intra-cytoplasmic membranes (so-called
      chromatophores) prepared from photosynthetic bacteria and linked using carbon
      paste electrodes. The amperometric curve (photocurrent-time curve) of photo
      induced electron transfer from chromatophores of the purple photosynthetic
      bacterium Rhodobacter sphaeroides to the electrode via an exogenous electron
      acceptor was composed of two characteristic phases: an abrupt increase in current
      immediately after illumination (I0), and constant current over time (Ic).
      Compared with other redox compounds, 2,5-dichloro-1,4-benzoquinone (DCBQ) was the
      most useful exogenous electron acceptor in this system. Photo-reduction of DCBQ
      exhibited Michaelis-Menten-like kinetics, and reduction rates were dependent on
      the amount of DCBQ and the photon flux intensity. The Ic decreased in the
      presence of KCN at concentrations over 0.05 MUM (=MUmol.dm(-3)). The I0 decreased
      following the addition of phenol at concentrations over 20 MUM. The Ic was
      affected by terbutryn at concentrations over 10 MUM. In contrast, DCMU and
      atrazine had no effect on either I0 or Ic. The utility of this electrode system
      for the detection of harmful compounds is discussed. 

PMID- 27023554
TI  - Delay/Disruption Tolerant Network-Based Message Forwarding for a River Pollution
      Monitoring Wireless Sensor Network Application.
AB  - Communications from remote areas that may be of interest is still a problem. Many
      innovative projects applied to remote sites face communications difficulties. The
      GOLDFISH project was an EU-funded project for river pollution monitoring in
      developing countries. It had several sensor clusters, with floating WiFi
      antennas, deployed along a downstream river's course. Sensor clusters sent
      messages to a Gateway installed on the riverbank. This gateway sent the messages,
      through a backhaul technology, to an Internet server where data was aggregated
      over a map. The communication challenge in this scenario was produced by the
      antennas' movement and network backhaul availability. Since the antennas were
      floating on the river, communications could be disrupted at any time. Also, 2G/3G
      availability near the river was not constant. For non-real-time applications, we
      propose a Delay/Disruption Tolerant Network (DTN)-based solution where all nodes
      have persistent storage capabilities and DTN protocols to be able to wait minutes
      or hours to transmit. A mechanical backhaul will periodically visit the river
      bank where the gateway is installed and it will automatically collect sensor data
      to be carried to an Internet-covered spot. The proposed forwarding protocol
      delivers around 98% of the messages for this scenario, performing better than
      other well-known DTN routing protocols. 

PMID- 27023555
TI  - Penetration Depth Measurement of Near-Infrared Hyperspectral Imaging Light for
      Milk Powder.
AB  - The increasingly common application of the near-infrared (NIR) hyperspectral
      imaging technique to the analysis of food powders has led to the need for optical
      characterization of samples. This study was aimed at exploring the feasibility of
      quantifying penetration depth of NIR hyperspectral imaging light for milk powder.
      Hyperspectral NIR reflectance images were collected for eight different milk
      powder products that included five brands of non-fat milk powder and three brands
      of whole milk powder. For each milk powder, five different powder depths ranging
      from 1 mm-5 mm were prepared on the top of a base layer of melamine, to test
      spectral-based detection of the melamine through the milk. A relationship was
      established between the NIR reflectance spectra (937.5-1653.7 nm) and the
      penetration depth was investigated by means of the partial least squares
      discriminant analysis (PLS-DA) technique to classify pixels as being milk-only or
      a mixture of milk and melamine. With increasing milk depth, classification model
      accuracy was gradually decreased. The results from the 1-mm, 2-mm and 3-mm models
      showed that the average classification accuracy of the validation set for milk
      melamine samples was reduced from 99.86% down to 94.93% as the milk depth
      increased from 1 mm-3 mm. As the milk depth increased to 4 mm and 5 mm, model
      performance deteriorated further to accuracies as low as 81.83% and 58.26%,
      respectively. The results suggest that a 2-mm sample depth is recommended for the
      screening/evaluation of milk powders using an online NIR hyperspectral imaging
      system similar to that used in this study. 

PMID- 27023556
TI  - A Simple Interface for 3D Position Estimation of a Mobile Robot with Single
      Camera.
AB  - In recent years, there has been an increase in the number of mobile robots
      controlled by a smart phone or tablet. This paper proposes a visual control
      interface for a mobile robot with a single camera to easily control the robot
      actions and estimate the 3D position of a target. In this proposal, the mobile
      robot employed an Arduino Yun as the core processor and was remote-controlled by
      a tablet with an Android operating system. In addition, the robot was fitted with
      a three-axis robotic arm for grasping. Both the real-time control signal and
      video transmission are transmitted via Wi-Fi. We show that with a properly
      calibrated camera and the proposed prototype procedures, the users can click on a
      desired position or object on the touchscreen and estimate its 3D coordinates in
      the real world by simple analytic geometry instead of a complicated algorithm.
      The results of the measurement verification demonstrates that this approach has
      great potential for mobile robots. 

PMID- 27023557
TI  - Application of MEMS Accelerometers and Gyroscopes in Fast Steering Mirror Control
      Systems.
AB  - In a charge-coupled device (CCD)-based fast steering mirror (FSM) tracking
      control system, high control bandwidth is the most effective way to enhance the
      closed-loop performance. However, the control system usually suffers a great deal
      from mechanical resonances and time delays induced by the low sampling rate of
      CCDs. To meet the requirements of high precision and load restriction, fiber
      optic gyroscopes (FOGs) are usually used in traditional FSM tracking control
      systems. In recent years, the MEMS accelerometer and gyroscope are becoming
      smaller and lighter and their performance have improved gradually, so that they
      can be used in a fast steering mirror (FSM) to realize the stabilization of the
      line-of-sight (LOS) of the control system. Therefore, a tentative approach to
      implement a CCD-based FSM tracking control system, which uses MEMS accelerometers
      and gyroscopes as feedback components and contains an acceleration loop, a
      velocity loop and a position loop, is proposed. The disturbance suppression of
      the proposed method is the product of the error attenuation of the acceleration
      loop, the velocity loop and the position loop. Extensive experimental results
      show that the MEMS accelerometers and gyroscopes can act the similar role as the
      FOG with lower cost for stabilizing the LOS of the FSM tracking control system. 

PMID- 27023559
TI  - A Survey on Security and Privacy in Emerging Sensor Networks: From Viewpoint of
      Close-Loop.
AB  - Nowadays, as the next generation sensor networks, Cyber-Physical Systems (CPSs)
      refer to the complex networked systems that have both physical subsystems and
      cyber components, and the information flow between different subsystems and
      components is across a communication network, which forms a closed-loop. New
      generation sensor networks are found in a growing number of applications and have
      received increasing attention from many inter-disciplines. Opportunities and
      challenges in the design, analysis, verification and validation of sensor
      networks co-exists, among which security and privacy are two important
      ingredients. This paper presents a survey on some recent results in the security
      and privacy aspects of emerging sensor networks from the viewpoint of the closed
      loop. This paper also discusses several future research directions under these
      two umbrellas. 

PMID- 27023560
TI  - LS Channel Estimation and Signal Separation for UHF RFID Tag Collision Recovery
      on the Physical Layer.
AB  - In a passive ultra-high frequency (UHF) radio-frequency identification (RFID)
      system, tag collision is generally resolved on a medium access control (MAC)
      layer. However, some of collided tag signals could be recovered on a physical
      (PHY) layer and, thus, enhance the identification efficiency of the RFID system.
      For the recovery on the PHY layer, channel estimation is a critical issue. Good
      channel estimation will help to recover the collided signals. Existing channel
      estimates work well for two collided tags. When the number of collided tags is
      beyond two, however, the existing estimates have more estimation errors. In this
      paper, we propose a novel channel estimate for the UHF RFID system. It adopts an
      orthogonal matrix based on the information of preambles which is known for a
      reader and applies a minimum-mean-square-error (MMSE) criterion to estimate
      channels. From the estimated channel, we could accurately separate the collided
      signals and recover them. By means of numerical results, we show that the
      proposed estimate has lower estimation errors and higher separation efficiency
      than the existing estimates. 

PMID- 27023558
TI  - Balance Improvement Effects of Biofeedback Systems with State-of-the-Art Wearable
      Sensors: A Systematic Review.
AB  - Falls and fall-induced injuries are major global public health problems. Balance
      and gait disorders have been the second leading cause of falls. Inertial motion
      sensors and force sensors have been widely used to monitor both static and
      dynamic balance performance. Based on the detected performance, instant visual,
      auditory, electrotactile and vibrotactile biofeedback could be provided to
      augment the somatosensory input and enhance balance control. This review aims to
      synthesize the research examining the effect of biofeedback systems, with
      wearable inertial motion sensors and force sensors, on balance performance.
      Randomized and non-randomized clinical trials were included in this review. All
      studies were evaluated based on the methodological quality. Sample
      characteristics, device design and study characteristics were summarized. Most
      previous studies suggested that biofeedback devices were effective in enhancing
      static and dynamic balance in healthy young and older adults, and patients with
      balance and gait disorders. Attention should be paid to the choice of appropriate
      types of sensors and biofeedback for different intended purposes. Maximizing the
      computing capacity of the micro-processer, while minimizing the size of the
      electronic components, appears to be the future direction of optimizing the
      devices. Wearable balance-improving devices have their potential of serving as
      balance aids in daily life, which can be used indoors and outdoors. 

PMID- 27023562
TI  - A Sensitive Secondary Users Selection Algorithm for Cognitive Radio Ad Hoc
      Networks.
AB  - Secondary Users (SUs) are allowed to use the temporarily unused licensed spectrum
      without disturbing Primary Users (PUs) in Cognitive Radio Ad Hoc Networks
      (CRAHNs). Existing architectures for CRAHNs impose energy-consuming Cognitive
      Radios (CRs) on SUs. However, the advanced CRs will increase energy cost for
      their cognitive functionalities, which is undesirable for the battery powered
      devices. A new architecture referred to as spectral Requirement-based CRAHN
      (RCRAHN) is proposed to enhance energy efficiency for CRAHNs in this paper. In
      RCRAHNs, only parts of SUs are equipped with CRs. SUs equipped with CRs are
      referred to as Cognitive Radio Users (CRUs). To further enhance energy efficiency
      of CRAHNs, we aim to select minimum CRUs to sense available spectrum. A non
      linear programming problem is mathematically formulated under the constraints of
      energy efficiency and real-time. Considering the NP-hardness of the problem, a
      framework of a heuristic algorithm referred to as Sensitive Secondary Users
      Selection (SSUS) was designed to compute the near-optimal solutions. The
      simulation results demonstrate that SSUS not only improves the energy efficiency,
      but also achieves satisfied performances in end-to-end delay and communication
      reliability. 

PMID- 27023561
TI  - A Virtual Environment to Improve the Detection of Oral-Facial Malfunction in
      Children with Cerebral Palsy.
AB  - The importance of an early rehabilitation process in children with cerebral palsy
      (CP) is widely recognized. On the one hand, new and useful treatment tools such
      as rehabilitation systems based on interactive technologies have appeared for
      rehabilitation of gross motor movements. On the other hand, from the therapeutic
      point of view, performing rehabilitation exercises with the facial muscles can
      improve the swallowing process, the facial expression through the management of
      muscles in the face, and even the speech of children with cerebral palsy.
      However, it is difficult to find interactive games to improve the detection and
      evaluation of oral-facial musculature dysfunctions in children with CP. This
      paper describes a framework based on strategies developed for interactive serious
      games that is created both for typically developed children and children with
      disabilities. Four interactive games are the core of a Virtual Environment called
      SONRIE. This paper demonstrates the benefits of SONRIE to monitor children's oral
      facial difficulties. The next steps will focus on the validation of SONRIE to
      carry out the rehabilitation process of oral-facial musculature in children with
      cerebral palsy. 

PMID- 27023563
TI  - Concrete Condition Assessment Using Impact-Echo Method and Extreme Learning
      Machines.
AB  - The impact-echo (IE) method is a popular non-destructive testing (NDT) technique
      widely used for measuring the thickness of plate-like structures and for
      detecting certain defects inside concrete elements or structures. However, the IE
      method is not effective for full condition assessment (i.e., defect detection,
      defect diagnosis, defect sizing and location), because the simple frequency
      spectrum analysis involved in the existing IE method is not sufficient to capture
      the IE signal patterns associated with different conditions. In this paper, we
      attempt to enhance the IE technique and enable it for full condition assessment
      of concrete elements by introducing advanced machine learning techniques for
      performing comprehensive analysis and pattern recognition of IE signals.
      Specifically, we use wavelet decomposition for extracting signatures or features
      out of the raw IE signals and apply extreme learning machine, one of the recently
      developed machine learning techniques, as classification models for full
      condition assessment. To validate the capabilities of the proposed method, we
      build a number of specimens with various types, sizes, and locations of defects
      and perform IE testing on these specimens in a lab environment. Based on analysis
      of the collected IE signals using the proposed machine learning based IE method,
      we demonstrate that the proposed method is effective in performing full condition
      assessment of concrete elements or structures. 

PMID- 27023564
TI  - Pedestrian Detection and Tracking from Low-Resolution Unmanned Aerial Vehicle
      Thermal Imagery.
AB  - Driven by the prominent thermal signature of humans and following the growing
      availability of unmanned aerial vehicles (UAVs), more and more research efforts
      have been focusing on the detection and tracking of pedestrians using thermal
      infrared images recorded from UAVs. However, pedestrian detection and tracking
      from the thermal images obtained from UAVs pose many challenges due to the low
      resolution of imagery, platform motion, image instability and the relatively
      small size of the objects. This research tackles these challenges by proposing a
      pedestrian detection and tracking system. A two-stage blob-based approach is
      first developed for pedestrian detection. This approach first extracts pedestrian
      blobs using the regional gradient feature and geometric constraints filtering and
      then classifies the detected blobs by using a linear Support Vector Machine (SVM)
      with a hybrid descriptor, which sophisticatedly combines Histogram of Oriented
      Gradient (HOG) and Discrete Cosine Transform (DCT) features in order to achieve
      accurate detection. This research further proposes an approach for pedestrian
      tracking. This approach employs the feature tracker with the update of detected
      pedestrian location to track pedestrian objects from the registered videos and
      extracts the motion trajectory data. The proposed detection and tracking
      approaches have been evaluated by multiple different datasets, and the results
      illustrate the effectiveness of the proposed methods. This research is expected
      to significantly benefit many transportation applications, such as the multimodal
      traffic performance measure, pedestrian behavior study and pedestrian-vehicle
      crash analysis. Future work will focus on using fused thermal and visual images
      to further improve the detection efficiency and effectiveness. 

PMID- 27023565
TI  - Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of
      Acute and Recurrent Idiopathic Pericarditis.
AB  - Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay
      of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive
      review consisting of pertinent clinical literature, pharmacokinetic, and
      pharmacodynamic considerations, has not been released in recent years. This
      review will facilitate the clinician's understanding of pharmacotherapeutic
      considerations for using ASA/NSAIDs to treat IP. Data were compiled using
      clinical literature consisting of case reports, cohort data, retrospective and
      prospective studies, and manufacturer package inserts. ASA, ibuprofen,
      indometacin, and ketorolac relatively have the most evidence in the treatment of
      IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is
      the drug of choice in patients with coronary artery disease (CAD), heart failure
      (HF), or renal disease, but should be avoided in patients with asthma and nasal
      polyps, who are naive to ASA therapy. Ibuprofen is an inexpensive and relatively
      accessible option in patients who do not have concomitant CAD, HF, or renal
      disease. Indometacin is not available over-the-counter in the USA, and has a
      relatively higher incidence of central nervous system (CNS) adverse effects.
      Ketorolac is an intravenous option; however, clinicians must be mindful of the
      maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the
      disease process of IP, they are part of first-line therapy (along with
      colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated
      by comorbid conditions, tolerability, and adverse effects. Additionally, the
      clinician should be mindful of considerations such as tapering, high-sensitivity
      CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. 

PMID- 27023566
TI  - A Selenium Containing Inhibitor for the Treatment of Hepatocellular Cancer.
AB  - Hepatocellular carcinoma (HCC) is the third most deadly cancer in the world. New
      treatment strategies are desperately needed due to limited standard therapies.
      Activation of the Erk, Akt, and STAT3pathways is implicated in the prognosis of
      HCC. The Se,Se'-1,4-phenylenebis(1,2-ethanediyl) bisisoselenourea (PBISe), is a
      selenium-containing MAPK and PI3 kinase inhibitor, effectively inhibit
      tumorigenesis in a variety of experimental models. The aim of our study is to
      demonstrate the potential role of PBISe in the treatment of HCC. The anti
      proliferative and pro-apoptotic ability of PBISe is studied in vitro in four
      human HCC cell lines and in vivo in a spontaneous murine HCC model. Inhibition of
      cancer growth was performed by cell viability assay and apoptosis by caspase 3/7,
      PARP cleavage, annexin-V, and TUNEL assays. Role of PBISe on PI3 kinase, MAPK and
      STAT3 signaling is determined by Western blotting. In vivo effects of PBISe on
      tumor sizes were monitored using MRI in a spontaneous murine HCC. Liver tissues
      from the PBISe-treated mice are analyzed for angiogenesis, proliferation, and
      signaling pathway markers. Overall, PBISe activated caspase-3/7 and increased DNA
      fragmentation, which is positively correlated with the increased PARP cleavage.
      PBISe promoted apoptosis by inhibiting PI3K, MAPK, and STAT3 signaling with
      significant reduction in the tumor sizes (p < 0.007). PBISe-treated tumors
      reduced survival marker PCNA, and angiogenesis markers Vegf-A, Vegf-R3 and CD34.
      These results demonstrate the chemotherapeutic effects of PBISe, by inhibiting
      tumor growth and facilitating tumor apoptosis for HCC treatment. 

PMID- 27023567
TI  - Contemporary Strategies for the Synthesis of Tetrahydropyran Derivatives:
      Application to Total Synthesis of Neopeltolide, a Marine Macrolide Natural
      Product.
AB  - Tetrahydropyrans are structural motifs that are abundantly present in a range of
      biologically important marine natural products. As such, significant efforts have
      been paid to the development of efficient and versatile methods for the synthesis
      of tetrahydropyran derivatives. Neopeltolide, a potent antiproliferative marine
      natural product, has been an attractive target compound for synthetic chemists
      because of its complex structure comprised of a 14-membered macrolactone embedded
      with a tetrahydropyran ring, and twenty total and formal syntheses of this
      natural product have been reported so far. This review summarizes the total and
      formal syntheses of neopeltolide and its analogues, highlighting the synthetic
      strategies exploited for constructing the tetrahydropyran ring. 

PMID- 27023568
TI  - Lipid Production from Nannochloropsis.
AB  - Microalgae are sunlight-driven green cell factories for the production of
      potential bioactive products and biofuels. Nannochloropsis represents a genus of
      marine microalgae with high photosynthetic efficiency and can convert carbon
      dioxide to storage lipids mainly in the form of triacylglycerols and to the omega
      3 long-chain polyunsaturated fatty acid eicosapentaenoic acid (EPA). Recently,
      Nannochloropsis has received ever-increasing interests of both research and
      public communities. This review aims to provide an overview of biology and
      biotechnological potential of Nannochloropsis, with the emphasis on lipid
      production. The path forward for the further exploration of Nannochloropsis for
      lipid production with respect to both challenges and opportunities is also
      discussed. 

PMID- 27023569
TI  - Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive
      Impairments in Mice and Inhibits Acetylcholinesterase in Vitro.
AB  - Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been
      shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic
      effects. In this study, we report for the first time that fucoxanthin effectively
      protects against scopolamine-induced cognitive impairments in mice. In addition,
      fucoxanthin significantly reversed the scopolamine-induced increase of
      acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase
      activity and brain-derived neurotrophic factor (BDNF) expression. Using an in
      vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE
      with an IC50 value of 81.2 MUM. Molecular docking analysis suggests that
      fucoxanthin likely interacts with the peripheral anionic site within AChE, which
      is in accordance with enzymatic activity results showing that fucoxanthin
      inhibits AChE in a non-competitive manner. Based on our current findings, we
      anticipate that fucoxanthin might exhibit great therapeutic efficacy for the
      treatment of Alzheimer's disease by acting on multiple targets, including
      inhibiting AChE and increasing BDNF expression. 

PMID- 27023570
TI  - The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon
      Worm Lineus longissimus-Just a False Positive?
AB  - We test previous claims that the bacteria Vibrio alginolyticus produces
      tetrodotoxin (TTX) when living in symbiosis with the nemertean Lineus longissimus
      by a setup with bacteria cultivation for TTX production. Toxicity experiments on
      the shore crab, Carcinus maenas, demonstrated the presence of a paralytic toxin,
      but evidence from LC-MS and electrophysiological measurements of voltage-gated
      sodium channel-dependent nerve conductance in male Wistar rat tissue showed
      conclusively that this effect did not originate from TTX. However, a compound of
      similar molecular weight was found, albeit apparently non-toxic, and with
      different LC retention time and MS/MS fragmentation pattern than those of TTX. We
      conclude that C. maenas paralysis and death likely emanate from a compound <5
      kDa, and via a different mechanism of action than that of TTX. The similarity in
      mass between TTX and the Vibrio-produced low-molecular-weight, non-toxic compound
      invokes that thorough analysis is required when assessing TTX production. Based
      on our findings, we suggest that re-examination of some published claims of TTX
      production may be warranted. 

PMID- 27023572
TI  - Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors.
AB  - The two main components of the stress system are the hypothalamic-pituitary
      adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has
      been commonly used as a biomarker of HPA functioning, much less attention has
      been paid to the role of the SAM in this context. Studies have shown that long
      term breast cancer survivors display abnormal reactive cortisol patterns,
      suggesting a dysregulation of their HPA axis. To fully understand the integrity
      of the stress response in this population, this paper explored the diurnal and
      acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no
      history of cancer. Results revealed that breast cancer survivors displayed
      identical but elevated patterns of alpha-amylase concentrations in both diurnal
      and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p <
      0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the
      curve for the diurnal and reactive profiles was 631.54 +/- 66.94 SEM and 1238.78
      +/- 111.84 SEM, respectively. This is in sharp contrast to their cortisol
      results, which showed normal diurnal and blunted acute patterns. The complexity
      of the stress system necessitates further investigation to understand the
      synergistic relationship of the HPA and SAM axes. 

PMID- 27023573
TI  - Using a Hybrid Model to Forecast the Prevalence of Schistosomiasis in Humans.
AB  - BACKGROUND: We previously proposed a hybrid model combining both the
      autoregressive integrated moving average (ARIMA) and the nonlinear autoregressive
      neural network (NARNN) models in forecasting schistosomiasis. Our purpose in the
      current study was to forecast the annual prevalence of human schistosomiasis in
      Yangxin County, using our ARIMA-NARNN model, thereby further certifying the
      reliability of our hybrid model. METHODS: We used the ARIMA, NARNN and ARIMA
      NARNN models to fit and forecast the annual prevalence of schistosomiasis. The
      modeling time range included was the annual prevalence from 1956 to 2008 while
      the testing time range included was from 2009 to 2012. The mean square error
      (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were
      used to measure the model performance. We reconstructed the hybrid model to
      forecast the annual prevalence from 2013 to 2016. RESULTS: The modeling and
      testing errors generated by the ARIMA-NARNN model were lower than those obtained
      from either the single ARIMA or NARNN models. The predicted annual prevalence
      from 2013 to 2016 demonstrated an initial decreasing trend, followed by an
      increase. CONCLUSIONS: The ARIMA-NARNN model can be well applied to analyze
      surveillance data for early warning systems for the control and elimination of
      schistosomiasis.

PMID- 27023571
TI  - Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity
      and Selected Biological Activities.
AB  - Anthraquinones and their derivatives constitute a large group of quinoid
      compounds with about 700 molecules described. They are widespread in fungi and
      their chemical diversity and biological activities recently attracted attention
      of industries in such fields as pharmaceuticals, clothes dyeing, and food
      colorants. Their positive and/or negative effect(s) due to the 9,10
      anthracenedione structure and its substituents are still not clearly understood
      and their potential roles or effects on human health are today strongly discussed
      among scientists. As marine microorganisms recently appeared as producers of an
      astonishing variety of structurally unique secondary metabolites, they may
      represent a promising resource for identifying new candidates for therapeutic
      drugs or daily additives. Within this review, we investigate the present
      knowledge about the anthraquinones and derivatives listed to date from marine
      derived filamentous fungi's productions. This overview highlights the molecules
      which have been identified in microorganisms for the first time. The structures
      and colors of the anthraquinoid compounds come along with the known roles of some
      molecules in the life of the organisms. Some specific biological activities are
      also described. This may help to open doors towards innovative natural
      substances. 

PMID- 27023575
TI  - Exploring an Ecologically Sustainable Scheme for Landscape Restoration of
      Abandoned Mine Land: Scenario-Based Simulation Integrated Linear Programming and
      CLUE-S Model.
AB  - Understanding abandoned mine land (AML) changes during land reclamation is
      crucial for reusing damaged land resources and formulating sound ecological
      restoration policies. This study combines the linear programming (LP) model and
      the CLUE-S model to simulate land-use dynamics in the Mentougou District
      (Beijing, China) from 2007 to 2020 under three reclamation scenarios, that is,
      the planning scenario based on the general land-use plan in study area (scenario
      1), maximal comprehensive benefits (scenario 2), and maximal ecosystem service
      value (scenario 3). Nine landscape-scale graph metrics were then selected to
      describe the landscape characteristics. The results show that the coupled model
      presented can simulate the dynamics of AML effectively and the spatially explicit
      transformations of AML were different. New cultivated land dominates in scenario
      1, while construction land and forest land account for major percentages in
      scenarios 2 and 3, respectively. Scenario 3 has an advantage in most of the
      selected indices as the patches combined most closely. To conclude, reclaiming
      AML by transformation into more forest can reduce the variability and maintain
      the stability of the landscape ecological system in study area. These findings
      contribute to better mapping AML dynamics and providing policy support for the
      management of AML. 

PMID- 27023574
TI  - Heavy Physical Work: Cardiovascular Load in Male Construction Workers.
AB  - This study aimed to elucidate cardiovascular loads (CVL) in construction workers
      during work and leisure by relative heart rate (RHR) over several days.
      Furthermore, we sought to evaluate the level of CVL in relation to individual
      factors, work ability, musculoskeletal pain and subjective general health. From a
      group of 255 construction workers responding to the baseline questionnaire, the
      CVL during work and leisure time was determined by recording RHR in 42 workers
      over 3-4 days. Almost 60% of the workday was spent below 20% RHR. The mean RHR
      during work for all participants was 16% RHR, with large differences between
      professions. On average, the 42 workers spent 14% of the workday at a RHR above
      33%, and four subjects (10%) had a mean RHR above 33% during work. Eight (19%) of
      the participants had a mean length of their workday exceeding calculated maximal
      acceptable work time. Seven persons (17%) experienced on average one or more
      episode(s) of 5 min or more continuously above 33% RHR. The cardiovascular load
      at work was significantly associated with age and VO(2max), but not with work
      ability, musculoskeletal pain or subjective general health.

PMID- 27023576
TI  - Primary Paediatric Bronchial Airway Epithelial Cell in Vitro Responses to
      Environmental Exposures.
AB  - The bronchial airway epithelial cell (BAEC) is the site for initial encounters
      between inhaled environmental factors and the lower respiratory system. Our
      hypothesis was that release of pro inflammatory interleukins (IL)-6 and IL-8 from
      primary BAEC cultured from children will be increased after in vitro exposure to
      common environmental factors. Primary BAEC were obtained from children undergoing
      clinically indicated routine general anaesthetic procedures. Cells were exposed
      to three different concentrations of lipopolysaccharide (LPS) or house dust mite
      allergen (HDM) or particulates extracted from side stream cigarette smoke (SSCS).
      BAEC were obtained from 24 children (mean age 7.0 years) and exposed to stimuli.
      Compared with the negative control, there was an increase in IL-6 and IL-8
      release after exposure to HDM (p <= 0.001 for both comparisons). There was
      reduced IL-6 after higher compared to lower SSCS exposure (p = 0.023). There was
      no change in BAEC release of IL-6 or IL-8 after LPS exposure. BAEC from children
      are able to recognise and respond in vitro with enhanced pro inflammatory
      mediator secretion to some inhaled exposures. 

PMID- 27023577
TI  - Using the Reverse Shock Index at the Injury Scene and in the Emergency Department
      to Identify High-Risk Patients: A Cross-Sectional Retrospective Study.
AB  - BACKGROUND: The ratio of systolic blood pressure (SBP) to heart rate (HR), called
      the reverse shock index (RSI), is used to evaluate the hemodynamic stability of
      trauma patients. A SBP lower than the HR (RSI < 1) indicates the probability of
      hemodynamic shock. The objective of this study was to evaluate whether the RSI as
      evaluated by emergency medical services (EMS) personnel at the injury scene (EMS
      RSI) and the physician in the emergency department (ED RSI) could be used as an
      additional variable to identify patients who are at high risk of more severe
      injury. METHODS: Data obtained from all 16,548 patients added to the trauma
      registry system at a Level I trauma center between January 2009 and December 2013
      were retrospectively reviewed. Only patients transferred by EMS were included in
      this study. A total of 3715 trauma patients were enrolled and subsequently
      divided into four groups: group I patients had an EMS RSI >=1 and an ED RSI >=1
      (n = 3485); group II an EMS RSI >= 1 and an ED RSI < 1 (n = 85); group III an EMS
      RSI < 1 and an ED RSI >= 1 (n = 98); and group IV an EMS RSI < 1 and a ED RSI < 1
      (n = 47). A Pearson's chi2 test, Fisher's exact test, or independent Student's t
      test was conducted to compare trauma patients in groups II, III, and IV with
      those in group I. RESULTS: Group II and IV patients had a higher injury severity
      score, a higher incidence of commonly associated injuries, and underwent more
      procedures (including intubation, chest tube insertion, and blood transfusion in
      the ED) than patients in group I. Group II and IV patients were also more likely
      to receive a severe injury to the thoracoabdominal area. These patients also had
      worse outcomes regarding the length of stay in hospital and intensive care unit
      (ICU), the proportion of patients admitted to ICU, and in-hospital mortality.
      Group II patients had a higher adjusted odds ratio for mortality (5.8-times
      greater) than group I patients. CONCLUSIONS: Using an RSI < 1 as a threshold to
      evaluate the hemodynamic condition of the patients at the injury scene and upon
      arrival to the ED provides valid information regarding deteriorating outcomes for
      certain subgroups of patients in the ED setting. Particular attention and
      additional resources should be provided to patients with an EMS RSI >= 1 that
      deteriorates to an RSI < 1 upon arrival to the ED since a higher odds of
      mortality was found in these patients.

PMID- 27023578
TI  - Children's Blood Lead Seasonality in Flint, Michigan (USA), and Soil-Sourced Lead
      Hazard Risks.
AB  - In Flint; MI; USA; a public health crisis resulted from the switching of the
      water supply from Lake Huron to a more corrosive source from the Flint River in
      April 2014; which caused lead to leach from water lines. Between 2010 and 2015;
      Flint area children's average blood lead patterns display consistent peaks in the
      third quarter of the year. The third quarter blood lead peaks displayed a
      declining trend between 2010 and 2013; then rose abruptly between the third
      quarters of 2013 from 3.6% blood lead levels >=5 ug/dL to a peak of about 7% in
      the third quarter of 2014; an increase of approximately 50%. The percentage of
      blood lead level >=5 ug/dL in the first quarter of 2015 then dropped to 2.3%;
      which was the same percentage as the first quarter of 2014 (prior to the Flint
      River water source change). The Flint quarterly blood lead level peak then rose
      to about 6% blood lead levels >= 5 ug/dL in the third quarter of 2015; and then
      declined to about 2.5% in the fourth quarter of 2015. Soil lead data collected by
      Edible Flint food collaborative reveal generally higher soil lead values in the
      metropolitan center for Flint; with lower values in the outskirts of the city.
      The questions that are not being asked is why did children's blood lead levels
      display a seasonal blood lead pattern before the introduction of the new water
      supply in Flint; and what are the implications of these seasonal blood lead
      patterns? Based upon previous findings in Detroit and other North American cities
      we infer that resuspension to the air of lead in the form of dust from lead
      contaminated soils in Flint appears to be a persistent contribution to lead
      exposure of Flint children even before the change in the water supply from Lake
      Huron to the Flint River. 

PMID- 27023579
TI  - Influence of Occupational and Environmental Exposure to Low Concentrations of
      Polychlorobiphenyls and a Smoking Habit on the Urinary Excretion of
      Corticosteroid Hormones.
AB  - The effects of occupational exposure to low concentrations of polychlorobiphenyls
      (PCBs) on the urinary excretion of corticosteroid hormones were evaluated, taking
      into account the influence of cigarette smoking. The study included 26 males
      working as electrical maintenance staff in a steel factory, previously exposed to
      a mixture of PCBs (exposed workers), and 30 male workers with no occupational
      exposure to PCBs (controls). Serum PCBs (33 congeners), urinary 17
      hydroxycorticosteroids, 17-ketosteroids (KS) and pregnanes, and their respective
      glucuronidated and sulfonated compounds, were determined for each subject. PCBs
      were significantly higher in the exposed workers than controls, and were
      correlated with age. Both the urinary concentrations of the total 17-KS and
      pregnanes, and those of some single steroids and their glucuronidated compounds,
      were significantly lower in the exposed workers than controls, but higher in
      smokers than the non-smokers + ex-smokers. Two-way analysis of variance showed a
      negative association between serum PCBs and both total glucuronidated 17-KS and
      total and glucuronidated pregnanes, and a positive association between cigarette
      smoking and both total and glucuronidated 17-KS. PCBs seem to act as endocrine
      disruptors by reducing the urinary excretion of corticosteroid hormones,
      particularly of the glucuronidated fraction. Cigarette smoking could boost these
      effects of PCBs in smokers. 

PMID- 27023580
TI  - Influences of Green Outdoors versus Indoors Environmental Settings on
      Psychological and Social Outcomes of Controlled Exercise.
AB  - This study addressed a methodological gap by comparing psychological and social
      outcomes of exercise in green outdoors versus built indoors settings, whilst
      rigorously controlling exercise mode and intensity. The hypotheses were that
      greater improvements or more desirable values for directed attention, mood,
      perceived exertion, social interaction time, intention for future exercise
      behaviour and enjoyment would be associated with outdoors compared to indoors
      exercise. Following a baseline session, paired participants completed two
      conditions of 15 min of cycling on an ergometer placed outside in a natural
      environment and inside in a laboratory setting in a randomized, counter-balanced
      order. At pre- and post-exercise, directed attention was measured with the digit
      span backwards task, and mood was assessed with the Profile of Mood States.
      During the exercise session, visual and verbal interactions were recorded by
      means of experimenter observations. After each exercise session, participants
      provided self-reports of their enjoyment of the exercise, perceived exertion and
      intention for future exercise in the same environment. Social interaction time
      was significantly greater during outdoors exercise versus indoors; on average,
      participants engaged in three minutes more social interaction during exercise
      outdoors compared to indoors. Social interaction time significantly predicted
      intention for future exercise in the outdoors condition, but did not in the
      indoor condition. There was a significant time by condition interaction for
      directed attention. Scores worsened in the indoors condition, but improved in the
      outdoors condition. There was no statistically-significant time by condition
      interaction for mood and no significant difference between conditions for either
      perceived exertion or intention. Taken together, these findings show that
      exercise in a natural environment may promote directed attention and social
      interactions, which may positively influence future exercise intentions. 

PMID- 27023581
TI  - Risk Assessment of Arsenic in Rice Cereal and Other Dietary Sources for Infants
      and Toddlers in the U.S.
AB  - Currently, there are no set standards or quantitative guidelines available in the
      U.S. for arsenic levels in rice cereal, one of the most common first solid foods
      for infants. The objective of this study was to evaluate whether the detected
      levels of inorganic arsenic (As(i)) in rice cereal in the U.S. market are safe
      for consumption by infants and toddlers. A risk assessment was conducted based on
      literature reviews of the reported As(i) in rice cereal from the U.S. Food and
      Drug Administration's (FDA) survey and the recommended daily intake of rice
      cereal by body weight, for infants and toddlers between four and 24 months old.
      As a part of risk management, a maximum contaminant level (MCL) for Asi in rice
      cereal was computed considering overall exposure sources including drinking
      water, infant formula, and other infant solid foods. Hazard quotients (HQs) for
      acute and chronic exposures were calculated based on the U.S. Agency for Toxic
      Substances and Disease Registry's (ATSDR) Minimal Risk Level (MRL)(acute) (5.0 *
      10(-3) mg/kg/day) and MRL(chronic) (3.0 * 10(-4) mg/kg/day). A cancer slope or
      potency factor of 1.5 mg/kg/day was used to predict an incremental lifetime
      cancer risk (ILCR). Exposure assessment showed that the largest source of As(i)
      for infants and toddlers between four and 24 months old was rice cereal (55%),
      followed by other infant solid food (19%), and drinking water (18%). Infant
      formula was the smallest source of As(i) for babies (9%) at the 50th percentile
      based on Monte Carlo simulations. While HQ(acute) were consistently below 1.0,
      HQ(chronic) at the 50 and 75th percentiles exceeded 1.0 for both rice cereal and
      total sources. ILCR ranged from 10(-6) (50th) to 10(-5) (75th percentile). MCLs
      for As(i) in rice cereal ranged from 0.0 (chronic) to 0.4 mg/kg (acute
      exposures).

PMID- 27023582
TI  - Age- and Sex-Specific Trends in Lung Cancer Mortality over 62 Years in a Nation
      with a Low Effort in Cancer Prevention.
AB  - BACKGROUND: A decrease in lung cancer mortality among females below 50 years of
      age has been reported for countries with significant tobacco control efforts. The
      aim of this study was to describe the lung cancer deaths, including the mortality
      rates and proportions among total deaths, for females and males by age at death
      in a country with a high smoking prevalence (Germany) over a time period of 62
      years. METHODS: The vital statistics data were analyzed using a joinpoint
      regression analysis stratified by age and sex. An age-period-cohort analysis was
      used to estimate the potential effects of sex and school education on mortality.
      RESULTS: After an increase, lung cancer mortality among women aged 35-44 years
      remained stable from 1989 to 2009 and decreased by 10.8% per year from 2009 to
      2013. CONCLUSIONS: Lung cancer mortality among females aged 35-44 years has
      decreased. The potential reasons include an increase in the number of never
      smokers, following significant increases in school education since 1950,
      particularly among females.

PMID- 27023583
TI  - A Review of the Water and Energy Sectors and the Use of a Nexus Approach in Abu
      Dhabi.
AB  - Rapid population increase coupled with urbanization and industrialization has
      resulted in shortages of water in the Middle East. This situation is further
      exacerbated by global climate change due to greenhouse gas emissions. Recent
      research advocates that solutions to the global water security and scarcity
      crisis must involve water-energy nexus approaches. This means adopting policies
      and strategies that harmonize these inter-related sectors to minimize
      environmental impact while maximizing human benefit. In the case of Abu Dhabi,
      when designing and locating oil/gas refineries and associated power generation
      facilities, previous relevant decisions were based on simple economic and
      geographical grounds, such as nearness to oil rigs, pipelines, existing
      industries and port facilities, etc. The subsequent design and location of water
      abstraction and treatment works operated by the waste heat from these refining
      and/or power generation processes was catered for as an afterthought, meaning
      that there is now a mismatch between the water and energy supplies and demands.
      This review study was carried out to show how Abu Dhabi is trying now to
      integrate its water-energy sectors using a nexus approach so that future
      water/power infrastructure is designed optimally and operated in harmony,
      especially in regard to future demand. Based upon this review work, some
      recommendations are made for designers and policy makers alike to bolster the
      nexus approach that Abu Dhabi is pursuing. 

PMID- 27023584
TI  - The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is
      Mediated by Autophagic Pathways.
AB  - Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect
      intelligence development and the learning ability and memory of children.
      Therefore, necessary measures should be taken to protect the central nervous
      system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing
      glycosphingolipids that are constituents of mammalian cell membranes and are more
      abundantly expressed in the CNS. Studies have shown that gangliosides constitute
      a useful tool in the attempt to promote functional recovery of CNS and can
      reverse Pb-induced impairments of synaptic plasticity in rats. However, the
      detailed mechanisms have yet to be fully understood. In our present study, we
      tried to investigate the role of gangliosides in Pb-induced injury in hippocampus
      neurons and to further confirm the detailed mechanism. Our results show that Pb
      induced injuries in the spatial reference memory were associated with a reduction
      of cell viability and cell apoptosis, and treatment with gangliosides markedly
      ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides
      further attenuated Pb-induced the abnormal autophagic process by regulation of
      mTOR pathways. In summary, our study establishes the efficacy of gangliosides as
      neuroprotective agents and provides a strong rationale for further studies on the
      underlying mechanisms of their neuroprotective functions. 

PMID- 27023585
TI  - Association between the Hypertriglyceridemic Waist Phenotype, Prediabetes, and
      Diabetes Mellitus in Rural Chinese Population: A Cross-Sectional Study.
AB  - BACKGROUND: The objective was to evaluate the association of the
      hypertriglyceridemic waist (HTGW) phenotype with prediabetes and diabetes (DM) in
      rural Chinese population. METHODS: In a cross-sectional study, 11,579 adults
      (5361 men and 6218 women) aged 35 years or older were recruited from rural areas
      of China. Anthropometric measurements, laboratory examinations and self-reported
      information were collected by trained personnel. The HTGW phenotype was defined
      as elevated triglycerides and elevated waist circumference. We used logistic
      regression analysis to evaluate the associations of interest. RESULTS: Adults
      with the HTGW phenotype had a significantly higher prevalence of prediabetes and
      diabetes than those without the HTGW phenotype. Compared with the normal waist
      normal triglycerides (NWNT) group, those in the HTGW group had a higher adjusted
      odds ratio of diabetes (OR: 2.10; 95% CI: 1.62-2.73). The association for
      diabetes was stronger for men (OR: 2.27; 95% CI: 1.52-3.40) than for women (OR:
      1.86; 95% CI: 1.32-2.63). However, multivariate analysis indicated that the HTGW
      phenotype was not associated with prediabetes. CONCLUSIONS: This study
      demonstrated that the HTGW phenotype was associated with diabetes in a large
      rural Chinese population, and suggested this phenotype as a simple screening tool
      to identify adults with cardiometabolic conditions.

PMID- 27023586
TI  - The Injury Profile of an Australian Specialist Policing Unit.
AB  - This study investigated the injuries sustained by an Australian specialist police
      division. Injury records spanning four-years were analyzed. The role being
      performed when the injury occurred, injury cause, body part injured, and injury
      related costs were quantified. The percentage of personnel injured multiple times
      was documented. One hundred and thirty eight personnel reported injuries, 58 of
      these on multiple occasions. This resulted in 229 injuries and 76 claims being
      raised. Half of the injuries occurred during operational policing tasks, however
      training activities accounted for >30% of injuries. The most common injury was
      strain/sprain, and upper body injuries were 2.5-times more common than lower-body
      or torso injuries. 1107 shifts were lost, and injuries cost the organization
      $487,159 (Australian Dollars) over the four-year period. The injury costs (both
      financial and in manpower) may prompt policy makers to review the current
      training and post-injury rehabilitation protocols. 

PMID- 27023587
TI  - A Neurophysiological Approach for Evaluating Noise-Induced Sleep Disturbance:
      Calculating the Time Constant of the Dynamic Characteristics in the Brainstem.
AB  - Chronic sleep disturbance induced by traffic noise is considered to cause
      environmental sleep disorder, which increases the risk of cardiovascular disease,
      stroke, diabetes and other stress-related diseases. However, noise indices for
      the evaluation of sleep disturbance are not based on the neurophysiological
      process of awakening regulated by the brainstem. In this study, through the
      neurophysiological approach, we attempted (1) to investigate the thresholds of
      awakening due to external stimuli in the brainstem; (2) to evaluate the dynamic
      characteristics in the brainstem and (3) to verify the validity of existing noise
      indices. Using the mathematical Phillips-Robinson model, we obtained thresholds
      of awakening in the brainstem for different durations of external stimuli. The
      analysis revealed that the brainstem seemed insensitive to short stimuli and that
      the response to external stimuli in the brainstem could be approximated by a
      first-order lag system with a time constant of 10-100 s. These results suggest
      that the brainstem did not integrate sound energy as external stimuli, but
      neuroelectrical signals from auditory nerve. To understand the awakening risk
      accumulated in the brainstem, we introduced a new concept of "awakening
      potential" instead of sound energy. 

PMID- 27023588
TI  - A Rat alpha-Fetoprotein Binding Activity Prediction Model to Facilitate
      Assessment of the Endocrine Disruption Potential of Environmental Chemicals.
AB  - Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol
      (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with
      the endocrine system and cause adverse health effects. Huge public health concern
      about endocrine disruptors has arisen. One of the mechanisms of endocrine
      disruption is through binding of endocrine disruptors with the hormone receptors
      in the target cells. Entrance of endocrine disruptors into target cells is the
      precondition of endocrine disruption. The binding capability of a chemical with
      proteins in the blood affects its entrance into the target cells and, thus, is
      very informative for the assessment of potential endocrine disruption of
      chemicals. alpha-fetoprotein is one of the major serum proteins that binds to a
      variety of chemicals such as estrogens. To better facilitate assessment of
      endocrine disruption of environmental chemicals, we developed a model for alpha
      fetoprotein binding activity prediction using the novel pattern recognition
      method (Decision Forest) and the molecular descriptors calculated from two
      dimensional structures by Mold2 software. The predictive capability of the model
      has been evaluated through internal validation using 125 training chemicals
      (average balanced accuracy of 69%) and external validations using 22 chemicals
      (balanced accuracy of 71%). Prediction confidence analysis revealed the model
      performed much better at high prediction confidence. Our results indicate that
      the model is useful (when predictions are in high confidence) in endocrine
      disruption risk assessment of environmental chemicals though improvement by
      increasing number of training chemicals is needed. 

PMID- 27023589
TI  - Association between Atmospheric Fine Particulate Matter and Hospital Admissions
      for Chronic Obstructive Pulmonary Disease in Southwestern Taiwan: A Population
      Based Study.
AB  - OBJECTIVES: This paper reports on the findings of a population-based study to
      evaluate the relationship between atmospheric fine particulate matter (PM2.5)
      levels and hospital admissions for chronic obstructive pulmonary disease (COPD)
      in southwestern Taiwan over a three-year period, 2008-2010. METHODS: Data on
      hospital admissions for COPD and PM2.5 levels were obtained from the National
      Health Insurance Research database (NHIRD) and the Environmental Protection
      Administration from 2008 to 2010, respectively. The lag structure of relative
      risks (RRs) of hospital admissions for COPD was estimated using a Poisson
      regression model. RESULTS: During the study period, the overall average
      hospitalization rate of COPD and mean 24-h average level of PM2.5 was 0.18% and
      39.37 MUg/m3, respectively. There were seasonal variations in PM2.5
      concentrations in southwestern Taiwan, with higher PM2.5 concentrations in both
      spring (average: 48.54 MUg/m3) and winter (49.96 MUg/m3) than in summer (25.89
      MUg/m3) and autumn (33.37 MUg/m3). Increased COPD admissions were significantly
      associated with PM2.5 in both spring (February-April) and winter (October
      January), with the relative risks (RRs) for every 10 MUg/m3 increase in PM2.5
      being 1.25 (95% CI = 1.22-1.27) and 1.24 (95% CI = 1.23-1.26), respectively, at a
      lag zero days (i.e., no lag days). Lag effects on COPD admissions were observed
      for PM2.5, with the elevated RRs beginning at lag zero days and larger RRs
      estimates tending to occur at longer lags (up to six days, i.e., lag 0-5 days).
      CONCLUSIONS: In general, findings reveal an association between atmospheric fine
      particulate matter (PM2.5) and hospital admissions for COPD in southwestern
      Taiwan, especially during both spring and winter seasons.

PMID- 27023590
TI  - Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that
      Bind Estrogen Receptors.
AB  - Flavonoids are frequently used as dietary supplements in the absence of research
      evidence regarding health benefits or toxicity. Furthermore, ingested doses could
      far exceed those received from diet in the course of normal living. Some
      flavonoids exhibit binding to estrogen receptors (ERs) with consequential
      vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory
      authorities must consider both beneficial claims and potential adverse effects,
      warranting the increases in research that has spanned almost two decades. Here,
      we report pathway enrichment of 14 targets from the Comparative Toxicogenomics
      Database (CTD) and the Herbal Ingredients' Targets (HIT) database for 22
      flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from
      our earlier studies, and were here found in mainly involved in three types of
      biological processes, ER regulation, estrogen metabolism and synthesis, and
      apoptosis. Besides cancers, we conjecture that the flavonoids may affect several
      diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis,
      viral myocarditis and non-alcoholic fatty liver disease could be implicated. More
      generally, apoptosis processes may be importantly evolved biological functions of
      flavonoids that bind ERs and high dose ingestion of those flavonoids could
      adversely disrupt the cellular apoptosis process. 

PMID- 27023591
TI  - Identification of Haplotype Tag Single-Nucleotide Polymorphisms within the PPAR
      Family Genes and Their Clinical Relevance in Patients with Major Trauma.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) play important
      roles in the development of inflammatory diseases and sepsis. Recently, genetic
      variants of PPARs genes have been widely studied in some inflammatory diseases.
      However, the association between PPAR family of genes polymorphisms and sepsis
      risk in trauma patients was little known. METHODS: SNPs were selected from the
      PPARs genes through constructing haplotype blocks and genotyped by the improved
      multiplex ligation detection reaction (iMLDR) method. The association between the
      selected SNPs and the risk of sepsis and multiple organ dysfunction (MOD) scores
      was evaluated in 734 trauma patients. In addition, tumor necrosis factor alpha
      (TNFalpha) production of peripheral blood leukocytes was also analyzed after
      lipopolysaccharide (LPS) stimulation. RESULTS: Our results revealed that there
      were significant associations between the rs10865710 polymorphism and the risk of
      sepsis and MOD scores in Chinese Han trauma patients. Further, we found that the
      level of TNFalpha production was higher in patients with the rs10865710 G allele
      compared to those with the variant C allele. CONCLUSIONS: The rs10865710
      polymorphism in the PPARgamma gene might be used to assess the risk of sepsis and
      multiple organ dysfunction syndrome (MODS) in trauma patients.

PMID- 27023592
TI  - Determinants of the Bovine Leukemia Virus Envelope Glycoproteins Involved in
      Infectivity, Replication and Pathogenesis.
AB  - Interaction of viral envelope proteins with host cell membranes has been
      extensively investigated in a number of systems. However, the biological
      relevance of these interactions in vivo has been hampered by the absence of
      adequate animal models. Reverse genetics using the bovine leukemia virus (BLV)
      genome highlighted important functional domains of the envelope protein involved
      in the viral life cycle. For example, immunoreceptor tyrosine-based activation
      motifs (ITAM) of the envelope transmembrane protein (TM) are essential
      determinants of infection. Although cell fusion directed by the aminoterminal end
      of TM is postulated to be essential, some proviruses expressing fusion-deficient
      envelope proteins unexpectedly replicate at wild-type levels. Surprisingly also,
      a conserved N-linked glycosylation site of the extracellular envelope protein
      (SU) inhibits cell-to-cell transmission suggesting that infectious potential has
      been limited during evolution. In this review, we summarize the knowledge
      pertaining to the BLV envelope protein in the context of viral infection,
      replication and pathogenesis. 

PMID- 27023593
TI  - Frequency of Natural Resistance within NS5a Replication Complex Domain in
      Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance
      Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment.
AB  - Different HCV subtypes may naturally harbor different resistance selection to
      anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database
      were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a
      resistance-associated polymorphisms (RAPs) were more frequently detected in HCV
      G1b compared to G1a. The prevalence of polymorphisms associated with cross
      resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV,
      ombitasvir, and OMV) or scheduled to come into clinical use in the near future
      (IDX719, elbasvir, and ELV) was higher in G1b compared to G1a (37/1552 (2.4%) in
      1b sequences and 15/1209 (1.2%) in 1a isolates, p = 0.040). Interestingly, on the
      basis of the genotype-specific resistance pattern, 95 (6.1%) G1b sequences had
      L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5%) harbored L31M RAP,
      conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001). Finally, 28 (2.3%) G1a
      and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001). In conclusion,
      the pattern of subtype-specific resistance selection in the naturally occurring
      strains may guide the treatment option in association with direct acting
      antivirals (DAAs) targeting different regions, particularly in patients that are
      difficult to cure, such as those with advanced liver disease or individuals who
      have failed previous DAAs. 

PMID- 27023594
TI  - Fructose Containing Sugars at Normal Levels of Consumption Do Not Effect
      Adversely Components of the Metabolic Syndrome and Risk Factors for
      Cardiovascular Disease.
AB  - The objective of the current study was to explore our hypothesis that average
      consumption of fructose and fructose containing sugars would not increase risk
      factors for cardiovascular disease (CVD) and the metabolic syndrome (MetS). A
      randomized, double blind, parallel group study was conducted where 267
      individuals with BMI between 23 and 35 kg/m2 consumed low fat sugar sweetened
      milk, daily for ten weeks as part of usual weight-maintenance diet. One group
      consumed 18% of calories from high fructose corn syrup (HFCS), another group
      consumed 18% of calories from sucrose, a third group consumed 9% of calories from
      fructose, and the fourth group consumed 9% of calories from glucose. There was a
      small change in waist circumference (80.9 +/- 9.5 vs. 81.5 +/- 9.5 cm) in the
      entire cohort, as well as in total cholesterol (4.6 +/- 1.0 vs. 4.7 +/- 1.0
      mmol/L, p < 0.01), triglycerides (TGs) (11.5 +/- 6.4 vs. 12.6 +/- 8.9 mmol/L, p <
      0.01), and systolic (109.2 +/- 10.2 vs. 106.1 +/- 10.4 mmHg, p < 0.01) and
      diastolic blood pressure (69.8 +/- 8.7 vs. 68.1 +/- 9.7 mmHg, p < 0.01). The
      effects of commonly consumed sugars on components of the MetS and CVD risk
      factors are minimal, mixed and not clinically significant. 

PMID- 27023596
TI  - Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers:
      A Randomized, Double-Blind Placebo-Controlled Clinical Trial.
AB  - Intercontinental air travel can be stressful, especially for respiratory health.
      Elderberries have been used traditionally, and in some observational and clinical
      studies, as supportive agents against the common cold and influenza. This
      randomized, double-blind placebo-controlled clinical trial of 312 economy class
      passengers travelling from Australia to an overseas destination aimed to
      investigate if a standardised membrane filtered elderberry (Sambucus nigra L.)
      extract has beneficial effects on physical, especially respiratory, and mental
      health. Cold episodes, cold duration and symptoms were noted in a daily diary and
      assessed using the Jackson score. Participants also completed three surveys
      containing questions regarding upper respiratory symptoms (WURSS-21) and quality
      of life (SF-12) at baseline, just before travel and at 4-days after travel. Most
      cold episodes occurred in the placebo group (17 vs. 12), however the difference
      was not significant (p = 0.4). Placebo group participants had a significantly
      longer duration of cold episode days (117 vs. 57, p = 0.02) and the average
      symptom score over these days was also significantly higher (583 vs. 247, p =
      0.05). These data suggest a significant reduction of cold duration and severity
      in air travelers. More research is warranted to confirm this effect and to
      evaluate elderberry's physical and mental health benefits. 

PMID- 27023595
TI  - Protein Considerations for Optimising Skeletal Muscle Mass in Healthy Young and
      Older Adults.
AB  - Skeletal muscle is critical for human health. Protein feeding, alongside
      resistance exercise, is a potent stimulus for muscle protein synthesis (MPS) and
      is a key factor that regulates skeletal muscle mass (SMM). The main purpose of
      this narrative review was to evaluate the latest evidence for optimising the
      amino acid or protein source, dose, timing, pattern and macronutrient coingestion
      for increasing or preserving SMM in healthy young and healthy older adults. We
      used a systematic search strategy of PubMed and Web of Science to retrieve all
      articles related to this review objective. In summary, our findings support the
      notion that protein guidelines for increasing or preserving SMM are more complex
      than simply recommending a total daily amount of protein. Instead, multifactorial
      interactions between protein source, dose, timing, pattern and macronutrient
      coingestion, alongside exercise, influence the stimulation of MPS, and thus
      should be considered in the context of protein recommendations for regulating
      SMM. To conclude, on the basis of currently available scientific literature,
      protein recommendations for optimising SMM should be tailored to the population
      or context of interest, with consideration given to age and resting/post
      resistance exercise conditions. 

PMID- 27023597
TI  - Potassium and Obesity/Metabolic Syndrome: A Systematic Review and Meta-Analysis
      of the Epidemiological Evidence.
AB  - The objective of this study was to investigate the associations between potassium
      and obesity/metabolic syndrome. We identified eight relevant studies and applied
      meta-analysis, and nonlinear dose-response analysis to obtain the available
      evidence. The results of the pooled analysis and systematic review indicated that
      high potassium intake could not reduce the risk of obesity (pooled OR = 0.78; 95%
      CI: 0.61-1.01), while serum potassium and urinary sodium-to-potassium ratio was
      associated with obesity. Potassium intake was associated with metabolic syndrome
      (pooled OR = 0.75; 95% CI: 0.50-0.97). Nonlinear analysis also demonstrated a
      protective effect of adequate potassium intake on obesity and metabolic syndrome.
      Adequate intake of fruits and vegetables, which were the major sources of
      potassium, was highly recommended. However, additional pertinent studies are
      needed to examine the underlying mechanism. 

PMID- 27023598
TI  - Assessment of Nutrient Intakes: Introduction to the Special Issue.

PMID- 27023599
TI  - Gender Differences in Dietary Patterns and Their Association with the Prevalence
      of Metabolic Syndrome among Chinese: A Cross-Sectional Study.
AB  - Few studies have investigated gender differences in dietary intake. The objective
      of this cross-sectional study was to examine gender differences in dietary
      patterns and their association with the prevalence of metabolic syndrome. The
      food intakes of 3794 subjects enrolled by a two-stage cluster stratified sampling
      method were collected using a valid semi-quantitative food frequency
      questionnaire (FFQ). Metabolic syndrome (MetS) was defined according to the
      International Diabetes Federation (IDF) and its prevalence was 35.70% in the
      sample (37.67% in men and 24.67% in women). Dietary patterns were identified
      using factor analysis combined with cluster analysis and multiple group
      confirmatory factor analysis was used to assess the factorial invariance between
      gender groups. The dominating dietary pattern for men was the "balanced" dietary
      pattern (32.65%) and that for women was the "high-salt and energy" dietary
      pattern (34.42%). For men, the "animal and fried food" dietary pattern was
      related to higher risk of MetS (odds ratio: 1.27; 95% CI: 1.01-1.60), after
      adjustment for age, marital status, socioeconomic status and lifestyle factors.
      For women, the "high-salt and energy" dietary pattern was related to higher risk
      of MetS (odds ratio: 2.27; 95% CI: 1.24-4.14). We observed gender differences in
      dietary patterns and their association with the prevalence of MetS. For men, the
      "animal and fried food" dietary pattern was associated with enhancive likelihood
      of MetS. For women, it was the "high-salt and energy" dietary pattern. 

PMID- 27023600
TI  - Maternal-Fetal Cancer Risk Assessment of Ochratoxin A during Pregnancy.
AB  - Increasing evidence has demonstrated that in utero exposure to environmental
      chemicals may interfere with fetal development and increase the risk of disease
      and cancer development later in life. Ochratoxin A (OTA) has been proven to
      induce diverse toxic effects including teratogenicity, carcinogenicity,
      immunotoxicity and potential endocrine disruption. Due to the continuous and
      widespread occurrence of OTA as a potential contaminant of staple foods, there is
      increasing concern of in utero exposure of fetus to this mycotoxin. In this
      study, maternal-fetal risk assessment of OTA during pregnancy was conducted using
      the benchmark dose approach for genotoxic carcinogens. The daily intake of OTA
      for Egyptian pregnant women was estimated based on their serum OTA level using
      the refined Klaassen equation for pregnancy. Fetal exposure level was also
      estimated based on the maternal data. Comparison between the estimated daily
      exposure and the negligible cancer risk intake (NCRI), and the calculation of
      margin of exposure (MOE) implicated that OTA exposure from dietary intake would
      be of low health concern for this general subpopulation of Egyptian women. This
      subpopulation of pregnant women was generally estimated not to be in high-risk
      for toxicity induced by OTA. 

PMID- 27023601
TI  - Use of Botulinum Toxin A in the Treatment of Lower Urinary Tract Disorders: A
      Review of the Literature.
AB  - Botulinum neurotoxin (BoNT) is used to treat a variety of ailments, and its
      therapeutic application in lower urinary tract disorders (LUTDs) is well studied.
      Robust evidence supporting the efficacy and tolerability of BoNT in the treatment
      of neurogenic detrusor overactivity (NDO) and non-neurogenic overactive bladder
      (OAB) has led to regulatory approval for these conditions. Use of BoNT in the
      treatment of interstitial cystitis/bladder pain syndrome, chronic pelvic pain,
      and detrusor sphincter dyssynergia has demonstrated some promise, but is still
      evolving and off-label for these indications. Trials to date do not support the
      use of BoNT for benign prostatic hyperplasia. This comprehensive review outlines
      the mechanisms of BoNT in the treatment of LUTDs in adults and presents
      background and updated data examining the efficacy and adverse events associated
      with the use of BoNT in common urologic applications. 

PMID- 27023602
TI  - Fumonisin B1 (FB1) Induces Lamellar Separation and Alters Sphingolipid Metabolism
      of In Vitro Cultured Hoof Explants.
AB  - One of the most important hoof diseases is laminitis. Yet, the pathology of
      laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or
      exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins,
      toxic secondary metabolites of fungi, might contribute to the onset of laminitis.
      In this respect, fumonsins are of special interest since horses are regarded as
      species most susceptible to this group of mycotoxins. The aim of our study was to
      investigate the influence of fumonisin B1 (FB1) on primary isolated epidermal and
      dermal hoof cells, as well as on the lamellar tissue integrity and sphingolipid
      metabolism of hoof explants in vitro. There was no effect of FB1 at any
      concentration on dermal or epidermal cells. However, FB1 significantly reduced
      the separation force of explants after 24 h of incubation. The Sa/So ratio was
      significantly increased in supernatants of explants incubated with FB1 (2.5-10
      ug/mL) after 24 h. Observed effects on Sa/So ratio were linked to significantly
      increased sphinganine concentrations. Our study showed that FB1 impairs the
      sphingolipid metabolism of explants and reduces lamellar integrity at non
      cytotoxic concentrations. FB1 might, therefore, affect hoof health. Further in
      vitro and in vivo studies are necessary to elucidate the effects of FB1 on the
      equine hoof in more detail. 

PMID- 27023603
TI  - Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Patients with
      Frailty, Medical Comorbidities or Prior Lower Urinary Tract Surgery.
AB  - Overactive bladder (OAB) symptoms increase with age and involve several
      comorbidities. OnabotulinumtoxinA (BoNT-A) intravesical injection is a treatment
      choice for patients who are intolerant of or refractory to antimuscarinics.
      However, the increased risk of urinary tract infection and elevated post-void
      residual (PVR) volume post-treatment require resolution. Male sex, baseline PVR >
      100 mL, and comorbidities are independent risk factors of adverse events (AEs)
      such as acute urinary retention (AUR). Intravesical BoNT-A injection is safe and
      effective for OAB patients with frailty, medical comorbidities such as
      Parkinson's disease (PD), chronic cerebrovascular accidents (CVA), dementia, or
      diabetes, or a history of prior lower urinary tract surgery (prostate or
      transvaginal sling surgery). Post-treatment, 60% of frail elderly patients had a
      PVR volume > 150 mL and 11% had AUR. Although intravesical BoNT-A injection is
      safe for PD patients, CVA patients had higher strain voiding rates. Diabetic
      patients were at increased risk of large PVR urine volume and general weakness
      post-treatment. Treatment results were similar between patients with and without
      a history of prostate or transvaginal sling surgery. Possible AEs and bladder
      management strategies should be conveyed to patients before treatment. Careful
      patient selection is important, and therapeutic safety and efficacy should be
      carefully balanced. 

PMID- 27023604
TI  - Rapid Detection of Escherichia coli O157 and Shiga Toxins by Lateral Flow
      Immunoassays.
AB  - Shiga toxin-producing Escherichia coli O157:H7 (STEC) cause food-borne illness
      that may be fatal. STEC strains enumerate two types of potent Shiga toxins (Stx1
      and Stx2) that are responsible for causing diseases. It is important to detect
      the E. coli O157 and Shiga toxins in food to prevent outbreak of diseases. We
      describe the development of two multi-analyte antibody-based lateral flow
      immunoassays (LFIA); one for the detection of Stx1 and Stx2 and one for the
      detection of E. coli O157 that may be used simultaneously to detect pathogenic E.
      coli O157:H7. The LFIA strips were developed by conjugating nano colloidal gold
      particles with monoclonal antibodies against Stx1 and Stx2 and anti-lipid A
      antibodies to capture Shiga toxins and O157 antigen, respectively. Our results
      indicate that the LFIA for Stx is highly specific and detected Stx1 and Stx2
      within three hours of induction of STEC with ciprofloxacin at 37  degrees C. The
      limit of detection for E. coli O157 LFIA was found to be 105 CFU/mL in ground
      beef spiked with the pathogen. The LFIAs are rapid, accurate and easy to use and
      do not require sophisticated equipment or trained personnel. Following the assay,
      colored bands on the membrane develop for end-point detection. The LFIAs may be
      used for screening STEC in food and the environment. 

PMID- 27023605
TI  - The Tip of the Four N-Terminal alpha-Helices of Clostridium sordellii Lethal
      Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating
      Small GTPases Glucosylation.
AB  - Clostridium sordellii lethal toxin (TcsL) is a powerful virulence factor
      responsible for severe toxic shock in man and animals. TcsL belongs to the large
      clostridial glucosylating toxin (LCGT) family which inactivates small GTPases by
      glucosylation with uridine-diphosphate (UDP)-glucose as a cofactor. Notably, TcsL
      modifies Rac and Ras GTPases, leading to drastic alteration of the actin
      cytoskeleton and cell viability. TcsL enters cells via receptor-mediated
      endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat) into the
      cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)
      containing membranes and to increase the glucosylation of Rac anchored to the
      lipid membrane. We have previously reported that the N-terminal four helical
      bundle structure (1-93 domain) recognizes a broad range of lipids, but that TcsL
      cat specifically binds to PS and phosphatidic acid. Here, we show using
      mutagenesis that the PS binding site is localized on the tip of the four-helix
      bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17,
      and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3,
      between helices 3 and 4, form a pocket which accommodates L-serine. The
      functional PS-binding site is required for TcsL-cat binding to the plasma
      membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high
      enzymatic activity towards membrane-anchored Ras by about three orders of
      magnitude as compared to Ras in solution. The PS-binding site is conserved in
      LCGTs, which likely retain a common mechanism of binding to the membrane for
      their full activity towards membrane-bound GTPases. 

PMID- 27023606
TI  - Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and
      Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by
      Two Different Antivenoms.
AB  - Antivenom neutralization against cobra venoms is generally low in potency,
      presumably due to poor toxin-specific immunoreactivity. This study aimed to
      investigate the effectiveness of two elapid antivenoms to neutralize the
      principal toxins purified from the venoms of the Thai monocled cobra (Naja
      kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M).
      In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T
      long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89-6.44 mg
      toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33
      mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18
      mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited)
      Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of
      antivenom against SNTX of both species, suggesting that this is the limiting
      factor on the potency of antivenom neutralization against venoms containing SNTX.
      Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61
      2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly
      attributable to the high abundance of SNTX in sea snake venom used as immunogen
      in SSAV production. The findings indicate that improving the potency of cobra
      antivenom may be possible with a proper immunogen formulation that seeks to
      overcome the limitation on SNTX immunoreactivity. 

PMID- 27023607
TI  - Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius
      Venom by Molecular Imaging.
AB  - The venom of the Eastern coral snake Micrurus fulvius can cause respiratory
      paralysis in the bitten patient, which is attributable to beta-neurotoxins (beta
      NTx). The aim of this work was to study the biodistribution and lymphatic
      tracking by molecular imaging of the main beta-NTx of M. fulvius venom. beta-NTx
      was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA)
      and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was
      60%-78%; radiochemical purity >=92%; and stability at 48 h >= 85%. The median
      lethal dose (LD50) and PLA2 activity of bioconjugated beta-NTx decreased 3 and
      2.5 times, respectively, in comparison with native beta-NTx. The immune
      recognition by polyclonal antibodies decreased 10 times. Biodistribution of beta
      NTx-DTPA-(67)Ga in rats showed increased uptake in popliteal, lumbar nodes and
      kidneys that was not observed with (67)Ga-free. Accumulation in organs at 24 h
      was less than 1%, except for kidneys, where the average was 3.7%. The inoculation
      site works as a depot, since 10% of the initial dose of beta-NTx-DTPA-(67)Ga
      remains there for up to 48 h. This work clearly demonstrates the lymphatic system
      participation in the biodistribution of beta-NTx-DTPA-(67)Ga. Our approach could
      be applied to analyze the role of the lymphatic system in snakebite for a better
      understanding of envenoming. 

PMID- 27023608
TI  - Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and
      Understanding.
AB  - The historical development of discoveries and conceptual frames for understanding
      the hemorrhagic activity induced by viperid snake venoms and by hemorrhagic
      metalloproteinases (SVMPs) present in these venoms is reviewed. Histological and
      ultrastructural tools allowed the identification of the capillary network as the
      main site of action of SVMPs. After years of debate, biochemical developments
      demonstrated that all hemorrhagic toxins in viperid venoms are zinc-dependent
      metalloproteinases. Hemorrhagic SVMPs act by initially hydrolyzing key substrates
      at the basement membrane (BM) of capillaries. This degradation results in the
      weakening of the mechanical stability of the capillary wall, which becomes
      distended owing of the action of the hemodynamic biophysical forces operating in
      the circulation. As a consequence, the capillary wall is disrupted and
      extravasation occurs. SVMPs do not induce rapid toxicity to endothelial cells,
      and the pathological effects described in these cells in vivo result from the
      mechanical action of these hemodynamic forces. Experimental evidence suggests
      that degradation of type IV collagen, and perhaps also perlecan, is the key event
      in the onset of microvessel damage. It is necessary to study this phenomenon from
      a holistic, systemic perspective in which the action of other venom components is
      also taken into consideration. 

PMID- 27023610
TI  - NORE1A Regulates MDM2 Via beta-TrCP.
AB  - Mouse Double Minute 2 Homolog (MDM2) is a key negative regulator of the master
      tumor suppressor p53. MDM2 regulates p53 on multiple levels, including acting as
      an ubiquitin ligase for the protein, thereby promoting its degradation by the
      proteasome. MDM2 is oncogenic and is frequently found to be over-expressed in
      human tumors, suggesting its dysregulation plays an important role in human
      cancers. We have recently found that the Ras effector and RASSF (Ras Association
      Domain Family) family member RASSF5/NORE1A enhances the levels of nuclear p53. We
      have also found that NORE1A (Novel Ras Effector 1A) binds the substrate
      recognition component of the SCF-ubiquitin ligase complex beta-TrCP. Here, we now
      show that NORE1A regulates MDM2 protein levels by targeting it for ubiquitination
      by SCF-beta-TrCP. We also show the suppression of NORE1A protein levels enhances
      MDM2 protein expression. Finally, we show that MDM2 can suppress the potent
      senescence phenotype induced by NORE1A over-expression. Thus, we identify a
      mechanism by which Ras/NORE1A can modulate p53 protein levels. As MDM2 has
      several important targets in addition to p53, this finding has broad implications
      for cancer biology in tumor cells that have lost expression of NORE1A due to
      promoter methylation. 

PMID- 27023609
TI  - Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro
      Combined Toxicological Effects.
AB  - Some foods and feeds are often contaminated by numerous mycotoxins, but most
      studies have focused on the occurrence and toxicology of a single mycotoxin.
      Regulations throughout the world do not consider the combined effects of
      mycotoxins. However, several surveys have reported the natural co-occurrence of
      mycotoxins from all over the world. Most of the published data has concerned the
      major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA),
      fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON).
      Concerning cereals and derived cereal product samples, among the 127 mycotoxin
      combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA
      are the most observed. However, only a few studies specified the number of co
      occurring mycotoxins with the percentage of the co-contaminated samples, as well
      as the main combinations found. Studies of mycotoxin combination toxicity showed
      antagonist, additive or synergic effects depending on the tested species, cell
      model or mixture, and were not necessarily time- or dose-dependent. This review
      summarizes the findings on mycotoxins and their co-occurrence in various foods
      and feeds from all over the world as well as in vitro experimental data on their
      combined toxicity. 

PMID- 27023611
TI  - Differential miRNA-Expression as an Adjunctive Diagnostic Tool in Neuroendocrine
      Tumors of the Lung.
AB  - Pulmonary malignancies with neuroendocrine differentiation represent a rare
      subclass of lung carcinomas, which vary in the extent of differentiation and
      grade of biological aggressiveness. In particular, neuroendocrine tumors are
      classified into well differentiated typical and atypical carcinoids as well as
      poorly differentiated large cell neuroendocrine and small cell lung carcinomas.
      Tiny MicroRNAs have been identified as reliable classifiers in distinct cancer
      types and seem to play important roles in cellular processes like regulation of
      cell growth, differentiation and apoptosis. In the present study, two different
      microRNAs (miR-21 and miR-34a) were explored for their involvements in
      pathogenesis of subtypes and finally in differential diagnosis of pulmonary
      neuroendocrine tumors. miR-21 was upregulated in poorly differentiated
      neuroendocrine tumors (mean rank: 26.8; 28.75) as compared to carcinoids (mean
      rank: 12.33; 12.07) with a significance of 0.00033. High-expression levels of miR
      34a were associated with atypical carcinoids (p = 0.010). A close association is
      implicated between the elevated miR-21 values in high-grade and miR-34a patterns
      in low-grade atypical neuroendocrine lung carcinomas, which could potentially be
      exploited as practical supportive markers for differential lung cancer diagnosis
      in routine. However, some additional extended research and validation studies are
      needed to utilize them as routine markers or potential molecular targets for
      personalized medicine. 

PMID- 27023612
TI  - Mitochondrial Redox Signaling and Tumor Progression.
AB  - Cancer cell can reprogram their energy production by switching mitochondrial
      oxidative phosphorylation to glycolysis. However, mitochondria play multiple
      roles in cancer cells, including redox regulation, reactive oxygen species (ROS)
      generation, and apoptotic signaling. Moreover, these mitochondrial roles are
      integrated via multiple interconnected metabolic and redox sensitive pathways.
      Interestingly, mitochondrial redox proteins biphasically regulate tumor
      progression depending on cellular ROS levels. Low level of ROS functions as
      signaling messengers promoting cancer cell proliferation and cancer invasion.
      However, anti-cancer drug-initiated stress signaling could induce excessive ROS,
      which is detrimental to cancer cells. Mitochondrial redox proteins could
      scavenger basal ROS and function as "tumor suppressors" or prevent excessive ROS
      to act as "tumor promoter". Paradoxically, excessive ROS often also induce DNA
      mutations and/or promotes tumor metastasis at various stages of cancer
      progression. Targeting redox-sensitive pathways and transcriptional factors in
      the appropriate context offers great promise for cancer prevention and therapy.
      However, the therapeutics should be cancer-type and stage-dependent. 

PMID- 27023613
TI  - Regulation of the Adaptive Immune Response by the IkappaB Family Protein Bcl-3.
AB  - Bcl-3 is a member of the IkappaB family of proteins and an important regulator of
      Nuclear Factor (NF)-kappaB activity. The ability of Bcl-3 to bind and regulate
      specific NF-kappaB dimers has been studied in great depth, but its physiological
      roles in vivo are still not fully understood. It is, however, becoming clear that
      Bcl-3 is essential for the proper development, survival and activity of adaptive
      immune cells. Bcl-3 dysregulation can be observed in a number of autoimmune
      pathologies, and Bcl3-deficient animals are more susceptible to bacterial and
      parasitic infection. This review will describe our current understanding of the
      roles played by Bcl-3 in the development and regulation of the adaptive immune
      response, including lymphoid organogenesis, immune tolerance, lymphocyte function
      and dendritic cell biology. 

PMID- 27023614
TI  - De Novo Transcriptome Sequencing of Desert Herbaceous Achnatherum splendens
      (Achnatherum) Seedlings and Identification of Salt Tolerance Genes.
AB  - Achnatherum splendens is an important forage herb in Northwestern China. It has a
      high tolerance to salinity and is, thus, considered one of the most important
      constructive plants in saline and alkaline areas of land in Northwest China.
      However, the mechanisms of salt stress tolerance in A. splendens remain unknown.
      Next-generation sequencing (NGS) technologies can be used for global gene
      expression profiling. In this study, we examined sequence and transcript
      abundance data for the root/leaf transcriptome of A. splendens obtained using an
      Illumina HiSeq 2500. Over 35 million clean reads were obtained from the leaf and
      root libraries. All of the RNA sequencing (RNA-seq) reads were assembled de novo
      into a total of 126,235 unigenes and 36,511 coding DNA sequences (CDS). We
      further identified 1663 differentially-expressed genes (DEGs) between the salt
      stress treatment and control. Functional annotation of the DEGs by gene ontology
      (GO), using Arabidopsis and rice as references, revealed enrichment of salt
      stress-related GO categories, including "oxidation reduction", "transcription
      factor activity", and "ion channel transporter". Thus, this global transcriptome
      analysis of A. splendens has provided an important genetic resource for the study
      of salt tolerance in this halophyte. The identified sequences and their putative
      functional data will facilitate future investigations of the tolerance of
      Achnatherum species to various types of abiotic stress. 

PMID- 27023615
TI  - tRNA Core Hypothesis for the Transition from the RNA World to the
      Ribonucleoprotein World.
AB  - Herein we present the tRNA core hypothesis, which emphasizes the central role of
      tRNAs molecules in the origin and evolution of fundamental biological processes.
      tRNAs gave origin to the first genes (mRNA) and the peptidyl transferase center
      (rRNA), proto-tRNAs were at the core of a proto-translation system, and the
      anticodon and operational codes then arose in tRNAs molecules. Metabolic pathways
      emerged from evolutionary pressures of the decoding systems. The transitions from
      the RNA world to the ribonucleoprotein world to modern biological systems were
      driven by three kinds of tRNAs transitions, to wit, tRNAs leading to both mRNA
      and rRNA. 

PMID- 27023616
TI  - Multiple Layers of Stress-Induced Regulation in tRNA Biology.
AB  - tRNAs are the fundamental components of the translation machinery as they deliver
      amino acids to the ribosomes during protein synthesis. Beyond their essential
      function in translation, tRNAs also function in regulating gene expression,
      modulating apoptosis and several other biological processes. There are multiple
      layers of regulatory mechanisms in each step of tRNA biogenesis. For example,
      tRNA 3' trailer processing is altered upon nutrient stress; tRNA modification is
      reprogrammed under various stresses; nuclear accumulation of tRNAs occurs upon
      nutrient deprivation; tRNA halves accumulate upon oxidative stress. Here we
      address how environmental stresses can affect nearly every step of tRNA biology
      and we describe the possible regulatory mechanisms that influence the function or
      expression of tRNAs under stress conditions. 

PMID- 27023618
TI  - Comparative Studies on the Stenogamous and Eurygamous Behavior of Eight Anopheles
      Species of the Hyrcanus Group (Diptera: Culicidae) in Thailand.
AB  - Establishment of laboratory colony is essential for mosquito-borne-disease
      research. Mating behavior of stenogamous Anopheles peditaeniatus and seven
      eurygamous species (Anopheles argyropus, Anopheles crawfordi, Anopheles
      nigerrimus, Anopheles nitidus, Anopheles paraliae (=An. lesteri), Anopheles
      pursati and Anopheles sinensis), were investigated and compared in this study.
      The self-mating success of adult mosquitoes in different size cages at two
      density resting surface (DRS) values, 3.6 and 7.2, was statistically significant
      between stenogamous and eurygamous species. The results obtained from comparative
      measurements of specific characters in adult females (maxillary palpomere and
      antennal sensilla characters) and males (wing and genitalia) indicate those
      characters might influence the mating success of An. peditaeniatus in a small
      cage. The gonostylus of An. peditaeniatus was shorter than the eurygamous
      species. Additionally, the lower frequency of clasper movement and shorter mating
      time could be important mechanisms that control the stenogamous behavior of An.
      peditaeniatus. Interestingly, for the first time, a cluster of large sensilla
      coeloconica was recorded on the antenna of An. argyropus and An. peditaeniatus
      females. There was no statistically significant difference in the mean number per
      female of those large antennal sensilla coeloconica among six of the eurygamous
      species. 

PMID- 27023617
TI  - Personal Genome Sequencing in Ostensibly Healthy Individuals and the PeopleSeq
      Consortium.
AB  - Thousands of ostensibly healthy individuals have had their exome or genome
      sequenced, but a much smaller number of these individuals have received any
      personal genomic results from that sequencing. We term those projects in which
      ostensibly healthy participants can receive sequencing-derived genetic findings
      and may also have access to their genomic data as participatory predispositional
      personal genome sequencing (PPGS). Here we are focused on genome sequencing
      applied in a pre-symptomatic context and so define PPGS to exclude diagnostic
      genome sequencing intended to identify the molecular cause of suspected or
      diagnosed genetic disease. In this report we describe the design of completed and
      underway PPGS projects, briefly summarize the results reported to date and
      introduce the PeopleSeq Consortium, a newly formed collaboration of PPGS projects
      designed to collect much-needed longitudinal outcome data. 

PMID- 27023620
TI  - Failure Mechanisms of Hollow Fiber Supported Ionic Liquid Membranes.
AB  - Hollow fiber supported ionic liquid membranes (SILMs) were tested using the
      bubble point method to investigate potential failure modes, including the maximum
      transmembrane pressure before loss of the ionic liquid from the support. Porous
      hollow fiber supports were fabricated with different pore morphologies using
      Matrimid((r)) and Torlon((r)) as the polymeric material and 1-hexyl-3
      methylimidalzolium bis(trifluoromethylsulfonyl)imide ([C6mim][Tf2N]) as the ionic
      liquid (IL) component. Hollow fiber SILMs were tested for their maximum pressure
      before failure, with pressure applied either from the bore side or shell side. It
      was found that the membranes exhibited one or more of three different modes of
      failure when pressurized: liquid loss (occurring at the bubble point), rupture,
      and collapse. 

PMID- 27023619
TI  - Penile Injuries in Wild and Domestic Pigs.
AB  - In boars, sexually motivated mounting can not only cause problems such as
      lameness, but penile injuries are also reported. The relevance of penis biting in
      boars is discussed controversially, but reliable data is missing. In the present
      study, boars ( n = 435) and barrows ( n = 85) from experimental farms were
      therefore evaluated for scars, fresh wounds and severe injuries of the penis.
      Similarly, 321 boars from 11 farms specializing in pork production with boars,
      and 15 sexually mature wild boars from the hunting season of 2015/16 were
      included in the study. In domestic boars, a high incidence of penile injuries was
      obvious (76.6%-87.0% of animals with scars and/or wounds at experimental farms,
      64.0%-94.9% at commercial farms). The number of boars with severe injuries was in
      a similar range in both groups (7.3% vs. 9.3%). At commercial farms, the number
      of scars but not that of fresh wounds increased per animal with age by 0.3 per
      week. Moreover, raising boars in mixed groups led to about a 1.5 times higher
      number of scars than in single-sex groups. In wild boars, a considerable
      proportion of animals (40%) revealed penile injuries, which were even severe in
      three animals. We therefore conclude that penis biting is a highly relevant and
      severe welfare problem in the male pig population, but this phenomenon is not
      limited to intensive production systems. 

PMID- 27023621
TI  - Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?
AB  - The role of omega3 alpha linolenic acid (ALA) in the maternal diet during
      pregnancy and lactation, and its effect on the prevention of disease and
      programming of health in offspring, is largely unknown. Compared to ALA, omega3
      docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely
      researched due to their direct implication in fetal neural development. In this
      literature search we found that ALA, the essential omega3 fatty acid and
      metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In
      light of new and evolving findings, this review proposes that ALA may have an
      intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal
      development as a regulator of gene programming for the prevention of metabolic
      disease and promotion of health in offspring. 

PMID- 27023622
TI  - Osteopontin-A Master Regulator of Epithelial-Mesenchymal Transition.
AB  - Osteopontin (OPN) plays an important functional role in both physiologic and
      pathologic states. OPN is implicated in the progression of fibrosis, cancer, and
      metastatic disease in several organ systems. The epithelial-mesenchymal
      transition (EMT), first described in embryology, is increasingly being recognized
      as a significant contributor to fibrotic phenotypes and tumor progression.
      Several well-established transcription factors regulate EMT and are conserved
      across tissue types and organ systems, including TWIST, zinc finger E-box-binding
      homeobox (ZEB), and SNAIL-family members. Recent literature points to an
      important relationship between OPN and EMT, implicating OPN as a key regulatory
      component of EMT programs. In this review, OPN's interplay with traditional EMT
      activators, both directly and indirectly, will be discussed. Also, OPN's ability
      to restructure the tissue and tumor microenvironment to indirectly modify EMT
      will be reviewed. Together, these diverse pathways demonstrate that OPN is able
      to modulate EMT and provide new targets for directing therapeutics. 

PMID- 27023623
TI  - Glass Polyalkenoate Cements Designed for Cranioplasty Applications: An Evaluation
      of Their Physical and Mechanical Properties.
AB  - Glass polyalkenoate cements (GPCs) have potential for skeletal cementation.
      Unfortunately, commercial GPCs all contain, and subsequently release, aluminum
      ions, which have been implicated in degenerative brain disease. The purpose of
      this research was to create a series of aluminum-free GPCs constructed from
      silicate (SiO2), calcium (CaO), zinc (ZnO) and sodium (Na2O)-containing glasses
      mixed with poly-acrylic acid (PAA) and to evaluate the potential of these cements
      for cranioplasty applications. Three glasses were formulated based on the SiO2
      CaO-ZnO-Na2O parent glass (KBT01) with 0.03 mol % (KBT02) and 0.06 mol % (KBT03)
      germanium (GeO2) substituted for ZnO. Each glass was then mixed with 50 wt % of a
      patented SiO2-CaO-ZnO-strontium (SrO) glass composition and the resultant
      mixtures were subsequently reacted with aqueous PAA (50 wt % addition) to produce
      three GPCs. The incorporation of Ge in the glass phase was found to result in
      decreased working (142 s to 112 s) and setting (807 s to 448 s) times for the
      cements manufactured from them, likely due to the increase in crosslink formation
      between the Ge-containing glasses and the PAA. Compressive (sigmac) and biaxial
      flexural (sigmaf) strengths of the cements were examined at 1, 7 and 30 days post
      mixing and were found to increase with both maturation and Ge content. The
      bonding strength of a titanium cylinder (Ti) attached to bone by the cements
      increased from 0.2 MPa, when placed, to 0.6 MPa, after 14 days maturation. The
      results of this research indicate that Germano-Silicate based GPCs have suitable
      handling and mechanical properties for cranioplasty fixation. 

PMID- 27023626
TI  - Reconstruction of the pelvic floor with Hem-o-lok clips in laparoscopic
      abdominoperineal excision of rectal cancer.

PMID- 27023625
TI  - Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer.
AB  - OBJECTIVES: MAP4K5 plays an important role in regulating a range of cellular
      responses and is involved in Wnt signaling in hematopoietic cells. However, its
      functions in human malignancies have not been studied. The major objectives of
      this study are to examine the expression, functions and clinical significance of
      MAP4K5 in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: The
      expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2)
      were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic
      pancreas samples from our institution. The RNA sequencing data of 112 PDAC
      patients were downloaded from the TCGA data portal. Immunoblotting and RNA
      sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin
      in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on
      the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1
      and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics.
      RESULTS: MAP4K5 protein is expressed at high levels specifically in the
      pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased
      or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of
      E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient
      populations. The expression levels of MAP4K5 mRNA directly correlated with the
      expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of
      112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar
      correlations between the expression of MAP4K5 and E-cadherin were observed both
      at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown
      MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5
      low correlated significantly with reduced overall survival and was an independent
      prognosticator in patients with stage II PDAC. CONCLUSIONS: MAP4K5 expression is
      decreased or lost in majority of PDACs. The strong associations between low
      MAP4K5 expression and loss of E-cadherin, reduced CES2 expression and decreased
      overall survival may suggest an important role of MAP4K5 in epithelial-to
      mesenchymal transition, chemotherapy resistance and tumor progression in
      pancreatic cancer. Targeting impaired MAP4K5 signaling may represent a new
      therapeutic strategy for pancreatic cancer.

PMID- 27023627
TI  - Changing colorectal cancer trends in Asians.

PMID- 27023624
TI  - Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis
      in Normal and Hyperammonemic Brain.
AB  - Glutamate is present in the brain at an average concentration-typically 10-12 mM
      far in excess of those of other amino acids. In glutamate-containing vesicles in
      the brain, the concentration of glutamate may even exceed 100 mM. Yet because
      glutamate is a major excitatory neurotransmitter, the concentration of this amino
      acid in the cerebral extracellular fluid must be kept low-typically uM. The
      remarkable gradient of glutamate in the different cerebral compartments: vesicles
      > cytosol/mitochondria > extracellular fluid attests to the extraordinary
      effectiveness of glutamate transporters and the strict control of enzymes of
      glutamate catabolism and synthesis in well-defined cellular and subcellular
      compartments in the brain. A major route for glutamate and ammonia removal is via
      the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also
      removed by conversion to the inhibitory neurotransmitter gamma-aminobutyrate
      (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral
      glutamate levels are maintained by the action of glutaminase and by various alpha
      ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and
      the mitochondrial and cytosolic forms of the branched-chain aminotransferases).
      Although the glutamate dehydrogenase reaction is freely reversible, owing to
      rapid removal of ammonia as glutamine amide, the direction of the glutamate
      dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism
      rather than toward the net synthesis of glutamate, even under hyperammonemia
      conditions. During hyperammonemia, there is a large increase in cerebral
      glutamine content, but only small changes in the levels of glutamate and alpha
      ketoglutarate. Thus, the channeling of glutamate toward glutamine during
      hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5
      carbon units is accomplished in part by the ammonia-induced stimulation of the
      anaplerotic enzyme pyruvate carboxylase. Here, we suggest that glutamate may
      constitute a buffer or bulwark against changes in cerebral amine and ammonia
      nitrogen. Although the glutamate transporters are briefly discussed, the major
      emphasis of the present review is on the enzymology contributing to the
      maintenance of glutamate levels under normal and hyperammonemic conditions.
      Emphasis will also be placed on the central role of glutamate in the glutamine
      glutamate and glutamine-GABA neurotransmitter cycles between neurons and
      astrocytes. Finally, we provide a brief and selective discussion of
      neuropathology associated with altered cerebral glutamate levels. 

PMID- 27023628
TI  - Outcomes of support rod usage in loop stoma formation.
AB  - AIM: Traditionally, support rods have been used when creating loop stomas in the
      hope of preventing retraction. However, their effectiveness has not been clearly
      established. This study aimed to investigate the rate of stoma rod usage and its
      impact on stoma retraction and complication rates. METHOD: A prospective cohort
      of 515 consecutive patients who underwent loop ileostomy/colostomy formation at a
      tertiary referral colorectal unit in Sydney, Australia were studied. Mortality
      and unplanned return to theatre rates were calculated. The primary outcome
      measure of interest was stoma retraction, occurring within 30 days of surgery.
      Secondary outcome measures included early stoma complications. The 10-year
      temporal trends for rod usage, stoma retraction, and complications were examined.
      RESULTS: Mortality occurred in 23 patients (4.1 %) and unplanned return to
      theatre in 4 patients (0.8 %). Stoma retraction occurred in four patients (0.78
      %), all without rods. However, the rate of retraction was similar, irrespective
      of whether rods were used (P = 0.12). There was a significant decline in the use
      of rods during the study period (P < 0.001) but this was not associated with an
      increase in stoma retraction rates. Early complications occurred in 94/432
      patients (21.8 %) and were more likely to occur in patients with rods (64/223
      versus 30/209 without rods, P < 0.001). CONCLUSIONS: Stoma retraction is a rare
      complication and its incidence is not significantly affected by the use of
      support rods. Further, complications are common post-operatively, and the rate
      appears higher when rods are used. The routine use of rods warrants judicious
      application. WHAT DOES THIS PAPER ADD TO THE LITERATURE?: It remains unclear
      whether support rods prevent stoma retraction. This study, the largest to date,
      confirms that stoma retraction is a rare complication and is not significantly
      affected by the use of rods. Consequently, routine rod usage cannot be
      recommended, particularly as it is associated with increased stoma complications.

PMID- 27023629
TI  - Prognostic impact of lymph node dissection is different for male and female colon
      cancer patients: a propensity score analysis in a multicenter retrospective
      study.
AB  - PURPOSE: Colon cancers in male and female patients are suggested to be
      oncologically different. The aim of this study is to elucidate the prognostic
      impact of lymph node dissection (LND) in male and female colon cancer patients.
      METHODS: A total of 5941 stage I-III colon cancer patients who were curatively
      operated on during the period from 1997 to 2007 were retrospectively studied.
      Cancer-specific survival (CSS) was individually compared between for male and
      female patients treated with D3, D2, and D1 LND. Background differences of the
      patients were matched using propensity scores. RESULTS: D3, D2, and D1 LND were
      performed in 3756 (63 %), 1707 (29 %), and 478 (8 %), respectively, and more
      extensive LND was indicated for younger patients and more advanced disease. D2
      LND was significantly associated with decreased cancer-specific mortality
      compared to D1 LND in male patients (HR 0.54, 95 % CI 0.32-0.89, p = 0.04), but
      not in female patients. D3 LND did not correlate to an improved prognosis
      compared to D2 LND both in male and female patients. CONCLUSIONS: D2 LND was
      associated with an improved CSS in male, but not female colon cancer patients,
      compared to D1 LND. This suggested that colon cancer in male and female patients
      might be oncologically different, and that the prognostic impact of the extent of
      surgical intervention for colon cancer might therefore be different between
      sexes.

PMID- 27023630
TI  - Relevance of lipid metabolism for brown fat visualization and quantification.
AB  - PURPOSE OF REVIEW: Brown adipose tissue (BAT) is an emerging target to combat
      cardiometabolic disorders as it can take up substantial amounts of glucose and
      lipids from the circulation for heat production. This review focuses on new
      concepts in BAT physiology and discusses the need for new techniques to determine
      BAT activity in humans. RECENT FINDINGS: Mouse studies showed that BAT activation
      selectively increases oxidation of lipids over glucose, by recruiting fatty acids
      from intracellular triglycerides. To replenish these intracellular lipid stores,
      brown adipocytes take up both glucose and triglyceride-derived fatty acids,
      resulting in attenuation of dyslipidaemia, insulin resistance and
      atherosclerosis. Clinical studies identified the involvement of the beta3
      adrenergic receptor in BAT activation and demonstrated that human BAT activation
      also selectively increases lipid oxidation. Notably, insulin resistance during
      ageing or weight gain reduces the capacity of BAT to internalize glucose, without
      reducing fatty acid uptake or oxidative metabolism. SUMMARY: Preclinical studies
      established BAT as an important target to combat cardiometabolic disorders and
      elucidated underlying mechanisms whereas clinical studies identified therapeutic
      handles. Development of novel lipid-based PET-CT tracers and identification of
      translational biomarkers of BAT activity are required as alternatives to
      [F]fluorodeoxyglucose PET-CT to accelerate clinical development of BAT-activating
      therapeutic strategies.

PMID- 27023631
TI  - Regulation of lipid metabolism by angiopoietin-like proteins.
AB  - PURPOSE OF REVIEW: The angiopoietin-like proteins (ANGPTLs) 3, 4 and 8 have
      emerged as key regulators of plasma lipid metabolism by serving as potent
      inhibitors of the enzyme lipoprotein lipase (LPL). In this review, we provide an
      integrated picture of the role of ANGPTL3, ANGPTL4 and ANGPTL8 in lipid
      metabolism by focusing on their impact on LPL activity and plasma triglyceride
      clearance during physiological conditions such as fasting, refeeding, exercise
      and cold exposure. RECENT FINDINGS: Upon refeeding, circulating ANGPTL3 and
      ANGPTL8 promote the replenishment of white adipose tissue depots by specifically
      inhibiting LPL activity in oxidative tissues. During exercise and cold exposure,
      ANGPTL4 represses local LPL activity to assure that plasma triglycerides are
      specifically shuttled to exercising muscle and brown adipose tissue,
      respectively. Overall, ANGPTL4 is the central component of a fatty acid-driven
      feedback mechanism that regulates plasma triglyceride hydrolysis and subsequent
      tissue fatty acid uptake in response to changes in lipid availability and
      cellular fuel demand. SUMMARY: ANGPTL3, ANGPTL4 and ANGPTL8 together ensure that
      triglycerides from triglyceride-rich lipoproteins are adequately distributed
      during different physiological conditions. The impact of the ANGPTLs on plasma
      lipid levels has led to scrutiny of ANGPTLs as therapeutic targets for
      dyslipidemia.

PMID- 27023632
TI  - Preparation of hybrid organic-inorganic mesoporous silicas applied to mercury
      removal from aqueous media: Influence of the synthesis route on adsorption
      capacity and efficiency.
AB  - New hybrid organic-inorganic mesoporous silicas were prepared by employing three
      different synthesis routes and mercury adsorption studies were done in aqueous
      media using the batch technique. The organic ligands employed for the
      functionalization were derivatives of 2-mercaptopyrimidine or 2
      mercaptothiazoline, and the synthesis pathways used were post-synthesis, post
      synthesis with surface ion-imprinting and co-condensation with ion-imprinting.
      The incorporation of functional groups and the presence of ordered mesopores in
      the organosilicas was confirmed by XRD, TEM and SEM, nitrogen adsorption
      desorption isotherms, (13)C MAS-NMR, (29)Si MAS-NMR, elemental and
      thermogravimetric analysis. The highest adsorption capacity and selectivity
      observed was for the material functionalized with 2-mercaptothiazoline ligand by
      means the co-condensation with ion-imprinting route (1.03 mmol g(-1) at pH 6).
      The prepared material could be potential sorbent for the extraction of this heavy
      metal from environmental and drinking waters.

PMID- 27023633
TI  - Surface modification of Fe2TiO5 nanoparticles by silane coupling agent: Synthesis
      and application in proton exchange composite membranes.
AB  - Modifying surfaces of nanoparticles with silane coupling agent provides a simple
      method to alter their surface properties and improve their dispersibility in
      organic solvents and polymer matrix. Fe2TiO5 nanoparticles (IT) were modified
      with 3-aminopropyltriethoxysilane (APTES) as novel reinforcing filler for proton
      exchange membranes. The main operating parameters such as reaction time (R.T),
      APTES/IT and triethylamine (TEA)/IT ratios have been optimized for maximum
      grafting efficiency. The optimum conditions for R.T, APTES/IT and TEA/IT ratios
      were 6h, 4 and 0.3 respectively. It was observed that the APTES/IT and TEA/IT
      ratios were the most significant parameters affecting the grafting percentage.
      Modified nanoparticles were characterized using FT-IR, TGA, SEM, TEM and XRD
      techniques. Effects of modified nanoparticles in proton exchange membrane fuel
      cells (PEMFC) were evaluated. The resulting nanocomposite membranes exhibited
      higher proton conductivity in comparison with pristine SPPEK and SPPEK/IT
      membranes. This increase is attributed to connectivity of the water channels
      which creates more direct pathways for proton transport. Composite membrane with
      3% AIT (6.46% grafting amount) showed 0.024 S cm(-1) proton conductivity at 25 
      degrees C and 149 mW cm(-2) power density (at 0.5V) at 80  degrees C which were
      about 243% and 51%, respectively higher than that of pure SPPEK.

PMID- 27023635
TI  - Evaluation of a two rubber band technique for finger ring removal.
AB  - INTRODUCTION: Rings are required to be removed from a finger in many clinical
      situations. Rings that are difficult to remove is a problem encountered
      frequently. Many techniques have been reported for this problem. This study looks
      at the effectiveness of a single technique for removing difficult rings from
      fingers. METHODS: A two rubber band technique was used in this study of 69
      difficult to remove rings. Success of the technique and time to removal were
      recorded. RESULTS: Difficult rings were removed in 92.5% of cases, in a mean time
      of 10.7 seconds. No fingers or rings suffered damage during the study.
      CONCLUSIONS: This two rubber band technique is a rapid, safe and effective method
      for removing rings that cannot be removed easily.

PMID- 27023634
TI  - Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme
      Oxygenase-1 Expression through PI3K/Nrf2 Pathway.
AB  - Hepatitis C virus (HCV) infection-induced oxidative stress is a major risk factor
      for the development of HCV-associated liver disease. Sulforaphane (SFN) is an
      antioxidant phytocompound that acts against cellular oxidative stress and
      tumorigenesis. However, there is little known about its anti-viral activity. In
      this study, we demonstrated that SFN significantly suppressed HCV protein and RNA
      levels in HCV replicon cells and infectious system, with an IC50 value of 5.7 +/-
      0.2 MUM. Moreover, combination of SFN with anti-viral drugs displayed synergistic
      effects in the suppression of HCV replication. In addition, we found nuclear
      factor erythroid 2-related factor 2 (Nrf2)/HO-1 induction in response to SFN and
      determined the signaling pathways involved in this process, including inhibition
      of NS3 protease activity and induction of IFN response. In contrast, the anti
      viral activities were attenuated by knockdown of HO-1 with specific inhibitor
      (SnPP) and shRNA, suggesting that anti-HCV activity of SFN is dependent on HO-1
      expression. Otherwise, SFN stimulated the phosphorylation of phosphoinositide 3
      kinase (PI3K) leading Nrf2-mediated HO-1 expression against HCV replication.
      Overall, our results indicated that HO-1 is essential in SFN-mediated anti-HCV
      activity and provide new insights in the molecular mechanism of SFN in HCV
      replication. 

PMID- 27023636
TI  - Hip and knee arthroplasty implants contraindicated in obesity.
AB  - INTRODUCTION: High patient weight is a risk factor for mechanical implant failure
      and some manufacturers list obesity as a contraindication for implant use. We
      reviewed data from the 2012-2013 UK National Joint Registry to determine whether
      surgical practice reflects these manufacturer recommendations. METHODS: The
      product literature for the most commonly used hip and knee implants was reviewed
      for recommendations against use in obese patients (body mass index [BMI] >=
      30kg/m(2)). The total number of obese patients undergoing hip and knee
      arthroplasty was calculated, as was the proportion receiving implants against
      manufacturer recommendations. RESULTS: Out of 200,054 patient records, 147,691
      (74%) had a recorded BMI. The mean BMI for patients undergoing primary total hip
      arthroplasty was 29kg/m(2), compared with 31kg/m(2) for total knee arthroplasty.
      Of the 25 components reviewed, 5 listed obesity as a contraindication or
      recommended against implant use in obese patients. A total of 10,745 patients
      (16% of all obese patients) received implants against manufacturer
      recommendations. CONCLUSIONS: A high proportion of patients are receiving
      implants against manufacturer recommendations. However, there are limitations to
      using BMI for stratifying risk of implant fatigue failure and manufacturers
      should therefore provide more detailed guidelines on size specific implant load
      limits to facilitate surgical decisions.

PMID- 27023637
TI  - Primary-to-secondary care referral experience of suspected colorectal malignancy
      in young adults.
AB  - INTRODUCTION: Colorectal cancer in patients younger than 50 years of age is
      increasing steadily in the UK with limited guidelines available indicating need
      for secondary care referral. The aims of this study were to report the cancer
      incidence in those aged under 50 years referred to secondary care with suspected
      colorectal malignancy and also to analyse the quality of those referrals.
      METHODS: A total of 197 primary care referrals made between 2008 and 2014 to a UK
      district general hospital for suspected colorectal malignancy were analysed. All
      confirmed cancers were further evaluated regarding presenting symptoms, tumour
      characteristics and clinical outcomes. Each referral was given a referral
      performance score (out of 9) dependant on relevant information documented.
      RESULTS: The overall malignancy rate was 9.1% (11 male and 7 female patients).
      The median age in this cohort was 41.5 years (interquartile range [IQR]: 37-49
      years). Abdominal pain was the only presenting symptom to differ significantly
      when comparing malignant with non-malignant patients (44.4% vs 21.8%
      respectively, p=0.042). The median time period between referral date and
      colorectal specialist consultation was 11 days (IQR: 7-13 days) and the median
      referral performance score was 5 (range: 3-9). CONCLUSIONS: Malignancy is
      prevalent in patients under 50 years of age who are referred to secondary care
      for suspected colorectal cancer. Those referred with abdominal pain in the
      presence of other high risk lower gastrointestinal symptoms are at significant
      risk of having a malignancy. Major deficiencies are apparent in urgent primary
      care referrals, highlighting the need for further national guidance to aid early
      diagnosis of colorectal cancer in the young.

PMID- 27023638
TI  - Extended right hemicolectomy and left hemicolectomy for colorectal cancers
      between the distal transverse and proximal descending colon.
AB  - INTRODUCTION: We report our experience with extended right hemicolectomy (ERH)
      and left hemicolectomy (LH) for the treatment of cancers located between the
      distal transverse and the proximal descending colon, and compare postoperative
      morbidity, mortality, pathological results and survival for the two techniques.
      METHODS: A retrospective review was performed of a single institution series over
      ten years. Patients who underwent different operations, had benign disease or
      received palliative resections were excluded. Data collected were patient
      demographics, type and duration of surgery, tumour site, postoperative
      complications and histology results. RESULTS: Ninety-eight patients were analysed
      (64 ERHs, 34 LHs). ERH was conducted using an open approach in 93.8% of cases
      compared with 73.5% for LH. The anastomotic leak rate was similar for both groups
      (ERH: 6.3%, LH: 5.9%). This was also the case for other postoperative
      complications, mortality (ERH: 1.6%, LH: 2.9%) and overall survival (ERH: 50.4
      months, LH: 51.8 months). All but one patient in the ERH cohort had clear
      surgical margins. Nodal evaluation for staging was adequate in 78.1% of ERH cases
      and 58.8% of LH cases. CONCLUSIONS: In our experience, both ERH and LH are
      adequate for tumours located between the distal transverse and the proximal
      descending colon.

PMID- 27023639
TI  - Systematic review of clinical outcomes after prophylactic surgery.
AB  - Introduction Prophylactic appendicectomy is performed prior to military, polar
      and space expeditions to prevent acute appendicitis in the field. However, the
      risk-benefit ratio of prophylactic surgery is controversial. This study aimed to
      systematically review the evidence for prophylactic appendicectomy. It is
      supplemented by a clinical example of prophylactic surgery resulting in life
      threatening complications. Methods A systematic review was performed using
      MEDLINE((r)) and the Cochrane Central Register of Controlled Trials. Keyword
      variants of 'prophylaxis' and 'appendicectomy' were combined to identify
      potential papers for inclusion. Papers related to prophylactic appendicectomy
      risks and benefits were reviewed. Results Overall, 511 papers were identified,
      with 37 papers satisfying the inclusion criteria. Nine reported outcomes after
      incidental appendicectomy during concurrent surgical procedures. No papers
      focused explicitly on prophylactic appendicectomy in asymptomatic patients. The
      clinical example outlined acute obstruction secondary to adhesions from a
      prophylactic appendicectomy. Complications after elective appendicectomy versus
      the natural history of acute appendicitis in scenarios such as polar expeditions
      or covert operations suggest prophylactic appendicectomy may be appropriate prior
      to extreme situations. Nevertheless, the long-term risk of adhesion related
      complications render prophylactic appendicectomy feasible only when the short
      term risk of acute appendicitis outweighs the long-term risks of surgery.
      Conclusions Prophylactic appendicectomy is rarely performed and not without risk.
      This is the first documented evidence of long-term complications following
      prophylactic appendicectomy. Surgery should be considered on an individual basis
      by balancing the risks of acute appendicitis in the field with the potential
      consequences of an otherwise unnecessary surgical procedure in a healthy patient.

PMID- 27023640
TI  - Demystifying damage control in musculoskeletal trauma.
AB  - Trauma care has evolved rapidly over the past decade. The benefits of operative
      fracture management in major trauma patients are well recognised. Concerns over
      early total care arose when applied broadly. The burden of additional surgical
      trauma could constitute a second hit, fuelling the inflammatory response and
      precipitating a decline into acute respiratory distress syndrome, sepsis and
      multiple organ dysfunction syndrome. Temporary external fixation aimed to deliver
      the benefits of fracture stabilisation without the risk of major surgery. This
      damage control orthopaedics approach was advocated for those in extremis and a
      poorly defined borderline group. An increasing understanding of the physiological
      response to major trauma means there is now a need to refine our treatment
      options. A number of large scale retrospective reviews indicate that early
      definitive fracture fixation is beneficial in the majority of major trauma
      patients. It is recommended that patients are selected appropriately on the basis
      of their response to resuscitation. The hope is that this approach (dubbed 'safe
      definitive fracture surgery' or 'early appropriate care') will herald an era when
      care is individualised for each patient and their circumstances. The novel Damage
      Control in Orthopaedic Trauma Surgery course at The Royal College of Surgeons of
      England aims to equip senior surgeons with the insights and mindset necessary to
      contribute to this key decision making process as well as also the technical
      skills to provide damage control interventions when needed, relying on the
      improved techniques of damage control resuscitation and advances in the
      understanding of early appropriate care. 

PMID- 27023641
TI  - Withania somnifera Leaf Extract Ameliorates Benzo[a]pyrene-Induced Behavioral and
      Neuromorphological Alterations by Improving Brain Antioxidant Status in Zebrafish
      (Danio rerio).
AB  - The aquatic environment provides a sink for the environmental pollutants that
      have potential to induce oxidative stress by altering neurobehavioral response of
      aquatic animals. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon is
      known to induce oxidative stress in the brain. Withania somnifera has been used
      traditionally for its neuroprotective effect in experimental models of
      neurological disorders. The present study is aimed to evaluate the
      neuroprotective potential of Withania somnifera leaf extract (WSLE) following
      exposure to waterborne B[a]P. Wild-type zebrafish (Danio rerio) were designated
      as naive, control (dimethyl sulfoxide), WSLE, B[a]P, and B[a]P + WSLE groups.
      Behavioral studies showed reversal in scototaxis (anxiety-like) behavior in B[a]P
      group and was restored by WSLE cosupplementation in B[a]P + WSLE group. B[a]P
      induced altered antioxidant status was ameliorated by WSLE in the B[a]P + WSLE
      group. Previous studies showed that the periventricular gray zone (PGZ) of the
      optic tectum in zebrafish brain regulates scototaxis (anxiety-like) behavior. Our
      histopathological observation showed a significant increase in the pyknotic
      neuronal counts in PGZ of the B[a]P group and was ameliorated by WSLE
      cosupplementation. The study showed that the reversal in scototaxis behavior
      following exposure to waterborne B[a]P might be associated with
      neuromorphological alterations in PGZ, whereas a pioneer ethnopharmacological
      approach of WSLE cosupplementation showed its neuroprotective role to restore
      normal scototaxis of zebrafish. Future research directing toward understanding
      the role of visual circuit involved with impaired scototaxis behavior in
      zebrafish might provide new pathological outcomes following exposure to B[a]P.

PMID- 27023642
TI  - Thinking differently about lupus.
AB  - A search for the genetic causes of an autoimmune disease called systemic lupus
      erythematosus reveals a new twist on an old story.

PMID- 27023643
TI  - Correction: Tim-3 Expression in Cervical Cancer Promotes Tumor Metastasis.

PMID- 27023644
TI  - Size- and dimensionality-dependent optical, magnetic and magneto-optical
      properties of binary europium-based nanocrystals: EuX (X = O, S, Se, Te).
AB  - Europium chalcogenides (EuX, X = O, S, Se, Te), a class of prototypical
      Heisenberg magnetic semiconductors, exhibit intriguing properties in optics,
      magnetism, and magneto-optics at the nanoscale, and have broad application
      potential in optical/magnetic sensors, spintronics, optical isolators, etc. EuX
      nanocrystals (NCs) exhibit enhanced properties, such as high saturation
      magnetization, a strong magneto-optic effect (Faraday rotation), and high magneto
      resistance, which are all unanimously dependent on the NC's size, shape, and
      surface information. In this report, we give an overview of the fundamental
      properties of bulk EuX, and illustrate the quantum confinement effects on the
      optical, magnetic and magneto-optical properties of EuX nanostructures. We then
      focus on doping and self-assembly-two efficient methods that enhance magnetic
      properties by manipulating magnetic coupling in EuX nanostructures. In
      particular, we look towards future research on Eu(2+) NCs, which along with the
      overview provides an up-to-date platform for evaluating the fundamental
      properties and application potential of Eu-based semiconductors.

PMID- 27023645
TI  - Collision rates for rare cell capture in periodic obstacle arrays strongly depend
      on density of cell suspension.
AB  - Recently, computational modelling has been successfully used for determination of
      collision rates for rare cell capture in periodic obstacle arrays. The models
      were based on particle advection simulations where the cells were advected
      according to velocity field computed from two dimensional Navier-Stokes
      equations. This approach may be used under the assumption of very dilute cell
      suspensions where no mutual cell collisions occur. We use the object-in-fluid
      framework to demonstrate that even with low cell-to-fluid ratio, the optimal
      geometry of the obstacle array significantly changes. We show computational
      simulations for ratios of 3.5, 6.9 and 10.4% determining the optimal geometry of
      the periodic obstacle arrays. It was already previously demonstrated that cells
      in periodic obstacle arrays follow trajectories in two modes: the colliding mode
      and the zig-zag mode. The colliding mode maximizes the cell-obstacle collision
      frequency. Our simulations reveal that for dilute suspensions and for suspensions
      with cell-to-fluid ratio 3.5%, there is a range of column shifts for which the
      cells follow colliding trajectories. However we showed, that for 6.9 and 10.4%,
      the cells never follow colliding trajectories. 

PMID- 27023646
TI  - Five Topics Health Care Simulation Can Address to Improve Patient Safety: Results
      From a Consensus Process.
AB  - OBJECTIVES: There is little knowledge about which elements of health care
      simulation are most effective in improving patient safety. When empirical
      evidence is lacking, a consensus statement can help define priorities in, for
      example, education and research. A consensus process was therefore initiated to
      define priorities in health care simulation that contribute the most to improve
      patient safety. METHODS: An international group of experts took part in a 4-stage
      consensus process based on a modified nominal group technique. Stages 1 to 3 were
      based on electronic communication; stage 4 was a 2-day consensus meeting at the
      Utstein Abbey in Norway. The goals of stage 4 were to agree on the top 5 topics
      in health care simulation that contribute the most to patient safety, identify
      the patient safety problems they relate to, and suggest solutions with
      implementation strategies for these problems. RESULTS: The expert group agreed on
      the following topics: technical skills, nontechnical skills, system probing,
      assessment, and effectiveness. For each topic, 5 patient safety problems were
      suggested that each topic might contribute to solve. Solutions to these problems
      and implementation strategies for these solutions were identified for technical
      skills, nontechnical skills, and system probing. In the case of assessment and
      effectiveness, the expert group found it difficult to suggest solutions and
      implementation strategies mainly because of lacking consensus on metrics and
      methodology. CONCLUSIONS: The expert group recommends that the 5 topics
      identified in this consensus process should be the main focus when health care
      simulation is implemented in patient safety curricula.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.

PMID- 27023648
TI  - Contact precautions.

PMID- 27023649
TI  - A clinical approach to acid-base conundrums.
AB  - Acid-base disorders can provide essential clues to underlying patient conditions.
      This article provides a simple, practical approach to identifying simple acid
      base disorders and their compensatory mechanisms. Using this stepwise approach,
      clinicians can quickly identify and appropriately treat acid-base disorders.

PMID- 27023651
TI  - Turning point--Where are we trying to go?

PMID- 27023650
TI  - Endoscopy by nonphysicians: Conclusions based on faulty data.

PMID- 27023652
TI  - What are the latest recommendations for pneumococcal vaccines?
AB  - The Advisory Committee on Immunization Practices recently updated its guidelines
      on pneumococcal pneumonia vaccines for older adults. The new guidelines recommend
      that patients age 65 years and older receive the PCV13 vaccine in a series along
      with the PPSV23 vaccine. This article summarizes these changes along with a
      review of when to vaccinate other key adult populations.

PMID- 27023653
TI  - Abdominal pain and nausea in a 12-year-old girl.
AB  - Girls presenting with lower abdominal pain have a broad differential diagnosis.
      Transabdominal ultrasound should be performed in all girls presenting in the ED
      with lower abdominal pain. If ovarian torsion is suspected, surgical intervention
      should be initiated quickly to preserve the viability of the ovary.

PMID- 27023654
TI  - Post-ICU syndrome: Rescuing the undiagnosed.
AB  - Survivors of critical illness may develop postintensive care syndrome (PICS), a
      spectrum of conditions that include persistent cognitive dysfunction, acquired
      weakness, and intrusive memories akin to post-traumatic stress disorder.
      Relatively few ICU survivors are routinely followed in the outpatient setting by
      intensivists, but are regularly evaluated by primary care physicians and
      physician assistants in their practices. Specific and focused education about the
      key features of PICS, its effect on patients as well as family members, and
      potential therapeutic interventions may increase recognition of PICS and reduce
      its effect on survivors of critical illness.

PMID- 27023655
TI  - Unexplained chronic flank pain in a young man.

PMID- 27023656
TI  - Acute kidney injury.
AB  - Acute kidney injury (AKI) complicates up to 20% of all hospital admissions.
      Responding to the increase in admissions, complications, mortality, morbidity,
      and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert
      panel to study the issue, review the literature, and publish guidelines to
      evaluate and treat patients with AKI in the acute setting. This article reviews
      those guidelines.

PMID- 27023657
TI  - A rare cause of acute abdominal pain.

PMID- 27023658
TI  - Treating fear itself in the clinical setting.

PMID- 27023659
TI  - Shape-Controlled Metal Nanocrystals for Heterogeneous Catalysis.
AB  - The ability to control the shape of metal nanocrystals allows us to not only
      maneuver their physicochemical properties but also optimize their activity in a
      variety of applications. Heterogeneous catalysis, in particular, would benefit
      tremendously from the availability of metal nanocrystals with controlled shapes
      and well-defined facets or surface structures. The immediate benefits may include
      significant enhancements in catalytic activity and/or selectivity along with
      reductions in the materials cost. We provide a brief account of recent progress
      in the development of metal nanocrystals with controlled shapes and thereby
      enhanced catalytic performance for several reactions, including formic acid
      oxidation, oxygen reduction, and hydrogenation. In addition to monometallic
      nanocrystals, we also cover a bimetallic system, in which the two metals are
      formulated as alloyed, core-shell, or core-frame structures. We hope this article
      will provide further impetus for the development of next-generation heterogeneous
      catalysts essential to a broad range of applications. 

PMID- 27023660
TI  - Switchable Materials for Smart Windows.
AB  - This article reviews the basic principles of and recent developments in
      electrochromic, photochromic, and thermochromic materials for applications in
      smart windows. Compared with current static windows, smart windows can
      dynamically modulate the transmittance of solar irradiation based on weather
      conditions and personal preferences, thus simultaneously improving building
      energy efficiency and indoor human comfort. Although some smart windows are
      commercially available, their widespread implementation has not yet been
      realized. Recent advances in nanostructured materials provide new opportunities
      for next-generation smart window technology owing to their unique structure
      property relations. Nanomaterials can provide enhanced coloration efficiency,
      faster switching kinetics, and longer lifetime. In addition, their compatibility
      with solution processing enables low-cost and high-throughput fabrication. This
      review also discusses the importance of dual-band modulation of visible and near
      infrared (NIR) light, as nearly 50% of solar energy lies in the NIR region. Some
      latest results show that solution-processable nanostructured systems can
      selectively modulate the NIR light without affecting the visible transmittance,
      thus reducing energy consumption by air conditioning, heating, and artificial
      lighting. 

PMID- 27023661
TI  - The Energy-Water-Food Nexus.
AB  - As the global population grows in size and increasingly lives in cities, and with
      lifestyles based on greater material consumption, more attention is being given
      to the integrated system that supplies our energy, water, and food, the Nexus.
      There is also mounting concern about effects on the Nexus of climate change and
      damage to the natural environment that provides essential ecosystem services.
      Nexus analysis applies existing techniques, such as computational modelling and
      Life Cycle Assessment, but new frameworks and tools are needed, including those
      that will integrate societal and technical dimensions. Case studies show the
      vital role played by stakeholder involvement in clarifying issues, priorities,
      and values. They also demonstrate the importance of an integrated systems view of
      the complex interrelationships of the Nexus when planning effective remedies.
      Assessments conclude that transformative social and political change is needed to
      create new structures, markets, and governance to deal with the Nexus if we are
      to meet agreed-upon sustainable development goals. 

PMID- 27023662
TI  - Status of Solid State Lighting Product Development and Future Trends for General
      Illumination.
AB  - After decades of research and development on fabrication of efficient light
      emitting diodes (LEDs) throughout the visible spectrum, LED-based lighting has
      reached unparalleled performance with respect to energy efficiency and has become
      the light source for virtually all new lighting products being designed today.
      The development of the core light sources and their subsequent integration into
      lighting systems continue to present unique challenges and opportunities for
      product designers. We review these systems and the current development status, as
      well as provide context for the trends in solid state lighting that are leading
      to the development of value-added lighting solutions that extend the domain of
      lighting beyond light generation, into fields as diverse as communications,
      healthcare, and agricultural production. 

PMID- 27023664
TI  - Multilength Scale Patterning of Functional Layers by Roll-to-Roll Ultraviolet
      Light-Assisted Nanoimprint Lithography.
AB  - Top-down fabrication of nanostructures with high throughput is still a challenge.
      We demonstrate the fast (>10 m/min) and continuous fabrication of multilength
      scale structures by roll-to-roll UV-nanoimprint lithography on a 250 mm wide web.
      The large-area nanopatterning is enabled by a multicomponent UV-curable resist
      system (JRcure) with viscous, mechanical, and surface properties that are tunable
      over a wide range to either allow for usage as polymer stamp material or as
      imprint resist. The adjustable elasticity and surface chemistry of the resist
      system enable multistep self-replication of structured resist layers. Decisive
      for defect-free UV-nanoimprinting in roll-to-roll is the minimization of the
      surface energies of stamp and resist, and the stepwise reduction of the stiffness
      from one layer to the next is essential for optimizing the reproduction fidelity
      especially for nanoscale features. Accordingly, we demonstrate the continuous
      replication of 3D nanostructures and the high-throughput fabrication of
      multilength scale resist structures resulting in flexible
      polyethylenetherephtalate film rolls with superhydrophobic properties. Moreover,
      a water-soluble UV-imprint resist (JRlift) is introduced that enables residue
      free nanoimprinting in roll-to-roll. Thereby we could demonstrate high-throughput
      fabrication of metallic patterns with only 200 nm line width.

PMID- 27023667
TI  - The Essential Concepts of Nursing Cutcliffe John R McKenna Hugh The Essential
      Concepts of Nursing 368 Elsevier 9780443073724 0443073724.
AB  - It is clear that what people see in nursing is often the 'doing' bit and not the
      'knowing'. Because of this narrow view, the complexity of nursing is all too
      frequently lost in the debate.

PMID- 27023665
TI  - Selective Harvesting of Marginating-pulmonary Leukocytes.
AB  - Marginating-pulmonary (MP) leukocytes are leukocytes that adhere to the inner
      endothelium of the lung capillaries. MP-leukocytes were shown to exhibit unique
      composition and characteristics compared to leukocytes of other immune
      compartments. Evidence suggests higher cytotoxicity of natural killer cells, and
      a distinct pro- and anti-inflammatory profile of the MP-leukocyte population
      compared to circulating or splenic immunocytes. The method presented herein
      enables selective harvesting of MP-leukocytes by forced perfusion of the lungs in
      either mice or rats. In contrast to other methods used to extract lung
      leukocytes, such as tissue grinding and biological degradation, this method
      exclusively yields leukocytes from the lung capillaries, uncontaminated with
      parenchymal, interstitial, and broncho-alveolar cells. In addition, the perfusion
      technique better preserves the integrity and the physiological milieu of MP
      leukocytes, without inducing physiological responses due to tissue processing.
      This unique MP leukocyte population is strategically located to identify and
      react towards abnormal circulating cells, as all circulating malignant cells and
      infected cells are detained while passing through the lung capillaries,
      physically interacting with endothelial cells and resident leukocytes,. Thus,
      selective harvesting of MP-leukocytes and their study under various conditions
      may advance our understanding of their biological and clinical significance,
      specifically with respect to controlling circulating aberrant cells and lung
      related diseases. 

PMID- 27023668
TI  - Concordance - A Partnership in Medicine-taking Bond Christine Concordance - A
      Partnership in Medicine-taking 208 Pharmaceutical Press 9780853695721 0853695725.
AB  - This compact book outlines issues surrounding consultations that patients have
      about medications and how these can be improved to raise compliance and
      understanding.

PMID- 27023663
TI  - Thiol-Disulfide Exchange Reactions in the Mammalian Extracellular Environment.
AB  - Disulfide bonds represent versatile posttranslational modifications whose roles
      encompass the structure, catalysis, and regulation of protein function. Due to
      the oxidizing nature of the extracellular environment, disulfide bonds found in
      secreted proteins were once believed to be inert. This notion has been challenged
      by the discovery of redox-sensitive disulfides that, once cleaved, can lead to
      changes in protein activity. These functional disulfides are twisted into unique
      configurations, leading to high strain and potential energy. In some cases,
      cleavage of these disulfides can lead to a gain of function in protein activity.
      Thus, these motifs can be referred to as switches. We describe the couples that
      control redox in the extracellular environment, examine several examples of
      proteins with switchable disulfides, and discuss the potential applications of
      disulfides in molecular biology. 

PMID- 27023669
TI  - A Direct Access to 7-Aminoindoles via Iridium-Catalyzed Mild C-H Amidation of N
      Pivaloylindoles with Organic Azides.
AB  - Ir(III)-catalyzed regioselective direct C-7 amidation of indoles in reaction with
      organic azides has been developed. While its efficiency was varied by the choice
      of N-directing groups, N-pivaloylindoles were most effective in undergoing the
      desired amidation at room temperature over a broad range of substrates. The
      reaction was scalable, and deprotection of the chelation group was also facile. 

PMID- 27023673
TI  - Redesigning ACS-NSQIP Data Collection and Reports Will This Translate into Better
      Outcomes?

PMID- 27023674
TI  - Possibility of charge density wave transition in a SrPt2Sb2 superconductor.
AB  - The first-order transition at T(0) =  270 K for the platinum-based SrPt2Sb2
      superconductor was investigated using x-ray diffraction and magnetic
      susceptibility measurements. When polycrystalline SrPt2Sb2 was cooled down
      through T(0), the structure was transformed from monoclinic to a modulated
      orthorhombic structure, and no magnetic order was formed, which illustrates the
      possibility of a charge density wave (CDW) transition at T(0). SrPt2Sb2 can thus
      be a new example to examine the interplay of CDW and superconductivity in
      addition to SrPt2As2, BaPt2As2, and LaPt2Si2. It is unique that the average
      structure of the low-temperature phase has higher symmetry than that of the high
      temperature phase.

PMID- 27023670
TI  - Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by
      Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Abeta42
      Induced Tau Toxicity.
AB  - Abnormal accumulation of the microtubule-interacting protein tau is associated
      with neurodegenerative diseases including Alzheimer's disease (AD). beta-amyloid
      (Abeta) lies upstream of abnormal tau behavior, including detachment from
      microtubules, phosphorylation at several disease-specific sites, and self
      aggregation into toxic tau species in AD brains. To prevent the cascade of events
      leading to neurodegeneration in AD, it is essential to elucidate the mechanisms
      underlying the initial events of tau mismetabolism. Currently, however, these
      mechanisms remain unclear. In this study, using transgenic Drosophila co
      expressing human tau and Abeta, we found that tau phosphorylation at AD-related
      Ser262/356 stabilized microtubule-unbound tau in the early phase of tau
      mismetabolism, leading to neurodegeneration. Abeta increased the level of tau
      detached from microtubules, independent of the phosphorylation status at GSK3
      targeted SP/TP sites. Such mislocalized tau proteins, especially the less
      phosphorylated species, were stabilized by phosphorylation at Ser262/356 via PAR
      1/MARK. Levels of Ser262 phosphorylation were increased by Abeta42, and blocking
      this stabilization of tau suppressed Abeta42-mediated augmentation of tau
      toxicity and an increase in the levels of tau phosphorylation at the SP/TP site
      Thr231, suggesting that this process may be involved in AD pathogenesis. In
      contrast to PAR-1/MARK, blocking tau phosphorylation at SP/TP sites by knockdown
      of Sgg/GSK3 did not reduce tau levels, suppress tau mislocalization to the
      cytosol, or diminish Abeta-mediated augmentation of tau toxicity. These results
      suggest that stabilization of microtubule-unbound tau by phosphorylation at
      Ser262/356 via the PAR-1/MARK may act in the initial steps of tau mismetabolism
      in AD pathogenesis, and that such tau species may represent a potential
      therapeutic target for AD. 

PMID- 27023675
TI  - Towards quantitative molecular mapping of cells by Raman microscopy: using AFM
      for decoupling molecular concentration and cell topography.
AB  - Raman micro-spectroscopy (RMS) is a non-invasive technique for imaging live cells
      in vitro. However, obtaining quantitative molecular information from Raman
      spectra is difficult because the intensity of a Raman band is proportional to the
      number of molecules in the sampled volume, which depends on the local molecular
      concentration and the thickness of the cell. In order to understand these
      effects, we combined RMS with atomic force microscopy (AFM), a technique that can
      measure accurately the thickness profile of the cells. Solution-based calibration
      models for RNA and albumin were developed to create quantitative maps of RNA and
      proteins in individual fixed cells. The maps were built by applying the solution
      based calibration models, based on partial least squares fitting (PLS), on raster
      scan Raman maps, after accounting for the local cell height obtained from the
      AFM. We found that concentrations of RNA in the cytoplasm of mouse
      neuroprogenitor stem cells (NSCs) were as high as 25 +/- 6 mg ml(-1), while
      proteins were distributed more uniformly and reached concentrations as high as
      ~50 +/- 12 mg ml(-1). The combined AFM-Raman datasets from fixed cells were also
      used to investigate potential improvements for normalization of Raman spectral
      maps. For all Raman maps of fixed cells (n = 10), we found a linear relationship
      between the scores corresponding to the first component (PC1) and the cell height
      profile obtained by AFM. We used PC1 scores to reconstruct the relative height
      profiles of independent cells (n = 10), and obtained correlation coefficients
      with AFM maps higher than 0.99. Using this normalization method, qualitative maps
      of RNA and protein were used to obtain concentrations for live NSCs. While this
      study demonstrates the potential of using AFM and RMS for measuring concentration
      maps for individual NSCs in vitro, further studies are required to establish the
      robustness of the normalization method based on principal component analysis when
      comparing Raman spectra of cells with large morphological differences.

PMID- 27023676
TI  - Navigating pleiotropy in precision medicine: pharmacogenes from trauma to
      behavioral health.
AB  - A strong emerging principle in the field of precision medicine is that variation
      in any one pharmacogene may impact clinical outcome for more than one drug.
      Variants tested in the acute care setting often have downstream implications for
      other drugs impacting chronic disease management. A flexible framework is needed
      as clinicians and scientists move toward deploying automated decision support for
      gene-based drug dosing in electronic medical records. 

PMID- 27023677
TI  - Computational Catalysis Using the Artificial Force Induced Reaction Method.
AB  - The artificial force induced reaction (AFIR) method in the global reaction route
      mapping (GRRM) strategy is an automatic approach to explore all important
      reaction paths of complex reactions. Most traditional methods in computational
      catalysis require guess reaction paths. On the other hand, the AFIR approach
      locates local minima (LMs) and transition states (TSs) of reaction paths without
      a guess, and therefore finds unanticipated as well as anticipated reaction paths.
      The AFIR method has been applied for multicomponent organic reactions, such as
      the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer
      catalysis. In the presence of several reactants, many equilibrium structures are
      possible, leading to a number of reaction pathways. The AFIR method in the GRRM
      strategy determines all of the important equilibrium structures and subsequent
      reaction paths systematically. As the AFIR search is fully automatic, exhaustive
      trial-and-error and guess-and-check processes by the user can be eliminated. At
      the same time, the AFIR search is systematic, and therefore a more accurate and
      comprehensive description of the reaction mechanism can be determined. The AFIR
      method has been used for the study of full catalytic cycles and reaction steps in
      transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron
      catalyzed carbon-carbon bond formation reactions in aqueous media. Some AFIR
      applications have targeted the selectivity-determining step of transition-metal
      catalyzed asymmetric reactions, including stereoselective water-tolerant
      lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of
      establishing the selectivity of a reaction, systematic sampling of the transition
      states is critical. In this direction, AFIR is very useful for performing a
      systematic and automatic determination of TSs. In the presence of a comprehensive
      description of the transition states, the selectivity of the reaction can be
      calculated more accurately. For relatively large molecular systems, the
      computational cost of AFIR searches can be reduced by using the ONIOM(QM:QM) or
      ONIOM(QM:MM) methods. In common practice, density functional theory (DFT) with a
      relatively small basis set is used for the high-level calculation, while a
      semiempirical approach or a force field description is used for the low-level
      calculation. After approximate LMs and TSs are determined, standard computational
      methods (e.g., DFT with a large basis set) are used for the full molecular system
      to determine the true LMs and TSs and to rationalize the reaction mechanism and
      selectivity of the catalytic reaction. The examples in this Account evidence that
      the AFIR method is a powerful approach for accurate prediction of the reaction
      mechanisms and selectivities of complex catalytic reactions. Therefore, the AFIR
      approach in the GRRM strategy is very useful for computational catalysis. 

PMID- 27023678
TI  - Thiobarbituric Acid-Reactive Substances: Markers of an Acute Episode and a Late
      Stage of Bipolar Disorder.
AB  - BACKGROUND: Lowered antioxidant defense systems and increased oxidative stress
      are implicated in bipolar disorders (BD). Early and late stages of BD may present
      different biological features (including the level of oxidative stress) and may
      therefore require different treatment strategies. The aim of this study was to
      analyze serum levels of lipid peroxidation [measured as thiobarbituric acid
      reactive substances (TBARS), a derivative of malondialdehyde] in BD patients at
      various stages and phases of the illness and compare their TBARS levels with
      those of healthy controls. METHOD: A total of 129 patients (58 in the depressive
      episode, 23 in the manic episode and 48 in remission) diagnosed with type I (n =
      69) or type II (n = 60) BD and 50 healthy volunteers (control group) were
      enrolled in the study. The level of lipid peroxidation was measured in blood
      serum using a TBARS assay kit. RESULTS: TBARS levels in the acute episode of
      mania/hypomania and depression (but not in remission) were significantly higher
      than in healthy controls. With regard to the BD stage, both early- and late-stage
      BD TBARS levels were significantly increased in patients in the depressive
      episode. In late-stage BD, the TBARS level in patients in remission remained
      elevated compared with controls. A multiple regression model confirmed the
      association between the TBARS level and BD stage or acute BD. CONCLUSION: Our
      findings indicate that TBARS levels reflect the oxidative stress state which
      increases both in the acute phase of BD (mania/hypomania and depression) and with
      BD progression (stage).

PMID- 27023679
TI  - Lysine succinylation of Mycobacterium tuberculosis isocitrate lyase (ICL) fine
      tunes the microbial resistance to antibiotics.
AB  - Lysine succinylation (Ksucc) is a newly identified protein posttranslational
      modification (PTM), which may play an important role in cellular physiology.
      However, the role of lysine succinylation in antibiotic resistance remains
      elusive. Isocitrate lyase (ICL) is crucial for broad-spectrum antibiotics
      tolerance in Mycobacterium tuberculosis (Mtb). We previously found that MtbICL
      (Rv0467) has at least three succinylated lysine residues, namely K189, K322, and
      K334.To explore the effect of succinylation on the activity of MtbICL, mutants'
      mimicry of the lysine succinylation were generated by site-directed mutagenesis.
      ICL-K189E mutant strain is more sensitive than the wild-type to rifampicin and
      streptomycin, but not isoniazid. For the in vitro activity of the purified
      isocitrate lyase, only K189E mutant showed significantly decreased activity.
      Crystal structure analysis showed that Lys189 Glu dramatically increased the pKa
      of Glu188 and decreased the pKa of Lys190, whereas had negligible effect on other
      residues within 5 A as well as disruption of the electrostatic interaction
      between Lys189 and Glu182, which might prevent the closure of the active site
      loop and cause severe reduction of the enzyme activity. Considering the genetic,
      biochemical, and crystallographical evidences together, the succinylation of
      specific ICL residue can fine-tune the bacterial resistance to selected
      antibiotics. The decreased enzymatic activity resulting from the succinylation
      changed electrostatic interaction might underlie this phenotype. This study
      provided the first insight into the link between lysine succinylation and
      antibiotic resistance.

PMID- 27023680
TI  - Anion Effects on Lanthanide(III) Tetrazole-1-acetate Dinuclear Complexes Showing
      Slow Magnetic Relaxation and Photofluorescent Emission.
AB  - Three types of lanthanide complexes based on the tetrazole-1-acetic acid ligand
      and the 2,2'-bipyridine coligand were prepared and characterized by single
      crystal X-ray diffraction, IR spectroscopy, and elemental analyses; the formulas
      of these complexes are [Ln2(1-tza)4(NO3)2(2,2'-bipy)2] (Ln = Sm (1), Eu (2), Gd
      (3), Tb (4), Dy (5)), [Dy2(1-tza)4Cl2(2,2'-bipy)2] (6), and [Yb2(1
      tza)4(NO3)2(2,2'-bipy)2] (7) (1-tza = tetrazole-1-acetate and 2,2'-bipy = 2,2'
      bipyridine). They are dinuclear complexes possessing similar structures but
      different lanthanide(III) ion coordination geometries because of the distinction
      of peripheral anions (such as NO3(-) and Cl(-)) and the effect of lanthanide
      contraction. The variable-temperature magnetic susceptibilities of 1-6 were
      measured. Both Dy(III) complexes (5 and 6) display field-induced single-molecule
      magnet behaviors. Ab initio calculations revealed that the Dy(III) complex 6
      possesses a more anisotropic Dy(III) ion in comparison to that in 5. The room
      temperature photoluminescence spectra of Sm(III) (1), Eu(III) (2), Tb(III) (4),
      and Dy(III) (5 and 6) complexes exhibit strong characteristic emissions in the
      visible region, whereas the Yb(III) (7) complex shows near-infrared (NIR)
      luminescence. 

PMID- 27023681
TI  - Supplementing Public Health Inspection via Social Media.
AB  - Foodborne illness is prevented by inspection and surveillance conducted by health
      departments across America. Appropriate restaurant behavior is enforced and
      monitored via public health inspections. However, surveillance coverage provided
      by state and local health departments is insufficient in preventing the rising
      number of foodborne illness outbreaks. To address this need for improved
      surveillance coverage we conducted a supplementary form of public health
      surveillance using social media data: Yelp.com restaurant reviews in the city of
      San Francisco. Yelp is a social media site where users post reviews and rate
      restaurants they have personally visited. Presence of keywords related to health
      code regulations and foodborne illness symptoms, number of restaurant reviews,
      number of Yelp stars, and restaurant price range were included in a model
      predicting a restaurant's likelihood of health code violation measured by the
      assigned San Francisco public health code rating. For a list of major health code
      violations see (S1 Table). We built the predictive model using 71,360 Yelp
      reviews of restaurants in the San Francisco Bay Area. The predictive model was
      able to predict health code violations in 78% of the restaurants receiving
      serious citations in our pilot study of 440 restaurants. Training and validation
      data sets each pulled data from 220 restaurants in San Francisco. Keyword
      analysis of free text within Yelp not only improved detection of high-risk
      restaurants, but it also served to identify specific risk factors related to
      health code violation. To further validate our model we applied the model
      generated in our pilot study to Yelp data from 1,542 restaurants in San
      Francisco. The model achieved 91% sensitivity 74% specificity, area under the
      receiver operator curve of 98%, and positive predictive value of 29% (given a
      substandard health code rating prevalence of 10%). When our model was applied to
      restaurant reviews in New York City we achieved 74% sensitivity, 54% specificity,
      area under the receiver operator curve of 77%, and positive predictive value of
      25% (given a prevalence of 12%). Model accuracy improved when reviews ranked
      highest by Yelp were utilized. Our results indicate that public health
      surveillance can be improved by using social media data to identify restaurants
      at high risk for health code violation. Additionally, using highly ranked Yelp
      reviews improves predictive power and limits the number of reviews needed to
      generate prediction. Use of this approach as an adjunct to current risk ranking
      of restaurants prior to inspection may enhance detection of those restaurants
      participating in high risk practices that may have gone previously undetected.
      This model represents a step forward in the integration of social media into
      meaningful public health interventions. 

PMID- 27023682
TI  - A Multiscale Survival Process for Modeling Human Activity Patterns.
AB  - Human activity plays a central role in understanding large-scale social dynamics.
      It is well documented that individual activity pattern follows bursty dynamics
      characterized by heavy-tailed interevent time distributions. Here we study a
      large-scale online chatting dataset consisting of 5,549,570 users, finding that
      individual activity pattern varies with timescales whereas existing models only
      approximate empirical observations within a limited timescale. We propose a novel
      approach that models the intensity rate of an individual triggering an activity.
      We demonstrate that the model precisely captures corresponding human dynamics
      across multiple timescales over five orders of magnitudes. Our model also allows
      extracting the population heterogeneity of activity patterns, characterized by a
      set of individual-specific ingredients. Integrating our approach with social
      interactions leads to a wide range of implications. 

PMID- 27023683
TI  - Young Children's Sensitivity to Their Own Ignorance in Informing Others.
AB  - Prior research suggests that young children selectively inform others depending
      on others' knowledge states. Yet, little is known whether children selectively
      inform others depending on their own knowledge states. To explore this issue, we
      manipulated 3- to 4-year-old children's knowledge about the content of a box and
      assessed the impact on their decisions to inform another person. Moreover, we
      assessed the presence of uncertainty gestures while they inform another person in
      light of the suggestions that children's gestures reflect early developing,
      perhaps transient, epistemic sensitivity. Finally, we compared children's
      performance in the informing context to their explicit verbal judgment of their
      knowledge states to further confirm the existence of a performance gap between
      the two tasks. In their decisions to inform, children tend to accurately assess
      their ignorance, whereas they tend to overestimate their own knowledge states
      when asked to explicitly report them. Moreover, children display different levels
      of uncertainty gestures depending on the varying degrees of their informational
      access. These findings suggest that children's implicit awareness of their own
      ignorance may be facilitated in a social, communicative context. 

PMID- 27023685
TI  - Evaluation of a Therapeutic Interchange from Fluticasone/Salmeterol to
      Mometasone/Formoterol in Patients with Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Combination treatment with an inhaled corticosteroid and long-acting
      beta2-agonist is among the many treatment options for chronic obstructive
      pulmonary disease (COPD) that has been shown to improve clinical outcomes. While
      mometasone/formoterol does not currently have an FDA-approved indication for
      COPD, evidence from 2 phase 3 trials demonstrated that mometasone/formoterol can
      improve lung function and was well tolerated in patients with moderate-to-very
      severe COPD. Based on these data, a therapeutic interchange was implemented in
      the Kaiser Permanente Mid-Atlantic States region to convert patients with a COPD
      diagnosis from fluticasone/salmeterol to mometasone/formoterol. OBJECTIVE: To
      evaluate the impact of a therapeutic interchange from fluticasone/salmeterol to
      mometasone/formoterol on health outcomes in patients with COPD in a large
      ambulatory and managed care setting. METHODS: The investigators retrospectively
      reviewed the electronic medical records of patients with a COPD diagnosis who had
      a prescription for fluticasone/salmeterol converted to mometasone/formoterol
      between March 6, 2011, to March 6, 2013. Kaiser Permanente's Pharmacy and
      Therapeutics Committee provided recommended equivalent doses for conversion from
      fluticasone/salmeterol to mometasone/formoterol. Nonetheless, the final approval
      for the change in medication and selection of the dose was left to each
      physician's clinical judgment. Patients were excluded if they were (a) prescribed
      fluticasone/salmeterol 100/50 mcg, which has no equivalent mometasone/formoterol
      dose; (b) less than aged 18 years; or (c) prescribed fluticasone/salmeterol for a
      duration of less than 6 months preconversion to mometasone/formoterol. In
      addition, patients who left the Kaiser Permanente network or became deceased
      during the study period of interest were excluded. After the application of the
      inclusion and exclusion criteria, 521 patients were included in the data
      analysis. The primary endpoint was the determination of the difference in the
      occurrence of COPD exacerbations 6 months pre- and postconversion from
      fluticasone/salmeterol to mometasone/formoterol. COPD exacerbations were defined
      by the diagnosis or documentation of a COPD exacerbation during any
      hospitalizations, urgent care (UC)/emergency department (ED) visits, or clinic
      encounters. Secondary outcomes included the determination of the difference in
      the occurrence of intensive care unit admissions, hospitalizations, UC/ED visits,
      and clinic encounters for COPD exacerbations 6 months pre- and postconversion;
      number of patients who required modification in therapy; and any reasons for
      mometasone/for-moterol discontinuation postconversion. Patients served as their
      own controls to compare any differences in outcomes while taking
      mometasone/formoterol versus fluticasone/salmeterol. RESULTS: Within our patient
      population, 34.2% (n = 178) of patients experienced at least 1 COPD exacerbation
      while prescribed fluticasone/salmeterol compared with 28.6% (n = 149) of patients
      while prescribed mometasone/formoterol (P = 0.030). Mometasone/formoterol therapy
      did not demonstrate any statistically significant differences in the secondary
      outcomes (P < 0.050). A later subgroup analysis of the primary outcome revealed
      that factors associated with a statistically significant decrease in the
      occurrence of COPD exacerbations were male sex (P = 0.023), comorbid asthma (P =
      0.026), and conversion from fluticasone/salmeterol to a more potent dose of
      mometasone/formoterol (P = 0.014). CONCLUSIONS: There was a statistically
      significant decrease in the proportion of patients who experienced COPD
      exacerbations postconversion from fluticasone/salmeterol to
      mometasone/formoterol. This study is an example of a real-world therapeutic
      interchange that provides additional data to support the use of
      mometasone/formoterol for its unlabeled COPD indication. DISCLOSURES: No outside
      funding supported this study. The authors report no financial or other conflicts
      of interest related to the subject of this article. All authors contributed to
      study design and manuscript revision. Yip collected and analyzed data and
      prepared the manuscript.

PMID- 27023684
TI  - Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against
      Influenza in Mice.
AB  - The widespread influenza virus infection further emphasizes the need for novel
      vaccine strategies that effectively reduce the impact of epidemic as well as
      pandemic influenza. Conventional influenza vaccines generally induce virus
      neutralizing antibody responses which are specific for a few antigenically
      related strains within the same subtype. However, antibodies directed against the
      conserved stalk domain of HA could neutralize multiple subtypes of influenza
      virus and thus provide broad-spectrum protection. In this study, we designed and
      constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that
      expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on
      the viral envelope. We demonstrated that repeated intranasal immunizations with
      rBac-HA virus induced HA stalk-specific antibody responses and protective
      immunity against homologous as well as heterosubtypic virus challenge. The
      adoptive transfer experiment shows that the cross-protection is conferred by the
      immune sera which contain HA stalk-specific antibodies. These results warrant
      further development of rBac-HA virus as a broad-protective vaccine against
      influenza. The vaccine induced protection against infection with the same subtype
      as well as different subtype, promising a potential universal vaccine for broad
      protection against different subtypes to control influenza outbreaks including
      pandemic. 

PMID- 27023686
TI  - Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to
      Severe Chronic Kidney Disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for
      developing gout and having refractory disease. Gout flare prevention relies
      heavily on urate-lowering therapies such as allopurinol and febuxostat, but
      clinical decision making in patients with moderate-to-severe CKD is complicated
      by significant comorbidity and the scarcity of real-world cost-effectiveness
      studies. OBJECTIVE: To compare total and disease-specific health care
      expenditures by line of therapy in allopurinol and febuxostat initiators after
      diagnosis with gout and moderate-to-severe CKD. METHODS: A retrospective
      observational cohort study was conducted to compare mean monthly health care cost
      (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated
      allopurinol or febuxostat. The primary outcome was total mean monthly health care
      expenditures, and the secondary outcome was disease-specific (gout, diabetes,
      renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM
      274.xx) aged >= 18 years with concurrent CKD (stage 3 or 4) were selected from
      the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat
      initiation. Patients were followed until disenrollment, discontinuation of the
      qualifying study agent, or use of the alternate study agent. Patients initiating
      allopurinol were subsequently propensity score-matched (1:1) to patients
      initiating febuxostat. Five generalized linear models (GLMs) were developed, each
      controlling for propensity score, to identify the incremental costs (vs.
      allopurinol) associated with febuxostat initiation in first-line (without prior
      allopurinol exposure) and second-line (with prior allopurinol exposure) settings.
      RESULTS: Propensity score matching yielded 2 cohorts, each with 1,486 patients
      (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had
      stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was
      well balanced on numerous comorbidities and medication exposures with the
      following exception: 50.0% of febuxostat initiators were treated in the second
      line setting; that is, they had baseline exposure to allopurinol, whereas only
      4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted
      mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM
      results suggest that first-line febuxostat users incurred significantly (P =
      0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line
      febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs.
      $1,487). Febuxostat initiators in both settings had significantly (P < 0.001)
      higher gout-specific cost, due to higher febuxostat acquisition cost. Increased
      gout-specific cost in the first-line febuxostat cohort was offset by
      significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86
      vs. $216). There were no significant differences in either renal or CVD costs
      (adjusted) between allopurinol initiators treated almost exclusively in the first
      line setting and second-line febuxostat patients. CONCLUSIONS: Gout patients with
      concurrent CKD, initiating treatment with febuxostat in a first-line setting,
      incurred significantly less total cost than patients initiating allopurinol
      during the first exposure to each agent. Conversely, patients treated with second
      line febuxostat following allopurinol incurred significantly higher total cost
      than patients initiating allopurinol. There was no significant difference in
      total cost between the agents across line of therapy. Although study findings
      suggest the potential for CVD and renal-related savings to offset febuxostat's
      higher acquisition cost in gout patients with moderate-to-severe CKD, this is the
      first such retrospective evaluation. Future research is warranted to both
      demonstrate the durability of study findings and to better elucidate the
      mechanism by which associated cost offsets occur. DISCLOSURES: No outside funding
      supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A.
      Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time
      of this study. Tidwell and Schulman are employees of Outcomes Research Solutions,
      consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the
      design of the study and to the writing and review of the manuscript. All authors
      read and approved the final manuscript. Tidwell and Schulman collected the data,
      and all authors participated in data interpretation.

PMID- 27023687
TI  - Drug Product Life-Cycle Management as Anticompetitive Behavior: The Case of
      Memantine.
AB  - A "product hop" involves the substitution of a new formulation of a prescription
      drug by a pharmaceutical manufacturer for an old version to forestall generic
      competition. In 2015, for example, Forest Laboratories, the brand-name drug
      manufacturer of memantine, an Alzheimer's disease treatment, introduced an
      extended-release version and tried to restrict patient access to the previous
      version. Product hops can lead to useful incremental innovation but can also have
      major public health implications by disrupting patients on stable treatment
      regimens and increasing costs for patients and payers. This commentary reviews
      alleged anticompetitive product hopping in the case of memantine, which involved
      proposed conduct that would have left Alzheimer's disease patients with no
      effective choice but to transition to memantine XR. Policy solutions that can
      limit anticompetitive product hops include raising the bar for obtaining patents
      on new drug product formulations and changing automatic generic substitution
      laws. DISCLOSURES: No outside funding supported this research. To support his
      work at PORTAL in the summer of 2015, Capati was the recipient of the University
      of New Hampshire School of Law Rudman Center Public Service Fellowship.
      Kesselheim's research was supported by Greenwall Faculty Scholars program, the
      Laura and John Arnold Foundation, and the Harvard Program in Therapeutic Science.
      In 2013, Kesselheim served as an expert on behalf of a class of individual
      plaintiffs against Warner Chilcott regarding potential antitrust violations
      Kesselheim was responsible for concept and design of this commentary. Capati took
      the lead in data collection and analysis, along with Kesselheim. Capati wrote the
      manuscript, which was revised by primarily by Kesselheim, along with Capati.

PMID- 27023688
TI  - Evaluation of Abuse-Deterrent or Tamper-Resistant Opioid Formulations on Overall
      Health Care Expenditures in a State Medicaid Program.
AB  - BACKGROUND: The development of abuse-deterrent opioid prescription medications is
      a priority at the national level. Pharmaceutical manufacturers have begun
      marketing new formulations of currently available opioids that meet higher abuse
      resistance standards. Little information is available regarding the impact of
      these formulations on overall health care expenditures. OBJECTIVES: To (a)
      examine the relationship between health care expenditures and use of brand abuse
      deterrent or tamper-resistant (ADTR) extended-release opioids versus standard
      dosage form (SDF) extended-release opioids in a state Medicaid population, and
      (b) determine whether this relationship was influenced by member-specific
      characteristics. METHODS: The study is a cross-sectional review of Oklahoma
      Medicaid members (aged >= 21 years) with at least 1 paid pharmacy claim for long
      acting opioids between September 2013 and August 2014. Members who were adherent
      to extended-release opioid products were classified into ADTR and SDF opioid
      groups. The relationship between health care expenditures (prescription, medical,
      and overall) and opioid groups was examined using multiple linear regression
      models. The impact of member-specific characteristics (age, sex, race, urban
      classifications, and various comorbidities) on this relationship was examined.
      RESULTS: Prescription spending ($9,265,554) accounted for 35% of overall health
      care expenditures ($26,304,693) among 938 members during the 12-month reference
      period. Total prescription expenditures were higher among ADTR than SDF user
      groups, and the difference in median expenditures between these 2 groups was
      larger among members with more comorbidities, as measured by the Charlson
      Comorbidity Index score. Overall, ADTR users had higher median total health care
      and medical expenditures, and the difference in median expenditures was dependent
      on whether a member had comorbidities of addiction or not (higher expenditures
      were observed among members with comorbidities of addiction). CONCLUSIONS: The
      abuse and misuse of medically prescribed opioid products is a growing health
      epidemic. A variety of attempts have been made to reduce the potential of abuse
      and misuse of these products, including changes to product formulations. The
      results of this study indicate that both prescription spending and physician and
      pharmacy spending combined may be increased with the use of these new products
      because of higher pricing. Study findings also suggest that the use of ADTR
      opioids among members with comorbidities of addiction may be related to slightly
      lower overall health care and medical expenditures than those among members
      without comorbidities of addiction. Further research is required to answer
      questions regarding the comparative effectiveness of existing opioid prescription
      formulations. DISCLOSURES: No outside funding supported this research. Nesser is
      employed by the Oklahoma Health Care Authority, and Keast is a contractual
      employee for the Oklahoma Health Care Authority. The authors declare no other
      conflicts of interest. Study design was primarily contributed by Keast, along
      with Nesser and Farmer. Keast took the lead in data collection, while data
      interpretation was primarily performed by Owora, along with Keast and assisted by
      Nesser and Farmer. The manuscript was written and revised by all authors equally.

PMID- 27023689
TI  - Opioid Treatment Patterns Following Prescription of Immediate-Release
      Hydrocodone.
AB  - BACKGROUND: Immediate-release (IR) hydrocodone is the most widely prescribed
      opioid in the United States; however, little is known about the utilization
      patterns and duration of opioid use among patients prescribed IR hydrocodone. A
      better understanding of the use of IR hydrocodone would result in more
      appropriate prescribing patterns of extended-release opioids. OBJECTIVE: To
      assess downstream length of opioid therapy and utilization patterns of extended
      release/long-acting (ER/LA) opioids among patients on IR hydrocodone to provide a
      better understanding of how IR and ER/LA opioids are used to manage pain.
      METHODS: Retrospective analysis using health care claims from the Truven
      MarketScan Commercial, Medicare Supplemental, and Medicaid databases was
      performed. Patients prescribed IR hydrocodone during the 6-month baseline period
      (July 2011-December 2011) and with continuous enrollment for a 12-month follow-up
      period (2012) post-index date (January 1, 2012) were selected. Downstream length
      of therapy, defined as number of days supplied with opioids, and downstream use
      of ER/LA opioids during follow-up were examined by average pills per month (<= 60
      vs. > 60 pills per month) and days supply (< 60 vs. >= 60 days supply) of IR
      hydrocodone during baseline to mimic intermittent and consistent IR users.
      RESULTS: At baseline, 1,743,933 commercial, 277,096 Medicare, and 157,922
      Medicaid IR hydrocodone patients were identified. During follow-up, 1.7%, 2.9%,
      and 2.8% of patients initiated (i.e., converted to or newly started) ER/LA
      opioids for commercial, Medicare, and Medicaid groups, respectively.
      Approximately 90% of patients were prescribed IR hydrocodone for less than 2
      months in the following year, while 10% were high utilizers, averaging nearly 8
      months of prescribed opioid use during follow-up. Downstream initiation of ER/LA
      opioids was significantly higher among commercial patients prescribed IR
      hydrocodone for > 60 pills per month than with <= 60 pills per month (7.8% vs.
      1.2%, respectively, P < 0.05) at baseline. For commercial patients initiating
      ER/LA opioids, length of ER/LA therapy during follow-up was significantly longer
      among patients with baseline IR hydrocodone > 60 pills per month than with <= 60
      pills per month. All results were consistent when examined by levels of days
      supply. CONCLUSIONS: A majority of the population prescribed IR hydrocodone was
      not prescribed opioid therapy beyond 2 months on average in the 1-year follow-up
      period. Only a small subset of patients with increased pills per month or days
      supply of IR hydrocodone in the baseline period continued to be high utilizers in
      the following year, averaging nearly 8 months of prescribed opioid use. A limited
      proportion of patients prescribed IR hydrocodone converted to ER/LA opioids. This
      knowledge can assist policymakers and physicians, providing an opportunity to
      identify small subsets of patients to improve ER/LA opioid prescribing.
      DISCLOSURES: Funding and support for this study was provided by Purdue Pharma
      L.P. Consulting fees were paid to Evidera by Purdue Pharma L.P. for this study.
      Kansal, Chitnis, and Paramore are employees of Evidera and were paid consultants
      to Purdue Pharma for this research. Holly is an employee for Purdue Pharma, and
      Bell and Ben-Joseph were full-time employees of Purdue Pharma during the design,
      planning, and execution of the studies and during the preparation of this
      manuscript. Burgoyne and Brixner were consultants on this project. Study design
      was created by Ben-Joseph, Brixner, Paramore, and Burgoyne. Data were collected
      by Kansal, Chitnis, Bell, Ben-Joseph, and Holly and interpreted by Ben-Joseph,
      Bell, Kansal, and Holly, with assistance from Brixner, Paramore, Burgoyne, and
      Chitnis. The manuscript was written by Ben-Joseph, Bell, Paramore, Chitnis, and
      Holly, with assistance from Kansal, and revised by Bell and Holly, along with Ben
      Joseph, Brixner, Kansal, Paramore, Burgoyne, and Chitnis.

PMID- 27023690
TI  - Assessment of the Level of Satisfaction and Unmet Data Needs for Specialty Drug
      Formulary Decisions in the United States.
AB  - BACKGROUND: Formulary management within a limited budget is critical, especially
      for specialty drugs, which are used for serious medical conditions and are very
      expensive. Despite attempts to summarize the pertinent evidence, it is uncertain
      whether data needs of formulary decision makers for specialty drugs are
      satisfied. OBJECTIVE: To assess the level of satisfaction of specialty drug
      formulary decision makers with regards to the strength of current available data
      sources and unmet needs regarding clinical, economic, and unpublished evidence.
      METHODS: This study targeted pharmacists and physicians involved with formulary
      decision making at health plans or pharmacy benefit management companies at the
      national, large regional, and local levels. 95 individuals were invited to
      participate (without compensation) in a 21-item, web-based survey (Qualtrics),
      which was open from June 14 to July 31, 2014. The responses were coded for
      descriptive and statistical analysis. Statistical analyses included the Kruskal
      Wallis test, analysis of variance, and the Mann-Whitney-Wilcoxon test. RESULTS:
      Of 95 pharmacists or physicians, 40 respondents initiated the survey, and 33
      respondents completed the survey (response rate = 34.7%). Drug formulary decision
      makers infrequently rated data evidence strength (17.1% "always"). Clinical data
      evidence strength was rated highest with published randomized controlled trials
      (RCTs; mean [SD] = 4.06 [0.87] of 5.0), while participant organizations' internal
      data were rated highest for economic data evidence strength (mean [SD] = 3.91
      [1.07] of 5.0). Decision makers rated the highest unmet need as more data
      generated from head-to-head RCTs (mean [SD] = 2.94 [0.25] of 3.0) and cost
      effectiveness analyses (mean [SD] = 2.53 [0.67] of 3.0). The participants
      believed manufacturers might be in the best position to satisfy their desire for
      head-to-head RCTs (mean [SD] = 4.31 [1.09] of 5.0). CONCLUSIONS: Despite a
      variety of data sources, drug formulary decision makers continue to rely on
      published RCTs or internal economic analyses as having the strongest evidence
      strength. The study respondents believed that pharmaceutical manufacturers would
      be best able to satisfy the greatest clinical data unmet need, that is, head-to
      head RCTs in specialty drug formulary decisions. DISCLOSURES: This study was not
      funded by any company or pharmaceutical manufacturer. Navarro has worked as a
      consultant for Biogen, Purdue Pharma, and Novartis and has offered expert
      testimony on behalf of AstraZeneca. The authors declare no other potential
      conflicts of interest. Study design was contributed primarily by Navarro, along
      with Choi. Choi took the lead in data collection and interpretation, assisted by
      Navarro. Both authors contributed equally to manuscript writing and revision.

PMID- 27023691
TI  - Connecting Patients to Prescription Assistance Programs: Effects on Emergency
      Department and Hospital Utilization.
AB  - BACKGROUND: Manufacturer prescription assistance programs (PAPs) have been
      developed to provide medications at little or no cost to eligible patients. There
      are over 200 PAPs available from pharmaceutical companies, and each may have
      different eligibility requirements and assistance guidelines. A formalized
      community-based patient prescription coordinator can help patients navigate these
      programs by reviewing an applicant's financial information and medication
      requirements to identify which PAPs are most appropriate. Little is known,
      however, about whether providing such guidance is associated with a reduction in
      acute care utilization. OBJECTIVE: To evaluate changes in emergency department
      and hospital utilization among patients who received care coordination and
      financial assistance with prescribed medications. METHODS: This single-cohort
      interrupted time-series study included participants in eastern Washington state
      who enrolled in the Spokane Prescription Assistance Network (SPAN) program
      between March 1, 2009, and August 31, 2012. Referrals to the SPAN patient
      prescription coordinator were made by a social service agency or medical provider
      for patients who may have difficulty paying for prescribed medications. Initial
      patient contact occurred while the patient was still being treated in a clinic or
      hospital or through a direct visit to the coordinator's community-based office.
      Participants were contacted 6 months after the initial appointment and then
      annually thereafter to review current medications and health status. A review of
      electronic health records provided information on hospitalizations and emergency
      department visits in the 12 months before and after program entry. RESULTS: Among
      SPAN participants (n = 310), emergency department and hospital encounters
      declined from 0.38 per participant in the year before enrollment to 0.20
      encounters in the year following program entry. A repeated-measures mixed-effects
      model indicated SPAN participation was associated with a 51% decline in the rate
      of emergency department and hospital utilization (incidence rate ratio [IRR] =
      0.49; 95% CI = 0.31-0.77; P = 0.002). Observed effects differed by prescription
      class. Factor interactions revealed significant reductions in utilization for
      participants with prescribed pulmonary medications (IRR = 0.58; 95% CI = 0.37
      0.92; P = 0.019). Assistance with mental health (psychotropic) medications was
      associated with increased incidence of utilization (IRR = 2.07; 95% CI = 1.32
      3.24; P = 0.001). At the time of SPAN enrollment, 60% of participants had
      prescriptions for psychotropic medications. CONCLUSIONS: A formalized patient
      prescription coordinator can help patients access prescribed medications at low
      cost and remain compliant with treatment plans. In a study of a coordination
      pilot program, reductions in hospital admissions and emergency department visits
      were observed following program participation. DISCLOSURES: This study was not
      supported by any outside funding. The authors declare no conflicts of interest.
      Study design was created by Burley, McPherson, and Daratha. Burley Daratha,
      Selinger, and Armstrong collected the data, with interpretation performed by
      Burley, Daratha, and Tuttle, assisted by McPherson. The manuscript was written by
      Burley, Daratha, and Selinger, with assistance from White, and revised by Burley,
      White, and Selinger, with assistance from Daratha and Tuttle.

PMID- 27023692
TI  - Effect of Clinical and Attitudinal Characteristics on Obtaining Comprehensive
      Medication Reviews.
AB  - BACKGROUND: Comprehensive medication reviews (CMRs) consist of in-depth reviews
      of patients' medications to identify effectiveness or safety problems and often
      generate cost savings for individuals. Despite their advantages, CMRs are not
      widely obtained. Previous studies found that older age, female sex, and
      experience of side effects were associated with obtaining a medication review.
      OBJECTIVE: To quantify the association between attitudinal and clinical factors
      with intention and predict future behavior to obtain a CMR among Medicare Part D
      beneficiaries. METHODS: A sample of Medicare Part D beneficiaries from 1 health
      care plan (n = 660) completed a 14-item survey over the telephone assessing
      factors that were hypothesized to affect their intention and behavior to obtain a
      CMR. The survey collected medication use history and health care information with
      the medication user self-evaluation tool, health status, adherence, intention to
      obtain a CMR, and demographic characteristics. Subjects subsequently were
      informed that they could obtain a CMR from their pharmacies. Claims data were
      obtained that indicated which subjects received a CMR. Two dependent variables
      were predicted: intention to schedule a CMR using a multivariate linear
      regression model and receipt of a CMR using a logistic regression and including
      intention as a predictor variable. RESULTS: The mean age of participants was 76.6
      (SD = 7.61) years; 71% were female; and participants took an average of 5.2 (SD =
      3.18) medications. The intention to have a CMR was 2.85 (SD = 1.41) on a 5-point
      scale, and 5.6% of the participants actually had a CMR. Worrying about
      medications doing more harm than good, number of pharmacies where participants
      obtained their medications from, number of medications, and number of medical
      conditions predicted intention to obtain a CMR. Patients who perceived their
      health status to be poorer compared with others their age were more likely to
      have a CMR. Intention to obtain a CMR was not associated with receipt of a CMR.
      CONCLUSIONS: Stakeholders should target patients who perceive their health to be
      poor for a CMR, hence expanding the scope of CMRs and increasing the number of
      older adults benefiting from this service. DISCLOSURES: This study was funded by
      a grant from the Agency for Healthcare Research and Quality (1R18HS018353). Frank
      is an employee of Outcomes MTM. Pendergast has received grants from the NIH, NIA,
      and PICORI. Farris has received grants from NIH and speaker fees from
      Chulalongkorn University, Bangkok, Thailand, and the American College of Clinical
      Pharmacy. All other authors declare that they have no conflicts of interest.
      Study concept was developed by Farris, Pendergast, Chrischilles, and Doucette.
      Pendergast, Frank, Farris, and Aneese collected the data, with assistance from
      Chrischilles and Doucette. Data interpretation was performed by Farris, Marshall,
      Salgado, and Aneese, with assistance from the other authors. The manuscript was
      written by Farris, Salgado, and Aneese, with assistance from the other authors,
      and revised by Salgado and Marshall, assisted by the other authors.

PMID- 27023693
TI  - Patient Characteristics, Health Care Resource Utilization, and Costs Associated
      with Treatment-Regimen Failure with Biologics in the Treatment of Psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic, incurable, and immune-mediated skin disorder
      that is characterized by erythematous scaly papules and plaques. Understanding of
      psoriasis at the molecular level has led to the development of biologic agents
      that target disease-specific inflammatory mediators in psoriatic lesions.
      Biologic agents have become important components of the psoriasis armamentarium,
      but some patients become refractory to these agents over time or fail to respond
      to subsequent biologics. OBJECTIVES: To (a) evaluate demographic and clinical
      characteristics of psoriasis patients who have treatment patterns suggestive of
      failure to a newly initiated biologic agent (treatment-regimen failures) compared
      with those who do not (non-treatment-regimen failures) and (b) to assess health
      care-related resource utilization and costs in non-treatment-regimen failures and
      treatment-regimen failures. METHODS: In this retrospective observational cohort
      study, patients were selected from the MarketScan claims database of commercially
      insured individuals and individuals with Medicare supplemental insurance. The
      index event was a newly initiated biologic agent for the treatment of psoriasis
      (etanercept, adalimumab, ustekinumab, or infliximab) between January 2010 and
      December 2011. The analysis included psoriasis patients aged >= 18 years with >=
      1 prescription claim for a biologic and continuous enrollment 12 months pre- and
      post-index date. Patients with claims for a biologic in the pre-index period were
      excluded. Patients were divided into treatment-regimen-failure and non-treatment
      regimen-failure groups based on their treatment patterns post-index date. The
      treatment-regimen-failure group included patients who switched to another
      biologic, discontinued the biologic without restarting, increased the dose of the
      biologic, or augmented treatment with a nontopical psoriasis medication during
      the post-index period. Between-group patient characteristics and medication use
      were compared using analysis of variance for continuous variables and chi-square
      tests for categorical variables without adjustment. Cost differences were
      compared using the propensity score-adjusted bin bootstrapping method. RESULTS:
      Overall, 2,146 patients met the enrollment criteria. The mean age was 45.1 years.
      Of these patients, 41.5% were considered treatment-regimen failures. Among
      treatment-regimen failures, 53% were females, and among non-treatment-regimen
      failures, 61% were male. Patients who experienced treatment-regimen failure had
      higher incidences of comorbid cerebrovascular disease, hypertension, chronic
      pulmonary disease, depression, and anxiety in the pre-index period and were more
      likely to use concomitant topicals (67.0% vs. 58.4%; P < 0.001), methotrexate
      (20.2% vs. 7.3%; P < 0.001), and cyclosporine (3.1% vs. 1.0%; P < 0.001) in the
      post-index period. Mean total all-cause health care costs were higher in patients
      with treatment-regimen failure versus non-treatment-regimen failure during the
      pre-index period ($8,024 vs. $6,637; P = 0.002), but patients with non-treatment
      regimen failure had higher all-cause costs ($30,759 vs. $28,012; P = 0.002) and
      psoriasis-related costs ($25,286 vs. $19,625; P < 0.001) during the post-index
      period. CONCLUSIONS: The results of the current study demonstrated that psoriasis
      patients with treatment patterns suggestive of treatment-regimen failure on an
      index biologic had different characteristics and incurred higher all-cause health
      care costs than did patients without treatment-regimen failure during the pre
      index period. This study was supported by Eli Lilly and Company. Foster, Zhu,
      Guo, Nikai, Malatestinic, Ojeh, and Goldblum are full-time employees and
      stockholders of Eli Lilly and Company. Kornberg is a full-time employee of INC
      Research, which was contracted by Eli Lilly to assist with medical writing. Wu
      has received research funding from AbbVie, Amgen, Coherus Biosciences, Eli Lilly,
      Janssen, Merck, Novartis, Pfizer, Regeneron, and Sandoz; he is a consultant for
      AbbVie, Amgen, Celgene, Dermira, DUSA Pharmaceuticals, Eli Lilly, and Pfizer.
      Study concept was developed by Foster, Ojeh, Malatestinic, and Goldblum. Zhu and
      Guo, along with Foster, took the lead in data collection, and data interpretation
      was performed by Nikai, Wu, and Foster, with assistance from the other authors.
      The manuscript was primarily written by Kornberg, along with Foster, with
      assistance from the other authors. All of the authors were involved with
      manuscript revision.

PMID- 27023694
TI  - Health Resource Utilization and Cost for Patients with Incontinent Overactive
      Bladder Treated with Anticholinergics.
AB  - BACKGROUND: Overactive bladder (OAB) is a common medical condition with
      significant economic and humanistic burden. Inadequately managed OAB may
      exacerbate or result in comorbidities such as depression, falls, and urinary
      tract infections, which can further increase the burden to the health care
      system. Anticholinergics are often prescribed for management of OAB with urinary
      incontinence ("wet" OAB). However, research has shown that patient adherence and
      persistence to anticholinergic therapy is poor, with approximately 80% of
      patients ultimately failing their first prescribed anticholinergic medication
      within the first year. While there has been a fair amount of research on the
      economic burden of OAB, the real-world impact of initiating anticholinergic
      therapy in patients with wet OAB has not been well studied. OBJECTIVE: To compare
      falls/fractures, anxiety/depression, health care resource utilization, and health
      care costs between a cohort of patients with wet OAB who initiated
      anticholinergic therapy and a matched cohort of patients without OAB. METHODS:
      This study was a retrospective medical and pharmacy claims analysis. Cases were
      members of a primary care-based, multispecialty physician medical group located
      in California. Cases were eligible for inclusion if they were prescribed
      anticholinergic therapy between January 2008 and May 2012 based on pharmacy
      claims, had a diagnosis of OAB, and reported having >= 1 urinary incontinence
      episode per day. Wet OAB cases were matched to non-OAB controls in a 1:3 ratio
      based on sex, age, and observation time. Medical and pharmacy claims data were
      used to analyze patient comorbidities, as well as track health care resource
      utilization (HRU) and direct payer costs. RESULTS: After initiating
      anticholinergic therapy, wet OAB patients had a 46% higher adjusted risk of
      experiencing falls/fractures (P < 0.001) and a 33% higher adjusted risk of
      experiencing depression/anxiety (P = 0.022) than non-OAB patients. Wet OAB was
      significantly associated with increased HRU rates of hospital admissions,
      outpatient visits, prescriptions filled, and diagnostic tests performed. After
      adjustment for covariates, total health care cost was 33% higher for wet OAB
      patients than non-OAB patients, resulting in an increased cost of $1,746 per
      member per year. CONCLUSIONS: The findings of this research suggest OAB patients
      who initiate anticholinergic therapy and still experience incontinence are at a
      greater risk for comorbidities such as falls/fractures and depression/anxiety,
      and use significantly more health care resources, than patients without OAB.
      Programs to improve patient monitoring and referrals, the appropriate use of
      alternative treatments within guidelines, and adherence to evidence-based
      practice parameters may improve clinical outcomes and decrease HRU for these
      patients. DISCLOSURES: This study was sponsored by Allergan, Irvine, California,
      which reviewed and approved the final manuscript. At the time of the study,
      Yehoshua had received a fellowship at the University of Arizona, which was funded
      by Allergan. Yehoshua, Joshi, and Campbell are employees of Allergan. Vasaveda
      has received consulting fees from Allergan, Medtronic, and Boston Scientific.
      Chancelor has received consulting fees from Allergan and Medtronic. All authors
      met the ICMJE authorship criteria. Neither honoraria nor payments were made for
      authorship. Study design was created by Yehoshua, Pulicharam, Malone, and
      Armstrong. Pulicharam took the lead in data collection, along with Chancellor and
      Campbell, and data interpretation was performed by Chancellor, Vasavada, Malone,
      and Armstrong. The manuscript was written by Yehoshua and revised by Joshi and
      Yehoshua, with assistance from the other authors.

PMID- 27023695
TI  - Patterns and Economic Burden of Hospitalizations and Exacerbations Among Patients
      Diagnosed with Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare and fatal restrictive
      respiratory disease under the idiopathic lung disease (ILD) class. IPF is a form
      of chronic, progressive fibrosing interstitial pneumonia and has more scarring,
      less inflammation, and poorer prognosis than most other ILD forms. Exacerbation
      of IPF is rapid, with unpredictable deterioration of lung function, and is
      associated with short-term mortality. The American Thoracic Society (ATS)
      evidence-based guidelines for diagnosis and management of IPF reports that the
      incidence of acute exacerbations is between 5%-10%. Limited real-world evidence
      has been identified in the United States that assesses patterns of
      hospitalization, exacerbation of IPF, and the associated economic burden.
      OBJECTIVES: To (a) characterize patients newly diagnosed with IPF and (b) examine
      incidence rates and costs of all-cause hospitalizations, IPF-related
      hospitalizations, and exacerbations. METHODS: A retrospective analysis was
      performed with a national commercial claims database from calendar years 2006 to
      2011. Newly diagnosed IPF patients were identified with either >= 2 claims for
      idiopathic fibrosing alveolitis (IFA) or >= 1 claim for IFA and >= 1 claim for
      postinflammatory pulmonary fibrosis and a lung biopsy or thoracic high-resolution
      computed tomography within 90 days of the first claim for IFA (index date). IPF
      related hospitalizations and possible IPF exacerbations were defined based on
      diagnoses recorded on event claims. Frequency, incidence rate, duration of
      events, and associated costs from the third-party payer's perspective were
      estimated. RESULTS: Among 1,735 identified IPF patients, 38.6% had at least 1 all
      cause hospitalization; 10.8% had IPF-related hospitalizations; 4.6% had suspected
      IPF exacerbations leading to hospitalization; and 72.1% had suspected IPF
      exacerbations leading to urgent outpatient visits during the 1-year post-index
      period. Incident rates for these 4 events were 83 (95% CI = 79-88), 17 (95% CI =
      14-19), 7 (95% CI = 6-9), and 277 (95% CI = 269-286) per 100 person-years,
      respectively. Average costs per event were $13,987 (SD = $41,988), $16,812 (SD =
      $66,399), $14,731 (SD = $85,468), and $444 (SD = $1,481), respectively.
      CONCLUSIONS: Hospitalizations and possible exacerbations among patients with IPF
      were costly. Appropriate management of IPF needs to be considered to help slow
      IPF disease progression. DISCLOSURES: Boehringer Ingelheim Pharmaceuticals, Inc.
      (BIPI) provided funding for this study. Yu and Devercelli are currently salaried
      employees of BIPI. Wu, Chuang, Wang, Pan, and Benjamin are currently employees of
      Evidera, which provides consulting and other research services to pharmaceutical,
      device, government, and nongovernment organizations. In their salaried positions,
      they work with a variety of companies and organizations and are precluded from
      receiving payment or honoraria directly from these organizations for services
      rendered. Evidera received funding from BIPI to conduct the analysis. Coultas was
      previously a paid consultant of BIPI. The contents do not represent the views of
      the Department of Veterans Affairs or the U.S. government. This manuscript does
      not contain clinical studies or patient data. The authors have full control of
      all primary data, and they agree to allow the journal to review their data if
      requested. All authors meet the criteria for authorship as recommended by the
      International Committee of Medical Journal Editors, and they are fully
      responsible for all content and editorial decisions and were involved at all
      stages of manuscript development. The manuscript was drafted by Benjamin, Wu, and
      Yu and revised by Wang, Pan, Yu, Coultas, and Devercelli. The study was designed
      by Yu, Wu, Chuang, Wang, Benjamin, and Coultas. Statistical analysis was
      conducted by Wu, Chuang, and Wang. Senior review was provided by Coultas and
      Devercelli.

PMID- 27023696
TI  - AMCP Partnership Forum: Driving New Advances in Dyslipidemia Management.
AB  - Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors are specialty
      medications approved for the treatment of dyslipidemia. Because dyslipidemia is a
      prevalent and chronic condition, the costs associated with PCSK9 inhibitors must
      be carefully weighed against the benefits that they provide. However, the long
      term clinical benefits of these agents are not yet fully defined, creating a
      complex situation for third-party payers who must determine how to allocate
      limited resources. To engage national stakeholders in a discussion of how to
      wisely use PCSK9 inhibitors in health care, the Academy of Managed Care Pharmacy
      organized a forum in Washington, DC, on September 16, 2015. The forum began with
      presentations reviewing the current environment for dyslipidemia treatment.
      Following these presentations, participants engaged in discussions regarding how
      to best select patients for treatment based on current treatment guidelines, how
      managed care pharmacy can best manage high-cost specialty products that may be
      indicated for large numbers of patients, and how managed care organizations can
      use real-world evidence to assess the impact of evolving treatment guidelines and
      options. Participants called for the development of a national database to gather
      more meaningful data regarding the impact of PCSK9 inhibitors on clinical
      outcomes. Such a database would be invaluable for determining the real-world
      impact of specialty medications and would support the development of sensible
      third-party payer benefit structures, coverage decisions, medical policies, and
      risk-sharing contracts. In the meantime, participants recommended enhanced
      collaboration among stakeholders for improved information sharing, increased
      collection and evaluation of real-world evidence, use of available cost
      effectiveness analyses, and the implementation of strategies that optimize the
      use of evidence-based therapies. DISCLOSURES: The AMCP Partnership Forum on
      Driving New Advances in Dyslipidemia Management and the development of this
      proceedings document was supported by Lilly USA, MedImpact Healthcare Systems,
      Merck & Co., PerformRx, Pfizer, and Sanofi.

PMID- 27023697
TI  - AMCP Partnership Forum: Biosimilars--Ready, Set, Launch.
AB  - Through 2020, reference biologic products will lose patent protection that will
      be worth $54 billion to the U.S. economy. Consequently, interest in biosimilars
      is intensifying across the health care industry. Managed care organizations
      (MCOs) are depending on the savings opportunity that bio-similars promise. After
      the first FDA approval of a biosimilar in March 2015, the Academy of Managed Care
      Pharmacy (AMCP) convened a biosimilar Partnership Forum on June 10-11, 2015. The
      goal of this forum was to address current readiness of MCOs to optimize
      biosimilars; identify gaps, challenges, and opportunities with regard to
      biosimilars; and recommend education and training content to help AMCP best meet
      the needs of its members and stakeholders. The forum brought together multiple
      stakeholders from MCOs, pharmacy benefit managers, specialty pharmacies,
      integrated delivery networks, federal government and standards setting
      organizations, consumer advocacy groups, and the pharmaceutical industry. Through
      a series of 4 one-hour webinars and a 1.5-day live workgroup session,
      participants identified current challenges and readiness issues in addressing
      biosimilars. These challenges included lack of a consolidated educational
      strategy for incorporating biosimilars into the clinical decision-making process;
      deficiencies in current levels of federal (e.g., the FDA) or state (e.g.,
      departments of insurance) guidance; limited intelligence on pricing strategies
      and consideration of stakeholder contracting alignment and risk sharing; and
      operational implementation issues. Participants identified necessary tactics for
      executing a successful bio-similar strategy. These tactics included creating a
      broad multiple stakeholder coalition to support educational efforts to gain
      public, provider, and other stakeholder acceptance; aligning utilization
      incentives through reimbursement policies and programs; encouraging benefit
      design and stakeholder collaboration; advancing the coding and technology
      infrastructure to support operations, contracting, billing, reimbursement, and
      reporting needs; and having appropriate active surveillance mechanisms to enable
      assessment of the clinical performance of biosimilars and their innovator
      products. Participants recommended guidance for AMCP to optimally support its
      membership and stakeholders with educational and training programs at multiple
      venues; a platform for regular communications and updates; and advocacy,
      community promotion, and education. DISCLOSURES: The AMCP Partnership Forum
      entitled "Biosimilars-Ready, Set, Launch" and the development of this report were
      supported by Abbvie, Amgen, Apotex, Boehringer, Merck, Momenta, and Sandoz.

PMID- 27023698
TI  - Surgical site infection following cesarean deliveries: trends and risk factors.
AB  - OBJECTIVE: To identify trends and risk factors for early surgical site infection
      (SSI) following cesarean delivery (CD). METHODS: A population-based study
      comparing characteristics of women who have and have not developed post cesarean
      SSI was conducted. Deliveries occurred between the years 1988 and 2013 in a
      tertiary medical center. A multivariable logistic regression model, with
      backwards elimination, was used to control for confounders. RESULTS: Of the 41
      375 cesarean deliveries performed during the study period, 1521 (3.7%) were
      complicated with SSI. SSI rates significantly deceased over the years, from 7.4%
      in 1988 to 1.5% in 2012. Using a multivariable regression model, the following
      independent risk factors for SSI were identified: obesity (OR 2.0; 95% CI, 1.6
      2.5); previous CD (OR 1.8; 95% CI, 1.6-2.0); hypertensive disorders (OR 1.4; 95%
      CI, 1.2-1.6); premature rupture of membranes (OR 1.3; 95% CI, 1.1-1.6);
      gestational diabetes mellitus (GDM, OR 1.2; 95% CI, 1.1-1.4); and recurrent
      pregnancy losses (OR 1.2; 95% CI, 1.1-1.5). CONCLUSION: Independent risk factors
      for post-cesarean SSI include obesity, GDM, hypertensive disorders of pregnancy,
      premature rupture of membranes, and recurrent pregnancy losses. Information
      regarding higher rates of SSI and preventative measures should be provided to
      these high-risk women prior to surgery.

PMID- 27023699
TI  - Amphixenosic Aspects of Staphylococcus aureus Infection in Man and Animals.
AB  - According to the mode of transmission, Staphylococcus aureus infection between
      hosts is classified as "direct zoonoses," or infection that is transmitted from
      an infected vertebrate host to a susceptible host (man) by direct contact, by
      contact with a fomite or by a mechanical vector. The agent itself undergoes
      little or no propagative or developmental changes during transmission. According
      to the reservoir host, staphylococcosis is most precisely defined as
      "zooanthroponoses" or infections transmitted from man to lower vertebrate animals
      (e.g., streptococci, diphtheria, Enterobacteriaceae, human tuberculosis in cattle
      and parrots), but also "anthropozoonoses" or infections transmitted to man from
      lower vertebrate animals. In particular, actually, the correct definition of S.
      aureus infections between humans and animals is "amphixenoses" or infections
      maintained in both man and lower vertebrate animals and transmitted in either
      direction. S. aureus exhibits tropisms to many distinct animal hosts. While
      spillover events can occur wherever there is an interface between host species,
      changes in host tropism only occur with the establishment of sustained
      transmission in the new host species, leading to clonal expansion. Although the
      genomic variation underpinning adaptation in S. aureus genotypes infecting bovids
      and poultry has been well characterized, the frequency of switches from one host
      to another remains obscure. In this review, we sought to identify the sustained
      switches in host tropism in the S. aureus population, both anthroponotic and
      zoonotic, and their distribution over the species phylogeny. S. aureus is an
      organism with the capacity to switch into and adapt to novel hosts, even after
      long periods of isolation in a single host species. Based on this evidence,
      animal-adapted S. aureus lineages exhibiting resistance to antibiotics must be
      considered a major threat to public health, as they can adapt to the human
      population.

PMID- 27023700
TI  - Fish mouths as engineering structures for vortical cross-step filtration.
AB  - Suspension-feeding fishes such as goldfish and whale sharks retain prey without
      clogging their oral filters, whereas clogging is a major expense in industrial
      crossflow filtration of beer, dairy foods and biotechnology products. Fishes'
      abilities to retain particles that are smaller than the pore size of the gill
      raker filter, including extraction of particles despite large holes in the
      filter, also remain unexplained. Here we show that unexplored combinations of
      engineering structures (backward-facing steps forming d-type ribs on the porous
      surface of a cone) cause fluid dynamic phenomena distinct from current biological
      and industrial filter operations. This vortical cross-step filtration model
      prevents clogging and explains the transport of tiny concentrated particles to
      the oesophagus using a hydrodynamic tongue. Mass transfer caused by vortices
      along d-type ribs in crossflow is applicable to filter-feeding duck beak lamellae
      and whale baleen plates, as well as the fluid mechanics of ventilation at fish
      gill filaments. 

PMID- 27023702
TI  - Manganese Toxicity in Sugarcane Plantlets Grown on Acidic Soils of Southern
      China.
AB  - Ratoon sugarcane plantlets in southern China have suffered a serious chlorosis
      problem in recent years. To reveal the causes of chlorosis, plant nutrition in
      chlorotic sugarcane plantlets and the role of manganese (Mn) in this condition
      were investigated. The study results showed that the pH of soils growing
      chlorotic plantlets ranged from 3.74 to 4.84. The symptoms of chlorosis were
      similar to those of iron (Fe) deficiency while the chlorotic and non-chlorotic
      plantlets contained similar amount of Fe. Chlorotic plantlets had 6.4-times more
      Mn in their leaf tissues compared to the control plants. There was a
      significantly positive correlation between Mn concentration in the leaves and the
      exchangeable Mn concentration in the soils. Moreover, leaf Mn concentration was
      related to both seasonal changes in leaf chlorophyll concentration and to the
      occurrence of chlorosis. Basal stalks of mature sugarcanes contained up to 564.36
      mg.kg(-1) DW Mn. Excess Mn in the parent stalks resulted in a depress of
      chlorophyll concentration in the leaves of sugarcanes as indicated by lower
      chlorophyll concentration in the leaves of plantlets emerged from basal stalks.
      Ratoon sugarcane plantlets were susceptible to chlorosis due to high Mn
      accumulation in their leaves (456.90-1626.95 mg.kg(-1) DW), while in planted
      canes chlorosis did not occur because of low Mn accumulation (94.64-313.41mg.kg(
      1) DW). On the other hand, active Fe content in chlorotic plantlets (3.39 mg kg(
      1) FW) was only equivalent to 28.2% of the concentration found in the control.
      These results indicate that chlorosis in ratoon sugarcane plantlets results from
      excessive Mn accumulated in parent stalks of planted cane sugarcanes grown on
      excessive Mn acidic soils, while active Fe deficiency in plantlets may play a
      secondary role in the chlorosis.

PMID- 27023701
TI  - Role of Nutrition and Muscle in Cirrhosis.
AB  - OPINION STATEMENT: Most widely recognized complications in cirrhotic patients
      include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction,
      and hepatocellular carcinoma; however, malnutrition and muscle wasting
      (sarcopenia) constitute common complications which negatively impact survival,
      quality of life, and response to stressors, such as infection and surgery in
      patients with cirrhosis. Despite the important role that malnutrition and
      sarcopenia play in the prognosis of patients with cirrhosis, they are frequently
      overlooked, in part because nutritional assessment can be a difficult task in
      patients with cirrhosis due to fluid retention and/or overweight. Moreover,
      patients with cirrhosis may develop simultaneous loss of skeletal muscle and gain
      of adipose tissue, culminating in the condition of "sarcopenic obesity." In
      addition, muscle depletion is characterized by both a reduction in muscle size
      and increased proportion of intermuscular and intramuscular fat-denominated
      "myosteatosis." Sarcopenia in cirrhotic patients has been associated with
      increased mortality, sepsis complications, hyperammonemia, overt hepatic
      encephalopathy, and increased length of stay after liver transplantation.
      Muscularity assessment with cross-sectional imaging studies has become an
      attractive index of nutritional status evaluation in cirrhosis, as sarcopenia
      reflects a chronic detriment in general physical condition, rather than acute
      severity of the liver disease. In this review, we discuss the current diagnostic
      methods to evaluate malnutrition and muscle abnormalities in cirrhosis and also
      analyze the current knowledge regarding incidence and clinical impact of
      malnutrition and muscle abnormalities in cirrhosis and their impact after liver
      transplantation. We also discuss existing and potential novel therapeutic
      strategies for malnutrition in cirrhosis, emphasizing the recognition of
      sarcopenia in cirrhosis in an effort to improve survival and reduce morbidity
      related to cirrhosis. Finally, we analyze new studies including sarcopenia with
      the MELD score that seems to allow better prediction of mortality among cirrhotic
      patients waiting for liver transplantation.

PMID- 27023703
TI  - New Findings in Diabetic Maculopathy and Proliferative Disease by Swept-Source
      Optical Coherence Tomography Angiography.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) angiography (OCTA)
      features of diabetic retinopathy. METHODS: Retrospective serial case reports were
      examined of patients who underwent routine clinical examination and OCTA with
      both DRI OCT Atlantis prototype and Triton Swept-Source OCT of the posterior pole
      and mid-periphery. When considered necessary, fluorescein fundus angiography
      (FFA) with OPTOS California wide-field imaging was performed. The findings were
      compared with the current literature. RESULTS: Forty-three consecutive patients
      (86 eyes) were evaluated. Fourteen of these patients (28 eyes) underwent an
      additional FFA examination due to advanced retinopathy signs, such as diabetic
      macular edema, ischemia or neovascularization (NV). OCTA was able to detect the
      microvascular lesions observed on color fundus images in the whole sample. Thirty
      six of the 86 eyes showed foveal avascular zone enlargement on OCTA.
      Microvascular lesions, diabetic macular edema, and NV of the optic disc observed
      on FFA were also detected on OCTA in all cases (28/28 eyes). Features of NV
      elsewhere were detected on FFA in 16/28 eyes. Ten of the 16 eyes had signs of NV
      within the 100 central degrees, and OCTA was able to detect these signs in 9 of
      the eyes. CONCLUSION: OCTA is an effective noninvasive imaging technique that can
      provide additional information regarding the localization and morphology of
      vascular lesions in all cases of NV of the optic disc and in more than half of
      cases of NV elsewhere, suggesting that it is a noninferior technique for the
      study of posterior pole alterations compared with FFA, which remains the gold
      standard and is fundamental for the study of the retinal periphery.

PMID- 27023704
TI  - Three-Dimensional Reconstruction of Three-Way FRET Microscopy Improves Imaging of
      Multiple Protein-Protein Interactions.
AB  - Fluorescence resonance energy transfer (FRET) microscopy is a powerful tool for
      imaging the interactions between fluorescently tagged proteins in two-dimensions.
      For FRET microscopy to reach its full potential, it must be able to image more
      than one pair of interacting molecules and image degradation from out-of-focus
      light must be reduced. Here we extend our previous work on the application of
      maximum likelihood methods to the 3-dimensional reconstruction of 3-way FRET
      interactions within cells. We validated the new method (3D-3Way FRET) by
      simulation and fluorescent protein test constructs expressed in cells. In
      addition, we improved the computational methods to create a 2-log reduction in
      computation time over our previous method (3DFSR). We applied 3D-3Way FRET to
      image the 3D subcellular distributions of HIV Gag assembly. Gag fused to three
      different FPs (CFP, YFP, and RFP), assembled into viral-like particles and
      created punctate FRET signals that become visible on the cell surface when 3D
      3Way FRET was applied to the data. Control experiments in which YFP-Gag, RFP-Gag
      and free CFP were expressed, demonstrated localized FRET between YFP and RFP at
      sites of viral assembly that were not associated with CFP. 3D-3Way FRET provides
      the first approach for quantifying multiple FRET interactions while improving the
      3D resolution of FRET microscopy data without introducing bias into the
      reconstructed estimates. This method should allow improvement of widefield,
      confocal and superresolution FRET microscopy data. 

PMID- 27023705
TI  - Tbo-Filgrastim: A Review in Neutropenic Conditions.
AB  - Tbo-filgrastim (filgrastim XM02; Biograstim((r)), Ratiograstim((r)),
      Tevagrastim((r))) is approved in the EU as a biosimilar of filgrastim
      (Neupogen((r))) for use in all indications for which reference filgrastim is
      approved, including chemotherapy-induced neutropenia, neutropenia in patients
      undergoing myeloablative therapy followed by bone marrow transplantation,
      mobilization of peripheral blood stem cells (PBSCs), severe chronic neutropenia,
      and neutropenia in HIV infection. Tbo-filgrastim (Granix((r))) is also approved
      as a biologic in the USA for neutropenia associated with chemotherapy. Tbo
      filgrastim has demonstrated bioequivalence to reference filgrastim in terms of
      its pharmacokinetic and pharmacodynamic profiles. In phase III trials, tbo
      filgrastim was equivalent to reference filgrastim in ameliorating severe
      neutropenia in patients receiving chemotherapy for breast cancer, lung cancer, or
      non-Hodgkin lymphoma. In addition, the efficacy of tbo-filgrastim for PBSC
      mobilization in the allogeneic and autologous settings has been demonstrated in
      several small studies. Tbo-filgrastim was generally well tolerated, with a
      similar safety profile to that of reference filgrastim. Most adverse events were
      of mild or moderate severity. Biosimilars such as tbo-filgrastim have the
      potential to reduce healthcare costs compared with those of reference filgrastim;
      this may provide patients with more cost-effective treatment options. Current
      evidence indicates that tbo-filgrastim is a useful alternative to reference
      filgrastim in patients requiring filgrastim therapy for various neutropenic
      conditions.

PMID- 27023706
TI  - Future Therapeutics in Alzheimer's Disease: Development Status of BACE
      Inhibitors.
AB  - Alzheimer's disease (AD) is the primary cause of dementia in the elderly. It
      remains incurable and poses a huge socio-economic challenge for developed
      countries with an aging population. AD manifests by progressive decline in
      cognitive functions and alterations in behaviour, which are the result of the
      extensive degeneration of brain neurons. The AD pathogenic mechanism involves the
      accumulation of amyloid beta peptide (Abeta), an aggregating protein fragment
      that self-associates to form neurotoxic fibrils that trigger a cascade of
      cellular events leading to neuronal injury and death. Researchers from academia
      and the pharmaceutical industry have pursued a rational approach to AD drug
      discovery and targeted the amyloid cascade. Schemes have been devised to prevent
      the overproduction and accumulation of Abeta in the brain. The extensive efforts
      of the past 20 years have been translated into bringing new drugs to advanced
      clinical trials. The most progressed mechanism-based therapies to date consist of
      immunological interventions to clear Abeta oligomers, and pharmacological drugs
      to inhibit the secretase enzymes that produce Abeta, namely beta-site amyloid
      precursor-cleaving enzyme (BACE) and gamma-secretase. After giving an update on
      the development and current status of new AD therapeutics, this review will focus
      on BACE inhibitors and, in particular, will discuss the prospects of verubecestat
      (MK-8931), which has reached phase III clinical trials. 

PMID- 27023707
TI  - [Supernumerary teeth in the maxilla and mandible-an interdisciplinary challenge.
      Part 2: diagnostic pathways and current therapeutic concepts].
AB  - Proper localization of supernumerary teeth is very important for the diagnosis,
      treatment planning, and prior to any surgical intervention. Traditionally,
      supernumerary teeth were diagnosed and located using two-dimensional (2D)
      radiographic methods such as panoramic views, cephalometric imaging, and also
      intraoral (also often occlusal) radiographs. With the introduction of cone beam
      computed tomography (CBCT) in dental medicine, this three-dimensional (3D)
      imaging technique is now more and more used for the exact localisation of
      supernumerary teeth and the diagnosis of root resorption of adjacent teeth.
      Treatment planning depends on various factors such as the time of diagnosis, the
      age of the patient, the position of the supernumerary tooth and possible
      complications. In the present second part of this review article on supernumerary
      teeth in the maxilla and mandible, the diagnostic workflow and current treatment
      concepts will be presented and critically discussed. 

PMID- 27023708
TI  - Social/economic costs and health-related quality of life in patients with rare
      diseases in Europe.

PMID- 27023709
TI  - Expression, purification, and crystallization of Schizosaccharomyces pombe eIF2B.
AB  - Tight control of protein synthesis is necessary for cells to respond and adapt to
      environmental changes rapidly. Eukaryotic translation initiation factor (eIF) 2B,
      the guanine nucleotide exchange factor for eIF2, is a key target of translation
      control at the initiation step. The nucleotide exchange activity of eIF2B is
      inhibited by the stress-induced phosphorylation of eIF2. As a result, the level
      of active GTP-bound eIF2 is lowered, and protein synthesis is attenuated. eIF2B
      is a large multi-subunit complex composed of five different subunits, and all
      five of the subunits are the gene products responsible for the neurodegenerative
      disease, leukoencephalopathy with vanishing white matter. However, the overall
      structure of eIF2B has remained unresolved, due to the difficulty in preparing a
      sufficient amount of the eIF2B complex. To overcome this problem, we established
      the recombinant expression and purification method for eIF2B from the fission
      yeast Schizosaccharomyces pombe. All five of the eIF2B subunits were co-expressed
      and reconstructed into the complex in Escherichia coli cells. The complex was
      successfully purified with a high yield. This recombinant eIF2B complex contains
      each subunit in an equimolar ratio, and the size exclusion chromatography
      analysis suggests it forms a heterodecamer, consistent with recent reports. This
      eIF2B increased protein synthesis in the reconstituted in vitro human translation
      system. In addition, disease-linked mutations led to subunit dissociation.
      Furthermore, we crystallized this functional recombinant eIF2B, and the crystals
      diffracted to 3.0 A resolution. 

PMID- 27023711
TI  - High-Yield Production of Boron Nitride Nanosheets and Its Uses as a Catalyst
      Support for Hydrogenation of Nitroaromatics.
AB  - Single- or few-layered h-BN nanosheets (BNNSs) are analogous to graphene and
      possess unique properties. However, their technological applications were
      severely hindered by the low production efficiency of BNNSs. We reported here a
      study in which BNNSs were efficiently produced by exfoliating bulk h-BN powder in
      thionyl chloride without using any dispersion agents. The BNNSs yield was as high
      as 20%, and it could be doubled through the second round of exfoliation of the h
      BN precipitate. Microscopic results revealed that the BNNSs generally consisted
      of 3-20 layers. Pd nanoparticles were successfully immobilized and uniformly
      distributed on BNNS surfaces through the deposition-precipitation method. The
      resultant Pd-BNNS catalyst exhibited high catalytic activity and recyclability
      for the hydrogenation of nitro aromatics, demonstrating that BNNSs served as a
      promising platform to fabricate heterogeneous catalysts. 

PMID- 27023710
TI  - Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived
      Cell Migration.
AB  - A single layer of epicardial cells lines the heart, providing paracrine factors
      that stimulate cardiomyocyte proliferation and directly contributing
      cardiovascular progenitors during development and disease. While a number of
      factors have been implicated in epicardium-derived cell (EPDC) mobilization, the
      mechanisms governing their subsequent migration and differentiation are poorly
      understood. Here, we present in vitro and ex vivo strategies to study EPDC
      motility and differentiation. First, we describe a method of obtaining primary
      epicardial cells by outgrowth culture from the embryonic mouse heart. We also
      introduce a detailed protocol to assess three-dimensional migration of labeled
      EPDC in an organ culture system. We provide evidence using these techniques that
      genetic deletion of myocardin-related transcription factors in the epicardium
      attenuates EPDC migration. This approach serves as a platform to evaluate
      candidate modifiers of EPDC biology and could be used to develop genetic or
      chemical screens to identify novel regulators of EPDC mobilization that might be
      useful for cardiac repair. 

PMID- 27023712
TI  - Challenges in the treatment of hormone receptor-positive, HER2-negative
      metastatic breast cancer with brain metastases.
AB  - Brain metastases are a major cause of morbidity and mortality for women with
      hormone receptor (HR)-positive breast cancer, yet little is known about the
      optimal treatment of brain disease in this group of patients. Although these
      patients are at lower risk for brain metastases relative to those with HER2
      positive and triple-negative disease, they comprise the majority of women
      diagnosed with breast cancer. Surgery and radiation continue to have a role in
      the treatment of brain metastases, but there is a dearth of effective systemic
      therapies due to the poor penetrability of many systemic drugs across the blood
      brain barrier (BBB). Additionally, patients with brain metastases have long been
      excluded from clinical trials, and few studies have been conducted to evaluate
      the safety and effectiveness of systemic therapies specifically for the treatment
      of HER2-negative breast cancer brain metastases. New approaches are on the
      horizon, such as nanoparticle-based cytotoxic drugs that have the potential to
      cross the BBB and provide clinically meaningful benefits to patients with this
      life-threatening consequence of HR-positive breast cancer. 

PMID- 27023713
TI  - Stone volume is best predictor of operative time required in retrograde
      intrarenal surgery for renal calculi: implications for surgical planning and
      quality improvement.
AB  - Retrograde intrarenal surgery (RIRS) is highly successful at eliminating renal
      stones of various sizes and compositions. As urologists are taking on more
      complex procedures using RIRS, this has led to an increase in operative (OR)
      times. Our objective was to determine the best predictor of OR time in patients
      undergoing RIRS. We retrospectively reviewed the records of patients undergoing
      unilateral RIRS for solitary stones over a 10 year time span. Stones were
      fragmented and actively extracted using a basket. Variables potentially affecting
      OR time such as patient age, sex, BMI, lower pole stone location, volume,
      Hounsfield units (HU), composition, ureteral access sheath (UAS) use, and pre
      operative stenting were collected. Multivariable linear and stepwise regression
      was used to evaluate the predictors of OR time. There were 118 patients that met
      inclusion criteria. The median stone volume was 282.6 mm3 (IQR 150.7-644.7) and
      the mean OR time was 50 min (+/-25.9 SD). On univariate linear regression, stone
      volume had a moderate correlation with OR time (y = 0.022x + 38.2, r 2 = 0.363, p
      < 0.01). On multivariable stepwise regression, stone volume had the strongest
      impact on OR time, increasing time by 2.0 min for each 100 mm3 increase in stone
      volume (p < 0.001). UAS added 13.5 (SE 3.9, p = 0.001) minutes and renal lower
      pole location added 9 min (SE 4.3, p = 0.03) in each case they were used. Pre
      operative stenting, HU, calcium oxalate stone composition, sex, and age had no
      significant effect on OR time. Amongst the main stone factors in RIRS, stone
      volume has the strongest impact on operative time. This can be used to predict
      the length of the procedure by roughly adding 2 min per 100 mm3 increase in stone
      volume.

PMID- 27023714
TI  - Increased renal papillary density in kidney stone formers detectable by CT scan
      is a potential marker of stone risk, but is unrelated to underlying
      hypercalciuria.
AB  - Several previous studies have reported an increase in Hounsfield unit density of
      the renal papillae in patients with nephrolithiasis compared with controls.
      Kidney stone formers (KSF) were found to have higher papillary and cortical
      density in both kidneys, irrespective of which side had calculi, and it was
      proposed that this might be related to the presence of underlying hypercalciuria.
      The current study was designed: (1) to determine whether recurrent KSF do have
      higher papillary density compared with healthy controls; (2) to test an
      association between higher renal papillary density and the presence of
      hypercalciuria in KSF. This retrospective case-matched controlled study was
      carried out at the Royal Free Hospital, London, UK. We investigated 111 patients,
      57 of whom were KSF and 54 healthy controls. The CT attenuation values were
      measured within a 0.2 cm(2) area of the renal papilla in the upper, middle, and
      lower segments of each kidney, and were compared between KSF and non-stone
      formers, and between KSF with and without hypercalciuria. There were no
      significant differences in age and sex between groups. Papillary density was
      significantly higher in KSF by both crude and adjusted analyses (p < 0.001).
      However, there was no association between higher papillary density and
      hypercalciuria in KSF. The papillary density measured by CT is a useful, non
      invasive tool to differentiate between KSF and healthy controls. The absence of
      any correlation between papillary density and hypercalciuria suggests that the
      presence of clinically significant underlying renal stone disease, rather than
      urinary metabolic abnormalities, correlates with radiologically detectable
      increased papillary density. 

PMID- 27023715
TI  - Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some
      anesthetic drugs in the hippocampal area of rats.
AB  - The present study was designed to evaluate the antioxidant effects of oleuropein
      against oxidative stress in the hippocampal area of rats. We used seven
      experimental groups as follows: Control, Propofol, Propofol-Ketamine (Pro.-Ket.),
      Xylazine-Ketamine (Xyl.-Ket.), and three oleuropein-pretreated groups (Ole.-Pro.,
      Ole.-Pro.-Ket. and Ole.-Xyl.-Ket.). The oleuropein-pretreated groups received
      oleuropein (15 mg/kg body weight as orally) for 10 consecutive days. Propofol 100
      mg/kg, xylazine 3 mg/kg, and ketamine 75 mg/kg once as ip was used on the 11th
      day of treatment. Spatial memory impairment and antioxidant status of hippocampus
      were measured via Morris water maze, lipid peroxidation marker, and antioxidant
      enzyme activities. Spatial memory impairment and lipid peroxidation significantly
      increased in Xyl.-Ket.-treated rats in comparison to the control, propofol, Ole.
      Pro. and Ole.-Pro.-Ket. groups. Oleuropein pretreatment significantly reversed
      spatial memory impairment and lipid peroxidation in the Ole.-Xyl.-Ket. group as
      compared to the Xyl.-Ket.-treated rats. There was no significant difference
      between the control and the propofol group in lipid peroxidation and spatial
      memory status. Superoxide dismutase and catalase activities both significantly
      decreased in Xyl.-Ket.-treated rats when compared to the control, propofol, Ole.
      Pro., Ole.-Pro.-Ket., and Ole.-Xyl.-Ket. groups. In contrast, glutathione
      peroxidase activity in Xyl.-Ket.-treated rats significantly increased as compared
      to the control, propofol, Pro.-Ket., Ole.-Pro., and Ole.-Pro.-Ket. groups. We
      concluded that xylazine in combination with ketamine is an oxidative anesthetic
      drug and oleuropein pretreatment attenuates cognitive dysfunction and oxidative
      stress induced by anesthesia in the hippocampal area of rats. We also confirmed
      the antioxidant properties of propofol as a promising antioxidant anesthetic
      agent.

PMID- 27023717
TI  - Evaluation of LRINEC Scale Feasibility for Predicting Outcomes of Fournier
      Gangrene.
AB  - BACKGROUND: Fournier gangrene (FG) is a fulminant necrotizing infection of the
      perineal, perianal, and periurethral tissues. The Laboratory Risk Indicator for
      Necrotizing Fasciitis (LRINEC) scale is used for diagnosis of necrotizing
      fasciitis. However, data on its relevance and usefulness in FG are lacking. The
      aim of this study was to evaluate the utility of the LRINEC scale in predicting
      the outcome of FG. METHODS: This retrospective case study included 41 patents
      with FG treated at our institution from 2000 to 2013. The patients were divided
      into survivors and non-survivors. RESULTS: The mortality rate was 22%. The median
      age (75 vs. 62.5 y; p = 0.013), rate of co-existing diabetes mellitus (66.7% vs.
      3.1%; p < 0.001), and median affected skin surface (4% vs. 1%; p < 0.001) were
      greater in the non-survivors. Seven of nine patients (77.8%) who did not survive
      (compared with 37.5% who survived) had a polymicrobial infection (p = 0.032). Of
      all the causative pathogens isolated, Proteus mirabilis was more common in non
      survivors (55.6% vs. 6.3%; p = 0.001). The median calculated LRINEC score for
      survivors was 5 compared with 10 for the non-survivors (p < 0.001). Regression
      analysis showed that all the aforementioned variables, except for polymicrobial
      culture, were significant risk factors for predicting death. The area under the
      receiver operating characteristic curve for the LRINEC score was the highest,
      0.976 (95% confidence interval 0.872-0.999; p < 0.0001), and the cut-off value
      was >=9 with 93.7% specificity and 100% susceptibility for the prediction of a
      lethal outcome. CONCLUSIONS: The LRINEC score could be used for prediction of
      disease severity and outcomes. A threshold of 9 could be a high-value predictor
      of death during the initial evaluation of patients with FG.

PMID- 27023716
TI  - Recent advances in basic research on the trigeminal ganglion.
AB  - Peripheral tissue inflammation can alter the properties of somatic sensory
      pathways, causing behavioral hypersensitivity and resulting in increased
      responses to pain caused by noxious stimulation (hyperalgesia) and normally
      innocuous stimulation (allodynia). These hypersensitivities for nociception are
      caused by changes in the excitability of trigeminal ganglion (TG) neurons. These
      changes alter sensory information processing in the neurons in the medullary
      trigeminal nucleus of caudalis. Increasing information is becoming available
      regarding trigeminal neuron-neuron/neuron-satellite glial cells (SGCs)
      communication. The activation of intraganglionic communication plays an important
      role in the creation and maintenance of trigeminal pathological pain. Therefore,
      in this review, we focus on the recent findings for sensory functions and
      pharmacological modulation of TG neurons and SGCs under normal and pathological
      conditions, and we discuss potential therapeutic targets in glia-neuronal
      interactions for the prevention of trigeminal neuropathic and inflammatory pain. 

PMID- 27023718
TI  - Thermal Decomposition of 3-Bromopropene. A Theoretical Kinetic Investigation.
AB  - A detailed kinetic study of the gas-phase thermal decomposition of 3-bromopropene
      over wide temperature and pressure ranges was performed. Quantum chemical
      calculations employing the density functional theory methods B3LYP, BMK, and M06
      2X and the CBS-QB3 and G4 ab initio composite models provide the relevant part of
      the potential energy surfaces and the molecular properties of the species
      involved in the CH2?CH-CH2Br -> CH2?C?CH2 + HBr (1) and CH2?CH-CH2Br -> CH2?CH
      CH2 + Br (2) reaction channels. Transition-state theory and unimolecular reaction
      rate theory calculations show that the simple bond fission reaction ( 2 ) is the
      predominant decomposition channel and that all reported experimental studies are
      very close to the high-pressure limit of this process. Over the 500-1400 K range
      a rate constant for the primary dissociation of k2,infinity = 4.8 * 10(14) exp(
      55.0 kcal mol(-1)/RT) s(-1) is predicted at the G4 level. The calculated
      k1,infinity values lie between 50 to 260 times smaller. A value of 10.6 +/- 1.5
      kcal mol(-1) for the standard enthalpy of formation of 3-bromopropene at 298 K
      was estimated from G4 thermochemical calculations. 

PMID- 27023719
TI  - Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age
      Related Macular Degeneration.
AB  - Age-related macular degeneration continues to be the leading cause of severe
      central vision loss in older adults of European descent. Optical coherence
      tomography angiography (OCT-A) enables more accurate identification of type 1
      neovascularization in age-related macular degeneration than traditional
      fluorescein and indocyanine green angiographies. In addition, OCT-A facilitates
      the morphological classification of type 1 lesions, including features
      characteristic of early, mature, and fibrotic lesions. Vessel complex analysis,
      including lesion area and capillary density quantification, can also be readily
      measured and monitored over time. Performing this analysis following anti
      vascular endothelial growth factor therapy may lead to a better understanding of
      the efficacies and responses to such treatments. Although some limitations
      currently exist, OCT-A is a promising imaging modality that could prove to have
      profound implications if incorporated into regular clinical practice. 

PMID- 27023720
TI  - Changes in the Capillarity of the Rat Extensor Digitorum Longus Muscle 4 Weeks
      after Nerve Injury Studied by 2D Measurement Methods.
AB  - We have previously shown by 3D study that 2 weeks after nerve injury there was no
      change in the length of capillaries per muscle fibre length in rat extensor
      digitorum longus muscle (EDL). The primary goal of the present 2D study was to
      determine the capillarity of rat EDL 4 weeks after various modes of nerve injury.
      Additionally, we wished to calculate the same capillary/fibre parameters that
      were used in our 3D stereological study. EDL muscles derived from denervated (4
      weeks after nerve injury), re-innervated (4 weeks after two successive nerve
      crushes) and age-matched controls from the beginning (CON-1) and the end (CON-2)
      of the experiment were analysed in two ways. Global indices of capillarity, such
      as capillary density (CD) and capillary/fibre (C/F) ratio, were determined by
      automatic analysis, local indices as the number (CAF) and the length of
      capillaries around individual muscle fibres (Lcap) in relation to muscle fibre
      size were estimated manually by tracing the muscle fibre outlines and the
      transversally and longitudinally cut segments of capillaries seen in 5-um-thin
      muscle cross sections. Four weeks after both types of nerve injury, CD increased
      in comparison to the CON-2 group (p < 0.001) due to atrophied muscle fibres in
      denervated muscles and probably proliferation of capillaries in re-innervated
      ones. Higher C/F, CAF (both p < 0.001) and Lcap (p < 0.01) in re-innervated than
      denervated EDL confirmed this assumption. Calculated capillary/fibre parameters
      were comparable to our previous 3D study, which strengthens the practical value
      to the adapted 2D method used in this study. 

PMID- 27023722
TI  - Identification and RNA segment assignment of six structural proteins of Scylla
      serrata reovirus.
AB  - Scylla serrata reovirus (SsRV) is one of the most prevalent viral pathogens of
      the mud crab (S. serrata). The virus represents an unassigned novel genus in the
      Reoviridae family, and contains 12 double-stranded RNA genomic segments. Previous
      analysis of virion proteins concluded that SsRV contains at least eight
      structural proteins, ranging from 25 to 160 kDa. Here, tandem time-of-flight mass
      spectrometry and Western blotting were used to re-identify the structural
      proteins. The results indicate that proteins encoded by SsRV segments S1, S3, S6,
      S9, S11, and S12 are structural proteins. 

PMID- 27023721
TI  - The Roles of Histidines and Charged Residues as Potential Triggers of a
      Conformational Change in the Fusion Loop of Ebola Virus Glycoprotein.
AB  - Ebola virus (EBOV) enters cells from late endosomes/lysosomes under mildly acidic
      conditions. Entry by fusion with the endosomal membrane requires the fusion loop
      (FL, residues 507-560) of the EBOV surface glycoprotein to undergo a pH-dependent
      conformational change. To find the pH trigger for this reaction we mutated
      multiple conserved histidines and charged and uncharged hydrophilic residues in
      the FL and measured their activity by liposome fusion and cell entry of virus
      like particles. The FL location in the membrane was assessed by NMR using soluble
      and lipid-bound paramagnetic relaxation agents. While we could not identify a
      single residue to be alone responsible for pH triggering, we propose that a
      distributed pH effect over multiple residues induces the conformational change
      that enhances membrane insertion and triggers the fusion activity of the EBOV FL.

PMID- 27023723
TI  - Rehabilitation and Pain Management Modalities in Total Knee Arthroplasty.

PMID- 27023724
TI  - Creating Sub-50 Nm Nanofluidic Junctions in PDMS Microfluidic Chip via Self
      Assembly Process of Colloidal Particles.
AB  - Polydimethylsiloxane (PDMS) is the prevailing building material to make
      microfluidic devices due to its ease of molding and bonding as well as its
      transparency. Due to the softness of the PDMS material, however, it is
      challenging to use PDMS for building nanochannels. The channels tend to collapse
      easily during plasma bonding. In this paper, we present an evaporation-driven
      self-assembly method of silica colloidal nanoparticles to create nanofluidic
      junctions with sub-50 nm pores between two microchannels. The pore size as well
      as the surface charge of the nanofluidic junction is tunable simply by changing
      the colloidal silica bead size and surface functionalization outside of the
      assembled microfluidic device in a vial before the self-assembly process. Using
      the self-assembly of nanoparticles with a bead size of 300 nm, 500 nm, and 900
      nm, it was possible to fabricate a porous membrane with a pore size of ~45 nm,
      ~75 nm and ~135 nm, respectively. Under electrical potential, this nanoporous
      membrane initiated ion concentration polarization (ICP) acting as a cation
      selective membrane to concentrate DNA by ~1,700 times within 15 min. This non
      lithographic nanofabrication process opens up a new opportunity to build a
      tunable nanofluidic junction for the study of nanoscale transport processes of
      ions and molecules inside a PDMS microfluidic chip. 

PMID- 27023725
TI  - Air-sampled Filter Analysis for Endotoxins and DNA Content.
AB  - Outdoor aerosol research commonly uses particulate matter sampled on filters.
      This procedure enables various characterizations of the collected particles to be
      performed in parallel. The purpose of the method presented here is to obtain a
      highly accurate and reliable analysis of the endotoxin and DNA content of bio
      aerosols extracted from filters. The extraction of high molecular weight organic
      molecules, such as lipopolysaccharides, from sampled filters involves shaking the
      sample in a pyrogen-free water-based medium. The subsequent analysis is based on
      an enzymatic reaction that can be detected using a turbidimetric measurement. As
      a result of the high organic content on the sampled filters, the extraction of
      DNA from the samples is performed using a commercial DNA extraction kit that was
      originally designed for soils and modified to improve the DNA yield. The
      detection and quantification of specific microbial species using quantitative
      polymerase chain reaction (q-PCR) analysis are described and compared with other
      available methods. 

PMID- 27023726
TI  - Multidrug-resistant bacteria transmitted through high-density EEG in ICU.
AB  - PURPOSE: Prevention of multidrug resistant (MDR) bacterial contamination remains
      a major challenge in ICUs. Many hospital outbreaks involving MDR transmitted
      through environmental contamination have been reported. Bedside high-density EEG
      allow for dynamic cognitive evaluation in brain-injured patients and is used more
      and more frequently in clinical practice to evaluate brain function and predict
      outcome in severely neurologically impaired patients. Unfortunately, the material
      used for this procedure is not entirely disposable. METHOD: We performed a
      systematic analysis of MDR bacterial contamination in patients contaminated in
      our ICU using specific bacteriological methods. RESULTS: We report a proven case
      of cross-contamination of an extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae strain, and a possible case of cross-contamination of a
      carbapenem-resistant Acinetobacter baumannii strain. CONCLUSION: Cross
      contamination of MDR bacteria is possible through high-density EEG material.
      However, appropriate procedures can decrease this risk.

PMID- 27023727
TI  - Fatality associated with propylene glycol poisoning in a cirrhotic patient.

PMID- 27023728
TI  - Multiple myeloma cells modify VEGF/IL-6 levels and osteogenic potential of bone
      marrow stromal cells via Notch/miR-223.
AB  - Bone marrow mesenchymal stromal cells (BMMSCs) represent a crucial component of
      multiple myeloma (MM) microenvironment supporting its progression and
      proliferation. Recently, microRNAs have become an important point of interest for
      research on micro-environmental interactions in MM with some evidence of tumor
      supportive roles in MM. In this study, we examined the role of miR-223 for MM
      support in BMMSCs of 56 patients with MM (MM-BMMSCs). miR-223 expression in MM
      BMMSCs was reduced by the presence of MM cells in vitro in a cell-contact
      dependent manner compared to mono-cultured MM-BMMSCs. Co-cultivation of MM cells
      and MM-BMMSCs induced activation of notch amongst others via jagged-2/notch-2
      leading to increased expression of Hes1, Hey2, or Hes5 in both cell types.
      Cultivation of MM-BMMSCs with increasing levels of recombinant jagged-2 reduced
      miR-223 and increased Hes1 levels in a concentration-dependent manner. Transient
      reduction of miR-223 levels increased VEGF and IL-6 expression and secretion by
      MM-BMMSCs. In addition, reduction of miR-223 degraded the osteogenic
      differentiation potential of MM-BMMSCs. Inhibition of notch signaling induced
      apoptosis in both MM cells and MM-BMMSCs. Furthermore, it increased miR-223
      levels and reduced expression of VEGF and IL-6 by both cell types. These data
      provide first evidence that miR-223 participates in different MM supporting
      pathways in MM-BMMSCs inlcuding regulation of cytokine secretion and expression
      as well as osteogenic differentiation of MM-BMMSCs. More insights on the role of
      miR-223 in MM-BMMSCs and in cellular interactions between MM cells and MM-BMMSCs
      could provide starting points for a more efficient anti-myeloma treatment by
      targeting of notch signaling. (c) 2015 Wiley Periodicals, Inc.

PMID- 27023729
TI  - Phage-mediated Delivery of Targeted sRNA Constructs to Knock Down Gene Expression
      in E. coli.
AB  - RNA-mediated knockdowns are widely used to control gene expression. This
      versatile family of techniques makes use of short RNA (sRNA) that can be
      synthesized with any sequence and designed to complement any gene targeted for
      silencing. Because sRNA constructs can be introduced to many cell types directly
      or using a variety of vectors, gene expression can be repressed in living cells
      without laborious genetic modification. The most common RNA knockdown technology,
      RNA interference (RNAi), makes use of the endogenous RNA-induced silencing
      complex (RISC) to mediate sequence recognition and cleavage of the target mRNA.
      Applications of this technique are therefore limited to RISC-expressing
      organisms, primarily eukaryotes. Recently, a new generation of RNA
      biotechnologists have developed alternative mechanisms for controlling gene
      expression through RNA, and so made possible RNA-mediated gene knockdowns in
      bacteria. Here we describe a method for silencing gene expression in E. coli that
      functionally resembles RNAi. In this system a synthetic phagemid is designed to
      express sRNA, which may designed to target any sequence. The expression construct
      is delivered to a population of E. coli cells with non-lytic M13 phage, after
      which it is able to stably replicate as a plasmid. Antisense recognition and
      silencing of the target mRNA is mediated by the Hfq protein, endogenous to E.
      coli. This protocol includes methods for designing the antisense sRNA,
      constructing the phagemid vector, packaging the phagemid into M13 bacteriophage,
      preparing a live cell population for infection, and performing the infection
      itself. The fluorescent protein mKate2 and the antibiotic resistance gene
      chloramphenicol acetyltransferase (CAT) are targeted to generate representative
      data and to quantify knockdown effectiveness. 

PMID- 27023730
TI  - Human Spinal Motor Control.
AB  - Human studies in the past three decades have provided us with an emerging
      understanding of how cortical and spinal networks collaborate to ensure the vast
      repertoire of human behaviors. Humans have direct cortical connections to spinal
      motoneurons, which bypass spinal interneurons and exert a direct (willful) muscle
      control with the aid of a context-dependent integration of somatosensory and
      visual information at cortical level. However, spinal networks also play an
      important role. Sensory feedback through spinal circuitries is integrated with
      central motor commands and contributes importantly to the muscle activity
      underlying voluntary movements. Regulation of spinal interneurons is used to
      switch between motor states such as locomotion (reciprocal innervation) and
      stance (coactivation pattern). Cortical regulation of presynaptic inhibition of
      sensory afferents may focus the central motor command by opening or closing
      sensory feedback pathways. In the future, human studies of spinal motor control,
      in close collaboration with animal studies on the molecular biology of the spinal
      cord, will continue to document the neural basis for human behavior.

PMID- 27023731
TI  - Ten Years of Grid Cells.
AB  - The medial entorhinal cortex (MEC) creates a neural representation of space
      through a set of functionally dedicated cell types: grid cells, border cells,
      head direction cells, and speed cells. Grid cells, the most abundant functional
      cell type in the MEC, have hexagonally arranged firing fields that tile the
      surface of the environment. These cells were discovered only in 2005, but after
      10 years of investigation, we are beginning to understand how they are organized
      in the MEC network, how their periodic firing fields might be generated, how they
      are shaped by properties of the environment, and how they interact with the rest
      of the MEC network. The aim of this review is to summarize what we know about
      grid cells and point out where our knowledge is still incomplete.

PMID- 27023734
TI  - A swarm of whiteflies--the first record of gregarious behavior from Eocene Baltic
      amber.
AB  - A new whitefly Snotra christelae gen. et sp. n. is characterized, illustrated,
      and described from the Baltic amber. It represents the first record of gregarious
      behavior of Aleyrodinae (Aleyrodidae) whiteflies in fossil state. Implications of
      this finding on interpretation of whiteflies and their host-plant relationships
      and evolutionary traits of the group are discussed. 

PMID- 27023733
TI  - Synthetic mechanobiology: engineering cellular force generation and signaling.
AB  - Mechanobiology seeks to understand and control mechanical and related biophysical
      communication between cells and their surroundings. While experimental efforts in
      this field have traditionally emphasized manipulation of the extracellular force
      environment, a new suite of approaches has recently emerged in which cell
      phenotype and signaling are controlled by directly engineering the cell itself.
      One route is to control cell behavior by modulating gene expression using
      conditional promoters. Alternatively, protein activity can be actuated directly
      using synthetic protein ligands, chemically induced protein dimerization,
      optogenetic strategies, or functionalized magnetic nanoparticles. Proof-of
      principle studies are already demonstrating the translational potential of these
      approaches, and future technological development will permit increasingly precise
      control over cell mechanobiology and improve our understanding of the underlying
      signaling events.

PMID- 27023732
TI  - Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?
AB  - The Cannabis sativa plant has been used to treat various physiological and
      psychiatric conditions for millennia. Current research is focused on isolating
      potentially therapeutic chemical constituents from the plant for use in the
      treatment of many central nervous system disorders. Of particular interest is the
      primary nonpsychoactive constituent cannabidiol (CBD). Unlike Delta(9)
      tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1)
      receptor but has many other receptor targets that may play a role in psychiatric
      disorders. Here we review preclinical and clinical data outlining the therapeutic
      efficacy of CBD for the treatment of motivational disorders such as drug
      addiction, anxiety, and depression. Across studies, findings suggest promising
      treatment effects and potentially overlapping mechanisms of action for CBD in
      these disorders and indicate the need for further systematic investigation of the
      viability of CBD as a psychiatric pharmacotherapy.

PMID- 27023735
TI  - Influence of Perinatal Depression on Labor-Associated Fear and Emotional
      Attachment to the Child in High-Risk Pregnancies and the First Days After
      Delivery.
AB  - BACKGROUND: The aim of this study was to analyze the influence of the level of
      perinatal depression on the labor-associated fear and emotional attachment of
      children born to women during high-risk pregnancies and in the first days after
      delivery. MATERIAL/METHODS: 133 women aged between 16 and 45 years took part in
      the study. The first group included 63 pregnant women (mean age=28.59, SD=5.578)
      with a high-risk pregnancy (of maternal origin, for example, cardiologic
      disorders and diabetes). The second group included 70 women (mean age=27.94,
      SD=5.164) who were in the first days post-partum. Research methods included:
      Analysis of medical documentation; Clinical interview; the Edinburgh Postnatal
      Depression Scale (EPDS); the Questionnaire of Labor-Associated Anxiety (KLP), the
      Maternal-Fetal Attachment Scale (MFAS). RESULTS: Women after delivery displayed a
      higher level of concern for the child's health and life when compared to the high
      risk pregnancy group. The results indicated the appearance of a postnatal fear,
      the level of which is connected with the perception of the role of the mother.
      This fear is lower in women prior to childbirth than it is after. There has also
      been noted a statistically significant relationship between the appearance of
      depression and attachment to the child. Those women with depression show less
      attachment to their child than is the case for those who do not suffer from
      depression. CONCLUSIONS: The appearance of a high level of depression amongst
      women from the high-risk pregnancy group during the first days post childbirth
      was accompanied by perinatal depression and a weaker attachment to the child.

PMID- 27023736
TI  - What infants know about the unsaid: Phonological categorization in the absence of
      auditory input.
AB  - Acquiring a lexicon constitutes an essential step in early language development.
      From an early age on, infants store words with well-specified phonological
      representations, and they can spontaneously activate these representations on the
      basis of visual information only (Mani & Plunkett, 2010a, 2011). To what extent
      can infants inspect and categorize phonological representations in the absence of
      auditory input? The present study focuses on words that infants comprehend but do
      not attempt to pronounce yet, and introduces a novel methodology based on
      anticipatory eye-movements. In two experiments, 21-month-old French-learning
      infants were silently presented with images of familiar objects whose labels they
      comprehended but did not pronounce yet. We tested whether they could activate the
      phonological representation of these labels and categorize them based on their
      length. Infants' performance exceeded chance when the target words were mono- and
      trisyllabic, but not when they were mono- and disyllabic. Thus, even in the
      absence of auditory input infants can activate the phonological representation of
      words they do not pronounce yet, and use this representation to perform a
      categorization based on word length, provided the length difference is
      substantial.

PMID- 27023737
TI  - Delta-opioid receptors as targets for migraine therapy.
AB  - PURPOSE OF REVIEW: The purpose of this review is to contrast the properties of
      the delta-opioid receptor with those of the MU-opioid receptor, which is the
      primary target of most currently available opioid analgesics. We also discuss
      preclinical evidence that indicates the potential efficacy of delta-opioid
      receptor agonists as migraine therapy. RECENT FINDINGS: The use of currently
      available opioid analgesics is highly problematic for patients with migraine.
      Delta-opioid receptors have key differences from MU receptors; these differences
      make the delta receptor an attractive therapeutic target for migraine. Delta
      opioid receptors are expressed in both the peripheral and central nervous system
      in anatomical regions and cell types that are believed to play a role in
      migraine. Delta-receptor agonists have also shown promising effects in multiple
      migraine models, including nitroglycerin evoked hyperalgesia and conditioned
      place aversion, and cortical spreading depression. Evidence from animal models
      indicates that activation of delta receptors is less likely to cause tolerance
      and dependence, and less likely to cause hyperalgesia. In addition, delta
      receptors may have antidepressant and anxiolytic properties that are distinct
      from those of MU receptors. In human studies investigating other conditions,
      delta-receptor agonists have been generally safe and well tolerated. SUMMARY:
      Delta-opioid receptor agonists have promising potential as acute and/or
      preventive migraine therapies, without the problems associated with currently
      used opioid analgesics.

PMID- 27023738
TI  - Vaccine-associated inflammatory diseases of the central nervous system: from
      signals to causation.
AB  - PURPOSE OF REVIEW: As the most cost-effective intervention in preventive medicine
      and as a crucial element of any public health program, vaccination is used
      extensively with over 90% coverage in many countries. As approximately 5-8% of
      the population in developed countries suffer from an autoimmune disorder, people
      with an autoimmune disease are most likely to be exposed to some vaccines before
      or after the disease onset. In fact, a number of inflammatory disorders of the
      central nervous system have been associated with the administration of various
      vaccines. These adverse events, be they spurious associations or genuine
      reactions to the vaccine, may lead to difficulties in obtaining public trust in
      mass vaccination programs. There is, thus, an urgent need to understand whether
      vaccination triggers or enhances autoimmune responses. RECENT FINDINGS: By
      reviewing vaccine-associated inflammatory diseases of the central nervous system,
      this study describes the current knowledge on whether the safety signal was
      coincidental, as in the case of multiple sclerosis with several vaccines, or
      truly reflected a causal link, as in narcolepsy with cataplexy following pandemic
      H1N1 influenza virus vaccination. SUMMARY: The lessons learnt emphasize a central
      role of thorough, ideally prospective, epidemiological studies followed, if the
      signal is deemed plausible or real, by immunological investigations.

PMID- 27023739
TI  - The sensitivity of children with SLI to phonotactic probabilities during lexical
      access.
AB  - The procedural deficit hypothesis (Ullman & Pierpont, 2005) has been proposed to
      account for the combination of linguistic and nonlinguistic deficits observed in
      specific language impairment (SLI). According to this proposal, SLI results from
      a deficit in procedural memory that prevents children from developing sensitivity
      to probabilistic sequences, amongst other deficits. We tested the ability of
      children with SLI to rely on a specific type of probabilities characterizing
      sequences that occur in a given language: phonotactic probabilities. Twenty
      French-speaking children with SLI (M=10;1), 20 typically developing children
      matched for chronological age (M=10;0) and 20 typically developing children
      matched for receptive vocabulary (M=7;4) performed an auditory lexical decision
      task. Pseudoword stimuli were built with combinations of either frequently
      associated phonemes (high phonotactic probability) or infrequently associated
      phonemes (low phonotactic probability). Phonotactic probabilities had a
      significant impact on the accuracy and speed of pseudoword rejection in children
      with SLI, but not in the two control groups. SLI children's greater reliance on
      phonotactic probabilities relative to typically developing children appears to
      contradict the PD hypothesis. Phonotactic probabilities may help them to
      partially overcome their difficulties in developing and accessing the
      phonological lexicon during spoken word recognition. LEARNING OUTCOMES: After
      reading this article, readers will understand the importance of sensitivity to
      phonotactic probabilities in language processing. They will also learn that such
      sensitivity is preserved in children with SLI. Finally, readers will understand
      that children with SLI are more prone to use phonotactic information when
      accessing their lexicon than typically-developing children.

PMID- 27023740
TI  - Epidemiology of Australian Influenza-Related Paediatric Intensive Care Unit
      Admissions, 1997-2013.
AB  - BACKGROUND: Influenza virus predictably causes an annual epidemic resulting in a
      considerable burden of illness in Australia. Children are disproportionately
      affected and can experience severe illness and complications, which occasionally
      result in death. METHODS: We conducted a retrospective descriptive study using
      data collated in the Australian and New Zealand Paediatric Intensive Care
      (ANZPIC) Registry of influenza-related intensive care unit (ICU) admissions over
      a 17-year period (1997-2013, inclusive) in children <16 years old. National
      laboratory-confirmed influenza notifications were used for comparison. RESULTS:
      Between 1997 and 2013, a total of 704 influenza-related ICU admissions were
      recorded, at a rate of 6.2 per 1,000 all-cause ICU admissions. Age at admission
      ranged from 0 days and 15.9 years (median = 2.1 years), with 135 (19.2%) aged <6
      months. Pneumonia/pneumonitis and bronchiolitis were the most common primary
      diagnoses among influenza-related admissions (21.9% and 13.6%, respectively).
      More than half of total cases (59.2%) were previously healthy (no co-morbidities
      recorded), and in the remainder, chronic lung disease (16.7%) and asthma (12.5%)
      were the most common co-morbidities recorded. Pathogen co-detection occurred in
      24.7% of cases, most commonly with respiratory syncytial virus or a
      staphylococcal species. Median length of all ICU admissions was 3.2 days (range
      2.0 hours- 107.4 days) and 361 (51.3%) admissions required invasive respiratory
      support for a median duration of 4.3 days (range 0.2 hours- 107.5 days). There
      were 27 deaths recorded, 14 (51.9%) in children without a recorded co-morbidity.
      CONCLUSION: Influenza causes a substantial number of ICU admissions in Australian
      children each year with the majority occurring in previously healthy children.

PMID- 27023741
TI  - Mayo Clinic Zebrafish Facility Overview.
AB  - The zebrafish (Danio rerio) is a premier nonmammalian vertebrate model organism.
      This small aquatic fish is utilized in multiple disciplines in the Mayo Clinic
      community and by many laboratories around the world because of its biological
      similarity to humans, its advanced molecular genetics, the elucidation of its
      genome sequence, and the ever-expanding and outstanding new biological tools now
      available to the zebrafish researcher. The Mayo Clinic Zebrafish Facility (MCZF)
      houses ~2,000 tanks annotated using an in-house, Internet cloud-based bar-coding
      system tied to our established zfishbook.org web infrastructure. Paramecia are
      the primary food source for larval fish rearing, using a simplified culture
      protocol described herein. The MCZF supports the specific ongoing research in a
      variety of laboratories, while also serving as a local hub for new scientists as
      they learn to tap into the potential of this model system for understanding
      normal development, disease, and as models of health.

PMID- 27023742
TI  - Rapid, Long-Distance Electrical and Calcium Signaling in Plants.
AB  - Plants integrate activities throughout their bodies using long-range signaling
      systems in which stimuli sensed by just a few cells are translated into mobile
      signals that can influence the activities in distant tissues. Such signaling can
      travel at speeds well in excess of millimeters per second and can trigger
      responses as diverse as changes in transcription and translation levels,
      posttranslational regulation, alterations in metabolite levels, and even
      wholesale reprogramming of development. In addition to the use of mobile small
      molecules and hormones, electrical signals have long been known to propagate
      throughout the plant. This electrical signaling network has now been linked to
      waves of Ca(2+) and reactive oxygen species that traverse the plant and trigger
      systemic responses. Analysis of cell type specificity in signal propagation has
      revealed the movement of systemic signals through specific cell types, suggesting
      that a rapid signaling network may be hardwired into the architecture of the
      plant.

PMID- 27023744
TI  - Building a ladder to Hershey Heaven.
AB  - A genome-wide resource looks set to turn an experimental ideal into a reality for
      the Drosophila community.

PMID- 27023743
TI  - Non-enzymatic antioxidant capacity (NEAC) estimated by two different dietary
      assessment methods and its relationship with NEAC plasma levels.
AB  - PURPOSE: We aimed to quantify and compare dietary non-enzymatic antioxidant
      capacity (NEAC), estimated using two dietary assessment methods, and to explore
      its relationship with plasma NEAC. METHODS: Fifty healthy subjects volunteer to
      participate in this study. Two dietary assessment methods [a food frequency
      questionnaire (FFQ) and a 24-hour recall (24-HR)] were used to collect dietary
      information. Dietary NEAC, including oxygen radical absorbance capacity (ORAC),
      total polyphenols, ferric-reducing antioxidant power (FRAP) and trolox equivalent
      antioxidant capacity, was estimated using several data sources of NEAC content in
      food. NEAC status was measured in fasting blood samples using the same assays. We
      performed nonparametric Spearman's correlation analysis between pairs of dietary
      NEAC (FFQ and 24-HR) and diet-plasma NEAC, with and without the contribution of
      coffee's NEAC. Partial correlation analysis was used to estimate correlations
      regardless of variables potentially influencing these relationships. RESULTS: FFQ
      based NEAC and 24-HR-based NEAC were moderately correlated, with correlation
      coefficients ranging from 0.54 to 0.71, after controlling for energy intake, age
      and sex. Statistically significant positive correlations were found for dietary
      FRAP, either derived from the FFQ or the 24-HR, with plasma FRAP (r ~ 0.30). This
      weak, albeit statistically significant, correlation for FRAP was mostly present
      in the fruits and vegetables food groups. Plasma ORAC without proteins and 24-HR
      based total ORAC were also positively correlated (r = 0.35). CONCLUSION: The
      relationship between dietary NEAC and plasma FRAP and ORAC suggests the dietary
      NEAC may reflect antioxidant status despite its weak in vivo potential,
      supporting further its use in oxidative stress-related disease epidemiology.

PMID- 27023745
TI  - Electromechanical transducer for rapid detection, discrimination and
      quantification of lung cancer cells.
AB  - Tumor cells are malignant derivatives of normal cells. There are characteristic
      differences in the mechanophysical properties of normal and tumor cells, and
      these differences stem from the changes that occur in the cell cytoskeleton
      during cancer progression. There is a need for viable whole blood processing
      techniques for rapid and reliable tumor cell detection that do not require
      tagging. Micropore biosensors have previously been used to differentiate tumor
      cells from normal cells and we have used a micropore-based electromechanical
      transducer to differentiate one type of tumor cells from the other types. This
      device generated electrical signals that were characteristic of the cell
      properties. Three non-small cell lung cancer (NSCLC) cell lines, NCl-H1155, A549
      and NCI-H460, were successfully differentiated. NCI-H1155, due to their
      comparatively smaller size, were found to be the quickest in translocating
      through the micropore. Their translocation through a 15 MUm micropore caused
      electrical pulses with an average translocation time of 101 +/- 9.4 MUs and an
      average peak amplitude of 3.71 +/- 0.42 MUA, whereas translocation of A549 and
      NCI-H460 caused pulses with average translocation times of 126 +/- 17.9 MUs and
      148 +/- 13.7 MUs and average peak amplitudes of 4.58 +/- 0.61 MUA and 5.27 +/-
      0.66 MUA, respectively. This transformation of the differences in cell properties
      into differences in the electrical profiles (i.e. the differences in peak
      amplitudes and translocation times) with this electromechanical transducer is a
      quantitative way to differentiate these lung cancer cells. The solid-state
      micropore device processed whole biological samples without any pre-processing
      requirements and is thus ideal for point-of-care applications.

PMID- 27023746
TI  - Screw fixation for atlantoaxial dislocation related to Down syndrome in children
      younger than 5 years.
AB  - The aim of this study was to present cases of upper cervical fixation in Down
      syndrome patients younger than 5 years. In two cases, C1 lateral mass screws were
      installed. However, owing to the irreducible atlantoaxial dislocation, the screw
      backed out and fractured. Therefore, O-C2 fusion was performed. Furthermore, C2
      bilateral lamina screws were added to the C2 pedicle screw for reinforcement. C1
      C2 fusion is an option for Down syndrome patients younger than 5 years with
      atlantoaxial dislocation, when the dislocation is reducible. If the dislocation
      is irreducible, or the implant cannot be firmly secured, the fixation range
      should be expanded to O-C2 or below.

PMID- 27023747
TI  - Prognostic Significance of Dickkopf-1 in Gastric Cancer Survival: A Meta
      Analysis.
AB  - AIMS: The prognostic role of dickkopf-1 (DKK1) in gastric cancer (GC) remains
      poorly characterized. We performed a meta-analysis to evaluate correlations
      between DKK1 overexpression and the prognosis of patients with GC. MATERIALS AND
      METHODS: We included five published studies to assess the relationship between
      DKK1 and the clinicopathological characteristics and overall survival of GC
      patients. Literature searches, article selection, data collection, and
      statistical analysis were performed using RevMan 5.3 software. RESULTS: Our
      analyses revealed that DKK1 overexpression was significantly associated with
      vascular invasion (odds ratio [OR] = 2.43, 95% confidence interval [CI] = [1.21,
      4.89], p = 0.01, random effect), lymphatic invasion (OR = 2.61, 95% CI = [1.30,
      5.24], p = 0.007, random effect), and distant metastasis (OR = 2.99, 95% CI =
      [1.95, 4.59], p < 0.00001, fixed effect). Moreover, we also found that DKK1
      overexpression was significantly associated with poor overall survival in GC
      patients (risk ratio = 2.67, 95% CI = [2.24, 3.48], p < 0.00001, fixed effect).
      CONCLUSION: This meta-analysis demonstrated that DKK1 may be a useful prognostic
      marker for GC.

PMID- 27023748
TI  - Self-expanding stent for spontaneous coronary artery dissection: a rational
      choice.
AB  - : Spontaneous coronary artery dissection (SCAD) is a rare and poorly understood
      cause of acute coronary syndrome in relatively young patients. Nowadays, the
      optimal treatment of SCAD is uncertain. A conservative approach seems to be
      preferable, but in particular conditions, an invasive strategy is necessary. The
      poor rate of procedural success, the high risk of procedural complications and
      the uncertain long and mid-term results make the interventional treatment of SCAD
      a challenge. We report a case of a young male patient presenting with SCAD
      successfully treated with a sirolimus-eluting self-expanding coronary stent. To
      our knowledge, the use of self-expanding coronary stent for SCAD has never been
      described yet and we discuss about the rationale of a possible larger use in
      clinical practice.

PMID- 27023751
TI  - High-Performance p-Type Black Phosphorus Transistor with Scandium Contact.
AB  - A record high current density of 580 MUA/MUm is achieved for long-channel, few
      layer black phosphorus transistors with scandium contacts after 400 K vacuum
      annealing. The annealing effectively improves the on-state current and Ion/Ioff
      ratio by 1 order of magnitude and the subthreshold swing by ~2.5*, whereas Al2O3
      capping significantly degrades transistor performances, resulting in 5* lower on
      state current and 3* lower Ion/Ioff ratio. The influences of moisture on black
      phosphorus metal contacts are elucidated by analyzing the hysteresis of 3-20 nm
      thick black phosphorus transistors with scandium and gold contacts under
      different conditions: as-fabricated, after vacuum annealing, and after Al2O3
      capping. The optimal black phosphorus film thickness for transistors with
      scandium contacts is found to be ~10 nm. Moreover, p-type performance is shown in
      all transistors with scandium contacts, suggesting that the Fermi level is pinned
      closer to the valence band regardless of the flake thickness.

PMID- 27023749
TI  - Prevalence of Insulin Pump Therapy and Its Association with Measures of Glycemic
      Control: Results from the Canadian Study of Longevity in Type 1 Diabetes.
AB  - OBJECTIVE: We aimed to determine cross-sectional insulin pump prevalence and
      factors associated with measures of glycemic control as a secondary analysis in a
      long-standing type 1 diabetes mellitus (T1DM) national cohort. RESEARCH DESIGN
      AND METHODS: Canadian participants with >=50 years of T1DM (n = 305) were
      administered a comprehensive mail-based questionnaire including acquisition of
      contemporaneous laboratory results. Factors associated with pump use,
      glycosylated hemoglobin (HbA1c), and hypoglycemia were analyzed by regression.
      RESULTS: The 305 participants had a median age of 65 [interquartile range, 59,
      71] years, median diabetes duration of 54 [51, 59] years, and mean HbA1c level of
      7.5 +/- 1.1%. Prevalence of pump use was 44% (133/305), with median duration of
      use 8 [4, 13] years. Compared with the non-pump subgroup, the pump subgroup had
      numerically lower but similar HbA1c levels (7.4 +/- 0.9% vs. 7.6 +/- 1.2%; P =
      0.22) and reported greater numbers of minor hypoglycemia events (6.5 vs. 5.1
      events/patient.month; P = 0.004) and fewer severe hypoglycemia events (0.5 vs.
      1.3 events/patient.year; P = 0.02) in the past year. More frequent daily glucose
      tests and more frequent minor hypoglycemia events-but not pump therapy or its
      prescription parameters-were independently associated with lower HbA1c level in
      multivariable regression. However, use of insulin pump and habitual use of
      continuous glucose monitoring (>=1 week/month) were each independently associated
      with lower risk of severe hypoglycemia (risk ratio = 0.50 [P < 0.0001] and 0.30
      [P = 0.001], respectively). CONCLUSIONS: Insulin pump and continuous glucose
      monitoring technologies were associated with lower risk of severe hypoglycemia,
      while frequent daily glucose testing was associated with lower HbA1c level. These
      findings imply that basic self-management skill and technology play complementary
      roles in glycemic control among older adults with long-standing T1DM.

PMID- 27023750
TI  - TLR Agonist Augments Prophylactic Potential of Acid Inducible Antigen Rv3203
      against Mycobacterium tuberculosis H37Rv in Experimental Animals.
AB  - In general, the members of Lip gene family of Mycobacterium tuberculosis evoke
      strong immune response in the host. Keeping this fact into consideration, we
      investigated role of Rv3203, a cell wall associated protein with lipolytic
      activity, in imparting protection against experimental murine tuberculosis. The
      data of the present study suggested that archaeosome encapsulated Rv3203 induce
      strong lymphocyte proliferation, up-regulated Th-1 biased cytokines profile,
      increased expression of co-stimulatory markers on both antigen presenting cells
      and T lymphocytes. The immuno-prophylactic response was further modulated by
      exposure of the animals to zymosan, a TLR2/6 agonist, prior to immunization with
      archaeosome encapsulated Rv3203. Interestingly, pre-treatment of experimental
      animals with zymosan boosted strong immunological memory as compared to
      archaeosome encapsulated Rv3203 as well as BCG vaccine. We conclude that priming
      of immunized animal with TLR agonist followed by immunization with archaeosomes
      encapsulated Rv3203 offer substantial protection against tuberculosis infection
      and could be a potential subunit vaccine based prophylactic strategy. 

PMID- 27023753
TI  - Correction: The Spread of Dengue in an Endemic Urban Milieu-The Case of Delhi,
      India.

PMID- 27023752
TI  - Peering at Brain Polysomes with Atomic Force Microscopy.
AB  - The translational machinery, i.e., the polysome or polyribosome, is one of the
      biggest and most complex cytoplasmic machineries in cells. Polysomes, formed by
      ribosomes, mRNAs, several proteins and non-coding RNAs, represent integrated
      platforms where translational controls take place. However, while the ribosome
      has been widely studied, the organization of polysomes is still lacking
      comprehensive understanding. Thus much effort is required in order to elucidate
      polysome organization and any novel mechanism of translational control that may
      be embedded. Atomic force microscopy (AFM) is a type of scanning probe microscopy
      that allows the acquisition of 3D images at nanoscale resolution. Compared to
      electron microscopy (EM) techniques, one of the main advantages of AFM is that it
      can acquire thousands of images both in air and in solution, enabling the sample
      to be maintained under near physiological conditions without any need for
      staining and fixing procedures. Here, a detailed protocol for the accurate
      purification of polysomes from mouse brain and their deposition on mica
      substrates is described. This protocol enables polysome imaging in air and liquid
      with AFM and their reconstruction as three-dimensional objects. Complementary to
      cryo-electron microscopy (cryo-EM), the proposed method can be conveniently used
      for systematically analyzing polysomes and studying their organization. 

PMID- 27023754
TI  - First-principles investigation of ferroelectricity in LaBGeO5.
AB  - Density functional theory calculations are performed to characterize the
      structural, electronic and vibrational properties of both the low-temperature
      ferroelectric and high-temperature paraelectric phases of LaBGeO5. Phonon
      dispersion calculations for the high-temperature phase reveal an unstable mode
      whose zone-center eigenvector corresponds to a rigid rotation of the BO4
      tetrahedra, in agreement with previous calculations based on a short-range model
      potential. A possible switching path between two symmetry-equivalent
      ferroelectric phases that goes through the high-temperature paraelectric phase is
      identified and used to calculate the spontaneous polarization. The theoretical
      value for the spontaneous polarization calculated using the modern theory of
      polarization is 4.9 MUC cm(-2) for the PBEsol  +  U functional, which lies within
      the experimental range.

PMID- 27023755
TI  - HBsAg seroclearance or seroconversion induced by peg-interferon alpha and
      lamivudine or adefovir combination therapy in chronic hepatitis B treatment: a
      meta-analysis and systematic review.
AB  - BACKGROUND AND AIMS: Seroclearance or seroconversion of hepatitis B surface
      antigen (HBsAg) is generally considered as the clinical endpoint. The purpose of
      the present meta-analysis was to evaluate pegylated interferon alpha (PEG
      IFNalpha) with or without lamivudine (LAM) or adefovir (ADV) combination
      treatment in HBsAg seroclearance or seroconversion with CHB. METHODS: Randomized
      controlled trials of adults with CHB prior to May 30th 2015, with 48-52 weeks of
      PEG-IFNalpha and LAM or ADV combination therapy or monotherapy, were included.
      Review Manager Software 5.2.0 was used for meta-analysis. RESULTS: No statistical
      difference was noticed in HBsAg seroclearance (9.9% vs 7.1%, OR = 1.47, 95% CI
      0.75, 2.90; p = 0.26) or observed in HBsAg seroconversion (4.2% vs 3.7%, OR =
      1.17, 95% CI 0.57, 2.37; p = 0.67) between PEG-IFNalpha + LAM and PEG-IFNalpha +
      placebo for 24-26 weeks follow-up after treatment on hepatitis B e antigen
      (HBeAg)-positive CHB. Statistical difference was not showed in HBsAg
      disappearance (10.5% vs 6.4%, OR = 1.68, 95% CI 0.75, 3.76; p = 0.21) but was
      demonstrated in HBsAg seroconversion (6.3% vs 0%, OR = 7.22, 95% CI 1.23, 42.40;
      p = 0.03) between PEG-IFNalpha + ADV and PEG-IFNalpha for 48-52 weeks treatment
      on HBeAg-positive CHB By systematical evaluation, there were no differences in
      HBsAg disappearance and seroconversion between PEG-IFNalpha + placebo and PEG
      IFNalpha + LAM for 48-52 weeks treatment on HBeAg-positive CHB. There were no
      differences in HBsAg disappearance and seroconversion between PEG-IFNalpha +
      placebo and PEG-IFNalpha + LAM during 24 weeks to 3 years follow-up after
      treatment on HBeAg-negative CHB by systematical evaluation. CONCLUSION: The
      combination between PEG-IFNalpha and LAM or ADV was not superior to monotherapy
      of PEG-IFNalpha in terms of HBsAg seroclearance or seroconversion.

PMID- 27023756
TI  - Comparison of the Schwartz and CKD-EPI Equations for Estimating Glomerular
      Filtration Rate in Children, Adolescents, and Adults: A Retrospective Cross
      Sectional Study.
AB  - BACKGROUND: Estimating kidney glomerular filtration rate (GFR) is of utmost
      importance in many clinical conditions. However, very few studies have evaluated
      the performance of GFR estimating equations over all ages and degrees of kidney
      impairment. We evaluated the reliability of two major equations for GFR
      estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin
      as gold standard. METHODS AND FINDINGS: The study included 10,610 participants
      referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot
      Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first
      measurement kept for analysis) then estimated with isotope dilution mass
      spectrometry (IDMS)-traceable CKD-EPI and Schwartz equations. The participants'
      ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m2. A
      linear mixed-effects model was used to model the bias (mean ratio of estimated
      GFR to measured GFR). Equation reliability was also assessed using precision
      (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated
      GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR).
      In the whole sample, the mean ratio with the CKD-EPI equation was significantly
      higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08
      [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60-89 ml/min/1.73 m2,
      the mean ratios with the Schwartz equation were closer to 1 than the mean ratios
      with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus
      1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18-40 y), the
      Schwartz equation had a better precision and was also more accurate than the CKD
      EPI equation at GFR values under 60 ml/min/1.73 m2 (IQR: 0.32 [95% CI 0.28; 0.33]
      versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95%
      CI 59.7; 68.0]) and also at GFR values of 60-89 ml/min/1.73 m2. In all patients
      aged >=65 y, the CKD-EPI equation performed better than the Schwartz equation
      (IQR: 0.33 [95% CI 0.31; 0.34] versus 0.40 [95% CI 0.38; 0.41]; P30: 77.6 [95% CI
      75.7; 79.5] versus 67.5 [95% CI 65.4; 69.7], respectively). In children and
      adolescents (2-17 y), the Schwartz equation was superior to the CKD-EPI equation
      (IQR: 0.23 [95% CI 0.21; 0.24] versus 0.33 [95% CI 0.31; 0.34]; P30: 88.6 [95% CI
      86.7; 90.4] versus 29.4 [95% CI 26.8; 32.0]). This study is limited by its
      retrospective design, single-center setting with few non-white patients, and
      small number of patients with severe chronic kidney disease. CONCLUSIONS: The
      results from this study suggest that the Schwartz equation may be more reliable
      than the CKD-EPI equation for estimating GFR in children and adolescents and in
      adults with mild to moderate kidney impairment up to age 40 y.

PMID- 27023757
TI  - Valence Electronic Structure of Aqueous Solutions: Insights from Photoelectron
      Spectroscopy.
AB  - The valence orbital electron binding energies of water and of embedded solutes
      are crucial quantities for understanding chemical reactions taking place in
      aqueous solution, including oxidation/reduction, transition-metal coordination,
      and radiation chemistry. Their experimental determination based on liquid
      photoelectron spectroscopy using soft X-rays is described, and we provide an
      overview of valence photoelectron spectroscopy studies reported to date. We
      discuss principal experimental aspects and several theoretical approaches to
      compute the measured binding energies of the least tightly bound molecular
      orbitals. Solutes studied are presented chronologically, from simple
      electrolytes, via transition-metal ion solutions and several organic and
      inorganic molecules, to biologically relevant molecules, including aqueous
      nucleotides and their components. In addition to the lowest vertical ionization
      energies, the measured valence photoelectron spectra also provide information on
      adiabatic ionization energies and reorganization energies for the oxidation
      (ionization) half-reaction. For solutes with low solubility, resonantly enhanced
      ionization provides a promising alternative pathway.

PMID- 27023758
TI  - Computational Amide I 2D IR Spectroscopy as a Probe of Protein Structure and
      Dynamics.
AB  - Two-dimensional infrared spectroscopy of amide I vibrations is increasingly being
      used to study the structure and dynamics of proteins and peptides. Amide I, a
      primarily carbonyl stretching vibration of the protein backbone, provides
      information on secondary structures as a result of vibrational couplings and on
      hydrogen-bonding contacts when isotope labeling is used to isolate specific
      sites. In parallel with experiments, computational models of amide I spectra that
      use atomistic structures from molecular dynamics simulations have evolved to
      calculate experimental spectra. Mixed quantum-classical models use spectroscopic
      maps to translate the structural information into a quantum-mechanical
      Hamiltonian for the spectroscopically observed vibrations. This allows one to
      model the spectroscopy of large proteins, disordered states, and protein
      conformational dynamics. With improvements in amide I models, quantitative
      modeling of time-dependent structural ensembles and of direct feedback between
      experiments and simulations is possible. We review the advances in developing
      these models, their theoretical basis, and current and future applications.

PMID- 27023759
TI  - The Independence of the Junior Scientist's Mind: At What Price?
AB  - When I was facing the daunting task of recounting my approximately 70 years of
      scientific career and some aspects of my personal life, I decided to write this
      autobiographical piece in a "different" way. After a section on the almost bare
      facts of my life (Section 1), I include several other parts, loosely connected in
      time, in each of which I make an almost self-contained point, decreasing in this
      way the need for consistency and coherence in the whole article. I discuss, for
      example, the importance of original ideas, the independence of junior colleagues,
      and my work with molecular beams and in nanomedicine. I end by acknowledging
      those I was lucky enough to learn from in my intellectual development as a
      research scientist and with a couple of recommendations that may be useful to my
      junior and not-so-junior colleagues.

PMID- 27023760
TI  - Lack of Serum Creatinine Decrease After Coronary Angiography Despite Prophylactic
      Hydration After Routine Coronary Angiography/Angioplasty in Stable Angina
      Patients--Pilot Study.
AB  - BACKGROUND/AIMS: To prevent contrast induced renal dysfunction a periprocedural
      prophylactic hydration is applied. Due to dilution it should cause a drop in
      serum creatinine concentration (SCR). Surprisingly, no reduction in SCR after
      contrast admission is found in up to 25% of patients as early as 12-18 hours
      after coronary angiography/angioplasty. This study aims to find a clinical
      explanation as well as predict circumstances for this phenomenon. METHODS:
      Retrospective clinical and laboratory data was used from 341 patients who
      underwent elective coronary angiography/angioplasty, received a prophylactic
      hydration, and had serum creatinine concentration measured prior to, and 12-18
      hours after invasive procedure with iodine contrast administration. To exclude an
      improper hydration due to no creatinine decrease, the number of red blood cells
      was analysed as well as hemoglobin and hematocrit in blood donations collected
      during the study time points. RESULTS: The resulting lack of serum creatinine
      reduction could be explained by dehydration (measured by increase in number of
      RBC, HGB and HCT) only in 13.5% , 10.8%, and 20% of cases, respectively. Any form
      of abnormal glucose metabolism combined with either baseline serum creatinine
      concentration <0.87 mg/dL or creatinine clearance >86.77 mL/min, or GFR by CKD
      EPI >80.08 mL/min/1.73 m2, or GFR by MDRD >74.48 mL/min/1.73 m2 were the
      predictors for no creatinine decrease at outcome. Additionally, it was
      demonstrated that the lack of creatinine decrease was more often observed among
      those patients whose initial renal function was better than in the subjects with
      reduction of SCR. CONCLUSIONS: This observation requires further prospective
      investigation on extended group of patients.

PMID- 27023761
TI  - Expert Guide to Rheumatology Yee Arthur MF Paget Stephen A Expert Guide to
      Rheumatology 494 American College of Physicians 9781930513556 1930513550.
AB  - This American text is designed for clinicians, primarily rheumatologists, but
      will also be useful for nurse specialist and nurse practitioners who are
      increasingly developing their clinical roles and running their own clinics.

PMID- 27023762
TI  - What Can One Person do? Faith to Heal a Broken World Alkire Sabina Newell Edmund
      What Can One Person do? Faith to Heal a Broken World 200 Darton, Longman and Todd
      9780232526554 0232526559.
AB  - At the time of the funeral of Pope John Paul II, the religious commentator
      Clifford Longley said in an interview: 'Religion has never been more exciting.'
      Following the tragic events of the London bombings in the summer of the same
      year, many people may well have felt that religion was out of control.

PMID- 27023763
TI  - How to Have a Good Death: Preparing and Planning, With Informed Choices and
      Practical Advice Rantzen Esther How to Have a Good Death: Preparing and Planning,
      With Informed Choices and Practical Advice 192 Dorling Kindersley 9781405316293
      1405316292.
AB  - Linked to the BBC 2 programme shown at the end of March, this book attempts to
      help readers through the terror of death. Hospice philosophy encourages those who
      work with the dying to see themselves as 'midwives' at the end of life.

PMID- 27023764
TI  - Evaluation of PolyMPC-Dox Prodrugs in a Human Ovarian Tumor Model.
AB  - A polymer prodrug, composed of doxorubicin (Dox) conjugated covalently to
      poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), was evaluated for the
      treatment of human ovarian tumors in animals. PolyMPC-Dox prodrugs were prepared
      using facile conjugation chemistry to yield conjugates soluble in water and
      injectable saline, with a Dox loading of ~19 weight percent. Toxicity evaluation
      showed that polyMPC was well-tolerated in mice at doses up to 800 mg/kg,
      confirming the biocompatibility of the polymer carrier at a high concentration.
      Additionally, the polyMPC-Dox prodrug was well-tolerated in animals at a Dox
      equivalent dose of 10 mg/kg, greater than twice the maximum tolerated dose of
      free Dox (~4 mg/kg) in the same mouse strain. In a human ovarian tumor model
      (SKOV-3), polyMPC-Dox accumulated in tumors at twice the level of free Dox, with
      no additional off-target organ uptake, a result of improved pharmacokinetics
      afforded by the prodrug and passive targeting attributed to an enhanced
      permeability and retention effect. When administered to human ovarian tumor
      bearing mice using a recurring dosing regimen comparable to that used clinically,
      polyMPC-Dox significantly retarded tumor growth relative to treatment with free
      Dox. Moreover, animals treated with multiple doses of polyMPC-Dox (eight total
      doses) exhibited enhanced survival, with a notably reduced incidence of toxicity
      or adverse events relative to mice treated with free Dox. These in vivo results
      demonstrate advantages of treating human ovarian tumors with polyMPC-Dox,
      including reduced systemic toxicity, improved drug accumulation in tumors, and
      enhanced therapeutic efficacy.

PMID- 27023765
TI  - The Effect of Extracellular Calcium on Oxytocin-Induced Contractility in Naive
      and Oxytocin-Pretreated Human Myometrium In Vitro.
AB  - BACKGROUND: Prolonged exposure to oxytocin during augmentation of labor is a
      significant risk factor for uterine atony, resulting in the desensitization
      phenomenon, a decrease in the responsiveness of myometrium to further oxytocin.
      The importance of extracellular calcium is well established in spontaneous
      myometrial contractility; however, its significance is unknown in the context of
      desensitized myometrium. We aimed to investigate the effect of low, normal, and
      high extracellular calcium concentration on oxytocin-induced contractility in
      oxytocin-pretreated human myometrium in vitro. We hypothesized that extracellular
      normocalcemia would provide superior oxytocin-induced contractility in both naive
      and oxytocin-pretreated myometrium compared with hypocalcemia and hypercalcemia.
      METHODS: Myometrial tissue was obtained from women undergoing elective cesarean
      deliveries and was dissected into longitudinal strips. Each strip was mounted in
      a single organ bath with physiological salt solution (PSS) under homeostatic
      conditions and then pretreated for 2 hours with either oxytocin 10 M or PSS
      (control). The tissue was then washed with PSS, and calcium concentrations were
      altered to reflect low (1.25 mM), normal (2.5 mM), or high (3.75 mM) levels,
      thereby providing 6 study groups. After equilibration in the desired calcium
      concentration, a dose-response testing to oxytocin 10 M to 10 M was performed.
      Contractile parameters were measured and compared among groups after square root
      transformation. The primary outcome was motility index (frequency * amplitude),
      and secondary outcomes included frequency, amplitude, and area under the curve.
      RESULTS: One hundred seventy-four experiments were conducted from samples
      obtained from 36 women. In the control group, the mean motility index
      (?g.contractions/10 min) was significantly lower in the hypocalcemic group than
      in the normocalcemic group (estimated difference, -0.43; 95% confidence interval
      [CI], -0.82 to -0.04; P = 0.03). In addition, the mean frequency of contractions
      (?contractions/10 min) was significantly lower in the hypocalcemic (estimated
      difference, -0.27; 95% CI, -0.46 to -0.09; P = 0.002) and hypercalcemic groups
      (estimated difference, -0.18; 95% CI, -0.34 to -0.02; P = 0.03) compared with the
      normocalcemic group. In the oxytocin-pretreated group, there were no significant
      differences in the values of any of the contractility parameters of the
      hypocalcemic or hypercalcemic groups compared with the normocalcemic group (mean
      motility index [?g.contractions/10 min] estimated difference, 0.10; 95% CI, -0.23
      to 0.43; P = 0.74 and -0.39; 95% CI, -1.10 to 0.32; P = 0.39, respectively).
      CONCLUSIONS: In oxytocin-naive myometrium, normocalcemia provides superior
      oxytocin-induced contractility compared with hypocalcemic and hypercalcemic
      conditions. We were unable to draw conclusions regarding oxytocin-pretreated
      myometrium because of the small sample size relative to the large variability of
      the data. These observations warrant further investigations in laboratory and
      clinical settings.

PMID- 27023767
TI  - Understanding the Kinetics and Spectroscopy of Photoredox Catalysis and
      Transition-Metal-Free Alternatives.
AB  - Over the past decade, the field of photoredox catalysis has gained increasing
      attention in synthetic organic chemistry because of its wide applicability in
      sustainable free-radical-mediated processes. Numerous examples have shown that
      under carefully optimized conditions, efficient and highly selective processes
      can be developed through excitation of a photosensitizer using inexpensive,
      readily available light sources. However, despite all of these recent
      advancements, some generalizations and/or misconceptions have become part of the
      photoredox culture, and often many of these discoveries lack in-depth
      investigations into the excited-state kinetics and underlying mechanisms. In this
      Account, we begin with a tutorial for understanding both the redox properties of
      excited states and how to measure the kinetics of excited-state processes. We
      discuss the generalization of direct excitation of closed-shell species to
      generate more potent reductive or oxidative excited states, using the helium atom
      as a quantitative example. We also outline how to apply redox potentials to
      calculate whether the proposed electron transfer events are thermodynamically
      feasible. In the second half of our tutorial, we discuss how to measure the
      kinetics of excited-state processes using techniques such as steady-state and
      time-resolved fluorescence and transient spectroscopy and how to apply the data
      using Stern-Volmer and kinetic analysis. Then we shift gears to discuss our
      recent contributions to the field of photoredox catalysis. Our lab focuses on
      developing transition-metal-free alternatives to ruthenium and iridium bipyridyl
      complexes for these transformations, with the goal of developing systems in which
      the reaction kinetics is more favorable. We have found that methylene blue, a
      member of the thiazine dye family, can be employed in photoredox processes such
      as oxidative hydroxylations of arylboronic acids to phenols. Interestingly, we
      were able to demonstrate that methylene blue is more efficient for this reaction
      than Ru(bpy)3Cl2, which upon further examination using transient spectroscopic
      techniques we were able to relate to the reductive quenching ability of the
      aliphatic amine. Recently we were also successful in applying methylene blue for
      radical trifluoromethylation reactions, which is discussed in detail. Finally, we
      have also demonstrated that common organic electron donors, such as alpha
      sexithiophene, can be used in photoredox processes, which we demonstrate using
      the dehalogenation of vic-dibromides as a model system. This is a particularly
      interesting system because well-defined, long-lived intermediates allowed us to
      fully characterize the catalytic cycle. Once again, through an in-depth kinetic
      analysis we were able to gain valuable insights into our reaction mechanism,
      which demonstrates how powerful a tool proper kinetic analysis can be in the
      design and optimization of photoredox processes.

PMID- 27023766
TI  - Inhaled Anesthetics Exert Different Protective Properties in a Mouse Model of
      Ventilator-Induced Lung Injury.
AB  - BACKGROUND: Mechanical ventilation is an important perioperative tool in
      anesthesia and a lifesaving treatment for respiratory failure, but it can lead to
      ventilator-associated lung injury. Inhaled anesthetics have demonstrated
      protective properties in various models of organ damage. We compared the lung
      protective potential of inhaled sevoflurane, isoflurane, and desflurane in a
      mouse model of ventilator-induced lung injury (VILI). METHODS: C57BL/6N mice were
      randomized into 5 groups (n = 8/group). One group served as a control and 4
      groups were subjected to mechanical ventilation with air (12 mL/kg tidal volume)
      for 6 hours. Ventilated animals were anesthetized with either ketamine and
      acepromazine, or 1 of 3 inhaled anesthetics: isoflurane, sevoflurane, or
      desflurane. Lung injury was assessed by lung histology, neutrophil counts, and
      interleukin-1beta concentrations in bronchoalveolar lavage fluid. Antioxidant
      effects were explored by evaluation of production of reactive oxygen species
      (ROS) and glutathione content in lung tissue by immunofluorescence staining and
      confocal laser scanning microscopy. Changes in intercellular adhesion molecule-1
      and src-protein-tyrosine-kinase levels were determined by real-time polymerase
      chain reaction and Western blot. RESULTS: Compared with nonventilated controls,
      ventilated mice anesthetized with ketamine had thickened alveolar walls, elevated
      VILI scores, higher polymorph neutrophil counts, and increased ROS production.
      Mice anesthetized with isoflurane and sevoflurane showed thinner alveolar septa,
      lower VILI scores, lower polymorph neutrophil counts, and lower interleukin-1beta
      concentrations than ketamine mice. The expression of intercellular adhesion
      molecule-1/src-protein-tyrosine-kinase was neither affected by mechanical
      ventilation nor affected by administration of inhaled anesthetics. Mice
      anesthetized with isoflurane and sevoflurane showed less ROS production and
      higher glutathione contents compared with ketamine mice. Unexpectedly, desflurane
      ventilated mice showed similar signs of lung injury compared with mice ventilated
      with air alone and receiving ketamine anesthesia. Desflurane failed to inhibit
      inflammatory responses and ROS production in lung tissue and developed no
      antioxidant potential. CONCLUSIONS: Although isoflurane and sevoflurane prevent
      ventilator-associated lung injury, desflurane does not. As an underlying
      mechanism, both inhaled anesthetics exert major anti-inflammatory and
      antioxidative effects.

PMID- 27023769
TI  - Crystallographic and Spectroscopic Studies of a Host-Guest Complex Consisting of
      a Novel Zinc Trisporphyrinate and a Chiral Monoamine.
AB  - We have designed and synthesized a novel zinc trisporphyrinate with a benzene
      tricarboxamide as the linker. In the presence of a large excess of 1
      phenylethylamine, single crystals of the corresponding 1:3 host-guest complex
      were obtained, which provide the crystallographic structure of a host-guest
      complex consisting of an achiral porphyrin and a chiral monoamine. The structure
      reveals the 1-phenylethylamines adopt the "inside" binding mode that is
      stabilized by intramolecular hydrogen bonds. The NH2 of the 1-phenylethylamine is
      involved in both coordination and hydrogen bonding interactions. Circular
      dichroism (CD) and ultraviolet-visible spectra revealed that the 1:3 host-guest
      complex is dominant in the presence of a large excess of 1-phenylethylamine. The
      crystal structure shows there are two diastereomers of the 1:3 host-guest
      complexes. Density functional theory and TDDFT calculations suggest that one of
      the diastereomers is more energetically favorable, which dominates the CD
      signals. 

PMID- 27023768
TI  - Kinetic Characterisation of a Single Chain Antibody against the Hormone Abscisic
      Acid: Comparison with Its Parental Monoclonal.
AB  - A single-chain Fv fragment antibody (scFv) specific for the plant hormone
      abscisic acid (ABA) has been expressed in the bacterium Escherichia coli as a
      fusion protein. The kinetics of ABA binding have been measured using surface
      plasmon resonance spectrometry (BIAcore 2000) using surface and solution assays.
      Care was taken to calculate the concentration of active protein in each sample
      using initial rate measurements under conditions of partial mass transport
      limitation. The fusion product, parental monoclonal antibody and the free scFv
      all have low nanomolar affinity constants, but there is a lower dissociation rate
      constant for the parental monoclonal resulting in a three-fold greater affinity.
      Analogue specificity was tested and structure-activity binding preferences
      measured. The biologically-active (+)-ABA enantiomer is recognised with an
      affinity three orders of magnitude higher than the inactive (-)-ABA. Metabolites
      of ABA including phaseic acid, dihydrophaseic acid and deoxy-ABA have affinities
      over 100-fold lower than that for (+)-ABA. These properties of the scFv make it
      suitable as a sensor domain in bioreporters specific for the naturally occurring
      form of ABA. 

PMID- 27023771
TI  - FAIR principles for data stewardship.

PMID- 27023772
TI  - The gar is a fish... is a bird... is a mammal?
AB  - Teleosts have emerged as important model organisms, yet their ancestrally
      duplicated genomes sometimes complicate developmental genetic analyses and
      comparisons to humans. A new genome sequence of spotted gar, a fish related to
      teleosts but lacking a duplicated genome, now helps to bridge human and teleost
      biology. 

PMID- 27023770
TI  - Placenta-Enriched LincRNAs MIR503HG and LINC00629 Decrease Migration and Invasion
      Potential of JEG-3 Cell Line.
AB  - LINC00629 and MIR503HG are long intergenic non-coding RNAs (lincRNAs) mapped on
      chromosome X (Xq26), a region enriched for genes associated with human
      reproduction. Genes highly expressed in normal reproductive tissues and cancers
      (CT genes) are well known as potential tumor biomarkers. This study aimed to
      characterize the structure, expression, function and regulation mechanism of
      MIR503HG and LINC00629 lincRNAs. According to our data, MIR503HG expression was
      almost exclusive to placenta and LINC00629 was highly expressed in placenta and
      other reproductive tissues. Further analysis, using a cancer cell lines panel,
      showed that MIR503HG and LINC00629 were expressed in 50% and 100% of the cancer
      cell lines, respectively. MIR503HG was expressed predominantly in the nucleus of
      JEG-3 choriocarcinoma cells. We observed a positively correlated expression
      between MIR503HG and LINC00629, and between the lincRNAs and neighboring miRNAs.
      Also, both LINC00629 and MIR503GH could be negatively regulated by DNA
      methylation in an indirect way. Additionally, we identified new transcripts for
      MIR503HG and LINC00629 that are relatively conserved when compared to other
      primates. Furthermore, we found that overexpression of MIR503HG2 and the three
      exon LINC00629 new isoforms decreased invasion and migration potential of JEG-3
      tumor cell line. In conclusion, our results suggest that lincRNAs MIR503HG and
      LINC00629 impaired migration and invasion capacities in a choriocarcinoma in
      vitro model, indicating a potential role in human reproduction and tumorigenesis.
      Moreover, the MIR503HG expression pattern found here could indicate a putative
      new tumor biomarker. 

PMID- 27023773
TI  - Tet proteins enhance the developmental hourglass.
AB  - A new study compares DNA methylation profiles in developing zebrafish, Xenopus
      tropicalis and mice and suggests roles for Tet proteins in demethylating
      conserved gene enhancers during the phylotypic period of early development. These
      findings provide an epigenetic underpinning for the 'hourglass' model. 

PMID- 27023774
TI  - Recurrent mutation at the classical haptoglobin structural polymorphism.
AB  - Polymorphism of haptoglobin in human serum was first discovered over 60 years
      ago. A new paper characterizes the complex structural variation at the HP locus
      in detail and, by using imputation from flanking SNP genotype data, shows that it
      affects blood cholesterol levels. 

PMID- 27023775
TI  - Corrigendum: Mutations in the transcriptional repressor REST predispose to Wilms
      tumor.

PMID- 27023776
TI  - Corrigendum: Fine-mapping cellular QTLs with RASQUAL and ATAC-seq.

PMID- 27023777
TI  - Corrigendum: Germline RECQL mutations are associated with breast cancer
      susceptibility.

PMID- 27023778
TI  - Erratum: Multisystem Lewy body disease and the other parkinsonian disorders.

PMID- 27023779
TI  - Erratum: NRF2 regulates serine biosynthesis in non-small cell lung cancer.

PMID- 27023780
TI  - Meeting Abstracts - Annual Meeting 2016.
AB  - The AMCP Abstracts program provides a forum through which authors can share their
      insights and outcomes of advanced managed care practice through publication in
      AMCP's Journal of Managed Care & Specialty Pharmacy (JMCP). Most of the reviewed
      and unreviewed abstracts are presented as posters so that interested AMCP meeting
      attendees can review findings and query authors. The Student/Resident/ Fellow
      poster presentation (unreviewed) is Wednesday, April 20, 2016, and the
      Professional poster presentation (reviewed) is Thursday, April 21. The
      Professional posters will also be displayed on Friday, April 22. The reviewed
      abstracts are published in the JMCP Meeting Abstracts supplement. The AMCP
      Managed Care & Specialty Pharmacy Annual Meeting 2016 in San Francisco,
      California, is expected to attract more than 3,500 managed care pharmacists and
      other health care professionals who manage and evaluate drug therapies, develop
      and manage networks, and work with medical managers and information specialists
      to improve the care of all individuals enrolled in managed care programs.
      Abstracts were submitted in the following categories: Research Report: describe
      completed original research on managed care pharmacy services or health care
      interventions. Examples include (but are not limited to) observational studies
      using administrative claims, reports of the impact of unique benefit design
      strategies, and analyses of the effects of innovative administrative or clinical
      programs. Economic Model: describe models that predict the effect of various
      benefit design or clinical decisions on a population. For example, an economic
      model could be used to predict the budget impact of a new pharmaceutical product
      on a health care system. Solving Problems in Managed Care: describe the specific
      steps taken to introduce a needed change, develop and implement a new system or
      program, plan and organize an administrative function, or solve other types of
      problems in managed care settings. These abstracts describe a course of events;
      they do not test a hypothesis, but they may include data. 

PMID- 27023781
TI  - Role of intraluminal bowel echogenicity on prenatal ultrasounds to determine the
      anatomical level of intestinal atresia.
AB  - OBJECTIVE: To evaluate the correlation between different degrees of bowel
      intraluminal echogenicity showed by prenatal ultrasounds and the anatomic level
      of intestinal atresia. METHODS: We report three cases of intestinal atresia at
      different intestinal levels verified during the neonatal surgery with specific
      ultrasonographic prenatal features. Intensity of sonolucency was analyzed using
      the image-processing program ImageJ for quantitative measurements based on the
      gray-scale intensity values. RESULTS: A total of three cases are reported, a
      jejunal, an ileal and a colonic atresia. All cases showed intestinal dilatation.
      Both, jejunal and ileal atresia, showed two degrees of hypoechoic intestinal
      content, while colonic atresia showed hyperechogenic content dilated loop at
      prenatal ultrasound scan. CONCLUSIONS: We propose the use of prenatal ultrasounds
      echogenicity of intestinal dilated loop fluid content to help in determining the
      level of obstruction in bowel atresia. These are initial results, to be confirmed
      by a multicentric research with more cases.

PMID- 27023782
TI  - Pregnancy and lactation period: Which local anesthetics and analgesics?
AB  - The aim of this paper is to show relevant aspects of dental treatment in
      pregnancy. Common medication used in dental offices should be highlighted in
      special regard to the pregnant patient during dental treatment. The reader should
      gain more security in the election of the proper drugs for local anesthesia and
      oral analgesics. Local anaesthetics such as articain with adrenalin in a dilution
      of 1 : 200 000 can be used for dental treatment at any time. Paracetamol should
      be used as first line oral analgesic. Elective dental procedures should be
      postponed after delivery and after lactation period.

PMID- 27023783
TI  - Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis
      Patients.
AB  - OBJECTIVE: Hypomagnesemia has been associated with an increase in mortality among
      the general population as well as patients with chronic kidney disease or those
      on hemodialysis. However, this association has not been thoroughly studied in
      patients undergoing peritoneal dialysis. The aim of this study was to evaluate
      the association between serum magnesium concentrations and all-cause and
      cardiovascular mortalities in peritoneal dialysis patients. METHODS: This single
      center retrospective study included 253 incident peritoneal dialysis patients
      enrolled between July 1, 2005 and December 31, 2014 and followed to June 30,
      2015. Patient's demographic characteristics as well as clinical and laboratory
      measurements were collected. RESULTS: Of 253 patients evaluated, 36 patients
      (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months
      (range: 4-120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths
      were attributed to cardiovascular causes. Low serum magnesium was positively
      associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as
      serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160,
      p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and
      phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a
      lower survival rate than those in the normal magnesium groups (p < 0.001). In a
      multivariate Cox proportional hazards regression analysis, serum magnesium was an
      independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075,
      p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in
      female patients. However, in univariate and multivariate Cox analysis,
      ?Mg(difference between 1-year magnesium and baseline magnesium) was not an
      independent predictor of all-cause mortality and cardiovascular mortality.
      CONCLUSION: Hypomagnesemia was common among peritoneal dialysis patients and was
      independently associated with all-cause mortality and cardiovascular mortality.

PMID- 27023785
TI  - KRAKENX: software for the generation of alignment-independent 3D descriptors.
AB  - The KRAKENX software calculates a large variety of molecular descriptors based on
      quantum chemistry computations. The program supports over 2000 three-dimensional
      descriptors that are calculated from the output of different quantum chemistry
      packages. The current implementation supports semi-empirical MOPAC-based
      computations and primarily focuses on orientation-independent descriptors that
      have been discussed in the literature. The descriptor performance has been
      exemplified using a number of large and diverse datasets and can be seen to
      produce parsimonious linear models. The software can be run on multiple platforms
      and is available to academics free of charge. 

PMID- 27023784
TI  - mTOR Hyperactivation by Ablation of Tuberous Sclerosis Complex 2 in the Mouse
      Heart Induces Cardiac Dysfunction with the Increased Number of Small Mitochondria
      Mediated through the Down-Regulation of Autophagy.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell
      growth, proliferation and metabolism. mTORC1 regulates protein synthesis
      positively and autophagy negatively. Autophagy is a major system to manage bulk
      degradation and recycling of cytoplasmic components and organelles. Tuberous
      sclerosis complex (TSC) 1 and 2 form a heterodimeric complex and inactivate Ras
      homolog enriched in brain, resulting in inhibition of mTORC1. Here, we
      investigated the effects of hyperactivation of mTORC1 on cardiac function and
      structure using cardiac-specific TSC2-deficient (TSC2-/-) mice. TSC2-/- mice were
      born normally at the expected Mendelian ratio. However, the median life span of
      TSC2-/- mice was approximately 10 months and significantly shorter than that of
      control mice. TSC2-/- mice showed cardiac dysfunction and cardiomyocyte
      hypertrophy without considerable fibrosis, cell infiltration or apoptotic
      cardiomyocyte death. Ultrastructural analysis of TSC2-/- hearts revealed
      misalignment, aggregation and a decrease in the size and an increase in the
      number of mitochondria, but the mitochondrial function was maintained. Autophagic
      flux was inhibited, while the phosphorylation level of S6 or eukaryotic
      initiation factor 4E -binding protein 1, downstream of mTORC1, was increased. The
      upregulation of autophagic flux by trehalose treatment attenuated the cardiac
      phenotypes such as cardiac dysfunction and structural abnormalities of
      mitochondria in TSC2-/- hearts. The results suggest that autophagy via the TSC2
      mTORC1 signaling pathway plays an important role in maintenance of cardiac
      function and mitochondrial quantity and size in the heart and could be a
      therapeutic target to maintain mitochondrial homeostasis in failing hearts. 

PMID- 27023786
TI  - Relationship between Body Mass Index, C-Peptide, and Delta-5-Desaturase Enzyme
      Activity Estimates in Adult Males.
AB  - Obesity, in particular abdominal obesity, alters the composition of plasma and
      tissue fatty acids (FAs), which contributes to inflammation and insulin
      resistance. FA metabolism is modulated by desaturases and may affect adipokine
      and insulin secretion. Therefore, we examined relationships between adipokines, a
      marker of insulin production, and plasma FA desaturase enzyme activity estimates
      (EAEs) in obesity. Plasma phospholipid (PPL) FAs were isolated from 126 males
      (ages 48 to 65 years), derivatized, and analyzed using gas chromatography. Delta
      6 desaturase (D6D) and delta-5 desaturase (D5D) EAEs were calculated as the ratio
      of PPL 20:3/18:2 and 20:4/20:3, respectively. In body mass index (BMI) and waist
      circumference (WC) adjusted polytomous logistic regression analyses, PPL FAs and
      FA desaturase EAEs were associated with C-peptide and adiponectin. Individuals
      with elevated D6D EAEs were less likely (OR 0.33) to have serum adiponectin
      concentrations > 5.37 MUg/mL, compared with adiponectin concentrations <= 3.62
      MUg/mL. Individuals with increased D5D EAEs were less likely (OR 0.8) to have C
      peptide concentrations >= 3.32 ng/mL, and > 1.80 and <= 3.29 ng/mL, compared with
      those with C-peptide <= 1.76 ng/mL. The proinflammatory cytokine tumor necrosis
      factor-alpha (TNF-alpha) was positively associated with C-peptide, but TNF-alpha
      was not associated with the D5D EAE. C-peptide and adiponectin concentrations are
      associated with specific PPL FAs and FA desaturase EAEs. The relationship between
      C-peptide concentrations and D5D EAEs remained significant after adjusting for
      BMI, WC, and TNF-alpha. Thus, future research should investigate whether D5D
      inhibition may occur through a C-peptide mediated pathway.

PMID- 27023788
TI  - Optical Coherence Tomography Angiography of Retinal Artery Occlusion.
AB  - The optical coherence tomography angiography (OCTA) microvascular features of
      branch and central retinal artery occlusion are described and correlated with
      fluorescein angiographic and clinical findings. There may be differences in the
      distribution of reduced vascular perfusion/flow between the superficial and deep
      retinal capillary plexuses in retinal artery occlusive disease. The extent of
      macular ischemia and the status of flow in the radial peripapillary capillaries
      can be evaluated with OCTA. Overall, OCTA can be used to monitor changes in
      vascular flow during the clinical course of retinal artery occlusion. 

PMID- 27023787
TI  - Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas
      of Sabah, East Malaysia.
AB  - Malaysia has a national goal to eliminate malaria by 2020. Understanding the
      genetic diversity of malaria parasites in residual transmission foci can provide
      invaluable information which may inform the intervention strategies used to reach
      elimination targets. This study was conducted to determine the genetic diversity
      level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria
      active case detection was conducted in Kalabakan and Kota Marudu. All individuals
      in the study sites were screened for malaria infection by rapid diagnostic test.
      Blood from P. falciparum-infected individuals were collected on filter paper
      prior to DNA extraction. Genotyping was performed using merozoite surface protein
      1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP)
      and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of
      infection (MOI), mean number of alleles (Na), expected heterozygosity (He),
      linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In
      Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family
      types, respectively. The GLURP genotype VI (751-800 bp) was predominant. The MOI
      for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite
      locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites
      were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2
      alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP
      genotype IV (651-700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was
      1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2,
      GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A
      significant LD was observed in Kalabakan (0.495, p<0.01) and Kota Marudu P.
      falciparum populations (0.601, p<0.01). High genetic differentiation between
      Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0.532).
      The genetic data from the present study highlighted the limited diversity and
      contrasting genetic pattern of P. falciparum populations in the malaria declining
      areas of Sabah. 

PMID- 27023789
TI  - Brexpiprazole: A Review in Schizophrenia.
AB  - Oral brexpiprazole (Rexulti((r))) is a partial dopamine D2 agonist, which also
      has activity at several other receptors. This article reviews the pharmacological
      properties of brexpiprazole and its clinical efficacy and tolerability in
      patients with schizophrenia; its use in patients with major depressive disorder
      is beyond the scope of this review. Brexpiprazole 2-4 mg/day was generally
      effective in short-term, phase III studies at improving Positive and Negative
      Symptom Scale scores and other schizophrenia symptoms in patients with acute
      schizophrenia. Moreover, maintenance treatment with brexpiprazole 1-4 mg/day was
      associated with a significantly longer time to exacerbation of disease or
      impending relapse than placebo. The drug was well tolerated in clinical trials,
      with most serious adverse events in the short term being associated with the
      underlying disorder. Overall, oral brexpiprazole is a useful treatment option for
      the treatment of patients with schizophrenia. 

PMID- 27023790
TI  - Maintenance of a Drosophila melanogaster Population Cage.
AB  - Large quantities of DNA, RNA, proteins and other cellular components are often
      required for biochemistry and molecular biology experiments. The short life cycle
      of Drosophila enables collection of large quantities of material from embryos,
      larvae, pupae and adult flies, in a synchronized way, at a low economic cost. A
      major strategy for propagating large numbers of flies is the use of a fly
      population cage. This useful and common tool in the Drososphila community is an
      efficient way to regularly produce milligrams to tens of grams of embryos,
      depending on uniformity of developmental stage desired. While a population cage
      can be time consuming to set up, maintaining a cage over months takes much less
      time and enables rapid collection of biological material in a short period. This
      paper describes a detailed and flexible protocol for the maintenance of a
      Drosophila melanogaster population cage, starting with 1.5 g of harvested
      material from the previous cycle. 

PMID- 27023792
TI  - VOC-Induced Flexing of Single and Multilayer Polyethylene Films As Gas Sensors.
AB  - The differential swelling and bending of multilayer polymeric films due to the
      dissimilar uptake of volatile organic compounds (VOCs; n-hexane, limonene) in the
      different layers was studied. Motions of thin polyethylene films triggered by the
      penetrant were investigated to learn more about how their deformation is related
      to VOC absorption. Single layers of metallocene or low-density polyethylene, and
      multilayers (2-288 layers) of these in alternating positions were considered.
      Single-, 24-, and 288-layer films displayed no motion when uniformly subjected to
      VOCs, but they could display simple curving modes when only one side of the film
      was wetted with a liquid VOC. Two-layer films displayed simple bending when
      uniformly subjected to VOCs due to the different swelling in the two layers, but
      when the VOC was applied to only one side of the film, more complex modes of
      motion as well as dynamic oscillations were observed (e.g., constant amplitude
      wagging at 2 Hz for ca. 50 s until all the VOC had evaporated). Diffusion
      modeling was used to study the transport behavior of VOCs inside the films and
      the different bending modes. Finally a prototype VOC sensor was developed, where
      the reproducible curving of the two-layer film was calibrated with n-hexane. The
      sensor is simple, cost-efficient, and nondestructive and requires no electricity.

PMID- 27023793
TI  - High glucose intake and glycaemic level in critically ill neonates with inherited
      metabolic disorders of intoxication.
AB  - To investigate glycaemic levels in critically ill neonates with inherited
      metabolic disorders of intoxication. Thirty-nine neonates with a median age of 7
      days (0-24) were retrospectively included (urea cycle disorders (n = 18), maple
      syrup disease (n = 13), organic acidemias (n = 8)). Twenty-seven neonates were
      intubated, 21 were haemodialysed and 6 died. During the first 3 days, median
      total and peak blood glucose (BG) levels were 7.1 mmol/L (0.9-50) and 10 mmol/L
      (5.1-50), respectively. The median glucose intake rate was 11 mg/kg/min (2.7
      15.9). Fifteen and 23 neonates exhibited severe hyperglycaemia (>=2 BG levels >12
      mmol/L) and mild hyperglycaemia (>=2 BG levels >7 and <=12 mmol/L), respectively.
      Glycaemic levels and number of hyperglycaemic neonates decreased over the first 3
      days (p < 0.001) while total glucose intake rate was stable (p = 0.11). Enteral
      route of glucose intake was associated with a lower number of hyperglycaemic
      neonates (p = 0.04) and glycaemic level (p = 0.02). CONCLUSION: Hyperglycaemia is
      common in critically ill neonates receiving high glucose intake with inherited
      metabolic disorders of intoxication. Physicians should decrease the rate of total
      glucose intake and begin enteral feeding as quickly as possible in cases of
      persistent hyperglycaemia. WHAT IS KNOWN: * The risk of hyperglycaemia in the
      acute phase of critical illness is high. What is New: * Hyperglycaemia is common
      in the initial management of critically ill neonates with inherited metabolic
      disorders of intoxication receiving high glucose intake.

PMID- 27023791
TI  - Photosynthetic response to fluctuating environments and photoprotective
      strategies under abiotic stress.
AB  - Plants in natural environments must cope with diverse, highly dynamic, and
      unpredictable conditions. They have mechanisms to enhance the capture of light
      energy when light intensity is low, but they can also slow down photosynthetic
      electron transport to prevent the production of reactive oxygen species and
      consequent damage to the photosynthetic machinery under excess light. Plants need
      a highly responsive regulatory system to balance the photosynthetic light
      reactions with downstream metabolism. Various mechanisms of regulation of
      photosynthetic electron transport under stress have been proposed, however the
      data have been obtained mainly under environmentally stable and controlled
      conditions. Thus, our understanding of dynamic modulation of photosynthesis under
      dramatically fluctuating natural environments remains limited. In this review,
      first I describe the magnitude of environmental fluctuations under natural
      conditions. Next, I examine the effects of fluctuations in light intensity, CO2
      concentration, leaf temperature, and relative humidity on dynamic photosynthesis.
      Finally, I summarize photoprotective strategies that allow plants to maintain the
      photosynthesis under stressful fluctuating environments. The present work clearly
      showed that fluctuation in various environmental factors resulted in reductions
      in photosynthetic rate in a stepwise manner at every environmental fluctuation,
      leading to the conclusion that fluctuating environments would have a large impact
      on photosynthesis. 

PMID- 27023794
TI  - Influence of solid state fermentation by Trichoderma spp. on solubility, phenolic
      content, antioxidant, and antimicrobial activities of commercial turmeric.
AB  - The influence of solid state fermentation (SSF) by Trichoderma spp. on the
      solubility, total phenolic content, antioxidant, and antibacterial activities of
      turmeric was determined and compared with unfermented turmeric. The solubility of
      turmeric was monitored by increase in its phenolic content. The total phenolic
      content of turmeric extracted by 80% methanol and water after SSF by six species
      of Trichoderma spp. increased significantly from 2.5 to 11.3-23.3 and from 0.5 to
      13.5-20.4 GAE/g DW, respectively. The antioxidant activities of fermented
      turmeric were enhanced using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis
      (3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS), and ferric ion-reducing
      antioxidant power (FRAP) assays. The antibacterial activity of fermented turmeric
      against human-pathogenic bacteria Escherichia coli, Streptococcus agalactiae,
      Staphylococcus aureus, Entreococcus faecalis, Methicillin-Resistant S. aureus,
      Klebsiella pneumonia, and Pseudomonas aeruginosae showed a broad spectrum
      inhibitory effect. In conclusion, the results indicated the potentials of using
      fermented turmeric as natural antioxidant and antimicrobial material for food
      applications. 

PMID- 27023795
TI  - Long term morphological characterization of mesenchymal stromal cells 3D
      spheroids built with a rapid method based on entry-level equipment.
AB  - Three-dimensional (3D) spheroids of mesenchymal stromal cells (MSC) have been
      demonstrated to improve a wide range of MSC features, such as multilineage
      potential, secretion of therapeutic factors, and resistance against hypoxic
      condition. Accordingly, they represent a promising tool in regenerative medicine
      for several biological and clinical applications. Many approaches have been
      proposed to generate MSC spheroids. They usually require specific generation
      systems, such as rotatory bioreactors or low-attachment plates, and each approach
      has its own disadvantages. Furthermore, an over-time analysis of morphological
      homogeneity and architectural stability of the spheroids generated is rarely
      provided. In this work we adapted the "pellet culture" method to obtain
      homogenous spheroids of MSC and maintain them in vitro for long term studies. We
      analysed their outer and inner structure over a 2-month period to provide
      morphological and architectural information regarding the spheroids generated.
      Quantitative and qualitative data were obtained using brightfield and confocal
      microscope imaging coupled to a computational analysis to estimate volume,
      sphericity, and jagging degree. In addition, histological evaluation was
      performed to more thoroughly assess the cellular composition and the internal
      architecture of the 3D spheroids. The results provided show that MSC spheroids
      generated with the proposed approach are homogeneous and stable, from both
      morphological and architectural points of view, for a period of at least 15 days,
      approximately between day 15 and day 30 after their generation. Accordingly, the
      approach proposed serves as a rapid, cost-effective, and efficient method to
      generate and maintain MSC spheroids using common entry-level laboratory equipment
      only.

PMID- 27023796
TI  - Spontaneous coronary artery dissection treated with biovascular scaffolds guided
      by intravascular ultrasounds imaging.
AB  - We reported a case of a fit and active 48 years' old woman presented with acute
      coronary syndrome due to a spontaneous coronary dissection (SCAD) treated with
      bioresorbable scaffolds (BVS) implantation guided by intravascular ultrasounds
      (IVUS) with immediate and long-term good results.

PMID- 27023797
TI  - Tobacco, Microbes, and Carcinogens: Correlation Between Tobacco Cure Conditions,
      Tobacco-Specific Nitrosamine Content, and Cured Leaf Microbial Community.
AB  - Tobacco-specific nitrosamines are carcinogenic N-nitrosamine compounds present at
      very low levels in freshly harvested tobacco leaves that accumulate during leaf
      curing. Formation of N-nitrosamine compounds is associated with high nitrate
      levels in the leaf at harvest, and nitrate is presumed to be the source from
      which the N-nitrosation species originates. More specifically, nitrite is
      considered to be a direct precursor, and nitrite is linked with N-nitrosation in
      many environmental matrices where it occurs via microbial nitrate reduction.
      Here, we initiate work exploring the role of leaf microbial communities in
      formation of tobacco-specific nitrosamines. Leaves from burley tobacco line TN90H
      were air cured under various temperature and relative humidity levels, and 22
      cured tobacco samples were analyzed for their microbial communities and leaf
      chemistry. Analysis of nitrate, nitrite, and total tobacco-specific nitrosamine
      levels revealed a strong positive correlation between the three variables, as
      well as a strong positive correlation with increasing relative humidity during
      cure conditions. 16S rRNA gene amplicon sequencing was used to assess microbial
      communities in each of the samples. In most samples, Proteobacteria predominated
      at the phylum level, accounting for >90 % of the OTUs. However, a distinct shift
      was noted among members of the high tobacco-specific nitrosamine group, with
      increases in Firmicutes and Actinobacteria. Several OTUs were identified that
      correlate strongly (positive and negative) with tobacco-specific nitrosamine
      content. Copy number of bacterial nitrate reductase genes, obtained using
      quantitative PCR, did not correlate strongly with tobacco-specific nitrosamine
      content. Incomplete denitrification is potentially implicated in tobacco-specific
      nitrosamine levels.

PMID- 27023798
TI  - Optical Coherence Tomography Angiography of Type 2 Neovascularization in Age
      Related Macular Degeneration.
AB  - Well-defined choroidal neovascularization, known as type 2 neovascularization
      (NV) or classic NV, is the least representative phenotype of exudative age
      related macular degeneration. Clinical aspects of type 2 NV have been widely
      described in the literature, and to date fluorescein angiography remains the gold
      standard for imaging age-related macular degeneration at initial presentation.
      Optical coherence tomography angiography (OCT-A) can be used to image vessels
      based on flow characteristics without any dye injection. Type 2 NV can be
      visualized using OCT-A with very typical patterns. A neovascular membrane appears
      as either a medusa-shaped complex or a glomerulus-shaped lesion in the outer
      retina and the choriocapillaris layer. Furthermore, in the choriocapillaris
      layer, the external borders of the lesion appear as a dark ring in most cases,
      and one or more central feeder vessels that extend deeply into the more profound
      choroidal layers are visible. Identification of type 2 NV is easily feasible for
      any clinician using OCT-A, especially in areas where there are normally no
      vessels, like in subretinal space, if the interpretation rules are respected. 

PMID- 27023800
TI  - Fetal heart rate monitoring category 3 during the 2nd stage of labor is an
      independent predictor of fetal acidosis.
AB  - OBJECTIVE: To determine whether fetal heart rate (FHR) monitoring categories
      during the 1st and 2nd stage of labor can predict arterial cord pH <7.2.
      MATERIALS AND METHODS: A case control study was conducted including 653
      consecutive term deliveries (37 weeks gestation and above) that were divided
      according to fetal pH <= 7.2 (n = 315) and fetal pH > 7.2 (n = 338). Deliveries
      occurred during the year 2013 in tertiary medical center, where arterial cord pH
      is routinely taken after birth. Intrapartum FHR monitoring categorization was
      defined according to the ACOG committee guidelines by two obstetricians.
      Multivariable models were constructed to control for confounders. RESULTS:
      Variable decelerations, late decelerations and bradycardia during the 1st and 2nd
      stages of labor were significantly higher in group of deliveries ended in cord pH
      < 7.2 compared with group of deliveries ended in cord pH > 7.2. A significant
      association was observed between category 2 and 3 during the 1st stage of labor
      and pH <= 7.2. However, while controlling for FHR category 3 at the 2nd stage of
      labor, 1st stage categorization lost its association with pH <7.2, and only
      category 3 during the 2nd stage were noted as an independent risk factor for
      acidosis. CONCLUSION: FHR monitoring category 3 during the 2nd stage of labor is
      an independent predictor of fetal acidosis as expressed by arterial cord pH <
      7.2.

PMID- 27023799
TI  - Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide
      Levels on Inflammation and Metabolism in Human Differentiated Adipocytes.
AB  - Obesity is characterized by an excessive accumulation of fat in adipose tissue,
      which is associated with oxidative stress and chronic inflammation. Excessive
      H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in
      obesity. We investigated the effects of inhibition of catalase activity on
      metabolism and inflammation by incubating human differentiated adipocytes with 10
      mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased
      CAT activity and increased intracellular H2O2 levels significantly. Glutathione
      peroxidase (GPX) activity was also reduced, and the gene expression levels of the
      antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5) were inhibited.
      Interestingly, this occurred along with lower mRNA levels of the transcription
      factors nuclear factor (erythroid 2-like 2) and forkhead box O, which are
      involved in redox homeostasis. However, superoxide dismutase activity and
      expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) activation and increased tumor necrosis
      alpha and interleukin 6 protein and gene expression levels, while lowering
      peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA and protein
      levels. These alterations were accompanied by an altered glucose and lipid
      metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose
      uptake, reduced glucose transporter type 4 gene and protein expression, reduced
      lipolysis, reduced AMP-activated protein kinase activation and reduced gene
      expression of lipases. Our results indicate that increased H2O2 levels caused by
      3-AT treatment impair the antioxidant defense system, lower PPARgamma expression
      and initiate inflammation, thus affecting glucose and lipid metabolism in human
      differentiated adipocytes. 

PMID- 27023801
TI  - Structural Analysis of Perfluoropropanoyl Fluoride in the Gas, Liquid, and Solid
      Phases.
AB  - The coexistence of two conformers in perfluoropropanoyl fluoride, CF3CF2C(O)F,
      differing in the CC-CF dihedral angle (gauche 85(10)% and anti 15(10)%), has been
      determined by means of gas-phase electron diffraction (GED). Quantum-chemical
      calculations performed at the MP2 and B3LYP approximations and cc-pVTZ basis sets
      reproduce the experimental values with confidence. By contrast, FTIR spectra give
      no clear evidence for the anti-conformer in the gas phase. Information on this
      less abundant but stable rotamer is obtained from matrix-isolation/FTIR
      spectroscopy and liquid Raman spectroscopy. In situ crystallization and single
      crystal X-ray diffraction (XRD) data reveal the presence of solely the gauche
      conformation in the solid state. A set of intermolecular interactions including
      C?O...C?O, C-F...F-C, and F...C?O is detected. The nature of bonding and the
      relative stabilities of gauche- and anti-conformers are explored using natural
      bond orbitals. 

PMID- 27023802
TI  - Construction of the Syngonium podophyllum-Pseudomonas sp. XNN8 Symbiotic
      Purification System and Investigation of Its Capability of Remediating Uranium
      Wastewater.
AB  - The endophyte Pseudomonas sp. XNN8 was separated from Typha orientalis which can
      secrete indole-3-acetic acid and 1-aminocyclopropane-1-carboxylate deaminase and
      siderophores and has strong resistance to uranium it was then colonized in the
      Syngonium podophyllum; and the S. podophyllum-Pseudomonas sp. XNN8 symbiotic
      purification system (SPPSPS) for uranium-containing wastewater was constructed.
      Afterwards, the hydroponic experiments to remove uranium from uranium-containing
      wastewater by the SPPSPS were conducted. After 24 days of treatment, the uranium
      concentrations of the wastewater samples with uranium concentrations between 0.5
      and 5.0 mg/L were lowered to below 0.05 mg/L. Furthermore, the uranium in the
      plants was assayed using Fourier transform infrared spectroscopy (FTIR) and
      extended X-ray absorption fine structure (EXAFS) spectroscopy. The Pseudomonas
      sp. XNN8 was found to generate substantial organic groups in the roots of the
      Syngonium podophyllum, which could improve the complexing capability of S.
      podophyllum for uranium. The uranium in the roots of S. podophyllum was found to
      be the uranyl phosphate (47.4 %) and uranyl acetate (52.6 %).

PMID- 27023803
TI  - Investigation of fluorine content in PM2.5 airborne particles of Istanbul,
      Turkey.
AB  - Fluorine determination in airborne samples is important due to its spread into
      the air from both natural and artificial sources. It can travel by wind over
      large distances before depositing on the Earth's surface. Its concentration in
      various matrices are limited and controlled by the regulations for causing health
      risks associated with environmental exposures. In this work, fluorine was
      determined in PM2.5 airborne samples by high-resolution continuum source
      electrothermal atomic absorption spectrometry. For these purpose, the PM2.5
      airborne particulates were collected on quartz filters using high-volume samplers
      (500 L/min) in Istanbul (Turkey) for 96 h during January to June in 2 years.
      Then, instrumental and experimental parameters were optimized for the analyte in
      airborne samples. The validity of the method for the analyte was tested using
      standard reference material, and certified values were found in the limits of 95
      % confidence level. The fluorine concentrations and meteorological conditions
      were compared statistically. 

PMID- 27023804
TI  - Metal accumulation capacity of parasol mushroom (Macrolepiota procera) from
      Rasina region (Serbia).
AB  - During many years of industrial development, soil system was contaminated with
      large amounts of toxic metals. In order to investigate the mobility and
      availability of metals from soil to mushrooms, the content of 13 elements (Al,
      Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Ti, and Zn), in caps and stipes of wild
      grown edible mushroom Macrolepiota procera and soil substrates, collected from
      five sites in Rasina region in central Serbia, was determined. Soil samples were
      subjected to the sequential extraction procedure proposed by the Community Bureau
      of Reference in order to fractionate acid-soluble/exchangeable, reducible,
      oxidizable, and residual fractions. Metal concentrations were determined by
      inductively coupled plasma optical emission spectrometer and inductively coupled
      plasma mass spectrometer and the results subjected to multivariate data analysis.
      A principal component analysis distinguished mushrooms samples from different
      geographical areas and revealed the influence of soil composition on metal
      content in mushrooms. Hierarchical cluster analyses confirmed that the first
      three phases of extraction were the most important for metal uptake by mushrooms
      from soil. The bioconcentration factors and translocation factors for each metal
      were also calculated. These results showed that M. procera could serve as a good
      dietary source of essential elements, especially Cu, Zn, Mn, and Fe but the
      consumption of mushrooms may pose a health risk for consumers during the "season
      of mushrooms," due to the presence of cadmium. 

PMID- 27023805
TI  - Gaseous benzene degradation by photocatalysis using ZnO + Zn2TiO4 thin films
      obtained by sol-gel process.
AB  - The benzene pollutant in gaseous phase was successfully degraded by using ZnO +
      Zn2TiO4 multicomponent oxide thin films as photocatalysts. The films were
      obtained with different Ti/Zn ratios (0, 0.20, 0.40, 0.45, 0.50, 0.67, 0.84, and
      1) by the sol-gel route. The initial level of benzene concentration was 110 +/-
      10 ppm. The process was carried out under different conditions of relative
      humidity (RH): 25, 50, and 80 % in a batch-type reactor, at room temperature. The
      results show benzene degradation near to 95 % at t = 240 min, where the
      multicomponent oxide semiconductor has a Ti/Zn ratio of 0.67. Meanwhile, with the
      TiO2 thin films, only a degradation of 70 % was reached at the same measurement
      conditions. This synergistic effect on the photocatalytic activity is a result of
      the coupling of both semiconductor oxides. An adverse effect on the
      photocatalytic activity was observed as the relative humidity increases. 

PMID- 27023806
TI  - The occurrence and fate of siloxanes in wastewater treatment plant in Harbin,
      China.
AB  - The occurrence and fate of four cyclic (D3 to D6) and 10 linear (L5 to L14)
      siloxanes were investigated in influent and effluent wastewater, sludge from a
      wastewater treatment plant (WWTP), and surrounding air and soil within the WWTP
      in Harbin, Northeast China. The mean concentrations of total siloxanes in
      influent and effluent were 4780 and 997 ng/L and in excess sludge and aerobic
      sludge were 25.1 and 32.3 MUg/g dw, respectively. The concentrations in air and
      soil within the WWTP were 243 ng/m(3) and 4960 ng/g dw, respectively. A similar
      composition profile of siloxanes in influent and sludge suggests their same
      source. Seasonal variation with concentration was comprehensively studied. It was
      found that temperature and rainfall are the two important factors for the
      seasonal variation of siloxanes. Adsorption with sewage sludge was the major way
      for the removal of siloxanes during the municipal wastewater treatment process.
      Overall, on a daily basis, the mass loading of the Sigmasiloxanes into the WWTP,
      out of the WWTP with the effluent and sludge, were estimated to be 3.0, 0.6 and
      1.3 kg, respectively. In general, 21 % of siloxanes were discharged into the
      receiving body (Songhua River), 43 % of siloxanes were absorbed on sludge, and 36
      % of siloxanes were lost during the whole process of WWTP. 

PMID- 27023807
TI  - High nitrogen deposition in an agricultural ecosystem of Shaanxi, China.
AB  - Atmospheric nitrogen (N) deposition plays an important role in the global N
      cycle. Data for dry and wet N deposition in agricultural ecosystem of Shaanxi in
      China is still imperfect; in this study, we continuously measured concentrations
      and fluxes of dry N deposition from 2010 to 2013 in Yangling district of Shaanxi
      province and wet N deposition from 2010 to 2012. The average annual
      concentrations of NH3, NO2, HNO3, particulate ammonium, and nitrate (pNH4 (+) and
      pNO3 (-)) varied among 3.9-9.1, 6.6-8.0, 1.2-1.4, 3.1-4.3, and 3.3-4.8 MUg N m(
      3), respectively, with mean values of 6.0, 7.2, 1.3, 3.8, and 4.1 MUg N m(-3),
      respectively, during the entire monitoring period. The annual NH4 (+)-N and NO3 (
      )-N concentrations in precipitation ranged 3.9-4.3 and 2.8-3.4 mg N L(-1) with
      the mean values of 4.1 and 3.3 mg N L(-1). The NH4 (+)-N/NO3 (-)-N ratio in
      rainfall averaged 1.2. Dry N deposition flux was determined to be 19.2 kg N ha(
      1) year(-1) and the wet N deposition flux was 27.2 kg N ha(-1) year(-1). The
      amount of total atmospheric N deposition (dry plus wet) reached 46.4 kg N ha(-1)
      year(-1), in which dry deposition accounted 41 %. Gaseous N deposition comprised
      over 75 % of the dry deposition, and the proportion of oxidized N in dry
      deposition was equal to the reduced N. Therefore, the results suggest that more
      stringent regional air pollution control policies are required in the target area
      and that N deposition is an important nutrient resource from the atmosphere that
      must be taken into consideration in nutrient management planning of agricultural
      ecosystems. 

PMID- 27023808
TI  - Proposal for management and alkalinity transformation of bauxite residue in
      China.
AB  - Bauxite residue is a hazardous solid waste produced during the production of
      alumina. Its high alkalinity is a potential threat to the environment which may
      disrupt the surrounding ecological balance of its disposal areas. China is one of
      the major global producers of alumina and bauxite residue, but differences in
      alkalinity and associated chemistry exist between residues from China and those
      from other countries. A detailed understanding of the chemistry of bauxite
      residue remains the key to improving its management, both in terms of minimizing
      environmental impacts and reducing its alkaline properties. The nature of bauxite
      residue and the chemistry required for its transformation are still poorly
      understood. This review focuses on various transformation processes generated
      from the Bayer process, sintering process, and combined Bayer-sintering process
      in China. Problems associated with transformation mechanisms, technical methods,
      and relative merits of these technologies are reviewed, while current knowledge
      gaps and research priorities are recommended. Future research should focus on
      transformation chemistry and its associated mechanisms and for the development of
      a clear and economic process to reduce alkalinity and soda in bauxite residue. 

PMID- 27023809
TI  - The environmental fate of polybrominated diphenyl ethers (PBDEs) in western
      Taiwan and coastal waters: evaluation with a fugacity-based model.
AB  - The environmental fate of polybrominated diphenyl ethers (PBDEs), a group of
      flame retardants that are considered to be persistent organic pollutants (POPs),
      around the Zhuoshui River and Changhua County regions of Taiwan was assessed. An
      investigation into emissions, partitioning, and fate of selected PBDEs was
      conducted based on the equilibrium constant (EQC) fugacity model developed at
      Trent University, Canada. Emissions for congeners PBDE 47, PBDE 99, and PBDE 209
      to air (4.9-92 * 10(-3) kg/h), soil (0.91-17.4 * 10(-3) kg/h), and water (0.21
      4.04 * 10(-3) kg/h), were estimated by modifying previous models on PBDE emission
      rates by considering both industrial and domestic rates. It was found that
      fugacity modeling can give a reasonable estimation of the behavior, partitioning,
      and concentrations of PBDE congeners in and around Taiwan. Results indicate that
      PBDE congeners have a high affinity for partitioning into sediments then soils.
      As congener number decreases, the PBDEs then partition more readily into air. As
      the degree of bromination increases, congeners more readily partition to
      sediments. Sediments may then act as a long-term source of PBDEs which can be
      released back into the water column due to resuspension during storm events. 

PMID- 27023810
TI  - Construction and analysis of an intergeneric fusion from Pigmentiphaga sp. strain
      AAP-1 and Pseudomonas sp. CTN-4 for degrading acetamiprid and chlorothalonil.
AB  - Pseudomonas sp. CTN-4 degrades chlorothalonil (CTN) but not acetamiprid (AAP),
      and Pigmentiphaga sp. strain AAP-1 degrades AAP but not CTN. A functional strain,
      AC, was constructed through protoplast fusion of two parental strains
      (Pseudomonas sp. CTN-4 and Pigmentiphaga sp. strain AAP-1) in order to
      simultaneously improve the degradation efficiency of AAP and CTN. Fusant-AC with
      eight transfers on plates containing two antibiotics and CTN was obtained. For
      the purpose of identifying and confirming the genetic relationship between fusant
      AC and its parents, randomly amplified polymorphic DNA (RAPD), scanning electron
      microscopy (SEM), and 16S ribosomal DNA (rDNA) analysis were performed. In toto,
      RAPD fingerprint analysis produced 194 clear bands with 9 primers, which not only
      had bands in common with strains CTN-4 and AAP-1, but also had its own novel
      fusant-specific bands. The genetic similarity indices between fusant-AC and
      parental strains CTN-4 and AAP-1 were 0.40 and 0.69, respectively. The result of
      SEM indicated that the cell morphology of fusant-AC differed from both its
      parents. The fusant strain AC possesses a strong capability for AAP and CTN
      degradation. At AAP concentration (50-300 mg L(-1)), the degradation was achieved
      within 5 h. At the initial dose of 50 and 100 mg L(-1) CTN, the percentages
      reached 96 and 91 % over a 36-h incubation period. The present study indicates
      that the protoplast-fusion technique may have possible applications in
      environmental pollution control. 

PMID- 27023812
TI  - Causes of large Potamogeton crispus L. population increase in Xuanwu Lake.
AB  - In July 2005, the first outbreak of cyanobacterial blooms, dominated by
      Microcystis, occurred in Xuanwu Lake, Nanjing, upon which clay flocculation was
      adopted to control algal blooms. The cyanobacterial blooms were restrained, after
      which Potamogeton crispus appeared in November 2005 and spread rapidly in the
      whole lake. Since then, large populations of P. crispus have occurred in Xuanwu
      Lake annually in winter for the last 10 years. To determine the reasons for the
      occurrence of P. crispus populations in Xuanwu Lake during 2005-2006, water
      quality indices were monitored regularly. The data collected included dissolved
      oxygen, transparency, pH, total nitrogen, and total phosphorus content. Data
      analysis indicated that the transparency was improved by 179.5 % after clay
      flocculation, dissolved oxygen content increased by 24.1 %; total nitrogen and
      total phosphorus content decreased by 54.1 and 74.5 %, respectively, and pH fell
      from 9.1 to 8.7, all of which can be attributed to the emergency control measures
      for the cyanobacterial bloom. Data analysis also indicated that the improved
      water transparency after clay flocculation was the key factor in turion sprouting
      and seedling propagation of P. crispus. The ameliorative light intensity and
      favorable nutrient level all promoted the growth of seedlings of P. crispus and
      later quick colonization. It is suggested that ecological restoration of
      macrophytic and algal lakes be conducted by some physical or chemical means to
      improve transparency, reduce nutrient concentration, and adjust water pH, with
      the purpose of improving water quality for germination and growth of aquatic
      plants.

PMID- 27023811
TI  - Influence of zinc nanoparticles on survival of worms Eisenia fetida and taxonomic
      diversity of the gut microflora.
AB  - The study was conducted to examine the effect of zinc nanoparticles on survival
      of worms Eisenia fetida and composition of the gut microflora. Analysis of the
      survival data has shown that the introduction of high doses of the nanoparticles
      causes death of worms in the second group with 35 % mortality rate and activates
      protective mechanisms realized as mucous film. DNA from the worm guts was
      extracted and 16S metagenomic sequencing was fulfilled using MiSeq (Illumina).
      Regarding the gut microflora of worms in the control group, high diversity of
      microorganisms (303 OTUs) was noted. Most of those belong to the taxa Firmicutes
      (51.9 % of the total high-quality united reads), Proteobacteria (24.1 % of the
      total), and Actinobacteria (13.3 % of the total), which were represented by
      numerous species of gen. Clostridium (C. saccharobutylicum, C.
      saccharoperbutylacetonicum, C. beijerinckii), gen. Pseudomonas (P. hydrogenovora,
      P. aeruginosa, and P. putida), gen. Bacillus (B. megaterium, B. silvestris), gen.
      Cellulomonas (B. megaterium, B. silvestris), and other numerically smaller
      genera. Adding of zinc nanoparticles to the substrate decreased the diversity of
      bacteria (78 OTUs) as well as percentage of bacteria belonging to the taxon
      Firmicutes (-41.6 %) and increased the proportion of Proteobacteria due to growth
      in abundance of gen. Verminephrobacter (+46 %) and gen. Ochrobactrum (+19.5 %). 

PMID- 27023813
TI  - Diversity of endophytic Pseudomonas in Halimione portulacoides from metal(loid)
      polluted salt marshes.
AB  - Phytoremediation assisted by bacteria is seen as a promising alternative to
      reduce metal contamination in the environment. The main goal of this study was to
      characterize endophytic Pseudomonas isolated from Halimione portulacoides, a
      metal-accumulator plant, in salt marshes contaminated with metal(loid)s.
      Phylogenetic analysis based on 16S rRNA and gyrB genes showed that isolates
      affiliated with P. sabulinigri (n = 16), P. koreensis (n = 10), P. simiae (n =
      5), P. seleniipraecipitans (n = 2), P. guineae (n = 2), P. migulae (n = 1), P.
      fragi (n = 1), P. xanthomarina (n = 1), and Pseudomonas sp. (n = 1). Most of
      these species have never been described as endophytic. The majority of the
      isolates were resistant to three or more metal(loid)s. Antibiotic resistance was
      frequent among the isolates but most likely related to species-intrinsic
      features. Common acquired antibiotic resistance genes and integrons were not
      detected. Plasmids were detected in 43.6 % of the isolates. Isolates that
      affiliated with different species shared the same plasmid profile but attempts to
      transfer metal resistance to receptor strains were not successful. Phosphate
      solubilization and IAA production were the most prevalent plant growth promoting
      traits, and 20 % of the isolates showed activity against phytopathogenic
      bacteria. Most isolates produced four or more extracellular enzymes. Preliminary
      results showed that two selected isolates promote Arabidopsis thaliana root
      elongation. Results highlight the diversity of endophytic Pseudomonas in H.
      portulacoides from contaminated sites and their potential to assist
      phytoremediation by acting as plant growth promoters and as environmental
      detoxifiers. 

PMID- 27023814
TI  - Microbial degradation of endosulfan in contaminated soil with the elution of
      surfactants.
AB  - In this work, an endosulfan-degrading strain was isolated from the aged soil
      contaminated by endosulfan, and identified as Ochrobactrum sp. EB-4 by 16S rDNA
      sequence analysis. The microbial degradation characteristics of endosulfan in
      three eluents (Tween 80 + SDS, Tween 80 + Na2SiO3, Tween 80 + SDS + Na2SiO3) were
      investigated. The results showed that the degradation percents of alpha-, beta
      endosulfan in the three eluents were 86.83 %~92.91 % and 88.90 %~93.94 % in 15
      days, respectively. The degradation process can be well described by the first
      order kinetic model, and the half-times of alpha-endosulfan in eluent 1~eluent 3
      were 3.83, 5.29, and 4.53 days, while those of beta-endosulfan were 3.35, 4.50
      and 3.79 days, respectively. The endosulfan diol and endosulfan sulfate as main
      metabolites were detected, and the former can be further degraded by this strain,
      which revealed that the simultaneously happened hydrolysis and oxidation
      reactions were the main degradation processes, and dominated by hydrolysis
      reaction. After 5 days of washing with the eluents, 56.00~84.33 % of alpha
      endosulfan, and 46.49~68.56 % of beta-endosulfan in soil were eluted,
      respectively, and can be entirely biodegraded in 12 days, which indicated that
      the microbial degradation was the rate-determining step. 

PMID- 27023815
TI  - Reproductive and developmental toxicity of the herbicide Betanal(r) Expert and
      corresponding active ingredients to Daphnia spp.
AB  - The commercial herbicide formulation Betanal(r) Expert and its active ingredients
      (a.i.s) ethofumesate, phenmedipham and desmedipham were focused in this study.
      Following questions yielding from a previous study, an in-depth analysis of the
      reproductive toxicity of the pesticide was made. Long-term exposures of Daphnia
      magna and Daphnia longispina to Betanal(r) Expert, to each a.i. and to a
      customised mixture matching the a.i.s ratio within the commercial formulation
      were carried out, and deleterious effects in the offspring were recorded. This
      intended to clarify whether (1) the tested compounds induce reproductive injury;
      (2) there is interspecific variation in daphnids tolerance to the compounds; (3)
      there is an interaction between chemicals in combined treatments; and (4) the so
      called inert ingredients added to the commercial formulation contribute to the
      toxicity of the herbicide. Generally, developmental impair was observed in both
      species (egg abortion and release of undeveloped embryos or dead offspring) at
      concentrations of any of the a.i.s below 1 mg L(-1). Ethofumesate was invariably
      the least toxic pesticide, and D. magna tended to be of slightly higher
      sensitivity to the exposures compared to D. longispina. Joint exposures indicated
      that the a.i.s can interact, inducing more than and less than additive effects
      for Betanal(r) Expert and the customised a.i. mixture, respectively. This
      indicates that inert ingredients co-formulating the commercial pesticide (which
      are absent from the customised a.i. mixture) actually contribute to its overall
      toxicity. This study constitutes an add-on to the discussion on the
      ecotoxicological framework required for authorisation of pesticide trade and
      usage. The results support the need to consider test species, long-term hazardous
      potential and toxicity of commercial formulations rather than solely that of
      active ingredients, as relevant variables in pesticide regulation. 

PMID- 27023816
TI  - Degradation of artificial sweeteners via direct and indirect photochemical
      reactions.
AB  - We studied the direct and indirect photochemical reactivity of artificial
      sweeteners acesulfame, saccharin, cyclamic acid and sucralose in environm entally
      relevant dilute aqueous solutions. Aqueous solutions of sweeteners were
      irradiated with simulated solar radiation (>290 nm; 96 and 168 h) or ultraviolet
      radiation (UVR; up to 24 h) for assessing photochemical reactions in surface
      waters or in water treatment, respectively. The sweeteners were dissolved in
      deionised water for examination of direct photochemical reactions. Direct
      photochemical reactions degraded all sweeteners under UVR but only acesulfame
      under simulated solar radiation. Acesulfame was degraded over three orders of
      magnitude faster than the other sweeteners. For examining indirect photochemical
      reactions, the sweeteners were dissolved in surface waters with indigenous
      dissolved organic matter or irradiated with aqueous solutions of nitrate (1 mg
      N/L) and ferric iron (2.8 mg Fe/L) introduced as sensitizers. Iron enhanced the
      photodegradation rates but nitrate and dissolved organic matter did not. UVR
      transformed acesulfame into at least three products: iso-acesulfame, hydroxylated
      acesulfame and hydroxypropanyl sulfate. Photolytic half-life was one year for
      acesulfame and more than several years for the other sweeteners in surface waters
      under solar radiation. Our study shows that the photochemical reactivity of
      commonly used artificial sweeteners is variable: acesulfame may be sensitive to
      photodegradation in surface waters, while saccharin, cyclamic acid and sucralose
      degrade very slowly even under the energetic UVR commonly used in water
      treatment. 

PMID- 27023817
TI  - Degradation of chlorinated organic solvents in aqueous percarbonate system using
      zeolite supported nano zero valent iron (Z-nZVI) composite.
AB  - Chlorinated organic solvents (COSs) are extensively detected in contaminated soil
      and groundwater that pose long-term threats to human life and environment. In
      order to degrade COSs effectively, a novel catalytic composite of natural zeolite
      supported nano zero valent iron (Z-nZVI) was synthesized in this study. The
      performance of Z-nZVI-catalyzed sodium percarbonate (SPC) in a heterogeneous
      Fenton-like system was investigated for the degradation of COSs such as 1,1,1
      trichloroethane (1,1,1-TCA) and trichloroethylene (TCE). The surface
      characteristics and morphology of the Z-nZVI composite were tested using scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM). Total pore
      volume, specific surface area, and pore size of the natural zeolite and the Z
      nZVI composite were measured using Brunauer-Emmett-Teller (BET) method. SEM and
      TEM analysis showed significant elimination of aggregation and well dispersion of
      iron nano particles on the framework of natural zeolite. The BET N2 measurement
      analysis indicated that the surface area of the Z-nZVI composite was 72.3 m(2)/g,
      much larger than that of the natural zeolite (0.61 m(2)/g). For the contaminant
      analysis, the samples were extracted with n-hexane and analyzed through gas
      chromatograph. The degradation of 1,1,1-TCA and TCE in the Z-nZVI-catalyzed
      percarbonate system were 48 and 39 % respectively, while strong augmentation was
      observed up to 83 and 99 %, respectively, by adding the reducing agent (RA),
      hydroxyl amine (NH2OH*HCl). Probe tests validated the presence of OH(?) and O2 (?
      ) which were responsible for 1,1,1-TCA and TCE degradation, whereas both free
      radicals were strengthened with the addition of RA. In conclusion, the Z-nZVI/SPC
      oxidation with reducing agent shows potential technique for degradation of
      groundwater contaminated by 1,1,1-TCA and TCE. 

PMID- 27023818
TI  - The role of roots in the accumulation and removal of cadmium by the aquatic plant
      Hydrilla verticillata.
AB  - Aquatic macrophytes can absorb heavy metals either from sediments via the root
      system, from the water phase by leaves, or from both sources. In this study,
      cadmium accumulation and distribution in the aquatic plant Hydrilla verticillata
      were investigated, with a focus on the role of roots. Results showed that leaves
      of H. verticillata had a higher Cd concentration than roots when intact plants
      were grown in sediments and solutions containing Cd. Cadmium can significantly
      decrease the leaf chlorophyll content, and the leaves of intact plants with roots
      had lower chlorophyll contents than the leaves of detached ones without roots due
      to the transfer effect of roots. The majority of the Cd accumulated in leaves of
      H. verticillata was bound to the cell walls. When roots were submerged in a
      solution containing Cd, with shoots in a control solution without Cd, the Cd
      concentrations in leaves were considerably lower than in roots. In contrast, Cd
      was almost undetectable in roots when the shoots were submerged in a solution
      containing Cd, with roots in the control solution. Compared to the leaves and
      stems of detached shoots without roots, the concentrations of Cd were much higher
      in the leaves and stems of intact plants with roots. It is suggested that the
      roots of intact plants absorb Cd and transfer it to leaves and that more Cd is
      removed from the solution by intact plants. 

PMID- 27023819
TI  - Influence of stocking density on the vermicomposting of an effluent treatment
      plant sludge amended with cow dung.
AB  - This paper reports the effect of earthworm population density on the
      vermicomposting of effluent treatment plant sludge of a bakery industry. Four
      waste mixtures containing 0, 10, 20, and 30 % sludge along with cow dung with
      five different worm population densities were established for 14 weeks under
      controlled moisture and temperature conditions. The results showed that average
      worm biomass, growth and cocoon production were lesser at higher population
      densities. Sexual maturity was attained in 3rd to 5th week in all waste mixtures.
      Worm growth was inversely related to worm population density in the waste
      mixture. Results also indicated that lower worm population is favorable to worm
      biomass production. On the other hand, mineralization and stabilization of the
      waste mixtures were more at higher worm populations. 

PMID- 27023820
TI  - Water age prediction and its potential impacts on water quality using a
      hydrodynamic model for Poyang Lake, China.
AB  - The water quality in Poyang Lake, the largest freshwater lake in China, has
      deteriorated steadily in recent years and local governments have made efforts to
      manage the potential eutrophication. In order to investigate the transport and
      retention processes of dissolved substances, the hydrodynamic model,
      Environmental Fluid Dynamics Code (EFDC) was applied by using the concept of
      water age. The simulated results showed agreement with the measured water level,
      discharge, and inundation area. The water age in Poyang Lake was significantly
      influenced by the variations of hydrological conditions. The annual analysis
      revealed that the largest averaged water age was observed during the wet year
      (2010) with 28.4 days at Hukou, the junction of the Yangtze River and Poyang
      Lake. In the normal season (April), the youngest age with 9.1 days was found. The
      spatial distribution of water quality derived from the remote sensing images
      suggested that a higher chlorophyll-a concentration, lower turbidity, and smaller
      water age in the eastern area of Poyang Lake might threaten the regional aquatic
      health. The particle tracking simulation reproduced the trajectories of the
      dissolved substances, indicating that the water mass with greater nutrient
      loading would further lead to potential environmental problems in the east lake.
      Moreover, the water transfer ability would be weakened due to dam (Poyang
      Project) construction resulting in the rising water levels in periods of
      regulation. Generally, this study quantified an indicative transport timescale,
      which could help to better understand the complex hydrodynamic processes and
      manage wetland ecosystems similar to Poyang Lake. 

PMID- 27023821
TI  - USPIO assisting degradation of MXC by host/guest-type immobilized laccase in AOT
      reverse micelle system.
AB  - The laccase and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO)
      have been assembled inside the tubular mesoporous silica via co-adsorption
      technology to prepare host/guest-type immobilized laccase, which is applied to
      degrade methoxychlor (MXC) in aqueous and reverse micelle environments. The
      effects of various parameters on degradation of MXC were studied. Under the
      optimum conditions, the degradation rate could reach maximum value of 45.6 % and
      remain at 20.8 % after seven cycles. Moreover, the addition of small molecular
      compound 2, 2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) to the system could
      greatly improve the degradation efficiency. The MXC degradation process is a
      first-order reaction, and the activation energy of MXC degradation catalyzed by
      immobilized laccase (41.46 kJ mol(-1)) is relatively lower than that catalyzed by
      free laccase (44.91 kJ mol(-1)). Based on the degradation products measured by
      gas chromatograph-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR),
      the degradation mechanism of MXC has also been proposed. 

PMID- 27023822
TI  - Multibiomarker toxicity characterization of uranium mine drainages to the fish
      Carassius auratus.
AB  - The release of acidic effluents, naturally enriched in metals and radionuclides,
      is the main legacy of uranium mines. Generally, metals dissolved by these acidic
      effluents can cause significant alterations in exposed organisms, with distinct
      toxicological outcomes. In this study, 72 individuals of the freshwater fish
      species Carassius auratus were exposed in situ for different periods (8, 16, 24,
      and 48 h) to water from a pond (treatment pond (TP)) with a chemically treated
      effluent and a reference pond (PRP), in the vicinity of the Cunha Baixa uranium
      mine (Portugal). Comparing the water of the two ponds, the PRP pond was
      characterized by higher pH and oxygen values and lower conductivity and hardness
      values. Regarding total metal concentrations, among others, magnesium (56,000
      MUg/L), sodium (17,400 MUg/L), zinc (86 MUg/L), manganese (6340 MUg/L), and
      uranium (1380 MUg/L) concentrations in the TP pond were above the values obtained
      for the PRP pond. The values of manganese and uranium exceeded the values of
      quality criteria established for surface waters for cyprinids and for irrigation
      purposes. After exposure to pond water, significant differences were recorded for
      several biomarkers: (i) between ponds for acetylcholinesterase (AChE) with higher
      activities for animals from the PRP and glutathione-S-transferase (GST)
      activities that were particularly enhanced in animals from the TP pond; (ii)
      between ponds and exposure periods for lactate dehydrogenase (LDH) activity,
      since organisms from PRP pond presented always higher values than those from the
      TP pond, and among these, organisms exposed for the longer period presented a
      further depression in LDH activity; and (iii) between exposure periods for
      erythrocyte micronucleus. GSTs and LDH were the most sensitive biomarkers within
      the timeframe of the in situ assay performed. Despite the alleged efficacy of the
      chemical treatment (evidenced by a significantly lower pH), some metals persisted
      in the treated effluent (TP pond), potentially contributing to the induction of
      oxidative stress or increased conjugation metabolic activity in fish. 

PMID- 27023824
TI  - Radiologic and Clinical Evaluation 12 Months after Anterior Cervical Diskectomy
      and Dynamic Stabilization of the Segment with Dynamic Cervical Implant.
AB  - Background Anterior cervical diskectomy (ACD) is an established therapy for
      degenerative cervical radiculopathy and myelopathy. Controversy remains regarding
      the dynamic or rigid stabilization of the segment. Methods We studied our first
      31 patients treated with ACD plus the Dynamic Cervical Implant (DCI) as an
      alternative to fusion or to arthroplasty, treated between February 2009 and 2011.
      Radiologic data were collected before and 12 months after surgery. Clinical
      results were documented 12 months after surgery. The radiologic analysis focused
      on the mobility of the segment, position of the implant, amount of preoperative
      osteochondrosis, and the development of heterotopic ossifications (HOs) after 1
      year. Results At the 1-year follow-up after DCI implantation, there was quite a
      high fusion rate (23%); however, the formation of HOs was comparable with that of
      arthroplasty. Fusion could not be predicted by viewing the degree of disk
      degeneration on preoperative magnetic resonance imaging studies and had no
      negative impact on the clinical outcome. Conclusion As an alternative to
      arthroplasty, DCI does maintain some flexion-extension mobility after 1 year in
      77% of our cases.

PMID- 27023825
TI  - One-Year Prospective Evaluation of the Technique of Percutaneous Cortical Bone
      Trajectory Spondylodesis in Comparison with Percutaneous Pedicle Screw Fixation:
      A Preliminary Report with Technical Note.
AB  - Background and Objective Cortical bone trajectory (CBT) spondylodesis is a novel
      screw fixation method in which screws are inserted through the pedicle in a
      caudal-medial to cephalad-lateral direction, providing a similar or more rigid
      spinal fixation compared with traditional pedicle screws. However, the
      traditional CBT technique requires invasive detaching and opening of the
      paraspinal muscle. In a small clinical prospective study we introduced a
      percutaneous CBT fixation technique by modifying the percutaneous pedicle screw
      (PPS) technique and evaluated the short-term outcome. Materials and Methods We
      enrolled 40 patients with lower back pain (LBP) and limb r;adicular pain with a
      diagnosis of spondylolisthesis who underwent transforaminal lumbar interbody
      fusion surgery. The patients were divided into two groups according to screw
      trajectory: the percutaneous CBT (pCBT) and the traditional PPS arms (20 patients
      in each). A consecutive group of 20 patients underwent traditional PPS, and the
      other underwent pCBT; dorsal spondylodesis was combined with transforaminal
      lumbar interbody fusion (TLIF) in both groups. Perioperative data such as
      operative time, blood loss, duration of fluoroscopy, and total incision length
      were investigated. Postoperative outcomes were evaluated using the visual analog
      scale (VAS) for LBP and leg pain at baseline, 1, 6, and 12 months. A p value <
      0.05 was considered statistically significant. Results We observed no significant
      disadvantages in pCBT patients in perioperative and postoperative data compared
      with the PPS group. There were no complications. The pCBT patients showed a
      significantly shorter total incision length (p < 0.01) with a significantly
      shorter duration of fluoroscopy (p < 0.05). The postoperative VAS score was
      significantly improved in the pCBT group, especially 6 months after the surgery
      (p < 0.05). Conclusion The pCBT spondylodesis provided an outcome comparable with
      PPS fixation with a tendency for improvement 1 year postsurgery. This technique
      can be used in appropriate cases, combined with lumbar interbody fusion.

PMID- 27023826
TI  - Long-Term Catheterization of the Intestinal Lymph Trunk and Collection of Lymph
      in Neonatal Pigs.
AB  - Catheterization of the intestinal lymph trunk in neonatal pigs is a technique
      allowing for the long-term collection of large quantities of intestinal (central)
      efferent lymph. Importantly, the collection of central lymph from the intestine
      enables researchers to study both the mechanisms and lipid constitutes associated
      with lipid metabolism, intestinal inflammation and cancer metastasis, as well as
      cells involved in immune function and immunosurveillance. A ventral mid-line
      surgical approach permits excellent surgical exposure to the cranial abdomen and
      relatively easy access to the intestinal lymph trunk vessel that lies near the
      pancreas and the right ventral segment of the portal vein underneath the visceral
      aspect of the right liver lobe. The vessel is meticulously dissected and released
      from the surrounding fascia and then dilated with sutures allowing for insertion
      and subsequent securing of the catheter into the vessel. The catheter is
      exteriorized and approximately 1 L/24 hr of lymph is collected over a 7 day
      period. While this technique enables the collection of large quantities of
      central lymph over an extended period of time, the success depends on careful
      surgical dissection, tissue handling and close attention to proper surgical
      technique. This is particularly important with surgeries in young animals as the
      lymph vessels can easily tear, potentially leading to surgical and experimental
      failure. The video demonstrates an excellent surgical technique for the
      collection of intestinal lymph. 

PMID- 27023827
TI  - Clinical presentation and management of an Aruban rattlesnake bite in the
      Netherlands.
AB  - Bites by Aruban Rattlesnake (Crotalus durissus unicolor) are rare and not known
      to induce severe envenomations. Here, we present a case of a 57 year-old man
      bitten by his pet Aruban Rattlesnake (Crotalus durissus unicolor). He was
      admitted to hospital within 15 min. Three and a half hours later his fibrinogen
      concentration decreased to 0.6 g/L (normal: 2.0-4.0). Nine hours post-bite, he
      was treated with polyvalent snake antivenom covering Crotalus durissus. Three
      hours later his fibrinogen became undetectable while at that time clotting times
      were prolonged (PT 38.7 s (normal: 12.5-14.5) and aPTT 40 s (normal: 25-35)). His
      platelet count remained within normal limits. Creatine kinase (CK) concentrations
      reached a maximum of 1868 U/L (normal: <200) 16 h post-bite. After a second
      antivenom dose, 10.5 h after the first antivenom administration, clotting times
      returned to normal. Fibrinogen was restored to normal within three days. He was
      discharged from hospital on day five. In conclusion, administration of polyvalent
      snake antivenom covering Crotalus durissus snakebites shows cross-neutralization
      and is effective in the treatment of patients bitten by Crotalus durissus
      unicolor. 

PMID- 27023823
TI  - Status of hormones and painkillers in wastewater effluents across several
      European states-considerations for the EU watch list concerning estradiols and
      diclofenac.
AB  - Present technologies for wastewater treatment do not sufficiently address the
      increasing pollution situation of receiving water bodies, especially with the
      growing use of personal care products and pharmaceuticals (PPCP) in the private
      household and health sector. The relevance of addressing this problem of organic
      pollutants was taken into account by the Directive 2013/39/EU that introduced (i)
      the quality evaluation of aquatic compartments, (ii) the polluter pays principle,
      (iii) the need for innovative and affordable wastewater treatment technologies,
      and (iv) the identification of pollution causes including a list of principal
      compounds to be monitored. In addition, a watch list of 10 other substances was
      recently defined by Decision 2015/495 on March 20, 2015. This list contains,
      among several recalcitrant chemicals, the painkiller diclofenac and the hormones
      17beta-estradiol and 17alpha-ethinylestradiol. Although some modern approaches
      for their removal exist, such as advanced oxidation processes (AOPs),
      retrofitting most wastewater treatment plants with AOPs will not be acceptable as
      consistent investment at reasonable operational cost. Additionally, by-product
      and transformation product formation has to be considered. The same is true for
      membrane-based technologies (nanofiltration, reversed osmosis) despite of the
      incredible progress that has been made during recent years, because these systems
      lead to higher operation costs (mainly due to higher energy consumption) so that
      the majority of communities will not easily accept them. Advanced technologies in
      wastewater treatment like membrane bioreactors (MBR) that integrate biological
      degradation of organic matter with membrane filtration have proven a more
      complete elimination of emerging pollutants in a rather cost- and labor-intensive
      technology. Still, most of the presently applied methods are incapable of
      removing critical compounds completely. In this opinion paper, the state of the
      art of European WWTPs is reflected, and capacities of single methods are
      described. Furthermore, the need for analytical standards, risk assessment, and
      economic planning is stressed. The survey results in the conclusion that
      combinations of different conventional and advanced technologies including
      biological and plant-based strategies seem to be most promising to solve the
      burning problem of polluting our environment with hazardous emerging xenobiotics.

PMID- 27023828
TI  - Effects of UV Rays and Thymol/Thymus vulgaris L. Extract in an ex vivo Human Skin
      Model: Morphological and Genotoxicological Assessment.
AB  - Ultraviolet (UV) radiation is the major environmental factor affecting functions
      of the skin. Compounds rich in polyphenols, such as Thymus vulgaris leaf extract
      and thymol, have been proposed for the prevention of UV-induced skin damage. We
      compared the acute effects induced by UVA and UVB rays on epidermal morphology
      and proliferation, cytotoxicity, and genotoxicity. Normal human skin explants
      were obtained from young healthy women (n = 7) after informed consent and
      cultured at the air-liquid interface overnight. After 24 h, the samples were
      divided in 2 groups: the former exposed to UVA (16 or 24 J/cm2) and the latter
      irradiated with UVB (0.24 or 0.72 J/cm2). One hour after the end of irradiation,
      supernatants were collected for evaluation of the lactate dehydrogenase activity.
      Twenty-four hours after UVB exposure, biopsies were processed for light and
      transmission electron microscopy analysis, proliferation, cytotoxicity, and
      genotoxicity. UVB and UVA rays induced early inhibition of cell proliferation and
      DNA damage compared to controls. In particular, UVB rays were always more
      cytotoxic and genotoxic than UVA ones. For this reason, we evaluated the effect
      of either T. vulgaris L. extract (1.82 ug/ml) or thymol (1 ug/ml) on all samples
      treated for 1 h before UVB irradiation. While Thymus had a protective action for
      all of the endpoints evaluated, the action of the extract was less pronounced on
      epidermal proliferation and morphological features. The results presented in this
      study could be the basis for investigating the mechanism of thymol and T.
      vulgaris L. extract against the damage induced by UV radiation. 

PMID- 27023829
TI  - Retraction: Isolation of Immune Cells from Primary Tumors.
AB  - The article Isolation of Immune Cells from Primary Tumors, has been retracted at
      the request of the corresponding author due to concerns regarding the validity of
      the data presented in the article. 

PMID- 27023830
TI  - Ratiometric Imaging of Extracellular pH in Dental Biofilms.
AB  - The pH in bacterial biofilms on teeth is of central importance for dental caries,
      a disease with a high worldwide prevalence. Nutrients and metabolites are not
      distributed evenly in dental biofilms. A complex interplay of sorption to and
      reaction with organic matter in the biofilm reduces the diffusion paths of
      solutes and creates steep gradients of reactive molecules, including organic
      acids, across the biofilm. Quantitative fluorescent microscopic methods, such as
      fluorescence life time imaging or pH ratiometry, can be employed to visualize pH
      in different microenvironments of dental biofilms. pH ratiometry exploits a pH
      dependent shift in the fluorescent emission of pH-sensitive dyes. Calculation of
      the emission ratio at two different wavelengths allows determining local pH in
      microscopic images, irrespective of the concentration of the dye. Contrary to
      microelectrodes the technique allows monitoring both vertical and horizontal pH
      gradients in real-time without mechanically disturbing the biofilm. However, care
      must be taken to differentiate accurately between extra- and intracellular
      compartments of the biofilm. Here, the ratiometric dye, seminaphthorhodafluor-4F
      5-(and-6) carboxylic acid (C-SNARF-4) is employed to monitor extracellular pH in
      in vivo grown dental biofilms of unknown species composition. Upon exposure to
      glucose the dye is up-concentrated inside all bacterial cells in the biofilms; it
      is thus used both as a universal bacterial stain and as a marker of extracellular
      pH. After confocal microscopic image acquisition, the bacterial biomass is
      removed from all pictures using digital image analysis software, which permits to
      exclusively calculate extracellular pH. pH ratiometry with the ratiometric dye is
      well-suited to study extracellular pH in thin biofilms of up to 75 um thickness,
      but is limited to the pH range between 4.5 and 7.0. 

PMID- 27023831
TI  - Grinding and polishing instead of sectioning for the tissue samples with a graft:
      Implications for light and electron microscopy.
AB  - A broad use of the graft replacement requires a detailed investigation of the
      host-graft interaction, including both histological examination and electron
      microscopy. A high quality sectioning of the host tissue with a graft seems to be
      complicated; in addition, it is difficult to examine the same tissue area by both
      of the mentioned microscopy techniques. To solve these problems, we developed a
      new technique of epoxy resin embedding with the further grinding, polishing, and
      staining. Graft-containing tissues prepared by grinding and polishing preserved
      their structure; however, sectioning frequently required the explantation of the
      graft and led to tissue disintegration. Moreover, stained samples prepared by
      grinding and polishing may then be assessed by both light microscopy and
      backscattered scanning electron microscopy. Therefore, grinding and polishing
      outperform sectioning when applied to the tissues with a graft. 

PMID- 27023832
TI  - High speed indentation measures by FV, QI and QNM introduce a new understanding
      of bionanomechanical experiments.
AB  - Structural and mechanical mapping at the nanoscale by novel high-speed
      multiparametric Quantitative Imaging (QI) and PeakForce Quantitative
      Nanomechanical Mapping (PF-QNM) AFM modes was compared to the classical Force
      Volume (FV) mapping for the case of living Pseudomonas aeruginosa bacterial
      cells. QI and PF-QNM modes give results consistent with FV for the whole cells in
      terms of morphology and elastic modulus, while providing higher resolution and
      shorter acquisition time. As an important complement, the influence of scanning
      parameters on elastic modulus values was explored for small 0.2(2)MUm(2) central
      area on top of cells. The modulus decreases with the indentation depth due to the
      effect of the hard cell wall, while it increases vs. tip oscillation frequency,
      displaying viscoelastic behaviour of the living bacterial cells. The ability of
      different AFM modes to follow correctly the bacteria viscoelastic behaviour at
      high oscillation frequency was tested. 

PMID- 27023833
TI  - Travel-Associated Zika Virus Disease Cases Among U.S. Residents--United States,
      January 2015-February 2016.
AB  - Zika virus is an emerging mosquito-borne flavivirus. Recent outbreaks of Zika
      virus disease in the Pacific Islands and the Region of the Americas have
      identified new modes of transmission and clinical manifestations, including
      adverse pregnancy outcomes. However, data on the epidemiology and clinical
      findings of laboratory-confirmed Zika virus disease remain limited. During
      January 1, 2015-February 26, 2016, a total of 116 residents of 33 U.S. states and
      the District of Columbia had laboratory evidence of recent Zika virus infection
      based on testing performed at CDC. Cases include one congenital infection and 115
      persons who reported recent travel to areas with active Zika virus transmission
      (n = 110) or sexual contact with such a traveler (n = 5). All 115 patients had
      clinical illness, with the most common signs and symptoms being rash (98%; n =
      113), fever (82%; 94), and arthralgia (66%; 76). Health care providers should
      educate patients, particularly pregnant women, about the risks for, and measures
      to prevent, infection with Zika virus and other mosquito-borne viruses. Zika
      virus disease should be considered in patients with acute onset of fever, rash,
      arthralgia, or conjunctivitis, who traveled to areas with ongoing Zika virus
      transmission (http://www.cdc.gov/zika/geo/index.html) or who had unprotected sex
      with a person who traveled to one of those areas and developed compatible
      symptoms within 2 weeks of returning.

PMID- 27023835
TI  - Cardiovascular disease in chronic kidney disease in 2015.
AB  - PURPOSE OF REVIEW: Chronic kidney disease (CKD) is strongly linked to premature
      cardiovascular disease, which is the leading cause of death before end-stage
      renal disease in these patients. Herein, we review recent literature from 2014 to
      2015 that has advanced our understanding of cardiovascular outcomes in patients
      with advanced and/or progressive CKD. RECENT FINDINGS: We focus on new data
      describing the mechanisms of cardiac death in patients with CKD as well as the
      novel associations between cardiac events and the competing risks of end-stage
      renal disease and pre-end-stage renal disease death. We review new controversies
      in multivessel revascularization of complex coronary artery disease in CKD and,
      finally, the treatment of systolic heart failure in advanced CKD, including the
      use of implantable defibrillator therapy. SUMMARY: Marked advances in the
      understanding of cardiovascular disease in CKD have occurred in the past year,
      namely from retrospective and registry data. Although exciting, these recent
      studies highlight the urgent need for randomized control trials to guide
      therapeutic decisions.

PMID- 27023834
TI  - New approaches in renal microscopy: volumetric imaging and superresolution
      microscopy.
AB  - PURPOSE OF REVIEW: Histologic and electron microscopic analysis of the kidney has
      provided tremendous insight into structures such as the glomerulus and nephron.
      Recent advances in imaging, such as deep volumetric approaches and
      superresolution microscopy, have the capacity to dramatically enhance our current
      understanding of the structure and function of the kidney. Volumetric imaging can
      generate images millimeters below the surface of the intact kidney.
      Superresolution microscopy breaks the diffraction barrier inherent in traditional
      light microscopy, enabling the visualization of fine structures. Here, we
      describe new approaches to deep volumetric and superresolution microscopy of the
      kidney. RECENT FINDINGS: Rapid advances in lasers, microscopic objectives, and
      tissue preparation have transformed our ability to deep volumetric image the
      kidney. Innovations in sample preparation have allowed for superresolution
      imaging with electron microscopy correlation, providing unprecedented insight
      into the structures within the glomerulus. SUMMARY: Technological advances in
      imaging have revolutionized our capacity to image both large volumes of tissue
      and the finest structural details of a cell. These new advances have the
      potential to provide additional profound observations into the normal and
      pathologic functions of the kidney.

PMID- 27023836
TI  - The impact of hypoxia on nephrogenesis.
AB  - PURPOSE OF REVIEW: Kidney development depends on outgrowth of the ureteric bud
      into the metanephric mesenchyme. The number of ureteric bud branching events
      determines the final number of nephrons, which correlates inversely with the risk
      for development of chronic kidney disease and arterial hypertension during
      lifetime. The purpose of this review is to highlight the influence of oxygen on
      nephrogenesis and to describe cellular mechanisms by which hypoxia can impair
      nephron formation. RECENT FINDINGS: Although kidney development normally takes
      place under hypoxic conditions, nephrogenesis is impaired when oxygen
      availability falls below the usual range. Hypoxia-inducible factors (HIF) play an
      important role in linking low oxygen concentrations to the biology of nephron
      formation, but their effect appears to be cell type dependent. In ureteric bud
      cells, HIF stimulates tubulogenesis, whereas HIF stabilization in cells of the
      metanephric mesenchyme results in secretion of growth factors, including vascular
      endothelial growth factor A, which in aggregate inhibit ureteric bud branching.
      The balance between pro and antibranching effects may be altered in various ways,
      but the inhibitory effect usually seems to predominate under reduced oxygen
      concentrations, explaining how intrauterine hypoxia can lead to low nephron
      numbers. SUMMARY: Oxygen availability has a complex influence on nephrogenesis.
      Oxygen concentrations outside an optimal low range may affect nephron endowment.
      Associations between placental insufficiency and increased risk for chronic
      kidney disease and arterial hypertension during later life may to a large extent
      be due to direct effects of reduced oxygen supply to the metanephric mesenchyme
      and mediated through the HIF pathway.

PMID- 27023837
TI  - Predicting acute kidney injury prognosis.
AB  - PURPOSE OF REVIEW: The incidence of acute kidney injury has been steadily
      increasing. The development of any degree of kidney injury is associated with
      worse outcomes. Therefore, the ability to risk stratify patients and to predict
      prognosis is essential to properly educate the patient and family, appropriately
      utilize healthcare resources, and provide therapeutic interventions that may
      improve outcomes. RECENT FINDINGS: Numerous biomarkers and clinical prediction
      models have been developed that improve our ability to predict which patients
      will progress to higher stages of chronic kidney disease, require dialysis, or
      survive. The integration of biomarkers in predictive models will likely provide
      the best information. Further investigation will be required to validate the
      utility of these tools. SUMMARY: Early risk stratification for acute kidney
      injury can aid clinical decision making. The use of various biomarkers and
      predictive clinical models will improve the ability to appropriately utilize
      resources and provide useful prognostic information.

PMID- 27023839
TI  - The evolving science of apolipoprotein-L1 and kidney disease.
AB  - PURPOSE OF REVIEW: There are evolving epidemiological and biological data to
      support an association between the gene encoding apolipoprotein-L1 (APOL1) and
      progressive chronic kidney disease (CKD) among African-Americans. RECENT
      FINDINGS: Individuals with two APOL1 risk alleles are at greater risk of incident
      albuminuria, CKD, and progression to end-stage renal disease despite optimal
      blood pressure management and use of angiotensin-converting enzyme inhibitors.
      These variants also appear to influence outcomes in donor and recipients in
      kidney transplantation. Recent studies have also variably shown a potential role
      of APOL1 variants in cardiovascular disease. A number of studies have addressed
      genetic and environmental factors such as HIV but most do not modify the course
      of APOL1-related kidney disease. Although the exact mechanism remains unclear,
      functional studies have demonstrated the effect of APOL1 and related protein on
      innate immunity and cytotoxicity. SUMMARY: APOL1 is an important genetic risk
      factor for kidney disease among African-Americans. With approximately one in 10
      African-Americans at risk, further studies are warranted to identify underlying
      biological mechanisms and other potential modifiers leading to CKD. Moreover,
      studies that clarify the association of APOL1 variants with cardiovascular
      disease, independent of CKD, are also needed.

PMID- 27023838
TI  - Kidney tubules: intertubular, vascular, and glomerular cross-talk.
AB  - PURPOSE OF REVIEW: The kidney mediates the excretion or conservation of water and
      electrolytes in the face of changing fluid and salt intake and losses. To
      ultrafilter and reabsorb the exact quantities of free water and salts to maintain
      euvolemia a range of endocrine, paracrine, and hormonal signaling systems have
      evolved linking the tubules, capillaries, glomeruli, arterioles, and other
      intrinsic cells of the kidney. Our understanding of these systems remains
      incomplete. RECENT FINDINGS: Recent work has provided new insights into the
      workings of the communication pathways between tubular segments and the glomeruli
      and vasculature, with novel therapeutic agents in development. Particular
      progress has also been made in the visualization of tubuloglomerular feedback.
      SUMMARY: The review summarizes our current understanding of pathway functions in
      health and disease, as well as future therapeutic options to protect the healthy
      and injured kidney.

PMID- 27023840
TI  - Clearance of cardiovascular medications during hemodialysis.
AB  - PURPOSE OF REVIEW: To review the current understanding of hemodialysis-mediated
      clearance of commonly used cardiovascular medications. RECENT FINDINGS: Although
      cardiovascular drug dialyzability is poorly understood, many drug classes appear
      to include agents with substantially different degrees of dialyzability. Recent
      data suggest that more readily dialyzable beta-blockers associate with higher
      short-term mortality in patients initiating these drugs when on hemodialysis.
      Although this relationship was not observed in a later study with angiotensin
      converting enzyme inhibitors of varying dialyzability, studies of this kind are
      currently limited by pharmacokinetic data that are either incomplete or no longer
      applicable to modern hemodialysis procedures. SUMMARY: There are substantial
      deficits in our understanding of cardiovascular medication dialyzability, which
      relates in large part to advances in the process of hemodialysis that have
      rendered older studies of dialyzability irrelevant. The importance of
      cardiovascular disease in patients receiving hemodialysis demands a better
      understanding of the effect hemodialysis exerts on cardiovascular drug
      pharmacokinetics.

PMID- 27023841
TI  - Adherence to guidelines strongly improves reproducibility of brachial artery flow
      mediated dilation.
AB  - BACKGROUND: Brachial artery FMD is widely used as a non-invasive measure of
      endothelial function. Adherence to expert guidelines is believed to be of vital
      importance to obtain reproducible measurements. We conducted a systematic review
      of studies reporting on the reproducibility of the FMD in order to determine the
      relation between adherence to current expert guidelines for FMD measurement and
      its reproducibility. METHODS: Medline-database was searched through July 2015 and
      458 records were screened for FMD reproducibility studies reporting the mean
      difference and variance of repeated FMD measurements. An adherence score was
      assigned to each of the included studies based on reported adherence to published
      guidelines on the assessment of brachial artery FMD. A Typical Error Estimate
      (TEE) of the FMD was calculated for each included study. The relation between the
      FMD TEE and the adherence score was investigated by means of Pearson correlation
      coefficients and multiple linear regression analysis. RESULTS: Twenty-seven
      studies involving 48 study groups and 1537 subjects were included in the
      analyses. The adherence score ranged from 2.4 to 9.2 (out of a maximum of 10) and
      was strongly and inversely correlated with FMD TEE (adjusted R(2) = 0.36, P <
      0.01). Use of automated edge-detection software, continuous diameter measurement,
      true peak diameter for %FMD calculation, a stereostatic probe holder, and higher
      age emerged as factors associated with a lower FMD TEE. CONCLUSIONS: These data
      demonstrate that adherence to current expert consensus guidelines and applying
      contemporary techniques for measuring brachial artery FMD decreases its
      measurement error.

PMID- 27023842
TI  - [Actual medical care situation and therapeutic needs in multiple sclerosis:
      Impact of the Pharmaceutical Market Restructuring Act (AMNOG)].
AB  - BACKGROUND: The treatment of patients with multiple sclerosis (MS) is associated
      with constantly rising costs for the healthcare system and pharmaceuticals
      constitute 60 % of the direct medical costs. The Pharmaceutical Market
      Restructuring Act (Arzneimittelmarkt-Neuordnungsgesetz, AMNOG) came into force on
      1 January 2011 with the aim of limiting the costs of pharmaceuticals by
      obligating newly approved products to be subjected to an early evaluation of the
      additional benefits by the Federal Joint Committee (FJC, Gemeinsamer
      Bundesausschuss, G-BA). The majority of products evaluated up to October 2015 in
      neurology (5 out of 8) were approved for treatment of MS. OBJECTIVE: Has the
      AMNOG been able to fulfill the original aims? MATERIAL AND METHODS: Analysis of
      available information on MS therapies evaluated by the FJC between December 2010
      and October 2015. RESULTS: For various reasons an additional benefit could be
      shown in only 2 out of 5 assessment procedures for MS drugs. It is obvious that
      some methodological shortcomings of the process have to be improved. Additionally
      requirements for pivotal clinical trials have to be harmonized with AMNOG
      requirements taking the best available evidence and real-life data into
      consideration (e.g. non-interventional studies) and a closer collaboration
      between the FJC, healthcare providers and the neurological societies is
      necessary. CONCLUSION: The AMNOG procedure currently only partially fulfills the
      original aims, which could be the reason why guidelines play a more important
      role for therapy decision-making than FJC decisions. As the early evaluation
      procedure is an adaptive process methodological shortcomings might be overcome in
      the future; however, this requires a much closer collaboration between the FJC
      and neurological societies.

PMID- 27023843
TI  - [Intercultural adaptation of the AIMS in German language: A scale for abnormal
      involuntary movements].
AB  - BACKGROUND: Dyskinesias are abnormal involuntary movements and occur across many
      movement disorders. In Parkinson's disease dyskinesias can be troublesome and are
      a determinant of the quality of life throughout the course of the disease.
      Assessment and rating of dyskinesias is thus important for clinical assessment of
      patients, as well as for academic studies and clinical trials. The abnormal
      involuntary movement scale (AIMS) is an English language standardised, reliable
      and validated scale to evaluate dyskinesias. In this article we present a
      linguistically validated German version of AIMS. METHODS: The intercultural
      adaptation of the German translation was performed following an internationally
      accepted procedure. Firstly, two neurologists independently translated the
      original into German. Taking both versions into account, a consensus version was
      agreed on by both translators and was tested on 10 patients. This preliminary
      German version was then independently translated back into the original language
      by two different neurologists, and again, a consensus version was agreed on. All
      translators then compared this English version to the original. Subsequently, the
      German version was linguistically modified until it resulted in a final German
      version, which was agreed on by all translators, deemed linguistically
      acceptable, and the translation back into English was considered to be as
      unambiguous as possible. This final German version of AIMS was applied to 50
      patients in two different hospitals for diagnostic purposes and tested for
      feasibility and comprehension. RESULTS: In this paper, we present an
      intercultural adaptation of a linguistically validated German version of AIMS.

PMID- 27023844
TI  - Transcription as a Threat to Genome Integrity.
AB  - Genomes undergo different types of sporadic alterations, including DNA damage,
      point mutations, and genome rearrangements, that constitute the basis for
      evolution. However, these changes may occur at high levels as a result of cell
      pathology and trigger genome instability, a hallmark of cancer and a number of
      genetic diseases. In the last two decades, evidence has accumulated that
      transcription constitutes an important natural source of DNA metabolic errors
      that can compromise the integrity of the genome. Transcription can create the
      conditions for high levels of mutations and recombination by its ability to open
      the DNA structure and remodel chromatin, making it more accessible to DNA
      insulting agents, and by its ability to become a barrier to DNA replication. Here
      we review the molecular basis of such events from a mechanistic perspective with
      particular emphasis on the role of transcription as a genome instability
      determinant. 

PMID- 27023845
TI  - Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and
      Intracellular Signal Transduction.
AB  - Epidermal growth factor (EGF) and insulin receptor tyrosine kinases (RTKs)
      exemplify how receptor location is coupled to signal transduction. Extracellular
      binding of ligands to these RTKs triggers their concentration into vesicles that
      bud off from the cell surface to generate intracellular signaling endosomes. On
      the exposed cytosolic surface of these endosomes, RTK autophosphorylation selects
      the downstream signaling proteins and lipids to effect growth factor and
      polypeptide hormone action. This selection is followed by the recruitment of
      protein tyrosine phosphatases that inactivate the RTKs and deliver them by
      membrane fusion and fission to late endosomes. Coincidentally, proteinases inside
      the endosome cleave the EGF and insulin ligands. Subsequent inward budding of the
      endosomal membrane generates multivesicular endosomes. Fusion with lysosomes then
      results in RTK degradation and downregulation. Through the spatial positioning of
      RTKs in target cells for EGF and insulin action, the temporal extent of
      signaling, attenuation, and downregulation is regulated. 

PMID- 27023846
TI  - Structure and Function of the Mitochondrial Ribosome.
AB  - Mitochondrial ribosomes (mitoribosomes) perform protein synthesis inside
      mitochondria, the organelles responsible for energy conversion and adenosine
      triphosphate production in eukaryotic cells. Throughout evolution, mitoribosomes
      have become functionally specialized for synthesizing mitochondrial membrane
      proteins, and this has been accompanied by large changes to their structure and
      composition. We review recent high-resolution structural data that have provided
      unprecedented insight into the structure and function of mitoribosomes in mammals
      and fungi. 

PMID- 27023847
TI  - Maintenance and Expression of Mammalian Mitochondrial DNA.
AB  - Mammalian mitochondrial DNA (mtDNA) encodes 13 proteins that are essential for
      the function of the oxidative phosphorylation system, which is composed of four
      respiratory-chain complexes and adenosine triphosphate (ATP) synthase.
      Remarkably, the maintenance and expression of mtDNA depend on the mitochondrial
      import of hundreds of nuclear-encoded proteins that control genome maintenance,
      replication, transcription, RNA maturation, and mitochondrial translation. The
      importance of this complex regulatory system is underscored by the identification
      of numerous mutations of nuclear genes that impair mtDNA maintenance and
      expression at different levels, causing human mitochondrial diseases with
      pleiotropic clinical manifestations. The basic scientific understanding of the
      mechanisms controlling mtDNA function has progressed considerably during the past
      few years, thanks to advances in biochemistry, genetics, and structural biology.
      The challenges for the future will be to understand how mtDNA maintenance and
      expression are regulated and to what extent direct intramitochondrial cross talk
      between different processes, such as transcription and translation, is important.

PMID- 27023848
TI  - Shared Molecular Mechanisms of Membrane Transporters.
AB  - The determination of the crystal structures of small-molecule transporters has
      shed light on the conformational changes that take place during structural
      isomerization from outward- to inward-facing states. Rather than using a simple
      rocking movement of two bundles around a central substrate-binding site, it has
      become clear that even the most simplistic transporters utilize rearrangements of
      nonrigid bodies. In the most dramatic cases, one bundle is fixed while the other,
      structurally divergent, bundle carries the substrate some 18 A across the
      membrane, which in this review is termed an elevator alternating-access
      mechanism. Here, we compare and contrast rocker-switch, rocking-bundle, and
      elevator alternating-access mechanisms to highlight shared features and novel
      refinements to the basic alternating-access model. 

PMID- 27023850
TI  - Using low-contrast negative-tone PMMA at cryogenic temperatures for 3D electron
      beam lithography.
AB  - We report on a 3D electron beam lithography (EBL) technique using polymethyl
      methacrylate (PMMA) in the negative-tone regime as a resist. First, we briefly
      demonstrate 3D EBL at room temperature. Then we concentrate on cryogenic
      temperatures where PMMA exhibits a low contrast, which allows for straightforward
      patterning of 3D nano- and microstructures. However, conventional EBL patterning
      at cryogenic temperatures is found to cause severe damage to the microstructures.
      Through an extensive study of lithography parameters, exposure techniques, and
      processing steps we deduce a hypothesis for the cryogenic PMMA's structural
      evolution under electron beam irradiation that explains the damage. In accordance
      with this hypothesis, a two step lithography technique involving a wide-area pre
      exposure dose slightly smaller than the onset dose is applied. It enables us to
      demonstrate a >95% process yield for the low-temperature fabrication of 3D
      microstructures. 

PMID- 27023849
TI  - Mechanisms of Bacterial Transcription Termination: All Good Things Must End.
AB  - Transcript termination is essential for accurate gene expression and the removal
      of RNA polymerase (RNAP) at the ends of transcription units. In bacteria, two
      mechanisms are responsible for proper transcript termination: intrinsic
      termination and Rho-dependent termination. Intrinsic termination is mediated by
      signals directly encoded within the DNA template and nascent RNA, whereas Rho
      dependent termination relies upon the adenosine triphosphate-dependent RNA
      translocase Rho, which binds nascent RNA and dissociates the elongation complex.
      Although significant progress has been made in understanding these pathways,
      fundamental details remain undetermined. Among those that remain unresolved are
      the existence of an inactivated intermediate in the intrinsic termination
      pathway, the role of Rho-RNAP interactions in Rho-dependent termination, and the
      mechanisms by which accessory factors and nucleoid-associated proteins affect
      termination. We describe current knowledge, discuss key outstanding questions,
      and highlight the importance of defining the structural rearrangements of RNAP
      that are involved in the two mechanisms of transcript termination. 

PMID- 27023851
TI  - Green synthesis of silver nanoparticles using Rheum palmatum root extract and
      their antibacterial activity against Staphylococcus aureus and Pseudomonas
      aeruginosa.
AB  - In the present study, silver nanoparticles (AgNPs) were synthesized by using
      aqueous root extracts of Rheum palmatum and characterized by various
      spectroscopic methods. The nanoparticles were found to be in hexagonal and
      spherical shapes. The average particle size was found to be 121 +/- 2 nm with
      zeta potential values of -21.6 mv by dynamic light scattering (DLS) method. Gas
      chromatography-mass spectrometry (GC-MS) analysis of R. palmatum revealed 35
      compounds. The synthesized AgNPs showed significant activity against
      Staphylococcus aureus and Pseudomonas aeruginosa with IC90 values of 15 MUg/ml
      and IC50 values of 7.5 MUg/ml, respectively. The protein leakage level was high
      and morphological changes occurred in bacteria treated with AgNPs.

PMID- 27023852
TI  - A Novel Scatter Correction Method for Cone-Beam Computed Tomography.
AB  - In this article, a novel scatter correction approach was proposed based on the
      Klein-Nishina formulation. Through a series of deductions from this formulation,
      a principle was proposed that the photon intensity distribution was determined by
      the attenuation coefficient MU and the path length l. This means if 2 pencil
      beams pass through 2 objects with the same MUl, even if the attenuation
      coefficient MU and the path length l of the objects are different, they will
      still achieve the same photon intensity distribution, that is, the same point
      spread function. Subsequently, a novel scatter correction approach was
      established after a series of deductions based on this principle. The simulations
      and experiments demonstrated the correctness of our principle and the comparable
      correction effect of our scatter correction approach compared with the beam stop
      array method. Furthermore, because of the character of our method, the program
      has very high parallel computing features, which can dramatically increase the
      computation speed. 

PMID- 27023853
TI  - Inferior Vena Cava Filter Elucidation: How to Identify Specific Inferior Vena
      Cava Filter Types on Multi-Detector-Row Computed Tomography Imaging.
AB  - The use of inferior vena cava (IVC) filters in the United States has increased
      substantially over the last 3 decades. In addition, the number of Food and Drug
      Administration-approved devices has also increased during this time, and there
      are now more than 24 different IVC filter types that may be encountered in
      clinical practice. These devices vary substantially with regard to design,
      retrievability, and risk of potential complications that include fracture,
      penetration, embolization, migration, recurrent venous thromboembolism, and
      chronic IVC occlusion. A myriad of devices are now routinely encountered on multi
      detector-row computed tomography imaging, but it can be challenging to properly
      identify a specific IVC filter type. Proper device identification has important
      clinical consequences because each filter type has associated risks that may
      otherwise be overlooked. Identifying the specific filter type may allow further
      radiographic surveillance for known device-specific complications and may
      identify patients who can benefit from further medical treatment or prompt filter
      retrieval. Therefore, our purpose was to present a practical method to identify
      the various IVC filter types that may be encountered on multi-detector-row
      computed tomography imaging. 

PMID- 27023854
TI  - A New Method for Cone-Beam Computed Tomography Geometric Parameters Estimation.
AB  - This work demonstrates a new approach for geometric parameters estimation of cone
      beam computed tomography system from the coordinates of the centroids of 2
      projected point sources sampled over 360 degrees. Nonlinear object expression was
      derived for the coordinates of the centroids in terms of the geometric parameters
      after a slice of reasonable simplification, which aims to improve the convergence
      and robustness of the nonlinear object expression. All of the geometric
      parameters could be precisely estimated from the nonlinear object expression
      using the annealing algorithm. The simulations and experiments indicate more
      excellent convergence, robustness, and precision of our approach compared with
      other methods. Furthermore, our approach is insensitive to the initial value;
      namely, we do not need to set the value close to the true value to guarantee the
      convergence of the approach. 

PMID- 27023855
TI  - Advanced Imaging of the Scapula: What Every Radiologist Needs to Know.
AB  - The scapula plays a central role in shoulder motion and stability. A wide variety
      of anatomic variants as well as traumatic, neoplastic, and infectious pathologies
      can involve the scapula. Detection of scapular lesions using radiography can be
      challenging because of the obscuration by the overlying structures or incomplete
      imaging during shoulder magnetic resonance imaging or computed tomography
      examinations. Familiarity with imaging characteristics of these abnormalities
      will allow radiologists to better diagnose and characterize scapular disorders. 

PMID- 27023856
TI  - Diffusion-Weighted Magnetic Resonance Imaging in Distinguishing Between Mucin
      Producing and Serous Pancreatic Cysts.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility and
      reproducibility of diffusion-weighted imaging in distinguishing between mucin
      producing and serous pancreatic cysts. METHODS: Forty-four pancreatic cysts (43
      patients, 27 women; mean age, 57 years; 26 mucin-producing cysts, 18 serous
      cysts) that underwent histological examination or cyst analysis after diffusion
      weighted magnetic resonance imaging were retrospectively reviewed. Three blinded
      readers independently evaluated signal intensity and apparent diffusion
      coefficient (ADC). Intraobserver and interobserver agreements were calculated.
      Fisher exact test and Welch t test were used to compare signal intensity and ADC
      values, respectively, with pathological results. Receiver operating
      characteristic analysis was used to determine diagnostic accuracy of various
      thresholds for ADC. A P value less than 0.05 was considered statistically
      significant. RESULTS: Mean ADC values of the mucin-producing cysts were 3.26 *
      10, 3.27 * 10, and 3.35 * 10 mm/s for the 3 readers, respectively. Mean ADC
      values of the serous cysts were 2.86 * 10, 2.85 * 10, and 2.85 * 10 mm/s for the
      3 readers, respectively. Differences in ADC values between the 2 cyst groups were
      12.4%, 12.9%, and 14.8% for the 3 readers, respectively (P < 0.001).
      Intraobserver and interobserver agreement was excellent. A threshold ADC of 3 *
      10 mm/s resulted in correct identification of cysts in 77% to 81% of cases, with
      sensitivity and specificity ranging between 84% and 88% and 66% and 72%,
      respectively. CONCLUSIONS: Diffusion-weighted imaging may be a helpful tool in
      distinguishing between mucin-producing and serous pancreatic cysts.

PMID- 27023857
TI  - Radiation-Induced Liver Injury Mimicking Metastatic Disease in a Patient With
      Esophageal Cancer: Correlation of Positron Emission Tomography/Computed
      Tomography With Magnetic Resonance Imaging and Literature Review.
AB  - Post-radiation therapy evaluation of distal esophageal cancers with positron
      emission tomography/computed tomography can be problematic. Differentiation of
      recurrent neoplasm from postradiation changes is difficult in areas of
      fluorodeoxyglucose avidity in adjacent, incidentally irradiated organs. Few
      studies have described the magnetic resonance imaging appearance of radiation
      induced hepatic injury. We report a case of focal radiation-induced liver injury
      with a new focus of fluorodeoxyglucose uptake on posttreatment positron emission
      tomography as well as masslike enhancement and signal abnormality on magnetic
      resonance imaging, thus mimicking new liver metastasis. Correlation with
      radiation planning images suggested the correct diagnosis, which was confirmed on
      follow-up imaging. 

PMID- 27023858
TI  - Limitation of Virtual Noncontrasted Images in Evaluation of a Liver Lesion Status
      Post Transarterial Chemoembolization.
AB  - The authors describe a case of a patient with a solitary hepatocellular carcinoma
      status post transarterial chemoembolization. Follow-up imaging was performed
      using dual-energy computed tomography. The study was performed with and without
      contrast and a virtual noncontrast data set was constructed from the postcontrast
      images. The evaluation of this patient status post transarterial
      chemoembolization with virtual noncontrast alone erroneously suggested
      enhancement and viable tumor. However, examination of true noncontrast images
      revealed these findings to be due to the subtraction of iodine in Ethiodol within
      the treated lesion. 

PMID- 27023859
TI  - High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of
      Eye Movements in Mice.
AB  - BACKGROUND: The mouse is the most commonly used animal model in biomedical
      research because of recent advances in molecular genetic techniques. Studies
      related to eye movement in mice are common in fields such as ophthalmology
      relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR),
      neurology relating to the cerebellum's role in movement, and psychology relating
      to attention. Recording eye movements in mice, however, is technically difficult.
      METHODS: We developed a new algorithm for analyzing the three-dimensional (3D)
      rotation vector of eye movement in mice using high-speed video-oculography (VOG).
      The algorithm made it possible to analyze the gain and phase of VOR using the
      eye's angular velocity around the axis of eye rotation. RESULTS: When mice were
      rotated at 0.5 Hz and 2.5 Hz around the earth's vertical axis with their heads in
      a 30 degrees  nose-down position, the vertical components of their left eye
      movements were in phase with the horizontal components. The VOR gain was 0.42 at
      0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the
      turntable was 16.1 degrees  at 0.5 Hz and 4.88 degrees  at 2.5 Hz. CONCLUSIONS:
      To the best of our knowledge, this is the first report of this algorithm being
      used to calculate a 3D rotation vector of eye movement in mice using high-speed
      VOG. We developed a technique for analyzing the 3D rotation vector of eye
      movements in mice with a high-speed infrared CCD camera. We concluded that the
      technique is suitable for analyzing eye movements in mice. We also include a C++
      source code that can calculate the 3D rotation vectors of the eye position from
      two-dimensional coordinates of the pupil and the iris freckle in the image to
      this article.

PMID- 27023860
TI  - Acupuncture in Menopause (AIM) study: a pragmatic, randomized controlled trial.
AB  - OBJECTIVE: The aim of the study was to evaluate the short and long-term effects
      of acupuncture on vasomotor symptoms (VMS) and quality of life-related measures.
      METHODS: A total of 209 perimenopausal and postmenopausal women aged 45 to 60
      years, experiencing four or more VMS per day, were recruited from the community
      and randomized to receive up to 20 acupuncture treatments within the first 6
      months (acupuncture group) or the second 6 months (waitlist control group) of the
      12-month study period. The primary outcome was mean daily frequency of VMS.
      Secondary outcomes were VMS interference with daily life, sleep quality,
      depressive symptoms, somatic and other symptoms, anxiety, and quality of life.
      RESULTS: The VMS frequency declined by 36.7% at 6 months in the acupuncture group
      and increased by 6.0% in the control group (P < 0.001 for between-group
      comparison). At 12 months, the reduction from baseline in the acupuncture group
      was 29.4% (P < 0.001 for within-group comparison from baseline to 12 months),
      suggesting that the reduction was largely maintained after treatment.
      Statistically significant clinical improvement was observed after three
      acupuncture treatments, and maximal clinical effects occurred after a median of
      eight treatments. Persistent improvements were seen in many quality of life
      related outcomes in the acupuncture group relative to the control group.
      CONCLUSIONS: We found that a course of acupuncture treatments was associated with
      significant reduction in VMS, and several quality-of-life measures, compared with
      no acupuncture, and that clinical benefit persisted for at least 6 months beyond
      the end of treatment.

PMID- 27023861
TI  - Inflammatory/hemostatic biomarkers and coronary artery calcification in midlife
      women of African-American and White race/ethnicity: the Study of Women's Health
      Across the Nation (SWAN) heart study.
AB  - OBJECTIVE: Inflammatory/hemostatic biomarkers are associated with coronary heart
      disease events, but relationships in asymptomatic midlife women are uncertain. We
      evaluated separately whether high-sensitivity C-reactive protein (hsCRP),
      fibrinogen, plasminogen-activator inhibitor 1, tissue plasminogen activator
      antigen, and circulating factor VII (factor VIIc) were associated with coronary
      artery calcification (CAC) in healthy midlife women. METHODS: A cross-sectional
      study was performed of participants from the Study of Women's Health Across the
      Nation. Logistic and Tobit regression was used to assess associations between log
      transformed biomarkers, and CAC presence (CAC > 0) and extent. Effect
      modification by race/ethnicity was evaluated. RESULTS: The study included 372
      women (mean age 51.3 y; 35.2% African-American). All biomarkers were positively
      associated with CAC presence and extent (P < 0.001 for all), adjusting for
      Framingham risk score, site, race/ethnicity, menopause status, income, and
      education. Additional adjustment for body mass index explained all associations
      except for factor VIIc, which remained associated with CAC extent only (P =
      0.02). Final adjustment for insulin resistance, family history of cardiovascular
      disease, and cardiovascular medication use produced similar results. Associations
      between hsCRP, and CAC presence and extent were modified by race/ethnicity (P <
      0.05). Log(hsCRP) was positively associated with CAC presence (odds ratio 3.25;
      95% CI, 1.53-6.90; P = 0.002; per 1 log unit increase) and CAC extent (beta =
      19.66; SE = 7.67; P = 0.01; per 1 log unit increase) in African-Americans only.
      CONCLUSIONS: Inflammatory/hemostatic biomarkers were associated with CAC through
      obesity, except for factor VIIc. Among African-American women only, hsCRP was
      independently associated with CAC, suggesting that hsCRP may have a role in
      coronary heart disease prevention in African-American midlife women.

PMID- 27023862
TI  - Risk of venous thromboembolism associated with local and systemic use of hormone
      therapy in peri- and postmenopausal women and in relation to type and route of
      administration.
AB  - OBJECTIVE: The aim of the study was to assess the risk of venous thromboembolism
      (VTE) associated with systemic hormone therapy according to type and to route of
      administration and the risk of VTE associated with locally administered estrogen.
      METHODS: In this case-control study, conducted in Sweden between 2003 and 2009,
      we included 838 cases of VTE and 891 controls with a mean age of 55 years.
      Controls were matched by age to the cases and randomly selected from the
      population. We used logistic regression to calculate odds ratios (ORs) with 95%
      CIs and adjusted for smoking, body mass index, and immobilization. RESULTS:
      Current use of any hormone therapy was associated with an increased risk of VTE
      (OR 1.72, 95% CI 1.34-2.20). For estrogen in combination with progestogen the OR
      was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78
      2.21). In orally administered estrogen combined with progestogen, the OR was
      slightly, but not significantly, higher among users of medroxyprogesterone
      acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR
      2.55, 95% CI 1.50-3.40). Transdermal estrogen combined with progestogen was not
      associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16). For
      local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI
      0.43-1.10). CONCLUSIONS: The risk of VTE risk is higher in users of systemic
      combined estrogen-progestogen treatment than in users of estrogen only.
      Furthermore, the risk of VTE was lower for women who used local estrogen than
      among those using oral estrogen only. Transdermal estrogen only treatment and
      estrogen for local effect seem not to be related to an increased risk of VTE.

PMID- 27023863
TI  - Intimate partner violence and the climacteric.

PMID- 27023864
TI  - Flexible parametric survival models built on age-specific antimullerian hormone
      percentiles are better predictors of menopause.
AB  - OBJECTIVE: This study aimed to improve existing prediction models for age at
      menopause. METHODS: We identified all reproductive aged women with regular
      menstrual cycles who met our eligibility criteria (n = 1,015) in the Tehran Lipid
      and Glucose Study-an ongoing population-based cohort study initiated in 1998.
      Participants were examined every 3 years and their reproductive histories were
      recorded. Blood levels of antimullerian hormone (AMH) were measured at the time
      of recruitment. Age at menopause was estimated based on serum concentrations of
      AMH using flexible parametric survival models. The optimum model was selected
      according to Akaike Information Criteria and the realness of the range of
      predicted median menopause age. RESULTS: We followed study participants for a
      median of 9.8 years during which 277 women reached menopause and found that a
      spline-based proportional odds model including age-specific AMH percentiles as
      the covariate performed well in terms of statistical criteria and provided the
      most clinically relevant and realistic predictions. The range of predicted median
      age at menopause for this model was 47.1 to 55.9 years. For those who reached
      menopause, the median of the absolute mean difference between actual and
      predicted age at menopause was 1.9 years (interquartile range 2.9). CONCLUSIONS:
      The model including the age-specific AMH percentiles as the covariate and using
      proportional odds as its covariate metrics meets all the statistical criteria for
      the best model and provides the most clinically relevant and realistic
      predictions for age at menopause for reproductive-aged women.

PMID- 27023867
TI  - Enhanced flat adenoma detection rate with high definition colonoscopy plus i-scan
      for average-risk colorectal cancer screening.
AB  - BACKGROUND AND AIM: The usefulness of high definition colonoscopy plus i-scan
      (HD+i-SCAN) for average-risk colorectal cancer screening has not been fully
      assessed. The detection rate of adenomas and other measurements such as the
      number of adenomas per colonoscopy and the flat adenoma detection rate have been
      recognized as markers of colonoscopy quality. The aim of the present study was to
      compare the diagnostic performance of an HD+i-SCAN with that of standard
      resolution white-light colonoscope. METHODS: This is a retrospective analysis of
      a prospectively collected screening colonoscopy database. A comparative analysis
      of the diagnostic yield of an HD+i-SCAN or standard resolution colonoscopy for
      average-risk colorectal screening was conducted. RESULTS: During the period of
      study, 155/163 (95.1%) patients met the inclusion criteria. The mean age was 56.9
      years. Sixty of 155 (39%) colonoscopies were performed using a HD+i-SCAN. Adenoma
      detection-rates during the withdrawal of the standard resolution versus HD+i-SCAN
      colonoscopies were 29.5% and 30% (p = n.s.). Adenoma/colonoscopy values for
      standard resolution versus HD+i-SCAN colonoscopies were 0.46 (SD = 0.9) and 0.72
      (SD = 1.3) (p = n.s.). A greater number of flat adenomas were detected in the
      HD+i-SCAN group (6/60 versus 2/95) (p < .05). Likewise, serrated adenomas/polyps
      per colonoscopy were also higher in the HD+i-SCAN group. CONCLUSIONS: A HD+i-SCAN
      colonoscopy increases the flat adenoma detection rate and serrated
      adenomas/polyps per colonoscopy compared to a standard colonoscopy in average
      risk screening population. HD+i-SCAN is a simple, available procedure that can be
      helpful, even for experienced providers. The performance of HD+i-SCAN and
      substantial prevalence of flat lesions in our average-risk screening cohort
      support its usefulness in improving the efficacy of screening colonoscopies.

PMID- 27023866
TI  - Adiponectin at Physiologically Relevant Concentrations Enhances the
      Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling.
AB  - Clinical studies have identified hypoadiponectinemia as an independent
      hypertension risk factor. It is known that adiponectin (APN) can directly cause
      vasodilation, but the doses required exceed physiologic levels several fold. In
      the current study, we determine the effect of physiologically relevant APN
      concentrations upon vascular tone, and investigate the mechanism(s) responsible.
      Physiologic APN concentrations alone induced no significant vasorelaxation.
      Interestingly, pretreatment of wild type mouse aortae with physiologic APN levels
      significantly enhanced acetylcholine (ACh)-induced vasorelaxation (P<0.01), an
      endothelium-dependent and nitric oxide (NO)-mediated process. Knockout of
      adiponectin receptor 1 (AdipoR1) or caveolin-1 (Cav-1, a cell signaling
      facilitating molecule), but not adiponectin receptor 2 (AdipoR2) abolished APN
      enhanced ACh-induced vasorelaxation. Immunoblot assay revealed APN promoted the
      AdipoR1/Cav1 signaling complex in human endothelial cells. Treatment of HUVECs
      with physiologic APN concentrations caused significant eNOS phosphorylation and
      nitric oxide (NO) production (P<0.01), an effect abolished in knockdown of either
      AdipoR1 or Cav-1. Taken together, these data demonstrate for the first time
      physiologic APN levels enhance the vasorelaxative response to ACh by inducing NO
      production through AdipoR1/Cav-1 mediated signaling. In physiologic conditions,
      APN plays an important function of maintaining vascular tone. 

PMID- 27023865
TI  - Electrophysiology and metabolism of caveolin-3-overexpressing mice.
AB  - Caveolin-3 (Cav-3) plays a critical role in organizing signaling molecules and
      ion channels involved in cardiac conduction and metabolism. Mutations in Cav-3
      are implicated in cardiac conduction abnormalities and myopathies. Additionally,
      cardiac-specific overexpression of Cav-3 (Cav-3 OE) is protective against
      ischemic and hypertensive injury, suggesting a potential role for Cav-3 in basal
      cardiac electrophysiology and metabolism involved in stress adaptation. We
      hypothesized that overexpression of Cav-3 may alter baseline cardiac conduction
      and metabolism. We examined: (1) ECG telemetry recordings at baseline and during
      pharmacological interventions, (2) ion channels involved in cardiac conduction
      with immunoblotting and computational modeling, and (3) baseline metabolism in
      Cav-3 OE and transgene-negative littermate control mice. Cav-3 OE mice had
      decreased heart rates, prolonged PR intervals, and shortened QTc intervals with
      no difference in activity compared to control mice. Dobutamine or propranolol did
      not cause significant changes between experimental groups in maximal (dobutamine)
      or minimal (propranolol) heart rate. Cav-3 OE mice had an overall lower
      chronotropic response to atropine. The expression of Kv1.4 and Kv4.3 channels,
      Nav1.5 channels, and connexin 43 were increased in Cav-3 OE mice. A computational
      model integrating the immunoblotting results indicated shortened action potential
      duration in Cav-3 OE mice linking the change in channel expression to the
      observed electrophysiology phenotype. Metabolic profiling showed no gross
      differences in VO2, VCO2, respiratory exchange ratio, heat generation, and
      feeding or drinking. In conclusion, Cav-3 OE mice have changes in ECG intervals,
      heart rates, and cardiac ion channel expression. These findings give novel
      mechanistic insights into previously reported Cav-3 dependent cardioprotection.

PMID- 27023869
TI  - Correction: Influence of Serotonin Transporter Gene Polymorphisms and Adverse
      Life Events on Depressive Symptoms in the Elderly: A Population-Based Study.

PMID- 27023868
TI  - Performance of the GeneXpert Ebola Assay for Diagnosis of Ebola Virus Disease in
      Sierra Leone: A Field Evaluation Study.
AB  - BACKGROUND: Throughout the Ebola virus disease (EVD) epidemic in West Africa,
      field laboratory testing for EVD has relied on complex, multi-step real-time
      reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR
      test would reduce time to results and potentially increase access to testing. We
      evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical
      venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field
      biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR
      ("Trombley assay"). METHODS AND FINDINGS: This study was conducted in the Public
      Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using
      residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens
      (n = 218) were collected from suspected or confirmed EVD patients between April 1
      and July 20, 2015. BS specimens (n = 71) were collected as part of a national
      postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS
      specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein
      [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens
      were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling
      methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In
      all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were
      reported as "invalid" or "error" and were excluded, leaving 211 WB and 64 BS
      samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive
      samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%-100%), and 181/189
      Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence
      interval (CI) 91.8%-98.2%). Seven of the eight Trombley-negative, Xpert-positive
      (Xpert cycle threshold [Ct] range 37.7-43.4) WB samples were confirmed to be
      follow-up submissions from previously Trombley-positive EVD patients, suggesting
      a revised Xpert specificity of 99.5% (95% CI 97.0%-100%). For Xpert-positive WB
      samples (n = 22), Xpert NP Ct values were consistently lower than GP Ct values
      (mean difference -4.06, 95% limits of agreement -6.09, -2.03); Trombley (NP) Ct
      values closely matched Xpert NP Ct values (mean difference -0.04, 95% limits of
      agreement -2.93, 2.84). Xpert results (positive/negative) for WB sampled by
      pipette versus swab were concordant for 78/79 (98.7%) WB samples, with comparable
      Ct values for positive results. For BS specimens, 20/20 Trombley-positive samples
      were Xpert-positive (sensitivity 100%, 95% CI 83.2%-100%), and 44/44 Trombley
      negative samples were Xpert-negative (specificity 100%, 95% CI 92.0%-100%). This
      study was limited to testing residual diagnostic samples, some of which had been
      frozen before use; it was not possible to test the performance of the Xpert Ebola
      assay at point of care. CONCLUSIONS: The Xpert Ebola assay had excellent
      performance compared to an established RT-PCR benchmark on WB and BS samples in a
      field laboratory setting. Future studies should evaluate feasibility and
      performance outside of a biocontainment laboratory setting to facilitate expanded
      access to testing.

PMID- 27023870
TI  - Saphenous Vein Graft Disease and Serum Erythropoietin Level.

PMID- 27023875
TI  - Making Sense of Research: An Introduction for Health and Social Care
      Practitioners - Third edition Hek Gill , Moule Pam Making Sense of Research: An
      Introduction for Health and Social Care Practitioners - Third edition 155 Sage
      9781412923620 141292362X.
AB  - Updated to include literature search techniques, meta-analysis, data protection
      issues and critical appraisal tools, this pocket-size book is a 'straightforward
      guide to the basics'.

PMID- 27023871
TI  - Domestication Syndrome Is Investigated by Proteomic Analysis between Cultivated
      Cassava (Manihot esculenta Crantz) and Its Wild Relatives.
AB  - Cassava (Manihot esculenta Crantz) wild relatives remain a largely untapped
      potential for genetic improvement. However, the domestication syndrome phenomena
      from wild species to cultivated cassava remain poorly understood. The analysis of
      leaf anatomy and photosynthetic activity showed significantly different between
      cassava cultivars SC205, SC8 and wild relative M. esculenta ssp. Flabellifolia
      (W14). The dry matter, starch and amylose contents in the storage roots of
      cassava cultivars were significantly more than that in wild species. In order to
      further reveal the differences in photosynthesis and starch accumulation of
      cultivars and wild species, the globally differential proteins between cassava
      SC205, SC8 and W14 were analyzed using 2-DE in combination with MALDI-TOF tandem
      mass spectrometry. A total of 175 and 304 proteins in leaves and storage roots
      were identified, respectively. Of these, 122 and 127 common proteins in leaves
      and storage roots were detected in SC205, SC8 and W14, respectively. There were
      11, 2 and 2 unique proteins in leaves, as well as 58, 9 and 12 unique proteins in
      storage roots for W14, SC205 and SC8, respectively, indicating proteomic changes
      in leaves and storage roots between cultivated cassava and its wild relatives.
      These proteins and their differential regulation across plants of contrasting
      leaf morphology, leaf anatomy pattern and photosynthetic related parameters and
      starch content could contribute to the footprinting of cassava domestication
      syndrome. We conclude that these global protein data would be of great value to
      detect the key gene groups related to cassava selection in the domestication
      syndrome phenomena. 

PMID- 27023872
TI  - Brand Suicide? Memory and Liking of Negative Brand Names.
AB  - Negative brand names are surprisingly common in the marketplace (e.g., Poison
      perfume; Hell pizza, and Monster energy drink), yet their effects on consumer
      behavior are currently unknown. Three studies investigated the effects of
      negative brand name valence on brand name memory and liking of a branded product.
      Study 1 demonstrates that relative to non-negative brand names, negative brand
      names and their associated logos are better recognised. Studies 2 and 3
      demonstrate that negative valence of a brand name tends to have a detrimental
      influence on product evaluation with evaluations worsening as negative valence
      increases. However, evaluation is also dependent on brand name arousal, with high
      arousal brand names resulting in more positive evaluations, such that moderately
      negative brand names are equally as attractive as some non-negative brand names.
      Study 3 shows evidence for affective habituation, whereby the effects of negative
      valence reduce with repeated exposures to some classes of negative brand name. 

PMID- 27023876
TI  - How I do it: novel parastomal herniorrhaphy utilizing transversus abdominis
      release.
AB  - INTRODUCTION: Parastomal hernias are a complex surgical problem affecting a large
      number of patients. Recurrences continue to occur despite various methods of
      repair. We present a novel method of open parastomal hernia repair with
      retromuscular mesh reinforcement in a modified Sugarbaker configuration. METHODS:
      A full mildline laparotomy is performed and all adhesions are taken down. We then
      perform an open parastomal hernia repair by utilizing retromuscular dissection,
      posterior component separation via transversus abdominis release, and
      lateralization of the bowel utilizing a modified Sugarbaker mesh configuration
      within the retromuscular space. We demonstrate this technique in a cadaveric
      model for illustrative purposes. DISCUSSION: This repair provides the benefits of
      an open posterior component separation with transversus abdominis release and
      maintains the biomechanics of a functional abdominal wall, all while
      simultaneously benefitting from the advantages of mesh reinforcement in a
      modified Sugarbaker configuration. Our clinical experience with this novel
      technique to this point has been positive.

PMID- 27023878
TI  - Vegetables intake and venous thromboembolism: a systematic review.
AB  - A higher intake of vegetables has been convincingly associated with a decreased
      risk of arterial thrombotic disorders, so that a similar association may be
      expected with venous thromboembolism. An electronic search was conducted in
      Medline, Web of Science and Scopus to identify epidemiological studies that
      investigated the independent association between intake of vegetables and risk of
      venous thrombosis. Our systematic literature search allowed to identify four
      prospective and one case-control studies. Although a lower risk of venous
      thromboembolism was reported in one prospective and one case-control studies, no
      significant association was found between larger intake of vegetables and risk of
      venous thrombosis in the remaining three large prospective studies. Taken
      together, the epidemiological data available in the current scientific literature
      do not support the notion that higher consumption of vegetables may have a
      significant impact on the risk of venous thrombosis. 

PMID- 27023877
TI  - Long-term results and complications related to Crurasoft(r) mesh repair for
      paraesophageal hiatal hernias.
AB  - PURPOSE: The application of mesh-reinforced hiatal closure has resulted in a
      significant reduction in recurrence rates in comparison with primary suture
      repair. However, the use of meshes has not completely extended in all the cases
      of large paraesophageal hiatal hernias (LPHH) due to the complications related to
      them. The aim of this study is to present our long-term results and complications
      related to Crurasoft(r) mesh (Bard) for the treatment of LPHH. METHODS: From
      January 2004 to December 2014, 536 consecutive patients underwent open or
      laparoscopic fundoplication for gastroesophageal reflux disease or LPHH at Ramon
      y Cajal University Hospital. Primary simple suture of the crura and additional
      reinforcement with a Crurasoft(r) mesh (Bard) was performed in 93 patients (17.35
      %). Radiologic hiatal hernia recurrence and mesh-related complications were
      investigated. RESULTS: Of the 93 patients undergoing mesh repair, there were 28
      male and 65 female with a mean age of 67.27 years (range 22-87 years).
      Laparoscopic surgery was attended in 88.2 % of the cases, and open surgery in the
      rest 11.8 %. Mean operative time was 167.05 min (range 90-370 min). Median
      postoperative stay was 4.79 days (range 1-41 days). Conversion rate was 8.53 % (7
      patients). Intraoperative complications were described in 10.75 % (10 patients),
      but all of them, except in one case, could be managed laparoscopically. Overall
      postoperative complications rate was 28 %. Early postoperative complications
      occurred in 11 patients (12 %), respectively, for grades 2 (6 cases), 3b (1 case)
      and 5 (4 cases) according to the Clavien-Dindo classification. Late postoperative
      complications occurred in 15 patients (16 %), respectively, for grades 1 (7
      cases), 2 (2 cases), 3b (5 cases) and 5 (1 case) according to the Clavien-Dindo
      classification. Thirty day-mortality rate was 4.3 %. Mortality rate specific
      associated with the mesh was 1 %. Reoperation rate was 5.4 %. After a median
      follow-up of 76.33 months (range 3-130 months), 8 patients (9 %) developed a
      recurrent hiatal hernia. Mesh was removed in three cases (3.22 %). CONCLUSIONS:
      In our experience, the recurrence rate in patients with a Crurasoft(r) (Bard) is
      acceptable. However, the rate of postoperative complications and mortality is
      excessive. The use of meshes in the hiatus keeps on being controversial due to
      the severe complications related to them. It would be advisable to compare our
      results in the non-mesh group in terms of recurrences and complications, to
      determine if meshes in the hiatus should be given in these patients due to its
      high rate of complications.

PMID- 27023879
TI  - Genetic susceptibility to deep venous thromboembolism: the roles of inherited
      thrombophilia polymorphisms.
AB  - Recently much attention has been paid to the possibly considerable role of the
      thrombophilic gene polymorphisms in the pathogenesis of deep venous
      thromboembolism (DVT). However, the reported results are controversial. Hence,
      this study aimed to disclose the association between factor VII (FVII) 10976G/A,
      angiotensin-converting enzyme (ACE; intron 16 I/D), glycoprotein Ia (GPIa)
      807C/T, tissue-type plasminogen activator (t-PA; intron 8 D/I) and tissue-factor
      pathway inhibitor 536C/T polymorphisms and DVT. We investigated these gene
      polymorphisms in 693 study participants including 193 patients who showed
      clinical symptoms of DVT and 500 healthy individuals without both personal and
      family histories of thromboembolic disorders. Genotyping was performed using the
      amplification refractory mutation system-polymerase chain reaction (ARMS-PCR)
      technique. Comparison of genotypes distribution revealed that the FVII 10976G/A
      polymorphism was significantly related with DVT (P < 0.05), whereas there was no
      association between the ACE (intron 16 I/D), GPIa807C/T, t-PA (intron 8 D/I) and
      tissue-factor pathway inhibitor 536C/T gene polymorphisms and DVT (P > 0.05). In
      addition, the prevalence of homozygote genotype and mutant allele for FVII
      10976G/A polymorphism was significantly higher in cases compared with controls (P
      < 0.05). Taken together, our data provide evidence to support the hypothesis that
      FVII 10976G/A polymorphism may be associated with a predisposition to DVT. 

PMID- 27023880
TI  - Which components of the CHA2DS2-VASc score are the most important in obstructive
      sleep apnea patients with atrial fibrillation?
AB  - Elevated thromboembolic risk is observed in patients with atrial fibrillation.
      The arrhythmia often co-exists with other diseases like obstructive sleep apnea
      (OSA), which adds to the thrombogenic profile and makes the proper assessment of
      thromboembolic risk difficult. The aim of the study was to establish how the
      prevalence of thromboembolic risk factors differs in patients with and without
      OSA. CHA2DS2-VASc score was used to assess thromboembolic risk in continuous
      atrial fibrillation patients prequalified for atrial fibrillation ablation. All
      266 patients included in the study had a polygraphy examination. Patients were
      divided into a group with apnea-hypopnea index (AHI) <15/h, and those with AHI
      15/h or above, who were considered as having OSA. The study population was aged
      57.6 +/- 10.1 years, and 65.0% of the subjects were male. OSA was diagnosed in 47
      patients. In OSA patients, the following CHA2DS2-VASc risk factors had
      significantly higher prevalence: congestive heart failure (6.5 vs. 0.5%; P =
      0.02), arterial hypertension (93.5 vs. 70.9%; P = 0.01), diabetes mellitus (26.1
      vs. 6.8%; P = 0.003), and history of vascular disease (23.9 vs. 8.2%; P = 0.006)
      than in non-OSA patients. Nonsignificant differences were noticed in the history
      of stroke, age categories, or sex. After dividing patients into four groups, that
      is non-OSA, mild OSA, moderate OSA, and severe OSA the same risk factors as
      previously stated remained significant (P < 0.05). The strongest contributors,
      responsible for elevated thromboembolic risk observed in atrial fibrillation
      patients with OSA are congestive heart failure, arterial hypertension, diabetes
      mellitus, and vascular disease. Higher comorbidity burden is another argument for
      including OSA into the risk assessment schemes in atrial fibrillation patients. 

PMID- 27023881
TI  - Does fist pumping/clenching during venipuncture activate blood coagulation?

PMID- 27023882
TI  - Angiotensin receptor blocker improves a stress-induced prothrombotic state in a
      murine model.

PMID- 27023884
TI  - Optical Coherence Tomography Angiography of Retinal Vein Occlusion.
AB  - Retinal vein occlusion is the second most common cause of retinal vascular
      disease after diabetic retinopathy and is a frequent cause of significant vision
      loss and associated morbidity. Currently, fluorescein angiography is the gold
      standard for imaging of the retinal and choroidal vasculature. However, this
      imaging modality is invasive, involving the use of an intravenous contrast agent
      that can cause systemic side effects and rarely, anaphylaxis. Optical coherence
      tomography angiography is a noninvasive, depth-resolved imaging modality that
      allows for the appreciation of spatial relationships of fundus vessels and
      enables detailed en face visualization of the superficial and deep retinal
      vasculature separately without the risk of adverse affects associated with the
      intravenous administration of fluorescein dye. When viewed alongside
      corresponding structural B-scans, optical coherence tomography angiography
      demonstrates almost all of the clinical and fluorescein angiographic findings
      that are characteristic of acute and chronic retinal vein occlusion, such as a
      decrease in capillary perfusion, macular edema, vascular dilation, foveal
      avascular zone enlargement, and venous-venous collateral formation. 

PMID- 27023883
TI  - Immunobiotic Bifidobacteria Strains Modulate Rotavirus Immune Response in Porcine
      Intestinal Epitheliocytes via Pattern Recognition Receptor Signaling.
AB  - In this work, we aimed to characterize the antiviral response of an originally
      established porcine intestinal epithelial cell line (PIE cells) by evaluating the
      molecular innate immune response to rotavirus (RVs). In addition, we aimed to
      select immunomodulatory bacteria with antiviral capabilities. PIE cells were
      inoculated with RVs isolated from different host species and the infective titers
      and the molecular innate immune response were evaluated. In addition, the
      protection against RVs infection and the modulation of immune response by
      different lactic acid bacteria (LAB) strains was studied. The RVs strains OSU
      (porcine) and UK (bovine) effectively infected PIE cells. Our results also showed
      that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune
      responses with activation of IRF3 and NF-kappaB, induction of IFN-beta and up
      regulation of the interferon stimulated genes MxA and RNase L. Among the LAB
      strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly
      reduced RVs titers in infected PIE cells. The beneficial effects of both
      bifidobacteria were associated with reduction of A20 expression, and improvements
      of IRF-3 activation, IFN-beta production, and MxA and RNase L expressions. These
      results indicate the value of PIE cells for studying RVs molecular innate immune
      response in pigs and for the selection of beneficial bacteria with antiviral
      capabilities. 

PMID- 27023886
TI  - Underestimated Challenges Adopting the Conceptual Approach.

PMID- 27023885
TI  - Genome-Wide Association Study Singles Out SCD and LEPR as the Two Main Loci
      Influencing Intramuscular Fat Content and Fatty Acid Composition in Duroc Pigs.
AB  - Intramuscular fat (IMF) content and fatty acid composition affect the
      organoleptic quality and nutritional value of pork. A genome-wide association
      study was performed on 138 Duroc pigs genotyped with a 60k SNP chip to detect
      biologically relevant genomic variants influencing fat content and composition.
      Despite the limited sample size, the genome-wide association study was powerful
      enough to detect the association between fatty acid composition and a known
      haplotypic variant in SCD (SSC14) and to reveal an association of IMF and fatty
      acid composition in the LEPR region (SSC6). The association of LEPR was later
      validated with an independent set of 853 pigs using a candidate quantitative
      trait nucleotide. The SCD gene is responsible for the biosynthesis of oleic acid
      (C18:1) from stearic acid. This locus affected the stearic to oleic desaturation
      index (C18:1/C18:0), C18:1, and saturated (SFA) and monounsaturated (MUFA) fatty
      acids content. These effects were consistently detected in gluteus medius,
      longissimus dorsi, and subcutaneous fat. The association of LEPR with fatty acid
      composition was detected only in muscle and was, at least in part, a consequence
      of its effect on IMF content, with increased IMF resulting in more SFA, less
      polyunsaturated fatty acids (PUFA), and greater SFA/PUFA ratio. Marker
      substitution effects estimated with a subset of 65 animals were used to predict
      the genomic estimated breeding values of 70 animals born 7 years later. Although
      predictions with the whole SNP chip information were in relatively high
      correlation with observed SFA, MUFA, and C18:1/C18:0 (0.48-0.60), IMF content and
      composition were in general better predicted by using only SNPs at the SCD and
      LEPR loci, in which case the correlation between predicted and observed values
      was in the range of 0.36 to 0.54 for all traits. Results indicate that markers in
      the SCD and LEPR genes can be useful to select for optimum fatty acid profiles of
      pork. 

PMID- 27023887
TI  - Educator or Counselor? Navigating Uncertain Boundaries in the Clinical
      Environment.
AB  - BACKGROUND: Nurse educators in the clinical environment experience great rewards
      and challenges in their work with undergraduate students. However, closely
      working with students can lead to the challenge of intervening with those who are
      emotionally distressed. How do nurse educators navigate the precarious and subtle
      territory between educating and counseling? METHOD: This article briefly reviews
      how boundaries are explored in nursing. Two case studies are presented to
      demonstrate how nurse educators can determine when their support and education
      begins to move into the counseling role. Finally, future directions for nurse
      educators are suggested. RESULTS: Little research exists that examines how nurse
      educators navigate the boundaries between educator and counselor roles with
      students in clinical settings. CONCLUSION: Navigating between the educator and
      counselor roles with students experiencing emotional distress in clinical
      settings can be challenging for nurse educators.

PMID- 27023888
TI  - Evaluation of a Summer Bridge: Critical Component of the Leadership 2.0 Program.
AB  - BACKGROUND: Summer bridges facilitate the transition from high school to college.
      Although many schools employ summer bridges, few have published outcomes. This
      article's purpose is to share preconceptions of college by underrepresented and
      disadvantaged nursing students and describe important elements and long-term
      impact of a summer bridge, a component of the Leadership 2.0 program. METHOD: A
      longitudinal study design was used to collect baseline, short-term, and long-term
      post-summer bridge data. Methods included pre- and postsurveys, interviews, and
      focus groups. RESULTS: After bridge completion, students felt more prepared for
      the nursing program. Students ranked socialization components as most important.
      The summer bridge had lasting impact through the first year, where grade point
      average and retention of underrepresented and disadvantaged bridge students was
      comparable to the majority first-year students. CONCLUSION: The summer bridge was
      effective in preparing nursing students for the first year of college. Through
      holistic evaluation, unique aspects of socialization critical to student success
      were uncovered.

PMID- 27023889
TI  - Nursing Students' Perceptions of a Hearing Voices Simulation and Role-Play:
      Preparation for Mental Health Clinical Practice.
AB  - BACKGROUND: Baccalaureate nursing students experience anxiety before working with
      patients with mental illness who hear voices. A hearing voices simulation and
      role-play was proposed as an approach to preparing students for clinical
      practice. METHOD: A qualitative interpretive phenomenological method was used to
      determine students' perceptions of the simulation experience before their first
      mental health clinical rotation. RESULTS: Through the experience of the Walking
      in the Shoes of Patients activity, written student surveys revealed themes of
      Reflecting on Past Experiences, Developing Changed Perspectives, and Different
      Approaches to Care. CONCLUSION: The hearing voices simulation provided students
      with a greater understanding of the experience of hearing voices, and the role
      play helped students to gain personal insight into patients' behaviors and
      practice skills learned in preparation for their first mental health clinical
      experience.

PMID- 27023890
TI  - Teaching a Systems Approach: An Innovative Quality Improvement Project.
AB  - BACKGROUND: Nurse practitioners are required to navigate complex health care
      systems. Quality improvement (QI) projects provide the opportunity for nurse
      practitioner students to learn systems knowledge and improve health care outcomes
      in patient populations. A gap in the literature exists around how to
      systematically teach, apply, and measure QI curricular objectives at the master's
      level. METHOD: Six faculty evaluated the QI project for the psychiatric nurse
      practitioner master's program by identifying the most challenging QI concepts for
      students to apply, revising their teaching strategies to address gaps, and
      retrospectively evaluating the outcomes of these curriculum changes by comparing
      student outcomes before and after the curricular changes. RESULTS: A significant
      difference was noted on QI project performance between students in the 2014 and
      2015 graduating classes, measured by the scores earned on students' final papers
      (t[92] = 1.66, p = .05, d = .34, r(2) = .0289). CONCLUSION: Theoretical
      principles of adult and cooperative learning were used to inform curricular
      changes to enhance student's acquisition of QI skills.

PMID- 27023891
TI  - Incorporation of Sexual Violence in Nursing Curricula Using Trauma-Informed Care:
      A Case Study.
AB  - BACKGROUND: One in five women will experience sexual violence in their lifetime.
      As a consequence of this violence, survivors face health care concerns such as
      depression, anxiety, substance abuse, and gynecologic problems. Nurses are at the
      forefront of health care delivery to survivors of sexual violence, yet literature
      about nursing curricula addressing sexual violence is scant. METHOD: A holistic,
      single-case study from a student survivor about the impact of sexual violence,
      being taught from a trauma-informed care perspective, is presented. RESULTS: The
      powerful case study highlights the personal and professional benefits stemming
      from a sexual violence curriculum being taught from a trauma-informed care lens.
      The student survivor reports personal growth and an understanding of herself, as
      well as a new framework with which to care for patients who have experienced
      sexual violence. CONCLUSION: In preparation to deliver care to sexual violence
      survivors, students must be educated about the prevalence, long-term sequela, and
      health care needs of survivors, which can be effectively done using the model of
      trauma-informed care. The student's case suggests that discussing sexual violence
      is imperative for one's own healing and contribution to the nursing profession.

PMID- 27023892
TI  - A Mixed-Methods Study of Prelicensure Nursing Students Changing Answers on
      Multiple Choice Examinations.
AB  - BACKGROUND: Students often question whether changing answers on multiple choice
      examinations correlates with an increase or decrease in their grades. METHOD: In
      a mixed-methods study, 135 prelicensure nursing students were surveyed. The
      answer response forms were reviewed for erasures. Qualitative data were obtained
      through content analysis of two questions. Quantitative analysis was performed to
      explore the relationships among students' self-reported grade performance, test
      anxiety levels, and how often they changed answers. RESULTS: The themes of Risk,
      Careless Mistakes, Adequate Preparation, Instinct, and Cues From the Test were
      identified when students were asked their opinion on changing answers. The themes
      of Indecisiveness, Test Review, and Rationale emerged when students were asked
      why they changed answers. Students who reported being somewhat anxious had a
      greater tendency to change answers. Answers were changed from incorrect to
      correct 55.6% of the time. CONCLUSION: On average, changing answers resulted in a
      moderate increase in test scores.

PMID- 27023893
TI  - The Relationship Between the California Critical Thinking Disposition Inventory
      and Student Learning Outcomes in Baccalaureate Nursing Students.
AB  - BACKGROUND: Critical thinking is the foundation for nurses' decision making. One
      school of nursing used the California Critical Thinking Disposition Inventory
      (CCTDI) to document improvement in critical thinking dispositions. METHOD: A
      retrospective study of 96 nursing students' records examined the relationships
      between the CCTDI and learning outcomes. Correlational statistics assessed
      relationships between CCTDI scores and cumulative grade point averages (GPA) and
      scores on two Health Education Systems Incorporated (HESI) examinations. Ordinal
      regression assessed predictive relationships between CCTDI scores and science
      course grades and NCLEX-RN success. RESULTS: First-year CCTDI scores did not
      predict first-year science grades. Senior-year CCTDI scores did not correlate
      with cumulative GPA or HESI RN Exit Exam scores, but were weakly correlated with
      HESI Pharmacology Exam scores. CCTDI scores did not predict NCLEX-RN success.
      CONCLUSION: This study did not identify meaningful relationships between critical
      thinking dispositions, as measured by the CCTDI, and important learning outcomes.
      The results do not support the efficacy of using the CCTDI in nursing education.

PMID- 27023894
TI  - Blended Learning Versus Traditional Lecture in Introductory Nursing
      Pathophysiology Courses.
AB  - BACKGROUND: Currently, many undergraduate nursing courses use blended-learning
      course formats with success; however, little evidence exists that supports the
      use of blended formats in introductory pathophysiology courses. The purpose of
      this study was to compare the scores on pre- and posttests and course
      satisfaction between traditional and blended course formats in an introductory
      nursing pathophysiology course. METHOD: This study used a quantitative, quasi
      experimental, nonrandomized control group, pretest-posttest design. Analysis of
      covariance compared pre- and posttest scores, and a t test for independent
      samples compared students' reported course satisfaction of the traditional and
      blended course formats. RESULTS: Results indicated that the differences in
      posttest scores were not statistically significant between groups. Students in
      the traditional group reported statistically significantly higher satisfaction
      ratings than students in the blended group. CONCLUSION: The results of this study
      support the need for further research of using blended learning in introductory
      pathophysiology courses in undergraduate baccalaureate nursing programs. Further
      investigation into how satisfaction is affected by course formats is needed.

PMID- 27023895
TI  - If You Teach It, They Will Screen: Advanced Practice Nursing Students' Use of
      Screening and Brief Intervention in the Clinical Setting.
AB  - BACKGROUND: In the United States, approximately 30% of adults drink at risky
      levels or meet the criteria for harmful or dependent alcohol use. Screening,
      brief intervention, and referral to treatment (SBIRT) in primary care settings is
      indicated. This study assessed whether knowledge, attitudes, and beliefs about
      SBIRT, evaluated after a three-part, mixed-methods training, predicted whether 21
      family nurse practitioner (FNP) students screened for alcohol use during clinical
      patient encounters. METHOD: After training, students completed a survey and
      documented implementation of SBIRT during their clinical practice-specific
      management courses. RESULTS: FNP students who reported higher levels of perceived
      competence in their posttraining surveys were more likely to screen for alcohol
      in the clinical setting. CONCLUSION: Screening for alcohol misuse and identifying
      patients engaged in hazardous drinking meet important nurse practitioner
      competencies. Further research is needed to explore training programs that
      specifically emphasize activities to increase perceived competence, knowledge,
      and comfort regarding SBIRT.

PMID- 27023896
TI  - Cancer as a Platform for Genetics Education in the Undergraduate Nursing
      Curriculum.
AB  - BACKGROUND: Nursing leaders and governing agencies have long requested more
      genetic content in the undergraduate nursing curriculum. Despite this, evidence
      in the literature detailing how to meet this objective is scarce. METHOD: Using a
      familiar health condition such as cancer, undergraduate nursing students are
      introduced to the multiple genetic abnormalities that underlie the cellular
      dysregulation leading to carcinogenesis. RESULTS: Nursing students complete the
      course with a knowledge of cancer and its genetic underpinnings. CONCLUSION: This
      approach facilitated integration of genetic content in a disease-focused nursing
      course.

PMID- 27023897
TI  - Expanding the Moral Imagination: The Social Class Dinner.

PMID- 27023899
TI  - [Not Available].

PMID- 27023898
TI  - Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence:
      Comprehensive Review of Evidence.
AB  - Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide,
      but pharmacological treatments for them are underused, despite evidence of
      efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in
      one or more region for the treatment of AUD. Baclofen currently has a temporary
      indication in France. Safety considerations for using psychopharmacological
      treatments in this patient group include the impact of concurrent alcohol
      consumption at high levels; multiple physical comorbidities that may interfere
      with pharmacological effects, distribution and metabolism; and concomitant
      medication for the treatment of comorbid physical and psychiatric conditions. The
      five drugs, including an extended-release injectable suspension of naltrexone,
      have different safety profiles that need to be balanced with the treatment
      objective (initiation or continuation of abstinence, or reduction of drinking),
      individual patient preferences and comorbid conditions. Appropriate treatment
      will be based on the unique risk-benefit profile in each case.

PMID- 27023901
TI  - Early Sitting in Ischemic Stroke Patients (SEVEL): A Randomized Controlled Trial.
AB  - BACKGROUND: Extended immobility has been associated with medical complications
      during hospitalization. However no clear recommendations are available for
      mobilization of ischemic stroke patients. OBJECTIVE: As early mobilization has
      been shown to be feasible and safe, we tested the hypothesis that early sitting
      could be beneficial to stroke patient outcome. METHODS: This prospective
      multicenter study tested two sitting procedures at the acute phase of ischemic
      stroke, in a randomized controlled fashion (clinicaltrials.org registration
      number NCT01573299). Patients were eligible if they were above 18 years of age
      and showed no sign of massive infarction or any contra-indication for sitting. In
      the early-sitting group, patients were seated out of bed at the earliest possible
      time but no later than one calendar day after stroke onset, whereas the
      progressively-sitting group was first seated out of bed on the third calendar day
      after stroke onset. Primary outcome measure was the proportion of patients with a
      modified Rankin score [0-2] at 3 months post stroke. Secondary outcome measures
      were a.) prevalence of medical complications, b.) length of hospital stay, and
      c.) tolerance to the procedure. RESULTS: One hundred sixty seven patients were
      included in the study, of which 29 were excluded after randomization. Data from
      138 patients, 63 in the early-sitting group and 75 in the progressively-sitting
      group were analyzed. There was no difference regarding outcome of people with
      stroke, with a proportion of Rankin [0-2] score at 3 months of 76.2% and 77.3% of
      patients in the early- and progressive-sitting groups, respectively (p = 0.52).
      There was also no difference between groups for secondary outcome measures, and
      the procedure was well tolerated in both arms. CONCLUSION: Due to a slow
      enrollment, fewer patients than anticipated were available for analysis. As a
      result, we can only detect beneficial/detrimental effects of +/- 15% of the early
      sitting procedure on stroke outcome with a realized 37% power. However,
      enrollment was sufficient to rule out effect sizes greater than 25% with 80%
      power, indicating that early sitting is unlikely to have an extreme effect in
      either direction on stroke outcome. Additionally, we were not able to provide a
      blinded assessment of the primary outcome. Taking these limitations into account,
      our results may help guide the development of more effective acute stroke
      rehabilitation strategies, and the design of future acute stroke trials involving
      out of bed activities and other mobilization regimens. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01573299.

PMID- 27023900
TI  - The Coral Trait Database, a curated database of trait information for coral
      species from the global oceans.
AB  - Trait-based approaches advance ecological and evolutionary research because
      traits provide a strong link to an organism's function and fitness. Trait-based
      research might lead to a deeper understanding of the functions of, and services
      provided by, ecosystems, thereby improving management, which is vital in the
      current era of rapid environmental change. Coral reef scientists have long
      collected trait data for corals; however, these are difficult to access and often
      under-utilized in addressing large-scale questions. We present the Coral Trait
      Database initiative that aims to bring together physiological, morphological,
      ecological, phylogenetic and biogeographic trait information into a single
      repository. The database houses species- and individual-level data from published
      field and experimental studies alongside contextual data that provide important
      framing for analyses. In this data descriptor, we release data for 56 traits for
      1547 species, and present a collaborative platform on which other trait data are
      being actively federated. Our overall goal is for the Coral Trait Database to
      become an open-source, community-led data clearinghouse that accelerates coral
      reef research.

PMID- 27023902
TI  - A Novel Blocking ELISA for Detection of Antibodies against Hepatitis E Virus in
      Domestic Pigs.
AB  - Hepatitis E virus (HEV) infects both humans and animals, with an overall human
      mortality rate generally less than 1%, but as high as 20% among pregnant women.
      HEV strains fall into 4 major genotypes. Zoonotic genotypes 3 and 4 associate
      with sporadic human and animal HEV cases in many industrialized countries. To
      date, collective evidence implicates pigs as the main HEV reservoir, justifying
      the importance of monitoring HEV infection rates in pig herds to prevent human
      illness. Due to the lack of a robust in vitro cell culture system for viral
      propagation, no "gold standard" assay has yet been developed to detect HEV
      infection in domestic pigs. 1E4, a monoclonal antibody (mAb) specific for the C
      terminal 268 amino acids of HEV genotype 4 ORF2 capsid protein (sORF2-C), was
      generated and conjugated to horseradish peroxidase (HRP) for use in a blocking
      ELISA (bELISA). Optimal sORF2-C coating antigen concentration (8 MUg/ml), HRP-1E4
      dilution (1:1000), and test pig serum dilution (1:20) were determined using a
      checkerboard titration test. A cut-off value of 16.9% was chosen to differentiate
      between positive vs. negative sera after mean percent inhibition (PI) testing of
      230 negative pig sera. Compared with the indirect ELISA (iELISA), western blot,
      and a commercial ELISA kit for detecting anti-HEV antibodies in human sera, the
      bELISA showed no statistical differences and statistically high coincidence of
      93.23%, 92%, and 95% with the other tests, respectively. A blocking ELISA
      (bELISA) for detecting anti-HEV antibodies in pig serum samples was developed
      with high sensitivity and high specificity comparable to that of the indirect
      ELISA. The bELISA results exhibited high agreement with iELISA, western blot, and
      a commercial ELISA kit designed to detect human anti-HEV antibodies. Therefore,
      bELISA should serve as an ideal method for large-scale serological investigation
      of anti-HEV antibodies in domestic pigs. 

PMID- 27023905
TI  - A mutation in SLC22A4 encoding an organic cation transporter expressed in the
      cochlea strial endothelium causes human recessive non-syndromic hearing loss
      DFNB60.
AB  - The high prevalence/incidence of hearing loss (HL) in humans makes it the most
      common sensory defect. The majority of the cases are of genetic origin. Non
      syndromic hereditary HL is extremely heterogeneous. Genetic approaches have been
      instrumental in deciphering genes that are crucial for auditory function. In this
      study, we first used NADf chip to exclude the implication of known North-African
      mutations in HL in a large consanguineous Tunisian family (FT13) affected by
      autosomal recessive non-syndromic HL (ARNSHL). We then performed genome-wide
      linkage analysis and assigned the deafness gene locus to ch:5q23.2-31.1,
      corresponding to the DFNB60 ARNSHL locus. Moreover, we performed whole exome
      sequencing on FT13 patient DNA and uncovered amino acid substitution p.Cys113Tyr
      in SLC22A4, a transporter of organic cations, cosegregating with HL in FT13 and
      therefore the cause of ARNSHL DFNB60. We also screened a cohort of small Tunisian
      HL families and uncovered an additional deaf proband of consanguineous parents
      that is homozygous for p.Cys113Tyr carried by the same microsatellite marker
      haplotype as in FT13, indicating that this mutation is ancestral. Using
      immunofluorescence, we found that Slc22a4 is expressed in stria vascularis (SV)
      endothelial cells of rodent cochlea and targets their apical plasma membrane. We
      also found Slc22a4 transcripts in our RNA-seq library from purified primary
      culture of mouse SV endothelial cells. Interestingly, p.Cys113Tyr mutation
      affects the trafficking of the transporter and severely alters ergothioneine
      uptake. We conclude that SLC22A4 is an organic cation transporter of the SV
      endothelium that is essential for hearing, and its mutation causes DFNB60 form of
      HL. 

PMID- 27023906
TI  - Expanding the clinical and genetic heterogeneity of hereditary disorders of
      connective tissue.
AB  - Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the
      connective tissue, primarily that of the skin, joint and vessels, is abnormal,
      although the resulting clinical manifestations can vary widely between the
      different historical subtypes. Many cases of hereditary disorders of connective
      tissue that do not seem to fit these historical subtypes exist. The aim of this
      study is to describe a large series of patients with inherited connective tissue
      disorders evaluated by our clinical genetics service and for whom a likely causal
      variant was identified. In addition to clinical phenotyping, patients underwent
      various genetic tests including molecular karyotyping, candidate gene analysis,
      autozygome analysis, and whole-exome and whole-genome sequencing as appropriate.
      We describe a cohort of 69 individuals representing 40 families, all referred
      because of suspicion of an inherited connective tissue disorder by their primary
      physician. Molecular lesions included variants in the previously published
      disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and
      SPARC with interesting variations on the published clinical phenotypes. We also
      describe the first recessive EDS-like condition to be caused by a recessive
      COL1A1 variant. In addition, exome capture in a familial case identified a
      homozygous truncating variant in a novel and compelling candidate gene, AEBP1.
      Finally, we also describe a distinct novel clinical syndrome of cutis laxa and
      marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of
      vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome
      sequencing of the two families with this new clinical entity. Our study expands
      the clinical spectrum of hereditary disorders of connective tissue and adds three
      novel candidate genes including two that are associated with a highly distinct
      syndrome. 

PMID- 27023907
TI  - A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer.
AB  - Gigaxonin, the product of GAN gene localized to chromosome 16, is associated with
      the early onset neuronal degeneration disease giant axonal neuropathy (GAN).
      Gigaxonin is an E3 ubiquitin ligase adaptor protein involved in intermediate
      filament processing in neural cells, and vimentin filaments in fibroblasts.
      Mutations of the gene cause pre-neural filaments to accumulate and form giant
      axons resulting in the inhibition of neural cell signaling. Analysis of the
      catalog of somatic mutations in cancer, driver DB and IDGC data portal databases
      containing 21,000 tumor genomic sequences has identified GAN patient mutations in
      cancer cell lines and primary tumors. The database search has also shown the
      presence of identical missense and nonsense gigaxonin mutations in GAN and colon
      cancer. These mutations frequently occur in the domains associated with protein
      homodimerization and substrate interaction such as Broad-Complex, Tramtrack and
      Bric a brac (BTB), BTB associated C-terminal KELCH (BACK), and KELCH repeats.
      Analysis of the International HapMap Project database containing 1200 normal
      genomic sequences has identified a single nucleotide polymorphism (SNP),
      rs2608555, in exon 8 of the gigaxonin sequence. While this SNP is present in >40
      % of Caucasian population, it is present in less than 10 % of Japanese and
      Chinese populations. Although the role of gigaxonin polymorphism is not yet
      known, CFTR and MDR1 gene studies have shown that silent mutations play a role in
      the instability and aberrant splicing and folding of mRNAs. We believe that
      molecular and functional investigation of gigaxonin mutations including the exon
      8 polymorphism could lead to an improved understanding of the relationship
      between GAN and cancer.

PMID- 27023908
TI  - Ameliorative effect of melatonin against increased intestinal permeability in
      diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation.
AB  - The increased intestinal permeability and functional impairment play an important
      role in type 2 diabetes (T2D), and melatonin may possess enteroprotection
      properties. Therefore, we used streptozotocin-induced diabetic rat model to
      investigate the regulation of intestinal permeability by melatonin. Rats were
      randomly divided into three groups, including control, diabetes mellitus (DM),
      and DM rats treated with melatonin. Melatonin was administered (10 mg/kg/day) by
      gavage for 24 weeks. The DM rats significantly increased the serum fasting blood
      glucose and lipid levels, which were alleviated by melatonin treatment.
      Importantly, the intestinal epithelial permeability was significantly increased
      in DM rats but was ameliorated following treatment with melatonin. These findings
      also indicated the expression of myosin light chain kinase (MLCK) and
      phosphorylation of MLC targeting subunit (MYPT) induced myosin light chain (MLC)
      phosphorylation level was markedly elevated in hyperglycemic and hyperlipidemic
      status. They were partly associated with down-regulated membrane type 1 and 2
      (MT1 and MT2) expression, and up-regulated Rho-associated protein kinase (ROCK)
      expression and increased extracellular signal-regulated kinase (ERK)
      phosphorylation. However, the changes in target protein expression were reversed
      by melatonin. In conclusion, our results show melatonin beneficial effects on
      impaired intestinal epithelial permeability in T2D by suppressing ERK/MLCK- and
      ROCK/MCLP-dependent MLC phosphorylation. 

PMID- 27023909
TI  - Mitochondrial defects associated with beta-alanine toxicity: relevance to hyper
      beta-alaninemia.
AB  - Hyper-beta-alaninemia is a rare metabolic condition that results in elevated
      plasma and urinary beta-alanine levels and is characterized by neurotoxicity,
      hypotonia, and respiratory distress. It has been proposed that at least some of
      the symptoms are caused by oxidative stress; however, only limited information is
      available on the mechanism of reactive oxygen species generation. The present
      study examines the hypothesis that beta-alanine reduces cellular levels of
      taurine, which are required for normal respiratory chain function; cellular
      taurine depletion is known to reduce respiratory function and elevate
      mitochondrial superoxide generation. To test the taurine hypothesis, isolated
      neonatal rat cardiomyocytes and mouse embryonic fibroblasts were incubated with
      medium lacking or containing beta-alanine. beta-alanine treatment led to
      mitochondrial superoxide accumulation in conjunction with a decrease in oxygen
      consumption. The defect in beta-alanine-mediated respiratory function was
      detected in permeabilized cells exposed to glutamate/malate but not in cells
      utilizing succinate, suggesting that beta-alanine leads to impaired complex I
      activity. Taurine treatment limited mitochondrial superoxide generation,
      supporting a role for taurine in maintaining complex I activity. Also affected by
      taurine is mitochondrial morphology, as beta-alanine-treated fibroblasts undergo
      fragmentation, a sign of unhealthy mitochondria that is reversed by taurine
      treatment. If left unaltered, beta-alanine-treated fibroblasts also undergo
      mitochondrial apoptosis, as evidenced by activation of caspases 3 and 9 and the
      initiation of the mitochondrial permeability transition. Together, these data
      show that beta-alanine mediates changes that reduce ATP generation and enhance
      oxidative stress, factors that contribute to heart failure. 

PMID- 27023910
TI  - TMEM49-related apoptosis and metastasis in ovarian cancer and regulated cell
      death.
AB  - Ovarian cancer is one of the greatest causes of cancer death in women. The
      association of TMEM49 and ovarian cancer is poorly defined. Here, we reported
      that TMEM49 was significantly increased in ovarian tumor tissues compared to
      ovarian normal tissues. Furthermore, down-regulation of TMEM49 through RNA
      interference inhibited cell proliferation and arrested G1/S transition in two
      ovarian cancer cell lines, OVCAR3 and A2780. More importantly, TMEM49 silencing
      induced cell apoptosis. Additionally, down-regulation of TMEM49 in ovarian cancer
      notably repressed cell invasion and adhesion. Further gene set enrichment
      analysis suggested that apoptosis and metastasis up related signal pathways were
      associated with the TMEM49 expression. Western blot revealed that the expression
      of Caspase3, Bad, and Bax were increased, while expression of MMP2, KLF10, and
      CXCL12 were reduced by TMEM49 knockdown. Since expression of TMEM49 seems to be
      associated with the apoptosis and metastasis up signaling pathways of ovarian
      cancer, and suppression of its expression can inhibit cancer cell growth and
      metastasis, TMEM49 may be a potential therapeutic target in human ovarian cancer.

PMID- 27023911
TI  - Disubstituted naphthyl beta-D-xylopyranosides: Synthesis, GAG priming, and
      histone acetyltransferase (HAT) inhibition.
AB  - Xylosides are a group of compounds that can induce glycosaminoglycan (GAG) chain
      synthesis independently of a proteoglycan core protein. We have previously shown
      that the xyloside 2-(6-hydroxynaphthyl)beta-D-xylopyranoside has a tumor
      selective growth inhibitory effect both in vitro and in vivo, and that the effect
      in vitro was correlated to a reduction in histone H3 acetylation. In addition,
      GAG chains have previously been reported to inhibit histone acetyltransferases
      (HAT). To investigate if xylosides, or the corresponding xyloside-primed GAG
      chains, can be used as HAT inhibitors, we have synthesized a series of
      naphthoxylosides carrying structural motifs similar to the aromatic moieties of
      the known HAT inhibitors garcinol and curcumin, and studied their biological
      activities. Here, we show that the disubstituted naphthoxylosides induced GAG
      chain synthesis, and that the ones with at least one free phenolic group
      exhibited moderate HAT inhibition in vitro, without affecting histone H3
      acetylation in cell culture. The xyloside-primed GAG chains, on the other hand,
      had no effect on HAT activity, possibly explaining why the effect of the
      xylosides on histone H3 acetylation was absent in cell culture as the xylosides
      were recruited for GAG chain synthesis. Further investigations are required to
      find xylosides that are effective HAT inhibitors or xylosides producing GAG
      chains with HAT inhibitory effects. 

PMID- 27023912
TI  - Glycosylation is crucial for a proper catalytic site organization in human
      glucocerebrosidase.
AB  - Gaucher disease, an autosomal recessive disorder, is caused by a deficiency of
      glucocerebrosidase (GCase) enzyme, a peripheral membrane-associated glycoprotein
      that hydrolyses glucosylceramide in lysosomes. Glycosylation is essential for the
      development of a catalytically active enzyme, specifically in the first site,
      located at Asn19. However, both the molecular basis of the relevance of N
      glycosylation over GCase activity and the effects of glycosylation over its
      structure and dynamics are still not fully understood. Thus, the present work
      evaluated GCase enzyme in increasing glycosylation content using triplicate
      unbiased molecular dynamics simulations. Accordingly, the N-linked glycan chains
      caused local conformational stabilization effects over the protein, as well as in
      regions flanking the enzyme catalytic dyad. In the case of the Asn19-linked
      glycan, it also occurred around region 438-444, where one of the most prevalent
      GCase mutations is found. Markedly, an increasing catalytic dyad organization was
      related to increasing glycosylation contents, offering the first atomic-level
      explanation for the experimental observation that GCase activity is controlled by
      glycosylation, especially at Asn19. 

PMID- 27023914
TI  - N-Terminal methionine processing by the zinc-activated Plasmodium falciparum
      methionine aminopeptidase 1b.
AB  - The methionine aminopeptidase 1b from Plasmodium falciparum (PfMetAP 1b) was
      cloned, expressed in Escherichia coli and characterized. Surprisingly, and in
      contrast to other methionine aminopeptidases (MetAPs) that require heavy-metal
      cofactors such as cobalt, the enzyme is reliably activated by zinc ions.
      Immobilization of the enzyme is possible by His-tag metal chelation to
      iminodiacetic acid-agarose and by covalent binding to chloroacetamido-hexyl
      agarose. The covalently immobilized enzyme shows long-term stability, allowing a
      continuous, heterogenous processing of N-terminal methionines, for example, in
      recombinant proteins. Activation by zinc, instead of cobalt as for other MetAPs,
      avoids the introduction of heavy metals with toxicological liabilities and
      oxidative potential into biotechnological processes. The PfMetAP 1b therefore
      represents a useful tool for the enzymatic, posttranslational processing of
      recombinant proteins. 

PMID- 27023913
TI  - ULK1 and JNK are involved in mitophagy incurred by LRRK2 G2019S expression.
AB  - Mutations in LR RK2 (Leucine rich repeat kinase 2) are a major cause of
      Parkinson's disease (PD). We and others reported recently that expression of the
      pathogenic gainof-function mutant form of LRRK2, LRRK2 G2019S, induces
      mitochondrial fission in neurons through DLP1. Here we provide evidence that
      expression of LRRK2 G2019S stimulates mitochondria loss or mitophagy. We have
      characterized several LRRK2 interacting proteins and found that LRRK2 interacts
      with ULK1 which plays an essential role in autophagy. Knockdown of either ULK1 or
      DLP1 expression with shRNAs suppresses LRRK2 G2019S expression-induced
      mitochondrial clearance, suggesting that LRRK2 G2019S expression induces
      mitochondrial fission through DLP1 followed by mitophagy via an ULK1 dependent
      pathway. In addition to ULK1, we found that LRRK2 interacts with the endogenous
      MKK4/7, JIP3 and coordinates with them in the activation of JNK signaling.
      Interestingly, LRRK2 G2019S-induced loss of mitochondria can also be suppressed
      by 3 different JNK inhibitors, implying the involvement of the JNK pathway in the
      pathogenic mechanism of mutated LRRK2. Thus our findings may provide an insight
      into the complicated pathogenesis of PD as well as some clues to the development
      of novel therapeutic strategies. 

PMID- 27023915
TI  - Identification of a type III polyketide synthase involved in the biosynthesis of
      spirolaxine.
AB  - Spirolaxine is a natural product isolated from Sporotrichum laxum ATCC 15155,
      which has shown a variety of biological activities including promising anti
      Helicobacter pylori property. To understand how this compound is biosynthesized,
      the genome of S. laxum was sequenced. Analysis of the genome sequence revealed
      two putative type III polyketide synthase (PKS) genes in this strain, Sl-pks1 and
      Sl-pks2, which are located adjacent to each other (~2.0 kb apart) in a tail-to
      tail arrangement. Disruption of these two genes revealed that Sl-PKS2 is the
      dedicated PKS involved in the biosynthesis of spirolaxine. The intron-free Sl
      pks2 gene was amplified from the cDNA of S. laxum and ligated into the expression
      vector pET28a for expression in Escherichia coli BL21-CodonPlus (DE3)-RIL. The
      major products of Sl-PKS2 in E. coli were characterized as alkylresorcinols that
      contain a C13-C17 saturated or unsaturated hydrocarbon side chain based on the
      spectral data. This enzyme was purified and reacted with malonyl-CoA and a series
      of fatty acyl-SNACs (C6-C10). Corresponding alkylresorcinols were formed from the
      decarboxylation of the synthesized tetraketide resorcylic acids, together with
      fatty acyl-primed triketide and tetraketide pyrones as byproducts. This work
      provides important information about the PKS involved in the biosynthesis of
      spirolaxine, which will facilitate further understanding and engineering of the
      biosynthetic pathway of this medicinally important molecule. 

PMID- 27023916
TI  - Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent
      advances from genome sequencing and experimental studies.
AB  - The polyene macrolide group includes important antifungal drugs, to which
      resistance does not arise readily. Chemical and biological methods have been used
      in attempts to make polyene antibiotics with fewer toxic side effects. Genome
      sequencing of producer organisms is contributing to this endeavour, by providing
      access to new compounds and by enabling yield improvement for polyene analogues
      obtained by engineered biosynthesis. This recent work is also enhancing
      bioinformatic methods for deducing the structures of cryptic natural products
      from their biosynthetic enzymes. The stereostructure of candicidin D has recently
      been determined by NMR spectroscopy. Genes for the corresponding polyketide
      synthase have been uncovered in several different genomes. Analysis of this new
      information strengthens the view that protein sequence motifs can be used to
      predict double bond geometry in many polyketides.Chemical studies have shown that
      improved polyenes can be obtained by modifying the mycosamine sugar that is
      common to most of these compounds. Glycoengineered analogues might be produced by
      biosynthetic methods, but polyene glycosyltransferases show little tolerance for
      donors other than GDP-alpha-D-mycosamine. Genome sequencing has revealed
      extending glycosyltransferases that add a second sugar to the mycosamine of some
      polyenes. NppY of Pseudonocardia autotrophica uses UDP-N-acetyl-alpha-D
      glucosamine as donor whereas PegA from Actinoplanes caeruleus uses GDP-alpha-D
      mannose. These two enzymes show 51 % sequence identity and are also closely
      related to mycosaminyltransferases. These findings will assist attempts to
      construct glycosyltransferases that transfer alternative UDP- or (d)TDP-linked
      sugars to polyene macrolactones. 

PMID- 27023917
TI  - Optical Coherence Tomography Angiography Features of Type 3 Neovascularization in
      Age-Related Macular Degeneration.
AB  - PURPOSE: To characterize the imaging features of type 3 neovascularization
      secondary to exudative age-related macular degeneration on optical coherence
      tomography (OCT) angiography (OCTA). METHODS: Patients diagnosed with treatment
      naive early-stage type 3 neovascularization underwent multimodal imaging,
      including color retinal photography or multicolor imaging, fluorescein
      angiography, indocyanine green angiography, spectral-domain OCT and OCTA. The
      OCTA features of type 3 neovascularization were analyzed and correlated with the
      findings on angiography and spectral-domain OCT. RESULTS: OCTA showed lesions
      characterized by a retinal-retinal anastomosis. These lesions emerged from the
      deep capillary plexus and formed a clear, tuft-shaped, high-flow network in the
      outer retinal segment in all eyes, abutting in the subretinal pigment epithelium
      space. In most cases, a small, clew-like lesion was present in the
      choriocapillaris segment. Moreover, in some cases, this clew-like lesion seemed
      to be connected to the choroid through a small-caliber vessel. CONCLUSION: OCTA
      of treatment-naive type 3 neovascularization shows high-flow, tuft-shaped,
      abnormal outer retinal proliferation that is almost consistently associated with
      a small, clew-like lesion in the choriocapillaris layer.

PMID- 27023918
TI  - Multivariate Analysis of Correspondence between Left Atrial Volumes Assessed by
      Echocardiography and 3-Dimensional Electroanatomic Mapping in Patients with
      Atrial Fibrillation.
AB  - BACKGROUND: Left atrial (LA) enlargement is a predictor of worse outcome after
      catheter ablation for atrial fibrillation (AF). Widely used two-dimensional (2D)
      echocardiography is inaccurate and underestimates real LA volume (LAV). We
      hypothesized that baseline clinical characteristics of patients can be used to
      adjust 2D-ECHO indices of LAV in order to minimize this disagreement. METHODS:
      The study enrolled 535 patients (59 +/- 9 years; 67% males; 43% paroxysmal AF)
      who underwent catheter ablation for AF in three specialized centers. We
      investigated multivariately the relationship between 2D-echocardiographic indices
      of LA size, specifically LA diameter in M-mode in the parasternal long-axis view
      (LAD), LAV assessed by the prolate-ellipsoid method (LAVEllipsoid), LAV by the
      planimetric method (LAVPlanimetry), and LAV derived from 3D-electroanatomic
      mapping (LAVCARTO). RESULTS: Cubed LAD of 106 +/- 45 ml, LAVEllipsoid of 72 +/-
      24 ml and LAVPlanimetry of 88 +/- 30 ml correlated only modestly (r = 0.60, 0.69,
      and 0.53, respectively) with LAVCARTO of 137 +/- 46 ml, which was significantly
      underestimated with a bias (+/-1.96 standard deviation) of -31 (-111; +49) ml, 
      64 (-132; +2) ml, and -49 (-125; +27) ml, respectively; p < 0.0001 for their
      mutual difference. LA enlargement itself, age, gender, type of AF, and the
      presence of structural heart disease were independent confounders of measurement
      error of 2D-echocardiographic LAV. CONCLUSION: Accuracy and precision of all 2D
      echocardiographic LAV indices are poor. Their agreement with true LAV can be
      significantly improved by multivariate adjustment to clinical characteristics of
      patients.

PMID- 27023919
TI  - Theoretical Study on Free Fatty Acid Elimination Mechanism for Waste Cooking Oils
      to Biodiesel over Acid Catalyst.
AB  - A theoretical investigation on the esterification mechanism of free fatty acid
      (FFA) in waste cooking oils (WCOs) has been carried out using DMol(3) module
      based on the density functional theory (DFT). Three potential pathways of FFA
      esterification reaction are designed to achieve the formation of fatty acid
      methyl ester (FAME), and calculated results show that the energy barrier can be
      efficiently reduced from 88.597kcal/mol to 15.318kcal/mol by acid catalyst. The
      molar enthalpy changes (DeltarHm degrees ) of designed pathways are negative,
      indicating that FFA esterification reaction is an exothermic process. The
      obtained favorable energy pathway is: H(+) firstly activates FFA, then the
      intermediate combines with methanol to form a tetrahedral structure, and finally,
      producing FAME after removing a water molecule. The rate-determining step is the
      combination of the activated FFA with methanol, and the activation energy is
      about 11.513kcal/mol at 298.15K. Our results should provide basic and reliable
      theoretical data for further understanding the elimination mechanism of FFA over
      acid catalyst in the conversion of WCOs to biodiesel products.

PMID- 27023920
TI  - The role of patient-provider interactions: Using an accounts framework to explain
      hospital discharges against medical advice.
AB  - The phenomenon of leaving the hospital against medical advice (AMA) despite being
      quite common and associated with significant deleterious health outcomes remains
      inadequately understood and addressed. Researchers have identified certain
      patient characteristics as predictors of AMA discharges, but the patients'
      reasons for these events have not been comprehensively explored. Moreover,
      because the medical authority model dominates this research area, providers'
      experiences of AMA discharges remain unstudied. We examined the AMA discharge
      from a patient-centered perspective by analyzing the content of notes providers
      generate to record such events. We analyzed providers' notes for all inpatients
      with a primary HIV diagnosis (N = 33) that, in 2012, left an urban hospital AMA.
      Applying the Scott and Lyman accounts framework, we identified that the notes
      constituted records of providers' and patients' excuses and justifications for
      failing to meet the expectations of a provider offering patient-centered care and
      a compliant patient receiving care. Alongside the patients' reasons for leaving
      AMA, the notes also revealed the providers' reasons for honoring or discrediting
      the patients' accounts. The style of the accounts and the professional status of
      the notes' authors enabled us to contextualize the production and sharing of AMA
      notes in the hospital hierarchy. Conceptualizing AMA notes as dyadic accounts
      elicited specific factors that challenge the patient-provider relationship, and
      generated insights on how to strengthen it, and thus decrease the rates of AMA
      discharges and their associated health effects. 

PMID- 27023921
TI  - Overexpression of Ran GTPase Components Regulating Nuclear Export, but not
      Mitotic Spindle Assembly, Marks Chromosome Instability and Poor Prognosis in
      Breast Cancer.
AB  - BACKGROUND: Ran GTPase regulates nuclear import, nuclear export, and mitotic
      spindle assembly. The multifunctional involvement of seventeen Ran GTPase
      components in these processes has complicated research into how each contributes
      to cancer development. OBJECTIVE: To assess whether individual and process
      specific misexpression of Ran GTPase components contribute to chromosome
      instability (CIN) and worsen breast cancer patient prognosis. METHODS: Using
      publicly available datasets, we studied the degree of misexpression of all Ran
      GTPase signaling components in breast cancer, assessed their involvement in CIN
      and used four clinical tests to evaluate whether their misregulation may
      constitute independent prognostic predictors. RESULTS: A significant majority of
      Ran GTPase signaling components is overexpressed in breast cancer. Strikingly,
      spindle assembly components are overexpressed and associated with CIN with only
      marginal significance and four independent tests indicate that this does not
      worsen patient outcome. Overexpression of nuclear import components is neither
      CIN-associated nor clinically significant. In sharp contrast, overexpression of
      nuclear export components constitutes a strong independent marker for both CIN
      and poor patient prognosis. We identify Exportin 2/CSE1L, Exportin 3/XPOT,
      Exportin 5/XPO5, and RANBP1 as novel potential targets. CONCLUSIONS: We find that
      overexpression of Ran GTPase components involved in nuclear export, but not
      nuclear import or mitotic spindle assembly, is a strong CIN-associated marker for
      poor breast cancer prognosis. This could mean that increased nuclear export (of,
      for instance, pRb, p53, p73, BRCA1, p21, p27, E2F4, IkappaB, survivin), rather
      than spindle defects, mainly drives CIN and tumorigenesis. Hence, selective
      inhibitors of nuclear export may be effective for treating the most aggressive
      and chromosomally unstable breast cancers.

PMID- 27023923
TI  - Is dream recall underestimated by retrospective measures and enhanced by keeping
      a logbook? An empirical investigation.
AB  - In a recent review, Aspy, Delfabbro, and Proeve (2015) highlighted the tendency
      for retrospective measures of dream recall to yield substantially lower recall
      rates than logbook measures, a phenomenon they termed the retrospective-logbook
      disparity. One explanation for this phenomenon is that retrospective measures
      underestimate true dream recall. Another explanation is that keeping a logbook
      tends to enhance dream recall. The present study provides a thorough empirical
      investigation into the retrospective-logbook disparity using a range of
      retrospective and logbook measures and three different types of logbook.
      Retrospective-logbook disparities were correlated with a range of variables
      theoretically related to the retrospective underestimation effect, and
      retrospective-logbook disparities were greater among participants that reported
      improved dream recall during the logbook period. These findings indicate that
      dream recall is underestimated by retrospective measures and enhanced by keeping
      a logbook. Recommendations for the use of retrospective and logbook measures of
      dream recall are provided.

PMID- 27023922
TI  - Sarcopenia and the Modified Glasgow Prognostic Score are Significant Predictors
      of Survival Among Patients with Metastatic Renal Cell Carcinoma Who are Receiving
      First-Line Sunitinib Treatment.
AB  - BACKGROUND: Cancer cachexia is associated with patient outcomes. OBJECTIVE: The
      objective was to evaluate the effect of cachexia on survival among patients with
      metastatic renal cell carcinoma (mRCC) who had received first-line sunitinib
      treatment. PATIENTS AND METHODS: Seventy-one patients were retrospectively
      evaluated. Sarcopenia was diagnosed using sex-specific cut-offs for skeletal
      muscle index (measured using pre-treatment computed tomography) that were
      adjusted for body mass index. The modified Glasgow prognostic score (mGPS) was
      measured using C-reactive protein (CRP) and albumin levels (mGPS 2: CRP >1.0
      mg/dL and albumin <3.5 g/dL; mGPS 1: CRP >1.0 mg/dL; mGPS 0: CRP <=1.0 mg/dL).
      Progression-free survival (PFS) and overall survival (OS) were analyzed using the
      Kaplan-Meier method and Cox proportional hazard models. RESULTS: Forty-five
      patients (63.4 %) had sarcopenia, with 53 (74.6 %), ten (14.1 %), and eight (11.3
      %) patients having an mGPS of 0, 1, and 2, respectively. Sarcopenia was
      associated with significantly inferior PFS and OS, compared to non-sarcopenic
      patients (PFS: 7.6 vs. 18.2 months, p = 0.0004; OS: 22.3 months vs. not reached,
      p = 0.0019). Higher mGPS was associated with inferior PFS and OS (mGPS 0, 1, and
      2: PFS = 11.5, 10.9, and 4.12 months, p < 0.0001; OS = 47.2, not reached, and
      5.28 months, p < 0.0001; respectively). Sarcopenia was an independent predictor
      of shorter PFS (p = 0.0163), and mGPS was an independent predictor of shorter OS
      (p = 0.0012). CONCLUSION: Sarcopenia and mGPS can predict outcomes among patients
      with mRCC who are receiving first-line sunitinib treatment.

PMID- 27023924
TI  - Biodegradation and chemical precipitation of dissolved nutrients in anaerobically
      digested sludge dewatering centrate.
AB  - The objective of this research was to assess specific side-stream treatment
      processes for biodegradation and precipitation of dissolved nutrients in
      dewatering centrate. In this study, characterization was made of a conventional
      suspended growth deammonification treatment process for transforming dissolved
      polyphosphate (poly-P), dissolved organic phosphorus (DOP) and dissolved organic
      nitrogen (DON) in two types of dewatering centrate. The deammonification process
      was configured as a sequencing batch reactor (SBR), combining partial
      nitrification and anaerobic ammonia oxidation (anammox) in a single tank. The
      first centrate feed studied was from the full-scale Annacis Island wastewater
      treatment plant (AIWWTP) located in Metro Vancouver, Canada. The second centrate
      feed was from a lab-scale anaerobic digester (AD) fed waste sludge from the
      existing City of Kelowna Wastewater Treatment Facility (KWTF), located in the
      Okanagan Valley, Canada. In addition, poly aluminum chloride (PACL) dosing was
      assessed for final polishing of dissolved nutrients. The deammonification SBR
      (DeSBR) process showed similar treatment characteristics for both the KWTF and
      AIWWTP centrates with excellent DON removal and poor non-reactive dissolved
      phosphorus (NRDP) removal. A statistical comparison of the DOP and poly-P through
      the DeSBR process suggests that DOP has a higher biodegradation potential. Future
      research focused on understanding the variables associated with degradation of
      DOP could lead to better NRDP removal through deammonification processes.
      Utilization of a post-anammox PACL chemical dosing stage can achieve the
      objective of precipitating any residual DON and NRDP and producing an effluent
      that has lower dissolved nutrients than the pre-digestion KWTF dewatering
      centrate scenario.

PMID- 27023925
TI  - Increasing sulfate concentrations result in higher sulfide production and
      phosphorous mobilization in a shallow eutrophic freshwater lake.
AB  - Increasing sulfate input has been seen as an issue in management of aquatic
      ecosystems, but its influences on eutrophic freshwater lakes is not clear. In
      this study, it was observed that increasing sulfate concentration without
      additional cyanobacterial bloom biomass (CBB) addition did not have an obvious
      effect on element cycling during 1-year continuous flow mesocosm experiments in
      which water and sediments were taken from a shallow eutrophic lake with sulfate
      levels near 1 mM. However, following addition of CBB to mesocosms, sulfate
      reducing bacteria (SRB) were observed in the water column, and increasing numbers
      of SRB in the water column were associated with higher sulfate input. Sulfate
      amendment (0-70 mg L(-1)) also resulted in a larger amount of total dissolved
      sulfide (peak values of 5.90 +/- 0.36 to 7.60 +/- 0.12 mg L(-1)) in the water
      column and acid volatile sulfide (1081.71 +/- 69.91 to 1557.98 +/- 41.72 mg kg(
      1)) in 0-1 cm surface sediments due to sulfate reduction. During the period of
      CBB decomposition, increasing sulfate levels in the water column were positively
      correlated with increasing diffusive phosphate fluxes of 1.23 +/- 0.32 to 2.17 +/
      0.01 mg m(-2) d(-1) at the water-sediment interface. As increases in sulfide and
      phosphate release rates deteriorated the water quality/ecosystem and even spurred
      the occurrence of a black water problem in lakes, the control of sulfate input
      level should be considered for shallow eutrophic lake management, especially
      during cyanobacterial bloom periods.

PMID- 27023926
TI  - Determining the 95% limit of detection for waterborne pathogen analyses from
      primary concentration to qPCR.
AB  - The limit of detection (LOD) for qPCR-based analyses is not consistently defined
      or determined in studies on waterborne pathogens. Moreover, the LODs reported
      often reflect the qPCR assay alone rather than the entire sample process. Our
      objective was to develop an approach to determine the 95% LOD (lowest
      concentration at which 95% of positive samples are detected) for the entire
      process of waterborne pathogen detection. We began by spiking the lowest
      concentration that was consistently positive at the qPCR step (based on its
      standard curve) into each procedural step working backwards (i.e., extraction,
      secondary concentration, primary concentration), which established a
      concentration that was detectable following losses of the pathogen from
      processing. Using the fraction of positive replicates (n = 10) at this
      concentration, we selected and analyzed a second, and then third, concentration.
      If the fraction of positive replicates equaled 1 or 0 for two concentrations, we
      selected another. We calculated the LOD using probit analysis. To demonstrate our
      approach we determined the 95% LOD for Salmonella enterica serovar Typhimurium,
      adenovirus 41, and vaccine-derived poliovirus Sabin 3, which were 11, 12, and 6
      genomic copies (gc) per reaction (rxn), respectively (equivalent to 1.3, 1.5, and
      4.0 gc L(-1) assuming the 1500 L tap-water sample volume prescribed in EPA Method
      1615). This approach limited the number of analyses required and was amenable to
      testing multiple genetic targets simultaneously (i.e., spiking a single sample
      with multiple microorganisms). An LOD determined this way can facilitate study
      design, guide the number of required technical replicates, aid method evaluation,
      and inform data interpretation.

PMID- 27023928
TI  - Correction: Objective Assessment of Nuclear and Cortical Cataracts through
      Scheimpflug Images: Agreement with the LOCS III Scale.

PMID- 27023927
TI  - [Diagnostic strategy and differential therapeutic approach for cystic lesions of
      the pancreas].
AB  - CLINICAL/METHODICAL ISSUE: Cystic pancreatic lesions (CPL) are diagnosed with
      increasing frequency. Because up to 60% of CPL are classified as malignant or
      premalignant, every CPL should be fully investigated and clarified. Serous CPL
      with low risk of malignancy must be differentiated from mucinous CPL with
      relevant potential malignancy (intraductal papillary mucinous neoplasm IPMN) and
      mucinous cystic neoplasm (MCN) as well as from harmless pseudocysts. STANDARD
      RADIOLOGICAL METHODS: Cross-sectional imaging with computed tomography (CT) and
      magnetic resonance imaging (MRI) plays a crucial role in the diagnostics of CPL.
      METHODICAL INNOVATIONS: An algorithm for the differential diagnostic
      classification of CPL is presented. PERFORMANCE: The connection to the pancreatic
      duct is the key diagnostic criterion to differentiate IPMN from all other CPL. An
      exception to this rule is that pseudocysts can also show a connection to the
      pancreatic duct. A further classification of CPL with no connection to the
      pancreatic duct can be made by morphological criteria and correlation of the
      radiological findings with patient age, sex, history and symptoms. PRACTICAL
      RECOMMENDATIONS: Depending on the diagnosis and hence the malignant potential the
      indications for surgery or watch and wait have to be discussed in an
      interdisciplinary cooperation. Due to its higher soft tissue contrast MRI is
      often superior to CT for depiction of CPL morphology.

PMID- 27023929
TI  - Calcium Acetate/Magnesium Carbonate and Cardiovascular Risk Factors in Chronic
      Hemodialysis Patients.
AB  - BACKGROUND/AIM: Calcium acetate/magnesium carbonate (CaMg) is a recent phosphate
      binder that has been shown to have protective cardiovascular (CV) effects in
      animal models. The aim of this study was to evaluate the relationship between
      CaMg therapy and CV risk markers like pulse pressure (PP), left ventricular mass
      index (LVMI) and valvular calcifications compared to sevelamer or no phosphate
      binder (NPB) therapy in chronic hemodialysis (HD) patients. METHODS: We performed
      a 48-month prospective study in 138 HD patients under hemodiafiltration with a
      dialysate Mg concentration of 0.5 mmol/l. Patients underwent treatment with CaMg
      or sevelamer for at least 36 months or NPB therapy. Demographic, clinical,
      biochemical and echocardiographic parameters were evaluated at baseline and after
      a 48-month period. RESULTS: At the end of the study, patients who had taken CaMg
      showed a significant reduction in PP (p < 0.001), LVMI (p = 0.003), aortic (p =
      0.004) and mitral valve calcifications (p = 0.03) compared with NPB patients.
      Patients under CaMg showed a significant reduction of PP (p < 0.001), LVMI (p =
      0.01) and aortic valve calcifications (p = 0.02) compared to sevelamer patients.
      In a multivariable analysis, CaMg therapy was negatively associated with
      progression of LVMI (p = 0.02) and aortic valve calcifications (p = 0.01).
      Patients under CaMg showed higher serum Mg levels (0.93 +/- 0.14 mmol/l) compared
      to patients under sevelamer (0.87 +/- 0.13) or NPB patients (0.82 +/- 0.12; p <
      0.001). CONCLUSIONS: In prevalent HD patients, the use of CaMg over 48 months was
      associated with a reduction of PP and LVMI and with a stabilization of aortic
      valve calcifications. These protective and promising results of this new
      phosphate binder need to be confirmed in randomized controlled studies.

PMID- 27023931
TI  - Testosterone, aging, and the mind.

PMID- 27023930
TI  - Seeing Silver in the Spectrum: LGBT Older Adult Health, Aging, and Gerontological
      Nursing Research.

PMID- 27023932
TI  - Red meat and colon cancer.

PMID- 27023933
TI  - Siestas and your heart: can you nap your way to health?

PMID- 27023935
TI  - The benefits of good connections.  Strong relationships with others can improve
      our health and help us live longer.

PMID- 27023936
TI  - Stepping out with a cane.  When injury, disability, or balance problems threaten
      to sideline you, the right cane can keep you safely on the go.

PMID- 27023934
TI  - On call. I know that smoking is very bad for me. I've cut down to one cigarette
      after lunch and another after dinner each day, with two or three more on most
      Friday and Saturday nights when I socialize. I really enjoy smoking, but I want
      to know if I'm harming myself.

PMID- 27023938
TI  - What to do about warts.  Ugly and annoying, warts never go away fast enough. 
      Several steps may help speed their departure.

PMID- 27023937
TI  - How to treat troublesome fibroids.  The options for treating fibroids are
      numerous and varied.  Here's help in finding what's best for you.

PMID- 27023939
TI  - By the way, doctor.  Every year, I gain about 5 pounds over the holidays.  And
      every year, its gets harder to take them off.  Do you have any suggestions for
      avoiding weight gain this season?

PMID- 27023940
TI  - Dementia: 'Wandering'what to do.

PMID- 27023941
TI  - Help for hearing loss: what works?

PMID- 27023942
TI  - Don't miss a beat treating atrial fibrillation.

PMID- 27023944
TI  - When "normal" is not enough.

PMID- 27023943
TI  - Old drugs, new warnings? Avandia and Actos.

PMID- 27023945
TI  - Mini strokes are a maxi problem.  Treat a transient ischemic attack with the same
      urgency as chest pain.

PMID- 27023946
TI  - Angiotensin inhibitor or blocker?  For controlling blood pressure, an ACE
      inhibitor is a good place to start.

PMID- 27023947
TI  - Surgery or angioplasty for opening a clogged neck artery? For now, surgery is the
      best choice for most people with a narrowed carotid artery.

PMID- 27023948
TI  - Triglycerides: a big fat problem.  This forgotten fat is a source of confusion-
      and heart disease.

PMID- 27023950
TI  - Pedometer-powered walking.

PMID- 27023949
TI  - Sexy supplements can be bad for the heart.

PMID- 27023951
TI  - The ups and downs of folic acid fortification.  During our reproductive years,
      extra folic acid is essential.  After that, it may be too much.

PMID- 27023952
TI  - "No-bones" calculator can help predict hip fracture risk.

PMID- 27023954
TI  - Floaters, flashes, and retinal tears. Seeing things? Usually it's just the
      harmless "stuff" of age-related eye changes, but occasionally it's a sign of
      something more serious.

PMID- 27023953
TI  - Combating MRSA: the drug-resistant "superbug."  Bacteria that don't succumb to
      the usual antibiotics give everyone the jitters.  But there's a lot we can do to
      keep the upper hand.

PMID- 27023955
TI  - Four small lifestyle changes can mean an extra 14 years.

PMID- 27023956
TI  - By the way, doctor.  I'm 26 and positive for HPV.  Is there any point in my
      getting the new HPV vaccine?

PMID- 27023958
TI  - Autism spectrum disorders. . . how common?

PMID- 27023957
TI  - By the way, doctor.  What can you tell me about the side effects of lithium? 
      I've heard it causes thyroid and memory problems.

PMID- 27023959
TI  - . . . Encouraging news about interventions. . .

PMID- 27023960
TI  - . . . And the "final word" on the role of vaccines as a cause of autism.

PMID- 27023961
TI  - More caution on products containing BPA.

PMID- 27023962
TI  - Stuttering may be linked to specific genes.

PMID- 27023963
TI  - FDA warns of confusion over Maalox products.

PMID- 27023964
TI  - Product recalls.  Recalls: Generation 2 Worldwide and "ChildESIGNS" drop side
      crib brands.

PMID- 27023965
TI  - Stress fractures.  Don't fight the pain.

PMID- 27023966
TI  - Health tips.  Walker safety.

PMID- 27023967
TI  - Beans may help lower blood sugar.

PMID- 27023968
TI  - Normal vitamin D level impacts lymphoma outcomes.

PMID- 27023970
TI  - Nutrition after surgery.  When eating isn't easy.

PMID- 27023969
TI  - Kidney cancer treatment.  Advances in specialized procedures.

PMID- 27023971
TI  - Tendon trouble.  New treatment uses enhanced plasma.

PMID- 27023973
TI  - Is watching television really all that bad for you?

PMID- 27023972
TI  - What's the best way to stop a nosebleed?

PMID- 27023974
TI  - Making sense of the breast cancer screening debate.

PMID- 27023976
TI  - Hear here: banishing the sounds of silence.

PMID- 27023975
TI  - The heart of psoriasis.

PMID- 27023977
TI  - Brushing up on your prostate knowledge.

PMID- 27023979
TI  - I've never had chicken pox.  Should I get vaccinated for shingles?

PMID- 27023978
TI  - My doctor has prescribed Chantix to help me quit smoking.  Should I be concerned
      about the side effects?

PMID- 27023980
TI  - Cultivating your inner boss. Memory gets most of the attention, but executive
      function is another part of thinking affected by aging.

PMID- 27023981
TI  - Understanding migraine. 6 frequently asked questions about this infamous type of
      headache.

PMID- 27023983
TI  - Good news: bowel prep not needed.

PMID- 27023982
TI  - Sleep apnea: keeping up the positive pressure.  Many people have trouble sticking
      with the main treatment, the continuous positive airway pressure machines that
      keep airways open.

PMID- 27023984
TI  - More on Kegels: two ways to tighten up.

PMID- 27023985
TI  - Negative news on platelet-rich plasma therapy.

PMID- 27023986
TI  - By the way, doctor. I have a mild case of celiac disease. Do the villi ever
      recover after wheat gluten is given up? I am really tired of gluten-free food!

PMID- 27023987
TI  - By the way, doctor.  Do the contrast agents used with MRI scans have side
      effects?  I have had several MRIs and am wondering if there's reason to be
      worried.

PMID- 27023988
TI  - Ask the doctor. I have been arguing with a friend about whether the statin drugs
      lower blood pressure.  Do they, or don't they?

PMID- 27023989
TI  - Ask the doctor.  Are there any noninvasive, radiation-free tests that can give a
      doctor the same information about possible blockages in my coronary arteries as a
      nuclear stress test?  I've had so many CT scans for other conditions that I'd
      prefer to go non-nuclear for a while.

PMID- 27023990
TI  - Creating a family health history.

PMID- 27023992
TI  - Is sleep apnea taking your breath away?

PMID- 27023991
TI  - Reclaim control: physical therapy for incontinence.

PMID- 27023993
TI  - What to expect after joint replacement surgery.

PMID- 27023995
TI  - I recently started distance running, but I've heard too much might be bad for my
      heart.  Is this true?

PMID- 27023994
TI  - I'm considering vertebroplasty for fractures from osteoporosis, but I've read
      that the procedure isn't very effective.  Should I be concerned?

PMID- 27023996
TI  - Prevention.  90 percent of HIV strains stopped by 2 antibodies.

PMID- 27023997
TI  - Policy.  Testing key to identifying new cases, but HIV clinics face funding short
      fall.

PMID- 27023998
TI  - Transmission.  Jail-based testing plays critical role in stopping spread of HIV.

PMID- 27023999
TI  - CDC program aimed at making testing part of routine care.

PMID- 27024000
TI  - Insurance.  Policy did not cover home in cases of sexual misconduct.

PMID- 27024001
TI  - Emotional distress.  Alleged rumors of HIV infection did not violate man's
      rights.

PMID- 27024002
TI  - Not enough evidence to force man to undergo HIV testing.

PMID- 27024003
TI  - Court ordered to review denial of long-term disability benefits.

PMID- 27024004
TI  - Pathological gambling.  Treatments are based on those used to treat addiction.

PMID- 27024005
TI  - Alternatives to antidepressants during pregnancy.  Options include psychotherapy,
      acupuncture, massage, and electroconvulsive therapy.

PMID- 27024006
TI  - Stress and the sensitive gut.  Psychotherapy may help ease persistent
      gastrointestinal distress.

PMID- 27024007
TI  - Large study finds brain training does not improve overall cognitive fitness.

PMID- 27024008
TI  - Why addition causes craving.

PMID- 27024009
TI  - I was half listening to the television the other night and heard something about
      kids dying from the choking game.  What is that?  How can I tell if my child
      might be playing this game?

PMID- 27024010
TI  - New scanning method may detect early signs of Alzheimer's disease.  The technique
      may eventually enable targeted treatment.

PMID- 27024011
TI  - Common pain relievers may increase heart problems.  High-dosage ibuprofen and
      diclofenac linked to elevated risk of death; naproxen, acetaminophen offer
      alternatives.

PMID- 27024012
TI  - Focused therapy may ease fibromyalgia pain.  Combination of customized behavioral
      therapy and exercise may be key to symptom relief.

PMID- 27024013
TI  - The diabetes-cancer association. The most significant preventive action may lie
      in our own hands, since modifiable risk factors contribute to both diseases.

PMID- 27024014
TI  - More reason to use it or lose it.  Physical activity at almost any level of
      fitness increases fat-burning metabolites and reduces oxidative stress.

PMID- 27024015
TI  - Should I take multivitamins?  I'm a 65-year-old woman, in good health, and follow
      a healthy diet and exercise lifestyle.

PMID- 27024016
TI  - I work at a computer all day and I've developed carpal tunnel syndrome in my
      right (computer mouse) hand.  Short of surgery, is there anything I can do for
      this condition?

PMID- 27024017
TI  - What's the difference between "atrial fibrillation" and "atrial flutter"? I've
      heard them used interchangeably but I thought atrial flutter was a less serious
      condition.

PMID- 27024019
TI  - Legislative barriers hinder progress in opt-out testing.  Non-HIV doctors need
      education on opt-out.

PMID- 27024020
TI  - Q&A on one-minute HIV test approval.

PMID- 27024021
TI  - Once daily pill yields higher ART adherence. Study looked at marginalized
      populations.

PMID- 27024018
TI  - Great results from iPrEx study add to trifecta of good news on prevention.
      Truvada PrEP provided protection in MSM+transgender.

PMID- 27024022
TI  - Abstract and commentary.  A key host response to HIV infection.

PMID- 27024023
TI  - Don't test, don't know: the danger of denial. 1 in 5 MSM has HIV--44% unaware.

PMID- 27024024
TI  - FDA notifications.  Tessamorelin approved for lipodystrophy.

PMID- 27024025
TI  - FDA notifications.  Pediatric abacavir tablets approved.

PMID- 27024026
TI  - FDA notifications. Nominations open for Antiviral drug panel.

PMID- 27024027
TI  - FDA notifications.  CDC issues STD treatment update.  Updated information on HIV,
      STDs.

PMID- 27024028
TI  - Are more seniors abusing drugs?

PMID- 27024029
TI  - A different kind of shoulder replacement.

PMID- 27024030
TI  - The limits of screening for heart disease.  For those at intermediate risk or
      with no symptoms, traditional tests may not be enough.

PMID- 27024032
TI  - I don't seem to be able to smell foods and flowers as well as I used to.  Is
      there anything I can do to bring back my sense of smell?

PMID- 27024031
TI  - Consultation corner.  Redefining Alzheimer's disease.  How new diagnostic
      criteria may speed up the search for a cure.

PMID- 27024033
TI  - I'm getting a hearing aid soon. But I've heard that getting used to it will be
      difficult. What can I do to make wearing a hearing aid easier?

PMID- 27024034
TI  - Meat or beans: what will you have?  Part I: meat.

PMID- 27024036
TI  - Exercising to relax.

PMID- 27024035
TI  - Testosterone replacement: a cautionary tale.

PMID- 27024037
TI  - On call. I am a 72-year-old male in excellent health. I have been diagnosed with
      a 3.7-centimeter aortic aneurysm. My doctor recommends an ultrasound every six
      months. Are six-month checks adequate? And when should surgery be considered?

PMID- 27024038
TI  - The vitamin D-cision brings surprises.  New dietary standards are more cautious
      than many expected.

PMID- 27024039
TI  - Mindful eating.  Slow down, you're eating too fast.  Distracted, hurried eating
      may add pounds and take away pleasure.

PMID- 27024040
TI  - Update from the cold front.  There's no cure in sight, but there do seem to be
      ways to make the common cold less common.

PMID- 27024041
TI  - Understanding the ECG: reading the waves.

PMID- 27024042
TI  - Palliative care: sooner may be better. Early introduction of palliative care
      (well before hospice) improves mood and quality of life--and may help people live
      longer.

PMID- 27024044
TI  - Treatment.  Earlier initiation of HAART should be highest priority.

PMID- 27024043
TI  - Ask the doctor.  My teenage daughter wants to be tan when we go down to Florida
      for our winter vacation in February.  I have suggested one of these so-called
      sunless tanning products, but she says they don't look natural and wants to go to
      an indoor tanning salon instead.  What do you think?

PMID- 27024045
TI  - Research.  Expanding HIV screening program would be cost-effective, experts say.

PMID- 27024046
TI  - Prevention.  South African school program reduces risky behaviors in teens.

PMID- 27024047
TI  - Young gay men at increased risk.

PMID- 27024048
TI  - Man's invasion of privacy claims against hospital time barred.

PMID- 27024049
TI  - Prisons.  No abuse of discretion in sentencing for HIV-positive inmate.

PMID- 27024050
TI  - SSI.  ALJ failed to evaluate fatigue in disability determination.

PMID- 27024051
TI  - Habeas corpus.  Petition denied for man who had sex without disclosing HIV.

PMID- 27024053
TI  - Protect and Respect helps HIV+ women with condoms.  Focus is on addressing their
      life issues too.

PMID- 27024052
TI  - HIV prevention efforts mired in patient denial, physician discomfort. Some 'HIV
      doctors still have a little discomfort talking about sex'.

PMID- 27024054
TI  - Our Q&A with new AIDS United CEO. Advocacy, funding organizations merge in 2011.

PMID- 27024055
TI  - Abstract & commentary.  Time for pre-exposure prophylaxis for HIV?

PMID- 27024056
TI  - FDA notifications.  New etravirine tablet approved by FDA.

PMID- 27024057
TI  - FDA notifications. Once daily dosing of darunavir approved.

PMID- 27024058
TI  - FDA notifications.  Comment period open on guidance for INDs.

PMID- 27024059
TI  - FDA notifications.  Comment period open on combination drugs.

PMID- 27024060
TI  - FDA notifications.  New Zerit labeling approved.

PMID- 27024061
TI  - Newspaper group vows to engage blacks in HIV fight. 'We are at a crossroads'.

PMID- 27024062
TI  - How hospitals make the grade. What really counts when you're seeking the best
      care.

PMID- 27024063
TI  - Six ways to get your zzzzs each night.

PMID- 27024064
TI  - Kidney dialysis: understanding your options.

PMID- 27024065
TI  - Men, should you try testosterone therapy?

PMID- 27024067
TI  - Job strain and heart disease risk in women. Work-related stress may be a risk
      factor for heart problems. So what do we do about it?

PMID- 27024066
TI  - "Health After 50" index 2010.

PMID- 27024069
TI  - Diverticular disease prevention and treatment.  This common colon condition
      usually produces no symptoms, but it can result in bleeding, pain, and serious
      infection.

PMID- 27024068
TI  - Strange bedfellows: polymyalgia rheumatica and temporal arteritis. Two related
      inflammatory conditions affect different parts of the body.

PMID- 27024070
TI  - What to do about dry skin in winter.  At this time of year, hands may be red,
      rough, and raw, and skin may feel itchy and uncomfortable.

PMID- 27024071
TI  - Report sets new dietary intake for vitamin D and calcium.

PMID- 27024072
TI  - Ask the doctor.  What do you know about taking extra folic acid to boost the
      immune system?

PMID- 27024073
TI  - Ask the doctor.  In your September article about blepharitis, you didn't say
      anything about the best way to remove eye makeup.  Are oil-based products bad for
      this condition?

PMID- 27024075
TI  - Trying to solve mystery of CD8 T cells and HIV.  Some killers cells seem more
      potent.

PMID- 27024074
TI  - Special report: elite suppressors & HIV.  Research into elite suppressors offers
      clues to new treatments. A therapeutic vaccine might be possible.

PMID- 27024076
TI  - Defective virus may explain rare couple.  One LTNP and one elite suppressor.

PMID- 27024078
TI  - 'Compelling evidence' spurs release of data.  A 96% reduction in HIV
      transmission.

PMID- 27024077
TI  - Special report: elite suppressor & HIV. Elite suppressor on chemo? No problem.
      Surprising finding: 'nothing happened'.

PMID- 27024079
TI  - HIV researchers fight rumors, misconceptions.  Groundwork necessary to build
      trust.

PMID- 27024080
TI  - Informed consent or too much info? HIV study raises issues about how much to
      tell.

PMID- 27024081
TI  - FDA notifications.  FDA may expand clinical investigator restrictions.

PMID- 27024082
TI  - FDA notifications.  Nevirapine extended release tab approved.

PMID- 27024083
TI  - Transmission.  Study: ARVs effectively reduce HIV transmission.

PMID- 27024084
TI  - Research.  Success and struggles in 30 years since first reported case of AIDS.

PMID- 27024085
TI  - Survey.  Gay, lesbian teens more likely to engage in risky behaviors.

PMID- 27024086
TI  - A new investment model.

PMID- 27024087
TI  - Disability. Company did not discriminate against HIV-positive trucker.

PMID- 27024088
TI  - SSI.  Man suffered from only mild limitations, denied benefits.

PMID- 27024089
TI  - Patent.  Stanford did not hold patent on new HIV testing method.

PMID- 27024090
TI  - Custody.  Father showed 'disregard' for seriousness of condition.

PMID- 27024091
TI  - HIV resurges where it started three decades ago: MSM.  MSM networks, lax condom
      use driving increases.

PMID- 27024092
TI  - ART effective for HIV prevention in couples.  'A very powerful and desirable
      strategy'.

PMID- 27024093
TI  - Q&A interview:  Ugandan ART study foreshadowed HPTN 052.

PMID- 27024094
TI  - HPV vaccine may prevent anal cancer.

PMID- 27024095
TI  - cART start boosts AIDS-free survival.

PMID- 27024096
TI  - Treatment of HHV-8 disease with antivirals.

PMID- 27024097
TI  - FDA notifications.  New draft guidance on financial disclosure.

PMID- 27024098
TI  - FDA notifications.  Rilpivirine approved for HIV treatment.

PMID- 27024099
TI  - Generalized anxiety disorder.  People who worry about everything--and nothing in
      particular--have several treatment options.

PMID- 27024101
TI  - The psychology of risk perception.  Understanding why certain perils seem more
      perilous than others.

PMID- 27024100
TI  - Recognizing depression in men. Physical complaints, substance abuse, and other
      stealth symptoms may mask the problem.

PMID- 27024102
TI  - Premenstrual mood disturbances increase chances of relapse in women with bipolar
      disorder.

PMID- 27024104
TI  - Commentary.  Safe use of social media: guidance for parents.

PMID- 27024103
TI  - Nicotine replacement therapy may ease agitation for hospitalized patients with
      schizophrenia.

PMID- 27024105
TI  - Music and health.

PMID- 27024106
TI  - Improving surgical results: three low-tech approaches.

PMID- 27024107
TI  - Pot for the prostate?

PMID- 27024108
TI  - On call.  My teenage daughter wants to switch from sugar to honey for health
      reasons.  Is honey really any healthier than sugar?

PMID- 27024109
TI  - How addiction hijacks the brain.  Desire initiates the process, but learning
      sustains it.

PMID- 27024110
TI  - When depression starts in the neck.  Treating an underactive thyroid gland may
      improve mood.

PMID- 27024111
TI  - Expressive writing for mental health.  Putting an experience into words may ease
      stress and trauma.

PMID- 27024112
TI  - Long-term results of deep brain stimulation for depression.

PMID- 27024113
TI  - More evidence that exercise aids the brain.

PMID- 27024115
TI  - New Alzheimer's guidelines define early stages of the disease. Changes in the
      brain are detectable years before devastating memory loss.

PMID- 27024114
TI  - Commentary.  FDA: no link between food colorings and hyperactivity in most
      children.

PMID- 27024116
TI  - Ask the doctor. When you talk about breast cancer screening, why don't you
      mention thermography? I've been using it for several years instead of
      mammography, which uses radiation.

PMID- 27024117
TI  - Ask the doctor.  My hair's been thinning.  Could it be due to simvastatin, which
      I started taking several months ago?

PMID- 27024118
TI  - Experts urge intensive lifestyle measures for lowering triglycerides.

PMID- 27024119
TI  - Are there limits to laser refractive surgery after midlife? The same vision
      changes that make you eager to toss your glasses or contacts can complicate your
      decision about surgery.

PMID- 27024120
TI  - Cognitive behavioral therapy and exercise therapy help ease chronic fatigue
      symptoms.

PMID- 27024121
TI  - Soy may be okay for breast cancer survivors.  Prospective studies show no
      increased risk of recurrence.

PMID- 27024122
TI  - When sweating is too much. Hyperhidrosis can dampen your social life and
      interfere with work.  Fortunately, there are several ways to manage it.

PMID- 27024123
TI  - What to do about bunions.  Painful bunions interfere with walking and exercising.
      You can prevent them from getting worse.

PMID- 27024124
TI  - Are full-body airport scanners safe?  The radiation exposure is extremely small,
      and the cancer risk has been called "truly trivial".

PMID- 27024125
TI  - Statins and lower cholesterol...

PMID- 27024126
TI  - ...But there are alternatives.

PMID- 27024128
TI  - Drugs in the water. Pharmaceutical pollution doesn't seem to be harming humans
      yet, but disturbing clues from aquatic life suggest now is the time for
      preventive action.

PMID- 27024127
TI  - Breaking the fast. The timing and the contents of breakfast make it perhaps the
      most important meal of the day.

PMID- 27024130
TI  - Berry good for health.  Berries are healthful and delicious, even if some of the
      health claims may be a little bit exaggerated.

PMID- 27024129
TI  - Ask the doctor.  There's a lot of publicity about omega-3 fats being beneficial
      for heart, mind, joints, eyes, and so on.  There are over-the-counter products of
      varying size.  So, this is my question: is there a daily upper limit on fish oil
      consumption.

PMID- 27024131
TI  - Berry good for your health. Berries are healthful and delicious, even if some of
      the health claims may be a little bit exaggerated.

PMID- 27024133
TI  - A Q&A with our new board member.

PMID- 27024132
TI  - Deactivating the ICDs of hospice patients.  Turning off these devices can spare
      patients pain and suffering.

PMID- 27024134
TI  - Diagnosing Alzheimer's disease.  New criteria divide the disease into three
      stages.

PMID- 27024135
TI  - Why do vitamins keep on failing in clinical trials?

PMID- 27024136
TI  - 9 things that can affect your vitamin D level.  Weight, warm skin, and the angle
      of the sun are among the determinants.

PMID- 27024137
TI  - Bypass vs. angioplasty. Comparisons have produced mixed results, but the heyday
      for both procedures (especially bypass) may be winding down.

PMID- 27024138
TI  - Ask the doctor.  I have chronic sinusitis and nasal polyps.  I switched doctors
      and the new specialist suggested trying oral steroids, something that my previous
      doctor never mentioned.  What do you think?

PMID- 27024139
TI  - Major depression more likely during perimenopause than during premenopause.

PMID- 27024140
TI  - Ask the doctor.  I have a family history of cardiovascular disease.  Although I
      don't have high blood pressure, high cholesterol, diabetes, or any other risk
      factor, I'm concerned about how my cardiologist is screening me, because women
      can have small-vessel disease and not necessarily arterial disease.  How should I
      be screened?

PMID- 27024141
TI  - Ask the doctor.  I enjoyed your February 2011 article on diverticular disease and
      the fiber content of various foods.  However, could you make some distinctions
      between soluble and insoluble fiber?  Some fiber makes me feel very bloated.

PMID- 27024142
TI  - How to prevent a first-time stroke.  Experts update recommendations: new
      guidelines offer advice for people facing a variety of risk factors and special
      circumstances.

PMID- 27024143
TI  - Spiriva: a new drug treatment for asthma? Tiotropium (Spiriva), a drug prescribed
      for chronic obstructive pulmonary disease (COPD), may provide effective
      preventive care for individuals with moderate to severe asthma.

PMID- 27024145
TI  - Celiac disease and depression.  Feelings of despair have a biological tie to
      celiac disease.  Fortunately, treatments are available.

PMID- 27024144
TI  - Are opioids the right choice for arthritis pain relief?  New research questions
      the safety of opioids for older adults with moderate to severe arthritis pain.

PMID- 27024146
TI  - Rheumatoid arthritis: watch what you eat. Some foods may increase or decrease
      your inflammation. Simple dietary changes may improve your symptoms.

PMID- 27024147
TI  - Could switching from multifocal to single lens glasses help keep me from falling?

PMID- 27024149
TI  - What's the difference between dementia and Alzheimer's disease?

PMID- 27024148
TI  - What are some good bone-strengthening exercises to try?

PMID- 27024150
TI  - Minimally invasive aortic valve surgery shows promise.  Procedure expected to
      become an option for patients too sick for surgery.

PMID- 27024151
TI  - Bone growth gene may lead to new osteoporosis treatments.  The Lrp5 gene aids in
      bone growth and strength as well as bone deterioration, depending on certain
      mutations.

PMID- 27024152
TI  - What you eat significantly impacts your heart health. A low-fat diet, plus more
      fruits, grains, nuts, fish and poultry instead of red meat, yields cardiovascular
      health benefits.

PMID- 27024154
TI  - Keys to happiness: preserving mobility and a social life.  Quality of life is
      also dependent on an optimistic outlook.

PMID- 27024153
TI  - Colorectal cancer: red meat increases risk, fiber decreases it. Diet and
      lifestyle changes could prevent 64,000 cases per year in U.S.

PMID- 27024155
TI  - I keep hearing about "functional foods."  What are they, and what are their
      benefits?

PMID- 27024156
TI  - I've been diagnosed with an enlarged prostate.  What are my treatment options?

PMID- 27024157
TI  - My wife has been taking corticosteroids for asthma for the last several months,
      and she and I both noticed that she has increasing difficulty remembering things.
      Can corticosteroids affect memory?

PMID- 27024158
TI  - Treatment.  Assign nurses to people with HIV, mental illness.

PMID- 27024159
TI  - Reearch.  Study shows PrEP effective means of prevention in heterosexuals.

PMID- 27024160
TI  - HIV testing effort identifies more than 18,000 with infection.

PMID- 27024162
TI  - Prisons.  Court says inmate presented evidence of privacy violation.

PMID- 27024161
TI  - Vulnerability to HIV in Africa.

PMID- 27024163
TI  - SSI.  Doctor's records did not match testimony about disability.

PMID- 27024164
TI  - Regulatory action. County cannot be compelled to mandate porn condom use.

PMID- 27024165
TI  - Criminal transmission.  Fla. court literally interprets definition of sexual
      intercourse.

PMID- 27024166
TI  - Surviving a heart attack: a success story.

PMID- 27024167
TI  - Measuring blood pressure: let a machine do it.  Automating this task could yield
      more accurate blood pressure readings.

PMID- 27024168
TI  - New dietary guidelines offer sketch for healthy eating.  These evolving
      guidelines continue to get better and more helpful.

PMID- 27024169
TI  - Another yellow light for calcium supplements.

PMID- 27024170
TI  - Unexpected benefit for digoxin?

PMID- 27024172
TI  - Heart-health questions stump many.

PMID- 27024171
TI  - Emotional control and the heart.

PMID- 27024173
TI  - Ask the doctor. My doctor told me I have bradycardia. I live at an altitude of
      5,765 feet--would moving to a lower altitude help my heart rate? Recent cardiac
      tests, including a nuclear stress test, were normal. My cardiologist said I did
      not need a pacemaker, and to keep on doing what I've been doing. I used to jog
      five miles a day and now, at age 85, walk three miles a day.

PMID- 27024174
TI  - Ask the doctor.  I had a stent put in several years ago, at age 59.  Thanks to a
      better diet, more exercise, a statin, and niacin, my LDL, HDL, and triglycerides
      are excellent.  My latest nuclear stress test showed some ischemia, even though I
      am not having any symptoms, and the follow up angiogram showed several new
      blockages requiring two additional stents.  I think my cardiologist should order
      tests like apolipoprotein A, LDL particle size and number, etc., to dig more
      deeply into why my coronary arteries keep getting clogged despite my best
      efforts.  Is that a good idea or a waste of time and money?

PMID- 27024175
TI  - AIDS alert special report: HIV physician shortage. Is there a doctor in the
      house? Shortage threatens HIV gains. 'The current HIV medical workforce is in
      trouble'.

PMID- 27024176
TI  - CDC trial: HIV PrEP works for heterosexuals.  A 63% reduction in HIV risk.

PMID- 27024178
TI  - AIDS alert special report: HIV physician shortage.  Physician "grew her own" HIV
      doc for practice.  Volunteer returns as doc with a calling.

PMID- 27024177
TI  - Special report: HIV physician shortage.  National groups look to increase HIV
      doctors.  Increased federal support is top need.

PMID- 27024179
TI  - IAS 2011: AIDS at a watershed moment.  'Remember that history will judge us".

PMID- 27024180
TI  - IAS: 'game changers' must be widely adopted. 'The old dichotomies no longer
      exist'.

PMID- 27024181
TI  - FDA notifications.  HCV virus protease inhibitor is approved.

PMID- 27024182
TI  - Breast cancer: thousands may skip extensive lymph node removal. New study changes
      standard treatment, eliminating lymphedema risk.

PMID- 27024183
TI  - Sleep strategies for COPD.  If COPD symptoms keep you awake, try these sleep
      strategies for relief.

PMID- 27024184
TI  - Special report. In-depth coverage of clinical research affecting older adults.
      The Alexander technique. An alternative therapy for chronic back pain.

PMID- 27024185
TI  - Protect yourself from esophageal cancer. Healthy lifestyle changes may improve
      your odds of preventing this rare but life-threatening cancer.

PMID- 27024186
TI  - Eyedrops for glaucoma: when to begin treatment. Eyedrops that reduce intraocular
      pressure can prevent vision loss whether treatment is begun early or late.

PMID- 27024187
TI  - I have pain and have been vomiting lately due to gallstones.  Do I need to have
      my gallbladder removed?

PMID- 27024188
TI  - I have heart disease.  What precautions should I take with herbal products?

PMID- 27024189
TI  - I'm trying to eat more fresh fruits and veggies, but I have difficulty digesting
      them.  What can I do?

PMID- 27024190
TI  - Knee replacement.  A renewed stance in life.

PMID- 27024191
TI  - Health tips.  Safe home cleaning.

PMID- 27024192
TI  - Walking may help prevent brain shrinkage.

PMID- 27024193
TI  - New risk estimates for rheumatoid arthritis, related diseases.

PMID- 27024195
TI  - Avoiding bedbugs.  Tips for travel.

PMID- 27024194
TI  - Brand vs. generic drugs.  Seeking sensible savings.

PMID- 27024196
TI  - Outer ear infection.  Don't delay care.

PMID- 27024197
TI  - If a trigger point injection can help relax muscles, would it help with my upper
      back muscles, which always seem tense?

PMID- 27024198
TI  - I've seen products to clean or sanitize your toothbrush. Is that really
      necessary?

PMID- 27024199
TI  - Niacin trial stopped early: now what?

PMID- 27024200
TI  - Preventing cancer: are we getting closer? A breast cancer drug raises hope for
      chemoprevention.

PMID- 27024201
TI  - Conversation with a Harvard expert. Dr. David S. Ludwig is a nutrition and
      obesity researcher at Harvard-affiliated Children's Hospital Boston. His research
      has focused on the harmful health effects of high-glycemic load foods. He is
      author of "Ending the Food Fight," a book about children's nutrition and weight.

PMID- 27024202
TI  - Psychotherapy at midlife.  It's never too late to benefit from talk therapy.

PMID- 27024203
TI  - Diagnosing and treating interstitial cystitis.  Also called painful bladder
      syndrome, this frustrating disorder disproportionally affects women.

PMID- 27024204
TI  - Another drug prevents breast cancer in postmenopausal women.

PMID- 27024205
TI  - Fibroid embolization and surgery have similar five-year outcomes.

PMID- 27024206
TI  - Ask the doctor. I'm 70 and in good health. My cholesterol levels a re normal.
      Lately, I've started to get little yellow deposits on my eyelids, which I'm told
      are xanthelasma. What causes these, and how can I get rid of them?

PMID- 27024207
TI  - With rising, a fall in blood pressure.  Some people experience drops in blood
      pressure when they stand up.  Falls are a risk.  But there are often simple ways
      to counter the problem.

PMID- 27024208
TI  - Happy--and healthy--trails to you. Some tips for keeping your vacation medically
      uneventful.

PMID- 27024209
TI  - Moderate drinking--and how to keep it that way. Moderation in all things--maybe
      that is the key to health and happiness. The proverb certainly seems true for
      alcohol consumption.

PMID- 27024210
TI  - Ask the doctor.  I am taking furosemide (Lasix) once a day.  I was told to also
      take potassium pills, but I don't like pills.  Can I replace the potassium pill
      with foods high in potassium?

PMID- 27024211
TI  - Ask the doctor. I often feel like I have a lump of mucus in my throat. In the
      morning, I spit some of it up, but the sensation doesn't go away. What can I do
      about it?

PMID- 27024213
TI  - Protecting youths from online harassment. Cyberbullying and sexting are among the
      risks to be aware of.

PMID- 27024212
TI  - Beyond the "baby blues." Postpartum depression is common and treatable.

PMID- 27024214
TI  - Educating and empowering families.  The "Family-to-Family" program helps people
      cope better with a loved one's mental illness.

PMID- 27024215
TI  - Becoming a better perfectionist. A first step is to turn self-criticism into
      problem solving.

PMID- 27024216
TI  - PACE study suggests cognitive behavioral therapy may help some people with
      chronic fatigue syndrome-- but is no panacea.

PMID- 27024218
TI  - Ask the doctor.  I heard a news story about people using bath salts to get high. 
      How is that possible? My husband and I have two teenagers.  Should we talk with
      them about this?

PMID- 27024217
TI  - Secondhand smoke and the brain.

PMID- 27024219
TI  - COURAGE not followed by action.  Results of landmark trial have little effect on
      use of angioplasty.

PMID- 27024220
TI  - What to do when blood pressure resists control.  Taming resistant hypertension
      requires extra attention from you and your doctor.

PMID- 27024221
TI  - Peripheral artery disease often goes untreated.  Problems in arteries supplying
      the legs, kidneys, and elsewhere pose problems for the heart, too.

PMID- 27024222
TI  - Abundance of fructose not good for the liver, heart.  Another reason to avoid
      foods made with a lot of sugar.

PMID- 27024223
TI  - "Polypill" test raises questions.

PMID- 27024224
TI  - Caution advised on Chantix use.

PMID- 27024225
TI  - Another day in the sun for olive oil?

PMID- 27024227
TI  - Pause in CPR before shock reduces survival.

PMID- 27024226
TI  - Failing hearts linked to broken bones.

PMID- 27024229
TI  - Ask the doctor.  My doctor told me to check my heart rate when I feel certain
      symptoms, but I don't know how yo do it.  Can you explain?

PMID- 27024228
TI  - Ask the doctor. I'm 64 and have had lone atrial fibrillation for about a decade.
      I have an echocardiogram every year to make sure the rest of my heart is okay.
      (It is.) My doctor hasn't prescribed and medications for me, but she wants me to
      take a blood thinner when I hit my 65th birthday. I'd rather not do this. Should
      I follow her recommendation? Also, is it possible that the endurance-type
      exercise regimens I have performed over many years led to my developing lone
      atrial fibrillation?

PMID- 27024230
TI  - How to reduce your triglycerides. American Heart Association recommends a lower
      optimal level.

PMID- 27024231
TI  - Diabetes and sex:  don't give up hope.  Sexual problems are common in people with
      diabetes, but effective treatment is available.

PMID- 27024232
TI  - Calcium supplements: good for bones, bad for the heart? Controversial studies add
      to growing concern about calcium supplements and cardiovascular risk.

PMID- 27024233
TI  - Tai chi for fibromyalgia: a new treatment? The slow, graceful moves of this
      martial art form may help relieve the painful symptoms of fibromyalgia.

PMID- 27024234
TI  - Weight gain from medication. Many common prescription drugs can cause you to pack
      on extra pounds.

PMID- 27024235
TI  - I'm trying to quit smoking.  Should I try e-cigarettes?

PMID- 27024236
TI  - For years I've been walking in the evenings, but I'm still gaining weight.  What
      am I doing wrong?

PMID- 27024238
TI  - Millions are not getting optimal treatment for heart failure.  If they were,
      thousands more patients might be saved.

PMID- 27024239
TI  - Long-term weight gain linked to specific foods & lifestyle habits.  But small
      dietary and lifestyle changes over time can arrest or reverse "weight creep".

PMID- 27024237
TI  - I have arthritis of the knee.  What are the best exercises I can do that won't
      hurt me or do further damage?

PMID- 27024240
TI  - New technology may re-open the world of sound for the hearing impaired.  Advances
      in hearing technology can greatly enhance the quality of sound and reduce
      communication difficulty among those with hearing loss.

PMID- 27024242
TI  - Research reveals possible new weapon against cancer. A three-year study leads
      scientists to a mechanism for gene control linked to cancer.

PMID- 27024241
TI  - Adjusting goals, avoiding self-blame lowers stress for caregivers.  Caring for a
      mentally ill relative demands effective coping strategies.

PMID- 27024243
TI  - I know that we're all warned to eat less meat and more fish and skinless poultry,
      but are there any lean cuts of meat I can eat to satisfy the carnivore in me?

PMID- 27024244
TI  - I've suffered from gastroesophageal reflux disease (GERD) for years.  What are my
      treatment options, and is surgery recommended?

PMID- 27024246
TI  - Peripheral artery disease underdiagnosed and undertreated.  Millions of U. S.
      adults not receiving prevention therapy.

PMID- 27024245
TI  - What can you tell me about a procedure called "minimally invasive surgery" (MIS)
      for knee replacement? I have osteoarthritis in my left knee, and would like to
      explore this option.

PMID- 27024247
TI  - Exercise protects the brain and blood vessels. Study reveals that physical
      activity may help protect against "silent strokes".

PMID- 27024248
TI  - Learn your treatment options if you have heart failure. The right combination of
      medications and devices may help you live longer.

PMID- 27024249
TI  - Is atrial fibrillation the "new epidemic" in heart health? Understanding that the
      condition is a permanent one is an important first step is adjusting life with
      this common arrhythmia.

PMID- 27024250
TI  - Study shows link between high-dose statins and diabetes risk.  But health experts
      caution that the cholesterol-lowering drugs are still a powerful and valuable
      ally against heart disease.

PMID- 27024251
TI  - Smoking cessation necessary to reduce your PAD risk.  Smoking narrows blood
      vessels and raises your heart rate.

PMID- 27024252
TI  - I have two coronary stents, but recently my doctor said I may need stents in a
      different artery soon. Does having multiple stent procedures harm the heart? How
      does a doctor determine the timing of stent placement? And are their advantages
      to waiting?

PMID- 27024253
TI  - Exercise guidelines seem to be geared toward people younger than 65.  I'm 78. 
      What are the exercise recommendations for those of us who are older?

PMID- 27024255
TI  - Health tips.  Posture perk up.

PMID- 27024254
TI  - Hip fracture.  Regaining mobility.

PMID- 27024256
TI  - Even if you exercise, too much sitting is bad for your heart.

PMID- 27024257
TI  - Link between vitamin D levels and depression studied.

PMID- 27024259
TI  - Sleep deprivation.  Not a normal part of aging.

PMID- 27024258
TI  - Stem cell transplant.  Replacing bone marrow.

PMID- 27024260
TI  - Mirror neurons.  Specialized brain cells.

PMID- 27024261
TI  - Is it better to use a hard- or soft-bristled toothbrush for regular brushing.

PMID- 27024262
TI  - A white spot in my lung showed up on a routine chest X-ray.  I assumed it would
      be cancer, but my doctor says it may be something else.  What else could it be?

PMID- 27024263
TI  - Noncardiac chest pain.  Heartburn, not heart attack.

PMID- 27024264
TI  - Health tips.  Helpful cold remedies.

PMID- 27024265
TI  - Massage and your aching back.

PMID- 27024266
TI  - Parkinson's drugs may lead to compulsive behavior.

PMID- 27024267
TI  - Treating high blood pressure.  Fine-tuning your goals.

PMID- 27024268
TI  - Chronic leg wounds. Biologic dressing and healing.

PMID- 27024269
TI  - Graves' disease.  Thyroid in overdrive.

PMID- 27024270
TI  - I've heard that there's a high-dose flu shot available. Is it better for older
      adults than the regular flu shot? Should I ask for the high-dose shot?

PMID- 27024271
TI  - It seems as if my doctor and I have tried just about everything for my chronic
      constipation.  Is there anything new that might be of help?

PMID- 27024272
TI  - Prevention.  Experts urge states to fund infant circumcision.

PMID- 27024273
TI  - Research. Hormonal contraception increases risk of acquiring, spreading HIV.

PMID- 27024274
TI  - Treatment.  Early ART is best, but there is a limit on when it should start.

PMID- 27024275
TI  - Study finds way to reawaken immune response to HIV.

PMID- 27024277
TI  - HIV-positive man failed to show he could pay for housing.

PMID- 27024276
TI  - Tenofovir tablet not effective in preventing HIV in women.

PMID- 27024278
TI  - Contract.  Court dismisses complaint for failure to exhaust remedies.

PMID- 27024279
TI  - Benefits.  Questions exist as to whether policy is covered by ERISA.

PMID- 27024281
TI  - Polymyalgia rheumatica.

PMID- 27024280
TI  - SSI.  Court affirms ALJ's ruling denying benefits to man with HIV.

PMID- 27024282
TI  - Atrial fibrillation: common, serious, treatable.

PMID- 27024283
TI  - On call. I am trying to decide between a radical prostatectomy and radioactive
      seed therapy for my newly diagnosed prostate cancer. All the doctors I've
      consulted say I have very early disease (PSA 4.9, Gleason score 6) and that I
      should be cured either way. I'm basing my decision on side effects, but I need
      more information on one thing I learned about on the Internet, penile shortening.

PMID- 27024284
TI  - In praise of gratitude.  Expressing thanks may be one of the simplest ways to
      feel better.

PMID- 27024285
TI  - Depressed parent, depressed child? Researchers are testing family interventions
      for treatment and prevention.

PMID- 27024286
TI  - Seven common memory problems.  Sometimes it's normal to forget things.  Here is a
      look at the most typical lapses.

PMID- 27024287
TI  - Study suggests how nicotine suppresses appetite.

PMID- 27024289
TI  - Encouraging news about borderline personality disorder.

PMID- 27024288
TI  - Weighing psychotherapy options for social anxiety disorder.

PMID- 27024290
TI  - Study suggests a link between sleep-disordered breathing and later cognitive
      decline.

PMID- 27024291
TI  - Ask the doctor. A friend jokes she is a "chocoholic." Can you really become
      addicted to chocolate or other foods?

PMID- 27024292
TI  - Feet and falling. Taking care of your feet could improve your chances of staying
      on them.

PMID- 27024293
TI  - Now being served, better nutrition advice.  Our Healthy Eating Plate alternative
      to the government's MyPlate.

PMID- 27024294
TI  - Do antidepressants work in the damaged brain? Recent results have been
      discouraging for Alzheimer's disease, but they may help stroke patients in a
      variety of ways.

PMID- 27024295
TI  - Ask the doctor.  My wife has morphea spots on many areas of her body.  We are
      currently treating them with Dovonex cream, which seems to help a little but is
      very expensive.  Do you have a better way to treat this disease?  We have been
      told that very little is known about how to treat it.

PMID- 27024296
TI  - Warfarin alternatives provide doctors and their patients with more options.  The
      commonly used anticoagulant warfarin isn't for everybody, and newer drugs may
      help make sure more people are protected against dangerous blood clots.

PMID- 27024297
TI  - Medicated stents protect arteries against downstream blockage.  A Cleveland
      Clinic study suggests that drug-eluting stents could be altered to help deliver a
      variety of medications to specific locations in your arteries.

PMID- 27024298
TI  - Being slim isn't always a guarantee for heart health.  A recent study found that
      having metabolic syndrome and normal weight is more dangerous than being obese,
      but metabolically healthy.

PMID- 27024299
TI  - Heart rate recovery can be improved with exercise.  Normal heart rate recovery is
      associated with a lower mortality rate because it is a sign of a strong and
      efficient working heart muscle.

PMID- 27024300
TI  - Renal denervation among top innovations for 2012. Cleveland Clinic's annual list
      includes a few breakthroughs coming in cardiovascular health.

PMID- 27024301
TI  - I had some bleeding in my leg when I had a stent put in the first time.  I have
      to get another soon.  How does a doctor decide to go in through the leg or the
      arm?

PMID- 27024302
TI  - I was told I'm "pre-hypertensive." How often should I see my doctor and check my
      blood pressure.  And how often should I have my cholesterol levels or glucose
      levels checked?

PMID- 27024303
TI  - Ask the doctor.  More and more nutrition advice seems to be anti-sugar these
      days. So are artificial sweetners a good alternative?

PMID- 27024305
TI  - Ask the doctor.  I am 70, have had sleep problems, and have started Ambien every
      night.  It seems to be working very well.  Is it okay if I keep on taking it?

PMID- 27024304
TI  - Ask the doctor. I saw Harvard's Healthy Eating Plate and noticed that poultry was
      listed as a healthy protein. I am not surprised that you're recommending fish,
      nuts, or beans. But why poultry?

PMID- 27024306
TI  - Ask the doctor.  Is the chemical BPA just another health scare, or is it really
      something we should be worried about?

PMID- 27024307
TI  - Ask the doctor.  I sprained my ankle pretty badly a few weeks ago and was taken
      to the emergency room.  It took three hours before I saw a doctor.  Why are
      emergency rooms so crowded and the waits so long just to be seen?

PMID- 27024308
TI  - Ask the doctor.  I have wet macular degeneration.  I am trying to decide between
      Avastin and Lucentis.  Which drug is better?

PMID- 27024309
TI  - Ask the doctor. A friend has a condition called gastroparesis. Please explain
      what it is and how it can be treated.

PMID- 27024310
TI  - Ask the doctor. My wife's medication to treat atrial fibrillation recently was
      changed from warfarin to a new drug called Pradaxa. They say that the new
      medicine does not require regular INR tests and is just as effective. Is that so?

PMID- 27024311
TI  - Depression and cardiovascular risk in women. Evidence suggests that depression is
      a treatable risk factor for heart disease and stroke.

PMID- 27024312
TI  - Staying active despite osteoporosis.  There are many ways to play it safe while
      gaining the health benefits of exercise.

PMID- 27024314
TI  - Study elucidates health risks for DES daughters.

PMID- 27024313
TI  - Vaginal estrogen ring helps relieve overactive bladder.

PMID- 27024315
TI  - Ask the doctor.  Should I have my magnesium level checked regularly to make sure
      I'm getting enough for my bones?

PMID- 27024316
TI  - Ask the doctor.  Do vaginal estrogens that are used for vaginal dryness have the
      same risks as estrogen taken orally or by skin patch?

PMID- 27024317
TI  - The overlooked hazards of holiday eating. Don't let foodborne pathogens crash
      your party.

PMID- 27024318
TI  - Advances in breast cancer diagnosis and treatment.  Two new studies reveal novel
      treatments, another explores cell movement's impact on cancer proliferation, and
      another make a case for smaller, faster clinical trials.

PMID- 27024319
TI  - Initiative launched to prevent one million heart attacks and strokes. 
      Multipronged attack against America's no. 1 killer urges increased physician
      patient participation in "ABCS".

PMID- 27024320
TI  - More frequent contact with doctor could help diabetes patients.  Proper control
      of blood sugar, blood pressure, and cholesterol may be linked to how often a
      person visits his physician.

PMID- 27024321
TI  - Fruits and vegetables may bolster verbal memory. A recent study suggests
      antioxidants may help preserve the health of brain cells vulnerable to cognitive
      decline.

PMID- 27024322
TI  - I suffer greatly from sinusitis, and have had several surgeries and many courses
      of antibiotics to treat this condition.  Is there another treatment?

PMID- 27024324
TI  - Is colonoscopy the only option for colon cancer screening, or are there other
      tests?

PMID- 27024323
TI  - What can you tell me about phytochemicals? I've heard that they have many health
      benefits?

PMID- 27024325
TI  - Prevention. FDA approves new HIV vaccine for human trials.

PMID- 27024326
TI  - Research.  Risk of drug overdose significantly higher in HIV-positive population.

PMID- 27024327
TI  - Policy.  Guidelines needed to improve sexual health of teen boys.

PMID- 27024328
TI  - New antiretroviral for kids.

PMID- 27024329
TI  - Study urges inclusion of alcohol use in HIV prevention.

PMID- 27024330
TI  - Veterans.  Former marine could not show HIV was related to service.

PMID- 27024331
TI  - SSI.  Claimant failed to present new evidence in disability claim.

PMID- 27024332
TI  - ADA.  Employer did not discriminate; unaware that man had HIV.

PMID- 27024333
TI  - Jail.  Inmate may have been discriminated against because of HIV.

PMID- 27024334
TI  - Obsessions and compulsions in youths.  Cognitive behavioral therapy alone or
      combined with medication may help.

PMID- 27024335
TI  - Schizophrenia and epilepsy. New evidence suggests that these two brain disorders
      may share biological roots.

PMID- 27024336
TI  - Recognizing and managing delirium.  Sudden confusion, especially in the elderly,
      may be a sign of delirium.

PMID- 27024337
TI  - Taming the frenzy in your brain. A new book offers advice about how to get
      organized.

PMID- 27024338
TI  - Updated guidelines issues for attention deficit hyperactivity disorder (ADHD).

PMID- 27024339
TI  - Mindfulness training helps people quit smoking.

PMID- 27024341
TI  - Three (more) cheers for statins.  A trio of studies bolsters evidence of their
      benefits and long-term safety.

PMID- 27024340
TI  - Ask the doctor.  I got divorced a few months ago.  Recently I was diagnosed with
      depression. A friend suggested I try interpersonal therapy.  She thinks the
      problem is my relationship with my former husband.  I'd never heard of this type
      of therapy.  Could you tell me more about it?

PMID- 27024342
TI  - Teamwork in angioplasty-bypass decisions.  New guidelines clarify the ifs and
      thens, but the choice is yours.

PMID- 27024343
TI  - Fun and exergames: not just for kids anymore.  Video game workouts work pretty
      well, but the initial cost can be substantial.

PMID- 27024344
TI  - HDL cholesterol: is higher really better?  Raising HDL with niacin takes a back
      seat to lowering LDL with statins.

PMID- 27024345
TI  - Small step forward for stem cells, giant leaps remain.  Stem cell type and timing
      of treatment seem to matter most.

PMID- 27024346
TI  - Fixing faulty heart rhythms may help kidneys filter better.

PMID- 27024347
TI  - A direct drug hit with alteplase busts up leg clots.

PMID- 27024348
TI  - News from Medicare: free counseling for heart disease and obesity.

PMID- 27024349
TI  - Which drugs work best for resistant high blood pressure?

PMID- 27024351
TI  - Ask the doctor. I'm a fit 61-year-old who had bypass surgery 15 years ago.
      Recently, I've been having rapid heart-beats (what my doctor calls
      supraventricular tachycardia) during or just after vigorous exercise. Should I
      tone down my exercise?

PMID- 27024350
TI  - Ask the doctor.  Can eggs be part of a balanced heart-healthy diet?

PMID- 27024353
TI  - Medications: no more than necessary.

PMID- 27024352
TI  - Putting more brain in the bank. Cognitive reserve can protect you from the
      effects of Alzheimer's and other diseases that affect the brain.

PMID- 27024354
TI  - Pot smokers can maybe breathe a little easier. Moderate consumption of marijuana
      doesn't adversely affect lung function, according to a recent study.

PMID- 27024355
TI  - Another reason to get out there and get moving!  Vigorous exercise may prevent
      Parkinson's disease and help treat it.

PMID- 27024357
TI  - Q&A about the Healthy Eating Plate.

PMID- 27024356
TI  - Can anxiety cause a heart attack?

PMID- 27024358
TI  - Red, brown, green: urine colors and what they might mean. Departures from the
      familiar yellow are often harmless but should be discussed with a doctor.

PMID- 27024359
TI  - A possible brain food that you've probably never heard of.

PMID- 27024360
TI  - Ask the doctor.  Is it true that you can get a tingling feeling from taking too
      much vitamin B6?

PMID- 27024361
TI  - Ask the doctor. I'm 80, and I exercise or bike for an hour and a half almost
      every day and eat a healthy diet. I recently had a blood lipid assessment, and my
      HDL was 70 and my LDL was 42, But my internist wrote me saying that my LDL was
      too low and that I should cut my dose of atorvastatin from 40 mg to 20 mg a day.
      I also take 2,000 mg of niacin daily. Is there general agreement that one's LDL
      should not go below a certain point? Is mine too low?

PMID- 27024363
TI  - Health tips. Enhancing your relationship.

PMID- 27024362
TI  - Blood vessel stents.  Improving blood flow.

PMID- 27024364
TI  - Mindfulness improves irritable bowel syndrome.

PMID- 27024366
TI  - Mediterranean diet. To your good health.

PMID- 27024365
TI  - Tea, coffee and an antibiotic-resistant 'superbug'.

PMID- 27024367
TI  - Foot orthotics.  Inexpensive is often best.

PMID- 27024368
TI  - Molecular breast imaging.  Seeing past dense breast tissue.

PMID- 27024369
TI  - Doesn't Graves' disease cause bulging eyes? My brother was diagnosed with Graves'
      disease several years ago, but his eyes appear to be unchanged.

PMID- 27024370
TI  - Is weightlifting or resistance training safe for me even though I have high blood
      pressure?

PMID- 27024371
TI  - Stroke.  Recognizing signs, controlling risks.

PMID- 27024373
TI  - A good grilling: answering FAQs about our Healthy Eating Plate.

PMID- 27024372
TI  - Here's a trio of suggestions for enjoying good health.

PMID- 27024374
TI  - Warfarin, diabetes drugs cause emergency hospitalization among the elderly. 
      Overdose and drug interactions are to blame.

PMID- 27024375
TI  - Cold out?  Why you need to wear a hat!

PMID- 27024376
TI  - What is a tailor's bunion?

PMID- 27024377
TI  - &%!!# helps when you are hurting.

PMID- 27024378
TI  - Talking about heart failure.

PMID- 27024379
TI  - Niacin + a statin does not add up to benefit.

PMID- 27024380
TI  - Ask the doctor.  I have been diagnosed with type 2 diabetes and sleep apnea.  Is
      there any connection between the two?

PMID- 27024381
TI  - Ask the doctor.  My doctor says I should switch to generic version of Lipitor,
      but is it really the same as Lipitor?

PMID- 27024382
TI  - The PSA test: what's right for you?

PMID- 27024383
TI  - Coffee and your arteries.

PMID- 27024384
TI  - On call. I've always enjoyed fruit with my breakfast cereal. Over the past year,
      my family seems to have shifted from bananas and strawberries to a steady diet of
      blueberries "because they'll keep you healthy". I love blueberries, but I do miss
      variety. So I want to know if blueberries really are good for our health.

PMID- 27024386
TI  - On call. I was very interested in your December 2011 article on how obesity seems
      to spread through social networks. I understand that it's a new type of research,
      but I wonder if it might have overlooked the possibility that obesity might also
      be spread by an actual virus.

PMID- 27024385
TI  - On call. I recently brought a nice bouquet of flowers for my elderly aunt, who
      was hospitalized for a broken hip. She was quite depressed, and I thought the
      flowers would brighten her day, particularly since she is a dedicated gardner. To
      my surprise, the hospital had a policy against bedside flowers, and I could not
      deliver my gift. What's behind this policy, and is it reasonable?

PMID- 27024387
TI  - Disordered eating in midlife and beyond.  Aging can be a challenge to body image.
      For some women, it may bring on--or rekindle--an eating disorder.

PMID- 27024388
TI  - What to do about nonalcoholic fatty liver disease.  It  once seemed that only
      people who drank excessively were at risk for fatty liver disease.  Not anymore.

PMID- 27024390
TI  - Experts update guidelines for treating essential tremor.

PMID- 27024389
TI  - Healing yourself after injury, illness, or surgery.  A new book outlines what you
      can do to heal as well as possible.

PMID- 27024391
TI  - Ask the doctor.  I have varicose veins and would like to get rid of them. Could
      that lead to venous insufficiency?

PMID- 27024392
TI  - Medications help the heart--if you take them. Teamwork with your doctor can lower
      complexity and cost barriers.

PMID- 27024393
TI  - Another warfarin alternative for stroke prevention in people with a-fib. To
      switch or not is a decision for you and your doctor to make.

PMID- 27024394
TI  - No-surgery aortic valve replacement okay for some, not all.  Seek help from a
      heart team when considering your options.

PMID- 27024395
TI  - Living with an implantable cardioverter-defibrillator.  These high-tech devices
      can save --and change--a person's life.

PMID- 27024396
TI  - "Smart at Heart" bridges the emotional and physical shores of heart health.

PMID- 27024398
TI  - Clots can form in stents years after placement.

PMID- 27024397
TI  - Fruit and veggie diet may offset gentic risk for heart disease.

PMID- 27024399
TI  - Psoriasis again linked to heart disease.

PMID- 27024400
TI  - Ask the doctor.  My systolic blood pressure is high in the morning (about 165),
      but in the evening it drops to below 100.  I am taking two blood pressure
      medications daily and still experiencing seriously low blood pressure at night. 
      What would you suggest?

PMID- 27024401
TI  - Ask the doctor.  I am 76 years old and still get hot flashes.  Is it true that
      women who have hot flashes many years after menopause are more likely to
      experience heart problems than those whose symptoms end early in menopause?

PMID- 27024403
TI  - ED pills and benign prostatic hyperplasia.

PMID- 27024402
TI  - The crucial, controversial carotid artery. Part II: Treatment.

PMID- 27024404
TI  - On call. After smoking for over 15 years, I finally quit eight months ago, but I
      still miss my cigarettes.  I recently heard about electronic cigarettes.  Are
      they safe?

PMID- 27024405
TI  - On call.  I read last month's "On call" column about dietary guidelines and
      caloric percentages, but I'm not a math guy.  Any chance you could put it in
      English for me?

PMID- 27024406
TI  - A diet that builds brain health.  Evidence points to key foods and eating
      patterns for protecting memory.

PMID- 27024407
TI  - The telltale signs of migraine.  How to recognize common and uncommon symptoms.

PMID- 27024408
TI  - Treatment.  Hospital deaths down but some infections on rise.

PMID- 27024409
TI  - Research.  Approval of Gilead's Truvada for PrEP passes first hurdle at FDA.

PMID- 27024410
TI  - More research necessary to develop effective, safe vaccine.

PMID- 27024411
TI  - SSI. Nurse practitioner not considered acceptable medical source.

PMID- 27024412
TI  - Housing.  HIV-positive tenant may proceed with case against landlord.

PMID- 27024413
TI  - Retirement.  Behaviors not synonymous with conditions, court says.

PMID- 27024415
TI  - Update: stem cell benefits getting closer.  Scientists are transforming stem cell
      science into stem cell medicine.

PMID- 27024414
TI  - Criminal.  Court did not err by choosing not to suppress statements.

PMID- 27024416
TI  - Ask the doctor.  I'm 50 years old, and lately I've been wheezing when I play
      tennis.  Can I get asthma at my age?

PMID- 27024417
TI  - Ask the doctor.  I have trouble seeing things clearly at night.  Should I change
      my glasses, or could it be a more serious eye problem?

PMID- 27024418
TI  - No weight loss with exercise? Don't worry, you're still helping your heart.

PMID- 27024419
TI  - Discovery may lessen depression stigma.

PMID- 27024420
TI  - Is vitamin E bad for your bones?  Normal doses are okay; megadoses can be
      dangerous.

PMID- 27024421
TI  - Healthier oils make fried food safer. Research clears vegetable oils, but use
      them wisely.

PMID- 27024423
TI  - Coping better after breast cancer.  Complimentary therapies help psychological
      recovery.

PMID- 27024422
TI  - Healthy heart, healthy prostate.  Exercise and weight loss may also protect
      against cancer.

PMID- 27024424
TI  - Hearing loss: time to get proactive.  Millions may be suffering needlessly.

PMID- 27024425
TI  - Your bonus from fruits and veggies.  Three servings a day may lead to rosier
      complexions.

PMID- 27024426
TI  - What you should know about: metformin.

PMID- 27024427
TI  - Study shows aspirin as effective as warfarin for people with heart failure.

PMID- 27024428
TI  - Omega-3 fatty acids may help protect against Alzheimer's disease.

PMID- 27024429
TI  - Study links long-term air pollution exposure to heart, lung problems.

PMID- 27024430
TI  - Fungus mimics cancer in American southwest.

PMID- 27024431
TI  - Asthma treatment underutilized among older adults.

PMID- 27024432
TI  - Heart treatment designed just for you.  Biomarkers help individualize care for
      heart attack and heart failure.

PMID- 27024433
TI  - Ask the doctors. One year ago when I was flying home from a ski trip, my legs
      were cramped due to luggage under my seat. To make a long story short, I was soon
      found to have a blood clot in my right calf and a small blood clot in my lungs. I
      was treated with warfarin for three months and did just fine. Now I want to take
      a long plane trip to South America, and am wondering whether I need to do
      anything to reduce my risk of another blood clot.

PMID- 27024435
TI  - Caution: watch your radiation exposure.  Here's what you need to keep in mind.

PMID- 27024434
TI  - Ask the doctors. I recently developed atrial fibrillation, and I wonder whether I
      need to take an anticoagulant. I am 81 years old, active, and don't really notice
      when I am in atrial fibrillation. I was taking my pulse every now and then and
      found it to be irregular. My doctor said I was going back and forth between
      normal heart rhythm and atrial fibrillation. I am in normal (sinus) rhythm now,
      but he says I should be on warfarin because I have high blood pressure. What do
      you think?

PMID- 27024436
TI  - Breakthrough in aortic valve treatment.  Transcatheter procedure eliminates
      surgery for some.

PMID- 27024437
TI  - Avoid another hospital stay.  Two simple steps will improve your odds.

PMID- 27024438
TI  - Yes to heartburn meds plus clopidogrel. There's no definitive proof this
      combination is dangerous.

PMID- 27024439
TI  - The art of refining heart risk prediction.  It's all in the numbers; and one
      model comes out the winner.

PMID- 27024440
TI  - Pollution may shorten lifespan.  After a heart attack, living near a major
      roadway could be fatal.

PMID- 27024441
TI  - Stop-smoking drug may be safe.

PMID- 27024442
TI  - FDA approves third weight-loss drug.

PMID- 27024443
TI  - One reason for diabetes identified.

PMID- 27024444
TI  - Step up to better blood pressure.  To stay in the healthy zone, lock in the
      basics and talk to your doctor about escalating your medications.

PMID- 27024447
TI  - Head and neck cancer alert.  Doctors are seeing a wave of cancer in men caused by
      the HPV virus.  What should you do?

PMID- 27024446
TI  - On call.  I'm 64, and I don't have any major health problems, but my sex drive
      just isn't what it used to be.  Should I go to a doctor?

PMID- 27024445
TI  - On call.  Should I take fish oil supplements for my heart?  I've heard it helps
      people who have already had heart attacks.

PMID- 27024448
TI  - Colonoscopy now easier to tolerate.  Bowel prep is much more manageable, and CT
      based 'virtual colonoscopy' may one day allow you to skip that, too.

PMID- 27024449
TI  - Seven ways to get calories under control.  Here are some ways to increase your
      calorie awareness and lay the foundation for successful weight loss.

PMID- 27024450
TI  - Tell your doctor if heart disease runs in the family.

PMID- 27024451
TI  - High-fiber for preventing diverticulosis challenged.

PMID- 27024452
TI  - Study shows female 'advantage' in melanoma survival.

PMID- 27024454
TI  - 8 secrets to a good night's sleep. Tired of feeling tired? Here are some simple
      tips to help you get to sleep.

PMID- 27024453
TI  - PSA testing continues in older men despite advice to stop.

PMID- 27024455
TI  - Ask the doctor.  During a pelvic ultrasound to evaluate uterine fibroids, a
      radiologist found a cyst in one of my kidneys.  Should I be concerned about
      kidney cancer?

PMID- 27024456
TI  - Ask the doctor. I am 65 and recently developed a yeast infection. Aren't these
      infections unusual in postmenopausal women?

PMID- 27024457
TI  - What clinical studies can do for you. Research studies can give you access to
      breakthrough treatments.

PMID- 27024458
TI  - I can't eat that! Food intolerances make dairy and other foods hard to swallow.

PMID- 27024459
TI  - Is your heart out of rhythm? An ICD can be lifesaving, but it can have unique
      risks for women.

PMID- 27024460
TI  - Bisphosphonates may not benefit women's bones long-term.

PMID- 27024462
TI  - Better habits could cut cancer deaths.

PMID- 27024461
TI  - Vitamin E no help for heart failure.

PMID- 27024463
TI  - Study highlights exercise for memory.

PMID- 27024464
TI  - Patients should speak up about what replacement heart valves they prefer.
      Research raises questions about whether some heart patients should get mechanical
      valves instead of bioprosthetic valves, but several factors need to be
      considered.

PMID- 27024466
TI  - Real world heart health guidelines target women. The latest research is based
      more on the average patient rather than the participants in clinical studies.

PMID- 27024465
TI  - Lower your triglyceride levels and cut your stroke risk. Triglycerides don't get
      the attention that LDL and HDL get in determining your total lipid profile, but
      these fats pose real threats to your health.

PMID- 27024467
TI  - Dairy products linked to lower diabetes and heart disease risks. However, the
      protective trans-palmitoleic acid in milk is found in highest concentrations in
      whole milk, so caution is advised.

PMID- 27024468
TI  - Understanding the benefits and risks of cardiac imaging tests. Radiation exposure
      is a concern with some of these diagnostic tests, so have frank discussion with
      your doctor about what tests are necessary for you.

PMID- 27024469
TI  - I recently started using supplemental oxygen because I have chronic obstructive
      pulmonary disease (COPD). I'm still fairly active, but I'm concerned about an
      upcoming mitral valve operation. How will relying more on supplemental oxygen
      affect my heart and circulation?

PMID- 27024470
TI  - At a recent checkup, I was told that I had experienced a mild heart attack though
      I don't recall having any symptoms. What does this mean for my future heart
      health and am I now more likely to have a major heart attack?

PMID- 27024471
TI  - Do multivitamins protect you from disease? Multivitamins may slightly reduce the
      risk of cancer but don't prevent heart disease. Keep the focus on diet, not
      supplements.

PMID- 27024473
TI  - On call.  I see my doctor every year for an annual physical examination.  I
      recently heard that people who have annual physicals don't really live longer. 
      Should I still go?

PMID- 27024472
TI  - On call.  I often receive offers in the mail to perform an ultrasound of my
      carotid arteries.  Should I sign up for a carotid ultrasound?

PMID- 27024474
TI  - The four horsemen of forgetfulness. Consider the most likely causes of memory
      slips before assuming the worst. You may need more sleep.

PMID- 27024475
TI  - Heartburn medication side effects:  should you worry?  Proton pump inhibitors
      (PPIs) are safe for most people, but also have potential risks you should know
      about.

PMID- 27024476
TI  - How to get ready for a new knee.  To speed your recovery and return to daily
      activities as soon as possible, start your rehab before surgery.

PMID- 27024478
TI  - Aerobic exercise eases tiredness from cancer.

PMID- 27024477
TI  - When drugs for erectile dysfunction don't work: what's next? Here are the
      alternatives to oral erectile dysfunction drugs. Solutions are available for most
      men's needs.

PMID- 27024479
TI  - Steroid injections for sciatica:  mild, short-term relief.

PMID- 27024480
TI  - Fish oil does not prevent irregular heart rhythms after surgery.

PMID- 27024481
TI  - No added risk for vision loss after cataract removal.

PMID- 27024482
TI  - Combo tests provide more accurate AD prediction.  Misclassification rate drops
      significantly when tests are used together.

PMID- 27024483
TI  - Rethinking cholesterol management.  Lowering LDL levels is once again the Holy
      Grail, since raising HDL failed to make a difference after all.

PMID- 27024484
TI  - Mammography: to screen or not?  Thirty years after mammography came into
      widespread use, there's continuing controversy over the benefits of screening.

PMID- 27024485
TI  - "Atlas" of T-cells may lead to better vaccines.  Mapping T-cells ultimately could
      provide greater defense against disease.

PMID- 27024486
TI  - Aerobic exercise beats resistance training for weight and fat loss. Physical
      activity, such as walking, running, and swimming, seems best for losing both
      weight and body fat.

PMID- 27024487
TI  - Is it true that moderate alcohol consumption can be somewhat beneficial to women
      who have rheumatoid arthritis?

PMID- 27024489
TI  - I feel as if I'm in a constant state of "agida" and have difficulty sleeping at
      night.  Because of the lack of sleep, I'm irritable the next day.  This has been
      going on for months.  What could be the problem?

PMID- 27024488
TI  - Why has the Federal Drug Administration (FDA) issued new guidelines for the sleep
      aid drug zolpidem?

PMID- 27024490
TI  - I eat a diet lower in cholesterol than my husband, but my LDL ("bad") cholesterol
      is higher. Why is this? How much does the cholesterol in your diet affect the
      cholesterol levels in the blood?

PMID- 27024491
TI  - Learn how to sleep again.  The crucial step is addressing physical ailments,
      behaviors, and attitudes that disturb slumber.

PMID- 27024492
TI  - Are your whole grains wholly healthy?

PMID- 27024493
TI  - Is acupuncture for you?  The latest research says this traditional Chinese
      healing practice is worth a try for chronic pain.

PMID- 27024494
TI  - On call.  I know lots of people who have had shingles, and I hear there is a
      vaccination to prevent this condition.  Dies it work? Is it safe?

PMID- 27024496
TI  - When a depression drug fails, add talk therapy.

PMID- 27024495
TI  - On call. I am taking simvastatin for high cholesterol. Should I take coenzyme Q
      10 to prevent muscle pain?

PMID- 27024497
TI  - Hepatitis C treatment extends life.

PMID- 27024499
TI  - New ways to beat osteoarthritis pain. Just over the horizon, therapies are being
      developed to relieve osteoarthritis. But there's a lot you can do to feel better
      today.

PMID- 27024498
TI  - No generation gap found in diabetes education.

PMID- 27024500
TI  - Ask the doctor.  I have bleeding hemorrhoids, and my doctor recommends surgery. 
      How do I know if this is really necessary?

PMID- 27024501
TI  - Ask the doctor.  My top blood pressure number is high, and my bottom number is
      normal.  Can a healthier lifestyle lower my blood pressure?

PMID- 27024502
TI  - Avoiding dangerous drug interactions.  How to make sure the medicines you're
      taking are safe for you.

PMID- 27024503
TI  - What can you do about incontinence.  Getting past the embarrassment is the first
      step in treating involuntary urine leakage.

PMID- 27024504
TI  - Why the Mediterranean diet is so good for your heart.  Easy steps to help you
      make the switch to this heart-healthy eating plan.

PMID- 27024505
TI  - Calcium could harm women's hearts.

PMID- 27024506
TI  - Older women can wait two years for next mammogram.

PMID- 27024507
TI  - Mindfulness mediation for arthritis.

PMID- 27024508
TI  - Tai chi prevents falls after a stroke.

PMID- 27024509
TI  - Reducing stress works better than supplements for heart disease. Mind-body
      medicine lowers your cardiac risk, and getting nutrients from food sources is
      better than taking a pill.

PMID- 27024510
TI  - Caffeine may worsen urinary leakage.

PMID- 27024511
TI  - On call. Recently, my insurance company switched my cholesterol medication from
      Lipitor to generic atorvastatin. Are generic medication as good as brand-name
      drugs?

PMID- 27024512
TI  - On call I had a heart attack about five years ago, but I have no symptoms now. I
      am planning a vacation where I will be spending several days over 8,000 feet. Do
      I need to take any precautions?

PMID- 27024513
TI  - Get your heart pumping in the fight against forgetfulness.  Regular exercise
      releases brain chemicals that support better memory, concentration, and mental
      sharpness.

PMID- 27024514
TI  - Weak kidneys? Pay attention but don't worry excessively.  Many older men have low
      normal kidney function, but it doesn't need to become a serious health threat.

PMID- 27024515
TI  - Free preventive services for men.  Healthcare reform lowers the cost of checking
      for hidden diseases and conditions, but make sure you really need these tests.

PMID- 27024517
TI  - Irregular heart rhythm linked to mental decline.

PMID- 27024516
TI  - Osteoporosis update for men.  Do you need to be concerned about age-related bone
      loss?  Yes--but not as much as women do.

PMID- 27024518
TI  - Have osteoarthritis? Careful with narcotic painkillers.

PMID- 27024519
TI  - Mediterranean diet reduces risk of heart attacks.

PMID- 27024520
TI  - New hope for Alzheimer's.  Alzheimer's research shifts direction, creating
      potential new therapeutic avenues for people at risk.

PMID- 27024521
TI  - Other colon cancer tests may be good alternatives to repeat colonoscopy.

PMID- 27024522
TI  - Ask the doctor.  My cholesterol is normal, but my triglyceride level is high. 
      Should I be concerned?

PMID- 27024523
TI  - Ask the doctor. I have pain in the ball of my foot, which my doctor thinks is
      caused by a Morton's neuroma. How did I get this and what can I do about it?

PMID- 27024524
TI  - Sex and your heart.  Heart disease doesn't have to bring your love life to a
      halt.

PMID- 27024526
TI  - Do you need to see your gynecologist every year?  Recommendations no longer
      support annual visits--but every woman is different.

PMID- 27024525
TI  - Common vision problems in women.  Don't ignore vision problems--get them
      diagnosed and treated now, so you can preserve your sight.

PMID- 27024527
TI  - Digital tablets make reading easier.

PMID- 27024528
TI  - Quit smoking and live longer.

PMID- 27024529
TI  - Breast cancer drugs linked to heart failure in older women.

PMID- 27024530
TI  - Considering a gluten-free diet.  It's not just for people with celiac disease. 
      But is it for you?

PMID- 27024531
TI  - Ask the doctor. I've been diagnosed with shingles. Is there anything I can take
      for the pain?

PMID- 27024533
TI  - Physical vs. mental activity.  Which is better to keep your brain fit?

PMID- 27024532
TI  - Ask the doctor.  I've heard that age-related macular degeneration is a common
      cause of blindness.  Do copper, zinc, or lutein help prevent it?

PMID- 27024534
TI  - Bypass better than stenting for diabetics? The surgery can be a better option for
      some with this condition.

PMID- 27024535
TI  - Arthroscopic shoulder surgery.  When the minimally invasive procedure is
      warranted.

PMID- 27024537
TI  - Prevent peripheral artery disease. Eliminating four risk factors can reduce PAD
      cases.

PMID- 27024536
TI  - Watch out for the "salty six'.  Quick tips when trying to cut sodium intake.

PMID- 27024538
TI  - New pill better targets rheumatoid arthritis.  It's the first oral therapy
      approved for RA in more than 15 years.

PMID- 27024540
TI  - Are painkillers also killing your hearing?  Frequent use may be a preventable
      contributor to hearing loss.

PMID- 27024539
TI  - Stop leg wounds that don't heal.  The easy fix that millions of people may be
      ignoring.

PMID- 27024541
TI  - What you should know about: magnesium.

PMID- 27024543
TI  - Smartphone application not always reliable to assess skin cancer.

PMID- 27024542
TI  - New thinking on migraine triggers.

PMID- 27024544
TI  - Sugary beverages raise diabetes risk: coffee and tea don't.

PMID- 27024545
TI  - Hearing loss may be related to cognitive decline.

PMID- 27024546
TI  - Dealing with a diagnosis of early-stage dementia.

PMID- 27024547
TI  - Relief for everyday constipation: the inside tract.

PMID- 27024548
TI  - The best ways to manage stable heart disease. Updating standard advice with
      modern therapies.

PMID- 27024549
TI  - Fighting infection with your fork.

PMID- 27024550
TI  - Raynaud's: coping with a medical phenomenon.

PMID- 27024551
TI  - Self-help strategies for managing lymphedema.

PMID- 27024553
TI  - Is it safe to split my pills?

PMID- 27024552
TI  - My doctor says my body mass index (BMI) classifies me as obese.  I knew I was
      overweight but not obese.  What's happening and what can I do?

PMID- 27024555
TI  - Tennis elbow shot doesn't score.

PMID- 27024554
TI  - Regaining bladder control.

PMID- 27024556
TI  - Is your salad making you sick?

PMID- 27024557
TI  - Linking high blood pressure and hip fracture.

PMID- 27024558
TI  - Tests your doctor may order to determine whether you have heart disease.  These
      noninvasive tests also help assess the risk of heart attack.  Positive results
      may require further testing or an invasive procedure.

PMID- 27024559
TI  - What it means when your doctor says . . ."you have atrial fibrillation".

PMID- 27024560
TI  - Ask the doctors. I have a heart murmur that my doctor says is caused by a leaky
      mitral valve. I feel perfectly fine, am an active gardener, and enjoy playing
      with my grandchildren. My last echocardiogram showed that my heart is getting
      bigger, and my doctor says it is time to operate on the valve. Isn't this
      suggestion a bit drastic?

PMID- 27024561
TI  - Ask the doctors. I have coronary artery disease, and my primary care doctor just
      told me that changes in my tests indicate I have prediabetes. This doesn't sound
      like a big deal, since I don't need medicines yet. But I'm wondering if I should
      start doing anything differently?

PMID- 27024562
TI  - Watch your weight and your waist: extra pounds may mean heart disease.  When the
      scale starts creeping up, here's what you should do, and why.  Beware: belly fat
      is particularly dangerous.

PMID- 27024563
TI  - Managing your blood thinners.  Avoid these common mistakes to prevent serious
      problems.

PMID- 27024564
TI  - Rx for heart failure: coffee.

PMID- 27024567
TI  - How CPR has changed.

PMID- 27024566
TI  - Free app predicts risk of heart attack.

PMID- 27024565
TI  - Antidepressants and arrhythmias.

PMID- 27024568
TI  - Avoid back pain and improve balance by strengthening core muscles.  You don't
      have to do crunches; these simple, gentle exercises will make a big difference.

PMID- 27024569
TI  - Ask the doctor.  I have had restless leg syndrome for years.  Is there anything I
      can take for it that won't cause side effects?

PMID- 27024570
TI  - Ask the doctor.  I hear that it's now been proved that the Mediterranean diet
      really is good for your heart.  Is that true?

PMID- 27024571
TI  - Migraines: can dementia, stroke or heart attack be next? New Harvard research
      confirms some links, rejects others.

PMID- 27024572
TI  - Implantable defibrillators: simple fix may save lives. Raising the allowable
      beats per minute may avoid injury, even death, from inappropriate shocks.

PMID- 27024573
TI  - Some computer downloads for better health should be avoided.  Approach these
      phone, tablet, or computer programs with caution if they make big promises.

PMID- 27024574
TI  - Easy way to stop knee arthritis from progressing.  There's a lot you can do, but
      Harvard researchers now say skipping your daily soda may also help.

PMID- 27024575
TI  - Caution: cancer risk elevated in women with dense breasts.

PMID- 27024576
TI  - Dodging skin irritations from problem plants.  These simple steps can save you
      from itchy, oozing rashes.

PMID- 27024577
TI  - What you need to know about: inhalers.

PMID- 27024578
TI  - Harvard study says yes to eggs.

PMID- 27024579
TI  - Taking charge of your health.  Top 5 tips to help you become proactive in your
      health care.

PMID- 27024580
TI  - Ask the doctor.  I feel tired all the time.  How do you know if it's a sign of
      something serious?

PMID- 27024581
TI  - Ask the doctor.  My doctor told me to cut out fats to lower my heart disease
      risk.  What's the best way to do that?

PMID- 27024582
TI  - How to cope with drug-resistant hypertension. You still have options when your
      blood pressure can't be controlled.

PMID- 27024583
TI  - Cognitive behavioral therapy helps depression.  Research shows the approach is
      especially helpful for those who aren't aided by drugs.

PMID- 27024584
TI  - Avoiding knee or hip surgery.  Losing weight, strengthening muscles, and
      increasing flexibility may help you stave off joint replacement.

PMID- 27024586
TI  - Specks in your vision can signal serious eye conditions.  These "floaters" are
      not just bothersome.  They can be signs of potential retinal disease.

PMID- 27024585
TI  - Silent urinary infections, serious consequences.  Why it's vital to know the
      causes and symptoms of urinary tract infections and how to treat and prevent
      them.

PMID- 27024587
TI  - What to look for in sunscreen: understanding the new rules for sunscreen labels.

PMID- 27024588
TI  - What you need to know about:  calcium supplements.  Calcium is most effective
      when it comes from the food you eat.  Use our guide to identify convenient
      sources.

PMID- 27024589
TI  - Best way to prevent advanced colon cancer.

PMID- 27024590
TI  - Harvard study: benefits of quitting smoking trump subsequent weight gain.

PMID- 27024591
TI  - Aspirin linked to preventing deadly skin cancer.

PMID- 27024592
TI  - Brain scan shows best time to treat plaque.

PMID- 27024593
TI  - Inflammation linked to vision loss.

PMID- 27024594
TI  - Earlier detection of ovarian/endometrial cancers.  Two pioneering technologies
      involving molecular approaches are under study.

PMID- 27024595
TI  - Cardiovascular risk tests predict likelihood of mental decline.  Framingham
      scoring systems prove useful in identifying middle-aged adults most likely to
      experience cognitive decline later in life.

PMID- 27024596
TI  - Minimally invasive surgery for chronic low back pain.  When conservative
      treatment fails, new options include MIS spine fusion, microdiscectomy, and
      microlaminectomy to relieve pain and restore function.

PMID- 27024597
TI  - How gastric bypass surgery relieves diabetes symptoms. The procedure alters
      hormones and amino acids involved with digestion.

PMID- 27024598
TI  - Mediterranean diet may preserve cognitive skills.  More evidence that a healthy
      diet contributes to preserving cognition as we age.

PMID- 27024599
TI  - I've had arthritis in my feet and hands for years, but now my doctor is telling
      me that the pain I feel in my ribs is arthritis in my chest.  Can this be?

PMID- 27024600
TI  - I know that grapefruit interacts with some heart medications, but are there other
      food-medication interactions I should be aware of?

PMID- 27024601
TI  - What can you tell me about levodopa, the drug used to treat Parkinson's disease?

PMID- 27024602
TI  - Your guide to managing multiple ailments.

PMID- 27024604
TI  - Shouldering a burden: dislocations can lead to long-term problems.

PMID- 27024603
TI  - Bell's palsy: the best path to full recovery.

PMID- 27024605
TI  - Your yearly gyn exam--do you still need it?

PMID- 27024606
TI  - What can I do about treating chronic hoarseness?

PMID- 27024607
TI  - For some weeks I've had a painful swelling behind my left knee that I've been
      told is a Baker's cyst.  Does this condition require surgery?

PMID- 27024609
TI  - Stroke and hip replacement.

PMID- 27024608
TI  - Benzodiazepines may raise dementia risk.

PMID- 27024610
TI  - Giving your health a lift.

PMID- 27024611
TI  - A superior MS drug on the horizon.

PMID- 27024612
TI  - Steroid injections for back pain: worth the risks?

PMID- 27024613
TI  - Antibiotics do's and don'ts.

PMID- 27024614
TI  - Talking about end-of-life care with your doctor.  Act sooner, not later, while
      you're well enough to make the best choices.

PMID- 27024615
TI  - White-coat hypertension--should you be treated?

PMID- 27024616
TI  - Often overlooked: diabetes pain.

PMID- 27024617
TI  - I'm lactose intolerant.  Are there any dairy products that won't make me feel
      sick?

PMID- 27024618
TI  - Does the recirculated air on planes increase the risk of catching a virus?

PMID- 27024619
TI  - COPD: another stroke risk factor.

PMID- 27024620
TI  - Ultrasound approved for screening dense breasts.

PMID- 27024621
TI  - New oral therapy for RA.

PMID- 27024622
TI  - Protecting against vascular dementia with exercise.

PMID- 27024623
TI  - Don't let hot weather take your breath away.  Study: summer heat can pose a risk
      to people with respiratory illnesses.

PMID- 27024624
TI  - Nonalcoholic fatty liver disease: are you at risk?

PMID- 27024625
TI  - Post-traumatic stress disorder. PTSD doesn't just affect war veterans--it can be
      triggered by critical illness, too.

PMID- 27024626
TI  - A pain in the neck: what you should know about whiplash.

PMID- 27024627
TI  - Book vs. e-reader: which is best for older eyes?

PMID- 27024628
TI  - When sex is painful: a new remedy for women.

PMID- 27024629
TI  - I have a wart on my hand.  Does it need to be treated?

PMID- 27024630
TI  - I think I have hemorrhoids.  How can I get rid of them?

PMID- 27024631
TI  - Azithromycin linked to irregular heartbeat.

PMID- 27024632
TI  - Putting out the fire ant's sting.

PMID- 27024633
TI  - Patching up migraines.

PMID- 27024634
TI  - Foot patrol: protect your feet if you have diabetes.

PMID- 27024635
TI  - Taking a closer look at niacin's effects on heart health.  Studies question the
      usefulness of raising HDL cholesterol with niacin.

PMID- 27024636
TI  - Fending off gout attacks.  New guidelines emphasize ongoing drug therapy over
      dietary restrictions.

PMID- 27024637
TI  - When you don't get enough sleep.  The risks you face from sleep deprivation.

PMID- 27024638
TI  - There's no place like home for hemodialysis.

PMID- 27024639
TI  - I've begun to experience blurry vision.  Although I haven't had vision problems
      in the past, I do have arthritis.  Could my medications be causing this?

PMID- 27024641
TI  - Cross at the green, not in between.

PMID- 27024640
TI  - My doctor told me the swelling in my ankles was edema.  What causes edema?  Can I
      prevent it?

PMID- 27024642
TI  - Some symptoms in early-stage Parkinson's often undertreated.

PMID- 27024643
TI  - Heartburn, belly fat and cigarettes:  a recipe for cancer.

PMID- 27024644
TI  - Hearing loss tied to memory loss.

PMID- 27024645
TI  - Better memory: use these simple tricks to help you remember.  These proven
      strategies will help you lock onto names and faces and stop forgetting where you
      put your keys and wallet.

PMID- 27024646
TI  - On call.  I have noticed that my sense of taste has weakened with aging.  Is this
      normal?

PMID- 27024648
TI  - Daily moves to prevent low back pain.  Stretching and strengthening daily is your
      best bet to delay the next attack of low back pain.

PMID- 27024647
TI  - I drink five or six cups of caffeinated coffee daily.  Are there any known health
      risks to drinking a lot of coffee?  Should I cut back?

PMID- 27024649
TI  - The pros and cons of statins.  Cholesterol-lowering statin drugs won't make you
      heart attack-proof, but they do reduce your risk.

PMID- 27024650
TI  - They found colon polyps: now what? Follow-up exams at the right time are
      essential to prevent cancer from developing.

PMID- 27024651
TI  - How to choose a healthy yogurt. Look for low-fat varieties without added
      sweeteners. Stir in your own ingredients to build the perfect breakfast.

PMID- 27024652
TI  - Pain beyond the prostate.  Consider alternative therapies for chronic pelvic
      pain.

PMID- 27024654
TI  - Emergency room visits involving popular sleep drug rise sharply.

PMID- 27024653
TI  - Sodium remains high in processed and restaurant foods.

PMID- 27024655
TI  - Urologists update PSA guideline.

PMID- 27024656
TI  - The right shoes:  the key to better health.  Your mobility and independence begin
      with your feet.  Finding footwear that fits can keep you moving.

PMID- 27024657
TI  - Ask the doctor. I am taking pravastatin for high cholesterol, but my numbers are
      still high. Should I try red yeast rice?

PMID- 27024659
TI  - A heart condition may foreshadow dementia, even without a stroke. New studies
      show resolving heart problems now may preserve brain function later.

PMID- 27024658
TI  - Ask the doctor.  Since I went through menopause, sex has become very painful.  I
      no longer enjoy it.  Are there any treatments I can try?

PMID- 27024660
TI  - Don't give up on losing weight and staying fit.  Postmenopausal weight gain and
      loss of muscle tone aren't inevitable--you just need to work a little harder.

PMID- 27024661
TI  - Vaccinations: myth vs. reality.  Don't let misinformation prevent you from
      getting the protection you need.

PMID- 27024662
TI  - Varicose veins: searching for less-invasive treatments. These twisted, ropy veins
      are more than unsightly. They can cause real discomfort if you don't treat them.

PMID- 27024663
TI  - Real-time digital mammograms more accurate than computed radiography.

PMID- 27024664
TI  - Two osteoporosis drugs better than one.

PMID- 27024666
TI  - New guidelines recommend CT screening for long-term smokers.

PMID- 27024665
TI  - Pelvic organ prolapse surgery less effective over time.

PMID- 27024667
TI  - Expanding HIV care and training into Arkansas CHCs.

PMID- 27024668
TI  - Identifying barriers to hepatitis C treatment in co-infected patients at a New
      Orleans clinic.

PMID- 27024669
TI  - What patients and providers need to know about HIV/AIDS and life insurance.

PMID- 27024670
TI  - HOP participates in identifying foodborne illness knowledge gaps.

PMID- 27024671
TI  - Maintaining independence: don't overlook foot and ankle health.  To stay moving
      you need to get moving.  Follow these top five strategies to be more active.

PMID- 27024673
TI  - Ask the doctor. I'm more forgetful that I used to be.  I'm not worried about
      dementia, but are there tricks for improving my memory?

PMID- 27024672
TI  - Ask the doctor.  Where do you stand on glucosamine and chondroitin?  Do you think
      they're helpful or just hype?

PMID- 27024674
TI  - Exercise is an all-natural treatment to fight depression.  Exercise is as
      effective as drugs in some cases.

PMID- 27024675
TI  - Mediation offers significant heart benefits.

PMID- 27024677
TI  - Overcoming an overactive bladder. Get your life back if you're experiencing this
      easily treatable condition.

PMID- 27024676
TI  - Rethinking fiber and hydration can lead to better colon health. They're the
      biggest contributors to improved digestion.

PMID- 27024678
TI  - Top foods to help protect your vision.  You'll want to concentrate on yellow and
      orange fruits and vegetables, plus egg yolks and fatty, cold-water fish.

PMID- 27024679
TI  - Tips to help prevent and treat rosacea.

PMID- 27024680
TI  - What you need to know about: diuretics.

PMID- 27024681
TI  - Fish oil supplements ineffective for heart health?

PMID- 27024682
TI  - Avoid a potential trigger for Parkinson's disease.

PMID- 27024683
TI  - New findings about preserving physical function and mobility.

PMID- 27024684
TI  - Stay driving to stay independent. Consider these health issues to keep you safe
      on the road.

PMID- 27024685
TI  - Ask the doctor.  I'm 73 and in great health.  Is it okay to skip my annual
      physical?

PMID- 27024686
TI  - Ask the doctor.  Does secondhand smoke increase my cancer risk?  I've heard
      conflicting information.

PMID- 27024687
TI  - Are you short of breath?  It may be a simple case of asthma or a serious heart
      condition.  Here's when to report it.

PMID- 27024688
TI  - Fall vaccination roundup.  A flu shot may not be enough; you may be ready for
      other vaccinations.

PMID- 27024689
TI  - The importance of stretching.  It's not enough to build muscle and achieve
      aerobic fitness.  You need to think about flexibility, too.

PMID- 27024690
TI  - Improve sleep by eating right.  Why caffeine, spicy foods, and alcohol make poor
      bedfellows.

PMID- 27024691
TI  - Meat lover's guide to healthy eating.  If you're going to eat red meat, make sure
      it's lean and that portions are small.

PMID- 27024692
TI  - The magic of mindfulness.  Simple, life-changing steps to get engaged and get
      healthy.

PMID- 27024694
TI  - Don't ignore stroke-like symptoms.

PMID- 27024693
TI  - What you should know about: generic vs. brand-name statins.

PMID- 27024695
TI  - Older people experience eating disorders, too.

PMID- 27024697
TI  - 6 numbers you absolutely need to know. To keep your heart disease risks in check,
      stay on top of these key health indicators.

PMID- 27024696
TI  - Low blood sugar and dementia: avoiding the downward spiral.

PMID- 27024698
TI  - Ask the doctor.  I've been very unstable on my feet lately. Can tai chi help
      improve my balance?

PMID- 27024699
TI  - Ask the doctor.  Sometimes I leak a small amount of feces without noticing it. 
      It just appears in my pants.  What can I do about this?

PMID- 27024701
TI  - Important nutrients you could be missing. How to identify--and treat--a
      nutritional deficiency before it endangers your health.

PMID- 27024700
TI  - Pain relief:  taking NSAIDs safely.  Before you use these popular pain pills,
      weigh the heart risks and other side effects carefully.

PMID- 27024702
TI  - What is your heart risk score?

PMID- 27024703
TI  - Irregular heartbeat linked to earlier mental decline.

PMID- 27024704
TI  - COPD rates rise in women.

PMID- 27024705
TI  - New guidelines released for managing knee arthritis.

PMID- 27024706
TI  - Lack of sleep harmful to women's hearts.

PMID- 27024707
TI  - "Low salt" still the dietary rule.  Even though there are reports of possible
      danger from extremely low sodium intake, Harvard experts agree: less salt is
      better.

PMID- 27024708
TI  - Ask the doctors. I've been taking Coumadin for some time and have begun taking
      Plavix after having had several stents put in to open blocked arteries. My doctor
      said Plavix would prevent clots. Isn't that what Coumadin does?

PMID- 27024709
TI  - Ask the doctors.  I am a 78-year-old woman and have atrial fibrillation.  My
      physician prescribed me Coumadin.  Last month aspirin was added to my regimen. 
      Is it okay to take both of these drugs together?

PMID- 27024710
TI  - Ask the doctors.  So many times I have read that people with a BMI greater than
      25 are overweight.  I'm a man 5 feet, 5 inches tall weighing 168 pounds.  My BMI
      is 28.  I have a flat stomach.  I lift weights and do push-ups and pull-ups. 
      Does the BMI mislead body builders and athletes by saying we are overweight?

PMID- 27024712
TI  - Shortness of breath: a common reason for calling the doctor.  Know when
      difficulty breathing is an emergency.

PMID- 27024711
TI  - How to lower your stroke risk.  You can do more than you think to avoid a fatal
      or debilitating "brain attack".

PMID- 27024713
TI  - Too much sitting linked to heart attack and stroke--even if active. Don't spend
      workdays in your chair and evenings on the couch, even if you exercise every day.

PMID- 27024714
TI  - What's more important than your life span?  Your health span.  You are never too
      old to add heart-healthy years to your life.

PMID- 27024715
TI  - Don't stop taking a medication if you experience an unpleasant reaction.  Talk to
      your doctor first.  The benefits of the drug may far outweigh any side effects.

PMID- 27024716
TI  - Dietary vitamin E and heart failure.

PMID- 27024717
TI  - Thick air, thick arteries.

PMID- 27024718
TI  - Stroke: every minute counts.

PMID- 27024719
TI  - Stop worry about fat. When making choices about what food to eat, keep your eye
      on the big picture. Favor healthy fats instead of avoiding all fats.

PMID- 27024721
TI  - On call.  As I get older, my voice sounds raspier.  Is this normal? Is there
      anything I can do to reverse these changes?

PMID- 27024720
TI  - On call.  At a recent check-up, my doctor told me that my cholesterol was normal
      but my triglycerides were high.  What are triglycerides, and do I need to lower
      them?

PMID- 27024722
TI  - Flu shot:  good insurance, not a guarantee.  Not everyone will be protected by
      the flu shot, but it's still a good idea for men at risk of complications from
      influenza.

PMID- 27024724
TI  - How to sleep better with chronic pain. Rely on your natural sleep rhythms as much
      as possible instead of sleep medications and painkillers.

PMID- 27024723
TI  - Relief from intestinal gas.  To identify troublesome foods, keep a detailed daily
      record of everything you eat.

PMID- 27024725
TI  - Dry eyes?  Finding the right lubricating drops is essential.  Get an exam to
      pinpoint the cause and then choose.

PMID- 27024726
TI  - Counting steps kick-starts health.

PMID- 27024728
TI  - Fast food packs unexpected calories.

PMID- 27024727
TI  - Statins linked to muscle injuries.

PMID- 27024729
TI  - Prostate biopsy side effects are common.

PMID- 27024730
TI  - Prevention.  New guidelines released for occupational exposure.

PMID- 27024731
TI  - Treatment.  Peer intervention, pharmacists can have impact on testing, treatment.

PMID- 27024732
TI  - Homeless women at greater STI risk due to social network.

PMID- 27024733
TI  - Offenders more likely to contract STIs after release.

PMID- 27024734
TI  - Study looks at lack of follow-up.

PMID- 27024735
TI  - Insurance.  Court finds discontinuance of disability benefits capricious.

PMID- 27024736
TI  - Prisons.  Inmate fails to state claim under AIDS Confidentiality Act.

PMID- 27024737
TI  - SSI.  Woman's testimony did not match with physicians' records.

PMID- 27024738
TI  - ADA.  Question of whether man was terminated for HIV remains.

PMID- 27024739
TI  - Balancing bleeding vs. stroke risk when you have atrial fibrillation. Careful
      compliance makes management of anticoagulant and antiplatelet drugs safer.

PMID- 27024740
TI  - Ask the doctors.  I used to see a cardiologist for mild high blood pressure, and
      she performed a cardiac ultrasound, electrocardiogram, and stress test with
      nuclear imaging every year.  I felt reassured when my test results were normal. 
      I had to switch to a new cardiologist, and he routinely does an
      electrocardiogram, but no other tests.  He says I'm doing fine, and that I don't
      need those tests every year.  Am I being neglected?  I am not getting as much
      attention as I used to?

PMID- 27024741
TI  - Ask the doctors.  A friend with heart disease was doing fine until he underwent
      an operation for colon cancer.  He got through the first few days without any
      problems, but then had a heart attack on the fourth day and nearly died.  Why
      would he have had a heart attack after an operation?  I need to have surgery and
      am wondering how dangerous it will be.

PMID- 27024742
TI  - Eat blueberries and strawberries three times per week.  A significant study links
      berry consumption with improved heart health.  You can't get the same benefit
      from a pill or supplement.

PMID- 27024743
TI  - Bypass or angioplasty with stenting:  how do you choose?  It's your doctor's
      call, but it's good to understand, and to weigh, your options.

PMID- 27024744
TI  - Sleep problems may increase the risk of heart attack and stroke.  If you toss and
      turn at night or rattle the windows with your snores, you may be headed for heart
      trouble.

PMID- 27024745
TI  - Best medicine: the science of exercise shows the benefits beyond weight loss. 
      Staying active resets your body's biochemical balance.  Key point: go easy, but
      go consistently.

PMID- 27024747
TI  - Advice from the doctor...what you can do to lower your bleeding risk.

PMID- 27024746
TI  - More evidence red meat may be bad for your heart. A new study suggests frequent
      meat eaters should cut back on red meat--and should avoid L-carnitine
      supplements.

PMID- 27024748
TI  - Old hearts made young by natural substance.

PMID- 27024750
TI  - Living better with heart failure.  Revised clinical guidelines update treatment
      strategies.

PMID- 27024749
TI  - Had problems with statins? Try them again.

PMID- 27024751
TI  - Eating out: beware of 'healthy' menus.

PMID- 27024753
TI  - Pneumonia's long-term health consequences.

PMID- 27024752
TI  - Vision quest: safeguarding your eyesight.

PMID- 27024754
TI  - Tests for acute low back pain: necessary or not?

PMID- 27024755
TI  - If my doctor's office doesn't call with my test results, can I assume that
      everything is normal?

PMID- 27024756
TI  - I have what looks like a cyst on my wrist.  Should I be concerned?

PMID- 27024757
TI  - Spreading germs with bad habits.

PMID- 27024759
TI  - The war on prostate cancer.

PMID- 27024758
TI  - Embarrassing itching explained.

PMID- 27024760
TI  - When antibiotics and statins don't mix.

PMID- 27024761
TI  - Make these better food choices for better heart health. Simple substitutions
      yield big health dividends.

PMID- 27024762
TI  - Ask the doctor.  My legs hurt if I walk too much, especially going uphill or
      taking several flights of stairs.  My internist told me that it was probably poor
      circulation.  How can I be sure--and is there anything I can do about it?

PMID- 27024763
TI  - Ask the doctor.  I had been checking my blood pressure regularly for several
      years and it has never been high.  But now multiple checks by my doctor have
      shown that my blood pressure is high.  Why could that be?

PMID- 27024764
TI  - Prevent kidney disease to prevent heart disease.  Protect your heart by
      protecting your kidneys.  Here's how.

PMID- 27024765
TI  - When to seek genetic testing for heart disease.  If genetic heart disease strikes
      a family, testing offers options.

PMID- 27024766
TI  - Tell your dentist about your heart problems.  Some people with heart valve
      disease need special dental care.

PMID- 27024768
TI  - Eat breakfast to lower heart risk.

PMID- 27024767
TI  - Hypertropic cardiomyopathy: what you can do.  Early diagnosis can prevent sudden
      deaths.

PMID- 27024769
TI  - Belly fat linked to heart disease and cancer.

PMID- 27024770
TI  - Protecting heart cells after heart attack.

PMID- 27024771
TI  - Before dementia begins:  what helps?  Diet, exercise, and appropriate medical
      care can slow the decline in memory and mental skills.

PMID- 27024772
TI  - On call.  Is it true that in some people, low-dose aspirin doesn't help to
      prevent heart attacks?  Should I take a higher dose to make sure it works?

PMID- 27024773
TI  - On call.  Doctors always say to get checked out if you have a persistent cough. 
      But how long would a cough have to last before I should see a doctor?

PMID- 27024774
TI  - Arthritic knees: exercise can help, but don't overdo it.  Appropriate exercise
      reduces pain and stiffness and improves the ability to function.

PMID- 27024775
TI  - Blocked arteries may be causing that leg pain when you walk.  Regular exercise
      helps you walk farther with less discomfort.

PMID- 27024777
TI  - New evidence that a heart-healthy diet also helps fight prostate cancer. Replace
      refined carbs with vegetable fats to slow early stage cancer from progressing to
      a more lethal form.

PMID- 27024776
TI  - How to prevent kidney stones. Drink water and cut back on sodium and animal
      protein to avoid kidney stones or to keep them from coming back.

PMID- 27024778
TI  - Dietary supplements: no magic bullets.

PMID- 27024780
TI  - Panel backs HCV test for baby boomers.

PMID- 27024779
TI  - Online Alzheimer's tests get "F" from experts.

PMID- 27024781
TI  - Act quickly to stop stroke damage.

PMID- 27024782
TI  - Try these techniques to relieve common urinary symptoms without medication.  For
      nighttime urination, frequency, or urgency, these methods really work.  And you
      can always switch to medication later.

PMID- 27024783
TI  - On call.  Which is best for pain and stiffness from a sore back--heat or cold?

PMID- 27024784
TI  - On call.  I've started to notice a slight shakiness in my writing hand.  Is this
      just normal aging or should I get it checked out?

PMID- 27024785
TI  - Heart failure prevention essentials: take these steps. Exercise, healthy eating,
      and appropriate treatment will protect the heart's pumping power.

PMID- 27024786
TI  - That pain in your side could be diverticular disease. Fiber and an active
      lifestyle prevent flare-ups, but act promptly if it hurts or bleeds.

PMID- 27024787
TI  - Computer-based brain training could help keep your mental tools sharp. But only
      if the training isn't boring to you and pushes your limits enough to produce real
      improvement.

PMID- 27024788
TI  - How to build a better sandwich.  Pay attention to portion sizes and sodium
      content, and explore healthier alternatives.

PMID- 27024790
TI  - Is dementia becoming less common?

PMID- 27024789
TI  - Study reveals risk of heavy coffee drinking in those younger than 55.

PMID- 27024791
TI  - Measure blood pressure at home for better control.

PMID- 27024792
TI  - Lung cancer screening now recommended for those at high risk.

PMID- 27024793
TI  - What you need to ask before getting an imaging test.  Know why the test is being
      done, and how it will guide your treatment.

PMID- 27024794
TI  - Ask the doctor. I have osteoporosis, and my doctor has recommended that I take a
      bisphosphonate drug. Is there anything else I can do to protect my bones and keep
      them strong?

PMID- 27024796
TI  - Omega-3-rich food:  good for your heart. Learn what these essential fatty acids
      can do for your cardiovascular health, and where to find the best sources.

PMID- 27024795
TI  - Ask the doctor. My toenails are thick and discolored.  They're so unsightly that
      I'm too embarrassed to wear sandals when I go on vacation.  What can I do about
      them?

PMID- 27024797
TI  - How using computers can help keep your mind sharp.  Surfing the Internet and
      catching up with family and friends online will keep you socially connected, and
      it might improve your memory, too.

PMID- 27024798
TI  - Preventing the burn of heartburn. Follow these anti-reflux strategies to avoid a
      painful end to your holiday meal.

PMID- 27024799
TI  - Long-term use of some blood pressure medicines is linked to breast cancer risk.

PMID- 27024801
TI  - Back pain treatment doesn't follow recommendations.

PMID- 27024800
TI  - Women may not be getting optimal stroke treatment.

PMID- 27024802
TI  - High blood sugar linked to mental decline.

PMID- 27024803
TI  - Treat depression, help the heart.  Learn the warning signs: depression is often
      unrecognized in people with heart disease.

PMID- 27024804
TI  - Ask the doctor.  Every year my doctor used to put me on a treadmill for a stress
      test.  Now he doesn't.  Why?

PMID- 27024805
TI  - Ask the doctor.  I was told I have high blood pressure.  The top number ranges
      from 135 to 145.  I don't want to take medications.  What choices do I have?

PMID- 27024806
TI  - Living with AFib.  Treatment options to improve life with atrial fibrillation.

PMID- 27024807
TI  - Exercise: 15 minutes a day ups lifespan by 3 years.  Exercise: a prescription for
      making your heart stronger.

PMID- 27024808
TI  - Get started: medication management for CAD.  Use simple tools to manage heart
      pills.

PMID- 27024809
TI  - Get a heart monitor.  Serious about exercise? Get a heart monitor.

PMID- 27024810
TI  - Emotional stress induced ischemia.  Reduce emotional stress to avoid heart
      attack.

PMID- 27024811
TI  - No heart risk--or benefit--from diabetes drug Onglyza.

PMID- 27024812
TI  - Longer life after heart attack.

PMID- 27024813
TI  - Arsenic and heart disease.

PMID- 27024814
TI  - Remission. Child treated hours after birth still HIV-negative.

PMID- 27024816
TI  - Treatment.  Study said more can be done for HIV-positive N.Y. inmates.

PMID- 27024815
TI  - Prevention.  Pre-test counseling does not affect risky behaviors, neither does
      PrEP.

PMID- 27024817
TI  - Prisons.  Settlement reached over HIV-positive inmate segregation.

PMID- 27024818
TI  - SSI.  ALJ suspected that man with HIV exaggerated his limitations.

PMID- 27024819
TI  - Privacy.  Patient may proceed with HIV-disclosure suit against hospital.

PMID- 27024820
TI  - Prisons.  New medicine distribution did not violate rights of inmate.

PMID- 27024821
TI  - Getting out in front of mild cognitive impairment.  Good habits, simplified
      choices, and memory tools can help you cope.

PMID- 27024822
TI  - Ask the doctor.  Alzheimer's runs in my family.  Will it help to get gene testing
      for this disease?

PMID- 27024823
TI  - Ask the doctor. A friend told me she takes magnesium pills every day. Does this
      improve your health.

PMID- 27024824
TI  - Heart failure diagnosis: tools for positive outcomes.  Don't get scared.  Be
      proactive by improving diet, exercising, and tracking your symptoms.

PMID- 27024825
TI  - Review your home with this anti-falling checklist.  Search all rooms, hallways,
      and floors in your home to lower your risk of falling.

PMID- 27024826
TI  - Quick fixes for your aching feet.  Addressing arch, tendon, and nail pain will
      protect your mobility and independence.

PMID- 27024827
TI  - Must-haves from the produce aisle.  Don't leave the grocery store without fall
      favorites like apples, cranberries, and butternut squash.

PMID- 27024828
TI  - Is that rash shingles?  Cope with the blistering rash using antivirals and
      painkillers.

PMID- 27024830
TI  - Get acclimated before activity in higher altitudes.

PMID- 27024829
TI  - Caution: these are the most addictive pain meds.  97% of users don't have a
      problem with opioids.  Here's how to avoid becoming part of the other 3%.

PMID- 27024831
TI  - Don't look to insoles to solve your knee pain.

PMID- 27024832
TI  - How good are you at putting names and faces together?

PMID- 27024833
TI  - Don't brush off signs of a "brain attack".  Stroke symptoms that go away on their
      own are still a medical emergency.  Get to a hospital as fast as you can.

PMID- 27024834
TI  - On call. Is extra-virgin olive oil more heart-healthy than regular olive oil?

PMID- 27024836
TI  - Men: don't ignore signs of depression.  Anger or aches and pains can hide
      underlying depression.  Seek prompt treatment to protect your heart and mind.

PMID- 27024835
TI  - On call. My doctor has recommended that I have a colonoscopy this year. The last
      time I had one, the preparation I had to drink the day before the procedure
      tasted awful. Are there any new preparations that are easier to take?

PMID- 27024837
TI  - Chronic heartburn: do you need an endoscopy?  Before your doctor takes a "just in
      case" look down your throat for trouble, make sure you really need this
      procedure.

PMID- 27024838
TI  - Make your end-of-life wishes known.  Healthcare proxies and advance directives
      help ensure you get only the kind of care you want.

PMID- 27024839
TI  - New tests promise smarter prostate cancer screening and treatment. Clues from
      genes and other cancer markers can help men make decisions, but come with
      important limitations.

PMID- 27024840
TI  - Diet + exercise = less arthritis pain.

PMID- 27024841
TI  - Virus linked to throat cancer often clears spontaneously.

PMID- 27024842
TI  - Diets for aging brains.

PMID- 27024843
TI  - Study puts hard numbers on cardiovascular risks of NSAIDs.

PMID- 27024844
TI  - How to manage your medicines.  Before you begin taking another prescription, make
      sure all your medications are right for you.

PMID- 27024845
TI  - Ask the doctor.  My husband is always warm, and I'm always cold, no matter what
      the time of year.  Are women just naturally colder than men, or could there be
      something wrong with me?

PMID- 27024846
TI  - Ask the doctor. Is there any medication or over-the-counter supplement or vitamin
      I can take to prevent dementia?

PMID- 27024847
TI  - Stress and your heart.  The real connection between stress and heart disease, and
      what to do if you're under too much pressure.

PMID- 27024848
TI  - Could you have prediabetes?  Millions of women have no idea they're at risk for
      diabetes.  Find out if you're one of them, and take action to prevent this
      disease.

PMID- 27024849
TI  - Insoles for arthritic knees.  Research finds little, if any, benefit to these
      shoe inserts.

PMID- 27024851
TI  - New guidelines for treating vaginal atrophy.

PMID- 27024850
TI  - Best nondairy sources of calcium. How much calcium you need, and where to find it
      outside of the dairy aisle.

PMID- 27024852
TI  - Stents work well in women.

PMID- 27024853
TI  - Short bouts of exercise are enough to manage weight.

PMID- 27024854
TI  - Statins lower heart attack risks in people without heart disease.

PMID- 27024855
TI  - How to stay in your own home longer.  Home health care and private duty care can
      help you maintain your independence in a familiar space.

PMID- 27024856
TI  - Ask the doctor.  Can exercising ward of Alzheimer's disease or dementia?

PMID- 27024857
TI  - Ask the doctor.  I've heard that red wine can prevent heart disease.  Is that an
      old wives' tale?

PMID- 27024858
TI  - Try this to lower your blood pressure.  Monitoring at home controls high blood
      pressure better than infrequent doctor visits.

PMID- 27024859
TI  - Easy fixes for aching shoulders.  Stretching and strengthening your shoulders can
      help you prevent pain and avoid surgery.

PMID- 27024860
TI  - Simple sets to get happier & healthier. Being grateful, doing things for others,
      and improving your health will pay off.

PMID- 27024861
TI  - Could those common symptoms be thyroid trouble? Fatigue, brain fog, and weight
      gain are telltale signs that may be mistaken for other conditions.

PMID- 27024862
TI  - Do you need a hearing test?  When everyone around you is mumbling, it may be time
      for a check-up.

PMID- 27024863
TI  - Flu shot linked to lower risk of heart problems, say Harvard researchers.

PMID- 27024864
TI  - Effective relief for hip and knee arthritis pain.

PMID- 27024865
TI  - Mediterranean now, better health later.

PMID- 27024867
TI  - Doctor's note.  Goal setting and your health.

PMID- 27024866
TI  - Ways to preserve youthful skin--without cosmetic surgery. You can't turn back the
      clock, but you can minimize the appearance of wrinkles and other signs of aging
      with these noninvasive techniques.

PMID- 27024868
TI  - Why having a pet is good for your health.  Could owning a pet help you live
      longer?  Possibly--if you get the right type of pet.

PMID- 27024869
TI  - Medicines to prevent breast cancer.  Many women who could benefit from breast
      cancer prevention drugs aren't taking them.

PMID- 27024870
TI  - Should you take a statin to prevent a heart attack or stroke? New guidelines may
      expand female candidates for these cholesterol-lowering drugs.

PMID- 27024871
TI  - What the Affordable Care Act means for you.  Here's how to make sense of your new
      benefits under the ACA.

PMID- 27024872
TI  - Diet-plus-exercise combo helps relieve knee osteoarthritis.

PMID- 27024873
TI  - Hormone therapy not recommended for chronic disease prevention.

PMID- 27024874
TI  - Walking may lower breast cancer risk.

PMID- 27024875
TI  - Can women get away with less frequent bone density screenings?

PMID- 27024876
TI  - Answers about aspirin. Should you be taking it? If so, when, how much, and what
      kind?

PMID- 27024877
TI  - Ask the doctor.  I'm a healthy 58-year-old man recently diagnosed with high blood
      pressure.  My doctor prescribed metoprolol, and my blood pressure is now in the
      normal range.  But I've started having trouble getting an erection. Could the
      medication be causing this problem, and if so, is there anything I can do about
      it?

PMID- 27024878
TI  - Ask the doctor. During a recent appointment, my cardiologist heard a sound in my
      neck and sent me for a ultrasound, which showed a narrowing in my carotid artery.
      The doctor said this means I'm at risk for a stroke. Because I'm already taking
      all the right medicines, his only recommendation was getting another ultrasound
      in a year. But if the narrowing gets worse and I have a stroke, won't that be too
      late?

PMID- 27024879
TI  - Lower your heart attack and stroke risk with a flu shot. Peak flu season is
      looming, so get your vaccination soon.

PMID- 27024880
TI  - Health tips for former smokers.  Quitting smoking is one of the most important
      things you can do for your health.  Learn how you can capitalize on these gains
      for years to come.

PMID- 27024881
TI  - Understanding cardiovascular pain.  What the location and severity reveals about
      your health.

PMID- 27024882
TI  - Fluid retention: what it can mean for your heart.  Fluid buildup indicates
      worsening heart failure.  Learn how to spot it and treat it early.

PMID- 27024884
TI  - Living longer: exercise at least as good as drugs.

PMID- 27024883
TI  - Coconut oil: supervillain or superfood? Learn what's behind coconut oil's sexy
      makeover.

PMID- 27024885
TI  - Stiffer arteries linked to amyloid plaques in the brain.

PMID- 27024886
TI  - Surgery after a stent: how risky?

PMID- 27024887
TI  - [RETROSPECTIVE DATA ANALYSIS OF THE PATIENTS WITH INFLAMMATORY JOINT DISEASES
      TREATED WITH GOLIMUMAB IN CROATIA].
AB  - Golimumab is a human monoclonal antibody which inhibits tumor necrosis factor
      alpha (TNF-alpha) and is approved for the treatment of inflammatory arthritides
      (rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis) when the
      conventional non-pharmacological and pharmacological therapies fail to cause
      remission or low disease activity. In this retrospective study there were
      included patients with rheumatoid arthritis, psoriatic arthritis and ankylosing
      spondylitis who were treated in Croatia with golimumab, from June 2011 to June
      2013. included and these retrospective data are compared with similar data from
      clinical trials and other available databases. Standard variables of disease
      activity and functional ability were observed. Results demonstrated significant
      efficacy of golimumab regarding lowring the disease activity and imrpving
      functional ability in pateints with these inflammatory rherumatic disease. In
      conclusion, in this retrospective study during two years treatment golimumab
      showed efficacy in decreasing disease activity and imrpove functional ability in
      patiemts with rheumatoid arthritis, psoriatic arthritis and ankylosing
      spondylitis.

PMID- 27024888
TI  - Looking forward.

PMID- 27024889
TI  - Determination and Correlation of Depth of Cure of a New Composite Resin Delivery
      System.
AB  - OBJECTIVES: To quantify the depth of cure (DOC) of a composite resin system using
      two different testing criteria. METHOD AND MATERIALS: The DOC testing employed
      two different experimental protocol: 1) Forty-eight previously extracted human
      molars were randomly assigned to four groups of twelve each (n = 12): Group 1
      SonicFill composite resin system, shade A1; Group 2 SonicFill, shade A3; Group 3
      Herculite Ultra composite resin, shade A1; Group 4 Herculite Ultra, shade A3.
      Cylindrical cavities (4.0 mm diameter and 10 mm depth) were prepared at the tooth
      CEJ, in a mesiodistal direction. The preparations were filled with each composite
      resin material in one bulk increment and polymerized with a LED light for 20
      seconds. After 5 minutes, the occlusal surfaces of the teeth (specimens) were
      ground flat until the composite was exposed in a transverse plane. The uncured
      (soft) composite was scraped away, using a "modified" ISO 4049 DOC specification,
      and the remaining cured (hard) material was measured. Three measurements, at
      different positions of the specimen, were performed, for a total of thirty-six
      measurements per specimen group. The measurements were averaged and divided by
      fifty percent, arriving at the final DOC for each specimen. 2) A DOC testing
      protocol was performed using a two-piece (4.0 mm x 10.0 mm) custom-made Teflon
      device (mold). The groupings duplicated the previous experimental protocol. The
      mold was filled with each composite resin material in one bulk increment to a 10
      mm length (depth). Excess composite material was removed, followed by placement
      of a Mylar strip over the external orifice. The composite resin specimen was
      light-polymerized for 20 seconds. Again, the uncured (soft) composite was scraped
      away, with the same measurement protocol followed as in method 1. Statistical
      analyses were conducted using ANOVA tests at a p < .05 level of significance.
      RESULTS: Statistical differences were exhibited between the two different DOC
      methodologies, extracted teeth versus the Teflon device. Considering each method,
      the SonicFilTM composite revealed significantly greater DOC compared to the
      Herculite Ultra composite resin. Also, significant differences were displayed
      between the Al compared to the A3 shades, with the A1 (lighter) shades exhibiting
      greater DOC. CONCLUSION: The prepped teeth seemed a more realistic DOC testing
      approach due to the variables of light interaction of the composite resin to
      either tooth substance (enamel/dentin) versus using the Tefion mold, although
      greater DOCs were recorded using the manufactured device. The SonicFill composite
      system did reveal greater DOC compared to the Herculite Ultra composite
      regardless of experimental method or material shade.

PMID- 27024890
TI  - [Formation of a single bone in the forearm in infected pseudoarthrosis of the
      proximal ulna].
AB  - PURPOSE: To present the successful results of the single-bone reconstruction
      technique in the forearm in a patient who sustained an ulnar fracture and
      underwent multiple osteosyntheses and failed grafts. CASE: Male patient,
      agricultural worker, who at age 39 sustained a left ulnar fracture. After 13
      years and 5 surgeries involving different types of osteosyntheses and failed
      grafts, which resulted in infection of the left ulnar pseudoarthrosis, we decided
      to do a single-bone reconstruction of the forearm. He did well and achieved good
      function. His current status is: 20 degrees  of forearm supination, full elbow
      and wrist flexion and extension, appropriate muscle strength, and he returned to
      his job without functional limitations. CONCLUSION: The single-bone forearm
      reconstruction technique is, in properly selected cases, an excellent surgical
      alternative when reconstruction or salvage of the thoracic limb is required.

PMID- 27024891
TI  - [Not Available].

PMID- 27024892
TI  - [Not Available].

PMID- 27024893
TI  - [Not Available].

PMID- 27024894
TI  - [Levosimendan in the treatment of acute heart failure; what are you using for
      patients?].

PMID- 27024895
TI  - Response by   Timothy Watson, Adele Pope, Niels van Pelt and Peter N. Ruygrok.

PMID- 27024896
TI  - A Second Opinion: A Case Narrative on Clinical Ethics Mediation.
AB  - Contrasting traditional and common forms if ethics consultation with bioethics
      mediation. I describe the case of a "second opinion" consultation in the care of
      a patient with advanced cancer for whom treatment was futile. While the initial
      ethics consultation, performed by a colleague, let to a recommendation that some
      may deem ethical, the process failed to involve key stakeholders and failed to
      explore the underlying values and reasons for the opinions voiced by various
      stakeholders. The process of mediation ultimately led to creative solutions in
      which all stakeholders could reach consensus on a plan of care.

PMID- 27024897
TI  - An amalgam-free world--are we and our patients ready?

PMID- 27024898
TI  - British Society of Prosthodontics Debate on the Implications of the Minamata
      Convention on Mercury to Dental Amalgam--Should our Patients be Worried?.
AB  - In 2013, the Minamata Convention on Mercury called for a global phase-down of
      amalgam use, with a view to reduce environmental mercury pollution. This will
      significantly impact UK dentistry, given the still extensive use of amalgam in
      U.K. general dental practice. However, until now there has been little national
      discussion or debate. In Spring 2015, The British Society of Prosthodontics
      dedicated a significant part of its Annual Conference to debating the
      implications of this issue. Clinical case examples were discussed with audience
      interaction and voting facilitated using innovative Audience Response System
      Technology. A remarkable range of concerns and opinions were given. The debate
      elicited specific concerns amongst clinicians regarding the suitability of
      mercury-free alternatives to amalgam; particularly where cavities are large and
      extend beneath the gingival anatomy. There are also anecdotal reports of Dental
      Foundation (DF) dentists not being adequately taught the use of dental amalgam in
      undergraduate dental schools. CPD/CLINICAL RELEVANCE: Many clinicians, especially
      those treating patients for whom moisture control is challenging, feel that
      amalgam should remain available for clinicians to choose in certain clinical
      circumstances for the restoration of posterior teeth, even in the event of a
      complete phase-down.

PMID- 27024899
TI  - Modern Endodontic Principles Part 4: Irrigation.
AB  - The complex anatomy of the tooth limits the ability to eradicate pathogens by
      mechanical means alone. Irrigation is the key to solving this problem. This paper
      highlights the importance of irrigation, the key irrigants available and methods
      of improving the performance of irrigants within the canal. CPD/CLINICAL
      RELEVANCE: To provide advice on which irrigants to use, how to use them
      effectively and safely and what to do if irrigants are extruded beyond the apex.

PMID- 27024900
TI  - Warfarin and Drug Interactions: Prescribing Vigilance.
AB  - A patient taking warfarin presented to the Oral Medicine Clinic at Liverpool
      University Dental Hospital, having been prescribed metronidazole and miconazole
      by his general dental practitioner (GDP) for his oral mucosal problem. He
      subsequently developed bruising on his torso following mild trauma. Having read
      the drug information leaflet provided with his metronidazole and miconazole, he
      noted the potential drug interactions between these and warfarin. He therefore
      stopped his warfarin. The details of this case are outlined, and the potential
      for significant drug interactions with warfarin are highlighted. The need for
      dental practitioners to be vigilant concerning drug interactions is emphasized,
      together with the importance of CPD in relation to drug prescribing. CPD/CLINICAL
      RELEVANCE: This case report, which is of relevance to all dental practitioners,
      highlights the importance of up-to-date medical and drug histories and the
      continuing awareness of potential drug interactions. In this case, patient
      intervention after checking drug information leaflets prevented serious
      consequences. The importance and potentially serious consequences of significant
      drug interactions needs to be understood.

PMID- 27024901
TI  - Pain Part 6: Temporomandibular Disorders.
AB  - TMDs are a complex collection of conditions which can have a significant impact
      on an individual's quality of life. The aetiology, diagnosis and management of
      TMDs will be described in this article with the hope of increasing a general
      dental practitioner's knowledge of these problems, thus helping them to institute
      simple, initial, conservative therapies for such patients. Diagnosis of TMDs can
      be simplified by following recent published clinical diagnostic criteria such as
      those outlined in this article. CPD/CLINICAL RELEVANCE: Pain and functional
      disturbances related to TMDs are common and require simple and pragmatic
      interventions for most patients. After providing a diagnosis, reassure patients
      that they do not have a sinister disease, and explain that the condition is
      usually self-limiting.

PMID- 27024902
TI  - Mouth Cancer for Clinicians Part 7: Cancer Diagnosis and Pre-treatment
      Preparation.
AB  - A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck
      cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all
      publications contain robust evidence. We endeavour to encapsulate the most
      important of the latest information and advances now employed in practice, in a
      form comprehensible to healthcare workers, patients and their carers. This series
      offers the primary care dental team in particular, an overview of the
      aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth
      cancer, the functional and psychosocial implications, and minimization of the
      impact on the quality of life of patient and family. CLINICAL RELEVANCE: This
      article offers the dental team an overview of diagnosis, diagnostic and pre
      treatment procedures.

PMID- 27024903
TI  - Nutrition and Periodontal Disease.
AB  - The identification of inflammatory periodontal disease and education in local and
      systemic risk factors and their management forms the foundation of the treatment
      of this disease. Nutrition is potentially a modifiable risk factor that could
      drive or abrogate the underlying oxidative stress in periodontitis. As research
      in this area is still in its infancy, clinical guidance on the delivery of
      dietary advice for susceptible patients is scarce. This paper will explain the
      possible mechanisms linking nutrition and periodontal disease, as well as the
      guidelines currently available to the dental profession. CPD/CLINICAL RELEVANCE:
      With a growing evidence base, an appreciation of the links between nutrition and
      inflammatory periodontal disease can help guide clinicians in educating patients
      on this potentially important modifiable risk factor.

PMID- 27024904
TI  - Extra-oral Appliances in Orthodontic Treatment.
AB  - Extra-oral appliances are used in orthodontics to apply forces to the jaws,
      dentition or both and the popularity of these appliances is cyclical. Although
      the use of retraction headgear for the management of Class II malocclusion has
      declined over the last 20 years with the refinement of non-compliance approaches,
      including temporary anchorage devices, headgear still has a useful role in
      orthodontics. The use of protraction headgear has increased as more evidence of
      its effectiveness for the treatment of Class lIl malocclusion has become
      available. This paper describes the mechanics and contemporary uses of headgear
      in orthodontics for primary care dentists and specialist orthodontists.
      CPD/CLINICAL RELEVANCE: Extra-oral appliances have specific uses in orthodontic
      biomechanics. Clinicians using retraction headgear and protraction headgear
      should be familiar with their clinical indications, the potential problems and
      how these can be avoided.

PMID- 27024905
TI  - Benzodiazepines: Sedation and Agitation.
AB  - Dental anxiety is common and frequently poses a barrier to necessary dental
      treatment. The increasing availability of conscious sedation in dental practice
      has made treatment much more accessible for anxious patients. At present,
      benzodiazepines are the most commonly used drugs in sedation practice and provide
      a pleasant experience for most, but not all, patients. An understanding of the
      mechanism of action of benzodiazepines should inform our practice and deepen our
      understanding of why and how sedation may fail. CPD/CLINICAL RELEVANCE: As an
      increasing number of dentists provide sedation for their patients an update on
      benzodiazepines is timely.

PMID- 27024906
TI  - A Case of Undiagnosed Harlequin Syndrome Presenting in General Dental Practice.
AB  - Harlequin syndrome is a rare, clinically striking syndrome characterized by
      distinctly demarcated asymmetric facial flushing and sweating. It may be of
      idiopathic aetiology or caused by demonstrable ipsilateral damage to the
      sympathetic nervous system. A case is described where a patient presented to her
      general dental practitioner complaining of distinctly demarcated unilateral
      facial flushing and sweating. Onward referral resulted in a diagnosis of
      Harlequin syndrome. CPD/CLINICAL RELEVANCE: This article highlights the
      neurological signs and symptoms of Harlequin syndrome, making it easier to
      recognize if it presents in general dental practice.

PMID- 27024907
TI  - Clinical Challenges Q&A. 17. Facial Lesions and Mouth Ulceration.

PMID- 27024908
TI  - Technique Tips--Composite Edge Bonding--the Reverse Triangle Technique.

PMID- 27024909
TI  - [New approaches to the treatment of the flavivirus infections].
AB  - Since spontaneous mutagenesis and quasi-species rearrangements of the RNA
      containing viruses, as well as an absence of both viral and cellular RNA
      reparation systems, causes resistance to originally effective antiviral drugs,
      combination therapy with nucleoside and non-nucleoside inhibitors of the viral
      enzymes in combination with immunomodulators is recommended. The use of specific
      immunoglobulins does not result in complete elimination of the flaviviruses but
      rather in possible antibody-dependent enhancement of the flavivirus infection by
      means of increased penetration of complexes of virions with specific antibodies
      into cells with receptors for Fc-fragments of immunoglobulins.

PMID- 27024910
TI  - [Anti-hepatitis B vaccination and postvaccinal immunity stimulation in patients
      with chronic obstructive pulmonary disease].
AB  - The problem of the anti-hepatitis B vaccination of patients with chronic
      obstructive lung disease (COPD) was discussed due to the lack of studies
      concerning the developing of the postvaccinal immunity, especially when
      vaccination is combined with the immunomodulating treatment. The data on the
      vaccination safety and its influence on the clinical course of COPD are also
      insufficient. Therefore, in this work we investigated the efficiency of the
      antihepatitis B vaccination in adults with chronic obstructive pulmonary disease
      under the treatment with the immunomodulating Affonoleikin drug. A total of 93
      patients were tested including 59 patients with severe and moderate COPD (aged
      from 35 to 65 years). 34 of these 59 patients were vaccinated against hepatitis B
      (Kombioteh) according to 0-1-6 month scheme, and 25 of them were vaccinated
      against hepatitis B during the treatment with Affinoleikin. The control group,
      consisted of 34 healthy patients. Our study demonstrated good tolerance and high
      immune efficiency of the anti-hepatitis B vaccine. However, after the first
      vaccination the level of HBs-AT was below protective level in patients with COPD
      compared to healthy patients. Also, 64 to 70 % of patients with COPD were
      seronegative excluding the patients receiving the Affinoleikin treatment, whose
      antibody titer was protective after the first vaccine dose, but did not reach the
      level typical of healthy patients. After the second vaccination we detected low
      and medium protective antibody levels in 58.9% of patients from the 1st group,
      whereas 41% were seronegative. Introduction of the third vaccine-dose led to fast
      and significant increase in the antibody level mainly in high concentrations with
      100% seroconversion in all patients. Combined antihepatitis B vaccination and
      Affinoleikin treatment in patients with COPD leads to faster biosynthesis of HBs-
      AT in protective concentrations and decrease of seronegative response, but it has
      no effect on frequency and type of general and local postvaccinal response.

PMID- 27024911
TI  - [Rapid spread of the HIV-1 circular recombinant CRF02-AG in Russia and
      neighboring countries].
AB  - The spread of the HIV-1circular recombinant CRF02-AG in countries of the former
      Soviet union (Commonwealth of Independent States, CIS) was studies using partial
      and full genome sequences. The full-genome sequence of the CRF02-AG recombinant
      circulating in Russia was obtained for the first time. A Global phylogenetic tree
      of CRF02-AG full-genome sequences was constructed. Three distinct groups of the
      sequences were detected as clustered by the geographical location (CIS, South
      Korea, and France), which is indicative of the single-virus introduction in each
      of the regions mentioned above. The CIS cluster exhibiting minimum genetic
      diversity was, therefore, relatively young. The phylogenetic analysis of the env
      gene sequences within the CIS cluster made it possible to clearly discriminate
      three branches: two of Russian and one of Uzbek origin. The low genetic diversity
      within the two Russian subclusters provides evidence of at least two recent
      independent introductions of the CRF02-AG recombinant from Central Asia into
      Russia. This work was performed within the framework of the 7th Federal Research
      Program (FP&), Project EURIPRED (European Research Infrastructures for Poverty
      Related Diseases), grant agreement No.312661.

PMID- 27024912
TI  - [Serodiagnosis in the surveillance of the influenza virus circulation during the
      development of the pandemic caused by the A (H1N1)pdm09].
AB  - The goal of this work was to present the data of the study of the peculiarities
      of the generation factors of humoral immunity in the response to the infection
      with the pandemic influenza A (HIN1) pdmO9 in patients with different
      epidemiological anamnesis. High ability of the influenza viruses to spread over
      closed communities and the transfer of the maternal antibodies to babies,
      including a pandemic strain of the influenza virus A (H1N1) pdm09, was confirmed.
      The results of this study showed that the immune response to the surface antigens
      of the influenza virus (hemagglutinin and neuraminidase) was formed during the
      natural infection with the pandemic strains of the influenza A (H1N1) pdm09 in
      more than a half of the cases simultaneously.

PMID- 27024913
TI  - [[Antiviral activity of the interferon beta 1a].
AB  - The antiviral activity of the interferon beta Ia was studied using the example of
      the antiviral activity of the drugs interferon beta Ia Genfaxon and Rebif for the
      influenza and herpes. A pronounced antiviral effect of the drugs against
      influenza and herpes viruses was-shown far the first time.

PMID- 27024914
TI  - [Prevalence and incidence of the infections among blood donors in Russia].
AB  - The prevalence and incidence of the infections among Russian blood donors in 2010
      2012 was determined. The estimated residual risk of the transfusion infection was
      as follows: for HIV - 16.2, HCV - 33.7; HBV - 97.1 per 1 million donations. In
      the information system of the blood service AIST data should be divided based on
      the posi- tive results of screening and confirmatory tests for markers of the
      infection. High risk of the transfusion infection with HIV, hepatitis B and C
      stimulates the active implementation of the measures for increasing the safety of
      blood: the selection of donors, increasing the sensitivity of infections
      screening methods, inactivation of patho- gens in blood components, and
      transfusion management appointment at the clinic.

PMID- 27024915
TI  - [Strategy of synonymous codon usage in encoding sequences of the tick-borne
      encephalitis virus].
AB  - Three basic genotypes of the tick-borne encephalitis virus have wide geographical
      spread; several strains have local spread. In this work, we studied the strategy
      of the synonymous codon usage in basic genotypes by means of calculation of
      relative synonymous codon usage values for each complete encoding sequences of
      viruses. Then, these values were analyzed by methods of the discriminant
      analysis. In the result of this work the conclusion about the available
      distinctions in the strategy of synonymous codon usage of various genotypes tick
      borne encephalitis viruses was made.

PMID- 27024916
TI  - [Development of the disease in marmot at the intranasal infection with the
      monkeypox virus].
AB  - In experimental study the sensitivity of the Marmota bobak species to the
      monkeypox virus (MPXV) with the intranasal (i/n) infection was tested. It was
      demonstrated that 50% of the infective dose (ID50) of the MPXV on external
      clinical signs of the disease was 2.2 Ig plaque forming units (PFU). The
      percentage of the marmot mortality is slightly dependent on the infecting dose of
      the MPXV, therefore it is not possible to correctly determine the value of 50 %
      fatal dose (FD50) for these animals. The most pronounced external clinical signs
      of the disease were obtained in the marmots: pox-like skin rash throughout the
      surface of the body and mucous membranes, purulent discharge from the nose,
      lymphadenitis, discoordination, tremor of the extremities, fever, increased
      aggression, and ruffled fur. In the course of experiments intended to determine
      the dynamics of the accumulation of the MPXV in various organs, tissues, and
      blood serum of marmot infected i/n with dose of 3.7 Ig PFU, it was found that the
      trachea, lungs, and the bifurcation lymph nodes are the primary target organs.
      The trachea, lungs, nasal mucosa membrane, and skin are the organs with maximal
      virus replication recorded at 5, 7, 9, and 12 days after the infection. The
      transfer of the MPXV into the secondary target organs (nasal mucosa membrane,
      brain, spleen, duodenum, adrenal glands, and skin) was carried out in marmots
      with lymphogenic and hematogenic ways of the dissemination of the infection.

PMID- 27024917
TI  - [Comparative research into sensitivity and specificity of immune-enzyme analysis
      with chemiluminescence and colorimetric detection for detecting antigens and
      antibodies to avian influenza viruses and newcastle disease].
AB  - The goal of this work was to demonstrate the results of the development of the
      enzyme-linked immunosorbent tests with chemiluminescence detection and
      colorimetric detection of specific viral antigens and antibodies for identifying
      the avian influenza and the Newcastle disease viruses: high sensitivity and
      specificity of the immuno- chemiluminescence assay, which are 10-50 times higher
      than those of the ELISA colorimetric method. The high effectiveness of the
      results and the automation of the process of laboratory testing (using a
      luminometer) allow these methods to be recommended for including in primary
      screening tests for these infectious diseases.

PMID- 27024918
TI  - [PCR study of the human herpes virus type 6 and other viruses of the herpes group
      in eye diseases].
AB  - To study the role of the HHV-6 type in the development of eye diseases PCR tests
      of blood (152), cornea biopsies (61), and intraocular fluids (11) for HHV-6 and
      other viruses of the herpes group (HSV type 1 and 2, CMV, EBV) were conducted. It
      was found that the HHV-6, along with other representatives of the Herpesviridae,
      can be detected in patients with different clinical forms of ophthalmopathology
      (174 patients were surveyed). Viral DNA was detected in blood, cornea, and in the
      anterior chamber fluid. The obtained data allow that the HHV-6 to be suggested as
      a possible cause of the ophthalmic herpes along with the other viruses of this
      group. It makes finding the virus DNA an essential step towards setting the
      etiologic diagnosis of the ophthalmological patients.

PMID- 27024919
TI  - [Evaluation and prognosis of health loss among able-bodied population: risks and
      problems in modernization of Russian regions].
AB  - The authors justified a method to evaluate and forecast risk of medical and
      demographic losses connected with influence of variable environmental factors on
      mortality and morbidity parameters among able-bodied population Suggested methods
      and approaches were tested and exemplified by Far East and North Caucases regions
      orientated to advanced and modernization development strategies. Mathematic
      modelling results helped to characterize relationships between environmental and
      social economic risk factors with health responses. These factors appear to form
      annua probable regional losses varying from tens to over thousand of deaths among
      economically active individuals and up to several hundreds of disablement cases.
      Progressive labor deficit and worse health among economically active populatior
      appeared to be major obstacles on the way to modernization of Russian regions.
      The article is prepared within scientific program by Perm' State National
      Research University according to task giver by RF Education and Science Ministry
      in 2015 (project N 929, head--E.B. Plotnikova).

PMID- 27024920
TI  - [Forming a community at risk for circulatory system diseases among workers
      engaged into underground mining].
AB  - Forming a community at risk for circulatory system diseases will increase
      efficiency of medical and prophylactic measures on managing risk of arterial
      hypertension. Epidemiologic analysis helped to reveal reliable connection between
      arterial hypertension predictors and work conditions of mining machine operators
      and supported actualization of high occupational risk suggested in a priori
      evaluation. Mathematic modelling helped to forecast increase in the disease
      probability: with noise level of 94 dB after 10 years of work, 17.9% of workers
      are expected to have arterial hypertension preventing from further occupational
      activity. Forecasting results of arterial hypertension probability help to form
      risk groups for medical and preventive technologies managing occupational risk,
      and predictors enable to specify necessity of individual medical preventive
      measures.

PMID- 27024921
TI  - [Immune and genetic markers revealed in women working in technical rubber goods
      production].
AB  - Medical examination covered female workers engaged into chemical production of
      technical rubber goods, under combined exposure to chemicals (nitrogen oxides,
      carbon oxide) and noise exceeding MAC by 3.7-27.5%. Findings are increased
      phagocytary activity, lower level of serum IgM and IgG, suppressed expression of
      CD25 and CD95 T-cell receptors, and slower apoptosis induced via Fas receptor-
      all those indicators associated with work conditions. The disorders revealed are
      actualized on a basis of genetic variability features of the females, that is
      characterized by prevalence of mutant allels of FAS and TNFR genes with minor
      homozygous phenotype.

PMID- 27024922
TI  - [Inhalation toxicity of nanodispersed manganese oxide aerosol].
AB  - The article presents results of experimental study concerning acute inhalation
      toxicity of nanodispersed manganese oxide widely used in novelty goods
      production. During the technology process, nano-dimensional manganese oxide
      aerosol could appear in workplace air--that causes danger of the workers'
      inhalation exposure. Findings are that the studied substance is a nanomaterial
      with prevalent fihiform particles measuring 15-29 nm. The substance is acutely
      toxic when inhaled as an aerosol. Cl50 for 4-hour exposure for Wistar rats equals
      120 mg/m3 (1 jeopardy class). Clinical manifestations of acute intoxication are
      mostly irritative and neurotoxic effects supported by morphologic studies.
      Histopathologic changes in brain tissue are cerebellar ischemia with dilated
      perecellular spaces, faveolate appearance.

PMID- 27024923
TI  - [Prevention of circulatory system diseases in underground mining workers].
AB  - The article covers results of preventive measures in workers engaged into
      underground mining. Those measures are aimed to prevent occupationally mediated
      health disorders resulting in circulatory diseases. The prophylaxis was proven
      effective on premorbid condition--that was demonstrated in reliable decrease of
      cause-effect relationship intensity for health disorders in workers subjected to
      prophylactic measures. Transitory disablement morbidity due to cicrulatory system
      diseases decreased. Situational modelling of risk changes for the studied group
      demonstrated changes of diseases risk under medical prophylactic measures. After
      the prophylaxis, the risk demonstrated 3.1 times decrease.

PMID- 27024924
TI  - [Immune and genetic changes in workers exposed to industrial noise and dust].
AB  - Comparative analysis covered immune genetic parameters in nonferrous metallurgy
      workers. The authors demonstrated differences in immune genetic profile between
      male and female workers, under exposure to combination of occupational hazards:
      noise and dust. Analysis of gene polymorphism revealed predominant disorders in
      the female workers, concerning criterion of prevalence for minor allele of genes
      in 1 and 2 phases of detoxication, neuro-endocrine regulation, lipid and energy
      metabolism, genes of immune regulation and apoptosis.

PMID- 27024925
TI  - [Dynamics of hormonal state in titanium and magnesium production].
AB  - The authors demonstrated that work conditions for main occupations (puncher,
      cutter, sorter, melter) of titanium-magnesium production are characterized by
      combined exposure to chemical and physical environmental hazards: titanium oxide
      aerosol, industrial noise, local vibration, heating microclimate, work hardiness.
      The work conditions are assessed as hazardous (class 3.2-3.4), work process as
      hard (class 3.2). The female workers appeared to have reliable increased of AST
      and prolactine, with lower serum estradiol and FSH levels, if compared to
      reference group. The workers demonstrated increase in LH, SHBG, prolactine and
      estradiol, with decrease of free testosterone. That can result in reproductive
      disorders of men and women, as well as remote effects in offspring.

PMID- 27024926
TI  - [Development of lipids and carbohydrates metabolism disorders caused by drinkable
      water with high content of chlorine organic compounds].
AB  - Evaluation of effects caused by environmental peroral exposure to chlorine
      organic compounds revealed that individuals with AG variation of HTR2A gene are a
      community with increased sensitivity to chloroform and a risk group for lipid and
      carbohydrates metabolism disorders. Individual risk of endocrine disorders (ICD:
      E67.8 excessive nutrition and E66.0 obesity) in these individuals is higher than
      in general population exposed to chloroform at residence (HQ1.72). Serum
      serotonin level, that is functionally connected with HTR2A gene, is 1.3 times
      lower vs. the reference group value.

PMID- 27024927
TI  - [Follow-up in coal miners suffering from lumbo-sacral radiculopathy].
AB  - The results of a retrospective dynamic monitoring in 1976-2014 of the workers of
      coal mines of main (n = 1732) and auxiliary (n = 1059) occupations, with
      diagnosed occupational sciatica (OS) in the center of occupational medicineare
      viewed. It was found that the workers of the main occupationson average of 3
      years earlier than initially treated at the center of occupational medicine, and
      occupational disease OS sets for them 1.5-2 years earlier. The analysis of the
      formation of risk groups depending on the diagnosis and treatment of the primary
      analysis of the incidence of OS.

PMID- 27024928
TI  - [Early clinical changes and emotional burnout of police officers].
AB  - The authors evaluated adaptational potential of cardiovascular system in 110
      police officers considered as apparently healthy and fit for service, working in
      psychoemotional stress with exertion of body adaptational functions and health
      disorders development. Adaptational potential of cardiovascular system served as
      an indicator of adaptive body reactions. Prenosologic states diagnosis determined
      risks of main general pathologic syndromes in individuals with satisfactory and
      disordered adaptation. Leading symptoms of emotional burnout were assessed and
      appeared to depict depletion of psychoemotional processes in occupational
      activity of individuals with various adaptation states. The study results enable
      to connect adaptation disorder with risk of main general pathologic syndromes and
      occurrence of emotional burnout symptoms. The prenosologic states appearing could
      be considered as an adaptation way towards specific conditions of occupational
      activity of police officers.

PMID- 27024929
TI  - [Evaluation of workers' periodic medical examinations quality].
AB  - The results of the study to evaluate satisfaction with the quality of the
      periodic medical examinations of workers (PME) are analyzed. In survey 45
      employers, 120 doctors performing PME and 107 workers participated. The results
      show low satisfaction with the quality of the PME. Employers in 60% of cases
      noted the formal conduct of PME. Doctors in 40.8% of cases as the main defect in
      the organization of PME mentioned the lack of quality control system. According
      to the workers' opinion, the poor quality of PME recognized in 30.8% of cases;
      however, 54.2% of the workers noted the good organization of the PME.

PMID- 27024931
TI  - [Buhtiyarov I V, Izmerov N F, Shigan E E 31st International Congress in
      Industrial medicine].

PMID- 27024930
TI  - [Resolution of "Occupation and Health" XIII Russian Congress with international
      participation].

PMID- 27024932
TI  - Reading Dogs Reading Us.

PMID- 27024933
TI  - Benjamin Franklin's Wife's Apoplexy and Mid-Eighteenth Century Medicine.

PMID- 27024934
TI  - WARD H. GOODENOUGH.

PMID- 27024935
TI  - Philosophical Intelligence: Letters, Print, and Experiment during Napoleon's
      Continental Blockade.
AB  - This essay investigates scientific exchanges between Britain and France from 1806
      to 1814, at the height of the Napoleonic Wars. It argues for a picture of
      scientific communication that sees letters and printed texts not as separate
      media worlds, but as interconnected bearers of time-critical information within a
      single system of intelligence gathering and experimental practice. During this
      period, Napoleon Bonaparte's Continental System blockade severed most links
      between Britain and continental Europe, yet scientific communications continued-
      particularly on electrochemistry, a subject of fierce rivalry between Britain and
      France. The essay traces these exchanges using the archive of a key go-between,
      the English man of science Sir Charles Blagden. The first two sections look at
      Blagden's letter-writing operation, reconstructing how he harnessed connections
      with neutral American diplomats, merchants, and the State to get scientific
      intelligence between London and Paris. The third section, following Blagden's
      words from Britain to France to America, looks at how information in letters
      cross-fertilized with information in print. The final section considers how
      letters and print were used together to solve the difficult practical problem of
      replicating experiments across the blockade.

PMID- 27024936
TI  - Log Books and the Law of Storms: Maritime Meteorology and the British Admiralty
      in the Nineteenth Century.
AB  - This essay contributes to debates about the relationship between science and the
      military by examining the British Admiralty's participation in meteorological
      projects in the first half of the nineteenth century. It focuses on attempts to
      transform Royal Navy log books into standardized meteorological registers that
      would be of use to both science and the state. The essay begins with a discussion
      of Admiralty Hydrographer Francis Beaufort, who promoted the use of standardized
      systems for the observation of the weather at sea. It then examines the
      application of ships' logs to the science of storms. The essay focuses on the
      Army engineer William Reid, who studied hurricanes while stationed in Barbados
      and Bermuda. Reid was instrumental in persuading the Admiralty to implement a
      naval meteorological policy, something the Admiralty Hydrographer had struggled
      to achieve. The essay uses the reception and adoption of work on storms at sea to
      reflect on the means and ends of maritime meteorology in the mid-nineteenth
      century.

PMID- 27024937
TI  - Ark and Archive: Making a Place for Long-Term Research on Barro Colorado Island,
      Panama.
AB  - Barro Colorado Island (BCI), Panama, may be the most studied tropical forest in
      the world. A 1,560-hectare island created by the flooding of the Panama Canal,
      BCI became a nature reserve and biological research station in 1923.
      Contemporaries saw the island as an "ark" preserving a sample of primeval
      tropical nature for scientific study. BCI was not simply "set aside," however.
      The project of making it a place for science significantly reshaped the island
      through the twentieth century. This essay demonstrates that BCI was constructed
      specifically to allow long-term observation of tropical organisms--their complex
      behaviors, life histories, population dynamics, and changing species composition.
      An evolving system of monitoring and information technology transformed the
      island into a living scientific "archive," in which the landscape became both an
      object and a repository of scientific knowledge. As a research site, BCI enabled
      a long-term, place-based form of collective empiricism, focused on the study of
      the ecology of a single tropical island. This essay articulates tropical ecology
      as a "science of the archive" in order to examine the origins of practices of
      environmental surveillance that have become central to debates about global
      change and conservation.

PMID- 27024938
TI  - Medieval Round Churches and the Shape of the Earth.
AB  - There is a unique cluster of four medieval round churches, linked by a simple
      geometry, on Bornholm Island in the Baltic Sea. Why so many and why so close
      together? Immediate simple answers are "Just by chance" and "For no reason." Why
      are the churches round? "Defense." This essay proposes another hypothesis for
      this unique situation: the churches are astronomical observatories, meant to
      solve a scientific problem (Is the Earth really spherical?) and a practical
      problem (How far is it to sail west to the Orient?). The capacity and desire to
      find answers, together with other practical needs related to astronomy, can
      better explain these round churches' special architecture. The geometry that
      connects them fits the ideal pattern with an angular accuracy of 1 minute of a
      degree. The round churches may be the earliest astronomical observatories in
      Christian Europe; other hypotheses have been shown to be untenable. Their
      location provides for a good method to estimate the Earth's extent in the east
      west direction, seemingly the earliest such measurements.

PMID- 27024939
TI  - Introduction: Bridging Concepts.
AB  - How can those in the history of science, history of technology, and economics
      communicate more with each other than they are accustomed? How can they become
      more globally oriented? While these three disciplines today have more convergent
      interests than in the past, there is still a large potential for further exchange
      and involvement to explore and exploit. The contributors to this Focus section
      discuss a number of concepts that may serve as tools to bring these three
      disciplines more closely together and ease their evolution in a less Eurocentric
      direction. These concepts include trading zones, interaction and formalization,
      production, and machines and self-organization.

PMID- 27024940
TI  - Trading Zones in Early Modern Europe.
AB  - This essay adopts the concept of trading zones first developed for the history of
      science by Peter Galison and redefines it for the early modern period. The term
      "trading zones" is used to mean arenas in which substantive and reciprocal
      communication occurred between individuals who were artisanally trained and
      learned (university-trained) individuals. Such trading zones proliferated in the
      sixteenth century. They tended to arise in certain kinds of places and not in
      others, but their existence must be determined empirically. The author's work on
      trading zones differs from the ideas of Edgar Zilsel, who emphasized the
      influence of artisans on the scientific revolution. In contrast, in this essay,
      the mutual influence of artisans and the learned on each other is stressed, and
      translation is used as a modality that was important to communication within
      trading zones.

PMID- 27024941
TI  - Formalization and Interaction: Toward a Comprehensive History of Technology
      Related Knowledge in Early Modern Europe.
AB  - Recent critical approaches to what has conventionally been described as
      "scientific" and "technical" knowledge in early modern Europe have provided a
      wealth of new insights. So far, the various analytical concepts suggested by
      these studies have not yet been comprehensively discussed. The present essay
      argues that such comprehensive approaches might prove of special value for long
      term and cross-cultural reflections on technology-related knowledge. As heuristic
      tools, the notions of "formalization" and "interaction" are proposed as part of
      alternative narratives to those highlighting the emergence of "science" as the
      most relevant development for technology-related knowledge in early modern
      Europe.

PMID- 27024942
TI  - Producing (in) Europe and Asia, 1750-1850.
AB  - This essay argues for understanding and investigating the history of production,
      not primarily as a quantifiable economic phenomenon, but as a history of practice
      that involves the human senses, culture, governance, and material engagement. The
      vehicle it uses to make its case focuses on a brief examination of production
      cycles involving salts in various parts of Eurasia during the century that runs
      from approximately 1750 to 1850. The essay's approach suggests a history of
      production in Eurasia that was both locally variegated and transregionally
      networked. It further involved the interaction between people and their
      sociomaterial environments, the latter understood as the evolving outcome of
      interplay between material elements and processes; culturally rooted tastes and
      values; and variously organized efforts to stimulate, manage, and pursue cycles
      of production and use. This essay further reflects on how contemporary
      commentators and present-day historians have (re)configured the geography of
      these practices in a way that emphasizes divergence between Europe and Asia. Part
      of this reflection involves looking at what can happen when the historical
      investigation of production is based on economic analysis. So too does it involve
      thinking about the potential pitfalls of framing comparative histories.

PMID- 27024944
TI  - Eloge. IVOR GRATTAN-GUINNESS 1941-2014.

PMID- 27024943
TI  - On Machines, Self-Organization, and the Global Traveling of Knowledge, circa 1500
      1900.
AB  - How and why does knowledge move from one place in the world to another? This is
      the key question of this contribution to the Focus section. The essay discusses a
      number of concepts concerning the global traveling of knowledge that are relevant
      for both preindustrial and industrial times. It proposes to modify and extend the
      metaphor of the "machine," introduced by James McClellan and Francois Regourd.
      Global traveling of knowledge was in historical reality often not only
      coordinated by "colonial" (or rather "imperial") machines but also by machines of
      a "commercial" or "religious" nature. Moreover, flows of knowledge could also be
      moved by forces from below, which may be analyzed by means of the concept of
      "self-organization." A range of examples illustrates that these concepts can be
      usefully applied in European as well as outer-European contexts.

PMID- 27024945
TI  - Growing problem of allergy in population of children and adolescents living in
      Polish cities.
AB  - Allergy is a worldwide medical problem and prevalence of allergic diseases is on
      the rise. In the study a population of 7494 children and adolescents living in
      Cracow responded to a questionnaire based on the ISAAC study complemented with
      questions concerning food allergy. 49.1% of respondents reported symptoms
      suggestive of allergic disease. 52.7% of them (25.9% of respondents in total) had
      not received any treatment despite the reported symptoms. The most frequently
      reported allergic disease was allergic rhinitis followed by atopic dermatitis,
      asthma, food allergy and allergic contact dermatitis. In the adolescents group
      allergic rhinitis was followed by asthma. 487 voluntary applicants were further
      analysed in order to confirm specific allergic disease. Given the final
      diagnosis, allergic rhinitis was also the most common disease. Interestingly in
      both categories (preliminary and final diagnoses) we noticed that it is
      substantially more frequent in the older group which in our opinion can be linked
      to the impact of polluted urban environment but there is a need for further
      research in this area.

PMID- 27024946
TI  - The influence of pulmonary rehabilitation in the Wieliczka Salt Mine on asthma
      control--preliminary results.
AB  - According to asthma treatment guidelines the main goal of pulmonary
      rehabilitation is optimum asthma control. The Asthma Control Test (ACT) is a
      standardised five-item questionnaire for the assessment of asthma control. The
      study compares the pre- and post-treatment (subterraneotherapy) ACT score with
      other conventional respiratory parameters. The study included 21 patients with
      bronchial asthma who underwent a 3-week long subterraneotherapy programme in the
      'Wieliczka' Salt Mine. The patients completed the ACT questionnaire before and 2
      weeks after subterraneotherapy. At the same time, they underwent testing for
      concentration of nitric oxide in exhaled breath (FENO), peak expiratory flow
      (PEF) and spirometry. Subterraneotherapy influenced significantly the change of
      MEF75 (p = 0.03255) and improvement of ACT score (N = 21, p = 0.0016). The
      differences in other parameters were not statistically important, but in the case
      of FEV1 and VC parameters, the differences found were close to the statistical
      significance (0.05 < p < 0.10). The differences of results before and after
      subterraneotherapy were higher in the group assigned as patient with poor or
      moderate asthma control (ACT score < 20, N = 10) than in the group with good
      control of asthma (ACT score >= 20, N = 11). For parameters FEV1, VC, MEF75 and
      ACT score the improvement was significantly higher in the poor control group. The
      pulmonary rehabilitation programme combined with subterraneotherapy helps to
      control asthma especially in patients suffering from poorly or moderate
      controlled asthma.

PMID- 27024947
TI  - Drug-specific in vitro secretion of IFNgamma in the diagnosis of drug-induced
      exanthemas: electrochemiluminescence assay versus previously used diagnostic
      methods.
AB  - The in vitro diagnosis of delayed drug hypersensitivity reactions remains a
      research problem. We measured drug-specific IFNgamma release in peripheral blood
      mononuclear cells sampled from patients with drug-induced maculopapular exanthema
      and the age- and sex-matched control group. This is the first study to directly
      cross-compare an ultrasensitive assay based on an emerging
      electrochemiluminescence technology (ECL), the standard lymphocyte proliferation
      assay and three following tests detecting IFNgamma at different steps of its
      production: intracellular in CD3+CD4+ cells (flow cytometry), secretion at the
      single cell level (enzyme-linked immunospot assay), bulk content in cell culture
      supernatant (enzyme-linked immunosorbent assay, ELISA). The highest rate of drug
      positive responses were recorded for ELISA and ECL tests (56.25%). No false
      positive responses were observed--all tests were negative in the control group.
      We demonstrated that IFNgamma-detecting ELISA is not less efficient than ECL
      test, however, it is easily available and cheap, which makes it a potential
      method of choice in the future.

PMID- 27024948
TI  - [Basophil activation test--a practical approach to diagnosis of common
      respiratory allergy].
AB  - BACKGROUND: The diagnosis of immediate allergy is based on clinical data, skin
      prick tests (SPT), and measurements of allergen-specific IgE (sIgE). Basophil
      activation test (BAT) can supplement these methods and obviate their
      disadvantages, and possibly replace allergen challenge tests, such as a nasal
      provocative test (NPT). In this study, we assessed the influence of different
      storage times on BAT results. Futhermore, we compared the results of SPT, sIgE
      and NPT against BAT for common aeroallergens. METHODS: BAT was performed in
      twelve patients with allergic rhinitis sensitized to birch pollen or mites 1, 4
      and 24 hours after blood sampling. CD63 was used as an activation marker. Three
      serial 10-fold dilutions (1:1, 1:10, 100) of allergen extract were employed. The
      further 10 individuals allergic to mites undergone complete diagnostic evaluation
      including SPT, sIgE measurements, NPT and BAT. Receiver operating characteristic
      (ROC) curves were used to compare the diagnostic techniques and tests conditions.
      RESULTS: Basophil activation expressed as stimulation index did not decline
      significantly up to 24h. Exposure to causal allergens resulted in a dose
      dependent increase in expression of CD63 on peripheral blood basophils in tested
      individuals. We did not observed substantial differences in results of the
      investigated diagnostic methods determined by a ROC analysis. CONCLUSIONS: Flow
      assisted diagnosis of common respiratory allergy relies upon allergen-induced
      activation of blood basophils can be a useful approach to determine the
      clinically relevant allergen in sensitized individuals. BAT with inhaled
      allergens can be performed within 24 hours after blood collecting into a tube
      with EDTA. Allergen suitable for NPT in appropriate dilutions is a good reagent
      for use in BAT.

PMID- 27024949
TI  - [Squamous epithelium in the nasal cytology].
AB  - Nasal mucosa cytology is an additional examination useful to differentiate
      chronic rhinitis in allergological and laryngological diagnostics, including
      chronic sinusitis. The aim of the study was to estimate the cytological picture
      in a group of patients with the highest percentage of squamous epithelia,
      suggesting the atrophic rhinitis. The analysis was carried out on the basis of
      cytological results performed in 3055 patients diagnosed because of chronic
      rhinitis. Among these patients, in 31 individuals the higher percentage (30% -
      76%) of squamous cells was found. In six patients, the clear predominance of
      squamous cells over ciliated and goblet cells (3:1) was reported. Only in three
      patients the increased percentage in eosinophils was stressed (3%, 5% and 9%
      respectively). No basic and metaplastic cells were observed in the studied
      cytograms. The squamous cells occurred probably as a result of normal mucosa
      damages during the different inflammatory changes, both allergic and non
      allergic, the impact of toxic agents, irritants (including nasal drops). The
      higher percentage of squamous cells in the nasal cytogram could have explained
      the low effectiveness of local inflammatory treatment in these patients.

PMID- 27024950
TI  - [The elevated level of anti-thyroid antibodies aTPO in chronic spontaneous
      urticaria].
AB  - Diagnosis and treatment of chronic urticaria (CU - Chronic Urticaria) is one of
      the most difficult issues in allergy practice. Studies on the etiopathogenesis of
      chronic urticaria suggest that environmental factors, immune, genetic and
      hormonal are involved in triggering and maintaining the reaction of hives. In
      practice, despite detailed diagnosis is usually not possible to determine the
      real cause of the disease. For this reason, the use of causal treatment for
      patients suffering from chronic urticaria is not possible and supportive
      treatment is often ineffective. 0.1% of the population suffers from chronic
      spontaneous urticaria, which main cause has not been detected. Very often CU
      coexists with autoimmune thyroid dysfunction. Studies confirm higher incidence of
      thyroid antibodies in patients with chronic urticaria than in the general
      population. We analyzed 100 patients who met the criteria for chronic urticaria
      according to the WHO, in Allergology Clinic of the University Hospital
      Jagiellonian University Medical College. According to our study 17.4% of patients
      with chronic spontaneous urticaria occurred elevated titer of anti-TPO
      antibodies. In patients with non-spontaneous type of CU, elevated titer of anti
      TPO antibodies only occurred in 8.3% of patients, and this difference was
      statistically significant p = < 0.003. All the patients had thyroid levels normal
      and there were no clinical symptoms of thyroid dysfunction. Our research
      indicates a link with autoimmune thyroid diseases, especially Hashimoto's
      disease, with a prevalence of CU. It is necessary to conduct further studies to
      confirm the relationship of pathogenic autoimmune thyroid disorders with the
      occurrence of CU, which will help to provide the causal treatment of spontaneous
      CU coexisting with high levels of anti-TPO antibodies in patients with euthyroid
      status.

PMID- 27024951
TI  - [Prevalence of drug allergy claims in school children].
AB  - BACKGROUND: Adverse drug reactions, especially drug hypersensitivity reactions
      (DHR) are common problem, which impacts on prescription choices. In general
      pediatric populations data on the epidemiology of DHRs are scarce compared to in
      patient and adult populations. In the current study, we assess the prevalence of
      parental-reported drug allergy in school children. METHODS: We performed a cross
      sectional survey of a general 6- to 7-yr-old children population from Krakow. The
      life occurrence of drug allergy along with basic data on sensitization to common
      environmental allergens was assessed using a self-administered questionnaire.
      Four thousand eighty questionnaires were collected. RESULTS: The prevalence of
      drug allergy according to answers given by parents was 3.38% (138/4080). The most
      common reported drugs were penicillin and its derivatives (39%), followed by
      sulphonamides (25%), cephalosporins (9%) and non-steroidal anti-inflammatory
      drugs (8%). Sensitization to inhalant allergens, food allergens or haptens was
      not significant risk factor for drug allergy. CONCLUSIONS: The study showed that
      drug allergy claims in children are highly prevalent. Although results are based
      on parental perception, they point out how many patients need complete diagnostic
      work-up to confirm or exclude drug allergy. Otherwise they are treated with
      alternative drugs, which are usually less effective and/or more expensive.

PMID- 27024952
TI  - [Diet with high antioxidant capacity as important factor in primary and secondary
      prevention of asthma].
AB  - In primary and secondary prevention of diseases resulted from antioxidant failure
      and changes towards oxidation processes (autoimmunological/allergic diseases,
      especially asthma) intake of exogenic antioxidants from food is crucial. The aim
      of the study was to estimate diet antioxidant capacity (measured as DWA values)
      among healthy inhabitants of Krakow and assess which food products had the main
      contribution in DAI, in order to give the indications for people suffering from
      bronchial asthma. MATERIAL AND METHODS: The study group consisted of 478 persons:
      350 of healthy inhabitants of Krakow and two specific subpopulations: 48 men with
      high level of physical activity and 80 students from Jagiellonian University and
      Technical Academy. Dietary antioxidant index (DWA) was investigated on the basis
      of food frequency questionnaire (FFQ). In the FFQ 145 food items were classified
      into groups such as fruit and dried fruits, vegetables and vegetable oils,
      sweets, grains and cereal-based products, mixed dishes, fresh herbs, spices and
      beverages. The total antioxidant capacity of food intake was measured using the
      method developed by Benzi. This method exploits the ability of the sample to
      reduce ferricions to ferrousions (FRAP). RESULTS: The total antioxidant capacity
      (measured as DWA) of diet of 225 examined women was higher than calculated from
      253 men and statistically significant (82.7 Mmol/l vs 49.1 Mmol/l). Moreover FRAP
      values of particular groups of food products were higher in case of women than
      men. The highest contribution in total DWA value had fruits and subsequently:
      cereals, juices and beverages. Unfortunately, examined people consumed to low
      amount of vegetables, fresh herbs and spices, which have well-documented
      antioxidant property. CONCLUSIONS: DWA values of healthy individuals presented in
      this study may be treated as a low reference value of antioxidant capacity for
      diets of asthmatic people. Enrichment in natural antioxidants diets of asthmatic
      individuals (mainly men), should become an important element of primary and
      secondary prophylaxis in bronchial asthma.

PMID- 27024953
TI  - [Gluten--mechanisms of intolerance, symptoms and treatment possibilities of IgE
      related allergy for gluten in the light of actual clinical and immunological
      studies].
AB  - Gluten is the product of a chemical bond of wheat prolamin proteins (glia- dins
      and glutenins) in an aqueous me- dium. IgE mediated gluten allergy can be induced
      either by gluten as an in- gredient in foods or wheat prolamines present in the
      air. The aim of the study was clinical analysis of 13 patients, who demonstrated
      elevated levels of gluten specific IgE and identification of the most allergenic
      protein fractions from several samples of wheat using serum of examined subjects.
      Clinical analysis showed the occupational allergy to gluten in the form of
      rhinitis, asthma and airborne dermatistis in 9 subjects, whose symptoms
      disappeared during isolation from occupational exposure despite the use of a
      normal diet. In case of 4 patients with severe forms of chronic urticaria and
      atopic dermatitis, who are also allergic to grass pollen at the same time, the
      introduction of a gluten-free diet resulted in improvement of health conditions.
      The study of wheat protein fractions revealed a significant polymorphism
      dependent on the wheat sample. In the protein fractions, low and high molecular
      glutenin fractions, and alpha, beta, gamma, and omega-gliadins were separated. It
      has been shown that the strongest immunogenic effect causes omega-5 gliadin
      fraction. The removal of this fraction resulted in reduction of skin reactivity
      evaluated by skin prick test in the studied patients.

PMID- 27024955
TI  - [Low salicylate diet in hypersensitivity to nonsteroidal anti-inflammatory
      drugs].
AB  - The article below shows different forms, patomechanisms and diagnostics criteria
      of hypersensitivity to NSAIDs based on available literature as well as up to date
      outlook on implementing low salicylate diet as a treatment.

PMID- 27024954
TI  - [Dietetic interventions in allergic contact dermatitis--when are they
      reasonable?].
AB  - This paper focuses on three questions of dietetic interventions in allergic
      contact dermatitis: 1) in which cases it is justified to suspect that an ingested
      hapten causes allergic reaction, 2) how to verify the causal relationship between
      the hapten and current disease, and 3) in which cases dietary interventions are
      justified? Clinical studies, cases, and reasoning collated in this article
      indicate that contact allergy to food haptens should be suspected when symptoms
      are consistent with the clinical picture of systemic reactivation of allergic
      contact dermatitis or systemic photoallergy. Positive patch test result is not
      sufficient as confirmation of causality--the clinical relevance should be judged
      by means of double-blind placebo-controlled provocation with hapten in question.
      If such challenge appears not feasible, the relevance may be confirmed indirectly
      by the clearance of symptoms after introducing a low-hapten diet with remission
      lasting for at least 4 weeks after withdrawal of pharmacotherapy, and the
      recurrence of symptoms following the return to the old diet. In the majority of
      cases, "nickel-free" or "low nickel" diets are burdensome and with no real
      benefit. Nickel is the fifth most abundant element on Earth and even most
      restrictive diets could reduce nickel load by 50% at best. In the EU alone, 65
      million people are allergic to nickel, while only 1-11% of patients with clinical
      nickel allergy will experience benefits from "nickel-free" diets. Indiscriminate
      introduction of such dietary regimens based merely on positive patch test results
      poses a considerable burden to individuals and society, therefore, it is not
      recommended.

PMID- 27024956
TI  - [IgE is not only a distinctive feature of atopic allergy].
AB  - IgE being commonly accepted as traditional index for allergic diseases is not
      only a characteristic of hypersensitivity disorders. IgE is also involved in the
      pathogenesis of other diseases. This review is giving an overview of IgE
      importance in clinical setting.

PMID- 27024957
TI  - [Immune tolerance mechanisms--brief review].
AB  - The purpose of the immune system is not only to fight off pathogens but also to
      keep a tolerance to self-antigens. In central tolerance, major mechanisms include
      apoptosis (for T cells) and receptor editing (for B cells). Regulatory T cells
      appear to be the most important in peripheral tolerance. Innate immune cells also
      influence the maintenance of immune tolerance. We have provided an overall review
      of all these mechanisms. Successful restoration of the immune tolerance is the
      target of new strategies in autoimmune diseases therapy.

PMID- 27024958
TI  - [Specific allergen immunotherapy in autoimmune diseases].
AB  - The attempts to link allergies with autoimmune diseases have been investigated
      for many years. It is believed that patients with allergies are characterized by
      a lower predisposition to systemic diseases. However, this view is rather poorly
      documented. There are few papers reporting the induction of autoimmune diseases
      in individual patients. However, the question whether an autoimmune disease, even
      subclinical was present before the start of AIT, should also be considered.
      Single studies including large groups of patients with long-term follow-up
      demonstrated a slight but statistically significant reduction in the risk of
      autoimmune diseases in patients with AIT compared to similar patients with
      allergy not subjected to AIT. Obviously, these results require further studies on
      large populations.

PMID- 27024959
TI  - [Usefulness of basophil activation test for the diagnosis of inhaled allergies].
AB  - Allergic diseases are important health problems. Medical history and results of
      additional tests play a crucial role in the diagnosis. Cytometric basophil
      activation test (BAT) is widely evaluated technique in inhaled, food, Hymenoptera
      venom and drugs allergy. The aim of our review is to systematize the available
      knowledge about possibilities of applying BAT, especially in the diagnosis of
      inhaled allergies. Basophil activation markers with proven sensitivity and
      specificity are CD63 and CD203c--each of them has its supporters and opponents
      among researchers. Use of the first one is more popular because of the direct
      relation of its appearance on the cell membrane of basophils with degranulation.
      The usefulness of BAT has been confirmed in the diagnosis of grass pollen, trees
      and house dust mites allergies in children and adults. BAT has a comparable to
      the routinely used tests sensitivity and higher (in most studies evaluated as
      100%) specificity. The disadvantage of BAT that has been observed by some authors
      is "hyperreactivity" of basophils in atopic patients, leading to the appearance
      of false positives results. Basophil activation test seems to have a significant
      advantage over skin tests due to safety and lack of necessary to withdrawal
      antihistamines medications. Future research should focus on the use of BAT in
      diagnostically difficult cases and in monitoring of immunotherapy.

PMID- 27024960
TI  - [Pharmacogenomics of severe drug hypersensitivity reactions--from bench to
      bedside].
AB  - Recent remarkable findings of pharmacogenomics and basic scientific research
      provided insights in the pathogenesis of severe drug hypersensitivity reactions
      such as drug rush with eosinophilia and systemic symptoms (DRESS), abacavir
      hypersensitivity syndrome or blistering reactions (Stevens-Johnson syndrome,
      toxic epidermal necrolysis). There is increasing evidence for the strong
      associations of certain human leukocyte antigen (HLA) alleles with
      hypersensitivity to particular drugs. HLA genes may serve as genomic biomarkers
      of predisposition to severe adverse drug reactions and enable to prevent them. In
      this paper we review essentials and advances in this area.

PMID- 27024961
TI  - [Anaphylaxis as part of a clinical diagnosis of mastocytosi - case
      demonstration].
AB  - Mastocytosis is a heterogeneous group of diseases characterized by excessive
      proliferation and accumulation of mast cells--in one or more organs. The number
      of symptoms and clinical prognosis vary depending on the disease. One of the most
      severe potential outcome of mastocytosis is anaphylactic shock. Early diagnosis
      and identification of triggers enables education and avoidance them. We describe
      the case of a 31-year-old woman with systemic mastocytosis (SM) without skin
      symptoms with multiple anaphylactic reactions, including two severe. Systemic
      mastocytosis was confirmed in bone marrow and genetic studies. We identify
      allergic triggers: latex and cefuroxime and also other non-immunological triggers
      as non-steroidal anti-inflammatory drugs (NSAIDs). The patient never had any
      allergic reaction after Hymenoptera stings. Only one result of serum tryptase was
      elevated. There was a need to determine the safety of antibiotic use and
      anesthetic drugs before cesarean. The moment when the disease was diagnosed and
      triggers were identifie, helped avoid further severe reactions.

PMID- 27024962
TI  - [STAT3 mutation in a child with hyper-IgE syndrome and incomplete clinical
      features].
AB  - We described mutation of STAT3 gene, typical for autosomal dominant
      hiperimmunoglobulin E syndrome (HIES), in a child with recurrent skin abscesses
      and respiratory tract infections without skeletal and connective tissue
      anomalies.

PMID- 27024963
TI  - What about the Children?! Won't Somebody Please Think of the Children!? An
      Advanced Discussion on Florida Informed Consent Law, HIPAA Privacy Rights and
      Dentistry (Part One).

PMID- 27024964
TI  - Board of Dentistry Meets in Lake Mary.

PMID- 27024965
TI  - New Innovations in Dental Licensure Examinations: Patient Centered CIF.

PMID- 27024966
TI  - Exploration of a Failed Attempt to Reinstitute CWF in a Small Mid-Florida Town.

PMID- 27024967
TI  - A Week in the Life ... of an Old Pediatric Dentist.

PMID- 27024968
TI  - Big Cases, Little Patients.

PMID- 27024969
TI  - Diagnostic Discussion. Ameloblastic fibro-odontoma.

PMID- 27024970
TI  - Dentists and Others Volunteer for the Florida Mission of Mercy. Free Dental
      Services for 3,000 of Jacksonville's Neediest.

PMID- 27024971
TI  - Creating a Kid-friendly Waiting Room.

PMID- 27024972
TI  - Total Body Dentistry: The GKAS Revolution.

PMID- 27024973
TI  - Aesthetic Dentistry for Tots and Teens.

PMID- 27024974
TI  - Are You a Dental Superstar?

PMID- 27024975
TI  - Child Abuse and Neglect: As Dental Professionals, How Can We Help and What Are
      Our Responsibilities?

PMID- 27024976
TI  - Support for Women Achieving Cardiovascular Health Through Exercise And Nutrition
      (SWAN) Study Pilot.

PMID- 27024977
TI  - Cutaneous Vasculitis in a Patient with Antiphospholipid Antibody Syndrome.
AB  - Antiphospholipid antibody syndrome (APS) is an acquired thrombophilia, caused by
      autoantibodies to anticardiolipin (aCL), or antibeta 2 glycoprotein I, or the
      presence of lupus anticoagulant (LA) in plasma. It is characterized by recurrent
      venous and/or arterial thrombi and/or pregnancy related morbidities. We present
      the case of a 52-year-old female with long-standing APS, who developed cutaneous
      vasculitis following a common cold. Most of the cutaneous manifestations of APS
      have been found to be thrombotic on histopathology without evidence of
      perivascular inflammation. Vasculitis is usually seen in APS patients with
      coexistent Systemic Lupus Erythematosus (SLE). However, our patient had evidence
      of vasculitis on skin biopsy and did not have SLE. Though rare, this is a disease
      process which must be considered in patients with primary APS which must be
      closely monitored for other vasculitic complications of APS, particularly diffuse
      alveolar hemorrhage.

PMID- 27024978
TI  - A Case of Pneumonia Caused by Pneumocystis Jirovecii and Cryptococcus Neoformans
      in a Patient with HTLV-1 Associated Adult T- Cell Leukemia/Lymphoma: Occam's
      Razor Blunted.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is usually preceded by infection with human
      T-cell lymphotropic virus I (HTLV-I). Patients with ATLL frequently get
      opportunistic infections of the lungs, intestines, and central nervous system.
      Pneumocystis pneumonia is commonly known as an AIDS defining illness. Grocott's
      methenamine silver stain of bronchoalveolar lavage (BAL) samples obtained via
      bronchoscopy remain the gold standard for diagnosis. Pulmonary cryptococcosis is
      seen in patients with T-cell deficiencies and a diagnosis is made by culture of
      sputum, BAL, or occasionally of pleural fluid. We present the second case of
      coinfection with these two organisms in a patient with ATLL who was successfully
      treated with trimethoprim-sulfamethoxazole, corticosteroids, and fluconazole. We
      illustrate the need for high clinical vigilance for seeking out an additional
      diagnosis, especially in immunocompromised patients if they are not improving
      despite receiving appropriate treatment.

PMID- 27024979
TI  - Hyperuricemia and Cardiovascular Disease in Patients with Hypertension.
AB  - BACKGROUND: Little is known about the role of serum uric acid in cardiovascular
      events. We studied the prevalence of hyperuricemia and the association between
      uric acid level and various cardiovascular risk factors. METHODS: This cross
      sectional study was based on a population of patients with hypertension who
      attended a hypertension clinic in a university hospital in Bogota, Colombia.
      Bivariate analysis and multivariate logistic regression models were utilized to
      investigate the relationship between hyperuricemia and cardiovascular risk
      factors. RESULTS: The study population included 444 patients. The overall
      prevalence of hyperuricemia was 28.8%. Male gender (OR 2.3), age (OR 1.03), BMI
      (OR 1.09), triglyceride level (OR 1.005) and low HDL (OR 0.96) were significantly
      associated with hyperuricemia. CONCLUSIONS: Prevalence of hyperuricemia is high
      in patients with hypertension. Serum uric acid is significantly associated with
      parameters of the metabolic syndrome. Hyperuricemia should be acknowledged and
      monitored as a risk factor for cardiovascular disease.

PMID- 27024980
TI  - Lipoid Pneumonia and Sarcoidosis.
AB  - INTRODUCTION: Lipoid pneumonia is a rare, underdiagnosed disorder, and its
      combined presentation with sarcoidosis is even more unusual. METHODS: This paper
      presents a case in which both lipoid pneumonia and sarcoidosis were present, and
      includes the relevant literature review on lipoid pneumonia. RESULTS: Lipoid
      pneumonia may be acute or chronic in its presentation, resulting from exogenous
      or endogenous factors, or classified as idiopathic, with its precise incidence
      unknown. Radiographic changes maybe variable, but typically include lower lobe
      consolidation. Pathologic changes consist of an inflammatory giant cell reaction
      around lipid-related empty vacuoles and giant cell granulomas. Treatment in the
      case of exogenous lipoid pneumonia consists of removal of the offending oil
      ingestion. However, in endogenous lipoid pneumonia, treatment is aimed at the
      underlying cause, as there is no standard treatment. Repeated bronchoalveolar
      lavage, corticosteroids, and surgical resection have been used as therapies. The
      course of the disease is usually not progressive.

PMID- 27024981
TI  - Innovation in Data Abstraction, Education, and Consistent Application of Best
      Practice Guidelines: Experience and Real-World Results from a University Hospital
      in a Cost-Centric Environment.
AB  - BACKGROUND: Adhering to core measures and consistent application of best practice
      guidelines in patients with acute coronary syndromes is challenging for
      hospitals. METHODS: A task force addressed gaps in care and adherence to
      guidelines, and included Emergency Medical Services (EMS) in the decision
      pathway. RESULTS: Previously, our institutional performance on most core metrics
      was in the lower tertile nationally. Task force recommendations and the
      recognition of EMS's role in care produced significant improvement. Seventy-four
      percent of our cardiac catheterization laboratory activations were prehospital
      activations, which resulted in expeditious revascularization. Our composite acute
      myocardial infarction (MI) performance in 2014 was 97.5% for Q1, 97.2% for Q2,
      97.3% for Q3, and 97.3% for Q4. Compliance in most of the individual parameters
      was greater than 95%. CONCLUSION: Identification of systemic gaps, application of
      best practice guidelines, and partnering with EMS improved our core measures and
      patient outcomes without the need for additional resources.

PMID- 27024982
TI  - Considerations for Prescribing Target-Specific Oral Anticoagulants in the Setting
      of Renal Dysfunction or Drug Interactions.

PMID- 27024983
TI  - Growth and Development of Yale's Pediatric Endocrinology Service Reflections on a
      Portrait's Unveiling, May 22, 2015.

PMID- 27024984
TI  - Defining the Disconnects in the Medical Profession.

PMID- 27024986
TI  - LETTERS TO THE EDITOR.

PMID- 27024985
TI  - LETTERS TO THE EDITOR.

PMID- 27024987
TI  - Service Animals Bark less. Wag more.

PMID- 27024988
TI  - "Ch-ch-changes"--David Bowie or, Organized Medicine is Always Going to Be a Bit
      Disorganized.

PMID- 27024989
TI  - Examining the Quality of Life of Farmers with Disabilities: The Ohio AgrAbility
      Study.
AB  - Quality of life is a broad concept that presents a challenge to measure as a
      scientific category. Quality of life encompasses a broad range of variables based
      on an individual's expression of life satisfaction, perceptions, values, feelings
      of subjective well-being, and happiness. This study identified and examined
      factors that influenced the quality of life of Ohio farmers with disabilities who
      were enrolled in the Ohio AgrAbility Program (OAP) (n = 55) and participated in
      this study (60% response rate). A 34-item questionnaire was created. The sample
      of OAP farmers reported stress many days a week, had a negative outlook on life,
      and were less satisfied with their overall quality of life because of their
      health. The OAP participants reported external factors, such as cost of
      equipment, financial pressures, and input costs, as having a negative effect on
      their quality of life. The participants also reported that they were not
      satisfied with the amount of vacation time (60.6%), managing farm work and family
      life (54.6%), overall health (55%), and quality of life (27%). The results showed
      a significant difference between the OAP participants' overall quality of life
      and the following variables: gender, net cash income, outlook on life, health,
      stress, farm work, managing farm and family, social activities, and emotional
      support for farmers with disabilities. The findings of this exploratory study
      allowed farmers to identify factors that they perceived as important to their
      quality of life. Moreover, the results may be helpful for stakeholders to better
      understand the needs of farmers with disabilities and provide appropriate
      educational and other services to enhance their quality of life.

PMID- 27024990
TI  - Summarization of Injury and Fatality Factors Involving Children and Youth in
      Grain Storage and Handling Incidents.
AB  - This article summarizes data gathered on 246 documented cases of children and
      youth under the age of 21 involved in grain storage and handling incidents in
      agricultural workplaces from 1964 to 2013 in the U.S. that have been entered into
      the Purdue Agricultural Confined Space Incident Database. The database is the
      result of ongoing efforts to collect and file information on documented injuries,
      fatalities, and entrapments in all forms of agricultural confined spaces. While
      the frequency of injuries and fatalities involving children and youth in
      agriculture has decreased in recent years, incidents related to agricultural
      confined spaces, especially grain storage and handling facilities, have remained
      largely unchanged during the same period. Approximately 21% of all documented
      incidents involved children and youth (age 20 and younger), and more than 77% of
      all documented incidents were fatal, suggesting an under-reporting of non-fatal
      incidents. Findings indicate that the majority of youth incidents occurred at
      OSHA exempt agricultural worksites. The states reporting the most incidents were
      Indiana, Iowa, Nebraska, Illinois, and Minnesota. Grain transport vehicles
      represented a significant portion of incidents involving children under the age
      of 16. The overwhelming majority of victims were male, and most incidents (50%)
      occurred in June, October, and November. Recommendations include developing
      intervention strategies that target OSHA exempt farms, feedlots, and seed
      processing facilities; preparing engineering design and best practice standards
      that reduce the exposure of children and youth to agricultural confined spaces;
      and developing gender-specific safety resources that incorporate gender-sensitive
      strategies to communicate safety information to the population of young males
      with the greatest risk of exposure to the hazards of agricultural confined
      spaces.

PMID- 27024991
TI  - Summary of Agricultural Confined-Space Related Cases: 1964-2013.
AB  - Since 1977, the Purdue University Agricultural Safety and Health Program has
      managed a database with on going efforts to identify, document, and analyze
      information on injuries and fatalities in all forms of agricultural confined
      spaces, with special attention given to incidents involving grain, forage, and
      manure storage structures and agricultural transport vehicles. The database
      contains over 1650 cases from 1964 to the present and two cases before 1964. The
      average number of cases in the last ten years remains at a high of 63 cases per
      year. Overall, confined-space related cases were documented in 43 states, with
      the most occurring in the Corn Belt region. More than 1000 (62%) of these cases
      were grain-related entrapments; however, in recent years the proportion of grain
      related cases has declined with more aggressive surveillance for all types of
      agricultural confined-space incidents including falls and entanglements inside
      grain storage structures. Grain entrapments represented 49% of all confined space
      cases in 2013 as compared to earlier years when nearly all documented cases were
      grain entrapment related. There has also been a shift in location distribution of
      cases, with the southern states now representing 18% of all recent cases. These
      findings are critical for informing the discussion on developing regulations,
      design standards, and safety programs to reduce the frequency and severity of
      these incidents.

PMID- 27024992
TI  - Rearward Visibility Issues Related to Agricultural Tractors and Self-Propelled
      Machinery: Contributing Factors, Potential Solutions.
AB  - As the size, complexity, and speed of agricultural tractors and self-propelled
      machinery have increased, so have the visibility-related issues, placing
      significant importance on the visual skills, alertness, and reactive abilities of
      the operator. Rearward movement of large agricultural equipment has been
      identified in the literature as causing both fatalities and injuries to
      bystanders who were not visible to the operator and damage to both the machine
      and stationary objects. The addition of monitoring assistance, while not a new
      concept, has advanced significantly, offering agricultural machinery operators
      greater options for increasing their awareness of the area surrounding the
      machine. In this research, we attempt to (1) identify and describe the key
      contributors to agricultural machinery visibility issues, i.e., operator-related
      and machine-related factors, and (2) enumerate and evaluate the potential
      solutions being offered that address these factors. Enhanced operator safety and
      efficiency should result from a better understanding of the efforts to solve the
      visibility problems inherent in large tractors and self-propelled agricultural
      machinery.

PMID- 27024993
TI  - Safety in High School Supervised Agricultural Experiences: Teachers' Training and
      Students' Injury Awareness.
AB  - This research study sought to gather evidence of school-based agriculture
      teachers' hazard perceptions, safety practices, training experiences, and
      awareness of student injuries related to supervised agricultural experience (SAE)
      programs. Teachers agreed that students should follow safety guidelines developed
      by the National Children's Center for Rural and Agricultural Safety and Health
      during SAE work. Approximately 66% (f = 153) of teachers reported having general
      training in first aid, CPR, and AED. Twenty participants (8.6%) indicated having
      no safety certifications or training. Abrasions, lacerations, bites/stings, and
      burns accounted for a majority of the student SAE-related injuries that were
      reported. There were 82 participants (35.5%) who stated that no injuries had been
      reported or they were not aware of any injuries that occurred. The majority of
      teachers (66%) had received some form offirst aid or first response training, but
      fewer teachers had received safety training for ATVs (f = 25, 10.8%), tractors (f
      = 48, 20.7%), and livestock (f = 39, 16.8%). Results indicated a disparity
      between required safe work habits and the types of hazardous tasks students
      should be allowed to complete alone while participating in SAE activities. It
      appears most responding teachers in this study agreed to allow students to
      operate equipment and machinery alone. Recommendations for teachers include
      attending professional development training specific to SAE safety and keeping
      records of any risk assessments conducted during SAE supervision. Further
      development of best practices for SAE supervision and safety are needed to assist
      agricultural education professionals in protecting and shaping our future leaders
      in agriculture.

PMID- 27024994
TI  - Characteristics of Fatal Agricultural Injuries by Production Type.
AB  - Although agriculture is recognized as a hazardous industry, it is unclear how
      fatal agricultural injuries differ by production type. The purpose of this study
      was to characterize fatal occupational injuries in agriculture, comparing crop
      and animal production, and determine which risk factors are specifically
      associated with each production type. A cross-sectional study was conducted among
      crop and animal pro ducers using data from the Census of Fatal Occupational
      Injuries in the Midwest region from 2005 to 2012. Rates offatal injury by
      production type were estimated. The frequency of fatal injury in each production
      type was also reported by demographic and injury characteristics. Finally, a
      logistic regression was performed to determine whether age, gender, injury
      timing, or injury event/exposure type were associated with crop or animal
      production. A total of 1,858 fatal agriculture-related injuries were identified,
      with 1,341 in crop production and 517 in animal production. The estimated rate of
      fatal injury was higher in crop production than in animal production (15.9 vs.
      10.8 per 100,000 workers). Fatal injuries among young and elderly agricultural
      workers were significantly associated with crop production compared to animal
      production. Animal assaults, falls, and exposure to harmful substances or
      environments were significantly associated with animal production. Fatal
      agricultural injury is more common in crop production. However, the
      characteristics and risk factors of fatal injuries differ by production type.
      Intervention strategies may be guided by considering the production-specflc risk
      factors.

PMID- 27024995
TI  - Ahoy, Mates! Changes Ahead!

PMID- 27024996
TI  - Sustainability of Innovations. Part II: Exemplar of Addressing Sustainability
      Factors in the Development and Implementation of an Evidenced-Based Practice
      Improvement Project.

PMID- 27024997
TI  - Complex Psychological Trauma and Self-Dysregulation: A Theory Synthesis for
      Nursing.
AB  - Complex psychological trauma is a phenomenon resulting from severe interpersonal
      trauma that can negatively affect how individuals experience health care.
      However, few theories conceptualizing complex trauma exist, and it has received
      only limited attention in the nursing literature. The purpose of this theory
      synthesis was to organize two theories of (a) self-regulation and (b) self
      dysregulation following complex psychological trauma into a single conceptual
      framework for use in nursing practice. This article used the theory synthesis
      approach described by Walker and Avant. The theory has potential to advance
      nursing science by helping nurses and other health professionals understand how
      trauma can alter self-regulatory processes and result in unique challenges in
      care delivery. It also has potential to prevent retraumatization of trauma
      survivors at the hands of health care providers.

PMID- 27024998
TI  - Shared Decision-Making Models Acknowledging an Interprofessional Approach: A
      Theory Analysis to Inform Nursing Practice.
AB  - Patient engagement in collaboration with health professionals is essential to
      deliver quality health care. A shared decision-making (SDM) approach requires
      that patients are involved in decisions regarding their health. SDM is expanding
      from the patient-physician dyad to incorporate an interprofessional perspective.
      Conceptual models can be used to better understand theoretical underpinnings for
      application in clinical practice. The aim of this article was to conduct a theory
      analysis of conceptual models using an interprofessional approach to SDM and
      discuss each model's relevance to nursing practice. Walker and Avant's theory
      analysis approach was used. Three conceptual models were eligible. For all
      models, the decision-making process was considered iterative. The development
      process was described for 1 model. All models were logical, parsimonious, and
      generalizable. One was supported by empirical testing. No model described how
      partnerships are enacted to achieve interprofessional SDM. Also, there was
      limited articulation as to how nurses' roles and contributions differ from other
      team members. This theory analysis highlights the need for a model that explains
      how partnerships among interprofessional team members are enacted to better
      understand the operationalization of interprofessional SDM. Implications for
      nursing practice at all system levels are offered and supported by the 3 models.

PMID- 27024999
TI  - Concept Analysis: Music Therapy.
AB  - Down through the ages, music has been universally valued for its therapeutic
      properties based on the psychological and physiological responses in humans.
      However, the underlying mechanisms of the psychological and physiological
      responses to music have been poorly identified and defined. Without
      clarification, a concept can be misused, thereby diminishing its importance for
      application to nursing research and practice. The purpose of this article was for
      the clarification of the concept of music therapy based on Walker and Avant's
      concept analysis strategy. A review of recent nursing and health-related
      literature covering the years 2007-2014 was performed on the concepts of music,
      music therapy, preferred music, and individualized music. As a result of the
      search, the attributes, antecedents, and consequences of music therapy were
      identified, defined, and used to develop a conceptual model of music therapy. The
      conceptual model of music therapy provides direction for developing music
      interventions for nursing research and practice to be tested in various settings
      to improve various patient outcomes. Based on Walker and Avant's concept analysis
      strategy, model and contrary cases are included. Implications for future nursing
      research and practice to use the psychological and physiological responses to
      music therapy are discussed.

PMID- 27025000
TI  - Psychometric Properties of the Arabic Version of the Summary of Diabetes Self
      Care Activities Instrument.
AB  - Translation of instruments needs to ensure equivalence between the source and the
      target language to establish the psychometric properties of the translated
      version. The purpose of this study was to examine the psychometric properties of
      the Arabic version of the Summary of Diabetes Self-Care Activities (SDSCA)
      instrument. The 12-item English version of the SDSCA was translated into Arabic
      using back translation on a sample of 140 Lebanese participants with Type 2
      diabetes. Construct validity was measured using exploratory factor analysis with
      varimax rotation. Multitrait scaling analysis was used to test for item
      convergent and discriminant validity based on item-scale correlations. Conceptual
      and content validity were examined by an expert panel in diabetes. Internal
      consistency reliability R was assessed using interitem correlations. The average
      interitem correlation for the four subscales ranged between--.05 for Diet and .66
      for Glucose Testing. Factor analysis identified four factors which accounted for
      60% of the variance. The preliminary results of Summary of Diabetes Self-Care
      Activities-Arabic Version (SDSCA-Ar) are comparable to the psychometric
      properties the original SDSCA. SDSCA-Ar is a valid measure of diabetes self-care
      in Lebanese patients with diabetes.

PMID- 27025001
TI  - Educational Video Intervention Effects on Periprocedural Anxiety Levels Among
      Cardiac Catheterization Patients: A Randomized Clinical Trial.
AB  - PURPOSE: To explore the effectiveness of an educational video intervention in
      lowering periprocedural anxiety among Jordanian patients hospitalized for cardiac
      catheterization (CATH). There are many potential reasons of anxiety related to
      CATH including involvement of the heart and the actual test procedure. METHODS: A
      randomized controlled trial took place in a specialized heart institute in
      Jordan. The sample size was 186 patients who had undergone CATH procedure.
      Patients anxiety levels were measured by physiological parameters of anxiety
      (blood pressure, heart rate, and respiratory rate) and by the Spielberger State
      Anxiety Inventory (SAI). RESULTS: After video education, there was a significant
      difference in periprocedural perceived anxiety between the groups: preprocedural
      anxiety levels (M = 39.03, SD = 5.70) for the experimental group versus (M =
      49.34, SD = 6.00) for the control, p < .001, and postprocedural perceived anxiety
      for the experimental group (M = 29.18, SD = 5.42) versus (M = 41.73, SD = 5.41)
      for the control. CONCLUSION: Providing an educational video intervention about
      CATH may effectively decrease periprocedural anxiety levels.

PMID- 27025002
TI  - [Application of DNA microarray analysis pipeline established in nutrigenomics to
      other research field].

PMID- 27025003
TI  - [Construction of 1070 Whole-genome Japanese Reference Panel and Bioinformatics].

PMID- 27025004
TI  - [Jananese Multi Omics Reference Panel].

PMID- 27025006
TI  - [Progress of Japanese Omics Reference Panels in Iwate Tohoku Medical Megabank
      Project].

PMID- 27025005
TI  - [Extensive analysis of protein phosphorylation: An example of transcription
      factor Bach2].

PMID- 27025007
TI  - [Rice breeding based on whole genome sequencing using next-generation sequencer].

PMID- 27025008
TI  - [Bridging -omics and reductionist approaches through signaling network modeling
      at system levels].

PMID- 27025009
TI  - [Towards understanding the mechanisms of negligible senescence and cancer
      resistance: Insights from naked mole rat and long-lived species].

PMID- 27025010
TI  - [Versatile in vivo functions of the small GTPase Arf6].

PMID- 27025011
TI  - [Secreted factor, FGF21, regulates diverse biological processes].

PMID- 27025012
TI  - [Plant sphingolipids: recent advances in the analyses of their structural
      diversity and metabolic pathway].

PMID- 27025013
TI  - [Functions of Reelin in cortical neuron migration].

PMID- 27025014
TI  - [Approach for Visualization of Sec Translocon Machinery].

PMID- 27025015
TI  - [Genome editing in mouse with CRISPR/Cas system].

PMID- 27025016
TI  - [Role of IRF transcription factor family in regulating reactive phenotype of
      microglia].

PMID- 27025017
TI  - [Clarification of astrocytic function through Ca2+ imaging].

PMID- 27025018
TI  - [Fine-tuning of translation initiation by RNA binding proteins].

PMID- 27025019
TI  - [Yip1A, a novel host factor required for the intracellular replication of
      Brucella abortus].

PMID- 27025020
TI  - [SIMULTANT OPERATIONS FOR BILIARY CALCULOUS DISEASE AS A METHOD OF PREVENTION OF
      POSTCHOLECYSTECTOMY SYNDROME].
AB  - Abstract Own experience of treatment of patients for biliary calculous disease,
      coexistent with other abdominal and retroperitoneal organs diseases, was
      analyzed. The rate of postcholecystectomy syndrome (PCHES) occurrence in such
      patients was determined, the impact of simultant operative interventions using
      laparoscopic and laparotomic accesses on the rate of the PCHES occurrence was
      established. The elaborated diagnostic-treatment algorithm with application of
      measures, directed on the PCHES prophylaxis, was elaborated. There was
      established, that performance of simultant operations in accordance to strict
      indications secures a trustworthy reduction of the PCHES occurrence rate.

PMID- 27025021
TI  - [APPLICATION OF MICROJEJUNOSTOMY IN SURGICAL PRACTICE].
AB  - Microjejunostomy was performed to 12 patients in surgical department in 2013
      2014yrs with the objective of decompression of initial portions of a small bowel
      and nutritivEesupport achievement. While performing primary operative
      intervention decompressiornwas applied in 4 patients, and while relaparotomy --n
      8. Application of method of asmall bowel drainage have provided its adequate
      decompression and was not accom pnied by additional trauma of the structures
      drained. This method may constitutEealternative for duodenostomy.

PMID- 27025022
TI  - [INFLUENCE TIMING OF THE START OF ENTERAL NUTRITION ON THE IMMEDIATE RESULTS OF
      SURGICAL TREATMENT OF COLON CANCER].
AB  - Results of treatment of 215 patients with colon cancer (CC), whom performed at
      the clinic radical or palliative intervention were analyzed. In 100 patients
      (control group) enteral nutrition (EN) began after the restoration of the
      alimentary canal functions; in 115 (main group)--no later than 12 hours after
      surgery. For the EN in all patients used a balanced liquid mixture "Frezubin"
      manufactured by Fresenius Kabi GmbH (Germany). It is proved that early EN is a
      safe and effective method in the program of the accelerated rehabilitation of
      patients after surgery for CC.

PMID- 27025023
TI  - [PREDICTORS OF PERITONEAL CARCINOMATOSIS IN PATIENTS WITH COLORECTAL CANCER].
AB  - The risk factors for peritoneal carcinomatosis (PC) occurrence after radical
      surgical treatment of patients, suffering colorectal cancer, were analyzed.
      Probability of the disease recurrence occurrence have depended upon a patient's
      age, the invasion depth of primary tumor, its histological type and
      differentiation degree. Determination of independent predictors gives possibility
      to prognosticate the PC individually and to diagnose it early.

PMID- 27025024
TI  - [MICROBIAL LANDSCAPE OF BILE IN PATIENTS WITH AN ACUTE PURULENT CHOLANGITIS].
AB  - Bacteriological analysis was conducted in 136 patients with an acute purulent
      cholangitis (APCH). The APCH causes were: choledocholithiasis--in 40 (29.9%)
      patients, coexistence of a common biliary duct stricture and choledocholithiasis-
      in 39 (28.7%), compression of external biliary ducts by the oedematous pancreatic
      head in secondary pancreatitis--in 15 (11%), pericholedocheal lymphadenitis--in 3
      (2.2%).

PMID- 27025025
TI  - [MINIINVASIVE AND ENDOSCOPIC METHODS OF TREATMENT OF POSTNECROTIC PANCREATIC
      PSEUDOCYSTS].
AB  - The results of treatment of 89 patients, suffering an acute accumulations of
      liquid (AAL)and postnecrotic pancreatic pseudocysts (PPP) on background of an
      acute necroticpancreatitis, were studied. The volume of AAL and PPP have
      constituted from 65 to2750 cm3. The alcohol abuse and alimentary factor--in 63
      (70.7%) patients, biliary calculous disease--in 21 (23.6%), and other--in 5
      (5.7%) have constituted the diseasecauses. In 33 (37%) patients miniinvasive
      interventions were performed, and in the rest--the endoscopic. Miniinvasive and
      endoscopic interventions for PPP were done in 4-8 weeks from the disease
      beginning.

PMID- 27025026
TI  - [OPTIMIZATION OF THE TREATMENT TACTICS IN BRAIN ABSCESS, USING THE PUNCTURE
      STEREOTAXIC ASPIRATION].
AB  - There was analyzed the application efficacy of stereotaxic aspiration of the
      brain abscess (BA) content, localized in a deep and functionally significant
      parts of the brain, in 12 patients--with supratentorial BA. Stereotaxic
      interventions were performed, using stereotaxic systems CRW Radionics (USA) and
      the security program for calculation of coordynates StereoFusion, StereoPlan
      (Radionics), Fraime Link (Medtronic, USA). Postoperative observation period have
      lasted from 1 to 36 mo, (14 +/- 3.6) mo at average. lntraoperatively in 11
      (91.7%) patients a purulent content of BA was evacuated, and in 1 (8.3%)--a BA
      was diagnosed in the encephalitis stage. Stereotaxic aspiration is an effective
      and secure method of surgical treatment of BA. It may constitute an alternative
      to open surgical excision of BA due to lesser invasiveness and possibility of the
      neurological complications occurrence.

PMID- 27025027
TI  - [INTERVENTIONAL AND SURGICAL TREATMENT OF THE ANGINA PECTORIS RECURRENCE AFTER
      CORONARY SHUNTING OPERATION].
AB  - There were examined 134 patients, in whom in the clinic in 2005-2014 yrs a
      coronary shunting operation was performed. In patients with the angina pectoris
      recurrence a reoperation is indicated. The data of repeated
      coronaroventriculography and shuntography were analyzed. Efficacy of the surgical
      and interventional methods application in the patients was proved.

PMID- 27025028
TI  - [BENIGN TUMORS OF MEDIASTINUM: CLINIC, DIAGNOSIS, SURGICAL TREATMENT].
AB  - Results of surgical treatment of 18 patients in a thoracic surgery clinic for
      benign tumors of mediastinum are presented. The symptoms of benign tumors,
      efficacy of application of welding technologies in operative intervention were
      analyzed.

PMID- 27025029
TI  - [PECULIARITIES OF TRACHEAL EXTUBATION IN PATIENTS, OPERATED ON FOR PHLEGMON OF
      THE NECK].
AB  - The results of anesthesiological support of 75 patients, operated on for phlegmon
      of the neck, were presented. An acute respiratory insufficiency rate, occurring
      after tracheal extubation, necessitating an emergent tracheostomy conduction,
      have constituted 13.5%. Preliminary conduction of diagnostic direct laryngoscopy
      and the "air source" test permits to predict a noncomplicated tracheal extubation
      trustworthy. Tracheal extubation after the operation must be conducted not
      earlier than in 10 - 72 h.

PMID- 27025030
TI  - [FACTORS OF PROGNOSIS IN PATIENTS WITH EARLY CANCER OF MAMMARY GLAND].
AB  - A survival indices in patients with early mammary gland cancer of a ductal
      infiltrating histology stage T1-2N0M0, who were treated in accordance to actual
      standards, differ significantly, what witnesses the necessity for searching of
      additional prognostic criteria. The investigation objective was to study the
      impact of independent and interrelated clinical, morphological and biochemical
      factors of prognosis on the survival indices in patients with mammary gland
      cancer stage T1-2N0M0 in conditions of local and systemic treatment.

PMID- 27025031
TI  - [NEOADJUVANT TARGET THERAPY IN A RENAL-CELL CANCER].
AB  - There were observed 30 patients (32 tumors), to whom preoperatively for renal
      cell cancer (ROC) a neoadjuvant target therapy (NATTH) was conducted. In 19
      (66.7%) of them a pazopanib (800 mg per os once a day through 2 mo) was applied,
      and in 10 (33.3%)--sunitinib (50 mg per os once a day through 28 days, the gap-
      14 days, repeated course--28 days). The indications for the NATTH conduction
      were: in 7 (21.9%) patients--a locally--spread RCC with the objective to localize
      a tumor and to search a further possibility of radical surgical intervention
      performance, and in 25 (78.1%)--the tumor reduction and searching possibility of
      the organpreserving treatment conduction. The NATTH conduction in the patients,
      suffering RCC, have guaranteed a primary pathological focus reduction in 90% of
      observations, and a partial regression in accordance to the RECIST criteria--in
      28.1%. A tumor reduction by (22.9 +/- 17.8)% at average have permitted to perform
      a renal resection in 75% of observations, concerning localized RCC, when
      indication of preservation of enough functioning renal parenchyma was secured.

PMID- 27025032
TI  - [PREVENTION OF THE BONES METASTASES OCCURRENCE IN THE PATIENTS WITH RENAL-CELL
      CANCER].
AB  - Diagnostic significance of estimation of the tartratresistent acid phosphatase
      (bone TRAP--5b) activity was studied for prognosis of occurrence of metastases in
      bones (MB) in patients with a renal-cell cancer (RCC). The risk of the MB
      occurrence was determined in patients after surgical treatment. A skeleton
      affection rate in patients, to whom zolendronic acid was prescribed, was
      trustworthy bigger, than such while conduction of treatment. So, application of
      bisphosphonates is recommended, in particular--zolendronic acid in dosage 4 mg
      every month under control of the bone TRAP--5b activity with objective of
      prophylaxis of the MB occurrence in patients, suffering RCC. But, we recommend
      for the MB diagnosis the method of determination of this marker activity as
      additional one while examining patients together with standard methods, including
      osteoscintigraphy, computer tomography.

PMID- 27025033
TI  - [THE PRINCIPLES OF ORGANIZATION AND TREATMENT FOR SORTING OF WOUNDED PERSONS WITH
      A COMBAT SURGICAL TRAUMA OF EXTREMITIES ON THE IV LEVEL OF THE MEDICAL CARE
      PROVISION].
AB  - Experience of medical sorting of 434 injured persons with a gun-shot woundings of
      extremities in 2014-2015 yrs is adduced. The principles of organization and
      treatment for medical sorting of wounded persons were elaborated. Prognostic
      intrahospital, diagnostic and evacuation--transport sorting was introduced in
      wounded persons in the IV level hospital, concerning severity of traumatic shock
      and prognosis of their survival.

PMID- 27025034
TI  - [PROGNOSIS OF INFECTIVE COMPLICATIONS OF THE GUN-SHOT WOUNDS OF SOFT TISSUES].
AB  - The method of prognostication of infectious complications in a gun-shot wound was
      elaborated, using the methods of logistic regression analysis.

PMID- 27025035
TI  - [IMPROVEMENT OF A "DELAY" METHOD WHILE PREPARATION OF FLAPS FOR PLASTIC
      OPERATION].
AB  - The improved method "delay", providing preservation of a small bridge of tissues
      near the flap tip, which are compressed with ligature or the strip of the glove's
      rubber during 7 - 12 days, was proposed for prevention of critical ischemia in
      the flap tissues. It permits to avoid the flap tissues critical ischemia up to
      the moment of the vascular net and blood flow enhancement while a compelled
      division of the flap in conditions of the damaged tissues or the cases of the
      flap area bigger than the area of the nutrient vessels basin. The improved method
      "delay" was applied successfully while the flaps preparation, formatted on
      temporary and constant nutritive pedicle, to plastic operation in 7 injured
      persons, suffering trauma of extremities.

PMID- 27025037
TI  - [LIPOFILING. MODERN VIEWS].

PMID- 27025036
TI  - [CLINIC-EXPERIMENTAL SUBSTANTIATION OF OZONOTHERAPY APPLICATION IN THE TREATMENT
      OF PURULENT CHOLANGITIS AND OBTURATION JAUNDICE].
AB  - Efficacy of the ozonotherapy application as an important component of complex
      treatment in purulent cholangitis (PCH) was studied. In choledocholithiasis
      (without infectioning of bile) ozonotherapy may be prescribed as additional
      component at complex treatment. In PCH ozonotherapy application have promoted the
      improvement of laboratory indices in 6.6 times, comparing with such, occurring
      after basic therapy.

PMID- 27025038
TI  - [OPERATIVE TREATMENT OF A LATE CICATRICIAL STRICTURE OF ESOPHAGOCOLOANASTOMOSIS
      AFTER PERFORMANCE OF ESOPHAGOPLASTY WITH A LARGE BOWEL SEGMENT].

PMID- 27025039
TI  - [HYDROGEN SULFIDE DONOR, NAHS, RECOVERS CONSTITUTIVE NO SYNTHESIS AND ENDOTHELIUM
      DEPENDENT RELAXATION OF ISOLATED AORTA IN OLD RATS].
AB  - The objective of this study was to show the effect of H2S donor, NaHS on the
      endothelium-dependent vasorelaxation, free radical state and cNOS uncoupling in
      old rats. In the aorta of old rats a combined oxidative and nitrosative stress
      develops that leads to cNOS uncoupling and decreased constitutive synthesis of
      the NO. That biochemical changes correlate with lowering of the endothelium
      dependent relaxation of aortic smooth muscles (7.5 +/- 1.4%, compared with 64.9
      +/- 3.5% in adults). It was found that, due to the combined inhibition of
      oxidative and nitrosative stress, NaHS restores constitutive de novo synthesis of
      NO by restoring cNOS coupling. Additionally, NaHS improves endothelium-dependent
      vasorelaxation by increasing (by 6.5 times) Ach-induced relaxation of aortic
      smooth muscles.

PMID- 27025040
TI  - [EFFECT OF NEONATAL SEIZURES ON THE SYNAPTIC PLASTICITY OF RAT SOMATOSENSORY
      CORTEX].
AB  - Using an experimental model of neonatal recurrent seizures we investigated the
      influence of epileptic seizures in the various forms of synaptic plasticity in
      neurons of the somatosensory cortex. We found that early seizures do not affect
      the post-tetanic potentiation of the amplitude of the postsynaptic potentials and
      the depression of postsynaptic potentials during high-frequency stimulation.
      However they result in the chronic increase of the long-term potentiation of
      synaptic transmission. These changes of synaptic plasticity may affect the
      processing of the sensory information in patients with a history of recurrent
      seizures during early development.

PMID- 27025041
TI  - [CA2+ ACCUMULATION IN ISOLATED RAT HEART MITOCHONDRIA UNDER MAINTENANCE OF
      MITOCHONDRIAL POTENTIAL].
AB  - It is known that mitochondria can accumulate calcium, which regulates energy
      metabolism and cell death. About 90% of energy of cardiomyocytes is synthesized
      in mitochondria. Heart cells are also affected by the rapid changes in the Ca2+
      concentration in the cytoplasm. Therefore, mitochondrial Ca2+-accumulation
      ability is crucial. The aim of our work was to study the accumulation of Ca2+ in
      isolated rat heart mitochondria in the presence of mitochondrial potential and
      different extramitochondrial Ca2+ concentrations. Isolated organelles were loaded
      with fluorescent dye Fluo-4 AM (2.5 MUmol/l) at a temperature of 26 degrees C for
      30 min. It has been revealed that under these conditions high mitochondrial
      potential was maintained sufficiently, which is necessary for the functioning of
      the calcium transporting system in organelles. We established that mitochondria
      have a limited ability to store ionized calcium, as addition of Ca2+ ion in
      concentrations of 10, 20, 50 umol/l ensures a certain level of accumulation in
      organelles with further fluorescent signal growth cessation. Addition of 100
      umol/Ca2+ to isolated mitochondria resulted in a significant increase in
      fluorescence intensity (46% in the fifth minute, compared to the fluorescence
      when 20 umol/l Ca2+ was added) and likely to activation of cation release. It was
      shown that ruthenium red (10-5 mol/l), an inhibitor of Ca2+-uniporter, prevented
      accumulation of calcium ions in organelles by 89%, in the presence of 100 umol/
      Ca2+. It was clearly seen that heart mitochondria require Mg2+-ATP complex (3
      mmol/l) to accumulate Ca2+, likely to maintain the inner membrane potential,
      activity of Ca2+ uniporter and energetic processes in organelles. Thus, the
      process of Ca2+ accumulation in rat heart mitochondria requires the maintenance
      of mitochondrial potential, activity of Ca2+-uniporter, depends on
      extramitochondrial Ca2+ concentration and presence of Mg2+-ATP complex.

PMID- 27025042
TI  - [THE EFFECTS OF LYS-PLASMINOGEN ON HUMAN PLATELET SECRETION].
AB  - The effects of Lys-plasminoge on platelet alpha-granule secretion were studied.
      The level of P-selectin exposed on the surface of plasma membranes of washed
      human platelets was measured by flow cytometry as a market of alpha-granule
      secretion. It was shown that Lys-plasminogen facilitates partial release of alpha
      granules, but impedes thrombin-induced platelet exocytosis. It is suggested that
      Lys-plasminogen may affect platelet secretion rather through interaction of its
      non-catalytic (kringle) domains with membrane receptors than due to contaminating
      plasmin activity. In contrast to Lys-form, native proenzyme (Glu-plasminogen) had
      no effects on alpha-granule releasing. Here, we provide the first experimental
      demonstration that Lys-form of plasminogen is able to modulate platelet alpha
      granule secretion, and this effect can be considered as one of the plausible
      mechanisms of its anti-aggregating activity.

PMID- 27025043
TI  - [ENERGETIC AND ANTIOXIDANT STATUS OF RAT LIVER MITOCHONDRIA DURING HYPOXIA
      REOXYGENATION OF DIFFERENT DURATION].
AB  - Dynamics of changes in activity and protein expression of antiradical (MnSOD),
      glutathione-dependent (glutathione peroxidase, glutathione reductase) and NADP+
      generated (isocitrate dehydrogenase) enzymes as well as in the energy metabolism
      indeces in rat liver mitochondria under hypoxia- reoxygenation of different
      duration (1, 3, 7 14 days) were studied. Prolonged hypoxia-reoxygenation was
      characterized by phase changes of the corticosterone concentration in rat blood,
      which corresponded to the changes in energy metabolism as well as in pro- and
      antioxidant balance in rat liver mitochondria. It has been shown that short-term
      (1 day) hypoxia-reoxygenation (5% O2 in the gas mixture) led to an increase in
      the blood corticosterone concentration and a significant activation of oxidative
      processes and energy metabolism in rat liver mitochondria, the intensity of which
      was reduced to 3rd day. Long- term hypoxia--reoxygenation (7-14th days) led to
      the gradual depletion of the organism adaptive capabilities, as evidenced by a
      significant decline in the blood corticosterone concentration, an increase in the
      content of secondary products of lipid peroxidation, an imbalance in pro- and
      antioxidant reactions and reduction of energy capacity in liver cells
      mitochondria. It has been shown that the glutathione peroxidase protein
      expression and enzymatic activity increased constantly during the whole
      experimental period and correlated positively with the level of H2O2. The amount
      of Mn-SOD protein as well as it's enzymatic activity was lower in the first seven
      days of experiment, and it was increased in consequent days up to the control
      level on 14thday. Increased activity of glutathione peroxidase, glutathione
      reductase and NADP++dependent isocitrate dehydrogenase during prolonged hypoxia -
      eoxygenation indicates that glutathione- and NADPH-generating enzymes, were
      actively involved in the antioxidant protect.

PMID- 27025044
TI  - [NADPH-DIAPHORASE REACTIVITY IN THE VENTRAL HORN OF THE FELINE SPINAL CORD DURING
      ACUTE MUSCLE INFLAMMATION].
AB  - The aim of this research was to reveal the changes in the NADPH-d reactivity in
      the lumbal spinal cord (L6/L7) of cats with unilateral acute myositis of the mm.
      gastrocnemius-soleus after intramuscular injections of carrageenan. The effect of
      unilateral muscle inflammation was expressed in a significant increase in the
      number of NADPH-d-reactive neurons in ipsilateral and contralateral intermediate
      (lamina VII; 17.62 +/- 2.7 and 20.67 +/- 13.3) and medial (lamina VIII; 7.3 +/-
      1.9 and 6.0 +/- 2.1 respectively) zones of the ventral horns. However, a clear
      decline of the reactive cells was recorded on the ipsilateral side within the
      area around the central canal (lamina X). An increase in the NADPH-d reactivity
      within the ventral horns on both sides on the spinal cord and the induction of
      such reactivity (contralaterally) in large multipolar neurons localized in the
      dorsal part of the intermediate zone were revealed in cats with unilateral acute
      muscle inflammation. It is hypothesized, that during acute myositis, plastic
      changes in different layers of the dorsal and ventral horns activate the
      processes of disinhibition due to an increase in the number of NOS
      containing/NADPH-d-reactive neurons in the spinal gray matter.

PMID- 27025045
TI  - [TISSUE BLOOD FLOW IN THE DIGESTIVE ORGANS OF RATS WITH ACUTE PANCREATITIS AFTER
      CORVITIN ADMINISTRATION].
AB  - We have investigated the action of quercetin (in a modified form--Corvitin, BCPP,
      Ukraine) on the rate of blood flow in the pancreas, liver and gastric mucosa of
      rats with acute pancreatitis (AP) caused by administration of L-arginine. The
      rate of blood flow was measured by hydrogen clearance method with electrochemical
      his generation using Polarographs Lr-9 (Czech Republic). During the first 10 days
      after modelling of AP in these organs it was observed a gradual decrease compared
      to the intact animals in the rate of blood flow by 42% (P < 0.01) in the
      pancreas; by 61% (P < 0.001) in the liver and by 64% (P < 0.001) in the gastric
      mucosa, i.e., the most significant changes occurred in the gastric mucosa, the
      least--in the tissue of the pancreas. Compared with the control group of animals
      with modelling acute pancreatitis which during 20 days was administered only
      saline, application of Corvitin (5 mg/kg, 1 time per day from 11 to 20 days of
      experiment) in varying degrees promoted to the recovery of the rate of blood flow
      in all investigated organs: in the pancreas--fully, in the liver--almost entirely
      and in the gastric mucosa--only partially. Thus, based on obtained results
      Corvitin can be recommended for partial or complete correction of blood flow
      disturbances, which arise in the pancreas and other organs of the digestive
      system in AP. Corvitin can improve the functional state of these organs in the
      early stages of the disease and accelerate the full restoration of their
      functions.

PMID- 27025046
TI  - [FUNCTIONAL ACTIVITY OF EHRLICH CARCINOMA CELLS AFTER TREATMENT WITH HYBRID
      NANOCOMPLEXES CONTAINING ORTHOVANADATES OF RARE-EARTH ELEMENTS, CHOLESTEROL AND
      LUMINESCENT DYE].
AB  - Tumor development is the consequence of expanding the population of low
      differentiated cells with unlimited self-maintenance potential, i.e. cancer stem
      cells (CSCs). Application of new forms of nanocomposites capable of binding to
      CSCs and inducing the tumor destruction is perspective direction for treating
      this pathology. There have been developed the methods of obtaining hybrid
      nanocomplexes containing rare-earth orthovanadates GdYVO4:Eu3+, cholesterol and
      luminescent dye Dil. By immune fluorescence method using monoclonal antibodies to
      CD44, CD24, CD117 and Sca-1 markers there has been established the change in the
      ratio of tumor progenitors of various differentiation levels in a general pool of
      Ehrlich carcinoma (EC) after treatment with hybrid nanocomplexes. Essential
      reduction in the concentration of the most tumorogenic CD44high cells with
      simultaneous rise in the number of CD117+-cells resulted in an increased index of
      CD44high/CD117+ ratio. It has been demonstrated that application of hybrid
      nanocomplexes suppressed the tumor growth almost by 80%. The value of cooperative
      interactions of the cells with different phenotype signs in tumor sites has been
      proved. The index of CD44high/CD117+ ratio can be used as one of diagnostic and
      prognostic parameters of development and inactivation rate of tumor process when
      using different types of anti-tumor therapy.

PMID- 27025047
TI  - [DETERMINATION OF THE OPTIMAL SAFE MODE OF PHYSICAL ACTIVITY FOR THE MILITARY
      SERVANTS UNDER CONDITIONS CLOSE TO FIGHTING].
AB  - The paper presents the results of research, allowing to establish the need for
      and feasibility of an integrated method to determine the most effective but at
      the same time safe modes of load to the body troops. We found that despite the
      rather promising application of our proposed mode of load of high intensity (Ra =
      0.71) to increase the level of physical military training as soon as possible in
      time of peace (with a minimum set of combat equipment), problematic issue is that
      in most cases there is a complete-mismatch achieved in the degree of physical
      development of the body of military requirements and the challenges posed in
      terms of direct hostilities. Using the integral method developed by us we
      determine the safest modes of exercise for the military servants to optimize the
      most appropriate parameters of volume and intensity of the load, and speed up the
      adaptive changes in their body to enhance maximum performance at this stage of
      preparation.

PMID- 27025048
TI  - [NET WATER TRANSPORT VIA RAT COLON EPITELIUM UNDER THE EXPERIMENTAL DYSBIOSIS].
AB  - The aim of the present study was to investigate the effect of cephalosporin
      antibiotic ceftriaxone (50 mg/kg, i/m) and mac- rolide antibiotic azithromycin
      (15 mg/kg, per.os.) on net water transport across rat colonic epithelium. Study
      was done on male Wistar rats (180-250 g). Azithromycin or ceftriaxone was
      injected daily for 5 days. Net water transport was evaluated on the 6th day by
      isolated colonic loop perfusion technique in vivo on anaesthetized rats.
      Treatment with azithromycin increased 2,4-fold the absorption of water, while
      ceftriaxone caused decrease 1,9-fold water absorption. The antibiotics treatment
      within five days didn't change the composition of the fecal and colonic parietal
      microbiota. Azithromycin-induced increase in water absorption was associated with
      upregulation of AQP 8 water channel expression (P < 0.05) in colonic mucosa.
      Ceftriaxone treatment didn't change protein level of AQP8 but induced pro
      inflammatory changes in colonic mucosa structure and mast cells degranulation. We
      showed for the first time the opposite effects ofmacrolide and cephalosporin
      antibiotics on net water transport across rat colonic epithelium.

PMID- 27025049
TI  - [COMPOSITION OF GASTRIC JUICE AND BILE IN RATS AT THE EXPERIMENTAL CHRONIC
      PANCREATITIS].
AB  - Chronic pancreatitis is an inflammatory disease of the pancreas, which is
      characterized by destruction of pancreatic secretory parenchyma and progressing
      exocrine and endocrine insufficiency. Usually these patients have complications
      as cardiovascular, renal, respiratory and liver failure, and various gastric
      dysfunctions. The data of clinical observations do not reveal fully the
      functional state of the stomach and liver in chronic pancreatitis also remains an
      open question about the quality of the gastric juices and bile by this pathology.
      Therefore our aim was to investigate the secretory functions of the stomach and
      liver features in rats at the experimental chronic pancreatitis. This pathology
      modeled using L-arginine. Basal gastric secretion was investigated in chronic
      experiment by aspiration method for 10th and 63rd days, and pancreas and liver-
      in acute experiments at 13th and 68th days after the last administration of L
      arginine. It was established that the character of the secretory response of the
      digestive tract depends on the duration of the pathology course. On the 10th day
      the functional state of the gastric secretory glands in rats with chronic
      pancreatitis characterized by twice increase of gastric acid production but
      decrease the level of hexosamines on 23.8% (P < 0.001) that indicate a increase
      of gastric content aggressiveness and mucus producing cells secretory
      insufficiency. In these animals the rate of total protein decreased on 61.7% (P <
      0.05). On the 13th day observed the increase of pancreatic juice on 332% (P <
      0.01), hepatic secret volume on 74.9% (P < 0.001) and redistribution in the
      cholates spectrum: glycocholates level increased but tauro-, free and total
      dehydroxylated bile acids decreased. These changes suggest deterioration of bile
      detergent properties, inhibition of acidic pathway of bile acids biosynthesis and
      conjugation of cholates with taurine. In two months total deficit of amino acids
      in gastric juice correlated with exocrine pancreatic insufficiency. Herein the
      acidity of gastric content partially restored, while the level of protein and
      mucus secretion proceed to decline. Consequently gastric mucosa is more
      vulnerable. In these rats the rates of free bile acids greatly increased while
      tauro- and glycocholates significantly decreased. Thus the processes of
      hydroxylation and conjugation of bile acids with amino acids inhibited suggesting
      interruption of synthetic and detoxification functions of the liver. The present
      work is important for comprehension the pathophysiological aspects of chronic
      pancreatitis particularly the digestive system functioning features at this
      pathology. These data could be considered in the appointment of treatment to
      avoid complications.

PMID- 27025050
TI  - [CARBOHYDRATE METABOLISM IN TYPE 1 DIABETIC RATS UNDER THE CONDITIONS OF THE
      KIDNEY BEAN PODS AQUEOUS EXTRACT APPLICATION].
AB  - The influence of the aqueous pods extract of kidney bean (Phaseolus vulgaris) on
      indicators of carbohydrate metabolism under the condition of experimental type 1
      diabetes in rats was studied. It was shown that long-term oral administration of
      the extract at a dose of 200 mg/kg to rats leads to the decreasing of blood
      glucose and glycosylated hemoglobin in the background of chronic hypoinsulinemia
      conditions. The use of studied extract led to an increase of glycogen synthase
      activity in rat muscle cells and hexokinase activity in rat liver cells under the
      conditions of type 1 diabetes. It was estimated that administration of the
      aqueous extract to control rats and animals with studied model of diabetes
      increases GLUT-4 protein content in muscle tissue. Thus, the mechanisms of P.
      vulgaris hypoglycemic action can be related with the ability of the particular
      phytoconstituents directly effect on key intracellular elements of insulin target
      tissues carbohydrate metabolism under the conditions of type 1 diabetes.

PMID- 27025051
TI  - [MITOCHONDRIA RESPIRATION AND OXIDATIVE PHOSPHORILATION OF RAT TISSUES AT TAURINE
      PER ORAL INJECTION].
AB  - Taurine--sulphur-containing amino acid is a necessary component of mitochondrial
      matrix, where it maintains pH and is included in mitochondrial transport RNA. But
      still it is unclear how taurine influences on ATP synthesis and mitochondrial
      respiration chain components activity. Thus, the aim of the work was to study the
      effect of long-term per oral taurine injection on mitochondrial respiration
      intensity in rat tissues: liver, brain, testes and thigh muscle. For this purpose
      male Wistar rats, that weighted 190-220 g, were divided in three groups, daily
      during 28 days they were injected drinking water (control group) or taurine
      solution 40 and 100 mg per kg of body weight (I and II research groups,
      correspondingly). Respiration intensity was measured polarogrifically with use of
      Clark electrode at endogenic substrates oxidation (V1), with exogenic alpha
      ketoglutarate (5 mmol/l) or succinate (1 mmol/l;V4S) addition, at ADP addition to
      concentration 200 umol/l (V3), and after ADP depletion (V4ATP). Phosphorylation
      time, oxidative phosphorilation efficacy (ADP/O), respiratory controls by Lardy
      (V3/V4S) and Chance (V3/V4ATP) were calculated. It was found that long term
      taurine injection increased V1 in animal brain and liver of both research groups,
      but it decreased in testes and muscles of I research group. In liver of I
      research group animals, when both alpha-ketoglutarate and succinate were
      oxidated, V4S, V3 and V4ATP were 4-7 times larger than in control. At the same
      time, Lardy respiratory control increased at succinate oxidation, this may
      indirectly point on increased coupling between respiration and oxidative
      phosphorylation. In liver of II research group animals V4S, V3 and V4/ATP when
      alpha-ketoglutarate was oxidated were significantly higher than in control. In
      muscles of I research group V4S, V3 and V4ATP when alpha-ketoglutarate and
      succinate was added were lower than in control. In thigh muscle of II research
      group animals at alpha-ketoglutarate oxidation V3 was higher than in control.
      When succinate was added V4S and V4ATP increased in testes mitochondria of both
      research groups and in brain of I research group. But in II research group
      animals mitochondria V4S brain was lower than in control. At the same time,
      coupling between respiration and oxidative phosphorytation in brain was on
      control level, in testes of I research group it was lower. In testes of II
      research group animals at alpha-ketoglutarate addition increased respiratory
      controls. Thus, the effect of long term per oral taurine injection on
      mitochondria respiration intensity is dose-dependent and tissue-specific and,
      obviously, has different significance and is implemented by different mechanisms.

PMID- 27025052
TI  - [THE EFFECT OF DIETARY RESTRICTION DURING DEVELOPMENT OF DROSOPHILA MELANOGASTER
      ON THE ACTIVITY OF ANTIOXIDANT SYSTEM ENZYMES].
AB  - In the previous study we demonstrated that dietary restriction only at the
      development stage of Drosophila melanogaster may impact the life span of adult
      flies. It was important that we didn't use qualitative (restriction of proteins
      or other macro- or microelements) and not a calorie restriction as well, but
      quantitative dietary restriction that was the proportional reduction of all food
      components in the larval medium. In the situations when the larvae were reared in
      the medium types, that contained protein and carbohydrate components in
      concentrations of 90-10% of food components compared to the standard one (100%),
      the males were characterised with the significant increase in the maximum life
      span. The average life span was also increased, but only in those male
      individuals that developed in the medium types, that contained 50% and 60% of
      food components compared to controls. Such an effect we haven't detected in the
      female flies. To study the biochemical changes associated with the physiological
      effects we have determined the activity of the antioxidant enzymes--superoxide
      dismutase (SOD) and catalase. In the male flies the 50% dietary restriction
      implemented during the development has led to the significant increase in a SOD
      and catalase activity. Also the flies of both sexes reared in the medium with the
      50% of food components have been characterised with the reduction in the
      accumulation of glycation end products. According to these results, we suggest
      that the changes in the activity of antioxidant enzymes may play a role in the
      increase of the flies life span caused by the dietary restriction during the
      development.

PMID- 27025053
TI  - [EFFECT OF HYPOXIA ON SYNAPTIC TRANSMISSION BETWEEN RETINAL GANGLION CELLS AND
      SUPERIOR COLLICULUS NEURONS IN COCULTURE].
AB  - In this study we conducted a series of experiments to characterize the effect and
      define the mechanisms of hypoxia on synaptic transmission between retinal
      ganglion cells and superior colliculus (SC) neurons. Application of hypoxic
      solution leads to a long lasting potentiation (LTP) NMDA-mediated synaptic
      transmission. Analysis of the oxygen deficiency effect on the spontaneous and
      miniature postsynaptic currents (sPSC and mPSC respectively) revealed an increase
      in the frequency of their occurrence and the appearance of the second peak in the
      mPSC histogram distribution. The assessment of quantum and binomial parameters
      reflects the complex pre- and postsynaptic changes during the potentiation,
      independent of the release probability. Most likely this LTP can be caused by an
      increase in the total number of active synapses. Glutamatergic synaptic
      transmission mediated by non-NMDA activation receptor-channel complexes,
      responded to application of deoxygenated solution by the brief depression, which
      is the result of presynaptic dysfunction and associates with decrease in release
      probability and number of active zones. GABAergic synaptic transmission mediated
      by activation GABA(A)-receptor-channel complexes, responded to hypoxic action by
      long term depression (LTD). Analysis of sPSC and mPSC showed a significant
      decrease in the frequency of their occurrence and significant (P = 0.05) decrease
      in the quantum over a period of oxygen deficiency. In general, the effect of
      hypoxia-induced LTD of GABAergic synaptic transmission is based on complex
      changes of presynaptic (independent on the release probability) and postsynaptic
      (reduction sensitivity of receptors in postsynaptic membrane) mechanisms.

PMID- 27025054
TI  - [PHYSIOLOGY AND PHARMACOLOGICAL PROPERTIES OF NANOMATERIALS].
AB  - Literature data and results of our department studies on theoretical and
      practical basics of nanoscience were summarized in the article. Much attention is
      paid to research in the field of physical, chemical, biological, medical,
      physiological, pharmacological, and toxicological properties of nanomaterials
      with the aim of their wider implementation into practice lately. The discovery of
      new quantum/wave properties of nanoparticles is of particular importance. The
      author of the article advances an idea: wave properties of nanomaterials play
      greater role with a decrease in particle size. The preponderance of wave
      properties compared with corpuscular ones in nanostructures determines a great
      change in their physical. chemical properties and an increase in physical,
      mechanical biological, physiological, pharmacological, and toxicologica activity.
      The idea advanced in the article hasn't been verified by theoretical or
      experimental studies for now. Joined efforts of scientists of different
      scientific fields are needed. A confirmation of hypothesis by specific findings
      will be of great importance for physiology, medicine, pharmacology and promote an
      implementation of new efficacious preparations into clinical practice. New
      fundamental discoveries could be made only by multidisciplinary approach.

PMID- 27025055
TI  - FREE RADICALS, REACTIVE OXYGEN SPECIES, OXIDATIVE STRESSES AND THEIR
      CLASSIFICATIONS.
AB  - The phrases "free radicals" and "reactive oxygen species" (ROS) are frequently
      used interchangeably although this is not always correct. This article gives a
      brief description of two mentioned oxygen forms. During the first two-three
      decades after ROS discovery in biological systems (1950-1970 years) they were
      considered only as damaging agents, but later their involvement in organism
      protection and regulation of the expression of certain genes was found. The
      physiological state of increased steady-state ROS level along with certain
      physiological effects has been called oxidative stress. This paper describes ROS
      homeostasis and provides several classifications of oxidative stresses. The
      latter are based on time-course and intensity principles. Therefore
      distinguishing between acute and chronic stresses on the basis of the dynamics,
      and the basal oxidative stress, low intensity oxidative stress, strong oxidative
      stress, and finally a very strong oxidative stress based on the intensity of the
      action of the inductor of the stress are described. Potential areas of research
      include the development of this field with complex classification of oxidative
      stresses, an accurate identification of cellular targets of ROS action,
      determination of intracellular spatial and temporal distribution of ROS and their
      effects, deciphering the molecular mechanisms responsible for cell response to
      ROS attacks, and their participation in the normal cellular functions, i.e.
      cellular homeostasis and its regulation.

PMID- 27025056
TI  - [On the 90th anniversary of Palladin Institute of Biochemistry of NAS of Ukraine:
      about the history and achievements in brief].

PMID- 27025057
TI  - [REPROGRAMMING OF MITOCHONDRIAL ENERGY METABOLISM IN MALIGNANT NEOPLASMS].
AB  - The novel ideas of fundamental role of mitochondria in the maintenance of
      viability of malignant cells have been reviewed. The modern state of research is
      considered in detail, including: mitochondrial control of the cellular redox
      state, sites of reactive oxygen species (ROS) production in inner mitochondrial
      membrane and antioxidant protection systems. Specificities of the structural
      functional mitochondrial remodelling in malignant tumors, the mechanisms of the
      energy metabolism reprogramming, enhancement of the ROS production and adaptation
      to the hypoxic conditions and metabolic stress are analyzed. The available data
      including our research on transplanted tumors indicate that cytotoxic action of
      sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends
      on biological properties of tumors and intensity of structural-functional
      mitochondrial rearrangement. Dichloroacetate turned out to be effective for
      sarcoma 37, but not for Lewis lung carcinoma.

PMID- 27025058
TI  - INHIBITION OF IRE1 MODIFIES EFFECT OF GLUCOSE DEPRIVATION ON THE EXPRESSION OF
      TNFalpha-RELATED GENES IN U87 GLIOMA CELLS.
AB  - Inhibition of IRE1 (inositol requiring enzyme-1), the major signaling pathway of
      endoplasmic reticulm stress, significantly decreases glioma cell proliferation
      and tumor growth. We have studied the expression of TNFalpha-related genes and
      effect of glucose deprivation on these gene expressions in U87 glioma cells over
      expressing dominant-negative IRE1 defective in both kinase and endonuclease (dn
      IRE1) activity of IRE1 with hopes of elucidating its contribution to IRE1
      mediated glioma growth. We have demonstrated that glucose deprivation condition
      leads to down-regulation of the expression of TNFRSF11B, TNFRSF1A,
      TNFRSF10D/TRAILR4, and LITAF genes and up-regulation of TNFRSF10B/TRAILR2/DR5
      gene at the mRNA level in control glioma cells. At the same time, the expression
      of TNFRSF21/DR6, TNFAIP1, TNFAIP3, TRADD, and CD70/TNFSF7 genes in control glioma
      cells is resistant to glucose deprivation condition. The inhibition of IRE1
      modifies the effect of glucose deprivation on LITAF, TNFRSF21, TNFRSF11B, and
      TRADD gene expressions and induces sensitivity to glucose deprivation condition
      the expression of TNFRSF10B, TNFRSF1A, and CD70 genes. We have also demonstrated
      that the expression of all studied genes is affected in glioma cells by
      inhibition of IRE1, except TNFRSF1A gene, as compared to control glioma cells.
      Moreover, the changes in the expression of TNFRSF1A, TNFRSF10D/TRAILR4, and LITAF
      genes induced by glucose deprivation condition have opposite orientation to that
      induced by inhibition of IRE1. The present study demonstrates that fine-tuning of
      the expression of TNFalpha-induced proteins and TNF receptor superfamily genes,
      which related to cell death and proliferation, is regulated by IRE1, an effector
      of endoplasmic reticulum stress, as well as depends on glucose deprivation in
      gene specific manner. Thus, the inhibition of kinase and endoribonuclease
      activity of IRE1 correlates with deregulation of TNFalpha-induced protein genes
      and TNF receptor superfamily genes in gene specific manner and thus slower the
      tumor growth.

PMID- 27025059
TI  - EFFECT OF HYPOXIA ON THE EXPRESSION OF GENES THAT ENCODE SOME IGFBP AND CCN
      PROTEINS IN U87 GLIOMA CELLS DEPENDS ON IRE1 SIGNALING.
AB  - We have studied hypoxic regulation of the expression of different insulin-like
      growth factor binding protein genes in U87 glioma cells in relation to inhibition
      of IRE1 (inositol requiring enzyme-1), a central mediator of endoplasmic
      reticulum stress, which controls cell proliferation and tumor growth. We have
      demonstrated that hypoxia leads to up-regulation of the expression of IGFBP6,
      IGFBP7, IGFBP10/CYR61, WISP1, and WISP2 genes and down-regulation--of IGFBP9/NOV
      gene at the mRNA level in control glioma cells, being more signifcant changes for
      IGFBP10/CYR61 and WISP2 genes. At the same time, inhibition of IRE1 modifies the
      effect of hypoxia on the expression of all studied genes: eliminates sensitivity
      to hypoxia the expression of IGFBP7 and IGFBP9/NOV genes, suppresses effect of
      hypoxia on IGFBP6, IGFBP10/CYR61, and WISP2 genes, and slightly enhances hypoxic
      regulation of WISP1 gene expression in glioma cells. We have also demonstrated
      that the expression of all studied genes in glioma cells is regulated by IRE1
      signaling enzyme upon normoxic condition, because inhibition of IRE1
      significantly up-regulates IGFBP7, IGFBP10/CYR61, WISP1, and WISP2 genes and down
      regulates IGFBP6 and IGFBP9/NOV genes as compared to control glioma cells. The
      present study demonstrates that hypoxia, which contributes to tumor growth,
      affects all studied IGFBP and WISP gene expressions and that inhibition of IRE1
      preferentially abolishes or suppresses the hypoxic regulation of these gene
      expressions and thus possibly contributes to slower glioma growth. Moreover,
      inhibition of IRE1, which correlates with suppression of cell proliferation and
      glioma growth, is down-regulated expression of pro-proliferative IGFBP genes,
      attesting to the fact that endoplasmic reticulum stress is a necessary component
      of malignant tumor growth.

PMID- 27025060
TI  - THE EFFECT OF NITRIC OXIDE ON SYNAPTIC VESICLE PROTON GRADIENT AND MITOCHONDRIAL
      POTENTIAL OF BRAIN NERVE TERMINALS.
AB  - The effect of nitric oxide on synaptic vesicle proton gradient and membrane
      potential of rat brain nerve terminals was studied. It has been shown that nitric
      oxide in the form of S-nitrosothiols at nanomolar concentrations had no effect on
      the studied parameters, but caused a rapid dissipation of synaptic vesicle proton
      gradient and depolarization of mitochondrial membrane in the presence of a SH
      reducing compound such as dithiothreitol. Both processes were reversible and the
      rate of H(+)-gradient restoration depended on the redox potential of nerve
      terminals, namely the molar ratio of reductant/oxidant. This facts, as well as
      insensitivity of the studied processes to the inhibitor of NO-sensitive guanylate
      cyclase such as ODQ, allow suggesting that post-translational modification of
      thiol residues of the mitochondrial and synaptic vesicle proteins underlies the
      effect of nitric oxide on the key functional parameters ofpresynaptic nerve
      terminals.

PMID- 27025061
TI  - THE EFFECT OF THE ALUMINUM CHLORIDE--QUERCETIN COMPLEX ON Ca2+, Mg(2+)-ATPase
      ACTIVITY AND CONTRACTION DYNAMIC PROPERTIES OF MUSCLE TIBIALIS ANTERIOR FROM RANA
      TEMPORARIA.
AB  - Combined effect of aluminum chloride and quercetin solutions on the enzymatic
      activity and contraction dynamics of muscle fiber bundles of the Rana temporaria
      m. tibialis anterior was investigated. It was shown that these complexes inhibit
      muscle contraction. Linear reduction of Ca2+, Mg(2+)-ATPase activity induced by
      all of the used concentrations of AlCl3 - quercetin was demonstrated. It was
      found that complex of quercetin with AlCl3 has a greater inhibitory effect on
      muscle contraction dynamic and causes greater reduction during all periods of
      stimulation in comparison to the separate effect of the investigated compounds.
      All the studied concentrations of AlCl3 and quercetin solutions (AlCl3: 10(-4)
      10(-2) M; quercetin: 10(-6)-10(-5) M) caused concentration depended contraction
      strengths and lengths reduction. The decrease in strength and length of muscle
      contractions was of constant and mostly linear nature within observed timeframe
      as well as within each periods of contraction. The changes were least pronounced
      within pretetanic period, but were profound within terminal period of muscle
      activity. The changes in dynamic contraction properties and Ca2+, Mg(2+)-ATPase
      activity of sarcoplasmic reticulum under effect of the investigated compounds was
      minimal in the beginning of the muscle's response to stimulus, prior to muscle
      strength reaching stable contraction level.

PMID- 27025062
TI  - PROTECTIVE EFFECTS OF POTASSIUM TRANSPORT IN MITOCHONDRIA FROM RAT MYOMETRIUM
      UNDER ACTIVATION OF MITOCHONDRIAL PERMEABILITY TRANSITION PORE.
AB  - We demonstrated using PBFI K(+)-sensitive fluorescent probe an enhancement of
      both components of K(+)-cycle--the ATP-sensitive K(+)-uptake and quinine
      sensitive K+/H(+)-exchange--under the Ca2+ induced opening of mitochondrial
      permeability transition pore (MPTP) in rat myometrium mitochondria. Addition of
      CaCl2 (100 MUM to K(+)-free medium results in the enhancement of reactive oxygen
      species (ROS) production, which was eliminated by cyclosporine A. Addition of
      CaCl2 to K(+)-rich medium did not increase the rate of ROS production, but
      blocking of mitoK+(ATP)-channels with glybenclamide (10 mcM increased production
      of ROS. We conclude that K(+)-cycle exerts a protective influence in mitochondria
      from rat myometrium by regulation of matrix volume and rate of ROS production
      under the condition of Ca(2+)-induced MPTP.

PMID- 27025063
TI  - CALIX[4]ARENE C-99 INHIBITS MYOSIN ATPase ACTIVITY AND CHANGES THE ORGANIZATION
      OF CONTRACTILE FILAMENTS OF MYOMETRIUM.
AB  - Calix[4]arenes are cup-like macrocyclic (polyphenolic) compounds, they are
      regarded as promising molecular "platforms" for the design of new physiologically
      active compounds. We have earlier found that calix[4]arene C-99 inhibits the
      ATPase activity of actomyosin and myosin subfragment-1 of pig uterus in vitro.
      The aim of this study was to investigate the interaction of calix[4]arene C-99
      with myosin from rat uterine myocytes. It was found that the ATPase activity of
      myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was
      almost 50% lower than in control. Additionally, we have revealed the effect of
      calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus
      myocytes by the method of confocal microscopy. This effect can be caused by
      reorganization of the structure of the contractile smooth muscle cell proteins
      due to their interaction with calix[4]arene. The obtained results demonstrate the
      ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and
      affect not only the myosin ATPase activity, but also the structure of the actin
      and myosin filaments in the myometrial cells. Demonstrated ability of
      calix[4]arene C-99 can be used for development of new pharmacological agents for
      efficient normalization of myometrial contractile hyperfunction.

PMID- 27025064
TI  - SIGNAL MEDIATORS AT INDUCTION OF HEAT RESISTANCE OF WHEAT PLANTLETS BY SHORT-TERM
      HEATING.
AB  - The effects of functional interplay of calcium ions, reactive oxygen species
      (ROS) and nitric oxide (NO) in the cells of wheat plantlets roots (Triticum
      aestivum L.) at the induction of their heat resistance by a short-term influence
      of hyperthermia (heating at the temperature of 42 degrees C during 1 minute) have
      been investigated. The transitional increase of NO and H2O2 content, invoked by
      heating, was suppressed by the treatment of plantlets with the antagonists of
      calcium EGTA (chelator of exocellular calcium), lanthanum chloride (blocker of
      calcium channels of various types) and neomycin (inhibitor of
      phosphatidylinositol-dependent phospholipase C). The rise of hydrogen peroxide
      content, caused by hardening, was partially suppressed by the action of
      inhibitors of nitrate reductase (sodium wolframate) and NO-synthase (N(G)-nitro-L
      arginine methyl ester--L-NAME), and the increasing of nitric oxide content was
      suppressed by the treatment of plants with the antioxidant ionol and with the
      scavenger of hydrogen peroxide (dimethylthiourea). These compounds and
      antagonists of calcium also partially removed the effect of the rise of
      plantlets' heat resistance, invoked by hardening heating. The conclusion on
      calcium's role in the activation of enzymatic systems, generating reactive oxygen
      species and nitric oxide, and on the functional interplay of these signal
      mediators at the induction of heat resistance of plantlets by hardening heating
      is made.

PMID- 27025065
TI  - EXPERIMENTAL SUBSTANTIATION OF PERMEABILIZED HEPATOCYTES MODEL FOR INVESTIGATION
      OF MITOCHONDRIA IN SITU RESPIRATION.
AB  - To verify experimentally the model of permeabilized hepatocytes, the degree of
      cell permeability was assessed using trypan blue and polarographycally determined
      cell respiration rate upon succinate (0.35 mM) and a-ketoglutarate (1 mM)
      oxidation. Oxidative phosphorylation was stimulated by ADP (750 MUM). Hepatocyte
      permeabilization depends on digitonin concentraion in medium and on the number of
      cells in suspension. Thus, the permeabilization of 0.9-1.7 million cells/ml was
      completed by 25 MUg/ml of digitonin, permeabilization of 2.0-3.0 million cells/ml
      -by 50 MUg/ml of digitonin and permeabilization of 4.0-5.6 million cells/ml--by
      100 MUg/ml. Thus, the higher is the suspension density, the higher digitonin
      concentration is required. Treatment of hepatocytes with digitonin resulted in a
      decrease of endogenous respiration rate to a minimum upon 20-22 MUg of digitonin
      per 1 million cells. Supplementation of permeabilized hepatocytes with alpha
      ketoglutarate maintained stable respiration rate, on the level higher than
      endogenous respiration at the corresponding digitonin concentration, unlike the
      intact cells. Respiration rate of permeabilized hepatocytes at the simultaneous
      addition of alpha-ketoglutarate and ADP increased to the level of intact cell
      respiration, irrespective of digitonin concentration. Addition of solely
      succinate and especially succinate plus ADP markedly intensified the respiration
      of permeabilized hepatocytes to the level higher than that of intact cells. The
      dependence of succinate-stimulated respiration on digitonin concentration reached
      maximum at 20-22 alphag of digitonin per 1 million cells. Optimal ratio of
      digitonin amount and the cell number in suspension is expected to be different in
      various tissues.

PMID- 27025066
TI  - RHAMNAZIN INHIBITS PROLIFERATION AND INDUCES APOPTOSIS OF HUMAN JURKAT LEUKEMIA
      CELLS IN VITRO.
AB  - Antiproliferative and apoptogenic effects of rhamnazin, a dimethoxylated
      derivative of quercetin, were studied in human acute lymphoblastic leukemia
      Jurkat cells. The cytotoxicity and apoptogenic activity of rhamnazin in vitro are
      inferior to that of quercetin. The apoptogenic activity of rhamnazin is realized
      via mitochondrial pathway and associated with activation of caspase-9 and -3. The
      additive apoptogenic effect of rhamnazin and suboptimal doses of etoposide, a DNA
      topoisomerase II inhibitor, is demonstrated. Therefore, methylation of quercetin
      modifies its biological effects considerably.

PMID- 27025067
TI  - RESPONSE OF PHENOLIC METABOLISM INDUCED BY ALUMINIUM TOXICITY IN FAGOPYRUM
      ESCULENTUM MOENCH. PLANTS.
AB  - Buckwheat genus (Fagopyrum Mill.) is one of the aluminium tolerant taxonomic
      units of plants. The aim of the study was an evaluation of the aluminium (50 MUM
      effect on phenolic accumulation in various parts of buckwheat plants (Fagopyrum
      esculentum Moench). Detection of increasing of total phenolic content, changes in
      flavonoid and anthocyanin content and phenylalanine ammonia-lyase activity (PAL)
      were revealed over a period of 10 days of exposure to aluminium. The most
      significant effects of aluminium treatment on phenolic compounds accumulation
      were total phenolic content increasing (by 27.2%) and PAL activity rising by 2.5
      times observed in leaves tissues. Received data could be helpful to understand
      the aluminium tolerance principles and relationships of phenolic compounds to
      aluminium phytotoxicity.

PMID- 27025068
TI  - INFLUENCE OF BACILLUS AMYLOLIQUEFACIENS SUBSP. PLANTARUM IMV B-7404 STRAIN
      EXOMETABOLITES ON PHENYLALANINE AMMONIA-LYASE ACTIVITY IN WINTER WHEAT SEEDLINGS.
AB  - Influence of Bacillus amyloliquefaciens subsp. plantarum IMV B-7404 strain
      exometabolites on phenylalanine ammonia-lyase (PAL, EC 4.3.1.24) activity in
      winter wheat seedlings has been studied. A significant increase of PAL activity
      at 4-6 hours after treatment of plant roots with Bacillus amyloliquefaciens
      subsp. plantarum IMVB-7404 strain exometabolites and in case of leaves infection
      with Bipolaris sorokiniana plant pathogen has been shown. It was established that
      PAL activity changed along with a decrease of the infected surface area of the
      leaves evidenced for the induction of response in winter wheat seedlings induced
      by IMV B-7404 strain exometabolites. It was concluded that the studied exponents
      could be used as model systems in the research of phytoimmunity induction
      mechanisms.

PMID- 27025069
TI  - [COMPUTATIONAL MODELING OF MOLECULAR DYNAMICS OF G41R MUTANT FORM OF HUMAN
      TYROSYL-tRNA SYNTHETASE, ASSOSIATED WITH CHARCOT-MARIE-TOOTH NEUROPATHY].
AB  - The computational structural models of human tyrosyl-tRNA synthetase and its
      mutant form G41R (Charcot-Marie-Tooth associated) were constructed, while their
      whole structural coordinates are still unknown. Grid-services of MolDynGrid
      Virtual Laboratory and Ukrainian National Grid-infrastructure were used for
      molecular dynamics (MD) simulations. The analyses of trajectories of MD
      simulations have shown the beta-sheet formation in region Lys147 - Glu157 between
      H9 and H10 helices (CP1 insertion of Rossman fold) for G41R mutant.

PMID- 27025070
TI  - COMPUTER PREDICTION OF BIOLOGICAL ACTIVITY OF DIMETHYL-N-(BENZOYL)AMIDOPHOSPHATE
      AND DIMETHYL-N-(PHENYLSULFONYL)AMIDOPHOSPHATE, EVALUATION OF THEIR CYTOTOXIC
      ACTIVITY AGAINST LEUKEMIC CELLS IN VITRO.
AB  - Structural analogues of beta-diketones--dimethyl-N-(benzoyl)amidophosphate (HCP)
      and dimethyl-N-(phenylsulfonyl)amidophosphate (HSP) were synthesized and
      identified by the methods of IR, 1H and 31P NMR spectroscopy. Screening of
      biological activity and calculation of physicochemical parameters of HCP and HSP
      compounds were done with the use of PASS and ACD/Labs computer programs. A wide
      range of biological activity of synthesized compounds, antitumor activity in
      particular, has been found. Calculations of the bioavailability criteria indicate
      that the investigated compounds have no deviations from Lipinski's rules. HCP
      compound is characterized by a high lipophilicity at physiological pH as compared
      to HSP. It was found that cytotoxic effect of the studied compounds on the
      leukemic L1210 cells was of time- and dose-dependent character. HCP is
      characterized by more pronounced and early cytotoxic effects as compared to HSP.
      It was shown that 2.5 mM HCP increased ROS production 3 times in the early period
      of incubation, and decreased cell viability by 40% after 48 h, and by 66%--after
      72 h. Based on the computer calculation and undertaken research, HCP was selected
      for target chemical modifications and enhancement of its antitumor effect.

PMID- 27025071
TI  - [The history of creation and study of vitamin D medicines in the Laboratory of
      Medical Biochemistry of Palladin Institute of Biochemistry of NAS of Ukraine for
      1990-2015].

PMID- 27025073
TI  - [Introduction].

PMID- 27025072
TI  - [The hypothetical pathogenesis of Alzheimer's disease based on age-related
      changes in brain].

PMID- 27025074
TI  - [New diagnostic guidelines for Alzheimer's disease by NIA/AA].
AB  - In 2011, the National Institute on Aging and the Alzheimer's Association (NIA/AA)
      published new guidelines for the diagnosis of Alzheimer's disease (AD) twenty
      seven years after old guidelines had been published. The working groups
      recognized the whole clinical trajectory of AD as consisting of three defined
      stages, namely, AD dementia, mild cognitive impairment due to AD and preclinical
      AD. In addition to some refinements of descriptions of clinical features, based
      on recent scientific evidences of biomarkers, biomarker evidence was incorporated
      into the diagnostic criteria for AD dementia and mild cognitive impairment(MCI)
      due to AD to enhance diagnostic accuracy in research settings. Preclinical AD is
      newly defined as the earliest phase with presence of biomarker evidence
      suggesting AD pathophysiology and completely absence of clinical manifestation or
      absence of clinical symptom above subtle cognitive decline which falls short of
      meeting criteria for MCI. The diagnostic criteria enable disease modifying drug
      trials for subjects with earlier stage of AD pathology. Note that these criteria
      incorporating biomarker evidence are solely intended for research purposes.
      Further biomarker researches targeting subjects with early stage, especially
      preclinical AD are needed for refinement and broader usage of new guidelines.

PMID- 27025075
TI  - [Prevention of dementia].
AB  - The dementia prevention consists of three steps, primary prevention of dementia
      is to prevent from normal and mild cognitive impairment to dementia, secondary
      prevention is early detection and early treatment of dementia, and tertiary
      prevention is three stages of progress prevention of dementia. Primary prevention
      of dementia had been considered impossible until recently, but potential
      scientific evidence has been shown recently. The fact that 4.62 million people
      are person with dementia and 400 million people are person with mild cognitive
      impairment are considered to be urgent problem and we must intend to perform
      dementia prevention from primary to tertiary prevention thoroughly. We perform
      dementia screening using touch panel type computer and we recommend person with
      mild cognitive impairment to join dementia prevention classroom. Therefore, we
      can prevent progression from mild cognitive impairment to dementia (primary
      prevention). Early diagnosis and introduction to the specialized medical
      institution are needed if you find early stage of dementia and treat early
      (secondary prevention). To prevent progression by the appropriate drug treatment
      and care for dementia is required (tertiary prevention).

PMID- 27025076
TI  - [Amyloid imaging].
AB  - Amyloid imaging is a non-invasive technique that enable us to visualize the
      distribution of fibrillar amyloid beta deposition in the living human brain. This
      new imaging technique dramatically accelerated the clinical investigation of
      early phase of Alzheimer's disease (AD) in the last decade, and now it becomes an
      essential tool for the observational and interventional prospective studies
      focusing on prodromal and preclinical AD. In current situations in the advent of
      effective disease modifying drugs, application of amyloid imaging in clinical
      practice will be limited to the differential diagnosis of dementia of young onset
      or atypical clinical presentations. Perspectives on future pathological and
      therapeutic research will be mentioned.

PMID- 27025077
TI  - [Tau imaging].
AB  - Several promising tau imaging probes have been developed by Tohoku University
      ([18F]THK series), National Institute of Radiological Sciences([11C]PBB3), Eli
      Lilly ([18F]T807), and Hoffman-La Roche ([18F]R06958948). In this paper we
      discussed some of the criteria required for the tau imaging probe in Alzheimer's
      disease. It will be certain that tau imaging plays an important role in an
      accurate diagnosis and as companion diagnostics.

PMID- 27025078
TI  - [The trend of developing new disease-modifying drugs in Alzheimer's disease].
AB  - Development of symptomatic treatment of Alzheimer s disease by cholinesterase
      inhibitors like donepezil was successful. However, it is a disappointment that
      development of disease-modifying drugs such as anti-amyloid drug based on amyloid
      cascade theory has been interrupted or unsuccessful. Therefore, we have to be
      more cautious regarding inclusion criteria for clinical trials of new drugs. We
      agree that potentially curative drugs should be started before symptoms begin as
      a preemptive therapy or prevention trial. The concept of personalized medicine
      also is important when ApoE4-related amyloid reducing therapy is considered.
      Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry
      of Health, Labour and Welfare gave a final remark that there was nothing wrong in
      the data managing process in the J-ADNI data center. We should pay more attention
      to worldwide challenges of speeding up new drug development.

PMID- 27025079
TI  - [Significance and progress of DIAN/A4/API].
AB  - The DIAN observational study compared the pathophysiological markers between
      mutation carriers and non-carriers for autosomal dominant Alzheimer's disease. It
      has revealed the biomarker changes in the mutation carrier's brain started as
      early as 20, even 25 years prior to symptoms. The researchers of DIAN started the
      prevention trial(DIAN-TU) with two monoclonal antibodies. The API study is the
      clinical trial of the anti-amyloid monoclonal antibody therapy to the kindred of
      early onset familial AD (EOAD) who carry the PSEN1 E280A mutation. This study has
      also shown the same biomarker changes that were reported in the DIAN study. Anti
      Amyloid Treatment in Asymptomatic AD (A4) is a prevention trial aimed at treating
      cognitive normal older individuals at risk of developing Alzheimer's disease
      dementia on the basis of having biomarker evidence of amyloid (pre-clinical AD).
      Solanezumab was selected for the anti-amyloid treatment for A4.

PMID- 27025080
TI  - [Immunotherapy for Alzheimer's disease targeting Abeta].
AB  - Active and passive immunization of Alzheimer model mice with Abeta showed
      clearance of aggregated amyloid beta deposits and improved memory and learning.
      Although human trial was halted because of autoimmune encephalitis, the trial
      revealed that immunization with Abeta also deleted amyloid deposits in humans
      without clinical benefit. On these proof of concept, several clinical trials
      using monoclonal antibodies are on-going. Although solanezumab which recognizes
      Abeta monomer turned out ineffective in the primary endpoint, it showed
      significant beneficial effect in mild AD cases in the secondary outcome.
      Solanezumab is now on a large scale phase III trial in mild AD cases in the
      world. If it turns out to be effective, it will be the first disease modifying
      drug for AD in a few years. However, since monoclonal antibodies are extremely
      expensive, less expensive and long acting active immunization will be widely
      accepted. More effective and sophisticated vaccines such as DNA vaccine and
      recombinant viral vaccines will be utilized in future.

PMID- 27025081
TI  - [BACE1 inhibitors for the treatment of Alzheimer disease].
AB  - beta-Site amyloid precursor protein cleaving enzyme 1 (BACEl) is the enzyme
      required for the production of the amyloid-beta peptide(Abeta), which is
      associated with Alzheimer disease (AD). BACEl has emerged as a prime molecular
      target for reducing the brain Abeta levels. Recently, several BACEl inhibitors
      have been developed in clinical trials to test the efficacy in AD patients and
      individuals with prodromal AD. However, identification of BACE1 substrates and
      phenotypes of Bace1 knockout mice have raised concerns regarding potential
      mechanism-based adverse effects. This review summarizes the current status of the
      development of BACE1 inhibitors and the evaluation of their therapeutic potential
      against AD.

PMID- 27025082
TI  - [The proceeding of drug development based on the propagation of tau protein].
AB  - Many neurodegenerative diseases accompanied by dementia are associated with the
      accumulation of protein aggregates. These aggregates are thought to be causes of
      progressive neurodegeneration and death of neurons. Recent studies indicated that
      these aggregates could propagate between cells in a prion like manner. Once a
      protein aggregate is formed it can transmit cell to cell and affect broad regions
      of brain. Some neurodegenerative diseases such as Alzheimer's disease are
      associated with the pathological aggregation of tau protein. Thus, these diseases
      are named as tauopathies. In the brain of these diseases, aggregated tau must
      also propagate in a prion like manner. Here, we discuss about the therapeutic
      approaches against dementia based on the prion like propagation of tau proteins.

PMID- 27025083
TI  - [Defining and disease-modifying therapy for the preclinical stages of Alzheimer's
      disease].
AB  - The pathophysiological process of Alzheimer's disease (AD) is thought to begin
      more than twenty years before the diagnosis of AD dementia. Recent studies
      provided the biomarker of AD pathological changes. Biomarkers of brain Abeta
      amyloidosis include reduction in cerebrospinal fluid (CSF) Abeta42 and increased
      amyloid tracer retention on positron emission tomography(PET) imaging. Elevated
      CSF tau is thought to be a biomarker of neuronal injury. The Natinal Institute on
      Aging and the Alzheimer's Association proposed AD dementia, mild cognitive
      impairment due to AD, the preclinical stage of AD. These recommendation for the
      biomarker of AD are intended for research purposes at this time. Some disease
      modifying therapies may be effective for the preclinical stage of AD.

PMID- 27025084
TI  - [Dementia study using induced pluripotent stem cells].
AB  - Recent developments in induced pluripotent stem cell (iPSC) technology have
      facilitated, and have contributed to overcome the difficulty of modeling dementia
      caused by Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and
      frontotemporal lobar degeneration (FTLD), etc. The following models using iPSCs
      were reported: the pathophysiology caused by gene mutations such as presenilin or
      amyloid beta precursor protein in AD, alpha-synuclein in DLB, and microtubule
      associated protein tau, fused in sarcoma, progranulin, or chromosome 9 open
      reading frame 72 in FTLD, anti-AD drug screening, sortilin-related receptor L 1
      haplotype influence in sporadic AD, and amyloid beta secretion in Down syndrome.
      Patient-specific iPSC could be expected to reveal the disease pathology and lead
      to drug discoveries for dementia patients.

PMID- 27025085
TI  - [Subjective memory complaints (SMC)].
AB  - Subjective memory complaints without objective cognitive impairments are common
      in elderly people. Recent evidence indicates subjective memory complaints is not
      merely a sign of a depressive state or an aging phenomenon, but an important risk
      factor for proceeding to mild cognitive impairment (MCI) and dementia in the
      future. Even when cognitively intact through the life, people with SMC tend to
      have more Alzheimer's disease (AD) pathology in the brain, which recently been
      defined as preclinical AD. Though not having the same clinical significance
      compared to MCI, we should keep in mind that elderly people with SMC are at risk
      for future cognitive decline and try to find out what specific biological
      backgrounds or clinical characters increase this cognitive risk.

PMID- 27025086
TI  - [Mild cognitive impairment].
AB  - Mild cognitive impairment(MCI) is considered to be a transition state between
      normal cognition and dementia. The subtypes of MCI are highly heterogeneous in
      terms of etiology, presentation, and prognosis. Patients with the amnestic
      subtype of MCI are at a high risk of progression to Alzheimer disease (AD); this
      subtype may represent the prodromal stage of AD. Moreover, patients with MCI who
      are not aware of their memory deficits and in whom practice effects are not
      observed exhibit parietotemporal hypoperfusion on single photon emission CT,
      indicating that these findings are predictors of progression to AD. In this
      review, I have discussed the most current aspects related to the concept and
      clinical presentation of MCI.

PMID- 27025087
TI  - [New entities and the criteria of FTLD].
AB  - This article provides an overview of the historical entity hitherto, the pivotal
      clinical symptoms of FTLD (frontotemporal lobar degeneration), and an
      introduction for the revised criteria for bvFTD (behavioral variant
      frontotemporal dementia): FTDC (International Behavioral Variant FTD Criteria
      Consortium) presented by Rascovsky et al(2011), and the classification criteria
      for PPA(primary progressive aphasia) heralded by Gorno-Tempini et al (2011).
      According to the former criteria, bvFTD can be diagnosed by the clinical symptoms
      as having possible bvFTD or probable bvFTD, and the pathological findings could
      lead definite bvFTD. In the latter classification criteria of PPA, two types are
      implicated in FTLD: one is the non-fluent/agrammatic variant
      PPA(PNFA/nfvPPA/naPPA), and the other is semantic variant PPA(SD/svPPA).

PMID- 27025088
TI  - [Transient epileptic amnesia].
AB  - Transient amnesia is one of common clinical phenomenon of epilepsy that are
      encountered by physicians. The amnestic attacks are often associated with
      persistent memory disturbances. Epilepsy is common among the elderly, with
      amnesia as a common symptom and convulsions relatively uncommon. Therefore,
      amnesia due to epilepsy can easily be misdiagnosed as dementia. The term
      'transient epileptic amnesia (TEA)' was introduced in the early 1990s by Kapur,
      who highlighted that amnestic attacks caused by epilepsy can be similar to those
      occurring in 'transient global amnesia', but are distinguished by features
      brevity and recurrence. In 1998, Zeman et al. proposed diagnostic criteria for
      TEA.

PMID- 27025089
TI  - [Primary age-related tauopathy (PART): a novel term to describe age-related
      tangle pathology encompassing a wide range from cognitively normal condition to
      senile dementia of the neurofibrillary tangle type].
AB  - It has been reported that neurofibrillary tangles (NFTs) are commonly observed in
      older people, and that some of older individuals with dementia have a large
      amount of NFTs in the medial temporal lobe without amyloid(Abeta) plaques, which
      have been referred to as senile dementia of the NFT type (SD-NFT), tangle
      predominant senile dementia (TPSD), or tangle-only dementia. In 2014, our
      international collaborative group proposed a new term, "primary age-related
      tauopathy(PART)", to describe such age-related tangle pathology, clinically
      encompassing a wide range from normal to cognitive impairment/ dementia (SD-NFT).
      This nomenclature would provide a conceptual foundation for future studies
      leading to development of clinical diagnosis for this condition.

PMID- 27025090
TI  - [Pick's disease].
AB  - Pick's disease is a type of frontotemporal lobar degeneration(FTLD) with
      circumscribed atrophy in the frontotemporal lobe. The terminology for Pick's
      disease has evolved over time. Pick's disease was a term formerly used to define
      a disorder with symptoms caused by frontal and temporal lobe dysfunction.
      Therefore, the diagnosis was previously based on clinical features and the
      distribution of brain atrophy. Pick's disease is currently defined by the
      presence of tau-positive Pick bodies, and thus can be diagnosed only
      pathologically. The clinical phenotypes of Pick's disease include behavioral
      variant FTD (bvFTD), progressive nonfluent aphasia (PNFA) and semantic dementia
      (SD).

PMID- 27025091
TI  - [Dementia with Lewy bodies].
AB  - It is important to differentiate dementia with Lewy bodies (DLB) and other
      dementia, especially Alzheimer disease (AD), because the medical treatment,
      management, and the prognosis of these diseases are different. In regard to
      clinical features, DLB patients have relatively mild memory disturbance,
      fluctuating cognition, more severe disturbances of attention, executive function,
      visuospacial function, visual hallucination, depression, autonomic symptoms, REM
      sleep behavior disorder, and idiopathic parkinsonism compared to AD patients. In
      regard to imaging tools, DLB patients have milder atrophy of medial temporal lobe
      by brain MRI, reduced occipital activity by SPECT or PET, reduced MIBG uptake by
      MIBG cardiac scintigraphy, and low dopamine transporter activity in the basal
      ganglia by SPECT or PET.

PMID- 27025092
TI  - [Vascular dementia: an update].
AB  - The concept of vascular dementia(VaD) has been under discussion for long time.
      The most widely used guideline is NINDS-AIREN. However, this guideline tends to
      emphasize memory impairment, which seems very unrealistic in some cases. Although
      several guidelines have been created in addition to NINDS-AIREN, each of these
      guidelines has its advantages and disadvantages. With respect to the
      pathophysiology, there have been recent important findings, particularly about
      subcortical vascular dementia(SVD). From the therapeutic point of view, there
      have been high expectations for cholinesterase inhibitors and memantine, but the
      effectiveness of these drugs has not proved impressive so far. In this
      manuscript, we summarized the concept of VaD. In addition, we described recent
      findings related to pathophysiology and medication by cholinesterase inhibitors
      and memantine.

PMID- 27025093
TI  - [Diabetes-related dementia].
AB  - Type 2 diabetes mellitus (DM) has been shown to increase the risk of cognitive
      decline and dementia, such as Alzheimer's disease (AD) and vascular dementia.
      Among subjects with dementia and DM, there is a dementia subgroup with
      characteristics predominantly associated with DM-related metabolic abnormalities
      rather than AD or vascular pathology. The subgroup was characterized by old age,
      high hemoglobin A1c level, long duration of diabetes, high frequency of insulin
      therapy, low frequency of apolipoprotein E4 carrier status, less severe medial
      temporal lobe atrophy, impaired attention but less impaired word recall, and
      slower progression of cognitive impairment, referred to as "diabetes-related
      dementia". The identification of diabetes-related dementia may be necessary for
      considering an appropriate therapy and prevention in clinical practice.

PMID- 27025094
TI  - [Medical services for dementia in the Comprehensive Strategy to Accelerate
      Dementia Measures (New Orange Plan)].
AB  - The way to provide medical services for dementia was reviewed in the context of
      the Comprehensive Strategy to Accelerate Dementia Measures (New Orange Plan). The
      basic structure of service providing system consists of the primary and secondary
      care services. Both are expected to function in the context of the community
      based integrated care system. Because of regional differences, prefectural
      government should take measures to make the Medical Center for Dementia function
      depending on local circumstances. Psychiatric services and general hospitals are
      expected to provide mental health services and treatment for concurrent medical
      conditions, respectively. Home medical care is expected to be fundamental
      services for persons with advanced-stage dementia. In super-aging society, the
      standard medical service for older persons should be adapted to older persons
      living with dementia.

PMID- 27025095
TI  - [Frailty and sarcopenia: a new bridge to dementia].
AB  - Frailty is a predictor of functional decline, falls, hospitalization, and
      mortality. Fried et al. developed the frailty index, which include 5 simple
      items: weight loss, weakness, exhaustion, slowness, and low activity. Likewise,
      sarcopenia indicates an age-related decline in skeletal muscle mass as well as
      muscle function, which may result in reduced physical capability, poorer quality
      of life, impaired cardiopulmonary performance, unfavorable metabolic effects,
      falls, disability, and mortality. Both frailty and sarcopenia could be associated
      with mild cognitive impairment which leads to dementia. Thus, early initiation of
      a comprehensive geriatric health examination and a multidomain intervention such
      as diet, exercise, cognitive training, and vascular risk monitoring may be useful
      to prevent frailty and sarcopenia in community-dwelling older adults.

PMID- 27025096
TI  - [Drug-induced dementia].
AB  - Many drugs have been reported to induce not only delirium but also cognitive
      impairment. Some types of drugs are reported to induce dementia, and prolonged
      hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral
      antidiabetic drugs could result in dementia. Recently, taking multiple drugs with
      anticholinergic activity are reported to cause cognitive decline and
      anticholinergic burden should be avoided especially in patients with dementia.
      Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to
      the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and
      withdrawal of the offending drug is essential to improve cognitive function.

PMID- 27025097
TI  - [A real-world survey on antipsychotic treatment for BPSD].
AB  - Despite US Food and Drug Administration black box warning, antipsychotics are
      frequently used for behavioral and psychological symptoms of dementia (BPSD) of
      Alzheimer's disease (AD). A 24-weeks prospective cohort study of 10,079 Japanese
      AD patients in. 357 medical sites was done. The mortality rates in the whole
      exposed group did not differ from those in the non-user control group. However,
      further analysis disclosed that the exposed group with shorter treatment periods
      had higher mortality risk. The results confirmed the mortality associated with
      antipsychotics suggesting that new use of antipsychotics should be avoided.
      Patients having been maintained on the drugs for long periods may be at less
      risk.

PMID- 27025098
TI  - [What we did and learnt in the care of the patients with dementia after the Great
      East Japan Earthquake in 2011].
AB  - Northeast Japan experienced an earthquake of magnitude 9.0, followed by enormous
      tsunamis on March 11th 2011. "The Great East Japan Earthquake" greatly affected
      health conditions of elderly people. Our group has reported that cognitive
      functions of elders were negatively influenced by this disaster. Several reasons
      of the cognitive deterioration could be considered such as (1) changes in the
      living circumstance, (2) loss of families, relatives, and friends, (3) loss of
      their daily activities such as farming and fishing, and (4) isolation from
      families and neighbors. We are now performing some anti-dementia programs
      including exercise, diet, and management for lifestyle-related disorders to
      prevent dementia.

PMID- 27025099
TI  - [Molecular mechanisms for collective cell migration--perspectives and approaches
      from the studies on the actin-binding protein Girdin].
AB  - In embryonal development and pathogenesis of diseases, cells often get connected
      and form small groups to undergo "collective migration", rather than spread out
      individually. The examples include the migration of neural crest cells and
      neuroblasts during development and the invasion of cancers in surrounding stroma,
      indicating the importance and significance of collective behavior of cells in the
      body. Recent studies have revealed the mechanisms for collective cell migration,
      which had seemed not to be the subject of traditional cell biology on single
      cells in culture. The heterogeneity in cell groups is also a key in understanding
      the mechanisms for collective cell migration. In this article, we describe
      recently emerging mechanisms for collective cell migration, with a particular
      focus on our studies on the actin-binding protein Girdin and tripartite motif
      containing 27.

PMID- 27025100
TI  - [SEX HORMONE INFLUENCE ON PERIPHERAL NATURAL KILLER CELLS COUNT].
AB  - Proper evaluation of immunological factors connected with pregnancy establishment
      increased the possibility for exact treatment in high risk gestation cases.
      Hormonal changes during an ovarian cycle may affect immune response, which is
      crucial for the embryonic implantation. Peripheral Natural killer (pNK) cells are
      key components of immune systems and their activities could be regulated by sex
      hormones. In the present study we investigated the effects of estrogen
      fluctuation on the number of NK cells in vivo during the early follicular and
      middle luteal phase of menstrual cycle. In 63 healthy women with at least one
      full term pregnancy and regular menstrual cycle with duration between 24 and 32
      days, blood samples have been collected twice for investigation of CD3/CD16/CD56
      positive lymphocytes. The mean pNK count in follicular phase was 11.6% with 4.7%
      variation. The median was 10.6%. The mean pNK count in luteal phase was 12.1%
      with 5.1% variation, respectively median for cell number 11.8%. The two-tailed t
      test comparison did not find any statistical difference despite the slight
      elevation of pNK cells count in luteal phase. The insignificant variation in pNK
      cells count objected the suggestion to evaluate immunological status in women
      with adverse pregnancy outcome in specific phase of menstrual cycle.

PMID- 27025101
TI  - [LAPAROSCOPIC MYOMECTOMY WITH UTERINE ARTERY CLIPPING VERSUS CONVENTIONAL
      LAPAROSCOPIC MYOMECTOMY].
AB  - OBJECTIVE: To evaluate the differences in the intraoperative blood loss during
      laparoscopic myomectomy with or without uterine artery clipping (UAC). METHODS:
      From January 2013 to April 2015, we enrolled prospectively 119 women with
      symptomatic intramural myomas who were scheduled to undergo laparoscopic
      myomectomy (37 with UAC (study group) and 82 without (control group)). RESULTS:
      Characteristics of the myomas, operating time, duration of hospital stay and
      blood loss were comparable between the two groups. The average operating time and
      blood loss were 75 +/- 11 minutes and 100 +/- 20 ml for the experimental group
      and 60 +/- 9 minutes and 178 +/- 56 ml for the control group respectively
      statistically significant. CONCLUSION: Concurrent UAC during laparoscopic
      myomectomy reduces the intraoperative blood loss and the frequency of excessive
      bleeding. This study demonstrated the superiority of laparoscopic uterine artery
      ligation combined with myomectomy in treatment of symptomatic myomas.

PMID- 27025102
TI  - [THE VALUE OF COLPOSCOPY EXAMINATION IN DIAGNOSIS OF PRECANCEROUS AND CANCEROUS
      DISEASES OF THE CERVIX].
AB  - The aim of this study is to present the value of colposcopy examination in
      diagnosis of precancerous and cancerous diseases of the cenvix. A retrospective
      study analyze 127 patients at SA GBAL" Dr. Shterev Hospital" that undenNent,
      firstly cervical smear test and secondly a colposcopic punch biopsy The patients
      are divided in two groups--one group of cytologically non-signaled patients with
      results from the Pap test I-II and one group with cytologically -signaled
      patients with results from the Pap test III-IV The data shows a correlation
      between the cytological and histological results of the second group and absence
      of such a correlation in the first group. In the non-signaled group the mild
      precancerous lesions to Thvasive cen'ical cancer were left undiagnosed. The
      conduct of a routine colposcopy during preventive gynecological examination will
      reduce the deficiencies of the cytological method and by amplifying it, it will
      lead to better results of the diagnosis and treatment of the precanceroses and
      the cervical cancer.

PMID- 27025103
TI  - [MODELS OF CLINICAL IMPLEMENTATION OF CELL FREE FETAL DNA IN THE MATERNAL SERUM
      SCREENING TEST-ANALYSIS].
AB  - Prenatal screening by definition is a way of identifying pregnancies, with a high
      enough risk to specific fetal damage as to justify the subsequent invasive
      diagnosis among the seemingly normal pregnancies. [1] The aim of the prenatal
      screening test is to reach the high diagnostic frequency (DR > 95%), with low
      false-positive rate (FPR < 1%). Several non-invasive prenatal tests (NIPT) are
      widely adopted and use in clinical practice: 1st Trimester Combined screening
      (First trimester Combined Screening) and 2nd trimester biochemical screening
      (Second trimester biochemical screening) and in the last few years through
      screening Fetal DNA in Maternal serum (cfDNA screening). Since the introduction
      of the sfDNA test were examined and discussed the results of several ways of
      application: (1) as a primary screening method without preceding the result of
      1st trimester combined screening for chromosomal abnormalities, (2) as a
      contingent test after 1st trimester combined screening in high risk pregnancies
      (> 1:100) (3) as a contingent test after 1st trimester combined screening, when
      the calculated risk is between ( 1:10 to 1:2500). The purpose of the study: to
      compare the results of different ways of application screening through cfDNA:
      detection rate (DR) for Tri21, Tri18 and Tri13, procentage of invasive
      diagnostics and cost-effectiveness ratio of cfDNA test in comparison with the 1st
      trimester combined screening. To establish the most suitable algorithm for
      application of cfDNA test. METHODS AND MATERIALS: Analyzed were the results of
      several randomized multi-center clinical studies whose data are processed through
      a meta-analysis. RESULTS: cfDNA-test has a higher DR for Tri21 for lower FPR,
      compared to the combined screening in 1st trimester (cfDNA-DR 99%, 1st trimester
      screening-DR 96% and 0.4%FPR, respectively FPR 5%), but although it is with
      better results and reduces the incidence of invasive tests, does not justify the
      significant difference in price-performance ratio. On the other hand cfDNA-test
      is with a lower detection rate for Tri 18 or 13 (93-95%), which makes it worse
      for a primary screening test instead of combined screening in the 1st trimester.
      CONCLUSIONS: The performance of cfDNA-test in terms of the three most common
      Trisomies: 21,18 and 13 is highest when used after (contingent to) 1st trimester
      screening and only for patients with an intermediate risk from 1-st trimester
      screening (risk > 1:10 and 1:2500, around 27% of all pregnancies), as it
      increases the diagnostic rate of combined screening for Down syndrome (from 90%
      to 98%), and significantly reduces the percentage of invasive diagnostics (from
      3% to 0.7-1%) and that way we are able to achieve optimal result in price
      performance result.

PMID- 27025104
TI  - [EPIGENETIC FACTORS OF NEUROBIOLOGIC CHANGES IN FETUSES OF PREGNANT WOMEN WITH
      NEUROPSYCHIATRIC DISORDERS].
AB  - During prenatal development, the fetus is particularly vulnerable to the
      environmental harmful effects. It has been proved that the placenta is a
      significant modulator of the intrauterine environment that links maternal and
      fetal nervous systems. Emerging evidence indicates that epigenetic modifications
      prior to the birth may have substantial influence on brain development and may
      exert various neurobehavioral deficits. This review demonstrates association
      between maternal prenatal distress and depression and fetal long-term
      neurobiological and behavioral outcomes. Further investigation of the epigenetic
      dysregulation of fetal neurodevelopment may suggest new mechanisms in the
      interplay between genes and environment, and provide novel insights in the
      pathophysiology and prevention of neuropsychiatric disorders.

PMID- 27025105
TI  - [OPPORTUNITIES OF HIFU TECHNOLOGY FOR TREATMENT FIBROIDS DISEASES SUCH AS NON
      INVASIVE AND ALTERNATIVE METHOD TO SURGERY].
AB  - Concepts of medical treatment are constantly evolving and improving. This
      opportunity provides treatment with High Intensity Focused Ultrasound (HIFU). In
      Europe and Asia more than 10,000 patients with uterine fibroids have been
      successfully treated with HIFU technology until now. This is completely
      innovative technology for non-invasive extracorporeal treatment of benign and
      malignant tumors. Neighboring healthy tissue is not damaged. The main indication
      in HIFU-Center in Pleven is uterine fibroid. It is the most common solid tumor in
      the female pelvis and is the leading cause of hysterectomy. The methods of
      treatment are hysterectomy, myomectomy or embolization of uterine arteries. HIFU
      methodology allows non-invasive treatment of fibroids disease.

PMID- 27025106
TI  - [MICROSATELLITE INSTABILITY IN ENDOMETRIAL CANCER].
AB  - Microsatellite instability (MSI) is involved in the pathogenesis of about 30% of
      endometrial cancer cases. In accumulating data from the past few years MSI is
      shown to have both clinical and prognostic value. In the present work we are
      discussing the components and molecular mechanisms of functioning of the mismatch
      repair system (MMR). MSI is a hallmark of endometrial tumors with DNA MMR
      deficiency. We summarized the main pathways for accumulating mutations in coding
      and non-coding DNA sequences, which is a result of errors during replication of
      microsatellite tandem repeats. A few studies rising valuable conclusions about
      the correlation between MSI and endometrial cancer are revised.

PMID- 27025107
TI  - [VULVAR INTRAEPITHELIAL NEOPLASIA--TERMINOLOGY, SYMPTOMS AND TREATMENT].
AB  - The term vulvar intraepithelial neoplasia (VIN) was introduced for first time in
      1986 year from the International Society for the Study of Vulvar Disease (ISSVD).
      With this term are denoted precancer vulvar conditions. According to a
      classification dated 1986 depending on the degree of affection of multilayered
      squamous epithelial vulvar precancerous lesion are subdivided into three groups:
      VINI, VIN2 and VIN3. Subsequently VIN1 is determinate as a lesion which there
      isn't oncogenic potential. These types of changes often are result from
      irritation or viral infection which leads to benign condylomata acuminate.
      Compare to lesions with VIN require histological signs for high grade
      intraepithelial neoplasia as nuclear pleomorphism, increased mitotic activity,
      atypical mitotic activity and disordered architecture of squamous cells
      epithelium. These fundamental morphologic characterizations lead to revision and
      subsequent change of the current classification. In 2004 ISSVD changed the
      classification. It included lesions like VIN2 and VIN3, but they are subdivided
      in two groups: the usual type VIN and the differentiated VIN. They have different
      etiology, morphology, oncogenic potential and prognosis. The usual type VIN is
      associated with infection of high risk types of human papilloma virus and is a
      more frequently met form of VIN. A very good prognosis is characteristic for it.
      The differentiated VIN is met in postmenopausal women of about 70 with frequency
      of about 2-5%. It originated from vulvar dermatosis like lichen scierosus and
      there is a high oncogenic potential and worse prognosis. The treatment of VIN may
      be surgical and by medicines. The frequency of recurrences after treatment is 30
      50% which required frequently follows up. The aim of this literature review is to
      introduce present terminological classification of VIN, as well as basic
      clinical, diagnostically and curative methods in treat of the both types of this
      precancerous.

PMID- 27025108
TI  - [CONGENITAL UNILATERAL HYDROTHORAX--A CASE REPORT].
AB  - A case of isolated unilateral congenital hydrothorax with unknown etiology,
      graduated abortion for medical reasons in 23 weeks. The patient was later covered
      by antenatal care and during the examination one foetus with the massive right
      sided hydrothorax was found, (diagnosed by ultrasonography and NMR) The incidence
      of congenital fetal hydrothorax is estimated at approximately 1 in 15,000
      pregnancies. Early ultrasound diagnosis is of paramount importance for the
      adequate monitoring of the pregnancy and timely proof of deviation in normal
      fetal development.

PMID- 27025109
TI  - [MALIGNANT MELANOMA--THE INFLUENCE OF HORMONAL FACTORS ON THE PROGRESSION AND
      PROGNOSIS. COMPARATIVE ANALYSIS BASED ON TWO CLINICAL CASES].
AB  - Malignant melanoma is the most aggressive form of skin cancer showing extremely
      high metastatic rate and leading to high levels of lethality. The continually
      growing incidence of malignant melanoma in the world and his difficult early
      diagnosis are the occasion for numerous studies. The individual risk for
      malignant transformation of melanocytes is determined by a number of etiologic
      factors--endogenous and exogenous. Ultraviolet radiation has a leading role in
      the group of exogenous factors. Within the group of endogenous factors, besides
      the well-known photo type skin, as well as genes mutations, are added and the sex
      hormones, with their significant prognostic importance. The differences, which
      are observed in the progression and prognosis of malignant melanoma in pre- and
      postmenopausal women, and men, have defined this cutaneous neoplasma as hormone
      dependent tumor. We present two seemingly similar clinical cases of 52 year old
      woman and 53-year-old man diagnosed with malignant melanomas, developed on the
      basis of pigmented lesions located on the upper back, as we attempt a comparative
      analysis on etiopathogenetic factors led to radically different course and
      prognosis of the disease in these two patients.

PMID- 27025110
TI  - THE METAMORPHOSIS OF MEDICINE. Opportunities for Physician Leadership NOW!

PMID- 27025111
TI  - Change.

PMID- 27025112
TI  - DON'T QUIT ON YOUR SMOKERS. Persistence pays off when it comes to free nicotine
      replacement.

PMID- 27025113
TI  - Overdose Deaths in West Virginia.

PMID- 27025114
TI  - IV 3000 Dressing for Fingertip Injury: Management and Discussion.
AB  - An active, right hand dominant. 86-year-old male presented with transverse
      amputation of the right ring finger just distal to the DIP joint. Conservative
      management was recommended in order to preserve digit length, mobility, and the
      DIP joint. The IV3000 semipermeable dressing was utilized as the primary
      treatment. The clear adhesive dressing has a high moisture vapor transmission
      rate that facilitates creation of a suitable wound microenvironment. The digit
      showed significant epithelialization and mobility at two weeks post-injury and
      was healed with full range of motion at both the DIP and PIP joints by week six.
      There were no complications from use of the IV3000 dressing, and both healing
      time and pain during dressing change are improved over alternative dressings like
      gauze.

PMID- 27025115
TI  - Endovascular Repair of Lacerated Profunda Femoris Artery Using Jomed Covered
      Stent Graft.
AB  - PURPOSE: This report highlights the significance of endovascular training for
      invasive cardiologists. CASE REPORT: 78-year-old morbidly obese male with an
      inferior wall myocardial infarction underwent primary percutaneous coronary
      intervention (PCI) which was complicated by laceration of the profunda femoris
      artery. Endovascular repair of the profunda femoris artery was performed by using
      Jomed covered stents. CONCLUSION: This case report of endovascular repair of
      lacerated profunda femoris artery signifies the importance of endovascular
      training for invasive cardiologist.

PMID- 27025116
TI  - Dementia Care: Confronting Myths in Clinical Management.
AB  - Every day, patients with dementia, their families, and their physicians face the
      enormous challenges of this pervasive life-changing condition. Seeking help,
      often grasping at straws, victims, and their care providers are confronted with
      misinformation and myths when they search the internet or other sources. When
      Persons with Dementia (PWD) and their caregivers believe and/or act on false
      information, proper treatment may be delayed, and ultimately damage can be done.
      In this paper, we review commonly misunderstood issues encountered in caring for
      PWD. Our goal is to equip Primary Care Practitioners (PCPs) with accurate
      information to share with patients and families, to improve the outcomes of PWD
      to the greatest extent possible. While there are innumerable myths about dementia
      and its causes and treatments, we are going to focus on the most common false
      claims or misunderstandings which we hear in our Internal Medicine practice at
      Marshall Health. We offer suggestions for busy practitioners approaching some of
      the more common issues with patients and families in a clinic setting.

PMID- 27025117
TI  - A 6-month-old Female with Fever and Increased Head Circumference.
AB  - Brain abscesses, while a fairly rare occurrence in the pediatric population, can
      be associated with significant morbidity and mortality. Staphylococcus aureus is
      a rare cause of intracranial abscess that is generally seen in pediatric patients
      who have had traumatic injury or neurosurgical intervention. We present the case
      of a 6-month-old patient who was found to have a large brain abscess secondary to
      methicillin-sensitive Staphylococcus aureus (MSSA), despite no clear
      precipitating factors. She underwent percutaneous drainage and IV antibiotic
      treatment with gradual recovery but as-of-yet undetermined developmental
      sequelae.

PMID- 27025118
TI  - The Levator Claviculae Muscle Presenting as a Neck Mass.
AB  - The levator claviculae muscle is an uncommonly encountered muscle variant,
      occurring in 1% to 2% of the human population. Most accounts of the levator
      claviculae muscle have been reported in association with routine cadaveric
      examination and as an incidental finding by computed tomography (CT) and magnetic
      resonance (MR) imaging. We report a case of this variant muscle presenting as a
      soft-tissue mass within the neck of a young male. Furthermore, we discuss the
      embryologic origin, imaging features and clinical implication.

PMID- 27025119
TI  - Prolonged Paralysis Following Emergent Cesarean Section with Succinylcholine
      Despite Normal Dibucaine Number.
AB  - Prolonged paralysis due to a quantitative or qualitative deficiency of
      pseudocholinesterase activity is an uncommon but known side effect of
      succinylcholine. We describe a patient who experienced prolonged paralysis
      following administration of succinylcholine for general anesthesia and
      endotracheal intubation for an emergent cesarean section despite laboratory
      evidence of normal enzyme function. The patient required mechanical ventilation
      in the intensive care unit for several hours following surgery. The patient was
      extubated following return of full muscle strength and had a good outcome. The
      enzyme responsible for the metabolism of succinylcholine, pseudocholinesterase,
      was determined to be low in quantity in this patient but was functionally normal.
      This low level, by itself, was unlikely to be solely responsible for the
      prolonged paralysis. The patient likely had an abnormal pseudocholinesterase
      enzyme variant that is undetectable by standard laboratory tests.

PMID- 27025120
TI  - A Message from the President.

PMID- 27025121
TI  - The Affordable Care Act (ACA) Upheld: What's Next for Staff Nurses, Nursing
      Leaders and the Profession?

PMID- 27025122
TI  - Executive Director's Column.

PMID- 27025123
TI  - Collaboration.

PMID- 27025124
TI  - [PROTEIN KINASE C EXPRESSION FOLLOWING REMOTE ISCHEMIC PRECONDITIONING IN CARDIAC
      SURGERY].
AB  - OBJECTIVE: To evaluate cardioprotective effects of remote ischemic
      preconditioning (RIPC) in cardiac surgery patients undergoing aortic valve
      replacement depending on the type of anesthesia and investigate the level of
      myocardial protein kinase C epsilon (PKC-epsilon) expression after RIPC. METHODS:
      In prospective randomized trial, forty eight patients aging from 50 to 75 years
      old (64 (56 ;69)) were included All patients were scheduled for aortic valve
      replacement using cardiopulmonary bypass (CPB). The patients were randomized into
      4 groups: 1) RIPC applied during propofol anesthesia (RIPC prop, n = 12), 2) RIPC
      applied during sevoflurane anesthesia (RIPC sev, n = 12), 3) propofol anesthesia
      without RIPC (CONTROL prop, n = 12), 4) sevoflurane anesthesia without RIPC
      (CONTROL sev, n = 12). There was no difference found between the groups as to the
      baseline patient's data. RIPC protocol consisted of 3 simultaneous ischemic
      episodes of both lower limbs (5 minutes) with 5-min reperfusion intervals. PKC
      epsilon expression in right atrial myocardium was assessed using Western
      blotting. Troponin I (cTnI) was estimated before anesthesia induction, after 30
      min, 6, 12, 24, 48 hours after CPB completion. Also we calculated area under
      curve of cTnI (cTnI AUC). According to nonparametric distribution, data were
      assessed by the Mann-Whitney U-test and Newman-Keuls methodfor multigroup
      comparison. p < 0.05 was considered signifcant. The data are presented as median
      (25th; 75th percentile). RESULTS: Cardioprotective effects of RIPC were observed
      only after sevoflurane anesthesia: cTnI AUC was 134,8 (122,3; 232.4) ng/ml/48 h
      in CONTROL sev group and only 74.3 (64.7; 85.0) ng/ml/48 h in RIPC sev group (p <
      0.05). RIPC applied during propofol anesthesia was not associated with cTnIAUC
      decrease: 93.8 (74.1; 246.8) ng/ml/48 h in CONTROL prop group and 122.5 (74.1;
      185.0) ng/ml/48 h in RIPC prop group (p = 0.37). RIPC applied during sevoflurane
      anesthesia significantly increased PKC-epsilon expression: 1221 (921; 1438) U in
      CONTROL sev group vs 1882 (1564; 2131) U in RIPC sev group 6 (p < 0.05). RIPC
      implication during propofol anesthesia was not associated with any significant
      difference in PKC-epsilon expression in comparison with control group: 620 (436;
      782) U in CONTROL prop group versus 788 (574;1063) U in RIPC prop group. In
      control groups, PKC-epsilon expression was significantly higher in sevoflurane
      anesthesia in comparison with propofol anesthesia. CONCLUSION: RIPC was only
      effective when it was applied during sevofiurane anesthesia. This was confirmed
      by PKC-epsilon expression increase and lower value of cTnI. There were no
      evidence of preconditioning and cardioprotection when MPG was initiated during
      propofol anesthesia.

PMID- 27025125
TI  - [EFFICACY AND SAFETY OF LUNG RECRUITMENT MANEUVER IN PATIENTS WITH DIFFERENT
      PERIPHERAL CHEMOREFLEX SENSITIVITY].
AB  - BACKGROUND: The concept of open lungs, which includes a maintaining of positive
      end-expiratory pressure (PEEP) and lung recruitment maneuver (LRM), proven in the
      prevention of atelectasis occurring during anesthesia with mechanical ventilation
      (MV). However, it adversely affects the central hemodynamics, and can increase
      the incidence of perioperative complications, especially in elderly patients. The
      sensitivity of the peripheral chemoreflex (SPCR) is a marker of disturbed
      neuroreflex regulation of the cardiorespiratory system. The aim of the study was
      to evaluate the influence of LRM on the cardiorespiratory system in patients with
      different SPCR. Methods: The study was conducted in 85 elderly patients which
      were undergone abdominal surgery under general anesthesia and mechanical
      ventilation with LRM and the subsequent maintenance of PEEP The patients were
      divided into two groups, according to the SPCR level determined using Shtange
      test: Group B had a high SPCR (n = 35); Group C--the middle SPCR (n = 50).
      RESULTS: The respiratory system compliance and arterial blood oxygenation were
      increased and airway resistance was decreased in both groups. LRM led to a
      decrease in cardiac index in both groups, but in the group C this decrease was
      offset by an increase in peripheral vascular resistance, which did not occur in
      Group B. The observed changes in Group B have caused a more frequent hypotension,
      use ofvasopressors and infusion. CONCLUSION: LRM improves oxygenation and
      biomechanical properties of the respiratory system. In patients with impaired
      reflex regulation of the cardiorespiratory system LRM increases the risk of
      hemodynamic disturbances.

PMID- 27025126
TI  - [CHARACTERISTICS OF SURFACE ELECTROMYOGRAPHY AND ACID-BASE BALANCE IN PATIENTS
      WITH INTENSIVE CARE UNIT-ACQUIRED WEAKNESS].
AB  - OBJECTIVE: The study was aimed to search for correlation between parameters of
      surface electromyography and acid-base balance (ABB) in patients with intensive
      care unit-acquired weakness (ICUAW, n = 29, duration 7-180 days). METHODS: The
      linear and nonlinear parameters of sEMG (mean frequency of spectrum, fractal and
      correlation dimension, correlation entropy) and ABB and their correlation
      coefficient with bed rest (BR) and duration of mechanical ventilation (MT) were
      computed. RESULTS: Here we report that in first 40 days sEMG parameters were
      indicative of the neurogenic process in the skeletal muscle, while within 41-100
      days signs of the myogenic pathology were documented. The ABB parameters
      statistically signIficantly correlated with BR and MV duration. CONCLUSION: ICUAW
      exerts effect on the skeletal muscle. Within first 40 days this effect is
      actuated in a form of neuropathy, while further it has signs of myopathy. We
      argue that MV duration appear to be a pathogenic factor in these modifications.

PMID- 27025127
TI  - [ANATOMICAL AND PHYSIOLOGICAL JUSTIFICATION OF ENTERAL OXYGENOTHERAPY].
AB  - The article extensively covers the historical stages of the development of
      enteral oxygenation technique. There is shown the long way of scientific research
      from the first using of "oxygenating" products in the early XX century to
      undertaken hundred years after attempts of the oxygen introduction into
      gastrointestinal tract for systemic oxygenation improvement and prevention of
      intestinal flora translocation in sepsis. On the basis of anatomical and
      physiological characteristics of the intestinal wall there was shown the
      possibility of both local and systemic effects of the oxygen introduced into the
      intestinal tract. The hypothesis about the possibility of improving homeostasis
      and pulmonary gas exchange by normalizing the functioning of the gastrointestinal
      tract was presented.

PMID- 27025128
TI  - [GOAL-DIRECTED FLUID THERAPY IN SEVERE CONCOMITANT TRAUMA].
AB  - METHODS: We examined 78 patients with severe concomitant injury. Were evaluated
      the severity of the injury and indices of volumetric haemodynamic monitoring by
      PICCO. The retrospective comparison group consisted of 50 patients with severe
      concomitant injury who were treated in the ICU of Trauma Institution during 2009
      2011. RESULTS: In patients with severe concomitant injury goal-directed fluid
      therapy based on PICCO monitoring parameters increasing the volume of infusion on
      the second and third post-traumatic days by 45% and 24%, respectively (< 0.05).
      Infusion-related pulmonary complications in the study group patients were not
      recorded Goal-directed fluid therapy was one of the factors that made it possible
      to reduce patient's mortality 2.1 times on conditions that severity of the injury
      and the initial state were similar. Colloid (6% HES 200/0.5) infusion was
      associated with increases in rate of transient azotemia.

PMID- 27025129
TI  - [PLACE REMAXOL AS A HEPATOPROTECTOR IN INTENSIVE THERAPY OF PERVASIVE
      PERITONITIS].
AB  - PERPOSE OF RESEARCH: to evaluate the effectiveness of Remaxol in patients with
      pervasive peritonitis. MATERIALS AND METHODS: assessed the effectiveness of a
      balanced infusion of the drug (Remaxol) in the treatment of 44 patients agedfrom
      18 to 50 years. Patients were devided into 2 groups by the method of envelopes.
      All patients received a comprehensive differential therapy: 21 patient 1 group
      consisting of infusion therapy in the postoperative period received Remaxol at a
      dose of 800 mg/day for 7 days. RESULTS: the comporative assessment of indicators
      of systemic hemodinamics, oxygen transport, asid base status, glucose, lactose
      and free radical oxydation. Patients on the first background was used Remaxol
      have experiensed a more rapid relief of metabolic disorders, endotoxemia and
      hepatic dysfunction compared with the indices of the 2 group patients. Noted
      earlier stabilization of rudicators of systemic hemodynamics and oxygen
      transport. This has reduced the duration of respiratory and vasopressor suppot,
      early start ofparenteral intreduction in case the power (p < 0.05). CONCLUSIONS:
      this study shows that use of the drug for the purpose of relief Remaxol hepatic
      dysfunction and prevention of drug liver toxicity in conditions ofperitonitis,
      after 48 hours of operation, provides a positive dynamics and stabilization
      ofparameters of central hemodynamics, contributing to the abolition of
      vasopressor support, and contributes to the effective utilization of oxygen,
      while providing antioxidant effect.

PMID- 27025130
TI  - [EFFICIENCY OF SEROTONIN ADIPINATE IN INTESTINAL DYSFUNCTION IN PATIENTS AFTER
      COLORECTAL OPERATIONS].
AB  - We performed a retrospective analysis of case histories of acute colonic
      obstruction due to colon cancer A total of 291 patients were divided on two
      groups: 1--a control group (patients presenting risk of developing intestinal
      dysfunction with 'basic' therapy, n = 123); 2--the comparison group (n = 57)
      represented patients who were taken to optimize the post-operative period with
      the inclusion in the scheme of the basic treatment of serotonin adipinate. The
      use of serotonin adipinatein treatment of intestinal dysfunction allows fully
      restore bowel motility to 3rd day.

PMID- 27025132
TI  - [STAGES OF OPIOID THERAPY OF CHRONIC PAIN IN RUSSIA: ANCIENT AND COMING].
AB  - There is history of the introduction and development of systemic and invasive
      opioid treatment of chronic cancer pain in Russia presented by the authors-
      experts with experience in thisfield over 30 years. The earliest researchers are
      no more among us, but their memory is still alive in the publications of the
      early 1980's. Along with the analysis of accumulated by Russian specialists
      positive clinical experience of opioids using, authors discuss main problems of
      organization and availability of adequate opioid therapy of chronic pain in
      Russia. Ways of further development ofpalliative care and pain management in
      oncology is discussed as well as.

PMID- 27025131
TI  - [GENDER DIFFERENCES OF THE HEMOSTASIS POSTAGRESSIVE EARLY RESPONSE IN ACUTE
      NECROTIZING PANCREATITIS].
AB  - The study was performed in a group of 25 patients with acute necrotizing
      pancreatitis (mean age 46.2 +/- 6.74 years). Gender differences of the hemostasis
      postagressive early response in the early stages of the disease were identified
      by comparing the procoagulant , anticoagulant and fibrinolytic blood activity of
      men and women suffering from pancreatitis. Compared to men, women showed higher
      concentrations of fibrinogen, D-dimer and VWF and smaller values marked
      trombokrit , antithrombin III, inhibitor of plasmin and protein C (p < 0.05).
      These results suggest a greater tendency to thrombi formation in women with acute
      pancreatitis; We believe that gender differences should be the subject of further
      research.

PMID- 27025133
TI  - [OPIOID-FREE ANESTHESIA, ANALGESIA AND SEDATION IN SURGERY OF HEAD AND NECK
      TUMOR].
AB  - 62 adult patients had highly traumatic cancer head and neck surgery under
      multimodal non-opioid general anesthesia consisted of dexmedetomidine, lidocane,
      nefopam and sevoflurane. 18 patients had been intubatedwith fiber optic
      bronchoscope because of II-IV grade trismus. 10 patients with laryngeal stenosis
      had been tracheotomizedfor intubation. All these 28 patients had been sedated
      with dexmedetomidine, lidocane and small doses (10-20 mg) ketamine additionally
      to local anesthesia. All these patients maintained consciousness and breathed
      spontaneously. Propofol and rocuronium preceded tracheal intubation. I.V.
      infusion of dexmedetomidine and lidocane proceeded additionally to sevoflurane (1
      1.5MAC) .during the main surgery procedure course. All 62 cases went and finished
      uneventfully. Awakening and spontaneous breathing recovered just after the end of
      the surgery. During two first postoperative days all the patients had persistent
      i.v. analgesia with 1% lidocaine, nefopam and tenoxycam. On the day. 3 analgesia
      proceeded with nefopam and tenoxycam i.m. The quality of analgesia was good, with
      no complications. Only 3 patients had one promedol (trimeperidine) or tramadol
      iniection at the start-up of this new method of analgesia.

PMID- 27025134
TI  - [PERIOPERATIVE EPIDURAL ANALGESIA IN LUNG SURGERY IN LOW FUNCTIONAL RESPIRATORY
      RESERVE PATIENTS].
AB  - It is now proven that the use of thoracic epidural blockage in thoracic surgery
      results in a significant reduction in the incidence of pulmonary infection,
      reduces the duration of postoperative mechanical ventilation and length of stay
      in the ICU. Moreover, the epidural analgesia is the most effective way of pain
      relief which is especially important after lung operations. Finding the most
      optimal variant of the method has drawn attention to a procedure based on the use
      of small doses of local anesthetic (ropivacaine), opioid (fentanyl) and
      epinephrine, as proposed by the Norwegian anesthesiologists Breivik and Niemi.
      Reducing the depth of the epidural block may be offset by the use of a powerful
      general anesthetic sevoflurane. In this way, implementing the principle of
      multimodal anesthesia, involves the use of a rational combination of low doses of
      unidirectional components with different mechanisms of action and levels. In our
      work, we have once again demonstrated that perioperative epidural analgesia is
      one of the essential components of secure anesthesia, especially in patients with
      reduced functional reserves.

PMID- 27025135
TI  - [PREEMPTIVE ANALGESIA AS PART OF MULTICOMPONENT ANESTHESIA IN CHILDREN WITH
      OPERATIONS IN THE NASAL CAVITY AND NASOPHARYNX].
AB  - OBJECTIVE: The article presents the results of assessing the impact of pre
      emptive analgesia with lidocaine and paracetamol compared withfentanyl for
      postoperative pain in children undergoing surgery for nasal cavity and
      nasopharynx. METHODS: We evaluated the incidence and severity ofpostoperative
      pain in 150 patients aged 3 to 17 years (ASA I-II), following operations in the
      nasal cavity and nasopharynx. RESULTS: In pre-emptive analgesia group, patients
      (n = 75) experienced postoperative pain at 28% less in comparison with the
      control group. The severity ofpain was observed at 50% less in the intervention
      group which was accompanied by lower levels of cortisol. Additional analgesia
      during the first 2 hours after surgery there was within 15% less in a pre-emptive
      analgesia group when compared to the control group. Patients with multi-component
      of general anesthesia and local anesthetic lidocaine via a nebulizer and
      paracetamol i. v. were ready for extubation/removal of the laryngeal mask at 40%
      earlier; andfor transfer to the general department 50% sooner than patient with
      combined anesthesia with sevoflurane, nitrous oxide and fentanyl.

PMID- 27025136
TI  - [POSSIBILITY OF CORRECTION OF METABOLIC DISORDERS WITH REAMBERIN IN ACUTE PERIOD
      OF TRAUMATIC INJURY].
AB  - 56 patients at the age of 18-60 years with severe trauma were examined. Influence
      of the polyelectrolytic (Reamberin)solution on an acid-base state, osmolarity and
      electrolytic composition of plasma in the acute posttraumatic period was
      evaluated. It was found that patients, who was treated by isotonic sodium
      chloride solution and Ringer's solution, had metabolic acidosis and
      hyperchloremia. In contrast, in the reamberin group 82% of patients had lower
      concentrations of chloride and had nothing acid-base disturbances on the second
      day after trauma. Reamberin didn't influence on plasma osmolarity and the rate of
      metabolic alkalosis during the acute period of a trauma.

PMID- 27025137
TI  - [COMPARATIVE STUDY OF THE TACTICS OF SURGICAL FIXATION WITH THE CLOSED INJURY OF
      THE CHEST: THE VIEW OF THE RESUSCITATOR, ECONOMIC ASPECTS].
AB  - The closed injury of chest with the breaks of edges is the vital problem of
      traumatology, anesthesiology and resuscitation For the change to conservative
      treatment with the aid of mechanical ventilation of lungs today come the methods
      of surgical fixation with the closed injury of chest. The conducted investigation
      showed the clinical and economic expediency of introducing the method of active
      surgical tactics.

PMID- 27025138
TI  - [NEW TECHNIQUE OF SPINAL ANESTHESIA WITH EPIDURAL VOLUME EXTENSION FOR CAESAREN
      SECTION IN PREGNANT WOMEN WITH CONCOMITANT CARDIAC PATHOLOGY].
AB  - BACKGROUND: Spinal anesthesia with the epidural volume extension provides the
      possibility of using small doses of local anesthetics and the low frequency of
      hypotension. However, the dose of the local anesthetic and the volume of normal
      saline for administration into the epidural space, remain unclear. OBJECTIVE: To
      study the influence of new techniques of spinal anesthesia with the epidural
      volume extension at the level of sensory block and hemodynamic in pregnant with
      concomitant cardiac pathology during cesarean section. METHODS: In an
      observational study were included 24 pregnant women with cardiac pathology. Women
      were divided into 3 groups, depending on the value of intra-abdominal pressure
      (lAP). Expansion of the epidural space was performed before spinal anesthesia.
      For spinal anesthesia we used heavy bupivacaine 0.5% (5.5 +/- 0.1 mg). The volume
      of saline for administration into the epidural space depends on the level of lAP
      RESULTS: The average upper level of sensory block did not difer significantly in
      groups and amounted Th 2.1 +/- 0.5, 95% C.I. 1.6-4.0 (p = 0.001). The only one
      woman in group 3 (4.1%) developed hypotension. The maximum level of motor block
      (Bromage score) among the groups was similar and amounted to 1.5 +/- 0.2, 95%
      C.I. 1.0-2.0 (p < 0.001). CONCLUSIONS: The new technique of spinal anesthesia
      with the epidural extension provides qualitative analgesia and stable
      hemodynamics in pregnant women with concomitant cardiac pathology

PMID- 27025139
TI  - [A CASE OF SEVERE AMLODIPINE POISONING].
AB  - The article is devoted to the actual problem--poisoning by calcium channel
      blockers. The case of the departure of the patient amlodipine, clinical picture,
      treatment and its effectiveness. In the discussion described pharmacological
      characteristics of the group of calcium channel blockers, mechanisms of
      development syndromes developing in this type of shipment and pathogenetic
      approach to therapy.

PMID- 27025140
TI  - [VOLEMIC STATUS AND THE PHASIC APPROACH TO THE TREATMENT OF CRITICAL STATES--NEW
      OPPORTUNITES AND PROSPECTS].
AB  - Current guidelines suggest that an early and aggressive fluid therapy is the best
      rescue approach to restore and preserve cardiac index, organ function and
      decrease the risk of multiple organ failure in shock of various origin. However,
      escala- tion of fluid resuscitation is a double-edged sword often associated with
      reperfusion, glicocalyx injury, capillary leakage, delayed weight gain and
      heperhydration. The body of evidences demons trates that an excessive fluid load
      in ICUpatient with global increased permeability syndrome, and, particularly, in
      ARDS and acute kidney injury can be devastating, particularly when guided with
      central venous pressure. This important therapeutical conflict highlights the
      importance of the emerging concept of "phasic "fluid management and physiologic
      monitoring. The type and volume of the fluid should be thoroughly selected in
      accordance with the phase of shock, risk of impending organ dysfunction and
      individual co-morbidity. The phasic approach, along with individualized early and
      delayed goal-directed protocols might fasten the resolution of organ dysfunction,
      reduce the duration of shock and mechanical ventilation and improve the outcomes.

PMID- 27025141
TI  - [EFFECTS OF XENON ANESTHESIA ON HEMODYNAMICS: WHAT DO WE KNOW UNTIL 2015?
      (REVIEW)].
AB  - Xenon is known as an anesthetic in many ways closer to the ideal. In recent
      years, despite a number of objective reasons limiting its widespread use, the
      search continues for understanding how xenon influences on central hemodynamic
      parameters and regional blood flow. Analysis of several dozen of modern articles
      revealed many differences between the earlier and present data, emphasizing the
      prospect offurther research. According to Russian authors Xe has a positive
      inotropic effect on the myocardium and increases cardiac output. Foreign
      researchers in animal experiments notice vasoconstrictor properties of Xe with
      increased vascular resistance in the systemic and pulmonary circulation. The
      place of Xe as an anesthetic in the anesthetist's arsenal yet to be seen.

PMID- 27025142
TI  - [CENTRAL ANTICHOLINERGIC... SYNDROME?].
AB  - While reading special literature in diferent languages the authors noted
      surprising fact: the term and concept of "central anticholinergic syndrome" is
      well-known as common anaesthesia complication in German (abbr: ZAS) and partially
      Spanish sources, but in Russian, English or French literature is used only in
      toxicological context. Describing etiology, pathogenesis, symptoms, diagnosis and
      treatment of the complication manifesting with comatose, agitated or shivering
      forms, the authors analyzing the reasons for such a noticeably diferent
      approaches to the situation reaching 10% of all the general anaesthesia cases.
      Probably, ZAS isn't nosologically clearly defined syndrome, but just adverse
      appearance of one of the fundamental general anaesthesia mechanisms? Anyway, the
      problem of central cholinergic activity suppression, excessive by its amplitude
      and/or duration, exists all over the world. German concept of ZAS allows the
      anaesthesiologist to resolve it on pathogenically generalized basis, while in
      other professional communities various symptomatic approaches seem to be more
      common.

PMID- 27025143
TI  - Pediatric Nephrology Nursing--A Very Special Specialty.

PMID- 27025144
TI  - Nephrology Nursing Across the Life Span.

PMID- 27025145
TI  - Health Literacy: Perceptions and Experiences of Pediatric Nephrology
      Interprofessional Team Members.
AB  - Health literacy is an important factor in health care quality. This study
      examined health literacy perception and health literacy experience of a
      convenience sample of pediatric nephrology interprofessional team members.
      Results indicated that the majority of pediatric nephrology interprofessional
      team members understand the need for health literacy and want to learn about
      health literacy, but have limited experience with health literacy. This study
      provides knowledge that can be used to develop, promote, and enhance best
      practices related to health literacy among pediatric nephrology interprofessional
      team members.

PMID- 27025146
TI  - Camps and Their Benefit to Pediatric Nephrology Patients.
AB  - Children with end stage renal disease (ESRD) frequently miss great amounts of
      school due to hospitalizations and three-times-a week hemodialysis (if that is
      their modality); thus, they miss opportunities to be with their peers and learn
      normal social interactions with other students. Because of this lack of normal
      socialization, many children with ESRD are behind in development in contrast to
      their peers and need opportunities to enhance their growth and development. One
      way this can occur for children with ESRD is by providing them opportunities to
      attend age-appropriate and disease-appropriate camps.

PMID- 27025147
TI  - Increasing Vaccination Rates in a Pediatric Chronic Hemodialysis Unit.
AB  - Children with chronic kidney disease (CKD) are at an increased risk for serious
      complications from vaccine-preventable childhood diseases. Despite this risk,
      vaccination rates remain low. The barriers to vaccination in the pediatric
      population on dialysis are multifactorial. The advanced practice registered nurse
      (APRN) is well poised to serve as a wellness champion for this chronic
      population. This article chronicles an APRN-led quality improvement project to
      increase vaccination rates to 100% in an outpatient pediatric population on
      hemodialysis. A quality improvement system was created to systematically review
      immunizations upon admission to the hemodialysis unit and annually thereafter.
      Over a two-year period, immunization rates improved significantly.

PMID- 27025148
TI  - Pediatric Renal Transplantation.
AB  - Pediatric patients with end stage renal disease (ESRD) are not as prevalent as
      adults with ESRD, but the numbers are increasing each year. Medical management is
      the same for pediatric patients as it is with adults with ESRD: hemodialysis,
      peritoneal dialysis, no therapy, or transplantation. Among most pediatric
      nephrology centers, the goal for patients is to achieve transplantation.

PMID- 27025149
TI  - Development of Online Learning Modules as an Adjunct to Skills Fairs and Lectures
      to Maintain Nurses' Competency and Comfort Level When Caring for Pediatric
      Patients Requiring Continuous Renal Replacement Therapy (CRRT).
AB  - Continuous renal replacement therapy (CRRT) for pediatric patients is an
      extremely specialized therapy requiring knowledge of the patient's diagnosis,
      understanding of the principles of the therapy, astute patient assessment, and
      proficiency with complicated equipment. The complexity of CRRT is compounded by
      its relatively rare occurrence, in the pediatric population. Maintaining staff
      competency with this high-risk/low-volume therapy is extremely difficult. This
      article discusses the development and implementation of a structured system and
      set of resources to support routine education, and the development of two online,
      interactive learning modules to provide additional exposure to GRRT throughout
      the year. The modules are an efficient, effective, and inexpensive way to provide
      additional education and information to large groups of staff.

PMID- 27025150
TI  - What Is 'Normal?' Evaluating Vital Signs.
AB  - PROBLEM: Vital sign (VS) assessment and monitoring are often routinely scheduled
      whether they are needed or not. This practice led pediatric nurse leaders to
      voice concerns about the frequenty of VS at a National Summit for Pediatric and
      Adolescent Evidence-Based Practice. A search of databases yielded no direct
      evidence regarding frequency. However, we determined that before this question
      could be adequately addressed, we first needed answers to two other important
      questions concerning normative values for this population and what constitutes
      significant change in VS. CLINICAL QUESTIONS: Among pediatric patients 1 to 5
      years of age, 1) what are "normal" VS parameters, and 2) what is a significant
      change in VS? METHOD: Additional searches, including a hand search, yielded five
      systematic reviews, one case-control study, five descriptive studies, and eight
      textbooks on normative values for children. Additionally, six articles on
      pediatric early warning signs (PEWS) were also reviewed. FINDINGS: Systematic
      reviews agree that vital signs are ill-defined and are a poor indicator of
      physical deterioration in young children. Normative VS tables are inconsistent
      and sometimes contradictory. Change parameters in the PEWS literature also lacked
      consistency. There is scarcity of high-quality, consistent research on normative
      VS values for children. Additionally, there is a lack of evidence to guide the
      frequency of assessments and use of behavioral and physiologic indicators of
      decline in young hospitalized children. This points to opportunities for further
      research in these areas. Clinicians need VS guidelines based on research to guide
      their clinical decision making and interventions.

PMID- 27025151
TI  - Validation: A Family-Centered Communication Skill.
AB  - Family-centered care can seem challenging when family member behavior, choices,
      attitudes, or emotions are "difficult" or "challenging" to deal with. Yet nurses
      can develop skills to effectively interact with families in a wide variety of
      circumstances and then become able to practice family-centered care in any
      situation that might arise. One particularly useful skill is "validation," which
      means accepting what the family member says or does as a valid expression of
      thoughts and feelings in that particular circumstance at that particular time.
      Validation does not mean there is agreement or acceptance of unsafe behaviors,
      only that the nurse acknowledges that the family member's concerns and feelings
      are important and should be listened to and taken seriously, even in the presence
      of disagreement. Validation, which should be individualized, can take many forms,
      ranging from providing complete attention to reflection of statements,
      identification of possible unexpressed emotions, normalization, and finally, a
      full and genuine sense of connection. Understanding and practicing validation can
      empower nurses and family members, as well as support effectivefamily-centered
      communication and problem solving even in challenging circumstances.

PMID- 27025152
TI  - Children and Adolescents with Chronic Kidney Disease: A Population at Risk for
      More Than Just Kidney Disease.
AB  - Health-related quality of life (HRQOL) of children and adolescents with chronic
      health conditions is a multifactorial concept that combines a child's perception
      and adaptation to physical, social, emotional, and school environments regardless
      of particular medical diagnosis. Children with chronic kidney disease (CKD)
      experience non-kidney specific co-morbidities, including depression, body image
      alterations, and sleep disturbance, that impair their daily lives. This article
      reviews the pediatric nephrology literature to highlight the evidence identifying
      these riskr to HRQOL and suggesting ways in which nurses in both nephrology and
      primary care are poised to identify and modify these risk factors.

PMID- 27025153
TI  - Convergent and Modular Synthesis of Candidate Precolibactins. Structural Revision
      of Precolibactin A.
AB  - The colibactins are hybrid polyketide-nonribosomal peptide natural products
      produced by certain strains of commensal and extraintestinal pathogenic
      Escherichia coli. The metabolites are encoded by the clb gene cluster as prodrugs
      termed precolibactins. clb(+) E. coli induce DNA double-strand breaks in
      mammalian cells in vitro and in vivo and are found in 55-67% of colorectal cancer
      patients, suggesting that mature colibactins could initiate tumorigenesis.
      However, elucidation of their structures has been an arduous task as the
      metabolites are obtained in vanishingly small quantities (MUg/L) from bacterial
      cultures and are believed to be unstable. Herein we describe a flexible and
      convergent synthetic route to prepare advanced precolibactins and derivatives.
      The synthesis proceeds by late-stage union of two complex precursors (e.g., 28 +
      17 -> 29a, 90%) followed by a base-induced double dehydrative cascade reaction to
      form two rings of the targets (e.g., 29a -> 30a, 79%). The sequence has provided
      quantities of advanced candidate precolibactins that exceed those obtained by
      fermentation, and is envisioned to be readily scaled. These studies have guided a
      structural revision of the predicted metabolite precolibactin A (from 5a or 5b to
      7) and have confirmed the structures of the isolated metabolites precolibactins B
      (3) and C (6). Synthetic precolibactin C (6) was converted to N-myristoyl-d
      asparagine and its corresponding colibactin by colibactin peptidase ClbP. The
      synthetic strategy outlined herein will facilitate mechanism of action and
      structure-function studies of these fascinating metabolites, and is envisioned to
      accommodate the synthesis of additional (pre)colibactins as they are isolated.

PMID- 27025155
TI  - Ice-shell purification of ice-binding proteins.
AB  - Ice-affinity purification is a simple and efficient method of purifying to
      homogeneity both natural and recombinant ice-binding proteins. The purification
      involves the incorporation of ice-binding proteins into slowly-growing ice and
      the exclusion of other proteins and solutes. In previous approaches, the ice was
      grown around a hollow brass finger through which coolant was circulated. We
      describe here an easily-constructed apparatus that employs ice affinity
      purification that not only shortens the time for purification from 1-2 days to 1
      2 h, but also enhances yield and purity. In this apparatus, the surface area for
      the separation was increased by extracting the ice-binding proteins into an ice
      shell formed inside a rotating round-bottom flask partially submerged in a sub
      zero bath. In principle, any ice-binding compound can be recovered from liquid
      solution, and the method is readily scalable.

PMID- 27025154
TI  - Substrate complexes of human dipeptidyl peptidase III reveal the mechanism of
      enzyme inhibition.
AB  - Human dipeptidyl-peptidase III (hDPP III) is a zinc-dependent hydrolase cleaving
      dipeptides off the N-termini of various bioactive peptides. Thus, the enzyme is
      likely involved in a number of physiological processes such as nociception and is
      also implicated in several forms of cancer. We present high-resolution crystal
      structures of hDPP III in complex with opioid peptides (Met-and Leu-enkephalin,
      endomorphin-2) as well as with angiotensin-II and the peptide inhibitor IVYPW.
      These structures confirm the previously reported large conformational change of
      the enzyme upon ligand binding and show that the structure of the closed
      conformation is independent of the nature of the bound peptide. The overall
      peptide-binding mode is also conserved ensuring the correct positioning of the
      scissile peptide bond with respect to the catalytic zinc ion. The structure of
      the angiotensin-II complex shows, how longer peptides are accommodated in the
      binding cleft of hDPP III. Differences in the binding modes allow a distinction
      between real substrates and inhibitory peptides or "slow" substrates. The latter
      displace a zinc bound water molecule necessitating the energetically much less
      favoured anhydride mechanism as opposed to the favoured promoted-water mechanism.
      The structural data also form the necessary framework for the design of specific
      hDPP III inhibitors. 

PMID- 27025156
TI  - The Thioredoxin Encoded by the Rod-Derived Cone Viability Factor Gene Protects
      Cone Photoreceptors Against Oxidative Stress.
AB  - AIMS: Rod-derived cone viability factor long (RdCVFL) is an enzymatically active
      thioredoxin encoded by the nucleoredoxin-like-1 (Nxnl1) gene. The second product
      of the gene, RdCVF, made by alternative splicing is a novel trophic factor
      secreted by rods that protects cones in rodent models of retinitis pigmentosa,
      the most prevalent inherited retinal disease. It acts on cones by stimulating
      aerobic glycolysis through its interaction with a complex containing basigin-1
      and the glucose transporter GLUT1. We studied the role of Nxnl1 in cones after
      its homologous recombination using a transgenic line expressing Cre recombinase
      under the control of a cone opsin promoter. RESULTS: We show that the cones of
      these mice are dysfunctional and degenerate by 8 months of age. The age-related
      deficit in cones is exacerbated in young animals by exposure to high level of
      oxygen. In agreement with this phenotype, we found that the cones express only
      one of the two Nxnl1 gene products, the thioredoxin RdCVFL. Administration of
      RdCVFL to the mouse carrying a deletion of the Nxnl1 gene in cones reduces the
      damage produced by oxidative stress. Silencing the expression of RdCVFL in cone
      enriched culture reduces cell viability, showing that RdCVFL is a cell-autonomous
      mechanism of protection. INNOVATION: This novel mode of action is certainly
      relevant for the therapy of retinitis pigmentosa since the delivery into cones of
      the rd10 mouse, a recessive model of the disease, rescues cones. CONCLUSION: Our
      work highlights the duality of the Nxnl1 gene, which protects the cones by two
      distinct mechanisms. Antioxid. Redox Signal. 24, 909-923.

PMID- 27025158
TI  - Crystalline-like structures and multilayering in Langmuir films of ionic liquids
      at the air-water interface.
AB  - Langmuir films of [C18mim][NTf2] ionic liquid exhibited, for the first time, the
      reversible formation of crystalline-like structures at the surface of water,
      compatible with the formation of multilayers. Atomistic molecular dynamics
      simulation results support the experimental findings, unambiguously indicating
      the existence of a trilayer. 

PMID- 27025157
TI  - Bisphenol A, an environmental estrogen-like toxic chemical, induces cardiac
      fibrosis by activating the ERK1/2 pathway.
AB  - Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical. The
      present study aimed to verify whether BPA could induce proliferation of cardiac
      fibroblasts and collagen production leading to cardiac interstitial fibrosis.
      After exposure to BPA for 30 consecutive days, decreased cardiac function was
      observed in rats using echocardiography, and the deposition of collagen was
      detected by Masson's trichrome staining and electron microscope. BPA remarkably
      stimulated proliferation and migration of cultured cardiac fibroblasts and
      collagen production in a concentration-dependent manner, as revealed by MTT,
      wound healing assay and collagen assay. Meanwhile, BPA treatment also enhanced
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In
      contrast, pretreatment with estrogen receptor inhibitor ICI182780 or ERK
      inhibitor PD98059 prevented the enhanced phosphorylation of ERK1/2, and
      subsequently inhibited the up-regulation of transforming growth factor-beta1 (TGF
      beta1) expression induced by BPA. As a consequence, these inhibitors also
      decreased proliferation and collagen production, as well as the fibrosis-related
      genes expression. Taken together, our results indicated that BPA may act as a
      promoting factor in proliferative process and collagen production of cardiac
      fibroblasts via activating ERK1/2. 

PMID- 27025159
TI  - Three-dimensional structural dynamics and fluctuations of DNA-nanogold conjugates
      by individual-particle electron tomography.
AB  - DNA base pairing has been used for many years to direct the arrangement of
      inorganic nanocrystals into small groupings and arrays with tailored optical and
      electrical properties. The control of DNA-mediated assembly depends crucially on
      a better understanding of three-dimensional structure of DNA-nanocrystal
      hybridized building blocks. Existing techniques do not allow for structural
      determination of these flexible and heterogeneous samples. Here we report cryo
      electron microscopy and negative-staining electron tomography approaches to
      image, and three-dimensionally reconstruct a single DNA-nanogold conjugate, an 84
      bp double-stranded DNA with two 5-nm nanogold particles for potential substrates
      in plasmon-coupling experiments. By individual-particle electron tomography
      reconstruction, we obtain 14 density maps at ~2-nm resolution. Using these maps
      as constraints, we derive 14 conformations of dsDNA by molecular dynamics
      simulations. The conformational variation is consistent with that from liquid
      solution, suggesting that individual-particle electron tomography could be an
      expected approach to study DNA-assembling and flexible protein structure and
      dynamics. 

PMID- 27025160
TI  - VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK
      0683) in Combination With Bortezomib in Patients With Relapsed and Refractory
      Multiple Myeloma.
AB  - BACKGROUND: The present global, open-label, single-arm, multicenter, phase IIb
      study was designed to determine the efficacy and tolerability of oral vorinostat
      combined with standard doses of bortezomib in patients with multiple myeloma
      considered refractory to novel myeloma agents. PATIENTS AND METHODS: Eligible
      patients were age >= 18 years, had received >= 2 previous regimens, had disease
      refractory to >= 1 previous bortezomib-containing regimen, and had received >= 1
      dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The
      patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days
      1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral
      dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib
      could be added for patients with progressive disease after 2 cycles or no change
      after 4 cycles. The primary endpoint was the objective response rate. RESULTS:
      The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and
      the median duration of response was 211 days (range, 64-550 days). The median
      overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4
      months), with a 2-year survival rate of 32%. The frequently reported adverse
      events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia
      (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that
      of bortezomib and vorinostat. CONCLUSION: The combination of vorinostat and
      bortezomib is active in patients with multiple myeloma refractory to novel
      treatment modalities and offers a new therapeutic option for this difficult-to
      treat patient population (ClinicalTrials.gov identifier, NCT00773838).

PMID- 27025162
TI  - The softer (and furrier) side of oncology.

PMID- 27025163
TI  - A pan-Canadian survey of peer review practices in radiation oncology.
AB  - PURPOSE: Peer review (PR) of treatment plans has been recognized internationally
      as a key component of quality care in radiation oncology programs (ROPs). We
      conducted a survey of Canadian ROPs to describe current PR practices and identify
      barriers/facilitators to PR optimization. METHODS AND MATERIALS: A 42-item e
      survey was sent to all Canadian ROPs (n = 44). Survey development was guided by
      expert consensus, literature review, and existing guidelines. One
      multidisciplinary response per ROP was requested. RESULTS: Response rate was
      100.0% (44/44). All ROPs (100.0%) reported conducting some PR and rated its
      importance as 7/10 or higher (10 = extremely important). One-half of ROPs (52.3%)
      peer-reviewed >80% of curative treatment plans. ROPs reported performing PR
      "always/almost always" pretreatment (38.6%) or before 25% of radiation therapy
      delivery (52.3%). The majority of ROPs reported recommending major plan changes
      in <5% of plans (88.6%) and documenting findings in the medical record (58.1%).
      Barriers to PR were radiation oncologist availability (34.1%) and time
      constraints (27.3%). Facilitators included development of PR standards (97.7%)
      and education/support (90.9%). CONCLUSIONS: The ROPs perceive PR as highly
      important, but substantial variation in the extent, timing, and documentation of
      PR exists. The understanding of current PR activities, barriers, and facilitators
      will inform the development of initiatives to optimize PR in radiation oncology.

PMID- 27025161
TI  - Risk of radiation pneumonitis in patients receiving taxane-based trimodality
      therapy for locally advanced esophageal cancer.
AB  - PURPOSE: There are limited data regarding clinical and treatment factors
      associated with radiation pneumonitis (RP) in patients receiving taxane-based
      trimodality therapy for esophageal cancer. The purpose of this study was to
      identify predictors of RP in patients undergoing trimodality therapy. METHODS AND
      MATERIALS: We retrospectively reviewed patients undergoing chemoradiation
      followed by esophagectomy between 2006 and 2011. The association between clinical
      and dosimetric factors with RP was assessed using chi2 test and Mann-Whitney U
      test. Multivariable regression was used to assess the relationship between grade
      2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to
      identify threshold doses for RP. RESULTS: A total of 139 patients were included;
      19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic
      tumors (P = .038) and receiving higher radiation doses (P = .038) were more
      likely to develop grade 2+ RP. There was no association between taxane-based
      therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy
      (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was
      associated with an increased risk of grade 2+ RP. On multivariable regression,
      the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20
      (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated
      with grade 2+ RP. A V5 <=65% and V20 <=25% were identified as optimal thresholds
      for increased grade 2+ RP. CONCLUSIONS: Dosimetric parameters are strong
      predictors of symptomatic RP in patients undergoing trimodality therapy for
      esophageal cancer. Mitigating the risk of RP in these patients should be an
      important consideration during treatment planning.

PMID- 27025164
TI  - A prospective evaluation of open face masks for head and neck radiation therapy.
AB  - PURPOSE: Head and neck (HN) radiation therapy patients are typically immobilized
      with closed thermoplastic masks that cover the face and may cause discomfort. In
      this work, we examine the use of open masks for HN radiation therapy. METHODS AND
      MATERIALS: Fifty HN patients were prospectively randomized into 2 groups (25
      closed masks, 25 open masks). The open-mask group was monitored with surface
      imaging to evaluate intrafraction motion. Both groups underwent daily volumetric
      imaging. All daily images were rigidly registered to their respective planning
      images to evaluate spinal canal and mandible position as a check for
      interfraction posture change. Posture changes were determined by the amount the
      spinal canal and mandible contours from the planning images had to be expanded to
      cover the structures on each daily image set. The vector length (VL) of the
      intrafraction linear translations, spine, and mandible positions for each open
      mask patient were checked for correlation with fraction number using the Pearson
      r value. All patients were given a weekly survey ranking anxiety and
      claustrophobia from 0 to 10 (0 = no issue, 10 = extreme issue). RESULTS: The mean
      VL for all open-mask patients was 0.9 +/- 0.5 mm (1 standard deviation). Only 1
      patient showed significant correlation between VL and fraction number. The mean
      contour expansions to cover the spine and mandible were 1.5 +/- 0.9 mm and 1.8 +/
      1.3 mm for the closed-mask group, and 1.6 +/- 0.8 mm and 1.8 +/- 1.1 mm for the
      open-mask group. Both groups showed similar behavior relative to fraction number.
      The mean anxiety and claustrophobia scores were 1.63 and 1.44 for the closed-mask
      group, and 0.81 and 0.63 for the open-mask group. The groups were not
      significantly different. CONCLUSIONS: Open masks provide comparable
      immobilization and posture preservation to closed masks for HN radiation therapy.

PMID- 27025165
TI  - Can surface imaging improve the patient setup for proton postmastectomy chest
      wall irradiation?
AB  - PURPOSES/OBJECTIVES: For postmastectomy radiation therapy by proton beams, the
      usual bony landmark based radiograph setup technique is indirect because the
      target volumes are generally superficial and far away from major bony structures.
      The surface imaging setup technique of matching chest wall surface directly to
      treatment planning computed tomography was evaluated and compared to the
      traditional radiograph-based technique. METHODS AND MATERIALS: Fifteen
      postmastectomy radiation therapy patients were included, with the first 5
      patients positioned by standard radiograph-based technique; radiopaque makers,
      however, were added on the patient's skin surface to improve the relevance of the
      setup. AlignRT was used to capture patient surface images at different time
      points along the process, with the calculated position corrections recorded but
      not applied. For the remaining 10 patients, the orthogonal x-ray imaging was
      replaced by the AlignRT setup procedure followed by a beamline radiograph at the
      treatment gantry angle only as confirmation. The position corrections recorded
      during all fractions for all patients (28-31 each) were analyzed to evaluate the
      setup accuracy. The time spent on patient setup and treatment delivery was also
      analyzed. RESULTS: The average position discrepancy over the treatment course
      relative to the planning computed tomography was significantly larger in the
      radiograph only group, particularly in translations (3.2 +/- 2.0 mm in vertical,
      3.1 +/- 3.0 mm in longitudinal, 2.6 +/- 2.5 mm in lateral), than AlignRT assisted
      group (1.3 +/- 1.3 mm in vertical, 0.8 +/- 1.2 mm in longitudinal, 1.5 +/- 1.4 mm
      in lateral). The latter was well within the robustness limits (+/-3 mm) of the
      pencil beam scanning treatment established in our previous studies. The setup
      time decreased from an average of 11 minutes using orthogonal x-rays to an
      average of 6 minutes using AlignRT surface imaging. CONCLUSIONS: The use of
      surface imaging allows postmastectomy chest wall patients to be positioned more
      accurately and substantially more efficiently than radiograph only-based
      techniques.

PMID- 27025167
TI  - Active colloids at fluid interfaces.
AB  - If an active Janus particle is trapped at the interface between a liquid and a
      fluid, its self-propelled motion along the interface is affected by a net torque
      on the particle due to the viscosity contrast between the two adjacent fluid
      phases. For a simple model of an active, spherical Janus colloid we analyze the
      conditions under which translation occurs along the interface and we provide
      estimates of the corresponding persistence length. We show that under certain
      conditions the persistence length of such a particle is significantly larger than
      the corresponding one in the bulk liquid, which is in line with the trends
      observed in recent experimental studies.

PMID- 27025166
TI  - Robustness quantification methods comparison in volumetric modulated arc therapy
      to treat head and neck cancer.
AB  - BACKGROUND: To compare plan robustness of volumetric modulated arc therapy (VMAT)
      with intensity modulated radiation therapy (IMRT) and to compare the
      effectiveness of 3 plan robustness quantification methods. METHODS AND MATERIALS:
      The VMAT and IMRT plans were created for 9 head and neck cancer patients. For
      each plan, 6 new perturbed dose distributions were computed using +/-3 mm setup
      deviations along each of the 3 orientations. Worst-case analysis (WCA), dose
      volume histogram (DVH) band (DVHB), and root-mean-square dose-volume histogram
      (RVH) were used to quantify plan robustness. In WCA, a shaded area in the DVH
      plot bounded by the DVHs from the lowest and highest dose per voxel was
      displayed. In DVHB, we displayed the envelope of all DVHs in band graphs of all
      the 7 dose distributions. The RVH represents the relative volume on the vertical
      axis and the root-mean-square-dose on the horizontal axis. The width from the
      first 2 methods at different target DVH indices (such as D95% and D5%) and the
      area under the RVH curve for the target were used to indicate plan robustness.
      Results were compared using Wilcoxon signed-rank test. RESULTS: The DVHB showed
      that the width at D95% of IMRT was larger than that of VMAT (unit Gy) (1.59 vs
      1.18) and the width at D5% of IMRT was comparable to that of VMAT (0.59 vs 0.54).
      The WCA showed similar results between IMRT and VMAT plans (D95%: 3.28 vs 3.00;
      D5%: 1.68 vs 1.95). The RVH showed the area under the RVH curve of IMRT was
      comparable to that of VMAT (1.13 vs 1.15). No statistical significance was found
      in plan robustness between IMRT and VMAT. CONCLUSIONS: The VMAT is comparable to
      IMRT in terms of plan robustness. For the 3 quantification methods, WCA and DVHB
      are DVH parameter-dependent, whereas RVH captures the overall effect of
      uncertainties.

PMID- 27025168
TI  - Balanced motor primitive can explain generalization of motor learning effects
      between unimanual and bimanual movements.
AB  - Motor learning in unimanual and bimanual planar reaching movements has been
      intensively investigated. Although distinct theoretical frameworks have been
      proposed for each of these reaching movements, the relationship between these
      movements remains unclear. In particular, the generalization of motor learning
      effects (transfer of learning effects) between unimanual and bimanual movements
      has yet to be successfully explained. Here, by extending a motor primitive
      framework, we analytically proved that the motor primitive framework can
      reproduce the generalization of learning effects between unimanual and bimanual
      movements if the mean activity of each primitive for unimanual movements is
      balanced to the mean for bimanual movements. In this balanced condition, the
      activity of each primitive is consistent with previously reported neuronal
      activity. The unimanual-bimanual balance leads to the testable prediction that
      generalization between unimanual and bimanual movements is more widespread to
      different reaching directions than generalization within respective movements.
      Furthermore, the balanced motor primitive can reproduce another previously
      reported phenomenon: the learning of different force fields for unimanual and
      bimanual movements. 

PMID- 27025170
TI  - Macroscopic alignment of chromonic liquid crystals using patterned substrates.
AB  - We demonstrate an efficient technique to align lyotropic chromonic liquid
      crystals (LCLCs) using secondary sputtering lithography (SSL). Monodomains of
      LCLCs prepared using SSL maintained their stable alignment for days. A
      generalization of Berreman's theory was employed to determine the anchoring
      strength of LCLCs on tessellated surface patterns. The anchoring energy initially
      increases with the amplitude (A) of the grooves and excellent alignment of LCLCs
      was observed when the amplitude of the grooves is equal to half its wavelength
      (lambda). We also note that the anchoring energy levels off above qA~ 3 (where q
      = 2pi/lambda), which suggests that increasing qA beyond a certain value does not
      provide any further advantage for the alignment of LCLCs. This finding provides a
      useful optimization criterion for the fabrication of the patterned cells to
      achieve stable monodomain alignment of LCLCs. Our analysis also explains why good
      alignment of LCLCs has been a difficult task.

PMID- 27025169
TI  - Conservation priorities of Iberoamerican pig breeds and their ancestors based on
      microsatellite information.
AB  - Criollo pig breeds are descendants from pigs brought to the American continent
      starting with Columbus second trip in 1493. Pigs currently play a key role in
      social economy and community cultural identity in Latin America. The aim of this
      study was to establish conservation priorities among a comprehensive group of
      Criollo pig breeds based on a set of 24 microsatellite markers and using
      different criteria. Spain and Portugal pig breeds, wild boar populations of
      different European geographic origins and commercial pig breeds were included in
      the analysis as potential genetic influences in the development of Criollo pig
      breeds. Different methods, differing in the weight given to within- and between
      breed genetic variability, were used in order to estimate the contribution of
      each breed to global genetic diversity. As expected, the partial contribution to
      total heterozygosity gave high priority to Criollo pig breeds, whereas Weitzman
      procedures prioritized Iberian Peninsula breeds. With the combined within- and
      between-breed approaches, different conservation priorities were achieved. The
      Core Set methodologies highly prioritized Criollo pig breeds (Cr. Boliviano, Cr.
      Pacifico, Cr. Cubano and Cr. Guadalupe). However, weighing the between- and
      within-breed components with FST and 1-FST, respectively, resulted in higher
      contributions of Iberian breeds. In spite of the different conservation
      priorities according to the methodology used, other factors in addition to
      genetic information also need to be considered in conservation programmes, such
      as the economic, cultural or historical value of the breeds involved.

PMID- 27025171
TI  - The health crisis of mental health stigma.

PMID- 27025172
TI  - Domestic violence in China.

PMID- 27025173
TI  - Campaigning for kidney health.

PMID- 27025174
TI  - ICON-6: the danger of changing study design midstream.

PMID- 27025176
TI  - Syria's health crisis: 5 years on.

PMID- 27025177
TI  - Experts sceptical about Nigeria's free health-care plans.

PMID- 27025178
TI  - Fukushima disaster: road to recovery remains long.

PMID- 27025179
TI  - Judith Bradford: a pioneer of research on LGBT health.

PMID- 27025180
TI  - Time to recognise countries' preferences in HIV control.

PMID- 27025181
TI  - Mindfulness-based cognitive therapy for depression.

PMID- 27025182
TI  - Changing oral vaccine to inactivated polio vaccine might increase mortality.

PMID- 27025183
TI  - Hepatology training in the UK.

PMID- 27025184
TI  - Department of Error.

PMID- 27025185
TI  - Department of Error.

PMID- 27025186
TI  - Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a
      randomised, double-blind, placebo-controlled phase 3 trial.
AB  - BACKGROUND: Angiogenesis is a validated clinical target in advanced epithelial
      ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth
      factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent
      ovarian cancer. We assessed efficacy and safety of cediranib in combination with
      platinum-based chemotherapy and as continued maintenance treatment in patients
      with first relapse of platinum-sensitive ovarian cancer. METHODS: In this
      randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we
      randomly assigned patients aged 18 years or older with relapsed platinum
      sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain,
      and the UK. Participants received up to six cycles of platinum-based chemotherapy
      (once every 3 weeks) then entered a maintenance phase. Participants were randomly
      allocated (2:3:3), with five stratification factors and in alternating blocks, to
      receive placebo alongside chemotherapy and then placebo only maintenance (arm A;
      reference), cediranib 20 mg once-daily alongside chemotherapy then placebo only
      maintenance (arm B; concurrent), or cediranib 20 mg once-daily alongside
      chemotherapy then cediranib 20 mg once-daily maintenance (arm C; maintenance).
      Patients continued treatment to progression or excessive toxic effects. The
      primary efficacy endpoint was progression-free survival between arms A and C.
      Efficacy analysis was by intention to treat. Safety was assessed in all patients
      who received the allocated study drug. This trial is registered with
      ClinicalTrials.gov, number NCT00532194; the ISRCTN registry, number
      ISRCTN68510403; and ANZ Clinical Trials Registry, number ACTRN1261000016003.
      FINDINGS: We randomly assigned 486 [corrected] women between Nov 13, 2007, and
      Dec 23, 2011; results presented are for 456 patients randomly assigned subsequent
      to the 30mg safety phase. During a median of 19.5 months (IQR 14-26) follow-up,
      113 (96%) of 118 women assigned to arm A and 141 (86%) of 164 assigned to arm C
      had disease progression. Median progression-free survival was 11.0 months (95% CI
      10.4-11.7) in arm C and 8.7 months (7.7-9.4) in arm A (hazard ratio 0.56, 0.44
      0.72, p<0.0001). 156 (90%) of 174 patients in arm B had disease progression, and
      median progression-free survival was 9.9 months (95% CI 9.4-10.5). Diarrhoea,
      neutropenia, hypertension, and voice changes were significantly more common,
      during chemotherapy with cediranib, and diarrhoea, hypothyroidism and voice
      changes were more common during maintenance. Poor compliance with cediranib was
      noted during maintenance treatment with toxic effects being the most common cause
      for discontinuation. INTERPRETATION: Cediranib, when given orally with
      chemotherapy and continued as maintenance, yielded a meaningful improvement
      [corrected] in progression-free survival in women with recurrent platinum
      sensitive ovarian cancer, albeit with added toxic effects. The positive results
      in ICON6 could provide women with a new therapeutic option for recurrent ovarian
      cancer. Assessment of the secondary endpoint of overall survival will need longer
      follow-up. FUNDING: Medical Research Council, Cancer Research UK, Canadian Cancer
      Society Research Institute, Cancer Australia, National Gynecological Cancer
      Centre, and AstraZeneca.

PMID- 27025187
TI  - Prognostication Value of Descending Corticospinal Tract DWI Signal in Neonatal
      Cerebral Sinovenous Thrombosis.
AB  - BACKGROUND: Descending corticospinal tract diffusion-weighted magnetic resonance
      imaging (MRI) signal is predictive of poor motor outcome in neonatal and
      childhood arterial ischemic stroke. However, descending corticospinal tract
      diffusion-weighted MRI signal has not been documented in the setting of cerebral
      sinovenous thrombosis, and its role is not understood. OBJECTIVE: We describe a
      neonate with cerebral sinovenous thrombosis, extensive diffusion restriction, and
      bilateral descending corticospinal tract diffusion-weighted MRI signal on MRI of
      the brain. We discuss the underlying mechanisms and implications of these
      findings in venous ischemia. CONCLUSION: The prognostic value of descending
      corticospinal tract diffusion-weighted MRI signal differs when observed in
      cerebral sinovenous thrombosis from when observed in arterial ischemic stroke.
      Consequently, caution should be exercised in using descending corticospinal tract
      diffusion-weighted MRI signal to predict outcome in children with cerebral
      sinovenous thrombosis.

PMID- 27025188
TI  - Neonatal Magnesium Levels Between 24 and 48 Hours of Life and Outcomes for
      Epilepsy and Motor Impairment in Premature Infants.
AB  - OBJECTIVE: Elevated rates of epilepsy and motor impairments including cerebral
      palsy are observed in children who were born prematurely. Maternal antenatal
      magnesium supplementation has been associated with decreased rates of cerebral
      palsy in infants born prematurely. Our objective was to determine whether the
      neonatal serum magnesium level between 24 and 48 hours after birth is associated
      with better long-term neurodevelopmental outcomes (epilepsy, motor impairment) in
      premature infants. METHODS: We performed a retrospective cohort analysis in
      infants born less than 37-weeks gestation over a ten-year period. Prenatal,
      perinatal, and postnatal clinical and demographic information was collected.
      Crude and adjusted odds ratios were estimated under generalized linear models
      with generalized estimating equations to examine the association of the neonatal
      serum magnesium level between 24 and 48 hours after birth with the risk of
      epilepsy and/or motor impairment (spasticity; hypotonia; cerebral palsy).
      RESULTS: The final cohort included 5461 infants born less than 37-weeks gestation
      from 2002 to 2011. The adjusted relative risk ratio for the combined outcomes of
      epilepsy and/or motor impairment, controlling for gestational age, current age,
      maternal magnesium supplementation, maternal steroid administration, five-minute
      Apgar score, neonatal infection, need for vasopressor use, and birth weight and
      with serum magnesium level as the main independent variable, was 0.85 (P = 0.24).
      Stratified analyses by gestational age less than 32 or greater than 32 weeks were
      not significantly associated with adverse neurodevelopmental outcome (risk ratio
      = 0.79 and 1.2, P = 0.12 and 0.49, respectively). A multivariate analysis for the
      risk of motor impairment alone had a risk ratio of 0.94 (P = 0.72). CONCLUSION:
      This study demostrates that the neonatal magnesium level between 24 and 48 hours
      of life in premature infants is not significantly associated with the risk for
      developing epilepsy or motor impairment.

PMID- 27025189
TI  - Characterization and compression of dissipative-soliton-resonance pulses in fiber
      lasers.
AB  - We report numerical and experimental studies of dissipative-soliton-resonance
      (DSR) in a fiber laser with a nonlinear optical loop mirror. The DSR pulse
      presents temporally a flat-top profile and a clamped peak power. Its spectrum has
      a rectangle profile with characteristic steep edges. It shows a unique behavior
      as pulse energy increases: The rectangle part of the spectrum is unchanged while
      the newly emerging spectrum sits on the center part and forms a peak.
      Experimental observations match well with the numerical results. Moreover, the
      detailed evolution of the DSR pulse compression is both numerically and
      experimentally demonstrated for the first time. An experimentally obtained DSR
      pulse of 63 ps duration is compressed down to 760 fs, with low-intensity
      pedestals using a grating pair. Before being compressed to its narrowest width,
      the pulse firstly evolves into a cat-ear profile, and the corresponding
      autocorrelation trace shows a crown shape, which distinguishes itself from
      properties of other solitons formed in fiber lasers. 

PMID- 27025190
TI  - Transgenerational programming of longevity and reproduction by post-eclosion
      dietary manipulation in Drosophila.
AB  - Accumulating evidence suggests that early-life diet may program one's health
      status by causing permanent alternations in specific organs, tissues, or
      metabolic or homeostatic pathways, and such programming effects may propagate
      across generations through heritable epigenetic modifications. However, it
      remains uninvestigated whether postnatal dietary changes may program longevity
      across generations. To address this question of important biological and public
      health implications, newly-born flies (F0) were collected and subjected to
      various post-eclosion dietary manipulations (PDMs) with different protein
      carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein)
      contents or a control diet (CD). Longevity and fecundity analyses were performed
      with these treated F0 flies and their F1, F2 and F3 offspring, while maintained
      on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM
      extended longevity significantly up to the F3 generation. Furthermore, the LP
      reduced while the IP PDM increased lifetime fecundity across the F0-F2
      generations. Our observations establish the first animal model for studying
      transgenerational inheritance of nutritional programming of longevity, making it
      possible to investigate the underlying epigenetic mechanisms and identify gene
      targets for drug discovery in future studies.

PMID- 27025191
TI  - Metagenome changes in the biogas producing community during anaerobic digestion
      of rice straw.
AB  - The present investigation was undertaken to study the microbial community
      succession in a sour and healthy digester. Ion torrent next-generation sequencing
      (NGS)-based metagenomic approach indicated abundance of hydrolytic bacteria and
      exclusion of methanogens and syntrophic bacteria in sour digester. Functional
      gene analysis revealed higher abundance of enzymes involved in acidogenesis and
      lower abundance of enzymes associated with methanogenesis like Methyl coenzyme M
      reductase, F420 dependent reductase and Formylmethanofuran dehydrogenase in sour
      digester. Increased abundance of methanogens (Methanomicrobia) and genes involved
      in methanogenesis was observed in the restored/healthy digester highlighting
      revival of pH sensitive methanogenic community. 

PMID- 27025192
TI  - Satellite-derived mineral mapping and monitoring of weathering, deposition and
      erosion.
AB  - The Earth's surface comprises minerals diagnostic of weathering, deposition and
      erosion. The first continental-scale mineral maps generated from an imaging
      satellite with spectral bands designed to measure clays, quartz and other
      minerals were released in 2012 for Australia. Here we show how these satellite
      mineral maps improve our understanding of weathering, erosional and depositional
      processes in the context of changing weather, climate and tectonics. The clay
      composition map shows how kaolinite has developed over tectonically stable
      continental crust in response to deep weathering during northwardly migrating
      tropical conditions from 45 to 10 Ma. The same clay composition map, in
      combination with one sensitive to water content, enables the discrimination of
      illite from montmorillonite clays that typically develop in large depositional
      environments over thin (sinking) continental crust such as the Lake Eyre Basin.
      Cutting across these clay patterns are sandy deserts that developed <10 Ma and
      are well mapped using another satellite product sensitive to the particle size of
      silicate minerals. This product can also be used to measure temporal gains/losses
      of surface clay caused by periodic wind erosion (dust) and rainfall inundation
      (flood) events. The accuracy and information content of these satellite mineral
      maps are validated using published data.

PMID- 27025193
TI  - Sulforaphane ameliorates the insulin responsiveness and the lipid profile but
      does not alter the antioxidant response in diabetic rats.
AB  - Diabetes is one of the most prevalent chronic non-communicable diseases and is
      characterized by hyperglycemia and increased oxidative stress. These two
      alterations are also responsible for the main diabetic complications:
      cardiovascular disease, retinopathy, nephropathy and peripheral neuropathy.
      Diabetes progression is governed by pancreatic beta-cell failure, and recent
      studies showed that sulforaphane (SFN) might be able to prevent this change,
      preserving insulin production. Consequently, our goal was to test the effects of
      SFN on metabolic parameters related to diabetic complications and antioxidant
      defenses (superoxide dismutase, catalase and sulfhydryl groups) in the pancreas,
      liver and kidney of non-diabetic and diabetic rats. Male Wistar rats were treated
      with water or 0.5 mg kg(-1) SFN i.p. for 21 days after diabetes induction. In
      diabetic animals treated with SFN, the serum levels of total cholesterol, non-HDL
      cholesterol and triacylglycerols were similar to those of non-diabetic animals,
      and the insulin responsiveness was higher than that of the diabetic animals that
      did not receive the compound. No effect of SFN on the superoxide dismutase and
      catalase activity or sulfhydryl groups was observed in the pancreas, liver or
      kidney of the treated animals. We conclude that SFN ameliorates some features of
      clinical diabetic complications particularly the lipid profile and insulin
      responsiveness, but it does not modulate the antioxidant response induced by
      superoxide dismutase, catalase and sulfhydryl groups in the evaluated organs. 

PMID- 27025195
TI  - Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity.
AB  - OBJECTIVES: Chronic consumption of high-fructose corn syrup (HFCS) causes several
      problems such as insulin resistance. The goal of the study was to investigate
      pancreatic damage induced by chronic HFCS consumption and the protective effects
      of alpha lipoic acid (ALA) on pancreatic cells. METHODS: Wistar Albino, 4-month
      old, female rats weighing 250-300 g were randomly distributed into three groups,
      each containing eight rats. The study included an HFCS group, an HFCS + ALA
      administered group and a control group (CON). The prepared 30% solution of HFCS
      (F30) (24% fructose, 28% dextrose) was added to the drinking water for 10 weeks.
      ALA treatment was begun 4 weeks after the first HFCS administration (100
      mg/kg/oral, last 6 weeks). Rats were anaesthetised and euthanised by cervical
      dislocation 24 h after the last ALA administration. Blood samples for biochemical
      tests (amylase, lipase, malondialdehyde (MDA) and catalase (CAT)) and tissue
      samples for histopathological and immunohistochemical examinations (caspase-3,
      insulin and glucagon) were collected. RESULTS: Comparing the control and HFCS
      groups, serum glucose (150.92 +/- 39.77 and 236.50 +/- 18.28, respectively, p <
      0.05), amylase (2165.00 +/- 150.76 and 3027.66 +/- 729.19, respectively, p <
      0.01), lipase (5.58 +/- 2.22 and 11.51 +/- 2.74, respectively, p < 0.01) and
      pancreatic tissue MDA (0.0167 +/- 0.004 and 0.0193 +/- 0.006, respectively, p <
      0.05) levels were increased, whereas tissue CAT (0.0924 +/- 0.029 and 0.0359 +/-
      0.023, respectively, p < 0.05) activity decreased in the HFCS group
      significantly. Histopathological examination revealed degenerative and necrotic
      changes in Langerhans islet cells and slight inflammatory cell infiltration in
      pancreatic tissue in the HFCS group. Immunohistochemically there was a
      significant decrease in insulin (2.85 +/- 0.37 and 0.87 +/- 0.64, respectively, p
      < 0.001) and glucagon (2.71 +/- 0.48 and 1.00 +/- 0.75, respectively, p < 0.001)
      secreting cell scores, whereas a greater increase in caspase-3 (0.14 +/- 0.37 and
      1.00 +/- 0.75, respectively, p < 0.05) expression was seen in this group compared
      with the controls. In the ALA-treated group, all of these pathologic conditions
      were improved. CONCLUSIONS: This study indicated HFCS induced pancreatic lesions,
      but ALA had ameliorative effects.

PMID- 27025194
TI  - Inherited thrombocytopenia: novel insights into megakaryocyte maturation,
      proplatelet formation and platelet lifespan.
AB  - The study of patients with inherited bleeding problems is a powerful approach in
      determining the function and regulation of important proteins in human platelets
      and their precursor, the megakaryocyte. The normal range of platelet counts in
      the bloodstream ranges from 150 000 to 400 000 platelets per microliter and is
      normally maintained within a narrow range for each individual. This requires a
      constant balance between thrombopoiesis, which is primarily controlled by the
      cytokine thrombopoietin (TPO), and platelet senescence and consumption.
      Thrombocytopenia can be defined as a platelet count of less than 150 000 per
      microliter and can be acquired or inherited. Heritable forms of thrombocytopenia
      are caused by mutations in genes involved in megakaryocyte differentiation,
      platelet production and platelet removal. In this review, we will discuss the
      main causative genes known for inherited thrombocytopenia and highlight their
      diverse functions and whether these give clues on the processes of platelet
      production, platelet function and platelet lifespan. Additionally, we will
      highlight the recent advances in novel genes identified for inherited
      thrombocytopenia and their suggested function. 

PMID- 27025196
TI  - Investigation of the early stages of human gammaD-crystallin aggregation process.
AB  - Cataract, a major cause of visual impairment worldwide, is a common disease of
      the eye lens related to protein aggregation. Several factors including the
      exposure of ultraviolet irradiation and possibly acidic condition may induce the
      unfolding and subsequent aggregation of the crystallin proteins leading to
      crystalline lens opacification. Human gammaD-crystallin (HgammaDC), a 173 residue
      monomeric protein, abundant in the nucleus of the human eye lens, has been shown
      to aggregate and form amyloid fibrils under acidic conditions and that this
      aggregation route is thought to be a potential initiation pathway for the onset
      of age-related nuclear cataract. However, the underlying mechanism of fibril
      formation remains elusive. This report is aimed at examining the structural
      changes and possible amyloid fibril formation pathway of HgammaDC using molecular
      dynamics and molecular docking simulations. Our findings demonstrated that
      incubation of HgammaDC under the acidic condition redistributes the protein
      surface charges and affects the protein interaction with its surrounding solvent
      environment. This brings about a twist motion in the overall tertiary structure
      that gives rise to newly formed anti-parallel beta-strands in the C-terminal
      flexible loop regions. The change in protein structural conformation also
      involves an alteration in specific salt-bridge interactions. Altogether, these
      findings revealed a plausible mechanism for amyloid fibril formation of HgammaDC
      that is important to the early stages of HgammaDC aggregation involved in
      cataractogenesis.

PMID- 27025197
TI  - Narrowing the Skills Gap for Innovation: An Empirical Study in the Hospital
      Sector.
AB  - BACKGROUND: The current financial crisis and the increasing burden of chronic
      diseases are challenging hospitals to enhance their innovation capacity to
      deliver new and more effective health services. However, the shortage of skills
      has been widely recognized as a key obstacle for innovation. Ensuring the
      presence of a skilled workforce has become a priority for the health system in
      Portugal and across Europe. OBJECTIVE: The aim of this study was to examine the
      demand of new skills and their influence in both investments in innovation and
      development of skills. METHODS: We used a mixed-methods approach combining
      statistical analysis of data survey and content analysis of semistructured
      interviews with the Administration Boards of hospitals, using a nominal group
      technique. RESULTS: The results illustrate an increasing demand of a broad range
      of skills for innovation development, including responsibility and quality
      consciousness (with a significant increase of 55%, 52/95), adaptation skills
      (with an increase of 44%, 42/95) and cooperation and communication skills (with
      an increase of 55%, 52/95). Investments in the development of skills for
      innovation are mainly focused on aligning professional training with an
      organizational strategy (69%, 66/95) as well as collaboration in taskforces (61%,
      58/95) and cross-department teams (60%, 57/95). However, the dynamics between the
      supply and demand of skills for innovation are better explained through a broader
      perspective of organizational changes towards enhancing learning opportunities
      and engagement of health professionals to boost innovation. CONCLUSIONS: The
      results of this study illustrate that hospitals are unlikely to enhance their
      innovation capacity if they pursue strategies failing to match the skills needed.
      Within this context, hospitals with high investments in innovation tend to invest
      more in skills development. The demand of skills and investments in training are
      influenced by many other factors, including the hospital's strategies, as well as
      changes in the work organization. Relevant implications for managers and policy
      makers can be drawn from the empirical findings of this paper, building on the
      current efforts from leading innovating hospitals that are already defining the
      future of health care.

PMID- 27025198
TI  - CHA2DS2-VASc-HS score in non-ST elevation acute coronary syndrome patients:
      assessment of coronary artery disease severity and complexity and comparison to
      other scoring systems in the prediction of in-hospital major adverse
      cardiovascular events.
AB  - OBJECTIVE: We recently described the CHA2DS2-VASc-HS score as a novel predictor
      of coronary artery disease (CAD) severity in stable CAD patients. We aimed to
      assess the accuracy of the CHA2DS2-VASc-HS score in the determination of CAD
      severity and complexity and its availability in the risk stratification of in
      hospital major adverse cardiovascular events (MACE) in non-ST elevation acute
      coronary syndrome (NSTE-ACS) patients. METHODS: We prospectively analyzed the
      clinical and angiographic data of consecutive NSTE-ACS patients in our clinic.
      Patients were classified into three tertiles according to their SYNTAX score
      (SS): tertile 1 had an SS of 0-22; tertile 2 had an SS of 23-32; and tertile 3
      had an SS of >32. There were no specific exclusion criteria except for previous
      coronary artery bypass grafting (CABG) because SS was validated for only native
      coronary arteries for this study. We used the following analyses: chi2 or
      Fisher's exact tests, one-way analysis of variance or Kruskal-Wallis tests,
      Pearson's or Spearman's tests, the receiver operating characteristics (ROC) curve
      analysis, the area under the curve (AUC) or C-statistic, and pairwise comparisons
      of the ROC curves. RESULTS: A total of 252 patients were enrolled. There were 131
      patients in tertile 1, 79 in tertile 2, and 42 in tertile 3. The number of
      diseased vessels was correlated with the Global Registry for Acute Coronary
      Events (GRACE) (p<0.001), Thrombolysis in Myocardial Infarction (TIMI) (p<0.001),
      and CHA2DS2-VASc-HS (p<0.001) scores. In the ROC curve analyses, the cut-off
      value of the CHA2DS2-VASc-HS score in the prediction of in-hospital MACE was >5
      with a sensitivity of 69.6% and specificity of 90.3% (AUC: 0.804, 95%: CI 0.750
      0.851, p<0.001). We also compared the diagnostic accuracy of the CHA2DS2-VASc-HS
      score with the TIMI and GRACE risk scores in the determination of the in-hospital
      MACE and found no differences. CONCLUSION: The CHA2DS2-VASc-HS score was
      positively correlated with the severity and complexity of CAD. We also found that
      CHA2DS2-VASc-HS was comparable with other risk scores for the risk stratification
      of the in-hospital MACE of NSTE-ACS patients. Therefore, it may play an important
      role as a predictive model of NSTE-ACS patients in clinical practice.

PMID- 27025199
TI  - Cardiac autonomic nervous dysfunction detected by both heart rate variability and
      heart rate turbulence in prediabetic patients with isolated impaired fasting
      glucose.
AB  - OBJECTIVE: Cardiac autonomic nervous dysfunction (CAND), a severe complication of
      diabetes, has also been shown to affect prediabetic patients. The role of
      isolated impaired fasting plasma glucose (IFG), a subtype of prediabetes, is not
      clear in the pathogenesis of CAND. The aim of this study was to examine the
      relationship between isolated IFG and cardiac autonomic function using heart rate
      variability (HRV) and heart rate turbulence (HRT) indices derived from 24-h
      Holter electrocardiogram recordings. METHODS: This observational, prospective,
      cross-sectional study examined 400 consecutive subjects divided into three groups
      according to oral glucose tolerance test results: the control group [Group I,
      fasting plasma glucose (FPG) <100 mg/dL and normal glucose tolerance, n=193], the
      isolated IFG group (Group II, FPG >=100 and <126 mg/dL, n=134), and the isolated
      impaired glucose tolerance (IGT), both IFG and IGT, or newly diagnosed diabetes'
      group (Group III, n=73). Patients with non-sinus rhythm, known diabetes mellitus,
      coronary artery disease, heart failure, severe valvular disease, or receiving
      medical therapy that may affect HRV and HRT indices were excluded. Time domain
      HRV parameters, turbulence onset (TO), turbulence slope (TS), and HRT category
      were examined. Chi-square, one-way analysis of variance, Kruskal-Wallis H, and
      Mann-Whitney U tests were used to compare variables where appropriate. The
      correlation between Holter data and FPG levels was analyzed using the Spearman's
      test. Multiple linear regression analysis was performed to identify independent
      predictors of the HRV and HRT parameters. RESULTS: Median (interquartile range 25
      75) FPG levels in Groups I, II, and III were 89 (83/93) mg/dL, 109 (104/116)
      mg/dL, and 174 (150.5/197) mg/dL, respectively. There were significant
      differences in HRV and HRT parameters between and among all groups. While HRV
      parameters and TS decreased from Group I to Group III, TO and HRT category
      gradually increased. Additionally, FPG level was significantly correlated with
      SDNN, r=-0.220; SDNN index, r=-0.192; SDANN, r=-0.207; RMSSD, r=-0.228; pNN50, r=
      0.226; TO, r=0.354; and TS, r=-0.331 (all p<0.001). CONCLUSION: CAND, as detected
      by both HRV and HRT, appear to be present in the isolated IFG subtype of
      prediabetes.

PMID- 27025200
TI  - beta-2 microglobulin level is negatively associated with global left ventricular
      longitudinal peak systolic strain and left atrial volume index in patients with
      chronic kidney disease not on dialysis.
AB  - OBJECTIVE: There are many factors related to high left atrial volume index (LAVI)
      and global left ventricular longitudinal peak systolic strain (GLS-%) decline in
      chronic kidney disease. The purpose of our study is to investigate the relation
      between the beta-2 microglobulin (beta-2u ) and GLS-% and LAVI in patients with
      chronic kidney disease not yet on dialysis. METHODS: Our study was a non
      randomized, controlled, prospective study. We included 87 consecutive patients
      with eGFR levels below 60 ml/min/m2 not on dialysis and 82 normal healthy
      individuals with complaints of atypical chest pain and negative stress tests as
      control group in our study. Patients with hospitalization related to dialysis or
      heart failure attacks within 3 months, active malignancy, malnutrition,
      pregnancy, and uncontrolled hypertension were excluded. Brachial pulse wave
      velocity (PWV), augmentation index, augmentation pressure and central
      hemodynamics, and PWV analysis were performed in order to assess the arterial
      stiffness and blood pressure. According to the distribution of data, Spearman and
      Pearson correlations and multiple linear regression were used to determine
      significant and independent factor associated with high LAVI and low GLS-%.
      RESULTS: There were significant correlations between beta-2u with LAVI (r=0.313,
      p=0.004) and with GLS-% (r=-0.222, p=0.04). In multiple linear regression, the
      relationship between beta-2u with GLS-% [beta=-0.037, 95% CI (-0.062, -0.013),
      p=0.004] and LAVI [beta=4.522, 95% CI (2.806, 6.238), p<0.001] was independent of
      age, PWV, central and peripheral blood pressures, parathormone, CalciumXPhospor,
      Hgb levels, and eGFR. CONCLUSION: Increasing beta-2u levels were found to be
      associated with increased LAVI and decreased GLS-%. Additional experimental
      studies are needed to clarify these relationships.

PMID- 27025201
TI  - Aortic flow propagation velocity, epicardial fat thickness, and osteoprotegerin
      level to predict subclinical atherosclerosis in patients with nonalcoholic fatty
      liver disease.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease is the most common cause of liver
      dysfunction in Western countries and an independent risk factor for
      atherosclerotic heart disease. Appropriate noninvasive parameters are lacking for
      optimal risk stratification of cardiovascular disease in these patients. We
      evaluated several recently discovered noninvasive parameters for atherosclerosis
      in patients with nonalcoholic fatty liver disease: epicardial fat thickness,
      aortic flow propagation velocity, and osteoprotegerin level. METHODS: Forty-one
      patients (27 men and 14 women; mean age, 37.9+/-8.9 years) with nonalcoholic
      fatty liver disease and 37 control subjects (17 men and 20 women; mean age,
      34.5+/-8.6 years) were enrolled in this observational case-control study.
      Patients with nonalcoholic fatty liver disease diagnosed at a gastroenterology
      outpatient clinic were included. Patients with cardiac pathology other than
      hypertension were excluded. Epicardial fat thickness and aortic flow propagation
      velocity were measured by echocardiography. The serum concentration of
      osteoprotegerin was measured using a commercial enzyme-linked immunosorbent assay
      kit. RESULTS: Nonalcoholic fatty liver disease patients exhibited a significantly
      lower aortic flow propagation velocity (155.17+/-30.00 vs. 179.00+/-18.14 cm/s,
      p=0.000) and significantly higher epicardial fat thickness (0.51+/-0.25 vs.
      0.29+/-0.09 cm, p=0.000) than control subjects. Osteoprotegerin levels were
      higher, but not significant, in patients with nonalcoholic fatty liver disease
      (28.0+/-13.0 vs. 25.2+/-10.8 pg/mL, p=0.244). Binary logistic regression analysis
      showed that aortic flow propagation velocity (OR, -0.973; 95% CI, 0.947-0.999)
      and waist circumference (OR, -1.191; 95% CI, 1.088-1.303) were independent
      predictors of nonalcoholic fatty liver disease. CONCLUSION: In this study,
      epicardial fat thickness and osteoprotegerin level were higher and aortic flow
      propagation velocity was lower in patients with nonalcoholic fatty liver disease.
      Early detection of abnormal epicardial fat thickness and aortic flow propagation
      velocity may warrant a search for undetected cardiovascular disease in patients
      with nonalcoholic fatty liver disease.

PMID- 27025202
TI  - Early and long-term outcomes and quality of life after concomitant mitral valve
      surgery, left atrial size reduction, and radiofrequency surgical ablation of
      atrial fibrillation.
AB  - OBJECTIVE: Atrial fibrillation (AF) is the most formidable supraventricular
      tachyarrhythmia, which worsens the natural course of mitral valve disease. In
      this study, we evaluated early and long-term results and quality of life (QOL)
      after simultaneous surgical radiofrequency ablation (RFA) of AF, left atrial
      reduction and mitral valve repair or replacement. METHODS: Overall, 147 patients
      with mitral valve diseases who underwent mitral valve surgery were included in
      this prospective cohort study. Patients were divided into two groups according to
      the type of operation: the study group-patients after mitral valve surgery with
      concomitant radiofrequency surgical ablation and left atrial reduction procedure
      (54 patients), and the control group-patients undergoing only mitral valve
      surgery (93 cases). We assessed AF recurrence and sinus rhythm restoration rates
      and mortality rates, QOL measures, postoperative complications rates, and left
      atrial size during follow-up. RESULTS: In the study group, sinus rhythm
      restoration rate in the early postoperative period was 63%, but at the time of
      discharge it reduced to 29%; after 6 months, it significantly increased to 72%
      and after 3 years, to 81% (p=0.02). In the control group, the sinus rhythm
      restored only in 14% after 1 year, and at 3 years, it was 22%, although in the
      early postoperative period it, was 43%. Analysis of left atrial size before and
      after surgery showed that dimension significantly reduced in both groups (study
      group, p=0.013; control group, p=0.024). In addition, in patients undergoing
      surgical RFA procedure, there was a significant association between shorter heart
      disease history (p=0.02) and shorter AF history (p=0.074) with maintenance of
      sinus rhythm. The mortality rate in the study group was 4% (two patients) and in
      the control group 5% (five patients). Comparison of QOL measures between study
      and control groups after 1 year showed that patients undergoing concomitant
      atrial reduction surgery and RFA had significant improvement of QOL physical
      (p=0.03) and role (p=0.03) functioning, heartbeat (p=0.01), general (p=0.03) and
      mental health (p=0.01), vitality (p=0.007), and social role (p=0.02) functioning
      measures as compared to preoperative state, being higher than in patients who
      underwent only mitral valve surgery. CONCLUSION: Application of surgical RFA
      using irrigated cooling electrode and atrial reduction during mitral valve
      surgery is associated with higher restoration and maintenance of SR as compared
      to patients undergoing only mitral valve surgery. We did not observe
      complications related to AF surgery that required permanent pacemaker
      implantation. Performing concomitant surgery as surgical RFA, atrial reduction
      along with mitral valve surgery, improves QOL in the short- and long-term and
      reduces the feeling of heartbeat and discomfort.

PMID- 27025203
TI  - Relationship between metabolic syndrome and epicardial fat tissue thickness in
      patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: An increase in epicardial fat tissue (EFT) thickness was found to be
      associated with metabolic syndrome (MS) and ischemic heart disease. MS is a
      comorbidity of chronic obstructive pulmonary disease (COPD) resulting from the
      accompanying systemic inflammation. The aim of our study was to investigate the
      usefulness of EFT thickness to predict MS in COPD patients. METHODS: COPD
      patients admitted to our clinic during January-December 2014 and healthy controls
      were included in this prospective case control study. Patients with
      comorbidities, COPD exacerbation, and malignancies were excluded. Patients and
      controls were compared in terms of anthropometric measurements, MS-related
      examination and laboratory findings, pulmonary function tests, and EFT thickness.
      The correlations between EFT thickness and markers of MS in COPD were evaluated
      using the Student's t-test and logistic regression analysis. RESULTS: COPD
      patients and controls were composed of 82 and 84 individuals, respectively. MS
      was diagnosed in 31 (37.8%) COPD patients. The EFT thickness was significantly
      higher in COPD patients than in the controls and was also higher in COPD patients
      with MS than in those without MS (all p<0.001). Each 1-mm increment of EFT raised
      the risk of MS two-fold (p=0.011, OR=2.08, 95% CI: 1.18-3.68). Increase in
      triglyceride level (p=0.004, OR=1.02, 95% CI: 1.01-1.03) and reduction in forced
      vital capacity (p=0.025, OR=0.26, 95% CI: 0.08-0.84) were found to be associated
      with increased MS risk. The cut-off value for EFT thickness in the prediction of
      MS in COPD patients was 6.75 mm (sensitivity: 83%, specificity: 65%). CONCLUSION:
      EFT thickness is a non-invasive and easily available parameter, which is valuable
      in the prediction of increased MS risk in COPD patients. Early diagnosis of
      patients at risk of MS may help to prevent ischemic heart disease in these
      patients.

PMID- 27025204
TI  - Interferon-gamma release assays in patients with Mycobacterium kansasii pulmonary
      infection: A retrospective survey.
AB  - OBJECTIVES: Interferon-gamma release assays (IGRAs) can be positive in patients
      infected with Mycobacterium kansasii (M. kansasii), which carries some of
      Mycobacterium tuberculosis specific antigens adopted for IGRAs. Our aim is to
      evaluate positive rate and factors associated with positive IGRAs in patients
      with M. kansasii pulmonary infection. METHODS: We retrospectively investigated
      105 M. kansasii cases in which IGRAs were performed before or ?14 days after
      treatment initiation. Clinical characteristics including a history of
      tuberculosis, radiographic features and laboratory data were collected from
      medical records. RESULTS: Positive rate of each IGRA was 25.9% (15/58) in
      QuantiFERON TB-Gold (QFT-G), 31.8% (7/22) in QuantiFERON-TB Gold In Tube (QFT
      GIT), and 33.3% (7/21) in T-SPOT. TB (T-SPOT). After excluding cases having a
      history of tuberculosis, positive rate of each IGRA decreased to 19% (8/42) in
      QFT-G, 20% (3/15) in QFT-GIT, and 18.8% (3/16) in T-SPOT. The multivariate
      analysis revealed that only previous tuberculosis was significantly associated
      with positive IGRAs (odds ratio, 4.758; 95% confidence interval, 1.73-13.05; p =
      0.002). CONCLUSIONS: Positive rates of IGRAs were low in patients with M.
      kansasii, especially in those without previous tuberculosis. M. kansasii
      pulmonary infection alone might induce less interferon-gamma production with the
      antigens.

PMID- 27025205
TI  - Galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive
      aspergillosis in non-hematological patients.
AB  - BACKGROUND: The role of galactomannan (GM) in serum or bronchoalveolar lavage
      fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) has been
      extensively evaluated in hematological patients, however its performance in non
      hematological patients is not well established. METHODS: We performed a
      multicenter retrospective study in 3 university hospitals in Madrid, Spain
      between 2010 and 2014. The study population comprised patients with chronic
      obstructive pulmonary disease (COPD) and patients with immunosuppressive
      conditions in whom IPA was suspected and for whom BALF GM was available. Patients
      with hematological disorders were excluded. RESULTS: A total of 188 patients (35
      with COPD and 153 with immunosuppressive conditions) were analyzed, and 31 cases
      of IPA (proven or probable) were identified. The global sensitivity of BALF GM
      (optical density index [ODI] >= 1.0) was 77.4%; sensitivity was higher in
      patients with immunosuppressive conditions than in patients with COPD (81.8% vs
      66.7%; p: 0.38). In COPD patients, the best performance was obtained for BALF GM
      (ODI >= 0.5), although sensitivity (88.9%) was similar to that of BALF fungal
      culture (88.9%). The sensitivity of GM in serum was very poor in both populations
      (36.4% and 11.6%, respectively). CONCLUSIONS: In the present series, the
      diagnostic performance of BALF GM was good for IPA in non-hematological patients,
      especially in patients with immunosuppressive conditions.

PMID- 27025206
TI  - Differences between culture & non-culture confirmed invasive meningococci with a
      focus on factor H-binding protein distribution.
AB  - OBJECTIVES: To compare the distribution of capsular groups and factor H-binding
      protein (fHBP) variants among meningococcal isolates and non-culture clinical
      specimens and to assess the representativeness of group B isolates amongst group
      B cases as a whole. METHODS: A PCR sequencing assay was used to characterise fHBP
      from non-culture cases confirmed from January 2011 to December 2013. These were
      compared to genotypic data derived from whole genome analysis of isolates
      received during the same period. RESULTS: Group W and Y strains were more common
      among isolates than non-culture strains. The distribution of fHBP variants among
      group B non-culture cases generally reflected that seen in the corresponding
      isolates. Nonetheless, the non-culture subset contained a greater proportion of
      fHBP variant 15/B44, associated with the ST-269 cluster sublineage. CONCLUSIONS:
      Differences in capsular group and fHBP distribution among culture and non-culture
      cases may be indicative of variation in strain viability, diagnostic practice,
      disease severity and/or clinical presentation. Future analyses combining clinical
      case information with laboratory data may help to further explore these
      differences. Group B isolates provide a good representation of group B disease in
      E&W and, therefore, can reliably be used in fHBP strain coverage predictions of
      recently-licensed vaccines.

PMID- 27025207
TI  - Commentary on: Sleep disordered breathing and the risk of psoriasis among US
      women.

PMID- 27025208
TI  - Clinical studies in dermatology require a post-treatment observation phase to
      define the impact of the intervention on the natural history of the complaint.
AB  - The use of a post-treatment period of observation or "regression phase" is common
      in pharmaceutical and cosmetic clinical dermatology studies. Regression phases
      can be incorporated into a variety of study designs, ranging from simple post
      treatment observation for a defined period, as has been used for moisturizers,
      antidandruff formulations, and treatments for acne, to more complex randomized
      intermittent-treatment designs, as used in studies of psoriasis
      pharmacotherapies. Extensive information can be derived from a regression phase.
      Notably, it can provide useful data on the persistence of effect and time to
      relapse after treatment cessation, which are particularly relevant to skin
      conditions in which consumer or patient adherence to treatment is suboptimal. By
      incorporating a regression phase, a clinical study can more closely reflect "real
      world" behavior, e.g., the switching by consumers from antidandruff to beauty
      shampoos. The regression phase can also help to differentiate between products
      that show similar effectiveness during the treatment phase, and monitoring post
      treatment physiological end points can provide valuable evidence on the safety
      and mechanism of action of the therapy. 

PMID- 27025209
TI  - Additive-free harvesting of oleaginous phagotrophic microalga by oil and air
      flotation.
AB  - A unique oleaginous phagotrophic microalga Ochromonas danica is poised for
      effective lipid production from waste. Cell harvesting and dewatering are major
      costs in making algae-based products. In this work an effective additive-free
      harvesting method was developed, taking advantage of O. danica's comparatively
      more hydrophobic surface and larger size. The algal cells' partitioning to
      oil/water interface was evaluated. Recovery by flotation with waste cooking oil
      was optimized using an L-9 Taguchi orthogonal-array design. Further, additive
      free cell collection and concentrating by air flotation was studied for the
      effects of both physical factors (column dimension, air-stone pore size, sample
      to-column volume ratio) and culture properties (pH, culture growth stage, cell
      concentration, and pure versus impure cultures). The optimized process
      consistently achieved >90 % recovery in a single stage. 98+ % recovery could be
      achieved when starting concentrations were >10(8) cells/ml, or potentially using
      a two- or multi-stage process for diluter cultures. 

PMID- 27025210
TI  - Nucleic acid detection in the diagnosis and prevention of schistosomiasis.
AB  - Schistosomiasis is an important zoonotic parasitic disease that causes serious
      harms to humans and animals. Surveillance and diagnosis play key roles in
      schistosomiasis control, however, current techniques for surveillance and
      diagnosis of the disease have limitations. As genome data for parasites are
      increasing, novel techniques for detection incorporating nucleotide sequences are
      receiving widespread attention. These sensitive, specific, and rapid detection
      methods are particularly important in the diagnosis of low-grade and early
      infections, and may prove to have clinical significance. This paper reviews the
      progress of nucleic acid detection in the diagnosis and prevention of
      schistosomiasis, including such aspects as the selection of target genes, and
      development and application of nucleic acid detection methods. 

PMID- 27025212
TI  - Incidence of microcracks in maxillary first premolars after instrumentation with
      three different mechanized file systems: a comparative ex vivo study.
AB  - OBJECTIVES: The objective of this study is to determine the potential for
      microcracks in the radicular dentin of first maxillary premolars using three
      different mechanized endodontic instrumentation systems. METHODS: Eighty
      extracted maxillary first premolars with two root canals and no externally
      visible microcracks were selected. Root canal instrumentation was performed with
      either the ProTaper file system, the WaveOne primary file, or the self-adjusting
      file (SAF). Teeth with intact roots served as controls. The roots were cut into
      segments and examined with an intensive, small-diameter light source that was
      applied diagonally to the entire periphery of the root slice under *20
      magnification; the presence of microcracks and fractures was recorded. Pearson's
      chi-square method was used for statistical analysis, and significance was set at
      p < 0.05. RESULTS: Microcracks were present in 30 and 20 % of roots treated with
      the ProTaper and WaveOne systems, respectively, while no microcracks were present
      in the roots treated with the SAF (p = 0.008 and p = 0.035, respectively). Intact
      teeth presented with cracks in 5 % of the roots. The intensive, small-diameter
      light source revealed microcracks that could not be detected when using the
      microscope's light alone. CONCLUSIONS: Within the limitations of this study, it
      could be concluded that mechanized root canal instrumentation with the ProTaper
      and WaveOne systems in maxillary first premolars causes microcracks in the
      radicular dentin, while the use of the SAF file causes no such microcracks.
      CLINICAL RELEVANCE: Rotary and reciprocating files with large tapers may cause
      microcracks in the radicular dentin of maxillary first premolars. Less aggressive
      methods should be considered for these teeth.

PMID- 27025213
TI  - Perception of straightness and parallelism with minimal distance information.
AB  - The ability of human observers to judge the straightness and parallelism of
      extended lines has been a neglected topic of study since von Helmholtz's initial
      observations 150 years ago. He showed that there were significant misperceptions
      of the straightness of extended lines seen in the peripheral visual field. The
      present study focused on the perception of extended lines (spanning 90 degrees 
      visual angle) that were directly fixated in the visual environment of a
      planetarium where there was only minimal information about the distance to the
      lines. Observers were asked to vary the curvature of 1 or more lines until they
      appeared to be straight and/or parallel, ignoring any perceived curvature in
      depth. When the horizon between the ground and the sky was visible, the results
      showed that observers' judgements of the straightness of a single line were
      significantly biased away from the veridical, great circle locations, and towards
      equal elevation settings. Similar biases can be seen in the jet trails of
      aircraft flying across the sky and in Rogers and Anstis's new moon illusion
      (Perception, 42(Abstract supplement) 18, 2013, 2016). The biasing effect of the
      horizon was much smaller when observers were asked to judge the straightness and
      parallelism of 2 or more extended lines. We interpret the results as showing
      that, in the absence of adequate distance information, observers tend to perceive
      the projected lines as lying on an approximately equidistant, hemispherical
      surface and that their judgements of straightness and parallelism are based on
      the perceived separation of the lines superimposed on that surface.

PMID- 27025211
TI  - Bone Marrow-Derived Stem Cells: a Mixed Blessing in the Multifaceted World of
      Diabetic Complications.
AB  - Diabetes is one of the main economic burdens in health care, which threatens to
      worsen dramatically if prevalence forecasts are correct. What makes diabetes
      harmful is the multi-organ distribution of its microvascular and macrovascular
      complications. Regenerative medicine with cellular therapy could be the dam
      against life-threatening or life-altering complications. Bone marrow-derived stem
      cells are putative candidates to achieve this goal. Unfortunately, the bone
      marrow itself is affected by diabetes, as it can develop a microangiopathy and
      neuropathy similar to other body tissues. Neuropathy leads to impaired stem cell
      mobilization from marrow, the so-called mobilopathy. Here, we review the role of
      bone marrow-derived stem cells in diabetes: how they are affected by compromised
      bone marrow integrity, how they contribute to other diabetic complications, and
      how they can be used as a treatment for these. Eventually, we suggest new tactics
      to optimize stem cell therapy. 

PMID- 27025214
TI  - Does Sexual Conflict between Mother and Father Lead to Fertility Decline? : A
      Questionnaire Survey in a Modern Developed Society.
AB  - Fertility decline is a great challenge to evolutionary approaches to human
      behavior. In this study, we apply the perspective of sexual conflict between
      mother and father to the fertility decline. We predict that, under serial
      monogamy allowing for mate changes, the ideal number of children for women should
      be smaller than that for men, because the cost of reproduction for women should
      be higher than that for men. Our reasoning is that if the cost of child-bearing
      and child-rearing is higher for women than men, and if women, who therefore would
      want a smaller number of children than their husbands, have gained more power in
      reproductive decision-making within a couple owing to the modernization of
      society, fertility should decline. Until now, few evolutionary studies have
      analyzed empirical data in modern developed societies with such a perspective.
      Our questionnaire survey in an urban area in Japan revealed that mothers did
      experience greater cost during childcare than fathers. However, in contrast to
      our prediction, we found no sex differences in the ideal number of children
      between mothers and their husbands in many cases. About 60% of parents remembered
      wanting two children when they were childless. Moreover, mothers and their
      husbands had equal power in their decision-making regarding having children.
      After presenting these results, we discuss some perspectives to advance our
      understanding of fertility decline in terms of sexual conflict. 

PMID- 27025215
TI  - The ethics of animal research: a survey of the public and scientists in North
      America.
AB  - BACKGROUND: To determine whether the public and scientists consider common
      arguments (and counterarguments) in support (or not) of animal research (AR)
      convincing. METHODS: After validation, the survey was sent to samples of public
      (Sampling Survey International (SSI; Canadian), Amazon Mechanical Turk (AMT; US),
      a Canadian city festival and children's hospital), medical students (two second
      year classes), and scientists (corresponding authors, and academic
      pediatricians). We presented questions about common arguments (with their
      counterarguments) to justify the moral permissibility (or not) of AR. Responses
      were compared using Chi-square with Bonferonni correction. RESULTS: There were
      1220 public [SSI, n = 586; AMT, n = 439; Festival, n = 195; Hospital n = 107],
      194/331 (59%) medical student, and 19/319 (6%) scientist [too few to report]
      responses. Most public respondents were <45 years (65%), had some
      College/University education (83%), and had never done AR (92%). Most public and
      medical student respondents considered 'benefits arguments' sufficient to justify
      AR; however, most acknowledged that counterarguments suggesting alternative
      research methods may be available, or that it is unclear why the same 'benefits
      arguments' do not apply to using humans in research, significantly weakened
      'benefits arguments'. Almost all were not convinced of the moral permissibility
      of AR by 'characteristics of non-human-animals arguments', including that non
      human-animals are not sentient, or are property. Most were not convinced of the
      moral permissibility of AR by 'human exceptionalism' arguments, including that
      humans have more advanced mental abilities, are of a special 'kind', can enter
      social contracts, or face a 'lifeboat situation'. Counterarguments explained much
      of this, including that not all humans have these more advanced abilities
      ['argument from species overlap'], and that the notion of 'kind' is arbitrary
      [e.g., why are we not of the 'kind' 'sentient-animal' or 'subject-of-a-life'?].
      Medical students were more supportive (80%) of AR at the end of the survey (p <
      0.05). CONCLUSIONS: Responses suggest that support for AR may not be based on
      cogent philosophical rationales, and more open debate is warranted.

PMID- 27025216
TI  - Surgical correction of persistent truncus arteriosus on a 33-year-old male with
      unilateral pulmonary hypertension from migration of pulmonary artery band.
AB  - BACKGROUND: Persistent truncus arteriosus is a rare congenital condition with
      which survival into adulthood is dismal without surgery. This is the oldest
      patient reported to our knowledge demonstrating the feasibility of assessing
      operability in persistent truncus arteriosus with unilateral pulmonary stenosis,
      and performing full corrective surgery in adulthood. CASE PRESENTATION: We report
      a Chinese male with successful correction of Type I persistent truncus arteriosus
      at 33 years of age. He had unilateral pulmonary hypertension from migration of
      pulmonary artery band from the main to the right pulmonary artery, severe truncal
      valve regurgitation from previous infective endocarditis, and progressive
      congestive heart failure. Improvement of lung perfusion was demonstrated 21
      months post operation. CONCLUSION: This case demonstrated that in patients with
      persistent truncus arteriosus and two pulmonary arteries, pulmonary vascular
      disease or underdevelopment of one lung does not preclude a full corrective
      surgery so long as the other vascular bed is normal. It is important to emphasize
      the importance of assessing patient's operability in totality.

PMID- 27025217
TI  - A Rare Case of Retained Foreign Material in the Pelvicalyceal System
      Precipitating Sepsis Following Percutaneous Nephrostomy.

PMID- 27025218
TI  - [Effect of the German Act on the reform of the market for medicinal products
      (AMNOG) on the quality of neurological and psychiatric treatment].

PMID- 27025219
TI  - Cadmium uptake by Carpobrotus rossii (Haw.) Schwantes under different saline
      conditions.
AB  - Plants used for phytoextraction of heavy metals from contaminated soils with high
      levels of salinity should be able to accumulate heavy metals and also be tolerant
      to salinity. Australian native halophyte species Carpobrotus rossii has recently
      been shown to tolerate and accumulate multiple heavy metals, especially cadmium
      (Cd). This study examined the effects of salt type and concentration on
      phytoextraction of Cd in C. rossii. Plants were grown in contaminated soil for 63
      days. The addition of salts increased plant growth and enhanced the accumulation
      of Cd in shoots up to 162 mg kg(-1) which almost doubled the Cd concentration (87
      mg kg(-1)) in plants without salt addition. The increased Cd accumulation was
      ascribed mainly to increased ionic strength in soils due to the addition of salts
      and resultantly increased the mobility of Cd. In comparison, the addition of Cl(
      ) resulted in 8-60 % increase in Cd accumulation in shoots than the addition of
      SO4 (2-) and NO3 (-). The findings suggest that C. rossii is a promising
      candidate in phytoextraction of Cd-polluted soils with high salinity levels. 

PMID- 27025220
TI  - Soil characterization and differential patterns of heavy metal accumulation in
      woody plants grown in coal gangue wastelands in Shaanxi, China.
AB  - Soil contamination by heavy metals in coal mine wastelands is a significant
      environmental issue in most developing countries. The purpose of this study is to
      evaluate contamination characteristics in the coal mine wastelands of Sanlidong
      coal mine, Tongchuan, China. To achieve this goal, we conducted field sampling
      work, followed by further analysis of the properties of soil contamination and
      accumulation characteristics in woody plants. At this site, the pH value ranged
      from 4.41 to 7.88, and the nutrient content of the soil rose gradually with the
      time after deposition due to the weathering effect improving the soil quality.
      Meanwhile, the levels of Cd, Cr, Cu, Ni, and Zn gradually decreased with the
      passage time. Generally, heavy metal contamination was found to be more serious
      in the discharge refuse area, with Cd contamination at moderate or heavy levels;
      Ni, Zn, and Cu contamination at light levels; and with no Cr contamination. The
      geoaccumulation index (I geo) was highest for Cd (2.38-3.14), followed by Ni, Zn,
      Cu, and Cr. Heavy metals accumulated on the lower slopes and spread to the
      surrounding areas via hydrodynamic effects and wind. According to transfer and
      enrichment coefficient analyses, Robinia pseudoacacia, Ulmus pumila, and
      Hippophae rhamnoides with considerable biomass could be used as pollution
      resistant tree species for vegetation restoration. This study provided a
      theoretical basis for the restoration of the ecological environment in the mining
      area. This report described a link between heavy metal contamination of soils and
      growth dynamics of woody plants in China. 

PMID- 27025221
TI  - Dynamic network modelling to understand flowering transition and floral
      patterning.
AB  - Differentiation and morphogenetic processes during plant development are
      particularly robust. At the cellular level, however, plants also show great
      plasticity in response to environmental conditions, and can even reverse
      apparently terminal differentiated states with remarkable ease. Can we understand
      and predict both robust and plastic systemic responses as a general consequence
      of the non-trivial interplay between intracellular regulatory networks, extrinsic
      environmental signalling, and tissue-level mechanical constraints? Flower
      development has become an ideal model system to study these general questions of
      developmental biology, which are especially relevant to understanding stem cell
      patterning in plants, animals, and human disease. Decades of detailed study of
      molecular developmental genetics, as well as novel experimental techniques for in
      vivo assays in both wild-type and mutant plants, enable the postulation and
      testing of experimentally grounded mathematical and computational network
      dynamical models. Research in our group aims to explain the emergence of robust
      transitions that occur at the shoot apical meristem, as well as flower
      development, as the result of the collective action of key molecular components
      in regulatory networks subjected to intra-organismal signalling and extracellular
      constraints. Here we present a brief overview of recent work from our group, and
      that of others, focusing on the use of simple dynamical models to address cell
      fate specification and cell-state stochastic dynamics during flowering transition
      and cell-state transitions at the shoot apical meristem of Arabidopsis thaliana.
      We also focus on how our work fits within the general field of plant
      developmental modelling, which is being developed by many others.

PMID- 27025222
TI  - Nutritional Concepts and Frequency of Foodstuffs Mentioned in the Holy Quran.
AB  - The Holy Quran is a religious book of Muslims. In many verses of Quran, various
      foods are discussed. It seems that limited studies were performed on
      identification the nutritional verses and their frequencies in the Holy Quran.
      Therefore, the aims of present study were to establish a numerical model system
      for studying nutritional verses of Quran, determination of verses with
      nutritional concepts and frequency of foodstuffs in the Holy Quran. In this
      descriptive analytical study, "Ghamoos e Quran" and "Vazheyab" online softwares
      were used to determine the nutritional keywords in Quran. For searching,
      translating, and interpretation of verses, "Noor-e-Jami Tafasir version 2.1";
      "Zekr" and "Pars Quran"softwares were applied. Sixty-four nutritional keywords
      and 257 nutritional verses were identified. Findings indicated that
      aliment/foods, eating, water/drinking words, and their derivatives are repeated
      171, 109, and 131 times in the Holy Quran, respectively. According to the Holy
      Quran, except Haram foods (pork meat, wine, carrion meat, blood, and meat of
      animals not slaughtered properly in the Islamic manner), all foods are tayyeb
      (lawful). The Holy Quran contains many foodstuffs and verses with nutritional
      concepts and it recommends eating varied and balanced diet. 

PMID- 27025223
TI  - Morbidity, mortality, associated injuries, and management of traumatic rib
      fractures.
AB  - BACKGROUND: Thoracic trauma is responsible for approximately 25% of trauma
      deaths, and rib fractures are present in as many as 40-80% of patients, and
      intensive care and/or ventilator support are frequently required for these
      patients. To identify their risk factors would improve treatment strategies for
      these patients. METHODS: Between March 2005 and December 2013, consecutive
      patients with blunt thoracic trauma, who were admitted to the Department of
      Thoracic Surgery at Tungs' Taichung Metro Harbor Hospital (Taichung, Taiwan),
      were reviewed in this retrospective cohort study with the approval of the
      Institutional Review Board. The duration of hospital stay, ventilator support,
      injury severity score (ISS), type of injury, associated injuries, treatments, and
      mortality were analyzed statistically. RESULTS: A total of 1621 thoracic trauma
      patients were included in this study, with a male majority and an age range of 18
      95 years (mean age, 51.2 years). Approximately 11.7% of these patients had an ISS
      >= 16 and a mortality rate of 6.9%. Among them, 78.5% had rib fractures; 31.8%,
      traumatic hemothorax; 15.6%, pneumothorax; 9.6%, hemopneumothorax; and 4.6%, lung
      contusion. The most common associated injury was extremity fracture, followed by
      head injury and clavicle fracture. Surgery on the extremities (20.6% of patients)
      and chest tube placement (22.7% of patients) were the most common treatments. The
      number of rib fractures was associated with prolonged hospital and intensive care
      unit (ICU) stays (>=7 days), an ISS >= 16, and pulmonary complications of
      hemothorax, pneumothorax, and hemopneumothorax, but not with mechanical
      ventilator use. Furthermore, old age was significantly associated with rib
      fractures in patients with thoracic trauma. CONCLUSION: The severity of traumatic
      rib fractures was identified in this study. Therefore, a trauma team needs better
      preparation to provide effective treatment strategies when encountering thoracic
      trauma patients, especially patients who are older and have rib fractures.

PMID- 27025224
TI  - Open versus percutaneous release for trigger digits: Reversal between short-term
      and long-term outcomes.
AB  - BACKGROUND: There have been excellent outcomes reported with both open and
      percutaneous release of trigger finger. However, a comparison of short- and long
      term outcomes between these two techniques has not been performed. The purpose of
      this study is to compare the short-term (3 months) and long-term (2 years)
      outcomes between open surgical release and percutaneous needle release of trigger
      finger. METHODS: Between 2009 and 2012, a total of 198 patients with trigger
      finger treated with either open (n = 72) or percutaneous (n = 126) release of the
      A1 pulley were enrolled in the study. Both short-term and long-term outcomes were
      evaluated, using the criteria established through Gilberts et al's questionnaire.
      RESULTS: The short-term satisfaction of patients with their results was
      significantly better in the percutaneous release group, whereas the long-term
      satisfaction rates were better in the open-release group, although not at a
      statistically significant level. CONCLUSION: The percutaneous release method to
      release trigger finger does not have a better long-term satisfaction rate than
      the open release approach, although percutaneous release has a significantly
      better short-term satisfaction rate.

PMID- 27025225
TI  - High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor
      for adverse reactions in patients with pneumocystis pneumonia and AIDS.
AB  - BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the most
      effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in
      patients with AIDS. The major drawback is the frequent occurrence of adverse
      reactions (ADRs).The current study was designed to determine the frequency and
      risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS. METHODS:
      A retrospective study was conducted in adult patients with PJP and AIDS who were
      admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January
      2006 and December 2011. Charts were reviewed to determine the effect of age, risk
      behaviors, severity of illness, viral load, CD4 cell counts, use of
      corticosteroids, and dosage and duration of TMP/SMX on ADRs during
      hospitalization. Patients who received TMP/SMX for <= 5 days or with an
      incomplete medical record were excluded. Multivariate logistic regression was
      used to calculate the hazard ratio (HR) for ADRs. RESULTS: Fifty two of 75
      patients with PJP and AIDS met the study criteria. Of these patients, 21/52
      (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash
      was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated
      creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms
      in three (14.3%). Most of the ADRs occurred within the 1(st) 2 weeks of TMP/SMX
      therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX
      of >= 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40-10.35; p = 0.009) and age
      34 years (HR, 4.30; 95% confidence interval, 1.52-12.14; p = 0.006) were
      independently associated with ADRs. CONCLUSION: We found a high incidence of ADRs
      among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin
      and liver. A daily dose of >= 16 mg/kg of TMP/SMX and age 34 years were
      independent risk factors for ADRs.

PMID- 27025226
TI  - Overexpression of SlUPA-like induces cell enlargement, aberrant development and
      low stress tolerance through phytohormonal pathway in tomato.
AB  - upa20 induces cell enlargement and hypertrophy development. In our research,
      overexpression of SlUPA-like, orthologous to upa20, severely affected the growth
      of vegetative and reproductive tissues. Wilted leaves curled upwardly and sterile
      flowers were found in transgenic lines. Through anatomical analysis, palisade and
      spongy tissues showed fluffy and hypertrophic development in transgenic plants.
      Gene expression analysis showed that GA responsive, biosynthetic and signal
      transduction genes (e.g. GAST1, SlGA20OXs, SlGA3OXs, SlGID1s, and SlPREs) were
      significantly upregulated, indicating that GA response is stimulated by
      overproduction of SlUPA-like. Furthermore, SlUPA-like was strongly induced by
      exogenous JA and wounding. Decreased expression of PI-I and induced expression of
      SlJAZs (including SlJAZ2, SlJAZ10 and SlJAZ11) were observed in transgenic
      plants, suggesting that JA response is repressed. In addition, SlUPA-like
      overexpressed plant exhibited more opened stoma and higher water loss than the
      control when treated with dehydration stress, which was related to decreased ABA
      biosynthesis, signal transduction and response. Particularly, abnormal
      developments of transgenic plants promote the plant susceptibility to Xanthomonas
      campestris pv. campestris. Therefore, it is deduced from these results that SlUPA
      like plays vital role in regulation of plant development and stress tolerance
      through GA, JA and ABA pathways. 

PMID- 27025228
TI  - Enhancing the Effectiveness of Consumer-Focused Health Information Technology
      Systems Through eHealth Literacy: A Framework for Understanding Users' Needs.
AB  - BACKGROUND: eHealth systems and applications are increasingly focused on
      supporting consumers to directly engage with and use health care services.
      Involving end users in the design of these systems is critical to ensure a
      generation of usable and effective eHealth products and systems. Often the end
      users engaged for these participatory design processes are not actual
      representatives of the general population, and developers may have limited
      understanding about how well they might represent the full range of intended
      users of the eHealth products. As a consequence, resulting information technology
      (IT) designs may not accommodate the needs, skills, cognitive capacities, and/or
      contexts of use of the intended broader population of health consumers. This may
      result in challenges for consumers who use the health IT systems, and could lead
      to limitations in adoption if the diversity of user attributes has not been
      adequately considered by health IT designers. OBJECTIVE: The objective of this
      paper is to propose how users' needs and competences can be taken into account
      when designing new information and communications technology solutions in health
      care by expanding the user-task-context matrix model with the domains of a new
      concept of eHealth literacy. METHODS: This approach expands an existing method
      for supporting health IT system development, which advocates use of a three
      dimensional user-task-context matrix to comprehensively identify the users of
      health IT systems, and what their needs and requirements are under differing
      contexts of use. The extension of this model involved including knowledge about
      users' competences within the seven domains of eHealth literacy, which had been
      identified based on systematic engagement with computer scientists, academics,
      health professionals, and patients recruited from various patient organizations
      and primary care. A concept map was constructed based on a structured brainstorm
      procedure, card sorting, and computational analysis. RESULTS: The new eHealth
      literacy concept (based on 7 domains) was incorporated as a key factor in
      expanding the user-task-context matrix to describe and qualify user requirements
      and understanding related to eHealth literacy. This resulted in an expanded
      framework and a five-step process, which can support health IT designers in
      understanding and more accurately addressing end-users' needs, capabilities, and
      contexts to improve effectiveness and broader applicability of consumer-focused
      health IT systems. It is anticipated that the framework will also be useful for
      policy makers involved in the planning, procuring, and funding of eHealth
      infrastructure, applications, and services. CONCLUSIONS: Developing effective
      eHealth products requires complete understanding of the end-users' needs from
      multiple perspectives. In this paper, we have proposed and detailed a framework
      for modeling users' needs for designing eHealth systems that merges prior work in
      development of a user-task-context matrix with the emerging area of eHealth
      literacy. This framework is intended to be used to guide design of eHealth
      technologies and to make requirements explicitly related to eHealth literacy,
      enabling a generation of well-targeted, fit-for-purpose, equitable, and effective
      products and systems.

PMID- 27025227
TI  - An embedded microretroreflector-based microfluidic immunoassay platform.
AB  - We present a microfluidic immunoassay platform based on the use of linear
      microretroreflectors embedded in a transparent polymer layer as an optical
      sensing surface, and micron-sized magnetic particles as light-blocking labels.
      Retroreflectors return light directly to its source and are highly detectable
      using inexpensive optics. The analyte is immuno-magnetically pre-concentrated
      from a sample and then captured on an antibody-modified microfluidic substrate
      comprised of embedded microretroreflectors, thereby blocking reflected light.
      Fluidic force discrimination is used to increase specificity of the assay,
      following which a difference imaging algorithm that can see single 3 MUm magnetic
      particles without optical calibration is used to detect and quantify signal
      intensity from each sub-array of retroreflectors. We demonstrate the utility of
      embedded microretroreflectors as a new sensing modality through a proof-of
      concept immunoassay for a small, obligate intracellular bacterial pathogen,
      Rickettsia conorii, the causative agent of Mediterranean Spotted Fever. The
      combination of large sensing area, optimized surface chemistry and microfluidic
      protocols, automated image capture and analysis, and high sensitivity of the
      difference imaging results in a sensitive immunoassay with a limit of detection
      of roughly 4000 R. conorii per mL.

PMID- 27025230
TI  - Infantile haemangiomas of the head and neck: current concepts in management.
AB  - Recent developments have improved our understanding of the clinical behaviour of
      haemangiomas and vascular malformations. In this paper, the second in a series of
      three educational reviews on vascular anomalies, we review the current trends and
      evidence-based management of infantile haemangiomas and their associated
      conditions. 

PMID- 27025229
TI  - Activity-dependent plasticity in the isolated embryonic avian brainstem following
      manipulations of rhythmic spontaneous neural activity.
AB  - When rhythmic spontaneous neural activity (rSNA) first appears in the embryonic
      chick brainstem and cranial nerve motor axons it is principally driven by
      nicotinic neurotransmission (NT). At this early age, the nicotinic acetylcholine
      receptor (nAChR) agonist nicotine is known to critically disrupt rSNA at low
      concentrations (0.1-0.5MUM), which are levels that mimic the blood plasma levels
      of a fetus following maternal cigarette smoking. Thus, we quantified the effect
      of persistent exposure to exogenous nicotine on rSNA using an in vitro
      developmental model. We found that rSNA was eliminated by continuous bath
      application of exogenous nicotine, but rSNA recovered activity within 6-12h
      despite the persistent activation and desensitization of nAChRs. During the
      recovery period rSNA was critically driven by chloride-mediated membrane
      depolarization instead of nicotinic NT. To test whether this observed
      compensation was unique to the antagonism of nicotinic NT or whether the loss of
      spiking behavior also played a role, we eliminated rSNA by lowering overall
      excitatory drive with a low [K(+)]o superfusate. In this context, rSNA again
      recovered, although the recovery time was much quicker, and exhibited a lower
      frequency, higher duration, and an increase in the number of bursts per episode
      when compared to control embryos. Importantly, we show that the main compensatory
      response to lower overall excitatory drive, similar to nicotinergic block, is a
      result of potentiated chloride mediated membrane depolarization. These results
      support increasing evidence that early neural circuits sense spiking behavior to
      maintain primordial bioelectric rhythms. Understanding the nature of
      developmental plasticity in the nervous system, especially versions that preserve
      rhythmic behaviors following clinically meaningful environmental stimuli, both
      normal and pathological, will require similar studies to determine the
      consequences of feedback compensation at more mature chronological ages.

PMID- 27025231
TI  - Endoscopically-assisted operations in the treatment of odontogenic peripheral
      osteomyelitis of the posterior mandible.
AB  - The aim of this study was to evaluate the possibility of using an endoscope in
      the treatment of five patients with odontogenic peripheral osteomyelitis of the
      posterior mandible diagnosed between March 2012 and September 2014. After imaging
      and general preoperative examination, the patients had endoscopically-assisted
      curettage and sequestrectomy. The data collected included the duration of the
      operation, complications, and patients' degree of satisfaction. The mean duration
      of the operation through an intraoral incision, was 46 (range 40-60) minutes.
      Patients were followed up at 1 week, 3 months, and 6 months, with no signs of
      recurrence. One patient reported postoperative swelling in the mandibular angle
      but this settled. The incision was minimal and left no postoperative scar on the
      face. All the patients recovered free of complications and were satisfied with
      the results of the operation. Because of the minimally-invasive intraoral
      incision, endoscopically-assisted treatment of odontogenic peripheral
      osteomyelitis of the posterior mandible can maintain external facial integrity
      without surgical scars. 

PMID- 27025232
TI  - Minimal-access technique for harvest of the radial forearm flap.

PMID- 27025233
TI  - Quality improvement- where do we stand?
AB  - Improvements in quality are commonly used to measure outcome in modern medicine.
      The drive to improve services nationally and to reduce the financial burden,
      which is at the forefront of NHS policy, attracts political debate and is
      constantly the focus of media attention. However, before this can be done in
      surgery, we need to learn from ongoing work and recognised systems for quality
      review and implementation, and develop national processes for sustained
      improvement. As a specialty, Oral and maxillofacial surgery is a good example. 

PMID- 27025234
TI  - Tooth-bone CAD/CAM surgical guide for genioplasty.

PMID- 27025235
TI  - Six synchronous bilateral parotid Warthin tumours: an unusual presentation.

PMID- 27025236
TI  - Use of the circular compression stapler and circular mechanical stapler in the
      end-to-side transanal colorectal anastomosis after left colon and rectal
      resections A single center experience.
AB  - AIM: The aim of our study was to compare the efficacy of the circular compression
      stapler and the circular mechanical stapler in transanal colorectal anastomosis
      after left colectomy or anterior rectal resection. MATERIALS AND METHODS: We
      performed a retrospective analysis of 10 patients with disease of the, sigmoid
      colon or rectum (carcinoma or diverticular disease) who underwent left colectomy
      or anterior rectal resection with end-to-side transanal colorectal anastomosis. A
      follow-up was planned for all patients at 1, 3 and 6 months after surgery and the
      anastomosis was evaluated by colonoscopy at 1 year. RESULTS: In all patients an
      end-to-side transanal colorectal anastomosis was performed using a circular
      compression stapler (CCS group) or circular mechanical staplers with titanium
      staples (CMS group). The mean distance of the anastomosis from the anal margin
      was 6.4 +/- 1.5 cm in the CCS group and 18.2 +/- 11.2 cm in the CMS group. All
      patients in the CCS group expelled the ring after a mean time of 8.2
      postoperative days. At 12 months colonoscopy revealed that all CCS patients had a
      satisfactory anastomosis with mean size of the colic lumen at the level of
      anastomotic line of 26.3 mm. CONCLUSIONS: In our experience the circular
      compression stapler a valuable alternative to the circular mechanical stapler for
      the creation of transanal colorectal anastomosis, in line with the relevant
      literature. KEY WORDS: Anastomotic leakage, Anastomotic stenosis, Circular
      compression stapler, Circular mechanical stapler, Transanal colorectal
      anastomosis.

PMID- 27025237
TI  - How Does Learnability of Primary Care Resident Physicians Increase After Seven
      Months of Using an Electronic Health Record? A Longitudinal Study.
AB  - BACKGROUND: Electronic health records (EHRs) with poor usability present steep
      learning curves for new resident physicians, who are already overwhelmed in
      learning a new specialty. This may lead to error-prone use of EHRs in medical
      practice by new resident physicians. OBJECTIVE: The study goal was to determine
      learnability gaps between expert and novice primary care resident physician
      groups by comparing performance measures when using EHRs. METHODS: We compared
      performance measures after two rounds of learnability tests (November 12, 2013 to
      December 19, 2013; February 12, 2014 to April 22, 2014). In Rounds 1 and 2, 10
      novice and 6 expert physicians, and 8 novice and 4 expert physicians
      participated, respectively. Laboratory-based learnability tests using video
      analyses were conducted to analyze learnability gaps between novice and expert
      physicians. Physicians completed 19 tasks, using a think-aloud strategy, based on
      an artificial but typical patient visit note. We used quantitative performance
      measures (percent task success, time-on-task, mouse activities), a system
      usability scale (SUS), and qualitative narrative feedback during the participant
      debriefing session. RESULTS: There was a 6-percentage-point increase in novice
      physicians' task success rate (Round 1: 92%, 95% CI 87-99; Round 2: 98%, 95% CI
      95-100) and a 7-percentage-point increase in expert physicians' task success rate
      (Round 1: 90%, 95% CI 83-97; Round 2: 97%, 95% CI 93-100); a 10% decrease in
      novice physicians' time-on-task (Round 1: 44s, 95% CI 32-62; Round 2: 40s, 95% CI
      27-59) and 21% decrease in expert physicians' time-on-task (Round 1: 39s, 95% CI
      29-51; Round 2: 31s, 95% CI 22-42); a 20% decrease in novice physicians mouse
      clicks (Round 1: 8 clicks, 95% CI 6-13; Round 2: 7 clicks, 95% CI 4-12) and 39%
      decrease in expert physicians' mouse clicks (Round 1: 8 clicks, 95% CI 5-11;
      Round 2: 3 clicks, 95% CI 1-10); a 14% increase in novice mouse movements (Round
      1: 9247 pixels, 95% CI 6404-13,353; Round 2: 7991 pixels, 95% CI 5350-11,936) and
      14% decrease in expert physicians' mouse movements (Round 1: 7325 pixels, 95% CI
      5237-10,247; Round 2: 6329 pixels, 95% CI 4299-9317). The SUS measure of overall
      usability demonstrated only minimal change in the novice group (Round 1: 69, high
      marginal; Round 2: 68, high marginal) and no change in the expert group (74; high
      marginal for both rounds). CONCLUSIONS: This study found differences in novice
      and expert physicians' performance, demonstrating that physicians' proficiency
      increased with EHR experience. Our study may serve as a guideline to improve
      current EHR training programs. Future directions include identifying usability
      issues faced by physicians when using EHRs, through a more granular task analysis
      to recognize subtle usability issues that would otherwise be overlooked.

PMID- 27025238
TI  - New treatments for hepatitis C virus (HCV): scope for preventing liver disease
      and HCV transmission in England.
AB  - New direct-acting antivirals have the potential to transform the hepatitis C
      (HCV) treatment landscape, with rates of sustained viral response in excess of
      90%. As these new agents are expensive, an important question is whether to focus
      on minimizing the consequences of severe liver disease, or reducing transmission
      via 'treatment as prevention'. A back-calculation model was used to estimate the
      impact of treatment of mild, moderate and compensated cirrhosis on incident cases
      of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In
      addition, a dynamic model was used to determine the impact on incidence and
      prevalence of chronic infection in people who inject drugs (PWID), the main risk
      group in England. Treating 3500 cirrhotics per year was predicted to reduce
      ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630
      (95% CrI 530-770) in 2020, around half that currently expected, although treating
      moderate-stage disease will also be needed to sustain this reduction. Treating
      mild-stage PWID was required to make a substantial impact on transmission: with
      2500 treated per year, chronic prevalence/annual incidence in PWID was reduced
      from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the
      two goals: treating mild stage had virtually no impact on ESLD/HCC within 15
      years, but the long timescale of liver disease means relatively few PWID reach
      cirrhosis before cessation of injecting. Strategies focussing on treating
      advanced disease have the potential for dramatic reductions in severe morbidity,
      but virtually no preventative impact.

PMID- 27025240
TI  - Circulating makorin ring finger protein 3 levels decline in boys before the
      clinical onset of puberty.
AB  - OBJECTIVE: Makorin ring finger protein 3 (MKRN3) gene restrains the hypothalamic
      pituitary-gonadal axis. In girls, peripheral levels of MKRN3 decline prior to the
      onset of puberty. We described longitudinal changes in serum MKRN3 levels in boys
      before and during puberty and assessed the effect of inhibition of estrogen
      biosynthesis on MKRN3 levels. DESIGN: Longitudinal serum samples from a double
      blind, randomized controlled study in 30 boys (age range: 9.1-14.2years) with
      idiopathic short stature who received placebo (Pl; n=14) or aromatase inhibitor
      letrozole (Lz; 2.5mg/day; n=16) for 2years. METHODS: We analyzed the
      relationships between serum MKRN3 and clinical and biochemical markers of puberty
      by using summary measures. RESULTS: Serum MKRN3 declined by 669+/-713 pg/mL per
      year (P<0.001). This change was biphasic, as the levels decreased during Tanner
      genital stage G1 (-2931+/-2750 pg/mL per year) and plateaued thereafter (-560+/
      1510 pg/mL per year) (P<0.05). During G1, MKRN3 levels in Lz-treated subjects
      decreased slower than in Pl-treated boys (-782+/-3190 vs -2030+/-821 pg/mL per
      year, P<0.05). The decrease in serum MKRN3 levels in G1 was associated with
      increases in LH (r=-0.5, P<0.01), testosterone (r=-0.6, P<0.01), and inhibin B
      (r=-0.44, P<0.05) (n=26). CONCLUSION: Peripheral MKRN3 levels in boys appear to
      serve as a readout of the diminishing central inhibition that controls the onset
      of puberty.

PMID- 27025239
TI  - Acute heart failure with cardiomyocyte atrophy induced in adult mice by ablation
      of cardiac myosin light chain kinase.
AB  - AIMS: Under pressure overload, initial adaptive hypertrophy of the heart is
      followed by cardiomyocyte elongation, reduced contractile force, and failure. The
      mechanisms governing the transition to failure are not fully understood. Pressure
      overload reduced cardiac myosin light chain kinase (cMLCK) by ~80% within 1 week
      and persists. Knockdown of cMLCK in cardiomyocytes resulted in reduced cardiac
      contractility and sarcomere disorganization. Thus, we hypothesized that acute
      reduction of cMLCK may be causative for reduced contractility and cardiomyocyte
      remodelling during the transition from compensated to decompensated cardiac
      hypertrophy. METHODS AND RESULTS: To mimic acute cMLCK reduction in adult hearts,
      the floxed-Mylk3 gene that encodes cMLCK was inducibly ablated in
      Mylk3(flox/flox)/merCremer mice (Mylk3-KO), and compared with two control mice
      (Mylk3(flox/flox) and Mylk3(+/+)/merCremer) following tamoxifen injection (50
      mg/kg/day, 2 consecutive days). In Mylk3-KO mice, reduction of cMLCK protein was
      evident by 4 days, with a decline to below the level of detection by 6 days. By 7
      days, these mice exhibited heart failure, with reduction of fractional shortening
      compared with those in two control groups (19.8 vs. 28.0% and 27.7%). Severely
      convoluted cardiomyocytes with sarcomeric disorganization, wavy fibres, and cell
      death were demonstrated in Mylk3-KO mice. The cardiomyocytes were also unable to
      thicken adaptively to pressure overload. CONCLUSION: Our results, using a new
      mouse model mimicking an acute reduction of cMLCK, suggest that cMLCK plays a
      pivotal role in the transition from compensated to decompensated hypertrophy via
      sarcomeric disorganization.

PMID- 27025241
TI  - Low-dose hydrocortisone replacement is associated with improved arterial
      stiffness index and blood pressure dynamics in severely adrenocorticotrophin
      deficient hypopituitary male patients.
AB  - OBJECTIVE: Increased cardiovascular and cerebrovascular morbidity and mortality
      in hypopituitary subjects may be linked to inappropriate glucocorticoid exposure;
      however, the pathophysiology remains unclear. We aimed to examine the effect of
      three commonly prescribed hydrocortisone (HC) regimens on vascular risk factors.
      DESIGN: An open crossover study randomising ten hypopituitary men with severe
      adrenocorticotrophic hormone deficiency to three HC dose regimens: dose A (20mg
      mane and 10mg tarde), dose B (10mg mane and 10mg tarde) and dose C (10mg mane and
      5mg tarde). METHODS: Following 6 weeks on each regimen, participants underwent 24
      h serum cortisol sampling, 24-h ambulatory blood pressure (BP) measurements,
      calculation of the Ambulatory Arterial Stiffness Index (AASI), oral glucose
      tolerance testing and fasting serum osteoprotegerin (OPG) sampling. RESULTS:
      There were no differences in 24-h BP between dose regimens and controls; however,
      low-dose HC replacement (dose C) was associated with the lowest AASI, indicating
      a less stiff arterial tree (P<0.05) compared with the other dose regimens. Loss
      of the physiologic nocturnal BP dip was more common in higher HC replacement
      regimens, although only significant for dose B compared with dose C (P=0.03).
      Twenty per cent of patients had abnormal glucose tolerance, but this was
      unrelated to dose regimen. OPG correlated strongly with 24-h BP in those on dose
      A only (r=0.65, P=0.04). CONCLUSION: Currently prescribed HC replacement doses do
      not result in significant differences in absolute BP levels or improvements in
      insulin sensitivity. However, lower HC doses may result in lower arterial
      stiffness and a more physiological nocturnal BP dip. Long-term studies are
      required to confirm these findings and evaluate their impact on vascular
      morbidity in this patient group.

PMID- 27025243
TI  - Effects of different seating equipment on postural control and upper extremity
      function in children with cerebral palsy.
AB  - BACKGROUND: Adaptive seating supports for cerebral palsy are recommended to
      develop and maintain optimum posture, and functional use of upper extremities.
      OBJECTIVES: To compare the effectiveness of different seating adaptations
      regarding postural alignment and related functions and to investigate the effects
      of these seating adaptations on different motor levels. STUDY DESIGN: Prospective
      study. METHODS: A total of 20 children with spastic cerebral palsy (Gross Motor
      Function Classification System 3-5) were included. Postural control and function
      (Seated Postural Control Measure, Sitting Assessment Scale) were measured in
      three different systems: standard chair, adjustable seating system and custom
      made orthosis. RESULTS: In results of all participants ungrouped, there was a
      significant difference in most parameters of both measurement tools in favor of
      custom-made orthosis and adjustable seating system when compared to standard
      chair ( p < 0.0017). There was a difference among interventions in most of the
      Seated Postural Control Measure results in Level 4 when subjects were grouped
      according to Gross Motor Function Classification System levels. A difference was
      observed between standard chair and adjustable seating system in foot control,
      arm control, and total Sitting Assessment Scale scores; and between standard
      chair and custom-made orthosis in trunk control, arm control, and total Sitting
      Assessment Scale score in Level 4. There was no difference in adjustable seating
      system and custom-made orthosis in Sitting Assessment Scale in this group of
      children ( p < 0.017). CONCLUSION: Although custom-made orthosis fabrication is
      time consuming, it is still recommended since it is custom made, easy to use, and
      low-cost. On the other hand, the adjustable seating system can be modified
      according to a patient's height and weight. Clinical relevance It was found that
      Gross Motor Function Classification System Level 4 children benefitted most from
      the seating support systems. It was presented that standard chair is sufficient
      in providing postural alignment. Both custom-made orthosis and adjustable seating
      system have pros and cons and the best solution for each will be dependent on a
      number of factors.

PMID- 27025242
TI  - Clear signals or mixed messages: inter-individual emotion congruency modulates
      brain activity underlying affective body perception.
AB  - The neural basis of emotion perception has mostly been investigated with single
      face or body stimuli. However, in daily life one may also encounter affective
      expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what
      way is brain activity modulated when several individuals express similar rather
      than different emotions? We investigated this question using an experimental
      design in which we presented two stimuli simultaneously, with same or different
      emotional expressions. We hypothesized that, in the case of two same-emotion
      stimuli, brain activity would be enhanced, while in the case of two different
      emotions, one emotion would interfere with the effect of the other. The results
      showed that the simultaneous perception of different affective body expressions
      leads to a deactivation of the amygdala and a reduction of cortical activity. It
      was revealed that the processing of fearful bodies, compared with different
      emotion bodies, relied more strongly on saliency and action triggering regions in
      inferior parietal lobe and insula, while happy bodies drove the occipito-temporal
      cortex more strongly. We showed that this design could be used to uncover
      important differences between brain networks underlying fearful and happy
      emotions. The enhancement of brain activity for unambiguous affective signals
      expressed by several people simultaneously supports adaptive behaviour in
      critical situations.

PMID- 27025244
TI  - Stratified cost-utility analysis of C-Leg versus mechanical knees: Findings from
      an Italian sample of transfemoral amputees.
AB  - BACKGROUND: The fitting rate of the C-Leg electronic knee (Otto-Bock, D) has
      increased steadily over the last 15 years. Current cost-utility studies, however,
      have not considered the patients' characteristics. OBJECTIVES: To complete a cost
      utility analysis involving C-Leg and mechanical knee users; "age at the time of
      enrollment," "age at the time of first prosthesis," and "experience with the
      current type of prosthesis" are assumed as non-nested stratification parameters.
      STUDY DESIGN: Cohort retrospective. METHODS: In all, 70 C-Leg and 57 mechanical
      knee users were selected. For each stratification criteria, we evaluated the cost
      utility of C-Leg versus mechanical knees by computing the incremental cost
      utility ratio, that is, the ratio of the "difference in cost" and the "difference
      in utility" of the two technologies. Cost consisted of acquisition, maintenance,
      transportation, and lodging expenses. Utility was measured in terms of quality
      adjusted life years, computed on the basis of participants' answers to the EQ-5D
      questionnaire. RESULTS: Patients over 40 years at the time of first prosthesis
      were the only group featuring an incremental cost-utility ratio (88,779 ?/quality
      adjusted life year) above the National Institute for Health and Care Excellence
      practical cost-utility threshold (54,120 ?/quality-adjusted live year): C-Leg
      users experience a significant improvement of "mobility," but limited outcomes on
      "usual activities," "self-care," "depression/anxiety," and reduction of
      "pain/discomfort." CONCLUSION: The stratified cost-utility results have relevant
      clinical implications and provide useful information for practitioners in
      tailoring interventions. Clinical relevance A cost-utility analysis that
      considered patients characteristics provided insights on the "affordability" of C
      Leg compared to mechanical knees. In particular, results suggest that C-Leg has a
      significant impact on "mobility" for first-time prosthetic users over 40 years,
      but implementation of specific low-cost physical/psychosocial interventions is
      required to retun within cost-utility thresholds.

PMID- 27025245
TI  - Revisiting the Topographic Anatomy of the Marginal Mandibular Branch of Facial
      Nerve Relating to the Surgical Approach.
AB  - BACKGROUND: The marginal mandibular branch (Mbr) of the facial nerve is
      vulnerable to damage during rhytidoplasty, surgical reduction of the mandibular
      angle, parotidectomy, and excision of the submandibular gland. OBJECTIVES: The
      authors sought to map the Mbr and determine the relationship between the number
      of Mbr offshoots and the course of the Mbr. METHODS: The Mbr was examined in 29
      hemifaces from 12 embalmed and 4 fresh cadavers (10 males, 6 females; mean age,
      73.7 years). RESULTS: The Mbr was located <=5 mm from the gonion (Go) in 24 of 29
      hemifaces (82.8%) and <=10 mm from the intersection of the facial artery and
      mandible (ie, FM) in 26 hemifaces (89.7%). In 16 hemifaces (55.2%), offshoots
      arose from the Mbr inferior to the mandible. The Mbr ran below the Go in 14
      hemifaces (48.3%) and ran below FM in 13 hemifaces (44.8%). Except for minute
      offshoots deep to the platysma, the Mbr was not found to pass >2 cm below the
      mandible. The mean (+/- standard deviation) quantity of Mbr offshoots was 1.5 (+/
      0.6). A greater number of offshoots was associated with a higher likelihood of
      an inferiorly located nerve. The Mbr proceeded under the lower border of the
      mandible in 13 hemifaces (44.8%) and reached the mandible at a mean distance of
      33.1+/-5.2 mm anterior to the Go. CONCLUSIONS: To avoid damaging the Mbr,
      surgical maneuvers should be positioned 4.5 cm anterior to the Go and 2 cm below
      the mandible.

PMID- 27025246
TI  - Response to "Commentary on: Total Composite Flap Facelift and the Deep-Plane
      Transition Zone: A Critical Consideration in SMAS-Release Midface Lifting".

PMID- 27025247
TI  - Commentary on: The Safe Labiaplasty: A Study of Nerve Density in Labia Minora and
      Its Implications.

PMID- 27025249
TI  - Emergence of a Large-Plaque Variant in Mice Infected with Coxsackievirus B3.
AB  - Coxsackieviruses are enteric viruses that frequently infect humans. To examine
      coxsackievirus pathogenesis, we orally inoculated mice with the coxsackievirus B3
      (CVB3) Nancy strain. Using HeLa cell plaque assays with agar overlays, we noticed
      that some fecal viruses generated plaques >100 times as large as inoculum
      viruses. These large-plaque variants emerged following viral replication in
      several different tissues. We identified a single amino acid change, N63Y, in the
      VP3 capsid protein that was sufficient to confer the large-plaque phenotype. Wild
      type CVB3 and N63Y mutant CVB3 had similar plaque sizes when agarose was used in
      the overlay instead of agar. We determined that sulfated glycans in agar
      inhibited plaque formation by wild-type CVB3 but not by N63Y mutant CVB3.
      Furthermore, N63Y mutant CVB3 bound heparin, a sulfated glycan, less efficiently
      than wild-type CVB3 did. While N63Y mutant CVB3 had a growth defect in cultured
      cells and reduced attachment, it had enhanced replication and pathogenesis in
      mice. Infection with N63Y mutant CVB3 induced more severe hepatic damage than
      infection with wild-type CVB3, likely because N63Y mutant CVB3 disseminates more
      efficiently to the liver. Our data reinforce the idea that culture-adapted
      laboratory virus strains can have reduced fitnessin vivo N63Y mutant CVB3 may be
      useful as a platform to understand viral adaptation and pathogenesis in animal
      studies. IMPORTANCE: Coxsackieviruses frequently infect humans, and although many
      infections are mild or asymptomatic, there can be severe outcomes, including
      heart inflammation. Most studies with coxsackieviruses and other viruses use
      laboratory-adapted viral strains because of their efficient replication in cell
      culture. We used a cell culture-adapted strain of CVB3, Nancy, to examine viral
      replication and pathogenesis in orally inoculated mice. We found that mice shed
      viruses distinct from input viruses because they formed extremely large plaques
      in cell culture. We identified a single mutation, VP3 N63Y, that was sufficient
      for large-plaque formation. N63Y mutant viruses have reduced glycan binding and
      replication in cell culture; however, they have enhanced replication and
      virulence in mice. We are now using N63Y mutant CVB3 as an improved system for
      viral pathogenesis studies.

PMID- 27025248
TI  - Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and
      Translation Machineries.
AB  - Infection with human cytomegalovirus (HCMV) profoundly affects cellular
      metabolism. Like in tumor cells, HCMV infection increases glycolysis, and glucose
      carbon is shifted from the mitochondrial tricarboxylic acid cycle to the
      biosynthesis of fatty acids. However, unlike in many tumor cells, where aerobic
      glycolysis is accompanied by suppression of mitochondrial oxidative
      phosphorylation, HCMV induces mitochondrial biogenesis and respiration. Here, we
      affinity purified mitochondria and used quantitative mass spectrometry to
      determine how the mitochondrial proteome changes upon HCMV infection. We found
      that the mitochondrial transcription and translation systems are induced early
      during the viral replication cycle. Specifically, proteins involved in biogenesis
      of the mitochondrial ribosome were highly upregulated by HCMV infection.
      Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV
      induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in
      mitochondrially encoded proteins and significantly impaired viral growth under
      bioenergetically restricting conditions. Our findings demonstrate how HCMV
      manipulates mitochondrial biogenesis to support its replication. IMPORTANCE:
      Human cytomegalovirus (HCMV), a betaherpesvirus, is a leading cause of morbidity
      and mortality during congenital infection and among immunosuppressed individuals.
      HCMV infection significantly changes cellular metabolism. Akin to tumor cells, in
      HCMV-infected cells, glycolysis is increased and glucose carbon is shifted from
      the tricarboxylic acid cycle to fatty acid biosynthesis. However, unlike in tumor
      cells, HCMV induces mitochondrial biogenesis even under aerobic glycolysis. Here,
      we have affinity purified mitochondria and used quantitative mass spectrometry to
      determine how the mitochondrial proteome changes upon HCMV infection. We find
      that the mitochondrial transcription and translation systems are induced early
      during the viral replication cycle. Specifically, proteins involved in biogenesis
      of the mitochondrial ribosome were highly upregulated by HCMV infection.
      Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV
      induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in
      mitochondrially encoded proteins and significantly impaired viral growth. Our
      findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its
      replication.

PMID- 27025250
TI  - Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L
      Activation.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly
      pathogenic human coronavirus to emerge since severe acute respiratory syndrome
      coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes
      that encode multiple accessory proteins that are not required for replication of
      the genome but are likely involved in pathogenesis. Evasion of host innate
      immunity through interferon (IFN) antagonism is a critical component of viral
      pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway
      activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L
      cleaves viral and host single-stranded RNA (ssRNA), which leads to translational
      arrest and subsequent cell death, preventing viral replication and spread. Here
      we report that MERS-CoV, a lineage CBetacoronavirus, and related bat CoV NS4b
      accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase
      L by enzymatically degrading 2',5'-oligoadenylate (2-5A), activators of RNase L.
      This is a novel function for NS4b, which has previously been reported to
      antagonize IFN signaling. NS4b proteins are distinct from lineage
      ABetacoronavirusPDEs and rotavirus gene-encoded PDEs, in having an amino-terminal
      nuclear localization signal (NLS) and are localized mostly to the nucleus.
      However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient
      to prevent activation of RNase L. Finally, this is the first report of an RNase L
      antagonist expressed by a human or bat coronavirus and provides a specific
      mechanism by which this occurs. Our findings provide a potential mechanism for
      evasion of innate immunity by MERS-CoV while also identifying a potential target
      for therapeutic intervention. IMPORTANCE: Middle East respiratory syndrome
      coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge
      since severe acute respiratory syndrome coronavirus (SARS-CoV). MERS-CoV, like
      other coronaviruses, carries genes that encode accessory proteins that antagonize
      the host antiviral response, often the type I interferon response, and contribute
      to virulence. We found that MERS-CoV NS4b and homologs from related lineage C bat
      betacoronaviruses BtCoV-SC2013 (SC2013) and BtCoV-HKU5 (HKU5) are members of the
      2H-phosphoesterase (2H-PE) enzyme family with phosphodiesterase (PDE) activity.
      Like murine coronavirus NS2, a previously characterized PDE, MERS NS4b, can
      antagonize activation of the OAS-RNase L pathway, an interferon-induced potent
      antiviral activity. Furthermore, MERS-CoV mutants with deletion of genes encoding
      accessory proteins NS3 to NS5 or NS4b alone or inactivation of the PDE can
      activate RNase L during infection of Calu-3 cells. Our report may offer a
      potential target for therapeutic intervention if NS4b proves to be critical to
      pathogenesis inin vivomodels of MERS-CoV infection.

PMID- 27025251
TI  - Transfer of Viral Communities between Human Individuals during Fecal Microbiota
      Transplantation.
AB  - Fecal microbiota transplantation (FMT) is a highly effective treatment for
      refractoryClostridium difficileinfections. However, concerns persist about
      unwanted cotransfer of pathogenic microbes such as viruses. Here we studed FMT
      from a single healthy human donor to three pediatric ulcerative colitis patients,
      each of whom received a course of 22 to 30 FMT treatments. Viral particles were
      purified from donor and recipient stool samples and sequenced; the reads were
      then assembled into contigs corresponding to viral genomes or partial genomes.
      Transfer of selected viruses was confirmed by quantitative PCR. Viral contigs
      present in the donor could be readily detected in recipients, with up to 32
      different donor viral contigs appearing in a recipient sample. Reassuringly, none
      of these were viruses are known to replicate on human cells. Instead, viral
      contigs either scored as bacteriophage or could not be attributed taxonomically,
      suggestive of unstudied phage. The two most frequently transferred gene types
      were associated with temperate-phage replication. In addition, members
      ofSiphoviridae, the group of typically temperate phages that includes phage
      lambda, were found to be transferred with significantly greater efficiency than
      other groups. On the basis of these findings, we propose that the temperate-phage
      replication style may promote efficient phage transfer between human individuals.
      In summary, we documented transfer of multiple viral lineages between human
      individuals through FMT, but in this case series, none were from viral groups
      known to infect human cells. IMPORTANCE: Transfer of whole communities of viruses
      between humans has rarely been studied but is of likely medical importance. Here
      we studied fecal microbiota transplantation (FMT), a highly successful treatment
      for relapsingClostridium difficileinfection and, potentially, other
      gastrointestinal (GI) diseases. We investigated the transfer of viral communities
      during FMT and documented transfer of multiple viral lineages between humans.
      None of these were viruses that replicated on animal cells or that are known to
      be pathogenic. We found that temperate bacteriophage, which form stable
      associations with their hosts, were significantly more likely to be transferred
      during FMT. This supports a model in which the viral temperate replication style
      may have evolved in part to support efficient viral transmission between
      environments.

PMID- 27025252
TI  - HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA
      Cap-Binding Complex.
AB  - Stress granules (SGs) are dynamic accumulations of stalled preinitiation
      complexes and translational machinery that assemble under stressful conditions.
      Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ
      in morphology, composition, and mechanism of assembly from canonical SGs. Se
      inhibits translation initiation by altering the cap-binding activity of
      eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In
      this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able
      to block the assembly of type II noncanonical SGs to facilitate continued Gag
      protein synthesis. We demonstrate that expression of Gag reduces the amount of
      hypophosphorylated 4EBP1 associated with the 5' cap potentially through an
      interaction with its target, eIF4E. These results suggest that the assembly of
      SGs is an important host antiviral defense that HIV-1 has evolved for inhibition
      through several distinct mechanisms. IMPORTANCE: The antiviral stress response is
      an important host defense that many viruses, including HIV-1, have evolved to
      evade. Selenite induces a block in translation and leads to stress granule
      assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1.
      In this work, we demonstrate that in the face of selenite-induced stress, HIV-1
      is able to maintain Gag mRNA translation and to elicit a blockade to selenite
      induced stress granule assembly by altering the amount of hypophosphorylated
      4EBP1 on the 5' cap.

PMID- 27025254
TI  - Testing Usability and Acceptability of a Web Application to Promote Physical
      Activity (iCanFit) Among Older Adults.
AB  - BACKGROUND: Most older Americans do not exercise regularly and many have chronic
      conditions. Among an increasing number of fitness mobile and Web apps, few are
      designed for older adults with chronic conditions despite high ownership rates of
      mobile tools and Internet access in this population. We designed a mobile-enabled
      Web app, iCanFit, to promote physical activity in this population. OBJECTIVE:
      This study aimed to test the usability and acceptability of iCanFit among older
      adults in a community setting. METHODS: A total of 33 older adults (aged 60 to 82
      years) were recruited from communities to test iCanFit. Of these 33, 10
      participants completed the usability testing in a computer room of a senior
      community center. A research assistant timed each Web application task and
      observed user navigation behavior using usability metrics. The other 23
      participants used the website on their own devices at home and provided feedback
      after 2-3 weeks by completing a user-experience survey assessing ease of use,
      helpfulness, and satisfaction with iCanFit. RESULTS: Participants completed all
      15 tasks on the iCanFit site in an average of 31 (SD 6.9) minutes; some tasks
      required more time or needed assistance. Participants' comments were addressed to
      improve the site's senior friendliness and ease of use. In the user-experience
      survey, participants reported high levels of usefulness and satisfaction. More
      than 56% (13/23) of participants indicated they would continue using the program
      and recommend it to their families or friends. CONCLUSIONS: Testing usability and
      acceptability is a very important step in developing age-appropriate and user
      friendly Web apps, especially for older adults. Testing usability and
      acceptability in a community setting can help reveal users' experiences and
      feedback in a real-life setting. Our study suggested that older adults had a high
      degree of acceptance of iCanFit and could use it easily. The efficacy trial of
      iCanFit is currently underway.

PMID- 27025253
TI  - Mechanisms Underlying the Delayed Activation of the Cap1 Transcription Factor in
      Candida albicans following Combinatorial Oxidative and Cationic Stress Important
      for Phagocytic Potency.
AB  - Following phagocytosis, microbes are exposed to an array of antimicrobial weapons
      that include reactive oxygen species (ROS) and cationic fluxes. This is
      significant as combinations of oxidative and cationic stresses are much more
      potent than the corresponding single stresses, triggering the synergistic killing
      of the fungal pathogenCandida albicansby "stress pathway interference."
      Previously we demonstrated that combinatorial oxidative plus cationic stress
      triggers a dramatic increase in intracellular ROS levels compared to oxidative
      stress alone. Here we show that activation of Cap1, the major regulator of
      antioxidant gene expression inC. albicans, is significantly delayed in response
      to combinatorial stress treatments and to high levels of H2O2 Cap1 is normally
      oxidized in response to H2O2; this masks the nuclear export sequence, resulting
      in the rapid nuclear accumulation of Cap1 and the induction of Cap1-dependent
      genes. Here we demonstrate that following exposure of cells to combinatorial
      stress or to high levels of H2O2, Cap1 becomes trapped in a partially oxidized
      form, Cap1(OX-1) Notably, Cap1-dependent gene expression is not induced when Cap1
      is in this partially oxidized form. However, while Cap1(OX-1)readily accumulates
      in the nucleus and binds to target genes following high-H2O2stress, the nuclear
      accumulation of Cap1(OX-1)following combinatorial H2O2and NaCl stress is delayed
      due to a cationic stress-enhanced interaction with the Crm1 nuclear export
      factor. These findings define novel mechanisms that delay activation of the Cap1
      transcription factor, thus preventing the rapid activation of the stress
      responses vital for the survival ofC. albicanswithin the host. IMPORTANCE:
      Combinatorial stress-mediated synergistic killing represents a new unchartered
      area in the field of stress signaling. This phenomenon contrasts starkly with
      "stress cross-protection," where exposure to one stress protects against
      subsequent exposure to a different stress. Previously we demonstrated that the
      pathogenCandida albicansis acutely sensitive to combinations of cationic and
      oxidative stresses, because the induction of H2O2-responsive genes is blocked in
      the presence of cationic stress. We reveal that this is due to novel mechanisms
      that delay activation of the Cap1 AP-1-like transcription factor, the major
      regulator of the H2O2-induced regulon. Cap1 becomes trapped in a partially
      oxidized form following simultaneous exposure to oxidative and cationic stresses.
      In addition, cationic stress promotes the interaction of Cap1 with the Crm1
      nuclear export factor, thus inhibiting its nuclear accumulation. These mechanisms
      probably explain the potency of neutrophils, which employ multiple stresses to
      kill fungal pathogens.

PMID- 27025255
TI  - Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling
      pathway and exhibits a dual function.
AB  - Rheumatoid arthritis (RA) is the most common form of chronic inflammatory
      rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major
      interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in
      early RA but its pathophysiologic role remains unknown. The main objective of
      this study was to investigate the in vitro effects of soluble ENO1 on peripheral
      blood mononuclear cells (PBMC) from healthy donors and RA patients in order to
      determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis,
      experiments of receptor inhibition and flow cytometry analysis were performed to
      determine the effect, the target cell population and the receptor of ENO1. We
      showed that ENO1 has the ability to induce early production of pro-inflammatory
      cytokines and chemokines with delayed production of IL-10 and to activate the
      innate immune system. We demonstrated that ENO1 binds mainly to monocytes and
      activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA
      patients. Our results establish for the first time that ENO1 is able to activate
      in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism
      firstly pro-inflammatory and secondly anti-inflammatory. These results contribute
      to elucidating the role of this auto-antigen in the pathophysiologic mechanisms
      of RA. 

PMID- 27025257
TI  - Oxygen Vacancy Induced Room-Temperature Metal-Insulator Transition in Nickelate
      Films and Its Potential Application in Photovoltaics.
AB  - Oxygen vacancy is intrinsically coupled with magnetic, electronic, and transport
      properties of transition-metal oxide materials and directly determines their
      multifunctionality. Here, we demonstrate reversible control of oxygen content by
      postannealing at temperature lower than 300  degrees C and realize the reversible
      metal-insulator transition in epitaxial NdNiO3 films. Importantly, over 6 orders
      of magnitude in the resistance modulation and a large change in optical bandgap
      are demonstrated at room temperature without destroying the parent framework and
      changing the p-type conductive mechanism. Further study revealed that oxygen
      vacancies stabilized the insulating phase at room temperature is universal for
      perovskite nickelate films. Acting as electron donors, oxygen vacancies not only
      stabilize the insulating phase at room temperature, but also induce a large
      magnetization of ~50 emu/cm3 due to the formation of strongly correlated Ni2+
      t(2g)6e(g)2 states. The bandgap opening is an order of magnitude larger than that
      of the thermally driven metal-insulator transition and continuously tunable.
      Potential application of the newly found insulating phase in photovoltaics has
      been demonstrated in the nickelate-based heterojunctions. Our discovery opens up
      new possibilities for strongly correlated perovskite nickelates.

PMID- 27025256
TI  - Essential role of the Cdk2 activator RingoA in meiotic telomere tethering to the
      nuclear envelope.
AB  - Cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation. Genetic
      analysis in mice has revealed an essential role for Cdk2 in meiosis, which
      renders Cdk2 knockout (KO) mice sterile. Here we show that mice deficient in
      RingoA, an atypical activator of Cdk1 and Cdk2 that has no amino acid sequence
      homology to cyclins, are sterile and display meiotic defects virtually identical
      to those observed in Cdk2 KO mice including non-homologous chromosome pairing,
      unrepaired double-strand breaks, undetectable sex-body and pachytene arrest.
      Interestingly, RingoA is required for Cdk2 targeting to telomeres and RingoA KO
      spermatocytes display severely affected telomere tethering as well as impaired
      distribution of Sun1, a protein essential for the attachment of telomeres to the
      nuclear envelope. Our results identify RingoA as an important activator of Cdk2
      at meiotic telomeres, and provide genetic evidence for a physiological function
      of mammalian Cdk2 that is not dependent on cyclins. 

PMID- 27025258
TI  - microRNA-146a promotes mycobacterial survival in macrophages through suppressing
      nitric oxide production.
AB  - Macrophages play a crucial role in host innate anti-mycobacterial defense, which
      is tightly regulated by multiple factors, including microRNAs. Our previous study
      showed that a panel of microRNAs was markedly up-regulated in macrophages upon
      mycobacterial infection. Here, we investigated the biological function of miR
      146a during mycobacterial infection. miR-146a expression was induced both in
      vitro and in vivo after Mycobacterium bovis BCG infection. The inducible miR-146a
      could suppress the inducible nitric oxide (NO) synthase (iNOS) expression and NO
      generation, thus promoting mycobacterial survival in macrophages. Inhibition of
      endogenous miR-146a increased NO production and mycobacterial clearance.
      Moreover, miR-146a attenuated the activation of nuclear factor kappaB and mitogen
      activated protein kinases signaling pathways during BCG infection, which in turn
      repressed iNOS expression. Mechanistically, miR-146a directly targeted tumor
      necrosis factor (TNF) receptor-associated factor 6 (TRAF6) at post
      transcriptional level. Silencing TRAF6 decreased iNOS expression and NO
      production in BCG-infected macrophages, while overexpression of TRAF6 reversed
      miR-146a-mediated inhibition of NO production and clearance of mycobacteria.
      Therefore, we demonstrated a novel role of miR-146a in the modulation of host
      defense against mycobacterial infection by repressing NO production via targeting
      TRAF6, which may provide a promising therapeutic target for tuberculosis. 

PMID- 27025260
TI  - Real-time-guided bone regeneration around standardized critical size calvarial
      defects using bone marrow-derived mesenchymal stem cells and collagen membrane
      with and without using tricalcium phosphate: an in vivo micro-computed
      tomographic and histologic experiment in rats.
AB  - The aim of the present real time in vivo micro-computed tomography (uCT) and
      histologic experiment was to assess the efficacy of guided bone regeneration
      (GBR) around standardized calvarial critical size defects (CSD) using bone marrow
      derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and
      without tricalcium phosphate (TCP) graft material. In the calvaria of nine female
      Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under
      general anesthesia. Treatment-wise, rats were divided into three groups. In group
      1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and
      covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and
      covered with CM. All defects were closed using resorbable sutures. Bone volume
      and bone mineral density of newly formed bone (NFB) and remaining TCP particles
      and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks
      using in vivo uCT. At the 10th week, the rats were killed and calvarial segments
      were assessed histologically. The results showed that the hardness of NFB was
      similar to that of the native bone in groups 1 and 2 as compared to the NFB in
      group 3. Likewise, values for the modulus of elasticity were also significantly
      higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in
      combination with BMSCs and without CM was unable to form bone of significant
      strength that could possibly provide mechanical "lock" between the natural bone
      and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone
      formation as early as 2 weeks of treatment compared to when GBR is attempted
      without adjunct BMSC therapy. 

PMID- 27025259
TI  - New strategies against drug resistance to herpes simplex virus.
AB  - Herpes simplex virus (HSV), a member of the Herpesviridae family, is a
      significant human pathogen that results in mucocutaneous lesions in the oral
      cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues
      can successfully treat HSV infections, but the emergence of drug resistance to
      ACV has created a barrier for the treatment of HSV infections, especially in
      immunocompromised patients. There is an urgent need to explore new and effective
      tactics to circumvent drug resistance to HSV. This review summarises the current
      strategies in the development of new targets (the DNA helicase/primase (H/P)
      complex), new types of molecules (nature products) and new antiviral mechanisms
      (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of
      HSV. 

PMID- 27025261
TI  - The effect of basic fibroblast growth factor on regeneration in a surgical wound
      model of rat submandibular glands.
AB  - This study developed an animal model of surgically wounded submandibular glands
      (SMGs) and investigated the effects of collagen gel with basic fibroblast growth
      factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The
      animal model was produced by creating a surgical wound using a 3-mm diameter
      biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF
      group) or without bFGF (control group). In the animal model of surgically wounded
      SMGs, salivary glands without scar tissue around the wound area were observed
      with smaller areas of collagen gel. Small round and spindle-shape cells invaded
      the collagen gel in both groups after operation day (AOD) 5, and this invasion
      dramatically increased at AOD 7. Host tissue completely replaced the collagen gel
      at AOD 21. The invading immune cells in the group treated with collagen gel with
      bFGF were positive for vimentin, alpha-smooth muscle actin (alphaSMA), CD49f, c
      kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, alphaSMA,
      CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of
      collagen gels with bFGF improves salivary gland regeneration. 

PMID- 27025262
TI  - Modification of tooth development by heat shock protein 60.
AB  - Although several heat shock proteins have been investigated in relation to tooth
      development, no available information is available about the spatial and temporal
      expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60
      expression in the structures of the developing tooth germ, we used Western
      blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in
      high amounts in the inner and outer enamel epithelia, enamel knot (EK) and
      stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the
      bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower
      incisors from mice, we performed in vitro culturing. To investigate the effect of
      exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2
      deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered
      Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but
      it did not influence the proliferation rate of dental cells. We identified the
      expression of Hsp 60 in the developing tooth germ, which was present in high
      concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts.
      High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth
      germ, but it did not influence the proliferation rate of the dental cells. Our
      results suggest that increased levels of Hsp 60 may cause abnormalities in the
      morphological development of the tooth germ and support the data on the
      significance of Hsp during the developmental processes. 

PMID- 27025263
TI  - Loss of Abeta-nerve endings associated with the Merkel cell-neurite complex in
      the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.
AB  - The Merkel cell-neurite complex initiates the perception of touch and mediates
      Abeta slowly adapting type I responses. Lichen planus is a chronic inflammatory
      autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is
      characterized with or without epithelial dysplasia in the oral mucosa. To
      determine the effects of lichen planus and hyperkeratosis on the Merkel cell
      neurite complex, healthy oral mucosal epithelium and lesional oral mucosal
      epithelium of lichen planus and hyperkeratosis patients were stained by
      immunohistochemistry (the avidin-biotin-peroxidase complex and double
      immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel
      cell marker), and neurofilament 200 (NF200, a myelinated Abeta- and Adelta-nerve
      fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy
      tissues and in the lesional oral mucosa epithelium of lichen planus and
      hyperkeratosis were counted and statistically analysed. In the healthy oral
      mucosa, K20-positive Merkel cells with and without close association to the
      intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa
      of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve
      fibres were detected only in the lamina propria. Compared with healthy tissues,
      lichen planus and hyperkeratosis tissues had significantly decreased numbers of
      NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and
      hyperkeratosis were associated with the absence of Abeta-nerve endings in the
      oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the
      Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen
      planus and hyperkeratosis. 

PMID- 27025264
TI  - Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic
      mandibular growth.
AB  - The goal of this study was to assess the effect of the intermittent combination
      of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on
      treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular
      bone formation and growth. Forty 3-week-old male Wistar rats were divided into
      four groups: the control group (normal rats), the control C+D group (normal rats
      injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats
      injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled
      diabetic rats). An experimental DM condition was induced in the male Wistar rats
      in the diabetic and diabetic C+D groups using a single dose of 60 mg.kg(-1) body
      weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected
      in the rats of the control C+D and diabetic C+D groups. All rats were killed
      after 4 weeks, and the right mandibles were evaluated by micro-computed
      tomography and histomorphometric analysis. Diabetic rats showed a significant
      deterioration in bone quality and bone formation (diabetic group). By contrast,
      with the injection of calcitonin and vitamin D3, both bone parameters and bone
      formation significantly improved (diabetic C+D group) (P < 0.05). These findings
      suggest that these two hormones might potentially improve various bone
      properties. 

PMID- 27025265
TI  - Effects of quaternary ammonium chain length on the antibacterial and
      remineralizing effects of a calcium phosphate nanocomposite.
AB  - Composites containing nanoparticles of amorphous calcium phosphate (NACP)
      remineralize tooth lesions and inhibit caries. A recent study synthesized
      quaternary ammonium methacrylates (QAMs) with chain lengths (CLs) of 3-18 and
      determined their effects on a bonding agent. This study aimed to incorporate
      these QAMs into NACP nanocomposites for the first time to simultaneously endow
      the material with antibacterial and remineralizing capabilities and to
      investigate the effects of the CL on the mechanical and biofilm properties. Five
      QAMs were synthesized: DMAPM (CL3), DMAHM (CL6), DMADDM (CL12), DMAHDM (CL16),
      and DMAODM (CL18). Each QAM was incorporated into a composite containing 20% NACP
      and 50% glass fillers. A dental plaque microcosm biofilm model was used to
      evaluate the antibacterial activity. The flexural strength and elastic modulus of
      nanocomposites with QAMs matched those of a commercial control composite (n = 6;
      P > 0.1). Increasing the CL from 3 to 16 greatly enhanced the antibacterial
      activity of the NACP nanocomposite (P < 0.05); further increasing the CL to 18
      decreased the antibacterial potency. The NACP nanocomposite with a CL of 16
      exhibited biofilm metabolic activity and acid production that were 10-fold lesser
      than those of the control composite. The NACP nanocomposite with a CL of 16
      produced 2-log decreases in the colony-forming units (CFU) of total
      microorganisms, total streptococci, and mutans streptococci. In conclusion, QAMs
      with CLs of 3-18 were synthesized and incorporated into an NACP nanocomposite for
      the first time to simultaneously endow the material with antibacterial and
      remineralization capabilities. Increasing the CL reduced the metabolic activity
      and acid production of biofilms and caused a 2-log decrease in CFU without
      compromising the mechanical properties. Nanocomposites exhibiting strong anti
      biofilm activity, remineralization effects, and mechanical properties are
      promising materials for tooth restorations that inhibit caries. 

PMID- 27025266
TI  - A simple, sensitive and non-destructive technique for characterizing bovine
      dental enamel erosion: attenuated total reflection Fourier transform infrared
      spectroscopy.
AB  - Although many techniques are available to assess enamel erosion in vitro, a
      simple, non-destructive method with sufficient sensitivity for quantifying dental
      erosion is required. This study characterized the bovine dental enamel erosion
      induced by various acidic beverages in vitro using attenuated total reflection
      Fourier transform infrared (ATR-FTIR) spectroscopy. Deionized water (control) and
      10 acidic beverages were selected to study erosion, and the pH and neutralizable
      acidity were measured. Bovine anterior teeth (110) were polished with up to 1 200
      grit silicon carbide paper to produce flat enamel surfaces, which were then
      immersed in 20 mL of the beverages for 30 min at 37  degrees C. The degree of
      erosion was evaluated using ATR-FTIR spectroscopy and Vickers' microhardness
      measurements. The spectra obtained were interpreted in two ways that focused on
      the nu1, nu3 phosphate contour: the ratio of the height amplitude of nu3 PO4 to
      that of nu1 PO4 (Method 1) and the shift of the nu3 PO4 peak to a higher
      wavenumber (Method 2). The percentage changes in microhardness after the erosion
      treatments were primarily affected by the pH of the immersion media. Regression
      analyses revealed highly significant correlations between the surface hardness
      change and the degree of erosion, as detected by ATR-FTIR spectroscopy (P<0.001).
      Method 1 was the most sensitive to these changes, followed by surface hardness
      change measurements and Method 2. This study suggests that ATR-FTIR spectroscopy
      is potentially advantageous over the microhardness test as a simple, non
      destructive, sensitive technique for the quantification of enamel erosion. 

PMID- 27025267
TI  - Short-term effects of repetitive transcranial magnetic stimulation on sleep
      bruxism - a pilot study.
AB  - The purpose of this study was to investigate the effects of repetitive
      transcranial magnetic stimulation (rTMS) on patients with sleep bruxism (SB).
      Twelve patients with SB were included in an open, single-intervention pilot
      study. rTMS at 1 Hz and an intensity of 80% of the active motor threshold was
      applied to the 'hot spot' of the masseter muscle representation at the primary
      motor cortex bilaterally for 20 min per side each day for 5 consecutive days. The
      jaw-closing muscle electromyographic (EMG) activity during sleep was recorded
      with a portable EMG recorder at baseline, during rTMS treatment and at follow-up
      for 5 days. In addition, patients scored their jaw-closing muscle soreness on a 0
      10 numerical rating scale (NRS). Data were analysed with analysis of variance.
      The intensity of the EMG activity was suppressed during and after rTMS compared
      to the baseline (P = 0.04; P = 0.02, respectively). The NRS score of soreness
      decreased significantly during and after rTMS compared with baseline (P < 0.01).
      These findings indicated a significant inhibition of jaw-closing muscle activity
      during sleep along with a decrease of muscle soreness. This pilot study raises
      the possibility of therapeutic benefits from rTMS in patients with bruxism and
      calls for further and more controlled studies. 

PMID- 27025269
TI  - Optical and magneto-optical behavior of Cerium Yttrium Iron Garnet thin films at
      wavelengths of 200-1770 nm.
AB  - Magneto-optical cerium-substituted yttrium iron garnet (Ce:YIG) thin films
      display Faraday and Kerr rotation (rotation of light polarisation upon
      transmission and reflection, respectively) as well as a nonreciprocal phase shift
      due to their non-zero off-diagonal permittivity tensor elements, and also possess
      low optical absorption in the near-infrared. These properties make Ce:YIG useful
      in providing nonreciprocal light propagation in integrated photonic circuits,
      which is essential for accomplishing energy-efficient photonic computation and
      data transport architectures. In this study, 80 nm-thick Ce:YIG films were grown
      on Gadolinium Gallium Garnet substrates with (100), (110) and (111) orientations
      using pulsed laser deposition. The films had bulk-like structural and magnetic
      quality. Faraday and Kerr spectroscopies along with spectroscopic ellipsometry
      were used to deduce the complete permittivity tensor of the films in the
      ultraviolet, visible and near-infrared spectral region, and the magneto-optical
      figure of merit as a function of wavelength was determined. The samples showed
      the highest IR Faraday rotation reported for thin films of Ce:YIG, which
      indicates the importance of this material in development of nonreciprocal
      photonic devices.

PMID- 27025268
TI  - Diagnostic value of alcoholic liver disease (ALD)/nonalcoholic fatty liver
      disease (NAFLD) index combined with gamma-glutamyl transferase in differentiating
      ALD and NAFLD.
AB  - BACKGROUND/AIMS: This study aimed to verify the reliability of the alcoholic
      liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index (ANI) for
      distinguishing ALD in patients with hepatic steatosis from NAFLD, and to
      investigate whether ANI combined with gamma-glutamyl transferase (GGT) would
      enhance the accuracy of diagnosis in China. METHODS: A hundred thirty-nine cases
      of fatty liver disease (FLD) were divided into two groups of ALD and NAFLD. The
      ANI was calculated with an online calculator. All indicators and ANI values were
      analyzed using statistical methods. RESULTS: ANI was significantly higher in
      patients with ALD than in those with NAFLD (7.11 +/- 5.77 vs. -3.09 +/- 3.89, p <
      0.001). With a cut-off value of -0.22, the sensitivity, specificity, and area
      under the receiver operating characteristic curve (AUROC) of diagnosed ALD cases
      was 87.1%, 92.5%, and 0.934 (95% confidence interval [CI], 0.879 to 0.969),
      respectively. The corresponding values for aspartate aminotransferase
      (AST)/alanine transaminase (ALT), mean corpuscular volume (MCV), and GGT were
      75.29%, 72.94%, and 0.826 (95% CI, 0.752 to 0.885); 94.34%, 83.02%, and 0.814
      (95% CI, 0.739 to 0.875) and 80.23%, 79.25%, and 0.815 (95% CI, 0.740 to 0.876),
      respectively. ANI AUROC was significantly higher than the AST/ALT, MCV, or GGT
      AUROCs (all p < 0.001), moreover, ANI showed better diagnostic performance. The
      combination of ANI and GGT showed a better AUROC than ANI alone (0.976 vs. 0.934,
      p = 0.016). The difference in AUROCs between AST/ALT, MCV, and GGT was not
      statistically significant (all p > 0.05). CONCLUSIONS: ANI can help distinguish
      ALD from NAFLD with high accuracy; when ANI was combined with GGT, its
      effectiveness improved further.

PMID- 27025270
TI  - A decade of pig genome sequencing: a window on pig domestication and evolution.
AB  - Insight into how genomes change and adapt due to selection addresses key
      questions in evolutionary biology and in domestication of animals and plants by
      humans. In that regard, the pig and its close relatives found in Africa and
      Eurasia represent an excellent group of species that enables studies of the
      effect of both natural and human-mediated selection on the genome. The recent
      completion of the draft genome sequence of a domestic pig and the development of
      next-generation sequencing technology during the past decade have created
      unprecedented possibilities to address these questions in great detail. In this
      paper, I review recent whole-genome sequencing studies in the pig and closely
      related species that provide insight into the demography, admixture and selection
      of these species and, in particular, how domestication and subsequent selection
      of Sus scrofa have shaped the genomes of these animals. 

PMID- 27025271
TI  - Utilizing yeast chemogenomic profiles for the prediction of pharmacogenomic
      associations in humans.
AB  - Understanding the genetic basis underlying individual responses to drug treatment
      is a fundamental task with implications to drug development and administration.
      Pharmacogenomics is the study of the genes that affect drug response. The study
      of pharmacogenomic associations between a drug and a gene that influences the
      interindividual drug response, which is only beginning, holds much promise and
      potential. Although relatively few pharmacogenomic associations between drugs and
      specific genes were mapped in humans, large systematic screens have been carried
      out in the yeast Saccharomyces cerevisiae, motivating the constructing of a
      projection method. We devised a novel approach for the prediction of
      pharmacogenomic associations in humans using genome-scale chemogenomic data from
      yeast. We validated our method using both cross-validation and comparison to
      known drug-gene associations extracted from multiple data sources, attaining high
      AUC scores. We show that our method outperforms a previous technique, as well as
      a similar method based on known human associations. Last, we analyze the
      predictions and demonstrate their biological relevance to understanding drug
      response. 

PMID- 27025272
TI  - Platelet bound oxLDL shows an inverse correlation with plasma anaphylatoxin C5a
      in patients with coronary artery disease.
AB  - Both oxidized lipids as well as the complement system contribute to
      atherothrombosis. The expression of complement receptors correlates with the
      expression of platelet activation markers, and platelet bound oxidized low
      density lipoprotein (oxLDL) modulates platelet function. In the present study, we
      investigated the relationship of markers of complement activation, the
      anaphylatoxins C5a and C3a, and oxidized low-density lipoprotein. Two hundred and
      seven patients with coronary artery disease (CAD) were analyzed in this study.
      Using enzyme-linked immunosorbent assays, plasma levels of oxLDL, C3a, and C5a
      were measured. Moreover, we assessed platelet bound oxLDL by flow cytometry. The
      overall level of C5a in the troponin negative group (stable angina (SA) and
      unstable angina (UA)) compared to the troponin positive group (non-ST-elevation
      myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI))
      did not differ significantly (62.7 +/- 32.4 ng/ml versus 65.8 +/- 40.3 ng/ml).
      While C5a and C3a showed a significant correlation with each other (r = 0.25, p <
      0.001), there was no statistically significant relationship between C3a and
      platelet bound oxLDL (r = 0.06, p = 0.37). Furthermore, plasma oxLDL did not
      correlate with either C3a or C5a. However, we observed a moderate, yet
      significant negative correlation between plasma C5a and platelet bound oxLDL (r =
      -0.15, p = 0.04). Partial correlation analysis correcting for the presence of
      acute coronary syndrome (ACS), troponin status or the subgroups SA, UA, NSTEMI,
      or STEMI did not alter this correlation substantially. Interestingly, flow
      cytometric analysis of human platelets showed increased expression of C5aR and P
      selectin after in vitro stimulation with oxLDL. In conclusion, the complement
      anaphylatoxin C5a shows an inverse correlation with platelet bound oxLDL. The
      relationship of oxidized lipids to particular complement components may add to
      the platelet-lipid interplay in atherogenesis and trigger future clinical and
      mechanistic studies.

PMID- 27025273
TI  - The formation of catalytically competent enzyme-substrate complex is not a
      bottleneck in lesion excision by human alkyladenine DNA glycosylase.
AB  - Human alkyladenine DNA glycosylase (AAG) protects DNA from alkylated and
      deaminated purine lesions. AAG flips out the damaged nucleotide from the double
      helix of DNA and catalyzes the hydrolysis of the N-glycosidic bond to release the
      damaged base. To understand better, how the step of nucleotide eversion
      influences the overall catalytic process, we performed a pre-steady-state kinetic
      analysis of AAG interaction with specific DNA-substrates, 13-base pair duplexes
      containing in the 7th position 1-N6-ethenoadenine (epsilonA), hypoxanthine (Hx),
      and the stable product analogue tetrahydrofuran (F). The combination of the
      fluorescence of tryptophan, 2-aminopurine, and 1-N6-ethenoadenine was used to
      record conformational changes of the enzyme and DNA during the processes of DNA
      lesion recognition, damaged base eversion, excision of the N-glycosidic bond, and
      product release. The thermal stability of the duplexes characterized by the
      temperature of melting, Tm, and the rates of spontaneous opening of individual
      nucleotide base pairs were determined by NMR spectroscopy. The data show that the
      relative thermal stability of duplexes containing a particular base pair in
      position 7, (Tm(F/T) < Tm(epsilonA/T) < Tm(Hx/T) < Tm(A/T)) correlates with the
      rate of reversible spontaneous opening of the base pair. However, in contrast to
      that, the catalytic lesion excision rate is two orders of magnitude higher for Hx
      containing substrates than for substrates containing epsilonA, proving that
      catalytic activity is not correlated with the stability of the damaged base pair.
      Our study reveals that the formation of the catalytically competent enzyme
      substrate complex is not the bottleneck controlling the catalytic activity of
      AAG.

PMID- 27025274
TI  - A simple strategy to the side chain functionalization on the quinoxaline unit for
      efficient polymer solar cells.
AB  - A new tetrafluoridequinoxaline electron accepting block from a quinoxaline core,
      which is substituted with a fluorine atom onto its backbone and side chains, was
      designed. A new copolymer (PBDTT-ffQx) was synthesized from
      tetrafluoridequinoxaline and benzodithiophene. The copolymer was characterized in
      detail. The photovoltaic properties were well investigated. A high PCE of 8.6%
      based on the single junction device was obtained. 

PMID- 27025275
TI  - Influence of graded inclusion of white lupin (Lupinus albus) meal on performance,
      nutrient digestibility and intestinal morphology of broiler chickens.
AB  - The aim of this study was to investigate the effect of white lupin (Lupinus
      albus) meal (WLM) addition on the intestinal viscosity, bird performance,
      nutrient utilisation and villi morphology of growing broiler chicks. The
      experiment was conducted with 480 broiler chicks divided into 6 dietary
      treatments, including a maize-soybean meal control diet (CON) and 5 experimental
      diets containing 100, 150, 200, 250 and 300 g/kg WLM. During the period from d 0
      to 35, birds fed on 200 or higher WLM/kg were characterised by lower body weight
      gain and feed intake than CON. The use of 150 g of WLM/kg increased feed
      conversion ratio (FCR) compared to CON treatment. Apparent metabolisable energy
      corrected to zero N balance (AMEN) and apparent ileal digestibility of dry
      matter, ether extract, crude protein and starch, linearly decreased as WLM
      increased from 0 to 300 g/kg. There was a quadratic effect of WLM dose on sialic
      acid excretion. A strong negative linear correlation was found between the
      excretion of sialic acid and AMEN. The viscosity of ileal digesta was linearly
      increased as WLM increased. The effect of WLM dose on ileum villus height (VH)
      was linear, while that on ileum villus area (VA) was quadratic. Both parameters
      decreased as WLM increased from 0 to 300 g/kg. In conclusion, the use of over 150
      g/kg of WLM in broiler diets depressed performance results. However, depression
      of nutrient utilisation was only observed when 250 or 300 g/kg of WLM was used. 

PMID- 27025276
TI  - Self-organizing p-quinquephenyl building blocks incorporating lateral hydroxyl
      and methoxyl groups into supramolecular nano-assemblies.
AB  - The self-assembling behavior of coil-rod-coil molecules 1a, 1b, and 2a, 2b was
      investigated using DSC, POM, SAXS, and AFM in bulk and aqueous solutions. These
      molecules contain p-quinquephenyl groups as rod segments incorporating lateral
      hydroxyl or methoxyl groups in the center positions and oligo(ethylene oxide)s as
      the coil segments. Molecules 1a and 1b, with lateral methoxyl groups in the rod
      segments, self-assemble into oblique columnar structures in the crystalline phase
      and transform into nematic phases. On the other hand, molecules 2a and 2b, with
      hydroxyl groups in the center of their rod segments, self-organize into hexagonal
      perforated lamellar and oblique columnar nano-structures in the crystalline and
      liquid crystalline phase, respectively. In aqueous solutions, these molecules
      aggregate into nano-ribbons and vesicles, depending on their lateral groups and
      oligo(ethylene oxide) chain lengths. These results imply that the lateral
      methoxyl or hydroxyl groups, present in the center of the rod segments,
      significantly influence the formation of various supramolecular nano-structures
      in the bulk state and in aqueous solution. This is achieved via tuning of the non
      covalent interactions of the rod building blocks.

PMID- 27025277
TI  - Sub-10 nm feature chromium photomasks for contact lithography patterning of
      square metal ring arrays.
AB  - Advances in photolithographic processes have allowed semiconductor industries to
      manufacture smaller and denser chips. As the feature size of integrated circuits
      becomes smaller, there has been a growing need for a photomask embedded with ever
      narrower patterns. However, it is challenging for electron beam lithography to
      obtain <10 nm linewidths with wafer scale uniformity and a necessary speed. Here,
      we introduce a photolithography-based, cost-effective mask fabrication method
      based on atomic layer deposition and overhang structures for sacrificial layers.
      Using this method, we obtained sub-10 nm square ring arrays of side length 50
      MUm, and periodicity 100 MUm on chromium film, on 1 cm by 1 cm quartz substrate.
      These patterns were then used as a contact-lithography photomask using 365 nm I
      line, to generate metal ring arrays on silicon substrate.

PMID- 27025278
TI  - A 3D printed microfluidic device for production of functionalized hydrogel
      microcapsules for culture and differentiation of human Neuronal Stem Cells
      (hNSC).
AB  - We present here a microfluidic device that generates sub-millimetric hollow
      hydrogel spheres, encapsulating cells and coated internally with a layer of
      reconstituted extracellular matrix (ECM) of a few microns thick. The spherical
      capsules, composed of alginate hydrogel, originate from the spontaneous
      instability of a multi-layered jet formed by co-extrusion using a coaxial flow
      device. We provide a simple design to manufacture this device using a DLP
      (digital light processing) 3D printer. Then, we demonstrate how the inner wall of
      the capsules can be decorated with a continuous ECM layer that is anchored to the
      alginate gel and mimics the basal membrane of a cellular niche. Finally, we used
      this approach to encapsulate human Neural Stem Cells (hNSC) derived from human
      Induced Pluripotent Stem Cells (hIPSC), which were further differentiated into
      neurons within the capsules with negligible loss of viability. Altogether, we
      show that these capsules may serve as cell micro-containers compatible with
      complex cell culture conditions and applications. These developments widen the
      field of research and biomedical applications of the cell encapsulation
      technology.

PMID- 27025279
TI  - Participatory Research as One Piece of the Puzzle: A Systematic Review of
      Consumer Involvement in Design of Technology-Based Youth Mental Health and Well
      Being Interventions.
AB  - BACKGROUND: Despite the potential of technology-based mental health interventions
      for young people, limited uptake and/or adherence is a significant challenge. It
      is thought that involving young people in the development and delivery of
      services designed for them leads to better engagement. Further research is
      required to understand the role of participatory approaches in design of
      technology-based mental health and well-being interventions for youth. OBJECTIVE:
      To investigate consumer involvement processes and associated outcomes from
      studies using participatory methods in development of technology-based mental
      health and well-being interventions for youth. METHODS: Fifteen electronic
      databases, using both resource-specific subject headings and text words, were
      searched describing 2 broad concepts-participatory research and mental
      health/illness. Grey literature was accessed via Google Advanced search, and
      relevant conference Web sites and reference lists were also searched. A first
      screening of titles/abstracts eliminated irrelevant citations and documents. The
      remaining citations were screened by a second reviewer. Full text articles were
      double screened. All projects employing participatory research processes in
      development and/or design of (ICT/digital) technology-based youth mental health
      and well-being interventions were included. No date restrictions were applied;
      English language only. Data on consumer involvement, research and design process,
      and outcomes were extracted via framework analysis. RESULTS: A total of 6210
      studies were reviewed, 38 full articles retrieved, and 17 included in this study.
      It was found that consumer participation was predominantly consultative and
      consumerist in nature and involved design specification and intervention
      development, and usability/pilot testing. Sustainable participation was difficult
      to achieve. Projects reported clear dichotomies around designer/researcher and
      consumer assumptions of effective and acceptable interventions. It was not
      possible to determine the impact of participatory research on intervention
      effectiveness due to lack of outcome data. Planning for or having pre-existing
      implementation sites assisted implementation. The review also revealed a lack of
      theory-based design and process evaluation. CONCLUSIONS: Consumer consultations
      helped shape intervention design. However, with little evidence of outcomes and a
      lack of implementation following piloting, the value of participatory research
      remains unclear.

PMID- 27025287
TI  - Mobile Phone-Based Unobtrusive Ecological Momentary Assessment of Day-to-Day
      Mood: An Explorative Study.
AB  - BACKGROUND: Ecological momentary assessment (EMA) is a useful method to tap the
      dynamics of psychological and behavioral phenomena in real-world contexts.
      However, the response burden of (self-report) EMA limits its clinical utility.
      OBJECTIVE: The aim was to explore mobile phone-based unobtrusive EMA, in which
      mobile phone usage logs are considered as proxy measures of clinically relevant
      user states and contexts. METHODS: This was an uncontrolled explorative pilot
      study. Our study consisted of 6 weeks of EMA/unobtrusive EMA data collection in a
      Dutch student population (N=33), followed by a regression modeling analysis.
      Participants self-monitored their mood on their mobile phone (EMA) with a one
      dimensional mood measure (1 to 10) and a two-dimensional circumplex measure
      (arousal/valence, -2 to 2). Meanwhile, with participants' consent, a mobile phone
      app unobtrusively collected (meta) data from six smartphone sensor logs
      (unobtrusive EMA: calls/short message service (SMS) text messages, screen time,
      application usage, accelerometer, and phone camera events). Through forward
      stepwise regression (FSR), we built personalized regression models from the
      unobtrusive EMA variables to predict day-to-day variation in EMA mood ratings.
      The predictive performance of these models (ie, cross-validated mean squared
      error and percentage of correct predictions) was compared to naive benchmark
      regression models (the mean model and a lag-2 history model). RESULTS: A total of
      27 participants (81%) provided a mean 35.5 days (SD 3.8) of valid EMA/unobtrusive
      EMA data. The FSR models accurately predicted 55% to 76% of EMA mood scores.
      However, the predictive performance of these models was significantly inferior to
      that of naive benchmark models. CONCLUSIONS: Mobile phone-based unobtrusive EMA
      is a technically feasible and potentially powerful EMA variant. The method is
      young and positive findings may not replicate. At present, we do not recommend
      the application of FSR-based mood prediction in real-world clinical settings.
      Further psychometric studies and more advanced data mining techniques are needed
      to unlock unobtrusive EMA's true potential.

PMID- 27025288
TI  - Late surgical complications of subtotal colectomy with antiperistaltic caeco
      rectal anastomosis for slow transit constipation A critical analysis.
AB  - PURPOSE: Despite a good percentage of success, mainly related to the amelioration
      of patient selection, surgery for slow transit constipation still presents
      failures and late complications, often unpredictable, and sometimes related to
      technical variants. The aim of the study is to critically analyze late surgical
      complications of subtotal colectomy with caeco-rectal anastomosis (SCCRA),
      examining the peculiar risks of the procedure and possible prevention measures.
      METHODS: Follow-up data of 43 compliant patients submitted to SCCRA at our
      Institution were reviewed. Patients undergoing further surgery for a complication
      clearly related to SCCRA at our centre were included. RESULTS: We identified
      three late surgical complications (7%): a caecal distension, an ileo-caecal
      volvulus and an ileal volvulus. all patients were successfully treated. an
      evident predisposing condition was found only in the first case. CONCLUSIONS:
      Peculiar long term complications related to the presence of a dysfunctional or
      mobile caecal stump may be prevented by careful patient selection and surgical
      technique. KEY WORDS: Constipation, Complication, Caecal distension, Ileo-caecal
      volvulus, Subtotal colectomy.

PMID- 27025289
TI  - Medical versus surgical treatment for refractory or recurrent peptic ulcer.
AB  - BACKGROUND: Refractory peptic ulcers are ulcers in the stomach or duodenum that
      do not heal after eight to 12 weeks of medical treatment or those that are
      associated with complications despite medical treatment. Recurrent peptic ulcers
      are peptic ulcers that recur after healing of the ulcer. Given the number of
      deaths due to peptic ulcer-related complications and the long-term complications
      of medical treatment (increased incidence of fracture), it is unclear whether
      medical or surgical intervention is the better treatment option in people with
      recurrent or refractory peptic ulcers. OBJECTIVES: To assess the benefits and
      harms of medical versus surgical treatment for people with recurrent or
      refractory peptic ulcer. SEARCH METHODS: We searched the specialised register of
      the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central
      Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE,
      Science Citation Index Expanded, and trials registers until September 2015 to
      identify randomised trials and non-randomised studies, using search strategies.
      We also searched the references of included studies to identify further studies.
      SELECTION CRITERIA: We considered randomised controlled trials and non-randomised
      studies comparing medical treatment with surgical treatment in people with
      refractory or recurrent peptic ulcer, irrespective of language, blinding, or
      publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two
      review authors independently identified trials and extracted data. We planned to
      calculate the risk ratio, mean difference, standardised mean difference, or
      hazard ratio with 95% confidence intervals using both fixed-effect and random
      effects models with Review Manager 5 based on intention-to-treat analysis. MAIN
      RESULTS: We included only one non-randomised study published 30 years ago in the
      review. This study included 77 participants who had gastric ulcer and in whom
      medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed
      after an average duration of treatment of 29 months. The authors do not state
      whether these were recurrent or refractory ulcers. It appears that the
      participants did not have previous complications such as bleeding or perforation.
      Of the 77 included participants, 37 participants continued to have medical
      therapy while 40 participants received surgical therapy (antrectomy with or
      without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy;
      pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy
      or excision of the ulcer; proximal gastric or parietal cell vagotomy alone;
      suture or closure of the ulcer with proximal gastric or parietal cell vagotomy).
      Whether to use medical or surgical treatment was determined by participant's or
      treating physician's preference.The study authors reported that two participants
      in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was
      identified by repeated biopsy. They did not report the proportion of participants
      who had gastric cancer in the surgical treatment group. They also did not report
      the implications of the delayed diagnosis of gastric cancer in the medical
      treatment group. They did not report any other outcomes of interest for this
      review (that is health-related quality of life (using any validated scale),
      adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer
      perforation, abdominal pain, and long-term mortality). AUTHORS' CONCLUSIONS: We
      found no studies that provide the relative benefits and harms of medical versus
      surgical treatment for recurrent or refractory peptic ulcers. Studies that
      evaluate the natural history of recurrent and refractory peptic ulcers are
      urgently required to determine whether randomised controlled trials comparing
      medical versus surgical management in patients with recurrent or refractory
      peptic ulcers or both are necessary. Such studies will also provide information
      for the design of such randomised controlled trials. A minimum follow-up of two
      to three years will allow the calculation of the incidence of complications and
      gastric cancer (in gastric ulcers only) in recurrent and refractory peptic
      ulcers. In addition to complications related to treatment and disease, health
      related quality of life and loss of productivity should also be measured.

PMID- 27025290
TI  - A case of human infection with a novel Babesia species in China.
AB  - BACKGROUND: Babesiosis is an uncommon but emerging tick-borne disease caused by
      the genus Babesia. In this case study, we report a case of human infection with a
      novel Babesia sp. in China. FINDINGS: The patient in question had been suffering
      from repetitive occurrences of mild fever of unknown origin and fatigue for 10
      years. Ring forms, tetrads, and one or two dots of chromatin or trophozoite-like
      organisms were observed in the patient's thin blood smears and bone marrow
      smears. Using a confocal laser-scanning microscope, it was observed that the
      patient's serum had reactivity with the surface proteins of the B. microti
      strain. Electron microscopy revealed oval red blood cells with 1 ~ 2 MUm of knob
      protrusions in the cellular membrane. The results of the Babesia-specific nested
      PCR assay for 18S rRNA confirmed the presence of Babesia infection. The
      construction of a phylogenetic relationship showed clustering with B. microti and
      B. duncani, which was identified as a novel Babesia species and named as Babesia
      sp. XXB/HangZhou. Azithromycin, doxycycline, and moxifloxacin hydrochloride were
      shown to relieve symptoms but were not as effective after continuous usage. After
      atovaquone (Mepron(r)) administration, the patient recovered from fever and
      tested negative for detection of Babesia-specific genes. CONCLUSION: Babesia sp.
      XXB/HangZhou is a novel Babesia species, which causes mild babesiosis in an
      immunocompetent patient.

PMID- 27025291
TI  - Go is required for the release of IL-8 and TNF-alpha, but not degranulation in
      human mast cells.
AB  - Mast cells activated by IgE-dependent and -independent mechanisms play important
      roles in innate and acquired immune responses. Activation of pertussis toxin
      (PTX)-sensitive Gi/o proteins is the key step in mast cell degranulation and
      release of de novo synthesized inflammatory mediators through IgE-independent
      mechanism. However, the roles of Gi and Go proteins in mast cells activation have
      not yet been differentiated. In the current study, the functional roles of Go
      proteins in the activities of LAD2 cells, a human mast cell line, are identified.
      Knockdown of Galphao expression significantly inhibited the synthesis of IL-8 and
      TNF-alpha from substance P activated LAD2 cells but demonstrated no effect on
      degranulation. This effect was associated with the activation of Erk and
      JNK/MAPKs signaling, whereas PI3K-Akt, calcium mobilization and NFAT
      translocation remained unchanged. These results suggest that Gi and Go proteins
      differentially regulate human mast cells activities through activating distinct
      signaling cascades. 

PMID- 27025292
TI  - Impact of polymer surface characteristics on the microrheological measurement
      quality of protein solutions - A tracer particle screening.
AB  - Microrheological measurements prove to be suitable to identify rheological
      parameters of biopharmaceutical solutions. These give information about the flow
      characteristics but also about the interactions and network structures in protein
      solutions. For the microrheological measurement tracer particles are required.
      Due to their specific surface characteristic not all are suitable for reliable
      measurement results in biopharmaceutical systems. In the present work a screening
      of melamine, PMMA, polystyrene and surface modified polystyrene as tracer
      particles were investigated at various protein solution conditions. The surface
      characteristics of the screened tracer particles were evaluated by zeta potential
      measurements. Furthermore each tracer particle was used to determine the dynamic
      viscosity of lysozyme solutions by microrheology and compared to a standard. The
      results indicate that the selection of the tracer particle had a strong impact on
      the quality of the microrheological measurement dependent on pH and additive
      type. Surface modified polystyrene was the only tracer particle that yielded good
      microrheological results for all tested conditions. The study indicated that the
      electrostatic surface charge of the tracer particle had a minor impact than its
      hydrophobicity. This characteristic was the crucial surface property that needs
      to be considered for the selection of a suitable tracer particle to achieve high
      measurement accuracy. 

PMID- 27025293
TI  - Setting accelerated dissolution test for PLGA microspheres containing peptide,
      investigation of critical parameters affecting drug release rate and mechanism.
AB  - The objective of this study was development of accelerated in vitro release
      method for peptide loaded PLGA microspheres using flow-through apparatus and
      assessment of the effect of dissolution parameters (pH, temperature, medium
      composition) on drug release rate and mechanism. Accelerated release conditions
      were set as pH 2 and 45 degrees C, in phosphate buffer saline (PBS) 0.02M. When
      the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were
      not affected, while release rate during erosion phase decreased two-fold due to
      slower ester bonds hydrolyses. Decreasing temperature from 45 degrees C to 40
      degrees C, release rate showed three-fold deceleration without significant change
      in release mechanism. Effect of medium composition on drug release was tested in
      PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer
      concentration significantly affected drug release rate and mechanism due to the
      change in osmotic pressure, while ionic strength did not have any effect on
      peptide release. Furthermore, dialysis sac and sample-and-separate techniques
      were used, in order to evaluate significance of dissolution technique choice on
      the release process. After fitting obtained data to different mathematical
      models, flow-through method was confirmed as the most appropriate for accelerated
      in vitro dissolution testing for a given formulation. 

PMID- 27025294
TI  - A comparative study of the in vitro permeation of ibuprofen in mammalian skin,
      the PAMPA model and silicone membrane.
AB  - Human skin remains the membrane of choice when conducting in vitro studies to
      determine dermal penetration of active pharmaceutical ingredients or xenobiotics.
      However there are ethical and safety issues associated with obtaining human
      tissue. For these reasons synthetic membranes, cell culture models or in silico
      predictive algorithms have been researched intensively as alternative approaches
      to predict dermal exposure in man. Porcine skin has also been recommended as an
      acceptable surrogate for topical or transdermal delivery research. Here we
      examine the in vitro permeation of a model active, ibuprofen, using human or
      porcine skin, as well as the Parallel Artificial Membrane Permeation Assay
      (PAMPA) model and silicone membrane. Finite dose studies were conducted in all
      models using commercial ibuprofen formulations and simple volatile ibuprofen
      solutions. The dose applied in the PAMPA model was also varied in order to
      determine the amount of applied formulation which best simulates typical amounts
      of topical products applied by patients or consumers. Permeation studies were
      conducted up to 6h for PAMPA and silicone and up to 48h for human and porcine
      skin. Cumulative amounts permeated at 6h were comparable for PAMPA and silicone,
      ranging from 91 to 136MUg/cm(2) across the range of formulations studied. At 48h,
      maximum ibuprofen permeation in human skin ranged from 11 to 38MUg/cm(2) and
      corresponding values in porcine skin were 59-81MUg/cm(2). A dose of 1MUL was
      confirmed as appropriate for finite dose studies in the PAMPA model. The
      formulation which delivered the greatest amount of ibuprofen in human skin was
      also significantly more efficient than other formulations when evaluated in the
      PAMPA model. The PAMPA model also discriminated between different formulation
      types (i.e. gel versus solution) compared with other models. Overall, the results
      confirm the more permeable nature of the PAMPA, silicone membrane and porcine
      tissue models to ibuprofen compared with human skin. Further finite dose studies
      to elucidate the effects of individual excipients on the barrier properties of
      the PAMPA model are needed to expand the applications of this model. The range of
      actives that are suitable for study using the model also needs to be delineated. 

PMID- 27025295
TI  - Acute generalized exanthematous pustulosis due to diltiazem: Investigation of
      cross-reactivity with other calcium channel blockers.

PMID- 27025296
TI  - Oral amoxicillin-associated anaphylaxis, 1 year after negative penicillin testing
      and oral amoxicillin challenge.

PMID- 27025297
TI  - Individualized Household Allergen Intervention Lowers Allergen Level But Not
      Asthma Medication Use: A Randomized Controlled Trial.
AB  - BACKGROUND: Environmental exposures to indoor allergens are major contributors to
      asthma symptoms, particularly in inner cities. The effectiveness of household
      allergen reduction as an adjunct to National Asthma Education Prevention Program
      guideline-based pharmacologic therapy in asthma has not been prospectively
      studied. OBJECTIVE: To study the effect of individualized allergen reduction on
      ability to reduce asthma pharmacologic therapy over 40 weeks. METHODS: We
      performed a randomized controlled trial to determine the effect of multifaceted
      indoor allergen avoidance measures on the ability to reduce asthma controller
      therapy in adults and children residing in New York City who were both sensitized
      and exposed to at least 1 indoor allergen. Asthma treatment and control were
      optimized in all subjects before randomization. RESULTS: A total of 125 subjects
      were randomized to receive individualized household allergen reduction and 122
      received a sham intervention. Subjects in the intervention group significantly
      reduced all measured allergen levels (cat, dog, dust mite allergens in the
      bedroom, cockroach and mouse allergens in the kitchen and bedroom); those in the
      control group reduced only dust mite and mouse allergens in the bedroom and
      cockroach allergen in the kitchen. Participants in the intervention arm reduced
      National Asthma Education Prevention Program-based therapy from step 4.4 at
      randomization to 3.50 postintervention (range, 0-6); participants in the control
      arm reduced medication from step 4.4 to 3.4 (P = .76). There were no differences
      in other measured asthma outcomes. CONCLUSIONS: Targeted allergen avoidance
      measures do not allow for reduction in asthma pharmacologic therapy compared with
      usual care in patients already receiving optimal controller therapy.

PMID- 27025298
TI  - Oral viscous budesonide can be successfully delivered through a variety of
      vehicles to treat eosinophilic esophagitis in children.

PMID- 27025299
TI  - Moral and social reasons to acknowledge the use of cognitive enhancers in
      competitive-selective contexts.
AB  - BACKGROUND: Although some of the most radical hypothesis related to the practical
      implementations of human enhancement have yet to become even close to reality,
      the use of cognitive enhancers is a very tangible phenomenon occurring with
      increasing popularity in university campuses as well as in other contexts. It is
      now well documented that the use of cognitive enhancers is not only increasingly
      common in Western countries, but also gradually accepted as a normal procedure by
      the media as well. In fact, its implementation is not unusual in various
      professional contexts and it has its peak in colleges (where the trend has been
      characterized as "academic doping"). Even when certain restrictions in the
      legislation of a country are indeed in place (i.e. through prescriptions
      requirements), they are without doubts easy to overcome. The legitimacy and
      appropriateness of such restrictions will not be the focus of our investigation.
      DISCUSSION: Our concern is instead related to the moral and social reasons to
      publicly acknowledge the use of cognitive enhancers in competitive-selective
      contexts. These reasons are linked to a more neutral analysis of contemporary
      Western society: it is a fact that an increasing number of competitive-selective
      contexts have a substantial number of contenders using cognitive enhancers.
      Through the use of five explicative examples, in this paper we want to analyse
      the problems related to its use. In particular, it will be our aim to show the
      tension between one of the main argument used by bio-liberals (the use of
      cognitive enhancers is an eligible procedure that society does not impose on
      anyone) and the actual implementation of the drugs in competitive, or semi
      competitive contexts.

PMID- 27025300
TI  - Perinatal arterial ischemic stroke related to carotid artery occlusion.
AB  - BACKGROUND: The aetiology of perinatal arterial ischemic stroke remains
      speculative. It is however widely accepted that the aetiology is multifactorial,
      involving various maternal, placental, foetal and neonatal risk factors. A
      resulting thromboembolic process is hypothesized and the placenta identified as
      the most plausible source. An arteriopathy, as observed in a significant
      proportion of childhood ischemic stroke, is thought to be rare. METHODS: We
      report here five cases of perinatal stroke that differ from the vast majority by
      documented carotid occlusion, and add eleven other similar cases from the
      literature. RESULTS: In the majority, an intraluminal thrombus of placental
      origin is the most probable hypothesis, while in the remaining ones, one can
      reasonably presume a direct vessel wall injury related to a traumatic delivery,
      yet generally unproven by imaging. CONCLUSION: We hypothesize that most of these
      cases share similar pathophysiology with the more common perinatal arterial
      ischemic stroke but differ by a persistent identified thrombus in the carotid
      artery at the time of first imaging, leading to a more severe and extended
      ischemic damage responsible for an adverse neurological outcome.

PMID- 27025301
TI  - Paediatric patients with sudden vision impairment - An overview of MRI findings.
AB  - PURPOSE: Sudden visual impairment in children occurs sporadically but, when
      present, needs urgent attention. Optimal management strategies and timely
      recognition are required. Often psychogenic disorders are the cause in school-age
      children; however, this is a diagnosis of exclusion. Therefore, MRI plays an
      important role in ruling out pathology along the optic pathways or helping with
      the diagnosis of underlying life threatening diseases, such as hydrocephalus or
      intracranial mass. The purpose of this study was first to evaluate non-traumatic
      (tumoural and non-tumoural) causes of acute vision impairment; and, second, to
      assess whether conventional cerebral and orbital MR imaging is helpful for
      children with sudden visual impairment. PATIENTS AND METHODS: We retrospectively
      analysed the MRI scans and clinical findings of 95 children (47 male, 48 female;
      median age: 12.5 years, range: from 2 to 17 years) who presented symptoms of
      monocular or bilateral acute vision impairment. RESULTS: Patients with acute
      visual impairment were usually older than 7 years. In 36% of the patients a
      correlation between the MRI findings and the clinical symptoms was found. The
      most common causes of visual impairment were: infectious diseases (16%), migraine
      (12%), autoimmune diseases (11%), optic nerve neuritis with unknown aetiology
      (8%), neoplasms (8%), idiopathic intracranial hypertension (5%) and orthostatic
      hypotension (4%). Still, in 23% of the patients the cause remained unclear.
      CONCLUSION: Acute vision impairment is frequently caused by infectious diseases,
      migraine, autoimmune diseases or tumours in children. MRI is highly recommended,
      especially in the case of children younger than 5 years of whom clinical
      assessment can be difficult.

PMID- 27025302
TI  - Mid Term Bleeding Risk Prediction After an Acute Coronary Syndrome: An Unsolved
      Question.

PMID- 27025303
TI  - Recent Scientific Evidence and Technical Developments in Cardiovascular Computed
      Tomography.
AB  - In recent years, coronary computed tomography angiography has become an
      increasingly safe and noninvasive modality for the evaluation of the anatomical
      structure of the coronary artery tree with diagnostic benefits especially in
      patients with a low-to-intermediate pretest probability of disease. Currently,
      increasing evidence from large randomized diagnostic trials is accumulating on
      the diagnostic impact of computed tomography angiography for the management of
      patients with acute and stable chest pain syndrome. At the same time, technical
      advances have substantially reduced adverse effects and limiting factors, such as
      radiation exposure, the amount of iodinated contrast agent, and scanning time,
      rendering the technique appropriate for broader clinical applications. In this
      work, we review the latest developments in computed tomography technology and
      describe the scientific evidence on the use of cardiac computed tomography
      angiography to evaluate patients with acute and stable chest pain syndrome. 

PMID- 27025304
TI  - Goal motives and multiple-goal striving in sport and academia: A person-centered
      investigation of goal motives and inter-goal relations.
AB  - OBJECTIVES: This investigation extended the goal striving literature by examining
      motives for two goals being pursued simultaneously. Grounded in self
      determination theory, we examined how student-athletes' motives for their
      sporting and academic goals were associated with inter-goal facilitation and
      interference. DESIGN: Cross-sectional survey. METHODS: UK university student
      athletes (n=204) identified their most important sporting and academic goals.
      They then rated their extrinsic, introjected, identified and intrinsic motives
      for these goals and completed questionnaires assessing inter-goal facilitation
      and interference. RESULTS: Using a person-centered approach via latent profile
      analysis, we identified three distinct profiles of goal motives. Auxiliary
      analyses showed that the profile with high identified motives for both goals
      reported greater inter-goal facilitation. CONCLUSIONS: Extending the previous
      literature, the findings demonstrate the benefits of autonomous motives when
      simultaneously pursing goals in sport and academia.

PMID- 27025305
TI  - Echocardiographic diagnosis and necropsy findings of a congenital ventricular
      septal defect in a stranded harbor porpoise.
AB  - A live-stranded harbor porpoise Phocoena phocoena was found on the west coast of
      the Dutch island Texel (North Sea) and transported to a rehabilitation center for
      small cetaceans, where it underwent a veterinary health check. Cardiac
      auscultation revealed a systolic cardiac murmur with the point of maximal
      intensity in the right hemithorax with an intensity of IV out of VI.
      Transthoracic echocardiography revealed a congenital ventricular septal defect
      with left-to-right shunting. Because the left atrium was not dilated according to
      the reference range of canine left atrium to aortic ratio, the presence of
      congestive heart failure was considered very unlikely. Therefore, this congenital
      cardiac anomaly was thought to be a clinically non-relevant incidental finding
      and would not explain the weakness, coughing, anorexia, vomiting, and diarrhea.
      Because the animal was still unable to swim or eat by itself after 2 wk of
      supportive care, it was euthanized. Post-mortem examination confirmed the
      presence of a ventricular septal defect. The weight of the heart relative to the
      animal's length was greater than expected, using linear regression analysis on
      the lengths and cardiac weights of 71 other stranded wild harbor porpoises
      without macroscopic cardiac pathologic changes. This finding suggests that the
      left ventricle had an eccentric hypertrophy because of volume overload resulting
      from the intracardiac shunt. This is the first report of a congenital cardiac
      anomaly and its ante-mortem diagnosis in this species. Data presented for the
      other 71 harbor porpoises may provide reference values for this species.

PMID- 27025306
TI  - Histopathological alterations of the heart in fish: proposal for a standardized
      assessment.
AB  - Histopathological alterations in the heart are often reported in fish as a result
      of exposure to a variety of chemical compounds. However, researchers presently
      lack a standardized method for the evaluation of histopathological alterations in
      the cardiovascular system of fish and the calculation of an 'organ index'.
      Therefore, we designed a method for a standardized assessment and evaluation of
      histopathological alterations in the heart of fish. As a model species, we used
      rainbow trout Oncorhynchus mykiss, but the protocol was also successfully applied
      to other fish species belonging to different taxonomic orders. To test the
      protocol, we re-evaluated sections of atenolol-exposed and unexposed rainbow
      trout obtained in a previous study. The results were in accordance with those
      previously published, demonstrating the applicability of the protocol. The
      protocol provides a universal method for the comparative evaluation of
      histopathological changes in the heart of fish.

PMID- 27025307
TI  - Distribution, prevalence, and pathology of a microsporidian infecting freshwater
      sculpins.
AB  - Microsporidian infections are common in many fish species, yet detailed studies
      of these parasites in ecologically important wild populations are rare.
      Phylogenetic analysis using rDNA sequence data and parasite morphology indicate
      that mottled sculpin Cottus bairdii and slimy sculpin C. cognatus are hosts for
      Glugea sp. microsporidia in the northern USA. Glugea sp. is common in the
      Michigan populations sampled for this study, and prevalence was >= 70% in 4 of 6
      infected populations (range -4 to 80%). Glugea sp. infection causes the formation
      of xenomas associated with the body wall, fat body, gonads, and kidneys.
      Infections range from mild to very heavy, with variable xenoma numbers and sizes.
      Female sculpin experience heavier infections and more frequent infection of the
      gonads relative to males. Glugea sp. is transmitted horizontally between hosts
      through ingestion of spores. Vertical transmission may also be possible, either
      by spores infecting eggs directly or by spores contaminating the surface of eggs
      in the ovary or in the nest. The frequency and route of vertical transmission
      requires further study, but if it occurs, it may partly explain the high
      prevalence of infection. Our study combined with previous research suggests that
      additional molecular data and cross-infection experiments should be conducted to
      clarify species designations in the genus Glugea.

PMID- 27025308
TI  - Morphology, histology and phylogeny of Henneguya sinova sp. nov. (Myxobolidae:
      Myxozoa) infecting gills of Parablennius tentacularis in the Black Sea, Turkey.
AB  - Myxosporeans of the genus Henneguya have a global distribution and infect organs
      and tissues of both marine and freshwater fishes. Here we describe the
      morphological, histological and molecular characteristics of Henneguya sinova sp.
      nov. parasitizing the gill arches of tentacled blenny Parablennius tentacularis
      (Perciformes: Blenniidae) collected from the coast of Sinop on the Black Sea in
      Turkey. Several oval whitish plasmodia of different sizes in the gill arches of
      fish were found. The mature spores were rounded oval in frontal view, with a mean
      (range) total length 57.5 (51.5-68.0) um; the spore body was 11.7 (11.3-12.0) um
      in length by 7.6 (7.3-8.3) um in width and 6.7 (6.6-6.8) um in thickness. The
      caudal appendages, measuring 46.0 (40.0-55.0) um in length, were very thin at the
      tapered end. The prevalence of infection by H. sinova sp. nov. was 35.5%.
      Phylogenetic analysis of nuclear small subunit ribosomal DNA (SSU rDNA) clearly
      suggested H. sinova as a new species which is clustered within the marine
      Henneguya lineage. Pairwise nucleotide similarities and DNA distance values of
      SSU rDNA between H. sinova sp. nov. and other related Henneguya species also
      supported this suggestion.

PMID- 27025309
TI  - Iron assimilation and siderophore production by Vibrio ordalii strains isolated
      from diseased Atlantic salmon Salmo salar in Chile.
AB  - Vibrio ordalii is the causative agent of vibriosis in several cultured salmonid
      species worldwide. Despite its impact on aquaculture, relatively little
      information is available about its virulence factors. The present study
      demonstrates for the first time that V. ordalii possesses different systems of
      iron acquisition, one involving siderophore synthesis and another one that uses
      direct binding of heme to use iron. Using 6 strains of V. ordalii from Atlantic
      salmon Salmo salar and the V. ordalii type strain, we could demonstrate that all
      strains could grow in presence of the chelating agent 2,2'-dipyridyl and produced
      siderophores in solid and liquid media. Cross-feeding assays among V. ordalii
      strains evidenced variability in the siderophores produced. Bioassays and PCR
      data suggest that V. ordalii could produce a siderophore with a structure similar
      to piscibactin, although the production of a second siderophore in certain
      strains cannot be discarded. Furthermore, all strains were able to use hemin and
      hemoglobin as the only iron sources, although the cell yield was higher when
      using hemoglobin. A hemin-binding assay indicated the presence of constitutive
      heme-binding molecules at the cell surface of V. ordalii. Virulence tests using
      rainbow trout as a model of infection revealed a clear relationship between iron
      uptake ability and pathogenicity in V. ordalii.

PMID- 27025310
TI  - Retrospective analysis of antibiotic treatments against piscirickettsiosis in
      farmed Atlantic salmon Salmo salar in Chile.
AB  - Piscirickettsiosis is the most prevalent salt-water infectious disease in farmed
      salmonids in Chile. Antimicrobials are used to treat this disease; however, there
      is growing concern about the poor response to therapeutants on some fish farms.
      The objective of this study was to assess whether factors such as type of
      antibiotic used, average fish weight, temperature at the beginning of the
      treatment, and mortality at the time of treatment administration affect the
      probability of treatment failure against piscirickettsiosis. Pen-level treatment
      and production information for the first treatment event from 2014 pens on 118
      farms was used in a logistic mixed model to assess treatment failure. We defined
      a failed treatment as when the average mortality 3 wk after the treatment was
      above 0.1%. Farm and company were included in the model as random effects. We
      found that the antibiotic product, mortality level before the treatment, and fish
      weight at the start of the treatment all had a significant effect on treatment
      outcome. Our results suggest that antibiotic treatment success is higher if the
      treatment is administered when mortality associated with piscirickettsiosis is
      relatively low. We discuss the effect of weight on treatment success and its
      potential relationships with husbandry practices and drug pharmacokinetics.

PMID- 27025311
TI  - Immunostimulatory effects of prolactin on TLR1 and TLR5M in SHK-1 cells infected
      with Piscirickettsia salmonis.
AB  - The innate immune system is the first line of defense against infection by
      pathogens. It consists of various elements, including Toll-like receptors (TLRs),
      which recognize molecular patterns associated with pathogens and trigger the
      immune response, through activation of important transcription factors such as NF
      kappaB, which are usually found sequestered in the cytoplasm by IkappaBalpha
      until it receives the release signal. Piscirickettsia salmonis causes
      piscirickettsiosis or salmonid rickettsial septicemia, a disease of great
      importance in Chile, representing 79.4% of the secondary mortality in important
      species such as Salmo salar, which is reflected in the Chilean economy. Prolactin
      (PRL) is a peptide hormone which has immunomodulating functions in mammals and
      some fish. Olavarria et al. (2010, J Immunol 185:3873-3883) determined its
      ability to increase the respiratory burst, its relationship with the JAK/STAT
      pathway, and the expression of interleukin IL-1beta in Sparus aurata. Therefore,
      the present study was intended to establish a possible correlation and modulation
      between the signal transduction pathway of PRL (JAK/STAT), the pathways of NF
      kappaB, and TLRs, in an infection caused by P. salmonis in salmon head kidney
      (SHK-1) cells of S. salar. Stimulus with native PRL from S. salar was performed,
      and gene expression was analyzed for IL-1beta, IkappaBalpha, TLR1, and TLR5M
      (membrane-bound form). In addition, the effect of PRL in the nuclear
      translocation of the transcription factor NF-kappaB and the possible involvement
      of JAK2 were analyzed by using a pharmacological inhibitor of this kinase. The
      results show a positive modulation of PRL in all analyzed genes and a significant
      increase in the translocation of NF-kappaB, recording a maximum at 2 h post
      treatment, supporting the stimulatory hypothesis of PRL.

PMID- 27025312
TI  - Identification of a Mycobacterium sp. as the causative agent of orange nodular
      lesions in the Atlantic sea scallop Placopecten magellanicus.
AB  - The Atlantic sea scallop Placopecten magellanicus is an economically important
      species in the offshore fisheries on the east coast of the USA. Recently, animals
      collected from waters ranging from Massachusetts to Maryland have shown variably
      sized (up to 1 cm in diameter) orange nodular foci, predominantly in the adductor
      muscle tissue, but also in other organs. Histological evaluation of the nodular
      lesions showed rod-shaped bacteria that stain acid-fast positive and Gram
      positive. PCR methodology was employed to identify the causative organism of the
      nodules as a Mycobacterium sp. using analysis of the partial 16S gene and the 16S
      23S internal transcribed spacer region. Based upon genotypic findings, the
      causative bacterium fits well into the genus Mycobacterium.

PMID- 27025313
TI  - Filling a gap in the distribution of Batrachochytrium dendrobatidis: evidence in
      amphibians from northern China.
AB  - Chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) has been
      recognized as a major driver of amphibian declines worldwide. Central and
      northern Asia remain as the greatest gap in the knowledge of the global
      distribution of Bd. In China, Bd has recently been recorded from south and
      central regions, but areas in the north remain poorly surveyed. In addition, a
      recent increase in amphibian farming and trade has put this region at high risk
      for Bd introduction. To investigate this, we collected a total of 1284 non
      invasive skin swabs from wild and captive anurans and caudates, including free
      ranging, farmed, ornamental, and museum-preserved amphibians. Bd was detected at
      low prevalence (1.1%, 12 of 1073) in live wild amphibians, representing the first
      report of Bd infecting anurans from remote areas of northwestern China. We were
      unable to obtain evidence of the historical presence of Bd from museum amphibians
      (n = 72). Alarmingly, Bd was not detected in wild amphibians from the provinces
      of northeastern China (>700 individuals tested), but was widely present (15.1%,
      21 of 139) in amphibians traded in this region. We suggest that urgent
      implementation of measures is required to reduce the possibility of further
      spread or inadvertent introduction of Bd to China. It is unknown whether Bd in
      northern China belongs to endemic and/or exotic genotypes, and this should be the
      focus of future research.

PMID- 27025314
TI  - A snap shot of the short-term response of crustaceans to macrophyte detritus in
      the deep Oslofjord.
AB  - A test deployment of a time-lapse camera lander in the deep Oslofjord (431 m) was
      used to obtain initial information on the response of benthic fauna to macroalgal
      debris. Three macroalgal species were used on the lander baited plate: Fucus
      serratus, Saccharina latissima and Laminaria hyperborea and observed during 41.5
      hours. The deep-water shrimp Pandalus borealis were attracted to the macroalgae
      rapidly (3 min after the lander reached the seafloor), followed by amphipods.
      Shrimp abundances were significantly higher in areas covered by macroalgae
      compared to the adjacent seafloor and the number of shrimp visiting the
      macroalgae increased with time. Amphipods arrived 13 hours later and were
      observed mainly on decaying L. hyperborea. The abundance of amphipods on L.
      hyperborea increased rapidly, reaching a peak at 31 h after deployment. These
      initial observations suggest that debris from kelp forests and other macroalgal
      beds may play an important role in fuelling deep benthic communities in the outer
      Oslofjord and, potentially, enhance secondary production of commercial species
      such as P. borealis.

PMID- 27025315
TI  - Patient safety is not a luxury.

PMID- 27025316
TI  - Unite to end tuberculosis.

PMID- 27025317
TI  - Addressing the social determinants of health in young people.

PMID- 27025318
TI  - Defining new standards of care for men with prostate cancer.

PMID- 27025320
TI  - Sustainable development and global mental health--a Lancet Commission.

PMID- 27025319
TI  - Why are people living with HIV still dying of tuberculosis?

PMID- 27025322
TI  - WHO meeting thrashes out R&D strategy against Zika.

PMID- 27025323
TI  - France steps up warning measures for valproate drugs.

PMID- 27025324
TI  - Changing the game for multidrug-resistant tuberculosis.

PMID- 27025325
TI  - Soumya Swaminathan: re-energising tuberculosis research in India.

PMID- 27025326
TI  - Tuberculosis control.

PMID- 27025327
TI  - Global platform to inform investments for health R&D.

PMID- 27025328
TI  - Tuberculosis control.

PMID- 27025329
TI  - Tuberculosis control.

PMID- 27025330
TI  - Tuberculosis control.

PMID- 27025331
TI  - Tuberculosis control.

PMID- 27025332
TI  - E-cigarettes are less harmful than smoking.

PMID- 27025333
TI  - Tuberculosis control.

PMID- 27025334
TI  - Department of Error.

PMID- 27025336
TI  - Department of Error.

PMID- 27025338
TI  - Unique nonstructural dysfunction of the omnicarbon valve: case report.
AB  - BACKGROUND: Pannus formation may disturb the leaflet movement of the prosthetic
      valve. CASE PRESENTATION: A 61-year-old woman presented with exertional dyspnea.
      She had undergone mitral valve replacement with a bioprosthetic valve 31 years
      ago, which was replaced with a tilting disc valve 22 years ago. The present
      laboratory findings revealed hemolytic anemia. Echocardiography showed an
      increased mean pressure gradient through the mitral valve and moderate to severe
      regurgitation around the minor orifice of the tilting disc valve. She therefore
      underwent a third operation. Pannus formation was found on the prosthetic valve
      ring, but it did not obliterate the prosthetic valve orifice. After removing the
      valve, the posterior wall of the left ventricle was seen to be associated with
      thickened endocardium. A bileaflet valve was implanted. Postoperative
      echocardiography showed that the implanted valve functioned well. CONCLUSIONS:
      Nonstructural dysfunction of the mechanical heart valve might occur long after
      operation. These changes are particularly observed with a tilting disc valve.

PMID- 27025339
TI  - Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine
      conjugates with amino acid linkers.
AB  - Novel fluoroquinolone-pyrazine conjugates 7a-h with amino acid linkers were
      synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial
      bioassay showed that the synthesized bis-conjugates have antimicrobial properties
      comparable to the parent drugs. Compound 7h showed superior antibacterial
      activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6 MUM
      and 149.3 MUM, respectively). This matched well with the estimated values
      obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67 MUM and 92.9 MUM,
      respectively).

PMID- 27025340
TI  - Synthesis of a dansyl-labeled inhibitor of 17beta-hydroxysteroid dehydrogenase
      type 3 for optical imaging.
AB  - The steroidogenic enzyme 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3)
      is a therapeutic target in the management of androgen-sensitive diseases such as
      prostate cancer and benign prostate hyperplasia. In this Letter, we designed and
      synthesized the first fluorescent inhibitor of this enzyme by combining a
      fluorogenic dansyl moiety to the chemical structure of a known inhibitor of
      17beta-HSD3. The synthesized compound 3 is a potent fluorogenic compound
      (lambdaex=348 nm and lambda em=498 nm). It crosses the cell membrane, keeps its
      fluorescent properties and is distributed inside the LNCaP cells overexpressing
      17beta-HSD3, where it inhibits the transformation of 4-androstene-3,17-dione into
      the androgen testosterone (IC50=262 nM).

PMID- 27025337
TI  - Empirical tuberculosis therapy versus isoniazid in adult outpatients with
      advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open
      label randomised controlled trial.
AB  - BACKGROUND: Mortality within the first 6 months after initiating antiretroviral
      therapy is common in resource-limited settings and is often due to tuberculosis
      in patients with advanced HIV disease. Isoniazid preventive therapy is
      recommended in HIV-positive adults, but subclinical tuberculosis can be difficult
      to diagnose. We aimed to assess whether empirical tuberculosis treatment would
      reduce early mortality compared with isoniazid preventive therapy in high-burden
      settings. METHODS: We did a multicountry open-label randomised clinical trial
      comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV
      positive outpatients initiating antiretroviral therapy with CD4 cell counts of
      less than 50 cells per MUL. Participants were recruited from 18 outpatient
      research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia,
      India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for
      tuberculosis using a symptom screen, locally available diagnostics, and the
      GeneXpert MTB/RIF assay when available before inclusion. Study candidates with
      confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver
      function tests 2.5 times the upper limit of normal or less, a creatinine
      clearance of at least 30 mL/min, and a Karnofsky score of at least 30.
      Participants were randomly assigned (1:1) to either the empirical group
      (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid
      preventive therapy group (antiretroviral therapy and isoniazid preventive
      therapy). The primary endpoint was survival (death or unknown status) at 24 weeks
      after randomisation assessed in the intention-to-treat population. Kaplan-Meier
      estimates of the primary endpoint across groups were compared by the z-test. All
      participants were included in the safety analysis of antiretroviral therapy and
      tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number
      NCT01380080. FINDINGS: Between Oct 31, 2011, and June 9, 2014, we enrolled 850
      participants. Of these, we randomly assigned 424 to receive empirical
      tuberculosis therapy and 426 to the isoniazid preventive therapy group. The
      median CD4 cell count at baseline was 18 cells per MUL (IQR 9-32). At week 24, 22
      (5%) participants from each group died or were of unknown status (95% CI 3.5-7.8)
      for empirical group and for isoniazid preventive therapy (95% CI 3.4-7.8);
      absolute risk difference of -0.06% (95% CI -3.05 to 2.94). Grade 3 or 4 signs or
      symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%)
      participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory
      abnormalities occurred in 99 (23%) participants in the empirical group and 97
      (23%) participants in the isoniazid preventive therapy group. INTERPRETATION:
      Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with
      isoniazid preventive therapy in outpatient adults with advanced HIV disease
      initiating antiretroviral therapy. The low mortality rate of the trial supports
      implementation of systematic tuberculosis screening and isoniazid preventive
      therapy in outpatients with advanced HIV disease. FUNDING: National Institutes of
      Allergy and Infectious Diseases through the AIDS Clinical Trials Group.

PMID- 27025342
TI  - A convenient synthesis of 5'-triantennary N-acetyl-galactosamine clusters based
      on nitromethanetrispropionic acid.
AB  - A convenient method for the synthesis of several triantennary GalNAc clusters
      based on a nitromethanetrispropionic acid core was developed. The synthetic
      approach involves pentafluorophenolic ester intermediates which can be used in a
      one-pot, seven reaction procedure to quickly prepare a variety of triantennary
      GalNAc conjugated ASOs. The GalNAc clusters were conjugated to the 5'-end of an
      antisense oligonucleotide and evaluated for activity in primary mouse hepatocytes
      where they showed ~10-fold improvement in activity.

PMID- 27025341
TI  - Metabolic investigation on ZL006 for the discovery of a potent prodrug for the
      treatment of cerebral ischemia.
AB  - 4-((3,5-Dichloro-2-hydroxybenzyl)amino)-2-hydroxybenzoic acid (ZL006, 1) is a
      small-molecular inhibitor of the nNOS/PSD-95 interaction, that is under
      preclinical evaluation stage for cerebral ischemia. However, the fast metabolism
      and low permeability across the blood brain barrier (BBB) have restricted its
      further use. In this manuscript, the mass spectroscopy analysis showed that ZL006
      mainly combined with glucuronic acid in mice plasma, which accelerated its
      metabolism and elimination. Hence, six ZL006 analogs were designed according to
      the probable metabolism sites of ZL006, and featured the alkylation at phenolic
      hydroxyl, secondary amine and carboxyl groups. These compounds were synthesized
      in moderate to good yields, and fully characterized with (1)H NMR and MS. Further
      metabolism investigation of ZL006 analogs showed that phenolic hydroxyl group of
      aromatic ring A was the major conjugation site with glucuronic acid, and ZL006
      cyclohexyl ester (6) had a better permeability across BBB, which was a potent
      prodrug for cerebral ischemia. 

PMID- 27025343
TI  - Design and synthesis of novel quinoxaline derivatives as potential candidates for
      treatment of multidrug-resistant and latent tuberculosis.
AB  - Twenty-four quinoxaline derivatives were evaluated for their antimycobacterial
      activity using BacTiter-Glo microbial cell viability assay. Five compounds showed
      MIC values <3.1 MUM and IC50 values<1.5 MUM in primary screening and therefore,
      they were moved on for further evaluation. Compounds 21 and 18 stand out, showing
      MIC values of 1.6 MUM and IC50 values of 0.5 and 1.0 MUM, respectively. Both
      compounds were the most potent against three evaluated drug-resistant strains.
      Moreover, they exhibited intracellular activity in infected macrophages,
      considering log-reduction and cellular viability. In addition, compounds 16 and
      21 were potent against non-replicating Mycobacterium tuberculosis and compound 21
      was bactericidal. Therefore, quinoxaline derivatives could be considered for
      making further advances in the future development of antimycobacterial agents.

PMID- 27025344
TI  - Natural products as sources of new fungicides (III): Antifungal activity of 2,4
      dihydroxy-5-methylacetophenone derivatives.
AB  - A series of new 2,4-dihydroxy-5-methylacetophenone 2 derivatives were
      synthesized, and characterized by (1)H, (13)C NMR and ESI-MS. Their antifungal
      activities were evaluated in vitro against five important plant fungal pathogens
      including Cytospora sp., Glomerella cingulate, Pyricularia oryzaecar, Botrytis
      cinerea and Alternaria solani by the mycelial growth inhibitory rate assay.
      Compounds 2b-d, 2g and 2h displayed a broad-spectrum activity. The logP value of
      these active compounds is ranging from 1.71 to 2.54. Especially, isopropyl ketone
      2g (logP 2.27) was found to be the most active to the tested organisms with IC50
      values of 17.28-32.32 MUg/mL. The results suggest that compound 2g might be a
      promising candidate in the development of new agrochemical antifungal agents.
      Preliminary structure-activity relationship (SAR) studies of the acetophenone
      derivatives are also discussed.

PMID- 27025345
TI  - Modification on the O-glucoside of Sergliflozin-A: A new strategy for SGLT2
      inhibitor design.
AB  - Poor pharmacokinetic stability is one of the issues of O-glucoside SGLT2
      inhibitors in clinical trials, hence C-glucoside inhibitors have been developed
      and extensively applied. Herein, we provided an alternative approach to improve
      the pharmacokinetic stability of such inhibitors. Nine derivatives of
      Sergliflozin-A with modifications on the O-glucoside fragment were prepared,
      among which the 4-O-methyl derivative exhibited similar pharmacodynamics potency
      in excreted glucose urine test. Most attractively, significantly increased
      pharmacokinetic stability was observed for 4-O-methyl derivative of O-glucosides.
      This work proved that modification on the O-glucoside fragment could be a
      promising approach to the future SGLT2 inhibitor design. 

PMID- 27025346
TI  - Childhood atopic dermatitis and risk of attention deficit/hyperactivity disorder:
      A cohort study.

PMID- 27025347
TI  - Circulating microRNAs as biomarkers in patients with allergic rhinitis and
      asthma.
AB  - BACKGROUND: MicroRNAs (miRNAs) are emerging as important regulatory molecules
      that might be involved in the pathogenesis of various diseases. Circulating
      miRNAs might be noninvasive biomarkers to diagnose and characterize asthma and
      allergic rhinitis (AR). OBJECTIVE: We sought to determine whether miRNAs are
      differentially expressed in the blood of asthmatic patients compared with those
      in the blood of nonasthmatic patients with AR and nonallergic nonasthmatic
      subjects. Furthermore, we sought to establish whether miRNAs could be used to
      characterize or subtype asthmatic patients. METHODS: Expression of plasma miRNAs
      was measured by using real-time quantitative PCR in 35 asthmatic patients, 25
      nonasthmatic patients with AR, and 19 nonallergic nonasthmatic subjects.
      Differentially expressed miRNAs were identified by using Kruskal-Wallis 1-way
      ANOVA with Bonferroni P value adjustment to correct for multiple comparisons. A
      random forest classification algorithm combined with a leave-one-out cross
      validation approach was implemented to assess the predictive capacities of the
      profiled miRNAs. RESULTS: We identified 30 miRNAs that were differentially
      expressed among healthy, allergic, and asthmatic subjects. These miRNAs fit into
      5 different expression pattern groups. Among asthmatic patients, miRNA expression
      profiles identified 2 subtypes that differed by high or low peripheral eosinophil
      levels. Circulating miR-125b, miR-16, miR-299-5p, miR-126, miR-206, and miR-133b
      levels were most predictive of allergic and asthmatic status. CONCLUSIONS:
      Subsets of circulating miRNAs are uniquely expressed in patients with AR and
      asthmatic patients and have potential for use as noninvasive biomarkers to
      diagnose and characterize these diseases.

PMID- 27025348
TI  - Revealing the role of molecular rigidity on the fragility evolution of glass
      forming liquids.
AB  - If quenched fast enough, a liquid is able to avoid crystallization and will
      remain in a metastable supercooled state down to the glass transition, with an
      important increase in viscosity upon further cooling. There are important
      differences in the way liquids relax as they approach the glass transition, rapid
      or slow variation in dynamic quantities under moderate temperature changes, and a
      simple means to quantify such variations is provided by the concept of fragility.
      Here, we report molecular dynamics simulations of a typical network-forming
      glass, Ge-Se, and find that the relaxation behaviour of the supercooled liquid is
      strongly correlated to the variation of rigidity with temperature and the spatial
      distribution of the corresponding topological constraints, which ultimately
      connect to the fragility minima. This permits extending the fragility concept to
      aspects of topology/rigidity, and to the degree of homogeneity of the atomic
      scale interactions for a variety of structural glasses. 

PMID- 27025349
TI  - Applying Human Factors Principles to Mitigate Usability Issues Related to
      Embedded Assumptions in Health Information Technology Design.
AB  - BACKGROUND: There is growing recognition that design flaws in health information
      technology (HIT) lead to increased cognitive work, impact workflows, and produce
      other undesirable user experiences that contribute to usability issues and, in
      some cases, patient harm. These usability issues may in turn contribute to HIT
      utilization disparities and patient safety concerns, particularly among "non
      typical" HIT users and their health care providers. Health care disparities are
      associated with poor health outcomes, premature death, and increased health care
      costs. HIT has the potential to reduce these disparate outcomes. In the computer
      science field, it has long been recognized that embedded cultural assumptions can
      reduce the usability, usefulness, and safety of HIT systems for populations whose
      characteristics differ from "stereotypical" users. Among these non-typical users,
      inappropriate embedded design assumptions may contribute to health care
      disparities. It is unclear how to address potentially inappropriate embedded HIT
      design assumptions once detected. OBJECTIVE: The objective of this paper is to
      explain HIT universal design principles derived from the human factors
      engineering literature that can help to overcome potential usability and/or
      patient safety issues that are associated with unrecognized, embedded assumptions
      about cultural groups when designing HIT systems. METHODS: Existing best
      practices, guidance, and standards in software usability and accessibility were
      subjected to a 5-step expert review process to identify and summarize those best
      practices, guidance, and standards that could help identify and/or address
      embedded design assumptions in HIT that could negatively impact patient safety,
      particularly for non-majority HIT user populations. An iterative consensus-based
      process was then used to derive evidence-based design principles from the data to
      address potentially inappropriate embedded cultural assumptions. RESULTS: Design
      principles that may help identify and address embedded HIT design assumptions are
      available in the existing literature. CONCLUSIONS: Evidence-based HIT design
      principles derived from existing human factors and informatics literature can
      help HIT developers identify and address embedded cultural assumptions that may
      underlie HIT-associated usability and patient safety concerns as well as health
      care disparities.

PMID- 27025350
TI  - Anti-trypanosomal compound, sagamilactam, a new polyene macrocyclic lactam from
      Actinomadura sp. K13-0306.
AB  - A new antibiotic, designated sagamilactam, was isolated from the cultured broth
      of Actinomadura sp. K13-0306 by Diaion HP-20, silica gel and octadecylsilane
      column chromatography followed by purification by HPLC. The chemical structure of
      the new compound was elucidated by spectroscopic analyses, including NMR and MS.
      The structure of sagamilactam proved to be a new compound consisting of a
      polyunsaturated and polyoxygenated 34-membered macrocyclic lactam containing
      diene, triene and tetraene conjugated olefins and a decalin moiety. Sagamilactam
      showed antitrypanosomal activity with an IC50 value of 0.25+/-0.11 MUM.

PMID- 27025351
TI  - Anti-Helicobacter pylori activity of some newly synthesized derivatives of
      xanthone.
AB  - A series of 20 xanthone derivatives was synthesized and evaluated for anti
      Helicobacter pylori (H. pylori) activity. Qualitative and quantitative in vitro
      tests using the Kirby-Bauer method (agar disc-diffusion method) were performed.
      The tested compounds were screened against clarithromycin- and/or metronidazole
      resistant strains of H. pylori. As a reference, Gram-positive (Staphylococcus
      aureus) and Gram-negative (Escherichia coli) bacterial strains were examined. On
      the basis of microbiological assays, xanthones can be considered as potential
      anti-H. pylori agents. They displayed significant activity against the examined
      strains, which was higher against the bacteria resistant to metronidazole than
      clarithromycin. The lowest MIC values ranging up to 20 mg l-1 were observed for
      the following compounds: 3, 4, 8, 9, 12, 19 (against the metronidazole-resistant
      strains) and the compound 10 (against the clarithromycin-resistant strain). These
      preliminary results for screening of xanthone derivatives form a part of an
      ongoing study of the structure-activity relationships of a large group of
      compounds. Microbiological assays will be conducted afterwards to determine the
      mechanism of xanthones' action against H. pylori.

PMID- 27025353
TI  - Influence of humidity on the initial emittable concentration of formaldehyde and
      hexaldehyde in building materials: experimental observation and correlation.
AB  - Humidity is one of the main environmental factors affecting the emission rate and
      key parameters of formaldehyde and volatile organic compounds (VOCs) from
      building materials. Meanwhile, the initial emittable concentration (Cm,0) is
      proved to be the most sensitive key parameter to the emission behaviours.
      However, there is no report on the relationship between humidity and Cm,0. In
      this paper, Cm,0 of formaldehyde and hexaldehyde from a type of medium density
      fiberboard in absolute humidity (AH) range of 4.6-19.6 g/m(3) at 25  degrees C
      were tested by virtue of a C-history method. Experimental results indicate that
      Cm,0 is dramatically dependent on AH, increased by 10 and 2 times for
      formaldehyde and hexaldehyde when AH rising from 4.6 g/m(3) to 19.6 g/m(3). A
      linear relationship between the logarithm of Cm,0 and AH is obtained based on the
      measured results. In addition, a correlation characterizing the association of
      emission rate and AH is derived. The effectiveness of the correlation is verified
      with our experimental results as well as data from literature. With the
      correlations, the Cm,0 or emission rate different from the test AH conditions can
      be conveniently obtained. This study should be useful for predicting the emission
      characteristics of humidity changing scenarios and for source control.

PMID- 27025352
TI  - MIC score, a new tool to compare bacterial susceptibility to antibiotics
      application to the comparison of susceptibility to different penems of clinical
      strains of Pseudomonas aeruginosa.
AB  - This study aimed to compare the susceptibility to carbapenems (imipenem,
      meropenem and doripenem) of clinical strains of Pseudomonas aeruginosa. It also
      studied whether susceptibility to imipenem or meropenem could predict, reliably,
      susceptibility to doripenem. Pseudomonal strains were collected from respiratory
      specimens, half of them from cystic fibrosis patients. MICs were determined
      according to European Committee on Antimicrobial Susceptibility Testing
      recommendations. Carbapenems were compared according to the susceptible,
      intermediate or resistant categories. A new approach also allowed comparing these
      carbapenems in a 'MIC score' taking into account the differences in breakpoints
      between drugs. One hundred thirty-nine strains were studied. They were found to
      be statistically more susceptible to meropenem than to the two other drugs.
      However, this difference was small: less than one dilution between the agents.
      This study also highlighted a significant correlation between susceptibility to
      penems taken in pairs. However, susceptibility to imipenem or meropenem did not
      reliably predict susceptibility to doripenem. Despite potential differences in
      resistance mechanisms, the Pseudomonas aeruginosa strains showed close
      susceptibility to three carbapenems. This was true for both cystic fibrosis
      patients and others. However, there were variations between strains. That
      justifies MICs to be determined for each of the three penems. This might be
      useful in case of elevated MICs and/or for potentially difficult-to-treat
      infections such as pneumonia in patients with cystic fibrosis patients.

PMID- 27025354
TI  - Charge carrier coherence and Hall effect in organic semiconductors.
AB  - Hall effect measurements are important for elucidating the fundamental charge
      transport mechanisms and intrinsic mobility in organic semiconductors. However,
      Hall effect studies frequently reveal an unconventional behavior that cannot be
      readily explained with the simple band-semiconductor Hall effect model. Here, we
      develop an analytical model of Hall effect in organic field-effect transistors in
      a regime of coexisting band and hopping carriers. The model, which is supported
      by the experiments, is based on a partial Hall voltage compensation effect,
      occurring because hopping carriers respond to the transverse Hall electric field
      and drift in the direction opposite to the Lorentz force acting on band carriers.
      We show that this can lead in particular to an underdeveloped Hall effect
      observed in organic semiconductors with substantial off-diagonal thermal
      disorder. Our model captures the main features of Hall effect in a variety of
      organic semiconductors and provides an analytical description of Hall mobility,
      carrier density and carrier coherence factor. 

PMID- 27025355
TI  - Percutaneous Renal Biopsies for Small Renal Masses: Complex Tumors on Nephrometry
      Should Be the First Targets.
AB  - OBJECTIVE: To assess the diagnostic yield, accuracy, and complications rate for
      computed tomography (CT)-guided renal biopsies for solid renal masses (SRM); to
      analyze predictive factors for diagnostic biopsies. PATIENTS AND METHODS: We
      performed a single-center, retrospective study based on a pathologic database
      query for CT-guided, percutaneous renal biopsies. Inclusion criteria included
      presence of SRM; exclusion criteria included the presence of metastases, non-cT1a
      or higher cancer (> 4 cm), and non-CT-guided techniques. Of 119 patients who
      underwent renal biopsies, 40 (34%) were excluded from the study; 79 (66%) biopsy
      outcomes were analyzed. Clinical, radiologic (RENAL score), and pathologic
      features were reported. Differences between contributive and noncontributive
      biopsies were tested with Mann-Whitney U or chi-square tests, as appropriate.
      Multiple-variable analyses searching for predicting factors of biopsy
      contribution were performed with binary logistic regressions. RESULTS: CT-guided
      renal biopsies for SRM present a high yield (88.6%) and high accuracy for
      differentiating malignant from benign tumors (96%). They are less accurate for
      histologic subtype (93%) and unreliable for Fuhrman grading (64%). CT-guided
      renal biopsy is safe (minor complication rate, 2.5%) and helped prevent
      unnecessary surgery in 30.4% of the cohort. Tumor complexity with high RENAL
      score was a predictive factor (P = .02) of contributive biopsy. CONCLUSION: SRM
      biopsy is a safe, reliable procedure that can help determine the best treatment
      strategy for patients. It seems more beneficial for nephrometry complex tumors
      when surgical extirpation is more likely to be complicated. SRM biopsy might be
      encouraged in clinical practice for complex tumors.

PMID- 27025356
TI  - Development and validation of an oligonucleotide ligation assay to detect
      lamivudine resistance in hepatitis B virus.
AB  - Treatment of chronic hepatitis B virus (HBV) infection with lamivudine
      monotherapy rapidly selects mutant variants in a high proportion of individuals.
      Monitoring lamivudine resistance by consensus sequencing is costly and
      insensitive for detection of minority variants. An oligonucleotide ligation assay
      (OLA) for HBV lamivudine-resistance was developed and compared to consensus
      sequencing. Both assays detected drug resistance mutations in 35/64 (54.7%)
      specimens evaluated, and OLA detected minority mutants in an additional six
      (9.4%). OLA may offer a sensitive and inexpensive alternative to consensus
      sequencing for detection of HBV drug resistance in resource-limited settings. 

PMID- 27025357
TI  - Two-way molecular ligation for efficient conversion of monomeric hepatitis B
      virus DNA constructs into tandem dimers.
AB  - Replication of the 3.2-kb hepatitis B virus (HBV) genome is driven by the
      covalently closed circular (ccc) DNA in the nucleus, from which four classes of
      co-terminal RNAs are transcribed. Genome replication requires just the 3.5-kb
      pregenomic RNA, which is terminally redundant. Cloning the full-length HBV genome
      into a vector disrupts its continuity, thus preventing genome replication at the
      step of pregenomic RNA transcription. This can be overcome by converting the
      monomeric construct into a tandem dimer, yet the need to ligate two molecules of
      the HBV genome with vector DNA makes it inefficient and even unsuccessful. To
      overcome this problem we partially digested the monomeric construct with the
      unique restriction enzyme used for cloning, and dephosphorylated the linearized
      monomer before its ligation with another copy of the HBV genome. Alternatively,
      the monomer was linearized at another unique restriction site inside the HBV
      genome, followed by its dephosphorylation and ligation with another copy of the
      HBV genome linearized at the same site. These approaches of two-way molecular
      ligation greatly improved the efficiency of dimer formation with about 50% of the
      bacterial colonies screened harboring tandem dimers. 

PMID- 27025358
TI  - Plastic surgical operative workload in major trauma patients following
      establishment of the major trauma network in England: A retrospective cohort
      study.
AB  - INTRODUCTION: The introduction of major trauma centres (MTCs) in England has led
      to 63% reduction in trauma mortality.(1) The role of plastic surgeons supporting
      these centres has not been quantified previously. This study aimed to quantify
      plastic surgical workload at an urban MTC to determine the contribution of
      plastic surgeons to major trauma care. METHODS: All Trauma Audit and Research
      Network (TARN)-recorded major trauma patients who presented to an urban MTC in
      2013 and underwent an operation were identified retrospectively. Patients who
      underwent plastic surgery were identified and the type and date of procedure(s)
      were recorded. The trauma operative workload data of another tertiary surgical
      specialty and local historical plastics workload data from pre-MTC go-live were
      collected for comparison. RESULTS: Of the 416 major trauma patients who required
      surgical intervention, 29% (n = 122) underwent plastic surgery. Of these
      patients, 43% had open lower limb fractures, necessitating plastic surgical
      involvement according to British Orthopaedic Association Standards for Trauma
      (BOAST) 4 guidance. The overall plastic surgery operative workload increased
      sevenfold post-MTC go-live. A similar proportion of the same cohort required
      neurosurgery (n = 115; p = 0.589). DISCUSSION: This study quantifies plastic
      surgery involvement in major trauma and demonstrates that plastic surgical
      operative workload is at least on par with other tertiary surgical specialties.
      It also reports one centre's experience of a significant change in plastic
      surgery activity following designation of MTC status. The quantity of plastic
      surgical operative workload in major trauma must be considered when planning
      major trauma service design and workforce provision, and for plastic surgical
      postgraduate training.

PMID- 27025359
TI  - Zwitterionic materials for antifouling membrane surface construction.
AB  - Membrane separation processes are often perplexed by severe and ubiquitous
      membrane fouling. Zwitterionic materials, keeping electric neutrality with
      equivalent positive and negative charged groups, are well known for their
      superior antifouling properties and have been broadly utilized to construct
      antifouling surfaces for medical devices, biosensors and marine coatings
      applications. In recent years, zwitterionic materials have been more and more
      frequently utilized for constructing antifouling membrane surfaces. In this
      review, the antifouling mechanisms of zwitterionic materials as well as their
      biomimetic prototypes in cell membranes will be discussed, followed by the survey
      of common approaches to incorporate zwitterionic materials onto membrane surfaces
      including surface grafting, surface segregation, biomimetic adhesion, surface
      coating and so on. The potential applications of these antifouling membranes are
      also embedded. Finally, we will present a brief perspective on the future
      development of zwitterionic materials modified antifouling membranes. STATEMENT
      OF SIGNIFICANCE: Membrane fouling is a severe problem hampering the application
      of membrane separation technology. The properties of membrane surfaces play a
      critical role in membrane fouling and antifouling behavior/performance.
      Antifouling membrane surface construction has evolved as a hot research issue for
      the development of membrane processes. Zwitterionic modification of membrane
      surfaces has been recognized as an effective strategy to resist membrane fouling.
      This review summarizes the antifouling mechanisms of zwitterionic materials
      inspired by cell membranes as well as the popular approaches to incorporate them
      onto membrane surfaces. It can help form a comprehensive knowledge about the
      principles and methods of modifying membrane surfaces with zwitterionic
      materials. Finally, we propose the possible future research directions of
      zwitterionic materials modified antifouling membranes.

PMID- 27025360
TI  - Prediction of bleeding and prophylactic platelet transfusions in cancer patients
      with thrombocytopenia.
AB  - Studies on markers for bleeding risk among thrombocytopenic cancer patients are
      lacking. This prospective observational cohort study investigated whether
      platelet parameters and a standardised bleeding questionnaire predicted bleeding
      or prophylactic platelet transfusions in patients with cancer and
      thrombocytopenia. Admitted adult patients with cancer and platelet count <80 *
      10(9)/L were enrolled, but excluded if they experienced surgery or trauma within
      7 days or platelet transfusion within 14 days. Patients were interviewed, blood
      samples collected and, subsequently, spontaneous bleeding and prophylactic
      platelet transfusion within 30 days were registered. Of 197 patients enrolled, 56
      (28%) experienced bleeding. In multivariate analyses, predictors of bleeding were
      infection (adjusted odds ratio (OR) = 2.65 and 95% confidence interval (95% CI)
      1.04-6.74); treatment with platelet inhibitors, heparin or warfarin OR = 2.34,
      95% CI 1.23-4.48; urea nitrogen OR = 1.15, 95% CI 1.07-1.25; creatinine OR =
      1.01, 95% CI 1.01-1.01; and haemoglobin OR = 0.62, 95% CI 0.41-0.93. Specific
      information regarding previous gastrointestinal bleeding OR = 3.33, 95% CI 1.19
      9.34 and haematuria OR = 3.00, 95% CI 1.20-7.52 predicted bleeding whereas the
      standardised bleeding questionnaire did not. Prophylactic platelet transfusions
      were administered to 97 patients. Predictors of prophylactic platelet
      transfusions were: platelet count OR = 0.96, 95% CI 0.94-0.97; fibrinogen OR =
      0.88, 95% CI 0.83-0.95; mean platelet volume OR = 0.69, 95% CI 0.49-0.97;
      platelet aggregometry with OR = 2.48, 95% CI 1.09-5.64 for collagen-induced
      platelet aggregation within the lowest quartile; and albumin OR = 1.07, 95% CI
      1.01-1.15. In conclusion, except for immature platelet fraction (IPF), platelet
      parameters predicted prophylactic platelet transfusion but not bleeding. Bleeding
      risk factors were previous haematuria or gastrointestinal bleeding, infection,
      antiplatelet or anticoagulant treatment, high urea nitrogen, low haemoglobin or
      high creatinine. 

PMID- 27025361
TI  - Water-Stable Anionic Metal-Organic Framework for Highly Selective Separation of
      Methane from Natural Gas and Pyrolysis Gas.
AB  - A 3D water-stable anionic metal-organic framework
      [Zn4(hpdia)2].[NH2(CH3)2].3DMF.4H2O (FJI-C4) was constructed based on an
      elaborate phosphorus-containing ligand 5,5'-(hydroxyphosphoryl)diisophthalic acid
      (H5hpdia). FJI-C4 with narrow one-dimensional (1D) pore channels exhibits high
      selectivity of C3H8/CH4 and C2H2/CH4. It is the first time for the MOF which
      contains phosphorus for selective separation of methane from natural gas and
      pyrolysis gas. 

PMID- 27025362
TI  - Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.
AB  - Many biological toxins are known to attack specific cell types, delivering their
      enzymatic payloads to the cytosol. This process can be manipulated by molecular
      engineering of chimeric toxins. Using toxins with naturally unlinked components
      as a starting point is advantageous because it allows for the development of
      payloads separately from the binding/translocation components. Here the
      Clostridium botulinum C2 binding/translocation domain was retargeted to neural
      cell populations by deleting its non-specific binding domain and replacing it
      with a C. botulinum neurotoxin binding domain. This fusion protein was used to
      deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery
      was quantified by flow cytometry and found to be dependent on artificial
      enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by
      confocal microscopy showed a dissociation of payloads from the early endosome
      indicating translocation of the chimeric toxin. The natural Clostridium botulinum
      C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa
      cells. In the presence of the fusion protein, native cytosolic enzymatic activity
      of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin
      may enable delivery of therapeutics to peripheral neurons and be of use in
      addressing experimental questions about neural physiology. 

PMID- 27025363
TI  - Computational identification and systematic classification of novel GRAS genes in
      Isatis indigotica.
AB  - Isatis indigotica Fort., belonging to Cruciferae, is one of the most commonly
      used plants in traditional Chinese medicine. The accumulation of the effective
      components of I. indigotica is related with its growth conditions. The GRAS genes
      are members of a multigene family of transcriptional regulators that play a
      crucial role in plant growth. Although the activities of many GRAS genes have
      long been recognized, only in recent years were some of them identified and
      functionally characterized in detail. In the present study, 41 GRAS genes were
      identified from I. indigotica through bioinformatics methods for the first time.
      They were classified into ten groups according to the classification of
      Arabidopsis and rice. The characterization, gene structure, conserved motifs,
      disordered N-terminal domains, and phylogenetic reconstruction of these GRASs
      were analyzed. Forty-three orthologous gene pairs were shared by I. indigotica
      and Arabidopsis, and interaction networks of these orthologous genes were
      constructed. Furthermore, gene expression patterns were investigated by analysis
      in methyl jasmonate (MeJA)-treated I. indigotica hairy roots based on RNA-seq
      data. In conclusion, this comprehensive analysis would provide rich resources for
      further studies of GRAS protein functions in this plant. 

PMID- 27025364
TI  - The spectrum-effect relationship-a rational approach to screening effective
      compounds, reflecting the internal quality of Chinese herbal medicine.
AB  - Since the chromatographic fingerprint was introduced, it has been accepted by
      many countries to assess the quality and authenticity of Chinese herbal medicine
      (CHM). However, solely using the chromatographic fingerprint to assay numerous
      chemicals is not suitable for the assessment of the whole internal quality and
      pharmacodynamics of CHM. Consequently, it is necessary to develop a rational
      approach to connecting the chromatographic fingerprint with effective components
      to assess the internal quality of CHM. For this purpose, a spectrum-effect
      relationship theory was proposed and accepted as a new method for the assessment
      of CHM because of its potential use to screen effective components from CHM. In
      this paper, we systematically reviewed the application of the spectrum-effect
      relationship theory in the research of CHM, including research mentality,
      different chromatographic analysis techniques, data processing technologies, and
      structure determination. 

PMID- 27025365
TI  - A novel arctigenin-containing latex glove prevents latex allergy by inhibiting
      type I/IV allergic reactions.
AB  - The present study aimed at developing a natural compound with anti-allergic
      effect and stability under latex glove manufacturing conditions and investigating
      whether its anti-allergic effect is maintained after its addition into the latex.
      The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse
      primary spleen lymphocytes were determined using MTT assay. The compounds
      included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin,
      arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for
      the in vitro anti-type I/IV allergy screening; in this process beta
      hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN
      gamma and IL-2 released from mouse primary spleen lymphocytes were taken as
      screening indices. The physical stability of eight natural compounds and the
      dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic
      screening and the stability evaluation, were detected by HPLC. The in vivo
      pharmacodynamic confirmation of arctigenin and final latex product was evaluated
      with a passive cutaneous anaphylaxis (PCA) model and an allergen-specific skin
      response model. Nine natural compounds showed minor growth inhibition on RBL-2H3
      cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best
      anti-type I and IV allergic effects among the natural compounds based on the in
      vitro pharmacodynamic screening. Arctigenin and catechin had the best physical
      stability under different manufacturing conditions. Arctigenin was the selected
      for further evaluation and proven to have anti-type I and IV allergic effects in
      vivo in a dose-dependent manner. The final product of the arctigenin-containing
      latex glove had anti-type I and IV allergic effects in vivo which were mainly
      attributed to arctigenin as proved from the dissolubility results. Arctigenin
      showed anti-type I and IV allergic effects in vitro and in vivo, with a good
      stability under latex glove manufacturing conditions, and a persistent anti
      allergic effect after being added into the latex to prevent latex allergy. 

PMID- 27025366
TI  - In vitro antiproliferative and apoptosis-inducing activities of crude ethyle
      alcohole extract of Quercus brantii L. acorn and subsequent fractions.
AB  - Cancer cell resistance to widely used chemotherapeutic agents is gradually
      developed. Natural products, mainly isolated from medicinal plants, have been
      considered as valuable sources for herbal anticancer drugs. The present study
      aimed to evaluate in vitro antiproliferative and apoptosis-inducing activities of
      crude ethyle alcohole extract and four fractions of Q. brantii acorn. Crude
      ethyle alcohole extract of Q. brantii acorn was prepared and subjected to
      fractionation with different polarity. Subsequently, the extract and the
      fractions wereevaluated for their in vitro antiproliferative activity in two
      cancerous (Hela and AGS) and one normal (HDFs) cell lines using MTT [3-(4, 5
      dimethylthiazol-2ol) 2, 5 diphenyltetrazoliumbromide] assay. To determine whether
      the cytotoxicity of these compounds involved the induction of apoptosis, Hela
      cells were treated with IC50 concentrations of test compounds, stained with both
      propidium iodide (PI) and Annexin V-fluorescein isothiocyanate (FITC), and
      analyzed by flow cytometry. In vitro cytotoxicity assay showed that the cell
      viability was significantly reduced in a dose-dependent manner following
      treatment with crude ethyle alcohole extract and Cholophorm and n-Butanol
      fractions. Based on the probit regression model, antiproliferative activities of
      crude ethyle alcohole extract, Cholophorm fraction, and n-Butanol fraction on
      Hela and AGS cells and HDFs cells were significantly different (P < 0.001). The
      results of flow cytometric analysis showed that crude ethyle alcohole extract and
      two fractions of Q. brantii acorn induced early apoptotic cell death. These
      findings suggest that crude ethyle alcohole extract and Cholophorm and n-Butanol
      fractions of Q. brantii acorn suppress the proliferation of cancer cells through
      induction of early apoptosis. 

PMID- 27025367
TI  - Marsdenia tenacissima extract suppresses A549 cell migration through regulation
      of CCR5-CCL5 axis, Rho C, and phosphorylated FAK.
AB  - Marsdenia tenacissima, a traditional Chinese medicine, is long been used to treat
      various diseases including asthma, cancer, trachitis, tonsillitis, pharyngitis,
      cystitis, and pneumonia. Although Marsdenia tenacissima has been demonstrated to
      have strong anti-tumor effects against primary tumors, its effect on cancer
      metastasis remains to be defined, and the molecular mechanism underlying the anti
      metastatic effect is unknown. In the present study, we investigated the effects
      of XAP (an extract of Marsdenia tenacissima) on A549 lung cancer cell migration
      and explored the role of CCR5-CCL5 axis in the anti-metastatic effects of XAP.
      Our resutls showed that XAP inhibited A549 lung cancer cell migration and
      invasion in a dose-dependent manner. The protein levels of CCR5, but not CCR9 and
      CXCR4, were decreased by XAP. The secretion of CCL5, the ligand of CCR5, was
      reduced by XAP. XAP down-regulated Rho C expression and FAK phosphorylation. In
      conclusion, XAP inhibited A549 cell migration and invasion through down
      regulation of CCR5-CCL5 axis, Rho C, and FAK. 

PMID- 27025368
TI  - Urine metabonomic study for blood-replenishing mechanism of Angelica sinensis in
      a blood-deficient mouse model.
AB  - This study aimed at determining the effects of Angelica sinensis (AS) on urinary
      metabolites in blood deficiency mice and exploring its replenishing blood
      mechanism. Gas chromatography-mass spectrometry (GC-MS) was applied to detect
      metabolites in the urine samples in different collection periods. Principal
      component analysis (PCA) and orthogonal partial least squares discriminant
      analysis (OPLS-DA) were used to investigate the differences in metabolic profiles
      among control group (CG), blood deficiency model group (MG), AS groups, and Colla
      Corii Asini group (CCAG). The potential biomarkers were identified based on the
      variable importance in the projection (VIP), T-test, and National Institute of
      Standards and Technology (NIST) and mass spectra library. The metabolites were
      analyzed using metabolomics pathway analysis (MetPA) to build the metabolic
      pathways. Our results indicated that, on the seventh day, the levels of glucose,
      lactic acid, pyruvic acid, alanine, acetoacetic acid, and citric acid changed
      significantly in blood deficiency mice. However, these metabolic deviations came
      to closer to normal levels after AS intervention. The reversing blood-deficiency
      mechanism of AS might involve regulating synthesis and degradation of ketone
      bodies, Pyruvate metabolism, TCA cycle, and Glycolysis/Gluconeogenesis. In
      conclusion, metabonomics is a robust and promising means for the identification
      of biomarkers and elucidation of the mechanisms of a disease, thereby
      highlighting its importance in drug discovery. 

PMID- 27025369
TI  - Transformation of trollioside and isoquercetin by human intestinal flora in
      vitro.
AB  - The present study was designed to determine the intestinal bacterial metabolites
      of trollioside and isoquercetin and their antibacterial activities. A systematic
      in vitro biotransformation investigation on trollioside and isoquercetin,
      including metabolite identification, metabolic pathway deduction, and time
      course, was accomplished using a human intestinal bacterial model. The
      metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial
      activities of trollioside, isoquercetin, and their metabolites were evaluated
      using the broth microdilution method with berberine as a positive control, and
      their potency was measured as minimal inhibitory concentration (MIC). Our results
      indicated that trollioside and isoquercetin were metabolized by human intestinal
      flora through O-deglycosylation, yielding aglycones proglobeflowery acid and
      quercetin, respectively The antibacterial activities of both metabolites were
      more potent than that of their parent compounds. In conclusion, trollioside and
      isoquercetin are totally and rapidly transformed by human intestinal bacteria in
      vitro and the transformation favors the improvement of the antibacterial
      activities of the parent compounds. 

PMID- 27025370
TI  - Two novel resin glycosides isolated from Ipomoea cairica with alpha-glucosidase
      inhibitory activity.
AB  - In the present study, two new compounds from Ipomoea cairica were identified and
      demonstrated to have alpha-glucosidase inhibitory activity. They were isolated by
      column chromatography on silica gel and sephadex LH-20 and finally purified by
      prep-HPLC, with their structures being elucidated by spectroscopic methods, such
      as 1D- and 2D-NMR and HR-TOF-MS, and chemical methods. Compounds 1 and 2, named
      cairicoside A and cairicoside B, were evaluated for alpha-glucosidase inhibitory
      activity by the MTT method, with the IC50 values being 25.3 +/- 1.6 and 28.5 +/-
      3.3 MUmol.L(-1), respectively. 

PMID- 27025371
TI  - Two new ortho benzoquinones from Uncaria rhynchophylla.
AB  - The present study was designed to determine the chemical constituents of the
      stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated
      and purified from CH2Cl2 fraction by chromatography. Their structures were
      elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT
      method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone
      (1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone (2), together with a known
      compound isorhynchophyllic acid (3) were isolated from U. rhynchophylla. These
      compounds were evaluated for their cytotoxicity against cancer cells A549, HepG2
      and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak
      antiproliferative activities on A549, HepG2 and A2780 cells. Compound 3
      significantly inhibited the proliferation of A549, HepG2 and A2780 cells with
      IC50 values being 5.8, 12.8 and 11.8 umol.L(-1), respectively. 

PMID- 27025372
TI  - Sources of varieties and quality of circular Fructus Ligustri Lucidi.
AB  - This study aimed to trace sources and quantitatively analyze the specnuezhenide
      content of circular Fructus Ligustri Lucidi for clinical use. Different
      specifications of Fructus Ligustri Lucidi were identified using DNA barcoding
      technology and the specnuezhenide content was analyzed by High Performance Liquid
      Chromatography (HPLC). The ITS sequence of circular Fructus Ligustri Lucidi was
      identical to that of standard privet, which was determined through botanical
      identification. ITS sequence similarity between circular Fructus Ligustri Lucidi
      and Fructus Ligustri Lucidi which was registered in NCBI ranged from 99.5% to
      100%. The sequences of circular and other Fructus Ligustri Lucidi were clustered
      in a Neighbor-Joining tree with bootstrap value of 95, and these sequences could
      be distinguished from adulterants. Conforming to pharmacopoeia standard, the
      average specnuezhenide content of circular Fructus Ligustri Lucidi was higher
      than that of chicken waist Fructus Ligustri Lucidi. Circular Fructus Ligustri
      Lucidi derived from Ligustrum lucidum Ait. and the specnuezhenide content was
      higher in circular Fructus Ligustri Lucidi than that in chicken waist Fructus
      Ligustri Lucidi. 

PMID- 27025373
TI  - Sensitivities of Biopsy Sites in the Endoscopic Evaluation of Graft-Versus-Host
      Disease: Retrospective Review from a Tertiary Center.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a complication of hematopoietic
      stem cell transplantation that frequently affects the gastrointestinal (GI)
      tract. The best biopsy sites to establish the diagnosis have not been clearly
      established. AIMS: To determine the best sites for obtaining biopsies in
      evaluating GI GVHD. METHODS: All cases of biopsy-proven GI GVHD (GVHD+) were
      isolated from a pathology database over a 2-year period at a single tertiary
      center (n = 46). Demographic, clinical, and endoscopic data were extracted. For
      comparison, 46 consecutive GVHD-negative cases (GVHD-) were obtained.
      Sensitivities in diagnosing GVHD in the upper and lower GI tract were calculated.
      RESULTS: In the GVHD- group, they were commonly investigated with an
      esophagogastroduodenoscopy (EGD) (60 vs. 22 % in the GVHD+ group, p < 0.01),
      while a colonoscopy (CLN) was commonly performed in the GVHD+ group (33 vs. 12 %,
      p = 0.02). Among the GVHD + patients, for EGDs, the sensitivity was highest for
      duodenal biopsies at 89 %. For flexible sigmoidoscopies (FSs) and CLNs, the
      sensitivities among all sites were similar (85 % agreement, kappa 0.58, p =
      0.01). There were no cases in which GVHD was diagnosed in the right side of the
      colon without a positive biopsy in the left side of the colon. CONCLUSIONS: In
      this cohort of GI GVHD patients, duodenum biopsies produced the highest yield in
      diagnosing GVHD when compared to other sites of the upper GI tract. Sensitivities
      were similar among all sites on lower endoscopies, suggesting that a FS is
      sufficient for diagnosing GVHD in suspected patients with diarrhea.

PMID- 27025374
TI  - Adverse effects of nephrectomy.

PMID- 27025375
TI  - Intergenerational transmission of historical memories and social-distance
      attitudes in post-war second-generation Croatians.
AB  - Intergenerational transmission of memory is a process by which biographical
      knowledge contributes to the construction of collective memory (representation of
      a shared past). We investigated the intergenerational transmission of war-related
      memories and social-distance attitudes in second-generation post-war Croatians.
      We compared 2 groups of young adults from (1) Eastern Croatia (extensively
      affected by the war) and (2) Western Croatia (affected relatively less by the
      war). Participants were asked to (a) recall the 10 most important events that
      occurred in one of their parents' lives, (b) estimate the calendar years of each,
      and (c) provide scale ratings on them. Additionally, (d) all participants
      completed a modified Bogardus Social Distance scale, as well as an (e) War Events
      Checklist for their parents' lives. There were several findings. First,
      approximately two-thirds of Eastern Croatians and one-half of Western Croatians
      reported war-related events from their parents' lives. Second, war-related
      memories impacted the second-generation's identity to a greater extent than did
      non-war-related memories; this effect was significantly greater in Eastern
      Croatians than in Western Croatians. Third, war-related events displayed markedly
      different mnemonic characteristics than non-war-related events. Fourth, the
      temporal distribution of events surrounding the war produced an upheaval bump,
      suggesting major transitions (e.g., war) contribute to the way collective memory
      is formed. And, finally, outright social ostracism and aggression toward out
      groups were rarely expressed, independent of region. Nonetheless, social-distance
      scores were notably higher in Eastern Croatia than in Western Croatia.

PMID- 27025376
TI  - Synergistic inhibitory effect of cetuximab and tectochrysin on human colon cancer
      cell growth via inhibition of EGFR signal.
AB  - The purpose of this study was to evaluate the enhancing potency of tectochrysin,
      a flavonoid isolated from Alpinia oxyphylla Miquel by combining cetuximab, an
      anti-EGFR monoclonal antibody, on human colon cancer cell growth through further
      inhibition of EGFR pathway. HCT116 and SW480 colon cancer cells were treated with
      cetuximab (30 MUg/mL, 1/10 of IC50), tectochrysin (5 MUg/mL, 1/3 of IC50), or the
      combination of both agents. The growth inhibitory effect was examined using the
      MTT assay while apoptotic cell death was performed using TUNEL staining assays.
      The DNA binding activity of NF-kappa B and AP-1 was investigated by
      electrophoretic mobility shift assay. Protein expression was determined by
      Western blot. Cell proliferation was significantly inhibited by the combination
      of cetuximab and tectochrysin than treatment with cetuximab or tectochrysin alone
      (combination index: 0.572 and 0.533, respectively). Combination treatment of
      cells with cetuximab and tectochrysin significantly reduced the expressions of p
      EGFR and COX-2 in both cell lines. Combination treatment also significantly
      inhibited activities of NF-kB and AP-1 compared to the single agent treatment.
      Our results indicate that combined therapy with lower concentration of cetuximab
      and tectochrysin could significantly enhance the cancer cell growth inhibitory
      effect through the inhibition of EGFR signaling. 

PMID- 27025377
TI  - Prediction of hybrid performance in maize with a ridge regression model employed
      to DNA markers and mRNA transcription profiles.
AB  - BACKGROUND: Ridge regression models can be used for predicting heterosis and
      hybrid performance. Their application to mRNA transcription profiles has not yet
      been investigated. Our objective was to compare the prediction accuracy of models
      employing mRNA transcription profiles with that of models employing genome-wide
      markers using a data set of 98 maize hybrids from a breeding program. RESULTS: We
      predicted hybrid performance and mid-parent heterosis for grain yield and grain
      dry matter content and employed cross validation to assess the prediction
      accuracy. Prediction with a ridge regression model using random effects for mRNA
      transcription profiles resulted in similar prediction accuracies than employing
      the model to DNA markers. For hybrids, of which none of the parental inbred lines
      was part of the training set, the ridge regression model did not reach the
      prediction accuracy that was obtained with a model using transcriptome-based
      distances. CONCLUSION: We conclude that mRNA transcription profiles are a
      promising alternative to DNA markers for hybrid prediction, but further studies
      with larger data sets are required to investigate the superiority of alternative
      prediction models.

PMID- 27025378
TI  - Effective Rheological Properties in Semi-dilute Bacterial Suspensions.
AB  - Interactions between swimming bacteria have led to remarkable experimentally
      observable macroscopic properties such as the reduction in the effective
      viscosity, enhanced mixing, and diffusion. In this work, we study an individual
      based model for a suspension of interacting point dipoles representing bacteria
      in order to gain greater insight into the physical mechanisms responsible for the
      drastic reduction in the effective viscosity. In particular, asymptotic analysis
      is carried out on the corresponding kinetic equation governing the distribution
      of bacteria orientations. This allows one to derive an explicit asymptotic
      formula for the effective viscosity of the bacterial suspension in the limit of
      bacterium non-sphericity. The results show good qualitative agreement with
      numerical simulations and previous experimental observations. Finally, we justify
      our approach by proving existence, uniqueness, and regularity properties for this
      kinetic PDE model. 

PMID- 27025379
TI  - Spatial Organization of Cell Wall-Anchored Proteins at the Surface of Gram
      Positive Bacteria.
AB  - Bacterial surface proteins constitute an amazing repertoire of molecules with
      important functions such as adherence, invasion, signalling and interaction with
      the host immune system or environment. In Gram-positive bacteria, many surface
      proteins of the "LPxTG" family are anchored to the peptidoglycan (PG) by an
      enzyme named sortase. While this anchoring mechanism has been clearly deciphered,
      less is known about the spatial organization of cell wall-anchored proteins in
      the bacterial envelope. Here, we review the question of the precise spatial and
      temporal positioning of LPxTG proteins in subcellular domains in spherical and
      ellipsoid bacteria (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus
      agalactiae and Enterococcus faecalis) and in the rod-shaped bacterium Listeria
      monocytogenes. Deposition at specific sites of the cell wall is a dynamic process
      tightly connected to cell division, secretion, cell morphogenesis and levels of
      gene expression. Studying spatial occupancy of these cell wall-anchored proteins
      not only provides information on PG dynamics in responses to environmental
      changes, but also suggests that pathogenic bacteria control the distribution of
      virulence factors at specific sites of the surface, including pole, septa or
      lateral sites, during the infectious process.

PMID- 27025380
TI  - Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus.
AB  - Staphylococcus aureus is an important human pathogen, responsible for infections
      in the community and the healthcare setting. Although much of the attention is
      focused on the methicillin-resistant "variant" MRSA, the methicillin-susceptible
      counterpart (MSSA) remains a prime species in infections. The epidemiology of S.
      aureus, especially of MRSA, showed a rapid evolution in the last years. After
      representing a typical nosocomial multidrug-resistant pathogen, MRSA has recently
      emerged in the community and among farmed animals thanks to its ability to evolve
      and adapt to different settings. Global surveillance has shown that MRSA
      represents a problem in all continents and countries where studies have been
      carried out, determining an increase in mortality and the need to use last
      resource expensive antibiotics. S. aureus can easily acquire resistance to
      antibiotics and MRSA is characteristically multidrug resistant. Resistance to
      vancomycin, the principal anti-MRSA antibiotic is rare, although isolates with
      decreased susceptibility are recovered in many areas. Resistance to the more
      recently introduced antibiotics, linezolid and daptomycin, has emerged; however,
      they remain substantially active against the large majority of MSSA and MRSA.
      Newer antistaphylococcal drugs have been developed, but since their clinical use
      has been very limited so far, little is known about the emergence of resistance.
      Molecular typing techniques have allowed to identify the major successful clones
      and lineages of MSSA and MRSA, including high-risk clones, and to trace their
      diffusion. In the face of a continuously evolving scenario, this review depicts
      the most common clones circulating in different geographical areas and in
      different settings at present. Since the evolution of S. aureus will continue, it
      is important to maintain the attention on the epidemiology of S. aureus in the
      future with a global view.

PMID- 27025382
TI  - An analysis on the suppression of NO and PGE2 by diphenylheptane A and its effect
      on glycerophospholipids of lipopolysaccharide-induced RAW264.7 cells with
      UPLC/ESI-QTOF-MS.
AB  - Diarylheptanoid A, 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3
      heptanone, is a naturally occurring phytochemical ingredient isolated from the
      rhizome of Alpinia officinarum. In order to confirm the anti-inflammatory
      activity of diphenylheptane A, we investigated its effects on lipopolysaccharide
      (LPS)-induced pro-inflammatory mediators, such as nitric oxide (NO),
      prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), and tumor necrosis factor
      alpha (TNF-alpha), as well as upstream genes, including the inducible nitric
      oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappaB (NF
      kappaB) p65, p38 mitogen-activated protein kinase (MAPK), and extracellular
      signal-regulated kinase 1/2 (ERK1/2). Our results have proved the anti
      inflammatory property of diphenylheptane A. Based on this finding, an LPS-induced
      RAW264.7 cell inflammatory model was introduced to evaluate the anti-inflammatory
      activity associated with glycerophospholipid (GPL) metabolism regulated by
      diphenylheptane A. We applied ultra-performance liquid
      chromatography/electrospray ionization-quadruple time of flight-mass spectrometry
      (UPLC/ESI-QTOF-MS) to the metabolic profiling of GPL synthesis in LPS-stimulated
      macrophages with the aim of identifying differentially synthesized GPL
      metabolites. Sixteen GPL metabolites, whose changes were restored to normal level
      after diphenylheptane A treatment, were further screened to be considered as
      useful biomarkers of inflammation. Overall, our study revealed for the first time
      that diphenylheptane A reestablished the production of 16 plasma membrane GPLs to
      basal level in LPS-activated RAW264.7 cells, suggesting the potential therapeutic
      property of phytochemical compounds against inflammatory diseases.

PMID- 27025381
TI  - Double ophthalmic arteries arising from the internal carotid artery: a case
      report of a hidden second ophthalmic artery.
AB  - A case of double ophthalmic arteries arising from the internal carotid artery
      with unique features is reported. This case was discovered following in the
      course of time the progress of a thrombosis of the anterior cavernous sinus
      associated with a low-flow direct arteriovenous fistula of the superior
      ophthalmic vein. At different time points, the same patient underwent four
      angiographic studies and one computerized tomography with contrast medium.
      Angiographies showed that the double internal carotid artery origin of the
      ophthalmic artery was detectable only within a short range of time. To the best
      of our knowledge, this case is unique as it demonstrates that a second ophthalmic
      artery may lie hidden, showing itself only under particular hemodynamic
      requirements.

PMID- 27025383
TI  - [Autoimmune pancreatitis: An update].
AB  - CLINICAL/METHODICAL ISSUE: Autoimmune pancreatitis (AIP) is a rare disease, the
      pathophysiological understanding of which has been greatly improved over the last
      years. The most common form, type 1 AIP belongs to the IgG4-related diseases and
      must be distinguished from type 2 AIP, which is a much rarer entity associated
      with chronic inflammatory bowel disease. Clinically, there is an overlap with
      pancreatic cancer. Imaging and further criteria, such as serological and
      histological parameters are utilized for a differentiation between both entities
      in order to select the appropriate therapy and to avoid the small but ultimately
      unnecessary number of pancreatectomies. PERFORMANCE: The diagnostics of AIP are
      complex, whereby the consensus criteria of the International Association of
      Pancreatology have become accepted as the parameters for discrimination. These
      encompass five cardinal criteria and one therapeutic criterion. By applying these
      criteria AIP can be diagnosed with a sensitivity of 84.9%, a specificity of 100%
      and an accuracy of 93.8%. ACHIEVEMENTS: The diagnosis of AIP is accomplished by
      applying several parameters of which two relate to imaging. As for the routine
      diagnostics of the pancreas these are ultrasound, computed tomography (CT) and
      magnetic resonance imaging (MRI). Important for the differential diagnosis is the
      exclusion of signs of local and remote tumor spread for which CT and MRI are
      established. The essential diagnostic parameter of histology necessitates
      sufficient sample material, which cannot usually be acquired by a fine needle
      biopsy. CT or MRI are the reference standard methods for identification of the
      optimal puncture site and imaging-assisted (TruCut) biopsy. PRACTICAL
      RECOMMENDATIONS: In patients presenting with unspecific upper abdominal pain,
      painless jaundice combined with the suspicion of a pancreatic malignancy in
      imaging but a mismatch of secondary signs of malignancy, AIP should also be
      considered as a differential diagnosis. As the diagnosis of AIP only partially
      relies on imaging radiologists also have to be aware of the clinical, serological
      and histological parameters for AIP in order to guide clinicians towards the
      correct diagnosis. Only in this way can the highly efficient steroid therapy be
      initiated and otherwise possibly severe forms of therapy be avoided.

PMID- 27025384
TI  - [Occipitocervical junction: Aanatomy, craniometry and pathology].
AB  - The occipitocervical junction comprises of the occiput condyles, the atlas, and
      the axis. The radiological evaluation of this region is supported by craniometric
      measurement methods which are based on predefined anatomical landmarks. The main
      pathologies of the occipitocervical junction are traumatic injuries, congenital
      anomalies or normal variants, infections, arthropathies, and tumors. In this
      article, the anatomy of the occipitocervical junction as well as the most
      important craniometric measurement methods are explained. Moreover various
      pathologies and similar appearing normal variants are presented. 

PMID- 27025385
TI  - Latina Birth Outcomes in California: Not so Paradoxical.
AB  - Objectives To investigate Latina-White differences in birth outcomes in
      California from 2003 to 2010, looking for evidence of the often-cited "Latina
      paradox" and assessing the possible role of socioeconomic factors in observed
      differences. MethodsUsing statewide-representative data from the California
      Maternal and Infant Health Assessment, an annual population-based postpartum
      survey, we compared rates of preterm birth (PTB) and low birth weight (LBW) in
      five groups: U.S.-born non-Latina Whites ("Whites"), U.S.-born Mexican-Americans,
      U.S.-born non-Mexican Latinas, Mexican immigrants, and non-Mexican Latina
      immigrants. Logistic regression models examined the relative likelihood of PTB
      and LBW for women in each Latina subgroup compared with Whites, before and after
      adjustment for socioeconomic and other covariates. Results In unadjusted
      analyses, women in each Latina subgroup appeared more likely than White women to
      have PTB and LBW, although the increased likelihood of LBW among Mexican
      immigrants was statistically non-significant. After adjustment for less favorable
      socioeconomic characteristics among Latinas compared with Whites, observed
      differences in the estimated likelihoods of PTB or LBW for Latina subgroups
      relative to Whites were attenuated and (with the exception of PTB among U.S.-born
      Mexican Americans) no longer statistically significant. Conclusions We found no
      evidence of a "Latina paradox" in birth outcomes, which some have cited as
      evidence that social disadvantage is not always health-damaging. As observed in
      several previous studies, our findings were non-paradoxical: consistent with
      their socioeconomic disadvantage, Latinas had worse birth outcomes than non
      Latina White women. Policy-makers should not rely on a "Latina paradox" to ensure
      good birth outcomes among socioeconomically disadvantaged Latina women.

PMID- 27025386
TI  - Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted
      Gene Panel Sequencing.
AB  - Inherited peripheral neuropathies (IPN), which are a group of clinically and
      genetically heterogeneous peripheral nerve disorders including Charcot-Marie
      Tooth disease (CMT), exhibit progressive degeneration of muscles in the
      extremities and loss of sensory function. Over 70 genes have been reported as
      genetic causatives and the number is still growing. We prepared a targeted gene
      panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel
      was designed to detect mutations in 73 genes reported to be genetic causes of IPN
      or related peripheral neuropathies, and to detect duplication of the chromosome
      17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115
      samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely
      pathogenic mutations in eight genes from 25 patients (17 families). Of them,
      eight mutations were unreported variants. Of particular interest, this study
      revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In
      addition, the effectiveness of the detection of CMT1A was confirmed by comparing
      five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed
      a gene panel for one step genetic diagnosis of IPN. It seems that its time- and
      cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms,
      and it could be applied as a genetic diagnostic system for inherited peripheral
      neuropathies. 

PMID- 27025387
TI  - A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced
      Osteoblast Differentiation In Vitro.
AB  - Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in
      clinical phase I/II/III development for the treatment of various types of
      cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic
      profile. Although dovitinib can bind several kinases at nanomolar concentrations,
      there are no reports relating to osteoporosis or osteoblast differentiation.
      Herein, we investigated the effect of dovitinib on human recombinant bone
      morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell
      culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP)
      induction, which is a representative marker of osteoblast differentiation.
      Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the
      nucleus and phosphorylation of mitogen-activated protein kinases, including
      ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN
      increased with dovitinib treatment. Our results suggest that dovitinib has a
      potent stimulating effect on BMP-2-induced osteoblast differentiation and this
      existing drug has potential for repositioning in the treatment of bone-related
      disorders. 

PMID- 27025388
TI  - Genes Frequently Coexpressed with Hoxc8 Provide Insight into the Discovery of
      Target Genes.
AB  - Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated
      regulatory networks underlying its roles during development. However,
      identification of these genes remains difficult due to intrinsic factors of
      Hoxc8, such as low DNA binding specificity, context-dependent regulation, and
      unknown cofactors. Therefore, as an alternative, the present study attempted to
      test whether the roles of Hoxc8 could be inferred by simply analyzing genes
      frequently coexpressed with Hoxc8, and whether these genes include putative
      target genes. Using archived gene expression datasets in which Hoxc8 was
      differentially expressed, we identified a total of 567 genes that were positively
      coexpressed with Hoxc8 in at least four out of eight datasets. Among these, 23
      genes were coexpressed in six datasets. Gene sets associated with extracellular
      matrix and cell adhesion were most significantly enriched, followed by gene sets
      for skeletal system development, morphogenesis, cell motility, and
      transcriptional regulation. In particular, transcriptional regulators, including
      paralogs of Hoxc8, known Hox co-factors, and transcriptional remodeling factors
      were enriched. We randomly selected Adam19, Ptpn13, Prkd1, Tgfbi, and Aldh1a3,
      and validated their coexpression in mouse embryonic tissues and cell lines
      following TGF-beta2 treatment or ectopic Hoxc8 expression. Except for Aldh1a3,
      all genes showed concordant expression with that of Hoxc8, suggesting that the
      coexpressed genes might include direct or indirect target genes. Collectively, we
      suggest that the coexpressed genes provide a resource for constructing Hoxc8
      mediated regulatory networks. 

PMID- 27025389
TI  - Arginine Supplementation Recovered the IFN-gamma-Mediated Decrease in Milk
      Protein and Fat Synthesis by Inhibiting the GCN2/eIF2alpha Pathway, Which Induces
      Autophagy in Primary Bovine Mammary Epithelial Cells.
AB  - During the lactation cycle of the bovine mammary gland, autophagy is induced in
      bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival
      mechanism. Interferon gamma (IFN-gamma) is an important antiproliferative and
      apoptogenic factor that has been shown to induce autophagy in multiple cell lines
      in vitro. However, it remains unclear whether IFN-gamma can induce autophagy and
      whether autophagy affects milk synthesis in BMECs. To understand whether IFN
      gamma affects milk synthesis, we isolated and purified primary BMECs and
      investigated the effect of IFN-gamma on milk synthesis in primary BMECs in vitro.
      The results showed that IFN-gamma significantly inhibits milk synthesis and that
      autophagy was clearly induced in primary BMECs in vitro within 24 h.
      Interestingly, autophagy was observed following IFN-gamma treatment, and the
      inhibition of autophagy can improve milk protein and milk fat synthesis.
      Conversely, upregulation of autophagy decreased milk synthesis. Furthermore,
      mechanistic analysis confirmed that IFN-gamma mediated autophagy by depleting
      arginine and inhibiting the general control nonderepressible-2 kinase
      (GCN2)/eukaryotic initiation factor 2alpha (eIF2alpha) signaling pathway in
      BMECs. Then, it was found that arginine supplementation could attenuate IFN-gamma
      induced autophagy and recover milk synthesis to some extent. These findings may
      not only provide a novel measure for preventing the IFN-gamma-induced decrease in
      milk quality but also a useful therapeutic approach for IFN-gamma-associated
      breast diseases in other animals and humans. 

PMID- 27025390
TI  - A Systematic Analysis of Drosophila Regulatory Peptide Expression in
      Enteroendocrine Cells.
AB  - The digestive system is gaining interest as a major regulator of various
      functions including immune defense, nutrient accumulation, and regulation of
      feeding behavior, aside from its conventional function as a digestive organ. The
      Drosophila midgut epithelium is completely renewed every 1-2 weeks due to
      differentiation of pluripotent intestinal stem cells in the midgut. Intestinal
      stem cells constantly divide and differentiate into enterocytes that secrete
      digestive enzymes and absorb nutrients, or enteroendocrine cells that secrete
      regulatory peptides. Regulatory peptides have important roles in development and
      metabolism, but study has mainly focused on expression and functions in the
      nervous system, and not much is known about the roles in endocrine functions of
      enteroendocrine cells. We systemically examined the expression of 45 regulatory
      peptide genes in the Drosophila midgut, and verified that at least 10 genes are
      expressed in the midgut enteroendocrine cells through RT-PCR, in situ
      hybridization, antisera, and 25 regulatory peptide-GAL transgenes. The Drosophila
      midgut is highly compartmentalized, and individual peptides in enteroendocrine
      cells were observed to express in specific regions of the midgut. We also
      confirmed that some peptides expressed in the same region of the midgut are
      expressed in mutually exclusive enteroendocrine cells. These results indicate
      that the midgut enteroendocrine cells are functionally differentiated into
      different subgroups. Through this study, we have established a basis to study
      regulatory peptide functions in enteroendocrine cells as well as the complex
      organization of enteroendocrine cells in the Drosophila midgut. 

PMID- 27025391
TI  - Erratum to: In situ validation of VEGFR-2 and alpha v beta 3 integrin as targets
      for breast lesion characterization.

PMID- 27025392
TI  - A ferrocene-azobenzene derivative showing unprecedented phase transition and
      better solubility upon UV irradiation.
AB  - The ferrocene-aspartic acid-azobenzene derivative 1 showing an unprecedented
      photoinduced crystal-liquid phase transition at an elevated temperature and
      better solubility in organic solvents has been successfully reported. 

PMID- 27025396
TI  - Transanal endoscopic video-assisted (TEVA) resection of early rectal lesions
      using a SILS port A single center experience.
AB  - represents a safe and complete technique to remove benign lesions of the rectum
      not treatable by endoscopy and malignant rectal lesions at early stage. It is a
      valid alternative to transanal endoscopic microsurgery (TEM), to conventional
      transanal surgery and to transabdominal resection. METHODS: In our operating Unit
      we performed a resection of 8 voluminous adenoma in the rectal ampulla with
      SILSTM-Port. RESULTS: The mean age of the patients was of 51.1 years, the mean
      BMI was 23. There were not intra or post-operative complications nor conversions
      to conventional transanal excision or major resective surgery. The postoperative
      course was normal. The average time of hospitalization was 3 days. CONCLUSIONS:
      TEVA is easier to perform than TEM and does not require a long training and
      specific and expensive material as the TEM does. TEVA might go to replace
      completely TEM. KEY WORDS: Rectal tumours, SILS, TEVA.

PMID- 27025397
TI  - A chemical family-based strategy for uncovering hidden bioactive molecules and
      multicomponent interactions in herbal medicines.
AB  - Two concepts involving natural products were proposed and demonstrated in this
      paper. (1) Natural product libraries (e.g. herbal extract) are not perfect for
      bioactivity screening because of the vast complexity of compound compositions,
      and thus a library reconstruction procedure is necessary before screening. (2)
      The traditional mode of "screening single compound" could be improved to
      "screening single compound, drug combination and multicomponent interaction" due
      to the fact that herbal medicines work by integrative effects of multi-components
      rather than single effective constituents. Based on the two concepts, we
      established a novel strategy aiming to make screening easier and deeper. Using
      thrombin as the model enzyme, we firstly uncovered the minor lead compounds,
      potential drug combinations and multicomponent interactions in an herbal medicine
      of Dan-Qi pair, showing a significant advantage over previous methods. This
      strategy was expected to be a new and promising mode for investigation of herbal
      medicines. 

PMID- 27025398
TI  - Acoustic force mapping in a hybrid acoustic-optical micromanipulation device
      supporting high resolution optical imaging.
AB  - Many applications in the life-sciences demand non-contact manipulation tools for
      forceful but nevertheless delicate handling of various types of sample. Moreover,
      the system should support high-resolution optical imaging. Here we present a
      hybrid acoustic/optical manipulation system which utilizes a transparent
      transducer, making it compatible with high-NA imaging in a microfluidic
      environment. The powerful acoustic trapping within a layered resonator, which is
      suitable for highly parallel particle handling, is complemented by the
      flexibility and selectivity of holographic optical tweezers, with the specimens
      being under high quality optical monitoring at all times. The dual
      acoustic/optical nature of the system lends itself to optically measure the exact
      acoustic force map, by means of direct force measurements on an optically trapped
      particle. For applications with (ultra-)high demand on the precision of the force
      measurements, the position of the objective used for the high-NA imaging may have
      significant influence on the acoustic force map in the probe chamber. We have
      characterized this influence experimentally and the findings were confirmed by
      model simulations. We show that it is possible to design the chamber and to
      choose the operating point in such a way as to avoid perturbations due to the
      objective lens. Moreover, we found that measuring the electrical impedance of the
      transducer provides an easy indicator for the acoustic resonances. 

PMID- 27025399
TI  - Increasing Antiretroviral Adherence for HIV-Positive African Americans (Project
      Rise): A Treatment Education Intervention Protocol.
AB  - BACKGROUND: HIV-positive African Americans have been shown to have lower
      adherence to antiretroviral therapy (ART) than those of other races/ethnicities,
      yet adherence interventions have rarely been tailored to the needs of this
      population. OBJECTIVE: We developed and will evaluate a treatment education
      adherence intervention (called Rise) that was culturally adapted to address the
      needs of African Americans living with HIV. METHODS: This randomized controlled
      trial will examine the effects of the Rise intervention on ART adherence and HIV
      viral load. African Americans on ART who report adherence problems will be
      recruited from the community and randomly assigned to receive the intervention or
      usual care for 6 months. The intervention consists of 6-10 individual counseling
      sessions, with more sessions provided to those who demonstrate lower adherence.
      Primary outcomes include adherence as monitored continuously with Medication
      Event Monitoring Systems (MEMS) caps, and viral load data received from the
      participant's medical provider. Survey assessments will be administered at
      baseline and month 6. RESULTS: The trial is ongoing. CONCLUSIONS: If effective,
      the Rise intervention will provide community-based organizations with an
      intervention tailored to address the needs of African Americans for promoting
      optimal ART adherence and HIV clinical outcomes. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01350544; https://clinicaltrials.gov/ct2/show/NCT01350544
      (Archived by WebCite at http://www.webcitation.org/6fjqqnmn0).

PMID- 27025400
TI  - Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of
      neural stem cell survival and differentiation after ischaemia.
AB  - Stroke is one of the leading causes of death and disability worldwide. However,
      current therapies only reach a small percentage of patients and may cause serious
      side effects. We propose the therapeutic use of retinoic acid-loaded
      nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by
      creating a favourable pro-angiogenic environment that enhances neurogenesis and
      neuronal restitution. Our data showed that RA-NP enhanced endothelial cell
      proliferation and tubule network formation and protected against ischaemia
      induced death. To evaluate the effect of RA-NP on vascular regulation of neural
      stem cell (NSC) survival and differentiation, endothelial cell-conditioned media
      (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death
      and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells
      decreased cell death, increased proliferation and neuronal differentiation. In
      parallel, human endothelial progenitor cells (hEPC), which are part of the
      endogenous repair response to vascular injury, were collected from ischaemic
      stroke patients. hEPC treated with RA-NP had significantly higher proliferation,
      which further highlights the therapeutic potential of this formulation. To
      conclude, RA-NP protected endothelial cells from ischaemic death and stimulated
      the release of pro-survival, proliferation-stimulating factors and
      differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient
      than free RA and to enhance hEPC proliferation. These data serve as a stepping
      stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders
      and neurodegenerative diseases with compromised vasculature. 

PMID- 27025401
TI  - Enhanced cell survival and paracrine effects of mesenchymal stem cells
      overexpressing hepatocyte growth factor promote cardioprotection in myocardial
      infarction.
AB  - Poor cell survival post transplantation compromises the therapeutic benefits of
      mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth
      factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and
      anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs
      overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord
      derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was
      detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic
      condition was harvested and its protective effect on neonatal cardiomyocytes
      (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were
      transplanted into the peri-infarct region in mice following MI and heart function
      assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic
      conditions was markedly decreased compared with that of UC-MSCs. NCMs treated
      with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in
      response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs
      hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced
      ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed
      higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of
      HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI.
      Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less
      cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of
      cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based
      therapy in cardiovascular disease.

PMID- 27025402
TI  - Spectral distribution of local field potential responses to electrical
      stimulation of the retina.
AB  - OBJECTIVE: Different frequency bands of the local field potential (LFP) have been
      shown to reflect neuronal activity occurring at varying cortical scales. As such,
      recordings of the LFP may offer a novel way to test the efficacy of neural
      prostheses and allow improvement of stimulation strategies via neural feedback.
      Here we use LFP measurements from visual cortex to characterize neural responses
      to electrical stimulation of the retina. We aim to show that the LFP is a viable
      signal that contains sufficient information to optimize the performance of
      sensory neural prostheses. APPROACH: Clinically relevant electrode arrays were
      implanted in the suprachoroidal space of one eye in four felines. LFPs were
      simultaneously recorded in response to stimulation of individual electrodes using
      penetrating microelectrode arrays from the visual cortex. The frequency response
      of each electrode was extracted using multi-taper spectral analysis and the
      uniqueness of the responses was determined via a linear decoder. MAIN RESULTS: We
      found that cortical LFPs are reliably modulated by electrical stimulation of the
      retina and that the responses are spatially localized. We further characterized
      the spectral distribution of responses, with maximum information being contained
      in the low and high gamma bands. Finally, we found that LFP responses are unique
      to a large range of stimulus parameters (~40) with a maximum conveyable
      information rate of 6.1 bits. SIGNIFICANCE: These results show that the LFP can
      be used to validate responses to electrical stimulation of the retina and we
      provide the first steps towards using these responses to provide more efficacious
      stimulation strategies.

PMID- 27025403
TI  - Development and Acceptability of a Co-Produced Online Intervention to Prevent
      Alcohol Misuse in Adolescents: A Think Aloud Study.
AB  - BACKGROUND: The prototype willingness model (PWM) may offer an appropriate basis
      for explaining and preventing adolescent alcohol misuse. An intervention was
      developed using a co-production approach, and consisted of an online quiz
      featuring 10 questions linked to the PWM. OBJECTIVE: This study sought to
      determine the acceptability and relevance of the intervention content to young
      people, to incorporate their feedback into a final version. METHODS: A
      qualitative think aloud study with follow-up semistructured interviews was
      undertaken with 16 young people aged 11-15 (50%). Transcripts were analyzed using
      thematic analysis. RESULTS: The following 3 main themes relating the
      acceptability of the intervention were identified: "challenging expectations of
      alcohol education"; "motivations for drinking or not drinking," and "the
      inevitability of drinking." Participants found the intervention appealing because
      it was counter to their expectations. The content appeared to reflect their
      experiences of social pressure and drinking encounters. There was evidence that a
      focus on drinker/nondrinker prototypes was too narrow and that because
      adolescents perceived drinking as inevitable, it would be challenging to enact
      any plans to resist pressure to drink. CONCLUSIONS: An online intervention based
      on the PWM has the potential to engage and interest adolescents. A wide range of
      alcohol prototypes should be targeted and a focus on short-term harms should
      ensure that the intervention is credible to young people.

PMID- 27025404
TI  - Acceptance of New Technology: A Usability Test of a Computerized Adaptive Test
      for Fatigue in Rheumatoid Arthritis.
AB  - BACKGROUND: Little is known about the acceptance and usability of computerized
      adaptive tests (CATs) among patients with rheumatoid arthritis (RA). The main
      difference between completing a CAT and a traditional questionnaire concerns item
      presentation. CATs only provide one item at a time on the screen, and skipping
      forward or backward to review and change already given answers is often not
      possible. OBJECTIVE: The objective of this study was to examine how patients with
      RA experience a Web-based CAT for fatigue. METHODS: In individual sessions,
      participants filled in the CAT while thinking aloud, and were subsequently
      interviewed about their experience with the new instrument. The technology
      acceptance model (TAM) was used to structure the results. RESULTS: The
      participants were 15 patients with RA. They perceived the CAT as clear, brief,
      and easy to use. They were positive about answering one question per screen, the
      changing response options, layout, progress bar, and item number. There were 40%
      (6/15) of the participants that also mentioned that they experienced the
      completion of the CAT as useful and pleasant, and liked the adaptive test
      mechanism. However, some participants noted that not all items were applicable to
      everybody, and that the wordings of questions within the severity dimension were
      often similar. CONCLUSIONS: Participants perceived the "CAT Fatigue RA" as easy
      to use, and also its usefulness was expressed. A 2.0 version has been improved
      according to the participants' comments, and is currently being used in a
      validation study before it will be implemented in daily clinical practice. Our
      results give a first indication that CAT methodology may outperform traditional
      questionnaires not merely on measurement precision, but also on usability and
      acceptance valuation.

PMID- 27025405
TI  - On the dynamics of Liesegang-type pattern formation in a gaseous system.
AB  - Liesegang pattern formations are widely spread in nature. In spite of a
      comparably simple experimental setup under laboratory conditions, a variety of
      spatio-temporal structures may arise. Presumably because of easier control of the
      experimental conditions, Liesegang pattern formation was mainly studied in gel
      systems during more than a century. Here we consider pattern formation in a gas
      phase, where beautiful but highly complex reaction-diffusion-convection dynamics
      are uncovered by means of a specific laser technique. A quantitative analysis
      reveals that two different, apparently independent processes, both highly
      correlated and synchronized across the extension of the reaction cloud, act on
      different time scales. Each of them imprints a different structure of salt
      precipitation at the tube walls. 

PMID- 27025406
TI  - Conflicting reports on the role of the glycemic effect of Catha edulis (Khat): A
      systematic review and meta-analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the leaves of Catha edulis
      Forsskal (Khat) are consumed by the people of Yemen primarily for its
      recreational effect, and secondarily, for achieving certain tasks. Additionally,
      Yemeni diabetics chew such leaves in the belief that this can control their
      elevated blood glucose level. AIMS: This review focuses on outlining the findings
      of studies that have been conducted to display the glycemic effect of Catha
      edulis, while trying to balance it with findings of the association of its
      chewing with the development of type 2 diabetes mellitus (DM). MATERIALS AND
      METHODS: The search strategy adopted was based on a comprehensive research in
      Medline, PubMed, Web of Science, JSTOR, Scopus and Cochrane for articles,
      proceeding abstracts and theses to identify complete reports written in the
      English language about the glycemic effect of Catha edulis in humans and animals
      from 1976 to 2016. In addition, bibliographies were also reviewed to find
      additional reports not otherwise published. Thirty seven records were identified
      of which, 25 eligible studies were included in the meta-analysis using blood
      glucose as an outcome measurement. Studies were divided into four subgroups
      according to the experimental model, namely; non-diabetic animals, diabetic
      animals, non-diabetic humans and diabetic humans. The pooled mean difference (MD)
      of blood glucose between experimental and control were calculated using random
      effects model of the weighted mean difference of blood glucose with 95%
      confidence interval (CI). Heterogeneity between studies was tested using I(2)
      statistic and a value of P<0.05 was considered to indicate statistical
      significance. RESULTS: The scientific reports in the literature prevailed that
      the glycemic effect of Catha edulis were greatly conflicting with the majority of
      studies indicating that Catha edulis has a mild hypoglycemic effect. However, the
      meta-analysis indicted that the overall result showed an insignificant reduction
      in blood glucose (MD=-9.70, 95% CI: -22.17 to 2.76, P=0.13, with high
      heterogeneity between subgroups, I(2)=88.2%, P<0.0001). In addition, pooled mean
      difference of blood glucose of non-diabetic animals, diabetic animals and non
      diabetic humans showed an insignificant reduction in blood glucose (MD=-18.55,
      95% CI: -39.55 to 2.50, P<0.08, MD=-52.13%, 95% CI: -108.24 to 3.99, P=0.07 and
      MD=-2.71%, 95% CI: -19.19 to -13.77, P=0.75) respectively. Conversely, a
      significant elevation in the pooled mean difference of blood glucose in diabetic
      humans was indicated (MD=67.18, 95% CI: 36.93-97.43, P<0.0001). The conflict
      shown in the glycemic effect of Catha edulis is thought to be cultivar-related,
      while demographic and epidemiological reports suggested that chewing Catha edulis
      might be a predisposing factor contributing to the development of type 2 DM.
      CONCLUSION: It was difficult to draw a meaningful conclusion from both the
      systematic and the meta-analysis with respect to the glycemic effect of Catha
      edulis since the meta-analysis results were insignificant with high heterogeneity
      among subgroups and are greatly conflicting. The variation is most likely due to
      unadjusted experimental factors or is related to Catha edulis itself, such as the
      differences in the phytochemical composition. Therefore, it is highly recommended
      that further studies of the glycemic effect of the cultivar of Catha edulis being
      studied should come with the identification and quantification of phytochemical
      content so that a meaningful assessment can be made with regard to its
      hypoglycemic properties. In addition, well-controlled clinical studies should be
      conducted to confirm whether or not chewing Catha edulis is associated with the
      development of type 2 DM, since this would be a source of concern seeing that the
      plant is widely consumed in certain populations.

PMID- 27025407
TI  - Overexpressing FSTL1 for Heart Repair.

PMID- 27025408
TI  - Nur77 gene expression levels were involved in different ACTH-secretion autonomy
      between Cushing's disease and subclinical Cushing's disease.
AB  - Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both
      diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary
      adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no
      Cushingoid features in subCD. The differences of molecular mechanisms in ACTH
      autonomy between CD and subCD have not yet been reported. Therefore, we aimed to
      investigate the differences in molecular mechanisms of ACTH-secretion autonomy
      between CD and subCD. The study included 23 patients [7 CD, 6 subCD, and 10 non
      functioning pituitary tumors (NFTs)] who underwent transsphenoidal surgery at the
      Osaka University Hospital between December 2009 and October 2013. Using
      quantitative real-time PCR, various ACTH-related gene expressions in tumor
      tissues from CD, subCD, and NFT were measured such as pro-opiomelanocortin
      (POMC), POMC transcription factor (Tpit, Pitx1, NeuroD1, and Nur77), POMC peptide
      processing enzymes (prohormone convertase: PC1/3 and PC2), and ACTH secretion
      related factors (corticotropin-releasing hormone receptor 1: CRHR1 and
      glucocorticoid receptor alpha: GRalpha). Only Nur77 mRNA levels were
      significantly higher in CD than in subCD. Furthermore, we stained 6 CD and 6
      subCD with anti-Nur77 antibody. All tumor samples from CD had Nur77 protein
      positive cells. On the other hand, Nur77 protein was expressed in only one tumor
      sample from subCD. This sample showed high expression of Nur77 mRNA. Nur77 is an
      important to regulate POMC transcription and negative-feedback by
      glucocorticoids. Nur77 gene expression levels might involve different autonomy of
      ACTH production between CD and subCD. 

PMID- 27025409
TI  - Ramucirumab: Boon or bane.
AB  - Ramucirumab is the recent addition to the list of monoclonal antibodies being
      tried in various malignancies. It has been approved in non-small cell lung
      cancer, gastric cancer and colorectal cancer after progression of one or more
      lines of therapies in the advanced setting. Though randomized trials have shown
      benefit, cost effectiveness is questionable. Moreover, the benefits shown are
      marginal, putting a question mark over its clinical usage. This review summarizes
      the latest evidence on ramucirumab. 

PMID- 27025410
TI  - Retrieving transient conformational molecular structure information from inner
      shell photoionization of laser-aligned molecules.
AB  - We discuss a scheme to retrieve transient conformational molecular structure
      information using photoelectron angular distributions (PADs) that have averaged
      over partial alignments of isolated molecules. The photoelectron is pulled out
      from a localized inner-shell molecular orbital by an X-ray photon. We show that a
      transient change in the atomic positions from their equilibrium will lead to a
      sensitive change in the alignment-averaged PADs, which can be measured and used
      to retrieve the former. Exploiting the experimental convenience of changing the
      photon polarization direction, we show that it is advantageous to use PADs
      obtained from multiple photon polarization directions. A simple single-scattering
      model is proposed and benchmarked to describe the photoionization process and to
      do the retrieval using a multiple-parameter fitting method. 

PMID- 27025412
TI  - Contributorships Are Not 'Weighable' to be Equal.
AB  - A new trend to assign some authors as 'first co-authors' is noticeable in
      scientific publications as a statement highlighting that two or more authors
      'contributed equally' to a reported work. However, the requirements of scientific
      rigor, honesty, and accuracy in academic standards make such statements invalid
      and, thus, should be avoided. A potential solution is to specify the role of each
      co-author, from study conception to communication of results, and let readers
      judge the importance of each contribution by themselves. Alternatively, authors
      should demonstrate how they contributed 'equally' when they are defined as 'equal
      contributors'.

PMID- 27025411
TI  - Mortality from asbestos-associated disease in Libby, Montana 1979-2011.
AB  - Research on asbestos exposure in Libby, MT, has focused on occupational exposure
      in vermiculite mining and processing, but less attention has been paid to
      asbestos-related mortality among community members without vermiculite mining
      occupational history. Our study reports on asbestos-related mortality in Libby
      over 33 years (1979-2011) while controlling for occupational exposure. We
      calculated sex-specific 33-year standardized mortality ratios (SMRs) for Libby
      residents who died from 1979 to 2011 with an asbestos-related cause of death.
      Decedent address at time of death was geocoded to confirm inclusion in the Libby
      County Division. We controlled for past W.R. Grace employment by including and
      then removing them from the SMR analysis. Six hundred and ninety-four decedents
      were identified as having at least one asbestos-related cause of death and
      residing in our study area boundary. Statistically significant (P<0.05) 33-year
      SMRs, both before and after controlling for W.R. Grace employment, were found
      for: male and female non-malignant respiratory diseases, female COPD, and
      asbestosis for both sexes combined. Eighty-five men and two women were matched to
      employment records. We observed elevated asbestos-related mortality rates among
      males and females. SMR results for asbestosis were high for both sexes, even
      after controlling for past W.R. Grace employment. These results suggest that the
      general population may be experiencing asbestos-related effects, not just former
      vermiculite workers. Additional research is needed to determine whether SMRs
      remain elevated after controlling for secondary exposure, such as living with
      vermiculite workers.

PMID- 27025413
TI  - Picrasidine N Is a Subtype-Selective PPARbeta/delta Agonist.
AB  - Recently, growing evidence of the pivotal roles of peroxisome proliferator
      activated receptor (PPAR) beta/delta in various physiological functions,
      including lipid homeostasis, cancer, and inflammation, has raised interest in
      this receptor. In this study, the naturally occurring dimeric alkaloid
      picrasidine N (1) from Picrasma quassioides was identified as a novel
      PPARbeta/delta agonist from a library consisting of plant extracts and natural
      compounds using a mammalian one-hybrid assay, and this compound was
      characterized. Compound 1 activated PPARbeta/delta but did not activate or
      slightly activated PPARalpha and PPARgamma. Furthermore, a peroxisome
      proliferator response element-driven luciferase reporter gene assay demonstrated
      that 1 enhanced PPARbeta/delta transcriptional activity. Moreover, 1 selectively
      induced mRNA expression of ANGPTL4, which is a PPAR target gene. This observation
      is quite different from previously identified synthetic PPARbeta/delta agonists,
      which can induce the expression of not only ANGPTL4 but also other PPAR target
      genes, such as ADRP, PDK4, and CPT-1. These results demonstrate that 1 is a
      potent subtype-selective and gene-selective PPARbeta/delta agonist, suggesting
      its potential as a lead compound for further drug development. This compound
      would also be a useful chemical tool for elucidating the mechanism of
      PPARbeta/delta-regulated specific gene expression and the biological significance
      of PPARbeta/delta. 

PMID- 27025414
TI  - Commentary on CT-guided percutaneous core-needle biopsy of pancreatic masses:
      comparison of the standard mesenteric/retroperitoneal versus the trans-organ
      approaches.

PMID- 27025416
TI  - Health and happiness.

PMID- 27025415
TI  - Glaucoma history and risk factors.
AB  - Apart from the risk of developing glaucoma there is also the risk that it is not
      detected and irreversible loss of vision ensues. Some studies of methods of
      glaucoma diagnosis have examined the results of instrument-based examinations
      with great if not complete reliance on objective findings in arriving at a
      diagnosis. The very valuable advances in glaucoma detection instrument
      technologies, and apparent increasing dependence on them, may have led to reduced
      consideration of information available from a patient history in those studies.
      Dependence on objective evidence of glaucomatous pathology may reduce the
      possibility of detecting glaucoma suspects or patients at risk for becoming
      glaucoma suspects. A valid positive family history of glaucoma is very valuable
      information. However, negative family histories can often be unreliable due to
      large numbers of glaucoma cases being undiagnosed. No evidence of family history
      is appropriate rather than no family history. In addition the unreliability of a
      negative family history is increased when patients with glaucoma fail to inform
      their family members. A finding of no family history can only be stated as no
      known family history. In examining the potential diagnostic contribution from a
      patient history, this review considers, age, frailty, race, type and degree of
      refractive error, systemic hyper- and hypotension, vasospasm, migraine,
      pigmentary dispersion syndrome, pseudoexfoliation syndrome, obstructive sleep
      apnea syndrome, diabetes, medication interactions and side effects, the degree of
      exposure to intraocular and intracranial pressure elevations and fluctuations,
      smoking, and symptoms in addition to genetics and family history of the disease.

PMID- 27025417
TI  - Cardiology technology--from old to new.

PMID- 27025418
TI  - Creating a healthier environment for the Chinese population.

PMID- 27025419
TI  - Left-to-right atrial shunting: new hope for heart failure?

PMID- 27025420
TI  - Learning from role modelling: making the implicit explicit.

PMID- 27025424
TI  - Somalia calls for greater coordination in health assistance.

PMID- 27025425
TI  - Eric Topol: innovator in cardiology and digital medicine.

PMID- 27025426
TI  - Child health, the refugees crisis, and economic recession in Greece.

PMID- 27025427
TI  - Barriers in palliative care in China.

PMID- 27025428
TI  - Medical education and medical professionalism in China.

PMID- 27025429
TI  - Inappropriate use of antibiotics in children in China.

PMID- 27025430
TI  - Integrating social health insurance systems in China.

PMID- 27025431
TI  - Challenges arising from China's two-child policy.

PMID- 27025432
TI  - Bioresorbable coronary scaffolds should disappear faster.

PMID- 27025433
TI  - Expectations of medical students in China.

PMID- 27025434
TI  - Department of Error.

PMID- 27025435
TI  - Unidirectional left-to-right interatrial shunting for treatment of patients with
      heart failure with reduced ejection fraction: a safety and proof-of-principle
      cohort study.
AB  - BACKGROUND: In patients with heart failure, interventions to reduce elevated left
      atrial pressure improve symptoms and reduce the risk of hospital admission. We
      aimed to assess the safety and potential efficacy of therapeutic left-to-right
      interatrial shunting in patients with heart failure with reduced ejection
      fraction. METHODS: We did this proof-of-principle cohort study at one centre in
      Canada. Patients (aged >=18 years) with New York Heart Association (NYHA) class
      III chronic heart failure with reduced ejection fraction were enrolled under the
      Canadian special access programme. Shunt implants were done after transseptal
      catheterisation with transoesophageal echocardiographic guidance under general
      anaesthesia. Patients had clinical and echocardiography evaluations at baseline
      and months 1 and 3 after shunt implantation. FINDINGS: Between Oct 10, 2013, and
      March 27, 2015, we enrolled ten patients. The device was successfully implanted
      in all patients; no device-related or procedural adverse events occurred during
      follow-up. Transoesophageal echocardiography at 1 month showed that all shunts
      were patent, with no thrombosis or migration. From baseline to 3 month follow-up,
      we recorded improvements in NYHA classification (from class III to class II in
      seven [78%] of nine patients, from class III to class I in one [11%] patient, and
      no change in one [11%] patient; p=0.0004); quality of life, as assessed by the
      Duke Activity Status Index (from a mean score of 13 [SD 6.2] to 24.8 [12.9];
      p=0.016) and the Kansas City Cardiomyopathy Questionnaire (from a mean score of
      44.3 [SD 9.8] to 79.1 [13.0]; p=0.0001); and 6 min walk test distance (from a
      mean of 244 m [SD 112] to 318 m [134]; p=0.016). Pulmonary capillary wedge
      pressure was reduced from a mean of 23 mm Hg (SD 5) at baseline to 17 mm Hg (8)
      at 3 months (p=0.035), with no changes in right atrial pressure, pulmonary
      arterial pressure, or pulmonary resistance. No patient was admitted to hospital
      for worsening heart failure. One (10%) patient was admitted to hospital with
      gastrointestinal bleeding at month 1; one (10%) patient died after incessant
      ventricular tachycardia storm, which led to terminal heart failure 2 months post
      procedure. INTERPRETATION: This first-in-man experience with an implanted left-to
      right interatrial shunt demonstrates initial safety and early beneficial clinical
      and haemodynamic outcomes in patients with heart failure with reduced ejection
      fraction. Further large-scale randomised studies are warranted. FUNDING: V-Wave.

PMID- 27025437
TI  - Management strategies and future challenges for aortic valve disease.
AB  - The management of aortic valve disease has been improved by accurate diagnosis
      and assessment of severity by echocardiography and advanced imaging techniques,
      efforts to elicit symptoms or objective markers of disease severity and
      progression, and consideration of optimum timing of aortic valve replacement,
      even in elderly patients. Prevalence of calcific aortic stenosis is growing in
      ageing populations. Conventional surgery remains the most appropriate option for
      most patients who require aortic valve replacement, but the transcatheter
      approach is established for high-risk patients or poor candidates for surgery.
      The rapid growth of transcatheter aortic valve replacement has been fuelled by
      improved technology, evidence-based clinical research, and setting up of
      multidisciplinary heart teams. Aortic regurgitation can be difficult to diagnose
      and quantify. Left ventricular dysfunction often precedes symptoms, needing
      active surveillance by echocardiography to determine the optimum time for aortic
      valve replacement. Development of transcatheter approaches for aortic
      regurgitation is challenging, owing to the absence of valvular calcification and
      distortion of aortic root anatomy in many patients. 

PMID- 27025436
TI  - A transcatheter intracardiac shunt device for heart failure with preserved
      ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1
      trial.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is a common,
      globally recognised, form of heart failure for which no treatment has yet been
      shown to improve symptoms or prognosis. The pathophysiology of HFPEF is complex
      but characterised by increased left atrial pressure, especially during exertion,
      which might be a key therapeutic target. The rationale for the present study was
      that a mechanical approach to reducing left atrial pressure might be effective in
      HFPEF. METHODS: The REDUCe Elevated Left Atrial Pressure in Patients with Heart
      Failure (REDUCE LAP-HF) study was an open-label, single-arm, phase 1 study
      designed to assess the performance and safety of a transcatheter interatrial
      shunt device (IASD, Corvia Medical, Tewkesbury, MA, USA) in patients older than
      40 years of age with symptoms of HFPEF despite pharmacological therapy, left
      ventricular ejection fraction higher than 40%, and a raised pulmonary capillary
      wedge pressure at rest (>15 mm Hg) or during exercise (>25 mm Hg). The study was
      done at 21 centres (all departments of cardiology in the UK, Netherlands,
      Belgium, France, Germany, Austria, Denmark, Australia, and New Zealand). The co
      primary endpoints were the safety and performance of the IASD at 6 months,
      together with measures of clinical efficacy, including functional capacity and
      clinical status, analysed per protocol. This study is registered with
      ClinicalTrials.gov, number NCT01913613. FINDINGS: Between Feb 8, 2014, and June
      10, 2015, 68 eligible patients were entered into the study. IASD placement was
      successful in 64 patients and seemed to be safe and well tolerated; no patient
      had a peri-procedural or major adverse cardiac or cerebrovascular event or need
      for cardiac surgical intervention for device-related complications during 6
      months of follow-up. At 6 months, 31 (52%) of 60 patients had a reduction in
      pulmonary capillary wedge pressure at rest, 34 (58%) of 59 had a lower pulmonary
      capillary wedge pressure during exertion, and 23 (39%) of 59 fulfilled both these
      criteria. Mean exercise pulmonary capillary wedge pressure was lower at 6 months
      than at baseline, both at 20 watts workload (mean 32 mm Hg [SD 8] at baseline vs
      29 mm Hg [9] at 6 months, p=0.0124) and at peak exercise (34 mm Hg [8] vs 32 [8],
      p=0.0255), despite increased mean exercise duration (baseline vs 6 months: 7.3
      min [SD 3.1] vs 8.2 min [3.4], p=0.03). Sustained device patency at 6 months was
      confirmed by left-to-right shunting (pulmonary/systemic flow ratio: 1.06 [SD
      0.32] at baseline vs 1.27 [0.20] at 6 months, p=0.0004). INTERPRETATION:
      Implantation of an interatrial shunt device is feasible, seems to be safe,
      reduces left atrial pressure during exercise, and could be a new strategy for the
      management of HFPEF. The effectiveness of IASD compared with existing treatment
      for patients with HFPEF requires validation in a randomised controlled trial.
      FUNDING: Corvia Medical Inc.

PMID- 27025438
TI  - Mitral valve disease--current management and future challenges.
AB  - The field of mitral valve disease diagnosis and management is rapidly changing.
      New understanding of disease pathology and progression, with improvements in and
      increased use of sophisticated imaging modalities, have led to early diagnosis
      and complex treatment. In primary mitral regurgitation, surgical repair is the
      standard of care. Treatment of asymptomatic patients with severe mitral
      regurgitation in valve reference centres, in which successful repair is more than
      95% and surgical mortality is less than 1%, should be the expectation for the
      next 5 years. Transcatheter mitral valve repair with a MitraClip device is also
      producing good outcomes in patients with primary mitral regurgitation who are at
      high surgical risk. Findings from clinical trials of MitraClip versus surgery in
      patients of intermediate surgical risk are expected to be initiated in the next
      few years. In patients with secondary mitral regurgitation, mainly a disease of
      the left ventricle, the vision for the next 5 years is not nearly as clear.
      Outcomes from ongoing clinical trials will greatly inform this field. Use of
      transcatheter techniques, both repair and replacement, is expected to
      substantially expand. Mitral annular calcification is an increasing problem in
      elderly people, causing both mitral stenosis and regurgitation which are
      difficult to treat. There is anecdotal experience with use of transcatheter
      valves by either a catheter-based approach or as a hybrid technique with open
      surgery, which is being studied in early feasibility trials. 

PMID- 27025439
TI  - Valvular aspects of rheumatic heart disease.
AB  - Acute rheumatic fever and rheumatic heart disease remain major global health
      problems. Although strategies for primary and secondary prevention are well
      established, their worldwide implementation is suboptimum. In patients with
      advanced valvular heart disease, mechanical approaches (both percutaneous and
      surgical) are well described and can, for selected patients, greatly improve
      outcomes; however, access to centres with experienced staff is very restricted in
      regions that have the highest prevalence of disease. Development of diagnostic
      strategies that can be locally and regionally provided and improve access to
      expert centres for more advanced disease are urgent and, as yet, unmet clinical
      needs. We outline current management strategies for valvular rheumatic heart
      disease on the basis of either strong evidence or expert consensus, and highlight
      areas needing future research and development. 

PMID- 27025440
TI  - GenoMatrix: A Software Package for Pedigree-Based and Genomic Prediction Analyses
      on Complex Traits.
AB  - Genomic and pedigree-based best linear unbiased prediction methodologies (G-BLUP
      and P-BLUP) have proven themselves efficient for partitioning the phenotypic
      variance of complex traits into its components, estimating the individuals'
      genetic merits, and predicting unobserved (or yet-to-be observed) phenotypes in
      many species and fields of study. The GenoMatrix software, presented here, is a
      user-friendly package to facilitate the process of using genome-wide marker data
      and parentage information for G-BLUP and P-BLUP analyses on complex traits. It
      provides users with a collection of applications which help them on a set of
      tasks from performing quality control on data to constructing and manipulating
      the genomic and pedigree-based relationship matrices and obtaining their
      inverses. Such matrices will be then used in downstream analyses by other
      statistical packages. The package also enables users to obtain predicted values
      for unobserved individuals based on the genetic values of observed related
      individuals. GenoMatrix is available to the research community as a Windows 64bit
      executable and can be downloaded free of charge at:
      http://compbio.ufl.edu/software/genomatrix/.

PMID- 27025441
TI  - Prevalence of depression in patients with type 2 diabetes attended in primary
      care in Spain.
AB  - OBJECTIVES: To estimate the prevalence of known and undiagnosed depression in
      patients with type 2 diabetes attended in primary care setting in Spain, and to
      determine the factors associated with the presence of depression. METHODS: This
      was a cross-sectional and multicenter study performed in a random sample of
      patients with type 2 diabetes attended in 21 primary care centers. Depressive
      symptoms were measured with the self-administered Patient Health Questionnaire
      (PHQ-9). RESULTS: A total of 411 patients were analyzed (mean age 70.8 (SD 10.3)
      years; 53.8% women). 29.2% of patients met the diagnostic criteria of depression,
      of whom 17% had known depression and 12.2% undiagnosed depression (PHQ-9 score
      >=10, without a previous diagnosis of depression). Depression was more common in
      women (43.4%; 95% confidence interval [CI] 34.5-52.3%), widow (33.3%; 95% CI 27.9
      38.7%), and hypothyroidism (12.5%; 95% CI 8.7-16.3%). Cardiovascular risk
      factors, the degree of control, complications related to diabetes, antidiabetic
      therapy and the number of drugs were not associated with the presence of
      depression. CONCLUSIONS: The prevalence of depression was high in patients with
      type 2 diabetes. However, in approximately 40% of patients depression was
      undiagnosed. The complications related to diabetes and antidiabetic therapy were
      not associated with the presence of depression.

PMID- 27025442
TI  - The effect of cooling management on blood flow to the dominant follicle and
      estrous cycle length at heat stress.
AB  - The use of ultrasound imaging for the examination of reproductive organs has
      contributed substantially to the fertility management of dairy cows around the
      world. This method has many advantages such as noninvasiveness and immediate
      availability of information. Adding Doppler index to the ultrasound imaging
      examination, improved the estimation of blood volume and flow rate to the ovaries
      in general and to the dominant follicle in particular. The aim of this study was
      to examine changes in the blood flow to the dominant follicle and compare them to
      the follicular development throughout the cycle. We further set out to examine
      the effects of different types of cooling management during the summer on the
      changes in blood flow to the dominant follicle. For this purpose, 24 Israeli
      Holstein dairy cows, under heat stress, were randomly assigned one of two groups:
      one was exposed to five cooling sessions per day (5CS) and the other to eight
      cooling sessions per day (8CS). Blood flow to the dominant follicle was measured
      daily using Doppler index throughout the estrous cycle. No differences in the
      preovulatory dominant follicle diameter were detected between the two cooling
      management regimens during the cycle. However, the length of the first follicular
      wave was significantly longer, whereas the second follicular wave was
      nonsignificantly shorter in the 5CS group as compared to the 8CS group. In
      addition, no difference in blood flow was found during the first 18 days of the
      cycle between the two groups. However, from Day 20 until ovulation a higher rate
      of blood flow was measured in the ovaries of cows cooled 8 times per day as
      compared to the 5CS group. No differences in progesterone levels were noted.
      Finally, the estrous cycle length was shorter in the 8CS group as compared to the
      5CS group. Our data suggest that blood flow to the dominant follicle and estrous
      cycle length is affected by heat stress. Using the appropriate cooling management
      during heat stress can enhance the blood flow to the ovary and may contribute to
      improved fertility in dairy cows. 

PMID- 27025443
TI  - Accessing the exceptional points of parity-time symmetric acoustics.
AB  - Parity-time (PT) symmetric systems experience phase transition between PT exact
      and broken phases at exceptional point. These PT phase transitions contribute
      significantly to the design of single mode lasers, coherent perfect absorbers,
      isolators, and diodes. However, such exceptional points are extremely difficult
      to access in practice because of the dispersive behaviour of most loss and gain
      materials required in PT symmetric systems. Here we introduce a method to
      systematically tame these exceptional points and control PT phases. Our
      experimental demonstration hinges on an active acoustic element that realizes a
      complex-valued potential and simultaneously controls the multiple interference in
      the structure. The manipulation of exceptional points offers new routes to
      broaden applications for PT symmetric physics in acoustics, optics, microwaves
      and electronics, which are essential for sensing, communication and imaging. 

PMID- 27025444
TI  - Early adversity contributes to chronic stress induced depression-like behavior in
      adolescent male rhesus monkeys.
AB  - Chronic stress is an important cause for depression. However, not everyone who is
      exposed to chronic stress will develop depression. Our previous studies
      demonstrated that early adversity can cause lasting changes in adolescent rhesus
      monkeys, but depressive symptoms have not been observed. Compared to adults, it
      is still unknown that whether adolescent rhesus monkeys experiencing early
      adversity are more likely to develop depressive symptoms. In this study, we
      investigated the long term relationship between early adversity, chronic stress
      and adolescent depression for the first time. Eight male rhesus monkeys were
      reared in maternal separation (MS) or mother-reared (MR) conditions. All of them
      went through unpredictable chronic stress for two months at their age four. The
      stressors included space restriction, intimidation, long illumination and
      fasting. Behavioral and physiological data were collected during the experiment.
      The results showed that, compared with the MR group, the locomotor activity of MS
      group was significantly decreased after one month of chronic stress while
      huddling up and stereotypical behaviors were significantly increased. Moreover,
      this trend continued and even worsened at the second month. Significantly higher
      hair cortisol levels and lower body weight were observed in MS group after two
      months of stress. These results indicate that early adversity is one of the
      environmental factors which can increase the susceptibility of depression when
      experiencing chronic stress in the later life. This will further clarify the
      important roles of early environmental factors in the development of adolescent
      depression and children rearing conditions should receive more attention.

PMID- 27025446
TI  - Histone deacetylase inhibition prevents the impairing effects of hippocampal
      gastrin-releasing peptide receptor antagonism on memory consolidation and
      extinction.
AB  - Hippocampal gastrin-releasing peptide receptors (GRPR) regulate memory formation
      and extinction, and disturbances in GRPR signaling may contribute to cognitive
      impairment associated with neurodevelopmental disorders. Histone acetylation is
      an important epigenetic mechanism that regulates gene expression involved in
      memory formation, and histone deacetylase inhibitors (HDACis) rescue memory
      deficits in several models. The present study determined whether inhibiting
      histone deacetylation would prevent memory impairments produced by GRPR blockade
      in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of
      saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory
      avoidance (IA) training, followed by an infusion of either SAL or the selective
      GRPR antagonist RC-3095 immediately after training. In a second experiment, the
      infusions were administered before and after a retention test trial that served
      as extinction training. As expected, RC-3095 significantly impaired consolidation
      and extinction of IA memory. More importantly, pretraining administration of NaB,
      at a dose that had no effect when given alone, prevented the effects of RC-3095.
      In addition, the combination of NaB and RC-3095 increased hippocampal levels of
      the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC
      inhibition can protect against memory impairment caused by GRPR blockade.

PMID- 27025445
TI  - Vocal training, levodopa, and environment effects on ultrasonic vocalizations in
      a rat neurotoxin model of Parkinson disease.
AB  - Levodopa does not improve dysarthria in patients with Parkinson Disease (PD),
      although vocal exercise therapy, such as "LSVT/LOUD((r))", does improve vocal
      communication. Most patients receive vocal exercise therapy while concurrently
      being treated with levodopa, although the interaction between levodopa and vocal
      exercise therapy on communication in PD is relatively unknown. Further, carryover
      of vocal exercise therapy to novel situations is critical for successful
      outcomes, but the influence of novel situations on rehabilitated vocal
      communication is not well understood. To address the influence of exercise,
      medications, and environment on vocal communication with precise experimental
      control, we employed the widely used 6-OHDA rat neurotoxin model of PD (infusion
      to the medial forebrain bundle), and assessed ultrasonic vocalizations after:
      vocal exercise, vocal exercise with levodopa, levodopa alone, and control
      conditions. We tested USVs in the familiar training environment of the home cage
      and a novel cage. We hypothesized that parkinsonian rats that undergo vocal
      exercise would demonstrate significant improvement of ultrasonic vocalization
      (USV) acoustic parameters as compared to the control exercise and levodopa-only
      treatment groups. We further hypothesized that vocal exercise in combination with
      levodopa administration, similar to what is common in humans, would lead to
      improvement in USV outcomes, particularly when tested in a familiar versus a
      novel environment. We found that the combination of exercise and levodopa lead to
      some improvement in USV acoustic parameters and these effects were stronger in a
      familiar vs. a novel environment. Our results suggest that although treatment can
      improve aspects of communication, environment can influence the benefits of these
      effects.

PMID- 27025447
TI  - Femoral Shaft Torsion in Injured and Uninjured Ballet Dancers and Its Association
      with Other Hip Measures: A Cross-sectional Study.
AB  - Low range femoral torsion, termed "lateral shaft torsion," has been associated
      with greater range of hip external rotation and turnout in dancers. It is also
      hypothesized that achieving greater turnout at the hip minimizes torsion at the
      knee, shank, ankle, and foot, and consequently reduces incidence of lower limb
      injuries. The primary aims of this study were to investigate: 1. differences in
      range of femoral shaft torsion between dancers with and without lower limb
      injuries; and 2. the relationship between femoral shaft torsion, hip external
      rotation range, and turnout. A secondary aim was to examine the relationship
      between femoral shaft torsion and other hip measures: hip strength, lower limb
      joint hypermobility, hip stability, and foot progression angle, as explanatory
      variables. Demographic, dance, and injury data were collected, along with
      physical measures of femoral shaft torsion, hip rotation range of motion, and
      turnout. Hip strength, control, lower limb hypermobility, and foot progression
      angle were also measured. Eighty female dancers, 50 with lower limb injury (20.7
      +/- 4.8 years of age) and 30 without lower limb injury (17.8 +/- 4.1 years of
      age), participated in the study. There was no difference in range of femoral
      shaft torsion between the groups (p = 0.941). Femoral shaft torsion was weakly
      correlated with range of hip external rotation (r = -0.034, p = 0.384) and
      turnout (r = -0.066, p = 0.558). Injured dancers had a significantly longer
      training history than non-injured dancers (p = 0.001). It was concluded that
      femoral shaft torsion does not appear to be associated with the overall incidence
      of lower limb injury in dancers or to be a primary factor influencing extent of
      turnout in this population.

PMID- 27025448
TI  - Differences in Preseason Aerobic Fitness Screening in Professional and Pre
      professional Modern Dancers.
AB  - The aerobic demands of today's dance repertoire warrant understanding of the
      current cardiorespiratory fitness of dancers. The purpose of this study was to
      compare aerobic fitness levels of professional and pre-professional modern
      dancers and determine change over time. A retrospective analysis of four groups,
      two professional, and two pre-professional, was conducted in preseason annual
      screens, occurring before the professional dancers' rehearsal period and the
      students' academic training. Resting (HRrest), peak (HRpeak), and recovery
      (HRrecov) heart rate, and blood pressure (BP) were compared in 577 dancers, using
      an accelerated 3-minute step test. Smoking, asthma, and aerobic and cross
      training rates between groups were also compared. A 4 (group) X 2 (gender) MANOVA
      design determined differences between groups and genders in all dependent
      variables (p < 0.05). Using a repeated measures ANOVA design, we compared a
      subgroup over 3 years and one pre-professional group over 4 years. There were
      differences between groups in systolic BP and all HR variables (p < 0.001).
      Professional dancers reflected better cardiorespiratory fitness than pre
      professional dancers. There were differences between groups in aerobic and cross
      training activities but no differences in smoking incidence or asthma rates. Pre
      professional dancers demonstrated improvement in aerobic fitness over time (p =
      0.006) while professionals did not change. Professional dancers display better
      aerobic fitness, which may reflect their performance demands. Wellness programs
      appear to enhance fitness in pre-professional dance students over time.
      Additional aerobic training is recommended for pre-professional modern dance
      students to prepare them for the performance demands of a professional career.

PMID- 27025449
TI  - Attentional Focus in Classical Ballet: A Survey Of Professional Dancers.
AB  - Focus of attention and its effects on skilled motor performance has become an
      important line of research in the motor learning domain. Numerous studies have
      demonstrated that an external focus of attention (i.e., on the movement effect)
      enhances motor performance and learning relative to an internal focus (i.e., on
      body movements). Thus, small differences in the wording of instructions or
      feedback given by teachers can have a significant impact on the effectiveness and
      efficiency of motor skill performance. In this paper, we review some of the
      attentional focus studies that are relevant to ballet performance. In addition,
      we report the findings of a survey among professional ballet dancers (N = 53)
      that we conducted to determine their typical attentional focus while performing
      certain movements. The results showed that the majority adopted internal foci, or
      combinations of internal and external foci, most of the time. This suggests that
      there is room for improvement for performance and teaching. We provide examples
      of how external foci can be promoted in ballet practice.

PMID- 27025450
TI  - Injuries in a Professional Ballet Dance Company: A 10-year Retrospective Study.
AB  - Ballet dancers are high-performance athletes who are particularly susceptible to
      a wide variety of musculoskeletal injuries. However, they are relatively
      understudied, and data on their injury rates are lacking. This retrospective
      study features the largest aggregate data on professional ballet dancers to date
      and aims to identify the most common diagnoses and areas of injury in this unique
      population to better direct preventative and clinical practices. The study
      encompassed a 10-year period from January 2000 to December 2010 of dancers from a
      single company. Data regarding the dancers' age, gender, location of injury, and
      diagnosis were collected from workers' compensation claims, company records, and
      medical records maintained by the treating doctors. These were analyzed to
      determine metrics on injury incidence, frequency, and diagnosis. Over the 10-year
      span, 574 injuries occurred. There were approximately 52 dancers per year for a
      total of 153 who danced at least one complete season during the study period. The
      average age was 27, and 53% were female. Given turnover with retirement and
      replacements, the total number of dancer-years was 520, indicating an injury
      incidence per annum of 1.10 (574 injuries per 520 dancer-years). The most common
      locations of injury were foot and ankle and the lumbar spine, with the three most
      common diagnoses making up greater than a third (37%) of the total. As the
      current largest study in professional ballet, the findings set the benchmark
      metrics for musculoskeletal injury to the foot, ankle, and lumbar spine sites.
      Future studies should aim to identify injury risk factors and modalities for
      prevention of these injuries.

PMID- 27025451
TI  - The Influence of Two Stretching Techniques on Standing Hip Range of Motion.
AB  - The purpose of this study was to describe the effects of two stretching
      techniques on standing hip range of motion (ROM) in female dancers. The
      participants were 18 university students. They were randomly assigned to one of
      three groups: active stretch group (Bartenieff Fundamentals(TM) thigh lift),
      passive stretch group (contract-release-contract form of PNF), or a control
      group. The participants assigned to the stretching groups completed 12 sessions
      of their randomly assigned stretch technique over a 3-week period. A repeated
      measures ANOVA (group x day) was used to analyze statistically the data gathered
      on the pre- and post-standing hip ROM tests. Both of the stretching groups had
      statistically significant increases in standing hip flexion angles during the
      standing hip flexion test. The passive stretch group had greater increases than
      the active stretch group [F(4, 86) = 7.03, p < 0.01]. The results of this study
      provide evidence that the effects of supine stretching transfer to standing hip
      flexion.

PMID- 27025452
TI  - Analysis of Factors That Influence Long-Term Independent Living for Elderly
      Subarachnoid Hemorrhage Patients.
AB  - BACKGROUND: The number of elderly subarachnoid hemorrhage (SAH) patients has been
      increasing. The aim of this study was to analyze long-term outcome for elderly
      (>=75 years) SAH patients and to establish a treatment strategy. METHODS: From
      January 2005 to December 2013, 86 consecutive cases were treated. We used a
      modified Rankin Scale (mRS) at the outpatient clinic or a telephone interview of
      patients and/or families. Kaplan-Meier plots were done for mortality and
      independent (mRS 0 ~ 2) state. Multivariate analysis was done to distinguish
      factors that influence on outcome. RESULTS: Median age was 79, Hunt-Kosnik grade
      1 ~ 3 was 79%, and the radical intervention (clipping or coiling) rate was 78%.
      Mean follow-up period was 28.7 +/- 3.4 standard error months. Half of deaths
      occurred during the first two months. The number of cases of independent living
      gradually decreased to 50% at 28 months after SAH. Half of patients lived
      independently for 36 months at HK grades 1 to 3, and 3 months at HK grades 4 to 5
      (p < 0.05). Half of patients lived independently for 40 months in the radical
      intervention group, and 14 months in the conservative treatment group (p < 0.05).
      Multivariate analysis for independent living revealed that gender, pre-morbid
      condition, HK grade, and postoperative complication were significant (p < 0.05).
      CONCLUSIONS: Good-grade elderly SAH cases that were independent pre-stroke should
      have radical intervention performed for aneurysm. Avoiding perioperative
      complications have a positive influence on long-term independent living.

PMID- 27025453
TI  - Tuberous Sclerosis Health Care Utilization Based on the National Inpatient Sample
      Database: A Review of 5655 Hospitalizations.
AB  - INTRODUCTION: Tuberous sclerosis complex (TSC) has an incidence of 1/6000 in the
      general population. Overall care may be complex and costly. We examine trends in
      health care utilization and outcomes of patients with TSC over the last decade.
      METHODS: The National Inpatient Sample (NIS) database for inpatient
      hospitalizations was searched for admission of patients with TSC. RESULTS: During
      2000-2010, the NIS recorded 5655 patients with TSC. Most patients were admitted
      to teaching hospitals (71.7%). Over time, the percentage of craniotomies
      performed per year remained stable (P = 0.351). Relevant diagnoses included neuro
      oncologic disease (5.4%), hydrocephalus (6.5%), and epilepsy (41.2%).
      Hydrocephalus significantly increased length of stay and hospital charges. A
      higher percentage of patients who underwent craniotomy had hydrocephalus (29.8%
      vs. 5.3%; P < 0.001), neuro-oncologic disease (43.5% vs. 3.4%; P < 0.001), other
      cranial diseases (4.2% vs. 1.2%; P < 0.001), and epilepsy (61.4% vs. 40.1%; P <
      0.001). CONCLUSIONS: Our study identifies aspects of inpatient health care
      utilization, outcomes, and cost of a large number of patients with TSC. These
      aspects include related diagnoses and procedures that contribute to longer length
      of stay, increased hospital cost, and increased in-hospital mortality, which can
      inform strategies to reduce costs and improve care of patients with TSC.

PMID- 27025454
TI  - Intraoperative Transcranial Motor-Evoked Potentials Predict Motor Function
      Outcome in Intracerebral Hemorrhage Surgery.
AB  - OBJECTIVE: Prediction of motor function after intracerebral hemorrhage (ICH)
      often poses a diagnostic challenge. This study was performed to investigate
      whether intraoperative monitoring of motor-evoked potentials (MEPs) could predict
      postoperative motor function recovery. METHODS: We reviewed 16 consecutive
      patients undergoing evacuation of supratentorial ICH with hemiplegia between June
      2011 and October 2014. Patients were categorized according to the results of MEPs
      before and after evacuation of hematoma. The correlation between detection of
      MEPs and prognosis of motor function was analyzed. RESULTS: In 10 of 16 cases
      (62%), stable MEPs were detected before and after evacuation of hematoma, and
      postoperative motor function was improved in all cases, including 3 cases with
      severe preoperative motor impairment on manual muscle test (1-2). In 3 cases
      (19%) in which MEPs were not detected throughout the procedure, motor function
      was not improved. In the other 3 cases (19%), MEPs were not measured before
      evacuation of ICH but were detected after evacuation despite poor prognosis of
      motor function. The results of postevacuation MEPs were considered false-negative
      results. Predictions using pre-evacuation MEP results were completely consistent
      with prognosis for recovery, whereas MEPs obtained during and after evaluation
      were useful for monitoring. CONCLUSIONS: Intraoperative MEPs may indicate
      preservation of pyramidal tracts, and pre-evacuation MEPs can predict motor
      function outcome after ICH surgery.

PMID- 27025455
TI  - Human platelet activation by Escherichia coli: roles for FcgammaRIIA and integrin
      alphaIIbbeta3.
AB  - Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic
      syndrome in which thrombotic disorders can be found. Direct platelet-bacterium
      interactions might contribute to some of these conditions; however, mechanisms of
      human platelet activation by E. coli leading to thrombus formation are poorly
      understood. While the IgG receptor FcgammaRIIA has a key role in platelet
      response to various Gram-positive species, its role in activation to Gram
      negative bacteria is poorly defined. This study aimed to investigate the
      molecular mechanisms of human platelet activation by E. coli, including the
      potential role of FcgammaRIIA. Using light-transmission aggregometry,
      measurements of ATP release and tyrosine-phosphorylation, we investigated the
      ability of two E. coli clinical isolates to activate platelets in plasma, in the
      presence or absence of specific receptors and signaling inhibitors. Aggregation
      assays with washed platelets supplemented with IgGs were performed to evaluate
      the requirement of this plasma component in activation. We found a critical role
      for the immune receptor FcgammaRIIA, alphaIIbbeta3, and Src and Syk tyrosine
      kinases in platelet activation in response to E. coli. IgG and alphaIIbbeta3
      engagement was required for FcgammaRIIA activation. Moreover, feedback mediators
      adenosine 5'-diphosphate (ADP) and thromboxane A2 (TxA2) were essential for
      platelet aggregation. These findings suggest that human platelet responses to E.
      coli isolates are similar to those induced by Gram-positive organisms. Our
      observations support the existence of a central FcgammaRIIA-mediated pathway by
      which human platelets respond to both Gram-negative and Gram-positive bacteria. 

PMID- 27025456
TI  - Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell
      lymphoma.
AB  - The t(11;14) translocation resulting in constitutive cyclin D1 expression is an
      early event in mantle cell lymphoma (MCL) transformation. Patients with a highly
      proliferative phenotype produce cyclin D1 transcripts with truncated 3'UTRs that
      evade miRNA regulation. Here, we report the recurrence of a novel gene fusion in
      MCL cell lines and MCL patient isolates that consists of the full protein coding
      region of cyclin D1 (CCND1) and a 3'UTR consisting of sequences from both the
      CCND1 3'UTR and myotonic dystrophy kinase-related Cdc42-binding kinase's (MRCK)
      intron one. The resulting CCND1/MRCK mRNA is resistant to CCND1-targeted miRNA
      regulation, and targeting the MRCK region of the chimeric 3'UTR with siRNA
      results in decreased CCND1 levels. 

PMID- 27025458
TI  - Prediction and detection models for acute kidney injury in hospitalized older
      adults.
AB  - BACKGROUND: Acute Kidney Injury (AKI) occurs in at least 5 % of hospitalized
      patients and can result in 40-70 % morbidity and mortality. Even following
      recovery, many subjects may experience progressive deterioration of renal
      function. The heterogeneous etiology and pathophysiology of AKI complicates its
      diagnosis and medical management and can add to poor patient outcomes and incur
      substantial hospital costs. AKI is predictable and may be avoidable if early risk
      factors are identified and utilized in the clinical setting. Timely detection of
      undiagnosed AKI in hospitalized patients can also lead to better disease
      management. METHODS: Data from 25,521 hospital stays in one calendar year of
      patients 60 years and older was collected from a large health care system. Four
      machine learning models (logistic regression, support vector machines, decision
      trees and naive Bayes) along with their ensemble were tested for AKI prediction
      and detection tasks. Patient demographics, laboratory tests, medications and
      comorbid conditions were used as the predictor variables. The models were
      compared using the area under ROC curve (AUC) evaluation metric. RESULTS:
      Logistic regression performed the best for AKI detection (AUC 0.743) and was a
      close second to the ensemble for AKI prediction (AUC ensemble: 0.664, AUC
      logistic regression: 0.660). History of prior AKI, use of combination drugs such
      as ACE inhibitors, NSAIDS and diuretics, and presence of comorbid conditions such
      as respiratory failure were found significant for both AKI detection and risk
      prediction. CONCLUSIONS: The machine learning models performed fairly well on
      both predicting AKI and detecting undiagnosed AKI. To the best of our knowledge,
      this is the first study examining the difference between prediction and detection
      of AKI. The distinction has clinical relevance, and can help providers either
      identify at risk subjects and implement preventative strategies or manage their
      treatment depending on whether AKI is predicted or detected.

PMID- 27025457
TI  - Contribution of Human Fibroblasts and Endothelial Cells to the Hallmarks of
      Inflammation as Determined by Proteome Profiling.
AB  - In order to systematically analyze proteins fulfilling effector functionalities
      during inflammation, here we present a comprehensive proteome study of
      inflammatory activated primary human endothelial cells and fibroblasts. Cells
      were stimulated with interleukin 1-beta and fractionated in order to obtain
      secreted, cytoplasmic and nuclear protein fractions. Proteins were submitted to a
      data-dependent bottom up analytical platform using a QExactive orbitrap and the
      MaxQuant software for protein identification and label-free quantification.
      Results were further combined with similarly generated data previously obtained
      from the analysis of inflammatory activated peripheral blood mononuclear cells.
      Applying a false discovery rate of less than 0.01 at both, peptide and protein
      level, a total of 8370 protein groups assembled from 117,599 peptides was
      identified; mass spectrometry data have been made fully accessible via
      ProteomeXchange with identifier PXD003406 to PXD003417.Comparative proteome
      analysis allowed us to determine common and cell type-specific inflammation
      signatures comprising novel candidate marker molecules and related expression
      patterns of transcription factors. Cardinal features of inflammation such as
      interleukin 1-beta processing and the interferon response differed substantially
      between the investigated cells. Furthermore, cells also exerted similar
      inflammation-related tasks; however, by making use of different sets of proteins.
      Hallmarks of inflammation thus emerged, including angiogenesis, extracellular
      matrix reorganization, adaptive and innate immune responses, oxidative stress
      response, cell proliferation and differentiation, cell adhesion and migration in
      addition to monosaccharide metabolic processes, representing both, common and
      cell type-specific responsibilities of cells during inflammation.

PMID- 27025460
TI  - Electrochemical Redox Switchable Dispersion of Single-Walled Carbon Nanotubes in
      Water.
AB  - We present a new, efficient approach to achieve superior dispersibility of single
      walled carbon nanotubes (SWNTs) in water by integrating reversible host-guest
      interaction and pi-pi stacking. In this approach, beta-cyclodextrin (beta-CD) was
      first modified with a pyrene group to be adsorbed onto the wall of pristine SWNTs
      via pi-pi stacking, followed by further functionalization with ferrocene (Fc)
      terminated water-soluble poly(ethylene glycol) (PEG) through supramolecular host
      guest interaction between beta-CD and Fc. Upon alternate electrochemical
      oxidative/reductive stimuli, the reversible host-guest pair enabled the PEG-Fc@Py
      CD@SWNTs to exhibit switchable conversion between dispersion and aggregation
      states. Electric field controllable PEG-Fc@Py-CD@SWNTs with good reversibility
      and intact nanotube structure may find potential applications in selective
      screening of SWNTs, biosensors, and targeted drug delivery.

PMID- 27025459
TI  - Revealing the kinetics of Leishmania chagasi infection in the male genital system
      of hamsters.
AB  - BACKGROUND: Leishmaniasis causes alterations and lesions in the genital system,
      which leads to azoospermia and testicular atrophy in animals during the chronic
      phase of the infection. The aim of this study was to reveal the kinetics of
      Leishmania chagasi infection in the genital system of male golden hamsters
      (Mesocricetus auratus). METHODS: Animals were intraperitoneally inoculated with
      amastigotes from L. chagasi. At different time points animals were euthanized and
      genital organs processed for histo-pathological, qPCR, cytokines and testosterone
      detection assays. RESULTS: Our results showed a high parasite load in testis,
      followed by an increase of pro-inflammatory cytokines IL1-beta, TNF-alpha and IFN
      gamma, and testosterone. Subsequently, IL-4 expression was upregulated and basal
      parasite persistence in testis was observed using the experimental approach.
      CONCLUSION: Extracellular amastigotes migrated to the epididymis posing as a
      potential major factor of parasite persistence and venereal transmission of L.
      chagasi infection in hamsters.

PMID- 27025462
TI  - Climate change and mental health: Rationale for research and intervention
      planning.

PMID- 27025461
TI  - Layered transition metal dichalcogenides: promising near-lattice-matched
      substrates for GaN growth.
AB  - Most III-nitride semiconductors are grown on non-lattice-matched substrates like
      sapphire or silicon due to the extreme difficulty of obtaining a native GaN
      substrate. We show that several layered transition-metal dichalcogenides are
      closely lattice-matched to GaN and report the growth of GaN on a range of such
      layered materials. We report detailed studies of the growth of GaN on
      mechanically-exfoliated flakes WS2 and MoS2 by metalorganic vapour phase epitaxy.
      Structural and optical characterization show that strain-free, single-crystal
      islands of GaN are obtained on the underlying chalcogenide flakes. We obtain
      strong near-band-edge emission from these layers, and analyse their temperature
      dependent photoluminescence properties. We also report a proof-of-concept
      demonstration of large-area growth of GaN on CVD MoS2. Our results show that the
      transition-metal dichalcogenides can serve as novel near-lattice-matched
      substrates for nitride growth. 

PMID- 27025464
TI  - Current adherence attitudes can reflect the course and outcome of bipolar
      disorder-type I.

PMID- 27025463
TI  - Demographic, clinical and psychological characteristics of patients with self
      harm behaviours attending an emergency department of a tertiary care hospital.
AB  - Understanding the characteristics of those with self-harm behaviour may help in
      identifying those at risk and providing targeted interventions to this group of
      patients, especially in the emergency services. The present study aimed to
      compare the suicidal intent, hopelessness, severity of depressive symptoms, and
      personality traits of those with and without psychiatric disorders, presenting
      with a self-harming behaviour to the emergency setting. For this, patients
      presenting to the emergency department of a tertiary care hospital with self-harm
      behaviour were evaluated for presence or absence of a psychiatric diagnosis,
      suicidal intent, personality traits, depressive symptoms and hopelessness by
      using structured instruments. The present study included 132 participants. The
      mean age of the sample was 28.7 years and the male: female ratio of 1.28:1. At
      least one psychiatric diagnosis was present in 41.7% of the sample, depression
      and substance use disorders being most common among them. Impulsive suicide
      attempt was present in 40.2% of the sample. Those with a psychiatric diagnosis
      were more likely to be older, males, married, have higher suicidal intent, more
      planned attempts and higher depressive symptoms as compared to those who did not
      have a psychiatric disorder. Impulsive suicide attempters had lower suicidal
      intent than non-impulsive attempters. Present study suggests that those
      presenting to the emergency with self-harm behaviour comprises 2 interrelated
      groups, differing on certain demographic features, severity of depressive
      symptoms, suicidal intent and impulsivity. 

PMID- 27025465
TI  - Course of illness in comorbid bipolar disorder and obsessive-compulsive disorder
      patients.
AB  - Psychiatric comorbidity is extremely common. One of the most common and difficult
      to manage comorbid conditions is the co-occurrence of bipolar disorder (BD) and
      obsessive compulsive disorder (OCD). We updated our recent systematic review
      searching the electronic databases MEDLINE, Embase, and PsycINFO to investigate
      course of illness in BD-OCD patients. We identified a total of 13 relevant papers
      which found that the majority of comorbid OCD cases appeared to be related to
      mood episodes. OC symptoms in comorbid patients appeared more often during
      depressive episodes, and comorbid BD and OCD cycled together, with OC symptoms
      often remitting during manic/hypomanic episodes. 

PMID- 27025466
TI  - Psychiatric classification: Current debate and future directions.
AB  - Classification of health related conditions can be a complex task. This is
      particularly so in case of psychiatric disorders. The present paper reviews the
      fundamentals of psychiatric classification, including its basis, history, methods
      of evaluation, the journey so far and future directions. The various criticisms
      of current classificatory systems and possible solutions are discussed. Special
      reference to the research domain criteria (RDoC) approach has been made and
      implications discussed. 

PMID- 27025467
TI  - Validation of the Malayalam version of the Internalized Stigma of Mental Illness
      (ISMI) scale.
AB  - Little is known about internalized stigma of mental illness in India. A reason
      for this could be the lack of valid assessment instruments adapted for the
      diverse cultures and languages of the country. One of the most widely used and
      accepted questionnaires to assess internalized stigma is the 29-item Internalized
      Stigma of Mental Illness (ISMI) scale. The aim of the present study was to
      translate and adapt the ISMI to the Malayalam-speaking population of Kerala,
      India and to assess its content and factorial validity. The content validity of
      the Malayalam-language ISMI was studied through interviews with 7 experts on
      stigma in India. Factorial validity was examined by means of a confirmatory
      factor analysis (CFA) based on a cross-sectional survey among 290 patients with
      mental illness attending follow-up outpatient and primary care clinics in Kerala,
      India. The expert panel concluded that the items of the translated questionnaire
      adequately represent internalized stigma in the Malayalam-speaking population of
      Kerala. The theorized factor structure of the ISMI consisting of five factors
      showed a suboptimal model fit (WRMR=0.940; TLI=0.971, CFI=0.948; RMSEA=0.059)
      which improved considerably after removal of the stigma resistance factor and
      three items with poor factor loadings (WRMR=0.819; TLI=0.982, CFI=0.966;
      RMSEA=0.051). Although our study identifies some sources of model ill-fit, it
      shows that a reduced version of the Malayalam-language ISMI can be a valuable
      tool for the study of internalized stigma in this cultural setting. 

PMID- 27025468
TI  - Forensic issues of involuntary admissions: The Achilles heel of psychiatry
      residency in general hospital psychiatry unit in India.

PMID- 27025469
TI  - Safety and effectiveness of divalproex sodium extended release containing regimen
      in Indian patients with bipolar I disorder in continuation phase: Results of
      EASED registry.
AB  - The study was conducted to evaluate the safety and effectiveness of divalproex
      sodium XR containing regimen in patients with bipolar disorder (BPD) who are in
      continuation phase. It was an open-label, prospective, observational study
      conducted from July 2010 to December 2011 at 48 sites across India. Adult
      patients with bipolar I disorder of manic or mixed type fulfilling the DSM-IV
      criteria and who were in the continuation phase were included. Safety (primary
      outcome) was assessed by incidence of treatment emergent adverse events (AEs).
      Effectiveness (secondary outcome), was evaluated by proportion of patients who
      did not have a relapse, change in Clinical Global Impression Score-BP version
      Severity of Illness (CGI-BP) and Young's Mania Rating Scale (YMRS) score. Data
      was recorded at three visits: visit-1 (baseline), visit-2 (end of 2 months +/- 7
      days) and visit-3 (end of 4 months +/- 14 days), and summarised using descriptive
      statistics. p<0.05 was considered statistically significant. A total of 489 and
      468 patients were included in the safety and effectiveness analyses,
      respectively. Of the 66 AEs reported, 57 (89.0%) were mild and 7 (10.9%) were
      moderate (data missing for 2 events). In total, 75.0% (48/64) of the AEs were
      related to the study drug. No serious AEs reported (N=64). No relapse observed in
      93.3% of patients. There was a significant (p<0.0001) reduction in the YMRS and
      CGI-BP scores from baseline to visit-3. Our study confirms the results of earlier
      studies in terms of good tolerability and effectiveness of divalproex sodium XR
      containing regimen in this study population.

PMID- 27025470
TI  - Knowledge of dementia among Vietnamese American immigrants.

PMID- 27025471
TI  - Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An
      updated meta-analysis.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of
      folate/homocysteine metabolic pathway. C677T polymorphism of MTHFR gene was
      reported as risk factor for congenital defects, metabolic and neuropsychiatric
      disorders. Numerous case-control studies investigated C677T polymorphism as risk
      factor for schizophrenia but results of these studies were contradictory. To draw
      a conclusion, a meta-analysis of all available case-control studies was
      performed. PubMed, Google Scholar, Springer Link and Elsevier databases were
      searched for eligible case-control studies. Pooled odds ratio with 95%CI was used
      as an association measure and all statistical analyses were performed by Open
      Meta-Analyst and MIX software. Total 38 studies with 10,069 cases and 13,372
      controls were included in the present meta-analysis. Results of meta-analysis
      showed significant associated between C677T polymorphism and risk of
      schizophrenia (ORTvsC=1.18, 95%CI=1.10-1.27, p=<0.001; ORCTvsCC=1.10, 95%CI=1.04
      1.17, p=<0.001; ORTTvsCC=1.40, 95%CI=1.20-1.64, p=<0.001; ORTT+CTvsCC=1.19,
      95%CI=1.09-1.30, p=<0.001). We also performed subgroup and sensitivity analyses.
      Subgroup analysis was done according to ethnicity and significant association was
      found between C677T polymorphism and risk of schizophrenia in all three ethnic
      populations-African (OR=2.51; 95%CI=1.86-3.40; p=<0.001), Asian (OR=1.21;
      95%CI=1.10-1.33; p=<0.001) and Caucasian (OR=1.07; 95%CI=1.01-1.14; p=0.01). In
      conclusion the results of the present meta-analysis suggested that the MTHFR
      C677T polymorphism is a risk factor for schizophrenia. 

PMID- 27025472
TI  - Post-Traumatic Stress Disorder in pre-schoolers: A report of two cases.
AB  - Post-Traumatic Stress Disorder (PTSD) presents unique challenges in toddlers and
      pre-schoolers as there are difficulties in assessment and overshadowing by
      comorbid illnesses. We present case descriptions of two pre-schoolers with
      developmental manifestations of the PTSD symptoms of intrusion, avoidance and
      alteration in arousal and reactivity following penetrative sexual abuse. These
      symptoms caused significant impairment and required a combination of
      pharmacological and psychotherapeutic intervention. This case report facilitates
      recognition of the disorder in preverbal and early verbal children and
      suggestions on management of PTSD in pre-schoolers are provided. 

PMID- 27025473
TI  - Prevalence of anxiety and depression symptoms and their relationship with other
      coronary artery disease risk factors: A population-based study on 5900 residents
      in Southeast Iran.
AB  - INTRODUCTION: Anxiety and depression are reported as the most prevalent
      psychiatric disorders worldwide. Here, we studied the prevalence of such
      disorders with co-morbidities of coronary artery disease (CAD) risk factors in an
      urban population in Iran. METHODS: 5900 people were selected from 15 to 75-years
      olds through single-stage cluster sampling. In addition to examining them for CAD
      risk factors, Beck anxiety and depression inventories were used to measure
      anxiety and depression symptoms. The standardized population prevalence of such
      disorders is reported and the predictors of having anxiety or depression were
      assessed using Poisson regression model. RESULTS: Overall 25.4% had moderate and
      22.7% had severe anxiety. Severe anxiety significantly and constantly increased
      by age groups (p=0.01). The risk for anxiety was higher among females (Adjusted
      Risk Ratio, ARR 1.2), and those who were student/soldier (ARR 1.07). Those with
      high level of physical activity were at lower risk for anxiety (ARR 0.92). The
      risk of depression (any level) was higher among females (ARR 1.3), those holding
      high-school level of education (ARR 1.41), and those who used opium either
      occasionally (ARR 1.17) or frequently (ARR 1.3). Both anxiety and depression were
      significantly associated with two main CAD risk factors, low physical activity
      and opium use. CONCLUSION: We found that the majority of residents in Kerman,
      particularly women, are suffering from mild to server depression and anxiety
      symptoms. Public health interventions to increase public awareness on such
      symptoms, screening and delivery of prevention and treatment services are
      required to prevent from the growing burden of such disorders and cardiovascular
      diseases.

PMID- 27025474
TI  - Progress in psychiatric nosology: A hard-nosed look.

PMID- 27025475
TI  - The first complete Mag family retrotransposons discovered in Drosophila.
AB  - A retrotransposon of the Mag family was found in the Drosophila simulans genome
      for the first time. We also identified novel transposable elements representing
      the Mag family in seven Drosophila species. The high similarity between the 3'
      and 5' long terminal repeats in the found copies of transposable elements
      indicates that their retrotransposition has occurred relatively recently. Thus,
      the Mag family of retrotransposons is quite common for the genus Drosophila. 

PMID- 27025476
TI  - Mod(mdg4)-58.8, isoform of mod(mdg4) loci, directly interacts with MTACP1A and
      MTACP1B proteins of Drosophila melanogaster.
AB  - As a result of experiments in yeast two-hybrid system, coimmunoprecipitation of
      proteins from D. melanogaster embryo cell lysate, and immunostaining, it was
      shown for the first time that Mod(mdg4)-58.8 protein (isoform P), a product of
      mod(mdg4) locus, directly interacts with mtACP1A and mtACP1B proteins. These
      proteins are involved in de novo biosynthesis of fatty acids in mitochondria and
      are required for normal gametogenesis in males and females and, possibly, for the
      trachea development. This result expands the understanding of the role of
      mod(mdg4) locus products in the regulation of life activity of the eukaryotic
      cell. 

PMID- 27025477
TI  - Recombinant 1F9 spidroin microgels for murine full-thickness wound repairing.
AB  - The study of the stimulating effect of the microgels (MGs) based on recombinant
      1F9 spidroin on the regeneration of the deep skin wound in mice was carried out.
      The use of spidroin MGs was shown to increase significantly the quality of
      healing compared to the control. The introduction of the MG in the wound edges
      led to recovery of all the structural elements of the skin: the epidermis, the
      dermis, including vascular and nervous network, in the periphery of the wound
      underlying muscles, and skin appendages (sebaceous and sweat glands and hair
      follicles) was revealed. 

PMID- 27025478
TI  - Mathematics analysis of polymerase chain reaction kinetic curves.
AB  - The paper reviews different approaches to the mathematical analysis of polymerase
      chain reaction (PCR) kinetic curves. The basic principles of PCR mathematical
      analysis are presented. Approximation of PCR kinetic curves and PCR efficiency
      curves by various functions is described. Several PCR models based on chemical
      kinetics equations are suggested. Decision criteria for an optimal function to
      describe PCR efficiency are proposed. 

PMID- 27025479
TI  - Physicochemical conversion of human exometabolites for the NaCl involvement into
      the mass exchange in closed life support systems.
AB  - The results of the original physicochemical method of NaCl recovery out of the
      mineralized human metabolites' solution obtained after their oxidation in H2O2
      aqueous solution under the influence of alternating electric current are
      presented. The technological stages of the newly developed method are described,
      and its efficiency at each stage is demonstrated. The possibility to efficiency
      isolate Na from the NaHCO3 solution by applying electrodialysis technology and
      temperature separation is demonstrated. The HCl synthesis from Cl2 and H2
      released during electrolysis is stable, allowing its combining with
      electrodialysis aimed at NaCl production under the conditions of a closed life
      support system. 

PMID- 27025480
TI  - Characteristics of fatty acid composition of Gammarus lacustris inhabiting lakes
      with and without fish.
AB  - The effect of a biotic factor--the presence of predatory fish in water--on the
      composition and content of fatty acids in crustaceans was studied in the
      populations of the lake amphipod Gammarus lacustris from two lakes with fish and
      three lakes without fish. It was found that, at an overall increase in the
      quantity and quality of food resources (namely, increase in the content of
      eicosapentaenoic acid and docosahexaenoic acid (DHA) in the biomass), the
      relative rate of DHA accumulation in gammarids in the lakes without fish is
      higher than in the lake with fish.

PMID- 27025481
TI  - Genomic and proteomic profiles of Acholeplasma laidlawii strains differing in
      sensitivity to ciprofloxacin.
AB  - As a result of comparative analysis of complete genomes as well as cell and
      vesicular proteomes of A. laidlawii strains differing in sensitivity to
      ciprofloxacin, it was first shown that the mycoplasma resistance to the
      antibiotic is associated with the reorganization of genomic and proteomic
      profiles, which concerns many genes and proteins involved in fundamental cellular
      processes and realization of bacterial virulence. 

PMID- 27025482
TI  - The strengthening role of D:D interactions in fibrin self-assembly under
      oxidation.
AB  - The effect on ozone-induced oxidation on the self-assembly of fibrin in the
      presence of fibrin-stabilizing factor FXIIIa of soluble cross-linked fibrin
      oligomers was studied in a medium containing moderate urea concentrations. It is
      established that fibrin oligomers were formed by the protofibrils cross-linked
      through gamma-gamma dimers and the fibrils additionally cross-linked by through
      alpha-polymers. The oxidation promoted both the accumulation of greater amounts
      of gamma-gamma dimers and the formation of protofibrils, fibrils, and their
      dissociation products emerging with increasing urea concentrations, which have a
      high molecular weight. It is concluded that the oxidation enhances the axial
      interactions between D-regions of fibrin molecules. 

PMID- 27025483
TI  - Audiogenic epilepsy and GABAergic system of the colliculus inferior in Krushinsky
      Molodkina rats.
AB  - GABAergic brain system is an important link in the pathological circuits of
      rodent audiogenic epilepsy (AE). The number of GABAergic neurons in the inferior
      colliculi of KM strain rats (AE prone) was not different from that of the control
      non-prone strain. At the same time, the glutamate decarboxylase mRNA expression
      (the key enzyme of GABA synthesis) was 5 times higher than in control. The data
      evidence that the GABAergic system does play an important role in AE proneness. 

PMID- 27025484
TI  - Highly immunogenic variant of attenuated vaccinia virus.
AB  - The LIVPDelta6 strain of vaccinia virus (VACV) was created by genetic engineering
      on the basis of previously obtained attenuated 1421ABJCN strain by target
      deletion of the A35R gene encoding an inhibitor of antigen presentation by the
      major histocompatibility complex class II. 1421ABJCN is the LIVP strain of VACV
      with five inactivated virulence genes encoding hemagglutinin (A56R), gamma
      interferon-binding protein (B8R), thymidine kinase (J2R), complement-binding
      protein (C3L), and Bcl2-like inhibitor of apoptosis (N1L). The highly immunogenic
      LIVPDelta6 strain could be an efficient fourth-generation attenuated vaccine
      against smallpox and other orthopoxvirus infections. 

PMID- 27025485
TI  - New interpretation of the redox properties of cytochrome b559 in photosystem II.
AB  - A model of heme-quinone redox interaction has been developed for cytochrome b559
      in photosystem II. The quinone QC in the singly protonated form may function as
      an interacting quinone. The electrostatic effect between the charges on the heme
      iron of the cytochrome and QCH leads to appearance of three forms of the
      cytochrome with different redox potentials. A simple and effective mechanism of
      redox regulation of the electron transfer pathways in photosystem II is proposed.

PMID- 27025486
TI  - Pressure algometry and enzyme-linked immunosorbent assay of natural antibodies in
      the evaluation of pain syndrome.
AB  - The dynamics of possible markers of pain syndrome: pain pressure thresholds of
      intolerance (PTI) and natural antibodies to mediators of pain processing (nAbs)
      in blood serum at dorsalgia was studied. We have shown that most men and women
      had reduced PTIs. Night PTIs were lower than daytime PTIs regardless of the
      gender. The study of the content of nAbs to opioids and biogenic amines by ELISA
      have shown a prolonged maintenance of their elevated and high levels that could
      evoke long-term effect in pain chronization. Thus, the pressure algometry and
      ELISA of nAbs to pain processing mediators make it possible to assess the
      individual pain status objectively and, on this bases, to propose personal
      schemes of treatment. 

PMID- 27025487
TI  - Metagenomic bacterial community profiles of chicken embryo gastrointestinal tract
      by using T-RFLP analysis.
AB  - Thirty microbial phylotypes of microorganisms were found in the gastrointestinal
      tract of chicken belonging to the Hajseks White breed, and 38 phylotypes were
      found in the gastrointestinal tract of chicken belonging to the Hajseks Brown
      breed. The microbiome of the gastrointestinal tract of the chicken embryos of the
      Hajseks White breed was dominated by the typical representatives of avian
      intestinal microflora--bacteria of the family Enterobacteriaceae (47.3%), orders
      Actinomycetales (13.6%) and Bifidobacteriales (20.6%), and the family
      Lachnospiraceae (1.1%). The microbiome of the gastrointestinal tract of the
      chicken embryos of the Hajseks Brown breed was dominated by the pathogenic
      bacteria of the order Rickettsiales (94.8%). The metagenome of gastrointestinal
      tract of both breeds also contained a small number of genes of unidentified
      bacteria.

PMID- 27025488
TI  - Nuclear mtDNA pseudogenes as a source of new variants of mitochondrial genes: A
      case study of Siberian rubythroat Luscinia calliope (muscicapidae, aves).
AB  - First evidence for the presence of copies of mitochondrial cytochrome b gene of
      the subspecies group Luscinia calliope anadyrensis-L. c. camtschatkensis in the
      nuclear genome of nominative L. c. calliope was obtained, which indirectly
      indicates the nuclear origin of the subspecies-specific mitochondrial haplotypes
      in Siberian rubythroat. This fact clarifies the appearance of mitochondrial
      haplotypes of eastern subspecies by exchange between the homologous regions of
      the nuclear and mitochondrial genomes followed by fixation by the founder effect.
      This is the first study to propose a mechanism of DNA fragment exchange between
      the nucleus and mitochondria (intergenomic recombination) and to show the role of
      nuclear copies of mtDNA as a source of new taxon-specific mitochondrial
      haplotypes, which implies their involvement in the microevolutionary processes
      and morphogenesis. 

PMID- 27025489
TI  - Drosophila polytene chromosome bands formed by gene introns.
AB  - Genetic organization of bands and interbands in polytene chromosomes has long
      remained a puzzle for geneticists. It has been recently demonstrated that
      interbands typically correspond to the 5'-ends of house-keeping genes, whereas
      adjacent loose bands tend to be composed of coding sequences of the genes. In the
      present work, we made one important step further and mapped two large introns of
      ubiquitously active genes on the polytene chromosome map. We show that
      alternative promoter regions of these genes map to interbands, whereas introns
      and coding sequences found between those promoters correspond to loose grey
      bands. Thus, a gene having its long intron "sandwiched" between to alternative
      promoters and a common coding sequence may occupy two interbands and one band in
      the context of polytene chromosomes. Loose, partially decompacted bands appear to
      host large introns. 

PMID- 27025490
TI  - The effect of gamma-radiation on resting eggs and life cycle of cladoceran Moina
      macrocopa.
AB  - We investigated the effects of gamma-irradiation on the survival of resting eggs
      of the cladoceran Moina macrocopa and on the parameters of the life cycle of
      neonates hatched from the irradiated eggs. It was shown that gamma-irradiation in
      a wide range of doses (from the background level to 100 Gy) had no effect on
      survival of eggs and mortality of neonates hatched from the irradiated eggs.
      However, exceeding the absorbed dose of 40 Gy sharply decreased the reproductive
      potential of the neonates hatched from irradiated eggs. 

PMID- 27025491
TI  - The antitumor effect of magnetic nanodisks and DNA aptamer conjugates.
AB  - Here we describe a method of forming large arrays (up to 10(9) pieces) of free
      magnetic Ni-nanodisks 50 nm thick coated on both sides with layers of 5 nm thick
      Au. The antitumor effect of the magnetic nickel gold-coated nanodisks and DNA
      aptamer conjugates was evaluated in vivo and in vitro. Under the influence of
      rotating magnetic field, the studied nanodisks can cause the death of Ehrlich
      ascites carcinoma cells. 

PMID- 27025492
TI  - Development of a biosensor for electrochemical detection of tumor-associated
      proteins in blood plasma of cancer patients by aptamers.
AB  - A molecular biosensor based on DNA aptamers (aptasensor) for the diagnosis of
      lung cancer in blood plasma samples was designed. To create the aptasensor, the
      aptamer 17_80, obtained in the study of postoperative material, was used. The
      affinity and binding selectivity of the aptamer 17_80 to the lung tumor tissue
      was confirmed on histological sections of postmortem samples of lung tissue.
      Using affinity enrichment and mass spectrometry, a possible target molecule of
      the aptamer 17_80, vimentin, was found. 

PMID- 27025493
TI  - Signal molecules during the organism development: Central and peripheral sources
      of noradrenaline in rat ontogenesis.
AB  - Using the method of high performance liquid chromatography with electrochemical
      detection, the age dynamics of the content of noradrenaline (NA) in the brain,
      adrenal gland, and the organ of Zuckerkandl in prenatal (18th and 21st days of
      embryogenesis) and early postnatal (3, 7, 15, and 30th days) periods of
      development was studied. The potential contribution of these organs to the
      formation of physiologically active concentration of noradrenalin in the blood
      was also assessed. The results suggest that, during the development of the
      organism, the activity of the sources of noradrenaline in the general circulation
      changes, which gives a reason to assume the existence of humoral interaction
      between NA-producing organs in the perinatal period of ontogenesis. 

PMID- 27025494
TI  - Molecular mechanism of modulation of nociceptive neuron membrane excitability by
      a tripeptide.
AB  - Using the whole-cell patch-clamp method, the ability of arginine-containing
      tripeptide Ac-RER-NH2, dipeptide Ac-RR-NH2, and free Arg molecule to modulate the
      membrane excitability of nociceptors was studied. Extracellular Ac-RER-NH2 upon
      interaction with the outer membrane of the nociceptive neuron decreases the Zeff
      value of the activation gating system of Nav1.8 channels. Thus, the tripeptide Ac
      RER-NH2 can be considered as a new effective and safe analgesic. 

PMID- 27025495
TI  - Weather sensitivity for zoo visitation in Toronto, Canada: a quantitative
      analysis of historical data.
AB  - Based on a case study of the Toronto Zoo (Canada), multivariate regression
      analysis, involving both climatic and social variables, was employed to assess
      the relationship between daily weather and visitation. Zoo visitation was most
      sensitive to weather variability during the shoulder season, followed by the off
      season and, then, the peak season. Temperature was the most influential weather
      variable in relation to zoo visitation, followed by precipitation and, then, wind
      speed. The intensity and direction of the social and climatic variables varied
      between seasons. Temperatures exceeding 26  degrees C during the shoulder season
      and 28  degrees C during the peak season suggested a behavioural threshold
      associated with zoo visitation, with conditions becoming too warm for certain
      segments of the zoo visitor market, causing visitor numbers to decline. Even
      light amounts of precipitation caused average visitor numbers to decline by
      nearly 50 %. Increasing wind speeds also demonstrated a negative influence on zoo
      visitation.

PMID- 27025497
TI  - Family history predictors of BRCA1/BRCA2 mutation status among Tunisian
      breast/ovarian cancer families.
AB  - BACKGROUND: With the increasing request for BRCA1/BRCA2 mutation tests, several
      risk models have been developed to predict the presence of mutation in these
      genes; in this study, we have developed an efficient BRCA genetic testing
      strategy. METHOD: As first step, to identify predictor variables associated with
      BRCA status, we have undertaken a cumulative mutation analysis including data
      from three Tunisian studies. Then, we have developed a logistic regression model
      for predicting the likelihood of harboring a BRCA mutation. Using receiver
      operating characteristic curves (ROC), an effective evaluation was performed. A
      total of 92 Tunisian families were included. Overall, 27 women were positive for
      BRCA1/BRCA2 deleterious mutations. RESULTS: Tow recurrent mutations (c.211dupA
      and c.5266dupC) explained 76 % of BRCA1-related families and three recurrent
      mutations (c.1310_1313del, c.1542_1547delAAGA and c.7887_7888insA) explained 90 %
      of BRCA2-related families. Early age at diagnosis of breast cancer, ovarian
      cancer, bilateral breast cancer were associated with BRCA1, whereas male breast
      cancer and four or more breast cancer cases in the family were associated with
      BRCA2. The area under the receiver operating characteristic curve of the risk
      score was 0.802 (95 % confidence interval = 0.0699-0. 905). CONCLUSION: Logistic
      regression reported particular profiles related to BRCA germline mutation
      carriers in our population, as well as an efficient prediction model that may be
      a useful tool for increasing the cost-effectiveness of genetic testing strategy.

PMID- 27025496
TI  - The impact and origin of copy number variations in the Oryza species.
AB  - BACKGROUND: Copy number variation (CNV), a complex genomic rearrangement, has
      been extensively studied in humans and other organisms. In plants, CNVs of
      several genes were found to be responsible for various important traits; however,
      the cause and consequence of CNVs remains largely unknown. Recently released next
      generation sequencing (NGS) data provide an opportunity for a genome-wide study
      of CNVs in rice. RESULTS: Here, by an NGS-based approach, we generated a CNV map
      comprising 9,196 deletions compared to the reference genome 'Nipponbare'. Using
      Oryza glaberrima as the outgroup, 80% of the CNV events turned out to be
      insertions in Nipponbare. There were 2,806 annotated genes affected by these CNV
      events. We experimentally validated 28 functional CNV genes including OsMADS56,
      BPH14, OsDCL2b and OsMADS30, implying that CNVs might have contributed to
      phenotypic variations in rice. Most CNV genes were found to be located in non-co
      linear positions by comparison to O. glaberrima. One of the origins of these non
      co-linear genes was genomic duplications caused by transposon activity or double
      strand break repair. Comprehensive analysis of mutation mechanisms suggested an
      abundance of CNVs formed by non-homologous end-joining and mobile element
      insertion. CONCLUSIONS: This study showed the impact and origin of copy number
      variations in rice on a genomic scale.

PMID- 27025498
TI  - Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with
      adjuvant radiotherapy for breast cancer.
AB  - Conservative management of breast cancer represents the standard treatment for
      early disease. Breast conserving surgery associated with radiotherapy for stage I
      II has been proven to be as equally effective as mastectomy in term of local
      control, distant disease, and overall survival. The growing minimal invasive
      surgical approach on the axillary region, and the new breast reconstructive
      techniques, will probably lead to a significant decrease of the rate of side
      effects related to mastectomy. Therefore, the adverse events caused by adjuvant
      radiation still remain a challenge. Cutaneous, pulmonary and cardiac toxicity
      represent the main toxicities of adjuvant radiotherapy for breast cancer. Safety
      profile of radiation is strongly dependent on the multidisciplinary management of
      the single case (systemic treatment, endocrine therapy, surgery), individual
      characteristics (i.e., co-morbidities, age, habits), and radiation-related
      aspects. Radiation techniques development, and facilities implementation
      concerning organs-at-risk sparing systems (i.e., image-guided radiotherapy,
      tracking systems, respiratory gating), represent brand new tools for the clinical
      oncologist, that would certainly minimize toxicity profile in the next future.
      However, data reported from published literature will greatly help physicians, to
      give to the patients appropriate counseling regarding the efficacy and potential
      adverse events of treatments, thus optimizing the informed decision-making
      process.

PMID- 27025499
TI  - Cerebral sinovenous thrombosis (CSVT) in children: what the pediatric
      radiologists need to know.
AB  - Cerebral sinovenous thrombosis (CSVT) is a relatively uncommon and potentially
      life-threatening condition in childhood, occurring in various clinical settings.
      Nowadays, however, it is increasingly diagnosed as related to many causes, likely
      due to greater clinical awareness and improvement of neuroradiologic techniques.
      The prompt diagnosis is an important goal to significantly reduce the risk of
      acute complications and long-term sequelae. The purpose of this narrative
      overview is to provide a useful educational tool in daily clinical practice for
      radiologists with a broad perspective of CSVT including a discussion of more
      common potential pitfalls related to misinterpretation of images in children.
      This paper will also review the normal venous anatomy, its variants, risk factors
      that contribute to cause CSVT (neonates with their specific causes of CSVT are
      not included in this review) and the practical imaging feature of cerebral
      sinovenous thrombosis on MRI and CT. Finally, a brief overview of frequent and
      severe CSVT conditions in children with key points in imaging is shown. 

PMID- 27025500
TI  - The appropriacy of averaging in the study of context effects.
AB  - Models of human decision-making aim to simultaneously explain the similarity,
      attraction, and compromise effects. However, evidence that people show all three
      effects within the same paradigm has come from studies in which choices were
      averaged over participants. This averaging is only justified if those
      participants show qualitatively similar choice behaviors. To investigate whether
      this was the case, we repeated two experiments previously run by Trueblood
      (Psychonomic Bulletin & Review, 19(5), 962-968, 2012) and Berkowitsch,
      Scheibehenne, and Rieskamp (Journal of Experimental Psychology, 143(3), 1331
      1348, 2014). We found that individuals displayed qualitative differences in their
      choice behavior. In general, people did not simultaneously display all three
      context effects. Instead, we found a tendency for some people to show either the
      similarity effect or the compromise effect but not both. More importantly, many
      individuals showed strong dimensional biases that were much larger than any
      effects of context. This research highlights the dangers of averaging
      indiscriminately and the necessity for accounting for individual differences and
      dimensional biases in decision-making.

PMID- 27025501
TI  - Pop-out and pop-in: Visual working memory advantages for unique items.
AB  - Attentional control is thought to play a critical role in determining the amount
      of information that can be stored and retrieved from visual working memory (VWM).
      We tested whether and how task-irrelevant feature-based salience, known to affect
      the control of visual attention, affects VWM performance. Our results show that
      features of a task-irrelevant color singleton are more likely to be recalled from
      VWM than non-singleton items and that this increased memorability comes at a cost
      to the other items in the display. Furthermore, the singleton effect in VWM was
      negatively correlated with an individual's baseline VWM capacity. Taken together,
      these results suggest that individual differences in VWM storage capacity may be
      partially attributable to the ability to ignore differences in task-irrelevant
      physical salience.

PMID- 27025502
TI  - Do Arabic numerals activate magnitude automatically? Evidence from the
      psychological refractory period paradigm.
AB  - A single experiment (N = 30) tested the claim that Arabic numerals automatically
      activate their magnitude representations by assessing whether central attention
      is required in order to activate magnitude within the psychological refractory
      period (PRP) paradigm. Subjects performed a color discrimination task as Task 1
      and a parity judgment task as Task 2. Task overlap was controlled by varying
      stimulus onset asynchrony (SOA). A spatial-numerical association of response
      codes (SNARC) effect arose in Task 2 and yielded under-additive effects with
      decreasing SOA. This result suggests that magnitude is activated prior to central
      attention, and is therefore consistent with the claim that numerals activate
      magnitude automatically.

PMID- 27025503
TI  - Erratum to: Mutation induction by inhaled radon progeny modeled at the tissue
      level.

PMID- 27025504
TI  - A rare cause of cerebral venous thrombosis: cryptococcal meningoencephalitis.
AB  - Cryptococcal meningoencephalitis (CM) is a serious central nervous system
      infection caused by Cryptococcus neoformans, seen mostly in immunocompromised
      hosts and less in immunocompetent patients. The vast majority of cryptococcosis
      cases are seen as human immunodeficiency virus infections with advanced
      immunosuppression. Meningitis and meningoencephalitis are the most common
      clinical manifestations. Nevertheless, immunocompetent patients with CM are
      rarely reported. Cerebral venous sinus thrombosis is a rare complication of CM.
      Here, we report an immunocompetent patient with CM from a non-endemic area, who
      presented with an acute onset and atypical symptoms associated with cerebral
      venous thrombosis. 

PMID- 27025505
TI  - The Independent Effects of Strength Training in Cancer Survivors: a Systematic
      Review.
AB  - Cancer treatment is associated with adverse changes in strength, body
      composition, physical function, and quality of life. Exercise training reduces
      cancer incidence and mortality rates and may offset some of the treatment-related
      effects. To determine the independent effects of strength training (ST) on the
      effects of cancer treatment, an initial search was performed in March and then
      updated in November 2015. Additional articles were identified by scanning
      references from relevant articles. Studies using traditional ST on strength, body
      composition, aerobic capacity, functional assessments, and psychosocial
      parameters were included. Excluded studies had no objective strength measurement
      or combined ST with additional exercise. Mean and standard deviations from 39
      studies across seven cancer types were extracted for main outcomes. ST-induced
      change scores with 95% confidence intervals were calculated and were evaluated
      with paired t tests, where appropriate. Twenty to fifty percent improvements in
      maximal strength were observed, indicating that the ST programs were effective.
      Physical function was also enhanced (7-38%), although gains were less consistent.
      Body composition and psychosocial changes were rare, with only a few changes in
      selected cancer types. As such, ST appears to promote benefits that may be
      specific to cancer types. Strength was the only consistent outcome that improved
      in all cancer survivors. However, these gains in strength are still of tremendous
      importance, given its impact on functionality and quality of life. Several
      practical considerations for exercise testing, training, and data reporting are
      presented for consideration to improve the overall depth of the field.

PMID- 27025506
TI  - Effects of a rapid-resisted elliptical training program on motor, cognitive and
      neurobehavioral functioning in adults with chronic traumatic brain injury.
AB  - This small clinical trial utilized a novel rehabilitation strategy, rapid
      resisted elliptical training, in an effort to increase motor, and thereby
      cognitive, processing speed in ambulatory individuals with traumatic brain injury
      (TBI). As an initial step, multimodal functional abilities were quantified and
      compared in 12 ambulatory adults with and 12 without TBI. After the baseline
      assessment, the group with TBI participated in an intensive 8-week daily exercise
      program using an elliptical trainer and was reassessed after completion and at an
      8-week follow-up. The focus of training was on achieving a fast movement speed,
      and once the target was reached, resistance to motion was increased in small
      increments to increase intensity of muscle activation. Primary outcomes were:
      High-Level Mobility Assessment Tool (HiMAT), instrumented balance tests, dual
      task (DT) performance and neurobehavioral questionnaires. The group with TBI had
      poorer movement excursion during balance tests and poorer dual-task (DT)
      performance. After training, balance reaction times improved and were correlated
      with gains in the HiMAT and DT. Sleep quality also improved and was correlated
      with improved depression and learning. This study illustrates how brain injury
      can affect multiple linked aspects of functioning and provides preliminary
      evidence that intensive rapid-resisted training has specific positive effects on
      dynamic balance and more generalized effects on sleep quality in TBI.

PMID- 27025507
TI  - Causes of death in 2877 patients with myelodysplastic syndromes.
AB  - Patients with myelodysplastic syndromes face a poor prognosis. The exact causes
      of death have not been described properly in the past. We performed a
      retrospective analysis of causes of death using data of 3792 patients in the
      Dusseldorf registry who have been followed up for a median time of 21 months.
      Medical files as well as death certificates were screened and primary care
      physicians were contacted. Death after AML evolution, infection, and bleeding was
      considered to be clearly disease-related. Further categories of causes of death
      were heart failure, other possibly disease-related reasons, such as
      hemochromatosis, disease-independent reasons as well as cases with unclear causes
      of death. Median age at the time of diagnosis was 71 years. At the time of
      analysis, 2877 patients (75.9 %) had deceased. In 1212 cases (42.1 %), the exact
      cause of death could not be ascertained. From 1665 patients with a clearly
      documented cause of death, 1388 patients (83.4 %) succumbed directly disease
      related (AML (46.6 %), infection (27.0 %), bleeding (9.8 %)), whereas 277
      patients (16.6 %) died for reasons not directly related with myelodysplastic
      syndromes (MDS), including 132 patients with cardiac failure, 77 non-disease
      related reasons, 23 patients with solid tumors, and 45 patients with possibly
      disease-related causes like hemochromatosis. Correlation with IPSS, IPSS-R, and
      WPSS categories showed a proportional increase of disease-related causes of death
      with increasing IPSS/IPSS-R/WPSS risk category. Likewise, therapy-related MDS
      were associated with a higher percentage of disease-related causes of death than
      primary MDS. This reflects the increasing influence of the underlying disease on
      the cause of death with increasing aggressiveness of the disease. 

PMID- 27025508
TI  - Central nervous system prophylaxis with intrathecal liposomal cytarabine in a
      subset of high-risk patients with diffuse large B-cell lymphoma receiving first
      line systemic therapy in a prospective trial.
AB  - The dissemination in the central nervous system (CNS) is an uncommon but fatal
      complication occurring in patients with diffuse large B-cell lymphoma (DLBCL).
      Standard prophylaxis has been demonstrated to reduce CNS relapse and improve
      survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated
      drug levels in the cerebrospinal fluid for an extended period of time. Data on
      the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients
      with DLBCL are still insufficient. The objective of the present study was to
      evaluate the effectiveness and safety of the prophylaxis with IT liposomal
      cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were
      included in a trial of first line systemic therapy with 6 cycles of dose-dense R
      CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to
      have risk factors for CNS involvement, defined as follows: >30 % bone marrow
      infiltration, testes infiltration, retroperitoneal mass >=10 cm, Waldeyer ring,
      or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was
      administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R
      CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were
      headache (one patient) and nausea/vomiting (one patient). With a median follow-up
      of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In
      conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS
      prophylaxis, causing few associated risks and little discomfort to patients with
      DLBCL. 

PMID- 27025509
TI  - A new 2DS.2RL Robertsonian translocation transfers stem rust resistance gene Sr59
      into wheat.
AB  - KEY MESSAGE: A new stem rust resistance gene Sr59 from Secale cereale was
      introgressed into wheat as a 2DS.2RL Robertsonian translocation. Emerging new
      races of the wheat stem rust pathogen (Puccinia graminis f. sp. tritici), from
      Africa threaten global wheat (Triticum aestivum L.) production. To broaden the
      resistance spectrum of wheat to these widely virulent African races, additional
      resistance genes must be identified from all possible gene pools. From the
      screening of a collection of wheat-rye (Secale cereale L.) chromosome
      substitution lines developed at the Swedish University of Agricultural Sciences,
      we described the line 'SLU238' 2R (2D) as possessing resistance to many races of
      P. graminis f. sp. tritici, including the widely virulent race TTKSK (isolate
      synonym Ug99) from Africa. The breakage-fusion mechanism of univalent chromosomes
      was used to produce a new Robertsonian translocation: T2DS.2RL. Molecular marker
      analysis and stem rust seedling assays at multiple generations confirmed that the
      stem rust resistance from 'SLU238' is present on the rye chromosome arm 2RL. Line
      TA5094 (#101) was derived from 'SLU238' and was found to be homozygous for the
      T2DS.2RL translocation. The stem rust resistance gene on chromosome 2RL arm was
      designated as Sr59. Although introgressions of rye chromosome arms into wheat
      have most often been facilitated by irradiation, this study highlights the
      utility of the breakage-fusion mechanism for rye chromatin introgression. Sr59
      provides an additional asset for wheat improvement to mitigate yield losses
      caused by stem rust.

PMID- 27025510
TI  - Do portfolios have a future?
AB  - While portfolios have seen an unprecedented surge in popularity, they have also
      become the subject of controversy: learners often perceive little gain from
      writing reflections as part of their portfolios; scholars question the ethics of
      such obligatory reflection; and students, residents, teachers and scholars alike
      condemn the bureaucracy surrounding portfolio implementation in competency-based
      education. It could be argued that mass adoption without careful attention to
      purpose and format may well jeopardize portfolios' viability in health sciences
      education. This paper explores this proposition by addressing the following three
      main questions: (1) Why do portfolios meet with such resistance from students and
      teachers, while educators love them?; (2) Is it ethical to require students to
      reflect and then grade their reflections?; (3) Does competency-based education
      empower or hamper the learner during workplace-based learning? Twenty-five years
      of portfolio reveal a clear story: without mentoring, portfolios have no future
      and are nothing short of bureaucratic hurdles in our competency-based education
      programs. Moreover, comprehensive portfolios, which are integrated into the
      curriculum and much more diverse in content than reflective portfolios, can serve
      as meaningful patient charts, providing doctor and patient with useful
      information to discuss well-being and treatment. In this sense, portfolios are
      also learner charts that comprehensively document progress in a learning
      trajectory which is lubricated by meaningful dialogue between learner and mentor
      in a trusting relationship to foster learning. If we are able to make such
      comprehensive and meaningful use of portfolios, then, yes, portfolios do have a
      bright future in medical education.

PMID- 27025511
TI  - Pharmacological evidence of neuro-pharmacological activity of Acacia tortilis
      leaves in mice.
AB  - Acacia tortilis is abundantly present in Saudi Arabia but its neuro
      pharmacological activity has not yet been evaluated. In this study, the
      antidepressant by Forced swim test, Anxiolytic (Light and Dark box) and sedative
      effects (by using Open Field) of Acacia leaves extract were evaluated in mice.
      Aqueous extracts of the Acacia tortilis leaves were prepared. Two different doses
      (400 and 800 mg/kg) of the extracts were administered to the mice orally (p.o.).
      In exploratory behavior, Acacia leave extract (800 mg/kg) produced a significant
      reduction (Veh, 91.00 +/- 5.26; Acacia 800 mg/kg, 46.33 +/- 3.24 p < 0.05)
      similar to the effect observed with chlorpromazine (CPZ) (Veh, 91.00 +/- 5.26;
      CPZ 1.0 mg/kg, 24.20 +/- 3.40 p < 0.05). A dose-dependent significant decrease in
      immobility time was also observed in mice and this effect was comparable to its
      positive control (Imipramine). However, In light-dark box test, mice treated with
      high dose (800 mg/kg/day) spent significant (p < 0.05) time on the light side of
      the light-dark box similar to positive control DZP. (Veh, 114.40 +/- 6.30 s;
      Acacia 800 mg/kg, 162.2 +/- 14.9; DZP 1.0 mg/kg, 184.20 +/- 9.24 p < 0.05). The
      present research propounded that Acacia tortilis leave extract contains some
      active ingredients with potential anxiolytic activity at low doses and
      antidepressant and sedative activity at high doses.

PMID- 27025512
TI  - Geometric changes in ventriculoaortic complex after transcatheter aortic valve
      replacement and its association with post-procedural prosthesis-patient mismatch:
      an intraprocedural 3D-TEE study.
AB  - AIMS: Prosthesis-patient mismatch (PPM) after transcatheter aortic valve
      replacement (TAVR) leads to increased mortality. However, its peri-procedural
      determinants remain unknown. We investigated geometric changes in aortic annulus
      (AoA) and left ventricular outflow tract (LVOT) during TAVR by three-dimensional
      transoesophageal echocardiography (3D-TEE) and its association with post
      procedural PPM. METHODS AND RESULTS: A total of 131 patients with severe aortic
      stenosis underwent intraprocedural 3D-TEE during balloon-expandable TAVR. The
      severity of PPM was graded using the indexed effective orifice area calculated by
      Doppler echocardiography at discharge, with moderate defined as >=0.65 and <=0.85
      cm2/m2 and severe defined as <0.65 cm2/m2. 3D planimetered AoA area decreased
      after TAVR (P< 0.001), whereas the LVOT increased (P= 0.004). The eccentricity of
      both AoA and LVOT decreased after TAVR (both, P< 0.001). At discharge, the
      incidence of overall and severe PPM was 44 and 12%, respectively. Patients with
      PPM had a larger body surface area, smaller aortic valve area, and less frequent
      balloon dilation (all P< 0.05). Patients with PPM had a lower post-TAVR AoA
      area/pre-TAVR AoA area (91 +/- 8 vs. 95 +/- 7%, P= 0.001) than those without PPM.
      The post-TAVR AoA area/pre-TAVR AoA area was independently associated with
      overall PPM (odds ratio, 1.80; 95% CI, 1.06-3.05; P= 0.031) and severe PPM (odds
      ratio, 2.50; 95% CI, 1.05-5.36; P= 0.04). Additionally, a cut-off value of this
      ratio >86.3% had a sensitivity of 84% and a specificity of 44% for the prevention
      of severe PPM. CONCLUSION: 3D-TEE can evaluate geometric changes in AoA and LVOT
      during balloon-expandable TAVR and predicts post-procedural PPM.

PMID- 27025514
TI  - Right from the heart: survivors of childhood cancer and the right ventricle.

PMID- 27025513
TI  - CMR assessment of the left ventricle apical morphology in subjects with
      unexplainable giant T-wave inversion and without apical wall thickness >=15 mm.
AB  - AIMS: Patients with unexplainable giant T-wave inversion in the precordial leads
      and apical wall thickness <15 mm have been reported. These patients cannot be
      diagnosed as apical hypertrophic cardiomyopathy (AHCM) according to the current
      criteria. The objective of this study was to evaluate the apical morphological
      features of this type of patients using cardiac magnetic resonance. METHODS AND
      RESULTS: Institutional ethics approval and written informed consent were
      obtained. A total of 60 subjects with unexplainable giant T-wave inversion and 76
      healthy volunteers were prospectively enrolled in the study. The segmented left
      ventricular (LV) wall thickness was measured according to the American Heart
      Association 17-segmented model. The apical angle (apA) as well as the regional
      variations in LV wall thickness was analysed. Considerable variation in LV wall
      thickness in normals was observed with progressive thinning from the base to apex
      (male and female, P < 0.01). The apical thickness of subjects with giant T-wave
      inversion was 8.10 +/- 1.67 mm in male, which is thicker than that of controls
      (4.14 +/- 1.17 mm, P < 0.01). In female, the apical thickness was also
      significantly different from controls (5.85 +/- 2.16 vs. 2.99 +/- 0.65 mm, P <
      0.01). Compared with normals, the apA decreased significantly in male (87.44 +/-
      13.86 vs.115.03 +/- 9.90 degrees , P < 0.01) and female (90.69 +/- 8.84 vs.
      110.07 +/- 13.58 degrees , P < 0.01) subjects, respectively. CONCLUSION: Although
      the absolute thickness of apical wall was below the current diagnostic criteria
      of AHCM, the apical morphological features of subjects with unexplainable giant T
      wave inversion were significantly different from normals. Whether these subjects
      should be included into a preclinical scope of AHCM needs further investigations.

PMID- 27025515
TI  - Understanding the mechanism for branch pulmonary artery stenosis after the
      arterial switch operation for transposition of the great arteries.
AB  - AIMS: The pathophysiology of branch pulmonary artery (PA) stenosis after the
      arterial switch operation, most commonly on the left, is incompletely understood.
      This study examines factors associated with left PA (LPA) obstruction. METHODS
      AND RESULTS: Cardiac magnetic resonance (CMR) imaging studies performed in
      patients after arterial switch operation (ASO) were retrospectively analysed.
      Blood flow was measured in both branch PAs and neo-pulmonary root position in
      relation to the aorta was expressed as an angle, relative to a line connecting
      the sternum and the spine. Sixty-six patients were included for analysis. Seventy
      per cent (n = 46) had balanced pulmonary blood flow, 28% (n = 18) had decreased
      flow to the left, and 2% (n = 2) had decreased flow to the right lung. LPA area
      indexed to body surface area (BSA) was smaller than RPA area (62 +/- 37 vs. 120
      +/- 64 mm2/m2, P < 0.0001). Patients with reduced LPA flow were more likely to
      have required pulmonary arterioplasty at the time of ASO (17 vs. 2%, P = 0.04)
      and had a larger aortic root diameter (25 +/- 7 vs. 22 +/- 5 mm2/m2, P = 0.01).
      Greater rightward orientation of the neo-pulmonary root correlated inversely with
      LPA cross-sectional area (r = -0.39, P = 0.001) but not with LPA flow. Aortic
      root diameter correlated inversely with LPA flow (r = -0.43, P = 0.0004) but not
      with LPA cross-sectional area (P = 0.32). Patients with a rightward neo-pulmonary
      root and/or a dilated aortic root in the upper quartile range had a smaller LPA
      area (53 vs. 73 mm2/m2, P = 0.04) and less pulmonary blood flow (41 vs. 46%, P =
      0.02) compared with patients without those risk factors. CONCLUSIONS: Neo
      pulmonary to neo-aortic geometry as well as post-operative compression of the LPA
      by an enlarged aorta impact LPA size and perfusion of the left lung.

PMID- 27025516
TI  - Analysis of Tetracyclines in Medicated Feed for Food Animal Production by HPLC
      MS/MS.
AB  - The use of medicated feed is a common practice in animal food production to
      improve animal health. Tetracyclines and beta-Lactams are the groups that are
      most frequently added to this type of feed. The measurement of the concentration
      of the analytes in these types of samples is sometimes due to the matrix
      characteristic, and manufacturers are demanding fast, precise and reproducible
      methods. A rapid confirmatory method based on a simple extraction protocol using
      acidified methanol and followed by high performance liquid chromatography coupled
      to a tandem mass spectrometer for the quantification of four tetracyclines in
      feed is presented. Validation was performed following the guidelines of Decision
      2002/657/EC. Results indicated that the four tetracyclines can be identified and
      quantified in a concentration range between 50 and 500 mg/kg with recoveries
      between 84% and 109% and RSD for precision under reproducible conditions between
      12% and 16%. Satisfactory results were also obtained with interlaboratory studies
      and by comparing the method with an HPLC-Fluorescent method. 

PMID- 27025517
TI  - Cost Reduction of Inhaled Tobramycin by Use of Preservative-Free Intravenous
      Tobramycin Given via Inhalation.
AB  - This study evaluates drug cost outcomes related to automatic therapeutic
      substitution of branded tobramycin solution for inhalation (TOBI((r))) with
      inhaled generic preservative-free intravenous tobramycin (PFIT). A retrospective
      single-center evaluation of inhaled tobramycin use from 2008 through 2012 was
      performed. Number of doses dispensed and acquisition costs were obtained. Hourly
      wage data was acquired, pharmacy production costs were estimated and total cost
      savings calculated. Days of therapy (DOTs) were determined for each year. Quality
      assurance and safety data was collected. In 2008, TOBI((r)) drug costs and doses
      dispensed were $118,665 and 1769, respectively. Following implementation of the
      interchange in May 2009, TOBI((r)) utilization ceased. PFIT costs in 2010 through
      2012 averaged $34,775 annually and TOBI((r)) cost-avoidance exceeded $94,000
      annually when accounting for pharmacy production costs, which were determined to
      be at most $5.28 per dose. The maximum estimated pharmacy production cost ranged
      from $8812 to $11,299 annually. PFIT doses dispensed exceeded 1650 each year and
      annual DOTs ranged from 815 to 1069. The 40-month savings were calculated to be
      $374,706. Quality assurance and safety data identified one patient who refused
      PFIT due to odor complaints and one patient who was inappropriately administered
      a dose orally. Therapeutic substitution of TOBI((r)) with PFIT can produce
      immediate and sustained savings with an acceptable safety profile. 

PMID- 27025518
TI  - Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections.
AB  - Most bacteria attach to surfaces where they form a biofilm, cells embedded in a
      complex matrix of polymers. Cells in biofilms are much better protected against
      noxious agents than free-living cells. As a consequence it is very difficult to
      control pathogens with antibiotics in biofilm infections and novel targets are
      urgently needed. One approach aims at the communication between cells to form and
      to maintain a biofilm, a process called quorum-sensing. Water soluble small-sized
      molecules mediate this process and a number of antagonists of these compounds
      have been found. In this review natural compounds and synthetic drugs which do
      not interfere with the classical quorum-sensing compounds are discussed. For some
      of these compounds the targets are still not known, but others interfere with the
      formation of exopolysaccharides, virulence factors, or cell wall synthesis or
      they start an internal program of biofilm dispersal. Some of their targets are
      more conserved among pathogens than the receptors for quorum sensing autoinducers
      mediating quorum-sensing, enabling a broader application of the drug. The broad
      spectrum of mechanisms, the diversity of bioactive compounds, their activity
      against several targets, and the conservation of some targets among bacterial
      pathogens are promising aspects for several clinical applications of this type of
      biofilm-controlling compound in the future. 

PMID- 27025519
TI  - Microarray Evaluation of Antimicrobial Resistance and Virulence of Escherichia
      coli Isolates from Portuguese Poultry.
AB  - The presence of antimicrobial resistance and virulence factors of 174 Escherichia
      coli strains isolated from healthy Portuguese Gallus gallus was evaluated.
      Resistance profiles were determined against 33 antimicrobials by microbroth
      dilution. Resistance was prevalent for tetracycline (70%) and ampicillin (63%).
      Extended-spectrum beta-lactamase (ESBL) phenotype was observed in 18% of the
      isolates. Multidrug resistance was found in 56% of isolates. A subset of 74
      isolates were screened by DNA microarrays for the carriage of 88 antibiotic
      resistance genes and 62 virulence genes. Overall, 37 different resistance genes
      were detected. The most common were tet(A) (72%), blaTEM (68%), and sul1 (47%),
      while 21% isolates harbored an ESBL gene (blaCTX-M group 1, group 2, or group 9).
      Of these, 96% carried the increased serum survival (iss) virulence gene, while
      89% presented the enterobactin siderophore receptor protein (iroN), 70% the
      temperature-sensitive hemagglutinin (tsh), and 68% the long polar fimbriae (lpfA)
      virulence genes associated with extraintestinal pathogenic E. coli. In
      conclusion, prevalence of antibiotic resistant E. coli from the microbiota of
      Portuguese chickens was high, including to extended spectrum cephalosporins. The
      majority of isolates seems to have the potential to trigger extraintestinal human
      infection due to the presence of some virulence genes. However, the absence of
      genes specific for enteropathogenic E. coli reduces the risk for human intestinal
      infection. 

PMID- 27025520
TI  - A Review of Quality Measures for Assessing the Impact of Antimicrobial
      Stewardship Programs in Hospitals.
AB  - The growing problem of antimicrobial resistance (AMR) has led to calls for
      antimicrobial stewardship programs (ASP) to control antibiotic use in healthcare
      settings. Key strategies include prospective audit with feedback and
      intervention, and formulary restriction and preauthorization. Education,
      guidelines, clinical pathways, de-escalation, and intravenous to oral conversion
      are also part of some programs. Impact and quality of ASP can be assessed using
      process or outcome measures. Outcome measures are categorized as microbiological,
      patient or financial outcomes. The objective of this review was to provide an
      overview of quality measures for assessing ASP and the reported impact of ASP in
      peer-reviewed studies, focusing particularly on patient outcomes. A literature
      search of papers published in English between 1990 and June 2015 was conducted in
      five databases using a combination of search terms. Primary studies of any design
      were included. A total of 63 studies were included in this review. Four studies
      defined quality metrics for evaluating ASP. Twenty-one studies assessed the
      impact of ASP on antimicrobial utilization and cost, 25 studies evaluated impact
      on resistance patterns and/or rate of Clostridium difficile infection (CDI).
      Thirteen studies assessed impact on patient outcomes including mortality, length
      of stay (LOS) and readmission rates. Six of these 13 studies reported non
      significant difference in mortality between pre- and post-ASP intervention, and
      five reported reductions in mortality rate. On LOS, six studies reported shorter
      LOS post intervention; a significant reduction was reported in one of these
      studies. Of note, this latter study reported significantly (p < 0.001) higher
      unplanned readmissions related to infections post-ASP. Patient outcomes need to
      be a key component of ASP evaluation. The choice of metrics is influenced by data
      and resource availability. Controlling for confounders must be considered in the
      design of evaluation studies to adequately capture the impact of ASP and it is
      important for unintended consequences to be considered. This review provides a
      starting point toward compiling standard outcome metrics for assessing ASP. 

PMID- 27025521
TI  - Controversies in Antimicrobial Stewardship: Focus on New Rapid Diagnostic
      Technologies and Antimicrobials.
AB  - Antimicrobial stewardship programs (ASPs) are challenged with ensuring
      appropriate antimicrobial use while minimizing expenditures. ASPs have
      consistently demonstrated improved patient outcomes and significant cost
      reductions but are continually required to justify the costs of their existence
      and interventions due to the silo mentality often adopted by hospital
      administrators. As new technologies and antimicrobials emerge, ASPs are in a
      constant tug-of-war between providing optimal clinical outcomes and ensuring cost
      containment. Additionally, robust data on cost-effectiveness of new rapid
      diagnostic technologies and antimicrobials with subsequent ASP interventions to
      provide justification are lacking. As the implementation of an ASP will soon be
      mandatory for acute care hospitals in the United States, ASPs must find ways to
      justify novel interventions to align themselves with healthcare administrators.
      This review provides a framework for the justification of implementing a rapid
      diagnostic test or adding a new antimicrobial to formulary with ASP intervention,
      reviews approaches to demonstrating cost-effectiveness, and proposes methods for
      which ASPs may reduce healthcare expenditures via alternative tactics. 

PMID- 27025522
TI  - Evaluation of a Computerized Decision Support Intervention to Decrease Use of
      Anti-Pseudomonal Carbapenems in Penicillin Allergic Patients.
AB  - Allergies to beta-lactam antibiotics are commonly documented in hospitalized
      patients; however, true allergy is uncommon. Cross-reactivity rates for advanced
      generation cephalosporins and carbapenems are low; particularly for patients
      without a history of symptoms consistent with type 1 hypersensitivity. We
      observed that providers preferentially prescribed antipseudomonal carbapenems
      (APC) over advanced generation cephalosporins for patients with beta-lactam
      allergy history, including those with low risk for antimicrobial-resistant
      infections. Information was inserted into the computerized decision support
      system (CDSS) to aid clinicians in assessing beta-lactam cross-reactivity risk
      and selecting appropriate therapy. A retrospective evaluation was conducted in a
      small hospital to assess the impact of the CDSS changes in APC prescribing.
      Inpatients (n = 68) who received at least one APC dose during hospitalization
      over a 13 month pre-intervention period were compared to inpatients who received
      an APC during the 15 month post-intervention period (n = 59) for documented APC
      indications and beta-lactam allergy history. APC initiations were measured and
      corrected per 1000 patient-days; interrupted time-series analysis was performed
      to assess changes in use before and after implementation. Aggregate monthly APC
      initiations decreased from 7.01 to 6.14 per 1000 patient-days after the
      implementation (p = 0.03). Post-intervention APC initiations for patients with
      low-risk beta-lactam histories decreased from 92% to 83% (p = 0.17). No adverse
      events were observed in patients with low-risk beta-lactam histories. The
      intervention was associated with a reduction in APC initiations. 

PMID- 27025523
TI  - Antimicrobial Stewardship for a Geriatric Behavioral Health Population.
AB  - Antimicrobial resistance is a growing public health concern. Antimicrobial
      stewardship and multi-disciplinary intervention can prevent inappropriate
      antimicrobial use and improve patient care. Special populations, especially older
      adults and patients with mental health disorders, can be particularly in need of
      such intervention. The purpose of this project was to assess the impact of
      pharmacist intervention on appropriateness of antimicrobial prescribing on a
      geriatric psychiatric unit (GPU). Patients >=18 years old prescribed oral
      antibiotics during GPU admission were included. Antimicrobial appropriateness was
      assessed pre- and post-pharmacist intervention. During the six-month pre- and
      post-intervention phase, 63 and 70 patients prescribed antibiotics were
      identified, respectively. Subjects in the post-intervention group had
      significantly less inappropriate doses for indication compared to the pre
      intervention group (10.6% vs. 23.9%, p = 0.02), and significantly less
      antibiotics prescribed for an inappropriate duration (15.8% vs. 32.4%, p < 0.01).
      There were no significant differences for use of appropriate drug for indication
      or appropriate dose for renal function between groups. Significantly more
      patients in the post intervention group had medications prescribed with
      appropriate dose, duration, and indication (51% vs. 66%, p = 0.04). Pharmacist
      intervention was associated with decreased rates of inappropriate antimicrobial
      prescribing on a geriatric psychiatric unit. 

PMID- 27025525
TI  - Identification of a Fragment-Based Scaffold that Inhibits the Glycosyltransferase
      WaaG from Escherichia coli.
AB  - WaaG is a glycosyltransferase that is involved in the biosynthesis of
      lipopolysaccharide in Gram-negative bacteria. Inhibitors of WaaG are highly
      sought after as they could be used to inhibit the biosynthesis of the core region
      of lipopolysaccharide, which would improve the uptake of antibiotics. Herein, we
      establish an activity assay for WaaG using (14)C-labeled UDP-glucose and LPS
      purified from a ?waaG strain of Escherichia coli. We noted that addition of the
      lipids phosphatidylglycerol (PG) and cardiolipin (CL), as well as the detergent 3
      [(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) increased
      activity. We then use the assay to determine if three molecular scaffolds, which
      bind to WaaG, could inhibit its activity in vitro. We show that 4-(2-amino-1,3
      thiazol-4-yl)phenol inhibits WaaG (IC50 1.0 mM), but that the other scaffolds do
      not. This study represents an important step towards an inhibitor of WaaG by
      fragment-based lead discovery. 

PMID- 27025526
TI  - Treatment Modalities and Antimicrobial Stewardship Initiatives in the Management
      of Intra-Abdominal Infections.
AB  - Antimicrobial stewardship programs (ASPs) focus on improving the utilization of
      broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram
      positive and Gram negative pathogens. Hospital admission for both medical and
      surgical intra-abdominal infections (IAIs) commonly results in the empiric use of
      broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase
      inhibitors, and carbapenems that can select for resistant organisms. This review
      will discuss the management of uncomplicated and complicated IAIs as well as
      highlight stewardship initiatives focusing on the proper use of broad spectrum
      antibiotics. 

PMID- 27025528
TI  - A Multi-Faceted Approach of One Teaching Hospital NHS Trust during the
      Clostridium difficile Epidemic-Antibiotic Management and Beyond.
AB  - The incidence of Clostridium difficile infection (CDI) in the UK rose
      dramatically during the early years of this century, in part associated with the
      emergence of the hyper-virulent ribotype 027 strain. The University Hospitals of
      Leicester (UHL), a 2000-bed acute UK NHS Trust, implemented a number of
      interventions, which led to an 80% reduction in new cases over a twelve month
      period. Changes were introduced as a result of collaboration between the
      Infection Prevention team, the departments of Microbiology and Infectious
      Diseases, and with the support of the Trust Executive. These strategies are
      described in detail and included; implementation of antimicrobial stewardship,
      specific hygiene and cleaning measures, the introduction of a care pathway form
      for all infected patients, the opening of an isolation ward for patients with
      CDI, strengthened organisation and clinical management, and rigorous attention to
      education within the Trust. The implementations described are of continued
      relevance in the face of new infection challenges, such as the increasing
      incidence of multi-drug resistant organisms. 

PMID- 27025529
TI  - Controlling electron emission from the photoactive yellow protein chromophore by
      substitution at the coumaric acid group.
AB  - Understanding how the interactions between a chromophore and its surrounding
      protein control the function of a photoactive protein remains a challenge. Here,
      we present the results of photoelectron spectroscopy measurements and quantum
      chemistry calculations aimed at investigating how substitution at the coumaryl
      tail of the photoactive yellow protein chromophore controls competing relaxation
      pathways following photoexcitation of isolated chromophores in the gas phase with
      ultraviolet light in the range 350-315 nm. The photoelectron spectra are
      dominated by electrons resulting from direct detachment and fast detachment from
      the 2(1)pipi* state but also have a low electron kinetic energy component arising
      from autodetachment from lower lying electronically excited states or thermionic
      emission from the electronic ground state. We find that substituting the hydrogen
      atom of the carboxylic acid group with a methyl group lowers the threshold for
      electron detachment but has very little effect on the competition between the
      different relaxation pathways, whereas substituting with a thioester group raises
      the threshold for electron detachment and appears to 'turn off' the competing
      electron emission processes from lower lying electronically excited states. This
      has potential implications in terms of tuning the light-induced electron donor
      properties of photoactive yellow protein.

PMID- 27025527
TI  - Glycosyltransferases and Transpeptidases/Penicillin-Binding Proteins: Valuable
      Targets for New Antibacterials.
AB  - Peptidoglycan (PG) is an essential macromolecular sacculus surrounding most
      bacteria. It is assembled by the glycosyltransferase (GT) and transpeptidase (TP)
      activities of multimodular penicillin-binding proteins (PBPs) within multiprotein
      complex machineries. Both activities are essential for the synthesis of a
      functional stress-bearing PG shell. Although good progress has been made in terms
      of the functional and structural understanding of GT, finding a clinically useful
      antibiotic against them has been challenging until now. In contrast, the TP/PBP
      module has been successfully targeted by beta-lactam derivatives, but the
      extensive use of these antibiotics has selected resistant bacterial strains that
      employ a wide variety of mechanisms to escape the lethal action of these
      antibiotics. In addition to traditional beta-lactams, other classes of molecules
      (non-beta-lactams) that inhibit PBPs are now emerging, opening new perspectives
      for tackling the resistance problem while taking advantage of these valuable
      targets, for which a wealth of structural and functional knowledge has been
      accumulated. The overall evidence shows that PBPs are part of multiprotein
      machineries whose activities are modulated by cofactors. Perturbation of these
      systems could lead to lethal effects. Developing screening strategies to take
      advantage of these mechanisms could lead to new inhibitors of PG assembly. In
      this paper, we present a general background on the GTs and TPs/PBPs, a survey of
      recent issues of bacterial resistance and a review of recent works describing new
      inhibitors of these enzymes. 

PMID- 27025530
TI  - Good results of surgery for renal cell carcinoma depend on early diagnosis. The
      need for an extensive screening program.
AB  - AIM: The aim of our study was to assess the value of several prognostic factors
      for patients with clear cell renal carcinoma without distant metastases (M0) who
      underwent surgery in our Department from 1980 to 2010. MATERIAL OF STUDY: We
      analyzed131 consecutive patients with clear cell renal carcinoma who had
      nephrectomy and extended lymph node dissection from 1980 to 2010 were reviewed.
      Free from cancer survivals were correlated to several prognostic factors
      including preoperative blood cell count, tumour cellular differentiation and
      stage of the disease. RESULTS: In our study we confirmed the importance of the
      stage of the tumour, in particular of the T, as prognostic factor. Survival was
      strictly correlated to the stage of the disease: 10 year cancer free survival was
      100% in patients with T1, 83% in patients with T2 N0 and 34% for patients with
      T3N0. No improvement of results was noted in the last years, due to unchanged
      proportion of early diagnosis. DISCUSSION: Long term survival after surgery for
      clear cell renal carcinoma depends mainly on the histology type of the tumour and
      on the stage of the disease. Renal carcinoma does not respond to radio and
      standard chemotherapy and surgery represents the only effective cure. CONCLUSION:
      Surgery at earlier stages is essential to improve results in patients with renal
      carcinoma. Earlier diagnosis at the present time is the best possibility to
      improve results, with the need for extensive use of screening ultrasound test.
      KEY WORDS: Lymph node dissection in renal carcinoma, Renal carcinoma, Results of
      surgery for renal carcinoma.

PMID- 27025531
TI  - Experimental Psychology.

PMID- 27025533
TI  - The Moderating Impact of Distal Regularities on the Effect of Stimulus Pairings.
AB  - Throughout much of the past century psychologists have focused their attention on
      a seemingly simple question: How do people come to like or dislike stimuli in the
      environment? Evaluative Conditioning (EC) - a change in liking due to the pairing
      of stimuli - has been offered as one avenue through which novel preferences may
      be formed and existing ones altered. In the current article, we offer a new look
      at EC from the perspective of Contextual Behavioral Science (CBS) and, more
      specifically, Relational Frame Theory (RFT). We briefly review the EC literature,
      introduce Contextual Behavioral Science (CBS), Relational Frame Theory (RFT), and
      then describe a behavioral phenomenon known as arbitrarily applicable relational
      responding (AARR). Afterwards, we examine the relationship between EC and AARR.
      This novel perspective offers ways to organize existing as well as predict new EC
      effects, contributes to debates on "genuine" EC, human versus nonhuman EC, and
      further facilitates the development and refinement of cognitive theories of EC. 

PMID- 27025532
TI  - Single- and Dual-Process Models of Biased Contingency Detection.
AB  - Decades of research in causal and contingency learning show that people's
      estimations of the degree of contingency between two events are easily biased by
      the relative probabilities of those two events. If two events co-occur
      frequently, then people tend to overestimate the strength of the contingency
      between them. Traditionally, these biases have been explained in terms of
      relatively simple single-process models of learning and reasoning. However, more
      recently some authors have found that these biases do not appear in all dependent
      variables and have proposed dual-process models to explain these dissociations
      between variables. In the present paper we review the evidence for dissociations
      supporting dual-process models and we point out important shortcomings of this
      literature. Some dissociations seem to be difficult to replicate or poorly
      generalizable and others can be attributed to methodological artifacts. Overall,
      we conclude that support for dual-process models of biased contingency detection
      is scarce and inconclusive. 

PMID- 27025534
TI  - Exploring the Subjective Feeling of Fluency.
AB  - According to the processing fluency theory, higher ease of processing a stimulus
      leads to higher feelings of fluency and more positive evaluations. However, it is
      unclear whether feelings of fluency are positive or an unspecific activation and
      whether feelings of fluency are directly attributed to the stimulus even without
      much positive feelings. In two experiments, we tested how variations in the ease
      of processing influenced feelings of fluency and affect, in terms of evaluations
      (Exp. 1) and physiological responses (Exp. 2). Higher feelings of fluency were
      associated with more positive stimulus ratings and did not affect stimulus
      arousal ratings, but perceivers' feelings showed higher felt arousal ratings and
      left felt valence ratings unaffected. Physiological indices only showed small
      effects of a subtle positive reaction. These findings show that feelings of
      fluency can be sources of positive object evaluations, but do not affect one's
      own positive feelings. 

PMID- 27025535
TI  - The Influence of Presentation Order on Category Transfer.
AB  - This study of supervised categorization shows how different kinds of category
      representations are influenced by the order in which training examples are
      presented. We used the well-studied 5-4 category structure of Medin and Schaffer
      (1978) , which allows transfer of category learning to new stimuli to be
      discriminated as a function of rule-based or similarity-based category knowledge.
      In the rule-based training condition (thought to facilitate the learning of
      abstract logical rules and hypothesized to produce rule-based classification),
      items were grouped by subcategories and randomized within each subcategory. In
      the similarity-based training condition (thought to facilitate associative
      learning and hypothesized to produce exemplar classification), transitions
      between items within the same category were determined by their featural
      similarity and subcategories were ignored. We found that transfer patterns
      depended on whether the presentation order was similarity-based, or rule-based,
      with the participants particularly capitalizing on the rule-based order. 

PMID- 27025536
TI  - Evaluative Priming in the Pronunciation Task.
AB  - We replicated and extended a study by Spruyt and Hermans (2008) in which picture
      primes engendered an evaluative-priming effect on the pronunciation of target
      words. As preliminary steps, we assessed data reproducibility of the original
      study, conducted Pilot Study I to identify highly semantically related prime
      target pairs, reanalyzed the original data excluding such pairs, conducted Pilot
      Study II to demonstrate that we can replicate traditional associative priming
      effects in the pronunciation task, and conducted Pilot Study III to generate
      relatively unrelated sets of prime pictures and target words. The main study
      comprised three between-participants conditions: (1) a close replication of the
      original study, (2) the same condition excluding highly related prime-target
      pairs, and (3) a condition based on the relatively unrelated sets of prime
      pictures and target words developed in Pilot Study III. There was little evidence
      for an evaluative priming effect independent of semantic relatedness. 

PMID- 27025537
TI  - 3D printing of liquid metals as fugitive inks for fabrication of 3D microfluidic
      channels.
AB  - This paper demonstrates a simple method to fabricate 3D microchannels and
      microvasculature at room temperature by direct-writing liquid metal as a
      sacrificial template. The formation of a surface oxide skin on the low-viscosity
      liquid metal stabilizes the shape of the printed metal for planar and out-of
      plane structures. The printed structures can be embedded in a variety of soft
      (e.g. elastomeric) and rigid (e.g. thermoset) polymers. Both acid and
      electrochemical reduction are capable of removing the oxide skin that forms on
      the metal, which destabilizes the ink so that it withdraws from the encapsulating
      material due to capillary forces, resulting in nearly full recovery of the
      fugitive ink at room temperature. Whereas conventional fabrication procedures
      typically confine microchannels to 2D planes, the geometry of the printed
      microchannels can be varied from a simple 2D network to complex 3D architectures
      without using lithography. The method produces robust monolithic structures
      without the need for any bonding or assembling techniques that often limit the
      materials of construction of conventional microchannels. Removing select portions
      of the metal leaves behind 3D metal features that can be used as antennas,
      interconnects, or electrodes for interfacing with lab-on-a-chip devices. This
      paper describes the capabilities and limitations of this simple process.

PMID- 27025538
TI  - X-ray Absorption Spectroscopy Study of the Effect of Rh doping in Sr2IrO4.
AB  - We investigate the effect of Rh doping in Sr2IrO4 using X-ray absorption
      spectroscopy (XAS). We observed appearance of new electron-addition states with
      increasing Rh concentration (x in Sr2Ir1-xRhxO4) in accordance with the concept
      of hole doping. The intensity of the hole-induced state is however weak,
      suggesting weakness of charge transfer (CT) effect and Mott insulating ground
      states. Also, Ir Jeff = 1/2 upper Hubbard band shifts to lower energy as x
      increases up to x = 0.23. Combined with optical spectroscopy, these results
      suggest a hybridisation-related mechanism, in which Rh doping can weaken the (Ir
      Jeff = 1/2)-(O 2p) orbital hybridisation in the in-planar Rh-O-Ir bond networks.

PMID- 27025539
TI  - Partial Nephrectomy for Small Renal Masses: Do Teaching and Nonteaching
      Institutions Adhere to Guidelines Equally?
AB  - INTRODUCTION: The American Urological Association (AUA) guidelines recommend
      partial nephrectomy (PN) as the gold standard for treatment of small renal masses
      (SRMs). This study examines the change in utilization of partial and radical
      nephrectomies at teaching and nonteaching institutions from 2003 to 2012.
      MATERIALS AND METHODS: The data sample for this study came from the Healthcare
      Cost and Utilization Project Nationwide Inpatient Sample from 2003 to 2012.
      International Classification of Diseases, Ninth Revision and Clinical
      Modification codes were used to identify patients undergoing PN and radical
      nephrectomy for renal masses limited to the renal parenchyma. Teaching hospitals
      were defined, but not limited to any institution with an American Medical
      Association-approved residency program. Linear regression, bivariate,
      multivariate, and odds ratio analysis were used to demonstrate statistical
      significance. RESULTS: 39,685 patients were identified in teaching hospitals, and
      22,239 were identified in nonteaching hospitals. Prior to the 2009 AUA
      guidelines, cumulative rates of PN were 33% vs 20% in teaching vs nonteaching
      hospitals (p < 0.0001) compared with postguideline rates of 48% vs 33% in
      teaching vs nonteaching hospitals (p < 0.0001). CONCLUSIONS: During the 10-year
      study period, the use of PN to treat SRMs has significantly increased in both
      teaching hospitals and in nonacademic centers; however, these changes are
      occurring at a slower rate in nonteaching hospitals.

PMID- 27025540
TI  - Usability Testing of a Complex Clinical Decision Support Tool in the Emergency
      Department: Lessons Learned.
AB  - BACKGROUND: As the electronic health record (EHR) becomes the preferred
      documentation tool across medical practices, health care organizations are
      pushing for clinical decision support systems (CDSS) to help bring clinical
      decision support (CDS) tools to the forefront of patient-physician interactions.
      A CDSS is integrated into the EHR and allows physicians to easily utilize CDS
      tools. However, often CDSS are integrated into the EHR without an initial phase
      of usability testing, resulting in poor adoption rates. Usability testing is
      important because it evaluates a CDSS by testing it on actual users. This paper
      outlines the usability phase of a study, which will test the impact of
      integration of the Wells CDSS for pulmonary embolism (PE) diagnosis into a large
      urban emergency department, where workflow is often chaotic and high stakes
      decisions are frequently made. We hypothesize that conducting usability testing
      prior to integration of the Wells score into an emergency room EHR will result in
      increased adoption rates by physicians. OBJECTIVE: The objective of the study was
      to conduct usability testing for the integration of the Wells clinical prediction
      rule into a tertiary care center's emergency department EHR. METHODS: We
      conducted usability testing of a CDS tool in the emergency department EHR. The
      CDS tool consisted of the Wells rule for PE in the form of a calculator and was
      triggered off computed tomography (CT) orders or patients' chief complaint. The
      study was conducted at a tertiary hospital in Queens, New York. There were seven
      residents that were recruited and participated in two phases of usability
      testing. The usability testing employed a "think aloud" method and "near-live"
      clinical simulation, where care providers interacted with standardized patients
      enacting a clinical scenario. Both phases were audiotaped, video-taped, and had
      screen-capture software activated for onscreen recordings. RESULTS: Phase I: Data
      from the "think-aloud" phase of the study showed an overall positive outlook on
      the Wells tool in assessing a patient for a PE diagnosis. Subjects described the
      tool as "well-organized" and "better than clinical judgment". Changes were made
      to improve tool placement into the EHR to make it optimal for decision-making,
      auto-populating boxes, and minimizing click fatigue. Phase II: After
      incorporating the changes noted in Phase 1, the participants noted tool
      improvements. There was less toggling between screens, they had all the clinical
      information required to complete the tool, and were able to complete the patient
      visit efficiently. However, an optimal location for triggering the tool remained
      controversial. CONCLUSIONS: This study successfully combined "think-aloud"
      protocol analysis with "near-live" clinical simulations in a usability evaluation
      of a CDS tool that will be implemented into the emergency room environment. Both
      methods proved useful in the assessment of the CDS tool and allowed us to refine
      tool usability and workflow.

PMID- 27025541
TI  - Endoscopic management of a gastrocolonic fistula.

PMID- 27025542
TI  - Successful endoscopic management of a malignant ileovesicular fistula.

PMID- 27025543
TI  - An uncommon cause of chronic upper GI bleeding.

PMID- 27025544
TI  - Endoscopic salvage of errantly deployed lumen-apposing metal stents.

PMID- 27025545
TI  - Endoscopic removal of a mesh penetrating into the esophagus using overtube
      assisted endoscopy, fully covered metal stent, and over-the-scope clip.

PMID- 27025546
TI  - Smart surface coating of drug nanoparticles with cross-linkable polyethylene
      glycol for bio-responsive and highly efficient drug delivery.
AB  - Many drug molecules can be directly used as nanomedicine without the requirement
      of any inorganic or organic carriers such as silica and liposome nanostructures.
      This new type of carrier-free drug nanoparticles (NPs) has great potential in
      clinical treatment because of its ultra-high drug loading capacity and
      biodegradability. For practical applications, it is essential for such
      nanomedicine to possess robust stability and minimal premature release of
      therapeutic molecules during circulation in the blood stream. To meet this
      requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic
      polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG
      molecules can be cross-linked on the surface of the NPs to endow them with
      greater stability and the cross-link is sensitive to intracellular environment
      for bio-responsive drug release. With this elegant design, our experimental
      results show that the liberation of DOX from DOX-cross-linked PEG NPs is
      dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX
      release profile can be controlled by tuning the concentration of the reducing
      agent to break the cross-link between PEG molecules. More importantly, in vivo
      studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood
      circulation half-life (>4 h) and intense accumulation in tumor areas, enabling
      effective anti-cancer therapy. We expect this work will provide a powerful
      strategy for stabilizing carrier-free nanomedicines and pave the way to their
      successful clinical applications in the future. 

PMID- 27025547
TI  - Hypertensive pathologies and egg donation pregnancies: Results of a large
      comparative cohort study.
AB  - OBJECTIVE: To determine whether egg donation (ED) pregnancies are at higher risk
      of pregnancy-induced hypertension (PIH) than those achieved by autologous
      assisted reproductive technology (ART; controls). DESIGN: Anonymous comparative
      observational matched cohort study. SETTING: Assisted reproductive technology
      centers. PATIENT(S): Two hundred seventeen ED and 363 control singleton
      pregnancies matched at 7-8 weeks (pregnancy date, parity, cycle type
      [fresh/frozen] and women's age). According to French practice, all women were
      under 45. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentage of PIH for
      ED versus controls. RESULT(S): The groups were comparable (mean age, 34.5). PIH
      was more frequent during ED pregnancies (17.8% vs. 5.3%), as was preeclampsia
      (11.2% vs. 2.8%) and eclampsia (1.8% vs. 0.0%). In multivariate analyses, PIH
      risk increased with ED (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.93
      7.97) and women's age (OR, 1.08; 95% CI, 1.00-1.16). No significant effect of
      previous pregnancies or cycle rank/type was observed. CONCLUSION(S): This study
      had sufficient power to detect doubling of the PIH rate. It was demonstrated that
      the risk of PIH was tripled for ED versus controls. Even in young women, ED is a
      risk factor for PIH. An immunological explanation seems most likely, that is, the
      fetus is fully allogeneic to its mother. This risk must be acknowledged to inform
      couples and provide careful pregnancy monitoring.

PMID- 27025548
TI  - Bacterial and fungal contamination risks in human oocyte and embryo
      cryopreservation: open versus closed vitrification systems.
AB  - OBJECTIVE: To study the contamination risk in open and closed vitrification
      devices for oocyte/embryo cryopreservation by evaluating the contaminants present
      (bacteria and fungi) in the thaw medium and in liquid nitrogen (LN) storage
      containers. DESIGN: Retrospective study. SETTING: Human reproduction unit.
      PATIENT(S): None. INTERVENTION(S): Retrospective study of vitrification device
      safety and LN sterility performed from July to October 2014. MAIN OUTCOME
      MEASURE(S): From each bank container, both open and closed vitrification devices,
      devitrification media and LN in the containers and as supplied by the company
      were evaluated for contaminants. An automated system and the corresponding
      susceptibility to antibiotics were used for bacteria identification. Fungus
      detection was performed by evaluating the colony morphology and their microscopic
      characteristics. RESULT(S): No bacteria or fungi were observed in any of the
      devitrification media regardless of the type of device used, nor in the LN
      supplied by the company. No fungi were observed in any of the LN samples tested.
      Stenotrophomonas maltophilia and Bacillus spp. were found in all oocyte/embryo
      bank LN containers. There was no relationship between the number of samples or
      the time that each container had been used and the presence of microbiologic
      contaminants in the LN. At the container's bottom, Acinetobacter lwoffii,
      Alcaligenes faecalis ssp. faecalis, and Sphingomonas paucimobilis were found.
      CONCLUSION(S): Bacteria cross-contamination may not occur in oocyte/embryo
      banking in either open or closed storage devices. However, microorganisms can
      survive in LN. The bacteria cross-contamination risk is no greater for open than
      for closed containers. Storage containers should be cleaned periodically owing to
      the risk of lost straws or small particles of contaminated material.

PMID- 27025549
TI  - Perversions with a twist.
AB  - Perversions connecting two helices with symmetric handedness are a common
      occurrence in nature, for example in tendrils. These defects can be found in our
      day life decorating ribbon gifts or when plants use tendrils to attach to a
      support. Perversions arise when clamped elastic filaments coil into a helical
      shape but have to conserve zero overall twist. We investigate whether other types
      of perversions exist and if they display different properties. Here we show
      mathematically and experimentally that a continuous range of different
      perversions can exist and present different geometries. Experimentally, different
      perversions were generated using micro electrospun fibres. Our experimental
      results also confirm that these perversions behave differently upon release and
      adopt different final configurations. These results also demonstrate that it is
      possible to control on demand the formation and shape of microfilaments, in
      particular, of electrospun fibres by using ultraviolet light. 

PMID- 27025550
TI  - Development and Pilot Evaluation of an Online Relapse-Prevention Program Based on
      Acceptance and Commitment Therapy for Chronic Pain Patients.
AB  - BACKGROUND: A significant number of chronic pain patients experience a decline in
      therapeutic effects after rehabilitation. As face-to-face contacts with health
      care professionals are not always feasible after treatment, new, innovative,
      fully automated relapse-prevention programs are highly needed. OBJECTIVE: In this
      study an online, automated relapse-prevention program based on acceptance and
      commitment therapy (ACT)-both as a website and as a mobile app-was developed and
      evaluated. At each step of the development, end users (ie, chronic pain patients)
      were consulted in order to fully address their needs. METHODS: In a step-by-step
      process, a contextual inquiry, requirement specification, and design were
      executed with chronic pain patients by conducting, respectively, a focus group
      (n=10), interviews with rapid prototyping (n=28), and a user- and expert-based
      usability evaluation (n=14). Furthermore, a pilot evaluation was conducted with
      14 chronic pain or fatigue patients who had received the online relapse
      prevention program following a multidisciplinary ACT treatment. They were
      interviewed about their usage and the usefulness of the program in supporting
      them to maintain changed behaviors and prevent relapses in avoidance and pain
      control behaviors. RESULTS: The three stages provided information about the
      expected needs of end users, comments about the usefulness of the proposed
      features, and feedback about the design and usability of the program. This
      resulted in a fully operational, online relapse-prevention program. Results from
      the pilot evaluation showed that 9 patients used the online program after
      treatment, 5 of whom indicated that the program supported them after treatment.
      Of all the patients, 4 of them indicated that the program did not support them
      because they wanted more social interaction with other users. CONCLUSIONS: This
      study showed that an innovative, automated, online program that is user friendly
      can be developed by involving the end users in each step. The program was
      evaluated positively by some participants. The evaluation showed that the online
      relapse-prevention program has the potential to support chronic pain patients in
      maintaining their changed behaviors and preventing relapses in avoidance and pain
      control behaviors. TRIAL REGISTRATION: Nederlands Trial Register (NTR) Number:
      NTR4177; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4177 (Archived
      by WebCite at http://www.webcitation.org/6Ur6EFD1D).

PMID- 27025551
TI  - Prostatic artery embolization: radiation exposure to patients and staff.
AB  - The aim of this study was to evaluate the radiation doses to patients and staff
      received from the first cases of prostatic artery embolization (PAE) conducted in
      a public hospital in Recife, Brazil. Five PAE procedures for 5 men diagnosed with
      benign prostatic hyperplasia were investigated. In order to characterize patient
      exposure, dosimetric quantities, such as the air kerma-area product (P KA), the
      cumulative air kerma at the interventional reference point (Ka,r), the number of
      images, etc, were registered. To evaluate the possibility for deterministic
      effects, the peak skin dose (PSD) was measured using radiochromic films. For
      evaluation of personal dose equivalent and effective dose to the medical staff,
      thermoluminescent dosemeters (TLD-100) were used. The effective dose was
      estimated using the double dosimetry alghoritm of von Boetticher. The results
      showed that the mean patient's PSD per procedure was 2674.2 mGy. With regard to
      the medical staff, the mean, minimum and maximum effective doses estimated per
      procedure were: 18 MUSv, 12 MUSv and 21 MUSv respectively. High personal
      equivalent doses were found for the feet, hands and lens of the eye, due to the
      use of multiple left anterior oblique projections and the improper use of the
      suspended lead screen and the lead curtain during procedures. 

PMID- 27025552
TI  - A lasting effect of postnatal sevoflurane anesthesia on the composition of NMDA
      receptor subunits in rat prefrontal cortex.
AB  - Sevoflurane is widely used in pediatric anesthesia and studies have shown that it
      is capable of inducing neurodegeneration and subsequent cognitive disorders in
      the developing brain. However, the evidence that anesthetics are toxic to the
      human brain is insufficient. N-Methyl-d-aspartate (NMDA) receptors, critical for
      learning and memory, display expression changes with age and can be modulated by
      inhalation anesthetics. Generally, NMDA receptor (NR) type 1 is expressed at
      birth, peaks around the third postnatal week, and then declines slightly to adult
      levels. NR2Bs slowly decrease and NR2As gradually increase during postnatal
      development. These developmental switches of NMDA receptor subunits composition
      mark the transition from immature to adult neural processing and allow for the
      final maturation of associative learning abilities. In this study, we aimed to
      evaluate the effect of repeated sevoflurane anesthesia on NMDA receptor subunits
      composition in the developing rat brain and related behavioral disorders. Six-day
      old male Sprague Dawley rats were randomly allocated into either a control group
      (group con) or a sevoflurane group (group sevo). Group sevo inhaled 2.1%
      sevoflurane carried by 70% oxygen for 2h each day from postnatal day (PND) 6 to
      PND 8. The same procedure, without applying the sevoflurane, was executed in
      group con. The membrane protein expression of NR1, NR2A and NR2B in the
      prefrontal cortex (PFC) and hippocampus was assessed at the end of the three days
      of anesthesia and at PND 21. An open field test was carried out to assess
      spontaneous locomotion on PNDs 21, 28 and 35. Y maze performance was used to
      assess attention and working memory on PND 28. Sevoflurane induced upregulation
      of NR1 and NR2B in the PFC at the end of anesthesia. On PND 21, NR1 and NR2B
      receptors were significantly increased whereas NR2A receptors were significantly
      decreased in the PFC in group sevo. Sevoflurane-treated rats showed hyper
      locomotion and impairment of working memory in the behavior tests. These results
      indicate that repeated sevoflurane anesthesia at early stage of life can induce a
      long lasting effect of interfering with NMDA receptor subunits composition in rat
      PFC. These changes may contribute to the effects of sevoflurane on neuronal
      development and subsequent neurobehavioral disorders.

PMID- 27025553
TI  - IFN-tau inhibits S. aureus-induced inflammation by suppressing the activation of
      NF-kappaB and MAPKs in RAW 264.7 cells and mice with pneumonia.
AB  - Staphylococcus aureus (S. aureus), a significant cause of pneumonia, leads to
      severe inflammation. Few effective treatments or drugs have been reported for S.
      aureus infection. Interferon tau (IFN-tau) is a type I interferon with low
      cellular toxicity even at high doses. Previous studies have reported that IFN-tau
      could significantly mitigate tissue inflammation; however, IFN-tau treatment in
      S. aureus-induced pneumonia has not been well reported. Thus, the aim of this
      study was to identify the anti-inflammatory mechanism of IFN-tau in S. aureus
      induced pneumonia in mice. A S. aureus-induced pneumonia model and RAW 264.7
      cells were used in this research. The histopathological as well as lung wet to
      dry ratio (W/D) and myeloperoxidase (MPO) activity results showed that IFN-tau
      could protect the lung from S. aureus damage. In addition, ELISA and qPCR
      revealed that IFN-tau treatment led to a decreased expression of pro-inflammatory
      cytokines (TNF-alpha, IL-1beta, and IL-6) in both the cells and mouse model, but
      IL-10 was increased. TLR2, which is involved in the response during S. aureus
      infection, was also down-regulated by IFN-tau treatment and directly affected NF
      kappaB and MAPK pathway activation. Then, we examined the phosphorylation of
      IkappaBalpha, NF-kappaB p65 and MAPKs by western blotting, and the results
      displayed that the phosphorylation of IkappaBalpha, NF-kappaB p65 and MAPKs was
      inhibited upon IFN-tau treatment in both the cells and mouse model. These
      findings indicate that IFN-tau has anti-inflammatory properties in vitro and in
      vivo through the inhibition of NF-kappaB and MAPK activation, suggesting that IFN
      tau may have potential as a therapeutic agent against S. aureus-induced
      inflammatory diseases. 

PMID- 27025554
TI  - Dental consultations in UK general practice and antibiotic prescribing rates: a
      retrospective cohort study.
AB  - BACKGROUND: The frequency of consulting for dental problems in general medical
      practice, and antibiotic prescribing associated with these consultations, is
      poorly described. AIM: To describe consultation rates and antibiotic use for
      dental problems in UK general medical practice, and explore factors associated
      with antibiotic prescribing for dental conditions. DESIGN AND SETTING: A
      retrospective cohort study using Clinical Practice Research Datalink, a database
      of general practice patient records in the UK. METHOD: All dental consultations
      between 2004 and 2013 were identified. The main outcome was the prescription of
      an antibiotic during a dental consultation. Multilevel logistic regression was
      conducted to examine factors associated with antibiotic prescription. RESULTS: In
      all, 288 169 dental consultations were included in the cohort. The average rate
      of dental consultations was 6.06 consultations per 1000 patient-years. Rates of
      dental consultation decreased from 6.84 consultations per 1000 patient-years in
      2008, to 4.23 consultations per 1000 patient-years in 2013. Consultation rates
      were higher among females than males and highest in patients aged 20-29 years. An
      antibiotic was prescribed in 57.1% of consultations. Significant predictors
      (P<0.001) of antibiotic prescribing included: patient middle age, male sex, and
      previous consultations for tooth-related problems. Antibiotics were more likely
      to be prescribed during consultations in December (odds ratio [OR] 1.18, 95%
      confidence interval [CI] = 1.13 to 1.24, P<0.001, reference month: June) and on a
      Monday (OR 1.10, 95% CI = 1.07 to 1.13, P<0.001) or a Friday (OR 1.15, 95% CI =
      1.12 to 1.18, P<0.001, reference day: Wednesday). CONCLUSION: Consultation rates
      for dental problems in UK general practice are relatively low but more than half
      result in the prescription of an antibiotic. This raises concerns about patient
      morbidity and contributions to antimicrobial resistance.

PMID- 27025555
TI  - Accuracy of monitors used for blood pressure checks in English retail pharmacies:
      a cross-sectional observational study.
AB  - BACKGROUND: Free blood pressure (BP) checks offered by community pharmacies
      provide a potentially useful opportunity to diagnose and/or manage hypertension,
      but the accuracy of the sphygmomanometers in use is currently unknown. AIM: To
      assess the accuracy of validated automatic BP monitors used for BP checks in a UK
      retail pharmacy chain. DESIGN AND SETTING: Cross-sectional, observational study
      in 52 pharmacies from one chain in a range of locations (inner city, suburban,
      and rural) in central England. METHOD: Monitor accuracy was compared with a
      calibrated reference device (Omron PA-350), at 50 mmHg intervals across the range
      0-300 mmHg (static pressure test), with a difference from the reference monitor
      of +/- 3 mmHg at any interval considered a failure. The results were analysed by
      usage rates and length of time in service. RESULTS: Of 61 BP monitors tested,
      eight (13%) monitors failed (that is, were >3 mmHg from reference), all of which
      underestimated BP. Monitor failure rate from the reference monitor of +/- 3 mmHg
      at any testing interval varied by length of time in use (2/38, 5% <18 months;
      4/14, 29% >18 months, P = 0.038) and to some extent, but non-significantly, by
      usage rates (4/22, 18% in monitors used more than once daily; 2/33, 6% in those
      used less frequently, P = 0.204). CONCLUSION: BP monitors within a pharmacy
      setting fail at similar rates to those in general practice. Annual calibration
      checks for blood pressure monitors are needed, even for new monitors, as these
      data indicate declining performance from 18 months onwards.

PMID- 27025556
TI  - Low hepatitis B testing among migrants: a cross-sectional study in a UK city.
AB  - BACKGROUND: In 2012, hepatitis B virus (HBV) testing of people born in a country
      with a prevalence of >=2% was recommended in the UK. Implementation of this
      recommendation requires an understanding of prior HBV testing practice and
      coverage, for which there are limited data. AIM: To estimate the proportion of
      migrants tested for HBV and explore GP testing practices and barriers to testing.
      DESIGN AND SETTING: A cross-sectional study of (a) migrants for whom testing was
      recommended under English national guidance, living in Bristol, and registered
      with a GP in 2006-2013, and (b) GPs practising in Bristol. METHOD: NHS patient
      demographic data and HBV laboratory surveillance data were linked. A person was
      defined as 'HBV-tested' if a laboratory result was available. An online GP survey
      was undertaken, using a structured questionnaire. RESULTS: Among 82 561 migrants
      for whom HBV testing was recommended, 9627 (12%) were 'HBV-tested'. The HBV
      testing coverage was: Eastern Africa 20%; Western Africa 15%; South Eastern Asia
      9%; Eastern Asia 5%. Of 19 GPs, the majority did not use guidelines to inform HBV
      testing in migrants and did not believe routine testing of migrants was
      indicated; 12/17 GPs stated that workload and lack of human, and financial
      resources were the most significant barriers to increased testing. CONCLUSION:
      The majority of migrants to a multicultural UK city from medium-/high-prevalence
      regions have no evidence of HBV testing. Much greater support for primary care in
      the UK and increased GP awareness of national guidance are required to achieve
      adherence to current testing guidance.

PMID- 27025557
TI  - Electrocardiogram interpretation and arrhythmia management: a primary and
      secondary care survey.
AB  - BACKGROUND: There is increasing desire among service commissioners to treat
      arrhythmia in primary care. Accurate interpretation of the electrocardiogram
      (ECG) is fundamental to this. ECG interpretation has previously been shown to
      vary widely but there is little recent data. AIM: To examine the interpretation
      of ECGs in primary and secondary care. DESIGN AND SETTING: A cross-sectional
      survey of participants' interpretation of six ECGs and hypothetical management of
      patients based on those ECGs, at primary care educational events, and a
      cardiology department in Leeds. METHOD: A total of 262 primary care clinicians
      and 20 cardiology clinicians were surveyed via questionnaire. Answers were
      compared with expert electrophysiologist opinion. RESULTS: In primary care,
      abnormal ECGs were interpreted as normal by 23% of responders. ST elevation and
      prolonged QT were incorrectly interpreted as normal by 1% and 22%, respectively.
      In cardiology, abnormal ECGs were interpreted as normal by 3%. CONCLUSION: ECG
      provision and interpretation remains inconsistent in both primary and secondary
      care. Primary care practitioners are less experienced and less confident with ECG
      interpretation than cardiologists, and require support in this area.

PMID- 27025558
TI  - Tumour stage and implementation of standardised cancer patient pathways: a
      comparative cohort study.
AB  - BACKGROUND: Some European countries have introduced standardised cancer patient
      pathways (CPPs), including urgent referrals, with the aim of diagnosing cancer at
      an earlier stage. This is despite a lack of evidence, particularly in patients
      with symptomatic cancer diagnosed via general practice. AIM: To compare tumour
      stages in patients with incident cancer diagnosed via general practice before,
      during, and after CPP implementation in Denmark in 2008-2009. DESIGN AND SETTING:
      A comparative cohort study of data from GPs and registries on patients with
      incident cancer listed with a GP before (n = 1420), during (n = 5272), and after
      (n = 2988) CPP implementation. METHOD: chi(2) test was used to compare stage
      distributions and logistic regression to estimate odds ratios (OR) of having
      local cancer after versus before CPP implementation. RESULTS: Distribution of
      tumour stages did not differ statistically significantly across time (P = 0.494)
      or between CPP use (P = 0.202). For all cancers combined, the OR of having local
      cancer after CPP implementation was 0.88 (95% confidence interval [CI] = 0.73 to
      1.06) compared with before. For CPP-referred patients, the OR of having local
      cancer was 0.77 (95% CI = 0.62 to 0.94) compared with all patients before CPP
      implementation; the corresponding OR for non-CPP-referred patients was 0.96 (95%
      CI = 0.80 to 1.14). CONCLUSION: No clear tendencies were observed confirming
      earlier detection of cancer after rather than before CPP implementation. CPP
      referred patients had lower odds of having local cancer after CPP implementation
      than all patients before CPP implementation; this could be because the GPs refer
      patients who are 'more ill' as urgent referrals.

PMID- 27025559
TI  - Syntheses and Anti-inflammatory Activity of Natural 1,3-Diarylpropenes.
AB  - First syntheses of five natural 1,3-diarylpropenes (cinnamylphenols) 2-4, 7, and
      8 along with synthesis of two other natural 1,3-diarylpropenes 1 and 5 and E
      isomer of mucronulastyrene (6) were achieved by Friedel-Crafts alkylation as a
      key step. Subsequently, their anti-inflammatory effects were also investigated in
      lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The compounds exhibited
      significant inhibition of inflammatory mediated nitric oxide (NO) production with
      no cytotoxicity except compound 8 (dalberatin B) at 10 uM concentration and IC50
      values were found in the range from 4.05 to 16.76 uM. 

PMID- 27025560
TI  - [Traditional doctorate thesis or by a compendium of publications?]

PMID- 27025561
TI  - Trimethylamine-N-oxide switches from stabilizing nature: A mechanistic outlook
      through experimental techniques and molecular dynamics simulation.
AB  - In adaptation biology of the discovery of the intracellular osmolytes, the
      osmolytes are found to play a central role in cellular homeostasis and stress
      response. A number of models using these molecules are now poised to address a
      wide range of problems in biology. Here, a combination of biophysical
      measurements and molecular dynamics (MD) simulation method is used to examine the
      effect of trimethylamine-N-oxide (TMAO) on stem bromelain (BM) structure,
      stability and function. From the analysis of our results, we found that TMAO
      destabilizes BM hydrophobic pockets and active site as a result of concerted
      polar and non-polar interactions which is strongly evidenced by MD simulation
      carried out for 250 ns. This destabilization is enthalpically favourable at
      higher concentrations of TMAO while entropically unfavourable. However, to the
      best of our knowledge, the results constitute first detailed unambiguous proof of
      destabilizing effect of most commonly addressed TMAO on the interactions
      governing stability of BM and present plausible mechanism of protein unfolding by
      TMAO.

PMID- 27025562
TI  - Magnetic phases of spin-1 spin-orbit-coupled Bose gases.
AB  - Phases of matter are characterized by order parameters describing the type and
      degree of order in a system. Here we experimentally explore the magnetic phases
      present in a near-zero temperature spin-1 spin-orbit-coupled atomic Bose gas and
      the quantum phase transitions between these phases. We observe ferromagnetic and
      unpolarized phases, which are stabilized by spin-orbit coupling's explicit
      locking between spin and motion. These phases are separated by a critical curve
      containing both first- and second-order transitions joined at a tricritical
      point. The first-order transition, with observed width as small as h * 4 Hz,
      gives rise to long-lived metastable states. These measurements are all in
      agreement with theory.

PMID- 27025563
TI  - Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and
      molecular docking study of pyrazoline derivatives.
AB  - Design, synthesis and pharmacological activities of a group of 1,3,5
      trisubstituted pyrazolines were reported. The chemical structures of the
      synthesized compounds have been assigned on the basis of IR, MS, (1)H NMR, and
      (13)C NMR spectral analyses. The synthesized 1,3,5-trisubstituted pyrazoline
      derivatives were evaluated in vivo for anti-inflammatory, analgesic activities
      and in vitro for COX-1/2 inhibition assay. Among the tested compounds,
      derivatives 4h, 6e, 7a, 7e, and 9 showed more potent anti-inflammatory and
      analgesic activities than the reference drug celecoxib. On the basis of their
      higher activities in the in vivo studies compared with celecoxib, the five
      compounds 4h, 6e, 7a, 7e and 9 were selected to test their inhibitory activities
      against ovine COX-1/2 using an in vitro cyclooxygenase inhibition assay. Docking
      study of compounds 7a, 7e and 9 into the COX-2 binding site revealed a similar
      binding mode to SC-558, a selective COX-2 inhibitor. 

PMID- 27025564
TI  - Acridin-3,6-dialkyldithiourea hydrochlorides as new photosensitizers for
      photodynamic therapy of mouse leukemia cells.
AB  - Acridin-3,6-dialkyldithiourea hydrochlorides (AcrDTUs) have been evaluated as a
      new group of photosensitizers (PSs) for photodynamic antitumor therapy (PDT).
      Mouse leukemia cells L1210 were used for testing of AcrDTUs as the new PSs. The
      irradiation (UV-A light (365 nm), 1.05 J/cm(2)) increased cytotoxicity of all
      derivatives against L1210 cells more than ten times. The highest
      photocytotoxicity was found for propyl-AcrDTU with IC50=0.48+/-0.03 MUM after 48
      h incubation. A generation of the superoxide radical anion upon UV-A irradiation
      of propyl-AcrDTU was confirmed by in situ photochemical EPR experiments. To
      explain a mechanism of photocytotoxic action of AcrDTUs, an intracellular
      distribution of propyl-AcrDTU has been studied. It was found that AcrDTU in non
      irradiated cells was not present in their nucleus but in the lysosomes and partly
      in the mitochondria, and sequestration of propyl-AcrDTU was dependent on pH in
      lysosomes. After irradiation, the cell death was induced by oxidative damage of
      lysosomal and mitochondrial membranes. Concerning the cell cycle, flow cytometry
      after PDT with propyl-AcrDTU showed a significant increase of the cells in the
      subG0 phase. Observed signs of necrosis, apoptosis, and autophagy indicate that
      PDT/AcrDTU leads to multiple cell death types (caspase independent apoptosis,
      necrosis, and autophagy).

PMID- 27025565
TI  - Prediction and verification of novel peptide targets of protein tyrosine
      phosphatase 1B.
AB  - Phosphotyrosine peptides are useful starting points for inhibitor design and for
      the search for protein tyrosine phosphatase (PTP) phosphoprotein substrates. To
      identify novel phosphopeptide substrates of PTP1B, we developed a computational
      prediction protocol based on a virtual library of protein sequences with known
      phosphotyrosine sites. To these we applied sequence-based methods, biologically
      meaningful filters and molecular docking. Five peptides were selected for
      biochemical testing of their potential as PTP1B substrates. All five peptides
      were equally good substrates for PTP1B compared to a known peptide substrate
      whereas appropriate control peptides were not recognized, showing that our
      protocol can be used to identify novel peptide substrates of PTP1B.

PMID- 27025566
TI  - Human pseudoarthrosis tissue contains cells with osteogenic potential.
AB  - INTRODUCTION: Nonunion is a challenging problem that may occur after certain bone
      fractures. The treatment of nonunion is closely related to its type. To develop
      an effective treatment strategy for each type of nonunion, biological analysis of
      nonunion tissue is essential. Pseudoarthrosis is a distinct pathologic entity of
      nonunion. To understand the pathology of pseudoarthrosis, we investigated the
      cellular properties of pseudoarthrosis tissue-derived cells (PCs) in vitro.
      PATIENTS AND METHODS: PCs were isolated from four patients with pseudoarthrosis
      and cultured. Cells were evaluated for cell-surface protein expression by using
      flow cytometry. Osteogenic differentiation capacity was assessed by using
      Alizarin Red S staining, alkaline phosphatase (ALP) activity assay, and reverse
      transcription polymerase chain reaction (RT-PCR) after osteogenic induction.
      Chondrogenic differentiation capacity was assessed via Safranin O staining and RT
      PCR after chondrogenic induction. RESULTS: PCs were consistently positive for the
      mesenchymal stem cell-related markers CD29, CD44, CD105, and CD166, but were
      negative for the haematopoietic-lineage markers CD31, CD34, CD45, and CD133.
      Alizarin Red S staining revealed that PCs formed a mineralised matrix that was
      rich in calcium deposits after osteogenic induction. ALP activity under
      osteogenic conditions was significantly higher than that under control
      conditions. Gene expression of ALP, Runx2, osterix, osteocalcin, and bone
      sialoprotein was observed in PCs cultured under osteogenic conditions. Induced
      pellets were negatively stained by Safranin O staining. Gene expression of
      aggrecan, collagen II, collagen X, SOX5, and SOX9 was not observed. CONCLUSION:
      We have shown for the first time the properties of cells in patients with
      pseudoarthrosis. Our results indicated that osteogenic cells existed in the
      pseudoarthrosis tissue. This study might provide insights into understanding the
      pathology of pseudoarthrosis and improving the treatment for pseudoarthrosis.

PMID- 27025567
TI  - Alcohol consumption decreases lactate clearance in acutely injured patients.
AB  - INTRODUCTION: Alcohol, a common risk factor for injury, has direct toxic effects
      on the liver. The use of lactate clearance has been well described as an
      indicator of the adequacy of resuscitation in injured patients. We investigated
      whether acutely injured patients with positive blood alcohol content (+BAC) had
      less lactate clearance than sober patients. METHODS: We conducted a retrospective
      cohort study of acutely injured patients treated at an urban Level 1 trauma
      centre between January 2010 and December 2012. Blood alcohol and venous lactate
      levels were measured on all patients at the time of arrival. Study subjects were
      patients transported directly from the scene of injury, who had an elevated
      lactate concentration on arrival (>=3.0mmol/L) and at least one subsequent
      lactate measurement within 24h after admission. Lactate clearance ([Lactate1
      Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used
      to compare values from sober and intoxicated subjects. Lactate clearance was
      plotted against alcohol levels and stratified by age and Injury Severity Score
      (ISS). RESULTS: Serial lactate concentration measurements were obtained in 3910
      patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6
      [SD 14.7] vs 41.0 [SD 19.9] years [p=0.0001]), were more often male (83.4% vs
      75.9% [p=0.0001]), had more minor injuries (ISS<9) (33.8% vs 27.1% [p=0.0001]),
      had a lower in-hospital mortality rate (1.4% vs 3.9% [p=0.0001]), but also had
      lower average lactate clearance (37.8% vs 47.6% [p=0.0001]). The lactate
      clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with
      +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC
      irrespective of age and ISS. CONCLUSIONS: In a large group of acutely injured
      patients, a dose-dependent decrease in lactate clearance was seen in those with
      elevated BAC. This relationship will cause a falsely elevated lactate reading or
      prolong lactate clearance and should be taken into account when evaluating
      patients with +BAC.

PMID- 27025568
TI  - Survival of the Grittiest? Consultant Surgeons Are Significantly Grittier Than
      Their Junior Trainees.
AB  - OBJECTIVE: "Grit" can be defined as the passion and perseverance for long-term
      goals, and it can be measured by a validated scale. It has been associated with
      success in diverse fields such as basic military training and spelling tests.
      Surgical training is arduous with large number of trainees reporting burnout, and
      it could be expected that grit is a fundamental requirement to complete training.
      This study aimed to examine the relationship of grit in surgical training,
      whether grit varies by grade of surgeon, and the association of grit with
      burnout. DESIGN: This was a prospective survey-based study, using the validated
      tools Short Grit Scale and Oldenburg Burnout Inventory. SETTING: UK-based ear,
      nose, and throat doctors based in secondary care were invited to participate.
      PARTICIPANTS: Ear, nose, and throat surgeons were used as the sample population,
      with subgroups of core trainees (core surgical trainees), specialist registrars
      (higher surgical training), and consultants. RESULTS: A total of 102 participants
      completed the study (33 core surgical trainees, 49 mid-career trainees in higher
      surgical training, and 22 consultants). Consultants were significantly grittier
      than trainees (p < 0.05). Grit had a significant inverse relationship with
      burnout (r = -0.54, p < 0.05). There was a nonsignificant trend of reduced
      burnout in consultants. Age and sex were not associated with grit or burnout.
      CONCLUSIONS: These findings reinforce the concept that grit is fundamentally
      important to completion of surgical training. In addition, grittier individuals
      are more likely to resist burnout than their less gritty counterparts. These
      findings carry implications for retention and recruitment of trainee surgeons,
      and further study is required to investigate whether surgical training influences
      grit levels or selects out the grittiest trainees to survive to completion.

PMID- 27025569
TI  - Palliative balloon dilation of pulmonic stenosis in a dog with tetralogy of
      Fallot.
AB  - A 6-month-old Beagle with tetralogy of Fallot underwent balloon valvuloplasty of
      the pulmonary valve. Balloon valvuloplasty was successful and resulted in
      palliation of clinical signs and an improved quality of life for approximately 9
      months. After 9 months, the dog became symptomatic and a modified Blalock-Taussig
      shunt procedure was successfully performed. Based on this report, balloon
      valvuloplasty in dogs with tetralogy of Fallot appears to be a feasible technique
      that may result in improvement of clinical signs. In addition, it may allow for
      the delay of the more invasive surgical palliation and provide time for weight
      gain and development of the pulmonary vascular bed for greater ease of surgical
      shunt creation. 

PMID- 27025570
TI  - Development of experimental resin modified glass ionomer cements (RMGICs) with
      reduced water uptake and dimensional change.
AB  - OBJECTIVE: To investigate water uptake, desorption, diffusion coefficient,
      solubility and dimensional changes of four experimental RMGICs in deionized water
      (DW) and artificial saliva (AS), and compare with two commercial RMGICs and
      control home liquids based on the two commercial materials used. METHODS: Two
      commercial RMGICs, RelyX Luting (RX, 3M ESPE) and Fuji Plus (FP, GC), two control
      home liquids and four new liquid compositions (F1, F2, R1, R2) comprising
      different percentages of the monomer THFM (tetrahydrofurfuryl-methacrylate) with
      the original monomer HEMA (2-hydroxyethyl-methacrylate) were used in this study.
      Home and experimental liquids were mixed with the corresponding commercial
      powder. Disk-shaped specimens (16mm diameter 1mm thickness) were immersed in
      DW/AS at 37 degrees C (n=6) and weighed at regular time intervals. Percentage
      weight change with time was recorded. At 24 weeks, disks were desorbed in an oven
      at 37 degrees C to minimum weight. RESULTS: All new compositions showed lower
      water uptake and dimensional (volume) changes than the commercial products in
      both DW and AS. On desorption, FP showed higher weight loss compared to materials
      in the same group in both solutions (p<0.0001), with the exception of F2 in DW
      (p=0.283). RX had higher weight loss compared to R1 and R2 in DW and AS
      (p<0.0001). Fickian diffusion was confirmed for all materials immersed in DW and
      AS. SIGNIFICANCE: The experimental compositions in this study have shown
      promising results when tested in both DW and AS with lower water uptakes and
      volume changes than commercial materials. This may lead to wider applications
      than current commercial materials.

PMID- 27025571
TI  - Sleeping Beauty transposase structure allows rational design of hyperactive
      variants for genetic engineering.
AB  - Sleeping Beauty (SB) is a prominent Tc1/mariner superfamily DNA transposon that
      provides a popular genome engineering tool in a broad range of organisms. It is
      mobilized by a transposase enzyme that catalyses DNA cleavage and integration at
      short specific sequences at the transposon ends. To facilitate SB's applications,
      here we determine the crystal structure of the transposase catalytic domain and
      use it to model the SB transposase/transposon end/target DNA complex. Together
      with biochemical and cell-based transposition assays, our structure reveals
      mechanistic insights into SB transposition and rationalizes previous hyperactive
      transposase mutations. Moreover, our data enables us to design two additional
      hyperactive transposase variants. Our work provides a useful resource and proof
      of-concept for structure-based engineering of tailored SB transposases. 

PMID- 27025572
TI  - Identification of essential and non-essential genes in Ambystoma tigrinum virus.
AB  - Members of the genus Ranavirus (family Iridoviridae) are large double-stranded
      (ds) DNA viruses that are found world-wide infecting fish, amphibian and reptile
      ectothermic hosts. Ranavirus genomes range from 105 to 155kbp in length and they
      are predicted to encode around 90-125 genes. Currently, our knowledge of the
      function of ~50% of these genes is known or inferred based on homology to
      orthologous genes characterized in other systems; however, the function of the
      remaining open reading frames (ORFS) is unknown. Therefore, in order to begin to
      uncover the function of unknown ORFs in ranaviruses we developed a standardized
      approach to generate a recombination cassette for any ORF in Ambystoma tigrinum
      virus (ATV). Our standardized approach quickly and efficiently assembles
      recombination cassettes and recombinant ATV. We have used this approach to
      identify two essential, one semi-essential and two non-essential genes in ATV.

PMID- 27025574
TI  - Breaking Through Dangerous Silence to Tap an Organization's Richest Source of
      Information: Its Own Staff.

PMID- 27025573
TI  - Evaluation of oral Lanzhou lamb rotavirus vaccine via passive transfusion with
      CD4(+)/CD8(+) T lymphocytes.
AB  - Lanzhou Lamb derived Rotavirus (RV) Vaccine (namely LLR) for children is only
      used in China. Since there were no reports on evaluation of LLR, even the data of
      phase IV clinical trial, we proceed the evaluation of LLR through focusing on T
      cell to investigate whether LLR could induce the potential function involving in
      protection as a vaccine. Four groups of nude mice were transfused with
      CD4(+)/CD8(+) T-cells isolated from LLR-immunized (primed) and LLR-unimmunized
      (naive) mice via intraperitonea (i.p.) respectively. Consequently, the adoption
      mice were challenged with mice-origin wild rotavirus EDIM (Epizootic Diarrhea of
      Infant Mice) by intragastric administration. Series of fecal/serum samples were
      collected and viral shedding, then serum IgA/IgG and secreted IgA were assayed.
      Compared to the mice transfused with T lymphocytes from naive mice, the nude mice
      transfused with CD4(+) T lymphocytes from primed mice induce fecal and serum IgA
      increasing more rapidly, and have a shorter duration of virus shedding too.
      Whereas, no significant difference in virus clearance was found between the mice
      transfused with CD8(+) T lymphocytes isolated from primed and naive mice.
      Therefore, we cleared the distinct roles of transfused CD4(+)/CD8(+) T
      lymphocytes for rotavirus clearance in nude mice, that the viral clearance
      conducted by CD4(+) T lymphocytes. Meanwhile, it has ability to help induction of
      LLR specific immunogenicity. Comparing with the transfusion of cell from primed
      and naive mice, LLR can induce CD4(+) T lymphocytes memory which is a potential
      index to reflect the immunogenicity and protection, while CD8(+) T lymphocytes
      remove rotavirus by CTL with little memory ability.

PMID- 27025575
TI  - Using Coworker Observations to Promote Accountability for Disrespectful and
      Unsafe Behaviors by Physicians and Advanced Practice Professionals.
AB  - BACKGROUND: Health care team members are well positioned to observe disrespectful
      and unsafe conduct-behaviors known to undermine team function. Based on
      experience in sharing patient complaints with physicians who subsequently
      achieved decreased complaints and malpractice risk, Vanderbilt University Medical
      Center developed and assessed the feasibility of the Co-Worker Observation
      Reporting System(SM) (CORS (SM)) for addressing coworkers' reported concerns.
      METHODS: VUMC leaders used a "Project Bundle" readiness assessment, which
      entailed identification and development of key people, organizational supports,
      and systems. Methods involved gaining leadership buy-in, recruiting and training
      key individuals, aligning the project with organizational values and policies,
      promoting reporting, monitoring reports, and employing a tiered intervention
      process to address reported coworker concerns. RESULTS: Peer messengers shared
      coworker reports with the physicians and advanced practice professionals
      associated with at least one report 84% of the time. Since CORS inception, 3% of
      the medical staff was associated with a pattern of CORS reports, and 71% of
      recipients of pattern-related interventions were not named in any subsequent
      reports in a one-year follow-up period. CONCLUSIONS: Systematic monitoring of
      documented co-worker observations about unprofessional conduct and sharing that
      information with involved professionals are feasible. Feasibility requires
      organizationwide implementation; co-workers willing and able to share respectful,
      nonjudgmental, timely feedback designed initially to encourage self-reflection;
      and leadership committed to be more directive if needed. Follow-up surveillance
      indicates that the majority of professionals "self-regulate" after receiving CORS
      data.

PMID- 27025576
TI  - Competencies for Patient Safety and Quality Improvement: A Synthesis of
      Recommendations in Influential Position Papers.
AB  - BACKGROUND: There is limited conformity among patient safety and quality
      improvement (QI) competencies of the knowledge, skills, and attitudes (KSA), by
      stage of skill acquisition, essential for all health professionals. A study was
      conducted to identify, categorize, critically appraise, and discuss implications
      of competency recommendations published in influential position papers. METHODS:
      A literature search was conducted of competency recommendations in position
      papers published by national and international professional associations, expert
      panels, consortia, centers and institutes, and convened committees, in the domain
      of patient safety and QI. To be included in the analysis, the competency had to
      be recommended in at least 20% (rounded) of the position papers. Qualitative
      content analysis was used to identify themes among the published competencies for
      the skill acquisition levels of competent and expert, using Dreyfus's
      definitions. RESULTS: On the basis of the 22 papers that met the inclusion
      criteria, 17 themes were identified among the 59 competencies for the skill level
      competent. Among the 23 competencies for the skill level expert, 13 themes were
      identfied. Competencies within the theme "Evidence-Based Practice" were most
      frequently recommended across both skill levels. The themes "Interdisciplinary
      Teamwork and Collaboration" and "Evidence-Based Practice" were the themes
      identified among the greatest number of position papers for the skill level
      competent and expert, respectively. CONCLUSIONS: The identified themes for
      competencies in patient safety and QI have implications for curriculum
      development and assessment of competence in education and practice. The findings
      in this study demonstrate a need to discourage publication of recommendations of
      yet more competencies and to instead encourage development of an international
      consensus on the essential KSA for patient safety and QI across all health
      professions and all levels of skill acquisition.

PMID- 27025577
TI  - Engaging Frontline Leaders and Staff in Real-Time Improvement.
AB  - BACKGROUND: The relationship of staff satisfaction and engagement to
      organizational success, along with the integral influence of frontline managers
      on this dimension, is well established in health care and other industries. To
      specifically address staff engagement, Virginia Mason Medical Center, an
      integrated, single-hospital health system, developed an approach that involved
      leaders, through the daily use of standard work for leaders, as well as staff,
      through a Lean-inspired staff idea system. METHODS: Kaizen Promotion Office (KPO)
      staff members established three guiding principles: (1) Staff engagement begins
      with leader engagement; (2) Integrate daily improve- ment (kaizen) as a habitual
      way of life not as an add-on; and (3) Create an environment in which staff feel
      psycho- logically safe and valued. Two design elements--Standard Work for Leaders
      (SWL) and Everyday Lean Ideas (ELIs) were implemented. RESULTS: For the emergency
      department (ED), an early adopter of the staff engagement work, the challenge was
      to apply the guiding principles to improve staff engagement while improving
      quality and patient and staff satisfaction, even as patient volumes were
      increasing. Daily huddles for the KPO staff members and weekly leader rounds are
      used to elicit staff ideas and foster ELIs in real time. Overall progress to date
      has been tracked in terms of staff satisfaction surveys, voluntary staff
      turnover, adoption of SWL, and testing and implementation of staff ideas. For
      example, voluntary turnover of ED staff decreased from 14.6% in 2011 to 7.5% in
      2012, and 2.0% in 2013. Organizationwide, at least 800 staff ideas are in motion
      at any given time, with finished ones posted in an idea supermarket website.
      CONCLUSION: A leadership and staff engagement approach that focuses on SWL and on
      capturing staff ideas for daily problem solving and improvement can contribute to
      organization success and improve the quality of health care delivery.

PMID- 27025578
TI  - Rural Implications of Expanded Birth Volume Threshold for Reporting Perinatal
      Care Measures.
AB  - BACKGROUND: In 2016 the minimum annual birth volume threshold for required
      reporting of the Joint Commission Perinatal Care measures by accredited hospitals
      decreased from 1,100 to 300 births. METHODS: Publicly available Joint Commission
      Quality Check data from April 2014 to March 2015 for three Perinatal Care
      measures were linked to Medicare Provider of Services and American Hospital
      Association Annual Survey data. For each measure, hospital-level reporting and
      performance among accredited hospitals providing obstetric care were compared
      using Fisher's exact tests. RESULTS: Sixty-seven percent of the 2,396 accredited
      hospitals with obstetric services reported at least one eligible patient for two
      of the four reported Perinatal Care measures: Elective delivery and exclusive
      breast milk feeding. Fewer hospitals (35.0%) had data on the antenatal steroids
      measure; many hospitals may not have any eligible patients for this measure.
      Hospitals with higher birth volume, those in urban counties, and those with
      private, nonprofit ownership or system affiliation were more likely to report the
      perinatal measures (p < 0.001). Across states, reporting rates varied
      considerably. By hospital volume, performance varied more on the antenatal
      steroids measure (78.0% to 91.5%) than on the breast milk feeding measure (48.4%
      to 49.5%) and the elective delivery measure (2.5% to 3.0%). CONCLUSIONS:
      Expansion of the minimum birth volume threshold nearly doubles the number of
      accredited hospitals required to report the Perinatal Care measures to The Joint
      Commission. However, 485 accredited hospitals with obstetric services that are
      either critical access hospitals or have fewer than 300 births annually are still
      exempt from reporting. Although many rural hospitals remain exempt from reporting
      requirements, the measures offer an opportunity for both rural and urban
      hospitals to assess and improve care.

PMID- 27025579
TI  - Ambulatory Medication Reconciliation: Using a Collaborative Approach to Process
      Improvement at an Academic Medical Center.
AB  - BACKGROUND: Incomplete medication reconciliation has been identified as a source
      of adverse drug events and a threat to patient safety. How best to measure and
      improve rates of medication reconciliation in ambulatory care remains unknown.
      METHODS: An institutional collaborative improvement effort to develop and
      implement medication reconciliation processes was designed and facilitated across
      all 148 Brigham and Women's Hospital (Boston) ambulatory specialty practices: 63
      underwent a more rigorous approach, a modified approach was undertaken in another
      71 specialty practices, and a less intensive approach took place in the 14
      primary care practices. The level of intervention varied on the basis of
      preexisting improvement infrastructure and practice prescription rates. Two
      electronically measured metrics were created to evaluate ambulatory visits to a
      provider in which there was a medication change: (1) Measure 1: the percentage of
      active medications prescribed by that provider that were reconciled; and (2)
      Measure 2: how often all the medications prescribed by that provider were
      reconciled. After the collaborative was completed, performance data were
      routinely shared with frontline staff and hospital leadership, and medication
      reconciliation rates became part of an institutional financial incentive program.
      RESULTS: For Measure 1, specialty practices improved from 71% to 90% (September
      2012-August 2014; 24-month period). Primary care practice performance improved
      from 62% to 91% (December 2012-August 2014; 20-month period). For Measure 2,
      overall performance across all ambulatory practices increased from 81% to 90%
      during the first 12 months of the financial incentive program (October 2013-
      September 2014). CONCLUSION: A collaborative model of process improvement paired
      with financial incentives can successfully increase rates of ambulatory
      medication reconciliation.

PMID- 27025581
TI  - Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical
      Characteristics and Novel and Recurrent Mutations in 132 Patients.
AB  - Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group
      of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis
      (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A
      4th subtype has also been proposed: pleomorphic ichthyosis (PI), characterized by
      marked skin changes at birth and subsequently mild symptoms. In nationwide
      screenings of suspected cases of ARCI in Denmark and Sweden, we identified 132
      patients (age range 0.1-86 years) classified as HI (n = 7), LI (n = 70), CIE (n =
      17) and PI (n = 38). At birth, a collodion membrane or similar severe
      hyperkeratosis was reported in almost all patients with HI and LI, and in nearly
      half of patients with CIE and PI. Persistent ectropion was more common in HI
      (85%) and LI (57%), than in CIE (35%) and PI (5%). Anhidrosis was a frequent
      problem in all 4 groups (58-100%). A scoring (0-4) of ichthyosis/ery-thema past
      infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI
      (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found
      in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n =
      8), ALOXE3 (n = 9), SLC27A4 (n = 5), CYP4F22 (n = 3), PNPLA1 (n = 1) and ABHD5 (n
      = 1). In conclusion, by performing a deep phenotyping and gene screening, ARCI
      can be definitely diagnosed in 85% of cases in Scandinavia, with a prevalence of
      1:100,000 and > 8 different aetiologies.

PMID- 27025582
TI  - Folic acid-targeted iron oxide nanoparticles as contrast agents for magnetic
      resonance imaging of human ovarian cancer.
AB  - BACKGROUND: Improved methods for the early and specific detection of ovarian
      cancer are needed. METHODS: In this experimental study, we used folic acid (FA)
      targeted iron oxide (Fe3O4) nanoparticles (NPs) as a T2-negative contrast agent
      for magnetic resonance (MR) imaging to accurately detect ovarian cancer tissues
      in an intraperitoneal xenograft tumor model. Human serous ovarian cell line (Skov
      3), with overexpressed FA receptors, was chosen as the targeted tumor cell mode.
      For in vivo experiments, the cells were injected intraperitoneally into nude mice
      to produce intraabdominal ovarian cancers. FA-targeted and non-targeted Fe3O4 NPs
      were prepared. RESULTS: FA-targeted Fe3O4 NPs with a mean size of 9.2 +/- 1.7 nm
      have a negligible cytotoxicity to human serous ovarian cell line (Skov-3).
      Importantly, the results of cellular uptake suggested that FA-targeted Fe3O4 NPs
      have a targeting specificity to Skov-3 cells overexpressing FA receptors. FA
      targeted Fe3O4 NPs could be specifically localized by magnetic resonance (MR)
      imaging to the intraperitoneal human ovarian carcinoma tissues, as documented by
      a statistically significant difference (p = 0.002, n = 3) in T2 signal
      intensities of xenograft tumor tissues when injected with FA-targeted and non
      targeted Fe3O4 NPs at 4 h post-injection. CONCLUSION: FA-targeted Fe3O4 NPs
      appear to be promising agents for the detection of human ovarian carcinoma by MR
      imaging, and possibly also for the hyperthermal treatment of the tumors.

PMID- 27025583
TI  - Rethinking the role and impact of health information technology: informatics as
      an interventional discipline.
AB  - Recent advances in the adoption and use of health information technology (HIT)
      have had a dramatic impact on the practice of medicine. In many environments,
      this has led to the ability to achieve new efficiencies and levels of safety. In
      others, the impact has been less positive, and is associated with both: 1)
      workflow and user experience dissatisfaction; and 2) perceptions of missed
      opportunities relative to the use of computational tools to enable data-driven
      and precise clinical decision making. Simultaneously, the "pipeline" through
      which new diagnostic tools and therapeutic agents are being developed and brought
      to the point-of-care or population health is challenged in terms of both cost and
      timeliness. Given the confluence of these trends, it can be argued that now is
      the time to consider new ways in which HIT can be used to deliver health and
      wellness interventions comparable to traditional approaches (e.g., drugs,
      devices, diagnostics, and behavioral modifications). Doing so could serve to
      fulfill the promise of what has been recently promoted as "precision medicine" in
      a rapid and cost-effective manner. However, it will also require the health and
      life sciences community to embrace new modes of using HIT, wherein the use of
      technology becomes a primary intervention as opposed to enabler of more
      conventional approaches, a model that we refer to in this commentary as
      "interventional informatics". Such a paradigm requires attention to critical
      issues, including: 1) the nature of the relationships between HIT vendors and
      healthcare innovators; 2) the formation and function of multidisciplinary teams
      consisting of technologists, informaticians, and clinical or scientific subject
      matter experts; and 3) the optimal design and execution of clinical studies that
      focus on HIT as the intervention of interest. Ultimately, the goal of an
      "interventional informatics" approach can and should be to substantially improve
      human health and wellness through the use of data-driven interventions at the
      point of care of broader population levels. Achieving a vision of "interventional
      informatics" will requires us to re-think how we study HIT tools in order to
      generate the necessary evidence-base that can support and justify their use as a
      primary means of improving the human condition. 

PMID- 27025584
TI  - Serum cholinesterase: a potential assistant biomarker for hand, foot, and mouth
      disease caused by enterovirus 71 infection.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71)
      is a potentially life-threatening infectious disease that commonly occurs in
      children. Diagnosis of HFMD caused by EV71 largely depends on clinical
      manifestations and rare serological biomarkers used to identify children
      suffering from HFMD. Serum cholinesterase (SChE) activity has frequently been
      reported as a potential biomarker for solid central nervous system tumors,
      chronic heart failure, and liver cirrhosis. However, its potential value in the
      diagnosis of neurotropic virus infections, such as HFMD caused by EV71, remains
      to be determined. FINDINGS: In our study, 220 children hospitalized with HFMD
      caused by EV71, 34 inpatients infected with coxsackievirus A16 (CVA16), and 43
      undefined enterovirus-infected HFMD inpatients were recruited at the Anhui
      Provincial Children's Hospital between January 2011 and December 2012. SChE
      activity was measured. The non-parametric Mann-Whitney U test showed that SChE
      activity in children diagnosed with HFMD caused by EV71 was significantly higher
      than in healthy controls (p < 0.001), as well as in children with upper
      respiratory tract infections (p = 0.011), bronchopneumonia (p < 0.001),
      septicemia (p < 0.001), amygdalitis (p < 0.001), and appendicitis (p < 0.001). In
      addition, higher SChE activity was observed in male inpatients with HFMD caused
      by EV71 (47.7 % positivity) compared to female inpatients (26.1 % positivity)
      (chi-square test, p = 0.002). In our study, no significant differences in SChE
      levels were observed among different ages (up to 120 months) (r = -0.112, p >
      0.05). An important finding was that SChE activity declined in the recovery phase
      of HFMD caused by EV71 compared to the acute phase (p < 0.001). CONCLUSIONS:
      Elevated SChE activity was observed in patients with severe HFMD caused by EV71.
      Therefore, SChE might be a potential assistant biomarker for the diagnosis of
      HFMD caused by EV71 in children.

PMID- 27025585
TI  - A diagnostic approach that may help to discriminate inherited thrombocytopenia
      from chronic immune thrombocytopenia in adult patients.
AB  - Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that
      are often confused with immune thrombocytopenia (ITP). The objective of this
      study was to supply clinicobiological elements that allow a distinction to be
      drawn between IT and chronic ITP. We then compared 23 adult patients with IT and
      9 patients with chronic ITP. Our study revealed six discriminating criteria: (i)
      an age of discovery <34 years: positive predictive value (PPV) = 88.2% [63.6;
      98.5], (ii) a family history of thrombocytopenia: PPV = 100.0% [82.4; 100.0],
      (iii) a personal history of bleeding: PPV = 100% [76.8; 100.0], (iv) a mean
      platelet volume >11 fL: PPV = 93.3% [68.1; 99.8], (v) an excess of giant
      platelets on blood smear: 100.0% [76.8; 100.0], and (vi) a percentage >44% of
      platelets with a surface area >4 um(2) in electron microscopy: PPV = 83.3% [58.6;
      96.4]. If at least three of these criteria were combined, it was possible to
      distinguish IT from chronic ITP with 91.3% [72.0; 98.9] sensitivity and PPV =
      100.0% [66.4; 100.0] specificity. The secondary objective of this study was to
      assess the prevalence of potential IT diagnosis in patients with chronic
      thrombocytopenia of uncertain origin. Applying our diagnostic approach to a
      series of 20 cases allowed us to estimate that 40% of them could be suffering
      from IT. Finally, our diagnostic approach may help to correctly distinguish IT
      from chronic ITP, particularly in the context of macrothrombocytopenia. 

PMID- 27025586
TI  - Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic
      Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to
      Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results
      of The Scandinavian Prostate Cancer Group-7.
AB  - BACKGROUND: In high-risk prostate cancer (PCa), no study with observation times
      beyond 10 yr has demonstrated survival improvement after addition of prostatic
      radiotherapy (RAD) to endocrine treatment (ET) alone. OBJECTIVE: To compare
      mortality rates in patients receiving ET alone versus ET + RAD. DESIGN, SETTINGS,
      AND PARTICIPANTS: From 1996 to 2002, 875 Scandinavian patients with high-risk
      (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian
      Prostate Cancer Group-7). After 3 mo with total androgen blockade in all
      patients, all individuals continued lifelong antiandrogen monotherapy. Those
      randomized to ET + RAD started prostate radiotherapy (70Gy) at 3 mo. OUTCOME,
      MEASUREMENTS AND STATISTICAL ANALYSIS: PCa-specific 15-yr mortality represented
      the primary endpoint. Assessment of the combination treatment effect and
      prognostic factors was performed in competing risk analyses and Cox proportional
      hazard models. INTERVENTION: RAD added to ET. RESULTS AND LIMITATIONS: With a
      median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34%
      (95% confidence interval, 29-39%) and 17% (95% confidence interval, 13-22%) in
      the ET and ET + RAD arms respectively (p<0.001). Compared with the ET arm, the
      median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment
      with ET alone, age >=65 yr and increasing histology grade independently increased
      the risk of PCa-specific and overall mortality. Limitations include nonformal
      evaluation of comorbidity, the inability to calculate progression-free survival,
      and lack of information about salvage therapy and toxicity. CONCLUSIONS: In
      patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces
      the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone;
      the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results
      warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high
      risk PCa. PATIENT SUMMARY: Adding prostatic therapy to lifelong antiandrogen
      therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15
      yr after diagnosis.

PMID- 27025587
TI  - Reply to Egesta Lopci, Arturo Chiti, and Massimo Lazzeri's Letter to the Editor
      re: Laura Evangelista, Alberto Briganti, Stefano Fanti, et al. New Clinical
      Indications for 18F/11C-choline, New Tracers for Positron Emission Tomography and
      a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the
      Literature. Eur Urol 2016;70:161-75.

PMID- 27025588
TI  - Salvage Radiotherapy After Prostatectomy: Two Sides of the Coin.

PMID- 27025589
TI  - Seed-Mediated Hot-Injection Synthesis of Tiny Ag Nanocrystals on Nanoscale Solid
      Supports and Reaction Mechanism.
AB  - Controlling the size and shape of noble Ag nanocrystals (NCs) is of great
      interest because of their unique size- and shape-dependent properties, especially
      below 20 nm, and because of interesting applications in drug delivery, sensing,
      and catalysis. However, the high surface energy and tendency of these tiny NCs to
      aggregate deteriorates their unique properties and limits their applications. To
      avoid the aggregation of Ag NCs and improve their performance, we report a seed
      mediated hot injection approach to synthesize highly dispersed tiny Ag NCs on a
      nanosized solid CaCO3 support. This simple, low-cost, and effective chemical
      approach allows for synthesizing highly uniform Ag NCs (~10 nm) on the surface of
      presynthesized CaCO3 single NCs (~52 nm) without any aggregation of the Ag NCs.
      Viscose fibers were coated with the Ag@CaCO3 composite nanoparticles (NPs)
      produced, as well as with ~126 nm Ag NPs for reference. The Ag@CaCO3 composite
      NPs show excellent UV protection and antibacterial activity against Escherichia
      coli. In addition, they give a satin sheen gold to a dark gold color to the
      viscose fibers, while the Ag NPs (~126 nm) result in a silver color. The proposed
      synthesis approach is highly versatile and applicable for many other noble
      metals, like Au or Pt.

PMID- 27025590
TI  - Structure of the Cyclic Nucleotide-Binding Homology Domain of the hERG Channel
      and Its Insight into Type 2 Long QT Syndrome.
AB  - The human ether-a-go-go related gene (hERG) channel is crucial for the cardiac
      action potential by contributing to the fast delayed-rectifier potassium current.
      Mutations in the hERG channel result in type 2 long QT syndrome (LQT2). The hERG
      channel contains a cyclic nucleotide-binding homology domain (CNBHD) and this
      domain is required for the channel gating though molecular interactions with the
      eag domain. Here we present solution structure of the CNBHD of the hERG channel.
      The structural study reveals that the CNBHD adopts a similar fold to other KCNH
      channels. It is self-liganded and it contains a short beta-strand that blocks the
      nucleotide-binding pocket in the beta-roll. Folding of LQT2-related mutations in
      this domain was shown to be affected by point mutation. Mutations in this domain
      can cause protein aggregation in E. coli cells or induce conformational changes.
      One mutant-R752W showed obvious chemical shift perturbation compared with the
      wild-type, but it still binds to the eag domain. The helix region from the N
      terminal cap domain of the hERG channel showed unspecific interactions with the
      CNBHD. 

PMID- 27025594
TI  - Feasibility of an interactive electronic self-report tool for oral cancer therapy
      in an outpatient setting.
AB  - BACKGROUND: The introduction of oral anti-cancer agents provides a convenient
      administration route for chronic cancer treatment to outpatients. Health
      information technology through web-based applications or other electronic tools
      can offer a platform to improve treatment compliance, symptom management, and
      patient-provider communication. PURPOSE: The purposes of this study were to test
      the feasibility and clinical utility of an electronic self-report device
      (RemeCoach) for patients or their caregivers and to register and prospectively
      evaluate the quality of data generated. PATIENTS AND METHODS: Patients using
      Teysuno(r) (S-1) for advanced gastrointestinal carcinoma used a pre-programmed
      device in order to register compliance to treatment and six clinical parameters.
      Real-time data were collected onto a central platform, which processed the data
      by an algorithm. This algorithm stratified the data into different grades based
      on the Common Terminology Criteria for Adverse Events (CTCAE v4.0). RESULTS: From
      December 2013 to March 2014, 11 patients (5 men, 6 women) were enrolled.
      Compliance to the device was high, six patients (55 %) registered timely intake
      of medication (demonstrating >95 % treatment compliance). Agreement between
      patients' and clinicians' reported toxicity was substantial for nausea, but
      discrepant for fatigue, hand-foot syndrome, and mucositis. CONCLUSION: The use of
      an interactive self-report tool is feasible, reliable, and acceptable to
      outpatients. The RemeCoach and the algorithm devised will be further developed as
      an interactive patient-reported outcome (PRO) system, to improve early detection
      of side effects in an outpatient setting. Further studies are needed to confirm
      these data and to explore the relationship between optimal patient support and
      efficacy of treatment.

PMID- 27025595
TI  - Race-based disparities in loss of functional independence after hysterectomy for
      uterine cancer.
AB  - PURPOSE: Racial disparities in uterine cancer-related outcomes have been
      reported. The goal of this study was to determine if race, pre-operative body
      mass index (BMI), and medical comorbidities are predictors of loss of functional
      independence after hysterectomy for uterine cancer. METHODS: Loss of independence
      was defined as a change from pre-operative functional independence, to a post
      operative requirement of discharge to a post-care facility, or death within the
      first 30 days following uterine cancer surgery. Demographic factors,
      comorbidities, BMI, intra-operative and post-operative outcomes, and discharge
      status were abstracted from the 2011 and 2012 American College of Surgeons
      National Surgical Quality Improvement Program (NSQIP). Statistical analyses
      included multivariable logistic regression and Wald tests for interaction.
      RESULTS: A total of 4005 patients had uterine cancer and were functionally
      independent pre-operatively. After adjusting for clinical features and
      comorbidities, Black women were not significantly more likely to lose functional
      independence than non-Black women. However, a significant interaction (OR = 1.17,
      p < 0.001) was found between race and BMI for loss of functional independence.
      Interaction plots revealed worsening functional outcomes for Black women with BMI
      >40 but not in non-Blacks. CONCLUSIONS: The interaction suggests a 17 % increased
      odds of losing independence for each unit of BMI difference for Black uterine
      cancer patients, or 170 % increased odds of losing independence for a 10-point
      increase in BMI, given a linear association. To reduce the likelihood of losing
      post-operative functional independence, Black, high-BMI patients with or at risk
      for uterine cancer may especially benefit from weight loss or interventions to
      optimize physical function.

PMID- 27025596
TI  - PtrA/NINV, an alkaline/neutral invertase gene of Poncirus trifoliata, confers
      enhanced tolerance to multiple abiotic stresses by modulating ROS levels and
      maintaining photosynthetic efficiency.
AB  - BACKGROUND: Alkaline/neutral invertase (A/N-INV), an enzyme that hydrolyzes
      sucrose irreversibly into glucose and fructose, is essential for normal plant
      growth,development, and stress tolerance. However, the physiological and/or
      molecular mechanism underpinning the role of A/N-INV in abiotic stress tolerance
      is poorly understood. RESULTS: In this report, an A/N-INV gene (PtrA/NINV) was
      isolated from Poncirus trifoliata, a cold-hardy relative of citrus, and
      functionally characterized. PtrA/NINV expression levels were induced by cold,
      salt, dehydration, sucrose, and ABA, but decreased by glucose. PtrA/NINV was
      found to localize in both chloroplasts and mitochondria. Overexpression of
      PtrA/NINV conferred enhanced tolerance to multiple stresses, including cold, high
      salinity, and drought, as supported by lower levels of reactive oxygen species
      (ROS), reduced oxidative damages, decreased water loss rate, and increased
      photosynthesis efficiency, relative to wild-type (WT). The transgenic plants
      exhibited higher A/N-INV activity and greater reducing sugar content under normal
      and stress conditions. CONCLUSIONS: PtrA/NINV is an important gene implicated in
      sucrose decomposition, and plays a positive role in abiotic stress tolerance by
      promoting osmotic adjustment, ROS detoxification and photosynthesis efficiency.
      Thus, PtrA/NINV has great potential to be used in transgenic breeding for
      improvement of stress tolerance.

PMID- 27025597
TI  - Tumor lysis-like syndrome in a child during treatment for visceral leishmaniasis.
AB  - A 2.5-year-old girl was admitted due to splenomegaly and pancytopenia. Laboratory
      analysis revealed pancytopenia and hypergammaglobulinemia, and due to the absence
      of fever and the relevant clinical and hematological presentation the child was
      initially suspected for acute lymphoblastic leukemia. Bone marrow aspiration
      displayed macrophages and extracellular space containing Leishmania amastigotes.
      Visceral leishmaniasis diagnosis due to Leishmania infantum was confirmed by the
      presence of high titers of Leishmania antibodies and by PCR. The patient was
      successfully treated with liposomal amphotericin B but during the third post
      treatment day significant increases in the levels of serum uric acid, blood urea
      nitrogen, and phosphate were registered. The child was successfully treated with
      hydration and urine alkalization and resulted in full recovery of the metabolic
      abnormalities. 

PMID- 27025598
TI  - Association of SNP Haplotypes of HKT Family Genes with Salt Tolerance in Indian
      Wild Rice Germplasm.
AB  - BACKGROUND: Rice is one of the most important crops for global food security but
      its productivity is adversely affected by salt stress prevalent in about 30 % of
      the cultivated land. For developing salt-tolerant rice varieties through
      conventional breeding or biotechnological interventions, there is an urgent need
      to identify natural allelic variants that may confer salt tolerance. Here, 299
      wild rice accessions collected from different agro-climatic regions of India were
      evaluated during growth under salt stress. Of these 95 representative accessions
      were sequenced for members of HKT ion transporter family genes by employing Ion
      Torrent PGM sequencing platform. RESULTS: Haplotype analysis revealed haplotypes
      H5 and H1 of HKT1;5 and HKT2;3, respectively associated with high salinity
      tolerance. This is the first study of allele mining of eight members of HKT gene
      family from Indian wild rice reporting a salt tolerant allele of HKT2;3. HKT1;5
      also showed a salt tolerant allele from wild rice. Phylogenetic analysis based on
      the nucleotide sequences showed different grouping of the HKT family genes as
      compared to the prevailing protein sequence based classification. CONCLUSIONS:
      The salt tolerant alleles of the HKT genes from wild rice may be introgressed
      into modern high yielding cultivars to widen the existing gene pool and enhance
      rice production in the salt affected areas.

PMID- 27025599
TI  - Docosahexaenoic acid supplementation failed to attenuate chronic alcoholic fatty
      liver in mice.

PMID- 27025600
TI  - A new perspective of mechanosensitive pannexin-1 channels in cancer metastasis:
      clues for the treatment of other stress-induced diseases.

PMID- 27025601
TI  - Galectin-1 knockdown in carcinoma-associated fibroblasts inhibits migration and
      invasion of human MDA-MB-231 breast cancer cells by modulating MMP-9 expression.
AB  - Carcinoma-associated fibroblasts (CAFs) play central roles in facilitating tumor
      progression and metastasis in breast cancer. Galectin-1 (Gal-1), a marker of
      CAFs, was previously reported to be associated with tumorigenesis and metastasis
      of various types of tumors. The aim of this study is to investigate the role of
      Gal-1 in CAF-mediated breast cancer metastasis and its underlying molecular
      mechanisms. Our results showed that CAFs isolated from human breast tumor tissues
      expressed higher level of Gal-1 compared with paired normal fibroblasts, and the
      conditioned medium (CM) of CAFs significantly induced the migration and invasion
      of human MDA-MB-231 breast cancer cells. Knockdown of Gal-1 in CAFs dramatically
      inhibited CAF-CM-induced cell migration and invasion, probably by inhibiting the
      expression of matrix metalloprotein 9 (MMP-9). Our findings demonstrate that Gal
      1-regulated CAFs activation promotes breast cancer cell metastasis by
      upregulating MMP-9 expression, which indicated that Gal-1 in CAFs might be a
      potential novel target for breast cancer therapy. 

PMID- 27025602
TI  - Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF
      kappaB and MAPK in macrophages.
AB  - Inflammation is a response of body tissues to injury and infection. Compounds
      that can inhibit inflammation have been shown to have potential therapeutic
      clinical application. Gambogenic acid (GEA) has potent antitumor and anti
      inflammatory activities. Herein, the molecular mechanisms of GEA's anti
      inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated
      macrophage cells. The results showed that pretreatment with GEA could markedly
      inhibit interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor-alpha, IFN-beta,
      IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model.
      Furthermore, this drug significantly reduced the release of nitric oxide (NO),
      and impaired the protein level of inducible NO synthase and the cyclooxygenase 2.
      The finding also showed that the effect of GEA may be related to the suppression
      of the nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase
      (MAPK) signaling pathway. These results indicate that GEA could suppress LPS
      simulated inflammatory response partially by attenuating NO synthesis and NF
      kappaB and MAPK activation, suggesting that it may become a potent therapeutic
      agent for the treatment of inflammatory diseases. 

PMID- 27025603
TI  - Role of Neu-p11/luzindole in the regulation of insulin signaling pathways and
      insulin resistance.

PMID- 27025604
TI  - Bridging the gap between formal and experience-based knowledge for context-aware
      laparoscopy.
AB  - PURPOSE: Computer assistance is increasingly common in surgery. However, the
      amount of information is bound to overload processing abilities of surgeons. We
      propose methods to recognize the current phase of a surgery for context-aware
      information filtering. The purpose is to select the most suitable subset of
      information for surgical situations which require special assistance. METHODS: We
      combine formal knowledge, represented by an ontology, and experience-based
      knowledge, represented by training samples, to recognize phases. For this
      purpose, we have developed two different methods. Firstly, we use formal
      knowledge about possible phase transitions to create a composition of random
      forests. Secondly, we propose a method based on cultural optimization to infer
      formal rules from experience to recognize phases. RESULTS: The proposed methods
      are compared with a purely formal knowledge-based approach using rules and a
      purely experience-based one using regular random forests. The comparative
      evaluation on laparoscopic pancreas resections and adrenalectomies employs a
      consistent set of quality criteria on clean and noisy input. The rule-based
      approaches proved best with noisefree data. The random forest-based ones were
      more robust in the presence of noise. CONCLUSION: Formal and experience-based
      knowledge can be successfully combined for robust phase recognition.

PMID- 27025605
TI  - Estimating FLEimage distributions of manual fiducial localization in CT images.
AB  - PURPOSE: The fiducial localization error distribution (FLE) and fiducial
      configuration govern the application accuracy of point-based registration and
      drive target registration error (TRE) prediction models. The error of physically
      localizing patient fiducials ([Formula: see text]) is negligible when a
      registration probe matches the implanted screws with mechanical precision.
      Reliable trackers provide an unbiased estimate of the positional error ([Formula:
      see text]) with cheap repetitions. FLE further contains the localization error in
      the imaging data ([Formula: see text]), sampling of which in general is expensive
      and possibly biased. Finding the best techniques for estimating [Formula: see
      text] is crucial for the applicability of the TRE prediction methods. METHODS: We
      built a ground-truth (gt)-based unbiased estimator ([Formula: see text]) of
      [Formula: see text] from the samples collected in a virtual CT dataset in which
      the true locations of image fiducials are known by definition. Replacing true
      locations in [Formula: see text] by the sample mean creates a practical
      difference-to-mean (dtm)-based estimator ([Formula: see text]) that is applicable
      on any dataset. To check the practical validity of the dtm estimator, ten persons
      manually localized nine fiducials ten times in the virtual CT and the resulting
      [Formula: see text] and [Formula: see text] distributions were tested for
      statistical equality with a kernel-based two-sample test using the maximum mean
      discrepancy (MMD) (Gretton in J Mach Learn Res 13:723-773, 2012) statistics at
      [Formula: see text]. RESULTS: [Formula: see text] and [Formula: see text] were
      found (for most of the cases) not to be statistically significantly different;
      conditioning them on persons and/or screws however yielded statistically
      significant differences much more often. CONCLUSIONS: We conclude that [Formula:
      see text] is the best candidate (within our model) for estimating [Formula: see
      text] in homogeneous TRE prediction models. The presented approach also allows
      ground-truth-based numerical validation of [Formula: see text] estimators and
      (manual/automatic) image fiducial localization methods in phantoms with
      parameters similar to clinical datasets.

PMID- 27025606
TI  - Bystander effects and compartmental stress response to X-ray irradiation in L929
      cells.
AB  - Bystander effects are indirect consequences of radiation and many other stress
      factors. They occur in cells that are not directly exposed to these factors, but
      receive signals from affected cells either by gap junctions or by molecules
      released in the medium. Characterizing these effects and deciphering the
      underlying mechanisms involved in radiation-induced bystander effects are
      relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation
      0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei
      shortly after the treatment, through medium transfer and by co-cultures.
      Interestingly, bystander cells did not exhibit long-term adverse changes in
      viability. Evaluation of several compartmental stress markers (CHOP, BiP,
      mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at
      transcriptional level. We investigated the involvement of ROS and NO in this
      process by addition of specific scavengers of these molecules, DMSO or c-PTIO in
      the transferred medium. This approach proved that ROS but not NO is involved in
      the induction of lesions in the acceptor cells. These results indicate that L929
      cells are susceptible to stress effects of radiation-induced bystander signaling.

PMID- 27025607
TI  - Subjective memory complaints in Italian elderly with mild cognitive impairment:
      implication of psychological status.
AB  - Subjective cognitive and memory complaints (SMC) are common in later life and are
      considered an indicator for progression to cognitive decline. The aim of the
      present study was to identify the relationship among SMC, neuropsychiatric
      symptoms and psychological aspects in elderly subjects with mild cognitive
      impairment (MCI) as well as to analyse the effect on SMC of a comprehensive
      cognitive training. Data from a sample of 94 patients enrolled in 'My Mind
      Project' (Grant No. 154/GR-2009-1584108) were collected. The study evidenced that
      depression was a significant predictor of SMC and that after the training, the
      number of subjects with SMC was significantly reduced in the experimental group
      in comparison to the control one. These results suggest that the participation in
      cognitive stimulation protocols may improve the perception of SMC in subjects
      with MCI. 

PMID- 27025608
TI  - A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical
      activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients
      with advanced solid tumors.
AB  - PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation
      inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase
      1 study evaluated the safety and tolerability, pharmacokinetics, and clinical
      activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies
      in a first-in-Asian study setting. METHODS: VS-6063 was administered orally twice
      daily (b.i.d.) in 21-day cycles to cohorts of three subjects each with a standard
      3 + 3 dose-escalation design until disease progression or unacceptable toxicity.
      Blood samples for pharmacokinetics were collected on Day 1 and 15. The
      assessments were performed using CTCAE v4.0 for adverse events (AEs), and the
      Response Evaluation Criteria In Solid Tumors, version v1.1 (RECIST v1.1) for
      tumor response. RESULTS: Nine patients were treated across three dose levels (200
      600 mg BID). No dose-limiting toxicities were observed at any dose level. Most
      frequent treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia,
      fatigue, decreased appetite, and diarrhea. Only one subject in the 200 mg BID
      cohort experienced reversible and transient Grade 3 unconjugated
      hyperbilirubinemia. PK analyses confirmed that the exposure at the recommended
      Phase 2 dose (RP2D) of 400 mg BID was comparable with exposures previously
      reported in non-Japanese subjects. Durable stable disease of approximately 24
      weeks was confirmed in two subjects (malignant mesothelioma and rectal cancer).
      CONCLUSIONS: VS-6063 was well tolerated at all dose levels investigated in this
      first-in-Asian study. These data support the administration of VS-6063 to
      Japanese subjects at the RP2D in clinical trials involving solid tumor
      malignancies.

PMID- 27025609
TI  - Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non
      parametric approach.
AB  - AIMS: Nevirapine is the first non-nucleoside reverse-transcriptase inhibitor
      approved and is widely used in combination therapy to treat HIV-1 infection. The
      pharmacokinetics of nevirapine was extensively studied in various populations
      with a parametric approach. Hence, this study was aimed to determine population
      pharmacokinetic parameters in Malaysian HIV-infected patients with a non
      parametric approach which allows detection of outliers or non-normal distribution
      contrary to the parametric approach. METHODS: Nevirapine population
      pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112
      patients were included in the model building and validation analysis. Evaluation
      of the model was based on a visual inspection of observed versus predicted
      (population and individual) concentrations and plots weighted residual error
      versus concentrations. Accuracy and robustness of the model were evaluated by
      visual predictive check (VPC). The median parameters' estimates obtained from the
      final model were used to predict individual nevirapine plasma area-under-curve
      (AUC) in the validation dataset. The Bland-Altman plot was used to compare the
      AUC predicted with trapezoidal AUC. RESULTS: The median nevirapine clearance was
      of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of
      distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one
      compartmental with first-order absorption model and a lag-time. Weighted
      residuals for the model selected were homogenously distributed over the
      concentration and time range. The developed model adequately estimated AUC.
      CONCLUSIONS: In conclusion, a model to describe the pharmacokinetics of
      nevirapine was developed. The developed model adequately describes nevirapine
      population pharmacokinetics in HIV-infected patients in Malaysia.

PMID- 27025610
TI  - Cortactin and Exo70 mediated invasion of hepatoma carcinoma cells by MMP-9
      secretion.
AB  - This study was aimed to evaluate the regulation mechanism of cortactin (CTTN) on
      matrix metalloproteinases 9 (MMP-9) and its relations with Exo70 in invasion of
      hepatoma carcinoma (HCC) cells. The expression levels of CTTN, Exo70 and MMP-9
      were detected in normal hepatocytes and various HCC cells by real-time PCR. Then
      the migration and invasion ability of these cells was revealed by scratch and
      invasion assay. The effects of CTTN on MMP-9 and the ability of migration and
      invasion were evaluated by silence and overexpress CTTN. During this process, the
      expression of CTTN was detected by Western blot, the activity and concentration
      of MMP-9 in supernatant of culture medium was detected by zymography and ELISA
      assay. Besides, Exo70 was also inhibited to reveal its effects on MMP-9 and the
      migration and invasion ability of LM3. Increased expression of CTTN, MMP-9,
      Exo70, reduced scratch area and increased puncture cell numbers were found in HCC
      cells (p < 0.05). The expression of CTTN was significantly correlated with Exo70
      and the migration and invasion ability of HCC (p < 0.05). In addition, the
      activity and concentration of MMP-9 were significantly affected by the expression
      level of CTTN, while the expression of MMP-9 was not influenced. Besides, Exo70
      si also exhibited significantly inhibition effects on the activity and
      concentration of MMP-9 and puncture cell numbers (p < 0.05). A synergistic
      reaction may exhibited on CTTN and Exo70, which could mediate the secretion of
      MMPs thereby regulate tumor invasion.

PMID- 27025611
TI  - The Sensorium: Psychophysiological Evaluation of Responses to a Multimodal
      Neurofeedback Environment.
AB  - The Sensorium is a multimodal neurofeedback environment that reflects a person's
      physiological state by presenting physiological signals via orchestral sounds
      from a speaker and multi-coloured lights projected onto a white surface. The
      software manages acquisition, real-time processing, storage, and sonification of
      various physiological signals such as the electroencephalogram (EEG) or
      electrocardiogram (ECG). Each of the 36 participants completed 6 interventional
      conditions consisting of three different Sensorium-phases with EEG and ECG
      feedback, a mindfulness meditation, a guided body scan exercise, and a Pseudo
      Sensorium using pre-recorded data that did not reflect the subject's own
      physiology. During all phases EEG, ECG, skin conductance, and respiration were
      recorded. A feedback questionnaire assessed the participants' subjective reports
      of changes in well-being, perception, and life-spirit. The results indicate that
      the Sensorium sessions were not statistically inferior compared to their
      corresponding active control conditions with respect to improvements in
      subjective reports concerning well-being and perception. Additionally, the
      Sensorium was rated as being a more extraordinary experience, as compared to
      meditation. During the Sensorium conditions the EEG showed lower levels of theta2
      (7-8.5 Hz), alpha (9-12 Hz) and beta (12.5-25 Hz) activity. Since participants
      reported benefit from the Sensorium experience regardless of any prior experience
      with meditation, we propose this novel method of meditative and extraordinary
      self-experience to be utilized as a modern alternative to more traditional forms
      of meditation.

PMID- 27025614
TI  - Augmentation of Cationic Antimicrobial Peptide Production with Histone
      Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections.
AB  - The emergence of antibiotic resistance seriously threatens our ability to treat
      many common and medically important bacterial infections. Novel therapeutics are
      needed that can be used alone or in conjunction with antibiotics. Cationic
      antimicrobial peptides (CAMPs) are important effectors of the host innate defense
      that exhibit broad-spectrum activity against a wide range of microorganisms.
      CAMPs are carried within phagocytic granules and are constitutively or inducibly
      expressed by multiple cell types, including epithelial cells. The role of histone
      modification enzymes, specifically the histone deacetylases (HDAC), in down
      regulating the transcription of CAMP-encoding genes is increasingly appreciated
      as is the capacity of HDAC inhibitors (HDACi) to block the action of HDACs to
      increase CAMP expression. The use of synthetic and natural HDACi molecules to
      increase CAMPs on mucosal surfaces, therefore, has potential therapeutic
      applications. Here, we review host and pathogen regulation of CAMP expression
      through the induction of HDACs and assess the therapeutic potential of natural
      and synthetic HDACi based on evidence from tissue culture systems, animal models,
      and clinical trials. 

PMID- 27025612
TI  - The Role of Antifungals against Candida Biofilm in Catheter-Related Candidemia.
AB  - Catheter-related bloodstream infection (C-RBSI) is one of the most frequent
      nosocomial infections. It is associated with high rates of morbidity and
      mortality. Candida spp. is the third most common cause of C-RBSI after coagulase
      negative staphylococci and Staphylococcus aureus and is responsible for
      approximately 8% of episodes. The main cause of catheter-related candidemia is
      the ability of some Candida strains-mainly C. albicans and C. parapsilosis-to
      produce biofilms. Many in vitro and in vivo models have been designed to assess
      the activity of antifungal drugs against Candida biofilms. Echinocandins have
      proven to be the most active antifungal drugs. Potential options in situations
      where the catheter cannot be removed include the combination of systemic and lock
      antifungal therapy. However, well-designed and -executed clinical trials must be
      performed before firm recommendations can be issued. 

PMID- 27025615
TI  - NETs and CF Lung Disease: Current Status and Future Prospects.
AB  - Cystic Fibrosis (CF) is the most common fatal monogenic disease among Caucasians.
      While CF affects multiple organ systems, the principle morbidity arises from
      progressive destruction of lung architecture due to chronic bacterial infection
      and inflammation. It is characterized by an innate immune defect that results in
      colonization of the airways with bacteria such as Staphylococcus aureus and
      Pseudomonas aeruginosa from an early age. Within the airway microenvironment the
      innate immune cells including epithelial cells, neutrophils, and macrophages have
      all been implicated in the host defense defect. The neutrophil, however, is the
      principal effector cell facilitating bacterial killing, but also participates in
      lung damage. This is evidenced by a disproportionately elevated neutrophil burden
      in the airways and increased neutrophil products capable of tissue degradation,
      such as neutrophil elastase. The CF airways also contain an abundance of nuclear
      material that may be originating from neutrophils. Neutrophil extracellular traps
      (NETs) are the product of a novel neutrophil death process that involves the
      expulsion of nuclear material embedded with histones, proteases, and
      antimicrobial proteins and peptides. NETs have been postulated to contribute to
      the bacterial killing capacity of neutrophils, however they also function as a
      source of proteases and other neutrophil products that may contribute to lung
      injury. Targeting nuclear material with inhaled DNase therapy improves lung
      function and reduces exacerbations in CF and some of these effects may be due to
      the degradation of NETs. We critically discuss the evidence for an antimicrobial
      function of NETs and their potential to cause lung damage and inflammation. We
      propose that CF animal models that recapitulate the human CF phenotype such as
      the CFTR(-/-) pig may be useful in further elucidating a role for NETs. 

PMID- 27025616
TI  - Genomic, Transcriptomic and Metabolomic Studies of Two Well-Characterized,
      Laboratory-Derived Vancomycin-Intermediate Staphylococcus aureus Strains Derived
      from the Same Parent Strain.
AB  - Complete genome comparisons, transcriptomic and metabolomic studies were
      performed on two laboratory-selected, well-characterized vancomycin-intermediate
      Staphylococcus aureus (VISA) derived from the same parent MRSA that have changes
      in cell wall composition and decreased autolysis. A variety of mutations were
      found in the VISA, with more in strain 13136p(-)m+V20 (vancomycin MIC = 16 ug/mL)
      than strain 13136p(-)m+V5 (MIC = 8 ug/mL). Most of the mutations have not
      previously been associated with the VISA phenotype; some were associated with
      cell wall metabolism and many with stress responses, notably relating to DNA
      damage. The genomes and transcriptomes of the two VISA support the importance of
      gene expression regulation to the VISA phenotype. Similarities in overall
      transcriptomic and metabolomic data indicated that the VISA physiologic state
      includes elements of the stringent response, such as downregulation of protein
      and nucleotide synthesis, the pentose phosphate pathway and nutrient transport
      systems. Gene expression for secreted virulence determinants was generally
      downregulated, but was more variable for surface-associated virulence
      determinants, although capsule formation was clearly inhibited. The importance of
      activated stress response elements could be seen across all three analyses, as in
      the accumulation of osmoprotectant metabolites such as proline and glutamate.
      Concentrations of potential cell wall precursor amino acids and glucosamine were
      increased in the VISA strains. Polyamines were decreased in the VISA, which may
      facilitate the accrual of mutations. Overall, the studies confirm the wide
      variability in mutations and gene expression patterns that can lead to the VISA
      phenotype. 

PMID- 27025617
TI  - Purification of a Multidrug Resistance Transporter for Crystallization Studies.
AB  - Crystallization of integral membrane proteins is a challenging field and much
      effort has been invested in optimizing the overexpression and purification steps
      needed to obtain milligram amounts of pure, stable, monodisperse protein sample
      for crystallography studies. Our current work involves the structural and
      functional characterization of the Escherichia coli multidrug resistance
      transporter MdtM, a member of the major facilitator superfamily (MFS). Here we
      present a protocol for isolation of MdtM to increase yields of recombinant
      protein to the milligram quantities necessary for pursuit of structural studies
      using X-ray crystallography. Purification of MdtM was enhanced by introduction of
      an elongated His-tag, followed by identification and subsequent removal of
      chaperonin contamination. For crystallization trials of MdtM, detergent screening
      using size exclusion chromatography determined that decylmaltoside (DM) was the
      shortest-chain detergent that maintained the protein in a stable, monodispersed
      state. Crystallization trials of MdtM performed using the hanging-drop diffusion
      method with commercially available crystallization screens yielded 3D protein
      crystals under several different conditions. We contend that the purification
      protocol described here may be employed for production of high-quality protein of
      other multidrug efflux members of the MFS, a ubiquitous, physiologically and
      clinically important class of membrane transporters. 

PMID- 27025619
TI  - Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A
      Meta-analysis and Systematic Review.
AB  - Clostridium difficile infections are a global clinical concern and are one of the
      leading causes of nosocomial outbreaks. Preventing these infections has benefited
      from multidisciplinary infection control strategies and new antibiotics, but the
      problem persists. Probiotics are effective in preventing antibiotic-associated
      diarrhea and may also be a beneficial strategy for C. difficile infections, but
      randomized controlled trials are scarce. This meta-analysis pools 21 randomized,
      controlled trials for primary prevention of C. difficile infections (CDI) and
      four trials for secondary prevention of C. difficile recurrences and assesses the
      efficacy of specific probiotic strains. Four probiotics significantly improved
      primary CDI prevention: (Saccharomyces boulardii, Lactobacillus casei DN114001, a
      mixture of L. acidophilus and Bifidobacterium bifidum, and a mixture of L.
      acidophilus, L. casei and L. rhamnosus). None of the tested probiotics
      significantly improved secondary prevention of CDI. More confirmatory randomized
      trials are needed to establish if probiotics are useful for preventing C.
      difficile infections. v. 

PMID- 27025618
TI  - Host Defense Peptides from Asian Frogs as Potential Clinical Therapies.
AB  - Host defense peptides (HDPs) are currently major focal points of medical research
      as infectious microbes are gaining resistance to existing drugs. They are
      effective against multi-drug resistant pathogens due to their unique primary
      target, biological membranes, and their peculiar mode of action. Even though HDPs
      from 60 Asian frog species belonging to 15 genera have been characterized,
      research into these peptides is at a very early stage. The purpose of this review
      is to showcase the status of peptide research in Asia. Here we provide a summary
      of HDPs from Asian frogs. 

PMID- 27025620
TI  - Identification of Anti-Persister Activity against Uropathogenic Escherichia coli
      from a Clinical Drug Library.
AB  - Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but
      current antibiotics do not always effectively clear the persistent infection. To
      identify drugs that eliminate uropathogenic E. coli persisters, we screened a
      clinical drug library consisting of 1524 compounds using high throughput drug
      exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB
      plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin,
      moxifloxacin and gatifloxacin, enrofloxacin and sarafloxacin, octodrine,
      clofoctol, dibekacin, cephalosporin C, pazufloxacin, streptomycin and neomycin),
      which had high anti-persister activity. Among them, tosufloxacin and colistin had
      the highest anti-persister activity and could completely eradicate E. coli
      persisters in 3 days in vitro while the current UTI antibiotics failed to do so.
      Our findings may have implications for the development of a more effective
      treatment for UTIs. 

PMID- 27025621
TI  - The Antimicrobial Stewardship Approach to Combating Clostridium Difficile.
AB  - Clostridium difficile remains a major public health threat and continues to
      contribute to excess morbidity, mortality and healthcare costs. Antimicrobial
      stewardship programs have demonstrated success in combating C. difficile,
      primarily through antibiotic restrictive strategies. As the incidence and
      prevalence of C. difficile associate disease continues to increase both in the
      hospital and community setting, additional stewardship approaches are needed.
      This manuscript reviews stewardship interventions that have been successful
      against C. difficile associated disease and proposes future tactics that
      antimicrobial stewardship programs may employ to develop a more global approach
      to combat this difficult pathogen. 

PMID- 27025622
TI  - Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with
      Clostridium Difficile Infection.
AB  - Clostridium difficile infection (CDI) is known to be associated with prior
      exposure to many classes of antibiotics. Standard therapy for CDI (i.e.,
      metronidazole and vancomycin) is associated with high recurrence rates. Although
      tetracycline derivatives such as tetracycline, doxycycline or tigecycline are not
      the standard therapeutic choices for CDI, they may serve as an alternative or a
      component of combination therapy. Previous tetracycline or doxycycline usage had
      been shown to have less association with CDI development. Tigecycline, a broad
      spectrum glycylcycline with potency against many gram-positive or gram-negative
      pathogens, had been successfully used to treat severe or refractory CDI. The in
      vitro susceptibility of C. difficile clinical isolates to tigecycline in many
      studies showed low minimal inhibitory concentrations. Tigecycline can suppress in
      vitro toxin production in both historical and hypervirulent C. difficile strains
      and reduce spore production in a dose-dependent manner. Tetracycline compounds
      such as doxycycline, minocycline, and tigecycline possess anti-inflammatory
      properties that are independent of their antibiotic activity and may contribute
      to their therapeutic effect for CDI. Although clinical data are limited,
      doxycycline is less likely to induce CDI, and tigecycline can be considered one
      of the therapeutic choices for severe or refractory CDI. 

PMID- 27025623
TI  - Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization
      and Infection.
AB  - Clostridium difficile infection (CDI) is the most important cause of nosocomial
      diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the
      structure and diversity of the indigenous intestinal microbiota. These
      alterations often impair colonization resistance, allowing the establishment and
      proliferation of C. difficile in the gut. Studies involving animal models have
      begun to decipher the precise mechanisms by which the intestinal microbiota
      mediates colonization resistance against C. difficile and numerous investigations
      have described gut microbiota alterations associated with C. difficile
      colonization or infection in human subjects. Fecal microbiota transplantation
      (FMT) is a highly effective approach for the treatment of recurrent CDI that
      allows the restoration of a healthy intestinal ecosystem via infusion of fecal
      material from a healthy donor. The recovery of the intestinal microbiota after
      FMT has been examined in a few reports and work is being done to develop custom
      bacterial community preparations that could be used as a replacement for fecal
      material. 

PMID- 27025624
TI  - Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile
      Infections and Beyond.
AB  - Fecal Microbiota Transplantation (FMT) methodology has been progressively refined
      over the past several years. The procedure has an extensive track record of
      success curing Clostridium difficile infection (CDI) with remarkably few adverse
      effects. It achieves similar levels of success whether the CDI occurs in the
      young or elderly, previously normal or profoundly ill patients, or those with CDI
      in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we
      learned that using the procedure in other gastrointestinal (GI) diseases, such as
      IBD without CDI, generally fails to effect cure. To improve results in treating
      other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs)
      will be required to address questions about mechanisms operating within
      particular diseases. Availability of orally deliverable FMT products, such as
      capsules containing lyophilised fecal microbiota, will simplify CDI treatment and
      open the door to convenient, prolonged FMT delivery to the GI tract and will
      likely deliver improved results in both CDI and non-CDI diseases. 

PMID- 27025626
TI  - Antimicrobial Stewardship Intervention and Feedback to Infectious Disease
      Specialists: A Case Study in High-Dose Daptomycin.
AB  - Infectious Diseases specialists have used high-dose daptomycin (>=6 mg/kg/day) in
      select patients with difficult to treat methicillin-resistant Staphylococcus
      aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infections to optimize
      outcomes. Antimicrobial stewardship programs enforce antimicrobial formulary
      restrictions; however, interventions specifically aimed at Infectious Disease
      specialists can be particularly challenging. The purpose of this study was to
      create a high-dose daptomycin algorithm for Infectious Disease specialists that
      are consistent with best-practices. Daptomycin prescribing habits pre- and post
      daptomycin algorithm implementation were evaluated using a quasi-experimental
      study design. Patients were included if >=18 years of age and received daptomycin
      for >=48 h. Patients were excluded if daptomycin was initiated on an outpatient
      setting. During the 12-month pre-intervention phase, 112 patients were included,
      with 73 patients in the 12-month post-intervention phase. A statistically
      significant decrease in the mean daptomycin dose from 9.01 mg/kg to 7.51 mg/kg (p
      < 0.005) was observed, resulting in an annual drug cost-savings of over $75,000
      without adversely affecting readmission rates due to infection. Creation of a
      daptomycin algorithm with consideration of pathogen, disease state, and prior
      treatment, is an effective means of influencing prescribing habits of Infectious
      Disease specialists. 

PMID- 27025627
TI  - A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active
      against Staphylococcus aureus Persisters.
AB  - To identify effective compounds that are active against Staphylococcus aureus (S.
      aureus) persisters, we screened a clinical drug library consisting of 1524
      compounds and identified six drug candidates that had anti-persister activity:
      tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and
      chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister
      activity, which could completely eradicate S. aureus persisters within 2 days in
      vitro. Clinafloxacin ranked the second with very few persisters surviving the
      drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin
      that had high activity against persisters contained at the N-1 position the 2,4
      difluorophenyl group, which is absent in other less active quinolones and may be
      associated with the high anti-persister activity. Further studies are needed to
      evaluate tosufloxacin in animal models and to explain its unique activity against
      bacterial persisters. Our findings may have implications for improved treatment
      of persistent bacterial infections. 

PMID- 27025625
TI  - Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile:
      Potential Consequences for Induction, Treatment, and Recurrence of C. difficile
      Infection.
AB  - Clostridium difficile infection (CDI) remains a substantial burden on healthcare
      systems and is likely to remain so given our reliance on antimicrobial therapies
      to treat bacterial infections, especially in an aging population in whom multiple
      co-morbidities are common. Antimicrobial agents are a key component in the
      aetiology of CDI, both in the establishment of the infection and also in its
      treatment. The purpose of this review is to summarise the role of antimicrobial
      agents in primary and recurrent CDI; assessing why certain antimicrobial classes
      may predispose to the induction of CDI according to a balance between
      antimicrobial activity against the gut microflora and C. difficile. Considering
      these aspects of CDI is important in both the prevention of the infection and in
      the development of new antimicrobial treatments. 

PMID- 27025628
TI  - Colonization Resistance of the Gut Microbiota against Clostridium difficile.
AB  - Antibiotics strongly disrupt the human gut microbiota, which in consequence loses
      its colonization resistance capacity, allowing infection by opportunistic
      pathogens such as Clostridium difficile. This bacterium is the main cause of
      antibiotic-associated diarrhea and a current problem in developed countries,
      since its incidence and severity have increased during the last years.
      Furthermore, the emergence of antibiotic resistance strains has reduced the
      efficiency of the standard treatment with antibiotics, leading to a higher rate
      of relapses. Here, we review recent efforts focused on the impact of antibiotics
      in the gut microbiome and their relationship with C. difficile colonization, as
      well as, in the identification of bacteria and mechanisms involved in the
      protection against C. difficile infection. Since a healthy gut microbiota is able
      to avoid pathogen colonization, restoration of the gut microbiota seems to be the
      most promising approach to face C. difficile infection, especially for recurrent
      cases. Therefore, it would be possible to design probiotics for patients
      undergoing antimicrobial therapies in order to prevent or fight the expansion of
      the pathogen in the gut ecosystem. 

PMID- 27025629
TI  - Short, Synthetic Cationic Peptides Have Antibacterial Activity against
      Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with
      Antibiotics.
AB  - Multicellular organisms are constantly exposed to a multitude of pathogenic
      microbes. Infection is inhibited in vivo by the innate and adaptive immune
      system. Mycobacterium species have emerged that are resistant to most
      antibiotics. We identified several naturally occurring cationic antimicrobial
      peptides that were active at low micromolar concentrations against Mycobacterium
      smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied
      against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin
      NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA
      1A and ATRA-2) containing variations of a repeated motif within NA-CATH were
      tested for their activity against M. smegmatis along with a short synthetic
      peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized
      that these smaller synthetic peptides may demonstrate antimicrobial effectiveness
      with shorter length (and at less cost), making them strong potential candidates
      for development into broad-spectrum antimicrobial compounds or use in combination
      with antibiotics. These peptides have antimicrobial activity with EC50 ranging
      from 0.05 to 1.88 MUg/mL against Mycobacterium smegmatis. The ATRA-1A short
      peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 =
      0.05 MUg/mL). High bactericidal activity correlated with bacterial membrane
      depolarization and permeabilization activities. The efficacy of the peptides was
      further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs
      were determined by the microdilution method. The peptide mCRAMP showed the best
      MIC activity at 15.6 MUg/mL. Neither of the effective short synthetic peptides
      demonstrated synergy with the antibiotic rifampicin, although both demonstrated
      synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and
      mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic
      polymyxin B displayed synergism with LL-37, ATRA-1A, and hBD3-Pep4. In further
      studies, polymyxin B synergized with LL-37, ATRA-1A, and hBD3-Pep4 while
      Rifampicin synergized with LL-37 and mCRAMP for intracellular killing of
      mycobacteria residing inside macrophages. These studies provide the foundation
      for the potential development of synthetic cationic antimicrobial peptides with
      activity against mycobacteria. 

PMID- 27025630
TI  - Multidrug Efflux Systems in Microaerobic and Anaerobic Bacteria.
AB  - Active drug efflux constitutes an important mechanism of antibiotic and multidrug
      resistance in bacteria. Understanding the distribution, expression, and
      physiological functions of multidrug efflux pumps, especially under
      physiologically and clinically relevant conditions of the pathogens, is the key
      to combat drug resistance. In animal hosts, most wounded, infected and inflamed
      tissues display low oxygen tensions. In this article, we summarize research
      development on multidrug efflux pumps in the medicinally relevant microaerobic
      and anaerobic pathogens and their implications in the effort to combat drug
      resistant infections. 

PMID- 27025631
TI  - Identification of Additional Anti-Persister Activity against Borrelia burgdorferi
      from an FDA Drug Library.
AB  - Lyme disease is a leading vector-borne disease in the United States. Although the
      majority of Lyme patients can be cured with standard 2-4 week antibiotic
      treatment, 10%-20% of patients continue to suffer from prolonged post-treatment
      Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting
      organisms not killed by current Lyme antibiotics may be involved. In our previous
      study, we screened an FDA drug library and reported 27 top hits that showed high
      activity against Borrelia persisters. In this study, we present the results of an
      additional 113 active hits that have higher activity against the stationary phase
      B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial
      agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics)
      used for treating other infections were found to have better activity than the
      current Lyme antibiotics. These include antibacterials such as rifamycins (3
      formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs
      (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors
      carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole,
      mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents
      zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue,
      and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar
      emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone,
      pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non
      infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic
      acid, and dextrorphan tartrate, that act on the glutathione/gamma-glutamyl
      pathway involved in protection against free radical damage, and also the
      antidepressant drug indatraline, were found to have high activity against
      stationary phase B. burgdorferi. Among the active hits, agents that affect cell
      membranes, energy production, and reactive oxygen species production are more
      active against the B. burgdorferi persisters than the commonly used antibiotics
      that inhibit macromolecule biosynthesis. Future studies are needed to evaluate
      and optimize the promising active hits in drug combination studies in vitro and
      also in vivo in animal models. These studies may have implications for developing
      more effective treatments of Lyme disease. 

PMID- 27025632
TI  - A Review of Management of Clostridium difficile Infection: Primary and
      Recurrence.
AB  - Clostridium difficile infection (CDI) is a potentially fatal illness, especially
      in the elderly and hospitalized individuals. The recurrence and rates of CDI are
      increasing. In addition, some cases of CDI are refractory to the currently
      available antibiotics. The search for improved modalities for the management of
      primary and recurrent CDI is underway. This review discusses the current
      antibiotics, fecal microbiota transplantation (FMT) and other options such as
      immunotherapy and administration of non-toxigenic Clostridium difficile (CD) for
      the management of both primary and recurrent CDI. 

PMID- 27025633
TI  - An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin
      Resistant Staphylococcus aureus (MRSA).
AB  - The lack of new antibacterial drugs entering the market and their misuse have
      resulted in the emergence of drug-resistant bacteria, posing a major health
      crisis worldwide. In particular, meticillin-resistant Staphylococcus aureus
      (MRSA), a pathogen responsible for numerous human infections, has become endemic
      in hospitals worldwide. Drug repurposing, the finding of new therapeutic
      indications for approved drugs, is deemed a plausible solution to accelerate drug
      discovery and development in this area. Towards this end, we screened 1163 drugs
      approved by the Food and Drug Administration (FDA) for bioactivities against MRSA
      in a 10 MUM single-point assay. After excluding known antibiotics and
      antiseptics, six compounds were identified and their MICs were determined against
      a panel of clinical MRSA strains. A toxicity assay using human keratinocytes was
      also conducted to gauge their potential for repurposing as topical agents for
      treating MRSA skin infections. 

PMID- 27025634
TI  - Learning Processes and Trajectories for the Reduction of Antibiotic Use in Pig
      Farming: A Qualitative Approach.
AB  - Since 2011, French public policy has been encouraging a reduction in the use of
      antibiotics in animal farming. The aim of this article is to look at how some
      farms have already managed to lower their consumption of antibiotics, and to
      highlight the levers of change in farming health practices. Our research uses a
      qualitative study based on 21 semi-structured interviews with farmers and
      veterinarians in the French pig-farming sector. We use the notion of "trajectory
      of change" to examine, over time, the intersection of the technical, economic,
      social and organisational determinants which affect the reduced use of
      antibiotics. The "learning process" concept makes it possible to take account of
      the way in which the actors assimilate, appropriate and implement new health
      practices. We have identified three interdependent levels of learning: technical
      learning, cognitive learning and organisational learning. 

PMID- 27025635
TI  - Miniaturized Antimicrobial Susceptibility Test by Combining Concentration
      Gradient Generation and Rapid Cell Culturing.
AB  - Effective treatment of bacterial infection relies on timely diagnosis and proper
      prescription of antibiotic drugs. The antimicrobial susceptibility test (AST) is
      one of the most crucial experimental procedures, providing the baseline
      information for choosing effective antibiotic agents and their dosages.
      Conventional methods, however, require long incubation times or significant
      instrumentation costs to obtain test results. We propose a lab-on-a-chip approach
      to perform AST in a simple, economic, and rapid manner. Our assay platform
      miniaturizes the standard broth microdilution method on a microfluidic device (20
      * 20 mm) that generates an antibiotic concentration gradient and delivers
      antibiotic-containing culture media to eight 30-nL chambers for cell culture.
      When tested with 20 MUL samples of a model bacterial strain (E. coli ATCC 25922)
      treated with ampicillin or streptomycin, our method allows for the determination
      of minimum inhibitory concentrations consistent with the microdilution test in
      three hours, which is almost a factor of ten more rapid than the standard method.

PMID- 27025636
TI  - Antibiotic Stewardship Initiatives as Part of the UK 5-Year Antimicrobial
      Resistance Strategy.
AB  - Antibiotic use is a major driver for the emergence and spread of antibiotic
      resistance. Antimicrobial stewardship programmes aim to improve antibiotic
      prescribing with the objectives of optimizing clinical outcomes while at the same
      time minimizing unintended consequences such as adverse effects and the selection
      of antibiotic resistance. In 2013, a five-year national strategy for tackling
      antimicrobial resistance was published in the UK. The overarching goal of the
      strategy is to slow the development and spread of resistance and to this end it
      has three strategic aims, namely to improve knowledge and understanding of
      resistance, to conserve and steward the effectiveness of existing treatments and
      to stimulate the development of new antibiotics, diagnostics and novel therapies.
      This article reviews the antimicrobial stewardship activities included in the
      strategy and describes their implementation and evaluation. 

PMID- 27025637
TI  - Induction of Antimicrobial Resistance in Escherichia coli and Non-Typhoidal
      Salmonella Strains after Adaptation to Disinfectant Commonly Used on Farms in
      Vietnam.
AB  - In Vietnam, commercial disinfectants containing quaternary ammonium compounds
      (QACs) are commonly used in pig and poultry farms to maintain hygiene during
      production. We hypothesized that sustained exposure to sub-bactericidal
      concentrations of QAC-based disinfectants may result in increased levels of
      antimicrobial resistance (AMR) among Enterobacteriacea due to the increase of
      efflux pump expression. To test this hypothesis we exposed six antimicrobial
      susceptible Escherichia coli (E. coli) and six antimicrobial-susceptible non
      typhoidal Salmonella (NTS) isolates to increasing concentrations of a commonly
      used commercial disinfectant containing a mix of benzalkonium chloride and
      glutaraldehyde. Over the 12-day experiment, strains exhibited a significant
      change in their minimum inhibitory concentration (MIC) of the disinfectant
      product (mean increase of 31% (SD +/- 40)) (p = 0.02, paired Wilcoxon test).
      Increases in MIC for the disinfectant product were strongly correlated with
      increases in MIC (or decreases in inhibition zone) for all antimicrobials
      (Pearson's correlation coefficient 0.71-0.83, all p < 0.01). The greatest
      increases in MIC (or decreases in inhibition zone) were observed for ampicillin,
      tetracycline, ciprofloxacin, and chloramphenicol, and the smallest for
      gentamicin, trimethoprim/sulphamethoxazole. The treatment of 155 representative
      E. coli isolates from farmed and wild animals in the Mekong Delta (Vietnam) with
      phenyl-arginine beta-naphthylamide (PAbetaN), a generic efflux pump inhibitor,
      resulted in reductions in the prevalence of AMR ranging from 0.7% to 3.3% in
      these organisms, indicating a small contribution of efflux pumps on the observed
      prevalence of AMR on farms. These results suggest that the mass usage of
      commercial disinfectants, many of which contain QACs, is potentially a
      contributing factor on the generation and maintenance of AMR in animal production
      in Vietnam. 

PMID- 27025638
TI  - Core Steps of Membrane-Bound Peptidoglycan Biosynthesis: Recent Advances, Insight
      and Opportunities.
AB  - We are entering an era where the efficacy of current antibiotics is declining,
      due to the development and widespread dispersion of antibiotic resistance
      mechanisms. These factors highlight the need for novel antimicrobial discovery. A
      large number of antimicrobial natural products elicit their effect by directly
      targeting discrete areas of peptidoglycan metabolism. Many such natural products
      bind directly to the essential cell wall precursor Lipid II and its metabolites,
      i.e., preventing the utlisation of vital substrates by direct binding rather than
      inhibiting the metabolising enzymes themselves. Concurrently, there has been an
      increase in the knowledge surrounding the proteins essential to the metabolism of
      Lipid II at and across the cytoplasmic membrane. In this review, we draw these
      elements together and look to future antimicrobial opportunities in this area. 

PMID- 27025639
TI  - Livestock-Associated MRSA: The Impact on Humans.
AB  - During the past 25 years an increase in the prevalence of methicillin-resistant
      Staphylococcus aureus (HA-MRSA) was recorded worldwide. Additionally, MRSA
      infections may occur outside and independent of hospitals, caused by community
      associated MRSA (CA-MRSA). In Germany, we found that at least 10% of these
      sporadic infections are due to livestock-associated MRSA (LA-MRSA), which is
      initially associated with livestock. The majority of these MRSA cases are
      attributed to clonal complex CC398. LA-MRSA CC398 colonizes the animals
      asymptomatically in about half of conventional pig farms. For about 77%-86% of
      humans with occupational exposure to pigs, nasal carriage has been reported; it
      can be lost when exposure is interrupted. Among family members living at the same
      farms, only 4%-5% are colonized. Spread beyond this group of people is less
      frequent. The prevalence of LA-MRSA in livestock seems to be influenced by farm
      size, farming systems, usage of disinfectants, and in-feed zinc. LA-MRSA CC398 is
      able to cause the same kind of infections in humans as S. aureus and MRSA in
      general. It can be introduced to hospitals and cause nosocomial infections such
      as postoperative surgical site infections, ventilator associated pneumonia,
      septicemia, and infections after joint replacement. For this reason, screening
      for MRSA colonization at hospital admittance is recommended for farmers and
      veterinarians with livestock contacts. Intrahospital dissemination, typical for
      HA-MRSA in the absence of sufficient hygiene, has only rarely been observed for
      LA-MRSA to date. The proportion of LA-MRSA among all MRSA from nosocomial
      infections is about 3% across Germany. In geographical areas with a comparatively
      high density of conventional farms, LA-MRSA accounts for up to 10% of MRSA from
      septicemia and 15% of MRSA from wound infections. As known from comparative
      genome analysis, LA-MRSA has evolved from human-adapted methicillin-susceptible
      S. aureus, and the jump to livestock was obviously associated with several
      genetic changes. Reversion of the genetic changes and readaptation to humans
      bears a potential health risk and requires tight surveillance. Although most LA
      MRSA (>80%) is resistant to several antibiotics, there are still sufficient
      treatment options. 

PMID- 27025640
TI  - Focus on the Outer Membrane Factor OprM, the Forgotten Player from Efflux Pumps
      Assemblies.
AB  - Antibiotics have been used extensively during several decades and we are now
      facing the emergence of multidrug resistant strains. It has become a major public
      concern, urging the need to discover new strategies to combat them. Among the
      different ways used by bacteria to resist antibiotics, the active efflux is one
      of the main mechanisms. In Gram-negative bacteria the efflux pumps are comprised
      of three components forming a long edifice crossing the complete cell wall from
      the inside to the outside of the cell. Blocking these pumps would permit the
      restoration of the effectiveness of the current antibiotherapy which is why it is
      important to increase our knowledge on the different proteins involved in these
      complexes. A tremendous number of experiments have been performed on the inner
      membrane protein AcrB from Escherichia coli and, to a lesser extent, the protein
      partners forming the AcrAB-TolC pump, but less information is available
      concerning the efflux pumps from other virulent Gram-negative bacteria. The
      present review will focus on the OprM outer membrane protein from the MexAB-OprM
      pump of Pseudomonas aeruginosa, highlighting similarities and differences compare
      to the archetypal AcrAB-TolC in terms of structure, function, and assembly
      properties. 

PMID- 27025642
TI  - Remote Antimicrobial Stewardship in Community Hospitals.
AB  - Antimicrobial stewardship has become standard practice at university medical
      centers, but the practice is more difficult to implement in remote community
      hospitals that lack infectious diseases trained practitioners. Starting in 2011,
      six community hospitals within the Vidant Health system began an antimicrobial
      stewardship program utilizing pharmacists who reviewed charts remotely from
      Vidant Medical Center. Pharmacists made recommendations within the electronic
      medical record (EMR) to streamline, discontinue, or switch antimicrobial agents.
      Totals of charts reviewed, recommendations made, recommendations accepted, and
      categories of intervention were recorded. Linear regression was utilized to
      measure changes in antimicrobial use over time. For the four larger hospitals,
      recommendations for changes were made in an average of 45 charts per month per
      hospital and physician acceptance of the pharmacists' recommendations varied
      between 83% and 88%. There was no significant decrease in total antimicrobial
      use, but much of the use was outside of the stewardship program's review.
      Quinolone use decreased by more than 50% in two of the four larger hospitals.
      Remote antimicrobial stewardship utilizing an EMR is feasible in community
      hospitals and is generally received favorably by physicians. As more community
      hospitals adopt EMRs, there is an opportunity to expand antimicrobial stewardship
      beyond the academic medical center. 

PMID- 27025641
TI  - Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its
      Relevance to Foodborne Pathogens.
AB  - Concerns have been raised in recent years regarding co-selection for antibiotic
      resistance among bacteria exposed to biocides used as disinfectants, antiseptics
      and preservatives, and to heavy metals (particularly copper and zinc) used as
      growth promoters and therapeutic agents for some livestock species. There is
      indeed experimental and observational evidence that exposure to these non
      antibiotic antimicrobial agents can induce or select for bacterial adaptations
      that result in decreased susceptibility to one or more antibiotics. This may
      occur via cellular mechanisms that are protective across multiple classes of
      antimicrobial agents or by selection of genetic determinants for resistance to
      non-antibiotic agents that are linked to genes for antibiotic resistance. There
      may also be relevant effects of these antimicrobial agents on bacterial community
      structure and via non-specific mechanisms such as mobilization of genetic
      elements or mutagenesis. Notably, some co-selective adaptations have adverse
      effects on fitness in the absence of a continued selective pressure. The present
      review examines the evidence for the significance of these phenomena,
      particularly in respect of bacterial zoonotic agents that commonly occur in
      livestock and that may be transmitted, directly or via the food chain, to human
      populations. 

PMID- 27025643
TI  - Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus
      Persistence to Rifampicin.
AB  - Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis,
      endocarditis, and biofilm infections are difficult to treat because of
      persisters. Despite many efforts in understanding bacterial persistence, the
      mechanisms of persister formation in S. aureus remain elusive. Here, we performed
      a genome-wide screen of a transposon mutant library to study the molecular
      mechanisms involved in persistence of community-acquired S. aureus. Screening of
      the library for mutants defective in persistence or tolerance to rifampicin
      revealed many genes involved in metabolic pathways that are important for
      antibiotic persistence. In particular, the identified mutants belonged to
      metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and
      purine biosynthesis. Five mutants played a role in purine biosynthesis and two
      mutants, purB, an adenylosuccinate lyase, and purM, a
      phosphoribosylaminoimidazole synthetase, were selected for further confirmation.
      Mutants purB and purM showed defective persistence compared to the parental
      strain USA300 in multiple stress conditions including various antibiotics, low
      pH, and heat stress. The defect in persistence was restored by complementation
      with the wildtype purB and purM gene in the respective mutants. These findings
      provide new insights into the mechanisms of persistence in S. aureus and provide
      novel therapeutic targets for developing more effective treatment for persistent
      infections due to S. aureus. 

PMID- 27025644
TI  - Utilizing Monte Carlo Simulations to Optimize Institutional Empiric
      Antipseudomonal Therapy.
AB  - Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections
      with increasing resistance to a limited arsenal of antibiotics. Monte Carlo
      simulation provides antimicrobial stewardship teams with an additional tool to
      guide empiric therapy. We modeled empiric therapies with antipseudomonal beta
      lactam antibiotic regimens to determine which were most likely to achieve
      probability of target attainment (PTA) of >=90%. Microbiological data for P.
      aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and
      prolonged infusion were aztreonam, cefepime, meropenem, and
      piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from
      institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters
      from previously published studies, a 10,000-subject Monte Carlo simulation was
      performed for each regimen to determine PTA. MICs from 272 isolates were included
      in this analysis. No intermittent infusion regimens achieved PTA >=90%. Prolonged
      infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg
      Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of
      piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA
      >=90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of beta
      lactam antibiotics as intermittent infusion did not achieve 90% PTA against P.
      aeruginosa isolated at our institution; however, some prolonged infusions were
      able to achieve these targets. 

PMID- 27025645
TI  - Examining the Clinical Effectiveness of Non-Carbapenem beta-Lactams for the
      Treatment of Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae.
AB  - Treatment options for extended-spectrum beta-lactamase-producing
      Enterobacteriaceae are limited. Piperacillin-tazobactam and cefepime represent
      potential alternative treatment options; however, large prospective studies are
      lacking. This review evaluates the current literature regarding use of
      piperacillin-tazobactam and cefepime for the treatment of extended-spectrum beta
      lactamase-producing Enterobacteriaceae. Antimicrobial stewardship programs can
      play a key role in guiding the best practices for the management of these
      challenging infections. 

PMID- 27025646
TI  - Implementation of a Clinical Decision Support Alert for the Management of
      Clostridium difficile Infection.
AB  - Clostridium difficile infections are common in hospitalized patients and can
      result in significant morbidity and mortality. It is imperative to optimize the
      management of C. difficile infections to help minimize disease complications.
      Antimicrobial stewardship techniques including guidelines, order sets and other
      clinical decision support functionalities may be utilized to assist with therapy
      optimization. We implemented a novel alert within our electronic medical record
      to direct providers to the C. difficile order set in order to assist with
      initiating therapy consistent with institutional guideline recommendations. The
      alert succeeded in significantly increasing order set utilization, but guideline
      compliance was unchanged. 

PMID- 27025647
TI  - Transcriptional profiling analysis of Spodoptera litura larvae challenged with
      Vip3Aa toxin and possible involvement of trypsin in the toxin activation.
AB  - Vip proteins, a new group of insecticidal toxins produced by Bacillus
      thuringiensis, are effective against specific pests including Spodoptera litura.
      Here, we report construction of a transcriptome database of S. litura by de novo
      assembly along with detection of the transcriptional response of S. litura larvae
      to Vip3Aa toxin. In total, 56,498 unigenes with an N50 value of 1,853 bp were
      obtained. Results of transcriptome abundance showed that Vip3Aa toxin provoked a
      wide transcriptional response of the S. litura midgut. The differentially
      expressed genes were enriched for immunity-related, metabolic-related and Bt
      related genes. Twenty-nine immunity-related genes, 102 metabolic-related genes
      and 62 Bt-related genes with differential expression were found. On the basis of
      transcriptional profiling analysis, we focus on the functional validation of
      trypsin which potentially participated in the activation of Vip3Aa protoxin.
      Zymogram analysis indicated that the presence of many proteases, including
      trypsin, in S. litura larvae midgut. Results of enzymolysis in vitro of Vip3Aa by
      trypsin, and bioassay and histopathology of the trypsin-digested Vip3Aa toxin
      showed that trypsin was possibly involved in the Vip3Aa activation. This study
      provides a transcriptome foundation for the identification and functional
      validation of the differentially expressed genes in an agricultural important
      pest, S. litura.

PMID- 27025648
TI  - Assessing the Usability of Six Data Entry Mobile Interfaces for Caregivers: A
      Randomized Trial.
AB  - BACKGROUND: There is an increased demand in hospitals for tools, such as
      dedicated mobile device apps, that enable the recording of clinical information
      in an electronic format at the patient's bedside. Although the human-machine
      interface design on mobile devices strongly influences the accuracy and
      effectiveness of data recording, there is still a lack of evidence as to which
      interface design offers the best guarantee for ease of use and quality of
      recording. Therefore, interfaces need to be assessed both for usability and
      reliability because recording errors can seriously impact the overall level of
      quality of the data and affect the care provided. OBJECTIVE: In this randomized
      crossover trial, we formally compared 6 handheld device interfaces for both speed
      of data entry and accuracy of recorded information. Three types of numerical data
      commonly recorded at the patient's bedside were used to evaluate the interfaces.
      METHODS: In total, 150 health care professionals from the University Hospitals of
      Geneva volunteered to record a series of randomly generated data on each of the 6
      interfaces provided on a smartphone. The interfaces were presented in a
      randomized order as part of fully automated data entry scenarios. During the data
      entry process, accuracy and effectiveness were automatically recorded by the
      software. RESULTS: Various types of errors occurred, which ranged from 0.7% for
      the most reliable design to 18.5% for the least reliable one. The length of time
      needed for data recording ranged from 2.81 sec to 14.68 sec, depending on the
      interface. The numeric keyboard interface delivered the best performance for
      pulse data entry with a mean time of 3.08 sec (SD 0.06) and an accuracy of 99.3%.
      CONCLUSIONS: Our study highlights the critical impact the choice of an interface
      can have on the quality of recorded data. Selecting an interface should be driven
      less by the needs of specific end-user groups or the necessity to facilitate the
      developer's task (eg, by opting for default solutions provided by commercial
      platforms) than by the level of speed and accuracy an interface can provide for
      recording information. An important effort must be made to properly validate
      mobile device interfaces intended for use in the clinical setting. In this
      regard, our study identified the numeric keyboard, among the proposed designs, as
      the most accurate interface for entering specific numerical values. This is an
      important step toward providing clearer guidelines on which interface to choose
      for the appropriate use of handheld device interfaces in the health care setting.

PMID- 27025649
TI  - Molecularly resolved label-free sensing of single nucleobase mismatches by
      interfacial LNA probes.
AB  - So far, there has been no report on molecularly resolved discrimination of single
      nucleobase mismatches using surface-confined single stranded locked nucleic acid
      (ssLNA) probes. Herein, it is exemplified using a label-independent force-sensing
      approach that an optimal coverage of 12-mer ssLNA sensor probes formed onto
      gold(111) surface allows recognition of ssDNA targets with twice stronger force
      sensitivity than 12-mer ssDNA sensor probes. The force distributions are
      reproducible and the molecule-by-molecule force measurements are largely in
      agreement with ensemble on-surface melting temperature data. Importantly, the
      molecularly resolved detection is responsive to the presence of single nucleobase
      mismatches in target sequences. Since the labelling steps can be eliminated from
      protocol, and each force-based detection event occurs within milliseconds' time
      scale, the force-sensing assay is potentially capable of rapid detection. The LNA
      probe performance is indicative of versatility in terms of substrate choice - be
      it gold (for basic research and array-based applications) or silicon (for 'lab-on
      a-chip' type devices). The nucleic acid microarray technologies could therefore
      be generally benefited by adopting the LNA films, in place of DNA. Since LNA is
      nuclease-resistant, unlike DNA, and the LNA-based assay is sensitive to single
      nucleobase mismatches, the possibilities for label-free in vitro rapid
      diagnostics based on the LNA probes may be explored.

PMID- 27025650
TI  - Nascent RNA length dictates opposing effects of NusA on antitermination.
AB  - The NusA protein is a universally conserved bacterial transcription elongation
      factor that binds RNA polymerase (RNAP). When functioning independently, NusA
      enhances intrinsic termination. Paradoxically, NusA stimulates the function of
      the N and Q antiterminator proteins of bacteriophage lambda. The mechanistic
      basis for NusA's functional plasticity is poorly understood. Here we uncover an
      effect of nascent RNA length on the ability of NusA to collaborate with Q.
      Ordinarily, Q engages RNAP during early elongation when it is paused at a
      specific site just downstream of the phage late-gene promoter. NusA facilitates
      this engagement process and both proteins remain associated with the
      transcription elongation complex (TEC) as it escapes the pause and transcribes
      the late genes. We show that the lambda-related phage 82 Q protein (82Q) can also
      engage RNAP that is paused at a promoter-distal position and thus contains a
      nascent RNA longer than that associated with the natively positioned TEC.
      However, the effect of NusA in this context is antagonistic rather than
      stimulatory. Moreover, cleaving the long RNA associated with the promoter-distal
      TEC restores NusA's stimulatory effect. Our findings reveal a critical role for
      nascent RNA in modulating NusA's effect on 82Q-mediated antitermination, with
      implications for understanding NusA's functional plasticity.

PMID- 27025651
TI  - MiR-26 down-regulates TNF-alpha/NF-kappaB signalling and IL-6 expression by
      silencing HMGA1 and MALT1.
AB  - MiR-26 has emerged as a key tumour suppressor in various cancers. Accumulating
      evidence supports that miR-26 regulates inflammation and tumourigenicity largely
      through down-regulating IL-6 production, but the underlying mechanism remains
      obscure. Here, combining a transcriptome-wide approach with manipulation of
      cellular miR-26 levels, we showed that instead of directly targeting IL-6 mRNA
      for gene silencing, miR-26 diminishes IL-6 transcription activated by TNF-alpha
      through silencing NF-kappaB signalling related factors HMGA1 and MALT1. We
      demonstrated that miR-26 extensively dampens the induction of many inflammation
      related cytokine, chemokine and tissue-remodelling genes that are activated via
      NF-kappaB signalling pathway. Knocking down both HMGA1 and MALT1 by RNAi had a
      silencing effect on NF-kappaB-responsive genes similar to that caused by miR-26.
      Moreover, we discovered that poor patient prognosis in human lung adenocarcinoma
      is associated with low miR-26 and high HMGA1 or MALT1 levels and not with levels
      of any of them individually. These new findings not only unravel a novel
      mechanism by which miR-26 dampens IL-6 production transcriptionally but also
      demonstrate a direct role of miR-26 in down-regulating NF-kappaB signalling
      pathway, thereby revealing a more critical and broader role of miR-26 in
      inflammation and cancer than previously realized.

PMID- 27025654
TI  - Stabilization of carbon dioxide (CO2) bubbles in micrometer-diameter aqueous
      droplets and the formation of hollow microparticles.
AB  - We report an approach to stabilize carbon dioxide (CO2) gas bubbles encapsulated
      in micrometer-diameter aqueous drops when water in the aqueous drops is
      evaporated. CO2-in-water-in-oil double emulsion drops are generated using
      microfluidic approaches and evaporation is conducted in the presence of sodium
      dodecyl sulfate (SDS), poly(vinyl alcohol) (PVA) and/or graphene oxide (GO)
      particles dispersed in the aqueous phase of the double emulsion drops. We examine
      the roles of the bubble-to-drop size ratio, PVA and GO concentration in the
      stabilization of CO2 bubbles upon water evaporation and show that thin-shell
      particles with encapsulated CO2 bubbles can be obtained under optimized
      conditions. The developed approach offers a new strategy to study CO2 dissolution
      and stability on the microscale and the synthesis of novel gas-core
      microparticles.

PMID- 27025652
TI  - The amyloid hypothesis of Alzheimer's disease at 25 years.
AB  - Despite continuing debate about the amyloid beta-protein (or Abeta hypothesis,
      new lines of evidence from laboratories and clinics worldwide support the concept
      that an imbalance between production and clearance of Abeta42 and related Abeta
      peptides is a very early, often initiating factor in Alzheimer's disease (AD).
      Confirmation that presenilin is the catalytic site of gamma-secretase has
      provided a linchpin: all dominant mutations causing early-onset AD occur either
      in the substrate (amyloid precursor protein, APP) or the protease (presenilin) of
      the reaction that generates Abeta. Duplication of the wild-type APP gene in
      Down's syndrome leads to Abeta deposits in the teens, followed by microgliosis,
      astrocytosis, and neurofibrillary tangles typical of AD Apolipoprotein E4, which
      predisposes to AD in > 40% of cases, has been found to impair Abeta clearance
      from the brain. Soluble oligomers of Abeta42 isolated from AD patients' brains
      can decrease synapse number, inhibit long-term potentiation, and enhance long
      term synaptic depression in rodent hippocampus, and injecting them into healthy
      rats impairs memory. The human oligomers also induce hyperphosphorylation of tau
      at AD-relevant epitopes and cause neuritic dystrophy in cultured neurons.
      Crossing human APP with human tau transgenic mice enhances tau-positive
      neurotoxicity. In humans, new studies show that low cerebrospinal fluid (CSF)
      Abeta42 and amyloid-PET positivity precede other AD manifestations by many years.
      Most importantly, recent trials of three different Abeta antibodies (solanezumab,
      crenezumab, and aducanumab) have suggested a slowing of cognitive decline in post
      hoc analyses of mild AD subjects. Although many factors contribute to AD
      pathogenesis, Abeta dyshomeostasis has emerged as the most extensively validated
      and compelling therapeutic target.

PMID- 27025655
TI  - Inhibitors of Cancer Stem Cells.
AB  - The cancer stem cell (CSC) theory is current strategy of cancer treatment.
      Cancers follow pathways of cancer stem cell such as Notch, Wnt and Hedgehog can
      be addressed with natural products or synthetic drugs to diminish the chance of
      new tumours. The cancer growth can also be suppressed by aiming the tumourigenic
      stem cells alone, instead of targeting at reducing complete tumour dimension. The
      recurrence of tumours after years of disease-free survival has prompted interest
      in the concept that cancers may have a stem cell basis. Current assumption holds
      that < 5% of the tumour mass may be chemo-resistant and radio-resistant,
      harbouring stem-like properties that impel tumour survival, development, and
      metastasis. There is intense an investigation to interpret CSCs based on self
      renewal and multi-lineage differentiation. Nevertheless, no successful targeted
      therapies have reached the clinic. The ionophore antibiotic salinomycin that
      selectively kills breast CSCs seems to be a promising anticancer drug. Clinical
      trials conducted by the NIH (National Institute of Health) on several synthetic
      drugs demonstrate the current importance of the issue and predict a bright future
      for such molecular weapons against cancer.

PMID- 27025656
TI  - Omega-3 Polyunsaturated Fatty Acids Enhance Cisplatin Efficacy in Gastric Cancer
      Cells by Inducing Apoptosis via ADORA1.
AB  - It has been suggested that administration of the omega-3 polyunsaturated fatty
      acids (omega-3 PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA), can alter the toxicity and/or activity of several anticancer drugs in
      in vitro and in vivo studies. Here, we investigated the ability of omega-3 PUFAs
      to potentiate the antineoplastic activity of cisplatin (CDDP) in gastric cancer
      cells. The increase in CDDP-induced growth inhibition was measured by the IC50
      values obtained when the cells were incubated with CDDP alone or with CDDP plus
      DHA or EPA. DHA and EPA enhanced the growth-inhibition activity of increasing
      concentrations of CDDP. The interactions between CDDP and DHA or EPA at the
      cellular level were assessed through the combination index (CI) method of Chou
      Talalay. The results demonstrated synergism between CDDP and DHA or EPA in MKN45
      cells. Cell cycle analysis showed that the combination treatment increased G0/G1
      phase and S phase arrest, and significantly increased the number of apoptotic
      cells. According to our previous study, omega -3 PUFAs induce apoptosis of
      gastric cells via ADORA1, a subtype of adenosine receptor functionally related to
      cell death. The ADORA1 mRNA and protein expression was higher in the combination
      treatment than in the individual treatments. Notable, when GC cells were
      pretreated with DPCPX, a selective ADORA1 antagonist, the combination treatment
      effect on apoptosis was significantly reduced. Our results suggest that omega-3
      PUFAs enhance the antineoplastic effects of CDDP in gastric cancer cells, and the
      synergistic effect between omega-3 PUFAs and CDDP is partly dependent on
      activating the ADORA1-mediated apoptosis pathway.

PMID- 27025653
TI  - Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe
      affected non-human primates by intracerebral lentiviral gene therapy.
AB  - Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe
      disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by
      arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively.
      Our previous studies established lentiviral gene therapy (GT) as a rapid and
      effective intervention to provide pervasive supply of therapeutic lysosomal
      enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this
      strategy is similarly effective in juvenile non-human primates (NHP). To provide
      proof of principle for tolerability and biological efficacy of the strategy, we
      established a comprehensive study in normal NHP delivering a clinically relevant
      lentiviral vector encoding for the human ARSA transgene. Then, we injected a
      lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus
      macaques, evaluating for the first time the therapeutic potential of lentiviral
      GT in this unique LSD model. We showed favorable safety profile and consistent
      pattern of LV transduction and enzyme biodistribution in the two models,
      supporting the robustness of the proposed GT platform. We documented moderate
      inflammation at the injection sites, mild immune response to vector particles in
      few treated animals, no indication of immune response against transgenic
      products, and no molecular evidence of insertional genotoxicity. Efficient gene
      transfer in neurons, astrocytes, and oligodendrocytes close to the injection
      sites resulted in robust production and extensive spreading of transgenic enzymes
      in the whole CNS and in CSF, leading to supraphysiological ARSA activity in
      normal NHP and close to physiological GALC activity in the Krabbe NHP, in which
      biological efficacy was associated with preliminary indication of therapeutic
      benefit. These results support the rationale for the clinical translation of
      intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other
      neurodegenerative LSD.

PMID- 27025657
TI  - Social media in cancer care: highlights, challenges & opportunities.

PMID- 27025658
TI  - Special issue of the international symposium on reproductive biology and
      comparative endocrinology: ISRBCE2015.

PMID- 27025659
TI  - NICE recommends exercise and not acupuncture for low back pain.

PMID- 27025660
TI  - An infrared-driven flexible pyroelectric generator for non-contact energy
      harvester.
AB  - In recent years, energy harvesting technologies, which can scavenge many kinds of
      energies from our living environment to power micro/nanodevices, have attracted
      increasing attention. However, remote energy transmission, flexibility and
      electric waveform controllability remain the key challenges for wireless power
      supply by an energy harvester. In this paper, we design a new infrared-driven non
      contact pyroelectric generator for harvesting heat energy, which avoids direct
      contact between the pyroelectric generator and heat source and realizes remote
      energy transfer exploiting the photothermal and penetrability of infrared light.
      The output voltage (under the input impedance of 100 MOhm) and short-circuit
      current of the pyroelectric generator consisting of a CNT/PVDF/CNT layer (20 mm *
      5 mm * 100 MUm) can be as large as 1.2 V and 9 nA, respectively, under a 1.45 W
      cm(-2) near-infrared laser (808 nm). We also demonstrate the means by which the
      pyroelectric generator can modulate square waveforms with controllable periods
      through irradiation frequency, which is essential for signal sources and medical
      stimulators. The overshoot of square waveforms are in a range of 9.0%-13.1% with
      a rise time of 120 ms. The prepared pyroelectric generator can light a liquid
      crystal display (LCD) in a vacuum chamber from outside. This work paves the way
      for non-contact energy harvesting for some particular occasions where near-field
      energy control is not available. 

PMID- 27025661
TI  - Characterization and expression of AMP-forming Acetyl-CoA Synthetase from
      Dunaliella tertiolecta and its response to nitrogen starvation stress.
AB  - AMP-forming acetyl-CoA synthetase (ACS) catalyzes the formation of acetyl-CoA.
      Here, a cDNA of ACS from Dunaliella tertiolecta (DtACS) was isolated using RACEs.
      The full-length DtACS cDNA (GenBank: KT692941) is 2,464 bp with a putative ORF of
      2,184 bp, which encodes 727 amino acids with a predicted molecular weight of
      79.72 kDa. DtACS has a close relationship with Chlamydomonas reinhardtii and
      Volvox carteri f. nagariensis. ACSs existing in Bacteria, Archaea and Eukaryota
      share ten conserved motifs (A1-A10) and three signature motifs (I-III) of the
      acyl-adenylate/thioester forming enzyme superfamily. DtACS was expressed in E.
      coli BL21 as Trx-His-tagged fusion protein (~100 kDa) and the enzymatic activity
      was detected. The recombinant DtACS was purified by HisTrap(TM) HP affinity
      chromatography to obtain a specific activity of 52.873 U/mg with a yield of
      56.26%, which approached the specific activity of ACS isolated from other
      eukaryotes. Kinetic analysis indicated that the Km of DtACS was 3.59 mM for
      potassium acetate, and the purified DtACS exhibited a temperature optimum of 37 
      degrees C and a pH optimum of 8.0. In addition, the expression levels of DtACS
      were increased after nitrogen starvation cultivation, indicating that ACS
      activity may be related to the lipid accumulation under nitrogen deficient
      condition.

PMID- 27025662
TI  - Minimal effective dose of povidone-iodine in abdominal surgery Our clinical
      experience.
AB  - The aim of this study is to evaluate the thyroid function tests in order to
      examine whether 10 % of Povidone-Iodine(PI), the medication we applied in 1/5
      ratio diluted with 0.9 %NaCl, joins the systemic circulation during clean
      contaminated, contaminated and dirty operations for solid organ hydatid cysts in
      abdominal area to avoid abscess formation and spreading. 7 men and 6 women were
      included to the present study, prospectively. The mean age was 33.69(+/- 13.49).
      TSH, free T3 (fT3) and free T4 (fT4) hormone levels were measured before the
      operation and at the third day of postoperative period. Amount of used povidone
      iodine for patients was recorded. As a result of statistical analysis applied,
      the preoperative and post operative values were not significantly different
      regarding with the measured hormone levels (preTSH vs postTSH: p= 0.984; prefT3
      vs postfT3: p= 0.101; prefT4 vs postfT4: p=0.146). Thus, it has been shown that
      the dose we used is effective, and it does not enters at all or at quite low
      levels into the systemic circulation. Patients whom this application performed,
      abscess and intestinal adhesions have not been observed in our clinical
      experience. We recommend the use of suggested doses of Povidone-Iodine in the
      presence of intraabdominal perforation and abscess or in cases such as carrying a
      risk of cyst spreading to intraabdominal area in hydatid cysts. KEY WORDS:
      Povidone-iodine, Surgical adhesions, Surgical wound infections, Thyroid function
      tests.

PMID- 27025663
TI  - Cyclic voltammetry as a sensitive method for in situ probing of chemical
      transformations in quantum dots.
AB  - The application of electrochemical methods for the characterization of colloidal
      quantum dots (QDs) attracts considerable attention as these methods may allow for
      monitoring of some crucial parameters, such as energetic levels of conduction and
      valence bands as well as surface traps and ligands under real conditions of
      colloidal solution. In the present work we extend the applications of cyclic
      voltammetry (CV) to in situ monitoring of degradation processes of water-soluble
      CdTe QDs. This degradation occurs under lowering of pH to the values around 5,
      i.e. under conditions relevant to bioimaging applications of these QDs, and is
      accompanied by pronounced changes of their photoluminescence. Observed
      correlations between characteristic features of CV diagrams and the fluorescence
      spectra allowed us to propose mechanisms responsible for evolution of the
      photoluminescence properties as well as degradation pathway of CdTe QDs at low
      pH.

PMID- 27025664
TI  - Evaluation of Home Health Care Devices: Remote Usability Assessment.
AB  - BACKGROUND: An increasing amount of health care is now performed in a home
      setting, away from the hospital. While there is growing anecdotal evidence about
      the difficulty patients and caregivers have using increasingly complex health
      care devices in the home, there has been little systematic scientific study to
      quantify the global nature of home health care device usability in the field.
      Research has tended to focus on a handful of devices, making it difficult to gain
      a broad view of the usability of home-care devices in general. OBJECTIVE: The
      objective of this paper is to describe a remote usability assessment method using
      the System Usability Scale (SUS), and to report on the usability of a broad range
      of health care devices using this metric. METHODS: A total of 271 participants
      selected and rated up to 10 home health care devices of their choice using the
      SUS, which scores usability from 0 (unusable) to 100 (highly usable).
      Participants rated a total of 455 devices in their own home without an
      experimenter present. RESULTS: Usability scores ranged from 98 (oxygen masks) to
      59 (home hormone test kits). An analysis conducted on devices that had at least
      10 ratings showed that the effect of device on SUS scores was significant
      (P<.001), and that the usability of these devices was on the low end when
      compared with other commonly used items in the home, such as microwave ovens and
      telephones. CONCLUSIONS: A large database of usability scores for home health
      care devices collected using this remote methodology would be beneficial for
      physicians, patients, and their caregivers.

PMID- 27025665
TI  - Maximum-likelihood estimation of scatter components algorithm for x-ray coherent
      scatter computed tomography of the breast.
AB  - Coherent scatter computed tomography (CSCT) is a reconstructive x-ray imaging
      technique that yields the spatially resolved coherent-scatter cross section of
      the investigated object revealing structural information of tissue under
      investigation. In the original CSCT proposals the reconstruction of images from
      coherently scattered x-rays is done at each scattering angle separately using
      analytic reconstruction. In this work we develop a maximum likelihood estimation
      of scatter components algorithm (ML-ESCA) that iteratively reconstructs images
      using a few material component basis functions from coherent scatter projection
      data. The proposed algorithm combines the measured scatter data at different
      angles into one reconstruction equation with only a few component images. Also,
      it accounts for data acquisition statistics and physics, modeling effects such as
      polychromatic energy spectrum and detector response function. We test the
      algorithm with simulated projection data obtained with a pencil beam setup using
      a new version of MC-GPU code, a Graphical Processing Unit version of PENELOPE
      Monte Carlo particle transport simulation code, that incorporates an improved
      model of x-ray coherent scattering using experimentally measured molecular
      interference functions. The results obtained for breast imaging phantoms using
      adipose and glandular tissue cross sections show that the new algorithm can
      separate imaging data into basic adipose and water components at radiation doses
      comparable with Breast Computed Tomography. Simulation results also show the
      potential for imaging microcalcifications. Overall, the component images obtained
      with ML-ESCA algorithm have a less noisy appearance than the images obtained with
      the conventional filtered back projection algorithm for each individual
      scattering angle. An optimization study for x-ray energy range selection for
      breast CSCT is also presented. 

PMID- 27025666
TI  - Tracking ocean heat uptake during the surface warming hiatus.
AB  - Ocean heat uptake is observed to penetrate deep into the Atlantic and Southern
      Oceans during the recent hiatus of global warming. Here we show that the deep
      heat penetration in these two basins is not unique to the hiatus but is
      characteristic of anthropogenic warming and merely reflects the depth of the mean
      meridional overturning circulation in the basin. We find, however, that heat
      redistribution in the upper 350 m between the Pacific and Indian Oceans is
      closely tied to the surface warming hiatus. The Indian Ocean shows an anomalous
      warming below 50 m during hiatus events due to an enhanced heat transport by the
      Indonesian throughflow in response to the intensified trade winds in the
      equatorial Pacific. Thus, the Pacific and Indian Oceans are the key regions to
      track ocean heat uptake during the surface warming hiatus.

PMID- 27025667
TI  - Mammography, US, and MRI for Preoperative Prediction of Extensive Intraductal
      Component of Invasive Breast Cancer: Interobserver Variability and Performances.
AB  - BACKGROUND: Interobserver variability and performances of imaging studies for
      predicting an extensive intraductal component (EIC) of invasive breast cancer
      have not been well established. MATERIALS AND METHODS: Two independent readers
      retrospectively reviewed every preoperative mammography, ultrasonography (US),
      and magnetic resonance imaging (MRI) studies of 145 breast cancers in 144
      patients with surgically confirmed EIC status and recorded the EIC presence for
      each study, using our own descriptors referred to in prior articles. Agreement
      and performance of each study for the prediction of an EIC were assessed. The
      reference standard was surgical pathologic findings. RESULTS: Of 145 breast
      cancers, an EIC was present in 49 cancers (33.8%) in 49 patients. Overall
      agreement was perfect on mammography (kappa = 0.944), and substantial in US
      (kappa = 0.691) or in MRI (kappa = 0.627), and moderate to perfect agreement was
      found on most descriptors (kappa = 0.443-0.81), except some US descriptors (kappa
      = 0.23-0.396). The sensitivity of each study showed no significant differences in
      both readers (0.73-0.82). For the specificity, mammography was better than US in
      2 readers (0.69/0.5; P = .001; 0.72/0.6; P = .007, respectively), and MRI better
      than US in 1 reader (0.79/0.5; P = .039). Performances between the readers showed
      no significant differences in each study. CONCLUSION: According to our data,
      mammography, US, and MRI are valid and reproducible methods for the preoperative
      prediction of an EIC of invasive breast cancer. However, US shows low agreement
      on some descriptors and lower performance than mammography or MRI.

PMID- 27025668
TI  - A population of atypical CD56(-)CD16(+) natural killer cells is expanded in PTSD
      and is associated with symptom severity.
AB  - INTRODUCTION: Post-traumatic stress disorder (PTSD) has been associated with
      immune disturbances, including a higher incidence of infections and autoimmune
      diseases as well as a net pro-inflammatory state. Natural killer (NK) cells, a
      key component of the innate immune system, have been less well-studied in PTSD
      despite their importance in immunity. METHODS: We studied two independent samples
      of combat-exposed male war veterans with or without PTSD, the first ("Discovery
      Sample") to generate hypotheses, and the second ("Validation Sample") to
      replicate the findings. The Discovery Sample was comprised of 42 PTSD subjects
      and 42 controls. The Validation Sample was comprised of 25 PTSD subjects and 30
      controls. Participants had fasting, morning blood samples collected for
      examination of the frequency of NK cell subsets, determined by flow cytometry.
      The current and lifetime Clinician Administered PTSD Scale (CAPS) was used to
      assess symptom severity. Statistical analyses were adjusted for age and BMI.
      RESULTS: PTSD subjects compared to controls had (i) a significantly higher
      relative frequency of atypical CD56(-)CD16(+) NK cells in the Discovery Sample
      (p=0.027), which was replicated in the Validation Sample (p=0.004) and the
      combined sample (p<0.001), and (ii) a non-significantly lower relative frequency
      of CD56(bright)CD16(-) NK cells in the two samples (p=0.082; p=0.118), which
      became statistically significant in the combined sample (p=0.020). Further,
      within subjects with PTSD of both samples, the relative frequency of atypical
      CD56(-)CD16(+) NK cells was near significantly positively correlated with
      lifetime PTSD severity (p=0.074). DISCUSSION: This study is the first to
      characterize NK cell subsets in individuals with PTSD. The results suggest that
      combat-exposed men with PTSD exhibit an aberrant profile of NK cells with
      significantly higher frequencies of an atypical population of CD56(-)CD16(+)
      cells and possibly lower frequencies of the functional CD56(bright)CD16(-) NK
      cell subsets. Higher proportions of dysfunctional CD56(-)CD16(+) cells have been
      reported in certain chronic viral infections and in senescent individuals. It is
      possible that this could contribute to immune dysfunctions and prematurely
      senescent phenotypes seen in PTSD.

PMID- 27025670
TI  - Reply.

PMID- 27025669
TI  - Validation of Noninvasive Measures of Left Ventricular Mechanics in Children: A
      Simultaneous Echocardiographic and Conductance Catheterization Study.
AB  - BACKGROUND: The accuracy of echocardiography in evaluating left ventricular
      contractility has not been validated in children. The objective of this study was
      to compare echocardiographic measures of contractility with those derived from
      pressure-volume loop (PVL) analysis in children. METHODS: Patients with
      relatively normal loading conditions undergoing routine left heart
      catheterization were prospectively enrolled. PVLs were obtained via conductance
      catheters. The gold-standard measure of contractility, end-systolic elastance
      (Ees), was obtained via balloon occlusion of one or both vena cavae.
      Echocardiograms were performed immediately after PVL analysis under the same
      anesthetic conditions. Single-beat estimations of echocardiographic Ees were
      calculated using four different methods. These estimates were calculated using a
      combination of noninvasive blood pressure readings, ventricular volumes derived
      from three-dimensional echocardiography, and Doppler time intervals. RESULTS: Of
      24 patients, 18 patients were heart transplant recipients, and six patients had
      small patent ductus arteriosus or small coronary fistulae. The mean age was 9.1
      +/- 5.6 years. The average invasive Ees was 3.04 +/- 1.65 mm Hg/mL. Invasive Ees
      correlated best with echocardiographic Ees by the method of Tanoue (r = 0.85, P <
      .01), with a mean difference of -0.07 mm Hg/mL (95% limits of agreement, -2.0 to
      1.4 mm Hg/mL). CONCLUSIONS: Echocardiographic estimates of Ees correlate well
      with gold-standard measures obtained via conductance catheters in children with
      relatively normal loading conditions. The use of these noninvasive measures in
      accurately assessing left ventricular contractility appears promising and merits
      further study in children.

PMID- 27025671
TI  - Reply.

PMID- 27025672
TI  - Thinking Outside the Box.

PMID- 27025673
TI  - An Unusual Cecal Mass in an Otherwise Healthy Young Woman.

PMID- 27025674
TI  - Reply.

PMID- 27025675
TI  - Hanging Between Life and Death!

PMID- 27025676
TI  - Combination Therapy With Tenofovir and Peginterferon May Not Be Translated Into
      Current Clinical Practice.

PMID- 27025677
TI  - Epigastric Mass in an Infant With First Episode of Nonbilious Vomiting.

PMID- 27025678
TI  - Skin Lesion After Endoscopic Pseudocyst Drainage.

PMID- 27025679
TI  - An Unusual Cause of Cholecystitis.

PMID- 27025680
TI  - Heavy Alcohol Consumption is Associated with Impaired Endothelial Function.
AB  - AIM: Previous studies have reported that moderate alcohol consumption is
      protective against cardiovascular disease, but heavy alcohol consumption
      increases its risk. Endothelial dysfunction is hypothesized to contribute to the
      development of atherosclerosis and cardiovascular disease. However, few
      population-based studies have examined a potential effect of alcohol consumption
      on endothelial function. METHODS: This study included 404 men aged 30-79 years
      who were recruited from residents in 2 communities under the Circulatory Risk in
      Communities Study in 2013 and 2014. We asked the individuals about the frequency
      and volume of alcohol beverages and converted the data into grams of ethanol per
      day. Endothelial function was assessed by brachial artery flow-mediated dilation
      (FMD) measurements during reactive hyperemia. We performed cross-sectional
      analysis of alcohol consumption and %FMD by logistic regression analysis,
      adjusting for age, baseline brachial artery diameter, body mass index, systolic
      blood pressure, low-density lipoprotein cholesterol, HbA1c, smoking,
      antihypertensive medication use, and community. RESULTS: Individuals who drank >=
      46 g/day ethanol had a lower age-adjusted mean %FMD than non-drinkers (p<0.01).
      Compared with non-drinkers, the age-adjusted odds ratios (ORs) (95% confidence
      interval) of low %FMD (<5.3%) for former, light (<23.0 g/day ethanol), moderate
      (23.0-45.9 g/day ethanol), and heavy (>= 46.0 g/day ethanol) drinkers were 1.61
      (0.67-3.89), 0.84 (0.43-1.66), 1.09 (0.52-2.25), and 2.99 (1.56-5.70),
      respectively. The corresponding multivariable-adjusted ORs were 1.76 (0.69-4.50),
      0.86 (0.42-1.76), 0.98 (0.45-2.12), and 2.39 (1.15-4.95), respectively.
      CONCLUSIONS: Heavy alcohol consumption may be an independent risk factor of
      endothelial dysfunction in Japanese men.

PMID- 27025681
TI  - High Levels of Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in
      Acute Stroke: An Age- and Sex-Matched Cross-Sectional Study.
AB  - AIM: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known to
      be a key molecule in the pathogenesis of atherosclerosis. Although high levels of
      serum soluble LOX-1 (sLOX-1) were demonstrated in patients with acute coronary
      syndrome, there are no reports about acute stroke patients. The aim of the
      present study was to evaluate the levels of sLOX-1 in acute stroke patients
      according to different stroke subtypes. METHODS: We enrolled a total of 377
      patients with a stroke (men/women: 251/126; age: 40-79 years), 250 with ischemic
      stroke and 127 with intracerebral hemorrhage (ICH). Patients were admitted to our
      hospital within 3 days after the onset of stroke. As controls, we randomly
      selected age- and sex-matched subjects without a past history of cardiovascular
      disease according to stroke subtype from the community-based cohort of the Suita
      study. Serum LOX-1 levels were compared between stroke patients and healthy
      controls according to stroke subtype. RESULTS: Median values of serum sLOX-1 in
      stroke patients were significantly higher than those in controls (526 vs. 486
      ng/L in ischemic stroke and 720 vs. 513 ng/L in ICH, respectively). Among
      subtypes of ischemic stroke, median sLOX-1 levels in atherothrombotic brain
      infarction (641 ng/L) only were significantly higher than those in controls (496
      ng/L). Ischemic stroke [odds ratio (OR), 3.80; 95% confidence interval (CI), 1.86
      7.74] and ICH (OR, 5.97; 95% CI, 2.13-16.77) were independently associated with
      high levels of sLOX-1 by multivariate logistic regression analysis. CONCLUSIONS:
      Higher levels of sLOX-1 were observed in patients with acute stoke than in
      controls. High levels of sLOX-1 can be useful as biomarker for acute stroke.

PMID- 27025683
TI  - Significance of Genetic Diagnosis of Familial Hypercholesterolemia.

PMID- 27025682
TI  - Phospholipase A2 Receptor Gene Polymorphisms Alter its Functions and Present a
      Genetic Risk of an Increased Intima-Media Thickness of the Carotid Artery.
AB  - AIMS: Phospholipase A2 receptor 1 (PLA2R) has multiple biological functions other
      than functioning as a receptor for secretory PLA2s. Two nonsynonymous
      polymorphisms in the C-type lectin-like domains (CTLD) 1 of PLA2R gene have been
      associated with idiopathic membranous nephropathy. This study examined whether
      the same PLA2R polymorphisms may alter functions of PLA2R in cells expressing the
      variant PLA2R. In addition, the clinical relevance of the experiment was
      examined. METHODS: Two nonsynonymous polymorphisms (T/C at rs3749117 and G/C at
      rs35771982) in CTLD1 of PLA2R gene were completely linked. HEK293 cells
      expressing human wild-type PLA2R (T at rs3749117 and G at rs35771982) or human
      mutant PLA2R that had double mutations (C at rs3749117 and C at rs35771982) were
      constructed. RESULTS: HEK293 cells expressing mutant PLA2R had lower migratory
      and proliferative responses to collagen I compared with cells expressing wild
      type PLA2R. In 580 male patients, PLA2R gene polymorphisms were associated with
      an increase in maximum intima-media thickness (maxIMT) of the carotid artery. The
      multivariate regression model showed that PLA2R gene polymorphisms were a risk
      factor of an increased maxIMT that was independent of conventional risk factors
      (OR=1.93, 95% CI: 1.17-3.19, p<0.01). CONCLUSIONS: The nonsynonymous common
      variants of PLA2R gene altered biological functions in cells expressing variant
      PLA2R. PLA2R gene polymorphisms present a genetic risk of an increased IMT of the
      carotid artery in male. The functional changes in the variant PLA2R may
      potentially be responsible for its association with an increased IMT of the
      carotid artery.

PMID- 27025685
TI  - Electric-field-induced AFE-FE transitions and associated strain/preferred
      orientation in antiferroelectric PLZST.
AB  - Electric-field-induced, antiferroelectric-ferroelectric (AFE-FE) phase
      transitions are common for AFE materials. To date, the strain and preferred
      orientation evolution as well as the role of the intermediate FE state during the
      successive AFE-FE-AFE phase transitions has not been clear. To this end, we have
      herein studied a typical AFE Pb0.97La0.02(Zr0.56Sn0.33Ti0.11)O3 (PLZST) material
      using in-situ neutron diffraction. It is striking that the AFE-FE phase
      transition is not fully reversible: in the electric-field-induced FE state, the
      induced strain exhibits an elliptical distribution, which in turn leads to
      significant preferred orientation in the final AFE state after withdrawal of the
      applied electric-field. The omega-dependent neutron diffraction patterns show
      clear evidence of the induced strain distribution and associated preferred
      orientation arising from the AFE-FE phase transition. The current work also
      provides an explanation for several temperature and electric-field dependent
      dielectric anomalies as well as unrecovered strain change which appear in AFE
      materials after exposure to sufficiently high electric fields. 

PMID- 27025684
TI  - Towards repurposing the yeast peroxisome for compartmentalizing heterologous
      metabolic pathways.
AB  - Compartmentalization of enzymes into organelles is a promising strategy for
      limiting metabolic crosstalk and improving pathway efficiency, but improved tools
      and design rules are needed to make this strategy available to more engineered
      pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a
      sensitive high-throughput assay for peroxisomal cargo import. We identify an
      enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non
      native cargo proteins. Additionally, we perform the first systematic in vivo
      measurements of nonspecific metabolite permeability across the peroxisomal
      membrane using a polymer exclusion assay. Finally, we apply these new insights to
      compartmentalize a two-enzyme pathway in the peroxisome and characterize the
      expression regimes where compartmentalization leads to improved product titre.
      This work builds a foundation for using the peroxisome as a synthetic organelle,
      highlighting both promise and future challenges on the way to realizing this
      goal. 

PMID- 27025686
TI  - A fatty liver leads to a broken heart?

PMID- 27025687
TI  - Reply to "Hepatic venous pressure gradient for preoperative assessment of
      patients with resectable hepatocellular carcinoma: A comment for moving forward".

PMID- 27025688
TI  - Massage therapy decreases pain and perceived fatigue after long-distance Ironman
      triathlon: a randomised trial.
AB  - QUESTION: Can massage therapy reduce pain and perceived fatigue in the quadriceps
      of athletes after a long-distance triathlon race (Ironman)? DESIGN: Randomised,
      controlled trial with concealed allocation, intention-to-treat analysis and
      blinded outcome assessors. PARTICIPANTS: Seventy-four triathlon athletes who
      completed an entire Ironman triathlon race and whose main complaint was pain in
      the anterior portion of the thigh. INTERVENTION: The experimental group received
      massage to the quadriceps, which was aimed at recovery after competition, and the
      control group rested in sitting. OUTCOME MEASURES: The outcomes were pain and
      perceived fatigue, which were reported using a visual analogue scale, and
      pressure pain threshold at three points over the quadriceps muscle, which was
      assessed using digital pressure algometry. RESULTS: The experimental group had
      significantly lower scores than the control group on the visual analogue scale
      for pain (MD -7 mm, 95% CI -13 to -1) and for perceived fatigue (MD -15 mm, 95%
      CI -21 to -9). There were no significant between-group differences for the
      pressure pain threshold at any of the assessment points. CONCLUSION: Massage
      therapy was more effective than no intervention on the post-race recovery from
      pain and perceived fatigue in long-distance triathlon athletes. TRIAL
      REGISTRATION: Brazilian Registry of Clinical Trials, RBR-4n2sxr.

PMID- 27025689
TI  - Development of a Functional Biomarker for Use in Cell-Based Therapy Studies in
      Seropositive Rheumatoid Arthritis.
AB  - Cell-based therapy has potential therapeutic value in autoimmune diseases such as
      rheumatoid arthritis (RA). In RA, reduction of disease activity has been
      associated with improvement in the function of regulatory T cells (Treg) and
      attenuated responses of proinflammatory effector T cells (Teff). Mesenchymal stem
      cells (MSCs) and related multipotent adult progenitor cells (MAPC) have strong
      anti-inflammatory and immunomodulatory properties and may be able to "reset" the
      immune system to a pre-RA state. MAPC are MSC-like cells that are slightly
      earlier in lineage, have greater expansion capacity, and can be used as "off-the
      shelf" therapy. Assessment of cell-based therapy to treat arthritis and related
      diseases is limited by the lack of available biological correlates that can be
      measured early on and indicate treatment response. We set out to develop a
      functional measure that could be used ex vivo as a biomarker of response. We were
      able to demonstrate that MAPC products could inhibit Teff responses from patients
      with active RA and that Treg from RA patients suppressed Teff. This assay used ex
      vivo can be used with MAPC or Treg alone or in combination and reflects the
      overall level of Teff suppression. Use of a novel functional biomarker as an
      exploratory endpoint in trials of cell-based therapy should be of value to detect
      biological outcomes at a point prior to the time that clinical response might be
      observed. SIGNIFICANCE: Therapy with mesenchymal stem cells and related
      multipotent adult progenitor cells is immune modifying in a variety of diseases.
      There is interest in using cell-based therapy in rheumatoid arthritis (RA) to
      induce tolerance and "reset" the immune system to its pre-RA state. In a clinical
      trial, it should be known as soon as possible if there is a chance of response. A
      biomarker has been developed that permits measurement of the effects of cell
      based therapy on effector T cell function.

PMID- 27025690
TI  - Efficacy of CD34+ Stem Cell Therapy in Nonischemic Dilated Cardiomyopathy Is
      Absent in Patients With Diabetes but Preserved in Patients With Insulin
      Resistance.
AB  - We evaluated the association of diabetes and insulin resistance with the response
      to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). A
      total of 45 outpatients with DCM received granulocyte colony-stimulating factor
      for 5 days. CD34(+) cells were then collected by apheresis and injected
      transendocardially. Twelve patients had diabetes mellitus (DM group), 17 had
      insulin resistance (IR group), and 16 displayed normal glucose metabolism (no-IR
      group). After stimulation, we found higher numbers of CD34(+) cells in the IR
      group (94 +/- 73 * 10(6) cells per liter) than in the no-IR group (54 +/- 35 *
      10(6) cells per liter) or DM group (31 +/- 20 * 10(6) cells per liter; p = .005).
      Similarly, apheresis yielded the highest numbers of CD34(+) cells in the IR group
      (IR group, 216 +/- 110 * 10(6) cells; no-IR group, 127 +/- 82 * 10(6) cells; DM
      group, 77 +/- 83 * 10(6) cells; p = .002). Six months after cell therapy, we
      found an increase in left ventricular ejection fraction in the IR group (+5.6% +/
      6.9%) and the no-IR group (+4.4% +/- 7.2%) but not in the DM group (-0.9% +/-
      5.4%; p = .035). The N-terminal pro-brain natriuretic peptide levels decreased in
      the IR and no-IR groups, but not in the DM group (-606 +/- 850 pg/ml; -698 +/-
      1,105 pg/ml; and +238 +/- 963 pg/ml, respectively; p = .034). Transendocardial
      CD34(+) cell therapy appears to be ineffective in DCM patients with diabetes. IR
      was associated with improved CD34(+) stem cell mobilization and a preserved
      clinical response to cell therapy. SIGNIFICANCE: The present study is the first
      clinical study directly evaluating the effects of altered glucose metabolism on
      the efficacy of CD34(+) stem cell therapy in patients with nonischemic dilated
      cardiomyopathy. The results offer critical insights into the physiology of stem
      cell mobilization in heart failure and possibly an explanation for the often
      conflicting results obtained with stem cell therapy for heart failure. These
      results demonstrate that patients with dilated cardiomyopathy and diabetes do not
      benefit from autologous CD34(+) cell therapy. This finding could serve as a
      useful tool when selecting heart failure patients for future clinical studies in
      the field of stem cell therapy.

PMID- 27025691
TI  - Residual beta-Cell Function Predicts Clinical Response After Autologous
      Hematopoietic Stem Cell Transplantation.
AB  - New strategies of autologous hematopoietic stem cell transplantation (auto-HSCT)
      have gained much interest for the treatment of type 1 diabetes mellitus. However,
      assessing the clinical response and residual beta-cell function still has
      limitations. The aim of the study was to select the optimal quantitative index to
      assess pre-existing beta-cell function and to explore its predictive function for
      clinical response after auto-HSCT therapy. In this study, all of the patients who
      had undergone auto-HSCT were clustered into a responder group (Deltabeta-score >
      0) and a nonresponder group (Deltabeta-score <= 0). We compared their
      quantitative metabolic indexes at baseline and performed receiver-operating
      characteristic (ROC) analysis to analyze the correlations between the indexes and
      clinical response. Kaplan-Meier analysis was conducted to compare the cumulative
      response durations in each quartile of the selected indexes. In an average of
      15.13 +/- 6.15 months of follow-up, 44 of 112 patients achieved a clinical
      response. The responder group had lower levels of fasting plasma glucose and
      quantitative insulin sensitivity check index (QUICKI) but higher levels of
      fasting C-peptide, fasting insulin, and homeostasis model assessments for insulin
      resistance (HOMA-IR). ROC analysis showed that HOMA-IR had the largest area under
      the curve (0.756), which was similar to that of QUICKI. Kaplan-Meier analysis
      further confirmed that the third quartile (1.3371-1.7018) of HOMA-IR or the
      second quartile (0.3523-0.3657) of QUICKI was preferential for a prolonged
      response. In conclusion, HOMA-IR and QUICKI could be optimal measurements for
      beta-cell reserves, and they were predictive for the clinical response after auto
      HSCT. SIGNIFICANCE: The beta-score was comprehensive and reliable in evaluating
      clinical response after autologous hematopoietic stem cell transplantation
      (HSCT). The homeostasis model assessments for insulin resistance and the
      quantitative insulin sensitivity check index could serve as precise assessments
      for residual beta-cell function and good predictors of clinical response. They
      might be used to select optimal clinical trial participants or predict the
      clinical response after auto-HSCT.

PMID- 27025692
TI  - Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic
      Differentiation of Amniotic Fluid Stem Cells.
AB  - Amniotic fluid stem (AFS) cells represent a major source of donor cells for
      cartilage repair. Recently, it became clear that mammalian target of rapamycin
      (mTOR) inhibition has beneficial effects on cartilage homeostasis, but the effect
      of mTOR on chondrogenic differentiation is still elusive. Therefore, the
      objectives of this study were to investigate the effects of mammalian target of
      rapamycin complex 1 (mTORC1) modulation on the expression of SOX9 and on its
      downstream targets during chondrogenic differentiation of AFS cells. We performed
      three-dimensional pellet culturing of AFS cells and of in vitro-expanded, human
      derived chondrocytes in the presence of chondrogenic factors. Inhibition of
      mTORC1 by rapamycin or by small interfering RNA-mediated targeting of raptor
      (gene name, RPTOR) led to increased AKT activation, upregulation of hypoxia
      inducible factor (HIF) 2A, and an increase in SOX9, COL2A1, and ACAN abundance.
      Here we show that HIF2A expression is essential for chondrogenic differentiation
      and that AKT activity regulates HIF2A amounts. Importantly, engraftment of AFS
      cells in cell pellets composed of human chondrocytes revealed an advantage of
      raptor knockdown cells compared with control cells in their ability to express
      SOX9. Our results demonstrate that mTORC1 inhibition leads to AKT activation and
      an increase in HIF2A expression. Therefore, we suggest that mTORC1 inhibition is
      a powerful tool for enhancing chondrogenic differentiation of AFS cells and also
      of in vitro-expanded adult chondrocytes before transplantation. SIGNIFICANCE:
      Repair of cartilage defects is still an unresolved issue in regenerative
      medicine. Results of this study showed that inhibition of the mammalian target of
      rapamycin complex 1 (mTORC1) pathway, by rapamycin or by small interfering RNA
      mediated targeting of raptor (gene name, RPTOR), enhanced amniotic fluid stem
      cell differentiation toward a chondrocytic phenotype and increased their
      engrafting efficiency into cartilaginous structures. Moreover, freshly isolated
      and in vitro passaged human chondrocytes also showed redifferentiation upon
      mTORC1 inhibition during culturing. Therefore, this study revealed that rapamycin
      could enable a more efficient clinical use of cell-based therapy approaches to
      treat articular cartilage defects.

PMID- 27025694
TI  - Role of Public-Private Partnerships in Meeting Healthcare Challenges in Africa: A
      Perspective From the Private Sector.

PMID- 27025693
TI  - Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived
      Cardiomyocytes Compatible With Global Distribution of Cells for Clinical
      Applications and Toxicology Testing.
AB  - To fully explore the potential of human pluripotent stem cell-derived
      cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these
      cells are required. Here, we evaluated the feasibility to cold store monolayers
      and aggregates of functional CMs obtained from different PSC lines using a fully
      defined clinical-compatible preservation formulation and investigated the time
      frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two
      dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4 degrees C
      for 3 days without compromising cell viability. However, cell viability decreased
      when the cold storage interval was extended to 7 days. We demonstrated that hPSC
      CMs are more resistant to prolonged hypothermic storage-induced cell injury in
      three-dimensional aggregates than in 2D monolayers, showing high cell recoveries
      (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical
      (ultra)structure, gene and protein expression profile, electrophysiological
      profiles, and drug responsiveness. SIGNIFICANCE: The applicability of human
      pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is
      highly dependent on the development of efficient methods for worldwide shipment
      of these cells. This study established effective clinically compatible strategies
      for cold (4 degrees C) storage of hPSC-CMs cultured as two-dimensional (2D)
      monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers
      of hPSC-CMs was found to be dependent on the time of storage, and 3D cell
      aggregates were more resistant to prolonged cold storage than 2D monolayers. Of
      note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM
      ultrastructure, phenotype, or function. This study provides important insights
      into the cold preservation of PSC-CMs that could be valuable in improving global
      commercial distribution of hPSC-CMs.

PMID- 27025695
TI  - Role of Public-Private Partnerships in Meeting Healthcare Challenges in Africa: A
      Perspective From the Public Sector.

PMID- 27025696
TI  - Importance of Public-Private Partnerships: Strengthening Laboratory Medicine
      Systems and Clinical Practice in Africa.
AB  - After the launch of the US President's Emergency Plan for AIDS Relief in 2003, it
      became evident that inadequate laboratory systems and services would severely
      limit the scale-up of human immunodeficiency virus infection prevention, care,
      and treatment programs. Thus, the Office of the US Global AIDS Coordinator,
      Centers for Disease Control and Prevention, and Becton, Dickinson and Company
      developed a public-private partnership (PPP). Between October 2007 and July 2012,
      the PPP combined the competencies of the public and private sectors to boost
      sustainable laboratory systems and develop workforce skills in 4 African
      countries. Key accomplishments of the initiative include measurable and scalable
      outcomes to strengthen national capacities to build technical skills, develop
      sample referral networks, map disease prevalence, support evidence-based health
      programming, and drive continuous quality improvement in laboratories. This
      report details lessons learned from our experience and a series of
      recommendations on how to achieve successful PPPs. 

PMID- 27025697
TI  - Strengthening the Tuberculosis Specimen Referral Network in Uganda: The Role of
      Public-Private Partnerships.
AB  - BACKGROUND: Diagnosis of multidrug-resistant tuberculosis and prompt initiation
      of effective treatment rely on access to rapid and reliable drug-susceptibility
      testing. Efficient specimen transport systems and appropriate training on
      specimen referral contribute to optimal and timely access to tuberculosis
      diagnostic services. METHODS: With support and technical assistance from a public
      private partnership (PPP) between Becton Dickinson and the US President's
      Emergency Plan for AIDS Relief, the Uganda National TB Reference Laboratory
      (NTRL) and National TB and Leprosy Program redesigned the tuberculosis specimen
      transport network and trained healthcare workers with the goal of improving
      multidrug-resistant tuberculosis detection. RESULTS: Between 2008 and 2011, the
      PPP mapped 93% of health facilities and trained 724 healthcare and postal staff
      members covering 72% of districts. Strengthening the tuberculosis specimen
      referral system increased referrals from presumptive multidrug-resistant
      tuberculosis cases by >10-fold, with 94% of specimens reaching the NTRL within
      the established target transport time. CONCLUSIONS: This study demonstrates the
      potential of PPP collaborations with ministries of health to positively influence
      patient care by strengthening laboratory systems through increased access to drug
      susceptibility testing in Uganda. Ongoing efforts to integrate specimen transport
      networks will maximize resources and improve patient management.

PMID- 27025698
TI  - Implementing Laboratory Quality Management Systems in Mozambique: The Becton
      Dickinson-US President's Emergency Plan for AIDS Relief Public-Private
      Partnership Initiative.
AB  - BACKGROUND: Mozambique's ministry of health (MOH) recognized the need to
      establish a national laboratory quality assurance (NLQA) program to improve the
      reliability and accuracy of laboratory testing. The Becton Dickinson-US
      President's Emergency Plan for AIDS Relief Public-Private Partnership (PPP) was
      used to garner MOH commitment and train a cadre of local auditors and managers to
      support sustainability and country ownership of a NLQA program. METHODS: From
      January 2011 to April 2012, the World Health Organization Regional Office for
      Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation
      (SLIPTA) checklist and the Strengthening Laboratory Management Towards
      Accreditation (SLMTA) curriculum were used in 6 MOH laboratories. PPP volunteers
      provided training and mentorship to build the capacity of local auditors and
      program managers to promote institutionalization and sustainability of the
      program within the MOH. RESULTS: SLIPTA was launched in 6 MOH laboratories, and
      final audits demonstrated improvements across the 13 quality system essentials,
      compared with baseline. Training and mentorship of MOH staff by PPP volunteers
      resulted in 18 qualified auditors and 28 managers/quality officers capacitated to
      manage the improvement process in their laboratories. CONCLUSIONS: SLIPTA helps
      laboratories improve the quality and reliability of their service even in the
      absence of full accreditation. Local capacity building ensures sustainability by
      creating country buy-in, reducing costs of audits, and institutionalizing program
      management.

PMID- 27025699
TI  - Findings of Phlebotomy Practices in Kenya in 2010: Need for Action.
AB  - BACKGROUND: Phlebotomy, a commonly performed medical procedure in healthcare, is
      essential for disease diagnosis and patient management. However, poorly performed
      phlebotomy can compromise patient safety, healthcare worker (HCW) safety, and
      specimen quality. We carried out a study between June and July 2010 to assess
      knowledge, quality and safety of phlebotomy before implementation of a public
      private partnership between Becton, Dickinson and Company and the US President's
      Emergency Plan for AIDS Relief. METHODS: This was a cross-sectional observational
      study in 8 healthcare facilities within 4 regions of Kenya. HCWs were observed
      conducting venous and capillary blood collections, and pre- and posttests were
      offered during HCW training. RESULTS: Of 283 blood samples obtained, 194 were
      venous draws conducted by 72 HCWs and 89 were capillary draws performed by 33
      HCWs. Based on 12 preset quality-associated criteria, none of the 194 observed
      phlebotomies met the standard. In total, 91 HCWs were trained in phlebotomy. The
      mean knowledge increase between pre- and posttraining test was 41%, ranging from
      39% to 45% (95% confidence interval, 29.3%-53.5%;P< .001). CONCLUSIONS:
      Inadequate knowledge and imperfect phlebotomy procedures were noted. This formed
      the basis for the safe phlebotomy partnership to address these deficiencies. To
      ensure sustainability, safe phlebotomy practices were integrated into preservice
      training.

PMID- 27025700
TI  - Improved Specimen-Referral System and Increased Access to Quality Laboratory
      Services in Ethiopia: The Role of the Public-Private Partnership.
AB  - BACKGROUND: Nonstandardized specimen-transport logistics, lack of laboratory
      personnel to transport specimens, lack of standard specimen containers, and long
      turnaround time (TAT) hindered access to quality laboratory services. The
      objective of the Becton, Dickinson, and Company (BD)-US President's Emergency
      Plan for AIDS Relief (PEPFAR) Public-Private Partnership (PPP) was to support
      country-specific programs to develop integrated laboratory systems, services, and
      quality improvement strategies, with an emphasis on strengthening the specimen
      referral system (SRS). METHODS: In 2007, through the Centers for Disease Control
      and Prevention (CDC), the Ethiopian Public Health Institute (EPHI) joined with
      the BD-PEPFAR PPP to strengthen laboratory systems. A joint planning and
      assessment committee identified gaps in the SRS for prioritization and
      intervention and piloted the system in Addis Ababa and Amhara Region. RESULTS:
      The PPP established standardized, streamlined specimen logistics, using the
      Ethiopian Postal Service Enterprise to support a laboratory network in which 554
      facilities referred specimens to 160 laboratories. The PPP supported procuring
      400 standard specimen containers and the training of 586 laboratory personnel and
      81 postal workers. The average TAT was reduced from 7 days (range, 2-14 days) to
      2 days (range, 1-3 days) in Addis Ababa and from 10 days (range, 6-21 days) to 5
      days (range, 2-6 days) in Amhara Region. CONCLUSIONS: This study highlights the
      feasibility and untapped potential of PPPs to strengthen laboratory systems. This
      planned and structured approach to improving specimen referral enhanced access to
      quality laboratory services.

PMID- 27025701
TI  - Human Herpes Virus 7 in a Patient with Recurrent Vulvar Ulceration.

PMID- 27025702
TI  - What PASSes for good? Experience-based Swedish and hypothetical British EuroQol 5
      Dimensions preference sets yield markedly different point estimates and patient
      acceptable symptom state cut-off values in chronic arthritis patients on TNF
      blockade.
AB  - OBJECTIVES: Health utilities derived from answers to generic health-related
      quality of life (HRQoL) questionnaires such as the EuroQol 5-Dimensions (EQ-5D)
      are often used in cost-utility analyses (CUAs) of new and expensive treatments.
      Different preference sets (tariffs) used in the computation of utility values and
      quality-adjusted life-years (QALYs) from questionnaire responses (health states)
      yield varying results, potentially affecting decisions of resource allocation.
      The objective of the present study was to compare British (UK), hypothetical, and
      Swedish (SE), experience-based, EQ-5D utilities using data from clinical
      practice. METHOD: UK and SE EQ-5D utilities were computed in an observational
      cohort of patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and
      psoriatic arthritis (PsA) treated with tumour necrosis factor (TNF) blockers,
      comparing point estimates and patient acceptable symptom state (PASS) cut-off
      levels. RESULTS: SE utilities were found to be consistently higher than UK
      utilities, and PASS cut-offs were essentially stable over time. CONCLUSIONS: With
      higher baseline utilities, there may be less room for improvement after an
      intervention and thus less accumulation of QALYs in CUAs applying the SE, as
      opposed to the UK, EQ-5D tariff.

PMID- 27025703
TI  - Optogenetically controlled RAF to characterize BRAF and CRAF protein kinase
      inhibitors.
AB  - Here, we applied optoRAF, an optogenetic tool for light-controlled clustering and
      activation of RAF proteins that mimics the natural occurring RAS-mediated
      dimerization. This versatile tool allows studying the effect on BRAF and CRAF
      homodimer- as well as heterodimer-induced RAF signaling. Vemurafenib and
      dabrafenib are two clinically approved inhibitors for BRAF that efficiently
      suppress the kinase activity of oncogenic BRAF (V600E). However in wild-type BRAF
      expressing cells, BRAF inhibitors can exert paradoxical activation of wild-type
      CRAF. Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF
      and CRAF homo- and heterodimers. Dabrafenib enhanced activity of light-stimulated
      CRAF at low dose and inhibited CRAF signaling at high dose. Moreover, dabrafenib
      increased the protein level of CRAF proteins but not of BRAF proteins. Increased
      CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent
      manner, independent of light activation. 

PMID- 27025705
TI  - Analysis of death in major trauma: value of prompt post mortem computed
      tomography (pmCT) in comparison to office hour autopsy.
AB  - BACKGROUND: To analyze diagnostic accuracy of prompt post mortem Computed
      Tomography (pmCT) in determining causes of death in patients who died during
      trauma room management and to compare the results to gold standard autopsy during
      office hours. METHODS: Multiple injured patients who died during trauma room care
      were enrolled. PmCT was performed immediately followed by autopsy during office
      hours. PmCT and autopsy were analyzed primarily regarding pmCT ability to find
      causes of death and secondarily to define exact causes of death including
      accurate anatomic localizations. For the secondary analysis data was divided in
      group-I with equal results of pmCT and autopsy, group-II with autopsy providing
      superior results and group-III with pmCT providing superior information
      contributing to but not majorly causing death. RESULTS: Seventeen multiple trauma
      patients were enrolled. Since multiple trauma patients were enrolled more
      injuries than patients are provided. Eight patients sustained deadly head
      injuries (47.1%), 11 chest (64.7%), 4 skeletal system (23.5%) injuries and one
      patient drowned (5.8%). Primary analysis revealed in 16/17 patients (94.1%)
      causes of death in accordance with autopsy. Secondary analysis revealed in 9/17
      cases (group-I) good agreement of autopsy and pmCT. In seven cases autopsy
      provided superior results (group-II) whereas in 1 case pmCT found more
      information (group-III). DISCUSSION: The presented work studied the diagnostic
      value of pmCT in defining causes of death in comparison to standard autopsy.
      Primary analysis revealed that in 94.1% of cases pmCT was able to define causes
      of death even if only indirect signs were present. Secondary analysis showed that
      pmCT and autopsy showed equal results regarding causes of death in 52.9%.
      CONCLUSIONS: PmCT is useful in traumatic death allowing for an immediate
      identification of causes of death and providing detailed information on bony
      lesions, brain injuries and gas formations. It is advisable to conduct pmCT
      especially in cases without consent to autopsy to gain information about possible
      causes of death and to rule out possible clinical errors.

PMID- 27025706
TI  - Bias and precision of methods for estimating the difference in restricted mean
      survival time from an individual patient data meta-analysis.
AB  - BACKGROUND: The difference in restricted mean survival time ([Formula: see
      text]), the area between two survival curves up to time horizon [Formula: see
      text], is often used in cost-effectiveness analyses to estimate the treatment
      effect in randomized controlled trials. A challenge in individual patient data
      (IPD) meta-analyses is to account for the trial effect. We aimed at comparing
      different methods to estimate the [Formula: see text] from an IPD meta-analysis.
      METHODS: We compared four methods: the area between Kaplan-Meier curves
      (experimental vs. control arm) ignoring the trial effect (Naive Kaplan-Meier);
      the area between Peto curves computed at quintiles of event times (Peto
      quintile); the weighted average of the areas between either trial-specific Kaplan
      Meier curves (Pooled Kaplan-Meier) or trial-specific exponential curves (Pooled
      Exponential). In a simulation study, we varied the between-trial heterogeneity
      for the baseline hazard and for the treatment effect (possibly correlated), the
      overall treatment effect, the time horizon [Formula: see text], the number of
      trials and of patients, the use of fixed or DerSimonian-Laird random effects
      model, and the proportionality of hazards. We compared the methods in terms of
      bias, empirical and average standard errors. We used IPD from the Meta-Analysis
      of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) and its updated version MAC
      NPC2 for illustration that included respectively 1,975 and 5,028 patients in 11
      and 23 comparisons. RESULTS: The Naive Kaplan-Meier method was unbiased, whereas
      the Pooled Exponential and, to a much lesser extent, the Pooled Kaplan-Meier
      methods showed a bias with non-proportional hazards. The Peto-quintile method
      underestimated the [Formula: see text], except with non-proportional hazards at
      [Formula: see text]= 5 years. In the presence of treatment effect heterogeneity,
      all methods except the Pooled Kaplan-Meier and the Pooled Exponential with
      DerSimonian-Laird random effects underestimated the standard error of the
      [Formula: see text]. Overall, the Pooled Kaplan-Meier method with DerSimonian
      Laird random effects formed the best compromise in terms of bias and variance.
      The [Formula: see text] estimated with the Pooled Kaplan-Meier method was 0.49
      years (95% CI: [-0.06;1.03], p = 0.08) when comparing radiotherapy plus
      chemotherapy vs. radiotherapy alone in the MAC-NPC and 0.59 years (95% CI:
      [0.34;0.84], p < 0.0001) in the MAC-NPC2. CONCLUSIONS: We recommend the Pooled
      Kaplan-Meier method with DerSimonian-Laird random effects to estimate the
      difference in restricted mean survival time from an individual-patient data meta
      analysis.

PMID- 27025707
TI  - The effect of deltoid lengthening on functional outcome for reverse shoulder
      arthroplasty.
AB  - PURPOSE: Reverse shoulder arthroplasty (RSA) is based on the biomechanical
      advantages of lengthening the deltoid while medializing its center of rotation
      (COR). Little evidence exists describing the clinical benefits of these
      biomechanical advantages. The purpose of this study is to assess the relationship
      between deltoid lengthening and medialization of the COR with functional outcomes
      for RSA patients. METHODS: We retrospectively reviewed patients treated with
      primary RSA. Radiographic measurements of deltoid length and COR, assessment of
      forward elevation (FE) and external rotation (ER), and functional outcome scores
      were obtained pre- and postoperatively. Linear regression analyses were performed
      to assess the relationship between these radiographic measurements and changes in
      shoulder functionality. RESULTS: On average, patients improved significantly in
      function and functional outcome scores. Postoperative COR correlated weakly with
      postoperative FE. There were weakly negative correlations between increase in
      acromion to greater tuberosity distance and postoperative FE, and between deltoid
      lengthening and FE improvement. CONCLUSIONS: Our results suggest that deltoid
      lengthening does not correlate with improvements in active FE or ER. These
      findings could indicate that change in deltoid length is less important than
      previously thought. Furthermore, the negative correlations seen could indicate
      that there is over-tensioning of the deltoid in specific cases. Further studies
      are needed to better assess the role of deltoid length and other factors that may
      impact RSA outcomes.

PMID- 27025708
TI  - Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, ameliorates the
      development of liver fibrosis in diabetic Otsuka Long-Evans Tokushima fatty rats.
AB  - BACKGROUND: It is widely understood that insulin resistance (IR) critically
      correlates with the development of liver fibrosis in several types of chronic
      liver injuries. Several experiments have proved that anti-IR treatment can
      alleviate liver fibrosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors
      comprise a new class of antidiabetic agents that inhibit glucose reabsorption in
      the renal proximal tubules, improving IR. The aim of this study was to elucidate
      the effect of an SGLT2 inhibitor on the development of liver fibrosis using obese
      diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and their littermate
      nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. METHODS: Male OLETF and LETO
      rats were intraperitoneally injected with porcine serum twice a week for 12 weeks
      to augment liver fibrogenesis. Different concentrations of ipragliflozin (3 and 6
      mg/kg) were orally administered during the experimental period. Serological and
      histological data were examined at the end of the experimental period. The direct
      effect of ipragliflozin on the proliferation of a human hepatic stellate cell
      (HSC) line, LX-2, was also evaluated in vitro. RESULTS: OLETF rats, but not LETO
      rats, received 12 weeks of porcine serum injection to induce severe fibrosis.
      Treatment with ipragliflozin markedly attenuated the development of liver
      fibrosis and expression of hepatic fibrosis markers, such as alpha smooth muscle
      actin, collagen 1A1, and transforming growth factor beta (TGF-beta), and improved
      IR in a dose-dependent manner in OLETF rats. In contrast, the proliferation of LX
      2 in vitro was not affected, suggesting that ipragliflozin had no significant
      direct effect on the proliferation of HSCs. CONCLUSION: In conclusion, our
      dataset suggests that an SGLT2 inhibitor could alleviate the development of liver
      fibrosis by improving IR in naturally diabetic rats. This may provide the basis
      for creating new therapeutic strategies for chronic liver injuries with IR.

PMID- 27025709
TI  - Understanding Perioperative Transfusion Practices in Gastrointestinal Surgery-a
      Practice Survey of General Surgeons.
AB  - BACKGROUND: Despite guidelines recommending restrictive red blood cell
      transfusion (RBCT) strategies, perioperative transfusion practices still vary
      significantly. To understand the underlying mechanisms that lead to gaps in
      practice, we sought to assess the attitudes of surgeons regarding the
      perioperative management of anemia and use of RBCT in patients having
      gastrointestinal surgery. METHODS: We conducted a self-administered Web-based
      survey of general surgery staff and residents, in a network of eight academic
      institutions at the University of Toronto. We developed a questionnaire using a
      systematic approach of items generation and reduction. We tested face and content
      validity and test-retest reliability. We administered the survey via emails, with
      planned reminders. RESULTS: Total response rate was 48.1 % (62/125). Half (51.0
      %) of respondents stated that they were unlikely to conduct a preoperative anemia
      work-up. About 54.0 % reported ordering preoperative oral iron supplementation
      for anemia. Most respondents indicated using a 70 g/L hemoglobin trigger (92.0 %)
      for transfusion. Factors increasing thresholds above 70 g/L included cardiac
      comorbidity (58.0 %), acute cardiac disease (94.0 %), symptomatic anemia (68.0
      %), and suspected bleeding (58.0 %). With those factors, the transfusion
      threshold often increased above 90 g/L. Respondents perceived RBCTs to increase
      the postoperative morbidity (62 %), but not to impact the mortality (48 %) and
      cancer recurrence (52 %). Institutional protocols (68.0 %), blood conservation
      clinics (44.0 %), and clinical practice guidelines (84.0 %) were believed to
      encourage restrictive use of RBCTs. CONCLUSION: Self-reported perioperative
      transfusion practices for GI surgery are heterogeneous. Few respondents
      investigated preoperative anemia. Stated use of RBCT indications varied from
      recommendations in published guidelines for patients with symptomatic anemia.
      Establishing team consensus and implementing local blood management guidelines
      appear necessary to improve uptake of evidence-based recommendations.

PMID- 27025710
TI  - Population-Based Epidemiology and Mortality of Small Malignant Gastrointestinal
      Stromal Tumors in the USA.
AB  - BACKGROUND AND AIMS: Gastrointestinal stromal tumors (GISTs) have significant
      variability in size and malignant behavior. Our current understanding is limited
      to pathological analyses, autopsy studies, and small case series. The aim of the
      current study is to define the risk factors, incidence, and mortality rates of
      GIST <2 cm in the National Cancer Institute's Surveillance, Epidemiology, and End
      Results database. METHODS: Patients with histologically confirmed malignant GIST
      <2 cm were studied from 2001 to 2011. GIST was defined by GI tumor site codes and
      GIST-specific histology codes. RESULTS: We identified 378 patients with GIST <2
      cm. The average age at diagnosis was 64.0 years with equal sex distribution. The
      most common tumor location was the stomach (62.2 %), followed by the small
      intestine (23.3 %), colon (5.6 %), and rectum (3.4 %). Most patients had
      localized disease (79.4 %), but 11.4 % had regional/distant metastatic disease.
      The annual incidence rate was 4.2 per 10,000,000 (10M). This was the highest
      among Blacks (7.6 per 10M). Among patients with GIST and no additional cancers,
      the 5-year GIST-specific mortality was 12.9 %. Moreover, there was a
      significantly increased 5-year GIST-specific mortality in those patients who had
      regionally advanced (34.0 %) or metastatic GIST (34.3 %), as compared to those
      patients with localized GIST (5.6 %). CONCLUSIONS: This study represents the
      first population-based analysis of malignant GIST <2 cm. While quite rare, these
      tumors have an underappreciated disease-specific mortality. Further studies are
      needed to define the underlying reasons for the identified racial differences, to
      develop novel risk assessment schema for patients with these small tumors, and to
      determine appropriate indications for resection and/or medical therapy.

PMID- 27025711
TI  - Erratum to: Erythema of Rosacea Impairs Health-Related Quality of Life: Results
      of a Meta-analysis.

PMID- 27025712
TI  - Erratum to: Letter from the Editors.

PMID- 27025713
TI  - Erratum to: A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in
      Moderate-to-Severe Plaque Psoriasis.

PMID- 27025714
TI  - Effects of the Ion PGMTM Hi-QTM sequencing chemistry on sequence data quality.
AB  - Massively parallel sequencing (MPS) offers substantial improvements over current
      forensic DNA typing methodologies such as increased resolution, scalability, and
      throughput. The Ion PGMTM is a promising MPS platform for analysis of forensic
      biological evidence. The system employs a sequencing-by-synthesis chemistry on a
      semiconductor chip that measures a pH change due to the release of hydrogen ions
      as nucleotides are incorporated into the growing DNA strands. However,
      implementation of MPS into forensic laboratories requires a robust chemistry. Ion
      Torrent's Hi-QTM Sequencing Chemistry was evaluated to determine if it could
      improve on the quality of the generated sequence data in association with
      selected genetic marker targets. The whole mitochondrial genome and the HID-Ion
      STR 10-plex panel were sequenced on the Ion PGMTM system with the Ion PGMTM
      Sequencing 400 Kit and the Ion PGMTM Hi-QTM Sequencing Kit. Concordance,
      coverage, strand balance, noise, and deletion ratios were assessed in evaluating
      the performance of the Ion PGMTM Hi-QTM Sequencing Kit. The results indicate that
      reliable, accurate data are generated and that sequencing through homopolymeric
      regions can be improved with the use of Ion Torrent's Hi-QTM Sequencing
      Chemistry. Overall, the quality of the generated sequencing data supports the
      potential for use of the Ion PGMTM in forensic genetic laboratories. 

PMID- 27025715
TI  - Contribution of magnetic resonance imaging of the wrist and hand to forensic age
      assessment.
AB  - Forensic age estimation of living individuals is a controversial subject because
      of the imprecision of the available methods which leads to errors. Moreover,
      young persons are exposed to radiation, without diagnostic or therapeutic
      advantage. Recently, non-invasive imaging techniques such as magnetic resonance
      imaging (MRI) have been studied in this context. The aim of this work was to
      study if the analysis of wrist/hand MRI enabled determination of whether a
      subject was 18 years old. Two observers retrospectively analyzed metaphyseal
      epiphyseal fusion of the distal epiphysis of the radius and the ulna and the base
      of the first metacarpus in wrist/hand MRI of living people between 9 and 25 years
      of age. A three-stage scoring system was applied to all epiphyses. Intra- and
      inter-observer variability was excellent. Staging of the distal radial epiphysis
      allowed the subjects to be correctly evaluated with regard to the 18-year-old
      threshold in more than 85 % of cases. Analysis of the radius alone was as good as
      the analysis of the three epiphyses together. Evaluation of the metaphyseal
      epiphyseal fusion of the distal radius in wrist MRI gave good results in forensic
      age estimation. Wrist MRI could meet ethical expectations with regard to the link
      between the benefit and risk of practicing radiologic examination on individuals
      in this context. 

PMID- 27025717
TI  - Copper-Induced Spermatozoa Head Malformation Is Related to Oxidative Damage to
      Testes in CD-1 Mice.
AB  - The molecular mechanism for copper toxicity on spermatozoa quality in mice is not
      well understood. In a 4-week experiment, we challenged 24, 6-week-old male CD-1
      mice with twice-a-week intraperitoneal copper chloride injections and evaluated
      spermatozoa quality, copper levels in the testes, serum testosterone, the
      expression of key antioxidant glutathione peroxidase 5 (GPx5), and the regulated
      androgen receptor (AR) in the mice testes. We compared these outcomes for four
      groups of six mice given doses of 0, 1.25, 2.5, 5.0 mg/kg weight copper chloride
      twice a week for 4 weeks. The mice demonstrated a copper increase spermatozoa
      head malformation in a dose-response manner. However, we observed no changes in
      spermatozoa viability and acrosome integrity in the ratio of mouse body weight to
      testes weight or in the histomorphology of the testes as the average copper level
      increased. Results of our RT-PCR assays, immunohistochemical tests, ELISA, and
      histochemistry analyses indicated that testis GPx5 expression was increased, AR
      expression in the testes was decreased, serum testosterone was decreased, and the
      activity of 3beta-hydroxysteroid dehydrogenase was decreased as the copper dose
      increased. In conclusion, these data show that sublethal exposure to copper
      induces spermatozoa head malformation and influences both mRNA and protein levels
      of GPx5 and AR which is related to copper resides in the testes. 

PMID- 27025716
TI  - Accuracy of scoring of the epiphyses at the knee joint (SKJ) for assessing legal
      adult age of 18 years.
AB  - Important aspects of forensic practice are age estimation and discrimination of
      individuals of unknown age as adults and minors. The developing knee joint was
      recognized as a potential site for age examination in late adolescence. We
      analyzed a sample of anteroposterior x-rays of the knee joints from 446 living
      individuals from Umbria, Italy (234 males and 212 females), aged between 12 and
      26 years. We evaluated the ossification of the distal femoral (DF), proximal
      tibial (PT), and proximal fibular (PF) epiphyses. We took into account possible
      persistence of the epiphyseal scars in the ossified epiphyses by the adopted
      stages of those previously introduced by Cameriere et al. (2012). We also used
      measurements from all three epiphyses to calculate the total score of maturation
      for the knee joint (SKJ). Cohen Kappa coefficients of intrarater agreement for
      staging the DF, PT, and PF epiphyses were 0.839, 0.894, and 0.907, while
      interrater agreement was 0.919, 0.791, and 0.907, respectively. The resulting
      receiver operating characteristic (ROC) curves of SKJ show better discriminatory
      power than those for DF, PT, and PF epiphyses in predicting that the participant,
      either male or female, was an adult or a minor. The areas under the curves for
      SKJ were 0.991 and 0.968 vs. 0.944, 0.962, 0.974 and 0.891, 0.910, 0.918 for
      males and females, respectively. The results of the 2 by 2 contingency tables
      showed that SKJ score of 4 in males and SKJ score of 5 in females were the most
      suitable cut-off value in discriminating between adults and minors. Principally,
      the sensitivity test for males was 0.94, with 95 % confidence interval (95 % CI)
      0.90 to 0.97 and specificity was 0.96 (95 % CI 0.91 to 0.98). The proportion of
      correctly classified individuals was 0.95 (95 % CI 0.91 to 0.97). For females,
      the sensitivity test was 0.89 (95 % CI 0.84 to 0.92) and specificity was 0.92 (95
      % CI 0.87 to 0.96), the proportion of correctly classified individuals was 0.90
      (95 % CI 0.85 to 0.94). These results indicate that the SKJ method may give
      valuable supporting information in forensic procedures for discriminating
      individuals of legal adult age of 18 years. Further studies should address the
      usefulness of the SKJ method in different populations. 

PMID- 27025718
TI  - Protective Effects of Selenium, Vitamin E, and Purple Carrot Anthocyanins on D
      Galactose-Induced Oxidative Damage in Blood, Liver, Heart and Kidney Rats.
AB  - The present study was performed to investigate the protective effects of selenium
      (Se), vitamin E (Vit E) and anthocyanins from purple carrots and their
      combination against the oxidative stress induced by D-galactose in rats. A total
      of 80 male rats were equally divided into 11 groups, one of which acted as
      control (I) just receiving intraperitoneal injections of physiological saline.
      The remaining ten groups (II-XI) were intraperitoneally injected with D-galactose
      at a dose of 400 mg kg(-1) body weight (BW) per day for 42 consecutive days. Rats
      in groups III-XI were treated with antioxidants via gavage per day as follows:
      group III: Se-methylselenocysteine (SeMSC), IV: Se as sodium selenite (Na2SeO3),
      V: Se-enriched yeast (SeY), VI: Vit E as alpha-tocopherol acetate, VII:
      anthocyanin from purple carrots (APC), VIII: APC + Vit E, IX: SeMSC + APC+ Vit E,
      X: Na2SeO3 + APC + Vit E, XI: SeY + Ant + Vit E. The results showed that the rats
      treated with antioxidants (III-XI) showed significant decreases in the levels of
      malondialdehyde (MDA) and carbonyl protein (PCO) compared with the D-galactose
      treated group (II) in the heart, liver, kidneys, and blood. Moreover, there were
      significant increases in the activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px), glutathione (GSH) concentration, and total
      antioxidant capacity (T-AOC) in the heart, liver, kidneys, and blood of
      antioxidant-treated animals (III-XI) than those in control group (I). In
      addition, the combined treatments of two or three antioxidants showed greater
      antioxidant activities than those of individual treatments, suggesting the
      synergistic antioxidant effects of Se, Vit E, and APC. In conclusion, all the
      antioxidants exhibited protective effects against D-galactose-induced oxidative
      damage in rats, and these antioxidants showed a synergistic effect. 

PMID- 27025719
TI  - Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride
      Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.
AB  - Zinc, an essential micronutrient and biochemical element of the human body, plays
      structural, catalytic, and regulatory roles in numerous physiological functions.
      In the current study, the effects of a pretraining oral administration of zinc
      chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training
      bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric
      oxide synthase (iNOS) inhibitor (10, 50, and 100 MUM/side), alone and in
      combination, on the spatial memory retention in Morris water maze (MWM) were
      investigated. Animals were trained for 4 days and tested 48 h after completion of
      training. Also, the molecular effects of these compounds on the expression of
      choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of
      the hippocampus and medial septal area (MSA), were evaluated. Behavioral and
      molecular findings of this study showed that a 2-week oral administration of zinc
      chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT
      expression. Immunohistochemical analysis of post-training bilateral intra
      hippocampal infusion of 1400W revealed a significant increase in ChAT
      immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion
      of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced
      spatial memory impairment in MWM and significantly increased ChAT expression in
      comparison with zinc chloride-treated animals. Taken together, these results
      emphasize the role of selective iNOS inhibitors in reversing zinc chloride
      induced spatial memory deficits via modulation of cholinergic marker expression. 

PMID- 27025720
TI  - Selenium Deficiency Influences the Expression of Selenoproteins and Inflammatory
      Cytokines in Chicken Aorta Vessels.
AB  - Selenium deficiency is known to cause cardiovascular diseases. However, the role
      of Se deficiency in causing oxidative damage and inflammation injury to the aorta
      vessels of chickens is not well known. In the present study, 180 1-day-old
      chickens were randomly divided into two groups, a low-Se group (L group) and a
      control-Se group (C group). The messenger RNA (mRNA) levels of 25 selenoproteins,
      the mRNA and protein expression levels of inflammatory cytokines (including NF
      kappaB, TNF-alpha, COX-2, and PTGES), and the antioxidant levels in chicken aorta
      vessels were examined. The results showed that the mRNA levels of 25
      selenoproteins and the activity of Gpx were decreased, while the mRNA and protein
      expression levels of inflammatory cytokines and the MDA content were increased by
      Se deficiency in chicken aorta vessels. The data from the present study indicated
      that Se deficiency decreases the expression of selenoproteins, reduces
      antioxidant function, and increases the expression of inflammatory factors in
      chicken aorta vessels. 

PMID- 27025721
TI  - Role of Zinc Supplementation in Testicular and Epididymal Damages in Diabetic
      Rat: Involvement of Nrf2, SOD1, and GPX5.
AB  - Zinc (Zn) is one of the most important trace elements required for several
      biological processes. Diabetes negatively affects many organs, and diabetic
      patients are often hypozincemic. The present study aims to investigate the role
      of Zn supplementation in the testes, epididymis, and sperms of streptozotocin
      (STZ)-induced diabetic rat. Serum, testicular, and sperm Zn contents were found
      to be altered in diabetic rat. Biochemical, histopathological, and protein
      expression profiles were determined to decipher the role of Zn in protecting the
      cellular perturbations. Further, histopathological analyses of testes and
      epididymis showed deranged architecture along with other noted abnormalities.
      Diabetic testes showed decreased Nrf2, HO-1, SOD1, PCNA, and Bcl-2 expressions
      whereas increased COX-2, NF-kappaB, MT, IL-6, and p-ERK levels. SOD1 and GPX5
      were decreased in the epididymis of diabetic rat, whereas Zn supplementation
      attenuated these changes. The present results demonstrate the beneficial role of
      Zn supplementation in diabetes-associated testicular alterations of rat. 

PMID- 27025722
TI  - Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human
      Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway.
AB  - Silicon is essential for bone formation. A low-silicon diet leads to bone
      defects, and numerous animal models have demonstrated that silicon
      supplementation increases bone mineral density (BMD) and reduces bone fragility.
      However, the exact mechanism of this action has not been characterized. In this
      study, we aimed to determine the role of biological silicon in the induction of
      osteoblast differentiation and the possible underlying mechanism. We examined
      whether orthosilicic acid promotes collagen type 1 (COL-1) and osteocalcin
      synthesis through the bone morphogenetic protein-2 (BMP-2)/Smad1/5/runt-related
      transcription factor 2 (RUNX2) signaling pathway by investigating its effect in
      vitro at several concentrations on COL-1 and osteocalcin synthesis in human
      osteosarcoma cell lines (MG-63 and U2-OS). The expression of relevant proteins
      was detected by Western blotting following exposure to noggin, an inhibitor of
      BMP-2. In MG-63 cells, immunofluorescence methods were applied to detect changes
      in the expression of BMP-2, phosphorylated Smad1/5 (P-Smad1/5), and RUNX2.
      Furthermore, rat bone mesenchymal stem cells (BMSCs) were used to determine the
      effect of orthosilicic acid on osteogenic differentiation. Exposure to 10 MUM
      orthosilicic acid markedly increased the expression of BMP-2, P-Smad1/5, RUNX2,
      COL-1, and osteocalcin in osteosarcoma cell lines. Enhanced ALP activity and the
      formation of mineralized nodules were also observed under these conditions.
      Furthermore, preconditioning with noggin inhibited the silicon-induced
      upregulation of P-Smad1/5, RUNX2, and COL-1 expression. In conclusion, the BMP
      2/Smad1/5/RUNX2 signaling pathway participates in the silicon-mediated induction
      of COL-1 and osteocalcin synthesis, and orthosilicic acid promotes the osteogenic
      differentiation of rat BMSCs. 

PMID- 27025723
TI  - Effects of acidic water, aluminum, and manganese on testicular steroidogenesis in
      Astyanax altiparanae.
AB  - Metals can influence the gonadal steroidogenesis and endocrine systems of fish,
      thereby affecting their reproduction. The effects of aluminum and manganese in
      acidic water were investigated on steroidogenesis in sexually mature male
      Astyanax altiparanae. Whether mature male fish recover from the effects of metals
      in metal-free water was also assessed. The fish were exposed to 0.5 mg L(-1) of
      isolated or combined aluminum and manganese in acidic pH (5.5) to keep the metals
      bioavailable. The fish underwent 96 h of acute exposure, and samples were taken
      24 and 96 h after the beginning of the experiment. The fish were then maintained
      in metal-free water for 96 h. Plasma levels of testosterone, 11-ketotestosterone,
      17beta-estradiol, and cortisol were measured. Acidic water increased the plasma
      concentration of testosterone and 11-ketotestosterone. Aluminum increased the
      testosterone levels after 96 h of exposure. Manganese increased the 17beta
      estradiol levels after 24 h of exposure and maintained at high levels until the
      end of the experiment. With the exception of acidic pH, which increased cortisol
      levels after 24 h of exposure, no changes were observed in this corticosteroid
      during the acute experiment. Aluminum and manganese together also altered steroid
      levels but without a standard variation. The fish recovered from the effects of
      most exposure conditions after 96 h in metal-free water. A. altiparanae could use
      reproductive tactics to trigger changes in testicular steroidogenesis by
      accelerating spermatogenesis and spermiogenesis, which may interfere with their
      reproductive dynamics. 

PMID- 27025724
TI  - Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis,
      pharyngitis, and adenitis) syndrome.
AB  - Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a
      childhood febrile syndrome of unknown origin that is often cured with
      tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils
      removed from PFAPA patients with those of controls. We used next-generation
      sequencing technology to investigate the bacterial microbiota of the tonsils of
      30 PFAPA patients and 24 controls. We found significant differences in the
      presence and relative abundance of many bacteria between PFAPA cases and
      controls. For example, cyanobacteria, potential producers of microcystins and
      other toxins, were more common in the case samples (14/30, 47 %) than in the
      controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria
      was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01).
      Streptococci were present in all samples in both groups, but their mean relative
      abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p =
      0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella,
      Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils
      in both groups. The microbiota of the tonsils removed from PFAPA patients
      differed significantly from those of the controls. Tonsillar microbiota may play
      a role in triggering the inflammatory processes that lead to symptoms of PFAPA. 

PMID- 27025725
TI  - The Master Quorum-Sensing Regulator OpaR is Activated Indirectly by H-NS in
      Vibrio parahaemolyticus.
AB  - AphA and OpaR are the master regulators of quorum sensing in Vibrio
      parahaemolyticus and there is reciprocal negative regulation between AphA and
      OpaR. The histone-like nucleoid structure (H-NS) protein is a global
      transcriptional repressor of horizontally transferred genes, but a few
      prokaryotic genes, for example flagella genes, are stimulated by H-NS. The
      regulation of opaR by H-NS was investigated using the following methods: primer
      extension, LacZ fusion, quantitative RT-PCR, and electrophoretic mobility shift
      assay. One transcription start site located at 74 bp upstream of opaR was
      detected and its activity was induced by H-NS. Therefore, a single H-NS-dependent
      promoter was transcribed for opaR in V. parahaemolyticus. Because the H-NS
      protein could not bind to the upstream region of opaR and H-NS does not regulate
      aphA, indirect activation of the transcription of opaR by H-NS cannot be mediated
      by the AphA repressor. 

PMID- 27025726
TI  - Effect of Lactobacillus Strains on Intestinal Microflora and Mucosa Immunity in
      Escherichia coli O157:H7-Induced Diarrhea in Mice.
AB  - This study investigated the effects of KLDS 1.8701 and AD1 administrations by
      gavage on intestinal microflora and mucosal immunity in diarrhea mice infected by
      Escherichia coli O157:H7 compared to normal mice. The levels of E. coli,
      Enterobacteria, and Enterococcus decreased significantly (P < 0.05), while viable
      counts of Lactobacilli and Bifidobacterium increased in diarrhea mice. Moreover,
      KLDS 1.8701 and AD1 improved secretion of secretory immunoglobulin A and enhanced
      the levels of interferon-gamma and interleukin. Results indicate that KLDS 1.8701
      and AD1 could effectively alleviate diarrhea in mice via modulation of intestinal
      microflora and improve the function of immune system. The study on the effect of
      KLDS1.8701 and AD1 supplementation in human flora-associated animal models was
      recommended. 

PMID- 27025727
TI  - Barriers and enablers to the delivery of psychological care in the management of
      patients with type 2 diabetes mellitus in China: a qualitative study using the
      theoretical domains framework.
AB  - BACKGROUND: China has the largest number of type 2 diabetes mellitus (T2DM) cases
      globally and individuals with T2DM have an increased risk of developing mental
      health disorders and functional problems. Despite guidelines recommending that
      psychological care be delivered in conjunction with standard T2DM care;
      psychological care is not routinely delivered in China. Community Health Centre
      (CHC) doctors play a key role in the management of patients with T2DM in China.
      Understanding the behavioural determinants of CHC doctors in the implementation
      of psychological care recommendations allows for the design of targeted and
      culturally appropriate interventions. As such, this study aimed to examine
      barriers and enablers to the delivery of psychological care to patients with T2DM
      from the perspective of CHC doctors in China. METHODS: Two focus groups were
      conducted with 23 CHC doctors from Shenzhen, China. The discussion guide applied
      the Theoretical Domains Framework (TDF) that examines current practice and
      identifies key barriers and enablers perceived to influence practice. Focus
      groups were conducted with an interpreter, and were digitally recorded and
      transcribed. Two researchers independently coded transcripts into pre-defined
      themes using deductive thematic analysis. RESULTS: Barriers and enablers
      perceived by doctors as being relevant to the delivery of psychological care for
      patients with T2DM were primarily categorised within eight TDF domains. Key
      barriers included: CHC doctors' knowledge and skills; time constraints; and
      absence of financial incentives. Other barriers included: societal perception
      that treating psychological aspects of health is less important than physical
      health; lack of opinion leaders; doctors' intentional disregard of psychological
      care; and doubts regarding the efficacy of psychological care. In contrast,
      perceived enablers included: training of CHC doctors in psychological skills;
      identification of afternoon/evening clinic times when recommendations could be
      implemented; introduction of financial incentives; and the creation of a
      professional role (e.g. diabetes educator), that could implement psychological
      care recommendations to patients with T2DM. CONCLUSIONS: The utilisation of the
      TDF allowed for the comprehensive understanding of barriers and enablers to the
      implementation of psychological care recommendations for patients with T2DM, and
      consequently, has given direction to future interventions strategies aimed at
      improving the implementation of such recommendations.

PMID- 27025728
TI  - Erratum to: Pornography and the Male Sexual Script: An Analysis of Consumption
      and Sexual Relations.

PMID- 27025729
TI  - Spectral Manifestation of Melanized Fungal Infections in Kidney Transplant
      Recipients: Report of Six Cases.
AB  - Chromoblastomycosis and phaeohyphomycosis are melanized fungal infections, which
      affect skin and subcutaneous tissues in immunocompetent and immunosuppressed
      patients, as solid-organ transplant recipients, respectively. In this present
      study, we report six cases of melanized fungal infection in kidney transplant
      recipients. In five cases, culture of tissue specimens identified two cases of
      Exophiala spp. and three cases of Fonsecaea spp. Molecular identification was
      performed in three cases based on sequencing of rDNA (ITS region) that revealed
      the following agents: Exophiala xenobiotica, Exophiala bergeri and Fonsecaea
      monophora. Clinically, they presented verrucous lesion, erythematous-squamous
      plaque, nodules and lymphangitic distribution. Histopathological aspect was
      tuberculous granuloma, with concomitant presence of muriform bodies and hyphae.
      Some patients presented fungal transepithelial elimination. One patient received
      only terbinafine. Three patients underwent surgery, and two of them received
      itraconazole. In these four cases, the infection did not relapse. The other two
      patients were treated only with itraconazole, one of them is still under
      treatment and the other one was lost to follow-up. These patients presented
      clinical and histopathological characteristics ranging from resistant to
      nonresistant forms. 

PMID- 27025731
TI  - Antibiotic Prescribing in Primary Care and Antimicrobial Resistance in Patients
      Admitted to Hospital with Urinary Tract Infection: A Controlled Observational
      Pilot Study.
AB  - There is growing evidence that primary care prescribed antibiotics lead to
      antibiotic resistance in bacteria causing minor infections or being carried by
      asymptomatic adults, but little research to date has investigated links between
      primary care prescribed antibiotics and resistance among more serious infections
      requiring hospital care. Knowledge of these effects is likely to have a major
      influence on public expectations for, and primary care use of, antibiotics. This
      study aimed to assess the feasibility of recruiting symptomatic adult patients
      admitted to hospital with urinary infections and to link primary and secondary
      data information to investigate the relationship between primary care prescribed
      antibiotics and antimicrobial resistance in these patients. A microbiology
      database search of in patients who had submitted a urine sample identified 740
      patients who were potentially eligible to take part in the study. Of these, 262
      patients did not meet the eligibility criteria, mainly due to use of a urinary
      catheter (40%). Two-hundred and forty three patients could not be recruited as
      the nurse was unable to visit the patients prior to discharge, as they were too
      unwell. Eighty patients provided complete information. Results indicate that
      there is evidence that prior antibiotic use is associated with resistant
      infections in hospital patients. A fully powered study, conducted using routinely
      collected data is proposed to fully clarify the precision of the association. 

PMID- 27025730
TI  - Utility of the Biosynthetic Folate Pathway for Targets in Antimicrobial
      Discovery.
AB  - The need for new antimicrobials is great in face of a growing pool of resistant
      pathogenic organisms. This review will address the potential for antimicrobial
      therapy based on polypharmacological activities within the currently utilized
      bacterial biosynthetic folate pathway. The folate metabolic pathway leads to
      synthesis of required precursors for cellular function and contains a critical
      node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and
      eukaryotes. The DHFR enzyme is currently targeted by methotrexate in anti-cancer
      therapies, by trimethoprim for antibacterial uses, and by pyrimethamine for anti
      protozoal applications. An additional anti-folate target is dihyropteroate
      synthase (DHPS), which is unique to prokaryotes as they cannot acquire folate
      through dietary means. It has been demonstrated as a primary target for the
      longest standing antibiotic class, the sulfonamides, which act synergistically
      with DHFR inhibitors. Investigations have revealed most DHPS enzymes possess the
      ability to utilize sulfa drugs metabolically, producing alternate products that
      presumably inhibit downstream enzymes requiring the produced dihydropteroate.
      Recent work has established an off-target effect of sulfonamide antibiotics on a
      eukaryotic enzyme, sepiapterin reductase, causing alterations in neurotransmitter
      synthesis. Given that inhibitors of both DHFR and DHPS are designed to mimic
      their cognate substrate, which contain shared substructures, it is reasonable to
      expect such "off-target" effects. These inhibitors are also likely to interact
      with the enzymatic neighbors in the folate pathway that bind products of the DHFR
      or DHPS enzymes and/or substrates of similar substructure. Computational studies
      designed to assess polypharmacology reiterate these conclusions. This leads to
      hypotheses exploring the vast utility of multiple members of the folate pathway
      for modulating cellular metabolism, and includes an appealing capacity for
      prokaryotic-specific polypharmacology for antimicrobial applications. 

PMID- 27025732
TI  - Role of Old Antibiotics in the Era of Antibiotic Resistance. Highlighted
      Nitrofurantoin for the Treatment of Lower Urinary Tract Infections.
AB  - Bacterial infections caused by antibiotic-resistant isolates have become a major
      health problem in recent years, since they are very difficult to treat, leading
      to an increase in morbidity and mortality. Nitrofurantoin is a broad-spectrum
      bactericidal antibiotic that, through a complex mode of action which is not
      completely understood, affects both Gram-negative and Gram-positive bacteria.
      Nitrofurantoin has been used successfully for a long time for the prophylaxis and
      treatment of acute lower urinary tract infections in adults, children and
      pregnant women, but the increased emergence of antibiotic resistance has made
      nitrofurantoin a suitable candidate for the treatment of infections caused by
      multidrug-resistant pathogens. Here, we review the mechanism of action,
      antimicrobial spectrum, pharmacology and safety profile of nitrofurantoin. We
      also investigate the therapeutic use of nitrofurantoin, including recent data
      which highlight its role in the management of community urinary tract infection,
      especially in cases of multidrug-resistant isolates, in which oral active
      antimicrobials are limited resources nowadays. 

PMID- 27025733
TI  - Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a
      Subsequent Treatment after Initial Therapy Failure.
AB  - Therapy failure of empirical antibiotic treatments prescribed by primary care
      physicians occurs commonly. The effect of such a treatment on the susceptibility
      to second line antimicrobial drugs is unknown. Resistance to amoxicillin was
      rapidly induced or selected in E. coli at concentrations expected in the
      patient's body. Strains with reduced susceptibility outcompeted the wild-type
      whenever antibiotics were present, even in low concentrations that did not affect
      the growth rates of both strains. Exposure of E. coli to amoxicillin caused
      moderate resistance to cefotaxime. The combined evidence suggests that initial
      treatment by amoxicillin has a negative effect on subsequent therapy with beta
      lactam antibiotics. 

PMID- 27025734
TI  - In Vitro Antibiofilm Efficacies of Different Antibiotic Combinations with Zinc
      Sulfate against Pseudomonas aeruginosa Recovered from Hospitalized Patients with
      Urinary Tract Infection.
AB  - Urinary tract infections (UTIs) are a serious healthcare dilemma influencing
      millions of patients every year and represent the second most frequent type of
      body infection. Pseudomonas aeruginosa is a multidrug-resistant pathogen causing
      numerous chronic biofilm-associated infections including urinary tract,
      nosocomial, and medical devices-related infections. In the present study, the
      biofilm of P. aeruginosa CCIN34519, recovered from inpatients with UTIs, was
      established on polystyrene substratum and scanning electron microscopy (SEM) and
      was utilized for visualization of the biofilm. A previously described in vitro
      system for real-time monitoring of biofilm growth/inhibition was utilized to
      assess the antimicrobial effects of ciprofloxacin, levofloxacin, moxifloxacin,
      norfloxacin, ertapenem, ceftriaxone, gentamicin, and tobramycin as single
      antibiotics as well as in combinations with zinc sulfate (2.5 mM) against P.
      aeruginosa CCIN34519 biofilm. Meanwhile, minimum inhibitory concentrations (MICs)
      at 24 h and mutant prevention concentrations (MPCs) at 96 h were determined for
      the aforementioned antibiotics. The real-time monitoring data revealed diverse
      responses of P. aeruginosa CCIN34519 biofilm to the tested antibiotic-zinc
      sulfate combinations with potential synergisms in cases of fluoroquinolones
      (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) and carbapenem
      (ertapenem) as demonstrated by reduced MIC and MPC values. Conversely,
      considerable antagonisms were observed with cephalosporin (ceftriaxone) and
      aminoglycosides (gentamicin, and tobramycin) as shown by substantially increased
      MICs and MPCs values. Further deliberate in vivo investigations for the promising
      synergisms are required to evaluate their therapeutic potentials for treatment of
      UTIs caused by P. aeruginosa biofilms as well as for developing preventive
      strategies. 

PMID- 27025736
TI  - Ureteral Stents and Foley Catheters-Associated Urinary Tract Infections: The Role
      of Coatings and Materials in Infection Prevention.
AB  - Urinary tract infections affect many patients, especially those who are admitted
      to hospital and receive a bladder catheter for drainage. Catheter associated
      urinary tract infections are some of the most common hospital infections and cost
      the health care system billions of dollars. Early removal is one of the mainstays
      of prevention as 100% of catheters become colonized. Patients with ureteral
      stents are also affected by infection and antibiotic therapy alone may not be the
      answer. We will review the current evidence on how to prevent infections of
      urinary biomaterials by using different coatings, new materials, and drug eluting
      technologies to decrease infection rates of ureteral stents and catheters. 

PMID- 27025737
TI  - Uncomplicated Urinary Tract Infections in Women in a Sao Paulo Quaternary Care
      Hospital: Bacterial Spectrum and Susceptibility Patterns.
AB  - Uncomplicated urinary tract infections (UTI) in women are very common. Regular
      analysis of bacterial flora is important to formulate updated guidelines. The
      objective of this study is to determine and compare the microbiology of UTIs and
      their susceptibility patterns in a quaternary care hospital. In a seven-year
      review, the urine culture results of 480 female patients with uncomplicated UTIs
      were analyzed. Patients were divided into three groups according to their
      diagnosis and treatment characteristics: Group 1, cystitis at outpatient basis;
      group 2, cystitis at the Emergency Unit; and group 3, pyelonephritis. Group 1
      included older patients, with a higher incidence of concomitant diabetes mellitus
      and recurrent UTIs. E. coli was the most common pathogen, responsible for 75.1%
      of cases, mainly for pyelonephritis (87.3%). Of the oral antimicrobials tested
      for cystitis, amoxicillin/clavulanate and nitrofurantoin had the highest
      susceptibility profiles (84.4% and 87.3%, respectively). For E. coli only, their
      susceptibility profiles were as high as 90.8% and 97.4%, respectively. For
      pyelonephritis treatment, fluoroquinoles had a susceptibility profile <90%, while
      ceftriaxone and gentamicin had susceptibility >90%. Uncomplicated UTI treatment
      is becoming more challenging because the susceptibility profiles of oral
      antimicrobials are increasingly resistant. In our environment, cystitis can still
      be managed with nitrofurantoin. Uncomplicated pyelonephritis should be managed
      with ceftriaxone or gentamicin. 

PMID- 27025738
TI  - Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for
      Male Patients with Urethritis.
AB  - To clarify the clinical efficacy of a single oral 2 g dose of azithromycin
      extended-release for heterosexual male patients with urethritis, and the current
      antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective
      clinical trial was conducted from 2011-2013. In patients with gonococcal
      urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates
      of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime
      and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively.
      In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45
      of 50). The microbiological eradication rates for the pathogens were 90.9%
      (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4%
      (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The
      main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120).
      The symptom of diarrhea was mostly temporary and resolved spontaneously. The
      conclusion was that the treatment regimen with a single oral 2 g dose of
      azithromycin extended-release would be effective for patients with urethritis.
      However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and
      Mycoplasma genitalium should be carefully monitored because of possible treatment
      failure. 

PMID- 27025739
TI  - Molecular Targets of beta-Lactam-Based Antimicrobials: Beyond the Usual Suspects.
AB  - The common practice in antibacterial drug development has been to rapidly make an
      attempt to find ever-more stable and broad-spectrum variants for a particular
      antibiotic, once a drug resistance for that antibiotic is detected. We are now
      facing bacterial resistance toward our clinically relevant antibiotics of such a
      magnitude that the conversation for antimicrobial drug development ought to
      include effective new antibiotics with alternative mechanisms of action. The
      electrophilic beta-lactam ring is amenable for the inhibition of different enzyme
      classes by a suitable decoration of the core scaffold. Monocyclic beta-lactams
      lacking an ionizable group at the lactam nitrogen exhibit target preferences
      toward bacterial enzymes important for resistance and virulence. The present
      review intends to draw attention to the versatility of the beta-lactams as
      antimicrobials with "unusual" molecular targets. 

PMID- 27025740
TI  - Anti-Adhesion Activity of A2-type Proanthocyanidins (a Cranberry Major Component)
      on Uropathogenic E. coli and P. mirabilis Strains.
AB  - Urinary tract infections (UTIs) are relatively common in women and may be
      classified as uncomplicated or complicated, depending upon the urinary tract
      anatomy and physiology. Acute uncomplicated cystitis (AUC) occurs when urinary
      pathogens from the bowel or vagina colonize the periurethral mucosa and reach the
      bladder. The vast majority of episodes in healthy women involving the same
      bacterial strain that caused the initial infection are thought to be
      reinfections. About 90% of AUC are caused by uropathogenic Escherichia coli
      (UPEC), but Proteus mirabilis also plays an important role. Several studies
      support the importance of cranberry (Vaccinium macrocarpon) proanthocyanidins in
      preventing adhesion of P-fimbriated UPEC to uroepithelial cells. In this study,
      we evaluated the in vitro anti-adhesion activity of A2-linked proanthocyanidins
      from cranberry on a UPEC and Proteus mirabilis strains and their possible
      influence on urease activity of the latter. A significant reduction of UPEC
      adhesion (up to 75%) on the HT1376 cell line was observed vs. control. For the
      strains of P. mirabilis there was also a reduction of adhesion (up to 75%)
      compared to controls, as well as a reduction in motility and urease activity.
      These results suggest that A2-type cranberry proanthocyanidins could aid in
      maintaining urinary tract health. 

PMID- 27025741
TI  - Value of Provoked or Spontaneous Flank Pain in Men with Febrile Urinary Tract
      Infections.
AB  - BACKGROUND: Our objective was to identify the clinical, laboratory and
      radiological characteristics of febrile urinary tract infections (UTI) in men and
      to focus on the value of flank pain in these men managed in an ambulatory care
      system. METHODS: A network was designed to manage men with febrile UTI without
      hospitalization according to an algorithm designed with different specialists.
      The patients' characteristics were prospectively recorded and each patient was
      followed up until completely cured. We artificially divided patients into two
      groups. Group 1: men without flank pain diagnosed as prostatitis and a second
      group (Group 2) of men with flank pain or provoked flank pain more likely to have
      a pyelonephritis. Groups were compared to find arguments to differentiate
      prostatitis to pyelonephritis. RESULTS: 350 men were included in the study, half
      of these men reported urinary symptoms (dysuria, urgency and burning urination).
      The negative predictive values of the nitrite and leukocytes test were poor alone
      or in combination. The renal ultrasound was never informative. None of the
      patients failed to respond to the treatment. No difference was found between
      groups. CONCLUSIONS: Laboratory test results and radiological features had a poor
      predictive value. Men with suspected pyelonephritis did not evolve differently
      from those with suspected prostatitis. Monitoring and treatment of men with
      febrile UTI does not seem to depend on the existence of a pyelonephritis
      suspected after the presence of a lumbar pain. Ambulatory management of febrile
      UTI is feasible and safe, requiring an efficient network for patient's
      surveillance.

PMID- 27025742
TI  - Adult and Pediatric Intra-Institutional Trends of Ciprofloxacin Susceptibility in
      E. coli Positive Urinary Cultures.
AB  - Antimicrobial drug resistance in treatment of urinary tract infection (UTI)
      continues to rise worldwide. To examine contributions of physician prescribing
      patterns to fluoroquinolone (ciprofloxacin, CP) resistance, we examined
      Escherichia coli (E. coli) resistance patterns in urinary cultures. Since CP
      usage is limited in children, we compared CP resistance trends in adults and
      children to those of more commonly used trimethoprim-sulfamethoxazole (TMP-SMX)
      and nitrofurantoin (NF). Our data show that although the general pediatric
      population has lower resistance to ciprofloxacin, resistance levels are rising
      with increased usage. While NF susceptibility is historically stable, TMP-SMX
      resistance is slightly higher in children compared to adults. In both adults and
      children, antimicrobial resistance patterns vary according to clinical practice
      site, with ambulatory urology patients showing the highest resistance. This
      suggests that physician's prescribing patterns contribute to antimicrobial
      resistance. 

PMID- 27025743
TI  - Antimicrobial Stewardship and Urinary Tract Infections.
AB  - Urinary tract infections are the most common bacterial infections encountered in
      ambulatory and long-term care settings in the United States. Urine samples are
      the largest single category of specimens received by most microbiology
      laboratories and many such cultures are collected from patients who have no or
      questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed
      inappropriately in such patients. Antimicrobial use, whether appropriate or
      inappropriate, is associated with the selection for antimicrobial-resistant
      organisms colonizing or infecting the urinary tract. Infections caused by
      antimicrobial-resistant organisms are associated with higher rates of treatment
      failures, prolonged hospitalizations, increased costs and mortality.
      Antimicrobial stewardship consists of avoidance of antimicrobials when
      appropriate and, when antimicrobials are indicated, use of strategies to optimize
      the selection, dosing, route of administration, duration and timing of
      antimicrobial therapy to maximize clinical cure while limiting the unintended
      consequences of antimicrobial use, including toxicity and selection of resistant
      microorganisms. This article reviews successful antimicrobial stewardship
      strategies in the diagnosis and treatment of urinary tract infections. 

PMID- 27025744
TI  - beta-Lactam Antibiotics Renaissance.
AB  - Since the 1940s beta-lactam antibiotics have been used to treat bacterial
      infections. However, emergence and dissemination of beta-lactam resistance has
      reached the point where many marketed beta-lactams no longer are clinically
      effective. The increasing prevalence of multidrug-resistant bacteria and the
      progressive withdrawal of pharmaceutical companies from antibiotic research have
      evoked a strong reaction from health authorities, who have implemented
      initiatives to encourage the discovery of new antibacterials. Despite this gloomy
      scenario, several novel beta-lactam antibiotics and beta-lactamase inhibitors
      have recently progressed into clinical trials, and many more such compounds are
      being investigated. Here we seek to provide highlights of recent developments
      relating to the discovery of novel beta-lactam antibiotics and beta-lactamase
      inhibitors. 

PMID- 27025745
TI  - Preparation and Microbiological Evaluation of Amphiphilic Kanamycin-Lipoamino
      Acid Ion-Pairs.
AB  - Amphiphilic ion-pairs of kanamycin (KAN) were prepared by evaporation of a water
      ethanol co-solution of KAN base and a lipoamino acid bearing a 12-carbon atoms
      alkyl side chain (LAA12), at different molar ratios. Infrared spectroscopy
      confirmed the structure of ion-pairs, while differential scanning calorimetry
      (DSC) and powder X-ray diffractometry (PXRD) studies supported the formation of
      new saline species with a different crystalline structure than the starting
      components. The solubility pattern shown in a range of both aqueous and organic
      solvents confirmed that the ion-pairs possess an amphiphilic character. The LAA12
      counter-ion showed not to improve the antibacterial activity of KAN, suggesting
      that such chemical strategy is not able to favor the penetration of this drug
      inside the bacteria cells. Nevertheless, a slight improving, i.e., a one-fold
      dilution, was observed in E. coli. The present study can also serve as the basis
      for a further evaluation of LAA ion-pairing of antibiotics, as a means to improve
      the loading of hydrophilic drugs into lipid-based nanocarriers. 

PMID- 27025746
TI  - Understanding Antibiotic Use in Minya District, Egypt: Physician and Pharmacist
      Prescribing and the Factors Influencing Their Practices.
AB  - Overuse of antibiotics has contributed to the emergence of antibiotic-resistant
      bacteria globally. In Egypt, patients can purchase antibiotics without a
      prescription, and we hypothesized frequent inappropriate antibiotic prescribing
      and dispensing. We interviewed physicians (n = 236) and pharmacists (n = 483) and
      conducted focus groups in Minya, Egypt, to assess attitudes and practices
      regarding antibiotic prescribing for outpatient acute respiratory infections
      (ARI). Antibiotics were reportedly prescribed most of the time or sometimes for
      colds by 150 (64%) physicians and 326 (81%) pharmacists. The most commonly
      prescribed antibiotics were beta-lactams. Macrolides were the second most
      commonly prescribed for colds and sinusitis. The prescription of more than one
      antibiotic to treat pneumonia was reported by 85% of physicians. Most respondents
      thought antibiotic overuse contributes to resistance and reported "patient self
      medication" as the biggest driver of overuse. Fifty physicians (21%) reported
      that they had prescribed antibiotics unnecessarily, citing patient over-the
      counter access as the reason. Physicians <40 years of age and those who treat
      adults were more likely to prescribe antibiotics for colds. Overall, we found a
      high rate of unwarranted outpatient antibiotic prescribing and dispensing for
      ARIs. Patient access to OTC antibiotics contributes to over-prescribing. National
      guidelines for ARI treatment, provider education and national policy requiring a
      physician's prescription for antibiotics may improve appropriate antibiotic use
      in Egypt. 

PMID- 27025747
TI  - Synthesis, Antibacterial Evaluation and QSAR of alpha-Substituted-N4-Acetamides
      of Ciprofloxacin and Norfloxacin.
AB  - Twenty six alpha-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO)
      and norfloxacin (NOR) were synthesized and assayed for antibacterial activity
      against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and
      Bacillus subtilis. The derivatives were primarily more active against Gram
      positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar =
      2-pyrimidyl) and CD-10 (alpha-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC
      values, 0.4-0.9 MUM, against Staphylococcus aureus than CIPRO, while only
      compound CD-10 exhibited better activity, 0.1 MUM, against Bacillus subtilis than
      CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (alpha-phenyl, Ar
      = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (alpha-phenyl, Ar = 3
      chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 MUM against
      this strain. The NOR derivatives showed lower activity than NOR itself against
      Staphylococcus aureus, although ND-6 (alpha-phenyl, Ar = 2-methoxyphenyl) and ND
      7 (Ar = 3-chlorophenyl) showed MIC values less than 2 MUM. Two NOR derivatives,
      ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were
      comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (alpha
      phenyl, Ar = 3-chlorophenyl) and ND-10 (alpha-phenyl, Ar = 2-pyrimidyl) exhibited
      MIC values less than 1.0 MUM against the same strain. QSAR revealed that while
      polarity is the major contributing factor in the potency against Staphylococcus
      aureus, it is balanced by lipophilicity and electron density around the acetamide
      group. On the other hand, electron density around the introduced acetamide group
      is the major determining factor in the activity against Bacillus subtilis, with a
      lesser and variable effect for lipophilicity. 

PMID- 27025749
TI  - Uncomplicated Urinary Tract Infections and Antibiotic Resistance-Epidemiological
      and Mechanistic Aspects.
AB  - Uncomplicated urinary tract infections are typically monobacterial and are
      predominantly caused by Escherichia coli. Although several effective treatment
      options are available, the rates of antibiotic resistance in urinary isolates of
      E. coli have increased during the last decade. Knowledge of the actual local
      rates of antibiotic resistant pathogens as well as the underlying mechanisms are
      important factors in addition to the geographical location and the health state
      of the patient for choosing the most effective antibiotic treatment. Recommended
      treatment options include trimethoprim alone or in combination with
      sulfamethoxazol, fluoroquinolones, beta-lactams, fosfomycin-trometamol, and
      nitrofurantoin. Three basic mechanisms of resistance to all antibiotics are
      known, i.e., target alteration, reduced drug concentration and inactivation of
      the drug. These mechanisms-alone or in combination-contribute to resistance
      against the different antibiotic classes. With increasing prevalence,
      combinations of resistance mechanisms leading to multiple drug resistant (mdr)
      pathogens are being detected and have been associated with reduced fitness under
      in vitro situations. However, mdr clones among clinical isolates such as E. coli
      sequence type 131 (ST131) have successfully adapted in fitness and growth rate
      and are rapidly spreading as a worldwide predominating clone of extraintestinal
      pathogenic E. coli. 

PMID- 27025748
TI  - Drug Resistance Mechanisms in Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is a serious public health problem worldwide. Its situation is
      worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium
      tuberculosis, the causative agent of the disease. In recent years, even more
      serious forms of drug resistance have been reported. A better knowledge of the
      mechanisms of drug resistance of M. tuberculosis and the relevant molecular
      mechanisms involved will improve the available techniques for rapid drug
      resistance detection and will help to explore new targets for drug activity and
      development. This review article discusses the mechanisms of action of anti
      tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis.

PMID- 27025750
TI  - Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous
      Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia.
AB  - Antibiotics exert several effects on host cells including regulation of immune
      components. Antimicrobial peptides (AMPs), e.g., cathelicidins and defensins
      display multiple functions in innate immunity. In colonic mucosa, cathelicidins
      are induced by butyrate, a bacterial fermentation product. Here, we investigated
      the effect of antibiotics on butyrate-induced expression of cathelicidins and
      beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that
      ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human
      cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL
      37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis.
      Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the
      rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated
      Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced
      transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of
      HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by
      ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of
      histone H3, an epigenetic event provided a possible mechanism of the suppressive
      effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium
      difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert
      immunomodulatory function by down-regulating AMPs and other immune components in
      colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of
      C. difficile, causing antibiotic-associated diarrhea. 

PMID- 27025751
TI  - Urinary Tract Infections.
AB  - Urinary tract infections (UTI) are among the most frequently acquired infections
      in the community, but also in hospitals and other health care institutions,
      causing a huge amount of antibiotic consumption. During the last decade we have
      seen significant changes in the field of urinary tract infections regarding
      causative pathogens and antibiotic treatment calling for an update of current
      trends. The worldwide increase of uropathogens resistant to former first line
      antibiotics, such as cotrimoxazole, fluoroquinolones and cephalosporins, has had
      detrimental consequences not only for treatment but also for prophylaxis of
      infectious complications after urological interventions. A paradigm shift
      concerning asymptomatic bacteriuria has had a great impact on the definition and
      management of UTIs today [1-4]. [...]. 

PMID- 27025752
TI  - Foreign Body Infection Models to Study Host-Pathogen Response and Antimicrobial
      Tolerance of Bacterial Biofilm.
AB  - The number of implanted medical devices is steadily increasing and has become an
      effective intervention improving life quality, but still carries the risk of
      infection. These infections are mainly caused by biofilm-forming staphylococci
      that are difficult to treat due to the decreased susceptibility to both
      antibiotics and host defense mechanisms. To understand the particular
      pathogenesis and treatment tolerance of implant-associated infection (IAI) animal
      models that closely resemble human disease are needed. Applications of the tissue
      cage and catheter abscess foreign body infection models in the mouse will be
      discussed herein. Both models allow the investigation of biofilm and virulence of
      various bacterial species and a comprehensive insight into the host response at
      the same time. They have also been proven to serve as very suitable tools to
      study the anti-adhesive and anti-infective efficacy of different biomaterial
      coatings. The tissue cage model can additionally be used to determine
      pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the
      tissue cage fluid can be aspirated repeatedly without the need to sacrifice the
      animal. Moreover, with the advance in innovative imaging systems in rodents,
      these models may offer new diagnostic measures of infection. In summary, animal
      foreign body infection models are important tools in the development of new
      antimicrobials against IAI and can help to elucidate the complex interactions
      between bacteria, the host immune system, and prosthetic materials. 

PMID- 27025754
TI  - A Novel Organo-Selenium Bandage that Inhibits Biofilm Development in a Wound by
      Gram-Positive and Gram-Negative Wound Pathogens.
AB  - Biofilm formation in wounds is a serious problem which inhibits proper wound
      healing. One possible contributor to biofilm formation in a wound is the bacteria
      growing within the overlying bandage. To test this mechanism, we used bandages
      that contained a coating of organo-selenium that was covalently attached to the
      bandage. We tested the ability of this coating to kill bacteria on the bandage
      and in the underlying tissue. The bandage material was tested with both lab
      strains and clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa
      and Staphylococcus epidermidis. It was found that the organo-selenium coated
      bandage showed inhibition, of biofilm formation on the bandage in vitro (7-8
      logs), with all the different bacteria tested, at selenium concentrations in the
      coating of less than 1.0%. These coatings were found to remain stable for over
      one month in aqueous solution, 15 min in boiling water, and over 6 years at room
      temperature. The bandages were also tested on a mouse wound model where the
      bacteria were injected between the bandage and the wound. Not only did the
      selenium bandage inhibit biofilm formation in the bandage, but it also inhibited
      biofilm formation in the wound tissue. Since selenium does not leave the bandage,
      this would appear to support the idea that a major player in wound biofilm
      formation is bacteria which grows in the overlying bandage. 

PMID- 27025755
TI  - A Point Prevalence Survey of Antibiotic Use in 18 Hospitals in Egypt.
AB  - Inappropriate antibiotic use leads to increased risk of antibiotic resistance and
      other adverse outcomes. The objectives of the study were to determine the
      prevalence and characteristics of antibiotic use in Egyptian hospitals to
      identify opportunities for quality improvement. A point prevalence survey was
      conducted in 18 hospitals in March 2011. A total of 3408 patients were included
      and 59% received at least one antibiotic, with the most significant use among
      persons <12 years and intensive care unit patients (p < 0.05). Third generation
      cephalosporin were the most commonly prescribed antibiotics (28.7% of
      prescriptions). Reasons for antibiotic use included treatment of community-(27%)
      and healthcare-associated infections (11%) and surgical (39%) and medical (23%)
      prophylaxis. Among surgical prophylaxis recipients, only 28% of evaluable cases
      received the first dose within two hours before incision and only 25% of cases
      received surgical prophylaxis for <24 h. The prevalence of antibiotic use in
      Egyptian hospitals was high with obvious targets for antimicrobial stewardship
      activities including provision of antibiotic prescription guidelines and
      optimization of surgical and medical prophylaxis practices. 

PMID- 27025753
TI  - Acquired Class D beta-Lactamases.
AB  - The Class D beta-lactamases have emerged as a prominent resistance mechanism
      against beta-lactam antibiotics that previously had efficacy against infections
      caused by pathogenic bacteria, especially by Acinetobacter baumannii and the
      Enterobacteriaceae. The phenotypic and structural characteristics of these
      enzymes correlate to activities that are classified either as a narrow spectrum,
      an extended spectrum, or a carbapenemase spectrum. We focus on Class D beta
      lactamases that are carried on plasmids and, thus, present particular clinical
      concern. Following a historical perspective, the susceptibility and kinetics
      patterns of the important plasmid-encoded Class D beta-lactamases and the
      mechanisms for mobilization of the chromosomal Class D beta-lactamases are
      discussed. 

PMID- 27025756
TI  - Resistance to Antimicrobial Peptides in Vibrios.
AB  - Vibrios are associated with a broad diversity of hosts that produce antimicrobial
      peptides (AMPs) as part of their defense against microbial infections. In
      particular, vibrios colonize epithelia, which function as protective barriers and
      express AMPs as a first line of chemical defense against pathogens. Recent
      studies have shown they can also colonize phagocytes, key components of the
      animal immune system. Phagocytes infiltrate infected tissues and use AMPs to kill
      the phagocytosed microorganisms intracellularly, or deliver their antimicrobial
      content extracellularly to circumvent tissue infection. We review here the
      mechanisms by which vibrios have evolved the capacity to evade or resist the
      potent antimicrobial defenses of the immune cells or tissues they colonize. Among
      their strategies to resist killing by AMPs, primarily vibrios use membrane
      remodeling mechanisms. In particular, some highly resistant strains substitute
      hexaacylated Lipid A with a diglycine residue to reduce their negative surface
      charge, thereby lowering their electrostatic interactions with cationic AMPs. As
      a response to envelope stress, which can be induced by membrane-active agents
      including AMPs, vibrios also release outer membrane vesicles to create a
      protective membranous shield that traps extracellular AMPs and prevents
      interaction of the peptides with their own membranes. Finally, once AMPs have
      breached the bacterial membrane barriers, vibrios use RND efflux pumps, similar
      to those of other species, to transport AMPs out of their cytoplasmic space. 

PMID- 27025757
TI  - Old and New Glycopeptide Antibiotics: Action and Resistance.
AB  - Glycopeptides are considered antibiotics of last resort for the treatment of life
      threatening infections caused by relevant Gram-positive human pathogens, such as
      Staphylococcus aureus, Enterococcus spp. and Clostridium difficile. The emergence
      of glycopeptide-resistant clinical isolates, first among enterococci and then in
      staphylococci, has prompted research for second generation glycopeptides and a
      flurry of activity aimed at understanding resistance mechanisms and their
      evolution. Glycopeptides are glycosylated non-ribosomal peptides produced by a
      diverse group of soil actinomycetes. They target Gram-positive bacteria by
      binding to the acyl-D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the growing
      peptidoglycan on the outer surface of the cytoplasmatic membrane. Glycopeptide
      resistant organisms avoid such a fate by replacing the D-Ala-D-Ala terminus with
      D-alanyl-D-lactate (D-Ala-D-Lac) or D-alanyl-D-serine (D-Ala-D-Ser), thus
      markedly reducing antibiotic affinity for the cellular target. Resistance has
      manifested itself in enterococci and staphylococci largely through the expression
      of genes (named van) encoding proteins that reprogram cell wall biosynthesis and,
      thus, evade the action of the antibiotic. These resistance mechanisms were most
      likely co-opted from the glycopeptide producing actinomycetes, which use them to
      avoid suicide during antibiotic production, rather than being orchestrated by
      pathogen bacteria upon continued treatment. van-like gene clusters, similar to
      those described in enterococci, were in fact identified in many glycopeptide
      producing actinomycetes, such as Actinoplanes teichomyceticus, which produces
      teicoplanin, and Streptomyces toyocaensis, which produces the A47934
      glycopeptide. In this paper, we describe the natural and semi-synthetic
      glycopeptide antibiotics currently used as last resort drugs for Gram-positive
      infections and compare the van gene-based strategies of glycopeptide resistance
      among the pathogens and the producing actinomycetes. Particular attention is
      given to the strategy of immunity recently described in Nonomuraea sp. ATCC
      39727. Nonomuraea sp. ATCC 39727 is the producer of A40926, which is the natural
      precursor of the second generation semi-synthetic glycopeptide dalbavancin, very
      recently approved for acute bacterial skin and skin structure infections. A
      thorough understanding of glycopeptide immunity in this producing microorganism
      may be particularly relevant to predict and eventually control the evolution of
      resistance that might arise following introduction of dalbavancin and other
      second generation glycopeptides into clinics. 

PMID- 27025758
TI  - Position-Dependent Influence of the Three Trp Residues on the Membrane Activity
      of the Antimicrobial Peptide, Tritrpticin.
AB  - Antimicrobial peptides (AMPs) constitute promising candidates for the development
      of new antibiotics. Among the ever-expanding family of AMPs, tritrpticin has
      strong antimicrobial activity against a broad range of pathogens. This 13-residue
      peptide has an unusual amino acid sequence that is almost symmetrical and
      features three central Trp residues with two Arg residues near each end of the
      peptide. In this work, the role of the three sequential Trp residues in
      tritrpticin was studied in a systematic fashion by making a series of synthetic
      peptides with single-, double- and triple-Trp substitutions to Tyr or Ala. 1H NMR
      and fluorescence spectroscopy demonstrated the ability of all of the tritrpticin
      analog peptides to interact with negatively-charged membranes. Consequently, most
      tritrpticin analogs exhibited the ability to permeabilize synthetic ePC:ePG (egg
      yolk phosphatidylcholine (ePC), egg-yolk phosphatidylglycerol (ePG)) vesicles and
      live Escherichia coli bacteria. The membrane perturbation characteristics were
      highly dependent on the location of the Trp residue substitution, with Trp6 being
      the most important residue and Trp8 the least. The membrane permeabilization
      activity of the peptides in synthetic and biological membranes was directly
      correlated with the antimicrobial potency of the peptides against E. coli. These
      results contribute to the understanding of the role of each of the three Trp
      residues to the antimicrobial activity of tritrpticin. 

PMID- 27025759
TI  - Patient Attitudes and Beliefs and Provider Practices Regarding Antibiotic Use for
      Acute Respiratory Tract Infections in Minya, Egypt.
AB  - The inappropriate use of antibiotics in the community is one of the major causes
      of antimicrobial resistance. This study aimed to explore the physician
      prescribing pattern of antibiotics for acute respiratory infections (ARIs) and to
      explore the knowledge, attitudes, and practices of patients regarding antibiotic
      use for ARIs. The study was conducted in Upper Egypt and used quantitative and
      qualitative research techniques. Eligible patients exiting outpatient clinics
      with ARIs were invited to participate in the study. A qualitative study was
      conducted through 20 focus group discussions. Out of 350 encounters for patients
      with various ARIs, 292 (83%) had been prescribed at least one antibiotic. Factors
      significantly associated with antibiotic prescribing for adults included patient
      preference that an antibiotic be prescribed. For children younger than 18,
      presentation with fever, cough, loss of appetite, and sore throat, along with the
      caregiver's antibiotic preference, were associated with an antibiotic
      prescription. Several misconceptions regarding antibiotic use among community
      members were stated, such as the strong belief of the curing and prophylactic
      power of antibiotics for the common cold. Interventions to promote proper
      antibiotic use for ARIs need to be piloted, targeting both physicians and the
      public. Educational programs for physicians and campaigns to raise public
      awareness regarding proper antibiotic use for ARIs need to be developed. 

PMID- 27025760
TI  - The Role of Cationic Polypeptides in Modulating HIV-1 Infection of the
      Cervicovaginal Mucosa.
AB  - The mucosa and overlying fluid of the female reproductive tract (FRT) are portals
      for the heterosexual transmission of HIV-1. Toward the ongoing development of
      topically applied microbicides and mucosal vaccines against HIV-1, it is evermore
      important to understand how the dynamic FRT mucosa is involved in controlling
      transmission and infection of HIV-1. Cationic peptides and proteins are the
      principal innate immune effector molecules of mucosal surfaces, and interact in a
      combinatorial fashion to modulate HIV-1 infection of the cervix and vagina. While
      cationic peptides and proteins have historically been categorized as
      antimicrobial or have other host-benefitting roles, an increasing number of these
      molecules have been found to augment HIV-1 infection and potentially antagonize
      host defense. Complex environmental factors such as hormonal fluctuations and/or
      bacterial and viral co-infections provide additional challenges to both
      experimentation and interpretation of results. In the context of heterosexual
      transmission of HIV-1, this review explores how various cationic peptides and
      proteins participate in modulating host defense against HIV-1 of the
      cervicovaginal mucosa. 

PMID- 27025761
TI  - Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein
      and low molecular weight dextran independent of blood-brain barrier modulation.
AB  - Conventional methods for therapeutic blood-brain barrier (BBB) disruption
      facilitate drug delivery but are cumbersome to perform. A previous study
      demonstrated that adenosine receptor (AR) stimulation by 5'-N-ethylcarboxamide
      adenosine (NECA) increased the extravasation of intravascular tracers into the
      brain and proposed that AR agonism may be an effective method for therapeutic BBB
      disruption. We attempted to confirm the extravasation of tracers into the brain
      and also investigated tracer extravasation into peripheral organs and tracer
      retention in the blood. We found that NECA not only increased the extravasation
      of intravascular fluorescein and low molecular weight dextran into the brain of
      mice but also increased the concentrations of these tracers in the blood. In
      fact, the brain:blood ratio-normalized BBB permeability for either tracer is
      actually decreased by NECA administration. Elevated blood urea nitrogen levels in
      mice following NECA treatment suggested that renal function impairment was a
      probable cause of tracer retention. Therefore, NECA has almost no effect on the
      extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer
      with little renal clearance. Rather than inducing BBB disruption, our study
      demonstrated that NECA increased tracer extravasation into the brain by
      increasing the concentration gradient of the tracer across the BBB. 

PMID- 27025762
TI  - Misregulation of Gene Expression and Sterility in Interspecies Hybrids: Causal
      Links and Alternative Hypotheses.
AB  - Understanding the origin of species is of interest to biologist in general and
      evolutionary biologist in particular. Hybrid male sterility (HMS) has been a
      focus in studies of speciation because sterility imposes a barrier to free gene
      flow between organisms, thus effectively isolating them as distinct species. In
      this review, I focus on the role of differential gene expression in HMS and
      speciation. Microarray and qPCR assays have established associations between
      misregulation of gene expression and sterility in hybrids between closely related
      species. These studies originally proposed disrupted expression of
      spermatogenesis genes as a causative of sterility. Alternatively, rapid genetic
      divergence of regulatory elements, particularly as they relate to the male sex
      (fast-male evolution), can drive the misregulation of sperm developmental genes
      in the absence of sterility. The use of fertile hybrids (both backcross and F1
      progeny) as controls has lent support to this alternative explanation.
      Differences in gene expression between fertile and sterile hybrids can also be
      influenced by a pattern of faster evolution of the sex chromosome (fast-X
      evolution) than autosomes. In particular, it would be desirable to establish
      whether known X-chromosome sterility factors can act as trans-regulatory drivers
      of genome-wide patterns of misregulation. Genome-wide expression studies coupled
      with assays of proxies of sterility in F1 and BC progeny have identified
      candidate HMS genes but functional assays, and a better phenotypic
      characterization of sterility phenotypes, are needed to rigorously test how these
      genes might contribute to HMS.

PMID- 27025763
TI  - Geographic variation of inpatient care costs at the end of life.
AB  - BACKGROUND: costs incurred at the end of life are a main contributor to
      healthcare expenditure. Urban-rural inequalities in health outcomes have been
      demonstrated. Issues around geographical patterning of the association between
      time-to-death and expenditure remain under-researched. It is unknown whether
      differences in outcomes translate into differences in costs at the end of life.
      METHODS: we used a large representative sample of the Scottish population
      obtained from death records linked to acute inpatient care episodes. We performed
      retrospective analyses of costs and recorded the most frequent reasons for the
      last hospital admission. Using a two-part model, we estimated the probability of
      healthcare utilisation and costs for those patients who incurred positive costs.
      RESULTS: effects of geography on costs were similar across diagnoses. We did not
      observe a clear gradient for costs, which were lower in other urban areas
      compared with large urban areas. Patients from remote and very remote areas
      incurred higher costs than patients from large, urban areas. The main driver of
      increased costs was increased length of stay. CONCLUSIONS: our results provide
      evidence of additional costs associated with remote locations. If length of stay
      and costs are to be reduced, alternative care provision is required in rural
      areas. Lower costs in other urban areas compared with large urban areas may be
      due to urban centres incurring higher costs through case-mix and clinical
      practice. If inequalities are driven by hospital admission, for an end of life
      scenario, care delivered closer to home or home-based care seems intuitively
      attractive and potentially cost-saving.

PMID- 27025764
TI  - Sub-Lethal Effects of Copper on Salmonids: An Avoidance Evaluation Using a Direct
      Test Method.
AB  - Avoidance of copper (Cu) by rainbow trout (Oncorhynchus mykiss) was evaluated
      using a Y-maze exposure system, with data collected over a 1-h exposure period
      using a digital camcorder. In exposures to five measured concentrations of
      dissolved copper (<0.3, 1.2, 9.8, 48.3, and 98.6 ug Cu/L), plus control,
      significant avoidance behavior (p < 0.05) relative to the control was observed at
      >=9.8 ug Cu/L, but not at 1.2 ug Cu/L. The chronic value (i.e., geometric mean of
      these concentrations) was 3.43 ug Cu/L. Estimates of EC50 values for avoidance of
      Cu ranged from 4.81 to 9.15 ug Cu/L over four 15-min time intervals of exposure
      to the metal. Based on water quality characterization of the control/diluent
      water, the U.S. Environmental Protection Agency (USEPA) water hardness- and
      biotic ligand model (BLM)-based chronic criteria for dissolved Cu were 8.03 and
      2.26 ug Cu/L, respectively. This study suggested that enforcement of the BLM
      based criterion would provide a higher level of protection of trout for this
      sensitive response than the hardness-based criterion. 

PMID- 27025765
TI  - Distribution Characteristics, Concentrations, and Sources of Cd and Pb in
      Laoxiawan Channel Sediments from Zhuzhou, China.
AB  - Twenty sediment cores encompassing surface (0-20 cm) and deeper (50-60 cm)
      sediment layers were retrieved from the 3000 m-long Laoxiawan Channel, which
      receives industrial effluents from Zhuzhou City (China). Analytical results
      showed that cadmium (Cd) concentrations ranged between 115.7-1126.7 and 108.8
      2059.3 mg/kg while lead (Pb) values ranged between 234-3000 and 145-4292 mg/kg in
      the surface and bottom sediments, respectively. The results also indicated that
      high levels of Cd and Pb were present in the vicinity of the channel mouth and
      confluence area. Indices for potential ecological risk and geo-accumulation were
      used to evaluate the environmental effects and intensity of heavy metal pollution
      over time. High concentrations of Cd and Pb in the bottom sediments of Laoxiawan
      Channel were mainly associated with wastewater discharge (10(6) m(3)/year). Thus,
      the Laoxiawan Channel may be an important metal contaminant source for the Xiang
      River. 

PMID- 27025766
TI  - Implementation of a Computerized Screening Inventory: Improved Usability Through
      Iterative Testing and Modification.
AB  - BACKGROUND: The administration of health screeners in a hospital setting has
      traditionally required (1) clinicians to ask questions and log answers, which can
      be time consuming and susceptible to error, or (2) patients to complete paper-and
      pencil surveys, which require third-party entry of information into the
      electronic health record and can be vulnerable to error and misinterpretation. A
      highly promising method that avoids these limitations and bypasses third-party
      interpretation is direct entry via a computerized inventory. OBJECTIVE: To (1)
      computerize medical and behavioral health screening for use in general medical
      settings, (2) optimize patient acceptability and feasibility through iterative
      usability testing and modification cycles, and (3) examine how age relates to
      usability. METHODS: A computerized version of 15 screeners, including behavioral
      health screeners recommended by a National Institutes of Health Office of
      Behavioral and Social Sciences Research collaborative workgroup, was subjected to
      systematic usability testing and iterative modification. Consecutive adult,
      English-speaking patients seeking treatment in an urban emergency department were
      enrolled. Acceptability was defined as (1) the percentage of eligible patients
      who agreed to take the assessment (initiation rate) and (2) average satisfaction
      with the assessment (satisfaction rate). Feasibility was defined as the
      percentage of the screening items completed by those who initiated the assessment
      (completion rate). Chi-square tests, analyses of variance, and Pearson
      correlations were used to detect whether improvements in initiation,
      satisfaction, and completion rates were seen over time and to examine the
      relation between age and outcomes. RESULTS: Of 2157 eligible patients approached,
      1280 agreed to complete the screening (initiation rate=59.34%). Statistically
      significant increases were observed over time in satisfaction (F3,1061=3.35,
      P=.019) and completion rates (F3,1276=25.44, P<.001). Younger age was associated
      with greater initiation (initiated, mean [SD], 46.6 [18.7] years; declined: 53.0
      [19.5] years, t2,155=-7.6, P<.001), higher completion (r=-.20, P<.001), and
      stronger satisfaction (r=-.23, P<.001). CONCLUSIONS: In a rapid-paced emergency
      department with a heterogeneous patient population, 59.34% (1280/2157) of all
      eligible patients initiated the computerized screener with a completion rate
      reaching over 90%. Usability testing revealed several critical principles for
      maximizing usability of the computerized medical and behavioral health screeners
      used in this study. Further work is needed to identify usability issues
      pertaining to other screeners, racially and ethnically diverse patient groups,
      and different health care settings.

PMID- 27025767
TI  - Droplet-based microfluidics in drug discovery, transcriptomics and high
      throughput molecular genetics.
AB  - Droplet-based microfluidics enables assays to be carried out at very high
      throughput (up to thousands of samples per second) and enables researchers to
      work with very limited material, such as primary cells, patient's biopsies or
      expensive reagents. An additional strength of the technology is the possibility
      to perform large-scale genotypic or phenotypic screens at the single-cell level.
      Here we critically review the latest developments in antibody screening, drug
      discovery and highly multiplexed genomic applications such as targeted genetic
      workflows, single-cell RNAseq and single-cell ChIPseq. Starting with a
      comprehensive introduction for non-experts, we pinpoint current limitations,
      analyze how they might be overcome and give an outlook on exciting future
      applications. 

PMID- 27025769
TI  - Three new drimane-type sesquiterpenoids, chaetothyrins A-C, from an endolichenic
      fungus Chaetothyriales sp.
AB  - Three new drimane-type sesquiterpenoids chaetothyrins A-C (1-3), were isolated
      from an endolichenic fungus Chaetothyriales sp. (4341B). Their structures were
      determined by analysis of MS and NMR data as well as single-crystal X-ray
      diffraction analysis. 

PMID- 27025768
TI  - Oxygen availability and spreading depolarizations provide complementary
      prognostic information in neuromonitoring of aneurysmal subarachnoid hemorrhage
      patients.
AB  - Multimodal neuromonitoring in neurocritical care increasingly includes
      electrocorticography to measure epileptic events and spreading depolarizations.
      Spreading depolarization causes spreading depression of activity
      (=isoelectricity) in electrically active tissue. If the depression is long
      lasting, further spreading depolarizations occur in still isoelectric tissue
      where no activity can be suppressed. Such spreading depolarizations are termed
      isoelectric and are assumed to indicate energy compromise. However, experimental
      and clinical recordings suggest that long-lasting spreading depolarization
      induced depression and isoelectric spreading depolarizations are often recorded
      outside of the actual ischemic zones, allowing the remote diagnosis of delayed
      cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed
      simultaneous electrocorticography and tissue partial pressure of oxygen recording
      in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed
      that both peak total depression duration per recording day and mean baseline
      tissue partial pressure of oxygen were independent predictors of outcome.
      Moreover, tissue partial pressure of oxygen preceding spreading depolarization
      was similar and differences in tissue partial pressure of oxygen responses to
      spreading depolarization were only subtle between isoelectric spreading
      depolarizations and spreading depressions. This further supports that, similar to
      clustering of spreading depolarizations, long spreading depolarization-induced
      periods of isoelectricity are useful to detect energy compromise remotely, which
      is valuable because the exact location of future developing pathology is unknown
      at the time when the neurosurgeon implants recording devices.

PMID- 27025770
TI  - Computational deconvolution of gene expression by individual host cellular
      subsets from microarray analyses of complex, parasite-infected whole tissues.
AB  - Analyses of whole organs from parasite-infected animals can reveal the entirety
      of the host tissue transcriptome, but conventional approaches make it difficult
      to dissect out the contributions of individual cellular subsets to observed gene
      expression. Computational deconvolution of gene expression data may be one
      solution to this problem. We tested this potential solution by deconvoluting
      whole bladder gene expression microarray data derived from a model of
      experimental urogenital schistosomiasis. A supervised technique was used to group
      B-cell and T-cell related genes based on their cell types, with a semi-supervised
      technique to calculate the proportions of urothelial cells. We demonstrate that
      the deconvolution technique was able to group genes into their correct cell types
      with good accuracy. A clustering-based methodology was also used to improve
      prediction. However, incorrectly predicted genes could not be discriminated using
      this methodology. The incorrect predictions were primarily IgH- and IgK-related
      genes. To our knowledge, this is the first application of computational
      deconvolution to complex, parasite-infected whole tissues. Other computational
      techniques such as neural networks may need to be used to improve prediction.

PMID- 27025771
TI  - Automated parasite faecal egg counting using fluorescence labelling, smartphone
      image capture and computational image analysis.
AB  - Intestinal parasites are a concern in veterinary medicine worldwide and for human
      health in the developing world. Infections are identified by microscopic
      visualisation of parasite eggs in faeces, which is time-consuming, requires
      technical expertise and is impractical for use on-site. For these reasons,
      recommendations for parasite surveillance are not widely adopted and parasite
      control is based on administration of rote prophylactic treatments with
      anthelmintic drugs. This approach is known to promote anthelmintic resistance, so
      there is a pronounced need for a convenient egg counting assay to promote good
      clinical practice. Using a fluorescent chitin-binding protein, we show that this
      structural carbohydrate is present and accessible in shells of ova of strongyle,
      ascarid, trichurid and coccidian parasites. Furthermore, we show that a cellular
      smartphone can be used as an inexpensive device to image fluorescent eggs and, by
      harnessing the computational power of the phone, to perform image analysis to
      count the eggs. Strongyle egg counts generated by the smartphone system had a
      significant linear correlation with manual McMaster counts (R(2)=0.98), but with
      a significantly lower coefficient of variation (P=0.0177). Furthermore, the
      system was capable of differentiating equine strongyle and ascarid eggs similar
      to the McMaster method, but with significantly lower coefficients of variation
      (P<0.0001). This demonstrates the feasibility of a simple, automated on-site test
      to detect and/or enumerate parasite eggs in mammalian faeces without the need for
      a laboratory microscope, and highlights the potential of smartphones as
      relatively sophisticated, inexpensive and portable medical diagnostic devices.

PMID- 27025772
TI  - Presence of 'ghosts' and mortality after transvenous lead extraction.
AB  - Aims: The number of cardiovascular implantable electronic devices has increased
      progressively, leading to an increased need for transvenous lead extraction (TLE)
      due to device infections. Previous studies described 'ghost' as a post-removal,
      new, tubular, mobile mass detected by echocardiography following the lead's
      intracardiac route in the right-sided heart chambers, associated with diagnosis
      of cardiac device-related infective endocarditis. We aimed to analyse the
      association between 'ghosts' assessed by transesophageal echocardiography (TEE)
      and intracardiac echocardiography (ICE) and mortality in patients undergoing TLE.
      Methods and results: We prospectively enrolled 217 patients (70 +/- 13 years; 164
      males) undergoing TLE for systemic infection (139), local device infection (67),
      and lead malfunction (11). All patients underwent TEE before and 48 h after TLE
      and ICE during TLE. Patients were allocated to two groups: either with (Group 1)
      or without (Group 2) post-procedural 'ghost'. Mid-term clinical follow-up was
      obtained in all patients (11 months, IQR 1-34 months). We identified 30 (14%)
      patients with 'ghost', after TLE. The significant predictors of 'ghost' were
      Charlson co-morbidity index (HR = 1.24, 95% CI 1.04-1.48, P = 0.03) and diagnosis
      of endocarditis assessed by ICE (HR = 1.82, 95% CI 1.01-3.29, P = 0.04).
      Mortality was higher in Group 1 than in Group 2 (28 vs. 5%; log-rank P < 0.001).
      Independent predictors of mid-term mortality were the presence of 'ghost' and
      systemic infection as the clinical presentation of device infection (HR = 3.47,
      95% CI 1.18-10.18, P = 0.002; HR = 3.39, 95% CI 1.15-9.95, P = 0.001,
      respectively). Conclusion: The presence of 'ghost' could be an independent
      predictor of mortality after TLE, thus identifying a subgroup of patients who
      need closer clinical surveillance to promptly detect any complications.

PMID- 27025774
TI  - Editorial: Statistical Signal Processing in the Analysis, Characterization and
      Detection of Alzheimer's Disease.

PMID- 27025773
TI  - An atomistic view of Hsp70 allosteric crosstalk: from the nucleotide to the
      substrate binding domain and back.
AB  - The Hsp70 is an allosterically regulated family of molecular chaperones. They
      consist of two structural domains, NBD and SBD, connected by a flexible linker.
      ATP hydrolysis at the NBD modulates substrate recognition at the SBD, while
      peptide binding at the SBD enhances ATP hydrolysis. In this study we apply
      Molecular Dynamics (MD) to elucidate the molecular determinants underlying the
      allosteric communication from the NBD to the SBD and back. We observe that local
      structural and dynamical modulation can be coupled to large-scale rearrangements,
      and that different combinations of ligands at NBD and SBD differently affect the
      SBD domain mobility. Substituting ADP with ATP in the NBD induces specific
      structural changes involving the linker and the two NBD lobes. Also, a SBD-bound
      peptide drives the linker docking by increasing the local dynamical coordination
      of its C-terminal end: a partially docked DnaK structure is achieved by combining
      ATP in the NBD and peptide in the SBD. We propose that the MD-based analysis of
      the inter domain dynamics and structure modulation could be used as a tool to
      computationally predict the allosteric behaviour and functional response of Hsp70
      upon introducing mutations or binding small molecules, with potential
      applications for drug discovery. 

PMID- 27025775
TI  - Impact of MRI-based Segmentation Artifacts on Amyloid- and FDG-PET Quantitation.
AB  - INTRODUCTION: Magnet resonance image (MRI)-based segmentations are widely used
      for clinical brain research, especially in conjunction with positron-emission
      tomography (PET). Although artifacts due to segmentation errors arise commonly,
      the impact of these artifacts on PET quantitation has not yet been investigated
      systematically. Therefore, the aim of this study was to assess the effect of
      segmentation errors on [(18)F]-AV45 and [(18)F]-FDG PET quantitation, with and
      without correction for partial volume effects (PVE). MATERIAL AND METHODS: 119
      subjects with both [(18)F]-AV45, and [(18)F]-FDG PET as well as T1-weighted MRI
      at baseline and at two-year follow-up were selected from the ADNI cohort, and
      their MRI brain images were segmented using PMOD 3.5. MRIs with segmentation
      artifacts were masked with the corresponding [(18)F]-FDG PET standard-uptake
      value (SUV) images to elucidate and quantify the impact of artifacts on PET
      analyses for six defined volumes-of-interest (VOI). Artifact volumes were
      calculated for each VOI, together with error-[%] and root-mean-square-errors
      (RMSE) in uncorrected and PVE corrected SUV results for the two PET tracers. We
      also assessed the bias in longitudinal PET data. RESULTS: Artifacts occurred most
      frequently in the parietal cortex VOI. For [(18)F]-AV45 and [(18)F]-FDG PET, the
      percentage-errors were dependent on artifact volumes. PVEC SUVs were consequently
      more distorted than were their uncorrected counterparts. In static and
      longitudinal assessment, a small subgroup of subjects with large artifacts
      (>=1500 voxels; ?5.06 cm3) accounted for much of the PET quantitation bias.
      CONCLUSION: Large segmentation artifacts need to be detected and resolved as they
      considerably bias PET quantitation, especially when PVEC is applied to PET data.

PMID- 27025776
TI  - Rosacea is linked to Parkinson's disease in Danish study.

PMID- 27025777
TI  - The effect of subcutaneous suction drains on surgical site infection in open
      abdominal surgery A prospective randomized study.
AB  - AIM: Surgical site infection (SSI) is a major problem associated with open
      abdominal surgery and related to increased morbidity and mortality rates,
      healthcare costs and also incisional hernia. A negative pressure subcutaneous
      drain reduces dead space in subcutaneous tissue by preventing accumulation of
      fluid. The aim of current study was to establish the efficacy of a subcutaneous
      drainage system for preventing SSI after open abdominal clean-contaminated
      surgery. MATERIAL AND METHODS: A total of 62 patients underwent abdominal
      surgery, between November 2014 and March 2015, were enrolled. 48 eligible
      patients, were randomized into subcutaneous drainage (DG) and no drainage group
      (NDG). Antibiotic prophylaxis was appiled to each patient. The diagnosis of
      superficial SSI was made according to the Centers for Disease Control and
      Prevention's (CDC) definition. RESULTS: The mean age of patients was 48.77 +/-
      12.62 years with a male-female ratio of 21:27. No statistical difference between
      groups was observed for age, sex, comorbidity, incision type, hemoglobin level,
      blood loss, hospital stay and operation time (P>0.05). 2 (8.7%) patients in DG
      and 8 (32%) patients in NDG had incisional SSI but no statistical difference was
      observed (P>0.05). CONCLUSION: SSI appear to be reduced with subcutaneous suction
      drains in open abdominal surgery however prospective randomized larger scaled
      studies should be performed on this topic. KEY WORDS: Abdominal surgery,
      Subcutaneous drain, Surgical site infection.

PMID- 27025778
TI  - Erratum.

PMID- 27025779
TI  - Weak-field laser phase modulation coherent control of asymptotic photofragment
      distributions.
AB  - Coherent control of the asymptotic photofragment state-resolved distributions by
      means of laser phase modulation in the weak-field limit is demonstrated
      computationally for a polyatomic molecule. The control scheme proposed applies a
      pump laser field consisting of two pulses delayed in time. Phase modulation of
      the spectral bandwidth profile of the laser field is achieved by varying the time
      delay between the pulses. The underlying equations show that such a phase
      modulation is effective in order to produce control effects on the asymptotic,
      long-time limit photofragment distributions only when the bandwidths of the two
      pulses overlap in a frequency range. The frequency overlap of the pulses gives
      rise to an interference term which is responsible for the modulation of the
      spectral profile shape. The magnitude of the range of spectral overlap between
      the pulses becomes an additional control parameter. The control scheme is
      illustrated computationally for the asymptotic photofragment state distributions
      produced from different scenarios of the Ne-Br2 predissociation. An experimental
      application of the control scheme is found to be straightforward.

PMID- 27025780
TI  - Efficacy of Carperitide in Hemodialysis Patients Undergoing Cardiac Surgery.
AB  - PURPOSE: Recently, performance of cardiac surgery in hemodialysis patients has
      increased, but the mortality rate is high. METHODS: We retrospectively examined
      the early and long-term outcomes in 128 dialysis patients who underwent cardiac
      surgery with or without carperitide infusion and were followed for 2 years. Sixty
      three patients received carperitide infusion during surgery and 65 patients did
      not. RESULTS: The hospital mortality rate was 1.6% in the carperitide group and
      12.3% in the non-carperitide group, being significantly lower in the carperitide
      group. The 2-year actuarial survival rate was 90.5% +/- 3.7% in the carperitide
      group, and 76.9% +/- 5.2% in the non-carperitide group, while the major adverse
      cardiovascular and cerebrovascular events (MACCE)-free rate at 2 years
      postoperatively was 90.5% +/- 3.7% in the carperitide group and 67.7% +/- 5.8% in
      the non-carperitide group. CONCLUSIONS: These findings suggest that carperitide
      improves the early postoperative outcome in dialysis patients undergoing cardiac
      surgery, as has already been demonstrated in non-dialysis patients. An early
      postoperative cardioprotective effect of carperitide and improvement of renal
      function in oliguric patients might have contributed to this outcome. However,
      this was a retrospective study, so a prospective investigation is required to
      demonstrate the mechanisms involved. In addition, further evaluation of the long
      term results would be desirable.

PMID- 27025781
TI  - Silicon oxycarbide glass-graphene composite paper electrode for long-cycle
      lithium-ion batteries.
AB  - Silicon and graphene are promising anode materials for lithium-ion batteries
      because of their high theoretical capacity; however, low volumetric energy
      density, poor efficiency and instability in high loading electrodes limit their
      practical application. Here we report a large area (approximately 15 cm * 2.5 cm)
      self-standing anode material consisting of molecular precursor-derived silicon
      oxycarbide glass particles embedded in a chemically-modified reduced graphene
      oxide matrix. The porous reduced graphene oxide matrix serves as an effective
      electron conductor and current collector with a stable mechanical structure, and
      the amorphous silicon oxycarbide particles cycle lithium-ions with high Coulombic
      efficiency. The paper electrode (mass loading of 2 mg cm(-2)) delivers a charge
      capacity of ~588 mAh g(-1)electrode (~393 mAh cm(-3)electrode) at 1,020th cycle
      and shows no evidence of mechanical failure. Elimination of inactive ingredients
      such as metal current collector and polymeric binder reduces the total electrode
      weight and may provide the means to produce efficient lightweight batteries.

PMID- 27025782
TI  - Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in
      Multiple Sclerosis Using Depth-Sensing Computer Vision.
AB  - BACKGROUND: Sensor-based recordings of human movements are becoming increasingly
      important for the assessment of motor symptoms in neurological disorders beyond
      rehabilitative purposes. ASSESS MS is a movement recording and analysis system
      being developed to automate the classification of motor dysfunction in patients
      with multiple sclerosis (MS) using depth-sensing computer vision. It aims to
      provide a more consistent and finer-grained measurement of motor dysfunction than
      currently possible. OBJECTIVE: To test the usability and acceptability of ASSESS
      MS with health professionals and patients with MS. METHODS: A prospective, mixed
      methods study was carried out at 3 centers. After a 1-hour training session, a
      convenience sample of 12 health professionals (6 neurologists and 6 nurses) used
      ASSESS MS to capture recordings of standardized movements performed by 51
      volunteer patients. Metrics for effectiveness, efficiency, and acceptability were
      defined and used to analyze data captured by ASSESS MS, video recordings of each
      examination, feedback questionnaires, and follow-up interviews. RESULTS: All
      health professionals were able to complete recordings using ASSESS MS, achieving
      high levels of standardization on 3 of 4 metrics (movement performance, lateral
      positioning, and clear camera view but not distance positioning). Results were
      unaffected by patients' level of physical or cognitive disability. ASSESS MS was
      perceived as easy to use by both patients and health professionals with high
      scores on the Likert-scale questions and positive interview commentary. ASSESS MS
      was highly acceptable to patients on all dimensions considered, including
      attitudes to future use, interaction (with health professionals), and overall
      perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with
      greater ambivalence arising from the need to alter patient interaction styles.
      There was little variation in results across participating centers, and no
      differences between neurologists and nurses. CONCLUSIONS: In typical clinical
      settings, ASSESS MS is usable and acceptable to both patients and health
      professionals, generating data of a quality suitable for clinical analysis. An
      iterative design process appears to have been successful in accounting for
      factors that permit ASSESS MS to be used by a range of health professionals in
      new settings with minimal training. The study shows the potential of shifting
      ubiquitous sensing technologies from research into the clinic through a design
      approach that gives appropriate attention to the clinic environment.

PMID- 27025783
TI  - Modeling and design of a cone-beam CT head scanner using task-based imaging
      performance optimization.
AB  - Detection of acute intracranial hemorrhage (ICH) is important for diagnosis and
      treatment of traumatic brain injury, stroke, postoperative bleeding, and other
      head and neck injuries. This paper details the design and development of a cone
      beam CT (CBCT) system developed specifically for the detection of low-contrast
      ICH in a form suitable for application at the point of care. Recognizing such a
      low-contrast imaging task to be a major challenge in CBCT, the system design
      began with a rigorous analysis of task-based detectability including critical
      aspects of system geometry, hardware configuration, and artifact correction. The
      imaging performance model described the three-dimensional (3D) noise-equivalent
      quanta using a cascaded systems model that included the effects of scatter,
      scatter correction, hardware considerations of complementary metal-oxide
      semiconductor (CMOS) and flat-panel detectors (FPDs), and digitization bit depth.
      The performance was analyzed with respect to a low-contrast (40-80 HU), medium
      frequency task representing acute ICH detection. The task-based detectability
      index was computed using a non-prewhitening observer model. The optimization was
      performed with respect to four major design considerations: (1) system geometry
      (including source-to-detector distance (SDD) and source-to-axis distance (SAD));
      (2) factors related to the x-ray source (including focal spot size, kVp, dose,
      and tube power); (3) scatter correction and selection of an antiscatter grid; and
      (4) x-ray detector configuration (including pixel size, additive electronics
      noise, field of view (FOV), and frame rate, including both CMOS and a-Si:H FPDs).
      Optimal design choices were also considered with respect to practical constraints
      and available hardware components. The model was verified in comparison to
      measurements on a CBCT imaging bench as a function of the numerous design
      parameters mentioned above. An extended geometry (SAD = 750 mm, SDD  = 1100 mm)
      was found to be advantageous in terms of patient dose (20 mGy) and scatter
      reduction, while a more isocentric configuration (SAD = 550 mm, SDD  = 1000 mm)
      was found to give a more compact and mechanically favorable configuration with
      minor tradeoff in detectability. An x-ray source with a 0.6 mm focal spot size
      provided the best compromise between spatial resolution requirements and x-ray
      tube power. Use of a modest anti-scatter grid (8:1 GR) at a 20 mGy dose provided
      slight improvement (~5-10%) in the detectability index, but the benefit was lost
      at reduced dose. The potential advantages of CMOS detectors over FPDs were
      quantified, showing that both detectors provided sufficient spatial resolution
      for ICH detection, while the former provided a potentially superior low-dose
      performance, and the latter provided the requisite FOV for volumetric imaging in
      a centered-detector geometry. Task-based imaging performance modeling provides an
      important starting point for CBCT system design, especially for the challenging
      task of ICH detection, which is somewhat beyond the capabilities of existing CBCT
      platforms. The model identifies important tradeoffs in system geometry and
      hardware configuration, and it supports the development of a dedicated CBCT
      system for point-of-care application. A prototype suitable for clinical studies
      is in development based on this analysis.

PMID- 27025784
TI  - Growth of semiconducting single-wall carbon nanotubes with a narrow band-gap
      distribution.
AB  - The growth of high-quality semiconducting single-wall carbon nanotubes with a
      narrow band-gap distribution is crucial for the fabrication of high-performance
      electronic devices. However, the single-wall carbon nanotubes grown from
      traditional metal catalysts usually have diversified structures and properties.
      Here we design and prepare an acorn-like, partially carbon-coated cobalt
      nanoparticle catalyst with a uniform size and structure by the thermal reduction
      of a [Co(CN)6](3-) precursor adsorbed on a self-assembled block copolymer
      nanodomain. The inner cobalt nanoparticle functions as active catalytic phase for
      carbon nanotube growth, whereas the outer carbon layer prevents the aggregation
      of cobalt nanoparticles and ensures a perpendicular growth mode. The grown single
      wall carbon nanotubes have a very narrow diameter distribution centred at 1.7 nm
      and a high semiconducting content of >95%. These semiconducting single-wall
      carbon nanotubes have a very small band-gap difference of ~0.08 eV and show
      excellent thin-film transistor performance.

PMID- 27025786
TI  - Curcumin downregulates human tumor necrosis factor-alpha levels: A systematic
      review and meta-analysis ofrandomized controlled trials.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory
      mediator and its reduction is a therapeutic target in several inflammatory
      diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in
      several preclinical studies to block TNF-alpha effectively. However, clinical
      evidence has not been fully conclusive. OBJECTIVE: The aim of the present meta
      analysis was to evaluate the efficacy of curcumin supplementation on circulating
      levels of TNF-alpha in randomized controlled trials (RCTs). METHODS: The search
      included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by
      up to September 21, 2015, to identify RCTs investigating the impact of curcumin
      on circulating TNF-alpha concentration. Quantitative data synthesis was performed
      using a random-effects model, with weighed mean difference (WMD) and 95%
      confidence interval (CI) as summary statistics. Meta-regression and leave-one-out
      sensitivity analyses were performed to assess the modifiers of treatment
      response. RESULTS: Eight RCTs comprising nine treatment arms were finally
      selected for the meta-analysis. There was a significant reduction of circulating
      TNF-alpha concentrations following curcumin supplementation (WMD: -4.69pg/mL, 95%
      CI: -7.10, -2.28, p<0.001). This effect size was robust in sensitivity analysis.
      Meta-regression did not suggest any significant association between the
      circulating TNF-alpha-lowering effects of curcumin with either dose or duration
      (slope: 0.197; 95% CI: -1.73, 2.12; p=0.841) of treatment. CONCLUSION: This meta
      analysis of RCTs suggested a significant effect of curcumin in lowering
      circulating TNF-alpha concentration.

PMID- 27025785
TI  - Off-Target drug effects resulting in altered gene expression events with
      epigenetic and "Quasi-Epigenetic" origins.
AB  - This review synthesizes examples of pharmacological agents who have off-target
      effects of an epigenetic nature. We expand upon the paradigm of epigenetics to
      include "quasi-epigenetic" mechanisms. Quasi-epigenetics includes mechanisms of
      drugs acting upstream of epigenetic machinery or may themselves impact
      transcription factor regulation on a more global scale. We explore these avenues
      with four examples of conventional pharmaceuticals and their unintended, but not
      necessarily adverse, biological effects. The quasi-epigenetic drugs identified in
      this review include the use of beta-lactam antibiotics to alter glutamate
      receptor activity and the action of cyclosporine on multiple transcription
      factors. In addition, we report on more canonical epigenome changes associated
      with pharmacological agents such as lithium impacting autophagy of aberrant
      proteins, and opioid drugs whose chronic use increases the expression of genes
      associated with addictive phenotypes. By expanding our appreciation of
      transcriptomic regulation and the effects these drugs have on the epigenome, it
      is possible to enhance therapeutic applications by exploiting off-target effects
      and even repurposing established pharmaceuticals. That is, exploration of
      "pharmacoepigenetic" mechanisms can expand the breadth of the useful activity of
      a drug beyond the traditional drug targets such as receptors and enzymes.

PMID- 27025787
TI  - Proteomics of thyroid tumours provides new insights into their molecular
      composition and changes associated with malignancy.
AB  - Around 5% of the general population have palpable thyroid nodules. Although most
      thyroid tumours are benign, thyroid cancer represents the most common malignancy
      of the endocrine system, comprising mainly follicular and papillary thyroid
      carcinomas. Previous studies have shed some light on the molecular pathogenesis
      of thyroid cancer but there have not been any comprehensive mass spectrometry
      based proteomic studies of large scale to reveal protein expression differences
      between thyroid tumours and the molecular alterations associated with tumour
      malignancy. We applied data-independent acquisition mass spectrometry which
      enabled quantitative expression analysis of over 1,600 proteins from 32 specimens
      to compare normal thyroid tissue with the three most common tumours of the
      thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma.
      In follicular tumours, we found marked reduction of the tumour suppressor and
      therapeutic target extracellular protein decorin. We made the novel observation
      that TGFbeta-induced protein ig-h3 (TGFBI) was found frequently overexpressed in
      follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis
      showed changes in papillary carcinoma were associated with disruption of cell
      contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of
      differentiation markers, all hallmarks of an invasive phenotype. 

PMID- 27025788
TI  - Cytokine Signaling in Skeletal Muscle Wasting.
AB  - Skeletal muscle wasting occurs in a variety of diseases including diabetes,
      cancer, Crohn's disease, chronic obstructive pulmonary disease (COPD), disuse,
      and denervation. Tumor necrosis factor alpha (TNF-alpha) is involved in mediating
      the wasting effect. To date, a causal relationship between TNF-alpha signaling
      and muscle wasting has been established in animal models. However, results from
      clinical trials are conflicting. This is partly due to the fact that other
      factors such as TNF-like weak inducer of apoptosis (TWEAK) and interleukin 6 (IL
      6) are also involved in skeletal muscle wasting. Because muscle wasting is often
      associated with physical inactivity and reduced food intake, therapeutic
      interventions will be most effective when multiple approaches are used in
      conjunction with nutritional support and exercise.

PMID- 27025789
TI  - Allogeneic Transplantation for Patients With Advanced Myelofibrosis: Splenomegaly
      and High Serum LDH are Adverse Risk Factors for Successful Engraftment.
AB  - BACKGROUND: Thirty consecutive patients underwent hematopoietic stem cell
      transplantation for myelofibrosis (MF) at our institution. The median age at the
      time of transplant was 49 (range, 18-68) years, 74% of patients had advanced
      Dynamic International Prognostic Scoring System (DIPSS) scores, and 83% received
      reduced-intensity conditioning. PATIENTS AND METHODS: With a long follow-up of
      our patients, we analyzed disease and transplant variables that contributed to
      engraftment and outcomes. RESULTS: Neutrophil engraftment was achieved in 27
      patients (90%) at a median time of 15 (range, 10-44) days, and 19 patients (63%)
      achieved platelet recovery at a median time of 18 (range, 8-100) days.
      Splenomegaly was associated with poor neutrophil engraftment (subdistributional
      hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.21-0.83; P = .01) and
      platelet engraftment (SHR, 0.18; 95% CI, 0.07-0.48; P < .001). Increased levels
      of lactate dehydrogenase (LDH) was associated with poor platelet engraftment
      (SHR, 0.39; 95% CI, 0.16-0.94; P = .04). The median follow-up for surviving
      patients was 49 (range, 3-155) months. The 1-year cumulative incidence of
      nonrelapse mortality (NRM) and relapse were respectively, 57% (95% CI, 29%-76%)
      and 25% (95% CI, 7%-48%). Increased levels of LDH was associated with high NRM
      (SHR, 2.82; 95% CI, 1.08-7.35; P = .03). The 4-year overall survival (OS) and
      relapse-free survival (RFS) were 44% (95% CI, 29%-67%) and 37% (95% CI, 23%-61%),
      respectively. In the multivariable model, splenomegaly and Eastern Cooperative
      Oncology Group (ECOG) performance status (PS) > 1 were associated with worse OS
      (hazard ratio [HR], 5.40; 95% CI, 1.19-24.56); P = .03) and RFS (HR, 3.78; 95%
      CI, 1.01-14.06; P < .05), respectively. ECOG PS > 1 was also associated with
      worse RFS (HR, 5.00; 95% CI, 1.31-19.14; P = .02). In this patient group with
      advanced disease, DIPPS score, Lille score, Janus-Associated Kinase V617F (JAK2
      V617F) mutation status, and donor type did not predict transplant outcome.
      CONCLUSION: We confirm curative potential, but high NRM of allogeneic transplant
      for advanced MF.

PMID- 27025790
TI  - The application of directly suspended droplet microextraction for the evaluation
      of phthalic acid esters in cow's milk by gas chromatography mass spectrometry.
AB  - A simple and rapid method was developed for evaluating 16 phthalic acid esters
      (PAEs) at the MUg/kg level in a complex milk matrix using directly suspended
      droplet microextraction-gas chromatography mass spectrometry (DSDME-GC-MS). The
      different parameters for extraction and for the DSDME experiment were optimized,
      including You are free to submit the revised manuscript at a later date as a new
      submission. 10 g/L trichloroacetic acid concentration, 100 MUL cyclohexane micro
      droplet organic solvent, 1100 rpm stirring speed, 10 min extraction time and no
      salt amount. Validation experiments showed good linearity (gamma>0.9878, 0.002
      0.4 MUg/mL), satisfactory precision (RSD<11%), and good accuracy (relative
      recovery of 70.2-108%) when analyzing milk samples using the optimized method.
      The limits of detection (LODs) ranged between 0.001 and 0.2 MUg/L, and the limits
      of quantification (LOQs) ranged between 0.003 and 0.7 MUg/L for 15 PAEs. Dinonyl
      phthalate (DINP) had a low response and did not have good linearity. The proposed
      method was successfully applied for the analysis of PAEs in real milk samples.

PMID- 27025791
TI  - Liquid chromatography coupled to tandem and high resolution mass spectrometry for
      the characterisation of ofloxacin transformation products after titanium dioxide
      photocatalysis.
AB  - The characterization of pharmaceutical drugs and their transformation products
      have become an important analytical research field because its presence in the
      environment could induce bacterial resistance. Despite all efforts made by the
      scientific community, detection and structure identification of unknown chemicals
      still remains the most challenging task in non-targeted analytics. Given that,
      the objective of the present study was to develop an untargeted workflow to
      detect, quantify, identify and characterize ofloxacin and its transformation
      products (OFX TPs) after photocatalytic treatments based on TiO2 nanoparticles
      and TiO2 nanofibers. For the characterization and chemical structure assignment
      of OFX TPs, mass defect filters, mass accurate measurements (HRMS), tandem mass
      spectrometry in a q-Orbitrap (MS/HRMS) and the photocatalysis of the isotopically
      labelled ofloxacin (OFX-d3) were used. Since a large set of data was obtained in
      each run, data treatment based on statistical analysis and mass defect filtering
      was used to reduce the number of potential TP candidates from 2497 m/z peaks to
      70. Moreover, ions generated by in-source CID and by redox reactions in the
      electrospray source (ESI) were also detected and discarded from the TP candidate
      list. Moreover, the whole kinetics evolution of the generated TPs provided a
      deeper insight into the degradation mechanism and was used to propose a
      degradation pathway for the OFX in the aqueous phase. The time evolution of the
      TPs generated during the photocatalytic process using both types of catalysts
      (NPs and NFs) and different set-ups (suspended and supported conditions)
      indicated that OFX was completely removed from the aqueous solution in less than
      4h. Among the condition tested TiO2 nanoparticles in suspended conditions showed
      the fastest kinetics (k: 0.161 min(-1)).

PMID- 27025792
TI  - Serum C1q and tumor necrosis factor (TNF)-related protein 9 in women with
      Polycystic Ovary Syndrome.
AB  - AIMS: To compare CTRP9 levels in women with Polycystic Ovary Syndrome (PCOS) and
      without PCOS. Furthermore, to determine the correlation between serum CTRP9
      levels and some variety of anthropometric and biochemical parameters. METHODS:
      The study included 29 PCOS patients and 27 healthy volunteers of the same age and
      BMI. Body weight, height and waist circumference were assessed. Blood samples
      were taken for assessment of serum CTRP9 by enzyme-linked immunosorbent assay
      (ELISA) technique. In addition, blood samples were collected for fasting insulin,
      glucose, and lipid profiles, and homeostasis model of assessment-insulin
      resistance (HOMA-IR) values were calculated. RESULTS: Similar serum CTRP9 were
      found in PCOS subjects and controls (8.8+/-19.9 vs 5.0+/-7.6ng/mL). Serum CTRP9
      concentration positively correlated with serum LDL-C and total cholesterol in
      patient group. However, no correlation between CTRP9 and other biochemical and
      anthropometric variables was found. CONCLUSION: Serum CTRP9 logs of PCOS
      participants exhibit a positive association with unfavorable lipid profile in
      this report.

PMID- 27025793
TI  - The association of maternal ABO blood group with gestational diabetes mellitus in
      Japanese pregnant women.
AB  - AIMS: To investigated the association between the ABO blood group and gestational
      diabetes mellitus (GDM). MATERIALS AND METHODS: A retrospective case-control
      study was conducted using data from 5424 Japanese pregnancies. GDM screening was
      performed in the first trimester using a casual blood glucose test and in the
      second trimester using a 50-g glucose challenge test. If the screening was
      positive, a 75-g oral glucose tolerance test was performed for a GDM diagnosis,
      which was defined according to the International Association of Diabetes and
      Pregnancy Study Groups. Logistic regression was used to obtain the odds ratio
      (OR) and 95% confidence interval (CI) adjusted for traditional risk factors.
      RESULTS: Women with the A blood group (adjusted OR: 0.34, 95% CI: 0.19-0.63), B
      (adjusted OR: 0.35, 95% CI: 0.18-0.68), or O (adjusted OR: 0.39, 95% CI: 0.21
      0.74) were at decreased risk of GDM compared with those with group AB. Women with
      the AB group were associated with increased risk of GDM as compared with those
      with A, B, or O (adjusted OR: 2.73, 95% CI: 1.64-4.57). CONCLUSION: ABO blood
      groups are associated with GDM, and group AB was a risk factor for GDM in
      Japanese population.

PMID- 27025794
TI  - Metabolic memory phenomenon in diabetes mellitus: Achieving and perspectives.
AB  - Diabetes mellitus (DM) exhibits raised prevalence worldwide. There is a large
      body of evidence regarding the incidence of DM closely associates with
      cardiovascular (CV) complications. In this context, hyperglycaemia, oxidant
      stress, and inflammation are key factors that contribute in CV events and disease
      in type1 and type 2 DM, even when metabolic control was optimal and/or intensive
      glycemic control was implemented. It has been suggested that the effect of poor
      metabolic control or even transient episodes of hyperglycemia in DM associates in
      particularly with worsening ability of endogenous vasoreparative systems that are
      mediated epigenetic changes in several cells (progenitor cells, stem cells,
      mononuclears, immune cells), and thereby lead to so called "vascular glycemic
      memory" or "metabolic memory". Both terms are emphasized the fact that prior
      glucose control has sustained effects that persist even after return to more
      usual glycemic control. The mechanisms underlying the cellular "metabolic memory"
      induced by high glucose remain unclear. The review is discussed pathophysiology
      and clinical relevance of "metabolic" memory phenomenon in DM. The role of
      oxidative stress, inflammation, and epigenetics in DM and its vascular
      complications are highlighted. The effects of several therapeutic approaches are
      discussed. 

PMID- 27025795
TI  - Exploring divergent trajectories: Disorder-specific moderators of the association
      between negative urgency and dysregulated eating.
AB  - Negative urgency (i.e., the tendency to act impulsively when experiencing
      negative emotions) is a well-established risk factor for dysregulated eating
      (e.g., binge eating, loss of control eating, emotional eating). However, negative
      urgency is transdiagnostic, in that it is associated with multiple forms of
      psychopathology. It is currently unclear why some individuals with high negative
      urgency develop dysregulated eating while others experience depressive symptoms
      or problematic alcohol use. Investigating disorder-specific moderators of the
      association between negative urgency and psychopathology may help elucidate these
      divergent trajectories. The current study examined interactions among negative
      urgency and eating disorder-specific risk factors specified in the well
      established dual-pathway model of bulimic pathology (i.e., appearance pressures,
      thin-ideal internalization, body dissatisfaction, dietary restraint). We
      hypothesized that these interactions would predict dysregulated eating, but not
      depressive symptoms or problematic alcohol use. Latent moderated structural
      equation modeling was used to test this hypothesis in a large (N = 313) sample of
      female college students. Negative urgency was significantly associated with
      dysregulated eating, depressive symptoms, and problematic alcohol use. However,
      interactions among negative urgency and dual-pathway model variables were
      specific to dysregulated eating and accounted for an additional 3-5% of the
      variance beyond main effects. Findings suggest that eating disorder-specific risk
      factors may shape negative urgency into manifesting as dysregulated eating versus
      another form of psychopathology. Future research should use longitudinal designs
      to further test the impact of interactions among disorder-specific risk factors
      and negative urgency on divergent psychopathology trajectories.

PMID- 27025796
TI  - Catastrophizing and anxiety sensitivity mediate the relationship between
      persistent pain and emotional eating.
AB  - Stress-induced or "emotional eating" contributes to increased caloric intake and
      weight gain, yet models examining psychosocial factors that promote and sustain
      this behavior are incomplete. There is a need to identify explicit, clinically
      relevant mechanisms of emotional eating behavior. Pain is a common stressor
      associated with increased weight and, potentially, altered eating behaviors. The
      present study applies the Fear Avoidance Model (FAM) of pain to examine processes
      that may explain the relationship between pain and increased weight while also
      providing the opportunity to examine specific mechanisms that may encourage
      eating during a variety of stressors. Our aim is to better understand the impact
      of pain on eating behavior and the potential for the FAM to improve our
      understanding of the psychological mechanisms that promote eating during times of
      duress. A survey of 312 adults explored the link between pain experience and
      stress-induced eating, further examining the mediating effects of the
      psychological aspects of the FAM (e.g., anxiety sensitivity, catastrophizing, and
      pain-related fear). 24% of respondents reported persistent pain, and had
      significantly higher BMIs than their pain-free peers. All three FAM components
      were positively correlated with measures of emotional, external, and restrained
      eating. Anxiety sensitivity and catastrophizing significantly mediated the
      relationship between persistent pain and emotional eating behavior, while anxiety
      sensitivity alone mediated the relationship between persistent pain and external
      eating. Findings suggest pain may be associated with increased likelihood for
      emotional eating and that characteristics from FAM, in particular anxiety
      sensitivity and catastrophizing, may mediate the relationship between the
      presence of persistent pain and emotional eating behavior. Evidence-based
      treatments targeting anxiety sensitivity and catastrophizing could be useful to
      address emotional eating in individuals struggling with both weight and chronic
      pain.

PMID- 27025797
TI  - Novel Sensor Technology To Assess Independence and Limb-Use Laterality in
      Cervical Spinal Cord Injury.
AB  - After spinal cord injury (SCI), levels of independence are commonly assessed with
      standardized clinical assessments. However, such tests do not provide information
      about the actual extent of upper limb activities or the impact on independence of
      bi- versus unilateral usage throughout daily life following cervical SCI. The
      objective of this study was to correlate activity intensity and laterality of
      upper extremity activity measured by body-fixed inertial measurement units (IMUs)
      with clinical assessment scores of independence. Limb-use intensity and
      laterality of activities performed by the upper extremities was measured in 12
      subjects with cervical SCI using four IMUs (positioned on both wrists, on the
      chest, and on one wheel of the wheelchair). Algorithms capable of reliably
      detecting self-propulsion and arm activity in a clinical environment were applied
      to rate functional outcome levels, and were related to clinical independence
      measures during inpatient rehabilitation. Measures of intensity of upper
      extremity activity during self-propulsion positively correlated (p < 0.05, r =
      0.643) with independence measures related to mobility. Clinical measures of
      laterality were positively correlated (p < 0.01, r = 0.900) with laterality as
      measured by IMUs during "daily life," and increased laterality was negatively
      correlated (p < 0.01, r = -0.739) with independence. IMU sensor technology is
      sensitive in assessing and quantifying upper limb-use intensity and laterality in
      human cervical SCI. Continuous and objective movement data of distinct daily
      activities (i.e., mobility and day-to-day activities) can be related to levels of
      independence. Therefore, IMU sensor technology is suitable not only for
      monitoring activity levels during rehabilitation (including during clinical
      trials) but could also be used to assess levels of participation after discharge.

PMID- 27025798
TI  - Severe Agranulocytosis in Two Patients with Drug-induced Hypersensitivity
      Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms.

PMID- 27025799
TI  - [Ethical conflicts in scientific publishing: self-plagiarism].

PMID- 27025800
TI  - Incidence of ventilator associated pneumonia in burn patients with inhalation
      injury treated with high frequency percussive ventilation versus volume control
      ventilation: A systematic review.
AB  - BACKGROUND: Pneumonia increases mortality in burn patients with inhalation
      injuries. We evaluated whether the use of High Frequency Percussive Ventilation
      (HFPV) in burn patients with inhalation injuries can decrease rates of Ventilator
      Associated Pneumonia (VAP) compared to Volume Control Ventilation (VCV). METHODS:
      Data were gathered from PubMed, EMBASE, Web of Science, reference lists, and hand
      search. For unpublished data we searched ClinicalTrials.gov and RePORTER. We
      included observational and Randomized Controlled Trials (RCTs) that compared
      rates of VAP with the use of HFPV and VCV in adult burn patients with inhalation
      injury. Two reviewers independently extracted data from the retrieved studies and
      assessed them for eligibility, methodology, and quality. RESULTS: 281 abstracts
      were reviewed, of which 4 studies (540 patients) were included. Two were
      observational and two were RCTs. All studies had moderate risk of bias. One study
      had low external validity while others had moderate external validity. The two
      observational studies found non-concordant results. One study found a 24%
      statistically significant reduction in the rates of VAP while the other found no
      difference. The two RCTs had small sample sizes. There was no significant
      difference in VAP rates between HFPV and VCV. The VCV arms of the four studies
      were heterogeneous. Only one study used low tidal volumes, whereas the rest used
      high tidal volumes in the VCV arm. CONCLUSION: Evidence about decreased incidence
      of VAP in burn patients with inhalation injuries who are on HFPV compared to
      those on VCV is inconclusive. Although enhanced airway clearance by HFPV was
      thought to play a role in decreasing VAP in this population, high tidal volume in
      the VCV arms could be a confounding factor that should be eliminated in future
      studies before a firm conclusion can be reached. More RCTs comparing HFPV to low
      tidal volume VCV are needed.

PMID- 27025801
TI  - Early management in children with burns: Cooling, wound care and pain management.
AB  - INTRODUCTION: Early management in burns, i.e. prior to admission in a burn
      center, is essential for an optimal process and outcome of burn care. Several
      publications have reported suboptimal early management, including low levels of
      pain medication after trauma, especially in children. The aim of this study was
      to evaluate the current practice in the Netherlands and factors related to early
      management in pediatric burns, i.e. cooling, wound covering and pain management.
      To study possible change and improvement over time, two study periods were
      compared. METHODS: This study involved two periods; January 2002-March 2004
      (period 1) and January 2007-August 2008 (period 2). All children (0-15 years of
      age) with acute burns admitted within 24h after burn to one of the three Dutch
      Burn centers with a formal referral were eligible. Data were obtained from
      patient records, both retrospectively and prospectively. RESULTS: A total of 323
      and 299 children were included in periods 1 and 2, respectively. The vast
      majority of children in both study periods had been cooled before admission
      (>90%). Over time, wound covering increased significantly (from 64% to 89%) as
      well as pain treatment (from 68% to 79%). Predominantly paracetamol and morphine
      were used. Referral from ambulance services (OR=41.4, 95%CI=16.6-103.0) or
      general practitioners (OR=59.7, 95%CI=25.1-141.8) were strong independent
      predictors for not receiving pre-burn center pain medication. On the other hand,
      flame burns (OR=0.2, 95%CI=0.1-0.5) and more extensive burns (TBSA 5-10%: OR=0.4,
      95%CI=-0.2 to 0.8; TBSA>=10%: OR=0.2, 95%CI=0.1-0.4) were independent predictors
      of receiving pain medication. CONCLUSION: Referring physicians of children with
      burns were overall well informed: they cool the wound after burns and cover it
      before transport to prevent hypothermia and reduce the pain. Additional studies
      should be conducted to clarify the duration and temperature for cooling to be
      effective. Furthermore, there is room and a need for improvement regarding early
      pain management.

PMID- 27025802
TI  - Postnatal Development of the Craniofacial Skeleton in Male C57BL/6J Mice.
AB  - C57BL/6J is one of the most commonly used inbred mouse strains in biomedical
      research, including studies of craniofacial development and teratogenic studies
      of craniofacial malformation. The current study quantitatively assessed the
      development of the skull in male C57BL/6J mice by using high-resolution 3D
      imaging of 55 landmarks from 48 male mice over 10 developmental time points from
      postnatal day 0 to 90. The growth of the skull plateaued at approximately
      postnatal day 60, and the shape of the skull did not change markedly thereafter.
      The amount of asymmetry in the craniofacial skeleton seemed to peak at birth, but
      considerable variation persisted in all age groups. For C57BL/6J male mice,
      postnatal day 60 is the earliest time point at which the skull achieves its adult
      shape and proportions. In addition, C57BL/6J male mice appear to have an inherent
      susceptibility to craniofacial malformation. 

PMID- 27025803
TI  - Plasma Metabolomics of Common Marmosets (Callithrix jacchus) to Evaluate Diet and
      Feeding Husbandry.
AB  - Common marmosets (Callithrix jacchus) are an important NHP model for the study of
      human aging and age-related diseases. However, the full potential of marmosets as
      a research model has not been realized due to a lack of evidence-based,
      standardized procedures for their captive management, especially regarding diet
      and feeding husbandry. In the present study, we conducted a high-resolution
      metabolomics analysis of plasma from marmosets from a 3-mo dietary crossover
      study to determine whether significant metabolic differences occur with a
      semisynthetic chemically defined (purified) diet as needed for controlled
      nutrition research. Marmosets were fed a standard, diverse-ingredient diet,
      followed by a semisynthetic purified diet, and then were switched back to the
      standard diet. The standard diet used in this analysis was specific to the animal
      facility, but it is similar in content to the diets currently used for other
      marmoset colonies. High-resolution metabolomics of plasma with liquid
      chromatography-mass spectrometry and bioinformatics was used to measure metabolic
      differences. The concentration of the essential amino acids methionine,
      leucine/isoleucine, lysine, and threonine were higher when marmosets were fed the
      purified diet. In contrast, phenylalanine concentrations were higher during
      exposure to the standard diet. In addition, metabolic pathway enrichment and
      analysis revealed differences among metabolites associated with dopamine
      metabolism and the carnitine shuttle. These results show that diet-associated
      differences in metabolism occur in marmosets and suggest that additional
      nutritional studies with detailed physiologic characterization are needed to
      optimize standard and purified diets for common marmosets. 

PMID- 27025804
TI  - The Population Genetic Composition of Conventional and SPF Colonies of Rhesus
      Macaques (Macaca mulatta) at the Caribbean Primate Research Center.
AB  - The SPF breeding program at the Caribbean Primate Research Center supplies Indian
      origin rhesus macaques of known genetic and virologic background for biomedical
      research. In this study, population genetic analyses using 14 short tandem-repeat
      sequences showed that the SPF colony has remained genetically homogenous over
      time, with sufficient amounts of heterozygosity and minimal stratification from
      its founders. Intergenerational studies indicated that an average of 7 alleles
      have been retained, inbreeding levels have remained low, and the degree of Indian
      ancestry is one of the highest among several national primate research centers.
      The relative low genetic diversity in the free-ranging population as well as in
      the captive SPF and conventional colonies when compared with that of other
      primate centers indicates that the free-ranging population, from which the
      captive-colony animals were derived, has experienced significant founder effects
      and genetic drift during the years after its establishment. This study supports
      the historical origin of the free-ranging population and confirms the high value
      of this resource for biomedical research. Current genetic diversity levels within
      the SPF colony can be ensured with the practice of colony management approaches
      such as equalizing male:female ratios in each SPF breeding group and increasing
      breeding group sizes. Introducing new Indian-origin macaques from other captive
      colonies might help to maximize the genetic diversity of the breeding stock.
      Furthermore, genetic estimates must be used to rank breeders according to their
      genetic value or their genome uniqueness to increase founder-genome
      representation and curb future genetic bottlenecks and allele loss.

PMID- 27025805
TI  - Normal Electrocardiogram of Bama Miniature Pigs (Sus scrofa domestica).
AB  - This study determined the normal ECG patterns and values for Bama miniature pigs.
      Standard limb-lead ECG were recorded from 120 clinically healthy, unanesthetized
      piglets (age, 2 to 4 mo). The values for the ECG parameters (mean +/- 1 SD) were:
      heart rate, 125.56 +/- 18.80 bpm; P amplitude, 0.11 +/- 0.03 mV; QRS amplitude,
      0.63 +/- 0.31 mV; P duration, 43.99 +/- 5.98 ms; QRS complex, 55.27 +/- 7.02 ms;
      RR interval, 487.55 +/- 77.32 ms; PR interval, 90.72 +/- 11.94 ms; QT interval,
      244.72 +/- 25.27 ms; and mean electrical axis, 22.2 +/- 80.3 degrees . The P
      waves were predominantly positive in leads I and II and in the augmented unipolar
      limb aVF lead; by comparison, the QRS patterns were less uniform. The T waves
      were slightly positive in leads II, III, and aVF. The determination and
      publication of the normal ECG patterns and values of Bama minipigs facilitates
      understanding of the electrocardiographic changes that arise under experimental
      conditions. 

PMID- 27025806
TI  - The Uterus Duplex Bicollis, Vagina Simplex of Female Chinchillas.
AB  - The available literature describing the morphology of the female chinchilla's
      uterine cervix varies and includes phrases such as 'the cervical canal,' 'a
      single cervix,' and 'the cervix;' alternatively, some publications describe 2
      cervices. In this report, we provide an anatomically correct and definitive
      description of the uterine cervical morphology of the laboratory chinchilla. We
      further propose revised, anatomically precise nomenclature to characterize the
      female chinchilla reproductive tract as a whole. 

PMID- 27025807
TI  - Temperature Preference in IAF Hairless and Hartley Guinea Pigs (Cavia porcellus).
AB  - The Hairless strain of guinea pigs (Cavia porcellus) is the result of a
      spontaneous recessive mutation first identified at the Institute Armand Frappier
      (IAF) in 1978. Despite the longstanding availability of this strain, little is
      known about its thermoregulatory behavior. The aim of this study was to determine
      temperature preference in Hartley and Hairless guinea pigs by observing each
      strain in a ring-shaped apparatus containing a nonlinear temperature gradient.
      Temperatures were maintained by separately controlled heating mats lining the
      apparatus. Set point temperatures ranged from 24 to 38  degrees C. Guinea pigs
      (Hartley female, Hairless female, and Hairless male guinea pigs; n = 8 each
      group) were placed either singly or in pairs at 1 of the 8 randomized starting
      points within the apparatus. Subjects were observed for 30 min and coded for
      location within the temperature gradient by both frequency and duration. When
      placed singly in the apparatus, all 3 groups spent more time in the 30  degrees C
      zones. However, when placed as pairs with a cagemate, Hartley female guinea pigs
      spent more time in the cooler range of temperatures from 24 to 30  degrees C,
      whereas Hairless guinea pigs preferred a range of 30 to 38  degrees C. These
      results confirm a temperature preference of 30 +/- 2  degrees C for both Hartley
      and Hairless guinea pigs when singly housed. However, data from the paired
      housing condition suggest that context plays an important role in
      thermoregulatory behavior. 

PMID- 27025808
TI  - Effects of Nominal Differences in Cage Height and Floor Space on the Wellbeing of
      Rabbits.
AB  - The 8th edition of the Guide for the Care and Use of Laboratory Animals
      recommends a cage height of 16 in. for rabbits, compared with 14 in. in the
      previous edition. In contrast, the Animal Welfare Act Regulations prescribes a
      cage height of 14 in. for rabbits. A review of the literature failed to identify
      published data that support an advantage to rabbits having 16 in. of cage height
      compared with 14 or 15 in. The study described here evaluated the effect of a 3
      in. difference in cage height on the health, growth, behavior, and overall
      wellbeing of rabbits. Groups of 10 New Zealand white rabbits were housed in cages
      that provided either 15 in. of interior cage height (720 in(2) of floor space) or
      18 in. of interior height (784 in(2) of floor space). The rabbits were observed
      during 25 periods (1 h each) over 7 wk, and various behavioral parameters were
      scored. In addition, rabbits were weighed weekly, and general clinical health was
      assessed. After 4 wk, the groups were switched to the alternate housing. No
      significant differences in body weight gain or behavioral parameters were
      detected between groups housed in cages with different heights and amounts of
      floor space, nor were significant behavioral differences noted in individual
      rabbits when moved from one cage type to the other. In addition, all rabbits
      remained clinically healthy throughout the study. These results demonstrate that
      these differences in interior cage height neither benefit nor harm rabbits. 

PMID- 27025809
TI  - Association of Primate Veterinarians 2014 Nonhuman Primate Housing Survey.
AB  - The Board of Directors of the Association of Primate Veterinarians supported
      conducting a survey to determine how NHP were housed in USDA-registered research
      facilities. The data generated were to be used to refute allegations in a
      petition filed with the USDA by the New England Antivivisectionist Society, which
      alleged that the proportion of NHP housed singly had not improved since the
      implementation of the standards contained in S3.81 of the Animal Welfare
      Regulations. The survey gathered housing information on approximately 90% of the
      NHP housed in research facilities in FY2014. That information documented that the
      number of NHP housed in groups or pairs has increased by 20 percentage points to
      84% since the USDA's survey conducted in 2000 and 2001. This article describes
      the methodology and approach used to conduct the survey, summarizes the data
      obtained, and discusses the meaning of those data. 

PMID- 27025811
TI  - Tattooing Various Combinations of Ears, Tail, and Toes to Identify Mice Reliably
      and Permanently.
AB  - Uniquely identifying research animals is a widespread and essential procedure.
      Potential disadvantages of commonly used identification methods such as toe
      clipping, ear punching, and ear tagging include tissue loss and adverse effects
      in physiologic homeostasis and animal behavior. In addition, the labels produced
      by using these methods can become unreadable, potentially leading to
      misidentification. In this study, we proposed a combined approach involving ear,
      tail, and toe tattooing that can be used to permanently identify mice regardless
      of their age. Four groups (neonatal and adult C57BL/6J [black] and CD1 [white]
      mice) were used. Single- or 2-color tattooing (ear, tail, or toe or combinations
      thereof) was performed to identify a defined or unlimited number of mice,
      respectively. Tail tattooing using both green and red pastes was suitable for
      identifying white-haired neonatal mice as early as postnatal day 1, whereas toe
      tattooing with green paste was an effective alternative approach for labeling
      black-haired mouse pups. In comparison, single-color (green) or 2-color (green
      and red) ear tattooing identified both white and black adult mice older than 3
      wk. Ear tattooing can be adapted to labeling an unlimited number of adult mice by
      adding the cage number. We conclude that tattooing various combinations of the
      ears, tail, and toes provides an easy and permanent approach for identifying mice
      of all ages with minimal disturbance to the animals. 

PMID- 27025810
TI  - Factors in the Selection of Surface Disinfectants for Use in a Laboratory Animal
      Setting.
AB  - Because surface disinfectants are an important means of pathogen control within
      laboratory animal facilities, these products must have an appropriate spectrum of
      antimicrobial activity. However, many other factors must also be considered,
      including effects on human health, environmental safety, and animal behavior.
      Aqueous solutions of sodium hypochlorite often are considered to be the 'gold
      standard' for surface disinfection, but these products can be corrosive, caustic,
      and aversive in odor. This study was designed to identify disinfectants that are
      as effective as hypochlorite solutions but more acceptable for use in a
      laboratory animal setting. An antiviral disinfectant-efficacy assay was developed
      by using viral vectors that expressed green fluorescence protein as surrogates
      for wild-type viruses of concern in laboratory animals. Efficacy testing revealed
      that most of the products were highly effective when used against viral vectors
      in suspension. However, when the disinfectants were challenged by buffering virus
      in protein or drying virus on nonporous surfaces, the hypochlorite and
      peroxymonosulfate products performed the best. Review of safety data sheets for
      the agents indicated that a peroxide-based product was considerably safer than
      the other products tested and that the pH of most products was not conducive to
      disposal down a drain. Behavioral testing of Swiss Webster, C57Bl/6, and BALB/c
      mice showed that the hypochlorite- and peroxide-based products were clearly
      aversive, given that the mice consistently avoided these products. All of these
      factors must be considered when choosing the appropriate disinfectant. 

PMID- 27025812
TI  - Comparison of 2-Ethyl-Cyanoacrylate and 2-Butyl-Cyanoacrylate for Use on the
      Calvaria of CD1 Mice.
AB  - Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron
      Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although
      once used in clinical medicine as skin adhesives, these products caused tissue
      toxicity and thus their use in live tissue was discontinued. SCCA were replaced
      by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St
      Paul, Minnesota), which were found to be less toxic than the short-chain
      formulations. Some researchers prefer to use SCCA due to the belief that they
      create a stronger bond than do the longer-chain counterparts. In survival
      surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation,
      and bone regeneration in the calvaria of control (naive), surgery-only, SCCA
      treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery,
      all mice except those treated with SCCA showed statistically similar bone
      measurements to those of the naive control group. The SCCA group had
      significantly less bone regeneration than did all other groups. These results
      suggest that the application of SCCA causes bone damage resulting in the loss of
      bone regeneration. This finding may assist investigators in choosing a tissue
      glue for their studies and may support the IACUC in advocating the use of
      pharmaceutical-grade tissue glues. 

PMID- 27025813
TI  - Effects of Axial Vibration on Needle Insertion into the Tail Veins of Rats and
      Subsequent Serial Blood Corticosterone Levels.
AB  - Blood collection is commonplace in biomedical research. Obtaining sufficient
      sample while minimizing animal stress requires significant skill and practice.
      Repeated needle punctures can cause discomfort and lead to variable release of
      stress hormones, potentially confounding analysis. We designed a handheld device
      to reduce the force necessary for needle insertion by using low-frequency, axial
      (forward and backward) micromotions (that is, vibration) delivered to the needle
      during venipuncture. Tests with cadaver rat-tail segments (n = 18) confirmed that
      peak insertion forces were reduced by 73% on average with needle vibration. A
      serial blood-sampling study was then conducted by using Sprague-Dawley rats
      divided into 2 groups based on needle condition used to cause bleeds: vibration
      on (n = 10) and vibration off (n = 9). On 3 days (1 wk apart), 3 tail-vein blood
      collections were performed in each subject at 1-h intervals. To evaluate
      associated stress levels, plasma corticosterone concentration was quantified by
      radioimmunoassay and behavior (that is, movement and vocalization) was scored by
      blinded review of blood-sampling videos. After the initial trial, average
      corticosterone was lower (46% difference), the mean intrasubject variance trended
      lower (72%), and behavioral indications of stress were rated lower for the
      vibration-on group compared with the vibration-off group. Adding controlled
      vibrations to needles during insertion may decrease the stress associated with
      blood sampling from rats--an important methodologic advance for investigators
      studying and assessing stress processes and a refinement over current blood
      sampling techniques.

PMID- 27025814
TI  - An Impedance-Based Model for the Assessment of Cardiopulmonary Function in
      Rabbits.
AB  - Improving the quality of physiologic data collected from research animals is most
      easily accomplished by collecting as much information as possible from a single
      subject, thereby reducing animal use and error associated with satellite groups.
      We investigated the feasibility of using a large-animal implantable telemetry
      device in New Zealand white rabbits (n = 6). The first task was to develop an
      implantation technique that yielded calibrated tidal volume (Vt) measurements
      that were within 10% of those obtained simultaneously from a pneumotachograph, a
      low-noise electrocardiogram, and stable blood pressure. The second task was to
      challenge implanted rabbits with the respiratory stimulant doxapram to assess
      linearity of the calibration across a range of Vt. Of the 3 electrode placements
      attempted, only one resulted in calibrations consistently below 10% error.
      Optimal electrode placement resulted in calibrated Vt measurements within 1.7% +/
      0.3% of those obtained from a pneumotachograph during normal tidal breathing,
      7.3% +/- 0.7% of those after saline injection, and 6.0% +/- 0.5% of those after
      doxapram injection. The Vt range was 9 to 15 mL for normal tidal breathing and
      saline injection and 25 to 30 mL after doxapram injection. Increases in mean
      arterial pressure of 25.0 +/- 6.82 mm Hg and decreases in heart rate of 56.3 +/-
      6.82 bpm were associated with doxapram injection only. Our findings represent the
      first time that multiple cardiopulmonary endpoints have been assessed by
      telemetry in conscious, restrained rabbits. Whether animal position affects
      calibration accuracy warrants investigation. 

PMID- 27025815
TI  - Measurement of Tear Production in English Angora and Dutch Rabbits.
AB  - The purpose of this study was to establish normal values for tear production
      tests in different breeds of domestic rabbits. Healthy adult rabbits (n = 60; 120
      eyes) of 2 different breeds (English angora and Dutch; n = 15 of each sex and
      breed) were used in this study. Tear production was measured by using the 1-min
      Schirmer tear test (STT), phenol red thread test (PRTT), and endodontic absorbent
      paper point tear test (EAPTT). In addition, horizontal palpebral fissure length
      was evaluated as a measure of ocular adnexal dimensions. Tear production (mean +/
      1 SD) in English angora rabbits was 5.4 +/- 1.6 mm/min according to the STT,
      25.0 +/- 2.7 mm in 15 s for the PRTT, and 18.8 +/- 2.1 mm/min by the EAPTT; in
      Dutch rabbits, these values were 4.6 +/- 1.2 mm/min, 23.6 +/- 2.3 mm in 15 s, and
      16.9 +/- 1.7 mm/min, respectively. Only the EAPTT revealed a significant
      difference in tear production between English Angora and Dutch rabbits. These
      results provide reference values for tear production in English Angora and Dutch
      rabbits according to 3 different quantitative tear film assessment methods. 

PMID- 27025816
TI  - Pharmacokinetics of Ceftiofur Crystalline-Free Acid in Clinically Healthy Dogs
      (Canis lupus familiaris).
AB  - Economical, injectable antibiotics are beneficial when clinical manifestations of
      an animal model prevent the use of oral antibiotics. Ceftiofur crystalline-free
      acid (CCFA) is an injectable, sustained-release form of ceftiofur, a third
      generation cephalosporin that is labeled for use in swine, cattle, and horses.
      Because CCFA is an economical, injectable antibiotic that could be of value for
      use in research dogs, the objective of this study was to determine the
      pharmacokinetic properties of CCFA in apparently healthy dogs and to determine
      the minimal inhibitory concentrations of ceftiofur for veterinary pathogens
      cultured during 2011 through 2014 from the respiratory system, integumentary
      system, and urinary system of dogs. The study population comprised of 5 dogs
      (age, 1 y; weight, 24.7 to 26.9 kg) that were deemed healthy after no
      abnormalities were found on physical exam, CBC analysis, and clinical chemistry
      panel. Each dog received CCFA at 5.0 mg/kg SC, and blood samples were collected
      before administration of CCFA and at 1, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144,
      168, 192, 216, and 240 h after injection. The maximal plasma concentration (mean
      +/- 1 SD) of CCFA was 1.98 +/- 0.40 MU g/mL, time to reach maximal concentration
      was 22.3 +/- 8.9 h, half-life was 56.6 +/- 16.9 h, and AUC0-last was 124.98 +/-
      18.45 MU g-h/mL. The minimal inhibitory concentrations of ceftiofur ranged from
      <= 0.25 to >= 8.0 MU g/mL; ceftiofur was most effective against Pasteurella spp.,
      Proteus spp., and Escherichia coli haemolytica and least effective against
      Bordatella bronchiseptica, Enterococcus spp., and Pseudomonas aeruginosa. 

PMID- 27025817
TI  - Microsurgery-aided in-situ force probing reveals extensibility and viscoelastic
      properties of individual stress fibers.
AB  - Actin-myosin filament bundles (stress fibers) are critical for tension generation
      and cell shape, but their mechanical properties are difficult to access. Here we
      propose a novel approach to probe individual peripheral stress fibers in living
      cells through a microsurgically generated opening in the cytoplasm. By applying
      large deformations with a soft cantilever we were able to fully characterize the
      mechanical response of the fibers and evaluate their tension, extensibility,
      elastic and viscous properties. 

PMID- 27025818
TI  - Quantitation of Bedaquiline: Points of Attention.

PMID- 27025819
TI  - Isolation of Hepatitis E Virus From Breast Milk During Acute Infection.

PMID- 27025820
TI  - Whole-genome Sequencing Used to Investigate a Nationwide Outbreak of Listeriosis
      Caused by Ready-to-eat Delicatessen Meat, Denmark, 2014.
AB  - BACKGROUND: Listeriosis is a serious foodborne infection. Outbreaks of
      listeriosis occur rarely, but have often proved difficult to solve. In June 2014,
      we detected and investigated a listeriosis outbreak in Denmark using patient
      interviews and whole-genome sequencing (WGS). METHODS: We performed WGS on
      Listeria monocytogenes isolates from patients and available isolates from ready
      to-eat foods and compared them using single-nucleotide polymorphism (SNP)
      analysis. Case patients had L. monocytogenes with <=3 SNPs (the outbreak strain)
      isolated in September 2013-December 2014. Through interviews, we established case
      patients' food and clinical histories. Food production facilities were inspected
      and sampled, and we performed trace-back/trace-forward of food delivery chains.
      RESULTS: In total, 41 cases were identified; 17 deaths occurred (41%). An isolate
      from a delicatessen meat (spiced meat roll) from company A was identical to the
      outbreak strain. Half of the patients were infected while
      hospitalized/institutionalized; institutions were supplied food by company A. The
      outbreak strain was repeatedly isolated from further samples taken within this
      company and within companies in its distribution chain. Products from company A
      were traced and recalled from >6000 food establishments, after which the outbreak
      ended. CONCLUSIONS: Ready-to-eat spiced meat roll from a single production
      facility caused this outbreak. The product, served sliced and cold, is popular
      among the elderly; serving it at hospitals probably contributed to the high case
      fatality rate. WGS used for patient isolates and isolates from food control
      inspections, coupled with routine epidemiological follow-up, was instrumental in
      swiftly locating the source of infections, preventing further illnesses and
      deaths.

PMID- 27025821
TI  - Investigation of Legionella pneumophila Outbreak: Effectiveness of Clinical and
      Genomic Methods.

PMID- 27025822
TI  - Emerging Resistance, New Antimicrobial Agents  ...  but No Tests! The Challenge
      of Antimicrobial Susceptibility Testing in the Current US Regulatory Landscape.
AB  - Accurate and timely performance of antimicrobial susceptibility testing (AST) by
      the clinical laboratory is paramount to combating antimicrobial resistance. The
      ability of laboratories in the United States to effectively perform ASTs is
      challenged by several factors. Some, such as new resistance mechanisms and the
      associated evolution of testing recommendations and breakpoints, are inevitable.
      Others are entirely man-made. These include unnecessarily strict US Food and Drug
      Administration (FDA) limitations on how commercial AST systems can be used for
      diagnostic testing, the absence of up-to-date performance data on these systems,
      and the lack of commercially available FDA-cleared tests for newer antimicrobial
      agents or for older agents with updated breakpoints. This viewpoint will
      highlight contemporary AST challenges faced by the clinical laboratory, and
      propose some solutions.

PMID- 27025823
TI  - Periodic Illness Associated With Epstein-Barr Virus: A New Diagnosis After a 22
      Year Follow-up.

PMID- 27025824
TI  - Handling Time-dependent Variables: Antibiotics and Antibiotic Resistance.
AB  - Elucidating quantitative associations between antibiotic exposure and antibiotic
      resistance development is important. In the absence of randomized trials,
      observational studies are the next best alternative to derive such estimates.
      Yet, as antibiotics are prescribed for varying time periods, antibiotics
      constitute time-dependent exposures. Cox regression models are suited for
      determining such associations. After explaining the concepts of hazard, hazard
      ratio, and proportional hazards, the effects of treating antibiotic exposure as
      fixed or time-dependent variables are illustrated and discussed. Wider acceptance
      of these techniques will improve quantification of the effects of antibiotics on
      antibiotic resistance development and provide better evidence for guideline
      recommendations.

PMID- 27025825
TI  - Long-term Follow-up of Patients With Lyme Disease: Longitudinal Analysis of
      Clinical and Quality-of-life Measures.
AB  - BACKGROUND: Lyme disease is the most common vector-borne disease in the United
      States. Some patients report persistent or intermittent subjective symptoms of
      mild to moderate intensity after antibiotic treatment for Lyme disease. We sought
      to evaluate trends in clinical and quality-of-life (QOL) measures in a cohort of
      patients with Lyme disease enrolled in a natural history study at the National
      Institutes of Health from 2001-2014. METHODS: QOL was measured using the self
      administered 36-item Short Form Health Survey (SF-36) during study follow-up.
      Primary outcomes included mean physical (PCS) and mental (MCS) health QOL
      composite scores and reporting long-term (>=2 years) symptoms, adjusted for Lyme
      disease stage and severity at diagnosis. RESULTS: Overall, 101 patients with an
      average follow-up time of 3.9 years (range, 0.5-11.3 years) were included. At
      first visit, overall mean QOL scores were below the US population mean for both
      PCS (45.6 +/- 10.4) and MCS (47.3 +/- 11.5) but increased to just above the
      national average after 3 years of follow-up for both PCS (50.7 +/- 9.6) and MCS
      (50.1 +/- 10.0). Baseline QOL scores were lowest in those with late disease (P <
      0.01) but also increased by the end of follow-up to national averages. In
      multivariate analysis, the only factors significantly associated with long-term
      symptoms or lower QOL scores were other comorbidities unrelated to Lyme disease.
      CONCLUSIONS: Comorbid conditions can play a role in the reporting of long-term
      symptoms and overall QOL of Lyme disease patients and should be considered in the
      evaluation of these patients. CLINICAL TRIALS REGISTRATION: NCT00028080.

PMID- 27025826
TI  - Beyond Antibiotics: New Therapeutic Approaches for Bacterial Infections.
AB  - The utility of conventional antibiotics for the treatment of bacterial infections
      has become increasingly strained due to increased rates of resistance coupled
      with reduced rates of development of new agents. As a result, multidrug
      resistant, extensively drug-resistant, and pandrug-resistant bacterial strains
      are now frequently encountered. This has led to fears of a "postantibiotic era"
      in which many bacterial infections will be untreatable. Alternative nonantibiotic
      treatment strategies need to be explored to ensure that a robust pipeline of
      effective therapies is available to clinicians. In this review, we highlight some
      of the recent developments in this area, such as the targeting of bacterial
      virulence factors, utilization of bacteriophages to kill bacteria, and
      manipulation of the microbiome to combat infections.

PMID- 27025827
TI  - Editorial Commentary: The Dawning of Microbiome Remediation for Addressing
      Antibiotic Resistance.

PMID- 27025829
TI  - A Randomized Trial of Clindamycin Versus Trimethoprim-sulfamethoxazole for
      Uncomplicated Wound Infection.
AB  - BACKGROUND: With the emergence of community-associated methicillin-resistant
      Staphylococcus aureus (MRSA) in the United States, visits for skin infections
      greatly increased. Staphylococci and streptococci are considered predominant
      causes of wound infections. Clindamycin and trimethoprim-sulfamethoxazole (TMP
      SMX) are commonly prescribed, but the efficacy of TMP-SMX has been questioned.
      METHODS: We conducted a randomized, double-blind, superiority trial at 5 US
      emergency departments. Patients >12 years of age with an uncomplicated wound
      infection received oral clindamycin 300 mg 4 times daily or TMP-SMX 320 mg/1600
      mg twice daily, each for 7 days. We compared the primary outcome, wound infection
      cure at 7-14 days, and secondary outcomes through 6-8 weeks after treatment, in
      the per-protocol population. RESULTS: Subjects had a median age of 40 years
      (range, 14-76 years); 40.1% of wound specimens grew MRSA, 25.7% methicillin
      susceptible S. aureus, and 5.0% streptococci. The wound infection was cured at 7
      14 days in 187 of 203 (92.1%) clindamycin-treated and 182 of 198 (91.9%) TMP-SMX
      treated subjects (difference, 0.2%; 95% confidence interval [CI], -5.8% to 6.2%;
      P = not significant). The clindamycin group had a significantly lower rate of
      recurrence at 7-14 days (1.5% vs 6.6%; difference, -5.1%; 95% CI, -9.4% to -.8%)
      and through 6-8 weeks following treatment (2.0% vs 7.1%; difference, -5.1%; 95%
      CI, -9.7% to -.6%). Other secondary outcomes were statistically similar between
      groups but tended to favor clindamycin. Adverse event rates were similar.
      CONCLUSIONS: In settings where MRSA is prevalent, clindamycin and TMP-SMX produce
      similar cure and adverse event rates among patients with an uncomplicated wound
      infection. Further study evaluating differential effects of antibiotics on
      recurrent infection may be warranted. CLINICAL TRIALS REGISTRATION: NCT00729937.

PMID- 27025830
TI  - Reply to Verhaeghe et al.

PMID- 27025828
TI  - Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy
      Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment:
      Collaborative Cohort Study.
AB  - BACKGROUND: CD4 count at start of combination antiretroviral therapy (ART) is
      strongly associated with short-term survival, but its association with longer
      term survival is less well characterized. METHODS: We estimated mortality rates
      (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and >=10
      years) among patients from 18 European and North American cohorts who started ART
      during 1996-2001. Piecewise exponential models stratified by cohort were used to
      estimate crude and adjusted (for sex, age, transmission risk, period of starting
      ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus
      type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART
      (0-49, 50-99, 100-199, 200-349, 350-499, >=500 cells/uL) overall and separately
      according to time since start of ART. RESULTS: A total of 6344 of 37 496 patients
      died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8
      (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to
      16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10
      years' duration of ART. During the first year of ART, there was a strong inverse
      association of CD4 count at start of ART with mortality. This diminished over the
      next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P =
      .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and
      >=10 years, respectively. CONCLUSIONS: After surviving 5 years of ART, the
      mortality of patients who started ART with low baseline CD4 count converged with
      mortality of patients with intermediate and high baseline CD4 counts.

PMID- 27025831
TI  - Environmental Contamination and Viral Shedding in MERS Patients.

PMID- 27025832
TI  - Disparities in HIV Care Along the Path From Infection to Viral Suppression: A
      Cross-sectional Study of HIV/AIDS Patient Records in 2013, Shandong Province,
      China.
AB  - BACKGROUND: The 90-90-90 targets recommended by the Joint United Nations
      Programme on HIV/AIDS require strengthening human immunodeficiency virus (HIV)
      care, which includes diagnosis, linkage to and retention in care, assessment for
      treatment suitability, and optimization of HIV treatment. We sought to quantify
      patient engagement along the continuum, 10 years after introduction of Chinese
      HIV care policies. METHODS: We included patients from Shandong, China, who were
      diagnosed with HIV from 1992 to 2013. Records were obtained from the HIV/AIDS
      Comprehensive Response Information Management System to populate a 7-step HIV
      care continuum. Pearson chi(2) test and multivariate logistic regression were
      used for analysis. RESULTS: Of 6500 estimated HIV-infected persons, 60.1% were
      diagnosed, of whom 41.9% received highly active antiretroviral therapy (HAART).
      Only 59.6% of patients on HAART and 15% of all infected persons achieved viral
      suppression. Children infected by mother-to-child transmission (MTCT) and persons
      infected by intravenous drug use were less likely to be linked to and retained in
      care (odds ratio [OR], 0.33 [95% confidence interval {CI}, .14-.80] and OR, 0.58
      [95% CI, .40-.90], respectively). Persons tested in custodial institutions were
      substantially less likely to be on HAART (OR, 0.22 [95% CI, .09-.59]) compared
      with those tested in medical facilities. Patients on HAART infected by homosexual
      or heterosexual transmission and those infected by MTCT were less likely to
      achieve viral suppression (OR, 0.18 [95% CI, .09-.34]; OR, 0.12 [95% CI, .06
      .22]; OR, 0.07 [95% CI, .02-.20], respectively). CONCLUSIONS: Our report
      suggests, at the current rate, Shandong Province has to accelerate HIV care
      efforts to close disparities in HIV care and achieve the 90-90-90 goals
      equitably.

PMID- 27025833
TI  - Identifying Meningitis During an Anthrax Mass Casualty Incident: Systematic
      Review of Systemic Anthrax Since 1880.
AB  - BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a potential
      bioterrorism agent. Anthrax meningitis is a common manifestation of B. anthracis
      infection, has high mortality, and requires more aggressive treatment than
      anthrax without meningitis. Its rapid identification and treatment are essential
      for successful management of an anthrax mass casualty incident. METHODS: Three
      hundred six published reports from 1880 through 2013 met predefined inclusion
      criteria. We calculated descriptive statistics for abstracted cases and conducted
      multivariable regression on separate derivation and validation cohorts to
      identify clinical diagnostic and prognostic factors for anthrax meningitis.
      RESULTS: One hundred thirty-two of 363 (36%) cases with systemic anthrax met
      anthrax meningitis criteria. Severe headache, altered mental status, meningeal
      signs, and other neurological signs at presentation independently predicted
      meningitis in the derivation cohort and were tested as a 4-item assessment tool
      for use during anthrax mass casualty incidents. Presence of any 1 factor on
      admission had a sensitivity for finding anthrax meningitis of 89% (83%) in the
      adult (pediatric) validation cohorts. Anthrax meningitis was unlikely in the
      absence of any of these signs or symptoms (likelihood ratio [LR]- = 0.12 [0.19]
      for adult [pediatric] cohorts), while presence of 2 or more made meningitis very
      likely (LR+ = 26.5 [30.0]). Survival of anthrax meningitis was predicted by
      treatment with a bactericidal agent (P = .005) and use of multiple antimicrobials
      (P = .01). CONCLUSIONS: We developed an evidence-based assessment tool for
      screening patients for meningitis during an anthrax mass casualty incident. Its
      use could improve both patient outcomes and resource allocation in such an event.

PMID- 27025834
TI  - The Pandemic H30 Subclone of Escherichia coli Sequence Type 131 Is Associated
      With Persistent Infections and Adverse Outcomes Independent From Its Multidrug
      Resistance and Associations With Compromised Hosts.
AB  - BACKGROUND: The H30 subclone within Escherichia coli sequence type 131 (ST131
      H30) has emerged rapidly to become the leading antibiotic-resistant E. coli
      strain. Hypervirulence, multidrug resistance, and opportunism have been proposed
      as explanations for its epidemic success. METHODS: We assessed 1133 consecutive
      unique E. coli clinical isolates from 5 medical centers (2010-2011) for H30
      genotype, which we compared with epidemiological and clinical data extracted from
      medical records by blinded reviewers. Using univariable and multivariable
      logistic regression analysis, we explored associations of H30 with underlying
      host characteristics, clinical presentations, management, and outcomes, adjusting
      for host characteristics. RESULTS: The H30 (n = 107) isolates were associated
      with hosts who were older, male, locally and systemically compromised, and
      healthcare and antibiotic exposed. With multivariable adjustment for host
      factors, H30 lost its numerous significant univariable associations with initial
      clinical presentation, but remained strongly associated with clinical persistence
      (odds ratio [OR], 3.47; 95% confidence interval [CI], 1.89-6.37), microbiological
      persistence (OR, 4.46; 95% CI, 2.38-8.38), subsequent hospital admission (OR,
      2.68; 95% CI, 1.35-5.33), and subsequent new infection (OR, 1.73; 95% CI, 1.01
      3.00). These host-adjusted associations remained strong even with added
      adjustment for resistance to the initially prescribed antibiotics, and the
      adverse outcome associations (subsequent hospital admission, new infection) were
      independent of clinical and microbiological persistence. CONCLUSIONS: In addition
      to targeting compromised hosts and resisting multiple antibiotics, H30 isolates
      may have an intrinsic ability to cause highly persistent infections and later
      adverse outcomes. The basis for these host- and resistance-independent
      associations is unclear, but they should be considered when managing patients
      with H30 infections.

PMID- 27025835
TI  - 12 Weeks of Daclatasvir in Combination With Sofosbuvir for HIV-HCV Coinfection
      (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens.
AB  - BACKGROUND: Highly effective hepatitis C virus (HCV) direct-acting antiviral
      therapies that do not require modification of human immunodeficiency virus (HIV)
      antiretroviral regimens are needed. We evaluated the efficacy and safety of
      daclatasvir + sofosbuvir (DCV + SOF) for 12 weeks by antiretroviral (ARV) regimen
      in HIV-HCV-coinfected patients. METHODS: In the randomized, open-label ALLY-2
      study, HIV-HCV-coinfected patients received 8 or 12 weeks of once-daily DCV 60 mg
      (dose-adjusted as-necessary for concomitant ARVs) + SOF 400 mg. Results were
      stratified by ARV class for the 151 patients who received 12 weeks of DCV + SOF.
      RESULTS: Fifty-one patients were HCV treatment experienced, 100 were treatment
      naive, 89% male and 33% black. HCV genotypes were: genotype 1a (GT1a; 69%), GT1b
      (15%), GT2 (8%), GT3 (6%), and GT4 (2%). Sustained virologic response 12 weeks
      post-treatment (SVR12) was 97% and was similar across ARV regimens (P = .774):
      protease inhibitor-based, 97% (95% confidence interval [CI], 90%-99.7%);
      nonnucleoside reverse transcriptase inhibitor-based, 100% (95% CI, 91%-100%); and
      integrase inhibitor based, 95% (95% CI, 83%-99.4%). SVR12 among patients
      receiving either tenofovir disoproxil fumarate or abacavir as part of their
      antiretroviral therapy regimen was 98% (95% CI, 93%-99.5%) and 100% (95% CI, 85%
      100%), respectively. Age, gender, race, cirrhosis, HCV treatment history, GT ,
      and baseline HCV RNA did not affect SVR12. No discontinuations were attributed to
      treatment-related adverse events. CONCLUSIONS: DCV + SOF x12 weeks is a highly
      efficacious, all-oral, pan-GT HCV treatment for HIV-HCV coinfected patients
      across a broad range of ARV regimens. CLINICAL TRIALS REGISTRATION: NCT02032888.

PMID- 27025836
TI  - Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With
      Recurrent Clostridium difficile Infection.
AB  - BACKGROUND: Recurrent Clostridium difficile infection (RCDI) is associated with
      repeated antibiotic treatment and the enhanced growth of antibiotic-resistant
      microbes. This study tested the hypothesis that patients with RCDI would harbor
      large numbers of antibiotic-resistant microbes and that fecal microbiota
      transplantation (FMT) would reduce the number of antibiotic-resistant genes.
      METHODS: In a single center study, patients with RCDI (n = 20) received FMT from
      universal donors via colonoscopy. Stool samples were collected from donors (n =
      3) and patients prior to and following FMT. DNA was extracted and shotgun
      metagenomics performed. Results as well as assembled libraries from a healthy
      cohort (n = 87) obtained from the Human Microbiome Project were aligned against
      the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance
      Database. Results were corroborated through a DNA microarray containing 354
      antibiotic resistance (ABR) genes. RESULTS: RCDI patients had a greater number
      and diversity of ABR genes compared with donors and healthy controls. Beta
      lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR
      genes were increased in RCDI patients, although donors primarily had tetracycline
      resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli
      and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that
      correlated directly with a decreased number and diversity of ABR genes and
      increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene
      profiles were maintained in recipients for up to a year following FMT.
      CONCLUSIONS: RCDI patients have increased numbers of antibiotic-resistant
      organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant
      organisms and elimination of ABR genes.

PMID- 27025837
TI  - Cough Aerosols of Mycobacterium tuberculosis in the Prediction of Incident
      Tuberculosis Disease in Household Contacts.
AB  - BACKGROUND: Tuberculosis disease develops in only 5%-10% of humans infected with
      Mycobacterium tuberculosis The mechanisms underlying this variability remain
      poorly understood. We recently demonstrated that colony-forming units of M.
      tuberculosis in cough-generated aerosols are a better predictor of infection than
      the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol
      cultures may also predict progression to tuberculosis disease in contacts.
      METHODS: We conducted a retrospective cohort study of 85 patients with smear
      positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index
      case patients underwent a standard evaluation, and we cultured M. tuberculosis
      from cough aerosols. Contacts underwent a standard evaluation at enrollment, and
      they were later traced to determine their tuberculosis status. RESULTS: During a
      median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis
      disease. In unadjusted and adjusted analyses, incident tuberculosis disease in
      contacts was associated with sputum Mycobacterial Growth Indicator Tube culture
      (odds ratio, 8.2; 95% confidence interval, 1.1-59.2; P = .04), exposure to a high
      aerosol tuberculosis case patient (6.0, 1.4-25.2; P = .01), and marginally, human
      immunodeficiency virus in the contact (6.11; 0.89-41.7; P = .07). We present data
      demonstrating that sputum and aerosol specimens measure 2 related but different
      phenomena. CONCLUSIONS: We found an increased risk of tuberculosis progression
      among contacts of high-aerosol case patients. The hypothesis that a larger
      infectious inoculum, represented by high aerosol production, determines the risk
      of disease progression deserves evaluation in future prospective studies.

PMID- 27025838
TI  - A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low
      Influenza Vaccine Effectiveness During the 2014-2015 Season.
AB  - BACKGROUND: The 2014-2015 influenza season was distinguished by an epidemic of
      antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013
      2014. We report 2014-2015 vaccine effectiveness (VE) from Canada and explore
      contributing agent-host factors. METHODS: VE against laboratory-confirmed
      influenza was derived using a test-negative design among outpatients with
      influenza-like illness. Sequencing identified amino acid mutations at key
      antigenic sites of the viral hemagglutinin protein. RESULTS: Overall, 815/1930
      (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%)
      influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577;
      99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460
      (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations
      F159Y (a cluster-transition position) and K160T (a predicted gain of
      glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2)
      was -17% (95% confidence interval [CI], -50% to 9%) overall with clade-specific
      VE of -13% (95% CI, -51% to 15%) for clade 3C.2a but 52% (95% CI, -17% to 80%)
      for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients
      vaccinated in 2014-2015 only, significantly lower at -32% (95% CI, -75% to 0%) if
      also vaccinated in 2013-2014 and -54% (95% CI, -108% to -14%) if vaccinated each
      year since 2012-2013. VE against clade-mismatched B(Yamagata) viruses was 42%
      (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination
      compared to A(H3N2). CONCLUSIONS: Variation in the viral genome and negative
      effects of serial vaccination likely contributed to poor influenza vaccine
      performance in 2014-2015.

PMID- 27025839
TI  - Reply to Oh.

PMID- 27025840
TI  - Academic pediatric clinical research: factors associated with study
      implementation duration.
AB  - BACKGROUND: The ethical, methodological, and technical aspects of pediatric
      research, often results in complications and delays in implementation. Our
      objective was to identify factors associated with the implementation duration of
      hospital-based pediatric studies. METHODS: All hospital-based pediatric studies
      sponsored by AP-HP between 2002 and 2008 were retrospectively identified.
      Association of the funding mechanism and methodological factors with the
      implementation duration was assessed using a multivariable mixed linear model.
      Pharmaceutical factors were explored as part of a subgroup analysis restricted to
      the studies involving drug therapy. Given that we took an exploratory approach,
      factors associated with implementation duration with p < 0.10 were kept in the
      final models. RESULTS: A total of 139 studies were evaluated. The median
      implementation duration was 17.1 months (range: 0.9-55.3 months), and tended to
      increase over time (from 14.9 [25(th) percentile-75(th) percentile: 11.5-19.9]
      months in 2002 to 23.7 [15.2-31.0] months in 2008, p = 0.01). External
      (coefficient [95 % confidence interval]: -7.7 [-11.9;-3.5] months, p < 0.001) and
      internal funding (-5.3 95 % CI [-9.8;-0.8], p = 0.02) compared to governmental
      funding and number of centers (-0.1 95 % CI[-0.2;0.02] months for 1 center
      increase, p = 0.07) were associated with reduced duration, whereas interventional
      study (either involving drug therapy (6.0 95 % CI[0.7;11.3] months, p = 0.03 or
      not (3.5 95 % CI[-0.3;7.3] months, p = 0.06) was associated with increased
      duration compared to observational study. Regarding the 35 studies involving drug
      therapy, external funding decreased duration (-6.7 95 % CI[-13.2;-0.2] months, p
      = 0.05), whereas studies involving solely a pediatric population (7.8 95 %
      CI[1.1;14.5] months, p = 0.01) (compared to mixed adult-pediatric population), a
      placebo-controlled design (6.6 95 % CI[0.9;12.3] months, p = 0.01), and
      inappropriate drug formulation for at least one drug used in the study (6.9 95 %
      CI[-0.2;14.0] months, p = 0.06) were associated with increased duration.
      CONCLUSION: Implementation of hospital-based pediatric studies primarily faced
      delays when they were interventional and, in particular, when they involved drug
      therapy. Regarding the latter, difficulties that resulted in delayed studies
      arose with respect to the supply of drugs and placebo in age-appropriate dosages
      and route of administration. Therefore, difficulties related to the use of
      pharmaceuticals need to be anticipated earlier in order to avoid implementation
      delays.

PMID- 27025841
TI  - Evaluation of the risk factors associated with rectal neuroendocrine tumors: a
      big data analytic study from a health screening center.
AB  - BACKGROUND: Rectal neuroendocrine tumor (NET) is the most common NET in Asia. The
      risk factors associated with rectal NETs are unclear because of the overall low
      incidence rate of these tumors and the associated difficulty in conducting large
      epidemiological studies on rare cases. The aim of this study was to exploit the
      benefits of big data analytics to assess the risk factors associated with rectal
      NET. METHODS: A retrospective case-control study was conducted, including 102
      patients with histologically confirmed rectal NETs and 52,583 healthy controls
      who underwent screening colonoscopy at the Center for Health Promotion of the
      Samsung Medical Center in Korea between January 2002 and December 2012.
      Information on different risk factors was collected and logistic regression
      analysis applied to identify predictive factors. RESULTS: Four factors were
      significantly associated with rectal NET: higher levels of cholesterol [odds
      ratio (OR) = 1.007, 95 % confidence interval (CI), 1.001-1.013, p = 0.016] and
      ferritin (OR = 1.502, 95 % CI, 1.167-1.935, p = 0.002), presence of metabolic
      syndrome (OR = 1.768, 95 % CI, 1.071-2.918, p = 0.026), and family history of
      cancer among first-degree relatives (OR = 1.664, 95 % CI, 1.019-2.718, p =
      0.042). CONCLUSION: The findings of our study demonstrate the benefits of using
      big data analytics for research and clinical risk factor studies. Specifically,
      in this study, this analytical method was applied to identify higher levels of
      serum cholesterol and ferritin, metabolic syndrome, and family history of cancer
      as factors that may explain the increasing incidence and prevalence of rectal
      NET.

PMID- 27025842
TI  - Single-CpG resolution mapping of 5-hydroxymethylcytosine by chemical labeling and
      exonuclease digestion identifies evolutionarily unconserved CpGs as TET targets.
AB  - Conventional techniques for single-base resolution mapping of epigenetic
      modifications of DNA such as 5-hydroxymethylcytosine (5hmC) rely on the
      sequencing of bisulfite-modified DNA. Here we present an alternative approach
      called SCL-exo which combines selective chemical labeling (SCL) of 5hmC in
      genomic DNA with exonuclease (exo) digestion of the bead-trapped modified DNA
      molecules. Associated with a straightforward bioinformatic analysis, this new
      procedure provides an unbiased and fast method for mapping this epigenetic mark
      at high resolution. Implemented on mouse genomic DNA from in vitro-differentiated
      neural precursor cells, SCL-exo sheds light on an intrinsic lack of conservation
      of hydroxymethylated CpGs across vertebrates.

PMID- 27025843
TI  - Aminophylline and caffeine for reversal of adverse symptoms associated with
      regadenoson SPECT MPI.
AB  - BACKGROUND: Aminophylline shortages led us to compare intravenous (IV)
      aminophylline with IV and oral (PO) caffeine during routine pharmacologic stress
      testing with SPECT MPI. METHODS: We measured presence, duration, and reversal of
      adverse symptoms and cardiac events following regadenoson administration in
      consecutive patients randomized to IV aminophylline (100 mg administered over 30
      60 seconds), IV caffeine citrate (60 mg infused over 3-5 minutes), or PO caffeine
      as coffee or diet cola. RESULTS: Of 241 patients, 152 (63%) received regadenoson
      reversal intervention. Complete (CR), predominant (PRE), or partial (PR) reversal
      was observed in 99%. CR by IV aminophylline (87%), IV caffeine (87%), and PO
      caffeine (78%) were similar (P = NS). Time to CR (162 +/- 12.6 seconds, mean +/-
      SD) was similar in treatment arms. PO caffeine was inferior to IV aminophylline
      for CR + PRE. CONCLUSIONS: IV aminophylline and IV caffeine provide rapid, safe
      reversal of regadenoson-induced adverse effects during SPECT MPI. Oral caffeine
      appeared similarly effective for CR but not for the combined CR + PRE. Our
      results suggest PO caffeine may be an effective initial strategy for reversal of
      regadenoson, but IV aminophylline or IV caffeine should be available to optimize
      symptom reversal as needed.

PMID- 27025845
TI  - Myocardial ischemia in the absence of obstructive coronary lesion: The role of
      post-stress diastolic dysfunction in detecting early coronary atherosclerosis.
AB  - BACKGROUND: The interactions between non-obstructive coronary atherosclerosis
      (<50% stenosis) and myocardial perfusion and functional parameters on myocardial
      perfusion imaging (MPI) have never been evaluated. METHODS AND RESULTS: One
      hundred and ninety-five patients were submitted to stress-rest MPI and invasive
      coronary angiography. The presence of obstructive coronary lesions (>50%
      stenosis) was excluded. The summed stress score (SSS) was calculated in every
      patient. Moreover, the left ventricular (LV) ejection fraction (EF) and peak
      filling rate (PFR) were computed from gated MPI images as measures of systolic
      and diastolic functions. Sixty/195 patients (31%) showed the presence of non
      obstructive atherosclerosis (>20% and <50% diameter reduction). Interestingly,
      they presented a higher SSS than those with normal coronary arteries (P < 0.001)
      despite a similar myocardial scar burden. If compared to patients with normal
      coronary arteries, those with non-obstructive atherosclerosis showed more
      abnormal post-stress PFR values (2.5 +/- 0.9 vs 2.9 +/- 0.8, P = 0.004), despite
      a similar EF. On multivariate analysis, the presence non-obstructive
      atherosclerosis was the only significant predictor (P = 0.026) of post-stress LV
      diastolic impairment, independently from perfusion parameters. CONCLUSIONS: In
      patients without anatomically significant coronary lesions, the development of
      post-stress LV diastolic dysfunction on MPI associates with the presence of non
      obstructive atherosclerosis on coronary angiography.

PMID- 27025846
TI  - Predictors of Hospitalization in Patients With Transient Ischemic Attack or Minor
      Ischemic Stroke.
AB  - BACKGROUND: Transient ischemic attack (TIA) and minor stroke are associated with
      a substantial risk of subsequent stroke; however, there is uncertainty about
      whether such patients require admission to hospital for their initial management.
      We used data from a clinical stroke registry to determine the frequency and
      predictors of hospitalization for TIA or minor stroke across the province of
      Ontario, Canada. METHODS: The Ontario Stroke Registry collects information on a
      population-based sample of all patients seen in the emergency department with
      acute stroke or TIA in Ontario. We identified patients with minor ischemic stroke
      or TIA included in the registry between April 1, 2008, and March 31, 2011, and
      used multivariable analyses to evaluate predictors of hospitalization. RESULTS:
      Our study sample included 8540 patients with minor ischemic stroke or TIA, 47.2%
      of whom were admitted to hospital, with a range of 37.6% to 70.3% across
      Ontario's 14 local health integration network regions. Key predictors of
      admission were preadmission disability, vascular risk factors, presentation with
      weakness, speech disturbance or prolonged/persistent symptoms, arrival by
      ambulance, and presentation on a weekend or during periods of emergency
      department overcrowding. CONCLUSIONS: More than one-half of patients with minor
      stroke or TIA were not admitted to the hospital, and there were wide regional
      variations in admission patterns. Additional work is needed to provide guidance
      to health care workers around when to admit such patients and to determine
      whether discharged patients are receiving appropriate follow-up care.

PMID- 27025847
TI  - More Challenges in Measuring Care Quality.

PMID- 27025848
TI  - Factors influencing the variation in GMS prescribing expenditure in Ireland.
AB  - BACKGROUND: Pharmaceutical expenditure growth is a familiar feature in many
      Western health systems and is a real concern for policymakers. A state funded
      General Medical Services (GMS) scheme in Ireland experienced an increase in
      prescription expenditure of 414 % between 1998 and 2012. This paper seeks to
      explore the rationale for this growth by investigating the composition
      (Anatomical Therapeutic Chemical (ATC) Group level 1 & 5) and drivers of GMS drug
      expenditure in Ireland in 2012. METHODS: A cross-sectional study was carried out
      on the Health Service Executive-Primary Care Reimbursement Service (HSE-PCRS)
      population prescribing database (n = 1,630,775). Three models were applied to
      test the association between annual expenditure per claimant whilst controlling
      for age, sex, region, and the pharmacology of the drugs as represented by the
      main ATC groups. RESULTS: The mean annual cost per claimant was ?751 (median =
      ?211; SD = ?1323.10; range = ?3.27-?298,670). Age, sex, and regions were all
      significant contributory factors of expenditure, with gender having the greatest
      impact (beta = 0.107). Those aged over 75 (beta =1.195) were the greatest
      contributors to annual GMS prescribing costs. As regards regions, the South has
      the greatest cost increasing impact. When the ATC groups were included the impact
      of gender is diluted by the pharmacology of the products, with cardiovascular
      prescribing (ATC 'C') most influential (beta = 1.229) and the explanatory power
      of the model increased from 40 % to 60 %. CONCLUSION: Whilst policies aimed at
      cost containment (co-payment charges; generic substitution; reference pricing;
      adjustments to GMS eligibility) can be used to curtail expenditure, health
      promotional programs and educational interventions should be given equal
      emphasis. Also policies intended to affect physicians' prescribing behaviour
      include guidelines, information (about price and less expensive alternatives) and
      feedback, and the use of budgetary restrictions could yield savings in Ireland
      and can be easily translated to the international context.

PMID- 27025849
TI  - Living cumulative network meta-analysis to reduce waste in research: A
      paradigmatic shift for systematic reviews?
AB  - In a recent research article in BMC Medicine, Crequit and colleagues demonstrate
      how published systematic reviews in lung cancer provide a fragmented, out-of-date
      picture of the evidence for all treatments. The results and conclusions drawn
      from this study, based on cumulative network meta-analyses (NMA) of evidence from
      randomized clinical trials over time, are quite compelling. The inherent waste of
      research resulting from incomplete evidence synthesis has wide-reaching
      implications for a range of target groups including developers of systematic
      reviews and guidelines and their end-users, health care professionals and
      patients at the point of care. Building on emerging concepts for living
      systematic reviews and NMA, the authors propose "living cumulative NMA" as a
      potential solution and paradigmatic shift. Here we describe how recent
      innovations within authoring, dissemination, and updating of systematic reviews
      and trustworthy guidelines may greatly facilitate the production of living NMA.
      Some additional challenges need to be solved for NMA in general, and for living
      cumulative NMA in particular, before a paradigmatic shift for systematic reviews
      can become reality.Please see related research article:
      https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0555-0. 

PMID- 27025850
TI  - Deglycosylation of Tropheryma whipplei biofilm and discrepancies between
      diagnostic results during Whipple's disease progression.
AB  - Whipple's disease is a systemic infectious disease associated with the bacterium
      Tropheryma whipplei. Numerous reports have presented puzzling discrepancies
      between diagnosis methods. We addressed this confusion using fluorescent in situ
      hybridization and immunofluorescence assays to evaluate 34 duodenal biopsies and
      1 lymph node biopsy from Whipple's patients. We showed the presence of bacteria
      in both CK20(+) epithelial cells and CD68(+) macrophages. Bacteria are found
      embedded in a biofilm hindering the detection of T. whipplei. Only after
      treatment of biopsies by glycosidases, co-localization of T. whipplei RNA/DNA
      with bacterial proteins was restored. Moreover, using 13 bronchoalveolar lavages
      and 7 duodenal biopsies, we found that hydrolysis of the biofilm weakened the
      bacteria, facilitated bacterial DNA extraction and improved the sensitivity of
      qPCR detection by up to 1000x opening new perspectives for diagnostic and
      scientific approaches. 

PMID- 27025852
TI  - Triple trouble: a striking new phenotype or competing genes in a family with
      hereditary spastic paraplegia.

PMID- 27025853
TI  - N-methyl-D-aspartate receptor encephalitis mediates loss of intrinsic activity
      measured by functional MRI.
AB  - Spontaneous brain activity is required for the development and maintenance of
      normal brain function. Many disease processes disrupt the organization of
      intrinsic brain activity, but few pervasively reduce the amplitude of resting
      state blood oxygen level dependent (BOLD) fMRI fluctuations. We report the case
      of a female with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis,
      longitudinally studied during the course of her illness to determine the
      contribution of NMDAR signaling to spontaneous brain activity. Resting state BOLD
      fMRI was measured at the height of her illness and 18 weeks following discharge
      from hospital. Conventional resting state networks were defined using established
      methods. Correlation and covariance matrices were calculated by extracting the
      BOLD time series from regions of interest and calculating either the correlation
      or covariance quantity. The intrinsic activity was compared between visits, and
      to expected activity from 45 similarly aged healthy individuals. Near the height
      of the illness, the patient exhibited profound loss of consciousness, high
      amplitude slowing of the electroencephalogram, and a severe reduction in the
      amplitude of spontaneous BOLD fMRI fluctuations. The patient's neurological
      status and measures of intrinsic activity improved following treatment. We
      conclude that NMDAR-mediated signaling plays a critical role in the mechanisms
      that give rise to organized spontaneous brain activity. Loss of intrinsic
      activity is associated with profound disruptions of consciousness and cognition. 

PMID- 27025854
TI  - Inhibition of SOCs Attenuates Acute Lung Injury Induced by Severe Acute
      Pancreatitis in Rats and PMVECs Injury Induced by Lipopolysaccharide.
AB  - Acute lung injury (ALI) is a critical complication of the severe acute
      pancreatitis (SAP), characterized by increased pulmonary permeability with high
      mortality. Pulmonary microvascular endothelial cells (PMVECs) injury and
      apoptosis play a key role in ALI. Previous studies indicated that store-operated
      calcium entry (SOCE) could regulate a variety of cellular processes. The present
      study was to investigate the effects of SOCE inhibition on ALI induced by SAP in
      Sprague-Dawley rats, and PMVECs injury induced by lipopolysaccharide (LPS). Rat
      model of SAP-associated ALI were established by the retrograde infusion of sodium
      deoxycholate. Serum levels of amylase, TNF-alpha, and IL-6, histological changes,
      water content of the lung, oxygenation index, and ultrastructural changes of
      PMVECs were examined in ALI rats with or without store-operated Ca(2+) channels
      (SOCs) pharmacological inhibitor (2-aminoethoxydiphenyl borate, 2-APB)
      pretreatment. For in vitro studies, PMVECs were transiently transfected with or
      without small interfering RNA (siRNA) against calcium release-activated calcium
      channel protein1 (Orai1) and stromal interaction molecule1 (STIM1), the two main
      molecular constituents of SOCs, then exposed to LPS. The viability of PMVECs was
      determined. The expression of STIM1, Orai1, Bax, and caspase3, both in lung
      tissue and in PMVECs, were assessed by quantitative real-time PCR and western
      blot. Administration of sodium deoxycholate upregulated the expression of SOCs
      proteins in lung tissue. Similarly, the SOCs proteins were increased in PMVECs
      induced by LPS. 2-APB reduced the serum levels of amylase, TNF-alpha, and IL-6,
      and attenuated lung water content and histological findings. In addition, the
      decreased oxygenation index and ultrastructural damage in PMVECs associated with
      SAP were ameliorated after administration of 2-APB. Knockdown of STIM1 and Orai1
      inhibited LPS-induced PMVECs death. Furthermore, blockade of SOCE significantly
      suppressed Orai1, STIM1, Bax, and caspase3 expression both in vivo and in vitro.
      These results suggest that SOCE may play a critical role in SAP-associated ALI
      and the protective effects of inhibition of SOCs could be mediated, at least
      partially, by restraining mitochondrial associated apoptosis of PMVECs. 

PMID- 27025855
TI  - Studies of Influenza A/H1N1 A/Tomsk/13/2010 Virus Topology during Development of
      Infectious Process in Mammals.
AB  - Influenza A/H1N1 A/Tomsk/13/2010 virus registered in Siberia in 2010 proved to be
      an extremely pathogenic strain. Dynamic study of the topology of this influenza
      virus strain in the lungs, liver, kidneys, lymph nodes, and great vessels of
      infected mice was carried out. Influenza A virus was detected by
      immunohistochemical methods in cells of different histogenesis in all the studied
      organs throughout the observation period (days 1-30 postinfection), which
      indicated effective replication and long persistence of influenza A/H1N1
      A/Tomsk/13/2010 virus in mammalian cells. 

PMID- 27025851
TI  - Recent advances in amyotrophic lateral sclerosis.
AB  - ALS is a relentlessly progressive and fatal disease, with no curative therapies
      available to date. Symptomatic and palliative care, provided in a
      multidisciplinary context, still remains the cornerstone of ALS management.
      However, our understanding of the molecular mechanisms underlying the disease has
      advanced greatly over the past years, giving new hope for the development of
      novel diagnostic and therapeutic approaches. Here, we have reviewed the most
      recent studies that have contributed to improving both clinical management and
      our understanding of ALS pathogenesis. 

PMID- 27025856
TI  - Progress of targeted genome modification approaches in higher plants.
AB  - Transgene integration in plants is based on illegitimate recombination between
      non-homologous sequences. The low control of integration site and number of
      (trans/cis)gene copies might have negative consequences on the expression of
      transferred genes and their insertion within endogenous coding sequences. The
      first experiments conducted to use precise homologous recombination for gene
      integration commenced soon after the first demonstration that transgenic plants
      could be produced. Modern transgene targeting categories used in plant biology
      are: (a) homologous recombination-dependent gene targeting; (b) recombinase
      mediated site-specific gene integration; (c) oligonucleotide-directed
      mutagenesis; (d) nuclease-mediated site-specific genome modifications. New tools
      enable precise gene replacement or stacking with exogenous sequences and targeted
      mutagenesis of endogeneous sequences. The possibility to engineer chimeric
      designer nucleases, which are able to target virtually any genomic site, and use
      them for inducing double-strand breaks in host DNA create new opportunities for
      both applied plant breeding and functional genomics. CRISPR is the most recent
      technology available for precise genome editing. Its rapid adoption in biological
      research is based on its inherent simplicity and efficacy. Its utilization,
      however, depends on available sequence information, especially for genome-wide
      analysis. We will review the approaches used for genome modification,
      specifically those for affecting gene integration and modification in higher
      plants. For each approach, the advantages and limitations will be noted. We also
      will speculate on how their actual commercial development and implementation in
      plant breeding will be affected by governmental regulations. 

PMID- 27025857
TI  - Radiotherapy plus concomitant temozolomide in primary gliosarcoma.
AB  - Clinical guidelines for gliosarcoma (GSM) are poorly defined and GSM patients are
      usually treated in accordance with existing guidelines for glioblastoma (GBM),
      with maximal surgical resection followed by chemoradiation with temozolomide
      (TMZ). However, it is not clear yet if GSM patients profit from TMZ therapy and
      if O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is crucial.
      We retrospectively evaluated 37 patients with histologically proven, primary GSM
      who had received radiation therapy since the temozolomide era (post-2005). Twenty
      five patients (67.6 %) received combined chemoradiation with temozolomide, and 12
      cases (32.4 %) received radiation therapy alone. Molecular markers were
      determined retrospectively. Survival and correlations were calculated using log
      rank, univariate, and multivariate Cox proportional hazards-ratio analyses. All
      cases were isocitrate dehydrogenase 1 (IDH1) wildtype, MGMT promoter methylation
      could be observed in 33.3 % of the assessable cases (10/30) and TERT promoter
      mutation was seen in a high frequency of 86.7 % (26/30). The influence of TMZ
      therapy on overall survival (OS) was significantly improved compared with cases
      in which radiation therapy alone was performed (13.9 vs. 9.9 months; p = 0.045),
      independently of MGMT promoter methylation. The positive effect of TMZ on OS was
      confirmed in this study's multivariate analyses (p = 0.04), after adjusting our
      results for potential confounders. In conclusion, this study demonstrates that
      concomitant TMZ together with radiation therapy increases GSM-patient survival
      independent of MGMT promoter methylation. Thus, GSM can be treated in accordance
      to GBM guidelines. MGMT promoter methylation was infrequent and TERT promoter
      mutation common without influencing the survival rates. The mechanisms of TMZ
      effects in GSM are still not fully understood and merit further clinical and
      molecular-genetic and -biological evaluation.

PMID- 27025858
TI  - Pattern of relapse of glioblastoma multiforme treated with radical radio
      chemotherapy: Could a margin reduction be proposed?
AB  - To analyse the pattern of recurrence of patients treated with Stupp protocol in
      relation to technique, to compare in silico plans with reduced margin (1 cm) with
      the original ones and to analyse toxicity. 105 patients were treated: 85 had
      local recurrence and 68 of them were analysed. Recurrence was considered in
      field, marginal and distant if >80 %, 20-80 % or <20 % of the relapse volume was
      included in the 95 %-isodose. In silico plans were retrospectively recalculated
      using the same technique, fields angles and treatment planning system of the
      original ones. The pattern of recurrence was in field, marginal and distant in
      88, 10 and 2 % respectively and was similar in in silico plans. The margin
      reduction appears to spare 100 cc of healthy brain by 57 Gy-volume (p = 0.02).
      The target coverage was worse in standard plans (pt student < 0.001), especially
      if the tumour was near to organs at risk (pchi2 < 0.001). PTV coverage was better
      with IMRT and helical-IMRT, than conformal-3D (pAnova test = 0.038). This
      difference was no more significant with in silico planning. A higher incidence of
      asthenia and leuko-encephalopathy was observed in patients with greater
      percentage of healthy brain included in 57 Gy-volume. No differences in the
      pattern of recurrence according to margins were found. The margin reduction
      determines sparing of healthy brain and could possibly reduce the incidence of
      late toxicity. Margin reduction could allow to use less sophisticated techniques,
      ensuring appropriate target coverage, and the choice of more costly techniques
      could be reserved to selected cases.

PMID- 27025859
TI  - Morphology, proliferation, and gene expression of gingival fibroblasts on Laser
      Lok, titanium, and zirconia surfaces.
AB  - Soft tissue seal plays a critical role in long-term success of dental implants,
      and the effects of implant surface treatments such as laser ablation have been a
      topic of particular interest in this respect. Considering the existing
      controversy regarding soft tissue behavior in contact with implant surfaces, this
      study sought to assess the morphology, proliferation, and gene expression of
      human gingival fibroblasts (HGFs) on different abutment surfaces. In this in
      vitro, experimental study, HGFs were cultured on 45 discs (Laser-Lok, titanium,
      and zirconia). Cell morphology, proliferation rate, and interleukin 10 (IL-10),
      tumor necrosis factor alpha (TNFalpha), fibronectin, and integrin gene
      expressions were assessed by electron microscopy, methyl thiazol tetrazolium
      (MTT) assay, and real-time polymerase chain reaction (PCR), respectively. Data
      were analyzed using ANOVA and the Kruskal-Wallis H test. Fibroblast attachment
      was noted in all the three groups. Spindle-shaped cells with pseudopod-like
      processes were more frequently seen in the Laser-Lok group. Cell proliferation
      was significantly higher in the Laser-Lok group compared to those in the other
      groups (P = 0.0002). Significant differences were found in the expression of IL
      10, TNFalpha, fibronectin, and integrin genes among the groups (P < 0.01). Within
      the limitations of this study, HGFs on Laser-Lok surfaces had a more mature
      morphology and greater proliferation and differentiation as compared to those on
      zirconia and titanium surfaces. This indicates better attachment of these cells
      to laser-modified surfaces, creating a more efficient soft tissue seal around
      dental implants. 

PMID- 27025860
TI  - Efficacy of laser therapy in the management of bisphosphonate-related
      osteonecrosis of the jaw (BRONJ): a systematic review.
AB  - Bisphosphonate-related osteonecrosis of the jaw is a well-known potential side
      effect of long-term bisphosphonate therapy; the primary objective of the
      treatment should be to improve patient quality of life through pain and infection
      management, to prevent the development of new lesions, and to slow disease
      progression. In recent years, the use of laser for bisphosphonate-related
      osteonecrosis of the jaw has become more widespread, due to its use of
      administration and widely reported beneficial effects on tissue healing. The
      present systematic review of the literature sought to elucidate whether low-level
      laser therapy has positive effects on the treatment of bisphosphonate-related
      osteonecrosis of the jaw. We conducted a systematic search of the PubMed, EMBASE,
      and Cochrane Library electronic databases, with no restrictions on language or
      year of publication. Search strategies were formulated using keywords and Boolean
      operators. The electronic search strategy retrieved 55 records. From 55 articles,
      16 were selected for full-text review, and of these, 10 were ultimately included
      for data analysis in this review. Our findings show that treatment modalities
      including laser were associated with superior outcomes in terms of cure or
      improvement of bisphosphonate-related osteonecrosis of the jaw lesions as
      compared with conventional surgical and/or conservative drug therapy. It can be
      concluded that combined treatment with antibiotics, minimally invasive surgery
      (including Er:YAG laser surgery), and low-level laser therapy in the early stages
      of the disease should be the gold standard for bisphosphonate-related
      osteonecrosis of the jaw management. 

PMID- 27025862
TI  - Challenges and Paradoxes of Human Factors in Health Technology Design.
AB  - Usability testing allows human factors professionals to identify and mitigate
      issues with the design and use of medical technology. The test results, however,
      can be paradoxical and therefore be misinterpreted, limiting their usefulness.
      The paradoxical findings can lead to products that are not aligned with the needs
      and constraints of their users. We herein report on our observations of the
      paradox of expertise, the paradox of preference versus performance, and the
      paradox of choice. Each paradox explored is in the perspective of the design of
      medical technology, the issues that need to be considered in the interpretation
      of the test results, as well as suggestions on how to avoid the pitfalls in the
      design of medical technology. Because these paradoxes can influence product
      design at various stages of product development, it is important to be aware of
      the effects to interpret the findings properly. 

PMID- 27025863
TI  - How to treat ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      Key practical messages from the 2015 American College of Rheumatology
      recommendations.
AB  - A panel of experts commissioned by the American College of Rheumatology have
      recently reviewed the literature related to the treatment of patients with
      ankylosing spondylitis and nonradiographic axial spondyloarthritis. They
      published a set of recommendations for the management of common clinical
      questions for both active and stable disease, including the appropriate use of
      nonsteroidal anti-inflammatory drugs, tumor necrosis factor inhibitors,
      rehabilitation, education, and preventive care. This article summarizes these
      recommendations and provides key practical messages for physicians taking care of
      these patients.

PMID- 27025864
TI  - A new optical coupling control technique and application in SWL.
AB  - The objective of this study was to compare the results of shock wave lithotripsy
      (SWL) between patients treated with optical coupling control (OCC) and those
      treated with "blind" coupling during SWL to treat renal stones. Enrolled in the
      study were patients with urinary stones who underwent SWL between January 2014
      and February 2015. The lithotripter used in the study was an electromagnetic
      Dornier Compact Delta II UIMS. The closed envelope method was used to randomize
      the enroled patients to OCC (Group A) or "Blind" coupling group (Group B). The
      stone-free rates (SFRs) were determined using KUB film with or without
      ultrasonography after 3 months. Treatment failure was defined as radiologically
      confirmed persistence of the stone with no fragmentation after second SWL
      sessions. Complications during the intraoperative or post-operative periods were
      recorded. A total of 336 patients satisfied the inclusion criteria for the study,
      of which 169 patients were treated in the Group A and 167 in the Group B. There
      was no significant difference in patient and stone characteristics between the
      two groups (Table 1). The locations of treated stones are shown in Table 2. The
      treatment results were stratified by stone location in Table 3, significant
      differences existed in all treatment results between the two groups (P < 0.05).
      The overall stone-free rates after 3 months were 78.2 % for kidney stones and
      81.7 % for ureteral stones in patients from Group A. The corresponding SFRs for
      patients in Group B were 62.8 and 67.9 % for stones in the kidneys and ureters,
      respectively. There were statistical differences in these results between the two
      groups (P < 0.05). The lithotripter with OCC had excellent shock wave
      transmission properties with the least possible loss of energy; it can lead to
      the optimization of SWL treatment outcome and reduce the incidence of SW-induced
      adverse effects. We are confident that the OCC used in this study should be a
      standard feature in future lithotripters. Table 1 Patients' and stones'
      characteristics Group A Group B P value Number of patients 169 167 Patients'
      gender (M/F) 97/72 109/58 0.138 Stone location (left/right) 86/83 89/78 0.659
      Patients' age (years) 36.3 +/- 7.1 34.2 +/- 6.8 0.521 Size of stones  Kidney (cm)
      1.4 +/- 0.6 1.3 +/- 0.7 0.452  Ureter (cm) 1.1 +/- 0.5 1.1 +/- 0.4 0.354  Average
      size (cm) 1.2 +/- 0.8 1.2 +/- 0.7 0.372 Table 2 The distribution of location of
      stones treated Group A % Group B % Upper calyx 21 12.4 25 15.0 Middle calyx 28
      16.6 23 13.8 Lower calyx 7 4.1 5 3.0 Renal pelvis 31 18.3 33 19.8 Upper ureter 28
      16.6 31 18.6 Middle ureter 6 3.6 4 2.4 Lower ureter 48 28.4 46 27.5 Overall 169
      100.0 167 100.0 Table 3 The treatment results were stratified by stone location
      Group A Group B %Stone-free %Re-treatment %Ancillary procedure %Stone-free %Re
      treatment %Ancillary procedure Kidney  Upper calyx 76.2 33.3 14.3 60.0 48.0 12.0 
      Middle calyx 75.0 35.7 7.1 56.5 56.5 13.0  Lower calyx 71.4 42.9 28.6 60.0 60.0
      40.0  Renal pelvis 83.9 29.0 9.7 69.7 45.5 12.1  Overall 78.2 33.3 11.5 62.8 50.
      0 14.0 Ureter  Upper ureter 82.1 28.6 10.7 74.2 32.3 16.1  Middle ureter 66.7
      66.7 33.3 50. 75.0 50.0  Lower ureter 83.3 25.0 10.4 65.0 41.3 13.0  Overall 81.7
      29.3 12.2 67.9 39.5 16.0.

PMID- 27025861
TI  - The Inflammatory Response in Psoriasis: a Comprehensive Review.
AB  - Psoriasis is a chronic inflammatory autoimmune disease characterized by an
      excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of
      psoriasis is complex and the exact mechanism remains elusive. However, psoriasis
      is thought to result from a combination of genetic, epigenetic, and environmental
      influences. Recent studies have identified that epigenetic factors including
      dysregulated DNA methylation levels, abnormal histone modification and microRNAs
      expressions are involved in the development of psoriasis. The interplay of immune
      cells and cytokines is another critical factor in the pathogenesis of psoriasis.
      These factors or pathways include Th1/Th2 homeostasis, the Th17/Treg balance and
      the IL-23/Th17 axis. Th17 is believed particularly important in psoriasis due to
      its pro-inflammatory effects and its involvement in an integrated inflammatory
      loop with dendritic cells and keratinocytes, contributing to an overproduction of
      antimicrobial peptides, inflammatory cytokines, and chemokines that leads to
      amplification of the immune response. In addition, other pathways and signaling
      molecules have been found to be involved, including Th9, Th22, regulatory T
      cells, gammadelta T cells, CD8(+) T cells, and their related cytokines.
      Understanding the pathogenesis of psoriasis will allow us to develop increasingly
      efficient targeted treatment by blocking relevant inflammatory signaling pathways
      and molecules. There is no cure for psoriasis at the present time, and much of
      the treatment involves managing the symptoms. The biologics, while lacking the
      adverse effects associated with some of the traditional medications such as
      corticosteroids and methotrexate, have their own set of side effects, which may
      include reactivation of latent infections. Significant challenges remain in
      developing safe and efficacious novel targeted therapies that depend on a better
      understanding of the immunological dysfunction in psoriasis. 

PMID- 27025865
TI  - Hypoglycaemia in cystic fibrosis in the absence of diabetes: A systematic review.
AB  - BACKGROUND: Hypoglycaemia in CF in the absence of diabetes or glucose lowering
      therapies is a phenomenon that is receiving growing attention in the literature.
      These episodes are sometimes symptomatic and likely have variable aetiologies.
      Our first aim was to conduct a systematic review of the literature to determine
      what is known about hypoglycaemia in CF. Our second aim was to assess evidence
      based guidelines for management strategies. METHODS: A comprehensive search of
      databases and guideline compiler entities was performed. Inclusion criteria were
      primary research articles and evidence based guidelines that referred to
      hypoglycaemia in CF in the absence of insulin treatment or other glucose lowering
      therapies. RESULTS: A total of 11 studies (four manuscripts and seven abstracts)
      and five evidence-based guidelines met the inclusion criteria. Prevalence rates
      of hypoglycaemia unrelated to diabetes varied between studies (7-69%).
      Hypoglycaemia was diagnosed during oral glucose tolerance testing or continuous
      glucose monitoring (CGM). Associations between hypoglycaemia and clinical
      parameters of BMI, lung function, liver disease and pancreatic insufficiency were
      measured in some studies. There was no unifying definition of hypoglycaemia in
      the absence of diabetes. Only two evidence based guidelines reported possible
      management strategies. CONCLUSION: The systematic review found limited data on
      this clinical problem and supports the need for high quality methodological
      studies that are able to describe the experience and the aetiology(ies) of
      hypoglycaemia in CF.

PMID- 27025866
TI  - Towards microfluidic sperm refinement: impedance-based analysis and sorting of
      sperm cells.
AB  - The use of high quality semen for artificial insemination in the livestock
      industry is essential for successful outcome. Insemination using semen with a
      high number of sperm cells containing morphological defects has a negative impact
      on fertilization outcome. Therefore, semen with a high number of these abnormal
      cells is discarded in order to maintain high fertilization potential, resulting
      in the loss of a large number of morphologically normal sperm cells (up to 70-80%
      of original sample). A commonly occurring morphological sperm anomaly is the
      cytoplasmic droplet on the sperm flagella. Currently, no techniques are available
      to extract morphologically normal sperm cells from rejected samples. Therefore,
      we aim to develop a microfluidic setup which is able to detect and sort
      morphologically normal sperm cells label-free and non-invasively. In a proof-of
      concept experiment, differential impedance measurements were used to detect the
      presence of cytoplasmic droplets on sperm flagella, which was quantified by
      calculating the area under the curve (AUC) of the corresponding impedance peaks.
      A receiver operating characteristic curve of this electrical analysis method
      showed the good predictive power of this analysis method (AUC value of 0.85).
      Furthermore, we developed a label-free cell sorting system using LabVIEW, which
      is capable of sorting sperm cells based on impedance. In a proof-of-concept
      experiment, sperm cells and 3 MUm beads were sorted label-free and non-invasively
      using impedance detection and dielectrophoresis sorting. These experiments
      present our first attempt to perform sperm refinement using microfluidic
      technology. 

PMID- 27025867
TI  - [Evolution of total knee arthroplasty. From robotics and navigation to patient
      specific instruments].
AB  - In this article the evolution beginning with the robotics of total knee
      arthroplasty to CT-based and kinematic navigation and patient-specific
      instruments is described. Thereby it is pointed out that in the early 1990s, CT
      imaging solely for the planning of a knee endoprosthesis was considered as
      obsolete radiation exposure and this led to the widespread development of
      kinematical systems.Also a patient specific planning tool based on CAD built
      acryl harz blocs existed at the time. There is an ongoing process of implanting
      total knee arthroplasties in a more exact position. Nowadays the new evolution of
      soft tissue balancing by using a kinematic alignment has put these efforts into
      perspective. 

PMID- 27025868
TI  - [The MyKnee(r) patient-specific system. Rationale, Technique and Results].
AB  - BACKGROUND: Adequate three-dimensional component positioning and restoration of
      overall limb alignment are primary goals in total knee arthroplasty. Patient
      specific instrumentation (PSI) is a potential way to improve accuracy of knee
      reconstruction surgery. However, currently available literature regarding the
      reliability of PSI shows inconsistent results for limb alignment restoration and
      component positioning. OBJECTIVES: The purpose of this article is to illustrate
      the rationale for using PSI in total knee arthroplasty, to demonstrate the
      surgical technique, and to present our outcome with the MyKnee((r)) system.
      METHODS: We illustrate in detail the logistics and workflow involved in PSI for
      total knee arthroplasty. Finally, we present clinical and radiological results of
      patients undergoing knee arthroplasty using the MyKnee((r)) system compared to a
      conventional instrumentation group. RESULTS: PSI significantly improved accuracy
      and reduced the number of outliers regarding neutral mechanical alignment
      restoration as well as three-dimensional component positioning compared to
      conventional instrumentation. The early clinical outcome was comparable between
      the two instrumentation groups. However, clinical outcome in the subgroup of
      patients within +/- 3 degrees  from neutral mechanical limb alignment was
      superior to limb alignment outliers. CONCLUSION: The MyKnee((r)) PSI system
      presents a reliable way to improve the accuracy of mechanical limb alignment
      restoration and three-dimensional component positioning in total knee
      arthroplasty. Nonetheless, an adequate surgical technique remains the crucial
      factor for successful total knee reconstruction.

PMID- 27025869
TI  - [Total and unicompartmental knee replacement. Patient-specific Instrumentation].
AB  - BACKGROUND: The objective of patient-specific instrumentation (PSI Zimmer(r))
      technology is to optimize positioning and selection of components as well as
      surgical procedure in uni- and bicompartimental knee replacement. The article
      contains a description of the planning and surgical technique and evaluates the
      method based on own results and literature. METHODS: Using MRI or CT scans a
      virtual 3D model of the joint is created in order to simulate and plan the
      implant positioning. According to these data, pin placement and/or cutting guides
      are produced, which enable the surgeon to transfer the planning to the surgical
      procedure. In a prospective comparative study 88 patients (44 per each of the two
      techniques) were operated by one surgeon receiving the same TKA using either MRI
      based PSI or a conventional technique. The number of surgical trays, operating
      time, intraoperative changes and frontal alignment using a full leg x-ray (70
      cases) were compared. In 17 patients the method was applied with unicondylar knee
      replacement. RESULTS: Anatomical abnormalities could be detected preoperatively
      and considered during the operation. With PSI the number of trays could be
      reduced and predictability of the component size was more precise. Intraoperative
      changes became necessary only for distal femoral (25 %) and proximal tibial (36
      %) resection and tibial rotation (40 %). Alignment was more precise in the PSI
      cases DISCUSSION: PSI using the applied technique proved to be practicable and
      reliable. The advantages of precise planning became obvious. Results concerning
      alignment are inconsistent in the literature. Soft tissue balancing has only been
      included in the technique to a limited degree so far. PSI is still in an early
      stage of development and further development opportunities should be exploited
      before final assessment.

PMID- 27025870
TI  - [Total knee arthroplasty. Patient-specific instruments and implants].
AB  - This article describes the concept and surgical technique of patient-specific
      total knee arthroplasty. Patient-specific implants and instruments are designed
      and fabricated based on computed tomography (CT) data of the leg. The disposable
      patient-specific drill guides and cutting-jigs are manufactured taking into
      consideration the anatomical and biomechanical axes of the knee joint and
      mediating the efficient pre-navigation of the osseous saw-cuts, without the need
      for additional navigation or balancing aids. The surgical plan is made on the
      basis of the CT data. The implantation technique comprises the following steps:
      distal femoral resection, tibial resection, balancing and femur preparation,
      tibia preparation, optional patellar resurfacing, trialling of the test
      components, and implantation of the final components. By using this patient
      specific implant system, which includes not only personalized, single-use
      instruments, but also individualized implants, the surgeon is able to provide
      endoprosthetic treatment that broadly restores the patient's own knee anatomy and
      knee kinematics. Preliminary studies have proven the concept and data on this
      technology are promising so far; however, like a new implant, they are usually
      limited. In particular, comparative long-term clinical data are still to come. 

PMID- 27025871
TI  - Effects of gender role self-discrepancies and self-perceived attractiveness on
      social anxiety for women across social situations.
AB  - BACKGROUND AND OBJECTIVES: Psychosocial factors, such as gender role norms, may
      impact how social anxiety disorder (SAD) is experienced and expressed in
      different social contexts for women. However to date, these factors have not been
      examined via experimental methodology. DESIGN: This was a cross-sectional, quasi
      experimental controlled study. METHODS: The current study included 48 highly
      socially anxious (HSA) women (70.9% meeting criteria for SAD) and examined the
      relationships among psychosocial factors (i.e. gender role self-discrepancies and
      self-perceived physical attractiveness), self-perceived social performance, and
      state anxiety, across two in vivo social tasks (i.e. conversation and opinion
      speech). RESULTS: On average, participants reported belief that they ought to be
      less feminine for the speech task and more masculine for both the conversation
      and speech tasks. Also, for the conversation task, only lower self-rated
      attractiveness predicted poorer self-perceived performance and greater post-task
      state anxiety, above gender role self-discrepancies and confederate gender. For
      the speech task, only greater self-discrepancy in prototypical masculine traits
      predicted poorer performance ratings, and it was related to greater state anxiety
      in anticipation of the task. CONCLUSION: For HSA women, psychosocial factors may
      play different roles in social anxiety across social contexts.

PMID- 27025872
TI  - The Aldo-Keto Reductase AKR1B10 Is Up-Regulated in Keloid Epidermis, Implicating
      Retinoic Acid Pathway Dysregulation in the Pathogenesis of Keloid Disease.
AB  - Keloid disease is a recurrent fibroproliferative cutaneous tumor of unknown
      pathogenesis for which clinical management remains unsatisfactory. To obtain new
      insights into hitherto underappreciated aspects of keloid pathobiology, we took a
      laser capture microdissection-based, whole-genome microarray analysis approach to
      identify distinct keloid disease-associated gene expression patterns within
      defined keloid regions. Identification of the aldo-keto reductase enzyme AKR1B10
      as highly up-regulated in keloid epidermis suggested that an imbalance of
      retinoic acid metabolism is likely associated with keloid disease. Here, we show
      that AKR1B10 transfection into normal human keratinocytes reproduced the abnormal
      retinoic acid pathway expression pattern we had identified in keloid epidermis.
      Cotransfection of AKR1B10 with a luciferase reporter plasmid showed reduced
      retinoic acid response element activity, supporting the hypothesis of retinoic
      acid synthesis deficiency in keloid epidermis. Paracrine signals released by
      AKR1B10-overexpressing keratinocytes into conditioned medium resulted in up
      regulation of transforming growth factor-beta1, transforming growth factor-beta2,
      and collagens I and III in both keloid and normal skin fibroblasts, mimicking the
      typical profibrotic keloid profile. Our study results suggest that insufficient
      retinoic acid synthesis by keloid epidermal keratinocytes may contribute to the
      pathogenesis of keloid disease. We refocus attention on the role of injured
      epithelium in keloid disease and identify AKR1B10 as a potential new target in
      future management of keloid disease.

PMID- 27025873
TI  - Combinatorial microenvironmental regulation of liver progenitor differentiation
      by Notch ligands, TGFbeta, and extracellular matrix.
AB  - The bipotential differentiation of liver progenitor cells underlies liver
      development and bile duct formation as well as liver regeneration and disease.
      TGFbeta and Notch signaling are known to play important roles in the liver
      progenitor specification process and tissue morphogenesis. However, the
      complexity of these signaling pathways and their currently undefined interactions
      with other microenvironmental factors, including extracellular matrix (ECM),
      remain barriers to complete mechanistic understanding. Utilizing a series of
      strategies, including co-cultures and cellular microarrays, we identified
      distinct contributions of different Notch ligands and ECM proteins in the fate
      decisions of bipotential mouse embryonic liver (BMEL) progenitor cells. In
      particular, we demonstrated a cooperative influence of Jagged-1 and TGFbeta1 on
      cholangiocytic differentiation. We established ECM-specific effects using
      cellular microarrays consisting of 32 distinct combinations of collagen I,
      collagen III, collagen IV, fibronectin, and laminin. In addition, we demonstrated
      that exogenous Jagged-1, Delta-like 1, and Delta-like 4 within the cellular
      microarray format was sufficient for enhancing cholangiocytic differentiation.
      Further, by combining Notch ligand microarrays with shRNA-based knockdown of
      Notch ligands, we systematically examined the effects of both cell-extrinsic and
      cell-intrinsic ligand. Our results highlight the importance of divergent Notch
      ligand function and combinatorial microenvironmental regulation in liver
      progenitor fate specification. 

PMID- 27025874
TI  - Metabolic Syndrome and Periodontal Disease Progression in Men.
AB  - Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular
      disease, is associated with periodontal disease, but few studies have been
      prospective in design. This study's aim was to determine whether metabolic
      syndrome predicts tooth loss and worsening of periodontal disease in a cohort of
      760 men in the Department of Veterans Affairs Dental Longitudinal Study and
      Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic
      and diastolic blood pressures were measured with a standard mercury
      sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a
      normal expiration. Fasting blood samples were measured in duplicate for glucose,
      triglyceride, and high-density lipoprotein. Calibrated periodontists served as
      dental examiners. Periodontal outcome events on each tooth were defined as
      progression to predefined threshold levels of probing pocket depth (>=5 mm),
      clinical attachment loss (>=5 mm), mobility (>=0.5 mm), and alveolar bone loss
      (>=40% of the distance from the cementoenamel junction to the root apex, on
      radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a
      periodontitis event were estimated from tooth-level extended Cox proportional
      hazards regression models that accounted for clustering of teeth within
      individuals and used time-dependent status of metabolic syndrome. Covariates
      included age, education, smoking status, plaque level, and initial level of the
      appropriate periodontal disease measure. Metabolic syndrome as defined by the
      International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08
      to 1.79), pocket depth >=5 mm (1.37; 1.14 to 1.65), clinical attachment loss >=5
      mm (1.19; 1.00 to 1.41), alveolar bone loss >=40% (1.25; 1.00 to 1.56), and tooth
      mobility >=0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome
      conditions was also associated with each of these outcomes. These findings
      suggest that the metabolic disturbances that comprise the metabolic syndrome may
      play a role in the development or worsening of periodontitis. 

PMID- 27025875
TI  - Leveraging signaling research to understand and treat disease.
AB  - This Editorial Guide describes an area of active signaling research. A challenge
      signaling researchers face is understanding how the information gained by
      analysis at the cellular and molecular levels can be translated to understanding
      higher-order organismal physiology and pathophysiology.

PMID- 27025878
TI  - PLIF: A rapid, accurate method to detect and quantitatively assess protein-lipid
      interactions.
AB  - Phosphoinositides are a type of cellular phospholipid that regulate signaling in
      a wide range of cellular and physiological processes through the interaction
      between their phosphorylated inositol head group and specific domains in various
      cytosolic proteins. These lipids also influence the activity of transmembrane
      proteins. Aberrant phosphoinositide signaling is associated with numerous
      diseases, including cancer, obesity, and diabetes. Thus, identifying
      phosphoinositide-binding partners and the aspects that define their specificity
      can direct drug development. However, current methods are costly, time-consuming,
      or technically challenging and inaccessible to many laboratories. We developed a
      method called PLIF (for "protein-lipid interaction by fluorescence") that uses
      fluorescently labeled liposomes and tethered, tagged proteins or peptides to
      enable fast and reliable determination of protein domain specificity for given
      phosphoinositides in a membrane environment. We validated PLIF against previously
      known phosphoinositide-binding partners for various proteins and obtained
      relative affinity profiles. Moreover, PLIF analysis of the sorting nexin (SNX)
      family revealed not only that SNXs bound most strongly to phosphatidylinositol 3
      phosphate (PtdIns3P or PI3P), which is known from analysis with other methods,
      but also that they interacted with other phosphoinositides, which had not
      previously been detected using other techniques. Different phosphoinositide
      partners, even those with relatively weak binding affinity, could account for the
      diverse functions of SNXs in vesicular trafficking and protein sorting. Because
      PLIF is sensitive, semiquantitative, and performed in a high-throughput manner,
      it may be used to screen for highly specific protein-lipid interaction
      inhibitors.

PMID- 27025876
TI  - Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA
      inhibition.
AB  - HSN2is a nervous system predominant exon of the gene encoding the kinase WNK1 and
      is mutated in an autosomal recessive, inherited form of congenital pain
      insensitivity. The HSN2-containing splice variant is referred to as WNK1/HSN2. We
      created a knockout mouse specifically lacking theHsn2exon ofWnk1 Although these
      mice had normal spinal neuron and peripheral sensory neuron morphology and
      distribution, the mice were less susceptible to hypersensitivity to cold and
      mechanical stimuli after peripheral nerve injury. In contrast, thermal and
      mechanical nociceptive responses were similar to control mice in an inflammation
      induced pain model. In the nerve injury model of neuropathic pain, WNK1/HSN2
      contributed to a maladaptive decrease in the activity of the K(+)-Cl(
      )cotransporter KCC2 by increasing its inhibitory phosphorylation at Thr(906)and
      Thr(1007), resulting in an associated loss of GABA (gamma-aminobutyric acid)
      mediated inhibition of spinal pain-transmitting nerves. Electrophysiological
      analysis showed that WNK1/HSN2 shifted the concentration of Cl(-)such that GABA
      signaling resulted in a less hyperpolarized state (increased neuronal activity)
      rather than a more hyperpolarized state (decreased neuronal activity) in mouse
      spinal nerves. Pharmacologically antagonizing WNK activity reduced cold allodynia
      and mechanical hyperalgesia, decreased KCC2 Thr(906)and Thr(1007)phosphorylation,
      and restored GABA-mediated inhibition (hyperpolarization) of injured spinal cord
      lamina II neurons. These data provide mechanistic insight into, and a compelling
      therapeutic target for treating, neuropathic pain after nerve injury.

PMID- 27025877
TI  - JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine
      kinase inhibitors.
AB  - Lung adenocarcinomas with mutant epidermal growth factor receptor (EGFR) respond
      to EGFR-targeted tyrosine kinase inhibitors (TKIs), but resistance invariably
      occurs. We found that the Janus kinase (JAK)/signal transduction and activator of
      transcription 3 (STAT3) signaling pathway was aberrantly increased in TKI
      resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells. JAK2 inhibition
      restored sensitivity to the EGFR inhibitor erlotinib in TKI-resistant cell lines
      and xenograft models of EGFR-mutant TKI-resistant lung cancer. JAK2 inhibition
      uncoupled EGFR from its negative regulator, suppressor of cytokine signaling 5
      (SOCS5), consequently increasing EGFR abundance and restoring the tumor cells'
      dependence on EGFR signaling. Furthermore, JAK2 inhibition led to
      heterodimerization of mutant and wild-type EGFR subunits, the activity of which
      was then blocked by TKIs. Our results reveal a mechanism whereby JAK2 inhibition
      overcomes acquired resistance to EGFR inhibitors and support the use of
      combination therapy with JAK and EGFR inhibitors for the treatment of EGFR
      dependent NSCLC.

PMID- 27025879
TI  - Evaluation of surgery risk factor associated to antithrombotic therapy in
      patients who underwent colorectal surgery.
AB  - BACKGROUND: Use of antiplatelet therapy in western people is common. The risk of
      bleeding related to surgical procedure or invasive procedure is higher.We want to
      analyse the correlation between colorectal surgery, antiplatelet therapy and
      postoperative surgical complications. METHODS: We categorized: 176 cases treated
      for colorectal cancer and we recorded the following data: type of surgery, body
      max index (BMI), haemoglobin value (Hb); preoperative prothrombin time (PT) and
      blood transfusions pre and postoperative and during surgery. The analysis focused
      on two groups: patients who received antiplatelet therapy (AT - antiplatelet
      therapy) and patients who didn't receive this therapy (NAT - not antiplatelet
      therapy). RESULTS: In the group of patients who underwent right emicolectomy,
      haemoglobin values were lower in patients who received antithrombotic therapy
      than in patients who didn't receive this therapy with a statistical significance
      (p < 0,05); the same datum resulted in patients who underwent left emicolectomy.
      Normal weight patients that received antiplatelet therapy had lower values of
      haemoglobin without statistical significance (p value not significant).
      Overweight patients who underwent therapy with antiplatelet agents had lesser Hb
      value than group that didn't performed this therapy (p < 0,05). Patients who
      received AT showed a bigger percentage of blood transfusions regardless of type
      of surgery than the second group with statistical significance Normal weight
      patients showed a different incidence of blood transfusions between patients who
      underwent antiplatelet therapy (50%) and patients who didn't receive this therapy
      (29%) with statistic significance (p < 0,05). Overweight patients didn't present
      this significant difference. We analyzed the incidence of post-operative
      complications in normal weight patients and overweight patients and we showed
      that the incidence of complications, both minor and major, was higher in patients
      who underwent antiplatelet therapy than in the second group regardless of weight
      CONCLUSIONS: Antiplatelet therapy in patients who underwent invasive surgery
      changes the incidence of some risk factors, such as bleeding, and of post
      operative complications. This result underlines the importance of careful
      handling and preparation in patients receiving antithrombotic agents that have to
      undergo invasive surgery. KEY WORDS: Antithrombotic therapy, Bleeding, Colorectal
      Surgery, Risk factor.

PMID- 27025880
TI  - Identifying strategies to increase influenza vaccination in GP practices: a
      positive deviance approach.
AB  - BACKGROUND: Influenza (flu) is an acute viral infection of the respiratory tract,
      which can lead to serious complications for individuals within at-risk groups.
      Evidence indicates that aspects of organization and delivery within GP practices
      can have an influence on the rates of flu vaccination uptake. Positive deviance
      is a methodological approach that facilitates identification of factors
      associated with high performance. OBJECTIVE: To use positive deviance to isolate
      factors associated with high performance by comparing GP practices achieving high
      and low flu vaccination uptake. METHODS: This was a qualitative study. A total of
      18 practice managers and 2 GPs from 20 GP practices participated, 10 with high
      and low vaccination rates, respectively. Telephone interviews were conducted,
      audio recorded and fully transcribed. Framework Analysis was used to analyse the
      data. RESULTS: High uptake practices were more likely than low uptake practices
      to have a lead member of staff who demonstrated tenacity, have aspirational
      uptake targets, have developed and used additional prompts within their IT
      systems to identify eligible patients, have GPs who were opportunistically
      vaccinating and use phone calls as a first-line strategy to invite patients for
      vaccination. CONCLUSIONS: This is the first known qualitative study to identify
      strategies used by UK GP practices to deliver seasonal flu vaccination
      programmes. It is one of few studies using the robust and novel approach of
      positive deviance to inform health care recommendations. This approach has
      offered new and more nuanced insights into GP practice factors associated high
      flu vaccination uptake beyond those captured through large-scale survey research.

PMID- 27025881
TI  - Diabetic Nephropathy: Focus on Current and Future Therapeutic Strategies.
AB  - BACKGROUND: Diabetic nephropathy (DN) is currently the most common cause of end
      stage renal disease (ESRD). Although nowadays much is known about its
      classification, pathogenesis, clinical manifestations and evolution, to date we
      are not yet able to stop the natural progression of nephropathy in diabetic
      patients. METHODS: Treatment options are: lifestyle change with close blood
      pressure monitoring and tight glycemic control. The most common therapies adopted
      for this condition are Angiotensing Converting Enzyme-inhibitors (ACEi). However
      these drugs are able to block the progression of renal damage only in a small
      proportion of patients. In the remaining, DN progresses and may evolve into ESRD.
      CONCLUSION: The purpose of this review is to summarize the "state of art" of
      current novel therapeutic strategies to stem this debilitating kidney disease.

PMID- 27025882
TI  - Parkinson's Disease: Recent Updates in the Identification of Human Dopa
      Decarboxylase Inhibitors.
AB  - Backround: Parkinson's disease is a pathology involving the progressive
      degeneration of dopaminergic neurons in the substantia nigra of the brain. L-DOPA
      combined with an inhibitor of DOPA decarboxylase, a pyridoxal 5'-phosphate
      dependent enzyme, is still the most effective treatment for symptoms of
      Parkinson's disease. LDOPA increases synaptic dopamine, while the inhibitor of
      peripheral DOPA decarboxylase reduces the conversion of L-DOPA to dopamine in the
      systemic circulation, allowing for greater L-DOPA distribution into the central
      nervous system. CarbiDOPA and benserazide are the inhibitors currently used in
      Parkinson's disease treatment. However, carbiDOPA and trihydroxybenzylhydrazine,
      the active metabolite of benserazide, are substrate analogues both endowed with a
      hydrazine function, which irreversibly bind not only to DDC but also to free
      pyridoxal 5'-phosphate and pyridoxal 5'-phosphate-dependent enzymes. Therefore,
      the lack of DOPA decarboxylase specificity, responsible for various side effects
      and adverse reactions, is a negative factor in such treatment of the disease.
      RESULTS AND CONCLUSION: Aim of this review is to report on the most recent
      investigations regarding new DOPA decarboxylase inhibitors that could represent
      the starting point for possible Parkinson's disease drugs development. We focused
      on the common chemical features among all the identified inhibitors in order to
      seek shared structural motifs that could be involved in inhibition. Then, we
      highlighted the extent of inhibition, measured by means of in vitro and/or cell
      based assays. Finally, we pointed out the state of the art in the metabolism of
      such classes of compounds, and discussed the possible advances in Parkinson's
      disease pharmacological treatment.

PMID- 27025883
TI  - Increased mortality associated with weekend hospital admission: a case for
      expanded seven day services?

PMID- 27025884
TI  - Microtubules, polarity and vertebrate neural tube morphogenesis.
AB  - Microtubules (MTs) are key cellular components, long known to participate in
      morphogenetic events that shape the developing embryo. However, the links between
      the cellular functions of MTs, their effects on cell shape and polarity, and
      their role in large-scale morphogenesis remain poorly understood. Here, these
      relationships were examined with respect to two strategies for generating the
      vertebrate neural tube: bending and closure of the mammalian neural plate; and
      cavitation of the teleost neural rod. The latter process has been compared with
      'secondary' neurulation that generates the caudal spinal cord in mammals. MTs
      align along the apico-basal axis of the mammalian neuroepithelium early in neural
      tube closure, participating functionally in interkinetic nuclear migration, which
      indirectly impacts on cell shape. Whether MTs play other functional roles in
      mammalian neurulation remains unclear. In the zebrafish, MTs are important for
      defining the neural rod midline prior to its cavitation, both by localizing
      apical proteins at the tissue midline and by orienting cell division through a
      mirror-symmetric MT apparatus that helps to further define the medial
      localization of apical polarity proteins. Par proteins have been implicated in
      centrosome positioning in neuroepithelia as well as in the control of polarized
      morphogenetic movements in the neural rod. Understanding of MT functions during
      early nervous system development has so far been limited, partly by techniques
      that fail to distinguish 'cause' from 'effect'. Future developments will likely
      rely on novel ways to selectively impair MT function in order to investigate the
      roles they play.

PMID- 27025885
TI  - Diastolic Left Ventricular Function in Relation to Circulating Metabolic
      Biomarkers in a General Population.
AB  - BACKGROUND: The metabolic signature associated with subclinical diastolic left
      ventricular (LV) dysfunction in the population remains ill defined. METHODS AND
      RESULTS: In 711 randomly recruited Flemish (50.8% women; mean age, 50.8 years),
      we assessed echocardiographic Doppler indexes of diastolic LV function in
      relation to 44 circulating metabolites determined by nuclear magnetic resonance
      spectroscopy. In multivariable-adjusted regression analysis with Bonferroni
      correction of significance levels applied, peak a' decreased (P<=0.048) and e'/a'
      increased (P<=0.044) with circulating tyrosine, high-density lipoprotein
      apolipoproteins, glucose+glutamine, and an unidentified molecule. Effect sizes
      expressed per 1-SD increment in the metabolite ranged from -0.277 to -0.203 cm/s
      for peak a' and from +0.047 to +0.054 for e'/a'. In addition, peak a' decreased
      (P<=0.031) with glucose+2-aminobutyrate (-0.261 cm/s) and glucose+2
      phosphoglycerate (-0.209 cm/s). In partial least square discriminant analysis
      (PLS-DA), metabolites associated with normal diastolic LV function (n=538)
      included glucose+glutamine, glucose+2-aminobutyrate, and glucose+2
      phosphoglycerate, whereas those siding with abnormal function encompassed 4
      aminobutyrate, 4-hydroxybutyrate, creatinine, and phosphocholine. In receiver
      operating characteristics plots, adding 3 latent factors identified by PLS-DA to
      prohormone brain natriuretic peptide increased (P<0.0001) the area under the
      curve from 0.64 (95% CI, 0.58-0.68) to 0.73 (0.68-0.78). CONCLUSIONS: In a
      general population, circulating metabolites indicative of energy substrate
      utilization and protection against oxidative stress differentiated normal from
      abnormal diastolic LV function. These findings improve our understanding of the
      pathophysiology underlying deterioration of diastolic LV function and potentially
      point to new targets for prevention and treatment of this condition.

PMID- 27025886
TI  - 5-Lipoxygenase Gene Variants Are Not Associated With Atherosclerosis or Incident
      Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis Cohort.
AB  - BACKGROUND: The arachidonate 5-lipoxygenase enzyme plays a crucial role in
      mediating inflammation to maintain homeostasis, yet certain allelic variants of
      the 5-lipoxygenase gene, ALOX5, may increase risk of atherosclerosis and coronary
      heart disease (CHD). Further, relations between ALOX5 and disease outcomes may be
      enhanced or attenuated depending on the bioavailability of 5-lipoxygenase enzyme
      substrates. By using a candidate gene approach in 6153 Multi-Ethnic Study of
      Atherosclerosis (MESA) participants, associations were determined among 1348
      ALOX5 single nucleotide polymorphisms (SNPs) and carotid intima-media thickness
      (cIMT) as well as incident CHD, and interactions with plasma concentrations of
      arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid were tested.
      METHODS AND RESULTS: Multivariable linear regression was used to test for
      associations between cIMT and ALOX5 SNPs, and Cox regression was used for
      incident CHD. Bonferroni correction was used for multiple hypothesis testing. No
      significant associations between ALOX5 SNPs and cIMT or CHD events were observed.
      Levels of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid
      concentrations did not modify the relations of ALOX5 with either outcome.
      CONCLUSIONS: ALOX5 gene variants do not appear to be related to clinical CHD
      events or subclinical atherosclerosis regardless of bioavailable enzyme substrate
      levels in this multiethnic cohort. Further studies that directly examine protein
      expression or enzyme activity may better define the arachidonate 5-lipoxygenase
      pathway in disease development and progression.

PMID- 27025888
TI  - [Not Available].

PMID- 27025894
TI  - Factoring attitudes towards armed conflict risk into selection of protected areas
      for conservation.
AB  - The high incidence of armed conflicts in biodiverse regions poses significant
      challenges in achieving international conservation targets. Because attitudes
      towards risk vary, we assessed different strategies for protected area planning
      that reflected alternative attitudes towards the risk of armed conflicts. We find
      that ignoring conflict risk will deliver the lowest return on investment. Opting
      to completely avoid conflict-prone areas offers limited improvements and could
      lead to species receiving no protection. Accounting for conflict by protecting
      additional areas to offset the impacts of armed conflicts would not only increase
      the return on investment (an effect that is enhanced when high-risk areas are
      excluded) but also increase upfront conservation costs. Our results also
      demonstrate that fine-scale estimations of conflict risk could enhance the cost
      effectiveness of investments. We conclude that achieving biodiversity targets in
      volatile regions will require greater initial investment and benefit from fine
      resolution estimates of conflict risk. 

PMID- 27025895
TI  - Hot Nanoparticles in Polar or Paramagnetic Liquids Interact as Monopoles.
AB  - When neutral nanoparticles are heated or cooled in a polar liquid, they will
      interact with each other as if they carry an electrostatic charge that is
      proportional to the temperature difference between the particle and the
      surrounding fluid. The same should hold for suspensions of asymmetric
      ferromagnetic particles, in which case the heated nanoparticles should behave as
      magnetic monopoles. However, the analogy with electrostatics/magnetostatics is
      not complete: heated/cooled nanoparticles do not move under the influence of an
      applied homogeneous field. They should, however, interact as monopoles with each
      other and should move in inhomogeneous fields.

PMID- 27025896
TI  - InformedTogether: Usability Evaluation of a Web-Based Decision Aid to Facilitate
      Shared Advance Care Planning for Severe Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Advance care planning may help patients receive treatments that
      better align with their goals for care. We developed a Web-based decision aid
      called InformedTogether to facilitate shared advance care planning between
      chronic obstructive pulmonary disease (COPD) patients and their doctors.
      OBJECTIVE: Our objective was to assess the usability of the InformedTogether
      decision aid, including whether users could interact with the decision aid to
      engage in tasks required for shared decision making, whether users found the
      decision aid acceptable, and implications for redesign. METHODS: We conducted an
      observational study with 15 patients and 8 doctors at two ethnically and
      socioeconomically diverse outpatient clinics. Data included quantitative and
      qualitative observations of patients and doctors using the decision aid on tablet
      or laptop computers and data from semistructured interviews. Patients were shown
      the decision aid by a researcher acting as the doctor. Pulmonary doctors were
      observed using the decision aid independently and asked to think aloud (ie,
      verbalize their thoughts). A thematic analysis was implemented to explore key
      issues related to decision aid usability. RESULTS: Although patients and doctors
      found InformedTogether acceptable and would recommend that doctors use the
      decision aid with COPD patients, many patients had difficulty understanding the
      icon arrays that were used to communicate estimated prognoses and could not
      articulate the definitions of the two treatment choices-Full Code and Do Not
      Resuscitate (DNR). Minor usability problems regarding content, links, layout, and
      consistency were also identified and corresponding recommendations were outlined.
      In particular, participants suggested including more information about potential
      changes in quality of life resulting from the alternative advance directives.
      Some doctor participants thought the decision aid was too long and some thought
      it may cause nervousness among patients due to the topic area. CONCLUSIONS: A
      decision aid for shared advance care planning for severe COPD was found
      acceptable to most COPD patients and their doctors. However, many patient
      participants did not demonstrate understanding of the treatment options or
      prognostic estimates. Many participants endorsed the use of the decision aid
      between doctors and their patients with COPD, although they desired more
      information about quality of life. The design must optimize comprehensibility,
      including revising the presentation of statistical information in the icon array,
      and feasibility of integration into clinical workflow, including shortening the
      decision aid.

PMID- 27025887
TI  - Plant Nitrogen Acquisition Under Low Availability: Regulation of Uptake and Root
      Architecture.
AB  - Nitrogen availability is a major factor determining plant growth and
      productivity. Plants acquire nitrogen nutrients from the soil through their roots
      mostly in the form of ammonium and nitrate. Since these nutrients are scarce in
      natural soils, plants have evolved adaptive responses to cope with the
      environment. One of the most important responses is the regulation of nitrogen
      acquisition efficiency. This review provides an update on the molecular
      determinants of two major drivers of the nitrogen acquisition efficiency: (i)
      uptake activity (e.g. high-affinity nitrogen transporters) and (ii) root
      architecture (e.g. low-nitrogen-availability-specific regulators of primary and
      lateral root growth). Major emphasis is laid on the regulation of these
      determinants by nitrogen supply at the transcriptional and post-transcriptional
      levels, which enables plants to optimize nitrogen acquisition efficiency under
      low nitrogen availability. 

PMID- 27025897
TI  - Assessing dose rate distributions in VMAT plans.
AB  - Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery
      techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic
      modulation of the dose rate, it is important to assess the changes in dose rate.
      Both the rate of monitor units per minute (MU rate) and collimation are varied
      over the course of a fraction, leading to different dose rates in every voxel of
      the calculation volume at any point in time during dose delivery. Given the
      radiotherapy plan and machine specific limitations, a VMAT treatment plan can be
      split into arc sectors between Digital Imaging and Communications in Medicine
      control points (CPs) of constant and known MU rate. By calculating dose
      distributions in each of these arc sectors independently and multiplying them
      with the MU rate, the dose rate in every single voxel at every time point during
      the fraction can be calculated. Independently calculated and then summed dose
      distributions per arc sector were compared to the whole arc dose calculation for
      validation. Dose measurements and video analysis were performed to validate the
      calculated datasets. A clinical head and neck, cranial and liver case were
      analyzed using the tool developed. Measurement validation of synthetic test cases
      showed linac agreement to precalculated arc sector times within +/-0.4 s and
      doses +/-0.1 MU (one standard deviation). Two methods for the visualization of
      dose rate datasets were developed: the first method plots a two-dimensional (2D)
      histogram of the number of voxels receiving a given dose rate over the course of
      the arc treatment delivery. In similarity to treatment planning system display of
      dose, the second method displays the dose rate as color wash on top of the
      corresponding computed tomography image, allowing the user to scroll through the
      variation over time. Examining clinical cases showed dose rates spread over a
      continuous spectrum, with mean dose rates hardly exceeding 100 cGy min(-1) for
      conventional fractionation. A tool to analyze dose rate distributions in VMAT
      plans with sub-second accuracy was successfully developed and validated. Dose
      rates encountered in clinical VMAT test cases show a continuous spectrum with a
      mean less than or near 100 cGy min(-1) for conventional fractionation.

PMID- 27025898
TI  - Direct hydrodeoxygenation of raw woody biomass into liquid alkanes.
AB  - Being the only sustainable source of organic carbon, biomass is playing an ever
      increasingly important role in our energy landscape. The conversion of renewable
      lignocellulosic biomass into liquid fuels is particularly attractive but
      extremely challenging due to the inertness and complexity of lignocellulose. Here
      we describe the direct hydrodeoxygenation of raw woods into liquid alkanes with
      mass yields up to 28.1 wt% over a multifunctional Pt/NbOPO4 catalyst in
      cyclohexane. The superior performance of this catalyst allows simultaneous
      conversion of cellulose, hemicellulose and, more significantly, lignin fractions
      in the wood sawdust into hexane, pentane and alkylcyclohexanes, respectively.
      Investigation on the molecular mechanism reveals that a synergistic effect
      between Pt, NbOx species and acidic sites promotes this highly efficient
      hydrodeoxygenation of bulk lignocellulose. No chemical pretreatment of the raw
      woody biomass or separation is required for this one-pot process, which opens a
      general and energy-efficient route for converting raw lignocellulose into
      valuable alkanes. 

PMID- 27025899
TI  - Analytical tools and protocols in oxidative stress.

PMID- 27025900
TI  - Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer
      therapies.
AB  - Utilization of thermal therapy (hyperthermia) is defined as the application of
      exogenous heat induction and represents a concept that is far from new as it goes
      back to ancient times when heat was used for treating various diseases, including
      malignancies. Such therapeutic strategy has gained even more popularity (over the
      last few decades) since various studies have shed light into understanding
      hyperthermia's underlying molecular mechanism(s) of action. In general,
      hyperthermia is applied as complementary (adjuvant) means in therapeutic
      protocols combining chemotherapy and/or irradiation both of which can induce
      irreversible cellular DNA damage. Furthermore, according to a number of in vitro,
      in vivo and clinical studies, hyperthermia has been shown to enhance the
      beneficial effects of DNA targeting therapeutic strategies by interfering with
      DNA repair response cascades. Therefore, the continuously growing evidence
      supporting hyperthermia's beneficial role in cancer treatment can also encourage
      its application as a DNA repair mitigation strategy. In this review article, we
      aim to provide detailed information on how hyperthermia acts on DNA damage and
      repair pathways and thus potentially contributing to various adjuvant therapeutic
      protocols relevant to more efficient cancer treatment strategies.

PMID- 27025902
TI  - Evaluation of Streptococcus pneumoniae in bile samples: A case series review.
AB  - Although Streptococcus pneumoniae is an important pathogen of humans,
      pneumococcal cholangitis is rare because of the rapid autolysis of S. pneumoniae.
      The aim of this case series was to review patients with bile cultures positive
      for S. pneumoniae. This study was a single center retrospective case series
      review of patients with S. pneumoniae in their bile at a tertiary-care cancer
      center between September 2002 and August 2015. Subjects consisted of all patients
      in whom S. pneumoniae was isolated in their bile during the study period. Bile
      specimens for culture were obtained from biliary drainage procedures such as
      endoscopic retrograde biliary drainage, endoscopic nasobiliary drainage, and
      percutaneous transhepatic biliary drainage. There were 20 patients with bile
      cultures positive for S. pneumoniae during the study period. All patients
      presented with extrahepatic obstructive jaundice due to hepatopancreatobiliary
      tumors. Nineteen of 20 patients underwent the placement of plastic intrabiliary
      tubes. The mean time between the first-time drainage and the positive culture was
      26 days (range 0-313 days). Although 12 of 20 patients met our definition of
      cholangitis, 5 were clinically treated with antibiotics based on a physician's
      assessment of whether there was a true infection. The present study is the
      largest case series of patients with S. pneumoniae in their bile. Based on our
      findings, the isolation of S. pneumoniae from bile may be attributed to the
      placement of biliary drainage devices. 

PMID- 27025901
TI  - Impaired ROS Scavenging System in Human Induced Pluripotent Stem Cells Generated
      from Patients with MERRF Syndrome.
AB  - Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a mitochondrial
      disorder characterized by myoclonus epilepsy, generalized seizures, ataxia and
      myopathy. MERRF syndrome is primarily due to an A to G mutation at mtDNA 8344
      that disrupts the mitochondrial gene for tRNA(Lys). However, the detailed
      mechanism by which this tRNA(Lys) mutation causes mitochondrial dysfunction in
      cardiomyocytes or neurons remains unclear. In this study, we generated human
      induced pluripotent stem cells (hiPSCs) that carry the A8344G genetic mutation
      from patients with MERRF syndrome. Compared with mutation-free isogenic hiPSCs,
      MERRF-specific hiPSCs (MERRF-hiPSCs) exhibited reduced oxygen consumption,
      elevated reactive oxygen species (ROS) production, reduced growth, and fragmented
      mitochondrial morphology. We sought to investigate the induction ability and
      mitochondrial function of cardiomyocyte-like cells differentiated from MERRF
      hiPSCs. Our data demonstrate that that cardiomyocyte-like cells (MERRF-CMs) or
      neural progenitor cells (MERRF-NPCs) differentiated from MERRF-iPSCs also
      exhibited increased ROS levels and altered antioxidant gene expression.
      Furthermore, MERRF-CMs or -NPCs contained fragmented mitochondria, as evidenced
      by MitoTracker Red staining and transmission electron microscopy. Taken together,
      these findings showed that MERRF-hiPSCs and MERRF-CM or -NPC harboring the A8344G
      genetic mutation displayed contained mitochondria with an abnormal
      ultrastructure, produced increased ROS levels, and expressed upregulated
      antioxidant genes. 

PMID- 27025903
TI  - Randomized Phase III study of gemcitabine plus S-1 versus gemcitabine plus
      cisplatin in advanced biliary tract cancer: Japan Clinical Oncology Group Study
      (JCOG1113, FUGA-BT).
AB  - A Phase II selection design trial was conducted to identify the most promising
      regimen for comparison with standard therapy in chemo-naive patients with
      unresectable or recurrent biliary tract cancer (JCOG0805). Gemcitabine plus S-1
      therapy showed better efficacy than S-1 monotherapy with acceptable safety in
      JCOG0805 study. Based on this result, a randomized Phase III trial was started in
      May 2013 to confirm the non-inferiority of gemcitabine plus S-1 therapy relative
      to gemcitabine plus cisplatin therapy, which is the current standard treatment
      for chemo-naive patients with unresectable or recurrent biliary tract cancer. A
      total of 350 patients will be accrued from 32 Japanese institutions within 4
      years. The primary endpoint is overall survival, while the secondary endpoints
      are progression-free survival, adverse events, serious adverse events, clinically
      significant adverse events, response rate and %planned dose. This trial has been
      registered with the UMIN Clinical Trials Registry
      (http://www.umin.ac.jp/ctr/index.htm) and the registration number is
      UMIN000010667. 

PMID- 27025904
TI  - Statistical shape analysis of subcortical structures using spectral matching.
AB  - Studying morphological changes of subcortical structures often predicate
      neurodevelopmental and neurodegenerative diseases, such as Alzheimer's disease
      and schizophrenia. Hence, methods for quantifying morphological variations in the
      brain anatomy, including groupwise shape analyses, are becoming increasingly
      important for studying neurological disorders. In this paper, a novel groupwise
      shape analysis approach is proposed to detect regional morphological alterations
      in subcortical structures between two study groups, e.g., healthy and
      pathological subjects. The proposed scheme extracts smoothed triangulated surface
      meshes from segmented binary maps, and establishes reliable point-to-point
      correspondences among the population of surfaces using a spectral matching
      method. Mean curvature features are incorporated in the matching process, in
      order to increase the accuracy of the established surface correspondence. The
      mean shapes are created as the geometric mean of all surfaces in each group, and
      a distance map between these shapes is used to characterize the morphological
      changes between the two study groups. The resulting distance map is further
      analyzed to check for statistically significant differences between two
      populations. The performance of the proposed framework is evaluated on two
      separate subcortical structures (hippocampus and putamen). Furthermore, the
      proposed methodology is validated in a clinical application for detecting
      abnormal subcortical shape variations in Alzheimer's disease. Experimental
      results show that the proposed method is comparable to state-of-the-art
      algorithms, has less computational cost, and is more sensitive to small
      morphological variations in patients with neuropathologies.

PMID- 27025906
TI  - Cutaneous Adverse Reaction to Mogamulizumab May Indicate Favourable Prognosis in
      Adult T-cell Leukaemia-lymphoma.

PMID- 27025905
TI  - Long-Term Effects of Concussion on Electrophysiological Indices of Attention in
      Varsity College Athletes: An Event-Related Potential and Standardized Low
      Resolution Brain Electromagnetic Tomography Approach.
AB  - This study investigated the effects of a past concussion on electrophysiological
      indices of attention in college athletes. Forty-four varsity football athletes
      (22 with at least one past concussion) participated in three neuropsychological
      tests and a two-tone auditory oddball task while undergoing high-density event
      related potential (ERP) recording. Athletes previously diagnosed with a
      concussion experienced their most recent injury approximately 4 years before
      testing. Previously concussed and control athletes performed equivalently on
      three neuropsychological tests. Behavioral accuracy and reaction times on the
      oddball task were also equivalent across groups. However, athletes with a
      concussion history exhibited significantly larger N2 and P3b amplitudes and
      longer P3b latencies. Source localization using standardized low-resolution brain
      electromagnetic tomography indicated that athletes with a history of concussion
      generated larger electrical current density in the left inferior parietal gyrus
      compared to control athletes. These findings support the hypothesis that
      individuals with a past concussion recruit compensatory neural resources in order
      to meet executive functioning demands. High-density ERP measures combined with
      source localization provide an important method to detect long-term neural
      consequences of concussion in the absence of impaired neuropsychological
      performance.

PMID- 27025907
TI  - Transmission-Type 2-Bit Programmable Metasurface for Single-Sensor and Single
      Frequency Microwave Imaging.
AB  - The programmable and digital metamaterials or metasurfaces presented recently
      have huge potentials in designing real-time-controlled electromagnetic devices.
      Here, we propose the first transmission-type 2-bit programmable coding
      metasurface for single-sensor and single- frequency imaging in the microwave
      frequency. Compared with the existing single-sensor imagers composed of active
      spatial modulators with their units controlled independently, we introduce
      randomly programmable metasurface to transform the masks of modulators, in which
      their rows and columns are controlled simultaneously so that the complexity and
      cost of the imaging system can be reduced drastically. Different from the single
      sensor approach using the frequency agility, the proposed imaging system makes
      use of variable modulators under single frequency, which can avoid the object
      dispersion. In order to realize the transmission-type 2-bit programmable
      metasurface, we propose a two-layer binary coding unit, which is convenient for
      changing the voltages in rows and columns to switch the diodes in the top and
      bottom layers, respectively. In our imaging measurements, we generate the random
      codes by computer to achieve different transmission patterns, which can support
      enough multiple modes to solve the inverse-scattering problem in the single
      sensor imaging. Simple experimental results are presented in the microwave
      frequency, validating our new single-sensor and single-frequency imaging system. 

PMID- 27025908
TI  - Unique Risks and Clinical Outcomes Associated With Extended-Spectrum beta
      Lactamase Enterobacteriaceae in Veterans With Spinal Cord Injury or Disorder: A
      Case-Case-Control Study.
AB  - OBJECTIVES To describe the burden of extended-spectrum beta-lactamase (ESBL)
      Enterobacteriaceae in veterans with spinal cord injury or disorder (SCI/D), to
      identify risk factors for ESBL acquisition, and to assess impact on clinical
      outcomes DESIGN Retrospective case-case-control study PATIENTS AND SETTING
      Veterans with SCI/D and utilization at a Veterans' Affairs medical center from
      January 1, 2012, to December 31, 2013. METHODS Patients with a positive culture
      for ESBL Klebsiella pneumoniae, Escherichia coli, or Proteus mirabilis were
      matched with patients with non-ESBL organisms by organism, facility, and level of
      care and to uninfected controls by facility and level of care. Inpatients were
      also matched by time at risk. Univariate and multivariate matched models were
      assessed for differences in risk factors and outcomes. RESULTS A total of 492
      cases (62.6% outpatients) were matched 1:1 with each comparison group. Recent
      prior use of fluoroquinolones and prior use of third- and fourth-generation
      cephalosporins were independently associated with ESBL compared to the non-ESBL
      group (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.77-3.84;
      P<.001 for fluoroquinolones and aOR, 3.86; 95% CI, 2.06-7.25; P<.001 for third-
      and fourth-generation cephalosporins) and the control group (aOR, 2.10; 95% CI,
      1.29-3.43; P = .003 for fluoroquinolones; and aOR, 3.31; 95% CI, 1.56-7.06;
      P=.002 for third- and fourth-generation cephalosporins). Although there were no
      differences in mortality rate, the ESBL group had a longer post-culture length of
      stay (LOS) than the non-ESBL group (incidence rate ratio, 1.36; 95% CI, 1.13
      1.63; P=.001). CONCLUSIONS All SCI/D patients with ESBL were more likely to have
      had recent exposure to fluoroquinolones or third- and fourth-generation
      cephalosporins, and hospitalized patients were more likely to have increased post
      culture LOS. Programs targeted toward reduced antibiotic use in SCI/D patients
      may prevent subsequent ESBL acquisition. Infect Control Hosp Epidemiol
      2016;37:768-776.

PMID- 27025910
TI  - Continuous Positive Airway Pressure to Prevent Neonatal Lung Injury: How Did We
      Get Here, and How Do We Improve?

PMID- 27025909
TI  - The Biology of Stature.

PMID- 27025911
TI  - Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer:
      evidence from 3,430 patients.
AB  - This study was designed to explore the association between elevated platelet to
      lymphocyte ratio (PLR) and prognosis of patients with non-small cell lung cancer
      (NSCLC) by meta-analysis. A total of 11 studies with 3,430 subjects were included
      and the combined hazard ratio (HR) and 95% confidence intervals (95% CI) were
      calculated. The data showed that elevated PLR predicted poor overall survival
      (OS) (HR = 1.42; 95% CI: 1.25-1.61, p < 0.001; I(2) = 63.6, Ph = 0.002) and poor
      disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.19; 95%CI:
      1.02-1.4, p = 0.027; I(2) = 46.8, Ph = 0.111). Subgroup analysis showed elevated
      PLR did not predict poor OS in patients included in large sample studies (HR =
      1.44; 95% CI: 0.94-2.21, p = 0.098) whereas patients with Caucasian ethnicity (HR
      = 1.59; 95%CI: 1.27-1.98, p < 0.001) and PLR cut-off value > 180 (HR = 1.61;
      95%CI: 1.3-1.99, p < 0.001) had enhanced prognostic efficiency for OS. Subgroup
      analysis also demonstrated that high PLR did not predict poor DFS/PFS in Asian
      patients. In conclusion, our meta-analysis suggested that elevated PLR was
      associated with poor OS and DFS/PFS in NSCLC. In addition, high PLR especially
      predicted poor OS in Caucasians but had no association with poor DFS/PFS in
      Asians.

PMID- 27025912
TI  - In the Loop: The Organization of Team-Based Communication in a Patient-Centered
      Clinical Collaboration System.
AB  - BACKGROUND: We describe the development and evaluation of a secure Web-based
      system for the purpose of collaborative care called Loop. Loop assembles the team
      of care with the patient as an integral member of the team in a secure space.
      OBJECTIVE: The objectives of this paper are to present the iterative design of
      the separate views for health care providers (HCPs) within each patient's secure
      space and examine patients', caregivers', and HCPs' perspectives on this separate
      view for HCP-only communication. METHODS: The overall research program includes
      cycles of ethnography, prototyping, usability testing, and pilot testing. This
      paper describes the usability testing phase that directly informed development. A
      descriptive qualitative approach was used to analyze participant perspectives
      that emerged during usability testing. RESULTS: During usability testing, we
      sampled 89 participants from three user groups: 23 patients, 19 caregivers, and
      47 HCPs. Almost all perspectives from the three user groups supported the need
      for an HCP-only communication view. In an earlier prototype, the visual
      presentation caused confusion among HCPs when reading and composing messages
      about whether a message was visible to the patient. Usability testing guided us
      to design a more deliberate distinction between posting in the Patient and Team
      view and the Health Care Provider Only view at the time of composing a message,
      which once posted is distinguished by an icon. CONCLUSIONS: The team made a
      decision to incorporate an HCP-only communication view based on findings during
      earlier phases of work. During usability testing we tested the separate
      communication views, and all groups supported this partition. We spent
      considerable effort designing the partition; however, preliminary findings from
      the next phase of evaluation, pilot testing, show that the Patient and Team
      communication is predominantly being used. This demonstrates the importance of a
      subsequent phase of the clinical trial of Loop to validate the concept and
      design.

PMID- 27025913
TI  - Percutaneous ultrasound-guided insertion of ventriculo-atrial shunts.
AB  - Ventriculo-atrial (VA) shunts have been in use for >60 years but less frequently
      so of late. This is due to a combination of the risk of cardiac complications,
      lack of expertise and a lengthy operation. We present our consecutive prospective
      series of 10 VA shunts inserted using a percutaneous method employing the
      Sonowand InviteTM neuronavigation system for both the distal and proximal
      catheters, over a 13-month period. We had two complications of cases needing
      revision, but our series highlights a safe and reproducible method of inserting a
      VA shunt. About 30% of the procedures were carried out by a trainee as the
      primary surgeon. This technique does not necessarily require the expertise of a
      complex hydrocephalus surgeon and is thus able to be in the armoury of any
      neurosurgeon needing to do a VA shunt procedure. The indications, operative data
      and outcomes of our patients are discussed. 

PMID- 27025914
TI  - Reconstructing the evolutionary history of gypsy retrotransposons in the Perigord
      black truffle (Tuber melanosporum Vittad.).
AB  - Truffles are ascomycete fungi belonging to genus Tuber, and they form
      ectomycorrhizal associations with trees and shrubs. Transposable elements
      constitute more than 50 % of the black Perigord truffle (Tuber melanosporum)
      genome, which are mainly class 1 gypsy retrotransposons, but their impact on its
      genome is unknown. The aims of this study are to investigate the diversity of
      gypsy retrotransposons in this species and their evolutionary history by
      analysing the reference genome and six resequenced genomes of different
      geographic accessions. Using the reverse transcriptase sequences, six different
      gypsy retrotransposon clades were identified. Tmt1 and Tmt6 are the most abundant
      transposable elements, representing 14 and 13 % of the T. melanosporum genome,
      respectively. Tmt6 showed a major burst of proliferation between 1 and 4 million
      years ago, but evidence of more recent transposition was observed. Except for
      Tmt2, the other clades tend to aggregate, and their mode of transposition
      excluded the master copy model. This suggests that each new copy has the same
      probability of transposing as other copies. This study provides a better view of
      the diversity and dynamic nature of gypsy retrotransposons in T. melanosporum.
      Even if the major gypsy retrotransposon bursts are old, some elements seem to
      have transposed recently, suggesting that they may continue to model the truffle
      genomes. 

PMID- 27025922
TI  - Plant epigenetics: from genotype to phenotype and back again.
AB  - A report on the Plant Epigenetics: From Genotype to Phenotype Keystone Symposium
      held in Taos, New Mexico, USA, 15-19 February, 2016.

PMID- 27025921
TI  - Flavanoids as Potential NEDD-4 Inhibitors: In Silico Discovery Using Molecular
      Docking and ADME Studies.
AB  - NEDD-4 are closely related E3 ubiquitin-protein ligases that include a C2 domain,
      three or four WW domains and a catalytic HECT ubiquitin ligase domain. The WW
      domains of NEDD-4 proteins recognize substrates for ubiquitination by binding the
      sequence L/PPxY (the PY-motif) present in target proteins. NEDD-4 functions as a
      suppressor of the epithelial Na+ channel (ENaC), which interacts with NEDD-4 WW
      domains via PY-motifs located at its C-terminus. Fifty compounds, all of them
      flavanoids, were subjected to molecular docking studies. The chemical structures
      were built, and docking studies were done using Schrodinger. ADMET studies were
      also performed. Furthermore, evidence is presented suggesting that interaction
      between NEDD-4 and the selected compounds from the database may also serve to
      regulate NEDD-4 stability, as this interaction leads to decreased NEDD-4 self
      ubiquitination. Collectively, the studies presented here further our
      understanding of the substrate specificity and regulation of NEDD-4. We have
      performed molecular docking and molecular dynamics simulation to study the
      interactions. The results of molecular dynamics simulation confirmed the binding
      mode of compounds.

PMID- 27025915
TI  - Depression and body mass index, differences by education: Evidence from a
      population-based study of adult women in the U.S. Buffalo-Niagara region.
AB  - The relationship between obesity and depression is well described. However, the
      evidence linking depression and body mass index (BMI) across the broad range of
      body size is less consistent. We examined the association between depressive
      symptoms and BMI in a sample of adult women in the Buffalo-Niagara region between
      1997 and 2001. Using logistic regression, we investigated whether increased
      weight status beyond normal-weight was associated with a higher prevalence of
      depressive symptoms, and if educational attainment modified the association
      between obesity and depression. There was a trend for increased weight status to
      be associated with higher depressive symptoms (obese II/III, OR 1.57, 95% CI 1.03
      2.41), whereas higher education was associated with lower odds of depressive
      symptoms, in an adjusted model including BMI (more than 12 but less than 16
      years, OR 0.70, 95% CI 0.49-0.98; 16 or more years of education, OR 0.61, 95% CI
      0.40-0.93). The association of being obese I with depressive symptoms was
      different for more educated (OR 2.15, 95% CI 1.27-3.62) compared to less educated
      women (OR 0.90, 95% CI 0.50-1.62); the sample was larger for the more educated
      women and reached statistical significance. There were no differences in the
      association for obese II/III women in strata of education. There was evidence of
      risk-difference heterogeneity (0.88, 95% CI 0.84-0.93). In this population-based
      sample of women in western New York state, increased weight was negligibly
      associated with depressive symptoms. The association of being obese I with
      depressive symptoms was different for more compared to less educated women.

PMID- 27025923
TI  - Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical
      trial cohort.
AB  - Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations
      in cancer patients. A population-based retrospective cohort was identified from
      31 Phase 2-3 oncology trials (excluding targeted therapies) conducted from 1985
      to 2005 to evaluate background rates of LC elevations in patients (n = 3998) with
      or without liver metastases. Patients with baseline liver metastases (29% of
      patients) presented with a 3% prevalence of alanine transaminase (ALT) >= 3x
      upper limits normal (ULN) and 0.2% prevalence of bilirubin >= 3xULN. During
      follow-up, the incidence (per 1000 person-months) of new onset ALT elevations
      >=3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2 (95% CI: 0.9, 4.5) in patients without
      and with liver metastases, respectively. No new incident cases of ALT and
      bilirubin elevations suggestive of severe liver injury occurred among those with
      liver metastases; a single case occurred among those without metastasis.
      Regardless of the presence of liver metastases, LC elevations were rare in cancer
      patients during oncology trials, which may be due to enrollment criteria. Our
      study validates uniform thresholds for detection of LC elevations in oncology
      studies and serves as an empirical referent point for comparing liver enzyme
      abnormalities in oncology trials of novel targeted therapies. These data support
      uniform LC stopping criteria in oncology trials. 

PMID- 27025924
TI  - Efficacy of Mycoplasma hyopneumoniae vaccination before and at weaning against
      experimental challenge infection in pigs.
AB  - BACKGROUND: Commercial bacterins are widely used at weaning to control Mycoplasma
      hyopneumoniae infections in pigs. However, it is not known whether the efficacy
      of vaccinating against M. hyopneumoniae can be influenced by the weaning process
      when vaccination is applied at the day of weaning. The present study assessed the
      efficacy of a single M. hyopneumoniae vaccination (Ingelvac MycoFLEX(r)) three
      days before weaning (V1) or at weaning (V2) against experimental challenge
      infection. Four weeks after vaccination, groups V1 and V2 (n = 20 pigs each) and
      a non-vaccinated, positive control group (PCG) (n = 20) were endotracheally
      inoculated with a virulent M. hyopneumoniae field strain. Five pigs were used as
      a negative control group. All pigs were euthanized 5 weeks after challenge. The
      main parameters investigated included macroscopic and histopathological lung
      lesions at necropsy, immunofluorescence (IF) staining and quantitative real-time
      PCR (qPCR) on broncho-alveolar lavage (BAL) fluid for quantifying M.
      hyopneumoniae. RESULTS: The average macroscopic lung lesion scores in groups V1,
      V2 and PCG were 0.54, 0.88 and 1.04, respectively (P > 0.05). The average
      lymphohistiocytic infiltration scores in groups V1, V2 and PCG were 2.95, 3.16
      and 3.61, respectively (P < 0.05). The average IF scores were: V1 = 1.13, V2 =
      1.19 and PCG = 1.25 (P > 0.05), the qPCR values were: V1 = 10(2.94), V2 =
      10(2.76) and PCG = 10(3.23) (P > 0.05). All pigs of the negative control group
      remained negative throughout the study. CONCLUSIONS: Both vaccinated groups had
      lower numbers of macroscopic and histopathological lung lesions, and lower
      numbers of M. hyopneumoniae organisms in the BAL fluid compared to the PCG.
      However, no firm conclusions could be made on whether weaning negatively
      influences the efficacy of M. hyopneumoniae vaccination, since significant
      differences between the treatment groups were only obtained for the
      histopathological lung lesions. This could be attributed to the fact that milder
      macroscopic lung lesions were produced in the inoculated pigs, when compared to
      previous trials conducted by the same group. Further research under field
      conditions is warranted to assess possible differences between the two
      vaccination strategies.

PMID- 27025925
TI  - The molecular pathway of psoralidin-induced apoptosis in HepG2 cell line.
AB  - OBJECTIVE: To test the role of psoralidin in human liver cancer HepG2 cells in
      vitro. METHODS: Cell viability was assessed by methylthiazolyldiphenyl-tetrazolum
      bromide assay and apoptotic cells were labeled by annexin V then sorted by flflow
      cytometry. Protein expressions of caspase-3, caspase-8, caspase-9, Bax, Bid, Bcl
      2, Bcl-xL and p53 were examined by western blot while activity of caspase-3, -8
      and -9 were also determined. RESULTS: Psoralidin reduces cell viability greatly
      in a time dependent manner (64%, 40%, 21%, 12% at 2, 6, 24 and 48 h treatment
      with 64 MUmol/L psoralidin respectively) and up-regulates activities of caspase
      3, -8 and -9 in a concentration dependent manner (between 4 to 64 MUmol/L).
      Psoralidin also increases the expression of pro-apoptosis genes Bax, Bid and p53
      while decreases the expression of pro-survival genes Bcl-2 and Bcl-xL, both in a
      concentration dependent manner between 4 and 64 MUmol/L (P<0.05 at 16 and 64
      MUmol/L). Caspase-3 inhibitor (Ac-DEVD-CHO at concentrations between 10 to 20
      MUmol/L), p53 inhibitor (pififithrin-alpha at 5 MUmol/L) and cyclosporin A can
      attenuate the apoptotic effect of psoralidin. CONCLUSION: The cytotoxic role of
      psoralidin might work through both intrinsic and extrinsic apoptotic pathway.

PMID- 27025926
TI  - Associations between preoperative OCT parameters and visual outcome 3 months
      postoperatively in patients undergoing vitrectomy for idiopathic epiretinal
      membrane.
AB  - PURPOSE: To evaluate the effect of preoperative optical coherence tomography
      (OCT) features on postoperative visual acuity and change in acuity after
      epiretinal membrane (ERM) surgery. METHODS: This was a retrospective consecutive
      case series of patients with symptomatic idiopathic ERMs who underwent vitrectomy
      and membrane peel between 2008 and 2013. The main outcomes were postoperative
      letter score and change in letter score. The association between visual acuity
      and OCT features was estimated using linear regression, correcting for important
      baseline covariates. OCT features included central foveal thickness, maximum
      retinal thickness, retinal cross-sectional area, central photoreceptor thickness,
      central epiretinal membrane, intraretinal cyst presence and location, retinal
      contraction, foveal ellipsoid zone and external limiting membrane integrity, and
      pseudoholes. RESULTS: A total of 79 patients were included in the study. Mean
      visual acuity was 65.0 letters preoperatively and 68.9 letters postoperatively,
      with average follow-up of 92 days. Better postoperative visual acuity was
      associated with the presence of preoperative retinal contraction (6.4 letters P =
      0.027) and lower preoperative maximum retinal thickness values (0.34 letters per
      10 MUm reduction, P = 0.003). Change in visual acuity was associated with
      preoperative foveal ellipsoid zone attenuation (6.6 letters more improvement when
      present, P = 0.013). Preoperative pseudoholes were associated with a smaller
      change in visual acuity (7.4 letters less improvement, P = 0.034). No other OCT
      features were significant, including intraretinal cyst presence and location.
      Better preoperative visual acuity was associated with better postoperative
      acuity, but less change in visual acuity postoperatively. CONCLUSION:
      Preoperative maximum retinal thickness and retinal contraction were predictive of
      better postoperative visual acuity, while patients with a preoperative attenuated
      foveal ellipsoid zone were most likely to improve. Patients with preoperative
      pseudoholes had slightly worse visual acuity postoperatively. Although better
      preoperative vision was associated with better postoperative vision, it was
      associated with less change in visual acuity, emphasizing the importance of
      careful consideration of the desired surgical goals before advising surgery for
      ERM.

PMID- 27025927
TI  - Changes in Gab2 phosphorylation and interaction partners in response to
      interleukin (IL)-2 stimulation in T-lymphocytes.
AB  - Interleukin-2 (IL-2) stimulation results in T-cell growth as a consequence of
      activation of highly sophisticated and fine-tuned signaling pathways. Despite
      lacking intrinsic enzymatic activity, scaffold proteins such as Gab2, play a
      pivotal role in IL-2-triggered signal transduction integrating, diversifying and
      amplifying the signal by serving as a platform for the assembly of effectors
      proteins. Traditionally, Gab2-mediated protein recruitment was believed to solely
      depend on cytokine-induced phosphotyrosine moieties. At present, phosphorylation
      on serine/threonine residues is also emerging as a key mediator of Gab2-dependent
      signal regulation. Despite its relevance, IL-2-triggered regulation on Gab2
      phosphorylation is yet poorly understood. Combining antibody- and TiO2-based
      enrichment of the scaffold protein with SILAC quantitative mass spectrometry we
      disclose the prominent regulation IL-2 exerts on Gab2 serine/threonine
      phosphorylation by showing that at least 18 serines and 1 threonine, including
      previously non-reported ones, become phosphorylated in response to cytokine
      stimulation. Additionally, we decipher the interactome of the docking protein in
      resting and cytokine-treated T-lymphocytes and besides well-known Gab2
      interactors we discover three novel cytokine-inducible Gab2-binding proteins.
      Thus, our data provide novel insights and a wealth of candidates for future
      studies that will shed light into the role of Gab2 in IL-2-initiated signal
      transduction. 

PMID- 27025929
TI  - Serum VEGF, EGF, basic FGF, and acidic FGF levels and their association with
      disease activity and extra-articular symptoms in ankylosing spondylitis.

PMID- 27025928
TI  - Endometriosis and Risk of Coronary Heart Disease.
AB  - BACKGROUND: Endometriosis is a prevalent gynecologic disease associated with
      systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid
      profile that may increase women's risk for coronary heart disease (CHD). METHODS
      AND RESULTS: We examined the prospective association between laparoscopically
      confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses'
      Health Study II (1989-2009). Participants with a history of heart disease and
      stroke were excluded. When compared with women without endometriosis, women with
      laparoscopically confirmed endometriosis had a higher risk of myocardial
      infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98),
      angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft
      surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these
      CHD end points combined (1.62; 1.39-1.89), independent of potential demographic,
      anthropometric, family history, reproductive, and lifestyle confounders. Relative
      risk for the combined CHD end point was highest among women aged <=40 years
      (3.08; 2.02-4.70) and decreased as age increased (40< age <=50 years, 1.65; 1.35
      2.02; 50< age <=55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P
      value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was
      associated with higher risk of combined CHD compared with not having had a
      hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the
      association between endometriosis and CHD could be explained by greater frequency
      of hysterectomy/oophorectomy and earlier age at surgery after endometriosis
      diagnosis. CONCLUSIONS: In this large, prospective cohort, laparoscopically
      confirmed endometriosis was associated with increased risk of CHD. The
      association was strongest among young women. Hysterectomy/oophorectomy was
      associated with higher risk of CHD and could partially explain the association
      between endometriosis and CHD.

PMID- 27025930
TI  - Growth and antioxidant production of Spirulina in different NaCl concentrations.
AB  - OBJECTIVE: To evaluate the quantity of Spirulina cultured in seawater, salt
      tolerant strains were screened out and their growth and antioxidant accumulation
      were studied in different salt concentrations RESULTS: Salt tolerance of five
      Spirulina strains were investigated with modified Zarrouk medium (with 200-800 mM
      NaCl). All strains grew well with 400 mM NaCl; their growth rates were almost
      same as in the control medium. Spirulina strains FACHB-843 (SP843) and FACHB-972
      (SP972) had the highest salt tolerance their growth rates in 600 mM NaCl were
      nearly same as the control. Both strains produced more carotene, phycocyanin,
      polysaccharides, proline and betaine in 400-600 mM NaCl than the control. Salt
      stress also induced them to produce higher activities of superoxide dismutase and
      peroxidase. Total antioxidant capacities of SP843 and SP972 peaked at 600 and 400
      mM NaCl, respectively. CONCLUSION: Spirulina strains cultured with seawater
      accumulate more bioactive substances and will have a higher nutritive value.

PMID- 27025931
TI  - Efficient kinetic resolution of secondary alcohols using an organic solvent
      tolerant esterase in non-aqueous medium.
AB  - OBJECTIVE: To identify an esterase-mediated kinetic resolution of secondary
      alcohols in non-aqueous medium. RESULTS: An esterase, EST4, from a marine mud
      metagenomic library, showed high activity and enantioselectivity for the kinetic
      resolution of secondary alcohols in non-aqueous medium. Using 1-phenylethanol as
      the model alcohol, the effects of organic solvents, acyl donors, molar ratio,
      temperatures and biocatalyst loading on the kinetic resolution catalyzed by the
      EST4 whole-cell biocatalyst were investigated and optimized. The optimized
      methodology was effective on resolving 16 various racemic secondary alcohols in
      neat n-hexane, providing excellent enantiomeric excess (up to 99.9 % ee).
      Moreover, EST4 exhibited a strong tolerance for high substrate concentration (up
      to 1 M), and the optical purity of the desired secondary alcohols was kept above
      99 % ee. CONCLUSION: The esterase EST4 is a promising biocatalyst for the
      enantioselective synthesis of various alcohols and esters with interesting
      practical applications.

PMID- 27025932
TI  - The First Space-Related Study of a Kombucha Multimicrobial Cellulose-Forming
      Community: Preparatory Laboratory Experiments.
AB  - Biofilm-forming microbial communities are known as the most robust assemblages
      that can survive in harsh environments. Biofilm-associated microorganisms display
      greatly increased resistance to physical and chemical adverse conditions, and
      they are expected to be the first form of life on Earth or anywhere else.
      Biological molecules synthesized by biofilm -protected microbiomes may serve as
      markers of the nucleoprotein life. We offer a new experimental model, a kombucha
      multimicrobial culture (KMC), to assess a structural integrity of a widespread
      microbial polymer - cellulose - as a biosignature of bacteria-producers for the
      multipurpose international project "BIOlogical and Mars Experiment (BIOMEX)",
      which aims to study the vitality of pro- and eukaryotic organisms and the
      stability of organic biomolecules in contact with minerals to analyze the
      detectability of life markers in the context of a planetary background. In this
      study, we aimed to substantiate the detectability of mineralized cellulose with
      spectroscopy and to study the KMC macrocolony phenotype stability under adverse
      conditions (UV, excess of inorganics etc.). Cellulose matrix of the KMC
      macrocolony has been mineralized in the mineral-water interface under assistance
      of KMC-members. Effect of bioleached ions on the cellulose matrix has been
      visible, and the FT-IR spectrum proved changes in cellulose structure. However,
      the specific cellulose band vibration, confirming the presence of beta(1,4)
      linkages between monomers, has not been quenched by secondary minerals formed on
      the surface of pellicle. The cellulose-based KMC macrocolony phenotype was in a
      dependence on extracellular matrix components (ionome, viriome, extracellular
      membrane vesicles), which provided its integrity and rigidness in a certain
      extent under impact of stressful factors.

PMID- 27025933
TI  - Chemical cues from females trigger male courtship behaviour in grasshoppers.
AB  - Gomphocerine grasshoppers use species-specific calling songs for sex recognition
      and mate attraction. In two closely related species, Chorthippus biguttulus and
      C. mollis, acoustic communication is the only experimentally characterized
      communication channel that elicits male courtship behaviour. However, courtship
      in these species involves extensive close-range interactions that are likely to
      be mediated by other signalling modalities, in particular chemical cues. We
      developed a bioassay to determine if female cuticular hydrocarbons (CHCs) act as
      chemical cues that induce courtship behaviour, and if males assess variation in
      CHCs to determine whether or not to court a female. The results of this approach
      provide evidence that grasshopper males use species- and sex-specific information
      from CHC signals and respond with a courtship song to the CHC profile of
      conspecific females but not to the CHC profile of heterospecific females and
      conspecific males. We conclude that males of C. biguttulus and C. mollis use
      multimodal channels for mating decisions, based on both acoustic and olfactory
      cues. We discuss various factors that might favour the evolution of male
      choosiness in grasshoppers.

PMID- 27025934
TI  - Change of ultraviolet light transmittance in growing chicken and quail eyes.
AB  - The ocular media transmittance (OMT), the amount of light transmitted by the
      ocular media (the cornea, aqueous humour, lens and vitreous humour) to the
      retina, determines the sensitivity of vertebrate eyes to short-wavelength light,
      such as ultraviolet (UV). Earlier, we have measured the OMT of adult birds from a
      range of species and found that smaller eyes transmitted more UV-light to the
      retina than larger eyes. In the current study we measured OMT during post-hatch
      development in Japanese quails and domestic chickens. We show that in both
      species, OMT decreases as the eye size increases similarly to that what was found
      across various species, but that quails have lower OMT than expected from eye
      size. In both species, lens transmittance decreases linearly with lens thickness
      suggesting that UV-transmittance through the lenses is not actively controlled,
      but instead determined by UV-absorbance and scattering that occur in all
      biological tissues. Contrary to earlier assumptions of high cornea transmittance,
      we found that cornea transmittance is more variable, substantially influencing
      whole eye transmittance in all age groups of quail and in young chickens. It
      seems that additional absorbing pigments are used to more actively control cornea
      transmittance and thereby also overall OMT.

PMID- 27025935
TI  - Fuzzy Logic Modelling of the Effects of Pollution on Domestic Roof-Harvested
      Rainwater Quality in Residential and Industrial Environments.
AB  - This study presents the effects of environmental pollution on the quality of
      domestic roof-harvested rainwater (DRHRW) using fuzzy comprehensive assessment
      (FCA). Seven metals (Cu, Cd, Pb, Zn, Fe, Ca, and Mg) and six water-quality
      parameters (Acidity, PO4 (3-), SO4 (2-), NO3 (-) , Cl(-), and pH) were
      investigated in DRHRW sampled from 12 sampling points each from Ibadan
      (residential) and Lagos (industrial) environments, Nigeria. The results of these
      parameters were formulated into membership function fuzzy matrices based on four
      contamination classifications of high, marginal, low, and poor qualities using
      regulatory limits as criteria. The products membership function matrices and
      weight matrices generated indices that classified the degree of anthropogenic
      activity impact on the sites. Results of FCA classified the DRHRW from
      residential environment as between high and marginal quality, whereas DRHRW from
      industrial environment is classified between marginal and low quality. Lead and
      Cd were major contaminants of concern found in these harvested water. 

PMID- 27025936
TI  - Comparison of traditional surgery and laser treatment of incontinent great
      saphenous vein. Results of a meta-Analysis.
AB  - AIM: This paper aims to compare EVLA to traditional surgery, by evaluating the
      incidence of recurrences. MATERIAL OF STUDY: We performed a meta-analysis to
      challenge both surgical and LASER treatment, using, as clinical outcome, the
      presence or the absence of reflux. A systematic review of literature about the
      treatment of varicose veins was performed, searching in the following databases:
      PUBMED-MEDLINE, Cochrane Library. Search terms considered were: stripping, HL/S,
      surgery, LASER, EVL*, varicose vein, GSV, saphenous vein. Only RCTs based at
      least on sixmonths follow-up were considered eligible in the study.
      Methodological quality of the included studies was evaluated using Cochrane
      Collaboration Bias Risk Assessment Tool. Effects of the dichotomous variables
      taken in consideration were evaluated using pooled risk-ratios with 95% C.I.
      Articles were evaluated initially from abstracts; eligible papers were fulltext
      examined. RESULTS: We have considered 2 groups, A and B. A Group: 756 legs
      treated with conventional surgical procedure; B Group: 755 legs treated with EVLA
      technique. A Group showed 175 post-procedure recurrences, while B showed 97
      recurrences. The average O.R. was 1.72; minimum O.R. was of .497 while the
      maximum was of 8.064. DISCUSSION: The obtained OR average value is 1.72 with a
      95% C.I. of 0.94-3.12, which includes the value 1, contrary to the criteria for
      rejection of the null hypothesis. For this reason there is not a statistically
      significant difference between the results obtained by the two techniques.
      CONCLUSIONS: The endovascular laser ablation (EVLA) does not prove to be superior
      in terms of recurrence, to the surgical technique. However, it remains a viable
      treatment option in patients with impaired great saphenous vein, reducing
      postoperative pain and hospital stay. KEY WORDS: Laser therapy, Meta-analysis,
      Saphenous vein, Surgery, Venous insufficiency.

PMID- 27025937
TI  - Impulsivity and Suicidality in Adolescent Inpatients.
AB  - Suicide is the second leading cause of death among adolescents, and impulsivity
      has emerged as a promising marker of risk. The present study tested whether
      distinct domains of impulsivity are differentially associated with suicide
      ideation, plans, and attempts. Adolescents (n = 381; boys = 106, girls = 275)
      aged 13-19 years (M = 15.62, SD = 1.41) were recruited from an acute, residential
      treatment program. Within 48 h of admission to the hospital, participants were
      administered structured clinical interviews assessing mental health disorders and
      suicidality. Following these interviews, participants completed self-report
      questionnaires assessing symptom severity and impulsivity. Consistent with past
      research, an exploratory factor analysis of our 90-item impulsivity instrument
      resulted in a three-factor solution: Pervasive Influence of Feelings, Feelings
      Trigger Action, and Lack of Follow-Through. Concurrent analysis of these factors
      confirmed hypotheses of unique associations with suicide ideation and attempts in
      the past month. Specifically, whereas Pervasive Influence of Feelings (i.e.,
      tendency for emotions to shape thoughts about the self and the future) is
      uniquely associated with greater suicidal ideation, Feelings Trigger Action
      (i.e., impulsive behavioral reactivity to emotions) is uniquely associated with
      the occurrence of suicide attempts, even after controlling for current
      psychiatric diagnoses and symptoms. Exploratory gender analyses revealed that
      these effects were significant in female but not male adolescents. These findings
      provide new insight about how specific domains of impulsivity differentially
      increase risk for suicide ideation and attempts. Implications for early
      identification and prevention of youth suicide are discussed.

PMID- 27025939
TI  - Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic
      resistance in ICU patients: a retrospective observational study.
AB  - PURPOSE: Antibiotic de-escalation is promoted to limit prolonged exposure to
      broad-spectrum antibiotics, but proof that it prevents the emergence of
      resistance is lacking. We evaluated determinants of antibiotic de-escalation in
      an attempt to assess whether the latter is associated with a lower emergence of
      antimicrobial resistance. METHODS: Antibiotic treatments, starting with empirical
      beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in
      a tertiary intensive care unit (ICU) and categorized as continuation, de
      escalation or escalation of the empirical antimicrobial treatment. Determinants
      of the de-escalation or escalation treatments were identified by multivariate
      logistic regression; the continuation category was used as the reference group.
      Using systematically collected diagnostic and surveillance cultures, we estimated
      the cumulative incidence of antimicrobial resistance following de-escalation or
      continuation of therapy, with adjustment for ICU discharge and death as competing
      risks. RESULTS: Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 %) were
      classified as escalation of the antimicrobial treatment and 121 (25 %) were
      classified as de-escalation, mainly through replacement of the originally
      prescribed antibiotics with those having a narrower spectrum. In multivariate
      analysis, de-escalation was associated with the identification of etiologic
      pathogens (p < 0.001). The duration of the antibiotic course in the ICU in de
      escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7)
      days, respectively (p < 0.001). Mortality did not differ between patients in the
      de-escalation and continuation categories. The cumulative incidence estimates of
      the emergence of resistance to the initial beta-lactam antibiotic on day 14 were
      30.6 and 23.5 % for de-escalation and continuation, respectively (p = 0.22). For
      the selection of multi-drug resistant pathogens, these values were 23.5 (de
      escalation) and 18.6 % (continuation) respectively (p = 0.35). CONCLUSION: The
      emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal
      beta-lactam antibiotics was not lower following de-escalation.

PMID- 27025938
TI  - Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in
      patients and their family caregivers.
AB  - Outcomes after acute respiratory distress syndrome (ARDS) are similar to those of
      other survivors of critical illness and largely affect the nerve, muscle, and
      central nervous system but also include a constellation of varied physical
      devastations ranging from contractures and frozen joints to tooth loss and
      cosmesis. Compromised quality of life is related to a spectrum of impairment of
      physical, social, emotional, and neurocognitive function and to a much lesser
      extent discrete pulmonary disability. Intensive care unit-acquired weakness
      (ICUAW) is ubiquitous and includes contributions from both critical illness
      polyneuropathy and myopathy, and recovery from these lesions may be incomplete at
      5 years after ICU discharge. Cognitive impairment in ARDS survivors ranges from
      70 to 100 % at hospital discharge, 46 to 80 % at 1 year, and 20 % at 5 years, and
      mood disorders including depression and post-traumatic stress disorder (PTSD) are
      also sustained and prevalent. Robust multidisciplinary and longitudinal
      interventions that improve these outcomes are still uncertain and data in our
      literature are conflicting. Studies are needed in family members of ARDS
      survivors to better understand long-term outcomes of the post-ICU family syndrome
      and to evaluate how it affects patient recovery. 

PMID- 27025940
TI  - Nurses' Perceptions and Practices Toward Clinical Alarms in a Transplant Cardiac
      Intensive Care Unit: Exploring Key Issues Leading to Alarm Fatigue.
AB  - BACKGROUND: Intensive care units (ICUs) are complex work environments where false
      alarms occur more frequently than on non-critical care units. The Joint
      Commission National Patient Safety Goal .06.01.01 targeted improving the safety
      of clinical alarm systems and required health care facilities to establish alarm
      systems safety as a hospital priority by July 2014. An important initial step
      toward this requirement is identifying ICU nurses' perceptions and common
      clinical practices toward clinical alarms, where little information is available.
      OBJECTIVE: Our aim was to determine perceptions and practices of
      transplant/cardiac ICU (TCICU) nurses toward clinical alarms and benchmark the
      results against the 2011 Healthcare Technology Foundation's (HTF) Clinical Alarms
      Committee Survey. METHODS: A quality improvement project was conducted on a 20
      bed TCICU with 39 full- and part-time nurses. Nurses were surveyed about their
      perceptions and attitudes toward and practices on clinical alarms using an
      adapted HTF clinical alarms survey. Results were compared to the 2011 HTF data.
      Correlations among variables were examined. RESULTS: All TCICU nurses provided
      usable responses (N=39, 100%). Almost all nurses (95%-98%) believed that false
      alarms are frequent, disrupt care, and reduce trust in alarm systems, causing
      nurses to inappropriately disable them. Unlike the 2011 HTF clinical alarms
      survey results, a significantly higher percentage of our TCICU nurses believed
      that existing devices are complex, questioned the ability and adequacy of the new
      monitoring systems to solve alarm management issues, pointed to the lack of
      prompt response to alarms, and indicated the lack of clinical policy on alarm
      management (P<.01). Major themes in the narrative data focused on nurses'
      frustration related to the excessive number of alarms and poor usability of the
      cardiac monitors. A lack of standardized approaches exists in changing patients'
      electrodes and individualizing parameters. Around 60% of nurses indicated they
      received insufficient training on bedside and central cardiac monitors. A
      correlation also showed the need for training on cardiac monitors, specifically
      for older nurses (P=.01). CONCLUSIONS: False and non-actionable alarms continue
      to desensitize TCICU nurses, perhaps resulting in missing fatal alarms. Nurses'
      attitudes and practices related to clinical alarms are key elements for designing
      contextually sensitive quality initiatives to fight alarm fatigue. Alarm
      management in ICUs is a multidimensional complex process involving usability of
      monitoring devices, and unit, clinicians, training, and policy-related factors.
      This indicates the need for a multi-method approach to decrease alarm fatigue and
      improve alarm systems safety.

PMID- 27025941
TI  - Genome scale patterns of supercoiling in a bacterial chromosome.
AB  - DNA in bacterial cells primarily exists in a negatively supercoiled state. The
      extent of supercoiling differs between regions of the chromosome, changes in
      response to external conditions and regulates gene expression. Here we report the
      use of trimethylpsoralen intercalation to map the extent of supercoiling across
      the Escherichia coli chromosome during exponential and stationary growth phases.
      We find that stationary phase E. coli cells display a gradient of negative
      supercoiling, with the terminus being more negatively supercoiled than the origin
      of replication, and that such a gradient is absent in exponentially growing
      cells. This stationary phase pattern is correlated with the binding of the
      nucleoid-associated protein HU, and we show that it is lost in an HU deletion
      strain. We suggest that HU establishes higher supercoiling near the terminus of
      the chromosome during stationary phase, whereas during exponential growth DNA
      gyrase and/or transcription equalizes supercoiling across the chromosome. 

PMID- 27025942
TI  - The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP):
      A Comprehensive Global Assessment.
AB  - Fibrodysplasia ossificans progressiva (FOP) leads to disabling heterotopic
      ossification (HO) from episodic flare-ups. However, the natural history of FOP
      flare-ups is poorly understood. A 78-question survey on FOP flare-ups, translated
      into 15 languages, was sent to 685 classically-affected patients in 45 countries
      (six continents). Five hundred patients or knowledgeable informants responded
      (73%; 44% males, 56% females; ages: 1 to 71 years; median: 23 years). The most
      common presenting symptoms of flare-ups were swelling (93%), pain (86%), or
      decreased mobility (79%). Seventy-one percent experienced a flare-up within the
      preceding 12 months (52% spontaneous; 48% trauma-related). Twenty-five percent of
      those who had received an intramuscular injection reported an immediate flare-up
      at the injection site, 84% of whom developed HO. Axial flare-ups most frequently
      involved the back (41.6%), neck (26.4%), or jaw (19.4%). Flare-ups occurred more
      frequently in the upper limbs before 8 years of age, but more frequently in the
      lower limbs thereafter. Appendicular flare-ups occurred more frequently at
      proximal than at distal sites without preferential sidedness. Seventy percent of
      patients reported functional loss from a flare-up. Thirty-two percent reported
      complete resolution of at least one flare-up and 12% without any functional loss
      (mostly in the head or back). The most disabling flare-ups occurred at the
      shoulders or hips. Surprisingly, 47% reported progression of FOP without obvious
      flare-ups. Worldwide, 198 treatments were reported; anti-inflammatory agents were
      most common. Seventy-five percent used short-term glucocorticoids as a treatment
      for flare-ups at appendicular sites. Fifty-five percent reported that
      glucocorticoids improved symptoms occasionally whereas 31% reported that they
      always did. Only 12% reported complete resolution of a flare-up with
      glucocorticoids. Forty-three percent reported rebound symptoms within 1 to 7 days
      after completing a course of glucocorticoids. This study is the first
      comprehensive global assessment of FOP flare-ups and establishes a critical
      foundation for the design and evaluation of future clinical trials.

PMID- 27025943
TI  - Valosin-containing protein-related amyotrophic lateral sclerosis in Japan.

PMID- 27025944
TI  - Valosin-containing protein-related amyotrophic lateral sclerosis in Japan.

PMID- 27025945
TI  - Miscarriage in Australia: The geographical inequity of healthcare services.
AB  - Complications in early pregnancy can lead to pregnancy loss (miscarriage) and
      ultimately the presentation of a woman to their local emergency department (ED).
      Miscarriage is a common occurrence, with one in six pregnancies resulting in
      pregnancy loss.(1) Unfortunately medical and nursing care does not change the
      likelihood of a threatened miscarriage progressing to pregnancy loss; this is a
      highly emotional and stressful time for the woman and her family. Research has
      shown that women have often felt dissatisfied with the care provided in the
      emergency department and have reported lower levels of satisfaction (Geller et
      al., 2010(2), Indig et al., 2011(3)). This paper explores the challenges in the
      provision of emergency department healthcare for women presenting to metropolitan
      EDs and compares these to those faced by women who present to non-metropolitan
      EDs with early pregnancy complications. 

PMID- 27025946
TI  - Adelbert Ames Jr., the ophthalmologist who changed the perspective by means of an
      optical illusion.

PMID- 27025947
TI  - Intensity-modulated radiation therapy use for the localized treatment of thyroid
      cancer: Nationwide practice patterns and outcomes.
AB  - In the absence of randomized data, the optimal approach to adjuvant radiation
      therapy in locally advanced thyroid cancer remains unclear. We employed a large
      retrospective analysis to assess the best available evidence of a potential
      beneficial impact of intensity-modulated versus 3D-conformal radiotherapy (IMRT
      vs. 3D-CT). Retrospective analysis of adult thyroid cancer diagnosed between 2004
      and 2011 within the National Cancer Database. Among patients treated with
      radiation therapy (N = 855), the use of IMRT (N = 437) increased among both
      comprehensive and academic centers (both p < 0.001), but not community hospitals
      (p = 0.43). Receipt of IMRT was associated with adverse clinical factors in
      multivariable analysis, including positive surgical margins, non-DTC histologies,
      and nodal metastases (all p < 0.001). IMRT use was associated with a
      significantly higher dose of radiation (60.7 vs. 52.4 Gy, p < 0.001). In
      multivariable analyses, receipt of IMRT demonstrated a trend toward improved
      overall survival (HR, 0.67; 95 % CI, 0.40-1.10; p = 0.115). This study presents
      the largest cohort to date examining receipt of IMRT in patients with locally
      advanced thyroid cancer and demonstrates an association between IMRT, treatment
      at a tertiary care center, higher total dose, and comparable or superior outcomes
      compared to patients treated with 3D conformal techniques despite more adverse
      disease features. In the absence of adequately powered prospective randomized
      trials, our retrospective analysis provides empirical evidence to support the use
      in these patients of dose escalation and IMRT, particularly at tertiary care
      centers. 

PMID- 27025948
TI  - SIADH: differential diagnosis and clinical management.
AB  - Despite the widespread prevalence of hyponatremia and its deleterious effects on
      patients, it is often overlooked and consequently undertreated. This set of four
      cases provides practical advice on how to identify, diagnose, and treat patients
      with syndrome of inappropriate antidiuretic hormone (SIADH). The first steps that
      a physician should take when diagnosing a patient with hyponatremia are to assess
      the severity of neurological symptoms, and check the patient's volemic status in
      order to determine whether emergency treatment with hypertonic saline is
      indicated. Laboratory tests are necessary for the diagnosis of SIADH, but, in
      severe, symptomatic cases of hyponatremia, patients need treatment before the
      results of laboratory tests can be obtained. In this series, Case 1 demonstrates
      how awareness of hyponatremia led to early diagnosis and treatment. Case 2
      demonstrates how multiple causes of hyponatremia can be diagnosed and managed
      sequentially. Case 3 illustrates how a patient with severe symptoms should be
      treated while waiting for laboratory test results to confirm diagnosis. Case 4
      examines how the priorities of a patient should inform the management of their
      chronic SIADH, using palliative care of a patient with small-cell lung cancer as
      an example. There are several factors that clinicians should consider when making
      treatment decisions, including signs and symptoms, risks and benefits of
      different treatments, psychosocial factors, and the patient's wishes. All the
      available treatment options have a place in the management of patients with
      SIADH, and a physician should individualize decisions based on a patient's needs
      and priorities.

PMID- 27025949
TI  - Depletion controlled surface deposition of uncharged colloidal spheres from
      stable bulk dispersions.
AB  - The competition between surface adsorption and bulk aggregation was investigated
      for silica colloids dispersed in cyclohexane in contact with hydrophobized silica
      substrates. Central to this study is that the colloids and surfaces have the same
      material and surface properties. Colloid-colloid and colloid-surface interactions
      were controlled by addition of polymers providing depletion interaction. Bulk
      instability was determined by turbidity and viscosity measurements and surface
      adsorption by ellipsometry measurements. At increasing polymer concentration,
      strong surface adsorption occurred at polymer concentrations below that required
      for bulk phase separation. Complementary Monte Carlo simulations with the use of
      a new weak depletion theory support quantitatively the experimental observation
      of the existence of an interval of interaction strength at which aggregation in
      bulk is negligible while surface adsorption is substantial.

PMID- 27025950
TI  - A Molecular Chipper technology for CRISPR sgRNA library generation and functional
      mapping of noncoding regions.
AB  - Clustered regularly-interspaced palindromic repeats (CRISPR)-based genetic
      screens using single-guide-RNA (sgRNA) libraries have proven powerful to identify
      genetic regulators. Applying CRISPR screens to interrogate functional elements in
      noncoding regions requires generating sgRNA libraries that are densely covering,
      and ideally inexpensive, easy to implement and flexible for customization. Here
      we present a Molecular Chipper technology for generating dense sgRNA libraries
      for genomic regions of interest, and a proof-of-principle screen that identifies
      novel cis-regulatory domains for miR-142 biogenesis. The Molecular Chipper
      approach utilizes a combination of random fragmentation and a type III
      restriction enzyme to derive a densely covering sgRNA library from input DNA.
      Applying this approach to 17 microRNAs and their flanking regions and with a
      reporter for miR-142 activity, we identify both the pre-miR-142 region and two
      previously unrecognized cis-domains important for miR-142 biogenesis, with the
      latter regulating miR-142 processing. This strategy will be useful for
      identifying functional noncoding elements in mammalian genomes. 

PMID- 27025951
TI  - Safety, efficacy and clinical generalization of the STAR protocol: a
      retrospective analysis.
AB  - BACKGROUND: The changes in metabolic pathways and metabolites due to critical
      illness result in a highly complex and dynamic metabolic state, making safe,
      effective management of hyperglycemia and hypoglycemia difficult. In addition,
      clinical practices can vary significantly, thus making GC protocols difficult to
      generalize across units.The aim of this study was to provide a retrospective
      analysis of the safety, performance and workload of the stochastic targeted
      (STAR) glycemic control (GC) protocol to demonstrate that patient-specific, safe,
      effective GC is possible with the STAR protocol and that it is also generalizable
      across/over different units and clinical practices. METHODS: Retrospective
      analysis of STAR GC in the Christchurch Hospital Intensive Care Unit (ICU), New
      Zealand (267 patients), and the Gyula Hospital, Hungary (47 patients), is
      analyzed (2011-2015). STAR Christchurch (BG target 4.4-8.0 mmol/L) is also
      compared to the Specialized Relative Insulin and Nutrition Tables (SPRINT)
      protocol (BG target 4.4-6.1 mmol/L) implemented in the Christchurch Hospital ICU,
      New Zealand (292 patients, 2005-2007). Cohort mortality, effectiveness and safety
      of glycemic control and nutrition delivered are compared using nonparametric
      statistics. RESULTS: Both STAR implementations and SPRINT resulted in over 86 %
      of time per episode in the blood glucose (BG) band of 4.4-8.0 mmol/L. Patients
      treated using STAR in Christchurch ICU spent 36.7 % less time on protocol and
      were fed significantly more than those treated with SPRINT (73 vs. 86 % of
      caloric target). The results from STAR in both Christchurch and Gyula were very
      similar, with the BG distributions being almost identical. STAR provided safe GC
      with very few patients experiencing severe hypoglycemia (BG < 2.2 mmol/L, <5
      patients, 1.5 %). CONCLUSIONS: STAR outperformed its predecessor, SPRINT, by
      providing higher nutrition and equally safe, effective control for all the days
      of patient stay, while lowering the number of measurements and interventions
      required. The STAR protocol has the ability to deliver high performance and high
      safety across patient types, time, clinical practice culture (Christchurch and
      Gyula) and clinical resources.

PMID- 27025952
TI  - Identification of S-glutathionylation sites in species-specific proteins by
      incorporating five sequence-derived features into the general pseudo-amino acid
      composition.
AB  - As a selective and reversible protein post-translational modification, S
      glutathionylation generates mixed disulfides between glutathione (GSH) and
      cysteine residues, and plays an important role in regulating protein activity,
      stability, and redox regulation. To fully understand S-glutathionylation
      mechanisms, identification of substrates and specific S-Glutathionylated sites is
      crucial. Experimental identification of S-glutathionylated sites is labor
      intensive and time consuming, so establishing an effective computational method
      is much desirable due to their convenient and fast speed. Therefore, in this
      study, a new bioinformatics tool named SSGlu (Species-Specific identification of
      Protein S-glutathionylation Sites) was developed to identify species-specific
      protein S-glutathionylated sites, utilizing support vector machines that combine
      multiple sequence-derived features with a two-step feature selection. By 5-fold
      cross validation, the performance of SSGlu was measured with an AUC of 0.8105 and
      0.8041 for Homo sapiens and Mus musculus, respectively. Additionally, SSGlu was
      compared with the existing methods, and the higher MCC and AUC of SSGlu
      demonstrated that SSGlu was very promising to predict S-glutathionylated sites.
      Furthermore, a site-specific analysis showed that S-glutathionylation intimately
      correlated with the features derived from its surrounding sites. The conclusions
      derived from this study might help to understand more of the S-glutathionylation
      mechanism and guide the related experimental validation. For public access, SSGlu
      is freely accessible at http://59.73.198.144:8080/SSGlu/.

PMID- 27025953
TI  - X-ray and magnetic resonance imaging fusion for cardiac resynchronization
      therapy.
AB  - Cardiac Resynchronization Therapy (CRT) can effectively treat left ventricle (LV)
      driven Heart Failure (HF). However, 30% of the CRT recipients do not experience
      symptomatic benefit. Recent studies show that the CRT response rate can reach 95%
      when the LV pacing lead is placed at an optimal site at a region of maximal LV
      dyssynchrony and away from myocardial scars. Cardiac Magnetic Resonance (CMR) can
      identify the optimal site in three dimensions (3D). 3D CMR data can be registered
      to clinical standard x-ray fluoroscopy to achieve an optimal pacing of the LV. We
      have developed a 3D CMR to 2D x-ray image registration method for CRT procedures.
      We have employed the LV pacing lead on x-ray images and coronary sinus on MR data
      as landmarks. The registration method makes use of a guidewire simulation
      algorithm, edge based image registration technique and x-ray C-arm tracking to
      register the coronary sinus and pacing lead landmarks. 

PMID- 27025954
TI  - Chemical Reactivity and Respiratory Toxicity of the alpha-Diketone Flavoring
      Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione.
AB  - Occupational exposure to 2,3-butanedione (BD) vapors has been associated with
      severe respiratory disease leading to the use of potentially toxic substitutes.
      We compared the reactivity and respiratory toxicity of BD with that of two
      structurally related substitutes, 2,3-pentanedione (PD) and 2,3-hexanedione (HD).
      Chemical reactivity of the diketones with an arginine substrate decreased with
      increasing chain length (BD > PD > HD). Animals were evaluated the morning after
      a 2-week exposure to 0, 100, 150, or 200 ppm BD, PD, or HD (postexposure) or 2
      weeks later (recovery). Bronchial fibrosis was observed in 5/5 BD and 5/5 PD rats
      at 200 ppm and in 4/6 BD and 6/6 PD rats at 150 ppm in the postexposure groups.
      Following recovery, bronchial fibrosis was observed in all surviving rats exposed
      to 200 ppm BD (5/5) or PD (3/3) and in 2/10 BD and 7/9 PD rats exposed to 150
      ppm. Bronchial fibrosis was observed only in 2/12 HD-exposed rats in the 200 ppm
      postexposure group. Patchy interstitial fibrosis affected lungs of recovery
      groups exposed to 200 ppm PD (3/3) or BD (1/5) and to 150 ppm PD (4/9) or BD
      (7/10) and correlated with pulmonary function deficits. BD and PD were more
      reactive and produced more bronchial fibrosis than HD.

PMID- 27025955
TI  - Aerosolized Silver Nanoparticles in the Rat Lung and Pulmonary Responses over
      Time.
AB  - Silver nanoparticle (Ag NP) production methods are being developed and refined to
      produce more uniform Ag NPs through chemical reactions involving silver salt
      solutions, solvents, and capping agents to control particle formation. These
      chemical reactants are often present as contaminants and/or coatings on the Ag
      NPs, which could alter their interactions in vivo. To determine pulmonary effects
      of citrate-coated Ag NPs, Sprague-Dawley rats were exposed once nose-only to
      aerosolized Ag NPs (20 nm [C20] or 110 nm [C110] Ag NPs) for 6 hr.
      Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, 21,
      and 56 days postexposure for analyses. Inhalation of Ag NPs, versus citrate
      buffer control, produced significant inflammatory and cytotoxic responses that
      were measured in BALF cells and supernatant. At day 7, total cells, protein, and
      lactate dehydrogenase were significantly elevated in BALF, and peak
      histopathology was noted after C20 or C110 exposure versus control. At day 21,
      BALF polymorphonuclear cells and tissue inflammation were significantly greater
      after C20 versus C110 exposure. By day 56, inflammation was resolved in Ag NP
      exposed animals. Overall, results suggest delayed, short-lived inflammatory and
      cytotoxic effects following C20 or C110 inhalation and potential for greater
      responses following C20 exposure.

PMID- 27025956
TI  - "War on drugs" has harmed public health and human rights, finds new analysis.

PMID- 27025957
TI  - An automated deformable image registration evaluation of confidence tool.
AB  - Deformable image registration (DIR) is a powerful tool for radiation oncology,
      but it can produce errors. Beyond this, DIR accuracy is not a fixed quantity and
      varies on a case-by-case basis. The purpose of this study is to explore the
      possibility of an automated program to create a patient- and voxel-specific
      evaluation of DIR accuracy. AUTODIRECT is a software tool that was developed to
      perform this evaluation for the application of a clinical DIR algorithm to a set
      of patient images. In brief, AUTODIRECT uses algorithms to generate deformations
      and applies them to these images (along with processing) to generate sets of test
      images, with known deformations that are similar to the actual ones and with
      realistic noise properties. The clinical DIR algorithm is applied to these test
      image sets (currently 4). From these tests, AUTODIRECT generates spatial and dose
      uncertainty estimates for each image voxel based on a Student's t distribution.
      In this study, four commercially available DIR algorithms were used to deform a
      dose distribution associated with a virtual pelvic phantom image set, and
      AUTODIRECT was used to generate dose uncertainty estimates for each deformation.
      The virtual phantom image set has a known ground-truth deformation, so the true
      dose-warping errors of the DIR algorithms were also known. AUTODIRECT predicted
      error patterns that closely matched the actual error spatial distribution. On
      average AUTODIRECT overestimated the magnitude of the dose errors, but tuning the
      AUTODIRECT algorithms should improve agreement. This proof-of-principle test
      demonstrates the potential for the AUTODIRECT algorithm as an empirical method to
      predict DIR errors. 

PMID- 27025958
TI  - Physical and Psychological Morbidity in Adolescents With Atypical Anorexia
      Nervosa.
AB  - BACKGROUND AND OBJECTIVE: Adolescents with atypical anorexia nervosa (AN) have
      lost significant weight but are not underweight. This study aimed to describe the
      physical and psychological morbidity of adolescents diagnosed with atypical AN,
      and to compare them with underweight adolescents with AN. METHODS: All first
      presentations of atypical AN (n = 42) and full-threshold AN (n = 118) to a
      specialist pediatric eating disorder program between July 2010 and June 2014 were
      examined. Diagnosis was assessed by using the Eating Disorder Examination and
      anthropometric measurement. Psychological morbidity measures included eating and
      weight concerns, bingeing, purging, compulsive exercise, and psychiatric
      comorbidity. RESULTS: Compared with AN, more adolescents with atypical AN were
      premorbidly overweight or obese (71% vs 12%). They had lost more weight (17.6 kg
      vs 11.0 kg) over a longer period (13.3 vs 10.2 months). There was no significant
      difference in the frequency of bradycardia (24% vs 33%;) or orthostatic
      instability (43% vs 38%). We found no evidence of a difference in frequency of
      psychiatric comorbidities (38% vs 45%) or suicidal ideation (43% vs 39%).
      Distress related to eating and body image was more severe in atypical AN.
      CONCLUSIONS: Atypical AN considerably affects physical and psychological
      functioning, despite adolescents presenting within or above the normal weight
      range. There was little evidence that the morbidity of adolescents with atypical
      AN was any less severe than that of adolescents with full-threshold AN. The
      findings support the need for vigilance around weight loss in adolescents,
      regardless of body size.

PMID- 27025959
TI  - Cases of Psychiatric Morbidity in Pediatric Patients After Remission of Cushing
      Syndrome.
AB  - Endogenous Cushing syndrome (CS) may have different effects in children than what
      has been described in adults. Previous studies of children and adolescents with
      CS have identified cognitive decline despite reversal of brain atrophy after
      remission of CS. Although the observations of parents of children and adolescents
      with CS support personality changes, significant psychopathology has not been
      described in the literature. We report 9 children who underwent successful
      surgery (transsphenoidal surgery [TSS] or resection of bronchial carcinoid) for
      treatment of CS and subsequently developed significant affective pathology.
      Affective symptoms included anger-rage outbursts, suicidal ideation,
      irritability, anxiety, and depression. One child, who committed suicide 60 months
      after TSS, had recently discontinued antidepressant medication. She had a history
      of anxiety during active CS and was treated with an anxiolytic. The 7 patients
      with onset of symptoms within 7 months of TSS were on glucocorticoid replacement,
      and 1-year follow-up evaluation showed recovery of hypothalamic-pituitary-adrenal
      axis and biochemical evidence of remission. The 2 patients who presented with
      onset of symptoms at 48 months or later underwent endocrine evaluation that
      showed biochemical evidence of remission and normal anterior pituitary hormone
      levels. This is the first report of affective symptoms and behavioral
      dysregulation, including suicidal ideation, in a subgroup of children and
      adolescents after remission of CS. Health care providers caring for children with
      CS who have been cured should continue to screen for mental illness, monitor for
      changes in behavior, and refer as appropriate to mental health professionals. 

PMID- 27025960
TI  - Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected
      Infants.
AB  - BACKGROUND: Increased morbidity and mortality from lower respiratory tract
      infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children;
      however, the contribution of respiratory viruses is unclear. We studied the
      epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU
      infants aged <6 months in South Africa. METHODS: We prospectively enrolled
      hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using
      polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses
      and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site
      with population denominators. RESULTS: We enrolled 3537 children aged <6 months.
      HIV infection and exposure status were determined for 2507 (71%), of whom 211
      (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual
      incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95%
      confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5),
      compared with HUU infants. Relative incidence estimates were greater in HEU than
      HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human
      metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend
      observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those
      with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and
      12.2, 95% CI 1.7-infinity, respectively) of death than HUU. CONCLUSIONS: HEU
      infants were more likely to be hospitalized and to die in-hospital than HUU,
      including specifically due to RSV. This group should be considered a high-risk
      group for LRTI.

PMID- 27025961
TI  - Immobilized epidermal growth factor stimulates persistent, directed keratinocyte
      migration via activation of PLCgamma1.
AB  - Epidermal growth factor (EGF) is a critical element in dermal repair, but EGF
      containing wound dressings have not been successful clinically. However, these
      dressings have delivered only soluble EGF, and the native environment provides
      both soluble and matrix-bound EGF. To address our hypothesis that tethered EGF
      can stimulate cell behaviors not achievable with soluble EGF, we examined single
      cell movement and signaling in human immortalized HaCaT keratinocytes treated
      with soluble or immobilized EGF. Although both EGF treatments increased
      collective sheet displacement and individual cell speed, only cells treated with
      immobilized EGF exhibited directed migration, as well as 2-fold greater
      persistence compared with soluble EGF. Immunofluorescence showed altered EGF
      receptor (EGFR) trafficking, where EGFR remained membrane-localized in the
      immobilized EGF condition. Cells treated with soluble EGF demonstrated higher
      phosphorylated ERK1/2, and cells on immobilized EGF exhibited higher pPLCgamma1,
      which was localized at the leading edge. Treatment with U0126 inhibited migration
      in both conditions, demonstrating that ERK1/2 activity was necessary but not
      responsible for the observed differences. In contrast, PLCgamma1 inhibition with
      U73122 significantly decreased persistence on immobilized EGF. Combined, these
      results suggest that immobilized EGF increases collective keratinocyte
      displacement via an increase in single-cell migration persistence resulting from
      altered EGFR trafficking and PLCgamma1 activation.-Kim, C. S., Mitchell, I. P.,
      Desotell, A. W., Kreeger, P. K., Masters, K. S. Immobilized epidermal growth
      factor stimulates persistent, directed keratinocyte migration via activation of
      PLCgamma1.

PMID- 27025962
TI  - Dissociated sterol-based liver X receptor agonists as therapeutics for chronic
      inflammatory diseases.
AB  - Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of
      immune responses. Activation of LXR-mediated transcription by synthetic agonists,
      such as T0901317 and GW3965, attenuates progression of inflammatory disease in
      animal models. However, the adverse effects of these conventional LXR agonists in
      elevating liver lipids have impeded exploitation of this intriguing mechanism for
      chronic therapy. Here, we explore the ability of a series of sterol-based LXR
      agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We
      show that oral treatment with sterol-based LXR agonists in mice significantly
      reduces dextran sulfate sodium colitis-induced body weight loss, which is
      accompanied by reduced expression of inflammatory markers in the large intestine.
      The anti-inflammatory property of these agonists is recapitulated in vitro in
      mouse lamina propria mononuclear cells, human colonic epithelial cells, and human
      peripheral blood mononuclear cells. In addition, treatment with LXR agonists
      dramatically suppresses inflammatory cytokine expression in a model of traumatic
      brain injury. Importantly, in both disease models, the sterol-based agonists do
      not affect the liver, and the conventional agonist T0901317 results in
      significant liver lipid accumulation and injury. Overall, these results provide
      evidence for the development of sterol-based LXR agonists as novel therapeutics
      for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng,
      B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay,
      M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic
      inflammatory diseases.

PMID- 27025964
TI  - Predicting microbial interactions through computational approaches.
AB  - Microorganisms play a vital role in various ecosystems and characterizing
      interactions between them is an essential step towards understanding the
      organization and function of microbial communities. Computational prediction has
      recently become a widely used approach to investigate microbial interactions. We
      provide a thorough review of emerging computational methods organized by the type
      of data they employ. We highlight three major challenges in inferring
      interactions using metagenomic survey data and discuss the underlying assumptions
      and mathematics of interaction inference algorithms. In addition, we review
      interaction prediction methods relying on metabolic pathways, which are
      increasingly used to reveal mechanisms of interactions. Furthermore, we also
      emphasize the importance of mining the scientific literature for microbial
      interactions - a largely overlooked data source for experimentally validated
      interactions.

PMID- 27025963
TI  - Neuronal Wiskott-Aldrich syndrome protein regulates TGF-beta1-mediated lung
      vascular permeability.
AB  - TGF-beta1 induces an increase in paracellular permeability and actin stress fiber
      formation in lung microvascular endothelial and alveolar epithelial cells via
      small Rho GTPase. The molecular mechanism involved is not fully understood.
      Neuronal Wiskott-Aldrich syndrome protein (N-WASP) has an essential role in actin
      structure dynamics. We hypothesized that N-WASP plays a critical role in these
      TGF-beta1-induced responses. In these cell monolayers, we demonstrated that N
      WASP down-regulation by short hairpin RNA prevented TGF-beta1-mediated disruption
      of the cortical actin structure, actin stress filament formation, and increased
      permeability. Furthermore, N-WASP down-regulation blocked TGF-beta1 activation
      mediated by IL-1beta in alveolar epithelial cells, which requires actin stress
      fiber formation. Control short hairpin RNA had no effect on these TGF-beta1
      induced responses. TGF-beta1-induced phosphorylation of Y256 of N-WASP via
      activation of small Rho GTPase and focal adhesion kinase mediates TGF-beta1
      induced paracellular permeability and actin cytoskeleton dynamics. In vivo,
      compared with controls, N-WASP down-regulation increases survival and prevents
      lung edema in mice induced by bleomycin exposure-a lung injury model in which TGF
      beta1 plays a critical role. Our data indicate that N-WASP plays a crucial role
      in the development of TGF-beta1-mediated acute lung injury by promoting pulmonary
      edema via regulation of actin cytoskeleton dynamics.-Wagener, B. M., Hu, M.,
      Zheng, A., Zhao, X., Che, P., Brandon, A., Anjum, N., Snapper, S., Creighton, J.,
      Guan, J.-L., Han, Q., Cai, G.-Q., Han, X., Pittet, J.-F., Ding, Q. Neuronal
      Wiskott-Aldrich syndrome protein regulates TGF-beta1-mediated lung vascular
      permeability.

PMID- 27025965
TI  - Pitfalls in assessing microvascular endothelial barrier function: impedance-based
      devices versus the classic macromolecular tracer assay.
AB  - The most frequently used parameters to describe the barrier properties of
      endothelial cells (ECs) in vitro are (i) the macromolecular permeability,
      indicating the flux of a macromolecular tracer across the endothelium, and (ii)
      electrical impedance of ECs grown on gold-film electrodes reporting on the cell
      layer's tightness for ion flow. Due to the experimental differences between these
      approaches, inconsistent observations have been described. Here, we present the
      first direct comparison of these assays applied to one single cell type (human
      microvascular ECs) under the same experimental conditions. The impact of
      different pharmacological tools (histamine, forskolin, Y-27632, blebbistatin,
      TRAP) on endothelial barrier function was analyzed by Transwell((r)) tracer
      assays and two commercial impedance devices (xCELLigence((r)), ECIS((r))). The
      two impedance techniques provided very similar results for all compounds, whereas
      macromolecular permeability readings were found to be partly inconsistent with
      impedance. Possible reasons for these discrepancies are discussed. We conclude
      that the complementary combination of both approaches is highly recommended to
      overcome the restrictions of each assay. Since the nature of the growth support
      may contribute to the observed differences, structure-function relationships
      should be based on cells that are consistently grown on either permeable or
      impermeable growth supports in all experiments. 

PMID- 27025966
TI  - Influence of genetic polymorphisms of multidrug and toxin extrusion protein 1 on
      its mRNA expression in peripheral blood cells.
AB  - This study aimed to determine the effect of multidrug and toxin extrusion protein
      1 (MATE1) genetic variants on its transcript expression in peripheral blood
      cells. Consistent with previous in vitro findings, MATE1 mRNA levels were
      significantly higher in subjects carrying rs2453579, but not rs2252281, compared
      to those without either of these promoter variants. In addition, the mRNA levels
      did not differ between subjects with both variants and those with neither allele.
      Thus, this study reveals that the influence of MATE1 genetic variants on its mRNA
      expression can be detected in vivo using peripheral blood. 

PMID- 27025967
TI  - Prohibitin 1 regulates tumor cell apoptosis via the interaction with X-linked
      inhibitor of apoptosis protein.

PMID- 27025968
TI  - Prevalence of Masked Hypertension and Its Association With Subclinical
      Cardiovascular Disease in African Americans: Results From the Jackson Heart
      Study.
AB  - BACKGROUND: Studies consisting mostly of whites have shown that the prevalence of
      masked hypertension differs by prehypertension status. Using data from the
      Jackson Heart Study, an exclusively African American population-based cohort, we
      evaluated the association of masked hypertension and prehypertension with left
      ventricular mass index and common carotid intima media thickness. METHODS AND
      RESULTS: At the baseline visit, clinic blood pressure (CBP) measurement and 24
      hour ambulatory blood pressure monitoring were performed. Masked hypertension was
      defined as mean systolic/diastolic CBP <140/90 mm Hg and mean daytime
      systolic/diastolic ambulatory blood pressure >=135/85 mm Hg. Clinic hypertension
      was defined as mean systolic/diastolic CBP >=140/90 mm Hg. Normal CBP was defined
      as mean systolic/diastolic CBP <120/80 mm Hg and prehypertension as mean
      systolic/diastolic CBP 120 to 139/80 to 89 mm Hg. The analytic sample included
      909 participants. Among participants with systolic/diastolic CBP <140/90 mm Hg,
      the prevalence of masked hypertension and prehypertension was 27.5% and 62.4%,
      respectively. The prevalence of masked hypertension among those with normal CBP
      and prehypertension was 12.9% and 36.3%, respectively. In a fully adjusted model,
      which included prehypertension status and antihypertensive medication use as
      covariates, left ventricular mass index was 7.94 g/m(2) lower among those without
      masked hypertension compared to participants with masked hypertension (P<0.001).
      Left ventricular mass index was also 4.77 g/m(2) lower among those with clinic
      hypertension, but this difference was not statistically significant (P=0.068).
      There were no significant differences in left ventricular mass index between
      participants with and without masked hypertension, or clinic hypertension.
      CONCLUSIONS: Masked hypertension was common among African Americans with
      prehypertension and also normal CBP, and was associated with subclinical
      cardiovascular disease.

PMID- 27025969
TI  - Comparative Effectiveness of Personalized Lifestyle Management Strategies for
      Cardiovascular Disease Risk Reduction.
AB  - BACKGROUND: Evidence shows that healthy diet, exercise, smoking interventions,
      and stress reduction reduce cardiovascular disease risk. We aimed to compare the
      effectiveness of these lifestyle interventions for individual risk profiles and
      determine their rank order in reducing 10-year cardiovascular disease risk.
      METHODS AND RESULTS: We computed risks using the American College of
      Cardiology/American Heart Association Pooled Cohort Equations for a variety of
      individual profiles. Using published literature on risk factor reductions through
      diverse lifestyle interventions-group therapy for stopping smoking, Mediterranean
      diet, aerobic exercise (walking), and yoga-we calculated the risk reduction
      through each of these interventions to determine the strategy associated with the
      maximum benefit for each profile. Sensitivity analyses were conducted to test the
      robustness of the results. In the base-case analysis, yoga was associated with
      the largest 10-year cardiovascular disease risk reductions (maximum absolute
      reduction 16.7% for the highest-risk individuals). Walking generally ranked
      second (max 11.4%), followed by Mediterranean diet (max 9.2%), and group therapy
      for smoking (max 1.6%). If the individual was a current smoker and successfully
      quit smoking (ie, achieved complete smoking cessation), then stopping smoking
      yielded the largest reduction. Probabilistic and 1-way sensitivity analysis
      confirmed the demonstrated trend. CONCLUSIONS: This study reports the comparative
      effectiveness of several forms of lifestyle modifications and found smoking
      cessation and yoga to be the most effective forms of cardiovascular disease
      prevention. Future research should focus on patient adherence to personalized
      therapies, cost-effectiveness of these strategies, and the potential for enhanced
      benefit when interventions are performed simultaneously rather than as single
      measures.

PMID- 27025970
TI  - Identification of PTCSC3 as a Novel Locus for Large-Vessel Ischemic Stroke: A
      Genome-Wide Association Study.
AB  - BACKGROUND: Ischemic stroke is a major cause of death and disability in the
      world. A major ischemic stroke subtype, large-vessel ischemic stroke (large
      artery atherosclerosis; LAA), has been shown to have some genetic components in
      individuals of European ancestry. However, it is not clear whether the genetic
      predisposition to LAA stroke varies among ethnicities. We sought to identify
      genetic factors that contribute to LAA stroke in 2 independent samples of Han
      Chinese individuals. METHODS AND RESULTS: Novel genetic variants that predispose
      individuals to LAA stroke were identified using a genome-wide association study
      (GWAS) of 444 individuals with LAA stroke and 1727 controls in a Han Chinese
      population residing in Taiwan. The study was replicated in an independent Han
      Chinese population comprising an additional 319 cases and 1802 controls. We
      identified 5 single-nucleotide polymorphisms, including rs2415317 (P=3.10*10(
      8)), rs934075 (P=4.00*10(-9)), rs944289 (P=3.57*10(-8)), rs2787417 (P=1.76*10(
      8)), and rs1952706 (P=2.92*10(-8)), at one novel locus on chromosome 14q13.3
      within PTCSC3 (encoding papillary thyroid carcinoma susceptibility candidate 3)
      that were associated with LAA stroke at genome-wide significance (P<5*10(-8)).
      CONCLUSIONS: Our data provide strong support for future studies on the role of
      PTCSC3 in the pathogenesis of LAA stroke and the association between LAA stroke
      development and thyroid function. In addition, these findings provide insights
      into the genetic basis of LAA stroke and identify a novel pathway that might be
      applicable for future therapeutic intervention.

PMID- 27025971
TI  - Masked Hypertension: An Independent Cardiovascular Risk Factor or a Facet of True
      Blood Pressure Level?

PMID- 27025972
TI  - Expression of 11beta-hydroxysteroid-dehydrogenase type 2 in human thymus.
AB  - 11beta-hydroxysteroid-dehydrogenase type 2 (11beta-HSD2) is a high affinity
      dehydrogenase which rapidly inactivates physiologically-active glucocorticoids to
      protect key tissues. 11beta-HSD2 expression has been described in peripheral
      cells of the innate and the adaptive immune system as well as in murine thymus.
      In absence of knowledge of 11beta-HSD2 expression in human thymus, the study
      aimed to localize 11beta-HSD2 in human thymic tissue. Thymic tissue was taken of
      six healthy, non-immunologically impaired male infants below 12months of age with
      congenital heart defects who had to undergo correction surgery. 11beta-HSD2
      protein expression was analyzed by immunohistochemistry and Western blot. Kidney
      tissue, peripheral blood mononuclear cells (PBMCs) and human umbilical vein
      endothelial cells (HUVEC) were taken as positive controls. Significant expression
      of 11beta-HSD2 protein was found at single cell level in thymus parenchyma, at
      perivascular sites of capillaries and small vessels penetrating the thymus lobuli
      and within Hassall's bodies. The present study demonstrates that 11beta-HSD2 is
      expressed in human thymus with predominant perivascular expression and also
      within Hassall's bodies. To our knowledge, this is the first report confirming
      11beta-HSD2 expression at the protein level in human thymic tissue underlining a
      potential role of this enzyme in regulating glucocorticoid function at the thymic
      level.

PMID- 27025973
TI  - Biotransformation of dehydro-epi-androsterone by Aspergillus parasiticus:
      Metabolic evidences of BVMO activity.
AB  - The research on the synthesis of steroids and its derivatives is of high interest
      due to their clinical applications. A particular focus is given to molecules
      bearing a D-ring lactone like testolactone because of its bioactivity. The
      Aspergillus genus has been used to perform steroid biotransformations since it
      offers a toolbox of redox enzymes. In this work, the use of growing cells of
      Aspergillus parasiticus to study the bioconversion of dehydro-epi-androsterone
      (DHEA) is described, emphasizing the metabolic steps leading to D-ring
      lactonization products. It was observed that A. parasiticus is not only capable
      of transforming bicyclo[3.2.0]hept-2-en-6-one, the standard Baeyer-Villiger
      monooxygenase (BVMO) substrate, but also yielded testololactone and the homo
      lactone 3beta-hydroxy-17a-oxa-D-homoandrost-5-en-17-one from DHEA. Moreover, the
      biocatalyst degraded the lateral chain of cortisone by an oxidative route
      suggesting the action of a BVMO, thus providing enough metabolic evidences
      denoting the presence of BVMO activity in A. parasiticus. Furthermore, since
      excellent biotransformation rates were observed, A. parasiticus is a promising
      candidate for the production of bioactive lactone-based compounds of steroidal
      origin in larger scales.

PMID- 27025974
TI  - From the alpha to the omega-3: Breaking the link between impaired fetal growth
      and adult cardiovascular disease.
AB  - Atherosclerotic vascular disease is an important cause of premature morbidity and
      mortality. An extensive body of epidemiologic data links impaired fetal growth,
      evidenced by reductions in birth weight, with a higher risk for cardiovascular
      disease in adulthood. This association appears to be at least partially
      independent of established cardiovascular risk factors, such as hypertension and
      type 2 diabetes. There is currently no clinically established strategy to prevent
      cardiovascular events secondary to being born with poor fetal growth. This review
      summarizes recent evidence that suggests that omega-3 polyunsaturated fatty acids
      may be beneficial for this indication; in particular being associated with more
      marked reductions in blood pressure and subclinical atherosclerosis in people who
      were born with poor fetal growth, than in those with healthy birth weight.
      Possible mechanisms, and the evidence base required to support the implementation
      of dietary guidelines specific to people born with impaired fetal growth are also
      described. 

PMID- 27025975
TI  - The lymph node neutrophil.
AB  - Secondary lymphoid organs provide a specialized microenvironment tailored to
      foster communication between cells of the innate and adaptive immune systems.
      These interactions allow immune cells to coordinate multilayered defense against
      pathogens. Until recently dendritic cells and macrophages were thought to
      comprise the main innate immune cell subsets responsible for delivering signals
      that drive the adaptive immune response, while the function of neutrophils was
      largely confined to the innate immune system. However, the discovery of
      neutrophils in lymph nodes has raised the question of whether neutrophils might
      play a more extensive role not only in innate immunity per se, but also in
      coordinating the interactions between innate and adaptive immune responses. In
      this review we discuss the mechanisms and consequences of neutrophil recruitment
      to lymph nodes and how this recruitment influences subsequent immune responses
      both in situ and at distant sites.

PMID- 27025976
TI  - Darier's Disease Complicated by Schizophrenia Caused by a Novel ATP2A2 Mutation.

PMID- 27025977
TI  - Poverty and working status in changes of unmet health care need in old age.
AB  - This study examined relationships between socioeconomic disadvantage and unmet
      health care needs among older adults in Korea adjusting for predisposing and
      health need factors. We examined how older adults' low-income status and working
      status affect unmet needs for healthcare over time, and how the association
      varies by reason for unmet needs (i.e. financial or non-financial). We used three
      waves of data (2009, 2011, 2012) from the Korea Health Panel (KHP) survey and a
      multinomial logistic mixed model to analyze how low socioeconomic disadvantages
      affects changes in unmet healthcare needs independently and in combination.
      Results showed that near-poor elders were more likely to experience increased
      risk of unmet need due to non-financial constraints over time. When working, near
      poor elders risk of unmet healthcare needs due to financial and non-financial
      factors increases substantially over time. Across societies, different subgroups
      of older adults may be at risk of unmet healthcare needs, contingent on
      healthcare policies. Our finding suggests that in Korea, near-poor working elders
      are the vulnerable subgroup at highest risk of unmet healthcare needs. This
      finding provides much-needed evidence of heterogeneity of vulnerability in unmet
      healthcare needs and can be used to design more affordable and accessible
      programs and services for this group. 

PMID- 27025978
TI  - Management and Outcomes of Isolated Tentorial and Parafalcine "Smear" Subdural
      Hematomas at a Level-1 Trauma Center: Necessity of High Acuity Care.
AB  - Data suggest that patients who present to trauma centers with mild traumatic
      brain injury (TBI) are admitted to an excessively high level of care and undergo
      myriad, unnecessary repeat radiographic and laboratory tests that do not affect
      outcome. Surprisingly, a paucity of data exists regarding the management of
      isolated, traumatic, parafalcine, or tentorial acute subdural hematoma (aSDH).
      Therefore, a retrospective, cohort study was completed to analyze factors
      associated with outcomes in patients who present to a high-volume, urban, level 1
      trauma center with isolated parafalcine or tentorial aSDH after closed head
      injury. Out of 3097 patients admitted with TBI over the study period, 65 met
      inclusion criteria. More than 90% of patients were admitted to the intensive care
      unit (ICU), irrespective of Glasgow Coma Scale (GCS) score at presentation or the
      presence of systemic injury. Factors determined to be statistically associated
      with increased ICU and total length of stay were GCS <= 12 on presentation and
      presence of systemic injury. Depressed GCS, systemic injury, and being elderly
      were associated with poor discharge disposition; whereas being systemically
      injured, female, or elderly were associated with poor functional status at
      discharge. Although 94% of admitted patients underwent at least one repeat head
      computed tomography (CT) scan while hospitalized, not a single aSDH enlarged,
      including four patients on antiplatelet agents, anticoagulants, or both. Based on
      these data, young patients who present with GCS 13-15 without systemic injury
      following blunt trauma with an associated isolated parafalcine and tentorial aSDH
      may be safely admitted to a standard medical/surgical floor for observation.

PMID- 27025980
TI  - Research and Evaluations of the Health Aspects of Disasters, Part VIII: Risk,
      Risk Reduction, Risk Management, and Capacity Building.
AB  - There is a cascade of risks associated with a hazard evolving into a disaster
      that consists of the risk that: (1) a hazard will produce an event; (2) an event
      will cause structural damage; (3) structural damage will create functional
      damages and needs; (4) needs will create an emergency (require use of the local
      response capacity); and (5) the needs will overwhelm the local response capacity
      and result in a disaster (ie, the need for outside assistance). Each step along
      the continuum/cascade can be characterized by its probability of occurrence and
      the probability of possible consequences of its occurrence, and each risk is
      dependent upon the preceding occurrence in the progression from a hazard to a
      disaster. Risk-reduction measures are interventions (actions) that can be
      implemented to: (1) decrease the risk that a hazard will manifest as an event;
      (2) decrease the amounts of structural and functional damages that will result
      from the event; and/or (3) increase the ability to cope with the damage and
      respond to the needs that result from an event. Capacity building increases the
      level of resilience by augmenting the absorbing and/or buffering and/or response
      capacities of a community-at-risk. Risks for some hazards vary by the context in
      which they exist and by the Societal System(s) involved. Birnbaum ML , Loretti A
      , Daily EK , O'Rourke AP . Research and evaluations of the health aspects of
      disasters, part VIII: risk, risk reduction, risk management, and capacity
      building. Prehosp Disaster Med. 2016;31(3):300-308. 

PMID- 27025979
TI  - Prefoldin and Pins synergistically regulate asymmetric division and suppress
      dedifferentiation.
AB  - Prefoldin is a molecular chaperone complex that regulates tubulin function in
      mitosis. Here, we show that Prefoldin depletion results in disruption of
      neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval
      brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteable
      (Pins) leads to the formation of gigantic brains with severe neuroblast
      overgrowth, despite that Pins depletion alone results in smaller brains with
      partially disrupted neuroblast polarity. We show that Prefoldin acts
      synergistically with Pins to regulate asymmetric division of both neuroblasts and
      Intermediate Neural Progenitors (INPs). Surprisingly, co-depletion of Prefoldin
      and Pins also induces dedifferentiation of INPs back into neuroblasts, while
      depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore,
      knocking down either alpha-tubulin or beta-tubulin in pins(-) mutant background
      results in INP dedifferentiation back into neuroblasts, leading to the formation
      of ectopic neuroblasts. Overexpression of alpha-tubulin suppresses neuroblast
      overgrowth observed in prefoldin pins double mutant brains. Our data elucidate an
      unexpected function of Prefoldin and Pins in synergistically suppressing
      dedifferentiation of INPs back into neural stem cells. 

PMID- 27025981
TI  - Evaluating the Role of the Air-Solution Interface on the Mechanism of Subvisible
      Particle Formation Caused by Mechanical Agitation for an IgG1 mAb.
AB  - Mechanical agitation of monoclonal antibody (mAb) solutions often leads to
      protein particle formation. In this study, various formulations of an
      immunoglobulin G (IgG) 1 mAb were subjected to different controlled interfacial
      stresses using a Langmuir trough, and protein particles formed at the interface
      and measured in bulk solution were characterized using atomic force microscopy
      and flow digital imaging. Results were compared to mAb solutions agitated in
      glass vials and unstressed controls. At lower pH, mAb solutions exhibited larger
      hysteresis in their surface pressure versus area isotherms and increased number
      of particles in bulk solution, when subjected to interfacial stresses. mAb
      samples subjected to 750-1000 interfacial compression-expansion cycles in 6 h
      contained high particle numbers in bulk solution, and displayed similar
      particulation trends when agitated in vials. At compression rates of 50 cycles in
      6 h, however, particle levels in mAb solutions were comparable to unstressed
      controls, despite protein aggregates being present at the air-solution interface.
      These results suggest that while the air-solution interface serves as a
      nucleation site for initiating protein aggregation, the number of protein
      particles measured in bulk mAb solutions depends on the total number of
      compression cycles that proteins at the air-solution interface are subjected to
      within a fixed time.

PMID- 27025982
TI  - Effect of Absorption Behavior of Solubilizers on Drug Dissolution in the
      Gastrointestinal Tract: Evaluation Based on In Vivo Luminal Concentration-Time
      Profile of Cilostazol, a Poorly Soluble Drug, and Solubilizers.
AB  - The purpose of this study was to evaluate the effect of absorption behavior of
      solubilizers on drug dissolution in the gastrointestinal tract. After oral
      administration of FITC-dextran (FD-10), a nonabsorbable marker, and cilostazol
      (CZ), a low-solubility drug, with or without solubilizers (dimethyl sulfoxide
      [DMSO], and d-alpha-tocopherol polyethylene glycol 1000 succinate [TPGS]), the in
      vivo rat luminal concentrations of these compounds were determined by direct
      sampling of residual water in each segment of the gastrointestinal tract. DMSO
      was rapidly absorbed and not detected in the middle small intestine. Conversely,
      the TPGS concentration increased by 1.5- and 2-fold relative to the initial dose
      concentration in the middle and lower small intestine, respectively, owing to
      condensation. Then, normalized area under the luminal concentration-time curve of
      solid CZ was calculated from the luminal concentration-time profiles of FD-10 and
      solid CZ to evaluate in vivo dissolution behavior of CZ. The dissolution of CZ
      was marked when administered with TPGS compared with that when administered with
      DMSO, especially in the lower small intestine. This clearly indicates that
      absorbability of solubilizers is one of the important factors in determining the
      solubilizing effect. These findings may be beneficial to development of oral
      lipophilic drugs.

PMID- 27025983
TI  - Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1
      and 1A9 alters their quercetin glucuronidation activities.
AB  - Uridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug
      metabolism enzyme superfamily involved in the glucuronidation of endobiotics and
      xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit
      or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type
      and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes,
      UGT1A9*2(C3Y), UGT1A9*3(M33T), and UGT1A9*5(D256N) were single- or double
      expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9
      allozymes was observed via fluorescence resonance energy transfer (FRET) and co
      immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein
      protein interaction, resulting in differential FRET efficiencies and donor
      acceptor r distances. Dimerization changed the chemical regioselectivity,
      substrate-binding affinity, and enzymatic activity of UGT1A1 and UGT1A9 in
      glucuronidation of quercetin. These findings provide molecular insights into the
      consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes
      expression on quercetin glucuronidation. 

PMID- 27025984
TI  - How formative courses about damage control surgery and non-operative management
      improved outcome and survival in unstable politrauma patients in a Mountain
      Trauma Center.
AB  - AIM: Aim of this study is to analyze how the starting of Course of Trauma in our
      hospital improved survival and organization in management of polytraumatized
      patients. MATERIAL OF STUDY: We analysed all major trauma patients (Injury
      Severity Score (Injury Severity Score (ISS)> 15) treated at Emergency Department
      of the Santa Chiara Hospital between January 2011 and December 2014. The training
      courses (TC) were named "management of polytrauma" (MP) and "clinical cases
      discussion" (CCD), and started in November 2013. We divided the patients between
      two groups: before November 2013 (pre-TC group) and after November 2013 (post-TC
      group). RESULTS: MTG's courses (EMC accredited), CCD and MP courses started in
      November 2013. The target of these courses was the multidisciplinary management
      of polytrauma patient; the courses were addressed to general surgeons,
      anaesthesiologists, radiologists, orthopaedics and emergency physicians.
      Respectively 110 and 78 doctors were formed in CCD's and MP's courses. Patients
      directly transported to our trauma centre rose from 67.5% to 83% (p<0,005), and E
      FAST grew from 15.6% in the pre-TC group to 51.3% in the post-TC group. Time of
      access in operatory theatre decreased from 62 to 44 minutes. Early Mortality
      (within 48 hours from the hospital arrival) was 9% in the pre-TC group and 4.5%
      in the post-tc group (p<0.005). DISCUSSION: Be needed to complete our goal.
      Further analysis and possible comparison with other trauma centers be needed to
      complete our goal CONCLUSIONS: Our results show that in our experience the
      multidisciplinary approach to polytrauma patients increased early survival and
      improved outcome with an evidence of worker's satisfaction. However, the best
      practice would ask to start with the approval of procedures and guidelines by the
      hospital governance, followed by clinical practice changes, in order to create a
      dedicated emergency and trauma surgery group. KEY WORD: Damage Control Surgery,
      Non Operative Management, Trauma Course, Trauma Team, Trauma Center.

PMID- 27025985
TI  - Using the NIATx Model to Implement User-Centered Design of Technology for Older
      Adults.
AB  - What models can effectively guide the creation of eHealth and mHealth
      technologies? This paper describes the use of the NIATx model as a framework for
      the user-centered design of a new technology for older adults. The NIATx model is
      a simple framework of process improvement based on the following principles
      derived from an analysis of decades of research from various industries about why
      some projects fail and others succeed: (1) Understand and involve the customer;
      (2) fix key problems; (3) pick an influential change leader; (4) get ideas from
      outside the field; (5) use rapid-cycle testing. This paper describes the use of
      these principles in technology development, the strengths and challenges of using
      this approach in this context, and lessons learned from the process. Overall, the
      NIATx model enabled us to produce a user-focused technology that the anecdotal
      evidence available so far suggests is engaging and useful to older adults. The
      first and fourth principles were especially important in developing the
      technology; the fourth proved the most challenging to use. 

PMID- 27025986
TI  - Evaluation of the durability of pain relief throughout a 12 hour dosing interval
      of a novel, extended-release, abuse-deterrent formulation of oxycodone.
AB  - BACKGROUND: Abuse deterrent formulations (ADF) are designed to prevent the misuse
      of opioids by tampering (e.g. physical and chemical manipulation) in order to
      ingest the opioid in a manner other than intended. Extended-release (ER)
      formulations are formulated with a larger drug load than immediate-release (IR)
      formulations, which makes ER opioids more desirable to drug abusers than I.R.
      formulations. ADFs, therefore, are particularly useful with ER opioid agents,
      which are designed to produce consistent analgesia over prolonged dosing
      intervals. However, the drug release properties of these formulations vary and
      sometimes may not provide adequate pain relief throughout the intended dosing
      interval, requiring patients to take additional medication for pain relief.
      Oxycodone DETERx* (Xtampza ER * ) is a novel, microsphere-in-capsule opioid
      formulation, which allows for twice daily dosing (i.e. every 12 hours) and
      mitigates the ability to tamper with the formulation. OBJECTIVE: To evaluate the
      durability of pain relief of a novel formulation of oxycodone throughout the 12
      hour dosing interval. RESEARCH DESIGN AND METHODS: This study is a post-hoc
      analysis of 193 subjects in a Phase 3 randomized withdrawal, double-blind,
      placebo-controlled, enriched-enrollment, parallel-group, multicenter, 12-week
      clinical study. MAIN OUTCOME MEASURES: The analysis evaluated the frequency and
      distribution of use of oxycodone ER and rescue medication during the Double-blind
      Maintenance Phase of the study. RESULTS: Usage patterns captured by an electronic
      diary indicated limited overall and limited per-day use of rescue medication with
      no increase in rescue medication consumption 8 to 12 hours post-dose, suggesting
      that subjects did not experience end-of-dose failure during this time period.
      LIMITATIONS: This study is limited in that it is a post-hoc analysis based on
      data gathered electronically from a large, prospective, double-blind, randomized,
      placebo-controlled, Phase 3 clinical study. CONCLUSION: The evaluation of dosing
      patterns indicates that this ER oxycodone capsule formulation has durability of
      effect over the entire 12-hour dosing interval. These data support the use of
      abuse-deterrent oxycodone ER as a 12-hour dosing formulation.

PMID- 27025987
TI  - The correlation between radiographic and pathologic grading of lumbar facet joint
      degeneration.
AB  - BACKGROUND: Before performing spine non-fusion surgery that retains the facet
      joints, choosing an accurate radiographic method to evaluate the degree of facet
      joint degeneration is extremely important. Therefore, the objective of this study
      was to determine the accuracy and reliability of different radiographic
      classifications by analyzing the correlation between radiographic and pathologic
      grading of lumbar facet joint degeneration. Taking the pathologic examination as
      standard, the consistency of computed tomography (CT) and magnetic resonance
      imaging (MRI) assessment of lumbar facet joint degeneration was compared.
      METHODS: A total of 74 facet joints obtained from 42 patients who underwent
      posterior lumbar surgery were evaluated. All patients underwent CT and MRI before
      surgery. The pathologic grade was evaluated with a method based on hematoxylin
      eosin and toluidine blue staining. The radiographic grade was evaluated using the
      methods proposed by different authors. RESULTS: There was a moderate consistency
      between pathologic and radiographic grading for facet joint degeneration. The
      weighted kappa coefficients comparing pathologic with radiographic grading were
      0.506 for CT, 0.561 for MRI, and 0.592 for CT combined with MRI, respectively.
      Taking the pathologic examination as standard, the consistency of CT and MRI
      examination was also moderate, and the weighted kappa coefficient was 0.459.
      CONCLUSION: The radiographic examination has moderate accuracy and reliability
      for evaluating degeneration of facet joints. Therefore, a more accurate method
      for evaluating the degeneration of facet joints is necessary before performing
      spine non-fusion surgery that retains the facet joints.

PMID- 27025988
TI  - Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells.
AB  - Meiosis is a unique process that allows the generation of reproductive cells. It
      remains largely unknown how meiosis is initiated in germ cells and why non
      germline cells do not undergo meiosis. We previously demonstrated that knockdown
      of Max expression, a gene encoding a partner of MYC family proteins, strongly
      activates expression of germ cell-related genes in ESCs. Here we find that
      complete ablation of Max expression in ESCs results in profound cytological
      changes reminiscent of cells undergoing meiotic cell division. Furthermore, our
      analyses uncovers that Max expression is transiently attenuated in germ cells
      undergoing meiosis in vivo and its forced reduction induces meiosis-like
      cytological changes in cultured germline stem cells. Mechanistically, Max
      depletion alterations are, in part, due to impairment of the function of an
      atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data
      highlight MAX as a new regulator of meiotic onset. 

PMID- 27025989
TI  - Changes in Relative Thylakoid Protein Abundance Induced by Fluctuating Light in
      the Diatom Thalassiosira pseudonana.
AB  - One of the hallmarks of marine diatom biology is their ability to cope with rapid
      changes in light availability due to mixing of the water column and the lens
      effect. We investigated how irradiance fluctuations influence the relative
      abundance of key photosynthetic proteins in the centric diatom Thalassiosira
      pseudonana by means of mass-spectrometry-based approaches for relative protein
      quantitation. Most notably, fluctuating-light conditions lead to a substantial
      overall up-regulation of light-harvesting complex proteins as well as several
      subunits of photosystems II and I. Despite an initial delay in growth under FL,
      there were no indications of FL-induced photosynthesis limitation, in contrast to
      other photosynthetic organisms. Our findings further strengthen the notion that
      diatoms use a qualitatively different mechanism of photosynthetic regulation in
      which chloroplast-mitochondria interaction has overtaken crucial regulatory
      processes of photosynthetic light reactions that are typical for the survival of
      land plants, green algae, and cyanobacteria.

PMID- 27025990
TI  - [Papillary thyroid carcinoma in a child with congenital dyshormonogenetic
      hypothyroidism. Case report].
AB  - INTRODUCTION: Papillary thyroid carcinoma (PTC) is a rare childhood disease. The
      development of PTC in dyshormonogenetic congenital hypothyroidism (CH) is
      infrequent, with very few case reports in literature. OBJECTIVE: To report a case
      of PTC in a boy with dyshormonogenetic CH without goitre and exposed to ionising
      radiation. To evaluate relationships between these factors and development of
      PTC. CASE REPORT: We present a boy with dyshormonogenetic CH since birth. Early
      hormonal substitution was initiated, with subsequent normal levels of thyrotropin
      and thyroid hormones. He has also congenital cardiomyopathy, exposed to
      interventional treatment with 10 heart catheterisations, and approximately 26
      chest X-rays at paediatric doses. A thyroid nodule was found in thyroid
      echography at the age of 6 years old. Fine needle aspiration biopsy confirmed
      high probability of thyroid carcinoma (Bethesda 5). The pre-surgical thorax and
      cerebral scan showed no evidence of metastasis. The patient underwent total
      thyroidectomy. Pathological examination revealed a 0.5cm papillary thyroid micro
      carcinoma in the right lobe, with no evidence of dissemination. CONCLUSION:
      Genetic mutations and radiation exposure may play an important role in the
      development of PTC. There may be common pathways between dyshormonogenetic CH and
      thyroid carcinoma that need further investigation.

PMID- 27025991
TI  - Episodic ataxia type 2 manifests as epileptiform electroencephalographic activity
      with no epileptic attacks in two family members.
AB  - Here, we report two cases of episodic ataxia type 2 (EA2) in a 63-year-old woman
      and her 36-year-old daughter. The mother experienced recurrent attacks of
      cerebellar dysfunction lasting 4 to 5 hours since the age of 41 years. On several
      occasions, she was admitted to the emergency room, where she was diagnosed with
      epilepsy or stroke. Based on these diagnoses, she was treated with antiepileptic
      or anticoagulant drugs, but both treatments were eventually discontinued. The
      frequency of the attacks increased after the patient reached the age of 62.
      Interictal neurological examination demonstrated signs of slight cerebellar
      ataxia, i.e. saccadic eye movements, gaze-directed nystagmus, and mild truncal
      ataxia. Brain magnetic resonance imaging (MRI) showed cerebellar vermis atrophy.
      Electroencephalography (EEG) revealed various spike and wave patterns: solitary
      spikes, spike-and-slow wave complexes, and slow wave bursts. Photoparoxysmal
      response (PPR) type 3 was also observed. Treatment with acetazolamide abolished
      the patient's attacks almost completely. The daughter started experiencing 5- to
      10-minute ataxic episodes at the age of 16 years. Based on her epileptiform EEG
      activities with PPR (type 2), antiepileptic drugs (valproate and zonisamide) were
      prescribed. Despite pharmacological treatment, the attacks recurred; however,
      their frequency gradually decreased with time, until they almost entirely
      disappeared when the patient was 33. Unfortunately, migraine-like headaches arose
      instead. Subtle truncal ataxia was observed during interictal periods. Sanger
      sequencing of the exons of the CACNA1A gene revealed a novel single base deletion
      (c.3575delA) in both patients. Despite the difference in age of onset and
      clinical course, both patients showed clearly epileptiform EEG activities without
      experiencing the concurrent epileptic episodes. Thus, EA2 is a disease that may
      be misdiagnosed as epilepsy or stroke in the field of emergency medicine.

PMID- 27025992
TI  - A case of central nervous system relapse in acute promyelocytic leukemia.
AB  - A 70-year-old woman who have achieved complete remission (CR) of acute
      promyelocytic leukemia (APL) with all-trans retinoic acid and chemotherapy
      presented with abnormal sensation in the right lateral thigh and the bilateral
      legs. In addition, neurological examination revealed weakness of the left
      shoulder abduction, the right hand, and the bilateral lower limbs. Atypical
      promyelocytes were detected in the cerebrospinal fluid, in spite of normal
      finding in the peripheral blood smear. Magnetic resonance imaging showed
      gadolinium-enhanced multiple intradural/extramedullary lesions in the whole
      spine. Nerve conduction studies of the right limbs revealed sensorimotor
      conduction abnormalities, conspicuously in the posterior tibial and sural nerves.
      As a result, she was diagnosed as having intrathecal relapse of APL, associated
      with multiple mononeuropathy. The neurological symptoms were completely
      disappeared by intrathecal chemotherapy and whole-spine radiotherapy, suggesting
      that the neuropathy was possibly caused by meningeal infiltration affecting
      multiple spinal nerve roots. Since extramedullary or intrathecal relapse is
      extremely rare in APL compared with other types of leukemia, precise neurological
      evaluations and suitable treatment should be performed immediately, when APL
      patients with CR manifest some neurological symptoms.

PMID- 27025993
TI  - Tracheostomy and invasive mechanical ventilation in amyotrophic lateral
      sclerosis: decision-making factors and survival analysis.
AB  - BACKGROUND: Invasive and/or non-invasive mechanical ventilation are most
      important options of respiratory management in amyotrophic lateral sclerosis.
      METHODS: We evaluated the frequency, clinical characteristics, decision-making
      factors about ventilation and survival analysis of 190 people with amyotrophic
      lateral sclerosis patients from 1990 until 2013. RESULTS: Thirty-one percentage
      of patients underwent tracheostomy invasive ventilation with the rate increasing
      more than the past 20 years. The ratio of tracheostomy invasive ventilation in
      patients >65 years old was significantly increased after 2000 (25%) as compared
      to before (10%). After 2010, the standard use of non-invasive ventilation showed
      a tendency to reduce the frequency of tracheostomy invasive ventilation.
      Mechanical ventilation prolonged median survival (75 months in tracheostomy
      invasive ventilation, 43 months in non-invasive ventilation vs natural course, 32
      months). The life-extending effects by tracheostomy invasive ventilation were
      longer in younger patients <=65 years old at the time of ventilation support than
      in older patients. Presence of partners and care at home were associated with
      better survival. Following factors related to the decision to perform
      tracheostomy invasive ventilation: patients <=65 years old: greater use of non
      invasive ventilation: presence of a spouse: faster tracheostomy: higher
      progression rate; and preserved motor functions. No patients who underwent
      tracheostomy invasive ventilation died from a decision to withdraw mechanical
      ventilation. CONCLUSION: The present study provides factors related to decision
      making process and survival after tracheostomy and help clinicians and family
      members to expand the knowledge about ventilation.

PMID- 27025994
TI  - A case of familial amyloid polyneuropathy (FAP ATTR Ile107Val) with proximal
      muscle weakness in the lower extremities.
AB  - Proximal dominant muscle weakness is rare in transthyretin (TTR)-related familial
      amyloid polyneuropathy (FAP). A 69-year-old Japanese man developed numbness and
      dysesthesia of the first, second and third digits of both hands since 2008. He
      presented to our hospital with one year history of progressive proximal muscle
      weakness in the lower extremities since 2013. Neurological examinations revealed
      predominant proximal muscle weakness and atrophy with areflexia in the lower
      extremities, decreased superficial sensation in the first, second and third
      fingers of both hands, and decreased superficial and deep sensation in the lower
      extremities. Nerve conduction studies revealed an axonal degeneration type of
      sensorimotor polyneuropathy and bilateral carpal tunnel syndrome. Electromyogram
      revealed acute and chronic neurogenic changes predominantly in proximal muscles.
      We performed biopsy of the left quadriceps muscle and observed neurogenic changes
      in the muscle tissue and an amyloid deposition in the adipose tissue. This
      amyloid deposition was not seen in endomysium, perimysium and blood vessels.
      Genetic analysis of the TTR gene revealed the patient was heterozygous for a
      single nucleotide substitution c.379 A>G, which resulted in the replacement of
      valine with isoleucine at position 107 of the mature protein. We diagnosed his
      condition as FAP with Amyloid Transthyretin (ATTR) Ile107Val.

PMID- 27025996
TI  - Knowledge and Utilization of Computers Among Health Professionals in a Developing
      Country: A Cross-Sectional Study.
AB  - BACKGROUND: Incorporation of information communication technology in health care
      has gained wide acceptance in the last two decades. Developing countries are also
      incorporating information communication technology into the health system
      including the implementation of electronic medical records in major hospitals and
      the use of mobile health in rural community-based health interventions. However,
      the literature on the level of knowledge and utilization of information
      communication technology by health professionals in those settings is scarce for
      proper implementation planning. OBJECTIVE: The objective of this study is to
      assess knowledge, computer utilization, and associated factors among health
      professionals in hospitals and health institutions in Ethiopia. METHODS: A
      quantitative cross-sectional study was conducted on 554 health professionals
      working in 7 hospitals, 19 primary health centers, and 10 private clinics in the
      Harari region of Ethiopia. Data were collected using a semi-structured, self
      administered, and pre-tested questionnaire. Descriptive and logistic regression
      techniques using SPSS version 16.0 (IBM Corporation) were applied to determine
      the level of knowledge and identify determinants of utilization of information
      communication technology. RESULTS: Out of 554 participants, 482 (87.0%) of them
      responded to the questionnaire. Among them, 90 (18.7%) demonstrated good
      knowledge of computers while 142 (29.5%) demonstrated good utilization habits.
      Health professionals who work in the primary health centers were found to have
      lower knowledge (3.4%) and utilization (18.4%). Age (adjusted odds ratio
      [AOR]=3.06, 95% CI 0.57-5.37), field of study (AOR=3.08, 95% CI 1.65-5.73), level
      of education (AOR=2.78, 95% CI 1.43-5.40), and previous computer training
      participation (AOR=3.65, 95% CI 1.62-8.21) were found to be significantly
      associated with computer utilization habits of health professionals. CONCLUSIONS:
      Computer knowledge and utilization habits of health professionals, especially
      those who work in primary health centers, were found to be low. Providing
      trainings and continuous follow-up are necessary measures to increase the
      likelihood of the success of implemented eHealth systems in those settings.

PMID- 27025997
TI  - Reply to letter to the Editor.

PMID- 27025995
TI  - Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during
      Visual Discrimination.
AB  - Visual discrimination requires sensory processing followed by a perceptual
      decision. Despite a growing understanding of visual areas in this behavior, it is
      unclear what role top-down signals from prefrontal cortex play, in particular as
      a function of perceptual difficulty. To address this gap, we investigated how
      neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode
      task variables in a two-alternative forced choice visual discrimination task with
      high- and low-contrast visual input. About two-thirds of all recorded neurons in
      dl-FC were modulated by at least one of the two task variables, task difficulty
      and target location. More neurons in dl-FC preferred the hard trials; no such
      preference bias was found for target location. In individual neurons, this
      preference for specific task types was limited to brief epochs. Finally,
      optogenetic stimulation confirmed the functional role of the activity in dl-FC
      before target touch; suppression of activity in pyramidal neurons with the ArchT
      silencing opsin resulted in a decrease in reaction time to touch the target but
      not to retrieve reward. In conclusion, dl-FC activity is differentially recruited
      for high perceptual difficulty in the freely-moving ferret and the resulting
      signal may provide top-down behavioral inhibition. 

PMID- 27025998
TI  - Hiperglycemic hyperosmolar state: An unsual way of first appearance of type 1
      diabetes in children.

PMID- 27026009
TI  - Leaching of Lopinavir Amorphous Solid Dispersions in Acidic Media.
AB  - PURPOSE: Amorphous solid dispersions (ASDs) formulated with acid-insoluble
      (enteric) polymers form suspensions in acidic media where the polymer is largely
      insoluble. However, a small amount of drug can dissolve and a supersaturated
      solution may be generated. The goal of this study was to gain insight into the
      leaching mechanisms of both drug and polymer from the suspended particles,
      studying the impact of solution additives such as surfactants. METHODS: ASDs were
      prepared by spray drying lopinavir (LPV) with an enteric polymer, either
      hydroxypropylmethylcellulose acetate succinate (HPMCAS) or
      hydroxypropylmethylcellulose phthalate (HPMCP). Four surfactants and a suspending
      agent were added to the liquid media to evaluate the effect of these excipients
      on leaching. pH 3 and pH 5 buffers were used to investigate the effect of pH.
      RESULTS: The extent of drug leaching from the amorphous formulation was
      proportional to the crystalline solubility of the drug in the same medium. All
      surfactants promoted solubilization of LPV with the exception of poloxamer and
      sodium dodecyl sulfate-HPMCP combinations. A small amount of polymer ionization
      significantly enhanced LPV leaching in solutions containing an ionic surfactant.
      CONCLUSIONS: The mechanism of enhanced leaching appeared to be solubilization,
      with the apparent supersaturation remaining the same for systems containing the
      same polymer.

PMID- 27026010
TI  - In Vivo and In Vitro Evidence for Brain Uptake of 4-Phenylbutyrate by the
      Monocarboxylate Transporter 1 (MCT1).
AB  - PURPOSE: 4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for
      several neurodegenerative diseases. These activities require 4-PBA transport into
      the brain across the blood-brain barrier (BBB). The objective of the present
      study was to characterize the brain transport mechanism of 4-PBA through the BBB.
      METHODS: The brain transport of 4-PBA across the BBB was investigated following
      intravenous (IV) injection and internal carotid artery perfusion (ICAP) in vivo.
      The mechanism of transport was examined using TR-BBB cells, an in vitro model of
      the BBB. RESULTS: The volume of distribution (VD) of 4-PBA by rat brain was about
      7-fold greater than that of sucrose, a BBB impermeable vascular space marker,
      suggesting the blood-to-brain transport of 4-PBA through the BBB in the
      physiological state. [(14)C]4-PBA uptake by TR-BBB cells showed time-, pH- and
      concentration-dependence with a K m of 13.4 mM at pH 7.4 and 3.22 mM at pH 6.0.
      The uptake was Na(+) independent, and was significantly inhibited by alpha-cyano
      4-hydroxycinnamate (a typical inhibitor for monocarboxylate transport),
      endogenous monocarboxylate compounds and monocarboxylic drugs. Lactate and
      valproate competitively inhibited [(14)C]4-PBA uptake with K i value of 13.5 mM
      and 7.47 mM, respectively. These results indicate the role of monocarboxylate
      transporters (MCTs) in 4-PBA transport into the brain at the BBB. TR-BBB cells
      expressed mRNA of rMCT1, 2, and 4, especially, rMCT1 showed high mRNA expression
      level. In addition, [(14)C]4-PBA uptake was inhibited by rMCT1 specific small
      interfering RNA. CONCLUSION: The transport mechanism of 4-PBA from blood to brain
      across the BBB likely involves MCT1.

PMID- 27026011
TI  - Is C-reactive protein elevation a common finding in colonic diverticular disease?

PMID- 27026012
TI  - Effects of indexes of consciousness (IoC1 and IoC2) monitoring on remifentanil
      dosage in modified radical mastectomy: a randomized trial.
AB  - BACKGROUND: This study investigated the effects of indexes of consciousness (IoC1
      and IoC2) monitoring on remifentanil dosage. METHODS: In this randomized, single
      blinded, prospective study, 120 patients undergoing unilateral modified radical
      mastectomy were randomly assigned to the treatment group (T group, n = 60) or
      control group (C group, n = 60). In the T group, patients received both IoC1
      (sedation) and IoC2 (analgesia) monitoring, and remifentanil dosages were
      adjusted by anesthetists according to IoC2. In the C group, remifentanil dosages
      were adjusted based on the anesthetists' judgment according to the patients'
      vital signs. Remifentanil dose, adjustment frequency, infusion duration,
      intraoperative adverse events, and quality of anesthetic recovery were compared
      between the two groups. The primary outcome was the dose of remifentanil.
      RESULTS: Compared with the C group, mean remifentanil dosage was significantly
      higher in the T group (3.8 +/- 1.9 versus 3.2 +/- 1.2 MUg kg(-1) h(-1), P < 0.05)
      during the anesthetic period, as was the adjustment frequency of target
      controlled infusion (2.9 +/- 1.9 versus 2.0 +/- 1.2 times/surgery, P < 0.05), but
      there was no difference in infusion duration. Voluntary eye opening, extubation
      time, and recovery score were not significantly different between the two groups
      (P > 0.05). Total adverse events were significantly reduced in the T group (P <
      0.05). CONCLUSIONS: IoC1-targeted propofol dosing does not seem to be
      significantly different to hemodynamic-based monitoring, whereas IoC2 monitoring
      can increase remifentanil dosage during modified radical mastectomy, but the
      anesthetic process is more controllable and total adverse events are reduced,
      which improves the controllability of anesthesia. TRIAL REGISTRATION:  TRIAL
      REGISTRATION NUMBER: ChiCTR-TRC-13004101 , registered on 27 November 2013.

PMID- 27026014
TI  - Alkaptonuria: a disease with dark brown urine.

PMID- 27026013
TI  - Use of the bolus tracking technique for the tomographic evaluation of the uretero
      vesicular junction in dogs and assessment of dose records.
AB  - BACKGROUND: The aim of the work is the application of a bolus tracking technique
      for tomographic evaluation of the uretero-vesicular junction in dogs. Ten adult
      dogs (8-14 years) with variable body weight (2,8-32 kg) were enrolled in the
      prospective study. The patients were placed in sternal recumbency with a 10
      degrees  elevated pelvis and the visualization of the uretero-vesicular junction
      was obtained with the bolus tracking technique after intravenous administration
      of non-ionic contrast medium. In the post-contrast late phase a region of
      interest was placed within the lumen of the distal ureters and the density values
      were monitored before starting the helical scan. RESULTS: The uretero-vesicular
      junction was clearly visible in 100% of patients with the visualization of the
      endoluminal ureteral contrast enhancement and bladder washout. At the end of the
      tomographic study an evaluation of the dose records was performed and compared to
      human exposures reported in literature for the pelvic region. The effective dose
      estimated for each patient (37,5-138 mSv) proved to be elevated, when compared to
      those reported in human patients. CONCLUSION: The bolus tracking technique could
      be applied for the visualization of the uretero-vesicular junction in non
      pathological patients, placing the region of interest in the distal ureters. The
      high effective doses recorded in our study support the need of specific
      thresholds for veterinary patients, pointing out the attention for paediatric
      patient's exposure also in veterinary imaging.

PMID- 27026015
TI  - Role of the monocarboxylate transporter MCT1 in the uptake of lactate during
      active recovery.
AB  - PURPOSE: We assessed the role of monocarboxylate transporter 1 (MCT1) on lactate
      clearance during an active recovery after high-intensity exercise, by comparing
      genetic groups based on the T1470A (rs1049434) MCT1 polymorphism, whose influence
      on lactate transport has been proven. METHODS: Sixteen young male elite field
      hockey players participated in this study. All of them completed two 400 m
      maximal run tests performed on different days, followed by 40 min of active or
      passive recovery. Lactate samples were measured immediately after the tests, and
      at min 10, 20, 30 and 40 of the recoveries. Blood lactate decreases were
      calculated for each 10-min period. Participants were distributed into three
      groups according to the T1470A polymorphism (TT, TA and AA). RESULTS: TT group
      had a lower blood lactate decrease than AA group during the 10-20 min period of
      the active recovery (p = 0.018). This period had the highest blood lactate for
      the whole sample, significantly differing from the other periods (p <= 0.003).
      During the passive recovery, lactate declines were constant except for the 0-10
      min period (p <= 0.003), suggesting that liver uptake is similar in all the
      genetic groups, and that the difference seen during the active recovery is mainly
      due to muscle lactate uptake. CONCLUSIONS: These differences according to the
      polymorphic variant T1470A suggest that MCT1 affects the plasma lactate decrease
      during a crucial period of active recovery, where the maximal lactate amount is
      cleared (i.e. 10-20 min period).

PMID- 27026016
TI  - Microbiologic profile of infections in presumed aseptic revision spine surgery.
AB  - PURPOSE: Intra-operative cultures may be obtained in revision spine surgery
      despite the absence of pre-operative clinical markers of infection. The
      microbiologic profile of culture positive cases in which there is no clear
      evidence of infection preoperatively has not been described. The aim of this
      investigation is to report on the microbiologic profile of unexpected culture
      positive revision spine surgery cases. METHODS: We retrospectively reviewed 595
      consecutive revision spine surgeries performed between 2008 and 2013. Five
      hundred and seventy-eight revision surgeries were performed for diagnoses other
      than infection and were included in the study. RESULTS: Operative cultures were
      obtained in 112 cases (19.4 %). Cultures were positive in 45 cases.
      Pseudarthrosis was not only the most common diagnosis overall (49.1 %) in which
      intra-operative cultures were obtained, it was also the most common revision
      surgical diagnosis where cultures were positive (55.6 %). Propionibacterium acnes
      was cultured in 54.2 % of cases with the primary diagnosis of pseudarthrosis, but
      only in 40.9 % of cases with other diagnoses (P = 0.554). Overall, staphylococcal
      species were found most commonly (57.8 % of cases), but P. acnes was at least one
      of the isolates in 48.9 % of cases and was three times more common than any other
      organism. CONCLUSIONS: Nearly one in five patients with the diagnosis of
      pseudarthrosis were culture positive. More specifically, pseudarthrosis was the
      most common culture positive diagnosis and P. acnes species predominated in this
      patient population. Propionibacterium acnes was overwhelmingly the most common
      single organism cultured in revision spine surgery. Given this, we recommend all
      cultures be held for P. acnes, particularly in the setting of pseudarthrosis.

PMID- 27026018
TI  - Vitamin D deficiency: knowledge and practices among the adult population in
      Sharjah, United Arab Emirates.
AB  - Research demonstrate that vitamin D deficiency is significantly associated with
      bone diseases (e.g., osteoporosis), muscle cramps, back pain, heart diseases,
      diabetes mellitus, etc. The lack of knowledge and poor practice of study subjects
      regarding vitamin D deficiency became evident in this study. PURPOSE: Vitamin D
      is vital for the growth and development of the body throughout the life span. The
      aim of this study is to investigate the knowledge and the practices related to
      vitamin D deficiency among the adult population in Sharjah, UAE. METHODS: A cross
      sectional study was conducted among adults aged 20-40 years in Sharjah, UAE.
      Participants were selected from public places using convenience sampling method.
      They were subjected to a self-administered questionnaire. Data was analyzed using
      SPSS 20 software. All knowledge-related questions were summed up, where a correct
      answer was given 1 point and incorrect one a 0, yielding a score out of 43.
      Subjects' scores were then transformed to a percentage. RESULTS: A total of 503
      adults were included in the study. They had a mean age of 30 years (+/-5.47) with
      a relatively homogenous gender distribution (51 % females). The mean knowledge
      score on vitamin D deficiency was 16.7 out of 43 (39 %). Less than half of the
      respondents (43 %) knew that sunlight is the main source of vitamin D. The mean
      score for participants' practice was 2.34 out of 6 (39 %); 77 % of them reported
      that they tried to avoid sun exposure, and 97 % had not tested vitamin D levels
      in their blood before. CONCLUSION: The majority of the adults demonstrated
      significant lack of knowledge and poor practices towards vitamin D and its
      deficiency. Therefore, attempts to increase the awareness about this issue are
      required through establishing educational campaigns targeting the general public
      in Sharjah, UAE.

PMID- 27026017
TI  - Vitamin D status and bone mineral density in the Chinese population: a review.
AB  - Low vitamin D status is associated with low bone mass which, in turn, is an
      important predictor of fracture. However, data on this relationship in non
      Caucasian populations are scarce. This review shows such an association in the
      Chinese population in five of the 11 included studies. INTRODUCTION: In the
      elderly population, the serum 25-hydroxyvitamin D [25(OH)D] concentration is
      often inadequate. This may cause a lower bone mineral density (BMD), which is an
      important predictor of fracture. It is estimated that by 2050 more than half of
      all hip fractures worldwide will occur in Asia. However, data on the relationship
      between vitamin D status and BMD in a non-Caucasian population are scarce.
      Therefore, this study reviews the literature on the relationship between serum
      25(OH)D and BMD in the Chinese population. METHODS: A search was made in PubMed,
      EMBASE, Web of Science and Cochrane Library (up to December 2014) to identify
      relevant studies using the terms vitamin D status, bone mineral density, and
      Chinese. RESULTS: Of the 293 studies identified, 11 fulfilled the inclusion and
      exclusion criteria and were analyzed. Mean serum 25(OH)D concentrations ranged
      from 29-82 nmol/L. In 5 of the 11 studies, an association was found between
      vitamin D status and BMD in the Chinese population. CONCLUSION: The evidence for
      a relationship between the serum 25(OH)D concentration and BMD in the middle-aged
      and elderly Chinese population living in Asia appears to be limited and
      inconsistent.

PMID- 27026019
TI  - Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA
      Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients
      With Coronary Artery Disease: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
AB  - BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after
      implantation of newer-generation drug-eluting stents (DES) remains uncertain.
      Similarly, questions remain about the role of DAPT in long-term therapy of stable
      post-myocardial infarction (MI) patients. AIM: Our objective was to compare the
      incidence of death, major hemorrhage, MI, stent thrombosis, and major adverse
      cardiac events in patients randomized to prolonged or short-course DAPT after
      implantation of newer-generation DES and in secondary prevention after MI.
      METHODS: We used traditional frequentist statistical and Bayesian approaches to
      address the following questions: Q1) What is the minimum duration of DAPT
      required after DES implantation? Q2) What is the clinical benefit of prolonging
      DAPT up to 18 to 48 months? Q3) What is the clinical effect of DAPT in stable
      patients who are >1 year past an MI? RESULTS: We reviewed evidence from 11
      randomized controlled trials (RCTs) that enrolled 33 051 patients who received
      predominantly newer-generation DES to answer: A1) Use of DAPT for 12 months, as
      compared with use for 3 to 6 months, resulted in no significant differences in
      incidence of death (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.85 to
      1.63), major hemorrhage (OR: 1.65; 95% CI: 0.97 to 2.82), MI (OR: 0.87; 95% CI:
      0.65 to 1.18), or stent thrombosis (OR: 0.87; 95% CI: 0.49 to 1.55). Bayesian
      models confirmed the primary analysis. A2) Use of DAPT for 18 to 48 months,
      compared with use for 6 to 12 months, was associated with no difference in
      incidence of all-cause death (OR: 1.14; 95% CI: 0.92 to 1.42) but was associated
      with increased major hemorrhage (OR: 1.58; 95% CI: 1.20 to 2.09), decreased MI
      (OR: 0.67; 95% CI: 0.47 to 0.95), and decreased stent thrombosis (OR: 0.45; 95%
      CI: 0.24 to 0.74). A risk-benefit analysis found 3 fewer stent thromboses (95%
      CI: 2 to 5) and 6 fewer MIs (95% CI: 2 to 11) but 5 more major bleeds (95% CI: 3
      to 9) per 1000 patients treated with prolonged DAPT per year. Post hoc analyses
      provided weak evidence of increased mortality with prolonged DAPT. We reviewed
      evidence from 1 RCT of 21 162 patients and a post hoc analysis of 1 RCT of 15 603
      patients to answer: A3): Use of DAPT >1 year after MI reduced the composite risk
      of cardiovascular death, MI, or stroke (hazard ratio: 0.84; 95% CI: 0.74 to 0.95)
      but increased major bleeding (hazard ratio: 2.32; 95% CI: 1.68 to 3.21). A meta
      analysis and a post hoc analysis of an RCT in patients with stable cardiovascular
      disease produced similar findings. CONCLUSIONS: The primary analysis provides
      moderately strong evidence that prolonged DAPT after implantation of newer
      generation DES entails a tradeoff between reductions in stent thrombosis and MI
      and increases in major hemorrhage. Secondary analyses provide weak evidence of
      increased mortality with prolonged DAPT after DES implantation. In patients whose
      coronary thrombotic risk was defined by a prior MI rather than by DES
      implantation, the primary analysis provides moderately strong evidence of reduced
      cardiovascular events at the expense of increased bleeding.

PMID- 27026020
TI  - 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in
      Patients With Coronary Artery Disease: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines:
      An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary
      Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery,
      2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of
      Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the
      Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the
      Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014
      ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of
      Patients Undergoing Noncardiac Surgery.

PMID- 27026021
TI  - Divergence in male cricket song and female preference functions in three
      allopatric sister species.
AB  - Multivariate female preference functions for male sexual signals have rarely been
      investigated, especially in a comparative context among sister species. Here we
      examined male signal and female preference co-variation in three closely related,
      but allopatric species of Gryllus crickets and quantified male song traits as
      well as female preferences. We show that males differ conspicuously in either one
      of two relatively static song traits, carrier frequency or pulse rate; female
      preference functions for these traits also differed, and would in combination
      enhance species discrimination. In contrast, the relatively dynamic song traits,
      chirp rate and chirp duty cycle, show minimal divergence among species and
      relatively greater conservation of female preference functions. Notably, among
      species we demonstrate similar mechanistic rules for the integration of pulse and
      chirp time scales, despite divergence in pulse rate preferences. As these are
      allopatric taxa, selection for species recognition per se is unlikely. More
      likely sexual selection combined with conserved properties of preference filters
      enabled divergent coevolution of male song and female preferences.

PMID- 27026022
TI  - Alignment-independent technique for 3D QSAR analysis.
AB  - Molecular biochemistry is controlled by 3D phenomena but structure-activity
      models based on 3D descriptors are infrequently used for large data sets because
      of the computational overhead for determining molecular conformations. A diverse
      dataset of 146 androgen receptor binders was used to investigate how different
      methods for defining molecular conformations affect the performance of 3D
      quantitative spectral data activity relationship models. Molecular conformations
      tested: (1) global minimum of molecules' potential energy surface; (2) alignment
      to-templates using equal electronic and steric force field contributions; (3)
      alignment using contributions "Best-for-Each" template; (4) non-energy optimized,
      non-aligned (2D > 3D). Aggregate predictions from models were compared. Highest
      average coefficients of determination ranged from R Test (2) = 0.56 to 0.61. The
      best model using 2D > 3D (imported directly from ChemSpider) produced R Test (2)
      = 0.61. It was superior to energy-minimized and conformation-aligned models and
      was achieved in only 3-7 % of the time required using the other conformation
      strategies. Predictions averaged from models built on different conformations
      achieved a consensus R Test (2) = 0.65. The best 2D > 3D model was analyzed for
      underlying structure-activity relationships. For the compound strongest binding
      to the androgen receptor, 10 substructural features contributing to binding were
      flagged. Utility of 2D > 3D was compared for two other activity endpoints, each
      modeling a medium sized data set. Results suggested that large scale, accurate
      predictions using 2D > 3D SDAR descriptors may be produced for interactions
      involving endocrine system nuclear receptors and other data sets in which
      strongest activities are produced by fairly inflexible substrates.

PMID- 27026023
TI  - Prenatal presentation of pyruvate dehydrogenase complex deficiency.
AB  - We present the case of a female infant referred for prenatal MR evaluation of
      ventriculomegaly, which had been attributed by the referring obstetrician to
      aqueductal stenosis. Fetal MR confirmed ventriculomegaly but also demonstrated
      cerebral volume loss and white matter abnormalities. After birth, the infant
      developed persistent lactic acidosis. A diagnosis of pyruvate dehydrogenase
      complex deficiency was made on the basis of metabolic and molecular genetic
      studies. Ventriculomegaly is a common referral reason for fetal MR, yet there are
      few published reports of the radiographic findings that accompany inborn errors
      of metabolism, one potentially under-recognized cause of enlarged ventricles.
      This case contributes to this small body of literature on the imaging features of
      pyruvate dehydrogenase complex deficiency by describing pre- and postnatal MR
      findings and key clinical details. Our report emphasizes the necessity of
      considering pyruvate dehydrogenase complex deficiency and other metabolic
      disorders as potential etiologies for fetal ventriculomegaly since prompt
      diagnosis may allow for early initiation of treatment and improve outcome. 

PMID- 27026024
TI  - Automated radiogrammetry is a feasible method for measuring bone quality and bone
      maturation in severely disabled children.
AB  - BACKGROUND: Children with severe neurological impairment and intellectual
      disability are prone to low bone quality and fractures. OBJECTIVE: We studied the
      feasibility of automated radiogrammetry in assessing bone quality in this
      specific group of children. We measured outcome of bone quality and, because
      these children tend to have altered skeletal maturation, we also studied bone
      age. MATERIALS AND METHODS: We used hand radiographs obtained in 95 children
      (mean age 11.4 years) presenting at outpatient paediatric clinics. We used
      BoneXpert software to determine bone quality, expressed as paediatric bone index
      and bone age. RESULTS: Regarding feasibility, we successfully obtained a
      paediatric bone index in 60 children (63.2%). The results on bone quality showed
      a mean paediatric bone index standard deviation score of -1.85, significantly
      lower than that of healthy peers (P < 0.0001). Almost 50% of the children had
      severely diminished bone quality. In 64% of the children bone age diverged more
      than 1 year from chronological age. This mostly concerned delayed bone
      maturation. CONCLUSION: Automated radiogrammetry is feasible for evaluating bone
      quality in children who have disabilities but not severe contractures. Bone
      quality in these children is severely diminished. Because bone maturation
      frequently deviated from chronological age, we recommend comparison to bone-age
      related reference values.

PMID- 27026025
TI  - A quality improvement project to reduce hypothermia in infants undergoing MRI
      scanning.
AB  - BACKGROUND: Hypothermia prevention strategies during MRI scanning under general
      anesthesia in infants may pose a challenge due to the MRI scanner's technical
      constraints. Previous studies have demonstrated conflicting results related to
      increase or decrease in post-scan temperatures in children. We noted occurrences
      of post-scan hypothermia in anesthetized infants despite the use of routine
      passive warming techniques. OBJECTIVE: The aims of our quality improvement
      project were (a) to identify variables associated with post-scan hypothermia in
      infants and (b) to develop and implement processes to reduce occurrence of
      hypothermia in neonatal intensive care unit (NICU) infants undergoing MRI.
      MATERIALS AND METHODS: One hundred sixty-four infants undergoing MRI scanning
      were prospectively audited for post-scan body temperatures. A multidisciplinary
      team identified potential variables associated with post-scan hypothermia and
      designed preventative strategies: protocol development, risk factor
      identification, vigilance and use of a vacuum immobilizer. Another audit was
      performed, specifically focusing on NICU infants. RESULTS: In the initial phase,
      we found that younger age (P = 0.002), lower weight (P = 0.005), lower pre-scan
      temperature (P < 0.01), primary anesthetic technique with propofol (P < 0.01),
      advanced airway devices (P = 0.02) and being in the NICU (P < 0.01) were
      associated with higher odds for developing post-scan decrease in body
      temperature. Quality improvement processes decreased the occurrence of
      hypothermia in NICU infants undergoing MRI scanning from 65% to 18% (95%
      confidence interval for the difference, 26-70%, P < 0.001). CONCLUSION: Several
      variables, including being in the NICU, are associated with a decrease in post
      scan temperature in infants undergoing MRI scanning under sedation/general
      anesthesia. Implementation of strategies to prevent hypothermia in infants may be
      challenging in the high-risk MRI environment. We were able to minimize this
      problem in clinical practice by applying quality improvement principles.

PMID- 27026026
TI  - Drilling through lateral transmuscular portal lowers the risk of suprascapular
      nerve injury during arthroscopic SLAP repair.
AB  - PURPOSE: The aim of our study was to evaluate the risk of medial glenoid
      perforation and possible injury to suprascapular nerve during arthroscopic SLAP
      repair using lateral transmuscular portal. METHODS: Ten cadaveric shoulder
      girdles were isolated and drilled at superior glenoid rim from both anterior
      superior portal (1 o'clock) and lateral transmuscular portal (12 o'clock) for
      SLAP repairs. Drill hole depth was determined by the manufacturer's drill stop
      (20 mm), and any subsequent drill perforations through the medial bony surface of
      the glenoid were directly confirmed by dissection. The bone tunnel depth and
      subsequent distance to the suprascapular nerve, scapular height and width, were
      compared for investigated locations. RESULTS: Four perforations out of ten (40 %)
      occurred through anterior-superior portal with one associated nerve injury. One
      perforation out of ten (10 %) occurred through lateral transmuscular portal
      without any nerve injury. The mean depth was calculated as 17.6 mm (SD 3) for
      anterior-superior portal and 26.5 mm (SD 3.6) for lateral transmuscular portal (P
      < 0.001). CONCLUSIONS: It is anatomically possible that suprascapular nerve could
      sustain iatrogenic injury during labral anchor placement during SLAP repair.
      However, lateral transmuscular portal at 12 o'clock drill entry location has
      lower risk of suprascapular nerve injury compared with anterior-superior portal
      at 1 o'clock drill entry location.

PMID- 27026027
TI  - Recurrent posterior knee laxity: diagnosis, technical aspects and treatment
      algorithm.
AB  - PURPOSE: Aim of this study was to determine the characteristics, clinical and
      radiological diagnostic methods of PCL isolated and combined knee injuries.
      METHODS: One hundred and twelve patients with a recurrent posterior knee laxity
      were surgically treated. Clinical examination, MRI, TelosTM stress dynamic X
      rays, KT-1000 measurements and the IKDC questionnaire were used to diagnose and
      evaluate these injuries. RESULTS: Median follow-up was 4.5 years (2-11 years).
      Thirty-two patients (28.6 %) had an isolated posterior laxity, 53 (47.3 %) a
      posterior posterolateral laxity, 21 (18.7 %) a posterior posteromedial laxity and
      six (5.4 %) patients had a complex posterior and mediolateral laxity. Road
      traffic accidents and sports injuries were the main causes of trauma. The mean
      preoperative value of posterior tibial translation was 13.5 mm (SD 1.4) and the
      mean postoperative value was 4.4 mm (SD 1.7) as measured with the Telos device.
      In the cases with a concomitant ACL rupture, the mean preoperative value of
      anterior tibial translation was 6.5 mm (SD 1.3) and the mean postoperative value
      was 1.7 mm (SD 0.8). The mean pre- and postoperative IKDC scores were 74.5 (SD
      4.2) and 87.9 (SD 3.1), respectively. Meniscal and/or cartilage injuries were
      found in 80 patients (71.4 %). CONCLUSIONS: Recurrent posterior knee laxity can
      be restored with the one-stage PCL reconstruction using a quadriceps graft and
      reconstruction of the posteromedial-posterolateral lesions using the LaPrade
      techniques. The benefits of this study include enabling surgeons to accurately
      manage these injuries from a clinical perspective, and treating them with a
      specific surgical algorithm. LEVEL OF EVIDENCE: III.

PMID- 27026028
TI  - A new quantitative measure for radiologic osteoarthritis of the lateral knee
      compartment distinguishes patients with longstanding lateral meniscectomy from
      non-pathological knees.
AB  - PURPOSE: Common radiologic scores to evaluate knee osteoarthritis (OA) have been
      widely used but are descriptive and may lack objectivity. The aim of this study
      was to develop a quantitative and objective radiologic measure for the evaluation
      of lateral knee compartment OA. Furthermore, we tested the reliability of this
      new measure and its correlation to well-accepted radiologic scores. METHODS: This
      retrospective study was performed within the context of a multi-centre long-term
      follow-up (15-25 years) of a patient cohort after partial or total lateral
      meniscectomy (n = 36 knees). In addition, 99 radiographs of clinically and
      radiologically normal knees were obtained from a control group. Anteroposterior
      weight-bearing views (0 degrees ) and Schuss (45 degrees ) views were analysed.
      The joint height of the lateral knee compartment was measured on the lateral
      border (lateral joint space height) and in the centre (central joint space
      height, CJSH) and normalized with respect to the width of the lateral compartment
      (X). All measurements were taken independently by two observers, allowing for
      inter- and intra-observer reliability assessments. The results of the two groups
      were compared using an analysis of covariance. Finally, the correlations between
      the results and the Fairbank and Kellgren & Lawrence scores were determined using
      a Spearman rho rank order correlation. RESULTS: The normalized joint space height
      in the centre of the compartment on the Schuss view (CJSH/X) showed the highest
      intra- (ICC = 0.980) and inter-observer reliability (ICC = 0.982). There was a
      significant difference in CJSH/X between the control (0.19 +/- 0.05) and the
      meniscectomized knees (0.08 +/- 0.07) (p < 0.001). CJSH/X showed a significant
      decline of 11 % per 10 years in the meniscectomy group. A negative correlation
      could be found between CJSH/X and the Fairbank (rho = -0.751; p < 0.001) and
      Kellgren & Lawrence scores (rho = -0.712; p < 0.001). A cut-off value of 0.14 of
      CJSH/X was defined-representing one standard deviation below the mean of the
      control group-from which measurements were considered as pathologic. CONCLUSION:
      The normalized joint space height measured in the centre of the lateral knee
      compartment from a Schuss view, CJSH/X, was highly reproducible and showed a
      significant correlation to established radiologic scores. This new measure has
      the advantage of being objective and dimensionless and thus independent of the
      size of the radiograph. The normative values provided by our healthy control
      knees are useful to help establish an early diagnosis of radiologic lateral knee
      compartment OA. LEVEL OF EVIDENCE: Retrospective diagnostic study, Level III.

PMID- 27026029
TI  - An in vitro analysis of medial structures and a medial soft tissue reconstruction
      in a constrained condylar total knee arthroplasty.
AB  - PURPOSE: The aim of this study was to quantify the medial soft tissue
      contributions to stability following constrained condylar (CC) total knee
      arthroplasty (TKA) and determine whether a medial reconstruction could restore
      stability to a soft tissue-deficient, CC-TKA knee. METHODS: Eight cadaveric knees
      were mounted in a robotic system and tested at 0 degrees , 30 degrees , 60
      degrees , and 90 degrees  of flexion with +/-50 N anterior-posterior force, +/-8
      Nm varus-valgus, and +/-5 Nm internal-external torque. The deep and superficial
      medial collateral ligaments (dMCL, sMCL) and posteromedial capsule (PMC) were
      transected and their relative contributions to stabilising the applied loads were
      quantified. After complete medial soft tissue transection, a reconstruction using
      a semitendinosus tendon graft was performed, and the effect on kinematic
      behaviour under equivocal conditions was measured. RESULTS: In the CC-TKA knee,
      the sMCL was the major medial restraint in anterior drawer, internal-external,
      and valgus rotation. No significant differences were found between the rotational
      laxities of the reconstructed knee to the pre-deficient state for the arc of
      motion examined. The relative contribution of the reconstruction was higher in
      valgus rotation at 60 degrees  than the sMCL; otherwise, the contribution of the
      reconstruction was similar to that of the sMCL. CONCLUSION: There is contention
      whether a CC-TKA can function with medial deficiency or more constraint is
      required. This work has shown that a CC-TKA may not provide enough stability with
      an absent sMCL. However, in such cases, combining the CC-TKA with a medial soft
      tissue reconstruction may be considered as an alternative to a hinged implant.

PMID- 27026030
TI  - The biomechanical effects of graft rotation on ACL reconstruction tunnel
      mismatch.
AB  - PURPOSE: Bone block protrusion out of the tibial tunnel due to a relatively long
      graft is a common complication in anterior cruciate ligament surgical
      reconstruction with a patellar tendon. One possible solution is to shorten the
      patellar tendon graft already fixed in the femur by applying external rotation.
      This study aimed to evaluate the degree of shortening and biomechanical changes
      in porcine patellar grafts subjected to relatively higher degrees of rotation.
      Data obtained with rotations of 0 degrees , 540 degrees , 720 degrees , and 900
      degrees  were compared. METHODS: Forty patellar porcine ligaments were subjected
      to biomechanical tests of degree of shortening, modulus of elasticity and maximum
      tension in the tendon before rupture. Tests were conducted using a universal
      mechanical testing machine and a computerized system for acquiring strength and
      deformation data. RESULTS: Progressive shortening of the patellar ligament
      occurred with rotations of 0 degrees , 540 degrees  and 720 degrees . However,
      the degree of shortening showed no statistically significant difference as
      rotation increased from 720 degrees  to 900 degrees . Decreased modulus of
      elasticity was observed compared with the graft rotation at 0 degrees  in all
      groups tested, but no statistically significant differences were observed among
      540 degrees , 720 degrees  and 900 degrees . The maximum tension of the patellar
      tendon showed no change before rupture, regardless of the degree of rotation.
      CONCLUSIONS: Rotating the patellar tendon is an efficient method for shortening a
      relatively long graft; however, more biomechanical studies are necessary to
      recommend this technique in clinical practice owing to the resulting decrease in
      graft stiffness that could compromise knee stability.

PMID- 27026031
TI  - The role of wound closure in total knee arthroplasty: a systematic review on knee
      position.
AB  - PURPOSE: Post-operative range of motion (ROM) is one of the most important
      parameters to assess, following total knee arthroplasty (TKA). The aims of the
      present systematic review were to analyse the available literature and determine
      if closing the knee in flexion or extension influences post-operative ROM,
      clinical outcomes, and complications following TKA. METHODS: A systematic review
      was performed using the keywords "total knee arthroplasty", "total knee
      replacement", and "wound closure" or "joint closure" or "extension" or "flexion"
      with no limit regarding the year of publication. The review was limited to the
      English-language articles, and each article was evaluated with a modified Coleman
      Methodology Score (mCMS). RESULTS: Six articles met inclusion criteria. The
      initial cohort included 202 TKAs in the flexion group and 201 in the extension
      group. Three hundred and ninety-seven TKAs were evaluated with an average follow
      up of 8 months. There was no statistical difference (n.s.) between the two groups
      in terms of the average post-operative flexion. There were no statistical
      differences between the two groups regarding post-operative functional scores and
      VAS scores (n.s.). The average mCMS was 70.9, indicating good methodological
      quality in the included studies. CONCLUSIONS: The findings of the present review
      did not show any statistically significant differences in terms of post-operative
      flexion ROM, functional scores, or complications related to the position of the
      knee at the time of joint and wound closure during TKA. There is no clear
      advantage to either closure method based on the currently available evidence, and
      therefore, this choice should be based on surgeon preference.

PMID- 27026032
TI  - Incidence of pulmonary emboli on chest computed tomography angiography based upon
      referral patterns.
AB  - Pulmonary embolism (PE) is a potentially lethal condition, and the diagnosis of
      PE can be difficult. The purpose of this study is to evaluate the incidence of PE
      on chest computed tomography angiography (CTA) studies ordered in the inpatient,
      outpatient, and emergency department (ED) settings and further segregated based
      on the adult and pediatric populations, and by the ordering clinician (attending
      physicians, resident physicians, or physician extenders). A retrospective review
      of chest CTA examinations performed between July 1,2009 and June 30, 2010 was
      performed. Of 5848 adult CTA studies, PE was diagnosed in 594 (10.1 %). Of these
      positive studies, 315 (53 %) were inpatient, 234 (39.4 %) were ED patients, and
      45 (7.6 %) were outpatient. Four hundred sixty-four of 4445 (10.4 %) CTA
      examinations ordered by attending physicians were positive for PE. Seventy-four
      of the 801 (9.2 %) CTA examinations ordered by resident physicians were positive
      for PE. Fifty-six of the 608 CTA examinations ordered by physician extenders were
      positive for PE. Thirty-three pediatric CTA studies for PE met criteria and none
      of them indicated PE. There is no significant difference in the incidence of PE
      in chest CTA based on setting or ordering clinician. 

PMID- 27026033
TI  - Epithelioid Hemangioendothelioma: a Rare Primary Thyroid Tumor with Confirmation
      of WWTR1 and CAMTA1 Rearrangements.
AB  - We report a rare case of epithelioid hemangioendothelioma as a primary thyroid
      tumor. To our knowledge, there are only two prior unequivocal cases of primary
      thyroid epithelioid hemangioendothelioma reported in the English literature. This
      is the first case in the thyroid with molecular confirmation. 

PMID- 27026034
TI  - PIM-1 mixed matrix membranes for gas separations using cost-effective
      hypercrosslinked nanoparticle fillers.
AB  - High-free-volume glassy polymers, such as polymers of intrinsic microporosity
      (PIMs) and poly(trimethylsilylpropyne), have attracted attention as membrane
      materials due to their high permeability. However, loss of free volume over time,
      or aging, limits their applicability. Introduction of a secondary filler phase
      can reduce this aging but either cost or instability rules out scale up for many
      fillers. Here, we report a cheap, acid-tolerant, nanoparticulate hypercrosslinked
      polymer 'sponge' as an alternative filler. On adding the filler, permeability is
      enhanced and aging is strongly retarded. This is accompanied by a CO2/N2
      selectivity that increases over time, surpassing the Robeson upper bound. 

PMID- 27026036
TI  - Posterior reversible encephalopathy syndrome in multiple system atrophy.

PMID- 27026035
TI  - Autonomic Testing in Women with Chronic Pelvic Pain.
AB  - PURPOSE: We determined whether abnormal autonomic nervous system innervation of
      the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome)
      differently than other chronic pelvic pain. MATERIALS AND METHODS: In this
      institutional review board approved protocol 39 healthy controls and 134 subjects
      were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42
      with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study.
      Autonomic nervous system evaluations included deep breathing, the Valsalva
      maneuver, and the tilt table and sudomotor tests. The latter evaluates autonomic
      neuropathy. A modified validated composite autonomic laboratory score was
      applied. RESULTS: Median age in the IC/BPS group was 47.5 years (range 21 to 78),
      greater than in healthy controls (34 years, range 20 to 75, p = 0.006), the
      myofascial pelvic pain group (33 years, range 22 to 56, p = 0.004) and the IC/BPS
      plus myofascial pelvic pain group (38 years, range 18 to 64, p = 0.03). Body mass
      index did not significantly differ but the myofascial pelvic pain and IC/BPS plus
      myofascial pelvic pain groups had a higher body mass index than healthy controls
      (p = 0.05 and 0.03, respectively). Cardiovascular and adrenergic indexes did not
      differ. The tilt table test showed more orthostatic intolerance in all chronic
      pelvic pain groups. Tilt table test diagnoses (orthostatic hypotension, postural
      tachycardia syndrome and reflex syncope) were rare. Baseline heart rate was
      higher in all chronic pelvic pain groups (p = 0.004). Compared to healthy
      controls all myofascial pelvic pain groups showed significantly more clear-cut
      autonomic neuropathy, defined as a sweat score of 3 or greater (vs IC/BPS plus
      myofascial pelvic pain p = 0.007 and vs myofascial pelvic pain p = 0.03).
      CONCLUSIONS: Some chronic pelvic pain types show autonomic neuropathy and some
      show vagal withdrawal. In all types orthostatic intolerance likely reflects
      central sensitization and perhaps catastrophizing. Some of these findings suggest
      novel therapeutic targets.

PMID- 27026037
TI  - Thioredoxin domain-containing protein 12 from Oplegnathus fasciatus: Molecular
      characterization, expression against immune stimuli, and biological activities
      related to oxidative stress.
AB  - Thioredoxin domain-containing protein 12 (TXNDC12) is a small, disulfide
      containing protein that belongs to the thioredoxin (TXN) superfamily. In the
      present study, we identified and characterized a TXNDC12-like gene, designated
      OfTXNDC12, from rock bream, Oplegnathus fasciatus. OfTXNDC12 consists of seven
      exons interrupted by six introns. Comparative genomic structural analysis
      revealed that the TXNDC12 of vertebrates is a structurally conserved gene. The
      coding sequence of OfTXNDC12 comprises 522 bp, which encodes 173 amino acid
      residues with the conserved thioredoxin active site motif, CGAC, and a probable C
      terminal ER retrieval motif, GDEL. Transcriptional analysis of OfTXNDC12 showed
      the highest concentrations of the mRNA transcript in the liver, implying that it
      has a significant role in the liver under normal physiological conditions. In
      comparison, injection of lipopolysaccharide, Edwardsiella tarda, Streptococcus
      iniae, polyinosinic:polycytidylic acid (poly[I:C]) and rock bream iridovirus
      mostly triggered greater upregulation of OfTXNDC12 transcript levels in liver
      than in gill tissue, supporting its potential functional importance in the liver.
      Insulin disulfide reduction assay showed that the recombinant fusion protein
      (rOfTXNDC12) possesses significant thioredoxin activity. Treatment of LNCaP cells
      with the recombinant protein along with H2O2 revealed that rOfTXNDC12 increased
      the viability of cells and further supported its putative antioxidant capacity.
      Taken together, the results from our study suggest that OfTXNDC12 encodes for a
      potent antioxidant involved in redox regulation that shows significant responses
      to immune stimuli. 

PMID- 27026038
TI  - Regulation of Rubisco gene expression in C4 plants.
AB  - Ribulose-1,5-bisphosphate-carboxylase/oxygenase (Rubisco) incorporates inorganic
      carbon into an organic form, making this chloroplastic enzyme one of the most
      essential factors for all life on earth. Despite its central role in
      photosynthesis, research into regulation of the chloroplast rbcL and nuclear RbcS
      genes that encode this enzyme has lagged behind other plant gene systems. A major
      characteristic of kranz-type C4 plants is the accumulation of Rubisco only within
      chloroplasts of internalized bundle sheath cells that surround the leaf vascular
      centers. In plants that utilize the less common single cell C4 system, Rubisco
      accumulates only within one type of dimorphic chloroplasts localized to a
      specific region of leaf chlorenchyma cells. Understanding regulatory processes
      that restrict Rubisco gene expression to only one cell type or chloroplast type
      is a major focus of C4 research. Regulatory steps may include transcriptional,
      post-transcriptional, and post-translational processes.

PMID- 27026039
TI  - Monitoring of partial and full venous outflow obstruction in a porcine flap model
      using laser speckle contrast imaging.
AB  - BACKGROUND: In microsurgery, there is a demand for more reliable methods of post
      operative monitoring of free flaps, especially with regard to tissue-threatening
      obstructions of the feeding arteries and draining veins. In this study, we
      evaluated laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF)
      to assess their possibilities to detect partial and full venous outflow
      obstruction, as well as full arterial occlusion, in a porcine flap model.
      METHODS: Cranial gluteal artery perforator flaps (CGAPs) were raised, and
      arterial and venous blood flow to and from the flaps was monitored using
      ultrasonic flow probes. The venous flow was altered with an inflatable cuff to
      simulate partial and full (50% and 100%) venous obstruction, and arterial flow
      was completely obstructed using clamps. The flap microcirculation was monitored
      using LSCI and LDF. RESULTS: Both LDF and the LSCI detected significant changes
      in flap perfusion. After partial (50%) venous occlusion, perfusion decreased from
      baseline, LSCI: 63.5 +/- 12.9 PU (p = 0.01), LDF 31.3 +/- 15.7 (p = 0.64). After
      100% venous occlusion, a further decrease in perfusion was observed: LSCI 54.6 +/
      14.2 PU (p < 0.001) and LDF 16.7 +/- 12.8 PU (p < 0.001). After release of the
      venous cuff, LSCI detected a return of the perfusion to a level slightly, but not
      significantly, below the baseline level 70.1 +/- 11.5 PU (p = 0.39), while the
      LDF signal returned to a level not significant from the baseline 36.1 +/- 17.9 PU
      (p > 0.99). Perfusion during 100% arterial occlusion decreased significantly as
      measured with both methods, LSCI: 48.3 +/- 7.7 (PU, p < 0.001) and LDF: 8.5 +/-
      4.0 PU (p < 0.001). During 50% and 100% venous occlusion, LSCI showed a 20% and
      26% intersubject variability (CV%), respectively, compared to 50% and 77% for
      LDF. CONCLUSIONS: LSCI offers sensitive and reproducible measurements of flap
      microcirculation and seems more reliable in detecting decreases in blood
      perfusion caused by venous obstruction. It also allows for perfusion measurements
      in a relatively large area of flap tissue. This may be useful in identifying
      areas of the flap with compromised microcirculation during and after surgery.

PMID- 27026040
TI  - The contralateral breast flap in autologous breast reconstruction.

PMID- 27026041
TI  - Hemozoin Enhances Maturation of Murine Bone Marrow Derived Macrophages and
      Myeloid Dendritic Cells.
AB  - BACKGROUND: Falciparum malaria is a severe health burden worldwide. Antigen
      presenting cells are reported to be affected by erythrocytic stage of the
      parasite. Malarial hemozoin (HZ), a metabolite of malaria parasite, has adjuvant
      properties and may play a role in the induction of immune response against the
      parasite. OBJECTIVE: To determine the immunological impact of hemozoin on the
      capacity of innate immune cells maturation. METHODS: Plasmodium falciparum (F32
      strain) was cultured in O+ blood group up to 18% parasitemia. Natural hemozoin
      was extracted from infected red blood cells. Murine bone marrow derived
      macrophages and myeloid dendritic cells were stimulated with 4 MUg/mL or 40
      MUg/mL of synthetic hemozoin (beta-hematin) or natural hemozoin. We assessed the
      immunomodulatory role of synthetic or natural hemozoinin vitro by flowcytometric
      analysis. RESULTS: The maturation markers MHC-II, CD80 and CD86 were
      significantly upregulated (p<0.05) on the surface of murine bone marrow derived
      macrophages or myeloid dendritic cells. Data confirmed the potential of
      macrophages or myeloid dendritic cells, through hemozoin activation, to establish
      an innate immune response against malaria parasites. CONCLUSION: Both synthetic
      and natural hemozoin are potent inducers of cellular immunity against malaria
      infection. However, natural hemozoin is a stronger inducer as compared to
      synthetic hemozoin.

PMID- 27026042
TI  - T-helper Type 1 and 2 Cytokine Levels in Patients with Benign and Malignant
      Salivary Gland Tumors.
AB  - BACKGROUND: Salivary gland tumors are among malignancies that have high
      recurrence rate. Immune responses in salivary gland tumors have not been well
      elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a
      role in the outcome of head and neck cancers. OBJECTIVE: To evaluate the serum
      levels of interferon gamma (IFN-gamma), as the hallmark of Th1 cytokines, and
      interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign
      and malignant salivary gland tumors in comparison with healthy controls. METHODS:
      Fifty patients with benign and 14 patients with malignant salivary gland tumors,
      as well as 23 healthy individuals were recruited. Serum levels of IFN-gamma and
      IL-4 were measured using ELISA method. Nonparametric tests were used for data
      analysis. RESULTS: Serum levels of IFN-gamma and IL-4 were found not to be
      significantly different in patients compared to the control group (0.68+/-0.29
      vs. 1.03+/-0.57pg/ml, p=0.58 for IFN-gamma, 4.57+/-1.57vs. 4.41+/-1.31pg/ml,
      p=0.28 for IL-4). IFN-gamma and IL-4 serum levels were also not significantly
      different between patients with benign and malignant salivary gland tumors
      (p=0.54 and p=0.86, respectively). CONCLUSION: The systemic levels of IL-4 and
      IFN-gamma seem not to be associated with salivary gland tumor in our study.
      Investigation of other cytokines produced by Th1 and Th2 cells are warranted.

PMID- 27026043
TI  - Interferon beta-1a and Atorvastatin in the Treatment of Multiple Sclerosis.
AB  - BACKGROUND: Statins, widely used cholesterol-lowering agents, have also been
      demonstrated to have anti-inflammatory and immunomdulatory effects. OBJECTIVE: To
      evaluate the effects of atorvastatin in combination with Interferon-beta in the
      treatment of multiple sclerosis (MS) in a randomized controlled clinical trial.
      METHODS: Multiple sclerosis patients were randomized independently, in a double
      blind design, into one of two treatment groups. Control group (n=45) received 30
      MUg/week interferon beta-1a via intra-muscular injection. Atorvastatin-treated
      group (n=50) received interferon beta-1a similar to control group in addition to
      atorvastatin (40 mg/day) for 18-months. All clinical and immunological variables
      were measured at the baseline and at the end of the study. RESULTS: There was no
      significant difference between the two groups in the expanded disability status
      scale scores and the number of gadolinium-enhancing lesions during the 18-month
      treatment period. After 18 months, the levels of interleukin (IL)-4, IL-10,
      transforming growth factor-beta and serum ferric reducing antioxidant power in
      the atorvastatin treatment group were significantly higher than the control
      group. Levels of IL-17, TNF-alpha and lymphocyte proliferation in the
      atorvastatin treatment group were significantly lower than the control group.
      CONCLUSION: Although combined atorvastatin and interferon-beta do not change the
      clinical course of MS, atorvastatin might have beneficial effects in MS treatment
      possibly through inducing anti-inflammatory responses.

PMID- 27026044
TI  - Expression of Basophil Activation Markers in Pediatric Asthma.
AB  - BACKGROUND: Asthma is very common in children and its diagnosis is based on
      clinical manifestations, which can be misdiagnosed as other respiratory diseases
      with similar signs and symptoms. OBJECTIVE: To analyze the expression of ST2L and
      CD203c in the diagnosis of pediatric asthma. METHODS: Basophils were purified
      from whole blood samples of patients and healthy controls using Ficol-Paque
      gradient and Basophil Isolation Kit. RNA extraction was done by RNX-Plus solution
      and after synthesis of cDNA, the gene expression was analyzed by means of real
      time PCR. RESULTS: Patients expressed significantly higher levels of CD203c than
      healthy controls (p=0.01). Although there was an increase in the transcription
      level of ST2L gene in patients, the results were not statistically significant
      compared to those obtained from the healthy controls (p>0.05). A Specificity of
      60% and a sensitivity of 73% were found using ROC curve for CD203c expression.
      Patients with positive family history of asthma exhibited more CD203c and ST2L
      expression (p<0.05). CONCLUSION: It is proposed that determining CD203c
      expression by real time PCR may be an effective technique for diagnosis of
      pediatric asthma.

PMID- 27026045
TI  - Effect of Anger Patterns and Depression on Serum IgA and NK Cell Frequency.
AB  - BACKGROUND: There are conflicting findings about relationship between depression
      and anger with immunological parameters. OBJECTIVE: To investigate the
      relationship between anger patterns and immune system in depressed patients.
      METHODS: Thirty-five patients with major depressive disorder were selected
      according to DSM-IV criteria. The Hamilton Depression Scale and Spielberger Anger
      questionnaires were used to determine severity of depression and "anger
      expression pattern", respectively. The control group without a previous history
      of mental illness was also selected. In the group of patients with moderate
      depression, serum IgA levels and NK cell percentage were measured. RESULTS: Mean
      differences of all types of "anger expression pattern", including; "state-trait
      anger", "anger expression out", "anger expression in", "anger control out" and
      "anger control in", between study and control groups, were statistically
      significant (p<0.05). Difference in mean serum levels of IgA in either group was
      not significant (p=0.9), but the mean difference was significant in terms of NK
      cell percentage in both groups (p=0.04). There was no significant relationship
      between IgA levels and percentage of NK- cell with all types of "anger expression
      pattern" in both groups. Only in the control group, IgA had significant
      correlation with anger control out (p=0.04). CONCLUSION: Moderately depressed
      patients versus control group had higher Spielberger scores in all types of anger
      expression pattern except anger control-out and anger control-in. We found no
      evidence supporting the relationship between" anger expression pattern" and IgA
      levels and NK cell percentage; however, it seems that depression itself causes
      reduced number of NK cells and increased IgA levels.

PMID- 27026047
TI  - Stable Down-Regulation of HLA Class-I by Serum Starvation in Human PBMCs.
AB  - BACKGROUND: The human leukocyte antigen (HLA) matching between organ donor and
      recipient is an acceptable strategy in clinical transplantation since 1964.
      However, in bone marrow transplantation, finding matched donors is often
      problematic. Thus new method for down regulation of HLA can be an alternative
      strategy to solve this problem. OBJECTIVE: To examine the effect of serum
      starvation on HLA class I expression in human peripheral blood mononuclear cells
      (PBMCs). METHODS: PBMCs were cultured in RPMI-1640 supplemented with 10% FBS (non
      starved cells) as well as in medium only (starved cells) for 16, 24, 48, 72, 96h
      under standard cell culture conditions. The pattern of cell death and HLA class I
      expression was determined by flowcytometry. Antigenicity of the starved PBMCs was
      evaluated in a one-way mixed lymphocyte culture by MTT assay. RESULTS: Mean
      fluorescence intensity (MFI) of different indicated starved PBMCs gradually
      decreased and this reduction was stable after 96h of re-feeding with medium
      containing FBS. Under serum starvation condition, PBMCs showed apoptotic cell
      death pattern. There was a linear correlation between percentages of cells, which
      exhibited the late apoptosis death pattern and serum starvation period (r=0.88,
      p<0.01). Surprisingly, the starved PBMCs lost their stimulatory property in mixed
      culture with allo-reactive lymphocyte. CONCLUSIONS: Membrane HLA class I
      expression could be stably reduced in 96h starved human PBMCs culture condition,
      decreasing their allo-reactivity while their viability rate is enough for
      possible clinical application.

PMID- 27026046
TI  - MMP9 Promoter Polymorphism (-1562 C/T) Does not Affect the Serum Levels of
      Soluble MICB and MICA in Breast Cancer.
AB  - BACKGROUND: The role of Matrix Metalloproteinase 9 (MMP9) in tumor invasion and
      progression is prominent. A single nucleotide polymorphism (SNP) in the promoter
      region of MMP9 (-1562 C/T) increases the transcription and expression of this
      gene. On the other hand, MHC class I chain-related protein A and B (MICA/B) in
      soluble forms may impair tumor immunogenicity by reducing Natural Killer Group 2D
      (NKG2D) densities on NK cells and MMP9 enzyme activity has a prominent role in
      shedding of MICA/B. OBJECTIVES: To investigate the association between MMP9 (
      1562 C/T) polymorphism and serum MICA/B level in breast cancer patients. METHODS:
      In this case-control study, 105 patients with breast cancer and 100 healthy age
      matched women were selected from Yazd hospitals, Iran. The polymorphism of MMP9 (
      1562 C/T) was determined by PCR-RFLP. Concentration of MICB and MICA in the sera
      of breast cancer patients and healthy women were measured using ELISA method.
      RESULTS: The frequency of CC, CT and TT genotypes and T allele of the MMP9 (-1562
      C/T) did not show significant differences between breast cancer patients and
      healthy donors (p>0.05). On the other hand, the mean serum levels of MICB and
      MICA were significantly elevated in patients compared with healthy individuals
      (p<0.05). In patients with MMP9CC genotype, the mean serum MICB concentration was
      significantly higher than those patients with CT polymorphism (p<0.05). Although
      the mean of blood MICA concentration in patients with the CT genotype was higher
      than those patients with CC genotype, the difference was not statistically
      significant. CONCLUSION: The T allele of the MMP9 (-1562 C/T) does not show a
      correlation with serum levels of MICA and MICB in breast cancer patients.

PMID- 27026048
TI  - Immune Rebound: Multiple Sclerosis after Treatment of Cushing's Disease.
AB  - High cortisol level in endogenous Cushing's syndrome suppresses the immune system
      and after treatment there may be an over activity of immune reaction leading to
      autoimmune diseases mostly thyroid and rheumatologic disorders. This is the
      second reported case of multiple sclerosis developing after treatment of
      Cushing's syndrome. A 42-year old man is reported who presented with bone
      fracture and osteoporosis and diagnosed with Cushing's disease. Six months after
      surgical treatment of his pituitary adenoma, he developed progressive multiple
      sclerosis. We conclude that after treatment of endogenous Cushing's syndrome, the
      patients should be watched for development of autoimmune disorders including
      those affecting the central nervous system.

PMID- 27026049
TI  - Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes.
AB  - Hypothalamic astrocytes can respond to metabolic signals, such as leptin and
      insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin
      regulates appetite, adiposity and glucose metabolism, but little is known
      regarding the response of astrocytes to this orexigenic hormone. We have used
      both in vivo and in vitro approaches to demonstrate that acylated ghrelin (acyl
      ghrelin) rapidly stimulates glutamate transporter expression and glutamate uptake
      by astrocytes. Moreover, acyl-ghrelin rapidly reduces glucose transporter (GLUT)
      2 levels and glucose uptake by these glial cells. Glutamine synthetase and
      lactate dehydrogenase decrease, while glycogen phosphorylase and lactate
      transporters increase in response to acyl-ghrelin, suggesting a change in
      glutamate and glucose metabolism, as well as glycogen storage by astrocytes.
      These effects are partially mediated through ghrelin receptor 1A (GHSR-1A) as
      astrocytes do not respond equally to desacyl-ghrelin, an isoform that does not
      activate GHSR-1A. Moreover, primary astrocyte cultures from GHSR-1A knock-out
      mice do not change glutamate transporter or GLUT2 levels in response to acyl
      ghrelin. Our results indicate that acyl-ghrelin may mediate part of its metabolic
      actions through modulation of hypothalamic astrocytes and that this effect could
      involve astrocyte mediated changes in local glucose and glutamate metabolism that
      alter the signals/nutrients reaching neighboring neurons. 

PMID- 27026052
TI  - Government changes are jeopardising public health.

PMID- 27026051
TI  - Pleiotropic effects of the vacuolar ABC transporter MLT1 of Candida albicans on
      cell function and virulence.
AB  - Among the several mechanisms that contribute to MDR (multidrug resistance), the
      overexpression of drug-efflux pumps belonging to the ABC (ATP-binding cassette)
      superfamily is the most frequent cause of resistance to antifungal agents. The
      multidrug transporter proteins Cdr1p and Cdr2p of the ABCG subfamily are major
      players in the development of MDR in Candida albicans Because several genes
      coding for ABC proteins exist in the genome of C. albicans, but only Cdr1p and
      Cdr2p have established roles in MDR, it is implicit that the other members of the
      ABC family also have alternative physiological roles. The present study focuses
      on an ABC transporter of C. albicans, Mlt1p, which is localized in the vacuolar
      membrane and specifically transports PC (phosphatidylcholine) into the vacuolar
      lumen. Transcriptional profiling of the mlt1?/? mutant revealed a down-regulation
      of the genes involved in endocytosis, oxidoreductase activity, virulence and
      hyphal development. High-throughput MS-based lipidome analysis revealed that the
      Mlt1p levels affect lipid homoeostasis and thus lead to a plethora of
      physiological perturbations. These include a delay in endocytosis, inefficient
      sequestering of reactive oxygen species (ROS), defects in hyphal development and
      attenuated virulence. The present study is an emerging example where new and
      unconventional roles of an ABC transporter are being identified.

PMID- 27026053
TI  - Resolving the Phylogenetic Position of Coelacanth: The Closest Relative Is Not
      Always the Most Appropriate Outgroup.
AB  - Determining the phylogenetic relationship of two extant lineages of lobe-finned
      fish, coelacanths and lungfishes, and tetrapods is important for understanding
      the origin of tetrapods. We analyzed data sets from two previous studies along
      with a newly collected data set, each of which had varying numbers of species and
      genes and varying extent of missing sites. We found that in all the data sets the
      sister relationship of lungfish and tetrapods was constructed with the use of
      cartilaginous fish as the outgroup with a high degree of statistical support. In
      contrast, when ray-finned fish were used as the outgroup, which is taxonomically
      an immediate outgroup of lobe-finned fish and tetrapods, the sister relationship
      of coelacanth and tetrapods was supported most strongly, although the statistical
      support was weaker. Even though it is generally accepted that the closest
      relative is an appropriate outgroup, our analysis suggested that the large
      divergence of the ray-finned fish as indicated by their long branch lengths and
      different amino acid frequencies made them less suitable as an outgroup than
      cartilaginous fish. 

PMID- 27026054
TI  - Expansion Mechanisms and Evolutionary History on Genes Encoding DNA Glycosylases
      and Their Involvement in Stress and Hormone Signaling.
AB  - DNA glycosylases catalyze the release of methylated bases. They play vital roles
      in the base excision repair pathway and might also function in DNA demethylation.
      At least three families of DNA glycosylases have been identified, which included
      3'-methyladenine DNA glycosylase (MDG) I, MDG II, and HhH-GPD (Helix-hairpin
      Helix and Glycine/Proline/aspartate (D)). However, little is known on their
      genome-wide identification, expansion, and evolutionary history as well as their
      expression profiling and biological functions. In this study, we have genome
      widely identified and evolutionarily characterized these family members.
      Generally, a genome encodes only one MDG II gene in most of organisms. No MDG I
      or MDG II gene was detected in green algae. However, HhH-GPD genes were
      detectable in all available organisms. The ancestor species contain small size of
      MDG I and HhH-GPD families. These two families were mainly expanded through the
      whole-genome duplication and segmental duplication. They were evolutionarily
      conserved and were generally under purifying selection. However, we have detected
      recent positive selection among the Oryza genus, which might play roles in
      species divergence. Further investigation showed that expression divergence
      played important roles in gene survival after expansion. All of these family
      genes were expressed in most of developmental stages and tissues in rice plants.
      High ratios of family genes were downregulated by drought and fungus pathogen as
      well as abscisic acid (ABA) and jasmonic acid (JA) treatments, suggesting a
      negative regulation in response to drought stress and pathogen infection through
      ABA- and/or JA-dependent hormone signaling pathway. 

PMID- 27026050
TI  - Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of
      Neurotrophic Factors.
AB  - BACKGROUND: Shared connections between physical activity and neuroprotection have
      been studied for decades, but the mechanisms underlying this effect of specific
      exercise were only recently brought to light. Several evidences suggest that
      physical activity may be a reasonable and beneficial method to improve functional
      recovery in both peripheral and central nerve injuries and to delay functional
      decay in neurodegenerative diseases. In addition to improving cardiac and immune
      functions, physical activity may represent a multifunctional approach not only to
      improve cardiocirculatory and immune functions, but potentially modulating
      trophic factors signaling and, in turn, neuronal function and structure at times
      that may be critical for neurodegeneration and regeneration. METHODS: Research
      content related to the effects of physical activity and specific exercise
      programs in normal and injured nervous system have been reviewed. RESULTS:
      Sustained exercise, particularly if applied at moderate intensity and early after
      injury, exerts anti-inflammatory and pro-regenerative effects, and may boost
      cognitive and motor functions in aging and neurological disorders. However,
      newest studies show that exercise modalities can differently affect the
      production and function of brain-derived neurotrophic factor and other
      neurotrophins involved in the generation of neuropathic conditions. These
      findings suggest the possibility that new exercise strategies can be directed to
      nerve injuries with therapeutical benefits. CONCLUSION: Considering the growing
      burden of illness worldwide, understanding of how modulation of neurotrophic
      factors contributes to exercise-induced neuroprotection and regeneration after
      peripheral nerve and spinal cord injuries is a relevant topic for research, and
      represents the beginning of a new non-pharmacological therapeutic approach for
      better rehabilitation of neural disorders.

PMID- 27026055
TI  - Exploring the Psychological Profile of Patients with Delusional Infestation.
AB  - Delusional infestation (DI) is an uncommon psychiatric disorder in which patients
      present with the false and fixed belief (i.e. a delusion) that their skin and/or
      their environment is infested despite objective evidence to the contrary. Within
      psychodermatology specialist clinics there is a high rate of DI referrals. What
      is not known is the level of psychiatric and psychological co-morbidities
      associated with DI and whether psychiatric or psychological assessment would be
      warranted. One-hundred and thirty-eight adult patients with DI attending an
      outpatient psychodermatology clinic were given 3 standardised questionnaires. The
      results showed that 81% had a poor quality of life; 52% with anxiety, 41.6% with
      depression and 49% with appearance-related concerns. This study indicates high
      levels of psychiatric and psychological disorders in DI which require assessment
      and appropriate intervention.

PMID- 27026057
TI  - Evaluation of surgically assisted rapid maxillary expansion with and without
      midpalatal split.
AB  - The purpose of this study was to compare the efficacy and the patients'
      subjective symptomatology between surgically assisted rapid maxillary expansion
      (SARME) with midpalatal split and SARME without midpalatal split. The sample
      consisted of 24 consecutive adult patients requiring treatment with SARME, who
      were divided into two groups. Group 1 patients (n=14) underwent SARME with
      midpalatal split, and group 2 patients (n=10) underwent SARME without midpalatal
      separation. The efficacy of the technique was assessed in relation to the
      presence of a diastema between the upper incisors and radiographic evidence of
      separation of the maxillary bones in the midpalatal suture. The patients'
      symptomatology was evaluated using pain scores. The results demonstrated a
      greater efficacy for group 1 (P=0.00). The discomfort of surgery assessed
      immediately postoperative and at 14 days postoperative was similar in the two
      groups. Both surgical techniques were tolerated by the patients; the midpalatal
      separation did not influence patient discomfort due to surgery. The two groups
      showed a statistically significant difference regarding discomfort during
      appliance activation and pain during the postoperative phase, with group 2
      showing greater discomfort. 

PMID- 27026056
TI  - Adolescent Traumatic Brain Injury Induces Chronic Mesolimbic Neuroinflammation
      with Concurrent Enhancement in the Rewarding Effects of Cocaine in Mice during
      Adulthood.
AB  - Clinical psychiatric disorders of depression, anxiety, and substance abuse are
      most prevalent after traumatic brain injury (TBI). Pre-clinical research has
      focused on depression and anxiety post-injury; however, virtually no data exist
      examining whether the preference for illicit drugs is affected by traumatic
      injury in the developing adolescent brain. Using the controlled cortical impact
      (CCI) model of TBI and the conditioned place preference (CPP) assay, we tested
      the underlying hypothesis that brain injury during adolescence exacerbates the
      rewarding properties of cocaine in adulthood possibly through an active
      inflammatory status in the mesolimbic pathway. Six-week old, C57BL/6 mice
      sustained a single CCI-TBI to the right somatosensory cortex. CPP experiments
      with cocaine began 2 weeks post-TBI. Animals receiving cocaine displayed
      significant place preference shifts compared to saline controls. Further, within
      the cocaine-experienced cohort, moderate CCI-TBI during adolescence significantly
      increased the preference shift in adulthood when compared to naive controls.
      Additionally, persistent neuroinflammatory responses were observed in the cortex,
      nucleus accumbens (NAc), and ventral tegmental area post-CCI-TBI. Significant
      increases in both astrocytic, glial fibrillary acidic protein, and microglial,
      ionization basic acid 1, markers were observed in the NAc at the end of CPP
      testing. Moreover, analysis using focused array gene expression panels identified
      the upregulation of numerous inflammatory genes in moderate CCI-TBI animals,
      compared to naive controls, both in the cortex and NAc at 2 weeks post-TBI,
      before onset of cocaine administration. These results suggest that sustaining
      moderate TBI during adolescence may augment the rewarding effects of
      psychostimulants in adulthood, possibly by induction of chronic mesolimbic
      neuroinflammation.

PMID- 27026058
TI  - Local therapy in non-metastatic primary Ewing sarcoma of the mandible and maxilla
      in children.
AB  - Ewing sarcoma (ES) of the jaw bones comprises a small fraction of ES at all
      sites. Due to their rarity, a specific policy for local treatment is lacking. The
      aim of this study was to evaluate the local therapy for ES and recommend measures
      to individualize treatment options. Patients with primary non-metastatic ES of
      the jaw bones treated between August 2005 and February 2015 were analyzed. All
      patients received primary induction chemotherapy, following which lesions
      amenable to resection based on specific radiological criteria were resected;
      those with unresectable lesions were offered definitive radiotherapy. The maxilla
      was the primary site in 13 patients and the mandible in eight. The median age of
      patients was 11.6 years (range 5-17 years). Overall, surgery was performed in 17
      patients and definitive radiotherapy was used in four patients. Postoperative
      radiotherapy was administered to 12 patients and was avoided in five patients
      with 100% tumour necrosis. The 3-year overall survival, event-free survival, and
      local control were 68.1%, 63.6%, and 80.2%, respectively. Mandible primary and a
      histological response to chemotherapy were significant prognostic factors. The
      stratification of patients based on radiological criteria aids in selecting local
      therapy. In eligible patients, surgery with contemporary reconstruction results
      in optimal oncological and functional outcomes. Surgery also has the added
      advantage of identifying patients who may not need radiotherapy. 

PMID- 27026059
TI  - Clinical effects of an avocado-soybean unsaponifiable extract on arthralgia and
      osteoarthritis of the temporomandibular joint: preliminary study.
AB  - The aim of the present preliminary study was to investigate the effectiveness of
      an avocado-soybean unsaponifiable extract (ASU) in patients with arthralgia and
      osteoarthritis of the temporomandibular joint (TMJ). A randomized, double-blind,
      placebo-controlled trial was carried out. Fourteen women diagnosed with
      arthralgia and osteoarthritis of the TMJ using the Research Diagnostic Criteria
      for Temporomandibular Disorders were included in the statistical analysis. The
      women were allocated randomly to two groups: ASU group and placebo group. Pain
      was measured using a visual analogue scale and pressure algometer. Mandibular
      function was evaluated through measurement of mandibular movements. Quality of
      life was measured using the Oral Health Impact Profile (OHIP-14). The medication
      (ASU capsules or placebo capsules) was used for 4 months and the total follow-up
      was 6 months. Those taking the ASU extract had a decrease in pain symptoms and an
      improvement in quality of life. Moreover, a significant reduction in the use of
      rescue medication was found in the ASU group compared to the placebo group. This
      preliminary study provides strong evidence of the effectiveness of an avocado
      soybean unsaponifiable extract in patients with degenerative joint diseases and
      arthralgia in the TMJ. Further studies with larger samples should be performed. 

PMID- 27026060
TI  - e-MALDI: An Electrowetting-Enhanced Drop Drying Method for MALDI Mass
      Spectrometry.
AB  - The performance of matrix-assisted laser desorption ionization mass spectrometry
      (MALDI-MS) is frequently compromised by the heterogeneous distribution of matrix
      and analyte deposits on the target plate arising during the conventional drop
      drying sample preparation procedure. It was recently shown that this so-called
      coffee stain effect can be suppressed by exciting evaporating complex fluids
      throughout the drying process using AC-electrowetting. Here, we demonstrate that
      electrowetting-assisted drying of solutions of common MALDI matrix materials and
      a variety of common low molecular weight pharmaceutical molecules indeed leads to
      substantially smaller and more homogeneous sample spots on special electrowetting
      functionalized e-MALDI target plates. The improved spot quality enables 2-30*
      enhanced MALDI-MS signals along with substantial reductions of the typical
      lateral variations of the MALDI-MS. The latter largely eliminates the time
      consuming need to search for "sweet spots".

PMID- 27026061
TI  - [Management of benign melanocytic lesions as a melanoma prevention. Systematic
      review].
AB  - There is a growing concern and awareness of skin cancer. As a result, possibly
      unnecessary surgeries of melanocytic lesions are carried out as a prophylactic
      measure. We performed a systematic review of the medical literature to identify
      primary studies on the effectiveness and cost-effectiveness of surgery treatment
      of benign melanocytic lesions for melanoma prevention. We included 19 primary
      studies on surgical treatment of acquired melanocytic lesions and one economic
      evaluation. Indicators, such as number needed to treat and the malignancy ratio,
      depend on several factors such as specialty and experience of the physician,
      pressure from the patient or patient characteristics. Early diagnosis of melanoma
      is critical in preventing skin cancer. However, primary studies show through
      several indicators that there are factors that increase the proportion of lesions
      treated unnecessarily. Effectiveness can be improved by careful use of techniques
      to identify suspicious lesions and educational programs for physicians,
      especially in primary care. 

PMID- 27026062
TI  - Involvement of aspartoacylase in tremor expression in rats.
AB  - Essential tremor (ET) is a common movement disorder with a poorly understood
      etiology. The TRM/Kyo mutant rat, showing spontaneous tremor, is an animal model
      of ET. Recently, we demonstrated that tremors in these rats emerge when two
      mutant loci, a missense mutation in the hyperpolarization-activated cyclic
      nucleotide-gated potassium channel 1 (Hcn1) and the tremor (tm) deletion, are
      present simultaneously. However, we did not identify which gene within the tm
      deletion causes tremor expression in TRM/Kyo rats. A strong candidate among the
      13 genes within the tm deletion is aspartoacylase (Aspa), because some Aspa
      knockout mouse strains show tremor. Here, we generated Aspa-knockout rats using
      transcription activator-like effector nuclease technology and produced Aspa/Hcn1
      double-mutant rats by crossing Aspa-knockout rats with Hcn1-mutant rats. The Aspa
      knockout rats carried nonsense mutations in exon 4; and ASPA proteins were not
      detectable in their brain extracts. They showed elevated levels of N-acetyl-L
      aspartate (NAA) in urine and spongy vacuolation and abnormal myelination in the
      central nervous system, but no tremor. By contrast, Aspa/Hcn1 double-mutant rats
      spontaneously showed tremors resembling those in TRM/Kyo rats, and the tremor was
      suppressed by drugs therapeutic for ET but not for parkinsonian tremor. These
      findings indicated that the lack of the Aspa gene caused tremor expression in
      TRM/Kyo rats. Our animal model suggested that the interaction of NAA accumulation
      due to ASPA deficiency with an unstable neuronal membrane potential caused by
      HCN1 deficiency was involved in tremor development. 

PMID- 27026063
TI  - Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care
      Unit experience with smart pumps.
AB  - OBJECTIVES: To estimate the impact of smart pump implementation in a pediatric
      intensive care unit in terms of number and type of administration errors
      intercepted. DESIGN: Observational, prospective study carried out from January
      2010 to March 2015 with syringe and great volumen infusion pumps available in the
      hospital. SETTING: A tertiary level hospital pediatric intensive care unit.
      PARTICIPANTS: Infusions delivered with infusion pumps in all pediatric intensive
      care unit patients. INTERVENTIONS: Design of a drug library with safety limits
      for all intravenous drugs prescribed. MAIN VARIABLES: Users' compliance with drug
      library as well as number and type of errors prevented were analyzed. RESULTS:
      Two hundred and eighty-three errors were intercepted during 62 months of study. A
      high risk drug was involved in 58% of prevented errors, such as adrenergic
      agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids,
      potassium and insulin. Users' average compliance with the safety software was
      84%. CONCLUSIONS: Smart pumps implementation has proven effective in intercepting
      high risk drugs programming errors. These results might be exportable to other
      critical care units, involving pediatric or adult patients. Interdisciplinary
      colaboration is key to succeed in this process.

PMID- 27026064
TI  - Intracoronary thrombus in a patient with recurrent vasospasm: Findings of optical
      coherence tomography.

PMID- 27026067
TI  - X-linked Adrenal Hypoplasia Congenita Due to NR0B1 (DAX1) Deficiency Presenting
      as Severe Respiratory Distress in Near Term Infants.

PMID- 27026065
TI  - Ovarian cancer treatment with a tumor-targeting and gene expression-controllable
      lipoplex.
AB  - Overexpression of folate receptor alpha (FRalpha) and high telomerase activity
      are considered to be the characteristics of ovarian cancers. In this study, we
      developed FRalpha-targeted lipoplexes loaded with an hTERT promoter-regulated
      plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F
      LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized
      the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the
      MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro
      transfection assay, which was significantly increased compared with a non
      modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the
      growth of tumors and extended the survival of mice in a SKOV-3 tumor model
      compared with other groups. Such an anti-tumor effect was due to the increased
      expression of MP in tumor tissue, which led to the induction of tumor cell
      apoptosis, inhibition of tumor cell proliferation and suppression of tumor
      angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good
      safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRalpha
      targeted lipoplexes with therapeutic gene expression regulated by an hTERT
      promoter might be a promising gene therapy agent and a potential translational
      candidate for the clinical treatment of ovarian cancer. 

PMID- 27026068
TI  - A fatal complication of an incarcerated diaphragmatic hernia: pyo
      pneumopericardium due to a gastro-pericardial fistula Case report and literature
      review.
AB  - INTRODUCTION: The pyo-pneumopericardium is a very rare complication of an
      incarcerated diaphragmatic hernia. Usually, it depends on the existence of a
      gastropericardial fistula and, in most cases, it is a deadly complication. CASE
      REPORT: We present the case of a 65 year old man who was admitted to our
      emergency service with clinical signs of septic shock. With the help of the CT
      scan a pyo-pneumopericardium and incarcerated diaphragmatic hernia was diagnosed.
      He was subjected to emergency surgical intervention with double approach
      (thoracic and abdominal), discerning during surgery the existence of a
      pericardial abscess due to a gastro-pericardial fistula due to an incarcerated
      diaphragmatic hernia. The gastric fundus was resected with abolition of the
      gastro-pericardial fistula, evacuation of the pericardial abscess, performing the
      splenectomy (in order to have a better surgical access) and adequate treatment of
      the diaphragmatic hernia. Despite the medical efforts, the patient died on the
      10th postoperative day due to septic complications. To our knowledge this is the
      first case reported in the literature of gastro-pericardial fistula complicated
      with pyo-pneumo-pericardium due to an incarcerated diaphragmatic hernia. In such
      cases we consider that only by performing a double surgical approach (thoracic
      and abdominal) we can provide a proper resolution of the case, also based on the
      objective situation found during surgery, where the splenectomy can provide an
      easier approach to the diaphragmatic hernia. KEY WORDS: Diaphragmatic hernia,
      Gastropericardial fistula, Pyo-pneumopericardium.

PMID- 27026069
TI  - Boosting the power performance of multilayer graphene as lithium-ion battery
      anode via unconventional doping with in-situ formed Fe nanoparticles.
AB  - Graphene is extensively investigated and promoted as a viable replacement for
      graphite, the state-of-the-art material for lithium-ion battery (LIB) anodes,
      although no clear evidence is available about improvements in terms of cycling
      stability, delithiation voltage and volumetric capacity. Here we report the
      microwave-assisted synthesis of a novel graphene-based material in ionic liquid
      (i.e., carved multilayer graphene with nested Fe3O4 nanoparticles), together with
      its extensive characterization via several physical and chemical techniques. When
      such a composite material is used as LIB anode, the carved paths traced by the
      Fe3O4 nanoparticles, and the unconverted metallic iron formed in-situ upon the
      1(st) lithiation, result in enhanced rate capability and, especially at high
      specific currents (i.e., 5 A g(-1)), remarkable cycling stability (99% of
      specific capacity retention after 180 cycles), low average delithiation voltage
      (0.244 V) and a substantially increased volumetric capacity with respect to
      commercial graphite (58.8 Ah L(-1) vs. 9.6 Ah L(-1)).

PMID- 27026071
TI  - T cell responses: Autophagy maintains metabolic order.

PMID- 27026070
TI  - Triangular Black Phosphorus Atomic Layers by Liquid Exfoliation.
AB  - Few-layer black phosphorus (BP) is the most promising material among the two
      dimensional materials due to its layered structure and the excellent
      semiconductor properties. Currently, thin BP atomic layers are obtained mostly by
      mechanical exfoliation of bulk BP, which limits applications in thin-film based
      electronics due to a scaling process. Here we report highly crystalline few-layer
      black phosphorus thin films produced by liquid exfoliation. We demonstrate that
      the liquid-exfoliated BP forms a triangular crystalline structure on SiO2/Si
      (001) and amorphous carbon. The highly crystalline BP layers are faceted with a
      preferred orientation of the (010) plane on the sharp edge, which is an
      energetically most favorable facet according to the density functional theory
      calculations. Our results can be useful in understanding the triangular BP
      structure for large-area applications in electronic devices using two-dimensional
      materials. The sensitivity and selectivity of liquid-exfoliated BP to gas vapor
      demonstrate great potential for practical applications as sensors. 

PMID- 27026072
TI  - Autoimmunity: Nanoparticles engineered for antigen-specific immunotherapy.

PMID- 27026075
TI  - Primary caregivers of young children are unaware of food neophobia and food
      preference development.
AB  - Issues addressed: This research explored primary caregivers' awareness of food
      neophobia and how food preferences develop in young children aged between 1 and
      2.5 years. Methods: This qualitative study used case study methodology and
      comprised interviews with 24 primary caregivers of young children aged between 1
      and 2.5 years. Results and conclusions: Primary caregivers of young children are
      unaware of food neophobia and food preference development in young children. So
      what? Raising primary caregivers' awareness of food neophobia and how food
      preferences develop in young children may encourage caregivers to decrease their
      children's exposure to non-core foods.

PMID- 27026073
TI  - Immune responses to endogenous retroelements: taking the bad with the good.
AB  - The ultimate form of parasitism and evasion of host immunity is for the parasite
      genome to enter the germ line of the host species. Retroviruses have invaded the
      host germ line on the grandest scale, and this is evident in the extraordinary
      abundance of endogenous retroelements in the genome of all vertebrate species
      that have been studied. Many of these endogenous retroelements have retained
      viral characteristics; some also the capacity to replicate and, consequently, the
      potential to trigger host innate and adaptive immune responses. However, although
      retroelements are mainly recognized for their pathogenic potential, recent
      evidence suggests that this 'enemy within' may also have beneficial roles in
      tuning host immune reactivity. In this Review, we discuss how the immune system
      recognizes and is shaped by endogenous retroelements.

PMID- 27026074
TI  - T cell receptor signalling in the control of regulatory T cell differentiation
      and function.
AB  - Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal
      function in the control of self tolerance and inflammatory responses. Recent
      studies have revealed a discrete mode of T cell receptor (TCR) signalling that
      regulates TReg cell differentiation, maintenance and function and that affects
      gene expression, metabolism, cell adhesion and migration of these cells. Here, we
      discuss the emerging understanding of TCR-guided differentiation of TReg cells in
      the context of their function in health and disease.

PMID- 27026077
TI  - The Early Chain of Care in Patients with Bacteraemia with the Emphasis on the
      Prehospital Setting.
AB  - Purpose There is a lack of knowledge about the early phase of severe infection.
      This report describes the early chain of care in bacteraemia as follows: (a)
      compare patients who were and were not transported by the Emergency Medical
      Services (EMS); (b) describe various aspects of the EMS chain; and (c) describe
      factors of importance for the delay to the start of intravenous antibiotics. It
      was hypothesized that, for patients with suspected sepsis judged by the EMS
      clinician, the delay until the onset of antibiotic treatment would be shorter.
      Basic Procedures All patients in the Municipality of Gothenburg (Sweden) with a
      positive blood culture, when assessed at the Laboratory of Bacteriology in the
      Municipality of Gothenburg, from February 1 through April 30, 2012 took part in
      the survey. Main Findings/Results In all, 696 patients fulfilled the inclusion
      criteria. Their mean age was 76 years and 52% were men. Of all patients, 308
      (44%) had been in contact with the EMS and/or the emergency department (ED). Of
      these 308 patients, 232 (75%) were transported by the EMS and 188 (61%) had "true
      pathogens" in blood cultures. Patients who were transported by the EMS were
      older, included more men, and suffered from more severe symptoms and signs. The
      EMS nurse suspected sepsis in only six percent of the cases. These patients had a
      delay from arrival at hospital until the start of antibiotics of one hour and 19
      minutes versus three hours and 21 minutes among the remaining patients (P
      =.0006). The corresponding figures for cases with "true pathogens" were one hour
      and 19 minutes versus three hours and 15 minutes (P =.009). CONCLUSION: Among
      patients with bacteraemia, 75% used the EMS, and these patients were older,
      included more men, and suffered from more severe symptoms and signs. The EMS
      nurse suspected sepsis in six percent of cases. Regardless of whether or not
      patients with true pathogens were isolated, a suspicion of sepsis by the EMS
      clinician at the scene was associated with a shorter delay to the start of
      antibiotic treatment. Axelsson C , Herlitz J , Karlsson A , Sjoberg H , Jimenez
      Herrera M , Bang A , Jonsson A , Bremer A , Andersson H , Gellerstedt M ,
      Ljungstrom L . The early chain of care in patients with bacteraemia with the
      emphasis on the prehospital setting. Prehosp Disaster Med. 2016;31(3):272-277.

PMID- 27026076
TI  - Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic
      stem cell differentiation.
AB  - TAF4 (TATA-binding protein-associated factor 4) and its paralogue TAF4b are
      components of the TFIID core module. We inactivated the murine Taf4a gene to
      address Taf4 function during embryogenesis. Here we show that Taf4a(-/-) embryos
      survive until E9.5 where primary germ layers and many embryonic structures are
      identified showing Taf4 is dispensable for their specification. In contrast, Taf4
      is required for correct patterning of the trunk and anterior structures, ventral
      morphogenesis and proper heart positioning. Overlapping expression of Taf4a and
      Taf4b during embryogenesis suggests their redundancy at early stages. In
      agreement with this, Taf4a(-/-) embryonic stem cells (ESCs) are viable and
      comprise Taf4b-containing TFIID. Nevertheless, Taf4a(-/-) ESCs do not complete
      differentiation into glutamatergic neurons and cardiomyocytes in vitro due to
      impaired preinitiation complex formation at the promoters of critical
      differentiation genes. We define an essential role of a core TFIID TAF in
      differentiation events during mammalian embryogenesis. 

PMID- 27026078
TI  - Restoration gaps needed to exceed a threshold size to impede sealed lesion arrest
      in vitro.
AB  - OBJECTIVES: After selective excavation, bacteria are sealed beneath restorations.
      Leaking restorations could maintain carbohydrate-supply, leading to lesion
      progression and pulp damage. It is unclear if fluid (and thereby carbohydrate)
      exchange occurs through any interfacial gaps, or if such exchange only occurs in
      case gaps exceed a certain threshold size. We investigated how different
      restoration gap sizes impact on survival of sealed bacterial in vitro. METHODS:
      Bacterially contaminated artificial residual lesions were induced on the pulpo
      axial walls of standardized dentin micro-cavities using acetic-acid
      demineralization and a continuous-culture Lactobacillus rhamnosus biofilm-model.
      Adhesive restorations with different gap sizes (0/100/200/400 MUm) were placed
      (n=24/group). Restorations were submitted to cyclic loading (42 g/0.2 Hz) under
      highly cariogenic conditions in a mastication-simulating artificial mouth. After
      25 days, the number of sealed viable bacteria was determined as colony-forming
      units. RESULTS: After 25 days, CFU were significantly reduced in all groups (
      99.99%, p<0.001/Mann-Whitney). Significantly more viable bacteria remained in
      restorations with gaps >= 200 MUm (p<0.001). CONCLUSIONS: Restoration gaps needed
      to exceed a threshold size to impede lesion arrest in vitro. There is great need
      to better understand why such threshold exists and which factors (mastication
      forces, restoration material, lesion location) could moderate the observed
      association. CLINICAL SIGNIFICANCE: A certain gap sizes was necessary to allow
      sufficient fluid exchange for bacterial survival in vitro. It is not possible to
      deduct clinical recommendations at present.

PMID- 27026079
TI  - Using Eye Trackers for Usability Evaluation of Health Information Technology: A
      Systematic Literature Review.
AB  - BACKGROUND: Eye-tracking technology has been used to measure human cognitive
      processes and has the potential to improve the usability of health information
      technology (HIT). However, it is still unclear how the eye-tracking method can be
      integrated with other traditional usability methodologies to achieve its full
      potential. OBJECTIVE: The objective of this study was to report on HIT evaluation
      studies that have used eye-tracker technology, and to envision the potential use
      of eye-tracking technology in future research. METHODS: We used four reference
      databases to initially identify 5248 related papers, which resulted in only 9
      articles that met our inclusion criteria. RESULTS: Eye-tracking technology was
      useful in finding usability problems in many ways, but is still in its infancy
      for HIT usability evaluation. Limited types of HITs have been evaluated by eye
      trackers, and there has been a lack of evaluation research in natural settings.
      CONCLUSIONS: More research should be done in natural settings to discover the
      real contextual-based usability problems of clinical and mobile HITs using eye
      tracking technology with more standardized methodologies and guidance.

PMID- 27026080
TI  - Methylation and expression of Epstein-Barr virus latent membrane protein 1, 2A
      and 2B in EBV-associated gastric carcinomas and cell lines.
AB  - BACKGROUND: Promoter CpG methylation of Epstein-Barr virus (EBV) genome plays an
      essential role in maintaining viral latency. Latent membrane protein (LMP) 1, 2A
      and 2B of EBV exert multiple oncogenic properties by activating multiple signal
      pathways and modulating the expression of various oncogenes. AIMS: To study the
      methylation and expression of LMP1, 2A and LMP2B in EBV-positive cell lines and
      EBV-associated tumors. METHODS: The methylation profiles of LMP1p, LMP2Ap and
      LMP2Bp were evaluated by methylation-specific PCR (MSP) and bisulfite sequencing
      PCR (BSP), as well as their expression by quantitative real-time (qRT)-PCR in 41
      EBV-associated carcinomas (EBVaGCs) and 5 EBV-positive cell lines. RESULTS: All
      LMP promoters were methylated at different degrees in EBV-positive cell lines and
      hypermethylated in EBV-associated gastric carcinomas, while unmethylated LMP2Ap
      alleles were detected in B95-8 cell line. Following 5-aza-2'-deoxycytidine (5
      aza) treatment, the LMP1 expression was restored along with concomitant promoter
      demethylation; changes of LMP2A and LMP2B expression were different in different
      cells. CONCLUSION: Methylation of LMP1, 2A and 2B promoters mediates the
      silencing of LMP1, 2A and 2B in EBV-associated carcinomas and cell lines in
      varying degrees, and could be reactivated by demethylation agent and thus may
      contribute to the therapy of EBVaGCs.

PMID- 27026081
TI  - Serum transglutaminase 3 antibodies correlate with age at celiac disease
      diagnosis.
AB  - BACKGROUND: Transglutaminase (TG)2 is the autoantigen in celiac disease, but also
      TG3 antibodies have been detected in the serum of celiac disease patients. AIMS:
      To investigate the correlations between serum TG3 antibodies and clinical and
      histological manifestations of celiac disease and to assess gluten-dependency of
      TG3 antibodies. METHODS: Correlations between serum TG3 antibody levels measured
      from 119 adults and children with untreated coeliac disease and the demographic
      data, clinical symptoms, celiac antibodies, histological data and results of
      laboratory tests and bone mineral densities were tested. TG3 antibodies were
      reinvestigated in 97 celiac disease patients after 12 months on a gluten-free
      diet (GFD). RESULTS: TG3 antibody titers were shown to correlate with the age at
      celiac disease diagnosis. Further, negative correlation with TG3 antibodies and
      intestinal gammadelta+ cells at diagnosis and on GFD was detected. Correlations
      were not detected with the clinical manifestation of celiac disease, TG2 or
      endomysial autoantibodies, laboratory values, severity of mucosal villous
      atrophy, associated diseases or complications. TG3 antibody titers decreased on
      GFD in 56% of the TG3 antibody positive patients. CONCLUSION: Serum TG3 antibody
      positivity in celiac disease increases as the diagnostic age rises. TG3
      antibodies did not show similar gluten-dependency as TG2 antibodies.

PMID- 27026082
TI  - Alcoholic hepatitis histological score has high accuracy to predict 90-day
      mortality and response to steroids.
AB  - INTRODUCTION/OBJECTIVES: A histological classification system (AHHS) has been
      recently proposed to predict 90-day mortality in patients with alcoholic
      hepatitis (AH). We analyzed the spectrum of histological features in patients
      with AH and assessed the ability of AHHS for predicting both response to steroids
      and 90-day mortality. METHODS: Retrospective study of patients admitted to our
      tertiary centre between 2010 and 2014 with biopsy-proven AH. Histological
      features were analyzed and AHHS value was calculated. Kaplan-Meyer curves were
      calculated to assess the ability of AHHS to predict response to steroids and 90
      day mortality. RESULTS: We included 34 patients (70.6% men, mean age 48.5+/-8.9
      years). Transjugular liver biopsy was performed 3.5+/-2.9 days after admission.
      Presence of bilirubinostasis (p=0.049), degree of bilirubinostasis (p<0.001),
      absence of megamitochondria (p<0.001) and degree of polymorphonuclear
      infiltration (p=0.018) were significantly associated with higher mortality at 90
      days. Patients who responded to steroids had a significantly lower AHHS value
      than non-responders (5.4+/-0.9 vs 8.1+/-1.1, p=0.003). AAHS value was
      significantly higher in patients who died compared to patients who survived at 90
      days (9.0+/-0.7 vs 5.0+/-0.9, p<0.001). AHHS predicted response to steroids
      [AUROC 0.90 (CI95% 0.742-1.000), p=0.004] and 90-day mortality [AUROC 1.0 (CI95%
      1.0-1.0), p<0.001] with high accuracy. CONCLUSIONS: In this cohort of patients,
      presence and degree of bilirubinostasis, absence of megamitochondria and degree
      of PMN infiltration were significantly associated with 90-day mortality. AHHS had
      a high accuracy for predicting response to steroids and 90-day mortality in this
      cohort of patients.

PMID- 27026083
TI  - Diversity in photosynthetic electron transport under [CO2]-limitation: the
      cyanobacterium Synechococcus sp. PCC 7002 and green alga Chlamydomonas
      reinhardtii drive an O2-dependent alternative electron flow and non-photochemical
      quenching of chlorophyll fluorescence during CO2-limited photosynthesis.
AB  - Some cyanobacteria, but not all, experience an induction of alternative electron
      flow (AEF) during CO2-limited photosynthesis. For example, Synechocystis sp. PCC
      6803 (S. 6803) exhibits AEF, but Synechococcus elongatus sp. PCC 7942 does not.
      This difference is due to the presence of flavodiiron 2 and 4 proteins (FLV2/4)
      in S. 6803, which catalyze electron donation to O2. In this study, we observed a
      low-[CO2] induced AEF in the marine cyanobacterium Synechococcus sp. PCC 7002
      that lacks FLV2/4. The AEF shows high affinity for O2, compared with AEF mediated
      by FLV2/4 in S. 6803, and can proceed under extreme low [O2] (about a few uM O2).
      Further, the transition from CO2-saturated to CO2-limited photosynthesis leads a
      preferential excitation of PSI to PSII and increased non-photochemical quenching
      of chlorophyll fluorescence. We found that the model green alga Chlamydomonas
      reinhardtii also has an O2-dependent AEF showing the same affinity for O2 as that
      in S. 7002. These data represent the diverse molecular mechanisms to drive AEF in
      cyanobacteria and green algae. In this paper, we further discuss the diversity,
      the evolution, and the physiological function of strategy to CO2-limitation in
      cyanobacterial and green algal photosynthesis.

PMID- 27026084
TI  - Effect of a long-term high-protein diet on survival, obesity development, and gut
      microbiota in mice.
AB  - Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined
      with either high or low protein-to-sucrose ratios during their entire lifespan to
      examine the long-term effects on obesity development, gut microbiota, and
      survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated
      obesity and reduced survival relative to mice fed a low-fat diet. By contrast,
      intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong
      weight gain and adipose tissue expansion, and survival was not significantly
      altered relative to low-fat-fed mice. Our findings support the notion that
      reduced survival in response to high-fat/high-sucrose feeding is linked to
      obesity development. Digital gene expression analyses, further validated by qPCR,
      demonstrated that the protein/sucrose ratio modulated global gene expression over
      time in liver and adipose tissue, affecting pathways related to metabolism and
      inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract
      Chip revealed significant changes in the composition of the gut microbiota in
      relation to host age and dietary fat content, but not the protein/sucrose ratio.
      Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a
      major driver shaping the gut microbiota, whereas the effect of a high-fat diet on
      survival is dependent on the protein/sucrose ratio. 

PMID- 27026085
TI  - Peripheral, but not central, GLP-1 receptor signaling is required for improvement
      in glucose tolerance after Roux-en-Y gastric bypass in mice.
AB  - Roux-en-Y gastric bypass (RYGB) causes profound weight loss and remission of
      diabetes by influencing metabolic physiology, yet the mechanisms behind these
      clinical improvements remain undefined. After RYGB, levels of glucagon-like
      peptide-1 (GLP-1), a hormone that enhances insulin secretion and promotes
      satiation, are substantially elevated. Because GLP-1 signals in both the
      periphery and the brain to influence energy balance and glucose regulation, we
      aimed to determine the relative requirements of these systems to weight loss and
      improved glucose tolerance following RYGB surgery in mice. By pharmacologically
      blocking peripheral or central GLP-1R signaling, we examined whether GLP-1 action
      is necessary for the metabolic improvements observed after RYGB. Diet-induced
      obese mice underwent RYGB or sham operation and were implanted with osmotic pumps
      delivering the GLP-1R antagonist exendin-(9-39) (2 pmol.kg(-1).min(-1)
      peripherally; 0.5 pmol.kg(-1).min(-1) centrally) for up to 10 wk. Blockade of
      peripheral GLP-1R signaling partially reversed the improvement in glucose
      tolerance after RYGB. In contrast, fasting glucose and insulin sensitivity, as
      well as body weight, were unaffected by GLP-1R antagonism. Central GLP-1R
      signaling did not appear to be required for any of the metabolic improvements
      seen after this operation. Collectively, these results suggest a detectable but
      only modest role for GLP-1 in mediating the effects of RYGB and that this role is
      limited to its well-described action on glucose regulation.

PMID- 27026086
TI  - Thyroid hormone receptor-beta1 signaling is critically involved in regulating
      secondary ossification via promoting transcription of the Ihh gene in the
      epiphysis.
AB  - Thyroid hormone (TH) action is mediated through two nuclear TH receptors,
      THRalpha and THRbeta. Although the role of THRalpha is well established in bone,
      less is known about the relevance of THRbeta-mediated signaling in bone
      development. On ther basis of our recent finding that TH signaling is essential
      for initiation and formation of secondary ossification center, we evaluated the
      role of THRs in mediating TH effects on epiphysial bone formation. Two-day
      treatment of TH-deficient Tshr(-/-) mice with TH increased THRbeta1 mRNA level
      3.4-fold at day 7 but had no effect on THRalpha1 mRNA level at the proximal tibia
      epiphysis. Treatment of serum-free cultures of tibias from 3-day-old mice with T3
      increased THRbeta1 expression 2.1- and 13-fold, respectively, at 24 and 72 h. Ten
      day treatment of Tshr(-/-) newborns (days 5-14) with THRbeta1 agonist GC1 at 0.2
      or 2.0 MUg/day increased BV/TV at day 21 by 225 and 263%, respectively, compared
      with vehicle treatment. Two-day treatment with GC1 (0.2 MUg/day) increased
      expression levels of Indian hedgehog (Ihh) 100-fold, osterix 15-fold, and
      osteocalcin 59-fold compared with vehicle at day 7 in the proximal tibia
      epiphysis. Gel mobility shift assay demonstrated that a putative TH response
      element in the distal promoter of mouse Ihh gene interacted with THRbeta1. GC1
      treatment (1 nM) increased Ihh distal promoter activity 20-fold after 48 h in
      chondroctyes. Our data suggest a novel role for THRbeta1 in secondary
      ossification at the epiphysis that involves transcriptional upregulation of Ihh
      gene.

PMID- 27026088
TI  - Carcinoid syndrome produced by an isolated metastase in femoral nerve from a
      midgut carcinoid tumor.

PMID- 27026087
TI  - Effects of transcutaneous electrical nerve stimulation (TENS) on arterial
      stiffness and blood pressure in resistant hypertensive individuals: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Resistant hypertension (RH) treatment requires an adequate and
      intense therapeutic approach. However, the results are not always satisfactory
      despite intensive treatment. Of the different pathophysiological mechanisms
      involved in the pathogenesis of RH, sympathetic overstimulation and therapies
      that block the sympathetic system have been widely studied. These approaches,
      however, are invasive and expensive. Another possible approach is by
      transcutaneous electrical nerve stimulation (TENS), a noninvasive method that
      modulates activity by using low-frequency transcutaneous electrical stimulation
      to inhibit primary afferent pathways. Thus, the current study will evaluate the
      effect of applying TENS in the cervicothoracic region of subjects with RH and
      will seek to develop a new low-cost and readily available therapy to treat this
      group of hypertensive individuals. METHODS/DESIGN: This is a randomized, single
      blind (subject), parallel-assignment study controlled with a sham group and
      including participants aged 40 to 70 years with resistant hypertension. The trial
      has two arms: the treatment and control (sham group). The treatment group will be
      submitted to the stimulation procedure (TENS). The sham group will not be
      submitted to stimulation. The primary outcomes will be a reduction in the
      peripheral blood pressure and adverse events. The secondary outcomes will be a
      reduction the central blood pressure. The study will last 30 days. The sample
      size was calculated assuming an alpha error of 5 % to reject the null hypothesis
      with a statistical power of 80 %, thereby resulting in 28 participants per group
      (intervention versus sham). DISCUSSION: In recent decades, RH has become very
      common and costly. Adequate control requires several drugs, and in many cases,
      treatment is not successful. Sympathetic nervous system inhibition by renal
      denervation and central inhibition have significant effects in reducing BP;
      however, these treatments are costly and invasive. Another type of sympathetic
      nervous system inhibition can also be noninvasively achieved by electric current.
      Therefore, the application of TENS may be a new therapeutic option for treating
      resistant hypertensive individuals. TRIAL REGISTRATION: Clinical Trials
      NCT02365974.

PMID- 27026090
TI  - Timely exercise for controlling glucose and oxidative stress. Reply to Chacko E.
      [letter].

PMID- 27026089
TI  - Colorectal cancer in Crohn's colitis is comparable to sporadic colorectal cancer.
AB  - PURPOSE: It is now recognized that Crohn's disease (CD), similar to ulcerative
      colitis (UC), carries an up to 20-fold higher cancer risk, and the development of
      colorectal carcinoma (CRC) is a major long-term complication. Once CRC is
      present, molecular profiling is one of the components in selecting appropriate
      treatment strategies; however, in contrast to UC, genetic alterations in Crohn's
      colitis-associated CRC are poorly understood. METHODS: In a series of 227
      patients with Crohn's colitis, we identified 33 cases of CRC (~14 %) and
      performed targeted mutational analysis of BRAF/KRAS/NRAS and determined
      microsatellite status as well as immunophenotype of the tumors. RESULTS: In the
      CRC cohort, the median age at time of cancer diagnosis was 58 (range 34-77 vs.
      59.5 in sporadic; P = 0.81) and the median CD duration was 29 years (range 6-45).
      As a group, CRC complicating Crohn's colitis is BRAF (97 %) and NRAS (100 %) wild
      type and the vast majority is microsatellite stable (94 %); KRAS-mutations were
      found in six cases (18 %). Stage grouping, anatomic distribution, and overall
      survival were similar to sporadic CRC; however, long-standing CD (>=25 years) as
      well as gastric-immunophenotype (MUC5AC+) was associated with significantly
      shorter overall survival (P = 0.0029; P = 0.036, respectively). CONCLUSION: In
      summary, the clinicopathological and molecular profile of CD-associated CRC is
      similar to that observed in sporadic CRC.

PMID- 27026091
TI  - Hip hemiarthroplasty for femur neck fractures: minimally invasive direct anterior
      approach versus postero-lateral approach.
AB  - BACKGROUND: The minimally invasive direct anterior approach (MDAA) has been
      reported to be useful in total hip arthroplasty. The benefits of this approach
      may be useful for the treatment of femoral neck fractures. Aim of this study is
      to compare MDAA and postero-lateral approach (PLA) in patients treated with hip
      hemiarthroplasty for femoral neck fractures. MATERIALS AND METHODS: Between 2013
      and 2014, 109 patients underwent bipolar hip hemiarthroplasty for femoral neck
      fracture: 88 female and 21 male with a mean age of 88 years old. PLA was
      performed in 54 cases and MDAA in 55 cases. RESULTS: The mean surgery time was
      significantly lower in MDAA group (P = 0.001). The hemoglobin loss was
      significantly lower in MDAA group (P = 0.02). The mean postoperative pain was
      significantly lower in the MDAA group (P = 0.001). The mean hospitalization
      period was 2 days lower in the MDAA group but with no significant difference
      between the two groups (P = 0.09). Hip dislocation was higher in PLA cases (7.4
      %) than in MDAA cases (1.8 %). Periprosthetic fracture occurred only in one case
      of PLA. Great trochanter fracture occurred in 1 MDAA cases, while no cases were
      observed in the PLA group. CONCLUSIONS: Minimally invasive direct anterior
      approach for hip hemiarthroplasty in elderly people with femoral neck fracture
      provided significant benefit in the early postoperative period when compared to
      the postero-lateral approach in terms of surgery time, hemoglobin loss,
      postoperative pain, time of recovery and dislocation rate. LEVEL OF EVIDENCE:
      Therapeutic study, level IV (case series).

PMID- 27026093
TI  - Polish scientists among the most influential scientific minds in 2015.

PMID- 27026094
TI  - Neutrophil-to-lymphocyte ratio: a new prognostic factor even in patients with
      heart failure.

PMID- 27026092
TI  - Impact of Comorbidities on Acute Injury and Recovery in Preclinical Stroke
      Research: Focus on Hypertension and Diabetes.
AB  - Human ischemic stroke is very complex, and no single preclinical model can
      comprise all the variables known to contribute to stroke injury and recovery.
      Hypertension, diabetes, and hyperlipidemia are leading comorbidities in stroke
      patients. The use of predominantly young adult and healthy animals in
      experimental stroke research has created a barrier for translation of findings to
      patients. As such, more and more disease models are being incorporated into the
      research design. This review highlights the major strengths and weaknesses of the
      most commonly used animal models of these conditions in preclinical stroke
      research. The goal is to provide guidance in choosing, reporting, and executing
      appropriate disease models that will be subjected to different models of stroke
      injury.

PMID- 27026095
TI  - Periostin as a biomarker of airway inflammation.

PMID- 27026096
TI  - Aortic stenosis: new pathophysiological mechanisms and future perspectives for
      pharmacological therapy.

PMID- 27026097
TI  - In Vivo study of naturally deformed Escherichia coli bacteria.
AB  - A combination of light-microscopy and image processing has been applied to study
      naturally deformed Escherichia coli under in vivo condition and at the order of
      sub-pixel high-resolution accuracy. To classify deflagellated non-dividing E.
      coli cells to the rod-shape and bent-shape, a geometrical approach has been
      applied. From the analysis of the geometrical data which were obtained of image
      processing, we estimated the required effective energy for shaping a rod-shape to
      a bent-shape with the same size. We evaluated the energy of deformation in the
      naturally deformed bacteria with minimum cell manipulation, under in vivo
      condition, and with minimum influence of any external force, torque and pressure.
      Finally, we have also elaborated on the possible scenario to explain how
      naturally deformed bacteria are formed from initial to final-stage.

PMID- 27026098
TI  - Erythrocyte-mediated delivery of recombinant enzymes.
AB  - The possibility to clone, express and purify recombinant enzymes have originated
      the opportunity to dispose of a virtually infinite array of proteins that could
      be used in the clinics to treat several inherited and acquired pathological
      conditions. However, the direct administration of these recombinant proteins
      faces some intrinsic difficulties, such as degradation by circulating proteases
      and/or inactivation by the patient immune system. The use of drug delivery
      systems may overcome these limitations. Concerning recombinant enzyme therapy,
      the present review will mainly focus on the exploitation of erythrocytes as a
      carrier system for enzymes removing potentially noxious metabolites from the
      circulation, either as limiting treatment strategy for auxotrophic tumours or as
      a detoxing approach for some intoxication type inherited metabolic disorders.
      Moreover, the possibility of using RBCs as a potential delivering system
      addressing the enzymes to the monocyte-macrophages of reticular endothelial
      system for the treatment of diseases associated with this cell lineage, e.g.
      lysosome storage diseases, will be briefly discussed.

PMID- 27026099
TI  - Impact of stress on oocyte quality and reproductive outcome.
AB  - Stress is an important factor that affects physical and mental status of a
      healthy person disturbing homeostasis of the body. Changes in the lifestyle are
      one of the major causes that lead to psychological stress. Psychological stress
      could impact the biology of female reproduction by targeting at the level of
      ovary, follicle and oocyte. The increased level of stress hormone such as
      cortisol reduces estradiol production possibly by affecting the granulosa cell
      functions within the follicle, which results deterioration in oocyte quality.
      Adaptation of lifestyle behaviours may generate reactive oxygen species (ROS) in
      the ovary, which further affects female reproduction. Balance between level of
      ROS and antioxidants within the ovary are important for maintenance of female
      reproductive health. Physiological level of ROS modulates oocyte functions, while
      its accumulation leads to oxidative stress (OS). OS triggers apoptosis in
      majority of germ cells within the ovary and even in ovulated oocytes. Although
      both mitochondria- as well as death-receptor pathways are involved in oocyte
      apoptosis, OS-induced mitochondria-mediated pathway plays a major role in the
      elimination of majority of germ cells from ovary. OS in the follicular fluid
      deteriorates oocyte quality and reduces reproductive outcome. On the other hand,
      antioxidants reduce ROS levels and protect against OS-mediated germ cell
      apoptosis and thereby depletion of germ cells from the ovary. Indeed, OS is one
      of the major factors that has a direct negative impact on oocyte quality and
      limits female reproductive outcome in several mammalian species including human. 

PMID- 27026100
TI  - Lacustrine Arcellinina (Testate Amoebae) as Bioindicators of Arsenic
      Contamination.
AB  - Arcellininids (testate amoebae) were examined from 61 surface sediment samples
      collected from 59 lakes in the vicinity of former gold mines, notably Giant Mine,
      near Yellowknife, Northwest Territories, Canada to determine their utility as
      bioindicators of arsenic (As), which occurs both as a byproduct of gold
      extraction at mines in the area and ore-bearing outcrops. Cluster analysis (Q-R
      mode) and detrended correspondence analysis (DCA) reveal five arcellininid
      assemblages, three of which are related to varying As concentrations in the
      sediment samples. Redundancy analysis (RDA) showed that 14 statistically
      significant environmental parameters explained 57 % of the variation in faunal
      distribution, while partial RDA indicated that As had the greatest influence on
      assemblage variance (10.7 %; p < 0.10). Stress-indicating species (primarily
      centropyxids) characterized the faunas of samples with high As concentrations
      (median = 121.7 ppm, max > 10000 ppm, min = 16.1 ppm, n = 32), while difflugiid
      dominated assemblages were prevalent in substrates with relatively low As
      concentrations (median = 30.2 ppm, max = 905.2 ppm, min = 6.3 ppm, n = 20). Most
      of the lakes with very high As levels are located downwind (N and W) of the
      former Giant Mine roaster stack where refractory ore was roasted and substantial
      quantities of As were released (as As2O3) to the atmosphere in the first decade
      of mining. This spatial pattern suggests that a significant proportion of the
      observed As, in at least these lakes, are industrially derived. The results of
      this study highlight the sensitivity of Arcellinina to As and confirm that the
      group has considerable potential for assessing the impact of As contamination on
      lakes.

PMID- 27026101
TI  - The Truffle Microbiome: Species and Geography Effects on Bacteria Associated with
      Fruiting Bodies of Hypogeous Pezizales.
AB  - Fungi that produce their fruiting bodies underground within the soil profile are
      known commonly as truffles. Truffle fruiting bodies harbor a diverse but poorly
      understood microbial community of bacteria, yeasts, and filamentous fungi. In
      this study, we used next-generation 454 amplicon pyrosequencing of the V1 and V4
      region of the bacterial 16S ribosomal DNA (rDNA) in order to characterize and
      compare effects of truffle species and geographic origin on the truffle
      microbiome. We compared truffle microbiomes of the glebal tissue for eight
      truffle species belonging to four distinct genera within the Pezizales: Tuber,
      Terfezia, Leucangium, and Kalapuya. The bacterial community within truffles was
      dominated by Proteobacteria, Bacterioides, Actinobacteria, and Firmicutes.
      Bacterial richness within truffles was quite low overall, with between 2-23
      operational taxonomic units (OTUs). Notably, we found a single Bradyrhizobium OTU
      to be dominant within truffle species belonging to the genus Tuber, irrespective
      of geographic origin, but not in other truffle genera sampled. This study offers
      relevant insights into the truffle microbiome and raises questions concerning the
      recruitment and function of these fungal-associated bacteria consortia.

PMID- 27026102
TI  - Extracranial-intracranial bypass for internal carotid/middle cerebral
      atherosclerotic steno-occlusive diseases in conjunction with carotid
      endarterectomy for contralateral cervical carotid stenosis: clinical results and
      cognitive performance.
AB  - Clinical results as well as cognitive performances after extracranial to
      intracranial (EC-IC) bypass in conjunction with contralateral carotid
      endarterectomy (CEA) are poorly understood. Data from 14 patients who underwent
      unilateral EC-IC bypass for atherosclerotic internal carotid artery (ICA)/middle
      cerebral artery (MCA) steno-occlusive disease in conjunction with CEA for
      contralateral cervical carotid stenosis were retrospectively reviewed.
      Postoperative results were evaluated by MRI imagings. Nine patients also
      underwent neuropsychological examinations (NPEs), including assessment by the
      Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale
      Revised (WMS-R) before and about 6 months after bilateral surgeries.
      Postoperative MRI follow-up (median, 8 months; interquartile range, 7-8 months)
      confirmed successful bypass in all patients, with no additional ischemic lesions
      on T2WI when compared with preoperative imaging. Further, MRA showed patent
      bypass and contralateral smooth patency at CEA portion in all patients. In the
      group rate analysis, all five postoperative NPE scores (Verbal IQ, Performance
      IQ, WMS-memory, WMS-attention, and Average scores of all those four scores) were
      improved relative to preoperative NPE scores. Performance IQ and Average score
      improvements were statistically significant. Clinical results after EC-IC bypass
      in conjunction with contralateral CEA were feasible. Based on the group rate
      analysis, we conclude that successful unilateral EC-IC bypass and contralateral
      carotid endarterectomy does not adversely affect postoperative cognitive
      function. 

PMID- 27026103
TI  - Identification of Low-Level Product-Related Variants in Filgrastim Products
      Presently Available in Highly Regulated Markets.
AB  - BACKGROUND: Filgrastim is a recombinant, non-glycosylated form of human
      granulocyte colony-stimulating factor, used to stimulate leukocyte proliferation
      in patients suffering from neutropenia. Since the expiration of patents
      associated with Amgen's filgrastim biopharmaceutical, Neupogen((r)), in 2006, a
      number of filgrastim products have been marketed; however, a detailed
      characterization and comparison of variants associated with these products have
      not been publically reported. OBJECTIVE: The objective of this study was to
      identify and quantify product-related variants in filgrastim reference products
      and biosimilars thereof that are presently available in highly regulated markets.
      METHODS: In this study, we used intact and top-down mass spectrometry to identify
      and quantify product-related variants in filgrastim products. Mass spectrometry
      has become the method of choice for physicochemical characterization of
      biopharmaceuticals, allowing accurate and sensitive characterization of product
      related variants. RESULTS: In addition to modifications ubiquitously present in
      biopharmaceuticals, such as methionine oxidation and asparagine/glutamine
      deamidation, we identified six different low-level, product-related variants
      present in some, but not all, of the tested products. Two variants, an acetylated
      filgrastim variant and a filgrastim variant containing an additional C-terminal
      tryptophan extension, are newly identified variants. CONCLUSION: This study
      demonstrates that filgrastim products already in widespread clinical use in
      highly regulated markets differ in low-level, product-related variants present at
      levels mostly below 1 % relative abundance. This study provides a comprehensive
      catalog of minor differences between filgrastim products and suggests that the
      filgrastim product-related variants described here are not clinically relevant
      when present at low abundance.

PMID- 27026104
TI  - Hippocampal abnormalities and sudden childhood death.

PMID- 27026105
TI  - Phylogenetic characterization of a novel herpesvirus found in the liver and lungs
      of a Chilean flamingo (Phoenicopterus chilensis).
AB  - A novel herpesvirus was detected in a 17-day-old Chilean flamingo (Phoenicopterus
      chilensis) with pneumonia, hepatopathy, and severe anemia that was housed in
      California. Postmortem examination identified a pale, enlarged liver, mildly
      increased fluid in the lungs, and red foci in the spleen. Histologic examination
      revealed marked hepatic necrosis with syncytia, splenic necrosis, and
      interstitial pneumonia with eosinophilic intranuclear inclusions within
      hepatocytes and in unidentified cells of the lung. Transmission electron
      microscopy identified virions consistent with a herpesvirus in the nucleus and
      cytoplasm of degenerative hepatocytes. Nested consensus PCR, sequencing, and
      phylogenetic analysis identified a novel herpesvirus within the genus Iltovirus
      in the subfamily Alphaherpesvirinae. 

PMID- 27026106
TI  - Histology and immunohistochemistry of severe inflammatory bowel disease versus
      lymphoma in the ferret (Mustela putorius furo).
AB  - Inflammatory bowel disease (IBD) is a common disorder of ferrets (Mustela
      putorius furo) that may progress to lymphoma. Although routine histology is used
      to distinguish between these diseases, misclassifications may occur.
      Immunohistochemistry (IHC) is commonly used to distinguish between IBD and
      lymphoma in small animals. The objective of our study was to determine the
      agreement in the diagnosis reached solely using hematoxylin and eosin (HE)
      stained, full-thickness sections versus using a combination of HE and IHC.
      Enteric sections from 44 ferrets previously diagnosed with IBD or intestinal
      lymphoma and 3 control ferrets were analyzed by pathologists with expertise in
      ferrets. A pathologist blinded to the original diagnosis assessed the same HE
      stained sections. Analysis was then repeated using HE sections in parallel with
      sections stained using antibodies against CD3 and CD79a. No significant
      difference was found between the original HE diagnosis and the HE diagnosis
      reached by the blinded pathologist (p = 0.91) or between the blinded
      pathologist's HE versus HE with IHC diagnosis (p = 0.16). In the 2 cases where
      disagreement was present, IHC was pivotal in reaching a final diagnosis. There
      was no significant age (p = 0.29) difference between diagnoses; however,
      significantly more male ferrets were affected with IBD than females (p = 0.004).
      Immunophenotype of the lymphoma was not correlated with predilection for location
      in the intestinal wall (p = 0.44). Results suggest that although IHC is not
      necessary to distinguish IBD from intestinal lymphoma in ferrets, it can be
      useful a definitive diagnosis in cases of severe IBD. 

PMID- 27026107
TI  - Establishment of a quantitative real-time PCR for the detection of Pneumocystis
      carinii f. sp. suis in bronchoalveolar lavage samples from pigs.
AB  - Respiratory diseases in pigs are mostly polymicrobial, and the involved pathogens
      can vary from farm to farm. The impact of Pneumocystis carinii (P. c.) f. sp.
      suis on respiratory disorders has not been comprehensively appraised because
      tests were limited to lung tissue samples and, for this reason, it was not
      possible to detect the fungus in living animals. In the present study,
      bronchoalveolar lavage fluid (BALF) from 12 pigs and oral fluid samples from 9
      pigs were tested for the presence of Pneumocystis by quantitative real-time PCR.
      The results from these 2 clinical specimens were compared with Pneumocystis
      quantities in lung tissue samples. Pneumocystis quantities in BALF correlated
      significantly to those in lung tissue. BALF has proved to be an adequate specimen
      for detection of various respiratory pathogens in pigs, and the collection
      procedure directly on farms is also well established. In contrast to the BALF
      results, all oral fluid samples were negative. Thus, specimens from the lower
      respiratory tract should generally be preferred for the detection of Pneumocystis
      Additionally, under farm conditions, oral fluid is mainly collected in the form
      of collective samples per pen. In the present study, oral swab sampling of
      individual pigs was intended but failed in 3 of 12 pigs because they did not
      salivate sufficiently. As a conclusion, only BALF can be recommended as a useful
      tool for Pneumocystis herd monitoring in vivo. 

PMID- 27026108
TI  - Expression of serotonin, chromogranin-A, serotonin receptor-2B, tryptophan
      hydroxylase-1, and serotonin reuptake transporter in the intestine of dogs with
      chronic enteropathy.
AB  - Serotonin regulates many intestinal motor and sensory functions. Altered
      serotonergic metabolism has been described in human gastrointestinal diseases.
      The objective of our study was to compare expression of several components of the
      serotonergic system [serotonin (5-HT), serotonin reuptake transporter protein
      (SERT), tryptophan hydroxylase-1 (TPH-1), 5-HT receptor2B (5-HT2B)] and the
      enterochromaffin cell marker chromogranin-A (CgA) in the intestinal mucosa
      between dogs with chronic enteropathy and healthy controls. Serotonin and CgA
      expression were determined by immunohistochemistry using banked and prospectively
      obtained, paraffin-embedded canine gastrointestinal biopsies (n = 11), and
      compared to a control group of canine small intestinal sections (n = 10).
      Expression of SERT, TPH-1, and 5-HT2B were determined via real-time reverse
      transcription (qRT)-PCR using prospectively collected endoscopic duodenal
      biopsies (n = 10) and compared to an additional control group of control duodenal
      biopsies (n = 8, control group 2) showing no evidence of intestinal inflammation.
      Dogs with chronic enteropathies showed strong staining for both 5-HT and CgA.
      Mean positive cells per high power field (HPF) were significantly increased for
      both compounds in dogs with chronic enteropathies (p < 0.001 for 5-HT; p < 0.05
      for CgA). The number of 5-HT-positive and CgA-positive cells/HPF showed
      significant correlation in the entire group of dogs, including both diseased and
      healthy individuals (Pearson r(2) = 0.2433, p = 0.016). No significant
      differences were observed for SERT, TPH-1, or 5-HT2B expression; however, dogs
      with chronic enteropathy showed greater variability in expression of TPH-1 and 5
      HT2B We conclude that components of the neuroendocrine system show altered
      expression in the intestinal mucosa of dogs with chronic enteropathy. These
      changes may contribute to nociception and clinical signs in these patients. 

PMID- 27026109
TI  - Rapid stress-induced transcriptomic changes in the brain depend on beta
      adrenergic signaling.
AB  - Acute exposure to stressful experiences can rapidly increase anxiety and cause
      neuropsychiatric disorders. The effects of stress result in part from the release
      of neurotransmitters and hormones, which regulate gene expression in different
      brain regions. The fast neuroendocrine response to stress is largely mediated by
      norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a
      slower and more sustained release of corticosterone. While corticosterone is an
      important regulator of gene expression, it is not clear which stress-signals
      contribute to the rapid regulation of gene expression observed immediately after
      stress exposure. Here, we demonstrate in mice that 45 min after an acute swim
      stress challenge, large changes in gene expression occur across the transcriptome
      in the hippocampus, a region sensitive to the effects of stress. We identify
      multiple candidate genes that are rapidly and transiently altered in both males
      and females. Using a pharmacological approach, we show that most of these rapidly
      induced genes are regulated by NE through beta-adrenergic receptor signaling. We
      find that CRH and corticosterone can also contribute to rapid changes in gene
      expression, although these effects appear to be restricted to fewer genes. These
      results newly reveal a widespread impact of NE on the transcriptome and identify
      novel genes associated with stress and adrenergic signaling.

PMID- 27026111
TI  - Effect of education on non-specific neck and low back pain: A meta-analysis of
      randomized controlled trials.

PMID- 27026112
TI  - Response to letter to the editor: 'Physical examination tests for screening and
      diagnosis of cervicogenic headache: A systematic review'.

PMID- 27026113
TI  - Palladium-catalyzed silylation reaction between benzylic halides and
      silylboronate.
AB  - An efficient Pd-catalyzed silylation reaction of benzylic halides with
      silylboronate is reported. In this reaction, primary and secondary benzylic
      halides could react well with silylboronates to afford benzylic silanes. This
      reaction accommodates a broad substrate scope and proceeds smoothly under very
      mild reaction conditions. The corresponding products could be obtained in
      moderate to high yields and with stereospecificity. 

PMID- 27026110
TI  - Effects of lack of microRNA-34 on the neural circuitry underlying the stress
      response and anxiety.
AB  - Stress-related psychiatric disorders, including anxiety, are complex diseases
      that have genetic, and environmental causes. Stressful experiences increase the
      release of prefrontal amygdala neurotransmitters, a response that is relevant to
      cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicits
      anxiety-like behavior and dendritic remodeling in the amygdala. Members of the
      miR-34 family have been suggested to regulate synaptic plasticity and
      neurotransmission processes, which mediate stress-related disorders. Using mice
      that harbored targeted deletions of all 3 members of the miR-34-family (miR-34
      TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic and
      medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo
      microdialysis. Moreover, we also examined fear conditioning/extinction, stress
      induced anxiety, and dendritic remodeling in the BLA of stress-exposed TKO mice.
      We found that TKO mice showed resilience to stress-induced anxiety and
      facilitation in fear extinction. Accordingly, no significant increase was evident
      in aminergic prefrontal or amygdala GABA release, and no significant acute stress
      induced amygdalar dendritic remodeling was observed in TKO mice. Differential
      GRM7, 5-HT2C, and CRFR1 mRNA expression was noted in the mpFC and BLA between TKO
      and WT mice. Our data demonstrate that the miR-34 has a critical function in
      regulating the behavioral and neurochemical response to acute stress and in
      inducing stress-related amygdala neuroplasticity.

PMID- 27026114
TI  - Gondwanian relicts and oceanic dispersal in a cosmopolitan radiation of euedaphic
      ground beetles.
AB  - Anillini are a tribe of minute, euedaphic ground beetles (Carabidae)
      characterized by the loss of eyes, loss of wings and high levels of local
      endemism. Despite their presumed low dispersal, they have a nearly cosmopolitan
      distribution, including isolated islands such as New Zealand and New Caledonia.
      We used a time calibrated molecular phylogeny to test, first, if the tribe as
      currently understood is monophyletic and, second, whether the time of divergence
      is compatible with an early vicariant diversification after the breakup of
      Gondwana. We sequenced portions of 6 mitochondrial and 3 nuclear genes for 66
      specimens in 17 genera of Anillini plus 39 outgroups. The resulting phylogenetic
      tree was used to estimate the time of diversification using two independent
      calibration schemes, by applying molecular rates for the related genus Carabus or
      by dating the tree with fossil and geological information. Rates of molecular
      evolution and lineage ages were mostly concordant between both calibration
      schemes. The monophyly of Anillini was well-supported, and its age was consistent
      with a Gondwanian origin of the main lineages and an initial diversification at
      ca. 100Ma representing the split between the eyed Nesamblyops (New Zealand) and
      the remaining Anillini. The subsequent diversification, including the split of
      the Nearctic Anillinus and the subsequent splits of Palaearctic lineages, was
      dated to between 80 and 100Ma and thus was also compatible with a tectonic
      vicariant origin. On the contrary, the estimated age of the New Caledonian blind
      Orthotyphlus at ca. 30+/-20Ma was incompatible with a vicariant origin,
      suggesting the possibility of trans-oceanic dispersal in these endogean beetles.

PMID- 27026117
TI  - Year in Review.

PMID- 27026115
TI  - Evolutionary history of the river frog genus Amietia (Anura: Pyxicephalidae)
      reveals extensive diversification in Central African highlands.
AB  - The African river frog genus Amietia is found near rivers and other lentic water
      sources throughout central, eastern, and southern Africa. Because the genus
      includes multiple morphologically conservative species, taxonomic studies of
      river frogs have been relatively limited. We sampled 79 individuals of Amietia
      from multiple localities in and near the Albertine Rift (AR) of Burundi,
      Democratic Republic of the Congo, and Uganda. We utilized single-gene (16S) and
      concatenated (12S, 16S, cyt b and RAG1) gene-tree analyses and coalescent species
      tree analyses to construct phylogenetic trees. Two divergence dating approaches
      were used in BEAST, including secondary calibration points with 12S, 16S, cyt b
      and RAG1, and a molecular clock with the 12S, 16S, and cyt b genes. All analyses
      recovered Amietia as monophyletic with strong support, and revealed several well
      supported cryptic lineages, which is consistent with other recent phylogeography
      studies of AR amphibians. Dating estimates were similar, and Amietia
      diversification is coincident with global cooling and aridification events in the
      Miocene and Pliocene, respectively. Our results suggest additional taxonomic work
      is needed to describe multiple new species of AR Amietia, some of which have
      limited geographic distributions that are likely to be of conservation concern.

PMID- 27026118
TI  - Complication Rates in Altitude Restricted Patients Following Aeromedical
      Evacuation.
AB  - INTRODUCTION: Military aeromedical evacuation, especially that associated with
      the present Middle East conflict, is seeing increasing research. This ecological
      study initiates research into the validating flight surgeon by looking at cabin
      altitude restriction (CAR), arguably the validating flight surgeon's prescription
      with the highest patient-mission impact, and its association with postflight
      complications. METHODS: CAR rates from January 2006 through February 2008 were
      determined from the U.S. Transportation Command Regulating and Command and
      Control Evacuation System database. Postflight complication rates-the rate of
      patients with postflight complications (PFC) and the postflight complications per
      100 patients (PFC-100)-from January 2007 through June 2008 were calculated from
      the Landstuhl Regional Medical Center trauma database. CAR and complication rates
      were examined before, during, and after the authors' deployment. In addition, the
      relationship between CAR and postflight complication rates was investigated; as
      the rates were nonlinear, a Spearman correlation was performed. RESULTS: CAR
      rates during the authors' deployments were significantly up compared to the
      authors' predecessors or successors; their predecessors and successors did not
      differ statistically. Likewise, the PFC rate during the authors' deployments was
      significantly lower than that of the before or after time frames. Furthermore, a
      statistically significant inverse relationship between CAR and PFC rates
      (Spearman rho = -0.587) as well as CAR and PFC-100 rates (Spearman rho = -0.568)
      was demonstrated. DISCUSSION: CAR rate was inversely correlated to PFC and PFC
      100 rates. This finding suggests that aggressive prescribing of CARs may have a
      salutary effect on postflight complication rates and bears further investigation.

PMID- 27026119
TI  - Motion Sickness and Resting Energy Expenditure in Chinese Male Adults.
AB  - BACKGROUND: Motion sickness can influence energy homeostasis by enhancing
      thermolysis. This study tested the hypothesis that resting energy expenditure
      (REE), as the major component of thermogenesis, might also play a role during
      motion sickness. METHODS: The effect of seasickness on REE at sea was examined in
      71 healthy Chinese male volunteers. Change in REE, heart rate variability (HRV),
      blood ghrelin levels, and leptin levels were observed across baseline, voyage,
      and recovery stages. Seasickness severity was assessed using the Graybiel motion
      sickness questionnaire (GMSQ), and the nausea syndrome rating (NSR) of each
      participant was also evaluated. REE was examined by indirect calorimetry. HRV was
      derived from the electrocardiogram to analyze cardiac sympathovagal activity.
      Blood ghrelin and leptin levels were tested by radioimmunoassay. RESULTS: In
      subjects with severe seasickness during the voyage, the GMSQ and NSR scores were
      higher than in subjects with slight and moderate seasickness. The REE declined
      significantly compared to baseline and recovery levels and was lower than in
      subjects with slight and moderate seasickness. Cardiac sympathetic activity was
      significantly decreased, while vagal activity was increased. Plasma ghrelin
      levels were also significantly increased and were negatively correlated with the
      measured REE levels and positively correlated with NSR as well as change of HRV
      LF/HF ratio from baseline. DISCUSSION: Severe motion sickness induces REE
      suppression, which may be attributed to dramatic alteration of sympathovagal
      activity and plasma ghrelin levels in humans.

PMID- 27026120
TI  - Prediction of Lunar- and Martian-Based Intra- and Site-to-Site Task Performance.
AB  - BACKGROUND: This study aimed to investigate the feasibility of determining the
      physiological parameters associated with the ability to complete simulated
      exploration type tasks at metabolic rates which might be expected for lunar and
      Martian ambulation. METHODS: Running VO2max and gas exchange threshold (GET) were
      measured in 21 volunteers. Two simulated extravehicular activity field tests were
      completed in 1 G in regular athletic apparel at two intensities designed to
      elicit metabolic rates of ~20.0 and ~30.0 ml . kg(-1) . min(-1), which are
      similar to those previously reported for ambulation in simulated lunar- and
      Martian-based environments, respectively. RESULTS: All subjects were able to
      complete the field test at the lunar intensity, but 28% were unable to complete
      the field test at the Martian intensity (non-Finishers). During the Martian field
      test there were no differences in VO2 between Finishers and non-Finishers, but
      the non-Finishers achieved a greater %VO2max compared to Finishers (78.4 +/- 4.6%
      vs. 64.9 +/- 9.6%). Logistic regression analysis revealed fitness thresholds for
      a predicted probability of 0.5, at which Finishing and non-Finishing are equally
      likely, and 0.75, at which an individual has a 75% chance of Finishing, to be a
      VO2max of 38.4 ml . kg(-1) . min(-1) and 40.0 ml . kg(-1) . min(-1) or a GET of
      20.1 ml . kg(-1) . min(-1) and 25.1 ml . kg(-1) . min(-1), respectively (chi(2) =
      10.2). Logistic regression analysis also revealed that the expected %VO2max
      required to complete a field test could be used to successfully predict
      performance (chi(2) = 19.3). DISCUSSION: The results of the present investigation
      highlight the potential utility of VO2max, particularly as it relates to the
      metabolic demands of a surface ambulation, in defining successful completion of
      planetary-based exploration field tests.

PMID- 27026121
TI  - Physiological Indices of Pilots' Abilities Under Varying Task Demands.
AB  - INTRODUCTION: This study investigated pilots' ability by examining the effects of
      flight experience and task demand on physiological reactions, and analyzing the
      diagnostic meanings underlying correlated parameters. METHOD: A total of 12
      experienced pilots and 12 less experienced pilots performed 4 simulated flight
      tasks, including normal and emergency situations. Fixation duration (FD), saccade
      rate (SR), blink rate (BR), heart rate (HR), respiration rate (RR), and
      respiration amplitude (RA) were measured during the tasks. RESULTS: More
      experienced pilots adapted their SR flexibly to changing task demands and had
      significantly lower SR than less experienced pilots during emergency tasks (29.6
      +/- 20.0 vs. 70.1 +/- 67.1 saccades/min). BR, HR, and RR were affected by pilot
      experience but not by task demand. More experienced pilots had lower BR, HR, and
      RR than less experienced pilots during both normal tasks (BR: 14.3 +/- 13.0 vs.
      32.9 +/- 25.8 blinks/min; HR: 72.7 +/- 7.9 vs. 83.2 +/- 7.2 bpm; RR: 15.4 +/- 2.1
      vs. 19.5 +/- 5.2 breaths/min) and emergency tasks (BR: 10.2 +/- 5.0 vs. 32.3 +/-
      20.8 blinks/min; HR: 73.3 +/- 7.3 vs. 82.2 +/- 11.6 bpm; RR: 15.6 +/- 1.9 vs.
      18.0 +/- 3.2 breaths/min). FD and RA were not sensitive to either flight
      experience or task demand. CONCLUSIONS: Physiological reactions have the
      potential to reflect pilots' ability from different aspects. SR and BR could
      indicate pilots' differences in information access strategy. HR and RR could
      reflect a pilot's physical fitness. These findings are useful for understanding a
      pilot's ability.

PMID- 27026122
TI  - A Performance Comparison of Color Vision Tests for Military Screening.
AB  - BACKGROUND: Current color vision (CV) tests used for aviation screening in the
      U.S. Army only provide pass-fail results, and previous studies have shown
      variable sensitivity and specificity. The purpose of this study was to evaluate
      seven CV tests to determine an optimal CV test screener that potentially could be
      implemented by the U.S. Army. METHODS: There were 133 subjects [65 Color Vision
      Deficits (CVD), 68 Color Vision Normal (CVN)] who performed all of the tests in
      one setting. CVD and CVN determination was initially assessed with the Oculus
      anomaloscope. Each test was administered monocularly and according to the test
      protocol. The main outcome measures were test sensitivity, specificity, and
      administration time (automated tests). RESULTS: Three of the four
      Pseudoisochromatic Plate (PIP) tests had a sensitivity/specificity > 0.90 OD/OS,
      whereas the FALANT tests had a sensitivity/specificity > 0.80 OD/OS. The Cone
      Contrast Test (CCT) demonstrated sensitivity/specificity > 0.90 OD/OS, whereas
      the Color Assessment and Diagnosis (CAD) test demonstrated
      sensitivity/specificity > 0.85 OD/OS. Comparison with the anomaloscope ("gold
      standard") revealed no significant difference of sensitivity and specificity
      OD/OS with the CCT, Dvorine PIP, and PIPC tests. Finally, the CCT administration
      time was significantly faster than the CAD test. DISCUSSION: The current U.S.
      Army CV screening tests demonstrated good sensitivity and specificity, as did the
      automated tests. In addition, some current PIP tests (Dvorine, PIPC), and the CCT
      performed no worse statistically than the anomaloscope with regard to
      sensitivity/specificity. The CCT letter presentation is randomized and results
      would not be confounded by potential memorization, or fading, of book plates.

PMID- 27026123
TI  - Suicide and Murder-Suicide Involving Aircraft.
AB  - BACKGROUND: This is a systematic review of suicide and homicide-suicide events
      involving aircraft. In aeromedical literature and in the media, these very
      different events are both described as pilot suicide, but in psychiatry they are
      considered separate events with distinct risk factors. METHODS: Medical
      databases, internet search engines, and aviation safety databases were searched
      in a systematic way to obtain relevant cases. Relevant articles were searched for
      additional references. RESULTS: There were 65 cases of pilot suicide and 6 cases
      of passengers who jumped from aircraft found. There were also 18 cases of
      homicide-suicide found involving 732 deaths. Pilots perpetrated 13 homicide
      suicide events. Compared to non-aviation samples, a large percentage of pilot
      suicides in this study were homicide-suicides (17%). DISCUSSION: Homicide-suicide
      events occur extremely rarely. However, their impact in terms of the proportion
      of deaths is significant when compared to deaths from accidents. There is
      evidence of clustering where pilot suicides occur after by media reports of
      suicide or homicide-suicide. Five of six homicide-suicide events by pilots of
      commercial airliners occurred after they were left alone in the cockpit. This,
      along with a sixth incident in which active intervention by a Japan Air crew
      saved 147 lives, suggests that having two flight members in the cockpit is
      potentially protective. No single factor was associated with the risk for suicide
      or homicide-suicide. Factors associated with both events included legal and
      financial crises, occupational conflict, mental illness, and relationship
      stressors. Drugs and/or alcohol played a role in almost half of suicides, but not
      in homicide-suicides.

PMID- 27026124
TI  - Design and Human Factors of Therapeutic Hyperbaric Chambers.
AB  - INTRODUCTION: Hyperbaric therapeutic chambers are pressure vessels capable of
      accommodating one or more persons with the purpose of providing medical
      treatment. Therapeutic hyperbaric chambers have been in use from the mid-20(th)
      century, yet apparently their design has not reached their full potential and
      they are not compatible with current healthcare facilities design. This paper
      will present therapeutic hyperbaric chambers from a human-environment-machine
      perspective in order to highlight their specific problems and requirements, and
      suggest design concepts that may improve patient satisfaction, quality of
      treatment, and functionality of the staff. Data were collected from a literature
      review, a market survey, and personal observations. Main design solutions include
      personal space and privacy, stress- and anxiety-reducing environments, hazard
      mitigation, rearrangement of seating, and personalized (user-tailored)
      entertainment systems. It is suggested that adopting a user-centered design
      rather than an engineering focus will increase satisfaction and overall 'user
      experience' of the patients, alleviate psychological issues, and lessen workload
      and improve functionality of the staff. This study could be applicable and easily
      adapted to other confined therapeutic environments in which patients are
      restrained for several hours on a regular basis in receiving treatment, such as
      dialysis or chemotherapy rooms, and for confined nonmedical situations such as
      aircrafts and rapid trains.

PMID- 27026125
TI  - Lessons from a Space Analog on Adaptation for Long-Duration Exploration Missions.
AB  - BACKGROUND: Exploration missions to asteroids and Mars will bring new challenges
      associated with communication delays and more autonomy for crews. Mission safety
      and success will rely on how well the entire system, from technology to the human
      elements, is adaptable and resilient to disruptive, novel, or potentially
      catastrophic events. The recent NASA Extreme Environment Missions Operations
      (NEEMO) 20 mission highlighted this need and produced valuable "lessons learned"
      that will inform future research on team adaptation and resilience. METHODS: A
      team of NASA, industry, and academic members used an iterative process to design
      a tripod shaped structure, called the CORAL Tower, for two astronauts to assemble
      underwater with minimal tools. The team also developed assembly procedures,
      administered training to the crew, and provided support during the mission.
      RESULTS: During the design, training, and assembly of the Tower, the team learned
      first-hand how adaptation in extreme environments depends on incremental testing,
      thorough procedures and contingency plans that predict possible failure
      scenarios, and effective team adaptation and resiliency for the crew and support
      personnel. DISCUSSION: Findings from NEEMO 20 provide direction on the design and
      testing process for future space systems and crews to maximize adaptation. This
      experience also underscored the need for more research on team adaptation,
      particularly how input and process factors affect adaption outcomes, the team
      adaptation iterative process, and new ways to measure the adaptation process.

PMID- 27026126
TI  - A Novel Treatment of Fear of Flying Using a Large Virtual Reality System.
AB  - BACKGROUND: Fear of flying (FoF), a common phobia in the developed world, is
      usually treated with cognitive behavioral therapy, most efficiently when combined
      with exposure methods, e.g., virtual reality exposure therapy (VRET). We
      evaluated FoF treatment using VRET in a large motion-based VR system. The treated
      subjects were seated on a moving platform. The virtual scenery included the
      interior of an aircraft and a window view to the outside world accompanied by
      platform movements simulating, e.g., takeoff, landing, and air turbulence.
      Relevant auditory stimuli were also incorporated. CASE REPORT: Three male
      patients with FoF underwent a clinical interview followed by three VRETs in the
      presence and with the guidance of a therapist. Scores on the Flight Anxiety
      Situation (FAS) and Flight Anxiety Modality (FAM) questionnaires were obtained on
      the first and fourth visits. Anxiety levels were assessed using the subjective
      units of distress (SUDs) scale during the exposure. All three subjects expressed
      satisfaction regarding the procedure and did not skip or avoid any of its stages.
      Consistent improvement was seen in the SUDs throughout the VRET session and
      across sessions, while patients' scores on the FAS and FAM showed inconsistent
      trends. Two patients participated in actual flights in the months following the
      treatment, bringing 12 and 16 yr of avoidance to an end. DISCUSSION: This VR
      based treatment includes critical elements for exposure of flying experience
      beyond visual and auditory stimuli. The current case reports suggest VRET
      sessions may have a meaningful impact on anxiety levels, yet additional research
      seems warranted.

PMID- 27026127
TI  - Development of a Field-Deployable Psychomotor Vigilance Test to Monitor
      Helicopter Pilot Performance.
AB  - INTRODUCTION: Flying a helicopter is a complex psychomotor skill. Fatigue is a
      serious threat to operational safety, particularly for sustained helicopter
      operations involving high levels of cognitive information processing and
      sustained time on task. As part of ongoing research into this issue, the object
      of this study was to develop a field-deployable helicopter-specific psychomotor
      vigilance test (PVT) for the purpose of daily performance monitoring of pilots.
      METHODS: The PVT consists of a laptop computer, a hand-operated joystick, and a
      set of rudder pedals. Screen-based compensatory tracking task software includes a
      tracking ball (operated by the joystick) which moves randomly in all directions,
      and a second tracking ball which moves horizontally (operated by the rudder
      pedals). The 5-min test requires the pilot to keep both tracking balls centered.
      RESULTS: This helicopter-specific PVT's portability and integrated data
      acquisition and storage system enables daily field monitoring of the performance
      of individual helicopter pilots. The inclusion of a simultaneous foot-operated
      tracking task ensures divided attention for helicopter pilots as the movement of
      both tracking balls requires simultaneous inputs. DISCUSSION: This PVT is quick,
      economical, easy to use, and specific to the operational flying task. It can be
      used for performance monitoring purposes, and as a general research tool for
      investigating the psychomotor demands of helicopter operations. While reliability
      and validity testing is warranted, data acquired from this test could help
      further our understanding of the effect of various factors (such as fatigue) on
      helicopter pilot performance, with the potential of contributing to helicopter
      operational safety.

PMID- 27026128
TI  - Applications of 3D Printing in Austere Environments.

PMID- 27026129
TI  - You're the Flight Surgeon. A complication of surgical vision correction.

PMID- 27026131
TI  - This Month in Aerospace Medicine History.

PMID- 27026130
TI  - You're the Flight Surgeon. Malaria prevention in U.S. Air Force aviators.

PMID- 27026132
TI  - This Month in Aerospace Medicine History.

PMID- 27026133
TI  - Prevalence of intestinal helminthic infections and malnutrition among
      schoolchildren of the Zegie Peninsula, northwestern Ethiopia.
AB  - A cross-sectional study involving 408 schoolchildren was performed from November
      2013 to February 2014 to assess the prevalence of intestinal helminthic
      infections and malnutrition among schoolchildren of the Zegie Peninsula,
      northwestern Ethiopia. A structured questionnaire was used to gather data on the
      demographic and risk factors associated with intestinal helminthic infections.
      Stool samples were collected and examined for helminth eggs using the formalin
      ether concentration technique. In addition, anthropometric measurements were
      performed to assess the nutritional status of the schoolchildren. The overall
      prevalence of intestinal helminthic infections in the study area was 69.1%.
      Single, double, triple, and quadruple infections were 42.2%, 18.4%, 5.9%, and
      0.7%, respectively. The prevalence of hookworm, Schistosoma mansoni, Ascaris
      lumbricoides, Trichuris trichiura, Hymenolepis nana, and Strongyloides
      stercoralis infections were 43.4%, 29.9%, 12.7%, 10%, 4.6%, and 0.7%,
      respectively. The prevalence of malnutrition in terms of stunting, being
      underweight, and wasting were 15.3%, 18%, and 27.6%, respectively. However, no
      significant association was found between intestinal helminthic infections and
      stunting, being underweight and wasting (p>0.05). It can be concluded that
      intestinal helminthic infections, specifically infections due to hookworm and S.
      mansoni, are important health problems among schoolchildren of the Zegie
      Peninsula.

PMID- 27026134
TI  - Synergism between Pfcrt and Pfmdr1 genes could account for the slow recovery of
      chloroquine sensitive Plasmodium falciparum strains in Ghana after chloroquine
      withdrawal.
AB  - Unlike other countries, the chloroquine resistant marker Pfcrt T76 mutant has
      remained fairly stable in Ghana several years after official disuse of
      chloroquine. Certain mutations in Pfmdr1 may potentiate Pfcrt T76, offering a
      possible explanation for this observation. To understand the phenomenon, the co
      existence of mutations in Pfmdr1 with Pfcrt T76 in Ghanaian Plasmodium falciparum
      isolates was studied. The reported presence of parasites with reduced sensitivity
      to amodiaquine and quinine in the country was also studied. Blood samples
      collected from confirmed malaria patients presenting at health facilities in two
      distinct ecological zones were analyzed. The prevalence of Pfcrt K76T and the
      five point mutations in Pfmdr1 were determined using nested PCR followed by RFLP
      analysis. The association between genes was determined by chi square analysis,
      and synergism between the two genes was ascertained using the Jonckheere-Terptra
      (J-T) test followed by Monte Carlo simulation (MCS). Nearly fifty-four percent
      (53.7%) of the P. falciparum isolates examined had the Pfcrt T76 gene, out of
      which 18.3% had both K76 and T76 alleles. Mutations at codon 86, 184, 1034, 1042
      and 1246 of the Pfmdr1 gene were detected in 36.0%, 87.9%, 71.0%, 91.6% and 8.4%
      of the isolates, respectively. The haplotypes of Pfmdr1 present were NFCDD
      (43.46%), YFCDD (27.57%), NFSDD (7.48%), NYSNY (5.14%) and YFSDD (4.67%). Pfcrt
      T76 was significantly associated with a double mutation at codon 86 and 184 of
      Pfmdr1 (YF; chi2=18.045, p=0.006). Associations were observed between Pfcrt K76T
      and Pfmdr1 triple mutation at codons 86, 184 and 1034 (NFC; chi2=13.770, p=0.032
      and YFC; chi2=16.489, p=0.011). The J-T test showed significant synergism between
      Pfcrt 76 and Pfmdr1 polymorphisms (p<0.0001), which was confirmed by MCS at 99%
      CI. Synergism between Pfcrt and Pfmdr1 mutant genes could account for the slow
      recovery of chloroquine sensitive P. falciparum in Ghana. The same phenomenon
      could explain resistance to amodiaquine and quinine. The outcomes of this study
      also indicated a possible emergence of artemether-lumefantrine resistance in
      Ghana.

PMID- 27026135
TI  - Susceptibility, likelihood to be diagnosed, worry and fear for contracting Lyme
      disease.
AB  - Risk perception and psychological concerns are relevant for understanding how
      people view Lyme disease. This study investigates the four separate outcomes of
      susceptibility, likelihood to be diagnosed, worry, and fear for contracting Lyme
      disease. University students (n=713) were surveyed about demographics, perceived
      health, Lyme disease knowledge, Lyme disease preventive behaviors, Lyme disease
      history, and Lyme disease miscellaneous variables. We found that women were
      associated with increased susceptibility and fear. Asian/Asian-American
      race/ethnicity was associated with increased worry and fear. Perceived good
      health was associated with increased likelihood to be diagnosed, worry, and fear.
      Correct knowledge was associated with increased susceptibility and likelihood to
      be diagnosed. Those who typically spend a lot of time outdoors were associated
      with increased susceptibility, likelihood to be diagnosed, worry, and fear. In
      conclusion, healthcare providers and public health campaigns should address
      susceptibility, likelihood to be diagnosed, worry, and fear about Lyme disease,
      and should particularly target women and Asians/Asian-Americans to address any
      possible misconceptions and/or offer effective coping strategies.

PMID- 27026136
TI  - Hydrogenations and electric field induced magnetic behaviors in armchair silicene
      nanoribbons.
AB  - Using the first-principles calculations, we investigate the geometric, electronic
      and magnetic properties of armchair silicene nanoribbons with different edge
      hydrogenations. Our results show that the interesting magnetic behaviors such as
      the bipolar magnetic semiconductor can be found. Moreover, the addition of the
      transverse electric field can modulate the bipolar magnetic semiconductor to half
      metal or spin-splitting metal. And the spin-up electrons are localized at one
      edge, the spin-down holes localized at the opposite edge under the external
      electric field. These results may present a new avenue for band engineering of
      silicene nanoribbons and benefit the design of silicon-based nano-spin-devices in
      nanoelectronics. 

PMID- 27026137
TI  - Protective effect of Geraniol on the transgenic Drosophila model of Parkinson's
      disease.
AB  - The role of Geraniol was studied on the transgenic Drosophila model flies
      expressing normal human alpha synuclein (h-alphaS) in the neurons. Geraniol at
      final concentration of 10, 20 and 40MUM were mixed in the diet and the flies were
      allowed to feed on it for 24 days. The effect of geraniol was studied on the
      climbing ability, activity pattern, lipid peroxidation, protein carbonyl,
      glutathione, dopamine content, and glutathione-S-transferase activity in the
      brains of transgenic Drosophila. The exposure of PD model flies to 10, 20 and
      40MUM of geraniol results in a significant delay in the loss of climbing ability
      (p<0.05), improved activity pattern reduced the oxidative stress (p<0.05) in the
      brains of transgenic Drosophila as compared to unexposed PD model flies. The
      results suggest that geraniol is potent in reducing the PD symptoms in transgenic
      Drosophila model of Parkinson's disease. 

PMID- 27026138
TI  - LETTERA DEL DIRETTORE.
AB  - In nearly three decades to the direction of the journal Annali Italiani di
      Chirurgia I could add to my personal experiences as surgeon and University
      Professor of Surgery, those very special in the rather different field of
      scientific literature from the specific point of view of Chief Editor - English
      term that identifies the "Director" of a scientific journal. The original wish to
      enhance and promote the qualities of researches and professional activity of
      Italian surgery within the journal, after an initial phase of normal management
      has expanded ambitiously, and over the last decade has been taken new editorial
      strategic decisions to promote more and more the cultural value and the diffusion
      of the magazine, for the benefit of its subscribers and its readers. Therefore,
      since 2007 the preferential adoption of English was introduced, then it became
      the exclusive language from 2010. Later in 2008 there was the authoritative
      introduction of the magazine in the "informatics network" with the activation of
      a "web site" to constitute the parallel Digital Edition of Annali Italiani di
      Chirurgia, ISSN credited with the CNR, to constitute a large interactive library
      where there are nowadays collected in free reading all articles published in
      press from 2000 up to those published in the first half of 2015 - with subsequent
      to follow. In parallel it was inaugurated the section reserved to the individual
      "Clinical cases", published exclusively online in the same Digital Edition, with
      preservation of iconography colors. The own search motor of the "site"
      (www.annitalchir.com) enables the identification of all articles published in the
      Digital Edition, whether published in print or exclusively online, proceeding by
      title, by author, by keyword, and of course by date of publication. The
      functionality of the purchase mechanism of each article with the procedure of "e
      commerce" right from the site and the possibility for all readers to
      interactively express the own evaluation of published articles, has transformed
      the site into a "portal" constantly updated, and this has led to the growing
      number of foreign authors asking access with their papers to the magazine,
      especially from the Mediterranean area and Eastern Europe. Considering the
      variety and quality of the studies performed not only in Italy but also in such a
      vast geographical and cultural area, evident in the articles already published,
      it seems appropriate not only the substantial analysis by the Scientific
      Committee of the articles received to be published, but also to underline the
      care of the formal aspects of those proposed to the press, and to express a
      series of suggestions, to urge the Authors to improve the formal aspects in the
      preparation and exposure for their articles, to benefit of their image of Authors
      and for prestige of the magazine in an international perspective. This is the
      meaning of the Leading Article of this first issue 2016. I conclude by listing
      the qualitative preferences adopted for accepting articles to be published,
      provided that the individual clinical cases - the surgical "chronicle" - have a
      privileged place in the Digital Edition of Annali Italiani di Chirurgia,
      preserving the colors of the iconography, but that only exceptionally will be
      published in the printed issues. IDEAL TYPES OF PAPER to be submitted for
      publication in Annali Italiani di Chirurgia 1. Results of original research on a
      topical issue; 2. Update on a theme with contributions of personal experiences;
      3. Analysis of personal case histories of prospective studies; 4. Evaluation of
      case studies personal accompanied by extensive and comprehensive bibliographic
      revisions; 5. setups on the individual, with the formulation of opinions by the
      Authors; 6. Proposals for new surgical techniques; 7. Technological innovations;
      ACCEPTABLE TYPES OF PAPER to be submitted for publication in the Annals of
      Surgery Italian a) Editorial updating or development to the work of a single
      author; b) Description of unusual clinical cases (exclusively for online e
      publish in www.annitalchir.com); c) Reviews of multicenter studies. 

PMID- 27026139
TI  - Mitochondrial iron overload: causes and consequences.
AB  - Pathological overload of iron in the mitochondrial matrix has been observed in
      numerous diseases, including sideroblastic anemias, which have many causes, and
      in genetic diseases that affect iron-sulfur cluster biogenesis, heme synthesis,
      and mitochondrial protein translation and its products. Although high expression
      of the mitochondrial iron importer, mitoferrin, appears to be an underlying
      common feature, it is unclear what drives high mitoferrin expression and what
      other proteins are involved in trapping excess toxic iron in the mitochondrial
      matrix. Numerous examples of human diseases and model systems suggest that
      mitochondrial iron homeostasis is coordinated through transcriptional remodeling.
      A cytosolic/nuclear molecule may affect a transcriptional factor to coordinate
      the events that lead to iron accumulation, but no candidates for this role have
      yet been identified.

PMID- 27026140
TI  - University Students' Views on the Perceived Benefits and Drawbacks of Seeking
      Help for Mental Health Problems on the Internet: A Qualitative Study.
AB  - BACKGROUND: University students experience high levels of mental health problems
      yet very few seek professional help. Web-based mental health interventions may be
      useful for the university student population. However, there are few published
      qualitative studies that have examined the perceived benefits and drawbacks of
      seeking help for mental health problems on the Internet from the perspective of
      university students. OBJECTIVE: To investigate the attitudes of university
      students on mental health help-seeking on the Internet. METHODS: A total of 19
      university students aged 19-24 years participated in 1 of 4 focus groups to
      examine their views toward help-seeking for mental health problems on the
      Internet. RESULTS: Perceived concerns about Web-based help-seeking included
      privacy and confidentiality, difficulty communicating on the Internet, and the
      quality of Web-based resources. Potential benefits included anonymity/avoidance
      of stigma, and accessibility. Participants reported mixed views regarding the
      ability of people with similar mental health issues to interact on the Internet.
      CONCLUSIONS: These factors should be considered in the development of Web-based
      mental health resources to increase acceptability and engagement from university
      students.

PMID- 27026141
TI  - Long-term management of luminal urethral stricture in women.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to report our long-term experience
      of luminal urethral stricture (LUS) in women treated with dilation under general
      anesthesia. METHODS: Following institutional review board approval, charts of
      women who underwent urethral dilation (UD) under general anesthesia for LUS and
      had over 6 months' follow-up were reviewed. LUS was confirmed by urethroscopy. UD
      was performed using female dilators with guidewire and Heyman dilators when
      required. Outcome measures included the number of UD procedures and the duration
      and frequency of clean intermittent catheterization (CIC). Success was defined as
      the ability to void without repeat UD and with no need for CIC 1 year after UD.
      Possible predictive variables were analyzed. RESULTS: Between 2000 and 2013, a
      total of 30 out of the 32 women who underwent UD for LUS met the inclusion
      criteria. Mean follow-up was 59 (range: 7 to 151) months. Thirteen women in the
      success group showed improvement in the mean maximum flow rate (pre 11 ml/s to
      post 27.8 ml/s) and post-void residual (pre 85 ml to post 43 ml). In the failure
      group of 17 patients, 2 required chronic CIC 1 year after a single UD. Fifteen
      opted for repeat UD. After second (n = 5), third (n = 2), and fourth (n = 2) UD,
      9 patients came off CIC and reported durable satisfaction. Four women remained on
      regular CIC. Two required a permanent suprapubic catheter. CONCLUSION: At a mean
      follow-up of 5 years, UD for LUS produced durable resolution in 43 % of our
      patients. Another 30 % fully benefited from repeat UDs. Shorter duration of
      symptoms before presentation was significantly associated with success.

PMID- 27026142
TI  - The effect of surgical start time in patients undergoing minimally invasive
      sacrocolpopexy.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to determine if the surgical start
      time affects operating room time and the incidence of perioperative adverse
      events in patients undergoing minimally invasive sacrocolpopexy. METHODS: This is
      a retrospective cohort of 396 women who underwent laparoscopic and robotic
      sacrocolpopexy at a tertiary care center between January 2006 and December 2012.
      Cases were divided into those with a first, second or third start time. Operating
      room (OR) time was defined as time the patient entered the room to time out of
      the room (minutes) and the case time was defined as the period between incision
      and closure (minutes). Adverse events were defined a priori and also reported
      using the Clavien-Dindo grading scale. Logistic regression analysis was performed
      for categorical variables and multiple linear regression analysis for continuous
      variables. RESULTS: A total of 145 robotic and 261 conventional laparoscopic
      minimally invasive sacrocolpopexies were performed. Operating room time data were
      available for 396 cases. Of the cases, 63.9 % (253 out of 396) had a first start,
      32.1 % (127 out of 396) had a second start, and 4 % (16 out of 396) had a third
      start. Robotic and concomitant rectopexy cases were more likely to be performed
      as first-start cases and operating room time and case time were longest for first
      start cases. However, after adjusting for mode of surgery, concomitant
      procedures, previous surgeries, BMI, and age, this finding was no longer
      statistically significant. There was no difference in the rate of perioperative
      adverse events among first-, and second-/third-start cases. CONCLUSION: Surgical
      case start time does not appear to be associated with operating time or the
      incidence of perioperative adverse events in patients undergoing minimally
      invasive sacrocolpopexy.

PMID- 27026143
TI  - A philosophical approach to the concept of handedness: The phenomenology of lived
      experience in left- and right-handers.
AB  - This paper provides a philosophical evaluation of the concept of handedness
      prevalent but largely unspoken in the scientific literature. This literature
      defines handedness as the preference or ability to use one hand rather than the
      other across a range of common activities. Using the philosophical discipline of
      phenomenology, I articulate and critique this conceptualization of handedness.
      Phenomenology shows defining a concept of handedness by focusing on hand use
      leads to a right hand biased concept. I argue further that a phenomenological
      model based in spatial orientation rather than hand use provides a more inclusive
      concept of handedness.

PMID- 27026144
TI  - Aquagenic Palmoplantar Keratoderma as a CFTR-related Disorder.

PMID- 27026145
TI  - SMS text message reminders to improve infant vaccination coverage in Guatemala: A
      pilot randomized controlled trial.
AB  - BACKGROUND: Patient reminder systems are an evidence-based way to improve
      childhood vaccination rates but are difficult to implement in low- and middle
      income countries (LMICs). Short Message Service (SMS) texts may offer a potential
      low-cost solution, especially in LMICs where mobile phones are becoming more
      ubiquitous. OBJECTIVE: To determine if an SMS-based vaccination reminder system
      aimed at improving completion of the infant primary immunization series is
      feasible and acceptable in Guatemala. METHODS: A pilot randomized controlled
      trial was conducted at two public health clinics in Guatemala City. Infants aged
      8-14 weeks presenting for the first dose of the primary immunization series were
      enrolled in March-April 2013. Participants randomized into the intervention
      received three SMS reminders one week before the second and third dose. A follow
      up acceptability survey was administered to both groups. RESULTS: The
      participation rate was 86.8% (321/370); 8 did not own a cell phone and 12 could
      not use SMS. 96.9% of intervention parents were sent at least one SMS reminder
      prior to visit 2 and 96.3% prior to visit 3. Both intervention and usual care
      participants had high rates of vaccine and visit completion, with a non
      statistically significant higher percentage of children in the intervention
      completing both visit 2 (95.0% vs. 90.1%, p=.12) and visit 3 (84.4% vs. 80.7%,
      p=.69). More intervention vs. usual care parents agreed that SMS reminders would
      be helpful for remembering appointments (p<.0001), agreed to being interested in
      receiving future SMS reminders (p<.0001), and said that they would be willing to
      pay for future SMS reminders (p=.01). CONCLUSION: This proof of concept
      evaluation showed that a new application of SMS technology is feasible to
      implement in a LMIC with high user satisfaction. Larger studies with
      modifications in the SMS system are needed to determine effectiveness (Clinical
      Trial Registry NCT01663636).

PMID- 27026146
TI  - Status of vaccine research and development of vaccines for Chagas disease.

PMID- 27026147
TI  - Influenza vaccine effectiveness in preventing hospitalization among Beijing
      residents in China, 2013-15.
AB  - BACKGROUND: Estimates of influenza vaccination effectiveness (VE) are valuable
      for populations where the vaccine has been promoted in order to support
      vaccination policy and to permit evaluation of vaccination strategies. Such
      studies would be important for China due to limited data available during seasons
      when the vaccine strains matched or mismatched the circulating viruses. METHODS:
      We conducted a test-negative study in hospitals in Beijing. Patients admitted to
      five hospitals in the city were enrolled during the winter influenza seasons of
      2013-14 and 2014-15. Influenza virus infections were determined by PCR, and
      influenza vaccination records were extracted from a centralized electronic
      immunization registry. Influenza VE was estimated by logistic regression
      adjusting for age group, sex and chronic conditions, and matched by calendar
      week. RESULTS: A total of 2368 inpatients were recruited during the study period
      with a vaccination coverage in the control group of 12.8%. The overall estimate
      of influenza VE was 46.9% (95% CI: -20.4%, 76.6%) for the 2013-14 season and 5.0%
      (95% CI: -53.0%, 41.0%) for the 2014-15 season. Estimates of VE were relatively
      higher in children aged 6-17 years than older persons across two influenza
      seasons while estimates of VE for both adults and elderly were relatively low.
      CONCLUSIONS: Our findings were consistent with expected influenza vaccination
      effectiveness in seasons when the vaccine matched or mismatched circulating
      viruses. Strategies to increase influenza vaccine coverage could provide a public
      health benefit.

PMID- 27026149
TI  - Status of research and development of vaccines for chikungunya.
AB  - Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during the last
      decade has significantly expanded its geographical range and caused large
      outbreaks of human disease around the world. Although mortality rates associated
      with CHIKV outbreaks are low, acute and chronic illnesses caused by CHIKV
      represent a significant burden of disease largely affecting low and middle income
      countries. This report summarizes the current status of vaccine development for
      CHIKV.

PMID- 27026148
TI  - Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and
      tolerability profile in healthy, BCG-vaccinated, QuantiFERON((r))-TB Gold (+)
      Kenyan adults without evidence of tuberculosis.
AB  - In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35
      vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb)
      immunodominant antigens, in subjects with and without latent Mtb infection. HIV
      negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10
      QuantiFERON((r))-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized
      4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow
      up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1
      AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting
      severe AEs of injection site pain: 1 after the first vaccination and 1 after each
      vaccination, respectively. Two additional severe AEs considered vaccine-related
      were reported after the first vaccination in AERAS-402 QFT-G(+) subjects:
      elevated blood creatine phosphokinase and neutropenia, the latter slowly
      improving but remaining abnormal until study end. AERAS-402 was not detected in
      urine or throat cultures for any subject. In intracellular cytokine staining
      studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell
      responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with
      trends in the CD4+ T cells suggestive of boosting after the second vaccine dose,
      slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen
      TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from
      screening to end of study, seen in 50% of AERAS-402 recipients, were mostly
      minimal. This small study confirms acceptable safety and tolerability profiles
      for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include
      QFT-G(+) subjects.

PMID- 27026151
TI  - Author's reply.

PMID- 27026150
TI  - South Asia symposium on pneumococcal disease and the promise of vaccines -
      Meeting report.
AB  - Despite the licensure of the pneumococcal conjugate vaccine (PCV) in the US and
      other Western countries for over 14 years, as of September 2014 only 4 South
      Asian countries were using PCV in their universal immunization program. To
      generate momentum toward addressing this issue a "South Asia symposium on
      pneumococcal disease and the promise of vaccines" was organized just prior to the
      9th international symposium on pneumococci and pneumococcal diseases held in
      India recently. Leading scientists, program managers, and decision makers
      including ministry officials from the region participated in the meeting. The
      participants discussed available data on pneumococcal disease burden in South
      Asia, surveillance methods, efficacy and safety of pneumococcal conjugate
      vaccines (PCV), the status of PCV introduction, programmatic challenges in
      introducing PCV and available data on the impact of PCV in South Asia and
      globally. There was a strong consensus that available data on disease burden and
      the global experience with PCV justified the introduction PCV in all Asian
      countries in order to accelerate the gains in child survival in the region.

PMID- 27026152
TI  - Evaluating the risk factors of reintervention of neonates with PA/IVS and CPS/IVS
      after PBPV as initial intervention method.
AB  - OBJECTIVES: To analyze the clinical features, immediate and short-term outcome of
      percutaneous balloon pulmonary valvuloplasty (PBPV) of neonates with pulmonary
      atresia with intact ventricular septum (PA/IVS) or critical pulmonary stenosis
      with intact ventricular septum (CPS/IVS) who underwent PBPV as initial
      intervention methods to evaluate the risk factors of reintervention. METHOD:
      Thirty-eight neonates with PA/IVS or CPS/IVS admitted to Shanghai Xinhua Hospital
      between June 2009 and November 2014 who underwent PBPV as initial procedures were
      respectively studied. We analyzed their clinical features, the immediate and
      short-term outcome of PBPV, and evaluated the risk factors for reintervention.
      RESULTS: Thirty-eight neonates with PA/IVS and CPS/IVS who underwent PBPV as
      initial procedures were included in our study with a mean age of 13+/-8 days.
      Among the 12 patients who underwent reintervention, 7 patients had PA/IVS (64%)
      and 5 had CPS/IVS (36%). Patients with PA/IVS (p=0.005), small pulmonary valve
      diameter (p=0.035), and bad pulmonary valve development were important risk
      factors. The immediate and short-term outcome of PBPV was better in patients who
      did not need reintervention, and the peak-to-peak pulmonary transvalvular
      gradient in the 1st month after PBPV had the best capability in predicting
      reintervention with help of receiver operating characteristic curve and the
      logistic regression analysis. Days of prostaglandin E1 (PGE1) infusion after PBPV
      >5 days was also found to be a risk factor for reintervention. CONCLUSION: The
      short- and mid-term outcome of pulmonary valve perforation and PBPV in neonates
      with PA/IVS and CPS/IVS was favorable. Risk factors include PA/IVS, small
      pulmonary valve, bad short-term pulmonary valve development, the peak-to-peak
      pulmonary transvalvular gradient in the 1st month after procedure >42mmHg, and
      PGE1 infusion >5 days.

PMID- 27026153
TI  - Novel pyrimidine based semicarbazones: Confirmation of four binding site
      pharmacophoric model hypothesis for antiepileptic activity.
AB  - BACKGROUND: Epilepsy is a neurological disorder, characterized by seizures
      accompanied by loss or disturbance of consciousness affecting various physical
      and mental functions. Current anticonvulsant drugs are effective in controlling
      seizures in about 70% of cases, but their use is often limited by side effects
      like ataxia, megaloblastic anemia, hepatic failure. In search for a novel
      anticovulsant drug with better efficacy and lower toxicity, a series of novel
      pyrimidine based semicarbazone were designed and evaluated for antiepileptic
      activity. METHODS: The test compounds were designed on the basis of four site
      binding hypothesis proposed for anticonvulsant activity. The chemical structures
      of the test compounds were elucidated using spectral (IR, 1H NMR, 13C NMR and MS)
      and elemental analysis. The minimal motor impairment activity was determined in
      mice using rotorod test. The maximal electroshock seizure (MES) and subcutaneous
      pentylenetrtrazole (scPTZ) models were employed for anticonvulsant evaluation.
      RESULTS: The results reveal that 76% of the compounds were active in the MES
      screening as compared to 53% of the compounds in the scPTZ test. Test compounds
      showed some MES selectivity displaying their effectiveness in generalized
      seizures of the tonic-clonic type. The molecular docking analysis of
      semicarbazone derivatives showed good ligand-receptor interactions with specially
      hydrogen bond interactions with ARG192, GLU270 and THR353 amino acid of receptor.
      CONCLUSION: The present report confirms that pharmacophore model with four
      binding sites is crucial for anticonvulsant activity in the semicarbazones.

PMID- 27026154
TI  - Pain at the back of the heel.

PMID- 27026155
TI  - The cell-wall active mannuronan C5-epimerases in the model brown alga Ectocarpus:
      From gene context to recombinant protein.
AB  - Mannuronan C5-epimerases (ManC5-Es) catalyze in brown algae the remodeling of
      alginate, a major cell-wall component which is involved in many biological
      functions in these organisms. ManC5-Es are present as large multigenic families
      in brown algae, likely indicating functional specificities and specializations.
      ManC5-Es control the distribution pattern of (1-4) linked beta-d-mannuronic acid
      (M) and alpha-l-guluronic acid (G) residues in alginates, giving rise to widely
      different polysaccharide compositions and sequences, depending on tissue, season,
      age, or algal species. As such they are also a source of powerful new tools for
      the biotechnological and enzymatic processing of alginates, to match the growing
      interest for food hydrocolloids and in biomedical and nanotechnological
      applications. We report here the first heterologous production of a ManC5-E of
      brown algal origin that is successfully refolded in an active form. The activity
      was measured by 1H NMR and by an indirect enzymatic assay using a known bacterial
      alginate lyase. The transcript expression as a function of the developmental
      program of the brown alga Ectocarpus, together with the bioinformatic analyses of
      the corresponding gene context of this multigenic family, is also presented.

PMID- 27026156
TI  - An Evaluation of Light-Emitting Diode (LED) Traps at Capturing Phlebotomine Sand
      Flies (Diptera: Psychodidae) in a Livestock Area in Brazil.
AB  - A study to evaluate the use of light-emitting diodes (LEDs) as an attractant for
      phlebotomine sand flies at two animal pens in a livestock area in Brazil was
      performed. Light-suction traps were operated overnight with the following light
      sources: green, blue, and incandescent (control) lights. In total, 22 individual
      collections were made at each site and 44 with each trap type. In total, 2,542
      specimens belonging to 14 phlebotomine species were collected. The most abundant
      species in the light traps were Nyssomyia whitmani, Evandromyia evandroi,
      Micropygomyia goiana, Lutzomyia longipalpis, and Bichromomyia flaviscutellata
      Taking the two sites together, the green-LED light was the most attractive,
      followed by the blue and incandescent lights, and the difference between the
      green-LED and the control was statistically significant. Most species were green
      biased at both sites, but some species-specific differences were observed.
      However, even with these differences, the standard incandescent light was
      outcompeted by LEDs. The green-LED-biased response observed in the present study,
      together with numerous advantages in favor of LEDs, suggests that the green-LED
      light source can be used as an effective substitute for the currently used
      incandescent bulb in monitoring traps for phlebotomine sand flies in Brazil.

PMID- 27026157
TI  - The Interactive Role of Immature Stage Competition, Cohort Overlap, and Resource
      Limitation on the Population Viability of the Treehole Mosquito Aedes triseriatus
      (Diptera: Culicidae).
AB  - The size and success of epidemiologically significant adult mosquito populations
      are inherently tied to the conditions of the aquatic habitat in which juvenile
      stages grow until eclosion. While resource competition and quality are well
      established controls to juvenile growth and survival, the implications to overall
      population rates of increase are less understood due to the large sample sizes
      needed to parameterize population models for all five juvenile life stages under
      multiple environmental and demographic conditions. Here, we present the results
      of >4,300 trials of wild-caught Aedes triseriatus (Say, 1823) larvae and pupae
      reared under varying resource quantity crossed by the presence or absence of
      competition within a single cohort as well as multiple overlapping cohorts.
      Demographic projection was used to make predictions of the realized growth rates
      of simulated Ae. triseriatus populations across the range of potential Ae.
      triseriatus fecundity. Further, to inform control efforts on juvenile habitat, we
      constructed a stochastic simulation to estimate the rates of successful emergence
      from habitats under different resource regimes and levels of cohort overlap. We
      found that while Ae. triseriatus populations were robust to low resource levels
      and competition within a cohort, the combination of these stressors with multiple
      cohort overlap led to self-limitation or complete collapse of mosquito
      populations. Despite this importance of intraspecific competition to population
      viability, the stochastic simulation revealed only a modest self-limitation of
      adult emergence, with the clear implication that high-resource habitats are a
      higher value control target.

PMID- 27026158
TI  - Heterogeneity of Mosquito (Diptera: Culicidae) Control Community Size, Research
      Productivity, and Arboviral Diseases Across the United States.
AB  - Multiple factors lead to extensive variation in mosquito and mosquito-borne virus
      control programs throughout the United States. This variation is related to
      differences in budgets, number of personnel, operational activities targeting
      nuisance or vector species, integration of Geographical Information Systems, and
      the degree of research and development to improve management interventions
      through collaboration with academic institutions. To highlight this
      heterogeneity, the current study evaluates associations among the size of a
      mosquito control community, the research productivity, and the mosquito-borne
      virus human disease burden among states within the continental United States. I
      used the attendance at state mosquito and vector control meetings as a proxy for
      the size of the mosquito control community in each state. To judge research
      productivity, I used all peer-reviewed publications on mosquitoes and mosquito
      borne viruses using data originating in each state over a 5- and 20-yr period.
      Total neuroinvasive human disease cases caused by mosquito-borne viruses were
      aggregated for each state. These data were compared directly and after adjusting
      for differences in human population size for each state. Results revealed that
      mean meeting attendance was positively correlated with the number of publications
      in each state, but not after correcting for the size of the population in each
      state. Additionally, human disease cases were positively correlated with the
      number of publications in each state. Finally, mean meeting attendance and human
      disease cases were only marginally positively associated, and no correlation
      existed after correcting for human population size. These analyses indicated that
      the mosquito control community size, research productivity, and mosquito-borne
      viral human disease burden varied greatly among states. The mechanisms resulting
      in this variation were discussed and the consequences of this variation are
      important given the constantly changing environment due to invasive mosquito
      species and arboviruses, urbanization, immigration, global travel, and climate
      change.

PMID- 27026159
TI  - Effects of Temperature and Tissue Type on the Development of Megaselia scalaris
      (Diptera: Phoridae).
AB  - The scuttle fly, Megaselia scalaris (Loew) (Diptera: Phoridae), is of medical,
      veterinary, and forensic importance. In the case of the latter, M. scalaris is
      commonly associated with indoor death or neglect cases of humans or household
      animals, and its larvae are useful in determining time of colonization (TOC).
      This study is the first to examine the effects of different temperatures and
      tissues from two vertebrate species on the growth rate and larval length of M.
      scalaris A preliminary validation of these data was also conducted. Immatures of
      M. scalaris were reared on either bovine or porcine biceps femoris at 24  
      degrees C, 28  degrees C, and 32  degrees C. Temperature significantly impacted
      immature development time, including egg eclosion, eclosion to pupation, and
      pupation to adult emergence, to favor faster development at higher temperatures.
      From ovipostion to eclosion, development rate was 32.1% faster from 24  degrees C
      to 28  degrees C, 13.9% faster from 28  degrees C to 32  degrees C, and 45.5%
      faster from 24  degrees C to 32  degrees C. Development from eclosion to pupation
      displayed similar results with differences of 30.3% between 24  degrees C and 28 
      degrees C, 15.4% between 28  degrees C and 32  degrees C, and 45.2% between 24 
      degrees C and 32  degrees C. Development from pupation to adult emergence,
      likewise, displayed a 44.4% difference from 24  degrees C and 28  degrees C, 7.3%
      from 28  degrees C to 32  degrees C, and 51.2% from 24  degrees C to 32  degrees
      C. From oviposition to adult emergence, M. scalaris needed ~32.7% more hours to
      complete development when reared at 24  degrees C than 28  degrees C, 8.5% when
      reared at 28  degrees C rather than 32  degrees C, and 38.4% more time when
      reared at 24  degrees C over 32  degrees C. Tissue type did not significantly
      impact development.A preliminary validation study was conducted in four indoor
      environments (two attics, a closet, and a bathroom) spanning two different
      buildings. Utilizing minimum and mean lengths, time of colonization estimates
      were underestimated in all instances. The predicted range encompassed the actual
      TOC for two of the four environments. On average, when using minimum length, time
      of colonization was underestimated by 45%, but overestimated by only 2% when
      using maximum development range. Data generated from this research could be
      useful when estimating a TOC of decomposing vertebrate remains. Future research
      will need to examine development for each stadium in order to increase precision
      of such estimates.

PMID- 27026160
TI  - The Impact of Cycling Temperature on the Transmission of West Nile Virus.
AB  - West Nile virus (WNV) is an important cause of disease in humans and animals.
      Risk of WNV infection varies seasonally, with the greatest risk during the
      warmest parts of the year due in part to the accelerated extrinsic incubation
      rate of the virus in mosquitoes. Rates of extrinsic incubation have been shown in
      constant-temperature studies to increase as an approximately linear function of
      temperature, but for other vector-borne pathogens, such as malaria or dengue
      virus, nonlinear relationships have been demonstrated under cycling temperatures
      near the thermal limits of pathogen replication. Using typical daily air
      temperature profiles from three key periods of WNV amplification in a
      hyperendemic area of WNV activity in California's Central Valley, as well as a
      fourth temperature profile based on exposures that would result from daily
      mosquito host-seeking and resting behavior, we explored the impacts of cycling
      temperatures on WNV transmission by Culex tarsalis Coquillett, one of the
      principal vectors in the western United States. The daily cycling temperature
      ranges studied were representative of those that occur across much of California,
      but they did not significantly alter the extrinsic incubation period of WNV
      compared with estimates from mean temperatures alone. This suggests that within
      the relatively broad range we studied, WNV incubation rates are a simple function
      of mean temperature. Realistic daily temperature patterns that reflected
      mosquitoes' avoidance of daytime high temperatures during summer reduced
      transmission over time compared with air temperatures, indicating that adjustment
      for mosquito exposure temperatures would be prudent for calculating risk.

PMID- 27026161
TI  - Habitat Suitability Model for the Distribution of Ixodes scapularis (Acari:
      Ixodidae) in Minnesota.
AB  - Ixodes scapularis Say, the black-legged tick, is the primary vector in the
      eastern United States of several pathogens causing human diseases including Lyme
      disease, anaplasmosis, and babesiosis. Over the past two decades, I. scapularis
      borne diseases have increased in incidence as well as geographic distribution.
      Lyme disease exists in two major foci in the United States, one encompassing
      northeastern states and the other in the Upper Midwest. Minnesota represents a
      state with an appreciable increase in counties reporting I. scapularis-borne
      illnesses, suggesting geographic expansion of vector populations in recent years.
      Recent tick distribution records support this assumption. Here, we used those
      records to create a fine resolution, subcounty-level distribution model for I.
      scapularis using variable response curves in addition to tests of variable
      importance. The model identified 19% of Minnesota as potentially suitable for
      establishment of the tick and indicated with high accuracy (AUC = 0.863) that the
      distribution is driven by land cover type, summer precipitation, maximum summer
      temperatures, and annual temperature variation. We provide updated records of
      established populations near the northwestern species range limit and present a
      model that increases our understanding of the potential distribution of I.
      scapularis in Minnesota.

PMID- 27026162
TI  - Spatiotemporal Co-occurrence of Flanders and West Nile Viruses Within Culex
      Populations in Shelby County, Tennessee.
AB  - West Nile virus (WNV) and Flanders virus (FLAV) can cocirculate in Culex
      mosquitoes in parts of North America. A large dataset of mosquito pools tested
      for WNV and FLAV was queried to understand the spatiotemporal relationship
      between these two viruses in Shelby County, TN. We found strong evidence of
      global clustering (i.e., spatial autocorrelation) and overlapping of local
      clustering (i.e., Hot Spots based on Getis Ord Gi*) of maximum likelihood
      estimates (MLE) of infection rates (IR) during 2008-2013. Temporally, FLAV
      emerges and peaks on average 10.2 wk prior to WNV based on IR. Higher levels of
      WNV IR were detected within 3,000 m of FLAV-positive pool buffers than outside
      these buffers.

PMID- 27026163
TI  - Dengue Virus-1 Infection Did Not Alter the Behavioral Response of Aedes aegypti
      (Diptera: Culicidae) to DEET.
AB  - No licensed vaccine or antiviral drug against dengue virus (DENV) is available;
      therefore, most of the effort to prevent this disease is focused on reducing
      vector-host interactions. One of the most widely accepted methods of blocking
      vector-human contact is to use insect repellents to interfere with mosquito host
      seeking behavior. Some arboviruses can replicate in the nervous system of the
      vector, raising the concern that arboviral infection may alter the insect
      behavioral response toward chemical stimuli. Three different Aedes aegypti (L.)
      mosquito cohorts: DENV-1-injected, diluent-injected, and uninjected were
      subjected to behavioral tests using a high-throughput screening system with 2.5%
      DEET and 0.14% DEET on 1, 4, 7, 10, 14, and 17 d postinjection. All test cohorts
      exhibited significant contact irritant or escape responses when they were exposed
      to 2.5% or 0.14% DEET. However, we found no biologically relevant irritancy
      response change in DENV-1-infected Ae. aegypti mosquitoes when they were exposed
      to DEET. Further studies evaluating the effects of other arboviral infections on
      insect repellents activity are necessary in order to provide better
      recommendation on the prevention of vector-borne disease transmission.

PMID- 27026164
TI  - Development of a tool to measure women's perception of respectful maternity care
      in public health facilities.
AB  - BACKGROUND: Maternal mortality continues to be the biggest challenge facing
      Ethiopia and other developing countries. Although progress has been made in
      making maternity services available closer to the community, the rate of
      deliveries attended by skilled birth attendants has remained very low. Absence of
      respectful maternity care (RMC) is believed to have contributed to low
      utilization of facility delivery services. This study outlines steps undertaken
      to construct and validate a scale that measures women's perception of respectful
      maternity care provided in health facilities. METHODS: An inductive item
      generation process that included a literature review and in-depth interviews with
      labor and delivery clients, followed by an expert review, assured face validity
      and content validity of the tool. A draft RMC scale with 37 items and two
      additional measures of global satisfaction items, measured on a five-point Likert
      scale, were administered to a developmental sample of 509 postnatal care clients
      visiting facilities immediately after childbirth to 7 weeks postpartum. IBM SPSS
      20 was used to perform exploratory factor analysis (EFA) using principal
      component analysis (PCA) with oblique rotation method. RESULTS: The final RMC
      scale with 15 items was loaded on four components. The extracted components were
      labeled as friendly care, abuse-free care, timely care, and discrimination-free
      care. The final RMC scale correlated strongly with the global satisfaction
      measures, indicating criterion-related validity of the scale. Content-related
      validity was assured by the process of item generation. Construct validity of the
      RMC scale was confirmed by high average factor loading of the four components
      ranging from 0.76 to 0.82 and low correlation between the components. Stability
      of the scale was confirmed by running PCA in a randomly selected split sample of
      320 samples from the validation sample. The final 15-item scale showed an
      adequate reliability with alpha = 0.845. CONCLUSION: The 15-item RMC scale is a
      valid and reliable measure of women's perception of RMC received in health
      facilities. We recommend that health facilities use the RMC scale in urban public
      health facilities and that other researchers conduct further exploratory and
      confirmatory factor analysis in different geographic areas.

PMID- 27026165
TI  - Spider silk-like proteins derived from transgenic Nicotiana tabacum.
AB  - The high tensile strength and biocompatibility of spider dragline silk makes it a
      desirable material in many engineering and tissue regeneration applications.
      Here, we present the feasibility to produce recombinant proteins in transgenic
      tobacco Nicotiana tabacum with sequences representing spider silk protein
      building blocks . Recombinant mini-spidroins contain native N- and C-terminal
      domains of major ampullate spidroin 1 (rMaSp1) or rMaSp2 flanking an abbreviated
      number (8, 16 or 32) of consensus repeat domains. Two different expression
      plasmid vectors were tested and a downstream chitin binding domain and self
      cleavable intein were included to facilitate protein purification. We confirmed
      gene insertion and RNA transcription by PCR and reverse-transcriptase PCR,
      respectively. Mini-spidroin production was detected by N-terminus specific
      antibodies. Purification of mini-spidroins was performed through chitin affinity
      chromatography and subsequent intein activation with reducing reagent. Mini
      spidroins, when dialyzed and freeze-dried, formed viscous gelatin-like fluids.

PMID- 27026166
TI  - Exploring the experiences and implementing strategies for physiotherapy students
      who perceive they have been bullied or harassed on clinical placements:
      participatory action research.
AB  - OBJECTIVES: To explore and empower physiotherapy students who reported being
      bullied or harassed on clinical placements by co-developing, implementing and
      evaluating strategies that could be adopted by the university. DESIGN: A
      participatory action research design was employed. PARTICIPANTS: Two focus groups
      were carried out involving 5 final year physiotherapy students. In the first
      focus group negative experiences were discussed and coping strategies suggested
      for their penultimate placement. A second focus group was held following the
      students' final placement when these strategies were evaluated and further ones
      proposed. ANALYSIS: A thematic analysis of the data was carried out. RESULTS:
      Four themes and sub-themes emerged from the analysis. The four themes were
      negative experiences on placement, coping strategies, the role of the visiting
      tutor and the assessment. The students' highlighted various degrees of threat to
      their efficacy and in most cases could draw upon a suggested 'tool box' of coping
      strategies. They all agreed that serious cases of harassment require wider
      support from the University senior management team which should be clearly
      documented. The role of the visiting tutor was deemed to be critical in these
      situations and recommendations were made regarding this role and the assessment
      of placements. CONCLUSION: Students understand that they are going to be assessed
      before achieving their professional qualification and in essence they will always
      find themselves in a hierarchical position but equally fairness must prevail and
      it is important and that there are clear avenues for them to seek support.

PMID- 27026167
TI  - Respiratory training improved ventilatory function and respiratory muscle
      strength in patients with multiple sclerosis and lateral amyotrophic sclerosis:
      systematic review and meta-analysis.
AB  - BACKGROUND: Among neurodegenerative diseases, multiple sclerosis (MS) and
      amyotrophic lateral sclerosis (ALS) have a high rate of respiratory disability.
      OBJECTIVES: To analyze the effects of respiratory muscle training (RMT) on
      ventilatory function, muscle strength and functional capacity in patients with MS
      or ALS. DATA SOURCES: A systematic review and meta-analysis of randomized
      controlled trials (RCTs) was performed. The sources were MEDLINE, PEDro, Cochrane
      CENTRAL, EMBASE, and LILACS, from inception to January 2015. STUDY
      SELECTION/ELIGIBILITY CRITERIA: The following were included: RCTs of patients
      with neurodegenerative diseases (MS or lateral ALS) who used the intervention as
      RMT (inspiratory/expiratory), comparison with controls who had not received RMT
      full time or were receiving training without load, and evaluations of ventilatory
      function (forced vital capacity - FVC, forced expiratory volume in one second -
      FEV1, maximum voluntary ventilation - MVV), respiratory muscle strength (maximal
      expiratory pressure/maximum inspiratory pressure - MEP/MIP) and functional
      capacity (6-minute walk test - 6MWT). RESULTS: The review included nine papers,
      and a total of 194 patients. It was observed that RMT significantly increased at
      MIP (23.50cmH2O; 95% CI: 7.82 to 39.19), MEP (12.03cmH2O; 95% CI: 5.50 to 18.57)
      and FEV1 (0.27L; 95% CI: 0.12 to 0.42) compared to the control group, but did not
      differ in FVC (0.48L; 95% CI: -0.15 to 1.10) and distance in 6MWT (17.95m; 95%
      CI: -4.54 to 40.44). CONCLUSION: RMT can be an adjunctive therapy in the
      rehabilitation of neurodegenerative diseases improving ventilatory function and
      respiratory strength.

PMID- 27026168
TI  - Validating Non-invasive EEG Source Imaging Using Optimal Electrode Configurations
      on a Representative Rat Head Model.
AB  - The curtain of technical limitations impeding rat multichannel non-invasive
      electroencephalography (EEG) has risen. Given the importance of this preclinical
      model, development and validation of EEG source imaging (ESI) is essential. We
      investigate the validity of well-known human ESI methodologies in rats which
      individual tissue geometries have been approximated by those extracted from an
      MRI template, leading also to imprecision in electrode localizations. With the
      half and fifth sensitivity volumes we determine both the theoretical minimum
      electrode separation for non-redundant scalp EEG measurements and the electrode
      sensitivity resolution, which vary over the scalp because of the head geometry.
      According to our results, electrodes should be at least ~3 to 3.5 mm apart for an
      optimal configuration. The sensitivity resolution is generally worse for
      electrodes at the boundaries of the scalp measured region, though, by analogy
      with human montages, concentrates the sensitivity enough to localize sources.
      Cramer-Rao lower bounds of source localization errors indicate it is
      theoretically possible to achieve ESI accuracy at the level of anatomical
      structures, such as the stimulus-specific somatosensory areas, using the
      template. More validation for this approximation is provided through the
      comparison between the template and the individual lead field matrices, for
      several rats. Finally, using well-accepted inverse methods, we demonstrate that
      somatosensory ESI is not only expected but also allows exploring unknown
      phenomena related to global sensory integration. Inheriting the advantages and
      pitfalls of human ESI, rat ESI will boost the understanding of brain
      pathophysiological mechanisms and the evaluation of ESI methodologies, new
      pharmacological treatments and ESI-based biomarkers.

PMID- 27026169
TI  - A Clinical Approach to a Child with Hypoalbuminemia and Lymphopenia.

PMID- 27026171
TI  - Kono-type anastomosis in a patient with severe multi-recurrent Crohn's disease.

PMID- 27026170
TI  - Novel Mutations Causing C5 Deficiency in Three North-African Families.
AB  - The complement system plays a central role in defense to encapsulated bacteria
      through opsonization and membrane attack complex (MAC) dependent lysis. The three
      activation pathways (classical, lectin, and alternative) converge in the cleavage
      of C5, which initiates MAC formation and target lysis. C5 deficiency is
      associated to recurrent infections by Neisseria spp. In the present study,
      complement deficiency was suspected in three families of North-African origin
      after one episode of invasive meningitis due to a non-groupable and two uncommon
      Meningococcal serotypes (E29, Y). Activity of alternative and classical pathways
      of complement were markedly reduced and the measurement of terminal complement
      components revealed total C5 absence. C5 gene analysis revealed two novel
      mutations as causative of the deficiency: Family A propositus carried a
      homozygous deletion of two adenines in the exon 21 of C5 gene, resulting in a
      frameshift and a truncated protein (c.2607_2608del/p.Ser870ProfsX3 mutation).
      Families B and C probands carried the same homozygous deletion of three
      consecutive nucleotides (CAA) in exon 9 of the C5 gene, leading to the deletion
      of asparagine 320 (c.960_962del/p.Asn320del mutation). Family studies confirmed
      an autosomal recessive inheritance pattern. Although sharing the same
      geographical origin, families B and C were unrelated. This prompted us to
      investigate this mutation prevalence in a cohort of 768 North-African healthy
      individuals. We identified one heterozygous carrier of the p.Asn320del mutation
      (allelic frequency = 0.065 %), indicating that this mutation is present at low
      frequency in North-African population.

PMID- 27026172
TI  - Respiratory Collapse of the Inferior Vena Cava Reflects Volume Shift and
      Subsequent Fluid Refill in Acute Heart Failure Syndrome.
AB  - BACKGROUND: Fluid redistribution rather than fluid accumulation plays an
      important role in the development of acute heart failure (HF) syndrome. Patients
      with fluid redistribution develop acute HF without prominent volume overload. We
      investigated volume status by measuring the diameter of the inferior vena cava
      (IVC) and examining variations in hemoglobin and hematocrit. METHODS AND RESULTS:
      Seventy-four consecutive patients admitted for acute HF syndrome were analyzed.
      Blood tests and measurement of IVC diameter after stabilization of respiratory
      distress were performed on admission and were repeated after 24 h. IVC
      collapsibility index (IVC-CI) was calculated as (maximum IVC-minimum IVC)/maximum
      IVC. According to the initial IVC-CI, the patients were divided into the collapse
      group (IVC-CI >=0.5: n=34) and the non-collapse group (IVC-CI <0.5: n=40).
      Initial blood pressure was higher in the collapse group (P<0.001). Although 24-h
      urine volume did not differ between the groups, hemoglobin (P<0.001) and
      hematocrit (P<0.001) decreased significantly in the collapse group but not in the
      non-collapse group after 24 h. Furthermore, IVC-CI significantly decreased in the
      collapse group after 24 h (P=0.003). CONCLUSIONS: In acute HF syndrome, IVC-CI
      >=0.5 on admission suggests a volume shift from the central vein into the
      pulmonary vasculature. Fluid refill occurs within 24 h after admission. This
      observation could be helpful in selecting strategies for diuretic use. (Circ J
      2016; 80: 1171-1177).

PMID- 27026173
TI  - Exhaled Acetone Concentration Is Related to Hemodynamic Severity in Patients With
      Non-Ischemic Chronic Heart Failure.
AB  - BACKGROUND: We hypothesized that exhaled acetone concentration (EAC), reflecting
      altered blood ketone body metabolism and increased acetone exhaust because of
      pulmonary congestion in heart failure (HF), would correlate with hemodynamic
      parameters in patients with non-ischemic chronic HF. METHODS AND RESULTS: We
      prospectively enrolled 102 non-ischemic HF patients with New York Heart
      Association (NYHA) class I-III. Exhaled breath was collected after an overnight
      fast. Echocardiography and cardiac catheterization were performed in all
      patients. We also enrolled 17 control patients without HF. EAC in the HF patients
      was significantly higher than that in the control patients (median EAC; 0.53 vs.
      0.38 ppm, P=0.012). EAC positively correlated with blood total ketone bodies
      (r=0.454, P<0.001), NYHA class (r=0.489, P<0.001), and plasma B-type natriuretic
      peptide (r=0.316, P=0.001). Right heart catheterization revealed that EAC
      significantly correlated with pulmonary capillary wedge pressure (PCWP, r=0.377,
      P<0.001). Receiver-operating characteristic analysis revealed that EAC >1.05 ppm
      was associated with PCWP >=18 mmHg (area under the curve [AUC] 0.726, sensitivity
      50%, specificity 89%). EAC was shown to be a comparable diagnostic biomarker for
      HF to BNP (AUC 0.760, sensitivity 80%, specificity 70%). CONCLUSIONS: EAC may be
      a novel noninvasive biomarker that correlates hemodynamic severity in non
      ischemic chronic HF. (Circ J 2016; 80: 1178-1186).

PMID- 27026174
TI  - Anti-alpha-enolase antibodies in membranous nephropathy: isotype matters.

PMID- 27026175
TI  - Magnesium ions increase the activity of Bacillus deramificans pullulanase
      expressed by Brevibacillus choshinensis.
AB  - Addition of MgCl2 to the culture medium has been found to dramatically increase
      the activity of Bacillus deramificans pullulanase expressed by Brevibacillus
      choshinensis. The specific activity of the pullulanase obtained from medium
      supplemented with MgCl2 was also higher than that obtained in culture medium
      without added magnesium ions. In this work, the mechanism of this increase was
      studied. When cultured in medium without added magnesium ions, B. choshinensis
      mainly produced a thermolabile, inactive form of pullulanase. The addition of
      magnesium ions led to the production of a thermostable, active form of
      pullulanase. Circular dichroism assays revealed considerable differences in
      secondary structure between the active and inactive pullulanase forms.
      Transmission electron microscopy suggested that magnesium ion addition inhibits
      the shedding of cell wall protein (HWP) layers from the cell surface.
      Quantitative real-time PCR showed that magnesium ion addition represses
      transcription of HWP. Because the pullulanase gene and HWP have identical
      promoters, pullulanase gene transcription was also inhibited. These results
      suggest that when pullulanase is expressed slowly, it tends to fold into an
      active form. 

PMID- 27026176
TI  - Changes in microbial community structures due to varying operational conditions
      in the anaerobic digestion of oxytetracycline-medicated cow manure.
AB  - Management of manure containing veterinary antibiotics is a major concern in
      anaerobic treatment systems because of their possible adverse effects on
      microbial communities. Therefore, the aim of study was to investigate how
      oxytetracycline (OTC) influences bacteria and acetoclastic and hydrogenotrophic
      methanogens under varying operational conditions in OTC-medicated and non
      medicated anaerobic cow manure digesters. Concentrations of OTC and its
      metabolites throughout the anaerobic digestion were determined using ultraviolet
      high-performance liquid chromatography (UV-HPLC) and tandem liquid chromatography
      mass spectrometry (LC/MS/MS), respectively. Fluorescent in situ hybridization,
      denaturing gradient gel electrophoresis, cloning, and sequencing analyses were
      used to monitor changes in microbial community structures. According to the
      results of analytical and molecular approaches, operating conditions highly
      influence active microbial community dynamics and associate with biogas
      production and elimination of OTC and its metabolites during anaerobic digestion
      of cow manure in the presence of an average initial concentration of 2.2 mg
      OTC/L. The impact of operating conditions has a drastic effect on acetoclastic
      methanogens than hydrogenotrophic methanogens and bacteria. 

PMID- 27026177
TI  - Organization and function of anionic phospholipids in bacteria.
AB  - In addition to playing a central role as a permeability barrier for controlling
      the diffusion of molecules and ions in and out of bacterial cells, phospholipid
      (PL) membranes regulate the spatial and temporal position and function of
      membrane proteins that play an essential role in a variety of cellular functions.
      Based on the very large number of membrane-associated proteins encoded in
      genomes, an understanding of the role of PLs may be central to understanding
      bacterial cell biology. This area of microbiology has received considerable
      attention over the past two decades, and the local enrichment of anionic PLs has
      emerged as a candidate mechanism for biomolecular organization in bacterial
      cells. In this review, we summarize the current understanding of anionic PLs in
      bacteria, including their biosynthesis, subcellular localization, and
      physiological relevance, discuss evidence and mechanisms for enriching anionic
      PLs in membranes, and conclude with an assessment of future directions for this
      area of bacterial biochemistry, biophysics, and cell biology. 

PMID- 27026178
TI  - Experimental evaluation of the metabolic reversibility of ANME-2d between
      anaerobic methane oxidation and methanogenesis.
AB  - The "reverse methanogenesis" hypothesis as the metabolic pathway of AOM has
      recently been supported in the novel ANME lineage ANME-2d in denitrifying
      anaerobic methane oxidation (DAMO). However, no previous studies have
      experimentally evaluated the reversal of methane oxidation and methane production
      in this archaea. In the present study, the metabolic reversibility of ANME-2d
      from AOM to methanogenesis was evaluated using H2/CO2 and acetate as substrates.
      The results showed that the system produced methane from H2/CO2 but not from
      acetate. However, the clone library and real-time PCR analysis of the culture
      showed that both the percentage and quantity of ANME-2d decreased significantly
      under this condition, while methanogen abundance increased. Further high
      throughput sequencing results showed that the archaea community did not change at
      the fourth day after H2/CO2 was supplied, but changed profoundly after
      methanogenesis took place for 3 days. The percentage of DAMO archaea in the total
      archaea decreased obviously, while more methanogens grew up during this period.
      Comparatively, the bacteria community changed profoundly at the fourth day. These
      results indicated that ANME-2d might not reverse its metabolism to produce
      methane from H2/CO2 or acetate. After archaea were returned to DAMO conditions,
      DAMO activity decreased and the amount of ANME-2d continued to fall, implying
      that the lineage had suffered from severe injury and required a long recovery
      time. 

PMID- 27026179
TI  - Synthesis of Tetrahydronaphthyridines from Aldehydes and HARP Reagents via
      Radical Pictet-Spengler Reactions.
AB  - The combination of aldehydes with newly designed HARP (halogen amine radical
      protocol) reagents gives access to alpha-substituted tetrahydronaphthyridines. By
      using different HARP reagents, various regioisomeric structures can be prepared
      in a single operation. These products, which are of high value in medicinal
      chemistry, are formed in a predictable manner via a formal Pictet-Spengler
      reaction of electron-poor pyridines that would not participate in the
      corresponding polar reactions. 

PMID- 27026180
TI  - Cognitive Testing of an Electronic Version of the Faces Pain Scale-Revised with
      Pediatric and Adolescent Sickle Cell Patients.
AB  - BACKGROUND: Patient diaries and pain scales can capture the course and
      complications of pain managed at home in children. The Faces Pain Scale-Revised
      (FPS-R) is a validated scale showing reliability in children, but it has not been
      validated in children with sickle cell disease (SCD). OBJECTIVE: The purpose of
      this study was to evaluate comprehension and usability of an electronic modified
      version of the FPS-R among pediatric patients with SCD. METHODS: This was a cross
      sectional, qualitative study involving in-person interviews with
      children/adolescents from the USA and their parents/legal guardians. Interviews
      involved cognitive debriefing and usability testing of the FPS-R. RESULTS: In
      total, 22 children with SCD aged 4-17 years participated. Children aged 4-6 were
      generally unable to demonstrate clear understanding of the FPS-R and its response
      scale. Overall, children aged >=7 years understood the instrument and could
      complete it on the electronic device, although children aged 7-8 often needed
      assistance from the parent. Children aged 9-17 years were able to read and
      complete the instrument independently. Most participants considered the
      electronic device easy to use. CONCLUSIONS: The FPS-R was shown to be a
      comprehensible and usable pain measure for children aged 7-17 with SCD and to be
      beneficial for future clinical studies.

PMID- 27026182
TI  - Nursing Performance and Mobile Phone Use: Are Nurses Aware of Their Performance
      Decrements?
AB  - BACKGROUND: Prior research has documented the effect of concurrent mobile phone
      use on medical care. This study examined the extent of hospital registered
      nurses' awareness of their mobile-phone-associated performance decrements.
      OBJECTIVE: The objective of this study was to compare self-reported performance
      with reported observed performance of others with respect to mobile phone use by
      hospital registered nurses. METHODS: In March 2014, a previously validated survey
      was emailed to the 10,978 members of the Academy of Medical Surgical Nurses. The
      responses were analyzed using a two-proportion z test (alpha=.05, two-tailed) to
      examine whether self-reported and observed rates of error were significantly
      different. All possible demographic and employment confounders which could
      potentially contribute to self-reported and observed performance errors were
      tested for significance. RESULTS: Of the 950 respondents, 825 (8.68%, 825/950)
      met the inclusion criteria for analysis. The representativeness of the sample
      relative to the US nursing workforce was assessed using a two-proportion z test.
      This indicated that sex and location of primary place of employment (urban/rural)
      were represented appropriately in the study sample. Respondents in the age groups
      <40 years old were underrepresented, while age groups >55 years old were
      overrepresented. Whites, American Indians/Alaskan natives, and Native Hawaiian or
      Pacific Islanders were underrepresented, while Hispanic and multiple/other
      ethnicities were overrepresented. It was decided to report the unweighted, rather
      than the weighted survey data, with the recognition that the results, while
      valuable, may not be generalizable to the entire US registered nursing workforce.
      A significant difference was found between registered nurses' self-reported and
      observed rates of errors associated with concurrent mobile phone use in following
      three categories (1) work performance (z=-26.6142, P<.001, Fisher's exact test),
      (2) missing important clinical information (z=-13.9882, P=.008, Fisher's exact
      test), and (3) making a medical error (z=-9.6798, P<.001, Fisher's exact test).
      Respondents reported that personal mobile phone use by nurses at work was a
      serious distraction; always (13%, 107/825), often (29.6%, 244/825), sometimes
      (44.6%, 368/825), rarely (8.7%, 72/825), or never (1.2%, 10/825). On balance,
      69.5% (573/825) of respondents believed that nurses' use of personal mobile
      phones while working had a negative effect on patient care. Since all possible
      confounders were tested and none were deemed significant, a multivariate analysis
      was not considered necessary. CONCLUSIONS: Many hospitals are drawing up policies
      that allow workers to decide how to use their devices at work. This study found
      that nurses express a disproportionately high confidence in their ability to
      manage the risk associated with the use of mobile phones and may not be able to
      accurately assess when it is appropriate to use these devices at work.

PMID- 27026181
TI  - Novel double-stapling technique for distal oesophageal resection and oesophago
      jejunal anastomosis.
AB  - AIM: The restoration of the digestive tract by performing an esophago-jejunal
      anastomosis (EJA) is a crucial step of the total gastric and distal esophagus
      surgical resection for esophago-gastric junction (EGJ) cancer. We have already
      ideated and tested on a cadaver model an innovative technique which could be
      useful to minimize the risk of complications related to the phase of securing the
      anvil of the circular stapler prior to perform the EJA. This surgical technique
      was derived from the well-known "double-stapling Knight and Griffen" one that was
      described for the rectal resection. We used the following described technique in
      20 patients with EGJ cancer and it is efficient, reliable, safe, easy to learn
      and easy to perform. MATERIALS AND METHODS: From August 2014 to May 2015, 20
      patients (14 male and 6 female) underwent surgery for esophagogastric junction
      cancer: In all patients a distal esophageal resection and total gastrectomy was
      performed. Through the trans-hiatal access, the free margins of the esophageal
      stump were suspended and the anvil of a circular stapler on a new dedicated and
      registered support bar was inserted into the lumen. Subsequently, the linear
      suturing stapler is closed over the bar and then fired to suture the distal stump
      of the esophagus; after the confirmation of a negative margin, the bar is
      retracted and the push-rod of the anvil is pulled out through the linear suture.
      Finally, the anastomosis is performed with the classic technique by using a
      circular stapler. RESULTS: No postoperative mortality occurred; postoperative
      course has been uneventful for 18 patients. One patient developed anastomotic
      fistula that has been treated conservatively with endoscopic prothesis, removed
      after 20 days. One patient developed in 3 POD myocardial infarction Mean Hospital
      stay has been 14 days (range 7-20 days). CONCLUSIONS: The aim of our new
      procedure is the insertion the anvil of a common circular stapler without
      handsewn securing; this is to reduce the technical difficulties related to the
      hand-sewn securing into a deep and narrow anatomic location, typical of the trans
      hiatal approach. KEY WORDS: Anastomosis, Oesophago-gastric junction cancer,
      Stapler, Trans-hiatal.

PMID- 27026183
TI  - Albumin and Protein Oxidation are Predictors that Differentiate Relapsing
      Remitting from Progressive Clinical Forms of Multiple Sclerosis.
AB  - The aim of the present study was to evaluate inflammatory, oxidative, and
      nitrosative stress (IO&NS) blood markers as possible predictors of multiple
      sclerosis (MS) and its clinical forms. This study included 258 MS patients (175
      with relapsing-remitting MS (RRMS) and 83 with progressive MS clinical forms) and
      249 healthy individuals. Peripheral blood samples were obtained to determine
      serum levels of albumin, ferritin, C-reactive protein (CRP), total protein, lipid
      hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH),
      carbonyl protein content, advanced oxidation protein products (AOPP), nitric
      oxide metabolites (NOx), and total radical-trapping antioxidant parameter (TRAP).
      MS patients showed higher ferritin (p < 0.001) and CL-LOOH (p < 0.001) and lower
      albumin (p = 0.001), TRAP (p < 0.001), AOPP (p = 0.013), and NOx values (p <
      0.001) than controls. Difference was not observed in CRP, total protein, and
      carbonyl proteins between patients and controls. In the logistic regression age
      adjusted, ferritin and CL-LOOH showed positive association with MS and were
      predictors of MS development (OR: 1.006, 95 % CI: 1.003-1.009, p < 0.001 and OR:
      1.029, 95 % CI: 1.007-1.052, p = 0.009, respectively). Albumin, TRAP, AOPP, and
      NOx were negatively associated with MS (p = 0.019, p = 0.003, p = 0.001, and p =
      0.003, respectively). Moreover, other logistic regression age-adjusted showed
      that MS patients with progressive clinical forms had lower albumin and higher
      AOPP than those with RRMS (p = 0.037). In conclusion, ferritin, albumin, and
      biomarkers of IO&NS, such as CL-LOOH, AOPP, TRAP, and NOx were predictors of MS
      diagnosis, whereas albumin and AOPP were predictors that differentiated RRMS from
      the progressive clinical forms of MS.

PMID- 27026186
TI  - Interprofessional education in Brazil: Building synergic networks of educational
      and healthcare processes.

PMID- 27026184
TI  - Hippocampal Astrocyte Cultures from Adult and Aged Rats Reproduce Changes in
      Glial Functionality Observed in the Aging Brain.
AB  - Astrocytes are dynamic cells that maintain brain homeostasis, regulate
      neurotransmitter systems, and process synaptic information, energy metabolism,
      antioxidant defenses, and inflammatory response. Aging is a biological process
      that is closely associated with hippocampal astrocyte dysfunction. In this sense,
      we demonstrated that hippocampal astrocytes from adult and aged Wistar rats
      reproduce the glial functionality alterations observed in aging by evaluating
      several senescence, glutamatergic, oxidative and inflammatory parameters commonly
      associated with the aging process. Here, we show that the p21 senescence
      associated gene and classical astrocyte markers, such as glial fibrillary acidic
      protein (GFAP), vimentin, and actin, changed their expressions in adult and aged
      astrocytes. Age-dependent changes were also observed in glutamate transporters
      (glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)) and
      glutamine synthetase immunolabeling and activity. Additionally, according to in
      vivo aging, astrocytes from adult and aged rats showed an increase in
      oxidative/nitrosative stress with mitochondrial dysfunction, an increase in RNA
      oxidation, NADPH oxidase (NOX) activity, superoxide levels, and inducible nitric
      oxide synthase (iNOS) expression levels. Changes in antioxidant defenses were
      also observed. Hippocampal astrocytes also displayed age-dependent inflammatory
      response with augmentation of proinflammatory cytokine levels, such as TNF-alpha,
      IL-1beta, IL-6, IL-18, and messenger RNA (mRNA) levels of cyclo-oxygenase 2 (COX
      2). Furthermore, these cells secrete neurotrophic factors, including glia-derived
      neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), S100
      calcium-binding protein B (S100B) protein, and transforming growth factor-beta
      (TGF-beta), which changed in an age-dependent manner. Classical signaling
      pathways associated with aging, such as nuclear factor erythroid-derived 2-like 2
      (Nrf2), nuclear factor kappa B (NFkappaB), heme oxygenase-1 (HO-1), and p38
      mitogen-activated protein kinase (MAPK), were also changed in adult and aged
      astrocytes and are probably related to the changes observed in senescence marker,
      glutamatergic metabolism, mitochondrial dysfunction, oxidative/nitrosative
      stress, antioxidant defenses, inflammatory response, and trophic factors release.
      Together, our results reinforce the role of hippocampal astrocytes as a target
      for understanding the mechanisms involved in aging and provide an innovative tool
      for studies of astrocyte roles in physiological and pathological aging brain.

PMID- 27026187
TI  - Staff perception of interprofessional working relationships after a work redesign
      intervention in a Danish orthopaedic hand unit outpatient clinic.
AB  - There is evidence that clinical pathways improve quality of care; however,
      knowledge is limited concerning the influence on and the benefits experienced by
      the interprofessional teams working with these pathways. Our working methods in a
      hand unit in an orthopaedic outpatient clinic in Denmark were redesigned to
      include, among other changes, the introduction of clinical pathways. Changes
      included standardising treatment and communication methods, delegating tasks from
      medical specialists to nurses, and providing nurses with their own consultation
      room. Using focus group interviews before and after the implementation of the new
      working methods, we investigated staff-perceived experiences of the effects on
      working relationships and the utilisation of professional skills and attitudes,
      resulting from the mentioned change in working methods. The results were changes
      in daily communication methods among healthcare staff and improvements in the
      actual communication and collaborative problem solving skills concerning standard
      patients with simple hand pathology; however, there are still challenges for
      patients with more complex hand pathology. Though this new interprofessional
      arrangement improves the use of nurse and medical specialist professional
      competencies, it also requires a high degree of trust among the team members. 

PMID- 27026185
TI  - Homogeneity and heterogeneity in amylase production by Bacillus subtilis under
      different growth conditions.
AB  - BACKGROUND: Bacillus subtilis is an important cell factory for the
      biotechnological industry due to its ability to secrete commercially relevant
      proteins in large amounts directly into the growth medium. However, hyper
      secretion of proteins, such as alpha-amylases, leads to induction of the
      secretion stress-responsive CssR-CssS regulatory system, resulting in up
      regulation of the HtrA and HtrB proteases. These proteases degrade misfolded
      proteins secreted via the Sec pathway, resulting in a loss of product. The aim of
      this study was to investigate the secretion stress response in B. subtilis 168
      cells overproducing the industrially relevant alpha-amylase AmyM from Geobacillus
      stearothermophilus, which was expressed from the strong promoter P(amyQ)-M.
      RESULTS: Here we show that activity of the htrB promoter as induced by
      overproduction of AmyM was "noisy", which is indicative for heterogeneous
      activation of the secretion stress pathway. Plasmids were constructed to allow
      real-time analysis of P(amyQ)-M promoter activity and AmyM production by,
      respectively, transcriptional and out-of-frame translationally coupled fusions
      with gfpmut3. Our results show the emergence of distinct sub-populations of high-
      and low-level AmyM-producing cells, reflecting heterogeneity in the activity of
      P(amyQ)-M. This most likely explains the heterogeneous secretion stress response.
      Importantly, more homogenous cell populations with regard to P(amyQ)-M activity
      were observed for the B. subtilis mutant strain 168degUhy32, and the wild-type
      strain 168 under optimized growth conditions. CONCLUSION: Expression
      heterogeneity of secretory proteins in B. subtilis can be suppressed by degU
      mutation and optimized growth conditions. Further, the out-of-frame translational
      fusion of a gene for a secreted target protein and gfp represents a versatile
      tool for real-time monitoring of protein production and opens novel avenues for
      Bacillus production strain improvement.

PMID- 27026188
TI  - Student perceptions towards interprofessional education: Findings from a
      longitudinal study based in a Middle Eastern university.
AB  - The Lebanese American University Interprofessional Education (LAU IPE) Steps
      Framework consists of a five-step workshop-based series that is offered
      throughout the curriculum of health and social care students at an American
      university in Lebanon. The aim of the present study was to report students'
      perceptions of their readiness for interprofessional learning before and after
      completing the IPE steps, their evaluations of interprofessional learning
      outcomes, as well as their satisfaction with the learning experience as a whole.
      A longitudinal survey design was used: questionnaires were completed by students
      before IPE exposure and after each step. The results showed that before IPE
      exposure, students' perceptions of their readiness for interprofessional learning
      were generally favourable, with differences across genders (stronger professional
      identity in females compared to males) and across professions (higher teamwork
      and collaboration in pharmacy and nutrition students compared to other
      professions and lower patient centredness in nursing students compared to
      others). After participation in the IPE steps, students showed enhanced readiness
      for interprofessional learning and differences between genders and professions
      decreased. Participants were satisfied with the learning experience and
      assessment scores showed that all IPE learning outcomes were met. The LAU IPE
      Steps Framework may be of value to other interprofessional education course
      developers. 

PMID- 27026189
TI  - A longitudinal study of health professional students' attitudes towards
      interprofessional education at an American university.
AB  - Efforts to improve interprofessional education (IPE) are informed by attitudes of
      health professional students, yet there are limited US data on student
      characteristics and experiences associated with positive attitudes towards IPE. A
      cohort of US medical, nursing, and physician associate students was surveyed in
      their first and third years, using the Readiness for Interprofessional Learning
      Scale and Interdisciplinary Education Perception Scale. Information was also
      collected on demographics and experiences during training. Health professional
      students differed in their attitudes towards IPE; characteristics associated with
      having more positive attitudes at both time points included being a nursing
      student, female, older, and having more previous healthcare experience. Students
      who participated in interprofessional extracurricular activities (particularly
      patient-based activities) during training reported more positive attitudes in the
      third year than those who did not participate in such activities. Based on these
      findings, schools may consider how student characteristics and participation in
      interprofessional extracurricular activities can affect attitudes regarding IPE.
      Building on the positive elements of this interprofessional extracurricular
      experience, schools may also want to consider service-learning models of IPE
      where students work together on shared goals. 

PMID- 27026190
TI  - A review of instruments to measure interprofessional collaboration for chronic
      disease management for community-living older adults.
AB  - It is acknowledged internationally that chronic disease management (CDM) for
      community-living older adults (CLOA) is an increasingly complex process. CDM for
      older adults, who are often living with multiple chronic conditions, requires
      coordination of various health and social services. Coordination is enabled
      through interprofessional collaboration (IPC) among individual providers,
      community organizations, and health sectors. Measuring IPC is complicated given
      there are multiple conceptualisations and measures of IPC. A literature review of
      several healthcare, psychological, and social science electronic databases was
      conducted to locate instruments that measure IPC at the team level and have
      published evidence of their reliability and validity. Five instruments met the
      criteria and were critically reviewed to determine their strengths and
      limitations as they relate to CDM for CLOA. A comparison of the characteristics,
      psychometric properties, and overall concordance of each instrument with salient
      attributes of IPC found the Collaborative Practice Assessment Tool to be the most
      appropriate instrument for measuring IPC for CDM in CLOA. 

PMID- 27026191
TI  - An interprofessional exploration of nursing and social work roles when working
      jointly with families.
AB  - Ngala, an early parenting not-for-profit organisation in Western Australia, has
      provided services to families with young children since 1890. Child health nurses
      and mothercraft nurses were the primary workforce until the 1980s when a social
      worker was employed and a new era of interprofessional collaboration began.
      Evidence to date has focused on nursing workforce, interprofessional education,
      and interprofessional teams. Little is known about the roles of nursing and
      social work when working jointly with families. A new service commenced in 2012
      for families with children with developmental delays. Social workers and child
      health nurses were employed for this service model. Our study aim was to explore
      the perceptions of how nurses and social workers work together with a family
      providing psychosocial support across a new service. The study was conducted
      alongside implementation of this new service. An exploratory case study approach
      was adopted to generate an in-depth understanding of the roles of nurses and
      social workers. In total, 22 semi-structured interviews and one focus group
      across the first year of implementing the new service were undertaken. Analysis
      of these data revealed four major themes. Findings presented in this article will
      inform further reflection and consideration into the future interprofessional
      workforce priorities and requirements for Early Parenting Services. 

PMID- 27026192
TI  - Interprofessional team building in the palliative home care setting: Use of a
      conceptual framework to inform a pilot evaluation.
AB  - Home-based palliative care is increasingly dependent on interprofessional teams
      to deliver collaborative care that more adequately meets the needs of clients and
      families. The purpose of this pilot evaluation was to qualitatively explore the
      views of an interprofessional group of home care providers (occupational
      therapists, nurses, personal support work supervisors, community care
      coordinators, and a team coordinator) regarding a pilot project encouraging
      teamwork in interprofessional palliative home care services. We used qualitative
      methods, informed by an interprofessional conceptual framework, to analyse
      participants' accounts and provide recommendations regarding strategies for
      interprofessional team building in palliative home health care. Findings suggest
      that encouraging practitioners to share past experiences and foster common goals
      for palliative care are important elements of team building in interprofessional
      palliative care. Also, establishing a team leader who emphasises sharing power
      among team members and addressing the need for mutual emotional support may help
      to maximise interprofessional teamwork in palliative home care. These findings
      may be used to develop and test more comprehensive efforts to promote stronger
      interprofessional teamwork in palliative home health care delivery. 

PMID- 27026193
TI  - Corrigendum.

PMID- 27026194
TI  - Intracellular osteopontin stabilizes TRAF3 to positively regulate innate
      antiviral response.
AB  - Osteopontin (OPN) is a multifunctional protein involved in both innate immunity
      and adaptive immunity. However, the function of OPN, especially the intracellular
      form OPN (iOPN) on innate antiviral immune response remains elusive. Here, we
      demonstrated that iOPN is an essential positive regulator to protect the host
      from virus infection. OPN deficiency or knockdown significantly attenuated virus
      induced IRF3 activation, IFN-beta production and antiviral response.
      Consistently, OPN-deficient mice were more susceptible to VSV infection than WT
      mice. Mechanistically, iOPN was found to interact with tumor necrosis factor
      receptor (TNFR)-associated factor 3 (TRAF3) and inhibit Triad3A-mediated K48
      linked polyubiquitination and degradation of TRAF3 through the C-terminal
      fragment of iOPN. Therefore, our findings delineated a new function for iOPN to
      act as a positive regulator in innate antiviral immunity through stabilization of
      TRAF3. 

PMID- 27026195
TI  - NRP2 transcriptionally regulates its downstream effector WDFY1.
AB  - Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors
      for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of
      NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells,
      a function distinctly different from its role as a co-receptor. WD Repeat and
      FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this
      function. Our results indicated that NRP2 maintains an optimum concentration of
      WDFY1 by negatively regulating its expression. Since increased expression of
      WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in
      metastatic cancer cells to sustain high endocytic activity, essential for
      promotion of oncogenic activation and cancer cell survival. Here, we have
      delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our
      results indicated that NRP2 inhibits WDFY1 transcription by preventing the
      nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1
      (FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis
      has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis
      is a critical event in maintaining metastatic phenotype in cancer cells. Thus,
      inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce
      cell death in metastatic cancer. 

PMID- 27026196
TI  - Serum Brain-Derived Neurotrophic Factor Mediates the Relationship between
      Abdominal Adiposity and Executive Function in Middle Age.
AB  - OBJECTIVES: Excessive adipose tissue, especially in the abdominal area, is
      associated with increased risk of dementia in older adults. However, the
      mechanisms underlying this relationship are poorly understood. As increased
      adiposity is also associated with lower circulating levels of brain-derived
      neurotrophic factor (BDNF), a key molecule modulating brain plasticity and
      neuronal regeneration, we hypothesized that the changes in cognition that occur
      as a result of excessive abdominal adiposity would be driven by lower levels of
      circulating BDNF. METHODS: Fasting blood samples were obtained from 60
      participants aged 40-60 years (mean+/-SD=52.3+/-5.6) and BDNF levels were
      assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was
      measured using a ratio of waist circumference to hip circumference (WHR).
      Participants also completed a neuropsychological assessment battery to assess
      executive function. Statistical mediation was assessed using traditional causal
      steps and nonparametric bootstrapping. RESULTS: Higher WHR was significantly
      associated with poorer performance on the Controlled Oral Word Association (COWA)
      letter fluency test (beta=-0.489; p=.003) and lower levels of circulating BDNF
      (beta=-0.345; p=.006). Linear regression and bootstrapping methods indicated that
      BDNF fully mediated the relationship between WHR and performance on the COWA
      (beta=0.60; 95% confidence interval [-3.79, -0.26]). CONCLUSIONS: The
      relationship between higher WHR and verbal fluency was fully statistically
      mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable
      mechanism through which executive function decline occurs in individuals with
      high abdominal adiposity. BDNF enhancing interventions (physical exercise and
      dietary restriction) could thus be used to improve executive function in these
      individuals.

PMID- 27026197
TI  - Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of
      Pancreatic Cancer.
AB  - PURPOSE: Pancreatic adenocarcinoma is a highly aggressive cancer, currently
      treated with limited success and dismal outcomes. New diagnostic and treatment
      strategies offer the potential to reduce cancer mortality. Developing highly
      specific noninvasive imaging probes for pancreatic cancer is essential to
      improving diagnostic accuracy and monitoring therapeutic intervention.
      EXPERIMENTAL DESIGN: A bispecific heterodimer was synthesized by conjugating an
      anti-tissue factor (TF) Fab with an anti-CD105 Fab, via the bio-orthogonal
      "click" reaction between tetrazine (Tz) and trans-cyclooctene (TCO). The
      heterodimer was labeled with (64)Cu for PET imaging of nude mice bearing BXPC-3
      xenograft and orthotopic pancreatic tumors. RESULTS: PET imaging of BXPC-3
      (TF/CD105(+/+)) xenograft tumors with (64)Cu-labeled heterodimer displayed
      significantly enhanced tumor uptake (28.8 +/- 3.2 %ID/g; n = 4; SD) at 30 hours
      postinjection, as compared with each of their monospecific Fab tracers (12.5 +/-
      1.4 and 7.1 +/- 2.6 %ID/g; n = 3; SD). In addition, the activity-concentration
      ratio allowed for effective tumor visualization (tumor/muscle ratio 75.2 +/- 9.4
      at 30 hours postinjection.; n = 4; SD). Furthermore, (64)Cu-NOTA-heterodimer
      enabled sensitive detection of orthotopic pancreatic tumor lesions with an uptake
      of 17.1 +/- 4.9 %ID/g at 30 hours postinjection and tumor/muscle ratio of 72.3 +/
      46.7. CONCLUSIONS: This study demonstrates that dual targeting of TF and CD105
      provided synergistic improvements in binding affinity and tumor localization of
      the heterodimer. Dual-targeted imaging agents of pancreatic and other cancers may
      assist in diagnosing pancreatic malignancies as well as reliable monitoring of
      therapeutic response. Clin Cancer Res; 22(15); 3821-30. (c)2016 AACR.

PMID- 27026199
TI  - Development and Validation of Urine-based Peptide Biomarker Panels for Detecting
      Bladder Cancer in a Multi-center Study.
AB  - PURPOSE: Urothelial bladder cancer presents high recurrence rates, mandating
      continuous monitoring via invasive cystoscopy. The development of noninvasive
      tests for disease diagnosis and surveillance remains an unmet clinical need. In
      this study, validation of two urine-based biomarker panels for detecting primary
      and recurrent urothelial bladder cancer was conducted. EXPERIMENTAL DESIGN: Two
      studies (total n = 1,357) were performed for detecting primary (n = 721) and
      relapsed urothelial bladder cancer (n = 636). Cystoscopy was applied for
      detecting urothelial bladder cancer, while patients negative for recurrence had
      follow-up for at least one year to exclude presence of an undetected tumor at the
      time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS)
      was employed for the identification of urinary peptide biomarkers. The candidate
      urine-based peptide biomarker panels were derived from nested cross-sectional
      studies in primary (n = 451) and recurrent (n = 425) urothelial bladder cancer.
      RESULTS: Two biomarker panels were developed on the basis of 116 and 106 peptide
      biomarkers using support vector machine algorithms. Validation of the urine-based
      biomarker panels in independent validation sets, resulted in AUC values of 0.87
      and 0.75 for detecting primary (n = 270) and recurrent urothelial bladder cancer
      (n = 211), respectively. At the optimal threshold, the classifier for detecting
      primary urothelial bladder cancer exhibited 91% sensitivity and 68% specificity,
      while the classifier for recurrence demonstrated 87% sensitivity and 51%
      specificity. Particularly for patients undergoing surveillance, improved
      performance was achieved when combining the urine-based panel with cytology (AUC
      = 0.87). CONCLUSIONS: The developed urine-based peptide biomarker panel for
      detecting primary urothelial bladder cancer exhibits good performance.
      Combination of the urine-based panel and cytology resulted in improved
      performance for detecting disease recurrence. Clin Cancer Res; 22(16); 4077-86.
      (c)2016 AACR.

PMID- 27026198
TI  - Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult
      Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer.
AB  - PURPOSE: Preclinical data support combining AKT inhibitors with HER2-targeted
      therapies to overcome resistance to treatment. This phase I study combined the
      investigational AKT inhibitor, MK-2206, with lapatinib to determine the MTD.
      EXPERIMENTAL DESIGN: The dose escalation cohort enrolled adults with advanced
      solid tumors, who received MK-2206 dosed 30 to 60 mg every other day and
      lapatinib 1,000 to 1,500 mg daily continuously, escalated using a 3+3 design.
      Cycles were 28 days except cycle 1 (35 days, including an initial 8 days of MK
      2206 alone to evaluate pharmacokinetic interactions). The dose expansion cohort
      enrolled adults with advanced HER2(+) breast cancer. RESULTS: Twenty-three
      participants enrolled in the dose escalation cohort. Dose-limiting toxicities
      were hyponatremia, fatigue, rash, hypocalcemia, and mucositis. Common toxicities
      included diarrhea, nausea, and rash. The MTD was reached at MK-2206 45 mg orally
      every other day and lapatinib 1,500 mg orally daily. Two participants maintained
      stable disease for >4 months, including a colorectal cancer participant with
      substantial carcinoembryonic antigen decrease. Of 5 participants in the dose
      expansion cohort, 2 maintained stable disease for >6 months, including one with
      prior progression on single-agent lapatinib. Plasma MK-2206 concentrations
      decreased after addition of lapatinib, but in vitro studies indicate lapatinib
      increases the intracellular levels of MK-2206. CONCLUSIONS: MK-2206 combined with
      lapatinib can be tolerated with both drugs above biologically active single-agent
      doses. Overlapping toxicities result in significant diarrhea and rash, which can
      be managed medically. Antitumor activity was promising and supports evaluation of
      AKT inhibitors combined with HER2-targeted therapies. Clin Cancer Res; 22(11);
      2659-67. (c)2016 AACR.

PMID- 27026200
TI  - Carfilzomib Triggers Cell Death in Chronic Lymphocytic Leukemia by Inducing
      Proapoptotic and Endoplasmic Reticulum Stress Responses.
AB  - PURPOSE: Carfilzomib, while active in B-cell neoplasms, displayed heterogeneous
      response in chronic lymphocytic leukemia (CLL) samples from patients and showed
      interpatient variability to carfilzomib-induced cell death. To understand this
      variability and predict patients who would respond to carfilzomib, we
      investigated the mechanism by which carfilzomib induces CLL cell death.
      EXPERIMENTAL DESIGN: Using CLL patient samples and cell lines, complementary
      knockdown and knockout cells, and carfilzomib-resistant cell lines, we evaluated
      changes in intracellular networks to identify molecules responsible for
      carfilzomib's cytotoxic activity. Lysates from carfilzomib-treated cells were
      immunoblotted for molecules involved in ubiquitin, apoptotic, and endoplasmic
      reticulum (ER) stress response pathways and results correlated with carfilzomib
      cytotoxic activity. Coimmunoprecipitation and pull-down assays were performed to
      identify complex interactions among MCL-1, Noxa, and Bak. RESULTS: Carfilzomib
      triggered ER stress and activation of both the intrinsic and extrinsic apoptotic
      pathways through alteration of the ubiquitin proteasome pathway. Consequently,
      the transcription factor CCAAT/enhancer-binding protein homology protein (CHOP)
      accumulated in response to carfilzomib, and CHOP depletion conferred protection
      against cytotoxicity. Carfilzomib also induced accumulation of MCL-1 and Noxa,
      whereby MCL-1 preferentially formed a complex with Noxa and consequently relieved
      MCL-1's protective effect on sequestering Bak. Accordingly, depletion of Noxa or
      both Bak and Bax conferred protection against carfilzomib-induced cell death.
      CONCLUSIONS: Collectively, carfilzomib induced ER stress culminating in
      activation of intrinsic and extrinsic caspase pathways, and we identified the
      CHOP protein level as a biomarker that could predict sensitivity to carfilzomib
      in CLL. Clin Cancer Res; 22(18); 4712-26. (c)2016 AACR.

PMID- 27026201
TI  - DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor,
      Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.
AB  - PURPOSE: An anti-HER2 antibody-drug conjugate with a novel topoisomerase I
      inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its
      preclinical pharmacologic profile was assessed. EXPERIMENTAL DESIGN: In vitro and
      in vivo pharmacologic activities of DS-8201a were evaluated and compared with T
      DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX)
      models. The mechanism of action for the efficacy was also evaluated.
      Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and
      cynomolgus monkeys were assessed. RESULTS: DS-8201a exhibited a HER2 expression
      dependent cell growth-inhibitory activity and induced tumor regression with a
      single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87
      model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable
      with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity
      to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone
      H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS
      8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in
      cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS
      8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression.
      DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast
      cancer PDX models with low HER2 expression. CONCLUSIONS: DS-8201a exhibited a
      potent antitumor activity in a broad selection of HER2-positive models and
      favorable pharmacokinetics and safety profiles. The results demonstrate that DS
      8201a will be a valuable therapy with a great potential to respond to T-DM1
      insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer
      Res; 22(20); 5097-108. (c)2016 AACR.

PMID- 27026204
TI  - Capturing the diagnosis of chronic renal insufficiency in the electronic medical
      record and its influence on therapeutic management.

PMID- 27026207
TI  - Using a competition model to help rural communities become healthier: lessons
      from the NSW Healthy Town Challenge quality assurance process.

PMID- 27026206
TI  - Effects of hydrogen-rich water on depressive-like behavior in mice.
AB  - Emerging evidence suggests that neuroinflammation and oxidative stress may be
      major contributors to major depressive disorder (MDD). Patients or animal models
      of depression show significant increase of proinflammatory cytokine interleukin
      1beta (IL-1beta) and oxidative stress biomarkers in the periphery or central
      nervous system (CNS). Recent studies show that hydrogen selectively reduces
      cytotoxic oxygen radicals, and hydrogen-rich saline potentially suppresses the
      production of several proinflammatory mediators. Since current depression
      medications are accompanied by a wide spectrum of side effects, novel
      preventative or therapeutic measures with fewer side effects might have a
      promising future. We investigated the effects of drinking hydrogen-rich water on
      the depressive-like behavior in mice and its underlying mechanisms. Our study
      show that hydrogen-rich water treatment prevents chronic unpredictable mild
      stress (CUMS) induced depressive-like behavior. CUMS induced elevation in IL
      1beta protein levels in the hippocampus, and the cortex was significantly
      attenuated after 4 weeks of feeding the mice hydrogen-rich water. Over-expression
      of caspase-1 (the IL-1beta converting enzyme) and excessive reactive oxygen
      species (ROS) production in the hippocampus and prefrontal cortex (PFC) was
      successfully suppressed by hydrogen-rich water treatment. Our data suggest that
      the beneficial effects of hydrogen-rich water on depressive-like behavior may be
      mediated by suppression of the inflammasome activation resulting in attenuated
      protein IL-1beta and ROS production. 

PMID- 27026208
TI  - Autologous bone grafting with platelet-rich plasma for alveolar cleft repair in
      patient with cleft and palate.
AB  - PURPOSE: Bone grafting of the alveolus has become an essential part of the
      contemporary surgical management of the oral cleft. The aim of this retrospective
      study was to evaluate the results of bone grafting in association with PRP
      (plateletrich plasma) to enhance osteogenesis and osteointegration. PATIENTS AND
      METHODS: The study included 16 patients, aged between 9 and 11, affected with
      unilateral residual alveolar clefts, who underwent bone grafting using secondary
      alveoplasty. The eight patients belonging to the control group were administered
      autologous bone graft alone while the study group, consisting of 8 patients,
      underwent autologous bone grafting in association with PRP. All patients had pre
      and post surgery orthodontic treatment. The statistical analyses included
      Student's t test, 2 test and Kaplan-Meir time to event analysis. The p-value was
      considered significant if p<0.05. All statistical analyses were performed using
      SAS Software release 9.3 (SAS Institute, Cary, Nc). RESULTS: The control group (M
      50%, mean age 10.2+/-2.3) underwent simple autologous bone graft while the study
      group (M 62.5%, mean age 9.9+/-2.2) was treated with a combination of autologous
      bone and PRP. No statistically significant differences were found between the two
      groups as regards age, gender and labial-palatal cleft clinical characteristics.
      6, 12, 24 month follow-ups were performed by means of clinical and radiographic
      investigations. None of the study group developed oronasal fistulas or
      experienced bone height, bone bridging and bone quality loss; only two patients
      developed mild periodontal problems. The study group was able to undergo a
      significantly (p<0.001) earlier and shorter orthodontic treatment. CONCLUSIONS:
      In our experience, the use of PRP enhances the quality of osteoplasty,
      accelerates "creeping substitution" and bone healing and favours earlier
      orthodontic treatment. KEY WORDS: Alveolar cleft, Bone grafting, Palate, Platelet
      rich plasma.

PMID- 27026209
TI  - Mechanisms-based viscoplasticity: Theoretical approach and experimental
      validation for steel 304L.
AB  - We propose a mechanisms-based viscoplasticity approach for metals and alloys.
      First, we derive a stochastic model for thermally-activated motion of
      dislocations and, then, introduce power-law flow rules. The overall plastic
      deformation includes local plastic slip events taken with an appropriate weight
      assigned to each angle of the plane misorientation from the direction of maximum
      shear stress. As deformation progresses, the material experiences successive
      reorganizations of the slip systems. The microstructural evolution causes that a
      portion of energy expended on plastic deformation is dissipated and the rest is
      stored in the defect structures. We show that the reorganizations are stable in a
      homogeneously deformed material. The concept is tested for steel 304L, where we
      reproduce experimentally obtained stress-strain responses, we construct the Frost
      Ashby deformation map and predict the rate of the energy storage. The storage is
      assessed in terms of synchronized measurements of temperature and displacement
      distributions on the specimen surface during tensile loading. 

PMID- 27026210
TI  - Mental Health Technologies: Designing With Consumers.
AB  - Despite growing interest in the promise of e-mental and well-being interventions,
      little supporting literature exists to guide their design and the evaluation of
      their effectiveness. Both participatory design (PD) and design thinking (DT) have
      emerged as approaches that hold significant potential for supporting design in
      this space. Each approach is difficult to definitively circumscribe, and as such
      has been enacted as a process, a mind-set, specific practices/techniques, or a
      combination thereof. At its core, however, PD is a design research tradition that
      emphasizes egalitarian partnerships with end users. In contrast, DT is in the
      process of becoming a management concept tied to innovation with strong roots in
      business and education. From a health researcher viewpoint, while PD can be
      reduced to a number of replicable stages that involve particular methods,
      techniques, and outputs, projects often take vastly different forms and effective
      PD projects and practice have traditionally required technology-specific (eg,
      computer science) and domain-specific (eg, an application domain, such as patient
      support services) knowledge. In contrast, DT offers a practical off-the-shelf
      toolkit of approaches that at face value have more potential to have a quick
      impact and be successfully applied by novice practitioners (and those looking to
      include a more human-centered focus in their work). Via 2 case studies we explore
      the continuum of similarities and differences between PD and DT in order to
      provide an initial recommendation for what health researchers might reasonably
      expect from each in terms of process and outcome in the design of e-mental health
      interventions. We suggest that the sensibilities that DT shares with PD (ie, deep
      engagement and collaboration with end users and an inclusive and
      multidisciplinary practice) are precisely the aspects of DT that must be
      emphasized in any application to mental health provision and that any technology
      development process must prioritize empathy and understanding over innovation for
      the successful uptake of technology in this space. 

PMID- 27026202
TI  - "Targeting astrocytes in CNS injury and disease: A translational research
      approach".
AB  - Astrocytes are a major constituent of the central nervous system. These glia play
      a major role in regulating blood-brain barrier function, the formation and
      maintenance of synapses, glutamate uptake, and trophic support for surrounding
      neurons and glia. Therefore, maintaining the proper functioning of these cells is
      crucial to survival. Astrocyte defects are associated with a wide variety of
      neuropathological insults, ranging from neurodegenerative diseases to gliomas.
      Additionally, injury to the CNS causes drastic changes to astrocytes, often
      leading to a phenomenon known as reactive astrogliosis. This process is important
      for protecting the surrounding healthy tissue from the spread of injury, while it
      also inhibits axonal regeneration and plasticity. Here, we discuss the important
      roles of astrocytes after injury and in disease, as well as potential therapeutic
      approaches to restore proper astrocyte functioning.

PMID- 27026211
TI  - Effect of stabilization splint therapy on glenoid fossa remodeling in
      temporomandibular joint osteoarthritis.
AB  - PURPOSE: The aim of this study was to evaluate, by CBCT superimposition, bone
      changes (cortical bone intactness, sclerosis and subchondral cyst) in the glenoid
      fossa related to stabilization splint (SS) therapy for temporomandibular joint
      osteoarthritis (TMJ OA) patients and to compare the effects for two groups, one
      that had undergone SS therapy and the other that had not. METHODS: This case
      control study included 36 TMJ OA patients, 10 that had undergone SS therapy (the
      SS group) compared with 26 that had not (the non-SS group). Osseous changes in
      the glenoid fossa were evaluated based on superimposed CBCT images before and
      after treatment. RESULTS: Improvements ranging from 57.5 to 100% were achieved in
      cortical bone integrity, sclerosis, and subchondral cyst for both groups, SS and
      non-SS. However, there were no statistically significant difference between the
      two groups (p>0.05). The non-SS group showed a significant decrease in the
      distances from the point of inflexion and the lowest point of the articular
      eminence to the reference line (p<0.05). On the other hand, the SS group showed
      an increase for the point of inflexion. The other measures showed no
      statistically significant differences in distance before treatment and after
      treatment, even though the average distance after treatment showed an overall
      increasing tendency. CONCLUSION: SS therapy relieved excessive loading on the TMJ
      in the TMD OA patients, who showed, via CBCT superimposition, less bone
      resorption in the glenoid fossa.

PMID- 27026212
TI  - The effect of low-intensity pulsed ultrasound on wound healing using scratch
      assay in epithelial cells.
AB  - PURPOSE: Low-intensity pulsed ultrasound (LIPUS) is widely used in medical fields
      because it shortens the time required for biologic wound healing in fracture
      treatment. Also, in dental fields, LIPUS should be effectively employed for
      implant treatment. However, most of the relevant reports have been published on
      its effects on bone formation around implants, and the effects of LIPUS on soft
      tissue healing remain unclear. In the present study, we examined the effects of
      LIPUS on soft tissue healing using gingival epithelial cells. METHODS: Gingival
      epithelial cells were cultured on a dish, followed by LIPUS exposure at a
      frequency of 3MHz for 15min. The cells were counted with a hemocytometer, and a
      scratch assay was conducted by measuring the closing area of the scratch wound
      using a microscope. Following LIPUS exposure, total RNA was collected for
      microarray analysis. In addition, real-time PCR was performed to examine the mRNA
      expression level of integrin alpha6beta4. Furthermore, total protein was
      collected to examine the protein expression level of integrin alpha6beta4 by
      western blotting. RESULTS: The cell count and scratch assay demonstrated that
      LIPUS exposure promoted cell proliferation and scratch-wound closure. Microarray
      analysis demonstrated the increased expression levels of adhesion-related genes,
      including integrin. Real-time PCR analysis demonstrated that LIPUS exposure
      significantly up-regulated the mRNA expression level of integrin alpha6beta4.
      Western blotting showed intense staining of integrin alpha6beta4. CONCLUSION:
      LIPUS exposure promotes wound closure in the scratch assay and up-regulates the
      expression level of integrin alpha6beta4 as compared with the control.

PMID- 27026213
TI  - Mediterranean, invasive, woody species grow larger than their less-invasive
      counterparts under potential global environmental change.
AB  - PREMISE OF THE STUDY: Revealing biological differences between invasive and
      noninvasive species is essential for predicting species' distribution changes
      with global environmental change. While most research has focused on differences
      between invasive and noninvasive species under favorable conditions using
      herbaceous species, invasive woody angiosperms are also of great ecological
      concern. Our study focused on how growth and allocation may change for invasive
      and noninvasive, mediterranean, woody angiosperms under future conditions caused
      by global change, specifically increased nitrogen deposition and drought.
      METHODS: We tested how seedling functional traits differed between invasive and
      noninvasive woody angiosperms under different experimental conditions in a
      greenhouse setting. We compared growth rates and allocation patterns using two
      levels of soil nitrogen and three levels of watering. We also examined trait log
      response ratios to increases in nitrogen and increases in water. Our study
      sampled angiosperm trees and shrubs, incorporating congeneric/confamilial
      relationships through 13 phylogenetically controlled contrasts. KEY RESULTS:
      Three functional traits were highly and positively associated with plant
      invasiveness for most conditions studied: seedling plant mass, leaf area, and
      height. Invasive species also had significantly higher root mass ratios at low
      water regardless of nitrogen input. Invasive and noninvasive species had similar
      log response ratios to increases in nitrogen and watering for studied traits.
      CONCLUSIONS: Mediterranean, woody, invasive species' larger mass, leaf area, and
      early height advantage under elevated nitrogen input and increased root
      production in drought conditions may lead to increased invasion of these species
      with expected global climate change.

PMID- 27026214
TI  - Rapid range expansion of a newly formed allopolyploid weed in the genus Salsola.
AB  - PREMISE OF THE STUDY: Newly formed species (neospecies) can experience a variety
      of demographic fates, ranging from rapid invasive expansion to rapid extinction.
      Here we investigate the fate of the neospecies Salsola ryanii 10 years after its
      initial discovery in the Central Valley of California, USA. This species is an
      allopolyploid derived via hybridization between the invasive species, S.
      australis and S. tragus. METHODS: We conducted a systematic collection of Salsola
      species from 53 sites in California. Species-specific intersimple sequence repeat
      (ISSR) markers were used to determine the species of each individual collected.
      The range of S. ryanii identified in this study was compared to the range in 2002
      to determine how the range has shifted in the decade between surveys. KEY
      RESULTS: In this survey, we identified 15 sites where S. ryanii was present (28%
      of sites), a significant population number increase since 2002. CONCLUSIONS:
      Salsola ryanii has undergone a dramatic population number expansion in the decade
      since it was originally documented. We are not aware of any plant neospecies
      whose range spontaneously experienced such a dramatic expansion. Salsola ryanii
      has every indication of being just as invasive as its highly invasive parents.

PMID- 27026215
TI  - Crop wild relatives of the brinjal eggplant (Solanum melongena): Poorly
      represented in genebanks and many species at risk of extinction.
AB  - PREMISE OF THE STUDY: Crop wild relatives (CWR) provide important traits for
      plant breeding, including pest, pathogen, and abiotic stress resistance.
      Therefore, their conservation and future availability are essential for food
      security. Despite this need, the world's genebanks are currently thought to
      conserve only a small fraction of the total diversity of CWR. METHODS: We define
      the eggplant genepool using the results of recent taxonomic and phylogenetic
      studies. We identify the gaps in germplasm accessions for eggplant (Solanum
      melongena L.) CWR by comparing georeferenced herbarium records and germplasm
      accessions using a gap analysis methodology implementing species distribution
      models (SDM). Preliminary conservation assessments using IUCN criteria were done
      for all species and were combined with the gap analysis to pinpoint where under
      collected and threatened CWR species coincide with high human disturbance and
      occur outside of protected areas. KEY RESULTS: We show that many eggplant CWR are
      poorly represented in genebanks compared to their native ranges. Priority areas
      for future collecting are concentrated in Africa, especially along the Kenya
      Tanzania border. Fourteen species of eggplant CWR are assessed as threatened or
      near-threatened; these are also concentrated in eastern Africa. CONCLUSIONS: The
      knowledge base upon which conservation of wild relative germplasm depends must
      take into account both taxonomic and phylogenetic advances. Beyond traditional
      research focus on close relatives of crops, we emphasize the benefits of defining
      a broad CWR genepool, and the importance of assessing threats to wild species
      when targeting localities for future collection of CWR to improve crop breeding
      in the face of environmental change.

PMID- 27026216
TI  - Gender bias in nineteenth-century England: Evidence from factory children.
AB  - Gender bias against girls in nineteenth-century England has received much
      interest but establishing its existence has proved difficult. We utilise data on
      heights of 16,402 children working in northern textile factories in 1837 to
      examine whether gender bias was evident. Current interpretations argue against
      any difference. Here our comparisons with modern height standards reveal greater
      deprivation for girls than for boys. Discrimination is measured in girls' height
      for-age score (HAZ) falling eight standard errors below boys' at ages 11, 11.5
      and 12 years of age, capturing the very poor performance of factory girls. But
      this result cannot be taken at face value. We query whether modern standards
      require adjustment to account for the later timing of puberty in historical
      populations and develop an alternative. We also test the validity of the age
      data, considering whether parents were more prone to lie about the ages of their
      daughters, and question whether the supply of girls was fundamentally different
      from that of boys. We conclude that neither proposition is justified.
      Disadvantage to girls remains, although its absence amongst younger children
      precludes an indictment of culturally founded gender bias. The height data must
      remain mute on the source of this discrimination but we utilise additional
      information to examine some hypotheses: occupational sorting, differential
      susceptibility to disease, poorer nutrition for girls, disproportionate stunting
      from the effects of nutritional deprivation, and type and amount of work
      undertaken. Of these we suggest that girls had to do arduous physical labour in
      the home alongside their factory work. The only (unsubstantiated) alternative is
      that girls were more likely than boys to be put into factory work below the legal
      age limit. Both represent forms of gender bias.

PMID- 27026218
TI  - In praise of ambidexterity: How a continuum of handedness predicts social
      adjustment.
AB  - This paper estimates the relationship between handedness and social adjustment in
      children. In addition to binary measures of hand preference, we also use a
      continuous measure of relative hand skill. Outcomes at ages 7, 11 and 16 are
      studied. The data used is the British 1958 Birth. Using a partially linear semi
      parametric regression estimator, it is shown that non-right-handedness (as hand
      preference) is associated with poorer social adjustment but this effect weakens
      as individuals age into their teens. The continuous measure of hand skill has a
      non-monotonic effect on social adjustment with poorer social adjustment in the
      tails of the continuum. The results are consistent with a growing body of
      evidence which shows that it is the consistency or degree of laterality (rather
      than direction) that is important for many outcomes.

PMID- 27026217
TI  - Early life height and weight production functions with endogenous energy and
      protein inputs.
AB  - We examine effects of protein and energy intakes on height and weight growth for
      children between 6 and 24 months old in Guatemala and the Philippines. Using
      instrumental variables to control for endogeneity and estimating multiple
      specifications, we find that protein intake plays an important and positive role
      in height and weight growth in the 6-24 month period. Energy from other
      macronutrients, however, does not have a robust relation with these two
      anthropometric measures. Our estimates indicate that in contexts with substantial
      child undernutrition, increases in protein-rich food intake in the first 24
      months can have important growth effects, which previous studies indicate are
      related significantly to a range of outcomes over the life cycle.

PMID- 27026219
TI  - Importance of patient reported outcome measures versus clinical outcomes for
      breast cancer patients evaluation on quality of care.
AB  - INTRODUCTION: Given increasing numbers of breast cancer survivors, there is an
      increased focus on quality of life and quality of care. This study aims to
      investigate whether clinical or patient reported outcomes are most important for
      perceived quality of care by breast cancer patients. METHODS: Overall, 606
      patients aged 18 years or older, who underwent breast cancer surgery 9-18 months
      ago in five hospitals in the Netherlands, were invited to complete an internet
      based questionnaire. Patients were asked to judge a random selection of 24
      patient profiles and choose which of 2 presented patients had received the best
      quality of care, using conjoint analysis. The individual relative importance (RI)
      for each outcome was estimated using Hierarchical Bayes Estimation, and averaged
      over all patients to assess which outcomes were most important. RESULTS: Complete
      data were available for 350 patients (58%). Avoiding severe breast symptoms was
      most important for good quality of care according to patients (RI 23.22 [95%
      Confidence Interval (95% CI) 22.32-24.12]), followed by a 2 year longer disease
      free survival (18.30 [17.38-19.22]). However, the importance differed by age:
      younger patients (<50 years) assigned higher importance to longer disease free
      survival (21.99 [19.52-24.46]) than older patients (65 + years) (15.03 [13.88
      16.18]). CONCLUSION: Avoiding severe breast symptoms rather than 2 year longer
      disease free survival is considered most important in our population of breast
      cancer patients for evaluation of quality of care. These data should thus be
      included in both information provision prior to treatment choices and post
      treatment quality of care evaluation.

PMID- 27026220
TI  - Severe Buruli Ulcer Treated with Minimal Surgical Excision after Prior Biopsy
      Mapping.

PMID- 27026221
TI  - Effect of Royal Jelly Intake on Serum Glucose, Apolipoprotein A-I (ApoA-I),
      Apolipoprotein B (ApoB) and ApoB/ApoA-I Ratios in Patients with Type 2 Diabetes:
      A Randomized, Double-Blind Clinical Trial Study.
AB  - OBJECTIVES: Type 2 diabetes is the most common metabolic disorder worldwide.
      Evidence supports a role for royal jelly (RJ) in reduction of serum glucose and
      lipids in animals and healthy subjects. The purpose of this study was to
      determine the effect of RJ intake on serum glucose, apolipoprotein A-I (ApoA-I),
      apolipoprotein B (ApoB) and ApoB/ApoA-I ratios in patients with type 2 diabetes.
      METHODS: Fifty patients with type 2 diabetes participated in a double-blind,
      placebo-controlled study. The participants were randomly divided into RJ and
      placebo groups and were given doses of 1000 mg royal jelly or placebo 3 times a
      day for 8 weeks, respectively. Weight, height, fasting blood glucose, ApoA-I and
      ApoB were measured at baseline and endpoint. RESULTS: There were no significant
      differences in baseline characteristics and dietary intakes between groups. The
      mean difference in glucose concentrations decreased in the RJ group (-9.4 mg/dL
      vs. 4 mg/dL; p=0.011). The mean difference in ApoA-I concentrations increased in
      the RJ group (34.4 mg/dL vs. -1.08 mg/dL; p=0.013). There was a significant
      decrease in mean difference of ApoB/ApoA-I in the RJ group compared with the
      placebo group (0.008 vs. 0.13; p<0.044), respectively. CONCLUSIONS: These data
      suggest that RJ intake may have desirable effects on serum glucose, Apo-A-I
      concentrations and ApoB/ApoA-I ratios in people with type 2 diabetes.

PMID- 27026222
TI  - Agreement of Point-of-Care Capillary Glycated Hemoglobin Levels with Conventional
      Screening Tests for Diabetes Mellitus in a Canadian First Nations Population.
AB  - OBJECTIVES: 1) How closely do capillary glycated hemoglobin (A1C) levels agree
      with venous A1C levels? 2) How well do venous A1C levels agree with plasma
      glucose for diagnosis of diabetes in this population? METHODS: The Seabird Island
      mobile diabetes clinic screened people not known to have diabetes by using finger
      prick capillary A1C levels with point-of-care analysis according to the
      Siemens/Bayer DCA 2000 system. Clients then went to a clinical laboratory for
      confirmatory testing for venous A1C levels, fasting plasma glucose (FPG) and
      plasma glucose 2 hours after 75 g oral glucose load (2hPG). A reference
      laboratory compared the DCA 2000 and the clinical laboratory's Roche Integra
      800CTS system to the National Glycohemoglobin Standardization Program Diabetes
      Control and Complications Trial (DCCT) reference. RESULTS: 1) In the reference
      laboratory, DCA 2000 and Integra 800CTS both agreed very closely with the DCCT
      standard. In the field, capillary glycated hemoglobin percent (A1C) % was biased,
      underestimating venous A1C % by a mean of 0.19 (p<0.001). The margin of error of
      bias-adjusted capillary A1C % was +/-0.36 for 95% of the time, compared to +/
      0.27 for venous A1C%. 2) By linear regression, we found FPG 7.0 mmol/L and 2hPG
      11.1 mmol/L predicted mean venous A1C levels very close to 6.5%, with no
      significant bias. CONCLUSIONS: Point-of-care capillary A1C did not perform as
      well in the field as in the laboratory, but the bias is correctible, and the
      margin of error is small enough that the test is clinically useful. In this
      population, venous A1C levels >=6.5% agree closely with the FPG and 2hPG
      thresholds to diagnose diabetes; ethnic-specific adjustment of the venous A1C
      threshold is not necessary.

PMID- 27026223
TI  - A Case of Familial Partial Lipodystrophy: From Clinical Phenotype to Genetics.
AB  - We discuss the case of a 56-year-old woman who presented with diabetes from the
      age of 24. The diagnosis of familial partial lipodystrophy was made after the
      discovery of the lamin A/C gene 20 years later. The diagnosis enabled the
      detection of a severe cardiac rhythm disorder with the need for an implantable
      defibrillator. This disease is a rare disorder characterized by an altered body
      fat repartition, cardiac rhythm anomalies and muscular dystrophy.

PMID- 27026224
TI  - Zinc Supplementation Overcomes Effects of Copper on Zinc Status, Carbohydrate
      Metabolism and Some Enzyme Activities in Diabetic and Nondiabetic Rats.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of zinc
      supplementation on zinc status, carbohydrate metabolism and some enzyme
      activities in rats with alloxan-induced diabetes that were fed high-copper feed.
      METHODS: Male albino Wistar rats were randomly divided into 6 groups (n=10). The
      first and fourth groups were nondiabetic and diabetic controls. The second,
      third, fifth and sixth groups were copper, copper + zinc, diabetes + copper and
      diabetes + copper + zinc groups, respectively. Diabetes in the fourth, fifth and
      sixth groups was induced by alloxan. Copper (30 mg/kg feed) as CuSO4 5H2O and
      zinc (231 mg/kg feed) as ZnSO4 7H2O were added to the feed of the animals in the
      copper and zinc groups for 21 days. RESULTS: Copper supplementation caused a
      significant decrease in body weight gain, serum zinc, tissue zinc, serum protein
      concentrations, alkaline phosphatase, lactic dehydrogenase and amylase
      activities. In contrast, it led to an augmentation in creatinine, uric acid and
      transaminases activities in rats with and without diabetes. Zinc supplementation
      in the feed for animals given copper ensured a partial correction of the previous
      parameters. CONCLUSIONS: The study demonstrated the beneficial effects of zinc
      treatment in copper-induced metabolic disturbance in diabetic and nondiabetic
      rats.

PMID- 27026226
TI  - Alice's living croquet theory.

PMID- 27026225
TI  - Mutations of Cytochrome b559 and PsbJ on and near the QC Site in Photosystem II
      Influence the Regulation of Short-Term Light Response and Photosynthetic Growth
      of the Cyanobacterium Synechocystis sp. PCC 6803.
AB  - The characteristic features of two types of short-term light adaptations of the
      photosynthetic apparatus of the cyanobacterium Synechocystis sp. PCC 6803, state
      transition and blue-green light-induced fluorescence quenching, were compared in
      wild-type and cytochrome b559 and PsbJ mutant cells with mutations on and near
      the QC site in photosystem II (PSII). All mutant cells grew photoautotrophically
      and assembled stable PSII. Thermoluminescence emission experiments showed a
      decrease in the stability of the S3QB(-)/S2QB(-) charge pairs in the A16FJ,
      S28Abeta, and V32Fbeta mutant cells. When dark-adapted wild-type and mutant cells
      were illuminated by medium-intensity blue light, the increase in the PSII
      fluorescence yield (indicating a transition to state 1) was more prominent in
      mutant than wild-type cells. Strong blue-light conditions induced a quenching of
      fluorescence corresponding to nonphotochemical fluorescence quenching (NPQ). The
      extension of NPQ decreased significantly in the mutants, and the kinetics
      appeared to be affected. When similar measures were repeated on an orange
      carotenoid protein (OCP)-deficient background, little or no quenching was
      observed, which confirms that the decrease in fluorescence under strong blue
      light corresponded to the OCP-dependent NPQ. Immunoblot results showed that the
      attenuated effect of blue light-induced NPQ in mutant cells was not due to a lack
      of OCP. Photosynthetic growth and biomass production were greater for A16FJ,
      S28Abeta, and V32Fbeta mutant cells than for wild-type cells under normal growth
      conditions. Our results suggest that mutations of cytochrome b559 and PsbJ on and
      near the QC site of PSII may modulate the short-term light response in
      cyanobacteria.

PMID- 27026227
TI  - Central Pseudo-Aneurysm Formation Following Arterial Closure with a StarClose SE
      Device: When a StarClose Doesn't Completely Close.
AB  - BACKGROUND: Vascular closure devices (VCDs) are frequently used for hemostasis
      with endovascular procedures by employing sutures or plug devices (using collagen
      or hydrogel) or through the use of a metal clip made of nickel and titanium, such
      as the StarClose SE device. In comparison to manual compression (MC), VCDs are
      associated with earlier time to discharge and ambulation, improved patient
      comfort, and better cost-effectiveness. CASE REPORT: A 77-year-old man with
      history of ischemic cardiomyopathy with non-ST segment elevation myocardial
      infarction (NSTEMI) underwent diagnostic cardiac catheterization with deployment
      of a StarClose SE vascular closure device for hemostasis. Upon repeat access 4
      days later for coronary intervention, retrograde sheath angiography revealed a
      pseudo-aneurysm emanating from the center of the StarClose clip. CONCLUSIONS: A
      review of the literature shows VCDs to be non-inferior to MC, with an overall
      high success rate. Major and minor complications rates are comparable to those
      with MC, and pseudo-aneurysm is an infrequent complication.

PMID- 27026228
TI  - Monocyte and interferon based therapy for the treatment of ovarian cancer.
AB  - Cytokines and cells of the innate immune system have been shown to be critical
      regulators in the elimination, equilibrium and escape of malignant cells. Despite
      in vitro and in vivo evidence, components of the innate immune system have shown
      limited efficacy in the treatment of ovarian cancer. Intraperitoneal
      immunotherapies are a promising field that has not yet been fully explored in
      ovarian cancer. Cytokine immunotherapy using interferon alpha (IFN-alpha) and
      interferon gamma (IFN-gamma) has predominantly been used intraperitoneally in
      ovarian cancer, with promising results. Early studies also showed that autologous
      monocytes infused into the peritoneum have anti-tumor properties. Combination
      therapies have been shown to be more effective in treating cancer than mono
      therapies. Based on these observations the combination of cell therapy with
      cytokine therapy may provide a unique strategy for the treatment of chemotherapy
      resistant solid cancers.

PMID- 27026229
TI  - Response to post-axitinib treatment in patients with metastatic renal cell
      carcinoma.
AB  - BACKGROUND: Axitinib is a potent inhibitor of the vascular endothelial growth
      factor (VEGF) receptor family with clinical activity in patients with metastatic
      renal cell carcinoma (mRCC). Given this biochemical potency, the clinical
      activity of subsequent treatment with targeted therapies in patients progressing
      on axitinib is of interest. METHODS: Patients with advanced renal cell carcinoma
      of any pathologic subtype treated with at least one cycle (four weeks) of
      axitinib followed by at least one subsequent targeted therapy were investigated
      in a retrospective analysis. Patient characteristics, duration of treatment and
      clinical outcomes were analyzed for axitinib and each subsequent line of therapy
      by Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Twenty-five
      mRCC patients who received at least one approved targeted agent following
      axitinib were identified. Eight percent of patients achieved a partial response
      (one patient each to sunitinib and pazopanib) and 42 % had a best response of
      stable disease to the first therapy after axitinib. The estimated median duration
      of therapy was 4.4 months (range, 0.2-27.5+). Twelve patients received a second
      post-axitinib targeted therapy. Six out of 11 evaluable patients (55 %) had a
      best response of SD. The estimated median duration of treatment was 4.8 months
      (range, 0.7-19.1+). CONCLUSION: Objective responses and stable disease is
      observed to post-axitinib targeted therapies and prospective studies are needed
      for validating role of predictive biomarkers.

PMID- 27026230
TI  - GAB2 promotes cell proliferation by activating the ERK signaling pathway in
      hepatocellular carcinoma.
AB  - Grb2-associated binding protein 2 (GAB2), a key member of the family of Gab
      scaffolding adaptors, is important in the phospoinositide3-kinase (PI3K) and
      extracellular signal-regulated kinase (ERK) signaling pathways, and is closely
      associated with cell proliferation, cell transformation, and tumor progression.
      But its role in hepatocellular carcinoma (HCC) is still unknown. In this study,
      we investigated the expression of GAB2 and its potential clinical and biological
      significances in HCC. Western bolt and immunohistochemistrical analyses revealed
      that GAB2 was obviously upregulated in HCC tissues. Meanwhile, GAB2 was
      significantly associated with histological grade, tumor size, and the
      proliferation marker Ki-67 through our further analysis. The Kaplan-Meier
      survival curves also showed that increased GAB2 expression was directly
      correlated with poor prognosis in HCC patients and served as an independent
      prognostic marker of overall survival. Moreover, serum starvation-refeeding, RNA
      interference, CCK-8, EDU, colony formation, and flow-cytometry analyses were all
      performed with the purpose of investigating GAB2's regulation of HCC cell
      proliferation. Our results indicated that GAB2 progressively accumulated when
      cells entered into S phase. Consistently, cell proliferation was distinctly
      hindered by small interfering RNA. More interestingly, we discovered that GAB2
      promoted cell proliferation by enhancing ERK signaling and GAB2-induced cell
      proliferation was inhibited by the inhibition of ERK activation. Finally, GAB2
      was verified to be able to confer doxorubicin resistance in HCC cells. In
      summary, these data demonstrated that GAB2 might promote HCC cell proliferation
      by enhancing ERK signaling, and all above findings provided a potential
      therapeutic strategy for the treatment of HCC.

PMID- 27026231
TI  - The milk delivery chain and presence of Brucella spp. antibodies in bulk milk in
      Uganda.
AB  - This study examined the influence of informal milk delivery chains on the risk of
      human exposure to Brucella spp. through milk consumption in two regions of Uganda
      (Gulu and Soroti Districts). The work involved describing milk delivery chains,
      investigating brucellosis awareness amongst milk deliverers and determining the
      presence of Brucella spp. antibodies in cattle milk on delivery to primary
      collection points (boiling points and dairies). Milk samples (n = 331) were
      collected from deliverers at primary collection points and from street vendors at
      point of sale and analysed using indirect enzyme-linked immunosorbent assay (I
      ELISA). A written questionnaire was used to collect data from deliverers (n =
      279) on their milk delivery chains and their brucellosis awareness. The most
      common delivery points in Gulu District were small dairies and in Soroti District
      boiling points. The presence of Brucella spp. antibodies in milk samples was
      higher in Soroti (40 %) than in Gulu (11 %) (P < 0.0001). There are possible
      public health risk consequences of this finding as 42 % of deliverers in Soroti
      District reported drinking raw milk, compared with 15 % in Gulu District (P <
      0.0001). Awareness of brucellosis was low, with 70 % of all milk deliverers
      reporting not having heard of the disease or the bacterium. Application of
      quality controls for milk (colour and odour) along the delivery chain varied
      depending upon supply and demand. This study provides evidence of the diversity
      of informal milk markets in low-income countries and of the potential public
      health risks of consuming unpasteurised milk. These results can be useful to
      those planning interventions to reduce brucellosis. 

PMID- 27026232
TI  - Effects of crude glycerin from waste vegetable oil supplementation on feed
      intake, ruminal fermentation characteristics, and nitrogen utilization of goats.
AB  - This experiment was evaluation of the effects of increasing concentrations of
      crude glycerin from waste vegetable oil (CGWVO) in diets on feed intake,
      digestibility, ruminal fermentation characteristics, and nitrogen balance of
      goats. Four crossbred male (Thai Native * Anglo Nubian) goats, with an average
      initial body weight (BW) of 31.5 +/- 1.90 kg, were randomly assigned according to
      a 4 * 4 Latin square design. The dietary treatments contained 0, 2, 4, and 6 % of
      dietary dry matter (DM) of CGWVO. Based on this experiment, there were
      significantly different (P > 0.05) among treatment groups regarding DM intake and
      digestion coefficients of nutrients (DM, OM, CP, EE, NDF, and ADF), which goats
      receiving 6 % of CGWVO had lower daily DMI and nutrient intake than those fed on
      0, 2, and 4 % of CGWVO. Ruminal pH, NH3-N, and blood urea nitrogen (BUN)
      concentration were unchanged by dietary treatments, except that for 6 % of CGWVO
      supplementation, NH3-N, and BUN were lower (P < 0.05) than for the diets 0 % of
      CGWVO, while the differences between the diets 0, 2, and 4 % of CGWVO were not
      significant. The amounts of N absorption and retention were similar among
      treatments, except that for 6 % of CGWVO which N absorption was lower (P < 0.05)
      than among treatments while the difference between the diets 0, 2, and 4 % of
      CGWVO were not significant. Based on this study, CGWVO levels up to 4 % in total
      mixed ration could be efficiently utilized for goats. This study was a good
      approach in exploiting the use of biodiesel production from waste vegetable oil
      for goat production. 

PMID- 27026233
TI  - Neurotuberculosis in cattle in southern Brazil.
AB  - Tuberculosis in cattle is a chronic infectious-contagious disease characterized
      by the development of nodular lesions (granulomas) in mainly the lungs and
      regional lymph nodes. It is caused by Mycobacterium tuberculosis complex, an acid
      fast bacillus (AFB). Tuberculosis in the central nervous system is a rare
      condition in cattle. Herein, we describe the clinical and pathological findings
      of six neurotuberculosis cases in cattle diagnosed in Southern Brazil. The
      average age of the cattle affected was 12 months, and they varied in breed and
      sex. The clinical history ranged from 5 to 30 days and was characterized by motor
      incoordination, opisthotonus, blindness, and progression to recumbency. The
      cattle were euthanized, and grossly, the leptomeninges at the basilar brain
      showed marked and diffuse expansion, with nodular yellowish lesions ranging in
      size. On microscopic examination, there were multifocal granulomas located mainly
      in the meninges, though sometimes extending to adjacent neuropil or existing as
      isolated granulomas in neuropil. AFBs were observed in the cytoplasm of
      epithelioid macrophages and multinucleated giant cells through Ziehl-Neelsen
      histochemical staining and identified as Mycobacterium sp. through
      immunohistochemistry. 

PMID- 27026234
TI  - Protein requirements of finishing paca (Cuniculus paca).
AB  - We conducted a nitrogen balance digestion trial to determine the crude protein
      requirements of paca (Cuniculus paca) during the last growth phase. In a 4 * 4
      Latin square design, four young captive male pacas, aged 5 months, were fed four
      isoenergetic diets containing four different levels of nitrogen (N) (11.3, 16.6,
      21.4, and 26.6 g N/kg of dry matter). After 15 days of adaptation, we collected
      all feces and urine for five consecutive days. By regression analysis between N
      intake and N in feces and urine, the metabolic fecal nitrogen (MFN = 4.2 g/kg of
      dry matter intake) and daily endogenous urinary N (EUN = 91.6 mg/kg(0.75)) were
      determined. Likewise, by regression analyses between nitrogen intake and nitrogen
      retention [NR = N intake-(fecal N + urine N)], we estimated the daily requirement
      of 280.5 mg N/kg(0.75). Therefore, a minimum of 55 g crude protein per kilogram
      dry matter and 13 MJ/kg of digestible energy are required by finishing paca on
      unrestricted diets. Such values are similar to those of other wild frugivores and
      below those of growing rabbits. The data confirm that farmers overfeed protein,
      and similar growth can be more economically achieved on lower protein diets. 

PMID- 27026235
TI  - It's Time for the Genetic Counseling Profession to Embrace Social Media.
AB  - Social Media is a powerful and emerging method of communication that is becoming
      increasingly popular in genetic counseling and other health care communities.
      Despite its multiple benefits, the Social Media revolution has been met with some
      resistance in the healthcare setting. Herein, we will describe the potential
      benefits of Social Media for the genetic counseling profession specifically and
      explore ways in which any risks can be mitigated and barriers overcome to ensure
      responsible Social Media use by the profession.

PMID- 27026236
TI  - Screen all for depression.

PMID- 27026237
TI  - The influence of life history characteristics on flea (Siphonaptera) species
      distribution models.
AB  - BACKGROUND: Ectoparasites exhibit pronounced variation in life history
      characteristics such as time spent on the host and host range. Since contemporary
      species distribution (SD) modelling does not account for differences in life
      history, the accuracy of predictions of current and future species' ranges could
      differ significantly between life history groups. RESULTS: SD model performance
      was compared between 21 flea species that differ in microhabitat preferences and
      level of host specificity. Distribution models generally performed well, with no
      significant differences in model performance based on either microhabitat
      preferences or host specificity. However, the relative importance of predictor
      variables was significantly related to host specificity, with the distribution of
      host-opportunistic fleas strongly limited by thermal conditions and host-specific
      fleas more associated with conditions that restrict their hosts' distribution.
      The importance of temperature was even more pronounced when considering
      microhabitat preference, with the distribution of fur fleas being strongly
      limited by thermal conditions and nest fleas more associated with variables that
      affect microclimatic conditions in the host nest. CONCLUSIONS: Contemporary SD
      modelling, that includes climate and landscape variables, is a valuable tool to
      study the biogeography and future distributions of fleas and other parasites
      taxa. However, consideration of life history characteristics is cautioned as
      species may be differentially sensitive to environmental conditions.

PMID- 27026238
TI  - Streptococcus pneumoniae carriage among healthy and sick pediatric patients
      before the generalized implementation of the 13-valent pneumococcal vaccine in
      Morocco from 2010 to 2011.
AB  - Nasopharyngeal carriage studies provide insights into the local prevalence of
      circulating pneumococcal serotypes. These data are critical to vaccination
      monitoring, as they allow for the prediction and assessment of impact. Very
      little data are available on the carriage of pneumococcal serotypes in Morocco.
      Here, we describe the prevalence of Streptococcus pneumoniae carriage and
      serotype distribution among 697 pediatric patients with ages ranging from 2 to 59
      months who were admitted to a Moroccan hospital with severe pneumonia, as well as
      195 healthy infants and young children who were recruited at a vaccination
      clinic. Carriage rates were 40.5% (79/195) for healthy children and 22.8%
      (159/697) for sick children. The most commonly observed circulating serotypes
      included 6A, 6B and 19F, all of which are included in the current 13-valent anti
      pneumococcal conjugate vaccine that was recently introduced in Morocco.
      Monitoring of circulating serotypes remains necessary after vaccine introduction
      to assess whether serotype replacement is occurring.

PMID- 27026239
TI  - Tuberculosis control in Sindh, Pakistan: Critical analysis of its implementation.
AB  - Tuberculosis (TB) remains one of the main health problems despite preventive and
      control measures that have been taken in the past few decades. It is responsible
      for almost 8.8 million cases and 1.4 million deaths around the world. Lack of
      access to TB services is a barrier for empowering TB patients. In a country like
      Pakistan, controlling TB has become a challenge because of the lack of private
      sector involvement in a National Tuberculosis Control Program (NTP). Therefore,
      collaboration is needed between public, private and government sectors in
      treating TB as well as in improving the quality of the health care system.

PMID- 27026240
TI  - Low prevalence, low immunization and low adherence to full hepatitis B vaccine
      scheme and high-risk behaviors among crack cocaine users in central Brazil.
AB  - Crack cocaine users represent a target group for hepatitis B vaccination. We
      evaluate the HBV epidemiology, immunization status and compliance with a super
      accelerated vaccination schedule among in-treatment crack cocaine users in
      central Brazil. Six hundred in-treatment crack cocaine users were interviewed,
      and serum samples were tested for HBV markers. A super-accelerated vaccination
      schedule of HBV vaccine was offered to all susceptible crack cocaine users. In
      total, 7.0% of those tested had at least one positive marker of HBV exposure.
      Age, use of crack cocaine through improvised pipe, exchange of sex for
      money/drugs and previous sexually transmitted infections (STIs) were predictors
      of HBV exposure. One hundred six (17.7%) individuals showed a serological profile
      of hepatitis B vaccination. Of these, 54.7% were less than 25 years old, and only
      13% of individuals were more than 35 years old. Although 91.8% of crack users
      accepted the first vaccine dose, only 21.7% received all three doses. Of the 23
      crack cocaine users who agreed to have their vaccine response evaluated, 78.3%
      developed protective anti-HBs titers. Premature termination of treatment was the
      most common reason for not receiving the full vaccine series. Despite the low
      prevalence of HBV exposure among in-treatment crack cocaine users in central
      Brazil, the low rate of immunization and the high frequency of high-risk
      behaviors highlight the potential for crack users to acquire and disseminate this
      infection and therefore maintain the viral reservoir. Health practitioners need
      to keep this in mind, taking advantage of all opportunities to access this
      population and vaccinate against HBV.

PMID- 27026241
TI  - Oral administration of synthetic selenium nanoparticles induced robust Th1
      cytokine pattern after HBs antigen vaccination in mouse model.
AB  - : Hepatitis B virus (HBV) infection is known as a life-threatening liver
      infection and leads to chronic liver disease if left untreated. Nevertheless, the
      prevalence of HBV infection has been reduced by an approved vaccination approach
      using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV
      vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a
      strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg
      vaccination; however, the present vaccine does not induce a prophylactic immune
      response in some groups. The main aim of the present study was to induce a Th1
      cytokine pattern and stimulate an immune response after HBsAg vaccination.
      Experimental mice were fed selenium nanoparticles (SeNPs) and were later
      immunized with 5MUg of Hepatitis B Vaccine. After a period of 30 days, the
      experimental animals were given two booster doses of SeNPs during their
      vaccination course. Group one, i.e., the control vaccine group, was only
      administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were
      daily fed different doses of SeNPs (100MUg and 200MUg, respectively) via gavage.
      Group four was considered the control group and was only given phosphate buffered
      saline (PBS). Lymphocyte proliferation, IFN-gamma and IL-4 levels, total antibody
      and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked
      Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen
      vaccine affected the lymphocyte proliferation; moreover, the total antibody
      responses also increased the IFN-gamma level and induced a Th1 response.
      CONCLUSIONS: The present study proposed that the administration of SeNPs with a
      conventional HBs antigen vaccine induces a better immune response with a Th1
      bias.

PMID- 27026243
TI  - Cranial fixation plates in cerebral magnetic resonance imaging: a 3 and 7 Tesla
      in vivo image quality study.
AB  - OBJECTIVE: This study assesses and quantifies impairment of postoperative
      magnetic resonance imaging (MRI) at 7 Tesla (T) after implantation of titanium
      cranial fixation plates (CFPs) for neurosurgical bone flap fixation. MATERIALS
      AND METHODS: The study group comprised five patients who were intra-individually
      examined with 3 and 7 T MRI preoperatively and postoperatively (within 72 h/3
      months) after implantation of CFPs. Acquired sequences included T1-weighted
      magnetization-prepared rapid-acquisition gradient-echo (MPRAGE), T2-weighted
      turbo-spin-echo (TSE) imaging, and susceptibility-weighted imaging (SWI). Two
      experienced neurosurgeons and a neuroradiologist rated image quality and the
      presence of artifacts in consensus reading. RESULTS: Minor artifacts occurred
      around the CFPs in MPRAGE and T2 TSE at both field strengths, with no significant
      differences between 3 and 7 T. In SWI, artifacts were accentuated in the early
      postoperative scans at both field strengths due to intracranial air and
      hemorrhagic remnants. After resorption, the brain tissue directly adjacent to
      skull bone could still be assessed. Image quality after 3 months was equal to the
      preoperative examinations at 3 and 7 T. CONCLUSION: Image quality after CFP
      implantation was not significantly impaired in 7 T MRI, and artifacts were
      comparable to those in 3 T MRI.

PMID- 27026242
TI  - Coffee consumption, obesity and type 2 diabetes: a mini-review.
AB  - PURPOSE: The effects of regular coffee intake on weight gain and development of
      diabetes are reviewed. The pathophysiology of obesity and type 2 diabetes as well
      as the necessity of preventive options based on the increasing prevalence of
      these two disorders worldwide is briefly discussed. The relationship between
      weight gain and development of diabetes is also presented. The two major
      constituents in the brewed coffee, chlorogenic acids and caffeine, are
      responsible for many of the beneficial effects suggested by numerous
      epidemiological studies of coffee consumption and the development of diabetes.
      METHODS: A wide search of various databases, such as PubMed and Google Scholar,
      preceded the writing of this manuscript, focusing on key words that are part of
      the title. It was selected mainly review papers from in vivo, ex vivo, in vitro
      experimental studies in animals and human tissues as well as wide population
      based epidemiological studies in the last 10 years. CONCLUSION: As of today,
      there are mounting evidences of the reduced risk of developing type 2 diabetes by
      regular coffee drinkers of 3-4 cups a day. The effects are likely due to the
      presence of chlorogenic acids and caffeine, the two constituents of coffee in
      higher concentration after the roasting process.

PMID- 27026244
TI  - Automated assessment of thigh composition using machine learning for Dixon
      magnetic resonance images.
AB  - OBJECTIVES: To develop and validate a machine learning based automated
      segmentation method that jointly analyzes the four contrasts provided by Dixon
      MRI technique for improved thigh composition segmentation accuracy. MATERIALS AND
      METHODS: The automatic detection of body composition is formulized as a three
      class classification issue. Each image voxel in the training dataset is assigned
      with a correct label. A voxel classifier is trained and subsequently used to
      predict unseen data. Morphological operations are finally applied to generate
      volumetric segmented images for different structures. We applied this algorithm
      on datasets of (1) four contrast images, (2) water and fat images, and (3)
      unsuppressed images acquired from 190 subjects. RESULTS: The proposed method
      using four contrasts achieved most accurate and robust segmentation compared to
      the use of combined fat and water images and the use of unsuppressed image,
      average Dice coefficients of 0.94 +/- 0.03, 0.96 +/- 0.03, 0.80 +/- 0.03, and
      0.97 +/- 0.01 has been achieved to bone region, subcutaneous adipose tissue
      (SAT), inter-muscular adipose tissue (IMAT), and muscle respectively. CONCLUSION:
      Our proposed method based on machine learning produces accurate tissue
      quantification and showed an effective use of large information provided by the
      four contrast images from Dixon MRI.

PMID- 27026245
TI  - Technical feasibility of integrating 7 T anatomical MRI in image-guided
      radiotherapy of glioblastoma: a preparatory study.
AB  - OBJECTIVES: The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently
      shown great potential for high-resolution soft-tissue neuroimaging and
      visualization of microvascularization in glioblastoma (GBM). We have designed a
      clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For
      this aim we performed a preparatory study to investigate the technical
      feasibility of incorporating 7 T MR images into the neurosurgical navigation and
      radiotherapy treatment planning (RTP) systems via qualitative and quantitative
      assessment of the image quality. MATERIALS AND METHODS: The MR images were
      acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32
      channel head coil. The 7 T MRI pulse sequences included magnetization-prepared
      two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and
      gradient echo sequences (GRE). A pilot study with three healthy volunteers and an
      anthropomorphic 3D phantom was used to assess image quality and geometrical image
      accuracy. RESULTS: The MRI scans were well tolerated by the volunteers.
      Susceptibility artefacts were observed in both the cortex and subcortical white
      matter at close proximity to air-tissue interfaces. Regional loss of signal and
      contrast could be minimized by the use of dielectric pads. Image transfer and
      processing did not degrade image quality. The system-related spatial uncertainty
      of geometrical distortion-corrected MP2RAGE pulse sequences was <=2 mm.
      CONCLUSION: Integration of high-quality and geometrically-reliable 7 T MR images
      into neurosurgical navigation and RTP software is technically feasible and safe.

PMID- 27026246
TI  - Molar incisor hypomineralisation (MIH): correlation with dental caries and dental
      fear.
AB  - AIM: This cross-sectional study was to investigate correlations between molar
      incisor hypomineralisation (MIH), dental caries and child dental fear. MATERIALS
      AND METHODS: The subjects in the study were representative samples of 8 and 14
      year old children from three Greek cities (total N = 2335). Dental examinations
      were performed by one calibrated examiner in classrooms, after the children had
      brushed their teeth, using an intraoral mirror and artificial room light
      supplemented by a penlight. All the children completed the children's fear survey
      schedule-dental subscale (CFSS-DS) questionnaire. MIH scores were recorded using
      EAPD criteria and dental caries experience by DMFS/dmfs index. Data were analysed
      with the Chi-squared (chi (2)), Mann-Whitney and Spearman's rank correlation
      coefficient tests. RESULTS: The mean DMFS in children with MIH (8-year olds: 1.60
      +/- 2.01, 14-year olds: 4.60 +/- 4.41) was statistically significantly higher
      than children without MIH (8-year olds: 1.01 +/- 1.78, 14-year olds: 3.46 +/-
      4.28) (p < 0.001 for both age groups). Children with severe MIH had statistically
      significantly higher mean DMFS scores than children with mild or no MIH (p <
      0.001), while the dmfs of the 8 year olds were unrelated to their MIH status (p =
      0.332). Caries experience was associated with the MIH status of the first
      permanent molars in both age groups (p < 0.001). The mean CFSS-DS scores did not
      differ significantly between the groups of children without (26.2 +/- 9.9) or
      with MIH (26.5 +/- 9.6) (p = 0.339), regardless of MIH severity. CONCLUSIONS: A
      positive association between MIH and dental caries was confirmed and a lack of
      association found between MIH and dental fear in Greek children.

PMID- 27026247
TI  - The Impact of Reduced Pulse Oximetry Use on Alarm Frequency.
AB  - BACKGROUND: Concerns about alarm fatigue prompted The Joint Commission to issue a
      Sentinel Event Alert urging hospitals to minimize alarms. We previously conducted
      a quality improvement project on a single unit that reduced time on continuous
      pulse oximetry, a common source of physiologic monitor alarms, for patients with
      wheezing (ie, asthma and bronchiolitis, wheezing-associated respiratory
      infections). OBJECTIVE: To study the impact of our improvement work on overall
      physiologic monitor alarm frequency for these patients. METHODS: This was a
      retrospective cohort study at a freestanding children's hospital over an 8-week
      period. We compared alarm count, including respiratory, cardiac, and pulse
      oximetry alarms, for patients admitted to the intervention unit with the alarm
      count for similar patients on a control unit by using the Wilcoxon rank sum test.
      We used negative binomial regression to evaluate differences in alarm count
      between the units, adjusting for age, medical comorbidity, and length of stay.
      RESULTS: There were 101 patients on the intervention unit and 46 patients on the
      control unit. The percentage of patients with medical comorbidities was
      significantly higher on the intervention unit (P=.01). Median alarm count per day
      for patients on the intervention unit was lower; however, this difference was not
      statistically significant (71 vs 76 alarms per patient-day, P=.29). The
      multivariable model estimated a nonsignificant 6.4-count decrease in alarms for
      patients on the intervention unit. CONCLUSIONS: Reducing continuous pulse
      oximetry use alone may not make substantial reductions in overall alarm counts.
      Even on our intervention unit, alarm burden remained quite high.

PMID- 27026248
TI  - Blastic Plasmacytoid Dendritic Cell Neoplasm: From Origin of the Cell to Targeted
      Therapies.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological
      malignancy with an aggressive clinical course. It is grouped with acute myeloid
      leukemia-related precursor neoplasms in the 2008 World Health Organization
      classification. Most patients with BPDCN have skin lesions at diagnosis and
      subsequent or simultaneous involvement of the bone marrow, peripheral blood, and
      lymph nodes. Patients usually respond to initial chemotherapy but often relapse.
      Stem cell transplantation may improve survival. This neoplasm is derived from
      precursors of plasmacytoid dendritic cells and is characterized by the
      coexpression of the immunophenotypic markers CD4, CD56, CD123, blood dendritic
      cell antigen-2, blood dendritic cell antigen-4, CD2AP, and lineage(-). Atypical
      immunophenotype expression may be present, making diagnosis difficult. BPDCN is
      often associated with a complex karyotype, frequent deletions of tumor suppressor
      genes, and mutations affecting either the DNA methylation or chromatin remodeling
      pathways. A better understanding of the etiology and pathophysiology of this
      neoplasm could open the way to new therapies targeting specific signaling
      pathways or involving epigenetics.

PMID- 27026249
TI  - Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute
      Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell
      Transplant.
AB  - Allogeneic stem cell transplantation (allo-SCT) is a potentially curative
      treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome
      (MDS). For patients with relapsed disease after transplantation, intensive
      chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may
      result in a durable response in some patients. High-intensity chemotherapy and
      less aggressive therapy with hypomethylating agents (HAs) with and without DLI
      are often used for relapse after allo-SCT. Here we compared the treatment
      outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after
      allo-SCT. Patients who had received a second SCT within 90 days of the relapse
      date were excluded. The primary endpoints were overall response rate (ORR) and
      overall survival (OS). Secondary endpoints were complete remission (CR) rate and
      progression-free survival (PFS). One hundred patients were included: 73 patients
      received chemotherapy and 27 patients received an HA. Fifty-six percent of
      patients in the chemotherapy group and 33% of patients in the HA group received
      at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher
      ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002).
      The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P =
      .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over
      HAs was maintained in all treatment outcomes after controlling for the use of
      DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR,
      68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our
      hands, with limited numbers, the use of more conventional salvage chemotherapy,
      with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT
      is associated with better outcomes than nonchemotherapy (HA) options.

PMID- 27026250
TI  - Lethal poisoning with Gelsemium elegans in Guizhou, China.

PMID- 27026251
TI  - Disclosing large scale adverse events in the US Veterans Health Administration:
      lessons from media responses.
AB  - OBJECTIVES: We examined print, broadcast and social media reports about health
      care systems' disclosures of large scale adverse events to develop future
      effective messaging. STUDY DESIGN: Directed content analysis. METHODS: We
      systematically searched four communication databases, YouTube and Really Simple
      Syndication (RSS) feeds relating to six disclosures of lapses in infection
      control practices in the Department of Veterans Affairs occurring between 2009
      and 2012. We assessed these with a coding frame derived from effective crisis and
      risk communication models. RESULTS: We identified 148 unique media reports. Some
      components of effective communication (discussion of cause, reassurance, self
      efficacy) were more present than others (apology, lessons learned). Media about
      'promoting secrecy' and 'slow response' appeared in reports when time from event
      discovery to patient notification was over 75 days. Elected officials' quotes (n
      = 115) were often negative (83%). Hospital officials' comments (n = 165) were
      predominantly neutral (92%), and focused on information sharing. CONCLUSIONS:
      Health care systems should work to ensure that they develop clear messages
      focused on what is not well covered by the media, including authentic apologies,
      remedial actions taken, and shorten the timeframe between event identification
      and disclosure to patients.

PMID- 27026252
TI  - Pertussis vaccination for healthcare workers: staff attitudes and perceptions
      associated with high coverage vaccination programmes in England.

PMID- 27026254
TI  - Marine microbiology: Microbiome 'coral'ations.

PMID- 27026253
TI  - Fuelling the future: microbial engineering for the production of sustainable
      biofuels.
AB  - Global climate change linked to the accumulation of greenhouse gases has caused
      concerns regarding the use of fossil fuels as the major energy source. To
      mitigate climate change while keeping energy supply sustainable, one solution is
      to rely on the ability of microorganisms to use renewable resources for biofuel
      synthesis. In this Review, we discuss how microorganisms can be explored for the
      production of next-generation biofuels, based on the ability of bacteria and
      fungi to use lignocellulose; through direct CO2 conversion by microalgae; using
      lithoautotrophs driven by solar electricity; or through the capacity of
      microorganisms to use methane generated from landfill. Furthermore, we discuss
      how to direct these substrates to the biosynthetic pathways of various fuel
      compounds and how to optimize biofuel production by engineering fuel pathways and
      central metabolism. 

PMID- 27026256
TI  - Microbiome: Baby steps towards the microbiome.

PMID- 27026257
TI  - Value of Virtual Touch Quantification Elastography for Assessing Liver Congestion
      in Patients With Heart Failure.
AB  - BACKGROUND: Heart failure (HF) causes organ congestion, which is thought to
      increase organ stiffness. The virtual touch quantification (VTQ) method can be
      used to assess liver stiffness in patients with chronic liver diseases. This
      study aimed to measure liver and kidney stiffness using VTQ and to determine its
      value for assessing organ congestion in patients with HF. METHODS AND RESULTS:
      This study included 10 normal subjects and 38 HF patients (age 52.3+/-16.7 years,
      left ventricular ejection fraction 27.0+/-9.4%, plasma B-type natriuretic peptide
      [BNP] 1,297.3+/-1,155.1 pg/ml). We investigated the relationships between
      clinical characteristics and hemodynamics and liver and kidney stiffness, and
      assessed the effects of medical treatment on these measurements. Liver stiffness
      was significantly higher in HF patients (1.17+/-0.13 m/s vs. 2.03+/-0.91 m/s,
      P=0.004) compared with normal subjects, but kidney stiffness was similar in both
      groups. Central venous pressure (CVP) (P=0.021) and BNP (P=0.025) were
      independent predictive factors for increased liver stiffness in HF patients.
      Liver stiffness decreased significantly from 2.37+/-1.09 to 1.27+/-0.33 m/s
      (P<0.001) after treatment. Changes in liver stiffness in HF patients
      significantly correlated with changes in CVP (R=0.636, P=0.014) and cardiac index
      (R=-0.557, P=0.039) according to univariate analysis, and with changes in CVP in
      multivariate analysis. CONCLUSIONS: Liver stiffness measured by noninvasive VTQ
      methods can be used to assess liver congestion and therapeutic effects in
      patients with HF. (Circ J 2016; 80: 1187-1195).

PMID- 27026255
TI  - Lipopolysaccharide transport and assembly at the outer membrane: the PEZ model.
AB  - Gram-negative bacteria have a double-membrane cellular envelope that enables them
      to colonize harsh environments and prevents the entry of many clinically
      available antibiotics. A main component of most outer membranes is
      lipopolysaccharide (LPS), a glycolipid containing several fatty acyl chains and
      up to hundreds of sugars that is synthesized in the cytoplasm. In the past two
      decades, the proteins that are responsible for transporting LPS across the
      cellular envelope and assembling it at the cell surface in Escherichia coli have
      been identified, but it remains unclear how they function. In this Review, we
      discuss recent advances in this area and present a model that explains how energy
      from the cytoplasm is used to power LPS transport across the cellular envelope to
      the cell surface.

PMID- 27026258
TI  - Estimating Left Ventricular Relaxation and Filling Pressure Using Speckle
      Tracking Strain.

PMID- 27026259
TI  - Bioresorbable Scaffold - Taking the Edge Off?

PMID- 27026260
TI  - Does hyperbaric oxygen therapy reduce the effects of ischemia on colonic
      anastomosis in laparoscopic colon resection?
AB  - BACKGROUND: An increase in intra-abdominal pressure causes a decrease in the
      splanchnic blood flow and the intramucosal pH of the bowel, as well as increasing
      the risk of ischemia in the colon. The aim of the present study is to evaluate
      the effect of hyperbaric oxygen therapy (HBOT) on the ischemia caused by
      laparoscopy in colonic anastomosis in an experimental model of laparoscopic
      colonic surgery. MATERIALS AND METHODS: We divided 30 male Wistar albino rats
      into three groups: Group A was the control (open colon anastomosis); Group B
      received LCA (laparoscopic colon anastomosis); while Group C received both LCA
      and HBOT. Each group contained ten animals. We placed Group C (LCA and HBOT) in
      an experimental hyperbaric chamber into which we administered pure oxygen at 2.1
      atmospheres absolute 100% oxygen for 60 min for ten consecutive days. RESULTS:
      The anastomotic bursting pressure value was found to be higher in the open
      surgery group (226 +/- 8.8) (Group A). The result for Group C (213 +/- 27), which
      received HBOT, was better than that for Group B (197 +/- 27). However, there was
      no statistically significant difference between Group B and Group C. Group A
      showed better healing than the other groups, while significant differences in the
      fibroblast proliferation scores were found between Groups A and B. In terms of
      tissue hydroxyproline levels, a significant difference was found between Groups A
      and B and between Groups A and C, but not between Groups B and C. CONCLUSIONS:
      HBOT increases the oxygen level in the injured tissue. Although HBOT might offer
      several advantages, it had only a limited effect on the healing of colonic
      anastomosis in rats with increased intra-abdominal pressure in our study. KEY
      WORDS: Anastomosis, Colon, Hyperbaric Oxygen Treatment, Oxidative Stress.

PMID- 27026261
TI  - Silver(I)-Mediated Phosphorylation/Cyclization Cascade of N-Cyanamide Alkenes for
      Divergent Access to Quinazolinones and Dihydroisoquinolinones.
AB  - A silver(I)-mediated phosphorylation/cyclization radical cascade of N-cyanamide
      alkenes has been developed. The addition of in situ generated phosphorus radical
      to N-cyanamide alkenes triggers the cascade, resulting in late-stage cyclization
      toward divergent access to 4-quinazolinones and dihydroisoquinolinones. Both
      terminal and internal N-cyanamide alkenes are applicable in this protocol, and
      the cyclizations are consistent with Baldwin's rule. 

PMID- 27026262
TI  - Impacts of diurnal variation of ultraviolet-B and photosynthetically active
      radiation on phycobiliproteins of the hot-spring cyanobacterium Nostoc sp. strain
      HKAR-2.
AB  - The effects of diurnal variation of photosynthetically active radiation (PAR; 400
      700 nm) and ultraviolet-B (UV-B; 280-315 nm) radiation on phycobiliproteins
      (PBPs) and photosynthetic pigments (PP) have been studied in the hot-spring
      cyanobacterium Nostoc sp. strain HKAR-2. The variations in PBPs and PP were
      monitored by alternating light and dark under PAR, UV-B, and PAR + UV-B
      radiations over a period of 25 h. There was a decline in the amount of Chl a and
      PBPs during light periods of UV-B and PAR + UV-B and an increase during dark
      periods showing a circadian rhythm by destruction and resynthesis of pigment
      protein complex. However, a marked induction in carotenoids was recorded during
      light periods of the same radiations. Moreover, the ratio of Chl a/PE and Chl
      a/PC was increased in dark periods showing the resynthesis of bleached Chl a. The
      wavelength shift in emission fluorescence of PBPs toward shorter wavelengths
      further indicated the bleaching and destruction of PBPs during light periods.
      Oxidative damage upon exposure to PAR, UV-B, and PAR + UV-B was alleviated by
      induction of antioxidative enzymes such as superoxide dismutase (SOD), catalase
      (CAT), and ascorbate peroxidase (APX). The studied cyanobacterium exhibits a
      significant increase in the activities of SOD, CAT, and APX upon exposure to UV-B
      and PAR + UV-B radiations. The results indicate that pigment-protein composition
      of Nostoc sp. stain HKAR-2 was significantly altered during diurnal variation of
      light/radiation, which might play an important role in optimization for their
      productivity in a particular cyanobacterium.

PMID- 27026263
TI  - A developmentally regulated switch from stem cells to dedifferentiation for limb
      muscle regeneration in newts.
AB  - The newt, a urodele amphibian, is able to repeatedly regenerate its limbs
      throughout its lifespan, whereas other amphibians deteriorate or lose their
      ability to regenerate limbs after metamorphosis. It remains to be determined
      whether such an exceptional ability of the newt is either attributed to a
      strategy, which controls regeneration in larvae, or on a novel one invented by
      the newt after metamorphosis. Here we report that the newt switches the cellular
      mechanism for limb regeneration from a stem/progenitor-based mechanism (larval
      mode) to a dedifferentiation-based one (adult mode) as it transits beyond
      metamorphosis. We demonstrate that larval newts use stem/progenitor cells such as
      satellite cells for new muscle in a regenerated limb, whereas metamorphosed newts
      recruit muscle fibre cells in the stump for the same purpose. We conclude that
      the newt has evolved novel strategies to secure its regenerative ability of the
      limbs after metamorphosis. 

PMID- 27026264
TI  - An unconventional mechanism of hollow nanorod formation: asymmetric Cu diffusion
      in Au-Cu alloy nanorods during galvanic replacement reaction.
AB  - This study investigates how AuCu3 alloy nanorods transform into hollow rods
      during a galvanic replacement reaction. An unusual reaction intermediate was
      observed where the solid nanorod became partially hollow and Cu rich at one end.
      This was attributed to simultaneous galvanic replacement and asymmetric diffusion
      of Cu due to the Kirkendall effect. The hollow Au-Cu nanorods showed enhanced
      catalytic activity for p-nitrophenol reduction. 

PMID- 27026265
TI  - Dynamic analysis of a fractional order delayed predator-prey system with
      harvesting.
AB  - In the study, we consider a fractional order delayed predator-prey system with
      harvesting terms. Our discussion is divided into two cases. Without harvesting,
      we investigate the stability of the model, as well as deriving some criteria by
      analyzing the associated characteristic equation. With harvesting, we investigate
      the dynamics of the system from the aspect of local stability and analyze the
      influence of harvesting to prey and predator. Finally, numerical simulations are
      presented to verify our theoretical results. In addition, using numerical
      simulations, we investigate the effects of fractional order and harvesting terms
      on dynamic behavior. Our numerical results show that fractional order can affect
      not only the stability of the system without harvesting terms, but also the
      switching times from stability to instability and to stability. The harvesting
      can convert the equilibrium point, the stability and the stability switching
      times. 

PMID- 27026266
TI  - Morvan's syndrome and myasthenia gravis related to familial Mediterranean fever
      gene mutations.
AB  - BACKGROUND: We present the first case of Morvan's syndrome (MoS) and myasthenia
      gravis (MG) related to familial Mediterranean fever (FMF) gene mutations. CASE
      PRESENTATION: A 40-year-old woman with a 1-year history of bilateral ptosis and
      limb muscle weakness presented to our hospital. She also had memory impairment,
      insomnia, hyperhidrosis, and muscle twitches. Electromyography confirmed
      widespread myokymia, and there was evidence of temporal region dysfunction on
      electroencephalography. Anti-voltage-gated potassium channel complex antibodies
      and anti-acetylcholine receptor antibodies were both positive. Edrophonium
      administration was effective for bilateral ptosis and muscle weakness. She and
      her family experienced self-limiting febrile attacks with arthralgia, which led
      us to suspect FMF. Genetic analyses revealed compound heterozygous mutations in
      exon 2 of the MEFV gene (L110P/E148Q). From these findings, a diagnosis of MoS
      and MG complicated with MEFV gene mutations was made. Intravenous high-dose
      corticosteroids, plasma exchange, and intravenous immunoglobulin resulted in only
      transient, limited improvement, and frequent relapses, especially in the
      myasthenic symptoms. Interleukin (IL)-6, IL-1beta, and tumor necrosis factor
      alpha were markedly elevated in the serum, which was considered to be derived
      from the MEFV mutations and responsible for the resistance to immunotherapy.
      CONCLUSION: The present case illustrates a possible link between auto
      inflammation and auto-antibody-mediated neurological diseases.

PMID- 27026267
TI  - Usability Testing of an Internet-Based e-Counseling Platform for Adults With
      Chronic Heart Failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is a major cause of hospitalization and
      mortality. In order to maintain heart function and quality of life, patients with
      CHF need to follow recommended self-care guidelines (ie, eating a heart healthy
      diet, exercising regularly, taking medications as prescribed, monitoring their
      symptoms, and living a smoke-free life). Yet, adherence to self-care is poor. We
      have developed an Internet-based e-Counseling platform, Canadian e-Platform to
      Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT), that
      aims to improve self-care adherence and quality of life in people with CHF.
      Before assessing the efficacy of this e-platform in a multisite, double-blind,
      randomized controlled trial, we evaluated the usability of the prototype website.
      OBJECTIVE: The objective of the study was to assess the usability of the CHF
      CePPORT e-Counseling platform in terms of navigation, content, and layout.
      METHODS: CHF patients were purposively sampled from the Heart Function Clinic at
      the Peter Munk Cardiac Center, University Health Network, to participate in this
      study. We asked the consented participants to perform specific tasks on the
      website. These tasks included watching self-help videos and reviewing content as
      directed. Their interactions with the website were captured using the "think
      aloud" protocol. After completing the tasks, research personnel conducted a semi
      structured interview with each participant to assess their experience with the
      website. Content analysis of the transcripts from the "think aloud" sessions and
      the interviews was conducted to identify themes related to navigation, content,
      and layout of the website. Descriptive statistics were used to summarize the
      satisfaction data. RESULTS: A total of 7 men and women (ages 39-77) participated
      in 2 iterative rounds of testing. Overall, all participants were very satisfied
      with the content and layout of the website. They reported that the content was
      helpful to their management of CHF and that it reflected their experiences in
      coping with CHF. The layout was professional and friendly. The use of videos made
      the learning process entertaining. However, they experienced many navigation
      errors in the first round of testing. For example, some participants were not
      sure how to navigate across a series of Web pages. Based on the experiences that
      were reported in the first round, we made several changes to the navigation
      structure. This included using large navigation buttons to direct users to each
      section and providing tutorial videos to familiarize users with our website. We
      assessed whether these changes improved user navigation in the second round of
      testing. The major finding is that participants made fewer navigation errors and
      they did not identify any new problems. CONCLUSIONS: We found evidence to support
      the usability of our CHF-CePPORT e-Counseling platform. Our findings highlight
      the importance of a clear and easy-to-follow navigation structure on user
      experience.

PMID- 27026268
TI  - Androgen receptor and metastasis-associated protein-1 are frequently expressed in
      estrogen receptor negative/HER2 positive breast cancer.
AB  - The prognostic value of androgen receptor (AR) and its related molecules in
      breast cancer is not well characterized. We retrospectively investigated 120
      ER(+) and 120 ER(-) invasive breast cancers of 240 women, who were treated at our
      institution between January 2008 and December 2009. We excluded in situ,
      recurrent, metastatic, and bilateral carcinomas as well as non-epithelial
      lesions. Median follow-up was 74 months. Immunohistochemical assessment of
      expression of AR and metastasis-associated protein-1 (MTA1) resulted in 59.2 % (n
      = 142) AR(+) and 36.7 % (n = 88) high MTA1 expressing (MTA1(High)) carcinomas.
      MTA1(High) tumors were significantly more often ER(-), while AR(+) tumors were
      significantly more often HER2(+) (p < 0.01). MTA1(High)/ER(-) tumors were more
      often AR(-)/HER2(-) (p < 0.01). Patients with an AR(+)/ER(+) tumor had better
      disease-free survival (DFS; p = 0.011). Patients with an ER(-)/MTA1(High) tumor
      had significantly shorter DFS (p = 0.006) as well as patients with an
      AR(+)/HER2(+) tumor (p < 0.01). In Cox models, AR expression (HR, 0.248; 95 % CI,
      0.086-0.716) and lymph node status (HR, 6.401; 95 % CI, 1.428-28.686) were
      independent predictors for DFS in ER(+) cancers, whereas AR(+)/HER2(+) expression
      status (HR, 2.927; 95 % CI, 1.256-6.821) and lymph node status (HR, 2.690; 95 %
      CI, 1.041-7.840) were independent predictors for DFS in ER(-) cancers. We show
      that AR might be an additional marker for endocrine responsiveness in ER(+)
      cancers and suggests that blocking MTA1 might be an effective way to inhibit
      AR/HER2 signaling in ER(-) breast cancer. 

PMID- 27026270
TI  - Does flat epithelial atypia have rounder nuclei than columnar cell
      change/hyperplasia? A morphometric approach to columnar cell lesions of the
      breast.
AB  - Columnar cell lesions of the breast encompass columnar cell change/hyperplasia
      (CCC/CCH) and flat epithelial atypia (FEA). These have attracted researchers
      because emerging data suggest that FEA may represent the earliest histologically
      detectable non-obligate precursor of breast cancer. However, it is occasionally
      difficult to distinguish FEA from CCC/CCH because of similar histology. Although
      the nuclei of FEA are frequently described as relatively round compared with
      those of CCC/CCH, there are few morphometric studies to support this statement.
      The aim of this study was to provide objective data as to the nuclear shape in
      columnar cell lesions. As a shape descriptor, we adopted ellipticity that is
      defined by the formula 2b/2a, where a is the length of the long axis of the
      ellipse and b is the length of the short axis. Contrary to circularity,
      ellipticity reflects the overall configuration of an ellipse irrespective of
      surface irregularity. Our image analysis included generating whole slide images,
      extracting glandular cell nuclei, measuring nuclear ellipticity, and
      superimposing graded colors based on execution of results on the captured images.
      A total of 7917 nuclei extracted from 22 FEA images and 5010 nuclei extracted
      from 13 CCC/CCH images were analyzed. There was a significant difference in
      nuclear roundness between FEA and CCC/CCH with mean ellipticity values of 0.723
      and 0.679, respectively (p < 0.001, Welch's t test). Furthermore, FEA with
      malignancy had significantly rounder nuclei than FEA without malignancy (p <
      0.001). Our preliminary results suggest that nuclear ellipticity is a key
      parameter in reproducibly classifying columnar cell lesions of the breast. 

PMID- 27026269
TI  - Expression of cell cycle markers is predictive of the response to primary
      systemic therapy of locally advanced breast cancer.
AB  - We aimed to analyze to what extent expression of four cell cycle regulation
      markers-minichromosome maintenance protein (MCM2), Ki-67, cyclin A, and
      phosphohistone-H3 (PHH3)-predict response to primary systemic therapy in terms of
      pathological complete remission (pCR). In search of an accurate and reproducible
      scoring method, we compared computer-assisted (CA) and routine visual assessment
      (VA) of immunoreactivity. We included 57 patients with breast cancer in the
      study. The cell cycle markers were detected using immunohistochemistry on pre
      therapy core biopsy samples. Parallel CA (validated by manual labeling) and
      standard VA were performed and compared for diagnostic agreement and predictive
      value for pCR. CA and VA results were dichotomized based on receiver operating
      characteristic analysis defined optimal cut-off values. "High" was defined by
      staining scores above the optimal cut-off, while "low" had staining scores below
      the optimal cut-off. The CA method resulted in significantly lower values for Ki
      67 and MCM2 compared to VA (mean difference, -3.939 and -4.323). Diagnostic
      agreement was highest for cyclin A and PHH3 (-0.586 and -0.666, respectively).
      Regardless of the method (CA/VA) used, all tested markers were predictive of pCR.
      Optimal cut-off-based dichotomization improved diagnostic agreement between the
      CA and VA methods for every marker, in particular for MCM2 (kappa = 1, p <
      0.000). Cyclin A displayed excellent agreement (kappa = 0.925; p < 0.000), while
      Ki-67 and PHH3 showed good agreement (kappa = 0.789, p < 0.000 and kappa = 0.794,
      p < 0.000, respectively). We found all cell cycle markers (Ki-67, MCM2, cyclin A,
      and PHH3) predictive of pCR. Diagnostic agreement between CA and VA was better at
      lower staining scores but improved after optimal cut-off-based dichotomization. 

PMID- 27026271
TI  - Early [(18)F]florbetaben and [(11)C]PiB PET images are a surrogate biomarker of
      neuronal injury in Alzheimer's disease.
AB  - PURPOSE: [(18)F]FDG is a commonly used neuronal injury biomarker for early and
      differential diagnosis of dementia. Typically, the blood supply to the brain is
      closely coupled to glucose consumption. Early uptake of the Abeta tracer
      [(11)C]PiB on PET images is mainly determined by cerebral blood flow and shows a
      high correlation with [(18)F]FDG uptake. Uptake data for (18)F-labelled Abeta PET
      tracers are, however, scarce. We investigated the value of early PET images using
      the novel Abeta tracer [(18)F]FBB in the diagnosis of Alzhimers disease (AD).
      METHODS: This retrospective analysis included 22 patients with MCI or dementia
      who underwent dual time-point PET imaging with either [(11)C]PiB (11 patients) or
      [(18)F]FBB (11 patients) in routine clinical practice. Images were acquired 1 - 9
      min after administration of both tracers and 40 - 70 min and 90 - 110 min after
      administration of [(11)C]PiB and [(18)F]FBB, respectively. The patients also
      underwent [(18)F]FDG brain PET imaging. PET data were analysed visually and
      semiquantitatively. Associations between early Abeta tracer uptake and dementia
      as well as brain atrophy were investigated. RESULTS: Regional visual scores of
      early Abeta tracer and [(18)F]FDG PET images were significantly correlated
      (Spearman's rho = 0.780, P < 0.001). Global brain visual analysis revealed
      identical results between early Abeta tracer and [(18)F]FDG PET images. In a VOI
      based analysis, the early Abeta tracer data correlated significantly with the
      [(18)F]FDG data (r = 0.779, P < 0.001), but there were no differences between
      [(18)F]FBB and [(11)C]PiB. Cortical SUVRs in regions typically affected in AD on
      early Abeta tracer and [(18)F]FDG PET images were correlated with MMSE scores
      (rho = 0.458, P = 0.032, and rho = 0.456, P = 0.033, respectively). A voxel-wise
      group-based search for areas with relatively higher tracer uptake on early Abeta
      tracer PET images compared with [(18)F]FDG PET images revealed a small cluster in
      the midbrain/pons; no significant clusters were found for the opposite
      comparison. CONCLUSION: Early [(18)F]FBB and [(11)C]PiB PET brain images are
      similar to [(18)F]FDG PET images in AD patients, and these tracers could
      potentially be used as biomarkers in place of [(18)F]FDG. Thus, Abeta tracer PET
      imaging has the potential to provide biomarker information on AD pathology and
      neuronal injury. The potential of this approach for supporting the diagnosis of
      AD needs to be confirmed in prospective studies in larger cohorts.

PMID- 27026272
TI  - Is outpatient robotic pyeloplasty feasible?
AB  - With increased experience, many laparoscopic procedures have evolved from
      mandatory same-day admission to the outpatient setting. Given the shorter
      operative time and length of stay, the potential to perform robotic surgery as an
      outpatient procedure exists. We sought to describe our initial experience with
      performing robotic-assisted laparoscopic pyeloplasty (RP) on children in an
      outpatient setting. We retrospectively reviewed a prospectively collected
      database of all patients undergoing RP from July 2012 to May 2014 by a single
      surgeon. All patients discharged home within 12 h of completion of surgery were
      included in the analysis. Prior to discharge the Wong-Baker Pain Scale 1-10 was
      reviewed and given to all patients. All patients were prescribed oxybutynin and
      phenazopyridine for bladder spasms and stent discomfort. Post-operative follow-up
      telephone calls were made inquiring about oral intake, pain control,
      constitutional symptoms, and voiding issues. Readmission rates and post-operative
      outcomes were reviewed. During the study period, 62 children underwent RP and 13
      patients (21 %) were selected for outpatient management. These 7 boys and 6 girls
      had a mean age of 8.1 years old. Of the 13 patients, 11 patients had left-sided
      procedures and 2 had right; all had primary UPJO. Mean pain score was 2.7 in the
      first 12 h at home. Within 24 h, the pain score decreased to a mean of 2.2. No
      patient required opioid analgesics and no child required admission after surgery.
      At 3-month follow-up, 7 patients had resolved hydronephrosis, 5 had improved
      hydronephrosis and 1 was unchanged. MAG3 renal scan in the latter patient showed
      no sign of obstruction. Outpatient RP is feasible and appears to be safe. Great
      care must be taken when selecting which patients can be fast tracked. 

PMID- 27026273
TI  - Cultural Influence on Coping Strategies of Filipino Immigrant Nurses.
AB  - Much of the research on internationally educated nurses (IENs) has focused on the
      challenges they encounter in the United States and how they can best be
      integrated into the workplace. Despite their many challenges, Filipino IENs
      continue to come to the United States and thrive, bringing with them diverse
      experience and knowledge that contribute to the provision of quality care to a
      patient population that is becoming increasingly diverse. Although a substantial
      body of research has been published on IEN coping, fewer studies have focused on
      the influence of culture on Filipino IEN's preferred coping strategies. This
      study contributes to the burgeoning interest in understanding culture's influence
      on coping patterns and preferences among diverse populations. Occupational health
      nurses and administrators can use these findings to develop culturally
      appropriate health promotion programs and interventions to retain quality nurses
      and promote healthier workplaces. 

PMID- 27026274
TI  - Obesity, Prediabetes, and Perceived Stress in Municipal Workers.
AB  - The primary cause of death for men and women in the United States is heart
      disease. Obesity and diabetes are major contributors to heart disease, and the
      risk is worsened in the presence of stress. It is clinically useful to identify
      predictors of obesity and prediabetes in a working population. The purpose of
      this current cross-sectional, correlational study was to examine relationships
      among obesity, prediabetes, and perceived stress in municipal workers using a
      subset of worksite wellness program data from employees screened in 2010 and
      2011. Multiple regression models indicated that age, gender, race, HA1c, shift
      schedule, physical activity, and occupation were significant predictors of
      obesity in municipal workers ( p < .01). Prediabetes in municipal workers was
      predicted by age, Black race, and body mass index (BMI; p < .01). Perceived
      stress was not a significant predictor of obesity or prediabetes in municipal
      workers. Overall, the findings of this study provide guidance to occupational
      health nurses when evaluating individuals in an occupational health setting.
      Further research is needed to examine relationships among the variables and
      validate the models.

PMID- 27026275
TI  - Home-Based Direct Care Workers: Their Reported Injuries and Perceived Training
      Knowledge.
AB  - The objectives of the study were to profile occupational injury patterns across
      home health and hospice care (HHC), organization characteristics, and home health
      aides' (HHAs) individual characteristics, and examine how worker training affects
      HHAs' risk of reporting an injury using the model of human factors of health care
      in the home. The authors measured training knowledge using an 11-item scale and
      conducted univariate and bivariate analyses to describe injury patterns across
      individual, occupational, and organizational factors using STATA 12.0. The
      researchers found that work-related injuries and type of injury were associated
      with increased likelihood of reporting one or more injuries, full-time
      employment, high hourly pay, and working in an inpatient or mixed setting.
      Overall, HHAs perceived that they received "excellent" and "good" training on key
      topics that promoted safety and job knowledge. Furthermore, the results suggested
      linkages between worker's complex personal, occupational, and organizational
      characteristics. 

PMID- 27026276
TI  - Factors Influencing the Decision to Receive an Influenza Vaccination Among
      Manufacturing Plant and Day Care Center Employees.
AB  - To improve influenza immunization rates, it is essential to understand why adults
      are not immunized and the factors that influence their decisions. This
      information can be used to tailor educational materials and outreach. 

PMID- 27026277
TI  - A Fall in the Workplace Leads to a Diagnosis of Parkinson's Disease.
AB  - A 62 year old male worker sustained a head contusion from a fall in the
      workplace. When assessing the mechanism of the fall, it was noted that the worker
      stated that his feet became "stuck" and would not move. He also stated that he
      could not move fast enough to break his fall. Upon physical examination, a
      resting tremor was noted as well as upper and lower body rigidity, and a
      festinating gait. The worker was evaluated by a neurologist and diagnosed with
      early Parkinson's disease. 

PMID- 27026279
TI  - Variable climatic conditions dominate recent phytoplankton dynamics in Chesapeake
      Bay.
AB  - Variable climatic conditions strongly influence phytoplankton dynamics in
      estuaries globally. Our study area is Chesapeake Bay, a highly productive
      ecosystem providing natural resources, transportation, and recreation for nearly
      16 million people inhabiting a 165,000-km(2) watershed. Since World War II,
      nutrient over-enrichment has led to multiple ecosystem impairments caused by
      increased phytoplankton biomass as chlorophyll-a (chl-a). Doubled nitrogen (N)
      loadings from 1945-1980 led to increased chl-a, reduced water clarity, and low
      dissolved oxygen (DO), while decreased N loadings from 1981-2012 suggest modest
      improvement. The recent 30+ years are characterized by high inter-annual
      variability of chl-a, coinciding with irregular dry and wet periods, complicating
      the detection of long-term trends. Here, we synthesize time-series data for
      historical and recent N loadings (TN, NO2 + NO3), chl-a, floral composition, and
      net primary productivity (NPP) to distinguish secular changes caused by nutrient
      over-enrichment from spatio-temporal variability imposed by climatic conditions.
      Wet years showed higher chl-a, higher diatom abundance, and increased NPP, while
      dry years showed lower chl-a, lower diatom abundance, and decreased NPP. Our
      findings support a conceptual model wherein variable climatic conditions dominate
      recent phytoplankton dynamics against a backdrop of nutrient over-enrichment,
      emphasizing the need to separate these effects to gauge progress toward improving
      water quality in estuaries.

PMID- 27026278
TI  - Health economic evaluation of Gd-EOB-DTPA MRI vs ECCM-MRI and multi-detector
      computed tomography in patients with suspected hepatocellular carcinoma in
      Thailand and South Korea.
AB  - OBJECTIVE: The effectiveness of treatment decisions and economic outcomes of
      using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced
      magnetic resonance imaging (Gd-EOB-DTPA-MRI) were compared with extracellular
      contrast media-enhanced MRI (ECCM-MRI) and multi-detector computed tomography
      (MDCT) as initial procedures in patients with suspected hepatocellular carcinoma
      (HCC) in South Korea and Thailand. METHODS: A decision-tree model simulated the
      clinical pathway for patients with suspected HCC from the first imaging procedure
      to a confirmed treatment decision. Input data (probabilities and resource
      consumptions) were estimated and validated by clinical experts. Costs for
      diagnostic alternatives and related treatment options were derived from published
      sources, taking into account both payer's and hospital's perspectives. RESULTS:
      All experts from Korea and Thailand agreed that Gd-EOB-DTPA-MRI yields the
      highest diagnostic certainty and minimizes the need for additional confirmatory
      diagnostic procedures in HCC. In Korea, from the payer's perspective, total cost
      was USD $3087/patient to reach a confirmed treatment decision using Gd-EOB-DTPA
      MRI (vs $3205/patient for MDCT and $3403/patient for ECCM-MRI). From the
      hospital's perspective, Gd-EOB-DTPA-MRI incurred the lowest cost ($2289/patient
      vs $2320/patient and $2528/patient, respectively). In Thailand, Gd-EOB-DTPA-MRI
      was the least costly alternative for the payer ($702/patient vs $931/patient for
      MDCT and $873/patient for ECCM-MRI). From the hospital's perspective, costs were
      $1106/patient, $1178/patient, and $1087/patient for Gd-EOB-DTPA-MRI, MDCT, and
      ECCM-MRI, respectively. CONCLUSIONS: Gd-EOB-DTPA-MRI as an initial imaging
      procedure in patients with suspected HCC provides better diagnostic certainty and
      relevant statutory health insurance cost savings in Thailand and Korea, compared
      with ECCM-MRI and MDCT.

PMID- 27026280
TI  - Multiplexed Affinity-Based Separation of Proteins and Cells Using Inertial
      Microfluidics.
AB  - Isolation of low abundance proteins or rare cells from complex mixtures, such as
      blood, is required for many diagnostic, therapeutic and research applications.
      Current affinity-based protein or cell separation methods use binary 'bind-elute'
      separations and are inefficient when applied to the isolation of multiple low
      abundance proteins or cell types. We present a method for rapid and multiplexed,
      yet inexpensive, affinity-based isolation of both proteins and cells, using a
      size-coded mixture of multiple affinity-capture microbeads and an inertial
      microfluidic particle sorter device. In a single binding step, different targets
      cells or proteins-bind to beads of different sizes, which are then sorted by
      flowing them through a spiral microfluidic channel. This technique performs
      continuous-flow, high throughput affinity-separation of milligram-scale protein
      samples or millions of cells in minutes after binding. We demonstrate the
      simultaneous isolation of multiple antibodies from serum and multiple cell types
      from peripheral blood mononuclear cells or whole blood. We use the technique to
      isolate low abundance antibodies specific to different HIV antigens and rare HIV
      specific cells from blood obtained from HIV+ patients. 

PMID- 27026281
TI  - Preparation and Loading Process of Single Crystalline Samples into a Gas
      Environmental Cell Holder for In Situ Atomic Resolution Scanning Transmission
      Electron Microscopic Observation.
AB  - A reproducible way to transfer a single crystalline sample into a gas
      environmental cell holder for in situ transmission electron microscopic (TEM)
      analysis is shown in this study. As in situ holders have only single-tilt
      capability, it is necessary to prepare the sample precisely along a specific zone
      axis. This can be achieved by a very accurate focused ion beam lift-out
      preparation. We show a step-by-step procedure to prepare the sample and transfer
      it into the gas environmental cell. The sample material is a GaP/Ga(NAsP)/GaP
      multi-quantum well structure on Si. Scanning TEM observations prove that it is
      possible to achieve atomic resolution at very high temperatures in a nitrogen
      environment of 100,000 Pa.

PMID- 27026282
TI  - Arginine methyltransferases in normal and malignant hematopoiesis.
AB  - Arginine methylation is an abundant covalent modification that regulates diverse
      cellular processes, including transcription, translation, DNA repair, and RNA
      processing. The enzymes that catalyze these marks are known as the protein
      arginine methyltransferases (PRMTs), and they can generate asymmetric dimethyl
      arginine (type I arginine methyltransferases), symmetric dimethylarginine (type
      II arginine methyltransferases), or monomethyarginine (type III arginine
      methyltransferases). The PRMTs are capable of modifying diverse substrates, from
      histone components to specific nuclear and cytoplasmic proteins. Additionally,
      the PRMTs can orchestrate chromatin remodeling by blocking the docking of other
      epigenetic modifying enzymes or by recruiting them to specific gene loci. In the
      hematopoietic system, PRMTs can regulate cell behavior, including the critical
      balance between stem cell self-renewal and differentiation, in at least two
      critical ways, via (i) the covalent modification of transcription factors and
      (ii) the regulation of histone modifications at promoters critical to cell fate
      determination. Given these important functions, it is not surprising that these
      processes are altered in hematopoietic malignancies, such as acute myeloid
      leukemia, where they promote increased self-renewal and impair hematopoietic stem
      and progenitor cell differentiation.

PMID- 27026283
TI  - Cytokine polymorphisms in sickle cell disease and the relationship with cytokine
      expression.
AB  - Sickle cell disease is a chronic inflammatory condition characterized by elevated
      levels of inflammatory cytokines, which may be regulated by genetic polymorphisms
      and could be associated with diverse disease presentations and alloimmunization.
      The aim of this study was to evaluate Treg and Th17 cell frequencies, cytokine
      gene polymorphisms, and their association with cytokine expression profile in
      patients with sickle cell disease. For that purpose, we evaluated the IL intron 3
      variable number tandem repeat (VNTR, genotypes 1.1, 1.2, 2.2, and 2.3), IL4
      T590C>T, IL6-174G>C, TNFalpha-308G>A, IL10-819T>C, IL10-592A>C, and IL10-1082A>G
      polymorphisms and their correlation with TGFbeta, IL4, IL6, and IL10 gene
      expression in sickle cell patients. We observed a significant decrease in Treg
      frequency together with a substantial increase in Th17 response in patients with
      sickle cell disease compared with healthy controls (p < 0.001 and p = 0.014,
      respectively). There was also a higher prevalence of the IL4-590T/T genotype in
      patients with sickle cell disease than in Afro-Brazilian descendent controls (p <
      0.001) and higher expression of IL4 in patients with the 1.1 genotype of IL4
      intron 3 VNTR (p = 0.06). Significantly greater gene expression of TGFbeta, IL6,
      and IL10 was observed in sickle cell patients when compared with controls (p =
      0.01, 0.03, and <0.001, respectively). Moreover, higher levels of interleukin-6
      and -10 were observed in the group of alloimmunized patients. These new data
      bring insights into the deregulation in the immune system affecting sickle cell
      patients and must be further investigated in larger cohorts to better
      characterize individual variations in immune responses and new markers for
      disease morbidity.

PMID- 27026284
TI  - Second-Generation Cryoballoon Ablation in the Setting of Lone Paroxysmal Atrial
      Fibrillation: Single Procedural Outcome at 12 Months.
AB  - BACKGROUND: Lone atrial fibrillation (LAF) develops in younger individuals
      without cardiovascular or pulmonary disease. As pulmonary vein isolation has been
      recognized as an optimal treatment for drug-resistant atrial fibrillation,
      cryoballoon ablation with second-generation balloon (CB-A) may be an ideal
      solution for LAF patients. OBJECTIVE: The aim of this study was to investigate
      acute success, periprocedural complications and outcome over a 12-month follow-up
      period in a cohort of patients having undergone PV isolation (PVI) for LAF using
      CB-A technology. METHODS: A total of 75 consecutive patients (50 male, mean age
      47 +/- 12 years) with a diagnosis of lone paroxysmal atrial fibrillation who
      underwent pulmonary vein isolation (PVI) by CB-A from June 2012 were included.
      All patients underwent this procedure with the 28 mm CB-A. A total of 299 PVs
      (100%) could be isolated with CB-A alone. RESULTS: The freedom from AF recurrence
      after a single procedure was 92% of patients during the entire 13-month follow
      up. When considering a blanking period (BP) of 3 months, success rate was 93.3%.
      Transient phrenic nerve palsy (PNP) was the most frequent complication, occurring
      in 5.3% of individuals (4 patients); complete recovery was documented for all of
      these patients prior to hospital discharge. CONCLUSIONS: CB-A is extremely
      effective in achieving PVI and affords freedom from AF at 13-month follow-up in
      93% of young patients affected by drug-resistant LPAF following a 3-month BP. The
      most frequent complication observed was PNP, which reverted prior to discharge in
      all patients.

PMID- 27026285
TI  - Usefulness of the early molecular diagnosis of Q fever and rickettsial diseases
      in patients with fever of intermediate duration.
AB  - Most cases of fever of intermediate duration (FDI) in Spain are associated with
      infectious diseases (mainly Q fever and rickettsia infections). In clinical
      practice, the causal diagnosis of these entities is based on immunodiagnostic
      techniques, which are of little help in the early stages. Therefore, the aim of
      this study was to evaluate the usefulness of molecular techniques for the early
      diagnosis of Q fever and rickettsia diseases in patients with FDI. A PCR method
      was used to detect the presence of genetic material of Coxiella burnetii and
      Rickettsia spp. in blood specimens from 271 patients with FDI. The specificity of
      both techniques is high, allowing diagnosis in cases undiagnosed by specific
      antibodies detection. These data suggest that the use of molecular techniques,
      with proper selection of the study specimen, and using appropriate primers is a
      useful tool in the early diagnosis of the main causes of FDI, especially if
      serology is negative or inconclusive.

PMID- 27026286
TI  - Pararhizobium polonicum sp. nov. isolated from tumors on stone fruit rootstocks.
AB  - Five Gram-negative, rod-shaped, non-spore-forming bacteria were isolated from
      galls on different stone fruit rootstocks in Poland: strains F5.1(T) and F5.3
      from Prunus avium F12/1, strains CP3.5 and CP17.2.1 from Prunus avium and strain
      AL5.1.8 from Prunus cerasifera. On the basis of 16S rDNA phylogeny, the strains
      cluster together and belong to the genus Pararhizobium with type strain of
      Pararhizobium herbae (99.6-99.8%) as their closest relative. Phylogenetic
      analysis of the novel strains using housekeeping genes atpD, recA and rpoB
      revealed their distinct position separate from other known Rhizobium species and
      confirmed their relation to P. herbae. DNA-DNA hybridization of strains F5.1(T),
      with the type strain of P. herbae LMG 25718(T) and Pararhizobium giardinii R
      4385(T) revealed 28.3% and 27.9% of DNA-DNA relatedness, respectively. Phenotypic
      and physiological properties differentiate the novel isolates from other closely
      related species. On the basis of the results obtained, the five isolates are
      considered to represent a novel species of the genus Pararhizobium, for which the
      name Pararhizobium polonicum sp. nov. (type strain F5.1(T)=LMG 28610(T)=CFBP
      8359(T)) is proposed. 

PMID- 27026288
TI  - Biological Variation of Plasma and Urinary Markers of Acute Kidney Injury in
      Patients with Chronic Kidney Disease.
AB  - BACKGROUND: Identification of acute kidney injury (AKI) is predominantly based on
      changes in plasma creatinine concentration, an insensitive marker. Alternative
      biomarkers have been proposed. The reference change value (RCV), the point at
      which biomarker change can be inferred to have occurred with statistical
      certainty, provides an objective assessment of change in serial tests results in
      an individual. METHODS: In 80 patients with chronic kidney disease, weekly
      measurements of blood and urinary biomarker concentrations were undertaken over 6
      weeks. Variability was determined and compared before and after adjustment for
      urinary creatinine and across subgroups stratified by level of kidney function,
      proteinuria, and presence or absence of diabetes. RESULTS: RCVs were determined
      for whole blood, plasma, and urinary neutrophil gelatinase-associated lipocalin
      (111%, 59%, and 693%, respectively), plasma cystatin C (14%), creatinine (17%),
      and urinary kidney injury molecule 1 (497%), tissue inhibitor of
      metalloproteinases 2 (454%), N-acetyl-beta-d-glucosaminidase (361%), interleukin
      18 (819%), albumin (430%), and alpha1-microglobulin (216%). Blood biomarkers
      exhibited lower variability than urinary biomarkers. Generally, adjusting urinary
      biomarker concentrations for creatinine reduced (P < 0.05) within-subject
      biological variability (CVI). For some markers, variation differed (P < 0.05)
      between subgroups. CONCLUSIONS: These data can form a basis for application of
      these tests in clinical practice and research studies and are applicable across
      different levels of kidney function and proteinuria and in the presence or
      absence of diabetes. Most of the studied biomarkers have relatively high CVI
      (noise) but also have reported large concentration changes in response to renal
      insult (signal); thus progressive change should be detectable (high signal-to
      noise ratio) when baseline data are available.

PMID- 27026287
TI  - Visualizing spatial distribution of alectinib in murine brain using quantitative
      mass spectrometry imaging.
AB  - In the development of anticancer drugs, drug concentration measurements in the
      target tissue have been thought to be crucial for predicting drug efficacy and
      safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly
      used for determination of average drug concentrations; however, complete loss of
      spatial information in the target tissue occurs. Mass spectrometry imaging (MSI)
      has been recently applied as an innovative tool for detection of molecular
      distribution of pharmacological agents in heterogeneous targets. This study
      examined the intra-brain transitivity of alectinib, a novel anaplastic lymphoma
      kinase inhibitor, using a combination of matrix-assisted laser desorption
      ionization-MSI and LC-MS/MS techniques. We first analyzed the pharmacokinetic
      profiles in FVB mice and then examined the effect of the multidrug resistance
      protein-1 (MDR1) using Mdr1a/b knockout mice including quantitative distribution
      of alectinib in the brain. While no differences were observed between the mice
      for the plasma alectinib concentrations, diffuse alectinib distributions were
      found in the brain of the Mdr1a/b knockout versus FVB mice. These results
      indicate the potential for using quantitative MSI for clarifying drug
      distribution in the brain on a microscopic level, in addition to suggesting a
      possible use in designing studies for anticancer drug development and
      translational research. 

PMID- 27026289
TI  - Can 4-port laparoscopic cholecystectomy remain the gold standard for gallbladder
      surgery?
AB  - Since the first laparoscopic cholecystectomy (LC), laparoscopic approach has been
      the focus of surgical authorities and continued its technical revolution. With
      increasing surgical experience, a trend toward even more minimally invasive
      approaches has led to laparoscopic surgery to new inovations. Current surgical
      procedures are: four ports (4PLC), still the gold standart technique, three ports
      (3PLC), two ports (2PLC) and single port laparoscopic cholecystectomy (SPLC).
      Robotic cholecystectomy (RC) and natural orifice translumenal endoscopic surgery
      (NOTES) are the other new techniques for performing cholecystectomy. This article
      aims to make an objective comparision between different types of laparoscopic
      cholecystectomies by using available medical literature. KEY WORDS:
      Cholecystectomy, Laparoscopic, Technique.

PMID- 27026290
TI  - Geometry- and Length Scale-Dependent Deformation and Recovery on Micro- and
      Nanopatterned Shape Memory Polymer Surfaces.
AB  - Micro- and nanoscale surface textures, when optimally designed, present a unique
      approach to improve surface functionalities. Coupling surface texture with shape
      memory polymers may generate reversibly tuneable surface properties. A shape
      memory polyetherurethane is used to prepare various surface textures including 2
      MUm- and 200 nm-gratings, 250 nm-pillars and 200 nm-holes. The mechanical
      deformation via stretching and recovery of the surface texture are investigated
      as a function of length scales and shapes. Results show the 200 nm-grating
      exhibiting more deformation than 2 MUm-grating. Grating imparts anisotropic and
      surface area-to-volume effects, causing different degree of deformation between
      gratings and pillars under the same applied macroscopic strain. Full distribution
      of stress within the film causes the holes to deform more substantially than the
      pillars. In the recovery study, unlike a nearly complete recovery for the
      gratings after 10 transformation cycles, the high contribution of surface energy
      impedes the recovery of holes and pillars. The surface textures are shown to
      perform a switchable wetting function. This study provides insights into how
      geometric features of shape memory surface patterns can be designed to modulate
      the shape programming and recovery, and how the control of reversibly deformable
      surface textures can be applied to transfer microdroplets.

PMID- 27026291
TI  - Sociotechnical Human Factors Involved in Remote Online Usability Testing of Two
      eHealth Interventions.
AB  - BACKGROUND: Research in the fields of human performance technology and human
      computer interaction are challenging the traditional macro focus of usability
      testing arguing for methods that help test moderators assess "use in context"
      (ie, cognitive skills, usability understood over time) and in authentic "real
      world" settings. Human factors in these complex test scenarios may impact on the
      quality of usability results being derived yet there is a lack of research
      detailing moderator experiences in these test environments. Most comparative
      research has focused on the impact of the physical environment on results, and
      rarely on how the sociotechnical elements of the test environment affect
      moderator and test user performance. Improving our understanding of moderator
      roles and experiences with conducting "real world" usability testing can lead to
      improved techniques and strategies OBJECTIVE: To understand moderator experiences
      of using Web-conferencing software to conduct remote usability testing of 2
      eHealth interventions. METHODS: An exploratory case study approach was used to
      study 4 moderators' experiences using Blackboard Collaborate for remote testing
      sessions of 2 different eHealth interventions. Data collection involved audio
      recording iterative cycles of test sessions, collecting summary notes taken by
      moderators, and conducting 2 90-minute focus groups via teleconference. A direct
      content analysis with an inductive coding approach was used to explore personal
      accounts, assess the credibility of data interpretation, and generate consensus
      on the thematic structure of the results. RESULTS: Following the convergence of
      data from the various sources, 3 major themes were identified: (1) moderators
      experienced and adapted to unpredictable changes in cognitive load during
      testing; (2) moderators experienced challenges in creating and sustaining social
      presence and untangling dialogue; and (3) moderators experienced diverse
      technical demands, but were able to collaboratively troubleshoot with test users.
      CONCLUSIONS: Results highlight important human-computer interactions and human
      factor qualities that impact usability testing processes. Moderators need an
      advanced skill and knowledge set to address the social interaction aspects of Web
      based usability testing and technical aspects of conferencing software during
      test sessions. Findings from moderator-focused studies can inform the design of
      remote testing platforms and real-time usability evaluation processes that place
      less cognitive burden on moderators and test users.

PMID- 27026292
TI  - Prevalence of orthostatic hypotension in non-institutionalised elderly aged 80
      and over. A diagnostic study using an oscillometric device.
AB  - BACKGROUND: Orthostatic hypotension (OH) is a common disorder, and possibly
      underdiagnosed. In the elderly, OH has been considered a common cause of falls,
      fractures, and fear of falling. Its prevalence increases with age, probably
      related to the number of drug treatments, decreased fluid intake, and the
      progressive dysfunction of the autonomic nervous system. OBJECTIVES: To evaluate
      the prevalence of OH in a non-institutionalised population >=80 years, according
      to different criteria based on sequential measurements taken at minute 0, 1, 3
      and 5 of standing. METHODS DESIGN: A diagnostic accuracy study using an
      oscillometric device. SETTING AND PARTICIPANTS: Convenience sampling of 176
      people >=80 years attended in an urban Primary Health Care Centre. MEASUREMENTS:
      Supine and standing blood pressure (BP) measurements, at minutes 0, 1, 3 and 5
      using the OMRON 705-CP blood pressure device. OH definition: decrease >=20mmHg in
      systolic BP (SBP) and/or >=10mmHg in diastolic BP (DBP). RESULTS: Mean age
      (Standard Deviation) was 85.2 (3.7) years, and 60.2% were women. Prevalence of
      OH: 30.7% at minute 0; 19.3% at minute 1; 18.2% at minute 3; and 20.5% at minute
      5. Age, sedentary life, smoking, diabetes and SBP values were significantly
      associated with a greater BP decrease at minute 0. CONCLUSION: A third of the
      sample had OH, with a maximum prevalence at minute 0. From a clinical point of
      view, it is suggested that the definition of OH is prioritized according to the
      BP at minute 0.

PMID- 27026293
TI  - Potentiation of cisplatin-induced antiproliferative and apoptotic activities by
      the antiarrhythmic drug procainamide hydrochloride.
AB  - BACKGROUND: We describe the potentiation of antiproliferative and apoptotic
      activities triggered by cis-diamminedichloroplatinum(II) (DDP), and obtained in
      vitro by the co-administration of procainamide hydrochloride (PdHCl) in murine
      P388, and human A2780 and A549 cells. METHODS: We determined the
      antiproliferative and apoptotic activities of DDP and PdHCl combinations by
      different techniques. Moreover, cell cycle analysis, restriction enzyme
      inhibition followed by agarose gel electrophoresis, and TUNEL analysis of tumour
      cells in vivo were also used to strengthen our hypothesis. RESULTS: Our results
      show that PdHCl may significantly increase the inhibition of cell proliferation
      and apoptosis. Experiments in vivo showed that the co-administration of DDP and
      PdHCl increased the percentage of apoptotic cells compared to DDP alone
      treatment, both in subcutaneous (sc) and intraperitoneal (ip) P388 tumours. We
      finally demonstrated that the co-administration of PdHCl prevents DNA digestion
      accounting for a restriction enzyme inhibition that in some cases was greater
      than that obtained by DDP alone. Moreover, when PdHCl was mixed with the reaction
      products (RP) of DDP (RP-PdHCl) we obtained a restriction enzyme inhibition
      greater for some enzymes (Bsp1407I, Hin1II, and Psp1406I) than that obtained by
      the DDP-PdHCl solution. CONCLUSIONS: On the whole our data demonstrate that the
      class I antiarrhythmic drug PdHCl may increase the antiproliferative activity of
      DDP by improving its triggering of apoptosis, and that this phenomenon may be
      likely linked to the formation of a new Pt compound.

PMID- 27026294
TI  - Monitoring mRNA Translation in Neuronal Processes Using Fluorescent Non-Canonical
      Amino Acid Tagging.
AB  - A steady accumulation of experimental data argues that protein synthesis in
      neurons is not merely restricted to the somatic compartment, but also occurs in
      several discrete cellular micro-domains. Local protein synthesis is critical for
      the establishment of synaptic plasticity in mature dendrites and in directing the
      growth cones of immature axons, and has been associated with cognitive impairment
      in mice and humans. Although in recent years a number of important mechanisms
      governing this process have been described, it remains technically challenging to
      precisely monitor local protein synthesis in individual neuronal cell parts
      independent from the soma. This report presents the utility of employing
      microfluidic chambers for the isolation and treatment of single neuronal cellular
      compartments. Furthermore, it is demonstrated that a protein synthesis assay,
      based on fluorescent non-canonical amino acid tagging (FUNCAT), can be combined
      with this cell culture system to label nascent proteins within a discrete
      structural and functional domain of the neuron. Together, these techniques could
      be employed for the detection of protein synthesis within developing and mature
      neurites, offering an effective approach to elucidate novel mechanisms
      controlling synaptic maintenance and plasticity.

PMID- 27026295
TI  - Quantitative Time-Resolved Fluorescence Imaging of Androgen Receptor and Prostate
      Specific Antigen in Prostate Tissue Sections.
AB  - Androgen receptor (AR) and prostate-specific antigen (PSA) are expressed in the
      prostate and are involved in prostate cancer (PCa). The aim of this study was to
      develop reliable protocols for reproducible quantification of AR and PSA in
      benign and malignant prostate tissue using time-resolved fluorescence (TRF)
      imaging techniques. AR and PSA were detected with TRF in tissue microarrays from
      91 PCa patients. p63/ alpha-methylacyl-CoA racemase (AMACR) staining on
      consecutive sections was used to categorize tissue areas as benign or cancerous.
      Automated image analysis was used to quantify staining intensity. AR intensity
      was significantly higher in AMACR+ and lower in AMACR- cancer areas as compared
      with benign epithelium. The PSA intensity was significantly lower in cancer
      areas, particularly in AMACR- glands. The AR/PSA ratio varied significantly in
      the AMACR+ tumor cells as compared with benign glands. There was a trend of more
      rapid disease progression in patients with higher AR/PSA ratios in the AMACR-
      areas. This study demonstrates the feasibility of developing reproducible
      protocols for TRF imaging and automated image analysis to study the expression of
      AR and PSA in benign and malignant prostate. It also highlighted the differences
      in AR and PSA protein expression within AMACR- and AMACR+ cancer regions.

PMID- 27026296
TI  - A Systematic Characterization of Aquaporin-9 Expression in Human Normal and
      Pathological Tissues.
AB  - AQP9 is known to facilitate hepatocyte glycerol uptake. Murine AQP9 protein
      expression has been verified in liver, skin, epididymis, epidermis and neuronal
      cells using knockout mice. Further expression sites have been reported in humans.
      We aimed to verify AQP9 expression in a large set of human normal organs,
      different cancer types, rheumatoid arthritis synovial biopsies as well as in cell
      lines and primary cells. Combining standardized immunohistochemistry with high
      throughput mRNA sequencing, we found that AQP9 expression in normal tissues was
      limited, with high membranous expression only in hepatocytes. In cancer tissues,
      AQP9 expression was mainly found in hepatocellular carcinomas, suggesting no
      general contribution of AQP9 to carcinogenesis. AQP9 expression in a subset of
      rheumatoid arthritis synovial tissue samples was affected by Humira, thereby
      supporting a suggested role of TNFalpha in AQP9 regulation in this disease. Among
      cell lines and primary cells, LP-1 myeloma cells expressed high levels of AQP9,
      whereas low expression was observed in a few other lymphoid cell lines. AQP9 mRNA
      and protein expression was absent in HepG2 hepatocellular carcinoma cells.
      Overall, AQP9 expression in human tissues appears to be more selective than in
      mice.

PMID- 27026297
TI  - Detection of Phenotypic Alterations Using High-Content Analysis of Whole-Slide
      Images.
AB  - Tumors exhibit spatial heterogeneity, as manifested in immunohistochemistry (IHC)
      staining patterns. Current IHC quantification methods lose information by
      reducing this heterogeneity in each whole-slide image (WSI) or in selective
      fields of view to a single staining index. The aim of this study was to
      investigate the sensitivity of an IHC quantification method that uses this
      heterogeneity to reliably compare IHC staining patterns. We virtually partitioned
      WSIs by a grid of square tiles, and computed the staining index distributions to
      quantify heterogeneities. We used samples from these distributions as inputs to
      non-parametric statistical comparisons. We applied our grid method to fixed tumor
      samples from 26 tumors obtained from a double-blind preclinical study of a
      patient-derived orthotopic xenograft model of pediatric neuroblastoma in CD1 nude
      mice. We compared the results of our grid method to the results based on whole
      slide indices, the current practice. We show that our grid method reliably
      detects phenotypic alterations that other tests based on whole-slide indices fail
      to detect. Based on robustness and increased sensitivity of statistical
      inference, we conclude that our method of whole-slide grid quantification is
      superior to existing whole-slide quantification techniques.

PMID- 27026298
TI  - Brain Health: A Chinese Geriatrician's Viewpoint.

PMID- 27026301
TI  - Dosage of copy number variation at 22q11.2 mediates changes in cognition, social
      function and brain structure in autism spectrum disorder.
AB  - Microdeletion at 22q11.2, a common copy number variation (CNV) noted in
      neurodevelopmental disorders, may be associated with cognitive impairment.
      However, cognitive function in individuals with microduplication remains unclear.
      This work presents the genetic, clinical, and brain structural data of two men
      out of 335 probands with autistic spectrum disorder (ASD) who had different CNV
      dosages at 22q11.2, and comparison with their siblings, 55 ASD probands, and 73
      controls. Both showed severe autistic symptoms, but the proband with
      microduplication demonstrated better cognitive functions. Furthermore, different
      cingulate gyrus volume changes were noted, indicating that the proband with
      22q11.2 microduplication had a different pattern of cingulate gyrus structure.
      Our comprehensive characterization of the behavioral, cognitive, and imaging
      phenotypes of ASD probands with different CNV dosage at 22q11.2 contribute to how
      copy number changes at 22q11.2 mediate the phenotypes in ASD, and pave the way
      for future clinical and functional study on these variants. 

PMID- 27026303
TI  - Rethinking the Balance of Risk and Benefit of Androgen Deprivation Therapy for
      Intermediate-Risk Prostate Cancer.

PMID- 27026302
TI  - Post-Exposure Exercise Fails to Ameliorate Memory Impairment Induced by Propofol
      and Ketamine in Developing Rats.
AB  - BACKGROUND: This aim of this study was to determine the effects of ketamine
      propofol combination on learning and memory, as well as exercise, on anesthetic
      neurotoxicity. MATERIAL/METHODS: A ketamine-propofol combination was administered
      once (group SKP, Single Ketamine Propofol) on P7 (postnatal day 7) or in 3
      treatments on P6, P8, and P10 (group MKP, Multiple Ketamine Propofol). Rat pups
      in group C (Control) received equivalent volumes of normal saline in 3 injections
      on P6, P8, and P10. Rats designated MKPR (Multiple Ketamine Propofol and running)
      and CR (Control and running) began running exercise on P21 on wheels. Learning
      and memory was assessed by Morris water maze and fear conditioning tests.
      Hippocampal neurogenesis of rats was detected by BrdU immunofluorescence.
      RESULTS: MKP rats had longer latency to platform than group C during training in
      the Morris water maze; SKP rats stayed in the target quadrant longer than MKP
      rats during testing (P<0.05). Rats in running groups had shorter latency than non
      running rats, but running had no interaction with anesthesia exposure.
      CONCLUSIONS: Repeat ketamine-propofol combination doses increase risk of memory
      impairment in developing rats. Running has no impact on anesthetic neurotoxicity.

PMID- 27026300
TI  - Chromatin remodeling effects on enhancer activity.
AB  - During organism development, a diversity of cell types emerges with disparate,
      yet stable profiles of gene expression with distinctive cellular functions. In
      addition to gene promoters, the genome contains enhancer regulatory sequences,
      which are implicated in cellular specialization by facilitating cell-type and
      tissue-specific gene expression. Enhancers are DNA binding elements characterized
      by highly sophisticated and various mechanisms of action allowing for the
      specific interaction of general and tissue-specific transcription factors (TFs).
      However, eukaryotic organisms package their genetic material into chromatin,
      generating a physical barrier for TFs to interact with their cognate sequences.
      The ability of TFs to bind DNA regulatory elements is also modulated by changes
      in the chromatin structure, including histone modifications, histone variants,
      ATP-dependent chromatin remodeling, and the methylation status of DNA.
      Furthermore, it has recently been revealed that enhancer sequences are also
      transcribed into a set of enhancer RNAs with regulatory potential. These
      interdependent processes act in the context of a complex network of chromatin
      interactions, which together contributes to a renewed vision of how gene
      activation is coordinated in a cell-type-dependent manner. In this review, we
      describe the interplay between genetic and epigenetic aspects associated with
      enhancers and discuss their possible roles on enhancer function.

PMID- 27026304
TI  - Exposure Risks Among Children Undergoing Radiation Therapy: Considerations in the
      Era of Image Guided Radiation Therapy.
AB  - Recent improvements in toxicity profiles of pediatric oncology patients are
      attributable, in part, to advances in the field of radiation oncology such as
      intensity modulated radiation (IMRT) and proton therapy (IMPT). While IMRT and
      IMPT deliver highly conformal dose to targeted volumes, they commonly demand the
      addition of 2- or 3-dimensional imaging for precise positioning--a technique
      known as image guided radiation therapy (IGRT). In this manuscript we address
      strategies to further minimize exposure risk in children by reducing effective
      IGRT dose. Portal X rays and cone beam computed tomography (CBCT) are commonly
      used to verify patient position during IGRT and, because their relative radiation
      exposure is far less than the radiation absorbed from therapeutic treatment
      beams, their sometimes significant contribution to cumulative risk can be easily
      overlooked. Optimizing the conformality of IMRT/IMPT while simultaneously
      ignoring IGRT dose may result in organs at risk being exposed to a greater
      proportion of radiation from IGRT than from therapeutic beams. Over a treatment
      course, cumulative central-axis CBCT effective dose can approach or supersede the
      amount of radiation absorbed from a single treatment fraction, a theoretical
      increase of 3% to 5% in mutagenic risk. In select scenarios, this may result in
      the underprediction of acute and late toxicity risk (such as azoospermia, ovarian
      dysfunction, or increased lifetime mutagenic risk) in radiation-sensitive organs
      and patients. Although dependent on variables such as patient age, gender,
      weight, body habitus, anatomic location, and dose-toxicity thresholds, modifying
      IGRT use and acquisition parameters such as frequency, imaging modality, beam
      energy, current, voltage, rotational degree, collimation, field size,
      reconstruction algorithm, and documentation can reduce exposure, avoid
      unnecessary toxicity, and achieve doses as low as reasonably achievable,
      promoting a culture and practice of "gentle IGRT."

PMID- 27026299
TI  - The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an
      integrative overview.
AB  - Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease
      destroying articular cartilage and bone. The female preponderance and the
      influence of reproductive states in RA have long linked this disease to sexually
      dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune
      enhancing properties and increases in the circulation of some patients with RA.
      However, PRL also suppresses the immune system, stimulates the formation and
      survival of joint tissues, acquires antiangiogenic properties upon its cleavage
      to vasoinhibins, and protects against joint destruction and inflammation in the
      adjuvant-induced model of RA. This review addresses risk factors for RA linked to
      PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and
      immune cells, and the clinical and experimental data associating PRL with RA.
      This information provides important insights into the pathophysiology of RA and
      highlights protective actions of the PRL/vasoinhibin axis that could lead to
      therapeutic benefits.

PMID- 27026305
TI  - Identifying Predictive Factors for Incident Reports in Patients Receiving
      Radiation Therapy.
AB  - PURPOSE: To describe radiation therapy cases during which voluntary incident
      reporting occurred; and identify patient- or treatment-specific factors that
      place patients at higher risk for incidents. METHODS AND MATERIALS: We used our
      institution's incident learning system to build a database of patients with
      incident reports filed between January 2011 and December 2013. Patient- and
      treatment-specific data were reviewed for all patients with reported incidents,
      which were classified by step in the process and root cause. A control group of
      patients without events was generated for comparison. Summary statistics,
      likelihood ratios, and mixed-effect logistic regression models were used for
      group comparisons. RESULTS: The incident and control groups comprised 794 and 499
      patients, respectively. Common root causes included documentation errors (26.5%),
      communication (22.5%), technical treatment planning (37.5%), and technical
      treatment delivery (13.5%). Incidents were more frequently reported in minors
      (age <18 years) than in adult patients (37.7% vs 0.4%, P<.001). Patients with
      head and neck (16% vs 8%, P<.001) and breast (20% vs 15%, P=.03) primaries more
      frequently had incidents, whereas brain (18% vs 24%, P=.008) primaries were less
      frequent. Larger tumors (17% vs 10% had T4 lesions, P=.02), and cases on protocol
      (9% vs 5%, P=.005) or with intensity modulated radiation therapy/image guided
      intensity modulated radiation therapy (52% vs 43%, P=.001) were more likely to
      have incidents. CONCLUSIONS: We found several treatment- and patient-specific
      variables associated with incidents. These factors should be considered by
      treatment teams at the time of peer review to identify patients at higher risk.
      Larger datasets are required to recommend changes in care process standards, to
      minimize safety risks.

PMID- 27026306
TI  - Variations in Medicare Reimbursement in Radiation Oncology: An Analysis of the
      Medicare Provider Utilization and Payment Data Set.
AB  - PURPOSE: The purposes of this study were to summarize recently published data on
      Medicare reimbursement to individual radiation oncologists and to identify the
      causes of variation in Medicare reimbursement in radiation oncology. METHODS AND
      MATERIALS: The Medicare Provider Utilization and Payment Data: Physician and
      Other Supplier Public Use File (POSPUF), which details nearly all services
      provided by radiation oncologists in 2012, was used for this study. The data were
      filtered and analyzed by physician and by billing code. Statistical analysis was
      performed to identify differences in reimbursements based on sex, rurality,
      billing of technical services, or location in a certificate of need (CON) state.
      RESULTS: There were 4135 radiation oncologists who received a total of
      $1,499,625,803 in payments from Medicare in 2012. Seventy-five percent of
      radiation oncologists were male. The median reimbursement was $146,453. The code
      with the highest total reimbursement was 77418 (radiation treatment delivery
      intensity modulated radiation therapy [IMRT]). The most commonly billed
      evaluation and management (E/M) code for new visits was 99205 (49%). The most
      commonly billed E/M code for established visits was 99213 (54%). Forty percent of
      providers billed none of their new office visits using 99205 (the highest E/M
      billing code), whereas 34% of providers billed all of their new office visits
      using 99205. For the 1510 radiation oncologists (37%) who billed technical
      services, median Medicare reimbursement was $606,008, compared with $93,921 for
      all other radiation oncologists (P<.001). On multivariate analysis, technical
      services billing (P<.001), male sex (P<.001), and rural location (P=.007) were
      predictive of higher Medicare reimbursement. CONCLUSIONS: The billing of
      technical services, with their high capital and labor overhead requirements,
      limits any comparison in reimbursement between individual radiation oncologists
      or between radiation oncologists and other specialists. Male sex and rural
      practice location are independent predictors of higher total Medicare
      reimbursements.

PMID- 27026307
TI  - Real-Time 3D Image Guidance Using a Standard LINAC: Measured Motion, Accuracy,
      and Precision of the First Prospective Clinical Trial of Kilovoltage
      Intrafraction Monitoring-Guided Gating for Prostate Cancer Radiation Therapy.
AB  - PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a new real-time 3
      dimensional image guidance method. Unlike previous real-time image guidance
      methods, KIM uses a standard linear accelerator without any additional equipment
      needed. The first prospective clinical trial of KIM is underway for prostate
      cancer radiation therapy. In this paper we report on the measured motion accuracy
      and precision using real-time KIM-guided gating. METHODS AND MATERIALS: Imaging
      and motion information from the first 200 fractions from 6 patient prostate
      cancer radiation therapy volumetric modulated arc therapy treatments were
      analyzed. A 3-mm/5-second action threshold was used to trigger a gating event
      where the beam is paused and the couch position adjusted to realign the prostate
      to the treatment isocenter. To quantify the in vivo accuracy and precision, KIM
      was compared with simultaneously acquired kV/MV triangulation for 187 fractions.
      RESULTS: KIM was successfully used in 197 of 200 fractions. Gating events
      occurred in 29 fractions (14.5%). In these 29 fractions, the percentage of beam
      on time, the prostate displacement was >3 mm from the isocenter position, reduced
      from 73% without KIM to 24% with KIM-guided gating. Displacements >5 mm were
      reduced from 16% without KIM to 0% with KIM. The KIM accuracy was measured at
      <0.3 mm in all 3 dimensions. The KIM precision was <0.6 mm in all 3 dimensions.
      CONCLUSIONS: Clinical implementation of real-time KIM image guidance combined
      with gating for prostate cancer eliminates large prostate displacements during
      treatment delivery. Both in vivo KIM accuracy and precision are well below 1 mm.

PMID- 27026308
TI  - Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (<=70
      Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of
      Localized Muscle-Invasive Bladder Cancer.
AB  - PURPOSE: Image guided adaptive radiation therapy offers individualized solutions
      to improve target coverage and reduce normal tissue irradiation, allowing the
      opportunity to increase the radiation tumor dose and spare normal bladder tissue.
      METHODS AND MATERIALS: A library of 3 intensity modulated radiation therapy plans
      were created (small, medium, and large) from planning computed tomography (CT)
      scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the
      tumor to 70 Gy in 32 fractions. A "plan of the day" approach was used for
      treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly
      to assess intrafraction filling and coverage. RESULTS: A total of 18 patients
      completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy.
      Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose
      of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A
      total of 734 CBCT scans were evaluated. Small, medium, and large plans were used
      in 36%, 48%, and 16% of cases, respectively. The mean +/- standard deviation rate
      of intrafraction filling at the start of treatment (ie, week 1) was 4.0 +/- 4.8
      mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1
      +/- 1.6 mL/min (range 0.01-7.5; P=.002). The mean D98 (dose received by 98%
      volume) of the tumor boost and bladder as assessed on the post-treatment CBCT
      scan was 97.07% +/- 2.10% (range 89.0%-104%) and 99.97% +/- 2.62% (range 96.4%
      112.0%). At a median follow-up period of 19 months (range 4-33), no muscle
      invasive recurrences had developed. Two patients experienced late toxicity (both
      grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation
      therapy. CONCLUSIONS: Image guided adaptive radiation therapy using intensity
      modulated radiation therapy to deliver a simultaneous integrated tumor boost to
      70 Gy is feasible, with acceptable toxicity, and will be evaluated in a
      randomized trial.

PMID- 27026309
TI  - Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer:
      Implications for Adjuvant Radiation Therapy.
AB  - PURPOSE: In patients with muscle-invasive bladder cancer, local-regional failure
      (LF) has been reported to occur in up to 20% of patients following radical
      cystectomy. The goals of this study were to describe patterns of LF, as well as
      assess factors associated with LF in a cohort of patients with pT3-4 bladder
      cancer. This information may have implications towards the use of adjuvant
      radiation therapy. METHODS AND MATERIALS: Patients with pathologic T3-4 N0-1
      bladder cancer were examined from an institutional radical cystectomy database.
      Preoperative demographics and pathologic characteristics were examined. Outcomes
      included overall survival and LF. Local-regional failures were defined using
      follow-up imaging reports and scans, and the locations of LF were characterized.
      Variables were tested by univariate and multivariate analysis for association
      with LF and overall survival. RESULTS: A total of 334 patients had pT3-4 and N0-1
      disease after radical cystectomy and bilateral pelvic lymph node dissection. Of
      these, 46% received perioperative chemotherapy. The median age was 71 years old,
      and median follow-up was 11 months. On univariate analysis, margin status, pT
      stage, and pN stage, were all associated with LF (P<.05), however, on
      multivariate analysis, only pT and pN stages were significantly associated with
      LF (P<.05). Three strata of risk were defined, including low-risk patients with
      pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high
      risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%,
      and 72%, respectively. The most common sites of pelvic relapse included the
      external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably,
      34% of patients with LF had local-regional only disease at the time of
      recurrence. CONCLUSIONS: Patients with pT4 or N1 disease have a 2-year risk of LF
      that exceeds 30%. These patients may be the most likely to benefit from local
      adjuvant therapies.

PMID- 27026310
TI  - Adjuvant Radiation for Locally Advanced Bladder Cancer? A Question Worth Asking.

PMID- 27026311
TI  - Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry
      Based SABR in Prostate Cancer.
AB  - PURPOSE: This study identified predictors of high-grade late hematochezia (HH)
      following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR).
      METHODS AND MATERIALS: Hematochezia data for 258 patients who received 35 to 40
      Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was
      retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia
      needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma
      coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood
      transfusion, or a course of hyperbaric oxygen was grade 3 and development of
      visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed
      using univariate and multivariate analyses. Receiver operating characteristic
      (ROC) curve analysis and recursive partitioning analysis were used to determine
      clinically valid cut-off points and identify risk groups, respectively. RESULTS:
      HH was observed in 19.4%, grade >=3 toxicity in 3.1%. Median follow-up was 29.7
      months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7
      months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was
      4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning
      target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to
      prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC
      analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong
      predictor of HH with an area under the curve of 0.65. In multivariate analysis,
      rectal V38 (>=2.0 cm(3); odds ratio [OR]: 4.7); use of anticoagulants in the
      follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the
      strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0
      cm(3), and use of anticoagulants or rectal V38 >= 2.0 cm(3) plus 1 other risk
      factor resulted in an HH risk of >30%. CONCLUSIONS: Rectal V38 and 2 clinical
      factors were strong predictors of HH following 5-fraction SABR. Planning
      constraints should keep rectal V38 below 2.0 cm(3).

PMID- 27026312
TI  - Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal
      Cancer Patients After Preoperative Chemoradiation Therapy.
AB  - PURPOSE/OBJECTIVE(S): To quantify ensuing bone marrow (BM) suppression during
      postoperative chemotherapy resulting from preoperative chemoradiation (CRT)
      therapy for rectal cancer. METHODS AND MATERIALS: We retrospectively evaluated 35
      patients treated with preoperative CRT followed by postoperative 5-Fluorouracil
      and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic
      bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and
      lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and
      percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The
      Wilcoxon signed rank tests evaluated the differences in absolute hematologic
      nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated
      the association between dosimetric parameters and >= grade 3 hematologic toxicity
      (HT3) and hematologic event (HE) defined as >= grade 2 HT and a dose reduction in
      OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine
      optimal threshold values leading to HT3. RESULTS: During OxF chemotherapy, 40.0%
      (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE,
      respectively. On multivariable logistic regression, increasing pelvic mean dose
      (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM
      V25, and LPBM-V40 were significantly associated with HT3 and/or HE during
      postoperative chemotherapy. Exceeding >=36.6 Gy to the PMD and >=32.6 Gy to the
      LPMD strongly correlated with causing HT3 during postoperative chemotherapy.
      CONCLUSIONS: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic
      BM, which are demonstrable during adjuvant OxF. Sparing of the BM during
      preoperative CRT can aid in reducing significant hematologic adverse events and
      aid in tolerance of postoperative chemotherapy.

PMID- 27026313
TI  - Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer
      Survivors.
AB  - PURPOSE: To conduct a large, population-based study on cardiovascular disease
      (CVD) in breast cancer (BC) survivors treated in 1989 or later. METHODS AND
      MATERIALS: A large, population-based cohort comprising 70,230 surgically treated
      stage I to III BC patients diagnosed before age 75 years between 1989 and 2005
      was linked with population-based registries for CVD. Cardiovascular disease risks
      were compared with the general population, and within the cohort using competing
      risk analyses. RESULTS: Compared with the general Dutch population, BC patients
      had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95%
      confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was
      more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided
      radiation therapy after mastectomy increased the risk of any cardiovascular event
      compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI
      1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36).
      Radiation-associated risks were found for not only ischemic heart disease, but
      also for valvular heart disease and congestive heart failure (CHF). Risks were
      more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07
      2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus
      right-sided radiation therapy after wide local excision did not increase the risk
      of all CVD combined, yet an increased ischemic heart disease risk was found (sHR
      1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy
      information showed an increased CVD risk for left-sided chest wall irradiation
      alone, left-sided breast irradiation alone, and internal mammary chain field
      irradiation, all compared with right-sided breast irradiation alone. Compared
      with patients not treated with chemotherapy, chemotherapy used >=1997 (ie,
      anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00
      1.83). CONCLUSION: Radiation therapy regimens used in BC treatment between 1989
      and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens
      increased the risk of CHF.

PMID- 27026314
TI  - Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to
      Radiation Therapy.
AB  - PURPOSE: This study aimed to estimate the treatment outcome of nasopharyngeal
      cancer (NPC) across the world and its correlation with access to radiation
      therapy (RT). METHODS AND MATERIALS: The age-standardized mortality (ASM) and age
      standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized,
      and [1-(ASM/ASI)] was computed to give the proxy relative survival (RS). Data
      from the International Atomic Energy Agency (IAEA) and the World Bank were used
      to assess the availability of RT in surrogate terms: the number of RT equipment
      units and radiation oncologists per million population. RESULTS: A total of 112
      countries with complete valid data were analyzed, and the proxy RS varied widely
      from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and
      Poor outcome groups on the basis of their proxy RS (<45%, 45%-55%, and >55%).
      Eighty percent of new cases occurred in the Poor outcome group. Univariable
      linear regression showed a significant correlation between outcome and the
      availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per
      unit increase in RT equipment and oncologist per million population,
      respectively. The median number of RT equipment units per million population
      increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the
      Good outcome groups, and the corresponding number of oncologists increased from
      1.1 to 3.3 to 7.1 (P<.001). CONCLUSIONS: Nasopharyngeal cancer is a highly
      treatable disease, but the outcome varies widely across the world. The current
      study shows a significant correlation between survival and access to RT based on
      available surrogate indicators. However, the possible reasons for poor outcome
      are likely to be multifactorial and complex. Concerted international efforts are
      needed not only to address the fundamental requirement for adequate RT access but
      also to obtain more comprehensive and accurate data for research to improve
      cancer outcome.

PMID- 27026315
TI  - Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and
      Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma.
AB  - PURPOSE: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may
      be complicated with radiation-induced brain necrosis (RN), resulting in
      deteriorated cognitive function. However, the underlying mechanism of this
      phenomenon remains unclear. This study attempts to elucidate the association
      between cerebral microbleeds (CMBs) and radiation necrosis and cognitive
      dysfunction in NPC patients treated with radiation therapy. METHODS AND
      MATERIALS: This cross-sectional study included 106 NPC patients who were exposed
      to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients
      without discernable intracranial pathology were included as the control group.
      CMBs were confirmed using susceptibility-weighted magnetic resonance imaging.
      Cognitive function was accessed using Montreal Cognitive Assessment. Patients
      with a total score below 26 were defined as cognitively dysfunction. RESULTS:
      Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non
      RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control
      group had CMBs. In patients with a history of radiation therapy, CMBs most
      commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%).
      Patients with RN had more temporal CMBs than those in the non-RN group (37.7 +/-
      51.9 vs 3.8 +/- 12.6, respectively; P<.001). The number of temporal lobe CMBs was
      predictive for larger volume of brain necrosis (P<.001) in multivariate linear
      regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN
      patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001).
      After adjusting for age, sex, education, period after radiation therapy, CMBs in
      other lobes, and RN volume, the number of temporal CMBs remained an independent
      risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence
      interval [CI]: 1.01-1.04; P=.003). CONCLUSIONS: CMBs is a common radiological
      manifestation in NPC patients with RN. The number of temporal CMBs is
      independently associated with increased likelihood of cognitive dysfunction in
      patients with RN.

PMID- 27026316
TI  - Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas:
      A Systematic Review and Meta-analysis.
AB  - PURPOSE: To evaluate the survival impact of postoperative radiation therapy
      (PORT) in stage II to IV thymomas, using systematic review and meta-analysis.
      METHODS AND MATERIALS: A database search was conducted with EMBASE, PubMed, Web
      of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic
      carcinomas were excluded, and studies comparing overall survival (OS) with and
      without PORT in thymomas were included. The hazard ratios (HRs) of OS were
      extracted, and a random-effects model was used in the pooled analysis. RESULTS:
      Seven retrospective series with a total of 1724 patients were included and
      analyzed. Almost all of the patients underwent macroscopically complete
      resection, and thymoma histology was confirmed by the World Health Organization
      criteria. In the overall analysis of stage II to IV thymomas, OS was not altered
      with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08).
      Although PORT was not associated with survival difference in Masaoka stage II
      disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition
      of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40
      0.99). Significant heterogeneity and publication bias were not found in the
      analyses. CONCLUSIONS: From the present meta-analysis of sole primary thymomas,
      we suggest the potential OS benefit of PORT in locally advanced tumors with
      macroscopically complete resection, but not in stage II disease. Further
      investigations with sufficient survival data are needed to establish detailed
      treatment indications.

PMID- 27026317
TI  - Subsecond and Submillimeter Resolution Positional Verification for Stereotactic
      Irradiation of Spinal Lesions.
AB  - PURPOSE: Spine stereotactic body radiation therapy (SBRT) requires highly
      accurate positioning. We report our experience with markerless template matching
      and triangulation of kilovoltage images routinely acquired during spine SBRT, to
      determine spine position. METHODS AND MATERIALS: Kilovoltage images, continuously
      acquired at 7, 11 or 15 frames/s during volumetric modulated spine SBRT of 18
      patients, consisting of 93 fluoroscopy datasets (1 dataset/arc), were analyzed
      off-line. Four patients were immobilized in a head/neck mask, 14 had no
      immobilization. Two-dimensional (2D) templates were created for each gantry angle
      from planning computed tomography data and registered to prefiltered kilovoltage
      images to determine 2D shifts between actual and planned spine position.
      Registrations were considered valid if the normalized cross correlation score was
      >=0.15. Multiple registrations were triangulated to determine 3D position. For
      each spine position dataset, average positional offset and standard deviation
      were calculated. To verify the accuracy and precision of the technique, mean
      positional offset and standard deviation for twenty stationary phantom datasets
      with different baseline shifts were measured. RESULTS: For the phantom, average
      standard deviations were 0.18 mm for left-right (LR), 0.17 mm for superior
      inferior (SI), and 0.23 mm for the anterior-posterior (AP) direction. Maximum
      difference in average detected and applied shift was 0.09 mm. For the 93 clinical
      datasets, the percentage of valid matched frames was, on average, 90.7% (range:
      49.9-96.1%) per dataset. Average standard deviations for all datasets were 0.28,
      0.19, and 0.28 mm for LR, SI, and AP, respectively. Spine position offsets were,
      on average, -0.05 (range: -1.58 to 2.18), -0.04 (range: -3.56 to 0.82), and -0.03
      mm (range: -1.16 to 1.51), respectively. Average positional deviation was <1 mm
      in all directions in 92% of the arcs. CONCLUSIONS: Template matching and
      triangulation using kilovoltage images acquired during irradiation allows spine
      position detection with submillimeter accuracy at subsecond intervals. Although
      the majority of patients were not immobilized, most vertebrae were stable at the
      sub-mm level during spine SBRT delivery.

PMID- 27026318
TI  - Effects of Aging on Hippocampal Neurogenesis After Irradiation.
AB  - PURPOSE: To assess the influence of aging on hippocampal neuronal development
      after irradiation (IR). METHODS AND MATERIALS: Male mice, 2, 4, 6, 12, and 18
      months of age, were given a single dose of 0 or 5 Gy of IR. A bromodeoxyuridine
      (BrdU) incorporation study was used to label newborn cells. Neural progenitors,
      newborn neurons, and microglia in dentate gyrus (DG) were identified by
      phenotypic markers, and their numbers were quantified by nonbiased stereology 9
      weeks after IR. RESULTS: BrdU-positive or newborn cells in DG decreased with
      aging and after IR. The number of neuroblasts and newborn neurons decreased with
      aging, and a further significant reduction was observed after IR. Total type 1
      cells (the putative neural stem cells), and newborn type 1 cells decreased with
      aging, and further reduction in total type 1 cells was observed after IR. Aging
      associated activation of microglia in hippocampus was enhanced after IR.
      CONCLUSIONS: The aging-associated decline in hippocampal neurogenesis was further
      inhibited after IR. Ablation of neural progenitors and activation of microglia
      may contribute to the inhibition of neuronal development after IR across all
      ages.

PMID- 27026319
TI  - Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer
      Stem Cells Depends on Human Papillomavirus Status.
AB  - PURPOSE: To test the hypothesis that the radiation response of cancer stem cells
      (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck
      squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation
      response of the bulk tumor populations, that radiation therapy (RT) can
      dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced
      dedifferentiation depends on the HPV status. METHODS AND MATERIALS: Records of a
      cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated
      with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell
      lines expressing a reporter for CSCs, we characterized HPV-positive and HPV
      negative lines via flow cytometry, sphere-forming capacity assays in vitro, and
      limiting dilution assays in vivo. Non-CSCs were treated with different doses of
      radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via
      flow cytometry and quantitative reverse transcription-polymerase chain reaction
      for re-expression of reprogramming factors. RESULTS: Patients with HPV-positive
      tumors have superior overall survival and local-regional control. Human
      papillomavirus-positive HNSCC cell lines have lower numbers of CSCs, which
      inversely correlates with radiosensitivity. Human papillomavirus-negative HNSCC
      cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non
      CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation
      compared with HPV-positive lines, and RT induced re-expression of Yamanaka
      reprogramming factors. CONCLUSIONS: Supporting the favorable prognosis of HPV
      positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of
      CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced
      dedifferentiation depends on the HPV status of the tumor.

PMID- 27026320
TI  - Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation
      Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.
AB  - PURPOSE: To determine how low-dose ionizing radiation (LDIR) regulates B lympho
      proliferation and its molecular mechanism related with Ikaros, transcription
      factor. METHODS AND MATERIALS: Splenocytes and IM-9 cells were uniformly
      irradiated with various doses of a (137)Cs gamma-source, and cell proliferation
      was analyzed. To determine the LDIR-specific phosphorylation of Ikaros,
      immunoprecipitation and Western blot analysis were performed. To investigate the
      physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at
      phosphorylation sites were generated, and cell cycle analysis was performed.
      RESULTS: First, we found that LDIR enhances B lymphoblast proliferation in an
      Ikaros-dependent manner. Moreover, we found that LDIR elevates the
      phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and
      AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating
      DNA binding activity of Ikaros via specific phosphorylation. Finally, we
      identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed
      that the Ikaros phosphorylations at these sites control Ikaros's ability to
      regulate G1/S cell cycle progression. CONCLUSION: Low-dose ionizing radiation
      specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate
      cell cycle progression in B lymphoblast.

PMID- 27026321
TI  - In Regard to Nagata et al.

PMID- 27026322
TI  - In Regard to Bruner et al.

PMID- 27026323
TI  - In Regard to Ahmed et al.

PMID- 27026324
TI  - In Reply to Ye et al.

PMID- 27026325
TI  - In Reply to Leung.

PMID- 27026326
TI  - In Regard to Canal et al.

PMID- 27026329
TI  - Measuring muscle and bone in individuals with neurologic impairment; lessons
      learned about participant selection and pQCT scan acquisition and analysis.
AB  - Peripheral quantitative computed tomography (pQCT) can be used to examine bone
      strength outcomes and muscle size and fatty infiltration. Our research team and
      others have used it to examine bone loss after spinal cord injury (SCI). However,
      the high prevalence of restricted lower extremity range of motion, spasticity,
      edema, excessive muscle atrophy, or severe osteoporosis necessitates changes to
      standard protocols for screening, positioning during scan acquisition, and
      analysis methods. This manuscript outlines the challenges that we experienced
      using pQCT in individuals with SCI, and provides solutions, ones that may also be
      applicable when using pQCT in individuals with other chronic conditions or in
      older adults. Suggestions for participant screening, positioning individuals for
      scanning while in a wheelchair, scan site selection, need for attendant
      assistance, and considerations in the presence of secondary complications, such
      as contracture, spasticity, and paralysis, are presented. In the presence of very
      low bone mineral density or severe muscle atrophy, the default analysis modes
      provided by the manufacturer may not provide valid estimates of bone or muscle
      indices; we propose alternates. We have used watershed segmentation methods to
      determine muscle size and density based on lower precision error compared to
      threshold-based edge-detection segmentation, particularly for adults with SCI,
      where more fatty infiltration was present. By presenting our "lessons learned,"
      we hope to reduce the learning curve for researchers using pQCT in the future.

PMID- 27026330
TI  - The role of biochemical of bone turnover markers in osteoporosis and metabolic
      bone disease: a consensus paper of the Belgian Bone Club.
AB  - The exact role of biochemical markers of bone turnover in the management of
      metabolic bone diseases remains a topic of controversy. In this consensus paper,
      the Belgian Bone Club aimed to provide a state of the art on the use of these
      biomarkers in different clinical or physiological situations like in
      postmenopausal women, osteoporosis in men, in elderly patients, in patients
      suffering from bone metastasis, in patients with chronic renal failure, in
      pregnant or lactating women, in intensive care patients, and in diabetics. We
      also gave our considerations on the analytical issues linked to the use of these
      biomarkers, on potential new emerging biomarkers, and on the use of bone turnover
      biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

PMID- 27026331
TI  - 25-Hydroxycholecalciferol response to single oral cholecalciferol loading in the
      normal weight, overweight, and obese.
AB  - After a single cholecalciferol load, peak serum 25-hydroxycholecalciferol (25OHD)
      is lower in individuals with a higher body mass index (BMI), probably due to it
      being distributed in a greater volume. Its subsequent disappearance from the
      serum is slower the higher the individual's BMI, probably due to the combination
      of a larger body volume and a slower release into the circulation of vitamin D
      stored in adipose tissue. INTRODUCTION: The aim of the study is to examine 25
      hydroxycholecalciferol (25OHD) response to a single oral load of cholecalciferol
      in the normal weight, overweight, and obese. METHODS: We considered 55 healthy
      women aged from 25 to 67 years (mean +/- SD, 50.8 +/- 9.5) with a BMI ranging
      from 18.7 to 42 kg/m(2) (mean +/- SD, 27.1 +/- 6.0). The sample was divided into
      three groups by BMI: 20 were normal weight (BMI <= 25 kg/m(2)), 21 overweight
      (25.1 <= BMI <= 29.9 kg/ m(2)), and 14 obese (BMI >= 30 kg/m(2)). Each subject
      was given 300,000 IU of cholecalciferol orally during lunch. A fasting blood test
      was obtained before cholecalciferol loading and then 7, 30, and 90 days
      afterwards to measure serum 25OHD, 1,25 dihydroxyvitamin D [1,25 (OH)2D],
      parathyroid hormone (PTH), calcium (Ca), and phosphorus (P). Participants'
      absolute fat mass was measured using dual energy X-ray absorptiometry (DEXA).
      RESULTS: The fat mass of the normal weight subjects was significantly lower than
      that of the overweight, which in turn was lower than that of the obese
      participants. Serum 25OHD levels increased significantly in all groups, peaking 1
      week after the cholecalciferol load. Peak serum 25OHD levels were lower the
      higher the individuals' BMI. After peaking, the 25OHD levels gradually decreased,
      following a significantly different trend in the three groups. The slope was
      similar for the overweight and obese, declining significantly more slowly than in
      the normal weight group. In the sample as a whole, there was a weakly significant
      negative correlation between fat mass and baseline 25OHD level, while this
      correlation became strongly significant at all time points after cholecalciferol
      loading. CONCLUSIONS: The lower peak 25OHD levels seen in the obese and
      overweight is probably due to the cholecalciferol load being distributed in a
      larger body volume. The longer persistence of 25OHD in their serum could be due
      to both their larger body volume and a slower release into the circulation of the
      vitamin D stored in their adipose tissue.

PMID- 27026332
TI  - Depression risk in female patients with osteoporosis in primary care practices in
      Germany.
AB  - Thirty-five thousand four hundred eighty-three female osteoporosis patients were
      compared with 35,483 patients without osteoporosis regarding the incidence of
      depression. The risk of depression is significantly increased for patients with
      osteoporosis compared with patients without osteoporosis in primary care
      practices within Germany. INTRODUCTION: The objectives of the present study were
      to analyze the incidence of depression in German female patients with
      osteoporosis and to evaluate the risk factors for depression diagnosis within
      this patient population. METHODS: This study was a retrospective database
      analysis conducted in Germany utilizing the Disease Analyzer(r) Database (IMS
      Health, Germany). The study population included 70,966 patients between 40 and 80
      years of age from 1072 primary care practices. The observation period was between
      2004 and 2013. Follow-up duration was 5 years and was completed in April 2015. A
      total of 35,483 osteoporosis patients were selected after applying exclusion
      criteria, and 35,483 controls were chosen and then matched (1:1) to osteoporosis
      patients based on age, sex, health insurance coverage, depression diagnosis in
      the past, and follow-up duration after index date. The analyses of depression
      free survival were carried out using Kaplan-Meier curves and log-rank tests. Cox
      proportional hazards models (dependent variable: depression) were used to adjust
      for confounders. RESULTS: Depression diagnoses were presented in 33.0 % of the
      osteoporosis group and 22.7 % of the control group after the 5-year follow-up (p
      < 0.001). Dementia, cancer, heart failure, coronary heart disease, and diabetes
      were associated with a higher risk of developing depression (p < 0.001). Private
      health insurance was associated with a lower risk of depression. There was no
      significant effect of fractures on depression risk. CONCLUSION: The risk of
      depression is significantly increased for patients with osteoporosis in primary
      care practices within Germany.

PMID- 27026333
TI  - Uncertain effects of calcium and vitamin D supplementation on fracture risk
      reduction.

PMID- 27026334
TI  - Clinical and radiographic evaluation of effect of risedronate 5 mg as an adjunct
      to treatment of chronic periodontitis in postmenopausal women (12-month study).
AB  - Bisphosphonates are beneficial to women, after menopause, in treatment of gum
      diseases. In this study, significant improvement in the disease condition was
      found and that no further progress was noted, and no side effects were reported.
      Bisphosphonates can be safely and successfully be used to support oral health
      procedures. INTRODUCTION: The purpose of this study was to evaluate host
      modulating effect of bisphosphonate adjunct with the treatment of chronic
      periodontitis in osteopenic and osteoporotic postmenopausal women. METHODS:
      Twenty-two osteopenic and osteoporotic postmenopausal women with moderate to
      severe chronic periodontitis were selected for the study. On intraoral
      examination, periodontal parameters like probing depth (PD), clinical attachment
      level (CAL), Plaque Index (PI) and Gingival Index (GI) were recorded. Scaling and
      root planing were done. Intraoral periapical X-rays were taken, and alveolar bone
      density (ABD) was measured with cone beam computed tomography (CBCT), and then,
      medications (risedronate 5 mg once daily (OD), calcium citrate 250 mg OD, vitamin
      D 400 IU OD) were given. Patients were recalled for follow-up at 3, 6 and 12
      months. Intraoral periapical (IOPA) X-rays were taken at 6 and 12 months and ABD
      was measured at baseline and 12 months. RESULTS: There was a significant
      improvement in all the parameters. There was an increase of 0.02 +/- 0.001 cm on
      CT scan and 0.38 +/- 0.005 mm on IOPA in bone height over 12 months from
      baseline. Bone density increased by 118.56 +/- 3.251 Hounsfield units (HU). There
      was no progress in the disease, and further bone loss was not noticed. This is in
      correlation with clinical parameters which showed highly significant gain in CAL
      (3.57 +/- 0.234 mm) and reduction in PD (2.20 +/- 0.229 mm) CONCLUSIONS:
      Bisphosphonate therapy as an adjunct to scaling and root planing may have
      significant beneficial clinical effects on the periodontium of postmenopausal
      women with moderate to severe chronic periodontitis.

PMID- 27026335
TI  - Response of bone turnover markers to raloxifene treatment in postmenopausal women
      with osteopenia.
AB  - We used two methods of identifying women who reached the target for raloxifene
      treatment with bone turnover markers. Both approaches identified women that
      responded to treatment but did not fully agree and may be complementary.
      INTRODUCTION: The change in bone turnover markers (BTMs) in response to
      osteoporosis therapy can be assessed by a decrease beyond the least significant
      change (LSC) or below the mean of the reference interval (RI). We compared the
      performance of these two approaches in women treated with raloxifene. METHODS:
      Fifty postmenopausal osteopenic women (age 51-72 years) were randomised to
      raloxifene or no treatment for 2 years. Blood samples were collected for the
      measurement of BTM. The LSC for each marker was calculated from the untreated
      women and the RI obtained from healthy premenopausal women (age 35-40 years).
      Bone mineral density (BMD) was measured at the spine and hip. RESULTS: There was
      a decrease in BTM in response to raloxifene treatment, percentage change at 12
      weeks: C terminal telopeptide of type I collagen (CTX) -39 % (95 % CI -48 to -28)
      and N terminal propeptide of type I procollagen (PINP) -32 % (95 % CI -40 to -23)
      P < 0.001. The proportion of women classified as responding to treatment using
      LSC at 12 weeks was as follows: CTX 38 % and PINP 52 % and at 48 weeks CTX 60 %
      and PINP 65 %. For the RI approach, the proportion of women classified as
      responding to treatment at 12 weeks was CTX and PINP 38 % and at 48 weeks CTX 40
      % and PINP 45 %. There was a significant difference in the change in spine BMD in
      the raloxifene-treated group compared to the no-treatment group at week 48:
      difference 0.031 g/cm(2) (95 % CI 0.016 to 0.046, P < 0.001). CONCLUSIONS: The
      two approaches identified women that reached the target for treatment using BTM.
      Both LSC and RI criteria appear useful in identifying treatment response, but the
      two approaches do not fully overlap and may be complementary.

PMID- 27026336
TI  - Air Pollution Exposure During Pregnancy and Fetal Markers of Metabolic function:
      The MIREC Study.
AB  - Previous evidence suggests that exposure to outdoor air pollution during
      pregnancy could alter fetal metabolic function, which could increase the risk of
      obesity in childhood. However, to our knowledge, no epidemiologic study has
      investigated the association between prenatal exposure to air pollution and
      indicators of fetal metabolic function. We investigated the association between
      maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic
      diameter <=2.5 um) and umbilical cord blood leptin and adiponectin levels with
      mixed-effects linear regression models among 1,257 mother-infant pairs from the
      Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in
      Canada (2008-2011). We observed that an interquartile-range increase in average
      exposure to fine particulate matter (3.2 ug/m(3)) during pregnancy was associated
      with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We
      also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per
      interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts
      per billion) during pregnancy. Significant associations were seen between air
      pollution markers and cord blood leptin levels in models that adjusted for birth
      weight z score but not in models that did not adjust for birth weight z score.
      The roles of prenatal exposure to air pollution and fetal metabolic function in
      the potential development of childhood obesity should be further explored.

PMID- 27026337
TI  - Can Community Social Cohesion Prevent Posttraumatic Stress Disorder in the
      Aftermath of a Disaster? A Natural Experiment From the 2011 Tohoku Earthquake and
      Tsunami.
AB  - In the aftermath of a disaster, the risk of posttraumatic stress disorder (PTSD)
      is high. We sought to examine whether the predisaster level of community social
      cohesion was associated with a lower risk of PTSD after the earthquake and
      tsunami in Tohoku, Japan, on March 11, 2011. The baseline for our natural
      experiment was established in a survey of older community-dwelling adults who
      lived 80 kilometers west of the epicenter 7 months before the earthquake and
      tsunami. A follow-up survey was conducted approximately 2.5 years after the
      disaster. We used a spatial Durbin model to examine the association of community
      level social cohesion with the individual risk of PTSD. Among our analytic sample
      (n = 3,567), 11.4% of respondents reported severe PTSD symptoms. In the spatial
      Durbin model, individual- and community-level social cohesion before the disaster
      were significantly associated with lower risks of PTSD symptoms (odds ratio =
      0.87, 95% confidence interval: 0.77, 0.98 and odds ratio = 0.75, 95% confidence
      interval: 0.63, 0.90, respectively), even after adjustment for depression
      symptoms at baseline and experiences during the disaster (including loss of loved
      ones, housing damage, and interruption of access to health care). Community-level
      social cohesion strengthens the resilience of community residents in the
      aftermath of a disaster.

PMID- 27026338
TI  - Social and clinical attributes of patients who restart antiretroviral therapy in
      central and Copperbelt provinces, Zambia: a retrospective longitudinal study.
AB  - BACKGROUND: About 30% of the patients initiated on antiretroviral therapy in
      Zambia default treatment. Some of these patients later restart treatment;
      however, the characteristics of these patients have not been well described and
      documented. The aim of this study was to describe and document the socio
      demographic and clinical characteristics of patients who default and restart
      antiretroviral therapy, and to determine the socio-demographic characteristics
      associated with CD4 count response at 6 and 24 months of restarting
      antiretroviral therapy. METHODS: A longitudinal retrospective analysis was
      performed on data from 535 adult patients restarting antiretroviral therapy in
      2009 and 2010 at five antiretroviral therapy centres in Copperbelt and Central
      provinces of Zambia. To determine the association between the socio-demographic
      characteristics and CD4 cell count, quantile regression models were used.
      RESULTS: Older age above 45 years was associated with a significantly lower CD4
      cell response by 38.1 cells/mm(3) (95% Confidence interval [CI]: -109.4 to -0.2)
      compared to the younger age (15-29 years). Patients in formal employment
      (Adjusted Coefficient [AC] 29.5, 95% CI: 22.8 to 81.1) and self-employment (AC
      48.1, 95% CI: 18.6 to 77.4) gained significantly higher CD4 cells than those
      unemployed. In addition, baseline CD4 count, type of treatment, WHO staging,
      total duration on treatment and duration lost to follow-up were found to be
      strong predictors of CD4 cell count at 6 and 24 months after restarting
      antiretroviral therapy treatment. CONCLUSION: Age and occupation were the only
      socio-demographic characteristics predicting CD4 count in the patients at 6
      months after restarting antiretroviral therapy after adjusting for other
      confounding clinical variables.

PMID- 27026339
TI  - Population Pharmacokinetics Modeling of Inhaled Umeclidinium for Adult Patients
      with Asthma.
AB  - BACKGROUND: Umeclidinium (UMEC; a long-acting anti-muscarinic) in combination
      with fluticasone furoate (an inhaled corticosteroid) is in development for asthma
      treatment. This secondary analysis aimed to develop a population pharmacokinetic
      model characterizing UMEC in adults with asthma, and evaluated the impact of
      covariates on pharmacokinetic parameters. METHODS: Plasma concentration data from
      study NCT01641692 (assessing once-daily UMEC 15.6, 31.25, 62.5, 125, and 250 mcg,
      twice daily UMEC 15.6 and 31.25 mcg, and placebo) were analyzed using non-linear
      mixed-effect modeling in NONMEM(r). Full likelihood, including observed data and
      data below the quantification limit (treated as censored), was maximized. Study
      endpoints were population pharmacokinetics (including apparent inhaled clearance
      [CL/F] and apparent distribution volume in the central compartment [V c/F]) and
      derived pharmacokinetic parameters (area under the concentration-time curve [AUC]
      and maximum concentration [C max] at steady-state). RESULTS: In total, 128
      patients provided 3757 data points. The pharmacokinetics of UMEC were best
      described using a two-compartment model with intravenous bolus input, due to fast
      absorption following inhalation. CL/F was 257 L/h and V c/F was 804 L. Creatinine
      clearance was a significant covariate for CL/F, as were age and body weight for V
      c/F. AUC and C max increased with increasing UMEC dose (once-daily 15.6-250 mcg:
      AUC0-24 median: 64.7-863 pg h/mL; C max median: 10.6-256 pg/mL). CONCLUSION: The
      final population pharmacokinetic model adequately described the data,
      demonstrating minimal creatinine clearance, age, and body weight effects on
      overall plasma UMEC pharmacokinetics and systemic exposure.

PMID- 27026340
TI  - Effects of Bisphosphonates and Calcium plus Vitamin-D Supplements on Cognitive
      Function in Postmenopausal OsteoporosisS.
AB  - BACKGROUND: Postmenopausal osteoporosis has been linked to accelerated cognitive
      decline; however, little is known about the effects of medical treatment on
      cognitive functions. MATERIAL AND METHODS: In this prospective study, we
      evaluated the effects of bisphosphonate treatment and calcium plus vitamin D
      supplementation on cognitive functions in 45 women with postmenopausal
      osteoporosis who were started on medical treatment. The medications included
      alendronate, zoledronic acid, risedronate, or ibandronic acid along with a low or
      high dose of calcium plus vitamin D supplements. The cognitive function was
      assessed by the mini-mental state examination (MMSE) test. All subjects underwent
      bone mineral density (BMD) measurement via dual-energy X-ray absorptiometry at
      baseline and at study completion. RESULTS: The mean T-score improved
      significantly at 1 year, except for neck of the femur area. The mean MMSE score
      did not change significantly at 12 months (26.40 +/- 2.07 vs. 26.48 +/- 2.07; p =
      0.513), with no difference among bisphosphonates combined with calcium plus
      vitamin D. Higher dose (1200 mg/800 U/day) of calcium plus vitamin D
      supplementation tended to have a greater improvement as compared with lower dose
      (600 mg/400 U/day) (Delta MMSE: 0.11 +/- 0.72 vs. -0.14 +/- 0.69). CONCLUSIONS:
      Cognitive functions in the women remained unaltered, whereas bone BMD T-scores
      were significantly improved at the 12(th) month after the administration of
      bisphosphonates and calcium plus vitamin D supplements. Higher doses of calcium
      plus vitamin D supplements were likely to have better cognitive effects as
      compared with lower doses.

PMID- 27026341
TI  - Increase of segmental mobility through insertion of a flexible linker in split
      point of firefly luciferase.
AB  - The crystal structure of Photinus pyralis luciferase shows a unique molecular
      architecture consisting of a large N-terminal domain and a small C-terminal
      domain which is separated by a wide cleft. Protein engineering methods attempts
      to design the peptide linkers that make a connection between different protein
      domains or subunits to allow for separating domains and improve kinetics and
      structural features of proteins. In regard to this; introduction of a flexible
      linker at split point of luciferase which has a strong self-association activity,
      may leads to conformational change and improve general flexibility of protein. In
      this study, two flexible linkers in the split point of luciferase are introduced
      in order to test the effect of linker on flexibility of luciferase activity.
      Glycine-rich linkers are introduced into P. pyralis firefly luciferase to make
      two separate mutant enzymes. Enzymatic properties of mutant and native forms were
      measured using luminescence assay. Results show that lengthening of luciferase
      domains through insertion of a flexible linker did not affect bioluminescence
      emission spectra. Also adding linkers do not have remarkable effect on
      thermostability. The Km values of mutants were increased compared to native form,
      indicating lower affinity of mutants toward substrates.

PMID- 27026342
TI  - Improving oral bioavailability of acyclovir using nanoparticulates of thiolated
      xyloglucan.
AB  - Acyclovir a BCS class III drug exhibits poor bioavailability due to limited
      permeability. The intention of this research work was to formulate and
      characterize thiolated xyloglucan polysaccharide nanoparticles (TH-NPs) of
      acyclovir with the purpose of increasing its oral bioavailability. Acyclovir
      loaded TH-NPs were prepared using a cross-linking agent. Interactions of
      formulation excipients were reconnoitered using Fourier transform infrared
      spectroscopy (FT-IR). The formulated nanoparticles were lyophilised by the
      addition of a cryoprotectant and characterized for its particle size, morphology
      and stability and optimized using Box Behnken Design.The optimized TH-NP
      formulation exhibited particle size of 474.4+/-2.01 and an entrapment efficiency
      of 81.57%. A marked enhancement in the mucoadhesion was also observed. In-vivo
      study in a rat model proved that relative bioavailability of acyclovir TH-NPs is
      ~2.575 fold greater than that of the marketed acyclovir drug suspension. 

PMID- 27026343
TI  - VIP protects human retinal microvascular endothelial cells against high glucose
      induced increases in TNF-alpha and enhances RvD1.
AB  - PURPOSE: The purpose of our study was to evaluate the therapeutic effect of VIP
      on human retinal endothelial cells (HREC) under high glucose conditions. Diabetes
      affects almost 250 million people worldwide. Over 40% of diabetics are expected
      to develop diabetic retinopathy, which remains the leading cause of visual
      impairment/blindness. Currently, treatment is limited to late stages of
      retinopathy with no options available for early stages. To this end, the purpose
      of the current study is to evaluate the therapeutic effect of vasoactive
      intestinal peptide (VIP) on HREC under high glucose conditions. METHODS: Primary
      HREC were cultured in normal (5mM) or high (25mM) glucose medium +/- VIP
      treatment. Protein levels of TNF-alpha, resolvin D1 (RvD1), formyl peptide
      receptor 2 (FPR2), G protein-coupled receptor 32 (GPR32), VEGF, and VIP
      receptors, VPAC1 and VPAC2 were measured. RESULTS: High glucose-induced changes
      in TNF-alpha and RvD1 were restored to control levels with VIP treatment. RvD1
      receptors, ALX/FPR2 and GPR32, were partially rescued with VIP treatment. VPAC2
      expression appeared to be the major receptor involved in VIP signaling in HREC,
      as VPAC1 receptor was not detected. In addition, VIP did not induce HREC
      secretion of VEGF under high glucose conditions. CONCLUSIONS: Our results
      demonstrate that VIP's therapeutic effect on HREC, occurs in part, through the
      balance between the pro-inflammatory cytokine, TNF-alpha, and the pro-resolving
      mediator, RvD1. Although VPAC1 is considered the major VIP receptor, VPAC2 is
      predominantly expressed on HREC under both normal and high glucose conditions.

PMID- 27026345
TI  - Gender Differences in Stressors Related to Migration and Acculturation in
      Patients with Psychiatric Disorders and Turkish Migration Background.
AB  - Migration, acculturation, and psychiatric disorders may cause stress and
      adaptation processes differently in men and women, but empirical research is
      scarce. In a retrospective study n = 62 Turkish migrants and n = 62 native German
      inpatients with depressive or anxiety disorders, matched for age, gender, and
      diagnoses, were compared using a 10-item instrument for the assessment of
      migration- and acculturation related stressors (MIGSTR10). Gender differences in
      the prevalence of stressors and in the total sum of stressors were calculated and
      compared between migrants and indigenous patients. Results showed a higher global
      stress level in migrants and in women than in men with migration background.
      Regarding single stressors, the perceived loss of status was significantly more
      prevalent and more pronounced in men than in women (P < 0.05) whereas guilt
      feelings were more severe in women with Turkish migration background compared to
      men (P < 0.05). Gender differences of perceived stress should be taken into
      account in migration and acculturation research.

PMID- 27026346
TI  - Health Care Satisfaction: Effects of Immigration, Acculturation, Language.
AB  - Differences in health care satisfaction can alter patterns of health care
      utilization and so affect health outcomes, but little is known about variation in
      satisfaction in relation to immigration status. Health care satisfaction is
      analyzed with survey data from state public health program patients. Overall
      health care satisfaction is higher for first generation Hispanic immigrants and
      lower among those in the second generation compared to white Americans-consistent
      with the pattern termed the "healthy migrant effect." This pattern is more
      pronounced for Portuguese-speaking immigrants and is not explained by self
      reported health, communication ability or acculturation. Satisfaction with
      specific aspects of health care follows different patterns that may be explained
      by differences in experiences and culture. As anticipated by segmented
      assimilation theory, we find variation in cross-generational patterns of health
      care satisfaction both within and between ethnic groups. This variation indicates
      the importance of distinguishing Portuguese-speakers from Spanish-speakers and of
      taking into account differences in the ways they are able to communicate with
      health care providers as well as differences in their orientations toward health
      care. Our disparate findings with other immigrant groups also reinforce limiting
      expectations of a "healthy migrant effect" to Latinos. Finally, the variable
      influences on different satisfaction measures indicate the importance of
      considering the relative influence of culturally-based orientations and health
      care experiences on the specific outcomes measured, with particular sensitivity
      to acceptance of individualized standards of care.

PMID- 27026347
TI  - Prevalence and risk factors of three curable sexually transmitted infections
      among women in Nairobi, Kenya.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are a major public health
      problem, especially in developing countries. The complications of untreated STIs
      in the female genital tract and their role in adverse pregnancy and perinatal
      outcomes have been well documented. The prevalence of STIs in Kenya among women
      in the general population has not been extensively studied and there is a lack of
      guidelines for screening of non-pregnant women. Knowledge of the prevalence of
      curable STIs among this population can provide a basis for integrating STI
      screening in family planning clinics. METHODS: A cross-sectional study was
      conducted between May and September 2013 at the family planning (FP) clinic at
      Kenyatta National Hospital (KNH) in Nairobi, Kenya. A total of 261 participants
      aged 18-49 years were enrolled; with data from 249 participants being analysed.
      An interviewer-administered questionnaire was used to gather socio-demographic
      data and assess for risk factors. Each participant was screened for Trichomonas
      vaginalis (TV) by wet mount microscopy; Neisseria gonorrhoeae (GC) by culture and
      Chlamydia trachomatis (CT) by PCR. RESULTS: The prevalence of CT was 13%
      (33/249), TV 0.4% (1/249) and GC 0% (0/249). All the infected women reported
      having had only one sexual partner in the previous 1 year. The age group
      prevalence for CT was highest in the 25-29 years age group (21%). The syndromic
      approach to the management of STIs showed a low specificity (vaginal discharge,
      65.7%; lower abdominal pain, 60.6%) and positive predictive value (vaginal
      discharge, 14%; lower abdominal pain, 11.5%) for the two commonly used symptoms
      when compared to the gold standard of CT PCR. CONCLUSION: A high prevalence of CT
      was identified among women attending the FP Clinic at KNH. The study reinforces
      the need to implement regular screening for STIs among FP clinic attendants. It
      also reveals the need to review the usage of the syndromic approach for the
      management of STIs.

PMID- 27026349
TI  - Transplantation: BENEFIT of belatacept: kidney transplantation moves forward.

PMID- 27026350
TI  - Genetics: Evolving risks of UMOD variants.

PMID- 27026351
TI  - Acute kidney injury: Improved fuel metabolism protects against AKI.

PMID- 27026348
TI  - Role of TLRs and DAMPs in allograft inflammation and transplant outcomes.
AB  - Graft inflammation impairs the induction of solid organ transplant tolerance and
      enhances acute and chronic rejection. Elucidating the mechanisms by which
      inflammation is induced after organ transplantation could lead to novel
      therapeutics to improve transplant outcomes. In this Review we describe
      endogenous substances--damage-associated molecular patterns (DAMPs)--that are
      released after allograft reperfusion and induce inflammation. We also describe
      innate immune signalling pathways that are activated after solid organ
      transplantation, with a focus on Toll-like receptors (TLRs) and their signal
      adaptor, MYD88. Experimental and clinical studies have yielded a large body of
      evidence that TLRs and MYD88 are instrumental in initiating allograft
      inflammation and promoting the development of acute and chronic rejection.
      Ongoing clinical studies are testing TLR inhibition strategies in solid organ
      transplantation, although avoiding compromising host defence to pathogens is a
      key challenge. Further elucidation of the mechanisms by which sterile
      inflammation is induced, maintained and amplified within the allograft has the
      potential to lead to novel anti-inflammatory treatments that could improve
      outcomes for solid organ transplant recipients.

PMID- 27026352
TI  - Acute kidney injury: Clinical trials in AKI: is the end in sight?

PMID- 27026353
TI  - Striking junior doctors will return to work in emergency, says BMA.

PMID- 27026354
TI  - Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon
      Microscopy of Cleared Mouse Brain.

PMID- 27026357
TI  - Temporal Variation in Physiological Biomarkers in Black Flying-Foxes (Pteropus
      alecto), Australia.
AB  - Bats of the genus Pteropus (Pteropodidae) are recognised as the natural host of
      multiple emerging pathogenic viruses of animal and human health significance,
      including henipaviruses, lyssaviruses and ebolaviruses. Some studies have
      suggested that physiological and ecological factors may be associated with Hendra
      virus infection in flying-foxes in Australia; however, it is essential to
      understand the normal range and seasonal variability of physiological biomarkers
      before seeking physiological associations with infection status. We aimed to
      measure a suite of physiological biomarkers in P. alecto over time to identify
      any seasonal fluctuations and to examine possible associations with life-cycle
      and environmental stressors. We sampled 839 adult P. alecto in the Australian
      state of Queensland over a 12-month period. The adjusted population means of
      every assessed hematologic and biochemical parameter were within the reported
      reference range on every sampling occasion. However, within this range, we
      identified significant temporal variation in these parameters, in urinary
      parameters and body condition, which primarily reflected the normal annual life
      cycle. We found no evident effect of remarkable physiological demands or
      nutritional stress, and no indication of clinical disease driving any parameter
      values outside the normal species reference range. Our findings identify
      underlying temporal physiological changes at the population level that inform
      epidemiological studies and assessment of putative physiological risk factors
      driving Hendra virus infection in P. alecto. More broadly, the findings add to
      the knowledge of Pteropus populations in terms of their relative resistance and
      resilience to emerging infectious disease. 

PMID- 27026359
TI  - Erratum to: A novel vaccinia virus with dual oncolytic and anti-angiogenic
      therapeutic effects against triple-negative breast cancer.

PMID- 27026358
TI  - Perchlorate in Water Supplies: Sources, Exposures, and Health Effects.
AB  - Perchlorate exposure occurs from ingestion of natural or man-made perchlorate in
      food or water. Perchlorate is used in a variety of industrial products including
      missile fuel, fireworks, and fertilizers, and industrial contamination of
      drinking water supplies has occurred in a number of areas. Perchlorate blocks
      iodide uptake into the thyroid and decreases the production of thyroid hormone, a
      critical hormone for metabolism, neurodevelopment, and other physiologic
      functions. Occupational and clinical dosing studies have not identified clear
      adverse effects, but may be limited by small sample sizes, short study durations,
      and the inclusion of mostly healthy adults. Expanding evidence suggests that
      young children, pregnant women, fetuses, and people co-exposed to similarly
      acting agents may be especially susceptible to perchlorate. Given the ubiquitous
      nature of perchlorate exposure, and the importance of thyroid hormone for brain
      development, studying the impact of perchlorate on human health could have far
      reaching public health implications. 

PMID- 27026360
TI  - Synchronous ileal neuroendocrine tumor: diagnosis and treatment. A case report
      and review of the literature.
AB  - INTRODUCTION: The majority of neuroendocrine tumors (NET) are located in the
      gastrointestinal tract (67.5%) and in the bronchopulmonary (25.3%). CASE REPORT:
      CA, female, 42 years old, profuse diarrhea about two months, cramping for
      increased peristalsis, vomiting and weight loss. The patient, diagnosed with
      ileal neuroendocrine tumor, by colonoscopy with biopsy of lesion, therefore came
      in our unit to be subjected to surgical therapy. Plasma assay Chromogranin A was
      performed: 160 ng / ml (nv: 15-100 ng / ml). The patient underwent surgery of
      right hemicolectomy. DISCUSSION: Neuroendocrine tumors although are rare
      diseases, have an increasing impact, probably by virtue of improved diagnostic
      methods. In case of profuse diarrhea should be suspected a neuroendocrine tumor.
      Certainly the diagnosis of certainty is given by histological examination (biopsy
      or resected nodule). CONCLUSION: After surgical excision is necessary to perform
      the follow-up of chromogranin A, and, if not executed, perform nuclear medicine
      examinations such as Octreoscan and PET. KEY-WORDS: Chromogranin A,
      Neuroendocrine tumor, Octreoscan.

PMID- 27026362
TI  - Ligand-Controlled Monoselective C-Aryl Glycoside Synthesis via Palladium
      Catalyzed C-H Functionalization of N-Quinolyl Benzamides with 1-Iodoglycals.
AB  - A monoselective synthesis of aryl-C-Delta(1,2)-glycosides from 1-iodoglycals via
      palladium-catalyzed ortho-C-H activation of N-quinolyl benzamides has been
      developed. An amino acid derivative was used as a crucial ligand to improve the
      yield and monoselectivity of the coupling reaction. The utility of this protocol
      was demonstrated by a concise synthesis of key moieties of some natural products.

PMID- 27026363
TI  - Structural insight in the toppling mechanism of an energy-coupling factor
      transporter.
AB  - Energy-coupling factor (ECF) transporters mediate uptake of micronutrients in
      prokaryotes. The transporters consist of an S-component that binds the
      transported substrate and an ECF module (EcfAA'T) that binds and hydrolyses ATP.
      The mechanism of transport is poorly understood but presumably involves an
      unusual step in which the membrane-embedded S-component topples over to carry the
      substrate across the membrane. In many ECF transporters, the S-component
      dissociates from the ECF module after transport. Subsequently, substrate-bound S
      components out-compete the empty proteins for re-binding to the ECF module in a
      new round of transport. Here we present crystal structures of the folate-specific
      transporter ECF-FolT from Lactobacillus delbrueckii. Interaction of the ECF
      module with FolT stabilizes the toppled state, and simultaneously destroys the
      high-affinity folate-binding site, allowing substrate release into the cytosol.
      We hypothesize that differences in the kinetics of toppling can explain how
      substrate-loaded FolT out-competes apo-FolT for association with the ECF module. 

PMID- 27026361
TI  - Inflammation Models of Depression in Rodents: Relevance to Psychotropic Drug
      Discovery.
AB  - Inflammation and depression are closely inter-related; inflammation induces
      symptoms of depression and, conversely, depressed mood and stress favor an
      inflammatory phenotype. The mechanisms that mediate the ability of inflammation
      to induce symptoms of depression are intensively studied at the preclinical
      level. This review discusses how it has been possible to build animal models of
      inflammation-induced depression based on clinical data and to explore critical
      mechanisms downstream of inflammation. Namely, we focus on the ability of
      inflammation to increase the activity of the tryptophan-degrading enzyme,
      indoleamine 2,3 dioxygenase, which leads to the production of kynurenine and
      downstream neuroactive metabolites. By acting on glutamatergic neurotransmission,
      these neuroactive metabolites play a key role in the development of depression
      like behaviors. An important outcome of the preclinical research on inflammation
      induced depression is the identification of potential novel targets for
      antidepressant treatments, which include targeting the kynurenine system and
      production of downstream metabolites, altering transport of kynurenine into the
      brain, and modulating glutamatergic transmission.

PMID- 27026364
TI  - Enhancing Nephrology Career Interest through the ASN Kidney TREKS Program.
AB  - The Kidney Tutored Research and Education for Kidney Students (TREKS) Program is
      a product of the American Society of Nephrology (ASN) Workforce Committee that
      seeks to connect medical and graduate students to nephrology. This program starts
      with a weeklong camp-like course introducing participants to renal physiology
      through classic and modern experiments. Next, each student is matched with a
      nephrology mentor at his or her home institution to foster a better understanding
      of a nephrology career. Lastly, the students are encouraged to participate in
      scholarly activities and attend the ASN Kidney Week. Now in its third year, with
      a total of 84 participants, survey data suggest early success of the program,
      with a self-reported 40% increased interest in nephrology fellowship and/or
      research careers. In addition, students give high ratings to the course
      components and mentorship pairings. Continued student tracking will be necessary
      to determine the long-term program effect.

PMID- 27026365
TI  - Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study.
AB  - The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a
      single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment
      providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose
      treatment used lowered plasma levels of small uremic solutes other than urea.
      Measurements made >=3 months after randomization in 1281 patients in the HEMO
      Study showed a range in the effect of high-dose treatment compared with that of
      standard treatment: from no reduction in the level of p-cresol sulfate or
      asymmetric dimethylarginine to significant reductions in the levels of
      trimethylamine oxide (-9%; 95% confidence interval [95% CI], -2% to -15%),
      indoxyl sulfate (-11%; 95% CI, -6% to -15%), and methylguanidine (-22%; 95% CI, 
      18% to -27%). Levels of three other small solutes also decreased slightly; the
      level of urea decreased 9%. All-cause mortality did not significantly relate to
      the level of any of the solutes measured. Modeling indicated that the
      intermittency of treatment along with the presence of nondialytic clearance
      and/or increased solute production accounted for the limited reduction in solute
      levels with the higher Kt/Vurea In conclusion, failure to achieve greater
      reductions in solute levels may explain the failure of high Kt/Vurea treatment to
      improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes
      varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted
      for very little of this variation. These results further suggest that an index
      only on the basis of urea does not provide a sufficient measure of dialysis
      adequacy.

PMID- 27026366
TI  - TWEAK-Fn14 Signaling Activates Myofibroblasts to Drive Progression of Fibrotic
      Kidney Disease.
AB  - The identification of the cellular origins of myofibroblasts has led to the
      discovery of novel pathways that potentially drive myofibroblast perpetuation in
      disease. Here, we further investigated the role of innate immune signaling
      pathways in this process. In mice, renal injury-induced activation of pericytes,
      which are myofibroblast precursors attached to endothelial cells, led to
      upregulated expression of TNF receptor superfamily member 12a, also known as
      fibroblast growth factor-inducible 14 (Fn14), by these cells. In live rat kidney
      slices, administration of the Fn14 ligand, TNF-related weak inducer of apoptosis
      (TWEAK), promoted pericyte-dependent vasoconstriction followed by pericyte
      detachment from capillaries. In vitro, administration of TWEAK activated and
      differentiated pericytes into cytokine-producing myofibroblasts, and further
      activated established myofibroblasts in a manner requiring canonical and
      noncanonical NF-kappaB signaling pathways. Deficiency of Fn14 protected mouse
      kidneys from fibrogenesis, inflammation, and associated vascular instability
      after in vivo injury, and was associated with loss of NF-kappaB signaling. In a
      genetic model of spontaneous CKD, therapeutic delivery of anti-TWEAK blocking
      antibodies attenuated disease progression, preserved organ function, and
      increased survival. These results identify the TWEAK-Fn14 signaling pathway as an
      important factor in myofibroblast perpetuation, fibrogenesis, and chronic disease
      progression.

PMID- 27026368
TI  - A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic
      Interstitial Nephritis.
AB  - Karyomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy
      characterized by tubulointerstitial nephritis and formation of enlarged nuclei in
      the kidneys and other tissues. We recently reported that recessive mutations in
      the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans.
      FAN1 is a major component of the Fanconi anemia-related pathway of DNA damage
      response (DDR) signaling. To study the pathogenesis of KIN, we generated a Fan1
      knockout mouse model, with abrogation of Fan1 expression confirmed by
      quantitative RT-PCR. Challenging Fan1-/- and wild-type mice with 20 mg/kg
      cisplatin caused AKI in both genotypes. In contrast, chronic injection of
      cisplatin at 2 mg/kg induced KIN that led to renal failure within 5 weeks in Fan1
      /- mice but not in wild-type mice. Cell culture studies showed decreased survival
      and reduced colony formation of Fan1-/- mouse embryonic fibroblasts and bone
      marrow mesenchymal stem cells compared with wild-type counterparts in response to
      treatment with genotoxic agents, suggesting that FAN1 mutations cause
      chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in
      the physiologic response of kidney tubular cells to DNA damage, which contributes
      to the pathogenesis of CKD. Moreover, Fan1-/- mice provide a new model with which
      to study the pathomechanisms of CKD.

PMID- 27026367
TI  - Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disruption of the
      Glomerular Glycocalyx.
AB  - Diabetic nephropathy (DN) is the leading cause of CKD in the Western world.
      Endothelin receptor antagonists have emerged as a novel treatment for DN, but the
      mechanisms underlying the protective effect remain unknown. We previously showed
      that both heparanase and endothelin-1 are essential for the development of DN.
      Here, we further investigated the role of these proteins in DN, and demonstrated
      that endothelin-1 activates podocytes to release heparanase. Furthermore,
      conditioned podocyte culture medium increased glomerular transendothelial albumin
      passage in a heparanase-dependent manner. In mice, podocyte-specific knockout of
      the endothelin receptor prevented the diabetes-induced increase in glomerular
      heparanase expression, consequent reduction in heparan sulfate expression and
      endothelial glycocalyx thickness, and development of proteinuria observed in wild
      type counterparts. Our data suggest that in diabetes, endothelin-1 signaling, as
      occurs in endothelial activation, induces heparanase expression in the podocyte,
      damage to the glycocalyx, proteinuria, and renal failure. Thus, prevention of
      these effects may constitute the mechanism of action of endothelin receptor
      blockers in DN.

PMID- 27026369
TI  - ESRD Payment Reform: First Do No Harm.

PMID- 27026371
TI  - One-pot synthesis of mesoporous silica hollow spheres with Mn-N-C integrated into
      the framework for ethylbenzene oxidation.
AB  - Mesoporous silica spheres with Mn-N-C materials integrated into the framework are
      synthesized via the surfactant (CTAB) template-assisted one-pot approach. A
      manganese porphyrin is used as the precursor of the Mn-N-C structure. The as
      prepared catalyst exhibits remarkable activity and stability in heterogeneous
      catalytic systems for ethylbenzene oxidation. 

PMID- 27026370
TI  - APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney
      Disease.
AB  - APOL1 risk variants are associated with kidney disease in blacks, but the
      mechanisms of renal injury associated with APOL1 risk variants are unknown.
      Because APOL1 is unique to humans and some primates, we created transgenic (Tg)
      mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference
      sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a
      spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not
      undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with
      highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney
      pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days
      of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT
      and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a
      pregnancy-associated phenotype that encompassed eclampsia, preeclampsia,
      fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and
      more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice
      expressed APOL1. Overall, these results suggest podocyte depletion could
      predispose individuals with APOL1 risk genotypes to kidney disease in response to
      a second stressor, and add to other published evidence associating APOL1
      expression with preeclampsia.

PMID- 27026372
TI  - A Visualization Tool to Analyse Usage of Web-Based Interventions: The Example of
      Positive Online Weight Reduction (POWeR).
AB  - BACKGROUND: Attrition is a significant problem in Web-based interventions.
      Consequently, this research aims to identify the relation between Web usage and
      benefit from such interventions. A visualization tool has been developed that
      enables researchers to more easily examine large datasets on intervention usage
      that can be difficult to make sense of using traditional descriptive or
      statistical techniques alone. OBJECTIVE: This paper demonstrates how the
      visualization tool was used to explore patterns in participants' use of a Web
      based weight management intervention, termed "positive online weight reduction
      (POWeR)." We also demonstrate how the visualization tool can be used to perform
      subsequent statistical analyses of the association between usage patterns,
      participant characteristics, and intervention outcome. METHODS: The visualization
      tool was used to analyze data from 132 participants who had accessed at least one
      session of the POWeR intervention. RESULTS: There was a drop in usage of optional
      sessions after participants had accessed the initial, core POWeR sessions, but
      many users nevertheless continued to complete goal and weight reviews. The POWeR
      tools relating to the food diary and steps diary were reused most often.
      Differences in participant characteristics and usage of other intervention
      components were identified between participants who did and did not choose to
      access optional POWeR sessions (in addition to the initial core sessions) or
      reuse the food and steps diaries. Reuse of the steps diary and the getting
      support tools was associated with greater weight loss. CONCLUSIONS: The
      visualization tool provided a quick and efficient method for exploring patterns
      of Web usage, which enabled further analyses of whether different usage patterns
      were associated with participant characteristics or differences in intervention
      outcome. Further usage of visualization techniques is recommended to (1) make
      sense of large datasets more quickly and efficiently; (2) determine the likely
      active ingredients in Web-based interventions, and thereby enhance the benefit
      they may provide; and (3) guide in designing (or redesigning) of future
      interventions to promote greater use and engagement by enabling users to easily
      access valued intervention content/tools. TRIAL REGISTRATION: International
      Standard Randomized Controlled Trial Number (ISRCTN): 31685626;
      http://www.isrctn.com/ISRCTN31685626 (Archived by WebCite at
      http://www.webcitation.org/6YXYIw9vc).

PMID- 27026373
TI  - Effects of taurine on gut microbiota and metabolism in mice.
AB  - As being a necessary amino acid, taurine plays an important role in the
      regulation of neuroendocrine functions and nutrition. In this study, effects of
      taurine on mice gut microbes and metabolism were investigated. BALB/C mice were
      randomly divided into three experimental groups: The first group was administered
      saline (CK), the second was administered 165 mg/kg natural taurine (NE) and the
      third one administered 165 mg/kg synthetic taurine (CS). Gut microbiota
      composition in mice feces was analyzed by metagenomics technology, and the
      content of short-chain fatty acids (SCFA) in mice feces was detected by gas
      chromatography (GC), while the concentrations of lipopolysaccharide (LPS) and
      superoxide dismutase (SOD) were detected by a LPS ELISA kit and a SOD assay kit,
      respectively. The results showed that the effect of taurine on gut microbiota
      could reduce the abundance of Proteobacteria, especially Helicobacter. Moreover,
      we found that the SCFA content was increased in feces of the NE group while LPS
      content was decreased in serum of the NE group; the SOD activity in serum and
      livers of the NE and CS groups were not changed significantly compare to that of
      the CK group. In conclusion, taurine could regulate the gut micro-ecology, which
      might be of benefit to health by inhibiting the growth of harmful bacteria,
      accelerating the production of SCFA and reducing LPS concentration.

PMID- 27026374
TI  - Effect of ejection fraction on left ventricular remodeling in aortic
      insufficiency.
AB  - BACKGROUND: Due to ventricular compensatory mechanisms, patients with severe
      aortic regurgitation are generally asymptomatic. Severe left ventricular
      dysfunction develops annually in 20% of non-operated cases, and the prognosis in
      those cases is poor. Although surgery is recommend in patients with left
      ventricular dysfunction, surgeons are wary. We investigated the changes in
      ventricular and effort capacity after surgery in patients with normal and
      abnormal left ventricular function. METHODS: We retrospectively examined the data
      of patients with aortic regurgitation who underwent aortic valve replacement in
      our clinic between 1993 and 2013. Those who had previous cardiac surgery,
      chemotherapy, radiotherapy, renal dysfunction, diabetes mellitus, or preoperative
      arrhythmias were excluded. The 113 patients were divided into 2 groups according
      to ejection fraction. RESULTS: In patients with ejection fraction <50%,
      interventricular septal thickness, posterior wall thickness, and left ventricular
      mass were significantly greater than in the ejection fraction >=50% group (p <
      0.01). No significant differences in intensive care unit stay and hospitalization
      were determined. No mortality was observed. Ejection fraction and effort capacity
      increased significantly after aortic valve replacement in both groups, and
      interventricular septal thickness, posterior wall thickness, and left ventricular
      mass decreased in both groups. CONCLUSIONS: Significant left ventricular
      functional improvements can be achieved after aortic valve replacement in
      patients with severe aortic regurgitation who develop left ventricular
      dysfunction. Despite the reported higher surgical mortality in this patient
      group, surgical treatment offers a survival benefit. We recommend surgical
      treatment in patients with severe aortic regurgitation who develop left
      ventricular dysfunction.

PMID- 27026376
TI  - CCR5 interaction with HIV-1 Env contributes to Env-induced depletion of CD4 T
      cells in vitro and in vivo.
AB  - BACKGROUND: CD4 T cell depletion during HIV-1 infection is associated with AIDS
      disease progression, and the HIV-1 Env protein plays an important role in the
      process. Together with CXCR4, CCR5 is one of the two co-receptors that interact
      with Env during virus entry, but the role of CCR5 in Env-induced pathogenesis is
      not clearly defined. We have investigated CD4 T cell depletion mechanisms caused
      by the Env of a highly pathogenic CXCR4/CCR5 dual-tropic HIV-1 isolate R3A.
      RESULTS: We report here that R3A infection induced depletion of both infected and
      uninfected "bystander" CD4 T cells, and treatment with CCR5 antagonist TAK-779
      inhibited R3A-induced bystander CD4 T cell depletion without affecting virus
      replication. To further define the role of Env-CCR5 interaction, we utilized an
      Env-mutant of R3A, termed R3A-5/6AA, which has lost CCR5 binding capability.
      Importantly, R3A-5/6AA replicated to the same level as wild type R3A by using
      CXCR4 for viral infection. We found the loss of CCR5 interaction resulted in a
      significant reduction of bystander CD4 T cells death during R3A-5/6AA infection,
      whereas stimulation of CCR5 with MIP1-beta increased bystander pathogenesis
      induced by R3A-5/6AA. We confirmed our findings using a humanized mouse model,
      where we observed similarly reduced pathogenicity of the mutant R3A-5/6AA in
      various lymphoid organs in vivo. CONCLUSION: We provide the first evidence that
      shows CCR5 interaction with a dual-tropic HIV-1 Env played a significant role in
      Env-induced depletion of CD4 T cells.

PMID- 27026375
TI  - Prevention of hepatitis B virus-associated liver diseases by antiviral therapy.
AB  - Hepatitis B virus (HBV) is a major cause of acute and chronic hepatitis,
      cirrhosis and hepatocellular carcinoma, particularly in Asia-Pacific countries.
      The major complications in HBV carriers are hepatocellular carcinoma (HCC), liver
      failure and esophageal varices following the progression to cirrhosis, while some
      develop HCC without cirrhosis. The progression to liver fibrosis and these other
      complications could be prevented by treatment with nucleos(t)ide analogues
      (NUCs); however, NUCs must be continuously administered for a long time.
      Peginterferon could lead to HBV surface antigen loss. It is difficult to use
      peginterferon in HBV-infected patients with decompensated cirrhosis. Acute liver
      failure due to HBV infection and acute exacerbation of chronic hepatitis B could
      be treated by NUCs. Universal vaccination programs against HBV could prevent new
      HBV infections globally. Here, we review the currently available treatments for
      HBV infection. 

PMID- 27026377
TI  - Skin conductance in neonates suffering from abstinence syndrome and unexposed
      newborns.
AB  - The aims of this study were to compare the skin conductance (SC) of newborns with
      opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns
      and to evaluate the potential of SC readings to detect distress in the context of
      NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was
      measured at nine specific times during their first 6 weeks of life. The number of
      SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the
      mean level of SC were recorded and analyzed. The SC of newborns treated for
      symptoms of NAS differed significantly from the SC of unexposed newborns with
      regard to the NSCF/s (p = 0.04). With the mean level of SC, we observed an
      interaction between groups over time (p value for interaction = 0.02). With
      increasing postnatal age, we observed higher values in all three SC parameters.
      CONCLUSION: The NSCF/s and the mean level of SC appear to be suitable to reflect
      the distress of newborns suffering from NAS. As it is known that the sensitivity
      of SC increases with the level of stress experienced, its potential to indicate
      elevated stress levels in infants with NAS should be investigated in future
      studies evaluating different therapy regimens. WHAT IS KNOWN: * Skin conductance
      is a result of the filling of palmar and plantar sweat glands innervated by the
      sympathetic nervous system * Skin conductance can be used as a measure of stress
      and pain in newborns What is New: * Skin conductance of newborns with neonatal
      abstinence syndrome (NAS) differs significantly from the SC of non-substance
      exposed newborns during the first 6 weeks of life * Skin conductance appears to
      reflect the increased distress of infants with NAS.

PMID- 27026379
TI  - Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic
      Events Registry.
AB  - Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and
      predictors are still elusive. To investigate this issue, the Italian Society of
      Internal Medicine undertook the "Portal vein thrombosis Relevance On Liver
      cirrhosis: Italian Venous thrombotic Events Registry" (PRO-LIVER). This
      prospective multicenter study includes consecutive cirrhotic patients undergoing
      Doppler ultrasound examination of the portal area to evaluate the prevalence and
      incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven
      hundred and fifty-three (68 % men; 64 +/- 12 years) patients were included in the
      present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral
      (44 %) etiology was predominant. Around half of the patients had a mild-severity
      disease according to the Child-Pugh score; hepatocellular carcinoma was present
      in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % (n
      = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the
      portal vein thrombosis patients (n = 81) were not treated with anticoagulant
      therapy. Logistic step-forward multivariate analysis demonstrated that previous
      portal vein thrombosis (p < 0.001), Child-Pugh Class B + C (p < 0.001),
      hepatocellular carcinoma (p = 0.01), previous upper gastrointestinal bleeding (p
      = 0.030) and older age (p = 0.012) were independently associated with portal vein
      thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis,
      particularly in patients with moderate-severe liver failure. The apparent
      undertreatment of patients with portal vein thrombosis is a matter of concern and
      debate, which should be addressed by planning interventional trials especially
      with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547.

PMID- 27026380
TI  - Spaced learning using emails to integrate psychiatry into general medical
      curriculum: Keep psychiatry in mind.
AB  - OBJECTIVES: Traditionally, medical students on clinical rotations receive
      instruction on principles of mental health only during the psychiatry clerkship.
      We used emails to insert teaching of psychiatric concepts beyond the psychiatry
      clerkship into other rotations using the method of spaced learning, the delivery
      of brief morsels of information repeated over time intervals. We predicted that
      the intervention would improve attitudes and confidence towards the integration
      of psychiatry and knowledge retention. METHODS: We developed and distributed a
      series of emails relating key psychiatric concepts targeted to the other core
      clerkships. RESULTS: In a cluster-randomized trial over one academic year
      (intervention group n = 71, control group n = 61), scores on the Attitudes and
      Confidence in the Integration of Psychiatry scale and on the knowledge quiz did
      not differ significantly. Students who actively engaged with the emails
      demonstrated significantly higher scores on the knowledge test. Email users
      valued the timing, format of delivery and application of psychiatric principles
      outside the psychiatric setting. Participants recommended simplifying the format
      and previewing the benefits of spaced learning to increase utilization.
      CONCLUSION: Delivering spaced learning through emails, within a curriculum
      designed to foster engagement, may provide an efficient means of addressing the
      widely-recognized but elusive goal of integrating teaching across medical
      disciplines.

PMID- 27026378
TI  - Systematic review: antihypertensive drug therapy in patients of African and South
      Asian ethnicity.
AB  - Despite the large differences in the epidemiology of hypertension across Europe,
      treatment strategies are similar for national populations of white European
      descent. However, hypertensive patients of African or South Asian ethnicity may
      require ethnic-specific approaches, as these population subgroups tend to have
      higher blood pressure at an earlier age that is more difficult to control, a
      higher occurrence of diabetes, and more target organ damage with earlier
      cardiovascular mortality. Therefore, we systematically reviewed the evidence on
      antihypertensive drug treatment in South Asian and African ethnicity patients. We
      used the Cochrane systematic review methodology to retrieve trials in electronic
      databases including CENTRAL, PubMed, and Embase from their inception through
      November 2015; and with handsearch. We retrieved 4596 reports that yielded 35
      trials with 7 classes of antihypertensive drugs in 25,540 African ethnicity
      patients. Aside from the well-known blood pressure efficacy of calcium channel
      blockers and diuretics, with lesser effect of ACE inhibitors and beta-blockers,
      nebivolol was not more effective than placebo in reducing systolic blood pressure
      levels. Trials with morbidity and mortality outcomes indicated that lisinopril
      and losartan-based therapy were associated with a greater incidence of stroke and
      sudden death. Furthermore, 1581 reports yielded 16 randomized controlled trials
      with blood pressure outcomes in 1719 South Asian hypertensive patients. In
      contrast with the studies in African ethnicity patients, there were no
      significant differences in blood pressure lowering efficacy between drugs, and no
      trials available with mortality outcomes. In conclusion, in patients of African
      ethnicity, treatment initiated with ACE inhibitor or angiotensin II receptor
      blocker monotherapy was associated with adverse cardiovascular outcomes. We found
      no evidence of different efficacy of antihypertensive drugs in South Asians, but
      there is a need for trials with morbidity and mortality outcomes. Screening for
      cardiovascular risk at a younger age, treating hypertension at lower thresholds,
      and new delivery models to find, treat and follow hypertensives in the community
      may help reduce the excess cardiovascular mortality in these high-risk groups. 

PMID- 27026381
TI  - VIP: an integrated pipeline for metagenomics of virus identification and
      discovery.
AB  - Identification and discovery of viruses using next-generation sequencing
      technology is a fast-developing area with potential wide application in clinical
      diagnostics, public health monitoring and novel virus discovery. However,
      tremendous sequence data from NGS study has posed great challenge both in
      accuracy and velocity for application of NGS study. Here we describe VIP ("Virus
      Identification Pipeline"), a one-touch computational pipeline for virus
      identification and discovery from metagenomic NGS data. VIP performs the
      following steps to achieve its goal: (i) map and filter out background-related
      reads, (ii) extensive classification of reads on the basis of nucleotide and
      remote amino acid homology, (iii) multiple k-mer based de novo assembly and
      phylogenetic analysis to provide evolutionary insight. We validated the
      feasibility and veracity of this pipeline with sequencing results of various
      types of clinical samples and public datasets. VIP has also contributed to timely
      virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in
      the performance of unbiased NGS-based clinical studies with demand of short
      turnaround time. VIP is released under GPLv3 and is available for free download
      at: https://github.com/keylabivdc/VIP.

PMID- 27026383
TI  - Validation Study of the World Health Organization and Pan American Health
      Organization Hospital-Based Disaster Preparedness Questionnaires in Nepal.

PMID- 27026382
TI  - Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in
      Xp11.2 translocation renal cell carcinoma.
AB  - Two main signaling pathways, PI3K-AKT-mTOR and RAS-MAPK, are involved in
      transmitting the proliferative signals which play critical roles in human
      cancers. However, the functions of these pathways in Xp11.2 RCC remain undefined.
      This study aimed to explore the expression of mTOR and MAPK cascades in Xp11.2
      RCC and to assess the prognostic significance of proteins evaluated.
      Immunohistochemistry was performed to evaluate the expression of 4EBP1, p-4EBP1,
      p-mTOR, p-S6K and p-MAPK in 36 adult Xp11.2 RCC patients who were confirmed by
      FISH assay. Cox regression models were used to evaluate the prognostic value of
      all covariates. Among 36 assessed patients, 14 (38.9%), 26 (72.2%), 16 (44.4%),
      19 (52.8%), and 9 (25.0%) patients showed high expression of 4EBP1, p-4EBP1, p
      mTOR, p-S6K, and p-MAPK, respectively. We noted that p-4EBP1 expression was
      significantly correlated with lymph node metastases (P = 0.027). Multivariate
      analysis showed that high p-4EBP1 expression was an independent adverse
      prognostic factor for both PFS (HR = 33.750, P = 0.017) and OS (HR = 56.111, P =
      0.026). Our findings suggest that p-4EBP1 may serve as a funnel factor that
      converge the upstream proliferative oncogenic signals. Effective inhibition of
      the pathways responsible for 4E-BP1 phosphorylation might be a useful strategy to
      improve the outcome of Xp11.2 RCC patients.

PMID- 27026384
TI  - Psychometric Properties of the Kidney Disease Quality of Life-36 Questionnaire
      (KDQOL-36TM).
AB  - The Kidney Disease Quality of Life-36 Questionnaire (KDQOL-36TM), modified by
      RAND, has been widely used for measurement of quality of life among hemodialysis
      or peritoneal dialysis patients. The purpose of this study was to refine and
      evaluate, by using confirmatory factor analysis, the structure of the KDQOL-36TM
      when the questionnaire was used to evaluate chronic kidney disease patients in
      Stages 1 to 5 in Taiwan. The psychometric properties of the translated version
      were determined among Mandarin-speaking adults (N = 428). Because the sample data
      did not fit the hypothetical model, one item was deleted and nine error terms
      were estimated. After improving the model fit, the modified model was presented
      as follows: chi(2) = 1390.903, chi(2)/df = 2.711, p < .001, goodness-of-fit index
      = .833, adjusted goodness-of-fit index = .806, root mean square error of
      approximation = .063. According to the study results, the researchers suggest
      that because of content overlap, some items may be deducted from the KDQOL-36TM.

PMID- 27026385
TI  - Color image encryption scheme using CML and DNA sequence operations.
AB  - In this paper, an encryption algorithm for color images using chaotic system and
      DNA (Deoxyribonucleic acid) sequence operations is proposed. Three components for
      the color plain image is employed to construct a matrix, then perform confusion
      operation on the pixels matrix generated by the spatiotemporal chaos system,
      i.e., CML (coupled map lattice). DNA encoding rules, and decoding rules are
      introduced in the permutation phase. The extended Hamming distance is proposed to
      generate new initial values for CML iteration combining color plain image.
      Permute the rows and columns of the DNA matrix and then get the color cipher
      image from this matrix. Theoretical analysis and experimental results prove the
      cryptosystem secure and practical, and it is suitable for encrypting color images
      of any size. 

PMID- 27026386
TI  - [Dyslipidemia and atherogenic risk in patients with rheumatoid arthritis].
AB  - INTRODUCTION: Dyslipidaemia is one of the main risk factors for atherosclerotic
      cardiovascular disease. Patients with rheumatoid arthritis have 2-3 times more
      cardiovascular risk, which is partly due to the pattern of lipids which increase
      the atherogenic index. METHODS: A descriptive, cross-sectional, observational and
      prospective study was conducted on 82 patients, selected for their lipid profile.
      Variables associated with the disease and the drugs used were recorded.
      Atherogenic risk was calculated, with Chi square being used for categorical
      variables, and the Mann-Whitney test for the continuous ones. RESULTS: The
      dyslipidaemia frequency was 54.9%. The most frequent age range of dyslipidaemia
      was between 51 and 60 years. Patients with type i obesity had a higher frequency
      of dyslipidaemia. Less dyslipidaemia was found with a lower rate of disease
      activity. Patients with cyclic citrullinated anti-peptide antibodies and positive
      rheumatoid factor, erythrocyte sedimentation rate>13mm or CRP>2mg/L had a higher
      frequency of dyslipidaemia. The mean Castelli atherogenic index was 4.36, the
      index of Kannel was 2.59, and triglycerides/HDL-c ratio was 3.83.Patients with
      dyslipidaemia showed a higher frequency of positive rheumatoid factor (P=.0008),
      and those patients who were taking hydroxychloroquine had a lower frequency of
      dyslipidaemia P=.03. CONCLUSIONS: Patients with rheumatoid arthritis have a pro
      atherogenic lipid profile. It is important to know this and treat it to reduce
      cardiovascular risk.

PMID- 27026387
TI  - Genetic variant in IL-33 is associated with idiopathic recurrent miscarriage in
      Chinese Han population.
AB  - Recurrent miscarriage (RM) is the occurrence of repeated pregnancies that end in
      miscarriage of the fetus before 20 weeks of gestation. At least 50% of the RM
      patients are considered idiopathic. High IL-33 levels are critical in early
      pregnancy and impact the outcome of subsequent pregnancies. However, the
      association of polymorphisms of IL-33 with idiopathic RM is still unclear. The
      present study was initiated to investigate whether IL-33 polymorphisms are risk
      factors for idiopathic RM in Chinese Han population. Study subjects comprised of
      321 cases and 384 controls. Five polymorphisms (rs10435816, rs16924159,
      rs16924171, rs1929992, rs1332290) in IL-33 and serum IL-33 concentrations were
      assessed. rs16924159 variant exhibits significant association with RM in additive
      and recessive genetic model (additive model P = 0.015, recessive model P =
      0.007). In contrast, rs10435816, rs16924171, rs1929992 and rs1332290 are not
      significantly associated with RM. Serum IL-33 levels are significantly lower in
      RM cases than in control (173.51 +/- 94.12 versus. 200.97 +/- 110.06 (pg/ml), P =
      4.57 * 10(-4)). There are lower levels of serum IL-33 in rs16924159 homozygous
      mutant (AA) than homozygous wild-type (GG) in this study population, including
      cases and control groups (172.18 +/- 103.01 versus. 205.82 +/- 119.01 (pg/ml), P
      = 0.006). Reduced IL-33 levels and rs16924159 IL-33 variant may contribute to the
      pathogenesis of idiopathic RM in Chinese Han population.

PMID- 27026389
TI  - Asking 'What about' questions in chronic illness self-management meetings.
AB  - OBJECTIVES: This study investigates 'What about' questions asked by patients in
      the course of diabetes self-management groups led by nurses, and explores their
      functions in these empowerment-informed settings. METHODS: Conversation Analysis
      of 24 video-recorded sessions of a Start Insulin Group Programme for patients
      with type 2 diabetes, in a diabetes centre in the South of England. The groups
      included 2-7 patients and were led by 5 nurses, all of whom had received training
      in the empowerment approach. RESULTS: The analysis revealed a prevalence of
      single-unit 'Whatabout X' questions and found that they were used to embed
      requests for information in current or just closed activities. The nurses always
      provided the information, but could ask patients to specify the content of the
      question and collaborate to the answer. CONCLUSION: The analysis suggests that
      the short form of the question may be adapting to the nurses' restraint in giving
      recommendations or immediate responses to information seeking-questions. PRACTICE
      IMPLICATIONS: When healthcare communication practices are shaped in observance to
      a theoretical approach, such as empowerment, it is recommendable that
      practitioners monitor not only what they do, but also how patients change their
      habitual forms of speech in response.

PMID- 27026388
TI  - The diabetes nutrition education study randomized controlled trial: A comparative
      effectiveness study of approaches to nutrition in diabetes self-management
      education.
AB  - OBJECTIVE: To compare the effectiveness of different approaches to nutrition
      education in diabetes self-management education and support (DSME/S). METHODS: We
      randomized 150 adults with type 2 diabetes to either certified diabetes educator
      (CDE)-delivered DSME/S with carbohydrate gram counting or the modified plate
      method versus general health education. The primary outcome was change in HbA1C
      over 6 months. RESULTS: At 6 months, HbA1C improved within the plate method [
      0.83% (-1.29, -0.33), P<0.001] and carbohydrate counting [-0.63% (-1.03, -0.18),
      P=0.04] groups but not the control group [P=0.34]. Change in HbA1C from baseline
      between the control and intervention groups was not significant at 6 months
      (carbohydrate counting, P=0.36; modified plate method, P=0.08). In a pre
      specified subgroup analysis of patients with a baseline HbA1C 7-10%, change in
      HbA1C from baseline improved in the carbohydrate counting [-0.86% (-1.47, -0.26),
      P=0.006] and plate method groups [-0.76% (-1.33, -0.19), P=0.01] compared to
      controls. CONCLUSION: CDE-delivered DSME/S focused on carbohydrate counting or
      the modified plate method improved glycemic control in patients with an initial
      HbA1C between 7 and 10%. PRACTICE IMPLICATIONS: Both carbohydrate counting and
      the modified plate method improve glycemic control as part of DSME/S.

PMID- 27026390
TI  - Ultrasound Guided Compression Versus Ultrasound Guided Thrombin Injection for the
      Treatment of Post-Catheterization Femoral Pseudoaneurysms: Systematic Review and
      Meta-Analysis of Comparative Studies.
AB  - OBJECTIVE: To compare results of ultrasound based techniques (ultrasound guided
      compression-(UGC) versus ultrasound guided thrombin injection (UGTI)) to treat
      iatrogenic post-catheterization femoral pseudoaneurysms. METHODS: The study
      design involved a systematic review of the literature and meta-analysis of
      comparative studies. The MEDLINE, CENTRAL, and OpenGray databases were searched
      up to October 2015. Primary outcome measure was efficacy, while other outcomes
      examined were safety (complication rate), duration of the procedure, length of
      hospitalization, and cost of methods. The random effects model was used to
      calculate combined overall effect sizes of pooled data. Data are presented as the
      odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI).
      RESULTS: Two randomized control trials and 11 observational studies were included
      in the analysis. Overall, 786 and 318 subjects underwent UGC and UGTI
      respectively. The latter modality resulted in a significantly higher success rate
      (97.4% vs. 69.3%, OR 0.06, 95% CI 0.03-0.11) while the complication rate for both
      techniques was very low (0.69% vs. 0.78%, OR 1.77, 95% CI 0.40-7.88). Data
      regarding procedural duration and length of hospitalization were very scarce,
      favoring UGTI (procedural time: MD 35.53 min, 9.11-63.95, length of
      hospitalization MD 1.99 days, -0.31-4.29). Scarcity of data did not allow proper
      cost analysis, but two studies suggested that UGTI may offer reduced treatment
      costs. CONCLUSION: Available evidence suggests that UGTI is superior in terms of
      efficacy and as safe as UGC and thus should be used as the primary modality for
      the treatment of post-catheterization femoral pseudoaneurysms.

PMID- 27026391
TI  - Systematic Review and Meta-Analysis of Utility of Graduated Compression Stockings
      in Prevention of Post-Thrombotic Syndrome.
AB  - BACKGROUND: Up to 50% of patients develop post-thrombotic syndrome (PTS)
      following their first proximal deep vein thrombosis (DVT). This meta-analysis
      aims to evaluate the effectiveness of graduated compression stockings (GCS) in
      preventing PTS. METHOD: Medline, Embase, Cochrane Database of Systematic Reviews,
      and ClinicalTrials.gov were electronically searched from inception to January
      2015 for studies investigating the effect of GCS in preventing PTS. All
      randomised control trials were considered for inclusion if they compared the
      efficacy of GCS (30-40 mmHg at the ankle) with either placebo or no stockings in
      adults with new proximal lower limb DVT. Methodological assessment, using the
      Cochrane Risk of Bias Tool, and data extraction was performed by two independent
      reviewers. The effect of GCS was expressed as the risk difference (RD). RESULTS:
      A total of 686 articles were screened. Three randomised controlled trials
      inclusive of 1,177 patients were eligible for inclusion. PTS developed in 49-70%
      of control patients at 5 years. High statistical heterogeneity was observed
      between trials (all PTS: I(2) = 0.94; severe PTS: I(2) = 0.79). The risk
      difference in PTS incidence between control and GCS arms varied from 0% to 39%
      between trials. In trials with a higher baseline prevalence of PTS, a visual
      trend towards more benefit with GCS was noted. CONCLUSION: Uncertainty because of
      sampling variability and heterogeneity was too high to conclude in favour or
      against an effect of wearing compression stockings in preventing PTS. An effect
      may be present for higher values of baseline risk. Further evidence is needed.
      Article history.

PMID- 27026393
TI  - Course of acute pancreatitis in diabetic patients.
AB  - INTRODUCTION: In recent years, in many European countries, morbidity due to acute
      pancreatitis (AP) has shown a growing tendency. Some studies indicate an
      increased risk of contracting AP in the AIM: The objective of the presented study
      was evaluation of the clinical course of AP in patients with diabetes. METHODS:
      The study covered all patients with the diagnosis of AP, treated in surgical
      wards. Into the group of diabetic patients were qualified those who during
      medical history taking confirmed the diagnosis of type 1 or type 2 diabetes prior
      to hospitalization due to AP. RESULTS: Into the study were enrolled 963 patients
      hospitalized due to AP. In this group there were 87 (9%) patients with diabetes.
      In patients with diabetes, gallstones were the cause of the disease significantly
      more often (46% vs. 32%). In the majority of cases, the course of AP was mild;
      however, in 10.3% of patients with diabetes, the course of the disease was
      moderately severe, and in 12.7% - severe AP was observed. No differences were
      found in mortality due to AP between the groups. Systemic failure was more
      frequently observed in the group of patients with D.T.2. 5.4% and as many as
      23.1% with D.T.1. vs. 5.1% of those without diabetes, the differences were
      statistically insignificant. CONCLUSIONS: The frequency of occurrence of AP in
      patients with diabetes increases with age, and is most often related with
      gallstones. The clinical course of AP in this group of patients is more often
      severe, with systemic failure in patients with type 1 diabetes. KEY WORDS: Acute
      pancreatitis, Diabetes, Etiology.

PMID- 27026394
TI  - Evaluating the Usability and Perceived Impact of an Electronic Medical Record
      Toolkit for Atrial Fibrillation Management in Primary Care: A Mixed-Methods Study
      Incorporating Human Factors Design.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common and preventable cause of stroke.
      Barriers to reducing stroke risk through appropriate prescribing have been
      identified at the system, provider, and patient levels. To ensure a multifaceted
      initiative to address these barriers is effective, it is essential to incorporate
      user-centered design to ensure all intervention components are optimized for
      users. OBJECTIVE: To test the usability of an electronic medical record (EMR)
      toolkit for AF in primary care with the goal of further refining the intervention
      to meet the needs of primary care clinicians. METHODS: An EMR-based toolkit for
      AF was created and optimized through usability testing and iterative redesign
      incorporating a human factors approach. A mixed-methods pilot study consisting of
      observations, semi-structured interviews, and surveys was conducted to examine
      usability and perceived impact on patient care and workflow. RESULTS: A total of
      14 clinicians (13 family physicians and 1 nurse practitioner) participated in the
      study. Nine iterations of the toolkit were created in response to feedback from
      clinicians and the research team; interface-related changes were made, additional
      AF-related resources were added, and functionality issues were fixed to make the
      toolkit more effective. After improvements were made, clinicians expressed that
      the toolkit improved accessibility to AF-related information and resources,
      served as a reminder for guideline-concordant AF management, and was easy to use.
      Most clinicians intended to continue using the toolkit for patient care. With
      respect to impact on care, clinicians believed the toolkit increased the
      thoroughness of their assessments for patients with AF and improved the quality
      of AF-related care received by their patients. CONCLUSIONS: The positive feedback
      surrounding the EMR toolkit for AF and its perceived impact on patient care can
      be attributed to the adoption of a user-centered design that merged clinically
      important information about AF management with user needs. This study
      demonstrates the utility of a human factors approach to piloting and refining an
      intervention prior to wide-scale implementation.

PMID- 27026396
TI  - New insights into the structure, assembly and biological roles of 10-12 nm
      connective tissue microfibrils from fibrillin-1 studies.
AB  - The 10-12 nm diameter microfibrils of the extracellular matrix (ECM) impart both
      structural and regulatory properties to load-bearing connective tissues. The main
      protein component is the calcium-dependent glycoprotein fibrillin, which
      assembles into microfibrils at the cell surface in a highly regulated process
      involving specific proteolysis, multimerization and glycosaminoglycan
      interactions. In higher metazoans, microfibrils act as a framework for elastin
      deposition and modification, resulting in the formation of elastic fibres, but
      they can also occur in elastin-free tissues where they perform structural roles.
      Fibrillin microfibrils are further engaged in a number of cell matrix
      interactions such as with integrins, bone morphogenetic proteins (BMPs) and the
      large latent complex of transforming growth factor-beta (TGFbeta). Fibrillin-1
      (FBN1) mutations are associated with a range of heritable connective disorders,
      including Marfan syndrome (MFS) and the acromelic dysplasias, suggesting that the
      roles of 10-12 nm diameter microfibrils are pleiotropic. In recent years the use
      of molecular, cellular and whole-organism studies has revealed that the
      microfibril is not just a structural component of the ECM, but through its
      network of cell and matrix interactions it can exert profound regulatory effects
      on cell function. In this review we assess what is known about the molecular
      properties of fibrillin that enable it to assemble into the 10-12 nm diameter
      microfibril and perform such diverse roles.

PMID- 27026397
TI  - Contributions of a unique beta-clamp to substrate recognition illuminates the
      molecular basis of exolysis in ferulic acid esterases.
AB  - Lignocellulosic biomass is a promising renewable resource; however,
      deconstruction of this material is still the rate-limiting step. Major obstacles
      in the biocatalytic turnover of lignocellulose are ester-linked decorations that
      prevent access to primary structural polysaccharides. Enzymes targeting these
      esters represent promising biotools for increasing bioconversion efficiency.
      Ruminant livestock are unique in their ability to degrade lignocellulose through
      the action of their gut microbiome. The anaerobic fungi (phylum
      Neocallimastigomycota) are key members of this ecosystem that express a large
      repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity
      with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat
      (2014) Nucleic Acids Res. 42: , D490-D495]. We have identified a carbohydrate
      esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces
      mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence
      [1.55 A (1 A=0.1 nm)] and absence (1.60 A) of ferulic acid. AmCE1 adopts an
      alpha/beta-hydrolase fold that is structurally conserved with bacterial FAEs, and
      possesses a unique loop, termed the beta-clamp, that encloses the ligand.
      Isothermal titration calorimetry reveals that substrate binding is driven by
      enthalpic contributions, which overcomes a large entropic penalty. A comparative
      analysis of AmCE1 with related enzymes has uncovered the apparent structural
      basis for differential FAE activities targeting cross-linking ferulic acid
      conjugates compared with terminal decorations. Based on comparisons to
      structurally characterized FAEs, we propose that the beta-clamp may define the
      structural basis of exolytic activities in FAEs. This provides a structure-based
      tool for predicting exolysis and endolysis in CE1. These insights hold promise
      for rationally identifying enzymes tailored for bioconversion of biomass with
      variations in cell wall composition.

PMID- 27026398
TI  - BRCA1 affects protein phosphatase 6 signalling through its interaction with
      ANKRD28.
AB  - The tumour suppressor BRCA1 (breast and ovarian cancer-susceptibility gene 1) is
      implicated in several nuclear processes including DNA repair, transcription
      regulation and chromatin remodelling. BRCA1 also has some cytoplasmic functions
      including a pro-apoptotic activity. We identified ANKRD28 (ankyrin repeat domain
      28) as a novel BRCA1-interacting protein in a yeast two-hybrid screen and
      confirmed this interaction by reciprocal immunoprecipitations of the two
      overexpressed proteins. Endogenous interaction between BRCA1 and ANKRD28 was also
      observed by co-immunoprecipitation and located in the cytoplasm by proximity
      ligation assay. The main site of interaction of ANKRD28 on BRCA1 is located in
      its intrinsically disordered scaffold central region. Whereas ANKRD28 silencing
      results in a destabilization of IkappaBepsilon (inhibitor of nuclear factor
      kappaBepsilon) through its activation of PP6 (protein phosphatase 6) co-regulator
      upon TNFalpha (tumour necrosis factor alpha) stimulation, BRCA1 overexpression
      stabilizes IkappaBepsilon. A truncated form of BRCA1 that does not interact with
      ANKRD28 has no such effect. Our findings suggest that BRCA1 is a novel modulator
      of PP6 signalling via its interaction with ANKRD28. This new cytoplasmic process
      might participate in BRCA1 tumour-suppressor function. 

PMID- 27026395
TI  - Protein oxidation and peroxidation.
AB  - Proteins are major targets for radicals and two-electron oxidants in biological
      systems due to their abundance and high rate constants for reaction. With highly
      reactive radicals damage occurs at multiple side-chain and backbone sites. Less
      reactive species show greater selectivity with regard to the residues targeted
      and their spatial location. Modification can result in increased side-chain
      hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent
      cross-linking or hydrophobic interactions, protein unfolding and altered
      conformation, altered interactions with biological partners and modified
      turnover. In the presence of O2, high yields of peroxyl radicals and peroxides
      (protein peroxidation) are formed; the latter account for up to 70% of the
      initial oxidant flux. Protein peroxides can oxidize both proteins and other
      targets. One-electron reduction results in additional radicals and chain
      reactions with alcohols and carbonyls as major products; the latter are commonly
      used markers of protein damage. Direct oxidation of cysteine (and less commonly)
      methionine residues is a major reaction; this is typically faster than with H2O2,
      and results in altered protein activity and function. Unlike H2O2, which is
      rapidly removed by protective enzymes, protein peroxides are only slowly removed,
      and catabolism is a major fate. Although turnover of modified proteins by
      proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon),
      can be efficient, protein hydroperoxides inhibit these pathways and this may
      contribute to the accumulation of modified proteins in cells. Available evidence
      supports an association between protein oxidation and multiple human pathologies,
      but whether this link is causal remains to be established. 

PMID- 27026399
TI  - Human cytomegalovirus gH stability and trafficking are regulated by ER-associated
      degradation and transmembrane architecture.
AB  - The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long
      persistence within its human host. While benign in healthy individuals, CMV poses
      a significant threat to the immune compromised, including transplant recipients
      and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of
      fibroblasts, and together with the gH/gL/UL128/130/131 a pentameric complex
      permits infection of epithelial, endothethial, and myeloid cells. Given the
      central role of the gH/gL complex during infection, we were interested in
      studying cellular trafficking of the gH/gL complex through generation of human
      cells that stably express gH and gL. When expressed alone, CMV gH and gL were
      degraded through the ER-associated degradation (ERAD) pathway. However, co
      expression of these proteins stabilized the polypeptides and enhanced their cell
      surface expression. To further define regulatory factors involved in gH/gL
      trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail
      were replaced with that of human CD4 protein permitted cell surface gH expression
      in absence of gL. We thus demonstrate the ability of distinct cellular processes
      to regulate the trafficking of viral glycoproteins. Collectively, the data
      provide insight into the processing and trafficking requirements of CMV envelope
      protein complexes and provide an example of the co-opting of cellular processes
      by CMV. 

PMID- 27026400
TI  - Diabetes and cardiovascular disease: pathophysiology of a life-threatening
      epidemic.
AB  - Diabetes is associated with the development of premature cardiovascular disease
      (CVD), which relates to the clustering of risk factors such as dyslipidaemia,
      hypertension, obesity and hyperglycaemia in the presence of insulin resistance.
      In addition, diabetes is associated with an inflammatory and pro-thrombotic
      environment, exacerbating the development of atherothrombosis. Insulin resistance
      and hyperglycaemia both contribute to the development of endothelial cell
      dysfunction and increased oxidative stress, culminating in accelerated
      atherosclerosis. Clot formation and function are also directly affected by
      insulin resistance and hyperglycaemia, with increased levels of coagulation
      factors and anti-fibrinolytic proteins and a fibrin network that is more
      resistant to lysis, coupled with increased platelet activation.It is well
      recognised that the intensification of glycaemic control leads to a reduction in
      microvascular complications in type 1 and type 2 diabetes; however, the same is
      less clear with macrovascular disease. Several randomised studies have attempted
      to address the effect of short-, medium- and long-term glycaemic control on
      cardiovascular outcomes, with mixed results. The overall interpretation of these
      trials suggests that intensive glycaemic control in patients with a relatively
      short duration of diabetes, without very poor control and with no CVD, might be
      safe and associated with fewer cardiovascular events.This review will summarise
      the effects of hyperglycaemia on the development of atherothrombosis and examine
      key cardiovascular outcome trials following intensive glucose control. 

PMID- 27026401
TI  - First case of successful liver transplantation performed by a Moroccan team.

PMID- 27026402
TI  - A Synthetic Single-Site Fe Nitrogenase: High Turnover, Freeze-Quench (57)Fe
      Mossbauer Data, and a Hydride Resting State.
AB  - The mechanisms of the few known molecular nitrogen-fixing systems, including
      nitrogenase enzymes, are of much interest but are not fully understood. We
      recently reported that Fe-N2 complexes of tetradentate P3(E) ligands (E = B, C)
      generate catalytic yields of NH3 under an atmosphere of N2 with acid and
      reductant at low temperatures. Here we show that these Fe catalysts are
      unexpectedly robust and retain activity after multiple reloadings. Nearly an
      order of magnitude improvement in yield of NH3 for each Fe catalyst has been
      realized (up to 64 equiv of NH3 produced per Fe for P3(B) and up to 47 equiv for
      P3(C)) by increasing acid/reductant loading with highly purified acid. Cyclic
      voltammetry shows the apparent onset of catalysis at the P3(B)Fe-N2/P3(B)Fe-N2(-)
      couple and controlled-potential electrolysis of P3(B)Fe(+) at -45  degrees C
      demonstrates that electrolytic N2 reduction to NH3 is feasible. Kinetic studies
      reveal first-order rate dependence on Fe catalyst concentration (P3(B)),
      consistent with a single-site catalyst model. An isostructural system (P3(Si)) is
      shown to be appreciably more selective for hydrogen evolution. In situ freeze
      quench Mossbauer spectroscopy during turnover reveals an iron-borohydrido-hydride
      complex as a likely resting state of the P3(B)Fe catalyst system. We postulate
      that hydrogen-evolving reaction activity may prevent iron hydride formation from
      poisoning the P3(B)Fe system. This idea may be important to consider in the
      design of synthetic nitrogenases and may also have broader significance given
      that intermediate metal hydrides and hydrogen evolution may play a key role in
      biological nitrogen fixation.

PMID- 27026403
TI  - Erratum to: Spironolactone improves endothelial dysfunction in streptozotocin
      induced diabetic rats.

PMID- 27026406
TI  - Dipole Excitation: A New Method for Mass Analysis with a Quadrupole Mass Filter.
AB  - Trajectory calculations are used to investigate peak shapes and ion transmission
      with a proposed new method of mass analysis with a quadrupole mass filter. Dipole
      excitation is applied to either the x or the y electrodes, or both, to create
      bands of instability within the first stability region. With excitation between
      the y electrodes (near beta y  = 0), ions are removed from the low mass side of a
      peak, and with ion excitation in x (near beta x  = 1), ions are removed from the
      high mass side. The mass resolution can be approximately doubled with
      comparatively little loss in ion transmission. Ion motion in an ideal quadrupole
      field and in the field of a quadrupole constructed with round rods has been
      studied. With an ideal quadrupole field, excitation in y is found to give better
      peak shape and resolution than excitation in x. With quadrupoles constructed with
      round rods, excitation in y is found to remove ions from both the low and high
      mass sides of a peak. The additional higher order multipoles introduced to the
      quadrupole potential by the use of round rods couple the x motion to the y motion
      so that exciting the y motion also excites ions in x. Thus, only excitation in y
      is necessary. Both with an ideal quadrupole field and quadrupoles constructed
      with round rods, the resolution can be increased ca. *2 with little loss of
      transmission. Graphical Abstract ?.

PMID- 27026405
TI  - Curcumin downregulates p38 MAPK-dependent X-ray repair cross-complement group 1
      (XRCC1) expression to enhance cisplatin-induced cytotoxicity in human lung cancer
      cells.
AB  - Cisplatin is a well-studied and widely used chemotherapeutic agent and is
      effective in the treatment of the advanced human non-small cell lung cancer
      (NSCLC). Curcumin is a yellow pigment derived from the rhizome of Curcuma longa
      and has been proved to have antioxidant and antitumor properties. XRCC1 is an
      important scaffold protein involved in base excision repair and plays an
      important role in the development of lung cancer. In this study, we characterize
      the role of curcumin in the cytotoxicity, p38 MAPK activation, and XRCC1
      expression affected by cisplatin in NSCLC cells. We show that curcumin enhanced
      the cytotoxicity induced by cisplatin in two NSCLC cells, A549 and H1703.
      Treatment with cisplatin alone increased XRCC1 mRNA and protein expression
      through p38 MAPK activation. Moreover, SB2023580 (p38 inhibitor) decreased the
      XRCC1 mRNA and protein stability upon cisplatin treatment. Knockdown of XRCC1 in
      NSCLC cells by transfection of XRCC1 siRNA or inactivation of p38 MAPK resulted
      in enhancing the cytotoxicity and cell growth inhibition induced by cisplatin.
      Curcumin inhibited the expression of XRCC1 in cisplatin-exposed NSCLC cells.
      Furthermore, transfection with constitutive active MKK6 or HA-p38 MAPK vectors
      rescued the XRCC1 protein level and also the cell survival suppressed by
      cisplatin and curcumin combination in A549 and H1703 cells. These findings
      suggested that the downregulation of XRCC1 expression by curcumin can enhance the
      chemosensitivity of cisplatin in NSCLC cells. 

PMID- 27026404
TI  - Tempol and perindopril protect against lipopolysaccharide-induced cognition
      impairment and amyloidogenesis by modulating brain-derived neurotropic factor,
      neuroinflammation and oxido-nitrosative stress.
AB  - We aim to evaluate the protective role of the central angiotensin-converting
      enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen
      species (ROS) scavenger tempol, against lipopolysaccharide (LPS)-induced
      cognition impairment and amyloidogenesis in a simulation to Alzheimer's disease
      (AD). Mice were allocated into a control group, an LPS control group (0.8 mg/kg,
      i.p., once), a tempol (100 mg/kg/day, p.o., 7 days) treatment group, and two
      perindopril (0.5 and 1 mg/kg/day, p.o., 7 days) treatment groups. A behavioral
      study was conducted to evaluate spatial and nonspatial memory in mice, followed
      by a biochemical study involving assessment of brain levels of Abeta and BDNF as
      Alzheimer and neuroplasticity markers; tumor necrosis factor-alpha (TNF-alpha),
      nitric oxide end-products (NOx), neuronal nitric oxide synthase (nNOS), and
      inducible nitric oxide synthase (iNOS) as inflammatory markers; and superoxide
      dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and
      nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally,
      histopathological examination of cerebral cortex, hippocampus, and cerebellum
      sections was performed using both routine and special staining. Tempol and
      perindopril improved spatial and nonspatial memory in mice without affecting
      locomotor activity; decreased brain Abeta deposition and BDNF depletion;
      decreased brain TNF-alpha, NOx, nNOS, iNOS, MDA, and NT levels; and increased
      brain SOD and GSH contents, parallel to confirmatory histopathological findings.
      Tempol and perindopril may be promising agents against AD progression via
      suppression of Abeta deposition and BDNF decline, suppression of TNF-alpha
      production, support of brain antioxidant status, and amelioration of oxido
      nitrosative stress and NT production. 

PMID- 27026407
TI  - Sex differences in the intellectual functioning of early school-aged children in
      rural China.
AB  - BACKGROUND: Gender disparities in China are concentrated in poor rural areas and
      among poor households. The difference in intelligence between boys and girls is
      less clear in rural China. The purpose of this paper was to assess sex
      differences in the intellectual function of early school-aged children in rural
      China. METHODS: One thousand seven hundred forty four early school-aged offspring
      of women who had participated in a prenatal supplementation trial with different
      combinations of micronutrients and continued to reside in two rural counties in
      China were followed. We measured their Full-Scale IQ (FSIQ), Verbal Comprehension
      Index (VCI), Working Memory Index (WMI), Perceptual Reasoning Index (PRI) and
      Processing Speed Index (PSI) using the Wechsler Intelligence Scale for Children
      (WISC-IV). Multilevel analyses were used to assess sex differences in
      intellectual functioning in 7-10-year-old children in rural China. RESULTS: Boys'
      adjusted mean FSIQ score was 0.97 points higher (95% CI: -2.22 - 0.28) than that
      of girls. Girls obtained higher mean WMI and PSI scores, with 1.32 points (95%
      CI: 0.14 - 2.51) and 3.10 points (95% CI: 1.82-4.38) higher adjusted means,
      respectively. Boys' adjusted mean VCI and PRI scores were significantly higher
      than those of girls, and the mean differences were 2.44 points (95% CI: 0.95 -
      3.94) and 3.68 points (95% CI: 2.36 - 5.01), respectively. CONCLUSIONS: There is
      no evidence to suggest sex differences in the general intelligence of early
      school-aged children in rural China. However, a difference in general
      intelligence between 10-year-old boys and girls was evident. Girls and boys in
      rural China tended to show different specific cognitive abilities.

PMID- 27026408
TI  - Rape Perpetrators on Trial: The Effect of Sexual Assault-Related Schemas on
      Attributions of Blame.
AB  - Research has consistently shown that jurors are influenced by multiple schemas in
      cases of alleged sexual assault, including offense stereotypes and victim
      stereotypes. These schemas appear to be organized in a hierarchy, as victim
      stereotypicality seems to matter most in acquaintance assaults (counter
      stereotypical offense). However, despite numerous studies demonstrating the
      impact of defendant stereotypes on juror perceptions of guilt for other crimes,
      to date, the impact of stereotypes about defendants (perpetrators) in cases
      involving sexual violence have been overlooked. As such, the current research
      aimed to build on the existing hierarchical schema model by systematically
      examining the influence of perpetrator stereotypes. Following pilot work, mock
      jurors' ( N = 163) read a rape scenario that varied in terms of offense
      stereotypicality (stereotypical, counter-stereotypical), victim stereotypicality
      (stereotypical, counter-stereotypical), and perpetrator stereotypicality
      (stereotypical, counter-stereotypical). Broadly consistent effects of offense
      stereotypicality and victim stereotypicality were observed across the outcome
      measures, such that the victim was perceived more positively and the perpetrator
      more negatively when the victim was described as being stereotypical and when the
      offense was described as stereotypical. However, contrary to past findings, the
      effect of victim stereotypicality did not differ as a function of offense
      stereotypicality. Furthermore, perpetrator stereotypicality did not influence
      perceptions in the stereotypical offense scenario. These findings suggest that
      contrary to the assertions of previous research, there is not a series of
      specific, individual stereotypes that impact attributions of blame, rather, there
      may be one underlying schema about consent that influences perceptions. These
      findings have important implications for how we address the effect of juror-held
      schemas on attributions of blame in cases of sexual assault.

PMID- 27026409
TI  - Inducible Nitric Oxide Synthase Expression in Liver Injury: Liver Protective
      Effects on Primary Rat Hepatocytes.
AB  - BACKGROUND/AIMS: Following injury to the liver, liver cells, including Kupffer
      cells and hepatocytes express inducible nitric oxide synthase (iNOS), followed by
      the production of excess levels of nitric oxide (NO). NO produced by iNOS has
      been found to contribute to liver injury. Treatment of primary cultures of rat
      hepatocytes with the proinflammatory cytokine interleukin (IL)-1beta stimulated
      iNOS expression and NO production. Experiments with this in vitro hepatocyte
      model of liver injury and with in vivo animal models of liver injury have
      demonstrated that drugs showing a liver-protective effect in vivo also inhibited
      the induction of iNOS expression and NO production both in vivo and in vitro.
      Thus, in this in vitro hepatocyte model, the prevention of iNOS expression and NO
      production are considered indicators of liver protection. RESULTS/CONCLUSION:
      This review describes a simple in vitro liver injury model, consisting of IL
      1beta-stimulated cultured hepatocytes, and methods used to analyze the mechanisms
      of action of drugs that inhibit iNOS expression. This in vitro hepatocyte model
      may be used to assess the liver-protective effects of pharmaceutical agents,
      herbal medicines, and certain types of foods.

PMID- 27026410
TI  - Prevalence of human immunodeficiency virus infection in a cohort of tuberculosis
      patients at Metema Hospital, Northwest Ethiopia: a 3 years retrospective study.
AB  - BACKGROUND: Ethiopia is one of the countries that are highly affected by dual
      epidemics of human immunodeficiency virus (HIV) and tuberculosis (TB). HIV
      infection is a known risk factor for the development of active TB and it
      challenges in diagnosis and treatment of TB. Thus, it is essential to determine
      the epidemiology of HIV infection among TB patients to guide clinical actions and
      inform the policy makers. This study was aimed to assess the prevalence of HIV
      infection among TB patients and to describe the associated risk factors for HIV
      seropositivity. METHODS: A retrospective study was conducted on TB registries at
      Metema Hospital directly observed therapy short-course (DOTS) clinic. Binary and
      multivariate logistic regression analysis was used to determine the association
      of HIV seropositivity among TB patients. Odds ratio (OR) and 95% confidence
      intervals (CI) were calculated. P value less than 0.05 was considered as
      statistically significant. RESULTS: Of the total 2096 patients, 2005 (95.7%) were
      tested for HIV. The overall HIV-TB co-infection rate was 20.1% (404), 12.3% (246)
      in males and 7.9% (158) in females. The highest proportion of co-infection rate
      was observed among the patients in the age group of 25-34 years (32.4%) and smear
      negative pulmonary TB patients (59.7%). A declining trend of HIV-TB co-infection
      was observed during the study period, from 22.1% (185) in 2009/10 to 12.8% (52)
      in 2011/12 (X(2) = 17.07, P < 0.001). CONCLUSIONS: This study found that HIV-TB
      co-infection is still high in the Metema area; and occurs more frequently in
      males than females, and among patients in age group of 25-34 years. Thus,
      concerted efforts and interventions methods that target these at risk groups are
      recommended.

PMID- 27026412
TI  - Commentary on "Histone H3F3A and HIST1H3B K27M mutations define two subgroups of
      diffuse intrinsic pontine gliomas with different prognosis and phenotypes".

PMID- 27026411
TI  - NG2, a common denominator for neuroinflammation, blood-brain barrier alteration,
      and oligodendrocyte precursor response in EAE, plays a role in dendritic cell
      activation.
AB  - In adult CNS, nerve/glial-antigen 2 (NG2) is expressed by oligodendrocyte
      progenitor cells (OPCs) and is an early marker of pericyte activation in
      pathological conditions. NG2 could, therefore, play a role in experimental
      autoimmune encephalomyelitis (EAE), a disease associated with increased blood
      brain barrier (BBB) permeability, inflammatory infiltrates, and CNS damage. We
      induced EAE in NG2 knock-out (NG2KO) mice and used laser confocal microscopy
      immunofluorescence and morphometry to dissect the effect of NG2 KO on CNS
      pathology. NG2KO mice developed milder EAE than their wild-type (WT)
      counterparts, with less intense neuropathology associated with a significant
      improvement in BBB stability. In contrast to WT mice, OPC numbers did not change
      in NG2KO mice during EAE. Through FACS and confocal microscopy, we found that NG2
      was also expressed by immune cells, including T cells, macrophages, and dendritic
      cells (DCs). Assessment of recall T cell responses to the encephalitogen by
      proliferation assays and ELISA showed that, while WT and NG2KO T cells
      proliferated equally to the encephalitogenic peptide MOG35-55, NG2KO T cells were
      skewed towards a Th2-type response. Because DCs could be responsible for this
      effect, we assessed their expression of IL-12 by PCR and intracellular FACS. IL
      12-expressing CD11c+ cells were significantly decreased in MOG35-55-primed NG2KO
      lymph node cells. Importantly, in WT mice, the proportion of IL-12-expressing
      cells was significantly lower in CD11c+ NG2- cells than in CD11c+ NG2+ cells. To
      assess the relevance of NG2 at immune system and CNS levels, we induced EAE in
      bone-marrow chimeric mice, generated with WT recipients of NG2KO bone-marrow
      cells and vice versa. Regardless of their original phenotype, mice receiving
      NG2KO bone marrow developed milder EAE than those receiving WT bone marrow. Our
      data suggest that NG2 plays a role in EAE not only at CNS/BBB level, but also at
      immune response level, impacting on DC activation and thereby their stimulation
      of reactive T cells, through controlling IL-12 expression.

PMID- 27026414
TI  - Effects of osmolytes on solvent features of water in aqueous solutions.
AB  - The solvatochromic solvent features of water (dipolarity/polarizability, pi*,
      hydrogen bond donor acidity, alpha, and hydrogen bond acceptor basicity, beta) of
      water have been determined in aqueous solutions of erythritol, glucose, inositol,
      sarcosine, xylitol and urea with concentrations from 0 to ~3 M and higher. The
      concentration effects of the osmolytes on the solvent features of water were
      characterized and compared with those reported previously for sorbitol, sucrose,
      trimethylamine N-oxide (TMAO), and trehalose. The solvent features of water in
      solutions of all osmolytes except TMAO and sarcosine were established to be
      linearly interrelated. It is shown that the concentration effects of essentially
      all nonionic osmolytes depend on osmolytes' lipophilicity, molecular
      polarizability, and polar surface area. It is demonstrated that solubility of
      various compounds in aqueous solutions of glucose, sucrose, sorbitol, and urea of
      varied concentrations may be described in terms of solvent
      dipolarity/polarizability of water in these solutions. Surface tension of aqueous
      solutions of sucrose and sorbitol may also be described in the same terms. The
      relative permittivity of aqueous solutions of glucose and sucrose may be
      described in terms of the solvent hydrogen bond donor acidity of water. It is
      suggested that the effects of nonionic osmolytes on behavior of proteins and
      nucleic acids in aqueous media may be considered in terms of the altered solvent
      features of water instead of "nano-molecular crowding" effect.

PMID- 27026416
TI  - Cardiovascular Drugs and Therapy Celebrates its 30th Year with the Appointment of
      a New Co-Editor-in-Chief.

PMID- 27026413
TI  - A comprehensive study of the genetic impact of rare variants in SORL1 in European
      early-onset Alzheimer's disease.
AB  - The sortilin-related receptor 1 (SORL1) gene has been associated with increased
      risk for Alzheimer's disease (AD). Rare genetic variants in the SORL1 gene have
      also been implicated in autosomal dominant early-onset AD (EOAD). Here we report
      a large-scale investigation of the contribution of genetic variability in SORL1
      to EOAD in a European EOAD cohort. We performed massive parallel amplicon-based
      re-sequencing of the full coding region of SORL1 in 1255 EOAD patients and 1938
      age- and origin-matched control individuals in the context of the European Early
      Onset Dementia (EOD) consortium, originating from Belgium, Spain, Portugal,
      Italy, Sweden, Germany, and Czech Republic. We identified six frameshift variants
      and two nonsense variants that were exclusively present in patients. These
      mutations are predicted to result in haploinsufficiency through nonsense-mediated
      mRNA decay, which could be confirmed experimentally for SORL1 p.Gly447Argfs*22
      observed in a Belgian EOAD patient. We observed a 1.5-fold enrichment of rare non
      synonymous variants in patients (carrier frequency 8.8 %; SkatOMeta p value
      0.0001). Of the 84 non-synonymous rare variants detected in the full
      patient/control cohort, 36 were only detected in patients. Our findings
      underscore a role of rare SORL1 variants in EOAD, but also show a non-negligible
      frequency of these variants in healthy individuals, necessitating the need for
      pathogenicity assays. Premature stop codons due to frameshift and nonsense
      variants, have so far exclusively been found in patients, and their predicted
      mode of action corresponds with evidence from in vitro functional studies of
      SORL1 in AD.

PMID- 27026415
TI  - Everolimus-induced epithelial to mesenchymal transition (EMT) in
      bronchial/pulmonary cells: when the dosage does matter in transplantation.
AB  - BACKGROUND: Everolimus (EVE) is a mammalian target of rapamycin inhibitor (mTOR
      I) widely used in transplantation that may determine some severe adverse events,
      including pulmonary fibrosis. The pathogenic mechanism of mTOR-I-associated
      pulmonary toxicity is still unclear, but epithelial to mesenchymal transition
      (EMT) of bronchial/pulmonary cells may play a role. METHODS: Three cell lines
      human type II pneumocyte-derived A549, normal bronchial epithelial, and bronchial
      epithelial homozygous for the delta F508 cystic fibrosis-causing mutation-were
      treated with EVE or tacrolimus at different concentrations. Real-time polymerase
      chain reaction and immunofluorescence were used to evaluate mRNA and protein
      levels of EMT markers (alpha-SMA, vimentin, fibronectin). Subsequently, in 13 EVE
      and 13 tacrolimus-treated patients we compared the rate of lung fibrosis,
      estimated by an arbitrary pulmonary fibrosis index score (PFIS). RESULTS:
      Biomolecular experiments demonstrated that high doses of EVE (100 nM) up
      regulated EMT markers in all cell lines at both gene- and protein level. High
      concentrations of EVE were also able to reduce the mRNA levels of epithelial
      markers (E-cadherin and ZO-1) and to induce the phosphorylation of AKT. In the in
      vivo part of the study, PFIS was significantly higher in the EVE-group than the
      tacrolimus-group (p = 0.03) and correlated with trough levels (R2 = 0.35).
      CONCLUSIONS: Our data reveal, for the first time, a dose-dependent EVE-induced
      EMT in airway cells. They suggest that clinicians should employ, wherever
      possible, low dosages of mTOR-Is in transplant recipients, assessing periodically
      their pulmonary function.

PMID- 27026418
TI  - The Center for Disease Control and Prevention's (CDC) Youth Violence Prevention
      Centers: Paving the Way to Prevention.

PMID- 27026417
TI  - Difference between apnea-hypopnea index (AHI) and oxygen desaturation index
      (ODI): proportional increase associated with degree of obesity.
AB  - PURPOSE: Obesity is one of the main predisposing factors for obstructive sleep
      apnea (OSA) hypopnea syndrome. It has been described that body mass index (BMI)
      influences the accuracy of oxygen desaturation index (ODI) for the diagnosis of
      OSA by polysomnography (PSG). We analyzed the relationship between traditional
      indicators: apnea-hypopnea index (AHI) and ODI in a population at high risk for
      OSA, by respiratory polygraphy (RP) and PSG. METHODS: This is a retrospective
      study of 1898 patients with suspicion of OSA, from which 1053 underwent RP and
      582 underwent PSG with OSA. We compared results considering gender, age, and
      degree of obesity. RESULTS: This study included 1333 records of patients with OSA
      more than 80 % of whom were overweight or obese. We observed that AHI and ODI
      increased progressively with obesity grade and said increase was associated with
      BMI only in men. The evaluation of the agreement between AHI and ODI found a
      difference between normal weight and obese patients, regardless of gender.
      CONCLUSIONS: Study findings contribute to understand the role of oximetry in the
      diagnosis of OSA in obese patients. Our results were observed using full PSG and
      a simplified home method. The correlation between these indicators could improve
      our clinical interpretation of OSA severity among obese patients when abbreviated
      tests are used.

PMID- 27026419
TI  - Ultrasound power Doppler synovitis is associated with plasma IL-6 in established
      rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVE: Cytokines have an important role in the pathogenesis of
      rheumatoid arthritis (RA). Although plasma levels of IL-6 have been related to
      musculoskeletal ultrasound (MSUS) synovitis in early DMARD-naive RA, there are no
      similar studies in established disease. METHODS: 64 RA patients treated with non
      biological DMARDs and 30 healthy controls were included in this prospective cross
      sectional study. A blood sample was taken before evaluation of disease activity
      (DAS28) and ultrasonography (all tests performed in a blinded fashion). MSUS was
      performed by one of two ultrasound-trained rheumatologists on 10 joints of both
      hands. Gray scale (GS) and pD (power Doppler) synovitis were evaluated using a
      semi-quantitative scale (0-3) in individual joints, and their sum (score 10) was
      calculated. Plasma cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN-gamma, and
      VEGF) were quantified by flow cytometry. RESULTS: Levels of all cytokines,
      excepting VEGF, were significantly higher in RA patients than in controls
      (P?0.05). In RA patients, IL-6, but not other cytokines, correlated positively
      with DAS28 and swollen joint count (P?0.01), as well as with 10-joint pD score,
      and GS and pD of both wrists (P<0.01 for all tests). In multiple linear
      regression, the association of IL-6 with 10-joint pD score was maintained even
      after adjustment for DAS28. However, there was no correlation of IL-6 with tender
      joint count, 10-joint GS score, or presence of erosions. CONCLUSION: We
      demonstrated an association of inflammatory findings on MSUS and plasma IL-6
      independently of DAS28 in established RA.

PMID- 27026420
TI  - Association of seasonal serum 25-hydroxyvitamin D levels with disability and
      relapses in relapsing-remitting multiple sclerosis.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the association of
      serum 25-hydroxyvitamin D (25(OH)D) with disability and frequency of relapses in
      relapsing-remitting multiple sclerosis (MS) patients. SUBJECTS/METHODS: The study
      included 184 patients with relapsing-remitting MS who were receiving immune
      modulating drugs and no vitamin D supplementation. The concentration of 25(OH)D
      was measured in February and August 2014. The level of disability was assessed
      twice according to the Expanded Disability Status Scale (EDSS). The patients were
      divided into two groups: EDSS 0.0-2 and 2.5-4. The control group comprised 58 age
      and sex-matched healthy subjects. The 25(OH)D levels were compared with the
      occurrence of relapses and the level of disability. RESULTS: Mean serum 25(OH)D
      concentrations were significantly lower in winter in both MS patients and
      controls. Winter level of 25(OH)D was significantly lower in severe MS cases
      (EDSS 2.5-4.0) than in mild cases (EDSS 0.0-2.0) (P=0.022), and in the controls
      (P=0.008), especially in females (r=0.38, P=0.0015). Logistic regression analysis
      showed the winter serum 25(OH)D was significantly associated with MS (odds ratio
      0.925; 95% confidence interval, 0.822-0.970). Serum 25(OH)D levels were
      significantly lower in MS patients with relapses than in those without relapses
      both in winter, and in summer. CONCLUSIONS: Hypovitaminosis D was more prevalent
      during winter than summer, both in the sample group and the control, especially
      in female MS patients with higher levels of disability. Low vitamin D levels are
      associated with a more severe course of disease and an increased number of
      relapses.

PMID- 27026421
TI  - Vitamin D and vitamin B12 deficiencies are common in patients with midgut
      carcinoid (SI-NET).
AB  - BACKGROUND/OBJECTIVES: Patients with small intestinal neuroendocrine tumours (SI
      NET) often have diarrhoea from hormonal overproduction, surgery and medical
      treatment, leading to malabsorption of bile salts, fats, vitamin B12 and fat
      souble vitamins. This could lead to malnutrition. SUBJECTS/METHODS: We assessed
      nutritional status in 50 consecutive out patients with disseminated SI-NET, 25
      patients in each cohort. The first cohort was descriptive and the second cohort
      supplemented with vitamin D, B12 and calcium. Vitamin D deficiency was defined as
      <50 nmol/l. All patients were assessed by clinical chemistry and dual-energy X
      ray absorptiometry (DXA) and interviewed about weight changes, appetite,
      gastrointestinal disorders, sunhabits and the use of supplements. RESULTS: In the
      first cohort, 29% of the patients were severely and 17% moderately vitamin D
      deficient. In patients without prior substitution, 32% had subnormal vitamin B12
      levels. Seventy-six percent had low bone density. In the second cohort with
      vitamin and mineral supplementation, none had severe vitamin D deficiency, but
      28% had moderate deficiency. No patient had subnormal vitamin B12 levels. Sixty
      percent had low bone density. The serum levels of vitamin D and B12 were higher
      and parathyroid hormone (PTH) lower in the second cohort compared with the first
      cohort (P?0,022). Vitamin D and PTH were negatively correlated, r=-30, P=?0.036.
      CONCLUSIONS: Low serum levels of vitamin D and vitamin B12, and low bone density
      are common in patients with disseminated SI-NET. Supplementation of vitamin D,
      B12 and calcium resulted in higher serum levels of vitamins, lower PTH levels and
      diminished severe vitamin D deficiency and is thus recommended as standard care.

PMID- 27026422
TI  - Inhibition of the glycaemic response by onion: a comparison between lactose
      tolerant and lactose-intolerant adults.
AB  - This pilot study compared inhibition of the glycaemic response to glucose by a
      dietary source of quercetin glucosides (onion) in lactose-tolerant adults (n=12)
      and lactose-intolerant adults (n=12). We hypothesised that lactose-intolerant
      people (who do not express lactase) will retain intact quercetin glucosides that
      can inhibit glucose uptake via the glucose transporter SGLT1, whereas lactose
      tolerant people (who do express lactase) will hydrolyse quercetin glucosides to
      free quercetin that does not inhibit glucose uptake. In a glucose tolerance test,
      reduction in peak glucose levels by an onion meal was higher in lactose
      intolerant people than in lactose-tolerant people (44.2 versus 19.3%, P=0.04).
      Incremental area under the blood glucose curve was reduced more in lactose
      intolerant people, but was not statistically significant (54.5 versus 42.1%,
      P=0.42). A diet containing quercetin glucosides may be of greater benefit for
      glycaemic control in lactose-intolerant people than in lactose-tolerant people.

PMID- 27026423
TI  - Ethnic admixture affects diabetes risk in native Hawaiians: the Multiethnic
      Cohort.
AB  - BACKGROUND/OBJECTIVES: Obesity and diabetes rates are high in Native Hawaiians
      (NHs) who commonly have mixed ancestries. People of Asian ancestry experience a
      high risk of type 2 diabetes despite the relatively low body weight. We evaluated
      the impact of ethnic admixture on diabetes risk among NHs in the Multiethnic
      Cohort (MEC). SUBJECTS/METHODS: On the basis of self-reports, 11 521 eligible men
      and women were categorized into NH/white, NH/other, NH alone, NH/Asian and the
      most common three ancestry admixture, NH/Chinese/white. Cox proportional hazard
      ratios (HRs) and 95% confidence intervals (CIs) were calculated with the NH/white
      category as the reference group; covariates included known confounders-that is,
      body mass index (BMI), dietary and other lifestyle factors. RESULTS: The NH alone
      category had the highest proportion of overweight and obese individuals and the
      NH/Asian category the lowest proportion. During 12 years of follow-up after
      cohort entry at 56 years, 2072 incident cases were ascertained through
      questionnaires and health plan linkages. All NH categories had higher HRs than
      the NH/white category before and after adjustment for BMI. In the fully adjusted
      models, the NH/Asian category showed the highest risk (HR=1.45; 95% CI: 1.27
      1.65), followed by NH/other (HR=1.20; 95% CI: 1.03-1.39), NH/Chinese/white
      (HR=1.19; 95% CI: 1.04-1.37) and NH alone (HR=1.19; 95% CI: 1.03-1.37). The
      elevated risk by Asian admixture was more pronounced in normal weight than
      overweight/obese individuals. CONCLUSIONS: These findings indicate that Asian
      admixture in NHs is associated with a higher risk for type 2 diabetes independent
      of known risk factors and suggest a role for ethnicity-related genetic factors in
      the development of this disease.

PMID- 27026424
TI  - Body composition in overweight and obese women postpartum: bioimpedance methods
      validated by dual energy X-ray absorptiometry and doubly labeled water.
AB  - BACKGROUND/OBJECTIVES: Obesity, pregnancy and lactation all affect body
      composition. Simple methods to estimate body composition are useful in clinical
      practice and to evaluate interventions. In overweight and obese lactating women,
      such methods are not fully validated. The objective of this study was to validate
      the accuracy and precision of bioimpedance spectroscopy (BIS) by Xitron 4200 and
      8-electrode multifrequency impedance (multifrequency bioimpedance analysis,
      MFBIA) by Tanita MC180MA with the reference methods dual energy X-ray
      absorptiometry (DXA) and doubly labeled water (DLW) for the assessment of body
      composition in 70 overweight and obese women postpartum. SUBJECTS/METHODS: The
      LEVA-study (Lifestyle for Effective Weight loss during lactation) consisted of an
      intervention and follow-up with three assessments at 3, 6 and 15 months
      postpartum, which made possible the validation of both accuracy and precision.
      Mean differences between methods were tested by a paired t-test and Bland-Altman
      plots for systematic bias. RESULTS: At baseline, BIS and MFBIA underestimated fat
      mass (FM) by 2.6+/-2.8 and 8.0+/-4.2 kg compared with DXA (P<0.001) but without
      systematic bias. BIS and MFBIA overestimated total body water (TBW) by 2.4+/-2.2
      and 4.4+/-3.2 kg (P<0.001) compared with DLW, with slight systematic bias by BIS.
      BIS correctly estimated muscle mass without systematic bias (P>0.05). BIS
      overestimated changes in TBW (P=0.01) without systematic bias, whereas MFBIA
      varied greatly and with systematic bias. CONCLUSIONS: BIS underestimates mean FM
      compared with DXA but can detect mean changes in body composition, although with
      large limits of agreement. BIS both accurately and precisely estimates muscle
      mass in overweight and obese women postpartum. MFBIA underestimates FM and
      overestimates TBW by proprietary equations compared with DXA and DLW.

PMID- 27026425
TI  - LMS tables for waist circumference and waist-height ratio in Colombian adults:
      analysis of nationwide data 2010.
AB  - BACKGROUND/OBJECTIVES: Indices predictive of central obesity include waist
      circumference (WC) and waist-to-height ratio (WHtR). These data are lacking for
      Colombian adults. This study aims at establishing smoothed centile charts and LMS
      tables for WC and WHtR; appropriate cutoffs were selected using receiver
      operating characteristic analysis based on data from the representative sample.
      SUBJECTS/METHODS: We used data from the cross-sectional, national representative
      nutrition survey (ENSIN, 2010). A total of 83 220 participants (aged 20-64) were
      enroled. Weight, height, body mass index (BMI), WC and WHtR were measured and
      percentiles calculated using the LMS method (L (curve Box-Cox), M (curve median),
      and S (curve coefficient of variation)). Receiver operating characteristics curve
      analyses were used to evaluate the optimal cutoff point of WC and WHtR for
      overweight and obesity based on WHO definitions. RESULTS: Reference values for WC
      and WHtR are presented. Mean WC and WHtR increased with age for both genders. We
      found a strong positive correlation between WC and BMI (r=0.847, P< 0.01) and
      WHtR and BMI (r=0.878, P<0.01). In obese men, the cutoff point value is 96.6 cm
      for the WC. In women, the cutoff point value is 91.0 cm for the WC. Receiver
      operating characteristic curve for WHtR was also obtained and the cutoff point
      value of 0.579 in men, and in women the cutoff point value was 0.587. A high
      sensitivity and specificity were obtained. CONCLUSIONS: This study presents first
      reference values of WC and WHtR for Colombians aged 20-64. Through LMS tables for
      adults, we hope to provide quantitative tools to study obesity and its
      complications.

PMID- 27026426
TI  - Association between folate status and cervical intraepithelial neoplasia.
AB  - BACKGROUND/OBJECTIVES: To investigate the effect of folate status on cervical
      intraepithelial neoplasia (CIN) progression and its relationship with high-risk
      human papillomavirus (hrHPV). SUBJECTS/METHODS: We evaluated 20 000 sexually
      active women aged <65 years in Yangqu County by using a questionnaire; the
      subjects were also screened using the ThinPrep cytologic test (TCT). Patients
      with abnormal TCT results (other than glandular cell abnormalities) who were
      willing to provide informed consent were further diagnosed using colposcopy and
      histopathological examination. We investigated 247 cases of low-grade cervical
      squamous intraepithelial lesions (LSIL), 125 cases of high-grade cervical
      squamous intraepithelial lesions (HSIL) and 877 controls. A 24-item food
      frequency questionnaire was filled out by the investigator to estimate the
      consumption of dietary folate. Positivity for hrHPV from residual exfoliated
      cervical cells was tested; serum folate was also measured. RESULTS: The hrHPV
      infection rate in HSIL patients (77.6%) was higher than that in LSIL (33.2%) and
      control (32.0%) patients. Dietary folate intakes in controls, LSIL and HSIL were
      306.9+/-176.6, 321.8+/-168.0 and 314.7+/-193.8 MUg/kcal, respectively. The levels
      of serum folate in controls, LSIL and HSIL were 18.2+/-7.9, 15.9+/-7.1 and 14.3+/
      7.5 nmol/l, respectively. Increased CIN correlated with higher rates of hrHPV
      infection and lower levels of serum folate. CONCLUSIONS: Low levels of serum
      folate may increase the risk of CIN progression. Furthermore, potential synergy
      may exist between low serum folate levels and hrHPV infection to promote CIN
      development.

PMID- 27026427
TI  - Effect of whey protein on blood lipid profiles: a meta-analysis of randomized
      controlled trials.
AB  - Previous studies have suggested that whey supplementation may have beneficial
      effects on lipid profiles, although results were inconsistent. A literature
      search was performed in March 2015 for randomized controlled trials observing the
      effects of whey protein and its derivatives on circulating levels of
      triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol
      (LDL-C) and high-density lipoprotein cholesterol (HDL-C). A meta-analysis was
      subsequently conducted. The meta-analysis results of 13 trials showed that whey
      supplementation significantly reduced the circulating TG level by 0.11 mmol/l
      (95% CI: -0.21, 0 mmol/l), whereas the whey protein had no effects on circulating
      TC (-0.11 mmol/l, 95% CI: -0.27, 0.05 mmol/l), LDL-C (-0.08 mmol/l, 95% CI: 
      0.23, 0.07 mmol/l) and HDL-C (0.01 mmol/l, 95% CI: -0.04, 0.05 mmol/l). Subgroup
      analysis showed that significant TG reduction disappeared in participants with
      low body mass index, low supplemental whey dose or under exercise training/energy
      restriction during the trial. No evidence of heterogeneity across studies and
      publication bias was observed. In conclusion, our findings demonstrated that the
      effects of whey protein supplementation were modest, with an overall lowering
      effect on TG but no effect on TC, LDL-C and HDL-C.

PMID- 27026428
TI  - Bioimpedance spectroscopy in the infant: effect of milk intake and extracellular
      fluid reservoirs on resistance measurements in term breastfed infants.
AB  - BACKGROUND/OBJECTIVES: Bioimpedance spectroscopy is an accurate non-invasive
      method for measuring body composition in adults, but in infants it requires
      further testing and validation. Of the few studies of bioimpedance conducted in
      infants, none have comprehensively investigated the effect of milk intake volume.
      This study assessed the effect of the milk intake, feed duration and the volume
      of the infant's stomach and bladder on the resistance values pre-/post-feed to
      establish the feasibility of using these values interchangeably during data
      collection. SUBJECTS/METHODS: Forty-eight breastfeeding infants were measured at
      2, 5, 9 and/or 12 months (n=62 sessions) within 1-2 min before the start and
      after the end of breastfeed. Median (IQR) time between measurements was 24 (20.0
      30.0) min. Resistance measurements at 0 and 50 kHz, and infinite frequency (R0,
      R50 and Rinf) and resistance of intracellular water (Ricw) were analysed with
      customised infant settings. Milk intake was measured by test weights. Free-water
      volumes and free-water change were determined from stomach and bladder volumes
      calculated from ultrasound images. RESULTS: Small pre-to-post-feed changes
      (median (IQR): R0 -3.7 (-14.8, 14.3); R50 0.3 (-10.4, 15.0); Rinf 2.8 (-13.3,
      35.5); Ricw 20.8 (-98.1, 290.9)) were not significantly different from zero (R0:
      P=0.92; R50: P=0.48; Rinf: P=0.32; Ricw: P=0.097). No significant effect of milk
      intake or free-water change was detected. CONCLUSIONS: The lack of consistent
      change in resistance across a breastfeed provides flexibility in the timing of
      measurements of infants in the research setting, such that typically pre- and
      post-feed measures of resistance can be used interchangeably.

PMID- 27026429
TI  - Modelling human height and weight: a Bayesian approach towards model comparison.
AB  - BACKGROUND/OBJECTIVES: Given the availability of large longitudinal data sets on
      human height and weight, different modelling approaches are at hand to access
      quantities of interest relating to important diagnostic aims. SUBJECTS/METHODS:
      Statistical modelling frameworks for longitudinal data on human height and weight
      have to consider the issues of individual heterogeneity and time dependence to
      provide an accurate statistical characterisation. Further, missing values
      inevitably occurring within longitudinal data sets have to be addressed
      adequately to allow for valid inference. The Bayesian framework is illustrated to
      facilitate stringent comparison of available non-nested model frameworks
      addressing these issues using simulated and empirical data sets. RESULTS:
      Comparing random-effects and fixed-effects modelling approaches with the Preece
      Baines (PB) model reveals that, for simulated data, the Bayesian approach towards
      model comparison is effective in discriminating between different model
      specifications. With regard to analysis of 14 longitudinal data sets, the
      implicit trade-off between model fit, that is, description of the data, and a
      parsimonious parameterisation favouring prediction is often best addressed via
      the PB model. CONCLUSIONS: The Bayesian approach is illustrated to allow for
      effective comparison in case model specifications for longitudinal data are not
      linked directly via parametric restrictions.

PMID- 27026431
TI  - Examining the clinical course of genotype 1 chronic hepatitis C patients treated
      with the cosmos regimen: including patients with advanced liver disease and East
      Asian ancestry.
AB  - BACKGROUND/OBJECTIVES: The COSMOS study was a phase 2a clinical trial that showed
      high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side
      effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF).
      Given the small number of patients treated with the SIM + SOF regimen in the
      COSMOS trial, there is uncertainty regarding the efficacy and safety of this
      combination therapy. We now report our experience with the COSMOS regimen in the
      multiethnic population of Hawaii, including patients of East Asian ancestry and
      with decompensated cirrhosis. METHODS: This study is a retrospective review of
      138 patients treated with a fixed dose regimen of SIM 150 mg and SOF 400 mg daily
      at a single referral center. We collected data on demographics, side effects,
      laboratory studies and sustained virological response (SVR). Statistical analysis
      was performed with Stata v8.2 software. RESULTS: Baseline characteristics of the
      138 patients initiated with SIM + SOF therapy were: 68.8 % cirrhotic (22.1 % of
      those Child-Pugh Class B), 37 % Asian, 11.6 % Pacific Islander, 63 % male, mean
      age 61.3 +/- 7.8 years, mean BMI 27.8 +/- 6.1 kg/m(2), 26.8 % diabetic, 63.8 %
      genotype 1a, 44.9 % previously treatment experienced. A total of 100 % of
      patients that completed therapy (n = 137) had undetectable viral loads at end of
      treatment (EOT). Twelve patients relapsed post-treatment resulting in an overall
      12 week SVR (SVR12) rate of 89.1 %. 95 % of decompensated cirrhotic patients
      achieved SVR12, compared to 85.3 % of compensated cirrhotic patients and 93 % of
      non-cirrhotic patients. 92 % of Asian patients achieved SVR12 compared to 87.5 %
      in non-Asian patients. There were no statistically significant differences in
      SVR12 between treatment naive and treatment experienced patients (86.8 vs 91.9
      %). 87.5 % of post-transplant patients achieved SVR12. The main side effects were
      headache 16.2 %, fatigue 24.2 %, pruritis 14.1 %; none were >grade 2 in severity.
      There were no differences in side effect profiles of patients with decompensated
      cirrhosis. Pruritis only was statistically significant between Asians and non
      Asians (22 vs 5.7 %). Trends toward improvement in platelet counts and total
      bilirubin were noted at 12-weeks post treatment, while improvement in albumin in
      cirrhotic patients reached statistical significance (3.77-4.01 mg/dL, p =
      0.0108). CONCLUSIONS: The 12-week fixed dose course of SIM + SOF was well
      tolerated in a multiethnic population of primarily cirrhotic patients, including
      those with decompensated disease. This real world trial achieved SVR12 rates
      comparable to the COSMOS data. Higher incidence of adverse side effects was not
      observed with an exception of higher rate of pruritis in Asians. The increase in
      albumin in cirrhotic patients was statistically significant and suggested early
      improvement in synthetic function following viral eradication. Higher BMI (>=30
      kg/m(2)) was the only factor that correlated with post-treatment relapse by
      multivariate analysis.

PMID- 27026430
TI  - Food fortification for bone health in adulthood: a scoping review.
AB  - Food fortification can deliver essential micronutrients to large population
      segments without modifications in consumption pattern, suggesting that fortified
      foods may be formulated for populations at risk for fragility fractures. This
      scoping review determined the extent to which randomized controlled studies have
      been carried out to test the impact of fortified foods on bone outcomes,
      searching PubMed for all studies using the terms 'fortified AND bone', and
      'fortification AND bone'. Studies were restricted to English language, published
      between 1996 and June 2015. From 360 articles, 24 studies met the following
      criteria: human study in adults ?18 years (excluding pregnancy or lactation);
      original study of a fortified food over time, with specific bone outcomes
      measured pre- and post intervention. Six studies involved adults <50 years; 18
      involved adults ?50 years. Singly or in combination, 17 studies included calcium
      and 16 included vitamin D. There were 1 or 2 studies involving either vitamin K,
      magnesium, iron, zinc, B-vitamins, inulin or isoflavones. For adults <50 years,
      the four studies involving calcium or vitamin D showed a beneficial effect on
      bone remodeling. For adults ?50 years, n=14 provided calcium and/or vitamin D,
      and there was a significant bone turnover reduction. No consistent effects were
      reported in studies in which addition of vitamin K, folic acid or isoflavone was
      assessed. Results from this scoping review indicate that up to now most studies
      of fortification with bone health have evaluated calcium and/or vitamin D and
      that these nutrients show beneficial effects on bone remodeling.

PMID- 27026432
TI  - Crystallographic orientation of the c-axis of biological apatite as a new index
      of the quality of subchondral bone in knee joint osteoarthritis.
AB  - The aim of the present study was to investigate the preferred orientation of
      biological apatite (BAp) as a new index of the quality of subchondral bone (SB)
      in knee joint osteoarthritis (OA). Ten OA and five normal knee joints were
      obtained. Thickness, quantity and bone mineral density (BMD) of SB were analyzed
      at the medial condyle of the femur in dry conditions by peripheral quantitative
      computed tomography. In addition, the preferred crystallographic orientation of
      the c-axis of BAp was evaluated as bone quality parameter using a microbeam X-ray
      diffractometer technique. BMD and thickness of SB were significantly increased in
      OA specimens compared to normal knee specimens (P < 0.01), and the preferred
      orientation of the c-axis of BAp along the normal direction of SB surface was
      significantly higher in OA specimens (P < 0.01), reflecting the change in stress
      of concentration in the pathological portion without cartilage. SB sclerosis in
      OA results in both proliferation of bone tissues and enhanced degree of
      preferential alignment of the c-axis of BAp. Our findings could have major
      implications for the diagnosis of clinical studies, including pathologic
      elucidation in OA.

PMID- 27026433
TI  - Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant
      bone microstructure in obese insulin-resistant rats.
AB  - Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves
      insulin resistance and obesity-associated metabolic disorders. However,
      concomitant activation of peroxisome proliferator-activated receptor-gamma by FGF
      21 makes bone susceptible to osteopenia and fragility fracture. Since an increase
      in body weight often induced adaptive change in bone by making it resistant to
      fracture, it was unclear whether FGF-21 would still induce bone defects in
      overweight rats. Therefore, the present study aimed to investigate bone
      microstructure and its mechanical properties in high fat diet (HF)-fed rats
      treated with 0.1 mg/kg/day FGF-21. Eighteen male rats were divided into two
      groups to receive either a normal diet or HF for 12 weeks. HF rats were then
      divided into two subgroups to receive either vehicle or FGF-21 for 4 weeks. The
      results showed that HF led to obesity, dyslipidemia and insulin resistance, as
      indicated by hyperinsulinemia with euglycemia. In HF rats, there was an increase
      in tibial yield displacement (an indicator of ability to be deformed without
      losing toughness, as determined by 3-point bending) without changes in tibial
      trabecular volumetric bone mineral density (vBMD) or cortical bone parameters,
      e.g., cortical thickness and bone area. FGF-21 treatment strongly improved the
      metabolic parameters and increased insulin sensitivity in HF rats. However, FGF
      21-treated HF rats showed lower yield displacement, trabecular vBMD, trabecular
      bone volume, trabecular thickness, and osteoblast surface compared with vehicle
      treated HF rats. These findings suggest that, despite being a potent antagonist
      of insulin resistance and visceral fat accumulation, FGF-21 is associated with
      bone defects in HF rats.

PMID- 27026434
TI  - Bone metabolism dysfunction mediated by the increase of proinflammatory cytokines
      in chronic HIV infection.
AB  - Despite the efficacy of antiretroviral therapy (ART) on the control of viral
      replication, the current challenge is to decrease the chronic inflammatory status
      and toxicity of the antiretroviral drugs that contribute to increase the risk of
      metabolic complications. To verify the influence of proinflammatory cytokines on
      bone metabolism mediated by chronic HIV infection, a cross-sectional study was
      conducted with 50 HIV-infected adult men treated or not treated with ART. Dual
      energy X-ray absorptiometry (DXA) was performed to assess bone mineral density.
      Biochemical analysis were performed of IL-6, TNF-alpha, osteocalcin, PTH, 25-OH
      D, total calcium, albumin, 24 h urinary calcium, and urinary deoxypyridinoline.
      The participants not treated with ART exhibited higher values of IL-6 and TNF
      alpha than the participants treated with ART for more than 2 years. The TNF-alpha
      values were higher in the participants treated with ART for <2 years than in
      participants treated with ART for more than 2 years (p < 0.05). The increased
      values of urinary deoxypyridinoline indicated a high reabsorptive activity of
      bone tissue in all groups, with a significant difference between the participants
      not treated with ART and the participants treated with ART for <2 years. Through
      the DXA we found a bone mass reduction in all bone sites in each group. The
      increase in production of proinflammatory cytokines, most notably in the viremic
      group, demonstrated the ability to stimulate osteoclast activity and subsequently
      affect bone mass. The reduction of bone mineral density was observed in all bone
      sites, principally for the groups receiving antiretroviral treatment.

PMID- 27026435
TI  - Location of fractures and the characteristics of patients with atypical femoral
      fractures: analyses of 38 Japanese cases.
AB  - The purpose of this study was to determine fracture location and the
      characteristics of patients with atypical femoral fractures (AFFs). We studied 38
      AFFs in 34 patients admitted to our institution between November 2007 and July
      2013. The diagnostic criteria for the AFFs were based on 2014 American Society of
      Bone and Mineral Research guidelines. We classified the fracture location as
      proximal, middle, or distal to trisect the femoral diaphysis from just distal to
      the lesser trochanter to just proximal to the supracondylar flare. Bowing was
      defined as a line through the inside of the tip of the great trochanter and a
      condylar center that was outside the medullary cavity. We investigated the
      fracture's location, existence of coronal bowing, and bisphosphonates (BPs),
      glucocorticoids (GCs), and proton pump inhibitors therapy. We analyzed
      associations between fracture location and demographic and clinical factors.
      Twelve fractures were proximal, 25 were middle, and one was distal. Nineteen
      limbs showed femoral bowing. Thirty-one patients received BP treatment-20
      patients received alendronic acid, eight risedronic acid, and three minodronic
      acid. Fourteen patients received a GC, and 16 received a proton pump inhibitor.
      There was a significant association between coronal bowing and middle fracture
      locations, GC therapy and proximal fracture locations, and older age and middle
      fracture locations. Tall height and heavy weight had an association with proximal
      fracture location, and short height and light weight had an association with
      middle fracture location. In conclusion, we provide evidence supporting a causal
      relationship between BP-related severely suppressed bone turnover and AFFs. We
      also provide evidence supporting additional influences from altered distribution
      of mechanical stress with femoral bowing and various factors, such as GC therapy,
      age, body weight, and height, which might negatively affect bone intensity and
      quality and result in fracture.

PMID- 27026436
TI  - The Role of Intraoperative Pathologic Assessment in the Surgical Management of
      Ductal Carcinoma In Situ.
AB  - BACKGROUND: Re-excision surgeries for the treatment of ductal carcinoma in situ
      (DCIS) put a strain on patients and healthcare resources; however, intraoperative
      pathologic assessment of DCIS may lead to a reduction in these additional
      surgeries. This study examined the relationship between intraoperative pathologic
      assessment and subsequent operations in patients with a diagnosis of DCIS.
      METHODS: Surveillance, Epidemiology, and End Results-Medicare patients diagnosed
      with DCIS from 1999 to 2007 who initially underwent partial mastectomy, without
      axillary surgery, were included in this study. Use of intraoperative frozen
      section or touch preparation during the initial surgery was assessed.
      Multivariable logistic regression was used to describe the relationship between
      the use of intraoperative pathologic assessment and any subsequent mastectomy or
      partial mastectomy within 90 days of the initial partial mastectomy. RESULTS: Of
      8259 DCIS patients, 3509 (43 %) required a second surgery, and intraoperative
      pathologic assessment was performed for 2186 (26 %). Intraoperative pathologic
      assessment had no statistically significant effect on whether or not a subsequent
      breast surgery occurred (adjusted odds ratio 1.07, 95 % confidence interval 0.95
      1.21; p = 0.293). Patient residence in a rural area, tumor size >=2 cm, and
      poorly differentiated tumor grade were associated with a greater likelihood of
      subsequent surgery, while age 80 years and older was associated with a lower
      likelihood of subsequent surgery. CONCLUSIONS: The use of intraoperative frozen
      section or touch preparation during partial mastectomy from 1999 to 2007 was not
      associated with a reduction in subsequent breast operations in women with DCIS.
      These results highlight the need to identify cost-effective tools and strategies
      to reduce the need for additional surgery in patients with DCIS.

PMID- 27026437
TI  - Racial Disparities in Initial Presentation of Benign Thyroid Disease for
      Resection.
AB  - BACKGROUND: Racial disparities exist in thyroidectomy outcomes. One contributing
      factor may be the disease state upon presentation to a surgeon. Minorities with
      thyroid cancer present at a later disease stage and with larger tumors. This
      relationship has not been examined for benign thyroid disease. We sought to
      examine the association between race, referral patterns, and disease severity for
      benign thyroid conditions. METHODS: We analyzed all patients receiving a
      thyroidectomy for benign disease in our institutional endocrine surgery registry.
      Patient demographics, disease history, disease severity, and postoperative
      outcomes were investigated. Univariate analysis compared black and white
      patients. Multivariable linear regression examined the relationship between race
      and time to surgical referral. RESULTS: Of the 1189 patients studied, the
      majority (86.0 %) were white. Black and white patients differed in median income
      and reason for referral. When compared with white patients, black patients more
      commonly presented with compressive symptoms (black: 45.0 % vs. white: 21.2 %, p
      < .01) and dysphagia (19.0 % vs. 10.1 %, p < .01), and after a longer disease
      duration [black: median 0 years (interquartile ratio, IQR, 0-5) vs. white: 0
      years (IQR, 0-2)]. Blacks also had larger glands than white [median 71 grams
      (IQR, 33.5-155.3) vs. 24.3 grams (IQR, 15.0-50.2)]. With the exception of
      reintubation rate, there were no differences in postoperative outcomes.
      CONCLUSIONS: Black patients with benign thyroid conditions have a longer time to
      surgical referral and present for surgical evaluation with more severe disease
      than white patients. Identification of these disparities is the first step in
      eliminating differences in patient care.

PMID- 27026439
TI  - Bifocality versus trifocality.

PMID- 27026438
TI  - Multi-walled carbon nanotube induces nitrative DNA damage in human lung
      epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation.
AB  - BACKGROUND: Carbon nanotube (CNT) is used for various industrial purposes, but
      exhibits carcinogenic effects in experimental animals. Chronic inflammation in
      the respiratory system may participate in CNT-induced carcinogenesis. 8
      Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed during inflammation. We
      have previously reported that multi-walled CNT (MWCNT) induced 8-nitroG formation
      in lung epithelial cells and this process involved endocytosis. To clarify the
      mechanism of CNT-induced carcinogenesis, we examined the role of Toll-like
      receptor (TLR) 9, which resides in endosomes and lysosomes, in 8-nitroG formation
      in human lung epithelial cell lines. METHODS: We performed immunocytochemistry to
      examine 8-nitroG formation in A549 and HBEpC cells treated with MWCNT with a
      length of 1-2 MUm (CNT-S) or 5-15 MUm (CNT-L) and a diameter of 20-40 nm. We
      examined inhibitory effects of endocytosis inhibitors, small interfering RNA
      (siRNA) for TLR9, and antibodies against high-mobility group box-1 (HMGB1) and
      receptor for advanced glycation end-products (RAGE) on 8-nitroG formation. The
      release of HMGB1 and double-stranded DNA (dsDNA) into the culture supernatant
      from MWCNT-treated cells was examined by ELISA and fluorometric analysis,
      respectively. The association of these molecules was examined by double
      immunofluorescent staining and co-immunoprecipitation. RESULTS: CNT-L
      significantly increased 8-nitroG formation at 0.05 MUg/ml in A549 cells and its
      intensity reached a maximum at 1 MUg/ml. CNT-L tended to induce stronger
      cytotoxicity and 8-nitroG formation than CNT-S. Endocytosis inhibitors, TLR9
      siRNA and antibodies against HMGB1 and RAGE largely reduced MWCNT-induced 8
      nitroG formation. MWCNT increased the release of HMGB1 and dsDNA from A549 cells
      into culture supernatant. The culture supernatant of MWCNT-exposed cells induced
      8-nitroG formation in fresh A549 cells. Double immunofluorescent staining and co
      immunoprecipitation showed that TLR9 was associated with HMGB1 and RAGE in
      lysosomes of MWCNT-treated cells. CONCLUSIONS: MWCNT induces injury or necrosis
      of lung epithelial cells, which release HMGB1 and DNA into the extracellular
      space. The HMGB1-DNA complex binds to RAGE on neighboring cells and then CpG DNA
      is recognized by TLR9 in lysosomes, leading to generation of nitric oxide and 8
      nitroG formation. This is the first study demonstrating that TLR9 and related
      molecules participate in MWCNT-induced genotoxicity and may contribute to
      carcinogenesis.

PMID- 27026440
TI  - Trocar anterior chamber maintainer: Improvised infusion technique.
AB  - We present an improvised technique of infusion that uses a trocar cannula as an
      anterior chamber maintainer (ACM). Although routinely used in posterior segment
      surgery, the trocar cannula has been infrequently used in complex anterior
      segment procedures. The trocar ACM creates a transconjunctival biplanar wound of
      appropriate size that is self-sealing and overcomes the shortcomings of an ACM,
      such as spontaneous extrusion and forced introduction into the eye from
      variability in the size of the corneal paracentesis incision. Constant infusion
      inflow through the trocar ACM is used to maintain positive intraocular pressure
      through a self-sealing sclerotomy incision at the limbus. FINANCIAL DISCLOSURE:
      No author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 27026441
TI  - Intraoperative intracameral pilocarpine after capsular tension ring and
      capsule/iris hook insertion in pediatric eyes with subluxated cataract.
AB  - Capsular tension rings and iris hooks have proved to be useful devices in
      cataract surgery in cases of zonular weakness and dialysis. We describe the use
      of intracameral pilocarpine-induced pupillary miosis to couple the iris and the
      capsulorhexis edge with iris hooks during phacoemulsification in pediatric cases
      with posttraumatic subluxated cataractous lens. The coupled iris and capsule act
      as a single unit, eliminating the space between them and significantly reducing
      the possibility of vitreous or ophthalmic viscosurgical device passing through
      the zonular defect. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 27026442
TI  - Bilateral implantation of +2.5 D multifocal intraocular lens and contralateral
      implantation of +2.5 D and +3.0 D multifocal intraocular lenses: Clinical
      outcomes.
AB  - PURPOSE: To assess the clinical visual outcomes of bilateral implantation of
      Restor +2.5 diopter (D) multifocal intraocular lenses (IOLs) and contralateral
      implantation of a Restor +2.5 D multifocal IOL in the dominant eye and Restor
      +3.0 D multifocal IOL in the fellow eye. SETTING: Multicenter study at 8
      investigative sites. DESIGN: Prospective randomized parallel-group patient-masked
      2-arm study. METHODS: This study comprised adults requiring bilateral cataract
      extraction followed by multifocal IOL implantation. The primary endpoint was
      corrected intermediate visual acuity (CIVA) at 60 cm, and the secondary endpoint
      was corrected near visual acuity (CNVA) at 40 cm. Both endpoints were measured 3
      months after implantation with a noninferiority margin of Delta = 0.1 logMAR.
      RESULTS: In total, 103 patients completed the study (53 bilateral, 50
      contralateral). At 3 months, the mean CIVA at 60 cm was 0.13 logMAR and 0.10
      logMAR in the bilateral group and contralateral group, respectively (difference
      0.04 logMAR), achieving noninferiority. Noninferiority was not attained for CNVA
      at 40 cm; mean values at 3 months for bilateral and contralateral implantation
      were 0.26 logMAR and 0.11 logMAR, respectively (difference 0.15 logMAR).
      Binocular defocus curves suggested similar performance in distance vision between
      the 2 groups. Treatment-emergent ocular adverse events rates were similar between
      the groups. CONCLUSION: Bilateral implantation of the +2.5 D multifocal IOL
      resulted in similar distance as contralateral implantation of the +2.5 D
      multifocal IOL and +3.0 D multifocal IOL for intermediate vision (60 cm), while
      noninferiority was not achieved for near distances (40 cm).

PMID- 27026443
TI  - Evaluation of visual outcomes and patient satisfaction after implantation of a
      diffractive trifocal intraocular lens.
AB  - PURPOSE: To evaluate clinical outcomes after the implantation of a diffractive
      trifocal intraocular lens (IOL). SETTING: Nine European ophthalmology centers.
      DESIGN: Prospective noncomparative interventional multicenter study. METHODS: The
      trifocal diffractive AT LISA tri 839MP IOL was implanted in eyes with bilateral
      cataract. Monocular and binocular visual performance was assessed as was the
      level of perceived photic phenomena, patient satisfaction, and spectacle
      dependence 1 month and 3 months postoperatively. RESULTS: The IOL was implanted
      in 208 eyes of 104 patients. The mean binocular uncorrected distance visual
      acuity improved from 0.44 logMAR +/- 0.30 (SD) to 0.02 +/- 0.10 logMAR and 0.03
      +/- 0.09 logMAR at 1 month and 3 months, respectively (P < .01). The mean
      binocular uncorrected intermediate visual acuity (80 cm) improved from 0.51 +/-
      0.30 logMAR to 0.09 +/- 0.13 logMAR and 0.10 +/- 0.15 logMAR at 1 month and 3
      months, respectively (P < .01). The mean binocular uncorrected near visual acuity
      improved from 0.67 +/- 0.31 logMAR to 0.16 +/- 0.14 logMAR and 0.15 +/- 0.14
      logMAR, respectively (P < .01). Among the more frequently perceived photic
      phenomena were halos; however, approximately 75% of patients were not bothered by
      them. More than 90% of patients were satisfied with the outcome. Spectacle
      independence at all distances was higher than 90%. CONCLUSION: This IOL provided
      excellent visual outcomes and high refractive predictability at all distances,
      including intermediate, leading to high levels of patient satisfaction and
      spectacle independence. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 27026444
TI  - Small-incision 4-point scleral suture fixation of a foldable hydrophilic acrylic
      intraocular lens in the absence of capsule support.
AB  - PURPOSE: To determine the visual outcomes and complications of a new small
      incision technique for 4-point fixation of a hydrophilic acrylic posterior
      chamber intraocular lens (IOL) in the absence of capsule support. SETTING: Three
      North American tertiary referral centers and a private practice. DESIGN:
      Retrospective case series. METHODS: Secondary IOL placement was performed from
      2011 to 2014. Indications for surgery, clinical results, and complications were
      analyzed. Primary outcomes included postoperative corrected distance visual
      acuity (CDVA) and surgical complications. RESULTS: Charts of 35 patients (37
      eyes) were reviewed. The mean age at surgery was 56 years, and the mean follow-up
      was 6 months (range 3 to 24 months). Clinical indications included a dislocated
      IOL (30%), ocular trauma (19%), crystalline lens subluxation (19%), uveitis
      glaucoma-hyphema syndrome (5%), post-complicated cataract (8%), congenital
      cataract (8%), and decompensated cornea (3%). The mean CDVA improved from 20/80
      preoperatively to 20/40 postoperatively (P < .01). Thirty-six eyes (97%) had an
      improved or unchanged CDVA, and 1 eye (3%) had a reduced CDVA because of
      worsening glaucoma. Postoperative complications included ocular hypertension
      (24%), iritis (5%), wound leakage (3%), transient corneal edema (3%), glaucoma
      requiring a tube shunt (3%), and IOL dislocation (3%). CONCLUSION: Small-incision
      4-point scleral fixation of the Akreos AO60 hydrophilic acrylic IOL in the
      absence of capsule support appears to be a safe and effective technique for
      secondary IOL placement. FINANCIAL DISCLOSURES: Drs. Berdahl and Ayres are
      consultants to Bausch & Lomb, Inc. Drs. Ayres and Fram have received speaker fees
      from Bausch & Lomb. Dr. Terveen does not have a financial or proprietary interest
      in any material or methods mentioned.

PMID- 27026445
TI  - Effect of posterior corneal astigmatism on power calculation and alignment of
      toric intraocular lenses: Comparison of methodologies.
AB  - PURPOSE: To compare the accuracy of different methods that consider posterior
      corneal curvature in toric intraocular lens (IOL) calculations. SETTING: Ein-Tal
      Eye Center, Tel-Aviv, Israel. DESIGN: Retrospective comparative case series.
      METHODS: Consecutive cases of toric IOL implantation and preoperative
      measurements by optical biometry with optical low-coherence reflectometry (OLCR)
      (Lenstar LS 900) and a Scheimpflug camera (Pentacam) were retrospectively
      reviewed. Five methods of toric IOL calculation were compared as follows: (1)
      anterior corneal astigmatism using OLCR, (2) application of the Baylor nomogram,
      (3) posterior tomography combined with anterior corneal measurements using vector
      summation, (4) the Scheimpflug camera's true net power, and (5) total corneal
      refractive power. Toric IOL astigmatic power and axis, aiming for the lowest
      residual astigmatism, were selected according to these methods. Simulated
      residual refraction was calculated for each method based on manifest refraction
      and measured IOL alignment more than 3 weeks after surgery. RESULTS: The study
      included 115 eyes of 92 patients. The median simulated residual astigmatism was
      lower when based on vector summation of anterior and posterior astigmatisms than
      with calculations based on anterior corneal measurements only, application of the
      Baylor nomogram, true net power, and total corneal refractive power readings
      (0.49 diopters [D] versus 0.70 D, 0.60 D, 0.64 D, and 0.76 D, respectively) (P <
      .001). CONCLUSIONS: Residual astigmatism after toric IOL implantation can be
      reduced by appropriate consideration of the posterior corneal astigmatism. Using
      methods that take into account the effect of the posterior cornea in toric IOL
      calculations is suggested. FINANCIAL DISCLOSURES: Drs. Assia and Kleinmann are
      consultants to Hanita Lenses, Israel. Dr. Abulafia received a speaker's fee from
      Haag-Streit AG. No other author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 27026446
TI  - Intraocular lens calculation adjustment after laser refractive surgery using
      Scheimpflug imaging.
AB  - PURPOSE: To test a new method of intraocular lens (IOL) calculation after corneal
      refractive surgery using Scheimpflug imaging (Pentacam HR) and partial coherence
      interferometry (PCI) (IOLMaster) that does not require historical data; that is,
      the Schuster/Schanzlin-Thomas-Purcell (SToP) IOL calculator. SETTING: Shiley Eye
      Center, San Diego, California, and Walter Reed National Military Medical Center,
      Bethesda, Maryland, USA. DESIGN: Retrospective data analysis and validation
      study. METHODS: Data were retrospectively collected from patient charts including
      data from Scheimpflug imaging and refractive history. Target refraction was
      calculated using PCI and the Holladay 1 and SRK/T formulas. Regression analysis
      was performed to explain the deviation of the target refraction, taking into
      account the following influencing factors: ratio of posterior-to-anterior corneal
      radius, axial length (AL), and anterior corneal radius. RESULTS: The regression
      analysis study included 61 eyes (39 patients) that had laser in situ
      keratomileusis (57 eyes) or photorefractive keratectomy (4 eyes) and subsequent
      cataract. Two factors were found that explained the deviation of the target
      refraction using the Holladay 1 formula; that is, the ratio of the corneal radii
      and the AL and the ratio of corneal radii for the SRK/T formula. A new IOL
      adjustment calculator was derived and validated at a second center using 14 eyes
      (10 patients). CONCLUSIONS: The error in IOL calculation for normal eyes after
      laser refractive treatment was related to the ratio of posterior-to-anterior
      corneal radius. A formula requiring Scheimpflug data and suggested IOL power only
      yielded an improved postoperative result for patients with previous corneal laser
      refractive surgery having cataract surgery. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 27026447
TI  - Elevated TGF-beta2 level in aqueous humor of cataract patients with high myopia:
      Potential risk factor for capsule contraction syndrome.
AB  - PURPOSE: To evaluate the level of transforming growth factor-beta2 (TGF-beta2) in
      the aqueous humor of highly myopic cataract patients and its correlation with
      capsule contraction syndrome. SETTING: Eye and ENT Hospital of Fudan University,
      Shanghai, China. DESIGN: Prospective comparative case series. METHODS: The highly
      myopic cataract patients were divided into the following 2 groups according to
      the Lens Opacity Classification System III: nuclear color (NC) 2 to 3 and NC 5 to
      6. Aqueous humor TGF-beta2 concentrations were assayed in the highly myopic
      cataract and age-related cataract groups. The TGF-beta2, TGF-betaRII (the type II
      receptor for TGF-beta2), and alpha-smooth muscle actin (alpha-SMA) expressions in
      lens epithelial cells (LECs) were detected by real-time polymerase chain reaction
      and immunofluorescent staining. RESULTS: The study comprised 40 highly myopic
      cataract patients (40 eyes) and 20 patients (20 eyes) with age-related cataract
      as the control group. Compared with the control group, the highly myopic cataract
      group had significantly higher TGF-beta2 concentration in the aqueous humor and
      increased TGF-betaRII expression in LECs, especially in NC 5 to 6 cases.
      Expression of alpha-SMA was barely detectable in both groups. CONCLUSION: In
      highly myopic cataract patients, especially those with dark nuclei, elevated
      aqueous humor TGF-beta2 levels and the upregulated TGF-betaRII expression in LECs
      might contribute to the pathogenesis of capsule contraction syndrome through
      transdifferentiation of LECs into myofibroblasts. FINANCIAL DISCLOSURE: None of
      the authors has a financial or proprietary interest in any material or method
      mentioned.

PMID- 27026448
TI  - Practice patterns of cataract surgeons at academic medical centers for the
      management of inadequate capsule support for intracapsular or sulcus intraocular
      lens placement during cataract surgery.
AB  - PURPOSE: To determine practice patterns with regard to intraocular lens (IOL)
      placement during cataract surgery when there is inadequate capsule support for
      intracapsular or sulcus IOL placement. SETTING: Pennsylvania State College of
      Medicine, Hershey, Pennsylvania, USA. DESIGN: Cross-sectional study of anonymous
      survey results. METHODS: An online survey was e-mailed to the coordinators of all
      Accreditation Council for Graduate Medical Education-accredited ophthalmology
      residency programs with a request to forward to all faculty who perform cataract
      surgery. RESULTS: Sixty-seven (57.2%) of 117 confirmed survey recipients
      participated. Thirty-six (62.1%) said they felt comfortable placing scleral
      fixated posterior chamber IOLs (PC IOLs) independently. Faced with inadequate
      capsule support, 58.6% would place a primary anterior chamber IOL (AC IOL), 29.3%
      would place a primary scleral-fixated PC IOL, and 5.3% would leave the patient
      aphakic for secondary scleral-fixated PC IOL placement. Surgeons not comfortable
      placing scleral-fixated PC IOLs were most likely to choose primary AC IOLs
      (77.3%). Surgeons comfortable placing scleral-fixated PC IOLs were more evenly
      divided between primary AC IOLs (47.2%) and scleral-fixated PC IOLs (41.7%).
      Among surgeons who favored primary scleral-fixated PC IOLs, 63.7% cited a
      decreased risk for long-term complications as their reason for IOL choice; 50.0%
      of surgeons who favored primary AC IOLs cited avoidance of a second surgery.
      CONCLUSIONS: In general, primary AC IOL placement was preferred in the setting of
      inadequate capsule support, although less so among surgeons who were comfortable
      placing scleral-fixated PC IOLs. Lack of comfort with scleral-fixated PC IOL
      placement suggests a potential unmet training need in residency and fellowship
      programs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
      in any material or method mentioned.

PMID- 27026449
TI  - Suction loss during femtosecond laser-assisted small-incision lenticule
      extraction: Incidence and analysis of risk factors.
AB  - PURPOSE: To determine the incidence of and analyze risk factors for suction loss
      during femtosecond laser-assisted small incision lenticule extraction in the
      management of myopia or myopic astigmatism. SETTING: Roayah Vision Correction
      Center, Alexandria, Egypt. DESIGN: Retrospective comparative case-control study.
      METHODS: All eyes that had femtosecond laser-assisted small-incision lenticule
      extraction for the correction of myopia and myopic astigmatism performed between
      August 2010 and April 2014 were included. Eyes that developed suction loss were
      identified. Their characteristics, including demographic data (age and sex), eye
      laterality, manifest refraction, flat keratometry (K) reading, steep K reading, K
      astigmatism, optical zone, central corneal thickness, and corneal cap diameter
      and thickness, were compared with those in randomly selected control eyes to
      determine the risk factors for developing suction loss. RESULTS: Of the 3376 eyes
      that had femtosecond laser-assisted small-incision lenticule extraction during
      the study, 70 (2.1%) developed loss of suction. The incidence decreased with
      surgical experience (5.06% in 2010, 3.59% in 2011, 3.41% in 2012, 2.32% in 2013,
      and 1.84% in 2014), suggesting a learning curve. A multivariate logistic
      regression model showed that eyes with a larger cap diameter were significantly
      more likely to develop suction loss (P = .023; odds ratio, 9.60). CONCLUSIONS:
      Surgical experience significantly decreased the risk for suction loss during
      femtosecond laser-assisted small incision lenticule extraction for the correction
      of myopia or myopic astigmatism but did not eliminate it. A larger cap diameter
      significantly increased the risk for developing the suction loss. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 27026450
TI  - Predictors of femtosecond laser intrastromal astigmatic keratotomy efficacy for
      astigmatism management in cataract surgery.
AB  - PURPOSE: To evaluate the factors associated with the efficacy of femtosecond
      laser intrastromal astigmatic keratotomy (AK). SETTING: Moorfields Eye Hospital,
      London, United Kingdom. DESIGN: Prospective case series. METHODS: Eyes having
      intrastromal AK for corneal cylinder correction were analyzed. Preoperative
      biometric parameters included axial length, anterior chamber depth, central
      corneal thickness, and Ocular Response Analyzer corneal hysteresis (CH) and
      corneal resistance factor (CRF). Preoperative and 1-month postoperative corneal
      keratometry was measured using the Topcon KR8100PA topographer-autorefractor.
      Astigmatic analyses were performed using the Alpins method. RESULTS: The study
      analyzed 319 eyes of 213 patients with a mean target induced astigmatism of 1.24
      diopters (D) +/- 0.44 (SD), mean surgically induced astigmatism (SIA) of 0.71 +/-
      0.43 D, and mean difference vector of 0.79 +/- 0.41 D. Two multiple regression
      models were constructed for SIA prediction. Model 1, based on previous manual
      limbal relaxing incision parameters, confirmed age and astigmatism meridian
      (with/against the rule and oblique) to be associated with SIA in addition to AK
      arc length, AK start depth, and preoperative corneal cylinder magnitude. Model 2,
      additionally considering other parameters, found only lower CH (-0.06 DC per unit
      CH), a higher CRF (0.04 D per unit CRF), and the astigmatism meridian to be
      independent predictors of greater SIA (after adjusting for intrastromal AK arc
      length, start depth, and preoperative corneal cylinder). With-the-rule
      astigmatism was associated with a 0.13 D higher SIA than against-the-rule
      astigmatism, holding all other variables constant. CONCLUSION: Corneal
      biomechanical parameters and astigmatism meridian were independent predictors of
      femtosecond laser intrastromal AK efficacy even after adjusting for AK arc
      length, AK start depth, and preoperative corneal cylinder. FINANCIAL DISCLOSURE:
      Dr. Stevens is a previous consultant to Optimedica, Inc. which is now part of
      Abbott Medical Optics, Inc. Drs. Stevens and Day have no financial or proprietary
      interest in any material or method mentioned.

PMID- 27026451
TI  - Eighteen-year follow-up of hyperopic photorefractive keratectomy.
AB  - PURPOSE: To investigate the long-term efficacy of hyperopic photorefractive
      keratectomy (PRK). SETTING: University Hospital, London, United Kingdom. DESIGN:
      Prospective case series. METHODS: Patients with a follow-up of 18 years +/- 0.7
      (SD) attended for examination. All had spherical corrections with a 6.5 mm
      optical zone and 1.5 mm blend zone. RESULTS: Twenty-five patients (45 eyes) were
      included. The mean preoperative spherical equivalent (SE) refractive error was
      +4.11 +/- 1.8 diopters (D) (range +1.125 to +7.25 D). Between 1 year and 18
      years, in eyes that had no cataract surgery (n = 34), there was a +1.14 +/- 1.48
      D increase in the mean SE (P < .0002). The increase between 7.5 years and 18.0
      years did not reach clinical significance (P = .1). Uncorrected distance visual
      acuity improved at 18 years (P < .02). Corrected distance visual acuity (CDVA)
      was reduced (P < .001). The efficacy index was 0.47, and the safety index was
      0.83. Six eyes (18%) lost 2 lines of CDVA, of which 4 eyes had preexisting
      cataract. Keratometry remained stable between 1 year and 18 years (P = .2). Forty
      percent still had traces of peripheral haze, and 4 (9%) had Salzmann-like
      changes. Eleven eyes (24%) had cataract surgery and 4 (9%) had laser iridotomy.
      There was no evidence of ectasia. CONCLUSIONS: Hyperopic PRK showed an increase
      in hyperopic SE between 1.0 year and 7.5 years but was generally stable
      thereafter. The efficacy was limited. Peripheral haze was evident in 40% of cases
      with Salzmann-like changes in some. Ocular comorbidity in relationship to
      cataract was common and reduced CDVA. FINANCIAL DISCLOSURE: Dr. Marshall was a
      consultant to Summit Technology, Inc. No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 27026452
TI  - Quality control outcomes analysis of small-incision lenticule extraction for
      myopia by a novice surgeon at the first refractive surgery unit in Nepal during
      the first 2 years of operation.
AB  - PURPOSE: To evaluate the outcomes of small-incision lenticule extraction for
      myopia using the Visumax femtosecond laser at the first refractive surgery unit
      in Nepal during the first 30 months of operation. SETTING: Tilganga Institute of
      Ophthalmology, Kathmandu, Nepal. DESIGN: Retrospective noncomparative case
      series. METHODS: Consecutive myopic small-incision lenticule extraction
      procedures by a fellowship-trained surgeon were evaluated. Inclusion criteria
      were a preoperative spherical equivalent (SE) refraction up to -10.00 diopters
      (D) and corrected distance visual acuity (CDVA) of 20/20 or better. Outcomes
      analysis using the Standard Graphs for Reporting Refractive Surgery was performed
      over a 3-month follow-up. RESULTS: Three-month data were available for 1396 eyes.
      The mean attempted SE was -5.78 D +/- 1.81 (SD) (range -0.96 to -10.00 D) and the
      mean cylinder, 0.79 +/- 0.69 D (range 0.00 to 5.25 D). Postoperatively, the mean
      SE relative to target was -0.28 +/- 0.29 D (range -1.31 to +1.50 D) and was
      within +/- 0.50 D in 80% of eyes and +/- 1.00 D in 99% of eyes. The uncorrected
      distance visual acuity was 20/20 or better in 95% of eyes and 20/25 or better in
      99% of eyes. One line of CDVA was lost in 2% of eyes; no eye lost 2 or more
      lines. There was a small improvement in contrast sensitivity (P < .01).
      CONCLUSIONS: The outcomes of myopic small-incision lenticule extraction up to 
      10.00 D performed at the first refractive surgery unit in Nepal by a fellowship
      trained surgeon with no corneal refractive surgery experience were as safe and
      effective as outcomes in previous studies. FINANCIAL DISCLOSURE: Dr. Reinstein is
      a consultant to Carl Zeiss Meditec AG and has a proprietary interest in the
      Artemis technology (Arcscan, Inc.) through patents administered by the Center for
      Technology Licensing at Cornell University, Ithaca, New York, USA. Drs. Pradhan
      and Carp have travel expenses to conferences paid by Carl Zeiss Meditec AG. No
      other author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 27026453
TI  - Accuracy of machine learning classifiers using bilateral data from a Scheimpflug
      camera for identifying eyes with preclinical signs of keratoconus.
AB  - PURPOSE: To describe the topographic and tomographic characteristics of normal
      fellow eyes of unilateral keratoconus cases and to evaluate the accuracy of
      machine learning classifiers in discriminating healthy corneas from the normal
      fellow corneas. SETTING: Department of Ophthalmology, Semmelweis University,
      Budapest, Hungary. DESIGN: Retrospective case-control study. METHODS: Patients
      with bilateral keratoconus (keratoconus group), clinically and according to the
      keratoconus indices of the Pentacam HR Scheimpflug camera; normal fellow eyes of
      patients with unilateral keratoconus (fellow-eye group); and eyes of refractive
      surgery candidates (control group) were compared. Tomographic data, topographic
      data, and keratoconus indices were measured in both eyes using the Scheimpflug
      camera. Receiver operating characteristic (ROC) analysis was used to assess the
      performance of automated classifiers trained on bilateral data as well as
      individual parameters to discriminate fellow eyes of patients with keratoconus
      from control eyes. RESULTS: Keratometry, elevation, and keratoconus indices
      values were significantly higher and pachymetry values were significantly lower
      in keratoconus eyes than in fellow eyes of unilateral keratoconus cases (P <
      .001). These fellow eyes had significantly higher keratometry, elevation, and
      keratoconus index values and significantly lower pachymetry values than control
      eyes (P < .001). Automated classifiers trained on bilateral data of index of
      height decentration had higher accuracy than the unilateral single parameter in
      discriminating fellow eyes of patients with keratoconus from control eyes (area
      under ROC 0.96 versus 0.88). CONCLUSION: Automatic classifiers trained on
      bilateral data were better than single parameters in discriminating fellow eyes
      of patients with unilateral keratoconus with preclinical signs of keratoconus
      from normal eyes. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 27026455
TI  - Lens epithelial cell growth on the anterior optic of 2 hydrophobic intraocular
      lens models.
AB  - PURPOSE: To evaluate lens epithelial cell (LEC) proliferation on the anterior
      optic of 2 types of hydrophobic intraocular lenses (IOLs). SETTING: Harlan
      Biotech Israel and Kaplan Medical Center, Rehovot, Israel. DESIGN: Experimental
      study. METHODS: Ten New Zealand white rabbits had crystalline lens removal and
      implantation of an Acrysof IOL in 1 eye (Group 1) and a Tecnis IOL in the fellow
      eye (Group 2). A weekly biomicroscopy examination was performed during the 2-week
      study duration, after which the rabbits were humanely killed. The eyes were
      enucleated, and the complexes containing the IOL and the capsular bag were
      evaluated for the presence of LECs and large cells (macrophages and giant cells)
      on the IOL anterior optic and for proteinaceous matrix deposits along the
      capsulorhexis margin. RESULTS: Lens epithelial cell were detected on all of the
      IOLs in Group 1 and on none in Group 2 (P < .001). Areas of proteinaceous matrix
      deposits adjacent to the edge of the capsulorhexis were detected on 8 IOLs in
      Group 1 and on none in Group 2 (P < .001). Large cells were identified on all
      IOLs in Group 1 and on 9 IOLs in Group 2 (P = 1.0). No difference in the general
      inflammation markers was found between the 2 IOL types (P = .234). CONCLUSIONS:
      Lens epithelial cell with corresponding proteinaceous matrix deposits were
      significantly more abundant on the IOLs in Group 1 than on the IOLs in Group 2.
      There was no difference in the presence of large cells or in general inflammation
      markers between the 2 IOL types. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 27026454
TI  - Subclinical keratoconus detection by pattern analysis of corneal and epithelial
      thickness maps with optical coherence tomography.
AB  - PURPOSE: To screen for subclinical keratoconus by analyzing corneal, epithelial,
      and stromal thickness map patterns with Fourier-domain optical coherence
      tomography (OCT). SETTING: Four centers in the United States. DESIGN: Cross
      sectional observational study. METHODS: Eyes of normal subjects, subclinical
      keratoconus eyes, and the topographically normal eye of a unilateral keratoconus
      patient were studied. Corneas were scanned using a 26,000 Hz Fourier-domain OCT
      system (RTVue). Normal subjects were divided into training and evaluation groups.
      Corneal, epithelial, and stromal thickness maps and derived diagnostic indices,
      including pattern standard deviation (PSD) variables and pachymetric map-based
      keratoconus risk scores, were calculated from the OCT data. Area under the
      receiver operating characteristic curve (AUC) analysis was used to evaluate the
      diagnostic accuracy of the indices. RESULTS: The study comprised 150 eyes of 83
      normal subjects, 50 subclinical keratoconus eyes of 32 patients, and 1
      topographically normal eye of a unilateral keratoconus patient. Subclinical
      keratoconus was characterized by inferotemporal thinning of the cornea,
      epithelium, and stroma. The PSD values for corneal (P < .001), epithelial (P <
      .001), and stromal (P = .049) thickness maps were all significantly higher in
      subclinical keratoconic eyes than in the normal group. The diagnostic accuracy
      was significantly higher for PSD variables (pachymetric PSD, AUC = 0.941;
      epithelial PSD, AUC = 0.985; stromal PSD, AUC = 0.924) than for the pachymetric
      map-based keratoconus risk score (AUC = 0.735). CONCLUSIONS: High-resolution
      Fourier-domain OCT could map corneal, epithelial, and stromal thicknesses.
      Corneal and sublayer thickness changes in subclinical keratoconus could be
      detected with high accuracy using PSD variables. These new diagnostic variables
      might be useful in the detection of early keratoconus. FINANCIAL DISCLOSURES:
      Oregon Health and Science University (OHSU) and Drs. Li, Tan, and Huang have a
      significant financial interest in Optovue, Inc. These potential conflicts have
      been reviewed and managed by OHSU. Dr. Brass receives research grants from
      Optovue, Inc. Drs. Chamberlain and Weiss have no financial or proprietary
      interest in any material or method mentioned.

PMID- 27026457
TI  - Efficacy and safety of multifocal intraocular lenses following cataract and
      refractive lens exchange: Metaanalysis of peer-reviewed publications.
AB  - We performed a metaanaysis of peer-reviewed studies involving implantation of a
      multifocal intraocular lens (IOL) in presbyopic patients with cataract or having
      refractive lens exchange (RLE). Previous reviews have considered the use of
      multifocal IOLs after cataract surgery but not after RLE, whereas greater insight
      might be gained from examining the full range of studies. Selected studies were
      examined to collate outcomes with monocular and binocular uncorrected distance,
      intermediate, and near visual acuity; spectacle independence; contrast
      sensitivity; visual symptoms; adverse events; and patient satisfaction. In 8797
      eyes, the mean postoperative monocular uncorrected distance visual acuity (UDVA)
      was 0.05 logMAR +/- 0.006 (SD) (Snellen equivalent 20/20(-3)). In 6334 patients,
      the mean binocular UDVA was 0.04 +/- 0.00 logMAR (Snellen equivalent 20/20(-2)),
      with a mean spectacle independence of 80.1%. Monocular mean UDVA did not differ
      significantly between those who had a cataract procedure and those who had an RLE
      procedure. Neural adaptation to multifocality may vary among patients. FINANCIAL
      DISCLOSURE: Dr. Alio is a clinical research investigator for Hanita Lenses, Carl
      Zeiss Meditec AG, Topcon Medical Systems, Inc., Oculentis GmbH, and Akkolens
      International BV. Dr. Dell is a consultant to Bausch & Lomb and Abbott Medical
      Optics, Inc. Dr. Slade is a consultant to Alcon Surgical, Inc., Carl Zeiss
      Meditec AG, and Bausch & Lomb. None of the authors has a financial or proprietary
      interest in any material or method mentioned.

PMID- 27026456
TI  - Early wound healing of laser in situ keratomileusis-like flaps after treatment
      with human corneal stromal stem cells.
AB  - PURPOSE: To use a well-established organ culture model to investigate the effects
      of corneal stromal stem cells on the optical and biomechanical properties of
      corneal wounds after laser in situ keratomileusis (LASIK)-like flap creation.
      SETTING: School of Optometry and Vision Sciences, Cardiff University, Cardiff,
      Wales, United Kingdom. DESIGN: Experimental study. METHODS: The LASIK-like flaps
      were produced in sheep corneas. The flap beds were treated with corneal stromal
      stem cells and were then replaced and allowed to heal for different periods of up
      to 3 weeks in organ culture. The optical transmission of the cornea, the force
      required to detach the flap, and the presence of myofibroblasts near the flap bed
      were measured. RESULTS: Corneal stromal stem cell-treated flap beds were
      statistically significantly more transparent after 3 weeks in culture than the
      untreated controls. At 3 weeks, the mean force necessary to detach the flap was
      more than twice the force required for the respective control samples.
      Concurrently, there were 44% activated cells immediately below the flap margin of
      the controls compared with 29% in the same region of the corneal stromal stem
      cell-treated flaps. CONCLUSIONS: In this system, the presence of corneal stromal
      stem cells at the wound margin significantly increased the adherence of LASIK
      like flaps while maintaining corneal transparency. It is postulated that this is
      achieved by the deposition of extracellular connective tissue similar to that
      found in the normal cornea and by the paucity of activated keratocytes
      (myofibroblasts), which are known to scatter a significant amount of the incident
      light. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in
      any material or method mentioned.

PMID- 27026458
TI  - Bilateral rupture of the posterior capsule and intraocular lens dislocation from
      excessive eye rubbing.
AB  - We report an unusual case of a 36-year-old woman with severe atopic eczema who
      developed sudden-onset reduction of vision in the right eye following excessive
      eye rubbing 9 years after cataract surgery. Examination identified posterior
      capsule rupture with dislocation of the intraocular lens (IOL) posteriorly into
      the vitreous cavity in the right eye and posterior capsule rupture with mild
      dislocation of the IOL in the bag in the left eye. To our knowledge, this is the
      first reported case of simultaneous bilateral posterior capsule rupture following
      uneventful surgery and secondary to eye rubbing. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 27026459
TI  - Structure of the entire capsular bag containing an endocapsular equator ring and
      intraocular lens.
AB  - We report in vivo observation of a capsular bag containing an endocapsular
      equator ring and intraocular lens that was explanted 5 years after the initial
      surgery. The capsule equator remained completely circular. The inside of the
      capsular bag retained the open space, and the endocapsular equator ring blocked
      proliferative tissue under the anterior capsule at the equator and prevented
      posterior capsule opacification. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 27026460
TI  - Successful treatment of negative dysphotopsia with in-the-bag intraocular lens
      exchange using a wide ovoid IOL.

PMID- 27026461
TI  - Patient bias toward lasers: Hidden vulnerability in the widespread adoption of
      femtosecond laser-assisted cataract surgery.

PMID- 27026462
TI  - February consultation #2.

PMID- 27026463
TI  - Subluxated multifocal intraocular lens-capsular bag-capsular tension ring
      complex. February consultation #1.

PMID- 27026464
TI  - February consultation #3.

PMID- 27026465
TI  - February consultation #4.

PMID- 27026466
TI  - February consultation #5.

PMID- 27026467
TI  - February consultation #6.

PMID- 27026468
TI  - February consultation #7.

PMID- 27026469
TI  - February consultation #8.

PMID- 27026470
TI  - February consultation #9.

PMID- 27026471
TI  - Reply.

PMID- 27026472
TI  - Rationale for choosing crossed monovision.

PMID- 27026474
TI  - Erratum.

PMID- 27026473
TI  - Surgically induced astigmatism is characterized by optical vectors, not by
      ratios.

PMID- 27026475
TI  - Pregnancy-associated homicide and suicide in 37 US states with enhanced pregnancy
      surveillance.
AB  - BACKGROUND: Pregnant and postpartum women may be at increased risk of violent
      death including homicide and suicide relative to nonpregnant women, but US
      national data have not been reported since the implementation of enhanced
      mortality surveillance. OBJECTIVE: The objective of the study was to estimate
      homicide and suicide ratios among women who are pregnant or postpartum and to
      compare their risk of violent death with nonpregnant/nonpostpartum women. STUDY
      DESIGN: Death certificates (n = 465,097) from US states with enhanced pregnancy
      mortality surveillance from 2005 through 2010 were used to compare mortality
      among 4 groups of women aged 10-54 years: pregnant, early postpartum (pregnant
      within 42 days of death), late postpartum (pregnant within 43 days to 1 year of
      death), and nonpregnant/nonpostpartum. We estimated pregnancy-associated
      mortality ratios and compared with nonpregnant/nonpostpartum mortality ratios to
      identify differences in risk after adjusting for potential levels of pregnancy
      misclassification as reported in the literature. RESULTS: Pregnancy-associated
      homicide victims were most frequently young, black, and undereducated, whereas
      pregnancy-associated suicide occurred most frequently among older white women.
      After adjustments, pregnancy-associated homicide risk ranged from 2.2 to 6.2 per
      100,000 live births, depending on the degree of misclassification estimated,
      compared with 2.5-2.6 per 100,000 nonpregnant/nonpostpartum women aged 10-54
      years. Pregnancy-associated suicide risk ranged from 1.6-4.5 per 100,000 live
      births after adjustments compared with 5.3-5.5 per 100,000 women aged 10-54 years
      among nonpregnant/nonpostpartum women. Assuming the most conservative published
      estimate of misclassification, the risk of homicide among pregnant/postpartum
      women was 1.84 times that of nonpregnant/nonpostpartum women (95% confidence
      interval, 1.71-1.98), whereas risk of suicide was decreased (relative risk, 0.62,
      95% confidence interval, 0.57-0.68). CONCLUSION: Pregnancy and postpartum appear
      to be times of increased risk for homicide and decreased risk for suicide among
      women in the United States.

PMID- 27026476
TI  - Gastroschisis: epidemiology and mode of delivery, 2005-2013.
AB  - BACKGROUND: Gastroschisis is a severe congenital anomaly the etiology of which is
      unknown. Research evidence supports attempted vaginal delivery for pregnancies
      complicated by gastroschisis in the absence of obstetric indications for cesarean
      delivery. OBJECTIVE: The objectives of the study evaluating pregnancies
      complicated by gastroschisis were to determine the proportion of women undergoing
      planned cesarean vs attempted vaginal delivery and to provide up-to-date
      epidemiology on the risk factors associated with this anomaly. STUDY DESIGN: This
      population-based study of US natality records from 2005 through 2013 evaluated
      pregnancies complicated by gastroschisis. Women were classified based on whether
      they attempted vaginal delivery or underwent a planned cesarean (n = 24,836,777).
      Obstetrical, medical, and demographic characteristics were evaluated.
      Multivariable log-linear regression models were developed to determine the
      factors associated with the mode of delivery. Factors associated with the
      occurrence of the anomaly were also evaluated in log-linear models. RESULTS: Of
      5985 pregnancies with gastroschisis, 63.5% (n = 3800) attempted vaginal delivery
      and 36.5% (n = 2185) underwent a planned cesarean delivery. The rate of attempted
      vaginal delivery increased from 59.7% in 2005 to 68.8% in 2013. Earlier
      gestational age and Hispanic ethnicity were associated with lower rates of
      attempted vaginal delivery. Factors associated with the occurrence of
      gastroschisis included young age, smoking, high educational attainment, and being
      married. Protective factors included chronic hypertension, black race, and
      obesity. The incidence of gastroschisis was 3.1 per 10,000 pregnancies and did
      not increase during the study period. CONCLUSION: Attempted vaginal delivery is
      becoming increasingly prevalent for women with a pregnancy complicated by
      gastroschisis. Recommendations from the research literature findings may be
      diffusing into clinical practice. A significant proportion of women with this
      anomaly still deliver by planned cesarean, suggesting further reduction of
      surgical delivery for this anomaly is possible.

PMID- 27026477
TI  - Reduced levels of genital tract immune biomarkers in postmenopausal women:
      implications for HIV acquisition.
AB  - BACKGROUND: Rates of HIV infections are increasing in older adults. Although it
      is known that the HIV/AIDS epidemics affects women disproportionately, little is
      known regarding immune functions in the genital tract of postmenopausal women, as
      relevant to HIV susceptibility. OBJECTIVE: The objective of the study was to
      compare levels of female reproductive tract immune mediators that are important
      for HIV-associated immune responses as well as intrinsic anti-HIV activity in the
      cervical vaginal lavages collected from HIV-negative pre- and postmenopausal
      women. STUDY DESIGN: Cervical vaginal lavage from 20 premenopausal and 20
      postmenopausal women were assayed for interleukin-6, interleukin-8, tumor
      necrosis factor-alpha, secretory leukocyte protease inhibitor, elafin, human beta
      defensin-2, and macrophage inflammatory protein-3alpha using standard enzyme
      linked immunosorbent assays. Anti-HIV activity of cervical-vaginal lavage was
      measured using TZM-bl indicator cells against HIV-1 IIIB and BaL. Whereas each
      postmenopausal woman provided only 1 sample, each premenopausal woman provided 3
      samples, during proliferative, ovulatory, and secretory stages, based on
      menstrual dates. RESULTS: We observed significantly lower levels of tumor
      necrosis factor-alpha, MIP-3alpha, secretory leukocyte protease inhibitor,
      elafin, and human beta-defensin-2 in cervical vaginal lavage from postmenopausal
      women compared with premenopausal women. Inhibition of HIV-1 infection was
      observed for both pre- and postmenopausal women, but cervical vaginal lavage from
      postmenopausal women showed significantly higher inhibition against HIV-1 BaL
      after adjusting for total protein concentration, genital pH, and reproductive
      tract infections. No change in mediators or HIV inhibition was observed through
      the stages of menstrual cycle. In addition, we observed that postmenopausal women
      with reproductive tract infections had significantly higher levels of tumor
      necrosis factor-alpha and significantly lower levels of interleukin-8, which were
      not observed in premenopausal women. CONCLUSION: Our findings suggest that female
      reproductive tract immune microenvironment is distinct in HIV-negative
      postmenopausal women. Further studies are needed to assess the risk of HIV
      acquisition/transmission in this population.

PMID- 27026478
TI  - Multifocal intraductal papillary mucinous neoplasm of the pancreas from mild
      dysplasia to invasive carcinoma A case report.
AB  - Intraductal papillary mucinous neoplasm (IPMN) is defined as an intraductal mucin
      producing neoplasm of the pancreatic ducts. IPMNs may be multifocal, have
      malignant potential and exhibit a broad histological spectrum ranging from
      adenoma to invasive carcinoma. The "hyperplasia-dysplasia-carcinoma sequence" in
      the evolution of IPMNs is considered very similar to the "adenoma-carcinoma
      sequence" of colorectal tumours. Patients with multifocal IPMN are potential
      candidates to total pancreatectomy, which still carries significant perioperative
      risks, especially in the elderly. In selected cases a reasonable alternative to
      total pancreatectomy is represented by the resection of the dominant tumour
      leaving deliberately in place the smaller, low-risk tumours. In this context,
      intraoperative ultrasonography (IOUS) can be useful to define the extent of IPMNs
      and to plan the surgical strategy. We report the case of a 84-year-old female
      with multiple IPMNs showing different stages of neoplastic progression up to
      invasive carcinoma. The patient underwent IOUS-guided distal
      splenopancreatectomy, while the small multiple branchduct type IPMNs of the head
      of the pancreas were considered at very low risk of neoplastic progression and
      were deliberately left in place. The patient is alive without recurrence 96
      months after surgery and without evidence of progression of the branch-duct type
      IPMNs of the head of the pancreas. IOUS-guided pancreatectomy should be
      considered in selected elderly patients affected by multifocal IPMN evolved to
      invasive carcinoma without evidence of distant metastases. KEY WORDS: Intraductal
      papillary mucinous neoplasm, Intraoperative ultrasonography, Pancreatectomy.

PMID- 27026479
TI  - Crystallization kinetics of the phase change material GeSb6Te measured with
      dynamic transmission electron microscopy.
AB  - GeSb6Te is a chalcogenide-based phase change material that has shown great
      ptoential for use in solid-state memory devices. The crystallization kinetics of
      amorphous thin films of GeSb6Te during laser crystallization were followed with
      dynamic transmission electron microscopy, a photo-emission electron microscopy
      technique with nanosecond-scale time resolution. Nine-frame movies of crystal
      growth were taken during laser crystallization. The nucleation rate is observed
      to be very low and the growth rates are very high, up to 10.8 m s(-1) for
      amorphous as-deposited films and significantly higher for an amorphous film
      subject to sub-threshold laser annealing before crystallization. The measured
      growth rates exceed any directly measured growth rate of a phase change material.
      The crystallization is reminiscent of explosive crystallization of elemental
      semiconductors both in the magnitude of the growth rate and in the resulting
      crystalline microstructures. 

PMID- 27026480
TI  - Comparative Connectomics.
AB  - We introduce comparative connectomics, the quantitative study of cross-species
      commonalities and variations in brain network topology that aims to discover
      general principles of network architecture of nervous systems and the
      identification of species-specific features of brain connectivity. By comparing
      connectomes derived from simple to more advanced species, we identify two
      conserved themes of wiring: the tendency to organize network topology into
      communities that serve specialized functionality and the general drive to enable
      high topological integration by means of investment of neural resources in short
      communication paths, hubs, and rich clubs. Within the space of wiring
      possibilities that conform to these common principles, we argue that differences
      in connectome organization between closely related species support adaptations in
      cognition and behavior.

PMID- 27026481
TI  - A New Framework to Explain Sensorimotor Beta Oscillations.
AB  - Oscillatory activity in the beta frequency range from sensorimotor cortices is
      modulated by movement; however, the functional role of this activity remains
      unknown. In a recent study, Tan et al. tested a novel hypothesis that beta power
      reflects estimates of uncertainty in parameters of motor forward models.

PMID- 27026483
TI  - Culturally Competent Palliative and Hospice Care Training for Ethnically Diverse
      Staff in Long-Term Care Facilities.
AB  - Between 2013 and 2030, older adults 65 years and older of racial/ethnic
      populations in the U.S. is projected to increase by 123% in comparison to the
      Whites (Non-Hispanics). To meet this demand, training of ethnically diverse
      health staff in long-term care facilities in palliative and hospice care is
      imperative. The purpose of this study was to evaluate a palliative and hospice
      care training of staff in two nursing homes in Hawaii - (a) to evaluate knowledge
      and confidence over three time periods, and (b) to compare staff and family
      caregiver satisfaction at end of program. The educational frameworks were based
      on cultural and communication theories. Fifty-two ethnically diverse staff, a
      majority being Asian (89%), participated in a 10-week module training and one 4
      hour communication skills workshop. Staff evaluation included knowledge and
      confidence surveys, pre- and post-test knowledge tests, and FAMCARE-2
      satisfaction instrument. There were nine Asian (89%) and Pacific Islander (11%)
      family caregivers who completed the FAMCARE-2 satisfaction instrument. The
      overall staff knowledge and confidence results were promising. The staff rated
      overall satisfaction of palliative care services lower than the family
      caregivers. Implications for future research, practice, and education with
      palliative and hospice care training of ethnically diverse nursing home staff is
      to include patient and family caregiver satisfaction of palliative and hospice
      care services, evaluation of effectiveness of cross-cultural communication
      theories in palliative and hospice care staff training, and support from
      administration for mentorship and development of these services in long term care
      facilities.

PMID- 27026482
TI  - Oral azithromycin given during labour decreases bacterial carriage in the mothers
      and their offspring: a double-blind randomized trial.
AB  - Bacterial sepsis remains a leading cause of death among neonates with
      Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae
      identified as the most common causative pathogens in Africa. Asymptomatic
      bacterial colonization is an intermediate step towards sepsis. We conducted a
      phase III, double-blind, placebo-controlled randomized trial to determine the
      impact of giving one oral dose of azithromycin to Gambian women in labour on the
      nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day
      6 postpartum. Study participants were recruited in a health facility in western
      Gambia. They were followed for 8 weeks and samples were collected during the
      first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who
      delivered 843 babies, including 13 stillbirths. Sixteen babies died during the
      follow-up period. No maternal deaths were observed. No serious adverse events
      related to the intervention were reported. According to the intent-to-treat
      analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in
      the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1%
      prevalence ratio 0.43; 95% CI 0.36-0.52, p <0.001). At the same time-point,
      prevalence of any bacteria in the mother was also lower in the azithromycin group
      (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p
      <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between
      arms lasted for at least 4 weeks. Oral azithromycin given to women in labour
      decreased the carriage of bacteria of interest in mothers and newborns and may
      lower the risk of neonatal sepsis. Trial registrationClinicalTrials.gov
      Identifier NCT01800942. 

PMID- 27026484
TI  - Glial cell derived neurotrophic factor induces spermatogonial stem cell marker
      genes in chicken mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage
      differentiation. Advances in differentiation technology have also resulted in the
      conversion of MSCs to other kinds of stem cells. MSCs are considered as a
      suitable source of cells for biotechnology purposes because they are abundant,
      easily accessible and well characterized cells. Nowadays small molecules are
      introduced as novel and efficient factors to differentiate stem cells. In this
      work, we examined the potential of glial cell derived neurotrophic factor (GDNF)
      for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were
      isolated and characterized from chicken and cultured under treatment with all
      trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression
      analysis of specific genes after 7days of RA treatment, as examined by RT-PCR,
      proved positive for some germ cell markers such as CVH, STRA8, PLZF and some
      genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On
      the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as
      well as other genes which were induced after RA treatment. These data illustrated
      that GDNF is relatively more effective in diverting chicken MSCs towards
      Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent
      to obtain transgenic poultry, nevertheless, exploitability of these cells should
      be verified by more experiments. 

PMID- 27026485
TI  - The current management of cholangiocarcinoma: A comparison of current guidelines.
AB  - Cholangiocarcinoma (CC) accounts for about 3% of all gastrointestinal tumors and
      is the second most common primary liver tumor. Quality guidelines on CC are
      needed to guide hepatobiliary surgeons. Here, current guidelines on CC were
      reviewed to provide useful information and suggestions to help institutes and
      organizations all around the world to draft better guidelines on CC. Literature
      databases were electronically searched to identify guidelines or consensus
      statements regarding CC published from 2002-2016. Nine guidelines were included
      in this review. Comparison of the current guidelines revealed several
      inconsistencies. Signs of conflicting views indicated a lack of high level
      evidence. More studies need to be conducted in areas of contention to help update
      the guidelines. Organizations and medical societies need to be encouraged to use
      standard evaluation measures, to restrict tumors to CC or iCC, pCC, or dCC
      specifically, to give recommendations in accordance with the equipment that is
      available for diagnosis and treatment in different counties, and to use an
      appropriate and consistent structure when establishing and drafting guidelines
      for CC. 

PMID- 27026486
TI  - Curcumin reduces brain-infiltrating T lymphocytes after intracerebral hemorrhage
      in mice.
AB  - T lymphocytes contribute to inflammation, thereby exacerbating neuronal injury
      after cerebral ischemia. An increasing amount of evidence indicates that
      inflammation is a key contributor to intracerebral hemorrhage (ICH)-induced
      secondary brain injury. Curcumin, a low-molecular-weight curry spice that is
      derived from the Curcuma longa plant, suppresses T lymphocyte proliferation and
      migration. Based on these findings, we investigated whether treatment with
      curcumin would reduce the number of cerebral T lymphocytes in mice with
      experimentally induced ICH. We found that a large number of T lymphocytes
      infiltrated the brain at 3days post-ICH. Curcumin significantly improved
      neurological scores and reduced brain edema in mice with ICH, consistent with a
      role in reducing neuroinflammation and neurovascular injury. Using flow
      cytometry, we observed significantly fewer T lymphocytes in brain samples
      obtained from the curcumin-treated group than in samples obtained from the
      vehicle-treated group. Moreover, Western blot analysis and immunostaining
      indicated that treatment with curcumin significantly reduced the expression of a
      vascular cell adhesion molecule-1 (VCAM-1), interferon-gamma (INF-gamma) and
      interleukin-17 (IL-17) in the mouse brain at 72h post-ICH. Our results suggest
      that administering curcumin may alleviate cerebral inflammation resulting from
      ICH, at least in part by reducing the infiltration of T lymphocytes into the
      brain. Therefore, preventing T lymphocytes from infiltrating the brain may become
      a new strategy for treating clinical ICH.

PMID- 27026487
TI  - Neuron-specific enolase levels in drug-naive young adults with major depressive
      disorder.
AB  - The aim of this study is to assess neuron-specific enolase (NSE) levels and
      clinical features in subjects with major depressive disorder (MDD). This is a
      cross-sectional study with drug-naive young adults with MDD (aged 18-29 years).
      Serum levels of NSE were assessed using the electrochemiluminescence method. MDD
      diagnosis, suicidal ideation, and time of disease were assessed using the
      Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating
      Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess
      depressive and anxiety symptoms. No relationship was observed between NSE levels
      and severity of depressive and anxiety symptoms, time of disease, and suicidal
      ideation. These results suggest that NSE serum levels were not associated with
      clinical features of MDD among drug-naive young adults.

PMID- 27026488
TI  - Electroacupuncture relieves neuropathic pain via upregulation of glutamate
      transporters in the spinal cord of rats.
AB  - Glutamate transports (GTs), the only vehicle for removal of glutamate from the
      extracellular fluid, is reported to be related to chronic pain. To investigate
      whether the glutamate/aspartate transporter (GLAST) and glutamate transporter-1
      (GLT-1) participate in electroacupuncture (EA) analgesia, the EA effect was
      observed with paw withdraw threshold in a rat model of spared nerve injury. The
      expression levels of GLAST and GLT-1 were determined with Western Blot and RT
      PCR. The results showed significantly upregulated GLAST and GLT-1, along with the
      relieved pain behaviors after EA treatment. In addition, intrathecal injection of
      GTs inhibitor, l-trans-pyrrolidine-2-4-dicarboxylate, attenuated the EA-induced
      analgesic effect. The experiment demonstrates that EA can increase the GTs of
      neuropathic pain rats, which might be one of the mechanisms underlying its
      effectiveness in the neuropathic pain.

PMID- 27026489
TI  - The association between CYP46A1 rs4900442 polymorphism and the risk of
      Alzheimer's disease: A meta-analysis.
AB  - Polymorphisms in the CYP46A1 rs4900442 have been controversially associated with
      increased risk of developing Alzheimer's disease (AD). Therefore, a meta-analysis
      was performed to assess the possible association between CYP46A1 gene rs4900442
      polymorphism and AD. A comprehensive search was conducted to identify all case
      control or cohort design studies of the associations between CYP46A1 rs4900442
      and AD. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using
      fixed-effects models. Heterogeneity among studies was evaluated using the I(2)
      and funnel plot and Egger's test were used to evaluate publication bias.
      Sensitivity analysis was also performed. Six case-control studies corresponded to
      the inclusion criteria including 1555 AD cases and 1347 controls for the present
      meta-analysis. Our results showed that no significant associations between
      CYP46A1 rs4900442 genetic polymorphism and risk of AD in allele model T vs. C
      (OR=0.947, 95%CI=0.853-1.051), dominant model CC+TC vs. TT (OR=0.878, 95%CI=0.734
      1.049) and recessive model CC vs. TC+TT (OR=0.974, 95%CI=0.826-1.149). Moreover,
      in the subgroup analysis based on location (Chinese and Caucasian), there was
      significant association in Chinese population in allele model T vs. C (OR=0.780,
      95%CI=0.628-0.968), although no obvious associations were found in Caucasian. The
      meta-analysis suggested that CYP46A1 rs4900442 genetic polymorphism was
      associated with increased risk of AD in the Chinese population, but no evidences
      were detected in Caucasian population.

PMID- 27026490
TI  - Decadal predictions of the North Atlantic CO2 uptake.
AB  - As a major CO2 sink, the North Atlantic, especially its subpolar gyre region, is
      essential for the global carbon cycle. Decadal fluctuations of CO2 uptake in the
      North Atlantic subpolar gyre region are associated with the evolution of the
      North Atlantic Oscillation, the Atlantic meridional overturning circulation,
      ocean mixing and sea surface temperature anomalies. While variations in the
      physical state of the ocean can be predicted several years in advance by
      initialization of Earth system models, predictability of CO2 uptake has remained
      unexplored. Here we investigate the predictability of CO2 uptake variations by
      initialization of the MPI-ESM decadal prediction system. We find large multi-year
      variability in oceanic CO2 uptake and demonstrate that its potential predictive
      skill in the western subpolar gyre region is up to 4-7 years. The predictive
      skill is mainly maintained in winter and is attributed to the improved physical
      state of the ocean. 

PMID- 27026491
TI  - In situ electro-polymerization of nitrogen doped carbon dots and their
      application in an electrochemiluminescence biosensor for the detection of
      intracellular lead ions.
AB  - Here, a novel sensitive electrochemiluminescence (ECL) biosensor using N doped
      carbon dots (N-CDs) in situ electro-polymerized onto a glassy carbon electrode
      (GCE) as luminophores, and Pd-Au hexoctahedrons (Pd@Au HOHs) as enhancers, was
      developed for the detection of intracellular lead ions (Pb(2+)). 

PMID- 27026492
TI  - Food waste from Danish households: Generation and composition.
AB  - Sustainable solutions for reducing food waste require a good understanding of
      food waste generation and composition, including avoidable and unavoidable food
      waste. We analysed 12tonnes of residual household waste collected from 1474
      households, without source segregation of organic waste. Food waste was divided
      into six fractions according to avoidability, suitability for home-composting and
      whether or not it was cooked, prepared or had been served within the household.
      The results showed that the residual household waste generation rate was 434+/
      18kg per household per year, of which 183+/-10kg per year was food waste.
      Unavoidable food waste amounted to 80+/-6kg per household per year, and avoidable
      food waste was 103+/-9kg per household per year. Food waste mass was influenced
      significantly by the number of occupants per household (household size) and the
      housing type. The results also indicated that avoidable food waste occurred in
      97% of the households, suggesting that most Danish households could avoid or at
      least reduce how much they generate. Moreover, avoidable and unavoidable food
      waste was more likely to be found in houses containing more than one person than
      in households with only one occupant. 

PMID- 27026494
TI  - Occurrence and treatment efficiency of pharmaceuticals in landfill leachates.
AB  - Landfill leachates might contain pharmaceuticals due to the expired or unwanted
      drugs were disposed of at landfills. These pharmaceuticals might pose a threat to
      soil and groundwater. Therefore, this study investigated the distributions of
      pharmaceutical residues and toxicities among four typical municipal landfill
      leachates. Twenty six pharmaceuticals were investigated in this study and fifteen
      of them were found in all samples from four leachates. In addition, ampicillin
      and methylenedioxymethamphetamine (MDMA) were detected in urban landfills (A1 and
      A2) but were not in rural and suburb landfills (B and C). On the other hand, some
      compounds were much more abundant in suburb/rural landfill leachates than those
      in urban landfills including diclofenac, gemfibrozil and amphetamine. Landfill
      leachate treatment plants could not remove most of the pharmaceuticals
      effectively. Landfill leachates without proper treatments would have significant
      adverse health impacts on human and aquatic life. 

PMID- 27026493
TI  - Risk of food losses and potential of food recovery for social purposes.
AB  - All entities of the food supply chain should be responsible for counteracting
      food waste, therefore a need arises for joint initiatives in this area. To reduce
      food waste, businesses should be supported with a number of procedures for the
      efficient use of food for social purposes that shall be consistent with the law
      in force. Although they can bring about some losses, the following factors
      neither pose a threat to human health nor affect the donation of food for social
      purposes: wrong labelling of packages, food product wrong weight, close-to-end
      expiration date as well as mechanical damage to bulk packages. The purpose of
      this study is to identify such points at each of the four stages of the food
      supply chain (primary production, processing, distribution, sale) where food
      losses can be prevented by donating food to those who need it. A total of 15
      Recovery Points were identified at the above mentioned four stages of the food
      supply chain. Food recovered there is safe to human health, so it can be donated
      for social purposes. 

PMID- 27026495
TI  - An environmentally friendly technology of disassembling electronic components
      from waste printed circuit boards.
AB  - Electronic components (ECs) disassembling from waste printed circuit boards
      (WPCBs) is the first and essential step in WPCBs recycling chain. Over the past
      decades, primitive methods like simply heating WPCBs on a coal-heated plate to
      melt solders are dominated in practice, causing serious environmental pollution
      and also putting a real threat to the human health. In order to solve this
      problem, in this article, an automatic system in pilot-scale for ECs
      disassembling from WPCBs is designed, manufactured, and investigated. This system
      contains two parts: ECs automatic disassembly and off-gas purification.
      Meanwhile, WPCBs from television (i.e., TV-WPCBs) and personal computer (i.e., PC
      WPCBs) are used for disassembling tests, respectively. When the disassembling
      temperature, rotating speed, and incubation time are 265+/-5 degrees C, 10rpm,
      and 8min, respectively, the solder can be completely removed from both TV-WPCBs
      and PC-WPCBs. No pollutant is discharged from this system. Finally, the
      disassembling procedures for ECs from both TV-WPCBs and PC-WPCBs are suggested to
      promote WPCBs disassembling in an environment-friendly way, without threaten the
      environment and human health. 

PMID- 27026496
TI  - Treatment of mechanically sorted organic waste by bioreactor landfill:
      Experimental results and preliminary comparative impact assessment with
      biostabilization and conventional landfill.
AB  - Treatment and disposal of the mechanically sorted organic fraction (MSOF) of
      municipal solid waste using a full-scale hybrid bioreactor landfill was
      experimentally analyzed. A preliminary life cycle assessment was used to compare
      the hybrid bioreactor landfill with the conventional scheme based on aerobic
      biostabilization plus landfill. The main findings showed that hybrid bioreactor
      landfill was able to achieve a dynamic respiration index (DRI)<1000 mgO2/(kgVSh)
      in 20weeks, on average. Landfill gas (LFG) generation with CH4 concentration >55%
      v/v started within 140days from MSOF disposal, allowing prompt energy recovery
      and higher collection efficiency. With the exception of fresh water
      eutrophication with the bioreactor scenario there was a reduction of the impact
      categories by about 30% compared to the conventional scheme. Such environmental
      improvement was mainly a consequence of the reduction of direct and indirect
      emissions from conventional aerobic biostabilization and of the lower amount of
      gaseous loses from the bioreactor landfill. 

PMID- 27026497
TI  - A system dynamics model to evaluate effects of source separation of municipal
      solid waste management: A case of Bangkok, Thailand.
AB  - Municipal solid waste has been considered as one of the most immediate and
      serious problems confronting urban government in most developing and transitional
      economies. Providing solid waste performance highly depends on the effectiveness
      of waste collection and transportation process. Generally, this process involves
      a large amount of expenditures and has very complex and dynamic operational
      problems. Source separation has a major impact on effectiveness of waste
      management system as it causes significant changes in quantity and quality of
      waste reaching final disposal. To evaluate the impact of effective source
      separation on waste collection and transportation, this study adopts a decision
      support tool to comprehend cause-and-effect interactions of different variables
      in waste management system. A system dynamics model that envisages the
      relationships of source separation and effectiveness of waste management in
      Bangkok, Thailand is presented. Influential factors that affect waste separation
      attitudes are addressed; and the result of change in perception on waste
      separation is explained. The impacts of different separation rates on
      effectiveness of provided collection service are compared in six scenarios.
      'Scenario 5' gives the most promising opportunities as 40% of residents are
      willing to conduct organic and recyclable waste separation. The results show that
      better service of waste collection and transportation, less monthly expense,
      extended landfill life, and satisfactory efficiency of the provided service at
      60.48% will be achieved at the end of the simulation period. Implications of how
      to get public involved and conducted source separation are proposed. 

PMID- 27026498
TI  - Role of G protein signaling in the formation of the fibrin(ogen)-integrin
      alphaIIbbeta3-actin cytoskeleton complex in platelets.
AB  - Effective platelet function requires formation of a physical link between
      fibrin(ogen), integrin alphaIIbbeta3, and cytoplasmic actin filaments. We
      investigated the role of the Galphaq, Galphai, and Galpha12/13 families of
      heterotrimeric GTP-binding proteins (G proteins) in the assembly of a ligand
      alphaIIbbeta3-actin cytoskeleton complex. Selective and combined activation of
      the G proteins was achieved by using combinations of various platelet agonists
      and inhibitors. Formation and stability of fibrinogen-alphaIIbbeta3 interaction
      were evaluated by the extent of platelet aggregation and the rate of eptifibatide
      induced platelet disaggregation; association of alphaIIbbeta3 with the
      cytoskeleton was analyzed by western blot. Formation of the fibrin-alphaIIbbeta3
      actin cytoskeleton complex was evaluated by rotational thromboelastometry assay
      in which clot formation was induced by the mixture of reptilase and factor XIIIa.
      We demonstrated that involvement of heterotrimeric G proteins in the formation of
      the ligand-alphaIIbbeta3-cytoskeleton complex depends on whether fibrinogen or
      fibrin serves as the integrin ligand. Formation of the fibrinogen-alphaIIbbeta3
      cytoskeleton complex requires combined activation of at least two G protein
      pathways while the maximal alphaIIbbeta3-cytoskeleton association and the
      strongest alphaIIbbeta3-fibrinogen binding supporting irreversible platelet
      aggregation require combined activation of all three-Galphaq, Galphai, and
      Galpha12/13-G protein families. In contrast, formation of the fibrin
      alphaIIbbeta3-cytoskeleton complex mediating clot retraction is critically
      dependent on the activation of the Galphai family, especially on the activation
      of Galphaz. 

PMID- 27026499
TI  - A systematic review of preoperative determinants of patient-reported pain and
      physical function up to 2 years following primary unilateral total hip
      arthroplasty.
AB  - Although generally considered successful, total hip arthroplasty (THA) can yield
      suboptimal results in terms of pain and function in up to one forth of patients
      suffering from hip osteoarthritis (OA). A thorough understanding of the
      determinants of patient-reported pain and function following THA can help plan
      interventions directed at improving surgical results. Previously published
      systematic reviews do not permit to confidently identify the determinants of THA
      outcomes because of unsatisfactory methodological designs. Therefore, we aimed to
      answer: (1) which preoperative factors are most consistently associated with
      postoperative patient-reported pain and function up to 2 years following primary
      unilateral THA for hip OA. Medline, Pubmed, Embase and CINAHL were screened from
      their respective inception dates until April 2015 using a combination of keywords
      and MESH terms. Criteria for inclusion were: (1) participants with primary
      unilateral THA for hip OA followed for at least 3 months with a maximal follow-up
      of 2 years; (2) validated disease-specific patient-reported outcome measures
      assessing pain and/or disability; (3) identification of determinants obtained via
      multivariate analyses. Methodological quality was assessed using a modified
      version of the methodology checklist for prognostic studies. Twenty-two
      manuscripts were included. Mean score of the methodological quality was 81.0+/
      10.3% (66.7% to 100%). Among socioeconomic determinants, a lower educational
      level was significantly related to worse pain and function (3 out of 3 studies
      evaluating the relationship). Clinical determinants of poor outcomes included
      preoperative levels of pain and physical function (9 out of 12 studies), higher
      body mass index (6 out of 10 studies), presence/greater level of comorbidities (7
      out of 8), worse general health (4 out of 4 studies) and lower radiographic OA
      severity (3 out of 4 studies). Study heterogeneity limited the pooled assessment
      of the strength of associations between the preoperative variables and THA
      outcomes. Studies with moderate-to-high methodological quality allowed to
      identify 6 preoperative variables consistently associated with medium term pain
      and function following THA. This knowledge may assist the management of patients
      at risk of poor results. Further research is required to clarify the force of
      associations between determinants and THA outcomes. LEVEL OF EVIDENCE: Level II.
      Systematic review of cohort studies.

PMID- 27026500
TI  - Conversion of external fixation to open reduction and internal fixation for
      complex distal radius fractures.
AB  - INTRODUCTION: Distal radius fractures are common injuries treated in a multitude
      of ways. One treatment paradigm not extensively studied is initial treatment by
      external fixation (EF) followed by conversion to open reduction internal fixation
      (ORIF). Such a paradigm may be beneficial in damage control situations, when
      there is extensive soft tissue injury, or when appropriate personnel/hospital
      resources are not available for immediate internal fixation. HYPOTHESIS: There is
      no increased risk of infection when converting EF to ORIF in the treatment of
      complex distal radius fractures when conversion occurs early or if EF pin sites
      are overlapped by the definitive fixation. MATERIALS AND METHODS: Using an IRB
      approved protocol, medical records over nine years were queried to identify
      patients with distal radius fractures that had undergone initial EF and were
      later converted to ORIF. Charts were reviewed for demographic data, injury
      characteristics, operative details, time to conversion from EF to ORIF,
      assessment of whether the EF pin sites overlapped the definitive fixation,
      presence of infection after ORIF, complications, and occupational therapy
      measurements of range of motion and strength. RESULTS: In total, 16 patients were
      identified, only one of which developed an infection following conversion to
      ORIF. Fisher's exact testing showed that infection did not depend on open
      fracture, time to conversion of one week or less, presence of EF pin sites
      overlapping definitive fixation, fracture classification, high energy mechanism
      of injury, or concomitant injury to the DRUJ. DISCUSSION: Planned staged
      conversion from EF to ORIF for complex distal radius fractures does not appear to
      result in an increased rate of infection if conversion occurs early or if the EF
      pin sites are overlapped by definitive fixation. This treatment paradigm may be
      reasonable for treating complex distal radius fractures in damage control
      situations, when there is extensive soft tissue injury, or when appropriate
      personnel/hospital resources are not available for immediate internal fixation.
      LEVEL OF EVIDENCE: IV, retrospective case series.

PMID- 27026501
TI  - Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest.
AB  - Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor
      against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin
      that forms lytic pores in host membranes and mediates pneumococcal disease
      pathogenesis by modulating inflammatory responses. Here, we show that
      pneumolysin, which is released during bacterial lysis, induces DNA double strand
      breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX
      phosphorylation (gammaH2AX). Pneumolysin-induced gammaH2AX foci recruit mediator
      of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of
      DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle
      arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated
      non-homologous end joining is inhibited. Further, we observe that cells that were
      undergoing DNA replication harbored DSBs in greater frequency during pneumolysin
      treatment. This observation raises the possibility that DSBs might be arising as
      a result of replication fork breakdown. Additionally, neutralizing the
      oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA
      damage and also cell cycle arrest, indicating that pneumolysin oligomerization is
      important for causing DNA damage. Taken together, this study reveals a previously
      unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with
      implications in the pathophysiology of S. pneumoniae infection. 

PMID- 27026502
TI  - New host records of monacanthid fish for three Kudoa spp. (K. septempunctata, K.
      thyrsites, and K. shiomitsui) prevalent in the olive flounder (Paralichthys
      olivaceus), with the description of K. parathyrsites n. sp. from a black scraper
      (Thamnaconus modestus).
AB  - Kudoa septempunctata (Myxosporean: Multivalvulida) is known as a cause of
      foodborne disease associated with consumption of raw flesh of the olive flounder
      (Paralichthys olivaceus). Knowledge of its life cycle, particularly alternate
      annelid hosts and reservoirs or susceptible fish hosts in natural waters, may
      facilitate disease control in aquaculture farms. Our recent survey of myxosporean
      infection in monacanthid fish in natural waters around Japan revealed infection
      with three kudoid species prevalent in the olive flounder, i.e., K.
      septempunctata, Kudoa thyrsites, and Kudoa shiomitsui. Of the 51 black scrapers
      (Thamnaconus modestus) examined, five fish were infected: two fish with K.
      septempunctata and three with K. thyrsites. One of the fish infected with K.
      septempunctata was also infected with a K. thyrsites-like species. One of the 17
      threadsail filefish (Stephanolepis cirrhifer) and two of four unicorn
      leatherjackets (Aluterus monoceros) were parasitized with K. shiomitsui. Three
      modest filefish (Thamnaconus modestoides) had no kudoid infection. K.
      septempunctata from a black scraper fished in the Inland Sea of Japan off
      Yamaguchi had 6-8 (predominantly 7) shell valves/polar capsules, whereas K.
      septempunctata found in another black scraper from the Sea of Japan off Tottori
      had 5 or 6 (predominantly 6). However, the two isolates displayed identical 18S
      and 28S ribosomal RNA gene (rDNA) nucleotide sequences, which were also identical
      to the isolates from the olive flounder. K. thyrsites from the Inland Sea of
      Japan off Yamaguchi and Sea of Japan off Tottori and K. shiomitsui from the Sea
      of Japan off Shimane and western Pacific Ocean off Kochi were also
      morphologically and genetically characterized. They were found to be coincident
      with the previous reports from olive flounders. Furthermore, the K. thyrsites
      like species found in a black scraper from the Inland Sea of Japan off Yamaguchi
      was morphologically and genetically characterized; a new species, Kudoa
      parathyrsites n. sp., is erected for this species. The relationships of the new
      species with K. thyrsites and related species as well as those of K. shiomitsui
      with Kudoa pericardialis and related species parasitizing the pericardium are
      briefly discussed. 

PMID- 27026503
TI  - alpha-Humulene and beta-elemene from Syzygium zeylanicum (Myrtaceae) essential
      oil: highly effective and eco-friendly larvicides against Anopheles subpictus,
      Aedes albopictus, and Culex tritaeniorhynchus (Diptera: Culicidae).
AB  - Mosquitoes transmit serious pathogens and parasites to humans and animals,
      including malaria, dengue, Japanese encephalitis and filariasis. The extensive
      use of chemical pesticides leads to the development of resistance in mosquito
      vector populations and serious non-target effects on human health and the
      environment. Myrtaceae plants can be a useful reservoir of natural products
      effective against Culicidae young instars. In this research, we evaluated the
      mosquitocidal potential of the essential oil (EO) from Syzygium zeylanicum leaves
      against larvae of three mosquitoes of medical and veterinary importance, the
      malaria vector Anopheles subpictus, the dengue vector Aedes albopictus, and the
      Japanese encephalitis vector Culex tritaeniorhynchus. The chemical composition of
      the EO was analyzed by gas chromatography-mass spectroscopy. GC-MS revealed that
      the S. zeylanicum EO contained at least 18 compounds. The major chemical
      components were alpha-humulene (37.8.5 %) and beta-elemene (10.7 %). The EO had a
      significant toxic effect against early third-stage larvae of An. subpictus, Ae.
      albopictus, and Cx. tritaeniorhynchus, with LC50 values of 83.11, 90.45, and
      97.96 MUg/ml, respectively. The two major constituents extracted from the S.
      zeylanicum EO were tested individually for acute toxicity against larvae of the
      three mosquito vectors. alpha-Humulene and beta-elemene appeared highly effective
      against An. subpictus (LC50 = 6.19 and 10.26 MUg/ml, respectively), followed by
      Ae. albopictus (LC50 = 6.86 and 11.15 MUg/ml) and Cx. tritaeniorhynchus (LC50 =
      7.39 and 12.05 MUg/ml). Furthermore, the EO and its major components was safe
      towards the non-target fish Gambusia affinis; LC50 values were 20374.26, 1024.95,
      and 2073.18 MUg/ml, respectively for EO, alpha-humulene and beta-elemene.
      Overall, this study highlighted that the acute toxicity of S. zeylanicum EO
      towards mosquito larvae was mainly due to the presence of alpha-humulene and beta
      elemene. Furthermore, we pointed out the concrete possibility to exploit these
      two compounds from S. zeylanicum EO as highly effective larvicides against young
      instars of An. subpictus, Ae. albopictus, and Cx. tritaeniorhynchus, with little
      effect on non-target organisms. 

PMID- 27026504
TI  - Efficacy of a topical combination of fipronil, (S)-methoprene, eprinomectin and
      praziquantel (Broadline((r))) against naturally acquired infections with cestodes
      of the genus Joyeuxiella in cats.
AB  - Cats are host to dipylidiid cestodes of the genera Diplopylidium, Dipylidium and
      Joyeuxiella. Broadline((r)), a topical broad-spectrum combination parasiticide
      containing fipronil (8.3 % w/v), (S)-methoprene (10 % w/v), eprinomectin (0.4 %
      w/v) and the cestocide praziquantel (8.3 % w/v), has previously been shown to be
      efficacious against Dipylidium caninum and Diplopylidium spp. in cats. To
      evaluate its efficacy against Joyeuxiella species, a blinded clinical efficacy
      study was conducted according to GCP. All cats had evidence for naturally
      acquired dipylidiid cestode infection as confirmed by pre-treatment examination.
      Cats were allocated randomly to two groups of 13 cats each based on bodyweight:
      Control (untreated) and Broadline((r)) at 0.12 mL/kg bodyweight administered once
      topically. Based on the comparison of helminth counts in the treated and
      untreated cats seven days post treatment, Broadline((r)) demonstrated >99 %
      efficacy (p < 0.01) against mature J. fuhrmanni and J. pasqualei, with 11 and 13
      of the untreated cats harbouring 1 to 102 or 2 to 95 cestodes, respectively. In
      addition, parasite counts indicated 95.9 % efficacy (p = 0.006) against the
      rictularoid nematode Pterygodermatites cahirensis. 

PMID- 27026506
TI  - Photo-activation of Single Molecule Magnet Behavior in a Manganese-based Complex.
AB  - A major roadblock to fully realizing molecular electronic devices is the ability
      to control the properties of each molecule in the device. Herein we report the
      control of the magnetic properties of single-molecule magnets (SMMs), which can
      be used in memory devices, by using a photo-isomerizable diarthylenthene ligand.
      Photo-isomerization of the diarylethene ligand bridging two manganese salen
      complexes with visible light caused a significant change in the SMM behavior due
      to opening of the six-membered ring of diarylethene ligand, accompanied by
      reorganization of the entire molecule. The ring-opening activated the frequency
      dependent magnetization of the complex. Our results are a major step towards the
      realization of molecular memory devices composed of SMMs because the SMM
      behaviour can be turned on and off simply by irradiating the molecule. 

PMID- 27026505
TI  - A method to identify protein antigens of Dermanyssus gallinae for the protection
      of birds from poultry mites.
AB  - The poultry red mite (PRM) Dermanyssus gallinae causes high economic losses and
      is among the most important parasites in poultry farming worldwide. Different
      chemical, physical, and biological strategies try to control the expansion of
      PRM. However, effective solutions to this problem still have to be found. Here,
      we present a method for the development of an immunological control strategy,
      based on the identification of mite protein antigens which elicit antibodies with
      anti-mite activity in the immunized chicken. Hens were immunized with different
      PRM protein extracts formulated with two different adjuvants, and IgY-antibodies
      were isolated from the eggs. A PRM in vitro feeding assay which used chicken
      blood spiked with these IgY-preparations was used to detect antibodies which
      caused PRM mortality. In vitro feeding of mites with IgY isolated from hens
      immunized with PRM extract formulated with one of the adjuvants showed a
      statistically significant increase in the mortality as compared to control mites.
      After the separation of total PRM extracts in two-dimensional gels, several
      protein spots were recognized by such IgY preparations. Ten protein spots were
      subjected to mass spectrometry (MS/MS) for the identification of the
      corresponding proteins. Complete protein sequences were deduced from genomic and
      transcriptomic assemblies derived from high throughput sequencing of total PRM
      DNA and RNA. The results may contribute to the development of an immunological
      control strategy of D. gallinae. 

PMID- 27026507
TI  - Serum n-3 polyunsaturated fatty acids are inversely associated with longitudinal
      changes in depressive symptoms during pregnancy.
AB  - BACKGROUNDS: N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be
      protective for depression during pregnancy. However, there are few data and no
      consensus regarding this association. In this line, we aim to evaluate if the
      concentration of n-3 and n-6 PUFAs, and their ratio, are associated with
      depressive symptoms throughout pregnancy. METHOD: A prospective cohort of 172
      Brazilian women was followed at 5-13th, 20-26th and 30-36th weeks of gestation.
      The presence of depressive symptoms was evaluated using the Edinburgh Postnatal
      Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an
      EPDS score >=11. The concentrations of n-3 [alpha-linolenic acid;
      eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid
      (DHA)] and n-6 PUFAs [linoleic acid; gamma linolenic acid; eicosadienoic acid;
      eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic
      acid] were expressed as absolute (MUg/ml) values. The total n-6/n-3 ratio was
      calculated. Statistical analyses were performed using univariate and adjusted
      random intercept logistic model for each fatty acid (FA) considering the
      longitudinal nature of data. Covariates were selected as potential confounders
      based on their biological plausibility of having an association with the
      concentration of FA and depressive symptoms during pregnancy. RESULTS: The
      prevalence of depressive symptoms was high in all pregnancy trimesters (1st =
      33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA
      concentrations by depressive symptom classification, for each follow-up visit.
      The women presented a 5% decrease in the odds of having depressive symptoms for
      each one-week increase in the gestational age. As individual women progressed
      through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI:
      0.86-0.99), DHA (OR = 0.96; 95% CI: 0.93-0.99), DPA (OR = 0.87; 95% CI: 0.77
      0.99) and total n-3 (OR = 0.98; 95% CI: 0.96-0.99) were associated with a lower
      odds of depressive symptoms, while higher total n-6/n-3 ratio were associated
      with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09-1.79). We
      detected a decrease in the probability of depressive symptoms as concentrations
      of total n-3 FA, alpha-linolenic acid, DPA, and DHA increased. We also observed a
      sharper decline for women with initial greater chance of depressive symptoms
      compared with those with lower chance of having these symptoms. CONCLUSIONS: We
      found a high prevalence of depressive symptoms in low-income Brazilian pregnant
      women and no significant associations between n-6 FA and depressive symptoms.
      Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each
      pregnancy trimester were associated with higher odds of depressive symptoms
      throughout pregnancy.

PMID- 27026508
TI  - Differential expression of skin mucus C-type lectin in two freshwater eel
      species, Anguilla marmorata and Anguilla japonica.
AB  - Two types of lactose-specific lectins, galectin (AJL-1) and C-type lectin (AJL
      2), were previously identified in the mucus of adult Anguilla japonica. Here, we
      compared the expression profiles of these two homologous lectins at the adult and
      juvenile stages between the tropical eel Anguilla marmorata and the temperate eel
      A. japonica. Only one lectin, predicted to be an orthologue of AJL-1 by LC-MS/MS,
      was detected in the mucus of adult A. marmorata. We also found that an
      orthologous gene to AJL-2 was expressed at very low levels, or not at all, in the
      skin of adult A. marmorata. However, we detected the gene expression of an AJL-2
      orthologue in the skin of juvenile A. marmorata, and a specific antibody also
      detected the lectin in the juvenile fish epidermis. These findings suggest that
      expression profiles of mucosal lectins vary during development as well as between
      species in the Anguilla genus.

PMID- 27026509
TI  - Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3beta
      pathway in Subarachnoid Hemorrhage rats.
AB  - Previous studies have shown neuroprotective effects of hypothermia. However, its
      effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain
      unclear. In this study, a SAH rat model was employed to study the effects and
      mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response
      experiments were performed to select the appropriate pramipexole concentration
      and frequency of administration for induction of mild hypothermia (33-36  degrees
      C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB)
      staining were used to detect the effects of pramipexole-induced hypothermia on
      SAH-induced EBI, as well as to study whether controlled rewarming could attenuate
      these effects. Inhibitors targeting the PI3K/AKT/GSK3beta pathway were
      administered to determine whether the neuroprotective effect of pramipexole
      induced hypothermia was mediated by PI3K/AKT/GSK3beta signaling pathway. The
      results showed that intraperitoneal injection of pramipexole at 0.25 body weight
      once per 8 hours was found to successfully and safely maintain rats at mild
      hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell
      death, blood-brain barrier damage and neurobehavioral deficits in a
      PI3K/AKT/GSK3beta signaling-dependent manner. Therefore, we may conclude that
      pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats
      via PI3K/AKT/GSK3beta signaling pathway.

PMID- 27026511
TI  - Reply, Letter to the Editor - The impact of sarcopenia and myosteatosis on
      outcomes of unresectable pancreatic cancer or distal cholangiocarcinoma.

PMID- 27026510
TI  - Effect of restrictive versus liberal transfusion strategies on outcomes in
      patients with cardiovascular disease in a non-cardiac surgery setting: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To compare patient outcomes of restrictive versus liberal blood
      transfusion strategies in patients with cardiovascular disease not undergoing
      cardiac surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES:
      Randomised controlled trials involving a threshold for red blood cell transfusion
      in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL,
      PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO
      International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical
      Trials Register. Authors were contacted for data whenever possible. TRIAL
      SELECTION: Published and unpublished randomised controlled trials comparing a
      restrictive with liberal transfusion threshold and that included patients with
      cardiovascular disease. DATA EXTRACTION AND SYNTHESIS: Data extraction was
      completed in duplicate. Risk of bias was assessed using Cochrane methods.
      Relative risk ratios with 95% confidence intervals were presented in all meta
      analyses. Mantel-Haenszel random effects models were used to pool risk ratios.
      MAIN OUTCOME MEASURES: 30 day mortality, and cardiovascular events. RESULTS: 41
      trials were identified; of these, seven included data on patients with
      cardiovascular disease. Data from a further four trials enrolling patients with
      cardiovascular disease were obtained from the authors. In total, 11 trials
      enrolling patients with cardiovascular disease (n=3033) were included for meta
      analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519).
      The pooled risk ratio for the association between transfusion thresholds and 30
      day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with
      little heterogeneity (I(2)=14%). The risk of acute coronary syndrome in patients
      managed with restrictive compared with liberal transfusion was increased (nine
      trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I(2)=0%).
      CONCLUSIONS: The results show that it may not be safe to use a restrictive
      transfusion threshold of less than 80 g/L in patients with ongoing acute coronary
      syndrome or chronic cardiovascular disease. Effects on mortality and other
      outcomes are uncertain. These data support the use of a more liberal transfusion
      threshold (>80 g/L) for patients with both acute and chronic cardiovascular
      disease until adequately powered high quality randomised trials have been
      undertaken in patients with cardiovascular disease. REGISTRATION: PROSPERO
      CRD42014014251.

PMID- 27026512
TI  - Efficacy of neoadjuvant hypofractionated radiotherapy in patients with locally
      advanced myxoid liposarcoma.
AB  - BACKGROUND: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive
      compared with other soft tissue sarcomas (STS). The use of preoperative
      hypofractionated radiotherapy 5 * 5 Gy for five consecutive days, and then
      immediate surgery in patients with locally advanced STS showed a good local
      control rate. The main objective of our work was to assess the efficacy of
      hypofractionated radiotherapy in preoperative setting in patients with locally
      advanced primary MLPS. METHODS: From February 1999 to March 2014, 32 patients
      with primary MLPS were treated with preoperative hypofractionated radiotherapy
      for 5 consecutive days followed by immediate surgery (median dose 5 * 5 Gy).
      Median size of the tumor 10.5 cm. In one patient the tumor was located on the
      upper extremity, the other (31 patients) had their tumors located on the lower
      extremity. RESULTS: In 90% patients histologically negative surgical margins (R0)
      were obtained. 34% patients had distant recurrence of the disease, local
      recurrence was found in 9.3% of the patients. 5-year local relapse-free survival
      rate was 90% and overall survival was 68%. In all analyzed surgical specimens the
      radiotherapy response features (hyalinization, fibrosis, paucicelularity,
      hemorrhages, dilatation of vessels) were detected. We have not found
      statistically significant differences in terms of OS and LRFS for RCC component,
      tumor grade, BCL2, TP53, postsurgery necrosis and tumor size. In postradiotherapy
      specimens significantly higher positivity of TP53 expression was detected as
      compared to primary biopsies. CONCLUSION: Combined therapy with hypofractionated
      radiotherapy followed by immediate surgery seems to be effective therapy in MLPS
      demonstrating good local control and pathological response to therapy.

PMID- 27026513
TI  - A case of acquired angioedema possibly associated with adenocarcinoma of the
      colon.

PMID- 27026514
TI  - Association of T-regulatory cells and CD23/CD21 expression with vitamin D in
      children with asthma.
AB  - BACKGROUND: Children with asthma have low vitamin D levels; however, we do not
      know whether low vitamin D is associated with impaired T-regulatory (Treg) cell
      population or high IgE receptors (CD23 and CD21) on B cells. OBJECTIVE: To
      examine Treg cell function, CD23 and CD21 receptors, vitamin D, and vitamin D
      regulating enzymes in children with asthma. METHODS: Sixty children (2-6 years
      old) with asthma and 60 age-matched healthy children were selected as study
      participants. After collecting demographic and clinical data, blood samples were
      collected. Treg cells and CD23/CD21 expressions were evaluated by flow cytometry,
      25-hydroxyvitamin D3 (25[OH]D3) was quantified by high-performance liquid
      chromatography, and cytokines and total IgE were estimated by enzyme-linked
      immunosorbent assay. Messenger RNA (mRNA) expressions of FOXP3, CD23, CD21,
      vitamin D receptors, and vitamin D-regulating enzymes were assessed by reverse
      transcription-polymerase chain reaction. RESULTS: The 25(OH)D3 concentrations and
      proportion of Treg cells were lower (P < .05) among children with asthma. In
      contrast, the proportions of B cells with CD23 and CD21 expression were higher (P
      < .05) in patients with asthma compared with controls. Interleukin 10 and
      transforming growth factor beta were also altered in asthma. The mRNA expression
      of CD23, CD21, and vitamin D receptors was up-regulated, whereas mRNA expression
      of vitamin D-regulating enzymes, CYP2R1, CYP27B1, and vitamin D binding protein
      (except CYP24A1) were up-regulated among children with asthma. CONCLUSION: The
      current study found impaired Treg cell population and high numbers of B cells
      with IgE receptors (CD23 and CD21) and altered regulatory cytokines in children
      with asthma, suggesting impaired immune regulation.

PMID- 27026515
TI  - Clinical application of navigator-gated three-dimensional balanced turbo-field
      echo magnetic resonance cholangiopancreatography at 3 T: prospective
      intraindividual comparison with 1.5 T.
AB  - OBJECTIVE: To evaluate and compare the clinical utility of balanced turbo-field
      echo (BTFE) magnetic resonance cholangiopancreatography (MRCP) sequences obtained
      at 3 and 1.5 T. METHODS: We acquired three-dimensional (3D) BTFE MRCP scans with
      a navigator-gated technique at 3 T on a different day after 1.5 T in 39
      consecutive patients. Two radiologists independently rated the image quality and
      visibility of anatomical structures (right and left hepatic duct, cystic duct,
      gallbladder, common bile duct, and main pancreatic duct) using a four-point
      scale. For quantitative analysis, the signal-to-noise ratio (SNR), contrast-to
      noise ratio (CNR), and acquisition time were evaluated. RESULTS: All visual
      scores tended to be higher for 1.5 T than 3 T images. There was a significant
      difference in the image quality and the depiction of the main pancreatic duct (p
      < 0.01). The image acquisition time was significantly shorter for 3 T than 1.5 T
      (199.3 +/- 40.1 vs. 264.0 +/- 86.5 s, p < 0.01). There was no significant
      difference in SNR and CNR. CONCLUSIONS: 3D-BTFE MRCP scans acquired at 3 T were
      of sufficient image quality with respect to the biliary tree. SNR and CNR were
      comparable on 3 and 1.5 T scans, although the acquisition time was significantly
      shorter with the 3 T scanner.

PMID- 27026516
TI  - A primer on the use of dual-energy CT in the evaluation of commonly encountered
      neoplasms.
AB  - Technical improvements in the acquisition and display of dual-energy computed
      tomography (DECT) have made this technique increasingly applicable to clinical
      practice, particularly in the setting of oncologic imaging. DECT allows for
      qualitative and quantitative analysis of tissue composition beyond the standard
      anatomical evaluation possible with single-energy computed tomography. For
      example, DECT can be used to interrogate iodine and calcium concentrations and to
      increase iodine signal, which makes many pathologic processes more conspicuous
      and provides improved understanding of internal structure within mass lesions. A
      working understanding of common postprocessing DECT displays will allow
      radiologists to maximize the additional diagnostic information available in DECT
      examinations. In this article, we describe common strategies for DECT
      interrogation by organ system, which may improve the conspicuity and
      understanding of suspected malignancies.

PMID- 27026517
TI  - Practices of pharmaceutical waste generation and discarding in households across
      Portugal.
AB  - This work is the first nationwide study in Portugal on pharmaceutical waste
      generated at households, exploring people's attitudes and risk perception. The
      waste audit was carried out from September to November 2014, targeting
      pharmaceutical products kept by a sample of families (n = 244). This campaign was
      an assignment of VALORMED, the non-profit association that manages waste and
      packaging from expired and unused pharmaceutical products collected by the
      pharmacies. On average, each household kept at home 1097 g of pharmaceutical
      products, of which 20% were in use, 72% were not in use, and 8% were mostly
      expired products ready to discard. Face-to-face interviews with householders
      showed that 69% of the respondents claimed returning pharmaceutical waste to the
      local pharmacy. However, this figure is overrated, probably owing to a possible
      'good answer' effect. The barriers identified to proper disposal were mainly
      established routines and lack of close disposal points. This study also provides
      an insight into the Portuguese awareness and daily practices concerning
      pharmaceutical waste, which is the cornerstone of any future strategy to reduce
      the release of active pharmaceutical ingredients into ecosystems.

PMID- 27026518
TI  - Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA
      Nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Proteinuria is an independent predictor for IgA
      nephropathy (IgAN) progression. Urine albumin-to-creatinine ratio (ACR), protein
      to-creatinine ratio, and 24-hour urine protein excretion (UPE) are widely used
      for proteinuria evaluation in clinical practice. Here, we evaluated the
      association of these measurements with clinical and histologic findings of IgAN
      and explored which was the best predictor of IgAN prognosis. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Patients with IgAN were followed up for >=12
      months, were diagnosed between 2003 and 2012, and had urine samples available
      (438 patients). Spot urine ACR, protein-to-creatinine ratio, and 24-hour UPE at
      the time of renal biopsy were measured on a Hitachi Automatic Biochemical
      Analyzer 7180 (Hitachi, Yokohama, Japan). RESULTS: In our patients, ACR, protein
      to-creatinine ratio, and 24-hour UPE were highly correlated (correlation
      coefficients: 0.71-0.87). They showed good relationships with acknowledged
      markers reflecting IgAN severity, including eGFR, hypertension, and the biopsy
      parameter (Oxford severity of tubular atrophy/interstitial fibrosis parameter).
      However, only ACR presented with positive association with the Oxford segmental
      glomerulosclerosis/adhesion parameter and extracapillary proliferation lesions.
      The follow-up time was 37.0 (22.0-58.0) months, with the last follow-up on April
      18, 2014. In total, 124 patients reached the composite end point (30% eGFR
      decline, ESRD, or death). In univariate survival analysis, ACR consistently had
      better performance than protein-to-creatinine ratio and 24-hour UPE as
      represented by higher area under the curve using time-dependent survival
      analysis. When adjusted for well known risk factors for IgAN progression, ACR was
      most significantly associated with the composite end point (hazard ratio, 1.56
      per 1-SD change of standard normalized square root-transformed ACR; 95%
      confidence interval, 1.29 to 1.89; P<0.001). Compared with protein-to-creatinine
      ratio and 24-hour UPE, addition of ACR to traditional risk factors resulted in
      more improvement in the predictive ability of IgAN progression (c statistic:
      ACR=0.70; protein-to-creatinine ratio =0.68; 24-hour UPE =0.69; Akaike
      information criterion: ACR=1217.85; protein-to-creatinine ratio =1229.28; 24-hour
      UPE =1234.96; P<0.001). CONCLUSIONS: In IgAN, ACR, protein-to-creatinine ratio,
      and 24-hour UPE had comparable association with severe clinical and histologic
      findings. Compared with protein-to-creatinine ratio and 24-hour UPE, ACR showed
      slightly better performance in predicting IgAN progression.

PMID- 27026519
TI  - Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI
      during Hospitalization among Patients Presenting to the Emergency Department.
AB  - BACKGROUND AND OBJECTIVES: Emergency departments (EDs) have a growing role in
      hospital admissions, but few studies address AKI biomarkers in the ED. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Patients admitted to the internal medicine
      service were enrolled during initial workup in the ED at Robert-Bosch-Hospital,
      Stuttgart, Germany. Daily serum creatinine (sCr) and urine output (UO) were
      recorded for AKI classification by Kidney Disease Improving Global Outcomes
      (KDIGO) criteria. Cystatin C, kidney injury molecule-1, liver-type fatty acid
      binding protein, and neutrophil gelatinase-associated lipocalin were measured in
      blood and urine, and IL-18, insulin-like growth factor-binding protein 7
      (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and [TIMP-2]?[IGFBP7]
      were measured in urine collected at enrollment, after 6 hours, and the following
      morning. Association between these biomarkers and the end point of moderate
      severe AKI (KDIGO stage 2-3) occurring within 12 hours of each sample collection
      was examined using generalized estimating equation logistic regression.
      Performance for prediction of the AKI end point using two previously validated
      [TIMP-2]-[IGFBP7] cutoffs was also tested. RESULTS: Of 400 enrolled patients, 298
      had sufficient sCr and UO data for classification by KDIGO AKI criteria: AKI
      stage 2 developed in 37 patients and AKI stage 3 in nine patients. All urinary
      biomarkers, sCr, and plasma cystatin C had statistically significant (P<0.05)
      odds ratios (ORs) for the AKI end point. In a multivariable model of the urine
      biomarkers and sCr, only [TIMP-2]?[IGFBP7] and sCr had statistically significant
      ORs. Compared with [TIMP-2]?[IGFBP7]<0.3 (ng/ml)(2)/1000, values between 0.3 and
      2.0 (ng/ml)(2)/1000 indicated 2.5 (95% confidence interval [95% CI], 1.1 to 5.2)
      times the odds for the AKI end point and values >2.0 (ng/ml)(2)/1000 indicated
      11.0 (95% CI, 4.4 to 26.9) times the odds. Addition of [TIMP-2]?[IGFBP7] to a
      clinical model significantly improved area under the receiver-operating
      characteristic curve from 0.67 (95% CI, 0.61 to 0.78) to 0.77 (95% CI, 0.72 to
      0.86) (P<0.001); however, including both markers in the model was not
      significantly different from including either marker alone. CONCLUSIONS: Urinary
      [TIMP-2]?[IGFBP7] with pre-established cutoffs provides valuable information
      about risk for imminent AKI in the ED that is complementary to sCr and clinical
      risk factors.

PMID- 27026520
TI  - Longitudinal Study of Serum Uric Acid, Nutritional Status, and Mortality in
      Maintenance Hemodialysis Patients.
AB  - BACKGROUND AND OBJECTIVES: We hypothesized that longitudinal changes in uric acid
      (UA) may have independent associations with changes in nutritional parameters
      over time and consequently, long-term survival of patients on maintenance
      hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a
      retrospective, longitudinal cohort study of a clinical database containing the
      medical records of patients on maintenance hemodialysis receiving dialysis
      between June of 1999 and December of 2012 in a single center; 200 patients (130
      men and 70 women) with a median age of 69.0 (interquartile range, 59.3-77.0)
      years old were included in the study. Dietary intake, biochemical markers of
      nutrition, anthropometric measurements, and UA levels were recorded at 0, 6, 12,
      18, 24, 30, and 36 months followed by 15 additional months of clinical
      observations. The patients were followed until January 31, 2015 (median follow-up
      was 38.0 [interquartile range, 30.0-46.8] months). RESULTS: In a linear mixed
      effects model adjusted for baseline demographics and clinical parameters, each
      1.0-mg/dl longitudinal increase in UA was associated with a 13.4% slower rate of
      decline in geriatric nutritional risk index (GNRI) levels over 3 years of
      observation (95% confidence interval [95% CI], 0.11 to 0.39; P<0.001 for UA *
      time interaction). UA remained associated with the rate of change in GNRI, even
      after controlling for C-reactive protein. During the follow-up, 87 (43.5%) all
      cause and 38 (19.0%) cardiovascular deaths were reported. For each 1.0-mg/dl
      increase in serum UA over time, the multivariate adjusted all-cause mortality
      hazard ratio using Cox models with the effect of time-varying risk was 0.83 (95%
      CI, 0.74 to 0.95; P<0.01), which continued to be significant, even after
      including the baseline GNRI levels in this model: 0.89 (95% CI, 0.79 to 0.98;
      P=0.02). CONCLUSIONS: Longitudinal changes in serum UA seem to track with changes
      in nutritional status over time, and these changes are associated with survival
      of patients on maintenance hemodialysis. An increase in serum UA levels over time
      is accompanied by improvement of nutritional status and lower mortality rate.

PMID- 27026521
TI  - Bone Parameters and Risk of Hip and Femur Fractures in Patients on Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Patients on hemodialysis have a high rate of hip
      fractures. In this study, we performed a contemporary analysis of mineral and
      bone parameters and their relationship to hip and femur fracture risk. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis treated between
      2000 and 2013 in Fresenius Medical Care North America facilities were included.
      Predictors were on the basis of data as of December 31 of each baseline year and
      time-averaged values of selected laboratory parameters and medication doses
      throughout the year. Four period cohorts were constructed from baseline years:
      2000, 2003, 2006, and 2009. Follow-up for each cohort was <=3 years. RESULTS: The
      incidence of hip and femur fractures remained generally unchanged (P=0.40),
      except among patients who were white and >65 years of age, in whom the rate
      decreased significantly over the 14-year period (P<0.01). Results from combined
      multivariable models indicated that the lowest quartiles of time-averaged intact
      parathyroid hormone were independently associated with higher hip fracture risk
      (intact parathyroid hormone =181-272 pg/ml: hazard ratio, 1.20; 95% confidence
      interval [95% CI], 1.03 to 1.41 and intact parathyroid hormone <181 pg/ml: hazard
      ratio, 1.20; 95% CI, 1.01 to 1.44; referent third quartile, 273 to <433 pg/ml).
      The lowest quartile of time-averaged serum calcium was also associated with
      higher risk (calcium <8.7 mg/dl; hazard ratio, 1.17; 95% CI, 1.00 to 1.37)
      compared with the referent third quartile of 9.1 to <9.5 mg/dl. CONCLUSIONS: We
      found an association between lower levels of intact parathyroid hormone and serum
      calcium and greater risk for hip and femur fractures among patients on
      hemodialysis. These findings support additional research toward elucidating long
      term safety of treatment approaches for hyperparathyroidism in patients with
      ESRD.

PMID- 27026522
TI  - A Qualitative Study to Explore Patient and Staff Perceptions of Intradialytic
      Exercise.
AB  - BACKGROUND AND OBJECTIVES: Randomized, controlled trials show that regular
      exercise is beneficial for patients on hemodialysis. Intradialytic exercise may
      have additional benefits, such as amelioration of treatment-related symptoms.
      However, the factors that influence the implementation of intradialytic exercise
      are largely unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Individual
      semistructured interviews were conducted with a purposive sample of patients on
      hemodialysis who had participated in a pilot randomized, controlled trial on
      intradialytic exercise and dialysis staff that worked in the unit during the
      trial. The trial took place from July to December of 2014 and enrolled 31
      patients. Interviews were conducted from April to December of 2014. Interview
      coding followed an inductive and broad-based approach. Thematic analysis was used
      to group codes into common themes, first individually and then, across staff and
      patient interviews. RESULTS: Twenty-five patients and 11 staff were interviewed.
      Three themes common to both groups emerged: support, norms (expected practices)
      within the dialysis unit, and the role of the dialysis nurse. The support of the
      kinesiologist enhanced patients' confidence and sense of capability and was a key
      component of implementation. However, the practice of initiating exercise at the
      start of the shift was a barrier to staff participation. Staff focused on the
      technical aspects of their role in intradialytic exercise, whereas patients
      viewed encouragement and assistance with intradialytic exercise as the staff's
      role. An additional theme of no time (for staff to participate in intradialytic
      exercise) was influenced by its low priority in their workflow and the demands of
      the unit. The staff's emphasis on patients setting up their own equipment and
      enhanced social interaction among participants were additional themes that
      conveyed the unintended consequences of the intervention. CONCLUSIONS: The
      kinesiologist-patient interactions and staff readiness for intradialytic exercise
      were important factors in the implementation of intradialytic exercise.
      Understanding how unit workflow and the personal values of staff can influence
      implementation may improve the design of intradialytic exercise interventions.

PMID- 27026525
TI  - Three-dimensional imaging of the intracellular assembly of a functional viral RNA
      replicase complex.
AB  - Positive-strand RNA viruses, which can be devastating pathogens in humans,
      animals and plants, replicate their genomes on intracellular membranes. Here, we
      describe the three-dimensional ultrastructural organization of a tombusvirus
      replicase in yeast, a valuable model for exploring virus-host interactions. We
      visualized the intracellular distribution of a viral replicase protein using
      metal-tagging transmission electron microscopy, a highly sensitive nanotechnology
      whose full potential remains to be developed. These three-dimensional images show
      how viral replicase molecules are organized when they are incorporated into the
      active domains of the intracellular replication compartment. Our approach
      provides a means to study protein activation mechanisms in cells and to identify
      targets for new antiviral compounds.

PMID- 27026523
TI  - mTORC1 is necessary but mTORC2 and GSK3beta are inhibitory for AKT3-induced axon
      regeneration in the central nervous system.
AB  - Injured mature CNS axons do not regenerate in mammals. Deletion of PTEN, the
      negative regulator of PI3K, induces CNS axon regeneration through the activation
      of PI3K-mTOR signaling. We have conducted an extensive molecular dissection of
      the cross-regulating mechanisms in axon regeneration that involve the downstream
      effectors of PI3K, AKT and the two mTOR complexes (mTORC1 and mTORC2). We found
      that the predominant AKT isoform in CNS, AKT3, induces much more robust axon
      regeneration than AKT1 and that activation of mTORC1 and inhibition of GSK3beta
      are two critical parallel pathways for AKT-induced axon regeneration.
      Surprisingly, phosphorylation of T308 and S473 of AKT play opposite roles in
      GSK3beta phosphorylation and inhibition, by which mTORC2 and pAKT-S473 negatively
      regulate axon regeneration. Thus, our study revealed a complex neuron-intrinsic
      balancing mechanism involving AKT as the nodal point of PI3K, mTORC1/2 and
      GSK3beta that coordinates both positive and negative cues to regulate adult CNS
      axon regeneration. 

PMID- 27026526
TI  - Vulnerability of newly synthesized proteins to proteostasis stress.
AB  - The capacity of the cell to produce, fold and degrade proteins relies on
      components of the proteostasis network. Multiple types of insults can impose a
      burden on this network, causing protein misfolding. Using thermal stress, a
      classic example of acute proteostatic stress, we demonstrate that ~5-10% of the
      soluble cytosolic and nuclear proteome in human HEK293 cells is vulnerable to
      misfolding when proteostatic function is overwhelmed. Inhibiting new protein
      synthesis for 30 min prior to heat-shock dramatically reduced the amount of heat
      stress induced polyubiquitylation, and reduced the misfolding of proteins
      identified as vulnerable to thermal stress. Following prior studies in C. elegans
      in which mutant huntingtin (Q103) expression was shown to cause the secondary
      misfolding of cytosolic proteins, we also demonstrate that mutant huntingtin
      causes similar 'secondary' misfolding in human cells. Similar to thermal stress,
      inhibiting new protein synthesis reduced the impact of mutant huntingtin on
      proteostatic function. These findings suggest that newly made proteins are
      vulnerable to misfolding when proteostasis is disrupted by insults such as
      thermal stress and mutant protein aggregation.

PMID- 27026528
TI  - Interleukin-29: Just an extra string in the bow of Th17 cells or a target for
      therapeutic exploitation?

PMID- 27026529
TI  - Fluorescein-labeled Bacitracin and Daptomycin Conjugates: Synthesis, Fluorescence
      Imaging and Evaluation.
AB  - BACKGROUND: Previously, glycopeptides antibiotics such as vancomycin, ramoplanin
      and an antifungal antibiotic nystatin have been studied for their diagnostic and
      therapeutic potential. OBJECTIVE: To further explore the diagnostic and
      chemotherapeutic potential of other antibiotics we have now employed daptomycin,
      a lipopetide antibiotic and bacitracin, a polypeptide antibiotic in uptake and
      vitality tests on human cell lines. METHOD: Fluorescent conjugates of bacitracin
      and daptomycin were synthesized using fluorescein isothiocynate (FITC) for
      confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting
      (FACS). The cellular uptake of the synthesized daptomycin and bacitracin
      conjugates was studied on seven human cell lines, two healthy and five malignant
      using CLSM and FACS. To examine the cell membrane damage caused by the conjugates
      FACS experiments were carried out using propidium iodide. RESULTS: The uptake
      pattern was different for both antibiotics for all the cell lines. The
      cytoplasmic uptake of daptomycin conjugate was lower than the bacitracin
      conjugate, resulting in decreased cell membrane damage. CONCLUSION: No
      preferential uptake into malignant or healthy cells was found for the two
      different antibiotic conjugates and the uptake patterns were also different
      between the two antibiotics. However, the lower cytotoxicity and different uptake
      mechanism makes daptomycin conjugate a prospective candidate for further study as
      a diagnostic agent for various intracellular infections.

PMID- 27026530
TI  - Amyloid light-chain amyloidosis presenting as abdominal bloating: a case report.
AB  - BACKGROUND: We present a case of amyloid light-chain amyloidosis with occult
      plasma cell dyscrasia, with the rare initial presentation of gastroparesis. While
      amyloidosis is known to affect the gastrointestinal system, rarely do patients
      present with gastrointestinal symptoms as their first symptom. To the best of our
      knowledge, this is the first such case reported with a definitive diagnosis made
      on gastroscopy. CASE PRESENTATION: A 52-year-old Malay man with abdominal
      bloating, early satiety, and weight loss was found to have significant
      gastroparesis. He had a past medical history of stable non-ischemic
      cardiomyopathy. Results from initial screening were negative for common causes of
      gastroparesis, such as diabetes or offending medications. Gastroscopy did not
      show any mechanical gastric outlet obstruction. Our patient subsequently
      developed symptoms of postural giddiness, which then prompted further
      investigations for possible autonomic dysfunction. These finally revealed
      evidence of systemic involvement, including postural hypotension, speckled
      myocardium with infiltrative cardiomyopathy on a transthoracic echocardiogram,
      and multifocal motor neuropathy on nerve conduction studies, from which he had
      been relatively asymptomatic. These findings were collectively suggestive of
      infiltrative disease. Retrospective Congo red staining of a gastric biopsy
      specimen confirmed the diagnosis of gastric amyloidosis. The final diagnosis was
      amyloid light-chain amyloidosis secondary to plasma cell dyscrasia, which was
      confirmed by bone marrow examination. Our patients was started on chemotherapy
      and prokinetic agents, with some improvement in gastrointestinal symptoms on
      follow-up. CONCLUSION: We present this case to highlight that, although rare,
      gastroparesis can be the initial sole presentation of amyloidosis. It is
      important for the internist, gastroenterologist, and hematologist to consider
      amyloidosis as a differential diagnosis in the investigation of gastroparesis and
      to be vigilant in monitoring for other systemic involvement.

PMID- 27026527
TI  - Epidermal growth factor suppresses intestinal epithelial cell shedding through a
      MAPK-dependent pathway.
AB  - Cell shedding from the intestinal villus is a key element of tissue turnover that
      is essential to maintain health and homeostasis. However, the signals regulating
      this process are not well understood. We asked whether shedding is controlled by
      epidermal growth factor receptor (EGFR), an important driver of intestinal growth
      and differentiation. In 3D ileal enteroid culture and cell culture models (MDCK,
      IEC-6 and IPEC-J2 cells), extrusion events were suppressed by EGF, as determined
      by direct counting of released cells or rhodamine-phalloidin labeling of
      condensed actin rings. Blockade of the MEK-ERK pathway, but not other downstream
      pathways such as phosphoinositide 3-kinase (PI3K) or protein kinase C (PKC),
      reversed EGF inhibition of shedding. These effects were not due to a change in
      cell viability. Furthermore, EGF-driven MAPK signaling inhibited both caspase
      independent and -dependent shedding pathways. Similar results were found in vivo,
      in a novel zebrafish model for intestinal epithelial shedding. Taken together,
      the data show that EGF suppresses cell shedding in the intestinal epithelium
      through a selective MAPK-dependent pathway affecting multiple extrusion
      mechanisms. EGFR signaling might be a therapeutic target for disorders featuring
      excessive cell turnover, such as inflammatory bowel diseases.

PMID- 27026532
TI  - Does acute tobacco smoking prevent cue-induced craving?
AB  - BACKGROUND: Smoking cessation aids appear to be limited in their ability to
      prevent craving triggered by exposure to smoking-associated stimuli; however, the
      extent to which cue-induced cravings persist following denicotinized or nicotine
      containing tobacco smoking is not known. METHODS: Thirty (17 male) ?12-hour
      abstinent dependent smokers completed two sessions during which they smoked a
      nicotine-containing or denicotinized cigarette. Instructions regarding the
      nicotine content of the cigarette varied across sessions, and all participants
      were exposed to a neutral cue followed by a smoking cue after cigarette
      consumption. Craving was assessed before and after cigarette consumption and cue
      exposure. RESULTS: Reduced intentions to smoke were associated with both nicotine
      expectancy (p<0.05) and nicotine administration (p<0.01), while reduced
      withdrawal-related craving was uniquely associated with nicotine administration
      (p<0.05). Smoking-associated stimuli increased craving regardless of nicotine
      expectancy or administration (p-values<0.001). CONCLUSIONS: While both nicotine
      pharmacology and expectancy appear to contribute to craving reduction associated
      with acute tobacco smoking, neither smoking-related nicotine administration nor
      expectation prevents increases in craving following exposure to smoking
      associated stimuli. These findings suggest that cue-induced craving may be
      resistant to various pharmacological and psychological interventions.

PMID- 27026533
TI  - Hypertensive retinopathy in a transgenic angiotensin-based model.
AB  - Severe hypertension destroys eyesight. The RAS (renin-angiotensin system) may
      contribute to this. This study relied on an established angiotensin, AngII
      (angiotensin II)-elevated dTGR (double-transgenic rat) model and same-background
      SD (Sprague-Dawley) rat controls. In dTGRs, plasma levels of AngII were
      increased. We determined the general retinal phenotype and observed degeneration
      of ganglion cells that we defined as vascular degeneration. We also inspected
      relevant gene expression and lastly observed alterations in the outer blood
      retinal barrier. We found that both scotopic a-wave and b-wave as well as
      oscillatory potential amplitude were significantly decreased in dTGRs, compared
      with SD rat controls. However, the b/a-wave ratio remained unchanged.
      Fluorescence angiography of the peripheral retina indicated that exudates, or
      fluorescein leakage, from peripheral vessels were increased in dTGRs compared
      with controls. Immunohistological analysis of blood vessels in retina whole-mount
      preparations showed structural alterations in the retina of dTGRs. We then
      determined the general retinal phenotype. We observed the degeneration of
      ganglion cells, defined vascular degenerations and finally found differential
      expression of RAS-related genes and angiogenic genes. We found the expression of
      both human angiotensinogen and human renin in the hypertensive retina. Although
      the renin gene expression was not altered, the AngII levels in the retina were
      increased 4-fold in the dTGR retina compared with that in SD rats, a finding with
      mechanistic implications. We suggest that alterations in the outer blood-retinal
      barrier could foster an area of visual-related research based on our findings.
      Finally, we introduce the dTGR model of retinal disease.

PMID- 27026534
TI  - Erratum to: Reassessing the risk of natalizumab-associated PML.

PMID- 27026535
TI  - A Mixed-Methods Approach to the Development, Refinement, and Pilot Testing of
      Social Networks for Improving Healthy Behaviors.
AB  - BACKGROUND: Mobile health (mHealth) has shown promise as a way to deliver weight
      loss interventions, including connecting users for social support. OBJECTIVE: To
      develop, refine, and pilot test the Social Pounds Off Digitally (POD) Android app
      for personalized health monitoring and interaction. METHODS: Adults who were
      overweight and obese with Android smartphones (BMI 25-49.9 kg/m(2); N=9) were
      recruited for a 2-month weight loss pilot intervention and iterative usability
      testing of the Social POD app. The app prompted participants via notification to
      track daily weight, diet, and physical activity behaviors. Participants received
      the content of the behavioral weight loss intervention via podcast. In order to
      re-engage infrequent users (did not use the app within the previous 48 hours),
      the app prompted frequent users to select 1 of 3 messages to send to infrequent
      users targeting the behavioral theory constructs social support, self-efficacy,
      or negative outcome expectations. Body weight, dietary intake (2 24-hr recalls),
      and reported calories expended during physical activity were assessed at baseline
      and 2 months. All participants attended 1 of 2 focus groups to provide feedback
      on use of the app. RESULTS: Participants lost a mean of 0.94 kg (SD 2.22, P=.24)
      and consumed significantly fewer kcals postintervention (1570 kcal/day, SD 508)
      as compared to baseline (2384 kcal/day, SD 993, P=.01). Participants reported
      expending a mean of 171 kcal/day (SD 153) during intentional physical activity
      following the intervention as compared to 138 kcal/day (SD 139) at baseline, yet
      this was not a statistically significant difference (P=.57). There was not a
      statistically significant correlation found between total app entries and percent
      weight loss over the course of the intervention (r=.49, P=.19). Mean number of
      app entries was 77.2 (SD 73.8) per person with a range of 0 to 219. Messages
      targeting social support were selected most often (32/68, 47%), followed by self
      efficacy (28/68, 41%), and negative outcome expectations (8/68, 12%). Themes from
      the focus groups included functionality issues, revisions to the messaging
      system, and the addition of a point system with rewards for achieving goals.
      CONCLUSIONS: The Social POD app provides an innovative way to re-engage
      infrequent users by encouraging frequent users to provide social support.
      Although more time is needed for development, this mHealth intervention can be
      disseminated broadly for many years and to many individuals without the need for
      additional intensive in-person hours.

PMID- 27026536
TI  - 6-week radiographs unsuitable for diagnosis of suspected scaphoid fractures.
AB  - INTRODUCTION: Six week follow-up radiographs are a common reference standard for
      the diagnosis of suspected scaphoid fractures. The main purpose of this study was
      to evaluate the interobserver reliability and diagnostic performance
      characteristics of 6-weeks radiographs for the detection of scaphoid fractures.
      In addition, two online techniques for evaluating radiographs were compared.
      MATERIALS AND METHODS: A total of 81 orthopedic surgeons affiliated with the
      Science of Variation Group assessed initial and 6-week scaphoid-specific
      radiographs of a consecutive series of 34 patients with suspected scaphoid
      fractures. They were randomized in two groups for evaluation, one used a standard
      website showing JPEG files and one a more sophisticated image viewer (DICOM). The
      goal was to identify the presence or absence of a (consolidated) scaphoid
      fracture. Interobserver reliability was calculated using the multirater kappa
      measure. Diagnostic performance characteristics were calculated according to
      standard formulas with CT and MRI upon presentation in the emergency department
      as reference standards. RESULTS: The interobserver agreement of 6-week
      radiographs for the diagnosis of scaphoid fractures was slight for both JPEG and
      DICOM (k = 0.15 and k = 0.14, respectively). The sensitivity (range 42-79 %) and
      negative predictive value (range 79-94 %) were significantly higher using a DICOM
      viewer compared to JPEG images. There were no differences in specificity (range
      53-59 %), accuracy (range 53-58 %), and positive predictive value (range 14-26 %)
      between the groups. CONCLUSIONS: Due to low agreement between observers for the
      recognition of scaphoid fractures and poor diagnostic performance, 6-week
      radiographs are not adequate for evaluating suspected scaphoid fractures. The
      online evaluation of radiographs using a DICOM viewer seem to improve diagnostic
      performance characteristics compared to static JPEG images and future reliability
      and diagnostic studies should account for variation due to the method of
      delivering medical images. LEVEL OF EVIDENCE: Diagnostic level II.

PMID- 27026537
TI  - Transposed-Letter Priming Across Inflectional Morpheme Boundaries.
AB  - This study reports findings from two experiments testing whether a transposed
      letter (TL) priming effect can be obtained when the transposition occurs across
      morphological boundaries. Previous studies have primarily tested derivationally
      complex words or compound words, but have not examined a more rule-based and
      productive morphological structure, i.e., inflectionally complex words, using
      masked priming. Experiment 1 tested TL priming with nonword primes and inflected
      targets (FOCUSING). Nonword primes were formed by transposing letters either
      within the root morpheme (fcousing) or across two morphemes (focuisng).
      Experiment 2 used the same nonword primes, but had the root words as targets
      (FOCUS). Both experiments showed similar TL priming effects for within-morpheme
      and across-boundary positions, indicating that morphological decomposition takes
      place only after letter positions in a word have been assigned. This finding
      provides additional evidence to previous research testing derived and compound
      words showing TL priming regardless of the position of transposition.

PMID- 27026538
TI  - The impact of autophagy on cell death modalities in CRL-5876 lung adenocarcinoma
      cells after their exposure to gamma-rays and/or erlotinib.
AB  - In most patients with lung cancer radiation treatment is used either as single
      agent or in combination with radiosensitizing drugs. However, the mechanisms
      underlying combined therapy and its impact on different modes of cell death have
      not yet been fully elucidated. We aimed to examine effects of single and combined
      treatments with gamma-rays and erlotinib on radioresistant CRL-5876 human lung
      adenocarcinoma cells with particular emphasis on cell death. CRL-5876 cells were
      treated with gamma-rays and/or erlotinib and changes in cell cycle, DNA repair
      dynamics, ultrastructure, nuclear morphology and protein expression were
      monitored at different time points. To reveal the relationship between types of
      cell death that arise after these treatments, autophagy was blocked with
      chloroquine. We found that higher dose of gamma-rays causes G2/M arrest while
      adding of erlotinib to this treatment decreases the number of cells in S phase.
      Impact of erlotinib on kinetics of disappearance of irradiation-induced DNA
      double strand breaks is reflected in the increase of residual gamma-H2AX foci
      after 24 h. gamma-rays provoke cytoprotective autophagy which precedes
      development of senescence. Erlotinib predominantly induces apoptosis and enlarges
      the number of apoptotic cells in the irradiated CRL-5876 cells. Chloroquine
      improved cytotoxicity induced by radiation and erlotinib, increased apoptosis and
      decreased senescence in the CRL-5876 cells. The results obtained on CRL-5876
      cells indicate significant radiosensitizing effect of erlotinib and suggest that
      chloroquine in the combination with the above treatments may have an additional
      antitumor effect in lung adenocarcinoma.

PMID- 27026539
TI  - Traffic-related heavy metals uptake by wild plants grow along two main highways
      in Hunan Province, China: effects of soil factors, accumulation ability, and
      biological indication potential.
AB  - This study was performed to investigate pollution of traffic-related heavy metals
      (HMs-Zn, Pb, Cu, Cr, and Cd) in roadside soils and their uptake by wild plants
      growing along highways in Hunan Province, China. For this, we analyzed the
      concentration and chemical fractionation of HMs in soils and plants. Soil samples
      were collected with different depths in the profile and different distances from
      highway edge. And leaves and barks of six high-frequency plants were collected.
      Results of the modified European Community Bureau of Reference (BCR) showed that
      the mobile fraction of these HMs was in the order of Cd > Pb > Zn > Cu > Cr. A
      high percentage of the mobile fraction indicates Cd, Pb, and Zn were labile and
      available for uptake by wild plants. The total concentration and values of risk
      assessment code (RAC) showed that Cd was the main risk factor, which were in the
      range high to very high risk. The accumulation ability of HMs in plants was
      evaluated by the biological accumulation factor (BAF) and the metal accumulation
      index (MAI), and the results showed that all those plant species have good phyto
      extraction ability, while accumulation capacity for most HMs plants tissues was
      bark > leaf. The highest MAI value (5.99) in Cinnamomum camphora (L) Presl
      indicates the potential for bio-monitoring and a good choice for planting along
      highways where there is contamination with HMs. 

PMID- 27026540
TI  - Efficient biodegradation of phenanthrene by a novel strain Massilia sp. WF1
      isolated from a PAH-contaminated soil.
AB  - A novel phenanthrene (PHE)-degrading strain Massilia sp. WF1, isolated from PAH
      contaminated soil, was capable of degrading PHE by using it as the sole carbon
      source and energy in a range of pH (5.0-8.0), temperatures (20-35  degrees C),
      and PHE concentrations (25-400 mg L(-1)). Massilia sp. WF1 exhibited highly
      effective PHE-degrading ability that completely degraded 100 mg L(-1) of PHE over
      2 days at optimal conditions (pH 6.0, 28  degrees C). The kinetics of PHE
      biodegradation by Massilia sp. WF1 was well represented by the Gompertz model.
      Results indicated that PHE biodegradation was inhibited by the supplied lactic
      acid but was promoted by the supplied carbon sources of glucose, citric acid, and
      succinic acid. Salicylic acid (SALA) and phthalic acid (PHTA) were not utilized
      by Massilia sp. WF1 and had no obvious effect on PHE biodegradation. Only two
      metabolites, 1-hydroxy-2-naphthoic acid (1H2N) and PHTA, were identified in PHE
      biodegradation process. Quantitatively, nearly 27.7 % of PHE was converted to
      1H2N and 30.3 % of 1H2N was further metabolized to PHTA. However, the PHTA
      pathway was broken and the SALA pathway was ruled out in PHE biodegradation
      process by Massilia sp. WF1. 

PMID- 27026541
TI  - Characteristics, sources, and health risk of polycyclic aromatic hydrocarbons in
      urban surface dust: a case study of the city of Xi'an in Northwest China.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants.
      Urban surface dust is an important carrier of PAHs. To investigate the
      characteristics, sources, and health risk of PAHs in urban surface dust, this
      study collected urban surface dust samples from Xi'an, the largest city in
      Northwest China and one of the cities with severe smog occurrences in China. The
      total concentration of 16 US EPA priority PAHs (?16PAHs) ranged from 5.0 to 48
      mg/kg, with an average of 14 mg/kg. The seven carcinogenic PAHs accounted for 21
      to 65 % of the ?16PAHs. Higher levels of PAHs were found in its industrial,
      traffic, and mixed commercial and traffic districts. The PAHs were dominated by
      four-ring PAHs, and the predominant components were Fla, Phe, Chy, and Pyr.
      Multivariate statistical analyses showed that the PAHs originated mainly from the
      combustion of fossil fuel as well as coal and wood, and petroleum emission. The
      toxic equivalency quantities (TEQs) of urban surface dustborne PAHs ranged from
      0.25 to 8.3 mg/kg, with a mean of 1.8 mg/kg. The 95 % upper confidence limit of
      incremental lifetime cancer risk (ILCR) due to human exposure to urban surface
      dustborne PAHs was 8.2 * 10(-5) for children and 7.3 * 10(-5) for adults. 

PMID- 27026542
TI  - The influence of environmental parameters in the biocolonization of the Mithraeum
      in the roman masonry of casa di Diana (Ostia Antica, Italy).
AB  - The microclimatic parameters (Ta, RH, E, and CO2) reflect the indoor quality of
      the environment. Their relationship, connected with the design of the building,
      can facilitate the growth of photo/heterotrophic organisms and therefore
      facilitate the increase of the relative CO2 production. Taking this into account,
      the impact of biological proliferation in a historical building is discussed for
      the Mithraeum of "Casa di Diana" in the archaeological site of Ostia Antica,
      which is subjected to guided tours. In this work, for the first time, we propose
      a study on biological monitoring to evaluate the contribution of bioactivity to
      air quality, with the objective to increase the comfort of visitors and to open
      the site for more than one day per week, suggesting possible tools providing a
      good compromise between building conservation and human comfort. In the sense, it
      has been possible to distinguish the contribution of the plants from the one
      deriving from humans: high values of carbon dioxide have been recorded during the
      night and its scarce removal during the day (air flow). The window present is not
      sufficient to eliminate the CO2, involving concentrations of CO2 relatively high
      in comparison to the proposed limits and guidelines defined by law. The obtained
      results strongly encouraged the elimination of flora in order to increase the
      comfort of visitors and to open the house for more than one day per week.
      Although, this process involves an important economic effort, the present study
      allows making an objective decision which has an important value in a cultural
      heritage management. Graphical Abstract CO2 contribute by bioactivity as damage
      to human health. 

PMID- 27026543
TI  - Is foliar spray of proline sufficient for mitigation of salt stress in Brassica
      juncea cultivars?
AB  - The effects of foliar application of proline (20 mM) on growth, physio
      biochemical, and yield parameters were assessed in two Brassica juncea (L.) Czern
      & Coss cultivars, namely, Varuna and RH-30, at different levels (2.8, 4.2, or 5.6
      dsm(-1)) of NaCl in soil. At 29 days after sowing (DAS), plants were sprayed with
      either 20 mM proline or water in the presence or absence of NaCl stress. The NaCl
      negatively affected parameters related to growth, photosynthesis, and yield in
      both varieties but more in RH-30 than in Varuna. Exogenous application of proline
      counteracted the effects of salt stress in Varuna only, by increasing the
      antioxidative capacity of the plants. Moreover, proline was not effective in
      alleviating the detrimental effects of higher salt concentrations on the studied
      parameters. Proline application to unstressed plants increased growth,
      photosynthesis, and yield parameters in both varieties; however, the effects were
      more prominent in Varuna than in RH-30. 

PMID- 27026544
TI  - Analysis of Zn, Cd, As, Cu, Pb, and Fe in snails as bioindicators and soil
      samples near traffic road by ICP-OES.
AB  - Snails are used as biological indicators of the environment pollution for heavy
      metals. Living snail samples were collected from different sites at the city of
      Irbid-Jordan and classified according to their morphological features including
      Helix pelasga, Eobania vermiculata, Xeropicta derbentina, Oychilus, Xerocrassa
      seetzenii, Xerocrassa simulata, and Pila. Zn, Cd, As, Cu, Pb, and Fe levels were
      measured by inductively coupled plasma-optical emission spectroscopy. Results
      indicated that metal concentrations in all snail shell samples were with an
      average and range for Zn 22.4 (6.5-105.5) MUg g(-1), Cd 7.8 (0.4-48.1) MUg g(-1),
      As 25.9 (0.7-248.5) MUg g(-1), Cu 15.1 (1.6-69.0) MUg g(-1), Pb 0.4 (0.2-1.7) MUg
      g(-1), and Fe 119.6 (14.0-1102.0) MUg g(-1), whereas, in soil samples, the
      average and range for Zn 204.0 (12.0-709.0) MUg g(-1), Cd 5.7 (0.2-39.5) MUg g(
      1), As 3.2 (1.8-5.2) MUg g(-1), Cu 22.1 (2.3-77.4) MUg g(-1), Pb 0.2 (0.1-0.3)
      MUg g(-1), and Fe 242.4 (25.0-680.0) MUg g(-1). 

PMID- 27026545
TI  - Histopathological study of toxic effects of carbaryl on digestive tract of
      Bufotes variabilis (Anura: Bufonidae).
AB  - Due to the negative effects of pesticide usage in environment, i.e., decline in
      amphibian populations, this study was designed to examine histopathologic changes
      following carbaryl exposure for 96 h in the digestive tract of variable toad,
      Bufotes variabilis. After exposure to single doses of carbaryl (low dose 50
      MUg/g, medium dose 100 MUg/g, and high dose: 200 MUg/g), the toads were
      euthanized and dissected and digestive tract samples were quickly removed.
      Histopathology revealed esophageal vacuolization and necrosis in esophageal
      cells. Hemorrhage was also observed in the esophagus. In the stomach, necrosis in
      the glandular epithelium, congested blood vessels, edema among gastric glands,
      dilated tips of the mucosal epithelial layer, gastric glandular atrophy, and
      hemorrhage were found. In the intestine, edema within villi, hemorrhage,
      inflammation, vacuolization, and necrosis in epithelial cells of villi were
      detected. This study clearly showed that carbaryl caused adverse effects on the
      digestive tract of B. variabilis in all dose groups. 

PMID- 27026546
TI  - Photocatalytic oxidation of selected gas-phase VOCs using UV light, TiO2, and
      TiO2/Pd.
AB  - Heterogeneous photocatalytic oxidation systems using titanium dioxide (TiO2) have
      been extensively studied for the removal of several volatile organic compounds
      (VOCs). The addition of noble metals such as palladium on TiO2 may improve
      photocatalytic activity by increasing charge separation efficiency. In this work,
      palladium was impregnated on TiO2 and the efficiency of the new catalyst was
      tested and compared with that of pure TiO2. Pd was impregnated on TiO2 by the
      reduction method, using NaBH4, and was characterized by XRD, XPS, UV-Vis, and H2
      chemisorption. The photocatalytic tests were performed in an annular coated-wall
      reactor using octane, isooctane, n-hexane, and cyclohexane at inlet
      concentrations varying from 100 to 120 ppmv. Compared with pure TiO2 film, the
      photocatalytic activity of TiO2 impregnated with 1 wt% of palladium was improved.
      All the aforementioned analytical techniques confirmed the presence of Pd
      incorporated into the structure of TiO2, and the conversion rates were studied in
      a broad range of residence times, yielding up to 90 % or higher rates in 40 s of
      residence time, thus underscoring the relevant contribution of the technology.

PMID- 27026547
TI  - Total, chemical, and biological oxygen consumption of the sediments in the Ziya
      River watershed, China.
AB  - Sediment oxygen demand (SOD) is a critical dissolved oxygen (DO) sink in many
      rivers. Understanding the relative contributions of the biological and chemical
      components of SOD would improve our knowledge of the potential environmental harm
      SOD could cause and allow appropriate management systems to be developed. A
      various inhibitors addition technique was conducted to measure the total,
      chemical, and biological SOD of sediment samples from 13 sites in the Ziya River
      watershed, a severely polluted and anoxic river system in the north of China. The
      results showed that the major component of SOD was chemical SOD due to iron
      predominate. The ferrous SOD accounted for 21.6-78.9 % of the total SOD and 33.26
      96.79 % of the chemical SOD. Biological SOD represented 41.13 % of the overall
      SOD averagely. Sulfide SOD accounted for 1.78-45.71 % of the total SOD and it was
      the secondary predominate of the chemical SOD. Manganous SOD accounted for 1.2
      16.6 % of the total SOD and it was insignificant at many sites. Only four kinds
      of benthos were collected in the Ziya River watershed, resulting from the low DO
      concentration in the sediment surface due to SOD. This study would be helpful for
      understanding and preventing the potential sediment oxygen depletion during river
      restoration. 

PMID- 27026548
TI  - Research on dye wastewater decoloration by pulse discharge plasma combined with
      charcoal derived from spent tea leaves.
AB  - Pulsed discharge plasma (PDP) combined with charcoal (PDP-charcoal) was employed
      to treat dye wastewater, with methyl orange (MO) as the model pollutant. The
      charcoal was prepared using spent tea leaves and was characterized by scanning
      electron microscopy, Fourier-transform infrared spectroscopy, and Boehm titration
      to investigate the adsorption and catalytic characteristics before and after
      adsorption and PDP treatment. The prepared charcoal exhibited a high MO
      adsorption capacity, and the adsorption process followed the pseudo-second-order
      kinetic model and the Freundlich model. The MO decoloration efficiency reached
      69.8 % within 7.5 min of treatment in the PDP-charcoal system, whereas values of
      29.2 and 25.9 % were achieved in individual PDP and charcoal systems,
      respectively. The addition of n-butanol and H2PO4 (-) presented inhibitive
      effects on MO decoloration in the PDP system. However, these effects were much
      weaker in the PDP-charcoal system. In addition, the effects of charcoal on O3 and
      H2O2 formation were evaluated, and the results showed that both the O3 and H2O2
      concentrations decreased in the presence of charcoal. The MO decomposition
      intermediates were analyzed using UV-Vis spectrometry and GC-MS. 1,4
      Benzoquinone, 4-nitrophenol, 4-hydroxyaniline, and N,N'-dimethylaniline were
      detected. A possible pathway for MO decomposition in this system was proposed. 

PMID- 27026549
TI  - Chloride ion-driven transformation from Ag3PO4 to AgCl on the hydroxyapatite
      support and its dual antibacterial effect against Escherichia coli under visible
      light irradiation.
AB  - Visible light-driven photocatalytic inactivation of Escherichia coli was
      performed using hydroxyapatite-supported Ag3PO4 nanocomposites (Ag3PO4/HA). The
      antibacterial performance was evaluated by the methods of zone of inhibition
      plates and minimum inhibitory concentration test. X-ray diffraction (XRD) and
      transmission electron microscopy (TEM) were employed to investigate the
      instability and transformation of the nanocomposite by comparing the crystalline,
      phase, and the morphology before and after exposure to Luria-Bertani culture
      medium under visible light irradiation. Ag3PO4 nanoparticles on the support were
      found to be shortly transformed into AgCl due to high chloride concentration of
      Luria-Bertani culture medium. The AgCl/HA nanocomposite showed both excellent
      intrinsic antibacterial performance contributed by the released silver ions and
      visible light-induced photocatalytic disinfection toward E. coli cells. This dual
      antibacterial function mechanism was validated by trapping the hydroxyl free
      radical and detecting the silver ions during the photocatalytic antibacterial
      process. The morphological change of E. coli cells in different reaction
      intervals was obtained by scanning electron microscopy (SEM) to complementally
      verify photocatalytic inactivation of E. coli. This work suggests that an
      essential comparison study is required for the antibacterial materials before and
      after the photocatalytic inactivation of bacterial cells using Ag3PO4
      nanoparticles or Ag3PO4-related nanocomposites in mediums containing high
      concentration chloride ions. 

PMID- 27026550
TI  - Enhancement of sludge anaerobic biodegradability by combined microwave-H2O2
      pretreatment in acidic conditions.
AB  - The aim of this study was to increase the sludge disintegration and reduce the
      cost of microwave (MW) pretreatment. Thermodynamic analysis of MW hydrolysis
      revealed the best fit with a first-order kinetic model at a specific energy of
      18,600 kJ/kg total solids (TS). Combining H2O2 with MW resulted in a significant
      increment in solubilization from 30 to 50 % at 18,600 kJ/kg TS. The pH of H2O2
      assisted MW-pretreated sludge (MW + H2O2) was in the alkaline range (pH 9-10),
      and it made the sludge unfavorable for subsequent anaerobic digestion and
      inhibits methane production. In order to nullify the alkaline effect caused by
      the MW + H2O2 combination, the addition of acid was considered for pH adjustment.
      H2O2-assisted MW-pretreated sludge in acidic conditions (MW + H2O2 + acid) showed
      a maximum methane production of 323 mL/g volatile solids (VS) than others during
      anaerobic biodegradability. A cost analysis of this study reveals that MW + H2O2
      + acid was the most economical method with a net profit of 59.90 ?/t of sludge. 

PMID- 27026551
TI  - [Self-Management in Patients With Chronic Kidney Disease].
AB  - Chronic kidney disease (CKD) patients typically self-manage their disease-care
      program. Self-management requires the investment of considerable time and energy
      in health management and in following the multifaceted CKD treatment regimen.
      CKD, a progressive disease, is classified into five stages that correspond to the
      five stages of decline in kidney function, as measured using the glomerular
      filtration rate (GRF). Each of these stages requires that a patient modify his /
      her lifestyle and shoulder the responsibility for day-to-day health management
      tasks. Key to promoting self-management is the partnership and collaboration
      between healthcare providers and patients. Tasks in this partnership include
      patient assessment and communication, regimen adherence, emotional management,
      negotiation of care plans, and the enhancement of self-efficacy, with the aims of
      creating positive changes in behavior, promoting correct symptoms interpretation
      and reporting, and promoting the appropriate use of resources. Nurses may help
      patients maneuver this initially frightening and sometimes difficult terrain with
      strategies that are tailored to each CKD stage. 

PMID- 27026552
TI  - [Using eHealth in the Continuity Care of Chronic Kidney Disease: Opportunities
      and Considerations].
AB  - Kidney disease is a common complication of chronic diseases among adult and
      elderly populations. As early-stage chronic kidney disease (CKD) is asymptomatic,
      CKD patients are frequently unaware of their condition and fail to implement
      requisite self-care in a timely fashion. Furthermore, the shortage of case
      management manpower and difficulties in follow-up have led to high incidence
      rates for CKD worldwide. Integrative and continuous care is key to preventing
      CKD. How to implement this care effectively is a challenge. However, innovative
      technologies, online information, and cloud technology are increasingly providing
      access to good-quality healthcare beyond the traditional limitations of time and
      location. This environment is not only increasing the participation of patients
      in their care and collaboration among healthcare team members but is also
      improving the continuity, accessibility, and promptness of care service in order
      to promote the effectiveness of disease management. While the primary aim of
      innovative technologies is to make healthcare more cost-effective, it is also
      causing disparities in healthcare. Within the high-tech e-healthcare system, the
      ability of patients to utilize these new services relates directly to their
      health behaviors and quality of care. Thus, emergent e-healthcare system services
      should be made as patient-centered as possible in order to maximize the benefits
      in terms of both cost and patient care. Furthermore, improving the eHealth
      literacy of patients is crucial to promoting innovative technology within
      healthcare services. 

PMID- 27026553
TI  - [Applying the Strategies of Helping Relationship From Significant Others in
      Patients With Chronic Kidney Disease].
AB  - The absence of easily perceived symptoms in the early stages of chronic kidney
      disease (CKD) causes low levels of awareness and treatment of this disease.
      Therefore, adherence to measures that may prevent disease progression, i.e.,
      lifestyle changes, regular clinic visits, and timely medication administration,
      is often low among early-stage CKD patients. However, continuous assistance from
      significant others through trusting, understanding, sharing, and coaching
      assistance may promote a healthy lifestyle and prevent progression of the
      disease. The necessary characteristics of significant others include
      dependability, credibility, and positivity. Significant others may use their
      understanding, caring, faith, and honesty to help patients face CKD and improve
      self-care efficacy. This article discusses the assistance that significant others
      may provide to CKD patients, including warning mechanisms, target setting,
      encouragement, and feedback. By developing the functions of supervision,
      companionship, and support, significant others may help patients live a healthier
      life and improve their medical compliance and thus postpone disease progression. 

PMID- 27026554
TI  - [The Process of Developing Clinical Practice Guidelines: Example of the "2015
      Taiwan Chronic Kidney Disease Clinical Guidelines"].
AB  - Clinical practice guidelines (CPGs), representing the current best-practice
      guidelines and recommendations for care, are supported by systematic review and
      evidence-based research. CPGs provide an effective and efficient approach to
      caring for patients and improving quality of care. Recently, the National Health
      Insurance Administration and National Institutes of Health developed CPGs for
      major diseases in Taiwan. This paper introduces the process that was used to
      develop one of these CPGs, the Taiwan Chronic Kidney Disease Clinical Guidelines,
      which was published in 2015. Further, we introduce the general development of
      published nursing guidelines in Taiwan. These CPGs are expected to initiate
      various renal-care guidelines and to promote the quality of renal care in the
      country. 

PMID- 27026555
TI  - [Promoting Living Kidney Transplantation].
AB  - Kidney transplantation is the best approach for treating patients with end stage
      renal disease, offering patients the best chance of returning to normal health.
      While the techniques used in kidney transplantation surgery are mature and highly
      successful, there is a severe shortage of donor organs. Statistics show a serious
      imbalance between organ donations and patients on the waiting list for organ
      transplantation. Moreover, evidence from empirical studies has shown a better
      transplantation outcome for patients who receive living donor transplantation
      than for those who receive organs from cadavers. Although using relatives as
      donors offers an effective way to reduce the problem of organ shortage, this
      strategy faces many challenges and many other factors affect the promotion of
      living donor transplantation. This article elaborates how cultural and
      psychological factors, kidney transplantation awareness, and ethics and laws
      impact upon living kidney donations and then proposes coping strategies for
      promoting living kidney transplantation. 

PMID- 27026556
TI  - [Effects of Auricular Acupressure on Improving the Sleep Quality of Puerperae].
AB  - BACKGROUND: Puerperae exhibit generally poor sleep quality. Previous studies have
      shown auricular acupressure as effective in improving the sleep problems of
      nurses, college students, and elderly indigenous Taiwanese women. However, no
      study has yet examined the effectiveness of auricular acupressure in improving
      the sleep quality of postpartum women. PURPOSE: To explore the efficacy of
      auricular acupressure (AA) on puerperae who were affected by sleep disturbance.
      METHODS: A prospective quasi-experimental design was used and 60 puerperae with
      insomnia who scored at least 5 on the Chinese of version of the Pittsburgh Sleep
      Quality Index (CPSQI) were recruited at one postpartum centre (a "doing-the
      month" care centre) in northern Taiwan. The experimental group (n=30) received
      pasted auricular magnetic beads and acupressure on the Shenmen, Xin, and Shen
      points. The control group (n=30) received general nursing directions about
      insomnia only. All participants were assessed using the CPSQI prior to the
      intervention and on the 21st post-intervention day. The intervention effects were
      analysed using the Generalized Estimating Equation (GEE). RESULTS: After three
      weeks of the AA intervention, the mean global PSQI score had decreased
      significantly more in the experimental group than in the control group (p<.05).
      Furthermore, experimental-group participants reported better sleep quality
      (p<.05), longer total sleep time (p<.001) and lower sleep disturbance (p<.05)
      than their control-group peers. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The
      present pilot study found complementary AA to be an effective intervention for
      treating puerperae with insomnia. This non-pharmacological and nonintrusive
      intervention for improving sleep disturbance in puerperae promotes the quality of
      sleep.

PMID- 27026557
TI  - [The Continued Breastfeeding Experiences of Women Who Suffer From Breast
      Abscess].
AB  - BACKGROUND: Up to 11% of women with mastitis develop a breast abscess, which
      obviously affects breastfeeding. Therefore, this is a potentially significant
      issue for women's health. Women with breast abscesses suffer from severe pain.
      Pain is the most significant factor causing the termination of breastfeeding. The
      experience of women with breast abscesses who continued to breastfeed may provide
      valuable insights/guidance to women who are currently in the same or similar
      situations. PURPOSE: This study explores the continuous breastfeeding experience
      of women with breast abscesses. METHODS: We collected qualitative data from 10
      qualified female participants using 60-90 minute, in-depth interviews that were
      conducted between April 2012 and June 2012 in a central medical center. All
      interviews were recorded and transcribed verbatim. Content analysis was used to
      analyze and categorize the major themes. RESULTS: Results were generalized into
      the following seven themes: (1) experiencing uncomfortable breast pain; (2)
      feeling helpless to manage the abnormal breast symptoms; (3) relying on the
      concept of motherhood to support continued breastfeeding; (4) feeling shocked
      about the process of diagnosis and treatment; (5) facing the doubts and
      difficulties regarding continuing to breastfeed; (6) experiencing the assistance
      of the support system for breastfeeding; (7) returning to a normal pattern of
      life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings provide nurses with a
      deeper understanding of the biological and psychological behaviors and social
      support system experiences of women with breast abscesses who continue to
      breastfeed. Study results may serve as a reference for nurses in providing mother
      centered breastfeeding care.

PMID- 27026558
TI  - [Comparing the Health Needs of Older Aboriginal and Older Ethnic Chinese
      Individuals in Taiwan].
AB  - BACKGROUND: Providing healthcare to older people is an essential policy in
      Taiwan. Previous studies have assessed the health needs of older people residing
      in urban areas. Evidence related to the differences in healthcare needs between
      older aboriginal and older ethnic Chinese people in Taiwan is insufficient. As
      both groups exhibit mutually distinct physical and socio-cultural attributes,
      understanding their different health needs is necessary to provide tailored and
      effective healthcare. PURPOSE: To investigate the distinct health needs of older
      aboriginal and older ethnic Chinese using a comprehensive health-needs assessment
      tool. METHODS: A cross-sectional study design was used. Older people aged 65 or
      over were proportionally sampled from communities. The Elderly Assessment System
      Care Standard instrument was used to collect data through interviews held in
      participant homes or in community activity centers between October 20th and
      December 20th, 2011. RESULTS: A total of 180 older people were recruited. A
      majority of participants had at least one chronic disease, disability, or
      frailty. Across a range of dimensions and categories of health needs, older
      aboriginal people had statistically significant higher health needs than non
      aboriginal ones. However, older ethnic Chinese participants had higher levels of
      need in the domains of housing/financing and social participation/isolation.
      Regression analysis found that independence, risk of frailty, and risk of falls
      explained the majority of health needs, with R2 values of 64% and 69.6% for older
      aboriginal and older ethnic Chinese participants, respectively. However, the
      respective impact of these three categories on overall health needs varied
      between the two groups. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Based on our
      findings, healthcare providers should focus on improving the self-care
      capabilities of older aboriginal people and on reducing the risk of breakdowns in
      care for older ethnic Chinese people in order to enhance the quality of elderly
      care in Taiwan.

PMID- 27026559
TI  - [Nurses' Innovation Acceptance of Barcode Technology].
AB  - BACKGROUND: Healthcare organizations have increasingly adopted barcode technology
      to improve care quality and work efficiency. Barcode technology is simple to use,
      so it is frequently used in patient identification, medication administration,
      and specimen collection processes. PURPOSE: This study used a technology
      acceptance model and innovation diffusion theory to explore the innovation
      acceptance of barcode technology by nurses. METHODS: The data were collected
      using a structured questionnaire with open-ended questions that was based on the
      technology acceptance model and innovation diffusion theory. The questionnaire
      was distributed to and collected from 200 nurses from March to May 2014. Data on
      laboratory reporting times and specimen rejection rates were collected as well.
      RESULTS: Variables that were found to have a significant relationship (p<.001)
      with innovation acceptance included (in order of importance): perceived
      usefulness (r=.722), perceived ease of use (r=.720), observability (r=.579),
      compatibility (r=.364), and trialability (r=.344). N-level nurses demonstrated
      higher acceptance than their N1 and N2 level peers (F=3.95, p<.05). Further, the
      mean laboratory reporting time decreased 109 minutes (t=10.03, p<.05) and the
      mean specimen rejection rate decreased from 2.18% to 0.28%. CONCLUSIONS /
      IMPLICATIONS FOR PRACTICE: The results revealed that barcode technology has been
      accepted by nurses and that this technology effectively decreases both laboratory
      reporting times and specimen rejection rates. However, network speed and workflow
      should be further improved in order to benefit clinical practice.

PMID- 27026560
TI  - [An Exploration of Working Conditions and Flexible System for Hospital Nurses].
AB  - BACKGROUND: The lack of sufficient numbers of professional nurses in the
      healthcare system in Taiwan is an issue that affects the sustainability of this
      system and that relates closely to working conditions. PURPOSE: The present study
      explores the expectations that nurses hold with regard to working conditions and
      the operation of a flexible system in hospitals. METHODS: A literature review and
      focus-group interviews were used to develop the questionnaire Working Conditions
      and Flexible System. A total of 1,150 copies of this questionnaire were
      distributed to practicing nurses using stratified random sampling, with 1,146
      valid copies returned for a valid recovery rate of 99.65%. RESULTS: The results
      show that the expectations of participants concerning working conditions and a
      flexible system focus on the 6 factors of task, numerical, divisional, temporal,
      wages, and leading flexibility. The total mean was 4.35 (SD=0.42). The means for
      the 6 types of flexibility were all greater than 4.0. Participants deemed
      flexibility to be of high importance. The demographic variables hospital, work
      location, age, education level, work position, work unit, and total work years
      all affected the 6 types of flexibility significantly. CONCLUSIONS: The present
      study supports that the retention of nurses is significantly associated with
      working conditions and the operation of a flexible system. Administrators and
      mangers must create positive working conditions and a flexible system in order to
      enhance the retention and career development of nurses.

PMID- 27026561
TI  - [Perceptions of Nursing Image Held by Third and Fourth-Year Baccalaureate Nursing
      Students and Related Factors].
AB  - BACKGROUND: Prior studies indicate that the perception of nursing image heldx by
      nursing students influences the attitudes of these students toward nursing care
      and their future professional role identity as nurses. However, few studies have
      investigated this issue in Taiwan in recent years. PURPOSE: To examine the
      perceptions of nursing image held by third- and fourth-year baccalaureate nursing
      students and the factors that influence these perceptions. METHODS: The present
      study employed a cross-sectional survey design. Questionnaires were administered
      to a total of 219 nursing students who were currently enrolled at a university in
      southern Taiwan. Descriptive statistics, chi-square test, Pearson product-moment
      correlation, multiple linear regression, and simple logistic regression analysis
      were conducted using SPSS 12.0, Chinese version. RESULTS: The mean age of
      participants was 22.2 years; most were fourth-year students (58.9%) and female
      (85.8%). Regarding the images of nursing, most participants indicated that
      current nursing work possesses characteristics that include: "being a
      profession", "emphasizing care and concern for patients", "requiring
      meticulousness", and "requiring emotional control". In terms of perceptions of
      professional nurses, most participants considered nurses to be: "constantly
      needing to progress and innovate", "capable of caring for and respecting others",
      "independent and self-conscious", and "sufficiently intelligent". The present
      study identified significant differences between third- and fourth-year students
      in only three variables, with a larger percentage of fourth-year students
      perceiving nurses as "dedicated and willing to sacrifice", "handmaidens to
      doctors", and "not bossy and stern" than their third-year peers. In addition, it
      demonstrated significantly positive relationships between the dependent variables
      of traditional/bureaucratic image and advanced professional image and the
      independent variables of willingness to become nursing professionals after
      graduation, satisfaction with the school's clinical courses arrangement, and
      learning-environmental factors. Furthermore, "more job opportunities", as a
      reason for admission to nursing school and learning-environmental factors,
      explained 11.7% of the variance in participant perceptions of
      traditional/bureaucratic image and "encouragement from family and friends", as a
      reason for admission to nursing school and learning-environmental factors,
      explained 18.2% of the variance in participant perceptions of advanced
      professional image. Finally, both "traditional/bureaucratic image" and "advanced
      professional image" were predictors of participant willingness to become nursing
      professional after graduation. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results
      of the study may be referenced by nursing educators, nursing administrators, and
      nursing policy makers.

PMID- 27026562
TI  - [Exploring the Primary Adaptation Process of First-Ever Stroke Patients].
AB  - BACKGROUND: Stroke is a leading cause of death worldwide and the third leading
      cause of disease-related mortality in Taiwan. Furthermore, stroke is a major
      cause of functional disability in adults, causing physiological, psychological,
      and social impacts. Little qualitative research has been conducted on the primary
      adaptation process of patients with first-ever stroke in Taiwan. PURPOSE: The
      present study explored the primary adaptation process of patients with first-ever
      stroke. METHODS: This qualitative study used purposive sampling to enroll 12
      patients with first-ever stroke for interviews, followed by theoretical sampling.
      Grounded theory guided the methodology and data analysis. Data analysis was
      performed simultaneously in accordance with the coding process. RESULTS: The
      primary adaptation process used by the participants involved the two main
      categories of "impacts of stroke" and "adaptation after stroke", with three
      subcategories associated, respectively, with the former (loss of physical
      autonomy, diminishing perceptions of self-value, and stroke-related hardships
      turning into social isolation) and with the latter (regaining autonomy after
      rehabilitation, receiving support from family without being a burden, and release
      from suffering/becoming more positive). The core category that emerged from the
      present study was: "Facing stroke, hoping for the best, transforming lives."
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The above findings on the primary
      adaptation process of stroke patients provide an important reference for clinical
      nurses/healthcare professionals who have responsibilities to care for patients
      with first-ever stroke. In addition, healthcare professionals should offer more
      health education and psychological support to stroke patients based on individual
      patient needs.

PMID- 27026563
TI  - [Mindfulness: A Concept Analysis].
AB  - "Mindfulness" is an emerging concept in the field of healthcare. Ranging from
      stress relief to psychotherapy, mindfulness has been confirmed to be an effective
      tool to help individuals manage depression, anxiety, obsessive-compulsive
      disorder, and other health problems in clinical settings. Scholars currently use
      various definitions for mindfulness. While some of these definitions overlap,
      significant differences remain and a general scholarly consensus has yet to be
      reached. Several domestic and international studies have explored mindfulness
      related interventions and their effectiveness. However, the majority of these
      studies have focused on the fields of clinical medicine, consultation, and
      education. Mindfulness has rarely been applied in clinical nursing practice and
      no related systematic concept analysis has been conducted. This paper conducts a
      concept analysis of mindfulness using the concept analysis method proposed by
      Walker and Avant (2011). We describe the defining characteristics of mindfulness,
      clarify the concept, and confirm the predisposing factors and effects of
      mindfulness using examples of typical cases, borderline cases, related cases, and
      contrary case. Findings may provide nursing staff with an understanding of the
      concept of mindfulness for use in clinical practice in order to help patients
      achieve a comfortable state of body and mind healing. 

PMID- 27026564
TI  - [Nursing Care of Lumbar Spine Fusion Surgery Using a Semi-Rigid Device (ISOBAR)].
AB  - Aging frequently induces degenerative changes in the spine. Patients who suffer
      from lumbar degenerative disease tend to have lower back pain, neurological
      claudication, and neuropathy. Furthermore, incontinence may be an increasing
      issue as symptoms become severe. Lumbar spine fusion surgery is necessary if
      clinical symptoms continue to worsen or if the patient fails to respond to
      medication, physical therapy, or alternative treatments. However, this surgical
      procedure frequently induces adjacent segment disease (ASD), which is evidenced
      by the appearance of pathological changes in the upper and lower sections of the
      spinal surgical sites. In 1997, ISOBAR TTL dynamic rod stabilization was
      developed for application in spinal fusion surgery to prevent ASD-related
      complications. The device has proven effective in reducing pain in the lower back
      and legs, decreasing functional disability, improving quality of life, and
      retarding disc degeneration. However, the effectiveness of this intervention in
      decreasing the incidence of ASD requires further research investigation, and
      relevant literature and research in Taiwan is still lacking. This article
      discusses lumbar degenerative disease, its indications, the contraindications of
      lumbar spine fusion surgery using ISOBAR, and related postoperative nursing care.
      We hope this article provides proper and new knowledge to clinical nurses for the
      care of patients undergoing lumbar spine fusion surgery with ISOBAR. 

PMID- 27026565
TI  - [The Nutritional Care Experience of a Post-Operative Periampullary Cancer Patient
      With Cachexia].
AB  - Cachexia is one of the most widely overlooked of the syndromes that are
      experienced by cancer patients. This syndrome is especially prevalent among
      patients with gastroenterology tract cancer. Although the National Comprehensive
      Cancer Network (NCCN) issued palliative-care practice guidelines for cachexia in
      2015, guidelines have yet to be issued for the clinical setting. The authors
      reviewed the literature and applied their clinical experience to create an
      approach for identifying the degree of cachexia in a post-operative patient with
      periampullary cancer. This approach assesses the nutritional status, physical
      status, laboratory results, and gastrointestinal system functions of the patient
      using the Cachexia Assessment Scale (CAS) and NCCN Practice Guidelines for
      Cachexia. The patient improved under nursing care with an increase in nutritional
      intake and physical activity facilitating their process of post-surgical physical
      recovery. The authors hope that this experience using the combined CAS-NCCN
      Practice Guidelines will help clinical caregivers better understand how to apply
      the relevant guidelines in clinical settings. The developed approach may help
      nurses assess the comprehensive nutrition status of patients and related factors
      in order to provide interventions that will decrease the progression of cachexia
      effectively and promote quality of life. 

PMID- 27026566
TI  - Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune
      mediated responses and survival benefits.
AB  - New therapies for melanoma have yielded promising results, but their application
      is limited because of serious side-effects and only moderate impact on patient
      survival. Vaccine therapies may offer some hope by targeting tumor-specific
      responses, considering the immunogenic nature of melanomas. To investigate the
      safety profile and efficiency of a xenogeneic cell-based vaccine therapy in stage
      III melanoma patients and evaluate the survival rate in treated patients. Twenty
      seven stage III melanoma patients were immunized with a lyophilized xenogeneic
      polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC
      cells. Neither grade III/IV toxicities, nor clinically significant changes in
      blood and biochemical parameters were noted after an induction course of 10 XPV
      subcutaneous immunizations. No laboratory or clinical signs of systemic
      autoimmunity were documented. Following 10 vaccinations, a relative increase in
      the numbers of circulating memory CD4+CD45RO+ T cells (but not CD8+ CD45RO+ T
      cells) was observed. Peripheral blood mononuclear cells obtained from XPV-treated
      patients demonstrated increased proliferative responses to human BRO melanoma
      associated antigens and marked increases in serum levels of IFN-gamma and IL-8.
      Serum levels of TNF-alpha, IL-4 and IL-6 were not affected. The overall five-year
      survival rate in the treated patients was significantly higher than that in 27
      control patients with matched clinical and prognostic characteristics (55% vs
      18%). XPV-based immunotherapy could be maximally effective when started as early
      as possible before or after surgical excision of the primary tumor and local
      metastases, i.e. when tumor-mediated suppressive effects on immunity are minimal.

PMID- 27026567
TI  - Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced
      perfusion MRI predicts survival in recurrent glioblastoma treated with
      bevacizumab.
AB  - BACKGROUND AND PURPOSE: In glioblastoma, tumor progression appears to be
      triggered by expression of VEGF, a regulator of blood vessel permeability.
      Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing
      circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which
      does not always correlate with treatment response. Our objectives were: (1) to
      evaluate whether changes in DSC perfusion MRI-derived leakage could predict
      survival in recurrent glioblastoma, and (2) to estimate whether leakage at
      baseline was related to treatment outcome. MATERIALS AND METHODS: We
      retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated
      with bevacizumab as second line chemotherapy. Leakage at baseline and changes in
      maximum leakage between baseline and the first follow-up after treatment were
      selected for quantitative analysis. Survival univariate analysis was made
      constructing survival curves using Kaplan-Meier method and comparing subgroups by
      log rank probability test. RESULTS: Leakage reduction at 8 weeks after initiation
      of bevacizumab treatment had a significant influence on overall survival (OS) and
      progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer
      for patients with leakage reduction at the first follow-up. Higher leakage at
      baseline was associated with leakage reduction after treatment. Odds ratio of
      treatment response was 9 for patients with maximum leakage at baseline >5.
      CONCLUSIONS: Leakage decrease may predict OS and PFS in recurrent glioblastomas
      treated with bevacizumab. Leakage reduction postulates as a potential biomarker
      for treatment response evaluation. Leakage at baseline seems to predict response
      to treatment, but was not independently associated with survival.

PMID- 27026569
TI  - [Optic glioma and Lisch nodules in a 4 year-old with neurofibromatosis type 1].

PMID- 27026568
TI  - Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux
      disease and in esophageal adenocarcinoma.
AB  - BACKGROUND: Clinically useful marker molecules for the progression of
      gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal
      adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory
      conditions exhibit increased expression of ADAMs, 'a disintegrin and
      metalloproteinases'. METHODS: We assessed the expression of five ADAMs (9, 10,
      12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and
      Western blotting, and in human samples of normal esophagus, esophagitis, BE,
      Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by
      immunohistochemistry. RESULTS: EAC patients showed increased mRNA expression of
      ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9
      and ADAM10 proteins were increased in EAC. Patient samples also showed increased
      mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and
      19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed
      increased ADAM9 mRNA. CONCLUSIONS: ADAM9 expression is increased in EAC. Its
      predecessors show increased ADAM9 mRNA expression. The importance of the
      alterations in ADAM expression for the development of EAC, and their use as
      marker molecules, warrant further studies.

PMID- 27026570
TI  - Ambulatory blood pressure reduction following high-intensity interval exercise
      performed in water or dryland condition.
AB  - We aimed to compare blood pressure (BP) responses following moderate-intensity
      continuous exercise (MICE), high-intensity interval exercise (HIIE) in dry land
      or HIIE in immersed condition, using 24-hour ambulatory BP monitoring. Forty-two
      individuals (65 +/- 7 years, 52% men) with a baseline BP >= 130/85 mm Hg
      (systolic/diastolic blood pressures [SBP/DBP]) were randomly assigned to perform
      one of the three following exercises on a stationary cycle: MICE (24 minutes at
      50% peak power output) or HIIE in dry land (two sets of 10 minutes with phases of
      15 seconds 100% peak power output interspersed by 15 seconds of passive recovery)
      or HIIE in up-to-the-chest immersed condition. While MICE modified none of the 24
      hour average hemodynamic variables, dryland HIIE induced a 24-hour BP decrease
      (SBP: -3.6 +/- 5.7/DBP: -2.8 +/- 3.0 mm Hg, P < .05) and, to a much greater
      extent, immersed HIIE (SBP: -6.8 +/- 9.5/DBP: -3.0 +/- 4.5 mm Hg, P < .05). The
      one condition that modified 24-hour pulse-wave velocity was immersed HIIE (-0.21
      +/- 0.30 m/s, P < .05).

PMID- 27026571
TI  - Utility of ambulatory blood pressure monitoring in the evaluation of elevated
      clinic blood pressures in children.
AB  - Although ambulatory blood pressure monitoring (ABPM) is recognized for its role
      in assessing white coat hypertension, other uses include evaluation of treatment
      adequacy, nocturnal hypertension, dipping status, and hypertension severity. We
      performed a retrospective study of ABPMs completed at a single center from
      November 2007 to October 2011 to determine the frequency of white coat
      hypertension, prehypertension, and hypertension in children and the correlation
      of these findings with office BPs. A total of 247 ABPMs were performed in 206
      children, ages 4-20 years, including 48 recordings in 39 diabetic patients and 64
      recordings in treated hypertensive patients. We found a poor correlation between
      hypertensive status based on clinic BP and diagnosis on ABPM, and evidence for a
      white coat effect. Among treated patients, ABPM results resulted in medication
      changes in 63%. We conclude that ABPM is a useful tool for characterizing
      hypertensive status and treatment adequacy in children.

PMID- 27026572
TI  - Tertiary syphilis: tubero-serpiginous and tubero-ulcerous syphilids.

PMID- 27026573
TI  - ASAH1 variant causing a mild SMA phenotype with no myoclonic epilepsy: a
      clinical, biochemical and molecular study.
AB  - ASAH1 gene encodes for acid ceramidase that is involved in the degradation of
      ceramide into sphingosine and free fatty acids within lysosomes. ASAH1 variants
      cause both the severe and early-onset Farber disease and rare cases of spinal
      muscular atrophy (SMA) with progressive myoclonic epilepsy (SMA-PME),
      phenotypically characterized by childhood onset of proximal muscle weakness and
      atrophy due to spinal motor neuron degeneration followed by occurrence of severe
      and intractable myoclonic seizures and death in the teenage years. We studied two
      subjects, a 30-year-old pregnant woman and her 17-year-old sister, affected with
      a very slowly progressive non-5q SMA since childhood. No history of seizures or
      myoclonus has been reported and EEG was unremarkable. The molecular study of
      ASAH1 gene showed the presence of the homozygote nucleotide variation c.124A>G
      (r.124a>g) that causes the amino acid substitution p.Thr42Ala. Biochemical
      evaluation of cultured fibroblasts showed both reduction in ceramidase activity
      and accumulation of ceramide compared with the normal control. This study
      describes for the first time the association between ASAH1 variants and an adult
      SMA phenotype with no myoclonic epilepsy nor death in early age, thus expanding
      the phenotypic spectrum of ASAH1-related SMA. ASAH1 molecular analysis should be
      considered in the diagnostic testing of non-5q adult SMA patients.

PMID- 27026574
TI  - Leveraging a high resolution microfluidic assay reveals insights into pathogenic
      fungal spore germination.
AB  - Germination of spores into actively growing cells is a process essential for
      survival and pathogenesis of many microbes. Molecular mechanisms governing
      germination, however, are poorly understood in part because few tools exist for
      evaluating and interrogating the process. Here, we introduce an assay that
      leverages developments in microfluidic technology and image processing to
      quantitatively measure germination with unprecedented resolution, assessing both
      individual cells and the population as a whole. Using spores from Cryptococcus
      neoformans, a leading cause of fatal fungal disease in humans, we developed a
      platform to evaluate spores as they undergo morphological changes during
      differentiation into vegetatively growing yeast. The assay uses pipet-accessible
      microdevices that can be arrayed for efficient testing of diverse
      microenvironmental variables, including temperature and nutrients. We discovered
      that temperature influences germination rate, a carbon source alone is sufficient
      to induce germination, and the addition of a nitrogen source sustains it. Using
      this information, we optimized the assay for use with fungal growth inhibitors to
      pinpoint stages of germination inhibition. Unexpectedly, the clinical antifungal
      drugs amphotericin B and fluconazole did not significantly alter the process or
      timing of the transition from spore to yeast, indicating that vegetative growth
      and germination are distinct processes in C. neoformans. Finally, we used the
      high temporal resolution of the assay to determine the precise defect in a slow
      germination mutant. Combining advances in microfluidics with a robust fungal
      molecular genetic system allowed us to identify and alter key temporal,
      morphological, and molecular events that occur during fungal germination.

PMID- 27026575
TI  - Numerical Approach for the Assessment of Pressure Generated by Elastic
      Compression Bandage.
AB  - Compression of the lower leg by bandages is a common treatment for the advanced
      stages of some venous or lymphatic pathologies. The outcomes of this treatment
      directly result from the pressure generated onto the limb. Various bandage
      configurations are proposed by manufacturers: the study of these configurations
      requires the development of reliable methods to predict pressure distribution
      applied by compression bandages. Currently, clinicians and manufacturers have no
      dedicated tools to predict bandage pressure generation. A numerical simulation
      approach is presented in this work, which includes patient-specific leg geometry
      and bandage. This model provides the complete pressure distribution over the leg.
      The results were compared to experimental pressure measurements and pressure
      values computed with Laplace's law. Using an appropriate surrogate model, this
      study demonstrated that such simulation is appropriate to account for phenomena
      which are neglected in Laplace's law, like geometry changes due to bandage
      application.

PMID- 27026576
TI  - Changes in the salivary microbiota of oral leukoplakia and oral cancer.

PMID- 27026578
TI  - Ineffective Leadership.
AB  - Radiology leaders can have a profound impact on the success and working
      environment of a radiology department, promoting core values and inspiring staff
      members to achieve the organization's mission. On the other hand, ineffective
      leaders can have a devastating effect on a radiology department by impairing
      communication among members, undermining staff commitment to the organization's
      success, and stifling the development of other staff members and leaders in the
      organization. One of the most important investments a radiology department can
      make is in identifying, cultivating, and promoting new leaders. The authors
      describe 13 habits and characteristics of new leaders that lead these individuals
      to address situations in both ineffective and counterproductive ways, impeding
      the performance of a radiology department and its capacity to play a meaningful
      role in shaping the future of radiology. New leaders must continually learn and
      improve their leadership skills if they are to avoid the destructive habits of
      ineffective leaders and successfully overcome the challenges facing radiology
      today. Senior leaders may also benefit from understanding the pitfalls that make
      leaders ineffective and should strive to continually improve their leadership
      skills given the critical role of leadership in the success of radiology
      departments. 

PMID- 27026577
TI  - Travel Burden to Breast MRI and Utilization: Are Risk and Sociodemographics
      Related?
AB  - PURPOSE: Mammography, unlike MRI, is relatively geographically accessible.
      Additional travel time is often required to access breast MRI. However, the
      amount of additional travel time and whether it varies on the basis of
      sociodemographic or breast cancer risk factors is unknown. METHODS: The
      investigators examined screening mammography and MRI between 2005 and 2012 in the
      Breast Cancer Surveillance Consortium by (1) travel time to the closest and
      actual mammography facility used and the difference between the two, (2) women's
      breast cancer risk factors, and (3) sociodemographic characteristics. Logistic
      regression was used to examine the odds of traveling farther than the closest
      facility in relation to women's characteristics. RESULTS: Among 821,683 screening
      mammographic examinations, 76.6% occurred at the closest facility, compared with
      51.9% of screening MRI studies (n = 3,687). The median differential travel time
      among women not using the closest facility for mammography was 14 min
      (interquartile range, 8-25 min) versus 20 min (interquartile range, 11-40 min)
      for breast MRI. Differential travel time for both imaging modalities did not vary
      notably by breast cancer risk factors but was significantly longer for nonurban
      residents. For non-Hispanic black compared with non-Hispanic white women, the
      adjusted odds of traveling farther than the closest facility were 9% lower for
      mammography (odds ratio, 0.91; 95% confidence interval, 0.87-0.95) but more than
      two times higher for MRI (odds ratio, 2.64; 95% confidence interval, 1.36-5.13).
      CONCLUSIONS: Breast cancer risk factors were not related to excess travel time
      for screening MRI, but sociodemographic factors were, suggesting the possibility
      that geographic distribution of advanced imaging may exacerbated disparities for
      some vulnerable populations.

PMID- 27026579
TI  - State of Integration Between PACS and Other IT Systems: A National Survey of
      Academic Radiology Departments.
AB  - PURPOSE: The aim of this study was to investigate the state of integration
      between PACS and other IT systems relevant to radiologists' routine work across
      US academic radiology departments (ARDs). The results were intended to assess
      readiness for the ongoing transition to value-based health care by providing
      insights into currently challenging areas of integration but also areas
      associated with high levels of anticipated workflow efficiency improvements.
      METHODS: A cross-sectional survey was conducted using an online survey approved
      by the Society of Chairs of Academic Radiology Departments and sent to its
      members. Collected responses were analyzed with descriptive statistics and
      Fisher's exact tests. RESULTS: The response rate was 26% (34 of 132 members), and
      the respondents covered a large spectrum of ARDs considering location, size
      aspects, year of PACS introduction, and filmless production. Most notable
      findings included widespread high-level integration of PACS with dictation
      systems (>90%), low penetration of integration between PACS and critical
      notification systems (15%), and an overall better integration of PACS and
      radiology information systems (82%) than of PACS and electronic medical records
      (47%). CONCLUSIONS: Integration supporting radiologists' personal productivity is
      well spread among US ARDs, but as we transition into a value-based health care
      delivery model, there is a need to focus further integration efforts on systems
      with the greatest potential to document value in a patient-centric setting.
      Examples of such focus areas include integration of PACS and electronic medical
      records, adoption of vendor-neutral archives, and the use of workflow management
      systems.

PMID- 27026580
TI  - Association Between Facility Type During Pediatric Inpatient Rehabilitation and
      Functional Outcomes.
AB  - OBJECTIVE: To compare functional outcomes between children receiving inpatient
      rehabilitation at children's hospitals and those at other facilities. DESIGN:
      Retrospective cohort study. SETTING: Inpatient rehabilitation facilities.
      PARTICIPANTS: Children (N=28,793) aged 6 months to 18 years who received initial
      inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Total, cognitive, and motor developmental functional quotients (DFQs; which is
      the WeeFIM score divided by age-adjusted norms and multiplied by 100) at
      discharge from inpatient rehabilitation and WeeFIM efficiency (the change in
      WeeFIM score from admission to discharge divided by the length of the
      rehabilitation stay), adjusting for age, sex, race, insurance, region, admission
      function, impairment type, discharge year, and length of stay. RESULTS: A total
      of 12,732 children received rehabilitation at 25 children's hospitals and 16,061
      at 36 other facilities (general hospitals or freestanding rehabilitation
      hospitals). Adjusting for clustering by facility, patients at children's
      hospitals had a lower cognitive DFQ at admission (difference between children's
      hospitals and other facility types, -3.8; 95% confidence interval [CI], -7.7 to 
      0.1), a shorter length of stay (median, 16d vs 22d; P<.001), and a higher WeeFIM
      efficiency (difference, 0.63; 95% CI, 0.25-1.00) than did children at other
      facility types. Rehabilitation in a children's hospital was independently
      associated with a higher discharge cognitive DFQ (regression coefficient, 2.3;
      95% CI, 0.3-4.2) and more efficient rehabilitation admissions (regression
      coefficient, 0.3; 95% CI, 0.1-0.6). CONCLUSIONS: Children who receive inpatient
      rehabilitation at children's hospitals have more efficient inpatient
      rehabilitation admissions, a shorter median length of stay, and a slight
      improvement in cognitive function than do children at other facility types.

PMID- 27026581
TI  - Reactive oxygen species are involved in insulin-dependent regulation of autophagy
      in primary rat podocytes.
AB  - Autophagy is an intracellular defense mechanism responsible for the turnover of
      damaged or non-functional cellular constituents. This process provides cells with
      energy and essential compounds under unfavorable environmental conditions-such as
      oxidative stress and hyperglycemia, which are both observed in diabetes. The most
      common diabetes complication is diabetic nephropathy (DN), which can lead to
      renal failure. This condition often includes impaired podocyte function. Here we
      investigated autophagic activity in rat podocytes cultured with a high insulin
      concentration (300nM). Autophagy was activated after 60min of insulin
      stimulation. Moreover, this effect was abolished following pharmacological
      (apocynin) or genetic (siRNA) inhibition of NAD(P)H oxidase activity, indicating
      that insulin-dependent autophagy stimulation involved reactive oxygen species
      (ROS). We also observed a continuous and time-dependent increase of podocyte
      albumin permeability in response to insulin, and this process was slightly
      improved by autophagy inhibition following short-term insulin exposure. Our
      results suggest that insulin may be a factor affecting the development of
      diabetic nephropathy.

PMID- 27026582
TI  - Erythroid activator NF-E2, TAL1 and KLF1 play roles in forming the LCR HSs in the
      human adult beta-globin locus.
AB  - The beta-like globin genes are developmental stage specifically transcribed in
      erythroid cells. The transcription of the beta-like globin genes requires
      erythroid specific activators such as GATA-1, NF-E2, TAL1 and KLF1. However, the
      roles of these activators have not fully elucidated in transcription of the human
      adult beta-globin gene. Here we employed hybrid MEL cells (MEL/ch11) where a
      human chromosome containing the beta-globin locus is present and the adult beta
      globin gene is highly transcribed by induction. The roles of erythroid specific
      activators were analyzed by inhibiting the expression of NF-E2, TAL1 or KLF1 in
      MEL/ch11 cells. The loss of each activator decreased the transcription of human
      beta-globin gene, locus wide histone hyperacetylation and the binding of other
      erythroid specific activators including GATA-1, even though not affecting the
      expression of other activators. Notably, sensitivity to DNase I was reduced in
      the locus control region (LCR) hypersensitive sites (HSs) with the depletion of
      activators. These results indicate that NF-E2, TAL1 and KLF1, all activators play
      a primary role in HSs formation in the LCR. It might contribute to the
      transcription of human adult beta-globin gene by allowing the access of
      activators and cofactors. The roles of activators in the adult beta-globin locus
      appear to be different from the roles in the early fetal locus.

PMID- 27026583
TI  - Challenges to prevent secondary fractures in patients with hip fractures in
      Joetsu Myoko, Japan through the increased use of osteoporosis treatment and
      collaboration with family doctors.
AB  - The Niigata Prefectural Central Hospital (NPCH) is one of the main hospitals for
      the cities of Joetsu and Myoko, Niigata Prefecture, Japan, an area with a
      population of 240,141, of whom 26.7 % were aged >=65 years in 2009. In the NPCH,
      patients with hip fractures are admitted to an orthopedic ward within 4 h, 89.2 %
      of patients are operated on within 48 h during working hours, and the prevalence
      of pressure ulcers is 1.5 %. To reduce the incidence of hip fractures, two major
      challenges emphasizing secondary fracture prevention were initiated in 2012. The
      first challenge used a team approach-hospital pharmacists asked patients about
      their drug use histories, orthopedic surgeons began drug therapy for osteoporosis
      after explaining to patients its importance for the prevention of secondary hip
      fractures, nurses assessed the risk of falling, and physiotherapists conducted
      rehabilitation with the aim of preventing falls. The second challenge focused on
      maintaining treatment for osteoporosis after discharge, when patients were under
      the oversight of family doctors. The percentages of patients with primary hip
      fractures who were taking anti-osteoporosis medications at the time of discharge
      in 2009, 2012, 2013 and 2014 were 21, 33, 41, and 43 %, respectively. The 12
      month incidences of hip fractures on the unaffected side in 2009, 2012, 2013 and
      2014 were 7.4, 2.2, 0, and 2.4 %, respectively, and the 24-month incidences of
      such fractures in 2009, 2012 and 2013 were 12, 7.6, and 5.2 %, respectively. Our
      challenges were effective at decreasing the incidence of secondary fractures.

PMID- 27026585
TI  - Picosecond laser ultrasonics for imaging of transparent polycrystalline materials
      compressed to megabar pressures.
AB  - Picosecond laser ultrasonics is an all-optical experimental technique based on
      ultrafast high repetition rate lasers applied for the generation and detection of
      nanometric in length coherent acoustic pulses. In optically transparent materials
      these pulses can be detected not only on their arrival at the sample surfaces but
      also all along their propagation path inside the sample providing opportunity for
      imaging of the sample material spatial inhomogeneities traversed by the acoustic
      pulse. Application of this imaging technique to polycrystalline elastically
      anisotropic transparent materials subject to high pressures in a diamond anvil
      cell reveals their significant texturing/structuring at the spatial scales
      exceeding dimensions of the individual crystallites.

PMID- 27026584
TI  - Appropriate prescribing in nursing homes demonstration project (APDP) study
      protocol: pragmatic, cluster-randomized trial and mixed methods process
      evaluation of an Ontario policy-maker initiative to improve appropriate
      prescribing of antipsychotics.
AB  - BACKGROUND: Antipsychotic medications are routinely prescribed in nursing homes
      to address the behavioral and psychological symptoms of dementia. Unfortunately,
      inappropriate prescribing of antipsychotic medications is common and associated
      with increased morbidity, adverse drug events, and hospitalizations. Multifaceted
      interventions can achieve a 12-20 % reduction in antipsychotic prescribing levels
      in nursing homes. Effective interventions have featured educational outreach and
      ongoing performance feedback. METHODS/DESIGN: This pragmatic, cluster-randomized
      control trial and embedded process evaluation seeks to determine the effect of
      adding academic detailing to audit and feedback on prescribing of antipsychotic
      medications in nursing homes, compared with audit and feedback alone. Nursing
      homes within pre-determined regions of Ontario, Canada, are eligible if they
      express an interest in the intervention. The academic detailing intervention will
      be delivered by registered health professionals following an intensive training
      program including relevant clinical issues and techniques to support health
      professional behavior change. Physicians in both groups will have the opportunity
      to access confidential reports summarizing their prescribing patterns for
      antipsychotics in comparison to the local and provincial average. Participating
      homes will be allocated to one of the two arms of the study (active/full
      intervention versus standard audit and feedback) in two waves, with a 2:1
      allocation ratio. Homes will be randomized after stratifying for geography,
      baseline antipsychotic prescription rates, and size, to ensure a balance of
      characteristics. The primary outcome is antipsychotic dispensing in nursing
      homes, measured 6 months after allocation; secondary outcomes include clinical
      outcomes and healthcare utilization. DISCUSSION: Policy-makers and the public
      have taken note that antipsychotics are used in nursing homes in Ontario far more
      than other jurisdictions. Academic detailing can be an effective technique to
      address challenges in appropriate prescribing in nursing homes, but effect sizes
      vary widely. This opportunistic, policy-driven evaluation, embedded within a
      government-initiated demonstration project, was designed to ensure policy-makers
      receive the best evidence possible regarding whether and how to scale up the
      intervention. TRIAL REGISTRATION: ClinicalTrials.gov NLM Identifier: NCT02604056
      .

PMID- 27026586
TI  - Current status of medical radiation exposure in Korea - recent efforts to develop
      a radiation exposure control system focussed on justification and optimisation.
AB  - Radiation exposure from diagnostic medical imaging has increased in Korea.
      Radiological societies play a key role in radiation safety issues in Korea,
      including guidelines, accreditation, advocacy, scientific activity, and
      education. Any medical radiation exposure must be justified, and examinations
      using ionising radiation must be optimised. Education of referring physicians and
      radiologists is also important for justification. Medical physicists and
      radiographers have an important role to play in quality management and
      optimisation. Regulations are essential to control medical radiation exposure.
      Therefore, national organisations have made a significant effort to regulate and
      monitor medical radiation exposure using guidelines, accreditation, and even the
      law. Medical radiation exposure must be controlled, and this could be achieved by
      continuous interest from health professionals and organisations. 

PMID- 27026588
TI  - Controllable self-assembly of a novel Bi2MoO6-based hybrid photocatalyst:
      excellent photocatalytic activity under UV, visible and near-infrared
      irradiation.
AB  - Herein, using a simple one-step method, a Bi2MoO6-based photocatalyst with novel
      ultrathin nanohollow structure and simultaneous sub-10 nm Bi nanoparticles and
      sub-1 nm graphitic nitrogen-doped carbon nanodot (NCD) modification were
      successfully obtained. The coordination impact of the novel structure, SPR effect
      of Bi nanoparticles, up-conversion performance of graphitic NCDs and cooperative
      electronic capture properties of Bi metal and NCDs make the hybrid simultaneously
      exhibit fast charge separation and broad spectrum photocatalytic activity under
      UV, visible and near-infrared irradiation, leading to excellent photooxidation
      and photoreduction performance. 

PMID- 27026587
TI  - Asthma in Urban Children: Epidemiology, Environmental Risk Factors, and the
      Public Health Domain.
AB  - Asthma is the most commonly reported chronic condition of childhood in developed
      countries, with 6.5 million children affected in the USA. A disparate burden of
      childhood asthma is seen among socioeconomically disadvantaged youth, often
      concentrated in urban areas with high poverty rates. Host factors that predispose
      a child to asthma include atopy, male gender, parental history of asthma, and
      also race, ethnicity, and genetic and epigenetic susceptibilities. Environmental
      factors, such as improved hygiene, ambient air pollution, and early life
      exposures to microbes and aeroallergens, also influence the development of
      asthma. With greater than 90% of time spent indoors, home exposures (such as
      cockroach, rodent, and indoor air pollution) are highly relevant for urban
      asthma. Morbidity reduction may require focused public health initiatives for
      environmental intervention in high priority risk groups and the addition of
      immune modulatory agents in children with poorly controlled disease.

PMID- 27026589
TI  - The value of decision tree analysis in planning anaesthetic care in obstetrics.
AB  - The use of decision tree analysis is discussed in the context of the anaesthetic
      and obstetric management of a young pregnant woman with joint hypermobility
      syndrome with a history of insensitivity to local anaesthesia and a previous
      difficult intubation due to a tongue tumour. The multidisciplinary clinical
      decision process resulted in the woman being delivered without complication by
      elective caesarean section under general anaesthesia after an awake fibreoptic
      intubation. The decision process used is reviewed and compared retrospectively to
      a decision tree analytical approach. The benefits and limitations of using
      decision tree analysis are reviewed and its application in obstetric anaesthesia
      is discussed. 

PMID- 27026590
TI  - Analysis of genetics and risk factors of Alzheimer's Disease.
AB  - Alzheimer's Disease is the leading neurodegenerative cause of dementia. The
      pathogenesis is not clearly understood yet, is believed to be the complex
      interaction between genetic and environmental factors. Consequently vascular risk
      factors and Apolipoprotein E genotyping are increasingly gaining importance. This
      study aimed at assessing the relationships between Alzheimer's Disease and
      Apolipoprotein E phenotype and vascular risk factors. Patients diagnosed with
      "possible Alzheimer's Disease" in the Gazi University, Department of Neurology,
      were included in the study and age-matched volunteer patients who attended the
      polyclinic were included as a control group. In this study, the risk factors
      including low education level, smoking, hyperlipidemia, higher serum total
      cholesterol levels, and hyperhomocysteinemia were found to be statistically
      significantly more common in the Alzheimer's Disease group in comparison to the
      Control Group, while all Apolipoprotein E epsilon4/epsilon4 genotypes were found
      in the Alzheimer's Disease group. The presence of the Apolipoprotein E epsilon4
      allele is believed to increase vascular risk factors as well as to affect
      Alzheimer's Disease directly. The biological indicators which are used in
      identifying the patients' genes will be probably used in the treatment plan of
      the patients in the future.

PMID- 27026591
TI  - Hydrogen sulfide prevents Abeta-induced neuronal apoptosis by attenuating
      mitochondrial translocation of PTEN.
AB  - Neuronal cell apoptosis is an important pathological change in Alzheimer's
      disease (AD). Hydrogen sulfide (H(2)S) is known to be a novel gaseous signaling
      molecule and a cytoprotectant in many diseases including AD. However, the
      molecular mechanism of the antiapoptosis activity of H(2)S in AD is not yet fully
      understood. The aim of the present study is to evaluate the inhibitory effects of
      H(2)S on Abeta (Abeta)-induced apoptosis and the molecular mechanisms underlying
      primary neuron cells. Our results showed that sodium hydrosulfide (NaHS), a donor
      of H(2)S, significantly ameliorated Abeta-induced cell apoptosis. NaHS also
      reversed the Abeta-induced translocation of the phosphatase and tensin homologs
      deleted on chromosome 10 (PTEN) from the cytosol to the mitochondria.
      Furthermore, H(2)S increased the level of p-AKT/AKT significantly. Interestingly,
      the antiapoptosis effects of H(2)S were blocked down by specific PI3K/AKT
      inhibitor wortmannin. In conclusion, these data indicate that H(2)S inhibits
      Abeta-induced neuronal apoptosis by attenuating mitochondrial translocation of
      PTEN and that activation of PI3K/AKT signaling pathway plays a critical role in
      H(2)S-mediated neuronal protection. Our findings provide a novel route into the
      molecular mechanisms of neuronal apoptosis in AD.

PMID- 27026593
TI  - Cre recombinase expression or topical tamoxifen treatment do not affect retinal
      structure and function, neuronal vulnerability or glial reactivity in the mouse
      eye.
AB  - Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression
      are frequently used research tools to allow the conditional deletion of target
      genes via the Cre-loxP system. Here we analyzed for the first time in a
      comprehensive and comparative way, whether retinal Cre expression or topical
      tamoxifen treatment itself would cause structural or functional changes,
      including changes in the expression profiles of molecular markers, glial
      reactivity and photoreceptor vulnerability. To this end, we characterized the
      transgenic alpha-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreERTM mouse
      lines, all having robust Cre expression in the neuronal retina. In addition, we
      characterized the effects of topical tamoxifen treatment itself in wildtype mice.
      We performed morphometric analyses, immunohistochemical staining, in vivo ERG and
      angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of
      Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was
      studied by using light damage as a model for photoreceptor degeneration. Taken
      together, neither the expression of Cre, nor topical tamoxifen treatment caused
      detectable changes in retinal structure and function, the expression profiles of
      investigated molecular markers, glial reactivity and photoreceptor vulnerability.
      We conclude that the Cre-loxP system and its induction through tamoxifen is a
      safe and reliable method to delete desired target genes in the neural retina.

PMID- 27026592
TI  - Opposing actions of the synapse-associated protein of 97-kDa molecular weight
      (SAP97) and Disrupted in Schizophrenia 1 (DISC1) on Wnt/beta-catenin signaling.
AB  - It has been suggested that synapse-associated protein of 97-kDa molecular weight
      (SAP97) is a susceptibility factor for childhood and adult neuropsychiatric
      disorders. SAP97 is a scaffolding protein that shares direct and indirect binding
      partners with the Disrupted in Schizophrenia 1 (DISC1) gene product, a gene with
      strong association with neuropsychiatric disorders. Here we investigated the
      possibility that these two proteins converge upon a common molecular pathway.
      Since DISC1 modifies Wnt/beta-catenin signaling via changes in glycogen synthase
      kinase 3 beta (GSK3beta) phosphorylation, we asked if SAP97 impacts Wnt/beta
      catenin signaling and GSK3beta phosphorylation. We find that SAP97 acts as
      inhibitor of Wnt signaling activity and can suppress the stimulatory effects of
      DISC1 on beta-catenin transcriptional activity. Reductions in SAP97 abundance
      also decrease GSK3beta phosphorylation. In addition, we find that over expression
      of DISC1 leads to an increase in the abundance of SAP97, by inhibiting its
      proteasomal degradation. Our findings suggest that SAP97 and DISC1 contribute to
      maintaining Wnt/beta-catenin signaling activity within a homeostatic range by
      regulating GSK3beta phosphorylation.

PMID- 27026595
TI  - High-performance integrated field-effect transistor-based sensors.
AB  - Field-effect transistors (FETs) have succeeded in modern electronics in an era of
      computers and hand-held applications. Currently, considerable attention has been
      paid to direct electrical measurements, which work by monitoring changes in
      intrinsic electrical properties. Further, FET-based sensing systems drastically
      reduce cost, are compatible with CMOS technology, and ease down-stream
      applications. Current technologies for sensing applications rely on time
      consuming strategies and processes and can only be performed under recommended
      conditions. To overcome these obstacles, an overview is presented here in which
      we specifically focus on high-performance FET-based sensor integration with nano
      sized materials, which requires understanding the interaction of surface
      materials with the surrounding environment. Therefore, we present strategies,
      material depositions, device structures and other characteristics involved in FET
      based devices. Special attention was given to silicon and polyaniline nanowires
      and graphene, which have attracted much interest due to their remarkable
      properties in sensing applications. 

PMID- 27026596
TI  - Evaluation of the availability of bound analyte for passive sampling in the
      presence of mobile binding matrix.
AB  - Elucidating the availability of the bound analytes for the mass transfer through
      the diffusion boundary layers (DBLs) adjacent to passive samplers is important
      for understanding the passive sampling kinetics in complex samples, in which the
      lability factor of the bound analyte in the DBL is an important parameter. In
      this study, the mathematical expression of lability factor was deduced by
      assuming a pseudo-steady state during passive sampling, and the equation
      indicated that the lability factor was equal to the ratio of normalized
      concentration gradients between the bound and free analytes. Through the
      introduction of the mathematical expression of lability factor, the modified
      effective average diffusion coefficient was proven to be more suitable for
      describing the passive sampling kinetics in the presence of mobile binding
      matrixes. Thereafter, the lability factors of the bound polycyclic aromatic
      hydrocarbons (PAHs) with sodium dodecylsulphate (SDS) micelles as the binding
      matrixes were figured out according to the improved theory. The lability factors
      were observed to decrease with larger binding ratios and smaller micelle sizes,
      and were successfully used to predict the mass transfer efficiencies of PAHs
      through DBLs. This study would promote the understanding of the availability of
      bound analytes for passive sampling based on the theoretical improvements and
      experimental assessments. 

PMID- 27026594
TI  - Peri-infarct depolarizations during focal ischemia in the awake Spontaneously
      Hypertensive Rat. Minimizing anesthesia confounds in experimental stroke.
AB  - Anesthesia profoundly impacts peri-infarct depolarizations (PIDs), but only one
      prior report has described their monitoring during experimental stroke in awake
      animals. Since temporal patterns of PID occurrence are model specific, the
      current study examined PID incidence during focal ischemia in the awake
      Spontaneously Hypertensive Rat (SHR), and documented the impact of both prior and
      concurrent isoflurane anesthesia. For awake recordings, electrodes were implanted
      under isoflurane anesthesia 1day to 5weeks prior to occlusion surgery. Rats were
      then subjected to permanent or transient (2h) tandem occlusion of the middle
      cerebral and ipsilateral common carotid arteries, followed by PID monitoring for
      up to 3days. Comparison perfusion imaging studies evaluated PID-associated
      hyperemic transients during permanent ischemia under anesthesia at varied
      intervals following prior isoflurane exposure. Prior anesthesia attenuated PID
      number at intervals up to 1week, establishing 2weeks as a practical recovery
      duration following surgical preparation to avoid isoflurane preconditioning
      effects. PIDs in awake SHR were limited to the first 4h after permanent
      occlusions. Maintaining anesthesia during this interval reduced PID number, and
      prolonged their occurrence through several hours following anesthesia
      termination. Although PID number otherwise correlated with infarct size, PID
      suppression by anesthesia was not protective in the absence of reperfusion. PIDs
      persisted up to 36h after transient occlusions. These results differ markedly
      from the one previous report of such monitoring in awake Sprague-Dawley rats,
      which found an extended biphasic PID time course during 24h after both permanent
      and transient filament occlusions. PID occurrence closely reflects the time
      course of infarct progression in the respective models, and may be more useful
      than absolute PID number as an index of ongoing pathology.

PMID- 27026597
TI  - A novel miniaturized zinc oxide/hydroxylated multiwalled carbon nanotubes as a
      stir-brush microextractor device for carbamate pesticides analysis.
AB  - A novel miniaturized "stir-brush microextractor" was prepared using a zinc
      oxide/hydroxylated multiwalled carbon nanotubes (ZnO/MWCNTs-OH) coated stainless
      steel brush connected to a small dc motor. The synthesized zinc oxide on each
      strand of stainless steel had a flower-like nanostructure when observed by a
      scanning electron microscope (SEM). This structure produced a large surface area
      before it was coated with the hydroxylated multiwalled carbon nanotubes sorbent.
      Under optimal conditions, the developed device provided a good linearity for the
      extraction of carbofuran and carbaryl, in the range of 25-500 ng mL(-1) and 50
      500 ng mL(-1), respectively, with low limits of detection of 17.5 +/- 2.0 ng mL(
      1) and 13.0 +/- 1.8 ng mL(-1). It also provided a good stir-brush-to-stir-brush
      reproducibility (% relative standard deviation < 5.6%, n = 6). The device was
      applied for the extraction and preconcentration of carbamate pesticides in fruit
      and vegetable samples prior to analysis with a gas chromatograph coupled with a
      flame ionization detector (GC-FID). Carbofuran was found at 9.24 +/- 0.93 ng g(
      1) and carbaryl was detected at 7.05 +/- 0.61 ng g(-1) with good recoveries in
      the range of 73.7 +/- 10.0% to 108.4 +/- 2.6% for carbofuran and 75.7 +/- 10.0%
      to 111.7 +/- 5.7% for carbaryl. 

PMID- 27026598
TI  - Solid-phase extraction based on ground methacrylate monolith modified with gold
      nanoparticles for isolation of proteins.
AB  - In this study, a novel polymeric material functionalized with gold nanoparticles
      (AuNPs) was prepared as solid-phase extraction (SPE) sorbent for isolation of
      proteins. The sorbent was synthesized from a powdered poly(glycidyl-co-ethylene
      dimethacrylate) monolith, and modified with ammonia, followed by immobilization
      of AuNPs on the pore surface of the material. To evaluate the performance of this
      SPE support, proteins were selected as test solutes, being the extraction
      conditions and other parameters (loading capacity and regenerative ability of
      sorbent) established. The results indicated that this sorbent could be employed
      to selectively capture proteins according to their pI, on the basis of the strong
      affinity of these biomacromolecules towards to AuNPs surface. The applicability
      of this sorbent was demonstrated by isolating protein species of interest (bovine
      serum albumin, cytochrome c and lectins in European mistletoe leaves), followed
      by SDS-PAGE analysis. 

PMID- 27026599
TI  - Tandem air-agitated liquid-liquid microextraction as an efficient method for
      determination of acidic drugs in complicated matrices.
AB  - A rapid and simple microextraction method with a high sample clean-up, termed as
      tandem air-agitated liquid-liquid microextraction (TAALLME), is described. This
      method is based upon the tandem implementation of the air-agitated liquid-liquid
      microextraction (AALLME), and this approach improves the applicability of the
      dispersive liquid-liquid microextraction (DLLME) methods in complicated matrices.
      With very simple tools, the three non-steroidal anti-inflammatory drugs
      diclofenac, ibuprofen, and mefenamic acid were efficiently extracted, with an
      overall extraction time of 7 min. By performing the first AALLME, these acidic
      analytes, contained in an aqueous sample solution (donor phase, 8.0 mL), were
      extracted into the organic solvent (1,2-dichloroethane, 37 MUL), and their simple
      back-extraction into the aqueous acceptor solution (pH, 10.01, 51 MUL) was
      obtained in 2 min by a second implementation of AALLME. Response surface
      methodology (RSM) was used for optimization of the experimental parameters. The
      pH values 2.94 and 10.01 were obtained for the donor and acceptor phases,
      respectively, and the volumes 99.5 and 51 MUL were obtained for the organic
      solvent and the acceptor phase, respectively, as the optimal extraction
      conditions. Under the optimized conditions, tandem AALLME-HPLC-UV provided a good
      linearity in the range of 0.5-4000 ng mL(-1), limits of detection (0.1-0.3 ng mL(
      1)), extraction repeatabilities (relative standard deviations (RSDs) below 7.7%,
      n = 5), and the enrichment factors (EFs) of 80-104. Finally, the applicability of
      the proposed method was evaluated by the extraction and determination of the
      drugs under study in the wastewater and human plasma samples. 

PMID- 27026600
TI  - Computational optimization of the configuration of a spatially resolved
      spectroscopy sensor for milk analysis.
AB  - A global optimizer has been developed, capable of computing the optimal
      configuration in a probe for spatially resolved reflectance spectroscopy (SRS).
      The main objective is to minimize the number of detection fibers, while
      maintaining an accurate estimation of both absorption and scattering profiles.
      Multiple fibers are necessary to robustify the estimation of optical properties
      against noise, which is typically present in the measured signals and influences
      the accuracy of the inverse estimation. The optimizer is based on a robust
      metamodel-based inverse estimation of the absorption coefficient and a reduced
      scattering coefficient from the acquired SRS signals. A genetic algorithm is used
      to evaluate the effect of the fiber placement on the performance of the inverse
      estimator to find the bulk optical properties of raw milk. The algorithm to find
      the optimal fiber placement was repeatedly executed for cases with a different
      number of detection fibers, ranging from 3 to 30. Afterwards, the optimal designs
      for each considered number of fibers were compared based on their performance in
      separating the absorption and scattering properties, and the significance of the
      differences was tested. A sensor configuration with 13 detection fibers was found
      to be the combination with the lowest number of fibers which provided an
      estimation performance which was not significantly worse than the one obtained
      with the best design (30 detection fibers). This design resulted in the root mean
      squared error of prediction (RMSEP) of 1.411 cm(-1) (R(2) = 0.965) for the
      estimation of the bulk absorption coefficient values, and 0.382 cm(-1) (R(2) =
      0.996) for the reduced scattering coefficient values. 

PMID- 27026601
TI  - FRET-based modified graphene quantum dots for direct trypsin quantification in
      urine.
AB  - A versatile nanoprobe was developed for trypsin quantification with fluorescence
      resonance energy transfer (FRET). Here, fluorescence graphene quantum dot is
      utilized as a donor while a well-designed coumarin derivative, CMR2, as an
      acceptor. Moreover, bovine serum albumin (BSA), as a protein model, is not only
      served as a linker for the FRET pair, but also a fluorescence enhancer of the
      quantum dots and CMR2. In the presence of trypsin, the FRET system would be
      destroyed when the BSA is digested by trypsin. Thus, the emission peak of the
      donor is regenerated and the ratio of emission peak of donor/emission peak of
      acceptor increased. By the ratiometric measurement of these two emission peaks,
      trypsin content could be determined. The detection limit of trypsin was found to
      be 0.7 MUg/mL, which is 0.008-fold of the average trypsin level in acute
      pancreatitis patient's urine suggesting a high potential for fast and low cost
      clinical screening. 

PMID- 27026602
TI  - A novel fluorescent aptasensor based on silica nanoparticles, PicoGreen and
      exonuclease III as a signal amplification method for ultrasensitive detection of
      myoglobin.
AB  - Measurement of myoglobin (Mb) in human blood serum is of great interest for quick
      diagnosis of acute myocardial infarction (AMI). In this study, a novel
      fluorescent aptasensor was designed for ultrasensitive and selective detection of
      Mb, based on target-induced high fluorescence intensity, complementary strand of
      aptamer (CS), PicoGreen (PG) dye, exonuclease III (Exo III) and silica
      nanoparticles coated with streptavidin (SNPs-Streptavidin). The developed
      aptasensor obtains characteristics of SNPs as enhancers of fluorescence
      intensity, Exo III as an enzyme which selectively digests the 3'-end of double
      stranded DNA (dsDNA), PG as a fluorescent dye which could selectively bind to
      dsDNA and high selectivity and sensitivity of aptamer (Apt) toward its target. In
      the absence of Mb, no free CS remains in the environment of SNPs-Streptavidin,
      resulting in a weak fluorescence emission. In the present of Mb, dsDNA-modified
      SNPs-Streptavidin complex forms, leading to a very strong fluorescence emission.
      The developed fluorescent aptasensor exhibited high specificity toward Mb with a
      limit of detection (LOD) as low as 52 pM. In addition, the designed fluorescent
      aptasensor was efficiently used to detect Mb in human serum. 

PMID- 27026603
TI  - A novel immunochromatographic assay based on a time-resolved chemiluminescence
      strategy for the multiplexed detection of ractopamine and clenbuterol.
AB  - A novel multiplexed immunochromatographic assay (ICA) based on a time-resolved
      chemiluminescence (CL) strategy was developed for quantitative detection of beta
      agonists, by utilizing ractopamine (RAC) and clenbuterol (CLE) as the models.
      Different from conventional multiplexed ICA methods which usually require two or
      more test lines, this strategy was developed for detection of two beta-agonists
      by using only one test line on the nitrocellulose membrane. In this study,
      horseradish peroxidase and alkaline phosphatase were used as the signal probes to
      label RAC antibody and CLE antibody, respectively. The two CL reactions with
      flash type and glow type kinetics characteristics were triggered simultaneously
      by injecting the coreactants, then the signals for RAC and CLE detections were
      recorded at 3 s and 300 s after coreactants injection, respectively. Owing to the
      utilization of CL detection, this protocol showed ideal sensitivity for
      quantitation. Under the optimal conditions, the detection limits for RAC and CLE
      were 0.17 ng mL(-1) and 0.067 ng mL(-1) (S/N = 3), respectively. The whole assay
      process can be accomplished within 20 min without complicated sample
      pretreatment. The proposed method was successfully applied for the detection of
      RAC and CLE in spiked swine urine. It opens up a new pathway for designing a low
      cost, time-efficiency and multiplexed strategy for rapid screening and field
      assay. 

PMID- 27026604
TI  - Identification of catecholamine neurotransmitters using fluorescence sensor
      array.
AB  - A nano-based sensor array has been developed for identification and
      discrimination of catecholamine neurotransmitters based on optical properties of
      their oxidation products under alkaline conditions. To produce distinct
      fluorescence response patterns for individual catecholamine, quenching of
      thioglycolic acid functionalized cadmium telluride (CdTe) quantum dots, by
      oxidation products, were employed along with the variation of fluorescence
      spectra of oxidation products. The spectral changes were analyzed with
      hierarchical cluster analysis (HCA) and principal component analysis (PCA) to
      identify catecholamine patterns. The proposed sensor could efficiently
      discriminate the individual catecholamine (i.e., dopamine, norepinephrine, and l
      DOPA) and their mixtures in the concentration range of 0.25-30 MUmol L(-1).
      Finally, we found that the sensor had capability to identify the various
      catecholamines in urine sample. 

PMID- 27026605
TI  - Development of a sandwiched microarray platform for studying the interactions of
      antibiotics with Staphylococcus aureus.
AB  - It still confronts an outstanding challenge to screen efficient antibacterial
      drugs from millions of potential antibiotic candidates. In this regard, a
      sandwiched microarray platform has been developed to culture live bacteria and
      carry out high-throughput screening antibacterial drugs. The optimized lectin
      hydrogel microarray can be used as an efficient bacterial capturing and culturing
      platform, which is beneficial to identify spots and collect data. At the same
      time, a matching drug-laden polyacrylamide microarray with Luria-Bertani (LB)
      culture medium can be generated automatically and accurately by using a standard
      non-contacting procedure. A large number of microscale culture chambers (more
      than 100 individual samples) between two microarrays can be formed by linking two
      aligned hydrogel spots using LB culture medium, where live bacteria can be co
      cultured with drug candidates. Using Staphylococcus aureus (S. aureus) and four
      well-known antibiotics (amoxicillin, vancomycin, streptomycin and
      chloramphenicol) as model system, the MIC (minimum inhibitory concentration)
      values of the antibiotics can be determined by the drug induced change of
      bacterial growth, and the results demonstrate that the MIC values of amoxicillin,
      vancomycin and streptomycin are 1.7 MUg mL(-1), 3.3 MUg mL(-1) and 10.3 MUg mL(
      1), respectively. 

PMID- 27026606
TI  - Graphene-based field effect transistor in two-dimensional paper networks.
AB  - We demonstrate the fabrication of a graphene-based field effect transistor (GFET)
      incorporated in a two-dimensional paper network format (2DPNs). Paper serves as
      both a gate dielectric and an easy-to-fabricate vessel for holding the solution
      with the target molecules in question. The choice of paper enables a simpler
      alternative approach to the construction of a GFET device. The fabricated device
      is shown to behave similarly to a solution-gated GFET device with electron and
      hole mobilities of ~1256 cm(2) V(-1) s(-1) and ~2298 cm(2) V(-1) s(-1)
      respectively and a Dirac point around ~1 V. When using solutions of ssDNA and
      glucose it was found that the added molecules induce negative electrolytic gating
      effects shifting the conductance minimum to the right, concurrent with increasing
      carrier concentrations which results to an observed increase in current response
      correlated to the concentration of the solution used. 

PMID- 27026607
TI  - Fabrication of highly sensitive and selective nanocomposite film based on
      CuNPs/fullerene-C60/MWCNTs: An electrochemical nanosensor for trace recognition
      of paracetamol.
AB  - Designing an electrochemical sensor for versatile clinical applications is a
      sophisticated task and how dedicatedly functionalized composite materials can
      perform on this stage is a challenge for today and tomorrow's Nanoscience and
      Nanotechnology. In the present work, we demonstrate a new strategy for the
      development of novel electrochemical sensor based on catalytic nanocomposite
      film. Fullerene-C60 and multi-walled carbon nanotubes (MWCNTs) were dropped on
      the pre-treated carbon paste electrode (CPE) and copper nanoparticles (CuNPs)
      electrochemically deposited on the modified CPE to form nanocomposite film of
      CuNPs/C60/MWCNTs/CPE. In this work, an electrochemical method based on square
      wave voltammetry (SWV) employing CuNPs/C60/MWCNTs/CPE has been presented for the
      recognition and determination of paracetamol (PT). Developed electrochemical
      sensor was characterized using cyclic voltammetry (CV), electrochemical impedance
      spectroscopy (EIS), and chronocoulometry. The composite film made the fabricated
      sensor to display high sensitivity and good selectivity for PT detection. The
      influence of the optimization parameters such as pH, accumulation time,
      deposition potential, scan rate and effect of loading of composite mixture of C60
      MWCNTs and CuNPs on the electrochemical performance of the sensor were evaluated.
      A linear range from 4.0 * 10(-9) to 4.0 * 10(-7) M for PT detection was obtained
      with a detection limit of 7.3 * 10(-11) M. The fabricated sensor was successfully
      applied to the detection of PT in biological samples with good recovery ranging
      from 99.21 to 103%. 

PMID- 27026608
TI  - Application of pH-responsive poly(2-dimethyl-aminoethylmethacrylate)-block
      poly(acrylic acid) coatings for the open-tubular capillary electrochromatographic
      analysis of acidic and basic compounds.
AB  - A new type of stimuli-responsive polymeric (SRP) coating has been prepared for
      use in open tubular capillary electrochromatography (OT-CEC), by grafting poly(2
      dimethylaminoethylmethacrylate)-block-poly(acrylic acid) (PDMAEMA-b-PAA) as a Y
      shaped block copolymer with two dissimilar chain compositions onto the inner
      walls of aminopropyl-modified silica capillaries. The grafting process introduced
      weakly charged functional groups from the PAA and PDMAEMA, enabling the
      generation of electroendosmotic flow with magnitude and direction adjustable by
      changing the pH of the running buffer electrolyte. This stimuli-responsive
      PDMAEMA-b-PAA block copolymer was found to provide excellent resolution of
      various acidic and basic compounds, leading to efficient analyte separation. When
      operated in the OT-CEC mode, separation selectivities could be readily
      manipulated via differential contributions from chromatographic and
      electrophoretic mechanisms, simply by changing the pH or the ionic strength of
      the running buffer electrolyte. 

PMID- 27026609
TI  - Two- and three-dimensional co-culture models of soft tissue healing: pericyte
      endothelial cell interaction.
AB  - The demographic change in western countries towards an older population is being
      shadowed by an increased appearance of chronic diseases influencing soft tissue
      healing in a negative manner. Although various promising therapeutic approaches
      are available for treating chronic wounds, no in vitro model exists that
      successfully allows the analysis of interacting cells and of the effect of
      therapeutic drugs within a wound. Granulation tissue assures wound stability, neo
      angiogenesis and revascularization finally leading to functional soft tissue
      repair. As one of the first steps in developing a model for human granulation
      tissue, we examined microvascular endothelial cells and pericytes in conventional
      2D and in 3D spheroid co-cultures. We determined which parameters could be used
      in a standardized manner and whether the cultures were responsive to hypoxia and
      to erythropoietin supplementation. The read-out parameters of cell migration,
      cell density, rate of apoptotic cells, spatial cell distribution in the spheroid
      and spheroid volume were shown to be excellent analytic measures. In addition,
      quantification of hypoxia-related genes identified a total of 13 genes that were
      up-regulated in spheroids after hypoxia. As these parameters delivered reliable
      results in the present approach and as the general morphological distribution of
      pericytes and endothelial cells within the spheroid occurred in a typical manner,
      we believe that this basic in vitro model will serve for the future study of
      diverse aspects of soft tissue healing.

PMID- 27026610
TI  - A network-based drug repositioning infrastructure for precision cancer medicine
      through targeting significantly mutated genes in the human cancer genomes.
AB  - OBJECTIVE: Development of computational approaches and tools to effectively
      integrate multidomain data is urgently needed for the development of newly
      targeted cancer therapeutics. METHODS: We proposed an integrative network-based
      infrastructure to identify new druggable targets and anticancer indications for
      existing drugs through targeting significantly mutated genes (SMGs) discovered in
      the human cancer genomes. The underlying assumption is that a drug would have a
      high potential for anticancer indication if its up-/down-regulated genes from the
      Connectivity Map tended to be SMGs or their neighbors in the human protein
      interaction network. RESULTS: We assembled and curated 693 SMGs in 29 cancer
      types and found 121 proteins currently targeted by known anticancer or noncancer
      (repurposed) drugs. We found that the approved or experimental cancer drugs could
      potentially target these SMGs in 33.3% of the mutated cancer samples, and this
      number increased to 68.0% by drug repositioning through surveying exome
      sequencing data in approximately 5000 normal-tumor pairs from The Cancer Genome
      Atlas. Furthermore, we identified 284 potential new indications connecting 28
      cancer types and 48 existing drugs (adjusted P < .05), with a 66.7% success rate
      validated by literature data. Several existing drugs (e.g., niclosamide, valproic
      acid, captopril, and resveratrol) were predicted to have potential indications
      for multiple cancer types. Finally, we used integrative analysis to showcase a
      potential mechanism-of-action for resveratrol in breast and lung cancer treatment
      whereby it targets several SMGs (ARNTL, ASPM, CTTN, EIF4G1, FOXP1, and STIP1).
      CONCLUSIONS: In summary, we demonstrated that our integrative network-based
      infrastructure is a promising strategy to identify potential druggable targets
      and uncover new indications for existing drugs to speed up molecularly targeted
      cancer therapeutics.

PMID- 27026611
TI  - Discharge recommendation based on a novel technique of homeostatic analysis.
AB  - OBJECTIVE: We propose a computational framework for integrating diverse patient
      measurements into an aggregate health score and applying it to patient stability
      prediction. MATERIALS AND METHODS: We mapped retrospective patient data from the
      Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) II clinical
      database into a discrete multidimensional space, which was searched for
      measurement combinations and trends relevant to patient outcomes of interest.
      Patient trajectories through this space were then used to make outcome
      predictions. As a case study, we built AutoTriage, a patient stability prediction
      tool to be used for discharge recommendation. RESULTS: AutoTriage correctly
      identified 3 times as many stabilizing patients as existing tools and achieved an
      accuracy of 92.9% (95% CI: 91.6-93.9%), while maintaining 94.5% specificity.
      Analysis of AutoTriage parameters revealed that interdependencies between risk
      factors comprised the majority of each patient stability score. DISCUSSION:
      AutoTriage demonstrated an improvement in the sensitivity of existing stability
      prediction tools, while considering patient safety upon discharge. The relative
      contributions of risk factors indicated that time-series trends and measurement
      interdependencies are most important to stability prediction. CONCLUSION: Our
      results motivate the application of multidimensional analysis to other clinical
      problems and highlight the importance of risk factor trends and interdependencies
      in outcome prediction.

PMID- 27026612
TI  - Pragmatic precision oncology: the secondary uses of clinical tumor molecular
      profiling.
AB  - BACKGROUND: Precision oncology increasingly utilizes molecular profiling of
      tumors to determine treatment decisions with targeted therapeutics. The molecular
      profiling data is valuable in the treatment of individual patients as well as for
      multiple secondary uses. OBJECTIVE: To automatically parse, categorize, and
      aggregate clinical molecular profile data generated during cancer care as well as
      use this data to address multiple secondary use cases. METHODS: A system to
      parse, categorize and aggregate molecular profile data was created. A nayve
      Bayesian classifier categorized results according to clinical groups. The
      accuracy of these systems were validated against a published expertly-curated
      subset of molecular profiling data. RESULTS: Following one year of operation, 819
      samples have been accurately parsed and categorized to generate a data repository
      of 10,620 genetic variants. The database has been used for operational, clinical
      trial, and discovery science research. CONCLUSIONS: A real-time database of
      molecular profiling data is a pragmatic solution to several knowledge management
      problems in the practice and science of precision oncology.

PMID- 27026613
TI  - Enteric disease episodes and the risk of acquiring a future sexually transmitted
      infection: a prediction model in Montreal residents.
AB  - OBJECTIVE: The sexual transmission of enteric diseases poses an important public
      health challenge. We aimed to build a prediction model capable of identifying
      individuals with a reported enteric disease who could be at risk of acquiring
      future sexually transmitted infections (STIs). MATERIALS AND METHODS: Passive
      surveillance data on Montreal residents with at least 1 enteric disease report
      was used to construct the prediction model. Cases were defined as all subjects
      with at least 1 STI report following their initial enteric disease episode. A
      final logistic regression prediction model was chosen using forward stepwise
      selection. RESULTS: The prediction model with the greatest validity included age,
      sex, residential location, number of STI episodes experienced prior to the first
      enteric disease episode, type of enteric disease acquired, and an interaction
      term between age and male sex. This model had an area under the curve of 0.77 and
      had acceptable calibration. DISCUSSION: A coordinated public health response to
      the sexual transmission of enteric diseases requires that a distinction be made
      between cases of enteric diseases transmitted through sexual activity from those
      transmitted through contaminated food or water. A prediction model can aid public
      health officials in identifying individuals who may have a higher risk of
      sexually acquiring a reportable disease. Once identified, these individuals could
      receive specialized intervention to prevent future infection. CONCLUSION: The
      information produced from a prediction model capable of identifying higher risk
      individuals can be used to guide efforts in investigating and controlling
      reported cases of enteric diseases and STIs.

PMID- 27026614
TI  - Patients, care partners, and shared access to the patient portal: online
      practices at an integrated health system.
AB  - OBJECTIVE: To describe the characteristics and online practices of patients and
      "care partners" who share explicit access to a patient portal account at a large
      integrated health system that implemented shared access functionality in 2003.
      MATERIALS AND METHODS: Survey of 323 patients and 389 care partners at Geisinger
      Health System with linked information regarding access and use of patient portal
      functionality. RESULTS: Few (0.4%) registered adult patient portal users shared
      access to their account. Patients varied in age (range: 18-102); more than half
      had a high school education or less (53.6%). Patient motivations for sharing
      access included: to help manage care (41.9%), for emergency reasons (29.7%), lack
      of technology experience (18.4%), or care partner request (10.0%). Care partners
      were parents (39.8%), adult children (27.9%), spouses (26.2%), and other
      relatives (6.1%). Patients were more likely than care partners to have inadequate
      health literacy (54.8% versus 8.8%, P < .001) and less confident in their ability
      to manage their care (53.0% versus 88.1%; P < .001). Care partners were more
      likely than patients to perform health management activities electronically
      (95.5% versus 48.4%; P < .001), access the patient portal (89.2% versus 30.3%; P
      < .001), and use patient portal functionality such as secure messaging (39.6%
      versus 13.9%; P < .001). Care partners used their own credentials (89.1%) and
      patient credentials (23.3%) to access the patient portal. DISCUSSION AND
      CONCLUSION: Shared access is an underused strategy that may bridge patients'
      health literacy deficits and lack of technology experience and that helps but
      does not fully resolve concerns regarding patient and care partner identity
      credentials.

PMID- 27026615
TI  - PheKB: a catalog and workflow for creating electronic phenotype algorithms for
      transportability.
AB  - OBJECTIVE: Health care generated data have become an important source for
      clinical and genomic research. Often, investigators create and iteratively refine
      phenotype algorithms to achieve high positive predictive values (PPVs) or
      sensitivity, thereby identifying valid cases and controls. These algorithms
      achieve the greatest utility when validated and shared by multiple health care
      systems.Materials and Methods We report the current status and impact of the
      Phenotype KnowledgeBase (PheKB, http://phekb.org), an online environment
      supporting the workflow of building, sharing, and validating electronic phenotype
      algorithms. We analyze the most frequent components used in algorithms and their
      performance at authoring institutions and secondary implementation sites.
      RESULTS: As of June 2015, PheKB contained 30 finalized phenotype algorithms and
      62 algorithms in development spanning a range of traits and diseases. Phenotypes
      have had over 3500 unique views in a 6-month period and have been reused by other
      institutions. International Classification of Disease codes were the most
      frequently used component, followed by medications and natural language
      processing. Among algorithms with published performance data, the median PPV was
      nearly identical when evaluated at the authoring institutions (n = 44; case
      96.0%, control 100%) compared to implementation sites (n = 40; case 97.5%,
      control 100%). DISCUSSION: These results demonstrate that a broad range of
      algorithms to mine electronic health record data from different health systems
      can be developed with high PPV, and algorithms developed at one site are
      generally transportable to others. CONCLUSION: By providing a central repository,
      PheKB enables improved development, transportability, and validity of algorithms
      for research-grade phenotypes using health care generated data.

PMID- 27026616
TI  - Analysis of clinical decision support system malfunctions: a case series and
      survey.
AB  - OBJECTIVE: To illustrate ways in which clinical decision support systems (CDSSs)
      malfunction and identify patterns of such malfunctions. MATERIALS AND METHODS: We
      identified and investigated several CDSS malfunctions at Brigham and Women's
      Hospital and present them as a case series. We also conducted a preliminary
      survey of Chief Medical Information Officers to assess the frequency of such
      malfunctions. RESULTS: We identified four CDSS malfunctions at Brigham and
      Women's Hospital: (1) an alert for monitoring thyroid function in patients
      receiving amiodarone stopped working when an internal identifier for amiodarone
      was changed in another system; (2) an alert for lead screening for children
      stopped working when the rule was inadvertently edited; (3) a software upgrade of
      the electronic health record software caused numerous spurious alerts to fire;
      and (4) a malfunction in an external drug classification system caused an alert
      to inappropriately suggest antiplatelet drugs, such as aspirin, for patients
      already taking one. We found that 93% of the Chief Medical Information Officers
      who responded to our survey had experienced at least one CDSS malfunction, and
      two-thirds experienced malfunctions at least annually. DISCUSSION: CDSS
      malfunctions are widespread and often persist for long periods. The failure of
      alerts to fire is particularly difficult to detect. A range of causes, including
      changes in codes and fields, software upgrades, inadvertent disabling or editing
      of rules, and malfunctions of external systems commonly contribute to CDSS
      malfunctions, and current approaches for preventing and detecting such
      malfunctions are inadequate. CONCLUSION: CDSS malfunctions occur commonly and
      often go undetected. Better methods are needed to prevent and detect these
      malfunctions.

PMID- 27026619
TI  - IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular
      profiles with actionable therapeutics in clinical samples.
AB  - OBJECTIVE: Currently, there is a disconnect between finding a patient's relevant
      molecular profile and predicting actionable therapeutics. Here we develop and
      implement the Integrating Molecular Profiles with Actionable Therapeutics
      (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing
      (WES) to actionable therapeutics. METHODS AND MATERIALS: The IMPACT pipeline
      contains 4 analytical modules: detecting somatic variants, calling copy number
      alterations, predicting drugs against deleterious variants, and analyzing tumor
      heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in
      The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR
      mutations. We also used IMPACT to analyze melanoma patient tumor samples before
      treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor
      treatment. RESULTS: IMPACT Food and Drug Administration (FDA) correctly
      identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT
      linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For
      the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance
      mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a
      novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis
      pipeline predicts these somatic variants to actionable therapeutics. We observed
      the clonal dynamic in the tumor samples after various treatments. We showed that
      IMPACT not only helped in successful prioritization of clinically relevant
      variants but also linked these variations to possible targeted therapies.
      CONCLUSION: IMPACT provides a new bioinformatics strategy to delineate candidate
      somatic variants and actionable therapies. This approach can be applied to other
      patient tumor samples to discover effective drug targets for personalized
      medicine.IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT.

PMID- 27026621
TI  - A multi-center analysis of adverse events among two thousand, three hundred and
      seventy two adult patients undergoing adult autologous stem cell therapy for
      orthopaedic conditions.
AB  - INTRODUCTION: The purpose of the present investigation is to report on detailed
      complications among a much larger group of 2372 orthopaedic patients treated with
      stem cell injections who were followed in a treatment registry for up to nine
      years. METHODS: All patients underwent an MSC-based, percutaneous injection
      treatment of an orthopaedic condition between December 2005 and September 2014 at
      one of 18 clinical facilities. Treated areas of the body included the knee, hip,
      ankle/foot, hand/wrist, elbow, shoulder, and spine. The patients were followed
      prospectively via enrollment in a treatment registry. Patients were followed
      prospectively at one, three, six and 12 months, and annually thereafter, using an
      electronic system, ClinCapture software. RESULTS: A total of 3012 procedures were
      performed on 2372 patients with follow-up period of 2.2 years. A total of 325
      adverse events were reported. The majority were pain post-procedure (n = 93, 3.9
      % of the study population) and pain due to progressive degenerative joint disease
      (n = 90, 3.8 % of the study population). Seven cases reported neoplasms, a lower
      rate than in the general population. The lowest rate of adverse events was
      observed among patients injected with BMC alone. CONCLUSION: Lowest rate of
      adverse events was among those patients receiving BMC injections alone, but the
      higher rate of AEs for BMC plus adipose and cultured cells was readily explained
      by the nature of the therapy or the longer follow-up. There was no clinical
      evidence to suggest that treatment with MSCs of any type in this study increased
      the risk of neoplasm.

PMID- 27026617
TI  - Toward a better understanding of task demands, workload, and performance during
      physician-computer interactions.
AB  - OBJECTIVE: To assess the relationship between (1) task demands and workload, (2)
      task demands and performance, and (3) workload and performance, all during
      physician-computer interactions in a simulated environment. METHODS: Two
      experiments were performed in 2 different electronic medical record (EMR)
      environments: WebCIS (n = 12) and Epic (n = 17). Each participant was instructed
      to complete a set of prespecified tasks on 3 routine clinical EMR-based
      scenarios: urinary tract infection (UTI), pneumonia (PN), and heart failure (HF).
      Task demands were quantified using behavioral responses (click and time
      analysis). At the end of each scenario, subjective workload was measured using
      the NASA-Task-Load Index (NASA-TLX). Physiological workload was measured using
      pupillary dilation and electroencephalography (EEG) data collected throughout the
      scenarios. Performance was quantified based on the maximum severity of omission
      errors. RESULTS: Data analysis indicated that the PN and HF scenarios were
      significantly more demanding than the UTI scenario for participants using WebCIS
      (P < .01), and that the PN scenario was significantly more demanding than the UTI
      and HF scenarios for participants using Epic (P < .01). In both experiments, the
      regression analysis indicated a significant relationship only between task
      demands and performance (P < .01). DISCUSSION: Results suggest that task demands
      as experienced by participants are related to participants' performance. Future
      work may support the notion that task demands could be used as a quality metric
      that is likely representative of performance, and perhaps patient outcomes.
      CONCLUSION: The present study is a reasonable next step in a systematic
      assessment of how task demands and workload are related to performance in EMR
      evolving environments.

PMID- 27026618
TI  - Efficient identification of nationally mandated reportable cancer cases using
      natural language processing and machine learning.
AB  - OBJECTIVE: To help cancer registrars efficiently and accurately identify
      reportable cancer cases. MATERIAL AND METHODS: The Cancer Registry Control Panel
      (CRCP) was developed to detect mentions of reportable cancer cases using a
      pipeline built on the Unstructured Information Management Architecture -
      Asynchronous Scaleout (UIMA-AS) architecture containing the National Library of
      Medicine's UIMA MetaMap annotator as well as a variety of rule-based UIMA
      annotators that primarily act to filter out concepts referring to nonreportable
      cancers. CRCP inspects pathology reports nightly to identify pathology records
      containing relevant cancer concepts and combines this with diagnosis codes from
      the Clinical Electronic Data Warehouse to identify candidate cancer patients
      using supervised machine learning. Cancer mentions are highlighted in all
      candidate clinical notes and then sorted in CRCP's web interface for faster
      validation by cancer registrars. RESULTS: CRCP achieved an accuracy of 0.872 and
      detected reportable cancer cases with a precision of 0.843 and a recall of 0.848.
      CRCP increases throughput by 22.6% over a baseline (manual review) pathology
      report inspection system while achieving a higher precision and recall. Depending
      on registrar time constraints, CRCP can increase recall to 0.939 at the expense
      of precision by incorporating a data source information feature. CONCLUSION: CRCP
      demonstrates accurate results when applying natural language processing features
      to the problem of detecting patients with cases of reportable cancer from
      clinical notes. We show that implementing only a portion of cancer reporting
      rules in the form of regular expressions is sufficient to increase the precision,
      recall, and speed of the detection of reportable cancer cases when combined with
      off-the-shelf information extraction software and machine learning.

PMID- 27026620
TI  - Developing knowledge resources to support precision medicine: principles from the
      Clinical Pharmacogenetics Implementation Consortium (CPIC).
AB  - To move beyond a select few genes/drugs, the successful adoption of
      pharmacogenomics into routine clinical care requires a curated and machine
      readable database of pharmacogenomic knowledge suitable for use in an electronic
      health record (EHR) with clinical decision support (CDS). Recognizing that EHR
      vendors do not yet provide a standard set of CDS functions for pharmacogenetics,
      the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics
      Working Group is developing and systematically incorporating a set of EHR
      agnostic implementation resources into all CPIC guidelines. These resources
      illustrate how to integrate pharmacogenomic test results in clinical information
      systems with CDS to facilitate the use of patient genomic data at the point of
      care. Based on our collective experience creating existing CPIC resources and
      implementing pharmacogenomics at our practice sites, we outline principles to
      define the key features of future knowledge bases and discuss the importance of
      these knowledge resources for pharmacogenomics and ultimately precision medicine.

PMID- 27026624
TI  - Poor nutrition-related policies and practices of global food companies under the
      spotlight.

PMID- 27026622
TI  - Pathoanatomy and computed tomography classification of glenoid fossa fractures
      based on ninety patients.
AB  - PURPOSE: The aim of the article is to present the pathoanatomy and a new
      classification of glenoid fractures developed on the basis of analysis of 3D
      computed tomography (CT) examinations and intra-operative findings. MATERIALS AND
      METHODS: The study group comprised 90 patients (69 men and 21 women) who
      sustained glenoid fractures. Mean patient age was 47 years (17-92). In 77
      nonpolytraumatised patients, anteroposterior (AP) radiographs of the affected
      shoulder girdle were taken, including Neer I and II views. All 90 patients
      underwent CT examination, combined in 73 of them with 3D CT reconstruction
      including subtraction of the humeral head, ribs and clavicle, from the anterior
      and posterolateral views. In total, 52 patients (58 %) were operated on and 38 42
      %) were treated non-operatively. RESULTS: In total, five basic types of injuries
      to the glenoid were identified based on analysis of the separated portion of the
      glenoid fossa: including fractures of the superior glenoid (14 cases, 16 %), the
      anterior glenoid (23 cases, 23 %), the posterior rim of the glenoid (5 cases, 6
      %), the inferior glenoid (38 cases, 42 %) and the entire glenoid (10 cases, 11
      %). CONCLUSION: The proposed classification of glenoid fractures defines five
      basic types of fractures verified by 3D CT reconstructions and intra-operative
      findings. It respects the anatomical architecture of scapula, fracture mechanism,
      associated injuries to the shoulder girdle and, where appropriate, the preferred
      surgical approach.

PMID- 27026626
TI  - Undercounting of football concussions skewed NFL research, US investigation
      alleges.

PMID- 27026627
TI  - Timing of Occurrence Is the Most Important Characteristic of Spot Sign.
AB  - BACKGROUND AND PURPOSE: Most previous studies have used single-phase computed
      tomographic angiography to detect the spot sign, a marker for hematoma expansion
      (HE) in spontaneous intracerebral hemorrhage. We investigated whether defining
      the spot sign based on timing on perfusion computed tomography (CTP) would
      improve its specificity for predicting HE. METHODS: We prospectively enrolled
      supratentorial spontaneous intracerebral hemorrhage patients who underwent CTP
      within 6 hours of onset. Logistic regression was performed to assess the risk
      factors for HE and poor outcome. Predictive performance of individual CTP spot
      sign characteristics were examined with receiver operating characteristic
      analysis. RESULTS: Sixty-two men and 21 women with spontaneous intracerebral
      hemorrhage were included in this analysis. Spot sign was detected in 46% (38/83)
      of patients. Receiver operating characteristic analysis indicated that the timing
      of spot sign occurrence on CTP had the greatest area under receiver operating
      characteristic curve for HE (0.794; 95% confidence interval, 0.630-0.958;
      P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the
      presence of early-occurring spot sign (ie, spot sign before 23.13 seconds) was an
      independent predictor not only of HE (odds ratio=28.835; 95% confidence interval,
      6.960-119.458; P<0.001), but also of mortality at 3 months (odds ratio =22.377;
      95% confidence interval, 1.773-282.334; P=0.016). Moreover, the predictive
      performance showed that the redefined early-occurring spot sign maintained a
      higher specificity for HE compared with spot sign (91% versus 74%). CONCLUSIONS:
      Redefining the spot sign based on timing of contrast leakage on CTP to determine
      early-occurring spot sign improves the specificity for predicting HE and 3-month
      mortality. The use of early-occurring spot sign could improve the selection of
      ICH patients for potential hemostatic therapy.

PMID- 27026628
TI  - RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of
      Lysosomes and Immunoglobulins in Rupture.
AB  - BACKGROUND AND PURPOSE: Analyzing genes involved in development and rupture of
      intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms,
      and identify new treatment strategies. We compared gene expression between
      ruptured and unruptured aneurysms and control intracranial arteries. METHODS: We
      determined expression levels with RNA sequencing. Applying a multivariate
      negative binomial model, we identified genes that were differentially expressed
      between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21
      unruptured aneurysms. The differential expression of 8 relevant and highly
      significant genes was validated using digital polymerase chain reaction. Pathway
      analysis was used to identify enriched pathways. We also analyzed genes with an
      extreme pattern of differential expression: only expressed in 1 condition without
      any expression in the other. RESULTS: We found 229 differentially expressed genes
      in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms.
      The differential expression of all 8 genes selected for digital polymerase chain
      reaction validation was confirmed. Extracellular matrix pathways were enriched in
      aneurysms versus controls, whereas pathways involved in immune response and the
      lysosome pathway were enriched in ruptured versus unruptured aneurysms.
      Immunoglobulin genes were expressed in aneurysms, but showed no expression in
      controls. CONCLUSIONS: For rupture of intracranial aneurysms, we identified the
      lysosome pathway as a new pathway and found further evidence for the role of the
      immune response. Our results also point toward a role for immunoglobulins in the
      pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting
      candidate treatment strategies in the prevention of aneurysm development and
      rupture.

PMID- 27026629
TI  - Imaging Follow-Up of Intracranial Aneurysms Treated by Endovascular Means: Why,
      When, and How?

PMID- 27026630
TI  - Ischemic Stroke Risk in Patients With Atrial Fibrillation and CHA2DS2-VASc Score
      of 1: Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: The CHA2DS2-VASc score aims to improve risk
      stratification of ischemic stroke among patients with atrial fibrillation to
      identify those who can safely forego oral anticoagulation. Oral anticoagulation
      treatment guidelines remain uncertain for CHA2DS2-VASc score of 1. We conducted a
      systematic review and meta-analysis of the risk of ischemic stroke for patients
      with atrial fibrillation and CHA2DS2-VASc score of 0, 1, or 2 not treated with
      oral anticoagulation. METHODS: We searched MEDLINE, Embase, PubMed, Cochrane
      Central Register of Controlled Trials, Cochrane Database of Systematic Reviews,
      and Web of Science from the start of the database up until April 15, 2015. We
      included studies that stratified the risk of ischemic stroke by CHA2DS2-VASc
      score for patients with nonvalvular atrial fibrillation. We estimated the summary
      annual rate of ischemic stroke using random effects meta-analyses and compared
      the estimated stroke rates with published net-benefit thresholds for initiating
      anticoagulants. RESULTS: 1162 abstracts were retrieved, of which 10 met all
      inclusion criteria for the study. There was substantial heterogeneity among
      studies. The summary estimate for the annual risk of ischemic stroke was 1.61%
      (95% confidence interval 0%-3.23%) for CHA2DS2-VASc score of 1, meeting the
      theoretical threshold for using novel oral anticoagulants (0.9%), but below the
      threshold for warfarin (1.7%). The summary incident risk of ischemic stroke was
      0.68% (95% confidence interval 0.12%-1.23%) for CHA2DS2-VASc score of 0 and 2.49%
      (95% confidence interval 1.16%-3.83%) for CHA2DS2-VASc score of 2. CONCLUSIONS:
      Our meta-analysis of ischemic stroke risk in atrial fibrillation patients
      suggests that those with CHA2DS2-VASc score of 1 may be considered for a novel
      oral anticoagulant, but because of high heterogeneity, the decision should be
      based on individual patient characteristics.

PMID- 27026631
TI  - TRAF3 Epigenetic Regulation Is Associated With Vascular Recurrence in Patients
      With Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Clopidogrel is one of the most used antiplatelet drugs in
      patients with cardiovascular disease. However, 16% to 50% of patients have a high
      on-clopidogrel platelet reactivity and an increased risk of ischemic events. The
      pathogenesis of high on-treatment platelet reactivity in patients with stroke is
      only partially explained by genetic variations. This study aims to find
      differentially methylated sites across the genome associated with vascular
      recurrence in ischemic stroke patients treated with clopidogrel. METHODS: From a
      cohort of 1900 patients with ischemic stroke, we selected 42 patients treated
      with clopidogrel, including 21 with a recurrent vascular event and 21 without
      vascular recurrence during the first year of follow-up. Over 480 000 DNA
      methylation sites were analyzed across the genome. Differentially methylated CpG
      sites were identified by nonparametric testing using R. Replication analysis was
      performed in a new cohort of 191 subjects and results were correlated with
      platelet reactivity in a subset of 90 subjects using light transmission
      aggregometry. RESULTS: A total of 73 differentially methylated CpG sites (P<1*10(
      05)) were identified; 3 of them were selected for further replication: cg03548645
      (P=1.42*10(-05), TRAF3), cg09533145 (P=7.81*10(-06), ADAMTS2), and cg15107336
      (P=1.89*10(-05), XRCC1). The cg03548645 CpG remained significant in the
      replication study (P=0.034), a deep analysis of this region revealed another
      methylation site associated with vascular recurrence, P=0.037. Lower cg03548645
      (TRAF3) DNA methylation levels were correlated with an increased platelet
      aggregation (rho=-0.29, P=0.0075). CONCLUSIONS: This study suggests for the first
      time that epigenetics may significantly contribute to the variability of
      clopidogrel response and recurrence of ischemic events in patients with stroke.

PMID- 27026632
TI  - De Novo Aneurysm Formation in Carriers of Saccular Intracranial Aneurysm Disease
      in Eastern Finland.
AB  - BACKGROUND AND PURPOSE: Formation of new (de novo) aneurysms in patients carrying
      saccular intracranial aneurysm (sIA) disease has been published, but data from
      population-based cohorts are scarce. METHODS: Kuopio sIA database
      (http://www.uef.fi/ns) contains all unruptured and ruptured sIA patients admitted
      to Kuopio University Hospital from its Eastern Finnish catchment population. We
      studied the incidence and risk factors for de novo sIA formation in 1419 sIA
      patients with >=5 years of angiographic follow-up, a total follow-up of 18 526
      patient-years. RESULTS: There were 42 patients with a total of 56 de novo sIAs,
      diagnosed in a median of 11.7 years after the first sIA diagnosis. The cumulative
      incidence of de novo sIAs was 0.23% per patient-year and that of subarachnoid
      hemorrhage from a ruptured de novo sIA 0.05% per patient-year. The risk of de
      novo sIA discovery per patient-year increased with younger age at the first sIA
      diagnosis: 2.2% in the patients aged <20 years and 0.46% in the patients aged
      between 20 and 39 years. In Cox regression analysis, smoking history and younger
      age at the first sIA diagnosis significantly associated with de novo sIA
      formation, but female sex, multiple sIAs, and sIA family did not. CONCLUSIONS:
      Patients aged < 40 years at the first sIA diagnosis are in a significant risk of
      developing de novo sIAs, and they should be scheduled for long-term angiographic
      follow-up. Smoking increases the risk of de novo sIA formation, suggesting long
      term follow-up for smokers. Antismoking efforts are highly recommended for sIA
      patients.

PMID- 27026634
TI  - Physical Activity Pattern of Malaysian Preschoolers: Environment, Barriers, and
      Motivators for Active Play.
AB  - Children's physical activity has been correlated with child characteristics and
      social or physical environment. This study aimed to compare preschoolers'
      physical activity among various sociodemographic characteristics and to determine
      barriers, motivators, and environmental factors for active play. A total of 835
      preschoolers were included in this analysis. Time spent on active play, quiet
      play, and screen time was reported by parents. Boys spent significantly more time
      on active play and screen time than girls. Time spent on quiet play was highest
      in East Coast Peninsular Malaysia and lowest in Sarawak. Some 40% of children
      achieved active play recommendation while 27% exceeded daily screen time
      recommendation. Most parents reported that their child played actively in the
      house area; and that the main barrier and motivator to active play were safety
      and child's enjoyment, respectively. These findings demonstrate that
      sociodemographic characteristics and environment should be considered in
      designing physical activity intervention programs.

PMID- 27026635
TI  - Retrospective Evaluation of ASCVD Risk and Statin Therapy Need in Nondiabetic
      Patients Based on the 2013 ACC/AHA Cholesterol Guidelines.
AB  - PURPOSE: Study goal was to assess the impact of the 2013 American College of
      Cardiology and the American Heart Association (ACC/AHA) Cholesterol Guidelines on
      patients in the fourth statin benefit group which included patients aged 40 to 75
      years, without diabetes or clinical atherosclerotic cardiovascular disease
      (ASCVD), and have an ASCVD score >=7.5%. These patients could benefit from
      treatment interventions by a pharmacist. METHODS: Patients were identified from
      electronic health records. A sample of 3503 patients was ascertained from having
      a lipid panel performed within the 12 months before November 1, 2013. Patients
      were excluded if we were unable to calculate 10-year ASCVD risk. RESULTS: A total
      of 3203 patients were included, with 2008 not on statin therapy. Of those, 1507
      (75%) had a 10-year ASCVD risk score <7.5% and 501 (25%) had a score > 7.5%.
      Patient characteristics leading to an increase in risk included advanced age,
      smoker, male, and hypertension treatment. Of 2008 nonstatin patients, there were
      466 (23.2%) who fit criteria for initiation of moderate- or high-intensity
      statin. CONCLUSION: Widespread adoption of the 2013 ACC/AHA Cholesterol
      Guidelines will expand prescribing rates of statins. Implementing screening
      strategies may help identify patients who require treatment in this fourth statin
      benefit group. A pharmacist can be vital in screening patients, educating
      patients regarding the need for medication therapy, and monitoring for adherence
      in these new regimens.

PMID- 27026636
TI  - Recurrent Venous Thromboembolism in Two Patients With Cancer Taking Rivaroxaban.
AB  - Pharmacologic agents for the treatment and prevention of venous thromboembolism
      in the cancer patient population are limited. Currently, low-molecular-weight
      heparin is recommended by national consensus guidelines for this indication.
      Rivaroxaban, an oral factor Xa inhibitor, is Food and Drug Administration (FDA)
      approved for the treatment and prevention of venous thromboembolism and offers
      the convenience of oral fixed-dose regimens, no routine laboratory monitoring,
      and has few drug and dietary interactions; however, its use in patients with
      cancer has not been largely studied. We report 2 cases of recurrent venous
      thromboembolism in patients with active cancer on rivaroxaban therapy. The first
      case is a 64-year-old female admitted for recurrent pulmonary embolism, and the
      second case is a 70-year-old female admitted for recurrent deep vein thrombosis.
      Both patients were receiving rivaroxaban at the time of thromboembolic
      recurrence. These cases serve as a reminder to health-care providers that more
      safety and efficacy data in the cancer patient population are needed prior to
      using rivaroxaban for venous thromboembolism treatment.

PMID- 27026633
TI  - Preclinical studies on the reinforcing effects of cannabinoids. A tribute to the
      scientific research of Dr. Steve Goldberg.
AB  - RATIONALE: The reinforcing effects of most abused drugs have been consistently
      demonstrated and studied in animal models, although those of marijuana were not,
      until the demonstration 15 years ago that delta-9-tetrahydrocannabinol (THC)
      could serve as a reinforcer in self-administration (SA) procedures in squirrel
      monkeys. Until then, those effects were inferred using indirect assessments.
      OBJECTIVES: The aim of this manuscript is to review the primary preclinical
      procedures used to indirectly and directly infer reinforcing effects of
      cannabinoid drugs. METHODS: Results will be reviewed from studies of cannabinoid
      discrimination, intracranial self-stimulation (ICSS), conditioned place
      preference (CPP), as well as change in levels of dopamine assessed in brain areas
      related to reinforcement, and finally from self-administration procedures. For
      each procedure, an evaluation will be made of the predictive validity in
      detecting the potential abuse liability of cannabinoids based on seminal papers,
      with the addition of selected reports from more recent years especially those
      from Dr. Goldberg's research group. RESULTS AND CONCLUSIONS: ICSS and CPP do not
      provide consistent results for the assessment of potential for abuse of
      cannabinoids. However, drug discrimination and neurochemistry procedures appear
      to detect potential for abuse of cannabinoids, as well as several novel "designer
      cannabinoid drugs." Though after 15 years transfer of the self-administration
      model of marijuana abuse from squirrel monkeys to other species remains somewhat
      problematic, studies with the former species have substantially advanced the
      field, and several reports have been published with consistent self
      administration of cannabinoid agonists in rodents.

PMID- 27026637
TI  - Autism spectrum disorder and attention-deficit/hyperactivity disorder in early
      childhood: A review of unique and shared characteristics and developmental
      antecedents.
AB  - Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder
      (ADHD) have overlapping characteristics and etiological factors, but to which
      extent this applies to infant- and preschool age is less well understood.
      Comparing the pathways to ASD and ADHD from the earliest possible stages is
      crucial for understanding how phenotypic overlap emerges and develops.
      Ultimately, these insights may guide preventative and therapeutic interventions.
      Here, we review the literature on the core symptoms, temperament and executive
      function in ASD and ADHD from infancy through preschool age, and draw several
      conclusions: (1) the co-occurrence of ASD and ADHD increases with age, severity
      of symptoms and lower IQ, (2) attention problems form a linking pin between early
      ASD and ADHD, but the behavioral, cognitive and sensory correlates of these
      attention problems partly diverge between the two conditions, (3) ASD and ADHD
      share high levels of negative affect, although the underlying motivational and
      behavioral tendencies seem to differ, and (4) ASD and ADHD share difficulties
      with control and shifting, but partly opposite behaviors seem to be involved.

PMID- 27026638
TI  - Animal behavioral assessments in current research of Parkinson's disease.
AB  - Parkinson's disease (PD), a neurodegenerative disorder, is traditionally
      classified as a movement disorder. Patients typically suffer from many motor
      dysfunctions. Presently, clinicians and scientists recognize that many non-motor
      symptoms are associated with PD. There is an increasing interest in both motor
      and non-motor symptoms in clinical studies on PD patients and laboratory research
      on animal models that imitate the pathophysiologic features and symptoms of PD
      patients. Therefore, appropriate behavioral assessments are extremely crucial for
      correctly understanding the mechanisms of PD and accurately evaluating the
      efficacy and safety of novel therapies. This article systematically reviews the
      behavioral assessments, for both motor and non-motor symptoms, in various animal
      models involved in current PD research. We addressed the strengths and weaknesses
      of these behavioral tests and their appropriate applications. Moreover, we
      discussed potential mechanisms behind these behavioral tests and cautioned
      readers against potential experimental bias. Since most of the behavioral
      assessments currently used for non-motor symptoms are not particularly designed
      for animals with PD, it is of the utmost importance to greatly improve
      experimental design and evaluation in PD research with animal models. Indeed, it
      is essential to develop specific assessments for non-motor symptoms in PD animals
      based on their characteristics. We concluded with a prospective view for
      behavioral assessments with real-time assessment with mobile internet and
      wearable device in future PD research.

PMID- 27026640
TI  - Comparison of Frequency of Bleeding and Major Adverse Cardiac Events After
      Transradial Versus Transfemoral Intervention in the Recent Antiplatelet Era.
AB  - The transradial approach is increasingly used for percutaneous coronary
      intervention (PCI), and we therefore aimed to compare the clinical outcomes after
      transradial intervention (TRI) and transfemoral intervention (TFI) in all
      patients undergoing PCI. Among 6,973 patients enrolled in a nationwide,
      prospective, multicenter registry (February 2013 to September 2013), 1,860
      underwent TRI (n = 1,445, 77.7%) and TFI (n = 415, 22.3%). Bleeding and major
      adverse cardiac events (MACE; death, myocardial infarction, revascularization, or
      stent thrombosis) were compared. Bleeding occurred in 42 patients (2.3%) and was
      significantly less likely in the TRI versus TFI group (overall cohort: 1.5% vs
      4.8%, p = 0.001; propensity score-matched: n = 728, 2.7% vs 5.2%, p = 0.048).
      Multivariate regression revealed that TRI was negatively associated with bleeding
      (odds ratio 0.42, 95% CI 0.21 to 0.83, p = 0.013). MACE occurred in 152 patients
      (8.2%). Kaplan-Meier estimates showed higher MACE-free survival rates in the TRI
      versus TFI group (overall cohort: 93.3% vs 86.7%, log-rank p = 0.026; propensity
      score-matched: 91.8% vs 86.5%, log-rank p = 0.04). Cox proportional analysis
      demonstrated that TRI independently predicted improved MACE (hazard ratio 0.64,
      95% CI 0.43 to 0.91, p = 0.024). In conclusion, TRI is associated with reduced
      bleeding rates and better clinical outcomes than TFI in all patients undergoing
      PCI. 

PMID- 27026641
TI  - Meta-Analysis of the Effectiveness and Safety of Transcatheter Aortic Valve
      Implantation Without Balloon Predilation.
AB  - Evidence regarding the safety and feasibility of transcatheter aortic valve
      implantation without balloon predilation (BP) is scarce. A literature search of
      PubMed, EMBASE, CENTRAL, and major conference proceedings was performed from
      January 2002 to July 2015. There were 18 studies incorporating 2,443 patients
      included in the present study. No differences were observed in the baseline
      characteristics between patients without BP (no-BP) and with BP. Compared with
      BP, no-BP had a shorter procedure time (no-BP vs BP, 124.2 vs 138.8 minutes, p =
      0.008), used less-contrast medium (no-BP vs BP, 126.3 vs 156.3 ml, p = 0.0005)
      and had a higher success rate (odds ratio [OR] 2.24, 95% CI 1.40 to -3.58). In
      addition, no-BP was associated with lower incidences of permanent pacemaker
      implantation (OR 0.45, 95% CI 0.3 to 0.67), grade 2 or greater paravalvular
      leakage (OR 0.55, 95% CI 0.37 to 0.83), and stroke (OR 0.57, 95% CI 0.32 to 1.0).
      Furthermore, no-BP was associated with a 0.6-fold decreased risk for 30-day all
      cause mortality (OR 0.60, 95% CI 0.39 to 0.92). However, the difference in the
      risk for permanent pacemaker implantation, grade 2, or higher aortic
      regurgitation, stroke was noted to be significant only in the subgroup of the
      CoreValve-dominating studies. In conclusion, no-BP before transcatheter aortic
      valve implantation was not only safe and feasible but was also associated with
      fewer complications and short-term mortality in selected patients especially
      using self-expandable valve. 

PMID- 27026642
TI  - The Effect of Perioperative Corticosteroids in Total Hip Arthroplasty: A
      Prospective Double-Blind Placebo Controlled Pilot Study.
AB  - BACKGROUND: Surgery produces a rapid rise in interleukin 6 (IL-6) which may
      increase the risk of deep vein thrombosis and medical complications.
      Perioperative corticosteroids suppress IL-6 release in patients undergoing total
      knee arthroplasty. This study evaluates the effects of a perioperative
      corticosteroid regimen on IL-6 formation, thrombogenesis, fibrinolysis, and
      clinical outcomes in patients undergoing unilateral, uncemented, total hip
      arthroplasty. METHODS: Twenty-seven patients (14 placebo and 13 study) were
      enrolled in this randomized, double-blind, placebo-controlled trial. The study
      group received 20 mg of prednisone orally followed by 2 doses of intravenous
      hydrocortisone, each 8 hours apart. Blood was drawn at several time points for IL
      6, prothrombin fragment 1.2, and plasmin-alpha-2-antiplasmin complex, a marker of
      fibrinolysis. In-hospital visual analog pain (visual analog scale) scores,
      patient-controlled analgesia use, and ability to climb stairs were recorded.
      RESULTS: Mean serum IL-6 levels at 6 and 24 hours postoperatively were
      significantly lower for the study group, whereas serum prothrombin fragment 1.2
      and plasmin-alpha-2-antiplasmin were not statistically different at any study
      time point. Average pain scores were similar (P > .05), but study group
      experience less severe pain (P < .01) and less patient-controlled analgesia (P =
      .02). At 3 months, 4 patients in the placebo and 1 patient in the study group had
      difficulty going up and down staircases (P = .08). CONCLUSION: The use of
      corticosteroids was associated with a statistically significant decrease in IL-6
      at 6 and 24 hours postoperatively but did not affect thrombogenic markers. The
      study group had improved postoperative analgesia and a trend toward improved
      functional outcome at 3 months postoperatively.

PMID- 27026643
TI  - Does Prior Surgery for Femoroacetabular Impingement Compromise Hip Arthroplasty
      Outcomes?
AB  - BACKGROUND: Open and arthroscopic approaches have been described to address
      femoroacetabular impingement (FAI). Despite good outcomes, there is a subset of
      patients who subsequently require total hip arthroplasty (THA). However, there is
      a paucity of data on the outcomes of THA after surgery for FAI. The purpose of
      this study was to determine whether clinical outcomes of THA are affected by
      prior open or arthroscopic treatment of FAI. METHODS: This case-matched
      retrospective review included 23 patients (24 hips) that underwent THA after
      previous surgery for FAI (14 arthroscopic and 10 open) and compared them to 24
      matched controls with no history of prior surgery on the operative hip. The
      controls were matched for age, sex, surgical approach, implants used, and
      preoperative modified Harris hip score (mHHS) did not differ between groups. The
      primary outcome measure was the mHHS. Operative time, blood loss, and the
      presence of heterotopic ossification after THA were also compared between groups.
      RESULTS: There was no significant difference in mean mHHS between the FAI
      treatment group 92.9 +/- 12.7 and controls 95.2 +/- 6.6 (P = .43) at a mean
      follow-up after THA of 33 (24-70) months. Increased operative times were noted
      for THA after surgical hip dislocation (SHD; mean 109.3 +/- 29.8) compared to
      controls (mean 88.0 +/- 24.2; P < .05). There was no significant difference in
      blood loss between groups. The occurrence of heterotopic ossification was
      significantly higher after SHD compared to controls (P < .05). CONCLUSIONS:
      Clinical outcomes after THA are not affected by prior open or arthroscopic
      procedures for FAI. However, increased operative times and an increased risk of
      heterotopic ossification were noted after SHD.

PMID- 27026644
TI  - Tranexamic Acid Can Be Administered to Arthroplasty Patients Who Receive Aspirin
      for Venous Thromboembolic Prophylaxis.
AB  - BACKGROUND: Venous thromboembolism (VTE) is not uncommon after total joint
      arthroplasty (TJA). Various prophylactic agents have been used to minimize this
      complication after TJA. Numerous studies have demonstrated that acetylsalicylic
      acid (ASA) has equivalent efficacy to other agents in preventing VTE after TJA.
      However, some have expressed theoretical concern that ASA may not be an adequate
      VTE prophylaxis in TJA patients receiving tranexamic acid (TA), which is an
      antifibrinolytic agent. The purpose of the study was to assess the safety and
      efficacy of administering systemic TA in TJA patients who also received ASA for
      VTE prophylaxis. METHODS: A retrospective study was conducted on 2835 consecutive
      patients (1678 receiving TA and 1157 not receiving TA) who underwent primary or
      revision TJA between January 2013 and June 2014 and also received aspirin for VTE
      prophylaxis. The incidence of symptomatic deep vein thrombosis and pulmonary
      embolism was evaluated. RESULTS: Blood loss and transfusion rates were
      significantly lower in the TA group compared to the non-TA group (P < .0001, P =
      .017, respectively). The incidence of VTE, bleeding events, and wound
      complications was similar (P > .05) between the groups. CONCLUSION: In patients
      undergoing TJA who receive ASA for VTE prophylaxis, TA reduces bleeding and
      transfusions without increasing the incidence of subsequent VTE.

PMID- 27026645
TI  - Importance of Proper Utilization of International Classification of Diseases 10th
      Revision and Clinical Documentation in Modern Payment Models.
AB  - BACKGROUND: Health care payment models are changing rapidly, and the measurement
      of outcomes and costs is increasing. METHODS: With the implementation of
      International Classification of Diseases 10th revision (ICD-10) codes, providers
      now have the ability to introduce a precise array of diagnoses for their
      patients. RESULTS: More specific diagnostic codes do not eliminate the potential
      for vague application, as was seen with the utility of ICD-9. Complete, accurate,
      and consistent data that reflect the risk, severity, and complexity of care are
      becoming critically important in this new environment. Orthopedic specialty
      organizations must be actively involved in influencing the definition of value
      and risk in the patient population. CONCLUSION: Now is the time to use the ICD-10
      diagnostic codes to improve the management of patient conditions in data.

PMID- 27026646
TI  - Ethnic Barriers to Utilization of Total Joint Arthroplasty Among Chinese
      Immigrants in the United States.
AB  - BACKGROUND: Previous studies have documented disparities in total joint
      arthroplasty (TJA) utilization among African American and Hispanic patients, but
      utilization among non-English-speaking Chinese patients in the United States has
      not been studied. METHODS: To quantify the utilization rate and detect ethnic
      factors effecting TJA utilization in non-English-speaking Chinese patients, data
      were gathered prospectively from the practice of a single fellowship-trained
      Caucasian surgeon from October 2012 to February 2013. A customized survey was
      drafted and validated in collaboration with a social scientist. Questions
      assessed demography, lifestyle factors, socioeconomic status, language skills,
      cultural beliefs, and prior experience with surgery. Surveys were administered in
      patients' native language and were collected in a blinded fashion. RESULTS:
      Overall, 269 patients were surveyed (157 Caucasian and 65 Chinese), 85 of which
      were recommended surgery (42 Caucasian and 26 Chinese). Seventy-six percent of
      Caucasian patients elected surgery, compared to 35% of Chinese patients. A
      multivariate logistic regression showed Chinese ethnicity to be a significant
      predictor of surgical decision after controlling for age, gender, socioeconomic
      status, and education. Several questions drafted to detect cultural differences
      in the aforementioned 6 categories were answered significantly differently (P <
      .05, chi-square). CONCLUSION: Language, lack of familiarity with surgery, lack of
      TJA knowledge, family members' role in decision making, and preference for a
      doctor of the same race may contribute to decreased utilization of TJA in this
      population. We believe a better understanding of the cultural beliefs and
      behaviors of Chinese patients will help physicians provide more optimal care to
      this patient population.

PMID- 27026647
TI  - Journey Toward High Reliability: A Comprehensive Safety Program to Improve
      Quality of Care and Safety Culture in a Large, Multisite Radiation Oncology
      Department.
AB  - BACKGROUND: High-reliability organizations (HROs) focus on continuous
      identification and improvement of safety issues. We sought to advance a large,
      multisite radiation oncology department toward high reliability through the
      implementation of a comprehensive safety culture (SC) program at the University
      of Pennsylvania Department of Radiation Oncology. METHODS: In 2011, with guidance
      from safety literature and experts in HROs, we designed an SC framework to reduce
      radiation errors. All state-reported medical events (SRMEs) from 2009 to 2016
      were retrospectively reviewed and plotted on a control chart. Changes in SC grade
      were assessed using the Agency for Healthcare Research and Quality Hospital
      Survey. Outcomes measured included the number of radiation treatment fractions
      and days between SRMEs, as well as SC grade. RESULTS: Multifaceted safety
      initiatives were implemented at our main academic center and across all network
      sites. Postintervention results demonstrate increased staff fundamental safety
      knowledge, enhanced peer review with an electronic system, and special cause
      variation of SRMEs on control chart analysis. From 2009 to 2016, the number of
      days and fractions between SRMEs significantly increased, from a mean of 174 to
      541 days (P < .0075) and 21,678 to 113,104 fractions (P < .0028) preintervention
      and postintervention, respectively. Agency for Healthcare Research and Quality
      results demonstrate a high patient SC grade over time. CONCLUSION: Our journey
      toward becoming an HRO has led to the development of a robust SC through a
      comprehensive safety framework. Our multifaceted initiatives, focusing on culture
      and system changes, can be successfully implemented in a large academic radiation
      oncology department to yield measurable improvements in SC and outcomes.

PMID- 27026648
TI  - Low Enrollment of Adolescents and Young Adults Onto Cancer Trials: Insights From
      the Community Clinical Oncology Program.
AB  - PURPOSE: Stagnant outcomes for adolescents and young adults (AYAs; 15 to 39 years
      old) with cancer are partly attributed to poor enrollment onto clinical trials.
      The National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP)
      was developed to improve clinical trial participation in the community setting,
      where AYAs are most often treated. Further, many CCOP sites had pediatric and
      medical oncologists with collaborative potential for AYA recruitment and care.
      For these reasons, we hypothesized that CCOP sites enrolled proportionately more
      AYAs than non-CCOP sites onto Children's Oncology Group (COG) trials. METHODS:
      For the 10-year period 2004 through 2013, the NCI Division of Cancer Prevention
      database was queried to evaluate enrollments into relevant COG studies. The
      proportional enrollment of AYAs at CCOP and non-CCOP sites was compared and the
      change in AYA enrollment patterns assessed. All sites were COG member
      institutions. RESULTS: Although CCOP sites enrolled a higher proportion of
      patients in cancer control studies than non-CCOP sites (3.5% v 1.8%; P < .001),
      they enrolled a lower proportion of AYAs (24.1% v 28.2%, respectively; P < .001).
      Proportional AYA enrollment at CCOP sites decreased during the intervals 2004
      through 2008 and 2009 through 2013 (26.7% v 21.7%; P < .001). CONCLUSION: Despite
      oncology practice settings that might be expected to achieve otherwise, CCOP
      sites did not enroll a larger proportion of AYAs in clinical trials than
      traditional COG institutions. Our findings suggest that the CCOP (now the NCI
      Community Oncology Research Program) can be leveraged for developing targeted
      interventions for overcoming AYA enrollment barriers.

PMID- 27026649
TI  - Experience of the National Cancer Institute Community Cancer Centers Program on
      Community-Based Cancer Clinical Trials Activity.
AB  - PURPOSE: A goal of the National Cancer Institute Community Cancer Centers Program
      (NCCCP) was to improve cancer research capacity in community settings. We
      examined research capacity development during the pilot phase of the NCCCP within
      the context of national trends in clinical trial activity with respect to the
      number and phase of trials, total accrual, and accrual of underserved
      populations. MATERIALS AND METHODS: We examined self-reported data from NCCCP
      sites during 2007 to 2010, supplemented with data from the National Cancer
      Institute Cancer Therapy Evaluation Program. RESULTS: Trial availability and
      accrual improved more quickly at NCCCP sites compared with national trends. Phase
      III trial availability increased 8% nationally versus 16% across NCCCP sites, and
      accrual increased 30% nationally versus 133% across NCCCP sites. Accrual of
      racial and ethnic minorities rose 82%, from 83 to 151 patients, and accrual of
      patients age >= 65 years rose by 221%, from 200 to 641 patients. Change in trial
      portfolio and accrual differed by sophistication of the site and by prior
      experience in conducting clinical trials at the site. CONCLUSION: Despite the
      short duration, the NCCCP pilot resulted in an increase in the number of open
      trials as well as patient accrual at a faster rate than that observed nationally.
      These results, coupled with insights into the relative success of sites with
      varying sophistication at the outset, provide promise that lessons learned can be
      applied more broadly to increase research participation.

PMID- 27026650
TI  - Two Fatal Intoxications with Cyanohydrins.
AB  - Cyanohydrins, also be called cyanoalcohols, are important industrial precursors
      to carboxylic acids and some amino acids. Acetone cyanohydrin (ACH) and
      formaldehyde cyanohydrin (glycolonitrile, FCH), which are the typical examples of
      cyanohydrins, are classified as extremely hazardous substances. As the
      cyanohydrins can readily decompose, and it is hard to find cyanohydrins in
      gastric contents and heart blood, the determination study in biological samples
      can be divided into two parts: the first is the determination of HCN by using a
      Prussian blue reaction and the HS-GC-MSD after derivatization by chloramine-T.
      The second is the determination of acetone or formaldehyde. In this part,
      headspace gas chromatography with flame ionization detector (HS-GC-FID) and solid
      phase microextraction (SPME)-gas chromatography with mass spectrometric detectors
      (GC-MSD) had been used. In this report, we reported two fatal intoxication cases
      of ACH and FCH; one person was killed by his wife by poisoning his food and the
      other was suicide by poison. Two real cases of ACH and FCH in human blood and
      gastric contents have been analyzed by using the above-mentioned method. The
      Prussian blue reaction was positive in the two cases. The peaks of acetone with
      retention times of 0.998 min appear in specimens of the deceased are consistent
      with the retention times of pure acetone. The peaks of formaldehyde with a
      retention time of 1.658 min appear in heart blood of the deceased, and the
      retention time of formaldehyde of the liquid is 1.674 min, which are consistent
      with the retention times of pure formaldehyde (1.673 min). 

PMID- 27026651
TI  - Real-time bilinear rotation decoupling in absorptive mode J-spectroscopy:
      Detecting low-intensity metabolite peak close to high-intensity metabolite peak
      with convenience.
AB  - "Pure shift" NMR spectra display singlet peak per chemical site. Thus, high
      resolution is offered at the cost of valuable J-coupling information. In the
      present work, real-time BIRD (BIlinear Rotation Decoupling) is applied to the
      absorptive-mode 2D J-spectroscopy to provide pure shift spectrum in the direct
      dimension and J-coupling information in the indirect dimension. Quite often in
      metabolomics, proton NMR spectra from complex bio-fluids display tremendous
      signal overlap. Although conventional J-spectroscopy in principle overcomes this
      problem by separating the multiplet information from chemical shift information,
      however, only magnitude mode of the experiment is practical, sacrificing much of
      the potential high resolution that could be achieved. Few J-spectroscopy methods
      have been reported so far that produce high-resolution pure shift spectrum along
      with J-coupling information for crowded spectral regions. In the present work,
      high-quality J-resolved spectrum from important metabolomic mixture such as
      tissue extract from rat cortex is demonstrated. Many low-intensity metabolite
      peaks which are obscured by the broad dispersive tails from high-intensity
      metabolite peaks in regular magnitude mode J-spectrum can be clearly identified
      in real-time BIRD J-resolved spectrum. The general practice of removing such
      spectral overlap is tedious and time-consuming as it involves repeated sample
      preparation to change the pH of the tissue extract sample and subsequent spectra
      recording.

PMID- 27026652
TI  - Electrophysiological evidence during episodic prospection implicates medial
      prefrontal and bilateral middle temporal gyrus.
AB  - fMRI studies have implicated the medial prefrontal cortex and medial temporal
      lobe, components of the default mode network (DMN), in episodic prospection. This
      study compared quantitative EEG localized to these DMN regions during prospection
      and during resting and while waiting for rewards. EEG was recorded in twenty-two
      adults while they were asked to (i) envision future monetary episodes; (ii) wait
      for rewards and (iii) rest. Activation sources were localized to core DMN
      regions. EEG power and phase coherence were compared across conditions.
      Prospection, compared to resting and waiting, was associated with reduced power
      in the medial prefrontal gyrus and increased power in the bilateral medial
      temporal gyrus across frequency bands as well as greater phase synchrony between
      these regions in the delta band. The current quantitative EEG analysis confirms
      prior fMRI research suggesting that medial prefrontal and medial temporal gyrus
      interactions are central to the capacity for episodic prospection.

PMID- 27026654
TI  - Expression of receptor protein tyrosine phosphatase delta, PTPdelta, in mouse
      central nervous system.
AB  - Protein tyrosine phosphate delta (PTPdelta), one of the receptor type IIa protein
      tyrosine phosphates, is known for its roles in axon guidance, synapse formation,
      cell adhesion, and tumor suppression. Alternative splicing of this gene generates
      at least four (A-D) isoforms; however, the major isoform in vivo is yet to be
      determined. The protein localization has neither been revealed. We have generated
      anti-mouse PTPdelta-specific monoclonal antibody and analyzed the protein
      expression in wild-type and Ptpdelta knockout mice. Immunoblot analysis of
      various organs revealed that neuronal tissues express both C-and D-isoforms of
      PTPdelta, whereas non-neuronal tissues express only C-isoform.
      Immunohistochemistry of wild-type or Ptpdelta heterozygous sections showed that
      olfactory bulb, cerebral cortex, hippocampus, cerebellum, and several nuclei in
      brain stem exhibit moderate to strong positive signals. These signals were absent
      in Ptpdelta knockout specimens. Higher magnification revealed differences between
      expression patterns of PTPdelta mRNA and its protein product. In hippocampus,
      weak mRNA expression in CA1 stratum pyramidale but strong immunostaining in the
      stratum lacunosum moleculare was observed, suggesting the axonal expression of
      PTPdelta in the entorhinal cortical afferents. Olfactory mitral cells exhibited
      mRNA expression in cell bodies and protein localization in their dendritic
      fields, glomerular and external plexiform layers. Nissl staining showed that the
      external plexiform layer was reduced in Ptpdelta knockout mice. Golgi
      impregnation confirmed the poor dendritic growth of homozygous mitral cells.
      These results suggest that PTPdelta may localize in axons as well as in dendrites
      to regulate their elaboration in the central nervous system.

PMID- 27026653
TI  - Lysosome and endoplasmic reticulum quality control pathways in Niemann-Pick type
      C disease.
AB  - Lysosomal storage diseases result from inherited deficiencies of lysosomal
      hydrolytic activities or lipid transport. Collectively, these disorders are a
      common cause of morbidity in the pediatric population and are often associated
      with severe neurodegeneration. Among this group of diseases is Niemann-Pick type
      C, an autosomal recessive disorder of lipid trafficking that causes cognitive
      impairment, ataxia and death, most often in childhood. Here, we review the
      current knowledge of disease pathogenesis, with particular focus on insights
      gleaned from genetics and the study of model systems. Critical advances in
      understanding mechanisms that regulate intracellular cholesterol trafficking have
      emerged from this work and are highlighted. We review effects of disease-causing
      mutations on quality control pathways involving the lysosome and endoplasmic
      reticulum, and discuss how they function to clear the most common mutant protein
      found in Niemann-Pick type C patients, NPC1-I1061T. Finally, we summarize
      insights into the mechanisms that degrade misfolded transmembrane proteins in the
      endoplasmic reticulum and how manipulating these quality control pathways may
      lead to the identification of novel targets for disease-modifying therapies. This
      article is part of a Special Issue entitled SI:Autophagy.

PMID- 27026655
TI  - Visual masking with frontally applied pre-stimulus TMS and its subject-specific
      neural correlates.
AB  - The visibility of a visual target stimulus depends on the local state of the
      early visual cortex shortly before the stimulus itself is presented. This view is
      supported by the observation that occipitally applied pre-stimulus TMS can
      disrupt subsequent information processing leading to visual masking effects.
      According to another line of accumulating evidence, however, global pre-stimulus
      connectivity patterns could be as crucial as local cortical states. In line with
      the latter view we show that pre-stimulus masking occurs even if TMS is directed
      to the frontal cortex. Importantly, the individual extent of this effect is
      strongly correlated with the subject-specific peak latency of a late positive TMS
      evoked potential. Our results thus suggest a third type of masking occurring
      neither through direct interaction with visual areas nor by a modal visual
      masking input. Our results also shed light on the inter-individual differences in
      TMS research in general.

PMID- 27026656
TI  - Reduced cerebrovascular reserve is regionally associated with cortical thickness
      reductions in children with sickle cell disease.
AB  - Sickle cell disease (SCD) is a genetic disorder which adversely affects
      cerebrovascular health. Previous studies have demonstrated regional cortical
      thinning in SCD. However, the reason behind regional reductions in cortical
      thickness remains unclear. Therefore, we aimed to explore the possible link
      between the state of cerebrovascular health and cortical thickness. In this
      study, we obtained magnetic resonance (MR) based measures of cerebrovascular
      reactivity (CVR), a measure of vascular health, and cortical thickness in SCD
      patients (N=60) and controls of similar age and similar gender ratio (N=27). The
      group comparison analysis revealed significant regionally specific reductions in
      CVR and cortical thickness in the SCD group compared to the controls. In
      addition, a regional association analysis was performed between CVR and cortical
      thickness in the SCD group which revealed a significant regional association in
      several brain regions with the highest strength of association observed in the
      left cuneus, right post central gyrus and the right temporal pole. The regional
      association analysis revealed that significant associations were found in brain
      regions with high metabolic activity (anterior cingulate, posterior cingulate,
      occipital gyrus, precuneus) thus demonstrating that these regions could be most
      vulnerable to structural damage under hypoxic conditions.

PMID- 27026657
TI  - Working memory filtering continues to develop into late adolescence.
AB  - While most measures of working memory (WM) performance have been shown to plateau
      by mid-adolescence and developmental changes in fronto-parietal regions
      supporting WM encoding and maintenance have been well characterized, little is
      known about developmental variation in WM filtering. We investigated the
      possibility that the neural underpinnings of filtering in WM reach maturity later
      in life than WM function without filtering. Using a cued WM filtering task (McNab
      and Klingberg, 2008), we investigated neural activity during WM filtering in a
      sample of 64 adults and adolescents. Regardless of age, increases in WM activity
      with load were concentrated in the expected fronto-parietal network. For adults,
      but not adolescents, recruitment of the basal ganglia during presentation of a
      filtering cue was associated with neural and behavioral indices of successful
      filtering, suggesting that WM filtering and related basal ganglia function may
      still be maturing throughout adolescence and into adulthood. 

PMID- 27026659
TI  - Automated Image Analysis for Determination of Antibody Titers Against
      Occupational Bacterial Antigens Using Indirect Immunofluorescence.
AB  - Employees who are exposed to high concentrations of microorganisms in bioaerosols
      frequently suffer from respiratory disorders. However, etiology and in particular
      potential roles of microorganisms in pathogenesis still need to be elucidated.
      Thus, determination of employees' antibody titers against specific occupational
      microbial antigens may lead to identification of potentially harmful species.
      Since indirect immunofluorescence (IIF) is easy to implement, we used this
      technique to analyze immunoreactions in human sera. In order to address
      disadvantageous inter-observer variations as well as the absence of quantifiable
      fluorescence data in conventional titer determination by eye, we specifically
      developed a software tool for automated image analysis. The 'Fluorolyzer'
      software is able to reliably quantify fluorescence intensities of antibody-bound
      bacterial cells on digital images. Subsequently, fluorescence values of single
      cells have been used to calculate non-discrete IgG titers. We tested this
      approach on multiple bacterial workplace isolates and determined titers in sera
      from 20 volunteers. Furthermore, we compared image-based results with the
      conventional manual readout and found significant correlation as well as
      statistically confirmed reproducibility. In conclusion, we successfully employed
      'Fluorolyzer' for determination of titers against various bacterial species and
      demonstrated its applicability as a useful tool for reliable and efficient
      analysis of immune response toward occupational exposure to bioaerosols. 

PMID- 27026658
TI  - Effectiveness of influenza vaccination for preventing influenza-related
      complications in people with asthma: a systematic review protocol.
AB  - INTRODUCTION: Influenza vaccination is administered annually as a preventive
      measure against influenza infection and influenza-related complications in high
      risk individuals, such as those with asthma. However, the effectiveness of
      influenza vaccination in people with asthma against influenza-related
      complications is still not well established. METHODS AND ANALYSIS: We will search
      the following databases: MEDLINE (Ovid), EMBASE (Ovid), Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of
      Controlled Trials (CENTRAL), Scopus, Cochrane Database of Systematic Reviews
      (CDSR), Web of Science Core Collection, Science direct, WHO Library Information
      System (WHOLIS), Global Health Library and Chinese databases (CNKI, Wanfang and
      ChongQing VIP) from Jan 1970 to Jan 2016 for observational and experimental
      studies on effectiveness of influenza vaccine in people with asthma. The
      identification of studies will be complemented with the searching of the
      reference lists and citations, and contacting influenza vaccine manufacturers to
      identify unpublished or ongoing studies. Two reviewers will extract data and
      appraise the quality of each study independently. Separate meta-analyses will be
      undertaken for observational and experimental evidence using fixed-effect or
      random-effects models, as appropriate. ETHICS AND DISSEMINATION: Formal ethical
      approval is not required, as primary data will not be collected. The review will
      be disseminated in peer-reviewed publications and conference presentations.

PMID- 27026660
TI  - Psychosocial Work Conditions and Burnout Among Brazilian Bank Employees: A Cross
      Sectional Study.
AB  - OBJECTIVES: Changes in the modern economy have affected the financial sector.
      Time pressures, excessive work demands, and job stress are frequent concerns
      among bank employees, which might predispose them to burnout symptoms. The
      objective of the present study was to investigate the association between burnout
      symptoms and exposure to psychosocial work conditions in bank employees. METHODS:
      A cross-sectional study of 1046 bank employees was carried out in Para and Amapa,
      northern Brazil. We applied a self-administered questionnaire evaluating socio
      demographic characteristics, burnout (Maslach Burnout Inventory), and two job
      stress models (Demand-Control-Support and Effort-Reward Imbalance). Two levels of
      burnout symptoms were analysed: moderate level of burnout (MLB) and high level of
      burnout (HLB). Logistic regression models were used to estimate associations
      between the two levels of burnout and the two stress models, controlling for
      relevant covariates. RESULTS: The overall prevalence of burnout was 71.8% (31.1%
      for HLB; 40.7% for MLB), regardless of gender. Exposure to adverse psychosocial
      conditions in the workplace, such as high strain, low social support at work,
      high effort/low reward, and over commitment showed strong association with HLB
      and MLB, and these associations were independent of age, gender, and other
      occupational characteristics. CONCLUSIONS: We found that psychosocial conditions
      in the financial sector involving high strain, low social support at work, high
      effort/low reward, and over commitment represent possible risk factors for
      moderate and HLB symptoms in bank employees.

PMID- 27026661
TI  - Editorial: Remembering Bryan Lask.

PMID- 27026662
TI  - The transition into adoptive parenthood: Adoption as a process of continued
      unsafe uncertainty when family scripts collide.
AB  - Our prospective study investigated couples' expectations of adoptive parenthood
      and explored how these changed with their actual experience of parenthood. Six
      heterosexual couples were interviewed just before placement began and 6 months
      after the children had arrived. Interpretative Phenomenological Analysis (IPA)
      was used to analyse both sets of interview data. Expectations of adoptive
      parenthood mostly transformed smoothly into adoption experience for couples, but
      challenges were experienced when family scripts collided and a continued feeling
      of unsafe uncertainty then prevailed within these newly formed family systems.
      Family script collision seemed a particular problem for couples adopting sibling
      pairs. To further professional practice in working with families over the
      transition to adoptive parenting, we suggest that professionals keep in mind a
      framework that includes the following: Internal and external world influences on
      family members, Intergenerational issues, Family scripts and the Structural
      challenges of adoption (IIFS).

PMID- 27026664
TI  - COPE: A Pilot Study With Urban-Dwelling Minority Sixth-Grade Youth to Improve
      Physical Activity and Mental Health Outcomes.
AB  - Approximately one in three preadolescents (34%) is obese/overweight and one in
      four (25%) experience a mental health issue. Urban youth suffer from higher rates
      of these problems, and at earlier ages than their peers. This study's purpose was
      to determine feasibility/acceptability and preliminary effects of the COPE
      (Creating Opportunities for Personal Empowerment) Healthy Lifestyles TEEN
      (Thinking, Emotion, Exercise, and Nutrition) intervention on physical activity
      (PA) and mental health outcomes of 11- to 13-year-olds. A one group pre- and
      posttest design was used in a Midwest urban middle school. Preadolescents (n =
      31) who received COPE reported significant decreases in anxiety and increases in
      healthy lifestyle beliefs and PA. Further, preadolescents at baseline with
      elevated anxiety, depression, suicide risk, and below average self-concept who
      received COPE reported significant increases in self-concept and decreases in
      anxiety, depression, and suicidal ideation. The COPE program is a promising
      intervention that can improve physical and mental health outcomes. 

PMID- 27026663
TI  - Development of Health-Related Quality of Life Instruments for Young Children With
      Disorders of Sex Development (DSD) and Their Parents.
AB  - Objective: Research in disorders of sex development (DSD) is hindered by a lack
      of standardized measures sensitive to the experiences of affected children and
      families. We developed and evaluated parent proxy (children 2-6 years) and parent
      self-report (children <=6 years) health-related quality of life (HRQoL)
      instruments for DSD. Methods: Items were derived from focus groups and open-ended
      interviews. Clarity and comprehensiveness were assessed with cognitive
      interviews. Psychometric properties were examined in a field survey of 94
      families. Results: Measures demonstrated adequate to good psychometrics,
      including internal consistency, test-retest reliability, convergent validity, and
      ability to detect known-group differences. Parents reported greatest stress on
      Early Experiences , Surgery , and Future Concerns scales. Conclusions: These
      instruments identify patients' and families' needs, monitor health and quality of
      life status, and can evaluate clinical interventions. Findings highlight the need
      for improved psychosocial support during the diagnostic period, better parent
      provider communication, and shared decision-making. HRQoL measures are needed for
      older youth.

PMID- 27026665
TI  - Presenteeism Attitudes and Behavior Among Missouri Kindergarten to Twelfth Grade
      (K-12) School Nurses.
AB  - Working while ill (presenteeism) with symptoms of influenza-like illness can
      contribute to outbreaks, but little is known about school nurse presenteeism.
      Missouri Association of School Nurses members (N = 396) were sent a survey in
      2013/2014. A chi square test was conducted to compare having a school culture
      that encourages presenteeism versus actual sick leave policies. Multivariate
      logistic regression was conducted to delineate factors associated with
      presenteeism. In total, 133 school nurses participated (33.6% response rate).
      Almost half (42.1%, n = 56) reported presenteeism. Nurses were more likely to
      feel pressure to engage in presenteeism than reported punitive sick leave
      policies (14.3% vs. 3.8%, chi2 = 18.3, p < .001). Presenteeism was associated
      with perceived pressure, odds ratio (OR) = 4.8, confidence interval (CI) = [1.5,
      15.8], p < .01, and having a mild illness, OR = 3.6, CI = [1.4, 9.7], p = .01.
      Many school nurses engage in presenteeism, and this appears to be associated with
      organizational cultural norms rather than established sick leave policies.

PMID- 27026667
TI  - Madness in historical perspective.

PMID- 27026666
TI  - Prediction of denosumab effects on bone remodeling: A combined pharmacokinetics
      and finite element modeling.
AB  - Denosumab is a fully human monoclonal antibody that inhibits receptor activator
      of nuclearfactor-kappa B ligand (RANKL). This key mediator of osteoclast
      activities has been shown to inhibit osteoclast differentiation and hence, to
      increase bone mineral density (BMD) in treated patients. In the current study, we
      develop a computer model to simulate the effects of denosumab treatments (dose
      and duration) on the proximal femur bone remodeling process quantified by the
      variation in proximal femur BMD. The simulation model is based on a coupled
      pharmacokinetics model of denosumab with a pharmacodynamics model consisting of a
      mechanobiological finite element remodeling model which describes the activities
      of osteoclasts and osteoblasts. The mechanical behavior of bone is described by
      taking into account the bone material fatigue damage accumulation and
      mineralization. A coupled strain-damage stimulus function is proposed which
      controls the level of bone cell autocrine and paracrine factors. The cellular
      behavior is based on Komarova et al.'s (2003) dynamic law which describes the
      autocrine and paracrine interactions between osteoblasts and osteoclasts and
      computes cell population dynamics and changes in bone mass at a discrete site of
      bone remodeling. Therefore, when an external mechanical stress is applied, bone
      formation and resorption is governed by cell dynamics rather than by adaptive
      elasticity approaches. The proposed finite element model was implemented in the
      finite element code Abaqus (UMAT routine). In order to perform a preliminary
      validation, in vivo human proximal femurs were selected and scanned at two
      different time intervals (at baseline and at a 36-month interval). Then, a 3D FE
      model was generated and the denosumab-remodeling algorithm was applied to the
      scans at t0 simulating daily walking activities for a duration of 36 months. The
      predicted results (density variation) were compared to existing published ones
      performed on a human cohort (FREEDOM).

PMID- 27026668
TI  - A first for health care education.

PMID- 27026669
TI  - CD4 measurement in a 54-year-old man with sustained HIV-1 viral suppression.

PMID- 27026670
TI  - Many eligible federal inmates won't get new hepatitis treatment.

PMID- 27026671
TI  - Pustules of the fingers: acrodermatitis continua.

PMID- 27026673
TI  - Budget tackles social determinants of health.

PMID- 27026672
TI  - Recommendations on screening for developmental delay.

PMID- 27026674
TI  - Noninvasive neurostimulation methods for migraine therapy: The available
      evidence.
AB  - Background Migraine is one of the most disabling neurological disorders. The
      current pharmacological armamentarium is not satisfying for a large proportion of
      patients because the responder rate does not exceed 50% on average and the most
      effective drugs often induce intolerable side effects. During recent years,
      noninvasive central and peripheral neuromodulation methods have been explored for
      migraine treatment. Overview A review of the available evidence suggests that
      noninvasive neuromodulation techniques could be beneficial for migraine patients.
      The transcranial stimulation methods allow modulating selectively cortical
      activity and can thus be curtailed to the patient's pathophysiological profile,
      while transcutaneous stimulation of pericranial nerves likely modulates central
      pain control centers. Occipital single-pulse transcranial magnetic stimulation
      and transcutaneous supraorbital stimulation have the strongest evidence
      respectively for acute and preventive treatment. Transcranial direct current
      stimulation and repetitive magnetic stimulation are promising in pilot studies,
      but large sham-controlled trials are not yet available. Conclusions The
      noninvasive neurostimulation methods are promising for migraine treatment and
      devoid of serious adverse effects allowing their combination with drug therapies.
      Their application in clinical practice will depend on the industry's capacity to
      develop portable and user-friendly devices, and on the scientists' capacity to
      prove their efficacy in randomized sham-controlled trials.

PMID- 27026675
TI  - Risk of Congestive Heart Failure in Early Breast Cancer Patients Undergoing
      Adjuvant Treatment With Trastuzumab: A Meta-Analysis.
AB  - BACKGROUND: The use of trastuzumab has proven to be a successful strategy in
      patients with human epidermal growth factor receptor 2 (HER2)-positive breast
      cancer; however, it is associated with an increased risk of cardiac dysfunction.
      We performed an up-to-date, comprehensive meta-analysis to clarify the risk of
      congestive heart failure (CHF) in patients with early breast cancer receiving
      different durations of adjuvant trastuzumab with the longest-term follow-up.
      METHODS: Eligible studies included randomized control trials of HER2-positive
      early breast cancer patients with or without trastuzumab in adjuvant
      chemotherapy. Adequate reporting of CHF data were required for inclusion.
      Statistical analyses were conducted to calculate the overall incidence, relative
      risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model.
      RESULTS: Six randomized control trials including 18,111 patients were identified.
      The overall incidence of high-grade CHF in patients treated with trastuzumab
      versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03
      5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed
      to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater
      than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus
      RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed
      for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2
      years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05
      5.49) compared with control groups. No evidence of publication bias was observed.
      CONCLUSION: Adjuvant trastuzumab therapy was strongly associated with an
      increased risk of significant CHF in patients with early breast cancer,
      particularly in 2-year use. IMPLICATIONS FOR PRACTICE: This comprehensive meta
      analysis evaluated the risk of congestive heart failure with a usage profile of
      adjuvant trastuzumab in patients with early breast cancer. Before initiating
      treatment with trastuzumab, a risk-benefit analysis for individual patients
      should be critically evaluated, considering that the prognosis is closely related
      to drug dose and duration of use. Cardiac function should be monitored throughout
      the treatment period and also during follow-up. Thus, early identification of
      trastuzumab-related cardiac dysfunction can allow effective medical intervention,
      elimination of symptoms, recovery of function, and continuation of trastuzumab
      therapy.

PMID- 27026676
TI  - FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic
      Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1.
AB  - : On October 2, 2015, the U.S. Food and Drug Administration (FDA) granted
      accelerated approval for pembrolizumab, a breakthrough therapy-designated drug,
      for the treatment of patients with metastatic non-small cell lung cancer (NSCLC)
      whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA
      approved test, and who have disease progression on or after platinum-containing
      chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal
      growth factor receptor, if appropriate. This indication was approved concurrently
      with the PD-L1 immunohistochemistry 22C3 pharmDx, a companion diagnostic test for
      patient selection based on PD-L1 tumor expression. The accelerated approval was
      granted based on durable objective response rate (ORR) and an acceptable toxicity
      profile demonstrated in a multicenter, open-label trial enrolling 550 patients
      with metastatic NSCLC. The efficacy population comprised 61 patients with tumors
      identified as strongly positive for PD-L1, and the confirmed ORR as determined by
      blinded independent central review was 41% (95% confidence interval: 28.6%,
      54.3%); all were partial responses. At the time of the analysis, responses were
      ongoing in 21 of 25 patients (84%), with 11 patients (44%) having response
      duration of >=6 months. The most commonly occurring (>=20%) adverse reactions
      included fatigue, decreased appetite, dyspnea, and cough. The most frequent
      (>=2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea,
      pulmonary embolism, and pneumonitis. Immune-mediated adverse reactions occurred
      in 13% of patients and included pneumonitis, colitis, hypophysitis, and thyroid
      disorders. The accelerated approval regulations describe approval of drugs and
      biologic products for serious and life-threatening illnesses based on a surrogate
      endpoint likely to predict clinical benefit. Under these regulations, a
      confirmatory trial or trials is required to verify and describe the benefit of
      pembrolizumab for patients with metastatic NSCLC. IMPLICATIONS FOR PRACTICE: This
      report presents key information on the U.S. Food and Drug Administration (FDA)
      accelerated approval of pembrolizumab for the treatment of patients with
      metastatic non-small cell lung cancer whose tumors express programmed death
      ligand 1, as determined by an FDA-approved test, and who have disease progression
      on or after platinum-containing chemotherapy or targeted therapy against
      anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate.
      The report discusses the data supporting the approval decision, specifically
      highlighting the incorporation of a companion diagnostic in the key study and the
      optimal dose of pembrolizumab.

PMID- 27026678
TI  - Into the Clinic With Nivolumab and Pembrolizumab.

PMID- 27026677
TI  - Clinical Trials of Antiangiogenesis Therapy in Recurrent/Persistent and
      Metastatic Cervical Cancer.
AB  - BACKGROUND: Treatment options for women with metastatic, persistent, or recurrent
      cervical cancer are limited and thus the disease portends a poor prognosis. It is
      critical to understand the pathophysiology of cervical cancer to better delineate
      therapeutic targets. The development of antiangiogenic therapies and their
      subsequent analysis in rigorous therapeutic trials have redefined current
      management strategies and is an exciting area of current exploration. RESULTS:
      Translational trials have furthered the understanding of molecular determinants
      of angiogenesis. Phase II trials have shown promising trends with developing
      antiangiogenic therapies. A practice-changing phase III trial has recently been
      published. Given the potential benefits and different toxicity spectrum compared
      with standard cytotoxic chemotherapy, antiangiogenic options are under active
      investigation for this vulnerable patient population. Emerging data are promising
      for other antiangiogenic-directed therapeutics, as well as cervical cancer
      molecular biomarkers to guide diagnosis and treatment. CONCLUSION: Antiangiogenic
      therapies have evolved during the past 20 years and remain an exciting area of
      current exploration. IMPLICATIONS FOR PRACTICE: Understanding of the angiogenic
      microenvironment has furthered understanding of tumor biology and management.
      Antiangiogenic therapies show promise for women with advanced cervical cancer. A
      review of the evolution of these biologic agents shows them to be an effective
      and tolerable management strategy for many patients in this vulnerable
      population, with exciting future potential.

PMID- 27026679
TI  - Prediction of Drug-Drug Interactions Arising from CYP3A induction Using a
      Physiologically Based Dynamic Model.
AB  - Using physiologically based pharmacokinetic modeling, we predicted the magnitude
      of drug-drug interactions (DDIs) for studies with rifampicin and seven CYP3A4
      probe substrates administered i.v. (10 studies) or orally (19 studies). The
      results showed a tendency to underpredict the DDI magnitude when the victim drug
      was administered orally. Possible sources of inaccuracy were investigated
      systematically to determine the most appropriate model refinement. When the
      maximal fold induction (Indmax) for rifampicin was increased (from 8 to 16) in
      both the liver and the gut, or when the Indmax was increased in the gut but not
      in liver, there was a decrease in bias and increased precision compared with the
      base model (Indmax = 8) [geometric mean fold error (GMFE) 2.12 vs. 1.48 and 1.77,
      respectively]. Induction parameters (mRNA and activity), determined for
      rifampicin, carbamazepine, phenytoin, and phenobarbital in hepatocytes from four
      donors, were then used to evaluate use of the refined rifampicin model for
      calibration. Calibration of mRNA and activity data for other inducers using the
      refined rifampicin model led to more accurate DDI predictions compared with the
      initial model (activity GMFE 1.49 vs. 1.68; mRNA GMFE 1.35 vs. 1.46), suggesting
      that robust in vivo reference values can be used to overcome interdonor and
      laboratory-to-laboratory variability. Use of uncalibrated data also performed
      well (GMFE 1.39 and 1.44 for activity and mRNA). As a result of experimental
      variability (i.e., in donors and protocols), it is prudent to fully characterize
      in vitro induction with prototypical inducers to give an understanding of how
      that particular system extrapolates to the in vivo situation when using an
      uncalibrated approach.

PMID- 27026680
TI  - Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype.
AB  - Sessile serrated colon adenoma/polyps (SSA/P) are found during routine screening
      colonoscopy and may account for 20% to 30% of colon cancers. However,
      differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer
      is challenging and complementary molecular markers are needed. In addition, the
      molecular mechanisms of colon cancer development from SSA/Ps are poorly
      understood. RNA sequencing (RNA-Seq) was performed on 21 SSA/Ps, 10 HPs, 10
      adenomas, 21 uninvolved colon, and 20 control colon specimens. Differential
      expression and leave-one-out cross-validation methods were used to define a
      unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon
      cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of
      colon cancers that may develop from SSA/Ps. A total of 1,422 differentially
      expressed genes were found in SSA/Ps relative to controls. Serrated polyposis
      syndrome (n = 12) and sporadic SSA/Ps (n = 9) exhibited almost complete (96%)
      gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of
      TCGA colon cancers with high microsatellite instability. A smaller 7-gene panel
      showed high sensitivity and specificity in identifying BRAF-mutant, CpG island
      methylator phenotype high, and MLH1-silenced colon cancers. We describe a unique
      gene signature in SSA/Ps that identifies a subset of colon cancers likely to
      develop through the serrated pathway. These gene panels may be utilized for
      improved differentiation of SSA/Ps from HPs and provide insights into novel
      molecular pathways altered in colon cancer arising from the serrated pathway.
      Cancer Prev Res; 9(6); 456-65. (c)2016 AACR.

PMID- 27026681
TI  - Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for
      Men with Type II Diabetes.
AB  - Racial/ethnic disparity in prostate cancer is under studied in men with diabetes
      who are at a higher risk of aggressive prostate cancer. This study assessed the
      race/ethnic disparity in prostate cancer incidence for men with type II diabetes
      (T2D) and whether the impact of metformin on prostate cancer incidence varied by
      race/ethnicity. We conducted a retrospective study in 76,733 male veterans with
      T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates
      and propensity scores of metformin use and race/ethnic group membership was
      utilized to compute the HR of prostate cancer incidence associated with
      race/ethnicity and compare HR associated with metformin use between race/ethnic
      groups. Mean follow-up was 6.4 +/- 2.8 years; 7% were Hispanics; 17% were African
      Americans (AA); mean age was 67.8 +/- 9.8 years; 5.2% developed prostate cancer;
      and 38.9% used metformin. Among these diabetic men without metformin use,
      prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic
      White (NHW). Use of metformin alone or metformin + statins was associated with a
      greater prostate cancer incidence reduction in Hispanics compared with NHW, but
      not between AA and NHW. Use of metformin + finasteride was associated with a
      greater prostate cancer incidence reduction in Hispanics and AA compared with
      NHW. Our results suggested that metformin treatment could be a potential strategy
      to reduce prostate cancer incidence in the minority populations who are at high
      risk for fatal prostate cancer. It will be important to further examine the
      pleiotropic effects of metformin in multi-race/ethnic prospective studies to
      better inform clinical management and potentially reduce racial/ethnic disparity
      in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87.
      (c)2016 AACR.

PMID- 27026683
TI  - In Vivo and In Vitro Characterization of Basal Insulin Peglispro: A Novel Insulin
      Analog.
AB  - The aim of this research was to characterize the in vivo and in vitro properties
      of basal insulin peglispro (BIL), a new basal insulin, wherein insulin lispro was
      derivatized through the covalent and site-specific attachment of a 20-kDa
      polyethylene-glycol (PEG; specifically, methoxy-terminated) moiety to lysine B28.
      Addition of the PEG moiety increased the hydrodynamic size of the insulin lispro
      molecule. Studies show there is a prolonged duration of action and a reduction in
      clearance. Given the different physical properties of BIL, it was also important
      to assess the metabolic and mitogenic activity of the molecule. Streptozotocin
      (STZ)-treated diabetic rats were used to study the pharmacokinetic and
      pharmacodynamic characteristics of BIL. Binding affinity and functional
      characterization of BIL were compared with those of several therapeutic insulins,
      insulin AspB10, and insulin-like growth factor 1 (IGF-1). BIL exhibited a
      markedly longer time to maximum concentration after subcutaneous injection, a
      greater area under the concentration-time curve, and a longer duration of action
      in the STZ-treated diabetic rat than insulin lispro. BIL exhibited reduced
      binding affinity and functional potency as compared with insulin lispro and
      demonstrated greater selectivity for the human insulin receptor (hIR) as compared
      with the human insulin-like growth factor 1 receptor. Furthermore, BIL showed a
      more rapid rate of dephosphorylation following maximal hIR stimulation, and
      reduced mitogenic potential in an IGF-1 receptor-dominant cellular model.
      PEGylation of insulin lispro with a 20-kDa PEG moiety at lysine B28 alters the
      absorption, clearance, distribution, and activity profile receptor, but does not
      alter its selectivity and full agonist receptor properties.

PMID- 27026682
TI  - C-Type Natriuretic Peptide Improves Left Ventricular Functional Performance at
      Rest and Restores Normal Exercise Responses after Heart Failure.
AB  - In heart failure (HF), the impaired left ventricular (LV) arterial coupling and
      diastolic dysfunction present at rest are exacerbated during exercise. C-type
      natriuretic peptide (CNP) is elevated in HF; however, its functional effects are
      unclear. We tested the hypotheses that CNP with vasodilating, natriuretic, and
      positive inotropic and lusitropic actions may prevent this abnormal exercise
      response after HF. We determined the effects of CNP (2 MUg/kg plus 0.4 MUg/kg per
      minute, i.v., 20 minutes) on plasma levels of cGMP before and after HF and
      assessed LV dynamics during exercise in 10 chronically instrumented dogs with
      pacing-induced HF. Compared with the levels before HF, CNP infusion caused
      significantly greater increases in cGMP levels after HF. After HF, at rest, CNP
      administration significantly reduced LV end-systolic pressure (PES), arterial
      elastance (EA), and end-diastolic pressure. The peak mitral flow (dV/dtmax) was
      also increased owing to decreased minimum LVP (LVPmin) and the time constant of
      LV relaxation (tau) (P < 0.05). In addition, LV contractility (EES) was
      increased. The LV-arterial coupling (EES/EA) was improved. The beneficial effects
      persisted during exercise. Compared with exercise in HF preparation, treatment
      with CNP caused significantly less important increases in PES but significantly
      decreased tau (34.2 vs. 42.6 ms) and minimum left ventricular pressure with
      further augmented dV/dtmax Both EES, EES/EA (0.87 vs. 0.32) were increased. LV
      mechanical efficiency improved from 0.38 to 0.57 (P < 0.05). After HF, exogenous
      CNP produces arterial vasodilatation and augments LV contraction, relaxation,
      diastolic filling, and LV arterial coupling, thus improving LV performance at
      rest and restoring normal exercise responses after HF.

PMID- 27026684
TI  - On the tumor risk from dental diagnostic X-ray exposure.

PMID- 27026685
TI  - Collaboration Across the Safety Net in the Era of Health Reform: Opportunities or
      Obstacles?
AB  - While implementation of the Patient Protection and Affordable Care Act brings
      significant opportunities for safety net providers (SNP), local systems vary in
      how well they adapt to the rapidly evolving environment. Collaboration may
      enhance SNP capacity to leverage opportunities in the health reform era. Our
      study examines key opportunities and challenges SNPs face under health reform and
      how providers use collaboration as a strategy to adapt to the new environment. A
      qualitative study of 78 executives at safety net organizations identified six
      priorities that pose both opportunities and challenges for SNP, and around which
      collaboration is used as a strategy to achieve common goals: Medicaid expansion,
      outreach and enrollment, capacity and access, health system transformation,
      health insurance exchanges, and reductions in government funding. Three types of
      collaborations emerged: policy and advocacy, community action, and practice
      based. Types of collaborations and stakeholders involved appeared to vary by
      priority.

PMID- 27026686
TI  - Creating Highly Reliable Accountable Care Organizations.
AB  - Accountable Care Organizations' (ACOs) pursuit of the triple aim of higher
      quality, lower cost, and improved population health has met with mixed results.
      To improve the design and implementation of ACOs we look to organizations that
      manage similarly complex, dynamic, and tightly coupled conditions while
      sustaining exceptional performance known as high-reliability organizations. We
      describe the key processes through which organizations achieve reliability, the
      leadership and organizational practices that enable it, and the role that
      professionals can play when charged with enacting it. Specifically, we present
      concrete practices and processes from health care organizations pursuing high
      reliability and from early ACOs to illustrate how the triple aim may be met by
      cultivating mindful organizing, practicing reliability-enhancing leadership, and
      identifying and supporting reliability professionals. We conclude by proposing a
      set of research questions to advance the study of ACOs and high-reliability
      research.

PMID- 27026688
TI  - Association between built environment and moderate to vigorous physical activity
      in Korean adults: a multilevel analysis.
AB  - Background: Research on the association between the built environment and
      moderate and vigorous physical activities (MVPA) is still evolving. Therefore,
      more evidence is needed. This study examines the relationship between built
      environment and MVPA in Korean adults. Methods: A large sample of 204 324 adults
      from the 2012 Korean Community Health Survey (KCHS) was analyzed. MVPA was
      assessed by the International Physical Activity Questionnaire. Individual
      correlates from the KCHS and community built environment data from the Korean
      government were collected. A multilevel logistic regression was performed using
      the GLIMMIX procedure. Results: Residents in cities (OR = 0.75, 95% CI 0.60-0.93)
      and districts (OR = 0.70, 95% CI 0.52-0.94) were less likely to engage in MVPA
      than residents in counties. While residents in communities with the least amount
      of physical equipment were less likely to participate in MVPA (OR = 0.72, 95% CI
      0.57-0.90), residents in communities with the second smallest area of open space
      for PA were more likely to be active (OR = 1.37, 95% CI 1.07-1.77). The effect of
      built environment on MVPA was significant but relatively weak in comparison to
      the influence of individual correlates. Conclusions: To improve MVPA in adults, a
      community built environment should be considered along with individual
      correlates.

PMID- 27026687
TI  - Dissecting the stochastic transcription initiation process in live Escherichia
      coli.
AB  - We investigate the hypothesis that, in Escherichia coli, while the concentration
      of RNA polymerases differs in different growth conditions, the fraction of RNA
      polymerases free for transcription remains approximately constant within a
      certain range of these conditions. After establishing this, we apply a standard
      model-fitting procedure to fully characterize the in vivo kinetics of the rate
      limiting steps in transcription initiation of the Plac/ara-1 promoter from
      distributions of intervals between transcription events in cells with different
      RNA polymerase concentrations. We find that, under full induction, the closed
      complex lasts ~788 s while subsequent steps last ~193 s, on average. We then
      establish that the closed complex formation usually occurs multiple times prior
      to each successful initiation event. Furthermore, the promoter intermittently
      switches to an inactive state that, on average, lasts ~87 s. This is shown to
      arise from the intermittent repression of the promoter by LacI. The methods
      employed here should be of use to resolve the rate-limiting steps governing the
      in vivo dynamics of initiation of prokaryotic promoters, similar to established
      steady-state assays to resolve the in vitro dynamics. 

PMID- 27026689
TI  - Targeting ultrasound remission in early rheumatoid arthritis: the results of the
      TaSER study, a randomised clinical trial.
AB  - OBJECTIVE: To investigate whether an intensive early rheumatoid arthritis (RA)
      treat-to-target (T2T) strategy could be improved through the use of
      musculoskeletal ultrasound (MSUS) assessment of disease activity. METHODS: 111
      newly diagnosed patients with RA or undifferentiated arthritis (symptom duration
      <1 year) were randomised to strategies that aimed to attain either DAS28
      erythrocyte sedimentation rate (ESR)<3.2 (control) or a total power Doppler joint
      count<=1 during a combined DAS28-ESR/MSUS assessment (intervention). MSUS
      examination was indicated if: DAS28-ESR<3.2 or DAS28-ESR>=3.2 with two swollen
      joints. Step-up disease-modifying antirheumatic drug (DMARD) escalation was
      standardised: methotrexate monotherapy, triple therapy and then etanercept/triple
      therapy. American College of Rheumatology (ACR) core-set variables were assessed
      3 monthly by a metrologist blinded to group allocation. MRI of dominant hand and
      wrist, and plain radiographs of hands and feet were undertaken at baseline and 18
      months for grading by two readers using the Outcome Measures in Rheumatology
      (OMERACT) Rheumatoid Arthritis MRI Scoring System (RAMRIS) and van der
      Heijde/Sharp Score, respectively. The coprimary outcomes were mean change from
      baseline of DAS44 and RAMRIS erosion score. RESULTS: Groups were matched for
      baseline clinical, demographic and radiographic features. The intervention group
      received more intensive DMARD therapy. Both groups demonstrated significant
      improvements in DAS44 (mean change: control -2.58, intervention -2.69; 95% CI
      difference between groups -0.70 to 0.48; p=0.72). There were no significant
      between-group differences for any ACR core-set variables, except DAS44 remission
      after 18 months (control 43%, intervention 66%; p=0.03). There was minimal
      progression of MRI and radiographic erosions and no difference in imaging
      outcomes or serious adverse event rates. CONCLUSIONS: In early RA, a MSUS-driven
      T2T strategy led to more intensive treatment, but was not associated with
      significantly better clinical or imaging outcomes than a DAS28-driven strategy.
      TRIAL REGISTRATION NUMBER: NCT00920478.

PMID- 27026690
TI  - Evidence for treating rheumatoid arthritis to target: results of a systematic
      literature search update.

PMID- 27026691
TI  - Evaluation of a Physical Activity Intervention for Adults With Brain Impairment:
      A Controlled Clinical Trial.
AB  - BACKGROUND: Individuals with brain impairment (BI) are less active than the
      general population and have increased risk of chronic disease. OBJECTIVE: This
      controlled trial evaluated the efficacy of a physical activity (PA) intervention
      for community-dwelling adults with BI. METHODS: A total of 43 adults with BI (27
      male, 16 female; age 38.1 +/- 11.9 years; stage of change 1-3) who walked as
      their primary means of locomotion were allocated to an intervention (n = 23) or
      control (n = 20) condition. The intervention comprised 10 face-to-face home
      visits over 12 weeks, including a tailored combination of stage-matched behavior
      change activities, exercise prescription, community access facilitation, and
      relapse prevention strategies. The control group received 10 face-to-face visits
      over 12 weeks to promote sun safety, healthy sleep, and oral health. Primary
      outcomes were daily activity counts and minutes of moderate-to-vigorous-intensity
      PA (MVPA) measured with the ActiGraph GT1M at baseline (0 weeks),
      postintervention (12 weeks) and follow-up (24 weeks). Between-group differences
      were evaluated for statistical significance using repeated-measures ANOVA.
      RESULTS: MVPA for the intervention group increased significantly from baseline to
      12 weeks (20.8 +/- 3.1 to 31.2 +/- 3.1 min/d; P = .01), but differences between
      baseline and 24 weeks were nonsignificant (20.8 +/- 3.1 to 25.3 +/- 3.2 min/d; P
      = .28). MVPA changes for the control group were negligible and nonsignificant.
      Between-group differences for change in MVPA were significant at 12 weeks (P =
      .03) but not at 24 weeks (P = .49). CONCLUSION: The 12-week intervention
      effectively increased adoption of PA in a sample of community-dwelling adults
      with BI immediately after the intervention but not at follow-up. Future studies
      should explore strategies to foster maintenance of PA participation.

PMID- 27026692
TI  - Long-Term Exercise Improves Memory Deficits via Restoration of Myelin and
      Microvessel Damage, and Enhancement of Neurogenesis in the Aged Gerbil
      Hippocampus After Ischemic Stroke.
AB  - BACKGROUND: The positive correlation between therapeutic exercise and memory
      recovery in cases of ischemia has been extensively studied; however, long-term
      exercise begun after ischemic neuronal death as a chronic neurorestorative
      strategy has not yet been thoroughly examined. OBJECTIVE: The purpose of this
      study is to investigate possible mechanisms by which exercise ameliorates
      ischemia-induced memory impairment in the aged gerbil hippocampus after transient
      cerebral ischemia. METHODS: Treadmill exercise was begun 5 days after ischemia
      reperfusion (I-R) and lasted for 1 or 4 weeks. The animals were sacrificed 31
      days after the induction of ischemia. Changes in short-term memory, as well as
      the hippocampal expression of markers of cell proliferation, neuroblast
      differentiation, neurogenesis, myelin and microvessel repair, and growth factors
      were examined by immunohistochemistry and/or western blots. RESULTS: Four weeks
      of exercise facilitated memory recovery despite neuronal damage in the stratum
      pyramidale (SP) of the hippocampal CA1 region and in the polymorphic layer (PoL)
      of the dentate gyrus (DG) after I-R. Long-term exercise enhanced cell
      proliferation and neuroblast differentiation in a time-dependent manner, and
      newly generated mature cells were found in the granule cell layer of the DG, but
      not in the SP of the CA1 region or in the PoL of the DG. In addition, long-term
      exercise ameliorated ischemia-induced damage of myelin and microvessels, which
      was correlated with increased BDNF expression in the CA1 region and the DG.
      CONCLUSIONS: These results suggest that long-term treadmill exercise after I-R
      can restore memory function through replacement of multiple damaged structures in
      the ischemic aged hippocampus.

PMID- 27026693
TI  - Chondrocalcinosis and Gitelman syndrome.

PMID- 27026694
TI  - A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension.

PMID- 27026695
TI  - Hertoghe sign: a hallmark of lepromatous leprosy.

PMID- 27026696
TI  - Cerebral toxoplasmosis.

PMID- 27026697
TI  - Two teachers and a book.

PMID- 27026698
TI  - Cognitive impairment and reduced quality of life among old-age groups in Southern
      Urban India: home-based community residents, free and paid old-age home
      residents.
AB  - AIM: The purpose of the study were (i) to screen for cognitive impairment using
      Mini-Mental Status Examination among three old-age groups based on dwelling types
      in Chennai, India i.e. residential paid old-age homes, residential free
      (charitable) homes and home-based community-dwelling residents; (ii) secondly to
      investigate factors (demographic, psychological, medical and disability)
      associated with cognitive impairment in the these old-age; (iii) third, to
      investigate the independent association between cognitive impairment and health
      related quality of life (QOL) among elderly across aged care dwelling types.
      METHODS: A total of 499 elderly from three old-age groups were interviewed in
      this cross-sectional study (173 elderly home-based community-dwellers, 176 paid
      home and 150 free-home residents). All the participants were interviewed for
      their socio-economic condition, medical morbidity, self-reported worry and
      anxiety, disability and QOL. RESULTS: 42.7% free-home elderly residents were
      found to have cognitive impairment, whereas 32.4% of paid-home and 21.9% of
      community-dwelling elderly had cognitive impairment. The residents of free-home
      were less educated, had lower income and reported higher incidence of worry,
      anxiety, disability and poor QOL than community-dwelling or paid-home residents.
      Increasing age, low education, female gender, high blood pressure and disability
      were associated with cognitive impairment. Cognitive impairment had significant
      negative effect on their health-related QOL (b = -0.10, P = 0.01), independent of
      age, gender, education, chronic illness and dwelling type. CONCLUSION: The burden
      of cognitive impairment was high in all aged-care dwelling types in urban India;
      with free charitable home residents being worse affected. Cognitive impairment
      was associated with disability and poor health-related QOL in these age-care
      settings.

PMID- 27026699
TI  - Associations between heart failure and physical function in US adults.
AB  - BACKGROUND: There is a paucity of nationally representative data in the area of
      heart failure (HF) and physical function (PF). AIM: Examine the relationship(s)
      between HF and PF in a nationally representative sample of United States (US)
      adults. DESIGN: Cross-section analysis of US adults. METHODS: Sample (n = 6623)
      included adult (>=40 years of age) participants from the 1999-2006 National
      Health and Nutrition Examination Survey. Participants reporting HF answered
      questions related to their abilities to accomplish specific upper extremity and
      lower extremity tasks, and household chores. RESULTS: Prevalence estimates of
      reporting much difficulty or the inability to stand from an armless chair was
      9.9% and 4.3% (P = 0.002) in those with and without HF, respectively. Similar
      estimates were revealed for much difficulty or inability to lift or carry 10
      pounds (16.8% and 8.6%, P = 0.0004) and much difficulty or inability to do
      household chores (13.3% and 6.1%, P = 0.0008). Following adjustments participants
      reporting HF had significantly greater odds of reporting much difficulty or the
      inability to stand from an armless chair [odds ratio (OR) 1.93; 95% confidence
      intervals (CI) 1.25, 2.96], much difficulty or the inability to lift or carry 10
      lbs (OR 1.90; 95% CI 1.36, 2.65) and much difficulty or inability to do household
      chores (OR 2.06; 95% CI 1.41, 3.02) compared with participants not reporting HF.
      CONCLUSIONS: Findings suggest US adults reporting HF are more likely to report
      poorer PF.

PMID- 27026700
TI  - DNA Instability Maintains the Repeat Length of the Yeast RNA Polymerase II C
      terminal Domain.
AB  - The C-terminal domain (CTD) of RNA polymerase II in eukaryotes is comprised of
      tandemly repeating units of a conserved seven-amino acid sequence. The number of
      repeats is, however, quite variable across different organisms. Furthermore,
      previous studies have identified evidence of rearrangements within the CTD coding
      region, suggesting that DNA instability may play a role in regulating or
      maintaining CTD repeat number. The work described here establishes a clear
      connection between DNA instability and CTD repeat number in Saccharomyces
      cerevisiae First, analysis of 36 diverse S. cerevisiae isolates revealed evidence
      of numerous past rearrangements within the DNA sequence that encodes the CTD.
      Interestingly, the total number of CTD repeats was relatively static (24-26
      repeats in all strains), suggesting a balancing act between repeat expansion and
      contraction. In an effort to explore the genetic plasticity within this region,
      we measured the rates of repeat expansion and contraction using novel reporters
      and a doxycycline-regulated expression system for RPB1 In efforts to determine
      the mechanisms leading to CTD repeat variability, we identified the presence of
      DNA secondary structures, specifically G-quadruplex-like DNA, within the CTD
      coding region. Furthermore, we demonstrated that mutating PIF1, a G-quadruplex
      specific helicase, results in increased CTD repeat length polymorphisms. We also
      determined that RAD52 is necessary for CTD repeat expansion but not contraction,
      identifying a role for recombination in repeat expansion. Results from these DNA
      rearrangements may help explain the CTD copy number variation seen across
      eukaryotes, as well as support a model of CTD expansion and contraction to
      maintain CTD integrity and overall length.

PMID- 27026701
TI  - Development of a MUO-Conotoxin Analogue with Improved Lipid Membrane Interactions
      and Potency for the Analgesic Sodium Channel NaV1.8.
AB  - The MUO-conotoxins MrVIA, MrVIB, and MfVIA inhibit the voltage-gated sodium
      channel NaV1.8, a well described target for the treatment of pain; however,
      little is known about the residues or structural elements that define this
      activity. In this study, we determined the three-dimensional structure of MfVIA,
      examined its membrane binding properties, performed alanine-scanning mutagenesis,
      and identified residues important for its activity at human NaV1.8. A second
      round of mutations resulted in (E5K,E8K)MfVIA, a double mutant with greater
      positive surface charge and greater affinity for lipid membranes compared with
      MfVIA. This analogue had increased potency at NaV1.8 and was analgesic in the
      mouse formalin assay.

PMID- 27026702
TI  - A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal
      Migration during Brain Development.
AB  - Disturbance of neuronal migration may cause various neurological disorders. Both
      the transforming growth factor-beta (TGF-beta) signaling and microcephaly
      associated protein WDR62 are important for neuronal migration during brain
      development; however, the underlying molecular mechanisms involved remain
      unclear. We show here that knock-out or knockdown of Tak1 (TGFbeta-activated
      kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during
      cortical development and that the migration defects incurred by knock-out and/or
      knockdown of Tbetar2 (type II TGF-beta receptor) or Tak1 can be partially rescued
      by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein
      complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly
      associated protein WDR62 and the RAC1-interacting protein POSH (plenty of Src
      homology). Components of the complex coordinate with each other in the regulation
      of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes
      are involved in the diversified biological and pathological functions during
      brain development and pathogenesis of diseases.

PMID- 27026703
TI  - The Structure of the Complex between Yeast Frataxin and Ferrochelatase:
      CHARACTERIZATION AND PRE-STEADY STATE REACTION OF FERROUS IRON DELIVERY AND HEME
      SYNTHESIS.
AB  - Frataxin is a mitochondrial iron-binding protein involved in iron storage,
      detoxification, and delivery for iron sulfur-cluster assembly and heme
      biosynthesis. The ability of frataxin from different organisms to populate
      multiple oligomeric states in the presence of metal ions, e.g. Fe(2+) and Co(2+),
      led to the suggestion that different oligomers contribute to the functions of
      frataxin. Here we report on the complex between yeast frataxin and
      ferrochelatase, the terminal enzyme of heme biosynthesis. Protein-protein docking
      and cross-linking in combination with mass spectroscopic analysis and single
      particle reconstruction from negatively stained electron microscopic images were
      used to verify the Yfh1-ferrochelatase interactions. The model of the complex
      indicates that at the 2:1 Fe(2+)-to-protein ratio, when Yfh1 populates a trimeric
      state, there are two interaction interfaces between frataxin and the
      ferrochelatase dimer. Each interaction site involves one ferrochelatase monomer
      and one frataxin trimer, with conserved polar and charged amino acids of the two
      proteins positioned at hydrogen-bonding distances from each other. One of the
      subunits of the Yfh1 trimer interacts extensively with one subunit of the
      ferrochelatase dimer, contributing to the stability of the complex, whereas
      another trimer subunit is positioned for Fe(2+) delivery. Single-turnover stopped
      flow kinetics experiments demonstrate that increased rates of heme production
      result from monomers, dimers, and trimers, indicating that these forms are most
      efficient in delivering Fe(2+) to ferrochelatase and sustaining porphyrin
      metalation. Furthermore, they support the proposal that frataxin-mediated
      delivery of this potentially toxic substrate overcomes formation of reactive
      oxygen species.

PMID- 27026704
TI  - Substrate Recognition and Activity Regulation of the Escherichia coli mRNA
      Endonuclease MazF.
AB  - Escherichia coli MazF (EcMazF) is the archetype of a large family of
      ribonucleases involved in bacterial stress response. The crystal structure of
      EcMazF in complex with a 7-nucleotide substrate mimic explains the relaxed
      substrate specificity of the E. coli enzyme relative to its Bacillus subtilis
      counterpart and provides a framework for rationalizing specificity in this enzyme
      family. In contrast to a conserved mode of substrate recognition and a conserved
      active site, regulation of enzymatic activity by the antitoxin EcMazE diverges
      from its B. subtilis homolog. Central in this regulation is an EcMazE-induced
      double conformational change as follows: a rearrangement of a crucial active site
      loop and a relative rotation of the two monomers in the EcMazF dimer. Both are
      induced by the C-terminal residues Asp-78-Trp-82 of EcMazE, which are also
      responsible for strong negative cooperativity in EcMazE-EcMazF binding. This
      situation shows unexpected parallels to the regulation of the F-plasmid CcdB
      activity by CcdA and further supports a common ancestor despite the different
      activities of the MazF and CcdB toxins. In addition, we pinpoint the origin of
      the lack of activity of the E24A point mutant of EcMazF in its inability to
      support the substrate binding-competent conformation of EcMazF. 

PMID- 27026705
TI  - Poly(ADP-ribose) Polymerase 1 Represses Liver X Receptor-mediated ABCA1
      Expression and Cholesterol Efflux in Macrophages.
AB  - Liver X receptors (LXR) are oxysterol-activated nuclear receptors that play a
      central role in reverse cholesterol transport through up-regulation of ATP
      binding cassette transporters (ABCA1 and ABCG1) that mediate cellular cholesterol
      efflux. Mouse models of atherosclerosis exhibit reduced atherosclerosis and
      enhanced regression of established plaques upon LXR activation. However, the
      coregulatory factors that affect LXR-dependent gene activation in macrophages
      remain to be elucidated. To identify novel regulators of LXR that modulate its
      activity, we used affinity purification and mass spectrometry to analyze nuclear
      LXRalpha complexes and identified poly(ADP-ribose) polymerase-1 (PARP-1) as an
      LXR-associated factor. In fact, PARP-1 interacted with both LXRalpha and LXRbeta.
      Both depletion of PARP-1 and inhibition of PARP-1 activity augmented LXR ligand
      induced ABCA1 expression in the RAW 264.7 macrophage line and primary bone marrow
      derived macrophages but did not affect LXR-dependent expression of other target
      genes, ABCG1 and SREBP-1c. Chromatin immunoprecipitation experiments confirmed
      PARP-1 recruitment at the LXR response element in the promoter of the ABCA1 gene.
      Further, we demonstrated that LXR is poly(ADP-ribosyl)ated by PARP-1, a potential
      mechanism by which PARP-1 influences LXR function. Importantly, the PARP
      inhibitor 3-aminobenzamide enhanced macrophage ABCA1-mediated cholesterol efflux
      to the lipid-poor apolipoprotein AI. These findings shed light on the important
      role of PARP-1 on LXR-regulated lipid homeostasis. Understanding the interplay
      between PARP-1 and LXR may provide insights into developing novel therapeutics
      for treating atherosclerosis. 

PMID- 27026706
TI  - Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the
      Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as
      a Steroid-binding Protein.
AB  - Corticosteroid-binding globulin (CBG) was isolated from chicken serum and
      identified by mass spectrometry and genomic analysis. This revealed that the
      organization and synteny of avian and mammalian SerpinA6 genes are conserved.
      Recombinant zebra finch CBG steroid-binding properties reflect those of the
      natural protein in plasma and confirm its identity. Zebra finch and rat CBG
      crystal structures in complex with cortisol resemble each other, but their
      primary structures share only ~40% identity, and their steroid-binding site
      topographies differ in several unexpected ways. Remarkably, a tryptophan that
      anchors ligands in mammalian CBG steroid-binding sites is replaced by an
      asparagine. Phylogenetic comparisons show that reptilian CBG orthologs share this
      unexpected property. Glycosylation of this asparagine in zebra finch CBG does not
      influence its steroid-binding affinity, but we present evidence that it may
      participate in protein folding and steroid-binding site formation. Substitutions
      of amino acids within zebra finch CBG that are conserved only in birds reveal how
      they contribute to their distinct steroid-binding properties, including their
      high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. As
      in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra
      finch plasma within its reactive center loop and disrupts steroid binding,
      suggesting an evolutionarily conserved property of CBGs. Measurements of CBG mRNA
      in zebra finch tissues indicate that liver is the main site of plasma CBG
      production, and anti-zebra finch CBG antibodies cross-react with CBGs in other
      birds, extending opportunities to study how CBG regulates the actions of
      glucocorticoids and sex steroids in these species. 

PMID- 27026707
TI  - The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen
      Receptor Activity and Stimulates Novel Phosphoproteomic Signatures.
AB  - Estrogen exerts cellular effects through both nuclear (ESR1 and ESR2) and
      membrane-bound estrogen receptors (G-protein coupled estrogen receptor, GPER);
      however, it is unclear if they act independently or engage in crosstalk to
      influence hormonal responses. To investigate each receptor's role in
      proliferation, transcriptional activation, and protein phosphorylation in breast
      cancer cells (MCF-7), we employed selective agonists for ESR1 propyl-pyrazole
      triol (PPT), ESR2 diarylpropionitrile (DPN), and GPER (G-1) and also determined
      the impact of xenoestrogens bisphenol-A (BPA) and genistein on these effects. As
      anticipated, 17beta-estradiol (E2), PPT, DPN, BPA, and genistein each enhanced
      proliferation and activation of an ERE-driven reporter gene whereas G-1 had no
      significant impact. However, G-1 significantly reduced E2-, PPT-, DPN-, BPA-, and
      genistein-induced proliferation and ERE activation at doses greater than 500 nM
      indicating that G-1 mediated inhibition is not ESR isotype specific. As membrane
      receptors initiate cascades of phosphorylation events, we performed a global
      phosphoproteomic analysis on cells exposed to E2 or G-1 to identify potential
      targets of receptor crosstalk via downstream protein phosphorylation targets. Of
      the 211 phosphorylated proteins identified, 40 and 13 phosphoproteins were
      specifically modified by E2 and G-1, respectively. Subnetwork enrichment analysis
      revealed several processes related to cell cycle were specifically enriched by G
      1 compared with E2. Further there existed a number of newly identified proteins
      that were specifically phosphorylated by G-1. These phosphorylation networks
      highlight specific proteins that may modulate the inhibitory effects of G-1 and
      suggest a novel role for interference with nuclear receptor activity driven by E2
      and xenoestrogens.

PMID- 27026708
TI  - Grouping 34 Chemicals Based on Mode of Action Using Connectivity Mapping.
AB  - Connectivity mapping is a method used in the pharmaceutical industry to find
      connections between small molecules, disease states, and genes. The concept can
      be applied to a predictive toxicology paradigm to find connections between
      chemicals, adverse events, and genes. In order to assess the applicability of the
      technique for predictive toxicology purposes, we performed gene array experiments
      on 34 different chemicals: bisphenol A, genistein, ethinyl-estradiol, tamoxifen,
      clofibrate, dehydorepiandrosterone, troglitazone, diethylhexyl phthalate,
      flutamide, trenbolone, phenobarbital, retinoic acid, thyroxine, 1alpha,25
      dihydroxyvitamin D3, clobetasol, farnesol, chenodeoxycholic acid, progesterone,
      RU486, ketoconazole, valproic acid, desferrioxamine, amoxicillin, 6
      aminonicotinamide, metformin, phenformin, methotrexate, vinblastine, ANIT (1
      naphthyl isothiocyanate), griseofulvin, nicotine, imidacloprid, vorinostat,
      2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) at the 6-, 24-, and 48-hour time
      points for 3 different concentrations in the 4 cell lines: MCF7, Ishikawa,
      HepaRG, and HepG2 GEO (super series accession no.: GSE69851). The 34 chemicals
      were grouped in to predefined mode of action (MOA)-based chemical classes based
      on current literature. Connectivity mapping was used to find linkages between
      each chemical and between chemical classes. Cell line-specific linkages were
      compared with each other and to test whether the method was platform and user
      independent, a similar analysis was performed against publicly available data.
      The study showed that the method can group chemicals based on MOAs and the inter
      chemical class comparison alluded to connections between MOAs that were not
      predefined. Comparison to the publicly available data showed that the method is
      user and platform independent. The results provide an example of an alternate
      data analysis process for high-content data, beneficial for predictive
      toxicology, especially when grouping chemicals for read across purposes.

PMID- 27026709
TI  - Linking Inflammation and Parkinson Disease: Hypochlorous Acid Generates
      Parkinsonian Poisons.
AB  - Inflammation is a common feature of Parkinson Disease and other neurodegenerative
      disorders. Hypochlorous acid (HOCl) is a reactive oxygen species formed by
      neutrophils and other myeloperoxidase-containing cells during inflammation. HOCl
      chlorinates the amine and catechol moieties of dopamine to produce chlorinated
      derivatives collectively termed chlorodopamine. Here, we report that
      chlorodopamine is toxic to dopaminergic neurons both in vivo and in vitro
      Intrastriatal administration of 90 nmol chlorodopamine to mice resulted in loss
      of dopaminergic neurons from the substantia nigra and decreased ambulation
      results that were comparable to those produced by the same dose of the
      parkinsonian poison, 1-methyl-4-phenylpyridinium (MPP+). Chlorodopamine was also
      more toxic to differentiated SH SY5Y cells than HOCl. The basis of this selective
      toxicity is likely mediated by chlorodopamine uptake through the dopamine
      transporter, as expression of this transporter in COS-7 cells conferred
      sensitivity to chlorodopamine toxicity. Pharmacological blockade of the dopamine
      transporter also mitigated the deleterious effects of chlorodopamine in vivo The
      cellular actions of chlorodopamine included inactivation of the alpha
      ketoglutarate dehydrogenase complex, as well as inhibition of mitochondrial
      respiration. The latter effect is consistent with inhibition of cytochrome c
      oxidase. Illumination at 670 nm, which stimulates cytochrome c oxidase, reversed
      the effects of chlorodopamine. The observed changes in mitochondrial biochemistry
      were also accompanied by the swelling of these organelles. Overall, our findings
      suggest that chlorination of dopamine by HOCl generates toxins that selectively
      kill dopaminergic neurons in the substantia nigra in a manner comparable to MPP+.

PMID- 27026710
TI  - Rat Urinary Osteopontin and Neutrophil Gelatinase-Associated Lipocalin Improve
      Certainty of Detecting Drug-Induced Kidney Injury.
AB  - Traditional kidney biomarkers are insensitive indicators of acute kidney injury,
      with meaningful changes occurring late in the course of injury. The aim of this
      work was to demonstrate the diagnostic potential of urinary osteopontin (OPN) and
      neutrophil gelatinase-associated lipocalin (NGAL) for drug-induced kidney injury
      (DIKI) in rats using data from a recent regulatory qualification submission of
      translational DIKI biomarkers and to compare performance of NGAL and OPN to five
      previously qualified DIKI urinary biomarkers. Data were compiled from 15 studies
      of 11 different pharmaceuticals contributed by Critical Path Institute's
      Predictive Safety Testing Consortium (PSTC) Nephrotoxicity Working Group (NWG).
      Rats were given doses known to cause DIKI or other target organ toxicity, and
      urinary levels of the candidate biomarkers were assessed relative to kidney
      histopathology and serum creatinine (sCr) and blood urea nitrogen (BUN).OPN and
      NGAL outperformed sCr and BUN in identifying DIKI manifested as renal tubular
      epithelial degeneration or necrosis. In addition, urinary OPN and NGAL, when used
      with sCr and BUN, increased the ability to detect renal tubular epithelial
      degeneration or necrosis. NGAL and OPN had comparable or improved performance
      relative to Kim-1, clusterin, albumin, total protein, and beta-2 microglobulin.
      Given these data, both urinary OPN and NGAL are appropriate for use with current
      methods for assessing nephrotoxicity to identify and monitor DIKI in regulatory
      toxicology studies in rats. These data also support exploratory use of urinary
      OPN and NGAL in safety monitoring strategies of early clinical trials to aid in
      the assurance of patient safety.

PMID- 27026711
TI  - Why a new algorithm using high-sensitivity cardiac troponins for the rapid rule
      out of NSTEMI is not adapted to routine practice.

PMID- 27026712
TI  - Recent progress towards understanding the role of DNA methylation in human
      placental development.
AB  - Epigenetic modifications, and particularly DNA methylation, have been studied in
      many tissues, both healthy and diseased, and across numerous developmental
      stages. The placenta is the only organ that has a transient life of 9 months and
      undergoes rapid growth and dynamic structural and functional changes across
      gestation. Additionally, the placenta is unique because although developing
      within the mother, its genome is identical to that of the foetus. Given these
      distinctive characteristics, it is not surprising that the epigenetic landscape
      affecting placental gene expression may be different to that in other healthy
      tissues. However, the role of epigenetic modifications, and particularly DNA
      methylation, in placental development remains largely unknown. Of particular
      interest is the fact that the placenta is the most hypomethylated human tissue
      and is characterized by the presence of large partially methylated domains (PMDs)
      containing silenced genes. Moreover, how and why the placenta is hypomethylated
      and what role DNA methylation plays in regulating placental gene expression
      across gestation are poorly understood. We review genome-wide DNA methylation
      studies in the human placenta and highlight that the different cell types that
      make up the placenta have very different DNA methylation profiles. Summarizing
      studies on DNA methylation in the placenta and its relationship with pregnancy
      complications are difficult due to the limited number of studies available for
      comparison. To understand the key steps in placental development and hence what
      may be perturbed in pregnancy complications requires large-scale genome-wide DNA
      methylation studies coupled with transcriptome analyses.

PMID- 27026713
TI  - Molecular cues to the anti-implantation effect of nano-puerarin in rats.
AB  - Puerarin, a selective oestrogen receptor modulator, intercepts implantation in
      rats, albeit at unacceptably higher doses. We developed poly lactic-co-glycolic
      acid-encapsulated nano-puerarin (PN) and mapped the molecular pathway underlying
      its anti-implantation effects. Smooth-surfaced and spherical PN having a mean
      diameter of ~147nm was obtained with good yield, efficient encapsulation, and
      optimum drug loading. In culture, PN slowly and steadily released puerarin, which
      was readily taken up by the decidual cells. PN exerted a dose-dependent anti
      implantation effect. As marked by attenuated expression of stromal cell desmin,
      alkaline phosphatase, IGFBP1, and decidual prolactin-related protein, the anti
      implantation effect of PN seemed secondary to compromised decidualization. Using
      in vivo (pregnant and pseudopregnant rats) and in vitro (endometrial stromal cell
      culture) treatment models, we document that PN enforced inhibition of uterine
      expression of Hbegf and Hoxa10 and their downstream signalling molecules, Cyclin
      D3 (CCND3)/CDK4. PN also efficiently ablated the Ihh-Nr2f2-Bmp2 signalling
      pathway and invited the loss of uterine potential for decidualization. There was
      a dose-dependent up-regulation of RHOA and its effector protein kinase, ROCK1,
      leading to the promotion of MLC phosphorylation and actin-myosin interaction. PN
      also down-regulated the stromal cell activation of ERK1/2 and expression of MMP9.
      These effects acting together stabilized the stroma and inhibited the stromal
      cell migration. Central to this array of events was the adversely altered
      endometrial expression of oestrogen receptor subtypes and repression of
      progesterone receptor that indulged endless proliferation of luminal epithelia
      and distorted the precisely choreographed stroma-epithelia crosstalk. Thus, PN
      dismantles the endometrial bed preparation and prevents implantation.

PMID- 27026714
TI  - Sex-specific prenatal stress effects on the rat reproductive axis and adrenal
      gland structure.
AB  - Social stress during pregnancy has profound effects on offspring physiology. This
      study examined whether an ethologically relevant social stress during late
      pregnancy in rats alters the reproductive axis and adrenal gland structure in
      post-pubertal male and female offspring. Prenatally stressed (PNS) pregnant rats
      (n=9) were exposed to an unfamiliar lactating rat for 10 min/day from day 16 to
      20 of pregnancy inclusive, whereas control pregnant rats (n=9) remained in their
      home cages. Gonads, adrenal glands and blood samples were obtained from one
      female and one male from each litter at 11 to 12-weeks of age. Anogenital
      distance was measured. There was no treatment effect on body, adrenal or gonad
      weight at 11-12 weeks. PNS did not affect the number of primordial, secondary or
      tertiary ovarian follicles, numbers of corpora lutea or ovarian FSH receptor
      expression. There was an indication that PNS females had more primary follicles
      and greater ovarian aromatase expression compared with control females (both
      P=0.09). PNS males had longer anogenital distances (0.01+/-0.0 cm/g vs 0.008+/
      0.00 cm/g; P=0.007) and higher plasma FSH concentrations (0.05 ng/mL vs 0.006
      ng/mL; s.e.d.=0.023; P=0.043) compared with control males. There were no
      treatment effects on the number of Sertoli cells or seminiferous tubules,
      seminiferous tubule area, plasma testosterone concentration or testis expression
      of aromatase, FSH receptor or androgen receptor. PNS did not affect adrenal size.
      These data suggest that the developing male reproductive axis is more sensitive
      to maternal stress and that PNS may enhance aspects of male reproductive
      development.

PMID- 27026715
TI  - The magnetic orientation of the Antarctic amphipod Gondogeneia antarctica is
      cancelled by very weak radiofrequency fields.
AB  - Studies on weak man-made radiofrequency (RF) electromagnetic fields affecting
      animal magnetoreception aim for a better understanding of the reception mechanism
      and also point to a new phenomenon having possible consequences in ecology and
      environmental protection. RF impacts on magnetic compasses have recently been
      demonstrated in migratory birds and other vertebrates. We set out to investigate
      the effect of RF on the magnetic orientation of the Antarctic krill species
      Gondogeneia antarctica, a small marine crustacean widespread along the Antarctic
      littoral line. Here, we show that upon release, G. antarctica (held under
      laboratory conditions) escaped in the magnetically seaward direction along the
      magnetic sea-land axis (y-axis) of the home beach. However, the animals were
      disoriented after being exposed to RF. Orientation was lost not only in an RF
      field with a magnetic flux density of 20 nT, as expected according to the
      literature, but even under the 2 nT originally intended as a control. Our results
      extend recent findings of the extraordinary sensitivity of animal
      magnetoreception to weak RF fields in marine invertebrates.

PMID- 27026716
TI  - Intraspecific variation in physiological performance of a benthic elasmobranch
      challenged by ocean acidification and warming.
AB  - Elucidating the combined effects of increasing temperature and ocean
      acidification on performance of fishes is central to our understanding of how
      species will respond to global climate change. Measuring the metabolic costs
      associated with intense and short activities, such as those required to escape
      predators, is key to quantifying changes in performance and estimating the
      potential effects of environmental stressors on survival. In this study, juvenile
      little skate Leucoraja erinacea from two neighboring locations (Gulf of Maine, or
      northern location, and Georges Bank, or southern location) were developmentally
      acclimatized and reared at current and projected temperatures (15, 18 or 20
      degrees C) and acidification conditions (pH 8.1 or 7.7), and their escape
      performance was tested by employing a chasing protocol. The results from this
      study suggest countergradient variation in growth between skates from the two
      locations, while the optimum for escape performance was at a lower temperature in
      individuals from the northern latitudes, which could be related to adaptation to
      the local thermal environment. Aerobic performance and scope declined in skates
      from the northern latitudes under simulated ocean warming and acidification
      conditions. Overall, the southern skates showed lower sensitivity to these
      climatic stressors. This study demonstrates that even mobile organisms from
      neighboring locations can exhibit substantial differences in energetic costs of
      exercise and that skates from the northern part of the geographic range may be
      more sensitive to the directional increase in temperature and acidification
      expected by the end of the century.

PMID- 27026717
TI  - In vitro evidence supports the presence of glucokinase-independent glucosensing
      mechanisms in hypothalamus and hindbrain of rainbow trout.
AB  - We previously obtained evidence in rainbow trout for the presence and response to
      changes in circulating levels of glucose (induced by intraperitoneal
      hypoglycaemic and hyperglycaemic treatments) of glucosensing mechanisms based on
      liver X receptor (LXR), mitochondrial production of reactive oxygen species (ROS)
      leading to increased expression of uncoupling protein 2 (UCP2), and sweet taste
      receptor in the hypothalamus, and on sodium/glucose co-transporter 1 (SGLT-1) in
      hindbrain. However, these effects of glucose might be indirect. Therefore, we
      evaluated the response of parameters related to these glucosensing mechanisms in
      a first experiment using pooled sections of hypothalamus and hindbrain incubated
      for 6 h at 15 degrees C in modified Hanks' medium containing 2, 4 or 8 mmol l(-1)
      d-glucose. The responses observed in some cases were consistent with glucosensing
      capacity. In a second experiment, pooled sections of hypothalamus and hindbrain
      were incubated for 6 h at 15 degrees C in modified Hanks' medium with 8 mmol l(
      1) d-glucose alone (control) or containing 1 mmol l(-1) phloridzin (SGLT-1
      antagonist), 20 umol l(-1) genipin (UCP2 inhibitor), 1 umol l(-1) trolox (ROS
      scavenger), 100 umol l(-1) bezafibrate (T1R3 inhibitor) and 50 umol l(-1) geranyl
      geranyl pyrophosphate (LXR inhibitor). The response observed in the presence of
      these specific inhibitors/antagonists further supports the proposal that critical
      components of the different glucosensing mechanisms are functioning in rainbow
      trout hypothalamus and hindbrain.

PMID- 27026718
TI  - Occupational therapy and engineering: Being better together.

PMID- 27026720
TI  - The acquisition of parenting occupations in neonatal intensive care: A
      preliminary perspective.
AB  - BACKGROUND: The birth of a preterm infant represents a major crisis for parents
      that may impact their performance of parenting occupations. PURPOSE: The purpose
      of the study was to explore the experiences that enable parents to participate in
      occupations associated with the role of parenting in a neonatal intensive care
      unit (NICU). METHOD: A paradigmatic analysis of narratives was completed based on
      interviews conducted with six parents of preterm infants. FINDINGS: Six themes
      were identified: anticipating occupations versus reality, needing emotional
      resilience, working to reclaim the parental role, navigating the NICU occupation
      environment transactions, building and maintaining relationships with staff, and
      revisioning the future. IMPLICATIONS: The use of an occupation-based approach
      moves parents' involvement in the NICU beyond basic caregiving occupations. It
      highlights the importance of providing opportunities for nurturing and caring for
      their infants in ways that are meaningful to their identity as a parent.

PMID- 27026721
TI  - [Translation and validation of the Life Balance Inventory: An occupational
      therapy questionnaire].
AB  - BACKGROUND: Despite the interest in the concept of life balance, no questionnaire
      is currently available in French to measure it well. PURPOSE: This study aimed to
      translate the Life Balance Inventory (Objective 1) and to verify the convergent
      validity of the French version (Objective 2). METHOD: A cross-cultural validation
      was first carried out, followed by a cross-sectional descriptive study, with 152
      adults ages 40 and over, with and without physical disabilities. Questionnaires
      were used to measure the following variables, life balance, stress, health, and
      quality of life. RESULTS: A better life balance is associated with a lower degree
      of stress (r = -.36; p < .01) as well as higher physical health (r = .42; p =
      .01), mental health (r = .36; p = .01), and quality of life (r = .54; p < .01).
      IMPLICATIONS: The French version of the Life Balance Inventory is a valid
      questionnaire to assist occupational therapists when assessing time use of their
      clients.

PMID- 27026722
TI  - Self-regulation workshop and Occupational Performance Coaching with teachers: A
      pilot study.
AB  - BACKGROUND: Teachers' occupational role and performance can be undermined when
      working with students with disruptive classroom behaviours. PURPOSE: This pilot
      study aimed to explore the impact of school-based occupational therapy
      intervention on teachers' classroom management self-efficacy and perceived
      performance/satisfaction in their management of students with disruptive
      behaviours. METHOD: This pilot study used a multiple-case replication study
      design. A cohort of regular classroom elementary school teachers (n = 11)
      participated in a 1-day workshop on sensorimotor strategies for supporting
      student self-regulation followed by eight individual sessions of Occupational
      Performance Coaching (OPC). Measurement tools were the Canadian Occupational
      Performance Measure, Goal Attainment Scaling (GAS), and Teachers' Self-Efficacy
      Scale-Classroom Management. FINDINGS: Improvement in teachers' perception of
      performance, satisfaction, and classroom management was seen. GAS showed
      clinically significant improvement. Improvements were sustained at 7 weeks follow
      up. IMPLICATIONS: Preliminary results support the use of sensorimotor education
      combined with OPC to enable teachers' occupational performance.

PMID- 27026723
TI  - Reproducibility of the Sputum Color Evaluation Depends on the Category of
      Caregivers.
AB  - BACKGROUND: Sputum production and purulence were proposed as criteria for
      justifying the use of antimicrobial agents. The Sputum Color Chart was developed
      and validated to standardize purulence of sputum evaluation. The aim of this
      study was to observe the reproducibility of the Sputum Color Chart from different
      categories of health caregivers. METHODS: The color of 10 sputum samples was
      evaluated using photographs for intra- and inter-reliability. The observation was
      repeated 3 times. Eighteen volunteers from 6 categories of health caregivers
      (student in physiotherapy, senior chest physiotherapist, junior resident in
      pulmonology, medical microbiologist, pulmonologist, and general practitioner)
      were investigated. RESULTS: Poor inter-rater reliability was observed for all
      categories with the exception of senior chest physiotherapists. The best intra
      rater reliability was observed for microbiologists and senior chest
      physiotherapists. We found a great proportion (>40%) of important discrepancies
      in 2 categories (junior pulmonologist and general practitioner). The proportion
      of non-discrepancy between evaluators varied between 10 and 40%, depending on the
      category. CONCLUSIONS: Even if the Sputum Color Chart is a useful tool for the
      clinician in the context of clinical deterioration, it presents non-uniform
      reliability regarding the caregivers and their category.

PMID- 27026724
TI  - Minireview: Prognostic factors and the response to hydroxurea treatment in sickle
      cell disease.
AB  - This review describes current considerations in the use of hydroxyurea for the
      management of sickle cell disease in the context of clinical severity. Randomized
      trials of hydroxyurea have generally enrolled subjects with increased severity
      based on frequent vaso-occlusive events. An exception was the BABY HUG study in
      infants which documented substantial benefit even for asymptomatic subjects.
      Increasing data indicate that hydroxyurea has a substantial effect on reducing
      mortality in both adults and children-perhaps the most compelling reason for
      advocating the drug's widespread use. Although the efficacy of hydroxyurea is
      mediated primarily through increased erythrocyte fetal hemoglobin and much has
      been learned about the genomic influences on fetal hemoglobin levels in sickle
      cell disease, our ability to predict the fetal hemoglobin response to hydroxyurea
      remains limited; much more work in this area is indicated. The review is
      concluded with the recommendations of the 2014 NIH Evidence-Based Management of
      Sickle Cell Disease Expert Panel Report. 

PMID- 27026725
TI  - Original Research: Diametric effects of hypoxia on pathophysiology of sickle cell
      disease in a murine model.
AB  - Hypoxia causes erythrocyte sickling in vitro; however, its role in the
      pathophysiology of sickle cell disease is poorly understood. We report that
      hypoxia rapidly decreased oxygen saturation in transgenic sickle cell disease
      mice, but this effect was immediately buffered by a robust ventilatory response.
      The initial hypoxemia improved steadily throughout the duration of hypoxia
      without any detectable acute pulmonary adverse effect. Furthermore, the mice
      suffered acute anemia that ironically was associated with lowering of both plasma
      hemoglobin and heme. These results were corroborated by increased plasma
      haptoglobin and hemopexin levels. Markers of ischemic tissue injury increased
      spatiotemporally following repeated hypoxia exposures. This variation was
      supported by organ-specific induction of hypoxia-responsive genes. Our results
      show that hypoxia exerts diametric effects on sickle cell disease by promoting
      ischemic injury while enhancing the expression of hemolysis scavenger molecules.
      This phenomenon may help to understand the disparate clinical syndromes
      associated with hemolysis and vaso-occlusion in sickle cell disease.

PMID- 27026726
TI  - Eosinophilic granulomatosis with polyangiitis in childhood: retrospective
      experience from a tertiary referral centre in the UK.
AB  - OBJECTIVE: To describe the presenting clinical features, treatment and outcome in
      children with eosinophilic granulomatosis with polyangiitis (EGPA) and to define
      factors that predicted mortality. METHODS: A retrospective case notes review of
      patients fulfilling the Chapel Hill Consensus Conference definition and/or ACR
      criteria for EGPA seen at Great Ormond Street Hospital, London. Demographics,
      clinical features, histopathology, treatment and outcomes were recorded.
      Descriptive statistics were expressed as median and range. Fisher's exact test
      was used for group comparisons. The Paediatric Vasculitis Activity Score and
      Paediatric Vasculitis Damage Index (PVDI) were calculated. RESULTS: Thirteen
      children (38% female) aged at diagnosis 14.1 (4-15.6) years were identified. The
      median time to diagnosis was 2 (0-7.3) years. History of asthma was documented in
      76%. The most common presenting features were pulmonary (69%), skin (61%),
      gastrointestinal (46%), cardiac involvement (46%), paranasal sinus abnormality
      (38%), arthritis/arthralgia (38%) and neurological involvement (15%). Paediatric
      Vasculitis Activity Score at presentation was 8/63 (2-25/63); ANCA was negative
      in all 10/13 patients tested. Treatment included corticosteroids in all, combined
      with CYC in 38% or AZA in 23%. PVDI at 12 (3-48) months follow-up was 3/72 (0
      13/72). Relapses were recorded in 46%. Mortality was 15%; cardiomyopathy and PVDI
      scores ?5 significantly associated with mortality risk (P = 0.012). CONCLUSION:
      EGPA in the paediatric population is a rare and potentially life-threatening
      vasculitis. Increased awareness is essential to secure a timely diagnosis and to
      promptly initiate treatment since our data emphasize a high mortality,
      particularly in those with cardiac involvement and significant accrued damage.

PMID- 27026727
TI  - Survey of Patient Insurance Status on Access to Specialty Foot and Ankle Care
      Under the Affordable Care Act.
AB  - BACKGROUND: The purpose of this study was to assess the effect of insurance type
      (Medicaid, Medicare, and private insurance) on access to foot and ankle surgeons
      for total ankle arthroplasty. METHODS: We called 240 foot and ankle surgeons who
      performed total ankle arthroplasty in 8 representative states (California,
      Massachusetts, Ohio, New York, Florida, Georgia, Texas, and North Carolina). The
      caller requested an appointment for a fictitious patient to be evaluated for a
      total ankle arthroplasty. Each office was called 3 times to assess the responses
      for Medicaid, Medicare, and BlueCross. From each call, we recorded appointment
      success or failure and any barriers to an appointment, such as need for a
      referral. RESULTS: Patients with Medicaid were less likely to receive an
      appointment compared to patients with Medicare (19.8% vs 92.0%, P < .0001) or
      BlueCross (19.8% vs 90.4%, P < .0001) and experienced more requests for referrals
      compared to patients with Medicare (41.9% vs 1.6%, P < .0001) or BlueCross (41.9%
      vs 4%, P < .0001). Waiting periods were longer for patients with Medicaid
      compared to those with Medicare (22.6 days vs 11.7 days, P = .004) or BlueCross
      (22.6 days vs 10.7 days, P = .001). Reimbursement rates did not correlate with
      appointment success rate or waiting period. CONCLUSION: Despite the passage of
      the PPACA, patients with Medicaid continue to have difficulty finding a surgeon
      who will provide care, increased need for a primary care referral, and longer
      waiting periods for appointments. LEVEL OF EVIDENCE: Level II, prognostic study.

PMID- 27026728
TI  - Oral Steroid Usage for Otitis Media with Effusion, Eustachian Tube Dysfunction,
      and Tympanic Membrane Retraction.
AB  - OBJECTIVES: Avoiding oral steroids for otitis media with effusion (OME) is
      endorsed as a performance measure by the National Quality Foundation, but data
      regarding current gaps and practice patterns are lacking. Our objectives were to
      evaluate oral steroid use for OME and the related diagnoses of eustachian tube
      dysfunction (ETD) and tympanic membrane retraction (TMR), to assess variations by
      visit setting, and to identify opportunities for measurable performance
      improvement. STUDY DESIGN: Cross-sectional analysis of a national database.
      SETTING: Ambulatory visits in the United States. SUBJECTS: Children and adults in
      the National Ambulatory Medical Care Survey and the National Hospital Ambulatory
      Medical Care Survey (2005-2010). METHODS: Data were coded for patient demographic
      information, potential confounders (eg, concurrent conditions managed by oral
      steroids), and diagnosis of OME, ETD, or TMR (OME/ETD/TMR). The latter 2
      diagnoses were included to meet minimum numbers for reliability of weighted
      estimates, but OME constituted the majority of cases. Multivariate regression was
      used to determine the variables associated with oral steroid use. RESULTS: Among
      590,772 observations representing 7,191,711,480 visits for OME/ETD/TMR, 3.2%
      resulted in a new prescription for oral steroid medication (2.3% for children,
      7.0% for adults). Adults were more likely to receive steroids (odds ratio = 3.50,
      P < .001) than those with other diagnoses, but a similar association was not
      found for children. Patients seen by an otolaryngologist or in the emergency
      department were less likely to receive steroids than those seen in other
      settings. CONCLUSIONS: OME/ETD/TMR is infrequently treated with oral steroids,
      particularly in children. Opportunities for performance improvement are limited.

PMID- 27026729
TI  - Management Strategies for Skull Base Inverted Papilloma.
AB  - OBJECTIVE: Inverted papilloma attached to the ventral skull base presents a
      surgical dilemma because surgical removal of the bony pedicle is critical to
      decrease risk of recurrence. The objective of this study is to evaluate the
      effectiveness of endoscopic management of skull base inverted papilloma. STUDY
      DESIGN: Case series with planned data collection. SETTING: Tertiary medical
      center. SUBJECTS: Patients with skull base inverted papilloma. METHODS: Over 7
      years, 49 patients with skull base inverted papilloma were referred for surgical
      resection. Demographics, operative technique, pathology, complications,
      recurrence, and postoperative follow-up were evaluated. RESULTS: Average age at
      presentation was 57 years. Twenty-six patients (53%) had prior attempts at
      resection elsewhere, and 5 had squamous cell carcinoma (SCCA) arising in an
      inverted papilloma. Six patients (12%) suffered major complications, including
      skull base osteomyelitis in 2 previously irradiated patients, cerebrospinal fluid
      leak with pneumocephalus (n = 1), meningitis (n = 1), invasive fungal sinusitis
      (n = 1), and cerebrovascular accident (n = 1). The mean disease-free interval was
      29 months (range, 10-78 months). One patient with SCCA recurred in the
      nasopharynx (overall 2% recurrence rate). He is disease-free 3 years following
      endoscopic nasopharyngectomy. Three patients with SCCA had endoscopic resection
      of the skull base, while 1 subject with inverted papilloma pedicled on the
      superior orbital roof had an osteoplastic flap in conjunction with a Draf III
      procedure. All others received endoscopic resection. CONCLUSIONS: Removal of the
      bony pedicle resulted in excellent local control of skull base inverted
      papillomas. Our experience demonstrates that disease eradication with limited
      morbidity is attainable with this approach.

PMID- 27026730
TI  - Effects of Memantine on Aminoglycoside-Induced Apoptosis of Spiral Ganglion Cells
      in Guinea Pigs.
AB  - OBJECTIVE: To explore whether memantine, an N-methyl-D-aspartate receptor
      antagonist, exerts a neuroprotective effect against apoptosis of spiral ganglion
      cells (SGCs) induced by gentamicin. STUDY DESIGN: An animal experiment. SETTING:
      Dong-A University College of Medicine, Busan, Korea. SUBJECTS AND METHODS:
      Gentamicin was injected into the left cochleae of guinea pigs to induce apoptosis
      of SGCs; the contralateral cochleae served as controls. Memantine was
      intraperitoneally injected 12 hours and 1 hour prior to gentamicin injection. At
      1 week after gentamicin and/or memantine injection, the cochleae were removed and
      stained with hematoxylin and eosin to evaluate morphologic changes and apoptosis.
      Western blotting was performed to measure FasL expression and the extent of
      caspase activation in SGCs. RESULTS: SGC numbers remained stable after memantine
      treatment. Western blotting showed that FasL expression and activation of
      caspases 3, 8, and 9 were reduced in SGCs after memantine treatment. CONCLUSION:
      Memantine attenuated the gentamicin-induced apoptosis of SGCs in guinea pigs.
      Moreover, memantine may affect Fas-FasL signaling in the receptor-mediated
      apoptotic pathway and caspase activation involved in the receptor-mediated and
      mitochondrial apoptotic pathways.

PMID- 27026731
TI  - Survival and Prognosis for Malignant Tumors of Odontogenic Origin.
AB  - OBJECTIVE: Determine survival and factors affecting survival for patients with
      malignant tumors of odontogenic origin. STUDY DESIGN: Retrospective analysis of
      the National Cancer Institute's SEER database (Surveillance, Epidemiology, and
      End Results). SETTING: Tertiary medical center. SUBJECTS AND METHODS: All cases
      of malignant tumors of odontogenic origin were extracted from the SEER database
      for the period of 1973 to 2011. Demographic, tumor-specific, and survival data
      were tabulated and Kaplan-Meier survival analysis conducted according to
      histopathologic results. Cox regression analysis stratified for histopathology
      was conducted to determine factors that influenced survival. RESULTS: A total of
      308 cases of malignant tumors with odontogenic origin were analyzed. Malignant
      ameloblastoma accounted for 59.7% of cases, followed by malignant odontogenic
      tumor (35.4%; including odontogenic carcinoma, odontogenic sarcoma, primary
      intraosseous carcinoma, and ameloblastic carcinoma) and ameloblastic fibrosarcoma
      (2.9%). The overall mean and median were 229 and 227 months, respectively, while
      the 5-year survival rate was 81% for the entire cohort. Malignant ameloblastoma
      exhibited the best mean survival (237 months), whereas malignant odontogenic
      tumor (139 months) and ameloblastic fibrosarcoma (42 months) had lower mean
      survival rates. Younger age, surgery with adjuvant radiation, and smaller tumor
      size were found to improve survival. CONCLUSIONS: Significantly different
      survival can be expected depending on individual tumor histopathology, tumor
      size, age at diagnosis, and treatment modality.

PMID- 27026732
TI  - Prevalence of Voice Disturbances in the Pediatric Craniofacial Patient
      Population.
AB  - OBJECTIVE: To report on the prevalence of voice disturbances in the pediatric
      craniofacial population and to prove that the pediatric Voice Handicap Index
      (pVHI) is a useful questionnaire for this unique population. STUDY DESIGN: Case
      series with chart review. SETTING: Tertiary care center. SUBJECTS: Pediatric
      patients seen by a pediatric otolaryngologist in a craniofacial clinic. METHODS:
      Consecutive patients (N = 366) seen by a single pediatric otolaryngologist in a
      craniofacial clinic from July 2011 to September 2012 were included. Any patient
      specifically referred for airway problems or voice difficulties completed a pVHI
      questionnaire. Patients each underwent an evaluation including flexible
      fiberoptic laryngoscopy and videostroboscopy. Voice disturbance was further
      characterized into dysphonia, hypernasality, or hyponasality. RESULTS: Of all the
      patients evaluated, 280 (77%) were specifically referred for airway problems or
      voice disturbance. Of those referred, 39 (10.7%) were found to have an organic
      vocal fold pathology causing dysphonia, as seen on the videostroboscopic
      examination; 53.7% of these lesions were attributable to potential iatrogenic
      causes. Hypernasality and hyponasality were seen in 116 (31.7%) and 78 (21.3%)
      patients, respectively. The pVHI was 3.95, 26.3, 11.34, and 10.53 for those with
      no voice disturbance, dysphonia, hypernasality, and hyponasality, respectively.
      CONCLUSION: Pediatric patients with craniofacial disorders have a higher
      prevalence of dysphonia than the general pediatric population. The majority of
      causes of dysphonia in these patients are possibly iatrogenic in origin. The pVHI
      serves as a useful questionnaire in this unique patient cohort to quantify the
      disability from not only dysphonia but also hypernasality and hyponasality.

PMID- 27026733
TI  - Sudden-Onset Sensorineural Hearing Loss after Immunization: A Case-Centered
      Analysis.
AB  - OBJECTIVE: Case reports of sudden sensorineural hearing loss (SSHL) following
      vaccines have led to concerns that vaccines may rarely cause hearing loss.
      Because of this concern, we analyzed for an association between SSHL and
      vaccinations. STUDY DESIGN: We used a case-centered method, equivalent to a case
      control design using immunization dates from all matched members of the
      population to calculate exposure to vaccines, rather than sampling. SETTING:
      Kaiser Permanente Northern California (KPNC), 2007 to 2013. SUBJECTS AND METHODS:
      We searched KPNC databases from 2007 to 2013 for all first-time diagnoses of
      SSHL. We used the date of any hearing- or ear-related visit in the 60 days prior
      to the first SSHL diagnosis as the onset date. Using only SSHL cases immunized in
      the prior 9 months, we compared the vaccine exposure in several risk intervals
      prior to onset with the exposure to the same vaccine during the same time period
      in all KPNC membership, matched to sex and age. RESULTS: During the study period,
      >20 million vaccines were administered at KPNC. In all risk intervals prior to
      onset of SSHL, we found no evidence of increased risk of immunization compared
      with matched controls. The odds ratios for vaccination 1 week prior to SSHL were
      0.965 (95% confidence interval, 0.61-1.50) for trivalent inactivated influenza
      vaccine (TIV); 0.842 (0.39-1.62) for tetanus, reduced diphtheria, and reduced
      acellular pertussis; and 0.454 (0.08-1.53) for zoster vaccine. CONCLUSION: A
      large-scale analysis applying a case-centered method did not detect any
      association between SSHL and previous receipt of TIV or other vaccines.

PMID- 27026734
TI  - Olfactory and Gustatory Functions after Anterior Palatoplasty in Patients with
      Primary Snoring.
AB  - OBJECTIVE: In this study, we investigated the chemical senses (namely,
      olfaction), the 4 basic tastes, and umami taste in patients who underwent
      anterior palatoplasty (AP) for primary snoring. STUDY DESIGN: Prospective
      clinical study. SETTING: Multicenter, tertiary care hospitals. SUBJECTS AND
      METHODS: The age range of the 28 participants was 22 to 47 years, and all had
      been diagnosed with primary snoring by polysomnography. Orthonasal and retronasal
      olfactory testing was performed using the respective "Sniffin' Sticks." Tests for
      the 4 basic tastes (sweet, sour, salty, and bitter) and umami were performed
      before and 6 months after AP. RESULTS: The changes between the preoperative and
      postoperative results for the 4 basic tastes, which were applied to the anterior
      tongue region, were not significant. Retronasal olfactory function improved
      significantly 6 months after AP (P = .007). After AP, umami scores for the soft
      palate but not those of the anterior and posterior tongue decreased significantly
      (P = .001). CONCLUSION: Patients scheduled for AP should be properly informed
      about potential postoperative taste and flavor changes. They should also be
      warned of a possible loss of appetite due to a postoperative decrease in the
      umami taste sensation of the soft palate.

PMID- 27026735
TI  - Survival Impact of Initial Therapy in Patients with T1-T2 Glottic Squamous Cell
      Carcinoma.
AB  - OBJECTIVE: Laryngeal cancer most commonly arises from the glottis. Comparable
      outcomes in survival have been shown in patients with early glottic squamous cell
      carcinoma treated with either surgery or radiotherapy. STUDY DESIGN AND SETTING:
      Administrative database study. SUBJECTS AND METHODS: The US National Cancer
      Institute's SEER database (Surveillance, Epidemiology, and End Results) was
      queried for cases of early glottic cancer (T1-T2N0M0, 1988-2012). We identified
      13,312 qualifying cases. Patient demographics, therapeutic measures, and survival
      outcomes were examined with appropriate univariate and multivariate analyses.
      RESULTS: Early glottic cancer has a mean age at diagnosis of 64.8 +/- 11.6 years
      and a male:female ratio of 6.9:1. The most common treatment modality was
      radiotherapy alone (51.6%), followed by combination therapy with surgery first
      (31.5%). Overall, the 5-year disease-specific survival (DSS) rate was 88.4%. When
      stratified by treatment modality and stage, 5-year DSS for T1 tumors was 93.2%
      with surgery alone and 89.0% with radiation alone (P < .0001). With combination
      therapy, the 5-year DSS was 91.3% for surgery first and 84.9% for radiation first
      (P = .0239). In T2 tumors, 5-year DSS was improved with single-modality therapy
      versus multimodality therapy (81.1% vs 76.4; P = .0255). CONCLUSION: In T1
      disease, surgery alone shows improved 5-year DSS versus radiation alone, but this
      difference was not observed in T2 tumors. Additionally, surgery, rather than
      radiation, shows improved 5-year DSS when implemented as a first-line therapy.
      Combination therapy does not show improved 5-year DSS for early glottic cancer.

PMID- 27026736
TI  - Laryngeal Preservation in Glottic Cancer: A Comparison of Hospital Charges and
      Morbidity among Treatment Options.
AB  - OBJECTIVE: When total laryngectomy is not required, organ preservation surgery or
      radiotherapy is considered the standard of care for primary glottic cancer. These
      accepted treatment options are available for early and advanced glottic cancers
      due to equivalent locoregional control and survival rates. However, in today's
      climate of accountable care, the financial burden of treatment choices continues
      to increase in significance. We therefore compared hospital charges and treatment
      related morbidity between organ-preserving surgery and radiation with or without
      chemotherapy-herein, (chemo)radiation-in the primary treatment of glottic cancer.
      STUDY DESIGN: Nationwide Inpatient Sample Database was analyzed to assess
      clinical and financial information. SETTING: Population-based analysis. SUBJECTS:
      Patients (N = 5499) with primary glottic cancer undergoing treatment with
      laryngeal preservation strategies. METHODS: Patients were subdivided by ICD-9
      codes into 3 treatment groups: endoscopic resection, open partial laryngectomy,
      and (chemo)radiation. Treatment-related outcomes, charges, and length of
      hospitalization were analyzed among treatment groups. RESULTS: When adjusting for
      sex, age, race, comorbidity, and primary payer, (chemo)radiotherapy was
      associated with increased direct charges (P < .001; coefficient, $23,658.99; 95%
      confidence interval [95% CI]: $10,227.15-$37,090.84) and length of
      hospitalization (P < .001; hazard ratio, 0.593; 95% CI: 0.502-0.702) when
      compared with endoscopic surgery. As compared with open surgery, endoscopic
      surgery was associated with reduced hospital charges (P = .012; coefficient,
      $11,967.01; 95% CI: $2,784.17-$21,249.85) and duration of hospitalization (P <
      .001; hazard ratio, 0.749; 95% CI: 0.641-0.876). CONCLUSIONS: This analysis
      suggests that increased utilization of endoscopic surgery in patients with
      primary glottic cancer not requiring total laryngectomy may lead to reduced
      financial burden and duration of hospitalization when compared with open surgery
      or (chemo)radiation therapy.

PMID- 27026737
TI  - Peritonsillar Abscess: Complication of Acute Tonsillitis or Weber's Glands
      Infection?
AB  - OBJECTIVE: To review the literature concerning the 2 primary hypotheses put forth
      to explain the pathogenesis of peritonsillar abscess: "the acute tonsillitis
      hypothesis" (peritonsillar abscess is a complication of acute tonsillitis) and
      "the Weber gland hypothesis" (peritonsillar abscess is an infection of Weber's
      glands). DATA SOURCES: PubMed, EMBASE. REVIEW METHODS: Data supporting or
      negating one hypothesis or the other were elicited from the literature.
      CONCLUSIONS: Several findings support the acute tonsillitis hypothesis. First,
      the 2 main pathogens in peritonsillar abscess have been recovered from pus
      aspirates and bilateral tonsillar tissues with high concordance rates, suggesting
      that both tonsils are infected in patients with peritonsillar abscess. Second,
      studies report signs of acute tonsillitis in the days prior to and at the time of
      peritonsillar abscess. Third, antibiotic treatment reduces the risk of abscess
      development in patients with acute tonsillitis. However, some findings suggest
      involvement of the Weber's glands in peritonsillar abscess pathogenesis. First,
      high amylase levels have been found in peritonsillar pus. Second, the majority of
      peritonsillar abscesses are located at the superior tonsillar pole in proximity
      of the Weber's glands. We propose a unified hypothesis whereby bacteria initially
      infect the tonsillar mucosa and spread via the salivary duct system to the
      peritonsillar space, where an abscess is formed. IMPLICATIONS FOR PRACTICE: Our
      findings support the rationale for antibiotic treatment of patients with severe
      acute tonsillitis to reduce the risk of abscess development. Improved
      understanding of peritonsillar abscess pathogenesis is important for the
      development of efficient prevention strategies.

PMID- 27026738
TI  - Human Papillomavirus Vaccination Counseling in Pediatric Training: Are We
      Discussing Otolaryngology-Related Manifestations?
AB  - OBJECTIVE: Demonstrate the need for increased education regarding otolaryngology
      related manifestations of human papillomavirus (HPV). Highlight a need to
      incorporate otolaryngology-related manifestations of HPV in vaccine counseling.
      STUDY DESIGN: Survey. SETTING: Tertiary care academic children's hospital.
      SUBJECTS: Pediatric residents, fellows, and staff. METHODS: An online survey was
      made available regarding HPV education and vaccination. RESULTS: Participants (N
      = 348) initiated the survey representing 28.4%, 25.6%, and 19.0% postgraduate
      year 1, 2, and 3 residents, respectively, as well as 17.5% chief
      residents/fellows and 9.5% attendings. Participants rated their prior education
      as none or fair regarding recurrent respiratory papillomatosis (63.8%) and
      oropharyngeal squamous cell carcinoma (68.3%). In contrast, 60.6% and 70.9% rated
      their education on genital warts and cervical cancer correspondingly as good or
      excellent. When asked what was routinely discussed during HPV vaccine counseling,
      63.3% reported "never" discussing recurrent respiratory papillomatosis and 52.9%
      "never" discussing oropharyngeal squamous cell carcinoma. A range from 92.7% to
      95.5% responded that there was a need for increased education regarding HPV and
      its role in recurrent respiratory papillomatosis and oropharyngeal squamous cell
      carcinoma. CONCLUSIONS: Increased education about HPV and its otolaryngology
      related manifestations should be undertaken to increase provider, patient, and
      parent awareness of recurrent respiratory papillomatosis and oropharyngeal
      squamous cell carcinoma. We propose that discussing the risks of otolaryngology
      related disease be routinely included in HPV vaccination counseling.

PMID- 27026739
TI  - The Pursuit of Otolaryngology Subspecialty Fellowships.
AB  - OBJECTIVES: To examine otolaryngology resident interest in subspecialty
      fellowship training and factors affecting interest over time and over the course
      of residency training STUDY DESIGN: Cross-sectional study of anonymous online
      survey data. SETTING: Residents and fellows registered as members-in-training
      through the American Academy of Otolaryngology-Head and Neck Surgery. SUBJECTS
      AND METHODS: Data regarding fellowship interest and influencing factors,
      including demographics, were extracted from the Section for Residents and Fellows
      Annual Survey response database from 2008 to 2014. RESULTS: Over 6 years, there
      were 2422 resident and fellow responses to the survey. Senior residents showed a
      statistically significant decrease in fellowship interest compared with junior
      residents, with 79% of those in postgraduate year (PGY) 1, 73% in PGY-2 and PGY
      3, and 64% in PGY-4 and PGY-5 planning to pursue subspecialty training (P <
      .0001). Educational debt, age, and intended practice setting significantly
      predicted interest in fellowship training. Sex was not predictive. The most
      important factors cited by residents in choosing a subspecialty were consistently
      type of surgical cases and nature of clinical problems. CONCLUSIONS: In this
      study, interest in pursuing fellowship training decreased with increased
      residency training. This decision is multifactorial in nature and also influenced
      by age, educational debt, and intended practice setting.

PMID- 27026740
TI  - Double Burden of Undernutrition and Obesity in Palestinian Schoolchildren: A
      Cross-Sectional Study.
AB  - BACKGROUND: The coexistence of underweight and overweight (double burden) remains
      a major problem in many developing countries. Little is known about the factors
      associated with the double burden of malnutrition in Palestinian children.
      OBJECTIVE: To assess factors associated with undernutrition and overnutrition in
      1500 schoolchildren aged 5 to 16 years, in the West Bank. METHODS: We surveyed a
      sample of 22 schools run by the United Nations Relief and Works Agency for
      Palestine Refugees in the Near East (UNRWA) and the Palestinian government.
      Binary logistic regression was used to examine the factors associated with
      malnutrition. The hunger index, a composite score from 8 questions, was used to
      measure food insecurity. RESULTS: In the 1484 children enrolled in UNRWA and
      government schools in the West Bank, the prevalence of stunting was 7% and
      underweight 3%. Around 12% of students were overweight and 6% obese. The hunger
      index was negatively associated with height for age. Factors associated with
      being underweight were male sex, mother being unemployed, and households not
      having enough food to eat for at least 2 days in the previous month. Factors
      associated with obesity were older age and time spent watching television. When
      overweight and obesity were combined in the analysis, they were inversely
      associated with increasing number of days spent playing sports. CONCLUSION: Our
      results show that the important nutritional risks for school-age children in the
      West Bank would seem to be the simultaneous occurrence of undernutrition and
      obesity. The study highlights the need to balance obesity management and
      prevention with interventions to tackle undernutrition.

PMID- 27026742
TI  - STUDY OF RADIATION EXPOSURE DUE TO RADON, THORON AND PROGENY IN THE INDOOR
      ENVIRONMENT OF YAMUNA AND TONS VALLEYS OF GARHWAL HIMALAYA.
AB  - Long-term measurements of indoor radon, thoron and their progeny concentrations
      have been carried out in dwellings of Yamuna and Tons Valleys of Uttarkashi,
      Garhwal Himalaya to investigate the health risk associated with inhalation of
      radon, thoron and progeny. The experimentally determined values of radon, thoron
      and progeny concentrations were used to estimate the annual inhalation doses and
      annual effective doses. The annual inhalation dose has been found to vary from
      0.8 to 3.9 mSv y-1 with an average of 1.8 mSv y-1 The annual effective dose from
      the exposure to radon and its progeny in the study area has been found to vary
      from 0.1 to 2.4 mSv with an average of 1.2+/-0.6 mSv. Similarly, the annual
      effective dose due to thoron and its progeny has been found to vary from 0.2 to
      1.5 mSv with an average of 0.6+/-0.4. The measurement techniques and results
      obtained are discussed in detail.

PMID- 27026743
TI  - STUDY ON RADON CONCENTRATION AT THE WORK PLACES OF MYSURU, BENGALURU AND KOLAR
      DISTRICTS OF KARNATAKA STATE, SOUTH INDIA.
AB  - Concentrations of radon, thoron and their progeny inside the working place depend
      on the activity of radionuclides in the soil, building materials, atmospheric
      conditions, construction of the building, type of work and ventilation condition.
      Radon is a radioactive noble gas, and it is emanated from 226Ra present in earth
      crest and building material. Based on the type of work, construction of the
      building and ventilation condition, concentrations of radon, thoron and their
      progeny have been measured in 60 workplaces at 10 locations of Mysuru, Bengaluru
      and Kolar districts of Karnataka state using Solid-State Nuclear Track Detector
      technique. From the study, variations of radon, thoron and their progeny have
      been observed with the nature of work.

PMID- 27026744
TI  - NATURAL RADIOACTIVITY LEVEL AND ELEMENTAL COMPOSITION OF SOIL SAMPLES FROM A HIGH
      BACKGROUND RADIATION AREA ON EASTERN COAST OF INDIA (ODISHA).
AB  - A comprehensive study was carried out to determine the radioactivity
      concentration of soil samples from different sites of a high background radiation
      area in the eastern coast of India, Odisha state. The dose rate measured in situ
      varied from 0.25 to 1.2 uSv h-1 The gamma spectrometry measurements indicated Th
      series elements as the main contributors to the enhanced level of radiation and
      allowed the authors to find the mean level of the activity concentration (+/-SD)
      for 226Ra, 228Th and 40K as 130+/-97, 1110+/-890 and 360+/-140 Bq kg-1,
      respectively. Human exposure from radionuclides occurring outdoor was estimated
      based on the effective dose rate, which ranged from 0.14+/-0.02 to 2.15+/-0.26
      mSv and was higher than the UNSCEAR annual worldwide average value 0.07 mSv.
      Additionally, X-ray fluorescence analysis provided information about the content
      of major elements in samples and indicated the significant amount of Ti (7.4+/
      4.9 %) in soils.

PMID- 27026745
TI  - INFLUENCE OF DIFFERENT TYPES OF PHANTOMS ON THE CALIBRATION OF DOSEMETERS FOR EYE
      LENS DOSIMETRY.
AB  - Both a cylinder and a slab phantom have been recommended to be used as
      calibration phantoms for eye lens dosimetry in the International Atomic Energy
      Agency TECDOC. This study describes investigations on the influence of the type
      of phantom on the calibration of dosemeters. In order to fulfil the purpose,
      backscatter radiation from practically used water-filled phantoms was evaluated
      by calculations and experiments. For photons, the calculations showed that the
      cylinder phantom had 10 % lower backscattered effect at maximum than a slab
      phantom, and simulated well the backscattered effect of the human head or neck to
      within +/-10 %. The irradiation results of non-filtered optically stimulated
      luminescence and radio-photoluminescence glass dosemeters indicated that the
      differences of the calibration factors between the two types of phantoms were up
      to 20 and 10 %, respectively, reflecting the response to backscattered photons.
      For electrons, no difference was found between the two types of phantoms. 

PMID- 27026746
TI  - STUDY OF RADON, THORON EXHALATION AND NATURAL RADIOACTIVITY IN COAL AND FLY ASH
      SAMPLES OF KOTA SUPER THERMAL POWER PLANT, RAJASTHAN, INDIA.
AB  - Electricity generation in India is largely dependent on coal-based thermal power
      plants, and increasing demand of energy raised the coal consumption in the power
      plants. In recent years, study of natural radioactivity content and radon/thoron
      exhalation from combustion of coal and its by-products has given considerable
      attention as they have been recognised as one of the important technically
      enhanced naturally occurring radioactive materials. In the present study, radon,
      thoron exhalation rate and the radioactivity concentration of radionuclides in
      coal and fly ash samples collected from Kota Super Thermal Power Plant,
      Rajasthan, India have been measured and compared with data of natural soil
      samples. The results have been analysed and discussed.

PMID- 27026747
TI  - Probability of diagnosing long QT syndrome in children and adolescents according
      to the criteria of the HRS/EHRA/APHRS expert consensus statement.
AB  - AIMS: The present study aimed to determine the probability of diagnosing long QT
      syndrome (LQTS) in children and adolescents based on the HRS/EHRA/APHRS criteria
      for LQTS. We used data of a school-based electrocardiographic screening programme
      in Japan. METHODS AND RESULTS: The total numbers of subjects who participated in
      the screening programme between 2008 and 2013 in Kagoshima, Japan, were 33 051
      first- and 34 751 seventh-grade students, aged 6 and 12 years, respectively. The
      screening process consisted of three steps of examination: the first screening,
      and the second and third examinations. Among the total subjects, 32 982 first
      graders (99.8% of the total) and 34 572 seventh graders (99.5% of the total)
      participated in the first screening. After the first, second, and third screening
      or examinations, the programme determined 10 first and 32 seventh graders as
      having a high probability of LQTS according to the HRS/EHRA/APHRS criteria for
      LQTS. The probability of diagnosing LQTS by the screening programme was 1:3298
      (0.30/1000) and 1:1080 (0.93/1000) in first and seventh graders, respectively.
      During the study periods, three subjects of 7th graders were already diagnosed as
      having LQTS at the first grade. Therefore, the overall probability of diagnosing
      LQTS was 1:3298 (95% confidence interval, 1:2036 to 1:8673) and 1:988 (95%
      confidence interval, 1:742 to 1:1477) in first and seventh graders, respectively.
      CONCLUSION: This study shows important data on the probability of diagnosing LQTS
      as ~1:3300 in subjects aged 6 years and 1:1000 in those aged 12 years based on
      the HRS/EHRA/APHRS criteria.

PMID- 27026748
TI  - Replacing statins with PCSK9-inhibitors and delaying treatment until 18 years of
      age in patients with familial hypercholesterolaemia is not a good idea.

PMID- 27026749
TI  - Lower might be better - It matters how you get there, and in whom.

PMID- 27026750
TI  - Contemporary outcomes after surgical aortic valve replacement with bioprostheses
      and allografts: a systematic review and meta-analysis.
AB  - Many observational studies have reported outcomes after surgical aortic valve
      replacement (AVR), but there are no recent systematic reviews and meta-analyses
      including all available bioprostheses and allografts. The objective of this study
      is to provide a comprehensive and up-to-date overview of the outcomes after AVR
      with bioprostheses and allografts reported in the last 15 years. We conducted a
      systematic literature review (PROSPERO register: CRD42015017041) of studies
      published between 2000-15. Inclusion criteria were observational studies or
      randomized controlled trials reporting on outcomes of AVR with bioprostheses
      (stented or stentless) or allografts, with or without coronary artery bypass
      grafting (CABG) or valve repair procedure, with study population size n >= 30 and
      mean follow-up length >=5 years. Fifty-four bioprosthesis studies and 14
      allograft studies were included, encompassing 55 712 and 3872 patients and 349
      840 and 32 419 patient-years, respectively. We pooled early mortality risk and
      linearized occurrence rates of valve-related events, reintervention and late
      mortality in a random-effects model. Sensitivity, meta-regression and subgroup
      analyses were performed to investigate the influence of outliers on the pooled
      estimates and to explore sources of heterogeneity. Funnel plots were used to
      investigate publication bias. Pooled early mortality risks for bioprostheses and
      allografts were 4.99% (95% confidence interval [CI], 4.44-5.62) and 5.03% (95%
      CI, 3.61-7.01), respectively. The late mortality rate was 5.70%/patient-year (95%
      CI, 4.99-5.62) for bioprostheses and 1.68%/patient-year (95% CI, 1.23-2.28) for
      allografts. Pooled reintervention rates for bioprostheses and allografts were
      0.75%/patient-year (95% CI, 0.61-0.91) and 1.87%/patient-year (95% CI, 1.52
      2.31), respectively. There was substantial heterogeneity in most outcomes. Meta
      regression analyses identified covariates that could explain the heterogeneity:
      implantation period, valve type, patient age, gender, pre-intervention New York
      Heart Association class III/IV, concomitant CABG, study design and follow-up
      length. There is possible publication bias in all outcomes. This comprehensive
      systematic review and meta-analysis provides an overview of the outcomes after
      AVR with bioprostheses and allografts reported during the last 15 years. The
      results of this study can support patients and doctors in the prosthetic valve
      choice and can be used in microsimulation models to predict patient outcomes and
      estimate the cost-effectiveness of AVR with bioprostheses or allografts compared
      with current and future heart valve prostheses.

PMID- 27026751
TI  - Increasing aphasia treatment intensity in an acute inpatient rehabilitation
      program: A feasibility study.
AB  - BACKGROUND: Intensity of therapy is a critical factor influencing outcomes in
      aphasia. However, there are many barriers to increasing treatment intensity for
      those with acute/subacute aphasia including the demands of the inpatient medical
      facilities and the endurance of the participants. Nevertheless, with some
      modifications to its original procedures, evidence suggests that Constraint
      Induced Language Therapy (CILT) may yield positive outcomes when given in the
      early stages of recovery. AIMS: To investigate the feasibility of increasing the
      amount of therapy provided to individuals with aphasia on an inpatient
      rehabilitation unit by adding CILT at a modified intensity, and to assess whether
      those receiving two weeks of the additional CILT show more improvement than
      control participants who did not receive the additional treatment. METHODS AND
      PROCEDURES: A case-series single-subject design study was conducted. All
      participants received usual care of approximately an hour of speech and language
      treatment, five to six days a week. Participants in the experimental condition
      received an additional hour-long CILT session, five days per week, for two weeks.
      Trained, untrained, and generalization probes comprising naming of pictured items
      and oral reading of sentences were taken at baseline, during treatment, and at
      post-treatment. All participants were probed equally. Probe performance was
      scored and effect sizes were calculated and compared. Performance gains from pre-
      to post-treatment on subtests of the Boston Diagnostic Aphasia Examination were
      also compared. OUTCOMES AND RESULTS: Thirteen individuals with aphasia onset
      ranging from 7 to 68 days were recruited, with 6 allocated to the experimental
      Usual Care + CILT condition and 7 allocated to the control Usual Care condition.
      Increasing the amount of speech and language therapy by adding an hour of daily
      CILT was feasible. Individual performance varied within and across conditions
      with large gains noted in some, but not all participants. As a group, there was a
      small to medium effect size of the Usual Care + CILT condition over Usual Care
      alone for trained and untrained oral reading probes and untrained naming probes.
      CONCLUSIONS: It is feasible to increase the amount of treatment provided to
      participants with aphasia on an acute inpatient rehabilitation unit. Preliminary
      results suggest that there may be better outcomes for those who receive more
      treatment. Further research using larger numbers of homogeneous participants and
      controlling for content of therapy as well as amount of therapy is warranted.

PMID- 27026752
TI  - Reliability, Validity, and Variability of the Subjective Well-Being Questions in
      the 2010 American Time Use Survey.
AB  - Part of a wider range of investigations to produce generally acceptable standards
      for measuring affective well-being, time diary surveys have tested several
      approaches to measuring subjective well-being during diary days. As an
      alternative to the standard approach of asking a single question about each
      activity reported in time diary surveys, the 2010 module of the American Time Use
      Survey asked six emotion questions about three activities. The perception
      questions captured how happy, meaningful, sad, tired, stressed, or in pain
      respondents felt on a 7-point scale. To evaluate this approach, our research
      examined the reliability and validity of the six emotion questions, and assessed
      their variability across activities. Using principal component analysis, we
      assessed the associations among items and obtained two activity-level components
      with Cronbach's alphas of 0.68 and 0.59 and two respondent-level components with
      Cronbach's alphas of 0.74 and 0.65. To test validity, we regressed self-rated
      health on the underlying components and socio-demographic controls. Both of the
      respondent level components were significantly associated with better health
      (odds ratio 1.81, 1.27). Using each of the perceptions individually, we found
      that happiness, meaningfulness, and lack of fatigue, stress, and pain were
      related to better health, but none as strongly as the first component. Finally,
      we examined the coefficients of variation to assess the variability in the well
      being measures across activities. Measurement implications and limitations of
      this study are discussed.

PMID- 27026754
TI  - The Journey of Publication Process of The Eurasian Journal of Medicine: From a
      Local University Journal Promoting to Emerging Sources Citation Indexed (ESCI).

PMID- 27026753
TI  - A Twin Study of Objective and Subjective Pubertal Timing and Peer Influence on
      Risk-Taking.
AB  - The current study used a behavioral genetic design to test whether three measures
      of pubertal timing moderated peer influence on risk-taking in a sample of 248
      female adolescent twin pairs (Mage =16.0, SD=1.5) from the National Longitudinal
      Study of Adolescent Health. Peer influence was operationalized as the quasi
      causal association between girls' self-reported risk-taking and the risk-taking
      reported by their friends. Girls with earlier ages at menarche and who perceived
      themselves as more developed than peers were more susceptible to peer influence
      on risk-taking. However, age-standardized ratings of body changes did not
      moderate peer influence. This study highlights distinctions between multiple
      measures of pubertal timing, using an innovative synthesis of genetically
      informative data and peer nomination data.

PMID- 27026755
TI  - The Frequency of Some Thrombophilic Mutations in Eastern Turkey.
AB  - OBJECTIVE: Factor V / Factor II / Methylenetetrahydrofolate reductase, gene
      polymorphisms are closely associated with thrombophilia. Regional frequencies of
      these mutations may show a characteristic state. The aim of our study was to
      evaluate the frequency of commonly seen Factor V / Factor II /
      Methylenetetrahydrofolate reductase gene polymorphisms in Eastern Turkey.
      MATERIALS AND METHODS: In 433 patients sent to the laboratory with the suspicion
      of thrombophilia, using whole blood samples, an automated Nucleic Acid Test was
      used for mutation determinations in Verigene System. The kit module was designed
      to detect the Factor V G1691A / Factor II G20210A / Methylenetetrahydrofolate
      reductase gene C677T single nucleotide polymorphisms. RESULTS: In 433 patients,
      8.7% for Factor V G1691A polymorphisms were heterozygous genotype, 3.9% for
      Factor II G20210A polymorphisms were heterozygous genotype, and 43.9% for
      methylenetetrahydrofolate reductase 677C>T polymorphisms were heterozygous
      genotype and 3.0% homozygous mutation genotype. CONCLUSION: Detection of these
      commonly seen Factor V / Factor II / Methylenetetrahydrofolate reductase single
      nucleotide polymorphisms can help to identify patients in high risk group and to
      evaluate the interaction of genetic and acquired risk factors. Our findings
      suggest that commonly seen thrombophilic allele mutation frequency in our region
      is the same as the data reported in the literature.

PMID- 27026756
TI  - General Characteristics of Child Sexual Offenders in Hatay, Turkey.
AB  - OBJECTIVE: Child sexual offenders are a poorly studied and relatively neglected
      population in our country. This study aims to evaluate the relationship between
      criminal behavior and socio-demographic characteristics of a series of child
      sexual offenders. MATERIALS AND METHODS: The records of social worker interviews
      with 48 child sexual offenders between 2009 and 2013 were used. The reports
      issued by social workers regarding child sexual offenders were retrospectively
      examined, since these reports were relatively the most thorough documents
      including offenders' personal and familial characteristics, and criminal event
      information. Cases were investigated in terms of socio-demographic and
      psychosocial characteristics. RESULTS: There were 48 children interviewed based
      on an alleged sexual crime, during four-year of study period. All of the cases
      were male and their ages ranged between 12 and 17 years. Of these, 50% were
      students at any grade of school. Five cases were living in social service
      facilities. Only two cases involved incest. Of all, three offenders were accused
      of repeated sexual crimes. Type of sexual assault was anal penetration in 20
      (41.7%) cases. Of all cases, 19 were cigarette smoker, while 4 were drug abusers.
      The families of 12 (25%) cases suffered from low socio-economic status, while 23
      (47.9%) offenders were members of broken families. According to social worker
      reports, 47 cases had criminal responsibility based on their psychosocial
      development. Out of all cases, 7 children were suspected of suffering from
      impulse control disorder and one was suspected to be mentally retarded. Twelve
      cases were reported to need consulting and social protective services.
      CONCLUSION: The rate of offenders with interrupted education was considerably
      high. Interestingly the number of male victims and the frequency of cases
      involving anal penetration were high. Obtained results suggest that male children
      of broken and scattered families, and particularly those lacking father's
      supervision were more likely to commit a sexual crime.

PMID- 27026757
TI  - CYP19A1 Genetic Polymorphisms rs4646 and Osteoporosis in Patients Treated with
      Aromatase Inhibitor-Based Adjuvant Therapy.
AB  - OBJECTIVE: Third-generation aromatase inhibitors (AI) are potent suppressors of
      aromatase activity. The aim of this study was to measure the incidence of adverse
      effects in breast cancer patients treated with AI-based adjuvant therapy and the
      relationship with the CYP19A1 genotypes. MATERIALS AND METHODS: Forty-five
      postmenopausal breast cancer patients (46-85 yrs) in AI adjuvant treatment were
      genotyped for the rs4646 polymorphisms of CYP19A1 gene and three variations were
      identified. Toxicities were registered at each follow-up medical examination, and
      classified in accord with the Common Terminology Criteria for Adverse Events.
      RESULTS: Twenty-four (53.3%) patients presented the GG genotype; 19 (42.2%) the
      GT, and 2 (4.4%) the TT. The AI treatment was Anastrazole for 35 patients (77.8%)
      and Letrozole for the others (n=10; 22.2%). Osteoporosis was significantly
      associated with the GG genotype (p=0.001). Treatment discontinuation (TD) was
      observed in 6 cases (13.3%). The only parameter able to predict TD was the
      appearance of severe arthralgia/myalgia (Odds Ratio, OR=23.75; p=0.009), when
      adjusted for age and AI treatment. CONCLUSION: Our results suggest that CYP19A1
      polymorphic variants may influence susceptibility to develop AI-related side
      effects. Further prospective studies are needed to confirm the role of the
      aromatase gene (CYP19A1) polymorphisms in predicting adverse effects to AI-based
      therapy.

PMID- 27026758
TI  - The Reliability of Turkish "Basic Life Support" and "Cardiac Massage" Videos
      Uploaded to Websites.
AB  - OBJECTIVE: In this study, the reliability of Turkish cardiac massage and Basic
      Life Support (BLS) videos, which have already been downloaded from three website
      such as YouTube, Google, Yahoo following the publication of 2010 cardiopulmonary
      resuscitation (CPR) guideline and their suitability to the same guideline were
      researched. MATERIALS AND METHODS: The videos uploaded to the three web-site to
      search videos on internet were queried by using the keywords "cardiac massage"
      and "basic life support". Videos that had been uploaded between January 2011 and
      July 2014 were analyzed and scored by two experienced emergency specialists.
      RESULTS: A total of 1126 videos were obtained. 1029 of the videos (91.4%) were
      excluded by researchers. 97 videos were detected to accord with study criteria.
      Despite most of the videos were found on Google website by keywords, the enormous
      part of videos proper to criteria were sourced from YouTube website (n=65,
      67.0%). One fourth of the videos (24.7%) were observed to not be suitable for
      2010 CPR guideline. AED usage was mentioned slightly in the videos (14.4%).
      Median score of the videos is 5 (IQR: 4-6). The rate and scores of the videos
      uploaded by official institution or association were significantly higher than
      others (p=0.007 and 0.006, respectively). Moreover, scores of the videos
      compatible with guidelines uploaded by official institution or association and
      medical personal were also found higher (p=0.001). CONCLUSION: Eventually, all
      the data obtained in this study support that Turkish videos were not reliable on
      the subject of BLS and cardiac massage. It is promising that videos with high
      follow-up rates also have been scored higher.

PMID- 27026759
TI  - Characteristics of Patients Who Admitted to the Emergency Department Because of
      Burns Due to Dens Liquids Such as Hot Milk/Oil.
AB  - OBJECTIVE: Burn is the tissue damage on body caused due to various reasons.
      Although all burns caused by hot liquids are investigated as scalding burns,
      dense liquid burns (DLB) caused by such as milk and oil are different from other
      burns. The aim of this study was to report the properties of DLB. MATERIALS AND
      METHODS: Patients admitted to the Emergency Service of Ataturk University
      Hospital, with DLB from June 2003 to December 2008, were examined
      retrospectively. RESULTS: During the study, 28 DLB patients were admitted to the
      emergency service. The most common admission were found in autumn 28.6% (n=8),
      and in May and June, 17.9% (n=5). The frequency of burns on the right upper
      extremity was seen in 50% (n=14) of the patients. The burn degree of all patients
      was determined as 2(nd) degree. Seventy-five percent (n=21) of the patients were
      discharged, 14.3% (n=4) were hospitalized. None of the patients died. CONCLUSION:
      Dense liquid burns is a burn type that is commonly seen in women, absolutely
      causing 2(nd) degree burns, frequently reported in upper extremity and head/neck
      regions, and in contrast to other studies, in our region it is completely seen in
      patients living in city centre.

PMID- 27026761
TI  - The Role of Choledochoscopy in Hepatopancreatobiliary Diseases.
AB  - OBJECTIVE: Advances in choledochoscopy technology lead to an improvement in the
      diagnosis and treatment of hepatopancreatobiliary diseases. The aim of this study
      is to reveal the role of choledochoscopy in hepatopancreatobiliary pathologies.
      MATERIALS AND METHODS: Choledochoscopy was used under general anesthesia in
      operation rooms. Flexible choledochoscope inserted via a vertical choledochotomy
      line, which was closed by primary closure, T-tube application, or
      choledochoduodenal anastomosis. Olympus CHF T 20 flexible choledochoscope and
      related endoscopic instruments were used for the procedures. The records were
      evaluated retrospectively. RESULTS: This study presents the findings of 235
      intraoperative choledochoscopy procedures. The most common indications were
      suspected common bile duct stone in 96 patients (40.9%), serum cholestatic enzyme
      increase without jaundice in 52 (22.1%), obstructive jaundice and/or serum
      bilirubin increase in 46 (19.6%), and presence of dilated choledoch in 42
      (17.9%). Additional endoscopic diagnostic and/or therapeutic procedures were
      performed 156 times in 125 patients (53.2%), and endoscopic biliary stone removal
      was the most used procedure (87 patients, 37.0%). The mean choledochoscopy
      duration was 8.5 minutes (range: 5-25 minutes). Choledochoscopy confirmed
      preliminary diagnosis in 117 patients (49.8%), while different data were elicited
      in 68 (28.9%), and normal findings were found in 50 (21.3%). In this series, no
      choledochoscopy-related mortality was seen, and some complications occurred in 4
      patients (1.7%). CONCLUSION: Intraoperative flexible choledochoscopy is a proper
      technique in the diagnosis and treatment of hepatopancreatobiliary disorders.

PMID- 27026760
TI  - An Evaluation of Surgical Prophylaxis Procedures in Turkey: A Multi-Center Point
      Prevalence Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate compliance with guidelines
      in surgical prophylaxis (SP) procedures in Turkey. MATERIALS AND METHODS: A point
      prevalence study involving 4 university, 5 education and research and 7 public
      hospitals was performed assessing compliance with guidelines for antibiotic use
      in SP. Compliance was based on the "Clinical Practice Guidelines for
      Antimicrobial Surgery (CPGAS) 2013" guideline. RESULTS: Sixteen centers were
      included in the study, with 166 operations performed at these being evaluated.
      Parenteral antibiotic for SP was applied in 161 (96.9%) of these. Type of
      antibiotic was inappropriate in 66 (40.9%) cases and duration of use in 47
      (29.1%). The main antibiotics used inappropriately in SP were ceftriaxone,
      glycopeptides and aminoglycosides. No significant difference was observed between
      secondary and tertiary hospitals in terms of inappropriate selection. Duration of
      prophylaxis was also incompatible with guideline recommendations in approximately
      half of surgical procedures performed in both secondary and tertiary hospitals,
      however statistical significance was observed between institutions in favor of
      tertiary hospitals. CONCLUSION: Antibiotics are to a considerable extent used in
      a manner incompatible with guidelines even in tertiary hospitals in Turkey. It
      must not be forgotten that several pre-, intra- and postoperative factors can be
      involved in the development of surgical site infections (SSI), and antibiotics
      are not the only option available for preventing these. A significant improvement
      can be achieved in prophylaxis with close observation, educational activities,
      collaboration with the surgical team and increasing compliance with guidelines.
      All health institutions must establish and apply their own SP consensus
      accompanied by the guidelines in order to achieve success in SP.

PMID- 27026763
TI  - A Study on the Age-Related Changes in Hepatitis B and C Virus Serology.
AB  - OBJECTIVE: There are a limited number of studies on the seroprevalence of
      Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection in Turkey. This
      study aimed to compare HBV and HCV seroprevalence rates before and after the
      implementation of national hepatitis B vaccination program (NHPVP) and to explore
      age-related changes in the seroprevalences. MATERIALS AND METHODS: Results of
      Hepatitis B surface antigen (HBsAg), Hepatitis B virus surface antibody (antiHBs)
      and anti-HCV tests performed during 2009 and 2010 in a state hospital laboratory
      were reviewed retrospectively. As NHPVP was started in 1998, 12 years of age and
      younger children were considered post- NHPVP period subjects. RESULTS: A total of
      3280 HBsAg, 2444 antiHBs and 3188 anti-HCV test results were reviewed,
      representing approximately 3% of the population of the city where the study was
      conducted. HBsAg, antiHBs and anti-HCV positivity were 3.2%, 36.12% and 0.97%,
      respectively. HBsAg and antiHBs positivity were higher among males (p<0.001).
      When assessed by age groups, HBsAg positivity was found to be the lowest in the
      age group 0-12 and highest in the age group 51-60. HBsAg positivity was lower in
      the post-NHPVP period versus pre-NHPVP period (p=0.01). Anti-HCV positivity was
      similar for pre- and post- NHPVP periods (p>0.05). CONCLUSION: Owing to the use
      of NHPVP, HBsAg seropositivity has decreased, and it is expected to decrease
      further in the next years with a wider implementation of the program. Efforts
      should be continued to increase the level of awareness in the community for HBV
      and the importance of immunization.

PMID- 27026762
TI  - Are We Late in the Diagnosis of Malignities Occurring in Solid Organ Transplant
      Patients? 11 Years' Experience.
AB  - OBJECTIVE: Our aim is to evaluate the frequency and characteristics of cancer in
      the population of patients with solid organ transplant who are under
      immunosuppressive medication. In this study we aimed to emphasize the importance
      of early diagnosis of cancer in solid organ transplant recipients. An aging
      population began to receive solid organ transplantation and survival times
      prolonged. But this had a cost and new problems came forward. Especially de novo
      cancers because of immunosuppressive therapy took notice. Risk of malignancy
      increases after organ transplantation and cancer incidence was about 2.3-3.1% in
      these patients including skin cancer, lung cancer, malign lymphoma, cervix
      cancer, kaposi sarcoma, and hepatobiliary cancer. MATERIALS AND METHODS: The
      files of 328 organ transplant recipients followed from January 2004 to April 2015
      at Ataturk University Medical Faculty were retrospectively reviewed. RESULTS:
      Eight patients developed cancer (2.4%). There were six males and two females. Age
      at cancer diagnosis ranged from 42 to 79 years old with average of 55 years. The
      interval from solid organ transplantation to cancer diagnosis ranged from 6
      months to 30 years. Among the patients, five were renal transplant recipients and
      two were liver transplant recipients. Four patients had stage IV disease, one
      patient stage IIIB, and three patients had stage I disease. For none of the
      patients a diagnosis with screening methods was used for cancer before any
      complaints of tumor emerged. CONCLUSION: To diagnose cancer at early stages in
      solid organ transplant recipients, earlier and detailed cancer screening is very
      important. The association between diagnosis of cancer at early stages and
      prolonged overall survival time is well known. Detailed and careful evaluation
      for occult malignancies in pre-transplantation period is also important.

PMID- 27026764
TI  - Which Measures of Health Status Assessment are the Most Significant in Organized
      Cohorts with Low Current Cardiovascular Risk? The Screening Study of Penitentiary
      Staff in Saratov Region, Russia.
AB  - OBJECTIVE: The aim of the present study was to compare different methods of
      health status assessment in organized cohort of penitentiary employees in Saratov
      Region, Russian Federation. MATERIALS AND METHODS: 1,014 penitentiary employees
      (81.8% male) aged 33.4+/-6.8 years were included in the cohort study. All
      participants underwent an annual preventive health examination in the Center of
      Medical and Social Rehabilitation of Russian Federal Penitentiary Service in
      Saratov Region. The prevalence of common cardiovascular risk factors was
      assessed. Risk Score and the number of fulfilled health metrics proposed by
      American Heart Association (AHA) were calculated for each participant. RESULTS:
      It is shown that penitentiary staff in Saratov Region is characterized by low
      current risk score (1.2+/-0.8%), but high prevalence of such risk factors as
      increased body weight and obesity (51%), tobacco use or passive smoking (81%),
      and unhealthy diet (55%). 98.4% of participants had the Score level of <=5%, but
      only 4.5% of penitentiary staff met the ideal cardiovascular health (they met all
      seven AHA health metrics). One fifth of the participants met three or less AHA
      health metrics. A statistically significant correlation between the risk Score
      and the number of fulfilled AHA health metrics is revealed (Chi-square = 5.1,
      p=0.024). The probability of fulfilment of less than 5 AHA health metrics in
      subjects with medium risk score is shown to be almost twofold greater than in
      subjects with low risk Score. However, there are a lot of differences in the
      assessment of cardiovascular health by risk Score and AHA health metrics.
      CONCLUSION: AHA health metrics are more preferable than the risk Score or
      assessment of separate cardiovascular risk factors for preventive management in
      organized cohorts with low current cardiovascular risk such as penitentiary staff
      in Saratov Region.

PMID- 27026765
TI  - Event-Related Potentials and the Stroop Effect.
AB  - In this manuscript, the researches on the Event-Related Potentials (ERP) elicited
      by the standard Stroop effect were reviewed. For the sake of clarity, only the
      parts of the manuscripts that reported the standard Stroop effect - ERPs relation
      were taken into consideration. 

PMID- 27026766
TI  - Ivy Sign in Moyamoya Disease.
AB  - Moyamoya disease is an idiopathic disease characterized by the progressive
      stenosis and collateral development of the distal internal carotid arteries. In
      this disease, several collateral vascular structures develop following stenosis
      and occlusion. The ivy sign is a characteristic Magnetic rezonance imaging (MRI)
      finding frequently encountered in patients with moyamoya. It can be observed both
      in post contrast T1-weighted images and Fluid attenuated inversion recovery
      (FLAIR) images. While this sign manifests in the form of contrasting on the
      cortical surfaces due to the formation of leptomeningeal collateral development
      and increased numbers of pial vascular webs on post contrast images, in FLAIR
      images it originates from the slow arterial flow in the leptomeningeal collateral
      vascular structures. In this case, we presented the Digital subtraction
      angiography (DSA) signs of moyamoya disease and "ivy sign" in MRI and its
      development mechanism in a 16 years old female patient. 

PMID- 27026767
TI  - Visual Hallucinations in an Old Patient after Cataract Surgery and Treatment.
AB  - Sensory visual pathologies, accompanying simple or complex visual hallucinations
      that occur in visually-impaired individuals due to ophthalmologic or brain
      pathologies related to visual pathways in patients without mental disorders, are
      defined as Charles Bonnet syndrome. Between 10% and 60% of the patients having
      age-related eye diseases involving retina, cornea and the lens, commonly with
      macular degeneration experience complex visual hallucinations depending on the
      severity of visual problems. The neurophysiology of the visual hallucinations in
      Charles Bonnet Syndrome is not clearly known, and they may differ in content and
      severity over time. In differential diagnoses of Charles Bonnet Syndrome, many
      aetiologies (drugs, uraemia, exposure to toxic materials, neurodegenerative and
      psychiatric conditions) need to be ruled out. In the treatment of Charles Bonnet
      syndrome, first the management of the reason of visual loss should be clarified
      if possible. If needed, neuroleptics, anticonvulsants, antidepressants,
      benzodiazepines, cognitive enhancer agents such as cholinesterase inhibitors can
      be used also. In this case, an 83-year-old female patient experiencing visual
      hallucinations as burning candles in both eyes' visual field after left eye
      cataract surgery, treated with 0.5 milligram/day risperidone will be presented. 

PMID- 27026768
TI  - Massive Pulmonary Embolism in a Patient with Heparin Induced Thrombocytopenia:
      Successful Treatment with Dabigatran.
AB  - Heparin induced thrombocytopenia (HIT) is a rare, potentially fatal, immune
      mediated complication of heparin therapy, associated with thrombosis and
      thrombocytopenia. In this study, a successful dabigatran administration in a case
      with massive pulmonary thromboembolism (mPTE) and HIT is presented. 57 years-old
      female, who was receiving low molecular weight heparin (LMWH) (0.4 mL once a
      daily, S.C. for 11 days) due to total knee replacement, was referred to our
      clinic with the hypotension and syncope attacks. Her echocardiography and
      pulmonary CT angiography findings were consistent with mPTE. We detected a
      serious decrease in her platelet count highly suggestive for HIT (plt:
      54*10(3)/uL). LMWH was discontinued and dabigatran was started (150 mg twice
      daily). After platelet count increased over 150*10(3)/MUL, dabigatran was
      switched to warfarin. Since heparin is widely used in medicine, all physicians
      need to be aware of this life threatening complication of heparin. Replacing
      heparin with an alternative anticoagulant such as dabigatran may become a life
      saving strategy especially in case of HIT complicated with mPTE. 

PMID- 27026769
TI  - Primary Pleomorphic Rhabdomyosarcoma of Thyroid Gland in an Adult Patient: A Case
      Report.
AB  - Thyroid sarcoma is a very rare entity, accounting for less than 1% of all
      malignant thyroid tumours. Rhabdomyosarcoma (RMS) is a sarcoma subtype, which is
      more common in children and adolescents. In this case, a 68-year old man,
      presented with hoarseness and diagnosed with pleomorphic RMS, was explored. No
      study of primary thyroid pure RMS has been reported in the literature, with the
      exception of the case reports of differentiated RMS. 

PMID- 27026770
TI  - A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene
      (c.241A>T) in Holt-Oram syndrome.
AB  - We report a case of a 31-year-old pregnant woman who was admitted to our
      perinatology outpatient clinic because of a fetal ventricular septal defect and
      limb reduction in the upper extremities of fetus revealed by ultrasonographic
      investigation diagnosed in the 16(th) week of gestation. First child of the
      family was diagnosed with Holt-Oram syndrome who had atrial septal defect and
      upper limb anomalies, whereas the father was documented to have arrhythmia and
      shortening of upper limbs. The pregnancy was terminated in the 16(th) week of
      gestation with the consent of the family. We performed mutation analysis in T-box
      transcription factor-5 (TBX5) gene coding exons, including exon/intron boundaries
      from peripheral blood or skin fibroblasts. The sequence analysis revealed c.241
      adenine (A)>thymine (T) [p. arginine (Arg) 81 Tryptophan (Trp)] alteration in
      exon-3 of the TBX5 gene in affected family members and fetus. This is a novel
      mutation causing Holt-Oram syndrome. 

PMID- 27026771
TI  - Efficacy and safety of post-cesarean section incisional infiltration with
      lidocaine and epinephrine versus lidocaine alone in reducing postoperative pain:
      A randomized controlled double-blinded clinical trial.
AB  - OBJECTIVE: Aim was to assess the efficacy and safety of incisional infiltration
      of lidocaine and epinephrine vs. lidocaine only to reduce postcesarean section
      (C/S) pain. MATERIAL AND METHODS: It was a prospective, randomized, controlled,
      double-blinded clinical trial that was conducted in two tertiary hospitals in
      Egypt and included 153 women undergoing C/S under general anesthesia. They were
      randomly divided into the following two groups: Group I (control group,
      number=78), in which the wound was infiltrated before skin closure with 20 mL of
      2% lidocaine, and Group II (study group, number=75), in which the wound was
      infiltrated before skin closure with 20 mL of 2% lidocaine and epinephrine. The
      primary outcomes were the time to first analgesic (TFA) request (minutes) and the
      postoperative pain scores that were measured using a visual analogue scale (VAS).
      The secondary outcomes included the duration of C/S, onset of mobilization, onset
      of breastfeeding, duration of hospital stay, local or systemic side effects of
      lidocaine and epinephrine, postoperative pyrexia, and postoperative wound
      infection. RESULTS: The pain score determined using VAS after 1 and 2 h was
      significantly decreased in Group II than in Group I. However, at 4.8 and 16 h,
      these results were significantly reversed in Group II than in Group I. The
      cumulative postoperative opioid consumption was significantly less in Group II
      than in Group I (50 vs. 90 mg). The onset of mobilization, onset of
      breastfeeding, and duration of hospital stay was significantly shorter in Group
      II than in Group I, whereas the TFA request was significantly longer in Group II.
      CONCLUSION: Administering epinephrine with 2% lidocaine prolongs the anesthetic
      effect and reduces the opioid analgesic dose postoperatively required, thereby
      enhancing patient recovery.

PMID- 27026772
TI  - Comparison of efficacy of metformin and oral contraceptive combination of ethinyl
      estradiol and drospirenone in polycystic ovary syndrome.
AB  - OBJECTIVE: The 2013 Endocrine Society guidelines state that hormonal
      contraceptives should be used for treating both menstrual irregularity and
      hirsutism in patients with polycystic ovary syndrome (PCOS). Metformin should be
      reserved for the treatment of women presenting with only menstrual irregularity
      because it has limited benefits in treating hyperandrogenism associated with
      PCOS. A high prevalence of insulin resistance is noted among the South Asians,
      and these guidelines may not hold good for this population. Thus, this study was
      conducted to investigate and compare the effects of metformin and an oral
      contraceptive containing drospirenone on menstrual pattern, body mass index,
      serum testosterone levels, and dehydroepiandrosterone sulfate (DHEAS) levels at
      baseline to 6 months of therapy in the treatment groups. MATERIAL AND METHODS:
      This was a prospective observational study that was conducted over a year in
      patients visiting the Endocrinology outpatient department at a tertiary care
      center in a south Indian city. Forty-six subjects diagnosed with PCOS as per the
      Rotterdam criteria were included. They received either metformin twice daily or
      an oral contraceptive containing drospirenone once daily as a monthly regimen for
      6 months. RESULTS: Metformin regularized menstrual cycles in 72% of patients who
      were followed up at 6 months. No significant difference was observed between the
      two treatment groups with respect to decreasing the body mass index, serum
      testosterone levels, and DHEAS levels (p=0.40, p=0.65, and p=0.22, respectively).
      CONCLUSION: Metformin is effective in regularizing menstrual cycles, decreasing
      body mass index, and treating hyperandrogenism in Indian women diagnosed with
      PCOS.

PMID- 27026773
TI  - German gynecologists' experience with a universal screening for gestational
      diabetes mellitus in daily practice: A qualitative study.
AB  - OBJECTIVE: In March 2012, a universal screening for gestational diabetes mellitus
      (GDM) was implemented in Germany. Despite international recommendations, a two
      step approach was introduced [step 1: 50-g glucose challenge test (GCT); if GCT
      is suspicious, step 2 follows: 75-g oral glucose tolerance test with (OGTT)].
      This qualitative study aimed at examining how gynecologists administer the
      screening for GDM in daily practice, whether they perceive any difficulties, and
      whether they have suggestions for improvement. MATERIAL AND METHODS: Seventeen
      resident gynecologists were interviewed face-to-face in semi-structured
      interviews. The interviews were recorded, transcribed verbatim, coded, and
      analyzed using qualitative content techniques. RESULTS: We revealed differences
      in the screening administration. Three gynecologists directly offered the second
      step of the two-step screening (OGTT) instead of completing the first step before
      offering the second step. These gynecologists only conducted GCT if the woman
      (with statutory health insurance) was not willing to pay for OGTT. Critique
      concerns the late introduction of billing codes, lack of information from
      official institutions, unavailability of readymade syrup with 50-g glucose, and
      lack of information material for pregnant women. CONCLUSION: Our results reflect
      that not all gynecologists appear to conduct the screening conforming to the
      maternity directive. However, this has to be validated in larger quantitative
      surveys. That some gynecologists directly conducted OGTT may fuel the discussion
      regarding the screening procedure. The two-step approach was already highly
      controversial at the time of introducing the screening because national and
      international organizations recommend a one-step approach. Therefore, our results
      are also relevant for other countries who have implemented a two-step screening
      and for countries planning to implement a screening.

PMID- 27026774
TI  - Reference range for uterine artery Doppler pulsatility index using transvaginal
      ultrasound at 20-24w6d of gestation in a low-risk Brazilian population.
AB  - OBJECTIVE: To establish reference range for uterine artery (UtA) Doppler
      pulsatility index (PI) using transvaginal ultrasound at 20-24w6d of gestation in
      a Brazilian population. MATERIAL AND METHODS: A retrospective cross-sectional
      study in 847 low-risk pregnant women undergoing routine second trimester
      ultrasound examination was conducted from February 2012 through March 2015. The
      mean UtA PI was calculated using color Doppler ultrasound with UtA gated at the
      level of the internal os. Mean+/-standard deviation and ranges for UtA Doppler PI
      in relation to gestational age (GA) are reported. Polynomial regression was used
      to obtain the best fit using mean UtA Doppler PI and GA (weeks) with adjustments
      performed using determination coefficient (R(2)). The 5(th), 50(th), and 95(th)
      percentiles for the mean UtA Doppler PI in relation to GA were determined.
      RESULTS: The mean UtA Doppler PI ranged from 1.14 at 20 weeks to 0.95 at 24 weeks
      of gestation. The best-fit curve of mean UtA Doppler PI as a function of GA was a
      first-degree polynomial regression: mean UtA Doppler PI=1.900-0.038*GA
      (R(2)=0.01). CONCLUSION: In summary, when the mean UtA PI Doppler values were
      measured by transvaginal ultrasound at 20-24w6d of gestation, decrease in UtA
      Doppler PI values with advancing GA was observed. Reference range for the mean
      UtA Doppler PI at 20-24w6d of gestation using the transvaginal ultrasound in a
      low-risk Brazilian population was established. We believe that this reference
      range may be of clinical value in daily obstetric practice.

PMID- 27026775
TI  - Utility of preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte
      ratios to distinguish malignant from benign ovarian masses.
AB  - OBJECTIVE: We aimed to investigate the utility of preoperative neutrophil-to
      lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte count
      as biomarkers to distinguish malignant from benign ovarian masses. MATERIAL AND
      METHODS: We retrospectively reviewed the histopathological results of 185 benign
      and 33 malignant cases following surgery for an initial diagnosis of adnexal mass
      and confirmed ovarian masses. Age, cancer antigen 125 (CA-125), white blood cell
      (WBC) count, hemoglobin (Hb), hematocrit (Hct), mean platelet volume (MPV),
      platelet distribution width (PDW), NLR, PLR, and lymphocyte counts were compared
      between groups. RESULTS: The significant diagnostic factors to distinguish
      malignant from benign disease were age (35.5+/-22 vs. 62+/-13 years; p<0.001) and
      CA-125 levels (16.6+/-21 vs. 98+/-366 U/mL; p<0.001). No significant difference
      was observed in WBC count, Hct, Hb, platelet count, PDW, and MPV between groups.
      To distinguish malignant from benign masses, lymphocyte count (1.29+/-0.91 vs.
      1.80+/-0.67*10(3) cells/MUL, p<0.001), NLR (4.95+/-5.36 vs. 3.32+/-2.72,
      p=0.024), and PLR (203.41+/-107.84 vs. 160.75+/-70.84, p<0.001) were identified
      as markers. The cutoff values were lymphocyte count of >1500 cells/MUL (p<0.001),
      NLR of 3.4732 (p=0.033), PLR of 161.13 (p<0.001), CA-125 of >40 U/mL (p<0.001),
      and age of >53 years (p<0.001); their respective sensitivity and specificity were
      66.7% and 77.8% [area under the curve (AUC), 0.723+/-0.055], 68.8% and 54.1%
      (AUC, 0.624+/-0.058), 81.8% and 50.8% (AUC, 0.683+/-0.052), 78.8% and 77.8% (AUC,
      0.797+/-0.057), and 81.8% and 82.2% (AUC, 0.888+/-0.025). Multiple logistic
      regression analysis revealed cutoff explanatory and accuracy values of 68.2% and
      94.9%, respectively, for lymphocyte count, NLR, PLR, CA-125, and age as
      independent parameters to distinguish malignant from benign ovarian masses.
      CONCLUSION: In combination with age and CA-125 levels, NLR, PLR, and lymphocyte
      count may be helpful to preoperatively distinguish malignant from benign ovarian
      masses.

PMID- 27026776
TI  - Changing trends in emergency peripartum hysterectomy in a tertiary obstetric
      center in Turkey during 2000-2013.
AB  - OBJECTIVE: To evaluate emergency peripartum hysterectomy (EPH) cases over a 14
      year period in a tertiary center in Istanbul, Turkey. MATERIAL AND METHODS: In
      this retrospective descriptive study, the records of all cases of EPH performed
      at the Zeynep Kamil Women and Children's Training and Research Hospital between
      January 2000 and January 2014 were analyzed. Results for 2000-2006 and 2007-2013
      were compared to identify changing trends. Demographic and clinical factors
      associated with EPH were assessed. RESULTS: During the 14-year study period, a
      total of 161,836 births occurred, out of which 104,783 (64.8%) were vaginal
      deliveries and 57,053 (35.2%) were cesarean section (CS). EPH was performed in 81
      patients with an overall incidence of 0.5 in 1000 deliveries. The EPH rate in
      2007-2013 (0.07%) was significantly higher than in 2000-2006 (0.03%). The major
      difference in the EPH populations between the two periods was the higher number
      of previous CS in 2007-2013 compared with 2000-2006 (p=0.01). Indications for EPH
      did not differ between the two periods. There were 7 (8.6%) maternal deaths in
      2000-2013, with significantly fewer maternal deaths in 2007-2013 than in 2000
      2006 (19.2% vs. 3.6%). CONCLUSION: Rate of EPH increased considerably from 2000
      to 2013. This increase was mostly related to the increasing rate of CS.
      Indications for EPH did not change over the study period, and the number of
      maternal deaths markedly decreased.

PMID- 27026777
TI  - In vitro chemosensitivity in ovarian carcinoma: Comparison of three leading
      assays.
AB  - OBJECTIVE: An alternative approach to the current therapy of ovarian carcinoma is
      the individualization of treatment by determining the sensitivity of tumoral
      tissue to chemotherapeutic agents before the initiation of chemotherapy. The
      objectives of the study are to determine the efficacy of in vitro
      chemosensitivity assays in ovarian carcinoma and to measure the correlation of
      three leading assays. MATERIAL AND METHODS: Fresh tumoral tissue samples of 26
      newly diagnosed primary ovarian cancer patients were studied with 3-(4,5-dimeth
      ylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) assay, adenosine
      triphosphate-tumor chemosensitivity assay (ATP-TCA) and differential staining
      cytotoxicity (DISC) assays. Chemosensitivity of tumors were studied for
      paclitaxel, carboplatin, docetaxel, topotecan, gemcitabine, and doxorubicin with
      each of the three assays. Subgroup analysis was performed for stage, grade, and
      histologic type. RESULTS: The in vitro chemosensitivity results of MTT, ATP, and
      DISC assays were found to be similar. The subgroups in which in vitro assays
      would be more useful were encountered for patients with advanced stage and serous
      histology ovarian carcinoma. CONCLUSIONS: In vitro chemosensitivity can be
      determined in ovarian carcinoma with ATP, MTT, or DISC assays before the
      initiation of chemotherapy. These three assays correlate well with each other and
      are particularly useful for serous and advanced cancers. Large prospective
      studies comparing standard versus assay-directed therapy with an endpoint of
      overall survival are required before routine clinical utilization of these
      assays.

PMID- 27026778
TI  - Hypodontia and ovarian cancer: A systematic review.
AB  - Hypodontia can be defined as the non-formation of one or more teeth during the
      developmental period. Mutation in several genes related to tooth formation has
      previously been correlated with cancer. Regarding the ovarian cancer, there are
      few studies that associate the presence of hypodontia with ovarian cancer. A
      systematic literature search was performed in PubMed and Scopus. In total, 385
      patients were included in this study. Control group was present in 3 out of 4
      studies (340 patients). Hypodontia was present in 56 out of 290 patients
      (incidence of 19.3%). Only in 2 out of 4 studies, the number of missing teeth was
      mentioned (47 teeth), while the majority of them were either maxillary second
      premolars or maxillary lateral incisors. Unilateral distribution of the missing
      teeth was present in 28 out of 46 patients, while bilateral distribution of the
      missing teeth was present in 18 out of 46 patients. The presence of ovarian
      cancer in the family medical history occurred in 12 out of 33 patients. Only 1
      out of 4 studies examined the presence of genes with mutations in the included
      patients. Based on our findings, the lack of clinical studies was the principal
      obstacle to clarify the possible predictive value of hypodontia in the early
      prediction of patients with higher risk of ovarian cancer. 

PMID- 27026779
TI  - Inherited thrombophilia and reproductive disorders.
AB  - Apart from its established role in the pathogenesis of venous thromboembolism
      (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy
      loss and vascular gestational complications. There is a lot of controversy in the
      literature on the relationship between inherited prothrombotic defects and these
      obstetric complications. This is a review of the literature on inherited
      thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A
      mutation, and protein S deficiency seem to be associated with late and recurrent
      early pregnancy loss, while their impact on other pregnancy complications is
      conflicting. No definite association has been established between protein C and
      antithrombin deficiency and adverse pregnancy outcome, primarily due to their low
      prevalence. Screening is suggested only for women with early recurrent loss or
      late pregnancy loss. Anticoagulant treatment during pregnancy should be
      considered for women with complications who were tested positive for
      thrombophilia. 

PMID- 27026780
TI  - Pelvic recurrence of stage 1a well-differentiated endometrial carcinoma after 13
      years: A case report.
AB  - A great majority of endometrial carcinoma recurrences are observed in high-risk
      patients and within the first 3 years of treatment. The relapse of endometrial
      carcinoma occurring more than 10 years after initial treatment has rarely been
      described. Initially diagnosed and treated for International Federation of
      Gynecology and Obstetrics (FIGO) stage 1a, grade 1 adenocarcinoma, our patient
      presented 13 years later with an isolated pelvic recurrence, demonstrating, to
      our knowledge, the longest disease-free interval with recurrence in the pelvis
      reported in literature. After surgical resection, the patient is being considered
      for enrollment in a clinical trial. Despite favorable prognostic features, it is
      possible to observe the recurrence of endometrial carcinoma even 5 years after
      surveillance and remission. Successful salvage therapies are available but may
      depend upon early diagnosis. 

PMID- 27026781
TI  - What is your diagnosis?

PMID- 27026782
TI  - Letters to the Editor.

PMID- 27026783
TI  - Erratum.
AB  - [This corrects the article on p. 272 in vol. 15, PMID: 26413003.]. 

PMID- 27026784
TI  - Bioethics in Practice: Ochsner Clinical School Students Speak the Language of
      Virtues.

PMID- 27026785
TI  - Clinical Images: Lemierre Syndrome: The Forgotten Disease?

PMID- 27026787
TI  - 16th Annual Southern Hospital Medicine Conference Abstracts.
AB  - CLINICAL VIGNETTES ABSTRACTS e3-e38 QUALITY INNOVATIONS-RESEARCH ABSTRACTS e38
      e42. 

PMID- 27026786
TI  - The Future of Medical Education: Flipping the Classroom and Education Technology.

PMID- 27026788
TI  - 7th Annual Evidence-Based Practice/Research Conference Abstracts.
AB  - General Session Abstracts G1-G8 Poster Abstracts P1-P8. 

PMID- 27026790
TI  - Abbreviations/Acronyms.

PMID- 27026789
TI  - Overview of the Alliance of Independent Academic Medical Centers National
      Initiative.

PMID- 27026792
TI  - Draft Genome Sequence of Providencia sneebia Strain ST1, a Quorum Sensing
      Bacterium Associated with Marine Microalgae.
AB  - Providencia sneebia strain ST1 is a symbiotic bacterium (belonging to phylum
      gammaproteobacteria) with marine microalgae. This bacterium exhibits the ability
      to produce N-Acyl homoserine lactone signal molecule. To date, no genome that
      originates from marine Providencia spp. has been reported. In this study, we
      present the genome sequence of this strain. It has a genome size of 4.89 M, with
      19 contigs and an average G+C of 51.97%. The function of 4,631 proteins was
      predicted, and 3,652 proteins were assigned to COG functional categories. Among
      them, 407 genes are involved in carbohydrate metabolism, 306 genes participate in
      nitrogen utilization and energy conversion, and 185 genes related to signal
      transduction process. Thus, this strain plays an active role in the
      biogeochemical cycle in algal life history. The whole-genome of this isolate and
      annotation will help enhance understanding of bacterial ecological behavior in
      the phycosphere. 

PMID- 27026793
TI  - Assessment of Semiquantitative Parameters of Dynamic Contrast-Enhanced Perfusion
      MR Imaging in Differentiation of Subtypes of Renal Cell Carcinoma.
AB  - BACKGROUND: To assess semiquantitative parameters of dynamic contrast-enhanced
      perfusion MR imaging (DCE) in differentiation of subtypes of renal cell carcinoma
      (RCC). MATERIAL/METHODS: Prospective study conducted upon 34 patients (27 M, 7 F,
      aged 25-72 ys: mean 45 ys) with RCC. Abdominal dynamic contrast-enhanced gradient
      recalled echo MR sequence after administration of gadopentetate dimeglumine was
      obtained. The time signal intensity curve (TIC) of the lesion was created with
      calculation of enhancement ratio (ER), and washout ratio (WR). RESULTS: The
      subtypes of RCC were as follows: clear cell carcinomas (n=23), papillary
      carcinomas (n=6), and chromophobe carcinomas (n=5). The mean ER of clear cell,
      papillary and chromophobe RCC were 188+/-49.7, 35+/-8.9, and 120+/-41.6
      respectively. The mean WR of clear cell, papillary and chromophobe RCCs were
      28.6+/-6.8, 47.6+/-5.7 and 42.7+/-10, respectively. There was a significant
      difference in ER (P=0.001) and WR (P=0.001) between clear cell RCC and other
      subtypes of RCC. The threshold values of ER and WR used for differentiating clear
      cell RCC from other subtypes of RCC were 142 and 38 with areas under the curve of
      0.937 and 0.895, respectively. CONCLUSIONS: We concluded that ER and WR are
      semiquantitative perfusion parameters useful in differentiation of clear cell RCC
      from chromophobe and papillary RCCs.

PMID- 27026794
TI  - Quantitative Assessment of Left Ventricular Function and Myocardial Mass: A
      Comparison of Coronary CT Angiography with Cardiac MRI and Echocardiography.
AB  - BACKGROUND: The purpose of this study was to compare the left ventricular
      parameters obtained from multi-detector row computed tomography (MDCT) studies
      with two-dimensional echocardiography (2DE), and magnetic resonance imaging
      (MRI), which is accepted as the gold standard in the evaluation of left
      ventricular functions. The study also aimed to evaluate whether or not there is a
      relationship between the MR-Argus and CMR tools software programs which are used
      in post-process calculations of data obtained by MRI. MATERIAL/METHODS: Forty
      patients with an average age of 51.4+/-14.9 years who had been scanned with
      cardiac MDCT were evaluated with cardiac MRI and 2DE. End-diastolic volume (EDV),
      end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac
      output (CO), and myocardial mass values calculated by MDCT, MRI, and 2DE were
      compared with each other. Two different MR software programs were used to compare
      left ventricular functions. The CMR tools LV tutorials method is accepted as the
      gold standard because it can be used in three-dimensional functional evaluation.
      The Pearson Correlation and Bland-Altman analysis were performed to compare the
      results from the two MR methods (MR-Argus and CMR tools) and the results from
      both the MDCT and the 2DE with the CMR tools results. RESULTS: Strong positive
      correlations for EF values were found between the MDCT and CMR tools (r=0.702
      p<0.001), and between the MR-Argus and CMR tools (r=0.746 p<0.001). The
      correlation between the 2DE and CMR tools (r=0.449 p<0.004), however, was only
      moderate. Similar results were obtained for the other parameters. The strongest
      correlation for ESV, EDV, and EF was between the two MR software programs. The
      correlation coefficient between the MDCT and CMR tools is close to the
      correlation coefficient between the two software programs. While the correlation
      between 2DE and CMR tools was satisfactory for ESV, EDV, and CO values, it was at
      a moderate level for the other parameters. CONCLUSIONS: Left ventricular
      functional analysis can be performed easily and reliably with cardiac MDCT used
      for coronary artery evaluation and it also gives more accurate results than 2DE.

PMID- 27026795
TI  - Gd-EOB-DTPA-Enhanced MR Imaging of the Liver: The Effect on T2 Relaxation Times
      and Apparent Diffusion Coefficient (ADC).
AB  - BACKGROUND: To investigate the effect of gadoxetic acid disodium (Gd-EOB-DTPA) on
      T2 relaxation times and apparent diffusion coefficient (ADC) values of the liver
      and focal liver lesions on a 1.5-T system. MATERIAL/METHODS: Magnetic resonance
      (MR) studies of 50 patients with 35 liver lesions were retrospectively analyzed.
      All examinations were performed at 1.5T and included T2-weighted turbo spin-echo
      (TSE) and diffusion-weighted (DW) images acquired before and after intravenous
      administration of Gd-EOB-DTPA. To assess the effect of this hepatobiliary
      contrast agent on T2-weighted TSE images and DW images T2 relaxation times and
      ADC values of the liver and FLLs were calculated and compared pre- and post
      injection. RESULTS: The mean T2 relaxation times of the liver and focal hepatic
      lesions were lower on enhanced than on unenhanced T2-weighted TSE images
      (decrease of 2.7% and 3.6% respectively), although these differences were not
      statistically significant. The mean ADC values of the liver showed statistically
      significant decrease (of 4.6%) on contrast-enhanced DW images, compared to
      unenhanced images (P>0.05). The mean ADC value of liver lesions was lower on
      enhanced than on unenhanced DW images, but this difference (of 2.9%) did not
      reach statistical significance. CONCLUSIONS: The mean T2 relaxation times of the
      liver and focal liver lesions as well as the mean ADC values of liver lesions
      were not significantly different before and after administration of Gd-EOB-DTPA.
      Therefore, acquisition of T2-weighted and DW images between the dynamic contrast
      enhanced examination and hepatobiliary phase is feasible and time-saving.

PMID- 27026796
TI  - Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology
      Assessment.
AB  - BACKGROUND: Intrathecal drug delivery systems can be used to manage refractory or
      persistent cancer pain. We investigated the benefits, harms, cost-effectiveness,
      and budget impact of these systems compared with current standards of care for
      adult patients with chronic pain due owing to cancer. METHODS: We searched Ovid
      MEDLINE, Ovid Embase, the Cochrane Library databases, National Health Service's
      Economic Evaluation Database, and Tufts Cost-Effectiveness Analysis Registry from
      January 1994 to April 2014 for evidence of effectiveness, harms, and cost
      effectiveness. We used existing systematic reviews that had employed reliable
      search and screen methods and searched for studies published after the search
      date reported in the latest systematic review to identify studies. Two reviewers
      screened records and assessed study validity. The cost burden of publicly funding
      intrathecal drug delivery systems for cancer pain was estimated for a 5-year
      timeframe using a combination of published literature, information from the
      device manufacturer, administrative data, and expert opinion for the inputs.
      RESULTS: We included one randomized trial that examined effectiveness and harms,
      and one case series that reported an eligible economic evaluation. We found very
      low quality evidence that intrathecal drug delivery systems added to
      comprehensive pain management reduce overall drug toxicity; no significant
      reduction in pain scores was observed. Weak conclusions from economic evidence
      suggested that intrathecal drug delivery systems had the potential to be more
      cost-effective than high-cost oral therapy if administered for 7 months or
      longer. The cost burden of publicly funding this therapy is estimated to be
      $100,000 in the first year, increasing to $500,000 by the fifth year.
      CONCLUSIONS: Current evidence could not establish the benefit, harm, or cost
      effectiveness of intrathecal drug delivery systems compared with current
      standards of care for managing refractory cancer pain in adults. Publicly funding
      intrathecal drug delivery systems for cancer pain would result in a budget impact
      of several hundred thousand dollars per year.

PMID- 27026797
TI  - Intrathecal Drug Delivery Systems for Noncancer Pain: A Health Technology
      Assessment.
AB  - BACKGROUND: Intrathecal drug delivery systems can be used to manage refractory or
      persistent chronic nonmalignant (noncancer) pain. We investigated the benefits,
      harms, cost-effectiveness, and budget impact of these systems compared with
      current standards of care for adult patients with chronic pain owing to
      nonmalignant conditions. METHODS: We searched Ovid MEDLINE, Ovid Embase, the
      Cochrane Library, and the National Health Service's Economic Evaluation Database
      and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014
      for evidence of effectiveness, harms, and cost-effectiveness. We used existing
      systematic reviews that had employed reliable search and screen methods and also
      searched for studies published after the search date reported in the latest
      systematic review to identify studies. Two reviewers screened records and
      assessed study validity. RESULTS: We found comparative evidence of effectiveness
      and harms in one cohort study at high risk of bias (>= 3-year follow-up, N =
      130). Four economic evaluations of low to very low quality were also included.
      Compared with oral opioid analgesia alone or a program of analgesia plus
      rehabilitation, intrathecal drug delivery systems significantly reduced pain (27%
      additional improvement) and morphine consumption. Despite these reductions,
      intrathecal drug delivery systems were not superior in patient-reported well
      being or quality of life. There is no evidence of superiority of intrathecal drug
      delivery systems over oral opioids in global pain improvement and global
      treatment satisfaction. Comparative evidence of harms was not found. Cost
      effectiveness evidence is of insufficient quality to assess the appropriateness
      of funding intrathecal drug delivery systems. Evidence comparing intrathecal drug
      delivery systems with standard care was of very low quality. CONCLUSIONS: Current
      evidence does not establish (or rule out) superiority or cost-effectiveness of
      intrathecal drug delivery systems for managing chronic refractory nonmalignant
      pain. The budget impact of funding intrathecal drug delivery systems would be
      between $1.5 and $5.0 million per year.

PMID- 27026798
TI  - Left Ventricular Assist Devices for Destination Therapy: A Health Technology
      Assessment.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) provide circulatory support
      to assist the damaged left ventricle in patients with end-stage heart failure.
      Implantation of an LVAD is sometimes a last resort for patients with end stage
      heart failure who are ineligible for heart transplantation (destination therapy).
      First-generation LVADs used pulsatile pumps to mimic the natural pulsing action
      of the heart. Implanted second-generation LVADs use a rapidly spinning rotor to
      produce a continuous flow of blood into the systemic arterial system. OBJECTIVES:
      Our objectives were to: Determine the clinical effectiveness of LVADs for
      destination therapy for patients with end-stage heart failure who are ineligible
      for heart transplantationEstimate the cost-effectiveness of destination-therapy
      LVAD for patients with end-stage heart failure who are ineligible for heart
      transplantation and to estimate the potential budget impact for the Ontario
      Ministry of Health and Long-Term Care over the next 5 years. METHODS: We
      performed a narrative review of the clinical and economic literature for
      effectiveness and cost-effectiveness and a budget impact analysis from the
      perspective of the Ministry of Health and Long-Term Care. We did not conduct a
      meta-analysis of the clinical evidence owing to differences in the type of LVADs
      included in the studies. RESULTS: Three systematic reviews and one observational
      study contributed to the clinical evidence. Three economic reviews contributed to
      the economic evidence. There is moderate quality evidence that treatment with
      continuous-flow LVADs improves survival but has higher adverse events rates
      compared with drug therapy. Low quality evidence suggests treatment with a
      continuous-flow LVADs improves quality of life. The incremental cost
      effectiveness ratio associated with destination-therapy LVAD over optimal medical
      management is relatively high and exceeds the traditionally accepted thresholds
      ($50,000 to $100,000 per quality-adjusted life-year). The estimated net budget
      impact is $13.6 million in 2015, $20.7 million in 2016, $27.8 million in 2017,
      $35.8 million in 2018, and $45.0 million in 2019. CONCLUSIONS: For patients with
      end-stage heart failure who are ineligible for heart transplantation, permanent
      treatment with continuous-flow LVADs is effective at improving survival and
      quality of life compared with drug therapy. However, permanent continuous-flow
      devices have higher adverse event rates than drug therapy. Although it improves
      survival and quality of life, the device itself and the surgery to implant it are
      very expensive.

PMID- 27026799
TI  - Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health
      Technology Assessment.
AB  - BACKGROUND: In Ontario, current treatment for eligible patients who have an acute
      ischemic stroke is intravenous thrombolysis (IVT). However, there are some
      limitations and contraindications to IVT, and outcomes may not be favourable for
      patients with stroke caused by a proximal intracranial occlusion. An alternative
      is mechanical thrombectomy with newer devices, and a number of recent studies
      have suggested that this treatment is more effective for improving functional
      independence and clinical outcomes. The objective of this health technology
      assessment was to evaluate the clinical effectiveness and cost-effectiveness of
      new-generation mechanical thrombectomy devices (with or without IVT) compared to
      IVT alone (if eligible) in patients with acute ischemic stroke. METHODS: We
      conducted a systematic review of the literature, limited to randomized controlled
      trials that examined the effectiveness of mechanical thrombectomy using stent
      retrievers and thromboaspiration devices for patients with acute ischemic stroke.
      We assessed the quality of the evidence using the GRADE approach. We developed a
      Markov decision-analytic model to assess the cost-effectiveness of mechanical
      thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated
      incremental cost-effectiveness ratios using a 5-year time horizon, and conducted
      sensitivity analyses to examine the robustness of the estimates. RESULTS: There
      was a substantial, statistically significant difference in rate of functional
      independence (GRADE: high quality) between those who received mechanical
      thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95%
      confidence interval [CI] 1.88-3.04). We did not observe a difference in mortality
      (GRADE: moderate quality) (OR 0.80, 95% CI 0.60-1.07) or symptomatic
      intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66-1.87).
      In the base-case cost-utility analysis, which had a 5 year time horizon, the
      costs and effectiveness for mechanical thrombectomy were $126,939 and 1.484
      quality-adjusted life-years (QALYs) (2.969 life-years). The costs and
      effectiveness for IVT alone were $124,419 and 1.273 QALYs (2.861 life-years),
      respectively. Mechanical thrombectomy was associated with an incremental cost
      effectiveness ratio of $11,990 per QALY gained. Probabilistic sensitivity
      analysis showed that the probability of mechanical thrombectomy being cost
      effective was 57.5%, 89.7%, and 99.6%, at thresholds of $20,000, $50,000, and
      $100,000 per QALY gained, respectively. We estimated that adopting mechanical
      thrombectomy would lead to a cost increase of approximately $1 to 2 million.
      CONCLUSIONS: High quality evidence showed that mechanical thrombectomy
      significantly improved functional independence and appeared to be cost-effective
      compared to IVT alone for patients with acute ischemic stroke.

PMID- 27026800
TI  - Perioperative blood loss in total hip and knee arthroplasty: Outcomes associated
      with intravenous tranexamic acid use in an academic medical center.
AB  - OBJECTIVES: Clinical trials have reported decreased blood loss with the use of
      tranexamic acid during joint reconstruction. The purpose of this study was to
      assess the individual practice implications of tranexamic acid use in joint
      replacement surgery. METHODS: Health records of adults undergoing total knee
      arthroplasty and total hip arthroplasty over a 12-month period were
      retrospectively reviewed. The treatment group comprised patients who received
      intravenous tranexamic acid perioperatively. The control group comprised patients
      who did not receive tranexamic acid. RESULTS: Patients in the treatment group (n
      = 64) and the control group (n = 99) were well matched for demographics,
      orthopedic diagnosis, and comorbidities. In-hospital postsurgical mean decreases
      in hemoglobin concentrations were -4.05 g/dL and -4.94 g/dL in the treatment and
      control groups, respectively (p < 0.001). Postsurgical mean decreases in
      hematocrit levels were -11.2% and -14.2% in the treatment and control groups,
      respectively (p < 0.001). Three patients in the treatment group (5%) and 21
      patients in the control group (21%) received red blood cell transfusions (p =
      0.006). As compared to control, the relative risk of transfusion in the treatment
      group was 0.23 (95% confidence interval = 0.07-0.76) and the number needed to
      treat to avoid one transfusion was 7.0 (95% confidence interval = 3.8-14.4). No
      evidence of thromboembolism or other serious complications were observed in
      either group. CONCLUSIONS: In patients undergoing joint replacement surgery,
      perioperative administration of tranexamic acid was associated with diminished
      blood loss and lesser resource utilization.

PMID- 27026801
TI  - Effects of medication adherence on hospitalizations and healthcare costs in
      patients with schizophrenia in Thailand.
AB  - BACKGROUND: This study was conducted to determine the impacts of medication
      adherence on hospitalization and direct healthcare cost in patients with
      schizophrenia in Thailand. METHODS: A retrospective study was undertaken.
      Patients with schizophrenia aged 18-65 years who visited a University hospital
      and received antipsychotics from April 2011 to October 2011 were included.
      Propensity score-adjusted logistic regression was used to determine the impacts
      of medication adherence on schizophrenia-related and all-cause hospitalizations.
      RESULTS: A total of 582 patients were included. Three out of 224 patients (1.3%)
      were hospitalized with schizophrenia in optimal adherence group, while 10 of 140
      (7.1%) were hospitalized in under-adherence group, and 7 of 218 (3.2%) were
      hospitalized in over-adherence group. Based on propensity score-adjusted
      multivariate logistic regression, the adjusted odds ratio was 5.86 (95%
      confidence interval = 1.53-22.50) for schizophrenia-related hospitalization and
      8.04 (95% confidence interval = 2.20-29.40) for all-cause hospitalization. The
      average annual direct healthcare costs in patients with optimal adherence, under
      adherence, and over-adherence were US$371 +/- US$836, US$386 +/- US$734, and
      US$508 +/- US$2168, respectively. CONCLUSION: An initiation of interventions to
      maintain optimal adherence in patients with schizophrenia would significantly
      impact the healthcare system.

PMID- 27026802
TI  - What is the effect of nicotinic acetylcholine receptor stimulation on
      osteoarthritis in a rodent animal model?
AB  - OBJECTIVES: Despite the rising number of patients with osteoarthritis, no
      sufficient chondroprotective and prophylactic therapy for osteoarthritis has been
      established yet. The purpose of this study was to verify whether stimulation of
      the nicotinic acetylcholine receptor via nicotine has a beneficial effect on
      cartilage degeneration in the development of osteoarthritis and is capable of
      reducing the expression of proinflammatory cytokines and cartilage degrading
      enzymes in synovial membranes after osteoarthritis induction. METHODS:
      Experimental osteoarthritis was induced in Lewis rats using a standardized
      osteoarthritis model with monoiodoacetate. A total of 16 Lewis rats were
      randomized into four groups: control, sham + nicotine application,
      osteoarthritis, and osteoarthritis + nicotine application. Nicotine (0.625 mg/kg
      twice daily) was administered intraperitoneally for 42 days. We analyzed
      histological sections, radiological images and the expression of the
      proinflammatory cytokines, such as interleukin-1beta, tumor necrosis factor-alpha
      and interleukin-6, and of matrix metalloproteases 3, 9 and 13 and tissue
      inhibitors of metalloprotease-1 in synovial membranes via quantitative polymerase
      chain reaction. RESULTS: Histological and x-ray examination revealed cartilage
      degeneration in the osteoarthritis group compared to control or sham + nicotine
      groups (histological control vs osteoarthritis: p = 0.002 and x-ray control vs
      osteoarthritis: p = 0.004). Nicotine treatment reduced the cartilage degeneration
      without significant differences. Osteoarthritis induction led to a higher
      expression of proinflammatory cytokines and matrix metalloproteases as compared
      to control groups. This effect was attenuated after nicotine administration. The
      differences of proinflammatory cytokines and matrix metalloproteases did not
      reach statistical significance. CONCLUSION: With the present small-scale study,
      we could not prove a positive effect of nicotinic acetylcholine receptor
      stimulation on osteoarthritis due to a conservative statistical analysis and the
      consecutive lack of significant differences. Nevertheless, we found promising
      tendencies of relevant parameters that might prompt further experiments designed
      to evaluate the potency of stimulation of this receptor system as an additional
      treatment approach for osteoarthritis.

PMID- 27026803
TI  - Economic analysis of temperature-controlled laminar airflow (TLA) for the
      treatment of patients with severe persistent allergic asthma.
AB  - INTRODUCTION: Chronic asthma is a significant burden for individual sufferers,
      adversely impacting their quality of working and social life, as well as being a
      major cost to the National Health Service (NHS). Temperature-controlled laminar
      airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on
      treatment option that is non-invasive and has been shown in clinical studies to
      improve quality of life for patients with poorly controlled allergic asthma. The
      objective of this study was to quantify the cost-effectiveness of TLA (Airsonett
      AB) technology as an add-on to standard asthma management drug therapy in the UK.
      METHODS: The main performance measure of interest is the incremental cost per
      quality-adjusted life year (QALY) for patients using TLA in addition to usual
      care versus usual care alone. The incremental cost of TLA use is based on an
      observational clinical study monitoring the incidence of exacerbations with
      treatment valued using NHS cost data. The clinical effectiveness, used to derive
      the incremental QALY data, is based on a randomised double-blind placebo
      controlled clinical trial comprising participants with an equivalent asthma
      condition. RESULTS: For a clinical cohort of asthma patients as a whole, the
      incremental cost-effectiveness ratio (ICER) is L8998 per QALY gained, that is,
      within the L20 000/QALY cost-effectiveness benchmark used by the National
      Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates
      that ICER values range from L18 883/QALY for the least severe patients through to
      TLA being dominant, that is, cost saving as well as improving quality of life,
      for individuals with the most severe and poorly controlled asthma. CONCLUSIONS:
      Based on our results, Airsonett TLA is a cost-effective addition to treatment
      options for stage 4/5 patients. For high-risk individuals with more severe and
      less well controlled asthma, the use of TLA therapy to reduce incidence of
      hospitalisation would be a cost saving to the NHS.

PMID- 27026804
TI  - Evaluation of inhaler handling-errors, inhaler perception and preference with
      Spiromax, Easyhaler and Turbuhaler devices among healthy Finnish volunteers: a
      single site, single visit crossover study (Finhaler).
AB  - INTRODUCTION: Correct inhaler technique and device preference are positively
      correlated with improved adherence and clinical outcomes. This study was designed
      to investigate inhaler technique mastery and device preference for three
      different dry powder inhalers, Spiromax, Easyhaler and Turbuhaler. METHODS: This
      was a single site, single visit, crossover study assessing device mastery,
      handling errors and preference using empty Spiromax, Easyhaler and Turbuhaler
      devices in healthy adult Finnish volunteers. Inhaler naive adult participants
      were observed by healthcare professionals (HCPs) to evaluate the proportion of
      participants achieving device mastery (defined as an absence of HCP observed
      errors) using a three-step approach: (1) intuitive use (with no instructions),
      (2) after reading the patient information leaflet and (3) after HCP instruction.
      HCPs monitored and recorded errors based on device-specific handling error
      checklists. At the end of the study, participants completed a device preference
      questionnaire and rated their satisfaction with the three devices. RESULTS:
      Spiromax was correctly used by 37.5% and 93.3% of participants in steps 1 and 2,
      respectively, compared with 0% and 58.3% with Easyhaler, and 9.2% and 76.7% with
      Turbuhaler. All three devices showed high mastery (>95%) in step 3. The most
      common error reported with Spiromax was related to the orientation of the device.
      Not shaking the device was the most common error with Easyhaler. Errors in
      priming the device were the most common with Turbuhaler. Spiromax, Easyhaler and
      Turbuhaler were rated as the 'easiest device to use' by 73.1%, 12.6% and 14.3% of
      participants, respectively. The HCP instructions clearly improved the use of all
      devices. CONCLUSION: Higher levels of device mastery, including intuitive/ease of
      use, were reported by naive users when using Spiromax compared with Easyhaler and
      Turbuhaler.

PMID- 27026805
TI  - Validation of a metered dose inhaler electronic monitoring device: implications
      for asthma clinical trial use.
AB  - BACKGROUND: The SmartTouch Ventolin monitor (Adherium, Auckland, New Zealand) is
      an electronic monitor for use with a Ventolin metered dose inhaler, which records
      the date and time of inhaler actuations. This technology has the potential to
      allow in-depth analysis of patterns of inhaler use in clinical trial settings.
      The aim of this study was to determine the accuracy of the SmartTouch Ventolin
      monitor in recording Ventolin actuations. METHODS: 20 SmartTouch Ventolin
      monitors were attached to Ventolin metered dose inhalers. Bench testing was
      performed over a 10-week period, to reflect the potential time frame between
      visits in a clinical trial. Inhaler actuations were recorded in a paper diary,
      which was compared with data uploaded from the monitors. RESULTS: 2560 actuations
      were performed during the 10-week study period. Monitor sensitivity for diary
      recorded actuations was 99.9% with a lower 97.5% confidence bound of 99.7%. The
      positive predictive value for diary-recorded actuations was 100% with a 97.5%
      lower confidence bound of 99.9%. CONCLUSIONS: The SmartTouch Ventolin monitor is
      highly accurate in recording and retaining electronic data. It can be recommended
      for use in clinical trial settings in which training and quality control systems
      are incorporated into study protocols to ensure accurate data acquisition.

PMID- 27026806
TI  - British Thoracic Society/Intensive Care Society Guideline for the ventilatory
      management of acute hypercapnic respiratory failure in adults.

PMID- 27026807
TI  - A role of the adaptive immune system in glucose homeostasis.
AB  - OBJECTIVE: The immune system, including the adaptive immune response, has
      recently been recognized as having a significant role in diet-induced insulin
      resistance. In this study, we aimed to determine if the adaptive immune system
      also functions in maintaining physiological glucose homeostasis in the absence of
      diet-induced disease. RESEARCH DESIGN AND METHODS: SCID mice and immunocompetent
      control animals were phenotypically assessed for variations in metabolic
      parameters and cytokine profiles. Additionally, the glucose tolerance of SCID and
      immunocompetent control animals was assessed following introduction of a high-fat
      diet. RESULTS: SCID mice on a normal chow diet were significantly insulin
      resistant relative to control animals despite having less fat mass. This was
      associated with a significant increase in the innate immunity-stimulating
      cytokines granulocyte colony-stimulating factor, monocyte chemoattractant protein
      1 (MCP1), and MCP3. Additionally, the SCID mouse phenotype was exacerbated in
      response to a high-fat diet as evidenced by the further significant progression
      of glucose intolerance. CONCLUSIONS: These results support the notion that the
      adaptive immune system plays a fundamental biological role in glucose
      homeostasis, and that the absence of functional B and T cells results in
      disruption in the concentrations of various cytokines associated with macrophage
      proliferation and recruitment. Additionally, the absence of functional B and T
      cells is not protective against diet-induced pathology.

PMID- 27026808
TI  - Vitamin D for the treatment of painful diabetic neuropathy.
AB  - OBJECTIVE: To assess the effect of high-dose vitamin D in patients with painful
      diabetic neuropathy. METHODS: A single intramuscular dose of 600 000 IU vitamin D
      was administered, and the effects on metabolic parameters and neuropathic pain
      assessed over 20 weeks. RESULTS: 143 participants with predominantly type 2
      diabetes, aged 52.31+/-11.48 years, with a Douleur Neuropathique 4 (DN4) score
      (3.0+/-1.8), total McGill pain score (21.2+/-14.9), and Short Form McGill Pain
      Questionnaire (SFMPQ) score (2.1+/-0.9), were enrolled. The baseline 25
      hydroxyvitamin D (25(OH)D) level was 31.7+/-23.3 ng/mL and 58 (40.5%) patients
      showed evidence of vitamin D deficiency (25(OH)D<20 ng/mL). Intramuscular
      administration of vitamin D resulted in a significant increase in 25(OH)D (46.2+/
      10.2 ng/mL, p<0.0001) and a reduction in positive symptoms on the DN4 (p<0.0001),
      total pain score (p<0.0001), and SFMPQ (p<0.0001). CONCLUSIONS: Treatment with a
      single intramuscular dose of 600 000 IU of vitamin D in patients with painful
      diabetic neuropathy is associated with a significant decrease in the symptoms of
      painful diabetic neuropathy. TRIAL REGISTRATION NUMBER: BIDE-12/2014.

PMID- 27026809
TI  - Indirect measure of visceral adiposity 'A Body Shape Index' (ABSI) is associated
      with arterial stiffness in patients with type 2 diabetes.
AB  - OBJECTIVE: Among indirect measures of visceral adiposity, A Body Shape Index
      (ABSI), which is defined as waist circumference (WC)/(body mass index
      (BMI)(2/3)*height(1/2)), is unique in that ABSI is positively correlated with
      visceral adiposity and is supposed to be independent of BMI. ABSI has been also
      shown to be linearly and positively associated with visceral fat mass and all
      cause and cardiovascular disease (CVD) in the general population. It is, however,
      uncertain whether ABSI could be associated with arterial stiffness in patients
      with diabetes. METHODS: This is a cross-sectional study of 607 patients with type
      2 diabetes (mean age 64+/-12 years; 40.0% female). Visceral fat area (VFA, cm(2))
      and subcutaneous fat area (SFA, cm(2)) were assessed with a dual-impedance
      analyzer. In order to estimate the risk for CVD, brachial-ankle pulse wave
      velocity (baPWV, cm) was used for the assessment of arterial stiffness. RESULTS:
      ABSI was significantly and positively correlated with VFA (r=0.138, p=0.001) and
      negatively associated with BMI (r=-0.085, p=0.037). The correlation of z-score
      for ABSI with VFA remained significant (r=0.170, p<0.001) but not with BMI
      (r=0.009, p=0.820). ABSI (standardized beta 0.095, p=0.043) but not WC
      (standardized beta -0.060, p=0.200) was significantly and positively correlated
      with baPWV in the multivariate model including BMI as a covariate. CONCLUSIONS:
      ABSI appears to reflect visceral adiposity independently of BMI and to be a
      substantial marker of arterial stiffening in patients with type 2 diabetes.

PMID- 27026811
TI  - Maternal autoantibody profiles at risk for autoimmune congenital heart block: a
      prospective study in high-risk patients.
AB  - OBJECTIVE: This prospective study aimed to identify antibody profiles
      characterising mothers with fetuses developing congenital heart block (CHB) by
      comparing their antibody frequencies and levels with those in unaffected mothers.
      METHODS: Eighty-one consecutive pregnant patients positive to anti-Ro+/-anti-La
      antibodies, at high risk of developing fetal CHB were prospectively studied. The
      16 patients with fetal CHB outcome were considered the study population and the
      65 patients with normal pregnancy outcomes were considered the control cohort.
      Anti-Ro52, anti-Ro60, anti-p200 and anti-La antibodies were assayed using home
      made ELISA assays. RESULTS: The prevalence of anti-p200 antibodies was
      significantly higher in the fetal CHB affected patients than in the controls
      (p=0.03). Combinations of anti-p200 with anti-Ro52 and anti-Ro60 antibodies were
      significantly more frequent in the women with fetuses developing CHB than in the
      controls (p=0.03 for all combinations). The women with fetal CHB had
      significantly higher mean anti-Ro52, anti-Ro60 and anti-p200 levels than the
      controls (p=0.003, p=0.0001 and p=0.04, respectively); mean anti-La/SSB level was
      not significantly different in the two cohorts (p=0.25). CONCLUSIONS: Since anti
      p200, anti-Ro52 and anti-Ro60 antibodies, especially at high level, seem to
      identify patients at increased risk of developing fetal CHB, their detection
      could recognise anti-Ro/La positive women at risk for having an infant with this
      rare, potentially dangerous disorder.

PMID- 27026810
TI  - Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A
      Biracial Cohort (POP-ABC) study.
AB  - BACKGROUND: Adiponectin levels display ethnic disparities, and are inversely
      associated with the risk of type 2 diabetes (T2DM). However, the association of
      adiponectin with prediabetes risk in diverse populations has not been well
      studied. Here, we assessed baseline adiponectin levels in relation to incident
      prediabetes in a longitudinal biracial cohort. RESEARCH DESIGN AND METHODS: The
      Pathobiology of Prediabetes in A Biracial Cohort study followed non-diabetic
      offspring of parents with T2DM for the occurrence of prediabetes, defined as
      impaired fasting glucose and/or impaired glucose tolerance. Assessments at
      enrollment and during follow-up included a 75 g oral glucose tolerance test,
      anthropometry, biochemistries (including fasting insulin and adiponectin levels),
      insulin sensitivity and insulin secretion. Logistic regression was used to
      evaluate the contribution of adiponectin to risk of progression to prediabetes.
      RESULTS: Among the 333 study participants (mean (SD) age 44.2 (10.6) year),
      151(45.3%) were white and 182 (54.8%) were black. During approximately 5.5 (mean
      2.62) years of follow-up, 110 participants (33%) progressed to prediabetes
      (N=100) or T2DM (N=10), and 223 participants (67%) were non-progressors. The mean
      cohort adiponectin level was 9.41+5.30 MUg/mL (range 3.1-45.8 MUg/mL); values
      were higher in women than men (10.3+5.67 MUg/mL vs 7.27+3.41 MUg/mL, p<0.0001)
      and in white than black offspring (10.7+5.44 MUg/mL vs 8.34+4.95 MUg/mL,
      p<0.0001). Adiponectin levels correlated inversely with adiposity and glycemia,
      and positively with insulin sensitivity and high-density lipoprotein cholesterol
      levels. Baseline adiponectin strongly predicted incident prediabetes: the HR for
      prediabetes per 1 SD (approximately 5 MUg/mL) higher baseline adiponectin was
      0.48 (95% CI 0.27 to 0.86, p=0.013). CONCLUSIONS: Among healthy white and black
      adults with parental history of T2DM, adiponectin level is a powerful risk marker
      of incident prediabetes. Thus, the well-known association of adiponectin with
      diabetes risk is evident at a much earlier stage in pathogenesis, during
      transition from normoglycemia to prediabetes.

PMID- 27026812
TI  - Development and validation of a simple lupus severity index using ACR criteria
      for classification of SLE.
AB  - OBJECTIVE: To develop a simple systemic lupus erythematosus (SLE) severity index
      that requires knowledge of only American College of Rheumatology (ACR) criteria
      and subcriteria. METHODS: This study used demographic, mortality and medical
      records data of 1915 patients with lupus from the Lupus Family Registry and
      Repository. The data were randomly split (2:1 ratio) into independent training
      and validation sets. A logistic regression with ridge penalty was used to model
      the probability of being prescribed major immunosuppressive drugs-a surrogate
      indicator of lupus severity. ACR criteria and subcriteria were used as predictor
      variables in this model, and the resulting regression coefficient estimates
      obtained from the training data were used as item weightings to construct the
      severity index. RESULTS: The resulting index was tested on the independent
      validation dataset and was found to have high predictive accuracy for
      immunosuppressive use and early mortality. The index was also found to be
      strongly correlated with a previously existing severity score for lupus. In
      addition, demographic factors known to influence lupus severity (eg, age of
      onset, gender and ethnicity) all showed robust associations with our severity
      index that were consistent with observed clinical trends. CONCLUSIONS: This new
      index can be easily computed using ACR criteria, which may be among the most
      readily available data elements from patient medical records. This tool may be
      useful in lupus research, especially large dataset analyses to stratify patients
      by disease severity, an important prognostic indicator in SLE.

PMID- 27026813
TI  - Non-articular sources of groin pain in the athlete.

PMID- 27026814
TI  - Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid
      injection in the hip.
AB  - The primary purpose of this review article is to discuss the role of diagnostic,
      corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the
      treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These
      treatments play an important biological role in the non-operative management of
      these conditions. Two independent reviewers performed an search of PubMed for
      articles that contained at least one of the following search terms pertaining to
      intra-articular hip injection-local anaesthetic, diagnostic, ultrasound,
      fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI.
      Seventy-two full text articles were suitable for inclusion. There were 18
      articles addressing the efficacy of diagnostic intra-articular hip injections.
      With respect to efficacy in OA there were 25 articles pertaining to efficacy of
      corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the
      efficacy of biologics in FAI. Diagnostic intra-articular hip injections are
      sensitive and specific for differentiating between intra-articular, extra
      articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves
      the precision of intra-articular positioning of diagnostic injections.
      Corticosteroids are more effective than HA and PRP in alleviating pain from hip
      OA. A higher dose of corticosteroids produces a longer benefit but volume of
      injection has no significant effect. Intra-articular corticosteroids do not
      increase infection rates of subsequent arthroplasty. There is currently limited
      evidence to warrant the routine use of therapeutic injections in the management
      of labral tears and FIA. 

PMID- 27026815
TI  - Tissue engineering and the future of hip cartilage, labrum and ligamentum teres.
AB  - As the field of hip arthroscopy continues to evolve, the biological understanding
      of orthopaedic tissues, namely articular cartilage, labral fibro-cartilage and
      the ligamentum teres continues to expand. Similarly, the need for biological
      solutions for the pre-arthritic and early arthritic hip continues to be a
      challenge for the sports medicine surgeon and hip arthroscopist. This article
      outlines existing biological and tissue-engineering technologies, some being used
      in clinical practice and other technologies being developed, and how these
      biological and tissue-engineering principals may one day influence the practice
      of hip arthroscopy. This review of hip literature is specific to emerging
      biological technologies for the treatment of chondral defects, labral tears and
      ligamentum teres deficiency. Of note, not all of the technologies described in
      this article have been approved by the United States Food and Drug Administration
      and some of the described uses of the approved technologies should be considered
      'off-label' uses. 

PMID- 27026816
TI  - Cartilage restoration technique of the hip.
AB  - Hip cartilage lesions represent a diagnostic challenge and can be an elusive
      source of pain. Treatment may present difficulties due to localization and
      spherical form of the joint and is most commonly limited to excision,
      debridement, thermal chondroplasty and microfractures. This chapter will focus in
      new technologies to enhance the standard techniques. These new technologies are
      based in stem cells therapies; as intra-articular injections of expanded
      mesenchymal stem cells, mononuclear concentrate in a platelet-rich plasma matrix
      and expanded mesenchymal stem cells seeded in a collagen membrane. This review
      will discuss the bases, techniques and preliminary results obtained with the use
      of stem cells for the treatment of hip cartilage lesions. 

PMID- 27026817
TI  - Hip arthroscopy in obese, a successful combination?
AB  - Discussion persists about the outcome and results of hip arthroscopy in obese
      patients. Hip arthroscopy gained popularity over time. A current discussion is if
      obese patients can reach similar results after surgery compared with non-obese.
      To our knowledge, this is the first systematic review of literature about hip
      arthroscopy and obesity. We searched the Pubmed/Medline databases for literature
      and included three studies that compared the outcome of hip arthroscopy between
      different BMI groups. We extracted and pooled the data. For continues data a
      weighted mean difference was calculated, for dichotomous variables a weighted
      odds ratio (OR) was calculated using Review Software Manager. Heterogeneity of
      the included studies was calculated using I(2) statistics. Data were extracted
      from two studies. In the Obese group, there was significant more conversion to
      total hip replacement or resurfacing hip replacement (OR = 2.21, 95% CI 1.07
      4.56) and more re-arthroscopy (OR = 4.68, 95% CI 1.41-15.45). Any reoperation
      occurred more often in the obese group (OR = 2.87, 95% CI 1.53-5.38). In the Non
      Arthritic Hip Score obese scored lower than the non-Obese group [10.9 (-14,6 to
      7.1)]. For the modified Harris Hip Score the score is - 6,6, according to the
      MCID this difference is clinically relevant. For both scores obese show lower
      outcomes but similar improvement after hip arthroscopy. Regarding a higher chance
      of needing a re-operation and lower subjective outcome scores obesity appears to
      have a negative influence on the outcome of hip arthroscopy. 

PMID- 27026818
TI  - Adhesive capsulitis of the hip: a review addressing diagnosis, treatment and
      outcomes.
AB  - Adhesive capsulitis (AC) of the hip (i.e. 'Frozen Hip'), in part due to its
      difficulty in diagnosis, is an often overlooked and underappreciated entity of
      hip morbidity. This review aimed to elucidate a diagnostic approach and the
      surgical treatment options (with associated outcomes) of employing hip
      arthroscopy in the setting of AC. Electronic databases (EMBASE, MEDLINE and
      PubMed) were searched for available sources for all relevant clinical studies
      addressing the surgical management of AC. Additionally, reference lists of
      studies were hand-searched to find all relevant articles. Articles were
      systematically screened in duplicate, with agreement and descriptive statistics
      presented. Ten studies satisfied inclusion criteria. A total of 40 patients (mean
      age of 47.1 +/- 14.8 years) were included. Diagnosis of AC of the hip commonly
      encompassed a combination of: decreased joint capacity; hip pain exacerbated by
      weight bearing or activity; and progressive decrease in global range of motion.
      Diagnostic arthroscopy was utilized in nine patients, and successful diagnosis of
      AC was achieved in all nine patients. Common treatments included pressure
      dilation (11 cases) and manipulation under anesthesia (11 cases). AC continues to
      be a difficult clinical entity to diagnose. Similarities are seen between hip AC
      and shoulder AC as diagnosis is often a result of ruling out all other possible
      conditions, and treatment options and outcomes resemble those of the shoulder
      counterpart. With successful outcomes harping on timely diagnosis and effective
      treatment, the use of hip arthroscopy may be of benefit to achieving this. 

PMID- 27026819
TI  - Avulsion of the direct head of rectus femoris following arthroscopic subspine
      impingement resection: a case report.
AB  - Arthroscopic resection of the anterior inferior iliac spine (AIIS) for subspine
      impingement has become a relatively common procedure. The AIIS is the origin of
      the direct head of rectus femoris (dhRF). Previous studies have reported that
      removal of the contributing portion of the AIIS causing impingement is unlikely
      to weaken the attachment of the dhRF. The purpose of this article is to report a
      case of avulsion of the dhRF, following revision hip arthroscopy for the
      treatment of subspine impingement. A 23-year-old professional footballer
      underwent revision left hip arthroscopy for the treatment of subspine
      impingement. 5-mm of bone was resected inferior to the AIIS. Two-weeks post
      operatively, he presented with sudden onset, severe left anterior thigh pain
      following a fall and hyperextension of his left hip. The patient felt a pop over
      the anterior aspect of his hip. He noticed immediate swelling, severe pain and
      stiffness. Examination revealed diffuse swelling, 4/5-power on straight-leg
      raise, focal tenderness over the AIIS but no palpable gap. MRI confirmed the
      clinical suspicion of a dhRF avulsion. Given the minimal loss of power and the
      lack of significant retraction, the patient was treated conservatively. He was
      instructed to avoid excessive hip extension. He returned to full participation at
      3-months. This article highlights a case of avulsion of the dhRF due to a
      hyperextension injury of the hip following arthroscopic resection of subspinal
      impingement, a previously unreported complication. Resection of soft and bone
      from the AIIS may weaken the insertion of the dhRF. Care should be taken during
      post-operative rehabilitation to avoid trauma and excessive forces on the dhRF
      tendon, which may lead to rupture. Rehabilitation should be focused on range of
      motion of the hip. 

PMID- 27026820
TI  - Outcome of hip arthroscopy in patients with mild to moderate osteoarthritis-A
      prospective study.
AB  - Osteoarthritis (OA) of the hip is a common cause of hip pain. The arthroscopic
      management of patients with femoro-acetabular impingement (FAI) has been reported
      to yield good outcomes. The purpose of this study was to report on outcome
      following the arthroscopic treatment of patients with FAI in the presence of mild
      to moderate OA. Seventy-five patients undergoing arthroscopic surgery for FAI,
      all with preoperative radiological signs of mild to moderate OA were
      prospectively included in this study. A 2-year follow-up, using web-based patient
      reported outcome measures, including the International Hip Outcome Tool (iHOT
      12), Copenhagen Hip and Groin Outcome (HAGOS), EQ-5D, Hip Sports Activity Scale
      (HSAS) for physical activity level and a visual analogue scale (VAS) for overall
      hip function, was performed, complemented by a radiographic evaluation. At follow
      up (mean 26 months, SD 5), five patients (7%) had undergone total hip
      arthroplasty, leaving 70 patients for the analysis. Preoperative scores compared
      with those obtained at the 2-year follow-up revealed significant improvements (P
      < 0.0001) for all measured outcomes; the iHOT-12 (42 versus 65), VAS for global
      hip function (48 versus 68), HSAS (2.5 versus 3), EQ5D index (0.62 versus 0.76),
      EQ VAS (69 versus 75) and different HAGOS subscales (54 versus 72, 47 versus 67,
      56 versus 75, 40 versus 61, 33 versus 56, 31 versus 55). At follow-up, 56 (82%)
      patients reported that they was satisfied with the outcome of surgery.
      Arthroscopic treatment for patients with FAI in the presence of mild to moderate
      OA resulted in statistically significant and clinically relevant improvements in
      outcome measures related to pain, symptoms, function, physical activity level and
      quality of life in the majority of patients. 

PMID- 27026821
TI  - Education: the key to successful hip preservation.

PMID- 27026823
TI  - Hip arthroscopy in the warrior athlete: 2 to 10 year outcomes.
AB  - Hip disorders are increasingly recognized among athletic populations. The rigors
      of military service expose individuals to the same risks as those participating
      in competitive sports, compounded by potential exposure to violent macrotrauma.
      This is a retrospective review of prospectively collected data among 62 active
      duty military personnel (64 hips) with 2-10-year follow-up. Follow-up averaged 47
      months (range 24-120 months). The average age was 30 years (range 17-53 years)
      with 45 males and 17 females; 37 right and 27 left hips. Duration of symptoms
      prior to arthroscopy averaged 28 months (range 6-168 months). The average
      improvement was 22 points (pre-op 63; post-op 85) using the 100-point modified
      Harris hip score and was statistically significant (P <  0.001). Patients were
      improved after 60 of 64 procedures (94%) and returned to active duty following 52
      (80%) and an average of 5 months (range 1 week-15 months). Forty-six (72%)
      underwent correction of FAI including 27 combined, 17 cam and two pincer lesions.
      Overall diagnoses and procedures are detailed. One patient underwent repeat
      arthroscopy and remained improved at 2-year follow-up; none were converted to
      total hip arthroplasty. There were two minor complications, a transient ulnar
      nerve neurapraxia and superficial sensory dysesthesias of the foot, both of which
      resolved within a few days. This is a heterogeneous cohort of pathology, but
      illustrates that hip disorders may exist among active duty military personnel and
      may benefit from arthroscopic intervention. A sense of awareness is important for
      accurate diagnosis and timely treatment. 

PMID- 27026822
TI  - Sportsman's hernia? An ambiguous term.
AB  - Groin pain is common in athletes. Yet, there is disagreement on aetiology,
      pathomechanics and terminology. A plethora of terms have been employed to explain
      inguinal-related groin pain in athletes. Recently, at the British Hernia Society
      in Manchester 2012, a consensus was reached to use the term inguinal disruption
      based on the pathophysiology while lately the Doha agreement in 2014 defined it
      as inguinal-related groin pain, a clinically based taxonomy. This review article
      emphasizes the anatomy, pathogenesis, standard clinical assessment and imaging,
      and highlights the treatment options for inguinal disruption. 

PMID- 27026824
TI  - Validation of neck axis distance as a radiographic measure for acetabular
      anteversion.
AB  - Excessive acetabular anteversion is an important treatment consideration in hip
      preservation surgery. There is currently no reliable quantitative method for
      determining acetabular anteversion utilizing radiographs alone. The three main
      purposes of this study were to: (i) define and validate the neck axis distance
      (NAD) as a new visual and reproducible semi-quantitative radiographic parameter
      used to measure acetabular anteversion; (ii) determine the degree of correlation
      between NAD and computed tomography (CT)-measured acetabular anteversion; (iii)
      establish a sensitive and specific threshold value for NAD to identify excessive
      acetabular anteversion. This retrospective cohort study included all patients
      presenting to a single institution over a 14-month period who had undergone a
      dedicated musculoskeletal CT pelvis along with a standardized anteroposterior
      (AP) pelvis radiograph. Trained observers measured the NAD on the AP pelvis
      radiograph and equatorial acetabular anteversion on CT for all hips. Mixed model
      analysis was used to find prediction equations, and ROC analysis was used to
      evaluate the diagnostic accuracy of NAD. NAD is a valid semi-quantitative
      predictor of acetabular anteversion and strongly correlates with CT-measured
      equatorial acetabular anteversion (P  <  0.0001). A NAD measurement of greater
      than 14 mm predicts excessive acetabular anteversion with 76% sensitivity and 78%
      specificity. NAD is an accurate radiographic predictor of acetabular anteversion,
      which may be readily used as an effective screening tool during the evaluation of
      patients with hip pain. 

PMID- 27026825
TI  - What the Papers Say.

PMID- 27026826
TI  - Research trends in biomimetic medical materials for tissue engineering:
      commentary.
AB  - We introduce our active experts' communications and reviews (Part II) of 2015
      Korea-China Joint Symposium on Biomimetic Medical Materials in Republic of Korea,
      which reflect their perspectives on current research trends of biomimetic medical
      materials for tissue regeneration in both Korea and China. The communications
      covered three topics of biomimetics, i.e., 1) hydrogel for therapeutics and
      extracellular matrix environments, 2) design of electrical polymers for
      communications between electrical sources and biological systems and 3) design of
      biomaterials for nerve tissue engineering. The reviews in the Part II will cover
      biomimetics of 3D bioprinting materials, surface modifications, nano/micro
      technology as well as clinical aspects of biomaterials for cartilage. 

PMID- 27026827
TI  - Occasional cooperative breeding in birds and the robustness of comparative
      analyses concerning the evolution of cooperative breeding.
AB  - Cooperative breeding is a widespread and intense form of cooperation, in which
      individuals help raise offspring that are not their own. This behaviour is
      particularly well studied in birds, using both long-term and comparative studies
      that have provided insights into the evolution of reproductive altruism. In most
      cooperatively breeding species, helpers are offspring that remain with their
      parents beyond independency and help in the raising of younger siblings. However,
      many cooperatively breeding species are poorly studied, and in 152 species, this
      behaviour only has been observed infrequently (i.e., occasional cooperative
      breeding). Here we argue that the parental care mode of these 152 species needs
      to be treated with caution, as factors associated with occasional cooperative
      breeding may differ from those associated with "regular" cooperative breeding. In
      most cooperatively breeding species, helpers provide alloparental care at the
      nests of their parents or close relatives; however, only in one occasionally
      cooperatively breeding species do offspring remain into the next breeding season
      with their parents. Accordingly, different factors are likely to be associated
      with regular and occasional cooperative breeding. The latter behaviour resembles
      interspecific feeding (i.e., individuals feed offspring of another species),
      which occurs when birds lose their brood and begin feeding at a nearby nest, or
      when birds mistakenly feed at another nest. Thus, we advise researchers to
      exclude occasional cooperative breeders in comparative analyses until their
      status is clarified, or to categorize them separately or according to the
      typically observed parental care mode. This approach will increase the robustness
      of comparative analyses and thereby improve our understanding of factors that
      drive the evolution of cooperative breeding. 

PMID- 27026829
TI  - Childhood adversity interacts with adult stressful events to predict reduced
      likelihood of smoking cessation among women but not men.
AB  - Research has documented important sex differences in associations between early
      stress, stress-sensitization, and psychiatric outcomes. The current study
      investigated whether sex differences in stress-sensitization extended to
      cigarette smoking cessation. Data were analyzed from the National Epidemiologic
      Survey on Alcohol and Related Conditions (waves 1 and 2), selecting for current
      daily and non-daily smokers at wave 1 (daily smokers: n=3,499 women, 3055 men;
      non-daily smokers: n=451 women, 501 men). Three-way interactions between sex,
      childhood adversity, and past year stressful life events were modeled in the
      prediction of smoking cessation. Among women, stressful life events were more
      strongly related to lower likelihood of smoking cessation for those with a
      history of childhood adversity than those without. This relationship was not
      found among men. The stress-sensitization model may be applicable to women with
      regards to smoking cessation, supporting further exploration of stress
      sensitization as a prevention and clinical target for smoking cessation.

PMID- 27026828
TI  - Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise
      Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot
      Study.
AB  - Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to
      decrease sympathetic nervous system (SNS) activity and inhibit sympathetically
      maintained pain, but its effects on exercise responses have not been reported.
      Methods. Using a randomized double-blind crossover design, we assessed the effect
      of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective
      responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate
      (HR), and ratings of perceived exertion (RPE) during exercise and ratings of
      pain, physical fatigue, and mental fatigue before, during, and for 48 hours after
      exercise were compared in patients on pregabalin versus placebo and also versus
      18 healthy controls. Results. On placebo, exercise RPE and BP were significantly
      higher in FM patients than controls (p < 0.04). Pregabalin responders (n = 12,
      defined by patient satisfaction and symptom changes) had significantly lower
      exercise BP, HR, and RPE on pregabalin versus placebo (p < 0.03) and no longer
      differed from controls (p > 0.26). Cardiovascular responses of nonresponders (n =
      7) were not altered by pregabalin. In responders, pregabalin improved ratings of
      fatigue and pain (p < 0.04), but negative effects on pain and fatigue were seen
      in nonresponders. Conclusions. These preliminary findings suggest that pregabalin
      may normalize cardiovascular and subjective responses to exercise in many FM
      patients. 

PMID- 27026830
TI  - Evaluation of Different Phenotypic Techniques for the Detection of Slime Produced
      by Bacteria Isolated from Clinical Specimens.
AB  - INTRODUCTION : Microorganisms use various strategies for their survival in both
      the environment and in humans. Slime production by bacteria is one such mechanism
      by which microbes colonize on the indwelling prosthetic devices and form
      biofilms. Infections caused by such microorganisms are difficult to treat as the
      biofilm acts as a shield and protects microbes against antimicrobial agents.
      There are several methods for the detection of slime produced by bacteria, and
      they include both phenotypic and molecular methods. The present study evaluated
      the Congo red agar/broth method, Christensen's method, dye elution technique, and
      the latex agglutination method for the demonstration of slime production by
      different bacterial clinical isolates. MATERIALS & METHODS: We collected 151
      bacterial clinical isolates (both gram-positive and gram-negative bacteria) from
      various specimens and tested them for the production of slime both by qualitative
      and quantitative tests. Congo red agar/broth method, Christensen's method, dye
      elution technique, and latex agglutination methods were used for detecting the
      slime or slime-like substance. RESULTS : We found that 103 (68.2%) strains were
      positive for slime production by Congo red agar/broth method. It was found that
      18 (94.7%) strains of Klebsiella pneumoniae, 21 (84.0%) strains of S aureus and
      25 (65.7%) strains of coagulase-negative Staphylococci were positive for slime or
      slime-like substances by Congo red agar/broth method. A total of 41.0% of the
      strains positive by Christensen's method and 15.2% of the strains by dye elution
      technique were found to be more adherent organisms and that have the potential to
      form biofilms. Only the gram-positive organisms showed nonspecific agglutination
      with latex suspension. CONCLUSION : Among the various phenotypic methods compared
      in this study the Congo red agar/broth method is a simple, economical, sensitive,
      and specific method that can be used by clinical microbiology laboratories for
      screening the strains for the presence of slime or slime-like substances.

PMID- 27026831
TI  - Use of Closed Incision Management with Negative Pressure Therapy for Complex
      Cardiac Patients.
AB  - BACKGROUND: In patients with major comorbidities undergoing complex
      cardiothoracic surgery, incision management is critical. This retrospective
      review evaluated negative pressure over closed sternal incisions in cardiac
      patients with multiple comorbidities within 30 days post-median sternotomy.
      METHODS: Records of post-sternotomy patients treated with PrevenaTM Incision
      Management System (KCI, an Acelity company, San Antonio, TX), a closed incision
      negative pressure therapy (ciNPT), were reviewed from September 2010 through
      September 2014. Data collected included demographics, major comorbidities, types
      of surgery, relevant medical history, incision length, therapy duration, time to
      follow-up, and incision complications. Descriptive statistics were computed for
      continuous variables, frequency, and percentages for categorical variables.
      RESULTS: Twenty-seven patients were treated with ciNPT between September 2010 and
      September 2014. The mean patient age was 62.5 (SD 7.9), and the mean body mass
      index (BMI) was 38.5 (SD 4.4) kg/m(2). Risk factors included obesity (BMI >= 30
      kg/m(2), 27/27; 100%), diabetes (25/27; 92.6%), hypertension (16/27; 59.3%), and
      20/27 patients (74%) had >= 5 comorbidities. Mean ciNPT duration was 5.6 (SD 0.9)
      days. Within 30 days post-surgery, 21/27 (77.8%) patients had intact incisions
      with good reapproximation. Two patients experienced minor dehiscences; four cases
      of superficial cellulitis were treated and resolved. One patient with a
      dehiscence was readmitted for intravenous antibiotics and five patients were
      managed successfully with antibiotics as outpatients. All patients had intact
      incisions with good skin approximation at final follow-up. CONCLUSIONS: In this
      retrospective study of post-sternotomy patients at high risk of developing
      complications, ciNPT over closed sternal incisions resulted in favorable outcomes
      within 30 days of surgery.

PMID- 27026832
TI  - Minimally Invasive 2D Navigation-Assisted Treatment of Thoracolumbar Spinal
      Fractures in East Africa: A Case Report.
AB  - Spinal surgery under Eastern-African circumstances is technically demanding and
      associated with significant complications, such as blood loss, infection, and
      wound breakdown. We report a spinal trauma case that was performed using
      minimally invasive surgery (MIS) and navigation, and hypothesize that these newer
      techniques may enable surgeons to perform effective spinal surgery with minimal
      complications and good outcomes.  During the 2014 First Hands-on Neurotrauma
      Course held in Dar es Salaam, Tanzania, we successfully performed three minimally
      invasive and two-dimensional (2D) navigated spinal surgeries to decompress and
      stabilize patients with complete and incomplete spinal injuries. In this report,
      we present a case of a paraplegic patient with a T12 burst fracture who tolerated
      MIS surgery with no intraoperative complications, and is doing well with no
      postoperative complications one year after surgery. Minimally invasive spinal
      surgery and 2D navigation may offer advantages in resource-poor countries. As
      part of the Weill Cornell Tanzania Neurosurgery project and in conjunction with
      the Foundation for International Education in Neurological Surgery (as well as
      other organizations), further experiences with 2D navigation and MIS surgery will
      be recorded in 2015. A neurotrauma registry has already been implemented to
      better understand the current management of neurotrauma in Eastern Africa. 

PMID- 27026833
TI  - Replication Study of Polymorphisms Associated With Brain Arteriovenous
      Malformation in a Population From South of Brazil.
AB  - INTRODUCTION: The aim of this study was to reproducibly determine if any of the
      polymorphisms were associated with the susceptibility to brain arteriovenous
      malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation.
      METHODS: We recruited 63 BAVM patients and 96 controls. The polymorphisms
      selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha
      (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B 
      31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219),
      endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795).
      RESULTS: In the single analysis, we observed statistically significant
      differences in the allele distributions for IL1B -31T>C (rs1143627) between the
      BAVM patients and control subjects (P = 0.02). There was a trend toward
      significance for the association between the IL1B 511C>T (rs16944) allele and
      BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism
      was significantly associated with the risk of BAVM. No polymorphisms were
      associated with hemorrhage presentation according to both single and
      multivariable analyses. CONCLUSIONS: In our sample from a south Brazil
      population, we found no association between the risks of BAVM and ICH
      presentation with any of the selected polymorphisms.

PMID- 27026834
TI  - May-Thurner Syndrome With Pulmonary Embolism as the First Presentation Rather
      Than Deep Vein Thrombosis.
AB  - May-Thurner syndrome (MTS) is a rare disease that causes deep vein thrombosis
      (DVT) in young females (age 20 to 50). DVT is caused by mechanical obstruction of
      the left common iliac vein by the right common iliac artery resulting in stasis
      rather than a primary hypercoagulable state. Although MTS is found in 22% of
      cadavers, it causes <5% of lower extremity venous disorder. Greater than 70%
      compression is needed to cause DVT. MTS patients usually present with acute left
      leg edema. Many cases are recurrent with a past workup negative for other
      etiologies of DVT or pulmonary embolism (PE). Cases rarely present as PE rather
      than DVT. We present a case of this syndrome at a younger-than-typical age with
      PE as the first presentation. Femoral stick venogram is the gold standard for
      diagnosing MTS as therapeutic procedures can be done concurrently.
      Anticoagulation therapy alone is insufficient to prevent recurrence. 

PMID- 27026835
TI  - Recurrent Craniocervical Pseudogout: Indications for Surgical Resection,
      Surveillance Imaging, and Craniocervical Fixation.
AB  - BACKGROUND: Calcium pyrophosphate dihydrate (CPPD) crystallization is known to
      occur in the spine, leading to the development of visible calcification as seen
      by imaging. Occasionally, the deposition of this material can lead to larger
      accumulations that are seen as masses in the articular processes, intervertebral
      discs, and posterior longitudinal ligaments. A particularly significant
      manifestation of this process is at the craniocervical junction, where
      symptomatic presentations can arise. CLINICAL PRESENTATION:  A 74-year-old woman
      presented after several falls from standing, complaining of leg and arm weakness.
      Imaging revealed a mass arising from the C1-C2 articulation dorsal to the dens,
      extending to the clivus. The mass compressed the medulla and cervicomedullary
      junction. INTERVENTION: The patient underwent a left, far lateral craniotomy with
      C1 laminectomy to approach the cervicomedullary junction. The mass was cyst-like
      and contained scattered crystals and amorphous material consistent with
      pseudogout. There were no cells with an elevated Ki-67 index. The patient's
      symptoms and exam improved at follow-up two months later. However, seven months
      after surgery, she declined once again and was found to have a recurrence.
      CONCLUSION: A subtotal resection of pseudogout may lead to recurrence. The
      recurrence can occur in a rapid fashion. Serial MRIs are indicated following
      resection. Occipitocervical fusion could reduce the likelihood of recurrence in
      such cases.

PMID- 27026836
TI  - Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1
      Diabetes Mellitus.
AB  - We present the 15th case reported worldwide and 3rd case reported in Latin
      America of immune thrombocytopenic purpura associated with Type 1 diabetes
      mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed
      ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and
      gastritis due to H. pylori presented to the emergency room with petechiae,
      ecchymosis, and gingival and conjunctival bleeding that had been worsening for
      the past three months. The patient had a body mass index of 18.85 kg/m(2) (P75).
      A biochemical analysis showed 1*10(9) platelets/L, increased prothrombin time,
      increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was
      prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of
      NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid
      every eight hours. The patient's glycemic control was continued with the
      administration of insulin glargine (30 units every 24 hours) and prandial insulin
      glulisine (five to eight units per meal). Before admission, the patient was on a
      prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was
      suspended in the emergency room. For the eradication of H. pylori he was
      prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every
      12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution
      and he was discharged to his home with orders to follow-up with pediatrics,
      hematology, and endocrinology services. The first-line treatment for immune
      thrombocytopenic purpura patients with active bleeding and a platelet count <
      30,000 platelets/MUl is the administration of corticosteroids and inmunoglobulin.

PMID- 27026837
TI  - Concurrent EGFR Mutation and ALK Translocation in Non-Small Cell Lung Cancer.
AB  - Epidermal growth factor receptor (EGFR) mutations and anaplastic large-cell
      lymphoma kinase (ALK) rearrangements are now routine biomarkers that have been
      incorporated into the practice of managing non-small cell lung cancer (NSCLC).
      Historically, the two molecular alterations have been viewed as mutually
      exclusive, but recent identified cases suggest otherwise. In this report, we
      describe cases of lung cancer with concurrent EGFR mutation and ALK rearrangement
      and identify their clinical characteristics. Non-small cell lung cancer patients
      with multiple molecular alterations were retrospectively analyzed from an
      academic referral center from 2011-2013. An additional review was conducted of
      reported cases with dual alterations. Four cases of NSCLC with alterations in
      both EGFR and ALK were identified and evaluated with 16 published cases for a
      total of 20 cases. The age of patients ranged from 37 to 77 years. Nine patients
      were never smokers. The disease control rates in patients treated with EGFR
      inhibitors and ALK inhibitors were 46% (6/13) and 71% (5/7), respectively. This
      series highlights the importance of comprehensive molecular profiling of newly
      diagnosed lung cancer, as NSCLC may be driven by concurrent molecular
      alterations. EGFR- and ALK-targeted therapies appear to have modest activity in
      patients with tumors possessing both alterations. Dual-altered NSCLC patients may
      have distinct clinical characteristics warranting further study. Combination
      targeted therapy or novel multi-targeted tyrosine kinase inhibitors may prove
      important in these patients, though necessary studies remain ongoing. 

PMID- 27026838
TI  - Using Provocative Discography and Computed Tomography to Select Patients with
      Refractory Discogenic Low Back Pain for Lumbar Fusion Surgery.
AB  - Background Context Controversy remains over the use of provocative discography in
      conjunction with computed tomography (CT) to locate symptomatic intervertebral
      discs in patients with chronic, low back pain (LBP). The current study explores
      the relationship between discogenic pain and disc morphology using discography
      and CT, respectively, and investigates the efficacy of this combined method in
      identifying surgical candidates for lumbar fusion by evaluating outcomes. Methods
      43 consecutive patients between 2006 and 2013 who presented with refractory low
      back pain and underwent discography and CT were enrolled in the study. For this
      study, "refractory LBP" was defined as pain symptoms that persisted or worsened
      after 6 months of non-operative treatments. Concordant pain was defined as
      discography-provoked LBP of similar character and location with an intensity of
      >= 8/10. Fusion candidates demonstrated positive-level discography and concordant
      annular tears on CT at no more than two contiguous levels, and at least one
      negative control disc with intact annulus. Surgical outcomes were statistically
      analyzed using Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and
      Short Form-36 (SF-36) for back-related pain and disability preoperatively, and 2
      weeks, 3, 6, 12, and 24 months postoperatively. Results Annular tears were found
      in 87 discs. Concordant pain was reported by 9 (20.9%) patients at L3-L4, 21
      (50.0%) at L4-L5, and 34 (82.9%) at L5-S1; pain occurred significantly more often
      in discs with annular tears than those without (p<0.001). Painless discs were
      independent of annulus status (p=0.90). 18 (42%) of the original 43 patients
      underwent lumbar fusion at L3-L4 (n=1(6%)), L4-L5 (n=6 (33%)), L5-S1 (n=5 (28%)),
      and two-level L4-S1 (n=6 (33%)) via a minimally invasive transforaminal lumbar
      interbody fusion (MITLIF) approach with the aim to replace the nucleus pulposus
      with bone graft material. Median follow-up time was 18 months (range: 12-78
      months). VAS, ODI, and SF-36 scores demonstrated significant improvements at 10
      out of 12 postoperative time points compared with preoperative baseline.
      Conclusions Lumbar discography with post-discography CT can be an effective
      method to evaluate patients with discogenic back pain refractory to non-operative
      treatments. Those patients with one- or two-level high concordant pain scores
      with associated annular tears and negative control disc represent good surgical
      candidates for lumbar interbody spinal fusion. 

PMID- 27026839
TI  - Characterization of silver-kaolinite (AgK): an adsorbent for long-lived (129)I
      species.
AB  - Bentonite is a preferred buffer and backfill material for deep geological
      disposal of high-level nuclear waste (HLW). Bentonite does not retain anions by
      virtue of its negatively charged basal surface. Imparting anion retention ability
      to bentonite is important to enable the expansive clay to retain long-lived
      (129)I (iodine-129; half-life = 16 million years) species that may escape from
      the HLW geological repository. Silver-kaolinite (AgK) material is prepared as an
      additive to improve the iodide retention capacity of bentonite. The AgK is
      prepared by heating kaolinite-silver nitrate mix at 400  degrees C to study the
      kaolinite influence on the transition metal ion when reacting at its
      dehydroxylation temperature. Thermo gravimetric-Evolved Gas Detection analysis, X
      ray diffraction analysis, X-ray photo electron spectroscopy and electron probe
      micro analysis indicated that silver occurs as AgO/Ag2O surface coating on
      thermally reacting kaolinite with silver nitrate at 400  degrees C. 

PMID- 27026840
TI  - Mycoplasma-induced minimally conscious state.
AB  - Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired
      respiratory tract infection and often presents as atypical pneumonia. Following
      airborne infection and a long incubation period, affected patients mostly suffer
      from mild or even asymptomatic and self-limiting disease. In particular in school
      aged children, M. pneumoniae is associated with a wide range of extrapulmonary
      manifestations including central nervous system (CNS) disease. In contrast to
      children, severe CNS manifestations are rarely observed in adults. We report a
      case of a 37 year-old previously healthy immunocompetent adult with fulminant M.
      pneumoniae-induced progressive encephalomyelitis who was initially able to walk
      to the emergency department. A few hours later, she required controlled
      mechanical ventilation for ascending transverse spinal cord syndrome, including
      complete lower extremity paraplegia. Severe M. pneumoniae-induced
      encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and
      immunosuppressive therapy was applied on the intensive care unit. Despite early
      and targeted therapy using four different immunosuppressive strategies, clinical
      success was limited. In our patient, locked-in syndrome developed followed by
      persistent minimally conscious state. The neurological status was unchanged until
      day 230 of follow-up. Our case underlines that severe M. pneumoniae- related
      encephalomyelitis must not only be considered in children, but also in adults.
      Moreover, it can be fulminant and fatal in adults. Our case enhances the debate
      for an optimal antimicrobial agent with activity beyond the blood-brain barrier.
      Furthermore, it may underline the difficulty in clinical decision making
      regarding early antimicrobial treatment in M. pneumoniae disease, which is
      commonly self-limited. 

PMID- 27026841
TI  - Impact of chest wall motion caused by respiration in adjuvant radiotherapy for
      postoperative breast cancer patients.
AB  - To determine the chest wall movement of each patient during deep inspiratory
      breath hold (DIBH) and expiratory breath hold (EBH) in postoperative breast
      cancer patients. Postoperative breast cancer patients who underwent CT simulation
      for 3D radiotherapy treatment planning during December 2012 to November 2013 were
      included. Before scanning the radio-opaque wire was placed on the surface for
      breast and chest wall visualization on CT images, then the patient underwent
      three phases of CT scanning (free breathing, DIBH, and EBH, respectively). The
      distances of chest wall motion at five reference points were calculated using the
      treatment planning system. 38 breast cancer patients who underwent surgery were
      included. Median age was 48.5 (28-85) years. Median BMI was 23.4 (16.6-38.3)
      kg/m(2). Median lung volume was 3160.5 (1830.8-4754.0) cm(3). Median Haller index
      was 2.43 (1.92-3.56). Median chest wall movement was wider in anteroposterior (A
      P, 4.2-5.4 mm) than superoinferior (S-I, 2.5-2.6 mm) and mediolateral (M-L, 0.6
      1.1 mm) dimension in all five measured points. There was no significant effect of
      the type of surgery, BMI, lung volume, and the Haller index on the distances of
      chest wall movement. Additional margins of 7, 5, and 2 mm to the A-P, S-I, and M
      L dimension should adequately cover the extreme chest wall movement in 95 % of
      the patients. This study showed that the maximal movement of the chest wall
      during DIBH and EBH was greatest in the A-P axis followed by the S-I axis, while
      the M-L axis was minimally affected by respiration. 

PMID- 27026842
TI  - Cloning and characterization of filamentous temperature-sensitive protein Z from
      Xanthomonas oryzae pv. Oryzae.
AB  - The ftsZ gene from Xanthomonas oryzae pv. Oryzae was amplified by PCR with the
      specific primers, and the recombinant plasmid pET-22b-ftsZ was constructed
      successfully. The FtsZ with a 6* His tag was overexpressed in a soluble form in
      Escherichia coli BL21 and purified through a Ni-NTA agarose column. The purified
      recombinant FtsZ showed a single band on SDS-PAGE with an apparent molecular mass
      of about 44 kDa, and confirmed by western blotting analysis. The optimum
      temperature for GTPase activity of the recombined FtsZ was 50  degrees C, and the
      optimum pH was 7.0. The recombinant FtsZ showed good stability and retained >95 %
      activity at 50  degrees C for 240 min. The GTPase activity followed Michaelis
      Menten kinetics with the KM of 1.750 mM and the Vmax of 0.155 nmol Pi/min/nmol
      FtsZ respectively. 

PMID- 27026843
TI  - Non-covalent interactions involving halogenated derivatives of capecitabine and
      thymidylate synthase: a computational approach.
AB  - Capecitabine, a fluoropyrimidine prodrug, has been a frequently chosen ligand for
      the last one and half decades to inhibit thymidylate synthase (TYMS) for
      treatment of colorectal cancer. TYMS is a key enzyme for de novo synthesis of
      deoxythymidine monophosphate and subsequent synthesis of DNA. Recent years have
      also seen the trait of modifying ligands using halogens and trifluoromethyl (
      CF3) group to ensure enhanced drug performance. In this study, in silico
      modification of capecitabine with Cl, Br, I atoms and -CF3 group has been
      performed. Density functional theory has been employed to optimize the drug
      molecules and elucidate their thermodynamic and electrical properties such as
      Gibbs free energy, enthalpy, electronic energy, dipole moment and frontier
      orbital features (HOMO-LUMO gap, hardness and softness). Flexible and rigid
      molecular docking have been implemented between drugs and the receptor TYMS. Both
      inter- and intra-molecular non-covalent interactions involving the amino acid
      residues of TYMS and the drug molecules are explored in details. The drugs were
      superimposed on the resolved crystal structure (at 1.9 A) of ZD1694/dUMP/TYMS
      system to shed light on similarity of the binding of capecitabine, and its
      modifiers, to that of ZD1694. Together, these results may provide more insights
      prior to synthesizing halogen-directed derivatives of capecitabine for anticancer
      treatment. 

PMID- 27026844
TI  - Genetic association of PROC variants with pulmonary embolism in Northern Chinese
      Han population.
AB  - To evaluate SNPs (single nucleotide polymorphism) in PROC (protein C gene)
      associated with pulmonary embolism (PE) susceptibility in North Chinese Han
      population. A case-control study design was used, and patients with PE and
      healthy participants were enrolled from the Emerging Department of the several
      hospitals in Weifang, Shandong, China. SNPs in PROC were genotyped using Mass
      ARRAY system. The allele frequency of rs199469469 was significantly different
      between PE patients and the control [OR (95 % CI) = 5.00 (1.66-15.12), P =
      0.004], and the difference remained significantly after controlling for age and
      gender [OR (95 % CI) = 5.34 (1.47-19.39), P = 0.011). The G(del)G in the
      haplotype includes rs1799809|rs199469469|rs2069928 was of a significantly
      difference (P = 0.016) among PE patients and the controls, and remained
      significant (P = 0.015) after adjustment for age and sex. Our study reports that
      PROC SNPs (rs199469469) might be associated with PE susceptibility, with the G
      allele of rs199469469 serving as the protective factors for incidence of PE.
      These findings may contribute to the understanding and primary prevention of PE. 

PMID- 27026845
TI  - Safety enhancement in adult body computed tomography scanning: comparison of
      iodixanol versus iohexol.
AB  - BACKGROUND: The aim of this study was to compare the safety and intra-individual
      contrast enhancement of low-osmolar monomeric iohexol and the iso-osmolar dimeric
      iodixanol in body computed tomography (CT) scanning. METHODS: In this single
      center, double-blind, prospective study, a total of 2000 consecutive patients
      undergoing adult body CT scanning were prospectively enrolled, with 1000 patients
      assigned to iodixanol and 1000 patients assigned to iohexol. In both groups, the
      contrast medium was injected at the rate of 3.5 ml/s. Subjective assessment of
      image quality for each image was determined using a 3-grading scale by three
      reviewers. Patients were monitored with questioning and vital signs before
      injection, immediately after injection, and at 24 and 48 h. Extensive laboratory
      evaluation also was performed. RESULTS: Laboratory results showed no significant
      difference across groups. There were also no detectable differences in image
      quality between the two contrast groups in this study. The total adverse
      reactions occurred in less than 1 % of individuals receiving iodixanol comparing
      to 2.5 % in iohexol group (P < 0.05). Among them, only 0.7 % patients injecting
      iodixanol suffered immediate events, comparing to 2 % patients in iohexol group.
      In all, 0.2 % patients with iodixanol and 0.5 % with iohexol had late allergic
      reaction. Further, No deaths occurred in any of the two groups. CONCLUSIONS: The
      iso-osmolar iodixanol provides image quality compared with that of iohexol, with
      lower incidence of adverse events.

PMID- 27026846
TI  - Does voluntary hypoventilation during exercise impact EMG activity?
AB  - It has been reported that exercise under hypoxic conditions induces reduced
      muscle oxygenation, which could be related to enhanced activity on
      electromyography (EMG). Although it has been demonstrated that exercise under
      conditions of voluntary hypoventilation (VH) evokes muscle deoxygenation, it is
      unclear whether VH during exercise impacts EMG. Seven men performed bicycle
      exercise for 5 min at 65 % of peak oxygen uptake with normal breathing (NB) and
      VH. Muscle oxygenation; concentration changes in oxyhemoglobin (Oxy-Hb),
      deoxyhemoglobin (Deoxy-Hb) and total hemoglobin (Total-Hb); and surface EMG in
      the vastus lateralis muscle were simultaneously measured. In the VH condition,
      Oxy-Hb was significantly lower and Deoxy-Hb was significantly higher compared to
      those in the NB condition (P < 0.05 for both), whereas there was no significant
      difference in Total-Hb between the two conditions. We observed significantly
      higher values (P < 0.05) on integrated EMG during exercise under VH conditions
      compared to those under NB conditions. This study suggests that VH during
      exercise augments EMG activity. 

PMID- 27026847
TI  - Cor triatriatum sinister: a rare underlying cause of pulmonary hemosiderosis.
AB  - Pulmonary hemosiderosis is a disorder with unknown cause and characterized by
      hemosiderin appreciation in alveolar interstitium from decomposed hemoglobin
      following alveolar capillary bleeding, which finally leads to pulmonary fibrosis.
      It can be divided into primary and secondary types in terms of its etiology.
      While primary types are related to autoimmunity, secondary types can be
      associated with cardiovascular and pulmonary causes such as mitral stenosis
      leading to pulmonary congestion. We report a case of cor triatriatum sinister in
      a child who presented with hemoptysis as a main clinical manifestation and had
      been previously diagnosed with idiopathic pulmonary hemosiderosis. Based on
      clinical signs and imaging examinations, we considered the hemoptysis was most
      likely due to cor triatriatum. The child underwent corrective surgery with
      uneventful recovery. The hemoptysis has not recurred any more after operation.
      Cardiovascular disease including cor triatriatum should be considered with
      regards to the etiology of pulmonary hemosiderosis. 

PMID- 27026848
TI  - Are the knee and ankle angles at contact related to the tendon properties of
      lower limbs in long distance runners?
AB  - The purpose of this study was to investigate whether the knee and ankle angles at
      contact during running were related to the elastic properties of tendon
      structures in knee extensors and plantar flexors and performance in trained long
      distance runners. Thirty-two highly trained male long distance runners
      participated in this study. Elongation of tendon structures in knee extensors and
      plantar flexors were measured using ultrasonography while subjects performed ramp
      isometric contractions up to the voluntary maximum. The relationship between
      estimated muscle force and tendon elongation was fit to a linear regression, the
      slope of which was defined as the stiffness of tendon structures. Knee and ankle
      angles at contact during running were determined at a speed of 18 km/h on a
      treadmill. Knee and ankle angles at contact were not correlated to the stiffness
      of tendon structures in knee extensors and plantar flexors. In addition, the best
      official record in a 5000-m race was not significantly correlated to knee and
      ankle joint angles at contact. In conclusion, knee and ankle angles at contact
      were not related to the elastic properties of tendon structures in knee extensors
      and plantar flexor and the performance of long distance running. 

PMID- 27026849
TI  - Accuracy of magnetic resonance imaging for predicting pathological complete
      response of breast cancer after neoadjuvant chemotherapy: association with breast
      cancer subtype.
AB  - A pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is a
      signature of favorable prognosis in breast cancer. The aim of this study was to
      assess the accuracy of magnetic resonance imaging (MRI) in predicting the pCR
      after NAC. 265 women with stage II or III breast cancer who underwent surgery
      after NAC were retrospectively investigated for MRI findings before and after the
      NAC. Correlation of pCR with an "imaging complete response" (iCR), defined as no
      detectable tumor on all serial images with dynamic contrast-enhanced T1-weighted
      imaging, was evaluated with respect to each tumor subtype. Of 265 cases, 44 (16.6
      %) and 24 (9.1 %) were diagnosed as iCR and pCR, respectively. Nineteen of the 44
      iCR cases (43.2 %) were assessed as pCR, and 216 (97.7 %) of the 221 non-iCR
      cases were assessed as non-pCR. The accuracy (ACC), the pCR predictive value
      (PPV) and the non-pCR predictive value (NPV) were 88.7, 43.2, and 97.7 %,
      respectively. When assessed according to each tumor subtype, the ACC, PPV and NPV
      were 93.2, 21.4 and 100 % for luminal subtype, 70.8, 0 and 89.5 % for
      luminal/HER2 subtype, 75, 57.1 and 88.8 % for HER2-enriched subtype, and 90.9,
      72.7 and 97 % for triple-negative subtype, respectively. MRI is a valuable
      modality for predicting pCR of breast cancer after NAC treatment. However, its
      accuracy varies greatly in different breast cancer subtypes. Whereas MRI closely
      predicts pCR in the triple-negative subtype, iCR in the luminal subtype is often
      an over-estimation. On the other hand, residual lesions identified by MRI are
      reliable markers of non-pCR for the luminal subtype. 

PMID- 27026850
TI  - Margin evaluation of translational and rotational set-up errors in intensity
      modulated radiotherapy for cervical cancer.
AB  - A clinical target volume (CTV) to planning target volume (PTV) margin recipes was
      routinely used to ensure dose was actually delivered to target for all (most)
      patients. Currently used margin recipes were associated with only translational
      set-up errors in radiotherapy. However, when set-up errors extended to six-degree
      (6D) scope (three translational and three rotational set-up errors), margin
      recipe should be re-evaluated. The purpose of this study was to investigate
      dosimetric changes of targets (both CTV and PTV) coverage when 6D set-up errors
      were introduced and testify the practicability of currently used margin recipe in
      radiotherapy. A total number of 105 cone beam computer tomography scans for ten
      patients with cervical cancer were derived prior to treatment delivery and 6D set
      up errors were acquired with image registration tools. Target coverage was
      evaluated retrospectively for 6D set-up errors introduced plan with 6 mm CTV to
      PTV margin. Target coverage of PTV showed significant decreases (3.3 %) in set-up
      errors introduced plans compared with original plans. But CTV coverage was not
      susceptible to these set-up errors. A tendency of coverage decrease for PTV along
      with distance away from treatment was testified, from -0.2 to -6.2 %. However,
      CTV seems changed less, from -0.2 to -0.8 %. The result indicate that a CTV to
      PTV margin of 6 mm was sufficient to take into account 6D set-up errors for most
      patients with cervical cancer. Future research suggests a smaller margin to
      further improve both tumor coverage and organs at risk sparing. 

PMID- 27026851
TI  - A novel approach to solve nonlinear Fredholm integral equations of the second
      kind.
AB  - In this paper, we present a novel approach to solve nonlinear Fredholm integral
      equations of the second kind. This algorithm is constructed by the integral mean
      value theorem and Newton iteration. Convergence and error analysis of the
      numerical solutions are given. Moreover, Numerical examples show the algorithm is
      very effective and simple. 

PMID- 27026852
TI  - Scientific validation of medicinal plants used by Yakkha community of Chanuwa
      VDC, Dhankuta, Nepal.
AB  - Ethnobotanical knowledge is important among tribal people, but much of the
      information is empirical due to the lack of scientific validation. The purpose of
      this study was to document the medicinal plants used by an ethnic group (Yakkha)
      at Chanuwa VDC of Dhankuta district in Nepal and to validate scientifically in
      the use of plants based on results of phytochemical, antimicrobial and
      antioxidant property analyses and available literature reports. Data were
      collected through interviews of the Yakkha people with the help of a semi
      structured questionnaire and the guided field walk method. A total of 30
      different medicinal plants were recorded along with their vernacular names (for
      few plants) used by the Yakkha community's people. Literature review reveals that
      most of the plant species described herein have also been used in other
      countries, too. Among 30 plants selected for this study methanol extract of five
      ethno-medicinal plants viz., Dendrocnide sinuata, Solanum anguivi, Pogostemon
      cablin, Boehmeria platyphylla and Clerodendrum trichotomum and ethanol extract of
      C. trichotomum were subjected for antibacterial and antioxidant properties. The
      antimicrobial activities were measured using the paper disc diffusion method. The
      antioxidant properties of plants were measured by DPPH and FRAP reduction assay.
      Among all extracts, ethanol extract of C. trichotomum and methanol extract of B.
      platyphylla displayed the highest antibacterial and antioxidant activities,
      respectively. 

PMID- 27026853
TI  - U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving
      Phosphoinositide-specific Phospholipases C.
AB  - The definition of the number and nature of the signal transduction pathways
      involved in the pathogenesis and the identification of the molecules promoting
      metastasis spread might improve the knowledge of the natural history of
      osteosarcoma, also allowing refine the prognosis and opening the way to novel
      therapeutic strategies. Phosphatydil inositol (4,5) bisphosphate (PIP2),
      belonging to the Phosphoinositide (PI) signal transduction pathway, was related
      to the regulation of ezrin, an ezrin-radixin-moesin protein involved in
      metastatic osteosarcoma spread. The levels of PIP2 are regulated by means of the
      PI-specific Phospholipase C (PLC) enzymes. Recent literature data suggested that
      in osteosarcoma the panel of expression of PLC isoforms varies in a complex and
      unclear manner and is related to ezrin, probably networking with Ras GTPases,
      such as RhoA and Rac1. We analyzed the expression and the subcellular
      localization of PLC enzymes in cultured human osteosarcoma MG-63 cells, commonly
      used as an experimental model for human osteoblasts, using U-73122 PLC inhibitor,
      U-73343 inactive analogue, and by silencing ezrin. The treatment with U-73122
      significantly reduces the number of MG-63 viable cells and contemporarily
      modifies the expression and the subcellular localization of selected PLC
      isoforms. U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line
      involving PI-specific Phospholipases C. 

PMID- 27026854
TI  - Hemodynamic changes under balloon occlusion of hepatic artery: predictor of the
      short-term therapeutic effect of balloon-occluded transcatheter arterial
      chemolipiodolization using miriplatin for hepatocellular carcinoma.
AB  - To clarify the hemodynamic changes under balloon occlusion of the hepatic artery
      and to identify predictors of the short-term therapeutic effect (TE) after
      balloon-occluded transcatheter arterial chemoembolization using miriplatin (B
      TACE) for hepatocellular carcinoma (HCC). Tumor variables and angiographic data
      were collected for 35 nodules (29 patients) with a B-TACE for HCC. Lesions were
      classified into three groups based on the balloon-occluded CT hepatic
      arteriography (BO-CTHA) results: Group A, presence of corona enhancement; Group
      B, absence of corona enhancement; Group C, decreased perfusion or perfusion
      defect compared to standard CTHA. Objective response was defined as TE3/4, and
      poor TE as TE1/2, evaluated by response evaluation criteria in cancer of the
      liver at 1-4 months after the procedure. Univariate analysis revealed that
      proximal level of balloon occlusion, intratumoral lower CT values immediately
      after treatment and BO-CTHA findings were significantly correlated with poor TE
      (p = 0.034, 0.037, and 0.003, respectively). Multivariate logistic analysis
      identified the Group C as a significant factor associated with the worse short
      term TE (odds ratio 8.34; 95 % confidence interval 1.49-68.8). Partial or
      complete perfusion defect on BO-CTHA was an independent factor associated with
      poor therapeutic effect. 

PMID- 27026855
TI  - Genotyping of enteroviruses isolated in Kenya from pediatric patients using
      partial VP1 region.
AB  - Enteroviruses (EV) are responsible for a wide range of clinical diseases in
      humans. Though studied broadly in several regions of the world, the genetic
      diversity of human enteroviruses (HEV) circulating in the sub-Saharan Africa
      remains under-documented. In the current study, we molecularly typed 61 HEV
      strains isolated in Kenya between 2008 and 2011 targeting the 3'-end of the VP1
      gene. Viral RNA was extracted from the archived isolates and part of the VP1 gene
      amplified by RT-PCR, followed by sequence analysis. Twenty-two different EV types
      were detected. Majority (72.0 %) of these belonged to Enterovirus B species
      followed by Enterovirus D (21.3 %) and Enterovirus A (6.5 %). The most frequently
      detected types were Enterovirus-D68 (EV-D68), followed by Coxsackievirus B2 (CV
      B2), CV-B1, CV-B4 and CV-B3. Phylogenetic analyses of these viruses revealed that
      Kenyan CV-B1 isolates were segregated among sequences of global CV-B1 strains.
      Conversely, the Kenyan CV-B2, CV-B3, CV-B4 and EV-D68 strains generally grouped
      together with those detected from other countries. Notably, the Kenyan EV-D68
      strains largely clustered with sequences of global strains obtained between 2008
      and 2010 than those circulating in recent years. Overall, our results indicate
      that HEV strains belonging to Enterovirus D and Enterovirus B species pre
      dominantly circulated and played a significant role in pediatric respiratory
      infection in Kenya, during the study period. The Kenyan CV-B1 strains were
      genetically divergent from those circulating in other countries. Phylogenetic
      clustering of Kenyan EV-D68 strains with sequences of global strains circulating
      between 2008 and 2010 than those obtained in recent years suggests a high genomic
      variability associated with the surface protein encoding VP1 gene in these
      enteroviruses. 

PMID- 27026856
TI  - A general theorem on the stability of a class of functional equations including
      quadratic-additive functional equations.
AB  - We prove a general stability theorem of an n-dimensional quadratic-additive type
      functional equation [Formula: see text]by applying the direct method. 

PMID- 27026857
TI  - Production of secretory cutinase by recombinant Saccharomyces cerevisiae
      protoplasts.
AB  - BACKGROUND: During heterologous protein production using recombinant microbes,
      the protein tends to accumulate in the cell and may not be secreted. Here, we
      studied the production of secretory cutinase (heterologous protein) by
      recombinant Saccharomyces cerevisiae protoplasts. FINDINGS: Recombinant S.
      cerevisiae cells (i.e., cells into which the cutinase gene was transferred)
      secreted trace amounts of cutinase into the broth. Approximately 28 % of the
      cutinase produced in the cells localized to the cell walls and/or between cell
      wall and cell membrane (CW). In comparison with cell culture, protoplasts in a
      static culture secreted measurable amounts of cutinase into the broth.
      Protoplasts were protected from physical and osmotic stresses by entrapping them
      in a membrane capsule with a low-viscous liquid-core of 1.92 % w/v calcium
      alginate. To increase secretory cutinase production, the entrapped protoplasts
      were cultivated in a shake flask at low osmotic pressure without disruption.
      During 60 h of cultivation, the extracellular cutinase activity of the free
      protoplasts at 29.3 atm and protoplasts entrapped in the capsule at 17.2 atm were
      0.13 and 0.39 U/mL, respectively. CONCLUSIONS: This is the first report which
      demonstrates that the efficient production of a secretable enzyme by using
      protoplasts isolated from recombinant microbes. This system described here is
      useful to produce products that accumulate in the CW.

PMID- 27026858
TI  - Elevated D-dimer and fibrinogen levels in serum of preoperative bone fracture
      patients.
AB  - The changes of coagulation parameters in preoperative fracture patients reflect
      the coagulation status before surgery. We did retrospective assessment of
      preoperative fracture patients (n = 113) admitted to the hospital between
      September 2013 and September 2014. The control group were selected from healthy
      adults (n = 113) with matched age and gender. Platelet, PT INR, APTT, fibrinogen
      (FIB) and D-dimer values were collected and analyzed. PT INR level was 1.043 +/-
      0.119, APTT was 31.91 +/- 7.56 s, FIB was 320.6 +/- 71.8 mg/dl and D-dimer was
      1283 +/- 1582 ng/ml for the fracture patients. For the control group, PT INR
      level was 0.9976 +/- 0.0602, APTT was 33.22 +/- 2.55 s, FIB was 277.3 +/- 44.7
      mg/dl and D-dimer was 97.53 +/- 63.90 ng/ml. Meanwhile, D-dimer levels of
      different sites of fractures were also measured: Femora 2448 +/- 1961 ng/ml;
      Humerus 792.4 +/- 691.2 ng/ml; Ulna/Radius 619.4 +/- 843.7 ng/ml; Vertebra 647.7
      +/- 787.1 ng/ml; Tibia/Fibula 496.3 +/- 268.8 ng/ml; Clavicle 260.9 +/- 170.9
      ng/ml; Ankle 415.4 +/- 286.6 ng/ml. To conclude, D-dimer and fibrinogen levels
      get higher in preoperative fracture patients than controls. Besides, D-dimer
      levels are significantly different among different locations of fractures, and
      our data revealed that D-dimer levels of Femora fracture were higher than other
      sites. 

PMID- 27026859
TI  - Validity of a food frequency questionnaire to assess nutritional intake among Sri
      Lankan adults.
AB  - Sri Lanka is undergoing nutritional transition and diet-related chronic diseases
      are emerging as an important health problem. Currently, no validated food
      frequency questionnaire (FFQ) exists to measure habitual dietary intake of Sri
      Lankan adults. The purpose of the study is to assess the validity of a semi
      quantitative FFQ and 7-day weighed-intake dietary records (7DWR), designed to
      assess dietary intake among Sri Lankan adults. Dietary intake was measured using
      both a FFQ and 7DWR. The FFQ consisted of 8 food groups containing the main foods
      comprising the diet of Sri Lankan adults, a total of 85 items and 12 color
      photographs to identify serving size. One hundred healthy adults were randomly
      recruited from a community sample and administrated the FFQ followed by
      completion of the 7DWR. Paired sample t tests, Pearson's correlation
      coefficients, kappa test and Bland-Altman analysis were conducted to determine
      correlation and the level of agreement for energy and micronutrients. Seventy
      seven participants completed both the FFQ and 7DWR. Estimated mean energy intake
      (SD) from FFQ (1794 +/- 398 kcal) and 7DWR (1698 +/- 333 kcal, p < 0.001) were
      significantly different due to a significant overestimation of carbohydrate (11.5
      g/day, p < 0.001) and to some extent fat (5.7 g/day, ns). Significant positive
      correlations (p < 0.05) were found between the FFQ and 7DWR for energy (r =
      0.39), carbohydrate (r = 0.47), protein (r = 0.26), fat (r = 0.17) and dietary
      fiber (r = 0.32). Bland-Altman graphs indicated fairly good agreement between
      methods with no relationship between bias and average intake of each nutrient
      examined. Based on these findings, the FFQ appears to be an acceptable tool for
      assessing the nutrient intake of Sri Lankans and will assist proper
      categorization of individuals by dietary intake. 

PMID- 27026860
TI  - Strains of Mycobacterium tuberculosis differ in affinity for human osteoblasts
      and alveolar cells in vitro.
AB  - Although the lung is the primary site of infection of tuberculosis, Mycobacterium
      tuberculosis is capable of causing infection at other sites. In 5-10 % such extra
      pulmonary tuberculosis is located in bone tissue of the spine. It is unknown
      whether host or microbial factors are responsible for the site where extra
      pulmonary tuberculosis manifests itself. One MDR isolate belonging to strain F28,
      one susceptible F11 and one isolate each of susceptible, MDR and XDR F15/LAM4/KZN
      were cultured in Middlebrook 7H9 media. Human osteoblasts (SaOS-2) and human
      alveolar epithelial cells (A549) were exposed to these different isolates of M.
      tuberculosis and invasion capacity and intra-cellular multiplication rates were
      established. Mouse macrophage (MHS) cells exposed to M. tuberculosis H37Rv served
      as control. The invasion capacity of F15/LAM4/KZN representatives increased with
      the level of resistance. The F28 MDR strain showed similar invasion capacity as
      the XDR F15/LAM4/KZN for pulmonary epthelial cells, whilst the fully susceptible
      F11 strain displayed a propensity for osteoblasts. The differences observed may
      in part explain why certain strains are able to cause infection at specific extra
      pulmonary sites. We postulated that the development of extra-pulmonary
      tuberculosis depends on the ability of the microbe to pass effectively through
      the alveolar epithelial lining and its affinity for cells other than those in
      pulmonary tissue. 

PMID- 27026861
TI  - A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy
      for HER2-negative locally advanced or metastatic breast cancer.
AB  - The treatment goals for metastatic breast cancer (MBC) are prolonging survival
      and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor,
      demonstrated improved survival in previous studies and also showed mild toxicity
      when used in late-line therapy for MBC. We conducted a phase II study to
      investigate the efficacy of eribulin mesylate as the first-line chemotherapy for
      human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase
      II, open-label, single-arm, multicenter trial conducted in Japan. Patients with
      HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of
      each 21-day cycle). The primary efficacy outcome was overall response rate (ORR).
      Secondary outcomes included time to treatment failure, progression-free survival
      (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled
      and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and
      clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8
      months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63
      % of patients. The majority of non-hematological adverse events were mild in
      severity. The present trial demonstrated that eribulin has antitumor activity
      comparable with other key established cytotoxic agents with acceptable safety and
      tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for
      patients with HER2-negative MBC. 

PMID- 27026862
TI  - Adaption of the temporal correlation coefficient calculation for temporal
      networks (applied to a real-world pig trade network).
AB  - The average topological overlap of two graphs of two consecutive time steps
      measures the amount of changes in the edge configuration between the two
      snapshots. This value has to be zero if the edge configuration changes completely
      and one if the two consecutive graphs are identical. Current methods depend on
      the number of nodes in the network or on the maximal number of connected nodes in
      the consecutive time steps. In the first case, this methodology breaks down if
      there are nodes with no edges. In the second case, it fails if the maximal number
      of active nodes is larger than the maximal number of connected nodes. In the
      following, an adaption of the calculation of the temporal correlation coefficient
      and of the topological overlap of the graph between two consecutive time steps is
      presented, which shows the expected behaviour mentioned above. The newly proposed
      adaption uses the maximal number of active nodes, i.e. the number of nodes with
      at least one edge, for the calculation of the topological overlap. The three
      methods were compared with the help of vivid example networks to reveal the
      differences between the proposed notations. Furthermore, these three calculation
      methods were applied to a real-world network of animal movements in order to
      detect influences of the network structure on the outcome of the different
      methods. 

PMID- 27026863
TI  - Metabolic inhibition of meloxicam by specific CYP2C9 inhibitors in Cunninghamella
      blakesleeana NCIM 687: in silico and in vitro studies.
AB  - Specific inhibitors of Cytochrome P4502C9 enzyme (CYP2C9) viz. clopidogrel,
      fenofibrate fluvoxamine and sertraline at concentration of 50, 100, 150 and 200
      uM were employed to investigate the nature of enzyme involved in bioconversion of
      meloxicam to its main metabolite 5-OH methyl meloxicam by Cunninghamella
      blakesleeana. Virtual screening for interaction of specific CYP2C9 inhibitors
      with human CYP2C9 enzyme was performed by molecular docking using Auto dock vina
      4.2 version. The in silico studies were further substantiated by in vitro
      studies, which indicated fenofibrate to be a potent inhibitor of CYP2C9 enzyme
      followed by sertraline, clopidogrel and fluvoxamine, respectively. Two-stage
      fermentation protocol was followed to study metabolism of meloxicam and its
      inhibition by different CYP2C9 inhibitors. Meloxicam metabolites were identified
      using HPLC, LC-MS analysis and based on previous reports, as 5-OH methyl
      meloxicam (M1), 5-carboxy meloxicam (M2) and an unidentified metabolite (M3). All
      the inhibitors tested in the study showed a clear concentration dependent
      inhibition of meloxicam metabolism. The results suggest that the enzymes involved
      in metabolism of meloxicam in C. blakesleeana are akin to mammalian metabolism.
      Hence, C. blakesleeana can be used as a model organism in studying drug
      interactions and also in predicting mammalian drug metabolism. 

PMID- 27026864
TI  - The effect of expectation on satisfaction in total knee replacements: a
      systematic review.
AB  - Total knee replacement has reliably been shown to have a beneficial effect in
      knee osteoarthritis; however, around 17 % of patients are dissatisfied with the
      result. A commonly proposed mechanism driving the dissatisfaction rate is a
      discrepancy between expected and actual/perceived outcome. Our aim was to conduct
      a systematic review examining any association between pre-operative expectations
      and satisfaction. A comprehensive electronic search strategy was used to identify
      studies from MEDLINE, EMBASE, and the Cochrane Library from inception until May
      2015. Data was extracted according to PRISMA guidelines and an online, published
      protocol. Four studies are included in this review. One study found an
      association between expectations and satisfaction. Different measures of
      expectation and satisfaction were used in all studies. To date, there is no
      consensus on how expectations or satisfaction should be measured, and a large
      number of studies that have the available information failed to conduct the
      relevant sub-group analysis. Further elucidation and consensus of how to measure
      expectations and satisfaction around joint replacement would aid this area of
      study greatly. On the basis of the current evidence it appears expectations have
      a small effect, if any, on satisfaction after knee replacement. 

PMID- 27026865
TI  - Degradation of oil products in a soil from a Russian Barents hot-spot during
      electrodialytic remediation.
AB  - A highly oil-polluted soil from Krasnoe in North-West Russia was used to
      investigate the degradation of organic pollutants during electrodialytic
      remediation. Removal efficiencies were up to 70 % for total hydrocarbons (THC)
      and up to 65 % for polyaromatic hydrocarbons (PAH). Relatively more of the
      lighter PAH compounds and THC fractions were degraded. A principal component
      analysis (PCA) revealed a difference in the distribution of PAH compounds after
      the remediation. The observed clustering of experiments in the PCA scores plot
      was assessed to be related to the stirring rate. Multivariate analysis of the
      experimental settings and final concentrations in the 12 experiments revealed
      that the stirring rate of the soil suspension was by far the most important
      parameter for the remediation for both THC and PAH. Light was the second most
      important variable for PAH and seems to influence degradation. The experimental
      variables current density and remediation time did not significantly influence
      the degradation of the organic pollutants. Despite current density not
      influencing the remediation, there is potential for degrading organic pollutants
      during electrodialytic removal of heavy metals, as long as a stirred set-up is
      applied. Depending on remediation objectives, further optimisation may be needed
      in order to develop efficient remediation strategies. 

PMID- 27026866
TI  - Development of an Escherichia coli-Lactobacillus casei shuttle vector for
      heterologous protein expression in Lactobacillus casei.
AB  - There is an increasing interest to develop various lactic acid bacteria (LAB)
      species as mucosal delivery vehicles, for which the development of a variety of
      cloning and expression systems for these bacteria is of primary importance. This
      study reports the complete nucleotide sequence of the cryptic plasmid pRCEID7.6
      derived from the chicken probiotic LAB strain Lactobacillus casei TISTR1341.
      Sequence analysis and comparison showed that pRCEID7.6 is composed of nine
      putative open reading frames. The replicon origin of pRCEID7.6 consisted of
      untranslated origin of replication and translated replication protein B
      sequences. This region was used to construct Escherichia coli/L. casei shuttle
      vectors carrying erythromycin and chloramphenicol resistance genes as selective
      markers. Segregation and structural stability of the vectors in L. casei was
      sufficient for most genetic applications. The feasibility of this vector for
      heterologous protein expression in L. casei was determined by cloning in pRCEID
      LC7.6, the gene encoding the nucleocapsid protein (NP), from the influenza A
      virus under the control of the homologous promoter from the lactate dehydrogenase
      gene. L. casei carrying this recombinant plasmid was shown to successfully
      express the NP protein. Therefore, this shuttle vector can be used for further
      study in the development of mucosal delivery vehicles. 

PMID- 27026867
TI  - Steroids, lidocain and ioxaglic acid modify the viscosity of hyaluronic acid: in
      vitro study and clinical implications.
AB  - BACKGROUND: Viscosupplementaion by intra-articular injection of hyaluronic acid
      (HA) is a therapeutic modality for treating osteoarthritis of the knee, of the
      hip and less frequently of other joints. During viscosupplementation, it is usual
      to inject other drugs, without knowing whether this association may have a
      deleterious effect thereon. The rheological properties of a viscosupplement are
      highly dependent on the product [molecular weight * concentration] of HA.
      Therefore, any reduction of its viscoelastic properties is related either to a
      decrease of its concentration or/and of its molecular weight. The presence of
      other molecules can create favorable or unfavorable molecular interactions with
      HA. The objective of the study was to investigate the effect of products, that
      are commonly associated with HA (corticosteroids, lidocain, iodinated contrast
      media), on the rheological behavior of HA, then to try drawing practical
      conclusions. METHODS: The rheological behavior of both a linear and a cross
      linked HA, was studied before and after mixing with different volumes (ratio
      1:0.5-1:4) of the following compounds: phosphate buffered saline (PBS, as a
      control), cortivazol, triamcinolone hexacetonide, lidocain chlorhydrate and
      meglumine ioxaglate. The flow curve of the different samples was obtained using a
      measuring method based on a constant shear rate. RESULTS: Whatever the dilution
      and the added molecule were, viscosity of the cross-linked viscosupplement
      remained much higher than that of the linear one. Addition of PBS at a ratio 1:1
      caused a dramatic decrease (up to 97.5 %) of HA viscosity. Cortivazol and
      lidocain had a similar effect than PBS on linear HA. Both were much deleterious
      on cross-linked HA viscosity. Among corticosteroids, triamcinolone decreased much
      less HA viscosity than cortivazol. The effect of meglumine ioxaglate was dose
      dependent. Up to a ratio 1:1 viscosity of the linear HA remained above the
      dilution effect. On the cross-linked HA, the deleterious effect of the contrast
      agent was evident as soon as a ratio 1:1 and became very marked at 1:2.
      CONCLUSION: HA viscosity varies widely in presence of other molecules. These
      changes are due to both dilution and molecular interactions. This study suggests
      that addition of other molecules with HA can lead to a major decrease of its
      viscosity. However, provided to respect a maximum ratio of 1:1, the contrast
      medium and triamcinolone seem to have no major deleterious effect on the
      viscosity level, especially on crosslinked HA. The study also suggests a
      deleterious effect of lidocain on the cross-linked HA. These in vitro data
      suggest that drugs associations must be avoided when they are not essential.
      However, clinical trials are needed to determine whether these rheological
      changes may have a significant impact on the clinical outcome.

PMID- 27026868
TI  - Ammonia and salinity tolerance of Penaeus monodon across eight breeding families.
AB  - Ammonia nitrogen and salinity tolerance of Penaeus monodon from eight selected
      breeding families were evaluated at the concentration of 67.65 mg L(-1) ammonia-N
      and reducing salinity from 15 to 0 0/00. The final survival of family A (88.67 +/
      9.81 %) was highest, and the final survival of family B was lowest (24.33 +/-
      14.01 %) after the ammonia tolerance test. Upon completing the sudden drop
      salinity test from 15 to 0 0/00, the highest survival was observed in family B
      (98.00 +/- 1.73 %), and the lowest survival was found in family H (18.00 +/- 1.73
      %). Family A showed the strongest ability to tolerate ammonia stress, and family
      B showed the strongest tolerance to low salinity. This study suggests that the
      tolerance of salinity and ammonia nitrogen varied between breeding families.
      Results from the present study provide useful information towards selective
      breeding in shrimp in aquaculture for environmental tolerance. 

PMID- 27026869
TI  - Simultaneous detection of lysine metabolites by a single LC-MS/MS method:
      monitoring lysine degradation in mouse plasma.
AB  - Detection and quantification of lysine degradation metabolites in plasma is
      necessary for the diagnosis and follow-up of diseases such as pyridoxine
      dependent epilepsy. The principal metabolites involved in the disease are related
      to the first steps of lysine oxidation, either through the saccharopine or the
      pipecolate pathways. Currently, there are three different analytical methods used
      to assess the content of these metabolites in urine and plasma, but they require
      different sample preparations and analytical equipment. Here, we describe a
      protocol that calls for a simple sample preparation and uses liquid
      chromatography tandem mass spectrometry (LC-MS/MS) that allows simultaneous
      detection and quantification of underivatized l-saccharopine, l-aminoadipic acid,
      l-pipecolic acid, piperideine-6-carboxylate, l-glutamic acid, and pyridoxal-5
      phosphate in plasma samples. To validate the method we analyzed the time course
      degradation after intraperitoneal injection of l-lysine in C57BL/6/J mice. We
      observed that the degradation of lysine through the saccharopine pathway reached
      a maximum within the first 2 h. At this time point there was an increase in the
      levels of the metabolites saccharopine, aminoadipic acid, and pipecolic acid by 3
      , 24- and 3.4-fold, respectively, compared to time zero levels. These metabolites
      returned to basal levels after 4-6 h. In conclusion, we have developed a LC-MS/MS
      approach, which allows simultaneous analysis of lysine degradation metabolites
      without the need for derivatization. 

PMID- 27026870
TI  - Heavy metals bioaccumulation in Berseem (Trifolium alexandrinum) cultivated in
      areas under intensive agriculture, Punjab, India.
AB  - Berseem (Trifolium alexandrinum) is one of the main fodder crops of Punjab,
      India. But due to the heavy metal contamination of agricultural soils by
      anthropogenic activities, there is rise in metal bioaccumulation in crops like
      Berseem. In addition to human influence, heavy metal contents in soil are highly
      dependent on soil characteristics also. Therefore a study was conducted in areas
      having intensive agricultural practices to analyze physico-chemical
      characteristics of soils under Berseem cultivation and heavy metal
      bioaccumulation in Berseem. The studied soils were alkaline, sandy in texture and
      low in soil organic matter. Among the studied heavy metals (Cr, Cu, Cd, Co and
      Pb) in soil and Berseem, Cr content in Berseem was found to be above maximum
      permissible limits. Soil to Berseem metal bioaccmulation factor (BAF) was above 1
      for Cr, Cu, Cd and Co in many samples and highest BAF was found for Co (4.625).
      Hence it can be concluded that Berseem from studied areas was unsafe for animal
      consumption. 

PMID- 27026871
TI  - The outcome and parents-based cosmetic satisfaction following fixation of
      paediatric supracondylar humerus fractures treated by closed method with or
      without small medial incision.
AB  - Supracondylar humerus fractures are common in children. Displaced fractures are
      usually treated with closed reduction and cross pin fixation. But, medial pinning
      may cause the ulnar nerve injury. The aim of this study was to compare the
      parents-based cosmetic satisfaction of the incision scars in children with
      displaced supracondylar humerus fractures treated by closed reduction and cross
      pin fixation with or without small medial incision. We retrospectively reviewed
      the medical records of 72 children with displaced supracondylar humerus fractures
      treated two different closed reduction and percutaneous pinning methods at our
      institution from January 2010 through December 2013. A group has 36 patients
      treated with small medial incision and crossed K-wires fixation after closed
      reduction. The other group has 36 patients treated with closed reduction and K
      wires fixation. At the final follow-up, the patients were evaluated
      radiologically and clinically with Flynn's criteria. Furthermore, a visual
      analogue scale was used to determine of the parents-based cosmetic satisfaction
      score. All fractures healed without major complications at the final clinical and
      radiological assessment. Although, between the two groups did not differ in terms
      of Flynn cosmetic and functional outcomes, there were statistically significant
      differences between both groups according to the parents-based cosmetic
      satisfaction scores. The closed reduction and crossed pin fixation without small
      medial incision should be preferred first because of better the parents-based
      cosmetic satisfaction. 

PMID- 27026872
TI  - High capacity data hiding scheme based on (7, 4) Hamming code.
AB  - Aiming to embed large amount of data while minimize the sum of costs of all
      changed pixels, a novel high capacity data hiding scheme based on (7, 4) Hamming
      code is realized by a family of algorithms. Firstly, n (n = 1, 2, 3) cover pixels
      are assigned to one set according to the payload. Then, 128 binary strings of
      length seven are divided into eight sets according to the syndrome of every
      binary string. Binary strings that share the same syndrome are classified into
      one set. Finally, a binary string in a certain set determined by the data to be
      embedded is chosen to modify some of the least significant bits of the n cover
      pixels. The experimental results demonstrate that the image quality of the
      proposed method with high embedding payload is superior to those of the related
      schemes. 

PMID- 27026874
TI  - Difference-based ridge-type estimator of parameters in restricted partial linear
      model with correlated errors.
AB  - In this article, a generalized difference-based ridge estimator is proposed for
      the vector parameter in a partial linear model when the errors are dependent. It
      is supposed that some additional linear constraints may hold to the whole
      parameter space. Its mean-squared error matrix is compared with the generalized
      restricted difference-based estimator. Finally, the performance of the new
      estimator is explained by a simulation study and a numerical example. 

PMID- 27026873
TI  - Canadian CT head rule and New Orleans Criteria in mild traumatic brain injury:
      comparison at a tertiary referral hospital in Japan.
AB  - We compared Canadian computed tomography (CT) head rule (CCHR) and New Orleans
      Criteria (NOC) in predicting important CT findings in patients with mild
      traumatic brain injury (TBI). We included 142 consecutive patients with mild TBI
      [Glasgow coma scale (GCS) 13-15] who showed at least one of the risk factors
      stated in the CCHR or the NOC. We introduced two scores: a Canadian from the CCHR
      and a New Orleans from the NOC. A patient's score represented a sum of the number
      of positive items. We examined the relationship between scores or items and the
      presence of important CT findings. Only the Canadian was significantly associated
      with important CT findings in multivariate analyses and showed higher area under
      the receiver operating characteristic curve (AUC) either in all 142 patients (GCS
      13-15: P = 0.0130; AUC = 0.69) or in the 67 with a GCS = 15 (P = 0.0128, AUC =
      0.73). Of items, ">60 years" or ">=65 years" included in either guideline was the
      strongest predictor of important CT finding, followed by "GCS < 15 after 2 h"
      included only in the CCHR. In a tertiary referral hospital in Japan, CCHR had
      higher performance than the NOC in predicting important CT findings. 

PMID- 27026875
TI  - Abundance and dispersal of Heteronychus arator (Coleoptera: Scarabaeidae) in
      maize fields under different fertilizer treatments.
AB  - The invasive African black beetle Heteronychus arator F. is a serious pest of
      crops in Tropical and sub Tropical regions, including East Africa. Literature on
      ecology of this pest in Sub Saharan Africa is scarce. Dispersal and abundance of
      H. arator were determined in maize fields in Njombe Region, in the Southern
      highlands of Tanzania, from December 2013 to May 2014. Adults of H. arator were
      collected monthly by hand picking and pitfall traps. Results showed that larvae
      were present throughout the growing season, with low population at planting and
      peak period coinciding with optimum soil moisture. The abundance of adults varied
      with time, with high peaks recorded in January. Abundance of both larvae and
      adults were significantly affected by fertilizer type, with high populations in
      farmyard manure. The type of fertilizer significantly affected dispersal of H.
      arator. A high number of beetles moved significantly longer distances in farmyard
      and inorganic fertilizer compared to bioslurry a day after release. Abundance of
      of beetles was negatively correlated with rainfall but positively correlated with
      average temperature, while abundance of larvae was positively correlated with
      rainfall. The results provide useful input into management of H. arator under
      different fertilizer practices and weather conditions. 

PMID- 27026876
TI  - Multicentric reticulohistiocytosis (MRH): case report with review of literature
      between 1991 and 2014 with in depth analysis of various treatment regimens and
      outcomes.
AB  - Multicentric reticulohistiocytosis is a rare disease affecting skin and joints
      primarily and rarely other organs. We present a case report of this disease and
      an extensive review of the literature. We reviewed the data between 1991 and 2014
      and extracted 52 individual cases. Only articles in English were chosen after
      checking for relevance. The articles were studies and data was extracted into
      excel spread sheets and later used to compute such variables like frequency, mean
      and percentage of distribution of various clinical manifestations. The treatments
      used in these articles were critically analyzed and graded for their relative
      efficacy for skin and joint manifestations. The grades were 0 = worse, 1 = no
      benefit/condition remained same, 2 = improvement without resolution, and 3 =
      resolution. This article also reports the demographic, clinical, laboratory and
      pathological data from the reviewed articles. Authors attempted to discuss the
      findings of this review in depth to help manage this condition and proposed a
      treatment algorithm to help clinicians approach this rare and challenging
      disease. 

PMID- 27026877
TI  - Molecular cloning, structural and expression profiling of DlRan genes during
      somatic embryogenesis in Dimocarpus longan Lour.
AB  - To clone and examine expression profiles of DlRan genes during somatic
      embryogenesis in Dimocarpus longan Lour. Thirty cDNA sequences and two genomic
      sequences encoding DlRan proteins were isolated from longan embryogenic cultures.
      Structural analysis of DlRan genes revealed that the longan Ran gene family is
      more expanded than that of Arabidopsis. Expression analysis of DlRan genes during
      somatic embryogenesis uncovered a high abundance of DlRan genes in early
      embryogenic cultures and heart- and torpedo-shaped embryos. The expression of
      DlRan genes in embryogenic calli was affected by exogenous 2,4
      dichlorophenoxyacetic acid treatment. DlRan is involved in 2,4-D induced somatic
      embryogenesis and development of somatic embryos in longan. 

PMID- 27026878
TI  - Potential problems and recommendations regarding substitution of generic
      antiepileptic drugs: a systematic review of literature.
AB  - Despite the availability of generic antiepileptic drugs (AEDs), still patients
      and neurologists hesitate to make a switch due to assorted reasons. The
      objectives of this review were to evaluate the risks associated with the generic
      substitution of AEDs. In this context, we also summarized the recommendations of
      various international societies to treat epileptic patients. We used a number of
      electronic databases to identify the relevant published studies which
      demonstrated the potential problems and recommendations regarding generic
      substitution of AEDs. Of 204 articles found initially, 153 were selected for
      additional review. Subsequently, 68 articles were finally selected. This review
      concluded that potential problems linked with the generic substitution of AEDs
      could be bioequivalence issues, failure of drug therapy, emergence of adverse
      events and increase in the frequency of seizures. The reasons could be the
      pharmacokinetics properties of AEDs and unique characteristics of some epilepsy
      patients. Consequently, the generic substitution of AEDs affects the successful
      treatment and quality of life of the patients. Various guidelines recommend the
      well-controlled epileptic patients to avoid switching from brand-to-generic
      products, generic-to-brand products or generic to some other generic products. 

PMID- 27026879
TI  - Exercise volume and aerobic fitness in young adults: the Midwest Exercise Trial
      2.
AB  - To examine the effect of exercise volume at a fixed intensity on changes in
      aerobic fitness. Ninety-two overweight/obese individuals (BMI 25-40 kg m(2)), age
      18-30 years, 50 % women, completed a 10 mo, 5 d wk(-1) supervised exercise
      intervention at 2 levels of exercise energy expenditure (400 or 600 kcal session(
      1)) at 70-80 % heart rate (HR) max. Exercise consisted primarily of
      walking/jogging on motor-driven treadmills. The duration and intensity of all
      exercise sessions were verified by a downloadable HR monitor set to collect HR in
      1-min epochs. All participants were instructed to continue their typical patterns
      of non-exercise physical activity and dietary intake over the duration of the 10
      mo intervention. Maximal aerobic capacity (indirect calorimetry) was assessed on
      a motor-driven treadmill using a modified Balke protocol at baseline, mid-point
      (5 mo), and following completion of the 10 mo intervention. VO2 max (L min(-1))
      increased significantly in both the 400 (11.3 %) and 600 kcal session(-1) groups
      (14 %) compared to control (-2.0 %; p < 0.001); however, the differences between
      exercise groups were not significant. Similar results were noted for change in
      relative VO2 max (mL kg(-1) min(-1)); however, the magnitude of change was
      greater than for absolute VO2 max (L min(-1)) (400 group = 18.3 %; 600 group =
      20.2 %) due to loss of body weight over the 10-mo intervention in both exercise
      groups. Our results indicate that exercise volume was not associated with change
      in aerobic fitness in a sample of previously sedentary, overweight and obese
      young adults. 

PMID- 27026880
TI  - Experimental vitamin B12 deficiency in a human subject: a longitudinal
      investigation of the performance of the holotranscobalamin (HoloTC, Active-B12)
      immunoassay.
AB  - Based on Victor Herbert's model for sequential stages in the development of
      vitamin B12 deficiency, the holotranscobalamin (HoloTC) immunoassay has
      controversially been promoted as a more specific and sensitive replacement for
      the total vitamin B12 test, for the diagnosis of deficiency. There have been no
      longitudinal studies, by means of experimental cobalamin deficiency, because
      ethical considerations prevent such risky studies on patients or healthy human
      volunteers. The objective was to provide a detailed record of the response of
      HoloTC, compared to total vitamin B12 and metabolites, to the development of
      experimental vitamin B12 deficiency in an initially replete human subject. This
      54 year old male, with a vitamin B12 deficiency possibly caused by a defect in
      the intracellular cobalamin metabolism, ensured an initially replete condition by
      means of oral doses of cyanocobalamin supplements at 1000 MUg/day for 12 weeks.
      The subject then depleted himself of vitamin B12, by withholding treatment and
      using a low-cobalamin diet, until significant metabolic disturbances were
      observed. The responses of serum total vitamin B12 and HoloTC and the two
      metabolites, plasma methylmalonic acid and homocysteine, were monitored by weekly
      blood tests. HoloTC was not significantly more sensitive than either total serum
      vitamin B12 or total homocysteine, and was much less sensitive than methylmalonic
      acid. HoloTC decreased from an initial concentration of >128 pmol/L to a minimum
      of 33 pmol/L on day 742, the only day on which it fell below the lower limit of
      the reference interval. Total vitamin B12 decreased from an initial concentration
      of 606 pmol/L to a minimum of 171 pmol/L on day 728. Total homocysteine increased
      from an initial concentration of 8.4 MUmol/L to a maximum of 14.2 MUmol/L on day
      609. Methylmalonic acid unexpectedly contained four distinct peaks; initially at
      0.17 MUmol/L, it first exceeded the upper limit of the reference interval on day
      386, finally reaching a maximum peak of 0.90 MUmol/L on day 658. The results of
      this experiment are inconsistent with Herbert's hypothesis that HoloTC is the
      earliest marker of vitamin B12 deficiency, and therefore do not support his model
      for the staged development of vitamin B12 deficiency. 

PMID- 27026881
TI  - Efficient conversion of xylose to ethanol by stress-tolerant Kluyveromyces
      marxianus BUNL-21.
AB  - The fermentation ability of thermotolerant Kluyveromyces marxianus BUNL-21
      isolated in Laos was investigated. Comparison with thermotolerant K. marxianus
      DMKU3-1042 as one of the most thermotolerant yeasts isolated previously revealed
      that the strain possesses stronger ability for conversion of xylose to ethanol,
      resistance to 2-deoxyglucose in the case of pentose, and tolerance to various
      stresses including high temperature and hydrogen peroxide. K. marxianus BUNL-21
      was found to have ethanol fermentation activity from xylose that is slightly
      lower and much higher than that of Scheffersomyces stipitis (Pichia stipitis) at
      30  degrees C and at higher temperatures, respectively. The lower ethanol
      production seems to be due to large accumulation of acetic acid. The possible
      mechanism of acetic acid accumulation is discussed. In addition, it was found
      that both K. marxianus strains produced ethanol in the presence of 10 mM
      hydroxymethylfurfural or furfural, at a level almost equivalent to that in their
      absence. Therefore, K. marxianus BUNL-21 is a highly competent yeast for high
      temperature ethanol fermentation with lignocellulosic biomass. 

PMID- 27026882
TI  - Cytogenetic study of diploid and induced tetraploid in Korean rose bitterling,
      Rhodeus uyekii.
AB  - In this study, we induced tetraploidy in Korean rose bitterling, Rhodeus uyekii,
      by applying various hydrostatic pressure shock conditions. Tetraploidy was not
      induced under 4500 psi pressure treatment in any experimental group. Instead, the
      induction rate of tetraploidy was highest under 7500 psi hydrostatic pressure
      treatment. As a result, when the processing method was similar and as the process
      time increased, the induction rate of each experimental group increased; however,
      there was no significant difference (P > 0.05). The production rate was 3.1 %,
      which was highest in all experimental groups exposed to 6000 psi for 10 min after
      being fertilized for 100 min. The production rate was highest in the experimental
      groups treated with hydrostatic pressure alone, whereas the production rate was
      lowest in groups treated under hydrostatic pressure with chemical treatment. The
      abnormal rate of all experimental groups treated with 7500 psi for 20 min was
      very high, at about 5 %. Based on these studies, only hydrostatic pressure shock
      was considered effective at inducing tetraploidy based on the calculated
      hatching, abnormal, and induction rates. The most effective condition for
      inducing tetraploidy was 6000 psi of hydrostatic pressure shock for 10 min after
      being fertilized for 100 min. The chromosome number of the induced tetraploid
      Korean rose bitterling was 4n = 96, while that of the diploid was 2n = 48. In the
      diploid, there were 1 or 2 nucleoli in the cells, whereas the induced tetraploids
      contained 1, 2, 3, or 4. The DNA content of tetraploids and diploids were 3.68 +/
      0.009 pg/nucleus and 1.84 +/- 0.019 pg/nucleus, respectively, according to flow
      cytometric analysis. The DNA content and chromosome number of the tetraploids
      were twice that of the diploids. 

PMID- 27026883
TI  - Uncommon presentation of potential medication-related osteonecrosis of the jaw.
AB  - BACKGROUND: This article presents a patient with potential atypical medication
      related osteonecrosis of the jaw and reviews related literatures. CASE
      PRESENTATION: A 52-year-old male showed pain in the left buccal area and had
      numbness on the left lower lip area. He received medications having anti
      angiogenic effect for 4 years. He did not receive irradiation of the jaw regions.
      In histological view, most of the adipocytes were destroyed and disappeared in
      the scanty vascular marrow tissue, resulting in the replacement of the fatty
      necrosis with variable sized vacuolated empty spaces. In the immunohistochemistry
      analysis, the infiltrated macrophages into the marrow stromal tissue were
      strongly positive for lysozymes. These findings demonstrate that the presented
      osteonecrosis underwent a chronic and persistent granulomatous inflammatory
      reaction. CONCLUSIONS: We conclude that the present case might have been caused
      by anti-angiogenic drug abuse, affecting the reduction of the mandibular marrow
      vascularity and subsequently inducing fatty necrosis and an extensive osteolytic
      change of the mandible.

PMID- 27026884
TI  - Robotic microlaryngeal surgery: a new retractor that provides improved access to
      the glottis.
AB  - Robotic surgery has become the standard of care for many procedures outside of
      otolaryngology, and now is gaining momentum within our specialty. The robot has
      several advantages to human hands, including removal of tremor and better access
      to lesions due to increased degree of movement of the articulated instruments.
      The glottis has rarely been addressed using robotics because access was
      previously thought to be difficult. We present a case report using the modular
      oral retractor system to perform robotic microlaryngeal surgery. 

PMID- 27026885
TI  - A sutureless technique using cyanoacrylate adhesives when creating a stoma for
      extremely low birth weight infants.
AB  - PURPOSE: Intestinal perforation and necrotizing enterocolitis (NEC) are neonatal
      intestinal emergencies that are especially common in premature infants. While
      prompt surgical intervention, including stoma creation, is often required, the
      optimal surgical treatment has been controversial because of the substantial
      risks related to the stoma creation and management. The use of a tissue adhesive
      may have some advantages over the use of sutures when creating an intestinal
      stoma in extremely low birth weight (ELBW) infants. The purpose of this report
      was to present a novel approach for creating a stoma using a tissue adhesive in
      ELBW infants. METHODS: A total of eight ELBW infants that underwent laparotomy
      with the creation of intestinal stomas using cyanoacrylate adhesive at our
      institution between 2009 and 2014 were enrolled. The clinical parameters,
      including the length of the operation, intra- and postoperative complications and
      the outcomes were evaluated. RESULTS: The median body weight and gestational age
      at birth were 630 g and 24.3 weeks, respectively. The median age at referral was
      11.5 days. The median length of the procedure was 58.5 min, including the
      inspection and resection of the intestine. All procedures were completed without
      any intraoperative complications. There were no postoperative complications
      associated with the stoma. Two patients died of the associated septic status.
      CONCLUSIONS: Sutureless enterostomy using cyanoacrylate adhesive is a simple
      technique which has the potential to reduce the incidence of complications
      related to the intestinal stoma in ELBW infants.

PMID- 27026886
TI  - Arthroscopic treatment of non-homogeneous calcifying tendinitis of the rotator
      cuff.
AB  - The purpose of this study is to investigate the clinical outcome of arthroscopic
      treatment for patients with non-homogeneous infiltrated calcifying tendinitis of
      the rotator cuff (type III), and to assess the optimal method for this
      arthroscopic treatment. We retrospectively reviewed the charts of 81 patients who
      underwent arthroscopic treatment for non-homogeneous infiltrated calcifying
      tendinitis of the rotator cuff (type III). Patients were divided into two groups:
      Group A (n = 31) consisted of patients who underwent excision of calcification,
      and Group B comprised patients who underwent acromioplasty alone (n = 50). The
      clinical outcome of treatment was assessed using Constant-Murley score. Twenty
      three of the 81 patients were males and 58 were females. The mean duration of
      symptoms from onset to the first clinic visit was 3.88 years (SD +/- 3.06 years).
      The right side was involved in 47 patients, the left side in 34 patients, and
      none had bilateral involvement. Patients from Group B had higher 16 improvement
      of their Constant-Murley score (from 48.96 to 88.06) when 17 compared to group A
      (from 45.39 to 67.23). Treatment of type III calcifying tendinitis is different
      than type I and II. Subacromial decompression may be considered in all patients
      suffering from type III non-homogeneous infiltrated calcifying tendinitis of the
      shoulder. 

PMID- 27026887
TI  - Sports teams as complex adaptive systems: manipulating player numbers shapes
      behaviours during football small-sided games.
AB  - Small-sided and conditioned games (SSCGs) in sport have been modelled as complex
      adaptive systems. Research has shown that the relative space per player (RSP)
      formulated in SSCGs can impact on emergent tactical behaviours. In this study we
      adopted a systems orientation to analyse how different RSP values, obtained
      through manipulations of player numbers, influenced four measures of
      interpersonal coordination observed during performance in SSCGs. For this purpose
      we calculated positional data (GPS 15 Hz) from ten U-15 football players
      performing in three SSCGs varying in player numbers (3v3, 4v4 and 5v5). Key
      measures of SSCG system behaviours included values of (1) players' dispersion,
      (2) teams' separateness, (3) coupling strength and time delays between
      participants' emerging movements, respectively. Results showed that values of
      participants' dispersion increased, but the teams' separateness remained
      identical across treatments. Coupling strength and time delay also showed
      consistent values across SSCGs. These results exemplified how complex adaptive
      systems, like football teams, can harness inherent degeneracy to maintain similar
      team spatial-temporal relations with opponents through changes in inter
      individual coordination modes (i.e., players' dispersion). The results imply that
      different team behaviours might emerge at different ratios of field
      dimension/player numbers. Therefore, sport pedagogists should carefully evaluate
      the effects of changing RSP in SSCGs as a way of promoting increased or decreased
      pressure on players. 

PMID- 27026888
TI  - Interactive evolutionary computation with minimum fitness evaluation requirement
      and offline algorithm design.
AB  - In interactive evolutionary computation (IEC), each solution is evaluated by a
      human user. Usually the total number of examined solutions is very small. In some
      applications such as hearing aid design and music composition, only a single
      solution can be evaluated at a time by a human user. Moreover, accurate and
      precise numerical evaluation is difficult. Based on these considerations, we
      formulated an IEC model with the minimum requirement for fitness evaluation
      ability of human users under the following assumptions: They can evaluate only a
      single solution at a time, they can memorize only a single previous solution they
      have just evaluated, their evaluation result on the current solution is whether
      it is better than the previous one or not, and the best solution among the
      evaluated ones should be identified after a pre-specified number of evaluations.
      In this paper, we first explain our IEC model in detail. Next we propose a
      ([Formula: see text])ES-style algorithm for our IEC model. Then we propose an
      offline meta-level approach to automated algorithm design for our IEC model. The
      main feature of our approach is the use of a different mechanism (e.g., mutation,
      crossover, random initialization) to generate each solution to be evaluated.
      Through computational experiments on test problems, our approach is compared with
      the ([Formula: see text])ES-style algorithm where a solution generation mechanism
      is pre-specified and fixed throughout the execution of the algorithm. 

PMID- 27026889
TI  - Neutrophil gelatinase-associated lipocal in protein levels as an acute
      appendicitis biomarker in children.
AB  - OBJECTIVE: Appendicitis is very commonly encountered in emergency clinics. There
      is an urgent need for early and accurate predictive biomarkers of appendicitis in
      order to save lives, because currently-available biomarkers are imprecise and
      their delayed response impairs the ability of emergency doctors and pediatric
      surgeons to provide timely and potentially effective therapies. This study was
      performed to determine whether changes in the blood levels of neutrophil
      gelatinase-associated lipocalin (NGAL) can help to diagnose acute appendicitis in
      children and distinguish acute appendicitis from abdominal pain. METHODS: Sixty
      children were enrolled and divided into three groups, with 20 patients per group:
      Group 1 (patients with appendicitis), Group 2 (patients with abdominal pain) and
      Group 3 (control). Blood NGAL levels were determined by ELISA. RESULTS: The basal
      average serum NGAL levels were 8.2 ng/ml for Group 1, 3.9 ng/ml for Group 2, and
      3.3 ng/ml for Group 3. Twenty-four and 72 h after surgery the levels were 5.1 and
      2.8 ng/ml, respectively, in Group 1, 2.9 and 2.8 ng/ml in Group 2, and 2.6, 2.7
      ng/ml in Group 3. Setting the cut-off point to 7 generated an area under the
      receiving operating curve (ROC) curve at 95 % confidence interval with 77.3 %
      sensitivity and 97.4 % specificity. CONCLUSION: These data indicate a significant
      difference in NGAL values between basal and postoperative measurements in
      appendicitis patients (p < 0.05). The ROC curve results showed that NGAL is a
      promising novel biomarker for the differential diagnosis of acute appendicitis
      from abdominal pain.

PMID- 27026890
TI  - "Pointing forehead": a new physical sign in migraine.
AB  - This study was designed to compare the presence of seven clinical signs in a
      group of patients with migraine with that of patients with non-migraine headache.
      Migraine is sometimes misdiagnosed. Therefore additional features are useful to
      improve the diagnostic accuracy of migraine. A cross sectional descriptive study
      was conducted in a group of 709 outpatients with headache. The physical signs
      were named as A-G. These were carefully observed certain gestures exhibited by
      patients themselves when they describe their headache. Sign A (pointing right
      side of the forehead) and sign B (pointing left side of the forehead) were
      significantly higher in patients with migraine (Sign A positive-123/339, Chi
      square-15.784, p < 0.001; Sign B positive-146/339, Chi-square-20.813, p < 0.001).
      Sign F (keeping the head on a table) was significantly higher in patients with
      non-migraine headache (Sign F positive-132/370, Chi-square-12.954, p < 0.001).
      Sign A was more commonly associated with unilateral, severe headache which lasted
      for a longer period of time. However sign B was more commonly associated with
      unilateral, severe headache only. Sign C was significant in patients who had
      bilateral headache in both migraine and non-migraine groups than unilateral
      headache. It is concluded that pointing right or left side of forehead when the
      patient describes his or her headache is a characteristic sign of migraine.
      Keeping the head on the table during an attack of headache is not a
      characteristic sign of migraine. 

PMID- 27026892
TI  - Perturbational blowup solutions to the compressible Euler equations with damping.
AB  - BACKGROUND: The N-dimensional isentropic compressible Euler system with a damping
      term is one of the most fundamental equations in fluid dynamics. Since it does
      not have a general solution in a closed form for arbitrary well-posed initial
      value problems. Constructing exact solutions to the system is a useful way to
      obtain important information on the properties of its solutions. METHOD: In this
      article, we construct two families of exact solutions for the one-dimensional
      isentropic compressible Euler equations with damping by the perturbational
      method. The two families of exact solutions found include the cases [Formula: see
      text] and [Formula: see text], where [Formula: see text] is the adiabatic
      constant. RESULTS: With analysis of the key ordinary differential equation, we
      show that the classes of solutions include both blowup type and global existence
      type when the parameters are suitably chosen. Moreover, in the blowup cases, we
      show that the singularities are of essential type in the sense that they cannot
      be smoothed by redefining values at the odd points. CONCLUSION: The two families
      of exact solutions obtained in this paper can be useful to study of related
      numerical methods and algorithms such as the finite difference method, the finite
      element method and the finite volume method that are applied by scientists to
      simulate the fluids for applications.

PMID- 27026891
TI  - An intrapleural administration of zoledronic acid for inoperable malignant
      mesothelioma patients: a phase I clinical study protocol.
AB  - BACKGROUND: The third generation of bisphosphonates is clinically in use for
      patients of osteoporosis or malignancy-linked hypercalcemia. The agents can also
      produce anti-tumor effects on bone metastasis of several types of tumors. We
      recently found that one of the agents achieved cytotoxicity to mesothelioma in
      vitro and in an orthotopic animal model. Mesothelioma is resistant to a number of
      chemotherapeutic agents, and suppression of local tumor growth is beneficial to
      the patients since metastasis to extra-thoracic organs is relatively infrequent
      until a late stage. METHODS/DESIGN: We demonstrated in an orthotopic mouse model
      that an intrapleural but not intravenous injection of zoledronic acid, one of the
      third generation bisphosphonates, at a clinically equivalent dose suppressed the
      tumor growth. Nevertheless, a high concentration of zoledronic acid administrated
      in the pleural cavity produced pleural adhesion. We also showed that zoledronic
      acid produced synergistic cytotoxic effects with cisplatin, the first-line
      chemotherapeutic agent for mesothelioma. We then planned to conduct a phase I
      clinical study to investigate any adverse effects and a possible clinical
      benefits produced by an intrapleural administration of zoledronic acid to
      mesothelioma patients who became resistant to the first-line chemotherapeutic
      agents. The clinical trial is a dose escalation study starting with 0.4, 1, 4, 8
      and 16 mg per person since safety of administration of zoledronic acid into the
      pleural cavity remains unknown. Each dose group consists of three persons and the
      protocol allows to repeat administration of the same dose into the pleural cavity
      at a 4-weeks interval. DISCUSSION: We will conduct a possible combinatory study
      of intrapleural administration of zoledronic acid and systemic administration of
      the first-line agent to a chemotherapy-naive patient based on the maximum
      tolerance dose of zoledronic acid determined by the present clinical trial. We
      propose that administration of bisphosphonates in a closed cavity is a treatment
      strategy for tumors developed in the cavity probably through the direct cytotoxic
      activity. TRIAL REGISTRATION: UMIN clinical trials registry, Japan. Register ID:
      UMIN8093.

PMID- 27026893
TI  - Understanding the relationship between Kano model's customer satisfaction scores
      and self-stated requirements importance.
AB  - Customer satisfaction is the result of product quality and viability. The place
      of the perceived satisfaction of users/customers for a software product cannot be
      neglected especially in today competitive market environment as it drives the
      loyalty of customers and promotes high profitability and return on investment.
      Therefore understanding the importance of requirements as it is associated with
      the satisfaction of users/customers when their requirements are met is worth the
      pain considering. It is necessary to know the relationship between customer
      satisfactions when their requirements are met (or their dissatisfaction when
      their requirements are unmet) and the importance of such requirement. So many
      works have been carried out on customer satisfaction in connection with the
      importance of requirements but the relationship between customer satisfaction
      scores (coefficients) of the Kano model and users/customers self-stated
      requirements importance have not been sufficiently explored. In this study, an
      attempt is made to unravel the underlying relationship existing between Kano
      model's customer satisfaction indexes and users/customers self reported
      requirements importance. The results of the study indicate some interesting
      associations between these considered variables. These bivariate associations
      reveal that customer satisfaction index (SI), and average satisfaction
      coefficient (ASC) and customer dissatisfaction index (DI) and average
      satisfaction coefficient (ASC) are highly correlated (r = 96 %) and thus ASC can
      be used in place of either SI or DI in representing customer satisfaction scores.
      Also, these Kano model's customer satisfaction variables (SI, DI, and ASC) are
      each associated with self-stated requirements importance (IMP). Further analysis
      indicates that the value customers or users place on requirements that are met or
      on features that are incorporated into a product influences the level of
      satisfaction such customers derive from the product. The worth of a product
      feature is indicated by the perceived satisfaction customers get from the
      inclusion of such feature in the product design and development. The satisfaction
      users/customers derive when a requirement is fulfilled or when a feature is
      placed in the product (SI or ASC) is strongly influenced by the value the
      users/customers place on such requirements/features when met (IMP). However, the
      dissatisfaction users/customers received when a requirement is not met or when a
      feature is not incorporated into the product (DI), even though related to self
      stated requirements importance (IMP), does not have a strong effect on the
      importance/worth (IMP) of that given requirement/feature as perceived by the
      users or customers. Therefore, since customer satisfaction is proportionally
      related to the perceived requirements importance (worth), it is then necessary to
      give adequate attention to user/customer satisfying requirements (features) from
      elicitation to design and to the final implementation of the design.
      Incorporating user or customer satisfying requirements in product design is of
      great worth or value to the future users or customers of the product. 

PMID- 27026894
TI  - A numerical solution of a singular boundary value problem arising in boundary
      layer theory.
AB  - In this paper, a second-order nonlinear singular boundary value problem is
      presented, which is equivalent to the well-known Falkner-Skan equation. And the
      one-dimensional third-order boundary value problem on interval [Formula: see
      text] is equivalently transformed into a second-order boundary value problem on
      finite interval [Formula: see text]. The finite difference method is utilized to
      solve the singular boundary value problem, in which the amount of computational
      effort is significantly less than the other numerical methods. The numerical
      solutions obtained by the finite difference method are in agreement with those
      obtained by previous authors. 

PMID- 27026895
TI  - A numerical investigation of the GRLW equation using lumped Galerkin approach
      with cubic B-spline.
AB  - In this work, we construct the lumped Galerkin approach based on cubic B-splines
      to obtain the numerical solution of the generalized regularized long wave
      equation. Applying the von Neumann approximation, it is shown that the linearized
      algorithm is unconditionally stable. The presented method is implemented to three
      test problems including single solitary wave, interaction of two solitary waves
      and development of an undular bore. To prove the performance of the numerical
      scheme, the error norms [Formula: see text] and [Formula: see text] and the
      conservative quantities [Formula: see text], [Formula: see text] and [Formula:
      see text] are computed and the computational data are compared with the earlier
      works. In addition, the motion of solitary waves is described at different time
      levels. 

PMID- 27026896
TI  - Adaptive initial step size selection for Simultaneous Perturbation Stochastic
      Approximation.
AB  - A difficulty in using Simultaneous Perturbation Stochastics Approximation (SPSA)
      is its performance sensitivity to the step sizes chosen at the initial stage of
      the iteration. If the step size is too large, the solution estimate may fail to
      converge. The proposed adaptive stepping method automatically reduces the initial
      step size of the SPSA so that reduction of the objective function value occurs
      more reliably. Ten mathematical functions each with three different noise levels
      were used to empirically show the effectiveness of the proposed idea. A parameter
      estimation example of a nonlinear dynamical system is also included. 

PMID- 27026897
TI  - Is in vitro micrografting a possible valid alternative to traditional
      micropropagation in Cactaceae? Pelecyphora aselliformis as a case study.
AB  - Several taxa of Cactaceae are endangered by overcollection for commercial
      purposes, and most of the family is included in the Convention on International
      Trade in Endangered Species of Fauna and Flora (CITES). Micropropagation may play
      a key role to keep the pressure off wild populations and contribute to ex situ
      conservation of endangered taxa. One of the limits of micropropagation is the
      species-specific requirement of plant regulators for each taxon and sometimes
      even for different genotypes. With the micrografting technique the rootstock
      directly provides the scion with the necessary hormonal requirements. In this
      paper we present data on in vitro grafting of Pelecyphora aselliformis Ehrenberg,
      an Appendix I CITES listed species critically endangered and sought after by the
      horticultural trade, on micropropagated Opuntia ficus-indica Miller. Apical and
      sub-apical scions of P. aselliformis were used to perform micrografting with a
      successful rate of 97 and 81 % respectively. Survival rate after ex vivo transfer
      was 85 %. We hypothesize that this method could be applied to other endangered,
      slow growing taxa of Cactaceae thus contributing to the conservation of this
      endangered family. 

PMID- 27026898
TI  - The comparison of anterior knee pain in severe and non severe arthritis of the
      lateral facet of the patella following a mobile bearing unicompartmental knee
      arthroplasty.
AB  - In the past, medial osteoarthritis (OA) knee with symptomatic patellofemoral (PF)
      arthritis has not been recommended for a unicompartmental knee arthroplasty
      (UKA). However, recent studies have reported that UKA has shown good results in
      patients with medial OA of the knee, including those with PF arthritis. The
      purpose of this study is to compare the results between patients with medial OA
      knees; those with severe arthritis of the lateral facet of the patella and
      patients without severe arthritis of the lateral facet of the patella following
      mobile bearing UKA. We have prospectively evaluated 104 patients (114 knees) who
      had undergone an Oxford mobile bearing UKA. The mean follow-up was 19.05 months
      (range 12.30-29.70 months). The patients were divided into two groups: group I
      consisted of eighty patients (88 knees) who did not have severe arthritis of the
      lateral facet (Outerbridge grade 0-2) and group II had twenty-four patients (26
      knees) who had severe arthritis of the lateral facet (Outerbridge grade 3, 4). We
      recorded the incidence of anterior knee pain, knee scores, pain scores, and
      functional scores in comparison of the two groups. The visual analog scale (VAS)
      and incidence of post-operative anterior knee pain had not shown any significant
      differences. The VAS for post-operative anterior knee pain was 0.11 (SD 0.56,
      range 0-3 point) versus 0.12 (SD 0.59, range 0-3 point) for group I and group II
      patients, respectively (P = 0.98). The incidence of post-operative anterior knee
      pain was 4.5 versus 3.8 % for group I and group II patients, respectively (P =
      0.88). The pain scores and functional scores had not exhibited any differences.
      However, the knee scores of patients with severe arthritis of the lateral facet
      of the patella was worse than those seen in patients without severe arthritis of
      the lateral facet of the patella with a statistical significance. It was scored
      as 96.78 (SD 4.56, range 85-100) versus 94.43 (SD 4.50, range 81-100) for group I
      and group II patients, respectively (P = 0.02). Anterior knee pain, pain scores,
      and functional scores were not different between the two groups following a
      medial Oxford UKA. However, the knee scores of patients with severe arthritis of
      the lateral facet were worse than those in patients without severe arthritis of
      the lateral facet of the patella. 

PMID- 27026899
TI  - A dynamic approach to assess international competitiveness of Vietnam's garment
      and textile industry.
AB  - Garment and textile (G&T) industry has been playing as a driving force for the
      socio-economic development of Vietnam. With the international integration process
      and rising challenges from the global market, there is a need to examine
      international competitiveness of Vietnam's G&T industry to find out what Vietnam
      should focus on to enhance its position in the global market place. This paper,
      by using the Generalized Double Diamond Model (GDDM), analyzed international
      competitiveness of Vietnam's G&T industry and compared it with China. The results
      showed that Vietnam was less competitive than China in all four attributes of the
      GDDM. The lowest competitiveness of Vietnam in comparison with China was Related
      and Supporting industries, followed by Factor Conditions. Therefore, the paper
      argued that although Vietnam should improve all of the four attributes in the
      long term, Vietnam must put a high priority on developing Related and Supporting
      Industries and then enhance Factor Conditions while maintaining its strengths
      over China in terms of G&T export growths and favorable business context. 

PMID- 27026900
TI  - Impact of media coverage on the drinking dynamics in the scale-free network.
AB  - A binge drinking model with the impact of media in the scale-free network is
      proposed. The basic reproduction number [Formula: see text] is derived by the
      next generation matrix method. Stability of the alcohol free equilibrium is
      proved by the comparison theorem. Existence and uniqueness of the alcohol present
      equilibrium is also obtained. Furthermore, the permanence of the system and the
      influence of media coverage on the drinking dynamics are studied, and the
      difference between our model on heterogeneous and homogeneous networks is also
      discussed. Numerical simulations are presented to illustrate our theoretical
      results. Our results show that media coverage does not change the value of
      [Formula: see text] but it is an effective measure in reducing alcohol problems. 

PMID- 27026902
TI  - Impact response of a Timoshenko-type viscoelastic beam considering the extension
      of its middle surface.
AB  - In the present paper, the problem of low-velocity impact of an elastic sphere
      against a viscoelastic Timoshenko-type beam is studied considering the extension
      of its middle surface. The viscoelastic features of the beam out of the contact
      domain are governed by the standard linear solid model with derivatives of
      integer order, while within the contact domain the fractional derivative standard
      linear solid model is utilized, in so doing rheological constants of the material
      in both models are the same. However the presence of the additional parameter,
      i.e. fractional parameter which could vary from zero to unit, allows one to vary
      beam's viscosity, since the structure of the beam's material within this zone may
      be damaged, resulting in the decrease of the beam material viscosity in the
      contact zone. Consideration for transient waves (surfaces of strong
      discontinuity) propagating in the target out of the contact zone via the theory
      of discontinuities and determination of the desired values behind the surfaces of
      discontinuities upto the contact domain with the help of ray series, as well as
      the utilization of the Hertz theory in the contact zone allow one to obtain a set
      of two integro-differential equations, which govern the desired values, namely:
      the local bearing of the target and impactor's materials and the displacement of
      the beam within the contact domain. 

PMID- 27026901
TI  - Effect of saddle height on skin temperature measured in different days of
      cycling.
AB  - Infrared thermography can be useful to explore the effects of exercise on
      neuromuscular function. During cycling, it could be used to investigate the
      effects of saddle height on thermoregulation. The aim of this study was to
      examine whether different cycling postures, elicited by different knee flexion
      angles, could influence skin temperature. Furthermore, we also determined whether
      the reproducibility of thermal measurements in response to cycling differed in
      the body regions affected or not affected by saddle height. Sixteen cyclists
      participated in three tests of 45 min of cycling at their individual 50 % peak
      power output. Each test was performed in a different knee flexion position on the
      bicycle (20 degrees , 30 degrees , 40 degrees  knee flexion when the pedal crank
      was at 180 degrees ). Different knee angles were obtained by changing saddle
      height. Skin temperatures were determined by infrared thermography before,
      immediately after and 10 min after the cycling test, in 16 different regions of
      interest (ROI) in the trunk and lower limbs. Changes in saddle height did not
      result in changes in skin temperature in the ROI. However, lower knee flexion
      elicited higher temperature in popliteus after cycling than higher flexion (p =
      0.008 and ES = 0.8), and higher knee flexion elicited lower temperature variation
      in the tibialis anterior than intermediate knee flexion (p = 0.004 and ES = 0.8).
      Absolute temperatures obtained good and very good intraday reproducibility in the
      different measurements (ICCs between 0.44 and 0.85), but temperature variations
      showed lower reproducibility (ICCs between 0.11 and 0.74). Different postures
      assumed by the cyclist due to different saddle height did not influence
      temperature measurements. Skin temperature can be measured on different days with
      good repeatability, but temperature variations can be more sensitive to the
      effects of an intervention. 

PMID- 27026903
TI  - The enhanced recovery after surgery (ERAS) program in liver surgery: a meta
      analysis of randomized controlled trials.
AB  - The enhanced recovery after surgery (ERAS) program aims to attenuate the surgical
      stress response and decrease postoperative complications. It has increasingly
      replaced conventional approaches in surgical care. To evaluate the benefits and
      harms of the ERAS program compared to conventional care in patients undergoing
      liver surgery. We searched the MEDLINE, PubMed, EMBASE and Cochrane databases.
      All RCTs that compared the ERAS program with conventional care were selected.
      Four RCTs were eligible for analysis, which included 634 patients (309 ERAS vs.
      325 conventional). Overall morbidity (RR 0.67; 95 % CI 0.48-0.92; p = 0.01),
      primary length of stay (WMD -2.71; 95 % CI -3.43 to -1.99; p < 0.00001), total
      length of stay (WMD -2.10; 95 % CI -3.96 to -0.24; p = 0.03), time of functional
      recovery (WMD -2.30; 95 % CI -3.77 to -0.83; p = 0.002), and time to first flatus
      (SMD, -0.52; 95 % CI -0.69 to -0.35; p < 0.00001) were significantly shortened in
      the ERAS group. Quality of life was also better in the ERAS group. However, no
      significant differences were noted in mortality, readmission rates, operative
      time and intraoperative blood loss. The ERAS Program for liver surgery
      significantly reduced overall morbidity rates, accelerated functional recovery,
      and shortened the primary and total hospital stay without compromising
      readmission rates. Therefore, ERAS appears to be safe and effective. However, the
      conclusions are limited because of the low methodological quality of the analyzed
      studies. Further studies are needed to provide more solid evidence. 

PMID- 27026904
TI  - Application of the perturbation iteration method to boundary layer type problems.
AB  - The recently developed perturbation iteration method is applied to boundary layer
      type singular problems for the first time. As a preliminary work on the topic,
      the simplest algorithm of PIA(1,1) is employed in the calculations. Linear and
      nonlinear problems are solved to outline the basic ideas of the new solution
      technique. The inner and outer solutions are determined with the iteration
      algorithm and matched to construct a composite expansion valid within all parts
      of the domain. The solutions are contrasted with the available exact or numerical
      solutions. It is shown that the perturbation-iteration algorithm can be
      effectively used for solving boundary layer type problems. 

PMID- 27026905
TI  - Early atherosclerosis in normotensive patients with autosomal dominant polycystic
      kidney disease: the relation between epicardial adipose tissue thickness and
      carotid intima-media thickness.
AB  - Epicardial adipose tissue thickness (EATT) is suggested as a novel marker of
      subclinical atherosclerosis. Despite increased carotid intima-media thickness
      (CIMT) in autosomal dominant polycystic kidney disease (ADPKD) patients, the
      extent of the relationship between CIMT and EATT is unknown. The main purpose of
      our study was to evaluate the relation between EATT and CIMT in normotensive
      ADPKD patients with well-preserved renal function. Fifty-five normotensive ADPKD
      patients with normal renal function and 50 healthy control subjects were included
      in the study. EATT and CIMT were measured by echocardiography in all subjects.
      Correlation between EATT and CIMT was evaluated in ADPKD patients, while
      multivariate linear regression analysis was performed to determine factors
      predicting EATT and CIMT. ADPKD patients had significantly higher levels CIMT
      [0.7 (0.4-1.2) vs. 0.5 (0.4-0.8) mm, p < 0.001] and EATT (6.8 +/- 2.7 vs. 4.8 +/-
      1.2 mm, p < 0.001) as compared with control subjects. Significant positive
      correlation was found between EATT and CIMT (r = 0.58, p < 0.001). Higher CRP
      levels (OR 54.7, 95 % CI 37.44-72.01, p < 0.001) and having ADPKD (OR 10.2, 95 %
      CI 2.53-17.86, p = 0.01) were the only independent factors associated with a
      higher EATT. A higher age (OR 0.35, 95 % CI -0.02 to 0.71, p = 0.06) tended to be
      independently associated with a higher EATT. In conclusion, our findings suggest
      that EATT, being simply measured by echocardiography and correlated with CIMT,
      can be used to detect subclinical atherosclerosis in normotensive ADPKD patients.

PMID- 27026906
TI  - Late-Proterozoic to Paleozoic history of the peri-Gondwana Calabria-Peloritani
      Terrane inferred from a review of zircon chronology.
AB  - U-Pb analyses of zircon from ten samples of augen gneisses, eight mafic and
      intermediate metaigneous rocks and six metasediments from some tectonic domains
      along the Calabria-Peloritani Terrane (Southern Italy) contribute to knowledge of
      peri-Gondwanan evolution from Late-Proterozoic to Paleozoic times. All samples
      were equilibrated under amphibolite to granulite facies metamorphism during the
      Variscan orogeny. The zircon grains of all considered samples preserve a
      Proterozoic memory suggestive of detrital, metamorphic and igneous origin. The
      available data fit a frame involving: (1) Neoproterozoic detrital input from
      cratonic areas of Gondwana; (2) Pan-African/Cadomian assemblage of blocks derived
      from East and West African Craton; (3) metamorphism and bimodal magmatism between
      535 and 579 Ma, within an active margin setting; (4) rifting and opening of
      Ordovician basins fed by detrital input from the assembled Cadomian blocks. The
      Paleozoic basins evolved through sedimentation, metamorphism and magmatism during
      the Variscan orogeny involving Palaeozoic and pre-Paleozoic blocks. The
      Proterozoic zircon records decidedly decrease in the high grade metamorphic rocks
      affected by Variscan pervasive partial melting. 

PMID- 27026907
TI  - Spontaneous adverse drug reaction reporting by patients in Canada: a multi-method
      study-study protocol.
AB  - BACKGROUND: Monitoring adverse drug reactions (ADRs) through pharmacovigilance
      are vital to patient safety. Spontaneous ADR reporting is one method of
      pharmacovigilance, and in Canada all reporter types admitted to report an ADR to
      the Canadian Vigilance Program at Health Canada. Reports are submitted to Health
      Canada by post, telephone, or via the internet. The Canada Vigilance Program
      electronically records submitted information to detect medication safety alerts.
      Although previous studies have shown differences between patients and healthcare
      professionals (HCPs) on the types of drugs and reactions reported, relatively
      little is known about the importance of patient reports to pharmacovigilance
      activities. This article proposed a multi-method approach to evaluate the
      importance of patient ADR reporting on pharmacovigilance activities, by
      systematically review the available literature, comparing patient-versus HCPs
      generated ADR reports that were submitted to the Canada Vigilance Program, and
      exploring patient views and experiences regarding the Canadian ADR reporting
      system. METHODS: Guided by a risk-perception theoretical lens, the proposed multi
      methods research study will involve three phases. Phase I is a systematic review
      of all studies that analyse the factors influence ADR reporting by patients to
      the pharmacovigilance schemes. Phase II is a descriptive statistical analysis of
      all ADR reports received by the Canada Vigilance Program database between 1
      January 2000 and 31 December 2014 from patients and HCPs to compare ADRs reported
      by patients with those reported by HCP reports in terms of ADR seriousness, ADR
      classification by system organ class, and the medication involved based on the
      anatomical therapeutic class system. In phase III, an interpretative descriptive
      approach will be used to explore patient's views and experiences on ADR reporting
      and usability of the Canadian Vigilance ADR report. Participants will be
      purposefully selected to ensure diverse backgrounds and experiences. Interviews
      will be digitally-recorded, transcribed verbatim, and inductively analysed to
      identify themes. Patients will be interviewed until theoretical saturation is
      achieved. DISCUSSION: Findings from this research will highlight the role of the
      patients in directly reporting ADRs, and provide information that may guide
      streamline and optimizing patient ADR reporting. Policy makers, public health
      officials, and regulatory agencies will require this critical information in
      order to improve medication safety in Canada and worldwide.

PMID- 27026908
TI  - Use of electrochemically activated aqueous solutions in the manufacture of fur
      materials.
AB  - The influence of characteristics of electrochemically activated aqueous
      processing mediums in the treatment of fur skins with different contents of fatty
      substances was investigated. The use of electroactive water, namely anolytes and
      catholytes, forgoing antiseptics or surface-active materials, helped to restore
      the hydration of fur skins and to remove from them soluble proteins,
      carbohydrates and fatty substances. The activating effect of anolyte and
      catholyte in solutions of water on the processes of treating raw furs is
      explained by their special physical and chemical properties, namely the presence
      of free radicals, ions and molecules of water which easily penetrate cells'
      membranes and into the structure of non-collagen components and microfiber
      structure of dermic collagen. The stage of lengthy acid and salt treatment is
      excluded from the technical treatment as a result of using electroactivated water
      with high oxidizing power. A low-cost technology of processing different kinds of
      fur with the use of electroactivated water provides for substantial economy of
      water and chemical reagents, a two to threefold acceleration of the soaking and
      tanning processes and creation of highly elastic fur materials with a specified
      set of physical and chemical properties. At the same time the technology of
      preparatory processes of fur treatment excludes the use of such toxic antiseptics
      as formalin and sodium silicofluoride, which gives grounds to regard it as
      ecologically safe. 

PMID- 27026909
TI  - Ethyl pyruvate attenuated coxsackievirus B3-induced acute viral myocarditis by
      suppression of HMGB1/RAGE/NF-KappaB pathway.
AB  - Inflammation plays important roles in the pathogenesis of coxsackievirus B3
      (CVB3)-induced acute viral myocarditis (AVMC). Ethyl pyruvate (EP) has been shown
      to be an anti-inflammatory agent. High mobility group box 1 (HMGB1)/receptor for
      advanced glycation end product (RAGE)/nuclear factor (NF)-KappaB pathway has
      close relation with inflammatory responses. Here, we investigated the effects of
      EP on CVB3-induced AVMC and potential mechanisms. The mice with AVMC were treated
      with EP (40 or 80 mg/kg/day) from day 5 to day 7 post-infection. EP significantly
      decreased the mortality of mice with AVMC. H&E staining and immunohistochemistry
      for HMGB1 demonstrated less inflammatory lesions and fewer abnormal location of
      HMGB1 in the hearts of AVMC mice receiving EP. Immuoblot showed that EP
      significantly inhibited the levels of HMGB1, RAGE, phospho(p)-NF-KappaB and p-I
      KappaBalpha, and raised I-KappaBalpha expression in the hearts of AVMC mice.
      Furthermore, real-time PCR and Elisa displayed decreased levels of HMGB1, TNF
      alpha, IL-1beta, IL-17 and increased levels of IL-10 in the hearts and serum of
      AVMC mice treated with EP. Our findings suggest that EP protects against CVB3
      induced AVMC that is associated with inhibition of HMGB1/RAGE/NF-KappaB pathway. 

PMID- 27026910
TI  - The hepatocurative effects of Cynara scolymus L. leaf extract on carbon
      tetrachloride-induced oxidative stress and hepatic injury in rats.
AB  - Cynara scolymus is a pharmacologically important medicinal plant containing
      phenolic acids and flavonoids. Experimental studies indicate antioxidant and
      hepatoprotective effects of C. scolymus but there have been no studies about
      therapeutic effects of liver diseases yet. In the present study, hepatocurative
      effects of C. scolymus leaf extract on carbon tetrachloride (CCl4)-induced
      oxidative stress and hepatic injury in rats were investigated by serum hepatic
      enzyme levels, oxidative stress indicator (malondialdehyde-MDA), endogenous
      antioxidants, DNA fragmentation, p53, caspase 3 and histopathology. Animals were
      divided into six groups: control, olive oil, CCl4, C. scolymus leaf extract,
      recovery and curative. CCl4 was administered at a dose of 0.2 mL/kg twice daily
      on CCl4, recovery and curative groups. Cynara scolymus extract was given orally
      for 2 weeks at a dose of 1.5 g/kg after CCl4 application on the curative group.
      Significant decrease of serum alanine-aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels were determined in the curative group. MDA levels
      were significantly lower in the curative group. Significant increase of
      superoxide dismutase (SOD) and catalase (CAT) activity in the curative group was
      determined. In the curative group, C. scolymus leaf extract application caused
      the DNA % fragmentation, p53 and caspase 3 levels of liver tissues towards the
      normal range. Our results indicated that C. scolymus leaf extract has
      hepatocurative effects of on CCl4-induced oxidative stress and hepatic injury by
      reducing lipid peroxidation, providing affected antioxidant systems towards the
      normal range. It also had positive effects on the pathway of the regulatory
      mechanism allowing repair of DNA damage on CCl4-induced hepatotoxicity. 

PMID- 27026911
TI  - Fixed point theorems on multi valued mappings in b-metric spaces.
AB  - In this paper, we prove a fixed point theorem and a common fixed point theorem
      for multi valued mappings in complete b-metric spaces. 

PMID- 27026912
TI  - Convergence in [Formula: see text]-quasicontinuous posets.
AB  - In this paper, we present one way to generalize [Formula: see text]-convergence
      and [Formula: see text]-convergence of nets for arbitrary posets by use of the
      cut operator instead of joins. Some convergence theoretical characterizations of
      [Formula: see text]-continuity and [Formula: see text]-quasicontinuity of posets
      are given. The main results are: (1) a poset P is [Formula: see text]-continuous
      if and only if the [Formula: see text]-convergence in P is topological; (2) P is
      [Formula: see text]-quasicontinuous if and only if the [Formula: see text]
      convergence in P is topological. 

PMID- 27026913
TI  - Comparison of ablation defect on MR imaging with computer simulation estimated
      treatment zone following irreversible electroporation of patient prostate.
AB  - To determine whether patient specific numerical simulations of irreversible
      electroporation (IRE) of the prostate correlates with the treatment effect seen
      on follow-up MR imaging. Computer models were created using intra-operative US
      images, post-treatment follow-up MR images and clinical data from six patients
      receiving IRE. Isoelectric contours drawn using simulation results were compared
      with MR imaging to estimate the energy threshold separating treated and untreated
      tissue. Simulation estimates of injury to the neurovascular bundle and rectum
      were compared with clinical follow-up and patient reported outcomes. At the
      electric field strength of 700 V/cm, simulation estimated electric field
      distribution was not different from the ablation defect seen on follow-up MR
      imaging (p = 0.43). Simulation predicted cross sectional area of treatment (mean
      532.33 +/- 142.32 mm(2)) corresponded well with the treatment zone seen on MR
      imaging (mean 540.16 +/- 237.13 mm(2)). Simulation results did not suggest injury
      to the rectum or neurovascular bundle, matching clinical follow-up at 3 months.
      Computer simulation estimated zone of irreversible electroporation in the
      prostate at 700 V/cm was comparable to measurements made on follow-up MR imaging.
      Numerical simulation may aid treatment planning for irreversible electroporation
      of the prostate in patients. 

PMID- 27026914
TI  - Fully automated tracking of cardiac structures using radiopaque markers and high
      frequency videofluoroscopy in an in vivo ovine model: from three-dimensional
      marker coordinates to quantitative analyses.
AB  - PURPOSE: Recently, algorithms were developed to track radiopaque markers in the
      heart fully automated. However, the methodology did not allow to assign the exact
      anatomical location to each marker. In this case study we describe the steps from
      the generation of three-dimensional marker coordinates to quantitative data
      analyses in an in vivo ovine model. METHODS: In one adult sheep, twenty silver
      balls were sutured to the right side of the heart: 10 to the tricuspid annulus,
      one to the anterior tricuspid leaflet and nine to the epicardial surface of the
      right ventricle. In addition, 13 cylindrical tantalum markers were implanted into
      the left ventricle. Data were acquired with a biplanar X-ray acquisition system
      (Neurostar R, Siemens AG, 500 Hz). Radiopaque marker coordinates were determined
      fully automated using novel tracking algorithms. RESULTS: The anatomical marker
      locations were identified using a 3-dimensional model of a single frame
      containing all tracked markers. First, cylindrical markers were manually
      separated from spherical markers, thus allowing to distinguish right from left
      heart markers. The fast moving leaflet marker was identified by using video loops
      constructed of all recorded frames. Rotation of the 3-dimensional model allowed
      the identification of the precise anatomical position for each marker. Data sets
      were then analyzed quantitatively using customized software. CONCLUSIONS: The
      method presented in this case study allowed quantitative data analyses of
      radiopaque cardiac markers that were tracked fully automated with high temporal
      resolution. However, marker identification still requires substantial manual
      work. Future improvements including the implication of marker identification
      algorithms and data analysis software could allow almost real-time quantitative
      analyses of distinct cardiac structures with high temporal and spatial
      resolution.

PMID- 27026915
TI  - The F-coindex of some graph operations.
AB  - The F-index of a graph is defined as the sum of cubes of the vertex degrees of
      the graph. In this paper, we introduce a new invariant which is named as F
      coindex. Here, we study basic mathematical properties and the behavior of the
      newly introduced F-coindex under several graph operations such as union, join,
      Cartesian product, composition, tensor product, strong product, corona product,
      disjunction, symmetric difference of graphs and hence apply our results to find
      the F-coindex of different chemically interesting molecular graphs and nano
      structures. 

PMID- 27026917
TI  - Male and female Ethiopian and Kenyan runners are the fastest and the youngest in
      both half and full marathon.
AB  - In major marathon races such as the 'World Marathon Majors', female and male East
      African runners particularly from Ethiopia and Kenya are the fastest. However,
      whether this trend appears for female and male Ethiopians and Kenyans at
      recreational level runners (i.e. races at national level) and in shorter road
      races (e.g. in half-marathon races) has not been studied yet. Thus, the aim of
      the present study was to examine differences in the performance and the age of
      female and male runners from East Africa (i.e. Ethiopians and Kenyans) between
      half- and full marathons. Data from 508,108 athletes (125,894 female and 328,430
      male half-marathoners and 10,205 female and 43,489 male marathoners) originating
      from 126 countries and competing between 1999 and 2014 in all road-based half
      marathons and marathons held in one country (Switzerland) were analysed using Chi
      square (chi(2)) tests, mixed-effects regression analyses and one-way analyses of
      variance. In half-marathons, 48 women (0.038 %) and 63 men (0.019 %) were from
      Ethiopia and 80 women (0.063 %) and 134 men (0.040 %) from Kenya. In marathons,
      three women (0.029 %) and 15 men (0.034 %) were from Ethiopia and two women
      (0.019 %) and 33 men (0.075 %) from Kenya. There was no statistically significant
      association between the nationality of East Africans and the format of a race. In
      both women and men, the fastest race times in half-marathons and marathons were
      achieved by East African runners (p < 0.001). Ethiopian and Kenyan runners were
      the youngest in both sexes and formats of race (p < 0.001). In summary, women and
      men from Ethiopia and Kenya, despite they accounted for <0.1 % in half-marathons
      and marathons, achieved the fastest race times and were the youngest in both half
      marathons and marathons. These findings confirmed in the case of half-marathon
      the trend previously observed in marathon races for a better performance and a
      younger age in East African runners from Ethiopia and Kenya. 

PMID- 27026918
TI  - Existence and global exponential stability of periodic solutions for n
      dimensional neutral dynamic equations on time scales.
AB  - In this paper, by using the existence of the exponential dichotomy of linear
      dynamic equations on time scales and the theory of calculus on time scales, we
      study the existence and global exponential stability of periodic solutions for a
      class of n-dimensional neutral dynamic equations on time scales. We also present
      an example to illustrate the feasibility of our results. The results of this
      paper are completely new and complementary to the previously known results even
      in both the case of differential equations (time scale [Formula: see text]) and
      the case of difference equations (time scale [Formula: see text]). 

PMID- 27026919
TI  - What differs between happy and unhappy people?
AB  - This study explores the determinants (demographic, personal, behavioural, and
      social) by which happy and unhappy people differ. The primary sample from which
      the participants were chosen was a representative sample of Croatian citizens (N
      = 4000). On the basis of the distribution of overall happiness the sample of the
      highest (the happy group) and the lowest 10 % of participants (the unhappy group)
      were selected. The happy group (N = 400) represented the upper end of the
      happiness distribution, while the unhappy group (N = 400) represented the lower
      end of the distribution. The questionnaire included demographic characteristics
      (age, gender, income, and education), ratings of subjective health status,
      satisfaction with specific personal and national domains (IWI-International
      Wellbeing Index), trust in people, and trust in institutions. Frequency of
      various leisure activities, and involvement in the community life were also
      reported. The differences in examined variables were analysed between the two
      groups. Results showed that the happy individuals were younger, with higher
      income, and with higher education than unhappy ones. After controlling for age,
      income, and education level, the happy people were found to be more satisfied
      with personal and national wellbeing domains, of better subjective health status,
      reported higher trust in people and institutions, and were more engaged in
      leisure activities and community life than the unhappy ones. 

PMID- 27026916
TI  - Single nucleotide polymorphisms of HSP90AA1 gene influence response of SLE
      patients to glucocorticoids treatment.
AB  - Heat shock protein 90 (HSP90) is an important glucocorticoid receptor (GR)
      chaperone protein, and is supposed to be the key factor in regulating
      glucocorticoids (GCs) effects. The aim of the present study was to explore
      whether single nucleotide polymorphisms (SNPs) within HSP90AA1 gene affect the
      response of systemic lupus erythematosus (SLE) patients to GCs treatment. Two
      hundred and forty-five SLE patients were treated with GCs (prednisone) for 12
      weeks. SLE disease activity index (SLEDAI) was used to assess the response of SLE
      patients to GCs treatment, and patients were classified into sensitive group and
      insensitive group. HapMap database and Haploview software were used to select tag
      SNPs. Tag SNPs were genotyped by using multiplex SNaPshot method. Univariate and
      multivariate logistic regression analyses were used to discriminate the impact of
      SNPs of HSP90AA1 gene on the response of SLE patients to GCs treatment. Two
      hundred and thirty three SLE patients finished the 12-week follow-up. Of these
      patients, 128 patients were included in sensitive group, and 105 patients were
      included in insensitive group. Seven tag SNPs were selected within HSP90AA1 gene.
      We detected significant associations for rs7160651 (dominant model: crude OR
      0.514, 95 % CI 0.297-0.890, P = 0.018; adjusted OR 0.518, 95 % CI 0.293-0.916, P
      = 0.024), rs10873531 (dominant model: crude OR 0.516, 95 % CI 0.305-0.876, P =
      0.014; adjusted OR 0.522, 95 % CI 0.304-0.898, P = 0.019) and rs2298877 (dominant
      model: crude OR 0.543, 95 % CI 0.317-0.928, P = 0.026, adjusted OR 0.558, 95 % CI
      0.323-0.967, P = 0.037) polymorphisms, but not for other polymorphisms (P >
      0.05). The present study demonstrates that HSP90AA1 gene SNPs may affect the
      response of SLE patients to GCs treatment. 

PMID- 27026920
TI  - Simulation of a computed HbA1c using a weighted average glucose.
AB  - BACKGROUND: The A1c-derived average glucose examined the link between the
      glycated haemoglobin and the estimated average glucose, and provided a linear
      relation between them. Other studies proved that, over a period of 4 months,
      plasma glucose in the preceding 30 days contribute to about 50 % to the glycated
      haemoglobin value while the other 50 % is due to the remaining 3 months
      altogether. TECHNICAL DETAILS OF THE METHOD: In this technical note, we propose a
      weighted method assuming that the contribution of glucose to glycated haemoglobin
      over 3 months is chronologically 20 %, 30 % and 50 % respectively. A comparison
      is made with the linear regression method which uses the same estimated average
      glucose over the whole period. Results yielded by the weighted method are also
      compared to those given by the model proposed by Ladyzynski et al. FINDINGS: A
      simulation is carried out on data assumed to come from a first individual with
      nearly the same level of glucose over 3 months, a second individual who starts
      with high levels of glucose and then reaches a stabilised low level by the last
      month, and finally, a third case who had just been diagnosed with diabetes during
      the last month whereas he/she had a normal glycaemia during the preceding 2
      months. The weighted method gives more realistic values of HbA1c (7.36 %, 6.80 %,
      8.49 %) than the linear regression method without weights which gives the same
      value (7.45 %) for the three cases. Another comparison shows that the three
      values given by the weighted method are slightly smaller than the corresponding
      values given by the model of Ladyzynski et al. (7.62 %, 7.02 %, 8.8 %) but the
      relative variation is nearly the same for the three values (~3 %). CONCLUSSION:
      Without regular self-testing and day-to-day insights, a sole HbA1c value can be
      confusing and misleading. For physicians and patients, a clear understanding of
      the relationship between the weighted average glucose and HbA1c is necessary in
      order to set an appropriate daily control depending on whether the glucose is
      stabilized over the whole period, at the beginning, at the end; or still under
      recurrent episodes of high and low levels. The measured HbA1c at a biological
      laboratory gives no indication on glucose variation. Moreover, low values of
      glucose may cancel high values and lead to a "good" average glucose and ideal
      glycated haemoglobin.

PMID- 27026921
TI  - Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive
      tract and gastrointestinal cancers: a meta-analysis.
AB  - Cancers of the upper aero-digestive and gastrointestinal tract are one of the
      major causes of mortality around the world. DNA repair genes play a vital role in
      preventing carcinogenesis by maintaining genomic integrity. Polymorphisms in the
      nucleotide sequence of DNA repair genes are often reported to be associated with
      an increased risk for different cancers. The OGG1 gene encodes the enzyme 8
      oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA.
      Several studies report that the OGG1 Ser326Cys polymorphism increases the risk
      for cancers of the upper aero-digestive and gastrointestinal tract. However,
      other studies provide evidence that such an association does not exist. A meta
      analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the
      upper aero-digestive and gastrointestinal tract was therefore undertaken in order
      to resolve this ambiguity. Seventeen studies were recruited for this meta
      analysis after screening 58 articles with a total of 5533 cases and 6834 controls
      for which the odds ratio with 95 % confidence interval was calculated. Begg's
      funnel test and Egger's test were performed for calculating publication bias. Our
      study reveals an association between OGG1 Ser326Cys polymorphism and cancer
      susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs
      CC; odds ratio, OR 1.22; 95 % CI 1.05-1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09
      1.70; GG vs CC; OR 1.46; 95 % CI 1.12-1.92). Subgroup analysis based on cancer
      types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism
      to the risk for upper aero-digestive and gastrointestinal tract cancers among
      both the Asian and the Caucasian populations. No risk was however observed for
      smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys
      polymorphism may be associated with the increased risk for aero-digestive tract
      and gastro-intestinal cancers in both Asian and Caucasian populations. 

PMID- 27026922
TI  - Habitat preferences and conservation threats to Black-necked Cranes wintering in
      Bhutan.
AB  - Black-necked Crane (Grus nigricollis) is a vulnerable Red list species whose
      populations are declining. However, little is known about Black-necked Cranes'
      habitat requirements or the causes of their population decline. We identified
      Black-necked Cranes' winter roost and foraging preferences of Black-necked Cranes
      in Bhutan during the winter of 2013-2014. Black-necked Cranes' roosts were
      recorded using Garmin GPSmap 60CSx, while foraging preferences and threats to the
      birds were identified based on a survey of household heads (n = 107) residing
      within a 3 km radius of roost sites. We grouped the threats identified by the
      communities into four major categories, viz. biological, social, political and
      natural threats based on the relevance. Of the four major threats, communities
      residing within the roosting and foraging habitat of the Black-necked Crane
      reported biological threat as major. Biological threats as reported by
      communities include loss of habitat, food shortage and competition from other
      animals. We recommend the present roosting areas be designated as part of the
      conservation areas for Black-necked Crane wintering in Bumthang district. In
      addition to preserving these areas, government should also encourage farming in
      foraging habitats of Black-necked Crane, because they mainly feed on barley,
      wheat, paddy, potatoes and buckwheat, besides roots, tubers and insects in the
      wetlands. 

PMID- 27026924
TI  - Violent repression of environmental protests.
AB  - As global sea levels and natural resource demands rise, people around the world
      are increasingly protesting environmental threats to their lives and livelihoods.
      What are the conditions under which these peaceful environmental protests are
      violently repressed? This paper uses the random forest algorithm to conduct an
      event analysis of grassroots environmental protests around the world. Utilizing a
      database of 175 grassroots environmental protests, we found that: (1) a large
      proportion (37 %) of the protests involved violent repression; (2) most of the
      violence (56 %) was directed against marginalized groups; and (3) violence was
      geographically concentrated the global south in Latin America and Asia. The
      primary predictors of violence were political empowerment, GDP per capita,
      industry type, the presence of marginalized groups, and geographic region. Our
      analysis reveals a complex relationship between governance, resource extraction,
      and international funding that often resulted in human rights violations against
      marginalized groups. 

PMID- 27026923
TI  - Review of evolving etiologies, implications and treatment strategies for the
      superior vena cava syndrome.
AB  - Superior vena cava syndrome (SVCS) is a relatively common sequela of mediastinal
      malignancies and may cause significant patient distress. SVCS is a medical
      emergency if associated with laryngeal or cerebral edema. The etiologies and
      management of SVCS have evolved over time. Non-malignant SVCS is typically caused
      by infectious etiologies or by thrombus in the superior vena cava and can be
      managed with antibiotics or anti-coagulation therapy, respectively. Radiation
      therapy (RT) has long been a mainstay of treatment of malignant SVCS.
      Chemotherapy has also been used to manage SVCS. In the past 20 years,
      percutaneous stenting of the superior vena cava has emerged as a viable option
      for SVCS symptom palliation. RT and chemotherapy are still the only modalities
      that can provide curative treatment for underlying malignant etiologies of SVCS.
      The first experiences with treating SVCS with RT were reported in the 1970's, and
      several advances in RT delivery have subsequently occurred. Hypo-fractionated RT
      has the potential to be a more convenient therapy for patients and may provide
      equal or superior control of underlying malignancies. RT may be combined with
      stenting and/or chemotherapy to provide both immediate symptom palliation and
      long-term disease control. Clinicians should tailor therapy on a case-by-case
      basis. Multi-disciplinary care will maximize treatment expediency and efficacy. 

PMID- 27026926
TI  - Levels of heavy metals in the raw and processed Ethiopian tobacco leaves.
AB  - Tobacco (Nicotiana tabacum L.) is a commercial plant. Tobacco leaves naturally
      accumulate and concentrate relatively high levels of heavy metals and particular
      cadmium in leaves. Tobacco is one of the basic agricultural products, in
      Ethiopia, with social and economic importance. However, there is no report in the
      literature on the determination of levels of heavy metals in Ethiopian tobacco
      leaves. Hence this research is intended to determine the levels of heavy metals
      in the raw and processed Ethiopian Virginia tobacco leaves. Samples of raw
      Virginia tobacco leaves were collected from two different regions of Ethiopia
      (Billate and Shewa Robit). The three processed tobacco samples were collected
      from National Tobacco Enterprise, Addis Ababa, Ethiopia. The samples were wet
      digested using 3 mL HNO3 (69-72 %) and 3 mL HClO4 (70 %) at 350  degrees C for
      3.5 h and concentrations of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) in the
      samples were determined by flame atomic absorption spectrometer. The mean metals
      concentrations (in ug/g dry weight) in the raw Virginia tobacco leaves from
      Billate and Shewa Robit, respectively, were: Cu (4.38, 7.30), Zn (53.7, 33.2), Cd
      (1.20, 1.30), Cr (ND, 1.45), Ni (ND, 1.90). The mean metals concentrations (in
      ug/g dry weight) in the processed tobacco from Billate and Shewa Robit,
      respectively, were: Cu (9.80, 12.8), Ni (2.35, 2.20) Cd (1.45, 1.90), Cr (1.65,
      1.75), Zn (101, 83.8). The mean metals concentrations (in ug/g dry weight) in the
      processed tobacco Nyala (Ethiopian cigarette leaves) were: Cu (8.95), Cd (1.55),
      Cr (1.62), Ni (4.70), Zn (79.3). The concentrations of Cr and Ni in tobacco
      leaves from Billate and Pb in all the tobacco samples were below the detection
      limits. This study showed that the metal contents of tobacco leaves varied with
      the geographical origin in which the tobacco plant grows. The metal contents of
      processed tobacco were higher than the corresponding raw leaves. Pb was not
      detected in both the raw and processed Ethiopian tobacco leaves. 

PMID- 27026925
TI  - Plasma level of advanced oxidation protein products as a novel biomarker of acute
      lung injury following cardiac surgery.
AB  - This study was designed to test the hypothesis that whether the plasma level of
      advanced oxidant protein products (AOPPs) would be useful for the clinical
      diagnosis of acute lung injury (ALI) following cardiac surgery with the technique
      of cardiopulmonary bypass (CPB). In this prospective study, seventy consecutive
      adults undergoing open heart surgery with CPB were included and assigned into the
      ALI (n = 18) and non-ALI (n = 52) groups according to the American-European
      Consensus Criteria. Plasma concentrations of AOPPs were measured at baseline,
      postoperative 1 h, 12 h, 24 h, and 48 h. Eighteen patients (25.7 %) developed ALI
      after surgery. The plasma levels of AOPPs in the ALI group were significantly
      increased and remained considerably higher at all time points after operation
      (all P < 0.05). Multivariate logistic regression analysis revealed that the
      plasma level of AOPPs at 1 h after operation was an independent predictor for the
      diagnosis of ALI (OR 1.164; 95 % CI 1.068-1.269; P = 0.001). Plasma level of
      AOPPs could serve as an early biomarker of the incidence of ALI in adult patients
      who underwent open cardiac surgery with the technique of CPB. 

PMID- 27026927
TI  - psi-Contraction and [Formula: see text]-contraction in Menger probabilistic
      metric space.
AB  - The purpose of this paper is to present the definition of [Formula: see text]
      contractive mapping and to discuss the relation of [Formula: see text]
      contractive mappings and [Formula: see text]-contractive mappings. Furthermore,
      the generalized [Formula: see text]-contraction mapping principle has been proved
      without the uniqueness condition. Meanwhile, the generalized [Formula: see text]
      contraction mapping principle has been obtained by using an ingenious method. 

PMID- 27026928
TI  - Effects of cardioactive drugs on human induced pluripotent stem cell derived long
      QT syndrome cardiomyocytes.
AB  - Human induced pluripotent stem cells (hiPSC) have enabled a major step forward in
      pathophysiologic studies of inherited diseases and may also prove to be valuable
      in in vitro drug testing. Long QT syndrome (LQTS), characterized by prolonged
      cardiac repolarization and risk of sudden death, may be inherited or result from
      adverse drug effects. Using a microelectrode array platform, we investigated the
      effects of six different drugs on the electrophysiological characteristics of
      human embryonic stem cell-derived cardiomyocytes as well as hiPSC-derived
      cardiomyocytes from control subjects and from patients with type 1 (LQT1) and
      type 2 (LQT2) of LQTS. At baseline the repolarization time was significantly
      longer in LQTS cells compared to controls. Isoprenaline increased the beating
      rate of all cell lines by 10-73 % but did not show any arrhythmic effects in any
      cell type. Different QT-interval prolonging drugs caused prolongation of cardiac
      repolarization by 3-13 % (cisapride), 10-20 % (erythromycin), 8-23 % (sotalol),
      16-42 % (quinidine) and 12-27 % (E-4031), but we did not find any systematic
      differences in sensitivity between the control, LQT1 and LQT2 cell lines.
      Sotalol, quinidine and E-4031 also caused arrhythmic beats and beating arrests in
      some cases. In summary, the drug effects on these patient-specific cardiomyocytes
      appear to recapitulate clinical observations and provide further evidence that
      these cells can be applied for in vitro drug testing to probe their vulnerability
      to arrhythmia. 

PMID- 27026929
TI  - Sulforaphane induces apoptosis and inhibits invasion in U251MG glioblastoma
      cells.
AB  - In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant
      and anti-tumor activities. In the present study, the viability inhibition effects
      of SFN in U251MG glioblastoma cells were analyzed by MTS. Morphology changes were
      observed by microscope. Apoptotic effects of SFN were evaluated by annexin V
      binding capacity with flow cytometric analysis. Invasion inhibition effects of
      SFN were tested by the invasion assay. The molecular mechanisms of apoptotic
      effects and invasion inhibition effects of SFN were detected by western blot and
      gelatin zymography. The results indicated that SFN has potent apoptotic effects
      and invasion inhibition effects against U251MG glioblastoma cells. These effects
      are both dose dependent. Taken together, SFN possessed apoptotic activity on
      U251MG cells indicated by increased annexin V-binding capacity, Bad, Bax,
      cytochrome C expression, and decreased Bcl-2 and survivin expressions. SFN
      inhibited invasion in U251MG cells via upregulation of E-cadherin and
      downregulation of MMP-2, MMP-9 and Galectin-3. 

PMID- 27026930
TI  - Is PET-CT an accurate method for the differential diagnosis between chondroma and
      chondrosarcoma?
AB  - The differential diagnosis between chondroma and intraosseous chondrosarcoma is
      based on imaging and clinical exams, but only a biopsy can confirm diagnosis. The
      aim of this study was to evaluate the value of PET-CT in differentially
      diagnosing chondroma and chondrosarcoma. From October 2009 to May 2015, 36
      patients with cartilaginous bone lesions in the extremities, 12 (33.3 %) men and
      24 (66.6 %) women, were prospectively included in the study. Patients ranged in
      age from 21 to 68 years, with a mean age of 44 years. Lesions were located in the
      long bones: in the proximal humerus in 26 (72.2 %) patients, in the femoral shaft
      in 1 (2.7 %), in the distal femur in 7 (19.4 %), and in the proximal tibia in 2
      (5.5 %). The SUVmax value of 2.0 was used to separate between patients submitted
      to surgery and patients submitted to observation. Among the 36 patients studied,
      17 (47.2 %) had SUVmax <= 2.0, and they were diagnosed as chondroma and they were
      treated conservatively. Follow-up ranged from 14 to 76 months, averaging 38
      months. Nineteen (52.7 %) patients with SUVmax >2.0 were diagnosed as
      chondrosarcoma and underwent surgery. The area of the curve, calculated
      considering the SUV variable as numeric, is estimated in 0.966, with a 95 %
      confidence interval from 0.906 to 1.000. To evaluate the sensitivity, specificity
      and positive/negative predictive values, it was built a 2 * 2 table. Significance
      was set at p < 0.05. According the criteria of maximum sensitivity and
      specificity, the cut point suggested to SUVmax was 2.2. If we consider this
      point, it is possible to identify 19 of 36 positive cases to chondroma (52.8 %),
      it means, all chondrosarcomas of the series. We concluded that PET-CT can be used
      as an objective and quantitative method of differentiating between chondromas and
      chondrosarcomas located within the long bones. It represents a complementary
      examination to standard imaging (X-ray, scintigraphy, CT and MRI) and
      pathological exams. The SUVmax between 2.0 and 2.2 would be a range area between
      chondroma and chondrosarcoma and this range can be of value, among others exams,
      in decide the best treatment for patients with cartilaginous lesions in long
      bones. Level of evidence Level I-diagnostic study-prospectively investigating a
      diagnostic test using a universally applied "gold" standard. 

PMID- 27026931
TI  - School failure in students who are normal-hearing or deaf: with or without
      cochlear implants.
AB  - To evaluate the impact of cochlear implants on the school failure of deaf who
      attend mainstream classes by comparing them to their normal-hearing peers as well
      as deaf without cochlear implants. This case-control study included participants
      aged 8-18 years. The number of school years failed was obtained from school
      records. The greatest differences in achievement levels were found between
      hearing students and those who were deaf without cochlear implants. Cochlear
      implants provide educational opportunities for hearing-impaired students, yet
      those without cochlear implants remain at a great disadvantage. These findings
      suggest that measures promoting greater equity and quality for all deaf students
      allow achievement levels closer to those of the not impaired. 

PMID- 27026932
TI  - Causes and remedies for the dominant risk factors in Enterprise System
      implementation projects: the consultants' perspective.
AB  - The purpose of this research was to investigate the causes of the dominant risk
      factors, affecting Enterprise System implementation projects and propose remedies
      for those risk factors from the perspective of implementation consultants. The
      study used a qualitative research strategy, based on e-mail interviews, semi
      structured personal interviews with consultants and participant observation
      during implementation projects. The main contribution of this paper is that it
      offers viable indications of how to mitigate the dominant risk factors. These
      indications were grouped into the following categories: stable project scope,
      smooth communication supported by the project management, dedicated, competent
      and decision-making client team, competent and engaged consultant project
      manager, schedule and budget consistent with the project scope, use of
      methodology and procedures, enforced and enabled by the project managers,
      competent and dedicated consultants. A detailed description is provided for each
      category. 

PMID- 27026933
TI  - Intelligent emission-sensitive routing for plugin hybrid electric vehicles.
AB  - The existing transportation sector creates heavily environmental impacts and is a
      prime cause for the current climate change. The need to reduce emissions from
      this sector has stimulated efforts to speed up the application of electric
      vehicles (EVs). A subset of EVs, called plug-in hybrid electric vehicles (PHEVs),
      backup batteries with combustion engine, which makes PHEVs have a comparable
      driving range to conventional vehicles. However, this hybridization comes at a
      cost of higher emissions than all-electric vehicles. This paper studies the
      routing problem for PHEVs to minimize emissions. The existing shortest-path based
      algorithms cannot be applied to solving this problem, because of the several new
      challenges: (1) an optimal route may contain circles caused by detour for
      recharging; (2) emissions of PHEVs not only depend on the driving distance, but
      also depend on the terrain and the state of charge (SOC) of batteries; (3)
      batteries can harvest energy by regenerative braking, which makes some road
      segments have negative energy consumption. To address these challenges, this
      paper proposes a green navigation algorithm (GNA) which finds the optimal
      strategies: where to go and where to recharge. GNA discretizes the SOC, then
      makes the PHEV routing problem to satisfy the principle of optimality. Finally,
      GNA adopts dynamic programming to solve the problem. We evaluate GNA using
      synthetic maps generated by the delaunay triangulation. The results show that GNA
      can save more than 10 % energy and reduce 10 % emissions when compared to the
      shortest path algorithm. We also observe that PHEVs with the battery capacity of
      10-15 KWh detour most and nearly no detour when larger than 30 KWh. This
      observation gives some insights when developing PHEVs. 

PMID- 27026934
TI  - Comparisons of interdisciplinary ballast water treatment systems and operational
      experiences from ships.
AB  - There are high functioning and low functioning ballast water treatment systems on
      board ships. In this study, five systems were analysed so as to methodically
      examine the operational difficulties for ship crew members while giving important
      consideration to sustainable environment practices. Multi-criteria analysis, a
      questionnaire, survey and interviews were used as the research method so as to
      ascertain and corroborate existing problems on board ships, and the reliability
      of the systems was calculated. The co-insistency, maintenance and the efficiency
      of the systems, were shown as being the major problem as there are no systems for
      tracking ship ballast operations from land. The treatment system that used
      oxidants was, through multi criteria analysis, evaluated as being the best and
      was ranked first. However, the survey results showed that the ship's crew had
      serious problems with this system which difficult to solve during the ship's
      operations with cargo. The deoxygenation system was the most appropriate
      according to ballast water treatment criteria in the port or at sea. The
      treatment system which used electrolysis with oxidant was better in terms of
      efficacy and the treatment system electrolysis with ultra violet light was better
      in terms of the criterion environment pollution footprint. During further
      research, it was shown that 7 % of the surveyed crew members had major problems
      with operating ballast water treatment systems, including the system which was
      ranked first through multi criteria analysis. They by-passed these systems while
      continuing to ballast or de-ballast. It was calculated that of the total time
      needed for the ballast water treatment system operation, 9 % of this time was
      used for repairs or maintenance of the systems. Some examples are changing a used
      UV bulb, cleaning the filter or controlling the amount of oxidant which would be
      discharged into the sea. A conclusion was made and solution was suggested. The
      study results emphasised taking action in the interest of protecting the natural
      world, with particular attention being given to environmental protection to
      support human life. 

PMID- 27026936
TI  - A characterization of L 3(4) by its character degree graph and order.
AB  - Let G be a finite group. The character degree graph [Formula: see text] of G is
      the graph whose vertices are the prime divisors of character degrees of G and two
      vertices p and q are joined by an edge if pq divides the character degree of G.
      Let [Formula: see text] be the projective special linear group of degree n over a
      finite field of order q. Khosravi et. al. have shown that the simple groups
      [Formula: see text], and [Formula: see text] where [Formula: see text] are
      characterizable by the degree graphs and their orders. In this paper, we give a
      characterization of [Formula: see text] by using the character degree graph and
      its order. 

PMID- 27026935
TI  - Improving the thermostability and stress tolerance of an archaeon
      hyperthermophilic superoxide dismutase by fusion with a unique N-terminal domain.
AB  - The superoxide dismutase from the archaeon Sulfolobus solfataricus (SOD Ss ) is a
      well-studied hyperthermophilic SOD with crystal structure and possible
      thermostability factors characterized. Previously, we discovered an N-terminal
      domain (NTD) in a thermophilic SOD from Geobacillus thermodenitrificans NG80-2
      which confers heat resistance on homologous mesophilic SODs. The present study
      therefore aimed to further improve the thermostability and stress tolerance of
      SOD Ss via fusion with this NTD. The recombinant protein, rSOD Ss , exhibited
      improved thermophilicity, higher working temperature, improved thermostability,
      broader pH stability, and enhanced tolerance to inhibitors and organic media than
      SOD Ss without any alterations in its oligomerization state. These results
      suggest that the NTD is an excellent candidate for improving stability of both
      mesophilic and thermophilic SOD from either bacteria or archaea via simple
      genetic manipulation. Therefore, this study provides a general, feasible and
      highly useful strategy for generating extremely thermostable SODs for industrial
      applications. 

PMID- 27026937
TI  - The new workplace II: protocol for a prospective full-panel registry study of
      work factors, sickness absence, and exit from working life among Norwegian
      employees.
AB  - BACKGROUND: Previous studies on the effects of work factors on absence and
      disability retirement have only addressed a limited set of factors and little is
      known about the mechanisms that govern relationships between work exposures and
      sickness absence/disability retirement. The main aims of the present project are
      (1) to examine the impact of a comprehensive set of psychological, social,
      organizational, and mechanical work factors work factors on sickness absence and
      disability retirement, and (2) to identify moderating and mediating variables
      that determine how and when exposures at the workplace are related to sickness
      absence and disability retirement. METHODS: The study design is prospective and
      based on longitudinal survey data linked to registry data on sickness absence and
      disability. Altogether 14,501 respondents have given their permission to the
      linking of their survey questionnaire data to registry data. The project has been
      approved by the Regional Committees for Medical and Health Research Ethics and
      has permission from The Norwegian Data Protection Authority. The questionnaire
      instruments contain psychometrically validated items and inventories on
      demographic background factors, work exposures, individual dispositions and
      attitudes, somatic health, mental distress, well-being, lifestyle factors, and
      work ability. DISCUSSION: The findings will have relevance for, and benefit
      working life and the larger society in a number of ways. Firstly, it will lead to
      a more knowledge about which work factors that contribute to health, sickness
      absence, and participation in/exit from the labour force. Secondly, a better
      understanding of which mediators and moderators that modify and govern these
      relationships. Both are central to the development of laws and regulations and to
      any political decision on measures to tackle sickness absence and early
      retirement.

PMID- 27026938
TI  - Congenital intestinal malrotation in adolescent and adult patients: a 12-year
      clinical and radiological survey.
AB  - Congenital intestinal malrotation is mainly detected in childhood and caused by
      incomplete rotation and fixation of the intestines providing the prerequisites
      for life-threatening volvulus of the midgut. The objective of this study was to
      evaluate a large cohort of adult patients with intestinal malrotation. Thirty
      nine patients, 15-67 years, were diagnosed and admitted to a university setting
      with congenital intestinal malrotation 2002-2013. The patients were divided into
      three age groups for stratified evaluation. Medical charts were scrutinized, and
      clinical outcome of surgery was reviewed. Twelve patients presented as emergency
      cases, whereas 27 were admitted as elective cases. Diagnosis was established in
      33 patients who underwent radiological investigation and in the remaining 6
      during surgery. A Ladd's operation was performed in 31 symptomatic patients; a
      conservative strategy was chosen in eight cases. Volvulus was more common in the
      younger age group. Twenty-six surgically treated patients were available for
      telephone interview, 1-12 years after surgery. All patients, except one, regarded
      their general condition improved to a high degree (n = 18) or with some
      reservation (n = 7). Twelve patients suffered remaining abdominal pain of a
      chronic and diffuse character. Due to recurrence of malrotation six patients were
      reoperated. Symptomatic malrotation occurs in both children and the adult
      population. Improved awareness and an accurately performed CT scan can reveal the
      malformation and enable surgical treatment. A Ladd's procedure relieved most
      patients from their severe complaints even when a history of several years of
      suffering existed. 

PMID- 27026939
TI  - On the linear programming bound for linear Lee codes.
AB  - Based on an invariance-type property of the Lee-compositions of a linear Lee
      code, additional equality constraints can be introduced to the linear programming
      problem of linear Lee codes. In this paper, we formulate this property in terms
      of an action of the multiplicative group of the field [Formula: see text] on the
      set of Lee-compositions. We show some useful properties of certain sums of Lee
      numbers, which are the eigenvalues of the Lee association scheme, appearing in
      the linear programming problem of linear Lee codes. Using the additional equality
      constraints, we formulate the linear programming problem of linear Lee codes in a
      very compact form, leading to a fast execution, which allows to efficiently
      compute the bounds for large parameter values of the linear codes. 

PMID- 27026940
TI  - Brain stem herniation secondary to cerebrospinal fluid drainage in ruptured
      aneurysm surgery: a case report.
AB  - BACKGROUND: A lumbar drainage catheter is frequently placed intra-operatively to
      decrease fluid pressure on the brain in aneurysmal subarachnoid cases. In rare
      cases, this catheter placement can lead to intracranial hypotension, resulting in
      brain stem herniation termed "brain sag" and it can lead to neurological injury
      and may prove to be fatal. We present our patient with brain sag secondary to
      intraoperative lumbar drainage. CASE DESCRIPTION: A 56-year-old woman was
      admitted with a sudden onset of severe headache. A computed tomography (CT) scan
      revealed diffuse subarachnoid hemorrhage with ruptured anterior communicating
      artery aneurysm. After general anesthesia, a lumbar drainage catheter was placed
      intra-operatively to reduce pressure on the brain and 50 cc of CSF was removed
      during a 5-h period. Three to five days after operation, her neurologic symptoms
      became worse with an altered mental state and pupillary asymmetry. CT and
      magnetic resonance imaging (MRI) showed slit lateral ventricles, effacement of
      the cisterns and an elongated brain stem. After placing the patient in the
      Trendelenburg position, the patient rapidly recovered to her baseline neurologic
      state. DISCUSSION: Typical complications of subarachnoid hemorrhage such as
      vasospasm or hydrocephalus also manifest as neurological deterioration, but their
      treatments differ greatly from those for brain sag. Thusly, it is important to
      distinguish between causes. Treatments such as lumbar or extra-ventricular
      drainage, induced hypertension or administration of mannitol must be stopped once
      brain sag is suspected. Also, care should be taken for typical imaging features
      of brain sag on CT or MRI scan. For brain sag, placing the patient in the
      Trendelenburg position can improve neurological status in a rapid fashion.
      CONCLUSIONS: Brain sag is a rare but serious condition and can be fatal if not
      rapidly diagnosed and treated. We therefore recommend including brain sag in the
      differential diagnosis, along with vasospasm, hydrocephalus or cerebral edema as
      part of possible complications following subarachnoid hemorrhage treatment. We
      hope our clinical and imaging data from this case study contribute to the correct
      diagnosis of brain sag, as its early detection is important.

PMID- 27026941
TI  - A feature selection approach based on term distributions.
AB  - Feature selection has a direct impact on text categorization. Most existing
      algorithms are based on document level, and they haven't considered the influence
      of term frequency on text categorization. Based on these, we put forward a
      feature selection approach, FSATD, based on term distributions in the paper. In
      our proposed algorithm, three critical factors which are term frequency, the
      inter-class distribution and the intra-class distribution of the terms are all
      considered synthetically. Finally, experiments are made with the help of kNN
      classifier. And the corresponding results on 20NewsGroup and SougouCS corpus show
      that FSATD algorithm achieves better performance than DF and t-Test algorithms. 

PMID- 27026943
TI  - A prospective pilot study of analysis of surgical margins of breast cancers using
      high-resolution sonography.
AB  - To investigate the role of high-resolution specimen sonography (SS) to determine
      the precise location of the targeted lesion in relation to the six surgical
      margins; the specimen digital radiography isocenter and the correlation with the
      rate of re-excision and residual tumour. Freshly excised surgical specimens were
      scanned by a breast radiologist using a high-frequency linear transducer in a
      cohort of 25 consecutive women undergoing breast conservation. Sonographic
      measurements of radial distances from all six margins (superior, inferior,
      lateral, medial, anterior and posterior) were obtained. Sonographic positive
      margin status was defined as targeted mass identified <5 mm from the tissue edge.
      The paired t test was used for statistical comparisons between sonographic and
      pathological measurements. The median cancer size was 15 mm (range 3.80-42 mm; 95
      % CI 9.8-18) on sonography and 16 mm (range 2-60 mm; 95 % CI 15-20) on surgical
      pathology. SS showed 100 % sensitivity and 59 % specificity in the evaluation of
      surgical pathology margins. 20 % (5 of 25) patients had positive margins where 60
      % were in situ carcinoma. The likelihood of carcinoma at the initial surgical
      margins was significantly higher in dense breasts (3/6 = 50 % vs 1/17 = 5.8 %; p
      = 0.04). The deviation of the isocenter of the specimens was found not
      significant. SS is a valuable tool for identify the cancer within the specimen,
      and better asses the margins. It is of significant importance in patients with
      dense breasts where specimen radiography is of limited value. 

PMID- 27026942
TI  - Formations of calcium carbonate minerals by bacteria and its multiple
      applications.
AB  - Biomineralization is a naturally occurring process in living organisms. In this
      review, we discuss microbially induced calcium carbonate precipitation (MICP) in
      detail. In the MICP process, urease plays a major role in urea hydrolysis by a
      wide variety of microorganisms capable of producing high levels of urease. We
      also elaborate on the different polymorphs and the role of calcium in the
      formation of calcite crystal structures using various calcium sources.
      Additionally, the environmental factors affecting the production of urease and
      carbonate precipitation are discussed. This MICP is a promising, eco-friendly
      alternative approach to conventional and current remediation technologies to
      solve environmental problems in multidisciplinary fields. Multiple applications
      of MICP such as removal of heavy metals and radionuclides, improve the quality of
      construction materials and sequestration of atmospheric CO2 are discussed. In
      addition, we discuss other applications such as removal of calcium ions, PCBs and
      use of filler in rubber and plastics and fluorescent particles in stationary ink
      and stationary markers. MICP technology has become an efficient aspect of
      multidisciplinary fields. This report not only highlights the major strengths of
      MICP, but also discusses the limitations to application of this technology on a
      commercial scale. 

PMID- 27026944
TI  - Trinitrotoluene and mandarin peels selectively affect lignin-modifying enzyme
      production in white-rot basidiomycetes.
AB  - Five white-rot basidiomycetes (WRB) species have been evaluated for their
      potential to tolerate and to degrade 0.2 mM 2, 4, 6-trinitrotoluene (TNT) as well
      as to produce laccase and manganese peroxidase (MnP) in presence of this
      xenobiotic. The tested fungal strains produced laccase in both glycerol and
      mandarin peels-containing media, whereas in the glycerol-containing medium only
      Cerrena unicolor strains and Trametes versicolor BCC 775 secreted MnP.
      Replacement of glycerol by milled mandarin peels 3- to 45-fold increased laccase
      activity, promoted C. unicolor strains and T. versicolor MnP secretion and
      induced this enzyme production by Fomes fomentarius BCC 38 and Funalia trogii BCC
      146. Differential response of the WRB strains to the TNT addition was observed.
      In particular, laccase activity of C. unicolor increased 2- to 3-fold in both
      media whereas no stimulation of the laccase production was revealed in
      cultivation of F. fomentarius. TNT practically did not affect the MnP activity.
      Two strains of C. unicolor followed by T. versicolor producing laccase and MnP
      almost completely removed 0.2 mM TNT from the synthetic medium. Increase of TNT
      concentration from 0 to 0.4 mM in the mandarin peels-based medium and from 0 to
      0.3 mM in the glycerol-containing medium stimulated C. unicolor BCC 300 laccase
      production from 92.4 to 240.7 U/ml and from 17.1 to 48.6 U/ml, respectively. This
      strain has been resistant to the TNT high concentration and has ability to remove
      85 % of initial 0.3 mM TNT content during 6 days of the submerged cultivation. 

PMID- 27026945
TI  - Development of a monitoring scheme for preventive maintenance of the cement
      machinery.
AB  - It was underscored that the optimization of policies of preventive maintenance
      has become a subject of much research. This article proposes a new optimal policy
      of preventive maintenance for the roller shaft system. It is divided into two
      main sections. The first proposes a new design of the shaft where the effect of
      preventive maintenance is integrated, and the second is developing a new control
      technique adapted to the new design. In this regard, we are interested in the
      shaft of rollers of the rotary kilns of cement. We have noted the stresses
      imposed to the axis of the roller. These constraints that have stemmed from the
      contact between tire and its support rollers. Currently the ultrasonic inspection
      method of the solid shaft in this situation poses disadvantages, for example, the
      obligation to stop the rotary Kiln and the difficulty of detecting and sizing
      defects (fatigue cracks). We propose in this study another approach, we recommend
      opting for a hollow shaft instead of a solid shaft with a minimum diameter that
      allows the control system to enter hollow shaft to show for inspection purposes.
      This will allow preventive control, in operation by the non-destructive technique
      of ultrasound. The analysis shows the different results of comparison between the
      axis of full and hollow cylinders, having the same dimensions and the same
      material and ultimately the most interesting is the same operation. 

PMID- 27026946
TI  - Rural settlements dynamics and the prospects of densification strategy in rural
      Bangladesh.
AB  - Given the year on year decrease of rural farmland and various forms of land
      degradation through the intrusion of non-farm land uses, the government of
      Bangladesh has drafted the agrarian reform strategies, primarily to protect the
      agricultural land from encroachment, conversion, and indiscriminate use. The
      draft Agricultural Land Protection and Land Use Bill since its inception in 2011
      is facing serious uncertainties of implementation due to its borrowed nature from
      the developed contexts and inadequacy to recognize the local complexities. With a
      particular focus on the densification component of the draft bill, a semester
      long design studio was conducted in consultation with the existing villagers to
      explore the practicability of the draft bill in the villages of Tetultala and
      Chhoygharia in the south-western coastal Bangladesh. The findings from the two
      villages hint that in Bangladesh, the unique and evolving nature of rural
      settlements dynamics that are disintegrating the rural society from farming
      practices and the farmland, thereby, unsettling the traditional village
      morphology. The settlements dynamics vary from those of the western context;
      hence, there is an emerging need to build locally situated knowledge towards a
      feasible rural land reform. 

PMID- 27026947
TI  - Residual phosphorus and zinc influence wheat productivity under rice-wheat
      cropping system.
AB  - Continuous cropping of rice (Oryza sativa L.) and wheat (Triticum aestivum L.)
      deplete soil fertility and crop productivity. One strategy to increase crop
      productivity under rice-wheat system is balanced application of crop nutrients.
      Field experiment was conducted to assess the impact of phosphorus (0, 40, 80, 120
      kg P ha(-1)) and zinc (0, 5, 10, 15 kg Zn ha(-1)) on the productivity of rice
      genotypes (fine and coarse) and their residual effects on the grain yield (GY)
      and its components (YC) of the succeeding wheat crop under rice-wheat cropping
      system (RWCS) in North Western Pakistan during 2011-12 and 2012-13. After rice
      harvest in both years, wheat variety "Siren-2010" was grown on the same layout
      but no additional P, K and Zn was applied to wheat crop in each year. The GY and
      YC of wheat significantly increased in the treatments receiving the higher P
      levels (120 > 80 > 40 > 0 kg P ha(-1)) and Zn (15 > 10 > 5 > 0 kg Zn ha(-1)) in
      the previous rice crop. The residual soil P and Zn contents after rice harvest,
      GY and YC of wheat increased significantly under low yielding fine genotype (B
      385) as compared to the high yielding coarse genotypes (F-Malakand and Pukhraj).
      The residual soil P and Zn, GY and of wheat increased significantly in the second
      year as compared with the first year of experiment. These results confirmed
      strong carry over effects of both P and Zn applied to the previous rice crop on
      the subsequent wheat crop under RWCS. 

PMID- 27026948
TI  - Saturation of electrical resistivity of solid iron at Earth's core conditions.
AB  - We report on the temperature dependence of the electrical resistivity of solid
      iron at high pressure, up to and including conditions likely to be found at the
      centre of the Earth. We have extended some of the calculations of the
      resistivities of pure solid iron we recently performed at Earth's core conditions
      (Pozzo et al. in Earth Planet Sci Lett 393:159-164, 2014) to lower temperature.
      We show that at low temperature the resistivity increases linearly with
      temperature, and saturates at high temperature. This saturation effect is well
      known as the Mott-Ioffe-Regel limit in metals, but has been largely ignored to
      estimate the resistivity of iron at Earth's core conditions. Recent experiments
      (Gomi et al. in Phys Earth Planet Int 224:88-103, 2013) coupled new high pressure
      data and saturation to predict the resitivity of iron and iron alloys at Earth's
      core conditions, and reported values up to three times lower than previous
      estimates, confirming recent first principles calculations (de Koker et al. in
      Proc Natl Acad Sci 109:4070-4073, 2012; Pozzo et al. in Nature 485:355-358, 2012,
      Phys Rev B 87:014110-10, 2013, Earth Planet Sci Lett 393:159-164, 2014; Davies et
      al. in Nat Geosci 8:678-685, 2015). The present results support the saturation
      effect idea. 

PMID- 27026949
TI  - Comparison of EBT and EBT3 RadioChromic Film Usage in Parotid Cancer
      Radiotherapy.
AB  - BACKGROUND: EBT and EBT3 radioChromic films have been used in radiotherapy
      dosimetry for years. OBJECTIVE: The aim of the current study is to compare EBT
      and EBT3 radioChromic films in dosimetry of radiotherapy fields for treatment of
      parotid cancer. METHODS: Calibrations of EBT and EBT3 films were performed with
      identical setups using a 6 MV photon beam of a Siemens Primus linac. Skin dose
      was measured at different points in the right anterior oblique (RAO) and right
      posterior oblique (RPO) fields by EBT and EBT3 films on a RANDO phantom. RESULTS:
      While dosimetry was performed with the same conditions for the two film types for
      calibration and in phantom in parotid cancer radiotherapy, the measured net
      optical density (NOD) in EBT film was found to be higher than that from EBT3
      film. The minimum difference between these two films under calibration conditions
      was about 2.9% (for 0.2 Gy) with a maximum difference of 35.5% (for 0.5 Gy). In
      the therapeutic fields of parotid cancer radiotherapy at different points, the
      measured dose from EBT film was higher than the EBT3 film. In these fields the
      minimum and maximum measured dose differences were 16.0% and 25.5%, respectively.
      CONCLUSION: EBT film demonstrates higher NOD than EBT3 film. This effect may be
      related to the higher sensitivity of EBT film over EBT3 film. However, the
      obtained dose differences between these two films in low dose range can be due to
      the differences in fitting functions applied following the calibration process.

PMID- 27026950
TI  - Diagnosis and Treatment of Small Bowel Cancers Using Radioactive Gold
      Nanoparticles and Wireless Fluorescence Capsule Endoscopy.
AB  - BACKGROUND: Therapeutic and diagnosis properties of radioactive gold nanoparticle
      (198-AuNPs) cause them to be suitable for detection and treatment of tumors.
      OBJECTIVE: Electrical and optical properties of PEG-198AuNPs were examined in
      this paper. Polyethylene Glycol (PEG)-198 AuNPs can be used for treatment and
      diagnosis of small intestine tumors. METHODS: Wireless fluorescence capsule
      endoscopy will be able to detect emission lights of triggered Au by external
      light. First, the output electrical field was calculated by DDSCAT software.
      Secondly, tumor and distribution of PEG-198 gold nanoparticles were modeled using
      Monte Carlo simulation and finally dose delivered throughout a solid tumor when
      the PEG-198 gold nanoparticles linked to each cell was calculated. RESULTS:
      Polyethylene Glycol functionalized gold nanoparticles (AuNPs) possess optimized
      sizes (30 nm core diameter and 70 nm hydrodynamic diameters) to target individual
      tumor cells. Surface distribution to receive doses of up to 50Gy was simulated. 
      Activities and absorbed doses by the tumors with 0.25cm and 0.5cm radius were
      187.9mCi and 300mCi and 72 and 118 Gy,respectively. CONCLUSION: Therapeutic and
      diagnosis properties of 198-AuNPs show that it can be used for treatment and
      detection of small bowel tumors in early stage of growing.

PMID- 27026951
TI  - A Novel Biological Dosimetry Method for Monitoring Occupational Radiation
      Exposure in Diagnostic and Therapeutic Wards: From Radiation Dosimetry to
      Biological Effects.
AB  - BACKGROUND AND OBJECTIVE: Professional radiation workers are occupationally
      exposed to long-term low levels of ionizing radiation. Occupational health
      hazards from radiation exposure, in a large occupational segment of the
      population, are of special concern. Biological dosimetry can be performed in
      addition to physical dosimetry with the aim of individual dose assessment and
      biological effects. METHODS: In this biodosimetry study, some hematological
      parameters have been examined in 40 exposed and 40 control subjects who were
      matched by gender, age and occupational records (+/-3 years) in Kermanshah
      hospitals in Iran (2013-2014). The occupational radiation dose was measured by
      personal dosimetry device (film badges). The data was analyzed using SPSS V.20
      and statistical tests such as two-sided Student's t-test. RESULTS: Exposed
      subjects had a median exposure of 0.68+/-1.58 mSv/year by film badge dosimetry.
      Radiation workers with at least a 10-year record showed lower values of Mean
      Hemoglobin (Hb) and Mean Corpuscular Volume (MCV) compared to the control group
      (p<0.05). The mean value of Red Blood Cells (RBCs) in personnel working in
      Radiology departments seemed to show decrease in comparison with other radiation
      workers. CONCLUSION: Although the radiation absorbed doses were below the
      permissible limits based on the ICRP, this study showed the role of low-level
      chronic exposure in decreasing Hb and MCV in the blood of radiation workers with
      at least 10 years records. Therefore, the findings from the present study suggest
      that monitoring of hematological parameters of radiation workers can be useful as
      biological dosimeter, and also the exposed medical personnel should carefully
      follow the radiation protection instructions and radiation exposure should be
      minimized as possible.

PMID- 27026952
TI  - Short-Term Exposure to Electromagnetic Fields Generated by Mobile Phone Jammers
      Decreases the Fasting Blood Sugar in Adult Male Rats.
AB  - BACKGROUND: Substantial evidence indicates that exposure to electromagnetic
      fields (EMF) above certain levels can affect human health through triggering some
      biological responses. According to WHO, short-term exposure to EMF at the levels
      present in the home/environment do not cause any apparent detrimental effects in
      healthy individuals. However, now, there is a debate on whether long-term
      exposure to low level EMF can evoke detrimental biological responses. Although
      based on the Communications Act of 1934, selling, advertising, using, or
      importing mobile jammers which block cell phone calls and text messages are
      illegal acts, in some countries these devices are being used for security purpose
      and for prevention of cheating during examinations. METHODS: In this study 30
      male Wistar rats were randomly divided into 3 groups of 10 each. The control
      group received no radiation. The sham exposure group was exposed to a switched
      off jammer device. After fasting for 12 hours, the exposure group was exposed to
      EMFs at a distance of 50 cm from the jammer. Blood samples were collected from
      the tail vein after 24, 48 and72 hours and fasting blood sugar was measured by
      using a common blood glucose monitor (BIONIME GM110, Taiwan). The significance
      level was considered 5% and SPSS Ver. 21 was used for statistical analysis. The
      data were analyzed by ANOVA followed by Tukey's test. RESULTS: A statistically
      significant difference was observed between blood sugar level in the control and
      exposure groups after 24, 48 and 72 hours of continuous irradiation (p values
      were <0.001, <0.001 and 0.002, respectively). No significant difference was found
      between the level of fasting blood sugar in control and sham groups. CONCLUSION:
      Short-term exposure to electromagnetic field generated by mobile phone jammer can
      reduce blood sugar level in adult male rats. These findings, in contrast with our
      previous results, lead us to this conclusion that the use of these signal
      blocking devices in very specific circumstances may have some therapeutic
      effects. However, further studies have to be performed to find out the exact
      mechanism by which Jammer EMFs reduce fasting blood sugar.

PMID- 27026953
TI  - A Lumped Parameter Method to Calculate the Effect of Internal Carotid Artery
      Occlusion on Anterior Cerebral Artery Pressure Waveform.
AB  - BACKGROUND AND OBJECTIVE: Numerical modeling of biological structures would be
      very helpful tool to analyze hundreds of human body phenomena and also diseases
      diagnosis. One physiologic phenomenon is blood circulatory system and heart
      hemodynamic performance that can be simulated by utilizing lumped method. In this
      study, we can predict hemodynamic behavior of one artery of circulatory system
      (anterior cerebral artery) when disease such as internal carotid artery occlusion
      is occurred. METHOD: Pressure-flow simulation is one the leading common
      approaches for modeling of circulatory system behavior and forecasts of
      hemodynamic in numerous physiological conditions. In this paper, by using lumped
      model (electrical analogy), CV system is simulated in MATLAB software (SIMULINK
      environment). RESULTS: The performance of healthy blood circulation and heart is
      modeled and the obtained results used for further analyses. The stenosis of
      internal carotid artery at different rates was, then, induced in the circuit and
      the effects are studied. In stenosis cases, the effects of internal carotid
      artery occlusion on  left anterior cerebral artery pressure waveform are
      investigated. CONCLUSION: The findings of this study may have implications not
      only for understanding the behavior of human biological system at healthy
      condition but also for diagnosis of diseases in circulatory and cardiovascular
      system of human body.

PMID- 27026954
TI  - Increased Release of Mercury from Dental Amalgam Fillings due to Maternal
      Exposure to Electromagnetic Fields as a Possible Mechanism for the High Rates of
      Autism in the Offspring: Introducing a Hypothesis.
AB  - According to the World Health Organization (WHO), factors such as growing
      electricity demand, ever-advancing technologies and changes in social behaviour
      have led to steadily increasing exposure to man-made electromagnetic fields. 
      Dental amalgam fillings are among the major sources of exposure to elemental
      mercury vapour in the general population. Although it was previously believed
      that low levels are mercury (i.g. release of mercury from dental amalgam) is not
      hazardous, now numerous data indicate that even very low doses of mercury cause
      toxicity. There are some evidence indicating that perinatal exposure to mercury
      is significantly associated with an increased risk of developmental disorders
      such as autism spectrum disorders (ASD) and attention-deficit hyperactivity
      disorder (ADHD). Furthermore, mercury can decrease the levels of
      neurotransmitters dopamine, serotonin, noreprenephrine, and acetylcholine in the
      brain and cause neurological problems. On the other hand, a strong positive
      correlation between maternal and cord blood mercury levels is found in some
      studies. We have previously shown that exposure to MRI or microwave radiation
      emitted by common mobile phones can lead to increased release of mercury from
      dental amalgam fillings. Moreover, when we investigated the effects of MRI
      machines with stronger magnetic fields, our previous findings were confirmed. As
      a strong association between exposure to electromagnetic fields and mercury level
      has been found in our previous studies, our findings can lead us to this
      conclusion that maternal exposure to electromagnetic fields in mothers with
      dental amalgam fillings may cause elevated levels of mercury and trigger the
      increase in autism rates. Further studies are needed to have a better
      understanding of the possible role of the increased mercury level after exposure
      to electromagnetic fields and the rate of autism spectrum disorders in the
      offspring. 

PMID- 27026955
TI  - USE OF CORTICAL STRUCTURAL HOMOLOGOUS BONE GRAFT IN FEMORAL RECONSTRUCTIVE
      SURGERY.
AB  - To perform a clinical and radiographic assessment of patients undergoing surgical
      treatment using a cortical structural homologous bone graft for femoral
      reconstruction following mechanical failure of total hip arthroplasty and
      periprosthetic fractures. METHODS: A retrospective study was conducted on 27
      patients who underwent surgical treatment for femoral reconstruction following
      mechanical failure of total hip arthroplasty (12 cases) and periprosthetic
      fractures (15 cases), using a cortical structural homologous bone graft and
      cemented implants, between June 1999 and February 2008. Of these, 21 fulfilled
      all the criteria required for this study. The patients underwent pre and
      postoperative clinical assessments using the Harris Hip Score. Preoperative,
      immediate postoperative and late postoperative radiographs were also evaluated,
      with comparisons of fracture consolidation, radiographic signs of graft
      consolidation, changes to the bone stock and femoral bone quality, and femoral
      alignment. RESULTS: Nine patients (42.9%) underwent femoral reconstruction
      following mechanical failure of total hip arthroplasty and 12 cases (57.1%)
      underwent femoral reconstruction following periprosthetic fracture. Regarding the
      postoperative clinical classification, the results were considered satisfactory
      in 85.7% of the cases and unsatisfactory in 14.3%. Radiographic signs of graft
      consolidation were seen in all cases. There was an increase in bone stock in
      90.5% of the hip reconstructions, as measured by the cortical index. Furthermore,
      the changes to femoral bone quality were considered good in 66.7% of the cases.
      CONCLUSION: The use of cortical structural homologous bone grafts for both
      femoral reconstructive surgery on total hip arthroplasty and periprosthetic
      fractures is a good treatment option for selected cases, enabling satisfactory
      clinical and radiographic results.

PMID- 27026956
TI  - EXTENSIVE OSTEOLYSIS AFTER THE USE OF A BIOABSORBABLE SUTURE ANCHOR: CASE REPORT
      AND LITERATURE REVIEW.
AB  - Bioabsorbable implants are very frequently used to treat rotator cuff and
      shoulder labrum injuries. Many researchers have observed small areas of
      osteolysis after treating pathological conditions of the shoulder using
      bioabsorbable anchors. Biological and mechanical theories have been put forward
      to account for the osteolysis caused by these materials. The case of a patient
      who was simultaneously treated for a rotator cuff lesion using the double-row
      technique and a Bankart lesion using bioabsorbable PLLA anchors and Fiber
      Wire(r), and developed extensive osteolysis of the anatomical neck of the
      humerus, is described. Given that an anchor was used in the glenoid, and this did
      not present osteolysis, the hypothesis that mechanical factors are important in
      the etiology of this complication is raised. 

PMID- 27026957
TI  - UPDATE ON INFECTIONS IN ARTICULAR PROSTHESIS.
AB  - The implantation of joint prostheses, especially for the hip and knee, is
      becoming increasingly common. This provides a significant reduction in discomfort
      and an immeasurable improvement in patient mobility. Reviews of the worldwide
      literature indicate that 1 to 5% of these prostheses become infected, although it
      is important to remember that as the number of operations performed to implant
      these prosthesis increases, so will the number of cases of this type of
      infection. Gram-positive bacteria predominate in contaminations of joint
      prostheses, in particular Staphylococcus aureus and Staphylococcus epidermidis.
      Infections caused by gram-negative bacilli and fungi such as Candida sp have been
      reported with increased frequency throughout the world. Infections of joint
      prostheses present characteristic signs that can be divided into acute
      manifestations (severe pain, high fever, toxemia, heat, redness and wound
      secretions) and chronic manifestations (progressive pain, cutaneous fistula
      formation and pus drainage, without fever). The definitive diagnosis of the
      infection should be made through cultures to isolate the microorganism, using
      material collected from joint fluid puncture, surgical wound secretions, and
      surgical debridement. It is essential to cover for methicillin-resistant
      Staphylococcus aureus, given the epidemiological importance of this agent in
      these infections. The total duration of antibiotic therapy ranges from six weeks
      to six months, and this treatment should be adjusted as needed, based on the
      results from culturing. 

PMID- 27026958
TI  - BONE BANKS.
AB  - Bone banks are necessary for providing biological material for a series of
      orthopedic procedures. The growing need for musculoskeletal tissues for
      transplantation has been due to the development of new surgical techniques, and
      this has led to a situation in which a variety of hospital services have been
      willing to have their own source of tissue for transplantation. To increase the
      safety of transplanted tissues, standards for bone bank operation have been
      imposed by the government, which has limited the number of authorized
      institutions. The good performance in a bone bank depends on strict control over
      all stages, including: formation of well-trained harvesting teams; donor
      selection; conducting various tests on the tissues obtained; and strict control
      over the processing techniques used. Combination of these factors enables greater
      scope of use and numbers of recipient patients, while the incidence of tissue
      contamination becomes statistically insignificant, and there is traceability
      between donors and recipients. This paper describes technical considerations
      relating to how a bone bank functions, the use of grafts and orthopedic
      applications, the ethical issues and the main obstacles encountered. 

PMID- 27026959
TI  - EVALUATION OF THE RESULTS OF SURGICAL TREATMENT OF POSTTRAUMATIC STIFFNESS OF THE
      ELBOW IN SKELETALLY MATURE PATIENTS.
AB  - OBJECTIVE: To evaluate the results from surgical treatment of posttraumatic
      stiffness of the elbow in skeletally mature patients. METHODS: Between October
      2000 and October 2007, 45 elbows of 45 patients underwent surgical treatment
      performed by the Shoulder and Elbow Surgery Group, Department of Orthopedics and
      Traumatology, School of Medical Sciences, Santa Casa de Sao Paulo. Ten patients
      were treated arthroscopically and the remainder by open surgery. The minimum
      follow-up was six months, with a mean of 22 months. Their ages ranged from 17 to
      72 years, with a mean of 36 years and three months. Males predominated,
      accounting for 60% of the cases. The dominant limb was involved in 56.5% of the
      cases. The clinical evaluation of the results was done by using the criteria of
      the American Medical Association (AMA), as modified by Bruce; the Mayo Elbow
      Performance Score (MEPS); and measurements on the gain of flexion-extension arc
      and the final range of motion. RESULTS: According to the AMA criteria, as
      modified by Bruce, 42.2% of our results were satisfactory, whereas 77.8% were
      satisfactory according to MEPS. The mean postoperative flexion-extension arc was
      106 degrees , and the main gain in range was 46 degrees . The evaluation of the
      variables showed that patients with an initial flexion arc greater than 90
      degrees  achieved a greater final flexion-extension arc, and those with an
      initial extension less than or equal to 60 degrees  gained greater range of
      motion. CONCLUSION: Surgical treatment of posttraumatic stiffness of the elbow in
      skeletally mature individuals was shown to be satisfactory according to MEPS, but
      unsatisfactory according to AMA. We observed that the patients with preoperative
      flexion greater than 90 degrees  evolved with a greater flexion-extension arc
      after surgical treatment, while those who had contracture with extension less
      than or equal to 60 degrees  gained a greater range of motion.

PMID- 27026960
TI  - ANTERIOR GLENOID RIM EROSION MEASURED BY X-RAY EXAM: A SIMPLE WAY TO PERFORM THE
      BERNAGEAU PROFILE VIEW.
AB  - OBJECTIVE: To analyze whether the Bernageau radiographic view is adequate for
      studying the anterior glenoid rim and to determine the distance between the
      posterior and anterior glenoid rims. METHODS: Fifty patients (31 males) with a
      mean age of 34 years were evaluated by positioning their arm at 160 degrees 
      forward flexion and body at 70 degrees  to the x-ray chassis, while positioning
      the x-ray tube at 30 degrees  craniocaudally, centered on the scapula spine.
      Three of the authors measured the distance between the posterior and anterior
      glenoid rim three times. The variability and reproducibility of this distance
      were studied. Three shoulder surgeons performed a subjective evaluation by
      answering whether it was possible to evaluate the anterior glenoid rim in the
      view studied. RESULTS: The mean distance was 24.48 mm +/- 0.332 mm (left) and
      24.82 mm +/- 0.316 mm (right). The Anderson-Darling test showed that the
      measurements had normal distribution, and Pearson's correlation showed
      significant reproducibility (P < 0.01). The first observer found that 67% of the
      x-ray images were suitable for evaluating the anterior glenoid rim. The second
      found that 81% were suitable and the third, 78%. The kappa coefficient showed
      that the second and third observers had substantial agreement of opinion.
      CONCLUSION: The Bernageau view provided a suitable x-ray image for studying the
      anterior glenoid rim and for assessing erosion after comparison with the
      unaffected side.

PMID- 27026961
TI  - PROXIMAL TIBIAL OSTEOTOMY: STABILIZATION OF THE MEDIAL OPENING WITH A TRICORTICAL
      ILIAC BONE GRAFT.
AB  - OBJECTIVE: Radiographic assessment of lower limb alignment, in the frontal and
      sagittal planes, after high tibial osteotomy. To stabilize the osteotomy, a
      tricortical iliac graft was used, along with a positioning screw. METHODS:
      Prospective study on 46 patients with ages ranging from 17 to 61 years. Among
      them, 42 patients presented genu varum secondary to knee osteoarthritis and four
      from other causes. Teleradiography was performed for surgical planning, using the
      Frank Noyes method, as modified by Fugizawa. A conventional surgical access of 3
      cm was made to harvest a tricortical iliac graft. Osteotomy was performed under
      radioscopic control, by means of an anteromedial incision of 3 cm with release of
      the superficial portion of the medial collateral ligament. The graft was placed
      in the posterior portion of the osteotomy, to maintain an unaltered tibial slope.
      The screw crossed the osteotomy orthogonally to protect the lateral cortex. Pre
      and postoperative radiographic criteria were established to assess the results.
      RESULTS: There was consolidation in 100% of the cases and maintenance of the
      mechanical axis, obtained intraoperatively, in 94% of the cases. The posterior
      slope of the tibial plateau in the sagittal plane ranged from 7 degrees  to 12
      degrees . Joint mobility was restored in all the patients. Eleven patients
      presented temporary pain at the site of graft harvesting, but none had
      paresthesia. The incidence of complications was 8% (infection, loss of correction
      and joint fracture). CONCLUSION: The technique was shown to be reproducible,
      simple, biological, accurate and low-cost, and it may be an alternative to the
      existing techniques.

PMID- 27026962
TI  - SIX MONTH FOLLOW-UP OF PATIENTS SUBMITTED TO TOTAL KNEE ARTHROPLASTY WITH AND
      WITHOUT PLACEMENT OF SUCTION DRAINAGE DEVICES.
AB  - OBJECTIVE: The aim of this study was to prospectively evaluate the evolution and
      postoperative complication patterns relating to the use of suction drains, in
      comparison with not using these devices in total knee arthroplasty (TKA)
      procedures. METHODS: Forty-two patients at a knee surgery referral clinic were
      included. Fifteen patients did not receive suction drainage postoperatively and
      27 received suction drainage. The parameters evaluated were the range of motion,
      hematological indices, knee circumference and complication rate. The observation
      period was for six months after the surgical procedure. RESULTS: There were no
      statistically significant differences between the groups regarding knee
      circumference, hemoglobin, hematocrit, transfusion rate or infection index.
      Regarding range of motion, there was no statistically significant difference
      between the groups with and without drains preoperatively (p = 0.126), during the
      first postoperative day (p = 0.583), on the fifth to seventh postoperative day (p
      = 0.076) or at the six-month follow-up (p = 0.848). There was a statistically
      significant difference between the groups in the evaluation performed between the
      14th and 28th postoperative days (p = 0.025). CONCLUSION: From this study, it was
      concluded that there was no benefit from using closed suction drains in TKA cases
      beyond six months after the operation. However, the range of movement at the end
      of the first month was greater in the patients that received suction drainage.

PMID- 27026963
TI  - OUTCOME OF ROTATOR CUFF REPAIR IN SNYDER TYPE Cl AND C2 LESIONS, CONSIDERING
      SMOKERS AND NONSMOKERS.
AB  - OBJECTIVE: To evaluate the influence of smoking on the results from surgical
      repair of Snyder type C1 and C2 complete lesions of the rotator cuff. METHODS: We
      evaluated 166 patients who had undergone surgical treatment for Snyder type C1
      and C2 complete lesions of the rotator cuff, between June 2002 and December 2006.
      The inclusion criteria were a minimum follow-up period of 24 months and the
      absence of previous surgery on the affected shoulder. Patients with other
      associated injuries were excluded. We evaluated smoking and nonsmoking patients
      in accordance with the criteria of the World Health Organization (WHO). Female
      patients (119) predominated over male patients (47), and the mean age was 57
      years (38 to 78). Out of the 166 patients evaluated, 21 were classified as
      smokers and 145 as nonsmokers. The final results were evaluated using the UCLA
      (University of California at Los Angeles) criteria and statistical analysis was
      performed using the Epi Info((r)) software. RESULTS: According to the UCLA
      criteria, smokers had a final average of 32.6 points, while non-smokers had 33.8.
      Postoperative statistical analysis revealed a difference between the two groups,
      such that non-smoking patients had a better outcome. CONCLUSION: Smoking
      interferes with the final results from repairs of small and medium-sized lesions
      of the rotator cuff.

PMID- 27026964
TI  - FUNCTIONAL AND RADIOGRAPHIC COMPARISON OF ANTERIOR AND POSTERIOR INSTRUMENTATION
      FOR THE CORRECTION OF ADOLESCENT IDIOPATHIC SCOLIOSIS.
AB  - OBJECTIVE: This was a retrospective study to compare the anterior instrumentation
      (AI) and posterior instrumentation (PI) results among patients diagnosed with
      adolescent idiopathic scoliosis (Lenke type I) who were treated surgically.
      METHODS: The results from 24 patients aged 11 to 18 years with Lenke type I
      idiopathic scoliosis who underwent surgery with AI (12 patients) or PI (12
      patients) were compared. All the patients were operated by the same surgeon and
      were followed up for a minimum period of five years. The variables for comparison
      included: coronal and sagittal correction, distance from apical vertebra to
      midline, apical vertebral rotation, number of instrumented vertebrae and
      functional variables (by means of the SRS-22 questionnaire). The data obtained
      were analyzed using the SAS software, version 9. The two groups were compared
      using Student's t-test with a significance level of 5% (0.05). RESULTS: The
      correction of the curve in the frontal plane was higher in the group of patients
      with the anterior approach, in the immediate (p=0.031) and late (p=0.043)
      postoperative periods, as was the apical vertebral rotation during the immediate
      (p=0.002) and late (p=0.019) evaluations. The number of instrumented vertebrae
      was 7.69 +/- 1.38 in the AI group and 11.38 +/- 2.92 in the PI group (p = 0.021).
      Functional assessment (SRS-22) did not show any significant difference (p > 0.05)
      between the groups. CONCLUSION: The patients who underwent scoliosis correction
      with AI presented greater correction in the frontal plane, greater derotation of
      apical vertebrae and a smaller number of fused vertebrae.

PMID- 27026965
TI  - EFFECT OF PILOT HOLE TAPPING ON PULLOUT STRENGTH AND INSERTION TORQUE OF DUAL
      CORE PEDICLE SCREWS.
AB  - OBJECTIVE: To evaluate the influence of pilot hole tapping on pullout resistance
      and insertion torque of pedicle screws with a conical core. METHODS: Mechanical
      tests using a universal testing machine were performed on pedicle screws with a
      conical core that were inserted into pedicles in the fifth lumbar vertebra of
      calves. The insertion torque was measured using a torque meter with a capacity of
      10 Nm, which was considered to be the highest torque value. The pilot holes were
      prepared using a probe of external diameter 3.8 mm and tapping of the same
      dimensions and thread characteristics as the screw. RESULTS: Decreased insertion
      torque and pullout resistance were observed in the group with prior tapping of
      the pilot hole. CONCLUSIONS: Pilot hole tapping reduced the insertion torque and
      pullout resistance of pedicle screws with a conical core that had been inserted
      into the pedicle of the fifth lumbar vertebra of calves.

PMID- 27026966
TI  - PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS
      PULPOSUS.
AB  - OBJECTIVE: To evaluate the effect of anti-inflammatory drugs (dexamethasone,
      indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs
      (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in
      contact with the L5 dorsal root ganglion (DRG). METHODS: Thirty male Wistar rats
      of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was
      induced by means of a fragment of NP removed from the sacrococcygeal region that
      was placed in contact with the L5 dorsal root ganglion. The 30 animals were
      divided into experimental groups according to the drug used. The drugs were
      administered for two weeks after the surgical procedure to induce hyperalgesia.
      Mechanical and thermal hyperalgesia was evaluated using the paw pressure test,
      von Frey electronic test and Hargreaves test, over a seven-week period. RESULTS:
      The greatest reduction of hyperalgesia was observed in the group of animals
      treated with morphine, followed by dexamethasone, indomethacin and atenolol.
      Reductions in hyperalgesia were observed after drug administration ceased, except
      for the group of animals treated with morphine, in which there was an increase in
      hyperalgesia after discontinuation of the treatment. CONCLUSION: Hyperalgesia
      induced by NP contact with the DRG can be reduced through administration of anti
      inflammatory and analgesic drugs, but a greater reduction was observed with the
      administration of dexamethasone.

PMID- 27026967
TI  - HIP FRACTURE: POST-OPERATIVE EVALUATION OF CLINICAL AND FUNCTIONAL OUTCOMES.
AB  - OBJECTIVE: To evaluate the clinical and functional outcomes from patients
      undergoing surgery to treat hip fractures, with regard to the ASA score and time
      spent waiting for definitive surgical treatment. METHOD: Over a one-year period,
      154 patients with hip fractures, aged 65 years and over, underwent operations.
      Data on the preoperative ASA score and the time spent waiting for the operation
      were obtained. Two years after the operation, Zuckerman's Functional Recovery
      Score (FRS) questionnaire was used to assess the patients' current functional
      capacity. RESULTS: Mortality during the first postoperative year differed between
      patients with ASA 3 or 4 and those classified as ASA 1 or 2 (significant data; p
      < 0.05). Mortality up to the end of the second postoperative year was
      significantly higher (p < 0.05) in the ASA 3 or 4 group. The preoperative ASA
      score did not demonstrate any significant relationship with the patients' current
      functional capacity (p > 0.05). There was no significant difference between the
      group operated within 48 hours of admission and the group operated after 48
      hours, in relation to mortality or current functional capacity (p > 0.05). The
      group aged 80 years and over showed significantly higher mortality (p < 0.05)
      than the group aged 65 to 79 years up to the end of the second postoperative
      year. CONCLUSION: The preoperative ASA score and an age of 80 years or over may
      be considered to be factors associated with higher mortality two years after hip
      fracture surgery. In isolation, time spent waiting for surgery was not
      significant.

PMID- 27026968
TI  - SURGICAL TREATMENT OF UNSTABLE PELVIC RING FRACTURE IN SKELETALLY IMMATURE
      PATIENTS.
AB  - OBJECTIVES: To present the outcomes from definitive surgical treatment for
      unstable fractures of the pelvic ring in children undergoing surgical reduction
      and stabilization. METHODS: We studied 10 patients with immature skeletons who
      suffered unstable fractures of the pelvic ring and were treated between March
      2004 and January 2008. The study was retrospective, based on clinical and
      radiographic evaluations. RESULTS: The mean age at the time of the trauma was 8.8
      years (2 to 13 years). Seven patients were female and three was male. There were
      eight cases of trauma caused by being run over, and one case each of a motorcycle
      accident and falling from a height. Five patients had other associated injuries
      such as fractures of the clavicle, femoral diaphysis, proximal humerus, lower leg
      bones, olecranon and bladder injury. All the patients evaluated showed an
      excellent clinical outcome. The pelvic asymmetry before surgery ranged from 0.7
      to 2.9 cm (mean 1.45 cm), and dropped to values between 0.2 and 0.9 cm (mean 0.39
      cm) after reduction. In no case was any change observed in pelvic asymmetry
      measured in the immediate postoperative period and at the end of follow-up.
      CONCLUSION: Pelvic ring fractures in skeletally immature patients are rare and
      surgical treatment is unusual. Several authors have questioned conservative
      treatment because of the complications encountered. Bone remodeling does not seem
      enough to cause an improvement in pelvic asymmetry, and this justifies the choice
      of surgical treatment for reduction and correction of pelvic ring deformities.

PMID- 27026969
TI  - DISTAL RADIAL FRACTURES IN PATIENTS OVER 60 YEARS OLD: ORTHOGONAL PLATES VERSUS
      VOLAR PLATE.
AB  - OBJECTIVE: To compare the results from surgical treatment between volar plates
      with angular stability and orthogonal plates in unstable distal radius fractures,
      in patients aged over 60 years. METHODS: The patients were divided into two
      groups that were treated with volar plates or orthogonal plates. Clinical and
      radiographic results were analyzed prospectively. RESULTS: The study groups
      presented similar clinical and radiographic results six months after the
      operation. However, three months after the surgery, the volar plate group had
      superior results. CONCLUSION: Both group presented good functional results.
      Surgical treatment enabled early rehabilitation. The orthogonal plate technique
      required a longer learning curve, presented more complications and worse initial
      results.

PMID- 27026970
TI  - COMPARATIVE STUDY BETWEEN THE PUBIS OF ASYMPTOMATIC ATHLETES AND NON-ATHLETES
      WITH MRI.
AB  - OBJECTIVE: To compare the magnetic resonance imaging findings from the pubis of
      professional soccer players without any history or clinical findings of groin
      pain, and from sedentary individuals, also without symptoms, and to determine the
      prevalence of changes compatible with pubic overload. METHODS: Nineteen
      professional soccer players without complaints of groin pain and seventeen
      sedentary individuals, also asymptomatic, underwent magnetic resonance imaging of
      the pubis. The results from the examinations were analyzed regarding the presence
      of degenerative changes, boned medullary edema and tendinopathy, and the two
      study groups were compared. RESULTS: High prevalence of bone edema, tendinopathy
      and degenerative findings in the pubic symphysis was seen in the athletes, with
      statistically significant higher odds ratios and relative risk in the population
      studied. CONCLUSION: Professional soccer players are at a higher risk of
      developing changes in the pubic region, shown in magnetic resonance images,
      compared with sedentary individuals. These findings are not necessarily caused by
      groin pain, and are probably related to intense exertion.

PMID- 27026971
TI  - RANDOMIZED CONTROLLED TRIALS IN ORTHOPEDICS AND TRAUMATOLOGY: SYSTEMATIC ANALYSIS
      ON THE NATIONAL EVIDENCE.
AB  - OBJECTIVE: To assess whether there has been any improvement in the quality and
      quantity of randomized controlled trials (RCTs) in nationally published journals
      through the application of standardized and validated scores. METHODS: We
      electronically selected all RCTs published in the two indexed Brazilian journals
      that focus on orthopedics, over the period 2000-2009: Acta Ortopedica Brasileira
      (AOB) and Revista Brasileira de Ortopedia (RBO). These RCTs were identified and
      scored by two independent researchers in accordance with the Jadad scale and the
      Cochrane Bone, Joint and Muscle Trauma Group score. The studies selected were
      grouped as follows: 1) publication period (2000-2004 or 2004-2009); 2) journal of
      publication (AOB or RBO). RESULTS: Twenty-two papers were selected: 10 from AOB
      and 12 from RBO. No statistically significant differences were found between the
      proportions (nRCT/nTotal of published papers) of RCTs published in the two
      journals (p = 0.458), or in the Jadad score (p = 0.722) and Cochrane score (p =
      0.630). CONCLUSION: The relative quality and quantity of RCTs in the journals
      analyzed were similar. There was a trend towards improvement of quality, but
      there was no increase in the number of RCTs between the two periods analyzed.

PMID- 27026972
TI  - RECONSIDERATIONS REGARDING TIME OF FRACTURE HEALING IN PYCNODYSOSTOSIS.
AB  - OBJECTIVE: To discuss what has been described so far in the literature regarding
      the time taken for fracture consolidation in pycnodysostosis. MATERIALS AND
      METHODS: Thirteen new cases were studied, as available from the medical records
      and radiographic examinations, thus encompassing a total of 44 fractures in
      patients evaluated between November 1970 and August 2004 at the Orthopedics
      Hospital, Goiania. Field research, simultaneous clinical monitoring for new
      fractures in two patients and retrospective evaluation of medical records were
      undertaken. The purpose was to determine the total number of fractures in each
      patient and to determine which of these were viable for this study. The patient
      group was composed of three women and two men of mean age 51.4 years. The tibia
      was the bone most affected, followed by the femur. Fractures for which the follow
      up was done at another clinic were excluded. RESULTS: Out of the 12 fractures
      that were considered fully suitable for the study, nine occurred in femurs (six
      in the left femur and three in the right femur); one in the right tibia; one in
      the right clavicle; and one in the left ulna. Among these 12 fractures, eight
      developed pseudarthrosis after an average of 29.25 months; three consolidated
      well after an average of 5.83 months; and one evolved with delayed consolidation
      in just 2 months. CONCLUSION: In combination with genetic and micromorphological
      evaluations, further studies are awaited for reconfirmation of the diagnosis of
      such a rare clinical entity.

PMID- 27026973
TI  - CEMENTLESS ENDOPROSTHESIS IN THE TREATMENT OF GIANT CELL TUMOR OF THE TIBIA:
      EIGHTEEN YEARS OF EVOLUTION.
AB  - This is a case report on a giant cell tumor of the juxta-articular proximal tibia
      with a pathological fracture. A female patient presented pain and increased local
      volume after falling from her own height. She underwent clinical examination,
      radiographic examination and puncture biopsy. A diagnosis of giant cell tumor was
      made. The patient was then treated with tumor resection and use of an
      unconventional partial endoprosthesis of the tibia with preservation of the joint
      surface of the tibial plateau. The patient evolved with improvement of symptoms
      and maintenance of joint function of the operated limb, absence of recurrence and
      complications, without any need for reoperation over 18 years of follow-up. 

PMID- 27026974
TI  - GORHAM-STOUT SYNDROME: PHANTOM BONE DISEASE.
AB  - Gorham-Stout syndrome is a disease that presents idiopathic osteolysis of a bone
      or closely contiguous area. The etiology is unknown. It is a rare condition that
      is difficult to diagnose, and its treatment is controversial. It affects
      individuals irrespective of age or sex. In this study, we conducted a
      bibliographic review of the disease, specifically focusing on the differential
      diagnosis, and we demonstrated the follow-up on a patient with this syndrome from
      the time of its diagnosis, through treatment, to its current state of evolution. 

PMID- 27026975
TI  - GUYON'S CANAL SYNDROME DUE TO A SYNOVIAL CYST.
AB  - We present a case of Guyon's canal syndrome caused by a synovial cyst within the
      left wrist of a 48-year-old female patient. The patient presented pain and
      paresthesia in the region of the ulnar nerve, with loss of muscle strength and
      left-hand deformity. Electroneuromyography showed a compression of the ulnar
      nerve at the wrist level. Surgical decompression of the nerve at Guyon's canal
      with resection of the cyst was performed. After the surgery, the patient
      presented an improvement in the pain and paresthesia, as well as an increase in
      muscle trophism and correction of the deformity. 

PMID- 27026976
TI  - PRE-OPERATIVE PLANNING AND SURGICAL TECHNIQUE OF THE OPEN WEDGE SUPRACONDYLAR
      OSTEOTOMY FOR CORRECTION OF VALGUS KNEE AND FIXATION WITH A FIXED-ANGLE IMPLANT.
AB  - The step-by-step preoperative planning for supracondylar opening wedge osteotomy
      of the femur for precise correction of the load axis of the lower limb using a
      fixed-angle implant (95 degrees  AO blade plate) is presented. The surgical
      technique and the use of a bone graft from the same site for filling in the
      defect are also presented. 

PMID- 27026977
TI  - THE FIRST VOLUME OF THE RBO IN 1939 AND THE OBSTINACY OF ACHILLES DE ARAUJO.

PMID- 27026978
TI  - GENESIS OF PAIN IN ARTHROSIS.
AB  - Advances in knowledge regarding the pathophysiology of pain among patients with
      knee osteoarthritis suggest that the central nervous system is involved as a
      source that maintains and amplifies the painful condition such that it is
      refractory to conventional orthopedic and rheumatological treatment. Initially,
      hyperalgesia is observed only at the affected site. However, when the pain
      becomes refractory, peripheral and central sensitization mechanisms contribute
      towards maintaining and amplifying the painful conditions, regardless of the
      peripheral process that originated the pain. At this stage, even removal of the
      etiological agent may no longer be enough to relieve the painful symptoms. It
      then becomes necessary to envisage that other factors, distant from the affected
      joint, may be responsible for the disabling painful condition in such patients.
      At present, osteoarthrosis does not have any known cure, and the aim of treatment
      is to lessen the pain while improving function and health-related quality of
      life, and whenever possible, to minimize the toxicity of the therapy. In the
      light of emerging evidence suggesting that the central nervous system has a role
      in the physiopathology of pain in patients with knee arthrosis, the central
      nervous system should be taken into consideration as a therapeutic target,
      instead of only administering local treatment using ordinary analgesics, anti
      inflammatory drugs and non-pharmacological measures. Thus, methods that modulate
      the spinal cord and cerebral cortex, including the use of antidepressants, may
      have a role in managing these patients. 

PMID- 27026979
TI  - NAVIGATION IN TOTAL KNEE ARTHROPLASTY.
AB  - Navigation was the most significant advance in instrumentation for total knee
      arthroplasty over the last decade. It provides surgeons with a precision tool for
      carrying out surgery, with the possibility of intraoperative simulation and
      objective control over various anatomical and surgical parameters and references.
      Since the first systems, which were basically used to control the alignment of
      bone cutting referenced to the mechanical axis of the lower limb, many other
      surgical steps have been incorporated, such as component rotation, ligament
      balancing and arranging the symmetry of flexion and extension spaces, among
      others. Its efficacy as a precision tool with an effective capacity for promoting
      better alignment of the lower-limb axis has been widely proven in the literature,
      but the real value of optimized alignment and the impact of navigation on
      clinical results and the longevity of arthroplasty have yet to be established. 

PMID- 27026980
TI  - EPIDEMIOLOGICAL ANALYSIS ON ACETABULAR FRACTURES.
AB  - This aim of this work was to carry out an epidemiological study on acetabular
      fractures in the city of Campinas and surrounds, in view of the few published
      papers on this subject. Medical files with a diagnosis of acetabular fracture
      between the years 2004 and 2008 that were made available by the Medical Archiving
      Service of Hospital das Clinicas, State University of Campinas (UNICAMP) were
      analyzed by six observers. Data on patients' ages, sex, side affected by the
      fracture, mechanism of injury, material used for synthesis, complications of the
      operation, associated fractures, length of hospitalization before and after the
      surgery, time of total internment and number of physiotherapy sessions before and
      after the surgery were gathered. It was observed in this population that the left
      side was more affected; the mechanism of injury that most often caused this type
      of fracture was automobile accidents; injuries to the sciatic nerve were the
      commonest surgical complications; and the synthesis material most used was
      reconstruction plates. 

PMID- 27026981
TI  - USE OF AUTOLOGOUS BONE GRAFT ASSOCIATED WITH SUPPORT OSTEOSYNTHESIS FOR TIBIAL
      EDGE BONE LOSSES IN TOTAL KNEE PROSTHESES.
AB  - OBJECTIVE: To report the initial results from the use of a new technique for
      fixation of bone grafts in uncontained tibial bone defects in patients undergoing
      total knee prosthesis implantation. METHODS: Six patients with severe varus
      deformity of the knee who, after cuts and ligament balancing had been performed,
      still presented bone deficiencies that reached the edge of the tibial cut and
      compromised the implant stability, underwent a new fixation technique. RESULTS:
      Five of the patients had good-clinical results, with integration of the graft
      within 12 weeks. One patient presented clinical complications with wound
      dehiscence and implant exposure, which evolved to the need for implant removal
      and knee arthrodesis. CONCLUSION: Support osteosynthesis as a graft fixation
      method is a viable option for treating tibial bone deficiencies. The proposed
      technique certainly needs further studies for its validation.

PMID- 27026982
TI  - DOUBLE-BUNDLE ANATOMICAL RECONSTRUCTION OF THE ANTERIOR CRUCIATE LIGAMENT: A
      PROSPECTIVE STUDY WITH TWO-YEAR FOLLOW-UP.
AB  - OBJECTIVE: To prospectively evaluate the results from double-bundle
      reconstruction of the anterior cruciate ligament, among patients at our clinic,
      by means of the 2000 protocol of the International Knee Documentation Committee
      (IKDC). STUDY DESIGN: Case series; level of evidence IV. METHODS: Fifty-eight
      patients who underwent anatomical reconstruction of the anterior cruciate
      ligament using an autologous flexor tendon graft by means of the double-bundle
      technique were evaluated in accordance with the IKDC 2000 protocol. The patients'
      ages ranged from 17 to 58 years, with a mean of 35.2 years. The follow-up ranged
      from 24 to 37 months (mean of 28.9 months). RESULTS: Postoperatively, 89.65% of
      the pivot-shift test findings were negative. In the final evaluation, 44 (75.86%)
      of the patients' knees were graded as normal, 13 (22.41%) as nearly normal and
      one (1.72 %) as abnormal. CONCLUSION: The technique used was effective in
      promoting restoration of joint stability, without compromising mobility.

PMID- 27026983
TI  - PERI-INCISIONAL DYSESTHESIA FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION
      USING CENTRAL THIRD OF PATELLAR TENDON.
AB  - OBJECTIVE: To evaluate the prevalence and type of dysesthesia around the incision
      used to obtain the patellar tendon for anterior cruciate ligament (ACL)
      reconstruction surgery. METHODS: Out of a population of 1368 ACL reconstructions
      using the central third of the patellar tendon, 102 patients (111 knees) were
      evaluated by means of telephone interview. RESULTS: The mean follow-up was 52
      months (ranging from 12 to 88 months). The patients' ages ranged from 16 to 58
      years (mean: 34.7 years). There was some degree of peri-incisional dysesthesia in
      66 knees (59.46%). In 40.54% of the knees, this condition was not found. In all
      the cases of dysesthesia, the type encountered was Highet's type II. CONCLUSION:
      Peri-incisional dysesthesia following ACL reconstruction using the central third
      of the patellar tendon is highly prevalent. It affected more than half of the
      cases in this series.

PMID- 27026984
TI  - INFLUENCE OF ANTERIOR PAIN ON RESULTS FROM ANTERIOR CRUCIATE LIGAMENT
      RECONSTRUCTION.
AB  - OBJECTIVE: To examine the impact of residual pain on functional outcomes two
      years after arthroscopic anterior cruciate ligament (ACL) reconstruction and
      compare the types of graft used during the procedure (patellar vs. flexor).
      METHOD: A retrospective epidemiological study on 129 ACL reconstructions with a
      mean follow-up of 28 months was conducted. The presence, intensity and location
      of the anterior pain were investigated. Pain provocation tests were conducted,
      sensitivity was analyzed and functional scores were applied (IKDC, femoropatellar
      and SF-36), comparing the results with the type of graft used. RESULTS: Anterior
      pain was present in 28% of patients with a mean intensity of 2.9 in 10. When pain
      was present, the functional scores decreased significantly. Abnormalities of knee
      sensitivity and gait occurred frequently with use of the patellar tendon, but
      there was no statistical difference regarding the presence of pain. CONCLUSION:
      The presence of anterior pain in ACL reconstructions, even if minimal, has a
      deleterious effect on the final outcome over the medium term. Because of the
      influence of graft harvesting on the presence of abnormalities of knee
      sensitivity and gait, choosing the graft should take into account the patient's
      professional and sports activities.

PMID- 27026985
TI  - EVALUATION OF THE RESULTS FROM REOPERATIONS ON PATIENTS WITH ROTATOR CUFF
      LESIONS.
AB  - OBJECTIVES: To assess the results from open or arthroscopic surgical treatment on
      patients with symptomatic recurrence of rotator cuff injuries. METHODS: Between
      December 1990 and July 2007, 30 patients were assessed and underwent reoperation
      performed by the Shoulder and Elbow Surgery Group of the Department of
      Orthopedics and Traumatology, Fernandinho Simonsen Wing, Santa Casa de Sao Paulo,
      because of dehiscence of the rotator cuff suture. The study included patients
      with symptomatic recurrence of the injury and with at least 24 months of
      postoperative follow-up. RESULTS: According to the UCLA evaluation criteria, 21
      patients (70%) showed excellent or good outcomes; and nine patients (30%) showed
      fair or poor outcomes. CONCLUSION: Open or arthroscopic surgical treatment of
      recurrent rotator cuff injuries tended to present worse results than from the
      primary repair. In this study, we found that 70% of the results were excellent
      and good. The presence of extensive injuries in the reoperation tended to evolve
      with larger numbers of unsatisfactory results. In our study, we obtained better
      results from arthroscopic surgery than from open surgery.

PMID- 27026986
TI  - EVALUATION OF RESULTS AND COMPLICATIONS FROM ARTHROSCOPIC SUTURE OF SLAP LESIONS.
AB  - OBJECTIVE: To evaluate the results and complications from arthroscopic suturing
      of SLAP lesions. METHODS: Seventy-one patients who underwent arthroscopic
      suturing of SLAP lesions between July 1995 and May 2008 were evaluated. The
      procedures were performed by the Shoulder and Elbow Surgery Group of the
      Department of Orthopedics and Traumatology, Fernandinho Simonsen Wing, Santa Casa
      de Sao Paulo, Brazil. Associated lesions were seen in 68 of the 71 patients
      evaluated (96%), and the other three (4%) had SLAP lesions alone. RESULTS: The
      associated lesions most frequently found in the patients under 40 years of age
      were labral lesions (69%), while in patients aged 40 years or over, impact
      syndrome with or without rotator cuff injury was the most commonly associated
      condition (71.4%). According to the UCLA method, 79% of our results (56 cases)
      were good or excellent. Postoperative complications occurred in 15 cases (21%);
      among these, the most common was the presence of residual pain (46.6%), followed
      by adhesive capsulitis (33.3%). CONCLUSIONS: There was a great association
      between SLAP lesions and other shoulder lesions, which varied according to the
      patients' age groups. Arthroscopic suturing of the SLAP lesions provided
      excellent results in the majority of the cases, but complications occurred in
      21%.

PMID- 27026987
TI  - COMPARISON OF THE FEMORAL HEAD HEIGHT/NECK LENGTH RATIO BETWEEN THE UNAFFECTED
      HIP OF PATIENTS WITH A UNILATERAL SLIPPED FEMORAL HEAD AND THE HIPS OF
      INDIVIDUALS WITHOUT A SLIPPED FEMORAL HEAD.
AB  - Objective - To compare the head/neck ratio on the contralateral side of patients
      with a unilateral slipped capital femoral epiphysis (SCFE) with control
      individuals. Methods - Seventeen patients who were followed up at the Department
      of Orthopedics and Traumatology, Federal University of Sao Paulo, Brazil, between
      1985 and 2007, were assessed. The control group consisted of 34 individuals from
      the same place who were matched for gender and age, with a history of trauma that
      necessitated pelvic radiography. The femoral head height and femoral neck
      measurements were made using simple pelvic radiography in accordance with the
      criteria of Bleck (1983), on both sides in the control group and on the
      contralateral hip in the patients. Nonparametric statistics were used, with a p
      value <= 0.05. Results - There was no difference in the distribution of age,
      gender, body mass index and bone age between the groups. The head/neck ratio on
      the right and left side in the controls did not differ (p = 0.64). However, the
      head/neck ratio from the contralateral hip of the patients with SCFE was
      significantly lower than that of the control group (p = 0.00). Conclusion - The
      significantly lower head/neck ratio in the patients with epiphysiolysis could be
      indicative of a risk of SCFE. 

PMID- 27026988
TI  - COMPLICATIONS FOLLOWING MEDIAL OPENING WEDGE OSTEOTOMY OF THE KNEE: RETROSPECTIVE
      STUDY.
AB  - OBJECTIVE: To retrospectively survey the most frequent complications from medial
      opening wedge high-tibial osteotomy. This procedure is becoming increasingly
      important in treating knee arthrosis, as one of the options for young and active
      patients. Despite satisfactory results and its benefits, it is not a complication
      free procedure. METHODS: All cases of medial opening wedge high-tibial osteotomy
      above the tibial tubercle with fixation using a Puddu plate that were performed
      at the Celso Pierro Hospital and Maternity Hospital, Pontifical Catholic
      University of Campinas (PUC-Campinas) and the Wilson Mello Institute, Campinas,
      between October 1, 1987, and October 30, 2008, were evaluated retrospectively.
      Patients with less than 12 months of follow-up or incomplete medical files, and
      those who underwent bilateral osteotomy, were excluded. RESULTS: Out of the 67
      cases evaluated, 55 were males and 12 were females, with a mean age of 49.5
      years. The mean wedge size was 10.15 mm and the most common complications were
      moderate to severe pain (13.04%), stiffness (6.52%), material breakage (4.4%),
      intraoperative fracture of the lateral cortical bone (4.4%) and infection (4.4%).
      It was observed that patients with delayed consolidation of the osteotomy had a
      greater chance of presenting complications (p < 0.05). CONCLUSION: Complications
      from medial wedge osteotomy are more frequent when associated with delayed
      consolidation.

PMID- 27026989
TI  - FEMORAL ANTEVERSION AND THE NECK-SHAFT ANGLE: RELATIONSHIP WITH HIP
      OSTEOARTHRITIS.
AB  - OBJECTIVE: To compare the existence of agreement between measurements of
      anteversion of the femoral neck and the degrees of osteoarthritis and abnormality
      of the neck-shaft angle in patients with unilateral idiopathic hip
      osteoarthritis, among three evaluators. METHODS: Forty-two patients with
      unilateral hip osteoarthritis were evaluated by means of simple radiography and
      computed tomography. RESULTS: It was observed that there was no significant
      variation in femoral anteversion between the diseased and healthy hips. There was
      strongest agreement between observers 1 and 2 in relation to both the diseased
      hips (cases) and the healthy hips (controls). Moreover, no significant agreement
      was found between observers 1 and 3 (p = 0.13) and between observers 2 and 3 (p =
      0.12), in relation to the neck-shaft angle of the control hips. CONCLUSION:
      Although there was no relationship between femoral anteversion and the neck-shaft
      angle in the patients with unilateral hip osteoarthritis, the present study
      showed that there was also no relationship with these angular deviations.

PMID- 27026990
TI  - ARTHROPLASTY FOR TRAPEZIUM EXCISION AND TENDON INTERPOSITION IN RHIZARTHROSIS
      CASES: PROSPECTIVE STUDY.
AB  - OBJECTIVE: To prospectively evaluate the results from a series of patients who
      underwent surgical treatment for rhizarthrosis using the technique of trapezium
      resection associated with interposition of yarn from the long abductor tendon of
      the thumb. METHODS: From May to August 2005, ten patients underwent surgical
      treatment for rhizarthrosis. Patients with primary osteoarthrosis of the
      trapezium-metacarpal joint, in stages II, III and IV of the Eaton classification,
      with persistent pain that was refractory to clinical treatment, were included.
      For the functional assessment, the visual analogue scale, DASH questionnaire and
      Buck-Gramcko score were used. For the overall assessment on the patients,
      strength measurements were made for palm grip, pulp to pulp pinch, lateral pinch,
      three-point pinch, opposition and radial and palmar abductions. The migration
      index for the first metacarpal was also determined on radiographs at rest and
      under stress. RESULTS: The pain relief was considered to be good (p = 0.005),
      with functional improvements in modules 2 (p = 0.02) and 3 (p = 0.022) of DASH.
      The Buck-Gramcko score showed one excellent and three very good results. There
      was an improvement in almost all of the overall assessment and was only non
      significant regarding lateral pinch and abduction. For all patients, there was
      migration of the first metacarpal. CONCLUSION: Trapeziectomy associated with
      interposition of yarn from the long abductor tendon of the thumb was shown to be
      a relatively simple and effective technique for pain relief and functional
      improvement.

PMID- 27026991
TI  - SURGICAL TREATMENT OF RHIZARTHROSIS: TRAPEZIECTOMY WITH OR WITHOUT
      LIGAMENTOPLASTY VERSUS TOTAL PROSTHESIS.
AB  - OBJECTIVE: The aim of this study was to review cases that underwent surgical
      treatment using two techniques: trapeziectomy with or without ligamentoplasty and
      arthroplasty with implant. METHODS: Fifty-two hands that were surgically treated
      for rhizarthrosis between 1995 and 2008 were evaluated: 32 cases of trapeziectomy
      with or without ligamentoplasty (group A) and 20 with implant arthroplasty (group
      B). The mean follow-up for group A was 72 months and for group B, 23 months.
      There were no significantly different results with regard to pain, activities of
      daily living, mobility or strength. In the radiographic evaluation, it was found
      that the scaphometacarpal height was better preserved in group B. The mean time
      taken to achieve recovery was 10 weeks in group A and 4.5 in group B. Four cases
      with complications were recorded: one case of algoneurodystrophy in group A and
      two cases of dislocation and one case of fracture of the trapezium in group B.
      RESULTS: The results from prostheses were better than the results from the
      traditional treatment for rhizarthrosis using trapeziectomy with or without
      ligamentoplasty because of the rapid recovery that prostheses provide.
      CONCLUSION: However, prostheses should be applied carefully, because there is a
      potential for complications relating to the implants.

PMID- 27026992
TI  - SPONTANEOUS RESOLUTION OF PSEUDOANEURYSM OF AN ILIAC ARTERY BRANCH IN A MULTIPLE
      TRAUMA PATIENT WITH PELVIC FRACTURE: CLINICAL CASE.
AB  - In patients who have been the victims of high-energy trauma, severe pelvic injury
      should always be suspected. Most of these fractures are stable and respond well
      to conservative treatment. Pelvic fractures constitute 3% of all skeletal
      fractures and are associated with high-energy trauma. They are potentially
      serious injuries with significant mortality and large numbers of associated
      lesions. There are fundamentally three sources of bleeding in pelvic fractures:
      arterial, venous and through the bone ends of the fracture. Arterial bleeding is
      more associated with hemodynamic instability. In such cases, both early external
      fixation of the pelvic fracture and angiography with selective embolization of
      the bleeding vessels are effective methods for achieving hemostasis. Aneurysms of
      iliac artery branches are rare and are mostly pseudoaneurysm relating to the
      traumatic event. The natural history of pseudoaneurysms is unknown because of
      their rarity, but if they rupture, the mortality rate is high. We report a case
      of spontaneous thrombosis of a pseudoaneurysm of a branch of the right iliac
      artery. 

PMID- 27026993
TI  - THIRD-DEGREE BURN IN THE REGION OF THE ELECTROSURGICAL PAD DURING SHOULDER
      ARTHROSCOPY: A CASE REPORT.
AB  - The number of shoulder arthroscopy procedures is increasing and, because of this,
      the frequency of related complications is also increasing. This report presents a
      case of third-degree burn from an electrosurgical pad during this procedure and
      serves as an alert regarding the possible causes and how to try to prevent this
      rare, but possible complication. 

PMID- 27026994
TI  - HYBRID ANKLE PROSTHESIS IN A CASE OF POST-TRAUMATIC AVASCULAR NECROSIS OF THE
      TALUS.
AB  - Talus fractures often lead to late post-traumatic arthrosis. In such cases, the
      use of latest generation, cementless prostheses has been hindered by the presence
      of avascular necrosis. We report the case of a 65-year-old patient who presented
      four years after a talus neck fracture. He had painful ankle arthrosis (AOFAS
      ankle-hindfoot score 19) and avascular necrosis, with collapse of the entire
      talar dome. Given the extent of the necrosis, it was decided to cement the talus
      prosthetic component. One year after the surgery, the patient shows good clinical
      and radiological results (AOFAS ankle-hindfoot score 87) and is satisfied with
      the procedure. We are not aware of any similar reports in the literature. 

PMID- 27026995
TI  - PYOMYOSITIS IN ATHLETES AFTER THE USE OF ANABOLIC STEROIDS - CASE REPORTS.
AB  - OBJECTIVE: To report on the management of five cases of pyomyositis in athletes
      after the use of anabolic steroids. METHOD: Over the past 10 years, five cases of
      athletes who developed pyomyositis after using anabolic steroids were attended at
      the Sports Trauma Center (CETE), EPM-UNIFESP. RESULTS: All the patients were
      diagnosed clinically and through laboratory and imaging tests. Surgical treatment
      was carried out (with collection of material for culturing) and antibiotic
      therapy was administered. In four cases, the injection sites were in the upper
      limbs and in one case, in the gluteus muscles bilaterally as well as in the upper
      limbs. In all five cases, occurrences of leukocytosis and neutrophilia were
      observed in the hemogram. After debridement, the germs of normal skin (S. aureus
      and S. viridans) were found in cultures on the secretions. Demarcation of the
      abscess and examination of the muscle plane in which the abscess was located were
      performed using ultrasound and magnetic resonance imaging. All the patients
      responded to broad-spectrum antibiotic therapy. Two cases required more than one
      surgical procedure because of the appearance of more than one abscess site with
      different evolution times. CONCLUSION: The use of anabolic steroids by some
      athletes may have grave consequences. Rapid, energetic and multidisciplinary
      intervention is necessary in such cases in order to avoid undesirable results.
      The right treatment healed the athletes completely, and they returned to their
      sports at the same level.

PMID- 27026996
TI  - EXCISION OF GIANT CELL TUMOR OF TENDON SHEATH WITH BONE INVOLVEMENT BY MEANS OF
      DOUBLE ACCESS APPROACH: CASE REPORT.
AB  - Giant cell tumors of the tendon sheath are common lesions and are the second most
      frequent tumors in the hand, after synovial cysts. They are diagnosed by means of
      clinical examination and complementary examinations (simple radiography and
      magnetic resonance). Erosion and invasion of the phalangeal bone affected may be
      seen on radiological examination. Magnetic resonance may show a "fluorescent or
      radiant effect" may be observed, caused by the high quantity of hemosiderin
      inside the tumor. Surgical treatment is the commonest practice, and complete
      excision is important for avoiding recurrence of the tumor, especially when bone
      invasion is observed on imaging examinations, which is generally related to
      greater tumor recurrence. In this paper, a case of a giant cell tumor of the
      tendon sheath in the middle phalanx of the third finger of a 45-year-old female
      patient is presented. This was successfully treated by means of surgery using a
      double access approach (dorsal and volar). 

PMID- 27026997
TI  - BILATERAL ANTERIOR PELVIC OSTEOTOMY FOR OLOSURE OF BLADDER EXSTROPHY: DESCRIPTION
      OF TECHNIQUE.
AB  - Bladder and cloacal exstrophy are rare malformations associated with
      abnormalities in the pelvis. The objectives in reconstruction are to obtain a
      closed and continent bladder, with an acceptable cosmetic appearance. Treatment
      for the abnormalities of pelvic anatomy is an important part of achieving
      successful treatment for these urological conditions. This article aims to
      describe the technique of bilateral anterior pelvic osteotomy for treating
      bladder and cloacal exstrophy, and presents two cases to demonstrate the
      difficulties and applications of the technique. 

PMID- 27026998
TI  - LEGG-CALVE-PERTHES DISEASE: 100 YEARS.

PMID- 27026999
TI  - TIBIAL SHAFT FRACTURES.
AB  - The long-bone fractures occur most frequently in the tibial shaft. Adequate
      treatment of such fractures avoids consolidation failure, skewed consolidation
      and reoperation. To classify these fractures, the AO/OTA classification method is
      still used, but it is worthwhile getting to know the Ellis classification method,
      which also includes assessment of soft-tissue injuries. There is often an
      association with compartmental syndrome, and early diagnosis can be achieved
      through evaluating clinical parameters and constant clinical monitoring. Once the
      diagnosis has been made, fasciotomy should be performed. It is always difficult
      to assess consolidation, but the RUST method may help in this. Radiography is
      assessed in two projections, and points are scored for the presence of the
      fracture line and a visible bone callus. Today, the dogma of six hours for
      cleaning the exposed fracture is under discussion. It is considered that an early
      start to intravenous antibiotic therapy and the lesion severity are very
      important. The question of early or late closure of the lesion in an exposed
      fracture has gone through several phases: sometimes early closure has been
      indicated and sometimes late closure. Currently, whenever possible, early closure
      of the lesion is recommended, since this diminishes the risk of infection.
      Milling of the canal when the intramedullary nail is introduced is still a
      controversial subject. Despite strong personal positions in favor of milling,
      studies have shown that there may be some advantage in relation to closed
      fractures, but not in exposed fractures. 

PMID- 27027000
TI  - FLUOROSCOPY DURATION IN ORTHOPEDIC SURGERY.
AB  - OBJECTIVE: To ascertain the mean length of radiation emission from fluoroscopic
      devices during several types of orthopedic surgery and which of these required
      greater use of radiation. METHODS: The times taken to perform sixteen different
      types of surgery (total of 80 procedures) were measured. At the end of each
      procedure, the length of time for which fluoroscopy was used directly from the
      image intensifier was ascertained. RESULTS: The mean time required for
      fluoroscopy per operation was 61 seconds. The procedures that demanded greatest
      mean duration of radiation use were bilateral proximal femoral epiphysiodesis
      (5.1 minutes) and femoral shaft osteosynthesis using a locked intramedullary nail
      (3.33 min). CONCLUSION: The mean duration of fluoroscopy use in orthopedic
      operations was 61 seconds. The procedures using an intramedullary device were the
      ones that required greatest radiation emission.

PMID- 27027001
TI  - CORRELATION BETWEEN CALCANEAL BONE ULTRASOUND MEASUREMENTS AND DENSITOMETRY AMONG
      POSTMENOPAUSAL WOMEN WITH FRACTURES CAUSED BY BONE FRAGILITY.
AB  - OBJECTIVE: To assess the correlation between ultrasound (US) measurement on the
      calcaneus and bone densitometry (DEXA), among postmenopausal women who already
      presented fragility fractures. METHODS: 35 postmenopausal women over 40 years of
      age, with the ability to walk and presenting osteoporotic fractures of the wrist
      or spine, without previous treatment for osteoporosis, were analyzed in a
      retrospective cohort. Of these, 16 were under 60 and 19 were over 60. The
      broadband ultrasound attenuation (BUA) and speed of sound (SOS) were compared
      using DEXA (L1-L4, total femur, femoral neck and wrist). Two different values of
      BUA were used as cutoff points for osteoporosis: BUA < 60 dB/MHz and BUA < 64
      dB/MHz (P < 0.05); and SOS < 1600 m/s. The confidence interval was 95%. The DEXA
      and US data were plotted on dispersion graphs and, through linear regression, it
      was possible to establish correlations. Following this, the sample was stratified
      according to age (up to 60 years and 60 years and over). Thus, the values were
      again compared and correlated. RESULTS: The best correlation obtained between
      DEXA and US was between the T-score of the wrist and BUA < 64 dB/MHz, with 92%
      sensitivity and 95% specificity. Better sensitivity at all DEXA sites was
      obtained when US was performed on patients over 60 years of age. The SOS
      compatible with osteoporosis was < 1592.5 m/s (89% sensitivity and 85%
      specificity). CONCLUSION: US on the calcaneus can be used for screening the risk
      of osteoporosis fractures, using a cutoff of BUA < 64 dB/MHz, especially among
      patients over 60 years of age.

PMID- 27027002
TI  - EVALUATION OF THE RESULTS OF ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION USING
      FLEXOR TENDONS AND RIGID GUIDE TRANSVERSE SCREW.
AB  - OBJECTIVE: The aim of this study was to analyze the results of ACL (anterior
      cruciate ligament) reconstruction using quadruple flexor tendons as grafts, with
      ligament fixation in the femur using a rigid guide transverse screw and in the
      tibia, using a cancellous screw with a fixing washer. METHODS: 173 knees (166
      from males and seven from females) that had undergone surgery with ACL
      reconstruction using this technique between December 2002 and February 2007 were
      evaluated. The mean age was 30 years (from 13 to 56 years), and the mean follow
      up time was 30 months (6-55 months). We divided the knees into three groups,
      which were assessed using the Lysholm scale: Group A with six months of follow
      up; Group B with 12 months of follow-up; and Group C with 24 months of follow-up.
      RESULTS: We evaluated the results, and groups A, B and C received 94, 95 and 95
      points respectively on the Lysholm scale. CONCLUSIONS: The surgical technique
      proved to be safe and easy to perform, with good results and a low complication
      rate. Also, its results were maintained throughout the study period of 24 months.

PMID- 27027003
TI  - ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION USING THE DOUBLE-BUNDLE TECHNIQUE -
      EVALUATION IN THE BIOMECHANICS LABORATORY.
AB  - OBJECTIVE: The objective of this study was to describe the methodology of knee
      rotation analysis using biomechanics laboratory instruments and to present the
      preliminary results from a comparative study on patients who underwent anterior
      cruciate ligament (ACL) reconstruction using the double-bundle technique.
      METHODS: The protocol currently used in our laboratory was described. Three
      dimensional kinematic analysis was performed and knee rotation amplitude was
      measured on eight normal patients (control group) and 12 patients who were
      operated using the double-bundle technique, by means of three tasks in the
      biomechanics laboratory. RESULTS: No significant differences between operated and
      non-operated sides were shown in relation to the mean amplitudes of gait, gait
      with change in direction or gait with change in direction when going down stairs
      (p > 0.13). CONCLUSION: The preliminary results did not show any difference in
      the double-bundle ACL reconstruction technique in relation to the contralateral
      side and the control group.

PMID- 27027004
TI  - COMPARATIVE STUDY BETWEEN RADIOLOGICAL CLASSIFICATION AND MACRO AND MICROSCOPIC
      ANALYSIS ON OSTEOARTHRITIS LESIONS OF THE KNEE.
AB  - OBJECTIVES: To compare the modified Ahlback radiological classification with
      macroscopic analysis of knee injuries and locate a chondral lesion in the tibial
      plateau, and to correlate this with integrity or lack of integrity of the
      anterior cruciate ligament. MATERIAL AND METHODS: Between July and December 2009,
      40 patients of mean age 67.1 years with an indication for total knee arthroplasty
      were selected. The modified Ahlback radiological classification was used. The
      International Cartilage Repair Society classification was used for macroscopic
      analysis of the lesions. Chondral injuries were correlated with the integrity or
      lack of integrity of the anterior cruciate ligament. RESULTS: Regarding the
      radiological classification of the knees, three (7.5%) were classified as grade
      1, two (5%) as grade 2, 17 (42.5%) as grade 3, 16 (40%) as grade 4 and two (5%)
      as grade 5. The macroscopic analysis of the knee showed that 25 patients (62.5%)
      had very severe injury and 15 (37.5%), severe. In eight knees (20%) with ruptured
      ACL, the lesion extended to the posterior region of the medial tibial plateau.
      When the ACL was intact, the lesion was located in the anterior-central region.
      CONCLUSION: Knee osteoarthritis of grades 4 and 5 in the radiological
      classification, showed agreement with the macroscopic analysis, i.e. very severe
      chondral injury. However, grades 1, 2 and 3 were discordant. In the cases of
      osteoarthritis with intact ACL, the lesion was located in the anterior-central
      region of the medial tibial plateau, and those with ruptured ACL had the lesion
      extending to the posterior region of the plateau.

PMID- 27027005
TI  - MEDIAL PATELLOFEMORAL LIGAMENT RECONSTRUCTION TO TREAT RECURRENT PATELLAR
      DISLOCATION.
AB  - OBJECTIVE: To present a new technique for reconstruction of the medial
      patellofemoral ligament (MPFL) in patients with recurrent patellar dislocation
      and to evaluate the clinical findings from this. METHODS: Between January 2007
      and January 2008, 23 patients underwent reconstruction of the MPFL with a free
      graft from the semitendinosus tendon. After a minimum of 24 months of follow-up,
      22 patients were evaluated using the Kujala and Lysholm clinical protocols.
      RESULTS: The mean follow up was 26.2 months. According to the Lysholm protocol,
      the patients had a mean score of 53.72 points preoperatively and 93.36 points
      postoperatively (p = 0.000006). According to the Kujala protocol, the mean score
      was 59.81 points preoperatively and 83.54 points postoperatively (p = 0.002173).
      CONCLUSION: Reconstruction of the medial patellofemoral ligament using the
      proposed technique showed excellent results over the short term, when evaluated
      by means of clinical protocols.

PMID- 27027006
TI  - COMPARATIVE ANALYSIS ON THE RESULT FOR ARTHROSCOPIC ROTATOR CUFF SUTURE BETWEEN
      SMOKING AND NON-SMOKING PATIENTS.
AB  - OBJECTIVE: To comparatively analyze the results from arthroscopic rotator cuff
      suture between smoking and non-smoking patients. METHODS: A group of 286 patients
      who underwent arthroscopic suturing of primary rotator cuff injuries between June
      12, 2002, and May 14, 2008, was analyzed. The patients included in the study were
      evaluated using the UCLA scale, with a minimum follow-up of 12 months and average
      of 56.52 months. The variables studied were age, sex, side operated, dominance,
      profile of cigarette use and UCLA index. RESULTS: This study evaluated a total of
      205 patients. Mean age (p = 0.289) and sex (p = 0.124) were analyzed
      statistically between the smoking and non-smoking patients and the two groups
      were considered to be similar. The average UCLA score for the non-smoking
      patients (143) was 34 (32 to 35). The average UCLA score for the smoking patients
      (51) was 33 (29 to 35). There was no statistically significant difference in UCLA
      score (p = 0.123) between the smoking and non-smoking patients. For the purposes
      of statistical analysis, we grouped the small and medium tears (107) and compared
      these with the large and extensive tears (80), between smokers and non-smokers.
      There was no statistically significant difference using the Mann-Whitney test
      regarding the small and medium tears (p = 818). There was a statistically
      significant difference using the Mann-Whitney test regarding the large and
      extended tears, between the smoking and non-smoking patients, such that the non
      smokers showed better UCLA scores (p = 0.038). CONCLUSION: The results from
      arthroscopic suturing of large and extensive rotator cuff injuries are inferior
      among smoking patients.

PMID- 27027007
TI  - EVALUATION OF PRESENTATION OF SIGNS AND SYMPTOMS OF FEMOROACETABULAR IMPINGEMENT
      AFTER EPIPHYSIOLYSIS OF THE PROXIMAL FEMUR.
AB  - The long-bone fractures occur most frequently in the tibial shaft. Adequate
      treatment of such fractures avoids consolidation failure, skewed consolidation
      and reoperation. To classify these fractures, the AO/OTA classification method is
      still used, but it is worthwhile getting to know the Ellis classification method,
      which also includes assessment of soft-tissue injuries. There is often an
      association with compartmental syndrome, and early diagnosis can be achieved
      through evaluating clinical parameters and constant clinical monitoring. Once the
      diagnosis has been made, fasciotomy should be performed. It is always difficult
      to assess consolidation, but the RUST method may help in this. Radiography is
      assessed in two projections, and points are scored for the presence of the
      fracture line and a visible bone callus. Today, the dogma of six hours for
      cleaning the exposed fracture is under discussion. It is considered that an early
      start to intravenous antibiotic therapy and the lesion severity are very
      important. The question of early or late closure of the lesion in an exposed
      fracture has gone through several phases: sometimes early closure has been
      indicated and sometimes late closure. Currently, whenever possible, early closure
      of the lesion is recommended, since this diminishes the risk of infection.
      Milling of the canal when the intramedullary nail is introduced is still a
      controversial subject. Despite strong personal positions in favor of milling,
      studies have shown that there may be some advantage in relation to closed
      fractures, but not in exposed fractures. 

PMID- 27027008
TI  - MINIMALLY INVASIVE ANTEROLATERAL ACCESS ROUTE FOR TOTAL HIP ARTHROPLASTY.
AB  - OBJECTIVE: The aim of this study was to present a minimally invasive
      anterolateral access route and to ascertain whether this enables total hip
      replacement without compromising the quality of the implant positioning, while
      maintaining the integrity of the gluteus muscles. METHOD: A retrospective study
      was conducted on 260 patients (186 females and 74 males) with an average age of
      62 years. There were 18 bilateral cases, totaling 278 hips. All the patients had
      osteoarthritis and had undergone non-cemented total hip arthroplasty (metal-metal
      or metal-polyethylene) between October 2004 and December 2007. A minimally
      invasive anterolateral access route was used, measuring 7 to 10 cm in length,
      according to body weight and the size of the femoral head. The patients were
      assessed clinically regarding age, sex and presence of the Trendelenburg sign,
      and radiologically regarding acetabular and femoral positioning. RESULTS: The
      acetabular inclination was between 30 degrees  and 40 degrees  in 78 patients,
      between 41 degrees  and 50 degrees  in 189 patients, and 51 degrees  or over in
      11 patients. On anteroposterior radiographs to study femoral positioning, the
      positioning was central in 209 cases, 41 presented valgus deviation and 28
      presented varus deviation. On lateral views, 173 were central, 67 anterior and 38
      posterior. The mean duration of the procedure was 63 minutes. Regarding
      complications, there were five cases of infection, three of deep vein thrombosis,
      two of hip dislocation, 80 of lengthening of the lower limbs and five of
      shortening of the operated limb. The Trendelenburg sign was present in four
      cases, of which one showed superior gluteal nerve injury. CONCLUSION: The
      minimally invasive anterolateral access route made it possible to perform total
      hip arthroplasty without compromising the positioning of the implants, thereby
      maintaining the integrity of the gluteus muscles.

PMID- 27027009
TI  - CORRELATION BETWEEN TIME UNTIL SURGICAL TREATMENT AND MORTALITY AMONG ELDERLY
      PATIENTS WITH FRACTURES AT THE PROXIMAL END OF THE FEMUR.
AB  - OBJECTIVE: The primary aim of this study was to analyze the possible association
      between delay in receiving surgical treatment and mortality among elderly
      patients with fractures at the proximal end of the femur. METHODS: 269 patients
      with fractures at the proximal end of the femur (femur neck and intertrochanteric
      fractures) who were treated surgically at Hospital Sao Paulo, UNIFESP, Sao Paulo,
      between January 2003 and December 2007, were studied. The following attributes
      were analyzed and compared with the literature relating to this subject: sex,
      age, type of fracture, classification of the fracture, affected side, synthesis
      used, trauma mechanism, length of hospitalization, waiting time for surgery,
      associated comorbidities, hemogram on admission, type of anesthesia, need for
      blood transfusion, day of the week and season of the year of the fracture.
      RESULTS: The study showed that higher mortality correlated with higher numbers of
      clinical comorbidities, longer hospitalization and use of general anesthesia
      during the surgery. CONCLUSION: There was no association between the time spent
      waiting for surgery and mortality.

PMID- 27027010
TI  - COMPUTATIONAL ANALYSIS BASED ON ARTIFICIAL NEURAL NETWORKS FOR AIDING IN
      DIAGNOSING OSTEOARTHRITIS OF THE LUMBAR SPINE.
AB  - OBJECTIVE: To ascertain the advantages of applying artificial neural networks to
      recognize patterns on lumbar spine radiographies in order to aid in the process
      of diagnosing primary osteoarthritis. METHODS: This was a cross-sectional
      descriptive analytical study with a quantitative approach and an emphasis on
      diagnosis. The training set was composed of images collected between January and
      July 2009 from patients who had undergone lateral-view digital radiographies of
      the lumbar spine, which were provided by a radiology clinic located in the
      municipality of Criciuma (SC). Out of the total of 260 images gathered, those
      with distortions, those presenting pathological conditions that altered the
      architecture of the lumbar spine and those with patterns that were difficult to
      characterize were discarded, resulting in 206 images. The image data base (n =
      206) was then subdivided, resulting in 68 radiographies for the training stage,
      68 images for tests and 70 for validation. A hybrid neural network based on
      Kohonen self-organizing maps and on Multilayer Perceptron networks was used.
      RESULTS: After 90 cycles, the validation was carried out on the best results,
      achieving accuracy of 62.85%, sensitivity of 65.71% and specificity of 60%.
      CONCLUSIONS: Even though the effectiveness shown was moderate, this study is
      still innovative. The values show that the technique used has a promising future,
      pointing towards further studies on image and cycle processing methodology with a
      larger quantity of radiographies.

PMID- 27027011
TI  - PRELIMINARY RESULTS FROM THE METIS-NEWDEAL((r)) TOTAL METATARSOPHALANGEAL
      PROSTHESIS.
AB  - OBJECTIVE: To evaluate the preliminary results from the METIS-Newdeal((r))
      metatarsophalangeal prosthesis for treating hallux rigidus grade III/IV. METHODS:
      This was a prospective study on eight metatarsophalangeal prostheses that were
      placed in six patients between November 2007 and July 2009. The patients' mean
      age was 55 years and the mean follow-up after the surgery was 50 weeks. The
      results were evaluated using the AOFAS-MTP score and x-ray images as controls.
      RESULTS: The AOFAS-MTP score increased significantly from 42p before the surgery
      to 82p after the surgery (? 1.95x), mainly due to improvement in the functional
      level. No intercurrences were identified radiologically. Among the five patients
      who underwent operations, only one expressed dissatisfaction with the surgery:
      this was expressed after early infection appeared at the surgical site, and it
      was the only postoperative complication found. CONCLUSION: Total
      metatarsophalangeal arthroplasty using METIS-Newdeal((r)) presented promising
      short-term results. However, evaluations on a larger number of cases with a
      longer follow-up are needed in order to draw more consistent conclusions.

PMID- 27027012
TI  - GIANT CELL TUMOR IN THE PROXIMAL PHALANX WITH PULMONARY METASTASIS: CASE REPORT
      AND LITERATURE REVIEW.
AB  - This is a case report on a giant cell tumor (GCT) in the proximal phalanx of the
      third finger of the left hand, with pulmonary metastasis. The patient presented
      pain in the finger without any previous history of trauma. Clinical examination,
      radiographic imaging and magnetic resonance imaging were carried out. A
      histological evaluation was carried out from an incisional biopsy, taking the
      hypothesis of GCT. The patient underwent amputation of the finger and the
      diagnosis was confirmed by means of microscopy on the specimen. The patient was
      followed up because of the risk of lung metastasis, which was shown by
      radiographic examination and computed tomography on the chest, and thoracotomy
      was performed. Since then, there has been an improvement in the symptoms that had
      been reported preoperatively, and no local recurrence or new metastasis has been
      found. 

PMID- 27027013
TI  - OCCULT MANUBRIOSTERNAL JOINT INJURY ASSOCIATED WITH FRACTURE OF THE THORACIC
      SPINE.
AB  - The authors report the occurrence of an occult manubriosternal joint injury in
      the initial evaluation on a patient with a thoracic spine fracture (T9). This T9
      fracture was diagnosed in a 37-year-old man and was associated with a partial
      neurological deficit. At the initial evaluation, the radiographs produced did not
      show the manubriosternal joint injury. During rehabilitation, after surgical
      stabilization of the thoracic spine fracture, the patient suddenly felt an
      intense pain accompanied by deformation at the sternal level. From imaging
      examinations, manubriosternal luxation was diagnosed. Because of recurrence of
      the luxation and the incapacitating pain, open reduction and fixation of the
      manubriosternal joint had to be performed. At the 12-month follow-up, the patient
      presented complete recovery of the neurological lesion, consolidation of the
      arthrodesis on the T7-T11 vertebral segment and maintenance of the reduction of
      the manubriosternal joint, which was asymptomatic during daily activities. 

PMID- 27027015
TI  - Charles S. Neer.
AB  - "He has truly made outstanding contributions that have brought clarity out of
      chaos in the variou areas of shoulder surgery. His publications are voluminous,
      and each article is written accurately, clearly and with obvious attention to
      every detail. His versatility as a teacher, researcher, and surgeon is far
      excellence". (Texto do Clinical Orthopaedics and Related Research, 1987). 

PMID- 27027014
TI  - SUBCLAVIAN VEIN THROMBOSIS FOLLOWING FRACTURE OF THE CLAVICLE: CASE REPORT.
AB  - Deep vein thrombosis in the upper limbs is uncommon in the orthopedic literature.
      We report on a case of subclavian vein thrombosis that occurred during
      conservative treatment of a fracture in the middle third of the clavicle. This is
      difficult to diagnose and requires a high degree of suspicion. Treating it may
      prevent fatal thromboembolism. In some rare cases, it has been described in
      association with fractures of the clavicle. 

PMID- 27027016
TI  - TRIBUTE - THE MAN WHO CHANGED THE FACE OF ORTHOPEDICS.

PMID- 27027017
TI  - ORTHOPEDIC SURGERY AMONG THE ELDERLY: CLINICAL CHARACTERISTICS.
AB  - Care for elderly patients undergoing orthopedic surgery, particularly for those
      requiring emergency surgery, needs to take into account an analysis of physical
      capacity and risks specific to elderly individuals, in an attempt to reduce the
      risks. Nevertheless, these remain high in this group. Despite the risks,
      procedures developed promptly have a positive effect on these patients'
      evolution. Coordinated care, composed of teams of specialists within clinical
      medicine, geriatrics, orthopedics, anesthesiology and critical care, along with
      other healthcare professionals, may be highly beneficial for this group of
      patients. 

PMID- 27027018
TI  - ANATOMICAL ACL RECONSTRUCTION WITH DOUBLE BUNDLE: FIRST 40 CASES.
AB  - OBJECTIVE: To discuss the technique of anatomical reconstruction of the anterior
      cruciate ligament (ACL) with a double bundle, the learning curve and the
      preliminary results. METHODS: Forty patients with ACL injury underwent
      reconstruction with an anatomical double bundle, using the semitendinosus tendon
      to remake the anteromedial (AM) band and the gracilis to remake the
      posterolateral (PL) band of the knee. RESULTS: We had two cases of limitation of
      extension, and in one of them, arthroscopic arthrolysis had to be performed; and
      there was one case of deep vein thrombosis. CONCLUSION: ACL reconstruction with
      double bundle proved feasible, despite having a longer learning curve, and the
      advantages of the proposed technique still must be proven compared to the single
      bundle technique.

PMID- 27027019
TI  - RADIOLOGICAL ANALYSIS OF BONE TUNNEL POSITION IN ANTERIOR CRUCIATE LIGAMENT
      RECONSTRUCTION SURGERY: COMPARISON BETWEEN THE OPEN TECHNIQUE AND ARTHROSCOPY VIA
      AN ANTEROMEDIAL PORTAL.
AB  - OBJECTIVES: To evaluate and compare bone tunnel positioning in anterior cruciate
      ligament (ACL) reconstruction surgery using the arthroscopic technique and the
      open technique consisting of arthrotomy. METHOD: A comparative retrospective
      study on 70 patients with ACL lesions was conducted. Thirty-five patients
      underwent ACL reconstruction by means of the open technique and 35 by means of
      the arthroscopic technique using an anteromedial portal. All the patients
      underwent ACL reconstruction using an autologous graft from the middle third of
      the patellar tendon, fixed using interference screws. The postoperative
      radiographs were reviewed and the positioning of the femoral tunnel was evaluated
      using the methods proposed by Harner et al. and Aglietti et al., while the tibial
      tunnel was assessed using the method proposed by Rauschning and Staubli. RESULTS:
      Fifty-four of the patients were male and 16 were female. Their mean age at the
      time of the procedure was 34 years and 3 months, with a range from 17 to 58
      years. The arthroscopic technique was shown to be more accurate than the open
      technique for positioning both the femoral and the tibial bone tunnels.
      CONCLUSIONS: Radiological analysis on the knees subjected to ACL reconstruction
      showed that the positioning of both the femoral and the tibial bone tunnels
      presented less variation when the surgery was performed arthroscopically.

PMID- 27027020
TI  - PREVALENCE OF LESIONS ASSOCIATED WITH TRAUMATIC RECURRENT SHOULDER DISLOCATION.
AB  - OBJECTIVE: To evaluate the prevalence of lesions associated with traumatic
      anterior shoulder instability and the relationships between the prevalence of
      these lesions and the number of episodes and time since symptoms started. METHOD:
      Fifty-seven patients aged 18 to 40 years, with traumatic anterior shoulder
      instability, more than one episode of shoulder dislocation and at least six
      months since the first dislocation, who required surgery to treat the
      instability, were selected. Arthroscopic inspection was performed on all the
      patients to assess any associated lesions. RESULTS: The prevalence of lesions was
      assessed, and Bankart lesions were the most prevalent, followed by Hill-Sachs
      lesions, while rotator cuff injuries were the least prevalent. There was no
      correlation from comparison between the number of episodes of dislocation and the
      prevalence of associated lesions. On the other hand, in relation to the time
      since symptoms started, the patients who had had symptoms for longer times had
      fewer Hill-Sachs lesions. CONCLUSION: It was not possible to affirm that, in
      patients with chronic shoulder instability, the numbers of associated lesions
      increased with the time since symptoms started, or with the number of episodes of
      dislocation.

PMID- 27027021
TI  - MUSCLE INJURIES IN ATHLETES.
AB  - This article had the aim of demonstrating the physiology, diagnosis and treatment
      of muscle injuries, focusing on athletes and their demands and expectations.
      Muscle injuries are among the most common complaints in orthopedic practice,
      occurring both among athletes and among non-athletes. These injuries present a
      challenge for specialists, due to the slow recovery, during which time athletes
      are unable to take part in training and competitions, and due to frequent
      sequelae and recurrences of the injuries. Most muscle injuries (between 10% and
      55% of all injuries) occur during sports activities. The muscles most commonly
      affected are the ischiotibial, quadriceps and gastrocnemius. These muscles go
      across two joints and are more subject to acceleration and deceleration forces.
      The treatment for muscle injuries varies from conservative treatment to surgery.
      New procedures are being used, like the hyperbaric chamber and the use of growth
      factors. However, there is still a high rate of injury recurrence. Muscle injury
      continues to be a topic of much controversy. New treatments are being researched
      and developed, but prevention through muscle strengthening, stretching exercises
      and muscle balance continues to be the best "treatment". 

PMID- 27027022
TI  - ADVANCES IN THE USE OF STEM CELLS IN ORTHOPEDICS.
AB  - Primordial cells or stem cells are multipotent undifferentiated cells with the
      capacity to originate any type of cell in the organism. They may have their
      origins in the blastocyst and thus are classified as embryonic, or tissues
      developed in fetuses, newborns or adults and thus are known as somatic stem
      cells. Bone marrow is one of the main locations for isolating primordial cells,
      and there are two lineages: hematopoietic and mesenchymal progenitor cells. There
      are several uses for these undifferentiated cells in orthopedics, going from
      cartilaginous lesions in osteoarthrosis, osteochondritis dissecans and patellar
      chondromalacia, to bone lesions like in pseudarthrosis or bone losses, or nerve
      lesions like in spinal cord trauma. Studying stem cells is probably the most
      promising field of study of all within medicine, and this is shortly going to
      revolutionize all medical specialties (both clinical and surgical) and thus
      provide solutions for diseases that today are difficult to deal with. 

PMID- 27027023
TI  - FIXATION OF FRACTURES OF THE DISTAL EXTREMITY OF THE RADIUS USING THE MODIFIED
      KAPANDJI TECHNIQUE: EVALUATION OF THE RADIOLOGICAL RESULTS.
AB  - To demonstrate a simple and efficacious option for treating fractures of the
      distal extremity of the radius using Kirschner wires. METHODS: Between September
      2008 and April 2009, 48 patients with fractures of the distal extremity of the
      radius, classified as A3 according to the AO classification, were treated
      surgically using a modification of the Kapandji technique. RESULTS: Out of the 48
      wrists operated, 42 (87.5%) presented postoperative measurements within the
      acceptable limits. We used the parameters of McQuenn and Caspers who considered
      that the radial angulation should be wider than 19 degrees  and the volar
      angulation should be narrower than -12 degrees . All the postoperative volar
      inclination measurements were narrower than -3 degrees . The mean preoperative
      radial inclination was 13.14 degrees  and the mean postoperative value was 21.18
      degrees . The mean preoperative volar inclination was 28.75 degrees  and the mean
      postoperative value was 3.31 degrees . The mean preoperative radial height was
      5.25 mm and the mean postoperative value was 9.48 mm. CONCLUSION: The technique
      described here had excellent stability for treating fractures of the distal
      extremity of the radius classified as A3. It was easy to implement and minimally
      invasive, with minimal surgical complications, and it was inexpensive.

PMID- 27027024
TI  - TERRIBLE TRIAD OF THE ELBOW: EVALUATION OF SURGICAL TREATMENT.
AB  - OBJECTIVES: To evaluate the epidemiology of and surgical results from treating
      elbow fracture-dislocations, including only the cases in which dislocation is
      associated with fracture of the coronoid process and the radial head (terrible
      triad). METHODS: Nineteen patients were evaluated: 12 males and 7 females. The
      medical records were analyzed to gather data about the mechanism of injury,
      fracture pattern, time elapsed until surgery and type of procedure applied. A
      clinical assessment was made to measure elbow range of motion, and the MEPS
      questionnaire was applied. RESULTS: The most common mechanism of injury in our
      sample was a fall from a height (12 patients). All the patients underwent
      surgical treatment and the mean time elapsed between the date of the injury and
      the surgery was 16.1 days. The mean follow-up was 50.3 months. The mean range of
      flexion-extension obtained was 112 degrees  and the mean range of pronation
      supination obtained was 127.9 degrees . The mean score from the MEPS
      questionnaire was 86 points, and excellent and good results were obtained for 15
      patients (79%). The time elapsed until surgery, final flexion-extension range
      greater than 100 degrees  and flexion contracture of less than 30 degrees  were
      shown to have a statistically significant relationship with a good final clinical
      result. Five patients had complications, of which three cases related to
      peripheral nerves, one case to pseudarthrosis and one case to recurrent
      instability. CONCLUSIONS: Despite the severity of the injuries found in the
      terrible triad of the elbow, most of the patients evaluated here achieved elbow
      stability with good clinical results. The factors that led to better clinical
      results were surgery not more than 14 days after the injury, flexion-extension
      range greater than 100 degrees  and flexion contracture less than 30 degrees .

PMID- 27027025
TI  - PROSPECTIVE ASSESSMENT OF THE CLINICAL, RADIOGRAPHIC AND FUNCTIONAL EVOLUTION OF
      TREATMENT FOR UNSTABLE TROCHANTERIC FRACTURES OF THE FEMUR USING A
      CEPHALOMEDULLARY NAIL.
AB  - To assess the clinical, radiological and functional evolution of osteosynthesis
      using a cephalomedullary nail, in unstable trochanteric fractures of the femur,
      over a one-year postoperative follow-up. METHODS: Fourteen men and 23 women of
      mean age 77.7 years were evaluated. Twenty-seven of them had fractures classified
      as AO/ASIF 31A2 and ten as 31A3. The patients were evaluated clinically,
      radiologically and functionally one week, two weeks, one month, two months, six
      months and one year after the operation. RESULTS: The clinical complications
      comprised five cases of death, one case of calcaneal ulcer, one case of acute
      arterial obstruction and two cases of deep vein thrombosis. The radiographic
      evaluation showed that the mean cervicodiaphyseal angle in the immediate
      postoperative period was 132.5 degrees . The mean tip-apex index was 22.8 mm.
      After one year, the mean cervicodiaphyseal angle was 131.7 degrees . Fracture
      consolidation was seen in all the patients six months after the operation, except
      in one case that presented cut-out. There were no cases of fracture below the
      implant. The functional evaluation using the Harris score after one year showed a
      mean of 69.3 points. The evaluation of walking progress showed that after one
      year, 40.6% of the patients had the same ability to walk that they had before the
      fracture. The visual analogue pain scale showed that a significant decrease in
      pain complaints occurred, going from 5.19 in the first week to 2.25 after 1 year.
      CONCLUSION: Osteosynthesis using a cephalomedullary nail resulted in low rates of
      clinical and mechanical complications and adequate functional outcomes.

PMID- 27027026
TI  - TREATMENT OF POST-TRAUMATIC HUMERAL FRACTURES AND COMPLICATIONS USING THE
      OSTEOLINE((r)) EXTERNAL FIXATOR: A TREATMENT OPTION.
AB  - To evaluate the results obtained from treatment of humeral shaft fractures and
      their complications using the Osteoline((r)) uniplanar external fixator. METHODS:
      The radiographic and functional results from 78 patients with humeral shaft
      fractures treated using the uniplanar external fixation technique were
      retrospectively assessed. The patients' ages ranged from 23 to 71 years, with a
      mean of 47 years. Male patients predominated (79%). Out of the 78 patients, 45
      presented open fractures, 14 presented pseudarthrosis and six presented synthesis
      failure. There were no losses during the follow-up and all the patients were
      discharged after fracture consolidation and functional recovery. The results were
      evaluated based on the studies by Catagni, as good, fair or poor. RESULTS:
      Fracture consolidation was observed in 98% of the cases treated with uniplanar
      external fixation. Only one pseudarthrosis case required conversion to rigid
      internal fixation and autologous bone grafting. At the end of the treatment, all
      the patients were discharged with consolidated fractures, without pain, and good
      limb function. CONCLUSION: The external fixation described in this paper was
      shown to be an efficient and safe method for treating humeral shaft fractures and
      their complications. It preserved the local biological status and enabled passive
      and active movement immediately after surgery.

PMID- 27027027
TI  - ARTHROSCOPIC TREATMENT OF ELBOW STIFFNESS.
AB  - To present the arthroscopic surgical technique and the evaluation of the results
      from this technique for treating elbow stiffness. METHODS: Between April 2007 and
      January 2010, ten elbows of ten patients with elbow stiffness underwent
      arthroscopic treatment to release the range of motion. The minimum follow-up was
      11 months, with an average of 27 months. All the patients were male and their
      average age was 32.8 years (ranging from 22 to 48 years). After the arthroscopic
      treatment, they were followed up weekly in the first month and every three months
      thereafter. The clinical evaluation was made using the criteria of the University
      of California at Los Angeles (UCLA). RESULTS: All the patients were satisfied
      with the results from the arthroscopic treatment. The average UCLA score was 33.8
      points. CONCLUSION: Arthroscopic treatment for elbow stiffness is a minimally
      invasive surgical technique that was shown to be efficient for treating this
      complication.

PMID- 27027028
TI  - ARTHROSCOPIC RELEASE OF THE SUPRASCAPULAR NERVE: SURGICAL TECHNIQUE AND
      EVALUATION OF CLINICAL CASES.
AB  - To describe a specific surgical technique for arthroscopic decompression of the
      suprascapular nerve (SSN) and evaluate its preliminary results. METHODS: Ten
      shoulders of nine patients were operated using a technique with portals differing
      from the already-known techniques, which did not use traction and made use of
      materials available within the public healthcare system. RESULTS: Among the ten
      shoulders of nine patients, eight were right shoulders and two were left
      shoulders. The mean age was 69.5 years. The UCLA score increased from 11.7 to
      26.1 points over the postoperative follow-up of 16.6 months. The SF-36
      questionnaire score was 122.9 and the raw pain scale value was 88%. CONCLUSION:
      Arthroscopic decompression of the SSN in accordance with the described technique
      is reproducible and less traumatic than the open techniques. The patients
      achieved improvements in many of the parameters evaluated, particularly with
      regard to pain. Arthroscopic decompression of the SSN may be a therapeutic option
      for pathological compression of the SSN.

PMID- 27027029
TI  - RELATIONSHIP BETWEEN PATELLAR HEIGHT AND RANGE OF MOTION AFTER TOTAL KNEE
      ARTHROPLASTY.
AB  - To evaluate whether, after total knee arthroplasty, there is any correlation
      between patellar height and range of motion (ROM) achieved by patients six months
      after the operation. METHODS: Forty-five patients who underwent total knee
      arthroplasty were assessed at least 12 months after the operation (total of 54
      knees). The maximum and minimum ROM of all the knees was recorded under
      fluoroscopy, along with patellar height according to the Blackburne and Peel
      ratio. Two possible correlations were evaluated: patellar height and ROM; and
      patellar height and ROM variation from before to after the operation. RESULTS: A
      correlation was found between patellar height and postoperative ROM (p = 0.04).
      There was no correlation between patellar height and ROM variation (p = 0.182).
      CONCLUSION: After total knee arthroplasty, the lower the patella is, the worse
      the ROM is.

PMID- 27027030
TI  - HOW CAN BONE TUNNEL ENLARGEMENT IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION
      SURGERY BE MEASURED? DESCRIPTION OF A TECHNIQUE.
AB  - To assess the presence of tibial bone tunnel enlargement after surgery to
      reconstruct the anterior cruciate ligament using quadruple flexor tendon grafts,
      and to propose a new technique for its measurement. METHODS: The study involved
      25 patients aged 18-43 years over a six-month period. The assessment was based on
      radiographs taken immediately postoperatively and in the third and sixth months
      of evolution after operations to reconstruct the anterior cruciate ligament using
      grafts from the tendons of the semitendinosus and gracilis muscles, fixed in the
      femur with a transverse metal screw and in the tibia with an interference screw.
      The radiographs were evaluated in terms of the relative value between the
      diameter of the tunnel and the bone, both at 2 cm below the medial tibial
      condyle. RESULTS: There were significant increases in tunnel diameters: 20.56%
      for radiographs in anteroposterior view and 26.48% in lateral view. Enlargement
      was present in 48% of anteroposterior and lateral radiographs, but was present in
      both views in only 16% of the cases. CONCLUSIONS: Bone tunnel enlargement is a
      phenomenon found in the first months after surgery to reconstruct the anterior
      cruciate ligament. The measurement technique proposed in this study was
      sufficient to detect it.

PMID- 27027031
TI  - FEMORAL ROLL BACK IN TOTAL KNEE ARTHROPLASTY: COMPARISON BETWEEN PROSTHESES THAT
      PRESERVE AND SACRIFICE THE POSTERIOR CRUCIATE LIGAMENT.
AB  - To compare the rollback of the contact point between the femoral component and
      the tibial polyethylene as the knee is flexed, in two types of total knee
      arthroplasty: one that sacrifices and the other that preserves the posterior
      cruciate ligament (PCL). METHODS: Under fluoroscopy, 36 knees from 32 patients
      who underwent total knee arthroplasty were evaluated. Using lateral images, the
      contact points between the femur and the tibial polyethylene with the knee in
      complete extension and at 90 degrees  of flexion were measured, thereby measuring
      the percentage rollback of the femur in arthroplasties in which the PCL was
      sacrificed and in those in which it was preserved. RESULTS: The mean percentage
      rollback of the femur was 13.24% in the cases in which the PCL was sacrificed and
      5.75% in the cases in which it was preserved. The difference between these
      measurements was statistically significant (p = 0.026615). CONCLUSION: In total
      knee arthroplasty, sacrificing the PCL increased the rollback of the contact
      point between the femur and tibia as the knee was flexed up to 90 degrees .

PMID- 27027032
TI  - IS THERE ANY DIFFERENCE IN THE PROGNOSIS FOR PATIENTS WITH PRIMARY OSTEOSARCOMA
      WITH A POOR RESPONSE TO NEOADJUVANT CHEMOTHERAPY BETWEEN HUVOS GRADES I AND II?
AB  - Would there be any difference in the prognosis for patients who presented, for
      example, 8% or 88% tumor necrosis induced by chemotherapy, even though both
      individuals were considered to be poor responders? The aim of this study was to
      compare the prognoses for different histological grades (Huvos grade I versus
      grade II), consequent to chemotherapy, among patients with primary osteosarcoma
      that was not metastatic at diagnosis. METHODS: Twenty-four patients admitted to a
      referral center between 2000 and 2004 were selected for the study. The
      accumulated chances of survival were calculated using the Kaplan-Meier technique.
      Huvos grades I and II for necrosis consequent to chemotherapy were evaluated as
      variables in order to determine their prognostic value, in relation to local
      recurrence-free survival, metastasis-free survival and overall survival, using
      the log-rank test. RESULTS: Comparing Huvos grades I and II, the following P
      values for survival were attained: local recurrence-free survival (P = 0.731),
      metastasis-free survival (P = 0.596) and overall survival (P = 0.669).
      CONCLUSION: In this series, Huvos grades I and II did not have any comparative
      prognostic value and had similar behavior.

PMID- 27027033
TI  - STUDY ON THE APPLICABILITY OF THE MODIFIED TOKUHASHI SCORE IN PATIENTS WITH
      SURGICALLY TREATED VERTEBRAL METASTASIS.
AB  - To present the results obtained from surgical treatment of patients with
      vertebral metastases, comparing them with the modified Tokuhashi score in order
      to validate the applicability of this score for prognostic predictions and for
      choosing surgical treatments. METHODS: This was a retrospective study on 157
      patients treated surgically for spinal metastasis in Erastus Gaertner Hospital in
      Curitiba. The Tokuhashi score was applied retrospectively to all the patients.
      The patients' actual survival time was compared with the expected survival time
      using the Tokuhashi score. RESULTS: There were 82 females and 75 males. The most
      frequent location of the primary tumor was the breast. The thoracic region was
      involved in 66.2%, lumbar region in 65.6%, cervical region in 15.9% and sacral
      region in 12.7%. All the patients underwent surgical treatment. The most frequent
      indication for treatment was intractable pain (89.2%). There was partial or
      complete improvement in a majority of the cases (52.2%). Out of 157 cases
      studied, 86.6% died. The maximum survival time was 13.6 years, the minimum was 3
      days and the mean was 13.2 months. The following frequencies of Tokuhashi scores
      were found among the operated cases: up to 8 points, 111 cases; 9-11 points, 43
      cases; and 12-15 points, three cases. The mean survival time in months for all
      157 patients according to the Tokuhashi score was: 0-8 points, 15.4 months; 9-11
      points, 11.4 months; and 12-15 points, 12 months. CONCLUSION: Unlike the
      nonsurgical approach recommended by Tokuhashi for patients with lower scores,
      this group in our study was sent for surgery, with better results than those of
      non-operated patients reported by Tokuhashi.

PMID- 27027034
TI  - EVALUATION OF METATARSAL RELATIONSHIPS IN THE BIOMECHANICS OF 332 NORMAL FEET
      USING THE METHOD OF MEASURING RELATIVE LENGTHS.
AB  - To identify the mean normal length of the metatarsals and the most common
      metatarsal formulas through a simple measurement method, thereby providing
      surgeons with data for planning treatment on symptomatic individuals with
      biometric abnormalities of the foot. METHODS: We evaluated and measured
      dorsoplantar weight-bearing radiographs of normal adult feet (83 males and 83
      females). RESULTS: We found relative mean lengths for metatarsus I of 125.4 mm
      for males and 115.1 mm for females; for metatarsus II, 127.8 mm for males and
      117.3 mm for females; for metatarsus III, 123.4 mm for males and 113.5 mm for
      females; for metatarsus IV, 114.2 mm for males and 105.3 mm for females; for
      metatarsus V, 99.5 mm for males and 91.7 mm for females. The mean forefoot width
      was 87.1 mm for males and 80.8 mm for females. CONCLUSION: Feet with index minus
      occurred most frequently in both sexes, although all three metatarsal formulas
      can be considered to be normal patterns. The mean normal pattern for males and
      females respectively was the following: metatarsus I 2.4 mm and 2.2 mm shorter
      than metatarsus II; metatarsus III 4.4 mm and 3.8 mm shorter than metatarsus II;
      metatarsus IV 9.2 mm and 8.2 mm shorter than metatarsus III; metatarsus V 14.7 mm
      and 13.6 mm shorter than metatarsus IV.

PMID- 27027035
TI  - MAGNETIC RESONANCE IMAGING FOR DIAGNOSING THE PRE-SLIP STAGE OF THE CONTRALATERAL
      PROXIMAL FEMORAL EPIPHYSIS IN PATIENTS WITH UNILATERAL EPIPHYSIOLYSIS.
AB  - To assess the importance of using conventional magnetic resonance imaging and T2
      mapping to determine the pre-slip stage of the contralateral epiphysis in
      patients with a clinical and radiographic diagnosis of unilateral proximal
      femoral epiphysiolysis who were initially treated with in-situ fixation. METHODS:
      This prospective clinical study on 11 patients with unilateral epiphysiolysis was
      conducted between February 2009 and August 2010, using magnetic resonance imaging
      on the contralateral hip. RESULTS: We observed abnormalities in the proximal
      femoral capital physis of the contralateral unaffected hip, with edema under the
      growth plate in 27% of the patients assessed. CONCLUSION: Magnetic resonance
      imaging is an early and sensitive method for detecting the pre-slip stage of the
      proximal femoral epiphysis.

PMID- 27027036
TI  - PHYSICOCHEMICAL CHARACTERIZATION OF LYOPHILIZED BOVINE BONE GRAFTS.
AB  - To evaluate the physicochemical characteristics of lyophilized bovine grafts
      manufactured on a semi-industrial scale (Orthogen; Baumer S/A*) in accordance
      with a protocol previously developed by the authors. METHODS: The lyophilized
      bovine bone grafts were characterized by means of scanning electron microscopy
      (SEM), energy dispersive spectroscopy (EDS), X-ray diffractometry (XRD),
      thermogravimetric (TG) analysis, differential exploratory scanning calorimetry
      (DSC) and Fourier-transform infrared (FT-IR) spectroscopy. RESULTS: Ca was the
      main component (60%) found in the samples, followed by P (28%) and O (5%). The
      mean (sd) pore size was 316 MUm (146.7), ranging from 91.2 to 497.8 MUm, and
      333.5 MUm (304.8), ranging from 87.2 to 963.9 MUm, at 50x and 150x magnification,
      respectively. The hydroxyapatite peaks were at 26 degrees C and 32 degrees C, and
      mass losses were observed between 250 degrees C and 640 degrees C, corresponding
      to organic material and water. Two temperature transitions (45.67 degrees C and
      91.89 degrees C) showed denaturation of type 1 collagen and dehydration of
      hydroxyapatite. CONCLUSION: The physicochemical assessment of lyophilized bovine
      bone grafts in accordance with the protocol developed at semi-industrial scale
      confirmed that this product presents excellent biocompatibility, with
      characteristics similar to natural bone.

PMID- 27027037
TI  - RANDOMIZED CONTROLLED CLINICAL TRIALS IN ORTHOPEDICS: DIFFICULTIES AND
      LIMITATIONS.
AB  - Randomized controlled clinical trials (RCTs) are considered to be the gold
      standard for evidence-based medicine nowadays, and are important for directing
      medical practice through consistent scientific observations. Steps such as
      patient selection, randomization and blinding are fundamental for conducting a
      RCT, but some additional difficulties are presented in trials that involve
      surgical procedures, as is common in orthopedics. The aim of this article was to
      highlight and discuss some difficulties and possible limitations on RCTs within
      the field of surgery. 

PMID- 27027039
TI  - PUBIS STRESS FRACTURE IN A 15-YEAR-OLD SOCCER PLAYER.
AB  - This case report presents a 15-year-old football player who was diagnosed with a
      pubis stress fracture and underwent conservative treatment with satisfactory
      results. After a review of the literature, the clinical picture, diagnosis and
      treatment are described. The importance of this paper comes from the rarity of
      finding reports about this kind of injury in the literature. 

PMID- 27027038
TI  - TOTAL KNEE ARTHROPLASTY IN A PATIENT WITH HOFFA FRACTURE PSEUDARTHROSIS: CASE
      REPORT.
AB  - A rare occurrence of a case of Hoffa fracture pseudarthrosis in an alcoholic
      patient with genu valgum associated with venous insufficiency who underwent total
      knee arthroplasty is reported. The literature is reviewed and the main factors
      for surgical indication of total knee arthroplasty after a fracture of the knee
      are discussed. Total knee arthroplasty was a viable option in a 60-year-old
      patient with Hoffa fracture pseudarthrosis and comorbidities. 

PMID- 27027041
TI  - MATTERS OF LIFE FOR A MATURE ORTHOPEDIST.

PMID- 27027040
TI  - LOCALIZED PIGMENTED VILLONODULAR SYNOVITIS: CASE REPORT.
AB  - This case concerned a female patient with a complaint of pain in the anterior
      region of her left knee during and after sports activities, followed by joint
      blockage three months ago. From imaging examinations, simple radiography of the
      knee was normal and magnetic resonance showed a solid expansive mass, possibly
      corresponding to soft-tissue chondroma or focal nodular synovitis. Arthroscopic
      resection of the lesion was performed, and the diagnosis of diffuse giant cell
      tumor resembling localized pigmented villonodular synovitis (PVNS) was made from
      the result of the anatomopathological examination. The patient presented good
      clinical evolution, with disappearance of symptoms and return to physical
      activities. 

PMID- 27027042
TI  - EDITING THE RBO.

PMID- 27027043
TI  - UPDATING OF THE ANATOMY OF THE EXTENSOR MECHANISM OF THE KNEE USING A THREE
      DIMENSIONAL VIEWING TECHNIQUE.
AB  - The knee extensor mechanism is a complex structure formed by the quadriceps
      muscle and tendon, the patella, the patellar tendon and the ligaments that
      surround and help stabilize the knee. Through using a three-dimensional viewing
      technique on images of the knee extensor apparatus, we aimed to didactically show
      the structures that compose this bone-muscle-ligament complex. Anatomical
      dissection of the knee with emphasis on the structures of its extensor mechanism
      was performed, followed by taking photographs using a camera and lenses suitable
      for simulating human vision, through a technique for constructing three
      dimensional images. Then, with the aid of appropriate software, pairs of images
      of the same structure from different angles simulating human vision were overlain
      with the addition of polarizing layer, thereby completing the construction of an
      anaglyphic image. The main structures of the knee extensor mechanism could be
      observed with a three-dimensional effect. Among the main benefits relating to
      this technique, we can highlight that in addition to teaching and studying
      musculoskeletal anatomy, it has potential use in training for surgical procedures
      and production of images for diagnostic tests. 

PMID- 27027044
TI  - BISPHOSPHONATE-INDUCED MAXILLOFACIAL OSTEONECROSIS IN OSTEOPOROTIC INDIVIDUALS.
AB  - Bisphosphonate-related osteonecrosis of the maxillae may be an important
      complication of long-term osteoporosis treatment. The possibility of
      osteonecrosis of the maxillae in patients exposed to nitrogenated bisphosphonates
      was first described in 2003. Since then, case reports and retrospective studies
      have demonstrated higher percentages of occurrence of osteonecrosis in patients
      who have used or are using bisphosphonates. Although this complication may be
      spontaneous, invasive oral procedures have a role as risk factors associated with
      dental procedures such as tooth extractions and other bone operations. In
      addition, tooth infections and periodontal disease have been reported to be the
      main risk factors for development of bisphosphonate-induced osteonecrosis of the
      maxillae. For this reason, dentists, general clinicians, orthopedists,
      geriatricians and oral-maxillofacial surgeons need to be aware of this problem
      and work in a multidisciplinary environment, thereby stimulating early diagnosis
      and prevention of further potential cases. 

PMID- 27027045
TI  - FLOATING ELBOW IN CHILDREN: A DESCRIPTIVE STUDY OF 31 CASES ATTENDED IN A
      REFERENCE CENTER FOR PEDIATRIC TRAUMA.
AB  - OBJECTIVE: To conduct a descriptive analysis on 31 cases of children with
      floating elbow who were attended at our clinic between 1994 and 2009, and to
      review the literature relating to this topic. METHODS: Data were obtained through
      examining the medical records. The following variables were used: age, gender,
      side, mechanism, type of fracture, classification, treatment and complications.
      RESULTS: Twenty-four patients (77.4%) were male and seven (22.6%) were female.
      The mean age was 8.5 (+/- 3.2) years, ranging from one to 14 years. The left side
      was predominantly affected (67.7%). The commonest injury mechanism was a fall
      from a height (74.2%). All the supracondylar fractures were Gartland type III.
      Distal radius fractures alone, of Salter-Harris type II, were diagnosed in 22
      patients (71%). Open fractures occurred in 22 cases (71%). Closed reduction and
      application of a plaster cast for a closed fracture of the distal radius was
      performed in two patients (6.45%). Simultaneous conservative treatment for two
      fractures was not used. Sixteen supracondylar fractures (54.8%) were fixed using
      crossed wires, at 90 degrees  to each other, and in 14 cases (45.16%), an
      intramedullary wire was used together with another wire introduced through the
      lateral epicondyle at 45 degrees . The following complications were observed:
      deformed consolidation (10%), nerve injuries (6%), compartment syndrome (3%) and
      pin path infection (16%). CONCLUSIONS: This is an uncommon injury that in most
      cases results from high-energy trauma. Surgical treatment for both fractures is
      recommended by most authors. Ulnar nerve injuries were correlated with the
      fixation method, but no neurological injuries were triggered by the initial
      trauma.

PMID- 27027046
TI  - SURGICAL TREATMENT OF DISTAL RADIUS FRACTURES WITH A VOLAR LOCKED PLATE:
      CORRELATION OF CLINICAL AND RADIOGRAPHIC RESULTS.
AB  - OBJECTIVES: To analyze and correlate the clinical and radiographic results from
      patients with distal radius fractures who underwent surgical treatment with a
      fixed-angle volar locked plate. METHODS: Sixty-four patients with distal radius
      fractures were evaluated. They all underwent surgical treatment with a volar
      locked plate for the distal radius, with a minimum of six months of postoperative
      follow-up. They underwent a physical examination that measured range of motion
      and grip strength, answered the Disabilities of the Arm, Shoulder, and Hand
      (DASH) questionnaire and underwent radiographic examination. RESULTS: In the
      physical examination on the patients, all the range-of-motion measurements were
      reduced. Grip strength measured in kgf was on average 85.8% of the strength on
      the unaffected side. The mean DASH score was 15.99. A significant relationship
      was found between lower DASH scores and losses of extension and grip strength. On
      the radiographs, the mean values in relation to the unfractured side were 84.0%
      for radial inclination, 85.4% for radial length and 86.8% for volar deviation of
      the radius. Loss of radial length was correlated with losses of extension and
      grip strength.

PMID- 27027047
TI  - CROSS-SECTIONAL STUDY ON DIFFERENT ENTRY POINTS FOR ANTEROGRADE FEMORAL
      INTRAMEDULLARY OSTEOSYNTHESIS.
AB  - OBJECTIVE: To analyze the degree of knowledge among professionals who treat
      fractures using the recommended technique, with regard to correlating the nail
      with the entry point that is considered appropriate. METHODS: A questionnaire
      that presented five types of nail and simulated a transverse diaphyseal fracture
      of the femur was developed. RESULTS: Responses regarding the entry points
      corresponding to choosing the type of nail were obtained from 370 orthopedists
      who were participating in the 41(st) Brazilian Congress of Orthopedics and
      Traumatology. It was observed that only 20% correctly identified the entry point
      and that there was no difference between the professionals within the specialty
      of Traumatology and the others. CONCLUSION: It was concluded that the majority of
      the physicians attending the congress were unaware of the entry points.

PMID- 27027048
TI  - PROSPECTIVE STUDY ON SEVENTY-SIX CASES OF FRACTURED ACETABULUM WITH SURGICAL
      TREATMENT.
AB  - OBJECTIVE: To conduct a prospective study on unstable and incongruent fractures
      of the acetabulum, in comparison with the literature, covering the type of
      access, fixation materials, degree of reduction, type of fracture and results
      after surgery. METHODS: The authors evaluated 76 patients with unstable and
      incongruent fracture of the acetabulum between January 1999 and December 2009.
      The Marvin Tile classification was used, and all cases were treated surgically
      using the technique recommended by the AO-ASIF group. RESULTS: The radiological
      evaluation was done in accordance with the Ruesch criteria, and good, excellent
      or perfect results were obtained for 64 patients (84.2%). The clinical evaluation
      was done in accordance with the Harris criteria, and good or excellent results
      were obtained for 62 patients (81.6%). The complications were assessed and, in
      comparison with the literature, were shown to be compatible with previous reports
      even after the statistical analysis. CONCLUSION: It was concluded that anatomical
      reduction and stable fixation are important for good results.

PMID- 27027049
TI  - SHORT-TERM EFFICACY OF LOW-LEVEL LASER THERAPY IN PATIENTS WITH KNEE
      OSTEOARTHRITIS: A RANDOMIZED PLACEBO-CONTROLLED, DOUBLE-BLIND CLINICAL TRIAL.
AB  - OBJECTIVE: This study was designed to evaluate the short-term efficacy of low
      level laser therapy (LLLT) for improving pain and function in patients with knee
      osteoarthritis. METHODS: Forty-seven patients with knee osteoarthritis (79
      knees), of both genders, participated in this randomized controlled double-blind
      clinical trial. They were randomly allocated to two groups: laser group with 25
      patients (41 knees) and placebo group with 22 patients (38 knees). LLLT was
      performed three times a week, totaling nine sessions, using a AsGa 904 nm laser
      with mean power of 60 mW and beam area of 0.5 cm(2). Nine points were irradiated
      on the knee, with energy of 3.0 J/point. The placebo group was treated with the
      same laser device, but with a sealed probe. Evaluations using Lequesne, visual
      numerical scale (VNS), Timed Up and Go (TUG), goniometry and dynamometry were
      conducted before the treatment started and after the nine sessions of LLLT.
      RESULTS: A significant improvement in pain and function was found in all the
      assessments applied to the laser group. On comparing the laser group with the
      placebo group, significant differences were found in the VNS-resting and Lequesne
      evaluations. CONCLUSION: Treatment with LLLT improves pain and function over the
      short term in patients with knee osteoarthritis.

PMID- 27027050
TI  - MICROSURGICAL TRANSFER OF THE GRACILIS MUSCLE FOR ELBOW FLEXION IN BRACHIAL
      PLEXUS INJURY IN ADULTS: RETROSPECTIVE STUDY OF EIGHT CASES.
AB  - OBJECTIVE: Treating brachial plexus injuries is a major challenge, especially
      lesions that are presented late, with more than 12 months of evolution. We
      retrospectively analyzed patients who underwent one of the possibilities for
      attempting to restore the function of upper limbs affected under such conditions:
      microsurgical transfer of the gracilis muscle for elbow flexion. METHODS: Eight
      patients were included, divided into two groups: one in which the procedure
      consisted of neurorrhaphy of the muscle flap with sural nerve grafting and
      anastomosis more distally; and the other, in which the neurorrhaphy was performed
      directly on the spinal accessory nerve, with anastomosis in thoracoacromial
      vessels. RESULTS: We found a significant difference between the groups. A greater
      number of satisfactory results (75% M4) were found among patients who underwent
      direct neurorrhaphy, whereas the procedure using grafts for neurorrhaphy was less
      successful (25% M4). CONCLUSION: Patients who underwent microsurgical functional
      transfer of the gracilis muscle in which vascular anastomoses were performed in
      thoracoacromial vessels presented better functional outcomes than shown by those
      whose anastomoses were in the brachial artery with subsequent use of a nerve
      graft.

PMID- 27027051
TI  - MEDIUM-TERM ASSESSMENT OF TOTAL KNEE ARTHROPLASTY WITH IMPLANT MADE IN BRAZIL.
AB  - OBJECTIVE: This study assessed 47 patients who underwent total knee arthroplasty
      (TKA) with implants manufactured in Brazil, with a mean follow-up of five years.
      METHODS: This was a retrospective study at Santa Casa de Misericordia Hospital in
      Rio de Janeiro, from January 1993 to December 2002. The sample comprised 47
      patients (44 females and three males) who underwent TKA, totaling 58 knees. The
      patients' ages ranged from 46 to 83 years. A diagnosis of osteoarthritis or
      rheumatic disease was confirmed in all the patients. RESULTS: In this
      investigation, all the patients underwent cemented TKA with preservation of the
      posterior cruciate ligament. The length of follow-up ranged from 5 to 17 years.
      The functional assessment criterion used was the one of the Hospital for Special
      Surgery (HSS), and this yielded an average of 87 points after the operation. The
      radiographic criterion used was the Knee Society Total Knee Arthroplasty
      Roentgenographic Evaluation and Scoring System. We had three cases with a
      radiolucent line without implant loosening, which were asymptomatic from a
      clinical standpoint. CONCLUSION: The total knee arthroplasty procedures using an
      implant made in Brazil were performed by a trained and experienced team. To date,
      over the clinical follow-up on these patients with knee osteoarthritis or
      rheumatoid arthritis, the results have been seen to be satisfactory.

PMID- 27027052
TI  - PROSPECTIVE AND COMPARATIVE STUDY ON FUNCTIONAL OUTCOMES AFTER OPEN AND
      ARTHROSCOPIC REPAIR OF ROTATOR CUFF TEARS.
AB  - OBJECTIVE: To prospectively assess the surgical results from patients undergoing
      repairs to rotator cuff injuries via open and arthroscopic procedures, with
      regard to functional and clinical features, and by means of ultrasound
      examinations, and to compare occurrences of renewed tearing. METHODS: Sixty
      patients underwent operations performed by the same surgeon (29 via open surgery
      and 31 via arthroscopy), to repair complete rotator cuff tears. The procedures
      were performed at Hospital Governor Israel Pinheiro (HGIP) and Mater Dei Hospital
      in Belo Horizonte, Minas Gerais, between August 2007 and February 2009. The
      patients were assessed functionally by means of the UCLA score before and after
      the operation, and magnetic resonance imaging was done before the operation. All
      the patients were reassessed at least 12 months after the operation, and an
      ultrasound examination was also performed at this time. RESULTS: Out of the 29
      patients who underwent open surgery, 27 (93.1%) presented good or excellent
      results, with a mean UCLA score of 32 after the operation. Their mean follow-up
      was 14 months. Three patients presented renewed tearing on ultrasound, of whom
      one remained asymptomatic. Out of the 31 patients who underwent arthroscopic
      procedures, 29 (93.5%) presented good or excellent results, with a mean UCLA
      score of 33 after the operation. Their mean follow-up was 19 months. Two patients
      presented renewed tearing, of whom one remained asymptomatic and one evolved with
      loosening of an anchor, with an unsatisfactory result. CONCLUSION: The repairs on
      rotator cuff injuries presented good results by means of both open surgery and
      arthroscopy, with similar functional results in the two groups and similar rates
      of renewed tearing.

PMID- 27027053
TI  - RESULTS FROM LATARJET SURGERY FOR TREATING TRAUMATIC ANTERIOR SHOULDER
      INSTABILITY ASSOCIATED WITH BONE EROSION IN THE GLENOID CAVITY, AFTER MINIMUM
      FOLLOW-UP OF ONE YEAR.
AB  - OBJECTIVE: Evaluate the results from the Latarjet procedure in patients with
      anterior recurrent dislocation of the shoulder who present bone loss of the
      glenoid cavity greater than 25%. METHODS: Twenty six male patients underwent the
      Latarjet procedure, The bone loss was evaluated by means of radiography using the
      Bernageau view and by means of CAT scan. The patients were evaluated with regard
      to range of motion, using the Rowe and UCLA scales, before and after the
      operation, and by radiographs to assess the presence of arthrosis, position and
      consolidation of the graft and positioning of the screws. Statistical analysis
      was used to assess whether there was any relationship between the number of
      episodes of dislocation and the presence of arthrosis, , and any relationship
      between arthrosis and limitations on lateral rotation. Differences in range of
      motion between the operated and unaffected sides and in the UCLA and Rowe scale.
      RESULTS: The means for elevation and lateral rotation were statistically poorer
      on the operated side. The UCLA and Rowe scale showed that there was a
      statistically significant improvement in the clinical-functional results (P <
      0.001 for both). There was a relationship between the number of episodes of
      dislocation and the presence of arthrosis, We also did not observe any
      correlation between limitations on lateral rotation and arthrosis. CONCLUSION:
      The Latarjet procedure is an efficient method for cases of severe erosion of the
      glenoid margin.

PMID- 27027054
TI  - RESULTS FROM CLINICAL AND RADIOLOGICAL FOLLOW-UP, AFTER SURGICAL TREATMENT OF
      CHONDROBLASTOMA.
AB  - OBJECTIVES: To evaluate the long-term clinical and radiological results from
      patients who underwent surgical treatment of chondroblastoma, between 2003 and
      2009, by the same surgical team, using the same operative technique. METHODS: A
      retrospective study was conducted on 12 patients with histological diagnoses of
      chondroblastoma, who were attended between 2003 and 2009 at the Pius XII
      Foundation (Barretos Cancer Hospital, Barretos, State of Sao Paulo). These
      patients underwent surgical treatment with intralesional resection of the tumor,
      adjuvant electrocauterization and replacement with methyl methacrylate (11 cases)
      or an autologous graft from the iliac crest (one case). The preoperative
      evaluation included physical examination, plain radiographs of the site, magnetic
      resonance imaging, computed axial tomography and bone scintigraphy. The patients
      were assessed clinically and radiologically according to a predefined protocol,
      with a series of plain radiographs, and a functional assessment in accordance
      with the Enneking functional score. RESULTS: The average age at the time of
      diagnosis was 14 years and 4 months. The most frequent location affected was the
      distal femoral epiphysis (75%), followed by the proximal tibial epiphysis (16.6%)
      and the calcaneus (8.4%). There was higher prevalence among the female patients
      than among the male patients (3:1). In three cases, preoperative biopsy was
      necessary. During the follow-up, there was no evidence of local tumor recurrence,
      and all the patients presented an excellent functional result from the surgical
      technique used, with Enneking scores ranging from 20 to 30. CONCLUSION: Surgical
      treatment of chondroblastoma, using intralesional resection, adjuvant
      electrocauterization and replacement with methyl methacrylate or bone graft
      produced good results.

PMID- 27027055
TI  - RESULTS FROM BI-CONTACT((r)) TOTAL ELBOW ARTHROPLASTY: MULTICENTER STUDY.
AB  - OBJECTIVE: To describe the initial experience of four orthopedic clinics from
      using Bi-Contact((r)) total elbow arthroplasty (TEA), reporting the results and
      complications of the procedure. METHODS: This was a retrospective study, through
      analysis on the medical records of patients who underwent primary TEA using a
      prosthesis model developed in conjunction with IOT-HCFMUSP. Forty-six elbows (45
      patients) that were operated at four orthopedic clinics between 2000 and 2009
      were evaluated. RESULTS: The majority of the patients were female (74%), and the
      median age was 62.5 years. The diagnoses encountered were trauma sequelae
      (47.83%), rheumatoid arthritis (32.61%), primary osteoarthrosis (8.7%), acute
      fractures (6.52%) and heterotopic ossification (2.17%). The median length of
      follow-up was 2.08 years (0.25-9). The procedure significantly alleviated pain
      and improved range of motion. It was observed that at least one complication was
      present in 69.57% of the cases, and the main ones were infection (28.26%), need
      for revision (28.26%), intraoperative fracture (15.22%) and aseptic loosening
      (15.22%). CONCLUSION: Bi-Contact((r)) TEA provided significant alleviation of
      pain and improvement of range of motion in the present series. The complication
      rate was high, and the most frequently observed complications were infection,
      aseptic loosening and intraoperative fracture.

PMID- 27027056
TI  - BENDING RADIOGRAPHS AS A PREDICTIVE FACTOR IN SURGICAL CORRECTION OF ADOLESCENT
      IDIOPATHIC SCOLIOSIS.
AB  - OBJECTIVE: To evaluate the use of x-rays in dorsal decubitus, as a predictive
      factor for surgical correction of the main thoracic curve using pedicle screws,
      on patients with idiopathic adolescent scoliosis. METHOD: Twenty patients with
      idiopathic adolescent scoliosis of Lenke types 1A and 1B who were operated using
      a technique only involving pedicle screws by means of the posterior route were
      evaluated clinically and radiographically. The curve flexibility was calculated
      by means of active supine lateral oblique radiographs. The postoperative values
      for the main thoracic curve were included in a mathematical equation proposed by
      Cheung et al., with the aim of predicting the expected angular result from the
      surgical correction. The difference between the expected and actual postoperative
      results was then investigated regarding its statistical significance. RESULTS:
      There was statistical significance for all the cases studied, between the values
      predicted before the operation and the radiographic findings immediately after
      the operation (p < 0.005). CONCLUSIONS: It is possible to predict the percentage
      surgical correction of the main thoracic curve that will be achieved using
      pedicle screws in patients with idiopathic adolescent scoliosis of Lenke types 1A
      and 1B, by means of preoperative supine oblique radiographs.

PMID- 27027058
TI  - TIBIAL COMPONENT IN REVISION OF TOTAL KNEE ARTHROPLASTY: COMPARISON BETWEEN
      CEMENTED AND HYBRID FIXATION.
AB  - OBJECTIVE: To compare the clinical, radiographic and medium-term follow-up
      results from two fixation methods for the tibial component in revision procedures
      on total knee prostheses: cemented (tray and stem) and hybrid (cemented tray and
      uncemented, nonporous canal-filling stem). METHODS: Between August 1999 and
      November 2005, 30 revision procedures on total knee arthroplasties were performed
      on 26 patients, who were divided between group I (cemented fixation; 21 knees)
      and group II (hybrid fixation; nine knees). The mean follow-up was 52 months and
      no patients were lost from the follow up. RESULTS: No differences in the scores
      from the WOMAC and Knee Society questionnaires were observed between the two
      groups. One patient in group I presented radiographic signs of loosening. Two
      patients (one in each group) complained of pain in the diaphyseal region,
      compatible with the location of the stem tip. The pedestal radiographic sign was
      observed in 89% of the knees with uncemented stems and in none of the cemented
      group. CONCLUSION: The comparative analysis between the two methods did not show
      any differences regarding clinical and radiographic parameters, or arthroplasty
      survival.

PMID- 27027057
TI  - COMPARATIVE MACROSCOPIC STUDY OF OSTEOCHONDRAL DEFECTS PRODUCED IN FEMURS OF
      RABBITS REPAIRED WITH BIOPOLYMER GEL CANE SUGAR.
AB  - OBJECTIVE: To study the surface, coloring, consistency, continuity and healing of
      osteochondral defects produced in the femoral condyles of rabbits and filled with
      sugar cane biopolymer gel (SCBG), after 90, 120 and 180 days, and in comparison
      with a control group. METHOD: Sixteen adult New Zealand white rabbits aged 6 to 7
      months, weighing between 2 and 2.5 kg and without locomotor system abnormalities
      were studied. In all the animals, a defect was made in the femoral condyles of
      the right and left knees, measuring 3.2 mm in diameter and 4 mm in depth, using a
      trephine. The animals were divided into two groups: study group formed by the
      right knees, in which the medial and lateral condyles received implants of SCBG;
      and control group formed by the left knees, in which the medial and lateral
      condyles were allowed to heal naturally. The knees were assessed 90, 120 and 180
      days after the operation. After the animals had been sacrificed, the anatomical
      specimens were resected and placed in Bouin's solution. They were then
      photographed with a Nikon Coolpix 5400((r)) coupled to a Nikon SM2800((r))
      stereoscopic loupe, to analyze the surface, coloring, consistency, continuity and
      healing. RESULTS: The results were evaluated using the chi-square test. There
      were no significant differences in the macroscopic assessments of healing between
      the study and control groups. CONCLUSION: With regard to the surface, coloring,
      consistency, continuity and healing of the defects, the macroscopic appearance of
      the tissue repaired with SCBG was similar to that of the control group.

PMID- 27027059
TI  - FEMORAL INSERTION OF THE POSTERIOR CRUCIATE LIGAMENT: AN ANATOMICAL STUDY.
AB  - OBJECTIVE: To identify objective parameters to guide correct location of the
      posterior cruciate ligament (PCL) in the femur. METHODS: The PCLs of 20 human
      cadavers were resected. The following portions were measured: distance from the
      most distal portion of the PCL, close to the roof, to the most anterior edge of
      the cartilage (AB); distance from the most proximal portion of the PCL, close to
      the roof, to the most anterior cartilage (AC); distance between the two parts of
      the ligament close to the roof (BC); distance from the distal edge in its
      posterior portion, to the more posterior joint edge (DE); distance from the
      distal edge of the ligament in its posterior portion, to the intercondylar roof
      (DF); and finally, the format of the ligament insertion and area of coverage on
      the femoral condyle. RESULTS: The PCL has the shape of a quarter ellipse, with an
      average area of 153.5mm(2). The mean distances found were: AB of 2.1mm, AC of
      10.7mm, BC of 8.6mm DE of 12.4mm and DF of 16.8mm. CONCLUSIONS: The edge close to
      the roof of the anterolateral bundle is closer to the joint cartilage (2.1mm)
      than the posteromedial bundle is, which is 12.4mm from the edge proximal to the
      cartilage. These references should assist in better and more accurate positioning
      of femoral tunnels in PCL reconstruction.

PMID- 27027060
TI  - EXTRA-ARTICULAR FRACTURE OF THE MEDIAL END OF THE CLAVICLE ASSOCIATED WITH TYPE
      IV ACROMIOCLAVICULAR DISLOCATION: CAAE REPORT.
AB  - Fractures of the clavicle and acromioclavicular dislocations are very common
      injuries when they occur separately. The combination of an acromioclavicular
      dislocation and a fracture of the lateral third of the clavicle is not rare.
      However, there are very few reported cases of acromioclavicular dislocations
      associated with fractures of the middle third of the clavicle; those associated
      with fractures of the medial third are even rarer. We report the case of an adult
      male who suffered an acromioclavicular dislocation (type IV) associated with a
      displaced extra-articular fracture of the medial end of the clavicle (Almann
      group 3) in a cycling accident. The patient was treated during the acute phase
      with open reduction and internal fixation of the two lesions. At the clinical
      evaluation 12 months after the surgery, the patient was asymptomatic, with full
      active and passive mobility, and normal strength and endurance of the shoulder
      girdle. Radiographs and a three-dimensional CT scan showed persistent
      posterosuperior subluxation of the acromioclavicular joint and anatomical
      consolidation of the clavicular fracture. 

PMID- 27027061
TI  - SUPRA AND INTRACONDYLAR OPEN FRACTURE OF THE FEMUR IN A MOTOCROSS ATHLETE: CASE
      REPORT.
AB  - The authors report the case of a patient (amateur motocross competitor) who
      suffered a fall during a motocross competition resulting in a supra and
      intracondylar open fracture in the right femur. 

PMID- 27027062
TI  - SYNOVIAL CHONDROMATOSIS OF THE KNEE: CASE REPORT.
AB  - The authors report the case of a patient with synovial osteochondromatosis of the
      knee, who had previously been a soccer player. 

PMID- 27027064
TI  - What is your opinion?

PMID- 27027063
TI  - Dear Editor.

PMID- 27027065
TI  - BAKER'S CYST.
AB  - Baker's cysts are located in the posteromedial region of the knee between the
      medial belly of the gastrocnemius muscle and semimembranosus tendon. In adults,
      these cysts are related to intra-articular lesions, which may consist of meniscal
      lesions or arthrosis. In children, these cysts are usually found on physical
      examination or imaging studies, and they generally do not have any clinical
      relevance. Ultrasound examination is appropriate for identifying and measuring
      the popliteal cyst. The main treatment approach should focus on the joint
      lesions, and in most cases there is no need to address the cyst directly.
      Although almost all knee cysts are benign (Baker's cysts and parameniscal cysts),
      presence of some signs makes it necessary to suspect malignancy: symptoms
      disproportionate to the size of the cyst, absence of joint damage (e.g. meniscal
      tears) that might explain the existence of the cyst, unusual cyst topography,
      bone erosion, cyst size greater than 5 cm and tissue invasion (joint capsule). 

PMID- 27027066
TI  - PROPOSAL FOR STANDARDIZATION OF RADIOGRAPHIC STUDIES ON THE HIP AND PELVIS.
AB  - Diagnoses of hip and pelvis disorders are based on the detailed medical history,
      physical examination and laboratory tests, as appropriate for each condition.
      Plain radiography is still the initial examination of choice and, because of its
      importance, there is a need to standardize radiographic studies, both in relation
      to execution and in radiographic series, according to the different pathological
      conditions. The aim of this paper was to propose standardization for the main
      radiographic views of the hip and pelvis, and with regard to performing specific
      series for different pathological conditions, and to provide technical guidance
      for achieving these aims. 

PMID- 27027068
TI  - CLINICAL AND RADIOLOGICAL EVALUATION ON DEVELOPMENTAL HIP DYSPLASIA AFTER SALTER
      AND OMBREDANNE PROCEDURE.
AB  - OBJECTIVE: To evaluate the clinical and radiological medium-term results from
      surgical treatment of developmental hip dysplasia through Salter innominate bone
      osteotomy and Ombredanne femoral shortening. METHODS: Fourteen patients were
      evaluated, with surgical treatment on 18 hips (seven right-side hips and eleven
      left-side hips) using the proposal technique, performed between 1998 and 2008.
      The Dutoit and Severin criteria were used respectively for clinical and
      radiographic evaluations. RESULTS: The average preoperative index for the seven
      right-side hips was 43.3 degrees  (40 degrees  to 50 degrees ), and this was
      corrected through surgery to an average of 31.57 degrees  (24 degrees  to 42
      degrees ). The average preoperative index for the eleven left-side hips was 42.1
      degrees  (36 degrees  to 56 degrees ), and this was corrected through surgery to
      an average of 30.36 degrees  (20 degrees  to 44 degrees ). There was a
      statistically significant difference between the preoperative and postoperative
      acetabular indexes, with P > 0.05. The clinical evaluation showed that there were
      seven excellent hips (38.9%), eight good ones (44.4%), three fair hips (16.7%)
      and no poor ones (0%). By grouping the hips rated good and excellent as
      satisfactory and those rated poor and fair as unsatisfactory, 83.3% of the
      results were seen to be favorable. There were no statistically significant
      correlations between occurrences of complications and patient age at the time of
      surgery or between complications and the preoperative acetabular index (p >
      0.05). The complications observed consisted of one case each of subluxation,
      osteonecrosis and osteonecrosis together with subluxation. CONCLUSION: The
      combined procedure of Salter and Ombredanne is a viable option for treating
      developmental hip dysplasia after patients have started to walk.

PMID- 27027069
TI  - MECHANICAL STUDY ON DORSAL STABILITY OF INTRAMEDULLARY OSTEOSYNTHESIS ASSOCIATED
      WITH EXTERNAL FIXATION (ULSON'S METHOD).
AB  - OBJECTIVE: To evaluate the Ulson intramedullary fixation method, with external
      fixation in which the level of the external locking of the Kirschner wires is
      varied, and without external fixation. METHODS: Eighteen porcine tibias were
      used. Transverse osteotomy was performed in the region of the tuberosity, and two
      intramedullary Kirschner wires were inserted into each specimen, using three
      different assembly patterns: Group I: locking with external minifixator at a
      height of 3.0 cm; Group II: locking at a height of 4.5 cm; Group III: without
      external locking. Mechanical shear tests were then conducted, to determine the
      maximum load, proportionality limit and coefficient of rigidity. RESULTS: There
      were no significant differences in maximum load or proportionality limit between
      the groups. The coefficient of rigidity was higher in Group II. CONCLUSION: The
      locking height for the Kirschner wires in Ulson's method, within the limits
      evaluated, did not harm the stability of the fracture fixation system.

PMID- 27027067
TI  - PERIPHERAL NERVE REGENERATION: CELL THERAPY AND NEUROTROPHIC FACTORS.
AB  - Peripheral nerve trauma results in functional loss in the innervated organ, and
      recovery without surgical intervention is rare. Many surgical techniques can be
      used for nerve repair. Among these, the tubulization technique can be
      highlighted: this allows regenerative factors to be introduced into the chamber.
      Cell therapy and tissue engineering have arisen as an alternative for stimulating
      and aiding peripheral nerve regeneration. Therefore, the aim of this review was
      to provide a survey and analysis on the results from experimental and clinical
      studies that used cell therapy and tissue engineering as tools for optimizing the
      regeneration process. The articles used came from the LILACS, Medline and SciELO
      scientific databases. Articles on the use of stem cells, Schwann cells, growth
      factors, collagen, laminin and platelet-rich plasma for peripheral nerve repair
      were summarized over the course of the review. Based on these studies, it could
      be concluded that the use of stem cells derived from different sources presents
      promising results relating to nerve regeneration, because these cells have a
      capacity for neuronal differentiation, thus demonstrating effective functional
      results. The use of tubes containing bioactive elements with controlled release
      also optimizes the nerve repair, thus promoting greater myelination and axonal
      growth of peripheral nerves. Another promising treatment is the use of platelet
      rich plasma, which not only releases growth factors that are important in nerve
      repair, but also serves as a carrier for exogenous factors, thereby stimulating
      the proliferation of specific cells for peripheral nerve repair. 

PMID- 27027070
TI  - EPIDEMIOLOGICAL CHARACTERISTICS AND CAUSES OF PROXIMAL FEMORAL FRACTURES AMONG
      THE ELDERLY.
AB  - OBJECTIVE: The social and economic cost of proximal femoral fractures is high,
      due the morbidity and mortality relating to the fracture itself, among other
      factors. Despite the importance of this issue, studies on this topic are still
      scarce in Brazil. This was a retrospective, observational and cross-sectional
      (ecological) study with the aims of outlining an epidemiological profile for
      proximal femoral fractures among the elderly and analyzing the causes of these
      fractures and the physical characteristics of patients admitted to a single
      university hospital in Sao Paulo. METHODS: This was a study on medical records
      over a one-year period, with group comparisons using the chi-square test; p >
      0.05 was considered significant. RESULTS: Ninety-four individuals were evaluated:
      predominantly female (2:1); 81-85 years of age; body mass index within normal
      limits; white and Asian patients (p > 0.05). The vast majority of the fractures
      occurred through low-energy trauma and inside the patients' homes (p > 0.05).
      After excluding the trauma resulting from high-energy events, over 39% occurred
      as the patients were moving from sitting to standing up or were using stairs, and
      approximately 40% occurred while they were standing still or walking. A greater
      number of cases corresponded to the cold seasons of the year (p > 0.05);
      CONCLUSION: Most injuries occurred inside the patients' own homes and had low
      energy causes. Thus, some accidents might be avoided through simple low-cost
      measures that guide the elderly regarding situations of risk, which would bring
      major quality-of-life benefits and significant decreases in morbidity, mortality
      and the socioeconomic costs of this increasingly frequent problem.

PMID- 27027071
TI  - ANALYSIS ON THE MODIFIED LYSHOLM FUNCTIONAL PROTOCOL AMONG PATIENTS WITH NORMAL
      KNEES.
AB  - OBJECTIVE: To evaluate the modified Lysholm protocol among patients with knees
      that were considered to be normal (without previous complaints or pathological
      conditions in this region). METHOD: Between January 2010 and March 2010, a
      prospective study was conducted on 300 patients with orthopedic complaints in
      other regions of the body who came to the emergency service of our hospital. The
      inclusion criterion among these patients was the absence of complaints or
      previous surgery in the knee that was considered to be dominant. The age range
      was from 16 to 40 years, with an average of 28.8 years. Our study group consisted
      of 153 males and 147 females. In the modified Lysholm system, the maximum score
      is 100 points and this includes functional and objective criteria. Altogether,
      50% of the total score is based on symptoms of pain and instability. RESULTS: The
      average score using the Lysholm protocol was 95 points in the knees that were
      considered normal. Males had higher scores than females. CONCLUSION: These
      patients with knees that were considered normal did not achieve the maximum score
      when evaluated using the modified Lysholm protocol. This study suggests that this
      line of research on functional evaluation systems for the knee is open for
      further evaluations. Moreover, creation and development of new forms of
      functional assessment for the knee should be investigated in order to achieve a
      worldwide consensus.

PMID- 27027072
TI  - RANDOMIZED PROSPECTIVE STUDY ON TRAUMATIC PATELLAR DISLOCATION: CONSERVATIVE
      TREATMENT VERSUS RECONSTRUCTION OF THE MEDIAL PATELLOFEMORAL LIGAMENT USING THE
      PATELLAR TENDON, WITH A MINIMUM OF TWO YEARS OF FOLLOW-UP.
AB  - OBJECTIVE: The aim of this study was to compare the surgical results from
      reconstruction of the medial patellofemoral ligament (MPFL) with non-operative
      treatment of primary patellar dislocation. METHODS: Thirty-nine patients (41
      knees) with patellar dislocation were randomized into two groups. One group was
      treated conservatively (immobilization and physiotherapy) and other was treated
      surgically with reconstruction of the MPFL, and the results were evaluated with a
      minimum follow-up of two years. The Kujala questionnaire was applied to assess
      pain and quality of life, and recurrences were evaluated. Pearson's chi-square
      test and Fisher's exact test were used in the statistical evaluation. RESULTS:
      The statistical analysis showed that the mean Kujala score was significantly
      lower in the conservative group (70.8), compared with the mean value in the
      surgical group (88.9), with p = 0.001. The surgical group presented a higher
      percentage of "good/excellent" Kujala score results (71.43%) than in the
      conservative group (25.0%), with p = 0.003. The conservative group presented a
      greater number of recurrences (35% of the cases), while in the surgical group
      there were no reports of recurrences and/or subluxation. CONCLUSIONS: Treatment
      with reconstruction of the medial patellofemoral ligament using the patellar
      tendon produced better results, based on the analysis of post-treatment
      recurrences and the better final results from the Kujala questionnaire after a
      minimum follow-up period of two years.

PMID- 27027073
TI  - RESULTS FROM FILLING "REMPLISSAGE" ARTHROSCOPIC TECHNIQUE FOR RECURRENT ANTERIOR
      SHOULDER DISLOCATION.
AB  - OBJECTIVE: To evaluate the clinical result from the filling ("remplissage")
      technique in association with Bankart lesion repair for treating recurrent
      anterior shoulder dislocation. METHODS: Nine patients (10 shoulders), with a mean
      follow-up of 13.7 months, presented traumatic recurrent anterior shoulder
      dislocation. All of them had a Bankart lesion, associated with a Hill-Sachs
      lesion showing the "engaging" sign. The Hill-Sachs lesion defect was measured and
      showed an average bone loss of 17.3% (7.7% to 26.7%) in relation to the diameter
      of the humeral head. All the cases underwent arthroscopic repair of the Bankart
      lesion, together with filling of the Hill-Sachs lesion by means of tenodesis of
      the infraspinatus. RESULTS: The Rowe score ranged from 22.5 (10 to 45) before the
      operation to 80.5 (5 to 100) after the operation (p > 0.001). The UCLA score
      ranged from 18.0 (8 to 29) to 31.1 (21 to 31) (p > 0.001). The measurements of
      external and internal rotation at abduction of 90 degrees  after the operation
      were 63.5 degrees  (45 degrees  to 90 degrees ) and 73 degrees  (50 degrees  to
      92 degrees ) respectively. Two patients presented recurrence (one with
      dislocation and the other with subluxation). None of the patients presented pain
      in the region of the infraspinatus tendon after the operation. CONCLUSION: Over
      the short term, the filling ("remplissage") arthroscopic technique produced
      improvements in functional scores and a low complication rate when used for
      treating glenohumeral instability associated with Hill-Sachs lesions.

PMID- 27027074
TI  - "ROCAMBOLE-LIKE" BICEPS TENODESIS: TECHNIQUE AND RESULTS.
AB  - OBJECTIVE: To present a new technique for bicipital tenodesis and its results:
      accomplished partially via arthroscopy and grounded in concepts of the normal and
      pathological anatomy of the tendon of the biceps long head. It is based on the
      predisposition of this tendon towards becoming attached to the intertubercular
      sulcus after rupture or tenotomy (auto-tenodesis). METHODS: Evaluations were
      conducted on 63 patients (63 shoulders), aged from 32 to 77 years (average 55),
      consisting of 32 females (51%) and 31 males (49%). Thirty-five of the patients
      (55.6%) were over 60 years of age and 28 patients (44.4%) were under 60 years of
      age. Eighteen were sports participants (28.6%). Fourteen had injuries associated
      with the subscapularis (22.2%). The average follow up was 43 months (ranging from
      12 to 74 months). The right shoulder accounted for 48 cases (76.2%), of which one
      was a left-handed individual and 47 were right-handed. The left shoulder
      accounted for 15 (23%) of the patients, of whom two were left-handed and 13 were
      right-handed. There were no bilateral occurrences. The statistical analysis were
      done using SPSS version 18. Pearson's chi-square test and continuity corrections
      were used to investigate the statistical significance of associations between
      variables. Associations were taken to be statistically significant when p was
      less than 0.05. RESULTS: Residual Popeye deformity was perceived by seven
      patients (11.1%); it was only observed by the examiner in 15 cases (23.8%); and
      neither the patient nor the examiner observed it in 41 cases (65%). There were no
      statistically valid influences from age, participation in contact or throwing
      sports, subscapularis tendon-associated injury or Popeye deformity. Fifty-eight
      patients (92.06%) were satisfied, two patients were dissatisfied (3.17%) and
      three patients were indifferent (4.76%). CONCLUSION: The technique presented high
      patient satisfaction rates (92.06%) and residual deformity was perceived by 11.1%
      of the patients. The appearance did not have any statistically valid correlation
      with ages over or under 60 years (p = 0.883), sports practice (p = 0.195) or
      subscapularis-associated injury (p = 0.958).

PMID- 27027075
TI  - LOW-LEVEL LASER THERAPY AFTER CARPAL TUNNEL RELEASE.
AB  - OBJECTIVE: Evaluate the post-operative treatment of CTS, using the LLLT. METHOD:
      We prospectively evaluated 58 patients with CTS, randomly divided into two
      groups: treatment with LLLT (Group 1) and placebo (Group 2). A 830 nm gallium
      aluminum-arsenic laser was used, with a power of 30 mW. RESULTS: There was female
      predominance in both groups. The mean age of the patients in Group 1 was 44.3
      years and in Group 2, 51.9 years. The average duration of disease progression was
      around two years in both groups. The average time elapsed since discharge from
      treatment was 3.6 months in both groups, and fewer patients had postoperative
      complaints in Group 1 than in Group 2. At the end of the treatment, in Group 1,
      29.41% of the patients presented electromyographic abnormalities, while in Group
      2, 63.64% of the patients had abnormalities, after six months. CONCLUSION: This
      was an initial study on adjuvant therapy using postoperative LLLT on CTS. The
      method presented was sufficient for postoperative evaluation of the patients in
      this study. Patients undergoing LLLT after surgery for CTS were benefited and had
      better functional outcomes than shown by the control group. The technique was
      effective and did not have any adverse effects on the patients studied.

PMID- 27027076
TI  - TREATMENT OF OSTEOCHONDRAL LESIONS OF THE TALUS BY MEANS OF THEARTHROSCOPY
      ASSISTED MICROPERFORATION TECHNIQUE.
AB  - OBJECTIVE: To evaluate patients affected by osteochondral fractures of the talus
      who were treated surgically by means of arthroscopy-assisted microperforation.
      METHODS: A retrospective study was carried out on 24 patients with osteochondral
      lesions of the talus who underwent microperforation assisted by videoarthroscopy
      of the ankle. They were evaluated using the American Orthopaedic Foot and Ankle
      Society (AOFAS) score system before and after the operation. RESULTS: There were
      19 men and 5 women, with a mean age of 35.3 years (minimum of 17 years and
      maximum of 54 years). The minimum follow-up was two years (maximum of 39 months).
      All the patients showed an improvement in AOFAS score after surgery, with an
      average improvement of around 22.5 points. CONCLUSION: Videoarthroscopy-assisted
      microperforation is a good option for treating osteochondral lesions of the talus
      and provides good functional results.

PMID- 27027077
TI  - Strong orthopedists.

PMID- 27027078
TI  - UPDATING ON DIAGNOSIS AND TREATMENT OF CHONDRAL LESION OF THE KNEE.
AB  - The treatment of chondral knee injuries remains a challenge for the orthopedic
      surgeon, mainly owing to the characteristics of the cartilage tissue, which
      promote low potential for regeneration. Chondral lesions can be caused by
      metabolic stimulation, or by genetic, vascular and traumatic events, and are
      classified according to the size and thickness of the affected cartilage.
      Clinical diagnosis can be difficult, especially due to insidious symptoms.
      Additional tests, as Magnetic Resonance Imaging (MRI), may be needed. The
      treatment of these lesions usually starts with non-operative management. Surgery
      should be reserved for patients with detached chondral fragments, blocked range
      of motion, or the failure of non-operative treatment. The surgical techniques
      used for the treatment of partial thickness defects are Debridement and Ablation.
      These techniques aim to improve symptoms, since they do not restore normal
      structure and function of the cartilage. For full-thickness defects
      (osteochondral lesion), available treatments are Abrasion, Drilling,
      Microfracture, Osteochondral Autologous and Allogeneic Transplantation, and
      biological techniques such as the use of Autologous Chondrocyte Transplantation,
      Minced Cartilage and stem cells. 

PMID- 27027079
TI  - WHAT IS THE BEST RADIOGRAPHIC VIEW FOR "DIE PUNCH" DISTAL RADIUS FRACTURES? A
      CADAVER MODEL STUDY.
AB  - OBJECTIVE: the aim of this study is try to show the best view for distal radius
      fractures so called die-punch fractures. METHODS: There has been used a human
      cadaver radius bone from the Salvador Arena Tissue Bank. This bone was cleaned up
      after removing the soft tissues and osteotomies created displaced lunate fossa
      fractures of 0, 1, 2, 3 and 5 mm. We have fixed this fragment with adhesive tape.
      Then the joint deviation were significantly increased with step-offs of 1 mm.
      Radiographs were then taken into 5 different positions: postero-anterior view,
      lateral view, oblique views and tangencial view for each of the deviations. The
      resulting lunate fossa depression in each X-ray film was analyzed by the AutoCAD
      2010(r) software. RESULTS: The tangencial view was the best one to see the 1mm
      and 3mm bone degrees and the second one view to see the 2mm and 5 mm degrees. The
      pronated oblique view was the best to see the 2mm degrees and the oblique
      supinated view wasn't able to see the degrees between 1 and 2mm. CONCLUSION: The
      tangencial view was the best one to see the 1mm and 3mm bone degrees and the
      second one view to see the 2mm and 5 mm degrees.

PMID- 27027080
TI  - PROXIMAL FEMURAL VALGUS SUBTROCHANTERIC OSTEOTOMY FOR NON UNION OF TROCHANTERIC
      FRACTURES.
AB  - OBJECTIVES: To evaluate valgus subtrochanteric osteotomy for the treatment of
      trochanteric non-union. METHODS: A retrospective study of cases series. From 1998
      September to 2009 January, seventeen (17) cases with a diagnosis of non-union of
      trochanteric fracture were re-operated by the hip group of the Ortophaedic And
      Traumatology service of the Hospital Geral de Goiania (HGG). The patients
      presented pain at the fracture site, a femoral varus angle of less than 120
      degrees , and non-union of the fracture in the 3(rd) months after the initial
      surgery. RESULTS: Patients with ages ranging from 30 to 73 years, with a maximum
      follow-up of 09 years and minimum of 09 years. The mean time from first surgery
      to osteotomy was six months. Bone union was observed in 16 patients, with a mean
      union time of 12 weeks after surgery. The mean hip varus angle was 105(0) (120(0)
      to 90(0)). After surgery, the mean hip valgus angle was 144(0) (155(0) to
      135(0)). We had one unsuccessful case; a 78-year old patient who had osteogtomy,
      fixed with DHS of 150(0), with valgization to 154(0). After six months of follow
      up without union of the fracture, it was decided to perform total cemented hip
      artroplasthy, without complications. CONCLUSION: Valgus subtrochanteric
      osteotomies can be indicated for the treatment of trochanteric treatment of
      pseudoarthroses, with good final results for bone union, avoiding the need for
      total hip artroplasthy and maintaining biological fixation, as well as
      reestablishing the mechanical and anatomical axis of the affected limb.

PMID- 27027081
TI  - BIOMECHANICAL STUDY OF TRANSCORTICAL OR TRANSTRABECULAR BONE FIXATION OF PATELLAR
      TENDON GRAFT WITH BIOABSORBABLE PINS IN ACL RECONSTRUCTION IN SHEEP.
AB  - OBJECTIVE: To determine the initial resistance of fixation using the Rigid
      Fix((r)) system, and compare it with traditional fixation methods using metal
      interference screws; and to evaluate the resistance of the fixation with the
      rigid fix system when the rotational position of the bone block is altered in the
      interior of the femoral tunnel. METHODS: forty ovine knee specimens (stifle
      joints) were submitted to anterior cruciate ligament reconstruction (ACL) using a
      bone-tendon-bone graft. In twenty specimens, the Rigid Fix method was used; this
      group was subdivided into two groups: ten knees the pins transfixed only the
      spongious area of the bone block, and ten for fixation passing through the layer
      of cortical bone. In the twenty remaining specimens, the graft was fixed with 9mm
      metal interference screws. RESULTS: comparison of the RIGIDFIX((r)) method with
      the metal interference screw fixation method did not show any statistically
      significant differences in terms of maximum load and rigidity; also, there were
      no statistically significant differences when the rotational position of the bone
      block was altered inside the femoral tunnel. For these evaluations, a level of
      significance of p < 0.017 was considered. CONCLUSION: fixation of the bone-tendon
      bone graft with 2 bioabsorbable pines, regardless of the rotational position
      inside the femoral tunnel, gave a comparable fixation in terms of initial
      resistance to the metal interference screw, in this experimental model.

PMID- 27027082
TI  - COMPARATIVE STUDY OF ACL RECONSTRUCTION WITH ANATOMICAL POSITIONING OF THE
      TUNNELS USING THE PATELLAR TENDON VERSUS HAMSTRING TENDON.
AB  - OBJECTIVE: To compare ACL reconstruction with anatomical positioning of the
      tunnels using the hamstring or patellar tendons. METHODS: We prospectively
      evaluated 52 patients who underwent ACL reconstruction using the Chambat's
      technique, with anatomical positioning of the tunnels drilled outside in. They
      were divided into group A, with 27 patients, using the patellar tendon as a
      graft, and group B, with 25 patients, using the hamstring. RESULTS: In group A 26
      patients were very satisfied or satisfied and 1 unhappy, in group B. 25 patients
      were very satisfied or satisfied with the procedure (p = 0.990). According to the
      Lysholm scale, group A had a mean score of 96.11 and group B, 95.32 (p=0.594). In
      relation to preoperative IKDC, 100% of the patients in group A and 92% of those
      in group B were IKDC C or D (p = 0.221); in the assessment with a minimum of two
      year follow-up, 96% of group A and 92% of group B were IKDC A or B (p = 0.256).
      The Lachman test, pivot shift, return to sports activities, and the comparative
      difference in anterior translation (Rolimeter(TM)) also showed no statistically
      significant difference. In group A, 5 patients (18.5%) were unable to kneel on a
      hard surface, whereas no patient in group B had this complaint. CONCLUSION: The
      anterior cruciate ligament reconstruction presents similar results using the
      hamstring or patellar tendon with anatomical positioning of the tunnels. Drilling
      the femoral tunnel outside in is a reproducible and accurate option in the
      correct placement the femoral tunnel.

PMID- 27027083
TI  - POSTERIOR CRUCIATE LIGAMENT RECONSTRUCTION WITH AUTOGRAFT OF THE DOUBLE
      SEMITENDINOSUS MUSCLES AND MIDDLE THIRD OF THE QUADRICEPS TENDON WITH DOUBLE
      FEMORAL AND SINGLE TIBIAL TUNNELS: CLINICAL RESULTS IN TWO YEARS FOLLOW UP.
AB  - OBJECTIVE: To evaluate the surgical aspects that may offer good anatomic and
      functional results in posterior cruciate ligament (PCL) reconstruction using an
      autologous graft of the quadriceps tendon and double semitendinosus through a
      double femoral tunnel. METHODS: Fourteen patients with isolated PCL lesions,
      instability and pain were operated on by arthroscopy and evaluated according to
      the International Knee Documentation Committee (IKDC) and Lysholm scales.
      Posterior knee laxity was examined with a KT1000 arthrometer. RESULTS: The mean
      postoperative posterior side-to-side difference was between 0-2 mm in 57.1% of
      patients and between 3 and 5 mm in 35.7% of cases. The average Lysholm score was
      93 points in the final follow-up. In the IKDC evaluation, 3 patients were graded
      A, 10 were graded B, and 1 patient was graded C. CONCLUSIONS: Double bundle
      arthroscopic PCL reconstruction based on the anatomical positioning of the
      tunnels, with double semitendinosus tendon and single quadriceps, provides a
      clinically evident reduction in symptoms and restores satisfactory stability,
      although no statistically significant difference was found due to the small
      sample.

PMID- 27027084
TI  - PAIN AT THE TIP OF THE STEM AFTER REVISION TOTAL KNEE ARTHROPLASTY.
AB  - OBJECTIVE: To correlate parameters of implants with incidence of pain. METHODS:
      32 knees (31 patients) operated on between 2006 to 2008 in a serie of cases of
      TKA revision surgery were monitored for evidence of pain at the tip of the stem.
      In all we used uncemented stem Scorpio TS Total Knee (r) Revision System (Stryker
      (r)). Criteria assessed: pain in the leg or thigh without other causes, diameter
      and length of the nail; position of the rod in the medullary canal,
      intramedullary canal diameter. RESULTS: Mean age was 66.7 years and mean follow
      up was 2.6 years.21,87% of patients reported leg pain, 9.37% thigh pain. The
      group of pacients with leg pain presented with shaft diameter 14.7 mm, length 80
      mm in 71.42% and 155 mm in 28,58%, stem diameter/ intramedullary canal diameter
      average relation of 0,76, 42.8% had stem malalignment. The group without leg pain
      presented with shaft diameter 15.2 mm, length 80 mm in 68% and 155 mm in 32%,
      diameters average relation of 0.80, 20.8% had stem malalignment. The group with
      thigh pain presented with shaft diameter 18.3 mm, length 80 mm in 66.67% and 155
      mm in 33,33%,diameters average relation of 0.75, 0% had stem malalignment The
      group without thigh pain presented with shaft diameter 16.56 mm, length 80 mm in
      70.37% and 155 mm in 29,63%, diameters average relation of 0.79, 14,2% had stem
      malalignment. CONCLUSION: There was no association between the assessed criteria
      and pain in the tip of the stem.

PMID- 27027085
TI  - QUALITY OF LIFE AND SOCIAL CHARACTERISTICS OF PATIENTS SUBMITTED TO TOTAL KNEE
      ARTHROPLASTY.
AB  - OBJECTIVE: To study the quality of life (QL) and social characteristics of
      patients submitted to total knee arthroplasty (TKA). METHODS: The Brazilian
      validated version of the SF-36 Quality of Life Questionnaire was applied during
      the pre- and postoperative periods to assess the effect of TKA in QL. A semi
      structured social questionnaire was used for the survey of patients'
      socioeconomic profile. RESULTS: Some characteristics were observed in the
      participants' socioeconomic parameters, such as the predominance of females, age
      above sixty years old, family income up to three minimum salaries, patients'
      participation in family income, living together with other cohabitants,
      educational level up to high school; and living in urban periphery housing.
      Regarding SF-36, there was a statistically significant rise in corresponding
      values in postoperative assessment when compared with the preoperative assessment
      in all domains. CONCLUSION: TKA was capable of bringing a significant improvement
      in quality of life. In terms of social and economic profile of this group of
      patients submitted to TKA, it was observed that this profile was predominantly
      female, aged over sixty years, with low educational level, and limited economic
      resources.

PMID- 27027086
TI  - EFFECTIVENESS OF THE VIDEOARTHROSCOPY LEARNING PROCESS IN SYNTHETIC SHOULDER
      MODELS.
AB  - OBJECTIVES: The authors evaluate the learning of the videoarthroscopic technique,
      using the video surgery simulator SAM(r) (Shoulder Arthroscopy Model). METHODS:
      Twenty medical residents in Orthepaedics, without prior knowledge of the
      arthroscopic technique, were evaluated before and after training. The tasks
      consisted of positioning, in holes that simulated portals, four surgical threads
      attached to an anchor placed in the anatomical neck of the humerus in the
      synthetic model. Time, number of movements, number of attempts, amount of errors
      and comparison between the two phases of training before and after - were
      observed and noted. RESULTS: The data was submitted to statistical analysis, and
      a significant difference was found in the comparison of the variables before and
      after the training. CONCLUSION: The result of this study enables us to conclude
      that training in the videoarthroscopic technique using the video surgery
      simulator SAM enables the surgeon to execute essential tasks involved in these
      techniques, in less time, making less mistakes, and developing the ability to
      deal better with the videoarthrocopic image.

PMID- 27027087
TI  - BIOMECHANICS AND HISTOLOGICAL ANALYSIS IN RABBIT FLEXOR TENDONS REPAIRED USING
      THREE SUTURE TECHNIQUES (FOUR AND SIX STRANDS) WITH EARLY ACTIVE MOBILIZATION.
AB  - OBJECTIVE: Analyzing suture time, biomechanics (deformity between the stumps) and
      the histology of three groups of tendinous surgical repair: Brazil-2 (4-strands)
      which the end knot (core) is located outside the tendon, Indiana (4-strands) and
      Tsai (6-strands) with sutures technique which the end knot (core) is inner of the
      tendon, associated with early active mobilization. METHODS: The right calcaneal
      tendons (plantar flexor of the hind paw) of 36 rabbits of the New Zealand breed
      (Oryctolagus cuniculus) were used in the analysis. This sample presents similar
      size to human flexor tendon that has approximately 4.5 mm (varying from 2mm). The
      selected sample showed the same mass (2.5 to 3kg) and were male or female adults
      (from 8 1/2 months). For the flexor tendons of the hind paws, sterile and driven
      techniques were used in accordance to the Committee on Animal Research and Ethics
      (CETEA) of the University of the State of Santa Catarina (UDESC), municipality of
      Lages, in Brazil (protocol # 1.33.09). RESULTS: In the biomechanical analysis
      (deformity) carried out between tendinous stumps, there was no statistically
      significant difference (p>0.01). There was no statistical difference in relation
      to surgical time in all three suture techniques with a mean of 6.0 minutes for
      Tsai (6- strands), 5.7 minutes for Indiana (4-strands) and 5.6 minutes for Brazil
      (4-strands) (p>0.01). With the early active mobility, there was qualitative and
      quantitative evidence of thickening of collagen in 38.9% on the 15(th) day and in
      66.7% on the 30(th) day, making the biological tissue stronger and more resistant
      (p=0.095). CONCLUSION: This study demonstrated that there was no histological
      difference between the results achieved with an inside or outside end knot with
      respect to the repaired tendon and the number of strands did not affect healing,
      vascularization or sliding of the tendon in the osteofibrous tunnel, which are
      associated with early active mobility, with the repair techniques applied.

PMID- 27027088
TI  - COMPARATIVE STUDY OF THE EFFECTS OF LOW-LEVEL LASER AND LOW-INTENSITY ULTRASOUND
      ASSOCIATED WITH BIOSILICATE((r)) ON THE PROCESS OF BONE REPAIR IN THE RAT TIBIA.
AB  - OBJECTIVE: Verify the effects of the association between Biosilicate(r) and
      ultrasound and, Biosilicate(r) and laser in bone consolidation process of rats,
      through the biomechanical and histological analysis. METHODS: Forthy male rats
      were used. The animals were randomized into four groups (n=10): control group
      fracture no treated (CGF); group treated with Biosilicate(r) (BG); group treated
      with Biosilicate(r) and laser (BLG); group treated with Biosilicate(r) and
      ultrasound (BUG). RESULTS: The biomechanical analysis showed no significant
      difference among any groups after 14 days post-surgery. In the morphometric
      analysis, the control group showed moderate presence of new formed bone tissue
      inside the defects areas and the Biosilicate(r) group showed similar results.
      Despite those facts, the biomaterial osteogenic potential was demonstrated by the
      great amount of cells and bone tissue around the particles. Curiously, the
      Biosilicate(r) plus laser or ultrasound groups showed lower amounts of bone
      tissue deposition when compared with control fracture and Biosilicate(r) groups.
      CONCLUSION: The data from this study can conclude that Biosilicate(r) was able to
      accelerate and optimized the bone consolidation, through the modulation of the
      inflammatory process and the stimulation of new bone formation. However, when
      resources were associated, there are no positive results.

PMID- 27027090
TI  - THE MINUS((r)) SYSTEM MINIMALLY INVASIVE TECHNIQUE FOR THE TREATMENT OF
      TRANTROCHANTERIC FRACTURES.
AB  - The MINUS system was developed as a minimally invasive procedure that uses a
      diaphyseal cephalic extramedullary implant for the treatment of transtrochanteral
      fractures of the femur in elderly patients. The implant consists of a sliding
      screw coupled to a plate adapted to the minimally invasive technique. The
      surgical access is approximately three centimeters in length located on the
      lateral surface of the hip, below the projection of the small trochanter. A
      perfectly adapted instrument was used for the procedure, which also requires the
      use of an image intensifier, reducing surgery time and rate of bleeding. The
      objective of this study is to present a new instrument and implant, developed
      specifically for treatment with the minimally invasive technique, reducing the
      length of the conventional surgical access from 10 to three centimetres. This new
      implant was given the commercial name of MINUS System. 

PMID- 27027089
TI  - COMPARATIVE STUDY OF SPINAL AND LOCAL ANESTHESIA WITH PROPOFOL INFUSION FOR KNEE
      ARTHROSCOPY.
AB  - Spinal anesthesia for knee arthroscopy is a well-documented and safe procedure.
      However, some complications and higher costs have been reported. Also, many
      orthopaedic surgeons are reluctant to use local anesthesia for fear of having to
      convert to general anesthesia due to inadequate pain control. The purpose of this
      study is to compare local with spinal anesthesia in two groups of patients
      submitted to knee arthroscopy. Sixty-five patients were divided in two groups;
      based on the anesthesia method used, and submitted to the same surgical routine
      and postoperative analgesia protocol. They were evaluated for analgesia, level of
      postoperative pain, and level of satisfaction with the type of anesthetic. The
      two groups did not present any significant differences in relation to
      perioperative analgesia and pain on the first postoperative day, neither was
      there any difference in relation to emotional state. However, there was a
      significant difference in terms of acceptance of the procedure; 100% said they
      would accept the procedure again in the local anesthesia group, compared with
      60.5% in the spinal anesthesia group; also, 100% in the local anesthesia group
      said they felt encouraged by the type of anesthesia, compared with 67.7% in the
      spinal anesthesia group. We can conclude that local anesthesia is similar to
      spinal anesthesia in almost all the aspects investigated, except in terms of
      acceptance and patients' level of satisfaction with the procedure. Local
      anesthesia can be a good alternative to spinal anesthesia, especially in
      outpatient departments, or when patients have restrictions to traditional models
      of anesthesia. 

PMID- 27027091
TI  - RECONSTRUCTION FOLLOWING EXTENSIVE TUMOR RESECTION OF THE PELVIC AND SCAPULAR
      GIRDLE: A REPORT OF TWO CASES.
AB  - Radical surgeries for treatment of scapular and pelvic girdle tumors
      (hemipelvectomy and interscapulothoracic amputation) are generally extended
      procedures, with large areas of local tissue loss after tumor resection. The use
      of a flap that includes all the anterior and posterior thigh musculature after
      femur dissection, pedicled in the superficial femoral vessels, has been described
      was only once in the medical literature, and there have been no reports on a
      similar flap using the whole anterior and posterior musculature of the arm after
      humerus dissection, pedicled in the subclavian vessels, for reconstruction after
      interscapulothoracic amputation. Here, we describe two cases - one hemipelvectomy
      and one interscapulothoracicl amputation - using these two the flaps to close the
      defect. 

PMID- 27027092
TI  - PRIMARY LIPOSARCOMA OF THE LUMBAR SPINE: CASE REPORT.
AB  - We report a rare case of primary bone liposarcoma of the lumbar spine, for which
      only one case has been reported. A female patient, 60 years of age, with lumbar
      pain and left sciatalgy for six months. In the imaging exams, a destructive tumor
      was found in the L4 vertebral body, and magnetic resonance imaging (MRI) revealed
      a tumoral lesion with T1 hiposignal and T2 hypersignal. Histological diagnosis
      was difficult, and immunohistochemistry confirmed the diagnosis. Surgical
      treatment was performed with wide ressection, spinal cord decompression, and
      anterior and posterior fusion of L3 to L5 complemented by radiotherapy and
      chemotherapy. After three years, a computed tomography (CT) scan evidenced an
      expansive injury in the lung. Despite its rarity, liposarcoma should be
      considered in the differential diagnosis of sciatica and primary tumors of the
      spine. 

PMID- 27027093
TI  - Findings of a Four-Year Randomized Controlled Clinical Trial Comparing Two-Piece
      and One-Piece Zirconia Abutments Supporting Single Prosthetic Restorations in
      Maxillary Anterior Region.
AB  - The purpose of this randomized controlled study is to investigate the clinical
      results obtained over four years and incidence of complications associated with
      one- versus two-piece custom made zirconia anchorages, in single tooth implant
      supported restorations of the maxillary anterior region. Sixty-five patients,
      with a total of 74 missing maxillary teeth, were selected in the period from
      February 2007 to July 2010. Two different ways of custom made zirconia abutment
      and final prosthetic restoration were evaluated: a standard zirconia abutment
      associated with a pressed layer of lithium disilicate with an all-ceramic
      cemented restoration versus one-piece restoration with the facing porcelain fired
      and pressed straight to the custom made zirconia abutment. In 29 cases, the
      restoration consisted of an all-ceramic restoration for cementation (two pieces);
      in 45 cases the restoration was a screw-retained restoration (one piece). Three
      all-ceramic restorations broke during the observation time. Two one-piece
      restorations fractured after 26 months. At follow-up examination there were no
      significant differences between one-piece and two-piece groups regarding the PI,
      BI, and MBL. Awaiting studies with longer follow-up times, a careful conclusion
      is that zirconia anchorages for single-implant restorations seem to demonstrate
      good short-term technical and biological results. 

PMID- 27027094
TI  - Implications of an Incidental Pulmonary Arteriovenous Malformation.
AB  - Introduction. Pulmonary arteriovenous malformations (PAVMs) have been associated
      with life-threatening complications, such as stroke and massive hemoptysis, thus
      posing significant morbidity if left untreated. We report a case of an incidental
      finding of a PAVM in a trauma patient newly recognized to have suspected
      hereditary hemorrhagic telangiectasia (HHT). Case Description. A 34-year-old man
      with a history of recurrent epistaxis presented with a sudden fall associated
      with seizure-like activity. Trauma imaging showed a large subdural hematoma and,
      incidentally, a serpiginous focus within the right upper lobe with a prominent
      feeding artery consistent with a PAVM. The patient was diagnosed with a simple
      PAVM related to possible or suspected HHT, an autosomal dominant trait with age
      related penetrance. He underwent a pulmonary arteriography of the right upper and
      lower lobe with the use of a microcatheter system; however, the PAVM could not be
      visualized. Thus, he was managed medically. The patient was educated on the need
      for prophylactic antibiotics prior to dental procedures and surveillance imaging.
      Discussion. Our case highlights the importance of obtaining a complete past
      medical and family history in young patients with a history of recurrent
      epistaxis to elicit features of HHT. The diagnosis can be made clinically and
      directly affects family members, who would otherwise not receive appropriate
      screening. 

PMID- 27027095
TI  - Disseminated zoster with paresis in a multiple sclerosis patient treated with
      dimethyl fumarate.

PMID- 27027096
TI  - CNS accumulation of regulatory B cells is VLA-4-dependent.
AB  - OBJECTIVE: To investigate the role of very late antigen-4 (VLA-4) on regulatory B
      cells (Breg) in CNS autoimmune disease. METHODS: Experimental autoimmune
      encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B
      cells (CD19cre/alpha4(f/f)) by immunization with myelin oligodendrocyte
      glycoprotein (MOG) peptide (p)35-55 or recombinant human (rh) MOG protein. B-cell
      and T-cell populations were examined by flow cytometry and immunohistochemistry.
      Breg were evaluated by intracellular IL-10 staining of B cells and, secondly, by
      coexpression of CD1d and CD5. RESULTS: As previously reported, EAE was less
      severe in B-cell VLA-4-deficient vs control CD19cre mice when induced by rhMOG, a
      model that is B-cell-dependent and leads to efficient B-cell activation and
      antibody production. Paradoxically, B-cell VLA-4-deficient mice developed more
      severe clinical disease than control mice when EAE was induced with MOG p35-55, a
      B-cell-independent encephalitogen that does not efficiently activate B cells.
      Peripheral T-cell and humoral immune responses were not altered in B-cell VLA-4
      deficient mice. In MOG p35-55-induced EAE, B-cell VLA-4 deficiency reduced CNS
      accumulation of B but not T cells. Breg were detected in the CNS of control mice
      with MOG p35-55-induced EAE. However, more severe EAE in B-cell VLA-4-deficient
      mice was associated with virtual absence of CNS Breg. CONCLUSIONS: Our results
      demonstrate that CNS accumulation of Breg is VLA-4-dependent and suggest that
      Breg may contribute to regulation of CNS autoimmunity in situ. These observations
      underscore the need to choose the appropriate encephalitogen when studying how B
      cells contribute to pathogenesis or regulation of CNS autoimmunity.

PMID- 27027097
TI  - Severe exacerbation of relapsing-remitting multiple sclerosis after G-CSF
      therapy.

PMID- 27027098
TI  - VZV in biopsy-positive and -negative giant cell arteritis: Analysis of 100+
      temporal arteries.

PMID- 27027099
TI  - Impact factor for the International Journal of Computerized Dentistry.

PMID- 27027100
TI  - Zirconia crowns - the new standard for single-visit dentistry?
AB  - Zirconia crowns combine the advantages of metal restorations, such as minimally
      invasive tooth preparation and ease of cementation, with those of full ceramic
      crowns, such as low thermal conductivity and tooth color. With the introduction
      of a high-speed sintering procedure, it is possible to produce and cement
      zirconia crowns and small monolithic bridges in a Cerec Single Visit procedure.
      This new procedure is compared to established chairside methods. 

PMID- 27027101
TI  - 3D fitting accuracy evaluation of CAD/CAM copings - comparison with spacer design
      settings.
AB  - OBJECTIVES: The accuracy of computer-aided design/computer- aided manufacturing
      (CAD/CAM) systems is linked to their technical characteristics and reliability
      for manufacturing the restoration designed. The aim of this study was to compare
      the accuracy of fit of zirconia copings manufactured with different CAD/CAM
      systems and their capacity to conform to pre-established spacer design settings.
      METHODS: Sixty zirconia copings were manufactured by three CAD/CAM systems, with
      their spacers set as recommended by their manufacturer on occlusal, axial, and
      marginal surfaces. The 3D triple-scan optical technique was used to obtain a fit
      mapping and to analyze the marginal and axial accuracy of fit. The reliability of
      the 3D measurement method was estimated using intraclass correlation and
      repeatability coefficients. The preparation coping interface width results were
      statistically analyzed using non-parametric analysis (Kruskal-Wallis, one-way
      ANOVA, and Wilcoxon signedrank tests) (P < 0.05). RESULTS: The repeatability
      coefficient was 6, 8, and 15 MUm for axial, marginal, and occlusal interface
      width measurements, respectively. For the three systems tested, no differences
      were found in the marginal area of the copings studied, with a mean fitting
      accuracy ranging from 54.3 to 66.6 MUm interface width. Statistically significant
      differences between groups were observed for the fitting accuracy measured in
      axial and occlusal areas. With the spacers set in the different areas, mean fit
      measurements of the zirconia copings were significantly larger, with an increased
      fit width ranging from 30 to 73 MUm. SIGNIFICANCE: The three CAD/CAM systems
      evaluated allowed similar marginal accuracy but failed to reproduce the pre
      established spacer parameters, with larger spacing showing throughout.

PMID- 27027102
TI  - Understanding dental CAD/CAM for restorations - dental milling machines from a
      mechanical engineering viewpoint. Part A: chairside milling machines.
AB  - The dental milling machine is an important device in the dental CAD/CAM chain.
      Nowadays, dental numerical controlled (NC) milling machines are available for
      dental surgeries (chairside solution). This article provides a mechanical
      engineering approach to NC milling machines to help dentists understand the
      involvement of technology in digital dentistry practice. First, some technical
      concepts and definitions associated with NC milling machines are described from a
      mechanical engineering viewpoint. The technical and economic criteria of four
      chairside dental NC milling machines that are available on the market are then
      described. The technical criteria are focused on the capacities of the embedded
      technologies of these milling machines to mill both prosthetic materials and
      types of shape restorations. The economic criteria are focused on investment
      costs and interoperability with third-party software. The clinical relevance of
      the technology is assessed in terms of the accuracy and integrity of the
      restoration. 

PMID- 27027103
TI  - Digital Michigan splint - from intraoral scanning to plasterless manufacturing.
AB  - AIM: To investigate whether the fully digital, plasterless fabrication of
      clinically usable Michigan splints can be accomplished in a time- and cost
      efficient manner. MATERIALS AND METHODS: Digital scans of the maxillary and
      mandibular arches of 10 subjects were acquired with an intraoral scanner (3Shape,
      Copenhagen) and used to generate virtual models of the dental arches. Jaw
      relation records were made using jigs placed on the subjects' anterior teeth, and
      silicone registration material was referenced to the jaw models. The data sets
      were then sent via the company's online portal to the dental laboratory, where
      computer-aided design (CAD) of the Michigan-type maxillary splints was performed.
      After receiving the designs, the splints were milled in-office using computer
      aided manufacturing (CAM) software, and finished manually. During try-in, the
      splints where checked for fit, retention quality, and occlusal contacts of the
      mandibular teeth on the splint surfaces in static and dynamic occlusion. RESULTS:
      Fit and retention were clinically acceptable in 10 splints and 9 splints,
      respectively. The number of initial occlusal contacts on the splint surfaces
      ranged from 4 to 16. CONCLUSIONS: The question addressed in this study can be
      answered in the affirmative. Some of the main advantages of digital manufacturing
      of Michigan splints over traditional, conventional, impression-based
      manufacturing are the time-efficient manufacturing process, the high material
      quality, and the possibility of manufacturing duplicate splints.

PMID- 27027104
TI  - Canine guidance via Biogeneric Copy: a clinical report.
AB  - The advent of computer-aided design/computer-aided manufacturing (CAD/CAM)
      technology in dentistry has enabled a wide range of applications. The Cerec
      Acquisition Center (Cerec AC, Sirona Dental Systems Inc., Charlotte, NC) allows
      for the construction of all-porcelain restorations, either in-office or through a
      remote dental laboratory. One feature of the Cerec AC is its ability to duplicate
      the dental morphology of an existing tooth onto a new CAD/CAM ceramic restoration
      designed for that tooth. This design mode capability of the Cerec AC is termed
      Biogeneric Copy. This function has been discussed in the literature where it has
      been utilized to fabricate a CAD/CAM ceramic crown to fit an existing removable
      partial denture (RPD).1-3 There are occasions in dentistry where the exact
      anatomy and position of an existing tooth, not associated with an RPD, should
      ideally be replicated in a definitive restoration. This case report describes
      such an occasion. 

PMID- 27027105
TI  - Rational design of multifunctional small-molecule prodrugs for simultaneous
      suppression of cancer cell growth and metastasis in vitro and in vivo.
AB  - We present a design concept for multifunctional prodrugs that simultaneously
      induce apoptosis and suppress cancer cell metastasis in vitro and in vivo. These
      "all-in-one" prodrug constructs possess therapeutic potential as novel
      "integrative" platforms for metastatic cancer treatment. 

PMID- 27027106
TI  - Formation of alpha-chalcogenyl acrylamides through unprecedented chalcogen
      mediated metal-free oxyfunctionalization of ynamides with DMSO as an oxidant.
AB  - A novel chalcogen-mediated oxyfunctionalization mode of ynamides for the
      synthesis of alpha-chalcogenyl acrylamides has been developed. Independent of
      metal catalysts, external oxidants and additives, this mild process afforded a
      range of structurally diverse alpha-chalcogenyl acrylamides, including alpha
      selanyl acrylamides and alpha-tellanyl acrylamides. Interestingly, diverse
      ynamides tolerated in this approach gave different stereoselectivities. 

PMID- 27027107
TI  - Orientation-selective alignments of nanoblocks in a and c directions of a
      tetragonal system through molecularly mediated manipulation.
AB  - Tetragonal Mn3O4 nanocuboids were aligned in selective crystallographic
      directions by molecularly mediated manipulation. Alignment in the a direction was
      produced by a face-by-a face assembly of hydrophobic nanocuboids covered with
      oleic acid. Another 1D array in the c direction was obtained through c face-to-c
      face assembly with the replacement of the organic modifiers. 

PMID- 27027109
TI  - Special report: youth & HIV risk.  Minority MSM population key part of growing
      epidemic in teens.  New biomedical prevention is needed.

PMID- 27027108
TI  - Fine-tuning of microsolvation and hydrogen bond interaction regulates substrate
      channelling in the course of flavonoid biosynthesis.
AB  - In the course of metabolite formation, some multienzymatic edifices, the so
      called metabolon, are formed and lead to a more efficient production of these
      natural compounds. One of the major features of these enzyme complexes is the
      facilitation of direct transfer of the metabolite between enzyme active sites by
      substrate channelling. Biophysical insights into substrate channelling remain
      scarce because the transient nature of these macromolecular complexes prevents
      the observation of high resolution structures. Here, using molecular modelling,
      we describe the substrate channelling of a flavonoid compound between DFR
      (dihydroflavonol-4-reductase) and LAR (leucoanthocyanidin reductase). The
      simulation presents crucial details concerning the kinetic, thermodynamic, and
      structural aspects of this diffusion. The formation of the DFR-LAR complex leads
      to the opening of the DFR active site giving rise to a facilitated diffusion, in
      about 1 MUs, of the DFR product towards LAR cavity. The theoretically observed
      substrate channelling is supported experimentally by the fact that this
      metabolite, i.e. the product of the DFR enzyme, is not stable in the media.
      Moreover, along this path, the influence of the solvent is crucial. The
      metabolite remains close to the surface of the complex avoiding full solvation.
      In addition, when the dynamic behaviour of the system leads to a loss of
      interaction between the metabolite and the enzymes, water molecules through
      bridging H-bonds prevent the former from escaping to the bulk.

PMID- 27027110
TI  - Researchers must reach out to youth in trials.  Address transportation problems,
      use multimedia.

PMID- 27027111
TI  - Abstinence study finds risk reduction.  Health care reform bill includes
      abstinence funding.

PMID- 27027112
TI  - HIV surveillance data lack demographics. Without it, clinicians are missing part
      of picture.

PMID- 27027114
TI  - Searching for the genie in the genome.  HIV human genomics field evolving at warp
      speed.

PMID- 27027113
TI  - Obama warns of 'declining sense of urgency' on HIV.  White House releases
      national HIV/AIDS strategy.

PMID- 27027115
TI  - FDA notifications.  Zidovudine injection approved as generic.

PMID- 27027116
TI  - FDA notifications.  Tentative OK for lamivudine, stavudine fixed dose combo.

PMID- 27027117
TI  - FDA notifications.  Generic abacavir sulfate tablets approved.

PMID- 27027118
TI  - Game on: athletes, researchers reach youth with active education. Kids retain
      knowledge after games like 'HIV Attack'.

PMID- 27027119
TI  - Ball game shows kids how HIV attacks.  Immune system tries to fight with no
      hands.

PMID- 27027122
TI  - Special focus: occupational HIV in the emergency room.

PMID- 27027120
TI  - Research suggests new path to HIV prevention.  Drug concentrations high in rectal
      tissue.

PMID- 27027121
TI  - Drug concentrations as measure of ART adherence. 'Adherence is far less that what
      people reported'.

PMID- 27027123
TI  - Abstract & commentary.  Treatment update: HIV and HCV co-infection.

PMID- 27027124
TI  - FDA notifications.  Generic zidovudine injection approved.

PMID- 27027126
TI  - Stigma: barrier to quality of life and health care.

PMID- 27027125
TI  - Histoplasmosis can be severe for HIV-infected persons in endemic areas.

PMID- 27027127
TI  - Clinically significant drug interactions in the HIV-infected elderly.

PMID- 27027128
TI  - HIV-infected adolescents have multiple risk factors for mental illness.

PMID- 27027129
TI  - Low health literacy predicts poor adherence.

PMID- 27027130
TI  - Peanuts can be important part of the diet for HIV-infected patients.

PMID- 27027131
TI  - Arkansas AETC takes aim at Native American health disparities.

PMID- 27027132
TI  - Commentary on Cheatham et al, "Postoperative  Rehabilitation After Hip
      Arthroscopy:  A Search for the Evidence".

PMID- 27027133
TI  - A fire with global connections.

PMID- 27027134
TI  - Anindya Dutta.

PMID- 27027135
TI  - The Problem with Change.

PMID- 27027136
TI  - Lessons We Can Learn From Tragic Event.

PMID- 27027137
TI  - Oklahoma "Tobacco Stops with Me" Media Campaign Effects on Attitudes toward
      Secondhand Smoke.
AB  - IMPORTANCE: Public education campaigns in tobacco control play an important role
      in changing tobacco-related knowledge, attitudes and behaviors. The Oklahoma
      Tobacco Stops with Me campaign has been effective in changing attitudes overall
      and across subpopulations towards secondhand smoke risks. OBJECTIVE: Investigate
      campaign impact on secondhand smoke policy and risk attitudes. DESIGN: Serial
      cross-sectional data analyzed with univariate and multivariable models. SETTING:
      Random-digit dialing surveys conducted in 2007 and 2015 PARTICIPANTS: Oklahomans
      18-65 years old Main Outcomes and Measures: (1) Support for smokefree bars; (2)
      risk assessment of secondhand smoke (very harmful, causes heart disease, causes
      sudden infant death); and 3) likelihood of protecting yourself from secondhand
      smoke. RESULTS: With Tobacco Stops with Me exposure, from 2007 to 2015,
      Oklahomans demonstrated significant increases in: (1) supporting smokefree bars
      (23.7% to 55%); (2) reporting beliefs that SHS causes heart disease (58.5% to
      72.6%), is very harmful (63.8% to 70.6%) and causes sudden infant death (24% to
      34%); and 3) reporting they are very likely to ask someone not to smoke nearby
      (45% to 52%). Controlling for demographics, smokers and males showed reduced
      attitude change. In uncontrolled comparisons, high-school graduates faired better
      than non-diploma individuals, who lacked significant attitude changes.
      CONCLUSIONS AND RELEVANCE: Tobacco Stops with Me achieved its mission to more
      closely align public perception of SHS with well-documented secondhand smoke
      risks. Efforts to target women were particularly successful. Smokers may be
      resistant to messaging; closing taglines that reinstate individual choice may
      help to reduce resistance/reactance (e.g., adding Oklahoma Helpline contact
      information).

PMID- 27027138
TI  - Surgical Care Processing in Major Oklholma City Hosptal: The Surgeons'
      Perspective.
AB  - PURPOSE: This study aimed to assess processing of surgical care provided at major
      Oklahoma City hospitals based on surgeons'perception. METHODS: A questionnaire
      was sent out to Oklahoma County Medical Society surgeons using survey monkey to
      assess surgeons' perception of surgical care provided by major hospitals in
      Oklahoma City metropolitan area. The email contained a short introduction of
      study and the general aim of the study. Student t test was applied to compare
      groups mean. P value <0.05 was considered significant. RESULTS: 79 valid
      responses were identified. 25% of surgeons scored that their patients waited in
      the post-op recovery area between 31-60 minutes before they were roomed, with a
      90% surgeon satisfaction rate. Compared to the longer waiting times this
      satisfaction rate was significantly higher (P < 0.0001). 64.6% of surgeons
      reported 31-60 minutes turn-over time between cases with only an 8% satisfaction
      rate. 10-30 minutes turnover time was reported in 13.9% of participants with
      72.7% satisfaction rate which was significant when compared to the former group.
      The surgeons scored that their patients presented to the hospital 1-2 hours
      before surgery 55.7% of the times and 92.7% of the surgeons were satisfied with
      this process (P < 0.0001). CONCLUSION: Surgeons'satisfaction increases with
      decreased patients processing times.

PMID- 27027139
TI  - The Dr. Harrison at Muskogee VAH, 1971.

PMID- 27027140
TI  - Football Safety. "We Must Change the Way the Game is Played".

PMID- 27027142
TI  - PRESIDENT'S PAGE.

PMID- 27027141
TI  - It is ALWAYS About the Patient....

PMID- 27027143
TI  - Porphyria or Catatonia: Diagnostic Dilemma on the Medical Wards.
AB  - A 24-year-old Caucasian female, DD, was admitted to the medical service at an
      academic hospital with symptoms of weakness in bilateral lower extremities,
      falls, headaches, and altered mental status. Psychiatry was consulted to evaluate
      for psychiatric causes of her symptoms. This case presented a diagnostic
      challenge as the patient's identified symptoms changed almost daily, depending on
      what practitioner or medical service she encountered. In this study, we discuss
      the differential diagnoses, tests and treatments the patient received, with a
      review of literature helping differentiate between diagnostic parameters.

PMID- 27027144
TI  - Metastatic Lung Carcinoma Involving the Maxillary Gingiva.
AB  - Metastatic spread of malignant tumors to the oral soft tissue is rare and account
      for 0.1% of all oral malignancies. Metastatic spread to the oral soft tissue can
      present as dental infections, which in turn can create a diagnostic challenge.
      Metastasis to the oral soft tissue from lung cancer is a rare situation. Here we
      describe a 52 year-old male patient treated initially with antibiotics for
      presumed oral abscess, who later was found to have metastatic lung cancer
      involving the maxillary gingiva.

PMID- 27027145
TI  - Problems with Prescribing Opioids? Read This!

PMID- 27027146
TI  - How Did We Get Here?

PMID- 27027147
TI  - Photoinduced and Thermal Relaxation in Surface-Grafted Azobenzene-Based
      Monolayers: A Molecular Dynamics Simulation Study.
AB  - Extensive atomistic molecular dynamics simulations have been employed to study
      the structure and molecular orientational relaxation of azobenzene-based
      monolayers grafted to a solid substrate. Systems with surface coverage of 0.6
      nm(2)/molecule were investigated over a wide temperature range ranging from 298
      K, where the mesogens show local ordering and the monolayer dynamics was found to
      be glassy, up to 700 K, where the azobenzene groups have a nearly isotropic
      orientational distribution, with a subnanosecond characteristic orientational
      relaxation time scale. Biased simulations that model single-molecule thermal
      excitation and conformational isomerization have been conducted to obtain insight
      into the mechanisms for photoinduced athermal fluidization and monolayer
      reorganization observed experimentally in this system. Our simulations clearly
      indicate that trans-cis conformational isomerization transitions of azobenzene
      units can lead to reorientation of mesogens and to the formation of a monolayer
      with strong macroscopic in-plane nematic order. While local heating created by
      excitation process can facilitate this process, thermal excitation alone is not
      sufficient to induce ordering in the monolayer. Instead, the work done by a
      molecule undergoing cis-trans isomerization on the cage of neighboring molecules
      is the key mechanism for photofluidization and orientational ordering in dMR
      monolayers exposed to linearly polarized light leading to relaxation dynamics
      that can be described in terms of higher effective temperature. The obtained
      simulation results are discussed in light of recent experimental data reported
      for these systems.

PMID- 27027148
TI  - In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano
      decorated subconjunctival implants.
AB  - Biodegradable implants are promising drug delivery systems for sustained release
      ocular drug delivery with the benefits such as minimum systemic side effects,
      constant drug concentration at the target site and getting cleared without
      surgical removal. Dry eye syndrome (DES) is a common disease characterized with
      the changes in ocular epithelia surface and results in inflammatory reaction that
      might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is
      frequently employed for the treatment of DES and it needs to be applied several
      times a day in tear drops form. The aim of this study was to evaluate in vivo
      behavior and efficacy of the developed nano-decorated subconjunctival implant
      systems for sustained release CsA delivery. Biodegradable Poly-E-caprolactone
      (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co
      glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve
      sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were
      selected for in vivo evaluation based on their in vitro characteristics
      determined in our previous study. In this study, formulations were implanted to
      Swiss Albino mice with induced dry eye syndrome to investigate the ocular
      distribution of CsA following subconjunctival implantation and to evaluate the
      efficacy. Tissue distribution study indicated that CsA was present in ocular
      tissues such as cornea, sclera and lens even 90 days after the application and
      blood CsA levels were found lower than ocular tissues. Efficacy studies also
      showed that application of CsA-loaded fiber implant formulation resulted in
      faster recovery based on their staining scores.

PMID- 27027150
TI  - Combination dabrafenib and trametinib in the management of advanced melanoma with
      BRAFV600 mutations.
AB  - INTRODUCTION: In the 40-50% of advanced melanoma patients with tumors harboring
      BRAF V600E and V600 K mutations, BRAF inhibitors such as dabrafenib are a highly
      effective treatment. However, most patients develop resistance after several
      months on treatment. The addition of a MEK inhibitor, such as trametinib, to BRAF
      inhibition mitigates one key pathway of resistance, further increasing response
      rates and improving survival. AREAS COVERED: This article summarizes the
      mechanism of action of the combination of dabrafenib and trametinib, its
      evolution through Phase I, II and III clinical trials and discusses its current
      use in the management of patients with advanced melanoma. EXPERT OPINION:
      Combination therapy with dabrafenib and trametinib improves response rate,
      progression-free survival and overall survival when compared to dabrafenib or
      vemurafenib alone. The addition of trametinib to dabrafenib changes the adverse
      event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less
      common but side effects such as fever and nausea more common. How
      dabrafenib/trametinib is best sequenced with other effective treatments such as
      immune checkpoint blockade remains uncertain.

PMID- 27027149
TI  - Traceless Production of Cyclic Peptide Libraries in E. coli.
AB  - Split intein circular ligation of peptides and proteins (SICLOPPS) is a
      genetically encoded method for the intracellular production of cyclic peptide
      libraries of around 100 million (10(8)) members that utilizes the Synechocystis
      sp PCC6803 (Ssp) DnaE split inteins. However, Ssp inteins are relatively slow
      splicing and intolerant of amino acid variation around the splice junction,
      potentially limiting the utility and composition of SICLOPPS libraries. In
      contrast, Nostoc punctiforme (Npu) DnaE split inteins not only splice
      significantly faster, they are also much more tolerant of amino acid variation
      around their splice junctions. Here, we report the use of engineered Npu inteins
      in SICLOPPS for the generation of cyclic peptide libraries and cyclic proteins.
      Despite their superior splicing characteristics, however, we observed a high
      level of toxicity from the Npu SICLOPPS constructs in E. coli. The observed
      toxicity was overcome though incorporation of an SsrA tag to target the spliced
      Npu inteins to the ClpXP complex for degradation. The resulting traceless Npu
      SICLOPPS inteins showed no toxicity to E. coli, demonstrating their potential for
      the production of cyclic peptide libraries for use in a variety of high
      throughput screens.

PMID- 27027151
TI  - Insulin Pump Malfunction During Hospitalization: Two Case Reports.
AB  - BACKGROUND: Insulin pump malfunctions and failures continue to occur; however,
      more severe malfunctions such as the "runaway pump" phenomenon are rarely
      reported. This article describes two cases of pump malfunction in which pump
      users appear to have received an unsolicited bolus of insulin resulting in severe
      episodes of hypoglycemia during hospitalization. MATERIALS AND METHODS: Both
      cases of insulin pump malfunction occurred in the inpatient setting at a large
      academic medical center in the United States. An analysis of the corresponding
      insulin pump downloads was performed. The Food and Drug Administration's (FDA's)
      Manufacturer and User Facility Device Experience (MAUDE) database was searched
      for similar cases involving Medtronic (Northridge, CA) insulin pumps using the
      terms "pump," "infusion," "insulin AND malfunction AND Medtronic." RESULTS: The
      two cases described show remarkable similarities, each demonstrating a severe
      hypoglycemic event preceded by an infusion site change followed by an alarm. In
      both cases a rapid spraying of insulin was reported. The insulin pump downloads
      validated much of the patients' and medical staff's descriptions of events. The
      FDA's MAUDE database search revealed 425 cases meeting our search term criteria.
      All cases were reviewed. Seven cases were identified involving independent
      movement of the reservoir piston. CONCLUSIONS: The cases detailed are the first
      to describe an insulin pump malfunction of this nature in the hospital setting
      involving unsolicited insulin boluses leading to severe hypoglycemia. The cases
      are particularly compelling in that they were witnessed by medical personnel.
      Providers and patients should receive instruction education on the recognition
      and management of insulin pump malfunction.

PMID- 27027153
TI  - Improving access to CPD is absolutely vital.

PMID- 27027154
TI  - Revalidation 'doomed to fail' if staff receive no support for CPD.

PMID- 27027152
TI  - Characterization of drug and alcohol use among senior drivers fatally injured in
      U.S. motor vehicle collisions, 2008-2012.
AB  - OBJECTIVE: Adults 65 years of age and older comprise the fastest growing
      demographic in the United States. As substance use is projected to increase in
      this population, there is concern that more seniors will drive under the
      influence of impairing drugs. The purpose of this analysis was to characterize
      the drug and alcohol usage among senior drivers fatally injured (FI) in traffic
      collisions. METHODS: Data from the Fatality Analysis Reporting System were
      analyzed from 2008 to 2012. Commonly used classes and specific drugs were
      explored. Rates of drug use, multiple drugs, concomitant drug and alcohol use,
      and alcohol use alone were generated using Poisson regression with robust error
      variance estimation. Rates were compared to a reference population of FI middle
      aged drivers (30 to 50 years old) using rate ratios. RESULTS: Drug use among FI
      senior drivers occurred in 20.0% of those tested. Among drug-positive FI senior
      drivers, narcotics and depressants were frequent. The prevalence of testing
      positive for any drug, multiple drugs, combined drug and alcohol, and alcohol use
      alone among FI seniors were 47% less (relative risk [RR] = 0.53, 95% confidence
      interval [CI], 0.47, 0.62), 59% less (RR = 0.41, 95% CI, 0.34, 0.51), 87% less
      (RR = 0.13, 95% CI, 0.09, 0.19), and 77% less (RR = 0.23, 95% CI, 0.19, 0.28),
      respectively, compared to FI middle-aged drivers. CONCLUSIONS: Though overall
      drug use is less common among FI senior drivers relative to FI middle-aged
      drivers, driving under the influence of drugs may be a relevant traffic safety
      concern in a portion of this population.

PMID- 27027155
TI  - Early birds prove revalidation success, says NMC.

PMID- 27027156
TI  - Queen's nurses to benefit from 90th birthday proceeds.

PMID- 27027157
TI  - Trial pilots will replace out-of-hours doctors with nurse practitioners.

PMID- 27027158
TI  - DH told to fix UK personnel shortfall while non-EU staff can plug the gap.

PMID- 27027159
TI  - 'Nurses for Hillary' in US presidency.

PMID- 27027161
TI  - NICE ruling widens cancer drug access.

PMID- 27027162
TI  - Welsh partnership extends end of life care at home.

PMID- 27027163
TI  - Type 2 diabetes programme allows nurses to refer those patients at risk.

PMID- 27027164
TI  - 'Never events' manual published.

PMID- 27027171
TI  - Domestic violence.

PMID- 27027172
TI  - 10 things you need to do for revalidation.

PMID- 27027165
TI  - Nurses may fall at revalidation's first hurdle without CPD support.

PMID- 27027173
TI  - Afraid of revalidation? Let us put you at ease.
AB  - Nurses outside the larger trusts may have worries about revalidation, such as who
      to have the reflective discussion with and how they will fulfil the CPD
      requirements. Evidence from the pilots suggests that these challenges can be
      overcome surprisingly easily.

PMID- 27027184
TI  - Quit for You Quit for Two app.

PMID- 27027186
TI  - Pay is now so behind, it's time to take a leaf out of the junior doctors' book.

PMID- 27027187
TI  - It is essential to address the low status of nursing in health care.

PMID- 27027188
TI  - Assaults on staff should never be tolerated by management.

PMID- 27027189
TI  - Health promotion is an area of practice that is often neglected.

PMID- 27027190
TI  - Where were nurses' protests against cruel benefits cuts?

PMID- 27027191
TI  - Shareholder-driven private providers discredit the NHS.

PMID- 27027195
TI  - How to alleviate perineal pain following an episiotomy.

PMID- 27027196
TI  - Nurses' attitudes towards patients hospitalised for self-harm.
AB  - Self-harm is a public health issue that accounts for thousands of presentations
      at hospital each year. Self-harm commonly involves self-injury by cutting,
      burning or poisoning. The incidence of self-harm is increasing in the UK,
      particularly in young people. Research suggests that people who self-harm
      experience negative attitudes from healthcare staff, including nurses, on
      presentation to healthcare services. This is an ethical issue in nursing practice
      that has implications for the quality of care provided. Nurses with a lack of
      mental health training provide care for patients who self-harm in emergency
      departments and acute medical settings. This article presents a literature review
      exploring the factors affecting nurses' attitudes towards patients hospitalised
      for self-harm and makes recommendations for improving practice. The article
      identifies requirements for nurse education and training in mental health and
      effective provision of care for patients who self-harm and present at the
      emergency department. 

PMID- 27027197
TI  - Human factors and the death of a child in hospital: a case review.
AB  - Learning from adverse events and errors is important if systems and processes are
      to be improved and to minimise the likelihood of similar events in the future.
      This article uses the report from a coroner's inquest into the death of a seven
      year-old child in hospital to examine errors that contributed to the child's
      death. These errors are reviewed from a human factors perspective. The article
      provides an overview of error causation concepts and offers strategies that
      healthcare organisations can implement to reduce the incidence of such errors. 

PMID- 27027198
TI  - Rosacea: clinical features and treatment.
AB  - Rosacea is a chronic inflammatory skin condition that predominantly affects the
      central face. It is characterised by a variable range of symptoms, including
      erythema, telangiectasia, papules, pustules and changes in skin texture. Rosacea
      may be transient, recurrent or persistent. Because it affects the most visible
      part of the body, the psychosocial effects of this condition can be significant.
      This article describes the features and management of the condition. 

PMID- 27027199
TI  - Constipation.

PMID- 27027200
TI  - Make the right choice.

PMID- 27027201
TI  - Expanding skills and experience.

PMID- 27027203
TI  - Make your voice heard.

PMID- 27027204
TI  - N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized,
      Double-Blind, Placebo-Controlled Add-On Trial.
AB  - BACKGROUND: Current pharmacological treatments for Tourette Syndrome (TS), such
      as antipsychotic agents and alpha-2 agonists, are moderately effective in the
      treatment of tics, but have substantial side effects that limit their use. N
      acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as
      an antioxidant agent with minimal side effects for decades. NAC has been
      increasingly studied for the treatment of other obsessive-compulsive spectrum
      disorders. We aim to examine the efficacy of NAC for the treatment of pediatric
      TS in a double-blind, placebo-controlled, add-on study. METHODS: Thirty-one
      children and adolescents 8-17 years of age with TS were randomly assigned to
      receive NAC or matching placebo for 12 weeks. Our primary outcome was change in
      severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total
      tic score. Secondary measures assessed comorbid obsessive-compulsive disorder
      (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD).
      Linear mixed models in SAS were used to examine differences between NAC and
      placebo. RESULTS: Of 31 randomized subjects, 14 were assigned to placebo (two
      females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years)
      treatment. No significant difference between NAC and placebo was found in
      reducing tic severity or any secondary outcomes. CONCLUSIONS: We found no
      evidence for efficacy of NAC in treating tic symptoms. Our findings stand in
      contrast to studies suggesting benefits of NAC in the treatment of other
      obsessive-compulsive spectrum disorders in adults, including OCD and
      trichotillomania, but are similar to a recent placebo-controlled trial of
      pediatric trichotillomania that found no benefit of NAC.

PMID- 27027205
TI  - Influence of Peri-Operative Hypothermia on Surgical Site Infection in Prolonged
      Gastroenterological Surgery.
AB  - BACKGROUND: There have been several recent studies on the correlation between
      intra-operative hypothermia and the occurrence of surgical site infection (SSI).
      Differences in the depth and timing of hypothermia and the surgical procedure may
      have led to conflicting results. METHODS: Patients undergoing gastroenterologic
      surgery with a duration of >3 h were analyzed. Hypothermia was defined as a core
      temperature <36 degrees C and was classified as mild (35.5-35.9 degrees C),
      moderate (35.0-35.4 degrees C), or severe (<35.0 degrees C). Hypothermia also was
      classified as early-nadir (<36 degrees C within two h of anesthesia induction)
      and late-nadir (after that time). Risk factors for SSIs were analyzed according
      to these classifications. RESULTS: Among 1,409 patients, 528 (37.5%) had
      hypothermia, which was classified as mild in 358, moderate in 137, and severe in
      33. Early-nadir and late-nadir hypothermia was found in 23.7% and 13.8%,
      respectively. There was no significant difference in the incidence of SSIs
      between patients with and without hypothermia (relative risk 1.00; 95% confidence
      interval [CI] 0.80-1.25; p = 0.997). However, there was a significantly greater
      incidence of SSIs in patients with severe hypothermia (33.3%) than in those with
      normothermia (19.2%; p = 0.045) or mild hypothermia (17.0%; p = 0.021). The
      incidence of SSIs also was significantly greater in patients with late-nadir than
      in those with early-nadir hypothermia (23.7% vs. 16.5%; p = 0.041). The incidence
      of organ/space SSIs was significantly greater in patients with late-nadir
      hypothermia (19.6%) than in patients with normothermia (12.7%; p = 0.012). In
      multivariable analysis, neither severe hypothermia (odds ratio 1.24; 95% CI 0.56
      2.77] nor late-nadir hypothermia (OR 0.71; 95% CI 0.46-1.01) was an independent
      risk factor for SSIs. CONCLUSIONS: Severe and late-nadir hypothermia were
      associated with a greater incidence of SSIs and organ/space SSIs. However,
      neither of these patterns was identified as an independent risk factor for SSIs,
      possibly because of the small number of patients.

PMID- 27027207
TI  - [Oculocardiac reflex associated with orbital floor fracture; the value of a
      reliable patient history].
AB  - BACKGROUND: The oculocardiac reflex presents when traction is applied to ocular
      muscles or on compression of the eyeball in the orbit. It is a vasovagal reaction
      that may be accompanied by bradycardia, nausea and vomiting. CASE DESCRIPTION: A
      6-year-old boy presented with vomiting and acute pain in his right eye, but no
      history of trauma. On physical examination we found no abnormalities other than
      bradycardia. Ocular examination showed an elevation restriction and slight
      depression restriction as well as ptosis of the affected eye. A cerebral MRI scan
      showed a blow-out fracture of the orbital floor with herniation of the inferior
      rectus muscle. The oculocardiac reflex explained the bradycardia and vomiting.
      Later, the boy told us that he had in fact hit his eye with his own knee.
      CONCLUSION: When patients present with acute pain in the eye and vasovagal
      symptoms, the oculocardiac reflex that can accompany a fracture of the orbital
      floor should be considered. The early recognition and treatment of this fracture
      are necessary to prevent permanent motility restrictions of the eye. A patient's
      history is not always reliable and should not limit a differential diagnosis.

PMID- 27027206
TI  - Sweet Eating Habit: Does This Affect the Results After Sleeve Gastrectomy?
AB  - BACKGROUND: It is commonly believed that eating habits, specially the sweet
      eating habit, can predict results after bariatric surgery; for this reason, it is
      considered one of the selection criteria when deciding the surgical technique.
      However, there is not enough evidence of its impact on the results after sleeve
      gastrectomy (SG). OBJECTIVE: To evaluate the relationship between the sweet
      eating habit and weight loss after SG. DESIGN: Cross-sectional retrospective
      study. MATERIAL AND METHODS: Group A: nonobese subjects, and group B: patients
      who underwent SG and had >=6 months follow-up. Demographics, anthropometrics,
      percentage excess weight loss (%EWL) at 6, 12, and 24 months, and eating habits
      before surgery were analyzed. Sweet eating consumption was classified as follows:
      mild, moderate, and severe. Uni- and bivariate logistic regression analysis
      according to each variable was performed. RESULTS: Between 2006 and 2011, 157
      patients underwent SG at our institution; 36% were male, age 41 years old, and
      initial body mass index 46 kg/m(2). Mean %EWL at 6, 12, and 24 months was 66%,
      77%, and 70%, respectively. Sweet eating consumption: Mild: 59%; Moderate: 38%;
      and Severe: 3%. No difference was found in sweet eating patterns among groups A
      and B; %EWL for mild, moderate, and severe sweet eaters at 6 months was 66 +/-
      16, 66 +/- 14, and 65 +/- 10, respectively (P = non-significant [NS]). The same
      analysis was made at 12 months: 76 +/- 20, 79 +/- 18, and 78 +/- 11 (P = NS). At
      24 months, only mild and moderate sweet eaters were available for comparison: 69
      +/- 23 and 73 +/- 19, respectively (P = NS). CONCLUSION: Preliminary data
      suggested that preoperative sweet eating habit would not predict results after SG
      in terms of weight loss.

PMID- 27027208
TI  - [Re-use of medical data for research. What do the Dutch think of the requirement
      for explicit consent?].
AB  - OBJECTIVE: How do healthcare consumers perceive the use of medical data for
      scientific research, within the framework of protection of their personal data?
      DESIGN: Survey among 731 members of the Healthcare Consumer Panel of the
      Netherlands Institute for Health Services Research (NIVEL). METHOD: A written and
      online questionnaire was used, consisting of general questions and 4 cases per
      respondent. The questions concerned the degree of trust respondents have in the
      use of previously registered data for different kinds of healthcare research, and
      their willingness to make data available under various conditions without being
      asked for explicit consent. RESULTS: Respondents showed a high degree of trust in
      scientific researchers and physicians concerning the re-use of medical data for
      research. A majority agreed that it is not necessary to be explicitly asked for
      consent for this kind of research, providing they are informed: one-third found
      their autonomy in being able to decide to be more important than scientific
      progress; three-quarters found explicit permission unnecessary as long as the
      data is well-protected and only used for scientific research. CONCLUSION: Data
      protection in research should be proportional to the risks of misuse and the
      benefits of the use of the data for research. A large majority of healthcare
      users trust the researchers, and the existing codes of conduct protect data
      sufficiently. Therefore, we see no need for stricter requirements for the use of
      health data, which would unnecessarily limit healthcare research. We do consider
      greater transparency about the research process to be necessary, in order to
      maintain a proper balance between personal-data protection and the need to
      emphasise the necessity for learning in the healthcare system.

PMID- 27027209
TI  - [Incidence of neuralgic amyotrophy in a primary care setting: a prospective
      cohort study].
AB  - OBJECTIVE: To assess the incidence of classic neuralgic amyotrophy (NA) in a
      primary care setting. DESIGN: Prospective cohort study. METHOD: During the year
      2012 we registered all new cases of neck, shoulder or arm symptoms from two large
      primary care centres serving a population of 14,118. Prior to commencing the
      study, general practitioners attended a short training session on how to diagnose
      classic NA. After inclusion, patients in whom general practitioners suspected NA
      were offered a neurologic assessment for diagnostic confirmation. RESULTS: Of the
      492 patients identified with new onset of neck, shoulder or arm symptoms, 34 were
      suspected of having NA. Neurologic evaluation confirmed the diagnosis in 14
      patients. For the Netherlands, this translates to an incidence of 1 in 1,000.
      CONCLUSION: Our findings suggest that NA is 30-50 times more common than
      previously thought; in the Netherlands, this would mean 17,000 instead of 500 new
      cases each year. Lack of awareness of the disorder and its clinical presentation
      seems the most likely explanation for this difference. Since NA may lead to
      sustained symptoms and functional limitations in the chronic phase, increased
      attention is urgently required to improve diagnostics and treatment.

PMID- 27027210
TI  - Promoting resiliency for interprofessional faculty and senior medical students:
      Outcomes of a workshop using mind-body medicine and interactive reflective
      writing.
AB  - BACKGROUND: Health care professions faculty/practitioners/students are at risk
      for stress and burnout, impacting well-being, and optimal patient care. AIMS: We
      conducted a unique intervention: an interprofessional, experiential, skills-based
      workshop (IESW) combining two approaches: mind-body medicine skills and
      interactive reflective writing (RW) fostering self-awareness, self-discovery,
      reflection, and meaning-making, potentially preventing/attenuating burnout and
      promoting resiliency. METHODS: Medical and nursing faculty and senior medical
      students (N = 16) participated in a 2-hour workshop and completed (1)
      Professional Quality of Life measure (ProQOL) and (2) a questionnaire evaluating
      understanding of professional burnout and resiliency and perceived being prepared
      to apply workshop techniques. Thematic analyses of anonymized RWs exploring
      meaningful clinical or teaching experiences were conducted. RESULTS: Participants
      reported better understanding of professional burnout/resiliency and felt better
      prepared to use meditation and RW as coping tools. RW themes identified
      experiencing/grappling with a spectrum of emotions (positive and negative) as
      well as challenge and triumph within clinical and teaching experiences as
      professionally meaningful. CONCLUSIONS: Positive outcomes were obtained within a
      synergistic resiliency skills building exercise. Successful implementation of
      this IESW provides good rationale for studying impact of this intervention over a
      longer period of time, especially in populations with high rates of stress and
      burnout.

PMID- 27027211
TI  - Optimizing Patient Surgical Management Using WhatsApp Application in the Italian
      Healthcare System.
AB  - INTRODUCTION: Smartphones changed the method by which doctors communicate with
      each other, offer modern functionalities sensitive to the context of use, and can
      represent a valuable ally in the healthcare system. Studies have shown that
      WhatsAppTM application can facilitate communication within the healthcare team
      and provide the attending physician a constant oversight of activities performed
      by junior team members. The aim of the study was to use WhatsApp between two
      distant surgical teams involved in a program of elective surgery to verify if it
      facilitates communication, enhances learning, and improves patient care
      preserving their privacy. METHODS: We conducted a focused group of surgeons over
      a 28-month period (from March 2013 to July 2015), and from September 2014 to July
      2015, a group of selected specialists communicated healthcare matters through the
      newly founded "WhatsApp Surgery Group." Each patient enrolled in the study signed
      a consent form to let the team communicate his/her clinical data using WhatsApp.
      Communication between team members, response times, and types of messages were
      evaluated. RESULTS: Forty six (n = 46) patients were enrolled in the study. A
      total of 1,053 images were used with an average of 78 images for each patient
      (range 41-143). 125 h of communication were recorded, generating 354
      communication events. The expert surgeon had received the highest number of
      questions (P, 0.001), while the residents asked clinical questions (P, 0.001) and
      were the fastest responders to communications (P, 0.001). CONCLUSION: Our study
      investigated how two distant clinical teams may exploit such a communication
      system and quantifies both the direction and type of communication between
      surgeons. WhatsApp is a low cost, secure, and fast technology and it offers the
      opportunity to facilitate clinical and nonclinical communications, enhance
      learning, and improve patient care preserving their privacy.

PMID- 27027212
TI  - Conflict of interest in EOH research.

PMID- 27027214
TI  - [Children of mentally ill parents - support needs and management status of
      families].

PMID- 27027215
TI  - [Subjective Needs of Support in Families with a Mentally Ill Parent - A
      Literature Review].
AB  - Mentally ill parents are often sceptical about professional help for their
      children although these children face an increased risk to develop a mental
      disease themselves. To get a better understanding of needs and help-seeking
      behaviour in those families a systematic literature review was conducted. Four
      databases (FIS, PsycINFO, PSYNDEX, PubPsych) were scanned for international and
      national research literature. Out of 18,057 articles 56 were included which
      report quantitative or qualitative studies taking the children's and parents'
      perspectives into account. A thematic synthesis was done to categorize the needs.
      Results concerning the help-seeking behaviour and the influence of demographic
      variables were extracted and summarized. Our results were limited by the aspect
      that no evaluation of study quality had been made and influences on the
      categorizing process by the authors' subjective perceptions are likely. There
      were a lot of hints regarding the needs of the families, but little report was
      found about help-seeking behaviour and demographic variables. The "health
      literacy" concept was discussed as a basis for further research in this area.

PMID- 27027216
TI  - [Families Affected by Parental Illness - What Obstacles Prevent them from
      Claiming Help and how Could their Supply Situation be Improved?].
AB  - Families Affected by Parental Illness - What Obstacles Prevent them from Claiming
      Help and how Could their Supply Situation be Improved? Current studies describe
      families affected by parental mental illness as a high-risk group. Although,
      interventions and programs were developed, the supply situation is still
      insufficient. In terms of a triangulation method, the present qualitative
      research with problem-centered semi-structured interviews stands in addition to
      the results of a quantitative study. This research investigates, which factors
      influence the claim of help and how the supply situation could be improved. 14
      mothers and fathers in inpatient psychiatric treatment were interviewed. For
      instance is there a small awareness level of low-threshold services, parents also
      talk about different fears towards helpers or financial difficulty which prevent
      them from seeking help. 

PMID- 27027217
TI  - [Do Attachment Styles of Mentally Ill Parents Impact on the Health-related
      Quality of Life of their Children?].
AB  - Do Attachment Styles of Mentally Ill Parents Impact on the Health-related Quality
      of Life of their Children? Parents with a mental disorder often display a
      problematic attachment style which may impact on their children's health related
      quality of life (HrQoL). The current study cross-sectionally examines attachment
      styles (BEPE) in mentally ill parents with underage children (n = 62) and the
      effect of attachment on their children's HrQoL (KINDL-R). Results show that
      secure attachment is less represented in parents with a mental health condition
      than in a healthy reference group. Within the clinical sample, children of
      mentally ill parents with a secure attachment style exhibit a higher HrQoL than
      children of mentally ill parents with ambivalent or avoidant attachment styles.
      These findings indicate not only that problematic attachment styles frequently
      occur in families with a mentally ill parent, but also suggest that this
      negatively affects the children's HrQoL. Appropriate interventions should include
      attachment oriented concepts. 

PMID- 27027218
TI  - [Comorbid Personality Disorders and Parenting Stress in Mothers with Postpartum
      Depression].
AB  - The original peer-reviewed paper presents the results of the analysis of the
      effects of psychiatric comorbidities of maternal postpartum depression, anxiety
      disorder and personality disorder (PD) on parenting stress. In the aforementioned
      analysis, mothers without PD (depression/ anxiety only) were compared to mothers
      with Borderline PD and mothers with other PD. Depending on the maternal PD,
      different sources of parenting stress have been revealed as specific to the
      mothers' experience of parenting stress, suggesting differential indications for
      psychosocial interventions to ease the burden of stress on the mother-infant
      system.

PMID- 27027222
TI  - Trends in blood pressure control and medication use during 20 years in a
      hypertension clinic in Japan.
AB  - Guidelines for the management of hypertension have recommended strict control of
      blood pressure to help prevent cardiovascular disease. The aim of the present
      study was to evaluate the current status of blood pressure control and trends
      over the past two decades. Four hundred patients treated for hypertension at
      Kyushu University Hospital were included in the present study. Blood pressure
      levels and prescribed antihypertensive drugs were examined in 2011. The average
      blood pressure was 129/74 mmHg, and the number of prescribed antihypertensive
      drugs was 2.2. Angiotensin II receptor antagonists, angiotensin-converting enzyme
      inhibitors, calcium channel blockers, diuretics, alpha-blockers, and beta
      blockers were prescribed in 66%, 5%, 78%, 21%, 12%, and 27% of the cases,
      respectively. Systolic blood pressure was significantly higher, and diastolic
      blood pressure was significantly lower in patients aged 80 years or older
      compared with the younger patients (<80 and >=80 years, 128/75 mmHg and 133/68
      mmHg, respectively). The number of prescribed antihypertensive drugs was similar
      between the two groups. Sixty-five patients were continuously treated for 20
      years. The average blood pressure of these patients significantly decreased from
      142/87 mmHg in 1991 to 128/71 mmHg in 2011, accompanied with an increase in the
      number of antihypertensive drugs from 1.6 in 1991 to 2.7 in 2011. These findings
      suggest that the revised guidelines for the management of hypertension may have
      contributed to increased awareness and better management of blood pressure
      levels. 

PMID- 27027223
TI  - Development of an ELISA for High-Throughput Screening of Inhibitors of Cdk5
      Mediated PPARgamma Phosphorylation.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is the target
      for the thiazolidinedione class of potent insulin-sensitizing drugs, which
      includes rosiglitazone and pioglitazone. However, their usage has been restricted
      due to severe side effects. Recent data have shown that specifically inhibiting
      the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of PPARgamma at
      Ser273 may lead to novel insulin sensitizers with fewer side effects. Here we
      describe a novel enzyme-linked immunosorbent assay (ELISA) in the 384-well
      format, which enables screening for PPARgamma ligands that inhibit
      phosphorylation at Ser273 by Cdk5. The assay is robust with a Z-factor  > 0.6,
      demonstrating its suitability for high-throughput screening. We demonstrate the
      suitability of this assay for profiling of published PPARgamma ligands and
      identification of novel compounds that prevent the Cdk5-mediated phosphorylation
      of PPARgamma at Ser273 in a 622 compound pilot study. Our assay enables the
      discovery and development of novel therapeutic agents for use in type-2 diabetes.
      Furthermore, our results in combination with structural analysis of reported
      PPARgamma ligand binding domain X-ray structures give a molecular rationale for
      the Cdk5-mediated phosphorylation of PPARgamma at Ser273.

PMID- 27027224
TI  - Redox flexibility of iron complexes supported by sulfur-based tris(o
      methylenethiophenolato)amine relative to its tripodal oxygen-based congener.
AB  - Tripodal ligands designed to generate a local C3 symmetry have resulted in novel
      types of metal complexes that feature unusual bonding and electronic properties.
      However, most complexes reported to date are characterised by strong field
      ligands that enforce low or intermediate-spin states for the metal centres.
      Moreover, anionic sulfur-based tripodal ligands are particularly scarce due to
      their challenging synthesis. In this context, we herein report the synthesis,
      spectral characterization, structural, and electronic properties of an iron
      complex supported by the tripodal, trianionic ligand [N(CH2ArS)3](3-) as the
      trigonal-bipyramidal complexes [Fe{N(CH2ArS)3}(X)] ((X), X = DMSO, THF). The
      solid-state structures reveal local C3v symmetry around the Fe(3+) ions, while
      electron spin resonance measurements established a high-spin state (S = 5/2).
      Electrochemical studies demonstrate the redox flexibility of the FeS3 fragment by
      direct comparison with the oxygen-based analogue N(CH2ArOH)3, which displays an
      irreversible reduction; in contrast, (THF) has a reversible Fe(3+)/Fe(2+) redox
      process at -0.83 V (relative to the ferrocenium/ferrocene redox couple). The high
      spin and redox properties of (THF) are attributable to the weak ligand field
      provided by the NS3 fragment, as confirmed by the electronic structure calculated
      by density functional theory, which reveals substantial electronic delocalisation
      and covalency of the Fe-S bonds in (X). 

PMID- 27027225
TI  - Some computer graphical user interfaces in radiation therapy.
AB  - In this review, five graphical user interfaces (GUIs) used in radiation therapy
      practices and researches are introduced. They are: (1) the treatment time
      calculator, superficial X-ray treatment time calculator (SUPCALC) used in the
      superficial X-ray radiation therapy; (2) the monitor unit calculator, electron
      monitor unit calculator (EMUC) used in the electron radiation therapy; (3) the
      multileaf collimator machine file creator, sliding window intensity modulated
      radiotherapy (SWIMRT) used in generating fluence map for research and quality
      assurance in intensity modulated radiation therapy; (4) the treatment planning
      system, DOSCTP used in the calculation of 3D dose distribution using Monte Carlo
      simulation; and (5) the monitor unit calculator, photon beam monitor unit
      calculator (PMUC) used in photon beam radiation therapy. One common issue of
      these GUIs is that all user-friendly interfaces are linked to complex formulas
      and algorithms based on various theories, which do not have to be understood and
      noted by the user. In that case, user only needs to input the required
      information with help from graphical elements in order to produce desired
      results. SUPCALC is a superficial radiation treatment time calculator using the
      GUI technique to provide a convenient way for radiation therapist to calculate
      the treatment time, and keep a record for the skin cancer patient. EMUC is an
      electron monitor unit calculator for electron radiation therapy. Instead of doing
      hand calculation according to pre-determined dosimetric tables, clinical user
      needs only to input the required drawing of electron field in computer graphical
      file format, prescription dose, and beam parameters to EMUC to calculate the
      required monitor unit for the electron beam treatment. EMUC is based on a semi
      experimental theory of sector-integration algorithm. SWIMRT is a multileaf
      collimator machine file creator to generate a fluence map produced by a medical
      linear accelerator. This machine file controls the multileaf collimator to
      deliver intensity modulated beams for a specific fluence map used in quality
      assurance or research. DOSCTP is a treatment planning system using the computed
      tomography images. Radiation beams (photon or electron) with different energies
      and field sizes produced by a linear accelerator can be placed in different
      positions to irradiate the tumour in the patient. DOSCTP is linked to a Monte
      Carlo simulation engine using the EGSnrc-based code, so that 3D dose distribution
      can be determined accurately for radiation therapy. Moreover, DOSCTP can be used
      for treatment planning of patient or small animal. PMUC is a GUI for calculation
      of the monitor unit based on the prescription dose of patient in photon beam
      radiation therapy. The calculation is based on dose corrections in changes of
      photon beam energy, treatment depth, field size, jaw position, beam axis,
      treatment distance and beam modifiers. All GUIs mentioned in this review were
      written either by the Microsoft Visual Basic.net or a MATLAB GUI development tool
      called GUIDE. In addition, all GUIs were verified and tested using measurements
      to ensure their accuracies were up to clinical acceptable levels for
      implementations. 

PMID- 27027226
TI  - Modified Canaloplasty: A New, Effective, and Safe Option for Glaucoma Patients
      With a Disrupted Schlemm Canal Wall.
AB  - PURPOSE: We describe a modified canaloplasty technique and report the short-term
      efficacy for primary open-angle glaucoma (POAG) patients with disruption of
      Schlemm canal (SC) wall resulting from prior glaucoma surgery. PATIENTS AND
      METHODS: This was a single-surgeon prospective cohort study. POAG patients
      scheduled for canaloplasty were included and divided into 2 groups: group1
      included POAG patients without a history of glaucoma surgery and group 2 included
      POAG patients with failed glaucoma surgery and disrupted SC. The status of SC was
      determined by gonioscopy and ultrasound biomicroscopy. Standard canaloplasty
      procedures were performed in group 1. A modified canaloplasty technique was used
      in group 2. Primary outcome measures included the intraocular pressure and
      glaucoma medication use at various follow-up points. RESULTS: Seventeen patients
      were enrolled in group 1 and 9 patients were enrolled in group 2. At the 12-month
      follow-up, there was no significant difference between groups 1 and 2 (17.8+/-2.7
      vs. 16.7+/-2.4 mm Hg, respectively; P=0.362) and in the mean number of
      medications (0.9+/-1.2 vs. 0.3+/-0.5, respectively; P=0.061). In both groups, at
      all follow-up points, the intraocular pressure and the mean glaucoma medication
      usage had decreased significantly compared with measurements at baseline
      (P<0.001). The rate for successful circumferential catheterization was not
      significant between the 2 groups (88.2% vs. 77.8%, P=0.063). CONCLUSION: Modified
      canaloplasty is a feasible, safe, and potentially effective option for patients
      with POAG and regions of SC disruption resulting from previous glaucoma-filtering
      surgery.

PMID- 27027227
TI  - Medium-term Outcomes of Unsutured Scleral Flap Trabeculectomies.
AB  - PURPOSE: To examine the clinical characteristics and medium-term outcomes of
      unsutured scleral flap trabeculectomies. PATIENT AND METHODS: A retrospective
      review of 45 patients who underwent 50 unsutured scleral flap trabeculectomies by
      a single ophthalmic surgeon. Information pertaining to each patient's demographic
      details, preoperative assessment, surgical procedure, and 2 years of
      postoperative management were obtained. RESULTS: The average age of patients was
      72.4+/-12.5 (range, 30 to 97) years. The diagnosis was primary open-angle
      glaucoma in 38 (76.0%) cases. The average preoperative, 1 year postoperative and
      2-year postoperative intraocular pressure (with number of topical antiglaucoma
      medications) were 20.8 (2.5), 13.2 (0.4), and 12.6 mm Hg (0.7), respectively. The
      procedure performed was a trabeculectomy alone in 32 (64.0%) cases, and combined
      trabeculectomy and phacoemulsification in 18 (36.0%) cases. Four were performed
      with mitomycin C. Three procedures (6%) had intraoperative complications (2 iris
      prolapses, 1 subconjunctival hemorrhage). Seven procedures were complicated by a
      postoperative choroidal detachment, which were managed conservatively and
      resolved spontaneously over time. There was 1 case (2%) of postoperative
      hypotony, which failed to resolve (intraocular pressure of <6 mm Hg for >3
      months). CONCLUSIONS: The majority of unsutured scleral flap trabeculectomies had
      an acceptable risk profile and resulted in a decrease in the intraocular pressure
      at 2 years postoperatively.

PMID- 27027228
TI  - IOP Elevation After Cataract Surgery: Results for Residents and Senior Staff at
      Henry Ford Health System.
AB  - PURPOSE: To determine the incidence of intraocular pressure (IOP) elevation on
      postoperative day 1 (POD1) after cataract surgery performed by resident surgeons
      compared with attending surgeons and to examine the influence of associated
      variables on the incidence of postoperative IOP elevation. PATIENTS AND METHODS:
      Retrospective review of 2472 consecutive 2.2 to 2.8 mm temporal clear corneal
      cataract extractions by phacoemulsification performed by either residents or
      attending surgeons at Henry Ford Health System. Fellow eyes were excluded,
      resulting in 1847 eyes. IOP measurements of >40, >30, and >23 mm Hg were noted
      along with incremental IOP elevations of >=10 and 20 mm Hg over
      preoperative/baseline IOP. Associated variables included: age, sex, diabetes
      mellitus, hypertension, glaucoma, glaucoma suspect, uveitis, prior ocular trauma,
      and vitreous loss at surgery. RESULTS: Resident-performed cataract surgery was
      associated with statistically significant higher rates of IOP elevation in all
      categories and in all clinical situations known to be associated with
      postoperative IOP spike, that is, vitreous loss at surgery, prior ocular trauma,
      and preexisting glaucoma. CONCLUSIONS: The incidence of postoperative day 1 IOP
      elevation after phacoemulsification performed by resident surgeons was 2 to 5
      times that of experienced cataract surgeons. Variables including vitreous loss at
      surgery, prior ocular trauma, preexisting glaucoma, glaucoma suspect status, and
      male sex were significant contributors. Consideration for prophylactic IOP
      lowering is advised in high-risk patients.

PMID- 27027229
TI  - Risk Factors and the Incidence of Ocular Hypertension After Penetrating
      Keratoplasty.

PMID- 27027230
TI  - Trabeculectomy Augmented With Cyclodialysis: A Surgical Option for Refractory
      Glaucomas.

PMID- 27027231
TI  - Glaucoma Surgery Outcome in Rwanda.
AB  - PURPOSE: To assess long-term intraocular pressure (IOP) outcome after adult
      trabeculectomy surgery in Central Africa. PATIENTS AND METHODS: All adult
      glaucoma patients who underwent trabeculectomy surgery in the Kabgayi Eye Unit,
      Rwanda between August 2003 and March 2008 were invited for a follow-up visit.
      Surgical and clinical data were collected from medical records. At the study
      visit, best-corrected visual acuity was measured and Goldmann applanation
      tonometry and biomicroscopy were done. Good IOP outcome was defined as both an
      IOP<21 mm Hg and achieving >=30% reduction from the preoperative IOP. Considering
      first operated eyes, univariate and multivariate logistic regression was used to
      investigate risk factors for failure. RESULTS: Of 163 individuals operated 3 had
      died, 118 (74%) participated. Preoperatively, the mean IOP was 31 mm Hg (SD=11;
      range, 12 to 60). At the time of the follow-up study visit the mean postoperative
      IOP was 13 mm Hg (SD=5; range, 4 to 35). Good IOP outcome was achieved in 132
      eyes (84%). Univariate analysis suggested a protective effect against failure of
      use of antimetabolites [odds ratio (OR)=0.39; 95% confidence interval (CI), 0.14
      1.11; P=0.07] and a decrease in success with length of follow-up (OR=3.57; 95%
      CI, 1.09-12.50; P=0.03). The latter remained borderline significant with
      multivariate analysis. Seven eyes went from previously better vision (at least
      hand movements) down to perception of light or no perception of light after
      trabeculectomy. Particularly a flat anterior chamber in the first postoperative
      week (OR=0.07; 95% CI, 0.01-0.49; P<0.001) and late hypotony (OR=0.04; 95% CI,
      0.002-0.99; P=0.004) were significant risk factors for severe visual loss.
      CONCLUSIONS: Trabeculectomy with antimetabolites is one of the best available
      options for glaucoma management in Africa. However, the IOP control reduced at a
      follow-up duration beyond 2 years, highlighting the importance of regular long
      term follow-up.

PMID- 27027232
TI  - Robust and Biocompatible Hybrid Matrix with Controllable Permeability for
      Microalgae Encapsulation.
AB  - Hybrid beads with entrapped microalgae Chlamydomonas reinhardtii were synthesized
      for the sustainable production of high value metabolites via photosynthesis.
      Encapsulating the microalgae requires an exquisite control of material
      properties, which has been achieved by modifying the composition (alginate,
      polycation, and silica). A coating of PDADMAC precluded cell leakage as indicated
      by the OD750 value of the culture medium, and the homogeneous distribution of
      silica prevented bead shrinkage from the strong electronic force of PDADMAC,
      resulting in a robust and biocompatible matrix for the cells. Besides fabricating
      suitable porous beads for the diffusion of expected metabolites, the permeability
      can be controlled to a certain degree by applying different molecular weights of
      PDADMAC. The hybrid alginate+silica/CaCl2+PDADMAC beads possessed sufficient
      mechanical rigidity to sheer force under constant stirring and good chemical
      stability to chelating agents such as sodium citrate. Moreover, the encapsulated
      cells exhibited excellent long-term viability and cellular functionality, which
      retained about 81.5% of the original value after a 120 day encapsulation as
      observed by microscopy and oximetry measurement. This study is not only
      significant for understanding the critical role of polycations and silica
      involved in the synthesis of hybrid beads but also important for real-scale
      bioengineering applications. 

PMID- 27027233
TI  - Circulating MicroRNAs as Potential Biomarkers for Traumatic Brain Injury-Induced
      Hypopituitarism.
AB  - Traumatic brain injury (TBI), a worldwide public health problem, has recently
      been recognized as a common cause of pituitary dysfunction. Circulating microRNAs
      (miRNAs) present in the sera are characteristically altered in many pathological
      conditions and have been used as diagnostic markers for specific diseases. It is
      with this goal that we planned to study miRNA expression in patients with TBI
      induced hypopituitarism. Thirty-eight patients (27 male, 11 female; mean age, 43
      +/- 18 years) who had been admitted to the neurosurgery intensive care unit due
      to TBI were included in the acute phase of the study. In the chronic phase, miRNA
      expression profile blood samples were drawn from 25 patients who had suffered TBI
      5 years ago. In the acute phase (on Days 1, 7, and 28), a substantial amount of
      patients (26%, 40%, and 53%; respectively) had hypopituitarism (acute
      adrenocorticotropic hormone deficiency). In the chronic phase eight of 25
      patients (32%) had TBI-induced-hypopituitarism. Forty-seven age-gender-similar
      healthy controls (25 male, 22 female, mean age: 41 +/- 14 years) were included in
      the study. In order to identify potential candidate miRNA/miRNAs whose levels had
      been altered in response to TBI-induced hypopituitarism, 740 miRNA expression
      analyses were performed in the sera of TBI patients by high throughput real-time
      polymerase chain reaction. Statistical analyses showed that miRNA-126-3p (miR-126
      3p) and miRNA-3610 (miR-3610) were detected in the sera of patients who developed
      hypopituitarism on the 1st, 7th, and 28th days, and in the 5th year following
      TBI. In addition, miRNA-3907 showed statistically significant and constant
      dynamic changes on the 1st, 7th, and 28th days, and in the 5th year in the
      patients with TBI. Our results indicated that altered expression of miR-126-3p
      and miR-3610 may play an important role in the development of TBI-induced
      hypopituitarism.

PMID- 27027234
TI  - Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin
      D Exert an Anti-Inflammatory Hepatoprotective Effect.
AB  - Vitamin D has been known for its anti-inflammatory properties. Extracts derived
      from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory
      effect. These extracts contain high levels of ergosterol, which converts into
      ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by
      absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D].
      To determine the anti-inflammatory effect of overexpression of vitamin D in
      edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze
      dried, followed by measurement of vitamin D2 contents, in their dry weight.
      C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom
      extract prior and during concanavalin A-immune-mediated liver injury. Exposure to
      ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms.
      Following feeding of vitamin D-enriched mushroom extracts to mice with immune
      mediated hepatitis, a significant decrease in liver damage was noted. This was
      shown by a decrease in alanine aminotransferase and aspartate aminotransferase
      serum levels, a decrease in proportion of mice with severe liver injury, and by
      improvement in liver histology. These effects were associated with a decrease in
      serum interferon gamma levels. A synergistic effect was noted between the anti
      inflammatory effect of the mushroom extracts and that of vitamin D. Oral
      administration of vitamin D-enriched L. edodes edible mushroom exerts a
      synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data
      support its potential use as safe immunomodulatory adjuvant for the treatment of
      HCV and nonalcoholic steatohepatitis. 

PMID- 27027236
TI  - Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of
      cancer cells in a cell-specific metabolism-dependent manner.
AB  - 2-Oxoglutarate dehydrogenase (OGDH) of the tricarboxylic acid (TCA) cycle is
      often implied to be inactive in cancer, but this was not experimentally tested.
      We addressed the question through specific inhibition of OGDH by succinyl
      phosphonate (SP). SP action on different cancer cells was investigated using
      indicators of cellular viability and reactive oxygen species (ROS), metabolic
      profiling and transcriptomics. Relative sensitivity of various cancer cells to SP
      changed with increasing SP exposure and could differ in the ATP- and NAD(P)H
      based assays. Glioblastoma responses to SP revealed metabolic sub-types
      increasing or decreasing cellular ATP/NAD(P)H ratio under OGDH inhibition. Cancer
      cell homeostasis was perturbed also when viability indicators were SP-resistant,
      e.g. in U87 and N2A cells. The transcriptomics database analysis showed that the
      SP-sensitive cells, such as A549 and T98G, exhibit the lowest expression of OGDH
      compared to other TCA cycle enzymes, associated with higher expression of
      affiliated pathways utilizing 2-oxoglutarate. Metabolic profiling confirmed the
      dependence of cellular SP reactivity on cell-specific expression of the pathways.
      Thus, oxidative decarboxylation of 2-oxoglutarate is significant for the
      interdependent homeostasis of NAD(P)H, ATP, ROS and key metabolites in various
      cancer cells. Assessment of cell-specific responses to OGDH inhibition is of
      diagnostic value for anticancer strategies. 

PMID- 27027237
TI  - Resistance of ground glass hepatocytes to oral antivirals in chronic hepatitis B
      patients and implication for the development of hepatocellular carcinoma.
AB  - Ground glass hepatocytes (GGHs) have been shown to predict the development of
      hepatocellular carcinoma (HCC). Type I GGH and type II GGH harbor hepatitis B
      virus (HBV) pre-S1 and pre-S2 deletion mutants, respectively. Whether anti-HBV
      therapy can inhibit the expression of GGHs and potentially reduce HCC development
      is explored in this study. Two sets of liver specimens were included: the first
      contained 31 paired biopsy specimens obtained from chronic HBV patients receiving
      oral nucleos(t)ide analogue (NA) treatment; the second contained 186 resected
      liver tissues obtained from HBV-related HCC patients receiving surgery: 82
      received NA before surgery and 104 did not. Compared with the baseline biopsy
      specimens, type I (P=0.527) and type II GGH (P=0.077) were not significantly
      decreased after 48 weeks of NA treatment in the first set of patients. In the
      second set, despite suppression of viral load (P<0.001) and periportal necrosis
      (P=0.006) in treated patients, GGH (P=0.594), cccDNA (P=0.172) and serum pre-S
      mutants (p=0.401) were not significantly suppressed. A significant decrease of
      type I (P=0.049) and type II GGH (P=0.029) could only be observed in patients
      after long duration of treatment (median duration: 4.3 years). In the treated
      patients, the persisted type II GGH remained an independent variable associated
      with decreased local recurrence-free survival of HCC (P=0.019) as in non-treated
      patients (P=0.001). In conclusion, the persistence of GGHs could explain the
      residual risk of HCC development under anti-HBV treatment. Therefore,
      intrahepatic GGHs and pre-S mutant are potential additional targets for HCC
      prevention in patients already receiving anti-HBV treatment. 

PMID- 27027235
TI  - Multidisciplinary management of hepatocellular carcinoma with portal vein tumor
      thrombus - Eastern Hepatobiliary Surgical Hospital consensus statement.
AB  - Hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT)
      is associated with poor prognosis, early recurrence of HCC, and limited treatment
      options. Current guidelines do not have standardized diagnostic and treatment
      modalities, thus creating a need for a multidisciplinary treatment model for
      standardization of the treatment. Eastern Hepatobiliary Surgical Hospital (China)
      convened two working parties of experts from all the departments, to consolidate
      the current evidence, prevailing vision for the future, and experience of the
      practicing clinicians engaged in HCC management, so as to develop a consensus for
      PVTT diagnosis and treatment according to the GRADE system. Based on the quality
      of the existing evidence and the strength of recommendations, the consensus
      statements were categorized into 3 evidence levels (A/B/C) and 5 classes
      (I/II/IIa/IIb/III).The panel discussed and provided clarity on the management and
      research options in the field of HCC with PVTT. In addition, the panel also
      assessed the quality of the cited studies and assigned grades to the
      recommendation statements. Among the group of experts, there was excellent
      agreement with regard to effective diagnosis and treatment of HCC with PVTT. The
      recommendations of this consensus will provide guidance to physicians and
      clinical researchers on the effective management of HCC with PVTT.

PMID- 27027238
TI  - Use of dedicated gene panel sequencing using next generation sequencing to
      improve the personalized care of lung cancer.
AB  - Advances in Next Generation Sequencing (NGS) technologies have improved the
      ability to detect potentially targetable mutations. However, the integration of
      NGS into clinical management in an individualized manner remains challenging. In
      this single-center observational study, we performed a dedicated NGS panel
      studying 41 cancer-related genes in 50 consecutive patients with metastatic non
      small-cell lung cancer between May 2012 and October 2014. Molecular analysis
      could be performed in 48 patients with a good quality check. One hundred and
      thirty-three mutations, whose twenty-four unique mutations, were detected. At
      least one mutation was found in 46 patients. In 58% of cases, the Molecular Tumor
      Board (MTB) was able to recommend treatment with a targeted agent based on the
      evaluation of the tumor genetic profile and treatment history. Nine patients
      (18%) were subsequently treated with a MTB-recommended targeted therapy; four
      patients experienced a clinical benefit with a partial response or stabilization
      lasting more than 4 months. In this case series involving patients with
      metastatic non-small cell lung cancer, we show that including integrative
      clinical sequencing data into routine clinical management was feasible and could
      impact on patient therapeutic proposal. 

PMID- 27027239
TI  - Estimation of the risk of secondary malignancy arising from whole-breast
      irradiation: comparison of five radiotherapy modalities, including TomoHDA.
AB  - The risk of secondary cancer from radiation treatment remains a concern for long
      term breast cancer survivors, especially those treated with radiation at the age
      younger than 45 years. Treatment modalities optimally maximize the dose delivery
      to the tumor while minimizing radiation doses to neighboring organs, which can
      lead to secondary cancers. A new TomoTherapy treatment machine, TomoHDATM, can
      treat an entire breast with two static but intensity-modulated beams in a slice
      by-slice fashion. This feature could reduce scattered and leakage radiation
      doses. We compared the plan quality and lifetime attributable risk (LAR) of a
      second malignancy among five treatment modalities: three-dimensional conformal
      radiation therapy, field-in-field forward-planned intensity-modulated radiation
      therapy, inverse-planned intensity-modulated radiation therapy (IMRT), volumetric
      modulated arc therapy, and TomoDirect mode on the TomoHDA system. Ten breast
      cancer patients were selected for retrospective analysis. Organ equivalent doses,
      plan characteristics, and LARs were compared. Out-of-field organ doses were
      measured with radio-photoluminescence glass dosimeters. Although the IMRT plan
      provided overall better plan quality, including the lowest probability of
      pneumonitis, it caused the second highest LAR. The TomoTherapy plan provided plan
      quality comparable to the IMRT plan and posed the lowest total LAR to neighboring
      organs. Therefore, it can be a better treatment modality for younger patients who
      have a longer life expectancy. 

PMID- 27027240
TI  - Olfactory phenotypic expression unveils human aging.
AB  - The mechanism of the natural aging of olfaction and its declinein the absence of
      any overt disease conditions remains unclear. Here, we investigated this
      mechanism through measurement of one of the parameters of olfactory function, the
      absolute threshold, in a healthy population from childhood to old age. The
      absolute olfactory threshold data were collected from an Italian observational
      study with 622 participants aged 5-105 years. A subjective testing procedure of
      constant stimuli was used, which was also compared to the 'staircase' method,
      with the calculation of the reliability. The n-butanol stimulus was used as an
      ascending series of nine molar concentrations that were monitored using an
      electronic nose. The data were analyzed using nonparametric statistics because of
      the multimodal distribution. We show that the age-related variations in the
      absolute olfactory threshold are not continuous; instead, there are multiple
      olfactory phenotypes. Three distinct age-related phenotypes were defined, termed
      as 'juvenile', 'mature' and 'elder'. The frequency of these three phenotypes
      depends on age. Our data suggest that the sense of smell does not decrease
      linearly with aging. Our findings provide the basis for further understanding of
      olfactory loss as an anticipatory sign of aging and neurodegenerative processes. 

PMID- 27027241
TI  - A systematic review on in vitro 3D bone metastases models: A new horizon to
      recapitulate the native clinical scenario?
AB  - While the skeleton is not the only organ where metastasis can occur, it is one of
      the preferred sites, with a significant impact in patients' quality of life. With
      the aim of delineating the cellular and molecular mechanisms of bone metastasis,
      numerous studies have been employed to identify any contributing factors that
      trigger cancer progression. One of the major limitations of studying cancer-bone
      metastasis is the multifaceted nature of the native bone environment and the lack
      of reliable, simple, and not expensive models that strictly mimic the biological
      processes occurring in vivo allowing a correct translation of results. Currently,
      with the growing acceptance of in vitro models as effective tools for studying
      cancer biology, three-dimensional (3D) models have emerged as a compromise
      between two-dimensional cultures of isolated cancer cells and the complexity of
      human cancer xenografts in immunocompromised animal hosts. This descriptive
      systematic literature review summarizes the current status of advanced and
      alternative 3D in vitro bone metastases models. We have also reviewed the
      strategies employed by researchers to set-up these models with special reference
      to recent promising developments trying to better replicate the complexity and
      heterogeneity of a human metastasis in situ, with an outlook at their use in
      medicine. All these aspects will greatly contribute to the existing knowledge on
      bone metastases, providing a specific link to clinical scenarios and thus making
      3D in vitro bone metastasis models an attractive tool for multidisciplinary
      experts.

PMID- 27027242
TI  - The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo.
AB  - A phase 2 clinical trial investigating the efficacy and safety of AS602801, a
      newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is
      complete. We are now examining whether AS602801 acts against human cancer cells
      in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both
      serum-cultured non-stem cancer cells and cancer stem cells derived from human
      pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at
      concentrations that did not decrease the viability of normal human fibroblasts.
      AS602801 also inhibited the self-renewal and tumor-initiating capacity of cancer
      stem cells surviving AS602801 treatment. Cancer stem cells in established
      xenograft tumors were reduced by systemic administration of AS602801 at a dose
      and schedule that did not adversely affect the health of the tumor-bearing mice.
      These findings suggest AS602801 is a promising anti-cancer stem cell agent, and
      further investigation of the utility of AS602801 in the treatment of cancer seems
      warranted. 

PMID- 27027243
TI  - Effect of Knee Orthoses on Hamstring Contracture in Children With Cerebral Palsy:
      Multiple Single-Subject Study.
AB  - PURPOSE: To examine the effect of knee orthoses on extensibility of the
      hamstrings in children with spastic cerebral palsy (CP). METHODS: The short-term
      effects of knee orthoses on passive range of motion (ROM), spasticity, and gross
      motor function of the hamstrings. Ten children with spastic CP, aged 5 to 14
      years, at Gross Motor Function Classification System levels I to V, were
      followed. The orthoses were worn for a minimum of 30 minutes day, 5 days per
      week, during the intervention period of 8 weeks. RESULTS: Visual analysis using
      the Two Standard Deviation Band Method supported improvements in passive ROM for
      all 20 hamstring muscles and in 12 of 14 knee extension measurements. Analyses
      with the Wilcoxon signed rank test confirm the individual results and support a
      significant increase in hamstring muscles (P = .005) and knee extension (right: P
      =.028; left: P =.018) compared with baseline. CONCLUSIONS: In children with
      spastic CP, 8 weeks of treatment with knee orthoses can improve extensibility of
      the hamstrings.

PMID- 27027244
TI  - Relationship Between Central Hypotonia and Motor Development in Infants Attending
      a High-Risk Neonatal Neurology Clinic.
AB  - PURPOSE: To study the relationship between central hypotonia and motor
      development, and to determine the relative contribution of nuchal, truncal, and
      appendicular hypotonia domains to motor development. METHODS: Appendicular,
      nuchal, and truncal tones of high-risk infants were assessed, as was their
      psychomotor developmental index (PDI). Infants with peripheral hypotonia were
      excluded. RESULTS: We included 164 infants (mean age 9.6 +/- 4 months), 36 with
      normal tone in all 3 domains and 128 with central hypotonia. Twenty-six of the
      latter had hypotonia in 1 domain and 102 had multiple combinations of 3 domains.
      Hypotonia domains were distributed as follows: truncal (n = 115), appendicular (n
      = 93), and nuchal (n = 70). Each domain was significantly associated with PDI
      scores (P < .001) but not with a later diagnosis of cerebral palsy. On linear
      regression, nuchal hypotonia had the strongest contribution to PDI scores (beta =
      -0.6 [nuchal], -0.45 [appendicular], and -0.4 [truncal], P < .001). CONCLUSIONS:
      Central hypotonia, especially nuchal tone, is associated with lowered motor
      development scores.

PMID- 27027245
TI  - HIV-1 at the placenta: immune correlates of protection and infection.
AB  - PURPOSE OF REVIEW: Mother-to-child transmission (MTCT) of HIV-1 remains a
      significant global health concern despite implementation of maternal combination
      antiretroviral therapy for treatment as prevention to offset transmission. The
      risk of in-utero HIV-1 transmission in the absence of interventions is ~7%. This
      low rate of transmission points to innate and adaptive mechanisms to restrict
      lentiviral infection within the placenta. RECENT FINDINGS: Placental macrophages
      (Hofbauer cells) are key mediators in in-utero transmission of HIV-1. Hofbauer
      cells constitutively express elevated concentrations of regulatory cytokines,
      which inhibit HIV-1 replication in vitro, and possess intrinsic antiviral
      properties. Hofbauer cells sequester HIV-1 in intracellular compartments that can
      be accessed by HIV-1-specific antibodies and may occur in vivo to offset MTCT.
      Intriguingly, studies have reported strong associations between maternal human
      cytomegalovirus (HCMV) viremia and MTCT of HIV-1. HCMV infection at the placenta
      promotes inflammation, chronic villitis, and trophoblast damage, providing
      potential HIV-1 access into CD4CCR5 target cells. The placenta exhibits a variety
      of mechanisms to limit HIV-1 replication, yet viral-induced activation with
      maternal HCMV may override this protection to facilitate in-utero transmission of
      HIV-1. SUMMARY: Understanding immune correlates of protection or transmission at
      the placenta during on-going HIV-1 exposure may contribute to understanding HIV
      pathogenesis and the development of effective immunotherapies.

PMID- 27027246
TI  - Programmed Bacteria Death Induced by Carbon Dots with Different Surface Charge.
AB  - Based on a series of biochemical experiments for analysis and characterization,
      it is found that the uncharged C-dots have no effect on bacterial growth while
      the negatively charged and positively charged C-dots can induce bacteria
      apoptosis. For the positively charged C-dots, they can induce both bacteria
      apoptosis and bacteria death. These observations will provide new insights into
      bioapplications of carbon dots. 

PMID- 27027247
TI  - Preparation, characterization, and evaluation of genipin crosslinked
      chitosan/gelatin three-dimensional scaffolds for liver tissue engineering
      applications.
AB  - In liver tissue engineering, scaffolds with porous structure desgined to supply
      nutrient and oxygen exchange for three-dimensional (3-D) cells culture, and
      maintain liver functions. Meanwhile, genipin, as a natural crosslinker, is widely
      used to crosslink biomaterials in tissue engineering, with lower cytotoxicity and
      better biocompatibility. In present study, chitosan/gelatin 3-D scaffolds
      crosslinked by genipin, glutaraldehyde or 1-(3-dimethylaminopropyl)-3-ethyl
      carbodimide hydrochloride (EDC) were prepared and characterized by Fourier
      transform infrared (FT-IR) and scanning electron microscopy (SEM). The
      biocompatibility of chitosan/gelatin scaffolds corsslinked with different
      crosslinkers was investigated by cell viability, morphology and liver specific
      functions. The result showed that the 1% and 2% genipin crosslinked
      chitosan/gelatin scaffolds possess ideal porosity. The genipin crosslinked 3-D
      scaffolds possessed the best biocompatibility than that of the others, and
      maintained liver specific functions when HepG2 cells seeded on scaffolds. The
      cellular morphology of HepG2 cells seeded on scaffolds showed that cells could
      penetrate into the scaffolds and proliferate significantly. Therefore, genipin
      crosslinked chitosan/gelatin scaffolds could be a promising biomaterial used in
      liver tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 104A: 1863-1870, 2016.

PMID- 27027248
TI  - Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12
      Conjugates of the Anorectic Peptide PYY(3-36).
AB  - Vitamin B12 -peptide conjugates have considerable therapeutic potential through
      improved pharmacokinetic and/or pharmacodynamic properties imparted on the
      peptide upon covalent attachment to vitamin B12 (B12 ). There remains a lack of
      structural studies investigating the effects of B12 conjugation on peptide
      secondary structure. Determining the solution structure of a B12 -peptide
      conjugate or conjugates and measuring functions of the conjugate(s) at the target
      peptide receptor may offer considerable insight concerning the future design of
      fully optimized conjugates. This methodology is especially useful in tandem with
      constrained molecular dynamics (MD) studies, such that predictions may be made
      about conjugates not yet synthesized. Focusing on two B12 conjugates of the
      anorectic peptide PYY(3-36), one of which was previously demonstrated to have
      improved food intake reduction compared with PYY(3-36), we performed NMR
      structural analyses and used the information to conduct MD simulations. The study
      provides rare structural insight into vitamin B12 conjugates and validates the
      fact that B12 can be conjugated to a peptide without markedly affecting peptide
      secondary structure.

PMID- 27027249
TI  - Sex-specific mediation effect of the right fusiform face area volume on the
      association between variants in repeat length of AVPR1A RS3 and altruistic
      behavior in healthy adults.
AB  - Microsatellite variants in the arginine vasopressin receptor 1A gene (AVPR1A) RS3
      have been associated with normal social behaviors variation and autism spectrum
      disorders (ASDs) in a sex-specific manner. However, neural mechanisms underlying
      these associations remain largely unknown. We hypothesized that AVPR1A RS3
      variants affect altruistic behavior by modulating the gray matter volume (GMV) of
      specific brain regions in a sex-specific manner. We investigated 278 young
      healthy adults using the Dictator Game to assess altruistic behavior. All
      subjects were genotyped and main effect of AVPR1A RS3 repeat polymorphisms and
      interaction of genotype-by-sex on the GMV were assessed in a voxel-wise manner.
      We observed that male subjects with relatively short repeats allocated less money
      to others and exhibited a significantly smaller GMV in the right fusiform face
      area (FFA) compared with male long homozygotes. In male subjects, the GMV of the
      right FFA exhibited a significant positive correlation with altruistic behavior.
      A mixed mediation and moderation analysis further revealed both a significant
      mediation effect of the GMV of the right FFA on the association between AVPR1A
      RS3 repeat polymorphisms and allocation sums and a significant moderation effect
      of sex (only in males) on the mediation effect. Post hoc analysis showed that the
      GMV of the right FFA was significantly smaller in male subjects carrying allele
      426 than in non-426 carriers. These results suggest that the GMV of the right FFA
      may be a potential mediator whereby the genetic variants in AVPR1A RS3 affect
      altruistic behavior in healthy male subjects. Hum Brain Mapp 37:2700-2709, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27027250
TI  - Gene expression risk signatures maintain prognostic power in multiple myeloma
      despite microarray probe set translation.
AB  - INTRODUCTION: Gene expression profiling (GEP) risk models in multiple myeloma are
      based on 3'-end microarrays. We hypothesized that GEP risk signatures could
      retain prognostic power despite being translated and applied to whole-transcript
      microarray data. METHODS: We studied CD138-positive bone marrow plasma cells in a
      prospective cohort of 59 samples from newly diagnosed patients eligible for high
      dose therapy (HDT) and 67 samples from previous HDT patients with progressive
      disease. We used Affymetrix Human Gene 1.1 ST microarrays for GEP. Nine GEP risk
      signatures were translated by probe set match and applied to our data in
      multivariate Cox regression analysis for progression-free survival and overall
      survival in combination with clinical, cytogenetic and biochemical risk markers,
      including the International Staging System (ISS). RESULTS: Median follow-up was
      66 months (range 42-87). Various translated GEP risk signatures or combinations
      hereof were significantly correlated with survival: among newly diagnosed
      patients mainly in combination with cytogenetic high-risk markers and among
      relapsed patients mainly in combination with ISS stage III. CONCLUSION:
      Translated GEP risk signatures maintain significant prognostic power in HDT
      myeloma patients. We suggest probe set matching for GEP risk signature
      translation as part of the efforts towards a microarray-independent GEP risk
      standard. (ClicinalTrials.gov identifier: NCT00639054).

PMID- 27027251
TI  - Dermoscopy of accidental AgNO3 Staining: The phenomenon and mechanism appraisal.

PMID- 27027252
TI  - Orange pigmentation spots on the sole may be from a stink bug.

PMID- 27027253
TI  - Neuro-Sweet's disease.

PMID- 27027254
TI  - Development of a normothermic extracorporeal liver perfusion system toward
      improving viability and function of human extended criteria donor livers.
AB  - Donor organ shortages have led to an increased interest in finding new approaches
      to recover organs from extended criteria donors (ECD). Normothermic
      extracorporeal liver perfusion (NELP) has been proposed as a superior
      preservation method to reduce ischemia/reperfusion injury (IRI), precondition
      suboptimal grafts, and treat ECD livers so that they can be successfully used for
      transplantation. The aim of this study was to investigate the beneficial effects
      of a modified NELP circuit on discarded human livers. Seven human livers that
      were rejected for transplantation were placed on a modified NELP circuit for 8
      hours. Perfusate samples and needle core biopsies were obtained at hourly
      intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine
      (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal
      temperature, electrolytes, and pH and glucose levels in the perfusate along with
      physiological vascular flows and pressures. Functional, biochemical, and
      microscopic evaluation revealed no additional injuries to the grafts during NELP
      with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic
      injury. All livers synthesized adequate amounts of bile and coagulation factors.
      We also demonstrated a mild reduction (10%) of macroglobular steatosis with the
      use of the defatting solution. Histology demonstrated normal parenchymal
      architecture and a minimal to complete lack of IRI at the end of NELP. In
      conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered
      synthetic functions, and hepatobiliary parameters of ECD livers without
      additional injuries to the grafts. This approach has the potential to increase
      the donor pool for clinical transplantation. Liver Transplantation 22 979-993
      2016 AASLD.

PMID- 27027255
TI  - Diagnostic criteria for inclusion body myositis.
AB  - Inclusion body myositis (IBM) was first identified as a specific disorder about
      40 years ago and is now recognized to be the most frequently presenting primary
      myopathy in middle age and beyond. Initial characterization was based on the
      observation of specific pathological features distinguishing it from
      polymyositis. It was soon appreciated that there were also distinguishing
      clinical features. The earliest diagnostic criteria were heavily biased towards
      pathological features, but over time revised criteria have given increasing
      importance to certain clinical features. Until the specific cause of IBM is
      determined, and the basic pathogenetic mechanisms are better understood, there
      can be no diagnostic gold-standard against which to compare the sensitivity and
      specificity of any proposed diagnostic criteria, but such criteria are essential
      to ensure that patients entering clinical, epidemiological, genetic, pathological
      or therapeutic studies represent a homogeneous population. It is likely that any
      currently accepted diagnostic criteria will, once a gold-standard is eventually
      established, be shown to have 'missed' patients with atypical features, but that
      has to be accepted to make certain that current studies are not contaminated by
      patients who do not have IBM. In other words, in everyday clinical practice there
      will be the occasional patient who an experienced myologist strongly suspects has
      IBM, but does not meet current criteria - the criteria lack sensitivity. But if
      the criteria are so broad as to include all such atypical cases, they would be
      likely to include patients who do not in fact have IBM - they would lack
      specificity. The sensitivity and specificity of existing criteria have been
      reviewed recently, in so far as it is possible to do so, and found to have high
      specificity but variable sensitivity. 

PMID- 27027256
TI  - Evaluation of the cross-reactivity of antigens in Glupearl 19S and other
      hydrolysed wheat proteins in cosmetics.
AB  - BACKGROUND: In Japan, over 2000 users of a facial soap containing Glupearl 19S
      (GP19S), a hydrolysed wheat protein (HWP), developed immediate-type systemic
      wheat allergy (HWP-IWA), and ~70% of them developed associated contact urticaria.
      OBJECTIVES: We investigated whether HWP-IWA patients cross-react with other HWPs,
      and analysed HWP antigenic characteristics. METHODS: We used 10 types of HWP that
      are commercially available as cosmetic ingredients, and 16 subjects with HWP-IWA.
      We performed an enzyme-linked immunosorbent assay (ELISA) to evaluate the
      reactivity to each HWP, and western blotting to evaluate the characteristics of
      the antigens by using HWP-IWA patients' serum IgE antibodies. We also performed
      prick tests with the HWPs. RESULTS: The patients reacted to four other HWPs in
      addition to GP19S, according to ELISA, and this was confirmed by strong reactions
      in the prick tests to the same four types of HWP. Smears of antigens with
      molecular weights ranging from the high range to the low range were seen on
      western blotting with the four HWPs that showed strong reactions in the ELISA and
      prick tests. CONCLUSIONS: HWP-IWA patients cross-react with other HWPs. The
      antigens that they cross-reacted to had a molecular weight distribution similar
      to that of GP19S present in the HWPs.

PMID- 27027257
TI  - Gingival crevicular fluid levels of cytokines/chemokines in chronic
      periodontitis: a meta-analysis.
AB  - AIMS: To compare gingival crevicular fluid (GCF) cytokines/chemokines levels
      between periodontally healthy subjects and subjects diagnosed with chronic
      periodontitis (ChP), before and after non-surgical periodontal treatment, and to
      establish their predictive value for periodontal disease progression. METHODS:
      Studies indexed in MEDLINE and EMBASE published in English, Portuguese and
      Spanish were eligible for this review. Database searches up to December 2015, and
      manual search of the reference list from reviews and selected articles was
      performed. Only studies providing data on GCF cytokines/chemokines levels in
      subjects diagnosed with ChP and periodontally healthy controls were included.
      Cross-sectional, case series, single-arm clinical studies, randomized controlled
      trials and prospective/retrospective cohort studies were included. Meta-analyses
      were conducted for those cytokines/chemokines with at least three available
      studies. RESULTS: GCF levels of IL-1beta, IL-6, IFN-gamma and MCP-1/CCL2 were
      significantly higher in subjects diagnosed with ChP than periodontally healthy
      subjects. A significant decrease in GCF levels of IL-1beta and IL-17 was observed
      after non-surgical periodontal treatment, whereas a significant increase was
      observed for IL-4. CONCLUSION: Evidence for significant differences between
      periodontal health and ChP was observed for a few cytokines and one chemokine. No
      conclusions could be drawn with regards to increased risk of disease progression.

PMID- 27027259
TI  - Bifunctionalized Intrinsically Microporous Polyimides with Simultaneously
      Enhanced Gas Permeability and Selectivity.
AB  - Two novel intrinsically microporous copolyimides synthesized by condensation
      reaction of 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA),
      3,3,3',3'-tetramethyl-1,1'-spirobisindane-5,5'-diamino-6,6'-diol, and 3,5
      diaminobenzoic acid with diamine ratios of 80/20 (Co-80/20) and 50/50 (Co-50/50)
      are reported. Unexpectedly, the Co-80/20 not only demonstrates higher
      microporosity (300 m(2) g(-1) ) than the PIM-6FDA-OH homopolymer (190 m(2) g(-1)
      ) but also exhibits simultaneously enhanced CO2 permeability (from 119 to 171
      Barrer) and CO2 /CH4 selectivity (from 35 to 41) after thermal annealing at 250 
      degrees C. This higher permeability originates from enhanced diffusivity (D CO2 )
      and the higher selectivity results from its increased diffusion selectivity (D
      CO2 /D CH4 ). After crosslinking at 300  degrees C, the Co-80/20 exhibits an even
      higher CO2 permeability (261 Barrer) and almost unchanged CO2 /CH4 selectivity. 

PMID- 27027258
TI  - The relationship between vasculogenic mimicry and epithelial-mesenchymal
      transitions.
AB  - Vasculogenic mimicry (VM) is a vascular-like structure which can mimic the
      embryonic vascular network pattern to nourish the tumour tissue. As a unique
      perfusion way, VM is correlated with tumour progression, invasion, metastasis and
      lower 5-year survival rate. Notably, epithelial-mesenchymal transition (EMT)
      regulators and EMT-related transcription factors are highly up-regulated in VM
      forming tumour cells, which demonstrated that EMT may play a crucial role in VM
      formation. Therefore, the up-regulation of EMT-associated adhesion molecules and
      other factors can also make a contribution in VM-forming process. Depending on
      these discoveries, VM and EMT can be utilized as therapeutic target strategies
      for anticancer therapy. The purpose of this article is to explore the advance
      research in the relationship of EMT and VM and their corresponding mechanisms in
      tumorigenesis effect.

PMID- 27027260
TI  - TET2 regulates LncRNA-ANRIL expression and inhibits the growth of human gastric
      cancer cells.
AB  - Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5
      hydroxymethylcytosine in DNA. However, the role of TET enzymes in human gastric
      cancer remains unknown. Here, we show that TET2 mRNA and protein levels are
      downregulated in human gastric cancer tissues when compared with normal gastric
      mucosa. Low expression of TET2 predicts poor overall and disease-free survival.
      Furthermore, we demonstrate that TET2 inhibits the proliferation and colony
      formation of human gastric cancer cells by using loss-of-function and gain-of
      function strategies. Overexpression of TET2 induces apoptosis in human gastric
      cancer cells. The mechanism study shows that TET2 binds to the promoter region of
      the oncogenic long noncoding RNA (lncRNA-ANRIL) and regulates the expression of
      ANRIL and its downstream genes (INK4a, INK4b, and ARF). Finally, we demonstrate
      that ANRIL knockdown blocks the effects of TET2 on gastric cancer cell
      proliferation and colony formation. (c) 2016 IUBMB Life 68(5):355-364, 2016.

PMID- 27027261
TI  - Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2
      sensitivity during hypoglycaemia: a role for the carotid body.
AB  - KEY POINTS: Hypoglycaemia is counteracted by release of hormones and an increase
      in ventilation and CO2 sensitivity to restore blood glucose levels and prevent a
      fall in blood pH. The full counter-regulatory response and an appropriate
      increase in ventilation is dependent on carotid body stimulation. We show that
      the hypoglycaemia-induced increase in ventilation and CO2 sensitivity is
      abolished by preventing adrenaline release or blocking its receptors.
      Physiological levels of adrenaline mimicked the effect of hypoglycaemia on
      ventilation and CO2 sensitivity. These results suggest that adrenaline, rather
      than low glucose, is an adequate stimulus for the carotid body-mediated changes
      in ventilation and CO2 sensitivity during hypoglycaemia to prevent a serious
      acidosis in poorly controlled diabetes. ABSTRACT: Hypoglycaemia in vivo induces a
      counter-regulatory response that involves the release of hormones to restore
      blood glucose levels. Concomitantly, hypoglycaemia evokes a carotid body-mediated
      hyperpnoea that maintains arterial CO2 levels and prevents respiratory acidosis
      in the face of increased metabolism. It is unclear whether the carotid body is
      directly stimulated by low glucose or by a counter-regulatory hormone such as
      adrenaline. Minute ventilation was recorded during infusion of insulin-induced
      hypoglycaemia (8-17 mIU kg(-1)  min(-1) ) in Alfaxan-anaesthetised male Wistar
      rats. Hypoglycaemia significantly augmented minute ventilation (123 +/- 4 to 143
      +/- 7 ml min(-1) ) and CO2 sensitivity (3.3 +/- 0.3 to 4.4 +/- 0.4 ml min(-1) 
      mmHg(-1) ). These effects were abolished by either beta-adrenoreceptor blockade
      with propranolol or adrenalectomy. In this hypermetabolic, hypoglycaemic state,
      propranolol stimulated a rise in P aC O2, suggestive of a ventilation-metabolism
      mismatch. Infusion of adrenaline (1 MUg kg(-1)  min(-1) ) increased minute
      ventilation (145 +/- 4 to 173 +/- 5 ml min(-1) ) without altering P aC O2 or pH
      and enhanced ventilatory CO2 sensitivity (3.4 +/- 0.4 to 5.1 +/- 0.8 ml min(-1) 
      mmHg(-1) ). These effects were attenuated by either resection of the carotid
      sinus nerve or propranolol. Physiological concentrations of adrenaline increased
      the CO2 sensitivity of freshly dissociated carotid body type I cells in vitro.
      These findings suggest that adrenaline release can account for the ventilatory
      hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole
      body ventilatory CO2 sensitivity.

PMID- 27027262
TI  - Early skin-to-skin contact for healthy full-term infants after vaginal and
      caesarean delivery: a qualitative study on clinician perspectives.
AB  - AIMS AND OBJECTIVES: This study aims to provide insight into key factors from a
      clinician's perspective that influence uninterrupted early skin-to-skin contact
      after vaginal and caesarean delivery of healthy full-term infants. BACKGROUND:
      Early skin-to-skin contact of healthy full-term infants ideally begins
      immediately after birth and continues for the first hour or the first breastfeed
      as recommended by the Baby Friendly Hospital Initiative. However, adoption of
      early skin-to-skin contact is low in many settings and the barriers that hinder
      its universal use are not well understood. DESIGN: An exploratory qualitative
      research design using semi-structured interviews. METHODS: Eleven clinicians were
      interviewed, including five registered nurses and one medical doctor from the
      obstetrics and gynaecology unit as well as four registered nurses and one medical
      doctor from the neonatal intensive care unit. Core topics that were discussed
      included perceptions on early skin-to-skin contact and facilitating factors and
      barriers to early skin-to-skin contact after vaginal and caesarean delivery.
      Interview sessions were recorded, transcribed and analysed using a thematic
      analysis approach. A coding framework was developed from which subthemes emerged.
      The overall themes were adopted from Lee et al.'s thematic framework to
      categorise factors into institutional, familial-level and implementation factors.
      FINDINGS: Critical institutional factors included inadequate staffing and
      education of clinicians on early skin-to-skin contact. On a familial level,
      parental education and motivation were identified as important factors. Barriers
      to implementation included the absence of a clinical algorithm and unclear
      definitions for eligible mothers and infants. CONCLUSIONS: Various facilitating
      factors and barriers to early skin-to-skin contact of healthy full-term infants
      born via vaginal and caesarean delivery were identified. RELEVANCE TO CLINICAL
      PRACTICE: Addressing these factors can help to provide a better understanding of
      clinician perspectives on early skin-to-skin contact and help guide its
      implementation as standard of care for healthy full-term infants.

PMID- 27027263
TI  - Effect of a Clinical Practice Guideline for Pediatric Complicated Appendicitis.
AB  - IMPORTANCE: Complicated appendicitis is a common condition in children that
      causes substantial morbidity. Significant variation in practice exists within and
      between centers. We observed highly variable practices within our hospital and
      hypothesized that a clinical practice guideline (CPG) would standardize care and
      be associated with improved patient outcomes. OBJECTIVE: To determine whether a
      CPG for complicated appendicitis could be associated with improved clinical
      outcomes. DESIGN, SETTING, AND PARTICIPANTS: A comprehensive CPG was developed
      for all children with complicated appendicitis at Monroe Carell Jr Children's
      Hospital at Vanderbilt, a freestanding children's hospital in Nashville,
      Tennessee, and was implemented in July 2013. All patients with complicated
      appendicitis who were treated with early appendectomy during the study period
      were included in the study. Patients were divided into 2 cohorts, based on
      whether they were treated before or after CPG implementation. Clinical
      characteristics and outcomes were recorded for 30 months prior to and 16 months
      following CPG implementation. EXPOSURE: Clinical practice guideline developed for
      all children with complicated appendicitis at Monroe Carell Jr Children's
      Hospital at Vanderbilt. MAIN OUTCOMES AND MEASURES: The primary outcome measure
      was the occurrence of any adverse event such as readmission or surgical site
      infection. In addition, resource use, practice variation, and CPG adherence were
      assessed. RESULTS: Of the 313 patients included in the study, 183 were boys
      (58.5%) and 234 were white (74.8%). Complete CPG adherence occurred in 78.7% of
      cases (n = 96). The pre-CPG group included 191 patients with a mean (SD) age of
      8.8 (4.0) years, and the post-CPG group included 122 patients with a mean (SD)
      age of 8.7 (4.1) years. Compared with the pre-CPG group, patients in the post-CPG
      group were less likely to receive a peripherally inserted central catheter (2.5%,
      n = 3 vs 30.4%, n = 58; P < .001) or require a postoperative computed tomographic
      scan (13.1%, n = 16 vs 29.3%, n = 56; P = .001), and length of hospital stay was
      significantly reduced (4.6 days post-CPG vs 5.1 days pre-CPG, P < .05). Patients
      in the post-CPG group were less likely to have a surgical site infection
      (relative risk [RR], 0.41; 95% CI, 0.27-0.74) or require a second operation (RR,
      0.35; 95% CI, 0.12-1.00). In the pre-CPG group, 30.9% of patients (n = 59)
      experienced any adverse event, while 22.1% of post-CPG patients (n = 27)
      experienced any adverse event (RR, 0.72; 95% CI, 0.48-1.06). CONCLUSIONS AND
      RELEVANCE: Significant practice variation exists among surgeons in the management
      of pediatric complicated appendicitis. In our institution, a CPG that
      standardized practice patterns was associated with reduced resource use and
      improved patient outcomes. Most surgeons had very high compliance with the CPG.

PMID- 27027264
TI  - Coordination between respiration and swallowing during non-invasive positive
      pressure ventilation.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to test the hypothesis
      that the risk of silent aspiration is increased in non-invasive positive pressure
      ventilation. METHODS: We analysed the coordination between respiration and
      swallowing, in 12 young volunteers and 10 elder volunteers, by simultaneously
      monitoring respiratory flow, laryngeal movement and swallowing sound in three
      different conditions: control, continuous positive airway pressure (CPAP), and bi
      level positive airway pressure (BiPAP). A step-wise multiple regression analysis
      was performed with the occurrence rate of inspiration after swallows as the
      dependent variable and various correlated variables as the independent variables.
      RESULTS: In both subject groups, the occurrence rate of inspiration after swallow
      was greater with BiPAP compared with control and CPAP conditions. Repetitive
      saliva swallowing test count and swallow non-inspiratory flow occurrence rate
      were extracted as predictor variables for risk of inspiration after swallows
      during BiPAP treatment. CONCLUSION: We found that the occurrence rate of
      inspiration after swallow is increased with BiPAP use irrespective of age. The
      results suggest that swallow non-inspiratory flow may trigger inspiratory support
      in the BiPAP mode, resulting in a risk of aspiration.

PMID- 27027265
TI  - Exposure assessment of one-year-old child to 3G tablet in uplink mode and to 3G
      femtocell in downlink mode using polynomial chaos decomposition.
AB  - So far, the assessment of the exposure of children, in the ages 0-2 years old, to
      relatively new radio-frequency (RF) technologies, such as tablets and femtocells,
      remains an open issue. This study aims to analyse the exposure of a one year-old
      child to these two sources, tablets and femtocells, operating in uplink (tablet)
      and downlink (femtocell) modes, respectively. In detail, a realistic model of an
      infant has been used to model separately the exposures due to (i) a 3G tablet
      emitting at the frequency of 1940 MHz (uplink mode) placed close to the body and
      (ii) a 3G femtocell emitting at 2100 MHz (downlink mode) placed at a distance of
      at least 1 m from the infant body. For both RF sources, the input power was set
      to 250 mW. The variability of the exposure due to the variation of the position
      of the RF sources with respect to the infant body has been studied by stochastic
      dosimetry, based on polynomial chaos to build surrogate models of both whole-body
      and tissue specific absorption rate (SAR), which makes it easy and quick to
      investigate the exposure in a full range of possible positions of the sources.
      The major outcomes of the study are: (1) the maximum values of the whole-body SAR
      (WB SAR) have been found to be 9.5 mW kg(-1) in uplink mode and 65 MUW kg(-1) in
      downlink mode, i.e. within the limits of the ICNIRP 1998 Guidelines; (2) in both
      uplink and downlink mode the highest SAR values were approximately found in the
      same tissues, i.e. in the skin, eye and penis for the whole-tissue SAR and in the
      bone, skin and muscle for the peak SAR; (3) the change in the position of both
      the 3G tablet and the 3G femtocell significantly influences the infant exposure. 

PMID- 27027266
TI  - Applying the dark diversity concept to nature conservation.
AB  - Linking diversity to biological processes is central for developing informed and
      effective conservation decisions. Unfortunately, observable patterns provide only
      a proportion of the information necessary for fully understanding the mechanisms
      and processes acting on a particular population or community. We suggest
      conservation managers use the often overlooked information relative to species
      absences and pay particular attention to dark diversity (i.e., a set of species
      that are absent from a site but that could disperse to and establish there, in
      other words, the absent portion of a habitat-specific species pool). Together
      with existing ecological metrics, concepts, and conservation tools, dark
      diversity can be used to complement and further develop conservation
      prioritization and management decisions through an understanding of biodiversity
      relativized by its potential (i.e., its species pool). Furthermore, through a
      detailed understanding of the population, community, and functional dark
      diversity, the restoration potential of degraded habitats can be more rigorously
      assessed and so to the likelihood of successful species invasions. We suggest the
      application of the dark diversity concept is currently an underappreciated source
      of information that is valuable for conservation applications ranging from
      macroscale conservation prioritization to more locally scaled restoration ecology
      and the management of invasive species.

PMID- 27027267
TI  - Programmed Lab Experiments for Biochemical Investigation of Quorum-Sensing Signal
      Molecules in Rhizospheric Soil Bacteria.
AB  - Biochemistry courses in the Department of Molecular Biology at the National
      University of Rio Cuarto, Argentina, are designed for undergraduate students in
      biology, microbiology, chemistry, agronomy, and veterinary medicine. Microbiology
      students typically have previous coursework in general, analytical, and organic
      chemistry. Programmed sequences of lab experiments allow these students to
      investigate biochemical problems whose solution is feasible within the context of
      their knowledge and experience. We previously designed and reported a programmed
      lab experiment that familiarizes microbiology students with techniques for
      detection and characterization of quorum-sensing (QS) and quorum-quenching (QQ)
      signal molecules. Here, we describe a sequence of experiments designed to expand
      the understanding and capabilities of biochemistry students using techniques for
      extraction and identification of QS and QQ signal molecules from peanut
      rhizospheric soil bacteria, including culturing and manipulation of bacteria
      under sterile conditions. The program provides students with an opportunity to
      perform useful assays, draw conclusions from their results, and discuss possible
      extensions of the study. (c) 2016 by The International Union of Biochemistry and
      Molecular Biology, 44:256-262, 2016.

PMID- 27027269
TI  - Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases
      and hepatomegaly due to glycogenic hepatopathy.
AB  - Poorly controlled diabetes mellitus (DM) patients sometimes show serum
      transaminase elevations due to steatohepatitis. However, we experienced four
      cases with type 1 DM with sharp elevations in serum transaminases that could not
      be explained by steatohepatitis alone and showed bright liver. They were
      diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four
      patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year
      histories of type 1 DM and showed marked increases in serum transaminases
      (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255
      U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was
      12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis.
      Hepatomegaly and hyperdense liver were seen on computed tomography scans.
      Magnetic resonance imaging showed low intensity in T2-weighted images. The
      pathological findings revealed pale and swollen hepatocytes and glycogenated
      nuclei. The architecture of the liver was preserved, and steatosis and fibrosis
      were mild. The cytoplasm of hepatocytes stained densely positive with periodic
      acid-Schiff, and the positive staining disappeared after diastase digestion,
      suggesting glycogen deposition. No other cause of hepatitis was evident, and the
      diagnosis was GH. Elevated transaminases improved within 1 month with good
      glycemic control. Transaminase elevations were observed several times in three
      cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely
      high serum elevations of transaminases are important to identify clinically.
      Despite showing a good clinical course in general, GH sometimes recurs and
      requires strict glycemic control. Clinicians should be aware of and recognize GH
      when dealing with uncontrolled DM patients.

PMID- 27027270
TI  - Genotyping of microsatellite markers to study genetic structure of the wild
      striped snakehead Channa striata in Malaysia.
AB  - Genetic variability and differences in wild striped snakehead Channa striata from
      Malaysia were analysed by genotyping nine novel nuclear microsatellite loci.
      Analysis revealed moderate-to-high genetic diversity in most of the populations,
      indicative of large effective population sizes. The highly diversified
      populations are admixed populations and, therefore, can be recommended as
      potential candidates for selective breeding and conservation since they each
      contain most of the alleles found in their particular region. Three homogenous
      groups of the wild populations were identified, apparently separated by effective
      barriers, in accordance with contemporary drainage patterns. The highest
      population pairwise FST found between members of the same group reflects the
      ancient population connectivity; yet prolonged geographical isolation resulted in
      adaptation of alleles to local contemporary environmental change. A significant
      relationship between genetic distance and geographical isolation was observed (r
      = 0.644, P < 0.01). Anthropogenic perturbations indicated apparent genetic
      proximity between distant populations. 

PMID- 27027271
TI  - Atypical Chordae Tendineae of the Canine (Canis familiaris) Right
      Atrioventricular Valve.
AB  - The canine right atrioventricular valve cusps are anchored to papillary muscles
      by chordae tendineae. During ventricular systole, these tendineae keep the cusps
      from being pushed into the atrium. While this is the general description for
      chordae tendineae, several researchers have briefly documented chordae tendineae
      in animal and human hearts that do not attach to papillary muscles. In the 39
      canine hearts examined, atypical chordae tendineae were observed in two hearts.
      In both dogs, a single stranded chordae tendineae extended from the free edge of
      the parietal cusp of the right atrioventricular valve to the ventricular free
      wall. While the discovery of these atypical tendineae provides additional
      information on canine cardiac anatomy, their presence may also be clinically
      significant. A review of the veterinary and biomedical literature showed
      entanglement in normal chordae tendineae can be a complication during cardiac
      catheterization or pacemaker lead placement. Given this issue with normal chordae
      tendineae, it seems logical to propose that these atypical tendineae could also
      cause catheter or pacemaker lead entanglement and therefore warrant further study
      and documentation.

PMID- 27027272
TI  - Treatment of Cannabis Use Disorder: Current Science and Future Outlook.
AB  - Cannabis is the most commonly used illicit substance in the United States. Rates
      of cannabis use and cannabis use disorder (CUD) have increased in the past
      decade, paralleling changes in the legal and political climate favoring
      legalization. Almost 20 million people 12 years or older report past-month
      cannabis use, and 8 million report daily or near-daily use. Concurrently, the
      perception that cannabis use poses a significant risk of negative consequences
      has decreased. Contrary to this perception, heavy cannabis use is associated with
      cognitive impairment, increased risk for psychotic disorders and other mental
      health problems, lower education attainment, and unemployment. Clinical trials of
      various treatments for CUD have likewise increased, focusing primarily on
      psychotherapy treatments, specifically motivational enhancement therapy,
      cognitive behavioral therapy, and contingency management. Their findings suggest
      that a combination of these three modalities produces the best abstinence
      outcomes, although abstinence rates remain modest and decline after treatment.
      More recently, pharmacotherapy trials have been conducted as adjunctive
      interventions to psychosocial treatment. N-acetylcysteine and gabapentin are two
      of the most promising medications, although no pharmacologic treatment has
      emerged as clearly efficacious. In this review, we provide a detailed summary of
      clinical trials that evaluated psychotherapy and pharmacotherapy for treating CUD
      and discuss emerging areas of clinical research and cannabis-specific barriers to
      treatment.

PMID- 27027273
TI  - The use of direct analysis in real time (DART) to assess the levels of inhibitors
      co-extracted with DNA and the associated impact in quantification and
      amplification.
AB  - The measure of quality in DNA sample processing starts with an effective nucleic
      acid isolation procedure. Most problems with DNA sample typing can be attributed
      to low quantity DNA and/or to the presence of inhibitors in the sample.
      Therefore, establishing which isolation method is best at removing potential
      inhibitors may help overcome some of the problems analysts encounter by providing
      useful information in the determination of the optimal approach for any given
      sample. Direct analysis in real time (DART) mass spectrometry was used in this
      study to investigate the ability of different extraction methods to remove PCR
      inhibitors. Methods investigated included both liquid/liquid (phenol-chloroform)
      and solid phase based robotic procedures, (PrepFilerTM and EZ1 chemistries).
      Following extraction, samples were analyzed by DART in order to determine the
      level of remaining inhibitors and then quantified and amplified to determine the
      effect any remaining inhibitor had on the overall results. The data suggests that
      organic extraction methods result in detrimental amounts of phenol carryover
      while automated methods may produce carry-over of bile salts and other chemicals
      that preferentially bind the solid phase matrix. Both of these effects can have a
      negative impact in downstream sample processing and genotyping by PCR.

PMID- 27027274
TI  - A conduit between epidemiological research and regional health policy.
AB  - OBJECTIVE: To transform data from a research setting into a format that could be
      used to support strategies encouraging healthy lifestyle choices and service
      planning within local government. METHODS: Details of the health status and
      lifestyle behaviours of the Geelong, Victoria, population were generated
      independently by the Geelong Osteoporosis Study (GOS), a prospective population
      based cohort study. Recent GOS follow-up phases provided evidence about patterns
      of unhealthy diet, physical inactivity, smoking and harmful alcohol use. These
      factors are well-recognised modifiable risk factors for chronic disease; the
      dataset was complemented with prevalence estimates for musculoskeletal disease,
      obesity, diabetes, cardiovascular disease, asthma and cancer. RESULTS: Data were
      provided to Healthy Together Geelong in aggregate form according to age, sex and
      suburb. A population statistics company used the data to project health outcomes
      by suburb for use by local council. This data exchange served as a conduit
      between epidemiological research and policy development. CONCLUSION AND
      IMPLICATIONS: Regional policy makers were informed by local evidence, rather than
      national or state health survey, thereby optimising potential intervention
      strategies.

PMID- 27027275
TI  - Eye-sparing multidisciplinary approach for the management of lacrimal gland
      carcinoma.
AB  - BACKGROUND: We analyzed local control and early ocular toxicity after eye-sparing
      management of lacrimal gland carcinoma. METHODS: For consecutive patients with
      lacrimal gland carcinoma treated during 2007 to 2014, we reviewed tumor
      characteristics, treatment details, ocular toxic effects, and recurrence.
      RESULTS: Twenty patients, median age 55 years, were treated for lacrimal gland
      carcinoma during the study period; 11 had globe-sparing surgery. Seven patients
      had adenoid cystic carcinoma, 2 had carcinoma ex pleomorphic adenoma, and 1 each
      had high-grade and low-grade adenocarcinoma. Ten patients underwent postoperative
      radiotherapy, median 60 Gy (range, 52-64 Gy), 6 with concurrent chemotherapy. At
      a median of 30 months after radiation, all patients had dry eye syndrome, and 1
      patient had severe corneal and conjunctival damage leading to enucleation. All 11
      patients were disease free at last contact, median follow-up after surgery of 33
      months. CONCLUSION: An eye-sparing approach with surgery followed by adjuvant
      radiotherapy or chemoradiotherapy is feasible for selected patients with lacrimal
      gland carcinoma and is associated with a reasonable locoregional control and
      ocular toxicity profile. (c) 2016 Wiley Periodicals, Inc. Head Neck 38:1258-1262,
      2016.

PMID- 27027276
TI  - Autophagy is dispensable to overcome ER stress in the filamentous fungus
      Aspergillus niger.
AB  - Secretory proteins are subjected to stringent quality control systems in the
      endoplasmic reticulum (ER) which include the targeting of misfolded proteins for
      proteasomal destruction via the ER-associated degradation (ERAD) pathway. Since
      deletion of ERAD genes in the filamentous fungus Aspergillus niger had hardly any
      effect on growth, this study investigates whether autophagy might function as an
      alternative process to eliminate misfolded proteins from the ER. We generated A.
      niger double mutants by deleting genes essential for ERAD (derA) and autophagy
      (atg1 or atg8), and assessed their growth both under normal and ER stress
      conditions. Sensitivity toward ER stress was examined by treatment with
      dithiothreitol (DTT) and by expressing a mutant form of glucoamylase
      (mtGlaA::GFP) in which disulfide bond sites in GlaA were mutated. Misfolding of
      mtGlaA::GFP was confirmed, as mtGlaA::GFP accumulated in the ER. Expression of
      mtGlaA::GFP in ERAD and autophagy mutants resulted in a twofold higher
      accumulation in DeltaderA and DeltaderADeltaatg1 strains compared to Deltaatg1
      and wild type. As DeltaderADeltaatg1 mutants did not show increased sensitivity
      toward DTT, not even when mtGlaA::GFP was expressed, the results indicate that
      autophagy does not act as an alternative pathway in addition to ERAD for removing
      misfolded proteins from the ER in A. niger.

PMID- 27027277
TI  - [Bipolar Sealing of Lung Veins with 5 mm and 10 mm Instruments - Bursting
      Pressures Measured in an Ex-Vivo Model].
AB  - BACKGROUND: In every anatomic lung resection, lung veins need to be sealed and
      divided. If open surgery is performed, veins are usually treated with ligatures.
      In minimally-invasive procedures a vascular stapler is used. Blood vessels can be
      securely closed with modern bipolar sealing technology. Since this method has
      rarely been used in lung veins, we carried out the present study on an ex-vivo
      model to test whether satisfactory bursting pressures can be achieved using 5 mm
      and 10 mm MARSEAL(r) sealing instruments. MATERIAL AND METHODS: The experimental
      investigations were carried out on heart-lung preparations (including both lungs)
      from freshly-slaughtered pigs (weight: 199 lbs). After the lung veins were
      dissected, three groups were formed according to size: group 1: 1-7 mm, group 2:
      8-10 mm and group 3: > 10 mm. Bipolar sealing was performed with a 5 mm or 10 mm
      MARSEAL(r) sealing device and the special SealSafe(r) G5 electric current.
      Vessels closed by simple ligation served as a control group. A pressure sensor
      was implanted into the unsealed end of the blood vessel. Air was pumped into the
      blood vessel and the bursting pressure - the pressure (in mbar) at which the
      vessel began to leak - was determined digitally. The mean bursting pressures were
      compared using the non-parametric Mann Whitney U test (the level of significance
      was p < 0.05). RESULTS: In group 1 the mean bursting pressures for the 5 mm and
      10 mm instruments were found to be 167.1 +/- 38.7 mbar and 113.8 +/- 23.3 mbar,
      respectively. Both were significantly inferior to the pressure of 178.8 +/- 44.5
      mbar achieved by the control group. In group 2 the bursting pressures were 122.7
      +/- 27.8 mbar with the 5 mm instrument and 93.5 +/- 39.6 mbar with the 10 mm
      instrument. The mean bursting pressure for the control group was 180.7 +/-
      35.8.mbar. In group 3 the mean bursting pressures were 98.2 +/- 28.8 mbar with
      the 5 mm instrument and 65.5 +/- 19.7 mbar with the 10 mm instrument. All
      attempts to seal the entire left atrium failed. CONCLUSION: In our ex-vivo model
      of lung veins, acceptable bursting pressures were achieved in blood vessels with
      a maximum diameter of 10 mm. Bipolar impedance-controlled sealing may create an
      adequate seal on pulmonary veins up to a diameter of 10 mm. The use of a 10 mm
      instrument has no advantage compared to a 5 mm instrument. Secure sealing of the
      left atrium is not possible.

PMID- 27027278
TI  - [Wolfgang Hepp - Meritorious Nestor of German Vascular Surgery and the
      Publicistic Part of Vascular Medicine (a Laudation)].

PMID- 27027279
TI  - [Infiltration of Cardiac Vessels by Lung Cancer: Incidence, Classification,
      Operative Technique with Heart Lung Bypass, and Results].
AB  - Carcinomas of the lung that infiltrate the blood vessels close to the heart (left
      atrium, pulmonary artery and aorta) without spreading to mediastinal lymph nodes
      or developing distant metastases are rare overall. Such situations are often
      classified as primarily inoperable by interdisciplinary tumour boards. This is
      only the case if, for technical reasons, an experienced thoracic surgeon does not
      feel able to perform a resection with a surrounding margin of healthy tissue. The
      surgical strategy to be employed must be chosen individually depending on the
      infiltrated structure. Complete tumour staging should always be carried out. This
      also helps in deciding whether neoadjuvant chemotherapy should be given before
      resection. A heart-lung machine must always be used if larger defects occur due
      to the resection of blood vessels close to the heart. Using a heart-lung machine
      in the case of tumour resection does not lead to problems of tumour cell
      dissemination. Nevertheless, the duration of use of the heart-lung machine should
      be kept to a minimum, also because of the anticoagulation required. The cardiac
      defects can be closed securely with the bovine patching materials that are now
      available. Postoperative morbidity and mortality are low after such resections.
      Curative resection of blood vessels close to the heart infiltrated by carcinomas
      of the lung can lead to 5-year survival rates of up to 50 %.

PMID- 27027280
TI  - Current and historical involvement of dentistry in child protection and a glimpse
      of the future.
AB  - Dental teams have been involved with child protection for over 40 years. This
      brief review summarises their involvement in the detection of various types of
      child abuse and goes on to discuss the gap between the proportions of dental
      professionals who suspect child abuse or neglect in their paediatric patients and
      those who refer such cases on. Potential reasons for this discrepancy are
      discussed, and a glimpse of the future is given as to where further research may
      be necessary to tackle this existing gap. 

PMID- 27027281
TI  - Discovery of a Promiscuous Non-Heme Iron Halogenase in Ambiguine Alkaloid
      Biogenesis: Implication for an Evolvable Enzyme Family for Late-Stage
      Halogenation of Aliphatic Carbons in Small Molecules.
AB  - The elucidation of enigmatic enzymatic chlorination timing in ambiguine indole
      alkaloid biogenesis led to the discovery and characterization of AmbO5 protein as
      a promiscuous non-heme iron aliphatic halogenase. AmbO5 was shown capable of
      selectively modifying seven structurally distinct ambiguine, fischerindole and
      hapalindole alkaloids with chlorine via late-stage aliphatic C-H group
      functionalization. Cross-comparison of AmbO5 with a previously characterized
      aliphatic halogenase homolog WelO5 that has a restricted substrate scope led to
      the identification of a C-terminal sequence motif important for substrate
      tolerance and specificity. Mutagenesis of 18 residues of WelO5 within the
      identified sequence motif led to a functional mutant with an expanded substrate
      scope identical to AmbO5, but an altered substrate specificity from the wild-type
      enzymes. These observations collectively provide evidence on the evolvable nature
      of AmbO5/WelO5 enzyme duo in the context of hapalindole-type alkaloid biogenesis
      and implicate their promise for the future development of designer biocatalysis
      for the selective late-stage modification of unactivated aliphatic carbon centers
      in small molecules with halogens.

PMID- 27027282
TI  - DNA methylation on N(6)-adenine in mammalian embryonic stem cells.
AB  - It has been widely accepted that 5-methylcytosine is the only form of DNA
      methylation in mammalian genomes. Here we identify N(6)-methyladenine as another
      form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a
      demethylase for N(6)-methyladenine. An increase of N(6)-methyladenine levels in
      Alkbh1-deficient cells leads to transcriptional silencing. N(6)-methyladenine
      deposition is inversely correlated with the evolutionary age of LINE-1
      transposons; its deposition is strongly enriched at young (<1.5 million years
      old) but not old (>6 million years old) L1 elements. The deposition of N(6)
      methyladenine correlates with epigenetic silencing of such LINE-1 transposons,
      together with their neighbouring enhancers and genes, thereby resisting the gene
      activation signals during embryonic stem cell differentiation. As young full
      length LINE-1 transposons are strongly enriched on the X chromosome, genes
      located on the X chromosome are also silenced. Thus, N(6)-methyladenine developed
      a new role in epigenetic silencing in mammalian evolution distinct from its role
      in gene activation in other organisms. Our results demonstrate that N(6)
      methyladenine constitutes a crucial component of the epigenetic regulation
      repertoire in mammalian genomes. 

PMID- 27027283
TI  - A map of the large day-night temperature gradient of a super-Earth exoplanet.
AB  - Over the past decade, observations of giant exoplanets (Jupiter-size) have
      provided key insights into their atmospheres, but the properties of lower-mass
      exoplanets (sub-Neptune) remain largely unconstrained because of the challenges
      of observing small planets. Numerous efforts to observe the spectra of super
      Earths--exoplanets with masses of one to ten times that of Earth--have so far
      revealed only featureless spectra. Here we report a longitudinal thermal
      brightness map of the nearby transiting super-Earth 55 Cancri e (refs 4, 5)
      revealing highly asymmetric dayside thermal emission and a strong day-night
      temperature contrast. Dedicated space-based monitoring of the planet in the
      infrared revealed a modulation of the thermal flux as 55 Cancri e revolves around
      its star in a tidally locked configuration. These observations reveal a hot spot
      that is located 41 +/- 12 degrees east of the substellar point (the point at
      which incident light from the star is perpendicular to the surface of the
      planet). From the orbital phase curve, we also constrain the nightside brightness
      temperature of the planet to 1,380 +/- 400 kelvin and the temperature of the
      warmest hemisphere (centred on the hot spot) to be about 1,300 kelvin hotter
      (2,700 +/- 270 kelvin) at a wavelength of 4.5 micrometres, which indicates
      inefficient heat redistribution from the dayside to the nightside. Our
      observations are consistent with either an optically thick atmosphere with heat
      recirculation confined to the planetary dayside, or a planet devoid of atmosphere
      with low-viscosity magma flows at the surface.

PMID- 27027285
TI  - Microbiology: Fungus produces a toxic surprise.

PMID- 27027284
TI  - Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4
      signalling.
AB  - Cerebral cavernous malformations (CCMs) are common inherited and sporadic
      vascular malformations that cause strokes and seizures in younger individuals.
      CCMs arise from endothelial cell loss of KRIT1, CCM2 or PDCD10, non-homologous
      proteins that form an adaptor complex. How disruption of the CCM complex results
      in disease remains controversial, with numerous signalling pathways (including
      Rho, SMAD and Wnt/beta-catenin) and processes such as endothelial-mesenchymal
      transition (EndMT) proposed to have causal roles. CCM2 binds to MEKK3 (refs 7, 8,
      9, 10, 11), and we have recently shown that CCM complex regulation of MEKK3 is
      essential during vertebrate heart development. Here we investigate this mechanism
      in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we show
      that expression of the MEKK3 target genes Klf2 and Klf4, as well as Rho and
      ADAMTS protease activity, are increased in the endothelial cells of early CCM
      lesions. By contrast, we find no evidence of EndMT or increased SMAD or Wnt
      signalling during early CCM formation. Endothelial-specific loss of Map3k3 (also
      known as Mekk3), Klf2 or Klf4 markedly prevents lesion formation, reverses the
      increase in Rho activity, and rescues lethality. Consistent with these findings
      in mice, we show that endothelial expression of KLF2 and KLF4 is increased in
      human familial and sporadic CCM lesions, and that a disease-causing human CCM2
      mutation abrogates the MEKK3 interaction without affecting CCM complex formation.
      These studies identify gain of MEKK3 signalling and KLF2/4 function as causal
      mechanisms for CCM pathogenesis that may be targeted to develop new CCM
      therapeutics.

PMID- 27027286
TI  - Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in
      Indonesia.
AB  - Homo floresiensis, a primitive hominin species discovered in Late Pleistocene
      sediments at Liang Bua (Flores, Indonesia), has generated wide interest and
      scientific debate. A major reason this taxon is controversial is because the H.
      floresiensis-bearing deposits, which include associated stone artefacts and
      remains of other extinct endemic fauna, were dated to between about 95 and 12
      thousand calendar years (kyr) ago. These ages suggested that H. floresiensis
      survived until long after modern humans reached Australia by ~50 kyr ago. Here we
      report new stratigraphic and chronological evidence from Liang Bua that does not
      support the ages inferred previously for the H. floresiensis holotype (LB1), ~18
      thousand calibrated radiocarbon years before present (kyr cal. BP), or the time
      of last appearance of this species (about 17 or 13-11 kyr cal. BP). Instead, the
      skeletal remains of H. floresiensis and the deposits containing them are dated to
      between about 100 and 60 kyr ago, whereas stone artefacts attributable to this
      species range from about 190 to 50 kyr in age. Whether H. floresiensis survived
      after 50 kyr ago--potentially encountering modern humans on Flores or other
      hominins dispersing through southeast Asia, such as Denisovans--is an open
      question.

PMID- 27027287
TI  - Regeneration: Not everything is scary about a glial scar.

PMID- 27027288
TI  - Astrocyte scar formation aids central nervous system axon regeneration.
AB  - Transected axons fail to regrow in the mature central nervous system. Astrocytic
      scars are widely regarded as causal in this failure. Here, using three
      genetically targeted loss-of-function manipulations in adult mice, we show that
      preventing astrocyte scar formation, attenuating scar-forming astrocytes, or
      ablating chronic astrocytic scars all failed to result in spontaneous regrowth of
      transected corticospinal, sensory or serotonergic axons through severe spinal
      cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel
      depots of required axon-specific growth factors not present in SCI lesions, plus
      growth-activating priming injuries, stimulated robust, laminin-dependent sensory
      axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI
      lesions. Preventing astrocytic scar formation significantly reduced this
      stimulated axon regrowth. RNA sequencing revealed that astrocytes and non
      astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules.
      Our findings show that contrary to the prevailing dogma, astrocyte scar formation
      aids rather than prevents central nervous system axon regeneration. 

PMID- 27027289
TI  - Animal behaviour: Some begging is actually bragging.

PMID- 27027291
TI  - Late Quaternary climate change shapes island biodiversity.
AB  - Island biogeographical models consider islands either as geologically static with
      biodiversity resulting from ecologically neutral immigration-extinction dynamics,
      or as geologically dynamic with biodiversity resulting from immigration
      speciation-extinction dynamics influenced by changes in island characteristics
      over millions of years. Present climate and spatial arrangement of islands,
      however, are rather exceptional compared to most of the Late Quaternary, which is
      characterized by recurrent cooler and drier glacial periods. These climatic
      oscillations over short geological timescales strongly affected sea levels and
      caused massive changes in island area, isolation and connectivity, orders of
      magnitude faster than the geological processes of island formation, subsidence
      and erosion considered in island theory. Consequences of these oscillations for
      present biodiversity remain unassessed. Here we analyse the effects of present
      and Last Glacial Maximum (LGM) island area, isolation, elevation and climate on
      key components of angiosperm diversity on islands worldwide. We find that post
      LGM changes in island characteristics, especially in area, have left a strong
      imprint on present diversity of endemic species. Specifically, the number and
      proportion of endemic species today is significantly higher on islands that were
      larger during the LGM. Native species richness, in turn, is mostly determined by
      present island characteristics. We conclude that an appreciation of Late
      Quaternary environmental change is essential to understand patterns of island
      endemism and its underlying evolutionary dynamics. 

PMID- 27027290
TI  - Structural basis of cohesin cleavage by separase.
AB  - Accurate chromosome segregation requires timely dissolution of chromosome
      cohesion after chromosomes are properly attached to the mitotic spindle. Separase
      is absolutely essential for cohesion dissolution in organisms from yeast to man.
      It cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow
      chromosome segregation. Cohesin cleavage is spatiotemporally controlled by
      separase-associated regulatory proteins, including the inhibitory chaperone
      securin, and by phosphorylation of both the enzyme and substrates. Dysregulation
      of this process causes chromosome missegregation and aneuploidy, contributing to
      cancer and birth defects. Despite its essential functions, atomic structures of
      separase have not been determined. Here we report crystal structures of the
      separase protease domain from the thermophilic fungus Chaetomium thermophilum,
      alone or covalently bound to unphosphorylated and phosphorylated inhibitory
      peptides derived from a cohesin cleavage site. These structures reveal how
      separase recognizes cohesin and how cohesin phosphorylation by polo-like kinase 1
      (Plk1) enhances cleavage. Consistent with a previous cellular study, mutating two
      securin residues in a conserved motif that partly matches the separase cleavage
      consensus converts securin from a separase inhibitor to a substrate. Our study
      establishes atomic mechanisms of substrate cleavage by separase and suggests
      competitive inhibition by securin. 

PMID- 27027292
TI  - Island biogeography: Shaped by sea-level shifts.

PMID- 27027293
TI  - Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia.
AB  - Colonic epithelial cells are covered by thick inner and outer mucus layers. The
      inner mucus layer is free of commensal microbiota, which contributes to the
      maintenance of gut homeostasis. In the small intestine, molecules critical for
      prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti
      microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have
      been identified. Although there are mucus layers providing physical barriers
      against the large number of microbiota present in the large intestine, the
      mechanisms that separate bacteria and colonic epithelia are not fully elucidated.
      Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents
      flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively
      expressed in epithelial cells at the uppermost layer of the large intestinal
      gland, was secreted into the lumen and bound flagellated bacteria including
      Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner
      mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were
      highly sensitive to intestinal inflammation induced by dextran sulfate sodium
      (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the
      bacterial-free state of the inner mucus layer and ameliorated DSS-induced
      intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and
      suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of
      intestinal bacteria and epithelial cells in the colon to preserve intestinal
      homeostasis. 

PMID- 27027294
TI  - Epigenetics: An elusive DNA base in mammals.

PMID- 27027295
TI  - Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of
      UCP1.
AB  - Brown and beige adipose tissues can dissipate chemical energy as heat through
      thermogenic respiration, which requires uncoupling protein 1 (UCP1).
      Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging
      investigation of factors that control UCP1-dependent respiration in vivo. Here we
      show that acutely activated thermogenesis in brown adipose tissue is defined by a
      substantial increase in levels of mitochondrial reactive oxygen species (ROS).
      Remarkably, this process supports in vivo thermogenesis, as pharmacological
      depletion of mitochondrial ROS results in hypothermia upon cold exposure, and
      inhibits UCP1-dependent increases in whole-body energy expenditure. We further
      establish that thermogenic ROS alter the redox status of cysteine thiols in brown
      adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key
      target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this
      site desensitizes the purine-nucleotide-inhibited state of the carrier to
      adrenergic activation and uncoupling. These studies identify mitochondrial ROS
      induction in brown adipose tissue as a mechanism that supports UCP1-dependent
      thermogenesis and whole-body energy expenditure, which opens the way to improved
      therapeutic strategies for combating metabolic disorders.

PMID- 27027297
TI  - Accommodative and binocular dysfunctions: prevalence in a randomised sample of
      university students.
AB  - BACKGROUND: The aim was to analyse the prevalence of symptomatic accommodative
      and non-strabismic binocular dysfunctions in a randomised population of
      university subjects. METHODS: A cross-sectional study was conducted with a
      randomised sample of 175 university students aged between 18 and 35 years. All
      subjects were given a visual examination in which their symptoms were recorded,
      as well as performing objective and subjective refractive examinations and
      accommodative and binocular tests. Each subject was tested for the presence of
      uncorrected refractive error. Accommodative dysfunctions (AD) and binocular
      dysfunctions (BD) were diagnosed according to the number of clinical signs
      associated with each disorder, considering the signs that could be associated
      with each dysfunction as fundamental or complementary. An accommodative or
      binocular dysfunction was diagnosed when the subjects met two conditions:
      presenting with any kind of visual symptom in their clinical history and
      presenting the fundamental sign associated with each dysfunction as well as two
      or more complementary signs. Those subjects who presented with only an
      uncorrected refractive error were considered within the group called refractive
      dysfunction (RD). RESULTS: The overall prevalence of accommodative and/or
      binocular dysfunctions was 13.15 per cent and for refractive dysfunction it was
      45.14 per cent. Accommodative dysfunctions were present in 2.29 per cent of the
      population, binocular dysfunctions were observed in eight per cent and
      accommodative dysfunctions together were found in 2.86 per cent of the university
      students. Within the accommodative and binocular disorders, the most prevalent
      dysfunctions were convergence insufficiency, with a prevalence of 3.43 per cent
      and convergence excess and accommodation excess, both with a prevalence of 2.29
      per cent. CONCLUSION: Binocular dysfunctions were more prevalent than
      accommodative dysfunctions or accommodative and binocular dysfunctions together
      in a randomised population of university students.

PMID- 27027298
TI  - Quantitative Probing of Cu(2+) Ions Naturally Present in Single Living Cells.
AB  - Quantitative probing of Cu(2+) ions naturally present in single living cells is
      realized by developing a quantum-dot-embedded nanowire-waveguide probe. The
      intracellular Cu(2+) ion concentration is quantified by direct monitoring of
      photoluminescence quenching during the insertion of the nanowire in a living
      neuron. The measured intracellular Cu(2+) ion concentration is 3.34 +/- 1.04 *
      10(-6) m (mean +/- s.e.m.) in single hippocampal neurons. 

PMID- 27027296
TI  - Candidalysin is a fungal peptide toxin critical for mucosal infection.
AB  - Cytolytic proteins and peptide toxins are classical virulence factors of several
      bacterial pathogens which disrupt epithelial barrier function, damage cells and
      activate or modulate host immune responses. Such toxins have not been identified
      previously in human pathogenic fungi. Here we identify the first, to our
      knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida
      albicans. This secreted toxin directly damages epithelial membranes, triggers a
      danger response signalling pathway and activates epithelial immunity. Membrane
      permeabilization is enhanced by a positive charge at the carboxy terminus of the
      peptide, which triggers an inward current concomitant with calcium influx. C.
      albicans strains lacking this toxin do not activate or damage epithelial cells
      and are avirulent in animal models of mucosal infection. We propose the name
      'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical
      molecular determinant of epithelial damage and host recognition of the clinically
      important fungus, C. albicans. 

PMID- 27027299
TI  - Surgical treatment for diabetic vitreoretinal diseases: a review.
AB  - Over the past four decades, advancements in surgical instrumentations and
      techniques have significantly improved the postoperative anatomical and visual
      outcomes of patients with various diabetic vitreoretinal diseases. In particular,
      surgical interventions for previously serious and untreatable blinding
      proliferative diabetic retinopathy can now be performed, with much better
      results. The advents of micro incisional vitrectomy system with better
      visualization system like binocular indirect ophthalmomicroscope and state-of-the
      art instrumentation revolutionized the era of diabetic vitrectomy. High-speed
      vitrectors, finer instruments, chromo-assisted vitrectomy and use of anti
      vascular endothelial growth factors not only change the paradigm but also help
      achieve much better outcome after diabetic vitrectomies. In this review, we will
      discuss and summarize the indications, surgical considerations, surgical
      techniques, potential complications and outcomes of vitreoretinal surgery for
      diabetic eye diseases. 

PMID- 27027300
TI  - Trehalose is required for stress resistance and virulence of the Basidiomycota
      plant pathogen Ustilago maydis.
AB  - Trehalose is an important disaccharide that can be found in bacteria, fungi,
      invertebrates and plants. In some Ascomycota fungal plant pathogens, the role of
      trehalose was recently studied and shown to be important for conferring
      protection against several environmental stresses and for virulence. In most of
      the fungi studied, two enzymes are involved in the synthesis of trehalose:
      trehalose-6-phosphate synthase (Tps1) and trehalose-6-phosphate phosphatase
      (Tps2). To study the role of trehalose in virulence and stress response in the
      Basidiomycota maize pathogen Ustilago maydis, Deltatps2 deletion mutants were
      constructed. These mutants did not produce trehalose as confirmed by HPLC
      analysis, showing that the single gene disruption impaired its biosynthesis. The
      mutants displayed increased sensitivity to oxidative, heat, acid, ionic and
      osmotic stresses as compared to the wild-type strains. Virulence of Deltatps2
      mutants to maize plants was extremely reduced compared to wild-type strains,
      possibly due to reduced capability to deal with the hostile host environment. The
      phenotypic traits displayed by Deltatps2 strains were fully restored to wild-type
      levels when complemented with the endogenous UmTPS2 gene, or a chimeric construct
      having the Saccharomyces cerevisiae TPS2 ORF. This report demonstrates the
      presence of a single biosynthetic pathway for trehalose, and its importance for
      virulence in this model Basidiomycota plant pathogen.

PMID- 27027301
TI  - The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of
      Rifaximin.
AB  - Antibiotics are mainly used in clinical practice for their activity against
      pathogens, but they also alter the composition of commensal gut microbial
      community. Rifaximin is a non-absorbable antibiotic with additional effects on
      the gut microbiota about which very little is known. It is still not clear to
      what extent rifaximin can be able to modulate gut microbiota composition and
      diversity in different clinical settings. Studies based on culture-dependent
      techniques revealed that rifaximin treatment promotes the growth of beneficial
      bacteria, such as Bifidobacteria and Lactobacilli. Accordingly, our metagenomic
      analysis carried out on patients with different gastrointestinal and liver
      diseases highlighted a significant increase in Lactobacilli after rifaximin
      treatment, persisting in the short time period. This result was independent of
      the disease background and was not accompanied by a significant alteration of the
      overall gut microbial ecology. This suggests that rifaximin can exert important
      eubiotic effects independently of the original disease, producing a favorable gut
      microbiota perturbation without changing its overall composition and diversity. 

PMID- 27027302
TI  - GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii.
AB  - Toxoplasma gondii is a widespread parasite responsible for causing clinical
      diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid
      induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the
      TNF receptor superfamily, is found to be expressed in various cell types of the
      immune system and provides an important costimulatory signal for T cells and
      myeloid cells. However, the precise role of this receptor in the context of T.
      gondii infection remains elusive. Therefore, the current study investigated the
      role of GITR activation in the immunoregulation mechanisms induced during the
      experimental infection of mice with T. gondii. Our data show that T. gondii
      infection slightly upregulates GITR expression in Treg cells and B cells, but the
      most robust increment in expression was observed in macrophages and dendritic
      cells. Interestingly, mice infected and treated with an agonistic antibody anti
      GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production
      at preferential sites of parasite replication, which was associated with the
      decrease in latent brain parasitism of mice under treatment with DTA-1. Several
      in vivo and in vitro analysis were performed to identify the cellular mechanisms
      involved in GITR activation upon infection, however no clear alterations were
      detected in the phenotype/function of macrophages, Tregs and B cells under
      treatment with DTA-1. Therefore, GITR appears as a potential target for
      intervention during infection by the parasite Toxoplasma gondii, even though
      further studies are still necessary to better characterize the immune response
      triggered by GITR activation during T. gondii infection. 

PMID- 27027303
TI  - Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with
      Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in
      Remote Tropical Settings.
AB  - BACKGROUND: Malaria accounts for a small fraction of febrile cases in
      increasingly large areas of the malaria endemic world. Point-of-care tests to
      improve the management of non-malarial fevers appropriate for primary care are
      few, consisting of either diagnostic tests for specific pathogens or testing for
      biomarkers of host response that indicate whether antibiotics might be required.
      The impact and cost-effectiveness of these approaches are relatively unexplored
      and methods to do so are not well-developed. METHODS: We model the ability of
      dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared
      with testing for elevated C-Reactive Protein (CRP), a biomarker of host
      inflammation. Using data on causes of fever in rural Laos, we estimate the
      proportion of outpatients that would be correctly classified as requiring an
      antibiotic and the likely cost-effectiveness of the approaches. RESULTS: Use of
      either pathogen-specific test slightly increased the proportion of patients
      correctly classified as requiring antibiotics. CRP testing was consistently
      superior to the pathogen-specific tests, despite heterogeneity in causes of
      fever. All testing strategies are likely to result in higher average costs, but
      only the scrub typhus and CRP tests are likely to be cost-effective when
      considering direct health benefits, with median cost per disability adjusted life
      year averted of approximately $48 USD and $94 USD, respectively. CONCLUSIONS:
      Testing for viral infections is unlikely to be cost-effective when considering
      only direct health benefits to patients. Testing for prevalent bacterial
      pathogens can be cost-effective, having the benefit of informing not only whether
      treatment is required, but also as to the most appropriate antibiotic; this
      advantage, however, varies widely in response to heterogeneity in causes of
      fever. Testing for biomarkers of host inflammation is likely to be consistently
      cost-effective despite high heterogeneity, and can also offer substantial
      reductions in over-use of antimicrobials in viral infections.

PMID- 27027304
TI  - Osteology Supports a Stem-Galliform Affinity for the Giant Extinct Flightless
      Bird Sylviornis neocaledoniae (Sylviornithidae, Galloanseres).
AB  - The giant flightless bird Sylviornis neocaledoniae (Aves: Sylviornithidae)
      existed on La Grande Terre and Ile des Pins, New Caledonia, until the late
      Holocene when it went extinct shortly after human arrival on these islands. The
      species was generally considered to be a megapode (Megapodiidae) until the family
      Sylviornithidae was erected for it in 2005 to reflect multiple cranial
      autapomorphies. However, despite thousands of bones having been reported for this
      unique and enigmatic taxon, the postcranial anatomy has remained largely unknown.
      We rectify this deficiency and describe the postcranial skeleton of S.
      neocaledoniae based on ~600 fossils and use data from this and its cranial
      anatomy to make a comprehensive assessment of its phylogenetic affinities.
      Sylviornis neocaledoniae is found to be a stem galliform, distant from
      megapodiids, and the sister taxon to the extinct flightless Megavitiornis
      altirostris from Fiji, which we transfer to the family Sylviornithidae. These two
      species form the sister group to extant crown-group galliforms. Several other
      fossil galloanseres also included in the phylogenetic analysis reveal novel
      hypotheses of their relationships as follows: Dromornis planei (Dromornithidae)
      is recovered as a stem galliform rather than a stem anseriform; Presbyornis
      pervetus (Presbyornithidae) is the sister group to Anseranatidae, not to
      Anatidae; Vegavis iaai is a crown anseriform but remains unresolved relative to
      Presbyornis pervetus, Anseranatidae and Anatidae. Sylviornis neocaledoniae was
      reconstructed herein to be 0.8 m tall in a resting stance and weigh 27-34 kg. The
      postcranial anatomy of S. neocaledoniae shows no indication of the specialised
      adaptation to digging seen in megapodiids, with for example, its ungual
      morphology differing little from that of chicken Gallus gallus. These
      observations and its phylogenetic placement as stem galliforms makes it
      improbable that this species employed ectothermic incubation or was a mound
      builder. Sylviornis neocaledoniae can therefore be excluded as the constructor of
      tumuli in New Caledonia. 

PMID- 27027305
TI  - The Evolution of Musical Diversity: The Key Role of Vertical Transmission.
AB  - Music, like languages, is one of the key components of our culture, yet musical
      evolution is still poorly known. Numerous studies using computational methods
      derived from evolutionary biology have been successfully applied to varied subset
      of linguistic data. One of the major drawback regarding musical studies is the
      lack of suitable coded musical data that can be analysed using such evolutionary
      tools. Here we present for the first time an original set of musical data coded
      in a way that enables construction of trees classically used in evolutionary
      approaches. Using phylogenetic methods, we test two competing theories on musical
      evolution: vertical versus horizontal transmission. We show that, contrary to
      what is currently believed, vertical transmission plays a key role in shaping
      musical diversity. The signal of vertical transmission is particularly strong for
      intrinsic musical characters such as metrics, rhythm, and melody. Our findings
      reveal some of the evolutionary mechanisms at play for explaining musical
      diversity and open a new field of investigation in musical evolution. 

PMID- 27027306
TI  - Short-Term Effects of Phenobarbitone on Electrographic Seizures in Neonates.
AB  - BACKGROUND: Phenobarbitone is the most common first-line anti-seizure drug and is
      effective in approximately 50% of all neonatal seizures. OBJECTIVE: To describe
      the response of electrographic seizures to the administration of intravenous
      phenobarbitone in neonates using seizure burden analysis techniques. METHODS:
      Multi-channel conventional EEG, reviewed by experts, was used to determine the
      electrographic seizure burden in hourly epochs. The maximum seizure burden
      evaluated 1 h before each phenobarbitone dose (T-1) was compared to seizure
      burden in periods of increasing duration after each phenobarbitone dose had been
      administered (T+1, T+2 to seizure offset). Differences were analysed using linear
      mixed models and summarized as means and 95% CI. RESULTS: Nineteen neonates had
      electrographic seizures and met the inclusion criteria for the study. Thirty-one
      doses were studied. The maximum seizure burden was significantly reduced 1 h
      after the administration of phenobarbitone (T+1) [-14.0 min/h (95% CI: -19.6, 
      8.5); p < 0.001]. The percentage reduction was 74% (IQR: 36-100). This reduction
      was temporary and not significant within 4 h of administrating phenobarbitone.
      Subgroup analysis showed that only phenobarbitone doses at 20 mg/kg resulted in a
      significant reduction in the maximum seizure burden from T-1 to T+1 (p = 0.002).
      CONCLUSIONS: Phenobarbitone significantly reduced seizures within 1 h of
      administration as assessed with continuous multi-channel EEG monitoring in
      neonates. The reduction was not permanent and seizures were likely to return
      within 4 h of treatment.

PMID- 27027308
TI  - Development of a Prognostic Nomogram for Patients with Peritoneally Metastasized
      Colorectal Cancer Treated with Cytoreductive Surgery and HIPEC.
AB  - BACKGROUND: With the introduction of cytoreductive surgery (CRS) and hyperthermic
      intraperitoneal chemotherapy (HIPEC), long-term survival can be achieved in
      selected patients with colorectal peritoneal metastases (PM). Patient selection
      and outcome may be improved significantly with a tool that adequately predicts
      survival in these patients. This study was designed to validate the peritoneal
      surface disease severity score (PSDSS) in patients with colorectal PM treated
      with CRS + HIPEC. If performance of the PSDSS was suboptimal (c < 0.7), we aimed
      to develop a new prognostic model. METHODS: Patients were included if they had
      colorectal PM and underwent CRS + HIPEC with intended complete cytoreduction in a
      Dutch tertiary hospital between 2007 and 2015. Statistical analyses were
      performed with R-software. RESULTS: A total of 200 patients underwent CRS +
      HIPEC. External validation of the PSDSS showed a Harrell's c statistic of 0.62.
      After analysis, four parameters appeared prognostically relevant factors for
      overall survival: age, PCI score, locoregional lymph node status, and signet ring
      cell histology. The weighted relevance of these parameters was turned into a
      prognostic nomogram that we termed colorectal peritoneal metastases prognostic
      surgical score (COMPASS). The COMPASS differentiated well and showed a Harrell's
      c statistic of 0.72 with a calibration plot showing good agreement. CONCLUSIONS:
      This study externally validated the PSDSS and developed a new prognostic score,
      the COMPASS. This pre-cytoreduction nomogram was more accurate than PSDSS in
      predicting survival of patients undergoing CRS + HIPEC. It can be used as tool to
      assist in the decision about continuing cytoreduction and HIPEC and can provide
      valuable information in the follow-up period after CRS + HIPEC.

PMID- 27027307
TI  - Comparative Proteomics Identifies Host Immune System Proteins Affected by
      Infection with Mycobacterium bovis.
AB  - Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact
      human and animal health worldwide. The mycobacterial life cycle is complex, and
      the mechanisms resulting in pathogen infection and survival in host cells are not
      fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for
      MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild
      boar TB model, mycobacterial infection affects the expression of innate and
      adaptive immune response genes in mandibular lymph nodes and oropharyngeal
      tonsils, and biomarkers have been proposed as correlates with resistance to
      natural infection. However, the mechanisms used by mycobacteria to manipulate
      host immune response are not fully characterized. Our hypothesis is that the
      immune system proteins under-represented in infected animals, when compared to
      uninfected controls, are used by mycobacteria to guarantee pathogen infection and
      transmission. To address this hypothesis, a comparative proteomics approach was
      used to compare host response between uninfected (TB-) and M. bovis-infected
      young (TB+) and adult animals with different infection status [TB lesions
      localized in the head (TB+) or affecting multiple organs (TB++)]. The results
      identified host immune system proteins that play an important role in host
      response to mycobacteria. Calcium binding protein A9, Heme peroxidase,
      Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under
      represented in TB+ animals when compared to uninfected TB- controls, but protein
      levels were higher as infection progressed in TB++ animals when compared to TB-
      and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+
      adult wild boar when compared to uninfected TB- controls. The results reported
      here suggest that M. bovis manipulates host immune response by reducing the
      production of immune system proteins. However, as infection progresses, wild boar
      immune response recovers to limit pathogen multiplication and promote survival,
      facilitating pathogen transmission. 

PMID- 27027309
TI  - Genetic Determinants of Nipple Aspiration Fluid Yield.
AB  - PURPOSE: Nipple aspiration fluid (NAF) is a non-invasively-acquired biosample
      that can provide a window into the breast environment, but NAF yield is highly
      variable. Its determinants must be better understood for studies of breast cancer
      risk. The wet earwax phenotype was identified as one determinant of NAF yield in
      the 1970s, and is linked to single nucleotide polymorphisms (SNPs) in the ATP
      binding cassette transporter gene ABCC11. We have investigated this, as well as
      SNPs in the prolactin (PRL) and prolactin receptor (PRLR) genes, in relation to
      NAF yield. METHODS: DNA was extracted from white blood cells of 557 NAF yielders
      and 359 non-yielders, and was used to genotype ABCC11 (rs17822931), PRL
      (rs849870, rs849872, rs849886, rs2244502, rs1341239), and PRLR (rs37364,
      rs34024951, rs1610218, rs9292575, rs7718468) using Taqman genotyping assay. The
      association between NAF yield and each single SNP was analyzed using logistic
      regression adjusting for age, race, and menopausal status. RESULTS: ABCC11
      rs17822931 showed a negative association with NAF yield [odds ratio (OR) 0.66, 95
      % confidence interval (CI) 0.49-0.88; p = 0.004]. The PRL rs849870 and the
      haplotype combination with other SNPs showed a marginal association with NAF
      yield. In addition, the years since last birth also showed negative association
      with NAF yielding (OR 0.98, 95 % CI 0.96-0.99; p = 0.001). The combination of the
      years since last birth with ABCC11 SNP revealed significant interaction between
      reproductive factor and genetic factor. CONCLUSIONS: Our results confirmed the
      association between NAF yield and earwax phenotype through ABCC11 genotype.
      Combined with the recency of last birth, ABCC11 genotype should be considered in
      the design of studies utilizing NAF as a biosample.

PMID- 27027310
TI  - Intrathoracic Chemoperfusion Decreases Recurrences in Patients with Full
      Thickness Diaphragm Involvement with Mucinous Appendiceal Adenocarcinoma.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      (HIPEC) is the preferred treatment for selected patients with mucinous
      appendiceal adenocarcinoma. Frequently, the hemidiaphragms are infiltrated with
      tumor, requiring partial diaphragm resection (DR) in order to obtain complete
      cytoreduction (CC-0). The clinical significance of diaphragmatic invasion and the
      optimum management to prevent transmission of disease from abdomen to chest is
      largely unknown. METHODS: This was a retrospective review of 78 patients with
      mucinous appendiceal adenocarcinoma undergoing cytoreduction and partial DR at a
      single institution between 2010 and 2014. RESULTS: Partial DR was necessary in 31
      (39.7 %) patients in order to obtain CC-0. DR was not associated with increased
      morbidity or poor survival. Of the 31 patients who had a DR, 26 (83.9 %) were
      treated with thoracoabdominal chemoperfusion. The remaining five (16.1 %)
      patients had the diaphragm closed prior to HIPEC. Thoracoabdominal chemoperfusion
      was not associated with increased 30-day grade III/IV morbidity or respiratory
      complications. Overall, five (20 %) patients with a DR developed thoracic
      recurrence. There were two (8 %) thoracic recurrences in the 26 patients treated
      with thoracic chemoperfusion compared with three (60 %) in the five patients who
      had their diaphragm closed prior to HIPEC (p = 0.002). In univariate analysis
      histology, CC-0 and thoracoabdominal chemoperfusion were associated with thoracic
      disease-free survival; however, none of these were significant on multivariate
      analysis. CONCLUSION: DR is not associated with increased morbidity and should be
      performed, if needed, to obtain a CC-0. Following DR, patients remain at
      significant risk of developing thoracic recurrence. Thoracoabdominal
      chemoperfusion reduces this risk without increasing morbidity.

PMID- 27027311
TI  - The Risk of Contralateral Nonsentinel Metastasis in Patients with Primary Vulvar
      Cancer and Unilaterally Positive Sentinel Node.

PMID- 27027312
TI  - Survival Following Resection of Intra- and Extra-Hepatic Metastases from
      Colorectal Cancer: A Phase II Trial.
AB  - PURPOSE: Metastasectomy for intrahepatic metastases (IHM) from colorectal cancer
      (CRC) provides excellent 5-year overall survival (OS). Presence of extrahepatic
      metastases (EHM) has been a historic contraindication to surgery. Due to improved
      safety of hepatectomy, there is growing interest in multisite metastasectomy for
      IHM and EHM. The objective of this study was to evaluate the results of
      metastasectomy for patients with IHM and EHM from CRC. METHODS: A phase II study
      of metastasectomy for both IHM and EHM from CRC. Eligible patients with any
      number of IHM and up to three EHM foci, resectable with RO intent, were offered
      metastasectomy. Clinical, survival, and quality of life (QoL) data were analyzed
      using standard statistical methods. RESULTS: Twenty-six patients were enrolled
      with a median age of 58 (range 32-84) years; 14/26 (54 %) presented with
      synchronous disease. The lung was the most common EHM site (13/26, 50 %).
      Protocol surgery was completed in 20/26 (77 %), including 12/26 (46 %) planned
      sequential resections. Major morbidity and perioperative mortality were 5/26 (19
      %) and 1/26 (4 %), respectively. The QoL decline appeared to be transient. All
      QoL domains returned to baseline by 1-year posttreatment. The median recurrence
      free survival (RFS) was 5 months by intent-to-treat analysis. The median OS from
      the time of CRC diagnosis and metastasectomy were 50 and 38 months (3-year OS 80
      and 53 %), respectively. CONCLUSIONS: Complete metastasectomy of multisite CRC is
      safe, but disease recurs in the majority of patients. Data suggest that
      aggressive multisite metastasectomy may provide OS benefit for selected patients.

PMID- 27027313
TI  - Predicting EGFR mutation status in lung cancer:Proposal for a scoring model using
      imaging and demographic characteristics.
AB  - OBJECTIVE: To determine if a combination of CT and demographic features can
      predict EGFR mutation status in bronchogenic carcinoma. METHODS: We reviewed
      demographic and CT features for patients with molecular profiling for resected
      non-small cell lung carcinoma. Using multivariate logistic regression, we
      identified features predictive of EGFR mutation. Prognostic factors identified
      from the logistic regression model were then used to build a more practical
      scoring system. RESULTS: A scoring system awarding 5 points for no or minimal
      smoking history, 3 points for tumours with ground glass component, 3 points for
      airbronchograms, 2 points for absence of preoperative evidence of nodal
      enlargement or metastases and 1 point for doubling time of more than a year,
      resulted in an AUROC of 0.861. A total score of at least 8 yielded a specificity
      of 95 %. On multivariate analysis sex was not found to be predictor of EGFR
      status. CONCLUSIONS: A weighted scoring system combining imaging and demographic
      data holds promise as a predictor of EGFR status. Further studies are necessary
      to determine reproducibility in other patient groups. A predictive score may help
      determine which patients would benefit from molecular profiling and may help
      inform treatment decisions when molecular profiling is not possible. KEY POINTS:
      * EGFR mutation-targeted chemotherapy for bronchogenic carcinoma has a high
      success rate. * Mutation testing is not possible in all patients. * EGFR
      associations include subsolid density, slow tumour growth and minimal/no smoking
      history. * Demographic or imaging features alone are weak predictors of EGFR
      status. * A scoring system, using imaging and demographic features, is more
      predictive.

PMID- 27027314
TI  - Relationship between leukoaraiosis, carotid intima-media thickness and intima
      media thickness variability: Preliminary results.
AB  - OBJECTIVE: To assess the relationship between the degree of leukoaraiosis (LA),
      carotid intima-media thickness (IMT) and intima-media thickness variability
      (IMTV). MATERIALS AND METHODS: Sixty-one consecutive patients, who underwent a
      brain MRI examination and a carotid artery ultrasound, were included in this
      retrospective study, which conformed with the Declaration of Helsinki. Written
      informed consent was waived. In each patient, right/left carotid arteries and
      brain hemispheres were assessed using automated software for IMT, IMTV and LA
      volume. RESULTS: The mean hemispheric LA volume was 2,224 mm3 (SD 2,702 mm3) and
      there was no statistically significant difference in LA volume between the right
      and left hemispheres (p value = 0.628). The mean IMT and IMTV values were 0.866
      mm (SD 0.170) and 0.143 mm (SD 0.100), respectively, without significant
      differences between the right and left sides (p values 0.733 and 0.098,
      respectively). The correlation coefficient between IMTV and LA volume was 0.41 (p
      value = 0.0001), and 0.246 (p value = 0.074) between IMT and LA volume.
      CONCLUSIONS: IMTV significantly correlates with LA volume. Further studies are
      warranted to verify whether this parameter can be used clinically as a marker of
      cerebrovascular risk. KEY POINTS: * Intima-media thickness variability (IMTV)
      significantly correlates with leukoaraiosis volume. * IMTV could be used as a
      marker for cerebrovascular risk. * IMTV seems to be a better predictor of
      weighted mean difference than IMT.

PMID- 27027315
TI  - Visualisation of passive middle ear implants by cone beam and multi-detector
      computed tomography: a comparative in vitro study.
AB  - OBJECTIVES: Modern passive middle ear titanium prostheses are filigree
      structures, resulting in poorer depiction on CT compared to prostheses used in
      the past. We compared the visibility of newer prostheses on cone beam CT (CBCT)
      to multi-detector CT (MDCT) with standard and lower dose in vitro, and analysed
      image noise and metal artefacts. METHODS: Six different titanium middle ear
      prostheses (three partial and one total ossicular replacement prostheses, two
      stapes prostheses) were implanted twice in formalin-fixed head specimens-first
      correctly and then with displacement. Imaging was performed using standard CBCT
      and MDCT as well as MDCT with lower dose (36 single imaging investigations).
      Images were analysed with knowledge of the used types of middle ear prostheses,
      but blinded with respect to the positioning in the specific case. RESULTS: On all
      images the type of prostheses and their positions could be clearly recognized.
      Their identifiability including their details was rated as statistically
      significantly higher for all CBCT investigations than for MDCT. MDCT with lower
      dose showed the worst results. No statistical differences were found in image
      noise and metal artefacts. CONCLUSIONS: If available, CBCT should be preferred
      over MDCT in diagnostic evaluation of passive middle ear prostheses. KEY POINTS:
      * Middle ear prostheses became more filigree, leading to poorer visibility on CT.
      * High spatial resolution and paraxial reconstructions are necessary requirements
      for imaging evaluation. * CBCT and MDCT can identify type and positioning of
      titanium prostheses. * Metal artefacts play a minor part in filigree titanium
      prostheses. * Regarding visualisation of prostheses details, cone beam CT aids
      the evaluation.

PMID- 27027316
TI  - Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad
      Spectrum Coronavirus Protease Inhibitor.
AB  - Coronaviruses infect animals and humans causing a wide range of diseases. The
      diversity of coronaviruses in many mammalian species is contributed by relatively
      high mutation and recombination rates during replication. This dynamic nature of
      coronaviruses may facilitate cross-species transmission and shifts in tissue or
      cell tropism in a host, resulting in substantial change in virulence. Feline
      enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a
      highly fatal disease, called feline infectious peritonitis (FIP), can arise
      through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is
      intimately associated with immune responses and involves depletion of T cells,
      features shared by some other coronaviruses like Severe Acute Respiratory
      Syndrome Coronavirus. The increasing risks of highly virulent coronavirus
      infections in humans or animals call for effective antiviral drugs, but no such
      measures are yet available. Previously, we have reported the inhibitors that
      target 3C-like protease (3CLpro) with broad-spectrum activity against important
      human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of
      our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal
      once certain clinical and laboratory signs become apparent. We found that
      antiviral treatment led to full recovery of cats when treatment was started at a
      stage of disease that would be otherwise fatal if left untreated. Antiviral
      treatment was associated with a rapid improvement in fever, ascites, lymphopenia
      and gross signs of illness and cats returned to normal health within 20 days or
      less of treatment. Significant reduction in viral titers was also observed in
      cats. These results indicate that continuous virus replication is required for
      progression of immune-mediated inflammatory disease of FIP. These findings may
      provide important insights into devising therapeutic strategies and selection of
      antiviral compounds for further development for important coronaviruses in
      animals and humans. 

PMID- 27027317
TI  - The Need for Social Ethics in Interdisciplinary Environmental Science Graduate
      Programs: Results from a Nation-Wide Survey in the United States.
AB  - Professionals in environmental fields engage with complex problems that involve
      stakeholders with different values, different forms of knowledge, and contentious
      decisions. There is increasing recognition of the need to train graduate students
      in interdisciplinary environmental science programs (IESPs) in these issues,
      which we refer to as "social ethics." A literature review revealed topics and
      skills that should be included in such training, as well as potential challenges
      and barriers. From this review, we developed an online survey, which we
      administered to faculty from 81 United States colleges and universities offering
      IESPs (480 surveys were completed). Respondents overwhelmingly agreed that IESPs
      should address values in applying science to policy and management decisions.
      They also agreed that programs should engage students with issues related to
      norms of scientific practice. Agreement was slightly less strong that IESPs
      should train students in skills related to managing value conflicts among
      different stakeholders. The primary challenges to incorporating social ethics
      into the curriculum were related to the lack of materials and expertise for
      delivery, though challenges such as ethics being marginalized in relation to
      environmental science content were also prominent. Challenges related to
      students' interest in ethics were considered less problematic. Respondents
      believed that social ethics are most effectively delivered when incorporated into
      existing courses, and they preferred case studies or problem-based learning for
      delivery. Student competence is generally not assessed, and respondents
      recognized a need for both curricular materials and assessment tools.

PMID- 27027318
TI  - Editorial: Mathematical modelling of infectious diseases.
AB  - The field of disease ecology - the study of the spread and impact of parasites
      and pathogens within their host populations and communities - has a long history
      of using mathematical models. Dating back over 100 years, researchers have used
      mathematics to describe the spread of disease-causing agents, understand the
      relationship between host density and transmission and plan control strategies.
      The use of mathematical modelling in disease ecology exploded in the late 1970s
      and early 1980s through the work of Anderson and May (Anderson and May, 1978,
      1981, 1992; May and Anderson, 1978), who developed the fundamental frameworks for
      studying microparasite (e.g. viruses, bacteria and protozoa) and macroparasite
      (e.g. helminth) dynamics, emphasizing the importance of understanding features
      such as the parasite's basic reproduction number (R 0) and critical community
      size that form the basis of disease ecology research to this day. Since the
      initial models of disease population dynamics, which primarily focused on human
      diseases, theoretical disease research has expanded hugely to encompass livestock
      and wildlife disease systems, and also to explore evolutionary questions such as
      the evolution of parasite virulence or drug resistance. More recently there have
      been efforts to broaden the field still further, to move beyond the standard 'one
      host-one-parasite' paradigm of the original models, to incorporate many aspects
      of complexity of natural systems, including multiple potential host species and
      interactions among multiple parasite species.

PMID- 27027319
TI  - Theoretical Study on Charge Transport Properties of Intra- and Extra-Ring
      Substituted Pentacene Derivatives.
AB  - A series of pentacene derivatives, halogen-substituted and thiophene- and
      pyridine-substituted, have been studied with a focus on the electronic properties
      and charge transport properties using density functional theory and classical
      Marcus charge-transfer theory. The transport properties of holes and electrons
      have been studied to get insight into the effect of halogenation and heteroatom
      substitution on transport and injection of charge carriers. The calculation
      results revealed that fluorination and chlorination can effectively lower the
      lowest unoccupied molecular orbital (LUMO) level, modulate the hole and electron
      reorganization energy, improve the stacking mode of the crystal structure, and
      enhance the ambipolar characteristic. Chlorination gives a better ambipolar
      characteristic. On the basis of halogen substitution, the substitution of
      terminal benzene ring of triisopropyl-silylethynyl-pentacene (TIPS-PEN) by a
      thiophene or pyridine will greatly lower the LUMO level and improve the stacking
      mode, leading to more suitable ambipolar materials. Hence, both intra- and extra
      ring substitution are favorable to enhance the ambipolar transport property of
      TIPS-PEN. 

PMID- 27027320
TI  - Utility of positron emission tomography-magnetic resonance imaging in
      musculoskeletal imaging.
AB  - Differentiation between neoplastic and nonneoplastic conditions magnetic
      resonance imaging (MRI) has established itself as one of the key clinical tools
      in evaluation of musculoskeletal pathology. However, MRI still has several key
      limitations which require supplemental information from additional modalities to
      complete evaluation of various disorders. This has led to the development hybrid
      positron emission tomography (PET)-MRI which is rapidly evolving to address key
      clinical questions by using the morphological strengths of MRI and functional
      information of PET imaging. In this article, we aim to review physical principles
      and techniques of PET-MRI and discuss clinical utility of functional information
      obtained from PET imaging and structural information obtained from MRI imaging
      for the evaluation of musculoskeletal pathology. More specifically, this review
      highlights the role of PET-MRI in musculoskeletal oncology including initial
      diagnosis and staging, treatment planning and post-treatment follow-up. Also we
      will review utility of PET-MRI in evaluating musculoskeletal infections
      (especially in the immunocompromised and diabetics) and inflammatory condition.
      Additionally, common pitfalls of PET-MRI will be addressed. 

PMID- 27027321
TI  - Chiral-Linkage-Induced Hierarchical Ordering of Colloidal Achiral Nanotubes in
      their Thixotropic Gel.
AB  - Macroscopic continuous hierarchical ordering of achiral nanotube "imogolite" was
      achieved by thixotropic gelation of imogolite with chiral hydroxy acid and their
      flow-orienting/subsequent standing for uniaxial alignments of imogolite. The
      chirality change of the hydroxy acids resulted in an inversion of the helical
      ordering. The study presented here first exhibits the millimeter-scale
      supramolecular chirality induced by angstrom-scale molecular handedness in the
      architecture of nanotubes. 

PMID- 27027322
TI  - Functional Characterization of Exonic Variants of the PPARGC1B Gene in
      Coregulation of Estrogen Receptor Alpha.
AB  - Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is
      a coactivator of estrogen receptor (ER)alpha and ERbeta. We previously
      demonstrated a significant association between a variant of exon 5 of the
      PPARGC1B gene (+102525 G>A, R265Q) and airway hyperreactivity (AHR). The aims of
      the study were to evaluate the genetic effects of variants of the PPARGC1B gene
      on the function of ERs. PPARGC1B +102525G and A gene constructs were generated
      using PCR and cloned into a pCMV4 promoter vector. A luciferase reporter assay
      was undertaken in 293T cells cotransfected with one of the PPARGC1B +102525G>A
      constructs, ERalpha, and an estrogen response element (ERE) containing a
      luciferase construct after treatment with 17beta-estradiol. According to the
      luciferase reporter assay, the +102525A allele showed higher ERalpha activity
      than the +102525G allele in response to stimulation with 17beta-estradiol. In
      addition, the interaction between ERalpha and PPARGC1B was evaluated by
      coprecipitation assay. Human influenza hemagglutinin-tagged PPARGC1B
      coprecipitated more intensely with ERalpha in the +102525A than the +102525G
      construct after 17beta estradiol treatment. The variant +102525A allele enhances
      the activity of ERalpha to a greater degree than the +102525G allele of PPARGC1B.

PMID- 27027324
TI  - Effects of cigarette smoke, cessation and switching to a candidate modified risk
      tobacco product on the liver in Apoe -/- mice--a systems toxicology analysis.
AB  - The liver is one of the most important organs involved in elimination of
      xenobiotic and potentially toxic substances. Cigarette smoke (CS) contains more
      than 7000 chemicals, including those that exert biological effects and cause
      smoking-related diseases. Though CS is not directly hepatotoxic, a growing body
      of evidence suggests that it may exacerbate pre-existing chronic liver disease.
      In this study, we integrated toxicological endpoints with molecular measurements
      and computational analyses to investigate effects of exposures on the livers of
      Apoe(-/- )mice. Mice were exposed to 3R4F reference CS, to an aerosol from the
      Tobacco Heating System (THS) 2.2, a candidate modified risk tobacco product
      (MRTP) or to filtered air (Sham) for up to 8 months. THS2.2 takes advantage of a
      "heat-not-burn" technology that, by heating tobacco, avoids pyrogenesis and
      pyrosynthesis. After CS exposure for 2 months, some groups were either switched
      to the MRTP or filtered air. While no group showed clear signs of hepatotoxicity,
      integrative analysis of proteomics and transcriptomics data showed a CS-dependent
      impairment of specific biological networks. These networks included lipid and
      xenobiotic metabolism and iron homeostasis that likely contributed
      synergistically to exacerbating oxidative stress. In contrast, most proteomic and
      transcriptomic changes were lower in mice exposed to THS2.2 and in the cessation
      and switching groups compared to the CS group. Our findings elucidate the complex
      biological responses of the liver to CS exposure. Furthermore, they provide
      evidence that THS2.2 aerosol has reduced biological effects, as compared with CS,
      on the livers of Apoe(-/- )mice. 

PMID- 27027323
TI  - Age and education-matched cut-off scores for the revised German/Swiss-German
      version of ECAS.
AB  - The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has been developed to
      assess cognition and behaviour in patients with amyotrophic lateral sclerosis
      (ALS). Cognitive impairments of ALS-specific and ALS-non-specific functions can
      be determined using cut-off scores based on performance of healthy subjects.
      However, detailed analyses show that older healthy subjects perform worse than
      younger ones, whereas highly-educated individuals perform better than those with
      lower education levels. As a consequence, this study presents new age and
      education matched cut-off scores for the revised German/Swiss-German version of
      the ECAS based on the performance of 86 healthy subjects.

PMID- 27027325
TI  - What is the evidence for managing tone in young children with, or at risk of
      developing, cerebral palsy: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: To conduct a systematic review of the evidence for the
      management of tone in infants 0-24 months of age, with or at risk of developing
      cerebral palsy. METHOD: This review was conducted and reported following the
      Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement. The
      Cochrane Central Register of Controlled Trials, Embase, MEDLINE, CINAHL Plus and
      PsycINFO databases were systematically searched for relevant articles. Inclusion
      criteria were: children aged 0-24 months, identified as at risk of, or having
      cerebral palsy; >=25% of participants <=24 months, and included a standardized
      assessment of tone. Only peer reviewed journal articles were considered. Eligible
      studies were coded using the Oxford Levels of Evidence. Methodological quality
      was assessed using the PEDro scale for randomized controlled trials and the
      checklist for assessing the quality of quantitative studies of Kmet, Cook and Lee
      for non-randomized control trials. RESULTS: A total of 4838 studies were
      identified. After removing duplicates and unrelated studies, a total of 56 full
      text studies were reviewed. A total of five studies met inclusion criteria, two
      of which were RCTs, two pre-/post-test designs and one retrospective case audit.
      Interventions included BoNT-A, Oral Baclofen, Neurofacilitation of Developmental
      Reaction and Neurodevelopmental Therapy. The quality of evidence ranged from
      limited to moderate. CONCLUSION: The management of tone in infants and young
      children is not well described, with a dearth of high-level evidence to support
      intervention in the 0-24 month age-range. This is in contrast to a recent review
      completed by Novak et al. (2013) who report high levels of evidence of
      interventions for children with cerebral palsy, over 2 years of age. Implications
      for Rehabilitation High level of evidence to support clinical decision making for
      the management of tone in young children 0-24 months is not available. The lack
      of available evidence in the management of tone of young children underpins
      service delivery and intervention and impacts on patient outcomes. In the absence
      of clear research evidence, the systematic application of sensitive outcome
      measures is required to confirm treatment effects and generate new evidence.
      Hypertonia should not be managed in isolation. Consideration needs to be given to
      all components of the ICF-CY.

PMID- 27027327
TI  - "Omics" of Selenium Biology: A Prospective Study of Plasma Proteome Network
      Before and After Selenized-Yeast Supplementation in Healthy Men.
AB  - Low selenium levels have been linked to a higher incidence of cancer and other
      diseases, including Keshan, Chagas, and Kashin-Beck, and insulin resistance.
      Additionally, muscle and cardiovascular disorders, immune dysfunction, cancer,
      neurological disorders, and endocrine function have been associated with
      mutations in genes encoding for selenoproteins. Selenium biology is complex, and
      a systems biology approach to study global metabolomics, genomics, and/or
      proteomics may provide important clues to examining selenium-responsive markers
      in circulation. In the current investigation, we applied a global proteomics
      approach on plasma samples collected from a previously conducted, double-blinded
      placebo controlled clinical study, where men were supplemented with selenized
      yeast (Se-Yeast; 300 MUg/day, 3.8 MUmol/day) or placebo-yeast for 48 weeks.
      Proteomic analysis was performed by iTRAQ on 8 plasma samples from each arm at
      baseline and 48 weeks. A total of 161 plasma proteins were identified in both
      arms. Twenty-two proteins were significantly altered following Se-Yeast
      supplementation and thirteen proteins were significantly changed after placebo
      yeast supplementation in healthy men. The differentially expressed proteins were
      involved in complement and coagulation pathways, immune functions, lipid
      metabolism, and insulin resistance. Reconstruction and analysis of protein
      protein interaction network around selected proteins revealed several hub
      proteins. One of the interactions suggested by our analysis, PHLD-APOA4, which is
      involved in insulin resistance, was subsequently validated by Western blot
      analysis. Our systems approach illustrates a viable platform for investigating
      responsive proteomic profile in 'before and after' condition following Se-Yeast
      supplementation. The nature of proteins identified suggests that selenium may
      play an important role in complement and coagulation pathways, and insulin
      resistance. 

PMID- 27027328
TI  - Risk Factors for Surgical Site Infection after Laparoscopic Surgery for Colon
      Cancer.
AB  - BACKGROUND: Surgical site infection (SSI) occurring as a complication after
      laparoscopic surgery for colon cancer causes patients pain and psychological
      stress, prolongs the hospital stay, and increases healthcare costs. The present
      study was designed to clarify the incidence of, and risk factors for, SSI after
      surgery for colon cancer. METHODS: The study group comprised 670 patients (370
      male and 300 female; mean age, 67 y) who underwent laparoscopic surgery for colon
      cancer in our hospital from January 2010 through April 2015. Univariate and
      multivariable analyses were performed for 13 risk factors potentially related to
      post-operative SSI, including gender, age, body mass index, diabetes mellitus,
      American Society of Anesthesiologists (ASA) score, tumor location, pre-operative
      hemoglobin concentration, pre-operative serum albumin concentration, operation
      time, bleeding volume, tumor diameter, pathological stage, and type of sutures
      used for surgical site closure. RESULTS: Surgical site infection occurred in 27
      (4%) of the 670 patients. There was no surgery-related death. Univariate analysis
      of risk factors for SSI showed that the incidence of SSI was substantially lower
      in patients in whom Triclosan-coated PDS Plus((r)) sutures were used for surgical
      site closure (1.8%, seven of 382 patients) than in those in whom Triclosan
      uncoated PDS-II(TM) sutures were used (6.9%, 20 of 288 patients; p = 0.0017). The
      incidence of SSI was substantially greater in patients who had diabetes mellitus
      (9.3%, seven of 75 patients) than in those who did not (3.4%, 20 of 595 patients;
      p = 0.0154). On multivariable analysis, only the non-use of triclosan-coated PDS
      Plus sutures was substantially related to SSI, with an odds ratio of 3.322 (p =
      0.021) as compared with the use of triclosan-coated PDS Plus sutures.
      CONCLUSIONS: To prevent SSI after laparoscopic surgery for colon cancer,
      triclosan-coated PDS Plus sutures should be used for abdominal closure.

PMID- 27027326
TI  - Endothelial Mechanosignaling: Does One Sensor Fit All?
AB  - SIGNIFICANCE: Forces are important in the cardiovascular system, acting as
      regulators of vascular physiology and pathology. Residing at the blood vessel
      interface, cells (endothelial cell, EC) are constantly exposed to vascular
      forces, including shear stress. Shear stress is the frictional force exerted by
      blood flow, and its patterns differ based on vessel geometry and type. These
      patterns range from uniform laminar flow to nonuniform disturbed flow. Although
      ECs sense and differentially respond to flow patterns unique to their
      microenvironment, the mechanisms underlying endothelial mechanosensing remain
      incompletely understood. RECENT ADVANCES: A large body of work suggests that ECs
      possess many mechanosensors that decorate their apical, junctional, and basal
      surfaces. These potential mechanosensors sense blood flow, translating physical
      force into biochemical signaling events. CRITICAL ISSUES: Understanding the
      mechanisms by which proposed mechanosensors sense and respond to shear stress
      requires an integrative approach. It is also critical to understand the role of
      these mechanosensors not only during embryonic development but also in the
      different vascular beds in the adult. Possible cross talk and integration of
      mechanosensing via the various mechanosensors remain a challenge. FUTURE
      DIRECTIONS: Determination of the hierarchy of endothelial mechanosensors is
      critical for future work, as is determination of the extent to which
      mechanosensors work together to achieve force-dependent signaling. The role and
      primary sensors of shear stress during development also remain an open question.
      Finally, integrative approaches must be used to determine absolute mechanosensory
      function of potential mechanosensors. Antioxid. Redox Signal. 25, 373-388.

PMID- 27027329
TI  - From cost to value in medical education.

PMID- 27027330
TI  - Placebo Response in Pediatric Anxiety Disorders: Implications for Clinical Trial
      Design and Interpretation.
AB  - OBJECTIVES: The characterization and prediction of placebo response in clinical
      trials of youth with anxiety disorders have received little attention, despite
      the critical effects of placebo response rate on the success or failure of
      clinical trials. With this in mind, we sought to examine the factors that predict
      or influence placebo response in randomized controlled trials of youth with
      anxiety disorders. METHODS: Prospective, randomized, parallel-group controlled
      trials of psychopharmacologic interventions in pediatric patients with anxiety
      disorders were identified using a search of PubMed/Medline (1966-2015). Weighted
      least squares regression models and z-tests were utilized to examine the impact
      of continuous and categorical variables, respectively, on placebo response. These
      variables included demographic (e.g., age, percent white, percent female),
      clinical (e.g., baseline symptom severity), and trial characteristics (sample
      size, duration, funding). Finally, the relationship between the class of
      comparator medication and placebo response rate was examined using a multiple
      comparison for proportions test. RESULTS: The analyses of data from 14 trials
      involving 2230 patients and 9 medications reveal that higher placebo response
      rates were associated with a greater number of study sites (p = 0.013) and fewer
      patients per site (p < 0.008), while placebo dropout rates increased with more
      recent publication (p = 0.01) and were positively associated with the number of
      study visits (p < 0.02). Lower placebo response rates were associated with
      federally funded studies (z = -4.61, p < 0.001), studies conducted in the United
      States (z = 1.81, p < 0.035), and with an increased likelihood of detecting a
      significant effect on the primary outcome (z = 4.58, p < 0.0001). Additionally,
      studies, in which the majority of patients (>60%) had a diagnosis of social
      anxiety disorder, exhibited lower placebo response rates (p < 0.001). Finally,
      for trials, effect size has decreased over time (p = 0.004). CONCLUSIONS:
      Important trial-specific factors affect placebo response and placebo dropout in
      youth with anxiety disorders and have pragmatic implications for the conduct and
      design of clinical trials and raise the possibility that limiting the number of
      sites while maximizing the number of patients per site could enhance the ability
      to detect medication-placebo differences.

PMID- 27027331
TI  - Urinary dialkylphosphate metabolites and health symptoms among farmers in
      Thailand.
AB  - Using a cross-sectional study, we investigated urinary DAPs levels and health
      symptoms related to the type of crop cultivation and farm tasks among 84 farmers
      in Phayao Province of northern Thailand. The results showed that the average of
      ?DAPs levels was 10.93 +/- 19.64 MUg/g creatinine (range 1.48-163.90 MUg/g
      creatinine). The compound found the most was DEP, followed by DETP, DEDTP, DMP,
      DMTP, and DMDTP, respectively. The type of crop cultivation may be associated
      with an increasing prevalence of respiratory tract, muscle system, and skin
      irritation. Farm tasks were associated with an increasing prevalence of muscle
      system and skin irritation. It was difficult to assess adverse health symptoms
      associated with urinary DAPs in low levels of exposure; therefore, further
      investigation is needed using more sensitive biomarkers and more sensitive health
      symptom measurement.

PMID- 27027332
TI  - A new method to assess the deformations of internal organs of the abdomen during
      impact.
AB  - OBJECTIVES: Due to limitations of classic imaging approaches, the internal
      response of abdominal organs is difficult to observe during an impact. Within the
      context of impact biomechanics for the protection of the occupant of transports,
      this could be an issue for human model validation and injury prediction. METHODS:
      In the current study, a previously developed technique (ultrafast ultrasound
      imaging) was used as the basis to develop a protocol to observe the internal
      response of abdominal organs in situ at high imaging rates. The protocol was
      applied to 3 postmortem human surrogates to observe the liver and the colon
      during impacts delivered to the abdomen. RESULTS: The results show the
      sensitivity of the liver motion to the impact location. Compression of the colon
      was also quantified and compared to the abdominal compression. CONCLUSIONS: These
      results illustrate the feasibility of the approach. Further tests and comparisons
      with simulations are under preparation.

PMID- 27027333
TI  - Analysis of subsequent surgery rates among endometriosis patients who underwent
      surgery with and without concomitant leuprolide acetate therapy.
AB  - Objective To compare subsequent endometriosis-related surgery following initial
      laparoscopy among women treated with leuprolide acetate (LA) or other
      endometriosis therapies versus women who received no pharmacotherapy. Research
      design and methods This retrospective cohort analysis utilized MarketScan
      Commercial claims data. Women with endometriosis aged 18-49 who underwent
      laparoscopy between 1 January 2005 and 31 December 2011 were identified using
      diagnosis and procedures codes and were categorized into four cohorts based on
      claims within 90 days of laparoscopy: surgery plus adherent LA, surgery plus non
      adherent LA, surgery plus other therapy, and surgery alone. Patients with
      proportion of days covered >=0.80 in the 6 months after laparoscopy were
      considered adherent to LA. Main outcome measures Subsequent endometriosis-related
      surgery (laparoscopy, laparotomy or other excision/ablation/fulguration of
      endometriosis lesions, oophorectomy, or hysterectomy) was measured in the 6 and
      12 months following initial laparoscopy. Risk of subsequent surgery was compared
      using multivariable Cox proportional hazards modeling. Results Most women were
      treated with surgery only (n = 9865); fewer were treated with LA (adherent: n =
      202; non-adherent: n = 490) or other therapies (n = 230). The proportion of
      patients with subsequent surgery ranged from 2.0% to 10.0% during the 6 month
      follow-up (12 month: 9.7% to 13.5%). Adherent LA use was associated with
      significantly lower risk of surgery compared to surgery alone (hazard ratio [HR]
      = 0.31, p = 0.020) while use of other therapies was associated with significantly
      higher risk (HR = 1.51, p = 0.045) over the 6 month follow-up. There was no
      significant difference between the surgery plus non-adherent LA and surgery only
      cohort over 6 months (p = 0.247). The association between adherent LA and
      subsequent surgery was not significant over the 12 month follow-up. Conclusion
      Therapy with LA after laparoscopy for endometriosis was associated with lower
      risk of subsequent surgery at 6 months among women who were adherent to LA. Key
      limitations include lack of ability to capture disease severity which may have
      resulted in uncontrolled confounding.

PMID- 27027334
TI  - Postoperative versus Spontaneous Intracranial Abscess: Diagnostic Value of the
      Apparent Diffusion Coefficient for Accurate Assessment.
AB  - Purpose To assess the diagnostic value of apparent diffusion coefficients (ADCs)
      in spontaneous intracranial abscesses compared with those occurring after primary
      neurosurgery. Materials and Methods This retrospective comparative study was
      approved by the local institutional review board. The requirement to obtain
      written informed consent was waived. A total of 73 consecutive patients who
      underwent preoperative diffusion-weighted magnetic resonance (MR) imaging from
      February 2005 to May 2015 were divided into two cohorts depending on whether the
      abscess was identified after a primary neurosurgical procedure (n = 43) or was a
      spontaneous abscess (n = 30). Abscesses were assessed for ADC by two readers
      independently. ADCs were described as medians with interquartile range. The Mann
      Whitney and chi(2) tests were used to compare ADCs between the two cohorts, and
      chi(2) automatic interaction detection analysis was used to classify the ADCs
      into categories according to the cohorts. Results The median ADC of postoperative
      abscesses was 1.34 * 10(-3) mm(2)/sec (interquartile range, 1.00-1.62 * 10(-3)
      mm(2)/sec), which was significantly higher than the median ADC of spontaneous
      abscesses, 0.68 * 10(-3) mm(2)/sec (interquartile range, 0.58-0.79 * 10(-3)
      mm(2)/sec; P < .001). Twenty four (83%) of the abscesses with ADCs less than 0.79
      * 10(-3) mm(2)/sec were found to be spontaneous, while only six (27%) abscesses
      with ADCs between 0.79 and 1.33 * 10(-3) mm(2)/sec and no abscesses with ADCs
      greater than 1.33 * 10(-3) mm(2)/sec were spontaneous (P < .001). Conclusion
      Significantly higher ADCs were found in postoperative abscesses compared with
      those in spontaneous abscesses. Diffusion-weighted imaging with ADC mapping is
      not sufficient for excluding postoperative intracranial abscess and should not be
      used as the key diagnostic modality in this situation. ((c)) RSNA, 2016. 

PMID- 27027336
TI  - Laparoscopy for Rectal Cancer: Is the Story Settled?

PMID- 27027335
TI  - Validation of Software Gating: A Practical Technology for Respiratory Motion
      Correction in PET.
AB  - Purpose To assess the performance of hardware- and software-gating technologies
      in terms of qualitative and quantitative characteristics of respiratory motion in
      positron emission tomography (PET) imaging. Materials and Methods Between 2010
      and 2013, 219 fluorine 18 fluorodeoxyglucose PET examinations were performed in
      116 patients for assessment of pulmonary nodules. All patients provided informed
      consent in this institutional review board-approved study. Acquisitions were
      reconstructed as respiratory-gated images by using hardware-derived respiratory
      triggers and software-derived signal (via an automated postprocessing method).
      Asymmetry was evaluated in the joint distribution of reader preference, and
      linear mixed models were used to evaluate differences in outcomes according to
      gating type. Results In blind reviews of reconstructed gated images, software was
      selected as superior 16.9% of the time (111 of 657 image sets; 95% confidence
      interval [CI]: 14.0%, 19.8%), and hardware was selected as superior 6.2% of the
      time (41 of 657 image sets; 95% CI: 4.4%, 8.1%). Of the image sets, 76.9% (505 of
      657; 95% CI: 73.6%, 80.1%) were judged as having indistinguishable motion
      quality. Quantitative analysis demonstrated that the two gating strategies
      exhibited similar performance, and the performance of both was significantly
      different from that of nongated images. The mean increase +/- standard deviation
      in lesion maximum standardized uptake value was 42.2% +/- 38.9 between nongated
      and software-gated images, and lesion full width at half maximum values decreased
      by 9.9% +/- 9.6. Conclusion Compared with vendor-supplied respiratory-gating
      hardware methods, software gating performed favorably, both qualitatively and
      quantitatively. Fully automated gating is a feasible approach to motion
      correction of PET images. ((c)) RSNA, 2016 Online supplemental material is
      available for this article.

PMID- 27027337
TI  - Secure Messaging in Electronic Health Records and Its Impact on Diabetes Clinical
      Outcomes: A Systematic Review.
AB  - In 2009, President Barack Obama signed into law the Health Information Technology
      for Economic and Clinical Health (HITECH) Act, which aims for the universal
      adoption of electronic health records (EHRs) in primary care settings and
      "meaningful use" of this technology. The objectives of "meaningful use" are well
      defined and executed in stages; one of the objectives of stage 2, beginning in
      2014, was implementation of a secure messaging system between patients and
      providers. Secure messaging has been shown to positively affect patients who
      struggle with managing chronic diseases on a day to day basis. This review aims
      to assess the clinical evidence supporting the use of secure messaging in EHRs in
      self-management of diabetes. METHODS: A systematic search of PubMed was
      conducted, and 320 results were returned. Of these, 11 were selected based on
      outlined criteria. CONCLUSIONS: Evidence from 7 of the 11 included studies
      suggests significant improvement in patients' hemoglobin A1c (HbA1c) with the use
      of secure messaging. However, improvements in patients' secondary outcomes, such
      as blood pressure and cholesterol, were inconsistent. Further work must be done
      to determine how to best maximize the potential of available tools such as secure
      messaging and EHRs to improve patient outcomes.

PMID- 27027338
TI  - Relative Inhibitions of 5-Lipoxygenase and Myeloperoxidase and Free-Radical
      Scavenging Activities of Daidzein, Dihydrodaidzein, and Equol.
AB  - The effects of bioavailability and metabolic transformation on the biological
      activities of daidzein are relatively unknown. The effects of daidzein,
      dihydrodaidzein, and equol at physiologically relevant concentrations on the
      production of leukotriene B4 and F2-isoprostanes, and myeloperoxidase enzyme
      activity in freshly isolated human neutrophils were examined. Equol, at
      physiological concentrations, inhibited leukotriene B4 production (IC50-200
      nmol/L) in human neutrophils significantly more than daidzein and dihydrodaidzein
      (IC50 values >1000 nmol/L). Daidzein, dihydrodaidzein, and equol did not affect
      the enzymatic hydrolysis of leukotriene A4 to leukotriene B4, suggesting that
      they exerted their inhibitory effects on the 5-lipoxygenase activity. Daidzein
      (IC50 = 600 nmol/L) protected against free radical peroxidation of arachidonic
      acid significantly more than did equol and dihydrodaidzein (IC50 values >1000
      nmol/L). Equol also showed significantly greater inhibition of myeloperoxidase
      activity (IC50 = 450 nmol/L) when compared to daidzein and dihydrodaidzein. Equol
      accumulated within the human neutrophils at significantly higher concentrations
      than daidzein and dihydrodaidzein after incubation with the three compounds at
      physiologically relevant concentrations. Neutrophils were able to accumulate
      intracellular daidzein, dihydrodaidzein, and equol up to a concentration of ~600
      nmol/L. Our results provide in vitro evidence that the biological activities of
      daidzein are profoundly influenced by bioavailability and metabolic
      transformation. 

PMID- 27027339
TI  - Associations between serum CA724 and HER2 overexpression among stage II-III
      resectable gastric cancer patients: an observational study.
AB  - OBJECTIVES: Associations between serum tumor biomarkers and human epidermal
      growth factor receptor 2 (HER2) overexpression among locally advanced gastric
      cancer patients were yet to be determined and therefore warranted investigation.
      RESULTS: A total of 318 patients were analyzed. The odds ratios of CA724 were
      4.79 (95% CI 1.55-14.79) and 6.29 (1.40-28.19) in comparing the HER2 (2+/3+) and
      HER2 (3+) with the negative group, respectively (p < 0.05). A combination of the
      four biomarkers yielded slightly but not significantly greater areas under the
      curve (AUC = 0.83; 0.71-0.94) than that of serum CA724 alone (0.80; 0.68-0.91);
      however, an index generated from the combination had better diagnostic
      performance with 85.7% sensitivity, 80.4% specificity and 97.8% negative
      predictive value to predict the strong overexpression of HER2 (3+). CA199, CEA or
      CA125 alone was not associated with HER2 overexpression. Leave-one-out cross
      validation found a consistent association between serum CA724 and HER2 (2+/3+)
      overexpression. METHODS: Patients undergoing radical gastrectomy from 8/2012 to
      12/2013 and with pathological stage II-III gastric cancer were retrospectively
      analyzed. HER2 expression of the surgical samples was estimated using
      immunohistochemistry; serum CA724, CA199, CEA and CA125 were preoperatively
      tested. Internal validation was performed using the leave-one-out approach.
      CONCLUSIONS: Serum CA724 is significantly associated with the overexpression of
      HER2 among locally advanced gastric cancer patients. The combination of CA724,
      CA199, CEA and CA125 is better than serum CA724 alone in predicting HER2
      overexpression. External validation and further investigation of the biological
      mechanisms of these associations are required.

PMID- 27027340
TI  - Inhibition of autophagy potentiates anticancer property of 20(S)-ginsenoside Rh2
      by promoting mitochondria-dependent apoptosis in human acute lymphoblastic
      leukaemia cells.
AB  - Acute lymphoblastic leukaemia (ALL) is the most prevalent childhood malignancy.
      Although most children with ALL are cured, there is still a group of patients for
      which therapy fails owing to severe toxicities and drug resistance. Ginsenoside
      Rh2 (GRh2), a major bioactive component isolated from Panax ginseng, has been
      shown to have a therapeutic effect on some tumors. However, the molecular
      mechanisms of cell death induced by 20(S)-GRh2 in ALL cells remains unclear. In
      this study, we showed that 20(S)-GRh2 inhibited the cell growth and induced
      mitochondria-dependent apoptosis and autophagy. But it has no cytotoxic effect on
      human normal blood cells. Furthermore, autophagy plays a protective role in 20(S)
      GRh2-induced apoptosis in ALL cell lines and human primary ALL cells. We
      demonstrated that either genetic or pharmacologic inhibition of autophagy could
      be more effective in reducing viability and enhancing 20(S)-GRh2-induced toxicity
      than 20(S)-GRh2 treatment alone. In addition, inhibition of autophagy could
      aggravate mitochondrial ROS generation and mitochondrial damage, and then
      accelerate mitochondria-dependent apoptosis. Taken together, these results
      suggest that inhibition of autophagy can sensitize ALL cells towards 20(S)-GRh2.
      The appropriate inhibition of autophagy could provide a powerful strategy to
      increase the potency of 20(S)-GRh2 as a novel anticancer agent for ALL therapy. 

PMID- 27027341
TI  - HMGA2 overexpression plays a critical role in the progression of esophageal
      squamous carcinoma.
AB  - Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor
      worldwide. However, there is still a lack of deeper knowledge about biological
      alterations involved in ESCC development. High Mobility Group A (HMGA) protein
      family has been related with poor outcome and malignant cell transformation in
      several tumor types. In this way, the aim of this study was to analyze the
      expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial
      cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC
      and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but
      not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by
      the immunohistochemical analysis. Indeed, accordingly to mRNA expression data,
      HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples,
      while it was barely expressed in the respective control. Conversely, HMGA1, but
      not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly,
      HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines,
      suggesting that HMGA2 overexpression is involved in ESCC progression. 

PMID- 27027342
TI  - Risk of recurrence and conditional survival in complete responders treated with
      TKIs plus or less locoregional therapies for metastatic renal cell carcinoma.
AB  - PURPOSE: We retrospectively analyzed the risk of recurrence and conditional
      Disease-Free Survival (cDFS) in 63 patients with complete remission during
      treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in
      metastatic renal cell carcinoma. RESULTS: 37% patients achieve CR with TKI alone,
      while 63% with additional loco-regional treatments. 49% patients recurred after
      CR, with a median Disease free survival of 28.2 months. Patients treated with
      multimodal approaches present lower rate of recurrence (40% vs 61%) and longer
      Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9
      months, p=0.039).Furthermore the rate of recurrence was higher in patients with
      brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued
      TKI therapy after complete response had a longer disease free survival than
      patients who stopped therapy, although the difference was not significant (42.1
      vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal
      treatment and who continued TKIs than the other patient arms. CONCLUSIONS: The
      prognostic value of CR depends on the site where was obtained and how was
      obtained (with or without locoregional treatment). Cessation of TKI should be
      carefully considered in complete responder patients.

PMID- 27027343
TI  - Huaier extract synergizes with tamoxifen to induce autophagy and apoptosis in ER
      positive breast cancer cells.
AB  - Tamoxifen (TAM) is the most widely used endocrine therapy for estrogen receptor
      (ER)-positive breast cancer patients, but side effects and the gradual
      development of insensitivity limit its application. We investigated whether
      Huaier extract, a traditional Chinese medicine, in combination with TAM would
      improve treatment efficacy in ER-positive breast cancers. MTT, colony formation,
      and invasion and migration assays revealed that the combined treatment had
      stronger anticancer effects than either treatment alone. Huaier extract enhanced
      TAM-induced autophagy, apoptosis, and G0/G1 cell cycle arrest, as measured by
      acidic vesicular organelle (AVO) staining, TUNEL, flow cytometry, and western
      blot. Additionally, combined treatment inhibited tumorigenesis and metastasis by
      suppressing the AKT/mTOR signaling pathway. Huaier extract also enhanced the
      inhibitory effects of TAM on tumor growth in vivo in a xenograft mouse model.
      These results show that Huaier extract synergizes with TAM to induce autophagy
      and apoptosis in ER-positive breast cancer cells by suppressing the AKT/mTOR
      pathway. 

PMID- 27027345
TI  - Body mass index and cholesterol level predict surgical outcome in patients with
      hepatocellular carcinoma in Taiwan - a cohort study.
AB  - Curative surgical resection (CSR) remains the most effective therapeutic
      intervention for patients with hepatocellular carcinoma (HCC); however, frequent
      post-surgical recurrence leads to high cancer related mortality. This study aimed
      to clarify the role of body mass index (BMI) and serum cholesterol level in
      predicting post-surgical outcomes in HCC patients after CSR. A total of 484 HCC
      patients including 213 BMIhigh and 271 BMIlow patients were included. Overall
      survival (OS) and recurrence-free survival (RFS) rates were examined in patients
      with differential BMI and serum cholesterol level. The analysis showed that
      significant different 1-, 3- and 5-year cumulative OS rates (P-value=0.015) and
      RFS rate (P-value=0.010) between BMIlow and BMIhigh patients. Further analysis in
      groups with differential serum cholesterol levels among BMIlow and BMIhigh
      patients indicated that the BMIlow/Chollow patients exhibited the significant
      lower cumulative OS and RFS rates in comparison with the remaining subjects (P
      value=0.007 and 0.039 for OS and RFS rates, respectively). In conclusion, the
      coexistence of low BMI and low serum cholesterol level could serve as prognostic
      factors to predict post-operative outcomes in HCC patients undergoing surgical
      hepatectomy. 

PMID- 27027344
TI  - Prediction of mycoplasma hominis proteins targeting in mitochondria and cytoplasm
      of host cells and their implication in prostate cancer etiology.
AB  - Although the idea of bacteria causing different types of cancer has exploded
      about century ago, the potential mechanisms of carcinogenesis is still not well
      established. Many reports showed the involvement of M. hominis in the development
      of prostate cancer, however, mechanistic approach for growth and development of
      prostate cancer has been poorly understood. In the current study, we predicted M.
      hominis proteins targeting in the mitochondria and cytoplasm of host cells and
      their implication in prostate cancer. A total of 77 and 320 proteins from M.
      hominis proteome were predicted to target in the mitochondria and cytoplasm of
      host cells respectively. In particular, various targeted proteins may interfere
      with normal growth behaviour of host cells, thereby altering the decision of
      programmed cell death. Furthermore, we investigated possible mechanisms of the
      mitochondrial and cytoplasmic targeted proteins of M. hominis in etiology of
      prostate cancer by screening the whole proteome.

PMID- 27027346
TI  - Towards understanding the lifespan extension by reduced insulin signaling:
      bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.
AB  - DAF-16, the C. elegans FOXO transcription factor, is an important determinant in
      aging and longevity. In this work, we manually curated FOXODB
      http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208
      genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found
      interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some
      targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets
      are involved in lifespan extension induced by dietary restriction. And (iv) DAF
      16 direct targets might play global roles in lifespan regulation. 

PMID- 27027347
TI  - Novel signaling collaboration between TGF-beta and adaptor protein Crk
      facilitates EMT in human lung cancer.
AB  - The signaling adaptor protein Crk has been shown to play an important role in
      various human cancers. However, its regulatory machinery is not clear. Here, we
      demonstrated that Crk induced EMT in A549 human lung adenocarcinoma cells through
      differential regulation of Rac1/Snail and RhoA/Slug, leading to decreased
      expression of E-cadherin and increased N-cadherin, fibronectin, and MMP2
      expression. Cancer cells with mesenchymal features produced TGF-beta and also
      increased the levels of TGF-beta receptor. TGF-beta increased the endogenous
      levels of Crk and also augmented Crk-dependent expression of Snail and Slug, and
      conversely TGF-beta receptor inhibitor suppressed the levels of Snail and Slug.
      Overexpression of Crk was observed at the invasive front of human lung cancer
      tissues and was significantly associated with poor prognosis. Thus, TGF-beta and
      Crk collaborate to form a positive feedback loop to facilitate EMT, which may
      lead to the malignancy of human cancers possibly being affected by their
      microenvironment. 

PMID- 27027348
TI  - Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for
      cancer chemotherapy.
AB  - Cancer is a disease caused by the abnormal proliferation and differentiation of
      cells governed by tumorigenic factors. Chemotherapy is one of the major cancer
      treatment strategies, and it functions by targeting the physiological
      capabilities of cancer cells, including sustained proliferation and angiogenesis,
      the evasion of programmed cell death, tissue invasion and metastasis. Remarkably,
      natural products have garnered increased attention in the chemotherapy drug
      discovery field because they are biologically friendly and have high therapeutic
      effects. Tetrandrine, isolated from the root of Stephania tetrandra S Moore, is a
      traditional Chinese clinical agent for silicosis, autoimmune disorders,
      inflammatory pulmonary diseases, cardiovascular diseases and hypertension.
      Recently, the novel anti-tumor effects of tetrandrine have been widely
      investigated. More impressive is that tetrandrine affects multiple biological
      activities of cancer cells, including the inhibition of proliferation,
      angiogenesis, migration, and invasion; the induction of apoptosis and autophagy;
      the reversal of multidrug resistance (MDR); and the enhancement of radiation
      sensitization. This review focuses on introducing the latest information about
      the anti-tumor effects of tetrandrine on various cancers and its underlying
      mechanism. Moreover, we discuss the nanoparticle delivery system being developed
      for tetrandrine and the anti-tumor effects of other bisbenzylisoquinoline
      alkaloid derivatives on cancer cells. All current evidence demonstrates that
      tetrandrine is a promising candidate as a cancer chemotherapeutic.

PMID- 27027349
TI  - Anticancer properties of nimbolide and pharmacokinetic considerations to
      accelerate its development.
AB  - Nimbolide is one of the main components in the leaf extract of Azadirachta indica
      (A. indica). Accumulating evidence from various in vitro and in vivo studies
      indicates that nimbolide possesses potent anticancer activity against several
      types of cancer and also shows potential chemopreventive activity in animal
      models. The main mechanisms of action of nimbolide include anti-proliferation,
      induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation
      of carcinogen-metabolizing enzymes. Although multiple pharmacodynamic (PD)
      studies have been carried out, nimbolide is still at the infant stage in the drug
      development pipeline due to the lack of systematic pharmacokinetic (PK) studies
      and long-term toxicological studies. Preclinical PK and toxicological studies are
      vital in determining the dosage range to support the safety of nimbolide for
      first-in-human clinical trials. In this review, we will provide a comprehensive
      summary for the current status of nimbolide as an anticancer and chemopreventive
      lead compound, and highlight the importance of systematic preclinical PK and
      toxicological studies in accelerating the process of application of nimbolide as
      a therapeutic agent against various malignancies.

PMID- 27027350
TI  - Transcriptome-wide analysis of compression-induced microRNA expression alteration
      in breast cancer for mining therapeutic targets.
AB  - Tumor growth-generated mechanical compression may increase or decrease expression
      of microRNAs, leading to tumor progression. However, little is known about
      whether mechanical compression induces aberrant expression of microRNAs in cancer
      and stromal cells. To investigate the relationship between compression and
      microRNA expression, microRNA array analysis was performed with breast cancer
      cell lines and cancer-associated fibroblasts (CAFs) exposed to different
      compressive conditions. In our study, mechanical compression induced alteration
      of microRNA expression level in breast cancer cells and CAFs. The alteration was
      greater in the breast cancer cells than CAFs. Mechanical compression mainly
      induced upregulation of microRNAs rather than downregulation. In a parallel mRNA
      array analysis, more than 25% of downregulated target genes were functionally
      involved in tumor suppression (apoptosis, cell adhesion, and cell cycle arrest),
      whereas generally less than 15% were associated with tumor progression
      (epithelial-mesenchymal transition, migration, invasion, and angiogenesis). Of
      all cells examined, MDA-MB-231 cells showed the largest number of compression
      upregulated microRNAs. miR-4769-5p and miR-4446-3p were upregulated by
      compression in both MDA-MB-231 cells and CAFs. Our results suggest that
      mechanical compression induces changes in microRNA expression level, which
      contribute to tumor progression. In addition, miR-4769-5p and miR-4446-3p may be
      potential therapeutic targets for incurable cancers, such as triple negative
      breast cancer, in that this would reduce or prevent downregulation of tumor
      suppressing genes in both the tumor and its microenvironment simultaneously. 

PMID- 27027351
TI  - Adipose microenvironment promotes triple negative breast cancer cell invasiveness
      and dissemination by producing CCL5.
AB  - Growing evidence indicates that adiposity is associated with raised cancer
      incidence, morbidity and mortality. In a subset of tumors, cancer cell growth
      and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed,
      adipocytes represent the most abundant cell types surrounding breast cancer
      cells. We have studied the mechanisms by which peritumoral human adipose tissue
      contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and
      dissemination.Co-culture with human adipocytes enhanced MDA-MB231 cancer cell
      invasiveness. Adipocytes cultured in high glucose were 2-fold more active in
      promoting cell invasion and motility compared to those cultured in low glucose.
      This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5).
      Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte
      induced breast cancer cell migration and invasion. CCL5 immuno-detection in
      peritumoral adipose tissue of women with TNBC correlated with lymph node (p-value
      = 0.04) and distant metastases (p-value = 0.001). A positive trend was also
      observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves
      showed a negative correlation between CCL5 staining in the peritumoral adipose
      tissue and overall survival of patients (p-value = 0.039).Thus, inhibition of
      CCL5 in adipose microenvironment may represent a novel approach for the therapy
      of highly malignant TNBC. 

PMID- 27027352
TI  - Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation
      via LSD1 interaction and repression of NCALD in non-small-cell lung cancer.
AB  - Despite improvements in diagnostics and treatment of non-small cell lung cancer
      (NSCLC), it remains the leading causes of cancer-related mortality worldwide. In
      more recent years, mutiple lines of evidence have highlighted long noncoding RNAs
      (lncRNAs) serve as novel class of regulators of cancer biological processes,
      including proliferation, apoptosis and metastasis. LncRNAs serve as a novel class
      of regulators of cancer biological processes in cancer, but little is known of
      their expression and potential functions in NSCLC. We identified an oncogene,
      linc00673, whose expression level was upregulated by bioinformatics analyses and
      qRT-PCR analyses in NSCLC. The effects of linc00673 on tumor progression were
      investigated in vitro and in vivo. Linc00673 knockdown significantly inhibited
      cell proliferation and colony-forming ability, and suppressed S-phase entry in
      vitro and shRNA linc00673 mediated knockdown significantly inhibit tumor growth
      in vivo, meanwhile, linc00673 overexpression increased tumor cell growth.
      Analysis of RNAseq data revealed linc00673 could modulate the transcription of a
      large amount of genes including oncogene and tumor suppressor gene, so we
      investigated the role and regulatory mechanism of linc00673 in NSCLC
      proliferation. Further mechanistic analyses indicated that the oncogenic activity
      of linc00673 is partially attributable to its repression of NCALD through
      association with the epigenetic repressor LSD1. Taken together, these findings
      suggested that linc00673 could play crucial role in NSCLC progression and might
      be a potential therapeutic target for patients with NSCLC. 

PMID- 27027353
TI  - Cyclin-dependent kinase 5 stabilizes hypoxia-inducible factor-1alpha: a novel
      approach for inhibiting angiogenesis in hepatocellular carcinoma.
AB  - We recently introduced CDK5 as target in HCC, regulating DNA damage response.
      Based on this and on our previous knowledge about vascular effects of CDK5, we
      investigated the role of CDK5 in angiogenesis in HCC, one of the most
      vascularized tumors. We put a special focus on the transcription factor HIF
      1alpha, a master regulator of tumor angiogenesis.The interaction of CDK5 with HIF
      1alpha was tested by Western blot, PCR, reporter gene assay,
      immunohistochemistry, kinase assay, co-immunoprecipitation, mass spectrometry,
      and mutation studies. In vivo, different murine HCC models, were either induced
      by diethylnitrosamine or subcutaneous injection of HUH7 or HepG2 cells. The
      correlation of vascular density and CDK5 was assessed by immunostaining of a
      microarray of liver tissues from HCC patients.Inhibition of CDK5 in endothelial
      or HCC cells reduced HIF-1alpha levels in vitro and in vivo, and transcription of
      HIF-1alpha target genes (VEGFA, VEGFR1, EphrinA1). Mass spectrometry and site
      directed mutagenesis revealed a stabilizing phosphorylation of HIF-1alpha at
      Ser687 by CDK5. Vascular density was decreased in murine HCC models by CDK5
      inhibition.In conclusion, inhibiting CDK5 is a multi-modal systemic approach to
      treat HCC, hitting angiogenesis, as well as the tumor cells themselves. 

PMID- 27027354
TI  - Poly(ADP-ribose) polymerase 1 inhibition protects cardiomyocytes from
      inflammation and apoptosis in diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy (DCM) is characterized by structural alterations such as
      cardiomyocyte hypertrophy, necrosis and focal fibrosis. Poly(ADP-ribose)
      polymerase 1 (PARP-1) is a nuclear enzyme which can be activated by DNA damage
      and plays a critical role in various diseases. We hypothesized that PARP-1 may
      play an important role in DCM and that its inhibition may protect cardiomyocytes
      from inflammation and apoptosis in DCM. H9c2 cardiomyocytes were treated with
      normal glucose, mannitol or high glucose (HG). Male C57BL/6 mice or PARP-1-/-
      mice were treated with streptozotocin (STZ) by intraperitoneal injection for 5
      consecutive days to induce diabetes. In vitro, HG stimulation induced oxidative
      stress and DNA damage and increased PARP-1 expression and activity. Compared with
      the control, pretreatment with PARP-1 siRNA signii!?cantly reduced HG-induced
      inflammatory response, including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and IL-6 secretion, and intercellular adhesion
      molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) expression. PARP-1
      inhibition reduced HG-induced cardiomyocyte apoptosis through downregulation of
      cleaved caspases and activation of IGF-1R/Akt pathway. In vivo, hyperglycemia
      increased the protein expression of nitrotyrosine and PARP-1 as well as PARP-1
      activity. PARP-1 gene deletion significantly improved cardiac dysfunction and
      reduced inflammatory response and apoptosis. This work demonstrated the critical
      role of PARP-1 in diabetic heart injury, and suggested that PARP-1 inhibition may
      be a feasible strategy for the treatment of DCM.

PMID- 27027355
TI  - 5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17
      cell differentiation.
AB  - While it is well established that treatment of cancer patients with 5
      Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU
      in the modulation of immune cells has not been fully established. We found that
      low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without
      apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase
      (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and
      macrophages. Interestingly, the basal expression of TS varies significantly
      between T helper phenotypes and knockdown of TS significantly impairs TH17 and
      TH1 cell differentiation without affecting the differentiation of either Treg or
      TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis
      development by suppressing TH17 and TH1 cell development in a T cell transfer
      colitis model. Taken together, the results highlight the importance of the anti
      inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1
      immune responses. 

PMID- 27027356
TI  - Mitophagy in TGEV infection counteracts oxidative stress and apoptosis.
AB  - The intestinal epithelial cells contain a large number of mitochondria for
      persisting absorption and barrier function. Selective autophagy of mitochondria
      (mitophagy) plays an important role in the quality control of mitochondria and
      maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a
      porcine enteropathogenic coronavirus which induces malabsorption and lethal
      watery diarrhea in suckling piglets. The role of mitophagy in the pathological
      changes caused by TGEV infection is unclear. Here, we report that TGEV induces
      mitophagy to suppress oxidative stress and apoptosis induced by viral infection
      in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce
      mitochondrial injury, abnormal morphology, complete mitophagy, and without
      obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and
      some antioxidant genes upregulation to suppress oxidative stress induced by viral
      infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis
      after TGEV infection. In addition, we demonstrate for the first time that viral
      nucleocapsid protein (N) is located in mitochondria and mitophagosome during
      virus infection or be expressed alone. Those results provide a novel perspective
      for further improvement of prevention and treatment in TGEV infection. These
      results suggest that TGEV infection induce mitophagy to promote cell survival and
      possibly viral infection. 

PMID- 27027359
TI  - Why Would an Obstetrical Nurse Be Interested in Gerontology?

PMID- 27027358
TI  - Paeonol protects endotoxin-induced acute kidney injury: potential mechanism of
      inhibiting TLR4-NF-kappaB signal pathway.
AB  - STUDY DESIGN AND METHODS: In order to determine the therapeutic effect and
      mechanism of paeonol on acute kidney injury induced by endotoxin, an acute kidney
      injury model was established by intraperitoneal administration of
      lipopolysaccharide in mice in vivo and on LPS-induced dendritic cells in vitro.
      Renal tissues were used for histologic examination. Concentrations of blood urea
      nitrogen and serum creatinine were detected, inflammatory cytokines were
      determined by ELISA. The relative proteins' expression of TLR4-NF-kappaB signal
      pathway was assessed by Western blot, the localization and expression of phospho
      NF-kappaB p65 in kidney was monitored by immunohistochemistry. RESULTS: Treatment
      of paeonol successfully cuts histopathological scores and dilutes the
      concentrations of blood urea nitrogen and serum creatinine as index of renal
      injury severity. In addition, paeonol reduces pro-inflammatory cytokines and
      increases anti-inflammatory cytokines stimulated by LPS in a dose-dependent
      manner. Paeonol also inhibits the expression of phosphorylated NF-kappaB p65,
      IkappaBalpha and IKKbeta, and restrains NF-kappaB p65 DNA-binding activity.
      Paeonol treatment also attenuates the effects of LPS on dendritic cells, with
      significant inhibition of pro-inflammatory cytokines release, then TLR4
      expression and NF-kappaB signal pathway have been suppressed. CONCLUSIONS: These
      results indicated that paeonol has protective effects on endotoxin-induced kidney
      injury. The mechanisms underlying such effects are associated with its
      successfully attenuate inflammatory and suppresses TLR4 and NF-kappaB signal
      pathway. Therefore, paeonol has great potential to be a novel and natural product
      agent for treating AKI or septic-AKI.

PMID- 27027357
TI  - Necrostatin-1 enhances the resolution of inflammation by specifically inducing
      neutrophil apoptosis.
AB  - Neutrophils play a central role in innate immunity and are rapidly recruited to
      sites of infection and injury. Neutrophil apoptosis is essential for the
      successful resolution of inflammation. Necrostatin-1 (Nec-1,methyl-thiohydantoin
      tryptophan (MTH-Trp)), is a potent and specific inhibitor of necroptosis[1] (a
      newly identified type of cell death representing a form of programmed necrosis or
      regulated non apoptotic cell death) by inhibiting the receptor interacting
      protein 1(RIP1) kinase. Here we report that Nec-1 specifically induces caspase
      dependent neutrophils apoptosis and overrides powerful anti-apoptosis signaling
      from survival factors such as GM-CSF and LPS. We showed that Nec-1 markedly
      enhanced the resolution of established neutrophil-dependent inflammation in LPS
      induced acute lung injury in mice. We also provided evidence that Nec-1 promoted
      apoptosis by reducing the expression of the anti-apoptotic protein Mcl-1 and
      increasing the expression of pro-apoptotic protein Bax. Thus, Nec-1 is not only
      an inhibitor of necroptosis, but also a promoter of apoptosis, of neutrophils,
      enhancing the resolution of established inflammation by inducing apoptosis of
      inflammatory cells. Our results suggest that Nec-1 may have potential roles for
      the treatment of diseases with increased or persistent inflammatory responses. 

PMID- 27027362
TI  - Managing Opioid Abuse in Older Adults: Clinical Considerations and Challenges.
AB  - Opioid use disorder is a public health epidemic. There is increasing attention
      being given to opioid abuse and overdose in the United States. The overall use of
      illicit substances by older adults is on the rise and in part can be attributed
      to the aging of Baby Boomers. Furthermore, much attention is being given to
      prescription opioid drug overdose, but it is important to note that heroin
      related deaths have also increased sharply. Heroin use is part of a larger
      substance abuse problem, with more than nine in 10 individuals who use heroin
      also using at least one other drug (e.g., cocaine, prescription opioid
      medication). The current article highlights treatment approaches, namely
      buprenorphine, buprenorphine/naloxone, and naltrexone; insurance considerations;
      and resources to aid in understanding and managing this public health crisis.

PMID- 27027364
TI  - Prophylactic Left Internal Mammary Artery Graft In Mildly-Stenosed Coronary
      Lesions. Still An Open Discussion.

PMID- 27027365
TI  - Reproducibility and Reliability of the Quality of Life Questionnaire in Patients
      With Atrial Fibrillation.
AB  - BACKGROUND: Studies have shown the impact of atrial fibrillation (AF) on the
      patients' quality of life. Specific questionnaires enable the evaluation of
      relevant events. We previously developed a questionnaire to assess the quality of
      life of patients with AF (AFQLQ version 1), which was reviewed in this study, and
      new domains were added. OBJECTIVE: To demonstrate the reproducibility of the
      AFQLQ version 2 (AFQLQ v.2), which included the domains of fatigue, illness
      perception and well-being. METHODS: We applied 160 questionnaires (AFQLQ v.2 and
      SF-36) to 40 patients, at baseline and 15 days after, to measure inter- and
      intraobserver reproducibility. The analysis of quality of life stability was
      determined by test-retest, applying the Bartko intraclass correlation coefficient
      (ICC). Internal consistency was assessed by Cronbach's alpha test. RESULTS: The
      total score of the test-retest (n = 40) had an ICC of 0.98 in the AFQLQ v.2, and
      of 0.94 in the SF36. In assessing the intra- and interobserver reproducibility of
      the AFQLQ v.2, the ICC reliability was 0.98 and 0.97, respectively. The internal
      consistency had a Cronbach's alpha coefficient of 0.82, compatible with good
      agreement of the AFQLQ v.2. CONCLUSION: The AFQLQ v.2 performed better than its
      previous version. Similarly, the domains added contributed to make it more
      comprehensive and robust to assess the quality of life of patients with AF.

PMID- 27027366
TI  - Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk
      Factors of Metabolic Syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS) is associated with a higher risk of all
      cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic
      marker of inflammation usually increased in MetS. Women with MetS-related
      diseases present higher hsCRP levels than men with MetS-related diseases,
      suggesting sex differences in inflammatory markers. However, it is unclear
      whether serum hsCRP levels are already increased in men and/or women with MetS
      risk factors and without overt diseases or under pharmacological treatment.
      OBJECTIVE: To determine the impact of the number of MetS risk factors on serum
      hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men
      and 48 women; 36 +/- 1 years) were divided into four groups according to the
      number of MetS risk factors: healthy group (CT; no risk factors), MetS <= 2, MetS
      = 3, and MetS >= 4. Blood was drawn after 12 hours of fasting for measurement of
      biochemical variables and hsCRP levels, which were determined by
      immunoturbidimetric assay. RESULTS: The groups with MetS risk factors presented
      higher serum hsCRP levels when compared with the CT group (p < 0.02). There were
      no differences in hsCRP levels among groups with MetS risk factors (p > 0.05).
      The best linear regression model to explain the association between MetS risk
      factors and hsCRP levels included waist circumference and HDL cholesterol (r =
      0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when
      compared with men (p sex < 0.01). CONCLUSIONS: Despite the absence of overt
      diseases and pharmacological treatment, subjects with MetS risk factors already
      presented increased hsCRP levels, which were significantly higher in women than
      men at similar conditions.

PMID- 27027367
TI  - When is the Best Time for the Second Antiplatelet Agent in Non-St Elevation Acute
      Coronary Syndrome?
AB  - Dual antiplatelet therapy is a well-established treatment in patients with non-ST
      elevation acute coronary syndrome (NSTE-ACS), with class I of recommendation
      (level of evidence A) in current national and international guidelines.
      Nonetheless, these guidelines are not precise or consensual regarding the best
      time to start the second antiplatelet agent. The evidences are conflicting, and
      after more than a decade using clopidogrel in this scenario, benefits from the
      routine pretreatment, i.e. without knowing the coronary anatomy, with dual
      antiplatelet therapy remain uncertain. The recommendation for the upfront
      treatment with clopidogrel in NSTE-ACS is based on the reduction of non-fatal
      events in studies that used the conservative strategy with eventual invasive
      stratification, after many days of the acute event. This approach is different
      from the current management of these patients, considering the established
      benefits from the early invasive strategy, especially in moderate to high-risk
      patients. The only randomized study to date that specifically tested the
      pretreatment in NSTE-ACS in the context of early invasive strategy, used
      prasugrel, and it did not show any benefit in reducing ischemic events with
      pretreatment. On the contrary, its administration increased the risk of bleeding
      events. This study has brought the pretreatment again into discussion, and led to
      changes in recent guidelines of the American and European cardiology societies.
      In this paper, the authors review the main evidence of the pretreatment with dual
      antiplatelet therapy in NSTE-ACS. 

PMID- 27027368
TI  - Ezetimibe: Clinical and Scientific Meaning of the IMPROVE-IT Study.

PMID- 27027369
TI  - Case 1/2016--56-Year-Old Male with Atrial Septal Defect, Pulmonary Arterial
      Hypertension, Hospitalized Due to Eisenmenger Syndrome.

PMID- 27027370
TI  - Giant and Calcified Post-Infarction True Left Ventricular Aneurysm: What to Do?

PMID- 27027371
TI  - Three-dimensional Echocardiography for Percutaneous Occlusion of Patent Foramen
      Ovale.

PMID- 27027373
TI  - Erratum.

PMID- 27027372
TI  - Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Heart Failure.

PMID- 27027374
TI  - Performance of optimized noncanonical amino acid mutagenesis systems in the
      absence of release factor 1.
AB  - Site-specific incorporation of noncanonical amino acids (ncAAs) into proteins
      expressed in E. coli using UAG-suppression competes with termination mediated by
      release factor 1 (RF1). Recently, unconditional deletion of RF1 was achieved in a
      genomically recoded E. coli (C321), devoid of all endogenous UAG stop codons.
      Here we evaluate the efficiency of ncAA incorporation in this strain using
      optimized suppression vectors. Even though the absence of RF1 does not benefit
      the suppression efficiency of a single UAG codon, multi-site incorporation of a
      series of chemically distinct ncAAs was significantly improved.

PMID- 27027375
TI  - Real-time quantitative nicking endonuclease-mediated isothermal amplification
      with small molecular beacons.
AB  - Techniques of isothermal amplification have recently made great strides, and have
      generated significant interest in the field of point-of-care detection. Nicking
      endonuclease-mediated isothermal amplification (NEMA) is an example of simple
      isothermal technology. In this paper, a real-time quantitative nicking
      endonuclease-mediated isothermal amplification with small molecular beacons (SMB
      NEMA) of improved specificity and sensitivity is described. First, we optimized
      the prohibition of de novo synthesis by choosing Nt.BstNBI endonuclease. Second,
      the whole genome was successfully amplified with Nt.BstNBI (6 U), betaine (1 M)
      and trehalose (60 mM) for the first time. Third, we achieved 10 pg sensitivity
      for the first time after adding a small molecular beacon that spontaneously
      undergoes a conformational change when hybridizing to target, and the practical
      test validated the assay's application. The small molecular beacon has a similar
      melting temperature to the reaction temperature, but is approximately 10 bp
      shorter than the length of a traditional molecular beacon. A new threshold
      regulation was also established for isothermal conditions. Finally, we
      established a thermodynamic model for designing small molecular beacons. This
      multistate model is more correct than the traditional algorithm. This theoretical
      and practical basis will help us to monitor SMB-NEMA in a quantitative way. In
      summary, our SMB-NEMA method allows the simple, specific and sensitive assessment
      of isothermal DNA quantification. 

PMID- 27027376
TI  - Shifting away from sedentary time, and FITTing exercise into the treatment of
      hypertension.

PMID- 27027377
TI  - Combining sodium-dependent glucose co-transporter 2 inhibition with conventional
      diuretics: Dr Jekyll and Mr Hyde?

PMID- 27027378
TI  - High blood pressure in US diabetic veterans with normal renal function: a plea
      for the design of a more powerful and conclusive outcome trial.

PMID- 27027379
TI  - Optimizing inhibition of the renin-angiotensin system in hypertension.

PMID- 27027380
TI  - Does electrocardiography still have a place in hypertension?

PMID- 27027381
TI  - Predictors of blood pressure response to spironolactone.

PMID- 27027382
TI  - Nonlinear relation between pulse pressure and coronary heart disease in patients
      with type 2 diabetes or hypertension.
AB  - OBJECTIVES: Wide pulse pressure (PP) is an independent predictor of coronary
      heart disease (CHD). However, the linearity of the relation between PP and CHD
      was not examined before. We aimed to examine this relation in patients with type
      2 diabetes and/or hypertension. METHODS: A total of 3120 patients (including 2607
      with diabetes and 1586 with hypertension) were followed for 7.8 years. Physician
      adjudicated first hard CHD event was the primary outcome. Cox regression analysis
      was used to investigate the association between PP and incident CHD. Restricted
      cubic splines were used to investigate nonlinear relations. RESULTS: Four spline
      covariates were defined between 30, 40, 50, 60, and 70 mmHg. The null-hypothesis
      of the linearity of the relation between PP and CHD was rejected (P value =
      0.004). The second, third, and fourth spline covariates were significant (P value
      = 0.02, P value = 0.02 and P value = 0.01, respectively), supporting a nonlinear
      relation in corresponding PP intervals. Patients with PP less than 45 mmHg and PP
      more than 55 mmHg had increased risk of future CHD event, compared with those
      with PP between 45 and 55 mmHg [hazard ratio (HR) = 1.33 (1.00-1.77) and HR =
      1.67 (1.23-2.27), respectively]. This remained significant after controlling for
      systolic, diastolic, or mean arterial pressures in wide PP group. However,
      adjustment for traditional cardiovascular risk factors (especially age)
      attenuated the relation in those with wide PP. CONCLUSION: The relation between
      PP and CHD is nonlinear in patients with type 2 diabetes and hypertension. Both
      narrow and wide PPs increase risk of future hard CHD events. The association
      between wide PP and CHD is independent from SBP, DBP, or mean arterial pressure.

PMID- 27027383
TI  - Pattern discovery in critical alarms originating from neonates under intensive
      care.
AB  - Patient monitoring generates a large number of alarms, the vast majority of which
      are false. Excessive non-actionable medical alarms lead to alarm fatigue, a well
      recognized patient safety issue. While multiple approaches to reduce alarm
      fatigue have been explored, patterns in alarming and inter-alarm relationships,
      as they manifest in the clinical workspace, are largely a black-box and hamper
      research efforts towards reducing alarms. The aim of this study is to detect
      opportunities to safely reduce alarm pressure, by developing techniques to
      identify, capture and visualize patterns in alarms. Nearly 500 000 critical
      medical alarms were acquired from a neonatal intensive care unit over a 20 month
      period. Heuristic techniques were developed to extract the inter-alarm
      relationships. These included identifying the presence of alarm clusters,
      patterns of transition from one alarm category to another, temporal associations
      amongst alarms and determination of prevalent sequences in which alarms manifest.
      Desaturation, bradycardia and apnea constituted 86% of all alarms and
      demonstrated distinctive periodic increases in the number of alarms that were
      synchronized with nursing care and enteral feeding. By inhibiting further alarms
      of a category for a short duration of time (30 s/60 s), non-actionable
      physiological alarms could be reduced by 20%. The patterns of transition from one
      alarm category to another and the time duration between such transitions revealed
      the presence of close temporal associations and multiparametric derangement.
      Examination of the prevalent alarm sequences reveals that while many sequences
      comprised of multiple alarms, nearly 65% of the sequences were isolated instances
      of alarms and are potentially irreducible. Patterns in alarming, as they manifest
      in the clinical workspace were identified and visualized. This information can be
      exploited to investigate strategies for reducing alarms. 

PMID- 27027384
TI  - Anticoagulants (extended duration) for prevention of venous thromboembolism
      following total hip or knee replacement or hip fracture repair.
AB  - BACKGROUND: The optimal duration of thromboprophylaxis after total hip or knee
      replacement, or hip fracture repair remains controversial. It is common practice
      to administer prophylaxis using low-molecular-weight heparin (LMWH) or
      unfractionated heparin (UFH) until discharge from hospital, usually seven to 14
      days after surgery. International guidelines recommend extending
      thromboprophylaxis for up to 35 days following major orthopaedic surgery but the
      recommendation is weak due to moderate quality evidence. In addition, recent oral
      anticoagulants that exert effect by direct inhibition of thrombin or activated
      factor X lack the need for monitoring and have few known drug interactions.
      Interest in this topic remains high. OBJECTIVES: To assess the effects of
      extended-duration anticoagulant thromboprophylaxis for the prevention of venous
      thromboembolism (VTE) in people undergoing elective hip or knee replacement
      surgery, or hip fracture repair. SEARCH METHODS: The Cochrane Vascular
      Information Specialist searched the Specialised Register (last searched May 2015)
      and CENTRAL (2015, Issue 4). Clinical trials databases were searched for ongoing
      or unpublished studies. SELECTION CRITERIA: Randomised controlled trials
      assessing extended-duration thromboprophylaxis (five to seven weeks) using
      accepted prophylactic doses of LMWH, UFH, vitamin K antagonists (VKA) or direct
      oral anticoagulants (DOAC) compared with short-duration thromboprophylaxis (seven
      to 14 days) followed by placebo, no treatment or similar extended-duration
      thromboprophylaxis with LMWH, UFH, VKA or DOACs in participants undergoing hip or
      knee replacement or hip fracture repair. DATA COLLECTION AND ANALYSIS: We
      independently selected trials and extracted data. Disagreements were resolved by
      discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs)
      and 95% confidence intervals (CIs). We used a random-effects model when there was
      heterogeneity. MAIN RESULTS: We included 16 studies (24,930 participants); six
      compared heparin with placebo, one compared VKA with placebo, two compared DOAC
      with placebo, one compared VKA with heparin, five compared DOAC with heparin and
      one compared anticoagulants chosen at investigators' discretion with placebo.
      Three trials included participants undergoing knee replacement. No studies
      assessed hip fracture repair.Trials were generally of good methodological
      quality. The main reason for unclear risk of bias was insufficient reporting. The
      quality of evidence according to GRADE was generally moderate, as some
      comparisons included a single study, low number of events or heterogeneity
      between studies leading to wide CIs.We showed no difference between extended
      duration heparin and placebo in symptomatic VTE (OR 0.59, 95% CI 0.35 to 1.01;
      2329 participants; 5 studies; high quality evidence), symptomatic deep vein
      thrombosis (DVT) (OR 0.73, 95% CI 0.39 to 1.38; 2019 participants; 4 studies;
      moderate quality evidence), symptomatic pulmonary embolism (PE) (OR 0.61, 95% CI
      0.16 to 2.33; 1595 participants; 3 studies; low quality evidence) and major
      bleeding (OR 0.59, 95% CI 0.14 to 2.46; 2500 participants; 5 studies; moderate
      quality evidence). Minor bleeding was increased in the heparin group (OR 2.01,
      95% CI 1.43 to 2.81; 2500 participants; 5 studies; high quality evidence).
      Clinically relevant non-major bleeding was not reported.We showed no difference
      between extended-duration VKA and placebo (one study, 360 participants) for
      symptomatic VTE (OR 0.10, 95% CI 0.01 to 1.94; moderate quality evidence),
      symptomatic DVT (OR 0.13, 95% CI 0.01 to 2.62; moderate quality evidence),
      symptomatic PE (OR 0.32, 95% CI 0.01 to 7.84; moderate quality evidence) and
      major bleeding (OR 2.89, 95% CI 0.12 to 71.31; low quality evidence). Clinically
      relevant non-major bleeding and minor bleeding were not reported.Extended
      duration DOAC showed reduced symptomatic VTE (OR 0.20, 95% CI 0.06 to 0.68; 2419
      participants; 1 study; moderate quality evidence) and symptomatic DVT (OR 0.18,
      95% CI 0.04 to 0.81; 2459 participants; 2 studies; high quality evidence)
      compared to placebo. No differences were found for symptomatic PE (OR 0.25, 95%
      CI 0.03 to 2.25; 1733 participants; 1 study; low quality evidence), major
      bleeding (OR 1.00, 95% CI 0.06 to 16.02; 2457 participants; 1 study; low quality
      evidence), clinically relevant non-major bleeding (OR 1.22, 95% CI 0.76 to 1.95;
      2457 participants; 1 study; moderate quality evidence) and minor bleeding (OR
      1.18, 95% CI 0.74 to 1.88; 2457 participants; 1 study; moderate quality
      evidence).We showed no difference between extended-duration anticoagulants chosen
      at investigators' discretion and placebo (one study, 557 participants, low
      quality evidence) for symptomatic VTE (OR 0.50, 95% CI 0.09 to 2.74), symptomatic
      DVT (OR 0.33, 95% CI 0.03 to 3.21), symptomatic PE (OR 1.00, 95% CI 0.06 to
      16.13), and major bleeding (OR 5.05, 95% CI 0.24 to 105.76). Clinically relevant
      non-major bleeding and minor bleeding were not reported.We showed no difference
      between extended-duration VKA and heparin (one study, low quality evidence) for
      symptomatic VTE (OR 1.64, 95% CI 0.85 to 3.16; 1279 participants), symptomatic
      DVT (OR 1.36, 95% CI 0.69 to 2.68; 1279 participants), symptomatic PE (OR 9.16,
      95% CI 0.49 to 170.42; 1279 participants), major bleeding (OR 3.87, 95% CI 1.91
      to 7.85; 1272 participants) and minor bleeding (OR 1.33, 95% CI 0.64 to 2.76;
      1279 participants). Clinically relevant non-major bleeding was not reported.We
      showed no difference between extended-duration DOAC and heparin for symptomatic
      VTE (OR 0.70, 95% CI 0.28 to 1.70; 15,977 participants; 5 studies; low quality
      evidence), symptomatic DVT (OR 0.60, 95% CI 0.11 to 3.27; 15,977 participants; 5
      studies; low quality evidence), symptomatic PE (OR 0.91, 95% CI 0.43 to 1.94;
      14,731 participants; 5 studies; moderate quality evidence), major bleeding (OR
      1.11, 95% CI 0.79 to 1.54; 16,199 participants; 5 studies; high quality
      evidence), clinically relevant non-major bleeding (OR 1.08, 95% CI 0.90 to 1.28;
      15,241 participants; 4 studies; high quality evidence) and minor bleeding (OR
      0.95, 95% CI 0.82 to 1.10; 11,766 participants; 4 studies; high quality
      evidence). AUTHORS' CONCLUSIONS: Moderate quality evidence suggests extended
      duration anticoagulants to prevent VTE should be considered for people undergoing
      hip replacement surgery, although the benefit should be weighed against the
      increased risk of minor bleeding. Further studies are needed to better understand
      the association between VTE and extended-duration oral anticoagulants in relation
      to knee replacement and hip fracture repair, as well as outcomes such as distal
      and proximal DVT, reoperation, wound infection and healing.

PMID- 27027385
TI  - Safety of prothrombin complex concentrate in healthy subjects.

PMID- 27027386
TI  - Neutralizing antibodies in patients with chronic hepatitis C and correlation to
      liver cirrhosis and estimated duration of infection.
AB  - Although chronic hepatitis C virus (HCV) infection accounts for 30% of
      individuals with cirrhotic livers worldwide, factors influencing disease
      progression are far from elucidated. The aim of this study was to determine
      whether the level of neutralizing antibodies (NAbs) correlated with the
      development of cirrhosis in patients with chronic HCV infection, genotype 1, when
      adjusting for estimated duration of infection. Thirty-nine patients with chronic
      hepatitis C, with either no/mild fibrosis (n = 23) or cirrhosis (n = 16), were
      enrolled from two university hospitals in Denmark. Duration of HCV infection was
      estimated based on patient information and/or anti-HCV seroconversion. Serial
      dilutions of purified serum/plasma derived IgGs were tested for their ability to
      neutralize six HCV-genotype 1 cell-culture strains. The results were expressed as
      the lowest IgG concentration yielding >=50% neutralization (NAb50 -titer). A
      significant difference in HCV NAb50 -titers among the six genotype 1a/1b
      recombinants was found. In patients with cirrhosis, a tendency for higher level
      of NAbs was observed compared to patients with no/mild fibrosis, although not
      statistical significant. Stratifying the two groups revealed that being infected
      >25 years resulted in higher levels of NAbs in both. Furthermore, by correlating
      estimated duration of HCV infection to NAb50 -titers a significant result was
      found against two recombinants. The NAb titer does not differ significantly
      between HCV patients with either no/mild fibrosis or cirrhosis but show a
      tendency for increasing level with increased duration of infection. NAbs might
      contribute as a biological marker to increase the accuracy of patient based
      information on duration of HCV infection. J. Med. Virol. 88:1791-1803, 2016. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27027387
TI  - Biological performance of functionalized biomedical polymers for potential
      applications as intraocular lens.
AB  - To study the biological performance of surface-modified biomedical polymer
      materials, a model of the functional mechanism of nonspecific adsorption
      resistance was constructed. Cell behavior on the surface and in vivo
      transplantation features of intraocular lens (IOL) materials, such as hydrophobic
      acrylic ester and polymethyl methacrylate (PMMA), were investigated. The results
      of cell adhesion and proliferation studies showed that the addition of hirudin
      can significantly resist epithelial cell adhesion, better than the pure amination
      process, and thereby inhibit excessive proliferation on the surface. Experiments
      on the eyes of rabbits indicated that the IOL surfaces with hirudin modification
      reduced the incidence of cell aggregation and inflammation. Combined with a study
      of protein-resistant layer construction with recombinant hirudin on the material
      surface, the mechanism of surface functionalization was determined. The
      biological performance indicated that nonspecific adsorption is greatly decreased
      due to the existence of amphiphilic ions or hydration layers, which lead to
      stability and long-term resistance to nonspecific adsorption. These results offer
      a theoretical basis for the use of traditional biomedical polymer materials in
      long-term clinical applications. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 104A: 1961-1967, 2016.

PMID- 27027388
TI  - Drug survival of biologic therapy in a large, disease-based registry of patients
      with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry
      (PSOLAR).
AB  - BACKGROUND: Drug survival is a marker for treatment sustainability in chronic
      diseases such as psoriasis. OBJECTIVE: The aim of these analyses was to assess
      survival of biologic treatments in the PSOriasis Longitudinal Assessment and
      Registry (PSOLAR). METHODS: PSOLAR is a large, prospective, international,
      disease-based registry of patients with psoriasis receiving (or eligible for)
      systemic therapy in a real-world setting. Drug survival is defined as the time
      from initiation to discontinuation (stop/switch) of biologic therapy on registry.
      The number of patients who discontinued each treatment and the duration of
      therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression
      analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to
      discontinuation was compared across cohorts undergoing first-, second- or third
      line treatment with ustekinumab, infliximab, adalimumab or etanercept. RESULTS:
      As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR.
      Of the 4000 patients initiating any new biologic therapy, approximately 3500
      started a first-line, second-line or third-line biologic therapy during the
      registry. Lack of effectiveness was the most common reason for discontinuation
      across biologic therapies. Based on the multivariate analysis, significantly
      shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73
      (1.48-5.04), P = 0.0014]; adalimumab [4.16 (2.80-6.20), P < 0.0001]; and
      etanercept [4.91 (3.28-7.35) P < 0.0001] compared with ustekinumab [reference
      treatment]) for first-line biologic use; results were similar for treatment
      effects for second/third-line therapies. Although limited in power, analyses in
      patients with concurrent psoriatic arthritis confirmed by a rheumatologist
      reflect observations in the overall psoriasis population. CONCLUSION: Drug
      survival was superior for ustekinumab compared with infliximab, adalimumab and
      etanercept in patients with psoriasis.

PMID- 27027389
TI  - Structure-Resistance Relationships: Interrogating Antiseptic Resistance in
      Bacteria with Multicationic Quaternary Ammonium Dyes.
AB  - Bacterial resistance toward commonly used biocides is a widespread yet
      underappreciated problem, one which needs not only a deeper understanding of the
      mechanisms by which resistance proliferates, but also means for mitigation. To
      advance our understanding of this issue, we recognized a polyaromatic structural
      core analogous to activators of QacR, a negative transcriptional regulator of the
      efflux pump QacA, and envisioned a series of quaternary ammonium compounds (QACs)
      based on this motif. Using commercially available dye scaffolds, we synthesized
      and evaluated the antimicrobial activity of 52 novel QACs bearing 1-3 quaternary
      ammonium centers. Striking differences in antimicrobial activity against bacteria
      bearing QAC resistance genes have been observed, with up to a 125-fold increase
      in minimum inhibitory concentration (MIC) for select structures against bacteria
      known to bear efflux pumps. Based on these findings, general trends in structure
      resistance relationships have been identified, laying the groundwork for future
      mechanistic studies.

PMID- 27027390
TI  - High-Performance Flexible Transparent Electrode with an Embedded Metal Mesh
      Fabricated by Cost-Effective Solution Process.
AB  - A new structure of flexible transparent electrodes is reported, featuring a metal
      mesh fully embedded and mechanically anchored in a flexible substrate, and a cost
      effective solution-based fabrication strategy for this new transparent electrode.
      The embedded nature of the metal-mesh electrodes provides a series of advantages,
      including surface smoothness that is crucial for device fabrication, mechanical
      stability under high bending stress, strong adhesion to the substrate with
      excellent flexibility, and favorable resistance against moisture, oxygen, and
      chemicals. The novel fabrication process replaces vacuum-based metal deposition
      with an electrodeposition process and is potentially suitable for high
      throughput, large-volume, and low-cost production. In particular, this strategy
      enables fabrication of a high-aspect-ratio (thickness to linewidth) metal mesh,
      substantially improving conductivity without considerably sacrificing
      transparency. Various prototype flexible transparent electrodes are demonstrated
      with transmittance higher than 90% and sheet resistance below 1 ohm sq(-1) , as
      well as extremely high figures of merit up to 1.5 * 10(4) , which are among the
      highest reported values in recent studies. Finally using our embedded metal-mesh
      electrode, a flexible transparent thin-film heater is demonstrated with a low
      power density requirement, rapid response time, and a low operating voltage. 

PMID- 27027391
TI  - Blood vessel occlusion in peri-burn tissue is secondary to erythrocyte
      aggregation and mitigated by a fibronectin-derived peptide that limits burn
      injury progression.
AB  - Although vascular occlusion has long been noted in peri-burn tissue, the
      literature is inconsistent regarding the nature of the occlusion, with articles
      in the 1940s claiming that erythrocytes were the culprit and in the 1980s-1990s
      that microthrombi were responsible. To better define the nature of vessel
      occlusion, we studied two porcine burn models, a hot comb horizontal injury model
      and a vertical injury progression model. In both cases, tissue from the first two
      days after burn were stained with hemotoxylin and eosin, or probed for platelets
      or for fibrinogen/fibrin. Erythrocytes, identified as nonstained, clumped,
      anuclear, 5 um cells, occluded most blood vessels (BVs) in both burn models. In
      contrast, platelet or fibrinogen/fibrin antibodies stained BV occlusions
      minimally at early time points, and only up to 16% of deep dermal BVs at 48 hours
      in the hot comb model and up to 7% at 24 hours in the vertical injury progression
      model. Treatment of animals with a fibronectin-derived peptide (P12), which
      limits burn injury progression and can dilate peripheral microvasculature,
      reduced erythrocyte occlusion by at least 50%, speeded healing and reduced
      scarring. Early erythrocyte aggregation, rather than thrombosis, explains the
      ineffectiveness of anticoagulants to prevent burn injury progression.

PMID- 27027392
TI  - Establishment of review criteria for a hematology analyzer with an automated
      review function.

PMID- 27027393
TI  - Endovascular treatment of aortoiliac aneurysms: From intentional occlusion of the
      internal iliac artery to branch iliac stent graft.
AB  - Approximately 20%-40% of patients with abdominal aortic aneurysms can have
      unilateral or bilateral iliac artery aneurysms and/or ectasia. This influences
      and compromises the distal sealing zone during endovascular aneurysm repair.
      There are a few endovascular techniques that are used to treat these types of
      aneurysms, including intentional occlusion/over-stenting of the internal iliac
      artery on one or both sides, the "bell-bottom" technique, and the more recent
      method of using an iliac branch stent graft. In some cases, other options include
      the "snorkel and sandwich" technique and hybrid interventions. Pelvic ischemia,
      represented as buttock claudication, has been reported in 16%-55% of cases; this
      is followed by impotence, which has been described in 10%-17% of cases following
      internal iliac artery occlusion. The bell-bottom technique can be used for a
      common iliac artery up to 24 mm in diameter given that the largest diameter of
      the stent graft is 28 mm. There is a paucity of data and evidence regarding the
      "snorkel and sandwich" technique, which can be used in a few clinical scenarios.
      The hybrid intervention is comprised of a surgical operation, and is not purely
      endovascular. The newest branch stent graft technology enables preservation of
      the anterograde flow of important side branches. Technical success with the
      newest technique ranges from 85%-96.3%, and in some small series, technical
      success is 100%. Buttock claudication was reported in up to 4% of patients
      treated with a branch stent graft at 5-year follow-up. Mid- and short-term follow
      up results showed branch patency of up to 88% during the 5-6-year period.
      Furthermore, branch graft occlusion is a potential complication, and it has been
      described to occur in 1.2%-11% of cases. Iliac branch stent graft placement
      represents a further development in endovascular medicine, and it has a high
      technical success rate without serious complications. 

PMID- 27027395
TI  - US dermatologists' knowledge of current sunscreen recommendations.

PMID- 27027394
TI  - Role of patient factors, preferences, and distrust in health care and access to
      liver transplantation and organ donation.
AB  - Despite major improvements in access to liver transplantation (LT), disparities
      remain. Little is known about how distrust in medical care, patient preferences,
      and the origins shaping those preferences contribute to differences surrounding
      access. We performed a single-center, cross-sectional survey of adults with end
      stage liver disease and compared responses between LT listed and nonlisted
      patients as well as by race. Questionnaires were administered to 109 patients (72
      nonlisted; 37 listed) to assess demographics, health care system distrust (HCSD),
      religiosity, and factors influencing LT and organ donation (OD). We found that
      neither HCSD nor religiosity explained differences in access to LT in our
      population. Listed patients attained higher education levels and were more likely
      to be insured privately. This was also the case for white versus black patients.
      All patients reported wanting LT if recommended. However, nonlisted patients were
      significantly less likely to have discussed LT with their physician or to be
      referred to a transplant center. They were also much less likely to understand
      the process of LT. Fewer blacks were referred (44.4% versus 69.7%; P = 0.03) or
      went to the transplant center if referred (44.4% versus 71.1%; P = 0.02). Fewer
      black patients felt that minorities had as equal access to LT as whites (29.6%
      versus 57.3%; P < 0.001). For OD, there were more significant differences in
      preferences by race than listing status. More whites indicated OD status on their
      driver's license, and more blacks were likely to become an organ donor if
      approached by someone of the same cultural or ethnic background (P < 0.01). In
      conclusion, our analysis demonstrates persistent barriers to LT and OD. With
      improved patient and provider education and communication, many of these
      disparities could be successfully overcome. Liver Transplantation 22 895-905 2016
      AASLD.

PMID- 27027396
TI  - Periodontal conditions among employed adults in Spain.
AB  - AIM: To assess the prevalence and severity of periodontal conditions among a
      representative sample of employed adults in Spain. MATERIAL AND METHODS: A
      national cross-sectional study was conducted during 2008-2011. Periodontal status
      of 5130 workers, stratified by gender, age and occupation, was assessed based on
      Community Periodontal Index (CPI) and Clinical Attachment Level (CAL), following
      the WHO criteria. RESULTS: The percentage of subjects with periodontal pockets
      (CPI codes 3-4) was 38.4%, [95% Confidence Interval (CI): 36.4-40.5] increasing
      significantly in subjects >=45 years; 13.7% (95% CI: 12.8-14.7) of workers showed
      CAL 4-5 mm, while 7.7% (95% CI: 7.0-8.5) showed CAL >=6 mm, again increasing
      significantly in the population >=45 years. Prevalence of worse periodontal
      conditions was significantly higher in male workers, in subjects with primary
      school education and lower income, and in smokers and former smokers. The
      periodontal condition in young adults (35-44 years) was worse in comparison with
      those previously reported in Spanish national surveys. CONCLUSION: Prevalence of
      destructive periodontal diseases was age-, gender-, education-, income- and
      tobacco smoking-related. Young adults showed worse periodontal conditions than
      has been previously reported in national surveys in Spain. It is suggested to
      include oral evaluation and preventive strategies in work-related medical check
      ups.

PMID- 27027398
TI  - Titanium: a review on exposure, release, penetration, allergy, epidemiology, and
      clinical reactivity.
AB  - Exposure to titanium (Ti) from implants and from personal care products as
      nanoparticles (NPs) is common. This article reviews exposure sources, ion
      release, skin penetration, allergenic effects, and diagnostic possibilities. We
      conclude that human exposure to Ti mainly derives from dental and medical
      implants, personal care products, and foods. Despite being considered to be
      highly biocompatible relative to other metals, Ti is released in the presence of
      biological fluids and tissue, especially under certain circumstances, which seem
      to be more likely with regard to dental implants. Although most of the studies
      reviewed have important limitations, Ti seems not to penetrate a competent skin
      barrier, either as pure Ti, alloy, or as Ti oxide NPs. However, there are some
      indications of Ti penetration through the oral mucosa. We conclude that patch
      testing with the available Ti preparations for detection of type IV
      hypersensitivity is currently inadequate for Ti. Although several other methods
      for contact allergy detection have been suggested, including lymphocyte
      stimulation tests, none has yet been generally accepted, and the diagnosis of Ti
      allergy is therefore still based primarily on clinical evaluation. Reports on
      clinical allergy and adverse events have rarely been published. Whether this is
      because of unawareness of possible adverse reactions to this specific metal,
      difficulties in detection methods, or the metal actually being relatively safe to
      use, is still unresolved. 

PMID- 27027397
TI  - How to diagnose mould allergy? Comparison of skin prick tests with specific IgE
      results.
AB  - BACKGROUND: Diagnosis of mould allergy is complicated due to the heterogeneity of
      the test material and the decrease in the number of commercial mould skin test
      solutions that are currently available. OBJECTIVES: The aim of this study was to
      compare skin prick tests (SPT) from different manufacturers to one another and
      concurrently with sIgE tests for Aspergillus fumigatus (Asp f), Cladosporium
      herbarum (Cla h), Penicillium chrysogenum (Pen ch), Alternaria alternata (Alt a)
      and Aspergillus versicolor (Asp v) to ascertain a feasible diagnostic procedure
      for mould sensitization. METHODS: In this multi-centre study, 168 patients with
      mould exposure and/or mould-induced respiratory symptoms were included. Mould SPT
      solutions were analysed biochemically and tested in duplicate on patients' arms.
      Specific IgE (sIgE) concentrations to corresponding mould species and mould mix
      (mx1) were measured by ImmunoCAP. SPTs in accordance with one another and with
      sIgE were further considered. The test efficiency was calculated using receiver
      operating characteristic (ROC) analysis. RESULTS: Mould sensitization was more
      frequently detected by the SPT (90 of 168) than by the sIgE tests (56 of 168).
      Concordances of double SPT positives were only sufficient (>= 80%) for
      environmental allergens, two Asp f and three Alt a SPT solutions, whereas all
      other mould solutions revealed concordances < 80%. The antigen content of SPT
      solutions was positively associated with concordant SPT double values as well as
      with sIgE. Taking sIgE as the 'positive standard', all mould SPT solutions
      revealed test efficiencies > 80%, but varied up to 20% in sensitivity and
      positive predictive value with the exception of Alt a. CONCLUSIONS: SPT solutions
      are sensitive and essential diagnostic tools for the detection of mould
      sensitization. Our recommendation for diagnosis would be to test at least Alt a,
      Asp f and Pen ch using SPT and additional sIgE test to mx1.

PMID- 27027399
TI  - Acute development of keratoacanthoma at a full-thickness skin graft donor site
      shortly after surgery.

PMID- 27027400
TI  - Insect transformation with piggyBac: getting the number of injections just right.
AB  - The insertion of exogenous genetic cargo into insects using transposable elements
      is a powerful research tool with potential applications in meeting food security
      and public health challenges facing humanity. piggyBac is the transposable
      element most commonly utilized for insect germline transformation. The described
      efficiency of this process is variable in the published literature, and a
      comprehensive review of transformation efficiency in insects is lacking. This
      study compared and contrasted all available published data with a comprehensive
      data set provided by a biotechnology group specializing in insect transformation.
      Based on analysis of these data, with particular focus on the more complete
      observational data from the biotechnology group, we designed a decision tool to
      aid researchers' decision-making when using piggyBac to transform insects by
      microinjection. A combination of statistical techniques was used to define
      appropriate summary statistics of piggyBac transformation efficiency by species
      and insect order. Publication bias was assessed by comparing the data sets. The
      bias was assessed using strategies co-opted from the medical literature. The work
      culminated in building the Goldilocks decision tool, a Markov-Chain Monte-Carlo
      simulation operated via a graphical interface and providing guidance on best
      practice for those seeking to transform insects using piggyBac.

PMID- 27027401
TI  - Physiological adaptations to chronic stress in healthy humans - why might the
      sexes have evolved different energy utilisation strategies?
AB  - KEY POINTS: The human stress response activates the autonomic nervous system and
      endocrine systems to increase performance during environmental challenges. This
      response is usually beneficial, improving the chance of overcoming environmental
      challenges, but costs resources such as energy. Humans and other animals are
      known to adapt their responses to acute stress when they are stimulated
      chronically, presumably to optimise resource utilisation. Characterisation of
      these adaptations has been limited. Using advanced imaging techniques, we show
      that cardiovascular and endocrine physiology, reflective of energy utilisation
      during acute stress, and energy storage (fat) differ between the sexes when they
      are exposed to chronic stress. We examine possible evolutionary explanations for
      these differences, related to energy use, and point out how these physiological
      differences could underpin known disparities between the sexes in their risk of
      important cardiometabolic disorders such as obesity and cardiovascular disease.
      ABSTRACT: Obesity and associated diseases, such as cardiovascular disease, are
      the dominant human health problems in the modern era. Humans develop these
      conditions partly because they consume excess energy and exercise too little.
      Stress might be one of the factors contributing to these disease-promoting
      behaviours. We postulate that sex-specific primordial energy optimisation
      strategies exist, which developed to help cope with chronic stress but have
      become maladaptive in modern societies, worsening health. To demonstrate the
      existence of these energy optimisation strategies, we recruited 88 healthy adults
      with varying adiposity and chronic stress exposure. Cardiovascular physiology at
      rest and during acute stress (Montreal Imaging Stress Task), and body fat
      distribution were measured using advanced magnetic resonance imaging methods,
      together with endocrine function, cardiovascular energy use and cognitive
      performance. Potential confounders such as lifestyle, social class and employment
      were accounted for. We found that women exposed to chronic stress had lower
      adiposity, greater acute stress cardiovascular responses and better cognitive
      performance. Conversely, chronic stress-exposed men had greater adiposity and
      lower cardiovascular responses to acute stress. These results provide initial
      support for our hypothesis that differing sex-specific energy conservation
      strategies exist. We propose that these strategies have initially evolved to
      benefit humans but are now maladaptive and increase the risk of disorders such as
      obesity, especially in men exposed to chronic stress.

PMID- 27027402
TI  - Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2
      dependent mechanism.
AB  - Hepatic stellate cells (HSCs) are universally acknowledged to play a stimulative
      role in the pathogenesis of hepatic fibrosis and portal hypertension. HSCs when
      activated in response to liver injury are characterized with many changes, with
      HSC contraction being the most common cause of portal hypertension. Previous
      studies have shown that dihydroartemisinine (DHA) is a potential antifibrotic
      natural product by inducing HSC apoptosis, whereas the role of DHA in regulating
      HSC contraction and the mechanisms involved remain a riddle. Recent studies have
      emphasized on the importance of farnesoid X receptor (FXR) and sphingosine-1
      phosphate receptor 2 (S1PR2) in controlling cell contractility. This study showed
      that DHA strongly induced the mRNA and protein expression of FXR in LX-2 cells in
      a dose- and time-dependent manner and inhibited HSC activation, implying a
      conceivable impact of DHA on HSC contraction. The gel contraction assays and
      fluorescence staining of actin cytoskeleton verified that DHA dose-dependently
      limited contraction of collagen lattices and reorganization of actin stress
      fibers in LX-2 cells. DHA also decreased the phosphorylation of myosin light
      chain that is responsible for the contractile force of HSCs. Furthermore, gain-
      or loss-of-function analyses exhibited a FXR- and S1PR2-dependent mechanism of
      inhibiting HSC contraction by DHA, and DHA decreased S1PR2 expression by
      modulating FXR activation. Subsequent work revealed that inhibition of both
      Ca(2+) -dependent and Ca(2+) -sensitization signaling transductions contributed
      to DHA-induced HSC relaxation. In summary, these findings suggest that DHA could
      restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) 
      dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a
      potential candidate for portal hypertension. (c) 2016 IUBMB Life 68(5):376-387,
      2016.

PMID- 27027403
TI  - Effects of an invasive ant on land snails in the Ogasawara Islands.
AB  - We investigated how Pheidole megacephala has affected endemic achatinellid snails
      because these snails are excellent indicators of the impact of ants and they have
      high conservation value in Ogasawara. In 2015 we surveyed the Minamizaki area of
      Hahajima Island of Ogasawara, designated a core zone of the World Heritage Site,
      for P. megacephala. In Minamizaki, we determined the distribution and density of
      achatinellid snails in 2015 and compared these data with their distribution and
      density in 2005. Land cover in the survey area was entirely forest. We also
      tested whether P. megacephala preyed on achatinellid snails in the laboratory. P.
      megacephala was present in the forested areas of Minamizaki. Achatinellid snails
      were absent in 19 of 39 sites where P. megacephala was present, whereas in other
      areas densities of the snails ranged from 2 to 228 individuals/site. In the
      laboratory, P. megacephala carried 6 of 7 achatinellid snails and a broken shell
      was found. Snail distribution and density comparisons and results of the feeding
      experiments suggest that the presence of P. megacephala has contributed to the
      decline of achatinellid snails in forests in the survey area. Yet, P. megacephala
      is not on the official list of invasive non-native species. Stakeholders using
      the list of invasive species to develop conservation programs should recognize
      that invasiveness of non-native species differs depending on the ecosystem and
      that official lists may not be complete.

PMID- 27027404
TI  - Polyphosphazene Based Star-Branched and Dendritic Molecular Brushes.
AB  - A new synthetic procedure is described for the preparation of
      poly(organo)phosphazenes with star-branched and star dendritic molecular brush
      type structures, thus describing the first time it has been possible to prepare
      controlled, highly branched architectures for this type of polymer. Furthermore,
      as a result of the extremely high-arm density generated by the phosphazene repeat
      unit, the second-generation structures represent quite unique architectures for
      any type of polymer. Using two relativity straight forward iterative syntheses it
      is possible to prepare globular highly branched polymers with up to 30 000
      functional end groups, while keeping relatively narrow polydispersities (1.2
      1.6). Phosphine mediated polymerization of chlorophosphoranimine is first used to
      prepare three-arm star polymers. Subsequent substitution with diphenylphosphine
      moieties gives poly(organo)phosphazenes to function as multifunctional
      macroinitiators for the growth of a second generation of polyphosphazene arms.
      Macrosubstitution with Jeffamine oligomers gives a series of large, water soluble
      branched macromolecules with high-arm density and hydrodynamic diameters between
      10 and 70 nm. 

PMID- 27027405
TI  - The autophagy-lysosomal system in subarachnoid haemorrhage.
AB  - The autophagy-lysosomal pathway is a self-catabolic process by which
      dysfunctional or unnecessary intracellular components are degraded by lysosomal
      enzymes. Proper function of this pathway is critical for maintaining cell
      homeostasis and survival. Subarachnoid haemorrhage (SAH) is one of the most
      devastating forms of stroke. Multiple pathogenic mechanisms, such as
      inflammation, apoptosis, and oxidative stress, are all responsible for brain
      injury and poor outcome after SAH. Most recently, accumulating evidence has
      demonstrated that the autophagy-lysosomal pathway plays a crucial role in the
      pathophysiological process after SAH. Appropriate activity of autophagy-lysosomal
      pathway acts as a pro-survival mechanism in SAH, while excessive self-digestion
      results in cell death after SAH. Consequently, in this review article, we will
      give an overview of the pathophysiological roles of autophagy-lysosomal pathway
      in the pathogenesis of SAH. And approaching the molecular mechanisms underlying
      this pathway in SAH pathology is anticipated, which may ultimately allow
      development of effective therapeutic strategies for SAH patients through
      regulating the autophagy-lysosomal machinery.

PMID- 27027406
TI  - Trends in serum total cholesterol and dietary fat intakes in New Zealand between
      1989 and 2009.
AB  - OBJECTIVE: To describe trends in serum cholesterol and dietary fat intakes for
      New Zealand adults between 1989 and 2008/09. METHODS: Serum total cholesterol
      concentrations and dietary fat intakes were analysed for 9,346 New Zealanders
      aged 15-98 years (52% women) who participated in three national surveys in 1989,
      1997 and 2008/09. RESULTS: Population mean serum cholesterol decreased from 6.15
      mmol/L in 1989 to 5.39 mmol/L in 2008/09. Mean saturated fat intake decreased
      from 15.9% of energy intake in 1989 to 13.1% in 2008/09. Between 1997 and
      2008/09, unsaturated fat intake increased and fat from butter and milk decreased.
      Older adults had the largest decrease in serum cholesterol (1.35 mmol/L).
      CONCLUSIONS: The decrease in serum cholesterol is substantially larger than
      reported for many other high-income countries, and occurred in parallel with
      changes in dietary fat intakes and, for older adults, increased use of
      cholesterol-lowering medications. IMPLICATION: Given the demonstrated role of
      reduced saturated fat intake on lowering serum cholesterol, and as population
      average serum cholesterol levels and saturated fat intakes exceed recommended
      levels, initiatives to further encourage reductions in saturated fat are
      imperative.

PMID- 27027407
TI  - Osteolytic and mixed cancer metastasis modulates collagen and mineral parameters
      within rat vertebral bone matrix.
AB  - Metastatic involvement in vertebral bone diminishes the mechanical integrity of
      the spine; however minimal data exist on the potential impact of metastases on
      the intrinsic material characteristics of the bone matrix. Thirty-four (34)
      female athymic rats were inoculated with HeLa (N = 17) or Ace-1 (N = 17) cancer
      cells lines producing osteolytic or mixed (osteolytic and osteoblastic)
      metastases, respectively. A maximum of 21 days was allowed between inoculation
      and rat sacrifice for vertebrae extraction. High performance liquid
      chromatography (HPLC) was utilized to determine modifications in collagen-I
      parameters such as proline hydroxylation and the formation of specific enzymatic
      and non-enzymatic (pentosidine) cross-links. Raman spectroscopy was used to
      determine relative changes in mineral crystallinity, mineral carbonation,
      mineral/collagen matrix ratio, collagen quality ratio, and proline hydroxylation.
      HPLC results showed significant increase in the formation of pentosidine and
      decrease in the formation of the enzymatic cross-link deoxy-pryridinoline within
      osteolytic bone compared to mixed bone. Raman results showed decreased
      crystallinity, increased carbonation, and collagen quality (aka 1660/1690 sub
      band) ratio with osteolytic bone compared to mixed bone and healthy controls
      along with an observed increase in proline hydroxylation with metastatic
      involvement. The mineral/matrix ratio decreased in both osteolytic and mixed bone
      compared to healthy controls. Quantifying modifications within the intrinsic
      characteristics of bone tissue will provide a foundation to assess the impact of
      current therapies on the material behavior of bone tissue in the metastatic spine
      and highlight targets for the development of new therapeutics and approaches for
      treatment. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res 34:2126-2136, 2016.

PMID- 27027409
TI  - Radical Polymerization of Vinyl Monomers in Porous Organic Cages.
AB  - The radical polymerization of vinyl monomers was performed in a tetrahedral imine
      linked organic cage with extrinsic porosity (CC3). Because of its dynamic and
      responsive packing structure, CC3 endowed the polymerization with specific
      behaviors. The adsorption of styrene triggered a change in the CC3 assembly,
      resulting in a monomer arrangement that was suitable for polymerization within
      the host matrix. The polymerization reaction was strongly dependent on the
      crystallinity of CC3 and was promoted by amorphization of the host in a
      cooperative manner, which is not possible with conventional rigid porous
      materials. Furthermore, CC3 can recognize the polarity of substrates, and thus
      polar monomers, such as methyl methacrylate and acrylonitrile, could not induce
      the structural changes in CC3 that are required for polymerization. This monomer
      specificity governed by the flexibility of CC3 is useful to the prevent
      incorporation of unfavorable monomers into the polymeric products.

PMID- 27027408
TI  - Regulation of iron acquisition responses in plant roots by a transcription
      factor.
AB  - The presented research hypothesis-driven laboratory exercise teaches advanced
      undergraduate students state of the art methods and thinking in an integrated
      molecular physiology context. Students understand the theoretical background of
      iron acquisition in the model plant Arabidopsis thaliana. They design a flowchart
      summarizing the key steps of the experimental approach. Students are made
      familiar with current techniques such as qPCR. Following their experimental
      outline, students grow Arabidopsis seedlings up to the age of six days under
      sufficient and deficient iron supply. The Arabidopsis plants are of two different
      genotypes, namely wild type and fit loss of function mutants. fit mutants lack
      the essential transcription factor FIT, required for iron acquisition and plant
      growth. Students monitor growth phenotypes and root iron reductase activity in a
      quantitative and qualitative manner. Then, students determine gene expression
      regulation of FIT, FRO2, and a reference gene by reverse transcription
      quantitative PCR (RT-qPCR). Finally, students interpet their results and build a
      model summarizing the connections between morphological, physiological and
      molecular iron deficiency responses. Learning outcomes and suggestions for
      integrating the course concept are explained. (c) 2016 by The International Union
      of Biochemistry and Molecular Biology, 44(5):438-449, 2016.

PMID- 27027410
TI  - Combination therapy of normobaric oxygen with hypothermia or ethanol modulates
      pyruvate dehydrogenase complex in thromboembolic cerebral ischemia.
AB  - Pyruvate dehydrogenase complex (PDH) is a brain mitochondrial matrix enzyme. PDH
      impairment after stroke is particularly devastating given PDH's critical role in
      the link between anaerobic and aerobic metabolism. This study evaluates the
      restoration of oxidative metabolism and energy regulation with a therapeutic
      combination of normobaric oxygen (NBO) plus either therapeutic hypothermia (TH)
      or ethanol. Sprague-Dawley rats were subjected to middle cerebral artery
      occlusion with an autologous embolus. One hour after occlusion, tissue-type
      plasminogen activator (t-PA) was administered alone or with NBO (60%), EtOH (1.0
      g/kg), or TH (33 degrees C), either singly or in combination. Neurological
      deficit score and infarct volume were assessed 24 hr after t-PA-induced
      reperfusion. PDH activity and reactive oxygen species (ROS) levels were measured
      3 and 24 hr after t-PA. Western blotting was used to detect PDH and pyruvate
      dehydrogenase kinase (PDK) protein expression. After t-PA in ischemic rats, NBO
      combined with TH or EtOH most effectively decreased infarct volume and
      neurological deficit. The combined therapies produced greater increases in PDH
      activity and protein expression as well as greater decreases in PDK expression.
      Compared with the monotherapeutic approaches, the combined therapies provided the
      most significant declines in ROS generation. Reperfusion with t-PA followed by
      60% NBO improves the efficacy of EtOH or TH in neuroprotection by ameliorating
      oxidative injury and improving PDH regulation. Comparable neuroprotective effects
      were found when treating with either EtOH or TH, suggesting a similar mechanism
      of neuroprotection and the possibility of substituting EtOH for TH in clinical
      settings. (c) 2016 Wiley Periodicals, Inc.

PMID- 27027411
TI  - Catalytic Scanning Probe Nanolithography (cSPL): Control of the AFM Parameters in
      Order to Achieve Sub-100-nm Spatially Resolved Epoxidation of Alkenes Grafted
      onto a Surface.
AB  - Scanning probe lithography (SPL) appears to be a reliable alternative to the use
      of masks in traditional lithography techniques as it offers the possibility of
      directly producing specific chemical functionalities with nanoscale spatial
      control. We have recently extend the range of applications of catalytic SPL
      (cSPL) by introducing a homogeneous catalyst immobilized on the apex of a
      scanning probe. Here we investigate the importance of atomic force microscopy
      (AFM) physical parameters (applied force, writing speed, and interline distance)
      on the resultant chemical activity in this cSPL methodology through the direct
      topographic observation of nanostructured surfaces. Indeed, an alkene-terminated
      self-assembled monolayer (alkene-SAM) on a silicon wafer was locally epoxidized
      using a scanning probe tip with a covalently grafted manganese complex bearing
      the 1,4,7-triazacyclononane macrocycle as the ligand. In a post-transformation
      process, N-octylpiperazine was covalently grafted to the surface via a selective
      nucleophilic ring-opening reaction. With this procedure, we could write various
      patterns on the surface with high spatial control. The catalytic AFM probe thus
      appears to be very robust because a total area close to 500 MUm(2) was patterned
      without any noticeable loss of catalytic activity. Finally, this methodology
      allowed us to reach a lower lateral line resolution down to 40 nm, thus being
      competitive and complementary to the other nanolithographical techniques for the
      nanostructuration of surfaces.

PMID- 27027412
TI  - Ledipasvir-Sofosbuvir: A Once-Daily Oral Treatment Option for Chronic Hepatitis C
      Virus Genotype 1 Infection.
AB  - Chronic hepatitis C virus (HCV) genotype 1 historically has been the most
      difficult to treat HCV genotype, and patients infected with this genotype had
      been previously treated with interferon-based therapy. In recent years, however,
      treatment options for chronic HCV infection have rapidly changed to an all-oral
      regimen. Ledipasvir-sofosbuvir is an oral fixed-dose (ledipasvir 90 mg-sofosbuvir
      400 mg) combination of two direct-acting antiviral drugs. Four phase 3 clinical
      trials (ION-1-4) evaluated ledipasvir-sofosbuvir with and without ribavirin in
      patients with HCV genotype 1. High rates of sustained virologic response (SVR)
      occurred with ledipasvir-sofosbuvir alone in treatment-naive and treatment
      experienced patients without cirrhosis as well as in treatment-naive patients
      with cirrhosis when administered for 12 weeks. In treatment-experienced patients
      with cirrhosis, 24 weeks of ledipasvir-sofosbuvir was also highly effective.
      Furthermore, treatment-naive patients without cirrhosis (particularly those with
      HCV RNA serum concentrations < 6 million IU/ml) can achieve a similar SVR with
      only 8 weeks of therapy. Similarly, in patients coinfected with human
      immunodeficiency virus and HCV genotype 1 who were treated with ledipasvir
      sofosbuvir for 12 weeks, a high SVR was observed in those with and without
      cirrhosis as well as treatment-naive and treatment-experienced patients.
      Ledipasvir-sofosbuvir is well tolerated, with fatigue, headache, nausea,
      diarrhea, and insomnia being the most common adverse effects, which are typically
      mild to moderate in nature. This combination antiviral can be taken with or
      without food. Key factors to consider when prescribing ledipasvir-sofosbuvir are
      drug interactions including those mediated by the P-glycoprotein transporter and
      increased pH, cost of the drug or insurance coverage, comorbid conditions, and
      patient and provider preferences. Postmarketing experience and ongoing clinical
      trials will further define the safety and role of ledipasvir-sofosbuvir in the
      treatment of HCV genotype 1.

PMID- 27027413
TI  - Focal loss volume of ganglion cell complex in diabetic neuropathy.
AB  - BACKGROUND: The aim was to investigate the relationship between diabetic
      peripheral neuropathy (DPN) and abnormalities in ganglion cell complex (GCC);
      specifically, focal loss volume (FLV) and global loss volume (GLV). METHODS: The
      ganglion cell complex was evaluated using optical coherence tomography on 193
      individuals (84 with type 1 diabetes, 67 with type 2 diabetes and 42 without
      diabetes). In those with diabetes, 88 had diabetes but no diabetic retinopathy
      (no DR group) and 63 had diabetes with diabetic retinopathy (DR group). Seventeen
      individuals in the no DR group and 27 in the DR group had diabetic peripheral
      neuropathy according to the neuropathy disability score (NDS). The probability of
      FLV and GLV being abnormal was determined. Forty four individuals had diabetic
      peripheral neuropathy (NDS of three or greater). Binary logistic regression
      analysis was performed, adjusting for the presence of diabetic retinopathy, age,
      sex, type of diabetes, duration of diabetes and HbA1c levels. RESULTS: Twenty
      five per cent of individuals with diabetic peripheral neuropathy had abnormal FLV
      compared to 11 per cent of those with diabetes but no diabetic peripheral
      neuropathy and five per cent in the control group (p = 0.011). Fourteen per cent
      of individuals with diabetic peripheral neuropathy, 10 per cent without diabetic
      peripheral neuropathy and two per cent in the control group had abnormal GLV (p =
      0.185). For every unit increase in the neuropathy disability score, the odds of
      having an abnormal FLV increased by a factor of 1.25 (p = 0.007), after adjusting
      for potentially confounding factors. Abnormal GCC FLV is an independent predictor
      of diabetic neuropathy, (odds ratio = 2.94, 95 per cent CI [1.16, 7.40], p =
      0.023). CONCLUSION: Diabetic peripheral neuropathy is associated with abnormal
      GCC FLV at the macula, which is independent of diabetic retinopathy, age, sex,
      type of diabetes, duration of diabetes and HbA1c levels. An abnormality in GCC
      FLV is an independent predictor of diabetic peripheral neuropathy.

PMID- 27027414
TI  - The future of the Roux-en-Y gastric bypass.
AB  - Archaic surgical procedures such as the jejunoileal bypass, vertical banded
      gastroplasty and duodenal switch have contributed to the current best practice of
      Roux-en-Y gastric bypass (RYGB) procedure for the treatment of obesity and its
      consequences. Despite this, RYGB has been blighted with late occurring adverse
      events such as severe malnutrition, marginal ulcer and reactive hypoglycemia.
      Despite this, RYGB has given us an opportunity to examine the effect of surgery
      on gut hormones and the impact on metabolic syndrome which in turn has allowed us
      to carry out a lower impact but equally, if not more effective, procedure - the
      vertical sleeve gastrectomy (VSG). We examine the benefits of sleeve gastrectomy
      from the less challenging technical aspect to the effect on obesity and its
      metabolic syndrome long-term and have concluded that sleeve gastrectomy is
      possibly the next current best practice. 

PMID- 27027415
TI  - Technique for reliable sentinel node biopsy in squamous cell carcinomas of the
      floor of mouth.
AB  - BACKGROUND: Applicability of sentinel node biopsy (SNB) for tumors of the floor
      of mouth (FOM) is controversial. METHODS: Prospective evaluation of the accuracy
      of gamma-probe-guided superselective neck dissection of the preglandular triangle
      of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative
      lymphoscintigraphy and single photon emission CT (SPECT)/CT. RESULTS: In total,
      22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on
      lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%)
      were only detected intraoperatively. In unilateral tumors, 20% were
      contralateral, and, in midline tumors, 93% showed bilateral level I sentinel
      lymph nodes. The false-negative rate was 8.3%, the negative predictive value was
      96.4%, and the false-omission rate was 3.6%. The ultimate neck control rate,
      including salvage treatment, was 100%. CONCLUSION: SNB in FOM can be reliably
      performed using the presented surgical technique. Level I exploration,
      bilaterally in midline tumors, is mandatory irrespective of the visualization of
      sentinel lymph nodes in other levels. (c) 2016 Wiley Periodicals, Inc. Head Neck
      38: 1367-1372, 2016.

PMID- 27027417
TI  - Surveillance rates for hepatocellular carcinoma among patients with cirrhosis,
      chronic hepatitis B, and chronic hepatitis C based on Japanese claims database.
AB  - AIM: Surveillance is recommended for patients with risk of hepatocellular
      carcinoma (HCC) such as viral hepatitis and liver cirrhosis (LC). Although
      populations are at higher risk in Asia, surveillance rates have not been
      evaluated in those countries. Therefore, we aimed to examine surveillance rates
      for HCC and to compare predictors for surveillance among each type of liver
      disease in Japan. METHODS: We carried out an observational study using the
      medical claims data of Japan. A total of 4713 patients who were diagnosed with
      LC, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection were followed
      for 12 months. We described surveillance rates in patients with HBV or HCV
      infection or non-viral LC and evaluated potential predictors for follow-up
      surveillance among them by using multivariable logistic regression analysis, in
      which we set explanatory variables as sex, age, medical facility, HBV or HCV
      infection, and LC. RESULTS: The HCC surveillance rate during follow-up was 42.3%
      among patients with chronic viral hepatitis, 56.5% with viral cirrhosis and
      26.0%, with non-viral LC. Significant predictors for follow-up surveillance were
      presence of LC and hospital visits. Hepatitis B virus-infected patients aged <50
      years and HCV-infected patients aged >=50 years were more likely to undergo
      exams, that is, different tendencies between HBV and HCV patients were shown.
      CONCLUSIONS: Follow-up surveillance for HCC was not adequately carried out among
      patients at risk for HCC in Japan, despite of recommendation in guidelines. In
      future, methodological research might be needed to increase surveillance rates
      for HCC in patients with chronic hepatitis or those who received treatment at a
      clinic.

PMID- 27027416
TI  - Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra
      Abdominal Infection.
AB  - BACKGROUND: Obesity and commonly associated comorbidities are known risk factors
      for the development of infections. However, the intensity and duration of
      antimicrobial treatment are rarely conditioned on body mass index (BMI). In
      particular, the influence of obesity on failure of antimicrobial treatment for
      intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is
      associated with recurrent infectious complications in patients treated for IAI.
      METHODS: Five hundred eighteen patients randomized to treatment in the Surgical
      Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial
      were evaluated. Patients were stratified by obese (BMI >=30) versus non-obese
      (BMI>=30) status. Descriptive comparisons were performed using Chi-square test,
      Fisher exact test, or Wilcoxon rank-sum tests as appropriate. Multivariable
      logistic regression using a priori selected variables was performed to assess the
      independent association between obesity and treatment failure in patients with
      IAI. RESULTS: Overall, 198 (38.3%) of patients were obese (BMI >=30) versus 319
      (61.7%) who were non-obese. Mean antibiotic d and total hospital d were similar
      between both groups. Unadjusted outcomes of surgical site infection (9.1% vs.
      6.9%, p = 0.36), recurrent intra-abdominal infection (16.2% vs. 13.8, p = 0.46),
      death (1.0% vs. 0.9%, p = 1.0), and a composite of all complications (25.3% vs.
      19.8%, p = 0.14) were also similar between both groups. After controlling for
      appropriate demographics, comorbidities, severity of illness, treatment group,
      and duration of antimicrobial therapy, obesity was not independently associated
      with treatment failure (c-statistic: 0.64). CONCLUSIONS: Obesity is not
      associated with antimicrobial treatment failure among patients with IAI. These
      results suggest that obesity may not independently influence the need for longer
      duration of antimicrobial therapy in treatment of IAI versus non-obese patients.

PMID- 27027418
TI  - Protection of Nitrate-Reducing Fe(II)-Oxidizing Bacteria from UV Radiation by
      Biogenic Fe(III) Minerals.
AB  - Due to the lack of an ozone layer in the Archean, ultraviolet radiation (UVR)
      reached early Earth's surface almost unattenuated; as a consequence, a
      terrestrial biosphere in the form of biological soil crusts would have been
      highly susceptible to lethal doses of irradiation. However, a self-produced
      external screen in the form of nanoparticular Fe(III) minerals could have
      effectively protected those early microorganisms. In this study, we use viability
      studies by quantifying colony-forming units (CFUs), as well as Fe(II) oxidation
      and nitrate reduction rates, to show that encrustation in biogenic and abiogenic
      Fe(III) minerals can protect a common soil bacteria such as the nitrate-reducing
      Fe(II)-oxidizing microorganisms Acidovorax sp. strain BoFeN1 and strain 2AN from
      harmful UVC radiation. Analysis of DNA damage by quantifying cyclobutane
      pyrimidine dimers (CPD) confirmed the protecting effect by Fe(III) minerals. This
      study suggests that Fe(II)-oxidizing microorganisms, as would have grown in
      association with mafic and ultramafic soils/outcrops, would have been able to
      produce their own UV screen, enabling them to live in terrestrial habitats on
      early Earth.

PMID- 27027419
TI  - Development and interrater reliability of the UK Mental Health Triage Scale.
AB  - Mental health triage scales are clinical tools used at point of entry to
      specialist mental health service to provide a systematic way of categorizing the
      urgency of clinical presentations, and determining an appropriate service
      response and an optimal timeframe for intervention. The aim of the present study
      was to test the interrater reliability of a mental health triage scale developed
      for use in UK mental health triage and crisis services. An interrater reliability
      study was undertaken. Triage clinicians from England and Wales (n = 66) used the
      UK Mental Health Triage Scale (UK MHTS) to rate the urgency of 21 validated
      mental health triage scenarios derived from real occasions of triage. Interrater
      reliability was calculated using Kendall's coefficient of concordance (w) and
      intraclass correlation coefficient (ICC) statistics. The average ICC was 0.997
      (95% confidence interval (CI): 0.996-0.999 (F (20, 1300) = 394.762, P < 0.001).
      The single measure ICC was 0.856 (95% CI: 0.776-0.926 (F (20, 1300) = 394.762, P
      < 0.001). The overall Kendall's w was 0.88 (P < 0.001). The UK MHTS shows
      substantial levels of interrater reliability. Reliable mental health triage
      scales employed within effective mental health triage systems offer possibilities
      for not only improved patient outcomes and experiences, but also for efficient
      use of finite specialist mental health services. 

PMID- 27027421
TI  - Beat that Word: How Listeners Integrate Beat Gesture and Focus in Multimodal
      Speech Discourse.
AB  - Communication is facilitated when listeners allocate their attention to important
      information (focus) in the message, a process called "information structure."
      Linguistic cues like the preceding context and pitch accent help listeners to
      identify focused information. In multimodal communication, relevant information
      can be emphasized by nonverbal cues like beat gestures, which represent rhythmic
      nonmeaningful hand movements. Recent studies have found that linguistic and
      nonverbal attention cues are integrated independently in single sentences.
      However, it is possible that these two cues interact when information is embedded
      in context, because context allows listeners to predict what information is
      important. In an ERP study, we tested this hypothesis and asked listeners to view
      videos capturing a dialogue. In the critical sentence, focused and nonfocused
      words were accompanied by beat gestures, grooming hand movements, or no gestures.
      ERP results showed that focused words are processed more attentively than
      nonfocused words as reflected in an N1 and P300 component. Hand movements also
      captured attention and elicited a P300 component. Importantly, beat gesture and
      focus interacted in a late time window of 600-900 msec relative to target word
      onset, giving rise to a late positivity when nonfocused words were accompanied by
      beat gestures. Our results show that listeners integrate beat gesture with the
      focus of the message and that integration costs arise when beat gesture falls on
      nonfocused information. This suggests that beat gestures fulfill a unique
      focusing function in multimodal discourse processing and that they have to be
      integrated with the information structure of the message. 

PMID- 27027422
TI  - What is Personality?

PMID- 27027420
TI  - Frontal Monitoring and Parietal Evidence: Mechanisms of Error Correction.
AB  - When we respond to a stimulus, our decisions are based not only on external
      stimuli but also on our ongoing performance. If the response deviates from our
      goals, monitoring and decision-making brain areas interact so that future
      behavior may change. By taking advantage of natural variation in error salience,
      as measured by the RT taken to correct an error (RTEC), here we argue that an
      evidence accumulation framework provides a potential underlying mechanism for
      this variable process of error identification and correction, as evidenced by
      covariation of frontal monitoring and parietal decision-making processes. We
      study two early EEG signals linked to monitoring within medial PFC-the error
      related negativity (ERN) and frontocentral theta activity-and a third EEG signal,
      the error positivity (Pe), that is thought to share the same parietal substrates
      as a signal (the P3b) proposed to reflect evidence accumulation. As predicted,
      our data show that on slow RTEC trials, frontal monitoring resources are less
      strongly employed, and the latency of the Pe is longer. Critically, the speed of
      the RTEC also covaries with the magnitude of subsequent neural (intertrial alpha
      power) and behavioral (post-error slowing) adjustments following the correction.
      These results are synthesized to describe a timing diagram for adaptive decision
      making after errors and support a potential evidence accumulation mechanism in
      which error signaling is followed by rapid behavioral adjustments. 

PMID- 27027423
TI  - Electrophoretic Deposition for Cholesteric Liquid-Crystalline Devices with Memory
      and Modulation of Reflection Colors.
AB  - The first design strategy that allows both memorization and modulation of the
      liquid-crystalline reflection color is reported. Electrophoretic deposition of a
      tailored ionic chiral dopant is key to realizing this unprecedented function,
      which may pave the way for the development of full-color e-paper that can operate
      without the need of color filters. 

PMID- 27027424
TI  - Spontaneous resolution of post-delivery or post-abortion uterine artery
      pseudoaneurysm: A report of three cases.
AB  - Post-delivery/-abortion uterine artery pseudoaneurysm (UAP) sometimes causes life
      threatening bleeding, requiring transarterial embolization (TAE). It is unclear
      whether some UAP resolve spontaneously. In three patients, UAP resolved
      spontaneously without TAE. Case 1 was after vacuum delivery with slight bleeding:
      at day 5 post-partum, a yin-yang sign on Color Doppler and an enhanced
      intrauterine sac-like structure were observed, leading to the diagnosis of UAP,
      which disappeared at 4 weeks post-partum. Case 2 was after vacuum delivery with
      manual placental removal and was asymptomatic: a hypoechoic intrauterine mass
      with a yin-yang sign were observed during a post-partum routine check-up and the
      intrauterine flow disappeared at 4 weeks post-partum. Case 3 was after dilatation
      and curettage in the first trimester with slight bleeding: UAP was detected at 4
      weeks post-abortion, which disappeared at 6 weeks post-abortion. All three cases
      had a small UAP (diameter: 10-15 mm) and low-level or no symptoms. Some UAP may
      resolve spontaneously and, thus, may not require TAE.

PMID- 27027425
TI  - The velocity of antihypertensive effects of seven angiotensin II receptor
      blockers determined by home blood pressure measurements.
AB  - BACKGROUND: We aimed to examine the blood pressure (BP)-lowering effect and the
      time to attain the maximal antihypertensive effect (stabilization time) of
      several angiotensin II receptor blockers (ARBs) based on home BP measurements.
      METHODS: We surveyed consecutive newly diagnosed, untreated patients with
      hypertension who started the treatment with a mid-level dose of one of seven ARBs
      (losartan 50 mg, telmisartan 40 mg, candesartan 8 mg, olmesartan 20 mg, valsartan
      80 mg, irbesartan 100 mg, or azilsartan 20 mg). All study participants measured
      home BP in the morning for at least 1 week during an untreated period and 4 weeks
      during the treatment period. RESULTS: Age, the proportion of men, and baseline
      home BP levels did not differ significantly between groups (total n = 232; age,
      62.2 years; 50.9% men; home SBP/DBP, 151.6/90.0 mmHg). Significant differences in
      the BP-lowering effect and the stabilization time between ARBs were observed (P
      <= 0.02). The extent of BP-lowering effects of azilsartan 20 mg was significantly
      greater than that of valsartan 80 mg or irbesartan 100 mg (15.3 vs. 7.9 or 8.2
      mmHg, respectively P <= 0.03). The stabilization time of losartan for home SBP
      was significantly longer than that of valsartan, irbesartan, or azilsartan (22.8
      vs. 7.1, 4.7, or 7.1 days, respectively, P <= 0.01). CONCLUSION: The maximum
      effect and the stabilization time differed among ARBs used at the mid-level dose
      in Japan. An ARB should be chosen based on its desired characteristics.

PMID- 27027426
TI  - Hypovitaminosis D and orthostatic hypotension: a systematic review and meta
      analysis.
AB  - OBJECTIVES: Orthostatic hypotension is a common condition among older adults and
      is associated with a range of deleterious outcomes. Recently, interest has
      developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a
      potential risk factor for orthostatic hypotension. We conducted a systematic
      review and meta-analysis examining the association of orthostatic hypotension
      between study participants with and without hypovitaminosis D, including the
      adjustment of potential confounders (age, sex, BMI, renal function,
      comorbidities, seasonality, use of antihypertensive medications, and
      supplementation with cholecalciferol). METHODS: A systematic literature search of
      major electronic databases from inception until 09/2015 was made for articles
      providing data on orthostatic hypotension and hypovitaminosis D. A random effects
      meta-analysis of cross-sectional studies investigating orthostatic hypotension
      prevalence comparing participants with vs. those without hypovitaminosis D was
      undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs).
      RESULTS: Of 317 initial hits, five cross-sectional studies were meta-analysed
      including 3646 participants (1270 with hypovitaminosis D and 2376 without). The
      participants with hypovitaminosis D had a higher prevalence of orthostatic
      hypotension (OR = 1.88; 95% CI: 1.25-2.84; I = 68%) that was not affected by
      adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13
      3.68; I = 73%). People with orthostatic hypotension had significantly reduced
      serum vitamin D concentrations (standardized mean difference = -0.42; 95% CI: 
      0.72 to -0.12). One longitudinal study confirmed the association between
      hypovitaminosis D and orthostatic hypotension. CONCLUSION: Our meta-analysis
      highlights that hypovitaminosis D is associated with orthostatic hypotension,
      independent of potential confounders. Further longitudinal studies and clinical
      trials are required to confirm these findings.

PMID- 27027428
TI  - A multi-source feedback tool for measuring a subset of Pediatrics Milestones.
AB  - BACKGROUND: The Pediatrics Milestones Assessment Pilot employed a new multisource
      feedback (MSF) instrument to assess nine Pediatrics Milestones among interns and
      subinterns in the inpatient context. OBJECTIVE: To report validity evidence for
      the MSF tool for informing milestone classification decisions. METHODS: We
      obtained MSF instruments by different raters per learner per rotation. We present
      evidence for validity based on the unified validity framework. RESULTS: One
      hundred and ninety two interns and 41 subinterns at 18 Pediatrics residency
      programs received a total of 1084 MSF forms from faculty (40%), senior residents
      (34%), nurses (22%), and other staff (4%). Variance in ratings was associated
      primarily with rater (32%) and learner (22%). The milestone factor structure fit
      data better than simpler structures. In domains except professionalism, ratings
      by nurses were significantly lower than those by faculty and ratings by other
      staff were significantly higher. Ratings were higher when the rater observed the
      learner for longer periods and had a positive global opinion of the learner.
      Ratings of interns and subinterns did not differ, except for ratings by senior
      residents. MSF-based scales correlated with summative milestone scores.
      CONCLUSION: We obtain moderately reliable MSF ratings of interns and subinterns
      in the inpatient context to inform some milestone assignments.

PMID- 27027427
TI  - Intrinsic Brain Connectivity Following Long-Term Treatment with Methylphenidate
      in Children with Attention-Deficit/Hyperactivity Disorder.
AB  - INTRODUCTION: Although widely used for the treatment of attention
      deficit/hyperactivity disorder (ADHD) across the life span, the effects of
      methylphenidate (MPH) on the brain are not completely understood. Functional
      neuroimaging techniques may help increase knowledge about the mechanisms of MPH
      action. OBJECTIVE: To evaluate changes in functional connectivity patterns of the
      default mode network (DMN) in children with ADHD following long-term treatment
      with MPH. METHODS: Twenty-three right-handed treatment-naive boys with ADHD
      underwent a protocol of intrinsic functional connectivity before and after 6
      months of treatment with MPH. Functional connectivity was analyzed using a region
      of interest (ROI) approach and independent component analysis (ICA). RESULTS: ROI
      analyses showed no significant changes in connectivity between regions of the DMN
      following treatment, with a relatively small increase in the anterior-posterior
      connectivity of the network. ICA revealed a significant increase in connectivity
      between the left putamen and the DMN (p < 0.001, corrected). There was a
      correlation between the reduction of symptoms and the increased connectivity
      between the putamen and the DMN after treatment (rho = -0.65, p = 0.017).
      CONCLUSION: Dysfunctions in cortical-subcortical circuits have often been
      associated with the pathophysiology of ADHD. Our findings suggest that effective
      treatment with MPH in children with ADHD may affect brain functioning by
      increasing connectivity between the DMN and subcortical nuclei.

PMID- 27027429
TI  - Prognostic value of aberrant promoter hypermethylation of tumor-related genes in
      early-stage head and neck cancer.
AB  - Staging and pathological grading are useful, but imperfect predictors of
      recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly,
      molecular biomarkers that predict the risk of recurrence are necessary to improve
      clinical outcomes. The methylation statuses of the promoters of 11 tumor-related
      genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST,
      and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation
      specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E
      cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2
      (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was
      lower in patients with 6-11 methylated genes than in those with 0-5 methylated
      genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards
      analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated
      with poor survival, with hazard ratios of 4.474 (95% CI, 1.241-16.124). In a
      joint analysis of these four genes, patients with 2-4 methylated genes had a
      significantly lower survival rate than those with 0-1 methylated genes in early
      stage HNSCC. Importantly, the methylation of some genes was closely related to
      poor prognosis in early-stage HNSCC, providing strong evidence that these
      hypermethylated genes are valuable biomarkers for prognostic evaluation. 

PMID- 27027430
TI  - Differentiation inducing factor 3 mediates its anti-leukemic effect through ROS
      dependent DRP1-mediated mitochondrial fission and induction of caspase
      independent cell death.
AB  - Differentiation-inducing factor (DIF) defines a group of chlorinated hexaphenones
      that orchestrate stalk-cell differentiation in the slime mold Dictyostelium
      discoideum (DD). DIF-1 and 3 have also been reported to have tumor inhibiting
      properties; however, the mechanisms that underlie the effects of these compounds
      remain poorly defined. Herein, we show that DIF-3 rapidly triggers Ca2+ release
      and a loss of mitochondrial membrane potential (MMP) in the absence of cytochrome
      c and Smac release and without caspase activation. Consistently with these
      findings, we also detected no evidence of apoptosis in cells treated with DIF-3
      but instead found that this compound induced autophagy. In addition, DIF-3
      promoted mitochondrial fission in K562 and HeLa cells, as assessed by electron
      and confocal microscopy analysis. Importantly, DIF-3 mediated the phosphorylation
      and redistribution of dynamin-related protein 1 (DRP1) from the cytoplasmic to
      the microsomal fraction of K562 cells. Pharmacological inhibition or siRNA
      silencing of DRP1 not only inhibited mitochondrial fission but also protected
      K562 cells from DIF-3-mediated cell death. Furthermore, DIF-3 potently inhibited
      the growth of imatinib-sensitive and imatinib-resistant K562 cells. It also
      inhibited tumor formation in athymic mice engrafted with an imatinib-resistant
      CML cell line. Finally, DIF-3 exhibited a clear selectivity toward CD34+ leukemic
      cells from CML patients, compared with CD34- cells. In conclusion, we show that
      the potent anti-leukemic effect of DIF-3 is mediated through the induction of
      mitochondrial fission and caspase-independent cell death. Our findings may have
      important therapeutic implications, especially in the treatment of tumors that
      exhibit defects in apoptosis regulation. 

PMID- 27027431
TI  - p21-activated kinase 1 (PAK1) expression correlates with prognosis in solid
      tumors: A systematic review and meta-analysis.
AB  - p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) expression appears to be
      predictive of prognosis in various solid tumors, though the evidence is not yet
      conclusive. We therefore performed a meta-analysis to explore the relationship
      between PAK1 and prognosis in patients with solid tumors. Relevant publications
      were searched in several widely used databases, and 15 studies (3068 patients)
      were included in the meta-analysis. Pooled hazard ratios (HRs) and 95% confidence
      intervals (CIs) were calculated to evaluate the strength of the association
      between PAK1 and prognosis. Associations between PAK1 expression and prognosis
      were observed for overall survival (HR = 2.81, 95% CI = 1.07-7.39) and disease
      specific survival (HR = 2.15, 95% CI = 1.47-3.16). No such association was
      detected for time to tumor progression (HR = 1.78, 95% CI = 0.99-3.21).Our meta
      analysis thus indicates that PAK1 expression may be a predictive marker of
      overall survival and disease-specific survival in patients with solid tumors. 

PMID- 27027433
TI  - Xenopatients show the need for precision medicine approach to chemotherapy in
      ovarian cancer.
AB  - Platinum-based chemotherapy is the recommended first-line treatment for high
      grade serous (HGS) epithelial ovarian cancer (EOC). However, most patients
      relapse because of platinum refractory/resistant disease. We aimed at assessing
      whether other drugs, commonly used to treat relapsed HGS-EOC and poorly active in
      this clinical setting, might be more effective against chemotherapy-naive
      cancers. We collected couples of HGS-EOC samples from the same patients before
      and after neo-adjuvant platinum-based chemotherapy. Samples were propagated as
      Patient Derived Xenografts (PDXs) in immunocompromised mice ("xenopatients").
      Xenopatients were treated in parallel with carboplatin, gemcitabine, pegylated
      liposomal doxorubicin (PLD) and trabectedin. PDXs derived from a naive HSG-EOC
      showed responsiveness to carboplatin, trabectedin and gemcitabine. The PDXs
      propagated from a tumor mass of the same patient, grown after carboplatin
      therapy, did no longer respond to trabectedin and gemcitabine and showed
      heterogeneous response to carboplatin. In line, the patient experienced
      clinically platinum-sensitivity first and then discordant responses of different
      tumor sites to platinum re-challenge. Loss of PDX responsiveness to drugs was
      associated with 4-fold increase of NR2F2 gene expression. PDXs from another naive
      tumor showed complete response to PLD, which was lost in the PDXs derived from a
      mass grown in the same patient after platinum-based chemotherapy. This patient
      showed platinum refractoriness and responded poorly to PLD as second-line
      treatment. PDX response to PLD was associated with high expression of TOP2A
      protein. PDXs demonstrated that chemotherapy-naive HGS-EOC might display
      susceptibility to agents not used commonly as first line treatment. Data suggest
      the importance of personalizing also chemotherapy. 

PMID- 27027432
TI  - The dynamics of gene expression changes in a mouse model of oral tumorigenesis
      may help refine prevention and treatment strategies in patients with oral cancer.
AB  - A better understanding of the dynamics of molecular changes occurring during the
      early stages of oral tumorigenesis may help refine prevention and treatment
      strategies. We generated genome-wide expression profiles of microdissected normal
      mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of
      oral tumorigenesis. Genes differentially expressed between tumor and normal
      mucosa defined the "tumor gene set" (TGS), including 4 non-overlapping gene
      subsets that characterize the dynamics of gene expression changes through
      different stages of disease progression. The majority of gene expression changes
      occurred early or progressively. The relevance of these mouse gene sets to human
      disease was tested in multiple datasets including the TCGA and the Genomics of
      Drug Sensitivity in Cancer project. The TGS was able to discriminate oral
      squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets.
      The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8
      mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early
      changes observed in the 4-NQO model were associated with a trend toward a shorter
      oral cancer-free survival in patients with oral preneoplasia that was not seen in
      multivariate analysis. Progressive changes observed in the 4-NQO model were
      associated with an increased sensitivity to 4 different MEK inhibitors in a panel
      of 51 squamous cell carcinoma cell lines of the areodigestive tract. In
      conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK
      inhibition may be relevant to prevention and treatment of a specific molecularly
      defined subgroup of OSCC.

PMID- 27027434
TI  - Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration
      and invasion by targeting SMAD1 in hepatocellular carcinoma.
AB  - Twist1 is well known to induce epithelial-mesenchymal transition (EMT) and
      promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and
      are associated with metastasis in hepatocellular carcinoma (HCC). In the present
      study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly
      downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell
      lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1).
      miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the
      promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both
      gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed
      EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors
      derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant
      reduction in tumorigenicity compared with the control group. Subsequent
      investigation revealed that miR-26b-5p directly inhibited SMAD family member 1
      (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1
      inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human
      HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely
      correlated with SMAD1 expression as well as metastasis. CONCLUSION: miR-26b-5p
      suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting
      SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b
      5p in anti-HCC therapy.

PMID- 27027435
TI  - Functional characterization and anti-cancer action of the clinical phase II
      cardiac Na+/K+ ATPase inhibitor istaroxime: in vitro and in vivo properties and
      cross talk with the membrane androgen receptor.
AB  - Sodium potassium pump (Na+/K+ ATPase) is a validated pharmacological target for
      the treatment of various cardiac conditions. Recent published data with Na+/K+
      ATPase inhibitors suggest a potent anti-cancer action of these agents in multiple
      indications. In the present study, we focus on istaroxime, a Na+/K+ ATPase
      inhibitor that has shown favorable safety and efficacy properties in cardiac
      phase II clinical trials. Our experiments in 22 cancer cell lines and in prostate
      tumors in vivo proved the strong anti-cancer action of this compound. Istaroxime
      induced apoptosis, affected the key proliferative and apoptotic mediators c-Myc
      and caspase-3 and modified actin cystoskeleton dynamics and RhoA activity in
      prostate cancer cells. Interestingly, istaroxime was capable of binding to mAR, a
      membrane receptor mediating rapid, non-genomic actions of steroids in prostate
      and other cells. These results support a multi-level action of Na+/K+ ATPase
      inhibitors in cancer cells and collectively validate istaroxime as a strong re
      purposing candidate for further cancer drug development. 

PMID- 27027436
TI  - Association of genetic variants in lncRNA H19 with risk of colorectal cancer in a
      Chinese population.
AB  - OBJECTIVE: The long non-coding RNA (lncRNA) gene, H19, has been involving in
      multiple biological functions, which also plays a vital role in colorectal cancer
      carcinogenesis. However, the association between genetic variants in H19 and
      colorectal cancer susceptibility has not been reported. In this study, we aim to
      explore whether H19 polymorphisms are related to the susceptibility of colorectal
      cancer. METHODS: We conducted a case-control study to evaluate the association
      between four selected single nucleotide polymorphisms (SNPs) (rs2839698,
      rs3024270, rs217727, and rs2735971) in H19 and the risk of colorectal cancer in a
      Chinese population. RESULTS: We found that individuals with rs2839698 A allele
      had a significantly increased risk of colorectal cancer, compared to those
      carrying G allele [odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.05
      1.36 in additive model]. Further stratified analyses revealed that colon tumor
      site, well differentiated grade and Duke's stage of C/D were significantly
      associated with colorectal cancer risk (P < 0.05). Additionally, bioinformatic
      analysis showed that rs2839698 may change the crucial folding structures and
      alter the target microRNAs of H19. CONCLUSIONS: Our results provided the evidence
      that rs2839698 in H19 was associated with elevated risk of colorectal cancer,
      which may be a potential biomarker for predicting colorectal cancer
      susceptibility.

PMID- 27027437
TI  - Proper hepatic pedicle clamping during hepatectomy is associated with improved
      postoperative long-term prognosis in patients with AJCC stage IIIB hepatocellular
      carcinoma.
AB  - Intermittent hepatic pedicle clamping (HPC) is often performed during
      hepatectomy. Whether it affects the long-term prognosis of hepatocellular
      carcinoma (HCC) patients is still controversial. This study evaluated the impact
      of HPC in patients with different stages of HCC. The study included 1401 patients
      who underwent hepatectomy in the primary cohort with 129 AJCC stage IIIB HCC
      patients; there were 80 AJCC stage IIIB HCC patients in the validation cohort. In
      each cohort, patients were placed in the long-term HPC (LTHPC) group or the short
      term HPC (STHPC) group based on the cut-off time of HPC estimated by the receiver
      operating characteristic (ROC) curve. Although HPC did not show significant
      effects on the prognosis of stage I-IIIA HCC patients in the primary cohort, 1-,
      3-, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates of
      stage IIIB HCC patients who received LTHPC (HPC time > 12 minutes) were
      significantly higher than those with STHPC (HPC time <= 12 minutes or received no
      HPC), similar in the validation cohort. Multivariate analysis demonstrated HPC
      time was an independent protective factor for RFS and OS in stage IIIB HCC
      patients. Herein, we report that proper HPC improved the postoperative prognosis
      of stage IIIB HCC patients and served as an independent protective factor. 

PMID- 27027438
TI  - BM microenvironmental protection of CML cells from imatinib through Stat5/NF
      kappaB signaling and reversal by Wogonin.
AB  - Constitutive Stat5 activation enhanced cell survival and resistance to imatinib
      (IM) in chronic myelogenous leukemia (CML) cells. However, the mechanism of Stat5
      activation in mediating resistance to IM in bone marrow (BM) microenvironment has
      not been evaluated precisely. In this study, we reported HS-5-derived conditioned
      medium (CM) significantly enhanced IM resistance in K562 and KU812.
      Interestingly, upregulation of the proportion of CD34+ subpopulation was found in
      CML cells. Subsequently, the BCR/ABL-independent activation of Stat5 increased P
      glycoprotein (P-gp) activity in CM-mediated protection of CML stem cells (LSCs)
      from IM. Further research revealed Stat5 activation increased the DNA binding
      activity of NF-kappaB though binding of p-Stat5 and p-RelA in nucleus. Moreover,
      highly acetylated RelA was required for Stat5-mediated RelA nuclear binding. The
      study further confirmed that Wogonin potentiated the inhibitory effects of IM on
      leukemia development by suppressing Stat5 pathway both in CM model and the K562
      xenograft model. In summary, results clearly demonstrated BCR/ABL-independent
      Stat5 survival pathway could contribute to resistance of CML LSCs to IM in BM
      microenvironment and suggested that natural durgs effectively inhibiting Stat5
      may be an attractive approach to overcome resistance to BCR/ABL kinase
      inhibitors. 

PMID- 27027439
TI  - A novel scoring system predicts adjuvant chemolipiodolization benefit for
      hepatocellular carcinoma patients after hepatectomy.
AB  - Our aim in this study was to develop a prognostic scoring system with which to
      identify patients most likely to benefit from adjuvant chemolipiodolization (ACL)
      after liver resection for hepatocellular carcinoma (HCC). Data from 1150 HCC
      patients who underwent liver resection between 2002 and 2008 at the Eastern
      Hepatobiliary Surgery Hospital were used to develop the scoring system. Patients
      were stratified into prognostic subgroups using the new scoring system, and the
      outcomes of patients who received ACL and those who did not were compared in each
      subgroup. Using data from 379 patients operated on between 2008 and 2010 for
      validation, the scoring system had a concordance index (C-index) of 0.75 for
      predicting post-resectional overall survival (OS). It optimally stratified
      patients into three prognostic subgroups with scores of 0-5, 6-9 and >= 10,
      having better, medium and worse survival outcomes, respectively. A difference in
      OS between ACL and non-ACL patients was only detected in the subgroup with scores
      >= 10 (1-, 3-, and 5-year OS rates: 63.9%, 22.6%, and 9.0% vs. 33.8%, 5.6%, and
      2.8%, p = 0.001). Our proposed scoring system provides an effective tool for
      selecting the patients most likely to benefit from ACL. 

PMID- 27027440
TI  - Preoperative platelet to lymphocyte ratio is a valuable prognostic biomarker in
      patients with colorectal cancer.
AB  - OBJECTIVES: Recent studies suggest that an elevated preoperative platelet to
      lymphocyte ratio (PLR) may be considered a poor prognostic biomarker in patients
      with colorectal cancer (CRC). The aim of this study was to evaluate the
      prognostic impact of PLR in patients with CRC. METHODS: We enrolled 1314 patients
      who underwent surgery for CRC between 2005 and 2011. Preoperative PLR level was
      stratified into quintiles for Kaplan-Meier analysis and multivariable Cox
      proportional hazard regression models. RESULTS: Higher PLR quintiles were
      significantly associated with poorer overall survival (P = 0.002). Multivariate
      analysis showed that PLR was an independent risk factor for overall survival (OS)
      (P = 0.034). Patients in PLR quintile 5 had lower overall survival than in
      quintile 1 (hazard ratio (HR) = 1.701, 95% confidence interval (CI): 1.267-2.282,
      P < 0.001). Although patients in PLR quintile 5 had significantly lower disease
      free survival (DFS) than in quintile 1 (HR = 1.522, 95% CI: 1.114-2.080, P =
      0.008), this association was not significant after multivariable adjustment (P =
      0.075). In the subgroup analysis, PLR remained an independent factor in terms of
      advanced tumor stage (III, IV), male sex, carcinoembryonic antigen (<= 5 ng/ml),
      age (> 65 years) and body mass index (<= 25) (P < 0.05 for all measurements). The
      results remained unchanged when the PLR was analyzed as a dichotomous variable by
      applying different cut-off values of 150, 185, 220. CONCLUSIONS: Elevated
      preoperative PLR was independently associated with an increased risk of mortality
      in patients with CRC. The utility of PLR may help to improve prognostic
      predictors.

PMID- 27027441
TI  - Small flexible structure for targeted delivery of therapeutic and imaging
      moieties in precision medicine.
AB  - The goals of precision medicine are to link diagnostic and therapeutic agents,
      improve clinical outcomes, and minimize side effects. We present a simple, small,
      flexible three-armed core structure that can be conjugated to targeting, imaging,
      and therapeutic moieties. The targeting molecule can be a peptide, protein, or
      chemical compound. The diagnostic reporter can be optical and/or nuclear in
      nature, and can be replaced by chemo- and/or radiotherapeutic compounds for
      treatment using a single targeting molecule. Imaging components can be used to
      detect disease biomarkers, monitor treatment response, and guide surgery in real
      time to create a tumor-free margin. Isotope impurity can be exploited to
      visualize whole-body distribution of therapeutic agents. The one-to-one ratio of
      targeting component to therapeutic agents facilitates dose calculation. The
      simple synthesis and flexible, modular nature of the agent facilitate high
      purity, large-scale production. The core capacity to "seek, treat, and see" may
      advance precision medicine in the future. 

PMID- 27027442
TI  - IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis
      in the small and large intestine.
AB  - Although IL-10 promotes a regulatory phenotype of CD11c+ dendritic cells and
      macrophages in vitro, the role of IL-10 signaling in CD11c+ cells to maintain
      intestinal tolerance in vivo remains elusive. To this aim, we generated mice with
      a CD11c-specific deletion of the IL-10 receptor alpha (Cd11ccreIl10rafl/fl). In
      contrast to the colon, the small intestine of Cd11ccreIl10rafl/fl mice exhibited
      spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes
      and lamina propria T cells, associated with elevated levels of T cell-derived
      IFNgamma and IL-17A. Whereas naive mucosal T-cell priming was not affected and
      oral tolerance to ovalbumin was intact, augmented T-cell function in the lamina
      propria was associated with elevated numbers of locally dividing T cells,
      expression of T-cell attracting chemokines and reduced T-cell apoptosis. Upon
      stimulation, intestinal IL-10Ralpha deficient CD11c+ cells exhibited increased
      activation associated with enhanced IL-6 and TNFalpha production. Following
      colonization with Helicobacter hepaticus Cd11ccreIl10rafl/fl mice developed
      severe large intestinal inflammation characterized by infiltrating T cells and
      increased levels of Il17a, Ifng, and Il12p40. Altogether these findings
      demonstrate a critical role of IL-10 signaling in CD11c+ cells to control small
      intestinal immune homeostasis by limiting reactivation of local memory T cells
      and to protect against Helicobacter hepaticus-induced colitis. 

PMID- 27027443
TI  - FOXO4 and FOXD3 are predictive of prognosis in gastric carcinoma patients.
AB  - Forkhead box (FOX) transcription factor family plays an important role in cancer
      growth and metastasis. This study aimed to determine the predictive ability of
      FOX genes in gastric carcinoma. A total of 360 patients with gastric from The
      Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression
      profile of FOX family were obtained from the TCGA RNAseq database.
      Clinicopathological characteristics, including age, gender, tumor node metastasis
      (TNM), tumor grade, and overall survival were collected. Univariate and
      multivariate Cox proportional hazards model were used to assess the risk factors
      for survival, and the results were further validated in in-house cohort. In the
      TCGA cohort, FOXO4 (HR = 0.613, 95%CI 0.452-0.832) and FOXD3 (HR = 1.704, 95%CI
      1.212-2.397) were shown independently predictive of overall survival in gastric
      cancer after Cox proportional hazards analysis. The finding was validated in our
      in-house cohort, which demonstrated that both FOXO4 and FOXD3 were independent
      predictors for overall survival (FOXO4 high, HR: 0.445, 95%CI 0.277-0.715, P =
      0.001, FOXD3 high, HR: 1.927, 95%CI 1.212-3.063, P = 0.006) and disease free
      survival (FOXO4 high, HR: 0.628, 95%CI 0.420-0.935, P = 0.022, FOXD3 high, HR:
      1.698, 95%CI 1.136-2.540, P = 0.010).Collectively, FOX family paly critical roles
      in gastric cancer, and FOXO4 and FOXD3 were identified as independent prognostic
      factors for survival outcomes of gastric cancer. Further functional study is
      needed to understand more about FOX family in gastric cancer. 

PMID- 27027444
TI  - Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic
      factor for survival in breast cancer patient.
AB  - BRCA1 promoter methylation is an essential epigenetic transcriptional silencing
      mechanism, related to breast cancer (BC) occurrence and progression. We
      quantified the methylation level of BRCA1 promoter and evaluated its significance
      as prognostic and predictive factor. BRCA1 promoter methylation level was
      quantified by pyrosequencing in surgical cancerous and adjacent normal specimens
      from 154 BC patients. A follow up of 98 months was conducted to assess the
      correlation between BRCA1-methylation level vs. overall survival (OS) and disease
      free survival (DFS). The mean methylation level in BC tissues was significantly
      higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%;
      median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R =
      0.7328, P < 0.0001) were significantly correlated with the methylation level.
      Patients with unmethylated BRCA1 had a better OS and DFS compared to the
      methylated group (each P < 0.0001). BRCA1 promoter methylation level has a
      statistically significance on survival in BC patients (HazR = 1.465, P = 0.000)
      and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P =
      0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2
      tumors had a better OS and DFS. Classification of grades and molecular subtypes
      did not show any prognostic significance. Pyrosequencing is a precise and
      efficient method to quantify BRCA1 promoter methylation level, with a high
      potential for future clinical implication, as it identifies subgroups of patients
      with poorer prognosis. 

PMID- 27027446
TI  - A double-negative feedback loop between E2F3b and miR- 200b regulates docetaxel
      chemosensitivity of human lung adenocarcinoma cells.
AB  - MicroRNAs (miRNAs) are non-coding small RNAs which negatively regulate gene
      expressions mainly through 3'-untranslated region (3'-UTR) binding of target
      mRNAs. Recent studies have highlighted the feedback loops between miRNAs and
      their target genes in physiological and pathological processes including
      chemoresistance of cancers. Our previous study identified miR-200b/E2F3 axis as a
      chemosensitivity restorer of human lung adenocarcinoma (LAD) cells. Moreover,
      E2F3b was bioinformatically proved to be a potential transcriptional regulator of
      pre-miR-200b gene promoter. The existance of this double-negative feedback
      minicircuitry comprising E2F3b and miR-200b was confirmed by chromatin
      immunoprecipitation (ChIP) assay, site-specific mutation and luciferase reporter
      assay. And the underlying regulatory mechanisms of this feedback loop on
      docetaxel resistance of LAD cells were further investigated by applying in vitro
      chemosensitivity assay, colony formation assay, flow cytometric analysis of cell
      cycle and apoptosis, as well as mice xenograft model. In conclusion, our results
      suggest that the double-negative feedback loop between E2F3b and miR-200b
      regulates docetaxel chemosensitivity of human LAD cells mainly through cell
      proliferation, cell cycle distribution and apoptosis. 

PMID- 27027445
TI  - Small-molecule inhibition of STAT3 in radioresistant head and neck squamous cell
      carcinoma.
AB  - While STAT3 has been validated as a target for treatment of many cancers,
      including head and neck squamous cell carcinoma (HNSCC), a STAT3 inhibitor is yet
      to enter the clinic. We used the scaffold of C188, a small-molecule STAT3
      inhibitor previously identified by us, in a hit-to-lead program to identify C188
      9. C188-9 binds to STAT3 with high affinity and represents a substantial
      improvement over C188 in its ability to inhibit STAT3 binding to its pY-peptide
      ligand, to inhibit cytokine-stimulated pSTAT3, to reduce constitutive pSTAT3
      activity in multiple HNSCC cell lines, and to inhibit anchorage dependent and
      independent growth of these cells. In addition, treatment of nude mice bearing
      xenografts of UM-SCC-17B, a radioresistant HNSCC line, with C188-9, but not C188,
      prevented tumor xenograft growth. C188-9 treatment modulated many STAT3-regulated
      genes involved in oncogenesis and radioresistance, as well as radioresistance
      genes regulated by STAT1, due to its potent activity against STAT1, in addition
      to STAT3. C188-9 was well tolerated in mice, showed good oral bioavailability,
      and was concentrated in tumors. Thus, C188-9, either alone or in combination with
      radiotherapy, has potential for use in treating HNSCC tumors that demonstrate
      increased STAT3 and/or STAT1 activation. 

PMID- 27027447
TI  - Improving molecular diagnosis of Chinese patients with Charcot-Marie-Tooth by
      targeted next-generation sequencing and functional analysis.
AB  - Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral
      neuropathy. More than 50 causative genes have been identified. The lack of
      genotype-phenotype correlations in many CMT patients make it difficult to decide
      which genes are affected. Recently, targeted next-generation sequencing (NGS) has
      been introduced as an alternative approach for diagnosis of genetic disorders.
      Here, we applied targeted NGS in combination with PMP22 duplication/deletion
      analysis to screen causative genes in 22 Chinese CMT families. The novel variants
      detected by targeted NGS were then further studied in cultured cells. Of the 22
      unrelated patients, 8 had PMP22 duplication. The targeted NGS revealed 10
      possible pathogenic variants in 11 patients, including 7 previously reported
      variants and 3 novel heterozygous variants (GJB1: p.Y157H; MFN2: p.G127S; YARS:
      p.V293M). Further classification of the novel variants according to American
      College of Medical Genetics and Genomics (ACMG) standards and guidelines and
      functional analysis in cultured cells indicated that p.Y157H in GJB1 was
      pathogenic, p.G127S in MFN2 was likely pathogenic, while p.V293M in YARS was
      likely benign. Our results suggest the potential for targeted NGS to make a more
      rapid and precise diagnosis in CMT patients. Moreover, the functional analysis is
      required when the novel variants are indistinct. 

PMID- 27027448
TI  - PI3K/Akt promotes feedforward mTORC2 activation through IKKalpha.
AB  - The ser-thr Akt plays a critical role in the regulation of cell survival, cell
      growth and proliferation, as well as energy metabolism and is dysregulated in
      many cancers. The regulation of Akt activity depends on the phosphorylation at
      two sites: (i) Thr308 in the activation loop by phosphoinositide-dependent kinase
      1 (PDK1) and (ii) Ser473 hydrophobic motif at the carboxyl terminus by a second
      activity termed PDK2, which is the mTORC2 complex composed of mTOR, rictor, and
      Sin1. Previously we demonstrated that IKKalpha, a component of the IKK complex
      that controls NF-kappaB activation, participates in the Akt-dependent regulation
      of mTORC1. Here we have explored a potential involvement of IKKalpha in
      controlling Akt activity and whether this may involve mTORC2. The experiments
      show that IKKalpha associates with mTORC2 in several cancer cells in a manner
      dependent on PI3K/Akt activity and that IKKalpha positively promotes Akt
      phosphorylation at Ser473 and at Thr308. Moreover, IKKalpha enhances mTORC2
      kinase activity directed to Akt on Ser473 and Akt-mediated phosphorylation of
      FOXO3a and GSK3beta, but not other Akt-associated targets such as TSC2 and
      PRAS40, indicating the existence of multiple mechanisms of Akt activation in
      cells. In addition, loss of IKKalpha suppresses growth factor-induced Akt
      activation associated with mTORC1 inhibition. These results indicate that
      IKKalpha serves as a feedforward regulator of mTORC2 and that IKKalpha could
      serve as a key therapeutic target to block mTORC2 and Akt activation in some
      cancers. 

PMID- 27027449
TI  - Efficacy of Neutral Electrolyzed Water, Quaternary Ammonium and Lactic Acid-Based
      Solutions in Controlling Microbial Contamination of Food Cutting Boards Using a
      Manual Spraying Technique.
AB  - Bactericidal activity of neutral electrolyzed water (NEW), quaternary ammonium
      (QUAT), and lactic acid-based solutions was investigated using a manual spraying
      technique against Salmonella Typhimurium, Escherichia coli O157:H7, Campylobacter
      jejuni, Listeria monocytogenes and Staphylococcus aureus that were inoculated
      onto the surface of scarred polypropylene and wooden food cutting boards.
      Antimicrobial activity was also examined when using cutting boards in preparation
      of raw chopped beef, chicken tenders or salmon fillets. Viable counts of
      survivors were determined as log10 CFU/100 cm(2) within 0 (untreated control), 1,
      3, and 5 min of treatment at ambient temperature. Within the first minute of
      treatment, NEW and QUAT solutions caused more than 3 log10 bacterial reductions
      on polypropylene surfaces whereas less than 3 log10 reductions were achieved on
      wooden surfaces. After 5 min of treatment, more than 5 log10 reductions were
      achieved for all bacterial strains inoculated onto polypropylene surfaces. Using
      NEW and QUAT solutions within 5 min reduced Gram-negative bacteria by 4.58 to
      4.85 log10 compared to more than 5 log10 reductions in Gram-positive bacteria
      inoculated onto wooden surfaces. Lactic acid treatment was significantly less
      effective (P < 0.05) compared to NEW and QUAT treatments. A decline in
      antimicrobial effectiveness was observed (0.5 to <2 log10 reductions were
      achieved within the first minute) when both cutting board types were used to
      prepare raw chopped beef, chicken tenders or salmon fillets. 

PMID- 27027450
TI  - [Proposal of a model for the evaluation of public oral health care for children].
AB  - This article proposes a model for quality evaluation of oral health care in
      children. The conceptual framework for the evaluation matrix consisted of
      evaluation studies on oral health care services in Brazil and other countries and
      a survey and review of prevailing public policies for children's health in
      Brazil. Two dimensions, Management and Provision, were evaluated in the quality
      of municipal management of pediatric oral health care. Management included two
      component dimensions, articulation and resources, while Provision included two
      more, "promotion and prevention" and "diagnosis and treatment". The evaluation
      matrix consisted of nine indicators in the Management dimension and nine in the
      Provision dimension. The indicators were elaborated in workshops with
      specialists. The model proved appropriate for application in municipalities with
      different population sizes and allows identifying the areas where managers should
      improve their actions. 

PMID- 27027451
TI  - [Democratic management and institutional support in primary care in the Federal
      District, Brazil].
AB  - The study was performed within the framework of the Brazilian Unified National
      Health System (SUS) in the Federal District, Brazil, focusing on the role of
      institutional support in reframing work and management practices in primary care.
      The study aimed to map practices for supporting primary care in the Recanto das
      Emas Regional Administration, correlated with the Federal District's health
      priorities. The study design included qualitative intervention research with
      participant methods and production of collective narratives. Testing the support
      provided qualification and alignment of institutional measures with management
      priorities, qualification, humanization, and improvement of work and management
      processes, collegiate decision-making, and intervention in daily practices in
      primary care services. The study concludes that support practices can enhance
      democratic management processes and contribute to improving care. 

PMID- 27027452
TI  - [Association between the degree of implementation of the Brazilian Breastfeeding
      Network and breastfeeding indicators].
AB  - This study aimed to evaluate the implementation of the Brazilian Breastfeeding
      Network and its impact on breastfeeding indicators. Implementation was analyzed
      according to type, including 56 primary healthcare units from three Brazilian
      municipalities. For evaluation of the degree of implementation, a score was
      created for each unit based on compliance with Ministry of Health certification
      criteria. Effects of implementation were analyzed according to exclusive and
      overall breastfeeding rates. Eighteen (32.1%) of the units met the four criteria
      for certification. The study sample included 1,052 children less than one year of
      age, of whom 563 were less than six months old. Units that met the four criteria
      for certification showed higher rates of exclusive breastfeeding (44%) when
      compared to the other units. Difficulties in implementing the Brazilian
      Breastfeeding Network were identified, and breastfeeding indicators varied
      according to the number of certification criteria met by the primary healthcare
      unit. 

PMID- 27027453
TI  - [Religious representations in illness experience: a case study].
AB  - This article, the byproduct of a larger research project, presents a case study
      of a Jehovah's Witness with hypertension and cardiac problems. Semi-structured
      interviews were used to reconstruct the individual's illness experience:
      diagnosis, treatments, and cure, focusing on pervasive religious social
      representations, lending meaning to his own life and to the physical and moral
      suffering and disturbances involved in this process. 

PMID- 27027454
TI  - [Inequities in access to food stamps and meal vouchers in Brazil: an analysis of
      the Brazilian Household Budgets Survey, 2008-2009].
AB  - Food stamps and meal vouchers can determine workers' dietary choices. The study
      aimed to assess the coverage of these benefits in Brazil and their distribution
      according to the beneficiaries' socio-demographic and regional characteristics,
      using data from the Brazilian Household Budgets Survey, 2008-2009. Eligibility
      criteria were having an occupation and a private or government job, including
      domestic or temporary work in rural areas. Only 3.2% of eligible individuals
      reported receiving such benefits. Highest coverage rates were verified with the
      Southeast region, urban areas, male gender, employment in the private sector, and
      monthly earnings > five times the minimum wage. The mean monthly amount of such
      benefits was R$ 177.20 (US$ 100 at the 2009 exchange rate). After adjusting for
      other variables, the highest amounts were associated with male gender, higher
      salaries, the Northeast and Central regions, and employment in the public sector.
      This first analysis of the national coverage of food stamps and meal vouchers
      showed that a large share of Brazilian workers lack access or have unequal access
      to such benefits. 

PMID- 27027455
TI  - [Prevalence of home care and associated factors in the Brazilian elderly
      population].
AB  - The aim of this study was to evaluate the prevalence of home care for the
      Brazilian elderly population and associated factors, using a cross-sectional
      design with a sample of individuals 60 years or older living in the urban areas
      of 100 municipalities located in 23 states. A Poisson regression model was used
      for crude and adjusted analyses. A total of 6,624 elderly individuals were
      interviewed, and prevalence of home care was 11.7%. After adjustment, higher home
      care rates were associated with female gender, older old age, lower schooling and
      purchasing power, diagnosis of chronic illness, history of falls, previous
      hospitalization, and medical consultation in the previous three months. The
      results highlight more extensive use of home care by the most vulnerable elderly.
      This finding suggests a contribution from home care to the promotion of
      healthcare equity in Brazil, especially due to the expansion of the Family Health
      Strategy. The results can support the organization of the work process for
      primary care professionals and managers. 

PMID- 27027456
TI  - Regulation of the synthetic estrogen 17alpha-ethinylestradiol in water bodies in
      Europe, the United States, and Brazil.
AB  - The synthetic estrogen 17alpha-ethinylestradiol, the principal component of oral
      contraceptives, has been identified as one of the main compounds accounting for
      adverse effects on the endocrine system in various species. This study aimed to
      analyze the state-of-the-art in legislation and guidelines for the control of
      this synthetic estrogen in water bodies in Europe and the United States and to
      draw a parallel with the Brazilian reality. Countries have generally attempted to
      expand the regulation and monitoring of certain emerging micropollutants not
      previously covered by legislation. Europe is more advanced in terms of water
      quality, while in the United States this estrogen is only regulated in water for
      human consumption. Brazil still lacks legal provisions or standards for this
      estrogen, which can be explained by the relatively limited maturity of the
      country's system for controlling water pollutants. 

PMID- 27027457
TI  - [Hospitalizations for ambulatory care-sensitive conditions: validation study at a
      Hospital Information System (SIH) in the Federal District, Brazil, in 2012].
AB  - This study analyzes hospitalizations due to ambulatory care-sensitive conditions
      with a focus on infectious and parasitic diseases (IPDs) and validates the
      Hospital Information System, Brazilian Unified National Health System (SIH/SUS)
      for recording hospitalizations due to ambulatory care-sensitive conditions in a
      hospital in the Federal District, Brazil, in 2012. The study estimates the
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of the SIH for recording hospitalizations due to
      ambulatory care-sensitive conditions, with the patient's medical file as the gold
      standard. There were 1,604 hospitalizations for hospitalizations due to
      ambulatory care-sensitive conditions (19.6%, 95%CI: 18.7-20.5), and the leading
      IPDs were renal and urinary tract infection, infection of the skin and
      subcutaneous tissue, and infectious gastroenteritis. IPDs were the leading cause
      of hospitalization in the 20 to 29-year age bracket and caused 28 deaths.
      Sensitivity was 70.1% (95%CI: 60.5-79.7), specificity 88.4% (95%CI: 85.6-91.2),
      PPV = 51.7% (95%CI: 42.7-60.7), and NPV = 94.3% (95%CI: 92.2-96.4). The findings
      for admissions due to ACSCs in this hospital were similar to those of other
      studies, featuring admissions for IPDs. The SIH/SUS database was more specific
      than sensitive. 

PMID- 27027458
TI  - [Managing comprehensive care: a case study in a health district in Bahia State,
      Brazil].
AB  - This study analyzed management of comprehensive care in a health district in
      Bahia State, Brazil, at the political, institutional, organizational, and
      healthcare practice levels and the challenges for establishing coordinated care
      between municipalities. The information sources were semi-structured interviews
      with administrators, focal groups with healthcare professionals and users,
      institutional documents, and observations. A comprehensive and critical analysis
      was produced with dialectical hermeneutics as the reference. The results show
      that the Inter-Administrators Regional Commission was the main regional
      governance strategy. There is a fragmentation between various points and lack of
      communications linkage in the network. Private interests and partisan political
      interference overlook the formally agreed-upon flows and create parallel
      circuits, turning the right to health into currency for trading favors. Such
      issues hinder coordination of comprehensive care in the inter-municipal network. 

PMID- 27027459
TI  - [Legislation on primary care in Brazilian Unified National Health System:
      document analysis].
AB  - A reflection on Brazil's legislation for primary care helps understand the way
      health policy is implemented in the country. This study focuses on the legal
      provisions aimed at strengthening primary care, drawing on an analysis of
      documents from the Ministry of Health's priority actions, programs, and
      strategies. A total of 224 provisions were identified, in two groups of
      documents, so-called instituting provisions and complementary provisions. The
      former include the principles and guidelines of the Brazilian Unified National
      Health System (SUS) and also involve the expansion of actions. Financing was a
      quantitatively central theme, especially in the complementary provisions. The
      analysis led to reflection on the extent to which these strategies can induce
      linkage between health system managers and civil society in building a political
      project resulting in improvements and meeting the population's health needs. 

PMID- 27027460
TI  - One and a half degrees. So what?

PMID- 27027461
TI  - A comprehensive assessment of cardiovascular autonomic control using
      photoplethysmograms recorded from the earlobe and fingers.
AB  - We compare the spectral indices of photoplethysmogram variability (PPGV)
      estimated using photoplethysmograms recorded from the earlobe and the middle
      fingers of the right and left hand and analyze their correlation with similar
      indices of heart rate variability (HRV) in 30 healthy subjects (26 men) aged 27
      (25, 29) years (median with inter-quartile ranges) at rest and under the head-up
      tilt test. The following spectral indices of PPGV and HRV were compared: mean
      heart rate (HR), total spectral power (TP), high-frequency (HF) and low-frequency
      (LF) ranges of TP in percents (HF% and LF%), LF/HF ratio, and spectral coherence.
      We assess also the index S of synchronization between the LF oscillations in HRV
      and PPGV. The constancy of blood pressure (BP) and moderate increase of HR under
      the tilt test indicate the presence of fast processes of cardiovascular
      adaptation with the increase of the sympathetic activity in studied healthy
      subjects. The impact of respiration on the PPGV spectrum (accessed by HF%) is
      less than on the HRV spectrum. It is shown that the proportion of sympathetic
      vascular activity (accessed by LF%) is constant in the PPGV of three analyzed
      PPGs during the tilt test. The PPGV for the ear PPG was less vulnerable to
      breathing influence accessed by HF% (independently from body position) than for
      PPGs from fingers. We reveal the increase of index S under the tilt test
      indicating the activation of interaction between the heart and distal vessels.
      The PPGV spectra for finger PPGs from different hands are highly coherent, but
      differ substantially from the PPGV spectrum for the ear PPG. We conclude that
      joint analysis of frequency components of PPGV (for the earlobe and finger PPGs
      of both hands) and HRV and assessment of their synchronization provide additional
      information about cardiovascular autonomic control. 

PMID- 27027462
TI  - Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of
      KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation.
AB  - BACKGROUND: Single-nucleotide polymorphisms in genes involved in pain control
      might predispose to exaggerated sensitivity or difference in opioid analgesic
      effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the
      catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, ValMet) single
      nucleotide polymorphisms were studied in preterm infants needing intubation and
      randomized to a premedication strategy including remifentanil (n = 17) or
      morphine (n = 17). METHODS: Pain was scored with Astrid Lindgren and Lund
      Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain
      relief provided by the opioids was compared between the different KCNJ6 and COMT
      genotypes. RESULTS: Infants homozygous for the KCNJ6 -1250A allele had an
      increased duration after intubation to achieve a score indicating no pain
      compared with infants with the A/G or G/G genotypes (182 +/- 30, 109 +/- 29, and
      60 +/- 21 minutes, respectively; Logrank = 7.5, P = 0.006). Similarly, the
      duration was increased in individuals with the COMT Val/Val alleles compared with
      Val/Met and Met/Met (285 +/- 37, 137 +/- 25, and 63 +/- 15 minutes, respectively;
      Logrank = 14.4, P = 0.0021). Cox proportional hazards analysis confirmed that the
      variation in both genes was independently associated with susceptibility to
      respond to therapy. CONCLUSION: We conclude that the KCNJ6 -1250A and COMT Val
      alleles are predisposing preterm newborns to diminished opioid-induced pain
      relief.

PMID- 27027463
TI  - A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying
      Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer
      to a Fully Breast-Fed Neonate.
AB  - BACKGROUND: Amisulpride is a second generation atypical antipsychotic drug. The
      management of psychosis exacerbation in late pregnancy or during lactation is
      often hampered by inadequate knowledge of risk to the baby from placental
      transfer or breast milk transfer of drugs. There is no specific information on
      adverse effects from amisulpride. To gather guiding information from one mother
      baby pair, we conducted a drug concentration study on the fourth post-natal day
      and developed a novel liquid chromatography-tandem mass spectrometry method with
      application to the very small plasma volumes obtainable from a neonate, requiring
      15 MUL of plasma, and with application to human breast milk. METHODS: Plasma and
      breast milk extracts, spiked with deuterated internal standard (amisulpride-d5)
      were separated isocratically with a buffered water-methanol-acetonitrile mobile
      phase. A tandem mass spectrometer in positive electrospray ionisation mode with
      multiple reaction monitoring was used for detection. RESULTS: Method linearity,
      sensitivity, imprecision, matrix effects, recovery, and overall process
      efficiency were satisfactory for milk and plasma. No interferences were found
      from a broad range of psychotropic and general drugs. The breast milk area under
      the concentration-time curve for the interval 0-12 hours was 10,726 mcg.h.L,
      corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk
      amisulpride was 12-fold higher than the simultaneous plasma concentration. The
      baby's plasma amisulpride concentration was 10.5% of the maternal plasma
      concentration. CONCLUSIONS: An assay was developed that is suitable for
      therapeutic drug monitoring of amisulpride. Its application to breast milk and
      neonate plasma showed that amisulpride partitioned strongly into breast milk and
      that the neonate reached plasma levels that were more than desirable for a
      psychotropic drug.

PMID- 27027464
TI  - Recent advances in supported employment for people with serious mental illness.
AB  - PURPOSE OF REVIEW: Supported employment is a vocational rehabilitation approach
      that eschews prevocational training in favor of rapid job search for competitive
      work and follow-along supports to sustain employment, with the individual
      placement and support (IPS) model being the most standardized and researched
      model. This review covers recent research on the IPS model of supported
      employment. RECENT FINDINGS: The evidence base for IPS-supported employment
      continues to grow, with seven new randomized controlled trials published, most
      conducted abroad, resulting in a total of 23 controlled studies showing that IPS
      is effective at improving work outcomes. Several reviews have concluded that
      competitive work improves quality of life in persons with serious mental illness,
      and some research has suggested that employment may confer clinical benefits.
      Encouraging research has been published on modifications of the IPS model (such
      as inclusion of supported education), augmentations (such as cognitive
      remediation) and adaptations for underserved populations (such as persons with
      criminal justice involvement). Recent studies have also described the effective
      strategies for implementing and sustaining IPS; others have reported its cost
      effectiveness. SUMMARY: Research continues to accumulate on the effectiveness of
      IPS-supported employment, adaptations of the model and overcoming programme and
      policy barriers to its widespread implementation.

PMID- 27027466
TI  - Using technology to improve access to specialist care in amyotrophic lateral
      sclerosis: A systematic review.
AB  - Our objective was to review the evidence for using technology to improve access
      to specialist care for patients with amyotrophic lateral sclerosis (ALS) and
      their carers. Medline, Google Scholar and the Cochrane library were searched for
      articles describing technology that enabled clinical care of patients with ALS or
      their carers where the patient/carer and clinician were not in the same location.
      Two applications were identified: telemedicine to facilitate video conferencing
      as an alternative to outpatient consultations and telehealth monitoring for
      patients with respiratory failure. One randomized controlled trial using
      telehealth in patients with respiratory failure including 22 patients with ALS
      was identified. While rates of hospitalization were reduced, overall mortality
      was unchanged and there were too few patients with ALS in the study to detect
      significant benefit. In conclusion, there is limited evidence to support the use
      of telemedicine or telehealth in the care of patients with ALS. Future research
      needs to develop an understanding of the key beneficial aspects of the
      traditional specialist ALS service and how these factors could be delivered using
      technology. Successful evaluation and implementation of technologies to
      facilitate access to specialist care will only be possible if all the relevant
      impacts of an intervention are understood and measured.

PMID- 27027467
TI  - Expression ratio of histone demethylase KDM3A to protamine-1 mRNA is predictive
      of successful testicular sperm extraction in men with obstructive and non
      obstructive azoospermia.
AB  - To evaluate the predictive value of histone demethylase KDM3A to protamine 1
      (PRM1) mRNA expression ratio as a reliable marker of sperm retrieval in men with
      obstructive and non-obstructive azoospermia (NOA). Fifty eight azoospermic men,
      including 44 with NOA and 14 with obstructive azoospermia (OA). Testis tissue
      samples were collected from azoospermic men who have been referred for testicular
      sperm extraction (TESE) and micro-TESE. Relative expression ratio of KDM3A to
      PRM1 was analyzed after selection of approved reference genes. Histological
      classification of testis biopsies was performed. Sperm retrieval following TESE
      and micro-TESE was evaluated. A sperm retrieval prediction sensitivity of 95% was
      established when the Cq of PRM1 became smaller than the Cq of both KDM3A and
      GAPDH genes. However, azoospermic men with down-regulated KDM3A and decreased
      expression of PRM1 mRNA showed very low success for sperm retrieval (<25%), even
      after micro-TESE surgery. The KDM3A to PRM1 mRNA expression ratio can be used as
      a reliable marker of successful testicular sperm extraction in men with
      obstructive and non-obstructive azoospermia with 95% sensitivity.

PMID- 27027468
TI  - A capillary electrophoresis system with dual capacitively coupled contactless
      conductivity detection and electrospray ionization tandem mass spectrometry.
AB  - A commercial system that is comprised of a CE coupled to an ESI triple quadrupole
      mass spectrometer was equipped with two capacitively coupled contactless
      conductivity detectors (C(4) Ds). The first C(4) D was positioned inside the
      original cartridge, and the second C(4) D was positioned as close as possible to
      the ESI probe entrance by using a 3D-printed support. The C(4) Ds
      electropherograms were matched to the ESI-MS electropherogram by correcting their
      timescales by the factor LT /LD , where LT and LD are the total capillary length
      and the length until the C(4) D, respectively. A general approach for method
      development supporting the simultaneous conductivity and MS detection is
      discussed, while application examples are introduced. These examples include the
      use of C(4) D as a simple device that dismiss the use of an EOF marker, a low
      selectivity detector that continuously provide information about unexpected
      features of the sample, and even a detector that can be more sensitive than ESI
      MS. The C(4) D used in this setup proved to have a smaller contribution to the
      peak broadening than ESI-MS, which allowed that a C(4) D, positioned at 12 cm
      from the inlet of an 80-cm-long capillary, could be used to foresee position and
      shape of the peaks being formed 6.8 times slower at the ESI-MS electropherogram.

PMID- 27027469
TI  - Smoking and caffeine consumption: a genetic analysis of their association.
AB  - Smoking and caffeine consumption show a strong positive correlation, but the
      mechanism underlying this association is unclear. Explanations include shared
      genetic/environmental factors or causal effects. This study employed three
      methods to investigate the association between smoking and caffeine. First,
      bivariate genetic models were applied to data of 10 368 twins from the
      Netherlands Twin Register in order to estimate genetic and environmental
      correlations between smoking and caffeine use. Second, from the summary
      statistics of meta-analyses of genome-wide association studies on smoking and
      caffeine, the genetic correlation was calculated by LD-score regression. Third,
      causal effects were tested using Mendelian randomization analysis in 6605
      Netherlands Twin Register participants and 5714 women from the Avon Longitudinal
      Study of Parents and Children. Through twin modelling, a genetic correlation of
      r0.47 and an environmental correlation of r0.30 were estimated between current
      smoking (yes/no) and coffee use (high/low). Between current smoking and total
      caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also
      indicated sizeable genetic correlations between smoking and coffee use (r0.44
      between smoking heaviness and cups of coffee per day, r0.28 between smoking
      initiation and coffee use and r0.25 between smoking persistence and coffee use).
      Consistent with the relatively high genetic correlations and lower environmental
      correlations, Mendelian randomization provided no evidence for causal effects of
      smoking on caffeine or vice versa. Genetic factors thus explain most of the
      association between smoking and caffeine consumption. These findings suggest that
      quitting smoking may be more difficult for heavy caffeine consumers, given their
      genetic susceptibility.

PMID- 27027470
TI  - Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in
      trichloroethylene-sensitized mice.
AB  - Trichloroethylene (TCE) is a major environmental pollutant. An immunological
      response is a newly-recognized mechanism for TCE-induced kidney damage. However,
      the role of the plasma kallikrein-kinin system (KKS) in immune-mediated kidney
      injury has never been examined. This study aimed to explore the role of the key
      components of the KKS, i.e. plasma kallikrein (PK), bradykinin (BK) and its
      receptors B1R and B2R, in TCE-induced kidney injury. A mouse model of skin
      sensitization was used to explore the mechanism of injury with or without a PK
      inhibitor PKSI. Kidney function was evaluated by measuring blood urea nitrogen
      (BUN) and creatinine (Cr) in conjunction with histopathologic characterization.
      Plasma BK was determined by ELISA; Renal C5b-9 membrane attack complex was
      evaluated by immunohistochemistry. Expression of BK and PK in the kidney was
      detected by immunofluorescence. mRNA and protein levels of B1R and B2R were
      assessed by real-time qPCR and Western blot. As expected, numerous inflammatory
      cell infiltration and tubular epithelial cell vacuolar degeneration were observed
      in TCE-sensitized mice. Moreover, serum BUN and Cr and plasma BK were increased.
      In addition, deposition of BK, PK and C5b-9 were observed and B1R and B2R mRNA
      and proteins levels were up-regulated. Pre-treatment with PKSI, a highly
      selective inhibitor of PK, alleviated TCE-induced renal damage. In addition, PKSI
      attenuated TCE-induced up-regulation of BK, PK and its receptors and C5b-9. These
      results provided the first evidence that activation of the KKS contributed to
      immune-mediated renal injury induced by TCE and also helped to identify the KKS
      as a potential therapeutic target for mitigating chemical sensitization-induced
      renal damage.

PMID- 27027471
TI  - Understanding the Operative Experience of the Practicing Pediatric Surgeon:
      Implications for Training and Maintaining Competency.
AB  - IMPORTANCE: The number of practicing pediatric surgeons has increased rapidly in
      the past 4 decades, without a significant increase in the incidence of rare
      diseases specific to the field. Maintenance of competency in the index procedures
      for these rare diseases is essential to the future of the profession. OBJECTIVE:
      To describe the demographic characteristics and operative experiences of
      practicing pediatric surgeons using Pediatric Surgery Board recertification case
      log data. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review
      of 5 years of pediatric surgery certification renewal applications submitted to
      the Pediatric Surgery Board between 2009 and 2013. A surgeon's location was
      defined by population as urban, large rural, small rural, or isolated. Case log
      data were examined to determine case volume by category and type of procedures.
      Surgeons were categorized according to recertification at 10, 20, or 30 years.
      MAIN OUTCOME AND MEASURE: Number of index cases during the preceding year.
      RESULTS: Of 308 recertifying pediatric surgeons, 249 (80.8%) were men, and 143
      (46.4%) were 46 to 55 years of age. Most of the pediatric surgeons (304 of 308
      [98.7%]) practiced in urban areas (ie, with a population >50 000 people). All
      recertifying applicants were clinically active. An appendectomy was the most
      commonly performed procedure (with a mean [SD] number of 49.3 [35.0] procedures
      per year), nonoperative trauma management came in second (with 20.0 [33.0]
      procedures per year), and inguinal hernia repair for children younger than 6
      months of age came in third (with 14.7 [13.8] procedures per year). In 6 of 10
      "rare" pediatric surgery cases, the mean number of procedures was less than 2. Of
      308 surgeons, 193 (62.7%) had performed a neuroblastoma resection, 170 (55.2%) a
      kidney tumor resection, and 123 (39.9%) an operation to treat biliary atresia or
      choledochal cyst in the preceding year. Laparoscopy was more frequently performed
      in the 10-year recertification group for Nissen fundoplication, appendectomy,
      splenectomy, gastrostomy/jejunostomy, orchidopexy, and cholecystectomy (P < .05)
      but not lung resection (P = .70). It was more frequently used by surgeons
      recertifying in the 10-year group (used in 11 375 of 14 456 procedures [78.7%])
      than by surgeons recertifying in the 20-year (used in 6214 of 8712 procedures
      [71.3%]) or 30-year group (used in 2022 of 3805 procedures [53.1%]). CONCLUSIONS
      AND RELEVANCE: Practicing pediatric surgeons receive limited exposure to index
      cases after training. With regard to maintaining competency in an era in which
      health care outcomes have become increasingly important, these results are
      concerning.

PMID- 27027474
TI  - Design of Virtual Fixtures for Robotic Cholecystectomy.
AB  - BACKGROUND AND OBJECTIVE: With the ongoing developments in robotic surgery, the
      associated adverse events need to be carefully evaluated. Virtual fixtures (VFs),
      a safety design feature against unintended motion during robotic surgery, have
      been proposed, but the methodology for designing VFs remains experimental. In
      this study, we propose a novel methodology for designing VFs for robotic
      cholecystectomy. MATERIALS AND METHODS: Laparoscopic cholecystectomy (LC) was
      performed in 24 patients with cholecystitis. Active working space (AWS), the
      distance between instrument heads (DBIH), motion speed of bilateral hands, and
      instrument heads were calculated and analyzed. RESULTS: DBIH was 14.78 +/- 6.94
      cm. Diameter of right and left AWS was 15.81 +/- 3.69 cm and 15.33 +/- 1.52 cm,
      respectively. DBIH was found to significantly correlate with the surgeon's
      experience. Bilateral AWS was found to be significantly associated with body
      circumference at Murphy's point level. However, no association was observed
      between bilateral AWS and surgeon's experience. CONCLUSIONS: A novel methodology
      to build VFs for designing VFs for robotic cholecystectomy is established.
      Surgeon's experience appears to play an important role in determining the DBIH
      during robotic laparoscopic cholecystectomy, but does not affect bilateral AWS.

PMID- 27027475
TI  - Evaluation of Antimetastatic Effect of lncRNA-ATB siRNA Delivered Using
      Ultrasound-Targeted Microbubble Destruction.
AB  - Hepatocellular carcinoma (HCC) is one of the most common human malignancies
      around the world. The poor prognosis and high recurrence rate of HCC are largely
      the result of the high frequencies of intrahepatic and extrahepatic metastases.
      However, the treatment of metastasis is very limited. Ultrasound-targeted
      microbubble destruction (UTMD) technology has been recognized as a promising
      technology for drug and gene delivery in vivo and in vitro. Long noncoding RNA
      activated by transforming growth factor-beta (TGF-beta; lncRNA-ATB) was recently
      identified, which was upregulated in HCC metastases and associated with poor
      prognosis of HCC patients. In this study, we used microbubbles for UTMD-mediated
      siRNA transfection to silence lncRNA-ATB expression. We found that UTMD-mediated
      siRNA transfection significantly inhibited lncRNA-ATB expression and ZEB1 and
      ZEB2 expression and suppressed cell migration and invasion. We also demonstrated
      that transfecting siRNA against lncRNA-ATB by using UTMD was more efficient than
      that by using lipidosome. UTMD-mediated siRNA transfection against lncRNA-ATB may
      be a promising therapy for HCC metastasis. 

PMID- 27027476
TI  - Thermo-responsive polymer aided spheroid culture in cryogel based platform for
      high throughput drug screening.
AB  - In high throughput cell culture, the paradigm is now shifting from 2D to 3D
      systems. However, in 3D cell culture systems, it is important that the cells form
      spheroids with robust cell-cell interactions. We fabricated poly(N
      isopropylacrylamide-co-gelatin) cryogel scaffolds for cell culture and inserted
      them into open-ended 96-well plates that formed a drainage and leakage protected,
      easy to handle high throughput platform. This platform was used to screen for the
      optimal concentration of poly(N-isopropylacrylamide) (pNIPAAm) as an external aid
      to the formation of cellular spheroids. It was found that hepatic cells (Hep G2)
      seeded in the presence of 0.03% pNIPAAm formed better hepatic spheroids in terms
      of morphology (as assessed by microscopic analysis and formation of bile
      canaliculi-like structures) and functionality by day 5 of culture. An increase of
      44.22%, 15.75%, 36.44%, 32.05% and 27.02% was observed in glucose consumption
      (1.925 mM per day per 10(4) cells), albumin synthesis (164.18 ng per day per
      10(4) cells), CYP1A1 (304.92 pg per min per 10(4) cells), CYP2A6 (441.23 nM per
      min per 10(4) cells) and phase II metabolic activity (386.18 nM per min(-1) per
      10(4) cells), respectively, upon using 0.03% pNIPAAm, as compared to the 3D
      control. The platform was tested with other cells such as breast and lung cancer
      cells and found to be compatible. The cell spheroids were subjected to drug
      toxicity screening in cryogel based open-ended platforms. It was observed that
      the spheroids were more resistant to anticancer drugs, as compared to 2D and 3D
      controls, with approximately 11%-67% increase in the IC50 values of tamoxifen and
      paclitaxel. The platform also showed dose dependent and reproducible responses to
      drugs. 

PMID- 27027477
TI  - Preparing for the future: a review of tools and strategies to support autonomous
      goal setting for children and youth with autism spectrum disorders.
AB  - PURPOSE: Despite recognized benefits, current clinical practice rarely includes
      direct input from children and youth with autism spectrum disorder (ASD) in
      setting rehabilitation goals. This study reviews tools and evidence-based
      strategies to assist with autonomous goal settings for children and youth with
      ASD. METHOD: This study included two components: (1) A scoping review of existing
      tools and strategies to assist with autonomous goal setting in individuals with
      ASD and (2) a chart review of inter-disciplinary service plan goals for children
      and youth with ASD. RESULTS: Eleven data sources, evaluating five different tools
      to assist with autonomous goal setting for children and youth with ASD, were
      found. Three themes emerged from the integration of the scoping review and chart
      review, which are discussed in the paper: (1) generalizability of findings, (2)
      adaptations to support participation and (3) practice implications. CONCLUSIONS:
      Children and youth with ASD can participate in setting rehabilitation goals, but
      few tools to support their participation have been evaluated, and those tools
      that do exist do not align well with current services foci. Visual aids appear to
      be one effective support, but further research on effective strategies for
      meaningful engagement in autonomous goal setting for children and youth with ASD
      is warranted. Implications for rehabilitation Persons with ASD are less self
      determined than their peers. Input into one's own rehabilitation goals and
      priorities is an important component of self-determination. Few tools exist to
      help engage children and youth with ASD in setting their own rehabilitation
      goals. An increased focus on identifying, developing and evaluating effective
      tools and strategies to facilitate engagement of children and youth with ASD in
      setting their own rehabilitation goals is warranted.

PMID- 27027478
TI  - Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel
      Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles.
AB  - The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4
      b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid
      heterocycles have been achieved through the 1,3-dipolar cycloaddition of
      azomethine ylides generated in situ from alpha-amino acids and 1,2-diketones to
      dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

PMID- 27027479
TI  - Are there higher pedestrian fatalities in larger cities?: A scaling analysis of
      115 to 161 largest cities in the United States.
AB  - OBJECTIVE: In 2012, 4,743 pedestrians were killed in the United States,
      representing 14% of total traffic fatalities. The number of pedestrians injured
      was higher at 76,000. Therefore, 36 out of 52 of the largest cities in the United
      States have adopted a citywide target of reducing pedestrian fatalities. The
      number of cities adopting the reduction goal during 2011 and 2012 increased
      rapidly with 8 more cities. We examined the scaling relationship of pedestrian
      fatality counts as a function of the population size of 115 to 161 large U.S.
      cities during the period of 1994 to 2011. We also examined the scaling
      relationship of nonpedestrian and total traffic fatality counts as a function of
      the population size. METHODS: For the data source of fatality measures we used
      Traffic Safety Facts Fatality Analysis Reporting System/General Estimates System
      annual reports published each year from 1994 to 2011 by the NHTSA. Using the data
      source we conducted both annual cross-sectional and panel data bivariate and
      multivariate regression models. In the construction of the estimated functional
      relationship between traffic fatality measures and various factors, we used the
      simple power function for urban scaling used by Bettencourt et al. ( 2007 , 2010
      ) and the refined STIRPAT (stochastic impacts by regression on population,
      affluence, and technology) model used in Dietz and Rosa ( 1994 , 1997 ) and York
      et al. ( 2003 ). RESULTS: We found that the scaling relationship display
      diseconomies of scale or sublinear for pedestrian fatalities. However, the
      relationship displays a superlinear relationship in case of nonpedestrian
      fatalities. The scaling relationship for total traffic fatality counts display a
      nearly linear pattern. When the relationship was examined by the 4 subgroups of
      cities with different population sizes, the most pronounced sublinear scaling
      relationships for all 3 types of fatality counts was discovered for the subgroup
      of megacities with a population of more than 1 million. CONCLUSIONS: The scaling
      patterns of traffic fatalities of subgroups of cities depend on population sizes
      of the cities in subgroups. In particular, 9 megacities with populations of more
      than 1 million are significantly different from the remaining cities and should
      be viewed as a totally separate group. Thus, analysis of the patterns of traffic
      fatalities needs to be conducted within the group of megacities separately from
      the other cities with smaller population sizes for devising prevention policies
      to reduce traffic fatalities in both megacities and smaller cities.

PMID- 27027480
TI  - Brief educational strategies for improving contraception use in young people.
AB  - BACKGROUND: Global high rates of unplanned pregnancy and abortion among young
      women demonstrate the need for increased access to modern contraceptive services.
      In sub-Saharan Africa, the birth rate for those aged 15 to 19 years is 121 per
      1000. In the USA, 6% of teens aged 15 to 19 years became pregnant in 2010. Most
      pregnancies among young women to age 25 are unintended. OBJECTIVES: The aim was
      to identify brief educational interventions for improving contraceptive use among
      young people that are feasible for implementing in a clinic or similar setting
      with limited resources. SEARCH METHODS: To 7 March 2016, we searched for studies
      in CENTRAL, PubMed, POPLINE, Web of Science, ClinicalTrials.gov and ICTRP.
      SELECTION CRITERIA: We considered randomized controlled trials (RCTs) that
      assigned individuals or clusters as well as non-randomized studies (NRS). We
      included young people to age 25.The intervention had to be sufficiently brief for
      a clinic, i.e. one to three sessions of 15 to 60 minutes plus potential follow
      up. The strategy had to emphasize one or more effective methods of contraception.
      Primary outcomes were pregnancy and contraceptive use. DATA COLLECTION AND
      ANALYSIS: We assessed titles and abstracts identified during the searches. One
      author extracted and entered the data into Review Manager; a second author
      verified accuracy. We examined studies for methodological quality.For dichotomous
      outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% confidence
      interval (CI). For continuous variables, we computed the mean difference (MD)
      with 95% CI. We used adjusted measures for cluster RCTs, typically ORs, that the
      investigators reported. For NRS, which need to control for confounding, we also
      used reported adjusted measures. We did not conduct meta-analysis due to varied
      interventions and outcome measures. MAIN RESULTS: We found 11 studies, published
      from 1983 to 2015, that included a total of 8338 participants. Ten were from the
      USA and one was from China. We focused here on intervention effects for our
      primary outcomes. Five studies showed some effect on contraceptive use. Of three
      RCTs that examined innovative counseling, one showed an intervention effect. At
      one year, adolescents with developmental counseling were more likely to use
      contraception effectively than those with standard counseling (OR 48.38, 95% CI
      5.96 to 392.63).Three studies used an audiovisual tool plus counseling; two
      reported some effect on contraceptive use. An NRS with young men, aged 15 to 18,
      examined a slide-tape presentation plus reproductive health consultation. At one
      year, the intervention group was more likely than the standard-care group to
      report using an effective contraceptive and having a partner who used oral
      contraceptives (OCs), both at last intercourse (reported adjusted OR 1.51 and
      1.66, respectively). Another study utilized a computer program for contraceptive
      decision-making plus standard counseling for women to age 20. At one year, fewer
      women in the intervention group at one site had not used OCs compared with the
      counseling-only group (3.4% versus 8.8%; reported P = 0.05).Three RCTs provided
      phone follow-up after counseling, one of which showed an effect on contraceptive
      use among women age 16 to 24. Women who received counseling plus phone calls to
      encourage contraceptive use were more likely than the counseling-only group to
      report consistent OC use at three months (OR 1.41, 95% CI 1.06 to 1.87) and six
      months (OR 1.39, 95% CI 1.03 to 1.87). Also at three months, they were more
      likely to report condom use at last sex (OR 1.45, 95% CI 1.03 to 2.03).Two
      cluster randomized trials trained providers on contraceptive methods and
      counseling. One trial with an intervention effect tested comprehensive
      contraceptive services for women to age 25, postabortion. At six months, the
      comprehensive-service group was more likely than the standard-care group to use
      an effective contraceptive (reported adjusted OR 2.03, 95% CI 1.04 to 3.98) and
      to use condoms consistently and correctly (reported adjusted OR 5.68, 95% CI 3.39
      to 9.53). AUTHORS' CONCLUSIONS: Few studies tested brief strategies for young
      people. We noted heterogeneity across studies in participants' ages and life
      situations. Of five studies with some effect, one provided moderate-quality
      evidence; four were older studies with low-quality evidence. More intensive
      strategies could be more effective, but would also be challenging for many
      clinics to implement.

PMID- 27027481
TI  - Development of Reverse Transcription Loop-Mediated Isothermal Amplification for
      Rapid Detection of Batai Virus in Cattle and Mosquitoes.
AB  - Batai virus (BATV) is an arthropod-borne single-stranded RNA virus belonging to
      the genus Orthobunyavirus of the family Bunyaviridae that is primarily
      transmitted by mosquitoes. Methods for detecting BATV are currently limited to
      serological surveillance, virus isolation, and conventional reverse transcription
      polymerase chain reaction (RT-PCR) assay. In this study, we sought to develop a
      BATV detection assay that needs no specialized equipment and is highly specific,
      sensitive, and simple. We first developed and optimized a reverse transcription
      loop-mediated isothermal amplification (RT-LAMP) for rapid detection of BATV that
      uses two pairs of primers to amplify a conserved region of the BATV M gene. The
      optimal reaction conditions for this RT-LAMP BATV detection assay were 40 min at
      65 degrees C. The amplification products could be visualized directly for color
      changes. This RT-LAMP method has a detection limit of 2.86 copies/MUL and a
      sensitivity that was approximately 10- and 100-fold greater than real-time and
      conventional RT-PCR, respectively. RT-LAMP for BATV detection showed no cross
      reactivity with other viruses and its sensitivity was validated with cattle blood
      and mosquito specimens. Our results suggest that this RT-LAMP method was simpler
      and faster than conventional RT-PCR or real-time RT-PCR. Moreover, RT-LAMP
      represents a potential tool to test for BATV in clinical and mosquito samples,
      especially in rural areas of China. This method also shows promise as a
      diagnostic tool due to its rapid and sensitive detection without the need for
      sophisticated equipment or complicated protocols.

PMID- 27027482
TI  - HCV/HTLV coinfection: Does HTLV-1 interfere in the natural history of HCV-related
      diseases?
AB  - Hepatitis C virus (HCV) and human T-lymphotropic virus type 1 (HTLV-1)
      coinfection occurs in many regions. However, few studies have focused on the
      natural history of HCV-induced liver disease in coinfected patients. To describe
      the clinical, epidemiological, and histopathological aspects of HTLV-1/HCV
      coinfection in Brazil. A cross-sectional study with 23 patients coinfected with
      HCV/HTLV. The control groups consisted of 21 patients monoinfected with HCV and
      20 patients monoinfected with HTLV-1. The cytokine profiles (Th1 and Th2 cell
      responses), clinical, laboratory features, and histopathological aspects were
      examined. The control group for cytokine analysis validation consisted of
      patients monoinfected with HTLV, and a fourth group consisted of healthy blood
      donors. No anthropometric differences present between the three infected groups.
      We observed higher serum concentrations of IFN-gamma in patients coinfected with
      HCV/HTLV-1 than those in HCV monoinfected patients. The HCV/HTLV-1 coinfected
      group also exhibited a higher degree of liver steatosis than the HCV monoinfected
      patients. Results suggest that HCV/HTLV-1 coinfection may result in a different
      pattern of HCV infection due to the immunologic disorders likely associated with
      HTLV-1, but there is no clear evidence of the HTLV role in the natural history of
      HCV infection. J. Med. Virol. 88:1967-1972, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27027483
TI  - Regulating proliferation and differentiation of osteoblasts on poly(l
      lactide)/gelatin composite nanofibers via timed biomineralization.
AB  - Mimicking the natural bone extracellular matrix, biomineralized nanofibers are
      envisioned as good choices for bone regeneration. Herein, composite nanofibers
      composed of poly(L-lactide) (PLLA) and gelatin (50/50, w/w) were electrospun and
      soaked in a modified five times simulated body fluid (SBF) for 6-24 h. Along with
      the soaking time, the amounts of deposited minerals increased, and the minerals
      transformed from dicalcium phosphate dehydrate (DCPD) to hydroxyapatite (HA).
      Mineral dissolution and Ca(2+) ion release of these biomineralized nanofibers
      were investigated by putting them in deionized water or Hank's balanced salt
      solution. MC3T3-E1 osteoblasts were cultured in transwell chambers without
      contacting the materials or on the biomineralized nanofibers directly. In the
      noncontact culture, the released ions were found able to enhance osteogenic
      differentiation more significantly in comparison with cell proliferation. In the
      contact culture, all biomineralized nanofibers demonstrated strong ability in
      promoting both cell proliferation and osteogenic differentiation. Due to the fast
      dissolution of DCPD, the biomineralized nanofibers obtained from short SBF
      soaking was found to be inferior in enhancing osteogenic differentiation. Whereas
      the cells displayed high levels of alkaline phosphatase activity and collagen I
      synthesis when the material had abundant deposition of apatite. The results
      revealed that cell biological behaviors were synergistically influenced by the
      ionic dissolution products, the composition, and the morphology of biomineralized
      nanofibers, which could be regulated by timed biomineralization. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1968-1980, 2016.

PMID- 27027484
TI  - Anisotropic Charge-Carrier Transport in High-Mobility Donor-Acceptor Conjugated
      Polymer Semiconductor Films.
AB  - Many high-performance solution-processable polymer thin-film transistors (PTFTs)
      have been reported. This contribution presents a comparative study of oriented
      films that have been deposited by means of solution shearing (SS) with charge
      carrier transport anisotropy for PTFTs based on a diketopyrrolopyrrole
      thiazolothiazole donor-acceptor copolymer (PDPPTzBT). The maximum field-effect
      mobility of the SS film of PDPPTzBT was 10.00 cm2  V-1  s. We also blended a
      solution of PDPPTzBT with a solution of polystyrene (PS). Solvent vapor annealing
      (SVA) lateral phase separation was adopted to block carrier transport in the
      direction of pi-pi stacking, and further evidence of charge transport anisotropy
      was provided. Highly oriented polymer films will further influence the carrier
      transport anisotropy and promote carrier transport along the backbone, and the
      performance of the field-effect transistor is thus improved.

PMID- 27027485
TI  - A prospective cross-sectional study of anxiety and depression in patients with
      psoriasis in Singapore.
AB  - BACKGROUND: Psoriasis has a negative psychological impact on patients, and may
      have repercussions on treatment outcomes. Despite this, the degree to which
      psoriatic patients suffer from psychiatric disorders has not received much
      attention in Singapore. OBJECTIVE: This prospective cross-sectional study was
      conducted to determine the frequency of anxiety and depression in a cohort of
      Singaporean patients with psoriasis, and explore its relationship with regards to
      physical disease severity and subjective quality of life. METHODS: 100 patients
      aged 21-60 years old who visited the National Skin Centre, Singapore from 2008 to
      2009 were enrolled into the study. Anxiety and depression were quantified using
      the Hospital Anxiety and Depression Scale (HADS). Disease severity was quantified
      with the Psoriasis Area Severity Index (PASI) and quality of life measured with
      the Short Form (36) Health Survey (SF-36). RESULTS: Using the HADS, the mean
      score for anxiety was 6.9 and that for depression was 4.7. An anxiety disorder
      was suggested in 17%, while a depressive disorder was suggested in 15% of the
      study population. All eight domains of the SF-36 were significantly correlated
      with both anxiety and depression scores. Patients with moderate or severe
      psoriasis (on PASI) had worse depression scores than those with mild psoriasis.
      No association was found between anxiety scores and PASI. Neither was any
      significant correlation seen between anxiety and depression scores vs. patients'
      age, monthly income and duration of psoriasis. CONCLUSION: This study
      demonstrates the strong psychiatric morbidity in patients with psoriasis, for
      which further psychiatric evaluation should be considered.

PMID- 27027487
TI  - Blood, blebs and lumen expansion.
AB  - A powerful combination of cell labelling, genetic tools and rapid imaging
      techniques in vivo has now led to a high-resolution description of lumen
      formation during angiogenesis in zebrafish. The study reveals a haemodynamic
      force-driven and myosin-II-dependent cellular mechanism (termed inverse membrane
      blebbing) as the basis for lumen expansion in unicellular and multicellular
      angiogenic sprouts. 

PMID- 27027488
TI  - Multiple cilia suppress tumour formation.
AB  - Primary cilia are cellular structures that have important functions in
      development and disease. The suppression of multiciliate differentiation of
      choroid plexus precursors, and maintenance of a single primary cilium by Notch1,
      is now shown to be involved in choroid plexus tumour formation. 

PMID- 27027486
TI  - The ever-expanding role of HIF in tumour and stromal biology.
AB  - Low oxygen tension (hypoxia) is a hallmark of cancer that influences cancer cell
      function, but is also an important component of the tumour microenvironment as it
      alters the extracellular matrix, modulates the tumour immune response and
      increases angiogenesis. Here we discuss the regulation and role of hypoxia and
      its key transcriptional mediators, the hypoxia-inducible factor (HIF) family of
      transcription factors, in the tumour microenvironment and stromal compartments. 

PMID- 27027489
TI  - The Architecture and Function of Monoclonal Antibody-Functionalized Mesoporous
      Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for
      Cancer Metastatic Chemoprevention.
AB  - The circulating tumor cells (CTCs) existing in cancer survivors are considered
      the root cause of cancer metastasis. To prevent the devastating metastasis
      cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded
      with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell
      adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer
      metastatic preventive agent by targeting CTCs and preventing their adhesion
      invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica
      nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and
      bind colorectal cancer cells in either cell medium or blood through EpCAM
      recognition proven by quantitative flow cytometric detection and free aEpCAM
      competitive assay. The specific binding results in downregulation of the captured
      cells and drives them into G0/G1 phase primarily attributed to the effect of
      aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion
      between cancer cells and endothelial cells, suggesting the combined inhibition
      effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized
      nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit
      lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can
      prevent cancer metastasis by restraining CTC activity and their adhesion-invasion
      to vascular intima.

PMID- 27027490
TI  - Derivation of a prediction model for a diagnosis of depression in young adults: a
      matched case-control study using electronic primary care records.
AB  - BACKGROUND: Approximately 80 000 children and young people in the UK suffer from
      depression, but many are untreated because of poor identification of early
      warning signs and risk factors. AIMS: This study aimed to derive and to
      investigate discrimination characteristics of a prediction model for a first
      recorded diagnosis of depression in young people aged 15-24 years. METHOD: This
      study used a matched case-control method using electronic primary care records.
      Stepwise conditional logistic regression modelling investigated 42 potential
      predictors including symptoms, co-morbidities, social factors and drug and
      alcohol misuse. RESULTS: Of the socio-economic and symptomatic predictors
      identified, the strongest associations were with depression symptoms and other
      psychological conditions. School problems and social services involvement were
      prominent predictors in men aged 15-18 years, work stress in women aged 19-24
      years. CONCLUSION: Our model is a first step in the development of a predictive
      model identifying early warning signs of depression in young people in primary
      care.

PMID- 27027491
TI  - Circle of Willis Collateral During Temporary Internal Carotid Artery Occlusion
      II: Observations From Computed Tomography Angiography.
AB  - INTRODUCTION: The Circle of Willis (CoW) is the most effective collateral
      circulation to the brain during internal carotid artery (ICA) occlusion. Carotid
      stump pressure (CSP) is an established surrogate measure of the cerebral
      collateral circulation. This study aims to use hemodynamic and computed
      tomography angiography measurements to determine the strongest influences upon
      the dependent variable, CSP. These findings could help clinicians noninvasively
      assess the adequacy of the collateral circulation and facilitate surgical risk
      assessment in an outpatient setting. METHODS: CSP and mean arterial pressure were
      measured during carotid endarterectomy or during carotid balloon test occlusion
      in 92 patients. Intracranial arterial diameters were measured on computed
      tomography angiography at 16 different locations. Univariate and multivariate
      analyses were used to determine the key factors associated with CSP. In a
      subgroup of individuals (n=27) with severe (>70% North American Symptomatic
      Carotid Endarterectomy Trial) contralateral stenosis or occlusion, the same
      analysis was performed. RESULTS: The contralateral anterior cerebral artery
      proximal to anterior communicating artery (A1) of the CoW had the strongest
      influence upon CSP, followed by the mean arterial pressure, the contralateral ICA
      diameter, and the anterior communicating artery diameter (R 2=0.364). In the
      subgroup with high-grade contralateral ICA stenosis, the ipsilateral posterior
      communicating artery exerted the strongest influence (R 2=0.620). CONCLUSIONS:
      During ICA occlusion, the anterior CoW dominates in preserving collateral flow,
      especially the contralateral A1 segment. In individuals with high-grade
      contralateral carotid stenosis, the posterior communicating artery calibre
      becomes a dominant influence. The most favourable anatomy consists of large
      contralateral A1 and anterior communicating arteries, and no contralateral
      carotid stenosis.

PMID- 27027492
TI  - Defining a new diagnostic assessment parameter for wound care: Elevated protease
      activity, an indicator of nonhealing, for targeted protease-modulating treatment.
AB  - It is widely accepted that elevated protease activity (EPA) in chronic wounds
      impedes healing. However, little progress has occurred in quantifying the level
      of protease activity that is detrimental for healing. The aim of this study was
      to determine the relationship between inflammatory protease activity and wound
      healing status, and to establish the level of EPA above which human neutrophil
      derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate
      with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from
      four wound centers across the USA to measure HNE and MMP activity. Healing status
      was determined according to percentage reduction in wound area over the previous
      2-4 weeks; this was available for 211 wounds. Association between protease
      activity and nonhealing wounds was determined by receiver operating
      characteristic analysis (ROC), a statistical technique used for visualizing and
      analyzing the performance of diagnostic tests. ROC analysis showed that area
      under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with
      the most reliable wound trajectory information, respectively. For MMP, the
      corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic
      wounds having values of HNE >5 and/or MMP >=13, should be considered wound
      healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic
      test to detect EPA in clinical practice could enable clinicians to identify
      wounds that are nonhealing, thus enabling targeted treatment with protease
      modulating therapies.

PMID- 27027495
TI  - Papers.

PMID- 27027494
TI  - Foreword.

PMID- 27027497
TI  - Systematic Enumeration and Symmetries of Cubane Derivatives.
AB  - The feasibilities of Fujita's unit-subduced-cycle-index (USCI) approach, Fujita's
      proligand method, and Fujita's stereoisogram approach have been demonstrated by
      applying them to cubane derivatives as probes. They provide us with a new set of
      theoretical foundations for comprehensive investigation of geometric and
      stereoisomeric features of stereochemistry. The new set of theoretical
      foundations is based on mathematical formulations so as to explore mathematical
      stereochemistry as a new interdisciplinary field of stereochemistry. 

PMID- 27027498
TI  - Grey-scale sonography and sonoelastography for diagnosing carpal tunnel syndrome.
AB  - Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy of the
      median nerve at wrist level, and is thought to be caused by compression of the
      median nerve in the carpal tunnel. There is no standard quantitative reference
      for the diagnosis of CTS. Grey-scale sonography and sonoelastography (SEL) have
      been used as diagnostic tools. The most commonly agreed findings in grey-scale
      sonography for the diagnosis of CTS is enlargement of the median nerve cross
      sectional area (CSA). Several authors have assessed additional parameters. "Delta
      CSA" is the difference between the proximal median nerve CSA at the pronator
      quadratus and the maximal CSA within the carpal tunnel. The "CSA ratio" is the
      ratio of CSA in the carpal tunnel to the CSA at the mid forearm. These additional
      parameters showed better diagnostic accuracy than CSA measurement alone.
      Recently, a number of studies have investigated the elasticity of the median
      nerve using SEL, and have shown that this also has diagnostic value, as it was
      significantly stiffer in CTS patients compared to healthy volunteers. In this
      review, we summarize the usefulness of grey-scale sonography and SEL in
      diagnosing CTS. 

PMID- 27027500
TI  - Positioning Accuracy in Otosurgery Measured with Optical Tracking.
AB  - OBJECTIVES: To assess positioning accuracy in otosurgery and to test the impact
      of the two-handed instrument holding technique and the instrument support
      technique on surgical precision. To test an otologic training model with optical
      tracking. STUDY DESIGN: In total, 14 ENT surgeons in the same department with
      different levels of surgical experience performed static and dynamic tasks with
      otologic microinstruments under simulated otosurgical conditions. METHODS: Tip
      motion of the microinstrument was registered in three dimensions by optical
      tracking during 10 different tasks simulating surgical steps such as prosthesis
      crimping and dissection of the middle ear using formalin-fixed temporal bone.
      Instrument marker trajectories were compared within groups of experienced and
      less experienced surgeons performing uncompensated or compensated exercises.
      RESULTS: Experienced surgeons have significantly better positioning accuracy than
      novice ear surgeons in terms of mean displacement values of marker trajectories.
      The instrument support and the two-handed instrument holding techniques
      significantly reduce surgeons' tremor. The laboratory set-up presented in this
      study provides precise feedback for otosurgeons about their surgical skills and
      proved to be a useful device for otosurgical training. CONCLUSIONS: Simple tremor
      compensation techniques may offer trainees the potential to improve their
      positioning accuracy to the level of more experienced surgeons. Training in an
      experimental otologic environment with optical tracking may aid acquisition of
      technical skills in middle ear surgery and potentially shorten the learning
      curve. Thus, simulated exercises of surgical steps should be integrated into the
      training of otosurgeons.

PMID- 27027499
TI  - Caregivers' Experiences of Pathways to Care for Seriously Ill Children in Cape
      Town, South Africa: A Qualitative Investigation.
AB  - PURPOSE: Understanding caregivers' experiences of care can identify barriers to
      timely and good quality care, and support the improvement of services. We aimed
      to explore caregivers' experiences and perceptions of pathways to care, from
      first access through various levels of health service, for seriously ill and
      injured children in Cape Town, South Africa, in order to identify areas for
      improvement. METHODS: Semi-structured, qualitative interviews were conducted with
      primary caregivers of children who were admitted to paediatric intensive care or
      died in the health system prior to intensive care admission. Interviews explored
      caregivers' experiences from when their child first became ill, through each
      level of health care to paediatric intensive care or death. A maximum variation
      sample of transcripts was purposively sampled from a larger cohort study based on
      demographic characteristics, child diagnosis, and outcome at 30 days; and
      analysed using the method of constant comparison. RESULTS: Of the 282 caregivers
      who were interviewed in the larger cohort study, 45 interviews were included in
      this qualitative analysis. Some caregivers employed 'tactics' to gain quicker
      access to care, including bypassing lower levels of care, and negotiating or
      demanding to see a healthcare professional ahead of other patients. It was
      sometimes unclear how to access emergency care within facilities; and non-medical
      personnel informally judged illness severity and helped or hindered quicker
      access. Caregivers commonly misconceived ambulances to be slow to arrive, and
      were concerned when ambulance transfers were seemingly not prioritised by illness
      severity. Communication was often good, but some caregivers experienced language
      difficulties and/or criticism. CONCLUSIONS: Interventions to improve child health
      care could be based on: reorganising the reception of seriously ill children and
      making the emergency route within healthcare facilities clear; promoting
      caregivers' use of ambulances and prioritising transfers according to illness
      severity; addressing language barriers, and emphasising the importance of
      effective communication to healthcare providers.

PMID- 27027501
TI  - Non-surgical periodontal treatment in conjunction with 3 or 7 days systemic
      administration of amoxicillin and metronidazole in severe chronic periodontitis
      patients. A placebo-controlled randomized clinical study.
AB  - AIM: To evaluate the effect of 3 or 7 days systemic administration of amoxicillin
      (AMX) and metronidazole (MET) or placebo as adjunct to non-surgical periodontal
      treatment in severe chronic periodontitis patients. METHODS: One hundred and two
      patients with severe chronic periodontitis [e.g. >=1 site with probing pocket
      depth (PD) >= 6 mm per quadrant] were randomly divided into three equally sized
      groups and treated with either scaling and root planing within 24 h (SRP) +
      placebo (Group A) or SRP + AMX + MET (both 500 mg * 3 times daily) for 3 days
      (Group B) or SRP + AMX + MET (both 500 mg * 3 times daily) for 7 days (Group C).
      PD, clinical attachment level (CAL), bleeding on probing (BOP), full-mouth plaque
      scores (FMPS) and gingival bleeding index (GBI) were assessed prior to treatment
      (baseline), and at 3 and 6 months post-treatment. The primary outcome variable
      was the difference (Delta) in the number of sites with PD >= 6 mm. RESULTS:
      Ninety-one patients completed the study. At both 3 and 6 months, all three
      treatment protocols resulted in statistically significant improvements compared
      to baseline for all evaluated clinical parameters (p < 0.001). At 6 months, a
      statistically significantly greater reduction in the mean number of sites with PD
      >= 6 mm was observed in group B (28.62 +/- 15.32 sites) and group C (30.45 +/-
      15.04 sites) compared to the placebo group (17.10 +/- 14.68 sites). Furthermore,
      both the 3- and the 7-day antibiotic regimen resulted in statistically
      significantly higher clinical improvements compared to the placebo group (p <
      0.05). CONCLUSION: The present findings indicate that in patients with severe
      chronic periodontitis, non-surgical periodontal therapy in conjunction with a 3
      or 7 days systemic administration of AMX + MET may lead to significantly greater
      clinical improvements compared to non-surgical therapy alone.

PMID- 27027502
TI  - Quantification of Massive Seasonal Aggregations of Blacktip Sharks (Carcharhinus
      limbatus) in Southeast Florida.
AB  - Southeast Florida witnesses an enormous seasonal influx of upper trophic level
      marine predators each year as massive aggregations of migrating blacktip sharks
      (Carcharhinus limbatus) overwinter in nearshore waters. The narrow shelf and
      close proximity of the Gulf Stream current to the Palm Beach County shoreline
      drive tens of thousands of sharks to the shallow, coastal environment. This
      natural bottleneck provides a unique opportunity to estimate relative abundance.
      Over a four year period from 2011-2014, an aerial survey was flown approximately
      biweekly along the length of Palm Beach County. A high definition video camera
      and digital still camera mounted out of the airplane window provided a continuous
      record of the belt transect which extended 200 m seaward from the shoreline
      between Boca Raton Inlet and Jupiter Inlet. The number of sharks within the
      survey transect was directly counted from the video. Shark abundance peaked in
      the winter (January-March) with a maximum in 2011 of 12,128 individuals counted
      within the 75.6 km(-2) belt transect. This resulted in a maximum density of 803.2
      sharks km(-2). By the late spring (April-May), shark abundance had sharply
      declined to 1.1% of its peak, where it remained until spiking again in January of
      the following year. Shark abundance was inversely correlated with water
      temperature and large numbers of sharks were found only when water temperatures
      were less than 25  degrees C. Shark abundance was also correlated with day of the
      year but not with barometric pressure. Although shark abundance was not
      correlated with photoperiod, the departure of the sharks from southeast Florida
      occurred around the vernal equinox. The shark migration along the United States
      eastern seaboard corresponds spatially and temporally with the spawning
      aggregations of various baitfish species. These baseline abundance data can be
      compared to future studies to determine if shark population size is changing and
      if sharks are restricting their southward migration as global water temperatures
      increase.

PMID- 27027503
TI  - Marking Triatoma brasiliensis, Triatoma pseudomaculata and Rhodnius nasutus
      Nymphs with Trace Elements: Element Persistence and Effects of Marking on Insect
      Mortality.
AB  - BACKGROUND: Field ecologists often rely on mark-release-recapture (MRR)
      experiments to estimate population dynamics parameters for a given species. In
      the case of a medically important taxon, i.e., a disease vector, inferences on
      species survival and dispersal rates are particularly important as they have the
      potential to provide insights into disease transmission dynamics in endemic
      areas. Medical entomologists have traditionally used fluorescent dusts to
      externally mark the cuticle of insects. However, dust marking is usually
      restricted to the adult life stage because immature insects lose the mark when
      they molt. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the efficacy of 13 trace
      elements in marking nymphs of three native Brazilian Chagas disease vectors:
      Triatoma brasiliensis, Triatoma pseudomaculata, and Rhodnius nasutus. Cr and Cu
      were detected in over 97% of T. brasiliensis (34/35 31/31 for Cr and Cu), while
      Cu and Mn were detected in more than 95% of T. pseudomaculata (29/29 for Cu and
      28/29 for Mn) tested 120 days after marking. Only Mn marked over 90% of R.
      nasutus nymphs (38/41). Overall, trace elements had no negative effects on T.
      pseudomaculata longevity, but As-marked T. brasiliensis nymphs (p<0.01), and Cd
      marked R. nasutus nymphs (p<0.01) had significantly shorter lifespan.
      CONCLUSIONS/SIGNIFICANCE: Previous evidence shows that there is little or no
      genetic differentiation between populations at the microgeographic level, which
      often precludes indirect estimations of dispersal capability based on genetic
      markers. In such situations, MRR studies are more suitable as they measure insect
      movement directly from one site to another, instead of effective migration (i.e.
      gene flow). The determination of a reliable and persistent marking method is the
      first step towards the development of meaningful ecological estimates through the
      application of MRR methodology. Here, we have identified trace elements that can
      be used for mark and recapture studies of three triatomine species in Brazil.

PMID- 27027504
TI  - Sexual behaviour in preschool children in the context of intra-parental violence
      and sexual coercion.
AB  - BACKGROUND: Very little is understood about the developmental antecedents of
      sexual behaviour prior to adolescence. AIMS: Our aim was to examine the impact of
      different forms of intimate partner violence on early childhood sexual
      development. METHODS: We used data from an ongoing prospective longitudinal
      cohort study of Canadian families. Intimate partner violence of various kinds was
      measured using a modified version of the Conflict Tactics Scale. Measures of
      child sexual development were based on the Child Sexual Behavior Inventory. Both
      measures relied on parental report. RESULTS: Sexual coercion between parental
      figures, but not physical violence or emotional aggression, was significantly
      associated with intrusive sexual behaviours shown by 3- to 5-year-old children.
      CONCLUSIONS: It may seem unlikely that 3- to 5- year-old children can understand
      that their parents are in a sexually coercive relationship, but our findings
      suggest that they are sufficiently aware of such behaviours when they occur that
      they may start to model their own behaviour on them. Clinicians and social
      workers may need to be more aware of this possibility. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27027505
TI  - CD4 Counts at Entry to HIV Care in Mexico for Patients under the "Universal
      Antiretroviral Treatment Program for the Uninsured Population," 2007-2014.
AB  - In Mexico, public health services have provided universal access to
      antiretroviral therapy (ART) since 2004. For individuals receiving HIV care in
      public healthcare facilities, the data are limited regarding CD4 T-lymphocyte
      counts (CD4e) at the time of entry into care. Relevant population-based estimates
      of CD4e are needed to inform strategies to maximize the impact of Mexico's
      national ART program, and may be applicable to other countries implementing
      universal HIV treatment programs. For this study, we retrospectively analyzed the
      CD4e of persons living with HIV and receiving care at state public health
      facilities from 2007 to 2014, comparing CD4e by demographic characteristics and
      the marginalization index of the state where treatment was provided, and
      assessing trends in CD4e over time. Our sample included 66,947 individuals who
      entered into HIV care between 2007 and 2014, of whom 79% were male. During the
      study period, the male-to-female ratio increased from 3.0 to 4.3, reflecting the
      country's HIV epidemic; the median age at entry decreased from 34 years to 32
      years. Overall, 48.6% of individuals entered care with a CD4<=200 cells/MUl,
      ranging from 42.2% in states with a very low marginalization index to 52.8% in
      states with a high marginalization index, and from 38.9% among individuals aged
      18-29 to 56.5% among those older than 50. The adjusted geometric mean (95%
      confidence interval) CD4e increased among males from 135 (131,142) cells/MUl in
      2007 to 148 (143,155) cells/MUl in 2014 (p-value<0.0001); no change was observed
      among women, with a geometric mean of 178 (171,186) and 171 (165,183) in 2007 and
      2014, respectively. There have been important gains in access to HIV care and
      treatment; however, late entry into care remains an important barrier in
      achieving optimal outcomes of ART in Mexico. The geographic, socioeconomic, and
      demographic differences observed reflect important inequities in timely access to
      HIV prevention, care, and treatment services, and highlight the need to develop
      contextual and culturally appropriate prevention and HIV testing strategies and
      linkage programs. 

PMID- 27027506
TI  - Differentially expressed genes associated with adaptation to different thermal
      environments in three sympatric Cuban Anolis lizards.
AB  - How animals achieve evolutionary adaptation to different thermal environments is
      an important issue for evolutionary biology as well as for biodiversity
      conservation in the context of recent global warming. In Cuba, three sympatric
      species of Anolis lizards (Anolis allogus, A. homolechis and A. sagrei) inhabit
      different thermal microhabitats, thereby providing an excellent opportunity to
      examine how they have adapted to different environmental temperatures. Here, we
      performed RNA-seq on the brain, liver and skin tissues from these three species
      to analyse their transcriptional responses at two different temperatures. In
      total, we identified 400, 816 and 781 differentially expressed genes (DEGs)
      between the two temperatures in A. allogus, A. homolechis and A. sagrei,
      respectively. Only 62 of these DEGs were shared across the three species,
      indicating that global transcriptional responses have diverged among these
      species. Gene ontology (GO) analysis showed that large numbers of ribosomal
      protein genes were DEGs in the warm-adapted A. homolechis, suggesting that the
      upregulation of protein synthesis is an important physiological mechanism in the
      adaptation of this species to hotter environments. GO analysis also showed that
      GO terms associated with circadian regulation were enriched in all three species.
      A gene associated with circadian regulation, Nr1d1, was detected as a DEG with
      opposite expression patterns between the cool-adapted A. allogus and the hot
      adapted A. sagrei. Because the environmental temperature fluctuates more widely
      in open habitats than in forests throughout the day, the circadian
      thermoregulation could also be important for adaptation to distinct thermal
      habitats.

PMID- 27027508
TI  - Influence of vitamin C on the elicitation of allergic contact dermatitis to p
      phenylenediamine.
AB  - BACKGROUND: Hair dyes represent one of the most important causes of allergic
      contact dermatitis resulting from the use of cosmetic products. The principal
      causative chemistry is associated with oxidation products of p-phenylenediamine
      (PPD) and closely related substances. OBJECTIVES: To examine whether prior
      application of the antioxidant vitamin C to the skin was able to reduce the
      cutaneous allergic response to PPD. METHODS: Twenty eight volunteers with a
      proven history of contact allergy to PPD were recruited. Each was tested with a
      range of PPD doses and PPD-containing hair dye on untreated skin and skin
      pretreated for 10 min with a vitamin C formulation. RESULTS: Pretreatment of skin
      sites with vitamin C led to a reduction in the intensity, or even ablation, of
      the cutaneous allergic reaction to PPD in ~75% of cases as compared with
      untreated skin. CONCLUSIONS: The results suggest that treatment of the skin
      adjacent to the hair-bearing area with antioxidant could form part of a strategy
      to reduce the burden of cosmetic allergic contact dermatitis caused by hair
      dyeing.

PMID- 27027507
TI  - Insulin resistance: a new consequence of altered carotid body chemoreflex?
AB  - Metabolic diseases affect millions of individuals across the world and represent
      a group of chronic diseases of very high prevalence and relatively low
      therapeutic success, making them suitable candidates for pathophysiological
      studies. The sympathetic nervous system (SNS) contributes to the regulation of
      energy balance and energy expenditure both in physiological and pathological
      states. For instance, drugs that stimulate sympathetic activity decrease food
      intake, increase resting metabolic rate and increase the thermogenic response to
      food, while pharmacological blockade of the SNS has opposite effects. Likewise,
      dysmetabolic features such as insulin resistance, dyslipidaemia and obesity are
      characterized by a basal overactivation of the SNS. Recently, a new line of
      research linking the SNS to metabolic diseases has emerged with the report that
      the carotid bodies (CBs) are involved in the development of insulin resistance.
      The CBs are arterial chemoreceptors that classically sense changes in arterial
      blood O2 , CO2 and pH levels and whose activity is known to be increased in
      rodent models of insulin resistance. We have shown that selective bilateral
      resection of the nerve of the CB, the carotid sinus nerve (CSN), totally prevents
      diet-induced insulin resistance, hyperglycaemia, dyslipidaemia, hypertension and
      sympathoadrenal overactivity. These results imply that the beneficial effects of
      CSN resection on insulin action and glucoregulation are modulated by target
      related efferent sympathetic nerves through a reflex that is initiated in the
      CBs. It also highlights modulation of CB activity as a putative future
      therapeutic intervention for metabolic diseases.

PMID- 27027509
TI  - Immunoglobulin G4-related disease presenting with prurigo: Circulating T-helper 2
      cells may be involved in the pathogenesis.
AB  - We report a case of immunoglobulin G4-related disease (IgG4-RD) which presented
      with prurigo on the trunk and extremities. A 66-year-old man had a 2-month
      history of itchy erythematous papules on his trunk and extremities. Bilateral
      eyelid swelling and enlargement of the submandibular and parotid glands were also
      observed. Computed tomography revealed pleural thickening and diffuse pancreatic
      enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen
      obtained from an erythematous papule showed a perivascular inflammatory
      infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland
      biopsy revealed an infiltrate of abundant IgG4-positive plasma cells. Treatment
      with prednisolone resulted in improvement of the skin and other lesions along
      with a decrease in IgG4 serum levels. A flow cytometric assay revealed that
      percentages of interleukin (IL)-4- and IL-13-producing CD4(+) T cells were
      markedly higher in the circulation of the IgG4-RD patient than in that of healthy
      subjects. Moreover, those populations dramatically decreased after treatment.
      Thus, prurigo may be a skin manifestation of IgG4-RD and T-helper 2 cells may
      contribute to the pathogenesis. 

PMID- 27027511
TI  - CO2 Responsive Imidazolium-Type Poly(Ionic Liquid) Gels.
AB  - Poly(ionic liquid) (PIL) gels with CO2 stimulus responsiveness have been
      synthesized through the copolymerization of an imidazolium-type ionic liquid
      monomer with 2-(dimethyl amino) ethyl methacrylate. Upon bubbling with CO2 gas,
      the prepared PIL solution is converted to a transparent and stable gel, which can
      be turned back to the initial solution state after N2 bubbling. The reversible
      sol-gel phase transition behavior is proved by the reversible values of viscosity
      and ionic conductivity. The possible mechanism for such a reversible sol-gel
      phase transition is demonstrated by NMR, conductivity, and rheological
      measurements. 

PMID- 27027510
TI  - Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and
      epithelial-mesenchymal transition in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is a highly aggressive tumour subtype
      associated with poor prognosis. The mechanisms involved in TNBC progression
      remains largely unknown. To date, there are no effective therapeutic targets for
      this tumour subtype. Paired-related homeobox 1b (Prrx1b), one of major isoforms
      of Prrx1, has been identified as a new epithelial-mesenchymal transition (EMT)
      inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this
      study, we found that Prrx1b was significantly up-regulated in TNBC and associated
      with tumour size and vascular invasion of breast cancer. Silencing of Prrx1b
      suppressed the proliferation, migration and invasion of basal-like cancer cells.
      Moreover, silencing of Prrx1b prevented Wnt/beta-catenin signaling pathway and
      induced the mesenchymal-epithelial transition (MET). Taken together, our data
      indicated that Prrx1b may be an important regulator of EMT in TNBC cells and a
      new therapeutic target for interventions against TNBC invasion and metastasis.

PMID- 27027512
TI  - Umbelliferone attenuates unpredictable chronic mild stress induced-insulin
      resistance in rats.
AB  - The aim of this study was to investigate whether umbelliferone (Umb) could
      attenuate insulin resistance in unpredictable chronic mild stress (CUMS)-induced
      rats. Behavioral changes were evaluated through sucrose preference test (SPT),
      open-field test, forced swimming test, and tail suspension test (TST), suggesting
      that Umb (20 and 40 mg/kg) could effectively improve depression symptoms. Oral
      glucose tolerance test and serum insulin indicated that Umb attributed to the
      control of blood glucose levels. The phosphorylation of insulin receptor, insulin
      receptor substrate (IRS)-1, glycogen synthase kinase-3beta, PI3K, and Akt was
      increased in Umb (20 and 40 mg/kg) treatment according to Western blot analysis.
      Taken together, the current results suggested the ameliorative effect of Umb
      against insulin resistance in the CUMS-induced rats. (c) 2016 IUBMB Life,
      68(5):403-409, 2016.

PMID- 27027513
TI  - Exploring the maternal and infant continuum - ethnic disparities in infant
      hospital admissions for respiratory disease.
AB  - OBJECTIVE: To investigate maternal and birth-related risk factors associated with
      infant respiratory hospitalisations in New Zealand. METHODS: A Kaupapa Maori
      framed retrospective cohort analysis of public hospital maternal data linked to
      infant data (54,980 births 1995-2009). Primary outcome was rate of
      hospitalisation for respiratory disease in the first year of life. Risk variables
      examined included socioeconomic status (SES), age, smoking, parity, gestation,
      time to hospital discharge, breastfeeding and maternal ethnicity as a potential
      marker of differential exposure to risk factors. RESULTS: Independent risk
      factors for hospitalisation included low maternal SES (rate ratio: 1.33 [95% CI
      1.19-1.49]); smoking (1.3 [1.19-1.41]); parity (2.77 [2.37-3.24]); preterm birth
      (3.14 [2.58-3.83]; 30 compared with 40 weeks); but not breastfeeding (0.99 [0.87
      1.11]). After adjustment for risk factors, respiratory hospitalisations remained
      highest among infants of young Maori women (rate ratio 1.93 [1.46-2.55] at age
      22.5 years) and Pacific women across all maternal age groups (rate ratios 2.43 to
      2.55), compared with infants of European women. CONCLUSIONS: Maternal and birth
      factors are strongly associated with ethnic disparities in infant hospital
      admissions for respiratory disease. IMPLICATIONS: Interventions that begin in
      pregnancy and address risk factors and social determinants of health are needed
      to address these disparities.

PMID- 27027514
TI  - JAM: A Scalable Bayesian Framework for Joint Analysis of Marginal SNP Effects.
AB  - Recently, large scale genome-wide association study (GWAS) meta-analyses have
      boosted the number of known signals for some traits into the tens and hundreds.
      Typically, however, variants are only analysed one-at-a-time. This complicates
      the ability of fine-mapping to identify a small set of SNPs for further
      functional follow-up. We describe a new and scalable algorithm, joint analysis of
      marginal summary statistics (JAM), for the re-analysis of published marginal
      summary statistics under joint multi-SNP models. The correlation is accounted for
      according to estimates from a reference dataset, and models and SNPs that best
      explain the complete joint pattern of marginal effects are highlighted via an
      integrated Bayesian penalized regression framework. We provide both enumerated
      and Reversible Jump MCMC implementations of JAM and present some comparisons of
      performance. In a series of realistic simulation studies, JAM demonstrated
      identical performance to various alternatives designed for single region
      settings. In multi-region settings, where the only multivariate alternative
      involves stepwise selection, JAM offered greater power and specificity. We also
      present an application to real published results from MAGIC (meta-analysis of
      glucose and insulin related traits consortium) - a GWAS meta-analysis of more
      than 15,000 people. We re-analysed several genomic regions that produced multiple
      significant signals with glucose levels 2 hr after oral stimulation. Through
      joint multivariate modelling, JAM was able to formally rule out many SNPs, and
      for one gene, ADCY5, suggests that an additional SNP, which transpired to be more
      biologically plausible, should be followed up with equal priority to the reported
      index.

PMID- 27027515
TI  - Uncovering Local Trends in Genetic Effects of Multiple Phenotypes via Functional
      Linear Models.
AB  - Recent technological advances equipped researchers with capabilities that go
      beyond traditional genotyping of loci known to be polymorphic in a general
      population. Genetic sequences of study participants can now be assessed directly.
      This capability removed technology-driven bias toward scoring predominantly
      common polymorphisms and let researchers reveal a wealth of rare and sample
      specific variants. Although the relative contributions of rare and common
      polymorphisms to trait variation are being debated, researchers are faced with
      the need for new statistical tools for simultaneous evaluation of all variants
      within a region. Several research groups demonstrated flexibility and good
      statistical power of the functional linear model approach. In this work we extend
      previous developments to allow inclusion of multiple traits and adjustment for
      additional covariates. Our functional approach is unique in that it provides a
      nuanced depiction of effects and interactions for the variables in the model by
      representing them as curves varying over a genetic region. We demonstrate
      flexibility and competitive power of our approach by contrasting its performance
      with commonly used statistical tools and illustrate its potential for discovery
      and characterization of genetic architecture of complex traits using sequencing
      data from the Dallas Heart Study. 

PMID- 27027516
TI  - Comparison of Heritability Estimation and Linkage Analysis for Multiple Traits
      Using Principal Component Analyses.
AB  - A disease trait often can be characterized by multiple phenotypic measurements
      that can provide complementary information on disease etiology, physiology, or
      clinical manifestations. Given that multiple phenotypes may be correlated and
      reflect common underlying genetic mechanisms, the use of multivariate analysis of
      multiple traits may improve statistical power to detect genes and variants
      underlying complex traits. The literature, however, has been unclear as to the
      optimal approach for analyzing multiple correlated traits. In this study,
      heritability and linkage analysis was performed for six obstructive sleep apnea
      hypopnea syndrome (OSAHS) related phenotypes, as well as principal components of
      the phenotypes and principal components of the heritability (PCHs) using the data
      from Cleveland Family Study, which include both African and European American
      families. Our study demonstrates that principal components generally result in
      higher heritability and linkage evidence than individual traits. Furthermore, the
      PCHs can be transferred across populations, strongly suggesting that these PCHs
      reflect traits with common underlying genetic mechanisms for OSAHS across
      populations. Thus, PCHs can provide useful traits for using data on multiple
      phenotypes and for genetic studies of trans-ethnic populations. 

PMID- 27027518
TI  - Bayesian Variable Selection in Multilevel Item Response Theory Models with
      Application in Genomics.
AB  - The goal of this paper is to present an implementation of stochastic search
      variable selection (SSVS) to multilevel model from item response theory (IRT). As
      experimental settings get more complex and models are required to integrate
      multiple (and sometimes massive) sources of information, a model that can jointly
      summarize and select the most relevant characteristics can provide better
      interpretation and a deeper insight into the problem. A multilevel IRT model
      recently proposed in the literature for modeling multifactorial diseases is
      extended to perform variable selection in the presence of thousands of covariates
      using SSVS. We derive conditional distributions required for such a task as well
      as an acceptance-rejection step that allows for the SSVS in high dimensional
      settings using a Markov Chain Monte Carlo algorithm. We validate the variable
      selection procedure through simulation studies, and illustrate its application on
      a study with genetic markers associated with the metabolic syndrome. 

PMID- 27027519
TI  - Microbe-like inclusions in tree resins and implications for the fossil record of
      protists in amber.
AB  - During the past two decades, a plethora of fossil micro-organisms have been
      described from various Triassic to Miocene ambers. However, in addition to
      entrapped microbes, ambers commonly contain microscopic inclusions that sometimes
      resemble amoebae, ciliates, microfungi, and unicellular algae in size and shape,
      but do not provide further diagnostic features thereof. For a better assessment
      of the actual fossil record of unicellular eukaryotes in amber, we studied
      equivalent inclusions in modern resin of the Araucariaceae; this conifer family
      comprises important amber-producers in Earth history. Using time-of-flight
      secondary ion mass spectrometry (ToF-SIMS), we investigated the chemical nature
      of the inclusion matter and the resin matrix. Whereas the matrix, as expected,
      showed a more hydrocarbon/aromatic-dominated composition, the inclusions contain
      abundant salt ions and polar organics. However, the absence of signals
      characteristic for cellular biomass, namely distinctive proteinaceous amino acids
      and lipid moieties, indicates that the inclusions do not contain microbial
      cellular matter but salts and hydrophilic organic substances that probably
      derived from the plant itself. Rather than representing protists or their
      remains, these microbe-like inclusions, for which we propose the term
      'pseudoinclusions', consist of compounds that are immiscible with the terpenoid
      resin matrix and were probably secreted in small amounts together with the actual
      resin by the plant tissue. Consequently, reports of protists from amber that are
      only based on the similarity of the overall shape and size to extant taxa, but do
      not provide relevant features at light-microscopical and ultrastructural level,
      cannot be accepted as unambiguous fossil evidence for these particular groups.

PMID- 27027517
TI  - General Framework for Meta-Analysis of Haplotype Association Tests.
AB  - For complex traits, most associated single nucleotide variants (SNV) discovered
      to date have a small effect, and detection of association is only possible with
      large sample sizes. Because of patient confidentiality concerns, it is often not
      possible to pool genetic data from multiple cohorts, and meta-analysis has
      emerged as the method of choice to combine results from multiple studies. Many
      meta-analysis methods are available for single SNV analyses. As new approaches
      allow the capture of low frequency and rare genetic variation, it is of interest
      to jointly consider multiple variants to improve power. However, for the analysis
      of haplotypes formed by multiple SNVs, meta-analysis remains a challenge, because
      different haplotypes may be observed across studies. We propose a two-stage meta
      analysis approach to combine haplotype analysis results. In the first stage, each
      cohort estimate haplotype effect sizes in a regression framework, accounting for
      relatedness among observations if appropriate. For the second stage, we use a
      multivariate generalized least square meta-analysis approach to combine haplotype
      effect estimates from multiple cohorts. Haplotype-specific association tests and
      a global test of independence between haplotypes and traits are obtained within
      our framework. We demonstrate through simulation studies that we control the type
      I error rate, and our approach is more powerful than inverse variance weighted
      meta-analysis of single SNV analysis when haplotype effects are present. We
      replicate a published haplotype association between fasting glucose-associated
      locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and
      Aging Research in Genomic Epidemiology Consortium and we provide more precise
      haplotype effect estimates. 

PMID- 27027520
TI  - Mumia xiangluensis sp. nov., isolated from the rhizosphere of Peucedanum
      praeruptorum Dunn.
AB  - During an investigation of microbial diversity in medicinal herbs, a novel
      actinobacterium, strain NEAU-KD1(T) was isolated from the rhizosphere of
      Peucedanum praeruptorum Dunn collected from Xianglu Mountain in Heilongjiang
      Province, northeast China and characterized using a polyphasic approach. The
      organism was found to have the typical chemotaxonomic and morphological
      characteristics of the genus Mumia. Cells were observed to be non-spore-forming
      and irregular cocci. The cell wall was found to contain LL-diaminopimelic acid as
      the cell wall diamino acid. The whole-cell sugars were detected as galactose and
      rhamnose and the predominant menaquinone was identified as MK-9(H4). The polar
      lipids were found to consist of diphosphatidylglycerol, phosphatidylglycerol,
      phosphoglycolipid and five unidentified phospholipids. The major cellular fatty
      acids were determined to be composed of C16:0, 10-methyl C18:0 and C18:1omega7c.
      The phylogenetic analysis based on 16S rRNA gene sequence also indicated that
      strain NEAU-KD1(T) belongs to the genus Mumia and with high sequence similarity
      to Mumia flava NBRC 109973(T) (97.6 % sequence similarity). The results of DNA
      DNA hybridization and the phenotypic characteristics indicated that strain NEAU
      KD1(T) could be distinguished from its close phylogenetic relative. Thus, strain
      NEAU-KD1(T) can be concluded to represent a novel species of the genus Mumia, for
      which the name Mumia xiangluensis sp. nov. is proposed. The type strain is NEAU
      KD1(T) (=CGMCC 4.7305(T) = DSM 101040(T)). 

PMID- 27027522
TI  - Highly Strained Heterocycles Constructed from Boron-Boron Multiple Bonds and
      Heavy Chalcogens.
AB  - The reactions of a diborene with elemental selenium or tellurium are shown to
      afford a diboraselenirane or diboratellurirane, respectively. These reactions are
      reminiscent of the sequestration of subvalent oxygen and nitrogen in the
      formation of oxiranes and aziridines; however, such reactivity is not known
      between alkenes and the heavy chalcogens. Although carbon is too electronegative
      to affect the reduction of elements with lower relative electronegativity, the
      highly reducing nature of the B-B double bond enables reactions with Se(0) and
      Te(0) . The capacity of multiple bonds between boron atoms to donate electron
      density is highlighted in reactions where diborynes behave as nucleophiles,
      attacking one of the two Te atoms of diaryltellurides, forming salts consisting
      of diboratellurenium cations and aryltelluride anions.

PMID- 27027521
TI  - Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement
      Following Hemicerebellectomy.
AB  - The compensation that follows cerebellar lesions is based on synaptic
      modifications in many cortical and subcortical regions, although its cellular
      mechanisms are still unclear. Changes in glutamatergic receptor expression may
      represent the synaptic basis of the compensated state. We analyzed in rats the
      involvement of glutamatergic system of the cerebello-frontal network in the
      compensation following a right hemicerebellectomy. We evaluated motor
      performances, spatial competencies and molecular correlates in compensated
      hemicerebellectomized rats which in the frontal cortex contralateral to the
      hemicerebellectomy side received injections of anti-NMDA antibodies from patients
      affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized
      rats, the frontal injections of anti-NMDA antibodies elicited a marked
      decompensation state characterized by slight worsening of the motor symptoms as
      well as severe impairment of spatial mnesic and procedural performances.
      Conversely, in the sham-operated group the frontal injections of anti-NMDA
      antibodies elicited slight motor and spatial impairment. The molecular analyses
      indicated that cerebellar compensatory processes were related to a relevant
      rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other
      glutamatergic components) along the entire cortico-cerebellar network. The long
      term maintenance of the rearranged glutamatergic activity plays a crucial role in
      the maintenance of recovered function. 

PMID- 27027523
TI  - Is There Any Difference between Ranibizumab and Aflibercept Injections in Terms
      of Inflammation Measured with Anterior Chamber Flare Levels in Age-Related
      Macular Degeneration Patients: A Comparative Study.
AB  - PURPOSE: To evaluate the inflammatory reaction to intravitreal aflibercept (IVA)
      or ranibizumab (IVR) in patients with age-related macular degeneration (AMD).
      METHODS: A total of 60 eyes of 60 neovascular AMD patients and 30 eyes of 30 age
      matched healthy people as a control group were included in this observational,
      prospective, comparative study. The AMD patients received 1:1 either IVA or IVR.
      Anterior chamber flare was measured with the Kowa FM-600 laser flare meter (Kowa
      Company, Ltd., Tokyo, Japan) at days 0, 1, and 30. The mean flare value and
      standard deviation are expressed as photon counts per millisecond. RESULTS: There
      were 51 (56.7%) men and 39 (43.3%) women, with a mean age of 72.7 +/- 7.5 years.
      Mean aqueous flare values at baseline, day 1 and day 30 were 7.08 +/- 2.44, 7.23
      +/- 2.56, and 6.99 +/- 2.29, respectively, for the IVR group, 6.87 +/- 3.18, 6.86
      +/- 3.19, and 6.53 +/- 2.79, respectively, for the IVA group, and 6.4 +/- 3.29,
      6.41 +/- 3.06, and 6.42 +/- 3.05, respectively, for the control group. There was
      no statistically significant difference in terms of baseline flare values for
      these three groups (p = 0.666). At the 1-day follow-up, a slight but not
      significant increase in flare was observed in the ranibizumab group. However,
      there was no significant change in aqueous flare values in either the ranibizumab
      or the aflibercept-injected patients (p = 0.768 and p = 0.387, respectively) or
      between the groups (p = 0.635). No significant clinical inflammatory reactions
      were noted before or after intravitreal injections of either ranibizumab or
      aflibercept. CONCLUSION: No significant short-term intraocular inflammation was
      noted in the eyes receiving aflibercept or ranibizumab for the treatment of
      neovascular AMD. Although aflibercept has more immunogenic properties than
      ranibizumab, such as having an extra Fc portion and being a larger molecule, it
      is likely that its more potent anti-inflammatory effects prevent it from inducing
      inflammation.

PMID- 27027524
TI  - Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of
      Fecal Microbiota Transplantation in Gastrointestinal Diseases.
AB  - Fecal microbiota transplantation (FMT), a process by which the normal
      gastrointestinal microbiota is restored, has demonstrated extraordinary cure
      rates for Clostridium difficile infection and low recurrence. The community of
      microorganisms within the human gut (or microbiota) is critical to health status
      and functions; therefore, together with the rise of FMT, the gastrointestinal
      microbiota has emerged as a 'virtual' organ with a level of complexity comparable
      to that of any other organ system and capable to compete with powerful known
      antibiotics for the treatment of several disorders. Although treatment protocols,
      donor selection, stool preparation and delivery methods varied widely, with a few
      reports following an identical protocol, FMT has diffused to other areas where
      the alterations of the gut microbiota ecology (or dysbiosis) have been theorized
      to play a causative role, including inflammatory bowel disease (IBD) and
      irritable bowel syndrome (IBS), among several other extra-intestinal disorders
      (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular
      diseases). FMT can be relatively simple to perform, but a number of challenges
      need to be overcome before this procedure is widely accepted in clinical
      practice, and currently, there is no consensus between the various
      gastrointestinal organizations and societies regarding the FMT procedure. In this
      article, we describe the modern high-throughput sequencing techniques to
      characterize the composition of gut microbiota and the potential for therapeutics
      by manipulating microbiota with FMT in several gastrointestinal disorders (C.
      difficile-associated diarrhea, IBD and IBS), with a look on the potential future
      directions of FMT. 

PMID- 27027525
TI  - Adaptive evolution of a derived radius morphology in manakins (Aves, Pipridae) to
      support acrobatic display behavior.
AB  - The morphology of the avian skeleton is often studied in the context of
      adaptations for powered flight. The effects of other evolutionary forces, such as
      sexual selection, on avian skeletal design are unclear, even though birds produce
      diverse behaviors that undoubtedly require a variety of osteological
      modifications. Here, we investigate this issue in a family of passerine birds
      called manakins (Pipridae), which have evolved physically unusual and elaborate
      courtship displays. We report that, in species within the genus Manacus, the
      shaft of the radius is heavily flattened and shows substantial solidification.
      Past work anecdotally notes this morphology and attributes it to the species'
      ability to hit their wings together above their heads to produce loud mechanical
      sonations. Our results show that this feature is unique to Manacus compared to
      the other species in our study, including a variety of taxa that produce other
      sonations through alternate wing mechanisms. At the same time, our data reveal
      striking similarities across species in total radius volume and solidification.
      Together, this suggests that supposedly adaptive alterations in radial morphology
      occur within a conserved framework of a set radius volume and solidness, which in
      turn is likely determined by natural selection. Further allometric analyses imply
      that the radius is less constrained by body size and the structural demands that
      underlie powered flight, compared to other forelimb bones that are mostly
      unmodified across taxa. These results are consistent with the idea that the
      radius is more susceptible to selective modification by sexual selection.
      Overall, this study provides some of the first insight into the osteological
      evolution of passerine birds, as well as the way in which opposing selective
      forces can shape skeletal design in these species. J. Morphol. 277:766-775, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27027526
TI  - Role of Pre-Morbid Factors and Exposure to Blast Mild Traumatic Brain Injury on
      Post-Traumatic Stress in United States Military Personnel.
AB  - Mild traumatic brain injury (mTBI), the signature injury of the recent wars in
      Afghanistan and Iraq, is a prevalent and potentially debilitating condition that
      is associated with symptoms of post-traumatic stress/post-traumatic stress
      disorder (PTS/PTSD). Prior mTBI, severity and type of injury (blast vs. non
      blast), and baseline psychiatric illness are thought to impact mTBI outcomes. It
      is unclear if the severity of pre-morbid PTS/PTSD is a risk factor of post-injury
      levels of PTS and mTBI symptoms. The objective of the study was to examine
      predictors of post-injury PTS/PTSD, including pre-morbid PTS symptoms, and
      physical and cognitive symptoms in the sub-acute phase (1 week-3 months)
      following an acute mTBI. A retrospective review of medical records was performed
      of 276 servicemen assigned to the United States Army Special Operations Command
      referred for mTBI evaluation between December 2009 and March 2011. Post
      Concussion Symptom Scale and PTSD Checklist scores were captured pre- and post
      injury. A total of 276 records were reviewed. Pre-morbid and post-injury data
      were available for 91% (251/276). Of the 54% (136/251) of personnel with mTBI,
      29% (39/136) had positive radiology findings and 11% (15/136) met criteria for
      clinical PTS symptoms at baseline. Logistic regression analysis found baseline
      PTS symptoms predicted personnel who met clinical levels of PTSD. Receiver
      operating characteristic curve analysis revealed that baseline PTS (p = 0.001),
      baseline mTBI symptoms (p = 0.001), and positive radiology (magnetic resonance
      imaging or computed tomography) findings for complicated mTBI (p = 0.02)
      accurately identified personnel with clinical levels of PTSD following mTBI.
      Years of military service, combat deployment status, age, and injury mechanism
      (blast vs. non-blast) were not associated with increased risk of PTS following
      mTBI. Pre-morbid PTS symptoms are associated with an increased risk for clinical
      levels of PTS following a subsequent mTBI. Symptom severity and positive
      radiologic findings may amplify this risk. At-risk personnel may benefit from
      early identification and intervention.

PMID- 27027527
TI  - Bazedoxifene and Conjugated Equine Estrogen: A Combination Product for the
      Management of Vasomotor Symptoms and Osteoporosis Prevention Associated with
      Menopause.
AB  - Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator
      (SERM), has been combined with conjugated equine estrogen (CE) to create a tissue
      selective estrogen complex (TSEC) for the management of vasomotor symptoms (VMS)
      and the prevention of osteoporosis (OP) associated with menopause. Both of these
      outcomes of menopause contribute to significant negative effects on quality of
      life and increases in utilization of health care resources and dollars. Current
      treatment modalities for VMS and OP include estrogen therapy that requires the
      use of progestin in women who have a uterus to reduce the risk of endometrial
      hyperplasia and resultant cancer. However, progestin use results in nuisance
      bleeding as well as a further increased risk of breast cancer when combined with
      estrogen. And while SERMs can be used to prevent OP, their use alone has been
      shown to increase hot flashes. The combination of BZA and CE does not require
      progestin treatment with CE as the BZA component acts as an antagonist on
      endometrial tissue. The U.S. Food and Drug Administration approval of BZA/CE in
      2013 was based on a series of five phase 3 studies known as the Selective
      estrogens, Menopause And Response to Therapy (SMART) trials. These trials, in
      their entirety, evaluated the impact of BZA/CE on VMS frequency and severity,
      bone mineral density, bone turnover markers, vaginal symptoms, lipid profiles,
      sleep, quality of life, breast density, and endometrial safety. The approved dose
      of BZA/CE is 20 mg BZA and 0.45 mg CE. Although this TSEC manages VMS while
      opposing breast and endometrial proliferation, preventing bone resorption, and
      improving lipid profiles, long-term experience with BZA/CE is currently lacking.

PMID- 27027528
TI  - A deep look into a grey optic disc using Spectralis OCT.

PMID- 27027529
TI  - Gluten in infants and celiac disease risk.

PMID- 27027530
TI  - Poor prognosis in human papillomavirus-positive oropharyngeal squamous cell
      carcinomas that overexpress hypoxia inducible factor-1alpha.
AB  - BACKGROUND: Hypoxia induces stabilization of the transcription factor HIF-1alpha
      (HIF-1alpha), associated with (chemo-)radiotherapy resistance in oropharyngeal
      squamous cell carcinoma (SCC). We investigated the effect of HIF-1alpha
      expression on survival in relation to human papillomavirus (HPV) status in
      oropharyngeal SCC. METHODS: We conducted an immunohistochemical analysis of HIF
      1alpha protein expression and downstream targets carbonic anhydrase-IX (CA-IX)
      and glucose transporter-1 (GLUT-1) in 274 patients with oropharyngeal SCC.
      Overall survival (OS) was analyzed in total and stratified for HPV status and
      treatment. RESULTS: In HPV-positive tumors (n = 44), HIF-1alpha overexpression
      predicted worse OS (hazard ratio [HR] = 6.23; p = .012), whereas TNM
      classification or treatment modality did not. In HPV-negative tumors (n = 218),
      advanced T and N classification and HIF-1alpha overexpression all independently
      predicted worse OS. However, the effect of HIF-1alpha overexpression on OS was
      lower in HPV-negative (HR = 1.50; p = .024) than in HPV-positive tumors.
      CONCLUSION: HIF-1alpha overexpression is associated with worse OS and
      characterized a subgroup of patients with HPV-positive oropharyngeal SCC with
      poor prognosis. Possibly, patients with HIF-1alpha overexpressing HPV-positive
      tumors should not be eligible for treatment dose deescalation. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 38: 1338-1346, 2016.

PMID- 27027531
TI  - IFNL4 polymorphism effects on outcome of simeprevir, peginterferon, and ribavirin
      therapy for older patients with genotype 1 chronic hepatitis C.
AB  - AIM: Older patients with chronic hepatitis C have a lower virological response to
      interferon (IFN)-based treatments compared to younger patients. A single
      nucleotide polymorphism in the IFN-lambda-4 (IFNL4) gene has a potent predictive
      effect on treatment response to IFN-based treatments. The efficacy of simeprevir
      (SMV) plus pegylated-IFN (PEG-IFN) and ribavirin therapy and the predictive value
      of IFNL4 on the outcome of therapy for older patients have not been addressed.
      METHODS: This retrospective multicenter study included 234 consecutive Japanese
      patients with genotype 1 chronic hepatitis C. We assessed the predictive factors
      for sustained virological response (SVR) to SMV, PEG-IFN, and ribavirin triple
      therapy in 170 younger (<70 years) and 64 older (>=70 years) patients. IFNL4
      polymorphism ss469415590 was analyzed by Invader assay. RESULTS: The SVR rate for
      older patients was similar to that for younger patients (63.9% and 72.0%,
      respectively). The SVR rate for the IFNL4 TT/TT group was significantly higher
      than the IFNL4 TT/DeltaG or DeltaG/DeltaG group both in younger (93.6% and 46.1%,
      respectively, P < 0.01) and older patients (84.4% and 33.3%, respectively, P <
      0.001). In multivariate regression analysis, IFNL4 TT/TT genotype, response to
      previous treatment and IFNL4 TT/TT genotype were identified as independent
      predictive factors for SVR in older and younger patients, respectively. Decrease
      in hemoglobin level was similar between the two groups. CONCLUSION: The
      virological response to SMV triple therapy in older patients was similar to that
      of younger patients. Analysis of IFNL4 polymorphisms is a valuable predictor in
      both younger and older patients.

PMID- 27027532
TI  - Elucidating population-wide mycobacterial replication dynamics at the single-cell
      level.
AB  - Mycobacterium tuberculosis infections result in a spectrum of clinical outcomes,
      and frequently the infection persists in a latent, clinically asymptomatic state.
      The within-host bacterial population is likely to be heterogeneous, and it is
      thought that persistent mycobacteria arise from a small population of viable, but
      non-replicating (VBNR) cells. These are likely to be antibiotic tolerant and
      necessitate prolonged treatment. Little is known about these persistent
      mycobacteria, since they are very difficult to isolate. To address this, we have
      successfully developed a replication reporter system for use in M. tuberculosis.
      This approach, termed fluorescence dilution, exploits two fluorescent reporters;
      a constitutive reporter allows the tracking of bacteria, while an inducible
      reporter enables the measurement of bacterial replication. The application of
      fluorescence single-cell analysis to characterize intracellular M. tuberculosis
      identified a distinct subpopulation of non-growing mycobacteria in murine
      macrophages. The presence of VBNR and actively replicating mycobacteria was
      observed within the same macrophage after 48 h of infection. Furthermore, our
      results suggest that macrophage uptake resulted in enrichment of non- or slowly
      replicating bacteria (as revealed by d-cycloserine treatment); this population is
      likely to be highly enriched for persisters, based on its drug-tolerant
      phenotype. These results demonstrate the successful application of the novel dual
      fluorescence reporter system both in vitro and in macrophage infection models to
      provide a window into mycobacterial population heterogeneity.

PMID- 27027533
TI  - Solar Irradiance Changes and Phytoplankton Productivity in Earth's Ocean
      Following Astrophysical Ionizing Radiation Events.
AB  - Two atmospheric responses to simulated astrophysical ionizing radiation events
      significant to life on Earth are production of odd-nitrogen species, especially
      NO2, and subsequent depletion of stratospheric ozone. Ozone depletion increases
      incident short-wavelength ultraviolet radiation (UVB, 280-315 nm) and longer
      (>600 nm) wavelengths of photosynthetically available radiation (PAR, 400-700
      nm). On the other hand, the NO2 haze decreases atmospheric transmission in the
      long-wavelength UVA (315-400 nm) and short-wavelength PAR. Here, we use the
      results of previous simulations of incident spectral irradiance following an
      ionizing radiation event to predict changes in terran productivity focusing on
      photosynthesis of marine phytoplankton. The prediction is based on a spectral
      model of photosynthetic response, which was developed for the dominant genera in
      central regions of the ocean (Synechococcus and Prochlorococcus), and on remote
      sensing-based observations of spectral water transparency, temperature, wind
      speed, and mixed layer depth. Predicted productivity declined after a simulated
      ionizing event, but the effect integrated over the water column was small. For
      integrations taking into account the full depth range of PAR transmission (down
      to 0.1% of utilizable PAR), the decrease was at most 2-3% (depending on strain),
      with larger effects (5-7%) for integrations just to the depth of the surface
      mixed layer. The deeper integrations were most affected by the decreased
      utilizable PAR at depth due to the NO2 haze, whereas shallower integrations were
      most affected by the increased surface UV. Several factors tended to dampen the
      magnitude of productivity responses relative to increases in surface-damaging
      radiation, for example, most inhibition in the modeled strains is caused by UVA
      and PAR, and the greatest relative increase in damaging exposure is predicted to
      occur in the winter when UV and productivity are low.

PMID- 27027534
TI  - Corrigendum: Nickel(II) meso-Hydroxyporphyrin Complexes Revisited: Palladium
      Catalysed Synthesis, Electronic Structures of Derived Oxy Radicals, and Oxidative
      Coupling to a Dioxoporphodimethene Dyad.

PMID- 27027536
TI  - Providing leadership on a hidden issue: Where are the mental health nurses?

PMID- 27027537
TI  - A success story in pharmacogenomics: genetic ID card for SJS/TEN.

PMID- 27027538
TI  - Sequence Effect on the Topology of 3 + 1 Interlocked Bimolecular DNA G
      Quadruplexes.
AB  - Electrospray ionization mass spectrometry (ESI-MS) combined with fluorescence,
      circular dichroism, UV spectrophotometer, and native polyacrylamide gel
      electrophoresis techniques are used to study structural features of interlocked
      dimers formed by DNA sequence 93del (GGGGTGGGAGGAGGGT) and its derivatives.
      Herein, we demonstrate that the interlocked dimers can be distinguished from
      stacked dimers formed by sequences T30923 (GGGTGGGTGGGTGGGT) and T30177
      (GTGGTGGGTGGGTGGGT). In addition, loop length, the base at 5'-end, and the
      isolation of T and TT to the first 4G tract do significantly influence the
      formation and topologies of interlocked dimers. Furthermore, our results suggest
      that the 4G tract and the 2G tract in various locations in the 93del derivative
      sequence can form interlocked structure. This work not only provides new insight
      into the assembly of 3 + 1 interlocked DNA conformations but also demonstrates
      that ESI-MS combined with other analytical methods is rapid and useful for DNA
      structural studies.

PMID- 27027540
TI  - Report of the Japan diabetes society/Japanese cancer association joint committee
      on diabetes and cancer, Second report.
AB  - The Japan Diabetes Society/Japanese Cancer Association Joint Committee on
      Diabetes and Cancer published its first report in July 2013 on the
      epidemiological assessment of the associations of diabetes with cancer
      risk/prognosis, the common risk factors for diabetes and cancer, and cancer risk
      associated with diabetes treatment. The Joint Committee continued its work to
      assess the role of glycemic control in the development of cancer in patients with
      diabetes. This review shows that high-quality evidence examining the association
      between glycemic control and cancer risk is lacking.

PMID- 27027542
TI  - Frontal and Parietal Cortices Show Different Spatiotemporal Dynamics across
      Problem-solving Stages.
AB  - Arithmetic problem-solving can be conceptualized as a multistage process ranging
      from task encoding over rule and strategy selection to step-wise task execution.
      Previous fMRI research suggested a frontal-parietal network involved in the
      execution of complex numerical and nonnumerical tasks, but evidence is lacking on
      the particular contributions of frontal and parietal cortices across time. In an
      arithmetic task paradigm, we evaluated individual participants' "retrieval" and
      "multistep procedural" strategies on a trial-by-trial basis and contrasted those
      in time-resolved analyses using combined EEG and MEG. Retrieval strategies relied
      on direct retrieval of arithmetic facts (e.g., 2 + 3 = 5). Procedural strategies
      required multiple solution steps (e.g., 12 + 23 = 12 + 20 + 3 or 23 + 10 + 2).
      Evoked source analyses revealed independent activation dynamics within the first
      second of problem-solving in brain areas previously described as one network,
      such as the frontal-parietal cognitive control network: The right frontal cortex
      showed earliest effects of strategy selection for multistep procedural strategies
      around 300 msec, before parietal cortex activated around 700 msec. In time
      frequency source power analyses, memory retrieval and multistep procedural
      strategies were differentially reflected in theta, alpha, and beta frequencies:
      Stronger beta and alpha desynchronizations emerged for procedural strategies in
      right frontal, parietal, and temporal regions as function of executive demands.
      Arithmetic fact retrieval was reflected in right prefrontal increases in theta
      power. Our results demonstrate differential brain dynamics within frontal
      parietal networks across the time course of a problem-solving process, and
      analyses of different frequency bands allowed us to disentangle cortical regions
      supporting the underlying memory and executive functions. 

PMID- 27027541
TI  - Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults
      with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: The purposes of this study were to examine the impact of 3 weeks of
      amphetamine administration on intrinsic connectome-wide connectivity patterns in
      adults with attention-deficit/hyperactivity disorder (ADHD) and explore the
      association between stimulant-induced symptom improvement and functional
      connectivity alteration. METHODS: Participants included 19 adults (age 20-55
      years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental
      Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician
      Diagnostic Scale taking part in amphetamine trials. For each patient, two 6
      minute resting-state functional magnetic resonance imaging (R-fMRI) scans were
      acquired at baseline and after treatment. A fully data-driven multivariate
      analytic approach (i.e., multivariate distance matrix regression [MDMR]) was
      applied to R-fMRI data to characterize the distributed pharmacological effects in
      the entire functional connectome. Clinical efficacy was assessed using ADHD
      rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom
      Checklist. We linked stimulant-induced functional connectivity changes to symptom
      amelioration using Spearman's correlation. RESULTS: Three weeks of administration
      of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on R-fMRI
      data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive
      control region) and the medial prefrontal cortex (MPFC, the anterior core of
      default network) whose distributed patterns of functional connectivity across the
      entire brain were altered by psychostimulants. Follow-up intrinsic functional
      connectivity revealed that stimulants specifically decreased the positive
      functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex,
      and MPFC-insula. Importantly, these functional connectivity changes are
      associated with symptom improvement. CONCLUSION: These results suggested that
      ADHD is associated with increased functional integration or decreased functional
      segregation between core regions of cognitive control, default, and salience
      networks. The apparent normalization of intrinsic functional interaction in these
      circuits (i.e., increased functional segregation) may underlie the clinical
      benefits produced by 3 weeks of amphetamine treatment.

PMID- 27027543
TI  - Spatiotemporal Dynamics of Morphological Processing in Visual Word Recognition.
AB  - The spatiotemporal dynamics of morphological, orthographic, and semantic
      processing were investigated in a primed lexical decision task in French using
      magnetoencephalography (MEG). The goal was to investigate orthographic and
      semantic contributions to morphological priming and compare these effects with
      pure orthographic and semantic priming. The time course of these effects was
      analyzed in anatomically defined ROIs that were selected according to previous
      MEG and fMRI findings. The results showed that morphological processing was not
      localized in one specific area but distributed over a vast network that involved
      left inferior temporal gyrus, left superior temporal gyrus, left inferior frontal
      gyrus, and left orbitofrontal gyrus. Second, all morphological effects were
      specific, that is, in none of the ROIs could morphology effects be explained by
      pure orthographic or pure semantic overlap. Third, the ventral route was
      sensitive to both the orthographic and semantic "part" of the morphological
      priming effect in the M350 time window. Fourth, the earliest effects of
      morphology occurred in left superior temporal gyrus around 250 msec and reflected
      the semantic contribution to morphological facilitation. Together then, the
      present results show that morphological processing is not just an emergent
      property of processing form or meaning and that semantic contributions to
      morphological facilitation can occur as early as 250 msec in the left superior
      temporal gyrus. 

PMID- 27027544
TI  - Sensory, Cognitive, and Sensorimotor Learning Effects in Recognition Memory for
      Music.
AB  - Recent research suggests that perception and action are strongly interrelated and
      that motor experience may aid memory recognition. We investigated the role of
      motor experience in auditory memory recognition processes by musicians using
      behavioral, ERP, and neural source current density measures. Skilled pianists
      learned one set of novel melodies by producing them and another set by perception
      only. Pianists then completed an auditory memory recognition test during which
      the previously learned melodies were presented with or without an out-of-key
      pitch alteration while the EEG was recorded. Pianists indicated whether each
      melody was altered from or identical to one of the original melodies. Altered
      pitches elicited a larger N2 ERP component than original pitches, and pitches
      within previously produced melodies elicited a larger N2 than pitches in
      previously perceived melodies. Cortical motor planning regions were more strongly
      activated within the time frame of the N2 following altered pitches in previously
      produced melodies compared with previously perceived melodies, and larger N2
      amplitudes were associated with greater detection accuracy following production
      learning than perception learning. Early sensory (N1) and later cognitive (P3a)
      components elicited by pitch alterations correlated with predictions of sensory
      echoic and schematic tonality models, respectively, but only for the perception
      learning condition, suggesting that production experience alters the extent to
      which performers rely on sensory and tonal recognition cues. These findings
      provide evidence for distinct time courses of sensory, schematic, and motoric
      influences within the same recognition task and suggest that learned auditory
      motor associations influence responses to out-of-key pitches. 

PMID- 27027546
TI  - Educating medical students in the era of ubiquitous information.
AB  - Health care around the world is going digital. This inexorable trend will result
      in: (1) routine documentation of care in digital form and emerging national
      infrastructures for sharing data that allow progress toward a learning health
      system; and (2) a biomedical "knowledge cloud" that is fully integrated into
      practice environments and accessible to both providers and consumers of
      healthcare. Concurrently, medical students will be complete digital natives who
      have literally grown up with the Internet and will enter practice early in the
      next decade when the projected changes in practice approach maturity. This essay
      describes three competencies linked to this evolving information environment-(1)
      knowing what you do and don't know, (2) ability to ask a good question, and (3)
      skills in evaluating and weighing evidence-and suggests educational approaches to
      promote student mastery of each competency. Shifting medical education to address
      these competencies will call into question many current methods but may be
      essential to fully prepare trainees for optimal practice in the future. 

PMID- 27027545
TI  - Properties of Cookies Made with Natural Wax-Vegetable Oil Organogels.
AB  - The aim of this study was to examine the feasibility of cookies in which the
      conventional margarine is replaced with an organogel of vegetable oil (VO) and
      natural wax. New cookies from VO organogels contain no trans fats and much less
      saturated fats than cookies made with a conventional margarine. To understand the
      effects of different kinds of waxes, organogels were prepared from 4 different
      waxes including sunflower wax (SW), rice bran wax (RBW), beeswax, and candelilla
      wax and properties of cookie dough and cookie were evaluated. To investigate the
      effects of different VOs on the properties of cookies, 3 VOs including olive oil,
      soybean oil and flaxseed oil representing oils rich in oleic acid (18:1),
      linoleic acid (18:2), and linolenic acid (18:3), respectively, were used. Both
      the wax and VO significantly affected properties of organogel such as firmness
      and melting behavior shown in differential scanning calorimetry. The highest
      firmness of organogel was observed with SW and flaxseed oil. Properties of dough
      such as hardness and melting behavior were also significantly affected by wax and
      VO while trends were somewhat different from those for organogels. SW and RBW
      provided greatest hardnesses to cookie dough. However, hardness, spread factor,
      and fracturability of cookie containing the wax-VO organogel were not
      significantly affected by different waxes and VOs. Several cookies made with wax
      VO organogels showed similar properties to cookies made with a commercial
      margarine. Therefore, this study shows the high feasibility of utilization of the
      organogel technology in real foods such as cookies rich in unsaturated fats. 

PMID- 27027548
TI  - Detecting meaningful body composition changes in athletes using dual-energy x-ray
      absorptiometry.
AB  - Dual-energy x-ray absorptiometry (DXA) imaging is considered to provide a valid
      and reliable estimation of body composition when stringent scanning protocols are
      adopted. However, applied practitioners are not always able to achieve this level
      of control and the subsequent impact on measurement precision is not always taken
      into account when evaluating longitudinal body composition changes. The primary
      aim of this study was to establish the reliability of DXA in an applied elite
      sport setting to investigate whether real body composition changes can be
      detected. Additionally, the performance implications of these changes during the
      training year were investigated. Forty-eight well-trained athletes (from four
      diverse sports) underwent two DXA scans using a 'real-world' approach (with
      limited pre-scan controls), typically within 48 h, to quantify typical error of
      measurement (TEM). Twenty-five athletes underwent further scans, before and after
      specific training and competition blocks. 'True' body composition changes were
      evaluated using 2  *  TEM thresholds. Twelve bob skeleton athletes also performed
      countermovement jump and leg press tests at each time point. Many 'true' body
      composition changes were detected and coincided with the primary training
      emphases (e.g. lean mass gains during hypertrophy-based training). Clear
      relationships (r  +/-  90% CI) were observed between performance changes
      (countermovement jump and leg press) and changes in lean mass (0.53  +/-  0.26
      and 0.35  +/-  0.28, respectively) and fat mass (-0.44  +/-  0.27 and  -0.37  +/-
      0.28, respectively). DXA was able to detect real body composition changes
      without the use of stringent scanning controls. Associations between changes in
      body composition and performance demonstrated the potential influence of these
      changes on strength and power indices. 

PMID- 27027547
TI  - Prulifloxacin vs Levofloxacin for Exacerbation of COPD after Failure of Other
      Antibiotics.
AB  - The chronic course and evolution of chronic obstructive pulmonary disease (COPD)
      is often characterized by periods of exacerbation of symptoms, which have a
      negative impact on the quality of life of patients, as well as on the evolution
      of COPD, and represent a significant cause of medical intervention and
      hospitalization. Very few data are available on the efficacy of rescue
      antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to
      previous treatment. The aim of this study was to evaluate the efficacy of two
      fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR
      study is a randomized, single-blind, non-inferiority comparison between
      levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at
      Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at
      least three points of a global score of symptomatology (maximum score = 15). 258
      patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A
      very high proportion of patients in the two groups had therapeutic success at Day
      10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat;
      94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7
      days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or
      prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in
      17.8% of patients treated with levofloxacin and 14.2% of those receiving
      prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in
      the treatment of AECOPD resistant to other antibiotics.

PMID- 27027549
TI  - Editorial.

PMID- 27027550
TI  - Kinetics and avidity of anti-Toxocara antibodies (IgG) in rabbits experimentally
      infected with Toxocara canis.
AB  - An evaluation was made of the kinetics and avidity of anti-Toxocara antibodies
      (IgG) in rabbits experimentally infected with embryonated Toxocara canis eggs.
      Seventeen four month old New Zealand White rabbits were distributed into two
      groups. In the experimental group, twelve rabbits were infected orally with 1,000
      embryonated T. canis eggs. A second group (n = 5), uninfected, was used as a
      control. Serum samples were collected for analysis on days 7, 14, 21, 28 and 60
      post-infection (DPI). An indirect ELISA test was performed to evaluate the
      reactivity index (RI) of IgG anti-T. canis antibodies and to calculate the
      avidity index (AI). The animals showed seroconversion from the 14th DPI, with
      high AI (over 50%) except for one animal, which presented an intermediate AI. At
      60 DPI, all the animals were seropositive and maintained a high AI. The data
      indicated that specific IgG antibodies formed early (14 DPI) in rabbits infected
      with T. canis, with a high avidity index that persisted throughout the course of
      the infection. 

PMID- 27027551
TI  - Acanthocephala Larvae parasitizing Ameiva ameiva ameiva (Linnaeus, 1758)
      (Squamata: Teiidae).
AB  - Knowledge concerning the taxonomy and biology of species of Acanthocephala,
      helminth parasites of the helminth species of the phylum Acanthocephala,
      parasites of lizards in Brazilian Amazonia, is still insufficient, but reports of
      Acanthocephala in reptiles are becoming increasingly common in the literature.
      Cystacanth-stage Acanthocephalan larvae have been found in the visceral
      peritoneum during necropsy of Ameiva ameiva ameivalizards from the "Osvaldo
      Rodrigues da Cunha" Herpetology Collection of the Emilio Goeldi Museum, Belem,
      Para, Brazil. The aim of this study was to present the morphological study of the
      Acanthocephala larvae found in A. ameiva ameiva lizard. 

PMID- 27027552
TI  - GO-PEG as a drug nanocarrier and its antiproliferative effect on human cervical
      cancer cell line.
AB  - The graphene oxide nanosheets can act as a nanocarrier for the delivery of
      therapeutic agents. The PEGylated GO has high solubility, good stability, and
      more biocompatibility in physiological solutions. In this study, the anticancer
      effects of synthesized GO-PEG as a drug nanocarrier evaluated to estimate the
      synergistic cytotoxic effect of drugs loaded on this type of nanocarrier and to
      determine the actual effect of any drugs encapsulated on it. The cytotoxic
      effects of GO-PEG nanosheets were evaluated on HeLa cell line by MTT assay. The
      results exhibited cytotoxic property of PEGylated GO drug nanocarrier
      significantly is dose dependent and incubation time dependent.

PMID- 27027553
TI  - Update on monitoring and adverse effects of approved second-generation disease
      modifying therapies in relapsing forms of multiple sclerosis.
AB  - PURPOSE OF REVIEW: There has been a considerable increase in the number of
      disease-modifying therapies (DMTs) in recent years. It appears that the number of
      approved DMTs is going to continue to increase in the coming years. The growing
      number of DMTs has provided a challenge to the clinician to tailor their
      therapeutic recommendations based on patients' needs and preferences. To choose
      between these DMTs, knowledge of side-effect profiles is imperative. RECENT
      FINDINGS: Alemtuzumab, a humanized recombinant monoclonal antibody, was recently
      approved for the management of relapsing forms of multiple sclerosis. Its use
      seems to be limited by significant adverse effects and regular monitoring
      requirement. In 2014, the first case of progressive multifocal
      leukoencephalopathy (PML) was diagnosed in a patient with relapsing remitting
      multiple sclerosis who received extended dimethyl fumarate without any
      significant confounding factors. Among patients receiving fingolimod after
      previous natalizumab treatment, there have been 17 suspected cases of PML. There
      have also been three confirmed cases of PML in individuals who received
      fingolimod without previous natalizumab treatment. SUMMARY: In this review, we
      outline the potential adverse effects and recommended laboratory studies as part
      of the monitoring strategy following initiation of various DMTs.

PMID- 27027554
TI  - Beginning of the end of two-stage theory purporting that inflammation then
      degeneration explains pathogenesis of progressive multiple sclerosis.
AB  - PURPOSE OF REVIEW: The review discusses future directions in research on multiple
      sclerosis and neuromyelitis optica, as long-held beliefs about these diseases are
      undermined with data from recent clinical trials. RECENT FINDINGS: Results of
      clinical trials for registration (phase 3) were reported in the last year. Anti
      inflammatory approaches, such as daclizumab high-yield process targeting IL-2
      receptor, and ocrelizumab targeting CD20 B cells, confirmed a beneficial role of
      immune suppression in relapsing-remitting disease. And now for the first time
      achieving the primary end point in primary progressive multiple sclerosis was
      attained with ocrelizumab. SUMMARY: The results in the past year challenge the
      long-held belief that relapsing-remitting disease is inflammatory, whereas
      progressive forms of the disease are 'less inflammatory' and more 'degenerative.'

PMID- 27027555
TI  - Automated continuous vital signs predict use of uncrossed matched blood and
      massive transfusion following trauma.
AB  - BACKGROUND: Recognizing the use of uncross-matched packed red blood cells
      (UnXRBCs) or predicting the need for massive transfusion (MT) in injured patients
      with hemorrhagic shock can be challenging.A validated predictive model could
      accelerate decision making regarding transfusion. METHODS: Three transfusion
      outcomes were evaluated in adult trauma patients admitted to a Level I trauma
      center during a 4-year period (2009-2012): use of UnXRBC, use of greater than 4 U
      of packed red blood cells within 4 hours (MT1), and use of equal to or greater
      than 10 U of packed red blood cells within 24 hours (MT2). Vital sign (VS)
      features including heart rate, systolic blood pressure, and shock index (heart
      rate / systolic blood pressure) were calculated for 5, 10, and 15 minutes after
      admission. Five models were then constructed. Model 1 used preadmission VS, Model
      2 used admission VS, and Models 3, 4, and 5 used continuous VS features after
      admission over 5, 10, and 15 minutes, respectively, to predict the use of UnXRBC,
      MT1, and MT2. Models were evaluated for their predictive performance via area
      under the receiver operating characteristic (ROC) curve, positive predictive
      value, and negative predictive value. RESULTS: Ten thousand six hundred thirty
      six patients with more than 5 million continuous VS data points during the first
      15 minutes after admission were analyzed. Model using preadmission and admission
      VS had similar ability to predict UnXRBC, MT1, or MT2. Compared with these two
      models, predictive ability was significantly improved as duration of VS
      monitoring increased. Continuous VS for 5 minutes had ROCs of 0.83 (confidence
      interval [CI], 0.83-0.84), 0.85 (CI, 0.84-0.86), and 0.86 (CI, 0.85-0.88) to
      predict UnXRBC, MT1, and MT2, respectively. Similarly, continuous VS for 10
      minutes had a ROCs of 0.86 (CI, 0.85--0.86), 0.87 (CI, 0.86-0.88), and 0.88 (CI,
      0.87-0.90) to predict UnXRBC, MT1, and MT2, respectively. Continuous VS for 15
      minutes achieved the highest ROCs of 0.87 (CI, 0.87-0.88), 0.89 (CI, 0.88-0.90),
      and 0.91 (CI, 0.91-0.92) to predict UnXRBC, MT1, and MT2, respectively.
      CONCLUSION: Models using continuous VS collected after admission improve
      prediction for the use of UnXRBC or MT in patients with hemorrhagic shock.
      Decision models derived from automated continuous VS in comparison with single
      prehospital and admission VS identify the use of emergency blood use and can
      direct earlier blood product administration, potentially saving lives. LEVEL OF
      EVIDENCE: Therapeutic study, level III.

PMID- 27027556
TI  - Ingested projectiles: A management dilemma for trauma surgeons.

PMID- 27027558
TI  - Inhibition of platelet function is common following even minor injury.
AB  - BACKGROUND: Hemorrhage remains the leading cause of preventable death following
      injury. Whereas significant attention has been paid to the coagulation cascade,
      there are fewer studies evaluating platelet dysfunction following injury.
      Thrombelastogram platelet mapping (TEG-PM) allows for the measurement of maximal
      potential clot strength and clot strength selectively caused by arachidonic acid
      and adenosine disphosphate receptors on the platelet. The purpose of this study
      was to determine the incidence and magnitude of receptor-specific platelet
      dysfunction following injury in patients who are not otherwise pharmacologically
      anticoagulated. METHODS: A retrospective study of adult trauma patients evaluated
      at a Level I trauma center from August 2013 to September 2014 was conducted.
      Platelet function was assessed using TEG-PM. Patients on any anticoagulant or
      antiplatelet medication were excluded. Patients were divided into those with and
      without radiographically evident traumatic brain injury (TBI). Demographic
      variables, Injury Severity Score (ISS), injury pattern, laboratory test results,
      and mortality were abstracted. Statistical comparisons were made using the
      Student's t test or Mann-Whitney U-test. RESULTS: The study includes 459
      patients, 92% following blunt injury. Median ISS was 5. Patients with TBI (n =
      102) were significantly older (median age, 54 years vs. 35 years), were more
      severely injured (median ISS, 10 vs. 4), had a longer stay and higher mortality
      (9% vs. 0.3%). Maximal potential clot strength was normal in all cohorts, but the
      arachidonic acid and adenosine diphosphate pathways were significantly inhibited
      (30% +/- 26% and 58% +/- 27%, respectively). There was no correlation between TEG
      PM values and ISS, length of stay, or mortality. There was no difference in the
      TBI cohort. There were no significant differences in TEG-PM parameters in those
      with an ISS greater than 14. There was no significant change in TEG-PM following
      platelet transfusion. CONCLUSION: Marked platelet inhibition is common following
      minor injury. Whereas the clinical significance of this finding remains unknown,
      the results of this study should be factored in the overall resuscitative
      strategy. LEVEL OF EVIDENCE: Prognostic/epidemiogic study, level III.

PMID- 27027557
TI  - Intraluminal tranexamic acid inhibits intestinal sheddases and mitigates gut and
      lung injury and inflammation in a rodent model of hemorrhagic shock.
AB  - BACKGROUND: Intravenous tranexamic acid (TXA) is an effective adjunct after
      hemorrhagic shock (HS) because of its antifibrinolytic properties. TXA is also a
      serine protease inhibitor, and recent laboratory data demonstrated that
      intraluminal TXA into the small bowel inhibited digestive proteases and protected
      the gut. A Disintegrin And Metalloproteinase 17 (ADAM-17) and tumor necrosis
      factor alpha (TNF-alpha) are effective sheddases of intestinal syndecan-1, which
      when shed, exposes the underlying intestinal epithelium to digestive proteases
      and subsequent systemic insult. We therefore hypothesized that intraluminal TXA
      as a serine protease inhibitor would reduce intestinal sheddases and syndecan-1
      shedding, mitigating gut and distant organ (lung) damage. METHODS: Mice underwent
      90 minutes of HS to a mean arterial pressure of 35 +/- 5 mm Hg followed by the
      intraluminal administration of TXA or vehicle. After 3 hours, the small
      intestine, lung, and blood were collected for analysis. RESULTS: Intraluminal TXA
      significantly reduced gut and lung histopathologic injury and inflammation
      compared with HS alone. Gut, lung, and systemic ADAM-17 and TNF-alpha were
      significantly increased by HS but lessened by TXA. In addition, gut and lung
      syndecan-1 immunostaining were preserved and systemic shedding lessened after
      TXA. TXA reduced ADAM-17 and TNF-alpha, but not syndecan-1, in TXA-sham animals
      compared with sham vehicles. CONCLUSION: Results of the present study demonstrate
      a beneficial effect of intraluminal TXA in the gut and lung after experimental HS
      in part because of the inhibition of the syndecan-1 shedding by ADAM-17 and TNF
      alpha. Further studies are needed to determine if orally administered TXA could
      provide similar intestinal protection and thus be of potential benefit to
      patients with survivable hemorrhage at risk for organ injury. This is
      particularly relevant in patients or soldiers who may not have access to timely
      medical care.

PMID- 27027559
TI  - Early antithrombotic therapy is safe and effective in patients with blunt
      cerebrovascular injury and solid organ injury or traumatic brain injury.
AB  - BACKGROUND: Early antithrombotic therapy (AT) is the mainstay of treatment in the
      management of blunt cerebrovascular injury (BCVI). Despite this, optimal timing
      of initiation of AT in patients with BCVI in the presence of concomitant
      traumatic brain injury (TBI) or solid organ injury (SOI) remains controversial.
      The purpose of this study was to evaluate the impact of early initiation of AT on
      outcomes in patients with BCVI and TBI and/or SOI. METHODS: Patients with BCVI
      and concomitant TBI and/or SOI over 6 years were identified. Aspirin and/or
      clopidogrel or low-intensity heparin infusion (AT) was instituted in all patients
      immediately upon diagnosis of BCVI. Cessation of AT, worsening TBI, the need for
      delayed operative intervention, ischemic stroke, and mortality were reviewed and
      compared. Worsening of TBI or delayed operative intervention for SOI were
      compared with those of patients without BCVI treated at the same institution
      during the study period. RESULTS: A total of 119 patients (74 with TBI, 26 with
      SOI, and 19 with both) were identified. Seventy-one percent were treated with
      heparin infusion (goal activated partial thromboplastin time, 45-60 seconds), and
      29% received antiplatelet therapy alone. When compared with patients without
      BCVI, there was no difference in worsening of TBI (9% vs. 10% with no BCVI, p =
      0.75) or need for delayed operative intervention for SOI (7% vs. 5% with no BCVI,
      p = 0.61). No patients required cessation of AT. A total of 11 patients (9%)
      experienced a BCVI-related stroke. CONCLUSION: Initiation of early AT for
      patients with BCVI and concomitant TBI or SOI does not increase risk of worsening
      TBI or SOI above baseline. Close monitoring is required, but our results suggest
      that appropriate antiplatelet or heparin therapy should not be withheld in
      patients with BCVI and concomitant TBI or SOI. In fact, prompt treatment with
      either antiplatelet or heparin therapy remains the mainstay for prevention of
      stroke-related morbidity and mortality in these patients. LEVEL OF EVIDENCE:
      Therapeutic/care management study, level IV.

PMID- 27027560
TI  - Gun violence in the United States: A call to action.

PMID- 27027561
TI  - DDT concentration in fish from the Tapajos River in the Amazon region, Brazil.
AB  - DDT and metabolites were measured in six species of fish collected from the
      Tapajos River in the village of Barreiras, near the town of Itaituba in the
      Brazilian Amazon region. The selected fish were the most consumed and
      economically important to the local people. DDT was used frequently in this
      region for malaria control. Fish samples were analyzed after extraction by
      microwave-assisted extraction in hexane/acetone (8:2, v/v) by gas chromatography
      with electron capture detector. Residues of op'-DDT and pp'-DDT and metabolites
      were detected, including pp'-DDE, pp'-DDD, op'-DDT, and op'-DDE, in 98% of the
      samples, with a greater abundance of pp'-DDT. Total DDT levels were 7.1-249.5 ng
      g(-1) wet weight (w.w). The DDE/DDT ratio was low, indicating recent exposure to
      DDT. The study area that may be related to generated waste used in public health
      campaigns to combat mosquitos (Anopheles spp.), still present in the Amazon
      environment, that transmit malaria. DDT levels and metabolites found in fish
      species do not present risks to human health because they are below acceptable
      limits for consumption.

PMID- 27027562
TI  - Evaluation of the removal of antiestrogens and antiandrogens via ozone and
      granular activated carbon using bioassay and fluorescent spectroscopy.
AB  - Antiestrogens and antiandrogens are relatively rarely studied endocrine
      disrupting chemicals which can be found in un/treated wastewaters. Antiestrogens
      and antiandrogens in the wastewater treatment effluents could contribute to
      sexual disruption of organisms. In this study, to assess the removal of non
      specific antiestrogens and antiandrogens by advanced treatment processes,
      ozonation and adsorption to granular activated carbon (GAC), the biological
      activities and excitation emission matrix fluorescence spectroscopy of wastewater
      were evaluated. As the applied ozone dose increased to 12 mg/L, the
      antiestrogenic activity dramatically decreased to 3.2 MUg 4-hydroxytamoxifen
      equivalent (4HEQ)/L, with a removal efficiency of 84.8%, while the antiandrogenic
      activity was 23.1 MUg flutamide equivalent (FEQ)/L, with a removal efficiency of
      75.5%. The removal of antiestrogenic/antiandrogenic activity has high correlation
      with the removal of fulvic acid-like materials and humic acid-like organics,
      suggesting that they can be used as surrogates for antiestrogenic/antiandrogenic
      activity during ozonation. The adsorption kinetics of antiestrogenic activity and
      antiandrogenic activity were well described by pseudo-second-order kinetics
      models. The estimated equilibrium concentration of antiestrogenic activity is 7.9
      MUg 4HEQ/L with an effective removal efficiency of 70.5%, while the equilibrium
      concentration of antiandrogenic activity is 33.7 MUg FEQ/L with a removal
      efficiency of 67.0%. Biological activity evaluation of wastewater effluents is an
      attractive way to assess the removal of endocrine disrupting chemicals by
      different treatment processes. Fluorescence spectroscopy can be used as a
      surrogate measure of bioassays during ozonation.

PMID- 27027563
TI  - Open source non-invasive prenatal testing platform and its performance in a
      public health laboratory.
AB  - OBJECTIVE: The objective of this study was to introduce non-invasive prenatal
      testing (NIPT) for fetal autosomal trisomies and gender in a Danish public health
      setting, using semi-conductor sequencing and published open source scripts for
      analysis. METHODS: Plasma-derived DNA from a total of 375 pregnant women (divided
      into three datasets) was whole-genome sequenced on the Ion ProtonTM platform and
      analyzed using a pipeline based on WISECONDOR for fetal autosomal aneuploidy
      detection and SeqFF for fetal DNA fraction estimation. We furthermore validated a
      fetal sex determination analysis. RESULTS: The pipeline correctly detected 27/27
      trisomy 21, 4/4 trisomy 18, and 3/3 trisomy 13 fetuses. Neither false negatives
      nor false positives (chromosomes 13, 18, and 21) were observed in our validation
      dataset. Fetal sex was identified correctly in all but one triploid fetus
      (172/173). SeqFF showed a strong correlation (R(2)  = 0.72) to Y-chromosomal
      content of the male fetus samples. DISCUSSION: We have implemented NIPT into
      Danish health care using published open source scripts for autosomal aneuploidy
      detection and fetal DNA fraction estimation showing excellent false negative and
      false positive rates. SeqFF provides a good estimation of fetal DNA fraction.
      This coupled with an analysis of fetal sex that provides a complete NIPT
      workflow, which may easily be adapted for implementation in other public health
      laboratories. (c) 2016 John Wiley & Sons, Ltd.

PMID- 27027564
TI  - Validation of an Experimental Model to Study Less Severe Chronic Renal Failure.
AB  - PURPOSE: The 5/6 nephrectomy, mimics the stages of human chronic renal failure
      (CRF), but the procedure causes severe renal functional and morphological damage
      that could interfere with the evaluation of therapies for slowing the progression
      of the disease. This study summarizes the results of renal function, histology,
      and immunohistochemical findings in rats undergoing a 2/3 nephrectomy. METHODS:
      The rats were distributed in groups according to the type of nephrectomy: CRF5/6:
      induced by a 5/6 renal mass reduction and CRF2/3: less severe CRF. The body
      weight and blood pressure were monitored, and the serum creatinine (SCr),
      creatinine clearance (CCr), urine osmolality, and 24-h proteinuria (PT24h) were
      measured. CRF progression was evaluated by the rate of decline of CCr (RCCr).
      Histology and immunohistochemistry were performed in the remnant kidneys.
      Statistical analysis was done by unpaired t-test, and a P-value < 0.05 was taken
      as a statistical significance. RESULTS: Compared to the CRF5/6 group, the CRF2/3
      model had a lower SCr, PT24h, CCr, and variations of the SCr from baseline. The
      disease progression was also significantly slower. The renal histopathological
      findings revealed fewer chronic lesions in rats with CRF2/3. Similarly, we
      observed less macrophage accumulation as well as lower proliferative activity and
      expression of fibronectin and a-smooth muscle-actin in the CRF2/3 model.
      CONCLUSIONS: The CRF2/3 model presented with a pattern of less severe CRF,
      functionally and morphologically, compared to the classical CRF5/6 model, and the
      CRF2/3 model may be useful for evaluating therapeutic interventions that target
      the early stages of CRF.

PMID- 27027565
TI  - Functional effects of cannabinoids during dopaminergic specification of human
      neural precursors derived from induced pluripotent stem cells.
AB  - Among adolescents cannabis is one of the most widely used illicit drugs. In
      adolescence brain development continues, characterized by neuronal maturation and
      synaptic plasticity. The endocannabinoid system plays an important role during
      brain development by modulating neuronal function and neurogenesis. Changes in
      endocannabinoid signaling by Delta9 -tetrahydrocannabinol (THC), the psychoactive
      component of cannabis, might therefore lead to neurobiological changes
      influencing brain function and behavior. We investigated the functional
      maturation and dopaminergic specification of human cord blood-derived induced
      pluripotent stem cell (hCBiPSC)-derived small molecule neural precursor cells
      (smNPCs) after cultivation with the endogenous cannabinoid anandamide (AEA) and
      the exogenous THC, both potent agonists at the cannabinoid 1 receptor (CB1 R).
      Higher dosages of 10-MUM AEA or THC significantly decreased functionality of
      neurons, indicated by reduced ion currents and synaptic activity. A lower
      concentration of 1-MUM THC had no marked effect on neuronal and dopaminergic
      maturation, while 1-MUM AEA significantly enhanced the frequency of synaptic
      activity. As there were no significant effects on DNA methylation in promotor
      regions of genes important for neuronal function, these cannabinoid actions seem
      to be mediated by another than this epigenetic mechanism. Our data suggest that
      there are concentration-dependent actions of cannabinoids on neuronal function in
      vitro indicating neurotoxic, dysfunctional effects of 10-MUM AEA and THC during
      human neurogenesis.

PMID- 27027566
TI  - Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory
      Stimulus.
AB  - RATIONALE: Studies suggest that inappropriate responses to proinflammatory
      stimuli might contribute to inflammation in cystic fibrosis (CF) lungs. However,
      technical challenges have made it difficult to distinguish whether altered
      responses in CF airways are an intrinsic defect or a secondary effect of chronic
      disease in their tissue of origin. The CF pig model provides an opportunity to
      study the inflammatory responses of CF airways at birth, before the onset of
      infection and inflammation. OBJECTIVES: To test the hypothesis that acute
      inflammatory responses are perturbed in porcine CF airways. METHODS: We
      investigated the inflammatory responses of newborn CF and non-CF pig airways
      following a 4-hour exposure to heat-killed Staphylococcus aureus, in vivo and in
      vitro. MEASUREMENTS AND MAIN RESULTS: Following an in vivo S. aureus challenge,
      markers of inflammation were similar between CF and littermate control animals
      through evaluation of bronchoalveolar lavage and tissues. However, transcriptome
      analysis revealed genotype-dependent differences as CF pigs showed a diminished
      host defense response compared with their non-CF counterparts. Furthermore, CF
      pig airways exhibited an increase in apoptotic pathways and a suppression of
      ciliary and flagellar biosynthetic pathways. Similar differences were observed in
      cultured airway epithelia from CF and non-CF pigs exposed to the stimulus.
      CONCLUSIONS: Transcriptome profiling suggests that acute inflammatory responses
      are dysregulated in the airways of newborn CF pigs.

PMID- 27027567
TI  - Evaluation of enzymatic and non-enzymatic antioxidants in seminal plasma of men
      with genitourinary infections, varicocele and idiopathic infertility.
AB  - This study was aimed to assess the antioxidant enzymatic and non-enzymatic
      compounds in semen of infertile men. Seventy-four infertile patients were grouped
      according to their clinical diagnosis: genitourinary infection, varicocele,
      idiopathic infertility. Semen samples of fertile men represent the control. Semen
      characteristics were evaluated by light and transmission electron microscopy
      (TEM). TEM data was quantified with a mathematical formula, which provides
      numerical scores. Spectrophotometric and HPLC methods were used to measure the
      amount of reduced (GSH), oxidised glutathione (GSSG), ascorbic acid (AA) and
      malondialdehyde (MDA, marker of lipid peroxidation) and the activity of
      glutathione reductase, catalase (CAT), glutathione peroxidase. Infertile groups
      showed significantly decreased values of sperm parameters vs. CONTROLS: In
      infection and varicocele groups, the seminal MDA levels were significantly
      increased when compared to controls (p < 0.001), indicating an alteration of
      oxidative status and a peroxidative damage. In infection and varicocele groups,
      AA levels were reduced (p < 0.05) vs. control; in the varicocele group, the GSH
      levels were also decreased (p < 0.05). Significantly higher CAT activity was
      observed in infection and varicocele groups vs. fertile men (p < 0.001 and p <
      0.05 respectively). The GSH/GSSG ratio was significantly decreased in varicocele
      and idiopathic infertility groups vs. control (p < 0.01). The study of the
      alteration of a single parameter of oxidative stress or of the antioxidant system
      may not have a relevant clinical value to estimate male fertilising potential and
      the background of infertility causes, since complex and multifactorial mechanisms
      are involved in different pathologies. In our study, each pathology is
      characterised by a definite pattern of markers such as MDA and enzymatic and non
      enzymatic antioxidant compounds. In the different pathologies related to
      infertility, the identification of the complex of involved parameters could be
      useful in the diagnosis, prognosis and in the choice of a possible treatment such
      as specific antioxidant supplements.

PMID- 27027568
TI  - How to Use a Randomized Clinical Trial Addressing a Surgical Procedure: Users'
      Guide to the Medical Literature.
AB  - Because surgical procedures require clinicians to develop and maintain procedural
      expertise and because blinding in randomized clinical trials of such therapies is
      often challenging, their critical appraisal raises unique issues. Risk of bias of
      trials of surgical procedures increases if investigators fail to rigorously
      conceal allocation and, where possible, to ensure blinding of those involved in
      the trial. Variability in surgeons' expertise can also increase bias and lead to
      important limitations in applicability. To address these issues, this Users'
      Guide to the Medical Literature reviews the use of remote randomization systems,
      blinding, sham-controlled trials, split-body trials, expertise-based trials, and
      mechanistic vs practical trials. Consideration of risk of bias and applicability
      issues will allow clinicians to make optimal use of trials addressing surgical
      procedures.

PMID- 27027569
TI  - Short-Term Outcomes of Three-Port Totally Laparoscopic Distal Gastrectomy in the
      Treatment of Gastric Cancer: Comparison with a Four-Port Approach Using a
      Propensity Score Matching Analysis.
AB  - BACKGROUND: We evaluated the feasibility of a three-port totally laparoscopic
      distal gastrectomy (TLDG) as a reduced port laparoscopic surgery for the
      treatment of early gastric cancer (EGC). MATERIALS AND METHODS: In total, 110
      patients who underwent three-port TLDG (n = 25) and four-port TLDG (n = 85) were
      enrolled. A propensity score matching analysis was used to compensate for the
      differences between the groups in age, gender, body mass index, Eastern
      Cooperative Oncology Group classification, and comorbidity. After the matching,
      operative details, pathological features, and short-term postoperative outcomes
      were compared between groups. RESULTS: By propensity score matching, 25 matched
      pairs were created, and no characteristic difference was observed between the
      groups. Operating time was significantly shorter in the three-port TLDG group
      than in the four-port TLDG group (139.4 +/- 39.4 minutes versus 184.8 +/- 42.1
      minutes, respectively; P < .001). Duration until discharge was significantly
      shorter in the three-port TLDG group than in the four-port TLDG group (8.2 +/-
      5.6 days versus 10.2 +/- 6.6 days, respectively; P < .046). Regarding
      pathological features, including TNM stage, no significant difference was
      observed between the groups. CONCLUSIONS: The three-port TLDG is a practical
      method as a reduced port surgery and has better short-term outcomes than the four
      port TLDG for the treatment of EGC.

PMID- 27027570
TI  - Influence of Salts on the Partitioning of 5-Hydroxymethylfurfural in Water/MIBK.
AB  - This study investigates the influence of electrolytes on the performance of
      extracting 5-hydroxymethylfurfural (HMF) from aqueous media using methyl isobutyl
      ketone (MIBK). For that purpose, liquid-liquid phase equilibria (LLE) of
      quaternary systems containing HMF, water, MIBK and salts were measured at
      atmospheric pressure and 298.15 K. The salts under investigation were composed of
      one of the anions NO(3-), SO4(2-), Cl(-), or CH3COO(-) and of one of the alkali
      cations Li(+), Na(+), or K(+). On the basis of these LLE data, the partition
      coefficient of HMF between the aqueous and the MIBK phase KHMF was determined. It
      could be shown that KHMF significantly depends on the kind and concentration of
      the added salt. Weak electrolytes (e.g., sulfates, acetates) caused salting-out,
      whereas nitrates caused salting-in of HMF to the aqueous phase. Unexpectedly,
      LiCl caused salting-out at low LiCl concentrations and salting-in at LiCl
      concentrations higher than 3 mol/kgH2O. The model electrolyte perturbed-chain
      SAFT (ePC-SAFT) was used to predict the salt influence on the LLE in the
      quaternary systems water/MIBK/HMF/salt in good agreement with the experimental
      data. On the basis of ePC-SAFT, it could be concluded that the different salting
      out/salting-in behavior of the various salts is mainly caused by their different
      tendency to form ion pairs in aqueous solutions.

PMID- 27027571
TI  - Visually impaired individuals, safety perceptions and traumatic events: a
      qualitative study of hazards, reactions and coping.
AB  - PURPOSE: To explore the types of risks and hazards that visually impaired
      individuals face, how they manage potential threats and how reactions to
      traumatic events are manifested and coped with. METHOD: Participants were 17
      visually impaired individuals who had experienced some kind of potentially
      traumatic event. Two focus groups and 13 individual interviews were conducted.
      RESULTS: The participants experienced a variety of hazards and potential threats
      in their daily life. Fear of daily accidents was more pronounced than fear of
      disasters. Some participants reported avoiding help-seeking in unsafe situations
      due to shame at not being able to cope. The ability to be independent was
      highlighted. Traumatic events were re-experienced through a variety of sense
      modalities. Fear of labelling and avoidance of potential risks were recurring
      topics, and the risks of social withdrawal and isolation were addressed.
      CONCLUSIONS: Visual impairment causes a need for predictability and adequate
      information to increase and prepare for coping and self-efficacy. The results
      from this study call for greater emphasis on universal design in order to ensure
      safety and predictability. Fear of being labelled may inhibit people from using
      assistive devices and adequate coping strategies and seeking professional help in
      the aftermath of a trauma. Implications for Rehabilitation Visual impairment
      entails a greater susceptibility to a variety of hazards and potential threats in
      daily life. This calls for a greater emphasis on universal design in public
      spaces to ensure confidence and safety. Visual impairment implies a need for
      predictability and adequate information to prepare for coping and self-efficacy.
      Rehabilitation professionals should be aware of the need for independence and
      self-reliance, the possible fear of labelling, avoidance of help-seeking or
      reluctance to use assistive devices. In rehabilitation after accidents or
      potential traumatizing events, professionals' knowledge about the needs for
      information, training and predictability is crucial. The possibility of social
      withdrawal or isolation should be considered.

PMID- 27027572
TI  - The impact of three recent coal-fired power plant closings on Pittsburgh air
      quality: A natural experiment.
AB  - : Relative to the rest of the United States, the region of southwestern
      Pennsylvania, including metropolitan Pittsburgh, experiences high ambient
      concentrations of fine particulate matter (PM2.5), which is known to be
      associated with adverse respiratory and cardiovascular health impacts. This study
      evaluates whether the closing of three coal-fired power plants within the
      southwestern Pennsylvania region resulted in a significant decrease in PM2.5
      concentration. Both PM2.5 data obtained from EPA ground stations in the study
      region and aerosol optical depth (AOD) data retrieved from the Moderate
      Resolution Imaging Spectroradiometer (MODIS) instruments onboard the Terra and
      Aqua satellites were used to investigate regional air quality from January 2011
      through December 2014. The impact of the plant closings on PM2.5 concentration
      and AOD was evaluated using a series of generalized additive models. The model
      results show that monthly fuel consumption of the Elrama plant, which closed in
      October of 2012, and monthly fuel consumption of both the Mitchell and Hatfield's
      Ferry plants, which closed in October of 2013, were significant predictors of
      both PM2.5 concentration and AOD at EPA ground stations in the study region,
      after controlling for multiple meteorological factors and long-term, region-wide
      air quality improvements. The model's power to predict PM2.5 concentration
      increased from an adjusted R2 of 0.61 to 0.68 after excluding data from ground
      stations with higher uncertainty due to recent increases in unconventional
      natural gas extraction activities. After preliminary analyses of mean PM2.5
      concentration and AOD showed a downward trend following each power plant
      shutdown, results from a series of generalized additive models confirmed that the
      activity of the three plants that closed, measured by monthly fuel consumption,
      was highly significant in predicting both AOD and PM2.5 at 12 EPA ground
      stations; further research on PM2.5 emissions from unconventional natural gas
      extraction is needed. IMPLICATIONS: With many coal-fired power plants scheduled
      to close across the United States in the coming years, there is interest in the
      potential impact on regional PM2.5 concentrations. In southwestern Pennsylvania,
      recent coal-fired power plant closings were coupled with a boom in unconventional
      natural gas extraction. Natural gas is currently seen as an economically viable
      bridge fuel between coal and renewable energy. This study provides policymakers
      with more information on the potential ambient concentration changes associated
      with coal-fired power plant closings as the nation's energy reliance shifts
      toward natural gas.

PMID- 27027573
TI  - CXCR2-Mediated Granulocytic Myeloid-Derived Suppressor Cells' Functional
      Characterization and Their Role in Maternal Fetal Interface.
AB  - To investigate CXC chemokine receptor 2 (CXCR2)-mediated granulocytic myeloid
      derived suppressor cells' (MDSCs) (G-MDSCs) functional characterization and their
      role in maternal-fetal interface. Proportions of CXCR2(+) MDSCs and CXCR2 protein
      levels in total MDSCs were lower in abortion-prone CBA/J*DBA/2 mice than in
      CBA/J*BALB/c mice with normal pregnancy. Treatment with CXCR2 neutralizing
      antibody in vivo at early stage of pregnancy significantly increased the embryo
      resorption rates and reduced MDSCs abundance in mice from CBA/J*BALB/c matings.
      Adoptive transfer of MDSCs improved pregnancy outcomes in anti-CXCR2-pretreated
      CBA/J mice in CBA/J*BALB/C matings. CXCR2 was capable of enhancing the migration
      of G-MDSCs efficiently instead of monocytic MDSCs (M-MDSCs). In addition to
      preferential G-MDSC accumulation, arginase I expression as well as arginase I
      activity of G-MDSCs were regulated by CXCR2. CXCL1, as one of CXCR2 ligands,
      correlated well with CXCR2-mediated G-MDSCs migration and arginase I activity.
      CXCR2/CXCL1 axis promotes G-MDSC recruitment and facilitates arginase I
      expression and activity of these cells at maternal-fetal interface. These
      findings provide comprehensive insights into how G-MDSCs are recruited to
      decidual tissues and how local G-MDSCs maintain pregnancy tolerance. 

PMID- 27027574
TI  - Solid-phase synthesis of Rhodamine-110 fluorogenic substrates and their
      application in forensic analysis.
AB  - A novel synthetic route for the rapid and efficient preparation of fluorogenic
      substrates utilizing Rhodamine-110 or similar fluorophores is reported.
      Applicability of the synthesized peptide substrate within a forensic casework
      context is also presented. 

PMID- 27027575
TI  - Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project.
AB  - The primary health care approach advanced at Alma Ata to address social
      determinants of health was replaced by selective health care a year later at
      Bellagio. Subsequently, immunization was endorsed as a cost-effective technical
      intervention to combat targeted infectious diseases. Multilateral efforts to
      collaborate on immunization as a universal public health good ambiguously capture
      the interests of the world's governments as well as private, public, and not-for
      profit institutions. Global assemblages of scientists, governments, industry and
      nongovernmental organizations now work in public-private partnerships to develop
      and make essential vaccines accessible, with vaccines marketed as single fix
      solutions for global health. Drawing from ethnographic fieldwork in France and
      Burkina Faso that followed the development, regulation, and implementation of the
      group A meningococcal conjugate vaccine for sub-Saharan Africa, in this article I
      describe events during and after the development of MenAfriVac. A technological
      success narrative steeped in collaborative capitalist rhetoric disguises
      neglected health care systems.

PMID- 27027576
TI  - Oliguria without serum creatinine increase after living donor liver
      transplantation is associated with adverse post-operative outcomes.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication after liver
      transplantation and is associated with significant morbidity and mortality.
      Although clinical guidelines recommend defining AKI based on serum creatinine
      increase and oliguria, the validity and utility of the oliguric component of AKI
      definition remains largely unexplored. This study examined the incidence and the
      impact on clinical outcomes of oliguria meeting the urine output criterion of AKI
      in patients undergoing liver transplantation. The authors hypothesised that
      oliguria was an independent risk factor for adverse post-operative outcomes.
      METHODS: This study retrospectively examined 320 patients who underwent living
      donor liver transplantation at our centre. AKI stages were allocated according to
      recent guidelines based on serum creatinine or urine output within 7 days of
      surgery. RESULTS: The incidence of oliguria meeting the urine output criterion of
      AKI was 50.3%. Compared with creatinine criterion alone, incorporating oliguria
      into the diagnostic criteria dramatically increased the measured incidence of AKI
      from 39.7% to 62.2%. Compared with patients diagnosed without AKI using either
      criterion, oliguric patients without serum creatinine increase had significantly
      longer intensive care unit stays (median: 5 vs. 4 days, P = 0.016), longer
      hospital stays (median: 60 vs. 49 days, P = 0.014) and lower chronic kidney
      disease-free survival rate on post-operative day 90 (54.2% vs. 73.3%, P = 0.008).
      CONCLUSION: Oliguria is common after liver transplantation, and incorporating
      oliguria into the diagnostic criteria dramatically increases the measured
      incidence of AKI. Oliguria without serum creatinine increase was significantly
      associated with adverse post-operative outcomes.

PMID- 27027577
TI  - Cell polarity is on PAR with cytokinesis.

PMID- 27027579
TI  - Examining the Roles of Work Autonomous and Controlled Motivations on Satisfaction
      and Anxiety as a Function of Role Ambiguity.
AB  - Past research in the self-determination theory has shown that autonomous
      motivation is associated with positive outcomes (e.g., work satisfaction),
      whereas controlled motivation is related to negative outcomes (e.g., anxiety).
      The purpose of the present research was to examine the moderating function of
      role ambiguity on the relationships between work autonomous and controlled
      motivations on the one hand, and work satisfaction and anxiety on the other. Six
      hundred and ninety-eight workers (449 men and 249 women) participated in this
      study. Results revealed that autonomous motivation was most strongly related to
      satisfaction when ambiguity was low. In addition, controlled motivation was most
      strongly related to anxiety when ambiguity was high. In other words, the present
      findings suggest that the outcomes associated with each form of motivation may
      vary as a function of role ambiguity. The present study thus offers meaningful
      insights for organizations, managers, and employees. 

PMID- 27027580
TI  - Atrial Heterogeneous Autonomic Neural Remodeling in Rabbits with Experimental
      Atrial Fibrillation and the Effect of Intervention by Rosuvastatin.
AB  - BACKGROUND: The study aimed to observe the effects of pacing on the atrial
      effective refractory period (AERP), inducibility of atrial fibrillation (AF), and
      changes of atrial autonomic neural remodeling (ANR) by rosuvastatin intervention
      on the acute model of rapid-pacing-induced AF. METHODS: Thirty rabbits were
      randomly divided into a control group (C, n = 10), rapid-pacing group (P, n =
      10), and rosuvastatin-intervention group (R, n = 10). AERP and inducibility of AF
      were measured for all groups. The sympathetic and parasympathetic nerves of left
      atrium, right atrium, and atrial septum labeled with tyrosine hydroxylase (TH)
      and choline acetyl transferase (ChAT) were detected by immunohistochemistry and
      Western blot. RESULTS: The AERP in group R was prolonged, and AF could not be
      induced as easily (P < 0.05). Immunohistochemistry showed that the densities and
      heterogeneity of TH and ChAT positive nerves of the atrium in group P were
      significantly higher than those in group C (ranked as right atrium > atrial
      septum > left atrium), whereas those in group R were decreased (P < 0.05).
      Western blot showed that TH and ChAT protein expression in group P was
      significantly increased compared with group C, but decreased in group R (P <
      0.05). CONCLUSIONS: Persistent rapid atrial pacing can lead to heterogeneous ANR
      in different parts of the rabbit atrium and may cause AF, which can be reversed
      by rosuvastatin. The inhibitory function of rosuvastatin may be associated with
      its role in reversing atrial ANR.

PMID- 27027581
TI  - l-Glutathione enhances antioxidant capacity of hyaluronic acid and modulates
      expression of pro-inflammatory cytokines in human fibroblast-like synoviocytes.
AB  - Intra-articular injection of hyaluronic acid (HA) has been widely accepted for
      the treatment of osteoarthritis (OA) in early stage. l-Glutathione (GSH), an
      antioxidant, has an anti-inflammatory effect on protecting cells from reactive
      oxygen species and reactive nitrogen species (ROS/RNS). In this study, the
      therapeutic effects of HA (0.1%) supplemented with GSH (0, 5, 10, and 20% in
      weight ratios to HA) on human fibroblast-like synoviocytes (FLSs) were evaluated.
      The results showed that cell morphology and glycosaminoglycan production of FLSs
      were not changed under treatments. However, the addition of HA + 20% GSH
      significantly decreased cell survival (p < 0.001) relative to other groups.
      Relative to un-stimulated FLSs, interleukin-1 beta (IL-1beta) stimulation
      significantly decreased the total antioxidant capacity (p < 0.001) of cells. The
      antioxidant capacity was restored and the intracellular ROS/RNS was decreased in
      HA or HA + GSH-treated FLSs. Real-time PCR analysis revealed the mRNA levels of
      IL-1beta, tumor necrosis factor-alpha, and matrix metalloproteinase-3 were down
      regulated significantly (all p < 0.05) when FLSs cultured in HA or HA + GSH. IL-6
      mRNA expressions were down-regulated significantly in HA and HA + 5% GSH groups
      (both p < 0.05) but up-regulated when HA supplemented with 10% and 20% GSH (both
      p < 0.01). In addition, the protein levels of IL-1beta were further decreased
      with significant differences (both p < 0.05) in the HA + 10% GSH and HA + 20% GSH
      groups when compared to FLSs cultured in normal medium. In conclusion, HA
      supplemented with GSH improves antioxidant capacity and modulates pro
      inflammatory cytokines expressions in FLSs. GSH has the potential to augment the
      effect of viscosupplementation using HA on OA patients. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2071-2079, 2016.

PMID- 27027582
TI  - An evaluation of exact methods for the multiple subset maximum cardinality
      selection problem.
AB  - The maximum cardinality subset selection problem requires finding the largest
      possible subset from a set of objects, such that one or more conditions are
      satisfied. An important extension of this problem is to extract multiple subsets,
      where the addition of one more object to a larger subset would always be
      preferred to increases in the size of one or more smaller subsets. We refer to
      this as the multiple subset maximum cardinality selection problem (MSMCSP). A
      recently published branch-and-bound algorithm solves the MSMCSP as a partitioning
      problem. Unfortunately, the computational requirement associated with the
      algorithm is often enormous, thus rendering the method infeasible from a
      practical standpoint. In this paper, we present an alternative approach that
      successively solves a series of binary integer linear programs to obtain a
      globally optimal solution to the MSMCSP. Computational comparisons of the methods
      using published similarity data for 45 food items reveal that the proposed
      sequential method is computationally far more efficient than the branch-and-bound
      approach. 

PMID- 27027583
TI  - Revisiting Surface Modification of Graphite: Dual-Layer Coating for High
      Performance Lithium Battery Anode Materials.
AB  - Surface modification of electrode active materials has garnered considerable
      attention as a facile way to meet stringent requirements of advanced lithium-ion
      batteries. Here, we demonstrated a new coating strategy based on dual layers
      comprising antimony-doped tin oxide (ATO) nanoparticles and carbon. The ATO
      nanoparticles are synthesized via a hydrothermal method and act as electronically
      conductive/electrochemically active materials. The as-synthesized ATO
      nanoparticles are introduced on natural graphite along with citric acid used as a
      carbon precursor. After carbonization, the carbon/ATO-decorated natural graphite
      (c/ATO-NG) is produced. In the (carbon/ATO) dual-layer coating, the ATO
      nanoparticles coupled with the carbon layer exhibit unprecedented synergistic
      effects. The resultant c/ATO-NG anode materials display significant improvements
      in capacity (530 mA h g(-1) ), cycling retention (capacity retention of 98.1 %
      after 50 cycles at a rate of C/5), and low electrode swelling (volume expansion
      of 38 % after 100 cycles) which outperform that of typical graphite materials.
      Furthermore, a full-cell consisting of a c/ATO-NG anode and an LiNi0.5 Mn1.5 O4
      cathode presents excellent cycle retention (capacity retention of >80 % after 100
      cycles). We envision that the dual-layer coating concept proposed herein opens a
      new route toward high-performance anode materials for lithium-ion batteries.

PMID- 27027584
TI  - Factors influencing patient satisfaction: assessment in outpatients in
      dermatology department.
AB  - BACKGROUND: Improving patient satisfaction may lead to better adherence with
      treatment and consequently to better clinical outcomes for skin diseases.
      OBJECTIVES: The aim of this study was to determine factors influencing patient
      satisfaction in consultations with dermatologists. METHODS: All patients
      presenting to the secretariat for a medical consultation received a one-page
      anonymous questionnaire to fill at the end of the consultation. RESULTS: Two
      hundred forty-seven questionnaires were completed. Mean age of the population was
      43.6 years with 58.4% of women and 41.6% of men in the sample. Patients were
      generally satisfied with their consultation (77.1%). Patient age was signifcantly
      related to overall satisfaction (P < 0.01), with greater satisfaction among
      patients aged 50 years and older. The factors that infuence overall satisfaction
      the most were quality of life, physician's concerning, interest in the medical
      problem and attention given to symptoms. Performance of a full-body skin
      examination, use of dermatoscopy, performance of a skin biopsy and comfort of the
      waiting room were additional factors contributing to satisfaction among patients
      50 years and older. CONCLUSIONS: Interpersonal skills of dermatologists and
      attention to the quality of life are important factors in outpatient
      satisfaction.

PMID- 27027585
TI  - iCOBRA: open, reproducible, standardized and live method benchmarking.

PMID- 27027586
TI  - Cancer: hunting rare somatic mutations.

PMID- 27027587
TI  - Overcoming obstacles in localization microscopy.

PMID- 27027588
TI  - Ultrasound-assisted magnetic dispersive solid-phase microextraction: A novel
      approach for the rapid and efficient microextraction of naproxen and ibuprofen
      employing experimental design with high-performance liquid chromatography.
AB  - A simple, rapid, and sensitive method for the determination of naproxen and
      ibuprofen in complex biological and water matrices (cow milk, human urine, river,
      and well water samples) has been developed using ultrasound-assisted magnetic
      dispersive solid-phase microextraction. Magnetic ethylendiamine-functionalized
      graphene oxide nanocomposite was synthesized and used as a novel adsorbent for
      the microextraction process and showed great adsorptive ability toward these
      analytes. Different parameters affecting the microextraction were optimized with
      the aid of the experimental design approach. A Plackett-Burman screening design
      was used to study the main variables affecting the microextraction process, and
      the Box-Behnken optimization design was used to optimize the previously selected
      variables for extraction of naproxen and ibuprofen. The optimized technique
      provides good repeatability (relative standard deviations of the intraday
      precision 3.1 and 3.3, interday precision of 5.6 and 6.1%), linearity (0.1-500
      and 0.3-650 ng/mL), low limits of detection (0.03 and 0.1 ng/mL), and a high
      enrichment factor (168 and 146) for naproxen and ibuprofen, respectively. The
      proposed method can be successfully applied in routine analysis for determination
      of naproxen and ibuprofen in cow milk, human urine, and real water samples. 

PMID- 27027589
TI  - Simultaneous determination of flupyradifurone and its two metabolites in fruits,
      vegetables, and grains by a modified quick, easy, cheap, effective, rugged, and
      safe method using ultra high performance liquid chromatography with tandem mass
      spectrometry.
AB  - An effective analytical method for the simultaneous determination of a novel
      insecticide flupyradifurone and its two metabolites was developed using ultra
      high performance liquid chromatography with tandem mass spectrometry coupled with
      a quick, easy, cheap, effective, rugged, and safe procedure. The three target
      compounds were extracted with acetonitrile and cleaned up with octadecylsilane,
      and were separated successfully between 1.9 and 3.1 min using an HSS T3
      chromatographic column connected to an electrospray ionization source. All the
      matrix-matched samples at three fortified levels (0.01, 0.05, and 0.5 mg/kg)
      provided satisfactory recoveries in the range of 70.3-116.5% with relative
      standard deviations below 18.6%. The limits of quantitation were 10 MUg/kg for
      flupyradifurone and difluoroethylamino-furanone and 100 MUg/kg for 6
      chloronicotinic acid. The limit of quantification of flupyradifurone was far
      below the maximum residue limit in the USA. The method is of great significance
      for establishing maximum residue limits in China. 

PMID- 27027590
TI  - Systematic screening and characterization of astragalosides in an oral solution
      of Radix Astragali by liquid chromatography with quadrupole time-of-flight mass
      spectrometry and Peakview software.
AB  - Liquid chromatography with quadrupole time-of-flight mass spectrometry coupled
      with automated data analysis by Peakview software was employed to systematically
      screen and characterize the astragalosides in Radix Astragali, a Chinese medical
      preparation. The separation was performed on a poroshell 120 SB-C18 column
      equipped in a conventional liquid chromatography system. After being separated
      using a general gradient elution, the analytes were detected by the triple
      quadrupole time-of-flight mass spectrometer in both positive- and negative-ion
      modes. The mass defect filtering function built in the Peakview software was
      utilized to rapidly screen the potential ions of interest, while some functions
      of Peakview such as Formula Finder, XIC manager, and IDA Explorer were employed
      to facilitate the assignment or characterization of the screened astragalosides.
      A total of 42 astragalosides were screened and tentatively characterized or
      assigned, and 20 of them were firstly detected in Radix Astragali. According to
      the screened astragalosides, acetylation, glycosidation, hydrogenation,
      oxidation, and hydration were considered to be the major secondary metabolic
      pathways involved in the formation of the astragalosides. The combination of
      liquid chromatography with quadrupole time-of-flight mass spectrometry and
      automated Peakview analysis is a feasible and efficient tool to screen and
      identify the constituents in complex matrices of herbal medicines. 

PMID- 27027591
TI  - Preparation of cyclodextrin-modified monolithic hybrid columns for the fast
      enantioseparation of hydroxy acids in capillary liquid chromatography.
AB  - Cyclodextrins and their derivatives are one of the most common and successful
      chiral selectors. However, there have been few publications about the use of
      cyclodextrin-modified monoliths. In this study, organic hybrid monoliths were
      prepared by the immobilization of derivatized beta-cyclodextrin alone or with l-2
      allylglycine hydrochloride to the polyhedral oligomeric silsesquioxane methacryl
      substituted monolith. The main topic of this study is a combined system with dual
      chiral selectors (l-2-allylglycine hydrochloride and beta-cyclodextrin) as
      monolithic chiral stationary phase. The effect of l-2-allylglycine hydrochloride
      concentration on enantioseparation was investigated. The enantioseparation of the
      four acidic compounds with resolutions up to 2.87 was achieved within 2.5 min on
      the prepared chiral monolithic column in capillary liquid chromatography.
      Moreover, the possible mechanism of enantioseparation was discussed. 

PMID- 27027592
TI  - Agarose- and alginate-based biopolymers for sample preparation: Excellent green
      extraction tools for this century.
AB  - Recently, there has been considerable interest in the use of miniaturized sample
      preparation techniques before the chromatographic monitoring of the analytes in
      unknown complex compositions. The use of biopolymer-based sorbents in solid-phase
      microextraction techniques has achieved a good reputation. A great variety of
      polysaccharides can be extracted from marine plants or microorganisms. Seaweeds
      are the major sources of polysaccharides such as alginate, agar, agarose, as well
      as carrageenans. Agarose and alginate (green biopolymers) have been manipulated
      for different microextraction approaches. The present review is focused on the
      classification of biopolymer and their applications in multidisciplinary
      research. Besides, efforts have been made to discuss the state-of-the-art of the
      new microextraction techniques that utilize commercial biopolymer interfaces such
      as agarose in liquid-phase microextraction and solid-phase microextraction. 

PMID- 27027593
TI  - Disposable pipette tips extraction: Fundamentals, applications and state of the
      art.
AB  - Disposable pipette tips extraction consists of a solid-phase extraction in which
      the sorbent is poorly dispersed in a pipette tip, which allows a quick and
      dynamic contact between the aspirated analyte from the sample and the solid
      phase. It is a technique used particularly in food and forensic analysis, since
      it requires a small amount of sample and solvent. This article highlights the
      principles, advantages and disadvantages of the disposable pipette tips
      extraction method and reviews recent applications. 

PMID- 27027594
TI  - Rapid analysis of pesticide residues in drinking water samples by dispersive
      solid-phase extraction based on multiwalled carbon nanotubes and pulse glow
      discharge ion source ion mobility spectrometry.
AB  - An analytical method based on dispersive solid-phase extraction with a
      multiwalled carbon nanotubes sorbent coupled with positive pulse glow discharge
      ion mobility spectrometry was developed for analysis of 30 pesticide residues in
      drinking water samples. Reduced ion mobilities and the mass-mobility correlation
      of 30 pesticides were measured. The pesticides were divided into five groups to
      verify the separation capability of pulse glow discharge in mobility
      spectrometry. The extraction conditions such as desorption solvent, ionic
      strength, conditions of adsorption and desorption, the amounts of multiwalled
      carbon nanotubes, and solution pH were optimized. The enrichment factors of
      pesticides were 5.4- to 48.7-fold (theoretical enrichment factor was 50-fold).
      The detection limits of pesticides were 0.01~0.77 MUg/kg. The linear range was
      0.005-0.2 mg/L for pesticide standard solutions, with determination coefficients
      from 0.9616 to 0.9999. The method was applied for the analysis of practical and
      spiked drinking water samples. All results were confirmed by high-performance
      liquid chromatography with tandem mass spectrometry. The proposed method was
      proven to be a commendably rapid screening qualitative and semiquantitative
      technique for the analysis of pesticide residues in drinking water samples on
      site. 

PMID- 27027595
TI  - Addressing mental health through sport: a review of sporting organizations'
      websites.
AB  - AIM: Mental health is a major concern among adolescents. Most mental illnesses
      have their onset during this period, and around 14% of all young people aged 12
      to 17 years experience a mental illness in a 12-month period. However, only 65%
      of these adolescents access health services to address their mental health
      problems. Approximately 70% of all Australian adolescents participate in sport,
      and this presents an opportunity for mental health promotion. METHODS: This paper
      reviewed current approaches by sporting organizations to mental health promotion,
      prevention and early intervention by searching peak body websites, as well as the
      wider Internet. RESULTS: Findings revealed many of the sport organizations
      reviewed acknowledged the importance of mental components of their sport to
      increase competitiveness, but few explicitly noted mental health problems or the
      potential of their sport to promote good mental health. Although some had
      participated in mental health promotion campaigns, there was no evaluation or
      reference to the evidence base for these campaigns. CONCLUSIONS: We describe a
      framework for integrating mental health promotion into sports organizations based
      on the MindMatters programme for schools.

PMID- 27027596
TI  - Current concepts related to hypertrophic scarring in burn injuries.
AB  - Scarring following burn injury and its accompanying aesthetic and functional
      sequelae still pose major challenges. Hypertrophic scarring (HTS) can greatly
      impact patients' quality of life related to appearance, pain, pruritus and even
      loss of function of the injured body region. The identification of molecular
      events occurring in the evolution of the burn scar has increased our knowledge;
      however, this information has not yet translated into effective treatment
      modalities. Although many of the pathophysiologic pathways that bring about
      exaggerated scarring have been identified, certain nuances in burn scar formation
      are starting to be recognized. These include the effects of neurogenic
      inflammation, mechanotransduction, and the unique interactions of burn wound
      fluid with fat tissue in the deeper dermal layers, all of which may influence
      scarring outcome. Tension on the healing scar, pruritus, and pain all induce
      signaling pathways that ultimately result in increased collagen formation and
      myofibroblast phenotypic changes. Exposure of the fat domes in the deep dermis is
      associated with increased HTS, possibly on the basis of altered interaction of
      adipose-derived stem cells and the deep burn exudate. These pathophysiologic
      patterns related to stem cell-cytokine interactions, mechanotransduction, and
      neurogenic inflammation can provide new avenues of exploration for possible
      therapeutic interventions.

PMID- 27027597
TI  - CD56(dim)CD16(high) and CD56(bright)CD16(-) cell percentages associated with
      maximum knee extensor strength and incidence of death in elderly.
AB  - Physical fitness is an indicator of systemic well-being in humans. Little is
      known about the role of physical fitness for maintaining systemic health in the
      elderly. Here, we study elderly subjects to determine the relationships between
      physical fitness and CD56 and CD16 surface NK cell markers on peripheral blood
      lymphocytes, as well as to analyze the relationship between the surface markers
      and incidence of death. We selected 253 independent elderly subjects (122 female;
      131 male) who were 79-80 years old. Subjects having a higher proportion of
      CD56(dim)CD16(high) within CD56(+)CD16(+) cells, or ration of CD56(dim)CD16(high)
      and CD56(dim)CD16(-) cells had a significant positive correlation with maximum
      bilateral knee extensor strength/weight (kg) (r = 0.425; P < 0.0001 or r = 0.323;
      P < 0.0001). In contrast, an increased proportion of CD56(bright)CD16(-) cells
      within lymphocyte significantly negatively correlated with the maximum bilateral
      knee extensor strength/weight (kg) (r = -0.290; P = 0.0004); and these subjects
      had a significantly lower mortality during the 5 years following measurement of
      death. Therefore, we found that a synergistic effect of the right and left leg
      muscle strength was associated with proportion of matured NK and NKT cells and
      induced a low proportion of CD56(bright)CD16(-) cells within lymphocyte.
      Moreover, the low proportion of CD56(bright)CD16(-) cells was associated with
      incidence of death. In conclusion, measurements of physical fitness, the
      proportion of CD56(dim)CD16(high) within CD56(+)CD16(+) cells, the ratio of
      CD56(dim)CD56(high) and CD56(dim)CD16(-) cells, and the proportion of
      CD56(bright)C16(-) cells in lymphocytes are important indicators to check elderly
      health. 

PMID- 27027598
TI  - Paramedic Checklists do not Accurately Identify Post-ictal or Hypoglycaemic
      Patients Suitable for Discharge at the Scene.
AB  - OBJECTIVES: The objective of this study was to assess the accuracy and safety of
      two pre-defined checklists to identify prehospital post-ictal or hypoglycemic
      patients who could be discharged at the scene. METHODS: A retrospective cohort
      study of lower acuity, adult patients attended by paramedics in 2013, and who
      were either post-ictal or hypoglycemic, was conducted. Two self-care pathway
      assessment checklists (one each for post-ictal and hypoglycemia) designed as
      clinical decision tools for paramedics to identify patients suitable for
      discharge at the scene were used. The intention of the checklists was to provide
      paramedics with justification to not transport a patient if all checklist
      criteria were met. Actual patient destination (emergency department [ED] or
      discharge at the scene) and subsequent events (eg, ambulance requests) were
      compared between patients who did and did not fulfill the checklists. The
      performance of the checklists against the destination determined by paramedics
      was also assessed. RESULTS: Totals of 629 post-ictal and 609 hypoglycemic
      patients were identified. Of these, 91 (14.5%) and 37 (6.1%) patients fulfilled
      the respective checklist. Among those who fulfilled the checklist, 25 (27.5%)
      post-ictal and 18 (48.6%) hypoglycemic patients were discharged at the scene, and
      21 (23.1%) and seven (18.9%) were admitted to hospital after ED assessment.
      Amongst post-ictal patients, those fulfilling the checklist had more subsequent
      ambulance requests (P=.01) and ED attendances with seizure-related conditions
      (P=.04) within three days than those who did not. Amongst hypoglycemic patients,
      there were no significant differences in subsequent events between those who did
      and did not meet the criteria. Paramedics discharged five times more hypoglycemic
      patients at the scene than the checklist predicted with no significant
      differences in the rate of subsequent events. Four deaths (0.66%) occurred within
      seven days in the hypoglycemic cohort, and none of them were attributed directly
      to hypoglycemia. CONCLUSIONS: The checklists did not accurately identify patients
      suitable for discharge at the scene within the Emergency Medical Service.
      Patients who fulfilled the post-ictal checklist made more subsequent health care
      service requests within three days than those who did not. Both checklists showed
      similar occurrence of subsequent events to paramedics' decision, but the
      hypoglycemia checklist identified fewer patients who could be discharged at the
      scene than paramedics actually discharged. Reliance on these checklists may
      increase transportations to ED and delay initiation of appropriate treatment at a
      hospital. Tohira H , Fatovich D , Williams TA , Bremner A , Arendts G , Rogers IR
      , Celenza A , Mountain D , Cameron P , Sprivulis P , Ahern T , Finn J . Paramedic
      checklists do not accurately identify post-ictal or hypoglycaemic patients
      suitable for discharge at the scene. Prehosp Disaster Med. 2016;31(3):282-293.

PMID- 27027599
TI  - Inspiring Infancy: interrelations between sensory, motor, and cognitive abilities
      during typical and atypical development.

PMID- 27027600
TI  - Neural reuse in the organization and development of the brain.
AB  - Neural reuse is the process by which neural elements originally developed for one
      purpose are put to many different subsequent uses. In this brief review I will
      outline the role of neural reuse in the development of the brain. Special
      attention will be paid to elucidating and differentiating between two different
      mechanisms of neurocognitive development: Hebbian plasticity, the importance of
      which is already well known, and a neural search mechanism that supports the
      establishment of new functional partnerships in the brain. I describe how these
      two mechanisms work in concert throughout development to produce the functional
      architecture we observe in the adult brain; outline the evidence for the
      importance of neural reuse; offer suggestions for some clinical implications of
      neural reuse; and point to future research directions. 

PMID- 27027602
TI  - Developing body representations in early life: combining somatosensation and
      vision to perceive the interface between the body and the world.
AB  - This article lays out the computational challenges involved in constructing
      multisensory representations of the body and the interface between the body and
      the external world. It then provides a review of the most pertinent empirical
      literature regarding the ontogeny of such representational abilities in early
      life, focussing especially on ability to make spatiotemporal links between bodily
      events transduced by vision and somatosensation (cutaneous touch and
      proprioception), and the ability to use multisensory bodily cues to locate
      tactile stimuli. Findings from infants, children, and blind adults point towards
      a trajectory of development in early life in which infants and children, as a
      result of sensory experience, learn new ways of combining cues concerning the
      body arising from vision and somatosensation, in order to best represent the
      layout of their limbs and sensory events occurring on their limbs in relation to
      the external environment. 

PMID- 27027601
TI  - Prenatal ischemia deteriorates white matter, brain organization, and function:
      implications for prematurity and cerebral palsy.
AB  - Cerebral palsy (CP) describes a group of neurodevelopmental disorders of posture
      and movement that are frequently associated with sensory, behavioral, and
      cognitive impairments. The clinical picture of CP has changed with improved
      neonatal care over the past few decades, resulting in higher survival rates of
      infants born very preterm. Children born preterm seem particularly vulnerable to
      perinatal hypoxia-ischemia insults at birth. Animal models of CP are crucial for
      elucidating underlying mechanisms and for development of strategies of
      neuroprotection and remediation. Most animal models of CP are based on hypoxia
      ischemia around the time of birth. In this review, we focus on alterations of
      brain organization and functions, especially sensorimotor changes, induced by
      prenatal ischemia in rodents and rabbits, and relate these alterations to
      neurodevelopmental disorders found in preterm children. We also discuss recent
      literature that addresses the relationship between neural and myelin plasticity,
      as well as possible contributions of white matter injury to the emergence of
      brain dysfunctions induced by prenatal ischemia. 

PMID- 27027603
TI  - Postural variability and sensorimotor development in infancy.
AB  - Infants develop skills through a coupling between their sensory and motor
      systems. Newborn infants must interpret sensory information and use it to modify
      movements and organize the postural control system based on the task demands.
      This paper starts with a brief review of evidence on the use of sensory
      information in the first months of life, and describes the importance of movement
      variability and postural control in infancy. This introduction is followed by a
      review of the evidence for the interactions between the sensory, motor, and
      postural control systems in typically development infants. The paper highlights
      the ability of young infants to use sensory information to modify motor behaviors
      and learn from their experiences. Last, the paper highlights evidence of atypical
      use of sensory, motor, and postural control in the first months of life in
      infants who were born preterm, with neonatal brain injury or later diagnosed with
      cerebral palsy (CP). 

PMID- 27027604
TI  - Anticipatory control and spatial cognition in locomotion and navigation through
      typical development and in cerebral palsy.
AB  - Behavioural evidence, summarized in this narrative review, supports a
      developmental model of locomotor control based on increasing neural integration
      of spatial reference frames. Two consistent adult locomotor behaviours are head
      stabilization and head anticipation: the head is stabilized to gravity and leads
      walking direction. This cephalocaudal orienting organization aligns gaze and
      vestibula with a reference frame centred on the upcoming walking direction,
      allowing anticipatory control on body kinematics, but is not fully developed
      until adolescence. Walking trajectories and those of hand movements share many
      aspects, including power laws coupling velocity to curvature, and minimized
      spatial variability. In fact, the adult brain can code trajectory geometry in an
      allocentric reference frame, irrespective of the end effector, regulating body
      kinematics thereafter. Locomotor trajectory formation, like head anticipation,
      matures in early adolescence, indicating common neurocomputational substrates.
      These late-developing control mechanisms can be distinguished from biomechanical
      problems in children with cerebral palsy (CP). Children's performance on a novel
      navigation test, the Magic Carpet, indicates that typical navigation development
      consists of the increasing integration of egocentric and allocentric reference
      frames. In CP, right-brain impairment seems to reduce navigation performance due
      to a maladaptive left-brain sequential egocentric strategy. Spatial integration
      should be considered more in rehabilitation. 

PMID- 27027605
TI  - Functional magnetic resonance connectivity studies in infants born preterm:
      suggestions of proximate and long-lasting changes in language organization.
AB  - Sophisticated neuroimaging strategies demonstrate alterations in functional
      connectivity at school age, adolescence, and young adulthood in individuals born
      preterm. Recent data suggest these alterations are present in the postnatal
      period prior to term-equivalent age in neonates born preterm. Likewise,
      functional organization increases across development, but the influence of
      preterm birth on this fundamental infrastructure is immediate and unchanging.
      This article briefly reviews the current methods of measuring functional
      connectivity throughout development in those born preterm, and the association of
      functional connectivity with language disorders. Taken together, these data
      suggest that the effects of preterm birth on the functional organization of
      language in the developing brain are both proximate and long-lasting. 

PMID- 27027607
TI  - Motor and cognitive outcome after specific early lesions of the brain - a
      systematic review.
AB  - The aim of this systematic review was to study motor and cognitive outcome in
      infants with severe early brain lesions and to evaluate effects of side of the
      lesion, sex, and social economic status on outcome. A literature search was
      performed using the databases Pubmed and Embase. Included studies involved
      infants with either cystic periventricular leukomalacia (cPVL), preterm, or term
      stroke (i.e. parenchymal lesion of the brain). Outcome was expressed as cerebral
      palsy (CP) and intellectual disability (mental retardation). Median prevalence
      rates of CP after cPVL, preterm, and term stroke were 86%, 71%, and 29%
      respectively; of intellectual disability 50%, 27%, and 33%. Most infants with
      cPVL developed bilateral CP, those with term stroke unilateral CP, whereas after
      preterm stroke bilateral and unilateral CP occurred equally often. Information on
      the effects of sex and social economic status on outcome after specific brain
      lesions was very limited. Our findings show that the risk for CP is high after
      cPVL, moderate after preterm stroke, and lowest after term stroke. The risk for
      intellectual disability after an early brain lesion is lower than that for CP.
      Predicting outcome at individual level remains difficult; new imaging techniques
      may improve predicting developmental trajectories. 

PMID- 27027606
TI  - Alterations in development of hippocampal and cortical memory mechanisms
      following very preterm birth.
AB  - Deficits in memory function have been described in children and adolescents who
      were born very preterm (VPT), which can have profound effects on their school
      achievement and everyday life. However, to date, little is known about the
      development of the neuroanatomical substrates of memory following VPT birth. Here
      we focus on episodic and working memory and highlight key recent functional and
      structural magnetic resonance imaging (MRI) studies that have advanced our
      understanding of the relationship between alterations seen in the VPT brain and
      typical neurodevelopment of networks supporting these memory functions. We
      contrast evidence from the episodic and working memory literatures and suggest
      that knowledge gained from these functional and neuroanatomical studies may point
      to specific time windows in which working memory interventions may be most
      effective. 

PMID- 27027608
TI  - Prognostic significance of neurological signs in high-risk infants - a systematic
      review.
AB  - The aim of this paper was to systematically review the literature on the
      significance of specific neurological signs in infancy, in particular in infants
      at risk for developmental problems such as cerebral palsy (CP). A literature
      search was performed using the databases PubMed, Embase, Web of Science, and
      AMED. Papers on infantile reactions ('primitive reflexes') and postural reactions
      were included if data were available allowing for calculation of sensitivity,
      specificity, or positive and negative predictive value for CP or atypical
      developmental outcome. Our search identified 23 articles on 20 different
      neurological signs. Properties of six neurological signs were reported in at
      least three different papers. The data indicated that, in early infancy, an
      absent Moro or plantar grasp response may be predictive for adverse developmental
      outcome. After early infancy, persistence of the Moro response and asymmetric
      tonic neck reflex was clinically significant. Prediction of a delayed emergence
      of the parachute reaction increases with age. Abnormal performances on the pull
      to-sit manoeuvre and vertical suspension test have predictive significance
      throughout infancy. The neurological signs reviewed have some predictive value in
      infants at risk. For most of the signs, criteria for abnormality and significance
      are age-dependent. 

PMID- 27027609
TI  - Early intervention in neurodevelopmental disorders: underlying neural mechanisms.
AB  - Neurodevelopmental disorders affect motor, cognitive, language, learning, and
      behavioural development with lifelong consequences. Early identification of
      infants at risk for neurodevelopmental disorders is a major prerequisite for
      intervention programmes. This ensures that interventions which aim to positively
      modify the natural history of these disorders can start in the first weeks or
      months of life. As indicated by recent scientific evidence, gene abnormalities or
      congenital brain lesions are not the sole determinants for the neurodevelopmental
      outcome of affected infants. In fact, environment and experience may modify brain
      development and improve the outcome in infants at risk for neurodevelopmental
      disorders. In this review, we analyse the complexity and sensitivity of the brain
      to environmental stimuli, highlighting clinical effects of early intervention,
      mainly reported so far in preterm infants, and summarizing the effects of
      enriched environment on human and animal models. Finally, we discuss some new
      approaches to early intervention, based on recent neurophysiological theories and
      new breakthroughs in biotechnologies for diagnosis and rehabilitation. 

PMID- 27027610
TI  - Rethinking preventive post-discharge intervention programmes for very preterm
      infants and their parents.
AB  - Post-discharge preventive intervention programmes with involvement of the parent
      may support the resilience and developmental outcomes of infants born very
      preterm. Randomized controlled trials of home-based family-centred intervention
      programmes in very preterm infants that aimed to improve cognitive outcome, at
      least at age two, were selected and updated on the basis of a recent systematic
      review to compare their content and effect over time to form the basis of a
      narrative review. Six programmes were included in this narrative review. Four of
      the six programmes led to improved child cognitive and/or motor development. Two
      programmes, which focused primarily on responsive parenting and development,
      demonstrated improved cognitive outcome up till 5 years after completion of the
      programme. The programmes that also focused on maternal anxiety remediation led
      to improved maternal mental well-being, along with improved child behaviour, in
      one study - even at 3 years after completion of the programme. The magnitude of
      the effects was modest. Family-centred preventive intervention programmes that
      aim at improvement of child development should be continued after discharge home
      to improve the preterm child's resilience. Programmes may be most effective when
      they support the evolvement of a responsive parent-infant relationship over time,
      as well as the parent's well-being.

PMID- 27027611
TI  - Action observation in infancy: implications for neuro-rehabilitation.
AB  - Action observation therapy has been found to be effective in improving hand motor
      function in both adults with stroke and children with unilateral cerebral palsy.
      We here propose a provocative hypothesis arguing that the same therapy might be
      effective in very early intervention in infants with unilateral or asymmetric
      brain damage, but through a different underlying mechanism. If the activation of
      motor networks induced in infancy by action observation enhances the excitability
      of the damaged sensorimotor cortex, it could also accelerate the maturation of
      the corticospinal tract and the adaptive shaping of the spinal motor circuits.
      This hypothesis should be explored carefully in prospective studies and, if
      confirmed, might support the use of action observation therapy at a much earlier
      time than experimented so far. 

PMID- 27027612
TI  - Lessons learned from studying the functional impact of adaptive seating
      interventions for children with cerebral palsy.
AB  - Little empirical evidence exists about the effectiveness of assistive technology
      interventions for children with cerebral palsy (CP) to inform clinical practice.
      This article reviews what we know about the functional impact of adaptive seating
      interventions - a common assistive technology type recommended for children with
      CP. A contemporary assistive technology outcomes framework is considered as a way
      to model the temporality and measure the effects of seating interventions and
      moderating cofactors. Three research studies are profiled to illustrate different
      research methods, measurement approaches, and follow-up periods to learn about
      adaptive seating outcomes. Recommendations for future research include the
      adoption of common measurement indicators, consideration of quality assessment
      criteria, and the use of varied methodologies to generate new knowledge about
      functional outcomes. It is suggested that the proposed strategies will lead to
      new understandings, clinical applications, and ultimately improvements in the
      everyday lives of children with CP and their families. 

PMID- 27027613
TI  - Function-Oriented Synthesis: How to Design Simplified Analogues of Antibacterial
      Nucleoside Natural Products?
AB  - It is important to pursue function-oriented synthesis (FOS), a strategy for the
      design of less structurally complex targets with comparable or superior activity
      that can be made in a practical manner, because compared to synthetic drugs, many
      biologically relevant natural products possess large and complex chemical
      structures that may restrict chemical modifications in a structure-activity
      relationship study. In this account, we describe recent efforts to simplify
      complex nucleoside natural products including caprazamycins. Considering the
      structure-activity relationship study with several truncated analogues, three
      types of simplified derivatives, namely, oxazolidine, isoxazolidine, and lactam
      fused isoxazolidine-containing uridine derivatives, were designed and efficiently
      synthesized. These simplified derivatives have exhibited promising antibacterial
      activities. A significant feature of our studies is the rational and drastic
      simplification of the molecular architecture of caprazamycins. This study
      provides a novel strategy for the development of a new type of antibacterial
      agent effective against drug-resistant bacteria.

PMID- 27027614
TI  - Diffusion weighted imaging in gynecological malignancies - present and future.
AB  - The management of gynaecological malignancies has undergone a significant change
      in recent years with our improved understanding of cancer biogenetics,
      development of new treatment regimens and enhanced screening. Due to the rapid
      blooming of newer methods and techniques in gynaecology, surgery and oncology the
      scope and the role of imaging has also widened. Functional imaging in the form of
      diffusion weighted imaging (DWI) has been recently found to be very useful in
      assessing various tumours. Its ability to identify changes in the molecular level
      has dramatically changed the diagnostic approach of radiologists which was solely
      based on morphological criteria. It can improve the diagnostic accuracy of
      conventional magnetic resonance imaging, lend a hand in assessing tumour response
      to treatment regimens and detect tumour recurrence with better spatial
      resolution, negative radiation and diagnostic accuracy compared to positron
      emission tomography scan. The ability to quantify the diffusion has also lead to
      potential prediction of tumour aggressiveness and grade which directly correlate
      with the patient prognosis and management. Hence, it has become imperative for a
      radiologist to understand the concepts of DWI and its present and evolving role.
      In this article we present a brief description of the basics of DWI followed by
      its role in evaluation of female gynaecological malignancies. 

PMID- 27027615
TI  - Taste detection ability of elderly nursing home residents.
AB  - Due to the rapid rise of aged populations throughout the world, it is essential
      to elucidate the cause of taste dysfunction, because it may reduce appetite,
      leading to inadequate dietary intake. We aimed to compare taste detection ability
      between dependently and independently living geriatric individuals of nearly the
      same age with oral status. Forty-three elderly individuals considered to be
      cognitively eligible and residing in nursing homes in Japan were enrolled (n =
      43, 82.3 +/- 8.5 years) and were compared with an independently living elderly
      group (n = 949, 79.9 +/- 0.8 years), aiming to compare taste detection ability
      between dependently and independently living elders of nearly the same age.
      Information regarding comorbidity and medication was obtained as general health
      status, and oral status including number of present teeth, denture usage and
      maximal occlusal force was also noted. In the dependently living group, 69.4%,
      14.3%, 16.3% and 8.2% of participants could detect sweet, sour, salty and bitter
      tastes, respectively, which was significantly lower than the independently living
      group for each taste (97.9%, 70.8%, 89.6% and 43.8% for sweet, sour, salty and
      bitter tastes, respectively). The multivariate logistic regression analysis
      revealed that residing in nursing homes was associated with reduced sensitivity
      for four different tastes. The diseases and the situation of dependent elders
      were more likely the cause of the decreased taste sensitivity. 

PMID- 27027616
TI  - N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced
      sympathoexcitation in human subjects.
AB  - NEW FINDINGS: What is the central question of this study? This study evaluated
      the following central question: does N-acetylcysteine (N-AC), an antioxidant that
      readily penetrates the blood-brain barrier, have the capability to reduce the
      increase in sympathetic nerve activity observed during hyperacute intermittent
      hypoxia? What is the main finding and its importance? We demonstrate that N-AC
      decreases muscle sympathetic nerve activity in response to hyperacute
      intermittent hypoxia versus placebo control. This finding suggests that
      antioxidants, such as N-AC, have therapeutic potential in obstructive sleep
      apnoea. This investigation tested the following hypotheses: that (i) N
      acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced
      sympathoexcitation, (ii) without elevating superoxide measured in peripheral
      venous blood. Twenty-eight healthy human subjects were recruited to the study.
      One hour before experimentation, each subject randomly ingested either 70 mg kg(
      1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial
      blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood
      superoxide concentration (using electron paramagnetic resonance spectroscopy; n =
      12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia
      training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with
      100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT
      compared with placebo (P < 0.02). However, N-AC did not alter superoxide
      concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT
      did not increase superoxide concentrations in the peripheral circulation as
      measured by electron paramagnetic resonance (P > 0.05). Based on these findings,
      we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily
      mediated centrally rather than peripherally, although central measurements of
      reactive oxygen species are difficult to obtain in human subjects, thus making
      this assertion difficult to verify. This investigation suggests the possibility
      of developing a pharmaceutical therapy to inhibit the sympathoexcitation
      associated with obstructive sleep apnoea.

PMID- 27027617
TI  - National Use of Safety-Net Clinics for Primary Care among Adults with Non
      Medicaid Insurance in the United States.
AB  - OBJECTIVE: To describe the prevalence, characteristics, and predictors of safety
      net use for primary care among non-Medicaid insured adults (i.e., those with
      private insurance or Medicare). METHODS: Cross-sectional analysis using the 2006
      2010 National Ambulatory Medical Care Surveys, annual probability samples of
      outpatient visits in the U.S. We estimated national prevalence of safety-net
      visits using weighted percentages to account for the complex survey design. We
      conducted bivariate and multivariate logistic regression analyses to examine
      characteristics associated with safety-net clinic use. RESULTS: More than one
      third (35.0%) of all primary care safety-net clinic visits were among adults with
      non-Medicaid primary insurance, representing 6,642,000 annual visits nationally.
      The strongest predictors of safety-net use among non-Medicaid insured adults
      were: being from a high-poverty neighborhood (AOR 9.53, 95% CI 4.65-19.53), being
      dually eligible for Medicare and Medicaid (AOR 2.13, 95% CI 1.38-3.30), and being
      black (AOR 1.97, 95% CI 1.06-3.66) or Hispanic (AOR 2.28, 95% CI 1.32-3.93).
      Compared to non-safety-net users, non-Medicaid insured adults who used safety-net
      clinics had a higher prevalence of diabetes (23.5% vs. 15.0%, p<0.001),
      hypertension (49.4% vs. 36.0%, p<0.001), multimorbidity (>=2 chronic conditions;
      53.5% vs. 40.9%, p<0.001) and polypharmacy (>=4 medications; 48.8% vs. 34.0%,
      p<0.001). Nearly one-third (28.9%) of Medicare beneficiaries in the safety-net
      were dual eligibles, compared to only 6.8% of Medicare beneficiaries in non
      safety-net clinics (p<0.001). CONCLUSIONS: Safety net clinics are important
      primary care delivery sites for non-Medicaid insured minority and low-income
      populations with a high burden of chronic illness. The critical role of safety
      net clinics in care delivery is likely to persist despite expanded insurance
      coverage under the Affordable Care Act.

PMID- 27027619
TI  - Insights into the Ecology and Evolution of Polyploid Plants through Network
      Analysis.
AB  - Polyploidy is a widespread phenomenon throughout eukaryotes, with important
      ecological and evolutionary consequences. Although genes operate as components of
      complex pathways and networks, polyploid changes in genes and gene expression
      have typically been evaluated as either individual genes or as a part of broad
      scale analyses. Network analysis has been fruitful in associating genomic and
      other 'omic'-based changes with phenotype for many systems. In polyploid species,
      network analysis has the potential not only to facilitate a better understanding
      of the complex 'omic' underpinnings of phenotypic and ecological traits common to
      polyploidy, but also to provide novel insight into the interaction among
      duplicated genes and genomes. This adds perspective to the global patterns of
      expression (and other 'omic') change that accompany polyploidy and to the
      patterns of recruitment and/or loss of genes following polyploidization. While
      network analysis in polyploid species faces challenges common to other analyses
      of duplicated genomes, present technologies combined with thoughtful experimental
      design provide a powerful system to explore polyploid evolution. Here, we
      demonstrate the utility and potential of network analysis to questions pertaining
      to polyploidy with an example involving evolution of the transgressively superior
      cotton fibres found in polyploid Gossypium hirsutum. By combining network
      analysis with prior knowledge, we provide further insights into the role of
      profilins in fibre domestication and exemplify the potential for network analysis
      in polyploid species. 

PMID- 27027618
TI  - Streptococcus pyogenes Pneumonia in Adults: Clinical Presentation and Molecular
      Characterization of Isolates 2006-2015.
AB  - INTRODUCTION: In the preantibiotic era Streptococcus pyogenes was a common cause
      of severe pneumonia but currently, except for postinfluenza complications, it is
      not considered a common cause of community-acquired pneumonia in adults. AIM AND
      MATERIAL AND METHODS: This study aimed to identify current clinical episodes of
      S. pyogenes pneumonia, its relationship with influenza virus circulation and the
      genotypes of the involved isolates during a decade in a Southern European region
      (Gipuzkoa, northern Spain). Molecular analysis of isolates included emm,
      multilocus-sequence typing, and superantigen profile determination. RESULTS:
      Forty episodes were detected (annual incidence 1.1 x 100,000 inhabitants, range
      0.29-2.29). Thirty-seven episodes were community-acquired, 21 involved an
      invasive infection and 10 developed STSS. The associated mortality rate was 20%,
      with half of the patients dying within 24 hours after admission. Influenza
      coinfection was confirmed in four patients and suspected in another. The 52.5% of
      episodes occurred outside the influenza seasonal epidemic. The 67.5% of affected
      persons were elderly individuals and adults with severe comorbidities, although
      13 patients had no comorbidities, 2 of them had a fatal outcome. Eleven clones
      were identified, the most prevalent being emm1/ST28 (43.6%) causing the most
      severe cases. CONCLUSIONS: S. pyogenes pneumonia had a continuous presence
      frequently unrelated to influenza infection, being rapidly fatal even in
      previously healthy individuals.

PMID- 27027620
TI  - Prospective Clinical Comparison of Patient Outcomes Following Implantation of
      Trifocal or Bifocal Intraocular Lenses.
AB  - PURPOSE: To compare the visual results and patient satisfaction after bilateral
      implantation between a bifocal and a trifocal intraocular lens (IOL). METHODS:
      This study is a prospective, randomized, controlled study involving bilateral
      implantation of one of two multifocal IOLs. Patients were assessed for
      uncorrected and distance-corrected near (33 cm), intermediate (66 cm), and
      distance visual acuity. Distance contrast sensitivity under photopic (85 cd/m2)
      conditions with and without glare was also measured. Using a subjective
      questionnaire, patient satisfaction, spectacle independence, and the perception
      of glare and halo phenomena were evaluated at the final follow-up; a defocus
      curve analysis was conducted. RESULTS: Fifteen patients (30 eyes) were implanted
      with the FineVision IOL (PhysIOL, Liege, Belgium) and 12 patients (24 eyes)
      received the Tecnis ZMB00 IOL (Abbott Medical Optics, Santa Ana, CA). The average
      follow-up was 6 months. The mean binocular uncorrected visual acuity was 0.02 +/-
      0.04 logMAR in the FineVision group and 0.04 +/- 0.05 logMAR in the Tecnis group
      and the mean binocular uncorrected near visual acuity was 0.01 +/- 0.00 logMAR in
      both groups. In the intermediate range of the defocus curve, there was a
      statistically significant difference between the two IOLs (P < .05). Contrast
      sensitivity was within normal limits under photopic conditions in both groups.
      CONCLUSIONS: Both the Tecnis and FineVision IOLs provide a satisfactory range of
      vision, including a high level of uncorrected distance, intermediate, and near
      acuity and improved contrast sensitivity under photopic conditions.

PMID- 27027621
TI  - Stability of Keratometric Astigmatism After Non-penetrating Femtosecond Laser
      Intrastromal Astigmatic Keratotomy Performed During Laser Cataract Surgery.
AB  - PURPOSE: To investigate the stability of keratometric astigmatism after
      femtosecond laser intrastromal astigmatic keratotomy (ISAK) performed during
      laser cataract surgery. METHODS: In this prospective comparative case series,
      data were collected from patients during follow-up 1 and 6 months after laser
      assisted cataract surgery. Corneal keratometry was measured preoperatively and
      postoperatively by Topcon KR8100PA topographer-autorefractor (Topcon Corporation,
      Tokyo, Japan). Astigmatic analyses were performed by Alpins' method to calculate
      surgically induced astigmatism (SIA). All operations were performed by a single
      surgeon. RESULTS: Data were available on 263 eyes, of which 87 had undergone ISAK
      during cataract surgery for astigmatism management (cases) and 176 had cataract
      surgery without ISAK (controls). For ISAK cases, comparing the magnitudes of the
      individual SIA vectors at 1 and 6 months postoperatively showed a 0.09 diopters
      cylinder (DC) regression (P = .009). Calculating the change in SIA between 1 and
      6 months considering both magnitude and angular direction, the mean regression
      vector was 0.08 DC @ 94 degrees . For controls (without ISAK), comparing the
      magnitudes of the individual SIA vectors at 1 and 6 months postoperatively showed
      a 0.11 DC regression (P < .001). Calculating the change in SIA between 1 and 6
      months considering magnitude and angular direction, the mean vector was 0.14 DC @
      88 degrees . There was no significant difference in SIA regression magnitudes
      between cases and controls. CONCLUSIONS: For both cases with and without ISAK,
      there were small but statistically significant regressions in SIA between 1 and 6
      months postoperatively. These values were low and appear to be of little clinical
      significance.

PMID- 27027622
TI  - Effect of Limbal Relaxing Incisions on Corneal Aberrations.
AB  - PURPOSE: To study the effect of limbal relaxing incisions on corneal aberrations
      after phacoemulsification with aspheric intraocular lens (IOL) implantation.
      METHODS: Forty-five eyes underwent microincision cataract surgery with on-axis
      phacoemulsification incision. These eyes were divided into two groups: limbal
      relaxing incision group (23 eyes) and control group (22 eyes). In the limbal
      relaxing incision group, a single limbal relaxing incision was performed on the
      steepest meridian of corneal topography and the degrees of arc were determined
      using the DONO-Donnenfeld nomogram. The eyes in the control group were operated
      on by microincision cataract surgery without limbal relaxing incision. Corneal
      topography and wavefront analysis over 6-mm pupil size were performed
      preoperatively and 1 month postoperatively in both groups. Target induced
      astigmatism vector, surgically induced astigmatism vector, difference vector,
      magnitude of error, flattening effect, and torque were analyzed using the Alpins
      vectorial method. RESULTS: The limbal relaxing incision group showed significant
      reduction in topographic astigmatism by 51.87% of preoperative topographical
      astigmatism (P < .0001). The mean surgically induced astigmatism of limbal
      relaxing incision was 1.29 +/- 0.71 diopters (D), which was close to the mean
      target induced astigmatism (1.33 +/- 0.20 D), whereas the control group did not
      show a significant change in topographic astigmatism (0.17 +/- 0.11 D; P = .73).
      Higher order aberrations of the cornea did not show significant change in either
      group except quatrefoil aberration, which significantly increased in the limbal
      relaxing incision group but not in the control group, with no significant
      difference between the two groups regarding corneal aberrations. CONCLUSIONS:
      Limbal relaxing incision is an effective method in reducing corneal astigmatism
      with neutral effect on corneal aberrations.

PMID- 27027623
TI  - Agreement Between Predicted and Measured Ablation Depth After Femtosecond Laser
      Assisted LASIK for Myopia.
AB  - PURPOSE: To investigate agreement between the predicted ablation depth calculated
      by the EX500 excimer laser (Wavelight Laser Technologie AG, Erlangen, Germany)
      and the measured ablation depth in eyes that have undergone femtosecond laser
      assisted LASIK (FS-LASIK) for myopia. METHODS: Corneal thickness was measured
      with a rotating Scheimpflug camera preoperatively and 3 months postoperatively
      and the difference between these values was defined as the measured ablation
      depth. The difference between the predicted and the measured ablation depth was
      defined as the difference in ablation depth (DeltaAD). RESULTS: In 85 eyes of 85
      patients, no statistically significant difference was detected between the mean
      predicted ablation depth (66.33 +/- 24.15 um) and the measured ablation depth at
      the thinnest corneal location (67.04 +/- 30.94 um), the corneal apex (67.52 +/-
      31.22 um), or the pupil center (67.73 +/- 31.48 um). Bland-Altman plots revealed
      moderate agreement for measurements at the thinnest point (95% limits of
      agreement [LoA]: -25.13 to 23.70 um), corneal apex (95% LoA: -24.70 to 22.33 um),
      and pupil center (95% LoA: -25.30 to 22.51 um), with a proportional bias between
      the average ablation depth and DeltaAD. The predicted ablation depth was
      overestimated in eyes with lower correction and underestimated in eyes with
      higher correction. CONCLUSIONS: Moderate agreement between the predicted and
      measured ablation depth warrants caution when planning myopic FS-LASIK and
      calculating the residual bed thickness and percent tissue altered. When higher
      amounts of correction are planned, the laser software may underestimate the
      predicted ablation depth.

PMID- 27027624
TI  - Transepithelial Photorefractive Keratectomy for Hyperopia: A 12-Month Bicentral
      Study.
AB  - PURPOSE: To investigate the safety, efficacy, and stability of transepithelial
      photorefractive keratectomy (PRK) for hyperopia. METHODS: This interventional
      case series study at two sites included 55 eyes (31 patients) with hyperopia
      (0.50 to 6.00 diopters [D]), with or without astigmatism (0.00 to -3.00 D), that
      underwent one-step transepithelial PRK with a Amaris 500-Hz excimer laser
      (SCHWIND eye-tech-solutions, Kleinostheim, Germany). A 12-month follow-up was
      conducted. Preoperative and successive postoperative visual acuity, manifest
      refraction, haze, and other complication data were analyzed. RESULTS: The
      preoperative mean spherical equivalent of 2.56 +/- 1.90 D improved to emmetropia
      (-0.08 +/- 0.14 D) by 6 months, with subsequent slight mean regression of 0.024 D
      (range: -0.75 to 0.50) until month 12. Of the treated eyes, 75% and 76.2% were
      within the target refraction of +/-0.50 D at 6 and 12 months postoperatively,
      respectively. The final mean cylindric refraction was comparable to the
      preoperative value (-0.94 +/- 0.12 to -0.71 +/- 0.12 D, P = .17); however, it was
      induced in 23% of eyes. The preoperative mean uncorrected distance visual acuity
      logMAR of 0.54 +/- 0.05 significantly improved to 0.15 +/- 0.03 by month 12 (P <
      .0001), and 64.2% of the treated eyes gained an uncorrected distance visual
      acuity of 20/25 or better. Ten eyes (23.8%) lost one line of preoperative
      corrected distance visual acuity (CDVA). No eye lost two or more lines of
      preoperative CDVA. Four eyes with a 3+ degree of haze were observed by the final
      visit. No other notable complications occurred. The low hyperopic eyes exhibited
      better overall results compared to the moderate hyperopic group. CONCLUSIONS: One
      step transepithelial PRK with the Amaris 500-Hz excimer laser provided reasonable
      outcomes for the correction of hyperopia with or without mild to moderate
      astigmatism.

PMID- 27027625
TI  - Corneal Power Measurement With the Dual Scheimpflug-Placido Topographer After
      Myopic Excimer Laser Surgery.
AB  - PURPOSE: To evaluate the ability of the Sirius Scheimpflug-Placido Topographer
      (Costruzione Strumenti Oftalmici, Florence, Italy) in predicting corneal power in
      eyes with previous myopic corneal refractive surgery. METHODS: The following
      corneal refractive power measurements were obtained with Sirius in 38 eyes with
      prior myopic excimer laser surgery: simulated keratometry (SimK), true net power
      based on the Gaussian optical formula (TNP), and the mean pupil power (MPP)
      calculated by ray tracing within the diameter of the entrance pupil range from
      2.5 to 6 mm. These values, along with the corresponding keratometric value, which
      was based on the equation that converted the MPP within 4.5-mm entrance pupil
      diameter to a keratometric reading in 75 myopic eyes, were compared using the
      clinical history method. RESULTS: SimK significantly overestimated corneal power
      by 0.67 +/- 0.52 diopters (D), whereas TNP significantly underestimated corneal
      power by -1.05 +/- 0.48 D. The only measurements that showed no statistically
      significant difference by the clinical history method were the 5 mm MPP, 5.5 mm
      MPP, and KMPP4.5POST, and the 95% limits of agreement (LOA) were -1.10 to 0.62, 
      0.91 to 0.89, and -0.67 to 1.05 D, respectively. CONCLUSIONS: The Sirius
      Scheimpflug-Placido Topographer is an alternative method of measuring corneal
      power in eyes with previous corneal refractive surgery for myopia when
      preoperative data are not available. The best options seem to be the 5 mm MPP,
      5.5 mm MPP, and the keratometric reading calculated from the regression formula.

PMID- 27027626
TI  - Repeatability of Keratometry Measurements Obtained With Three Topographers in
      Keratoconic and Normal Corneas.
AB  - PURPOSE: To assess the repeatability of the corneal topography functions of
      Orbscan II (Bausch & Lomb, Rochester, NY), OPD-Scan III (Nidek, Gamagori, Japan),
      and iTrace (Tracey Technologies, Houston, TX) in keratoconic eyes and in a
      control group of normal patients. METHODS: In this prospective cohort study,
      patients were recruited between November 2011 and May 2012. Measurements were
      performed with a combined Placido-scanning slit system (Orbscan II) and two
      combined Placido-aberrometer systems (OPD-Scan III and iTrace). Repeatability
      limit and intraclass correlation coefficients (ICCs) of keratometric readings
      were calculated. RESULTS: Fifty-nine keratoconic eyes of 34 patients and 54
      normal eyes of 27 patients were included. Three groups were evaluated: all stage
      I-IV keratoconic eyes (59 eyes), a subgroup consisting of stage I-II keratoconic
      eyes (41 eyes), and normal eyes (54 eyes). For almost all parameters studied, the
      repeatability limit was higher in the two groups of keratoconic eyes compared to
      normal eyes with all three topographers, indicating lower repeatability. For the
      maximum keratometry measurement, repeatability limit was 1.73, 1.49, and 1.41
      diopters (D) in the stage I-IV keratoconic eyes group, 1.11, 1.02, and 0.98 D in
      the stage I-II keratoconic eyes group, and 0.61, 0.37, and 1.02 D in the normal
      eyes group with Orbscan II, OPD-Scan III, and iTrace, respectively. CONCLUSIONS:
      Topographies performed in keratoconic eyes are less repeatable than those
      performed in normal eyes. Threshold values of keratometric changes used to
      ascertain keratoconus progression should be carefully considered. Caution should
      be taken when interpreting the topographies of such patients. The higher
      variability should be taken into account before performing any treatment.

PMID- 27027627
TI  - Analysis of the Optical Quality of Spherical and Aspheric Intraocular Lenses in
      Simulated Nanophthalmic Eyes.
AB  - PURPOSE: To analyze the optical performance of different implant strategies in
      simulated nanophthalmic eyes. METHODS: An optical design software was used.
      Analysis included eye models that required 30.00, 45.00, and 60.00 diopters (D)
      intraocular lenses (IOLs) to achieve emmetropia. Spherical and aspheric IOLs were
      designed. They were tested either with a single implant setting S or by splitting
      the power into two lenses. Setting P1 had an even split of the power between the
      lenses and setting P2 had an uneven power split with one-third of the power in
      the anterior lens and two-thirds in the posterior IOL. The area under the
      modulation transfer function (MTF) curve was calculated and spherical aberration
      was recorded in each setting. RESULTS: Setting S had the worst optical
      performance in the spherical group and the best performance in the aspheric
      group. A statistically significant difference was found between setting S and the
      piggyback options (settings P1 and P2) in all analyzed variables for the
      spherical and aspheric groups for the 45.00 and 60.00 D IOL requirement. No
      statistically significant difference was found between the piggyback settings.
      CONCLUSIONS: Single aspheric IOLs had better optical performance than
      piggybacking lower-power aspheric IOLs. In the spherical lenses group, the
      results were the opposite, with the piggyback options having higher optical
      quality than the single IOL. MTF shows that single aspheric lenses provide the
      highest contrast sensitivity among all of the analyzed settings.

PMID- 27027628
TI  - Three-dimensional Printing of Optical Lenses and Ophthalmic Surgery: Challenges
      and Perspectives.
AB  - PURPOSE: To determine whether the historical Ridley lens could be reproduced with
      current three-dimensional lens printing technology. METHODS: A reproduction of
      the Ridley lens was printed using the Printoptical Technology (LUXeXceL Group BV,
      Kruiningen, Netherlands). Photographs and electron microscopy images were taken.
      Dimensions, weight, anterior and posterior surface radius of curvature, optical
      transmission, back optical power, and surface analysis using interferometry were
      obtained. RESULTS: The printed lens was 8.10 +/- 0.01 mm in diameter, 2.50 +/-
      0.01 mm thick, and weighed 117 mg. The anterior radius of curvature was 14.63 +/-
      0.69 mm and the posterior radius of curvature was 10.88 +/- 0.22 mm. The back
      focal length in air was 14.1 +/- 0.4 mm. An average 75% transmission in the
      visible spectrum (400 to 700 nm) was achieved. Surface analysis showed
      significant surface roughness. CONCLUSIONS: The printed reproduction of the
      Ridley lens was far from current clinical standards, but had the properties of a
      biconvex lens.

PMID- 27027629
TI  - Stromal Demarcation Line in Pulsed Versus Continuous Light Accelerated Corneal
      Cross-linking for Keratoconus.
AB  - PURPOSE: To compare the stromal demarcation line depth in pulsed versus
      continuous corneal cross-linking (CXL) for keratoconus. METHODS: Seventy eyes
      underwent epithelium-off cross-linking, with 0.1% riboflavin applied during 10
      minutes prior to ultraviolet irradiation at 30 mW/cm2. Thirty-six eyes received
      pulsed irradiation (1 second on, 1 second off) for 8 minutes and 34 eyes
      underwent continuous irradiation for 4 minutes. Total fluence was 7.2 J/cm2 for
      both groups. Patients were evaluated at 3 months after the procedure. RESULTS: A
      significantly deeper stromal demarcation line was observed in the pulsed group
      compared to the continuous group (201.11 +/- 27.76 vs. 159.88 +/- 20.86 um; P <
      .001). CONCLUSIONS: The pulsed corneal cross-linking protocol induced a
      significantly deeper stromal demarcation line when compared to the 4 minutes of
      highly accelerated continuous CXL protocol. Neither CXL protocol induced a
      shallower demarcation line comparable to less accelerated CXL protocols
      previously reported.

PMID- 27027630
TI  - Optical Quality of Three Multifocal Lenses.

PMID- 27027631
TI  - Laboratory-Measured MTF of IOLs and Clinical Performance.

PMID- 27027632
TI  - Old Lineage on an Old Island: Pixibinthus, a New Cricket Genus Endemic to New
      Caledonia Shed Light on Gryllid Diversification in a Hotspot of Biodiversity.
AB  - Few studies have focused on the early colonization of New Caledonia by insects,
      after the re-emergence of the main island, 37 Myr ago. Here we investigate the
      mode and tempo of evolution of a new endemic cricket genus, Pixibinthus, recently
      discovered in southern New Caledonia. First we formally describe this new
      monotypic genus found exclusively in the open shrubby vegetation on metalliferous
      soils, named 'maquis minier', unique to New Caledonia. We then reconstruct a
      dated molecular phylogeny based on five mitochondrial and four nuclear loci in
      order to establish relationships of Pixibinthus within Eneopterinae crickets.
      Pixibinthus is recovered as the sister clade of the endemic genus Agnotecous,
      mostly rainforest-dwellers. Dating results show that the island colonization by
      their common ancestor occurred around 34.7 Myr, shortly after New Caledonia re
      emergence. Pixibinthus and Agnotecous are then one of the oldest insect lineages
      documented so far for New Caledonia. This discovery highlights for the first time
      two clear-cut ecological specializations between sister clades, as Agnotecous is
      mainly found in rainforests with 19 species, whereas Pixibinthus is found in open
      habitats with a single documented species. The preference of Pixibinthus for open
      habitats and of Agnotecous for forest habitats nicely fits an acoustic
      specialization, either explained by differences in body size or in acoustic
      properties of their respective habitats. We hypothesize that landscape dynamics,
      linked to major past climatic events and recent change in fire regimes are
      possible causes for both present-day low diversity and rarity in genus
      Pixibinthus. The unique evolutionary history of this old New Caledonian lineage
      stresses the importance to increase our knowledge on the faunal biodiversity of
      'maquis minier', in order to better understand the origin and past dynamics of
      New Caledonian biota.

PMID- 27027633
TI  - Cost-Effectiveness of Antivenoms for Snakebite Envenoming in 16 Countries in West
      Africa.
AB  - BACKGROUND: Snakebite poisoning is a significant medical problem in agricultural
      societies in Sub Saharan Africa. Antivenom (AV) is the standard treatment, and we
      assessed the cost-effectiveness of making it available in 16 countries in West
      Africa. METHODS: We determined the cost-effectiveness of AV based on a decision
      tree model from a public payer perspective. Specific AVs included in the model
      were Antivipmyn, FAV Afrique, EchiTab-G and EchiTab-Plus. We derived inputs from
      the literature which included: type of snakes causing bites (carpet viper (Echis
      species)/non-carpet viper), AV effectiveness against death, mortality without AV,
      probability of Early Adverse Reactions (EAR), likelihood of death from EAR,
      average age at envenomation in years, anticipated remaining life span and
      likelihood of amputation. Costs incurred by the victims include: costs of
      confirming and evaluating envenomation, AV acquisition, routine care, AV
      transportation logistics, hospital admission and related transportation costs,
      management of AV EAR compared to the alternative of free snakebite care with
      ineffective or no AV. Incremental Cost Effectiveness Ratios (ICERs) were assessed
      as the cost per death averted and the cost per Disability-Adjusted-Life-Years
      (DALY) averted. Probabilistic Sensitivity Analyses (PSA) using Monte Carlo
      simulations were used to obtain 95% Confidence Intervals of ICERs. RESULTS: The
      cost/death averted for the 16 countries of interest ranged from $1,997 in Guinea
      Bissau to $6,205 for Liberia and Sierra Leone. The cost/DALY averted ranged from
      $83 (95% Confidence Interval: $36-$240) for Benin Republic to $281 ($159-457) for
      Sierra-Leone. In all cases, the base-case cost/DALY averted estimate fell below
      the commonly accepted threshold of one time per capita GDP, suggesting that AV is
      highly cost-effective for the treatment of snakebite in all 16 WA countries. The
      findings were consistent even with variations of inputs in 1-way sensitivity
      analyses. In addition, the PSA showed that in the majority of iterations ranging
      from 97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali, Nigeria and
      Senegal, our model results yielded an ICER that fell below the threshold of one
      time per capita GDP, thus, indicating a high degree of confidence in our results.
      CONCLUSIONS: Therapy for SBE with AV in countries of WA is highly cost-effective
      at commonly accepted thresholds. Broadening access to effective AVs in rural
      communities in West Africa is a priority.

PMID- 27027635
TI  - Case of facial pyoderma gangrenosum.

PMID- 27027634
TI  - Pharmacokinetic comparison of oral tablet and suspension formulations of
      grapiprant, a novel therapeutic for the pain and inflammation of osteoarthritis
      in dogs.
AB  - A new anti-inflammatory drug for pain (grapiprant) was recently shown to have
      minimal side effects following chronic (9-month) daily oral dose of 6 or 50 mg/kg
      suspension. The current study compares the pharmacokinetics of the formulation
      used in the chronic safety study to those of the tablet formulation that will be
      marketed upon FDA approval. Sixteen Beagle dogs were randomized to receive single
      doses of either 6 or 50 mg/kg grapiprant as both suspension and table
      formulations within a cross-over design with a 15-day washout. Clinical
      observations were vomiting in one high-dose suspension dog and loose stools in
      two dogs, one in each 6 mg/kg formulation group. For both formulations,
      grapiprant reached a maximum concentration within two hours. The tablet
      formulation had better bioavailability, with AUClast values 34% higher at 6 mg/kg
      and 64% higher at 50 mg/kg compared to the suspension. Results on Day 0 were
      similar to those reported on Day 15, suggesting little to no accumulation. Using
      conversion factors of 1.34 and 1.64, these findings suggest that the 6 and 50
      mg/kg suspension doses are equivalent to 4.5 and 30 mg/kg tableted doses,
      respectively. Combining these findings with the 9-month safety study demonstrates
      that safety was evaluated at doses approximately 15-fold above the demonstrated
      therapeutic dose of 2 mg/kg and 10-fold over the 'safety dose', defined as the
      maximum dose a dog of any body weight could receive when dosed at 2 mg/kg with
      whole or half-tablets.

PMID- 27027636
TI  - Sodium signaling and astrocyte energy metabolism.
AB  - The Na(+) gradient across the plasma membrane is constantly exploited by
      astrocytes as a secondary energy source to regulate the intracellular and
      extracellular milieu, and discard waste products. One of the most prominent roles
      of astrocytes in the brain is the Na(+) -dependent clearance of glutamate
      released by neurons during synaptic transmission. The intracellular Na(+) load
      collectively generated by these processes converges at the Na,K-ATPase pump,
      responsible for Na(+) extrusion from the cell, which is achieved at the expense
      of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes
      to increase the local availability of metabolic substrates in response to
      neuronal activity. This review presents basic principles linking the
      intracellular handling of Na(+) following activity-related transmembrane fluxes
      in astrocytes and the energy metabolic pathways involved. We propose a role of
      Na(+) as an energy currency and as a mediator of metabolic signals in the context
      of neuron-glia interactions. We further discuss the possible impact of the
      astrocytic syncytium for the distribution and coordination of the metabolic
      response, and the compartmentation of these processes in cellular microdomains
      and subcellular organelles. Finally, we illustrate future avenues of
      investigation into signaling mechanisms aimed at bridging the gap between Na(+)
      and the metabolic machinery. GLIA 2016;64:1667-1676.

PMID- 27027637
TI  - Parenting Practices at 24 to 47 Months and IQ at Age 8: Effect-Measure
      Modification by Infant Temperament.
AB  - Cognitive development might be influenced by parenting practices and child
      temperament. We examined whether the associations between parental warmth,
      control and intelligence quotient (IQ) may be heightened among children in
      difficult temperament. Participants were from the Avon Longitudinal Study of
      Parents and Children (n = 7,044). Temperament at 6 months was measured using the
      Revised Infant Temperament Questionnaire and classified into 'easy' and
      'difficult'. Parental warmth and control was measured at 24 to 47 months and both
      were classified into 2 groups using latent class analyses. IQ was measured at 8
      years using the Wechsler Intelligence Scale for Children and dichotomized (<85
      and >=85) for analyzing effect-measure modification by temperament. Linear
      regression adjusted for multiple confounders and temperament showed lower
      parental warmth was weakly associated with lower IQ score [beta = -0.52 (95% CI
      1.26, 0.21)], and higher parental control was associated with lower IQ score
      [beta = -2.21 (-2.95, -1.48)]. Stratification by temperament showed no increased
      risk of having low IQ in temperamentally difficult children [risk ratio (RR) =
      0.97 95% CI 0.65, 1.45)] but an increased risk among temperamentally easy
      children (RR = 1.12 95% CI 0.95, 1.32) when parental warmth was low. There was
      also no increased risk of having low IQ in temperamentally difficult children (RR
      = 1.02 95% CI 0.69, 1.53) but there was an increased risk among temperamentally
      easy children (RR = 1.30 95% CI 1.11, 1.53) when parental control was high. For
      both parental warmth and control, there was some evidence of negative effect
      measure modification by temperament on the risk-difference scale and the risk
      ratio scale. It may be more appropriate to provide parenting interventions as a
      universal program rather than targeting children with difficult temperament. 

PMID- 27027638
TI  - Biomechanical potential of the temporal muscle in brachyfacial and dolichofacial
      subjects: a study on dry mandibles.
AB  - OBJECTIVES: To measure the lengths of the force and resistance arms, in order to
      calculate the mechanical advantage and muscular work of the human temporalis
      muscle (TM) in brachyfacial (BR) and dolichofacial (DO) subjects. SETTING AND
      SAMPLE POPULATION: Mandibles from 49 subjects of both genders (BR n = 9; DO n =
      40) from the collection of the Laboratory of Human Anatomy at Universidade de
      Santa Cruz do Sul, Rio Grande do Sul, Brazil, were analyzed. MATERIAL AND
      METHODS: The distance between the condylar process and the coronoid process
      (insertion site of the TM) represented the length of the force arm (LFA ) of the
      TM. The distance between the condylar process and the mental protuberance
      represented the length of the resistance arm (LRA ). Thus, the mechanical
      advantage of the TM was obtained using the following ratio: LFA /LRA , while the
      muscular work (LRA /LFA ) of the TM was obtained using the inverse of this ratio.
      RESULTS: When compared with the DO, the parameters of the BR are significantly
      greater, as shown by the LFA (6.0%) and mechanical advantage (8.2%; p = 0.0078).
      By contrast, our results show that in the DO, the LRA was 2.4% longer and the
      muscular work was 10.4% greater (p = 0.0087). CONCLUSION: The mechanical
      advantage of the TM in BR subjects is significantly greater than in DO subjects.
      Moreover, this greater mechanical advantage may explain, at least in part, the
      higher incidence of temporomandibular dysfunctions in BR subjects.

PMID- 27027639
TI  - Radical and Atom Transfer Halogenation (RATH): A Facile Route for Chemical and
      Polymer Functionalization.
AB  - This work demonstrates a new halogenation reaction through sequential radical and
      halogen transfer reactions, named as "radical and atom transfer halogenation"
      (RATH). Both benzoxazine compounds and poly(2,6-dimethyl-1,4-phenylene oxide)
      have been demonstrated as active species for RATH. Consequently, the halogenated
      compound becomes an active initiator of atom transfer radical polymerization.
      Combination of RATH and sequential ATRP provides an convenient and effective
      approach to prepare reactive and crosslinkable polymers. The RATH reaction opens
      a new window both to chemical synthesis and molecular design and preparation of
      polymeric materials. 

PMID- 27027640
TI  - Dilatable pulmonary artery band: Safety and efficacy of balloon dilatation.
AB  - OBJECTIVES: Review early and midterm results of dilatable pulmonary artery band
      (PAB). BACKGROUND: PAB is performed in various conditions: as a transient stage
      before ventricular septal defect (VSD) closure, as a palliative procedure for
      multiple VSD or to prepare the left ventricle (LV) before switch or double switch
      operations in transposition of the great artery (TGA) or congenitally corrected
      transposition of great arteries (CCTGA). METHODS: All children with dilatation of
      PAB were reviewed. Reason for PAB and for cardiac catheterization, hemodynamics,
      and outcomes were analyzed. RESULTS: Between 2002 and 2014, 28 patients were
      identified. Reason for interventional dilatation of the PAB was supra systemic
      right ventricular (RV) pressure in four patients, aortic recoarctation in one
      patient, cyanosis in seven patients, RV failure in one patient, suprasystemic LV
      pressure in two CCTGA patients and spontaneous closure of VSD in other patients.
      All patients underwent successful balloon dilatation using high (n = 21) or low
      pressure balloons with a mean diameter of 12 mm. 23 Patients had no further
      interventions. Five patients had reintervention: one needed two dilatations of
      PAB and four had surgery (one double switch, one vicious pulmonary artery (PA)
      band removal, one in a context of severe RV dysfunction with tricuspid
      regurgitation, and one for VSD closure). One patient died of RV failure following
      surgery. CONCLUSION: Balloon dilatation of dilatable PAB carries good results
      with achievement of hemodynamic aim in most of the cases and definitive treatment
      in the majority of patients. Careful and sequential dilatation with shunt
      measurement is mandatory in patients with significantly residual VSD. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27027641
TI  - A longitudinal study of the cost of food in Victoria influenced by geography and
      nutritional quality.
AB  - OBJECTIVE: To monitor the cost and affordability of a nutritious diet and to
      assess the influence of distance from the capital city and socioeconomic status
      on the cost of nutritious food in Victoria. METHODS: Twenty-six of Victoria's 79
      local government areas (33%) were randomly chosen for inclusion in the study. A
      random sample of stores was selected for inclusion from each local government
      area. The cost of the 44 'healthy' and 10 'discretionary' food and drinks in the
      healthy food basket for a family of four for a fortnight was collected during the
      winter and summer of 2012, 2013 and 2014. RESULTS: The mean cost of the basket
      increased from $424.06 +/- 38.22 in winter 2012 to $451.19 +/- 33.83 in summer
      2014 (p<0.001), representing about 31% of government benefit household income.
      Fruit and vegetables prices were the most varied over time. Distance of the store
      from state capital city centre predicted difference in food cost. CONCLUSIONS:
      These findings show that a healthy diet may be unaffordable for some Victorians.
      IMPLICATIONS: The cost of food is a key factor influencing intake. Public health
      strategies may need to consider strategies to make healthy food more affordable
      for some.

PMID- 27027642
TI  - Dissecting heterogeneity in paediatric Type 1 diabetes: association of TCF7L2
      rs7903146 TT and low-risk human leukocyte antigen (HLA) genotypes.
AB  - AIMS: To test the hypothesis that non-obese individuals with childhood-onset Type
      1 diabetes and the rs7903146 TT genotype would be less likely to have high-risk
      human leukocyte antigen (HLA) genotypes and alleles. METHODS: We studied a cohort
      of 105 non-obese participants in the T1D Exchange Biobank Residual Insulin Study
      who had childhood-onset Type 1 diabetes [mean (sd) age at onset and recruitment,
      respectively, 9.9 (4.15) and 14.4 (4.13) years; 84.8% non-Hispanic white]. We
      analysed islet autoantibodies (glutamic acid decarboxylase 65, islet cell
      autoantigen 512/islet antigen-2 and zinc transporter 8), non-fasting random C
      peptide levels, HLA type and TCF7L2 single nucleotide polymorphism rs7903146 in
      this cohort. RESULTS: None of the 13 individuals with the rs7903146 TT genotype
      carried the highest Type 1 diabetes risk HLA genotype, i.e. DRB1*03:01/DR4
      (DRB1*0401, *04:05 or *04:02), compared with 29.4% (27/92) of those without it
      (P=0.023). The DRB1*03:01 allele was present in 15.4% (2/13) of individuals with
      the single nucleotide polymorphism, compared with 59.8% (55/92) of those without
      it (P=0.003). Analyses restricted to autoantibody-positive individuals (n=80)
      yielded similar results. The HLA DRB1*15:01 allele, which affords dominant
      protection against Type 1 diabetes, was found in one participant, who had
      multiple islet autoantibodies and carried the rs7903146 TT genotype. CONCLUSIONS:
      These findings further support the hypothesis that TCF7L2 gene variation
      contributes to diabetogenesis in a subset of young people with Type 1 diabetes,
      opening possible new pathways for therapy and prevention.

PMID- 27027644
TI  - Enantioselective Trifluoromethylthiolating Lactonization Catalyzed by an Indane
      Based Chiral Sulfide.
AB  - Enantioselective trifluoromethylthiolation, especially of alkenes, is a
      challenging task. In this work, we have developed an efficient approach for
      enantioselective trifluoromethylthiolating lactonization by designing an indane
      based bifunctional chiral sulfide catalyst and a shelf-stable electrophilic SCF3
      reagent. The desired products were formed with diastereoselectivities of >99:1
      and good to excellent enantioselectivities. The transformation represents the
      first enantioselective trifluoromethylthiolation of alkenes and the first
      enantioselective trifluoromethylthiolation that is enabled by a catalyst with a
      Lewis basic sulfur center.

PMID- 27027643
TI  - Limited reduction of ferrihydrite encrusted by goethite in freshwater sediment.
AB  - Many physical and chemical processes control the extent of Fe(III) oxyhydroxide
      reduction by dissimilatory Fe(III)-reducing bacteria. The surface precipitation
      of secondary Fe minerals on Fe(III) oxyhydroxides limits the extent of microbial
      Fe(III) reduction, but this phenomenon has not yet been observed in nature. This
      paper reports the observation of secondary Fe-mineral (goethite) encrustation on
      ferrihydrite surface within freshwater sediment up to 10 cm deep. The sediment
      surface was characterized by the predominance of ferrihydrites with biogenic
      stalks and sheaths. An Fe(II)-oxidizing bacterium (Gallionellaceae) was detected
      by 16S rRNA gene analysis at sediment depths of 1 and 2 cm. Fe(2+) concentration
      in the sediment pore water was relatively higher at 2-4 cm depths. The 16S rRNA
      genes affiliated with dissimilatory Fe(III)-reducing bacteria were detected at 1,
      2, and 4 cm depths. The results of the Fe K-edge extended X-ray absorption fine
      structure (EXAFS) analysis suggested the presence of goethite and siderite at
      depths below 3 cm. However, the change in the Fe-mineral composition was
      restricted to sediment depths between 3 and 4 cm, despite the presence of
      abundant ferrihydrite at depths below 4 cm. An increase in CH4 concentration was
      observed at deeper than 6 cm. Stable isotopic analysis of CH4 in the pore water
      indicated that acetoclastic CH4 occurred at depths below 7 cm. Transmission
      electron microscope observations suggested the presence of goethite and siderite
      on stalks and sheaths at depths below 3 cm. Results from conversion electron
      yield EXAFS analysis suggested that goethite dominated at 10 cm depth, thereby
      indicating that ferrihydrite was encrusted by goethite at this depth. Moreover,
      the incomplete reduction of ferrihydrite below depths of 4 cm was not due to the
      lack of organic carbon, but was possibly due to the surface encrustation of
      goethite on ferrihydrite.

PMID- 27027645
TI  - Increased toxic urinary cations in males with interstitial cystitis: a possible
      cause of bladder symptoms.
AB  - PURPOSE: To identify and quantify toxic urinary cations in male patients with
      bladder pain syndrome/interstitial cystitis versus male controls, to compare them
      in symptomatic patients to those significantly improved, and to evaluate
      cytotoxicity of these cations to cultured urothelial cells to determine whether
      Tamm-Horsfall protein (THP) can neutralize the cations. METHODS: Isolation of
      cationic fraction (CFs) was achieved by solid phase extraction on urine specimens
      of 51 male patients with IC and 33 male controls. C18 reverse-phase high
      performance liquid chromatography was used to profile and quantify cationic
      metabolites. Major CF peaks were identified by liquid chromatography-tandem mass
      spectrometry. HTB-4 urothelial cells were used to determine the cytotoxicity of
      CFs, individual metabolites, and of metabolite mixture with THP of patient versus
      THP of control subject. RESULTS: CF content was significantly higher in patients
      compared to controls (p < 0.001). Patients had higher levels of modified
      nucleosides, amino acids, and their derivatives compared to controls.
      Cytotoxicity for control versus patient mean (SEM) percent was 1.7 (2.9) % versus
      63.0 (3.7) %, respectively, (p < 0.001). Cytotoxicity of metabolites was reduced
      in the presence of THP of control compared to THP of patient (p < 0.001).
      CONCLUSIONS: Patients with IC had significantly higher levels of cationic
      metabolites with higher cytotoxicity compared to controls. THP of these patients
      had reduced ability to sequester cytotoxicity of cationic metabolites. Patients
      who significantly improved on therapy had the same levels and toxicity of
      cationic metabolites as symptomatic males, suggesting that these cations may be
      the cause of epithelial dysfunction in IC.

PMID- 27027646
TI  - Characterisation of the yeast and mould biota in traditional white pickled
      cheeses by culture-dependent and independent molecular techniques.
AB  - Artisanal white pickled cheese of Western Serbia is a product of complex
      microbial community which detection by culture-dependent method only is hampered
      by its limitations. Thus, in the present study, we used a culture-independent,
      semi-quantitative technique based on construction of an internal transcribed
      spacer (ITS)-clone library from metagenomic DNA. This approach, based on direct
      DNA extraction followed by amplification of fungal internal transcribed regions
      (ITS) cloned into plasmid and restricted by endonucleases, revealed greater
      species richness in analysed cheeses and their by-products (17 species in total)
      compared to the more commonly used techniques of the culture-dependent method (8
      species) and LSU-DGGE (10 species). The most frequently occurring yeast species
      which are commonly associated with cheeses production were Debaryomyces hansenii,
      Kluyveromyces lactis and Candida zeylanoides. On the other hand, Yarrowia
      lipolytica and Galactomyces geotrichum were detected only in one cheese sample.
      Moreover, some species, mainly moulds (Filobasidium globisporum, Cladosporium
      sp., Aspergillus sp. or Alternaria sp.) were identified only by culture
      independent methods. The discrepancies between the techniques were confirmed by
      low correlation factor and by different indices of general biodiversity and
      dominance of species. The ITS-clone library approach provides the opportunity to
      analyse complex fungal communities associated with food products.

PMID- 27027647
TI  - Skull shapes of the Lissodelphininae: radiation, adaptation and asymmetry.
AB  - Within Delphinidae, the sub-family Lissodelphininae consists of 8 Southern Ocean
      species and 2 North Pacific species. Lissodelphininae is a result of recent
      phylogenetic revisions based on molecular methods. Thus, morphological radiation
      within the taxon has not been investigated previously. The sub-family consists of
      ecologically diverse groups such as (1) the Cephalorhynchus genus of 4 small
      species inhabiting coastal and shelf waters, (2) the robust species in the
      Lagenorhynchus genus with the coastal La. australis, the offshore La. cruciger,
      the pelagic species La. obscurus and La. obliquidens, and (3) the morphologically
      aberrant genus Lissodelphis. Here, the shapes of 164 skulls from adults of all 10
      species were compared using 3-dimensional geometric morphometrics. The
      Lissodelphininae skulls were supplemented by samples of Lagenorhynchus
      albirostris and Delphinus delphis to obtain a context for the variation found
      within the subfamily. Principal components analysis was used to map the most
      important components of shape variation on phylogeny. The first component of
      shape variation described an elongation of the rostrum, lateral and dorsoventral
      compression of the neurocranium and smaller temporal fossa. The two Lissodelphis
      species were on the high extreme of this spectrum, while Lagenorhynchus
      australis, La. cruciger and Cephalorhynchus heavisidii were at the low extreme.
      Along the second component, La. cruciger was isolated from the other species by
      its expanded neurocranium and concave facial profile. Shape variation supports
      the gross phylogenetic relationships proposed by recent molecular studies.
      However, despite the great diversity of ecology and external morphology within
      the subfamily, shape variation of the feeding apparatus was modest, indicating a
      similar mode of feeding across the subfamily. All 10 species were similar in
      their pattern of skull asymmetry, but interestingly, two species using narrowband
      high frequency clicks (La. cruciger and C. hectori) were among the most
      asymmetric species, contradicting previous interpretations of odontocete skull
      asymmetry. J. Morphol. 277:776-785, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27027648
TI  - Preface.

PMID- 27027649
TI  - Do Public Involvement Activities in Biomedical Research and Innovation Recruit
      Representatively? A Systematic Qualitative Review.
AB  - BACKGROUND: Public involvement activities (PIAs) may contribute to the governance
      of ethically challenging biomedical research and innovation by informing,
      consulting with and engaging the public in developments and decision-making
      processes. For PIAs to capture a population's preferences (e.g. on issues in
      whole genome sequencing, biobanks or genome editing), a central methodological
      requirement is to involve a sufficiently representative subgroup of the general
      public. While the existing literature focusses on theoretical and normative
      aspects of 'representation', this study assesses empirically how such
      considerations are implemented in practice. It evaluates how PIA reports describe
      representation objectives, the recruitment process and levels of representation
      achieved. METHODS: PIA reports were included from a systematic literature search
      if they directly reported a PIA conducted in a relevant discipline such as
      genomics, biobanks, biotechnology or others. PIA reports were analyzed with
      thematic text analysis. The text analysis was guided by an assessment matrix
      based on PIA-specific guidelines and frameworks. RESULTS: We included 46 relevant
      reports, most focusing on issues in genomics. 27 reports (59%) explicitly
      described representation objectives, though mostly without adjusting eligibility
      criteria and recruiting methods to the specific objective. 11 reports (24%)
      explicitly reported to have achieved the intended representation; the rest either
      reported failure or were silent on this issue. CONCLUSION: Representation of
      study samples in PIAs in biomedical research and innovation is currently not
      reported systematically. Improved reporting on representation would not only
      improve the validity and value of PIAs, but could also contribute to PIA results
      being used more often in relevant policy and decision-making processes.

PMID- 27027650
TI  - Adaptive dose modification for phase I clinical trials.
AB  - Most phase I dose-finding methods in oncology aim to find the maximum-tolerated
      dose from a set of prespecified doses. However, in practice, because of a lack of
      understanding of the true dose-toxicity relationship, it is likely that none of
      these prespecified doses are equal or reasonably close to the true maximum
      tolerated dose. To handle this issue, we propose an adaptive dose modification
      (ADM) method that can be coupled with any existing dose-finding method to
      adaptively modify the dose, when it is needed, during the course of dose finding.
      To reflect clinical practice, we divide the toxicity probability into three
      regions: underdosing, acceptable, and overdosing regions. We adaptively add a new
      dose whenever the observed data suggest that none of the investigational doses
      are likely to be located in the acceptable region. The new dose is estimated via
      a nonparametric dose-toxicity model based on local polynomial regression. The
      simulation study shows that ADM substantially outperforms the similar existing
      method. We applied ADM to a phase I cancer trial. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27027651
TI  - Calling for a re-evaluation of the data required to credibly demonstrate a dental
      student is safe and ready to practice.

PMID- 27027652
TI  - The cheating liver: imaging of focal steatosis and fatty sparing.
AB  - Focal steatosis and fatty sparing are a frequent finding in liver imaging, and
      can mimic solid lesions. Liver regional variations in the degree of fat
      accumulation can be related to vascular anomalies, metabolic disorders, use of
      certain drugs or coexistence of hepatic masses. CT and MRI are the modalities of
      choice for the noninvasive diagnosis of hepatic steatosis. Knowledge of CT and
      MRI appearance of focal steatosis and fatty sparing is crucial for an accurate
      diagnosis, and to rule-out other pathologic processes. This paper will review the
      CT and MRI techniques for the diagnosis of hepatic steatosis and the CT and MRI
      features of common and uncommon causes of focal steatosis and fatty sparing. 

PMID- 27027653
TI  - Comparison of QT Interval Readings in Normal Sinus Rhythm Between a Smartphone
      Heart Monitor and a 12-Lead ECG for Healthy Volunteers and Inpatients Receiving
      Sotalol or Dofetilide.
AB  - INTRODUCTION: A variety of medications ranging from antiarrhythmics to
      psychotropics, as well as conditions such as bradycardia, can prolong the QT
      interval, increasing the risk for life-threatening arrhythmias. Monitoring the
      corrected QT interval (QTc) is therefore critical for patient safety. The recent
      development of smart phone heart monitors (SHM) may allow for easier QTc
      monitoring. We sought to evaluate the accuracy of an SHM for assessing the QTc,
      as compared to the standard 12-lead ECG. METHODS AND RESULTS: We compared the QTc
      interval in lead-I and lead-II between an SHM and 12-lead ECG. Healthy volunteers
      and hospitalized patients in sinus rhythm being loaded on dofetilide or sotalol
      were included. Manual and automatic measurements were studied. Across 99 healthy
      volunteers, the SHM QTc demonstrated good agreement (bias = 4 milliseconds,
      standard deviation of bias = 11 milliseconds) compared to the 12-lead ECG, using
      the Bland-Altman method of agreement. Across all hospitalized patients, the SHM
      was capable of demonstrating QTc prolongation. Between the 12-lead ECG and SHM,
      lead-I measurements had reasonable agreement (bias = 3 milliseconds, standard
      deviation of bias = 46 milliseconds). A QTc of > 500 milliseconds was associated
      with a higher likelihood (OR = 12.0; 95% CI 1.5-111.4; P = 0.02) to not achieve
      perfect agreement. CONCLUSION: The SHM is accurate in measuring QTc interval in
      sinus rhythm when compared to 12-lead ECG in healthy volunteers. For patients
      receiving QT prolonging antiarrhythmics, SHM is capable of detecting QTc
      prolongation, and lead-I of the SHM is most accurate in measuring the QTc if <
      500 milliseconds.

PMID- 27027654
TI  - Erratum.

PMID- 27027655
TI  - Potential Usefulness of BMD and Bone Turnover Monitoring of Zoledronic Acid
      Therapy Among Women With Osteoporosis: Secondary Analysis of Randomized
      Controlled Trial Data.
AB  - We aimed to compare the clinical validity and the detectability of response of
      short-term changes in bone mineral density (BMD; hip and spine) and bone turnover
      markers (serum PINP and CTX) through secondary analysis of trial data. We
      analyzed data on 7765 women with osteoporosis randomized to 5-mg once-yearly
      infusions of zoledronic acid or placebo in the Health Outcomes and Reduced
      Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT;
      trial ran from 2002 to 2006) and the first extension trial (trial ran from 2006
      to 2009). We assessed the clinical validity and detectability of response for 1
      year measurements of the following monitoring tests: total hip and lumbar spine
      BMD, serum N-terminal propeptide of type I collagen (sPINP), and serum C
      telopeptide of type I collagen (sCTX; 6-month measurement used). Clinical
      validity was assessed by examining prediction of clinical fracture in Cox models;
      detectability of response to treatment was assessed by the ratio of signal to
      noise, estimated from the distributions of change in zoledronic acid and placebo
      groups. Baseline measurements were available for 7683 women with hip BMD, 558
      with spine BMD, 1246 with sPINP, and 517 women with sCTX. Hip BMD and sPINP
      ranked highly for prediction of clinical fracture, whereas sPINP and sCTX ranked
      highly for detectability of response to treatment. Serum PINP had the highest
      overall ranking. In conclusion, serum PINP is potentially useful in monitoring
      response to zoledronic acid. Further research is needed to evaluate the effects
      of monitoring PINP on treatment decisions and other clinically relevant outcomes.
      (c) 2016 American Society for Bone and Mineral Research.

PMID- 27027656
TI  - The Correlation Between Breastfeeding Success in the Early Postpartum Period and
      the Perception of Self-Efficacy in Breastfeeding and Breast Problems in the Late
      Postpartum.
AB  - INTRODUCTION: The research was conducted to determine the correlation between
      breastfeeding success in the early postpartum period and the perception of self
      efficacy in breastfeeding and breast problems in late postpartum. METHODS: This
      analytic and cross-sectional research was carried out at Aydin Obstetrics and
      Gynecology and Children's Diseases Hospital. Three hundred twenty-seven primipara
      mothers who had delivered a single baby of healthy term at 37 or more gestational
      weeks with no previous experience with breastfeeding and who agreed to cooperate
      participated in the research. RESULTS: The mothers' mean gestational week of
      delivery was 39.25 +/- 1.10 weeks, and it was found that 56.0% had delivered by
      cesarean section and 57.0% had started to breastfeed immediately after the birth.
      The mothers' LATCH mean score was 6.55 +/- 0.86; their postnatal breastfeeding
      self-efficacy mean score was found to be 59.10 +/- 7.21. Mothers who had high
      success in breastfeeding at early postpartum were found to experience fewer
      problems with their breasts (Z = -2.65, p < 0.05), gave birth by vaginal delivery
      (Z = -2.88, p < 0.05), and had not received anesthesia during the delivery (Z = 
      2.52, p < 0.05). In the correlation analysis, it was seen that mothers with high
      success in breastfeeding also had high self-efficacy scores (r = 0.210, p =
      0.003). CONCLUSION: The results of the research indicated that breastfeeding
      success in the early postpartum period reduced breast problems and increased the
      perception of breastfeeding self-efficacy in the late postpartum period.

PMID- 27027657
TI  - Sick Leave and Disability Across Three Decades After a Major Disaster.
AB  - Extended functional impairment characterized by sick leave and disability after a
      single disaster has not been documented before. This prospective, longitudinal,
      case-control study applied growth mixture modeling to predict trajectories of
      functional impairment in oil rig workers, survivors (n = 68) and a matched
      comparison group (n = 84), over 27 years after the 1980 North Sea oil rig
      disaster. In the initial 12 years post-disaster, survivors displayed higher rates
      of functional impairment than the comparison group. A minor group of survivors (n
      = 8, 11.8%) demonstrated persistent functional impairment from the start and
      remained unable to work during the subsequent three decades. Long-term sick leave
      and disability were related to perceived peritraumatic death threat and a
      propensity towards social withdrawal. Most survivors (n = 60) revealed no major
      functional impairment. The study indicates that functional impairment should be
      counteracted in the early support after a single disaster.

PMID- 27027658
TI  - When Partial Hospitalization Fails: Risk Factors for Inpatient Hospitalization.
AB  - Partial hospitalization is an understudied bridge between outpatient and
      inpatient care. One of its primary functions is to prevent the need for inpatient
      hospitalization. We examined potential demographic and clinical risk factors for
      inpatient hospitalization for current partial hospital patients. We conducted
      separate multiple logistic regression analyses for patients referred from
      inpatient care and the community. For individuals referred from inpatient care,
      suicidal ideation and greater psychotic symptoms upon admission to the partial
      program were associated with acute inpatient re-hospitalization. For individuals
      referred from the community, suicidal ideation and worse relationship functioning
      upon partial hospital admission were significant risk factors for inpatient
      hospitalization. Number of previous inpatient hospitalizations and greater
      substance abuse were not associated with inpatient hospitalization in either
      sample. Implications at the provider and program level are discussed.

PMID- 27027659
TI  - Childhood Precursors of Adult Borderline Personality Disorder Features: A
      Longitudinal Study.
AB  - This study identifies childhood personality traits that are precursors of adult
      Borderline Personality Disorder (BPD) features. In a longitudinal study,
      childhood personality traits were assessed at age 11 (N = 100) using the
      California Child Q-set (CCQ: Block and Block, 1980). A number of these Q-items
      were found to be significantly correlated (p < 0.001) with a prototype-based
      measure of BPD features at age 23. Factor analysis of these Q-items suggested
      that they could be characterized by two underlying personality dimensions:
      Impulsivity and Nonconformity/Aggression. The findings thus provide evidence that
      childhood personality traits predict adult BPD features. Identifying such
      childhood precursors provides an opportunity for early intervention.

PMID- 27027660
TI  - A Randomized, Controlled Pilot Study of a Single-Session Psychoeducation
      Treatment for Urban, Culturally Diverse, Trauma-Exposed Adults.
AB  - This randomized pilot study aimed to determine whether a single session of
      psychoeducation improved mental health outcomes, attitudes toward treatment, and
      service engagement among urban, impoverished, culturally diverse, trauma-exposed
      adults. Sixty-seven individuals were randomly assigned to a single-session
      psychoeducation treatment or a delayed treatment comparison control group. The
      control group was found to be superior to the treatment group at posttest with
      respect to symptoms of posttraumatic stress disorder, anxiety, and occupational
      and family disability. At follow-up, all participants had completed the
      psychoeducation treatment, and a mixed-effects model indicated significant
      improvements over time in symptoms of posttraumatic stress disorder, anxiety,
      depression, somatization, and attitudes toward treatment. Ninety-eight percent of
      the participants reported the psychoeducation was helpful at follow-up.
      Participants also reported a 19.1% increase in mental health service utilization
      at follow-up compared with baseline. Implications for treatment and future
      research are discussed.

PMID- 27027661
TI  - Substitution of Lithium for Magnesium, Zinc, and Aluminum in Li15 Si4 : Crystal
      Structures, Thermodynamic Properties, as well as (6) Li and (7) Li NMR
      Spectroscopy of Li15 Si4 and Li15-x Mx Si4 (M=Mg, Zn, and Al).
AB  - An investigation into the substitution effects in Li15 Si4 , which is discussed
      as metastable phase that forms during electrochemical charging and discharging
      cycles in silicon anode materials, is presented. The novel partial substitution
      of lithium by magnesium and zinc is reported and the results are compared to
      those obtained for aluminum substitution. The new lithium silicides Li14 MgSi4
      (1) and Li14.05 Zn0.95 Si4 (2) were synthesized by high-temperature reactions and
      their crystal structures were determined from single-crystal data. The magnetic
      properties and thermodynamic stabilities were investigated and compared with
      those of Li14.25 Al0.75 Si4 (3). The substitution of a small amount of Li in
      metastable Li15 Si4 for more electron-rich metals, such as Mg, Zn, or Al, leads
      to a vast increase in the thermodynamic stability of the resulting ternary
      compounds. The (6,7) Li NMR chemical shift and spin relaxation time T1 -NMR
      spectroscopy behavior at low temperatures indicate an increasing contribution of
      the conduction electrons to these NMR spectroscopy parameters in the series for 1
      3. However, the increasing thermal stability of the new ternary phases is
      accompanied by a decrease in Li diffusivity, with 2 exhibiting the lowest
      activation energy for Li mobility with values of 56, 60, and 62 kJ mol(-1) for 2,
      Li14.25 Al0.75 Si14 , and 1, respectively. The influence of the metastable
      property of Li15 Si4 on NMR spectroscopy experiments is highlighted. 

PMID- 27027662
TI  - Glucagon orchestrates stress-induced hyperglycaemia.
AB  - Hyperglycaemia is commonly observed on admission and during hospitalization for
      medical illness, traumatic injury, burn and surgical intervention. This transient
      hyperglycaemia is referred to as stress-induced hyperglycaemia (SIH) and
      frequently occurs in individuals without a history of diabetes. SIH has many of
      the same underlying hormonal disturbances as diabetes mellitus, specifically
      absolute or relative insulin deficiency and glucagon excess. SIH has the added
      features of elevated blood levels of catecholamines and cortisol, which are not
      typically present in people with diabetes who are not acutely ill. The
      seriousness of SIH is highlighted by its greater morbidity and mortality rates
      compared with those of hospitalized patients with normal glucose levels, and this
      increased risk is particularly high in those without pre-existing diabetes.
      Insulin is the treatment standard for SIH, but new therapies that reduce glucose
      variability and hypoglycaemia are desired. In the present review, we focus on the
      key role of glucagon in SIH and discuss the potential use of glucagon receptor
      blockers and glucagon-like peptide-1 receptor agonists in SIH to achieve target
      glucose control.

PMID- 27027663
TI  - Validation of a rapid test for HLA-B*58:01/57:01 allele screening to detect
      individuals at risk for drug-induced hypersensitivity.
AB  - AIM: In prevention of allopurinol and abacavir hypersensitivity, screening HLA
      B*58:01/57:01 has been highly recommended prior to commencing these therapies.
      Therefore, we aimed at developing and validating a rapid and robust screening
      method for HLA-B*58:01/57:01. MATERIALS & METHODS: Real-time polymerase chain
      reaction with TaqMan probes was employed to detect HLA-B*58:01/57:01. RESULTS:
      The newly developed assay has the sensitivity of 100% (95% CI: 79.4-100.0%), the
      specificity of 98.8% (95% CI: 93.6-99.9%), the positive predictive value of 94.1%
      (95% CI: 71.3-99.9%) and the negative predictive value of 100.0% (95% CI: 95.7
      100.0%). The lowest limit of detection is 0.04 ng/ul of DNA. CONCLUSION: The
      present method is a rapid and robust assay that is appropriate for screening of
      HLA-B*58:01/*57:01 alleles.

PMID- 27027664
TI  - Mutually Exclusive Formation of G-Quadruplex and i-Motif Is a General Phenomenon
      Governed by Steric Hindrance in Duplex DNA.
AB  - G-Quadruplex and i-motif are tetraplex structures that may form in opposite
      strands at the same location of a duplex DNA. Recent discoveries have indicated
      that the two tetraplex structures can have conflicting biological activities,
      which poses a challenge for cells to coordinate. Here, by performing innovative
      population analysis on mechanical unfolding profiles of tetraplex structures in
      double-stranded DNA, we found that formations of G-quadruplex and i-motif in the
      two complementary strands are mutually exclusive in a variety of DNA templates,
      which include human telomere and promoter fragments of hINS and hTERT genes. To
      explain this behavior, we placed G-quadruplex- and i-motif-hosting sequences in
      an offset fashion in the two complementary telomeric DNA strands. We found
      simultaneous formation of the G-quadruplex and i-motif in opposite strands,
      suggesting that mutual exclusivity between the two tetraplexes is controlled by
      steric hindrance. This conclusion was corroborated in the BCL-2 promoter
      sequence, in which simultaneous formation of two tetraplexes was observed due to
      possible offset arrangements between G-quadruplex and i-motif in opposite
      strands. The mutual exclusivity revealed here sets a molecular basis for cells to
      efficiently coordinate opposite biological activities of G-quadruplex and i-motif
      at the same dsDNA location.

PMID- 27027665
TI  - Gene aberrations for precision medicine against lung adenocarcinoma.
AB  - Lung adenocarcinoma (LADC), the most frequent histological type of lung cancer,
      is often triggered by an aberration in a driver oncogene in tumor cells. Examples
      of such aberrations are EGFR mutation and ALK fusion. Lung adenocarcinoma
      harboring such mutations can be treated with anticancer drugs that target the
      aberrant gene products. Additional oncogene aberrations, including RET, ROS1, and
      NRG1 fusions, skipping of exon 14 of MET, and mutations in BRAF, HER2, NF1, and
      MEK1, were recently added to the list of such "druggable" driver oncogene
      aberrations, and their responses to targeted therapies are currently being
      evaluated in clinical trials. However, approximately 30% and 50% of LADCs in
      patients in Japan and Europe/USA, respectively, lack the driver oncogene
      aberrations listed above. Therefore, novel therapeutic strategies, such as those
      that exploit the vulnerabilities of cancer cells with non-oncogene aberrations,
      are urgently required. This review summarizes the current status of research on
      precision medicine against LADC and enumerates the research priorities for the
      near future. 

PMID- 27027666
TI  - Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry.
AB  - OBJECTIVES: Transcranial direct current stimulation (tDCS) is a noninvasive brain
      stimulation technique that consists of applying a weak electric current over the
      scalp to modulate cortical excitability. tDCS has been extensively investigated
      in adults with psychiatric disorders. The aim of this study was to review the
      current literature regarding the use of tDCS in children and adolescents with
      psychiatric disorders. METHODS: We searched MEDLINE and EMBASE databases for
      studies evaluating the safety and efficacy of tDCS in children and adolescents
      from age 0 to 18 years with psychiatric disorders. RESULTS: We found six studies
      that evaluated patients with different psychiatric disorders, with diverse study
      designs and stimulation parameters, including three small randomized clinical
      trials (RCTs), one evaluating childhood-onset schizophrenia, one RCT with
      patients with autism spectrum disorders (ASD), and one study in attention
      deficit/hyperactivity disorder (ADHD); three open-label studies, two evaluating
      patients with ASD, and one study of feasibility of the technique in children and
      adolescents with language disorders and diverse psychiatric disorders, including
      ASD, intellectual disability, and ADHD. We also found three studies of dosage
      considerations in the general pediatric population. The technique was well
      tolerated, with no reports of serious side effects. CONCLUSION: Preliminary
      research suggests that tDCS may be well tolerated and safe for children and
      adolescents with psychiatric and neurodevelopmental disorders. Nevertheless,
      because the literature regarding tDCS in child and adolescent psychiatry is
      scarce and there exist limited numbers of randomized controlled trials, it is not
      possible to draw definite conclusions. Future studies should investigate the
      technique with regard to specific psychiatric conditions in comparison with
      standard treatments. In addition, long-term efficacy and safety should be
      monitored.

PMID- 27027667
TI  - A systematic review and meta-analysis of dressings used for wound healing: the
      efficiency of honey compared to silver on burns.
AB  - BACKGROUND: Honey has the antibacterial effect of silver without the toxic effect
      of silver on the skin. Even so, silver is the dominant antibacterial dressing
      used in wound healing. OBJECTIVES: To evaluate the healing effects of honey
      dressings compared to silver dressings for acute or chronic wounds. DESIGN: A
      systematic review with meta-analysis. METHOD: The search, conducted in seven
      databases, resulted in six randomised controlled trial studies from South Asia
      focusing on antibacterial properties and healing times of honey and silver.
      RESULT: Honey was more efficacious for wound healing than silver, as measured in
      the number of days needed for wounds to heal (pooled risk difference -20, 95% CI 
      0.29 to -0.11, p < .001). Honey turned out to have more antibacterial qualities
      than silver. CONCLUSION: All the included studies based on burns showed the
      unequivocal result that honey had an even more positive effect than silver on
      wound healing.

PMID- 27027668
TI  - Accelerated (18 mW/cm(2)) Corneal Cross-Linking for Progressive Keratoconus: 18
      Month Results.
AB  - PURPOSE: The aim of this study is to report the results of 18 months of follow-up
      after treatment with accelerated (18 mW/cm(2)) corneal cross-linking in patients
      with progressive keratoconus. METHODS: Forty-two eyes of 42 patients with
      progressive keratoconus were included in this retrospective study. All patients
      underwent accelerated corneal cross-linking at an irradiance of 18 mW/cm(2) for 5
      min (total surface dose 5.4 J/cm(2)). Visual acuity, topographic findings (Kflat,
      Ksteep, Kaverage, and apical keratometry), and central corneal thickness were
      evaluated during the 18-month follow-up period. RESULTS: The mean +/- standard
      deviation age of the 16 female and 26 male patients was 24.28 +/- 6.32 years
      (range 14-36). Uncorrected distance visual acuity improved clinically significant
      from 0.52 +/- 0.31 to 0.44 +/- 0.25 logMAR (P = 0.031), and corrected distance
      visual acuity improved clinically significant from 0.34 +/- 0.21 to 0.28 +/- 0.19
      logMAR (P = 0.018). At the last examination during the follow-up period, the flat
      keratometry (Kflat) decreased from a baseline of 45.65 +/- 2.71 to 45.41 +/- 2.72
      diopters (D) (P = 0.001), the steep keratometry (Ksteep) decreased from 49.20 +/-
      3.54 to 48.96 +/- 3.43 D (P = 0.023), and apical keratometry decreased from 56.62
      +/- 6.43 to 55.19 +/- 5.69 D (P = 0.001), all of them were clinically significant
      at the 18-month visit. The preoperative values of central corneal thickness
      changed from 458.95 +/- 38.79 to 461.85 +/- 41.36 MUm 18 months after the
      operation (P = 0.476). CONCLUSION: The accelerated corneal cross-linking was
      found to be effective for the stabilization of progressive keratoconus during the
      18 months of follow-up visits.

PMID- 27027669
TI  - Assessment of Important Sensory Attributes of Millet Based Snacks and Biscuits.
AB  - There is an increasing push by consumers for new food products that can provide
      health benefits. To develop these products, sometimes it is necessary to look to
      alternative crops, 1 of which is millet. For millet to be successfully adopted by
      consumers, it is necessary to identify and develop product types that are
      acceptable to North Americans. Biscuits and extruded snacks were produced using
      varying amounts of refined proso millet flour (0%, 25%, 75%, and 100%). Sensory
      analysis was conducted on 8 products (4 types of biscuits and 4 types of extruded
      snack) in 2 separate tests (1 for biscuits and 1 for snacks). Preferred Attribute
      Elicitation (PAE), a relatively new sensory method, was used to determine
      attributes affecting liking of the products. Results indicated that as the amount
      of millet in the biscuits and extruded snacks increased, the liking of the
      flavor, texture and overall liking decreased. Millet contributed to a bitter
      taste and bitter aftertaste, and resulted in gritty and dry food products.
      Further work is required to refine the products tested as well as to identify
      further products that can be added to the diet in order to take advantage of the
      health benefits that millet provides. 

PMID- 27027670
TI  - Safety and toxicity of nanomaterials for ocular drug delivery applications.
AB  - Multifunctional nanomaterials are rapidly emerging for ophthalmic delivery of
      therapeutics to facilitate safe and effective targeting with improved patient
      compliance. Because of their extremely high area to volume ratio, nanomaterials
      often have physicochemical properties that are different from those of their
      larger counterparts. There exists a complex relationship between the
      physicochemical properties (composition, size, shape, charge, roughness, and
      porosity) of the nanomaterials and their interaction with the biological system.
      The eye is a very sensitive accessible organ and is subjected to intended and
      unintended exposure to nanomaterials. Currently, various ophthalmic formulations
      are available in the market, while some are underway in preclinical and clinical
      phases. However, the data on safety, efficacy, and toxicology of these advanced
      nanomaterials for ocular drug delivery are sparse. Focus of the present review is
      to provide a comprehensive report on the safety, biocompatibility and toxicities
      of nanomaterials in the eye.

PMID- 27027671
TI  - End-of-Life Discussion, Patient Understanding and Determinants of Preferences in
      Very Severe COPD Patients: A Multicentric Study.
AB  - Discussion about patients' end-of-life (E-o-L) preferences should be part of the
      routine practice. Using a semi-structured interview with a scenario-based
      decision, we performed a prospective multicentre study to elicit the patients' E
      o-L preferences in very severe chronic obstructive pulmonary disease (COPD). We
      also checked their ability to retain this information and the respect of their
      decisions when they die. Forty-three out of ninety-one of the eligible patients
      completed the study. The choice of E-o-L practice was equally distributed among
      the three proposed options: endotracheal intubation (ETI), 'ceiling' non-invasive
      ventilation (NIV), and palliation of symptoms with oxygen and morphine. NIV and
      ETI were more frequently chosen by patients who already experienced them. ETI
      preference was also associated with the use of anti-depressant drugs and a low
      educational level, while a higher educational level and a previous discussion
      with a pneumologist significantly correlated with the preference for oxygen and
      morphine. Less than 50% of the patients retained a full comprehension of the
      options at 24 hours. About half of the patients who died in the follow-up period
      were not treated according to their wishes. In conclusion, in end-stage COPD more
      efforts are needed to improve communication, patients' knowledge of the disease
      and E-o-L practice.

PMID- 27027673
TI  - Universal Access to Health and Universal Health Coverage: Nursing contributions.

PMID- 27027672
TI  - An assessment of algorithms to estimate respiratory rate from the
      electrocardiogram and photoplethysmogram.
AB  - Over 100 algorithms have been proposed to estimate respiratory rate (RR) from the
      electrocardiogram (ECG) and photoplethysmogram (PPG). As they have never been
      compared systematically it is unclear which algorithm performs the best. Our
      primary aim was to determine how closely algorithms agreed with a gold standard
      RR measure when operating under ideal conditions. Secondary aims were: (i) to
      compare algorithm performance with IP, the clinical standard for continuous
      respiratory rate measurement in spontaneously breathing patients; (ii) to compare
      algorithm performance when using ECG and PPG; and (iii) to provide a toolbox of
      algorithms and data to allow future researchers to conduct reproducible
      comparisons of algorithms. Algorithms were divided into three stages: extraction
      of respiratory signals, estimation of RR, and fusion of estimates. Several
      interchangeable techniques were implemented for each stage. Algorithms were
      assembled using all possible combinations of techniques, many of which were
      novel. After verification on simulated data, algorithms were tested on data from
      healthy participants. RRs derived from ECG, PPG and IP were compared to reference
      RRs obtained using a nasal-oral pressure sensor using the limits of agreement
      (LOA) technique. 314 algorithms were assessed. Of these, 270 could operate on
      either ECG or PPG, and 44 on only ECG. The best algorithm had 95% LOAs of  -4.7
      to 4.7 bpm and a bias of 0.0 bpm when using the ECG, and  -5.1 to 7.2 bpm and 1.0
      bpm when using PPG. IP had 95% LOAs of  -5.6 to 5.2 bpm and a bias of  -0.2 bpm.
      Four algorithms operating on ECG performed better than IP. All high-performing
      algorithms consisted of novel combinations of time domain RR estimation and
      modulation fusion techniques. Algorithms performed better when using ECG than
      PPG. The toolbox of algorithms and data used in this study are publicly
      available. 

PMID- 27027674
TI  - Barriers to access to treatment for mothers with postpartum depression in primary
      health care centers: a predictive model.
AB  - OBJECTIVE: to develop a predictive model to evaluate the factors that modify the
      access to treatment for Postpartum Depression (PPD). METHODS: prospective study
      with mothers who participated in the monitoring of child health in primary care
      centers. For the initial assessment and during 3 months, it was considered:
      sociodemographic data, gyneco-obstetric data, data on the services provided,
      depressive symptoms according to the Edinburgh Postpartum Depression Scale (EPDS)
      and quality of life according to the Short Form-36 Health Status Questionnaire
      (SF-36). The diagnosis of depression was made based on MINI. Mothers diagnosed
      with PPD in the initial evaluation, were followed-up. RESULTS: a statistical
      model was constructed to determine the factors that prevented access to
      treatment, which consisted of: item 2 of EPDS (OR 0.43, 95%CI: 0.20-0.93) and
      item 5 (OR 0.48, 95%CI: 0.21-1.09), and previous history of depression treatment
      (OR 0.26, 95%CI: 0.61-1.06). Area under the ROC curve for the model=0.79; p-value
      for the Hosmer-Lemershow=0.73. CONCLUSION: it was elaborated a simple, well
      standardized and accurate profile, which advises that nurses should pay attention
      to those mothers diagnosed with PPD, presenting low/no anhedonia (item 2 of
      EPDS), scarce/no panic/fear (item 5 of EPDS), and no history of depression, as it
      is likely that these women do not initiate treatment.

PMID- 27027675
TI  - Access to surgical assistance: challenges and perspectives.
AB  - OBJECTIVE: to characterize the access to surgical assistance in Brazil. METHOD:
      documentary study, with a quantitative approach, developed from information of
      the Caixa Preta da Saude [Health Black Box] database, of the Brazilian Medical
      Association. RESULTS: in the one-year period 3773 cases related to health care in
      Brazil were recorded. There were 458 (12.3%) records on surgical assistance. Of
      these, most, 339 (74.1%), involved the lack of access in all regions of Brazil.
      The main access constraint was the prolonged waiting time for surgery. Other
      constraints were the excessive waiting for medical appointment with experts,
      doing examinations and cancellation of surgeries. CONCLUSION: the access to
      surgical assistance, by users of the Brazilian health system, is not widely
      guaranteed, reinforcing the need for integrated governmental actions,
      organization of the health care network, management of health care and human
      resources to overcome the challenges imposed to achieve the Universal Access to
      Health and Universal Health Coverage.

PMID- 27027677
TI  - Right to health: (in) congruence between the legal framework and the health
      system.
AB  - OBJECTIVE: to discuss the right to health, incorporation into the legal
      instruments and the deployment in practice in the National Health System in
      Mozambique. METHOD: this is a documentary analysis of a qualitative nature, which
      after thorough and interpretative reading of the legal instruments and articles
      that deal with the right to health, access and universal coverage, resulted in
      the construction of three empirical categories: instruments of humans rights and
      their interrelationship with the development of the right to health; the national
      health system in Mozambique; gaps between theory and practice in the
      consolidation of the right to health in the country. RESULTS: Mozambique ratified
      several international and regional legal instruments (of Africa) that deal with
      the right to health and which are ensured in its Constitution. However, their
      incorporation into the National Health Service have been limited because it can
      not provide access and universal coverage to health services in an equitable
      manner throughout its territorial extension and in the different levels of care.
      CONCLUSIONS: the implementation of the right to health is complex and will
      require mobilization of the state and political financial, educational,
      technological, housing, sanitation and management actions, as well as ensuring
      access to health, and universal coverage.

PMID- 27027676
TI  - Prevention of catheter-associated urinary tract infection: implementation
      strategies of international guidelines.
AB  - OBJECTIVE: to describe strategies used by health professionals on the
      implementation of the Centers for Disease Control and Prevention guidelines for
      the prevention of urinary infection related to catheterism. METHOD: systematic
      review on literature based on data from CINAHL(r), Nursing & Allied Health
      Collection, Cochrane Plus Collection, MedicLatina, MEDLINE(r), Academic Search
      Complete, ACS - American Chemical Society, Health Reference Center Academic,
      Nursing Reference Center, ScienceDirect Journals and Wiley Online Library. A
      sample of 13 articles was selected. RESULTS: studies have highlighted the
      decrease of urinary tract infection related to catheterism through reminder
      systems to decrease of people submitted to urinary catheterism, audits about
      nursing professionals practice and bundles expansion. CONCLUSION: the present
      review systemizes the knowledge of used strategies by health professionals on
      introduction to international recommendations, describing a rate decrease of such
      infection in clinical practice.

PMID- 27027678
TI  - Stigma and prejudice: the experience of crack users.
AB  - OBJECTIVE: to evaluate the stigma and prejudice experienced by crack users in
      their social context. METHOD: a qualitative study developed through the Fourth
      Generation Evaluation, conducted with four interest groups (ten users, eleven
      families, eight employees, and seven managers), components of the mental health
      care network. For data collection, we used observation and individual interview.
      The analysis was performed through the constant comparative method. RESULTS:
      crack users suffer prejudice and are stigmatized as those who do not fit in the
      systems established by society (without family links, formal employment and
      dwelling), and are thus excluded. They exhibit undisciplined behavior and,
      therefore, are discriminated, marginalized and considered as criminals, losing
      their uniqueness and living in vulnerable situations. CONCLUSION: the evaluation
      process emphasized the need to demystify the social imaginary that demonizes the
      chemically dependent, being thus important to develop public policies with
      actions focused on health, prevention, information and combat to stigma.

PMID- 27027679
TI  - Nursing workloads in family health: implications for universal access.
AB  - OBJECTIVE: to identify the workloads of nursing professionals of the Family
      Health Strategy, considering its implications for the effectiveness of universal
      access. METHOD: qualitative study with nursing professionals of the Family Health
      Strategy of the South, Central West and North regions of Brazil, using
      methodological triangulation. For the analysis, resources of the Atlas.ti
      software and Thematic Content Analysis were associated; and the data were
      interpreted based on the labor process and workloads as theorical approaches.
      RESULTS: the way of working in the Family Health Strategy has predominantly
      resulted in an increase in the workloads of the nursing professionals, with
      emphasis on the work overload, excess of demand, problems in the physical
      infrastructure of the units and failures in the care network, which hinders its
      effectiveness as a preferred strategy to achieve universal access to health. On
      the other hand, teamwork, affinity for the work performed, bond with the user,
      and effectiveness of the assistance contributed to reduce their workloads.
      CONCLUSIONS: investments on elements that reduce the nursing workloads, such as
      changes in working conditions and management, can contribute to the effectiveness
      of the Family Health Strategy and achieving the goal of universal access to
      health.

PMID- 27027680
TI  - Survey on the use of health services by adult men: prevalence rates and
      associated factors.
AB  - OBJECTIVE: estimate the prevalence and identify factors associated with the use
      of health services by men between 20 and 59 years of age. METHOD: population
      based, cross-sectional domestic survey undertaken with 421 adult men, selected
      through systematic random sampling. The data were collected through a structured
      instrument and analyzed using descriptive and inferential statistics with
      multiple logistic regression. RESULTS: the prevalence rate of health service use
      during the three months before the interviews was 42.8%, being higher among
      unemployed men with a religious creed who used private hospitals more frequently,
      had been hospitalized in the previous 12 months and referred some disease.
      CONCLUSION: the prevalence of health service use by adult men does not differ
      from other studies and was considered high. It shows to be related with the need
      for curative care, based on the associated factors found.

PMID- 27027681
TI  - Migrant nurses in Brazil: demographic characteristics, migration flow and
      relationship with the training process.
AB  - OBJECTIVE: to analyze the migration of nurses in Brazil, describe the demographic
      characteristics of migrant nurses, the main migration flows, and establish
      relationships with the training process. METHOD: a descriptive, exploratory
      study, based on 2010 Census data. The data were analyzed using descriptive
      statistics. RESULT: there were 355,383 nurses in Brazil in 2010. Of these, 36,479
      (10.3%) reported having moved compared to the year 2005: 18,073 (5.1%) for
      intrastate migration, 17,525 (4.8%) interstate migration, and 871 (0.2%)
      international migration. Females (86.3%), Caucasians (65.2%), and unmarried
      (48.3%) nurses prevailed in the population, without considerable variation
      between groups according to migration situation. The findings indicate that the
      migration flows are driven by the training process for states that concentrate a
      greater number of courses and positions in undergraduate and graduate studies,
      and the motivation of employment opportunity in regions of economic expansion in
      the country. CONCLUSION: it is necessary to deepen the discussion on the movement
      of nurses in Brazil, their motivations, and international migration.

PMID- 27027682
TI  - Glomerular cell crosstalk.
AB  - PURPOSE OF REVIEW: Glomerular filtration occurs in specialized, microscopic
      organelles. Each glomerulus contains unique cells and these cooperate to maintain
      normal filtration. Phenomenal adaptation is required for the glomerulus to
      respond to variable mechanical loads and this adaptation requires efficient
      communication between the resident cells. This review will focus on the latest
      discoveries related to signalling events that mediate the crosstalk between
      glomerular cells, and detail how disease processes can influence normal
      regulation. RECENT FINDINGS: New data indicate that the crosstalk between
      glomerular cells involves an increasing number of secreted signalling ligands
      that act in an autocrine or paracrine fashion. Furthermore, extended roles for
      some of the classical signalling molecules have been described and there is
      emerging evidence of therapeutic strategies to manipulate cellular crosstalk. The
      glomerular extracellular matrix harbours many of these signalling ligands, acting
      as a reservoir and presenting ligands to cell surface receptors. Signals can also
      be transferred between cells by extracellular vesicles and this is an emerging
      concept in cellular crosstalk. SUMMARY: Recent discoveries are building our
      understanding about glomerular cell crosstalk, and this review focuses on growth
      factors and signalling peptides, methods of delivery to target cells, and the
      potential for developing new therapies for glomerular disease.

PMID- 27027683
TI  - Novel Patterning Method for Silver Nanowire Electrodes for Thermal-Evaporated
      Organic Light Emitting Diodes.
AB  - Silver nanowires (AgNWs) mesh has been used as transparent electrodes in
      optoelectronic devices. However, the lack of practical patterning techniques for
      the random percolating nanowire network has limited its applications in devices
      where a well-defined pixel is required. Here, by controlling the surface wetting
      properties of a polydimethylsiloxane (PDMS) release template, we are able to
      pattern the random AgNWs network with uniform conducting property; and due to the
      hydrophobic recovery nature of PDMS, a multilayer patterning and transferring
      process can be realized, resulting in a fine-patterned, smooth, and uniform AgNWs
      mesh/poly(3,4-ethylenedioxythiophene) polystyrenesulfonate ( PEDOT: PSS)
      composite electrode. A thermal-evaporated organic light-emitting diode (OLED) is
      directly fabricated onto the patterned AgNWs/ PEDOT: PSS composite electrode. The
      device shows well-defined pixel edges and a uniformly lighted pixel area. A
      uniform OLED with very low leakage current is realized. The enhanced efficiency
      compared to the controlled device with prepatterned indium tin oxide (ITO)
      electrode is attributed to the scattering effects of the AgNWs electrode.

PMID- 27027685
TI  - Elastic Anisotropy Scenario for Cooperative Binding of Kinesin-Coated Beads on
      Microtubules.
AB  - Muto et al. reported in 2005 an observation called cooperative binding, according
      to which the initial binding of a bead covered with active kinesins on a
      microtubule filament was capable of favoring the subsequent binding of similar
      beads on the same filament up to distances of the order of a few microns. This
      positive bias is stronger ahead of the initially bound bead than behind. We
      explain this effect by combining the recently proposed notion of shear screening
      length with the notion of localized tubulin conformational transition induced by
      motor binding. Elastic terms linked to the polarity of protofilaments, up to now
      ignored, provide adequate description to the long-range elastic shear generated
      by motor binding. The subsequent binding is favored when and where the shear
      displacement of protofilaments meets the requirement for specific strong binding.
      We propose experimental tests of our model, which open the way to a new type of
      spectroscopy for biomolecular processes.

PMID- 27027684
TI  - Revascularization with percutaneous coronary intervention does not affect
      androgen status in males with chronic stable angina pectoris.
AB  - There is a clear association between low serum testosterone and coronary artery
      disease (CAD) in men. Hypotestosteronaemia is associated with accelerated
      atherosclerosis and a quarter of men with CAD are biochemically hypogonadal.
      Amongst those with CAD, hypotestosteronaemia is associated with increased
      mortality. Testosterone vasodilates coronary arteries, and exogenous testosterone
      reduces ischaemia. Whether hypotestosteronaemia is a cause or a consequence of
      CAD remains unanswered. The aim of this prospective observational study was to
      investigate whether coronary revascularization affected androgen status in men
      with stable angina pectoris. Twenty five men (mean age 62.7, SD 9.18) with
      angiographically significant CAD and symptomatic angina underwent full coronary
      revascularization by percutaneous coronary intervention. Androgen status and
      symptoms of angina, stress, depression and sexual function were assessed before,
      and at one and 6 months after the coronary revascularization. All patients
      underwent complete revascularization which was associated with a significant
      reduction in angina symptoms and ischaemia. No significant difference was seen in
      total testosterone (11.33 nmol/L baseline; 12.56, 1 month post; 13.04 at 6
      months; p = 0.08). A significant and sustained rise in sex hormone-binding
      globulin was seen (33.99 nm/L baseline; 36.11 nm/L 1 month post PCI; 37.94 nm/L
      at 6 months; p = 0.03) Overall, there was no significant alteration in any other
      marker of androgen status including free testosterone or bioavailable
      testosterone. There was no change in symptoms of anxiety, depression or sexual
      function. Coronary revascularization has no sustained effect on androgen status.
      This supports the hypothesis that hypotestosteronaemia is not a consequence of
      angina pectoris or myocardial ischaemia.

PMID- 27027686
TI  - Development and characterization of surface engineered PPI dendrimers for
      targeted drug delivery.
AB  - In this study, we reported folate-conjugated polypropylene imine dendrimers (FA
      PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH
      sensitive drug release, selective targeting to cancer cells, and anticancer
      activity. In the in vitro drug release studies this nanoconjugate of MTX showed
      initial rapid release followed by gradual slow release, and the drug release was
      found to be pH sensitive with greater release at acidic pH. The ex vivo
      investigations with human breast cancer cell lines, MCF-7, showed enhanced
      cytotoxicity of MTX-FA-PPI with significantly enhanced intracellular uptake. The
      biofate of nanoconjugate was determined in Wistar rat where MTX-FA-PPI showed
      37.79-fold increase in the concentration of MTX in liver after 24 h in comparison
      with free MTX formulation.

PMID- 27027687
TI  - Seebri Neohaler and Utibron Neohaler for COPD.

PMID- 27027688
TI  - Lumacaftor/ivacaftor (Orkambi) for cystic fibrosis.

PMID- 27027689
TI  - Cobimetinib (Cotellic) for metastatic melanoma.

PMID- 27027690
TI  - A recombinant C1 esterase inhibitor (Ruconest) for hereditary angioedema.

PMID- 27027691
TI  - Inhibitors and inducers of CYP enzymes and P-Glycoprotein.

PMID- 27027692
TI  - In brief: Dinutuximab (Unituxin) for high-risk neuroblastoma.

PMID- 27027693
TI  - In brief: Uridine triacetate (Xuriden) for hereditary orotic aciduria.

PMID- 27027694
TI  - The effect of insulin resistance and exercise on the percentage of CD16(+)
      monocyte subset in obese individuals.
AB  - Obesity is a low-grade chronic inflammation condition, and macrophages, and
      possibly monocytes, are involved in the pathological outcomes of obesity.
      Physical exercise is a low-cost strategy to prevent and treat obesity, probably
      because of its anti-inflammatory action. We evaluated the percentage of CD16(-)
      and CD16(+) monocyte subsets in obese insulin-resistant individuals and the
      effect of an exercise bout on the percentage of these cells. Twenty-seven
      volunteers were divided into three experimental groups: lean insulin sensitive,
      obese insulin sensitive and obese insulin resistant. Venous blood samples
      collected before and 1 h after an aerobic exercise session on a cycle ergometer
      were used for determination of monocyte subsets by flow cytometry. Insulin
      resistant obese individuals have a higher percentage of CD16(+) monocytes (14.8
      +/- 2.4%) than the lean group (10.0 +/- 1.3%). A positive correlation of the
      percentage of CD16(+) monocytes with body mass index and fasting plasma insulin
      levels was found. One bout of moderate exercise reduced the percentage of CD16(+)
      monocytes by 10% in all the groups evaluated. Also, the absolute monocyte count,
      as well as all other leukocyte populations, in lean and obese individuals,
      increased after exercise. This fact may partially account for the observed
      reduction in the percentage of CD16(+) cells in response to exercise. Insulin
      resistant, but not insulin-sensitive obese individuals, have an increased
      percentage of CD16(+) monocytes that can be slightly modulated by a single bout
      of moderate aerobic exercise. These findings may be clinically relevant to the
      population studied, considering the involvement of CD16(+) monocytes in the
      pathophysiology of obesity. Copyright (c) 2016 John Wiley & Sons, Ltd.
      SIGNIFICANCE OF THE STUDY: Obesity is now considered to be an inflammatory
      condition associated with many pathological consequences, including insulin
      resistance. It is proposed that insulin resistance contributes to the aggravation
      of the inflammatory dysfunction in obesity. The effect of obesity on the
      percentage of monocytes was previously observed in class II and III obese
      individuals who presented other alterations in addition to insulin resistance. In
      this study we observed that insulin-resistant obese individuals, but not insulin
      sensitive ones, had an increased percentage of CD14(+) CD16(+) monocytes. This
      fact shows that a dysfunction of the monocyte percentage in class I obese
      individuals is only seen when this condition is associated with insulin
      resistance.

PMID- 27027695
TI  - Glaucarubinone Combined with Gemcitabine Improves Pancreatic Cancer Survival in
      an Immunocompetent Orthotopic Murine Model.
AB  - BACKGROUND: Pancreatic cancer continues to have a poor survival rate with an
      urgent need for improved treatments. Glaucarubinone, a natural product first
      isolated from the seeds of the tree Simarouba glauca, has recently been
      recognized as having anti-cancer properties that may be particularly applicable
      to pancreatic cancer. METHODS: The effect of glaucarubinone on the growth and
      migration of murine pancreatic cancer cells was assessed by 3H-thymidine
      incorporation assay. The survival impact of glaucarubinone alone and in
      combination with gemcitabine chemotherapy was assessed using an immunocompetent
      orthotopic murine model of pancreatic cancer. RESULTS: Glaucarubinone inhibited
      the growth of the murine pancreatic cancer cell lines LM-P and PAN02. Treatment
      with either glaucarubinone or gemcitabine reduced proliferation in vitro and the
      combination was synergistic. The combination treatment improved survival two-fold
      compared to gemcitabine treatment alone (p = 0.046) in PAN02 cells. CONCLUSIONS:
      The synergistic inhibition by glaucarubinone and gemcitabine observed in vitro
      and the improved survival in vivo suggest that glaucarubinone may be a useful
      adjunct to current chemotherapy regimens.

PMID- 27027696
TI  - Researchers Turn to Canine Clinical Trials to Advance Cancer Therapies.

PMID- 27027697
TI  - Laparoscopic Antireflux Surgery in Patients with Connective Tissue Diseases.
AB  - Different connective tissue diseases (CTDs), such as dermatomyositis, mixed CTD,
      rheumatoid arthritis, polymyositis, lupus, and Behcet's, may affect the
      esophagus, impairing its motor function. The muscular atrophy and fibrosis caused
      by the autoimmune vasculitis and neuronal dysfunction affect the esophageal body
      and the lower esophageal sphincter, leading to a clinical presentation of
      dysphagia and gastroesophageal reflux disease (GERD). The belief that the
      impaired esophageal motility may negatively affect surgical outcome has led to
      the common recommendation of avoiding laparoscopic antireflux surgery (LARS) for
      fear of creating or worsening dysphagia. This review focuses on the evaluation of
      the outcome of LARS in patients with CTD. Specifically, this review shows that
      the literature on LARS and CTDs is scarce and most studies have a small number of
      patients and a short follow-up. Furthermore, a subanalysis of the outcome based
      on the type of CTD or the manometric profile is still elusive. In the setting of
      these limitations, it appears that results are good and comparable to those of
      patients with GERD and without a CTD. Morbidity and mortality are insignificant
      even considering the systemic manifestations of the CTD. LARS should not be
      denied to patients with CTD and GERD. 

PMID- 27027698
TI  - Reliability and responsiveness of measures of pain in people with osteoarthritis
      of the knee: a psychometric evaluation.
AB  - PURPOSE: To examine the fit between data from the Short Form McGill Pain
      Questionnaire (SF-MPQ-2) and the Rasch model, and to explore the reliability and
      internal responsiveness of measures of pain in people with knee osteoarthritis.
      METHODS: Participants with knee osteoarthritis completed the SF-MPQ-2,
      Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP) and
      painDETECT. Participants were sent the same questionnaires 3 and 6 months later.
      RESULTS: Fit to the Rasch model was not achieved for the SF-MPQ-2 Total scale.
      The Continuous subscale yielded adequate fit statistics after splitting item 10
      on uniform DIF for gender, and removing item 9. The Intermittent subscale fit the
      Rasch model after rescoring items. The Neuropathic subscale had relatively good
      fit to the model. Test-retest reliability was satisfactory for most scales using
      both original and Rasch scoring ranging from fair to substantial. Effect sizes
      ranged from 0.13 to 1.79 indicating good internal responsiveness for most scales.
      CONCLUSIONS: These findings support the use of ICOAP subscales as reliable and
      responsive measure of pain in people with knee osteoarthritis. The MPQ-SF-2
      subscales found to be acceptable alternatives. Implications for Rehabilitation
      The McGill Pain Questionnaire short version 2 is not a unidimensional scale in
      people with knee osteoarthritis, whereas three of the subscales are
      unidimensional. The McGill Pain Questionnaire short version 2 Affective subscale
      does not have good measurement properties for people with knee osteoarthritis.
      The McGill Pain Questionnaire short version 2 and the Intermittent and Constant
      Osteoarthritis Pain scales can be used to assess change over time. The painDETECT
      performs better as a screening measure than as an outcome measure.

PMID- 27027700
TI  - EEG neurofeedback effects in the treatment of adolescent anorexia nervosa.
AB  - A pre-post design including 22 females was used to evaluate the effectiveness of
      neurofeedback in the treatment of adolescent anorexia nervosa. Resting EEG
      measures and a psychological test-battery assessing eating behavior traits,
      clinical symptoms, emotionality, and mood were obtained. While both the
      experimental (n = 10) and control group (n = 12) received their usual maintenance
      treatment, the experimental group received 10 sessions of individual alpha
      frequency training over a period of 5 weeks as additional treatment. Significant
      training effects were shown in eating behavior traits, emotion regulation, and in
      relative theta power in the eyes closed condition. Although the results are
      limited due to the small sample size, these are the first empirical data
      demonstrating the benefits of neurofeedback as a treatment adjunct in individuals
      with anorexia nervosa. 

PMID- 27027699
TI  - Potential future risk of errors in medication administration recording.
AB  - RATIONALE, AIMS AND OBJECTIVES: The aim of this study is to adapt and assess the
      interrater reliability of a potential future risk matrix for medication errors in
      medication administration recording (ME-MAR). METHODS: The study was carried out
      in a teaching hospital. It was conducted in two phases. In the first phase, a
      consensus method was used in order to adapt the potential future risk matrix
      published by the National Patient Safety and Otero et al. to the ME-MAR. The
      consensus method consisted in a nominal group formed by four pharmacists. In the
      second phase, a multidisciplinary group of experts in patient safety assessed the
      reliability of the adapted matrix. Five raters evaluated 100 ME-MAR. Its
      reliability was evaluated using the kappa statistic. RESULTS: In the first phase,
      two meetings were necessary until consensus was reached to adapt the potential
      future risk matrix to the ME-MAR. For this purpose, the two following categories
      were defined: likelihood of ME-MAR's recurrence and most likely consequences of
      ME-MAR. The definition of each grade of likelihood of recurrence was based on the
      incidence of ME-MAR from an unpublished study carried out in our hospital. In
      order to determine the most likely consequences of ME-MAR, a two-dimensional
      matrix was designed, with severity per type of ME-MAR on one axis and the class
      of medication on the other. In the second phase, the reliability of the matrix
      was tested. The overall interrater agreement for the five raters was substantial
      at 0.68 (Confidence interval 95% 0.60-0.76). CONCLUSION: The adapted matrix of
      potential future risk to ME-MAR is reliable and can serve as a guide for future
      studies.

PMID- 27027702
TI  - Genomic and viral findings in two different primary Merkel cell carcinomas in a
      76-year-old woman.

PMID- 27027701
TI  - A new anthraquinone and eight constituents from Hedyotis caudatifolia Merr. et
      Metcalf: isolation, purification and structural identification.
AB  - Hedyotis caudatifolia Merr. et Metcalf. (HC), a folk medicine in Yao
      nationalities areas in China, was used to investigate the chemical constituents.
      Through silica gel and Sephadex LH-20 column chromatography, nine compounds were
      isolated and purified. By physical and chemical properties, IR, MS (EI-MS, high
      resolution EI-MS), 1D NMR ((1)H NMR, (13)C NMR) and 2D NMR (HSQC, (1)H-(1)H COSY,
      HMBC), their structures were identified as beta-sitosterol (1), stigmasterol (2),
      scopolin (3), 2-hydroxy-1,7,8-trimethoxyanthracene-9,10-dione (4), oleanolic acid
      (5), ursolic acid (6), methyl barbinervate (7), beta-daucosterol (8) and p
      Hydroxybenzoic acid (9). These compounds were isolated from HC for the first
      time, and 4 a new anthraquinone whose biological activities are worth to be
      investigated in future. These compounds may contribute to the HC's
      pharmacological effects on treating diseases, and may be used as candidates for
      control index in establishing the quality control standard of HC. 

PMID- 27027704
TI  - Determination of the minimum alveolar concentration of isoflurane that blunts
      adrenergic responses in sheep and evaluation of the effects of fentanyl.
AB  - OBJECTIVE: To determine the minimum alveolar concentration that blunts adrenergic
      responses (MACBAR) for isoflurane and evaluate effects of fentanyl on isoflurane
      MACBAR in sheep. ANIMALS 13 healthy adult Dorset-cross adult ewes. PROCEDURES: In
      a crossover design, each ewe was anesthetized 2 times for determination of
      isoflurane MACBAR. Anesthesia was induced with propofol administered IV. Sheep
      initially received fentanyl (5 MUg/kg, IV, followed by a constant rate infusion
      of 5 MUg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (control
      treatment). After a washout period of at least 8 days, the other treatment was
      administered. For MACBAR determination, a mechanical nociceptive stimulus (ie,
      sponge forceps) was applied at the coronary band for 1 minute. The MACBAR values
      of the 2 treatments were compared by means of a paired t test. During MACBAR
      determination, blood samples were collected for measurement of plasma fentanyl
      concentration. RESULTS: Mean +/- SD isoflurane MACBAR of the fentanyl and control
      treatments was 1.70 +/- 0.28% and 1.79 +/- 0.35%, respectively; no significant
      difference was found between the 2 treatments. Plasma concentration of fentanyl
      reached a median steady-state concentration of 1.69 ng/mL (interquartile range
      [25th to 75th percentile], 1.47 to 1.79 ng/mL), which was maintained throughout
      the study. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of fentanyl at 5
      MUg/kg, IV, followed by a constant rate infusion of the drug at 5 MUg/kg/h did
      not decrease isoflurane MACBAR. Further studies to determine the effect of higher
      doses of fentanyl on inhalation anesthetic agents and their potential adverse
      effects are warranted.

PMID- 27027706
TI  - Correlation of the ratio of caudal vena cava diameter and aorta diameter with
      systolic pressure variation in anesthetized dogs.
AB  - OBJECTIVE: To evaluate the correlation coefficient of the ratio between diameter
      of the caudal vena cava (CVC) and diameter of the aorta (Ao) in dogs as
      determined ultrasonographically with systolic pressure variation (SPV). ANIMALS:
      14 client-owned dogs (9 females and 5 males; mean +/- SD age, 73 +/- 40 months;
      mean body weight, 22 +/- 7 kg) that underwent anesthesia for repair of skin
      wounds. PROCEDURES: Anesthesia was induced. Controlled mechanical ventilation
      with a peak inspiratory pressure of 8 cm H2O was immediately started, and SPV was
      measured. During a brief period of suspension of ventilation, CVC-to-Ao ratio was
      measured on a transverse right-lateral intercostal ultrasonographic image
      obtained at the level of the porta hepatis. When the SPV was >= 4 mm Hg, at least
      1 bolus (3 to 4 mL/kg) of Hartmann solution was administered IV during a 1-minute
      period. Bolus administration was stopped and the CVC-to-Ao ratio measured when
      SPV was < 4 mm Hg. Correlation coefficient analysis was performed. RESULTS: 28
      measurements were obtained. The correlation coefficient was 0.86 (95% confidence
      interval, 0.72 to 0.93). Mean +/- SD SPV and CVC-to-Ao ratio before bolus
      administration were 7 +/- 2 mm Hg and 0.52 +/- 0.16, respectively. Mean +/- SD
      SPV and CVC-to-Ao ratio after bolus administration were 2 +/- 0.6 mm Hg and 0.91
      +/- 0.13, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, the
      CVC-to-Ao ratio was a feasible, noninvasive ultrasonographically determined value
      that correlated well with SPV.

PMID- 27027705
TI  - Radiographic evaluation of the width of the femorotibial joint space in horses.
AB  - OBJECTIVE: To measure the minimal joint space width (mJSW) in caudocranial
      radiographic views of orthopedically normal femorotibial joints of horses, to
      compare the accuracy of measurements with those of a software program designed
      for humans, and to identify the ideal caudocranial radiographic projection angle
      for mJSW measurement. ANIMALS 12 healthy mares (22 femorotibial joints) and 3
      equine cadavers (6 stifle joints). PROCEDURES: Caudocranial views of femorotibial
      joints were acquired in the proximodistal plane at 5 degrees , 10 degrees , and
      15 degrees  (caudo-5 degrees -proximal-craniodistal oblique, 10 degrees , and 15
      degrees ) and lateromedial plane (caudo-10 degrees -proximo-5 degrees -lateral
      craniodistomedial oblique and caudo-10 degrees -proximo-5 degrees -medial
      craniodistolateral oblique). The mJSWs of medial and lateral femorotibial joint
      compartments were measured manually by 2 evaluators and automatically by a
      digital analysis software program. Interevaluator reproducibility was assessed.
      Post hoc tests were used to identify the projection angle that provided the
      largest measurements. Validation of mJSW measurements was performed by evaluation
      of 6 stifle joints ex vivo. RESULTS: Excellent agreement was achieved between the
      2 evaluators and between the veterinary radiologist and the analysis software for
      the medial and lateral compartments of femorotibial joints. Angle of caudocranial
      view in the proximodistal but not lateromedial plane had a significant effect on
      the medial compartment mJSW measurements. Mean mJSW for the medial compartment
      was significantly higher for the caudoproximal-craniodistal oblique projection
      made at 10 degrees  from the horizontal than for other angles. Angle had no
      significant effect on mean mJSW for the lateral compartment. Agreement between
      automated measurements of mJSW in the medial compartment and thickness of
      nonmineralized cartilage in histologic preparations of associated tissues was
      excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Measurements of mJSW in the medial
      compartment of femorotibial joints, the most common site of osteoarthritis in
      horses, were reproducible and optimal with a caudoproximal-craniodistal oblique
      radiographic projection made at 10 degrees  from the horizontal.

PMID- 27027707
TI  - Effects of contrast medium injection technique on attenuation values of adrenal
      glands in healthy dogs during contrast-enhanced computed tomography.
AB  - OBJECTIVE: To assess the effects of 3 contrast medium injection techniques on
      attenuation values for canine adrenal glands during contrast-enhanced CT.
      ANIMALS: 9 healthy Beagles. PROCEDURES: 3 protocols were evaluated in a
      randomized cross-over design study: 700 mg of iodine/kg at a constant injection
      rate over 20 seconds (full-dose constant rate), the same dose at a rate following
      an exponential decay curve over 20 seconds (full-dose decelerated rate), and 350
      mg of iodine/kg at a constant injection rate over 10 seconds (half-dose constant
      rate). Multislice CT images were obtained before and at predetermined time points
      after the start of contrast medium injection. RESULTS: Median peak attenuation
      values were 129, 133, and 87 Hounsfield units with the full-dose constant rate,
      full-dose decelerated rate, and half-dose constant rate injection protocols,
      respectively. Peak attenuation differed significantly between the full-dose
      constant rate and half-dose constant rate injection protocols and between the
      full-dose decelerated rate and half-dose constant rate injection protocols.
      Median time to peak attenuation did not differ significantly among injection
      methods and was 30, 23, and 15 seconds for the full-dose constant rate, full-dose
      decelerated rate, and half-dose constant rate injections, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: The dose of contrast medium and the timing of
      postinjection CT scanning were main determinants of peak attenuation for adrenal
      glands in healthy dogs; effects of the 3 injection protocols on attenuation were
      minor. The exponentially decelerated injection method was subjectively complex. A
      constant injection protocol delivering 700 mg of iodine/kg over 20 seconds, with
      scans obtained approximately 30 seconds after starting contrast medium injection,
      provided images with maximum adrenal gland attenuation values.

PMID- 27027708
TI  - Serum and tissue concentrations of gallium after oral administration of gallium
      nitrate and gallium maltolate to neonatal calves.
AB  - OBJECTIVE: To determine serum and tissue concentrations of gallium (Ga) after
      oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to
      neonatal calves. ANIMALS: 8 healthy neonatal calves. PROCEDURES: Calves were
      assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered
      as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for
      GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25,
      0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24
      hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after
      Ga administration on day 5. On day 6, calves were euthanized and tissue samples
      were obtained. Serum and tissue Ga concentrations were measured by use of mass
      spectrometry. RESULTS: Data were adjusted for total Ga dose, and comparisons were
      made between the 2 groups. Calves receiving GaM had a significantly higher dose
      adjusted area under the curve and dose-adjusted maximum serum Ga concentration
      than did calves receiving GaN. Despite receiving less Ga per dose, calves
      receiving GaM had tissue Ga concentrations similar to those for calves receiving
      GaN. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, calves receiving GaM had
      significantly higher Ga absorption than did calves receiving GaN. These findings
      suggested that GaM might be useful as a prophylactic agent against Mycobacterium
      avium subsp paratuberculosis infection in neonatal calves.

PMID- 27027709
TI  - In vitro evaluation of mitochondrial dysfunction and treatment with adeno
      associated virus vector in fibroblasts from Doberman Pinschers with dilated
      cardiomyopathy and a pyruvate dehydrogenase kinase 4 mutation.
AB  - OBJECTIVE: To compare mitochondrial oxygen consumption rate (OCR) of fibroblasts
      from Doberman Pinschers with and without dilated cardiomyopathy (DCM) and
      mutation of the gene for pyruvate dehydrogenase kinase isozyme 4 (PDK4) and to
      evaluate in vitro whether treatment with adeno-associated virus (AAV) vector
      (i.e., gene therapy) would alter metabolic efficiency. ANIMALS: 10 Doberman
      Pinschers screened for DCM and PDK4 mutation. PROCEDURES Fibroblasts were
      harvested from skin biopsy specimens obtained from Doberman Pinschers, and dogs
      were classified as without DCM or PDK4 mutation (n = 3) or with occult DCM and
      heterozygous (4) or homozygous (3) for PDK4 mutation. Fibroblasts were or were
      not treated with tyrosine mutant AAV type 2 vector containing PDK4 at
      multiplicities of infection of 1,000. Mitochondrial OCR was measured to evaluate
      mitochondrial metabolism. The OCR was compared among dog groups and between
      untreated and treated fibroblasts within groups. RESULTS: Mean +/- SD basal OCR
      of fibroblasts from heterozygous (74 +/- 8 pmol of O2/min) and homozygous (58 +/-
      12 pmol of O2/min) dogs was significantly lower than that for dogs without PDK4
      mutation (115 +/- 9 pmol of O2/min). After AAV transduction, OCR did not increase
      significantly in any group (mutation-free group, 121 +/- 26 pmol of O2/min;
      heterozygous group, 88 +/- 6 pmol of O2/min; homozygous group, 59 +/- 3 pmol of
      O2/min). CONCLUSIONS AND CLINICAL RELEVANCE: Mitochondrial function was altered
      in skin fibroblasts of Doberman Pinschers with DCM and PDK4 mutation. Change in
      mitochondrial function after in vitro gene therapy at the multiplicities of
      infection used in this study was not significant.

PMID- 27027710
TI  - Diagnostic accuracy of a rapid immunoassay for point of-care detection of urinary
      tract infection in dogs.
AB  - OBJECTIVE: To determine the diagnostic accuracy of a rapid immunoassay (RIA) for
      point-of-care detection of urinary tract infection (UTI) of dogs, compared with
      criterion-referenced diagnosis with bacterial culture. SAMPLE: 200 urine samples
      obtained from dogs and submitted to a veterinary microbiology diagnostic
      laboratory for routine bacterial culture and antimicrobial susceptibility
      determination. PROCEDURES: Samples were evaluated by use of quantitative
      bacterial culture and the RIA. Sensitivity, specificity, and positive and
      negative predictive values of the RIA were calculated; results of bacterial
      culture were the criterion-referenced outcome. A kappa statistic was calculated
      to determine agreement between bacterial culture and RIA results. RESULTS: 56 of
      200 (28%) urine samples had positive results for bacterial growth by use of
      culture methods; there were 38 (19%) positive results likely to be associated
      with bacterial UTI on the basis of sample collection method and bacterial
      concentration. Sensitivity and specificity of the RIA for detecting samples
      likely to be associated with UTI (>= 1,000 CFUs/mL) were 97.4% and 98.8%,
      respectively. The positive and negative predictive values of the RIA for
      bacterial cultures with likely UTI were 0.949 and 0.994, respectively. Agreement
      between bacterial culture and RIA outcome for UTI was substantial (weighted
      kappa, 0.718). CONCLUSIONS AND CLINICAL RELEVANCE: The RIA test evaluated in this
      study accurately detected UTI of dogs, compared with detection with the criterion
      referenced bacterial culture method. Use of this point-of-care RIA could allow
      clinicians to diagnose UTI at the time of a patient visit and provide information
      useful for immediately initiating empirical antimicrobial treatment.

PMID- 27027711
TI  - Quantitative assessment of two methods of tiludronate administration for the
      treatment of lameness caused by navicular syndrome in horses.
AB  - OBJECTIVE: To determine effects of 2 tiludronate administration protocols on
      measures of lameness in horses with navicular syndrome (NS). ANIMALS: 12 horses
      with bilateral forelimb NS. PROCEDURES: Horses were randomly assigned to receive
      tiludronate (1 mg/kg), diluted in 5 L of isotonic electrolyte solution and
      delivered through a jugular vein catheter (systemic treatment group; n = 6), or
      tiludronate (0.1 mg/kg), diluted with saline (0.9% NaCl) solution to a total
      volume of 35 mL and delivered into the lateral digital vein of each forelimb with
      an IV regional limb perfusion (IVRLP) technique (IVRLP group; 6). Mean peak
      vertical ground reaction force (pVGRF) measured with a stationary force plate and
      subjective lameness scores (SLSs) were recorded before (day -1) and at
      predetermined time points after tiludronate administration on day 0. Mean pVGRFs
      (standardized as percentage body weight of force) and mean SLSs for the most lame
      forelimb and for both forelimbs of horses in each group were compared with day -1
      values to determine treatment effect. RESULTS: Mean pVGRF for both forelimbs and
      for the most lame forelimbs of systemically treated horses were significantly
      increased on days 120 and 200, compared with day -1 results. No significant
      difference in mean pVGRF was observed for IVRLP-treated horses. The SLSs were not
      improved at any time point following systemic treatment and were improved only on
      day 120 following IVRLP. CONCLUSIONS AND CLINICAL RELEVANCE: Tiludronate (1
      mg/kg, IV) as a single systemic treatment appeared to be beneficial for horses
      with NS, but no horses were judged as sound during the study period. Additional
      research on IVRLP with tiludronate is needed before this method can be
      recommended.

PMID- 27027712
TI  - In vitro and in vivo assessment of platelet function in healthy dogs during
      administration of a low-dose aspirin regimen.
AB  - OBJECTIVE: To assess the in vitro and in vivo platelet function of healthy dogs
      during administration of a low-dose aspirin regimen. ANIMALS: 16 dogs.
      PROCEDURES: Dogs received aspirin (1 mg/kg, PO, q 24 h) for 7 days. Blood and
      urine samples were collected before (day 1; baseline) and on days 3 and 7 of the
      low-dose aspirin regimen. Platelet function was evaluated by use of turbidimetric
      and conventional impedance aggregometry, multiple-electrode impedance
      aggregometry, a platelet function analyzer (PFA), and determination of urine 11
      dehydro-thromboxane B2 concentration. Turbidimetric aggregometry results were
      compared with the results obtained by the other 4 methods. Fourteen days after
      cessation of aspirin, platelet-rich plasma was incubated with acetylsalicylic
      acid and platelet function was assessed by turbidimetric aggregometry to
      determine whether this technique could accurately identify dogs that responded to
      the low-dose aspirin regimen. RESULTS: Of the 16 dogs, 13 had turbidimetric and
      conventional impedance aggregometry results that were decreased by > 25% from
      baseline on days 3 and 7, and 4 and 7 dogs had PFA closure times > 300 seconds on
      days 3 and 7, respectively. The median urine 11-dehydro-thromboxane B2
      concentration-to-creatinine concentration ratio decreased by 49% between days 1
      and 7. Turbidimetric aggregometry results were correlated with conventional
      impedance aggregometry results. There was poor agreement between the
      turbidimetric aggregometry and PFA results. The multiple-electrode impedance
      aggregometry protocol failed to reliably detect aspirin-induced platelet
      dysfunction. In vitro incubation of platelet-rich plasma with acetylsalicylic
      acid followed by turbidimetric aggregometry did not predict whether dogs
      responded to the low-dose aspirin regimen. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicated that the response to a low-dose aspirin regimen varied among
      healthy dogs.

PMID- 27027713
TI  - Muscle activity and hand motion in veterinarians performing laparoscopic training
      tasks with a box trainer.
AB  - OBJECTIVE: To evaluate muscle activity and hand motion in veterinarians
      performing a standard set of laparoscopic training tasks. SAMPLE: 12
      veterinarians with experience performing laparoscopic procedures. PROCEDURES:
      Participants were asked to perform peg transfer, coordination, precision cutting,
      and suturing tasks in a laparoscopic box trainer. Activity of the right biceps
      brachii, triceps brachii, forearm flexor, forearm extensor, and trapezius muscles
      was analyzed by means of surface electromyography. Right hand movements and wrist
      angle data were registered through the use of a data glove, and risk levels for
      the wrist joint were determined by use of a modified rapid upper limb assessment
      (RULA) method. One-way repeated-measures ANOVA with a Bonferroni post hoc test
      was performed to compare values between tasks. RESULTS: Activity in the biceps
      muscle did not differ significantly among the 4 tasks. Activity in the triceps,
      forearm flexor, and forearm extensor muscles was significantly higher during
      precision cutting than during the coordination task. Activity in the trapezius
      muscle was highest during the suturing task and did not differ significantly
      among the other 3 tasks. The RULA score was unacceptable (score, 3) for the
      coordination, peg transfer, and precision cutting tasks but was acceptable
      (score, 2) for the suturing task. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that the ergonomics of laparoscopic training depended on the tasks
      performed and the design of the instruments used. Precision cutting and suturing
      tasks were associated with the highest muscle activity. Acceptable wrist
      position, as determined with the RULA method, was found with the suturing task,
      which was performed with an axial-handled instrument.

PMID- 27027714
TI  - Adherence of methicillin-resistant Staphylococcus pseudintermedius to suture
      materials commonly used in small animal surgery.
AB  - OBJECTIVE: To evaluate adherence of methicillin-resistant Staphylococcus
      pseudintermedius (MRSP) to 5 suture materials commonly used in small animal
      surgery. SAMPLE: 10 epidemiologically unrelated MRSP isolates (obtained from dogs
      with clinical infections) that had strong biofilm-forming ability and 5 types of
      suture. PROCEDURES: The 5 types of suture evaluated were monofilament
      polyglecaprone 25, monofilament polydioxanone, triclosan-coated (TC)-monofilament
      polydioxanone, braided polyglactin 910, and barbed monofilament polydioxanone.
      Suture segments were incubated in standard suspensions of MRSP for 2 minutes.
      Segments were then placed in tryptone soy broth and incubated overnight. After
      incubation, segments were rinsed with PBS solution and sonicated to dislodge
      adherent bacteria. Resulting suspensions were used to create serial dilutions
      that were plated, incubated overnight, and counted the following day. Bacterial
      adherence to 1 segment of each suture type was assessed by use of scanning
      electron microscopy. RESULTS: There was significantly less adherence of MSRP to
      TC-monofilament polydioxanone than to polyglecaprone 25, polyglactin 910, barbed
      monofilament polydioxanone, and monofilament polydioxanone. There was
      significantly less adherence of MSRP to polyglecaprone than to polyglactin 910.
      CONCLUSIONS AND CLINICAL RELEVANCE: Barbed suture had a bacterial adherence
      profile comparable to that for monofilament suture. Adherence of MRSP was
      greatest for braided polyglactin 910. Use of TC-monofilament polydioxanone can be
      considered for patients that are at high risk of developing surgical site
      infections and for which a surgeon chooses a multifilament suture.

PMID- 27027715
TI  - Effect of granulocyte colony-stimulating factor administration on renal
      regeneration after experimentally induced acute kidney injury in dogs.
AB  - OBJECTIVE: To evaluate the effects of granulocyte colony-stimulating factor
      (GCSF) administration in dogs with experimentally induced acute kidney injury.
      ANIMALS: 6 healthy dogs. PROCEDURES: After induction of kidney injury (day 0)
      with cisplatin (5 mg/kg, IV), the dogs were randomly assigned into 2 groups (n =
      3 dogs/group). Then dogs immediately received GCSF (10 MUg/kg) or 1 mL of saline
      (0.9% NaCl) solution (control group) SC; this treatment was repeated once daily
      for 4 additional days (days 1 through 4). A once-daily CBC (day 0 to 4), serum
      biochemical analysis (day 0 to 3), and urinalysis (day 0 to 3) were performed for
      each dog; samples were collected before administration of cisplatin (day 0) and
      before treatment with GCSF or saline solution (days 1 through 4). After sample
      collection and treatment on day 4, all dogs were euthanized; kidney tissue
      samples underwent histologic evaluation, immunohistochemical analyses, and
      cytokine profiling via reverse transcriptase PCR assay. RESULTS: In the GCSF
      treated group, the histologic evaluation and immunohistochemical analyses of
      kidney tissue revealed less fibrotic change and greater proliferation of renal
      tubular epithelial cells, compared with findings in the control group. The mRNA
      profiles of kidney tissue from the GCSF-treated group indicated lower expression
      of tumor necrosis factor-alpha and tumor growth factor-beta, compared with
      findings in the control group; however, concentrations of factors related to
      renal regeneration were not greater in the GCSF-treated group. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated that GCSF treatment can impede renal
      fibrosis and increase proliferation of renal tubules after experimentally induced
      acute kidney injury in dogs.

PMID- 27027716
TI  - Evaluation of autologous bone marrow-derived mesenchymal stem cells on renal
      regeneration after experimentally induced acute kidney injury in dogs.
AB  - OBJECTIVE: To evaluate the usefulness of autologous bone marrow-derived
      mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with
      experimentally induced acute kidney injury. ANIMALS: 6 healthy dogs. PROCEDURES:
      After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs
      immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 *
      10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical
      analysis, and urinalysis were performed for each dog before administration of
      cisplatin and on days 1 through 4. Glomerular filtration rate was determined for
      all dogs on days -7 and 2; BM-MSC tracking by MRI was performed on BM-MSC-treated
      dogs on days -14 and 4. After sample collection and BM-MSC tracking on day 4, all
      dogs were euthanized; kidney tissue samples underwent histologic evaluation,
      immunohistochemical analysis, and cytokine profiling via reverse transcriptase
      PCR assays. RESULTS: Kidney tissue from both groups had mononuclear inflammatory
      cell infiltration, tubular necrosis, dilated tubules, and glomerular damage.
      However, there was less fibrotic change and increased proliferation of renal
      tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for
      the control dogs. Expressions of tumor necrosis factor-alpha and transforming
      growth factor-beta were lower in the BM-MSC-treated group, compared with findings
      for the control group. Laboratory data revealed no improvement in the renal
      function in BM-MSC-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results of
      this study suggested that autologous BM-MSCs may accelerate renal regeneration
      after experimentally induced acute kidney injury in dogs.

PMID- 27027717
TI  - Assessment of the expression of biomarkers of uremic inflammation in dogs with
      renal disease.
AB  - OBJECTIVE: To assess the expression of inflammatory cytokines and enzymes in
      venous whole blood of dogs with impaired renal function attributable to various
      causes. ANIMALS: 46 dogs with acute kidney injury (AKI), 8 dogs with chronic
      kidney disease (CKD), and 10 healthy dogs. PROCEDURES: Dogs with AKI and CKD were
      prospectively enrolled during 2010 if they met inclusion criteria. Demographic
      and laboratory characteristics were evaluated for each dog, and expression of
      inflammatory cytokines (interleukin [IL]-1alpha, IL-1beta, IL-8, tumor necrosis
      factor [TNF]-alpha, IL-10, and transforming growth factor [TGF]-beta) and enzymes
      (inducible nitric oxide synthase [iNOS] and 5-lipoxygenase [5-LO]) was measured
      in venous whole blood obtained at initial evaluation. RESULTS: Dogs with impaired
      renal function had markedly higher expression of the cytokines IL-1alpha, IL
      1beta, and TGF-beta and the enzyme 5-LO, compared with expression in healthy
      dogs. Additionally, 17 of 46 AKI dogs (but none of the CKD dogs) had higher IL-8
      mRNA expression and 3 of 8 CKD dogs (but only 2/46 AKI dogs) had higher TNF-alpha
      expression, compared with results for healthy dogs. No significant difference
      between renal disease groups was detected for inflammatory markers and laboratory
      variables, degree of azotemia, or cause of impaired renal function. CONCLUSIONS
      AND CLINICAL RELEVANCE: In this study, expression of the cytokines IL-1alpha, IL
      1beta, and TGF-beta and the enzyme 5-LO was clearly increased in dogs with renal
      disease, which suggested that these markers were part of an inflammatory response
      in animals with AKI or CKD.

PMID- 27027718
TI  - All-in-one solid-phase microextraction: Development of a selective solid-phase
      microextraction fiber assembly for the simultaneous and efficient extraction of
      analytes with different polarities.
AB  - In the present work, for the first time, an all-in-one solid-phase
      microextraction technique was developed for the simultaneous and efficient
      extraction of analytes within a vast polarity range. A novel fiber assembly
      composed of two different steel components each coated with different coatings
      (polydimethylsiloxane and polyethylene glycol) in terms of polarity by sol-gel
      technology was employed for the extraction of model compounds of different
      polarity in a single run followed by gas chromatography with mass spectrometry.
      Effective parameters in the extraction step and gas chromatography with mass
      spectrometry analysis were optimized for all model compounds. The detection
      limits of the developed method for model compounds were below 0.2 ng/L. The
      repeatability and reproducibility of the proposed method, explained by relative
      standard deviation, varied between 7.22 and 9.15% and between 7.95 and 14.90 (n =
      5), respectively. Results showed that, under random conditions, compared to
      separate extractions performed by two other differently end-coated components
      that had not been assembled as the final dual fiber, as two individual fibers;
      simultaneous, efficient and relatively selective extraction of all model
      compounds was obtained in a single run by the proposed all-in-one technique.
      Finally, the optimized procedure was applied to extraction and determination of
      the model compounds in spiked water samples. 

PMID- 27027719
TI  - The student safety net: a new angle for early intervention.

PMID- 27027720
TI  - Post-operative cognitive dysfunction at 3 months in adults after non-cardiac
      surgery: a qualitative systematic review.
AB  - BACKGROUND: Post-operative cognitive dysfunction is defined as a decline in
      cognitive functions that occurs after surgery, but different diagnostic criteria
      and incidences have been reported in medical literature. Our aim was to determine
      incidence of post-operative cognitive dysfunction 3 months after non-cardiac
      surgery in adults. METHODS: A systematic review of available evidence was
      performed by PRISMA guidelines. A search was done in May-July 2015 on PubMed,
      EMBASE, CINAHL, LILACS, Scielo, Clinical Trials, and Grey Literature Reports.
      Inclusion criteria were prospective design studies with patients over 18 years
      old, surgery under general or regional anesthesia, follow-up for 3 months, and
      use of a neurocognitive battery for diagnosis. We excluded studies made on
      cardiac or brain surgery patients. Risk of bias was assessed using tools from
      National Heart Lung and Blood Institute. RESULTS: We selected 24 studies. Average
      age was 68 years. Only five studies reported incidence of cognitive decline for a
      non-surgical control group. Median number of tests used was 5 (range 3-13).
      Pooled incidence of post-operative cognitive dysfunction at 3 months was 11.7%
      [95% CI 10.9-12.5] but with several methodological differences between studies.
      Increasing age was the most consistent risk factor identified (seven studies).
      CONCLUSIONS: Post-operative cognitive dysfunction in patients is frequent,
      especially in patients over 60 years old. Limitations include methodological
      differences in studies. Efforts must be made to reach a consensus in definition
      and diagnosis for future research.

PMID- 27027721
TI  - Toluene disruption of the functions of L1 cell adhesion molecule at
      concentrations associated with occupational exposures.
AB  - BACKGROUND: Prenatal toluene exposure can cause neurodevelopmental disabilities
      similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar
      to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite
      outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1
      through lipid rafts. Our objective is to determine if toluene inhibits L1
      mediated NOG and toluene inhibits L1 signaling at concentrations achieved during
      occupational exposure. METHODS: Concentrations of toluene reflective of blood
      concentrations achieved in solvent abusers and occupational settings are used.
      Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are
      plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by
      laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2
      h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2
      activation by L1 in CGN is analyzed by immunoblot. RESULTS: Toluene significantly
      reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene
      significantly reduced L1-mediated ERK1/2 phosphorylation. CONCLUSION: Results
      suggest that toluene inhibits L1-lipid raft interactions at occupationally
      relevant concentrations and may lead to a fetal solvent spectrum disorder similar
      to fetal alcohol spectrum disorder.

PMID- 27027722
TI  - Visual tracking in very preterm infants at 4 mo predicts neurodevelopment at 3 y
      of age.
AB  - BACKGROUND: Typically developing infants track moving objects with eye and head
      movements in a smooth and predictive way at 4 mo of age, but this ability is
      delayed in very preterm infants. We hypothesized that visual tracking ability in
      very preterm infants predicts later neurodevelopment. METHOD: In 67 very preterm
      infants (gestational age<32 wk), eye and head movements were assessed at 4 mo
      corrected age while the infant tracked a moving object. Gaze gain, smooth
      pursuit, head movements, and timing of gaze relative the object were analyzed off
      line. Results of the five subscales included in the Bayley Scales of Infant
      Development (BSID-III) at 3 y of age were evaluated in relation to the visual
      tracking data and to perinatal risk factors. RESULTS: Significant correlations
      were obtained between gaze gain and cognition, receptive and expressive language,
      and fine motor function, respectively, also after controlling for gestational
      age, severe brain damage, retinopathy of prematurity, and bronchopulmonary
      dysplasia. CONCLUSION: This is the first study demonstrating that the basic
      ability to visually track a moving object at 4 mo robustly predicts
      neurodevelopment at 3 y of age in children born very preterm.

PMID- 27027723
TI  - Enhanced cAMP-stimulated protein kinase A activity in human fibrolamellar
      hepatocellular carcinoma.
AB  - BACKGROUND: Fibrolamellar hepatocellular carcinoma (FL-HCC) affects children
      without underlying liver disease. A consistent mutation in FL-HCCs leads to
      fusion of the genes encoding a heat shock protein (DNAJB1) and the catalytic
      subunit of protein kinase A (PRKACA). We sought to characterize the resultant
      chimeric protein and its effects in FL-HCC. METHODS: The expression pattern and
      subcellular localization of protein kinase A (PKA) subunits in FL-HCCs were
      compared to paired normal livers by quantitative polymerase chain reaction
      (qPCR), immunoblotting, and immunofluorescence. PKA activity was measured by
      radioactive kinase assay, and we determined whether the FL-HCC mutation is
      present in other primary liver tumors. RESULTS: The fusion transcript and
      chimeric protein were detected exclusively in FL-HCCs. DNAJB1-PRKACA was
      expressed 10-fold higher than the wild-type PRKACA transcript, resulting in
      overexpression of the mutant protein in tumors. Consequently, FL-HCCs possess
      elevated cAMP-stimulated PKA activity compared to normal livers, despite similar
      Kms between the mutant and wild-type kinases. CONCLUSION: FL-HCCs in children and
      young adults uniquely overexpress DNAJB1-PRKACA, which results in elevated cAMP
      dependent PKA activity. These data suggest that aberrant PKA signaling
      contributes to liver tumorigenesis.

PMID- 27027724
TI  - The novel nonapeptide acein targets angiotensin converting enzyme in the brain
      and induces dopamine release.
AB  - BACKGROUND AND PURPOSE: Using an in-house bioinformatics programme, we identified
      and synthesized a novel nonapeptide, H-Pro-Pro-Thr-Thr-Thr-Lys-Phe-Ala-Ala-OH.
      Here, we have studied its biological activity, in vitro and in vivo, and have
      identified its target in the brain. EXPERIMENTAL APPROACH: The affinity of the
      peptide was characterized using purified whole brain and striatal membranes from
      guinea pigs and rats . Its effect on behaviour in rats following intra-striatal
      injection of the peptide was investigated. A photoaffinity UV cross-linking
      approach combined with subsequent affinity purification of the ligand covalently
      bound to its receptor allowed identification of its target. KEY RESULTS: The
      peptide bound with high affinity to a single class of binding sites, specifically
      localized in the striatum and substantia nigra of brains from guinea pigs and
      rats. When injected within the striatum of rats, the peptide stimulated in vitro
      and in vivo dopamine release and induced dopamine-like motor effects. We purified
      the target of the peptide, a ~151 kDa protein that was identified by MS/MS as
      angiotensin converting enzyme (ACE I). Therefore, we decided to name the peptide
      acein. CONCLUSION AND IMPLICATIONS: The synthetic nonapeptide acein interacted
      with high affinity with brain membrane-bound ACE. This interaction occurs at a
      different site from the active site involved in the well-known peptidase
      activity, without modifying the peptidase activity. Acein, in vitro and in vivo,
      significantly increased stimulated release of dopamine from the brain. These
      results suggest a more important role for brain ACE than initially suspected.

PMID- 27027727
TI  - Preparation and characterization of electrical conductive PVA based materials for
      peripheral nerve tube-guides.
AB  - Peripheral nerve regeneration is a serious clinical problem. Presently, there are
      several nerve tube-guides available in the market, however with some limitations.
      The goal of this work was the development of a biomaterial with high electrical
      conductivity to produce tube-guides for nerve regeneration after neurotmesis
      injuries whenrver an end-to-end suture without tension is not possible. A matrix
      of poly(vinyl alcohol) (PVA) was used loaded with the following electrical
      conductive materials: COOH-functionalized multiwall carbon nanotubes (MWCNTs),
      poly(pyrrole) (PPy), magnesium chloride (MgCl2 ), and silver nitrate (AgNO3 ).
      The tube-guide production was carried out by a freezing/thawing process (physical
      crosslinking) with a final annealing treatment. After producing the tube-guide
      for nerve regeneration, the physicochemical characterization was performed. The
      most interesting results were achieved by loading PVA with 0.05% of PPy or COOH-
      functionalized CNTs. These tubes combined the electrical conductivity of carbon
      nanotubes (CNTs) and PPy with the biocompatibility of PVA matrix, with potential
      clinical application for nerve regeneration. (c) 2016 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 104A: 1981-1987, 2016.

PMID- 27027726
TI  - Dipolar Dyes with a Pyrrolo[2,3-b]quinoxaline Skeleton Containing a Cyano Group
      and a Bridged Tertiary Amino Group: Synthesis, Solvatofluorochromism, and
      Bioimaging.
AB  - Two strongly polarized dipolar chromophores possessing a cyclic tertiary amino
      group at one terminus of the molecule and a CN group at the opposite terminus
      were designed and synthesized. Their rigid skeleton contains the rarely studied
      pyrrolo[2,3-b]quinoxaline ring system. The photophysical properties of these
      regioisomeric dyes were different owing to differing pi conjugation between the
      CN group and the electron-donor moiety. These dipolar molecules showed very
      intense emission, strong solvatofluorochromism, and sufficient two-photon
      brightness for bioimaging. One of these regioisomeric dyes, namely, 11
      carbonitrile-2,3,4,5,6,7-hexahydro-1H-3a,8,13,13b
      tetraazabenzo[b]cyclohepta[1,2,3-jk]fluorene, was successfully utilized in two
      photon imaging of mouse organ tissues and showed distinct tissue morphology with
      high resolution.

PMID- 27027728
TI  - Association between Beta1 -Adrenergic Receptor Polymorphism and Risk of ICD Shock
      in Heart Failure Patients.
AB  - BACKGROUND: Sympathetic activation in heart failure patients favors the
      development of ventricular arrhythmias, thus leading to an increased risk of
      sudden cardiac death. beta1 - and beta2 -adrenergic receptor polymorphisms have
      been linked to the risk of sudden death. Implantable cardioverter-defibrillators
      (ICD) are implanted in a large percentage of heart failure patients, and beyond
      preventing sudden cardiac death they provide a continuous monitoring of major
      ventricular arrhythmias and of their own interventions. We investigated whether
      functionally relevant beta1 - and beta2 -adrenergic receptor polymorphisms are
      associated with risk of ICD shocks, as evidenced in ICD memory. METHODS: 311
      patients with systolic heart failure were enrolled, and number and timing of
      shocks in ICD memory were recorded. Four selected polymorphisms were determined:
      beta1 -adrenergic receptor polymorphisms Ser(49) Gly and Arg(389) Gly and beta2 
      adrenergic receptor polymorphisms Arg(16) Gly and Gln(27) Glu. RESULTS: Only
      Ser(49) Gly was significantly correlated with time free from ICD shocks, both
      considering time to the first event in a Cox model (hazard ratio 2.117), and
      modeling repeated events with the Andersen-Gill method (hazard ratio 2.088). Gly
      allele carriers had a higher probability of ICD shock. The relationship remained
      significant even after adjusting for ejection fraction and beta-blocker dosage
      (hazard ratio 1.910). CONCLUSIONS: Data from our study suggest that the beta
      adrenoreceptor Gly 49 allele of the beta1 -adrenergic receptor Ser(49) Gly
      polymorphisms may increase the risk of ICD shock in patients with heart failure,
      independent of beta-blocker dosage.

PMID- 27027729
TI  - Perception Differences in Ambiguous Forms of Workplace Sexual Harassment: A
      Comparison between the United States and Turkey.
AB  - Certain social-sexual behaviors that could be potentially encountered in
      workplaces are ambiguous in nature and perceiving them as sexual harassment can
      depend on the culture. With an aim to delineate the overlap and distinctions of
      sexual harassment perceptions of such behaviors across samples of women
      university students from Turkey (TR, N = 215) and the United States (US, N =
      209), measurement invariance and latent mean differences in perceiving three
      ambiguous forms; sexist hostility, sexual hostility, and insinuation-of-interest,
      were examined. It was hypothesized that the US sample would perceive sexist
      hostility more sexually harassing as sexist workplace discriminatory practices
      are emphasized as a form of sexual harassment, and that the TR sample would
      perceive sexual hostility and insinuation-of-interest as more sexually harassing
      as women in TR operate in a conservative context. Despite similarities in rank
      ordering, US participants perceived sexist hostility more sexually harassing;
      insinuation-of-interest and sexual hostility less sexually harassing than Turkish
      participants, supporting all three hypotheses. There are implications of
      differing perceptions across cultures for organizations in terms of disseminating
      awareness via training programs about the forms of sexual harassment (SH) in a
      local context and for taking account of local findings in shaping the labor code
      of countries in relation to SH. 

PMID- 27027730
TI  - Reliability of Clinical Assessments in Older Adults With Syncope or Near Syncope.
AB  - OBJECTIVES: Clinical prediction models for risk stratification of older adults
      with syncope or near syncope may improve resource utilization and management.
      Predictors considered for inclusion into such models must be reliable. Our
      primary objective was to evaluate the inter-rater agreement of historical,
      physical examination, and electrocardiogram (ECG) findings in older adults
      undergoing emergency department (ED) evaluation for syncope or near syncope. Our
      secondary objective was to assess the level of agreement between clinicians on
      the patient's overall risk for death or serious cardiac outcomes. METHODS: We
      conducted a cross-sectional study at 11 EDs in adults 60 years of age or older
      who presented with unexplained syncope or near syncope. We excluded patients with
      a presumptive cause of syncope (e.g., seizure) or if they were unable or
      unwilling to follow-up. Evaluations of the patient's past medical history and
      current medication use were completed by treating provider and trained research
      associate pairs. Evaluations of the patient's physical examination and ECG
      interpretation were completed by attending/resident, attending/advanced practice
      provider, or attending/attending pairs. All evaluations were blinded to the
      responses from the other rater. We calculated the percent agreement and kappa
      statistic for binary variables. Inter-rater agreement was considered acceptable
      if the kappa statistic was 0.6 or higher. RESULTS: We obtained paired
      observations from 255 patients; mean (+/-SD) age was 73 (+/-9) years, 137 (54%)
      were male, and 204 (80%) were admitted to the hospital. Acceptable agreement was
      achieved in 18 of the 21 (86%) past medical history and current medication
      findings, none of the 10 physical examination variables, and three of the 13
      (23%) ECG interpretation variables. There was moderate agreement (Spearman
      correlation coefficient, r = 0.40) between clinicians on the patient's
      probability of 30-day death or serious cardiac outcome, although as the
      probability increased, there was less agreement. CONCLUSIONS: Acceptable
      agreement between raters was more commonly achieved with historical rather than
      physical examination or ECG interpretation variables. Clinicians had moderate
      agreement in assessing the patient's overall risk for a serious outcome at 30
      days. Future development of clinical prediction models in older adults with
      syncope should account for variability of assessments between raters and consider
      the use of objective clinical variables.

PMID- 27027731
TI  - Caloric restriction coupled with radiation decreases metastatic burden in triple
      negative breast cancer.
AB  - PURPOSE: Metastatic breast cancer is devastating and triple negative breast
      cancers (TNBC) have a higher propensity for metastasis. Improved local control
      upfront in this aggressive cancer could potentially decrease its propensity
      toward metastasis. We sought to determine if using caloric restriction (CR) as a
      systemic therapy, combined with radiation therapy (IR) to the primary tumor, may
      impact metastatic disease. METHODS: An orthotopic mouse model using a highly
      metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable
      tumors. Mice were then treated with CR, IR, and a combination of the two. In vivo
      imaging was performed for metastatic evaluation. Molecular evaluation of the
      tumors was performed, generating a mechanistic hypothesis for CR, which was then
      tested with pertinent pathway inhibition in the model. RESULTS: CR significantly
      increased the time to developing metastases, decreased the overall number and
      volume of lung metastases, and increased survival. CR decreased proliferation,
      increased apoptosis and globally downregulated the IGF-1R signaling pathway.
      Adding an IGF-1R/INSR inhibitor to local IR in vivo accomplished a decrease in
      metastases similar to CR plus IR, demonstrating the importance of the IGF-1R
      signaling pathway, and underscoring it as a possible mechanism for CR.
      CONCLUSIONS: CR decreased metastatic burden and therefore may complement
      cytotoxic therapies being used in the clinical setting for metastatic disease.
      Downregulation of the IGF-1R pathway, is in part responsible for this response
      and modulating IGF-1R directly resulted in similar improved progression-free
      survival. The novel use of CR has the potential to enhance clinical outcomes for
      patients with metastatic breast cancer.

PMID- 27027732
TI  - Effectiveness of motor interventions in infants with cerebral palsy: a systematic
      review.
AB  - AIM: To systematically review the evidence on the effectiveness of motor
      interventions for infants from birth to 2 years with a diagnosis of cerebral
      palsy or at high risk of it. METHOD: Relevant literature was identified by
      searching journal article databases (PubMed, Embase, CINAHL, Cochrane, Web of
      Knowledge, and PEDro). Selection criteria included infants between the ages of
      birth and 2 years diagnosed with, or at risk of, cerebral palsy who received
      early motor intervention. RESULTS: Thirty-four studies met the inclusion
      criteria, including 10 randomized controlled trials. Studies varied in quality,
      interventions, and participant inclusion criteria. Neurodevelopmental therapy was
      the most common intervention investigated either as the experimental or control
      assignment. The two interventions that had a moderate to large effect on motor
      outcomes (Cohen's effect size>0.7) had the common themes of child-initiated
      movement, environment modification/enrichment, and task-specific training.
      INTERPRETATION: The published evidence for early motor intervention is limited by
      the lack of high-quality trials. There is some promising evidence that early
      intervention incorporating child-initiated movement (based on motor-learning
      principles and task specificity), parental education, and environment
      modification have a positive effect on motor development. Further research is
      crucial.

PMID- 27027733
TI  - The Application of Copper/Iron Cocatalysis in Cross-Coupling Reactions.
AB  - For conventional cross-couplings in organic chemistry, precious metal (such as Pd
      or Rh) complexes have been the preferable choices as catalysts. However, their
      high cost, toxicity, and potential contamination of products limit their massive
      applications on some occasions, particularly in the pharmaceutical industry,
      where close monitoring of the metal contamination of products is required.
      Therefore, the use of metals that are less expensive and less toxic than Pd or Rh
      can be greatly advantageous and earth abundant metal (such Fe or Cu) catalysts
      have shown promise for replacing the precious metals. Interestingly, a certain
      copper catalyst combined with an iron catalyst displays higher catalytic
      efficiency than itself in various coupling reactions. Notably, ligand-free
      conditions make such protocols more useful and practical in many cases. In this
      account, we summarize the recent progress made in this increasingly attractive
      topic by describing successful examples, including our own work in the
      literature, regarding effective copper/iron cocatalysis. In addition, a few
      examples involving a magnetic and readily recyclable CuFe2 O4 nanoparticle
      cocatalyst are also included.

PMID- 27027734
TI  - Patterns of impaired oral health-related quality of life dimensions.
AB  - How dental patients are affected by oral conditions can be described with the
      concept of oral health-related quality of life (OHRQoL). This concept intends to
      make the patient experience measurable. OHRQoL is multidimensional, and Oral
      Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact were
      suggested as its four dimensions and consequently four scores are needed for
      comprehensive OHRQoL assessment. When only the presence of dimensional impact is
      measured, a pattern of affected OHRQoL dimensions would describe in a simple way
      how oral conditions influence the individual. By determining which patterns of
      impact on OHRQoL dimensions exist in prosthodontic patients and general
      population subjects, we aimed to identify in which combinations oral conditions'
      functional, painful, aesthetical and psychosocial impact occurs. Data came from
      the Dimensions of OHRQoL Project with Oral Health Impact Profile (OHIP)-49 data
      from 6349 general population subjects and 2999 prosthodontic patients in the
      Learning Sample (N = 5173) and the Validation Sample (N = 5022). We hypothesised
      that all 16 patterns of OHRQoL dimensions should occur in these individuals who
      suffered mainly from tooth loss, its causes and consequences. A dimension was
      considered impaired when at least one item in the dimension was affected
      frequently. The 16 possible patterns of impaired OHRQoL dimensions were found in
      patients and general population subjects in both Learning and Validation Samples.
      In a four-dimensional OHRQoL model consisting Oral Function, Oro-facial Pain, Oro
      facial Appearance and Psychosocial Impact, oral conditions' impact can occur in
      any combination of the OHRQoL dimensions. 

PMID- 27027735
TI  - The insulinotropic effect of exogenous glucagon-like peptide-1 is not affected by
      acute vagotomy in anaesthetized pigs.
AB  - What is the central question of this study? We investigated whether intestinal
      vagal afferents are necessary for the insulinotropic effect of glucagon-like
      peptide-1 (GLP-1) infused into a mesenteric artery or a peripheral vein before
      and after acute truncal vagotomy. What is the main finding and its importance? We
      found no effect of truncal vagotomy on the insulinotropic effect of exogenous GLP
      1 and speculate that high circulating concentrations of GLP-1 after i.v. and i.a.
      infusion might have overshadowed any neural signalling component. We propose that
      further investigations into the possible vagal afferent signalling of GLP-1 would
      best be pursued using enteral stimuli to provide high subepithelial levels of
      endogenous GLP-1. Glucagon-like peptide 1 (GLP-1) is secreted from the gut in
      response to luminal stimuli and stimulates insulin secretion in a glucose
      dependent manner. As a result of rapid enzymatic degradation of GLP-1 by
      dipeptidyl peptidase-4, a signalling pathway involving activation of intestinal
      vagal afferents has been proposed. We conducted two series of experiments in
      alpha-chloralose-anaesthetized pigs. In protocol I, pigs (n = 14) were allocated
      for either i.v. or i.a. (mesenteric) GLP-1 infusions (1 and 2 pmol kg(-1)  min(
      1) , 30 min) while maintaining permissive glucose concentrations at 6 mmol l(-1)
      by i.v. glucose infusion. The GLP-1 infusions were repeated after acute truncal
      vagotomy. In protocol II, pigs (n = 27) were allocated into six groups. Glucagon
      like peptide 1 was infused i.v. or i.a. (mesenteric) for 1 h at 3 or 30 pmol kg(
      1)  min(-1) . During the steady state (21 min into the GLP-1 infusion), glucose
      (0.2 g kg(-1) , i.v.) was administered over 9 min to stimulate beta-cell
      secretion. Thirty minutes after the glucose infusion, GLP-1 infusions were
      discontinued. Following a washout period, the vagal trunks were severed in four
      of six groups (vagal trunks were left intact in two of six groups), whereupon all
      infusions were repeated. We found no effect of vagotomy on insulin or glucagon
      secretion during administration of exogenous GLP-1 in any experiment. We
      speculate that the effect of exogenous GLP-1 overshadowed any effect occurring
      via the vagus. Within dosage groups, total GLP-1 concentrations were similar, but
      intact GLP-1 concentrations were much lower when infused via the mesenteric
      artery because of extensive degradation of GLP-1 in the splanchnic bed. This
      demonstrates the effectiveness with which intestinal capillary dipeptidyl
      peptidase-4 protects the systemic circulation from intact GLP-1, consistent with
      a local role for GLP-1 involving activation of vagal pathways.

PMID- 27027736
TI  - Renal ablation using magnetic resonance-guided high intensity focused ultrasound:
      Magnetic resonance imaging and histopathology assessment.
AB  - AIM: To use magnetic resonance-guided high intensity focused ultrasound (MRg
      HIFU), magnetic resonance imaging (MRI) and histopathology for noninvasively
      ablating, quantifying and characterizing ablated renal tissue. METHODS: Six
      anesthetized/mechanically-ventilated pigs underwent single/double renal
      sonication (n = 24) using a 3T-MRg-HIFU (1.1 MHz frequency and 3000J-4400J
      energies). T2-weighted fast spin echo (T2-W), perfusion saturation recovery
      gradient echo and contrast enhanced (CE) T1-weighted (T1-W) sequences were used
      for treatment planning, temperature monitoring, lesion visualization,
      characterization and quantification, respectively. Histopathology was conducted
      in excised kidneys to quantify and characterize cellular and vascular changes.
      Paired Student's t-test was used and a P-value < 0.05 was considered
      statistically significant. RESULTS: Ablated renal parenchyma could not be
      differentiated from normal parenchyma on T2-W or non-CE T1-W sequences. Ablated
      renal lesions were visible as hypoenhanced regions on perfusion and CE T1-W MRI
      sequences, suggesting perfusion deficits and necrosis. Volumes of ablated
      parenchyma on CE T1-W images in vivo (0.12-0.36 cm(3) for single sonication
      3000J, 0.50-0.84 cm(3), for double 3000J, 0.75-0.78 cm(3) for single 4400J and
      0.12-2.65 cm(3) for double 4400J) and at postmortem (0.23-0.52 cm(3), 0.25-0.82
      cm(3), 0.45-0.68 cm(3) and 0.29-1.80 cm(3), respectively) were comparable. The
      ablated volumes on 3000J and 4400J double sonication were significantly larger
      than single (P < 0.01), thus, the volume and depth of ablated tissue depends on
      the applied energy and number of sonication. Macroscopic and microscopic
      examinations confirmed the locations and presence of coagulation necrosis,
      vascular damage and interstitial hemorrhage, respectively. CONCLUSION: Contrast
      enhanced MRI provides assessment of MRg-HIFU renal ablation. Histopathology
      demonstrated coagulation necrosis, vascular damage and confirmed the volume of
      damage seen on MRI.

PMID- 27027737
TI  - Parallel genetic divergence among coastal-marine ecotype pairs of European
      anchovy explained by differential introgression after secondary contact.
AB  - Ecophenotypic differentiation among replicate ecotype pairs within a species
      complex is often attributed to independent outcomes of parallel divergence driven
      by adaptation to similar environmental contrasts. However, the extent to which
      parallel phenotypic and genetic divergence patterns have emerged independently is
      increasingly questioned by population genomic studies. Here, we document the
      extent of genetic differentiation within and among two geographic replicates of
      the coastal and marine ecotypes of the European anchovy (Engraulis encrasicolus)
      gathered from Atlantic and Mediterranean locations. Using a genome-wide data set
      of RAD-derived SNPs, we show that habitat type (marine vs. coastal) is the most
      important component of genetic differentiation among populations of anchovy. By
      analysing the joint allele frequency spectrum of each coastal-marine ecotype
      pair, we show that genomic divergence patterns between ecotypes can be explained
      by a postglacial secondary contact following a long period of allopatric
      isolation (c. 300 kyrs). We found strong support for a model including
      heterogeneous migration among loci, suggesting that secondary gene flow has
      eroded past differentiation at different rates across the genome. Markers
      experiencing reduced introgression exhibited strongly correlated differentiation
      levels among Atlantic and Mediterranean regions. These results support that
      partial reproductive isolation and parallel genetic differentiation among
      replicate pairs of anchovy ecotypes are largely due to a common divergence
      history prior to secondary contact. They moreover provide comprehensive insights
      into the origin of a surprisingly strong fine-scale genetic structuring in a high
      gene flow marine fish, which should improve stock management and conservation
      actions. 

PMID- 27027738
TI  - Toads on Lava: Spatial Ecology and Habitat Use of Invasive Cane Toads (Rhinella
      marina) in Hawai'i.
AB  - Most ecological research on cane toads (Rhinella marina) has focused on invasive
      populations in Australia, ignoring other areas where toads have been introduced.
      We radio-tracked and spool-tracked 40 toads, from four populations on the island
      of Hawai'i. Toads moved extensively at night (mean 116 m, from spool-tracking)
      but returned to the same or a nearby retreat-site each day (from radio-tracking,
      mean distance between successive retreat sites 11 m; 0 m for 70% of records).
      Males followed straighter paths during nocturnal movements than did females.
      Because moist sites are scarce on the highly porous lava substrate, Hawai'ian
      toads depend on anthropogenic disturbance for shelter (e.g. beneath buildings),
      foraging (e.g. suburban lawns, golf courses) and breeding (artificial ponds).
      Foraging sites are further concentrated by a scarcity of flying insects (negating
      artificial lights as prey-attractors). Habitat use of toads shifted with time (at
      night, toads selected areas with less bare ground, canopy, understory and leaf
      litter), and differed between sexes (females foraged in areas of bare ground with
      dense understory vegetation). Cane toads in Hawai'i thrive in scattered moist
      patches within a severely arid matrix, despite a scarcity of flying insects,
      testifying to the species' ability to exploit anthropogenic disturbance. 

PMID- 27027739
TI  - In reference to Is the OSA-18 predictive of obstructive sleep apnea: Comparison
      to polysomnography.

PMID- 27027740
TI  - Design of Novel Relaxase Substrates Based on Rolling Circle Replicases for
      Bioconjugation to DNA Nanostructures.
AB  - During bacterial conjugation and rolling circle replication, HUH endonucleases,
      respectively known as relaxases and replicases, form a covalent bond with ssDNA
      when they cleave their target sequence (nic site). Both protein families show
      structural similarity but limited amino acid identity. Moreover, the organization
      of the inverted repeat (IR) and the loop that shape the nic site differs in both
      proteins. Arguably, replicases cleave their target site more efficiently, while
      relaxases exert more biochemical control over the process. Here we show that
      engineering a relaxase target by mimicking the replicase target, results in
      enhanced formation of protein-DNA covalent complexes. Three widely different
      relaxases, which belong to MOBF, MOBQ and MOBP families, can properly cleave DNA
      sequences with permuted target sequences. Collaterally, the secondary structure
      that the permuted targets acquired within a supercoiled plasmid DNA resulted in
      poor conjugation frequencies underlying the importance of relaxase accessory
      proteins in conjugative DNA processing. Our results reveal that relaxase and
      replicase targets can be interchangeable in vitro. The new Rep substrates provide
      new bioconjugation tools for the design of sophisticated DNA-protein
      nanostructures. 

PMID- 27027741
TI  - Annular erythematous eruption with a high response to mosquito bite.

PMID- 27027742
TI  - Relative Stereochemistry and Absolute Configuration of Farinosin, a Eudesmanolide
      From Encelia farinosa.
AB  - The naturally occurring eudesmanolide farinosin () is now fully characterized for
      the first time despite its original isolation almost half a century ago. The
      early assumed relative stereochemistry and absolute configuration were confirmed
      by vibrational circular dichroism together with evaluation of the Hooft X-ray
      parameters. The molecular conformation is very similar in the gas stage and in
      the solid state. Chirality 28:415-419, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27027744
TI  - [Kinderdermatologie: ein Kleinod unseres Fachgebiets].

PMID- 27027743
TI  - Trends from 2002 to 2010 in Daily Breakfast Consumption and its Socio-Demographic
      Correlates in Adolescents across 31 Countries Participating in the HBSC Study.
AB  - Breakfast is often considered the most important meal of the day and children and
      adolescents can benefit from breakfast consumption in several ways. The purpose
      of the present study was to describe trends in daily breakfast consumption (DBC)
      among adolescents across 31 countries participating in the HBSC survey between
      2002 to 2010 and to identify socio-demographic (gender, family affluence and
      family structure) correlates of DBC. Cross-sectional surveys including nationally
      representative samples of 11-15 year olds (n = 455,391). Multilevel logistic
      regression analyses modeled DBC over time after adjusting for family affluence,
      family structure and year of survey. In all countries, children in two-parent
      families were more likely to report DBC compared to single parent families. In
      most countries (n = 19), DBC was associated with family affluence. Six countries
      showed an increase in DBC (Canada, Netherland, Macedonia, Scotland, Wales,
      England) from 2002. A significant decrease in DBC from 2002 was found in 11
      countries (Belgium Fr, France, Germany, Croatia, Spain, Poland, Russian
      Federation, Ukraine, Latvia, Lithuania and Norway), while in 5 countries
      (Portugal, Denmark, Finland, Ireland, Sweden) no significant changes were seen.
      Frequency of DBC among adolescents in European countries and North America showed
      a more uniform pattern in 2010 as compared to patterns in 2002. DBC increased
      significantly in only six out of 19 countries from 2002 to 2010. There is need
      for continued education and campaigns to motivate adolescents to consume DBC.
      Comparing patterns across HBSC countries can make an important contribution to
      understanding regional /global trends and to monitoring strategies and
      development of health promotion programs. 

PMID- 27027745
TI  - Proctology - diseases of the anal region.
AB  - Proctology is a medical subspecialty that encompasses diseases of the perianal
      region, anal canal, and rectum. Dermatologists play a pivotal role in this realm,
      as inflammatory perianal disorders, infectious and sexually transmitted diseases,
      as well as perianal tumors and their precursor lesions fall within the core
      competency of dermatology. In a concise manner, the present article highlights
      all relevant disease groups in the field of proctology. With a particular focus
      on aspects pertinent to dermatologists, this includes inflammatory disorders,
      "classic" proctologic diseases, sexually transmitted diseases, malignancies of
      the anal region, as well as pathogen-induced diseases. Despite the wide variety
      of disorders, there are only five key symptoms prompting patients to consult a
      proctologist, including anal pruritus and burning, discharge, bleeding, pain, and
      foreign body sensation. A simple algorithm, which incorporates these symptoms as
      well as key clinical features, may assist in quickly establishing the correct
      diagnosis in everyday clinical practice. 

PMID- 27027748
TI  - Histologic features of granulomatous skin diseases.
AB  - Granulomatous disorders affecting the skin belong to a heterogeneous group of
      diseases, which were predominantly classified based on pathogenetic features. In
      infections diseases a granuloma is formed if an agent could not be eliminated by
      the immune system. Typical agents which cause granulomatous reactions are
      mycobacteria, fungal infections, especially extra European agent, which could
      effect the skin by, dissemination (e.g. histoplasmosis) or parasites, like
      leishmaniasis. 

PMID- 27027749
TI  - Back to the roots - dermatology in ancient Egyptian medicine.
AB  - Although ancient Greek and Roman medicine is generally considered the origin of
      European medicine, there is evidence in ancient Egyptian texts suggesting a
      precursor role of ancient Egyptian medicine in this regard. What did Greek and
      Roman physicians learn from their Egyptian counterparts? Of the medical papyri
      discovered to date, the largest and most significant - the Ebers papyrus and the
      Smith papyrus - originate from the beginning of the New Kingdom, however, they
      were - at least in part - already written during the Old Kingdom. Considering the
      times, the spectrum of diseases treated as well as the range of conservative and
      surgical treatment methods was truly astounding. Taking a medical history,
      performing a thorough manual examination, and assessing clinical findings
      constituted key components in establishing a diagnosis. Apart from hygienic
      aspects, skin and hair disorders, the treatment of acute and chronic wounds and
      injuries as well as cosmetic procedures took on an important role. Even back
      then, physicians sought to assess inflammatory processes with respect to their
      cardinal features, implement graded wound therapy, and treat diseases with
      allopathic drugs. The 'channel theory' prevalent at that time, in which the
      unimpeded flow of bodily fluids was considered a fundamental prerequisite for
      health, may likely be regarded as precursor of ancient Greek humoral pathology.
      The latter became the basis for the subsequently established theory of the four
      humors, and was thus essential for the entire field of medieval medicine. 

PMID- 27027755
TI  - A case of localized, unilateral hyperkeratosis lenticularis perstans on a woman's
      breast.

PMID- 27027752
TI  - Psychosocial burden and desire for support in outpatients with skin cancer.
AB  - BACKGROUND: An important basis for adequate psycho-oncological and psychosocial
      care of cancer patients is the regular assessment of their psychosocial distress
      and thus their need for care. For this purpose, there are numerous questionnaires
      available. The objective of the present study was to assess whether distressed
      patients require professional support and which screening instrument outpatients
      with skin cancer prefer. PATIENTS AND METHODS: In a cross-sectional survey, we
      asked outpatients with skin cancer to fill out three questionnaires assessing
      psychosocial stress, and to indicate which one they considered most adequate.
      Patients were offered the following three instruments: Hornheide Questionnaire
      (27 items), Hornheide Screening Instrument (7 items), and the Distress
      Thermometer. In addition, we inquired about the patients' desire for support.
      RESULTS: (1) Comparing subjective distress and patients' declared desire for
      support revealed a marked divergence. While one-third of the 137 patients were
      identified as being in need of care, only 11.5% of the sample requested such
      support. (2) 63.7% of patients chose the long version of the Hornheide
      Questionnaire. CONCLUSIONS: In addition to their psychosocial burden, patients'
      desire for support should be assessed. Moreover, apart from screening tools,
      other ways to provide access to psychosocial care should be considered.

PMID- 27027757
TI  - Primary cutaneous diffuse large B-cell lymphoma of the face.

PMID- 27027759
TI  - Acne inversa-like skin lesions as a potential adverse event during vemurafenib
      therapy.

PMID- 27027760
TI  - Metastatic Crohn's disease in childhood.

PMID- 27027763
TI  - The comet flap: an alternative technique for the reconstruction of facial
      defects.

PMID- 27027766
TI  - 1st Science Days of the Austrian Society of Dermatology and Venereology (OGDV
      Forschungstage).

PMID- 27027767
TI  - [Tagesnotizen].

PMID- 27027768
TI  - [Laudationes].

PMID- 27027769
TI  - [Nachrufe].

PMID- 27027771
TI  - Improved PCR-Based Detection of Soil Transmitted Helminth Infections Using a Next
      Generation Sequencing Approach to Assay Design.
AB  - BACKGROUND: The soil transmitted helminths are a group of parasitic worms
      responsible for extensive morbidity in many of the world's most economically
      depressed locations. With growing emphasis on disease mapping and eradication,
      the availability of accurate and cost-effective diagnostic measures is of
      paramount importance to global control and elimination efforts. While real-time
      PCR-based molecular detection assays have shown great promise, to date, these
      assays have utilized sub-optimal targets. By performing next-generation
      sequencing-based repeat analyses, we have identified high copy-number, non-coding
      DNA sequences from a series of soil transmitted pathogens. We have used these
      repetitive DNA elements as targets in the development of novel, multi-parallel,
      PCR-based diagnostic assays. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing next
      generation sequencing and the Galaxy-based RepeatExplorer web server, we
      performed repeat DNA analysis on five species of soil transmitted helminths
      (Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Ascaris
      lumbricoides, and Strongyloides stercoralis). Employing high copy-number, non
      coding repeat DNA sequences as targets, novel real-time PCR assays were designed,
      and assays were tested against established molecular detection methods. Each
      assay provided consistent detection of genomic DNA at quantities of 2 fg or less,
      demonstrated species-specificity, and showed an improved limit of detection over
      the existing, proven PCR-based assay. CONCLUSIONS/SIGNIFICANCE: The utilization
      of next-generation sequencing-based repeat DNA analysis methodologies for the
      identification of molecular diagnostic targets has the ability to improve assay
      species-specificity and limits of detection. By exploiting such high copy-number
      repeat sequences, the assays described here will facilitate soil transmitted
      helminth diagnostic efforts. We recommend similar analyses when designing PCR
      based diagnostic tests for the detection of other eukaryotic pathogens.

PMID- 27027772
TI  - gsdf is a downstream gene of dmrt1 that functions in the male sex determination
      pathway of the Nile tilapia.
AB  - Gonadal soma-derived factor (gsdf) is critical for testicular differentiation in
      teleosts, yet detailed analysis of Gsdf on testicular differentiation is lacking.
      In the present study, we knocked out tilapia gsdf using CRISPR/Cas9. F0 gsdf
      deficient XY fish with high mutation rate (>=58%) developed as intersex, with
      ovotestes 90 days after hatching (dah), and become completely sex-reversed with
      ovaries at 180 and 240 dah. Those individuals with a low mutation rate (<58%) and
      XY gsdf(+/-) fish developed as males with normal testes. In F2 XY gsdf(-/-) fish,
      the gonads first expressed Dmrt1, which initiated the male pathway at 10 dah,
      then both male and female pathways were activated, as reflected by the
      simultaneous expression of Dmrt1 and Cyp19a1a in different cell populations at 18
      dah, shifted to the female pathway expressing only Cyp19a1a at 36 dah, and
      finally developed into functional ovaries as adults. The male pathway and Dmrt1
      expression was initiated, but failed to be maintained, in the absence of Gsdf.
      Aromatase-inhibitor treatment from 10 to 35 dah, however, rescued the phenotype,
      resulting in XY gsdf(-/-) with normal testes that expressed Dmrt1 and Cyp11b2. In
      vitro promoter analyses demonstrated that Dmrt1 activated gsdf expression in a
      dose-dependent manner in the presence of Sf1, even though Dmrt1 alone could not.
      Taken together, our results demonstrated that gsdf is a downstream gene of dmrt1.
      Gsdf probably inhibits estrogen production to trigger testicular differentiation.
      Mol. Reprod. Dev. 83: 497-508, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27027773
TI  - Pseudo-Pericardial Tamponade From Right Ventricular Hematoma After Chronic Total
      Occlusion Percutaneous Coronary Intervention of the Right Coronary Artery:
      Successfully Managed Percutaneously With Computerized Tomographic Guided
      Drainage.
AB  - This is the first case reported in the literature of regional tamponade
      physiology following chronic total occlusion (CTO) percutaneous coronary
      intervention (PCI) of the right coronary artery (RCA) with compression of the
      right sided chambers that was managed percutaneously with computerized
      tomographic (CT) guided drainage. This case report highlights the heightened
      index of suspicion needed to make the diagnosis; the often nondiagnostic nature
      of the surface echocardiogram and the need for cross specialty collaboration to
      treat this entity successfully. KEY WORDS: Coronary
      Aneurysm/Dissection/Perforation (CORD); Percutaneous Coronary Intervention (PCI);
      CTO; ICT - Imaging; electron beam CT/multidetector CT (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27027774
TI  - Books on Prescription - community-based health initiative to increase access to
      mental health treatment: an evaluation.
AB  - OBJECTIVE: To evaluate the implementation of a regional Books on Prescription
      (BoP) programme. METHODS: Seven data collection pathways were used to provide
      indicators of program implementation, utilisation, acceptability and reach.
      RESULTS: BoP is seen by prescribers, librarians and consumers as a valuable
      mental health resource. Key areas for improvement were identified: booklist
      literacy level and breadth of topic area; confidentiality; program promotion; and
      prescriber/librarian training. CONCLUSIONS: Recommendations are made regarding
      the improvement of programme acceptability, accessibility and assessment.
      IMPLICATIONS: The establishment of a national BoP scheme would facilitate
      sustainable and consistent methods for BoP promotion and assessment. The authors
      hope this evaluation is a step towards actualising this goal.

PMID- 27027775
TI  - Characterization and Correction of Geometric Distortions in 814 Diffusion
      Weighted Images.
AB  - INTRODUCTION: Diffusion Weighted Imaging (DWI), which is based on Echo Planar
      Imaging (EPI) protocols, is becoming increasingly important for neurosurgical
      applications. However, its use in this context is limited in part by significant
      spatial distortion inherent to EPI. METHOD: We evaluated an efficient algorithm
      for EPI distortion correction (EPIC) across 814 DWI scans from 250 brain tumor
      patients and quantified the magnitude of geometric distortion for whole brain and
      multiple brain regions. RESULTS: Evaluation of the algorithm's performance
      revealed significantly higher mutual information between T1-weighted pre-contrast
      images and corrected b = 0 images than the uncorrected b = 0 images (p < 0.001).
      The distortion magnitude across all voxels revealed a median EPI distortion
      effect of 2.1 mm, ranging from 1.2 mm to 5.9 mm, the 5th and 95th percentile,
      respectively. Regions adjacent to bone-air interfaces, such as the orbitofrontal
      cortex, temporal poles, and brain stem, were the regions most severely affected
      by DWI distortion. CONCLUSION: Using EPIC to estimate the degree of distortion in
      814 DWI brain tumor images enabled the creation of a topographic atlas of DWI
      distortion across the brain. The degree of displacement of tumors boundaries in
      uncorrected images is severe but can be corrected for using EPIC. Our results
      support the use of distortion correction to ensure accurate and careful
      application of DWI to neurosurgical practice.

PMID- 27027776
TI  - Oceanic oxygenation events in the anoxic Ediacaran ocean.
AB  - The ocean-atmosphere system is typically envisioned to have gone through a
      unidirectional oxygenation with significant oxygen increases in the earliest (ca.
      635 Ma), middle (ca. 580 Ma), or late (ca. 560 Ma) Ediacaran Period. However,
      temporally discontinuous geochemical data and the patchy metazoan fossil record
      have been inadequate to chart the details of Ediacaran ocean oxygenation, raising
      fundamental debates about the timing of ocean oxygenation, its purported
      unidirectional rise, and its causal relationship, if any, with the evolution of
      early animal life. To better understand the Ediacaran ocean redox evolution, we
      have conducted a multi-proxy paleoredox study of a relatively continuous, deep
      water section in South China that was paleogeographically connected with the open
      ocean. Iron speciation and pyrite morphology indicate locally euxinic (anoxic and
      sulfidic) environments throughout the Ediacaran in this section. In the same
      rocks, redox sensitive element enrichments and sulfur isotope data provide
      evidence for multiple oceanic oxygenation events (OOEs) in a predominantly anoxic
      global Ediacaran-early Cambrian ocean. This dynamic redox landscape contrasts
      with a recent view of a redox-static Ediacaran ocean without significant change
      in oxygen content. The duration of the Ediacaran OOEs may be comparable to those
      of the oceanic anoxic events (OAEs) in otherwise well-oxygenated Phanerozoic
      oceans. Anoxic events caused mass extinctions followed by fast recovery in
      biologically diversified Phanerozoic oceans. In contrast, oxygenation events in
      otherwise ecologically monotonous anoxic Ediacaran-early Cambrian oceans may have
      stimulated biotic innovations followed by prolonged evolutionary stasis.

PMID- 27027777
TI  - Increased mortality in a Danish cohort of young people with Type 1 diabetes
      mellitus followed for 24 years.
AB  - AIM: To determine the mortality rate in a Danish cohort of children and
      adolescents diagnosed with Type 1 diabetes mellitus compared with the general
      population. METHODS: In 1987 and 1989 we included 884 children and 1020
      adolescents aged 20 years and under, corresponding to 75% of all Danish children
      and adolescents with Type 1 diabetes, in two nationwide studies in Denmark. Those
      who had participated in both investigations (n = 720) were followed until 1
      January 2014, using the Danish Civil Registration System on death certificates
      and emigration. We derived the expected number of deaths in the cohort, using
      population data values from Statistics Denmark to calculate the standardized
      mortality ratio. Survival analysis was performed using Cox proportional hazards
      model. RESULTS: During the 24 years of follow-up, 49 (6.8%) patients died,
      resulting in a standardized mortality ratio of 4.8 (95% confidence interval 3.5,
      6.2) compared with the age-standardized general population. A 1% increase in
      baseline HbA1c (1989), available in 718 of 720 patients, was associated with all
      cause mortality (hazard ratio = 1.38; 95% confidence interval 1.2, 1.6; P <
      0.0001). Type 1 diabetes with multiple complications was the most common reported
      cause of death (36.7%). CONCLUSION: We found an increased mortality rate in this
      cohort of children and adolescents with Type 1 diabetes compared with the general
      population. The only predictor for increased risk of death up to 24 years after
      inclusion was the HbA1c level in 1989. This emphasizes the importance of
      achieving optimal metabolic control in young people with Type 1 diabetes.

PMID- 27027778
TI  - Stereoselective Formation of Fully Substituted Ketone Enolates.
AB  - The application of stereochemically defined acyclic fully substituted enolates of
      ketones to the enantioselective synthesis of quaternary carbon stereocenters
      would be highly valuable. Herein, we describe an approach leading to the
      formation of several new stereogenic centers through a combined metalation
      addition of a carbonyl-carbamoyl transfer to reveal in situ stereodefined
      alpha,alpha-disubstituted enolates of ketone as a single stereoisomer. This
      approach could produce a series of aldol and Mannich products from enol carbamate
      with excellent diastereomeric ratios.

PMID- 27027779
TI  - Morphological analysis of the hagfish heart. II. The venous pole and the
      pericardium.
AB  - The morphological characteristics of the venous pole and pericardium of the heart
      were examined in three hagfish species, Myxine glutinosa, Eptatretus stoutii, and
      Eptatretus cirrhatus. In these species, the atrioventricular (AV) canal is long,
      funnel-shaped and contains small amounts of myocardium. The AV valve is formed by
      two pocket-like leaflets that lack a papillary system. The atrial wall is formed
      by interconnected muscle trabeculae and a well-defined collagenous system. The
      sinus venosus (SV) shows a collagenous wall and is connected to the left side of
      the atrium. An abrupt collagen-muscle boundary marks the SV-atrium transition. It
      is hypothesized that the SV is not homologous to that of other vertebrates which
      could have important implications for understanding heart evolution. In M.
      glutinosa and E. stoutii, the pericardium is a closed bag that hangs from the
      tissues dorsal to the heart and encloses both the heart and the ventral aorta. In
      contrast, the pericardium is continuous with the loose periaortic tissue in E.
      cirrhatus. In all three species, the pericardium ends at the level of the SV
      excluding most of the atrium from the pericardial cavity. In M. glutinosa and E.
      stoutii, connective bridges extend between the base of the aorta and the
      ventricular wall. In E. cirrhatus, the connections between the periaortic tissue
      and the ventricle may carry blood vessels that reach the ventricular base. A
      further difference specific to E. cirrhatus is that the adipose tissue associated
      with the pericardium contains thyroid follicles. J. Morphol. 277:853-865, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27027780
TI  - The HepaRG cell line, a superior in vitro model to L-02, HepG2 and hiHeps cell
      lines for assessing drug-induced liver injury.
AB  - Drug-induced liver injury (DILI) is a leading cause of discontinuation of new
      drug approval or withdrawal of marketed medicine based on safety due to organ
      vulnerability. The aim of this research is to investigate the potential abilities
      of four different in vitro cell models (L-02, HepG2, HepaRG, and hiHeps cell
      lines) in assessing marketed drugs labeled with apparently different types of
      liver injury. A total of 17 drugs with versatile pharmacological profiles were
      chosen, of which, 14 drugs are recognized as DILI agents and 3 drugs are DILI
      irrelevant. Preliminary cellular screening assays indicated that the HepaRG cell
      line had an advantage over other cell lines in predicting drugs associated with
      DILI in vitro as it had the highest Youden's index (71.4%). A multi-parametric
      screening assay showed that oxidative stress, mitochondrial damage, and disorders
      of neutral lipid metabolism were changed notably in the HepaRG cell line after
      DILI-related drugs exposure, accounting for its high sensitivity in comparison
      with other three cell lines. In addition, aspartate aminotransferase (AST),
      lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) all correlated with
      the cytotoxic effects of diclofenac sodium (p < 0.05), buspirone hydrochloride (p
      < 0.01), and danazol (p < 0.01) in the HepaRG cell line. We conclude that the
      HepaRG cell line is a superior in vitro cell model to other three cell lines for
      evaluating drugs with DILI potential.

PMID- 27027781
TI  - [Bilateral reduction in visual acuity with extensive macular edema].

PMID- 27027782
TI  - A technique for advancing an endotracheal tube over a stylet during intubation
      when an assistant is not available.

PMID- 27027783
TI  - New insights into the evaluation of randomized controlled trials for rare
      diseases over a long-term research horizon: a simulation study.
AB  - Large sample sizes are required in randomized clinical trials designed to meet
      typical one-sided 2.5% alpha-level and 80% power. This may not be achievable when
      the disease is rare. We simulated a series of two-arm superiority trials over a
      15-year period. The design parameters examined were the alpha-level and the
      number of trials conducted over the 15-year period (thus, trial sample size).
      Different disease severities and accrual rates were considered. The future
      treatment effect was characterized by its associated hazard rate; different
      hypotheses of how treatments improve over time were considered. We defined the
      total survival benefit as the relative difference of the hazard rates at year 15
      versus year 0. The optimal design was defined by maximizing the expected total
      survival benefit, provided that the risk of selecting at year 15 a treatment
      inferior to the initial control treatment remains below 1%. Compared with two
      larger trials with typical one-sided 2.5% alpha-level, performing a series of
      small trials with relaxed alpha-levels leads on average to larger survival
      benefits over a 15-year research horizon, but also to higher risk of selecting a
      worse treatment at the end of the research period. Under reasonably optimistic
      assumptions regarding the future treatment effects, optimal designs outperform
      traditional ones when the disease is severe (baseline median survival <= 1 year)
      and the accrual is >=100 patients per year, whereas no major improvement is
      observed in diseases with better prognosis. Trial designs aiming to maximize
      survival gain over a long research horizon across a series of trials are worth
      discussing in the context of rare diseases. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27027785
TI  - Prevention of Cutaneous Penetration and CD1c+ Uptake of Pollen Allergens by a
      Barrier-Enhancing Formulation.
AB  - Recent studies have shown that pollen proteins can penetrate the impaired skin
      barrier of atopic patients and exacerbate their disease. In the presented study
      the effect of a topically applied barrier-enhancing formulation was investigated
      for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal
      cells. The pollen proteins were fluorescence labelled and applied on barrier
      disrupted excised human skin. CD1c+ cells were selected after magnetic cell
      sorting and analysed using laser scanning microscopy. In untreated disrupted
      skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen
      allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an
      uptake of pollen allergens. These results encourage the treatment of atopic
      patients with barrier-enhancing formulations to reduce the impact of pollen on
      air-exposed skin areas and hence the exacerbation of cutaneous symptoms. 

PMID- 27027786
TI  - Defect-Tolerant Monolayer Transition Metal Dichalcogenides.
AB  - Localized electronic states formed inside the band gap of a semiconductor due to
      crystal defects can be detrimental to the material's optoelectronic properties.
      Semiconductors with a lower tendency to form defect induced deep gap states are
      termed defect-tolerant. Here we provide a systematic first-principles
      investigation of defect tolerance in 29 monolayer transition metal
      dichalcogenides (TMDs) of interest for nanoscale optoelectronics. We find that
      the TMDs based on group VI and X metals form deep gap states upon creation of a
      chalcogen (S, Se, Te) vacancy, while the TMDs based on group IV metals form only
      shallow defect levels and are thus predicted to be defect-tolerant.
      Interestingly, all the defect sensitive TMDs have valence and conduction bands
      with a very similar orbital composition. This indicates a bonding/antibonding
      nature of the gap, which in turn suggests that dangling bonds will fall inside
      the gap. These ideas are made quantitative by introducing a descriptor that
      measures the degree of similarity of the conduction and valence band manifolds.
      Finally, the study is generalized to nonpolar nanoribbons of the TMDs where we
      find that only the defect sensitive materials form edge states within the band
      gap. 

PMID- 27027787
TI  - Pre-transplant end-stage renal disease-related immune risk profile in kidney
      transplant recipients predicts post-transplant infections.
AB  - BACKGROUND: End-stage renal disease (ESRD) is associated with premature aging of
      the T-cell system. Nevertheless, the clinical significance of pre-transplant ESRD
      related immune senescence is unknown. METHODS: We studied whether immune risk
      phenotype (IRP), a typical feature of immune senescence, may affect post
      transplant infectious complications. A total of 486 patients were prospectively
      studied during the first year post transplant. IRP was defined as positive
      cytomegalovirus serology with at least 1 of the following criteria: CD4/CD8 ratio
      <1 and/or CD8 T-cell count >90th percentile. RESULTS: We found that 47 patients
      (9.7%) had pre-transplant IRP. IRP+ patients did not differ from IRP- patients
      for any clinical characteristics, but exhibited more pronounced immune
      senescence. Both opportunistic infections (43% vs. 6%, P < 0.001) and severe
      bacterial infection (SBI) (40% vs. 25%, P = 0.028) were more frequent in IRP(+)
      patients. In multivariate analysis, IRP was predictive of both opportunistic
      infection (hazard ratio [HR] 2.97 [95% confidence interval {CI} 1.53-5.76], P =
      0.001), and SBI (HR 2.33 [95% CI 1.34-3.92], P = 0.008). Acute rejection rates
      were numerically much lower in IRP+ patients. A total of 418 patients (86%) had
      biological evaluation 1 year post transplant. Among 41 IRP+ patients, 35 (85%)
      remained IRP+ 1 year post transplant. CONCLUSION: Pre-transplant IRP is
      associated with an increased risk of post-transplant infection.

PMID- 27027788
TI  - De-prescribing: When Less Is More in Healthcare.

PMID- 27027789
TI  - Usefulness of a KT Event to Address Practice and Policy Gaps Related to
      Integrated Care.
AB  - There are limited evaluations of the impact of knowledge translation (KT)
      activities aimed at addressing practice and policy gaps. We report on the impact
      of an interactive, end-of-grant KT event. Although action items were developed
      and key stakeholder support attained, minimal follow-through had occurred three
      months after the KT event. Several organizational obstacles to transitioning
      knowledge into action were identified: leadership, program policies,
      infrastructure, changing priorities, workload and physician engagement. Key
      messages include: (1) ensure ongoing and facilitated networking opportunities,
      (2) invest in building implementation capacity, (3) target multi-level
      implementation activities and (4) focus further research on KT evaluation.

PMID- 27027791
TI  - Cross-Border Healthcare Requests to Publicly Funded Healthcare Insurance:
      Empirical Analysis.
AB  - Despite the legal authority to confirm, override or modify healthcare insurance
      decisions made by physicians and government officials, health tribunal decisions
      have not been empirically analyzed. Using a novel quantitative methodology, all
      387 Health Services Appeal and Review Board written and publicly available
      electronic decisions released over a five-year time period were statistically
      analyzed with respect to Ontario public health insurance requests for global
      cross-border healthcare. The statistical results found that patients knew their
      diagnosis prior to requesting cross-border healthcare, and 84% of patients
      requested specific northern US facilities for specific treatment. Two specific
      healthcare facilities in the US were requested for either surgery or assessments.
      A significant number of patients were seeking cross-border healthcare for pain
      treatment. This research challenges the assumption that cross-border treatment
      requests result only from domestic delay when instead patients are seeking
      specific treatments at specific facilities. This novel quantitative research
      methodology and data source of written and publicly available electronic Health
      Services Appeal and Review Board decisions should be used to inform policy
      decision regarding the utilization and evaluation of Canada's healthcare system
      and publicly funded healthcare insurance.

PMID- 27027790
TI  - Examining Primary Healthcare Performance through a Triple Aim Lens.
AB  - PURPOSE: This study sought to apply a Triple Aim framework to the measurement and
      evaluation of primary healthcare (PHC) team performance. METHODS: Triple Aim
      components were populated with 10 dimensions derived from survey and health
      administrative data for 17 Family Health Teams (FHTs) in Ontario, Canada.
      Bivariate analyses and rankings of sites examined the relationships among
      dimensions and among Triple Aim components. RESULTS: Readily available measures
      to fully populate the Triple Aim framework were lacking in FHTs. Within sites,
      there was little consistency in performance across the Triple Aim components
      (health, patient experience and cost). CONCLUSIONS: More and better measures are
      needed that can be readily used to examine the Triple Aim performance in PHC
      teams. FHTs, in this study, are partially achieving Triple Aim goals; however,
      there was a lack of consistency in performance. It is essential to collect
      appropriate measures and attend to performance across all components of the
      Triple Aim.

PMID- 27027792
TI  - Patient Satisfaction with Wait-Times for Breast Cancer Surgery in Newfoundland
      and Labrador.
AB  - Do shorter waits for breast cancer surgery lead to greater wait-related patient
      satisfaction? Using survey and cancer clinic chart data of 99 patients with
      breast cancer from Newfoundland and Labrador, we found that median wait-time from
      first visit to a surgeon to surgery was 22.0 days and 87% were satisfied with
      their wait-time. Wait-related satisfaction was not associated with the length of
      wait but rather with the stage, severity of treatment, wait-time for a diagnosis
      and satisfaction with diagnosis-related wait. These findings highlight the
      importance of an early and timely diagnosis in patients' perceptions of breast
      cancer care wait-times.

PMID- 27027793
TI  - Impact of Type of Medical Specialist Involvement in Chronic Illness Care on
      Emergency Department Use.
AB  - OBJECTIVES: Medical specialist physicians may act as either consultants or co
      managers for patients managed in primary care settings. We assessed whether the
      type of specialist involvement affected emergency department (ED) use for
      patients with chronic diseases. METHODS: In total, 709 primary care patients with
      arthritis, chronic obstructive pulmonary disease, diabetes or congestive heart
      failure were followed for one year using survey and administrative data.
      Multivariate logistic regressions were used to compare all-cause ED use according
      to specialist involvement (none, co-manager or consultant). RESULTS: In total,
      240 (34%) patients visited the ED. ED use did not differ between those with
      specialist involvement and those without it, either as co-managers (adjusted OR =
      1.06, 95% CI = [0.61, 1.85]) or consultants (adjusted OR = 0.97, 95% CI = [0.63,
      1.50]). DISCUSSION: The type of specialist involvement is not associated with all
      cause ED use in primary care patients with chronic diseases. Indications for co
      management should be further investigated.

PMID- 27027794
TI  - Inappropriate Ambulance Use: A Qualitative Study of Paramedics' Views.
AB  - INTRODUCTION: Existing studies of inappropriate ambulance use focus on its
      extent, employing clinical criteria. Little is known about how front-line
      paramedics assess appropriateness. This study investigates how paramedics view
      and judge appropriate versus inappropriate ambulance use. METHODS: We conducted
      interviews with 19 paramedics working in two regions in southwestern Ontario that
      were analyzed using grounded theory methods. FINDINGS: While blatantly
      "inappropriate" use is extraordinary, "misuse" is more common, and paramedics
      determine misuse largely by interpreting patients' abilities to cope with their
      situations. Paramedics assess this using multiple patient attributes: patient's
      age, knowledge of the system, system failures, social support available, presence
      of transportation alternatives, patient's ability to walk and trial of treatment
      with home remedies. CONCLUSION: In the future, paramedic-informed, contextual and
      non-clinical criteria might supplement clinically based criteria for emergency
      service-use evaluation and may inform more patient-centred policy interventions
      to reduce ambulance misuse and inappropriate use.

PMID- 27027795
TI  - Appropriateness for Total Joint Replacement: Perspectives of Decision-Makers.
AB  - BACKGROUND: Improving access to total joint replacement (TJR) has been a
      priority. Without robust mechanisms to ensure appropriateness, these procedures
      may be overused, incurring substantial costs. In that context, decision-makers
      are particularly concerned with the appropriateness of TJR. OBJECTIVE: While our
      previous research focused on the appropriateness of TJR from clinical and patient
      perspectives, this study is aimed at understanding decision-makers' perspectives.
      METHODS: Using a semi-structured guide, we interviewed a convenience sample of
      decision-makers in four Canadian provinces (Alberta, Manitoba, Nova Scotia and
      Quebec) between February and March 2013. For the purposes of this study, a
      decision-maker was defined as a manager, institutional leader or policy maker.
      RESULTS: Fifteen interviews were conducted with decision-makers at ministry (n =
      3), regional (n = 6) and institutional levels (n = 8). Decision-makers see
      themselves as having a key role in the appropriateness discourse, that of
      optimizing resource allocation and efficient delivery of services for TJR, to
      improve population outcomes. CONCLUSION: The decision-makers' view of
      appropriateness recognizes the importance of the clinical view, but it offers a
      very different input into the appropriateness discourse, more closely aligned
      with appropriateness of setting, which refers to cost-effectiveness
      considerations.

PMID- 27027796
TI  - Exploratory insights from the right-sided electrocardiogram following prolonged
      endurance exercise.
AB  - BACKGROUND: Prolonged strenuous exercise has a profound effect on cardiac
      function. The right heart may be more susceptible to this imposition; yet, right
      sided chest leads have not been utilised in this setting. METHODS: Thirty highly
      trained athletes at the 2014 Western States 100-mile Endurance Run from Squaw
      Valley to Auburn, California (body mass 68 +/- 12 kg, age 45 +/- 10 years, 57 +/-
      15 miles per week) were recruited for the study. Pre- and post-race, a right
      sided 12-lead ECG was obtained and data were extracted for P, R and S waves, J
      point, ST segment and T wave amplitude. Data were compared using Students T-test
      and statistical significance set as P < .05. RESULTS: There was a significant
      increase in P wave amplitude (29%) and QTc interval (4%) pre- to post-race from
      standard 12-lead ECG. From the right-sided12-lead ECG, a 23% (P = .01) and 38% (P
      = .03) increase in J point amplitude in V1R and V2R and a 22% (P = .05) increase
      in ST segment integral in V2R and V3R were evident. T wave inversion was evident
      in leads V2R-V6R in 50-90% of athletes, respectively. Close examination revealed
      marked heterogeneity in individual ECGs. CONCLUSIONS: Completion of a 100-mile
      ultra-marathon resulted in significant changes in the right-sided ECG alongside
      more marked responses in specific individuals. P wave, ST segment and T wave
      changes post-race are indicative of acute exercise-induced right heart electrical
      adaptation.

PMID- 27027797
TI  - Homogenous and Continuous Lesion Formation With Cryoballoon Ablation: Delayed
      Enhancement Magnetic Resonance Imaging Analysis.

PMID- 27027799
TI  - Cancer Chemotherapy.

PMID- 27027800
TI  - Rational Design for Rotaxane Synthesis through Intramolecular Slippage: Control
      of Activation Energy by Rigid Axle Length.
AB  - We describe a new concept for rotaxane synthesis through intramolecular slippage
      using pi-conjugated molecules as rigid axles linked with organic soluble and
      flexible permethylated alpha-cyclodextrins (PM alpha-CDs) as macrocycles. Through
      hydrophilic-hydrophobic interactions and flipping of PM alpha-CDs, successful
      quantitative conversion into rotaxanes was achieved without covalent bond
      formation. The rotaxanes had high activation barrier for their de-threading, so
      that they were kinetically isolated and derivatized even under conditions
      unfavorable for maintaining the rotaxane structures. (1) H NMR spectroscopy
      experiments clearly revealed that the restricted motion of the linked macrocycle
      with the rigid axle made it possible to control the kinetic stability by
      adjusting the length of the rigid axle in the precursor structure rather than the
      steric bulkiness of the stopper unit. 

PMID- 27027798
TI  - Cellular Hypoxia Promotes Heterotopic Ossification by Amplifying BMP Signaling.
AB  - Hypoxia and inflammation are implicated in the episodic induction of heterotopic
      endochondral ossification (HEO); however, the molecular mechanisms are unknown.
      HIF-1alpha integrates the cellular response to both hypoxia and inflammation and
      is a prime candidate for regulating HEO. We investigated the role of hypoxia and
      HIF-1alpha in fibrodysplasia ossificans progressiva (FOP), the most catastrophic
      form of HEO in humans. We found that HIF-1alpha increases the intensity and
      duration of canonical bone morphogenetic protein (BMP) signaling through Rabaptin
      5 (RABEP1)-mediated retention of Activin A receptor, type I (ACVR1), a BMP
      receptor, in the endosomal compartment of hypoxic connective tissue progenitor
      cells from patients with FOP. We further show that early inflammatory FOP lesions
      in humans and in a mouse model are markedly hypoxic, and inhibition of HIF-1alpha
      by genetic or pharmacologic means restores canonical BMP signaling to normoxic
      levels in human FOP cells and profoundly reduces HEO in a constitutively active
      Acvr1(Q207D/+) mouse model of FOP. Thus, an inflammation and cellular oxygen
      sensing mechanism that modulates intracellular retention of a mutant BMP receptor
      determines, in part, its pathologic activity in FOP. Our study provides critical
      insight into a previously unrecognized role of HIF-1alpha in the hypoxic
      amplification of BMP signaling and in the episodic induction of HEO in FOP and
      further identifies HIF-1alpha as a therapeutic target for FOP and perhaps
      nongenetic forms of HEO. (c) 2016 American Society for Bone and Mineral Research.

PMID- 27027801
TI  - Mechanical Construct Characteristics Predisposing to Non-union After Locked
      Lateral Plating of Distal Femur Fractures.
AB  - OBJECTIVES: To identify discrete construct characteristics related to overall
      construct rigidity that may be independent predictors of nonunion after lateral
      locked plate (LLP) fixation of distal femur fractures. DESIGN: Retrospective case
      control study. SETTING: Three level-1 urban trauma centers.
      PATIENTS/PARTICIPANTS: Two hundred and seventy-one supracondylar femoral
      fractures treated with LLP at 3 affiliated level 1 urban trauma centers between
      August 2004 and December 2010. METHODS: Nonunion was defined as a secondary
      procedure for poor healing. Construct variables included: (1) combined plate
      design and material variable, (2) Plate length, (3) # screws proximal to
      fracture, (4) total screw density (TSD), (5) proximal screw density (PSD), (6)
      presence of a screw crossing the main fracture, and (7) rigidity score
      multivariable analysis was performed using logistic regression to identify
      independent risk factors for nonunion. INTERVENTION: LLP fixation. MAIN OUTCOME
      MEASURE: Nonunion. RESULTS: Nonunion rate was 13.3% (n = 36). There was a
      significant association between plate design/material and nonunion with 41% of
      stainless constructs and 10% of titanium constructs resulting in a nonunion (P <
      0.001). Rigidity scores reached significance (P = 0.001) with constructs
      resulting in a nonunion having higher scores. No significant univariate
      differences with respect to number of proximal screws, plate length, total screw
      density, or proximal screw density were observed between healed fractures and
      those with nonunion. Results of the multivariate analysis confirmed that the
      primary significant independent predictor of nonunion was plate design/material
      (odds ratio, 6.8; 95% CI, 2.9-16.1; P < 0.001). CONCLUSIONS: When treating distal
      femur fractures with LLP, combined plate design and material variable has a
      highly significant influence on the risk of nonunion independent of any other
      construct variable. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 27027802
TI  - Relationship of body mass index with efficacy of exenatide twice daily added to
      insulin glargine in patients with type 2 diabetes.
AB  - This post hoc analysis assessed the evidence behind common reimbursement
      practices by evaluating the relationship of body mass index (BMI) ranges (<30, 30
      35 and >35 kg/m(2) ) with treatment effects of exenatide twice daily among
      patients with type 2 diabetes. Patients received exenatide twice daily added to
      insulin glargine in two 30-week studies (exenatide twice daily vs insulin lispro,
      n = 627; exenatide twice daily vs placebo, n = 259). No association of baseline
      BMI with changes in efficacy variables was observed. Glycated haemoglobin (HbA1c)
      reductions were significant (p < 0.0001) and similar across BMI range groups in
      the lispro-comparator study and greater for exenatide versus placebo in the
      placebo-controlled study. Significant weight loss occurred with exenatide across
      BMI range groups (p < 0.0001), while weight increased with both comparators.
      Achievement of HbA1c <7.0% (<53 mmol/mol) without weight gain was greater for
      exenatide versus comparators. Systolic blood pressure decreased across BMI range
      groups with exenatide in the lispro-comparator study (p < 0.0001); changes in
      lipids were not clinically meaningful. Minor hypoglycaemia was less frequent for
      exenatide versus insulin lispro. These findings suggest that BMI alone should not
      limit clinical decision-making or patient access to medication.

PMID- 27027804
TI  - Re: "Telepharmacotherapy for Child and Adolescent Psychiatric Patients" by Cain
      and Sharp (J Child Adolesc Psychopharm 2016;26:221-228).

PMID- 27027803
TI  - MYC translocation and/or BCL 2 protein expression are associated with poor
      prognosis in diffuse large B-cell lymphoma.
AB  - Genomic alterations and protein expression levels have been established as
      prognostic factors for survival in patients with diffuse large B-cell lymphoma
      (DLBCL). In particular, double-hit DLBCL (DHL), which exhibits translocations in
      MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis.
      However, the clinical significance of gene alterations and protein expression
      levels for MYC, B-cell lymphoma (BCL)2, and BCL6 are unclear. In this study, we
      analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated
      with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, or
      similar regimens. There were no differences in the distribution of MYC expression
      rates among the different MYC gene statuses. In log-rank tests, MYC translocation
      was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and
      BCL6 translocation were not prognostic indicators (P = 0.999 and P = 0.925,
      respectively). Although the expression levels of MYC and BCL6 were not
      significantly associated with OS, the expression of BCL2 was a prognostic factor
      for OS (P = 0.027). Furthermore, copy number gains in the MYC, BCL2, and BCL6
      genes did not affect OS. MYC translocation (hazard ratio, 4.769; range, 1.518
      14.98; P = 0.007) and BCL2 protein expression (hazard ratio, 3.072; range, 1.002
      9.413; P = 0.049) were independent prognostic factors for survival in
      multivariate analyses. In conclusion, MYC translocation and BCL2 expression may
      need to be investigated at the initial diagnosis to predict prognosis in patients
      with DLBCL. 

PMID- 27027806
TI  - Light microscopy of whole plant organs.
AB  - Plants are ideal organisms for light microscopical studies of cellular mechanisms
      controlling cell organisation and cell functioning. However, most plant organs
      are not transparent to light which prevents high resolution imaging deep within
      plant tissues. Classically, access into plant organs is achieved by sectioning or
      whole-mount tissue clearing. Until recently, the protocols for clearing destroyed
      the signal from fluorescent markers which prevented the imaging of the
      distribution of fluorescent proteins and the three-dimensional reconstruction
      from optical slices of whole plant organs. From 2011, a number of protocols have
      been developed for whole brain and whole organism imaging for animal studies.
      Now, these protocols have been adapted for in-depth imaging of whole plant
      organs. Here, I present an overview of clearing techniques of plant organs and
      highlight the latest developments of plant tissue clearing in combination with
      high resolution fluorescence microscopy.

PMID- 27027805
TI  - Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer
      Retina: Disease Modeling and Cell Replacement.
AB  - Stem cell therapies are being explored as potential treatments for retinal
      disease. How to replace neurons in a degenerated retina presents a continued
      challenge for the regenerative medicine field that, if achieved, could restore
      sight. The major issues are: (i) the source and availability of donor cells for
      transplantation; (ii) the differentiation of stem cells into the required retinal
      cells; and (iii) the delivery, integration, functionality, and survival of new
      cells in the host neural network. This review considers the use of induced
      pluripotent stem cells (iPSC), currently under intense investigation, as a
      platform for cell transplantation therapy. Moreover, patient-specific iPSC are
      being developed for autologous cell transplantation and as a tool for modeling
      specific retinal diseases, testing gene therapies, and drug screening.

PMID- 27027807
TI  - Protein corona formation in bronchoalveolar fluid enhances diesel exhaust
      nanoparticle uptake and pro-inflammatory responses in macrophages.
AB  - In biological fluids nanoparticles bind a range of molecules, particularly
      proteins, on their surface. The resulting protein corona influences biological
      activity and fate of nanoparticle in vivo. Corona composition is often determined
      by the biological milieu encountered at the entry portal into the body, and, can
      therefore, depend on the route of exposure to the nanoparticle. For environmental
      nanoparticles where exposure is by inhalation, this will be lung lining fluid.
      This study examined plasma and bronchoalveolar fluid (BALF) protein binding to
      engineered and environmental nanoparticles. We hypothesized that protein corona
      on nanoparticles would influence nanoparticle uptake and subsequent pro
      inflammatory biological response in macrophages. All nanoparticles bound plasma
      and BALF proteins, but the profile of bound proteins varied between
      nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified
      proteins bound from plasma to include fibrinogen, and those bound from BALF to
      include albumin and surfactant proteins A and D. The presence on DENP of a plasma
      derived corona or one of purified fibrinogen failed to evoke an inflammatory
      response in macrophages. However, coronae formed in BALF increased DENP uptake
      into macrophages two fold, and increased nanoparticulate carbon black (NanoCB)
      uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from
      macrophages in response to DENP from 1720 +/- 850 pg/mL to 5560 +/- 1380 pg/mL (p
      = 0.014). These results demonstrate that the unique protein corona formed on
      nanoparticles plays an important role in determining biological reactivity and
      fate of nanoparticle in vivo. Importantly, these findings have implications for
      the mechanism of detrimental properties of environmental nanoparticles since the
      principle route of exposure to such particles is via the lung.

PMID- 27027808
TI  - Renal disease screening: a potential tool for reducing health inequity.

PMID- 27027809
TI  - Screening for physical inactivity among adults: the value of distance walked in
      the six-minute walk test. A cross-sectional diagnostic study.
AB  - CONTEXT AND OBJECTIVES: Accelerometry provides objective measurement of physical
      activity levels, but is unfeasible in clinical practice. Thus, we aimed to
      identify physical fitness tests capable of predicting physical inactivity among
      adults. DESIGN AND SETTING: Diagnostic test study developed at a university
      laboratory and a diagnostic clinic. METHODS: 188 asymptomatic subjects underwent
      assessment of physical activity levels through accelerometry, ergospirometry on
      treadmill, body composition from bioelectrical impedance, isokinetic muscle
      function, postural balance on a force platform and six-minute walk test. We
      conducted descriptive analysis and multiple logistic regression including age,
      sex, oxygen uptake, body fat, center of pressure, quadriceps peak torque,
      distance covered in six-minute walk test and steps/day in the model, as
      predictors of physical inactivity. We also determined sensitivity (S),
      specificity (Sp) and area under the curve of the main predictors by means of
      receiver operating characteristic curves. RESULTS: The prevalence of physical
      inactivity was 14%. The mean number of steps/day (<= 5357) was the best predictor
      of physical inactivity (S = 99%; Sp = 82%). The best physical fitness test was a
      distance in the six-minute walk test and <= 96% of predicted values (S = 70%; Sp
      = 80%). Body fat > 25% was also significant (S = 83%; Sp = 51%). After logistic
      regression, steps/day and distance in the six-minute walk test remained
      predictors of physical inactivity. CONCLUSION: The six-minute walk test should be
      included in epidemiological studies as a simple and cheap tool for screening for
      physical inactivity.

PMID- 27027810
TI  - Preventing occupational stress in healthcare workers.
AB  - BACKGROUND: Healthcare workers can suffer from occupational stress which may lead
      to serious mental and physical health problems. OBJECTIVES: To evaluate the
      effectiveness of work and person-directed interventions in preventing stress at
      work in healthcare workers. METHODS:  SEARCH METHODS: We searched the Cochrane
      Depression Anxiety and Neurosis Group trials Specialised Register, MEDLINE,
      PsychInfo and Cochrane Occupational Health Field database. SELECTION CRITERIA:
      Randomised controlled clinical trials (RCT) of interventions aimed at preventing
      psychological stress in healthcare workers. For work-directed interventions
      interrupted time series and prospective cohort were also eligible. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      trial quality. Meta-analysis and qualitative synthesis were performed where
      appropriate. MAIN RESULTS: We identified 14 RCTs, three cluster-randomised trials
      and two crossover trials, including a total of 1,564 participants in intervention
      groups and 1,248 controls. Two trials were of high quality. Interventions were
      grouped into 1) person-directed: cognitive-behavioural, relaxation, music-making,
      therapeutic massage and multicomponent; and 2) work-directed: attitude change and
      communication, support from colleagues and participatory problem solving and
      decision-making, and changes in work organisation. There is limited evidence that
      person-directed interventions can reduce stress (standardised mean difference or
      SMD -0.85; 95% CI -1.21, -0.49); burnout: Emotional Exhaustion (weighted mean
      difference or WMD -5.82; 95% CI -11.02, -0.63) and lack of Personal
      Accomplishment (WMD -3.61; 95% CI -4.65, -2.58); and anxiety: state anxiety (WMD 
      9.42; 95% CI -16.92, -1.93) and trait anxiety (WMD -6.91; 95% CI -12.80, -1.01).
      One trial showed that stress remained low a month after intervention (WMD -6.10;
      95% CI -8.44, -3.76). Another trial showed a reduction in Emotional Exhaustion
      (Mean Difference or MD -2.69; 95% CI -4.20, -1.17) and in lack of Personal
      Accomplishment (MD -2.41; 95% CI -3.83, -0.99) maintained up to two years when
      the intervention was boosted with refresher sessions. Two studies showed a
      reduction that was maintained up to a month in state anxiety (WMD -8.31; 95% CI 
      11.49, -5.13) and trait anxiety (WMD -4.09; 95% CI -7.60, -0.58). There is
      limited evidence that work-directed interventions can reduce stress symptoms
      (Mean Difference or MD -0.34; 95% CI -0.62, -0.06); Depersonalization (MD -1.14;
      95% CI -2.18, -0.10), and general symptoms (MD -2.90; 95% CI -5.16, -0.64). One
      study showed that the difference in stress symptom level was nonsignificant at
      six months (MD -0.19; 95% CI -0.49, 0.11). AUTHORS' CONCLUSIONS: Limited evidence
      is available for the effectiveness of interventions to reduce stress levels in
      healthcare workers. Larger and better quality trials are needed.

PMID- 27027811
TI  - Management of connective tissue diseases associated interstitial lung disease: a
      review of the published literature.
AB  - PURPOSE OF REVIEW: Interstitial lung disease (ILD), though a common and often a
      severe manifestation of many connective tissue diseases (CTD), is challenging to
      manage because of its variable presentation and the relative lack of guidelines
      to assist the clinician. In this review, we discuss the approach to diagnosis,
      treatment, and monitoring patients with CTD-associated ILD, with a focus on
      systemic sclerosis (SSc), rheumatoid arthritis (RA), and idiopathic inflammatory
      myopathy (IIM). RECENT FINDINGS: High-resolution computed tomography scan and
      pulmonary function testing can be reliably used to diagnose ILD and monitor
      progression, and often to determine its likely histologic subtype and severity.
      In SSc-ILD, randomized controlled trials show ILD stabilization with
      cyclophosphamide treatment; preliminary data from another randomized controlled
      trial demonstrates similar findings with mycophenolate. There are no robust
      clinical trials supporting specific treatments for RA-ILD or IIM-ILD, but
      rituximab in RA-ILD, and cyclophosphamide, mycophenolate and calcineurin
      inhibitors in IIM-ILD show promise. SUMMARY: Though ILD contributes substantially
      to morbidity and mortality in patients with CTD, there are minimal data to guide
      its management except in SSc-ILD.

PMID- 27027812
TI  - Suppression of normal immune responses after treatment with rituximab.
AB  - PURPOSE OF REVIEW: Because rituximab is increasingly used in systemic autoimmune
      diseases, alone or in combination with other immunosuppressive medication,
      secondary reduction of normal immune defenses has become a more significant
      clinical problem. RECENT FINDINGS: The goal of rituximab treatment of immune
      mediated conditions is complete depletion of circulating B cells. Studies have
      suggested that lack of complete B-cell depletion is associated with nonresponse,
      and B-cell repletion can predict relapse. The resulting prolonged B-cell
      depletion is associated with risk of adverse effects including
      hypogammaglobulinemia, increased risk of infection, failure to develop immune
      responses after vaccination, and neutropenia. Pre-existing hypogammaglobulinemia
      has been linked to increased risk of reduction of IgG levels and serious
      infections after rituximab therapy, and concomitant cyclophosphamide therapy has
      been associated with an increased risk of developing hypogammaglobulinemia.
      SUMMARY: Although rituximab therapy is effective in the treatment of many
      systemic autoimmune diseases and has an acceptable safety profile, treating
      physicians need to keep in mind that pre-existing hypogammaglobulinemia and
      likely also use of additional immunosuppressive agents can increase the risk of
      prolonged hypogammaglobulinemia and infection. In keeping with current
      recommendations for rheumatoid arthritis, we recommend that all patients who
      undergo rituximab therapy have baseline IgG, IgM, and IgA measurements and also
      have immunoglobulin levels monitored periodically during treatment.

PMID- 27027813
TI  - A new window of opportunity in rheumatoid arthritis: targeting at-risk
      individuals.
AB  - PURPOSE OF REVIEW: Progress in our understanding of the preclinical events in
      rheumatoid arthritis (RA) has provided important insights into disease
      pathogenesis. Studying prospective cohorts of individuals at risk for RA
      development offers the opportunity to accurately characterize the sequence of
      events in preclinical disease as well as quantify the risk of different
      preclinical phenotypes. These data may provide the basis for preventive
      strategies in RA. RECENT FINDINGS: RA-related systemic autoimmunity and
      inflammation occur long before clinical arthritis. There is growing evidence that
      initiating events may occur at mucosal surfaces including the periodontium, lung
      and gut and may be influenced by the local microbiome. For potential preventive
      strategies to be feasible, it is important that individuals at high risk for RA
      development can be readily identified from the general population. To this end,
      studying multiple biomarkers in prospective cohorts of at-risk individuals
      enables risk prediction in different at-risk phenotypes. RA prevention using
      immunomodulation is currently being investigated in individuals at high risk of
      RA development. SUMMARY: The prospective study of at-risk individuals can provide
      invaluable aetiological insights as well as facilitating accurate risk prediction
      data. In this way, high-risk individuals may be identified for preventive
      interventions.

PMID- 27027814
TI  - Comorbidities in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: The aim of this study was to give an overview of recently
      published articles covering comorbidities in rheumatoid arthritis with a specific
      focus on their implications in daily practice and clinical research studies.
      RECENT FINDINGS: Recent studies have confirmed the higher incidence/prevalence of
      some comorbidities in rheumatoid arthritis such as atherosclerosis-related
      cardiovascular diseases, some cancers, infections and osteoporosis. Apart from
      the interest in the underlying pathophysiological pathway, such studies have
      pointed out the impact of comorbidities on the course of the disease and also on
      the efficacy and tolerability of frequently used antirheumatic drugs. Such
      findings have prompted the rheumatology community to propose a standardized way
      to collect and to prevent these comorbidities. SUMMARY: Several comorbidities are
      frequently observed in rheumatoid arthritis because of the persistent activity of
      the disease and/or because of the administered antirheumatic therapies. Programs
      to adequately collect these comorbidities and/or prevent them are resulting in a
      better outcome for rheumatoid arthritis patients.

PMID- 27027815
TI  - Treat-to-target as an approach in inflammatory arthritis.
AB  - PURPOSE OF REVIEW: Treat-to-target (T2T) is a new paradigm in the treatment of
      rheumatoid arthritis (RA). This review is timely, because the evidence is
      compelling and the world's major organizations have included it in their
      management recommendations. RECENT FINDINGS: T2T involves regular disease
      activity monitoring, ideally using the most recently described composite measures
      and remission criteria. The findings in the literature fully support previous
      notions on prevention of damage, maintenance of physical function and reduction
      of comorbidity risks using this strategy in early RA and have expanded these
      insights to established RA, elderly patients and work capacity. T2T has now even
      been advocated for psoriatic arthritis and is suggested of value also for
      ankylosing spondylitis and systemic lupus erythematosus. SUMMARY: This paradigm
      is independent of the availability of particular drugs, as the strategy in itself
      will maximize the benefit for the patient, irrespective of specific medications.
      Adhering to this strategy in clinical practice will optimize the outcomes in
      patients with RA.

PMID- 27027816
TI  - Fine-Needle Aspiration Cytology of Intranodal Palisaded Myofibroblastoma of the
      Inguinal Lymph Node.
AB  - BACKGROUND: Intranodal palisaded myofibroblastoma (IPM) is a rare, lymph node
      mesenchymal neoplasm; the cytologic features are limited in the literature. CASE:
      The patient was a 51-year-old female who had a firm, palpable mass in the right
      inguinal region. Fine-needle aspiration (FNA) was performed. The smears revealed
      large, 3-dimensional clusters of cohesive spindle cells, densely surrounding a
      central, orange-colored, acellular matrix core. These cells had a single,
      elongated nucleus and an inconspicuous nucleolus. Also seen were spindle cells in
      short fascicles with dense cytoplasm. The spindle cells were loosely arranged in
      a single-cell pattern. In addition to the spindle cells and matrix, hemosiderin
      granules were scattered in the background. A few lymphocytes were identified.
      CONCLUSION: A diagnosis of IPM should be considered when FNA smears of lymph node
      show bland spindle cells in various patterns including single cells, short
      fascicles, large cohesive clusters with core amianthoid fibers and background
      hemosiderin granules.

PMID- 27027817
TI  - Novel S1P1 receptor agonists - Part 5: From amino-to alkoxy-pyridines.
AB  - In a previous communication we reported on the discovery of aminopyridine 1 as a
      potent, selective and orally active S1P1 receptor agonist. More detailed studies
      revealed that this compound is phototoxic in vitro. As a result of efforts aiming
      at eliminating this undesired property, a series of alkoxy substituted pyridine
      derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy
      pyridines was significantly lower than the one of aminopyridine 1 and most
      compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4
      pyridine derivatives delivered highly potent S1P1 receptor agonists. While the 2
      pyridines were clearly more selective against S1PR3, the corresponding 3- or 4
      pyridine analogues showed significantly longer oral half-lives and as a
      consequence longer pharmacological duration of action after oral administration.
      One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed
      EC50 values of 0.7 and 140 nM on S1PR1 and S1PR3, respectively, and maximally
      reduced the blood lymphocyte count for at least 24 h after oral administration of
      10 mg/kg to Wistar rats. 

PMID- 27027818
TI  - Design and synthesis of diamide-coupled benzophenones as potential anticancer
      agents.
AB  - A series of diamide-coupled benzophenone, 2-(4-benzoyl-phenoxy)-N-{2-[2-(4
      benzoyl-phenoxy)-acetylamino]-phenyl}-acetamide analogues (9a-l) were synthesized
      by multistep reactions and all compounds were well characterized. Among the
      series (9a-l), compound 9k with three methyl groups at ortho position in rings A,
      B, and D and bromo group at the para position in ring E was selected as a lead
      compound by screening through multiple cancer cell types by in-vitro cytotoxic
      and antiproliferative assay systems. Also, the cytotoxic nature of the compound
      9k resulted the regression of the tumor growth in-vivo, which could be due to
      decreased vascularisation in the peritoneum lining of the mice which regress the
      tumor growth. The results were reconfirmed in-vivo chorioallantoic membrane model
      which indicates a scope of developing 9k into potent anticancer drug in near
      future. 

PMID- 27027819
TI  - HLA-B*40:327, a novel HLA-B*40 variant, discovered in a Taiwanese blood donor.
AB  - One nucleotide substitution at residue 220 of HLA-B*40:01:01 results in a new
      allele, HLA-B*40:327. 

PMID- 27027820
TI  - Effect of Temperature on the Desorption of Lithium from Molybdenum(110) Surfaces:
      Implications for Fusion Reactor First Wall Materials.
AB  - Determining the strength of Li binding to Mo is critical to assessing the
      survivability of Li as a potential first wall material in fusion reactors. We
      present the results of a joint experimental and theoretical investigation into
      how Li desorbs from Mo(110) surfaces, based on what can be deduced from
      temperature-programmed desorption measurements and density functional theory
      (DFT). Li desorption peaks measured at temperatures ranging from 711 K (1
      monolayer, ML) to 1030 K (0.04 ML), with corresponding desorption onsets from 489
      to 878 K, follow a trend similar to predicted Gibbs free energies for Li
      adsorption. Bader charge analysis of DFT densities reveals that repulsive forces
      between neighboring positively charged Li atoms increase with coverage and thus
      reduce the bond strength between Mo and Li, thereby lowering the desorption
      temperature as the coverage increases. Additionally, DFT predicts that Li desorbs
      at higher temperatures from a surface with vacancies than from a perfect surface,
      offering an explanation for the anomalously high desorption temperatures for the
      last Li to desorb from Mo(110). Analysis of simulated local densities of states
      indicates that the stronger binding to the defective surface is correlated with
      enhanced interaction between Li and Mo, involving the Li 2s electrons and not
      only the Mo 4d electrons as in the case of the pristine surface, but also the Mo
      5s electrons in the case with surface vacancies. We suggest that steps and kinks
      present on the Mo(110) surface behave similarly and contribute to the high
      desorption temperatures. These findings imply that roughened Mo surfaces may
      strengthen Li film adhesion at higher temperatures.

PMID- 27027821
TI  - Biosynthesis of silver nanoparticles using Aeromonas sp. THG-FG1.2 and its
      antibacterial activity against pathogenic microbes.
AB  - Silver nanoparticles were prepared through green route with the aid of Aeromonas
      sp. THG-FG1.2 as reductant. Visual observation, ultraviolet-visible spectroscopy,
      transmission electron microscopy, elemental mapping, energy dispersive X-ray
      spectroscopy, selected area diffraction pattern (SAED), and X-ray diffraction
      (XRD) were used to characterize the synthesized silver nanoparticles. UV visible
      studies indicated the surface plasmon resonance at 400 nm which depicts the
      formation of silver nanoparticles. The TEM images show spherical silver
      nanoparticles of 8-16 nm. XRD and SAED fringes revealed the structure of silver
      nanoparticles as face centered cubic (fcc). These silver nanoparticles also
      tested for their antimicrobial potential and showed effective antimicrobial
      activity against tested pathogens and thus applicable as potent antimicrobial
      agent. Furthermore, the nanoparticles potential has been reconnoitered for their
      enhanced synergistic effect with antibiotics against multidrug resistant
      bacteria. Thus, the silver nanoparticles synthesized by Aeromonas sp. THG-FG1.2,
      were effective in inhibition of pathogenic microbes and also show enhanced
      antibacterial activity with antibiotics.

PMID- 27027822
TI  - Nature-Inspired, Highly Durable CO2 Reduction System Consisting of a Binuclear
      Ruthenium(II) Complex and an Organic Semiconductor Using Visible Light.
AB  - A metal-free organic semiconductor of mesoporous graphitic carbon nitride (C3N4)
      coupled with a Ru(II) binuclear complex (RuRu') containing photosensitizer and
      catalytic units selectively reduced CO2 into HCOOH under visible light (lambda >
      400 nm) in the presence of a suitable electron donor with high durability, even
      in aqueous solution. Modification of C3N4 with Ag nanoparticles resulted in a
      RuRu'/Ag/C3N4 photocatalyst that exhibited a very high turnover number (>33000
      with respect to the amount of RuRu'), while maintaining high selectivity for
      HCOOH production (87-99%). This turnover number was 30 times greater than that
      reported previously using C3N4 modified with a mononuclear Ru(II) complex, and by
      far the highest among the metal-complex/semiconductor hybrid systems reported to
      date. The results of photocatalytic reactions, emission decay measurements, and
      time-resolved infrared spectroscopy indicated that Ag nanoparticles on C3N4
      collected electrons having lifetimes of several milliseconds from the conduction
      band of C3N4, which were transferred to the excited state of RuRu', thereby
      promoting photocatalytic CO2 reduction driven by two-step photoexcitation of C3N4
      and RuRu'. This study also revealed that the RuRu'/Ag/C3N4 hybrid photocatalyst
      worked efficiently in water containing a proper electron donor, despite the
      intrinsic hydrophobic nature of C3N4 and low solubility of CO2 in an aqueous
      environment. 

PMID- 27027823
TI  - Downregulated serum miR-223 servers as biomarker in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is
      characterized by progressive memory loss and deteriorated higher cognitive
      functions. An economical, rapid and noninvasive biomarker for AD has not been
      identified. We aimed to investigate the diagnostic value of serum miR-223 and miR
      519 in AD. The expressions of miR-223 and miR-519, with previously reported AD
      associated miR-29 and miR-125b, were measured by quantitative reverse
      transcription polymerase chain reaction in the serum of 84 probable sporadic AD
      patients (age onset > 65 years) and 62 healthy control populations in China.
      Analyses were undertaken to assess the specificity and sensitivity of miRNAs to
      predict AD. In addition, the relationship between miRNAs and mini mental state
      examination (MMSE) scores in AD patients was also assessed. Serum miR-29, miR
      125b and miR-223 were significantly decreased, but serum miR-519 was
      significantly increased in AD patients compared with healthy blood donors. In
      addition, serum miR-223 was strongly positively correlated with MMSE score in AD
      patients but serum miR-519 was not. Importantly, the receiver operating
      characteristic (ROC) result of serum miR-223 for prediction of AD was 0.786,
      higher than those of serum miR-29 (0.734) or miR-125b (0.726). The combination of
      serum miR-223 and miR-125b gave improved sensitivity/specificity for AD
      prediction (area under the ROC curve, 0.879) than either miRNA alone. Our
      preliminary findings indicate that serum miR-223 might be a potential biomarker
      for AD evaluation. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27027824
TI  - Hematopoietic Effect of Amaranthus cruentus Extract on Phenylhydrazine-Induced
      Toxicity in Rats.
AB  - Amaranthus cruentus (Amaranthaceae) is one of the popularly grown leafy
      vegetables in the Indian subcontinent. Leaves of the plant are rich in
      polyphenols, tannins, flavonoids, steroids, terpenoids, saponins, and betalains.
      The plant also contains rich amounts of protein, calcium, iron, vitamins A, E,
      and C, and folic acid. The present work was undertaken to evaluate the antianemic
      effect of Amaranthus cruentus. Ethanol extract of Amaranthus cruentus was
      prepared. Acute oral toxicity of the extract was determined by Organization for
      Economic Cooperation and Development (OECD) Guideline 423. Doses of 200 and 400
      mg/kg were used in the present study. Phenylhydrazine (60 mg/kg, intraperitoneal
      injection for three consecutive days) was used to induce anemia in rats. After
      anemia induction, animals were treated with standard preparation and extract.
      Amaranthus cruentus extract significantly aided in restoring the levels of red
      blood cells, white blood cells (WBCs), and hemoglobin. There was also an increase
      in hematocrit. Thus, it can be concluded that Amaranthus cruentus is a rich
      source of phytochemicals that are responsible for demonstrating hematopoietic
      effects. Isolation and structure elucidation of constituents, responsible for
      antianemic activity, is necessary to affirm the aforementioned effect. 

PMID- 27027825
TI  - Imaging photoplethysmography for clinical assessment of cutaneous
      microcirculation at two different depths.
AB  - The feasibility of bispectral imaging photoplethysmography (iPPG) system for
      clinical assessment of cutaneous microcirculation at two different depths is
      proposed. The iPPG system has been developed and evaluated for in vivo conditions
      during various tests: (1) topical application of vasodilatory liniment on the
      skin, (2) skin local heating, (3) arterial occlusion, and (4) regional
      anesthesia. The device has been validated by the measurements of a laser Doppler
      imager (LDI) as a reference. The hardware comprises four bispectral light sources
      (530 and 810 nm) for uniform illumination of skin, video camera, and the control
      unit for triggering of the system. The PPG signals were calculated and the
      changes of perfusion index (PI) were obtained during the tests. The results
      showed convincing correlations for PI obtained by iPPG530 nm and LDI at (1)
      topical liniment (r = 0.98) and (2) heating (r = 0.98) tests. The topical
      liniment and local heating tests revealed good selectivity of the system for
      superficial microcirculation monitoring. It is confirmed that the iPPG system
      could be used for assessment of cutaneous perfusion at two different depths,
      morphologically and functionally different vascular networks, and thus utilized
      in clinics as a cost-effective alternative to the LDI.

PMID- 27027826
TI  - Early diagnosis of Balo's concentric sclerosis by diffusion tensor tractography:
      a case report and literature review.
AB  - Balo concentric sclerosis is an infrequent variant of a demyelinating disease
      related to multiple sclerosis, initially thought to have an acute presentation
      and a fatal outcome. Recent studies have reported non-fatal forms of Balo
      concentric sclerosis, focusing on the importance of early diagnosis using
      magnetic resonance imaging (MRI), along with spectroscopy and diffusion/perfusion
      sequences. Recently, we have been able to draw a three-dimensional image of a
      specific bundle of fibers by means of a diffusion tensor technique of the
      magnetic resonance imaging tractography (t-MRI). We report the case of a young
      woman presenting with acute and progressive focal neurological symptoms,
      including right body paresis, whose diagnosis was suggested by MRI and confirmed
      by pathology to be Balo concentric sclerosis. She was treated with boluses of
      methylprednisolone, achieving full neurological remission one year after
      admission. This is, to our knowledge, the first report describing the use of t
      MRI for diagnosing BCS. We consider that t-MRI will allow, in a near future,
      early diagnosis of the disease, its prompt treatment, and establishing new
      classification criteria. This case confirms the existence of benign forms of Balo
      concentric sclerosis with a good response to steroid therapy, where functional
      recovery is possible. 

PMID- 27027827
TI  - Helicobacter pylori: past, current and future treatment strategies with
      gastroretentive drug delivery systems.
AB  - Helicobacter pylori have been subject to intense investigation since its
      discovery from gastric biopsy in 1982. This gastropathogen has been regarded as
      serious public health problem due to its association with dyspepsia, gastritis,
      gastroduodenal ulcers, mucus-associated lymphoid tissue lymphoma and gastric
      carcinoma. In vivo eradication of established H. pylori infections is difficult
      due to several factors such as gastric niche, coccoid form due to sub-minimum
      inhibitory concentration of antimicrobials, bacterial load, primary antibiotic
      resistance, patient compliance and stability of therapeutics in gastric acid
      secretion. Considering these factors, a logical way to improve the outcome of the
      treatment is to develop dosage forms which are able to deliver the anti
      helicobacter agents in the gastric niche for both local and systemic actions,
      simultaneously taking care of stability of therapeutics in acidic environment.
      Such dosage forms, which are popularly known as gastro retentive drug delivery
      systems (GRDDS), have the immense potential to effectively counter the problem of
      high bacterial load; prevent induction of coccoid bacteria thereby improving
      treatment outcome and compliance. This review describes efficacy of various
      therapeutic agents, treatment strategies and status of different GRDDS until now.

PMID- 27027828
TI  - Current Status and Challenges of Laparoscopy in Ventral Hernia Repair.
AB  - Laparoscopic repair of ventral hernias gained strong popularity in the late
      nineties with some of the early enthusiasm lost later in time. We review the
      current status and challenges of laparoscopy in ventral hernia repair and best
      practices in this area. We specifically looked at patient and hernia defect
      factors, technical considerations that have contributed to the successes, and
      some of the failures of laparoscopic ventral hernia repair (LVHR). Patients best
      suited for a laparoscopic repair are those who are obese and diabetic with a
      total defect size not to exceed 10 cm in width or a "Swiss cheese" defect.
      Overlap of mesh to healthy fascia of at least 5 cm in every direction, with
      closure of the defect, is essential to prevent recurrence or bulging over time.
      Complications specifically related to surgical site occurrence favor the
      laparoscopic approach. Recurrence rates, satisfaction, and health-related quality
      of life results are similar to open repairs, but long-term data are lacking.
      There is still conflicting data regarding ways of fixating the mesh. The science
      of prosthetic material appropriate for intraperitoneal placement continues to
      evolve. The field continues to be plagued by single author, single institution,
      and small nonrandomized observational studies with short-term follow-up. The
      recent development of large prospective databases might allow for pragmatic and
      point-of-care studies with long-term follow-up. We conclude that LVHR has evolved
      since its inception, has overcome many challenges, but still needs better long
      term studies to evaluate evolving practices. 

PMID- 27027831
TI  - Associations of force plate and body-mounted inertial sensor measurements for
      identification of hind limb lameness in horses.
AB  - OBJECTIVE: To investigate associations between inertial sensor and stationary
      force plate measurements of hind limb lameness in horses. ANIMALS: 21 adult
      horses with no lameness or with mild hind limb lameness. PROCEDURES: Horses were
      instrumented with inertial sensors and evaluated for lameness with a stationary
      force plate while trotting in a straight line. Inertial sensor-derived
      measurements of maximum and minimum pelvic height differences between right and
      left halves of the stride were compared with vertical and horizontal ground
      reaction forces (GRFs). Stepwise linear regression was performed to investigate
      the strength of association between inertial sensor measurements of hind limb
      lameness and amplitude, impulse, and time indices of important events in the
      vertical and horizontal GRF patterns. RESULTS: Difference in minimum pelvic
      position was moderately (Ra(2) = 0.60) associated with the difference in peak
      vertical GRF but had little association with any horizontal GRF measurements.
      Difference in maximum pelvic position was strongly (Ra(2) = 0.77) associated with
      a transfer of vertical to horizontal ground reaction impulse in the second half
      of the stance but was not associated with difference in peak vertical GRF.
      CONCLUSIONS AND CLINICAL RELEVANCE: Inertial sensor-derived measurements of
      asymmetric pelvic fall (difference in minimum pelvic position) indicated a
      decrease in vertical GRF, but similar measurements of asymmetric pelvis rise
      (difference in maximum pelvic position) indicated a transfer of vertical to
      horizontal force impulse in the second half of the stance. Evaluation of both
      pelvic rise and fall may be important when assessing hind limb lameness in
      horses.

PMID- 27027832
TI  - Temporal effects of intramuscular administration of medetomidine hydrochloride or
      xylazine hydrochloride to healthy dogs on tear flow measured by use of a Schirmer
      tear test I.
AB  - OBJECTIVE: To determine the temporal effects on tear flow measurements obtained
      by use of a Schirmer tear test (STT) I after IM administration of various doses
      of medetomidine or xylazine to healthy dogs. ANIMALS: 5 healthy purpose-bred male
      Beagles. PROCEDURES: Each dog received IM injections of 2.0 mL of physiologic
      saline (0.9% NaCl) solution (control treatment); 0.1% medetomidine hydrochloride
      (5, 10, 20, and 40 MUg/kg), and 2.0% xylazine hydrochloride (0.5, 1.0, 2.0, and
      4.0 mg/kg). Treatments were injected into the semimembranosus muscles; there was
      at least a 1-week interval between successive injections. Order of treatments was
      determined via a randomized Latin square crossover design. The STT I was
      performed on both eyes before (baseline) and 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6,
      7, 8, and 24 hours after each injection. RESULTS: STT I values decreased
      significantly within 45 minutes after injection of medetomidine or xylazine,
      which was followed by gradual recovery. The lowest mean STT I value was < 10
      mm/min for all sedation treatments, except when dogs received 5 MUg of
      medetomidine/kg. Linear regression of the area under the curve for the 8 hours
      after administration yielded significant effects for all sedation treatments.
      CONCLUSIONS AND CLINICAL RELEVANCE: IM administration of medetomidine or xylazine
      to dogs reduced tear flow in a dose-related manner. Artificial tear solution or
      ophthalmic ointment should be used to protect the ocular surface when these drugs
      are administered to dogs.

PMID- 27027833
TI  - Effects of anesthetic induction with a benzodiazepine plus ketamine hydrochloride
      or propofol on hypothermia in dogs undergoing ovariohysterectomy.
AB  - OBJECTIVE: To assess the effect of anesthetic induction with a benzodiazepine
      plus ketamine or propofol on hypothermia in dogs undergoing ovariohysterectomy
      without heat support. ANIMALS: 23 adult sexually intact female dogs undergoing
      ovariohysterectomy. PROCEDURES: Baseline rectal temperature, heart rate, and
      respiratory rate were recorded prior to premedication with buprenorphine (0.02
      mg/kg, IM) and acepromazine (0.05 mg/kg, IM). Anesthesia was induced with
      midazolam or diazepam (0.25 mg/kg, IV) plus ketamine (5 mg/kg, IV; n = 11) or
      propofol (4 mg/kg, IV; 12) and maintained with isoflurane in oxygen. Rectal
      temperature was measured at hospital intake, prior to premedication, immediately
      after anesthetic induction, and every 5 minutes after anesthetic induction.
      Esophageal temperature was measured every 5 minutes during anesthesia, beginning
      30 minutes after anesthetic induction. After anesthesia, dogs were covered with a
      warm-air blanket and rectal temperature was measured every 10 minutes until
      normothermia (37 degrees C) was achieved. RESULTS: Dogs in both treatment groups
      had lower rectal temperatures within 5 minutes after anesthetic induction and
      throughout anesthesia. Compared with dogs that received a benzodiazepine plus
      ketamine, dogs that received a benzodiazepine plus propofol had significantly
      lower rectal temperatures and the interval from discontinuation of anesthesia to
      achievement of normothermia was significantly longer. CONCLUSIONS AND CLINICAL
      RELEVANCE: Dogs in which anesthesia was induced with a benzodiazepine plus
      propofol or ketamine became hypothermic; the extent of hypothermia was more
      profound for the propofol combination. Dogs should be provided with adequate heat
      support after induction of anesthesia, particularly when a propofol
      benzodiazepine combination is administered.

PMID- 27027834
TI  - Clinical disease and lung lesions in calves experimentally inoculated with
      Histophilus somni five days after metaphylactic administration of tildipirosin or
      tulathromycin.
AB  - OBJECTIVE: To compare clinical disease and lung lesions in calves experimentally
      inoculated with Histophilus somni 5 days after metaphylactic administration of
      tildipirosin or tulathromycin. ANIMALS Twenty-four 3-month-old Holstein and
      Holstein-crossbreed steers. PROCEDURES: Calves were randomly allocated to 3
      groups of 8 calves. On day 0, calves in group 1 received tildipirosin (4 mg/kg,
      SC), calves in group 2 received tulathromycin (2.5 mg/kg, SC), and calves in
      group 3 received isotonic saline (0.9% NaCl) solution (1 mL/45 kg, SC; control).
      On day 5, calves were inoculated with 10 mL of a solution containing H somni
      strain 7735 (1.6 * 10(9) CFUs/mL, intrabronchially; challenge). Calves were
      clinically evaluated on days 5 through 8 and euthanized on day 8. The lungs were
      grossly evaluated for evidence of pneumonia, and bronchial secretion samples
      underwent bacteriologic culture. RESULTS: The mean clinical score for each group
      was significantly increased 12 hours after challenge, compared with that
      immediately before challenge, and was significantly lower for tildipirosin
      treated calves on days 6, 7, and 8, compared with those for tulathromycin-treated
      and control calves. The mean percentage of lung consolidation for tildipirosin
      treated calves was significantly lower than those for tulathromycin-treated and
      control calves. Histophilus somni was isolated from the bronchial secretions of
      some tulathromycin-treated and control calves but was not isolated from
      tildipirosin-treated calves. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that metaphylactic administration of tildipirosin to calves 5 days
      prior to H somni challenge prevented subsequent culture of the pathogen from
      bronchial secretions and was more effective in minimizing clinical disease and
      lung lesions than was metaphylactic administration of tulathromycin.

PMID- 27027835
TI  - Evaluation of computed tomographic enterography with an orally administered
      lactulose solution in clinically normal dogs.
AB  - OBJECTIVE: To determine optimal techniques for CT enterography in clinically
      normal dogs and to evaluate luminal distention after oral administration of
      lactulose solution as a contrast agent. ANIMALS: 15 healthy dogs. PROCEDURES: CT
      was performed in a control group (2 dogs that underwent CT to evaluate metastasis
      and 5 other dogs). In a bolus administration group (5 dogs from the control
      group), lactulose solution (1.34 g/mL) was administered (60 mL/kg) rapidly via
      gastric tube to anesthetized dogs, and CT was performed every 10 minutes for 1
      hour. In a continuous administration group of 8 other dogs, lactulose solution
      (60 mL/kg) was administered slowly via nasoesophageal tube over a period of 45
      minutes. Then, 15 minutes after anesthetic induction, CT was performed every 10
      minutes for 1 hour. Luminal distention of the small intestines was evaluated
      qualitatively by use of a 3-point scale. RESULTS: All small intestinal segments
      had poor luminal distention in the control group. The terminal ileum had poor
      luminal distention for the bolus administration group. Nearly all segments had
      good luminal distention for the continuous administration group with mild adverse
      effects. Luminal distention scores from 0 to 20 minutes after lactulose
      administration were significantly higher than scores from 30 to 60 minutes.
      Interobserver reproducibility was high for all intestinal segments. CONCLUSIONS
      AND CLINICAL RELEVANCE: CT performed between 0 and 20 minutes after continuous
      administration of lactulose solution (60 mL/kg) may reveal adequate luminal
      distention for examination of small intestinal segments in dogs.

PMID- 27027836
TI  - Two-dimensional left atrium-to-aorta ratios and left ventricular M-mode
      transthoracic echocardiographic measurements in clinically normal adult
      Dachshunds.
AB  - OBJECTIVE: To estimate the left atrium-to-aorta ratio (LA:Ao) and establish 95%
      prediction intervals for left ventricular M-mode transthoracic echocardiographic
      measurements in clinically normal adult Dachshunds. ANIMALS: 40 healthy
      Dachshunds. PROCEDURES: For each dog, 3 standard 2-D echocardiographic methods
      (diameter, circumference, and cross-sectional area) were used to measure the left
      atrium and aorta and calculate the LA:Ao from right parasternal short axis (RPSA)
      images obtained at the level of the aortic valve cusps. Left ventricular M-mode
      measurements were acquired from RPSA images obtained at the chordal level
      immediately below the mitral valve. Descriptive data were generated, and the 95%
      prediction intervals were calculated by use of an allometric scaling equation and
      linear regression and compared with those calculated on the basis of data
      obtained from dogs of multiple breeds in a previous study. RESULTS: The mean (SD)
      LA:Ao was 1.40 (0.13), 2.09 (0.17), and 2.85 (0.48) for the diameter,
      circumference, and cross-sectional area methods, respectively. The 95% prediction
      intervals for the left ventricular M-mode measurements determined by an
      allometric scaling equation on the basis of Dachshund-specific data were narrower
      than those determined on the basis of data obtained from dogs of multiple breeds.
      For that allometric equation, scaling exponents on the basis of Dachshund
      specific data ranged from 0.129 to 0.397 and did not absolutely conform to the
      presumed index for linear measurements (ie, body weight(0.333)). CONCLUSIONS AND
      CLINICAL RELEVANCE: The LA:Aos and 95% prediction intervals calculated in this
      study can be used as preliminary guidelines for echocardiographic measurements of
      clinically normal Dachshunds.

PMID- 27027837
TI  - Detection and quantification of parapoxvirus DNA by use of a quantitative real
      time polymerase chain reaction assay in calves without clinical signs of
      parapoxvirus infection.
AB  - OBJECTIVE: To investigate the presence of parapoxvirus (PPV) in cattle without
      clinical signs of infection and in farm environments of PPV-infected cattle.
      ANIMALS: 28 calves without clinical signs of PPV infection on 2 farms and 11
      clinically affected calves on 6 farms. PROCEDURES: 164 oral swab samples were
      collected at regular intervals from 28 calves without clinical signs of PPV
      infection, and 11 swab samples were collected from 11 clinically affected calves.
      Viral DNA load was quantified by use of a PPV-specific quantitative real-time PCR
      (qRT-PCR) assay. RESULTS Of 28 calves without clinical signs of PPV infection, 12
      had positive results for PPV DNA by use of the qRT-PCR assay. Viral DNA was
      detected continuously over a period of 2 to 5 months from 9 of these 12 calves,
      particularly from calves with dermatomycosis or respiratory tract disease. The
      PPV DNA loads in 32 oral swab samples from these 12 calves were significantly
      lower (median, 3.2 copies/mg) than those in samples collected from the 11
      clinically affected calves (median, 3.2 * 10(4) copies/mg). Moreover, PPV DNA was
      detected in the residual feed and drinking water on both farms that housed the
      calves without clinical signs of PPV infection. CONCLUSIONS AND CLINICAL
      RELEVANCE: PPV in cattle without clinical signs of infection and in the
      environments of these cattle may represent sources of PPV transmission to
      susceptible cattle. IMPACT FOR HUMAN MEDICINE: Humans should wear gloves to
      prevent zoonotic disease transmission when handling cattle with or without
      clinical signs of PPV infection.

PMID- 27027838
TI  - Biochemical, histologic, and biomechanical characterization of native and
      decellularized flexor tendon specimens harvested from the pelvic limbs of
      orthopedically normal dogs.
AB  - OBJECTIVE: To evaluate the biochemical and biomechanical properties of native and
      decellularized superficial digital flexor tendons (SDFTs) and deep digital flexor
      tendons (DDFTs) harvested from the pelvic limbs of orthopedically normal dogs.
      SAMPLE: 22 commercially supplied tendon specimens (10 SDFT and 12 DDFT) harvested
      from the pelvic limbs of 13 canine cadavers. PROCEDURES: DNA, glycosaminoglycan,
      collagen, and protein content were measured to biochemically compare native and
      decellularized SDFT and DDFT specimens. Mechanical testing was performed on 4
      groups consisting of native tendons (5 SDFTs and 6 DDFTs) and decellularized
      tendons (5 SDFTs and 6 DDFTs). All tendons were preconditioned, and tension was
      applied to failure at 0.5 mm/s. Failure mode was video recorded for each tendon.
      Load-deformation and stress-strain curves were generated; calculations were
      performed to determine the Young modulus and stiffness. Biochemical and
      biomechanical data were statistically compared by use of the Wilcoxon rank sum
      test. RESULTS: Decellularized SDFT and DDFT specimens had significantly less DNA
      content than did native tendons. No significant differences were identified
      between native and decellularized specimens with respect to glycosaminoglycan,
      collagen, or protein content. Biomechanical comparison yielded no significant
      intra- or intergroup differences. All DDFT constructs failed at the tendon-clamp
      interface, whereas nearly half (4/10) of the SDFT constructs failed at
      midsubstance. CONCLUSIONS AND CLINICAL RELEVANCE: Decellularized commercial
      canine SDFT and DDFT specimens had similar biomechanical properties, compared
      with each other and with native tendons. The decellularization process
      significantly decreased DNA content while minimizing loss of extracellular matrix
      components. Decellularized canine flexor tendons may provide suitable,
      biocompatible graft scaffolds for bioengineering applications such as tendon or
      ligament repair.

PMID- 27027839
TI  - Development of representative magnetic resonance imaging-based atlases of the
      canine brain and evaluation of three methods for atlas-based segmentation.
AB  - OBJECTIVE: To develop representative MRI atlases of the canine brain and to
      evaluate 3 methods of atlas-based segmentation (ABS). ANIMALS: 62 dogs without
      clinical signs of epilepsy and without MRI evidence of structural brain disease.
      PROCEDURES: The MRI scans from 44 dogs were used to develop 4 templates on the
      basis of brain shape (brachycephalic, mesaticephalic, dolichocephalic, and
      combined mesaticephalic and dolichocephalic). Atlas labels were generated by
      segmenting the brain, ventricular system, hippocampal formation, and caudate
      nuclei. The MRI scans from the remaining 18 dogs were used to evaluate 3 methods
      of ABS (manual brain extraction and application of a brain shape-specific
      template [A], automatic brain extraction and application of a brain shape
      specific template [B], and manual brain extraction and application of a combined
      template [C]). The performance of each ABS method was compared by calculation of
      the Dice and Jaccard coefficients, with manual segmentation used as the gold
      standard. RESULTS: Method A had the highest mean Jaccard coefficient and was the
      most accurate ABS method assessed. Measures of overlap for ABS methods that used
      manual brain extraction (A and C) ranged from 0.75 to 0.95 and compared favorably
      with repeated measures of overlap for manual extraction, which ranged from 0.88
      to 0.97. CONCLUSIONS AND CLINICAL RELEVANCE: Atlas-based segmentation was an
      accurate and repeatable method for segmentation of canine brain structures. It
      could be performed more rapidly than manual segmentation, which should allow the
      application of computer-assisted volumetry to large data sets and clinical cases
      and facilitate neuroimaging research and disease diagnosis.

PMID- 27027840
TI  - Correction: Evaluation of autologous bone marrow-derived mesenchymal stem cells
      on renal regeneration after experimentally induced acute kidney injury in dogs.
AB  - In the report "Evaluation of autologous bone marrow-derived mesenchymal stem
      cells on renal regeneration after experimentally induced acute kidney injury in
      dogs" (Am J Vet Res 2016;77:208-217), the address for Dr. Jae-Ik Han is
      incorrect. During the first part of the study, Dr. Han was affiliated with the
      Department of Veterinary Internal Medicine, College of Veterinary Medicine,
      Konkuk University, Seoul 143- 701, South Korea. However, during the time of the
      study, Dr. Han became affiliated with the Laboratory of Wildlife Disease, College
      of Veterinary Medicine, Chonbuk National University, Iksan 54596, South Korea.
      Thus, Dr. Han's affiliation should be listed as both the Department of Veterinary
      Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 143
      701, South Korea, and the Laboratory of Wildlife Disease, College of Veterinary
      Medicine, Chonbuk National University, Iksan 54596, South Korea.

PMID- 27027841
TI  - Role of tissue factor expression in thrombin generation by canine tumor cells.
AB  - OBJECTIVE: To measure thrombin generation by high and low tissue factor (TF)
      expressing canine cancer cell lines. SAMPLE: Canine cell lines CMT25 (high TF
      expressing mammary gland tumor cell line) and HMPOS (low TF-expressing
      osteosarcoma cell line). PROCEDURES: Thrombin generation by cancer cells was
      measured in pooled normal canine plasma by use of calibrated automated
      thrombography without added trigger reagents. Results were expressed as lag time,
      time to peak thrombin concentration, peak thrombin concentration, and total
      thrombin concentration or thrombin generation potential. Corn trypsin inhibitor,
      hirudin, and annexin V were used to inhibit contact activation, thrombin
      formation, and phosphatidylserine activity, respectively. Pooled normal human
      plasma deficient in coagulation factors VII, VIII, IX, X, XI, or XII was used to
      assess the role of individual coagulation factors on thrombin generation.
      RESULTS: CMT25 generated significantly more thrombin than did HMPOS (mean +/- SD,
      3,555 +/- 604 nM thrombin*min and 636 +/- 440 nM thrombin*min, respectively).
      Thrombin generation of CMT25 was dependent on factor VII and phosphatidylserine
      and was independent of contact activation. In contrast, thrombin generation of
      HMPOS was attributed to contact activation. CONCLUSIONS AND CLINICAL RELEVANCE:
      High TF-expressing canine mammary cancer cells generated thrombin in a plasma
      milieu in vitro in a factor VII- and phosphatidylserine-dependent manner. These
      findings support a role for TF in hypercoagulability detected in dogs with
      mammary gland tumors and potentially for other tumors that strongly express TF.

PMID- 27027842
TI  - Pharmacokinetics of detomidine following intravenous or oral-transmucosal
      administration and sedative effects of the oral-transmucosal treatment in dogs.
AB  - OBJECTIVE: To determine the pharmacokinetics of detomidine hydrochloride
      administered IV (as an injectable formulation) or by the oral-transmucosal (OTM)
      route (as a gel) and assess sedative effects of the OTM treatment in healthy
      dogs. ANIMALS: 12 healthy adult dogs. PROCEDURES: In phase 1, detomidine was
      administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24
      hour washout period, each dog received the alternate treatment. Blood samples
      were collected for quantification via liquid chromatography with mass
      spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received
      dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5
      mg/m(2)), and sedation was measured by a blinded observer using 2 standardized
      sedation scales while dogs underwent jugular catheter placement. After a l-week
      washout period, each dog received the alternate treatment. RESULTS: Median
      maximum concentration, time to maximum concentration, and bioavailability for
      detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and
      34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All
      dogs were sedated and became laterally recumbent with phase 1 treatments. In
      phase 2, median global sedation score following OTM administration of detomidine
      gel was significantly lower (indicating a lesser degree of sedation) than that
      following IV dexmedetomidine treatment; however, total sedation score during
      jugular vein catheterization did not differ between treatments. The gel was
      subjectively easy to administer, and systemic absorption was sufficient for
      sedation. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine gel administered by the
      OTM route provided sedation suitable for a short, minimally invasive procedure in
      healthy dogs.

PMID- 27027843
TI  - Effects of cranberry extract on prevention of urinary tract infection in dogs and
      on adhesion of Escherichia coli to Madin-Darby canine kidney cells.
AB  - OBJECTIVE: To determine effects of cranberry extract on development of urinary
      tract infection (UTI) in dogs and on adherence of Escherichia coli to Madin-Darby
      canine kidney (MDCK) cells. ANIMALS: 12 client-owned dogs (in vivo experiment)
      and 6 client-owned dogs (in vitro experiment). PROCEDURES: 12 dogs with a history
      of recurrent UTI received an antimicrobial (n = 6) or cranberry extract (6)
      orally for 6 months. Dogs were monitored for a UTI. For the in vitro experiment,
      cranberry extract was orally administered to 6 dogs for 60 days. Voided urine
      samples were collected from each dog before and 30 and 60 days after onset of
      extract administration. Urine was evaluated by use of a bacteriostasis assay. An
      antiadhesion assay and microscopic examination were used to determine inhibition
      of bacterial adherence to MDCK cells. RESULTS: None of the 12 dogs developed a
      UTI. The bacteriostasis assay revealed no zone of inhibition for any urine
      samples. Bacterial adhesion was significantly reduced after culture with urine
      samples obtained at 30 and 60 days, compared with results for urine samples
      obtained before extract administration. Microscopic examination revealed that
      bacterial adherence to MDCK cells was significantly reduced after culture with
      urine samples obtained at 30 and 60 days, compared with results after culture
      with urine samples obtained before extract administration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Oral administration of cranberry extract prevented
      development of a UTI and prevented E coli adherence to MDCK cells, which may
      indicate it has benefit for preventing UTIs in dogs.

PMID- 27027844
TI  - A comparison of propensity score-based approaches to health service evaluation: a
      case study of a preoperative physician-led clinic for high-risk surgical
      patients.
AB  - RATIONALE, AIMS AND OBJECTIVES: A physician-led clinic for the preoperative
      optimization and management of high-risk surgical patients was implemented in a
      South Australian public hospital in 2008. This study aimed to estimate the costs
      and effects of the clinic using a mixed retrospective and prospective
      observational study design. METHOD: Alternative propensity score estimation
      methods were applied to retrospective routinely collected administrative and
      clinical data, using weighted and matched cohorts. Supplementary survey-based
      prospective data were collected to inform the analysis of the retrospective data
      and reduce potential unmeasured confounding. RESULTS: Using weighted cohorts,
      clinic patients had a significantly longer mean length of stay and higher mean
      cost. With the matched cohorts, reducing the calliper width resulted in a shorter
      mean length of stay in the clinic group, but the costs remained significantly
      higher. The prospective data indicated potential unmeasured confounding in all
      analyses other than in the most tightly matched cohorts. CONCLUSIONS: The
      application of alternative propensity-based approaches to a large sample of
      retrospective data, supplemented with a smaller sample of prospective data,
      informed a pragmatic approach to reducing potential observed and unmeasured
      confounding in an evaluation of a physician-led preoperative clinic. The need to
      generate tightly matched cohorts to reduce the potential for unmeasured
      confounding indicates that significant uncertainty remains around the effects of
      the clinic. This study illustrates the value of mixed retrospective and
      prospective observational study designs but also underlines the need to
      prospectively plan for the evaluation of costs and effects alongside the
      implementation of significant service innovations.

PMID- 27027845
TI  - Refinement of the Nanoparticle Emission Assessment Technique into the
      Nanomaterial Exposure Assessment Technique (NEAT 2.0).
AB  - Engineered nanomaterial emission and exposure characterization studies have been
      completed at more than 60 different facilities by the National Institute for
      Occupational Safety and Health (NIOSH). These experiences have provided NIOSH the
      opportunity to refine an earlier published technique, the Nanoparticle Emission
      Assessment Technique (NEAT 1.0), into a more comprehensive technique for
      assessing worker and workplace exposures to engineered nanomaterials. This change
      is reflected in the new name Nanomaterial Exposure Assessment Technique (NEAT
      2.0) which distinguishes it from NEAT 1.0. NEAT 2.0 places a stronger emphasis on
      time-integrated, filter-based sampling (i.e., elemental mass analysis and
      particle morphology) in the worker's breathing zone (full shift and task
      specific) and area samples to develop job exposure matrices. NEAT 2.0 includes a
      comprehensive assessment of emissions at processes and job tasks, using direct
      reading instruments (i.e., particle counters) in data-logging mode to better
      understand peak emission periods. Evaluation of worker practices, ventilation
      efficacy, and other engineering exposure control systems and risk management
      strategies serve to allow for a comprehensive exposure assessment.

PMID- 27027846
TI  - Rapid increase of serum anti-MDA-5 antibodies and exacerbation of clinically
      amyopathic dermatomyositis/interstitial lung disease.

PMID- 27027847
TI  - A randomized controlled trial of the ketogenic diet in refractory childhood
      epilepsy.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of the ketogenic diet (KD)
      during the first 4 months of a randomized controlled trial (RCT) in refractory
      epilepsy patients aged 1-18 years. METHODS: Children and adolescents with
      refractory epilepsy, not eligible for epilepsy surgery, were included. Following
      1 month at baseline, patients were randomized to either the KD or to care as
      usual (CAU).Primary outcome is the proportion of patients with at least 50%
      reduction in seizure frequency at 4 months. Secondary outcomes are mean
      percentage of baseline seizures, seizure severity, and side effects. RESULTS:
      Fifty-seven patients were randomized; nine dropped out, leaving 48 for analysis
      (i.e., 26 KD, 22 CAU). In an intention-to-treat analysis, 13 patients (50%)
      treated with the KD and four patients (18.2%) of the CAU group were
      responders.Mean seizure frequency at 4 months compared to baseline, after removal
      of two outliers in the KD group, was significantly lower (P = 0.024) in the KD
      group (56%) (95% CI: 36-76) than in the CAU group (99%) (95% CI: 65-133%).Twice
      as many patients in the KD group had a relevant decrease in seizure severity
      score (P = 0.070).Patients treated with the KD had a significantly higher score
      for gastrointestinal symptoms (P = 0.021) without an increase in the total score
      of side effects. CONCLUSIONS: This trial provides class I evidence that the KD is
      an effective therapy in children and adolescents with refractory epilepsy
      compared with CAU. Most often reported side effects are gastrointestinal
      symptoms.The study has been registered with the Netherlands Trial Registry
      (NTR2498).

PMID- 27027848
TI  - Ethical considerations in preventive interventions for bipolar disorder.
AB  - AIM: Early intervention and prevention of serious mental disorders such as
      bipolar disorder has the promise of decreasing the burden associated with these
      disorders. With increasing early and preventive intervention efforts among
      cohorts such as those with a familial risk for bipolar disorder, there is a need
      to examine the associated ethical concerns. The aim of this review was to examine
      the ethical issues underpinning the clinical research on pre-onset identification
      and preventive interventions for bipolar disorder. METHODS: We undertook a PubMed
      search updated to November 2014 incorporating search terms such as bipolar,
      mania, hypomania, ethic*(truncated), early intervention, prevention, genetic and
      family. RESULTS: Fifty-six articles that were identified by this method as well
      as other relevant articles were examined within a framework of ethical principles
      including beneficence, non-maleficence, respect for autonomy and justice. The
      primary risks associated with research and clinical interventions include stigma
      and labelling, especially among familial high-risk youth. Side effects from
      interventions are another concern. The benefits of preventive or early
      interventions were in the amelioration of symptoms as well as the possibility of
      minimizing disability, cognitive impairment and progression of the illness.
      Supporting the autonomy of individuals and improving access to stigma-free care
      may help moderate the potential challenges associated with the risks of
      interventions. CONCLUSIONS: Concerns about the risks of early identification and
      pre-onset interventions should be balanced against the potential benefits, the
      individuals' right to choice and by improving availability of services that
      balance such dilemmas.

PMID- 27027849
TI  - Mixed-mode chromatography integrated with high-performance liquid chromatography
      for protein analysis and separation: Using bovine serum albumin and lysozyme as
      the model target.
AB  - A type of mixed-mode chromatography was integrated with high-performance liquid
      chromatography for protein analysis and separation. The chromatographic behavior
      was tested using bovine serum albumin and lysozyme as model proteins. For the
      mixed-mode column, the silica beads were activated with gamma-(2,3-epoxypropoxy)
      propytrimethoxysilane and coupled with 4-mercaptopyridine as the functional
      ligand. The effects of pH, salt, and the organic solvent conditions of the mobile
      phase on the retention behavior were studied, which provided valuable clues for
      separation strategy. When eluted with a suitable pH gradient, salt concentration
      gradient, and acetonitrile content gradient, the separation behavior of bovine
      serum albumin and lysozyme could be controlled by altering the conditions of the
      mobile phase. The results indicated this type of chromatography might be a useful
      method for protein analysis and separation. 

PMID- 27027850
TI  - Corrigendum: Precursor and mature NGF live tracking: one versus many at a time in
      the axons.

PMID- 27027851
TI  - Systematic review of antibiotic treatment for acute calculous cholecystitis.
AB  - BACKGROUND: Intravenous antibiotics are frequently used in the initial management
      of acute calculous cholecystitis (ACC), although supportive care alone preceding
      delayed elective cholecystectomy may be sufficient. This systematic review
      assessed the success rate of antibiotics in the treatment of ACC. METHODS: A
      systematic search of MEDLINE, Embase and Cochrane Library databases was
      performed. Primary outcomes were the need for emergency intervention and
      recurrence of ACC after initial non-operative management of ACC. Risk of bias was
      assessed. Pooled event rates were calculated using a random-effects model.
      RESULTS: Twelve randomized trials, four prospective and ten retrospective studies
      were included. Only one trial including 84 patients compared treatment with
      antibiotics to that with no antibiotics; there was no significant difference
      between the two groups in terms of length of hospital stay and morbidity. Some
      5830 patients with ACC were included, of whom 2997 had early cholecystectomy,
      2791 received initial antibiotic treatment, and 42 were treated conservatively.
      Risk of bias was high in most studies, and all but three studies had a low level
      of evidence. For randomized studies, pooled event rates were 15 (95 per cent c.i.
      10 to 22) per cent for the need for emergency intervention and 10 (5 to 20) per
      cent for recurrence of ACC. The pooled event rate for both outcomes combined was
      20 (13 to 30) per cent. CONCLUSION: Antibiotics are not indicated for the
      conservative management of ACC or in patients scheduled for cholecystectomy.

PMID- 27027853
TI  - Stereoretentive Addition of N-tert-Butylsulfonyl-alpha-Amido Silanes to
      Aldehydes, Ketones, alpha,beta-Unsaturated Esters, and Imines.
AB  - Enantioenriched N-tert-butylsulfonyl-alpha-amido silanes were successfully
      reacted with aldehydes, ketones, imines, and alpha,beta-unsaturated esters in the
      presence of a sub-stoichiometric amount of CsF (0.5 equiv) in 1,2-dimethoxyethane
      (DME) at -20  degrees C to afford the corresponding coupling products with up to
      89 % enantiospecificity in a retentive manner.

PMID- 27027854
TI  - Deploying an Ecological Model to Stem the Rising Tide of Firearm Suicide in Older
      Age.
AB  - A central objective of the Surgeon General's National Strategy for Suicide
      Prevention is to focus on older adults. We review individual risk-factors for
      suicide in late life and then introduce an ecological model to expand
      conceptualization of elder suicide. We first look at the role of firearms,
      providing evidence that firearm availability increases the means of elder suicide
      and gun access policies can contribute to reducing risk. Next, we focus on
      primary care providers, documenting how older adults often come into contact with
      these professionals before ending their lives and how these providers could take
      a more active role in mediating individual-level risk factors. We then turn our
      attention to the intersection between gun access and primary care and consider
      how advancing standards of care concerning gun access and suicide risk might be
      an effective policy alternative for blocking the pathway to suicide among older
      adults. 

PMID- 27027855
TI  - Fabrication and in vivo evaluation of an osteoblast-conditioned nano
      hydroxyapatite/gelatin composite scaffold for bone tissue regeneration.
AB  - In this study, the effects of osteoblast-conditioning on mechanical behavior,
      biocompatibility, biodegradation and osteoinductive properties of a nano
      hydroxyapatite/gelatin (HA/GEL) nanocomposite scaffold was investigated. The
      scaffold was fabricated using the layer solvent casting combined with the freeze
      drying and lamination techniques. The scaffolds were conditioned by culture of
      osteoblasts on their surface and their elimination by a repeated freeze-thawing
      process. The potential of the osteoblast-conditioned HA/GEL (HA/GEL/OC) scaffold
      to support cell adhesion and growth and its cytotoxicity was assessed in vitro
      using rat mesenchymal stem cells. For in vivo studies, the HA/GEL/OC
      nanocomposite was implanted in the critical size bone defect created on rat
      calvarium and studied after 7, 30 and 90 days. The results showed that mechanical
      and in vitro biological properties of the scaffold were not affected by the
      process of conditioning. However, in vivo studies demonstrated that osteoblast
      conditioning enhanced biocompatibility and osteoinductivity and of the
      nanocomposite scaffold. The osteoblast conditioning also accelerated collagen
      content during the bone healing. In the experimental group that received the
      HA/GEL/OC and MSCs, the newly formed bone occupied almost the entire defect (93.4
      +/- 3.3%) within 3 months. In conclusion, this study indicates that osteoblast
      conditioning is a viable strategy for the development of bone tissue engineering
      scaffolds. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2001
      2010, 2016.

PMID- 27027856
TI  - Rapid Device-Detected Nonsustained Ventricular Tachycardia in the Risk
      Stratification of Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: Nonsustained ventricular tachycardia (NSVT) detected by ambulatory
      Holter (Holter NSVT) is a major risk factor for sudden cardiac death in
      hypertrophic cardiomyopathy (HCM). We hypothesized that the prognostic utility of
      Holter NSVT in HCM would improve with prolonged monitoring and a higher heart
      rate cut-off for detection. METHODS: We enrolled 60 patients (44 +/- 14 years)
      with HCM, who had a prophylactic implantable cardioverter defibrillator (ICD).
      Positive Holter NSVT (prior to implant) was defined as >=3 beats at >=120 beats
      per minute (bpm). We assessed the prevalence of rapid NSVT (RNSVT) detected by
      their ICD within 12 months of its implant, defined as 4-16 beats at >=150-200
      bpm. The primary outcome was appropriate ICD therapy (antitachycardia pacing and
      shocks) for sustained ventricular arrhythmia (VA). RESULTS: Holter NSVT was
      detected in 34 patients. RNSVT occurred in 21 (35%) patients of whom five did not
      have Holter NSVT. Over a median follow-up of 61 (interquartile range 29, 129)
      months after ICD implant, nine patients had VA. RNSVT, but not Holter NSVT, was
      significantly associated with VA (hazard ratio 6.2, 95% confidence interval [1.3
      30], P = 0.01) by multivariable Cox regression analysis that included
      conventional risk factors. Receiver operating characteristic analysis for RNSVT
      (area under curve 0.80, P = 0.005) showed that the occurrence of >=2 episodes of
      RNSVT discriminated patients for VA optimally (sensitivity 78%, specificity 84%,
      positive predictive value 47%, negative predictive value 96%). CONCLUSIONS: In
      this pilot study, RNSVT detected by continuous monitoring independently predicted
      VA in HCM and offered superior discrimination of VA risk compared to conventional
      risk factors, including Holter NSVT. Future studies are needed to validate these
      findings in a larger, unselected HCM cohort.

PMID- 27027857
TI  - Receiving Hospital Characteristics Associated With Survival in Patients
      Transported by Emergency Medical Services After Out-of-hospital Cardiac Arrest.
AB  - OBJECTIVE: To test whether primary emergency medical services (EMS) transport to
      hospitals with certain characteristics (24/7 percutaneous coronary intervention
      [PCI] availability, trauma center status, large [>24 bed] intensive care unit
      [ICU]) versus hospitals without those characteristics is associated with improved
      hospital survival after out-of-hospital cardiac arrest (OHCA). METHODS: This is
      an analysis of a prospectively collected EMS database, which archives patients
      with OHCA treated by a single large metropolitan EMS system. The database
      contains Utstein data, EMS transport data, and survival to hospital discharge.
      EMS providers uniformly apply advanced cardiac life support protocols to OHCA
      patients in the field. Patients with return of spontaneous circulation (ROSC) are
      transported to one of 10 hospitals in the area. If ROSC is not achieved within 30
      minutes, efforts are terminated and the patient is not transported. We used
      multivariate logistic regression to test if receiving hospital characteristics
      were independently associated with survival among those transported after ROSC.
      We excluded patients not transported to a hospital and patients with incomplete
      outcome data. RESULTS: Between January 2011 and December 2014, a total of 1,188
      OHCA patients were resuscitated in the field and transported to an area hospital.
      After patients with missing data were excluded, 1,024 patients were included in
      the analysis. The mean (+/-SD) age was 61.1 (+/-17.0) years, and 57.7% were male.
      Of transported patients, 76% were taken to 24/7 PCI centers, 46% were taken to
      trauma centers, and 37% were taken to hospitals with large ICUs. There was
      considerable overlap in these hospital characteristics. A multivariate logistic
      regression model including age, sex, shockable rhythm, EMS time to scene, and
      dispatch complaint of cardiac arrest found that none of the hospital
      characteristics were independently associated with increased survival to
      discharge. The odds ratios (95% confidence intervals) for survival were as
      follows: PCI center, 1.28 (0.80 to 2.04); trauma center, 1.44 (0.73 to 2.85); and
      large ICU, 1.39 (0.69 to 2.80). CONCLUSIONS: After adjusting for patient
      demographic data, we found no significant independent association between
      receiving hospital characteristics and survival to discharge among OHCA patients
      transported after ROSC by a single EMS agency.

PMID- 27027858
TI  - Targeting the untargetable? Nodal expression in TNBC.

PMID- 27027859
TI  - Age differences in conditioned place preferences and taste aversions to nicotine.
AB  - Adolescents and adults differ in their behavioral sensitivities to drugs of
      abuse, including nicotine. Studies have shown that both rewarding and aversive
      properties of drugs of abuse can exist concomitantly. The present study
      investigated the ontogeny of these opposing qualities across a range of doses
      using a combined conditioned taste aversion and place preference paradigm in pair
      housed rats that were not deprived of food or water. Results indicated that
      adolescents were more sensitive to the rewarding properties of nicotine than
      adults. In contrast, although all doses produced a taste aversion at both ages in
      the same rats, the aversion was weaker at lower than high doses in adolescents
      whereas adults showed strong aversion at all doses, suggesting modest attenuation
      in nicotine's aversive properties among adolescents relative to adults. Thus,
      attenuated aversive and accented appetitive sensitivities of adolescents to
      nicotine can be experienced simultaneously in the same animals. (c) 2016 Wiley
      Periodicals, Inc. Dev Psychobiol 58: 660-666, 2016.

PMID- 27027860
TI  - Antibody-mediated inhibition of Nogo-A signaling promotes neurite growth in PC-12
      cells.
AB  - The use of a monoclonal antibody to block the neurite outgrowth inhibitor Nogo-A
      has been of great interest for promoting axonal recovery as a treatment for
      spinal cord injury. While several cellular and non-cellular assays have been
      developed to quantify the bioactive effects of Nogo-A signaling, demand still
      exists for the development of a reliable approach to characterize the
      effectiveness of the anti-Nogo-A antibody. In this study, we developed and
      validated a novel cell-based approach to facilitate the biological quantification
      of a Nogo-A antibody using PC-12 cells as an in vitro neuronal cell model.
      Changes in the mRNA levels of the neuronal differentiation markers, growth
      associated protein 43 and neurofilament light-polypeptide, suggest that
      activation of the Nogo-A pathway suppresses axonal growth and dendrite formation
      in the tested cell line. We found that application of anti-Nogo-A monoclonal
      antibody can significantly enhance the neuronal maturity of PC-12 cells by
      blocking the Nogo-A inhibitory effects, providing enhanced effects on neural
      maturity at the molecular level. No adverse effects were observed on cell
      viability. 

PMID- 27027861
TI  - New Copper, Palladium and Nickel Catalytic Systems: An Evolution towards More
      Efficient Procedures.
AB  - Metal-catalysed reactions are a fundamental tool in synthetic chemistry.
      Increasingly challenging transformations can be accomplished only by means of
      certain metal catalysts. However, there still remains the need for a substantial
      decrease of the amount of catalyst, for better reuse or recycling of such active
      species, and for the avoidance of relatively toxic solvents in favour of
      environmentally friendly media. These facts apply to copper-, palladium-, and
      nickel-catalysed cross-coupling reactions, direct arylations, and oxidative
      processes. This account summarises our research on the last reactions, featuring
      an evolution towards more sustainable procedures in this field.

PMID- 27027862
TI  - No objectively measured sleep disturbances in children with attention
      deficit/hyperactivity disorder.
AB  - The main goal of this study was to gain more insight into sleep disturbances in
      children with attention-deficit/hyperactivity disorder, using objective measures
      of sleep quality and quantity. The evidence for sleep problems in children with
      attention-deficit/hyperactivity disorder thus far is inconsistent, which might be
      explained by confounding influences of comorbid internalizing and externalizing
      problems and low socio-economic status. We therefore investigated the mediating
      and moderating role of these factors in the association between attention
      deficit/hyperactivity disorder and sleep problems. To control for the effects of
      stimulant medication use, all participants were tested free of medication. Sixty
      three children with attention-deficit/hyperactivity disorder and 61 typically
      developing children, aged 6-13 years, participated. Sleep was monitored for one
      to three school nights using actigraphy. Parent and teacher questionnaires
      assessed symptoms of attention-deficit/hyperactivity disorder, internalizing
      behaviour, oppositional defiant disorder and conduct disorder. Results showed no
      differences between the attention-deficit/hyperactivity disorder and typically
      developing group in any sleep parameter. Within the attention
      deficit/hyperactivity disorder group, severity of attention-deficit/hyperactivity
      disorder symptoms was not related to sleep quality or quantity. Moderation
      analyses in the attention-deficit/hyperactivity disorder group showed an
      interaction effect between attention-deficit/hyperactivity disorder symptoms and
      internalizing and externalizing behaviour on total sleep time, time in bed and
      average sleep bout duration. The results of our study suggest that having
      attention-deficit/hyperactivity disorder is not a risk factor for sleep problems.
      Internalizing and externalizing behaviour moderate the association between
      attention-deficit/hyperactivity disorder and sleep, indicating a complex
      interplay between psychiatric symptoms and sleep.

PMID- 27027863
TI  - Angiographic and volumetric effects of mammalian target of rapamycin inhibitors
      on angiomyolipomas in tuberous sclerosis.
AB  - AIM: To investigate the angiographic and volumetric effects of mammalian target
      of rapamycin (mTOR) inhibitors on angiomyolipomas (AMLs) in a case series of
      patients with tuberous sclerosis complex. METHODS: All patients who underwent
      catheter angiography prior to and following mTOR inhibitor therapy (n = 3) were
      evaluated. All cross-sectional imaging studies were analyzed with three
      dimensional volumetrics, and tumor volume curves for all three tissue
      compartments (soft tissue, vascular, and fat) were generated. Segmentation
      analysis tools were used to automatically create a region of interest (ROI)
      circumscribing the AML. On magnetic resonance images, the "fat only" map
      calculated from the in- and opposed-phase gradient recalled echo sequences was
      used to quantify fat volume within tumors. Tumor vascularity was measured by
      applying a thresholding tool within the ROI on post-contrast subtraction images.
      On computed tomography images, volume histogram analysis of Hounsfield unit was
      performed to quantify tumor tissue composition. The angiography procedures were
      also reviewed, and tumor vascularity based on pre-embolization angiography was
      characterized in a semi-quantitative manner. RESULTS: Patient 1 presented at the
      age of 15 with a 6.8 cm right lower pole AML and a 4.0 cm right upper pole AML.
      Embolization was performed of both tumors, and after a few years of size control,
      the tumors began to grow, and the patient was initiated on mTOR inhibitor
      therapy. There was an immediate reduction in the size of both lesions. The
      patient then underwent repeat embolization and discontinuation of mTOR
      inhibition, after which point there was a substantial regrowth in both tumors
      across all tissue compartments. Patient 2 presented at the age of 18 with a right
      renal AML. Following a brief period of tumor reduction after embolization, she
      was initiated on mTOR inhibitor therapy, with successful reduction in tumor size
      across all tissue compartments. As with patient 1, however, there was immediate
      rebound growth following discontinuation of inhibitor therapy, without sustained
      control despite repeat embolization. patient 3 presented at the age of 5 with a
      left renal AML and underwent two embolization procedures without lasting effect
      prior to starting mTOR inhibition. As with patients 1 and 2, following
      discontinuation of therapy, there was immediate rebound growth of the tumor.
      Repeat embolization, however, was notable for a substantial reduction in
      intratumoral aneurysms and vascularity. CONCLUSION: AML volume reduction as well
      as post-treatment rebound growth due to mTOR inhibitors involves all three tissue
      components of the tumor.

PMID- 27027864
TI  - Effect of occlusal vertical dimension on swallowing patterns and perioral
      electromyographic activity.
AB  - Abnormal swallow patterns have been associated with specific dentofacial traits,
      such as an anterior open bite, but the cause-effect relationship between
      swallowing and malocclusion remains highly controversial. The aim of this
      research was to determine the effects of acute change in occlusal vertical
      dimension (OVD) on intraoral pressure swallow patterns and perioral
      electromyographic activity (EMG) during swallowing. Ten volunteers (five female,
      five male; 27-32 years) repeated standardised swallowing tasks as the OVD was
      progressively increased using mandibular trays of different heights. Standardised
      swallowing tasks were performed repetitively with each tray in place. Individual
      swallowing waveforms were quantitatively and qualitatively analysed. Peak
      pressure, swallow duration, time to peak pressure and lip EMG peak activity were
      assessed for each swallow. Data were analysed using mixed-model analysis. As OVD
      increased, lip peak pressure during swallowing increased almost threefold (+2.1
      kPa; P <= 0.001), whereas swallow duration increased by 12.7 per cent (+160 ms; P
      = 0.01) at lip level and by 26.4 per cent (+270 ms; P < 0.001) at tongue level.
      Perioral muscle activity during swallows increased by 43.7 per cent (P <= 0.01)
      up to the OVD where resting lip seal was not attainable. Swallowing waveforms
      varied markedly between individuals, but interindividual waveforms were only
      minimally affected. The adaptive response and the waveform similarities
      associated with OVD variation supports the existence of a central control
      mechanism for swallowing, which may be modified by peripheral inputs. 

PMID- 27027865
TI  - Effects of ageing and physical activity on blood pressure and endothelial
      function during acute inflammation.
AB  - NEW FINDINGS: What is the central question of this study? Do older and younger
      adults have similar vascular endothelial and blood pressure responses to acute
      inflammation? Does physical activity affect these responses? What is the main
      finding and its importance? Older adults reduce blood pressure whereas younger
      adults reduce endothelial function during acute inflammation. Physical activity
      does not provide protection against these inflammation-induced changes. This is
      important because older adults regularly experience acute increases in systemic
      inflammation that may predispose older adults to cardiovascular events through
      dysregulation of blood pressure. Ageing is characterized by chronic, low-grade
      inflammation that is related to endothelial dysfunction and arterial stiffness.
      Physical activity can protect older adults (OAs) from cardiovascular dysfunction
      and increased inflammation. Acute inflammation causes transient endothelial
      dysfunction and arterial stiffening in younger adults (YAs), but may not have the
      same effect in OAs. We hypothesized that acute inflammation would increase blood
      pressure (BP) and endothelial impairment to a greater extent in OAs versus YAs,
      but that physical activity would be protective. We induced inflammation with an
      influenza vaccine in 22 OAs (55-75 years old) and 31 YAs (18-35 years old) and
      measured brachial flow-mediated dilatation (FMD), BP and serum inflammatory
      markers before vaccination and at 24 and 48 h afterwards. Physical activity data
      were collected using accelerometry. During inflammation, only OAs reduced
      systolic BP (from 120 +/- 3 to 115 +/- 2 to 115 +/- 3 mmHg, P < 0.05), but only
      YAs reduced FMD (from 11.3 +/- 0.7 to 8.5 +/- 0.6 to 8.9 +/- 0.6% in YAs and from
      6.7 +/- 0.6 to 5.3 +/- 0.7 to 6.0 +/- 0.6% in OAs, P < 0.05 for time and
      interaction effects). The entire cohort increased C-reactive protein (P < 0.05),
      but only YAs increased interleukin-6 (P < 0.05 for time * age group interaction).
      Physical activity was related to the percentage change in inflammation in OAs (r
      = -0.50, P < 0.05) but not to the change in arterial function in either group (P
      > 0.05 for all). We conclude that acute inflammation reduced FMD only in YAs and
      reduced BP only in OAs. Physical activity did not affect arterial function during
      acute inflammation. Clinicians should be aware that all OAs are vulnerable to
      inflammation-mediated reductions in BP and cardiovascular complications.

PMID- 27027866
TI  - Characterization of photomorphogenic responses and signaling cascades controlled
      by phytochrome-A expressed in different tissues.
AB  - The photoreceptor phytochrome A acts as a light-dependent molecular switch and
      regulates responses initiated by very low fluences of light (VLFR) and high
      fluences (HIR) of far-red light. PhyA is expressed ubiquitously, but how phyA
      signaling is orchestrated to regulate photomorphogenesis is poorly understood. To
      address this issue, we generated transgenic Arabidopsis thaliana phyA-201 mutant
      lines expressing the biologically active phyA-YFP photoreceptor in different
      tissues, and analyzed the expression of several reporter genes, including
      ProHY5:HY5-GFP and Pro35S:CFP-PIF1, and various FR-HIR-dependent physiological
      responses. We show that phyA action in one tissue is critical and sufficient to
      regulate flowering time and root growth; control of cotyledon and hypocotyl
      growth requires simultaneous phyA activity in different tissues; and changes
      detected in the expression of reporters are not restricted to phyA-containing
      cells. We conclude that FR-HIR-controlled morphogenesis in Arabidopsis is
      mediated partly by tissue-specific and partly by intercellular signaling
      initiated by phyA. Intercellular signaling is critical for many FR-HIR induced
      responses, yet it appears that phyA modulates the abundance and activity of key
      regulatory transcription factors in a tissue-autonomous fashion.

PMID- 27027867
TI  - Monocyte activation and cytokine production in Malawian children presenting with
      P. falciparum malaria.
AB  - Malaria in malaria-naive adults is associated with an inflammatory response
      characterized by expression of specific activation markers on innate immune
      cells. Here, we investigate activation and adhesion marker expression, and
      cytokine production in monocytes from children presenting with cerebral malaria
      (CM, n = 36), severe malarial anaemia (SMA, n = 42) or uncomplicated malaria (UM,
      n = 66), and healthy aparasitemic children (n = 52) in Blantyre, Malawi. In all
      malaria groups, but particularly in the two severe malaria groups, monocyte
      expression of CD11b, CD11c, CD18, HLA-DR and CD86, and percentages of TNF-alpha-
      and IL-6-producing monocytes were lower than in healthy controls, while
      expression of CD11a, TLR2 and TLR4 was lower in children with severe malaria
      compared with controls. These levels mostly normalized during convalescence, but
      percentages of cytokine-producing monocytes remained suppressed in children with
      SMA. In all malaria groups, especially the SMA group, a greater proportion of
      monocytes were loaded with haemozoin than among controls. In a P. falciparum
      hyperendemic area, monocytes in children with acute symptomatic malaria have
      reduced expression of adhesion molecules and activation markers and reduced
      inflammatory cytokine production. This immune suppression could be due to
      accumulation of haemozoin and/or previous exposure to P. falciparum.

PMID- 27027868
TI  - Linking field-based metabolomics and chemical analyses to prioritize contaminants
      of emerging concern in the Great Lakes basin.
AB  - The ability to focus on the most biologically relevant contaminants affecting
      aquatic ecosystems can be challenging because toxicity-assessment programs have
      not kept pace with the growing number of contaminants requiring testing. Because
      it has proven effective at assessing the biological impacts of potentially toxic
      contaminants, profiling of endogenous metabolites (metabolomics) may help screen
      out contaminants with a lower likelihood of eliciting biological impacts, thereby
      prioritizing the most biologically important contaminants. The authors present
      results from a study that utilized cage-deployed fathead minnows (Pimephales
      promelas) at 18 sites across the Great Lakes basin. They measured water
      temperature and contaminant concentrations in water samples (132 contaminants
      targeted, 86 detected) and used 1 H-nuclear magnetic resonance spectroscopy to
      measure endogenous metabolites in polar extracts of livers. They used partial
      least-squares regression to compare relative abundances of endogenous metabolites
      with contaminant concentrations and temperature. The results indicated that
      profiles of endogenous polar metabolites covaried with at most 49 contaminants.
      The authors identified up to 52% of detected contaminants as not significantly
      covarying with changes in endogenous metabolites, suggesting they likely were not
      eliciting measurable impacts at these sites. This represents a first step in
      screening for the biological relevance of detected contaminants by shortening
      lists of contaminants potentially affecting these sites. Such information may
      allow risk assessors to prioritize contaminants and focus toxicity testing on the
      most biologically relevant contaminants. Environ Toxicol Chem 2016;35:2493-2502.
      Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US
      Government work and, as such, is in the public domain in the United States of
      America.

PMID- 27027869
TI  - Disentangling the effects of race and socioeconomic factors on liver
      transplantation rates for hepatocellular carcinoma.
AB  - INTRODUCTION: Liver transplantation is the most effective treatment for
      hepatocellular carcinoma (HCC) in eligible patients, but is not accessed equally
      by all. We explored the effects of race and socioeconomic factors on
      transplantation for HCC while controlling for stage, resection status, and
      transplant candidacy. PATIENTS AND METHODS: All HCC patients, 2003-2013, were
      retrospectively analyzed using multivariate analysis to explore differences in
      transplantation rates among cohorts. RESULTS: Of 3078 HCC patients, 754 (24%)
      were considered transplant eligible. Odds of transplantation were significantly
      higher for those with commercial insurance (OR = 1.99, 95% CI [1.42, 2.79]) and
      lower for black patients (OR = 0.55, 95% CI [0.33, 0.91]). Asians were more
      likely to be resected than white patients with similarly staged tumors and
      transplant criteria (p < 0.001). Patients not listed for transplantation for non
      medical reasons were more likely to be government-insured (p = 0.02) and not
      white (p = 0.05). No step along the transplantation pathway was identified as the
      dominant hurdle. DISCUSSION: Patients who are black or government-insured are
      significantly less likely to undergo transplantation for HCC despite controlling
      for tumor stage, resection status, and transplant eligibility. Asian patients
      have higher rates of hepatic resection, but also appear to have lower
      transplantation rates beyond this effect.

PMID- 27027870
TI  - Unearthing the Fossorial Tadpoles of the Indian Dancing Frog Family Micrixalidae.
AB  - Tadpoles of the monotypic Indian dancing frog family Micrixalidae have remained
      obscure for over 125 years. Here we report the discovery of the elusive tadpoles
      of Micrixalus herrei from the sand beds of a forested stream in southern Western
      Ghats, and confirm their identity through DNA barcoding. These actively burrowing
      tadpoles lead an entirely fossorial life from eggs to late metamorphic stages. We
      describe their internal and external morphological characters while highlighting
      the following features: eel-like appearance, extensively muscularized body and
      tail, reduced tail fins, skin-covered eyes, delayed development of eye
      pigmentation in early pre-metamorphic stages (Gosner stages 25-29), prominent
      tubular sinistral spiracle, large transverse processes on vertebrae II and III,
      ankylosed ribs on transverse processes of vertebra II, notochord terminating
      before the atlantal cotyle-occipital condyle junction, absence of keratodonts,
      serrated well-formed jaw sheaths, and extensive calcified endolymphatic sacs
      reaching sacrum posteriorly. The tadpole gut contains mostly fine sediments and
      sand. We discuss the eel-like morphology and feeding habits of M. herrei in the
      context of convergence with other well-known fossorial tadpoles. This discovery
      builds the knowledge base for further comparative analyses and conservation of
      Micrixalus, an ancient and endemic lineage of Indian frogs. 

PMID- 27027871
TI  - Linking Measures of Colony and Individual Honey Bee Health to Survival among
      Apiaries Exposed to Varying Agricultural Land Use.
AB  - We previously characterized and quantified the influence of land use on survival
      and productivity of colonies positioned in six apiaries and found that colonies
      in apiaries surrounded by more land in uncultivated forage experienced greater
      annual survival, and generally more honey production. Here, detailed metrics of
      honey bee health were assessed over three years in colonies positioned in the
      same six apiaries. The colonies were located in North Dakota during the summer
      months and were transported to California for almond pollination every winter.
      Our aim was to identify relationships among measures of colony and individual bee
      health that impacted and predicted overwintering survival of colonies. We tested
      the hypothesis that colonies in apiaries surrounded by more favorable land use
      conditions would experience improved health. We modeled colony and individual bee
      health indices at a critical time point (autumn, prior to overwintering) and
      related them to eventual spring survival for California almond pollination.
      Colony measures that predicted overwintering apiary survival included the amount
      of pollen collected, brood production, and Varroa destructor mite levels. At the
      individual bee level, expression of vitellogenin, defensin1, and lysozyme2 were
      important markers of overwinter survival. This study is a novel first step toward
      identifying pertinent physiological responses in honey bees that result from
      their positioning near varying landscape features in intensive agricultural
      environments. 

PMID- 27027872
TI  - What does the mean menarcheal age mean?-An analysis of temporal pattern in
      variability in a historical swiss population from the 19th and 20th centuries.
AB  - OBJECTIVES: Age at menarche is one of the most important factors when observing
      growth and development. The aim of this study was to assess the temporal pattern
      in variability of menarcheal age for a historic Swiss population from the 19th
      and 20th centuries. METHODS: Medical health records from the Bernese women's
      hospital (Switzerland) were analyzed. From 10,081 women of a historical Swiss
      population (born from 1815 to 1954), menarcheal age was calculated. A possible
      decline in average menarcheal age and variance and skewness were analyzed with
      the use of descriptive statistics, generalized additive models, and correlation.
      RESULTS: Mean menarcheal age declined from 17.34 years (n = 358) around 1830 to
      13.80 years (n = 141) around 1950. Within-cohort variance decreased from 7.5 to
      2.1 year(2) . Skewness was negatively correlated with birth year (r = -0.58).
      CONCLUSION: This study provided evidence for a secular trend in various
      statistical parameters for age at menarche since the 19th century. Furthermore,
      the results of the analysis of temporal pattern in variability revealed that the
      secular trend in menarcheal age happened in two phases. Am. J. Hum. Biol. 28:705
      713, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27027873
TI  - Long-term follow-up after PFO device closure: Outcomes and Complications in a
      Single-center Experience.
AB  - OBJECTIVES: To describe medium- to long-term follow-up of patients undergoing
      device closure of patent foramen ovale (PFO) for stroke or transient ischemic
      attack (TIA). BACKGROUND: Transcatheter device closure of PFO continues to be
      used for secondary prevention of cryptogenic stroke or TIA, but data are lacking
      regarding long-term outcomes. METHODS: We reviewed the Mayo Clinic Rochester PFO
      database for patients who underwent device closure of PFO for secondary
      prevention of stroke/TIA from December 2001 to June 2012. Demographic, clinical,
      procedural, and follow-up data were reviewed. Recurrence rate of stroke/TIA were
      calculated. Data were analyzed to identify risk factors of recurrent neurologic
      events. RESULTS: Seven hundred and thirty patients (mean age 53 years; 40%
      female) were included in our study. Most patients (72%) had cryptogenic stroke as
      their qualifying event for PFO closure. There were no procedure-related deaths or
      strokes. The most commonly used device was the Amplatzer Septal Occluder (82%).
      Median follow-up was 6 years. A 3.9% of patients had documented residual right-to
      left shunting at last echocardiogram. Recurrent stroke and/or TIA were reported
      in 45 patients, (6.3% of patients with follow-up data). Patients who experienced
      recurrent stroke/TIA were older and had a higher rate of diabetes and
      hypertension than those who did not. The presence of residual shunt did not
      correlate with risk of recurrent events. CONCLUSIONS: Device closure of PFO can
      be performed safely with very good long-term resolution of atrial shunting.
      Recurrent neurologic events after PFO closure may reflect additional comorbid
      risk factors unrelated to the potential for paradoxical embolism. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27027874
TI  - Where to Dig for Fossils: Combining Climate-Envelope, Taphonomy and Discovery
      Models.
AB  - Fossils represent invaluable data to reconstruct the past history of life, yet
      fossil-rich sites are often rare and difficult to find. The traditional fossil
      hunting approach focuses on small areas and has not yet taken advantage of
      modelling techniques commonly used in ecology to account for an organism's past
      distributions. We propose a new method to assist finding fossils at continental
      scales based on modelling the past distribution of species, the geological
      suitability of fossil preservation and the likelihood of fossil discovery in the
      field, and apply it to several genera of Australian megafauna that went extinct
      in the Late Quaternary. Our models predicted higher fossil potentials for
      independent sites than for randomly selected locations (mean Kolmogorov-Smirnov
      statistic = 0.66). We demonstrate the utility of accounting for the distribution
      history of fossil taxa when trying to find the most suitable areas to look for
      fossils. For some genera, the probability of finding fossils based on simple
      climate-envelope models was higher than the probability based on models
      incorporating current conditions associated with fossil preservation and
      discovery as predictors. However, combining the outputs from climate-envelope,
      preservation, and discovery models resulted in the most accurate predictions of
      potential fossil sites at a continental scale. We proposed potential areas to
      discover new fossils of Diprotodon, Zygomaturus, Protemnodon, Thylacoleo, and
      Genyornis, and provide guidelines on how to apply our approach to assist fossil
      hunting in other continents and geological settings. 

PMID- 27027875
TI  - Seroprotection to vaccine-preventable diseases among workers at a Victorian
      tertiary hospital.
AB  - OBJECTIVE: To determine seroprotection for the vaccine-preventable diseases
      (VPDs) measles, mumps, rubella, varicella and hepatitis B among new employees
      seen at a Victorian tertiary hospital staff clinic. METHODS: Employees who
      presented to the staff clinic for immunisation assessment between 1 January 2012
      and 31 December 2013 were included. Demographic data, self-reported disease
      history and previous vaccination status were reviewed retrospectively to
      determine impact on serological results. RESULTS: A total of 1,901 new employees
      were included, 83% of whom were at risk of direct contact with blood or body
      substances. Overall, the proportion of workers seropositive to measles was 88%,
      mumps 90%, rubella 78%, varicella 93% and hepatitis B 80%. Staff born before 1966
      were more likely to have positive measles or mumps serology but negative rubella
      or hepatitis B serology (p<0.05 for each). Staff who self-reported measles (99%
      vs. 93%, p=0.03) or varicella infection (98% vs. 92%, p<0.001) were more likely
      to be seropositive, but those reporting previous vaccination to measles, mumps or
      rubella were no more likely to be seropositive. CONCLUSIONS AND IMPLICATIONS:
      This study demonstrated levels of seropositivity of 78-93% for the five VPDs.
      Despite recognised limitations of serological testing, 10-20% of new employees to
      a healthcare institution lacking seroprotection represents a potentially
      unacceptable risk of nosocomial transmission of these VPDs. Our findings support
      ongoing serological testing of new healthcare staff at risk of direct contact
      with blood or body substances.

PMID- 27027876
TI  - IL18 Gene Variants Influence the Susceptibility to Chagas Disease.
AB  - Chagas disease is a parasitic disorder caused by the infection with the
      flagellated protozoan Trypanosoma cruzi. According to the World Health
      Organization, more than six million people are currently infected in endemic
      regions. Genetic factors have been proposed to influence predisposition to
      infection and development of severe clinical phenotypes like chronic Chagas
      cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine
      that has been proposed to be involved in controlling T. cruzi infection. In this
      study, we analyzed the possible role of six IL18 gene variants (rs5744258,
      rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the
      variation within the locus, in the susceptibility to infection by T. cruzi and/or
      CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas
      disease, classified as seronegative (n = 595), seropositive asymptomatic (n =
      175) and CCC (n = 401), were genotyped using TaqMan probes. Significant
      associations with T. cruzi infection were observed when comparing seronegative
      and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P
      = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P =
      0.0162, OR = 1.22). However, dependence analyses suggested that the association
      was mainly driven by the polymorphism rs360719. This variant is located within
      the promoter region of the IL18 gene, and it has been described that it creates a
      binding site for the transcription factor OCT-1 affecting IL-18 expression
      levels. In addition, no evidence of association was observed between any of the
      analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data
      suggest that genetic variation within the promoter region of IL18 is directly
      involved in the susceptibility to infection by T. cruzi, which provides novel
      insight into disease pathophysiology and adds new perspectives to achieve a more
      effective disease control. 

PMID- 27027877
TI  - Enhanced procedural blank control for organic geochemical studies of critical
      sample material.
AB  - Organic contamination of sedimentary rocks can produce artefacts in studies of
      hydrocarbon composition, and this can have significant negative consequences for
      interpretations of the geobiological record. False positives - that is cases of
      non-syngenetic hydrocarbon biomarkers - are common in Precambrian studies, and
      significant challenges persist despite the intensive effort devoted to these
      studies. Efforts to standardize the 'burden of proof' for distinguishing between
      contamination and syngenetic material have to date failed to yield a simple or
      universal protocol, yet the need remains great, as both bitumen-lean rocks and
      bitumen-rich samples can be vulnerable to the accumulation of false-positive
      signals. In an effort to determine the best approach to quality control, we
      tested the capability of different blank materials to collect ambient
      contamination by assessing their capacity to adsorb hydrocarbons during storage
      in plastic bags and found that commonly used Quartz sand does not provide an
      adequate measure of storage- or laboratory-induced contamination. Brick blanks,
      having the advantage that they can parallel rock samples even during the sawing
      process, are characterized by similar poor adsorption properties. Primarily
      steered by mineralogy, organic carbon content and surface area, model-black
      shales can adsorb up to 20 times more contaminants than sand blanks and up to 200
      times more contaminants than organic-free model-carbonates. This observation
      provides an explanation for reports and observations of seemingly systematic
      stratigraphic variation of contaminants, but mostly should raise awareness for
      the evaluation of procedural blanks, in particular of sample-to-blank ratios,
      when studying bitumen-lean rock samples of varying lithologies. Additionally,
      differences between the hydrocarbon profiles in plastic bags and the hydrocarbon
      signatures transferred to blank materials emphasize difficulties in the
      unequivocal detection of contamination sources. Artificial black shale pellets
      can provide enhanced contamination control in biomarker studies - particularly
      for exceptionally vulnerable samples such as Precambrian rocks, meteorites or
      extraterrestrial sample-return material.

PMID- 27027878
TI  - Efficacy and safety of once-daily insulin degludec/insulin aspart compared with
      once-daily insulin glargine in participants with Type 2 diabetes: a randomized,
      treat-to-target study.
AB  - AIMS: To investigate, in a 26-week, open-label, randomized, treat-to-target
      trial, the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once
      daily vs insulin glargine (IGlar) once daily in adults with Type 2 diabetes,
      inadequately controlled on basal insulin. METHODS: Participants were randomized
      (1:1) to IDegAsp once daily or IGlar once daily in combination with existing oral
      antidiabetic drugs. IDegAsp once daily was administered with the main evening
      meal or the largest meal of the day (agreed at baseline); dosing time was
      maintained throughout the trial. Participants titrated their insulin dose weekly
      to a mean pre-breakfast self-measured plasma glucose target [3.9-4.9 mmol/l (70
      89 mg/dl)]. RESULTS: IDegAsp once daily was non-inferior to IGlar once daily in
      reducing HbA1c after 26 weeks [mean estimated treatment difference IDegAsp once
      daily - IGlar once daily: -0.03% (95% CI -0.20, 0.14)]. The evening meal glucose
      increment was significantly lower with IDegAsp once daily vs IGlar once daily
      [estimated treatment difference IDegAsp once daily - IGlar once daily: -1.32
      mmol/l (95% CI -1.93, -0.72); P < 0.05]. The overall confirmed hypoglycaemia rate
      was higher with IDegAsp once daily (estimated rate ratio 1.43; 95% CI 1.07, 1.92;
      P < 0.05). The rate of nocturnal hypoglycaemia did not significantly differ
      between the IDegAsp and IGlar groups [estimated rate ratio 0.80 (95% CI 0.49,
      1.30); not significant]. CONCLUSIONS: In participants with Type 2 diabetes
      inadequately controlled on basal insulin, IDegAsp once daily improved glycaemic
      control and was non-inferior to IGlar once daily. IDegAsp led to higher rates of
      overall hypoglycaemia than IGlar, with no significant difference in rates of
      nocturnal hypoglycaemia.

PMID- 27027879
TI  - Understanding Protein-Protein Interactions: Essential Players in
      (Patho)physiology (Part 1).
AB  - This is the first of a two-part Editorial by the Guest Editors of the ChemBioChem
      and ChemMedChem joint Special Issue on Protein-Protein Interactions. Part 2 can
      be accessed via http://dx.doi.org/10.1002/cmdc.201600158; the complete issue can
      be viewed here: bit.ly/cbcVIppi. 

PMID- 27027880
TI  - New Hydroxyquinoline-Based Derivatives as Potent Modulators of Amyloid-beta
      Aggregations.
AB  - Copper and zinc have been found to contribute to the burden of amyloid-beta
      (Abeta) aggregations in neurodegenerative Alzheimer's disease (AD). Dysregulation
      of these metals leads to the generation of reactive oxygen species (ROS) and
      eventually results in oxidative damage and accumulation of the Abeta peptide,
      which are the key elements of the disease. Aiming to pursue the discovery of new
      modulators for the disease, we here rationally focused on conjugating the core
      hydroxyquinoline of the metal-protein attenuating compound PBT2 and the N
      methylanilide analogous moiety of the Abeta imaging agent to build a new type of
      multi-target modulators of Abeta aggregations. We found that the N,N
      dimethylanilinyl imines 7a, 8a, and the corresponding amines 7b, 8b exerted
      efficient inhibition of Cu(2+) - or Zn(2+) -induced Abeta aggregations and
      significant disassembly of metal-mediated Abeta aggregated fibrils. Further, 7a
      and 7b also exhibited significant ROC scavenging effects compared to PBT2. The
      results suggested that 7a and 7b are promising lead compounds for the development
      of a new therapy for AD. 

PMID- 27027881
TI  - Time Gating of Chloroplast Autofluorescence Allows Clearer Fluorescence Imaging
      In Planta.
AB  - Chloroplast, an organelle facilitating photosynthesis, exhibits strong
      autofluorescence, which is an undesired background signal that restricts imaging
      experiments with exogenous fluorophore in plants. In this study, the
      autofluorescence was characterized in planta under confocal laser microscopy, and
      it was found that the time-gated imaging technique completely eliminates the
      autofluorescence. As a demonstration of the technique, a clearer signal of
      fluorescent protein-tagged phototropin, a blue-light photoreceptor localized at
      the chloroplast periphery, was visualized in planta. 

PMID- 27027882
TI  - Joint longitudinal hurdle and time-to-event models: an application related to
      viral load and duration of the first treatment regimen in patients with HIV
      initiating therapy.
AB  - Shared parameter joint models provide a framework under which a longitudinal
      response and a time to event can be modelled simultaneously. A common assumption
      in shared parameter joint models has been to assume that the longitudinal
      response is normally distributed. In this paper, we instead propose a joint model
      that incorporates a two-part 'hurdle' model for the longitudinal response,
      motivated in part by longitudinal response data that is subject to a detection
      limit. The first part of the hurdle model estimates the probability that the
      longitudinal response is observed above the detection limit, whilst the second
      part of the hurdle model estimates the mean of the response conditional on having
      exceeded the detection limit. The time-to-event outcome is modelled using a
      parametric proportional hazards model, assuming a Weibull baseline hazard. We
      propose a novel association structure whereby the current hazard of the event is
      assumed to be associated with the current combined (expected) outcome from the
      two parts of the hurdle model. We estimate our joint model under a Bayesian
      framework and provide code for fitting the model using the Bayesian software
      Stan. We use our model to estimate the association between HIV RNA viral load,
      which is subject to a lower detection limit, and the hazard of stopping or
      modifying treatment in patients with HIV initiating antiretroviral therapy.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27027883
TI  - Dementia and caregiver stress.

PMID- 27027884
TI  - The Relationship Between Early Life Events, Parental Attachment, and Psychopathic
      Tendencies in Adolescent Detainees.
AB  - Despite increasing interest in understanding psychopathic traits in youth, the
      role of early environmental factors in the development of psychopathic traits is
      not well understood. No prior studies have directly examined the relationship
      between early life events and psychopathic traits. We examined links between life
      events in the first 4 years of life and indices of the core affective and
      interpersonal components of psychopathy. Additionally, we examined relationships
      between early life events, psychopathic traits, and attachment to parents among
      206 adjudicated adolescents. Results indicated that the total number of early
      life events was positively correlated with indices of the affective component of
      psychopathy. Moreover, psychopathic traits moderated the relationship between the
      number of early life events and later reports of attachment to parents. Findings
      suggest that early environmental factors could have important implications for
      the development of psychopathic traits and may impact attachment to parents for
      youth with psychopathic traits.

PMID- 27027885
TI  - Photospintronics: Magnetic Field-Controlled Photoemission and Light-Controlled
      Spin Transport in Hybrid Chiral Oligopeptide-Nanoparticle Structures.
AB  - The combination of photonics and spintronics opens new ways to transfer and
      process information. It is shown here that in systems in which organic molecules
      and semiconductor nanoparticles are combined, matching these technologies results
      in interesting new phenomena. We report on light induced and spin-dependent
      charge transfer process through helical oligopeptide-CdSe nanoparticles' (NPs)
      architectures deposited on ferromagnetic substrates with small coercive force
      (~100-200 Oe). The spin control is achieved by the application of the chirality
      induced spin-dependent electron transfer effect and is probed by two different
      methods: spin-controlled electrochemichemistry and photoluminescence (PL) at room
      temperature. The injected spin could be controlled by excitation of the
      nanoparticles. By switching the direction of the magnetic field of the substrate,
      the PL intensity could be alternated. 

PMID- 27027886
TI  - Analysis of bipolar maintenance treatment with lithium versus olanzapine
      utilizing Multi-state Outcome Analysis of Treatments (MOAT).
AB  - OBJECTIVES: Survival analysis has superseded most other analytic techniques for
      maintenance treatment studies over recent decades, despite providing results
      based solely on a single time-point predefined event. The aim of the present
      study was to develop the Multi-state Outcome Analysis of Treatments (MOAT), to
      provide more pragmatic information for clinicians and investigators in guiding
      maintenance treatment decisions. The present study was one of two published
      studies on the development of MOAT procedures, involving a one-year comparison of
      olanzapine versus lithium in recently manic patients. METHODS: MOAT partitions
      total survival time into clinically distinct periods that are operationally
      defined by cut points on established rating scales. For bipolar disorders, the
      clinical states are remission, subsyndromal and syndromal mania, mixed states,
      and subsyndromal and syndromal depression. RESULTS: MOAT re-analyses of the
      clinical trial revealed clinically important findings not identified when
      utilizing Kaplan-Meier survival analyses. Compared to patients treated with
      lithium, patients taking olanzapine experienced significantly more time in
      subsyndromal depression. Patients taking lithium spent significantly more time in
      mixed states than did patients taking olanzapine. CONCLUSIONS: MOAT provided
      detailed information on treatment outcomes that was not provided by Kaplan-Meier
      survival analysis. Its capability to identify and aggregate time in different
      clinical states of bipolar disorder may aid in identifying drug effects that are
      important in selecting and conducting maintenance treatment.

PMID- 27027887
TI  - Effects of successive relearning on recall: Does relearning override the effects
      of initial learning criterion?
AB  - Retrieval practice improves memory for many kinds of materials, and numerous
      factors moderate the benefits of retrieval practice, including the amount of
      successful retrieval practice (referred to as the learning criterion). In
      general, the benefits of retrieval practice are greater with more than with less
      successful retrieval practice; however, learning items to a higher (vs. lower)
      criterion requires more time and effort. If students plan on relearning material
      in a subsequent study session, does the benefit of learning to a higher criterion
      during an initial session persist? In Session 1, participants studied and
      successfully recalled Swahili-English word pairs one, two, three, four, five,
      six, or seven times. In subsequent sessions, all of the pairs were relearned to a
      criterion of one correct recall at one-week intervals across four or five
      successive relearning sessions. Experiments 1 and 2 revealed that the substantial
      benefits of learning to a higher initial criterion during the first session do
      not persist across relearning sessions. This relearning-override effect was also
      demonstrated in Experiment 2 after a one-month retention interval. The
      implications of relearning-override effects are important for theory and for
      education. For theories of test-enhanced learning, they support the predictions
      of one theory and appear inconsistent with the predictions of another. For
      education, if relearning is to occur, using extra time to learn to a higher
      initial learning criterion is not efficient. Instead, students should devote
      their time to subsequent spaced relearning sessions, which produce substantial
      gains in recall performance.

PMID- 27027888
TI  - Decision making in MS: factors affecting engagement in treatment choices.

PMID- 27027890
TI  - Disability may influence patient willingness to participate in decision making on
      first-line therapy in multiple sclerosis.
AB  - Patient autonomy is a concept that implies variable degrees of patient
      participation in different aspects of health and healthcare, including the choice
      of therapy. This study, conducted in patients with multiple sclerosis (MS),
      examined several factors in relation to the patient's role in the therapeutic
      decision-making process. One hundred newly diagnosed patients with MS attending
      their first ever specialist consultation at the MS center of Catania, Italy, were
      consecutively enrolled in a single-center, open, observational study. Clinical
      and demographic data were collected as part of this routine first consultation.
      Through administration of the Control Preferences Scale, we ascertained the
      patients' willingness to participate in the decision-making process on their
      first-line treatment, classifying them, on the basis of their attitude, as
      passive, collaborative or active. Of 100 patients with MS, 40 had a passive
      attitude, while 35 were willing to collaborate and 25 wanted to play an active
      role in the decision-making process. The patients showing an active attitude had
      a significantly higher Expanded Disability Status Scale score and a significantly
      higher number of relapses (p<0.5 for both) than those who showed other attitudes.
      Persons with MS prefer to know the benefits and risks related to the first-line
      treatment. Those with higher disability prefer to be active in the decision
      making process. 

PMID- 27027889
TI  - Amyotrophic lateral sclerosis and environmental factors.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that
      affects central and peripheral motor neuron cells. Its etiology is unknown,
      although a relationship between genetic background and environmental factors may
      play a major role in triggering the neurodegeneration. In this review, we analyze
      the role of environmental factors in ALS: heavy metals, electromagnetic fields
      and electric shocks, pesticides, beta-N-methylamino-L-alanine, physical activity
      and the controversial role of sports. The literature on the single issues is
      analyzed in an attempt to clarify, as clearly as possible, whether each risk
      factor significantly contributes to the disease pathogenesis. After summarizing
      conflicting observations and data, the authors provide a final synthetic
      statement. 

PMID- 27027891
TI  - Effects of treadmill training on cognitive and motor features of patients with
      mild to moderate Parkinson's disease: a pilot, single-blind, randomized
      controlled trial.
AB  - The aim of this pilot randomized controlled trial was to evaluate the effects of
      treadmill training on cognitive and motor performance in patients with
      Parkinson's disease (PD). Seventeen persons with mild to moderate PD were
      enrolled. Nine patients were allocated to the Intervention group and received
      twelve 45-minute sessions of treadmill training: one session a day, three days a
      week, for four consecutive weeks. Eight patients were allocated to the Control
      group; these patients did not undergo physical training but were required to have
      regular social interactions, following a specific lifestyle program. All the
      patients were evaluated at baseline and one month later. The primary outcome
      measures were the Frontal Assessment Battery-Italian version (FAB-it) and the 6
      minute walking test (6MWT). At the one month evaluation significant differences
      were found between the groups in their performance on the FAB-it (p=0.005) and
      the 6MWT (p=0.018). Our findings support the hypothesis that treadmill training
      might effectively improve cognitive and motor features in patients with PD.

PMID- 27027892
TI  - Melatonin 4 mg as prophylactic therapy for primary headaches: a pilot study.
AB  - There is growing evidence that headaches are connected to melatonin secretion.
      Our aim was to assess the potential effectiveness of melatonin for primary
      headache prevention. Forty-nine patients (37 with migraine and 12 with chronic
      tension-type headache, TTH) were prescribed oral melatonin, 4 mg, 30 minutes
      before bedtime for six months. Forty-one (83.6%) of the 49 patients completed the
      study, while eight dropped out for personal reasons. A statistically significant
      reduction in headache frequency was found between baseline and final follow-up
      after six months of treatment (p=0.033 for TTH patients and p<0.001 for
      migraineurs). The Headache Impact Test score was significantly reduced in both
      groups of headache patients (p=0.002 and p<0.001, respectively). At baseline,
      melatonin levels, measured both during a headache attack and a pain-free period,
      did not differ between patients with TTH and migraineurs (p=0.539 and p=0.693,
      respectively), and no statistically significant differences in Hamilton
      Depression Rating Scale scores were found between the two groups. This pilot
      study shows promising results, in terms of headache frequency reduction and daily
      quality of life improvement, in both groups.

PMID- 27027893
TI  - Global fractional anisotropy and mean diffusivity together with segmented brain
      volumes assemble a predictive discriminant model for young and elderly healthy
      brains: a pilot study at 3T.
AB  - Several parameters of brain integrity can be derived from diffusion tensor
      imaging. These include fractional anisotropy (FA) and mean diffusivity (MD).
      Combination of these variables using multivariate analysis might result in a
      predictive model able to detect the structural changes of human brain aging. Our
      aim was to discriminate between young and older healthy brains by combining
      structural and volumetric variables from brain MRI: FA, MD, and white matter
      (WM), gray matter (GM) and cerebrospinal fluid (CSF) volumes. This was a cross
      sectional study in 21 young (mean age, 25.71+/-3.04 years; range, 21-34 years)
      and 10 elderly (mean age, 70.20+/-4.02 years; range, 66-80 years) healthy
      volunteers. Multivariate discriminant analysis, with age as the dependent
      variable and WM, GM and CSF volumes, global FA and MD, and gender as the
      independent variables, was used to assemble a predictive model. The resulting
      model was able to differentiate between young and older brains: Wilks' lambda =
      0.235, chi2 (6) = 37.603, p = .000001. Only global FA, WM volume and CSF volume
      significantly discriminated between groups. The total accuracy was 93.5%; the
      sensitivity, specificity and positive and negative predictive values were 91.30%,
      100%, 100% and 80%, respectively. Global FA, WM volume and CSF volume are
      parameters that, when combined, reliably discriminate between young and older
      brains. A decrease in FA is the strongest predictor of membership of the older
      brain group, followed by an increase in WM and CSF volumes. Brain assessment
      using a predictive model might allow the follow-up of selected cases that deviate
      from normal aging.

PMID- 27027894
TI  - Does chronic exposure to mobile phones affect cognition?
AB  - Mobile phones form an integral part of our modern lifestyle. Following the
      drastic rise in mobile phone use in recent years, it has become important to
      study its potential public health impact. Amongst the various mobile phone health
      hazards, the most alarming is the possible effect on the brain. The aim of the
      present study was to explore whether chronic exposure to mobile phones affects
      cognition. Ninety subjects aged 17-25 years with normal hearing were recruited
      for the study and divided into three groups according to their duration of mobile
      phone use. No significant differences in N100, P200, N200, P300 latencies or N2
      P300 amplitude were observed. Our results suggest that chronic mobile phone
      exposure does not have detrimental effects on cognition. 

PMID- 27027895
TI  - Andrographis Paniculata shows anti-nociceptive effects in an animal model of
      sensory hypersensitivity associated with migraine.
AB  - Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition
      and neuronal activation of central structures involved in migraine pain. In order
      to identify therapeutic strategies for migraine pain, we evaluated the anti
      nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the
      hyperalgesia induced by NTG administration in the formalin test. We also analyzed
      mRNA expression of cytokines in specific brain areas after AP treatment. Male
      Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or
      vehicle injection. The data show that AP extract significantly reduced NTG
      induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In
      addition, AP extract reduced IL-6 mRNA expression in the medulla and
      mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These
      findings suggest that AP extract may be a potential therapeutic approach in the
      treatment of general pain, and possibly of migraine.

PMID- 27027897
TI  - Non-linear resistance training reduces inflammatory biomarkers in persons living
      with HIV: A randomized controlled trial.
AB  - The purpose of this study is to analyse the effect of 12 weeks of non-linear
      resistance training (NLRT) on anthropometry, muscle strength and inflammatory
      biomarkers in persons infected with human immunodeficiency virus (PIHIV). Thirty
      previously sedentary PIHIVs were randomized into the NLRT (n = 15) and control
      (CON, n = 15) groups. NLRT group were submitted to 12 weeks of training, whereas
      the CON group maintained their daily habits. At baseline and after 12 weeks, both
      groups underwent anthropometric evaluations and blood sampling for the analysis
      of inflammatory biomarkers. Analysis of covariance using preintervention values
      as covariate was performed to determine the effects of exercise on anthropometry,
      muscle strength, cytokines levels and T cells. Significance was set at p < 0.05.
      After 12 weeks of intervention, there was a decrease in subcutaneous body fat (p
      < .0001), neck, abdomen and waist circumferences (p < .05), waist-to-hip ratio (p
      = .009), blood levels of interleukin (IL)-1beta (p = .029), IL-6 (p = .005), IL-8
      (p = .010), and tumour necrosis factor (TNF)-alpha (p = .001) and an increase in
      muscle strength (p < .0001), IL-10 levels (p = .030) and CD4(+) (p = .004) and
      CD8(+) (p < .0001) counts in the NLRT compared to CON group. Twelve weeks of NLRT
      promoted positive changes in the body fat, body circumferences, muscular strength
      and inflammatory profile in PIHIV. 

PMID- 27027898
TI  - Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell
      Carcinoma.
AB  - PURPOSE: Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in
      transforming from pyruvate into lactate, has been reported to be overexpressed in
      various advanced cancer and its silencing has turned out to be tumor suppressive.
      Previous studies have showed that the expression of LDHA was higher in renal cell
      carcinoma (RCC) than that in corresponding normal renal tissue. However, the
      function of LDHA in RCC, and its possible mechanism in tumor progression, has not
      been investigated. METHODS: MTT and cell cycle assay were performed to explore
      the growth of the renal cells. Transwell assay for the migration and invasion and
      tube formation were conducted to detect the metastatic properties of the renal
      cancer. RESULTS: Here, we show that siRNA-mediated knockdown of LDHA inhibits
      cell proliferation by decreasing cell cycle and promoting apoptosis in renal
      cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression
      of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2
      and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory
      and invasive ability by reducing the expression of matrix metalloproteinase (MMP)
      2 and MMP-9. CONCLUSIONS: These findings are consistent with the view that LDHA,
      as an oncogene, might be a potential therapeutic target in RCC.

PMID- 27027899
TI  - Left Atrial Geometry Improves Risk Prediction of Thromboembolic Events in
      Patients With Atrial Fibrillation.
AB  - BACKGROUND: Left atrial (LA) sphericity (LASP) is a new remodeling parameter
      based on LA shape analysis, with independent predictive value for recurrence
      after atrial fibrillation (AF) ablation. OBJECTIVES: To evaluate the association
      between LASP and thromboembolic events (TE) in patients with AF. METHODS: Twenty
      nine AF patients and prior TE and 29 age- and gender-matched controls were
      included. LASP was calculated using a 3D-LA reconstruction. The LA appendage
      (LAA) volume and morphology were assessed. ROC curve analysis was performed for
      LASP, LA volume, LAA volume, and CHAD/CHA2 D-VASc scores (Stroke2 -the grouping
      variable-was excluded). RESULTS: Mean age of the study population was 61 +/- 11
      years (79.3% males, 53.4% hypertension, 8.6% diabetes). Patients with prior TE
      had higher LASP than those without (82.5 +/- 3.3% vs. 80.2 +/- 3.1%, P = 0.008);
      there were no differences in CHAD or CHA2 D-VASc scores, LA volume, LAA volume,
      or LAA morphology. The C-statistic was higher for LASP (0.71) than for other
      tested variables (CHAD score = 0.58, CHA2 D-VASc score = 0.59, LA volume = 0.50,
      LAA volume = 0.46; P < 0.01 for all vs. LASP). The best cutoff value for LASP was
      83.6% (sensitivity 0.52, specificity 0.90). Logistic regression analysis showed
      predictive value for LASP (OR 1.26 per each 1% increase [1.85-52.20], P = 0.013),
      but not for clinical risk scores. The addition of LASP to the CHAD and CHA2 D
      VASc scores increased the predictive value over the risk scores alone (P =
      0.004), and reclassified 45.5% of patients with CHAD = 0 (no anticoagulation
      indicated) to moderate-risk (anticoagulation indicated). CONCLUSION: LA
      sphericity is associated with prior TE in AF patients and improves the
      performance of the CHAD and CHA2 D-VASc scores alone.

PMID- 27027900
TI  - GBA Mutations Are Associated With Earlier Onset and Male Sex in Dementia With
      Lewy Bodies.
AB  - BACKGROUND: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy
      body diseases characterized by similar pathological features. Several studies
      have shown a relation between alterations in the glucocerebrosidase gene (GBA)
      and the development of LB diseases. Here, we explored the role of GBA mutations
      in Spanish DLB patients. METHODS: GBA mRNA sequences were analyzed in a
      neuropathological (50 DLB, 43 PD, and 34 control brains) and in a clinical cohort
      (47 DLB patients and 131 unaffected individuals). RESULTS: Sixteen GBA mutation
      carriers were identified, 5 of which were brains with pure DLB. The most common
      mutation, E326K, was strongly associated with pure DLB and PD with dementia. GBA
      mutations were overrepresented in men and associated with earlier DLB onset.
      CONCLUSIONS: GBA mutations are also an important risk factor for DLB development
      in the Spanish population, are associated with earlier disease onset, and are
      more prevalent in men. (c) 2015 International Parkinson and Movement Disorder
      Society.

PMID- 27027901
TI  - Factors Associated with Supplemental Formula Feeding of Breastfeeding Infants
      During Postpartum Hospital Stay.
AB  - OBJECTIVE: To determine reasons potentially amenable to interventions that
      mothers choose to supplement breastfeeding with formula in the immediate
      postpartum period. STUDY DESIGN: We distributed surveys to all mothers in the
      postpartum unit who delivered a live newborn on day of maternal discharge to
      assess feeding behaviors during their inpatient admission. We evaluated, when
      applicable, their reasons for supplementation and examined cultural and
      demographic information to uncover trends for formula use and potential areas for
      provider intervention. RESULTS: Seven hundred twelve of 1,400 mothers responded,
      of which 478 (65%) reported supplementing breastfeeding with formula (BF+F). The
      most common reasons for formula supplementation were perception of inadequate
      milk supply (36.4%), desire for sleep (35.4%), and a plan to breast and bottle
      feed (35.2%). Exclusive breastfeeding (EBF) was associated with primiparous
      status (OR 1.95; 95% CI 1.3-3.0), higher education level (OR 2.6; 95% CI 1.7
      3.9), and having been breastfed as an infant (OR 1.54; 95% CI 1-2.37). Mothers
      who experienced skin-to-skin contact also had higher rates of EBF (29.5% versus
      19.9%). Factors associated with exclusive formula feeding included single marital
      status, birth of mother in the United States, Catholic religion, multiparity, and
      cesarean delivery. Religious and cultural factors also played important roles in
      maternal feeding behaviors. CONCLUSION: Clinicians can anticipate risk factors
      for formula use in mothers who plan to breastfeed and tailor counseling
      appropriately to increase EBF rates.

PMID- 27027902
TI  - Extension of N-Heteroacenes through a Four-Membered Ring.
AB  - The synthesis of novel pi-extended N-heteroacenes, which have a large
      tetraazaacene subunit and a quinoxaline subunit connected through a four-membered
      ring, is reported. They were studied with experimental and computational methods
      in comparison to the corresponding tetraazaacenes. As found from the DFT
      calculation, the four-membered ring is a better linker than a five-membered ring
      or a C-C single bond to extend N-heteroacenes for a new design of n-type
      semiconductors in terms of the spatial delocalization and energy level of LUMO as
      well as the reorganization energy. In solution-processed thin film transistors,
      the pi-extended N-heteroacenes are found to function as n-type semiconductors
      with field effect mobility of up to 0.02 cm(2)  V(-1)  s(-1) under ambient
      conditions. 

PMID- 27027903
TI  - NASPGHAN Clinical Report: Surveillance, Diagnosis, and Prevention of Infectious
      Diseases in Pediatric Patients With Inflammatory Bowel Disease Receiving Tumor
      Necrosis Factor-alpha Inhibitors.
AB  - Children and adolescents with inflammatory bowel disease (IBD) receiving therapy
      with tumor necrosis factor alpha inhibitors (anti-TNFalpha) pose a unique
      challenge to health care providers in regard to the associated risk of infection.
      Published experience in adult populations with distinct autoinflammatory and
      autoimmune diseases treated with anti-TNFalpha therapies demonstrates an
      increased risk of serious infections with intracellular bacteria, mycobacteria,
      fungi, and some viruses; however, there is a paucity of robust pediatric data.
      With a rising incidence of pediatric IBD and increasing use of biologic
      therapies, heightened knowledge and awareness of infections in this population is
      important for primary care pediatricians, pediatric gastroenterologists, and
      infectious disease (ID) physicians. This clinical report is the result of a
      consensus review performed by pediatric ID and gastroenterology physicians
      detailing relevant published literature regarding infections in pediatric
      patients with IBD receiving anti-TNFalpha therapies. The objective of this
      document is to provide comprehensive information for prevention, surveillance,
      and diagnosis of infections based on current knowledge, until additional
      pediatric data are available to inform evidence-based recommendations.

PMID- 27027904
TI  - Transitions in Pediatric Gastroenterology: Results of a National Provider Survey.
AB  - OBJECTIVES: Transition and transfer to adult-oriented health care is an important
      yet challenging task for adolescents and young adults with chronic medical
      conditions. Transition practices vary widely, but a paucity of data makes
      determination of best practices difficult. We described North American pediatric
      gastroenterologists' preferences and present transition practice patterns and
      explored whether experience affected providers' perspectives. METHODS: An online
      survey was distributed via e-mail to members of the North American Society of
      Pediatric Gastroenterology, Hepatology and Nutrition. Participation was voluntary
      and answers were anonymous. Quantitative and qualitative analysis was performed.
      RESULTS: Almost three quarters of the 175 respondents describe providing
      transition or self-care management education, but only 23% use structured
      readiness assessments. Most respondents (88%) report having age cutoffs above
      which they no longer accept new referrals, with the most common age being 18
      years (57%). One third report the ability to provide age-appropriate care to
      patients older than 21 years. Only 6% indicate that their practice or institution
      should provide care for individuals older than 25 years. Many (63%) indicate that
      their practice or institution has a policy regarding age of transfer, but most
      (79%) are flexible. Provider preferences for triggers to transfer to adult care
      diverge widely between age, milestones, and comorbidities. Overall, parent (81%)
      and patient (74%) attachment to pediatric health care providers are cited as the
      most common barriers to transition. CONCLUSIONS: Preferences and practices
      surrounding transition preparation and transfer to adult care vary widely,
      reflecting continued uncertainty regarding optimal transition strategies.

PMID- 27027905
TI  - Health-Related Quality of Life and Parental Stress in Children With Fecal
      Incontinence: A Normative Comparison.
AB  - OBJECTIVE: The aim of the present study was to describe the quality of life and
      parenting stress associated with a child with fecal incontinence (FI). METHODS:
      Female caregivers (n = 170) of children of 3 to 12 years age with FI completed a
      broad and general measure of quality of life and a measure of parenting stress.
      Results were compared with proxy reports for a normative sample of healthy
      children. RESULTS: Caregivers of children with FI reported significantly impaired
      quality of life for their children and increased parenting stress in all of the
      respective domains relative to healthy controls. Impairments reported by
      caregivers were large in magnitude. Similarly, rates of parenting stress were at
      or greater than the 98th percentile for caregivers of children with FI.
      CONCLUSIONS: Children with fecal incontinence and their families are in need of
      interventions targeting their quality of life and the stress associated with
      caregiving. FI appears to be particularly stressful for caregivers who may be in
      need of support beyond medical management of their child's bowel. Moreover,
      additional refinements in disease-specific quality of life assessment are needed
      in this population. Such refinement would allow for more precise measurement of
      the quality of life processes that are unique to FI.

PMID- 27027906
TI  - Doxorubicin-Induced Gut Toxicity in Piglets Fed Bovine Milk and Colostrum.
AB  - OBJECTIVE: Chemotherapy-induced intestinal toxicity is a common adverse effect of
      cancer treatment. We hypothesized that a milk diet containing bovine colostrum
      (BC) would reduce intestinal toxicity in doxorubicin-treated piglets. METHODS:
      "Study 1" investigated intestinal parameters 9 days after a single dose of
      doxorubicin (1 * 75 mg/m) in piglets fed bovine milk enriched with whey protein
      (BM). In "study 2," responses to doxorubicin treatment were investigated in
      piglets receiving either 7 BC feedings per day (Only-BC, n = 13), 4 BC feedings
      (High-BC, n = 13), 2 BC feedings (Low-BC, n = 14), or no BC (only BM, n = 13).
      RESULTS: Doxorubicin treatment induced clinical signs of intestinal toxicity with
      diarrhea and weight loss, relative to controls (P < 0.05). White blood cells,
      hexose absorptive function, plasma citrulline, weights of intestine, colon, and
      spleen were reduced, whereas gut permeability and plasma C-reactive protein
      levels were increased (all P < 0.05). Limited or no effects were observed for
      digestive enzymes, proinflammatory cytokines, or tight-junction proteins in the
      intestine. Increasing BC supplementation to doxorubicin-treated piglets (study 2)
      had no consistent effects on plasma C-reactive protein and citrulline levels,
      intestinal morphology, digestive enzymes, permeability, or proinflammatory
      cytokines. Only-BC pigs, however, had lower diarrhea severity toward the end of
      the experiment (P < 0.05 vs BM) and across the BC groups, intestinal toxicity was
      reduced (P < 0.01). CONCLUSIONS: Doxorubicin-treated piglets are relevant for
      studying chemotherapy-induced gut toxicity. Colostrum supplementation had limited
      effects on doxorubicin-induced toxicity in milk-fed piglets suggesting that
      colostrum and a bovine milk diet enriched with whey protein provided similar
      protection of the developing intestine from chemotherapy-induced toxicity.

PMID- 27027907
TI  - The future of pelvic floor services in the UK.
AB  - AIM: The study aimed to determine the current state of UK pelvic floor services
      and to discuss future strategies. METHOD: A questionnaire developed by the Pelvic
      Floor Society was sent in 2014 to the 175 colorectal units recognized by the
      Association of Coloproctology of Great Britain and Ireland. Questions included
      type of centre, frequency of pelvic floor clinics/interdisciplinary joint pelvic
      floor clinics/multidisciplinary meetings (MDMs) and workload. RESULTS: Sixty
      seven (38%) centres replied including 75% of units with a consultant who was as
      member of the Pelvic Floor Society. Of the 67 centres 39% were tertiary centres
      for pelvic floor surgery (tertiary), 48% performed some pelvic floor surgery
      (regional) and 13% did not perform any (local). Ninety-six per cent of tertiary
      referral centres served a population over 500 000. The mean number of whole time
      equivalent consultants in tertiary centres was 1.03 and 0.77 in regional centres.
      Eighty per cent of tertiary centres and 56% of regional centres ran pelvic floor
      clinics. Eighty-four per cent of tertiary referral and 75% of regional units held
      or attended an MDM. Anal ultrasonography, anorectal physiology and proctography
      were performed in 96% of tertiary centres compared with 50% of non-tertiary
      units. CONCLUSION: The provision of pelvic floor services includes local,
      regional and tertiary centres. The overall response rate was low (38%) and biased
      to centres with a consultant who was a member of the Pelvic Floor Society. Not
      all regional or tertiary centres held an MDM or a pelvic floor clinic. Given the
      nature of pelvic floor pathology an integrated service should be aimed at linking
      different centres and specialities.

PMID- 27027908
TI  - A case study of topographical disorientation: behavioural intervention for
      achieving independent navigation.
AB  - This study introduces an intervention that enabled a man (LH) with acquired
      topographical disorientation (TD) to travel independently without fear of getting
      lost. Adapting an errorless method, LH learned to use a smartphone to find his
      routes accurately and reliably. A time-series design (A1-B1-A2-B2) was used: In
      all phases, LH was given a printed map on which city locations were indicated. He
      had to walk to the indicated locations while naturalistic outcomes were recorded.
      In Phases A, he navigated without his smartphone, and in Phases B, with it. In
      Phases A, LH made numerous surplus direction changes, and openly expressed his
      frustration. In Phases B, he did not have surplus direction changes and could
      calmly find his routes. Before intervention, LH and his wife were frustrated and
      worried about his way-finding. They rated their confidence in his navigational
      ability and his actual ability in way-finding to various locations as low. After
      intervention, they were more confident that LH could travel by himself without
      getting lost and rated his ability as much higher for various scenarios. As a
      consequence of intervention LH gained greater independence and quality of life.

PMID- 27027909
TI  - Gut microbes in correlation with mood: case study in a closed experimental human
      life support system.
AB  - BACKGROUND: Gut microbial community, which may influence our mood, can be shaped
      by modulating the gut ecosystem through dietary strategies. Understanding the gut
      brain correlationship in healthy people is important for maintenance of mental
      health and prevention of mental illnesses. METHODS: A case study on the
      correlation between gut microbial alternation and mood swing of healthy adults
      was conducted in a closed human life support system during a 105-day experiment.
      Gut microbial community structures were analyzed using high-throughput sequencing
      every 2 weeks. A profile of mood states questionnaire was used to record the mood
      swings. Correlation between gut microbes and mood were identified with partial
      least squares discrimination analysis. KEY RESULTS: Microbial community
      structures in the three healthy adults were strongly correlated with mood states.
      Bacterial genera Roseburia, Phascolarctobacterium, Lachnospira, and Prevotella
      had potential positive correlation with positive mood, while genera
      Faecalibacterium, Bifidobacterium, Bacteroides, Parabacteroides, and Anaerostipes
      were correlated with negative mood. Among which, Faecalibacterium spp. had the
      highest abundance, and showed a significant negative correlation with mood.
      CONCLUSIONS & INFERENCES: Our results indicated that the composition of microbial
      community could play a role in emotional change in mentally physically healthy
      adults.

PMID- 27027910
TI  - Leptin and Adiponectin Serum Levels from Infancy to School Age: Factors
      Influencing Tracking.
AB  - BACKGROUND: Early adiponectin and leptin in children correlate with those
      measured at a later age. Prenatal and early life factors may influence the
      pattern of leptin and adiponectin longitudinal changes. We aimed to identify
      subgroups of children with distinct trajectories of leptin and adiponectin over
      the first eight years of life, and to explore determinants predisposing an
      individual to be included in a specific trajectory class. METHODS: The analysis
      was based on data obtained from the EU Childhood Obesity Project (CHOP) cohort.
      The current study involved 459 children with adiponectin and leptin measured at 6
      months, 51/2 and 8 years of age. RESULTS: Three groups of leptin trajectories
      were identified: low-decreasing, medium-stable, and high-increasing, and two
      trajectory groups for adiponectin: lower and higher. The risk to be classified in
      the high-increasing group was higher than in the low-decreasing group for female
      gender (OR 10.67; 95% CI 4.94-23.05; p < 0.001); formula feeding (OR 3.34; 95% CI
      1.11-10.09; p < 0.05); maternal overweight (OR 4.43; 95% CI 2.20-8.94; p <
      0.001); and smoking in pregnancy (OR 4.14; 95% CI 2.07-8.29; p < 0.001). No
      predictors for being in the higher vs. lower adiponectin group were discovered.
      CONCLUSIONS: Mothers' smoking during pregnancy, maternal overweight, and formula
      feeding distinguished different courses of leptin trajectories; but the effect
      may be associated with changes in adiposity.

PMID- 27027911
TI  - Interaction between the moss Physcomitrella patens and Phytophthora: a novel
      pathosystem for live-cell imaging of subcellular defence.
AB  - Live-cell imaging of plant-pathogen interactions is often hampered by the tissue
      complexity and multicell layered nature of the host. Here, we established a novel
      pathosystem with the moss Physcomitrella patens as host for Phytophthora. The tip
      growing protonema cells of this moss are ideal for visualizing interactions with
      the pathogen over time using high-resolution microscopy. We tested four
      Phytophthora species for their ability to infect P. patens and showed that P.
      sojae and P. palmivora were only rarely capable to infect P. patens. In contrast,
      P. infestans and P. capsici frequently and successfully penetrated moss
      protonemal cells, showed intracellular hyphal growth and formed sporangia. Next
      to these successful invasions, many penetration attempts failed. Here the
      pathogen was blocked by a barrier of cell wall material deposited in papilla-like
      structures, a defence response that is common in higher plants. Another common
      response is the upregulation of defence-related genes upon infection and also in
      moss we observed this upregulation in tissues infected with Phytophthora. For
      more advanced analyses of the novel pathosystem we developed a special set-up
      that allowed live-cell imaging of subcellular defence processes by high
      resolution microscopy. With this set-up, we revealed that Phytophthora infection
      of moss induces repositioning of the nucleus, accumulation of cytoplasm and
      rearrangement of the actin cytoskeleton, but not of microtubules.

PMID- 27027912
TI  - Influence of some plant extracts on the transdermal absorption and penetration of
      marker penetrants.
AB  - CONTEXT: Plant extracts are commonly used in a number of cosmetics and topical
      pharmaceuticals. The effects on such extracts on the subsequent dermal absorption
      and penetration of other cosmetic ingredients needs to be evaluated. OBJECTIVE:
      This study demonstrates the effect of some natural extracts routinely found in
      cosmetics on the dermal absorption and penetration of marker penetrants. METHODS:
      Aqueous ethanolic extracts of Gingko biloba, Lavendula angustifolia, Rosmarinus
      officinale, Mentha piperita, Matricaria recutita, Persea Americana, Avena sativa,
      Zingiber officinale were prepared. 14C-caffeine and 14C-salicylic acid were
      topically dosed with either 10% solutions of natural extracts or ethanol
      (control) using a flow through in vitro porcine skin diffusion system. Samples
      were analyzed with liquid scintillation counter. The parameters of flux,
      permeability, and percent dose absorbed/retained were calculated and compared.
      RESULTS: The dermal absorption of 14C-caffeine was significantly higher (p >=
      0.05) with avocado, chamomile, ginger and peppermint extract as compared to the
      control ethanol; while dermal absorption of 14C-salicylic acid was significantly
      greater with ginkgo and chamomile extract as compared to ethanol. Over four fold
      increase in flux and permeability of caffeine with avocado extract was observed
      while chamomile and peppermint extracts increased the flux and permeability of
      caffeine over three fold. Gingko and chamomile extracts increased salicylic
      acid's flux and permeability by two fold. Sum of %dose skin residue + %absorption
      in receptor fluid for different extracts exhibited the similar trend as shown by
      flux and permeability. The other natural extracts tested did not produce
      statistically significant effects on dermal penetration parameters for both
      caffeine and salicylic acid (p >= 0.05). CONCLUSION: These results emphasize the
      influence of natural plant extracts on the transdermal penetration of hydrophilic
      (caffeine) and hydrophobic (salicylic acid) penetrants and thus warrants the
      consideration as to their safety in cosmetics and topical pharmaceuticals
      containing natural extracts.

PMID- 27027913
TI  - Respiratory gating for proton beam scanning versus photon 3D-CRT for breast
      cancer radiotherapy.
AB  - Background Respiratory gating and proton therapy have both been proposed to
      reduce the cardiopulmonary burden in breast cancer radiotherapy. This study aims
      to investigate the additional benefit of proton radiotherapy for breast cancer
      with and without respiratory gating. Material and methods Twenty left-sided
      patients were planned on computed tomography (CT)-datasets acquired during
      enhanced inspiration gating (EIG) and free-breathing (FB), using photon three
      dimensional conformal radiation therapy (3D-CRT) and scanned proton beams. Ten
      patients received treatment to the whole breast only (WBO) and 10 were treated to
      the breast and the regional lymph nodes (BRN). Dosimetric parameters
      characterizing the coverage of target volumes and the cardiopulmonary burden were
      compared using a paired, two-tailed Student's t-test. Results Protons ensured
      comparable or better target coverage than photons in all patients during both EIG
      and FB. The heterogeneity index decreased from 12% with photons to about 5% with
      protons. The mean dose to the ipsilateral lung was reduced in BRN patients from
      12 Gy to 7 Gy  (RBE) in EIG and from 14 Gy to 6-7 Gy (RBE) in FB, while for WBO
      patients all values were about 5-6 Gy (RBE). The mean dose to heart decreased by
      a factor of four in WBO patients [from 1.1 Gy to 0.3 Gy (RBE) in EIG and from 2.1
      Gy to 0.5 Gy (RBE) in FB] and 10 in BRN patients [from 2.1 Gy to 0.2 Gy (RBE) in
      EIG and from 3.4 Gy to 0.3 Gy (RBE) in FB]. Similarly, the mean and the near
      maximum dose to the left anterior descending artery (LAD) were significantly
      lower (p < 0.05) with protons in comparison with photons. Conclusion Proton spot
      scanning has a high potential to reduce the irradiation of organs at risk and
      other normal tissues for most patients, beyond what could be achieved with EIG
      and photon therapy. The largest dose sparing has been seen for BRN patients, both
      in terms of cardiopulmonary burden and integral dose. 

PMID- 27027914
TI  - Genome-wide Significant Associations for Cannabis Dependence Severity: Relevance
      to Psychiatric Disorders.

PMID- 27027915
TI  - Outcomes of Wound Dehiscence Post-Penetrating Keratoplasty.
AB  - PURPOSE: Penetrating keratoplasties (PKs) carry a lifetime risk of developing
      wound dehiscence, which can lead to severe consequences to vision. To better
      understand the risk, we analyzed the characteristics and outcomes of a series of
      patients with wound dehiscence post-PK. METHODS: Data were collected
      retrospectively on 31 eyes from 30 patients with a history of wound dehiscence
      repair post-PK between January 1, 2009, and April 30, 2014, and followed up at
      the Cornea Service at Wills Eye Hospital. Only patients who had surgical repair
      of an open wound dehiscence were included, excluding those with wound slippage
      but no aqueous leak. RESULTS: The mean age at wound dehiscence was 56 years with
      a mean time from PK to dehiscence of 9.8 years. Among the 31 eyes, 26 (26/31,
      84%) had trauma-induced dehiscence, while 5 had unknown causations or no reported
      trauma. The mean size of dehiscence was 153 +/- 66 degrees. Visual outcomes
      ranged from 20/50 to no light perception, with a majority between 20/100 and hand
      motion (18/30, 60%). Twenty eyes (20/26, 76%) lost their lens at dehiscence. All
      10 phakic eyes lost their lenses. Five patients retained their lens implants and
      had a better mean visual outcome (average = 20/400) than the 10 patients who lost
      their implants (average = 20/800) (1 lens status was unknown postdehiscence).
      CONCLUSIONS: Wound dehiscence is a lifelong risk after PK regardless of the age,
      indication for corneal transplant, and time since transplant. A better visual
      outcome was associated with retained pseudophakia and clear corneas.

PMID- 27027916
TI  - Semiautomated SD-OCT Measurements of Corneal Sublayer Thickness in Normal and
      Post-SMILE Eyes.
AB  - PURPOSE: To test the reliability of a novel algorithm for measuring corneal
      epithelial thickness (ET) and stromal thickness of normal eyes and post-small
      incision lenticule extraction (SMILE) corneas with spectral-domain optical
      coherence tomography. METHODS: In this prospective observational study, a
      customized semiautomated software algorithm was developed and applied to measure
      corneal ET and stromal thickness along the horizontal corneal meridian.
      Measurements were performed by 2 examiners in a randomized fashion on a sample of
      40 eyes with previous SMILE for treatment of myopia and a control group composed
      of 40 normal eyes. The intrauser repeatability and interuser reproducibility were
      analyzed by calculating typical indices including the coefficient of variation
      and intraclass correlation coefficient. Corneal sublayer thickness profiles were
      compared between normal and post-SMILE eyes. RESULTS: In both groups,
      coefficients of variation were 3.2% or lower and intraclass correlation
      coefficients were 0.929 or higher indicating excellent reliability of the
      measurement method. Central ET was on an average 6 MUm greater in post-SMILE
      corneas (58.8 +/- 5.4 MUm) compared with normal eyes (52.8 +/- 4.0 MUm), with P <
      0.01. Also, there was greater interindividual variability in ET in post-SMILE
      corneas and their horizontal epithelial profile seemed to show a lenticular
      appearance. CONCLUSIONS: Highly favorable indices of measurement reliability were
      achieved for this novel method of measuring corneal sublayer pachymetry not only
      in normal eyes but also in eyes with previous SMILE. The corneal ET profile was
      significantly altered in post-SMILE eyes compared with normal corneas.

PMID- 27027917
TI  - Case-Control Study of Herpes Simplex Eye Disease: Bronx Epidemiology of Human
      Immunodeficiency Virus Eye Studies.
AB  - PURPOSE: To determine whether human immunodeficiency virus and acquired immune
      deficiency syndrome (HIV/AIDS), diabetes mellitus, and atopic disease are
      associated with herpes simplex virus (HSV) eye disease and to examine the
      characteristics of patients with HIV infection and HSV eye disease. DESIGN:
      Retrospective case-control study. METHODS: A hospital-based control group was
      matched to outpatient visits from June 1, 2010, through May 31, 2014, at
      Montefiore Medical Center (Bronx, NY). Inclusion criteria were a diagnosis of HSV
      eye disease during the study period and residency in the Bronx. Associations
      evaluated included age, sex, HIV/AIDS, diabetes mellitus, and atopic disease.
      RESULTS: HSV eye disease was confirmed in 70 patients, who were compared with 280
      controls. Patients with ocular HSV had a greater prevalence of HIV/AIDS compared
      with controls (8.6% and 2.9%, respectively). Using multivariate analysis to
      control for age and sex, atopic dermatitis [odds ratio (OR) 3.08, 95% confidence
      interval (CI), 0.84-11.20] and diabetes with chronic complications (OR 2.25, 95%
      CI, 0.91-5.61) approached significance, whereas HIV/AIDS (OR 3.37, 95% CI, 1.09
      10.40), an age less than 45 years (OR 2.89, 95% CI, 1.54-5.41), and male sex (OR
      1.85, 95% CI, 1.07-3.18) were significant. In patients with HIV infection and HSV
      eye disease, 3 of 6 (50%) had confirmed AIDS at the time of ocular HSV diagnosis.
      CONCLUSIONS: Patients with HIV infection have more than a 3-fold increased risk
      of developing ocular HSV.

PMID- 27027918
TI  - New Finding in Vernal Keratoconjunctivitis: Splendore-Hoeppli Phenomenon.
AB  - PURPOSE: To report 2 cases of Splendore-Hoeppli phenomenon, a rare
      histopathologic observation, as a late clinical finding in vernal
      keratoconjunctivitis (VKC). METHODS: We report the cases of 2 young women with
      subconjunctival nodules as a manifestation of Splendore-Hoeppli phenomenon with a
      history of severe VKC. RESULTS: After eliminating other conditions causing such a
      reaction, both patients were treated using frequent topical corticosteroid, plus
      topical cyclosporine 2% in one of patient. Complete resolution was observed in
      both patients. CONCLUSIONS: The Splendore-Hoeppli phenomenon could be a part of
      VKC manifestations.

PMID- 27027919
TI  - Epidemiology of Meibomian Gland Dysfunction in an Elderly Population.
AB  - PURPOSE: To study the epidemiology of meibomian gland (MG) dysfunction in an
      elderly, predominantly male population. METHODS: Prospective study of 233
      subjects seen in the Miami Veterans Affairs eye clinic. Patients underwent a
      complete ocular surface examination, including dry eye questionnaires and tear
      assessments (osmolarity, tear breakup time, corneal staining, Schirmer test). The
      main outcome measures were correlations between MG parameters and demographics,
      dry eye symptoms, and tear parameters. The studied MG parameters were eyelid
      vascularity and meibum quality; a score >=2 for either parameter was considered
      abnormal. RESULTS: Mean age of the 233 subjects was 63 years (SD = 11); 91% were
      male and 59% had at least 1 abnormal MG parameter (abnormal quality 55%;
      vascularity 17%). Demographically, patients with abnormal MG parameters were
      significantly older than their counterparts without these findings. Whites were
      more likely to have abnormal eyelid vascularity compared with blacks [n = 36
      (31%) vs. n = 1 (1%), P < 0.0005] but no differences were noted between races
      with respect to meibum quality. Abnormal meibum quality, but not abnormal
      vascularity, was significantly associated with more severe dry eye symptoms.
      Similarly, abnormal meibum quality, but not eyelid vascularity, was significantly
      associated with worse dry eye signs, including decreased tear breakup time and
      increased corneal staining (P < 0.05 for all). CONCLUSIONS: MG dysfunction is a
      frequent finding in an elderly, predominantly male population with racial
      differences noted in the frequency of abnormal eyelid vascularity but not in MG
      quality. Abnormal meibum quality was significantly associated with more severe
      dry eye symptoms and signs.

PMID- 27027920
TI  - Corneal Densitometry: Repeatability in Eyes With Keratoconus and Postcollagen
      Cross-Linking.
AB  - PURPOSE: To assess the repeatability of densitometry, a measure of corneal haze,
      in the control (group I), keratoconic (group II), and postcollagen cross-linking
      (CXL, group III) eyes as measured on Scheimpflug imaging. METHODS: Densitometry
      values for 160 eyes of 160 patients (50 eyes of 50 patients in group I, 50 eyes
      of 50 patients in group II, and 60 eyes of 60 patients in group III) were
      obtained for the 0- to 2-mm, 2- to 6-mm, and 6- to 10-mm zones of the anterior
      (up to 120 MUm), posterior (posterior 60 MUm), and central (between the anterior
      and posterior) cornea. The repeatability of these values was assessed by within
      subject standard deviation, coefficient of repeatability, and coefficient of
      variation. RESULTS: Range of within-subject standard deviation and coefficient of
      variation in the control group (0.2%-0.5% and 2%-4%, respectively) was
      significantly better (less variable) than those in the keratoconus group (0.4%
      0.6% and 3%-5%). The same parameters in the post-CXL group (0.8%-3.8% and 7%-15%)
      were significantly worse (more variable) than that in the other 2 groups. The
      repeatability measures of densitometry were significantly worse in the central 0-
      to 2-mm zone compared with the other 2 zones and for the anterior region compared
      with the central and posterior regions of cornea in all the 3 groups.
      CONCLUSIONS: Consequent to the low repeatability in post-CXL eyes, densitometry
      should be used with caution to gauge response to treatment and visual outcomes in
      treated keratoconus eyes.

PMID- 27027921
TI  - Corneal Cross-Linking for Pediatric Keratoconus: Long-Term Results.
AB  - PURPOSE: To assess the efficacy and safety of cross-linking in pediatric patients
      with keratoconus and to provide a systematic literature overview regarding this
      subject. METHODS: In this prospective cohort, 54 eyes of 36 pediatric patients
      with keratoconus underwent standard epithelium-off cross-linking. Follow-up
      measurements taken up to 5 years after treatment were compared with baseline
      values. Logistic regression was used to identify the underlying cause in case of
      progression despite treatment. Finally, a systematic search was performed in
      PubMed and Embase, and data were extracted and summarized. RESULTS: At all follow
      up visits up to 5 years, maximum keratometry values improved significantly (mean
      change at 5 years -2.06 diopters (D), P = 0.01); moreover, average keratometry,
      uncorrected distance visual acuity, and corrected distance visual acuity improved
      at all follow-up times, though not always to the level of statistical
      significance. In 12 eyes (22%), keratoconus had progressed by >=1.0 D by the last
      follow-up visit, despite corneal cross-linking. Cones that were more
      decentralized were identified as the underlying cause of disease progression. The
      systematic search yielded 17 unique articles: 10 articles on epithelium-off cross
      linking, 2 on accelerated cross-linking, 2 on transepithelial cross-linking, 1 on
      both epithelium-off and transepithelial cross-linking, and 2 on transepithelial
      cross-linking with iontophoresis. CONCLUSIONS: Our long-term follow-up reveals
      that epithelium-off cross-linking is both apparently safe and effective when used
      to prevent keratoconus progression in pediatric patients. However, disease
      progression occurred in 22% of the treated eyes; this progression was attributed
      to a more decentralized cone location.

PMID- 27027922
TI  - Tunable Microwave Absorption Frequency by Aspect Ratio of Hollow
      Polydopamine@alpha-MnO2 Microspindles Studied by Electron Holography.
AB  - A tunable response frequency is highly desirable for practical applications of
      microwave absorption materials but remains a great challenge. Here, hollow
      lightweight polydopamine@alpha-MnO2 microspindles were facilely synthesized with
      the tunable absorption frequency governed by the aspect ratio. The size of the
      hard template is a key factor to achieve the unique shape; the polymer layer with
      uniform thickness plays an important role in obtaining spindles with homogeneous
      size. With the aspect ratio increasing, the maximum reflection loss, as well as
      the absorption bandwidth (<-10 dB), increases and then decreases; meanwhile, the
      microwave absorption band shifts to the low frequency. The optimized aspect ratio
      of the cavity about the hollow polydopamine@alpha-MnO2 microspindles is ~2.8.
      With 3 mm thickness at 9.7 GHz, the strongest reflection reaches -21.8 dB, and
      the width of the absorbing band (<-10 dB) is as wide as 3.3 GHz. Via electron
      holography, it is confirmed that strong charge accumulates around the interface
      between the polydopamine and alpha-MnO2 layers, which mainly contributes to the
      dielectric polarization absorption. This study proposes a reliable strategy to
      tune the absorption frequency via different aspect ratio polymer@alpha-MnO2
      microspindles. 

PMID- 27027923
TI  - Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?
AB  - Peripheral nerve injury continues to be a major global health problem that can
      result in debilitating neurological deficits and neuropathic pain. Current state
      of-the-art treatment involves reforming the damaged nerve pathway using a nerve
      autograft. Engineered nerve repair conduits can provide an alternative to the
      nerve autograft avoiding the inevitable tissue damage caused at the graft donor
      site. Commercially available nerve repair conduits are currently only considered
      suitable for repairing small nerve lesions; the design and performance of
      engineered conduits requires significant improvements to enable their use for
      repairing larger nerve defects. Carbon nanotubes (CNTs) are an emerging novel
      material for biomedical applications currently being developed for a range of
      therapeutic technologies including scaffolds for engineering and interfacing with
      neurological tissues. CNTs possess a unique set of physicochemical properties
      that could be useful within nerve repair conduits. This progress report aims to
      evaluate and consolidate the current literature pertinent to CNTs as a
      biomaterial for supporting peripheral nerve regeneration. The report is presented
      in the context of the state-of-the-art in nerve repair conduit design; outlining
      how CNTs may enhance the performance of next generation peripheral nerve repair
      conduits.

PMID- 27027925
TI  - Kinetics versus Thermodynamics in Virus Capsid Polymorphism.
AB  - Virus coat proteins spontaneously self-assemble into empty shells in aqueous
      solution under the appropriate physicochemical conditions, driven by an
      interaction free energy per bond on the order of 2-5 times the thermal energy
      kBT. For this seemingly modest interaction strength, each protein building block
      nonetheless gains a very large binding free energy, between 10 and 20 kBT.
      Because of this, there is debate about whether the assembly process is reversible
      or irreversible. Here we discuss capsid polymorphism observed in in vitro
      experiments from the perspective of nucleation theory and of the thermodynamics
      of mass action. We specifically consider the potential contribution of a
      curvature free energy term to the effective interaction potential between the
      proteins. From these models, we propose experiments that may conclusively reveal
      whether virus capsid assembly into a mixture of polymorphs is a reversible or an
      irreversible process.

PMID- 27027926
TI  - Effect of the three-dimensional organization of liver cells on the biogenesis of
      the gamma-glutamyltransferase fraction pattern.
AB  - Context Four gamma-glutamyltransferase (GGT) fractions with different molecular
      weights (big-, medium-, small- and free-GGT) are detectable in human plasma.
      Objective Verify if liver cells can release all four GGT fractions and if the
      spatial cell organization influences their release. Methods Hepatoma (HepG2) and
      melanoma (Me665/2/60) cells were cultured as monolayers or spheroids. GGT
      released in culture media was analysed by gel-filtration chromatography. Results
      HepG2 and Me665/2/60 monolayers released the b-GGT fraction, while significative
      levels of s-GGT and f-GGT were detectable only in media of HepG2-spheroids. Bile
      acids alone or in combination with papain promoted the conversion of b-GGT in s
      GGT or f-GGT, respectively. Conclusions GGT is usually released as b-GGT, while s
      GGT and f-GGT are likely to be produced in the liver extracellular environment by
      the combined action of bile acids and proteases. 

PMID- 27027928
TI  - The vertebrate Hox gene regulatory network for hindbrain segmentation: Evolution
      and diversification: Coupling of a Hox gene regulatory network to hindbrain
      segmentation is an ancient trait originating at the base of vertebrates.
AB  - Hindbrain development is orchestrated by a vertebrate gene regulatory network
      that generates segmental patterning along the anterior-posterior axis via Hox
      genes. Here, we review analyses of vertebrate and invertebrate chordate models
      that inform upon the evolutionary origin and diversification of this network.
      Evidence from the sea lamprey reveals that the hindbrain regulatory network
      generates rhombomeric compartments with segmental Hox expression and an
      underlying Hox code. We infer that this basal feature was present in ancestral
      vertebrates and, as an evolutionarily constrained developmental state, is
      fundamentally important for patterning of the vertebrate hindbrain across diverse
      lineages. Despite the common ground plan, vertebrates exhibit neuroanatomical
      diversity in lineage-specific patterns, with different vertebrates revealing
      variations of Hox expression in the hindbrain that could underlie this
      diversification. Invertebrate chordates lack hindbrain segmentation but exhibit
      some conserved aspects of this network, with retinoic acid signaling playing a
      role in establishing nested domains of Hox expression.

PMID- 27027927
TI  - Nitrodibenzofuran: A One- and Two-Photon Sensitive Protecting Group That Is
      Superior to Brominated Hydroxycoumarin for Thiol Caging in Peptides.
AB  - Photoremovable protecting groups are important for a wide range of applications
      in peptide chemistry. Using Fmoc-Cys(Bhc-MOM)-OH, peptides containing a Bhc
      protected cysteine residue can be easily prepared. However, such protected thiols
      can undergo isomerization to a dead-end product (a 4-methylcoumarin-3-yl
      thioether) upon photolysis. To circumvent that photoisomerization problem, we
      explored the use of nitrodibenzofuran (NDBF) for thiol protection by preparing
      cysteine-containing peptides where the thiol is masked with an NDBF group. This
      was accomplished by synthesizing Fmoc-Cys(NDBF)-OH and incorporating that residue
      into peptides by standard solid-phase peptide synthesis procedures. Irradiation
      with 365 nm light or two-photon excitation with 800 nm light resulted in
      efficient deprotection. To probe biological utility, thiol group uncaging was
      carried out using a peptide derived from the protein K-Ras4B to yield a sequence
      that is a known substrate for protein farnesyltransferase; irradiation of the
      NDBF-caged peptide in the presence of the enzyme resulted in the formation of the
      farnesylated product. Additionally, incubation of human ovarian carcinoma (SKOV3)
      cells with an NDBF-caged version of a farnesylated peptide followed by UV
      irradiation resulted in migration of the peptide from the cytosol/Golgi to the
      plasma membrane due to enzymatic palmitoylation. Overall, the high cleavage
      efficiency devoid of side reactions and significant two-photon cross-section of
      NDBF render it superior to Bhc for thiol group caging. This protecting group
      should be useful for a plethora of applications ranging from the development of
      light-activatable cysteine-containing peptides to the development of light
      sensitive biomaterials.

PMID- 27027929
TI  - Efficacy, acceptability and cost effectiveness of four therapeutic agents for
      treatment of scabies.
AB  - The aim of this study is to evaluate four drug regimens for treatment of scabies
      as regard their efficacy, acceptability and cost effectiveness. Two hundred cases
      with ordinary scabies were randomized into four groups. First group received
      ivermectin 200 MUg/kg body weight single oral dose, repeated after one week. The
      second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5%
      lotion, whereas the fourth group received 5-10% sulfur ointment. Topical
      treatments were applied for five consecutive nights. Patients were followed up
      for two weeks for cure rate and adverse effects. At the end of the study,
      permethrin provided a significant efficacy of 88% and acceptability in 100% of
      cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided
      efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper
      cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest
      drug. Sulfur ointment provided the least rates, and it was the most expensive.
      Treatment choice will depend on the age, the general condition of cases, patient
      compliance to topical treatment and his ability to stick to its roles, and the
      economic condition of the patient. 

PMID- 27027930
TI  - Quantitative mapping of collagen fiber alignment in thick tissue samples using
      transmission polarized-light microscopy.
AB  - Immersion optical clearing makes it possible to use transmission polarized-light
      microscopy for characterization of thick (200 to 2000  MUm) layers of biological
      tissues. We discuss polarization properties of thick samples in the context of
      the problem of characterization of collagen fiber alignment in connective tissues
      such as sclera and dermis. Optical chirality caused by azimuthal variations of
      the macroscopic (effective) optic axis of the medium across the sample thickness
      should be considered in polarization mapping of thick samples of these tissues.
      We experimentally evaluate to what extent the optical chirality affects the
      measurement results in typical situations and show under what conditions it can
      be easily taken into account and does not hinder, but rather helps, in
      characterization of collagen fiber alignment.

PMID- 27027931
TI  - Solving Multiple Isolated, Interleaved, and Blended Tasks through Modular
      Neuroevolution.
AB  - Many challenging sequential decision-making problems require agents to master
      multiple tasks. For instance, game agents may need to gather resources, attack
      opponents, and defend against attacks. Learning algorithms can thus benefit from
      having separate policies for these tasks, and from knowing when each one is
      appropriate. How well this approach works depends on how tightly coupled the
      tasks are. Three cases are identified: Isolated tasks have distinct semantics and
      do not interact, interleaved tasks have distinct semantics but do interact, and
      blended tasks have regions where semantics from multiple tasks overlap. Learning
      across multiple tasks is studied in this article with Modular Multiobjective
      NEAT, a neuroevolution framework applied to three variants of the challenging Ms.
      Pac-Man video game. In the standard blended version of the game, a surprising,
      highly effective machine-discovered task division surpasses human-specified
      divisions, achieving the best scores to date in this game. In isolated and
      interleaved versions of the game, human-specified task divisions are also
      successful, though the best scores are surprisingly still achieved by machine
      discovery. Modular neuroevolution is thus shown to be capable of finding useful,
      unexpected task divisions better than those apparent to a human designer. 

PMID- 27027932
TI  - Comparison of Dilation Methods in Percutaneous Nephrolithotomy: Which One Is More
      Successful?
AB  - OBJECTIVE: Creation of the access tract is an important step in percutaneous
      nephrolithotomy (PNL). In this study, we compared the efficiency and safety of
      Amplatz, Alken, and balloon dilation methods in the creation of the access tract.
      MATERIALS AND METHODS: Data from 487 PNL patients admitted to 517 renal units in
      3 centers were analyzed. The Amplatz (280 patients), Alken (142 patients), and
      balloon (95 patients) dilation methods were compared for their success, duration
      of the dilation, injury to the collecting system, durations of fluoroscopy and
      surgery, stone-free and complication rates, pre- and postoperative hematocrit
      levels, and need for blood transfusion. RESULTS: The dilation methods did not
      significantly differ with respect to patient demographic data, mean stone area,
      decrease in hematocrit, need for blood transfusion, unsuccessful tract dilation,
      injury to the collecting system, stone-free rate, and rate of postoperative
      complications. The mean fluoroscopy times during Amplatz, Alken, and balloon
      dilation were 288.52 +/- 164.67, 287.34 +/- 164.99, and 169.23 +/- 21 seconds,
      respectively. The mean duration of surgery was 96.48 +/- 46.07, 94.72 +/- 42.25,
      and 78 +/- 25.96 minutes, respectively. The duration of tract creation was 328.67
      +/- 172.99, 325.14 +/- 175.70, and 203.50 +/- 32.76 seconds, respectively. The
      durations of surgery and tract creation were significantly shorter in the balloon
      dilation group. CONCLUSION: None of the dilation methods was significantly
      superior in terms of surgical success, efficiency, or safety. Although balloon
      dilation was advantageous with respect to time parameters, the role of surgical
      experience should not be ignored.

PMID- 27027933
TI  - The application of halloysite tubule nanoclay in drug delivery.
AB  - INTRODUCTION: Natural and biocompatible clay nanotubes are among the best
      inorganic materials for drug nanoformulations. These halloysite tubes with SiO2
      on the outermost surface have diameter of ca. 50 nm, length around 1 micrometer
      and may be loaded with drugs at 10-30 wt. %. Narrow tube openings allow for
      controllable sustained drug release for hours, days or even weeks. AREAS COVERED:
      Physical-chemical properties of these nanotubes are described followed by
      examples of drug-loading capabilities, release characteristics, and control of
      duration of release through the end tube capping with polymers. Development of
      halloysite-polymer composites such as tissue scaffolds and bone cement/dentist
      resin formulations with enhanced mechanical properties and extension of the drug
      release to 2-3 weeks are described. Examples of the compression properties of
      halloysite in tablets and capsules are also shown. EXPERT OPINION: We expect that
      clay nanotubes will be used primarily for non-injectable drug formulations, such
      as topical and oral dosage forms, cosmetics, as well as for composite materials
      with enhanced therapeutic effects. These include tissue scaffolds, bone cement
      and dentist resins with sustained release of antimicrobial and cell growth
      promoting medicines (including proteins and DNA) as well as other formulations
      such as compounds for antiseptic treatment of hospitals.

PMID- 27027934
TI  - Acute non-traumatic gastrothorax: presentation of a case with chest pain and
      atypical radiologic findings.
AB  - A previously well 71-year-old woman presented to the Emergency Department with
      acute-onset left-sided chest pain. She was haemodynamically stable with
      unremarkable systemic examination. Her electrocardiogram and troponin were within
      normal limits and her chest radiograph showed a raised left hemi-diaphragm. Two
      hours after admission, this woman became acutely breathless, and suffered a
      pulseless electrical activity cardiac arrest. After cardiopulmonary
      resuscitation, there was a return of spontaneous circulation and regained
      consciousness. A repeat clinical assessment revealed a new left-sided dullness to
      percussion with contralateral percussive resonance on respiratory examination.
      CXR revealed a left pan-hemi-thoracic opacity whilst better definition using CT
      pulmonary angiography (CTPA) indicated an acute tension gastrothorax secondary to
      a large left-sided diaphragmatic hernia. Nasogastric (NG) tube insertion was used
      to decompress the stomach and the patient underwent uncomplicated emergency
      laparoscopic hernia reduction. She remained well at 1-year follow-up. 

PMID- 27027935
TI  - Visual Attention to Dynamic Scenes of Ambiguous Provocation and Children's
      Aggressive Behavior.
AB  - Research on biases in attention related to children's aggression has yielded
      mixed results. Some research suggests that inattention to social cues and
      reliance on maladaptive social schemas underlie aggression. Other research
      suggests that maladaptive social schemas lead aggressive individuals to attend to
      nonhostile cues. The primary objective of this study was to test the proposition
      that aggression is related to delayed attention to cues followed by selective
      attention to nonhostile cues after the provocation has occurred. A second
      objective was to test whether these biases are associated with aggression only
      when children hold negative social schemas. The eye fixations of 70 children (34
      boys, 36 girls; Mage = 11.71 years) were monitored with an eye tracker as they
      watched video clips of child actors portraying scenes of ambiguous provocation.
      Aggression was measured using peer-, teacher-, and parent-reports, and children
      completed a measure of antisocial and prosocial peer beliefs. Aggressive behavior
      was associated with greater time until fixation on the provocateur among youth
      who held antisocial peer beliefs. Aggression was also associated with greater
      time until fixation on an actor displaying empathy for the victim among children
      reporting low levels of prosocial peer beliefs. After the provocation, aggression
      was associated with suppressed attention to an amused peer among children who
      held negative peer beliefs. Increasing attention to cues in a scene of ambiguous
      provocation, in conjunction with fostering more positive beliefs about peers, may
      be effective in reducing hostile responding among aggressive youth.

PMID- 27027936
TI  - Temporal effects of Notch signaling and potential cooperation with multiple
      downstream effectors on adenohypophysis cell specification in zebrafish.
AB  - The adenohypophysis (AH) consists of six distinct types of hormone-secreting
      cells. In zebrafish, although proper differentiation of all AH cell types has
      been shown to require Notch signaling within a period of 14-16 h
      postfertilization (hpf), the mechanisms underlying this process remain to be
      elucidated. Herein, we observed using the Notch inhibitor dibenzazepine (DBZ)
      that Notch signaling also contributed to AH cell specification beyond 16 hpf.
      Specification of distinct cell types was perturbed by DBZ treatment for different
      time frames, suggesting that AH cells are specified by Notch-dependent and cell
      type-specific mechanisms. We also found that two hes-family genes, her4.1 and
      hey1, were expressed in the developing AH under the influence of Notch signaling.
      her4.1 knockdown reduced expression of proopiomelanocortin a (pomca), growth
      hormone (gh), and prolactin, whereas hey1 was responsible only for gh expression.
      Simultaneous loss of both Her4.1 and Hey1 produced milder phenotypes than that of
      DBZ-treated embryos. Moreover, DBZ treatment from 18 hpf led to a significant
      down-regulation of both gh and pomca genes only when combined with injection of a
      subthreshold level of her4.1-morpholino. These observations suggest that multiple
      downstream effectors, including Her4.1 and Hey1, mediate Notch signaling during
      AH cell specification. 

PMID- 27027937
TI  - Nasal Microbiome Composition Is Associated with Chitotriosidase (Chit1) Activity
      in Adult Hutterites.

PMID- 27027938
TI  - Genetic Variation in Surfactant Protein-A2 Results in Altered Regulation of
      Eosinophil Activities and Enhanced Eosinophilia in Patients with Asthma.

PMID- 27027939
TI  - Antisense MicroRNA Therapy of Airway Remodeling in House Dust Mite-sensitized
      Mice.

PMID- 27027940
TI  - Longitudinally Stable, Clinically Defined Clusters of Patients with Asthma
      Independently Identified in the ADEPT and U-BIOPRED Asthma Studies.
AB  - BACKGROUND: ADEPT (Airways Disease Endotyping for Personalized Therapeutics) and
      U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome
      Consortium) are independent asthma biomarker studies that aim to enable
      personalization of therapies. METHODS: Patients in both studies were identified
      by similar criteria, and similar clinical parameters and biomarkers were assessed
      in blood, sputum, and airway samples. Fuzzy partition-around-medoid clustering
      was performed on the ADEPT dataset (n = 154) and independently on the U-BIOPRED
      asthma dataset (n = 82), filtered to match ADEPT inclusion criteria. For both
      studies, the same eight easily measurable clinical variables were used, and ADEPT
      also included methacholine airway hyperresponsiveness. Models for cluster
      classification probabilities were derived and applied to the 12-month
      longitudinal ADEPT data and the full U-BIOPRED adult asthma dataset (n = 397) as
      independent external validation. MEASUREMENTS AND MAIN RESULTS: Four clusters
      were identified in the ADEPT-asthma study population with distinct clinical and
      biomarker profiles. In general, Cluster 1 consists of patients with mild asthma
      not treated with steroids and well controlled with preserved lung function and a
      low-inflammatory phenotype; Cluster 2 is partially controlled, with mild airflow
      obstruction but severe airway hyperresponsiveness and a Th2 phenotype (brittle
      phenotype); Cluster 3 is partially controlled with mild airflow obstruction but
      reduced vital capacity, less bronchodilator reversibility, and a non-Th2
      phenotype with neutrophilic inflammation (chronic obstructive pulmonary disease
      like); and Cluster 4 is poorly controlled, with marked airflow obstruction,
      marked bronchodilator reversibility, and a mixed inflammatory phenotype. Overall,
      the ADEPT clusters were stable over 12 months and reproduced by identifying four
      analogous clusters in the U-BIOPRED asthma dataset, with distributions for most
      clustering and nonclustering variables similar to ADEPT. CONCLUSIONS: We report
      four clinical clusters in ADEPT and confirmed these by external validation in U
      BIOPRED. The ADEPT clusters have distinct clinical and molecular characteristics,
      are stable over 12 months, and present opportunities for the development of
      tailored therapeutics for asthma.

PMID- 27027942
TI  - Severe Asthma in Pediatric Patients. Pathophysiology and Unmet Needs.
AB  - Recent statistics have shown that asthma deaths and hospitalizations are
      decreasing, but there are unmet challenges in the management of severe asthma in
      children. Current asthma management is focused on achieving asthma control
      through an effort to minimize asthma impairment via specifically addressing
      factors that affect day-to-day symptoms, and minimizing the risk of future asthma
      related events, such as asthma exacerbations, disease progression, and adverse
      effects to medications. New targeted medications have been developed for which
      therapeutic responses have been correlated with specific biomarkers; for example,
      sputum or blood eosinophil count with anti-IL-5 therapy and serum periostin with
      anti-IL-13 therapy. These drugs hold great promise, but will likely be expensive
      alternatives to traditional asthma therapy. There is a growing need to address
      the age-specific challenges in the management of subjects with asthma from the
      young to the very old. In the future, it will be important to develop strategies
      to prevent the development of asthma and, in children with the disease, to
      maximize the appropriate use of, and adherence to, the available medications
      before considering more expensive alternatives. To do this, we will need to
      standardize and harmonize medical care, while improving communication and setting
      up systems of collaboration. If executed effectively, this effort should have a
      marked impact on reducing the prevalence of asthma in the future and the
      consequent burden of asthma on society. 

PMID- 27027941
TI  - Compressive Stress Causes an Unjamming Transition and an Epithelial-Mesenchymal
      Transition in the Airway Epithelium in Asthma.

PMID- 27027943
TI  - Cistrome Analysis of Glucocorticoid Receptor Activity in Bronchial Epithelial
      Cells Defines Novel Mechanisms of Steroid Efficacy.

PMID- 27027944
TI  - Massively Parallel Identification of Regulatory Variants in Asthma.

PMID- 27027945
TI  - Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical
      Phenotypes of Asthma.
AB  - INTRODUCTION: It is increasingly recognized that asthma is a heterogeneous
      disease. Therefore, it is possible that analysis of gene expression in the airway
      will reveal clinically meaningful transcriptional endotypes of asthma (TEA
      clusters). METHODS: We measured whole transcriptome gene expression profiles in
      the sputum and whole blood of 100 individuals with asthma and 12 control subjects
      using the Affymetrix HuGene ST 1.0 gene arrays. Unsupervised clustering was
      conducted using pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG).
      This identified three TEA clusters that were correlated with clinical,
      physiologic, and inflammatory characteristics of the disease. TEA cluster 1 is a
      cluster of patients with asthma with a significantly higher rate of intubation (P
      = 0.05), a lower prebronchodilator FEV1 (P = 0.006), a higher bronchodilator
      response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04) than the
      other two TEA clusters. TEA cluster 2 has a higher rate of hospitalization for
      asthma (P = 0.04) and is heterogeneous. TEA cluster 3 is the largest cluster and
      has normal lung function, low exhaled nitric oxide levels, and lower inhaled
      steroid requirements. TEA cluster 1 had the highest sputum Th2 gene signature (IL
      4, -5, and -13) compared with the other clusters. A classifier was developed that
      predicts TEA cluster assignment using 53 predictive genes in the circulation. The
      classifier was applied to gene expression data of children from the Asthma
      Biorepository for Integrative Genomic Exploration (Asthma BRIDGE) consortium
      cohort and confirmed that TEA clusters 1 and 2 are associated with history of
      intubation (P = 5.58 * 10(-06)) and hospitalization (P = 0.01), respectively.
      CONCLUSIONS: Analysis of the sputum transcriptome reveals three TEA clusters with
      different clinical and physiologic characteristics of disease in children and
      adults with asthma. This suggests that there are common transcriptomic signatures
      in the blood in children and adults with asthma that are associated with features
      of severe asthma.

PMID- 27027946
TI  - List of Posters Presented at the 58th Thomas L. Petty Aspen Lung Conference.

PMID- 27027947
TI  - Introduction to the 58th Annual Thomas L. Petty Aspen Lung Conference: Asthma
      2015: Mechanisms to Personalized Medicine.

PMID- 27027948
TI  - Allergen-Specific CD4(+) T Cells in Human Asthma.
AB  - In allergic asthma, aeroallergen exposure of sensitized individuals mobilizes
      robust innate and adaptive airway immune responses, stimulating eosinophilic
      airway inflammation and the activation and infiltration of allergen-specific
      CD4(+) T cells into the airways. Allergen-specific CD4(+) T cells are thought to
      be central players in the asthmatic response as they specifically recognize the
      allergen and initiate and orchestrate the asthmatic inflammatory response. In
      this article, we briefly review the role of allergen-specific CD4(+) T cells in
      the pathogenesis of human allergic airway inflammation in allergic individuals,
      discuss the use of allergen-major histocompatibility complex class II tetramers
      to characterize allergen-specific CD4(+) T cells, and highlight current gaps in
      knowledge and directions for future research pertaining to the role of allergen
      specific CD4(+) T cells in human asthma. 

PMID- 27027949
TI  - Lung Macrophage Diversity and Asthma.
AB  - Macrophages (MPs) are one of the most prominent leukocyte populations in the lung
      and, in many ways, a forgotten player in asthma pathogenesis. Diverse functions
      in asthma initiation and maintenance in chronic disease have been demonstrated,
      which has led to confusion as to if pulmonary MPs are agents of good or evil in
      asthma. Much of this is due to the wide diversity of MP populations in the lung,
      many of which are inaccessible experimentally in most clinical studies. This
      review frames lung MP biology in the context of location, phenotype, function,
      and response phase in asthma pathogenesis. It also assesses new findings
      regarding MP diversity that have challenged old dogmas and generates new ways to
      understand how MPs function. 

PMID- 27027950
TI  - New Insights in Oxidant Biology in Asthma.
AB  - Research over the past 30 years has identified mechanistic biochemical oxidation
      pathways that contribute to asthma pathophysiology. Redox imbalance is present in
      asthma and strongly linked to the pathobiology of airflow obstruction, airway
      hyperreactivity, and remodeling. High levels of reactive oxygen species, reactive
      nitrogen species, and oxidatively modified proteins in the lung, blood, and urine
      provide conclusive evidence for pathologic oxidation in asthma. Concurrent loss
      of antioxidants, such as superoxide dismutases and catalase, is attributed to
      redox modifications of the enzymes, and further amplifies the oxidative injury in
      the airway. The presence of high levels of urine bromotyrosine, an oxidation
      product of eosinophil peroxidase, identifies activated eosinophils, and shows
      promise for use as a noninvasive biomarker of poor asthma control. 

PMID- 27027952
TI  - Epigenetic Mechanisms in Asthma.
AB  - Asthma and allergic diseases are among the most prevalent chronic noncommunicable
      diseases of childhood, but the underlying pathogenetic mechanisms are poorly
      understood. Because epigenetic mechanisms link gene regulation to environmental
      cues and developmental trajectories, their contribution to asthma and allergy
      pathogenesis is under active investigation. DNA methylation signatures associated
      with concurrent disease and with the development of asthma during childhood
      asthma have been identified, but their significance is not easily interpretable.
      On the other hand, the characterization of early epigenetic predictors of asthma
      points to a potential role of epigenetic mechanisms in regulating the inception
      of, and the susceptibility to, this disease. 

PMID- 27027951
TI  - Autophagy: Friend or Foe in Lung Disease?
AB  - Autophagy is a highly conserved process by which cells can recycle organelles and
      proteins by degrading them in the lysosomes. Although autophagy is considered a
      dynamic system responsible for cellular renovation and homeostasis under
      physiological conditions, it is increasingly clear that autophagy is directly
      relevant to clinical disease. During disease progression, autophagy not only
      serves as a cellular protective mechanism but also can represent a harmful event
      under certain conditions. In addition, although autophagy can act as a
      nonselective bulk degradation process, recent research shows that autophagy can
      selectively degrade specific proteins, organelles, and invading bacteria, in
      processes termed "selective autophagy." Selective autophagy has drawn the
      attention of researchers because of its potential importance in clinical
      diseases. In this article, we outline the most recent studies implicating
      autophagy and selective autophagy in human lung diseases, including chronic
      obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary
      fibrosis, and sepsis. We also discuss the relationship between autophagy and
      other molecular mechanisms related to disease progression, including programmed
      necrosis (necroptosis) and the inflammasome, an inflammatory signaling platform
      that regulates the secretion of IL-1beta and IL-18. Finally, we examine the dual
      nature of autophagy and selective autophagy in the lung, which have both
      protective and injurious effects for human lung disease. 

PMID- 27027953
TI  - Gut Microbiota and Allergic Disease. New Insights.
AB  - The rapid rise in childhood allergies (atopy) in Westernized nations has
      implicated associated environmental exposures and lifestyles as primary drivers
      of disease development. Culture-based microbiological studies indicate that atopy
      has demonstrable ties to altered gut microbial colonization in very early life.
      Infants who exhibit more severe multisensitization to food- or aero-allergens
      have a significantly higher risk of subsequently developing asthma in childhood.
      Hence an emerging hypothesis posits that environment- or lifestyle-driven
      aberrancies in the early-life gut microbiome composition and by extension,
      microbial function, represent a key mediator of childhood allergic asthma. Animal
      studies support this hypothesis. Environmental microbial exposures
      epidemiologically associated with allergy protection in humans confer protection
      against airway allergy in mice. In addition, gut microbiome-derived short-chain
      fatty acids produced from a high-fiber diet have been shown to protect against
      allergy via modulation of both local and remote mucosal immunity as well as
      hematopoietic antigen-presenting cell populations. Here we review key data
      supporting the concept of a gut-airway axis and its critical role in childhood
      atopy. 

PMID- 27027954
TI  - Airway Epithelial Orchestration of Innate Immune Function in Response to Virus
      Infection. A Focus on Asthma.
AB  - Asthma is a very common respiratory condition with a worldwide prevalence
      predicted to increase. There are significant differences in airway epithelial
      responses in asthma that are of particular interest during exacerbations.
      Preventing exacerbations is a primary aim when treating asthma because they often
      necessitate unscheduled healthcare visits and hospitalizations and are a
      significant cause of morbidity and mortality. The most common cause of asthma
      exacerbations is a respiratory virus infection, of which the most likely type is
      rhinovirus infection. This article focuses on the role played by the epithelium
      in orchestrating the innate immune responses to respiratory virus infection.
      Recent studies show impaired bronchial epithelial cell innate antiviral immune
      responses, as well as augmentation of a pro-Th2 response characterized by the
      epithelial-derived cytokines IL-25 and IL-33, crucial in maintaining the Th2
      cytokine response to virus infection in asthma. A better understanding of the
      mechanisms of these abnormal immune responses has the potential to lead to the
      development of novel therapeutic targets for virus-induced exacerbations. The aim
      of this article is to highlight current knowledge regarding the role of viruses
      and immune modulation in the asthmatic epithelium and to discuss exciting areas
      for future research and novel treatments. 

PMID- 27027955
TI  - Cell Jamming in the Airway Epithelium.
AB  - Hallmarks of asthma include chronic airway inflammation, progressive airway
      remodeling, and airway hyperresponsiveness. The initiation and perpetuation of
      these processes are attributable at least in part to critical events within the
      airway epithelium, but the underlying mechanisms remain poorly understood. New
      evidence now suggests that epithelial cells derived from donors without asthma
      versus donors with asthma, even in the absence of inflammatory cells or
      mediators, express modes of collective migration that innately differ not only in
      the amount of migration but also in the kind of migration. The maturing cell
      layer tends to undergo a transition from a hypermobile, fluid-like, unjammed
      phase in which cells readily rearrange, exchange places, and flow, to a
      quiescent, solid-like, jammed phase in which cells become virtually frozen in
      place. Moreover, the unjammed phase defines a phenotype that can be perpetuated
      by the compressive stresses caused by bronchospasm. Importantly, in cells derived
      from donors with asthma versus donors without asthma, this jamming transition
      becomes substantially delayed, thus suggesting an immature or dysmature
      epithelial phenotype in asthma. 

PMID- 27027956
TI  - Severe Asthma: Have We Made Progress?
AB  - Tremendous efforts have been invested in research to (1) discover risk factors,
      biomarkers, and clinical characteristics; (2) understand the pathophysiology and
      treatment response variability in severe asthma; and (3) design new therapies.
      However, to combat severe asthma, many questions concerning the pathogenesis of
      severe asthma, including its natural history, genetic and environmental risk
      factors, and disease mechanisms, must be answered. In this article we highlight
      some of the major discoveries concerning the pathogenesis of severe asthma and
      its therapeutic development. We conclude that discoveries on numerous fronts of
      severe asthma, from disease heterogeneity, features of airway remodeling,
      cytokine mediators and signaling pathways underlying disease pathogenesis,
      disease mechanisms, potential biomarkers, to new therapeutic targets, demonstrate
      that progress has been made in understanding and developing more effective
      treatments for this difficult-to-treat disease. 

PMID- 27027957
TI  - Asthma Was Talking, But We Weren't Listening. Missed or Ignored Signals That Have
      Slowed Treatment Progress.
AB  - The discovery that eosinophilia and steroid responsiveness are dominant signals
      in patients with asthma led to the conclusion that inflammation characterized by
      up-regulation of the type 2 cytokines that mediate eosinophilia (IL -4, -5, and 
      13) (type 2 inflammation) is central to asthma pathogenesis in all patients and
      resulted in a singular emphasis on animal models of type 2 inflammation to
      unravel disease mechanisms. This in turn led to great progress in identifying
      drug targets and in developing inhibitors of type 2 inflammation. Despite this
      significant and clinically important progress, there has been a growing body of
      evidence that airway type 2 inflammation is not a ubiquitous pathologic feature
      of asthma and a growing acceptance that the type 2-centric asthma paradigm has
      held back understanding of mechanisms of disease in patients who do not have type
      2 inflammation (helper T-cell type 2 [Th2]-low asthma). This "tyranny of the
      dominant paradigm" effect means that asthma clinicians have no effective
      controller treatments to offer their many patients with Th2-low asthma. It also
      means that asthma researchers are struggling to understand the mechanisms of
      disease that operate in Th2-low asthma and how these mechanisms might be modeled
      in vitro and in vivo to identify novel drug targets and provide a broader range
      of asthma treatments. 

PMID- 27027958
TI  - Drug Development and Biologics in Asthma. A New Era.
AB  - Considerable progress has been made toward developing targeted biological
      therapeutics for asthma, due in large part to a deeper understanding of asthma
      pathophysiology. This explosion of knowledge has revealed asthma to be a much
      more complex and heterogeneous entity than previously understood. The
      identification of particular asthma phenotypes with distinct pathophysiologic
      mechanisms has opened up a new era for patient populations not well served by
      current therapies, especially patients with severe asthma. 

PMID- 27027960
TI  - Beyond the Paradigm of Asthma as an Inflammatory Disease. A Summary of the 2015
      Aspen Lung Conference.

PMID- 27027959
TI  - Asthma Genetics in the Post-GWAS Era.
AB  - Genome-wide association studies (GWAS) of asthma have yielded exciting results
      and identified novel risk alleles and loci. But, like other common complex
      diseases, asthma-associated alleles have small effect sizes and account for
      little of the prevalence of asthma. In this review, I discuss the limitations of
      GWAS approaches and the major challenges facing geneticists in the post-GWAS era
      and propose alternative strategies to address these challenges. In particular, I
      propose that focusing on genetic variations that influences gene expression and
      using cell models of gene-environment interactions in cell types that are
      relevant to asthma will allow us to more completely characterize the genetic
      architecture of asthma. 

PMID- 27027961
TI  - Mechanisms to Suppress ILC2-induced Airway Inflammation.
AB  - Epithelial cell-derived cytokines such as IL-33 and IL-25 activate group 2 innate
      lymphoid cells (ILC2s), which are known to be important sources of type 2
      cytokines such as IL-5 and IL-13 in a variety of asthma mouse models. Recently,
      human studies have also reported the involvement of ILC2s in asthma, as ILC2s are
      increased in peripheral blood and bronchoalveolar lavage fluid in patients with
      asthma. Compared with positive regulators such as IL-25 and IL-33, the mechanisms
      to suppress the ILC2s-induced inflammation remain unclear. Because ILC2s express
      various cytokine receptors, the function of ILC2s would likely be influenced by
      cytokines present around ILC2s in the lungs. We reported that IL-2, IL-7, and
      thymic stromal lymphopoietin (TSLP) induced phosphorylation of signal transducer
      and activator of transcription 5 (STAT5) and promoted the proliferation of ILC2s
      and type 2 cytokine production when combined with IL-33. TSLP enhanced the
      expression of Bcl-xL, an antiapoptotic molecule, and caused corticosteroid
      resistant airway inflammation via ILC2s in mice. Furthermore, pimozide, a STAT5
      inhibitor, counteracted the TSLP-induced corticosteroid resistance and suppressed
      airway inflammation. As a negative regulator, we have found that IFN-gamma and IL
      27 suppressed the proliferation and type 2 cytokine production of ILC2s in vitro
      and in vivo. Interestingly, ILC2s-induced eosinophilic inflammation was more
      severe in IFN-gamma receptor-deficient mice than in control mice. These findings
      suggest the importance of environmental cytokines for the regulation of ILC2s,
      and this would lead to a new approach to control airway inflammation in asthma. 

PMID- 27027962
TI  - T-Cell Immunophenotyping of Second-Hand Smoke-related Asthma.

PMID- 27027963
TI  - Effect of IL-37 on Allergic Airway Inflammation.
AB  - RATIONALE: The new cytokine IL-37 has been described as a negative regulator of
      innate immunity. It reduces activation of dendritic cells and the production of
      proinflammatory mediators in murine and human immune cells. Although recent
      results from the CLARA childhood asthma cohort suggested an impact of IL-37 on
      human asthma pathogenesis, the receptor for IL-37 and its implication in adaptive
      immune responses have not been determined. OBJECTIVES: This study aimed to
      clarify whether IL-37 also provides antiinflammatory effects on adaptive immune
      responses and through which receptor it exerts its effects. METHODS: IL-37 levels
      in supernatants of restimulated peripheral blood mononuclear cells isolated from
      children with asthma and healthy children were determined. Mice (wild-type, IL
      18Ralpha(-/-), and SIGIRR/IL-1R8(-/-)) were sensitized to ovalbumin (OVA) and
      challenged with OVA aerosol to induce acute allergic experimental asthma, and IL
      37 was applied intranasally during OVA challenge. Airway hyperresponsiveness was
      determined. A cytometric bead array was used to assess cytokine levels in
      bronchoalveolar lavage fluid. Epithelial mucus was quantified on the basis of
      lung sections stained with periodic acid-Schiff reagent, using the newCAST
      microscope system. MEASUREMENTS AND MAIN RESULTS: Human peripheral blood
      mononuclear cells of subjects with allergic asthma produce less IL-37 compared
      with healthy control subjects. In mice, intranasal administration of IL-37
      dampened allergic airway inflammation as well as proinflammatory cytokine
      production, mucus hyperproduction, and airway hyperresponsiveness. However, the
      antiinflammatory effects of IL-37 were completely abolished in mice deficient for
      IL-18Ralpha or SIGIRR/IL-1R8. CONCLUSIONS: This study demonstrates that IL-37
      reduces allergic airway inflammation directed by type 2 helper T cells and the
      hallmarks of experimental asthma in mice, suggesting that IL-37 may be critical
      for asthma pathogenesis in particular and may have an impact on adaptive immunity
      in general. Furthermore, these data suggest a mode of action of IL-37 that
      involves binding to IL-18Ralpha and subsequent heterodimerization with or
      activation of SIGIRR/IL-1R8. Therefore, IL-37 or its receptors could be potential
      targets for asthma intervention.

PMID- 27027964
TI  - Sputum Gene Expression of IL-13 Receptor alpha2 Chain Correlates with Airflow
      Obstruction and Helper T-Cell Type 2 Inflammation in Asthma.
AB  - BACKGROUND: BRP-39/YKL-40 is a chitinase-like protein that plays a critical role
      in IL-13-induced inflammation. It correlates positively with asthma severity and
      airway remodeling ( 1 ) via binding to IL-13 receptor alpha2 chain (IL
      13Ralpha2). Because the relationship of IL-13Ralpha2 to human asthma has never
      been evaluated previously, we sought to determine the relationship between IL
      13Ralpha2, YKL-40, and asthma. METHODS: We evaluated 112 patients (69% women)
      with a mean age of 46.7 years. Subjects completed an asthma phenotyping protocol
      that included analysis of sputum gene expression by Affymetrix 1.0 ST gene array
      (Affymetrix, Santa Clara, CA) and YKL-40 protein levels. MEASUREMENTS AND MAIN
      RESULTS: IL-13Ralpha2 gene expression was readily detectable in the sputum and
      correlated negatively with prebronchodilator (BD) FEV1 (rs = -0.282, P < 0.01),
      post-BD FEV1 (rs = -0.268, P < 0.01), pre-BD FEV1/FVC ratio (rs = -0.228, P <
      0.05), and post-BD FEV1/FVC ratio (rs = -0.242, P < 0.01). IL-13Ralpha2 gene
      expression correlated positively with gene expression of IL-13 (rs = 0.484, P <
      0.001), IL-5 (rs = 0.237, P < 0.05), and IL-8 (rs = 0.218, P < 0.05). Regression
      analysis showed that the post-BD FEV1/FVC ratio is significantly associated with
      IL-13Ralpha2 expression and CHI3L1 expression in sputum after controlling for IL
      4, IL-5, IL-13, and transforming growth factor-beta1 gene expression (all P <
      0.01). Sputum YKL-40 gene expression positively correlated with IL-8 expression
      (rs = 0.357, P < 0.001) and negatively correlated with pre- and post-BD FEV1/FVC
      ratios (rs = -0.299, P < 0.001 and rs = -0.305, P < 0.01, respectively). Sputum
      and serum YKL-40 protein levels were not associated with IL-13Ralpha2 expression.
      CONCLUSIONS: This analysis demonstrates that IL-13Ralpha2 is associated with
      reduced lung function, helper T-cell type 2 gene expression, and airflow
      obstruction in the airway of individuals with asthma, which might in turn be
      driven by airway remodeling. Future studies will be required to define the
      proinflammatory and remodeling effects of this receptor that up to now has been
      considered solely a modulator of IL-13-induced inflammation.

PMID- 27027965
TI  - Ablation of the Thiol Transferase Glutaredoxin-1 Augments Protein S
      Glutathionylation and Modulates Type 2 Inflammatory Responses and IL-17 in a
      House Dust Mite Model of Allergic Airway Disease in Mice.
AB  - S-glutathionylation has emerged as an oxidant-induced post-translational
      modification of protein cysteines that affects structure and function. The
      oxidoreductase glutaredoxin-1 (Glrx1), under physiological conditions, catalyzes
      deglutathionylation and restores the protein thiol group. The involvement of
      Grx1/S-glutathionylation in allergic inflammation induced by asthma-relevant
      allergens remains unknown. In the present study we examined the impact of genetic
      ablation of Glrx1 for the pathogenesis of house dust mite (HDM)-induced allergic
      airway disease in mice. Wild-type (WT) or Glrx1(-/-) mice in the BALB/c
      background were instilled intranasally with 50 MUg of HDM 5 consecutive days for
      3 weeks and killed 72 hours post final exposure. As expected, overall protein S
      glutathionylation was increased in Glrx1(-/-) mice exposed to HDM as compared
      with WT animals. Total cells in the bronchoalveolar lavage fluid were similarly
      increased in WT and Glrx1(-/-) HDM-treated mice compared with phosphate-buffered
      saline-treated control mice. However, in response to HDM, mice lacking Glrx1
      demonstrated significantly more neutrophils but fewer eosinophils than HDM
      exposed WT mice. mRNA expression of the Th2-associated cytokine IL-13, as well as
      MUC5ac, was significantly attenuated in Glrx1(-/-) HDM-treated mice compared with
      WT mice. Conversely, expression of IL-17A was increased in Glrx1(-/-) HDM mice
      compared with WT mice. Last, HDM-induced tissue damping and elastance were
      significantly attenuated in Glrx1(-/-) mice compared with WT littermates. These
      results demonstrate that the Grx1/S-glutathionylation redox status plays a
      pivotal role in HDM-induced allergic inflammation and airway hyperresponsiveness
      and suggest a potential role of Glrx1/S-glutathionylation in controlling the
      nature of the HDM-induced adaptive immune responses by promoting Type-2-driven
      inflammation and restricting IL-17A. 

PMID- 27027966
TI  - Vitamin D Reduces Inflammation-induced Contractility and Remodeling of Asthmatic
      Human Airway Smooth Muscle.
AB  - BACKGROUND: Although multiple clinical studies have found an association between
      vitamin D (Vit D) deficiency and asthma, a recent clinical study suggested lack
      of therapeutic effect of Vit D supplementation. Nonetheless, the mechanisms by
      which Vit D influences airway structure and function in the context of
      inflammation and asthma remains undefined. In this regard, Vit D effects on
      airway smooth muscle (ASM) are important, given the role of this cell type in the
      hypercontractility and remodeling. We assessed the mechanisms by which Vit D
      modulates the enhancing effects of proinflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha) and IL-13 on intracellular Ca(2+) ([Ca(2+)]i) levels and
      remodeling in nonasthmatic versus asthmatic human ASM. METHODS: Human ASM was
      enzymatically isolated from surgical lung specimens of patients with clinically
      defined mild to moderate asthma versus no asthma. Cells were treated with 10
      ng/ml TNF-alpha and 50 ng/ml IL-13 in the presence or absence of 100 nM
      calcitriol. MEASUREMENTS AND MAIN RESULTS: Interestingly, Vit D receptor (VDR)
      and retinoic X receptor-alpha levels were maintained, even increased, in subjects
      with asthma when treated with TNF-alpha and IL-13. Compared with untreated cells,
      calcitriol blunted the heightened effect of TNF-alpha on [Ca(2+)]i response to
      histamine in ASM. Calcitriol particularly blunted TNF-alpha and IL-13 effects on
      collagen and fibronectin deposition, especially in asthmatic ASM. Calcitriol
      stimulated VDR/retinoic X receptor dimerization and VDR activity even in subjects
      with asthma and with IL-13, highlighting retained functionality. Expression of
      Class I histone deacetylases 1-3 (HDAC) and overall HDAC activity were lower in
      IL-13-exposed ASM, but calcitriol enhanced HDAC expression/activity. CONCLUSIONS:
      In asthmatic ASM, Vit D functionality is maintained, allowing calcitriol to
      reduce the procontractile and proremodeling effects of inflammatory cytokines,
      particularly IL-13, which is relevant to asthma. These findings highlight a
      potential role for Vit D in asthma pathogenesis, particularly in the context of
      airway structure and functional changes early in disease.

PMID- 27027967
TI  - Mucins and Their Sugars. Critical Mediators of Hyperreactivity and Inflammation.
AB  - Excessive mucus causes severe airflow obstruction in fatal asthma. It is also
      present in mild to moderate disease, but is poorly understood and treated. Mucus
      overproduction is associated with dysregulated expression of the mucins MUC5AC
      and MUC5B. Whereas increased MUC5AC is a consistent finding, MUC5B varies
      remaining stably produced in some patients but strongly repressed in others
      (>90%). Patients with lower MUC5B display worsened asthma phenotypes including
      airway hyperreactivity (AHR) to methacholine (MCh) and eosinophilic inflammation.
      To better understand the roles of mucins in asthma, we generated Muc5ac and Muc5b
      knockout ((-/-)) mice. AHR to MCh was abolished in antigen-challenged Muc5ac(-/-)
      mice, due to prevention of heterogeneous mucous plugging that occurred in
      allergic wild-type mice during MCh-induced bronchoconstriction. Thus, in addition
      to the established role of smooth muscle-mediated airway narrowing, Muc5ac is an
      essential noncontractile AHR component. We also found that, unlike Muc5ac(-/-)
      mice, Muc5b-deficient mice were not protected from asthma phenotypes.
      Furthermore, whereas inflammation was unaffected by Muc5ac deficiency, it was
      exaggerated in the absence of Muc5b. On the basis of these differential effects,
      we are now determining how asthma phenotypes are regulated by mucin isoform
      specificity. Glycosylation is dramatically different: Muc5ac is heavily
      fucosylated whereas Muc5b is mainly sialylated. Fucosylation increases mucus
      viscoelasticity, and FUT2, the enzyme that catalyzes mucin alpha1,2-fucosylation,
      is associated with severe asthma exacerbation risk. Sialylation is required for
      binding to siglec (sialic acid-binding immunoglobulin-like lectin) receptors on
      leukocytes. Eosinophils express Siglec-F (mouse) or Siglec-8 (human). Engagement
      by sialoside ligands induces eosinophil apoptosis, and Muc5b via sialylated
      termini that require the alpha2,3-sialyltransferase ST3Gal3 for synthesis binds
      Siglec-F and induces apoptosis in mouse eosinophils. Because Muc5b is required
      for host defense in mouse lungs, inhibiting MUC5AC while preserving or enhancing
      MUC5B functions may be effective for treating asthma. 

PMID- 27027968
TI  - Identifying Molecular Mechanisms of the Late-Phase Asthmatic Response by
      Integrating Cellular, Gene, and Metabolite Levels in Blood.
AB  - RATIONALE: Individuals with allergic asthma respond differently, but
      reproducibly, to allergen inhalation challenge. Some individuals develop an
      isolated early response (early responders) (ERs), whereas others go on to develop
      a late response (dual responders) (DRs). It is not understood why late responses
      do not develop in all sensitized individuals. OBJECTIVES: The aim of this study
      was to identify blood biomarkers that can discriminate ERs and DRs using cellular
      frequencies and gene and metabolite expression from whole blood. METHODS: Thirty
      two individuals participated in the allergen inhalation challenge as part of the
      AllerGen Clinical Investigator Collaborative. Fifteen participants were
      classified as ERs and 17 as DRs. Blood samples were collected before (pre) and 2
      hours after (post) the allergen challenge. Cell counts were obtained using a
      hematolyzer, gene transcript relative levels using RNA sequencing, and metabolite
      concentrations using tandem mass spectrometry. An integrative ensemble algorithm
      that was based on canonical correlation analysis was used to classify ERs and DRs
      using all three data sets, adjusting for age and sex. The objective of this
      algorithm was to identify a correlated subset of molecules from each data set
      that best discriminated ERs from DRs. Gene set enrichment analysis was performed
      using Enrichr (Chen et al., BMC Bioinformatics 2013;128). MEASUREMENTS AND MAIN
      RESULTS: The pre-challenge multisignature classifier (error = 30%) outperformed
      the post-challenge multisignature classifier (error = 50%) in separating ERs from
      DRs. The cells selected in the prechallenge multisignature panel included
      eosinophils, lymphocytes, and neutrophils. The selected metabolites were enriched
      for glycerophospholipids. The subset of gene transcripts in the multisignature
      panel was enriched for the T-cell receptor and costimulatory signaling pathway (P
      = 3.4 * 10(-6)) (Wikipathways) and positive regulation of antigen receptor
      mediated signaling pathway (P = 5.7 * 10(-4)) (GO Ontology). CONCLUSIONS: This
      study provides a systems perspective on the deregulated molecular processes
      between early and dual responses in whole blood. The integrative biomarker
      analysis suggests that a molecular signature that is predictive of the late-phase
      response can be identified. The variability in the onset of the late response may
      explain the poor predictive performance of the postchallenge multiomic biomarker
      signature. Replication of the prechallenge biomarker signature in additional
      independent samples is required to validate this panel.

PMID- 27027969
TI  - Amish and Hutterite Environmental Farm Products Have Opposite Effects on
      Experimental Models of Asthma.

PMID- 27027970
TI  - DNA Methylation Changes in Nasal Epithelia Are Associated with Allergic Asthma in
      the Inner City.

PMID- 27027971
TI  - Risk assessment of soils identified on firefighter turnout gear.
AB  - The purpose of this research was to identify the composition of soils on
      firefighter turnout gear and to determine the dermal exposure risks associated
      with the soils. Nine used Nomex hoods from the Philadelphia fire department were
      analyzed for the presence of trace metals and seven sets of used turnout gear
      were analyzed for semi-volatile organics. Turnout gear samples were removed from
      areas of the gear known to have high levels of dermal absorption including the
      collar, armpit, wrist, and crotch areas, from either the outer shell or thermal
      liner layers. The following compounds were detected: polycyclic aromatic
      hydrocarbons (PAHs), phthalate plasticizers, and polybrominated diphenyl ether
      flame retardants (PBDEs). A screening risk assessment was conducted by converting
      the measured concentrations to an estimated dermally absorbed dose based on
      estimates for the permeation coefficient (Kp) and an assumed firefighting
      exposure scenario. Benzo(a) pyrene had the highest dermal exposure risk based on
      carcinogenic effects and PBDE-99 had the highest dermal exposure risk based on
      non-carcinogenic effects. For the metals, arsenic had the highest dermal exposure
      risk for the use hoods.

PMID- 27027972
TI  - Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk
      worth considering antifungal prophylaxis?
AB  - The aim of this study is to analyse the risk of invasive fungal infection (IFI)
      and the need for antifungal prophylaxis in patients with acute myeloid leukaemia
      and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We
      retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in
      121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5,
      range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one
      probable aspergillosis and one proven candidemia) occurred in this series. The
      incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per
      patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per
      patient treated in those with severe neutropenia. Two patients died from IFI,
      leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per
      treatment cycle. The numbers needed to treat with prophylaxis to prevent one case
      of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment
      course, and 137 azacitidine cycles or 24 patients among those with severe
      neutropenia. AML/MDS patients treated with azacitidine, including those with
      severe prolonged neutropenia, have a very low risk of IFI which does not justify
      the use of antifungal prophylaxis. 

PMID- 27027973
TI  - Tic-Tac-Toe Binary Lattices from the Interfacial Self-Assembly of Branched and
      Spherical Nanocrystals.
AB  - The self-organization of nanocrystals has proven to be a versatile route to
      achieve increasingly sophisticated structures of materials, where the shape and
      properties of individual particles impact the final functionalities. Recent works
      have addressed this topic by combining various shapes to achieve more complex
      arrangements of particles than are possible in single-component samples. However,
      the ability to create intricate architectures over large regions by exploiting
      the shape of multiply branched nanocrystals to host a second component remains
      unexplored. Here, we show how the concave shape of a branched nanocrystal, the so
      called octapod, is able to anchor a sphere. The two components self-assemble into
      a locally ordered monolayer consisting of an intercalated square lattice of
      octapods and spheres, which is reminiscent of the "tic-tac-toe" game. These tic
      tac-toe domains form through an interfacial self-assembly that occurs by the
      dewetting of a hexane layer containing both particle types. By varying the
      experimental conditions and performing molecular dynamics simulations, we show
      that the ligands coating the octapods are crucial to the formation of this
      structure. We find that the tendency of an octapod to form an interlocking-type
      structure with a second octapod strongly depends on the ligand shell of the pods.
      Breaking this tendency by ligand exchange allows the octapods to assemble into a
      more relaxed configuration, which is able to form a lock-and-key-type structure
      with a sphere, when they have a suitable size ratio. Our findings provide an
      example of a more versatile use of branched nanocrystals in self-assembled
      functional materials.

PMID- 27027974
TI  - REM sleep behavior disorder and periodic leg movements during sleep in ALS.
AB  - OBJECTIVE: To assess sleep characteristics and the occurrence of abnormal muscle
      activity during sleep, such as REM sleep without atonia (RSWA), REM sleep
      behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in
      patients with amyotrophic lateral sclerosis (ALS). METHODS: A total of 41
      patients with ALS and 26 healthy subjects were submitted to clinical interview
      and overnight video-polysomnography. RESULTS: A total of 22 patients with ALS
      (53.6%) reported poor sleep quality. Polysomnographic studies showed that
      patients with ALS had reduced total sleep time, increased wakefulness after sleep
      onset, shortened REM and slow-wave sleep, and decreased sleep efficiency,
      compared to controls. Polysomnographic abnormalities were not different in
      patients reporting good or poor sleep and were not correlated to clinical and
      demographic variables. The PLMS index was significantly higher in patients with
      ALS than in healthy subjects, and 22 patients (53.6%) showed a PLMS index > 15/h,
      vs 4 (15.4%) controls (P < 0.001). Finally, two patients with ALS (4.9%) had RBD,
      and two more patients presented RSWA (4.9%), whereas no controls showed
      abnormalities of REM sleep. CONCLUSION: Patients with ALS frequently present
      abnormalities of sleep that can be documented both at the clinical interview and
      at the polysomnographic evaluation, including insomnia, fragmented sleep, and
      increased PLMS. Moreover, abnormalities of REM sleep can be found in some of
      these patients.

PMID- 27027975
TI  - Cost-effective imprinting combining macromolecular crowding and a dummy template
      for the fast purification of punicalagin from pomegranate husk extract.
AB  - The combination of molecular crowding and virtual imprinting was employed to
      develop a cost-effective method to prepare molecularly imprinted polymers. By
      using linear polymer polystyrene as a macromolecular crowding agent, an imprinted
      polymer recognizable to punicalagin had been successfully synthesized with
      punicalin as the dummy template. The resulting punicalin-imprinted polymer
      presented a remarkable selectivity to punicalagin with an imprinting factor of
      3.17 even at extremely low consumption of the template (template/monomer ratio of
      1:782). In contrast, the imprinted polymer synthesized without crowding agent,
      did not show any imprinting effect at so low template amount. The imprinted
      polymers made by combination of molecular crowding and virtual imprinting can be
      utilized for the fast separation of punicalagin from pomegranate husk extract
      after optimizing the protocol of solid-phase extraction with the recovery of 85.3
      +/- 1.2%. 

PMID- 27027976
TI  - Biotechnology and Translational Medicine.

PMID- 27027977
TI  - Erratum: Adipose tissue fatty acid chain length and mono-unsaturation increases
      with obesity and insulin resistance.

PMID- 27027978
TI  - Response to transarterial chemoembolization as a selection criterion for
      resection of hepatocellular carcinomas.
AB  - BACKGROUND: Liver resection for intermediate (Barcelona Clinic Liver Cancer
      (BCLC) stage B) hepatocellular carcinoma (HCC) remains controversial. This study
      attempted to demonstrate the effectiveness of preresection transarterial
      chemoembolization (TACE) as a selection criterion for BCLC-B HCC. METHODS: The
      study included patients with BCLC-B HCC who underwent liver resection after TACE.
      The tumour response to TACE was evaluated according to the modified Response
      Evaluation Criteria in Solid Tumours (mRECIST). Patients with a complete or
      partial response comprised the responder group, whereas those with stable or
      progressive disease were classified as non-responders. RESULTS: A total of 242
      patients were included. After between one and eight sessions of TACE, 141
      patients were included in the responder group: 37 patients (15.3 per cent) who
      achieved a complete response and 104 who had a partial response. The cumulative 1
      , 3- and 5-year overall survival rates were 97.2, 88.7 and 75.2 per cent
      respectively in the responder group, compared with 90.1, 67.3 and 53.5 per cent
      among 101 non-responders (P < 0.001). Tumour-free survival rates were also better
      among responders than non-responders (P < 0.001). In multivariable analysis,
      independent predictors of overall and tumour-free survival were response to TACE
      and microvascular invasion (all P < 0.001). CONCLUSION: mRECIST may represent
      selection criterion for intermediate HCC for surgical treatment.

PMID- 27027979
TI  - Guest-Induced Arylamide Polymer Helicity: Twist-Sense Bias and Solvent-Dependent
      Helicity Inversion.
AB  - A benzene/naphthalene alternately incorporated amide polymer was synthesized and
      characterized. (1) H NMR spectroscopy, fluorescence, and circular dichroism (CD)
      experiments indicated that, in chloroform, the polymer could be induced by the
      chiral l-aspartic acid dianion or one of its derivatives to form a helical
      tubular conformation with twist-sense bias. CD titration studies showed that the
      l-aspartic acid dianion (8 equiv.) could lead to a maximum Cotton effect. It was
      also revealed that the twist-sense bias obeyed the majority rule, and 70 %
      enantiomeric excess could realize the maximum helicity bias. Adding acetonitrile
      to the solution of chloroform caused inversion of the guest-induced helicity bias
      of the polymer.

PMID- 27027980
TI  - Congenital limb deficiency classification and nomenclature: The need for a
      consensus.
AB  - After the thalidomide epidemic in the early 1960s, many jurisdictions developed
      congenital anomaly surveillance systems. Congenital limb deficiencies can act as
      indicators of potential teratogens. The classification of congenital limb
      deficiencies is essential to determine the precise cause or causes of this
      anomaly. This article describes the different terminology and classification that
      have been used over time and the need for a consensus. While there are a variety
      of studies examining the epidemiology and etiology of congenital limb
      deficiencies, there is an inconsistent use of terminology and classification
      which makes comparisons between studies challenging. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27027981
TI  - Functional Arrays for Light Energy Capture and Charge Separation.
AB  - This article draws, with a simplified but rigorous approach, the typical
      procedure for the design and optimization of functional multicomponent structures
      for light to chemical energy conversion for two series of multipartite structures
      based on prototypical chromophores: polypyridyl metal complexes and
      porphyrinoids. Starting from a photophysical study performed by steady-state and
      time-resolved spectroscopic methods, the full deactivation dynamics of the light
      absorbing chromophore(s) are disclosed. The preferred deactivation step (electron
      transfer in this case) is then optimized. This can be done by simply operating on
      the solvent, but also by changing structure/components that can alter electronic
      and nuclear factors, via continuous feedback with the research groups in charge
      of the synthesis. With a presentation suitable for a wide audience, it is here
      discussed how the effective design of functional multicomponent structures for
      charge separation can be achieved.

PMID- 27027982
TI  - Prognostic Impact of Implementation of QRS Characteristics in the Seattle Heart
      Failure Model in ICD and CRT-D Recipients.
AB  - BACKGROUND: The Seattle Heart Failure Model (SHFM) provides accurate estimates of
      survival in heart failure (HF) patients. The model is, however, not developed for
      HF patients with cardiac resynchronization therapy (CRT). The aim of this study
      was to assess the prognostic value of SHFM combined with QRS morphology and CRT
      related change in QRS duration in implantable cardioverter defibrillator (ICD)
      and CRT defibrillator (CRT-D) recipients. METHODS: All patients who underwent
      prophylactic ICD implantation at the Leiden University Medical Center since 1996
      were included. Baseline SHFM, QRS morphology, and duration before and after
      device implantation were determined. The regression coefficients of the QRS
      characteristics derived from a Cox regression analysis were implemented in the
      SHFM. SHFM-estimated survival was compared with Kaplan-Meier observed survival.
      RESULTS: The current study includes 1,834 defibrillator recipients (63 +/- 11
      years; 79% male; 53% CRT-D). In 585 (60%) CRT-D recipients a left bundle branch
      block was present, the mean QRS duration was 147 +/- 31 ms before and 151 +/- 27
      ms after device implantation. After a median follow-up of 4.4 years (25(th) 
      75(th) percentile 2.7-6.4 years), 285 (29%) CRT-D recipients had died. CRT
      related decrease in QRS duration adjusted for QRS morphology was associated with
      improved survival (hazard ratio 1.05/10 ms; 95% confidence interval [CI]: 1.01
      1.09; P = 0.02). The estimated 5-year survival of CRT-D recipients after
      implementation of the QRS characteristic was 70%, and comparable with the
      observed 5-year survival of 68% (95% CI: 65-72). CONCLUSION: Implementation of
      native QRS morphology and change in QRS duration due to CRT in the SHFM improves
      the prognostic value of this model in HF patients with CRT-D.

PMID- 27027984
TI  - Scripting MODFLOW Model Development Using Python and FloPy.
AB  - Graphical user interfaces (GUIs) are commonly used to construct and postprocess
      numerical groundwater flow and transport models. Scripting model development with
      the programming language Python is presented here as an alternative approach. One
      advantage of Python is that there are many packages available to facilitate the
      model development process, including packages for plotting, array manipulation,
      optimization, and data analysis. For MODFLOW-based models, the FloPy package was
      developed by the authors to construct model input files, run the model, and read
      and plot simulation results. Use of Python with the available scientific packages
      and FloPy facilitates data exploration, alternative model evaluations, and model
      analyses that can be difficult to perform with GUIs. Furthermore, Python scripts
      are a complete, transparent, and repeatable record of the modeling process. The
      approach is introduced with a simple FloPy example to create and postprocess a
      MODFLOW model. A more complicated capture-fraction analysis with a real-world
      model is presented to demonstrate the types of analyses that can be performed
      using Python and FloPy.

PMID- 27027985
TI  - Multidetector computed tomography features of pancreatic metastases from
      leiomyosarcoma: Experience at a tertiary cancer center.
AB  - AIM: To describe the multidetector computed tomography features of pancreatic
      metastasis from leiomyosarcoma (LMS). METHODS: Between January 1995 and December
      2012, 13 consecutive patients (11 women, 2 men; mean age of 57 years; range, 38
      78 years) with pancreatic metastases from LMS were included in our study. Imaging
      features including location, number, largest dimension, tumor attenuation and
      enhancement characteristics, presence of necrosis, pancreatic ductal dilatation,
      common bile duct (CBD) dilatation, presence of pancreatitis, and atrophy were
      documented. RESULTS: The most common site of origin of the pancreatic metastases
      from LMS was uterus (38.5%), followed by retroperitoneum (30.8%) and extremity
      (23.1%). None of the patients in our study had pancreas as the first site of
      metastasis. All patients developed pancreatic metastases at a median interval of
      24 mo. Pancreatic metastases from LMS were solitary in 8/13 patients and multiple
      in 5/13 patients, had no predilection for any part of the pancreas, were
      hypovascular on arterial phase in 10/13 patients and associated with pancreatic
      duct dilatation in 3/13 patients. None had CBD dilatation. None of the pancreatic
      metastases in LMS cohort caused pancreatitis, and atrophy. Median duration of
      follow-up was 19 mo for LMS cohort during which two patients underwent resection
      of metastasis (median survival 45 mo) while the remaining underwent systemic
      therapy (median survival 13 mo). CONCLUSION: Pancreatic metastases from LMS are
      often solitary and hypovascular masses and less commonly associated with
      pancreatic ductal dilatation, CBD dilatation, pancreatitis or pancreatic atrophy.
      Surgical resection of solitary LMS pancreatic metastasis can be considered due to
      the long survival of these patients.

PMID- 27027986
TI  - Current-use pesticides in seawater and their bioaccumulation in polar bear-ringed
      seal food chains of the Canadian Arctic.
AB  - The distribution of current-use pesticides (CUPs) in seawater and their
      trophodynamics were investigated in 3 Canadian Arctic marine food chains. The
      greatest ranges of dissolved-phase concentrations in seawater for each CUP were
      endosulfan sulfate (less than method detection limit (MDL) to 19 pg L(-1) ) >
      dacthal (0.76-15 pg L(-1) ) > chlorpyrifos (less than MDL to 8.1 pg L(-1) ) >
      pentachloronitrobenzene (less than MDL to 2.6 pg L(-1) ) > alpha-endosulfan (0.20
      2.3 pg L(-1) ). Bioaccumulation factors (BAFs, water-respiring organisms) were
      greatest in plankton, including chlorothalonil (log BAF = 7.4 +/- 7.1 L kg(-1) ,
      mean +/- standard error), chlorpyrifos (log BAF = 6.9 +/- 6.7 L kg(-1) ), and
      alpha-endosulfan (log BAF = 6.5 +/- 6.0 L kg(-1) ). The largest biomagnification
      factors (BMFs) were found for dacthal in the capelin:plankton trophic
      relationship (BMF = 13 +/- 5.0) at Cumberland Sound (Nunvavut), and for beta
      endosulfan (BMF = 16 +/- 4.9) and alpha-endosulfan (BMF = 9.3 +/- 2.8) in the
      polar bear-ringed seal relationship at Barrow and Rae Strait (NU), respectively.
      Concentrations of endosulfan sulfate exhibited trophic magnification (increasing
      concentrations with increasing trophic level) in the poikilothermic portion of
      the food web (trophic magnification factor = 1.4), but all of the CUPs underwent
      trophic dilution in the marine mammal food web, despite some trophic level
      specific biomagnification. Together, these observations are most likely
      indicative of metabolism of these CUPs in mammals. Environ Toxicol Chem
      2016;35:1695-1707. (c) 2016 SETAC.

PMID- 27027988
TI  - Sleep duration estimates of Canadian children and adolescents.
AB  - The objective of this study was to provide contemporary sleep duration estimates
      of Canadian school-aged children and adolescents and to determine the proportion
      adhering to the sleep duration recommendations. This study included 24 896
      participants aged 10-17 years from the 2013/2014 Canadian Health Behaviour in
      School-aged Children study (HBSC), a nationally representative cross-sectional
      study. Bedtime and wake-up times were reported by participants and their sleep
      duration was calculated. Participants were then classified as having a sleep
      duration that met the recommended range (9-11 h per night for 10-13-year-olds or
      8-10 h per night for 14-17-year-olds), a sleep duration that was shorter than the
      recommended range or a sleep duration that was longer than the recommended range.
      An estimated 68% of children aged 10-13 years and 72% of adolescents aged 14-17
      years sleep for the recommended amount per night when averaged across all days of
      the week. Short sleepers represent 31% of school-aged children and 26% of
      adolescents. Long sleepers are rare (<2% overall). Children and adolescents sleep
      ~1 h more at weekends compared to weekdays. Approximately 5% of the participants
      typically went to bed after midnight on weekdays and 31% did so at weekends;
      these proportions reached 11 and 45%, respectively, within 16-17-year-olds. In
      general, differences in sleep times between boys and girls are small and not
      clinically significant. In conclusion, almost one-third of Canadian children and
      adolescents sleep less than the recommended amount. Public health efforts should
      continue to monitor the sleep of Canadian children and adolescents and identify
      subgroups of the population more likely to be affected by insufficient sleep.

PMID- 27027987
TI  - Increased hepatic progenitor cell response and ductular reaction in patients with
      severe recurrent HCV post-liver transplantation.
AB  - OBJECTIVES: Post-liver transplant (LT) hepatitis C virus (HCV) patients may
      develop allograft cirrhosis and rarely fibrosing cholestatic hepatitis (FCH),
      while others have a stable course. Hepatic progenitor cells (HPC) may be
      implicated in liver injury and fibrogenesis through ductular reaction (DR). We
      studied HPC response and DR in three distinct post-LT patterns of HCV: stable
      recurrence, allograft cirrhosis, and FCH. METHODS: We identified 52 patients with
      untreated recurrent HCV and longitudinal liver biopsies (20 stable/23 cirrhosis/9
      FCH) and eight healthy controls. Archived liver biopsy specimens for three time
      points (LT; initial recurrence; and clinical outcome) were stained for
      cytokeratin-7. Manual HPC counts and DR quantification using image analysis were
      performed. RESULTS: HCV counts and DR at LT did not differ across groups. At
      initial recurrence, HPC expansion occurred only in patients who developed
      cirrhosis, while prominent DR was present in those who developed FCH vs. stable
      and controls (p < 0.05). At outcome biopsies, HPC response and DR were increased
      in cirrhosis and FCH vs. stable and controls (p < 0.05). HPC response and DR did
      not differ in stable vs. CONCLUSIONS: These findings suggest that an altered HPC
      response assessed by cytokeratin-7 stain after LT may predict severity of HCV
      recurrence.

PMID- 27027989
TI  - The prevalence of complex multimorbidity in Australia.
AB  - OBJECTIVE: To measure prevalence of multimorbidity and complex multimorbidity in
      the Australian population from a nationally representative prospective study and
      to identify the most prevalent patterns of chronic conditions and body systems
      affected. METHODS: A sub-study of the nationally representative BEACH program,
      using a random sample of 8,707 patients at encounters with 290 general
      practitioners. All diagnosed chronic conditions were recorded for each patient.
      Multimorbidity was defined as co-occurrence of 2+ chronic conditions, while
      complex multimorbidity was defined as 3+ body systems each affected by at least
      one chronic condition. RESULTS: We estimated: 47.4% of patients at GP encounters
      and one-third (32.6%) of the population had multimorbidity; and 27.4% of patients
      at GP encounters and 17.0% of the Australian population had complex
      multimorbidity. The most prevalent combination pattern of three conditions was
      hypertension+hyperlipidaemia+ osteoarthritis (5.5% of patient at encounters and
      3.3% of the population). Most prevalent combination of three body systems
      affected was circulatory+musculoskeletal+endocrine / nutritional/metabolic
      systems (11.1% of patients at encounters and 7.0% of the population). CONCLUSIONS
      AND IMPLICATIONS: A significant proportion of Australians have not only
      multimorbidity, but complex multimorbidity. To meet the challenge posed by
      complex multimorbidity, the single disease focus of our healthcare system needs
      to be re-evaluated.

PMID- 27027990
TI  - Effects of the 2010 Haiti Earthquake on Women's Reproductive Health.
AB  - This article explores the effects of the 2010 Haiti earthquake on women's
      reproductive health, using geocoded data from the 2005 and 2012 Haiti Demographic
      and Health Surveys. We use geographic variation in the destructiveness of the
      earthquake to conduct a difference-in-difference analysis. Results indicate that
      heightened earthquake intensity reduced use of injectables-the most widely used
      modern contraceptive method in Haiti-and increased current pregnancy and current
      unwanted pregnancy. Analysis of impact pathways suggests that severe earthquake
      intensity significantly increased women's unmet need for family planning and
      reduced their access to condoms. The earthquake also affected other factors that
      influence reproductive health, including women's ability to negotiate condom use
      in their partnerships. Our findings highlight how disruptions to health care
      services following a natural disaster can have negative consequences for women's
      reproductive health. 

PMID- 27027991
TI  - Instability in Parent-Child Coresidence and Adolescent Development in Urban South
      Africa.
AB  - There is widespread recognition of the importance of family stability for child
      development. South Africa presents an interesting context in which to study the
      consequences of family instability because of the traditionally fluid nature of
      household composition due to labor migration, child fostering, and non-marital
      fertility. More recently, the HIV pandemic has added another source of
      instability. Within South Africa, however, patterns of instability differ
      markedly across racial groups. We use the Cape Area Panel Study (CAPS) data to
      examine the implications of changes in parent-child coresidence for educational
      and sexual development of young South Africans. We show that changes in maternal
      and paternal coresidence have implications for the timing of sexual initiation
      for both black and coloured adolescents. Maternal and paternal transitions also
      lead to poorer educational outcomes for coloured adolescents, but parental
      disruptions are not significantly related to educational outcomes for blacks.
      These findings suggest that the implications of coresidential instability vary by
      race, reflecting racial differences with respect to cultural, social, and
      economic conditions. 

PMID- 27027993
TI  - Emergency Contraception in Post-Conflict Somalia: An Assessment of Awareness and
      Perceptions of Need.
AB  - In conflict-affected settings such as Somalia, emergency contraception (EC) has
      the potential to serve as an important means of pregnancy prevention. Yet Somalia
      remains one of the few countries without a registered progestin-only EC pill. In
      2014, we conducted a qualitative, multi-methods study in Mogadishu to explore
      awareness of and perceptions of need for EC. Our project included 10 semi
      structured key informant interviews, 20 structured in-person interviews with
      pharmacists, and four focus group discussions with married and unmarried Somali
      women. Our findings reveal a widespread lack of knowledge of both existing family
      planning methods and EC. However, once we described EC, participants expressed
      enthusiasm for expanding access to post-coital contraception. Our results shed
      light on why Somalia continues to be a global exception with respect to an EC
      product and suggest possible politically and culturally acceptable and effective
      avenues for introducing EC into the health system. 

PMID- 27027992
TI  - Respondents' Exposure to Community-based Services and Reported Fertility
      Regulation Behavior: A Decade of Data from the Navrongo Community Health and
      Family Planning Project.
AB  - This article examines a decade of demographic surveillance data from rural
      northern Ghana linked with prospective panel survey data recording respondents'
      reported fertility-regulation behavior. We assess the impact of access to
      community-based contraceptive services, reported fertility-regulation behavior,
      and their interaction on the risk of a conception that results in a birth. The
      effects of service exposure differ by marital status. Reported use of any method
      to delay or avoid pregnancy appears to be more effective in reducing the risk of
      conception among the unmarried in areas offering community-based contraceptive
      services, relative to those in areas where services are facility based. Among
      both married and unmarried survey respondents who state that they are not using
      contraception, the risk of conception is lower among women in areas with
      community-based services than among women in communities without these services.
      The lower risk of conception among women who are receiving community-based
      services and who report that they are regulating their fertility may be due to
      increased efficacy and duration of fertility regulation. Among women who report
      that they are not regulating their fertility, under-reporting of contraceptive
      use in experimental areas is likely to play a role in explaining these findings. 

PMID- 27027994
TI  - The End of China's One-Child Policy.
AB  - Starting on January 1, 2016, all Chinese couples are allowed to have two
      children. This marks the end of China's one-child policy, which has restricted
      the majority of Chinese families to only one child for the last 35 years. Yet,
      China's policy change came at least a decade later than it should have. The
      costly lessons to be learned are not only in politics and public policymaking,
      but also in how parts of the academic community informed and misinformed public
      policymaking. 

PMID- 27027995
TI  - Egypt 2014.

PMID- 27027996
TI  - Zambia 2013-14.

PMID- 27027997
TI  - PH-domains as central modulators driving tumor growth.

PMID- 27027998
TI  - The WEE1 regulators CPEB1 and miR-15b switch from inhibitor to activators at
      G2/M.
AB  - MicroRNAs (miRNAs) in the AGO-containing RISC complex control messenger RNA
      (mRNA) translation by binding to mRNA 3' untranslated region (3'UTR). The
      relationship between miRNAs and other regulatory factors that also bind to mRNA
      3'UTR, such as CPEB1 (cytoplasmic polyadenylation element-binding protein),
      remains elusive. We found that both CPEB1 and miR-15b control the expression of
      WEE1, a key mammalian cell cycle regulator. Together, they repress WEE1 protein
      expression during G1 and S-phase. Interestingly, the 2 factors lose their
      inhibitory activity at the G2/M transition, at the time of the cell cycle when
      WEE1 expression is maximal, and, moreover, rather activate WEE1 translation in a
      synergistic manner. Our data show that translational regulation by RISC and CPEB1
      is essential in cell cycle control and, most importantly, is coordinated, and can
      be switched from inhibition to activation during the cell cycle. 

PMID- 27027999
TI  - MiRImpact, a new bioinformatic method using complete microRNA expression profiles
      to assess their overall influence on the activity of intracellular molecular
      pathways.
AB  - MicroRNAs (miRs) are short noncoding RNA molecules that regulate expression of
      target mRNAs. Many published sources provide information about miRs and their
      targets. However, bioinformatic tools elucidating higher level impact of the
      established total miR profiles, are still largely missing. Recently, we developed
      a method termed OncoFinder enabling quantification of the activities of
      intracellular molecular pathways basing on gene expression data. Here we propose
      a new technique, MiRImpact, which enables to link miR expression data with its
      estimated outcome on the regulation of molecular pathways, like signaling,
      metabolic, cytoskeleton rearrangement, and DNA repair pathways. MiRImpact uses
      OncoFinder rationale for pathway activity calculations, with the major
      distinctions that (i) it deals with the concentrations of miRs--known regulators
      of gene products participating in molecular pathways, and (ii) miRs are
      considered as negative regulators of target molecules, if other is not specified.
      MiRImpact operates with 2 types of databases: for molecular targets of miRs and
      for gene products participating in molecular pathways. We applied MiRImpact to
      compare regulation of human bladder cancer-specific signaling pathways at the
      levels of mRNA and miR expression. We took 2 most complete alternative databases
      of experimentally validated miR targets--miRTarBase and DianaTarBase, and an
      OncoFinder database featuring 2725 gene products and 271 signaling pathways. We
      showed that the impact of miRs is orthogonal to pathway regulation at the mRNA
      level, which stresses the importance of studying posttranscriptional regulation
      of gene expression. We also report characteristic set of miR and mRNA regulation
      features linked with bladder cancer.

PMID- 27028001
TI  - PyMIF enhances the inflammatory response in a rodent model by stimulating
      CD11b(+) Ly6C(+) cells accumulation in spleen.
AB  - Macrophage migration inhibitory factor (PMIF) expressed by Plasmodium parasites
      has been proved to be similar to the mammalian MIF in both structure and
      biological activity and is a critical upstream regulator in antimalaria innate
      immunity. In this work, using a genetically modified (MIF-KO) strain of highly
      lethal rodent Plasmodium yoelii 17XL (Py17XL), we found that PyMIF could increase
      the secretion of pro-inflammatory factors by eliciting the CD11b(+) Ly6C(+) cells
      accumulated in the spleen of infected mouse. In addition, the chemotactic effect
      of PyMIF was demonstrated to associate with cell receptors CXCR2, CXCR4 and the
      cell surface markers ICAM-1, LFA-4.

PMID- 27028000
TI  - Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing
      mice during the growth period.
AB  - Growth hormone (GH) is a pleiotropic hormone that triggers STATs, ERK1/2 and Akt
      signaling, related to cell growth and proliferation. Transgenic mice
      overexpressing GH present increased body size, with a disproportionate liver
      enlargement due to hypertrophy and hyperplasia of the hepatocytes. We had
      described enhanced mitogenic signaling in liver of young adult transgenic mice.
      We now evaluate the activation of these signaling cascades during the growth
      period and relate them to the morphological alterations found. Signaling
      mediators, cell cycle regulators and transcription factors involved in cellular
      growth in the liver of GH-overexpressing growing mice were assessed by
      immunoblotting, RT-qPCR and immunohistochemistry. Hepatocyte enlargement can be
      seen as early as 2-weeks of age in GH-overexpressing animals, although it is more
      pronounced in young adults. Levels of cell cycle mediators PCNA and cyclin D1,
      and transcription factor c-Jun increase with age in transgenic mice with no
      changes in normal mice, whereas c-Myc levels are higher in 2-week-old transgenic
      animals and cyclin E levels decline with age for both genotypes. STAT3, Akt and
      GSK3 present higher activation in the adult transgenic mice than in the growing
      animals, while for c-Src and mTOR, phosphorylation in GH-overexpressing mice is
      higher than in control siblings at 4 and 9 weeks of age. No significant changes
      are observed for ERK1/2, neither by age or genotype. Thus, the majority of the
      mitogenic signaling pathways are gradually up-regulated in the liver of GH
      transgenic mice, giving rise to the hepatic morphological changes these mice
      exhibit.

PMID- 27028002
TI  - Resistant dextrin, as a prebiotic, improves insulin resistance and inflammation
      in women with type 2 diabetes: a randomised controlled clinical trial.
AB  - Improvement of insulin resistance and inflammation is a basic strategy in the
      management of type 2 diabetes. There is limited evidence that prebiotics improve
      insulin resistance and inflammation. However, the ameliorating effect of
      resistant dextrin, as a prebiotic, on insulin resistance and inflammation in
      patients with type 2 diabetes has not been investigated so far. Therefore, the
      present study aimed to examine the effects of resistant dextrin on insulin
      resistance and inflammation in type 2 diabetic patients. In a randomised
      controlled clinical trial, fifty-five women with type 2 diabetes were assigned to
      two groups: the intervention group (n 30) and the control group (n 25). The
      intervention group received a daily supplement of 10 g resistant dextrin and the
      control group received a similar amount of maltodextrin as placebo for 8 weeks.
      Fasting plasma glucose (FPG), HbA1c, insulin, high-sensitivity C-reactive protein
      (hs-CRP), IL-6, TNF-alpha, malondialdehyde (MDA) and serum endotoxin
      concentrations were measured before and after the intervention. Data were
      analysed using SPSS (version 13). Paired and unpaired t tests and ANCOVA were
      used to compare quantitative variables after the intervention. Patients
      supplemented with resistant dextrin exhibited a significant decrease in fasting
      insulin (20.1 pmol/l, 22.8%), homeostasis model assessment of insulin resistance
      (1.3, 24.9%), quantitative insulin sensitivity check index (0.2, 7.2%), IL-6 (1.4
      pg/ml, 28.4 %), TNF-alpha (5.4 pg/ml, 18.8 %), MDA (1.2 nmol/ml, 25.6 %) and
      endotoxin (6.2 endotoxin units/ml, 17.8%) concentrations than those supplemented
      with maltodextrin (P< 0.05). Decreases in FPG (0.05 mmol/l, 0.6%), HbA1c (0.5%,
      9.6%) and hs-CRP (2.7 ng/ml, 35.1%) concentrations in the resistant dextrin group
      were not significant when compared with the maltodextrin group. In conclusion,
      resistant dextrin supplementation can modulate inflammation and improve insulin
      resistance in women with type 2 diabetes.

PMID- 27028003
TI  - The Diet from the North: a new paradigm of a healthy dietary pattern?

PMID- 27028004
TI  - Near-infrared Spectroscopy Monitoring During Cardiac Arrest: A Systematic Review
      and Meta-analysis.
AB  - BACKGROUND: Tissue oximetry using near-infrared spectroscopy (NIRS) is a
      noninvasive monitor of cerebral oxygenation. This new technology has been used
      during cardiac arrest (CA) because of its ability to give measures in low-blood
      flow situations. The aim of this study was to assess the evidence regarding the
      association between the types of NIRS measurements (mean, initial, and highest
      values) and resuscitation outcomes (return of spontaneous circulation [ROSC],
      survival to discharge, and good neurologic outcome) in patients undergoing
      cardiopulmonary resuscitation. METHODS: This review was registered (Prospero
      CRD42015017380) and is reported as per the PRISMA guidelines. Medline, Embase,
      and CENTRAL were searched. All studies, except case reports and case series of
      fewer than five patients, reporting on adults that had NIRS monitoring during CA
      were eligible for inclusion. Two reviewers assessed the quality of the included
      articles and extracted the data. The outcome effect was standardized using
      standardized mean difference (SMD). RESULTS: Twenty nonrandomized observational
      studies (15 articles and five conference abstracts) were included in this review,
      for a total of 2,436 patients. We found a stronger association between ROSC and
      mean NIRS values (SMD = 1.33; 95% confidence interval [CI] = 0.92 to 1.74) than
      between ROSC and initial NIRS measurements (SMD = 0.51; 95% CI = 0.23 to 0.78).
      There was too much heterogeneity among the highest NIRS measurements group to
      perform meta-analysis. Only two of the 75 patients who experienced ROSC had a
      mean NIRS saturation under 30%. Patients who survived to discharge and who had
      good neurologic outcome displayed superior combined initial and mean NIRS values
      than their counterparts (SMD = 1.63; 95% CI = 1.34 to 1.92; and SMD = 2.12; 95%
      CI = 1.14 to 3.10). CONCLUSIONS: Patients with good resuscitation outcomes have
      significantly higher NIRS saturations during resuscitation than their
      counterparts. The types of NIRS measurements during resuscitation influenced the
      association between ROSC and NIRS saturation. Prolonged failure to obtain a NIRS
      saturation higher than 30% may be included in a multimodal approach to the
      decision of terminating resuscitation efforts (Class IIb, Level of Evidence C
      Limited Data).

PMID- 27028005
TI  - ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium--Effects of
      Prochloraz.
AB  - Some chemicals are ligands to efflux transporters which may result in high
      concentrations in milk. Limited knowledge is available on the influence of
      maternal exposure to chemicals on the expression and function of transporters in
      the lactating mammary gland. We determined gene expression of ABC and SLC
      transporters in murine mammary tissue of different gestation and lactation
      stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes
      and in bovine mammary tissue and cells (BME-UV). Effects on transporter
      expression and function of the imidazole fungicide prochloraz, previously
      reported to influence BCRP in mammary cells, was investigated on transporter
      expression and function in the two cell lines. Transporters studied were BCRP,
      MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in
      murine mammary glands were increased during gestation and lactation, whereas
      MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins.
      All transporters measured in mammary glands of mice were detected in bovine
      mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME
      UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both
      differentiated HC11 and BME-UV cells and increased protein function in HC11
      cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In
      conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV)
      mammary epithelial cells can be applied to characterize expression and function
      of transporters as well as effects of contaminants on the mammary transporters.
      An altered expression, induced by a drug or toxic chemical, on any of the
      transporters expressed in the mammary epithelial cells during lactation may
      modulate the well-balanced composition of nutrients and/or secretion of
      contaminants in milk with potential adverse effects on breast-fed infants and
      dairy consumers. 

PMID- 27028006
TI  - Comparison of anti-inflammatory mechanisms of mango (Mangifera Indica L.) and
      pomegranate (Punica Granatum L.) in a preclinical model of colitis.
AB  - SCOPE: Tannin-rich fruits have been evaluated as alternative prevention
      strategies for colorectal cancer based on their anti-inflammatory properties.
      This study compared tannin-rich preparations from mango (rich in gallotannins)
      and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced
      colitis model. METHODS AND RESULTS: In rats, mango and pomegranate beverages
      decreased intestinal inflammation and the levels of pro-inflammatory cytokines in
      mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total
      protein expression of the IGF-1R-AKT/mTOR axis and downregulated mRNA expression
      of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as
      Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding of
      docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the
      activity of the enzyme. Ellagic acid docked effectively into the catalytic
      domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated
      CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure
      compounds, corroborated the predictions made in silico. CONCLUSION: Mango
      polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols
      downregulate the mTOR downstream pathway through reductions in ERK1/2. These
      results suggest that extracts rich in gallo- and ellagitannins act on different
      molecular targets in the protection against ulcerative colitis.

PMID- 27028007
TI  - The Identification of Novel Diagnostic Marker Genes for the Detection of Beer
      Spoiling Pediococcus damnosus Strains Using the BlAst Diagnostic Gene findEr.
AB  - As the number of bacterial genomes increases dramatically, the demand for easy to
      use tools with transparent functionality and comprehensible output for applied
      comparative genomics grows as well. We present BlAst Diagnostic Gene findEr
      (BADGE), a tool for the rapid prediction of diagnostic marker genes (DMGs) for
      the differentiation of bacterial groups (e.g. pathogenic / nonpathogenic). DMG
      identification settings can be modified easily and installing and running BADGE
      does not require specific bioinformatics skills. During the BADGE run the user is
      informed step by step about the DMG finding process, thus making it easy to
      evaluate the impact of chosen settings and options. On the basis of an example
      with relevance for beer brewing, being one of the oldest biotechnological
      processes known, we show a straightforward procedure, from phenotyping, genome
      sequencing, assembly and annotation, up to a discriminant marker gene PCR assay,
      making comparative genomics a means to an end. The value and the functionality of
      BADGE were thoroughly examined, resulting in the successful identification and
      validation of an outstanding novel DMG (fabZ) for the discrimination of harmless
      and harmful contaminations of Pediococcus damnosus, which can be applied for
      spoilage risk determination in breweries. Concomitantly, we present and compare
      five complete P. damnosus genomes sequenced in this study, finding that the
      ability to produce the unwanted, spoilage associated off-flavor diacetyl is a
      plasmid encoded trait in this important beer spoiling species. 

PMID- 27028008
TI  - Can Plan Recommendations Improve the Coverage Decisions of Vulnerable Populations
      in Health Insurance Marketplaces?
AB  - OBJECTIVE: The Affordable Care Act's marketplaces present an important
      opportunity for expanding coverage but consumers face enormous challenges in
      navigating through enrollment and re-enrollment. We tested the effectiveness of a
      behaviorally informed policy tool--plan recommendations--in improving marketplace
      decisions. STUDY SETTING: Data were gathered from a community sample of 656 lower
      income, minority, rural residents of Virginia. STUDY DESIGN: We conducted an
      incentive-compatible, computer-based experiment using a hypothetical marketplace
      like the one consumers face in the federally-facilitated marketplaces, and
      examined their decision quality. Participants were randomly assigned to a control
      condition or three types of plan recommendations: social normative, physician,
      and government. For participants randomized to a plan recommendation condition,
      the plan that maximized expected earnings, and minimized total expected annual
      health care costs, was recommended. DATA COLLECTION: Primary data were gathered
      using an online choice experiment and questionnaire. PRINCIPAL FINDINGS: Plan
      recommendations resulted in a 21 percentage point increase in the probability of
      choosing the earnings maximizing plan, after controlling for participant
      characteristics. Two conditions, government or providers recommending the lowest
      cost plan, resulted in plan choices that lowered annual costs compared to
      marketplaces where no recommendations were made. CONCLUSIONS: As millions of
      adults grapple with choosing plans in marketplaces and whether to switch plans
      during open enrollment, it is time to consider marketplace redesigns and leverage
      insights from the behavioral sciences to facilitate consumers' decisions.

PMID- 27028009
TI  - Myocardial triggers involved in activation of remote ischaemic preconditioning.
AB  - NEW FINDINGS: What is the central question of this study? Ischaemia-reperfusion
      of peripheral tissues protects the heart from subsequent myocardial ischaemia
      reperfusion injury, a phenomenon referred to as remote ischaemic preconditioning
      (rIPC). This study evaluated the possible myocardial triggers of rIPC. What is
      the main finding and its importance? Remote ischaemic preconditioning reduces
      infarct size through a vagal pathway and a mechanism involving phosphorylation of
      Akt and endothelial nitric oxide synthase, opening of mitochondrial ATP-dependent
      K(+) channels and an increase in mitochondrial H2 O2 production. All these
      phenomena occur before the myocardial ischaemia; hence, they could act as
      'triggers' of rIPC. It has been proposed that remote ischaemic preconditioning
      (rIPC) activates a parasympathetic neural pathway. However, the myocardial
      intracellular mechanism of rIPC remains unclear. Here, we characterized some of
      the intracellular signals participating as rIPC triggers. Isolated rat hearts
      were subjected to 30 min of global ischaemia and 120 min of reperfusion (Non-rIPC
      group). In a second group, before the isolation of the heart, an rIPC protocol
      (three cycles of hindlimb ischaemia-reperfusion) was performed. The infarct size
      was measured with tetrazolium staining. Expression/phosphorylation of Akt and
      endothelial nitric oxide synthase (eNOS) and mitochondrial H2 O2 production were
      evaluated at the end of the rIPC protocol, before myocardial ischaemia
      reperfusion. The rIPC significantly decreased the infarct size and induced Akt
      and eNOS phosphorylation. The protective effect on infarct size was abolished by
      cervical vagal section, l-NAME (an NO synthesis inhibitor) and 5-hydroxydecanoate
      (a mitochondrial ATP-dependent K(+) channel blocker). Mitochondrial production of
      H2 O2 was increased by rIPC, whereas it was abolished by cervical vagal section,
      l-NAME and 5-hydroxydecanoate. We conclude that rIPC activates a parasympathetic
      vagal pathway and a mechanism involving the phosphorylation of Akt and eNOS, the
      opening of mitochondrial ATP-dependent K(+) channels and the release of H2 O2 by
      the mitochondria. All these phenomena occur before myocardial ischaemia and could
      act as triggers of rIPC.

PMID- 27028010
TI  - Assessing Lymphatic Filariasis Data Quality in Endemic Communities in Ghana,
      Using the Neglected Tropical Diseases Data Quality Assessment Tool for Preventive
      Chemotherapy.
AB  - BACKGROUND: The activities of the Global Programme for the Elimination of
      Lymphatic Filariasis have been in operation since the year 2000, with Mass Drug
      Administration (MDA) undertaken yearly in disease endemic communities.
      Information collected during MDA-such as population demographics, age, sex, drugs
      used and remaining, and therapeutic and geographic coverage-can be used to assess
      the quality of the data reported. To assist country programmes in evaluating the
      information reported, the WHO, in collaboration with NTD partners, including
      ENVISION/RTI, developed an NTD Data Quality Assessment (DQA) tool, for use by
      programmes. This study was undertaken to evaluate the tool and assess the quality
      of data reported in some endemic communities in Ghana. METHODS: A cross sectional
      study, involving review of data registers and interview of drug distributors,
      disease control officers, and health information officers using the NTD DQA tool,
      was carried out in selected communities in three LF endemic Districts in Ghana.
      Data registers for service delivery points were obtained from District health
      office for assessment. The assessment verified reported results in comparison
      with recounted values for five indicators: number of tablets received, number of
      tablets used, number of tablets remaining, MDA coverage, and population treated.
      Furthermore, drug distributors, disease control officers, and health information
      officers (at the first data aggregation level), were interviewed, using the DQA
      tool, to determine the performance of the functional areas of the data management
      system. FINDINGS: The results showed that over 60% of the data reported were
      inaccurate, and exposed the challenges and limitations of the data management
      system. The DQA tool is a very useful monitoring and evaluation (M&E) tool that
      can be used to elucidate and address data quality issues in various NTD control
      programmes.

PMID- 27028011
TI  - Feasibility and relevance of level I substation node counts in oropharyngeal
      carcinoma.
AB  - BACKGROUND: The inclusion of level I in neck dissections for oropharyngeal
      carcinoma remains controversial. Our objectives were to evaluate the feasibility
      and relevance of substation node counts in level I of the neck dissection and to
      determine the specific substation location of metastases in level I in
      oropharyngeal carcinoma. METHODS: Sixty specimens were retrospectively analyzed
      after an orientation using a new paradigm of demarcating level I specimens into 8
      substations. RESULTS: Three of the specimens (5%) in this study showed nodal
      metastasis in level I, one each in 3 different substations. All positive nodes in
      level I were associated with N+ disease in level II with 2 being radiographically
      occult (3.3%). Average total node count for level I was 8.1 (range, 2-19).
      CONCLUSION: In oropharyngeal carcinoma, substation level I node quantification is
      feasible and relevant. This study shows a 5% risk to level I with metastasis in 3
      different substations. (c) 2016 Wiley Periodicals, Inc. Head Neck 38:1194-1200,
      2016.

PMID- 27028012
TI  - Vascular plug closure of a complex coronary artery fistula.
AB  - This case report describes the percutaneous closure of a complex coronary artery
      fistula through the successful deployment of a vascular plug. It particularly
      highlights the technical challenges of percutaneously treating complex distal
      type fistulae. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028013
TI  - From the Editor's Desk: Sailing Osler's Uncharted Sea with Innovation and
      Collaboration at the Helm.

PMID- 27028014
TI  - Comparison of efficacy of products containing azelaic acid in melasma treatment.
AB  - BACKGROUND: Melasma is one of the most frequently diagnosed hyperpigmentation
      changes on the skin of women's faces. Nearly 30% of women using oral estrogen
      therapy struggle with this problem. A common way of reducing melasma is the
      application of azelaic acid products. AIM: Comparison of efficacy of three
      dermocosmetic products, containing azelaic acid, in the reduction in melasma for
      women aged 35-55. MATERIAL AND METHODS: A group of 60 women diagnosed with
      melasma were divided into three even, twenty-person subgroups. Each subgroup was
      assigned one dermocosmetic product containing azelaic acid. For 24 weeks, the
      patients applied the assigned product twice a day. The level of the colorant
      within the hyperpigmentation was marked before the treatment, after 1 month,
      after 3 months, and after 6 months of therapy. The pigmentation was measured
      using Mexameter((r)) (Courage + Khazaka electronic, Germany). In addition, during
      each inspection, the patients' level of hydration, elasticity, and intensity of
      erythema was checked using Corneometer((r)) , Reviscometer((r)) . RESULTS: All
      dermocosmetics containing azelaic acid that were applied significantly
      contributed to the reduction in pigment in the pigmentary lesion. The largest
      decrease in the amount of pigment was observed in the first 3 months of use of
      the products. A combination containing 20% azelaic acid and mandelic acid, phytic
      acid, 4N-butyl resorcinol, and ferulic acid proved to be the most effective
      dermocosmetic III (Sesderma, Valencia, Spain). CONCLUSIONS: Dermocosmetics
      containing azelaic acid significantly contribute to the clearing of melasma. The
      effect depends on the treatment time, the acid concentration, and addition of
      other components.

PMID- 27028015
TI  - Development and psychometric properties of ECPICID-AVC to measure informal
      caregivers' skills when caring for older stroke survivors at home.
AB  - INTRODUCTION: Informal caregivers provide a significant part of the total care
      needed by dependent older people poststroke. Although informal care is often the
      preferred option of those who provide and those who receive informal care,
      informal caregivers often report lack of preparation to take care of older
      dependent people. This article outlines the development and psychometric testing
      of informal caregivers' skills when providing care to older people after a stroke
      - ECPICID-AVC. DESIGN: Prospective psychometric instrument validation study.
      METHODS: Eleven experts participated in a focus group in order to delineate,
      develop and validate the instrument. Data were gathered among adult informal
      caregivers (n = 186) living in the community in Northern Portugal from August
      2013 to January 2014. RESULTS: The 32-item scale describes several aspects of
      informal caregiver's skills. The scale has eight factors: skill to feed/hydrate
      by nasogastric feeding, skill to assist the person in personal hygiene, skill to
      assist the person for transferring, skill to assist the person for positioning,
      skill to provide technical aids, skill to assist the person to use the toilet,
      skill to feed/hydrate and skill to provide technical aids for
      dressing/undressing. Analysis demonstrated adequate internal consistency
      (Cronbach's alpha = 0.83) and good temporal stability 0.988 (0.984-0.991).
      CONCLUSION: The psychometric properties of the measurement tool showed acceptable
      results allowing its implementation in clinical practice by the nursing community
      staff for evaluating practical skills in informal caregivers when providing care
      to older stroke survivors living at home.

PMID- 27028016
TI  - Efficiency of bimaxillary advancement surgery in increasing the volume of the
      upper airways: a systematic review of observational studies and meta-analysis.
AB  - Postsurgical changes of the airways have become a great point of interest because
      it has been reported that maxillomandibular advancement surgery can improve or
      eliminate obstructive sleep apnea; however, its treatment effectiveness is still
      controversial. The purpose of this systematic review and meta-analysis was to
      assess the effectiveness of maxillomandibular advancement surgery to increase
      upper airway volume in adults, comparing before and after treatment.
      Bibliographic searches of observational studies with no restriction of year or
      language were performed in the electronic databases PubMed, Scopus, ScienceDirect
      and SciELO for articles published up to April 2015. After verification of
      duplicate records, 1860 articles were examined. Of these, ten met the eligibility
      criteria, of which three were excluded for having poor methodological quality.
      The other seven articles were included in the systematic review and six in the
      meta-analysis, representing 83 patients. One study whose data were not given in
      absolute values was excluded from the meta-analysis. The meta-analysis showed a
      statistically significant difference between the averages of upper airway volume
      before and after surgery {7.86 cm3 [95 % CI (6.22, 9.49), p = 1.00)}. Clinical
      evidence suggests that the upper airway volume is increased after
      maxillomandibular advancement surgery.

PMID- 27028017
TI  - Estimating and Predicting Metal Concentration Using Online Turbidity Values and
      Water Quality Models in Two Rivers of the Taihu Basin, Eastern China.
AB  - Turbidity (T) has been widely used to detect the occurrence of pollutants in
      surface water. Using data collected from January 2013 to June 2014 at eleven
      sites along two rivers feeding the Taihu Basin, China, the relationship between
      the concentration of five metals (aluminum (Al), titanium (Ti), nickel (Ni),
      vanadium (V), lead (Pb)) and turbidity was investigated. Metal concentration was
      determined using inductively coupled plasma mass spectrometry (ICP-MS). The
      linear regression of metal concentration and turbidity provided a good fit, with
      R(2) = 0.86-0.93 for 72 data sets collected in the industrial river and R(2) =
      0.60-0.85 for 60 data sets collected in the cleaner river. All the regression
      presented good linear relationship, leading to the conclusion that the occurrence
      of the five metals are directly related to suspended solids, and these metal
      concentration could be approximated using these regression equations. Thus, the
      linear regression equations were applied to estimate the metal concentration
      using online turbidity data from January 1 to June 30 in 2014. In the prediction,
      the WASP 7.5.2 (Water Quality Analysis Simulation Program) model was introduced
      to interpret the transport and fates of total suspended solids; in addition,
      metal concentration downstream of the two rivers was predicted. All the relative
      errors between the estimated and measured metal concentration were within 30%,
      and those between the predicted and measured values were within 40%. The
      estimation and prediction process of metals' concentration indicated that
      exploring the relationship between metals and turbidity values might be one
      effective technique for efficient estimation and prediction of metal
      concentration to facilitate better long-term monitoring with high temporal and
      spatial density.

PMID- 27028018
TI  - Strings-to-Rings Transition and Antiparallel Dipole Alignment in Two-Dimensional
      Methanols.
AB  - Structural order emerging in the liquid state necessitates a critical degree of
      anisotropy of the molecules. For example, liquid crystals and Langmuir monolayers
      require rod- or disc-shaped and long-chain amphiphilic molecules, respectively,
      to break the isotropic symmetry of liquids. In this Letter we present results
      from molecular dynamics simulations demonstrating that in two-dimensional
      liquids, a significantly smaller degree of anisotropy is sufficient to allow
      structural organization. In fact, the condensed phase of the smallest amphiphilic
      molecule, methanol, confined between two, or adsorbed on, graphene sheets forms a
      monolayer characterized by long chains of molecules. Intrachain interactions are
      dominated by hydrogen bonds, whereas interchain interactions are dispersive. Upon
      a decrease in density toward a gaslike state, these strings are transformed into
      rings. The two-dimensional liquid phase of methanol undergoes another transition
      upon cooling; in this case, the order-disorder transition is characterized by a
      low-temperature phase in which the hydrogen bond dipoles of neighboring strings
      adopt an antiparallel orientation.

PMID- 27028019
TI  - Emerging Diversity of the Cobalamin-Dependent Methyltransferases Involving
      Radical-Based Mechanisms.
AB  - Cobalamins comprise a group of cobalt-containing organometallic cofactors that
      play important roles in cellular metabolism. Although many cobalamin-dependent
      methyltransferases (e.g., methionine synthase MetH) have been extensively
      studied, a new group of methyltransferases that are cobalamin-dependent and
      utilize radical chemistry in catalysis is just beginning to be appreciated. In
      this Concept article, we summarize recent advances in the understanding of the
      radical-based and cobalamin-dependent methyltransferases and discuss the
      functional and mechanistic diversity of this emerging class of enzymes.

PMID- 27028020
TI  - Generalized keratosis pilaris-like eruptions in a chronic myelogenous leukemia
      patient treated with nilotinib.

PMID- 27028023
TI  - Gut Microbiota: A Key Modulator of Intestinal Healing in Inflammatory Bowel
      Disease.
AB  - Mucosal healing (MH) represents a crucial factor for maintaining gut homeostasis.
      Indeed, in inflammatory bowel disease, MH has become the standard therapeutical
      target, because it is associated with more effective disease control, more
      frequent steroid-free remission, lower rates of hospitalization and surgery, and
      improved quality of life. In this scenario, gut microbiota is a crucial player in
      modulating intestinal repair and regeneration process. It can act on the tumor
      necrosis factor-alpha production, modulation of reactive oxygen and nitrogen
      species, activity of matrix metalloproteinases and on many other mechanisms
      strictly involved in restoring gut health. In this review, we analyze and review
      the literature on the role of gut microbiota in sustaining mucosal injury and
      achieving MH. 

PMID- 27028024
TI  - Is Western Australia's rural surgical workforce going to sustain the future? A
      quantitative and qualitative analysis.
AB  - Objective Despite public interest in the rural workforce, there are few published
      data on the geographical distribution of Australia's rural surgeons, their
      practice skill set, career stage or work-life balance (on-call burden).
      Similarly, there has not been a peer-reviewed skills audit of rural training
      opportunities for surgical trainees. The present study undertook this baseline
      assessment for Western Australia (WA), which has some of the most remote practice
      areas in Australia. Methods Hospital staff from all WA Country Health Service
      hospitals with surgical service (20 of 89 rural health services) were contacted
      by telephone. A total of 18 of 20 provided complete data. The study questionnaire
      explored hospital and practice locations of practicing rural surgeons, on-call
      rosters, career stage, practice skill set and the availability of surgical
      training positions. Data were tabulated in excel and geographic information
      system geocoded. Descriptive statistics were calculated in Excel. Results Of the
      seven health regions for rural Western Australia, two (28.6%) were served by
      resident surgeons at a ratio consistent with Royal Australasian College of
      Surgeons (RACS) guidelines. General surgery was offered in 16 (89%) hospitals. In
      total, 16 (89%) hospitals were served by fly-in, fly-out (FIFO) surgical
      services. Two hospitals with resident surgeons did not use FIFO services, but all
      hospitals without resident surgeons were served by FIFO surgical specialists. The
      majority of resident surgeons (62.5%) and FIFO surgeons (43.2%) were perceived to
      be mid-career by hospital staff members. Three hospitals (16.7%) offered all
      eight of the identified surgical skill sets, but 16 (89%) offered general
      surgery. Conclusions Relatively few resident rural surgeons are servicing large
      areas of WA, assisted by the widespread provision of FIFO surgical services. The
      present audit demonstrates strength in general surgical skills throughout
      regional WA, and augers well for the training of general surgeons. What is known
      about the topic? A paper published in 1998 suggested that Australia's rural
      surgeons were soon to reach retirement age. However, there have been no published
      peer-reviewed papers on Australia's surgical workforce since then. More recent
      workforce statistics released from the RACS suggest that the rural workforce is
      in crisis. What does this paper add? This paper provides up-to-date whole-of
      state information for WA, showing where surgical services are being provided and
      by whom, giving a precise geographical spread of the workforce. It shows the
      skill set and on-call rosters of these practitioners. What are the implications
      for practitioners? The present study provides geographical workforce data, which
      is important to health planners, the general public and surgeons considering
      where to practice. In particular, these data are relevant to trainees considering
      their rural training options.

PMID- 27028025
TI  - Glycaemic control and risk of incident urinary incontinence in women with Type 1
      diabetes: results from the Diabetes Control and Complications Trial and
      Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
AB  - AIMS: To study the impact of glycaemic control on urinary incontinence in women
      who participated in the Diabetes Control and Complications Trial (DCCT; 1983
      1993) and its observational follow-up study, the Epidemiology of Diabetes
      Interventions and Complications (EDIC; 1994-present). METHODS: Study participants
      were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC
      follow-up, the urological assessment questionnaire (UroEDIC). Urinary
      incontinence was defined as self-reported involuntary leakage of urine that
      occurred at least weekly. Incident urinary incontinence was defined as weekly
      urinary incontinence present at EDIC year 17 but not at EDIC year 10.
      Multivariable regression models were used to examine the association of incident
      urinary incontinence with comorbid prevalent conditions and glycaemic control
      (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%)
      women with Type 1 diabetes (mean age 43.6 +/- 6.3 years at EDIC year 10) reported
      incident urinary incontinence at EDIC year 17. When adjusted for clinical
      covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI,
      insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract
      infection in the last year), the mean EDIC HbA1c was associated with increased
      odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per
      mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase).
      CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c
      levels in women with Type 1 diabetes, independent of other recognized risk
      factors. These results suggest the potential for women to modify their risk of
      urinary incontinence with improved glycaemic control. (Clinical Trials Registry
      no: NCT00360815 and NCT00360893).

PMID- 27028026
TI  - How Do Residents Spend Their Shift Time? A Time and Motion Study With a
      Particular Focus on the Use of Computers.
AB  - PURPOSE: To understand how much time residents spend using computers compared
      with other activities, and what residents use computers for. METHOD: This time
      and motion study was conducted in June and July 2010 at NewYork
      Presbyterian/Columbia University Medical Center with seven residents (first-,
      second-, and third-year) on the general medicine service. An experienced observer
      shadowed residents during a single day shift, captured all their activities using
      an iPad application, and took field notes. The activities were captured using a
      validated taxonomy of clinical activities, expanded to describe computer-based
      activities with a greater level of detail. RESULTS: Residents spent 364.5 minutes
      (50.6%) of their shift time using computers, compared with 67.8 minutes (9.4%)
      interacting with patients. In addition, they spent 292.3 minutes (40.6%) talking
      with others in person, 186.0 minutes (25.8%) handling paper notes, 79.7 minutes
      (11.1%) in rounds, 80.0 minutes (11.1%) walking or waiting, and 54.0 minutes
      (7.5%) talking on the phone. Residents spent 685 minutes (59.6%) multitasking.
      Computer-based documentation activities amounted to 189.9 minutes (52.1%) of all
      computer-based activities time, with 128.7 minutes (35.3%) spent writing notes
      and 27.3 minutes (7.5%) reading notes composed by others. CONCLUSIONS: The study
      showed that residents spent considerably more time interacting with computers
      (over 50% of their shift time) than in direct contact with patients (less than
      10% of their shift time). Some of this may be due to an increasing reliance on
      computing systems for access to patient data, further exacerbated by
      inefficiencies in the design of the electronic health record.

PMID- 27028027
TI  - Feasibility and Outcomes of Implementing a Portfolio Assessment System Alongside
      a Traditional Grading System.
AB  - PURPOSE: Portfolios are a powerful tool to collect and evaluate evidence of
      medical students' competence across time. However, comprehensive portfolio
      assessment systems that are implemented alongside traditional graded curricula at
      medical schools in the United States have not been described in the literature.
      This study describes the development and implementation of a longitudinal
      competency-based electronic portfolio system alongside a graded curriculum at a
      relatively large U.S. medical school. METHOD: In 2009, the authors developed a
      portfolio system that served as a repository for all student assessments
      organized by competency domain. Five competencies were selected for a
      preclerkship summative portfolio review. Students submitted reflections on their
      performance. In 2014, four clinical faculty members participated in standard
      setting activities and used expert judgment and holistic review to rate students'
      competency achievement as "progressing toward competence," "progressing toward
      competence with some concern," or "progressing toward competence pending
      remediation." Follow-up surveys measured students' and faculty members'
      perceptions of the process. RESULTS: Faculty evaluated 156 portfolios and showed
      high levels of agreement in their ratings. The majority of students achieved the
      "progressing toward competence" benchmark in all competency areas. However, 31
      students received at least one concerning rating, which was not reflected in
      their course grades. Students' perceptions of the system's ability to foster self
      assessment were mixed. CONCLUSIONS: The portfolio review process allowed faculty
      to identify students with a concerning rating in a behavioral competency who
      would not have been identified in a traditional grading system. Identification of
      these students allows for intervention and early remediation.

PMID- 27028028
TI  - Focusing on the Formative: Building an Assessment System Aimed at Student Growth
      and Development.
AB  - This Perspective addresses the need for an integrated system of formative and
      summative assessment in undergraduate medical education with a focus on the
      formative. While acknowledging the importance of summative assessment, which asks
      whether trainees have met criteria for progression, the authors propose that a
      formatively focused assessment system can best accomplish a central task of
      competency-based medical education: transmitting feedback to learners in a format
      and a manner that will help them to improve, develop, and grow. Formative
      assessment should not be seen as a set of singular events but, rather, as a
      process that is organized and integrated over time, much like the cycle of
      quality improvement in medicine. To justify this position, the authors discuss
      its conceptual underpinnings and rationale, including the need to prepare
      learners for the formatively focused assessment system of graduate medical
      education. Next, the authors identify assessment strategies that could be
      employed, as well as the characteristics of an institutional culture and the
      learner-teacher relationship necessary for a learner-centered, improvement
      focused assessment system to succeed. Finally, an infrastructure for such a
      system is proposed. This consists of a foundation of well-articulated and
      disseminated milestones for achievement and four pillars: faculty development,
      learner development, longitudinal academic advising and coaching, and
      documentation of developing competence. The authors conclude by suggesting that
      the guidelines proposed are analogous to the principles of continuity and
      coordination of care, so much valued in the world of medicine yet often
      overlooked in the world of education.

PMID- 27028029
TI  - Establishing an Integrative Medicine Program Within an Academic Health Center:
      Essential Considerations.
AB  - Integrative medicine (IM) refers to the combination of conventional and
      "complementary" medical services (e.g., chiropractic, acupuncture, massage,
      mindfulness training). More than half of all medical schools in the United States
      and Canada have programs in IM, and more than 30 academic health centers
      currently deliver multidisciplinary IM care. What remains unclear, however, is
      the ideal delivery model (or models) whereby individuals can responsibly access
      IM care safely, effectively, and reproducibly in a coordinated and cost-effective
      way.Current models of IM across existing clinical centers vary tremendously in
      their organizational settings, principal clinical focus, and services provided;
      practitioner team composition and training; incorporation of research activities
      and educational programs; and administrative organization (e.g., reporting
      structure, use of medical records, scope of clinical practice) and financial
      strategies (i.e., specific business plans and models for sustainability).In this
      article, the authors address these important strategic issues by sharing lessons
      learned from the design and implementation of an IM facility within an academic
      teaching hospital, the Brigham and Women's Hospital at Harvard Medical School;
      and review alternative options based on information about IM centers across the
      United States.The authors conclude that there is currently no consensus as to how
      integrative care models should be optimally organized, implemented, replicated,
      assessed, and funded. The time may be right for prospective research in "best
      practices" across emerging models of IM care nationally in an effort to
      standardize, refine, and replicate them in preparation for rigorous cost
      effectiveness evaluations.

PMID- 27028030
TI  - Shortening the Miles to the Milestones: Connecting EPA-Based Evaluations to ACGME
      Milestone Reports for Internal Medicine Residency Programs.
AB  - The Next Accreditation System requires internal medicine training programs to
      provide the Accreditation Council for Graduate Medical Education (ACGME) with
      semiannual information about each resident's progress in 22 subcompetency
      domains. Evaluation of resident "trustworthiness" in performing entrustable
      professional activities (EPAs) may offer a more tangible assessment construct
      than evaluations based on expectations of usual progression toward competence.
      However, translating results from EPA-based evaluations into ACGME milestone
      progress reports has proven to be challenging because the constructs that
      underlay these two systems differ.The authors describe a process to bridge the
      gap between rotation-specific EPA-based evaluations and ACGME milestone
      reporting. Developed at the University of Washington in 2012 and 2013, this
      method involves mapping EPA-based evaluation responses to "milestone elements,"
      the narrative descriptions within the columns of each of the 22 internal medicine
      subcompetencies. As faculty members complete EPA-based evaluations, the mapped
      milestone elements are automatically marked as "confirmed." Programs can maintain
      a database that tallies the number of times each milestone element is confirmed
      for a resident; these data can be used to produce graphical displays of resident
      progress along the internal medicine milestones.Using this count of milestone
      elements allows programs to bridge the gap between faculty assessments of
      residents based on rotation-specific observed activities and semiannual ACGME
      reports based on the internal medicine milestones. Although potentially useful
      for all programs, this method is especially beneficial to large programs where
      clinical competency committee members may not have the opportunity for direct
      observation of all residents.

PMID- 27028031
TI  - A Multidisciplinary Housestaff-Led Initiative to Safely Reduce Daily Laboratory
      Testing.
AB  - PURPOSE: Provision of high-value care is a milestone in physician training. The
      authors evaluated the effect of a housestaff-led initiative on laboratory testing
      rates. METHOD: Vanderbilt University Medical Center's Choosing Wisely steering
      committee, led by housestaff with faculty advisors, sought to reduce unnecessary
      daily basic metabolic panel (BMP) and complete blood count (CBC) testing on
      inpatient general medicine and surgical services. Intervention services received
      a didactic session followed by regular data feedback with goal rates and peer
      comparison. Testing rates during January 1, 2013-February 9, 2015, were compared
      on intervention services and control services using a difference-in-differences
      analysis and an interrupted time-series analysis with segmented linear
      regression. RESULTS: Compared with concurrent controls, the mean number of BMP
      tests per patient day decreased by an additional 0.23 (95% CI 0.17-0.29) on
      medical housestaff and 0.15 (95% CI 0.09-0.21) on hospitalist intervention
      services. Daily CBC tests decreased by an additional 0.28 (95% CI 0.23-0.33) on
      medical housestaff, 0.08 (95% CI 0.03-0.13) on hospitalist, and 0.12 (95% CI 0.05
      0.20) on surgical housestaff intervention services. Patients with lab-free days
      (0 labs ordered in 24 hours) increased by an additional 4.1 percentage points
      (95% CI 2.1-6.1) on medical housestaff and 9.7 percentage points (95% CI 6.6
      12.8) on hospitalist intervention services. There were no adverse changes in
      length of stay or intensive care unit transfer, in-hospital mortality, or 30-day
      readmission rates. CONCLUSIONS: A housestaff-led intervention utilizing education
      and data feedback with goal setting and peer comparison resulted in safe,
      significant reductions in daily laboratory testing rates.

PMID- 27028032
TI  - Characteristics and Distribution of Graduate Medical Education Training Sites:
      Are We Missing Opportunities to Meet U.S. Health Workforce Needs?
AB  - PURPOSE: Shortages of generalist physicians in primary care and surgery have been
      projected. Residency programs that expose trainees to community-based health
      clinics and rural settings have a greater likelihood of producing physicians who
      later practice in these environments. The objective of this study was to
      characterize the distribution of residency training sites in different settings
      for three high-need specialties-family medicine, internal medicine, and general
      surgery. METHOD: The authors merged 2012 data from the Accreditation Council for
      Graduate Medical Education Accreditation Data System and 2010 data from the
      Centers for Medicare and Medicaid Services hospital cost report to match training
      sites with descriptive data about those locations. They used chi-square tests to
      compare the characteristics and distribution of residency programs and training
      sites in family medicine, internal medicine, and general surgery. RESULTS: The
      authors identified 1,095 residency programs and 3,373 training sites. The
      majority of training occurred in private, not-for-profit hospitals. Only 48 (of
      1,390; 4%) family medicine training sites and 43 (of 936; 5%) internal medicine
      training sites were community-based health clinics. Seventy-eight (6%) family
      medicine sites, 8 (1%) internal medicine sites, and 16 (2%) general surgery sites
      were located in rural settings. One hundred thirty (14%) internal medicine sites
      were Department of Veterans Affairs medical facilities compared with 78 (6%)
      family medicine sites and 94 (9%) general surgery sites (P < .001). CONCLUSIONS:
      Relatively little training occurs in rural or community-based settings. Expanding
      training opportunities in these low-access areas could improve physician supply
      there.

PMID- 27028033
TI  - Feedback to Supervisors: Is Anonymity Really So Important?
AB  - PURPOSE: Research demonstrates that physicians benefit from regular feedback on
      their clinical supervision from their trainees. Several features of effective
      feedback are enabled by nonanonymous processes (i.e., open feedback). However,
      most resident-to-faculty feedback processes are anonymous given concerns of power
      differentials and possible reprisals. This exploratory study investigated
      resident experiences of giving faculty open feedback, advantages, and
      disadvantages. METHOD: Between January and August 2014, nine graduates of a
      Canadian Physiatry residency program that uses open resident-to-faculty feedback
      participated in semistructured interviews in which they described their
      experiences of this system. Three members of the research team analyzed
      transcripts for emergent themes using conventional content analysis. In June
      2014, semistructured group interviews were held with six residents who were
      actively enrolled in the program as a member-checking activity. Themes were
      refined on the basis of these data. RESULTS: Advantages of the open feedback
      system included giving timely feedback that was acted upon (thus enhancing
      residents' educational experiences), and improved ability to receive feedback
      (thanks to observing modeled behavior). Although some disadvantages were noted,
      they were often speculative (e.g., "I think others might have felt ...") and were
      described as outweighed by advantages. Participants emphasized the program's
      "feedback culture" as an open feedback enabler. CONCLUSIONS: The relationship
      between the feedback giver and recipient has been described as influencing the
      uptake of feedback. Findings suggest that nonanonymous practices can enable a
      positive relationship in resident-to-faculty feedback. The benefits of an open
      system for resident-to-faculty feedback can be reaped if a "feedback culture"
      exists.

PMID- 27028034
TI  - A Model for Catalyzing Educational and Clinical Transformation in Primary Care:
      Outcomes From a Partnership Among Family Medicine, Internal Medicine, and
      Pediatrics.
AB  - PURPOSE: To report findings from a national effort initiated by three primary
      care certifying boards to catalyze change in primary care training. METHOD: In
      this mixed-method pilot study (2012-2014), 36 faculty in 12 primary care
      residencies (family medicine, internal medicine, pediatrics) from four
      institutions participated in a professional development program designed to
      prepare faculty to accelerate change in primary care residency training by
      uniting them in a common mission to create effective ambulatory clinical learning
      environments. Surveys administered at baseline and 12 months after initial
      training measured changes in faculty members' confidence and skills, continuity
      clinics, and residency training programs. Feasibility evaluation involved
      assessing participation. The authors compared quantitative data using Wilcoxon
      signed-rank and Bhapkar tests. Observational field notes underwent narrative
      analysis. RESULTS: Most participants attended two in-person training sessions
      (92% and 72%, respectively). Between baseline and 12 months, faculty members'
      confidence in leadership improved significantly for 15/19 (79%) variables
      assessed; their self-assessed skills improved significantly for 21/22 (95%)
      competencies. Two medical home domains ("Continuity of Care," "Support/Care
      Coordination") improved significantly (P < .05) between the two time periods.
      Analyses of qualitative data revealed that interdisciplinary learning communities
      formed during the program and served to catalyze transformational change.
      CONCLUSIONS: Results suggest that improvements in faculty perceptions of
      confidence and skills occurred and that the creation of interdisciplinary
      learning communities catalyzed transformation. Lengthening the intervention
      period, engaging other professions involved in training the primary care
      workforce, and a more discriminating evaluation design are needed to scale this
      model nationally.

PMID- 27028035
TI  - Sleep duration and its impact on adherence in adolescents with type 1 diabetes
      mellitus.
AB  - BACKGROUND: Adherence to the type 1 diabetes (T1D) regimen, while predictive of
      glycemic control, decreases during adolescence. For adolescents, attaining
      adequate sleep is an additional challenge. This study evaluates the impact of
      sleep on adherence in teens with T1D. SUBJECTS: Forty-five adolescents aged 12-18
      yr, with T1D for at least 6 months while on insulin pump therapy. METHODS:
      Adolescents logged their sleep on a written diary for 2 wk. Corresponding insulin
      pump/glucometer downloads as well as sleep habit questionnaires were also
      obtained. RESULTS: Data from 20 girls and 25 boys, with a mean age of 15 +/- 1.6
      yr and mean glycated hemoglobin of 8.7 +/- 1.1% (72 mmol/mol), were analyzed.
      Overall, average sleep was 8.6 +/- 0.9 h per night. Sleep durations were compared
      to the next day's frequency of self-monitored blood glucose (SMBG) and total
      daily insulin bolus frequency. Associations were found between sleep duration and
      youths' SMBG and insulin bolus frequencies (p < 0.03 and p < 0.001,
      respectively). Specifically, a 15- and 20-min increase in sleep was associated
      with one additional SMBG check and one additional insulin bolus, respectively.
      CONCLUSION: Analyses suggest an associated increase in T1D self-management
      behaviors in youths with increased sleep duration. These findings highlight the
      importance of assessing sleep in clinical practice, and encourage further
      research to examine effective strategies to address sleep hygiene as part of
      routine diabetes management.

PMID- 27028036
TI  - Atropinic (Anticholinergic) Burden in Parkinson's Disease.
AB  - Use of atropinic drugs remains controversial in Parkinson's disease (PD) because
      there is insufficient evidence about their efficacy and they can induce serious
      adverse drug reactions. Atropinic risk scales were developed to help to identify
      atropinic drugs in prescription forms and to evaluate their burden in clinical
      practice. In the present review, we discuss the few studies investigating
      atropinic burden in PD and present the results of our study indicating that
      atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions)
      with a clinically significant atropinic burden in around 1 of 6 PD patients.
      Drugs mainly responsible for high values of atropinic burden were those used for
      nonmotor symptoms. Clinically significant atropinic burdens were mainly induced
      by associations of several "low-risk" drugs. Physicians must be aware that in
      addition to classical atropinic antiparkinsonian drugs, many others
      (psychotropics) can contribute to increased atropinic burden in PD patients. (c)
      2016 International Parkinson and Movement Disorder Society.

PMID- 27028037
TI  - Changes in the Chemical Quality of Bone Grafts During Clinical Preparation
      Detected by Raman Spectroscopy.
AB  - METHODOLOGY: We determined the content of amide I, amide III, PO4, CO3, and CH2
      in samples of fresh bone, bone frozen at -80 degrees C thawed once, bone after
      two freeze-thaw cycles, and chemically cleaned bone chips. A total of 750 Raman
      spectra were collected per sample group and the derived quantitative values
      compared statistically by one-way ANOVA. RESULTS: We found statistically
      significant differences between the investigated sample groups differing in their
      treatment already after one freeze-thaw cycle and as well after multiple freeze
      thaw cycles, and/or chemical cleaning. Chemical cleaning decreased the content of
      all measured components compared to the fresh sample as detected by Raman
      spectroscopy. We further used the derived data to calculate the mineral to matrix
      ratios for each sample group. DISCUSSION: Our data indicate that significant
      changes of the chemical quality and mineral to matrix ratio occur during freeze
      thawing and chemical cleaning. At the same time, this study highlights the
      importance of sampling and testing at multiple locations for reliable predictions
      of the chemical composition. We think that it is very desirable to test the
      quality of bone graft material before transfer to a recipient; this might
      ultimately help define parameters to choose the best graft for the patient. It is
      also important to highlight that this is a preliminary study, which shows the
      importance of detecting changes in the chemical quality of bone grafts before
      transfer to the patient.

PMID- 27028038
TI  - Chemoradiotherapy for squamous cell anal carcinoma: a review of prognostic
      factors.
AB  - AIM: Previous literature has sought prognostic factors for the survival of anal
      cancer patients. The present study aimed to determine prognostic factors for
      local disease recurrence, distant metastasis and survival for patients treated
      with radical chemoradiotherapy (CRT) at the Rosemere Cancer Centre, Preston, UK.
      METHOD: Patients treated with CRT for nonmetastatic squamous cell anal cancer
      between September 2000 and January 2013 were studied. Kaplan-Meier and Cox
      regression analysis assessed the prognostic value of age, sex, tumour size, the
      proportion of the anal canal circumference involved (ACCI), nodal disease, tumour
      location and pretreatment haemoglobin. RESULTS: One hundred and 48 patients with
      a mean age of 63 years were studied, of whom 15% suffered local disease
      recurrence and 10% developed distant metastasis. The 5-year overall and cancer
      specific survival rates were 84% and 86%, respectively. Predictors of local
      recurrence were tumour size >5 cm and over two-thirds ACCI (P < 0.01). Predictors
      of distant metastasis and poor survival were tumour size >5 cm (P < 0.01), node
      positive disease on imaging (P < 0.05), over two-thirds ACCI (P < 0.01) and a
      pretreatment haemoglobin level below 130 g/l (P < 0.05). Multivariate analysis
      found large tumour size to be the most significant factor for local recurrence (P
      = 0.002) and survival (P = 0.02) whilst over two-thirds ACCI was most predictive
      of distant metastasis (P < 0.001). Age, gender, palpable lymph nodes and tumour
      location were not of prognostic value for local disease recurrence, distant
      metastasis or survival. CONCLUSION: Tumour size, nodal disease, over two-thirds
      ACCI and low pretreatment haemoglobin confer poorer prognostic and survival
      outcomes. Use of intensity-modulated radiation therapy may allow greater
      radiation doses to be given for locally advanced tumours, thus improving local
      control and survival and reducing morbidity.

PMID- 27028039
TI  - Fluorescent H-Aggregates Hosted by a Charged Cyclodextrin Cavity.
AB  - Most macrocyclic host molecules, including cyclodextrins, usually prevent self
      aggregation of the guest organic molecules, by exploiting inclusion complexation
      of the guest with the host. In this work, it was found that a negatively charged
      beta-cylcodextrin derivative induces aggregation of a well-known amyloid sensing
      dye, Thioflavin-T, and leads to an unprecedented formation of the rarely observed
      emissive H-type aggregates of the dye. 

PMID- 27028040
TI  - Mapping the manuals of madness: Comparing the ICD-10 and DSM-IV-TR using a
      network approach.
AB  - The International Classification of Diseases and Related Health Problems (ICD)
      and the Diagnostic and Statistical Manual of Mental Disorders (DSM) represent
      dominant approaches to diagnosis of mental disorders. However, it is unclear how
      these alternative systems relate to each other when taking into account the
      symptoms that make up the disorders. This study uses a network approach to
      investigate the overlap in structure between diagnostic networks pertaining to
      ICD-10 and DSM-IV-TR. Networks are constructed by representing individual
      symptoms as nodes, and connecting nodes whenever the corresponding symptoms
      feature as diagnostic criteria for the same mental disorder. Results indicate
      that, relative to the DSM-IV-TR network, the ICD-10 network contains (a) more
      nodes, (b) lower level of clustering, and (c) a higher level of connectivity.
      Both networks show features of a small world, and have similar (of "the same")
      high centrality nodes. Comparison to empirical data indicates that the DSM-IV-TR
      network structure follows comorbidity rates more closely than the ICD-10 network
      structure. We conclude that, despite their apparent likeness, ICD-10 and DSM-IV
      TR harbour important structural differences, and that both may be improved by
      matching diagnostic categories more closely to empirically determined network
      structures. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27028041
TI  - Flat field correction for high-throughput imaging of fluorescent samples.
AB  - Vignetting of microscopic images impacts both the visual impression of the images
      and any image analysis applied to it. Especially in high-throughput screening
      high demands are made on an automated image analysis. In our work we focused on
      fluorescent samples and found that two profiles (background and foreground) for
      each imaging channel need to be estimated to achieve a sufficiently flat image
      after correction. We have developed a method which runs completely unsupervised
      on a wide range of assays. By adding a reliable internal quality control we
      mitigate the risk of introducing artefacts into sample images through correction.
      The method requires hundreds of images for the foreground profile, thus limiting
      its application to high-throughput screening where this requirement is fulfilled
      in routine operation.

PMID- 27028042
TI  - Sequence Evolution Under Constraints: Lessons Learned from Sudoku.
AB  - The complex structures of all proteins in nature are outcomes of a random walk
      driven by mutation and selection. Reconstructing the fitness landscape staging
      this process based on first-principle physical rules or experimental measurements
      is difficult. In this article we turn the popular Sudoku game into an artificial
      fitness landscape and use it as a model system to study sequence evolution under
      constraints. The Sudoku rules, which are human-mind friendly, intertwine a rugged
      landscape for sequences composed of digits, mimicking the functional constraints
      felt by a tightly folded protein. Simulated evolution reveals interesting
      properties of the valley-crossing dynamics on this complex landscape. It is found
      that (i) the mutation accumulation rate during valley-crossing is constant among
      different evolutionary pathways and depends on the ruggedness of the landscape;
      (ii) genetic drift and neutral networks play constructive roles during the
      process of searching for novel functions; and (iii) under strong selection, gene
      duplication can speed up the evolution by relaxing, but not completely
      liberating, the redundant copy from selective pressure. Insights gained from this
      prototype model may help us understand the evolution of real proteins. 

PMID- 27028043
TI  - Complexity in Redesigning Depression Care: Comparing Intention Versus
      Implementation of an Automated Depression Screening and Monitoring Program.
AB  - Health care technology promises to improve quality and decrease costs while
      improving the patient experience. A recent trial tested a novel health technology
      that sought to reduce barriers to guideline-recommended depression care by
      coupling automated telephonic patient assessment with provider notification and
      decision support. This study compares the intended effects and the end users'
      experience with using this technology. Responses to semi-structured interviews
      with the leadership and design team (the intention group) were compared with
      responses from health professionals in clinics using the technology (the
      implementation group). Qualitative methods were applied to compare perspectives
      on the role of technology in care delivery and on the technology's impact on
      barriers to providing guideline-recommended care. Four members of the intention
      group and 17 members of the implementation group were interviewed. The 2 groups
      had similar notions of technology's role in care delivery. The technology
      increased provider awareness, empowered midlevel providers, and facilitated
      collaboration among care team members. However, the implementation group
      identified gaps in care processes and in the informatics system that the
      technology did not address, and for which providers remained responsible. The 2
      groups had comparable perspectives on the value and limits of technology in
      improving adherence to guideline-recommended care. However, the intention group
      did not discuss many of the shortcomings identified by the implementation group.
      Also, the interviews suggest that although some barriers persisted and a few new
      ones arose, the technology succeeded in reducing barriers to guideline
      recommended care.

PMID- 27028044
TI  - Tracking gastrointestinal transit of solids in aged rats as pharmacological
      models of chronic dysmotility.
AB  - BACKGROUND: Dysmotility in the gastrointestinal (GI) tract often leads to
      impaired transit of luminal contents leading to symptoms of diarrhea or
      constipation. The aim of this research was to develop a technique using high
      resolution X-ray imaging to study pharmacologically induced aged rat models of
      chronic GI dysmotility that mimic accelerated transit (diarrhea) or constipation.
      The 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist prucalopride was used to
      accelerate transit, and the opioid agonist loperamide was used to delay transit.
      METHODS: Male rats (18 months) were given 0, 1, 2, or 4 mg/kg/day prucalopride or
      loperamide (in dimethyl sulfoxide, DMSO) for 7 days by continuous 7-day dosing.
      To determine the GI region-specific effect, transit of six metallic beads was
      tracked over 12 h using high resolution X-ray imaging. An established rating
      scale was used to classify GI bead location in vivo and the distance beads had
      propagated from the caecum was confirmed postmortem. KEY RESULTS: Loperamide (1
      mg/kg) slowed stomach emptying and GI transit at 9 and 12 h. Prucalopride (4
      mg/kg) did not significantly alter GI transit scores, but at a dose of 4 mg/kg
      beads had moved significantly more distal than the caecum in 12 h compared to
      controls. CONCLUSIONS & INFERENCES: We report a novel high-resolution, non
      invasive, X-ray imaging technique that provides new insights into GI transit
      rates in live rats. The results demonstrate that loperamide slowed overall
      transit in aged rats, while prucalopride increased stomach emptying and
      accelerates colonic transit.

PMID- 27028045
TI  - Progression of stable juvenile osteochondritis dissecans after 10 years of
      meniscectomy of the discoid lateral meniscus.
AB  - Ten years after a meniscectomy of discoid lateral meniscus, a 19-year-old man
      presented a loose body in his right knee with limited range of motion. At the
      time of meniscectomy, a stable osteochondritis dissecans in the lateral femoral
      condyle with a T2 high area in MRI was recognized; however, the lesion was left
      without surgical treatment. We performed fixation of a fragment and osteochondral
      grafting. Surgical treatment for stable juvenile osteochondritis dissecans still
      remains controversial; however, drilling will help to increase the healing
      potential and to prevent lesion progression, especially after meniscectomy that
      alters the mechanical stress on immature osteochondral structures.

PMID- 27028046
TI  - Cryonic Preservation of a Patient Dying from Head Trauma.

PMID- 27028047
TI  - Population-Based Assessment of Unilateral Visual Impairment in the South Indian
      State of Andhra Pradesh: Rapid Assessment of Visual Impairment (RAVI) Project.
AB  - PURPOSE: To assess the prevalence and causes of unilateral visual impairment (VI)
      in the South Indian state of Andhra Pradesh. METHODS: A population-based cross
      sectional study was conducted among individuals aged >=40 years in one urban and
      two rural locations, using rapid assessment methodology. A 2-stage cluster random
      sampling method was used to select 7800 individuals from 156 clusters. Distance
      visual acuity (VA) was assessed using a standard Snellen chart at a distance of 6
      m. Eye examinations were conducted using a torchlight and distance direct
      ophthalmoscopy. Unilateral VI was defined as presenting VA <6/18 in one eye and
      presenting VA >=6/18 in the other, and included moderate unilateral VI (<6/18 to
      6/60) and unilateral blindness (<6/60). RESULTS: In total, 7378 individuals
      (94.6%) were examined. After excluding 918 individuals with VI in the better eye,
      data were analyzed for the remaining 6460 individuals. Among those included in
      the analysis, mean age was 50 years (standard deviation 9.6 years), 46.7% were
      male, 58.9% had no education, and 34.1% were urban residents. The prevalence of
      unilateral VI was 11.3% (95% confidence interval 10.5-12.1%; n = 730).
      Uncorrected refractive error was found to be the leading cause (44%; n = 321) of
      unilateral VI followed by cataract (39.7%; n = 290). CONCLUSIONS: Unilateral VI
      is common in the South Indian state of Andhra Pradesh. As most of this VI can be
      addressed with interventions such as cataract surgery and spectacles, service
      models need to be streamlined to address this need.

PMID- 27028049
TI  - The impact of positive affect on health cognitions and behaviours: a meta
      analysis of the experimental evidence.
AB  - Several reviews suggest that positive affect is associated with improved
      longevity, fewer physical symptoms, and biological indicators of good health. It
      is possible that positive affect could influence these outcomes by promoting
      healthful cognitions and behaviours. The present review identified conceptual
      pathways from positive affect to health cognitions and behaviour, and used random
      effects meta-analysis to quantify the impact of positive affect inductions
      (versus neutral affect conditions) on these outcomes. Literature searches located
      54 independent tests that could be included in the review. Across all studies,
      the findings revealed no reliable effects on intentions (d+ = -.12, 95% CI = -.32
      to .08, k = 15) or behaviour (d+ = .15, 95% CI = -.03 to .33, k = 23). There were
      four reliable effects involving specific cognitions and behaviours, but little
      clear evidence for generalised benefits or adverse effects of positive emotions
      on health-related cognitions or actions. Conclusions must be cautious given the
      paucity of tests available for analysis. The review offers suggestions about
      research designs that might profitably be deployed in future studies, and calls
      for additional tests of the impact of discrete positive emotions on health
      cognitions and behaviour. 

PMID- 27028048
TI  - Carbon Quantum Dot Surface-Engineered VO2 Interwoven Nanowires: A Flexible
      Cathode Material for Lithium and Sodium Ion Batteries.
AB  - The use of electrode materials in their powdery form requires binders and
      conductive additives for the fabrication of the cells, which leads to
      unsatisfactory energy storage performance. Recently, a new strategy to design
      flexible, binder-, and additive-free three-dimensional electrodes with nanoscale
      surface engineering has been exploited in boosting the storage performance of
      electrode materials. In this paper, we design a new type of free-standing carbon
      quantum dot coated VO2 interwoven nanowires through a simple fabrication process
      and demonstrate its potential to be used as cathode material for lithium and
      sodium ion batteries. The versatile carbon quantum dots that are vastly flexible
      for surface engineering serve the function of protecting the nanowire surface and
      play an important role in the diffusion of electrons. Also, the three-dimensional
      carbon cloth coated with VO2 interwoven nanowires assisted in the diffusion of
      ions through the inner and the outer surface. With this unique architecture, the
      carbon quantum dot nanosurface engineered VO2 electrode exhibited capacities of
      420 and 328 mAh g(-1) at current density rate of 0.3 C for lithium and sodium
      storage, respectively. This work serves as a milestone for the potential
      replacement of lithium ion batteries and next generation postbatteries. 

PMID- 27028050
TI  - Cancer and chemotherapy-induced nausea and vomiting: a focus on olanzapine.
AB  - PURPOSE OF THE REVIEW: The purpose of review is to critically present the
      evidence supporting the use of olanzapine, an atypical antipsychotic, as an
      antiemetic for cancer and chemotherapy-induced nausea and vomiting (CINV). RECENT
      FINDINGS: Two phase III clinical studies demonstrated superior efficacy of
      olanzapine in comparison with the neurokinin-1 receptor antagonists (NK1RA) for
      substance P (aprepitant, fosaprepitant) in the prevention of nausea after highly
      emetogenic chemotherapy. Olanzapine is inexpensive and the replacement of NK1RA
      with olanzapine can reduce the costs of the prevention of CINV. The addition of
      olanzapine to aprepitant-containing combination regimens for the prevention of
      CINV was also investigated, and has the potential to further improve the
      prevention of CINV after highly emetogenic chemotherapy or moderately emetogenic
      chemotherapy, without substantial increase in costs. In the treatment of
      uncontrolled ('breakthrough') CINV, olanzapine was more effective than
      metoclopramide. Existing clinical data also support the use of olanzapine to
      relieve a cluster of gastrointestinal symptoms in patients with advanced cancer
      (chronic nausea, vomiting, and anorexia). When used in cancer patients,
      olanzapine is well tolerated, with sedation being the major dose-limiting side
      effect. SUMMARY: Existing data from clinical trials justify further research of
      the role of olanzapine in the prevention of CINV. Olanzapine may be used instead
      of or in addition to NK1RA in the preventive antiemetic regimens. Olanzapine
      containing preventive regimens may provide better nausea control after
      chemotherapy. When used instead of NK1RA it may also provide substantial
      reduction in costs of CINV prevention. In patients with advanced cancer,
      olanzapine was effective against a cluster of gastrointestinal symptoms (nausea,
      vomiting, and anorexia). The use of olanzapine as an antiemetic for CINV, or to
      relieve nausea, vomiting, and anorexia in palliative care is currently off-label.

PMID- 27028051
TI  - Preparation of the Cyclopentazole Anion in the Bulk: A Computational Study.
AB  - The cyclopentazole anion (cyclo-N5(-)), calculated to be a stable species, was
      prepared in the gas phase but attempts to synthesize it in the bulk have so far
      been futile. An aryl pentazole radical anion was suggested as a promising
      precursor in the gas phase. It is shown computationally that the radical anion
      (which may be prepared by reduction of the phenyl pentazole neutral) may indeed
      be used to form the cyclopetazolate anion in the gas phase and in liquid
      solution, alongside and in competition with the extrusion of N2 to produce the
      corresponding azide. In the gas phase, the C-N dissociation yields are very low
      due to much more efficient detachment of an electron. In polar solvents,
      ionization is suppressed and the primary yields of the two competing reactions
      are similar. The reaction must be carried out at low temperatures and special
      measures have to be taken to avoid recombination of the nascent cyclo-N5(-) with
      the geminate phenyl radical. A possible remedy is to use a solvent that reacts
      efficiently with the phenyl radical by H atom transfer.

PMID- 27028052
TI  - A genome-wide association study of copy number variations with umbilical hernia
      in swine.
AB  - Umbilical hernia (UH) is one of the most common congenital defects in pigs,
      leading to considerable economic loss and serious animal welfare problems. To
      test whether copy number variations (CNVs) contribute to pig UH, we performed a
      case-control genome-wide CNV association study on 905 pigs from the Duroc,
      Landrace and Yorkshire breeds using the Porcine SNP60 BeadChip and penncnv
      algorithm. We first constructed a genomic map comprising 6193 CNVs that pertain
      to 737 CNV regions. Then, we identified eight CNVs significantly associated with
      the risk for UH in the three pig breeds. Six of seven significantly associated
      CNVs were validated using quantitative real-time PCR. Notably, a rare CNV
      (CNV14:13030843-13059455) encompassing the NUGGC gene was strongly associated
      with UH (permutation-corrected P = 0.0015) in Duroc pigs. This CNV occurred
      exclusively in seven Duroc UH-affected individuals. SNPs surrounding the CNV did
      not show association signals, indicating that rare CNVs may play an important
      role in complex pig diseases such as UH. The NUGGC gene has been implicated in
      human omphalocele and inguinal hernia. Our finding supports that CNVs, including
      the NUGGC CNV, contribute to the pathogenesis of pig UH. 

PMID- 27028053
TI  - Predicting Schizophrenia.

PMID- 27028054
TI  - Increase in urinary markers during the acute phase reflects the degree of chronic
      tubulointerstitial injury after ischemia-reperfusion renal injury.
AB  - CONTEXT: Acute kidney injury (AKI) could lead to progressive chronic kidney
      disease (CKD). OBJECTIVES: To demonstrate that urinary markers in AKI are
      associated with the degree of persistent renal injury. MATERIAL AND METHODS:
      Human L-FABP chromosomal transgenic (Tg) mice were subjected to ischemia
      reperfusion (I/R) clamping renal pedicle for 20 min or 30 min. Kidneys were
      obtained at one and 40 days after I/R. RESULTS: Urinary L-FABP, NGAL, Kim-1 and
      albumin levels increased during the acute phase and were significantly correlated
      with the degree of tubulointerstitial fibrosis during the chronic phase.
      DISCUSSION AND CONCLUSION: These markers could detect higher risk of progression
      to CKD.

PMID- 27028055
TI  - Efficient Purification and Release of Circulating Tumor Cells by Synergistic
      Effect of Biomarker and SiO2 @Gel-Microbead-Based Size Difference Amplification.
AB  - Microfluidics-based circulating tumor cell (CTC) isolation is achieved by using
      gelatin-coated silica microbeads conjugated to CTC-specific antibodies. Bead
      binding selectively enlarges target cell size, providing efficient high-purity
      capture. CTCs captured can be further released non-invasively. This stratagem
      enables high-performance CTC isolation for subsequent studies.

PMID- 27028057
TI  - Uniting C1-Ammonium Enolates and Transition Metal Electrophiles via Cooperative
      Catalysis: The Direct Asymmetric alpha-Allylation of Aryl Acetic Acid Esters.
AB  - The direct, catalytic, asymmetric alpha-functionalization of acyclic esters
      constitutes a significant challenge in the area of asymmetric catalysis,
      particularly where the configurational integrity of the products is problematic.
      Through the unprecedented merger of two independent, yet complementary, catalysis
      events it has been possible to facilitate the direct asymmetric alpha-allylation
      of readily available aryl acetic acid esters. Since enantioselection is
      determined by the nucleophile, this conceptual approach to cooperative catalysis
      constitutes a potentially general solution to the direct catalytic asymmetric
      alpha-functionalization of acyclic esters.

PMID- 27028056
TI  - The protective effect of prophylactic ozone administration against retinal
      ischemia-reperfusion injury.
AB  - INTRODUCTION: Retinal ischemia-reperfusion (IR) injury is associated with many
      ocular diseases. Retinal IR injury leads to the death of retinal ganglion cells
      (RGCs), loss of retinal function and ultimately vision loss. The aim of this
      study was to show the protective effects of prophylactic ozone administration
      against retinal IR injury. MATERIALS AND METHODS: A sham group (S) (n = 7) was
      administered physiological saline (PS) intraperitoneally (i.p.) for 7 d. An
      ischemia reperfusion (IR) group (n = 7) was subjected to retinal ischemia
      followed by reperfusion for 2 h. An ozone group (O) (n = 7) was administered 1
      mg/kg of ozone i.p. for 7 d. In the ozone + IR (O + IR) group (n = 7), 1 mg/kg of
      ozone was administered i.p. for 7 d before the IR procedure and at 8 d, the IR
      injury was created (as in IR group). The rats were anesthetized after second hour
      of reperfusion and their intracardiac blood was drawn completely and they were
      sacrificed. Blood samples were sent to a laboratory for analysis of superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total
      oxidant score (TOS) and total antioxidant capacity (TAC). The degree of retinal
      injury was evaluated according to changes in retinal cells and necrotic and
      apoptotic cells using the TUNEL method. Data were evaluated statistically with
      the Kruskal-Wallis test. RESULTS: The number of RGCs and the inner retinal
      thickness were significantly decreased after ischemia, and treatment with ozone
      significantly inhibited retinal ischemic injury. In the IR group, the degree of
      retinal injury was found to be the highest. In the O + IR group, retinal injury
      was found to be decreased in comparison to the IR group. In the ozone group
      without retinal IR injury, the retinal injury score was the lowest. The
      differences in the antioxidant parameters SOD, GSH-Px and TAC were increased in
      the ozone group and the lowest in the IR group. The oxidant parameters MDA and
      TOS were found to be the highest in the IR group and decreased in the ozone
      group. DISCUSSION: IR injury is also positively correlated with the degree of
      early apoptosis. This study demonstrated that ozone can attenuate subsequent
      ischemic damage in the rat retina through triggering the increase of the
      antioxidant capacity.

PMID- 27028058
TI  - [Dengue vaccines. A reality for Argentina?].
AB  - Dengue outbreaks have occurred yearly in Argentina since 1998. A number of
      candidate vaccines have been tested in endemic countries. The most advanced one
      was licensed in three countries of Latin America for children over 9 years of
      age. In the present article the benefits and drawbacks of these vaccines as well
      as the challenges for the implementation of a vaccination strategy in Argentina
      are discussed. Furthermore, a risk stratification strategy with new criteria and
      a multidisciplinary vision is suggested as a possible path for the assessment of
      the pertinence of a vaccination program in areas showing the highest risk of
      dengue transmission and/or for people at the greatest risk of developing severe
      dengue. It is also suggested that the definition regarding the status of
      endemicity should take into account the local realities. Finally, this paper
      proposes a broad discussion on the evidences, the expected impact and
      instrumental aspects that would be involved in the incorporation of a dengue
      vaccine, marketed or in development, into the national immunization program, and
      especially which subpopulation should be targeted for the immunization strategy
      to be cost-effective. 

PMID- 27028059
TI  - "It goes beyond good camaraderie": A qualitative study of the process of becoming
      an interprofessional healthcare "teamlet".
AB  - Within the US, the patient-centred medical home has become a predominant model in
      the delivery of primary care. This model requires a shift from the physician
      centric model to an interprofessional team-based approach. Thus, healthcare staff
      are being reorganized into teams, resulting in having to work and relate to one
      another in new ways. In 2010, the Veterans Health Administration implemented the
      patient aligned care team (PACT) model, its version of the patient-centred
      medical home. The transition to the PACT model involved restructuring primary
      care staff into "teamlets", consisting of a registered nurse, licensed practical
      nurse, and administrative clerk for each full-time-equivalent primary care
      provider. This qualitative study used observation and semi-structured interviews
      to understand the factors that affect teamlet functioning as they implement this
      new model of care and how teams are interacting to address those factors.
      Findings suggest that role understanding includes understanding how each teamlet
      member's tasks are performed in the daily operations of the clinic. In addition,
      willingness to perform tasks that benefit the teamlet and acceptance of
      delegation from all teamlet members were found to be important for teamlet
      functioning and cohesion. In order for healthcare teams to provide patient
      centred care, it is important to provide guidance and support about what these
      new relationships and roles will entail. The building of team relationships is
      not a static process; ways of working together build over time and, therefore,
      should be seen as a continuous cycle of quality improvement. 

PMID- 27028060
TI  - Coevolution between the Human Microbiota and the Epithelial Immune System.
AB  - The composition and spatial distribution of our gut microbiota is tightly
      controlled by the host to prevent bacterial invasion and systemic infection. The
      gastrointestinal epithelium is predominantly made up of a cellular monolayer
      equipped with a number of sophisticated autonomous defense mechanisms, which are
      strikingly efficient in maintaining homeostasis between the luminal microbes and
      the host. This short review highlights aspects of this finetuned interplay. We
      also address how deficiencies in mucosal defense can promote disease. First,
      genetic defects of sensors or effectors of epithelial defense can result in the
      disruption of the mucosal barrier and lead to chronic inflammatory conditions.
      Second, chronic colonizers of the gastrointestinal tract can actively manipulate
      mucosal defense to escape immune surveillance. As shown for Helicobacter pylori
      in the stomach, sustained manipulation of the epithelium through specialized
      virulence determinants can increase the risk for genetic lesions and malignant
      transformation. 

PMID- 27028061
TI  - Ten years of R&D and full automation in molecular diagnosis.
AB  - A 10-year experience of our automated molecular diagnostic platform that carries
      out 91 different real-time PCR is described. Progresses and future perspectives
      in molecular diagnostic microbiology are reviewed: why automation is important;
      how our platform was implemented; how homemade PCRs were developed; the
      advantages/disadvantages of homemade PCRs, including the critical aspects of
      troubleshooting and the need to further reduce the turnaround time for specific
      samples, at least for defined clinical settings such as emergencies. The future
      of molecular diagnosis depends on automation, and in a novel perspective, it is
      time now to fully acknowledge the true contribution of molecular diagnostic and
      to reconsider the indication for PCR, by also using these tests as first-line
      assays. 

PMID- 27028062
TI  - Hyperglycemia Enhances the Production of Amyloid beta1-42 in the Lenses of Otsuka
      Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes.
AB  - PURPOSE: It has been reported that the accumulation of amyloid beta1-42 (Abeta1
      42) in human lenses can cause some forms of lens opacification. However, the
      factors leading to changes in the accumulation of Abeta in the lens remain
      obscure. In this study, we investigate the effect of hyperglycemia on Abeta1-42
      accumulation in lenses. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats
      and the human lens epithelial cell line SRA 01/04 (HLE cells) were used. The
      expression of mRNA was determined using a quantitative real-time RT-PCR method;
      Abeta1-42 levels were analyzed by an ELISA method. RESULTS: Otsuka Long-Evans
      Tokushima Fatty rats at more than 20 weeks of age develop diabetes mellitus with
      hyperglycemia. Additionally, the levels of the mRNAs for Abeta1-42, amyloid
      precursor proteins (APP), beta-(BACE1), and.gamma-secretase (PS) rise in the
      lenses of OLETF rats with age; high Abeta1-42 levels are observed in the lens
      capsule-epithelium and cortex. The enhanced expression of the genes for APP,
      BACE1, and PS in the lenses of OLETF rats is prevented by food restriction (25
      g/d/rat). When the effect of glucose levels on the production of Abeta1-42 was
      investigated in the human lens epithelial cell line SRA 01/04 (HLE cells), the
      mRNA levels for APP, BACE1, and PS, as well as Abeta1-42 protein levels, were
      significantly higher under high glucose conditions (20 mM) than under normal
      glucose conditions (5.6 mM). CONCLUSIONS: High glucose leads to the increased
      expression of genes related to Abeta production, resulting in the accumulation of
      Abeta in the lens.

PMID- 27028064
TI  - Erratum.

PMID- 27028063
TI  - Early Retinal Neuronal Dysfunction in Diabetic Mice: Reduced Light-Evoked
      Inhibition Increases Rod Pathway Signaling.
AB  - PURPOSE: Recent studies suggest that the neural retinal response to light is
      compromised in diabetes. Electroretinogram studies suggest that the dim light
      retinal rod pathway is especially susceptible to diabetic damage. The purpose of
      this study was to determine whether diabetes alters rod pathway signaling.
      METHODS: Diabetes was induced in C57BL/6J mice by three intraperitoneal
      injections of streptozotocin (STZ; 75 mg/kg), and confirmed by blood glucose
      levels > 200 mg/dL. Six weeks after the first injection, whole-cell voltage clamp
      recordings of spontaneous and light-evoked inhibitory postsynaptic currents from
      rod bipolar cells were made in dark-adapted retinal slices. Light-evoked
      excitatory currents from rod bipolar and AII amacrine cells, and spontaneous
      excitatory currents from AII amacrine cells were also measured. Receptor inputs
      were pharmacologically isolated. Immunohistochemistry was performed on whole
      mounted retinas. RESULTS: Rod bipolar cells had reduced light-evoked inhibitory
      input from amacrine cells but no change in excitatory input from rod
      photoreceptors. Reduced light-evoked inhibition, mediated by both GABAA and GABAC
      receptors, increased rod bipolar cell output onto AII amacrine cells. Spontaneous
      release of GABA onto rod bipolar cells was increased, which may limit GABA
      availability for light-evoked release. These physiological changes occurred in
      the absence of retinal cell loss or changes in GABAA receptor expression levels.
      CONCLUSIONS: Our results indicate that early diabetes causes deficits in the rod
      pathway leading to decreased light-evoked rod bipolar cell inhibition and
      increased rod pathway output that provide a basis for the development of early
      diabetic visual deficits.

PMID- 27028065
TI  - Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes
      Severe Retinal Degeneration.
AB  - PURPOSE: Digoxin, a major medication for heart disease, was recently reported to
      have immunosuppressive capacity. Here, we determined the immunosuppressive
      capacity of digoxin on the development of experimental autoimmune uveitis (EAU)
      and on related immune responses. METHODS: The B10.A mice were immunized with
      interphotoreceptor retinoid-binding protein (IRBP) and were treated daily with
      digoxin or vehicle control. On postimmunization day 14, the mouse eyes were
      examined histologically, while spleen cells were tested for cytokine production
      in response to IRBP and purified protein derivative. The immunosuppressive
      activity of digoxin was also tested in vitro, by its capacity to inhibit
      development of Th1 or Th17 cells. To investigate the degenerative effect of
      digoxin on the retina, naive (FVB/N * B10.BR)F1 mice were similarly treated with
      digoxin and tested histologically and by ERG. RESULTS: Treatment with digoxin
      inhibited the development of EAU, as well as the cellular response to IRBP.
      Unexpectedly, treatment with digoxin suppressed the production of interferon
      gamma to a larger extent than the production of interleukin 17. Importantly,
      digoxin treatment induced severe retinal degeneration, determined by histologic
      analysis with thinning across all layers of the retina. Digoxin treatment also
      induced dose-dependent vision loss monitored by ERG on naive mice without
      induction of EAU. CONCLUSIONS: Treatment of mice with digoxin inhibited the
      development of EAU and cellular immune response to IRBP. However, the treatment
      induced severe damage to the retina. Thus, the use of digoxin in humans should be
      avoided due to its toxicity to the retina.

PMID- 27028066
TI  - Perception of Haidinger Brushes in Macular Disease Depends on Macular Pigment
      Density and Visual Acuity.
AB  - PURPOSE: To optimize the perceptibility of Haidinger brushes (HB) and to
      investigate its association with visual acuity and macular pigment density.
      METHODS: In this prospective cross-sectional study, each subject underwent best
      corrected visual acuity (BCVA) testing, funduscopy, and assessment of macular
      pigment optical density (MPOD) using the two-wavelength fundus autofluorescence
      method. Haidinger brush visibility was tested with a rotating linear polarizer
      and a controllable three-color light-emitting diode (LED) panel as light source.
      A simple model of macular pigment absorption was used to predict HB visibility as
      a function of stimulus wavelength and MPOD. RESULTS: All control eyes (n = 92)
      and 34% of the 198 eyes of subjects with macular disease (age-related macular
      degeneration, n = 40; macular telangiectasia type 2, n = 52; Stargardt disease, n
      = 58; other retinal dystrophies, n = 48) perceived HB when an optimized test
      setup (464-nm LED light) was applied. The degree of psychophysical perception and
      the dependency on different wavelengths were in accordance with the absorptance
      model. In eyes of subjects with macular disease, minimum thresholds of MPOD and
      BCVA required for HB perception were identified. Subjects with macular
      telangiectasia type 2 showed lowest values of MPOD and were mostly unable to
      perceive HB despite relatively preserved BCVA. CONCLUSIONS: Macular pigment and a
      relatively preserved foveal function are necessary for the perception of HB.
      Haidinger brushes are usually not perceived by subjects with macular
      telangiectasia type 2, likely due to their characteristic foveal depletion of
      macular pigment.

PMID- 27028067
TI  - Predicting Growth in Word Level Reading Skills in Children With Developmental
      Dyslexia Using an Object Rhyming Functional Neuroimaging Task.
AB  - An object rhyming task that does not require text reading and is suitable for
      younger children was used to predict gains in word level reading skills following
      an intensive 2-year reading intervention for children with developmental
      dyslexia. The task evoked activation in bilateral inferior frontal regions.
      Growth in untimed pseudoword reading was associated with increased pre
      intervention activation of the left inferior frontal gyrus, and growth in timed
      word reading was associated with pre-intervention activation of the left and
      right inferior frontal gyri. These analyses help identify pre-intervention
      factors that facilitate reading skill improvements in children with developmental
      dyslexia.

PMID- 27028068
TI  - Cilia play a role in breaking left-right symmetry of the sea urchin embryo.
AB  - Left-right asymmetry of bilaterian animals is established during early
      development. In mice, frogs and fishes, the ciliated left-right organizer plays
      an essential role in establishing bilateral asymmetry, and leftward flow of
      extracellular fluid generated by ciliary motion results in Nodal activity on the
      left side. However, H(+) /K(+) -ATPase activity is also involved in the
      determination of left-right asymmetry in a variety of animals, and it has been
      thought to be an ancestral mechanism in deuterostomes. In sea urchin, the
      determination of the left-right asymmetry based on H(+) /K(+) -ATPase activity
      was already clarified, but it remains to be uncovered whether ciliary motion is
      involved in the left-right asymmetry of the embryo. Here, we show evidence that
      ciliary motion is involved in the establishment of left-right asymmetry of sea
      urchin embryo. Furthermore, we show that the initial cilia generated on small
      micromeres during the early stage of embryogenesis may be involved in this
      process. These results suggest that the cilia-mediated mechanism for the
      determination of left-right asymmetry may be acquired at the base of the
      deuterostomes. 

PMID- 27028069
TI  - Conservative versus operative treatment for thoracolumbar burst fractures without
      neurologic deficit.
AB  - Thoracolumbar burst fractures account for up to 17% of major spinal fractures.
      Both conservative and operative treatments are widely used in clinical practice
      to manage thoracolumbar burst fractures. Previous studies showed good functional
      results with both treatments, but surgical approach has been associated with
      higher cost and risks of causing unnecessary adverse effects. Searching in
      Epistemonikos database, which is maintained by screening 30 databases, we
      identified 14 systematic reviews including 25 randomized trials. We combined the
      evidence using meta-analysis and generated a summary of findings table following
      the GRADE approach. We concluded that operative treatment may decrease the risk
      of neurologic impairment, but in turn, could increase the risk of general
      complications. It is unclear whether there are differences in pain reduction,
      improvement in function and quality of life, need for subsequent surgery or
      radiographic progression of kyphosis in both groups. 

PMID- 27028070
TI  - Epidemiological Implications of Host Biodiversity and Vector Biology: Key
      Insights from Simple Models.
AB  - Models used to investigate the relationship between biodiversity change and
      vector-borne disease risk often do not explicitly include the vector; they
      instead rely on a frequency-dependent transmission function to represent vector
      dynamics. However, differences between classes of vector (e.g., ticks and
      insects) can cause discrepancies in epidemiological responses to environmental
      change. Using a pair of disease models (mosquito- and tick-borne), we simulated
      substitutive and additive biodiversity change (where noncompetent hosts replaced
      or were added to competent hosts, respectively), while considering different
      relationships between vector and host densities. We found important differences
      between classes of vector, including an increased likelihood of amplified disease
      risk under additive biodiversity change in mosquito models, driven by higher
      vector biting rates. We also draw attention to more general phenomena, such as a
      negative relationship between initial infection prevalence in vectors and
      likelihood of dilution, and the potential for a rise in density of infected
      vectors to occur simultaneously with a decline in proportion of infected hosts.
      This has important implications; the density of infected vectors is the most
      valid metric for primarily zoonotic infections, while the proportion of infected
      hosts is more relevant for infections where humans are a primary host.

PMID- 27028071
TI  - Do Ecological Niche Models Accurately Identify Climatic Determinants of Species
      Ranges?
AB  - Defining species' niches is central to understanding their distributions and is
      thus fundamental to basic ecology and climate change projections. Ecological
      niche models (ENMs) are a key component of making accurate projections and
      include descriptions of the niche in terms of both response curves and rankings
      of variable importance. In this study, we evaluate Maxent's ranking of
      environmental variables based on their importance in delimiting species' range
      boundaries by asking whether these same variables also govern annual recruitment
      based on long-term demographic studies. We found that Maxent-based assessments of
      variable importance in setting range boundaries in the California tiger
      salamander (Ambystoma californiense; CTS) correlate very well with how important
      those variables are in governing ongoing recruitment of CTS at the population
      level. This strong correlation suggests that Maxent's ranking of variable
      importance captures biologically realistic assessments of factors governing
      population persistence. However, this result holds only when Maxent models are
      built using best-practice procedures and variables are ranked based on
      permutation importance. Our study highlights the need for building high-quality
      niche models and provides encouraging evidence that when such models are built,
      they can reflect important aspects of a species' ecology.

PMID- 27028072
TI  - Reproductive Allochrony in Seasonally Sympatric Populations Maintained by
      Differential Response to Photoperiod: Implications for Population Divergence and
      Response to Climate Change.
AB  - Reproductive allochrony presents a potential barrier to gene flow and is common
      in seasonally sympatric migratory and sedentary birds. Mechanisms mediating
      reproductive allochrony can influence population divergence and the capacity of
      populations to respond to environmental change. We asked whether reproductive
      allochrony in seasonally sympatric birds results from a difference in response to
      supplementary or photoperiodic cues and whether the response varies in relation
      to the distance separating breeding and wintering locations as measured by stable
      isotopes. We held seasonally sympatric migratory and sedentary male dark-eyed
      juncos (Junco hyemalis) in a common garden in early spring under simulated
      natural changes in photoperiod and made measurements of reproductive and
      migratory physiology. On the same dates and photoperiods, sedentary juncos had
      higher testosterone (initial and gonadotropin-releasing hormone induced), more
      developed cloacal protuberances, and larger testes than migrants. In contrast,
      migratory juncos had larger fat reserves (fuel for migration). We found a
      negative relationship between testis mass and feather hydrogen isotope ratios,
      indicating that testis growth was more delayed in migrants making longer
      migrations. We conclude that reproductive allochrony in seasonally sympatric
      migratory and sedentary birds can result from a differential response to
      photoperiodic cues in a common garden, and as a result, gene flow between
      migrants and residents may be reduced by photoperiodic control of reproductive
      development. Further, earlier breeding in response to future climate change may
      currently be constrained by differential response to photoperiodic cues.

PMID- 27028073
TI  - Experimental Evidence for an Eco-Evolutionary Coupling between Local Adaptation
      and Intraspecific Competition.
AB  - Determining how adaptive evolution can be coupled to ecological processes is key
      for developing a more integrative understanding of the demographic factors that
      regulate populations. Intraspecific competition is an especially important
      ecological process because it generates negative density dependence in
      demographic rates. Although ecological factors are most often investigated to
      determine the strength of density dependence, evolutionary processes such as
      local adaptation could also feed back to shape variation in the strength of
      density dependence among populations. Using an experimental approach with
      damselflies, a predaceous aquatic insect, we find evidence that both density
      dependent intraspecific competition and local adaptation can reduce per capita
      growth rates. In some cases, the effects of local adaptation on reducing per
      capita growth rates exceeded the ecological competitive effects of a doubling of
      density. However, we also found that these ecological and evolutionary properties
      of populations are coupled, and we offer two interpretations of the causes
      underlying this pattern: (1) the strength of density-dependent competition
      depends on the extent of local adaptation, or (2) the extent of local adaptation
      is shaped by the strength of density-dependent competition. Regardless of the
      underlying causal pathway, these results show how eco-evolutionary dynamics can
      affect a key demographic process regulating populations.

PMID- 27028074
TI  - Estimating Effects of Species Interactions on Populations of Endangered Species.
AB  - Global change causes community composition to change considerably through time,
      with ever-new combinations of interacting species. To study the consequences of
      newly established species interactions, one available source of data could be
      observational surveys from biodiversity monitoring. However, approaches using
      observational data would need to account for niche differences between species
      and for imperfect detection of individuals. To estimate population sizes of
      interacting species, we extended N-mixture models that were developed to estimate
      true population sizes in single species. Simulations revealed that our model is
      able to disentangle direct effects of dominant on subordinate species from
      indirect effects of dominant species on detection probability of subordinate
      species. For illustration, we applied our model to data from a Swiss amphibian
      monitoring program and showed that sizes of expanding water frog populations were
      negatively related to population sizes of endangered yellow-bellied toads and
      common midwife toads and partly of natterjack toads. Unlike other studies that
      analyzed presence and absence of species, our model suggests that the spread of
      water frogs in Central Europe is one of the reasons for the decline of endangered
      toad species. Thus, studying population impacts of dominant species on population
      sizes of endangered species using data from biodiversity monitoring programs
      should help to inform conservation policy and to decide whether competing species
      should be subject to population management.

PMID- 27028075
TI  - Interaction between Digestive Strategy and Niche Specialization Predicts
      Speciation Rates across Herbivorous Mammals.
AB  - Biotic and abiotic factors often are treated as mutually exclusive drivers of
      diversification processes. In this framework, ecological specialists are expected
      to have higher speciation rates than generalists if abiotic factors are the
      primary controls on species diversity but lower rates if biotic interactions are
      more important. Speciation rate is therefore predicted to positively correlate
      with ecological specialization in the purely abiotic model but negatively
      correlate in the biotic model. In this study, I show that the positive
      relationship between ecological specialization and speciation expected from the
      purely abiotic model is recovered only when a species-specific trait, digestive
      strategy, is modeled in the terrestrial, herbivorous mammals (Mammalia). This
      result suggests a more nuanced model in which the response of specialized
      lineages to abiotic factors is dependent on a biological trait. I also
      demonstrate that the effect of digestive strategy on the ecological
      specialization-speciation rate relationship is not due to a difference in either
      the degree of ecological specialization or the speciation rate between foregut-
      and hindgut-fermenting mammals. Together, these findings suggest that a
      biological trait, alongside historical abiotic events, played an important role
      in shaping mammal speciation at long temporal and large geographic scales.

PMID- 27028076
TI  - A Random Walk in the Park: An Individual-Based Null Model for Behavioral
      Thermoregulation.
AB  - Behavioral thermoregulators leverage environmental temperature to control their
      body temperature. Habitat thermal quality therefore dictates the difficulty and
      necessity of precise thermoregulation, and the quality of behavioral
      thermoregulation in turn impacts organism fitness via the thermal dependence of
      performance. Comparing the body temperature of a thermoregulator with a null (non
      thermoregulating) model allows us to estimate habitat thermal quality and the
      effect of behavioral thermoregulation on body temperature. We define a null model
      for behavioral thermoregulation that is a random walk in a temporally and
      spatially explicit thermal landscape. Predicted body temperature is also
      integrated through time, so recent body temperature history, environmental
      temperature, and movement influence current body temperature; there is no
      particular reliance on an organism's equilibrium temperature. We develop a metric
      called thermal benefit that equates body temperature to thermally dependent
      performance as a proxy for fitness. We measure thermal quality of two distinct
      tropical habitats as a temporally dynamic distribution that is an ergodic
      property of many random walks, and we compare it with the thermal benefit of real
      lizards in both habitats. Our simple model focuses on transient body temperature;
      as such, using it we observe such subtleties as shifts in the thermoregulatory
      effort and investment of lizards throughout the day, from thermoregulators to
      thermoconformers.

PMID- 27028077
TI  - Migratory Recovery from Infection as a Selective Pressure for the Evolution of
      Migration.
AB  - Migration, a widespread animal behavior, can influence how individuals acquire
      and transmit pathogens. Past work has demonstrated that migration can reduce the
      costs of pathogen or parasite infection through two processes: migratory escape
      from infected areas or individuals and migratory culling of infected individuals.
      Here, we propose a third process: migratory recovery, where infected individuals
      lose their parasites and recover from infection during migration. Recovery can
      occur when parasites and/or their intermediate hosts cannot support changes in
      the migratory host's internal or external environment during migration. Thus,
      parasite mortality increases with migration. Although migratory recovery is
      likely widespread across species, it remains challenging to empirically test it
      as a selective force promoting migration. We develop a model and determine the
      conditions under which migratory recovery theoretically favors the evolution of
      migration. We show that incorporating migratory recovery into a model of
      migratory escape increases the range of biologically realistic conditions
      favoring migration and leads to scenarios where partial migration can evolve.
      Motivated by empirical estimates of infection costs, our model shows how recovery
      from infection could drive the evolution of migration. We suggest a number of
      future directions for both theoretical and empirical research in this area.

PMID- 27028078
TI  - Abundance Inequality in Freshwater Communities Has an Ecological Origin.
AB  - The hollow-shaped species abundance distribution (SAD) and its allied rank
      abundance distribution (RAD)-showing that abundance is unevenly distributed among
      species-are some of the most studied patterns in ecology. To explain the nature
      of abundance inequality, I developed a novel framework identifying environmental
      favorability, which controls the balance between reproduction and immigration, as
      the ultimate source and species stress tolerance as a proximate factor. Thus,
      under harsh conditions, only a few tolerant species can reproduce, while some
      sensitive species can be present in low numbers due to chance immigration. This
      would lead to high abundance inequality between the two groups of species. Under
      benign conditions, both groups can reproduce and give rise to higher abundance
      equality. To test these ideas, I examined the variability in the parameters of a
      Poisson lognormal fit of the SAD and a square root fit of the RAD in diatom and
      fish communities across US streams. Indeed, as environmental favorability
      increased, more sensitive forms were able to establish large populations,
      diminishing the abundance disparity between locally common and rare species.
      Finally, it was demonstrated that in diatoms, the RAD belonged to the same family
      of relationships as those of population density with body size and regional
      distribution.

PMID- 27028079
TI  - Mating System Transitions Drive Life Span Evolution in Pristionchus Nematodes.
AB  - Interactions between the sexes influence evolution at many scales, but not all
      animal species conform to the familiar male-female (dioecious) mating system;
      such taxa are powerful tools for studying the evolutionary importance of sexual
      selection and conflict on all manner of life-history traits, including longevity.
      We tested for an effect of mating system on adult life span in Pristionchus
      nematodes, where self-fertile hermaphrodites have replaced females multiple times
      independently throughout the genus (androdioecy). By measuring adult life span
      for 11 species (6 dioecious, 5 androdioecious), we found that life span is
      considerably shorter in hermaphrodites relative to closely related females. This
      effect is not a cost of reproduction; brood size did not reliably trade off with
      life span in self-fertilizing hermaphrodites or in mated females. Furthermore, we
      found that sexual dimorphism in life span varied among dioecious species, with
      females generally outliving males. Finally, we documented intraspecific variation
      for life span and cuticular disease (blistering) prevalence in Pristionchus
      pacificus, a model system for evolutionary-developmental biology. This work
      demonstrates that mating system transitions and life span evolution are linked in
      Pristionchus nematodes and provides a foundation for future comparative and
      mechanistic studies of aging in this genus.

PMID- 27028080
TI  - Sex-Specific Arrival Times on the Breeding Grounds: Hybridizing Migratory Skuas
      Provide Empirical Support for the Role of Sex Ratios.
AB  - In migratory animals, protandry (earlier arrival of males on the breeding
      grounds) prevails over protogyny (females preceding males). In theory, sex
      differences in timing of arrival should be driven by the operational sex ratio,
      shifting toward protogyny in female-biased populations. However, empirical
      support for this hypothesis is, to date, lacking. To test this hypothesis, we
      analyzed arrival data from three populations of the long-distance migratory south
      polar skua (Catharacta maccormicki). These populations differed in their
      operational sex ratio caused by the unidirectional hybridization of male south
      polar skuas with female brown skuas (Catharacta antarctica lonnbergi). We found
      that arrival times were protandrous in allopatry, shifting toward protogyny in
      female-biased populations when breeding in sympatry. This unique observation is
      consistent with theoretical predictions that sex-specific arrival times should be
      influenced by sex ratio and that protogyny should be observed in populations with
      female-biased operational sex ratio.

PMID- 27028081
TI  - When to Reproduce? A New Answer to an Old Question.
AB  - We present a life-history model based on the assumptions that juvenile survival
      follows a negative exponential function and that fecundity gain increases
      linearly with time to maturity. This model predicts that the optimal fitness is
      achieved when survival at maturity is 0.368 (e(-1)). Survival at the time of
      maturity is therefore an invariant. We tested this prediction by using published
      data from infection experiments with mammalian nematodes, where both the initial
      number of juveniles colonizing a habitat (host) and the numbers surviving at the
      time of maturation were known. We found that the mean survival at maturity, both
      across and within species, was remarkably close to our predicted mean. As a
      control, we also looked at studies where the parasite species was adapted to a
      host species other than the one used in the reported experiment. In these
      experiments the mean survival at maturity differed from what our model predicted.
      Maturation at a fixed survival probability therefore appears as an adaptive trait
      evolved in a predictable environment, in this case, a host species. Our result
      further suggests that measures designed to increase juvenile parasite mortality,
      such as drugs or vaccines, will select for faster developmental rates.

PMID- 27028082
TI  - Intragenomic Conflict over Soldier Allocation in Polyembryonic Parasitoid Wasps.
AB  - Understanding the selection pressures that have driven the evolution of sterile
      insect castes has been the focus of decades of intense scientific debate. An
      amenable empirical test bed for theory on this topic is provided by the sterile
      soldier caste of polyembryonic parasitoid wasps. The function of these soldiers
      has been a source of controversy, with two basic hypotheses emerging: the "brood
      benefit" hypothesis that they provide an overall benefit for their siblings and
      the "sex-ratio-conflict" hypothesis that the soldiers mediate a conflict between
      brothers and sisters by killing their opposite-sex siblings. Here, we investigate
      the divergent sex-ratio optima of a female embryo's maternal-origin and paternal
      origin genes, to determine the potential for, and direction of, intragenomic
      conflict over soldiering. We then derive contrasting empirically testable
      predictions concerning the patterns of genomic imprinting that are expected to
      arise out of this intragenomic conflict, for the brood-benefit versus the sex
      ratio-conflict hypothesis of soldier function.

PMID- 27028083
TI  - Constancy in Functional Space across a Species Richness Anomaly.
AB  - The relationship between large-scale gradients in species richness and functional
      diversity provides important information regarding the mechanisms driving
      patterns of biodiversity. A classic hypothesis in ecology is that strong
      interspecific interactions should result in an increase in the functional volume
      of assemblages as the species richness increases, whereas climatic constraints
      may result in no change in functional volume. Most research of this kind examines
      latitudinal gradients in species richness, but the results are likely confounded
      by underlying gradients in climate and phylogenetic composition. We take an
      alternative approach that examines functional richness across a tree species
      richness anomaly where species richness doubles from Europe to eastern North
      America. The results demonstrate that the functional richness on both continents
      saturates at a similar point as species richness increases and that the packing
      of functional space becomes tighter. Further, the species richness anomaly is
      driven primarily by genera unique to North America, but those genera contribute
      less than expected functional richness to the region, indicating a high level of
      redundancy with genera shared between the continents. Taken together, the results
      indicate that the species richness anomaly is associated with diversification
      within a climatically constrained trait space. More generally, the work
      demonstrates the power of utilizing species richness anomalies in biodiversity
      research, particularly when they are coupled with information regarding
      organismal function.

PMID- 27028084
TI  - Do Hypervolumes Have Holes?
AB  - Hypervolumes are used widely to conceptualize niches and trait distributions for
      both species and communities. Some hypervolumes are expected to be convex, with
      boundaries defined by only upper and lower limits (e.g., fundamental niches),
      while others are expected to be maximal, with boundaries defined by the limits of
      available space (e.g., potential niches). However, observed hypervolumes (e.g.,
      realized niches) could also have holes, defined as unoccupied hyperspace
      representing deviations from these expectations that may indicate unconsidered
      ecological or evolutionary processes. Detecting holes in more than two dimensions
      has to date not been possible. I develop a mathematical approach, implemented in
      the hypervolume R package, to infer holes in large and high-dimensional data
      sets. As a demonstration analysis, I assess evidence for vacant niches in a
      Galapagos finch community on Isabela Island. These mathematical concepts and
      software tools for detecting holes provide approaches for addressing contemporary
      research questions across ecology and evolutionary biology.

PMID- 27028085
TI  - Invisible Trade-offs: Van Noordwijk and de Jong and Life-History Evolution.

PMID- 27028086
TI  - Predicting the lifetime of organic vapor cartridges exposed to volatile organic
      compound mixtures using a partial differential equations model.
AB  - In this study, equilibria, breakthrough curves, and breakthrough times were
      predicted for three binary mixtures of four volatile organic compounds (VOCs)
      using a model based on partial differential equations of dynamic adsorption
      coupling a mass balance, a simple Linear Driving Force (LDF) hypothesis to
      describe the kinetics, and the well-known Extended-Langmuir (EL) equilibrium
      model. The model aims to predict with a limited complexity, the BTCs of
      respirator cartridges exposed to binary vapor mixtures from equilibria and
      kinetics data obtained from single component. In the model, multicomponent mass
      transfer was simplified to use only single dynamic adsorption data. The EL
      expression used in this study predicted equilibria with relatively good accuracy
      for acetone/ethanol and ethanol/cyclohexane mixtures, but the prediction of
      cyclohexane uptake when mixed with heptane is less satisfactory. The BTCs given
      by the model were compared to experimental BTCs to determine the accuracy of the
      model and the impact of the approximation on mass transfer coefficients. From
      BTCs, breakthrough times at 10% of the exposure concentration t10% were
      determined. All t10% were predicted within 20% of the experimental values, and
      63% of the breakthrough times were predicted within a 10% error. This study
      demonstrated that a simple mass balance combined with kinetic approximations is
      sufficient to predict lifetime for respirator cartridges exposed to VOC mixtures.
      It also showed that a commonly adopted approach to describe multicomponent
      adsorption based on volatility of VOC rather than adsorption equilibrium greatly
      overestimated the breakthrough times.

PMID- 27028087
TI  - Male genital dermatophytosis - clinical features and the effects of the misuse of
      topical steroids and steroid combinations - an alarming problem in India.
AB  - Genital dermatophytosis has been considered rare by most Western authorities.
      However, to the contrary, Indian reports have shown a higher prevalence of
      genital dermatophytosis due to warm and humid climate, overcrowding and lack of
      hygiene. A review is presented for 24 cases of male genital dermatophytosis
      occurring in patients suffering from tinea cruris in India who have been randomly
      applying various broad-spectrum steroid antifungal and antibacterial creams
      containing one or more antifungal and antibiotic in addition to potent
      corticosteroids, mainly clobetasol propionate. This is such a common phenomenon
      that Indian dermatologists are witnessing an epidemic of sorts of steroid
      modified dermatophytosis and we hereby share various clinical presentations of
      dermatophytosis of penis and/or scrotum in patients with tinea cruris who have
      been applying the above-mentioned creams. The review also discusses the bleak
      scenario that prevails in India regarding the drug regulatory affairs that allow
      such dangerous and irrational combinations that are sold over the counter because
      of misinterpretation of the law and lax implementation of existing laws. 

PMID- 27028088
TI  - Classification of MALDI-MS imaging data of tissue microarrays using canonical
      correlation analysis-based variable selection.
AB  - Applying MALDI-MS imaging to tissue microarrays (TMAs) provides access to
      proteomics data from large cohorts of patients in a cost- and time-efficient way,
      and opens the potential for applying this technology in clinical diagnosis. The
      complexity of these TMA data-high-dimensional low sample size-provides challenges
      for the statistical analysis, as classical methods typically require a
      nonsingular covariance matrix that cannot be satisfied if the dimension is
      greater than the sample size. We use TMAs to collect data from endometrial
      primary carcinomas from 43 patients. Each patient has a lymph node metastasis
      (LNM) status of positive or negative, which we predict on the basis of the MALDI
      MS imaging TMA data. We propose a variable selection approach based on canonical
      correlation analysis that explicitly uses the LNM information. We apply LDA to
      the selected variables only. Our method misclassifies 2.3-20.9% of patients by
      leave-one-out cross-validation and strongly outperforms LDA after reduction of
      the original data with principle component analysis.

PMID- 27028089
TI  - Poly(ADP-ribose) polymerase-1 silences retroviruses independently of viral DNA
      integration or heterochromatin formation.
AB  - PARP-1 silences retrotransposons in Drosophila, through heterochromatin
      maintenance, and integrated retroviruses in chicken. Here, we determined the role
      of viral DNA integration and cellular heterochromatin in PARP-1-mediated
      retroviral silencing using HIV-1-derived lentiviral vectors and Rous-associated
      virus type 1 (RAV-1) as models. Analysis of the infection of PARP-1 knockout and
      control cells with HIV-1 harbouring WT integrase, in the presence or absence of
      an integrase inhibitor, or catalytic-dead mutant integrase indicated that
      silencing does not require viral DNA integration. The mechanism involves the
      catalytic activity of histone deacetylases but not that of PARP-1. In contrast to
      Drosophila, lack of PARP-1 in avian cells did not affect chromatin compaction
      globally or at the RAV-1 provirus, or the cellular levels of histone H3 N
      terminal acetylated or Lys27 trimethylated, as indicated by micrococcal nuclease
      accessibility and immunoblot assays. Therefore, PARP-1 represses retroviruses
      prior to viral DNA integration by mechanisms involving histone deacetylases but
      not heterochromatin formation.

PMID- 27028090
TI  - Prevalence and predictors of anxiety and depression after completion of
      chemotherapy for childhood acute lymphoblastic leukemia: A prospective
      longitudinal study.
AB  - BACKGROUND: The months immediately after the completion of treatment for
      childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful
      time for children and families. In this prospective, longitudinal study, the
      prevalence and predictors of anxiety and depressive symptoms after the completion
      of treatment were examined. METHODS: Participants included 160 children aged 2 to
      9 years with standard-risk ALL who were enrolled on Children's Oncology Group
      protocol AALL0331. Parents completed standardized rating scales of their
      children's emotional-behavioral functioning and measures of coping and family
      functioning at approximately 1 month, 6 months, and 12 months after diagnosis and
      again 3 months after the completion of chemotherapy. RESULTS: At 3 months off
      therapy, approximately 24% of survivors had at-risk/clinically elevated anxiety
      scores and 28% had elevated depression scores, which are significantly higher
      than the expected 15% in the general population (P = .028 and .001,
      respectively). Patients with elevated anxiety 1 month after diagnosis were at
      greater risk of off-therapy anxiety (odds ratio, 4.1; 95% confidence interval,
      1.31-12.73 [P = .022]) and those with elevated depressive symptoms 6 months after
      diagnosis were at greater risk of off-therapy depression (odds ratio, 7.88; 95%
      confidence interval, 2.61-23.81 [P = .0002]). In adjusted longitudinal analyses,
      unhealthy family functioning (P = .008) and less reliance on social support
      coping (P = .009) were found to be associated with risk of emotional distress.
      Children from Spanish-speaking families (P = .05) also were found to be at a
      greater risk of distress. CONCLUSIONS: A significant percentage of children
      experience emotional distress during and after therapy for ALL. These data
      provide a compelling rationale for targeted early screening and psychosocial
      interventions to support family functioning and coping skills. Cancer
      2016;122:1608-17. (c) 2015 American Cancer Society.

PMID- 27028091
TI  - Comparison of ventricular drain location and infusion test in hydrocephalus.
AB  - OBJECTIVES: Suspected cerebrospinal fluid shunt (CSF) dysfunction in
      hydrocephalic patients poses a diagnostic uncertainty. The clinical picture can
      be non-specific and CT imaging alone is not always pathognomonic. Infusion tests
      are an increasingly used investigation for real-time hydrodynamic assessment of
      shunt patency. We report the correlation between infusion test results with the
      quality of ventricular drain placement on CT scans in a large retrospective group
      of hydrocephalic patients. MATERIALS & METHODS: Three hundred and six infusion
      test results performed in 200 patients were correlated with 306 corresponding CT
      head scans. Nominal logistic regression was used to correlate shunt catheter
      position on CT imaging to patency of ventricular drain as determined by infusion
      tests. RESULTS: Infusion test results of shunt patency are statistically
      congruent with the analysis of shunt catheter position on CT head scans. Catheter
      tips completely surrounded by either parenchyma or CSF on CT imaging are strongly
      associated with evidence of occlusion or patency from infusion tests,
      respectively (chi2 = 51.68, P < 0.0001, n = 306 and chi2 = 31.04, P < 0.0001, n =
      306). CONCLUSIONS: The most important anatomical factor for shunt patency is the
      catheter tip being completely surrounded by CSF. Infusion tests provide
      functional and reliable assessment of shunt patency in vivo and are strongly
      correlated with the position of the ventricular catheter on CT imaging.

PMID- 27028092
TI  - Measuring the Effect of Improved Medical Facilities and Focused Training on Data
      Quality and Completeness: An Example from the Gharbiah Population-Based Cancer
      Registry, Egypt.
AB  - Cancer rates are increasing in low- and middle- income countries. There are a
      limited number of populationbased cancer registries in Africa and the Egyptian
      population-based registry in Gharbiah is one of those registries. This registry
      has followed the standard international registration process and methods since
      1999 and has been included in Cancer Incidence in Five Continents volumes IX and
      X. This article illustrates the reflection of improving medical care in the
      geographic region of the registry and focused training on enhancing the registry
      data. The registry area has seen advancement in medical care and cancer
      diagnostic facilities during the study period. The focused training included 8
      different international training sessions over 8 different years for the
      registrars, administrators, and directors as well as continuing on-the-job
      training for other registry personnel. These improvements resulted in an overall
      40% increase in nonmicroscopic diagnosis of hepatocellular carcinoma, as well as
      20%, 10%, and 10% increases in microscopic diagnosis of pancreatic, brain, and
      lung cancers, respectively, over 9 years. An overall increase of 5% to 10% in
      subsite diagnosis was also seen for lung, colon, brain, bladder, and breast
      cancers for the same 9 years. An increase of 3% in grading was seen for solid
      tumors while 11% was seen for lymphoma. This study showed that low- and middle-
      income countries can observe higher data quality for cancer registries with
      improvement in medical care and focused training. 

PMID- 27028093
TI  - Improving the Completeness of Ascertainment in Florida's Birth Defects
      Surveillance Program: The Impact of Adding Infant Death and Emergency Department
      Data.
AB  - INTRODUCTION: The Florida Birth Defects Registry (FBDR) relies predominantly on a
      statewide, population-based, passive surveillance system constructed by linking
      together multiple administrative and clinical databases. With funding limitations
      and data restrictions a reality in public health, it is imperative for disease
      registries to have ongoing evaluation of existing and new data sources. This
      study quantifies the impact of expanding the FBDR case ascertainment net to
      include infant death certificates (IDCs) and emergency department (ED) discharge
      data on the reported prevalence of birth defects. METHODS: Between 2008 and 2011,
      the FBDR identified cases using various data sources: inpatient and outpatient
      discharge data (2008-2011), Regional Perinatal Intensive Care Center data (2008),
      Early Steps program data (2008), IDCs (2009-2011), and ED data (2010-2011). Using
      hypothetical reconstructions of the FBDR, we examined the overall and unique
      contribution of each data source in identifying infants with birth defects. This
      permitted evaluation of a changing FBDR data source mix during the 4-year study
      period. The effect of adding both IDCs and ED data was investigated by
      constructing the 2010-2011 FBDR with and without these data sources, and then
      comparing frequencies and prevalence rates across each scenario. Analyses were
      conducted for all FBDR cases and for specific birth defect categories;
      improvements in ascertainment were assessed across sociodemographic and perinatal
      characteristics. RESULTS: Overall, IDCs captured 3.4% of all infants with at
      least 1 birth defect studied, ED data captured 3.9% of the cases, and together
      the 2 data sources captured 7.2%. However, IDCs uniquely identified 0.8% of all
      cases, ED data uniquely identified 0.7% of all cases, and collectively they
      identified only 1.4% of cases that would otherwise have been missed. The unique
      contribution of IDC and ED data to case identification varied by defect and
      across sociodemographic and perinatal subgroups, with the largest impact among
      infants with anencephalus (64.7%), trisomy 13 (52.0%), trisomy 18 (22.2%), and
      encephalocele (13.3%), or those who were born weighing less than 1,500 grams or
      less than 32 weeks' gestation, or whose mothers' education was eighth grade or
      less. DISCUSSION: Although their unique contribution is small when all defects
      are considered together, IDCs and ED data contribute cases that would otherwise
      have been disproportionately lost and are thus an important addition to
      surveillance activities. The FBDR continues to strive to create a comprehensive,
      accurate, and efficient statewide birth defects surveillance system.

PMID- 27028094
TI  - Coding of Central Cancer Registry Industry and Occupation Information: The Texas
      and Louisiana Experiences.
AB  - BACKGROUND: Usual industry and occupation text information have been collected by
      central cancer registries but few have had the resources to code these data,
      limiting their usefulness for assessing occupational cancer risks. STUDY AIMS:
      This project was undertaken to use software available from the National Institute
      for Occupational Safety and Health (NIOSH) to code industry and occupation
      information in cancer records reported to the Texas Cancer Registry (TCR) and the
      Louisiana Tumor Registry (LTR) and to assess the feasibility of its use in
      ongoing registry operations; to assess the quality of the reported information;
      and to determine its usefulness in occupational cancer research. METHODS: De
      identified data files of TCR (n = 103,276) and LTR (n = 26,090) cancer records
      were obtained for diagnosis years 2010 and 2011, respectively, for cases aged 14
      years and older, with industry and occupation text. These data fields were coded
      to the 2000 US Census Bureau using the NIOSH Industry and Occupation Computerized
      Coding System (NIOCCS) software at the high level confidence (90% or greater
      accuracy) and through manual code assignments for records not coded by NIOCCS.
      RESULTS: NIOCCS assigned a code for 37.2% of TCR records and 59.9% of LTR
      records. Examination of the quality of the coded data found 44.2% of TCR records
      and 31.1% of LTR records to have missing, unknown, or otherwise insufficient text
      for assigning a specific industry and occupation code. Additionally, the vague
      noninformative category of "retired" was reported for 14.9% and 11.2% of TCR and
      LTR records, respectively. Records with "homemaker/housewife" or those with terms
      indicating that they never worked represented 7.2% of TCR cases and 9.7% of LTR
      cases. Excluding the unknown, never worked, and retired categories, no one
      specific industry or occupation major grouping represented more than 5% of cases
      in either of the registries. CONCLUSION: NIOCCS is a helpful tool for coding
      industry and occupation text and continues to improve, but other registry
      resources are required for implementation into ongoing operations. Improvement in
      data quality of reported text information in cancer records is paramount to
      maximize the efficiency of NIOCCS and improve the availability of coded, specific
      industry and occupation information for occupational cancer research.

PMID- 27028095
TI  - Neuropsychiatric Predictors of Post-Injury Headache After Mild-Moderate Traumatic
      Brain Injury in Veterans.
AB  - OBJECTIVES: To determine differences in neuropsychiatric complaints between
      Veterans with mild to moderate traumatic brain injury (TBI), with and without
      headache, compared with Veteran controls, and to identify neuropsychiatric
      predictors of headache severity. BACKGROUND: Mild to moderate TBI is a common
      occurrence in Veterans, and is frequently associated with complaints of headache.
      Neuropsychiatric complaints are also common among individuals who have sustained
      head injury, although the relationship between these factors and headache after
      injury is unclear. Research is needed to comprehensively determine differences
      between individuals with mild to moderate traumatic brain injury who differ with
      respect to headache, and which injury, psychological, or sleep and fatigue
      factors predict headache severity. METHODS: A cross-sectional study compared 85
      Veterans in three groups (positive for TBI and headache, positive for TBI without
      significant headache, and a control group) on a set of injury characteristics and
      neuropsychiatric variables. Correlates of headache severity were examined, and a
      regression model was used to identify significant independent predictors of
      headache severity. RESULTS: Individuals with mild to moderate TBI and headache
      endorsed significantly greater neuropsychiatric symptoms than participants in the
      other groups (eta(p)2  = .23-.36) Neuropsychiatric complaints, as well as
      presence of posttraumatic amnesia, were correlated with headache in the subsample
      with TBI (rs = .44-.57). When entering all predictors into a regression model,
      only fatigue represented a significant independent predictor of headache severity
      (beta = .59, R2 = .35). CONCLUSIONS: Rather than being a global risk factor, mild
      to moderate TBI was associated with poorer mental health outcomes, particularly
      for those who endorse headache. Findings underscore the possibility that Veterans
      with history of TBI who present with complaints of headache may represent a
      particularly vulnerable subgroup. Additionally, our findings suggest that
      clinical outcomes may be improved in those with neurotrauma by incorporating a
      focus on fatigue in treatment.

PMID- 27028096
TI  - Empowering Change Agents in Hierarchical Organizations: Participatory Action
      Research in Prisons.
AB  - Participatory action research (PAR) approaches harness collaborative partnerships
      to stimulate change in defined communities. The purpose of this article is to
      illustrate key methodological strategies used in the application of PAR methods
      in the particularly challenging environment of a hierarchical organization. A
      study designed to promote sustainable, insider-generated system-level changes in
      the provision of end-of-life (EOL) care in the restrictive setting of six state
      prisons is used as an exemplar of the application of three cardinal principles of
      PAR. First, development of a collaborative network with active partnership
      between outsider academic researchers and insider co-researchers began with
      careful attention to understanding the culture and processes of prisons and
      gaining the support of organizational leadership, using qualitative data
      gathering and trust-building. During the implementation phase, promoting co
      ownership of change in EOL care through the co-construction of knowledge and
      systems to enhance sustainable change required carefully-orchestrated strategies
      to maximize the collaborative spirit of the project. Co-researchers were
      empowered to examine their worlds and capture opportunities for change using new
      leadership skills role-modeled by the research team. Third, their local knowledge
      of the barriers inherent in the contextual reality of prisons was translated into
      achievable system change by production of a toolkit of formalized and well
      rehearsed change strategies that collaborative teams were empowered to enact
      within their hierarchical prison environment. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028097
TI  - The relation between ischemia modified albumin levels and carotid intima media
      thickness in patients with rheumatoid arthritis.
AB  - BACKGROUND: Cardiovascular diseases, among which atherosclerotic heart disease,
      are known to be one of the most important mortality and morbidity causes in
      patients with rheumatoid arthritis (RA). Ischemia modified albumin (IMA) is a
      potential marker that can be used to assess atherosclerosis-related myocardial
      ischemia. Another frequently used marker for the assessment of atherosclerotic
      lesions is the carotid intima media thickness (CIMT). AIM: To evaluate the role
      that IMA has on atherosclerosis development and its clinical usability in
      patients with RA, by assessing the values of IMA and CIMT. METHODS AND MATERIALS:
      Our prospective study was conducted between June 2012 and March 2013 at the
      Rheumatology Department of Necmettin Erbakan Meram Medical School, Turkey. Fifty
      two RA patients, diagnosed according to the 1987 criteria of the American College
      of Rheumatology, and an age- and sex-matched control group of 46 healthy subjects
      were included in this study. RESULTS: No significant difference was detected
      between the groups with respect to age, sex and body mass index. In the patient
      group the IMA and CIMT values were found to be 0.37 +/- 0.12 absorbance units
      (ABSU) and 0.80 +/- 0.22 mm, respectively, while in the control group they were
      0.31 +/- 0.11 ABSU and 0.51 +/- 0.18 mm, respectively. The IMA and CIMT values
      were significantly higher in the patient group (P = 0.022 and P < 0.0001,
      respectively). A positive correlation was found between IMA, CIMT and Disease
      Activity Score of 28 joints (P = 0.016 and P = 0.002, respectively). CONCLUSION:
      Since the values of IMA were higher in the patient group compared to controls and
      because of its correlation with CIMT, we suggest the use of IMA as an early
      marker of atherosclerosis in RA patients.

PMID- 27028098
TI  - Record linkage is feasible with non-identifiable trauma and rehabilitation
      datasets.
AB  - OBJECTIVES: 1) Describe probabilistic linkage (PL) for road trauma and
      rehabilitation records in New South Wales (NSW) Australia. 2) Determine the
      accuracy of linkage for these records. METHODS: Data were extracted from the NSW
      Trauma Registry for all road trauma admissions for the years 2009-2012 and from
      Australasian Rehabilitation Outcomes Centre for January 2009 to June 2013. PL was
      performed using: age; sex; residential postcode; and date of acute discharge =
      date of admission to rehabilitation. False matches were cases that linked but
      were not true matches; they were determined by manual review. Reasons for
      incomplete linkages were explored. The benefits and limitations of the linked
      study dataset are described. RESULTS: Of 3,256 road trauma records, 683 were
      matched to rehabilitation records. Using the field of 'discharge destination'
      from the trauma records, 265 patients with unmatched records were discharged to
      inpatient rehabilitation (missed matches). This gave an overall 72% linkage rate
      (or sensitivity) using PL. There were 16 cases of false matches, giving a
      specificity of 99%. CONCLUSION: It was feasible to use PL to link road trauma and
      rehabilitation datasets in the absence of identifiers. However, this needed to be
      combined with careful manual review before the linked dataset could be used to
      make inferences on trauma rehabilitation outcomes. IMPLICATION: PL may be a cost
      effective way to capture inpatient rehabilitation outcomes of multi-trauma
      patients.

PMID- 27028099
TI  - Early introduction of palliative care and advanced care planning for children
      with complex chronic medical conditions: a pilot study.
AB  - BACKGROUND: Children with complex chronic medical conditions benefit from early
      introduction of palliative care services and advanced care planning for symptom
      management and to support quality of life and medical decision-making. This study
      evaluated whether introducing palliative care during primary care appointments
      (1) was feasible; (2) increased access and improved knowledge of palliative care;
      and (3) facilitated advanced care planning. METHODS: Pilot study of a multi-modal
      intervention including targeted education for primary care providers (PCPs), an
      informational packet for families and presence of a palliative care team member
      in the outpatient clinic. PCPs completed pre- and post-surveys assessing
      experience, knowledge and comfort with palliative care. Enrolled families
      received an information packet; a subset also met a palliative care team member.
      All families were encouraged to make an appointment with the palliative care
      team, during which the team assessed palliative care needs and goals of care.
      Upon study completion, the investigators assessed family and PCP satisfaction and
      collected feedback on project feasibility. RESULTS: Twenty families were enrolled
      and received the information packet; 15 met a palliative care team member. Of the
      17 participating families who were reached and completed a post-study survey, 11
      families had never heard of palliative care and 13 were unaware that the
      palliative care team existed. Most families perceived palliative care information
      as 'very helpful' and 'very important'. All would recommend palliative care team
      services to others. Nine families followed up with the palliative care team, but
      none was prepared to complete an advanced care plan. PCPs reported lack of
      training in communicating bad news and conducting goals of care discussions.
      However, they felt increasingly comfortable introducing palliative care to
      families and supported program continuation. CONCLUSIONS: Initiating palliative
      care services in the outpatient primary care setting is logistically challenging
      but increases access to palliative care for children with complex chronic medical
      conditions and improves palliative care knowledge and comfort for PCPs.

PMID- 27028100
TI  - Identification of a novel insertion mutation in FGFR3 that causes thanatophoric
      dysplasia type 1.
AB  - Thanatophoric dysplasia is a type of short-limbed neonatal dwarfism that is
      usually lethal in the perinatal period. It is characterized by short limbs, a
      narrow, bell-shaped thorax, macrocephaly with a prominent forehead, and flattened
      vertebral bodies. These malformations result from autosomal dominant mutations in
      the fibroblast growth factor receptor 3 (FGFR3) gene. In this report, we describe
      a novel FGFR3 insertion mutation in a fetus with shortened limbs, curved femurs,
      and a narrow thorax. The diagnosis of thanatophoric dysplasia type 1 was
      suspected clinically, and FGFR3 sequencing showed a c.742_743insTGT variant,
      which predicts p.R248delinsLC. In vivo studies in zebrafish demonstrated that
      this mutation resulted in the overexpression of zebrafish Fgfr3, leading to the
      over-activation of downstream signaling and dorsalized embryos. To date, no
      insertions or deletions in FGFR3 have been reported to cause thanatophoric
      dysplasia types 1 or 2; therefore, this represents the first report to describe
      such a mutation. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028101
TI  - Internal concentration as a better predictor of metal toxicity than the
      fractional coverage of metals on biotic ligand: Comparison of 3 modeling
      approaches.
AB  - Modeling toxicity of metal mixtures poses unique challenges to the incorporation
      of bioavailability and metal speciation in metal exposures. Three models (models
      I, II, and III) were compared in the present study to predict and interpret the
      toxicity exerted by binary metal mixtures to zebrafish larvae, with the
      assumption of competition between metals based on the biotic ligand model and
      toxic potencies of individual metals. In addition, 3 models were developed by
      substituting binding constants (fMBL ) for internal metal concentrations (CM,int
      ) to directly delineate single-metal and mixture effects on mortality of
      zebrafish larvae. The results indicated that the 3 developed models appeared to
      be much better (p < 0.01) than 3 previous models at assessing the toxicity of
      different metal mixtures and showed 10% to 20% predictive improvement for each
      metal combination, with the toxic equivalency factor-based model II showing the
      best performance at quantifying metal mixture toxicity. The 3 developed models
      generally provided a reasonable framework and descriptions of bioavailability and
      additive (or nearly additive) toxicity for a number of binary metal mixtures.
      Environ Toxicol Chem 2016;35:2721-2733. (c) 2016 SETAC.

PMID- 27028102
TI  - Evaluation of and recommendation for the nomenclature of the CPB2 gene product
      (also known as TAFI and proCPU): communication from the SSC of the ISTH.

PMID- 27028104
TI  - Cadmium-Aluminum Layered Double Hydroxide Microspheres for Photocatalytic CO2
      Reduction.
AB  - We report the synthesis of cadmium-aluminum layered double hydroxide (CdAl LDH)
      using the reaction-diffusion framework. As the hydroxide anions diffuse into an
      agar gel matrix containing the mixture of aluminum and cadmium salts at a given
      ratio, they react to give the LDH. The LDH self-assembles inside the pores of the
      gel matrix into a unique spherical-porous shaped microstructure. The internal and
      external morphologies of the particles are studied by electron microscopy and
      tomography revealing interconnected channels and a high surface area. This
      material is shown to exhibit a promising performance in the photoreduction of
      carbon dioxide using solar light. Moreover, the palladium-decorated version shows
      a significant improvement in its reduction potential at room temperature.

PMID- 27028103
TI  - Modulation of Matrix Metalloproteinases Activity in the Ventral Horn of the
      Spinal Cord Re-stores Neuroglial Synaptic Homeostasis and Neurotrophic Support
      following Peripheral Nerve Injury.
AB  - Modulation of extracellular matrix (ECM) remodeling after peripheral nerve injury
      (PNI) could represent a valid therapeutic strategy to prevent maladaptive
      synaptic plasticity in central nervous system (CNS). Inhibition of matrix
      metalloproteinases (MMPs) and maintaining a neurotrophic support could represent
      two approaches to prevent or reduce the maladaptive plastic changes in the
      ventral horn of spinal cord following PNI. The purpose of our study was to
      analyze changes in the ventral horn produced by gliopathy determined by the
      suffering of motor neurons following spared nerve injury (SNI) of the sciatic
      nerve and how the intrathecal (i.t.) administration of GM6001 (a MMPs inhibitor)
      or the NGF mimetic peptide BB14 modulate these events. Immunohistochemical
      analysis of spinal cord sections revealed that motor neuron disease following SNI
      was associated with increased microglial (Iba1) and astrocytic (GFAP) response in
      the ventral horn of the spinal cord, indicative of reactive gliosis. These
      changes were paralleled by decreased glial aminoacid transporters (glutamate GLT1
      and glycine GlyT1), increased levels of the neuronal glutamate transporter EAAC1,
      and a net increase of the Glutamate/GABA ratio, as measured by HPLC analysis.
      These molecular changes correlated to a significant reduction of mature NGF
      levels in the ventral horn. Continuous i.t. infusion of both GM6001 and BB14
      reduced reactive astrogliosis, recovered the expression of neuronal and glial
      transporters, lowering the Glutamate/GABA ratio. Inhibition of MMPs by GM6001
      significantly increased mature NGF levels, but it was absolutely ineffective in
      modifying the reactivity of microglia cells. Therefore, MMPs inhibition, although
      supplies neurotrophic support to ECM components and restores neuro-glial
      transporters expression, differently modulates astrocytic and microglial response
      after PNI. 

PMID- 27028105
TI  - The impact of caring for an adult with intellectual disability and psychiatric
      comorbidity on carer stress and psychological distress.
AB  - BACKGROUND: Given that carers of individuals with intellectual disability (ID)
      and carers of individuals with psychiatric disorders experience elevated levels
      of stress and psychological distress, carers of individuals with both ID and a
      comorbid psychiatric disorder are potentially at even greater risk for
      psychological difficulties. The aim of the present study was to investigate the
      psychological well-being of carers of adults with a dual diagnosis compared with
      carers of adults with intellectual disability alone. METHOD: Four-hundred and
      forty-two questionnaires were sent to four community services and seventy-five
      family carers of adults with intellectual disability responded. Psychological
      well-being of carers was assessed using the Questionnaire on Resources and Stress
      - Friedrich edition (QRS-F) and the General Health Questionnaire (GHQ). Comorbid
      psychopathology for their family member with ID was assessed using the Reiss
      Screen for Maladaptive Behaviour (RSMB). RESULTS: Twenty-four percent of the
      individuals with ID were reported to have comorbid psychopathology. Between-group
      analyses compared carers of people with ID and comorbid psychopathology to carers
      of people with ID alone. Regression analyses examined the relationship between
      psychopathology and other care-related variables to carer stress and
      psychological distress. Carers of people with ID and comorbid psychopathology
      were found to have significantly higher levels of stress and psychological
      distress than carers of people with ID alone. Autism was found to be the only
      significant predictor of both stress and psychological distress among measures of
      psychopathology. CONCLUSIONS: Additional comorbid psychopathology in individuals
      with intellectual disability has a significant impact on their carers'
      psychological well-being.

PMID- 27028106
TI  - The Influence of Personality Traits on Emotion Expression in Bulimic Spectrum
      Disorders: A Pilot Study.
AB  - Facial expressions are critical in forming social bonds and in signalling one's
      emotional state to others. In eating disorder patients, impairments in facial
      emotion recognition have been associated with eating psychopathology severity.
      Little research however has been carried out on how bulimic spectrum disorder
      (BSD) patients spontaneously express emotions. Our aim was to investigate emotion
      expression in BSD patients and to explore the influence of personality traits.
      Our study comprised 28 BSD women and 15 healthy controls. Facial expressions were
      recorded while participants played a serious video game. Expressions of anger and
      joy were used as outcome measures. Overall, BSD participants displayed less
      facial expressiveness than controls. Among BSD women, expressions of joy were
      positively associated with reward dependence, novelty seeking and self
      directedness, whereas expressions of anger were associated with lower self
      directedness. Our findings suggest that specific personality traits are
      associated with altered emotion facial expression in patients with BSD. Copyright
      (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 27028107
TI  - Pharmacokinetic considerations of antibody therapeutics.

PMID- 27028108
TI  - Noninvasive pH monitoring for bacterial detection in platelet concentrates.
AB  - BACKGROUND: Bacterial contamination of platelet concentrates (PCs) remains the
      prevalent posttransfusion infectious risk. The pH SAFE system, a noninvasive
      method used to measure pH of PC for quality control, was evaluated herein as a
      rapid method to detect bacterial contamination in PCs. STUDY DESIGN AND METHODS:
      Pairs of ABO-D-matched apheresis and buffy coat PCs were pooled and split into
      two pH SAFE platelet bags. One of the bags served as the control unit, while the
      other was inoculated with one of nine clinically relevant bacteria (target
      concentration approx. 1 colony-forming units [CFUs]/mL). The pH of both PCs was
      measured over 7 days of storage at approximately 4-hour intervals during daytime.
      One-milliliter samples were taken at the testing points to determine bacterial
      concentration. RESULTS: PCs with pH values of less than 6.6 or with a pH change
      over time (DeltapH/Deltatime) greater or equal than 0.046 pH units/hr are
      suspected of being contaminated. pH decreased significantly during storage in all
      bacterially inoculated PC at concentrations of more than 10(7) CFUs/mL (p <
      0.0001). A significant decrease in pH (p < 0.0001) was noticed as early as 28
      hours in units with Bacillus cereus and as late as 125 hours in units containing
      Staphylococcus epidermidis. Interestingly, PCs containing Gram-negative species
      showed a decline in pH followed by a rebound. CONCLUSIONS: The pH SAFE system
      allows for repeated, noninvasive pH screening during PC storage. A significant
      decrease in pH could serve as an indicator of clinically significant levels of
      bacterial contamination. Since differences in pH decline were observed among
      bacterial species, continuous pH monitoring in PCs is recommended.

PMID- 27028109
TI  - Cricothyroidotomy - The emergency surgical airway.

PMID- 27028110
TI  - A proportional assist ventilator to unload respiratory muscles experimentally
      during exercise in humans.
AB  - What is the central question of this study? Can a modern proportional assist
      ventilator (PAV) function sufficiently well to unload the respiratory muscles
      during exercise? What is the main finding and its importance? A PAV can be
      constructed with contemporary hardware and software and be used at all exercise
      intensities to unload the respiratory muscles by up to 70%. Previously, PAVs have
      allowed researchers to address many fundamental physiological problems in
      clinical and healthy populations, but those versions are no longer functional or
      available. We describe the creation of a PAV that permits researchers to use it
      as an experimental tool. Manipulation of the normally occurring work of breathing
      (WOB) during exercise can provide insights into whole-body regulatory mechanisms
      in clinical patients and healthy subjects. One method to reduce the WOB uses a
      proportional assist ventilator (PAV). Suitable commercially available units are
      not capable of being used during heavy exercise. This investigation was
      undertaken in order to create a PAV and assess the degree to which the WOB could
      be reduced during exercise. A PAV works by creating a positive mouth pressure (Pm
      ) during inspiration, which consequently reduces the WOB. Spontaneous breathing
      patterns can be maintained, and the amplitude of Pm is calculated using the
      equation of motion and predetermined proportionality constants. We generated
      positive Pm using a breathing apparatus consisting of rigid tubing, solenoid
      valves to control the airflow direction and a proportional valve connected to
      compressed gas. Healthy male and female subjects were able to use the PAV
      successfully while performing cycling exercise over a range of intensities (50
      100% of maximal workload) for different durations (from 30 s to 20 min) and
      different protocols (constant versus progressive workload). Inspiratory WOB was
      reduced up to 90%, while total WOB was reduced by 70%. The greatest reduction in
      WOB (50-75%) occurred during submaximal exercise, but at maximal ventilations
      (>180 l min(-1) ) a 50% reduction was still possible. The calculated change in
      WOB and subsequent reduction in respiratory muscle oxygen consumption resulted in
      equivalent reductions in whole-body oxygen consumption. With adequate
      familiarization and practice, our PAV can consistently reduce the WOB across a
      range of exercise intensities.

PMID- 27028111
TI  - Plasma fatty acid patterns reflect dietary habits and metabolic health: A cross
      sectional study.
AB  - SCOPE: Using pattern analysis, we investigated the relationship between plasma
      fatty acid patterns, dietary intake, and biomarkers of metabolic health using
      data from the Irish National Adult Nutrition Survey. METHODS AND RESULTS: Plasma
      fatty acid patterns were derived from 26 plasma fatty acids using k-means cluster
      analysis. Four clusters were identified, each with a distinct fatty acid profile.
      Cluster 1 included high proportions of linoleic acid (LA) and low proportions of
      stearic acid (SA); cluster 2 was higher in n-3 polyunsaturated fatty acids and
      SA; the profile of cluster 3 was higher in very-long-chain saturated fatty acid
      (VLCSFA) and lower in alpha-linolenic acid (ALA) (cluster 3); while cluster 4 was
      higher in fatty acids related to de novo lipogenesis and 20:3n-6 and lower in LA
      (cluster 4). In general, cluster 4 was associated with adverse metabolic profile
      and higher metabolic risk (p < 0.033). Clusters 2 and 3 were associated with
      healthier and protective phenotypes (p < 0.033). CONCLUSION: Distinct fatty acid
      patterns were identified which were related to demographics, dietary habits, and
      metabolic profile. A pattern higher in VLCSFA and lower in ALA was associated
      with healthier metabolic outcome.

PMID- 27028112
TI  - Simultaneous whole body (18)F-fluorodeoxyglucose positron emission tomography
      magnetic resonance imaging for evaluation of pediatric cancer: Preliminary
      experience and comparison with (18)F-fluorodeoxyglucose positron emission
      tomography computed tomography.
AB  - AIM: To describe our preliminary experience with simultaneous whole body (18)F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography and magnetic
      resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients.
      METHODS: This prospective, observational, single-center study was Health
      Insurance Portability and Accountability Act-compliant, and institutional review
      board approved. To be eligible, a patient was required to: (1) have a known or
      suspected cancer diagnosis; (2) be under the care of a pediatric
      hematologist/oncologist; and (3) be scheduled for clinically indicated (18)F-FDG
      positron emission tomography-computed tomography (PET-CT) examination at our
      institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET
      CT examinations were performed using standard department protocols. PET-MRI
      studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body
      T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No
      additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET
      MRI examinations were reviewed by consensus by two study personnel. Test
      performance characteristics of PET-MRI, for the detection of malignant lesions,
      including FDG maximum standardized uptake value (SUVmax) and minimum apparent
      diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET
      CT as a reference standard. RESULTS: A total of 10 whole body PET-MRI exams were
      performed in 7 pediatric oncology patients. The mean patient age was 16.1 years
      (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and
      21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent
      correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93).
      PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant
      lesions using PET-CT reference. Whole body DWI was also evaluated: the mean
      ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than that of
      benign lesions (1246.2 + 417.3; P = 0.0003; Student's t test). A range of ADCmin
      thresholds for malignancy were evaluated, from 0.5-1.5 * 10(-3) mm(2)/s. The 1.0
      * 10(-3) ADCmin threshold performed best compared with PET-CT reference (68.3%
      accuracy). However, the accuracy of PET-MRI SUVmax was significantly better than
      ADCmin for detecting malignant lesions compared with PET-CT reference (P <
      0.0001; two-tailed McNemar's test). CONCLUSION: These results suggest a clinical
      role for simultaneous whole body PET-MRI in evaluating pediatric cancer patients.

PMID- 27028113
TI  - From Clinging to Digging: The Postembryonic Skeletal Ontogeny of the Indian
      Purple Frog, Nasikabatrachus sahyadrensis (Anura: Nasikabatrachidae).
AB  - The Indian Purple frog, Nasikabatrachus sahyadrensis, occupies a basal
      phylogenetic position among neobatrachian anurans and has a very unusual life
      history. Tadpoles have a large ventral oral sucker, which they use to cling to
      rocks in torrents, whereas metamorphs possess adaptations for life underground.
      The developmental changes that underlie these shifts in habits and habitats, and
      especially the internal remodeling of the cranial and postcranial skeleton, are
      unknown. Using a nearly complete metamorphic series from free-living larva to
      metamorph, we describe the postembryonic skeletal ontogeny of this ancient and
      unique monotypic lineage. The torrent-dwelling larva possesses a dorsoventrally
      flattened body and a head with tiny dorsal eyes, robust lower and upper jaw
      cartilages, well-developed trabecular horns, and a definable gap between the
      trabecular horns and the tip of the snout. Unlike tadpoles of many other frogs,
      those of Nasikabatrachus retain larval mouthparts into late metamorphic stages.
      This unusual feature enables the larvae to maintain their clinging habit until
      near the end of metamorphosis. The subsequent ontogenetic shift from clinging to
      digging is correlated with rapid morphological changes and behavioral
      modifications. Metamorphs are equipped with a shortened tibiafibula and ossified
      prehallical elements, which likely facilitate initial digging using the hind
      limbs. Subsequently, the frogs may shift to headfirst burrowing by using the
      wedge-shaped skull, anteriorly positioned pectoral girdle, well-developed humeral
      crests and spatula-shaped forelimbs. The transition from an aquatic life in
      torrents to a terrestrial life underground entails dramatic changes in skeletal
      morphology and function that represent an extreme in metamorphic remodeling. Our
      analysis enhances the scope for detailed comparative studies across anurans, a
      group renowned for the diversity of its life history strategies. 

PMID- 27028114
TI  - The terms 'autacoid', 'hormone' and 'chalone' and how they have shifted with
      time.
AB  - The increase of knowledge in a particular field (endocrinology) can be understood
      if one follows how certain key concepts were constructed and transformed over
      time. To explore such construction and transformation (shifts in meaning), we
      studied the use of the concepts 'autacoid' and 'chalone' in a period of one
      century (1916-2016), since the introduction of these concepts by the British
      professor of physiology Sir Sharpey-Schafer. We could identify that the use of
      'autacoid' shifted from a very broad category encompassing both stimulating and
      inhibiting hormones, in the period 1916-1960, to a much more specific use of the
      term for locally produced bioactive molecules, from the 1960s onwards. Histamine
      was the first compound seen as an 'autacoid', followed by prostaglandins, ATP,
      ADP and bradykinin, and from 1993 onwards, compounds such as
      'palmitoylethanolamide' were also classified as 'autacoids'. For 'chalone', a
      comparable shift was noticed around the 1960s, when the concept suddenly changed
      from the category of inhibiting hormones into a substance that is produced within
      a tissue, inhibiting mitosis of the cells of that tissue. For both concept
      shifts, we could not find any argument. Around 1980, authors started to relate
      autacoids to various promising indications in the field of inflammation and
      immune modulation. The Nobel laureate Rita Levi-Montalcini gave an extra
      dimension to the concept autacoid in 1993, and introduced a new class of
      compounds modulating mast cells, the ALIAmides (from Autacoid Local Inflammation
      Antagonist), of which palmitoylethanolamide was the prototype. Our exploration
      demonstrates that biomedical concepts can be constructed and defined differently
      as time goes by, while concept transformations seem to emerge without arguments. 

PMID- 27028115
TI  - A rare complication after allogeneic stem cell transplantation: post-transplant
      erythrocytosis.
AB  - Post-transplant erythrocytosis is an infrequent complication and has been
      reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in
      aplastic anemia, acute myeloid leukemia, and chronic myeloid leukemia. The pre
      disposing factors and treatment are not clearly defined. We present 11 post
      transplant erythrocytosis cases. More studies should be conducted to distinguish
      the pathogenesis and follow-up for this rare complication. 

PMID- 27028117
TI  - Medical Education - Evolving.

PMID- 27028116
TI  - Seeing the Forest through the Trees: Considering Roost-Site Selection at Multiple
      Spatial Scales.
AB  - Conservation of bat species is one of the most daunting wildlife conservation
      challenges in North America, requiring detailed knowledge about their ecology to
      guide conservation efforts. Outside of the hibernating season, bats in temperate
      forest environments spend their diurnal time in day-roosts. In addition to simple
      shelter, summer roost availability is as critical as maternity sites and
      maintaining social group contact. To date, a major focus of bat conservation has
      concentrated on conserving individual roost sites, with comparatively less focus
      on the role that broader habitat conditions contribute towards roost-site
      selection. We evaluated roost-site selection by a northern population of
      federally-endangered Indiana bats (Myotis sodalis) at Fort Drum Military
      Installation in New York, USA at three different spatial scales: landscape,
      forest stand, and individual tree level. During 2007-2011, we radiotracked 33
      Indiana bats (10 males, 23 females) and located 348 roosting events in 116 unique
      roost trees. At the landscape scale, bat roost-site selection was positively
      associated with northern mixed forest, increased slope, and greater distance from
      human development. At the stand scale, we observed subtle differences in roost
      site selection based on sex and season, but roost selection was generally
      positively associated with larger stands with a higher basal area, larger tree
      diameter, and a greater sugar maple (Acer saccharum) component. We observed no
      distinct trends of roosts being near high-quality foraging areas of water and
      forest edges. At the tree scale, roosts were typically in American elm (Ulmus
      americana) or sugar maple of large diameter (>30 cm) of moderate decay with loose
      bark. Collectively, our results highlight the importance of considering day roost
      needs simultaneously across multiple spatial scales. Size and decay class of
      individual roosts are key ecological attributes for the Indiana bat, however,
      larger-scale stand structural components that are products of past and current
      land use interacting with environmental aspects such as landform also are
      important factors influencing roost-tree selection patterns. 

PMID- 27028118
TI  - Ocean Acidification and Increased Temperature Have Both Positive and Negative
      Effects on Early Ontogenetic Traits of a Rocky Shore Keystone Predator Species.
AB  - The combined effect of ocean acidification and warming is expected to have
      significant effects on several traits of marine organisms. The gastropod
      Concholepas concholepas is a rocky shore keystone predator characteristic of the
      south-eastern Pacific coast of South America and an important natural resource
      exploited by small-scale artisanal fishermen along the coast of Chile and Peru.
      In this study, we used small juveniles of C. concholepas collected from the rocky
      intertidal habitats of southern Chile (39  degrees S) to evaluate under
      laboratory conditions the potential consequences of projected near-future levels
      of ocean acidification and warming for important early ontogenetic traits. The
      individuals were exposed long-term (5.8 months) to contrasting pCO2 (ca. 500 and
      1400 MUatm) and temperature (15 and 19  degrees C) levels. After this period we
      compared body growth traits, dislodgement resistance, predator-escape response,
      self-righting and metabolic rates. With respect to these traits there was no
      evidence of a synergistic interaction between pCO2 and temperature. Shell growth
      was negatively affected by high pCO2 levels only at 15  degrees C. High pCO2
      levels also had a negative effect on the predator-escape response. Conversely,
      dislodgement resistance and self-righting were positively affected by high pCO2
      levels at both temperatures. High tenacity and fast self-righting would reduce
      predation risk in nature and might compensate for the negative effects of high
      pCO2 levels on other important defensive traits such as shell size and escape
      behaviour. We conclude that climate change might produce in C. concholepas
      positive and negative effects in physiology and behaviour. In fact, some of the
      behavioural responses might be a consequence of physiological effects, such as
      changes in chemosensory capacity (e.g. predator-escape response) or secretion of
      adhesive mucous (e.g. dislodgement resistance). Moreover, we conclude that
      positive behavioural responses may assist in the adaptation to negative
      physiological impacts, and that this may also be the case for other benthic
      organisms.

PMID- 27028119
TI  - TRPML1 as lysosomal fusion guard.

PMID- 27028120
TI  - Comparison of 30-day mortality and myocardial scar indices for patients treated
      with prehospital reduced dose fibrinolytic followed by percutaneous coronary
      intervention versus percutaneous coronary intervention alone for treatment of ST
      elevation myocardial infarction.
AB  - OBJECTIVES: We investigated whether prehospital, reduced dose fibrinolysis
      coupled with urgent percutaneous coronary intervention (FAST-PCI) reduces
      mortality and cardiac magnetic resonance (CMR) measures of infarct size, compared
      with primary percutaneous coronary intervention (PPCI), in patients with ST
      elevation myocardial infarction (STEMI). BACKGROUND: Current standard therapy for
      STEMI is PPCI. However, FAST-PCI may shorten ischemic time (IT) and improve
      outcomes. METHODS: Eligible STEMI patients received prehospital, reduced dose
      fibrinolysis along with standard therapy, and were transported for urgent
      percutaneous coronary intervention, or else they received usual treatment without
      prehospital fibrinolysis. Patients were divided retrospectively into four groups
      based on IT (<120, 120-179, 180-239 min, >=240) for a mortality analysis cohort,
      and into three groups (<120, 120-179, >=180 min) for a CMR analysis cohort.
      Within each IT group, patients were compared by FAST-PCI vs. PPCI strategy.
      RESULTS: Between 1/2007 and 2/2014, 1,112 STEMI patients were treated. FAST-PCI
      was employed in 551 and PPCI in 561. Of these, 357 (32.1%) underwent CMR. The
      treatment groups were well matched. In STEMI patients with short IT (<120 and 120
      179 min groups), those treated by FAST-PCI had lower 30-day mortality and
      myocardial scar sizes compared with PPCI treatment. For IT >=180 min, the
      mortalities and myocardial scar sizes were equivalent for both groups.
      CONCLUSIONS: In STEMI patients with IT <180 min, FAST-PCI may reduce 30-day
      mortality and myocardial scar size compared with PPCI. This suggests that infarct
      interventions must be instituted within 3 hr of symptom onset in order to detect
      an optimal beneficial effect both clinically and by CMR measurement. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27028121
TI  - Subclinical hyperthyroidism: first do no harm.

PMID- 27028122
TI  - Multipurpose Black-Phosphorus/hBN Heterostructures.
AB  - Black phosphorus (BP) has recently emerged as a promising semiconducting two
      dimensional material. However, its viability is threatened by its instability in
      ambient conditions and by the significant decrease of its band gap in
      multilayers. We show that one could solve all the aforementioned problems by
      interfacing BP with hexagonal boron nitride (hBN). To this end, we simulate
      large, rotated hBN/BP interfaces using linear-scaling density functional theory.
      We predict that hBN-encapsulation preserves the main electronic properties of the
      BP monolayer, while hBN spacers can be used to counteract the band gap reduction
      in stacked BP. Finally, we propose a model for a tunneling field effect
      transistor (TFET) based on hBN-spaced BP bilayers. Such BP TFETs would sustain
      both low-power and fast-switching operations, including negative differential
      resistance behavior with peak-to-valley ratios of the same order of magnitude as
      those encountered in transition metal dichalcogenide TFETs. 

PMID- 27028123
TI  - Re-exploration of the Codon Context Effect on Amber Codon-Guided Incorporation of
      Noncanonical Amino Acids in Escherichia coli by the Blue-White Screening Assay.
AB  - The effect of codon context on amber codon-guided incorporation of noncanonical
      amino acids (NAAs) has been previously examined by antibiotic selection. Here, we
      re-explored this effect by screening a library in which three nucleotides
      upstream and downstream of the amber codon were randomised, and inserted within
      the lacZ-alpha gene. Thousands of clones were obtained and distinguished by the
      depth of blue colour upon exposure to X-gal. Large-scale sequencing revealed
      remarkable preferences in nucleotides downstream of the amber codon, and moderate
      preferences for upstream nucleotides. Nucleotide preference was quantified by a
      dual-luciferase assay, which verified that the optimum context for NAA
      incorporation, AATTAGACT, was applicable to different proteins. Our work provides
      a general guide for engineering amber codons into genes of interest in bacteria.

PMID- 27028124
TI  - Persistent supravenous erythematous eruption-like changes from antibiotics.

PMID- 27028127
TI  - Optimal slopes and speeds in uphill ski mountaineering: a laboratory study.
AB  - PURPOSE: The purpose of this study was to estimate the energy cost of linear (EC)
      and vertical displacement (ECvert), mechanical efficiency and main stride
      parameters during simulated ski mountaineering at different speeds and gradients,
      to identify an optimal speed and gradient that maximizes performance. METHODS: 12
      subjects roller skied on a treadmill at three different inclines (10, 17 and 24
      %) at three different speeds (approximately 70, 80 and 85 % of estimated peak
      heart rate). Energy expenditure was calculated by indirect calorimetry, while
      biomechanical parameters were measured with an inertial sensor-based system.
      RESULTS: At 10 % there was no significant change with speed in EC, ECvert and
      mechanical efficiency. At 17 and 24 % the fastest speed was significantly more
      economical. There was a significant effect of gradient on EC, ECvert and
      mechanical efficiency. The most economical gradient was the steepest one. There
      was a significant increase of stride frequency with speed. At steep gradients
      only, relative thrust phase duration decreased significantly, while stride length
      increased significantly with speed. There was a significant effect of gradient on
      stride length (decrease with steepness) and relative thrust phase duration
      (increase with steepness). CONCLUSION: A combination of a decreased relative
      thrust phase duration with increased stride length and frequency decreases
      ECvert. To minimize the energy expenditure to reach the top of a mountain and to
      optimize performance, ski-mountaineers should choose a steep gradient (~24 %)
      and, provided they possess sufficient metabolic scope, combine it with a fast
      speed (~6 km h(-1)).

PMID- 27028129
TI  - Body Mass Index Predicts Progression of Mild Cognitive Impairment to Dementia.
AB  - AIMS: To examine the relationship between body mass index (BMI) and progression
      to dementia and Alzheimer's disease (AD) in mild cognitive impairment (MCI).
      MATERIALS AND METHODS: Two hundred and twenty-eight MCI subjects (mean age 74.04
      +/- 6.94 years; 57% female) from a memory clinic were followed for 2.40 +/- 1.58
      years. Baseline height and weight were used to calculate the BMI. The main
      outcome was progression to dementia (DSM-IV criteria) and AD (NINCDS-ADRDA
      criteria). Cox proportional hazard models were used to assess the longitudinal
      association of BMI with dementia and AD, adjusting for a comprehensive set of
      covariates, including vascular risk factors/diseases and neuroimaging profiles.
      RESULTS: Out of 228 subjects with MCI, 117 (51.3%) progressed to dementia. Eighty
      nine (76%) of the incident dementia cases had AD. In both unadjusted and multi
      adjusted models, a higher BMI was associated with a reduced risk of dementia
      (multi-adjusted HR 0.9; 95% CI 0.8-0.9) and AD (multi-adjusted HR 0.9; 95% CI 0.8
      0.9). Being underweight increased the risk of all types of dementia (multi
      adjusted HR 2.5; 95% CI 1.2-5.1) but was not specifically associated with AD
      (multi-adjusted HR 2.2; 95% CI 0.9-5.3). CONCLUSIONS: BMI predicted progression
      of MCI to dementia and AD. In particular, a higher BMI was associated with a
      lower risk of dementia and AD, and underweight was associated with a higher risk
      of dementia. BMI assessment may improve the prognostic accuracy of MCI in
      clinical practice.

PMID- 27028128
TI  - A Randomised Controlled Trial of Consent Procedures for the Use of Residual
      Tissues for Medical Research: Preferences of and Implications for Patients,
      Research and Clinical Practice.
AB  - BACKGROUND: Despite much debate, there is little evidence on consequences of
      consent procedures for residual tissue use. Here, we investigated these
      consequences for the availability of residual tissue for medical research,
      clinical practice, and patient informedness. METHODS: We conducted a randomised
      clinical trial with three arms in six hospitals. Participants, patients from whom
      tissue had been removed for diagnosis or treatment, were randomised to one of
      three arms: informed consent, an opt-out procedure with active information
      provision (opt-out plus), and an opt-out procedure without active information
      provision. Participants received a questionnaire six weeks post-intervention; a
      subsample of respondents was interviewed. Health care providers completed a pre-
      and post-intervention questionnaire. We assessed percentage of residual tissue
      samples available for medical research, and patient and health care provider
      satisfaction and preference. Health care providers and outcome assessors could
      not be blinded. RESULTS: We randomised 1,319 patients, 440 in the informed
      consent, 434 in the opt-out plus, and 445 in the opt-out arm; respectively 60.7%,
      100%, and 99.8% of patients' tissue samples could be used for medical research.
      Of the questionnaire respondents (N = 224, 207, and 214 in the informed consent,
      opt-out plus, and opt-out arms), 71%, 69%, and 31%, respectively, indicated being
      (very) well informed. By questionnaire, the majority (53%) indicated a preference
      for informed consent, whereas by interview, most indicated a preference for opt
      out plus (37%). Health care providers (N = 35) were more likely to be (very)
      satisfied with opt-out plus than with informed consent (p = 0.002) or opt-out (p
      = 0.039); the majority (66%) preferred opt-out plus. CONCLUSION: We conclude that
      opt-out with information (opt-out plus) is the best choice to balance the
      consequences for medical research, patients, and clinical practice, and is
      therefore the most optimal consent procedure for residual tissue use in Dutch
      hospitals. TRIAL REGISTRATION: Dutch Trial Register NTR2982.

PMID- 27028130
TI  - Gastrointestinal Microbiota and Their Contribution to Healthy Aging.
AB  - Studies on populations at different ages have shown that after birth, the
      gastrointestinal (GI) microbiota composition keeps evolving, and this seems to
      occur especially in old age. Significant changes in GI microbiota composition in
      older subjects have been reported in relation to diet, drug use and the settings
      where the older subjects are living, that is, in community nursing homes or in a
      hospital. Moreover, changes in microbiota composition in the old age have been
      related to immunosenescence and inflammatory processes that are
      pathophysiological mechanisms involved in the pathways of frailty. Frailty is an
      age-related condition of increased vulnerability to stresses due to the
      impairment in multiple inter-related physiologic systems that are associated with
      an increased risk of adverse outcomes, such as falls, delirium,
      institutionalization, hospitalization and death. Preliminary data suggest that
      changes in microbiota composition may contribute to the variations in the
      biological, clinical, functional and psycho-social domains that occur in the
      frail older subjects. Multidimensional evaluation tools based on a Comprehensive
      Geriatric Assessment (CGA) have demonstrated to be useful in identifying and
      measuring the severity of frailty in older subjects. Thus, a CGA approach should
      be used more widely in clinical practice to evaluate the multidimensional effects
      potentially related to GI microbiota composition of the older subjects.
      Probiotics have been shown to be effective in restoring the microbiota changes of
      older subjects, promoting different aspects of health in elderly people as
      improving immune function and reducing inflammation. Whether modulation of GI
      microbiota composition, with multi-targeted interventions, could have an effect
      on the prevention of frailty remains to be further investigated in the
      perspective of improving the health status of frail 'high risk' older
      individuals. 

PMID- 27028132
TI  - Isolation and Cultivation of Anaerobes.
AB  - Anaerobic microorganisms play important roles in different biotechnological
      processes. Their complex metabolism and special cultivation requirements have led
      to less isolated representatives in comparison to their aerobic counterparts. In
      view of that, the isolation and cultivation of anaerobic microorganisms is still
      a promising venture, and conventional methodologies as well as considerations and
      modifications are presented here. An insight into new methodologies and devices
      as well as a discussion on future perspectives for the cultivation of anaerobes
      may open the prospects of the exploitation of these microorganisms as a source
      for biotechnology.

PMID- 27028131
TI  - Glycaemic control modifies the haptoglobin 2 allele-conferred susceptibility to
      coronary artery disease in Type 1 diabetes.
AB  - AIMS: We aimed to assess whether the association of the haptoglobin 2 allele with
      coronary artery disease is modified by glycaemic control in a prospective cohort
      study of individuals with childhood-onset Type 1 diabetes. METHODS: Coronary
      artery disease events (death from coronary artery disease, confirmed myocardial
      infarction, stenosis >=50%, revascularization) were assessed between 1986 and
      2013 among 480 individuals with Type 1 diabetes (baseline age 28 years; diabetes
      duration 19 years). Better glycaemic control was defined as an updated mean HbA1c
      during follow-up of <8% (64 mmol/mol). RESULTS: In crude models, the incidence of
      coronary artery disease increased with the number of haptoglobin 2 alleles
      (hazard ratio 1.34, 95% CI 1.05-1.71). This association was more pronounced in
      those with better than in those with worse glycaemic control (P interaction =
      0.05) and remained essentially unaltered after multivariable adjustments (hazard
      ratio 2.65, 95% CI 1.30-5.41 in those with better glycaemic control and hazard
      ratio 1.20, 95% CI 0.93-1.56 in those with worse glycaemic control). CONCLUSIONS:
      These results suggest that, although better control may reduce the incidence of
      coronary artery disease in Type 1 diabetes, a residual risk related to the
      haptoglobin 2 allele remains.

PMID- 27028133
TI  - Randomized, Controlled Trial of Acupuncture for Fatigue in Parkinson's Disease.
AB  - BACKGROUND: Fatigue is a common and debilitating nonmotor symptom of PD. Because
      preliminary evidence suggests that acupuncture improves fatigue in other
      conditions, we sought to test its efficacy in PD. METHODS: Ninety-four PD
      patients with moderate-to-high fatigue were randomized to receive 6 weeks of
      biweekly real or sham acupuncture. The primary outcome was change on the Modified
      Fatigue Impact Scale at 6 weeks. Secondary outcomes included sleep, mood, quality
      of life, and maintenance of benefits at 12 weeks. RESULTS: Both groups showed
      significant improvements in fatigue at 6 and 12 weeks, but with no significant
      between-group differences. Improvements from baseline in mood, sleep, and quality
      of life were noted without between-group differences. Overall, 63% of patients
      reported noticeable improvements in their fatigue. No serious adverse events were
      observed. CONCLUSIONS: Acupuncture may improve PD-related fatigue, but real
      acupuncture offers no greater benefit than sham treatments. PD-related fatigue
      should be added to the growing list of conditions that acupuncture helps
      primarily through nonspecific or placebo effects. (c) 2016 International
      Parkinson and Movement Disorder Society.

PMID- 27028134
TI  - Health technology assessment in Australia: a role for clinical registries?
AB  - Objective Health technology assessment (HTA) is a process of assessing evidence
      to inform policy decisions about public subsidy of new drugs and medical
      procedures. Where evidence is uncertain but the technology itself is promising,
      funders may recommend funding on an interim basis. It is unknown whether evidence
      from clinical registries is used to resolve uncertainties identified in interim
      funded decisions made by Australian HTA bodies. Therefore, the present study
      evaluated the role of evidence from clinical registries in resolving evidence
      uncertainties identified by the Medical Services Advisory Committee (MSAC).
      Methods All HTAs considered by MSAC between 1998 and 2015 were reviewed and
      assessments that recommended interim funding were identified. The MSAC website
      was searched to identify reassessments of these recommendations and sources of
      evidence used to resolve the uncertainties were identified. Results Of 173 HTA
      reports considered by MSAC, 17 (10%) contained an interim funding recommendation.
      Eight recommendations cited uncertainty around safety, 15 cited uncertainty
      around clinical effectiveness and 13 cited uncertainty around economics (cost
      effectiveness and/or budget impact). Of the 17 interim funding recommendations,
      11 (65%) have been reassessed. Only two reassessments relied on clinical registry
      evidence to resolve evidence gaps identified at the time of the interim funding
      recommendation. Conclusions Clinical registries are underused as a source of
      evidence for resolving uncertainties around promising new health technologies in
      Australia. An open dialogue between stakeholders on the role of registries in
      this context is needed. What is known about the topic? HTA is a process of
      assessing the evidence to inform policy decisions about public subsidy of new
      health technologies (e.g. pharmaceuticals, diagnostic tests, medical procedures).
      Where evidence is uncertain but the technology under evaluation is promising,
      funders may recommend the funding of the technology on a temporary basis while
      additional evidence is collected. Clinical registries have been suggested as a
      means of collecting additional evidence in these situations. What is does this
      paper add? It is currently unknown whether evidence from clinical registries is
      used to resolve uncertainties identified at the time that temporary (interim)
      funding decisions are made by Australia's HTA bodies, in particular MSAC. The
      present study found that MSAC rarely relies on the interim funding mechanism
      (17/173 assessments). Of the 11 subsequent reassessments of interim
      recommendations, two relied on registry evidence to provide Australian-specific
      data for addressing uncertainties around long-term safety, effectiveness and cost
      effectiveness. These findings suggest that clinical registries, although a
      feasible source of evidence for HTAs, are rarely used for this purpose. What are
      the implications for practitioners? Given the registries' ability to resolve both
      a wider range of questions than those typically addressed by randomised control
      trials and applicability to a wider group of patients (and, hence, providing
      estimates of outcomes that are more generalisable), the potential of clinical
      registries to resolve HTA issues needs more attention from both researchers and
      decision makers. Stakeholder collaboration to define the evidence requirements
      for new technologies early in their development phase would be valuable to
      determine the potential role for clinical registries.

PMID- 27028135
TI  - Federal Government's Proposed Expansion of Regulation of Biospecimen Research
      Should Be Reconsidered.
AB  - In September, the U.S. Department of Health and Human Services, together with
      other federal agencies, announced proposed changes to the rules governing human
      subjects research. This Commentary discusses how the proposals would affect
      research using biospecimens that is essential to the future success of precision
      medicine. We argue that the proposed changes unnecessarily burden such research,
      without meaningfully advancing the interests of donors. They should be revised
      before being finalized.

PMID- 27028136
TI  - Cross-cultural validation of the 20-item Toronto Alexithymia Scale in Chinese
      adolescents.
AB  - WHAT IS KNOWN ON THE SUBJECT?: The TAS-20 is the most widely used self-reported
      questionnaire to assess the level of alexithymia in students and community and
      clinical samples. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The TAS-20-C
      exhibited high levels of reliability and validity, indicating that it is
      appropriate for the assessment of alexithymia in Chinese adolescents. WHAT ARE
      THE IMPLICATIONS FOR PRACTICE?: Screening adolescents who are at risk of
      alexithymia through the TAS-20 could help to perform necessary and effective
      precautions to decrease the adverse effects of alexithymia, such as the risks of
      developing depressive mood and behavioral problems. ABSTRACT: Purpose The aim of
      this study was to examine the psychometric properties of the Chinese version of
      the 20-item Toronto Alexithymia Scale (TAS-20-C) in a sample of Chinese
      adolescents. Method Adolescents (n = 1260) recruited from three schools in
      mainland China completed the TAS-20-C, the somatization subscale of the Symptom
      Checklist 90 (SCL-90) and Center for Epidemiological Studies Depression Scale
      (CES-D). Five different factorial models of the TAS-20 were tested using
      confirmatory factor analysis (CFA). Cronbach's alpha, mean inter-item
      correlations and predictive validity were also evaluated. Results Among those
      five different factorial models, the four-factor structure model was suitable and
      invariant across gender and age in this sample. The TAS-20-C demonstrated
      adequate internal reliability. Gender and age accounted for insignificant amounts
      of variability in total TAS-20-C and factor scores. TAS-20-C total and subscale
      scores were correlated significantly with SCL-90 somatization subscale and CES-D.
      Girls scored higher than boys on difficulty identifying feelings (DIF) and
      pragmatic thinking (PR) subscales. DIF and lack of subjective significance or
      importance of emotions (IMs) subscale scores were higher among younger than among
      middle and older adolescents. Implications for Practice Validating the TAS-20 in
      adolescents is quite important to use it in evaluating adolescents' alexithymia,
      and screen those at risk of alexithymia.

PMID- 27028137
TI  - Laparoscopy or open surgery for the treatment of hydatid cyst?
AB  - The laparoscopic approach has taken a prominent role in the last decades for
      various surgical conditions, including liver hydatid cyst. However there is
      controversy about whether it can replace open surgery. Using Epistemonikos
      database, which is maintained by screening 30 databases, we identified three
      systematic reviews which together include four relevant studies, all
      nonrandomized. We combined the evidence using meta-analysis and generated a
      summary of findings table following the GRADE approach. We concluded it is
      unclear whether laparoscopy for hepatic hydatid cyst reduces mortality, morbidity
      or recurrence compared with open surgery because the certainty of the evidence is
      very low. 

PMID- 27028138
TI  - Rectal mobilization: the place of Denonvilliers' fascia and inconsistencies in
      the literature.
AB  - Confusion remains as to what is meant by Denonvilliers' fascia. This review
      searched the literature on pelvic surgical anatomy to determine whether there is
      agreement with Denonvilliers' original description and its implication in
      defining the correct anterior plane of dissection when mobilizing the rectum. The
      original French description of the fascia was translated into English and then
      compared both with French and with English studies identified by searching
      PubMed, Medline and Scopus from 1836 to June 2015. Special emphasis was given to
      the years between 1980 and 2015 in order to capture the literature pertinent to,
      and following on from, the description of total mesorectal excision for rectal
      cancer. The final literature search revealed 16 studies from the original 2150
      citations. Much of the debate was concerned with the origin and development of
      the fascia, arising from either the 'fusion' or the 'condensation' of local
      primitive tissue into a mature 'multilayered' structure. Controversy regarding
      the correct plane of rectal mobilization occurs as a result of different
      interpretations by surgeons, anatomists and radiologists and bears little
      resemblance to Denonvilliers' original description. This may reflect wide
      anatomical variability in the adult pelvis or a form of dissection artefact.
      Further study is required to investigate this. Logically, for both men and women,
      the plane of rectal mobilization should be behind Denonvilliers' fascia and
      between it and the fascia propria of the rectum.

PMID- 27028139
TI  - Variation in myogenic differentiation 1 mRNA abundance is associated with beef
      tenderness in Nelore cattle.
AB  - The myogenic differentiation 1 gene (MYOD1) has a key role in skeletal muscle
      differentiation and composition through its regulation of the expression of
      several muscle-specific genes. We first used a general linear mixed model
      approach to evaluate the association of MYOD1 expression levels on individual
      beef tenderness phenotypes. MYOD1mRNA levels measured by quantitative polymerase
      chain reactions in 136 Nelore steers were significantly associated (P <= 0.01)
      with Warner-Bratzler shear force, measured on the longissimus dorsi muscle after
      7 and 14 days of beef aging. Transcript abundance for the muscle regulatory gene
      MYOD1 was lower in animals with more tender beef. We also performed a co
      expression network analysis using whole transcriptome sequence data generated
      from 30 samples of longissimus muscle tissue to identify genes that are
      potentially regulated by MYOD1. The effect of MYOD1 gene expression on beef
      tenderness may emerge from its function as an activator of muscle-specific gene
      transcription such as for the serum response factor (C-fos serum response element
      binding transcription factor) gene (SRF), which determines muscle tissue
      development, composition, growth and maturation.

PMID- 27028140
TI  - A 10-yr follow-up study for the detection of peripheral neuropathy in young
      patients with type 1 diabetes.
AB  - OBJECTIVE: The main objective of this work was to follow-up the development of
      diabetic neuropathy (DN) and its severity in patients with type 1 diabetes over
      10 yr. Our intention was also to observe risk factor changes and verify which of
      them influence the development of neuropathy. The other objective was
      longitudinal study of electrophysiological parameters, focusing on the early
      diagnosis of DN. METHODS: The prospective study comprised of 62 young patients
      with type 1 diabetes mellitus (DM) aged 13.9 +/- 5.89 yr, with diabetes duration
      of 5.56 +/- 5.11 yr, treated with an intensified insulin regimen. All patients
      underwent a detailed clinical neurological examination, nerve conduction study
      (NCS) and biothesiometry three times (baseline, after 5 yr, after 10 yr).
      RESULTS: During the follow-up there was an increase in DN prevalence from 24.2%
      to 62.9% (p < 0.001). The proportion of patients with subclinical neuropathy
      increased from 17.7% to 46.8% (p < 0.001) and patients with clinical neuropathy
      from 6.5% to 16.1% (p < 0.001). The main contribution factors for rapid growth of
      the DN prevalence were poor glycaemic control, diabetes duration and patient's
      age. Regarding the conduction parameters, the most significant changes were
      observed in sural nerve SNAP amplitude (-5.2 m/s, p < 0.001) and sural nerve
      conduction velocity (-8.2 uV, p < 0.001). In contrast, the least significant
      changes were in peroneal nerve CMAP amplitude (-0.65 mV, p = 0.008). CONCLUSIONS:
      The results of the study demonstrated a progressive increase in the DN prevalence
      over time, in particular its subclinical stages. The long-term poor glycaemic
      control was a determining factor in the rapid DN development. The sensory
      conduction parameters deteriorated faster than the motor parameters. The present
      study is one of few of those in type 1 DM, which in relation to risk factors
      assess not only the presence of neuropathy, but also its severity. The results
      support the necessity of a regular diagnostic search for DN in diabetic children.

PMID- 27028141
TI  - Kinematic characteristics of anterior cruciate ligament deficient knees with
      concomitant meniscus deficiency during ascending stairs.
AB  - It is commonly believed that a torn ACL or a damaged meniscus may be associated
      with altered knee joint movements. The purpose of this study was to measure the
      tibiofemoral kinematics of ACL deficiency with concomitant meniscus deficiency.
      Unilateral knees of 28 ACL deficient participants were studied while ascending
      stairs. Among these patients, 6 had isolated ACL injuries (group I), 8 had
      combined ACL and medial meniscus injuries (group II), 8 had combined ACL and
      lateral meniscus injuries (group III) and 6 had combined ACL and medial-lateral
      meniscus injuries (group IV). Both knees were then scanned during a stair climb
      activity using single fluoroscopic image system. Knee kinematics were measured at
      0 degrees , 5 degrees , 10 degrees , 15 degrees , 30 degrees  and 60 degrees  of
      flexion during ascending stairs. At 0 degrees , 15 degrees  and 30 degrees 
      flexion of the knee, the tibia rotated externally by 13.9 +/- 6.1 degrees ,13.8
      +/- 9.5 degrees  and 15.9 +/- 9.8 degrees  in Group I. Group II and III exhibited
      decreased external rotation from 60 degrees  to full extension. Statistical
      differences were found in 0 degrees , 15 degrees and 30 degrees  of flexion for
      the 2 groups compared with Group I. In general, the tibia showed anterior
      translation with respect to the femur during ascending stairs. It was further
      determined that Group III had larger anterior translation compared with Group IV
      at 0 degrees  and 5 degrees  of flexion (-6.9 +/- 1.7 mm vs. 6.2 +/- 11.3 mm, P =
      0.041; -9.0 +/- 1.8 mm vs. 8.1 +/- 13.4 mm, P = 0.044). During ascending stairs
      the ACL deficient knee with different deficiencies in the meniscus will show
      significantly different kinematics compared with that of uninjured contralateral
      knee. Considering the varying effect of meniscus injuries on knee joint
      kinematics, future studies should concentrate on specific treatment of patients
      with combined ACL and meniscus injuries to protect the joint from abnormal
      kinematics and subsequent postoperative degeneration.

PMID- 27028142
TI  - Impaired gut junctional complexes feature late-treated individuals with
      suboptimal CD4+ T-cell recovery upon virologically suppressive combination
      antiretroviral therapy.
AB  - OBJECTIVE: HIV-infected individuals with incomplete CD4+ T-cell recovery upon
      combination antiretroviral therapy (cART) display high levels of immune
      activation and microbial translocation. However, whether a link exists between
      gut damage and poor immunological reconstitution remains unknown. DESIGN: Cross
      sectional study of the gastrointestinal tract in late cART-treated HIV-infected
      individuals: 15 immunological nonresponders (CD4+ <350 cells/MUl and/or delta
      CD4+ change from baseline <30%); 15 full responders (CD4+ >350 cells/MUl and/or
      delta CD4+ change from baseline >30%). METHODS: We assessed gut structure
      (junctional complex proteins in ileum and colon) and function (small intestine
      permeability/damage and microbial translocation parameters). The composition of
      the fecal microbiome and the size of the HIV reservoir in the gut and peripheral
      blood were investigated as possible mechanisms underlying mucosal impairment.
      RESULTS: Markers of intestinal permeability, damage, systemic inflammation, and
      microbial translocation were comparable in all study individuals, yet the
      expression of junctional complex proteins in gut biopsies was significantly lower
      in HIV-infected patients with incomplete CD4+ restoration and negatively
      correlated with markers of CD4+ reconstitution. Electron microscopy revealed
      dilated intercellular spaces in individuals lacking immunological response to
      cART, yet not in patients displaying CD4+ T-cell recovery. Analysis of the fecal
      microbiome revealed an overall outgrowth of Bacteroides-Prevotella spp. with no
      differences according to CD4+ T-cell reconstitution. Interestingly, HIV
      reservoirs in peripheral CD4+ T cells and intestinal tissue negatively correlated
      with immune recovery. CONCLUSION: These observations establish gut damage and the
      size of the HIV reservoir as features of deficient immunological response to cART
      and provide new elements for interventional strategies in this setting.

PMID- 27028143
TI  - Decreased ovarian reserve in HIV-infected women.
AB  - OBJECTIVE: To evaluate HIV directly or indirectly related altered ovarian
      function, using serum anti-Mullerian hormone (AMH) levels in HIV-infected women
      as compared with seronegative women. DESIGN: We conducted a matched cohort study
      from January 2008 to December 2013 in a tertiary university centre. Two hundred
      and one HIV-infected women requesting assisted reproductive technology and 603
      age and cause of infertility-matched HIV seronegative women were enrolled in this
      study. METHODS: All data were prospectively collected using a semistructured
      questionnaire. Serum AMH levels in HIV-infected women and matched controls were
      compared. To find out the contributing factors to increased serum AMH levels in
      HIV-infected women, a backward multiple linear regression was performed. RESULTS:
      Serum AMH levels were significantly lower in HIV-infected group as compared with
      seronegative controls (3.0 +/- 2.8 vs 3.7 +/- 3.5 ng/ml; respectively, P =
      0.001). Looking for factors associated with altered AMH among HIV-infected women,
      an association has been shown between tubal disease and a further decrease in
      serum AMH levels (2.4 +/- 2.4 vs 3.4 +/- 3.0 ng/ml; respectively, P = 0.011).
      Among HIV-infected women, after multivariate linear regression analysis, we
      showed that increased age, BMI and viral load were associated with decreased
      serum AMH levels whereas in striking contrast an increase in CD4+ cell count was
      associated with an increase of serum AMH levels. CONCLUSION: Serum AMH levels
      were lower in the HIV-infected group than in the control group. Age, BMI, CD4+
      cell count and viral load were the independent contributors affecting serum AMH
      levels among HIV-infected women.

PMID- 27028144
TI  - Thrombopoietin receptor agonists in conjunction with oseltamivir for immune
      thrombocytopenia.

PMID- 27028145
TI  - Recurrent cerebrospinal fluid escape in an HIV-1-infected patient receiving
      antiretroviral therapy.

PMID- 27028146
TI  - Impact of adding raltegravir to antiretroviral regimens in patients with blood
      viral suppression but persistent seminal viral shedding.

PMID- 27028148
TI  - Elucidating the Functional Roles of Spatial Organization in Cross-Membrane Signal
      Transduction by a Hybrid Simulation Method.
AB  - The ligand-binding of membrane receptors on cell surfaces initiates the dynamic
      process of cross-membrane signal transduction. It is an indispensable part of the
      signaling network for cells to communicate with external environments. Recent
      experiments revealed that molecular components in signal transduction are not
      randomly mixed, but spatially organized into distinctive patterns. These
      patterns, such as receptor clustering and ligand oligomerization, lead to very
      different gene expression profiles. However, little is understood about the
      molecular mechanisms and functional impacts of this spatial-temporal regulation
      in cross-membrane signal transduction. In order to tackle this problem, we
      developed a hybrid computational method that decomposes a model of signaling
      network into two simulation modules. The physical process of binding between
      receptors and ligands on cell surfaces are simulated by a diffusion-reaction
      algorithm, while the downstream biochemical reactions are modeled by stochastic
      simulation of Gillespie algorithm. These two processes are coupled together by a
      synchronization framework. Using this method, we tested the dynamics of a simple
      signaling network in which the ligand binding of cell surface receptors triggers
      the phosphorylation of protein kinases, and in turn regulates the expression of
      target genes. We found that spatial aggregation of membrane receptors at cellular
      interfaces is able to either amplify or inhibit downstream signaling outputs,
      depending on the details of clustering mechanism. Moreover, by providing higher
      binding avidity, the co-localization of ligands into multi-valence complex
      modulates signaling in very different ways that are closely related to the
      binding affinity between ligand and receptor. We also found that the temporal
      oscillation of the signaling pathway that is derived from genetic feedback loops
      can be modified by the spatial clustering of membrane receptors. In summary, our
      method demonstrates the functional importance of spatial organization in cross
      membrane signal transduction. The method can be applied to any specific signaling
      pathway in cells.

PMID- 27028147
TI  - Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of
      Carcinogenic Exposure.
AB  - Albumin is a commonly used serum protein for studying human exposure to
      xenobiotic compounds, including therapeutics and environmental pollutants. Often,
      the reactivity of albumin with xenobiotic compounds is studied ex vivo with human
      albumin or plasma/serum samples. Some studies have characterized the reactivity
      of albumin with chemicals in rodent models; however, differences between the
      orthologous peptide sequences of human and rodent albumins can result in the
      formation of different types of chemical-protein adducts with different
      interaction sites or peptide sequences. Our goal is to generate a human albumin
      transgenic mouse model that can be used to establish human protein biomarkers of
      exposure to hazardous xenobiotics for human risk assessment via animal studies.
      We have developed a human albumin transgenic mouse model and characterized the
      genotype and phenotype of the transgenic mice. The presence of the human albumin
      gene in the genome of the model mouse was confirmed by genomic PCR analysis,
      whereas liver-specific expression of the transgenic human albumin mRNA was
      validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses
      indicated that the transgenic human albumin protein is a full-length, mature
      protein, which is less abundant than the endogenous mouse albumin that coexists
      in the serum of the transgenic mouse. The transgenic protein was able to form ex
      vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat.
      This novel human albumin transgenic mouse model will facilitate the development
      and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure
      and/or toxicity in humans.

PMID- 27028149
TI  - Control of Molecule-Metal Interaction by Hydrogen Manipulation in an Organic
      Molecule.
AB  - Free-base porphyrin molecules offer appealing options to tune the interaction
      with their environment via the manipulation of their inner hydrogen atoms and
      molecular conformation. Using scanning tunneling microscopy we show, through a
      systematic study, that the molecular conformation, electronic gap, wave function,
      and molecule-substrate interaction are modified by hydrogen switch or removal.
      Experimental results in combination with ab initio calculations provide an
      understanding of the underlying physical process. 

PMID- 27028150
TI  - Periodontal disease and percentage of calories from fat using national data.
AB  - BACKGROUND AND OBJECTIVE: The association between periodontal disease and
      nutrient intake was examined using linked data from the 2005 National Health and
      Nutrition Survey, the Comprehensive Survey of Living Conditions and the Survey of
      Dental Diseases from the same year 'using linked data from the National Health
      and Nutrition Survey, the Comprehensive Survey of Living Conditions and the
      Survey of Dental Diseases, all from 2005'. There has been increasing focus on the
      importance of nutritional factors in disease in recent years, but very few
      studies in Japan have looked at the association between periodontal disease and
      nutrients. Therefore, in the present study we investigated factors associated
      with periodontal disease, particularly in terms of nutrient intake. MATERIAL AND
      METHODS: Data from 3043 individuals, >= 20 years of age (the original study
      sample comprised 4873 individuals, but those younger than 20 years of age and
      pregnant women were excluded from the present study) were compiled from linked
      responses to these three surveys from the same year. Permission to use the data
      was obtained from the Lifestyle-Related Diseases Control General Affairs Division
      of the Ministry of Health, Labor, and Welfare, Japan. Information including basic
      attributes, family structure, economic status, physical condition, lifestyle
      habits, diet, dental habits, blood data, intake of foods (including the
      categories of food) and nutrient-related information were obtained from the
      linked data. The individual maximum Community Periodontal Index (CPI) was used as
      an index of periodontal disease. Subjects were divided, according to maximum CPI,
      into groups in which CPI = 0-2 or CPI = 3-4, and associations between CPI and
      basic attributes, family structure, economic status, physical condition,
      lifestyle habits, diet, blood data and food intake were analyzed. RESULTS:
      Multivariate analysis revealed that the percentage of calories from fat was a
      nutrient factor associated with periodontal disease, with the percentage of
      calories from fat being significantly lower in the group with advanced
      periodontal disease. CONCLUSION: The results suggest that a low-fat, high
      carbohydrate diet is related to periodontal disease. A more detailed analysis of
      this topic will be conducted in the future using different indices of periodontal
      disease.

PMID- 27028151
TI  - Novel TGFBI mutation p.(Leu558Arg) in a lattice corneal dystrophy patient.

PMID- 27028152
TI  - Comparison of hospital room surface disinfection using a novel ultraviolet
      germicidal irradiation (UVGI) generator.
AB  - The estimated 721,800 hospital acquired infections per year in the United States
      have necessitated development of novel environmental decontamination technologies
      such as ultraviolet germicidal irradiation (UVGI). This study evaluated the
      efficacy of a novel, portable UVGI generator (the TORCH, ChlorDiSys Solutions,
      Inc., Lebanon, NJ) to disinfect surface coupons composed of plastic from a
      bedrail, stainless steel, chrome-plated light switch cover, and a porcelain tile
      that were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) or
      vancomycin-resistant Enterococcus faecalis (VRE). Each surface type was placed at
      6 different sites within a hospital room and treated by 10-min ultraviolet-C
      (UVC) exposures using the TORCH with doses ranging from 0-688 mJ/cm(2) between
      sites. Organism reductions were compared with untreated surface coupons as
      controls. Overall, UVGI significantly reduced MRSA by an average of 4.6 log10
      (GSD: 1.7 log10, 77% inactivation, p < 0.0001) and VRE by an average of 3.9 log10
      (GSD: 1.7 log10, 65% inactivation, p < 0.0001). MRSA on bedrail was reduced
      significantly (p < 0.0001) less than on other surfaces, while VRE was reduced
      significantly less on chrome (p = 0.0004) and stainless steel (p = 0.0012) than
      porcelain tile. Organisms out of direct line of sight of the UVC generator were
      reduced significantly less (p < 0.0001) than those directly in line of sight.
      UVGI was found an effective method to inactivate nosocomial pathogens on surfaces
      evaluated within the hospital environment in direct line of sight of UVGI
      treatment with variation between organism and surface types.

PMID- 27028153
TI  - Molecular determinants of alphavirus neuropathogenesis in mice.
AB  - Alphaviruses are enveloped viruses with a positive-stranded RNA genome, of the
      family Togaviridae. In mammals and birds they are mosquito-transmitted and are of
      veterinary and medical importance. They cause primarily two types of disease:
      encephalitis and polyarthritis. Here we review attempts to understand the
      molecular basis of encephalitis and virulence for the central nervous system
      (CNS) in mouse models. Sindbis virus (SINV) was the first virus to be studied in
      this way. Other viruses analysed are Semliki Forest virus (SFV), Venezuelan
      equine encephalitis virus, Eastern equine encephalitis virus and Western equine
      encephalitis virus. Neurovirulence was found to be associated with damage to
      neurons in the CNS. It mapped mainly to the E2 region of the genome, and to the
      nsP3 gene. Also, avirulent natural isolates of both SINV and SFV have been found
      to have more rapid cleavage of nonstructural proteins due to mutations in the
      nsP1-nsP2 cleavage site. Immune-mediated demyelination for avirulent SFV has been
      shown to be associated with infection of oligodendrocytes. For Chikungunya virus,
      an emerging alphavirus that uncommonly causes encephalitis, analysis of the
      molecular basis of CNS pathogenicity is beginning. Experiments on SINV and SFV
      have indicated that virulence may be related to the resistance of virulent virus
      to interferon action. Although the E2 protein may be involved in tropism for
      neurons and passage across the blood-brain barrier, the role of the nsP3 protein
      during infection of neurons is unknown. More information in these areas may help
      to further explain the neurovirulence of alphaviruses. 

PMID- 27028154
TI  - Structure-based design, synthesis, molecular docking study and biological
      evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with
      anti-oxidant activities.
AB  - A set of 1,2,4-triazine derivatives were designed as cyclooxygenase-2 (COX-2)
      inhibitors. These compounds were synthesized and screened for inhibition of
      cyclooxygenases (COX-1 and COX-2) based on a cellular assay using human whole
      blood (HWB) and lipoxygenase (LOX-15) that are key enzymes in inflammation. The
      results showed that 3-(2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinyl)-5,6-bis(4
      methoxyphenyl)-1,2,4-triazine (G11) was identified as the most potent COX-2
      inhibitor (78%) relative to COX-1 (50%). Ferric reducing anti-oxidant power
      (FRAP) assay revealed that compound G10 possesses the highest anti-oxidant
      activity. The compound G3 with IC50 value of 124 MUM was the most potent compound
      in LOX inhibitory assay. Molecular docking was performed and a good agreement was
      observed between computational and experimental results. 

PMID- 27028155
TI  - The Neuromuscular, Biochemical, and Endocrine Responses to a Single-Session Vs.
      Double-Session Training Day in Elite Athletes.
AB  - Johnston, MJ, Cook, CJ, Drake, D, Costley, L, Johnston, JP, and Kilduff, LP. The
      neuromuscular, biochemical, and endocrine responses to a single-session vs.
      double-session training day in elite athletes. J Strength Cond Res 30(11): 3098
      3106, 2016-The aim of this study was to compare the acute neuromuscular,
      biochemical, and endocrine responses of a training day consisting of a speed
      session only with performing a speed-and-weights training session on the same
      day. Fifteen men who were academy-level rugby players completed 2 protocols in a
      randomized order. The speed-only protocol involved performing 6 maximal effort
      repetitions of 50-m running sprints with 5 minutes of recovery between each
      sprint, whereas the speed-and-weights protocol involved the same sprinting
      session but was followed 2 hours later by a lower-body weights session consisting
      of 4 sets of 5 backsquats and Romanian deadlift at 85% one repetition maximum.
      Testosterone, cortisol, creatine kinase, lactate, and perceived muscle soreness
      were determined immediately before, immediately after, 2 hours after, and 24
      hours after both the protocols. Peak power, relative peak power, jump height, and
      average rate of force development were determined from a countermovement jump
      (CMJ) at the same time points. After 24-hours, muscle soreness was significantly
      higher after the speed-and-weights protocol compared with the speed-only protocol
      (effect size eta = 0.253, F = 4.750, p <= 0.05). There was no significant
      difference between any of the CMJ variables at any of the posttraining time
      points. Likewise, creatine kinase, testosterone, and cortisol were unaffected by
      the addition of a weight-training session. These data indicate that the addition
      of a weight-training session 2 hours after a speed session, whereas increasing
      the perception of fatigue the next day does not result in a difference in
      endocrine response or in neuromuscular capability.

PMID- 27028156
TI  - Acute Cardiopulmonary and Metabolic Responses to High-Intensity Interval Training
      Protocols Using 60 s of Work and 60 s Recovery.
AB  - Rozenek, R, Salassi III, JW, Pinto, NM, and Fleming, JD. Acute cardiopulmonary
      and metabolic responses to high-intensity interval training protocols using 60 s
      of work and 60 s recovery. J Strength Cond Res 30(11): 3014-3023, 2016-Low
      volume, high-intensity interval training (HIIT) consisting of 60 s work and 60 s
      recovery (60 s/60 s) repeated for 10 times has previously been found to produce
      beneficial cardiopulmonary, cellular, and metabolic adaptations in healthy and at
      risk populations. There is currently relatively little information pertaining to
      the acute changes that take place during individual training sessions. The
      purpose of this study was to examine the acute physiological responses to 60 s/60
      s * 10 HIIT protocols using several combinations of work and recovery
      intensities. Eleven healthy adults (mean age +/- SD = 26.0 +/- 5.3 years)
      performed 4 HIIT trials on separate days at varying percentages of peak power
      output that consisted of the following work/recovery intensities: (a) 80% PPO/0%
      PPO (80/0); (b) 80% PPO/50% PPO (80/50); (c) 100% PPO/0% PPO (100/0); and (d)
      100% PPO/50% PPO (100/50). Compared with the other protocols, 100/50 produced
      higher (p <= 0.05) peak, average, and nadir %V[Combining Dot Above]O2peak. Other
      than the nadir values resulting from the 80/0 trial, all trials produced average,
      peak, and nadir %V[Combining Dot Above]O2peak and %HRpeak values that were within
      exercise intensity ranges (~45-90% V[Combining Dot Above]O2max; ~65-90% HRmax)
      recommended by the American College of Sports Medicine for improvement of
      cardiopulmonary function. Similar average HR and peak HR, RPE, blood lactate, and
      %V[Combining Dot Above]O2peak values were produced by 80/50 and 100/0 protocols.
      However, the average %V[Combining Dot Above]O2peak was significantly higher
      (~9.3% absolute) in 80/50. It appeared that use of the 80/0, 80/50, and 100/0
      protocols would be appropriate for individuals who are at the low to moderate end
      of the cardiopulmonary fitness spectrum.

PMID- 27028157
TI  - A trans-Hyponitrite Intermediate in the Reductive Coupling and Deoxygenation of
      Nitric Oxide by a Tricopper-Lewis Acid Complex.
AB  - The reduction of nitric oxide (NO) to nitrous oxide (N2O) is a process relevant
      to biological chemistry as well as to the abatement of certain environmental
      pollutants. One of the proposed key intermediates in NO reduction is hyponitrite
      (N2O2(2-)), the product of reductive coupling of two NO molecules. We report the
      reductive coupling of NO by an yttrium-tricopper complex generating a trans
      hyponitrite moiety supported by two MU-O-bimetallic (Y,Cu) cores, a previously
      unreported coordination mode. Reaction of the hyponitrite species with Bronsted
      acids leads to the generation of N2O, demonstrating the viability of the
      hyponitrite complex as an intermediate in NO reduction to N2O. The additional
      reducing equivalents stored in each tricopper unit are employed in a subsequent
      step for N2O reduction to N2, for an overall (partial) conversion of NO to N2.
      The combination of Lewis acid and multiple redox active metals facilitates this
      four electron conversion via an isolable hyponitrite intermediate. 

PMID- 27028158
TI  - Targeted Population Health Management for Under 55-Year-Olds Qualifying for LTC
      Services.

PMID- 27028159
TI  - Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief
      in Experimental Neuropathy.
AB  - The long-term use of potent analgesics is often needed to treat chronic pain.
      However, it has been greatly hindered by their side effects such as addiction and
      withdrawal reactions. The study seeks to circumvent these drawbacks by taking
      advantage of a multifunctional delivery system based on nanoparticles to target
      on pathological neuroinflammation. A drug delivery system is designed and
      generated using mesoporous silica nanoparticles (MSNs) that are loaded with
      Delta9-THC (Delta9-tetrahydrocannabinol, a cannabinoid) and ARA290 (an
      erythropoietin-derived polypeptide), both of which possess analgesic and anti
      inflammatory functions. The actions of such THC-MSN-ARA290 nanocomplexes depend
      on the enhanced permeability and retention of THC through nanosized carriers, and
      a redox-sensitive release of conjugated ARA290 peptide into the local
      inflammatory milieu. The biosafety and anti-inflammatory effects of the
      nanocomplexes are first evaluated in primary microglia in vitro, and further in a
      mouse model of chronic constriction injury. It is found that the nanocomplexes
      attenuate in vitro and in vivo inflammation, and achieve a sustained relief of
      neuropathic pain in injured animals induced by both thermal hyperalgesia and
      mechanical allodynia. Thus, a nanoparticle-based carrier system can be useful for
      the amelioration of chronic neuropathic pain through combinatorial drug delivery.

PMID- 27028161
TI  - Selective Metal-Free Hydrosilylation of CO2 Catalyzed by Triphenylborane in
      Highly Polar, Aprotic Solvents.
AB  - Triphenylborane (BPh3 ) in highly polar, aprotic solvents catalyzes
      hydrosilylation of CO2 effectively under mild conditions to provide silyl
      formates with high chemoselectivity (>95 %) and without over-reduction. This
      system also promotes reductive hydrosilylation of tertiary amides as well as
      dehydrogenative coupling of silane with alcohols.

PMID- 27028160
TI  - Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk
      Variants, and Shared Genetic Risks.
AB  - IMPORTANCE: Cannabis dependence (CAD) is a serious problem worldwide and is of
      growing importance in the United States because cannabis is increasingly
      available legally. Although genetic factors contribute substantially to CAD risk,
      at present no well-established specific genetic risk factors for CAD have been
      elucidated. OBJECTIVE: To report findings for DSM-IV CAD criteria from
      association analyses performed in large cohorts of African American and European
      American participants from 3 studies of substance use disorder genetics. DESIGN,
      SETTING, AND PARTICIPANTS: This genome-wide association study for DSM-IV CAD
      criterion count was performed in 3 independent substance dependence cohorts (the
      Yale-Penn Study, Study of Addiction: Genetics and Environment [SAGE], and
      International Consortium on the Genetics of Heroin Dependence [ICGHD]). A
      referral sample and volunteers recruited in the community and from substance
      abuse treatment centers included 6000 African American and 8754 European American
      participants, including some from small families. Participants from the Yale-Penn
      Study were recruited from 2000 to 2013. Data were collected for the SAGE trial
      from 1990 to 2007 and for the ICGHD from 2004 to 2009. Data were analyzed from
      January 2, 2013, to November 9, 2015. MAIN OUTCOMES AND MEASURES: Criterion count
      for DSM-IV CAD. RESULTS: Among the 14 754 participants, 7879 were male, 6875 were
      female, and the mean (SD) age was 39.2 (10.2) years. Three independent regions
      with genome-wide significant single-nucleotide polymorphism associations were
      identified, considering the largest possible sample. These included rs143244591
      (beta = 0.54, P = 4.32 * 10-10 for the meta-analysis) in novel antisense
      transcript RP11-206M11.7;rs146091982 (beta = 0.54, P = 1.33 * 10-9 for the meta
      analysis) in the solute carrier family 35 member G1 gene (SLC35G1); and
      rs77378271 (beta = 0.29, P = 2.13 * 10-8 for the meta-analysis) in the CUB and
      Sushi multiple domains 1 gene (CSMD1). Also noted was evidence of genome-level
      pleiotropy between CAD and major depressive disorder and for an association with
      single-nucleotide polymorphisms in genes associated with schizophrenia risk.
      Several of the genes identified have functions related to neuronal calcium
      homeostasis or central nervous system development. CONCLUSIONS AND RELEVANCE:
      These results are the first, to our knowledge, to identify specific CAD risk
      alleles and potential genetic factors contributing to the comorbidity of CAD with
      major depression and schizophrenia.

PMID- 27028162
TI  - Dealing With Uncertainty: Testing Risk- and Ambiguity-Attitude Across
      Adolescence.
AB  - Attitudes to risk (known probabilities) and attitudes to ambiguity (unknown
      probabilities) are separate constructs that influence decision making, but their
      development across adolescence remains elusive. We administered a choice task to
      a wide adolescent age-range (N = 157, 10-25 years) to disentangle risk- and
      ambiguity-attitudes using a model-based approach. Additionally, this task was
      played in a social context, presenting choices from a high risk-taking peer. We
      observed age-related changes in ambiguity-attitude, but not risk-attitude. Also,
      ambiguity-aversion was negatively related to real-life risk taking. Finally, the
      social context influenced only risk-attitudes. These results highlight the
      importance of disentangling risk- and ambiguity-attitudes in adolescent risk
      taking.

PMID- 27028163
TI  - First-principles investigation of methanethiol adsorption and dissociation
      mechanisms on the high-Miller-index vicinal surface Cu(4 1 0).
AB  - In this work, we present detailed investigations of methanethiol adsorption on a
      Cu(4 1 0) surface within the framework of the self-consistent first-principles
      calculations as implemented in the Vienna ab initio simulation package (VASP). In
      particular, the adsorption sites, the surface coverage rate and electronic
      properties have been determined and compared to experimental values. The results
      indicate that the favorable adsorption site in the case of low coverage rate is a
      bridge on the step followed by the hollow site on the terrace. The adsorption
      significantly affects the outermost layer of the surface mainly for a higher
      coverage rate in a (2 * 2) supercell. The nature of the chemisorption process on
      the surface is analyzed by means of the density of states which, combined with
      charge density difference and atomic charge calculations, confirms the ionic
      character of the S-Cu bond. The specific effect of the presence of steps is
      highlighted by comparing the adsorption on the (1 0 0) terrace to the adsorption
      on the extended Cu(1 0 0) surface. Compared to the flat Cu(1 0 0), it is found
      here that while the stability is almost the same at p(2 * 2) coverage, the
      CH3S/Cu(4 1 0) becomes more stable than CH3S/Cu(1 0 0) at c(2 * 2) coverage with
      0.30 eV per molecule. The mechanism of methanethiol dissociation is explored by
      the nudged elastic band method and demonstrates that the most favorable path is
      dissociation followed by migration of hydrogen from the step to its most stable
      position (hollow on the terrace) with energy barriers less than 0.5 eV.

PMID- 27028164
TI  - Hyperpigmentation on face and arms and thyrotoxicosis induced by amiodarone
      treatment.

PMID- 27028165
TI  - Enhancing interprofessional education and practice: Development and
      implementation of a new graduate-level course using the international
      classification of functioning, disability, and health.
AB  - Since the introduction of the World Health Organization's International
      Classification of Functioning, Disability and Health (ICF), there is increasing
      awareness among health professionals to consider a biopsychosocial approach to
      patients' health and functioning. Although diffusion of the ICF as a concept is
      widely recognized, application of the ICF within health education and practice
      requires attention, training, and support. This article describes the development
      and implementation of a new graduate-level course using the ICF to assist health
      professionals and graduate trainees in rehabilitation. The innovation behind this
      course is its focus on application of the ICF in research and practice through a
      combination of peer support and instructor mentorship. The value of the ICF for
      interprofessional education, research, and practice includes promotion of a broad
      perspective to health, application of theory in practice, and enhanced
      communication and collaboration in healthcare. 

PMID- 27028166
TI  - Polyfluorene Electrolytes Interfacial Layer for Efficient Polymer Solar Cells:
      Controllably Interfacial Dipoles by Regulation of Polar Groups.
AB  - The polar groups in the conjugated polyelectrolytes (CPEs) can create the
      favorable dipoles at the electrode/active layer interface, which is critical for
      the CPEs to minimize the interfacial energy barrier in polymer solar cells
      (PSCs). Herein, a series of CPEs based on poly [(9,9-bis(3'-(N,N
      dimethylamino)propyl)-2,7-fluorene)-co-2,7-(9,9-dioctylfluorene)] derivates
      (PFNs) (PFN30, PFN50, PFN70, and PFN100) with different mole ratio of polar
      groups (-N(C2H5)2) were designed and synthesized to investigate the effect of the
      numbers of polar groups on the interfacial dipoles. Controllably interfacial
      dipoles could be readily achieved by only tuning the numbers of -N(C2H5)2 in
      PFNs, as revealed by the work function of the PFNs modified ITO gradually reduced
      as the loadings of the -N(C2H5)2 increased. In addition, increasing the numbers
      of -N(C2H5)2 in PFNs were also favorable for developing the smooth and
      homogeneous morphology of the active layer. As a result, the content of the polar
      amine in the PFNs exerted great influence on the performance of polymer solar
      cells. Increasing the numbers of the pendent -N(C2H5)2 could effectively improve
      the power conversion efficiency (PCE) of the devices. Among these PFNs, PFN100
      with the highest content of -N(C2H5)2 polar groups delivered the device with the
      best PCE of 3.27%. It indicates tailoring the content of the polar groups in the
      CPEs interlayer is a facial and promising approach for interfacial engineering to
      developing high performance PSCs. 

PMID- 27028167
TI  - Antimicrobial Susceptibility and Plasmid Replicon Typing of Salmonella enterica
      Serovar Kentucky Isolates Recovered from Broilers.
AB  - Salmonella Kentucky has become the predominant serovar recovered from broilers
      slaughtered in the United States, and the prevalence of antimicrobial resistance
      (AMR) has increased dramatically in this serovar. Relationships between AMR,
      genotype, and plasmid replicon types were characterized for 600 Salmonella
      Kentucky isolates recovered from chicken carcasses from 2004 to 2013. Pulsed
      field gel electrophoresis cluster analysis revealed 112 unique types sharing 79%
      similarity. Over half of the isolates studies were assigned to two large clusters
      (unique restriction patterns) consisting of 190 (A) and 151 (B) isolates. The
      remaining (n = 259) more diverse isolates (110 unique patterns) shall be
      designated cluster C for discussion. Clusters A had significantly more (p < 0.05)
      isolates resistant to streptomycin (68.4%) and tetracycline (91.6%) compared to
      cluster C (50.6% and 40.9% to streptomycin and tetracycline, respectively) or
      cluster B, which had the least (p < 0.05) resistance (11.9% and 13.2% to
      streptomycin and tetracycline, respectively). In addition, there was segregation
      of plasmid replicon types among clusters. Cluster A had significantly more (p <
      0.05) replicon type FIB (90.5%) compared to cluster C (37.1%), which had
      significantly more compared to cluster B (10.6%). Cluster B had significantly
      more (p < 0.05) replicon type I1 (87.4%) compared to cluster C (68.7%), which had
      significantly more (p < 0.05) compared to cluster A (32.6%). Cluster C harbored
      significantly more (p < 0.05) HI2 replicon type (18.1%) compared to clonal
      clusters A (1.6%) or B (1.3%). The prevalence of plasmid replicon type A/C did
      not differ among clusters (A, 0.5%; B, 2.0%; C, 0.4%). Both streptomycin and
      tetracycline resistance were significantly linked (p < 0.05) to plasmid replicon
      type FIB. In addition, replicon type HI2 was also significantly linked (p < 0.05)
      to streptomycin resistance. We conclude that the dramatic increase in
      streptomycin and tetracycline resistance among Salmonella Kentucky isolated from
      poultry is due to the expansion of strains harboring plasmid replicon types FIB
      and HI2.

PMID- 27028168
TI  - Neuropsychological and neuroimaging underpinnings of schizoaffective disorder: a
      systematic review.
AB  - OBJECTIVES: The neurobiological basis and nosological status of schizoaffective
      disorder remains elusive and controversial. This study provides a systematic
      review of neurocognitive and neuroimaging findings in the disorder. METHODS: A
      comprehensive literature search was conducted via PubMed, ScienceDirect, Scopus
      and Web of Knowledge (from 1949 to 31st March 2015) using the keyword
      'schizoaffective disorder' and any of the following terms: 'neuropsychology',
      'cognition', 'structural neuroimaging', 'functional neuroimaging', 'multimodal',
      'DTI' and 'VBM'. Only studies that explicitly examined a well defined sample, or
      subsample, of patients with schizoaffective disorder were included. RESULTS:
      Twenty-two of 43 neuropsychological and 19 of 51 neuroimaging articles fulfilled
      inclusion criteria. We found a general trend towards schizophrenia and
      schizoaffective disorder being related to worse cognitive performance than
      bipolar disorder. Grey matter volume loss in schizoaffective disorder is also
      more comparable to schizophrenia than to bipolar disorder which seems consistent
      across further neuroimaging techniques. CONCLUSIONS: Neurocognitive and
      neuroimaging abnormalities in schizoaffective disorder resemble more
      schizophrenia than bipolar disorder. This is suggestive for schizoaffective
      disorder being a subtype of schizophrenia or being part of the continuum spectrum
      model of psychosis, with schizoaffective disorder being more skewed towards
      schizophrenia than bipolar disorder.

PMID- 27028169
TI  - Moral judgment in episodic amnesia.
AB  - To investigate the role of episodic thought about the past and future in moral
      judgment, we administered a well-established moral judgment battery to
      individuals with hippocampal damage and deficits in episodic thought (insert
      Greene et al. 2001). Healthy controls select deontological answers in high
      conflict moral scenarios more frequently when they vividly imagine themselves in
      the scenarios than when they imagine scenarios abstractly, at some personal
      remove. If this bias is mediated by episodic thought, individuals with deficits
      in episodic thought should not exhibit this effect. We report that individuals
      with deficits in episodic memory and future thought make moral judgments and
      exhibit the biasing effect of vivid, personal imaginings on moral judgment. These
      results strongly suggest that the biasing effect of vivid personal imagining on
      moral judgment is not due to episodic thought about the past and future. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27028170
TI  - Intensity-modulated radiotherapy reduces toxicity with similar biochemical
      control compared with 3-dimensional conformal radiotherapy for prostate cancer: A
      randomized clinical trial.
AB  - BACKGROUND: The objective of this article was to report the results from a
      randomized clinical trial comparing intensity-modulated radiotherapy (IMRT) with
      3-dimensonal conformal radiotherapy (3DCRT) for the treatment of prostate cancer
      on a hypofractionated schedule. METHODS: The authors randomly assigned 215 men
      who had localized prostate cancer to receive hypofractionated radiotherapy to a
      total dose of 70 grays (Gy) in 25 fractions (at 2.8 Gy per fraction) using either
      IMRT or 3DCRT. Acute and late gastrointestinal (GI) and genitourinary (GU)
      toxicity were prospectively evaluated according to modified Radiation Therapy
      Oncology Group criteria. Biochemical control was defined according to the Phoenix
      criteria (prostate-specific antigen nadir + 2 ng/mL). RESULTS: In total, 215
      patients were enrolled in the IMRT group (n = 109) or the 3DCRT group (n = 106).
      The 3DCRT arm had a 27% rate of grade >= 2 acute GU toxicity compared with a 9%
      rate in the IMRT arm (P = .001) and a 24% rate of grade >= 2 acute GI toxicity
      compared with a 7% rate in the IMRT arm (P = .001). The maximal rate of grade >=2
      late GU toxicity during the entire period of follow-up was 3.7% in the IMRT group
      versus 12.3% in the 3DCRT group (P = .02). The maximal rate of grade >=2 late GI
      toxicity during the entire follow-up was 6.4% in the IMRT group versus 21.7% in
      the 3DCRT group (P = .001). The 5-year rate of freedom from biochemical failure
      was 95.4% in the IMRT arm and 94.3% in the 3DCRT arm (P = .678). CONCLUSIONS:
      IMRT reduced the delivery of significant radiation doses to the bladder and
      rectum using a similar target volume. This dosimetric advantage resulted in a
      lower rate of acute/late grade >= 2 GI and GU toxicity for IMRT compared with
      3DCRT. Cancer 2016;122:2004-11. (c) 2016 American Cancer Society.

PMID- 27028171
TI  - Preface.
AB  - The elderly population is increasing worldwide. Never before in history have
      there been so many persons aged 60 years or older. This has multiple consequences
      and challenges for health systems and governments. Therefore, the promotion of
      research on aging is imperative, not only from a biological viewpoint but also
      from social, economic, and political standpoints. A better understanding of these
      phenomena will allow the formulation of new recommendations focused on the aging
      population and based on a solid scientific background, far from obsolete
      stereotypes. 

PMID- 27028172
TI  - Biology of Healthy Aging and Longevity.
AB  - As human life expectancy is prolonged, age-related diseases are thriving. Aging
      is a complex multifactorial process of molecular and cellular decline that
      affects tissue function over time, rendering organisms frail and susceptible to
      disease and death. Over the last decades, a growing body of scientific literature
      across different biological models, ranging from yeast, worms, flies, and mice to
      primates, humans and other long-lived animals, has contributed greatly towards
      identifying conserved biological mechanisms that ward off structural and
      functional deterioration within living systems. Collectively, these data offer
      powerful insights into healthy aging and longevity. For example, molecular
      integrity of the genome, telomere length, epigenetic landscape stability, and
      protein homeostasis are all features linked to "youthful" states. These molecular
      hallmarks underlie cellular functions associated with aging like mitochondrial
      fitness, nutrient sensing, efficient intercellular communication, stem cell
      renewal, and regenerative capacity in tissues. At present, calorie restriction
      remains the most robust strategy for extending health and lifespan in most
      biological models tested. Thus, pathways that mediate the beneficial effects of
      calorie restriction by integrating metabolic signals to aging processes have
      received major attention, such as insulin/insulin growth factor-1, sirtuins,
      mammalian target of rapamycin, and 5' adenosine monophosphate-activated protein
      kinase. Consequently, small-molecule targets of these pathways have emerged in
      the impetuous search for calorie restriction mimetics, of which resveratrol,
      metformin, and rapamycin are the most extensively studied. A comprehensive
      understanding of the molecular and cellular mechanisms that underlie age-related
      deterioration and repair, and how these pathways interconnect, remains a major
      challenge for uncovering interventions to slow human aging while extending
      molecular and physiological youthfulness, vitality, and health. This review
      summarizes key molecular mechanisms underlying the biology of healthy aging and
      longevity. 

PMID- 27028173
TI  - Cancer and Aging: A Complex Biological Association.
AB  - Cancer is one of the leading causes of death in both developing and developed
      countries. It is also a particularly significant health problem in older
      populations since half of all malignancies occur in patients aged 70 years or
      older. Cancer is a disease of aging, and as such there is a strong biological
      association between the mechanisms of aging and carcinogenesis. During the past
      few decades, mechanisms of aging exerting pro- and anti-oncogenic effects have
      been described, and the role of these mechanisms in cancer treatment and
      prognosis is currently being investigated. In this review we describe the
      different theories of aging and the evidence on the biological link between these
      mechanisms and carcinogenesis. Additionally, we review the implications of the
      biology of aging on the treatment and prognosis of older adults with cancer, and
      the opportunities for translational research into biomarkers of aging in this
      patient population. 

PMID- 27028174
TI  - Frailty and Vascular Cognitive Impairment: Mechanisms Behind the Link.
AB  - The relationship between frailty and cognitive impairment has been recognized for
      decades, but it was not until a few years ago that the interest in this
      relationship increased and is now being understood. Epidemiological evidence
      suggests that physical frailty may be linked to cognitive impairment since both
      conditions share pathophysiological mechanisms at the cellular and systemic
      levels. Aging itself promotes multiple vascular changes, making the brain
      susceptible to cognitive decline through mechanisms such as thinning of blood
      vessels, increased collagen accumulation, rupture of the blood-brain barrier,
      inflammation, and oxidative damage. The prevalence of frailty and cognitive
      decline increases as individuals become older, and cognitive impairment
      attributable to cerebrovascular disease has become a major public health problem
      since vascular dementia is now the second most common subtype of dementia.
      However, full understanding of the mechanisms underlying the relationship between
      frailty and vascular cognitive impairment remains fragmented. This review
      examines the link between frailty and vascular cognitive decline and also
      explores the role of vascular changes in the genesis of both conditions. 

PMID- 27028175
TI  - Epidemiology of Cognitive Aging in the Oldest Old.
AB  - The proportion of persons aged 85 and over, the so-called "oldest old", is
      increasing dramatically worldwide. While a quarter of this population is affected
      by dementia, little is known about the specific features of cognitive functioning
      in the oldest old. In the presence of clinical specificities such as numerous
      comorbidities, multi-medication and visual and/or auditory loss, which are very
      frequent in extreme old age, neuropsychological assessment can be particularly
      challenging. This article presents an overview of the epidemiology of cognitive
      functioning in the oldest old, and discusses the issues regarding
      neuropsychological assessment and dementia in this specific elderly population. 

PMID- 27028176
TI  - The Role of Neuroinflammation in Age-Related Dementias.
AB  - The most common dementias such as Alzheimer's disease, vascular dementia, Lewy
      body dementia, and frontotemporal dementia are associated with a decline in
      cognitive and social abilities. Although the molecular mechanisms of tissue
      damage in these dementias are not completely understood, these neurodegenerative
      illnesses share certain alterations such as neuroinflammation and gliosis.
      Increasing evidence suggests that microgliosis and astrogliosis play a key role
      in neuroinflammation observed in these dementias. Here we provide an overview of
      the participation of microglia and astrocytes in the neuroinflammatory response
      in common dementias. 

PMID- 27028178
TI  - Statistical reviewing: constructive criticism towards reproducible research.

PMID- 27028179
TI  - Social Media Editor: what is it all about?

PMID- 27028180
TI  - De novo exonic deletion of KDM6A in a Chinese girl with Kabuki syndrome: A case
      report and brief literature review.
AB  - Kabuki syndrome (KS) is a rare condition with multiple congenital anomalies and
      mental retardation. Exonic deletions, disrupting the lysine (K)-specific
      demethylase 6A (KDM6A) gene have been demonstrated as rare cause of KS. Here, we
      report a de novo 227-kb deletion in chromosome Xp11.3 of a 7-year-old Chinese
      girl with KS. Besides the symptoms of KS, the patient also presented with skin
      allergic manifestations, which were considered to be a new, rare feature of the
      phenotypic spectrum. The deletion includes the upstream region and exons 1-2 of
      KDM6A and potentially causes haploinsuffiency of the gene. We also discuss the
      mutation spectrum of KDM6A and clinical variability of patients with KDM6A
      deletion through a literature review. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028181
TI  - Risk Practices in the Era of Smartphone Apps for Meeting Partners: A Cross
      Sectional Study Among Men Who Have Sex with Men in Melbourne, Australia.

PMID- 27028182
TI  - Egocentric Network and Condom Use Among Mid-Age Female Sex Workers in China: A
      Multilevel Modeling Analysis.
AB  - The epidemics of sexually transmitted infections (STIs) have spread among older
      adults in the world, including China. This study addresses the deficiency of
      studies about the multiple contextual influences on condom use among mid-age
      female sex workers (FSWs) over 35 years old. A combination of an egocentric
      network design and multilevel modeling was used to investigate factors of condom
      use over mid-age FSWs (egos) particular relationships with sexual partners
      (alters). Of the 1245 mid-age FSWs interviewed, 73% (907) reported having at
      least one sexual partner who would provide social support to egos. This generated
      a total of 1300 ego-alter sex ties in egos' support networks. Condoms were
      consistently used among one-third of sex ties. At the ego level, condoms were
      more likely to be used consistently if egos received a middle school education or
      above, had stronger perceived behavioral control for condom use, or consistently
      used condoms with other sex clients who were not in their support networks. At
      the alter level, condoms were not consistently used over spousal ties compared to
      other ties. Condoms were less likely to be used among alters whom ego trusted and
      provided emotional support. Cross-level factors (egos' attitudes toward condom
      use and emotional support from alters) documented a significant positive
      interaction on consistent condom use. Given the low frequency of condom use,
      future interventions should focus on mid-age FSWs and their partners within and
      beyond their support networks. 

PMID- 27028183
TI  - Using a Mobile Health Intervention to Support HIV Treatment Adherence and
      Retention Among Patients at Risk for Disengaging with Care.
AB  - Less than half of the 1.2 million HIV-infected individuals in the United States
      are in consistent medical care, with only a third receiving treatment resulting
      in viral suppression. Novel interventions to improve engagement are necessary to
      ensure medical adherence, improve long-term outcomes, and reduce HIV
      transmission. Mobile health (mHealth) strategies including cell phone and text
      messaging have shown success in the developing world for medical adherence, yet
      mHealth interventions have not been developed and evaluated to improve retention
      in HIV care in the United States. We conducted a 6-month pilot study
      investigating the use of a clinic-based bi-directional texting intervention to
      enhance engagement in HIV care among those with higher risk of loss to follow up,
      including those with a recent HIV diagnosis or those re-engaging in HIV care at a
      large urban clinic in New England. 

PMID- 27028184
TI  - An Index of Multiple Psychosocial, Syndemic Conditions Is Associated with
      Antiretroviral Medication Adherence Among HIV-Positive Youth.
AB  - Medication adherence among HIV-infected individuals is critical to limit disease
      progression and onward transmission. Evidence indicates that among youth living
      with HIV (YLH), adherence is suboptimal and related to co-morbid psychosocial
      conditions. Cross-sectional data from 212 YLH, ages 16-29, collected between 2011
      2014 in Chicago were analyzed to assess the relationship of multiple psychosocial
      conditions (e.g., depressive symptoms, anxiety symptoms, moderate/heavy marijuana
      use, moderate/heavy alcohol use, HIV-related stigma) to ART adherence (i.e., a
      "syndemic.") Adherence was regressed on an index of increasing numbers of
      psychosocial conditions, controlling for demographic and treatment factors as
      well as enrollment site. The mean age of participants was 24, 89% were male, 87%
      black, and 91% behaviorally infected. Psychosocial conditions were prevalent,
      including 38% and 34% with high depressive and anxiety symptoms, respectively,
      54% and 25% with a moderate/high level of marijuana and alcohol use,
      respectively, and 46% reporting high HIV-related stigma. In regression analysis,
      the likelihood of ART adherence decreased with the number of syndemic conditions
      (linear dose response, p = 0.02) as did the odds of viral load suppression (p =
      0.008). Interventions to address these conditions in concert with biomedical
      treatment as prevention for YLH are needed. 

PMID- 27028185
TI  - Corneal Higher-Order Aberrations of the Anterior Surface, Posterior Surface, and
      Total Cornea After SMILE, FS-LASIK, and FLEx Surgeries.
AB  - OBJECTIVES: To investigate the corneal higher-order aberrations (HOAs) of the
      anterior surface, posterior surface, and total cornea after small incision
      lenticule extraction (SMILE) and compare the results using femtosecond laser
      assisted in situ keratomileusis (FS-LASIK) and femtosecond laser lenticule
      extraction (FLEx). METHODS: This study included 160 eyes in total; 73 eyes
      underwent SMILE, 52 eyes underwent FS-LASIK, and 35 eyes underwent FLEx surgery.
      Corneal HOAs of the anterior surface, posterior surface, and total cornea were
      evaluated using a Scheimpflug camera over 6-mm diameter preoperatively and 3
      months postoperatively. RESULTS: The anterior and total corneal HOAs
      significantly increased after SMILE, FS-LASIK, and FLEx surgeries, especially the
      spherical aberration and coma, whereas most posterior corneal HOAs remained
      unchanged. The SMILE procedure induced significantly lower anterior corneal and
      total corneal spherical aberration and third to eighth HOAs compared with FLEx
      surgery (P<0.01). FLEx surgery induced higher posterior corneal coma than SMILE
      (P=0.013) and FS-LASIK (P<0.001) surgeries. CONCLUSIONS: SMILE, FS-LASIK, and
      FLEx surgeries mainly induced coma and spherical aberrations in the anterior
      surface and total cornea. The SMILE procedure induced less spherical aberration
      of the anterior cornea and total cornea than FLEx surgery. The posterior corneal
      spherical aberration significantly increased after FS-LASIK surgery. The SMILE
      procedure seems to have fewer effects on posterior corneal coma compared with the
      FLEx procedure.

PMID- 27028186
TI  - Report on the Conference on Transposition and Genome Engineering 2015 (TGE 2015):
      advancing cutting-edge genomics technology in the ancient city of Nara.
AB  - From November 17 to 20 in 2015, the Conference on Transposition and Genome
      Engineering 2015 (TGE 2015) was held at Nara Kasugano International Forum-IRAKA
      in Nara, Japan, located at the center of Nara Park. All of the presentations were
      carried out at Nohgaku hall in Nara Kasugano International Forum-IRAKA.
      Participation totaled 148 persons (30 international, 118 domestic), who were able
      to engage in lively scientific discussions over the 4-day period. The guest
      speaker list consisted of many top-notch international researchers, an
      achievement for which the conference received praise from the attendees. There
      were 36 oral presentations including the keynote lecture (22 presentations from
      guest speakers, complemented with 14 selected from abstract submissions).
      Additionally, there were 46 poster presentations. The conference uniquely
      combined research mainly from two different genomics approaches: (i) transposon
      technology allowing random genomic integration followed by gene discovery-related
      phenotypes and (ii) genome editing technology with designer nuclease allowing
      precise modification of a gene-of-interest. 

PMID- 27028187
TI  - Prevalence of Palliative Patients with Cancer Treatment and High Levels of
      Discomfort in a French Cancer Center: Is There a Paradox?

PMID- 27028188
TI  - Cumulative effects of volcanic ash on the food preferences of two Orthopteran
      species.
AB  - Inert dusts are an early form of insecticide which is still in use. One of the
      most common inert dusts is volcanic ash. In order to study the reaction of
      rangeland grasshoppers, Dichroplus vittigerum (Acrididae) and a katydid, Burgilis
      mendosensis (Phaneropteridae), to the presence of volcanic ash in their food
      sources and how this reaction changed as a function of time, we conducted paired
      preference tests between clean leaves of their preferred host plant and leaves
      exposed to volcanic ash of different grain size. The behavioral response was
      measured as the rating on the Thurstonian preference scale of leaves with ash in
      relation to clean leaves. The results showed that the avoidance of volcanic ash
      increased as a function of time in both species. Both species studied are
      occasionally exposed to volcanic activity, and come from an area in which a
      volcanic eruption had recently occurred. As their populations did not decrease
      after the ash fall, we propose that some behavioral responses such as avoidance
      of places with ash, works as tolerance mechanism to inert dusts exposure.

PMID- 27028189
TI  - Glyphosate and aminomethylphosphonic acid chronic risk assessment for soil biota.
AB  - Glyphosate is a broad-spectrum herbicide used widely in agriculture,
      horticulture, private gardens, and public infrastructure, where it is applied to
      areas such as roadsides, railway tracks, and parks to control the growth of
      weeds. The exposure risk from glyphosate and the primary soil metabolite
      aminomethylphosphonic acid (AMPA) on representative species of earthworms,
      springtails, and predatory soil mites and the effects on nitrogen-transformation
      processes by soil microorganisms were assessed under laboratory conditions based
      on internationally recognized guidelines. For earthworms, the reproductive no
      observed-effect concentration (NOEC) was 472.8 mg glyphosate acid equivalent
      (a.e.)/kg dry soil, which was the highest concentration tested, and 198.1 mg/kg
      dry soil for AMPA. For predatory mites, the reproductive NOEC was 472.8 mg
      a.e./kg dry soil for glyphosate and 320 mg/kg dry soil for AMPA, the highest
      concentrations tested. For springtails, the reproductive NOEC was 472.8 mg
      a.e./kg dry soil for glyphosate and 315 mg/kg dry soil for AMPA, the highest
      concentrations tested. Soil nitrogen-transformation processes were unaffected by
      glyphosate and AMPA at 33.1 mg a.e./kg soil and 160 mg/kg soil, respectively.
      Comparison of these endpoints with worst-case soil concentrations expected for
      glyphosate (6.62 mg a.e./kg dry soil) and AMPA (6.18 mg/kg dry soil) for annual
      applications at the highest annual rate of 4.32 kg a.e./ha indicate very low
      likelihood of adverse effects on soil biota. Environ Toxicol Chem 2016;35:2742
      2752. (c) 2016 The Authors. Environmental Toxicology and Chemistry Published by
      Wiley Periodicals, Inc. on behalf of SETAC.

PMID- 27028190
TI  - Initial Use of High-Dose Anticholinergics Combined with Alpha-Blockers for Male
      Lower Urinary Tract Symptoms with Overactive Bladder: A Prospective, Randomized
      Preliminary Study.
AB  - OBJECTIVES: To evaluate the clinical efficacy of initial combined treatment of
      alpha-blocker plus dose-dependent anticholinergic agent compared to the alpha
      blocker monotherapy in benign prostatic hyperplasia patients with overactive
      bladder. METHODS: Male lower urinary tract symptoms (LUTS) patients with
      International Prostate Symptom Score (IPSS) of 8 or higher, total overactive
      bladder Symptom Score (OABSS) of 3 or higher, and 2 points or higher in the OABSS
      questionnaire number 2 were enrolled. Eligible subjects (total n = 146) were
      randomly assigned to receive tamsulosin 0.2 mg (Group I, n = 44), tamsulosin 0.2
      mg plus solifenacin 5 mg (Group II, n = 55), or tamsulosin 0.2 mg plus
      solifenacin 10 mg (Group III, n = 47) for 12 weeks. Efficacy and safety
      assessments for each group were done using detailed questionnaires, and
      evaluating urinary parameters such as maximal urinary flow rate (Qmax) and
      postvoid residual volume (PVR) at 4 and 12 weeks. RESULTS: Groups II and III
      (combined use of tamsulosin and solifenacin) showed significant improvement in
      storage symptoms compared to group I (tamsulosin monotherapy), as reflected by
      IPSS storage subscore and OABSS (P < 0.05). Dry mouth developed in four (7%) and
      eight (17%) cases in group II and III, respectively, so that one (2%) and three
      (6%) cases dropped out in group II and III, respectively. Two cases (4%) of AUR
      developed in group III, and one of them was withdrawn (2%) from the study.
      CONCLUSIONS: Initial combined treatment of tamsulosin plus solifenacin for men
      with LUTS improves storage symptoms significantly, but dose modification is
      necessary to prevent adverse events.

PMID- 27028192
TI  - miR-410 suppresses the expression of interleukin-6 as well as renal fibrosis in
      the pathogenesis of lupus nephritis.
AB  - Lupus nephritis (LN) is a highly complex autoimmune disease caused by systemic
      lupus erythematosus (SLE). MicroRNAs (miRNAs) play a vital role in the
      pathogenesis of SLE. Previously, a total of 29 miRNAs were identified to be down
      regulated in SLE patients, in which miR-410 was likely to be involved in the
      signalling transduction pathways in regulating the pathogenesis of SLE. The
      purpose of this study was to investigate the role of miR-410 in LN and to find
      out whether miR-410 regulates the expression of interleukin (IL)-6 and fibrosis
      in LN. It was found that the expression level of miR-410 in kidney tissue of
      MRL/lpr mice was decreased compared to that in BALB/C mice, whereas the level of
      IL-6 was overexpressed in MRL/lpr mice. Luciferase assay showed that miR-410
      binds directly to the 3' untranslated region (UTR) of IL-6, with the results
      showing that overexpression of miR-410 significantly decreased the expression
      level of IL-6 in SV40MES13 cells. Moreover, overexpression of miR-410
      significantly reduced the expression levels of fibrosis factors such as
      transforming growth factor-beta1 (TGF-beta1) and collagen I/III in SV40MES13
      cells; Inhibition of the expression of miR-410 with miR-410 inhibitor resulted in
      increased levels of IL-6 as well as fibrosis factors. The results identify that
      miR-410, as a novel and critical factor in the pathogenesis of LN, decreases IL-6
      expression by binding directly to the 3'UTR and suppresses fibrosis through down
      regulation of TGF-beta1 in SV40MES13 cells. Our study brings new insight into
      understanding the complex mechanisms involved in the pathogenesis of lupus
      disease.

PMID- 27028191
TI  - Feeling of Pleasure to High-Intensity Interval Exercise Is Dependent of the
      Number of Work Bouts and Physical Activity Status.
AB  - OBJECTIVES: To examine the affective responses during a single bout of a low
      volume HIIE in active and insufficiently active men. MATERIALS AND METHODS: Fifty
      eight men (aged 25.3 +/- 3.6 years) volunteered to participate in this study: i)
      active (n = 29) and ii) insufficiently active (n = 29). Each subject undertook i)
      initial screening and physical evaluation, ii) maximal exercise test, and iii) a
      single bout of a low-volume HIIE. The HIIE protocol consisted of 10 x 60s work
      bouts at 90% of maximal treadmill velocity (MTV) interspersed with 60s of active
      recovery at 30% of MTV. Affective responses (Feeling Scale, -5/+5), rating of
      perceived exertion (Borg's RPE, 6-20), and heart rate (HR) were recorded during
      the last 10s of each work bout. A two-factor mixed-model repeated measures ANOVA,
      independent-samples t test, and chi-squared test were used to data analysis.
      RESULTS: There were similar positive affective responses to the first three work
      bouts between insufficiently active and active men (p > 0.05). However,
      insufficiently active group displayed lower affective responses over time (work
      bout 4 to 10) than the active group (p < 0.01). Also, the insufficiently active
      group displayed lower values of mean, lowest, and highest affective response, as
      well as lower values of affective response at the highest RPE than the active
      group (p < 0.001). There were no differences in the RPE and HR between the groups
      (p > 0.05). CONCLUSIONS: Insufficiently active and active men report feelings of
      pleasure to few work bouts (i.e., 3-4) during low-volume HIIE, while the
      affective responses become more unpleasant over time for insufficiently active
      subjects. Investigations on the effects of low-volume HIIE protocols including a
      fewer number of work bouts on health status and fitness of less active subjects
      would be interesting, especially in the first training weeks.

PMID- 27028194
TI  - Monocyte subsets and monocyte-platelet aggregates: implications in predicting
      septic mortality among surgical critical illness patients.
AB  - BACKGROUND: Monocyte subsets and monocyte-platelet aggregates (MPAs) play
      important roles in inflammation. AIM: To evaluate the association between the
      three human monocyte subsets and their contributions to MPAs and mortality among
      septic patients. METHODS: Consecutive septic patients were enrolled in. Age- and
      gender-matched nonseptic patients were recruited as control patients. Monocyte
      subsets and monocyte-platelet aggregates were determined by flow cytometric
      analysis. RESULTS: Elevated percentage of MPAs (MPAs%) was associated with an
      increased risk of mortality. CONCLUSIONS: This study demonstrated increased MPAs%
      enables the identification of a group of septic patients at high risk of death.

PMID- 27028196
TI  - Herniation of the Cerebral Gyrus Into the Giant Arachnoid Granulation in a Child
      With Intermittent Headache.

PMID- 27028195
TI  - DNA-Based Taxonomy in Ecologically Versatile Microalgae: A Re-Evaluation of the
      Species Concept within the Coccoid Green Algal Genus Coccomyxa (Trebouxiophyceae,
      Chlorophyta).
AB  - Coccomyxa is a genus of unicellular green algae of the class Trebouxiophyceae,
      well known for its cosmopolitan distribution and great ecological amplitude. The
      taxonomy of this genus has long been problematic, due to reliance on badly
      defined and environmentally variable morphological characters. In this study,
      based on the discovery of a new species from an extreme habitat, we reassess
      species circumscription in Coccomyxa, a unicellular genus of the class
      Trebouxiophyceae, using a combination of ecological and DNA sequence data
      (analyzed with three different methods of algorithmic species delineation). Our
      results are compared with those of a recent integrative study of Darienko and
      colleagues that reassessed the taxonomy of Coccomyxa, recognizing 7 species in
      the genus. Expanding the dataset from 43 to 61 sequences (SSU + ITS rDNA)
      resulted in a different delimitation, supporting the recognition of a higher
      number of species (24 to 27 depending on the analysis used, with the 27-species
      scenario receiving the strongest support). Among these, C. melkonianii sp. nov.
      is described from material isolated from a river highly polluted by heavy metals
      (Rio Irvi, Sardinia, Italy). Analyses performed on ecological characters detected
      a significant phylogenetic signal in six different characters. We conclude that
      the 27-species scenario is presently the most realistic for Coccomyxa and we
      suggest that well-supported lineages distinguishable by ecological preferences
      should be recognized as different species in this genus. We also recommend that
      for microbial lineages in which the overall diversity is unknown and taxon
      sampling is sparse, as is often the case for green microalgae, the results of
      analyses for algorithmic DNA-based species delimitation should be interpreted
      with extreme caution. 

PMID- 27028197
TI  - National survey data can be used to measure trends in population alcohol
      consumption in Australia.
AB  - OBJECTIVES: To assess the accuracy of the National Drug Strategy Household Survey
      (NDSHS) at capturing trends in alcohol consumption at the population level, using
      apparent per capita alcohol consumption as a benchmark. METHODS: Data was from
      five waves of the NDSHS (2001-2013), with estimates of per capita alcohol
      consumption derived from the detailed graduated frequency alcohol questions.
      Trends are compared with per capita measures, and trends in both series compared.
      Further analyses explore whether recent trends in consumption are consistent
      across age groups. RESULTS: The NDSHS survey estimates still track apparent
      consumption well, which increases between 2001 and 2007 and then declines to
      2013. Since 2007, survey estimates show a 10.5% decline in per capita alcohol
      consumption, compared with 8.9% in ABS data. Two-thirds of the decline came from
      reductions in drinking among respondents under 30. CONCLUSIONS: NDSHS data
      provide reasonably accurate estimates of trends in Australian population alcohol
      consumption. Survey data are critical to understanding the composition of
      overarching trends, with these analyses demonstrating substantial variation by
      age. IMPLICATIONS: Survey data are a crucial tool in monitoring Australian
      alcohol consumption, despite their inherent limitations.

PMID- 27028198
TI  - Racial and Ethnic Differences in Acute Coronary Syndrome and Myocardial
      Infarction Within the United States: From Demographics to Outcomes.
AB  - In the United States, different races, ethnicities, and their subgroups
      experience disparities regarding acute coronary syndrome (ACS) and myocardial
      infarction (MI). This review highlights these differences across 4 stages that
      comprise the ACS/MI narrative: (1) patient demographics, (2) patient
      comorbidities and health risks, (3) treatments and their delays, and (4)
      outcomes. Overall, black and Hispanic ACS/MI patients are more likely to present
      with comorbidities, experience longer delays before treatment, and suffer worse
      outcomes when compared with non-Hispanic white patients. More specifically,
      across the studies analyzed, black and Hispanic ACS/MI patients were consistently
      more likely to be younger or female, or to have hypertension or diabetes, than
      non-Hispanic white patients. ACS/MI disparities also exist among Asian
      populations, and these are briefly outlined. However, black, Hispanic, and non
      Hispanic white ACS/MI patients were the 3 most-studied racial and ethnic groups,
      indicating that additional studies of other minority groups, such as Native
      Americans, Asian populations, and black and Hispanic subgroups, are needed for
      their utility in reducing disparities. Despite notable improvement in ACS/MI
      treatment quality measures over recent decades, disparities persist. Causes are
      complex and extend beyond the healthcare system to culture and patients' personal
      characteristics; sophisticated solutions will be required. Continued research has
      the potential to further reduce or eliminate disparities in the comorbidities,
      delays, and treatments surrounding ACS and MI, extending healthy lifespans of
      many underserved and minority populations, while reducing healthcare costs. 

PMID- 27028200
TI  - Prevalence and associated features of depression in women with Rett syndrome.
AB  - BACKGROUND: Little is known about depression among women with Rett syndrome (RTT)
      despite recent advances in knowledge about RTT. In this study, we aimed to
      establish the prevalence of depression among women with RTT as identified by a
      screening telephone interview and to explore the clinical factors associated with
      this. METHODS: The study employed the cross-sectional analysis of data from
      telephone interviews with carers of 56 women with RTT, using validated
      questionnaires for assessing mental health problems, challenging behaviour and
      RTT severity. RESULTS: Scores on the mental health assessment reached the
      affective/neurotic threshold in eight cases (14.3%). No significant differences
      were found between those reaching the threshold and those who did not in terms of
      severity of RTT phenotype, health problems or social circumstances. There was a
      significant association between screening identified depression and higher
      lethargy and social withdrawal. CONCLUSIONS: Screening identified depression was
      found among a sizeable minority of women with RTT. Further investigation is
      needed to establish a clinically validated prevalence of depression among this
      group and to identify behavioural features that would lead to prompt psychiatric
      assessment.

PMID- 27028199
TI  - Economic Benefits of Investing in Women's Health: A Systematic Review.
AB  - BACKGROUND: Globally, the status of women's health falls short of its potential.
      In addition to the deleterious ethical and human rights implications of this
      deficit, the negative economic impact may also be consequential, but these
      mechanisms are poorly understood. Building on the literature that highlights
      health as a driver of economic growth and poverty alleviation, we aim to
      systematically investigate the broader economic benefits of investing in women's
      health. METHODS: Using the Preferred Reporting Items for Systematic Reviews and
      Meta-Analysis (PRISMA) guidelines, we systematically reviewed health, gender, and
      economic literature to identify studies that investigate the impact of women's
      health on micro- and macroeconomic outcomes. We developed an extensive search
      algorithm and conducted searches using 10 unique databases spanning the timeframe
      01/01/1970 to 01/04/2013. Articles were included if they reported on economic
      impacts stemming from changes in women's health (table of outcome measures
      included in full review, Table 1). In total, the two lead investigators
      independently screened 20,832 abstracts and extracted 438 records for full text
      review. The final review reflects the inclusion of 124 articles. RESULTS: The
      existing literature indicates that healthier women and their children contribute
      to more productive and better-educated societies. This study documents an
      extensive literature confirming that women's health is tied to long-term
      productivity: the development and economic performance of nations depends, in
      part, upon how each country protects and promotes the health of women. Providing
      opportunities for deliberate family planning; healthy mothers before, during, and
      after childbirth, and the health and productivity of subsequent generations can
      catalyze a cycle of positive societal development. CONCLUSIONS: This review
      highlights the untapped potential of initiatives that aim to address women's
      health. Societies that prioritize women's health will likely have better
      population health overall, and will remain more productive for generations to
      come.

PMID- 27028203
TI  - Abstracts of the 17th Annual NATA Symposium on Patient Blood Management,
      Haemostasis and Thrombosis, April 14-15, 2016, Dublin, Ireland.

PMID- 27028201
TI  - Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.
AB  - Ischemia is one of the main epidemic factors and characteristics of diabetic
      chronic wounds, and exerts a profound effect on wound healing. To explore the
      mechanism of and the cure for diabetic impaired wound healing, we established a
      type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD) feeding regimen
      followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to
      induce Wister rat to develop type 2 diabetes. Metabolic characteristics were
      assessed at the 5th week after the STZ injections to confirm the establishment of
      diabetes mellitus on the rodent model. A bipedicle flap, with length to width
      ratio 1.5, was performed on the back of the rat to make the flap area ischemic.
      Closure of excisional wounds on this bipedicle flap and related physiological and
      pathological changes were studied using histological, immunohistochemical, real
      time PCR and protein immunoblot approaches. Our results demonstrated that a
      combination of HFD feeding and a low dose of STZ is capable of inducing the rats
      to develop type 2 diabetes with noticeable insulin resistance, persistent
      hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol
      and high triglyceride levels. The excision wounds on the ischemic double pedicle
      flap showed deteriorative healing features comparing with non-ischemic diabetic
      wounds, including: delayed healing, exorbitant wound inflammatory response,
      excessive and prolonged ROS production and excessive production of MMPs. Our
      study suggested that HFD feeding combined with STZ injection could induce type 2
      diabetes in rat. Our ischemic diabetic wound model is suitable for the
      investigation of human diabetic related wound repair; especically for diabetic
      chronic wounds.

PMID- 27028202
TI  - The fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)
      chemotherapy regimen is an alternative to anthracycline-based therapy for the
      treatment of acute myeloid leukemia for patients with pre-existing cardiac
      disease.
AB  - We conducted a retrospective study assessing FLAG (fludarabine, cytarabine, and
      granulocyte colony-stimulating factor) as first-line treatment in 56 newly
      diagnosed acute myeloid leukemia patients considered ineligible for anthracycline
      based treatment due to advanced age, significant comorbidities, or pre-existing
      cardiac disease. The median age was 69 (21-80); 46% received FLAG for pre
      existing cardiac disease and others due to age (32%), non-cardiac comorbidities
      (20%), or previous anthracycline exposure (2%). The induction mortality was 16%
      and, among evaluable patients, 48% achieved a complete remission after the first
      induction course with an additional patient achieving a remission after a second
      course for a total complete remission rate of 50%. Four patients proceeded to an
      allogeneic stem cell transplant including two with pre-existing cardiac disease.
      Among non-transplanted patients, the relapse rate (RR) was 47%. When censored at
      time of stem cell transplant, the median relapse-free survival was 14.7 months.
      The median overall survival was 9.3 months with 1- and 2-yr survivals of 44% and
      22%, respectively. There was no difference in clinical outcomes between patients
      treated with FLAG for cardiac reasons vs. other reasons. In conclusion, FLAG is a
      useful alternative to anthracycline-based induction for Acute myeloid leukemia in
      those with significant comorbidities including pre-existing cardiac disease.

PMID- 27028204
TI  - Antimicrobial peptide (Cn-AMP2) from liquid endosperm of Cocos nucifera forms
      amyloid-like fibrillar structure.
AB  - Cn-AMP2 is an antimicrobial peptide derived from liquid endosperm of coconut
      (Cocos nucifera). It consists of 11 amino acid residues and predicted to have
      high propensity for beta-sheet formation that disposes this peptide to be
      amyloidogenic. In the present study, we have examined the amyloidogenic
      propensities of Cn-AMP2 in silico and then tested the predictions under in vitro
      conditions. The in silico study revealed that the peptide possesses high
      amyloidogenic propensity comparable with Abeta. Upon solubilisation and agitation
      in aqueous buffer, Cn-AMP2 forms visible aggregates that display bathochromic
      shift in the Congo red absorbance spectra, strong increase in thioflavin T
      fluorescence and fibrillar morphology under transmission electron microscopy. All
      these properties are typical of an amyloid fibril derived from various
      proteins/peptides including Abeta.

PMID- 27028205
TI  - Ribbon structure stabilized by C10 and C12 turns in alphagamma hybrid peptide.
AB  - The present study describes the synthesis and crystallographic analysis of
      alphagamma hybrid peptides, Boc-Gpn-L-Pro-NHMe (1), Boc-Aib-Gpn-L-Pro-NHMe (2),
      and Boc-L-Pro-Aib-Gpn-L-Pro-NHMe (3). Peptides 1 and 2 adopt expanded 12-membered
      (C12 ) helical turn over gammaalpha segment. Peptide 3 promotes the ribbon
      structure stabilized by type II beta-turn (C10 ) followed by the expanded C12
      helical gammaalpha turn. Both right-handed and left-handed helical conformations
      for Aib residue are observed in peptides 2 and 3, respectively.

PMID- 27028206
TI  - Synthesis, binding affinities and metabolic stability of dimeric dermorphin
      analogs modified with beta3-homo-amino acids.
AB  - In this study, proteinogenic amino acids residues of dimeric dermorphin
      pentapeptides were replaced by the corresponding beta(3)-homo-amino acids. The
      potency and selectivity of hybrid alpha/beta dimeric dermorphin pentapeptides
      were evaluated by competetive receptor binding assay in the rat brain using
      [3H]DAMGO (a MU ligand) and [3H]DELT (a delta ligand). Tha analog containing
      beta(3)-homo-Tyr in place of Tyr (Tyr-D-Ala-Phe-Gly-beta(3)-homo-Tyr-NH-)2 showed
      good MU receptor affinity and selectivity (IC50 = 0.302, IC50 ratio MU/delta =
      68) and enzymatic stability in human plasma.

PMID- 27028207
TI  - Synthesis and conformational analysis of an expanded cyclic ketoxime-hexapeptide.
AB  - In this work the synthesis of a linear hexapeptide with a hydroxylamine
      functionality at the N-terminus and a ketone instead of the carboxylic acid at
      the C-terminus is described. Cyclization by ketoxime formation yields the 19
      membered ring-expanded cyclic hexapeptide cyclo[Goly-Val-Ala-Pro-Leu-Kly] which
      adopts a main conformer with two intramolecular hydrogen bonds. The hydrolytic
      stability of a ketoxime lies between the inert amide and the labile imine. The
      substitution of an amide bond for an iminium bond transforms the irreversible
      macrocyclization into a reversible process, but macrocyclic imines are difficult
      to isolate because they are prone to hydrolysis. The enhanced chemical stability
      of the ketoxime justifies its application in ligation protocols. The detailed NMR
      analysis of a ketoxime linkage presented here identifies its local conformational
      preferences in a constrained peptide environment.

PMID- 27028208
TI  - Dimerization effects on coacervation property of an elastin-derived synthetic
      peptide (FPGVG)5.
AB  - Elastin, a core protein of the elastic fibers, exhibits the coacervation
      (temperature-dependent reversible association/dissociation) under physiological
      conditions. Because of this characteristic, elastin and elastin-derived peptides
      have been considered to be useful as base materials for developing various
      biomedical products, skin substitutes, synthetic vascular grafts, and drug
      delivery systems. Although elastin-derived polypeptide (Val-Pro-Gly-Val-Gly)n
      also has been known to demonstrate coacervation property, a sufficiently high
      (VPGVG)n repetition number (n>40) is required for coacervation. In the present
      study, a series of elastin-derived peptide (Phe-Pro-Gly-Val-Gly)5 dimers
      possessing high coacervation potential were newly developed. These novel dimeric
      peptides exhibited coacervation at significantly lower concentrations and
      temperatures than the commonly used elastin-derived peptide analogs; this result
      suggests that the coacervation ability of the peptides is enhanced by
      dimerization. Circular dichroism (CD) measurements indicate that the dimers
      undergo similar temperature-dependent and reversible conformational changes when
      coacervation occurs. The molecular dynamics calculation results reveal that the
      sheet-turn-sheet motif involving a type II beta-turn-like structure commonly
      observed among the dimers and caused formation of globular conformation of them.
      These synthesized peptide dimers may be useful not only as model peptides for
      structural analysis of elastin and elastin-derived peptides, but also as base
      materials for developing various temperature-sensitive biomedical and industrial
      products.

PMID- 27028209
TI  - Variation in the activities of late stage filaggrin processing enzymes, calpain-1
      and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels,
      corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed
      facial stratum corneum of different ethnicities.
AB  - BACKGROUND: Knowledge of the ethnic differences and effects of photodamage on the
      relative amounts of natural moisturizing factor (NMF) together with filaggrin
      processing enzymes in facial stratum corneum is limited. Our aim was to
      characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the
      levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and
      to relate them to plasmin activities and corneocyte maturation. METHODS: Enzyme
      activities, PCA levels and corneocyte maturation were determined from facial tape
      strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of
      healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects
      living in South Africa. RESULTS: PCA concentration levels were of the order AA >
      BA > C subjects, and the highest activities of BH were present in the AA
      subjects. BH activities were greater on the photoexposed sites for the BA and C
      subjects, but they were only numerically elevated in the AA subjects.
      Photoprotected sites had an increase in C-1 activity in pigmented groups (C and
      BA), whereas in the AA subjects, the opposite was measured. Plasmin activities
      were greater on the cheek compared with the PA site for the AA and C subjects,
      but the activity was low in the BA subjects. In both test sites, the AA, but not
      the BA and C subjects, had smaller, parakeratotic and less mature corneocytes.
      CONCLUSION: Variation in PCA levels has been found for different ethnic groups in
      this study (AA > BA > C subjects). The values in the AA subjects are surprising
      as one might expect that the lack of pigmentation, and thereby increased
      photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was
      observed in the AA subjects indicating that BH is associated with PCA production
      to a greater extent. Surprisingly, corneocyte maturation is still impaired with
      elevated PCA levels in AA subjects. The higher levels of plasmin and BH
      activities on the cheeks, especially for AA and C subjects, suggest that they can
      be used as markers for epidermal photodamage.

PMID- 27028210
TI  - Reduced alloimmunization in mice following repeated transfusion with pathogen
      reduced platelets.
AB  - BACKGROUND: Allogeneic transfusion can result in alloimmunization, leading to
      platelet (PLT) refractoriness and rejection of solid organ transplants.
      Previously we demonstrated that pathogen reduction using UV light and riboflavin
      (UV + R) eliminates the immunogenicity of white blood cells (WBCs) in vitro,
      blocks alloimmunization from transfusion in mice, and results in reduced ex vivo
      cytokine responses to subsequent untreated transfusions. We sought to determine
      if repeated transfusion with pathogen-reduced PLT-rich plasma (PRP) would
      eventually cause breakthrough alloimmunization or enhanced tolerance. STUDY
      DESIGN AND METHODS: BALB/cJ mice were transfused weekly for 2, 4, or 8 weeks with
      C57Bl/6J PRP that was either untreated or pathogen reduced with UV + R and
      leukoreduced or not. Alloimmunization was determined by measuring donor antibody
      levels, ex vivo cytokine responses, and 24-hour donor PLT recovery. The role of
      donor antibodies in PLT refractoriness was also assessed by transfer of diluted
      immune sera into naive recipients. RESULTS: Donor antibody levels increased with
      the number of transfusions, but levels were significantly reduced using either UV
      + R or leukoreduction, and combining UV + R and leukoreduction gave the best
      protection. Priming of ex vivo cytokine responses required WBCs and remained
      suppressed with repeated UV + R-treated transfusion. PLT recovery was reduced
      with UV + R in naive mice, and multiply transfused mice had poor PLT recovery
      even when antibody levels were relatively low. Approximately 1/100 dose of serum
      from a multiply transfused mouse was sufficient for complete rejection of donor
      PLTs. CONCLUSIONS: Pathogen reduction significantly reduces alloimmunization in
      repeatedly transfused mice and combined with leukoreduction provides a high level
      of protection from alloimmunization.

PMID- 27028211
TI  - Clinical presentation, treatment and outcome in 31 dogs with presumed primary
      colorectal lymphoma (2001-2013).
AB  - The objective of this multicentre retrospective study was to describe clinical
      presentation, treatment and outcome and to determine prognostic factors for dogs
      with presumed primary colorectal lymphoma (PCRL). A total of 31 dogs were
      included. The predominant features of PCRL were high grade (n = 18) and
      immunophenotype B (n = 24). Most dogs were substage b (n = 25) with higher
      prevalence of haematochezia (n = 20). One dog had surgery only. Thirty dogs
      received chemotherapy; amongst them 13 had surgery or radiotherapy. Progression
      free survival (PFS) was 1318 days and disease-related median survival time (MST)
      was 1845 days. Fourteen dogs were alive at the end of the study with a median
      follow-up time of 684 days (3-4678 days). Younger dogs had longer PFS (P = 0.031)
      and disease-related MST (P = 0.01). Presence of haematochezia corresponded with
      longer PFS (P = 0.02). Addition of local treatment to chemotherapy did not
      significantly improve the outcome (P = 0.584). Canine PCRL has considerably
      longer PFS and MST than other forms of non-Hodgkin's lymphoma.

PMID- 27028212
TI  - Analysing the mutational status of adenomatous polyposis coli (APC) gene in
      breast cancer.
AB  - BACKGROUND: Breast cancer is a heterogeneous disorder for which the underlying
      genetic basis remains unclear. We developed a method for identifying adenomatous
      polyposis coli (APC) mutations and we evaluated the possible association between
      APC genetic variants and breast cancer susceptibility. METHODS: Genomic DNA was
      extracted from tumor and matched peripheral blood samples collected from 89
      breast cancer patients and from peripheral blood samples collected from 50
      controls. All samples were tested for mutations in exons 1-14 and the mutation
      cluster region of exon 15 by HRM analysis. All mutations were confirmed by direct
      DNA sequencing. RESULTS: We identified a new single nucleotide polymorphism
      (SNP), c.465A>G (K155K), in exon 4 and seven known SNPs: c.573T>C (Y191Y) in exon
      5, c.1005A>G (L335L) in exon 9, c.1458T>C (Y486Y) and c.1488A>T (T496T) in exon
      11, c.1635G>A (A545A) in exon 13, and c.4479G>A (T1493T) and c.5465T>A (V1822D)
      in exon 15. The following alterations were found in 2, 1, 2, and 1 patients,
      respectively: c.465A>G, c.573T>C, c.1005A>G, and c.1488A>T. There was no observed
      association between breast cancer risk and any of these APC SNPs. CONCLUSIONS:
      APC mutations occur at a low frequency in Taiwanese breast cancer cases. HRM
      analysis is a powerful method for the detection of APC mutations in breast.

PMID- 27028213
TI  - Physically Transient Resistive Switching Memory Based on Silk Protein.
AB  - Physically transient resistive switching devices based on silk protein are
      successfully demonstrated. The devices can be absolutely dissolved in deionized
      water or in phosphate-buffered saline in 2 h. At the same time, a reasonable
      resistance OFF/ON ratio of larger than 10(2) and a retention time of more than
      10(4) s are achieved for nonvolatile memory applications. 

PMID- 27028214
TI  - Low positive predictive value of midnight salivary cortisol measurement to detect
      hypercortisolism in type 2 diabetes.
AB  - BACKGROUND: Hypercortisolism is prevalent in type 2 diabetes (T2D), but
      analytical and functional uncertainties prevail. Measurement of salivary cortisol
      is considered an expedient screening method for hypercortisolism, but its
      usefulness in the context of T2D is uncertain. AIM: To compare late-night
      salivary cortisol (LNSC) with the 1 mg overnight dexamethasone suppression test
      (DST), which was considered 'reference standard', in T2D. PATIENTS AND METHODS: A
      total of 382 unselected and recently diagnosed patients with T2D underwent
      assessment of LNSC and DST, and the test outcome was related to age, gender, body
      mass index (BMI) and haemoglobin A1c levels. We used the following cut-off
      values: LNSC <= 3.6 nmol/l and DST <= 50 nmol/l. RESULTS: The median (range)
      levels of LNSC and DST were 6.1 (0.3-46.2) nmol/l and 34 (11-547) nmol/l,
      respectively. Hypercortisolism was present in 86% based on LNSC values and 22%
      based on DST. LNSC, as compared to DST, had the following test characteristics:
      sensitivity: 85% (95% CI: 7-92%), specificity: 14% (95% CI: 10-19%), positive
      predictive value: 22% (95% CI: 17-27%), negative predictive value: 76% (95% CI:
      63-87%), and overall accuracy: 30% (95% CI: 25-34%). LNSC and DST values were not
      associated with haemoglobin A1c, BMI and age in this cohort of patients with T2D.
      CONCLUSION: The LNSC is characterized by very low specificity and poor positive
      predictive value as compared to the DST, resulting in an overall low accuracy.
      Further methodological and clinical studies are needed to substantiate the
      relevance of cortisol status in T2D.

PMID- 27028215
TI  - Cytochrome c-Capped Fluorescent Gold Nanoclusters: Imaging of Live Cells and
      Delivery of Cytochrome c.
AB  - Cytochrome c-capped fluorescent gold nanoclusters (Au-NCs) are used for imaging
      of live lung and breast cells. Delivery of cytochrome c inside the cells is
      confirmed by covalently attaching a fluorophore (Alexa Fluor 594) to cytochrome c
      capped Au-NCs and observing fluorescence from Alexa 594 inside the cell. Mass
      spectrometry studies suggest that in bulk water, addition of glutathione (GSH) to
      cytochrome c-capped Au-NCs results in the formation of glutathione-capped Au-NCs
      and free apo-cytochrome c. Thus glutathione displaces cytochrome c as a capping
      agent. Using confocal microscopy, the emission spectra and decay of Au-NCs are
      measured in live cells. From the position of the emission maximum it is shown
      that the Au-NCs exist as Au8 in bulk water and as Au13 inside the cells.
      Fluorescence resonance energy transfer from cytochrome c-Au-NC (donor) to
      Mitotracker Orange (acceptor) indicates that the Au-NCs localise in the
      mitochondria of live cells.

PMID- 27028216
TI  - Catalytic Diazosulfonylation of Enynals toward Diazoindenes via Oxidative Radical
      Triggered 5-exo-trig Carbocyclizations.
AB  - Catalytic diazosulfonylation of enynals with arylsulfonyl hydrazides has been
      established by using tert-butyl hydroperoxide (TBHP) as the oxidant with
      tetrabutylammonium iodide (TBAI) under a convenient system. The reaction occurred
      through oxidative radical-triggered 5-exo-trig carbocyclization cascading to
      afford sulfonylated diazoindenes regioselectively. The new diazosulfonylation
      reaction features a broad substrate scope, readily accessible starting materials,
      and a simple one-pot process. 

PMID- 27028217
TI  - Nuclear protein in testis midline carcinoma of larynx: An underdiagnosed entity.
AB  - BACKGROUND: Nuclear protein in testis (NUT) carcinomas are very rare and have a
      very poor survival rate. The most common sites of involvement include the nasal
      cavity, sinus, and mediastinum. Laryngeal NUT midline carcinoma is extremely
      rare, with only 2 cases reported thus far. Here, we are describing another case
      of NUT laryngeal carcinoma. METHODS AND RESULTS: The patient was a light smoker
      and nondrinker who presented with upper respiratory tract obstruction. Imaging
      and laryngoscopic evaluation revealed a large intraluminal laryngeal mass. Biopsy
      demonstrated poorly differentiated carcinoma with intact mucosa and only focal
      coexpression of CK5/6 and p40. NUT protein immune-stain positivity conclusively
      established the diagnosis of NUT midline carcinoma. CONCLUSION: Absence of well
      known risk factors, pathologic finding of lack of mucosal involvement and lack of
      squamous differentiation with poorly differentiated carcinoma, should prompt
      clinicians to consider this rare entity as a possible diagnosis. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 38:E2471-E2474, 2016.

PMID- 27028219
TI  - Futile Education: When Graduation Is Not the Best Option.

PMID- 27028218
TI  - Mediator and TREX-2: Emerging links between transcription initiation and mRNA
      export.
AB  - Nuclear pore proteins interact dynamically with chromatin to regulate gene
      activities. A key question is how nucleoporin interactions mechanistically alter
      a gene's intranuclear position and transcriptional output. We reported recently
      on a direct interaction between the nuclear pore-associated TREX-2 complex and
      promoter-bound Mediator. This highlights how nuclear-pore associated adaptors
      gain regulatory access to the core transcription machinery. In this Extra View,
      we discuss an additional implication that arises from our work and the recent
      literature: how promoter elements may regulate mRNA metabolism beyond
      transcription initiation.

PMID- 27028220
TI  - Big Data from Pharmaceutical Patents: A Computational Analysis of Medicinal
      Chemists' Bread and Butter.
AB  - Multiple recent studies have focused on unraveling the content of the medicinal
      chemist's toolbox. Here, we present an investigation of chemical reactions and
      molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used
      a sophisticated text-mining pipeline to extract 1.15 million unique whole
      reaction schemes, including reaction roles and yields, from pharmaceutical
      patents. The reactions were assigned to well-known reaction types such as Wittig
      olefination or Buchwald-Hartwig amination using an expert system. Analyzing the
      evolution of reaction types over time, we observe the previously reported bias
      toward reaction classes like amide bond formations or Suzuki couplings. Our study
      also shows a steady increase in the number of different reaction types used in
      pharmaceutical patents but a trend toward lower median yield for some of the
      reaction classes. Finally, we found that today's typical product molecule is
      larger, more hydrophobic, and more rigid than 40 years ago.

PMID- 27028221
TI  - Relationship between androgenetic alopecia and cardiovascular risk factors
      according to BASP classification in Koreans.
AB  - There have been many studies on the relationship between androgenetic alopecia
      (AGA) and cardiovascular risk factors, but the study results were inconsistent
      and research on AGA in Asians remains insufficient. This study investigated the
      relationship between Korean AGA and various cardiovascular risk factors,
      considering life habits, type of hair loss and sex. We investigated subjects who
      visited a hospital for public or industrial health medical examinations between
      October 2012 and December 2014. A questionnaire as well as anthropometric
      measurements and a blood test were performed. Among the 1884 total subjects,
      52.6% had AGA. AGA patients displayed a significantly higher prevalence rate of
      cardiovascular diseases, smoking rate, fasting glucose and triglyceride, and a
      significantly lower high-density lipoprotein cholesterol level than did the non
      AGA group. The results of the subgroup analysis showed higher prevalence rates of
      hypertension, stroke, metabolic syndrome and smoking in male AGA patients. The
      more severe the AGA, the higher the incidences of hypertension, diabetes and
      smoking were observed. According to the analysis results by BASP classification,
      the F-type AGA patients displayed a higher body mass index, waist circumference
      and diastolic blood pressure, and had a significantly higher prevalence rate of
      hypertension. As a result of the large population-based study, modifications in
      lifestyle and early screening for cardiovascular disease, as well as hypertension
      and diabetes, are suggested.

PMID- 27028222
TI  - Chemical anatomy of pallidal afferents in primates.
AB  - Neurons of the globus pallidus receive massive inputs from the striatum and the
      subthalamic nucleus, but their activity, as well as those of their striatal and
      subthalamic inputs, are modulated by brainstem afferents. These include serotonin
      (5-HT) projections from the dorsal raphe nucleus, cholinergic (ACh) inputs from
      the pedunculopontine tegmental nucleus, and dopamine (DA) afferents from the
      substantia nigra pars compacta. This review summarizes our recent findings on the
      distribution, quantitative and ultrastructural aspects of pallidal 5-HT, ACh and
      DA innervations. These results have led to the elaboration of a new model of the
      pallidal neuron based on a precise knowledge of the hierarchy and chemical
      features of the various synaptic inputs. The dense 5-HT, ACh and DA innervations
      disclosed in the associative and limbic pallidal territories suggest that these
      brainstem inputs contribute principally to the planification of motor behaviors
      and the regulation of attention and mood. Although 5-HT, ACh and DA inputs were
      found to modulate pallidal neurons and their afferents mainly through asynaptic
      (volume) transmission, genuine synaptic contacts occur between these
      chemospecific axon varicosities and pallidal dendrites, revealing that these
      brainstem projections have a direct access to pallidal neurons, in addition to
      their indirect input through the striatum and subthalamic nucleus. Altogether,
      these findings reveal that the brainstem 5-HT, ACh and DA pallidal afferents act
      in concert with the more robust GABAergic inhibitory striatopallidal and
      glutamatergic excitatory subthalamopallidal inputs. We hypothesize that a fragile
      equilibrium between forebrain and brainstem pallidal afferents plays a key role
      in the functional organization of the primate basal ganglia, in both health and
      disease.

PMID- 27028226
TI  - Multiple sigmaEcfG and NepR Proteins Are Involved in the General Stress Response
      in Methylobacterium extorquens.
AB  - In Alphaproteobacteria, the general stress response (GSR) is controlled by a
      conserved partner switch composed of the sigma factor sigma(EcfG), its anti-sigma
      factor NepR and the anti-sigma factor antagonist PhyR. Many species possess
      paralogues of one or several components of the system, but their roles remain
      largely elusive. Among Alphaproteobacteria that have been genome-sequenced so
      far, the genus Methylobacterium possesses the largest number of sigma(EcfG)
      proteins. Here, we analyzed the six sigma(EcfG) paralogues of Methylobacterium
      extorquens AM1. We show that these sigma factors are not truly redundant, but
      instead exhibit major and minor contributions to stress resistance and GSR target
      gene expression. We identify distinct levels of regulation for the different
      sigma factors, as well as two NepR paralogues that interact with PhyR. Our
      results suggest that in M. extorquens AM1, ecfG and nepR paralogues have diverged
      in order to assume new roles that might allow integration of positive and
      negative feedback loops in the regulatory system. Comparison of the core elements
      of the GSR regulatory network in Methylobacterium species provides evidence for
      high plasticity and rapid evolution of the GSR core network in this genus.

PMID- 27028227
TI  - Squamocellular Carcinoma of the Skin: Clinicopathological Features Predicting the
      Involvement of the Surgical Margins and Review of the Literature.
AB  - BACKGROUND: The new AJCC classification has highlighted some particular risk
      factors for squamous cell carcinoma (SCC) relevant for prognosis. Incomplete
      excision is not infrequent in SCC. The aim of this study is to examine features
      that can predict an incomplete excision on the basis of the new AJCC
      classification and to review the literature on this topic. MATERIALS AND METHODS:
      81 SCC patients were included. All patients were submitted to excisional biopsy
      with a margin of at least 4 mm from the clinical edges as recommended.
      Histological characteristics of the lesions analysed were maximum diameter,
      grading, site, Breslow thickness, Clark level, deep tissue invasion (neural,
      bone, muscle), presence of ulceration and positivity of the margins. RESULTS: The
      average Breslow thickness was 3.93 mm. Out of the 81 patients included, 14 showed
      involved margins. The 2 parameters that were implicated in predicting involvement
      of the margins in the multivariable model were Breslow thickness and location of
      the lesion on the ear or lip. Grading was not associated with involvement of
      margins. CONCLUSION: According to the new AJCC classification, this study could
      be useful to plan the most suitable surgical technique in order to avoid the risk
      of incomplete surgery.

PMID- 27028228
TI  - Helicobacter pylori and Other Gastric Microbiota in Gastroduodenal Pathologies.
AB  - The discovery of Helicobacter pylori changed the traditional view of the stomach
      as a hostile organ to bacterial survival. H. pylori induces chronic gastritis,
      which has the potential to progress to severe complications such as peptic ulcer
      disease and gastric neoplasia. The development of modern nucleotide sequencing
      techniques and new biocomputational tools allow the possibility of studying the
      diversity and complexity of the microbiome in the whole gastrointestinal (GI)
      tract and overcome the limitations of culturing techniques. However, the
      differentiation of alive resident and transient microbes in the upper GI tract
      and their role in the pathogenesis of gastroduodenal diseases requires an
      analysis beyond the detection of bacterial genomic material alone. Metabolomic
      and transcriptomic analyses of the bacteria may add important insights into their
      interaction with the host. Currently, the interaction of H. pylori with other
      microbes in the stomach and duodenum and their role for health and disease is
      poorly understood. This review provides a concise overview on the current
      knowledge of H. pylori and other gastric microbiota in the relationship with
      gastroduodenal pathologies. 

PMID- 27028230
TI  - [Is instillation of bone marrow stem cells at the time of core decompression
      useful for osteonecrosis of the femoral head?].
AB  - Osteonecrosis of the femoral head leads to degeneration of the head and finally
      to osteoarthritis of the hip. Decompression is the most widely used treatment,
      but its effectiveness is limited. It has been proposed instillation of stem cells
      in addition to decompression, would lead to better results. Searching in
      Epistemonikos database, which is maintained by screening 30 databases, we
      identified two systematic reviews including two randomized trials. We combined
      the evidence using meta-analysis and generated a summary of findings table
      following the GRADE approach. We concluded instillation of bone marrow stem cells
      at the time of core decompression probably slows progression to osteoarthritis of
      the hip in patients with osteonecrosis of the femoral head and might reduce the
      need of subsequent surgeries. It is unclear whether it has any effect on the
      functionality because the certainty of the evidence is very low. 

PMID- 27028229
TI  - Individual and community factors for railway suicide: a matched case-control
      study in Victoria, Australia.
AB  - PURPOSE: This study aims to simultaneously examine individual- and community
      level factors associated with railway suicide. METHODS: We performed a case
      control study in Victoria, Australia between 2001 and 2012. Data on cases of
      railway suicide were obtained from the National Coronial Information System (a
      database of coronial investigations). Controls were living individuals randomly
      selected from the Household, Income and Labour Dynamics in Australia study,
      matching to cases on age groups, sex and year of exposures. A conditional
      logistic regression model was used to assess the individual-level and community
      level influences on individual odds of railway suicide, controlling for
      socioeconomic status. RESULTS: Individual-level diagnosed mental illness
      increased railway suicide odds by six times [95 % confidence interval (CI) 4.5,
      9.2]. Community-level factors such as living in an area with a presence of
      railway tracks [odds ratio (OR) 1.8, 95 % CI 1.2, 2.8], within a city (OR 3.2, 95
      % CI 1.9, 5.4), and with a higher overall suicide rate (OR 1.02, 95 % CI 1.01,
      1.04) were independently associated with greater individual odds of railway
      suicide compared to living in an area without a presence of railway tracks,
      outside a city, and with a relatively lower overall suicide rate. CONCLUSIONS:
      The effects of mental illness and high incidence of overall suicides are
      prominent, but not specific on railway suicide. The effects of presence of
      railway tracks and city residence suggest the importance of accessibility to the
      railways for individual risk of railway suicide. Prevention efforts should focus
      on vulnerable people live in areas with easy access to the railways.

PMID- 27028231
TI  - The Motor Cortex Modulates the "When" of Tic Generation in the Rat Striatal
      Disinhibition Model.

PMID- 27028232
TI  - First-trimester maternal abdominal adiposity and adiponectin in pregnancy.

PMID- 27028233
TI  - Interobserver reliability of ultrasound assessment of haemophilic arthropathy:
      radiologist vs. non-radiologist.

PMID- 27028234
TI  - Evaluation of a National Broadband Network-enabled Telehealth trial for older
      people with chronic disease.
AB  - Objective The aim of the present study was to evaluate the effect of a high-speed
      telemonitoring project for older people with chronic disease in a regional
      Australian town. Participants' vital signs were monitored and triaged daily by a
      telehealth nurse. Methods A prospective, uncontrolled study design evaluated the
      effect of home-based telemonitoring on older people with chronic disease.
      Evaluation included surveys (including the Stanford Chronic Disease Self-Efficacy
      tool and the Self-Rated Health Questionnaire), self-reported health service use
      and interviews and focus groups exploring client experiences. Results
      Participants reported an improved understanding of their vital signs monitoring
      (48%) and consequently better self-management of health (48%) and that they were
      better informed (44%) and more confident (25%) to discuss health with their
      doctor. Patients also reported making medication changes (17%), positive dietary
      changes (34%) and increasing their physical activity (33%). Overall, patients'
      self-rated general health improved (mean (+/- s.d.) improvement 0.30+/-0.80; 95%
      confidence interval (CI) 0.16-0.45; 118 d.f.; P<0.001), with more participants
      reporting that their health is 'excellent' or 'very good' at the end of the
      trial. Patients also reported fewer doctor visits (P<0.001), fewer visits to the
      local hospital emergency department (P=0.021) and fewer non-local hospital
      admissions (P<0.001) compared with the preceding year. There was no significant
      reduction in local hospital admissions (P=0.171). Conclusions The findings of the
      present study suggest that telemonitoring with videoconferencing empowers older
      people to better understand and manage their own health, and is associated with
      improved health outcomes and reduced service use. Having regular, daily access to
      a Telehealth nurse reassured participants, and triggered changes to services and
      behaviour that are likely to have positively affected patient outcomes. What is
      known about this topic? Telehealth is increasingly being used in the care of
      older people with chronic conditions and can reduce health service use. Previous
      research has indicated that telehealth has the potential to provide patients with
      greater knowledge and understanding of their condition. What this paper adds? Our
      research demonstrates that older people with limited experience of technology can
      be taught to successfully use telehealth equipment. We observed regular contact
      with telehealth nurses enables health promoting behaviour messages to be tailored
      to patients' needs. What are the implications for practitioners? Providing older
      people with tailored health support alongside an understanding of vital signs
      readings can enhance self-efficacy.

PMID- 27028235
TI  - Probing RNA Native Conformational Ensembles with Structural Constraints.
AB  - Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of
      cellular processes, ranging from regulating gene expression to post-translational
      modification and protein synthesis. Their activity is modulated by highly dynamic
      exchanges between three-dimensional conformational substates, which are difficult
      to characterize experimentally and computationally. Here, we present an
      innovative, entirely kinematic computational procedure to efficiently explore the
      native ensemble of RNA molecules. Our procedure projects degrees of freedom onto
      a subspace of conformation space defined by distance constraints in the tertiary
      structure. The dimensionality reduction enables efficient exploration of
      conformational space. We show that the conformational distributions obtained with
      our method broadly sample the conformational landscape observed in NMR
      experiments. Compared to normal mode analysis-based exploration, our procedure
      diffuses faster through the experimental ensemble while also accessing
      conformational substates to greater precision. Our results suggest that
      conformational sampling with a highly reduced but fully atomistic representation
      of noncoding RNA expresses key features of their dynamic nature.

PMID- 27028236
TI  - Obese adolescents with type 2 diabetes perform worse than controls on cognitive
      and behavioral assessments.
AB  - BACKGROUND: Children with type 1 diabetes demonstrate worse cognitive performance
      compared with their peers. Little is known regarding the cognitive and behavioral
      performance in obese adolescents with type 2 diabetes. METHODS: Cross sectional
      evaluation of 20 obese adolescents with type 2 diabetes and 20 healthy
      adolescents was performed in Cincinnati, Ohio. Cognitive tests that included
      measures of processing speed, working memory, verbal and semantic fluency and
      parent reports of executive function and problem behavior were compared. Academic
      achievement and the relationship between cognitive/behavioral scores and diabetes
      duration and diabetes control (hemoglobin A1c) were assessed in the type 2
      diabetes group only. RESULTS: The type 2 diabetes group had mean duration of
      diabetes of 2.8 +/- 2.2 yr and hemoglobin A1c of 7.9 +/- 2.2%. Adolescents with
      type 2 diabetes scored lower than controls on tests of working and verbal memory
      and processing speed (all p < 0.05) and worse for Internalizing, Externalizing,
      and Total Problems behaviors on the Child Behavior Checklist (all p < 0.05).
      Adolescents with type 2 diabetes scored below the population mean in academic
      achievement, most notably calculation. Working memory and processing speed were
      negatively correlated with duration of diabetes (r = -0.50 and -0.47,
      respectively, p < 0.05). CONCLUSIONS: Obese youth with type 2 diabetes score
      poorly compared with controls on multiple assessments of cognitive function and
      adaptive behavior. Further work is needed to determine if these effects are
      driven by obesity, diabetes or other demographic and socioeconomic risk factors.

PMID- 27028237
TI  - Reply to Noone et al.

PMID- 27028238
TI  - Electron-Vibron Coupling at Metal-Organic Interfaces from Theory and Experiment.
AB  - We study the significance and characteristics of interfacial dynamical charge
      transfer at metal-organic interfaces for the organic semiconductor model system
      1,4,5,8-naphthalene-tetra-carboxylic dianhydride (NTCDA) on Ag(111)
      quantitatively. We combine infrared absorption spectroscopy and dispersion
      corrected density functional theory calculations to analyze dynamic dipole
      moments and electron-vibron coupling at the interface. We demonstrate that
      interfacial dynamical charge transfer is the dominant cause of infrared activity
      in these systems and that it correlates with results from partial charge and
      density of states analysis. Nuclear motion generates an additional dynamic dipole
      moment but represents a minor effect except for modes with significant out-of
      plane amplitudes. 

PMID- 27028239
TI  - Effect of Hydrochloric Acid Decalcification on Expression Pattern of Prognostic
      Markers in Invasive Breast Carcinomas.
AB  - CONTEXT: In the United States, it is estimated that 100,000 people are living
      with metastatic breast cancer (BC) with bone representing the most common site of
      involvement. However, patients with isolated bone metastasis at presentation may
      have a longer survival. Therapeutic options for BC bone metastases often include
      systemic anticancer therapy (endocrine, chemotherapy, monoclonal antibodies,
      and/or other targeted therapies), which is largely dependent on the
      immunohistochemical (IHC) repertoire of the cancer for the prognostic markers
      [estrogen (ER) and progesterone receptors (PR), Ki-67, p53, and Her-2/neu] at its
      osseous metastatic site. Traditionally, specimens obtained from the bone
      metastasis require decalcification, which may affect the immunoreactivity of
      these prognostic markers. To the best of our knowledge, limited studies describe
      the effect of decalcification on immunoexpression of the above-mentioned markers.
      A detailed illustration of the effect of decalcification on BC specimens in a
      real-time manner is lacking in the literature. OBJECTIVE: Herein, we sought to
      determine the impact of decalcification on the IHC expression pattern of the
      above listed markers on BC tissue following decalcification. DESIGN: After
      Institutional Review Board approval, sections from the residual tumor specimens
      were collected prospectively from 15 BC excision specimens and 1 curetting from a
      BC bone metastasis. The sections (3 to 6 sections/case) for decalcification were
      collected following routine submission for pathologic evaluation. The sections
      were subjected to hydrochloric acid (HCl)-based Decal Stat decalcifying solution
      for 2, 12, 18, and 24 hours in each case. IHC studies for ER, PR, Ki-67, p53, and
      Her-2/neu were performed on 1 representative section of the regularly processed
      tumor block and 1 decalcified tumor block from each time point. Scoring of ER and
      PR were performed according to the Allred scoring system. Scoring of Her-2/neu
      was performed according to CAP/ASCO guidelines. RESULTS: The tumors comprised 11
      grade 3 invasive ductal carcinomas, 2 grade 2 invasive ductal carcinomas, 2 grade
      3 invasive lobular carcinoma, and 1 metastatic BC to bone. Nine cases showed
      Allred score 8 for ER, 1 case showed Allred score 4, 1 case showed Allred score
      2, and the remaining 5 were ER negative. For PR, 1 showed Allred score 8, 2
      Allred score 7, 4 Allred score 6, 1 each Allred score 5 and score 2 with the
      remainder negative for PR. Ki-67 ranged from 5% to 95%. Five cases showed p53
      overexpression ranging from 35% to 95%. Five cases each showed 3+, 6 cases showed
      2+ Her-2/neu, 3 cases showed 1+ Her-2/neu, and the remaining 2 were negative. All
      specimens demonstrated decline in ER, PR, Ki-67, and p53 immunoreactivity after 2
      hours of decalcification, with additional decline up to 24 hours. The most
      significant declines in immunoreactivity occurred with Ki-67 and p53. Most of the
      Her-2/neu cases with an equivocal score declined to zero after 24 hours of
      decalcification. However, 3 out of 11 cases showing Her-2/neu overexpression
      remained at the baseline scoring even after extended (24 h) decalcification.
      CONCLUSIONS: Our results demonstrated that the decalcification process affects
      the immunoreactivity of the prognostic BC markers. There is progressive loss of
      reactivity at 2 hours and beyond for markers with lower degrees of expression. In
      addition, heterogeneity in marker distribution progressed from diffuse to more
      focal beyond 1 hour.

PMID- 27028241
TI  - Renal Splenosis: Renal Mass Biopsy Diagnosis of a Tumor Clinically Mimicking
      Renal Cell Carcinoma.
AB  - Renal mass biopsy is increasingly used to guide conservative tumor management,
      placing increasing importance on pathologists' ability to diagnose small tumor
      samples. A 66-year-old man with a history of prior splenectomy for trauma
      presented for urologic evaluation after identification of a left 5.8 cm renal
      mass. Partial envelopment of the mass by renal parenchyma and equivocal
      enhancement on computed tomography raised concern for renal cell carcinoma.
      Needle-core biopsy revealed blood, subtle vasculature, few aggregates of
      lymphocytes, and rare renal tubules. Immunohistochemical staining revealed CD8
      positive sinusoids but negative reactivity for epithelial antigens (PAX8,
      keratin, epithelial membrane antigen, carbonic anhydrase IX), supporting
      diagnosis of renal splenosis. Renal splenosis is a rare phenomenon that can form
      a sizeable intrarenal mass, mimicking renal cell carcinoma. Pathologists'
      awareness of this uncommon occurrence may avoid unnecessary surgery. CD8-positive
      sinusoids and negative epithelial markers are helpful confirmatory features in
      the biopsy setting.

PMID- 27028240
TI  - Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic
      Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation
      Sequencing.
AB  - Targeted therapy combined with companion diagnostics has led to the advancement
      of next-generation sequencing (NGS) for detection of molecular alterations.
      However, using a diagnostic test to identify patient populations with low
      prevalence molecular alterations, such as gene rearrangements, poses efficiency,
      and cost challenges. To address this, we have developed a 2-step diagnostic test
      to identify NTRK1, NTRK2, NTRK3, ROS1, and ALK rearrangements in formalin-fixed
      paraffin-embedded clinical specimens. This test is comprised of
      immunohistochemistry screening using a pan-receptor tyrosine kinase cocktail of
      antibodies to identify samples expressing TrkA (encoded by NTRK1), TrkB (encoded
      by NTRK2), TrkC (encoded by NTRK3), ROS1, and ALK followed by an RNA-based
      anchored multiplex polymerase chain reaction NGS assay. We demonstrate that the
      NGS assay is accurate and reproducible in identification of gene rearrangements.
      Furthermore, implementation of an RNA quality control metric to assess the
      presence of amplifiable nucleic acid input material enables a measure of
      confidence when an NGS result is negative for gene rearrangements. Finally, we
      demonstrate that performing a pan-receptor tyrosine kinase immunohistochemistry
      staining enriches detection of the patient population for gene rearrangements
      from 4% to 9% and has a 100% negative predictive value. Together, this 2-step
      assay is an efficient method for detection of gene rearrangements in both
      clinical testing and studies of archival formalin-fixed paraffin-embedded
      specimens.

PMID- 27028242
TI  - The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From
      Nonmalignant Lesions.
AB  - BACKGROUND AND AIM: Distinction of small-sized hepatocellular carcinoma (HCC)
      from dysplastic nodules may be difficult. In addition, distinction of well
      differentiated HCC (WD-HCC) from high-grade dysplastic nodule (HGDN) is also
      difficult in small needle biopsy. We aimed to study serine peptidase inhibitor,
      Kazal type 1 (SPINK1) immunohistochemical expression in HCC to differentiate it
      from nonmalignant lesions. METHODS: This study included 179 specimens from the
      archival material of Pathology Department, National Liver Institute, Menoufia
      University, between 2007 and 2014, divided as 93 HCC and 86 nonmalignant lesions.
      All cases were stained for SPINK1 antibody. RESULTS: SPINK1 was expressed in
      76.3% of HCC cases with a diagnostic accuracy of 79.3%.There was a significant
      difference between focal nodular hyperplasia and WD-HCC cases regarding mean
      value of SPINK1 expression (P=0.015). In addition, there was low SPINK1 score in
      cirrhosis cases compared with WD-HCC. Moreover, there was a high significant
      difference between WD-HCC and HGDN regarding SPINK1 expression (P=0.001), with
      83.3% sensitivity and 84.6% specificity. CONCLUSIONS: SPINK1 can be used to
      differentiate between a WD-HCC and a HGDN with high diagnostic validity.

PMID- 27028243
TI  - Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry
      in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas.
AB  - Distinguishing dedifferentiated liposarcoma (DDLPS) from other high-grade spindle
      and pleomorphic sarcomas is important because of better prognosis in case of
      DDLPS. MDM2 amplification, a genetic abnormality of well-differentiated
      liposarcoma, is known to be present not only in DDLPS, but also in some other
      sarcomas. To differentiate DDLPS, we investigated MDM2 amplification and
      expression in high-grade spindle sarcomas. Eighty-five cases of nonlipogenic high
      grade sarcomas, diagnosed between 2008 and 2011, were investigated. Tissue
      microarray, immunohistochemistry, and fluorescence in situ hybridization for MDM2
      were performed. Forty-one of 85 cases (48.2%) showed MDM2 amplification and
      expression. Cases of MDM2 amplification were reclassified based on histology,
      immunophenotype, and clinical data. Thirty-nine of 41 cases, including those
      originally diagnosed as DDLPS (n=30), undifferentiated pleomorphic sarcoma (n=7),
      myxofibrosarcoma (n=1), and pleomorphic liposarcoma (n=1) could be reclassified
      as DDLPS. In addition, MDM2 immunohistochemistry and MDM2 fluorescence in situ
      hybridization showed an excellent correlation (P<0.001, sensitivity 92.7%,
      specificity 100%). MDM2 amplification and expression are potentially very useful
      in distinguishing between DDLPS and other undifferentiated high-grade spindle and
      pleomorphic sarcomas, even though a few other sarcomas also showed MDM2
      amplification and expression.

PMID- 27028244
TI  - Interleukin 18 -607 A/C Gene Polymorphism is Associated With Susceptibility to
      IgA Nephropathy in a Chinese Han Population.
AB  - The association between a single-nucleotide polymorphism (SNP; -607A/C) in the
      promoter region of the IL-18 gene with IL-18 promoter transcription activity and
      the level of IL-18 protein production has been observed repeatedly. However, the
      association between the IL-18-607A/C (rs1946518) promoter polymorphism and IgA
      nephropathy (IgAN) in a Chinese Han population is still unclear. A total of 166
      patients with renal biopsy-proven IgAN and 198 healthy controls were recruited
      for this study. The SNP was genotyped by the polymerase chain reaction and the
      high-resolution melting method. Clinical characteristics and pathology grading of
      patients with IgAN were recorded at the time of the kidney biopsy. There was a
      significant difference in the distribution between the AA genotype and the AC/CC
      genotype [P=0.007, OR (95% CI)=1.885 (1.183-3.003)]. However, no significant
      differences were observed between the rs1946518 SNP and quantitative traits (all
      P>0.05) or different pathology grades (Lee's grading system and tubular
      atrophy/interstitial fibrosis according to the Oxford classification) (P=0.769
      and P=0.7) of the patients. We first demonstrated that the AA genotype of the IL
      18-607A/C was associated with an increased susceptibility to IgAN in this
      population.

PMID- 27028245
TI  - Validity of a single lactate measure to predict fixed lactate thresholds in
      athletes.
AB  - This study aimed to validate the use of a single blood lactate concentration
      measure taken following a 12 km h-1 running stage (BLC12) to predict and monitor
      fixed blood lactate concentration (FBLC) thresholds. Three complementary studies
      were undertaken. Study I: the relationships between BLC12 and the running speeds
      at FBLC of 3 mmol L-1 (S3mM) and 4 mmol L-1 (S4mM) measured during a multistage
      running field test were examined in 136 elite athletes. Study II: data from 30
      athletes tested one year apart were used to test the predictive capacity of the
      equations obtained in Study I. Study III: 80 athletes were tested before and
      after an intensified training period to examine whether training-induced changes
      in FBLC thresholds could be predicted and monitored by BLC12. Study I: BLC12 was
      significantly (P < 0.001) and inversely related to S3mM (R2 = 0.89) and S4mM (R2
      = 0.95). Study II: prediction models yielded robust correlations between the
      estimated and measured FBLC thresholds (r = 0.94-0.99; P < 0.001). Study III:
      estimated changes predicted actual training-induced changes in FBLC thresholds (r
      = 0.81-0.91; P < 0.001). This study gives empirical support to use a single
      lactate measure during a sub-maximal running field test as a simple, low-cost and
      practical alternative to FBLC thresholds in athletes.

PMID- 27028246
TI  - Genome-wide gene expression and DNA methylation differences in abnormally cloned
      and normally natural mating piglets.
AB  - Many studies have proved that DNA methylation can regulate gene expression and
      further affect skeletal muscle growth and development of pig, whereas the
      mechanisms of how DNA methylation or gene expression alteration ultimately lead
      to phenotypical differences between the cloned and natural mating pigs remain
      elusive. This study aimed to investigate genome-wide gene expression and DNA
      methylation differences between abnormally cloned and normally natural mating
      piglets and identify molecular markers related to skeletal muscle growth and
      development in pig. The DNA methylation and genome-wide gene expression in the
      two groups of piglets were analysed through methylated DNA immunoprecipitation
      binding high-throughput sequencing and RNA sequencing respectively. We detected
      1493 differentially expressed genes between the two groups, of which 382 genes
      were also differentially methylated. The results of the integrative analysis
      between DNA methylation and gene expression revealed that the DNA methylation
      levels showed a significantly negative and monotonic correlation with gene
      expression levels around the transcription start site of genes. By contrast, no
      notable monotonic correlation was observed in other regions. Furthermore, we
      identified some interesting genes and signalling pathways (e.g. myosin, heavy
      chain 7 and mammalian target of rapamycin) which possibly play essential roles in
      skeletal muscle growth and development. The results of this study provide
      insights into the relationship of DNA methylation with gene expression in newborn
      piglets and into the mechanisms in abnormally cloned animals through somatic cell
      nuclear transfer. 

PMID- 27028247
TI  - A TAXONOMIC STUDY OF THE GENUS PADINA (DICTYOTALES, PHAEOPHYCEAE) INCLUDING THE
      DESCRIPTIONS OF FOUR NEW SPECIES FROM JAPAN, HAWAII, AND THE ANDAMAN SEA(1).
AB  - A taxonomic study of the genus Padina from Japan, Southeast Asia, and Hawaii
      based on morphology and gene sequence data (rbcL and cox3) resulted in the
      recognition of four new species, that is, Padina macrophylla and Padina
      ishigakiensis from Ryukyu Islands, Japan; Padina maroensis from Hawaii; and
      Padina usoehtunii from Myanmar and Thailand. All species are bistratose and
      morphologically different from one another as well as from any known taxa by a
      combination of characters relating to degree of calcification; the structure,
      position, and arrangement of hairlines (HLs) and reproductive sori; and the
      presence or absence of rhizoid-like groups of hairs and an indusium. Molecular
      phylogenetic analyses demonstrated a close relationship between P. ishigakiensis,
      P. macrophylla, P. maroensis, and Padina australis Hauck. The position of P.
      usoehtunii, however, was not fully resolved, being either sister to a clade
      comprising the other three new species and P. australis in the rbcL tree or more
      closely related to a clade comprising several other recently described species in
      the cox3 tree. The finding of the four new species demonstrates high species
      diversity particularly in southern Japan. The following characters were first
      recognized here to be useful for species delimitation: the presence or absence of
      small rhizoid-like groups of hairs on the thallus surface, structure and
      arrangement of HLs on both surfaces either alternate or irregular, and
      arrangement of the alternating HLs between both surfaces in equal or unequal
      distance. The evolutionary trajectory of these and six other morphological
      characters used in species delineation was traced on the phylogenetic tree. 

PMID- 27028248
TI  - Commentary: Old Perceptions Were Too Limited.

PMID- 27028250
TI  - The Down Syndrome Information Act: Balancing the Advances of Prenatal Testing
      Through Public Policy.
AB  - Since the dawn of prenatal testing in the 1970s, concerns have been raised over
      its administration to respect a mother's autonomy as well as the expressive
      critique against those with the tested-for condition. Advances in prenatal
      testing have made it such that more mothers than ever are given a test result of
      Down syndrome, yet are not provided the rest of the information recommended by
      professional guidelines. In response, first federal legislation and then,
      increasingly, state legislation is requiring that this information be provided to
      expectant mothers. Though receiving broad bipartisan support in passage, some of
      the statutes have received criticism. These public policy measures will be
      surveyed and evaluated as to their relative merits and limitations. 

PMID- 27028251
TI  - Perceptions of Health and Healthcare of People With Intellectual and
      Developmental Disabilities in Medicaid Managed Care.
AB  - This study examined perceptions of health and healthcare of people with
      intellectual and developmental disabilities (IDD) receiving Medicaid Managed
      Care. Exploratory, semistructured interviews were conducted with 23 participants.
      Findings indicate that participants generally expressed being in good health and
      defined good health as (a) absence of pain, disease, and symptoms; (b) adherence
      to or not requiring treatment; (c) physical self-care; (d) mental or spiritual
      self-care; and (e) ability to perform the activities one wants to do.
      Participants conceptualized healthcare as (a) ensuring needs are met through
      access to services, (b) obtaining quality services, (c) navigating the healthcare
      system successfully, and (d) receiving humanizing healthcare. This study has
      implications for improving healthcare and communications between people with IDD
      and healthcare providers. 

PMID- 27028252
TI  - Individuals With Disabilities Who Have Diabetes: Do We Have Targeted
      Interventions?
AB  - According to 2010 data from the Centers for Disease Control and Prevention (CDC),
      diabetes is the seventh leading cause of death in the United States. It is
      assumed that various diabetes interventions are available to help individuals
      manage this chronic disease, but that is not the case. The literature is scant
      regarding interventions focused on people with disabilities who have diabetes.
      The purpose of this article is to review interventions specifically focused on
      people with disabilities who have diabetes and to discuss the effect of these
      interventions on this population. 

PMID- 27028253
TI  - "Teaches People That I'm More Than a Disability": Using Nominal Group Technique
      in Patient-Oriented Research for People With Intellectual and Developmental
      Disabilities.
AB  - Individuals with intellectual and developmental disabilities (IDD) have complex
      healthcare needs, which are often unmet. Nominal group technique (NGT) uses a
      mixed-methods approach, which may engage the IDD population in the research
      process in a person-centered manner and address the shortcomings of traditional
      research methods with this population. NGT was used with a group of 10 self
      advocates to evaluate a series of healthcare tools created by and for individuals
      with IDD. Participants provided helpful input about the strengths of these tools
      and suggestions to improve them. NGT was found to be an effective way to engage
      all participants in the research process. 

PMID- 27028254
TI  - Frailty as a Predictor of Institutionalization Among Adults With Intellectual and
      Developmental Disabilities.
AB  - Adults with intellectual and developmental disabilities (IDD) frequently become
      frail earlier than the general population, resulting in higher care needs. This
      population is at risk for institutionalization, or re-institutionalization, into
      long-term care (LTC). Using a retrospective cohort design to follow 3,034
      individuals (18-99 years) living in Ontario, Canada, and assessed with the
      Resident Assessment Instrument-Home Care, individuals were characterized with a
      frailty index (FI) for persons with IDD. Survival analyses determined differences
      in rates of admission to LTC and survival in the community. Frail individuals had
      greater rates of admission than non-frail individuals, adjusted HR = 2.19, 95% CI
      [1.81, 2.64]. The FI predicts institutionalization. 

PMID- 27028255
TI  - Evaluating the Implementation of Health Checks for Adults With Intellectual and
      Developmental Disabilities in Primary Care: The Importance of Organizational
      Context.
AB  - Compared to other adults, those with intellectual and developmental disabilities
      have more health issues, yet are less likely to receive preventative care. One
      strategy that has shown success in increasing prevention activities and early
      detection of illness is the periodic comprehensive health assessment (the health
      check). Effectively moving evidence into practice is a complex process that often
      receives inadequate attention. This qualitative study evaluates the
      implementation of the health check at two primary-care clinics in Ontario,
      Canada, and the influence of the clinic context on implementation decisions. Each
      clinic implemented the same core components; however, due to contextual
      differences, some components were operationalized differently. Adapting to the
      setting context is important to ensuring successful and sustainable
      implementation. 

PMID- 27028256
TI  - From Nonissue to Healthcare Crisis: A Historical Review of Aging and Dying With
      an Intellectual and Developmental Disability.
AB  - Individuals with intellectual and developmental disabilities are living
      unprecedentedly longer lives primarily due to the long-term benefits of the
      deinstitutionalization movement and widespread improvements in health outcomes.
      However, the consequences of this protracted aging process are significant,
      complex, and often poor not only for the individuals and their caregivers but for
      the mainstream healthcare community. This article will explore, utilizing a
      constructionist perspective, how these challenges evolved from a nonissue to an
      impending crisis in less than 25 years. Additionally, present-day efforts by
      researchers, policymakers, and practitioners to address these challenges will be
      explored and recommendations will be made for future directions. 

PMID- 27028260
TI  - Synthesis of some novel 2-substituted benzothiazole derivatives containing
      benzylamine moiety as monoamine oxidase inhibitory agents.
AB  - In the present work, 12 new 2-(5-substituted-benzothiazol-2-ylsulfanyl)-N
      (substitutedbenzyl)-N-(4-substitutedphenyl) acetamide derivatives (4a-l) was
      designed and synthesized. The structures of the synthesized compounds were
      clarified using Fourier transform infrared spectroscopy (FTIR), proton nuclear
      magnetic resonance ((1)H-NMR), carbon-13 nuclear magnetic resonance ((13)C-NMR)
      and high-resolution mass spectrometry (HRMS) spectral data. Purity of synthesized
      compounds was checked by high-performance liquid chromatography (HPLC) analyses
      and purity ratio was found between 96.5-99.9%. The inhibitory activity of the
      compounds against MAO-A and MAO-B enzymes was evaluated by using in vitro
      flurometric method in which kynuramine was used as a substrate. Most of the
      compounds exhibited more selective inhibitory activity towards monoamine oxidase
      B (MAO-B) than monoamine oxidase A (MAO-A). Compound 4h was determined as the
      most potent compound against both enzyme types. The MAO-B enzyme kinetic of the
      compound 4h was studied and nature of MAO-B inhibition, caused by this compound,
      was investigated. The graphical analysis of steady-state inhibition data
      indicated that compound 4h is a mixed type inhibitor. Theoretical calculation of
      absorption, distribution, metabolism, excretion (ADME) properties for the
      synthesized compounds was also carried out and observed data supported the
      potential of compound 4h. 

PMID- 27028259
TI  - Association of polymorphisms in APOE and LOXL1 with pseudoexfoliation syndrome
      and pseudoexfoliation glaucoma in a Turkish population.

PMID- 27028261
TI  - Alcohol use and menopause.
AB  - Clinicians should periodically assess their menopausal patients' alcohol use.
      Specific health hazards from excessive alcohol consumption, as well as potential
      benefits of low-level consumption (for cardiovascular disease, bone health, and
      type 2 diabetes), should be discussed with their patients who drink. The
      information in this Practice Pearl can help clinicians provide evidence-based
      guidance about alcohol consumption and its relationship to common health
      concerns. 

PMID- 27028262
TI  - Never Say Never Again.

PMID- 27028263
TI  - Broad-Spectrum Antimicrobial Star Polycarbonates Functionalized with Mannose for
      Targeting Bacteria Residing inside Immune Cells.
AB  - In this study, a series of star-shaped polycarbonates are synthesized by metal
      free organocatalytic ring-opening polymerization of benzyl chloride (BnCl) and
      mannose-functionalized cyclic carbonate monomers (MTC-BnCl and MTC-ipman) with
      heptakis-(2,3-di-O-acetyl)-beta-cyclodextrin (DA-beta-CD) as macroinitiator. The
      distributions and compositions of pendent benzyl chloride and protected mannose
      group (ipman) units are facilely modulated by varying the polymerization sequence
      and feed ratio of the monomers, allowing precise control over the molecular
      composition, and the resulting polymers have narrow molecular weight
      distribution. After deprotection of ipman groups and quaternization with various
      N,N-dimethylalkylamines, these star polymers with optimized compositions of
      cationic and mannose groups in block and random forms exhibit strong bactericidal
      activity and low hemolysis. Furthermore, the optimal mannose-functionalized
      polymer demonstrates mannose receptor-mediated intracellular bactericidal
      activity against BCG mycobacteria without inducing cytotoxicity on mammalian
      cells at the effective dose. Taken together, the materials designed in this study
      have potential use as antimicrobial agents against diseases such as tuberculosis,
      which is caused by intracellular bacteria.

PMID- 27028264
TI  - Observed Cognitive Performance and Deviation From Familial Cognitive Aptitude at
      Age 16 Years and Ages 18 to 20 Years and Risk for Schizophrenia and Bipolar
      Illness in a Swedish National Sample.
AB  - IMPORTANCE: Proposal of an innovative approach to clarify the mechanism through
      which poor cognitive performance in adolescence impacts risk for schizophrenia
      (SZ). OBJECTIVE: To determine whether the developmental processes that predispose
      to SZ are better reflected by the observed cognitive performance in adolescence
      or the deviation of that performance from the individual's familial cognitive
      aptitude (FCA). DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort design.
      Risk for SZ and bipolar illness (BPI) are predicted by school achievement (SA) at
      age 16 years and IQ at ages 18 to 20 years and the deviation of that performance
      from an individual's FCA. Familial cognitive aptitude is calculated from the SA,
      IQ, and educational attainment in biological relatives. MAIN OUTCOMES AND
      MEASURES: Diagnoses of SZ or BPI in the Swedish Hospital Discharge Register and
      the Swedish Outpatient Register. RESULTS: Participants were 996 886 individuals
      with recorded SA and 106 187 individuals with recorded IQ born in Sweden between
      January 1, 1972, and December 31, 1990, with sufficient numbers of biological
      relatives to calculate their FCA. The first cohort is 48.7% female, and the
      second is all male. Risk for SZ was strongly predicted by the deviation of SA
      from the FCA (hazard ratio [HR], 0.56; 95% CI, 0.49-0.63) but not with the
      observed SA (HR, 1.01; 95% CI, 0.91-1.13). Similar results were obtained for IQ
      (HR, 0.53; 95% CI, 0.37-0.77 for the deviation from the FCA and HR, 1.07; 95% CI,
      0.78-1.46 for the observed IQ). After matching SZ and control probands on
      cognitive performance, the siblings of the SZ probands had SA and IQs that did
      not differ from population means and were significantly higher in cognitive
      performance than for the siblings of control probands. Correlations in SA and IQs
      between the pre-SZ probands and their siblings were significantly lower than
      those observed between the matched control probands and their siblings. Risk for
      BPI was more weakly predicted by deviations from the FCA. No differences were
      found in the SA and IQs of siblings of BPI vs matched control probands.
      CONCLUSIONS AND RELEVANCE: The neurodevelopmental processes that predispose to SZ
      are not well reflected by cognitive performance per se but rather are much better
      indexed by the deviation in cognitive ability from that expected from an
      individual's FCA. The lowered cognitive performance in the pre-SZ probands
      appears to arise from qualitative developmental impairments rather than an
      unlucky combination of the genetic and environmental risk factors widely
      distributed within their family.

PMID- 27028266
TI  - Josephson current through a quantum dot coupled to a Majorana zero mode.
AB  - Employing the Green's function method, we investigate the Josephson current
      through a quantum dot side coupled to a topological superconducting nanowire
      sustaining a pair of Majorana zero modes. It is found that the Josephson current
      is blocked when the quantum dot is side coupled to a superconducting nanowire in
      a topologically trivial phase. However, when the topological superconducting
      nanowire transitions from a topologically trivial to a topologically non-trivial
      phase, an Andreev bound state arises at the zero Fermi energy of the quantum dot
      due to leakage of the Majorana zero mode. Thus a Josephson current can be induced
      by leakage of the Majorana zero mode into the quantum dot. The Josephson current
      shows a plateau-like structure and a clear-cut trivial/non-trivial phase
      transition, as a function of a Zeeman field imposed on the system. The transition
      and plateau-like structure can be used to probe the existence of the Majorana
      zero mode. The current-phase relation has also been studied. 

PMID- 27028265
TI  - A novel membrane anchor for FtsZ is linked to cell wall hydrolysis in Caulobacter
      crescentus.
AB  - In most bacteria, the tubulin-like GTPase FtsZ forms an annulus at midcell (the Z
      ring) which recruits the division machinery and regulates cell wall remodeling.
      Although both activities require membrane attachment of FtsZ, few membrane
      anchors have been characterized. FtsA is considered to be the primary membrane
      tether for FtsZ in bacteria, however in Caulobacter crescentus, FtsA arrives at
      midcell after stable Z-ring assembly and early FtsZ-directed cell wall synthesis.
      We hypothesized that additional proteins tether FtsZ to the membrane and
      demonstrate that in C. crescentus, FzlC is one such membrane anchor. FzlC
      associates with membranes directly in vivo and in vitro and recruits FtsZ to
      membranes in vitro. As for most known membrane anchors, the C-terminal peptide of
      FtsZ is required for its recruitment to membranes by FzlC in vitro and midcell
      recruitment of FzlC in cells. In vivo, overproduction of FzlC causes cytokinesis
      defects whereas deletion of fzlC causes synthetic defects with dipM, ftsE and
      amiC mutants, implicating FzlC in cell wall hydrolysis. Our characterization of
      FzlC as a novel membrane anchor for FtsZ expands our understanding of FtsZ
      regulators and establishes a role for membrane-anchored FtsZ in the regulation of
      cell wall hydrolysis.

PMID- 27028267
TI  - Salmonella Typhimurium and Outbreaks of Egg-Associated Disease in Australia, 2001
      to 2011.
AB  - INTRODUCTION: Salmonellosis is a significant public health problem, with eggs
      frequently identified as a food vehicle during outbreak investigations.
      Salmonella enterica serovar Typhimurium and Salmonella enterica serovar
      Enteritidis are the two most frequently identified causes of egg-associated
      disease in industrialized countries. In Australia, a comprehensive review of egg
      associated outbreaks has not been previously undertaken. METHODS: Using a
      national register of foodborne outbreaks, we undertook a descriptive review of
      egg-associated outbreaks between 2001 and 2011. Included in our review was
      additional detail from the findings of trace back investigations conducted to the
      farm level. Evidence classifications were developed and applied to each outbreak
      based on descriptive and analytical epidemiology, food safety investigations, and
      microbiological testing of clinical, food, and trace back-derived samples.
      RESULTS: Over the study period, the proportion of foodborne Salmonella outbreaks
      linked to eggs increased significantly (p < 0.001). In total, 166 outbreaks were
      identified, with 90% caused by Salmonella Typhimurium. The majority of outbreaks
      were linked to commercial food providers, with raw egg use the major contributing
      factor. These events resulted in more than 3200 cases, more than 650
      hospitalizations, and at least 4 deaths. Fifty-four percent of investigations
      used analytical epidemiology, food microbiology, and trace back microbiology to
      demonstrate links between human illness and eggs. Trace back investigations
      identified S. enterica indistinguishable from outbreak-associated clinical or
      food samples on 50% of sampled egg farms. CONCLUSION: Effective control of egg
      associated salmonellosis remains a challenge in Australia, with Salmonella
      Typhimurium dominating as the causative serotype in outbreak events. Although
      outbreaks predominantly occur in the settings of restaurants, the high recovery
      rate of indistinguishable Salmonella on epidemiologically implicated egg farms
      suggests that further efforts to minimize infection pressure at the primary
      production level are needed in Australia.

PMID- 27028268
TI  - Sandwich-Architectured Poly(lactic acid)-Graphene Composite Food Packaging Films.
AB  - Biodegradable food packaging promises a more sustainable future. Among the many
      different biopolymers used, poly(lactic acid) (PLA) possesses the good mechanical
      property and cost-effectiveness necessary of a biodegradable food packaging.
      However, PLA food packaging suffers from poor water vapor and oxygen barrier
      properties compared to many petroleum-derived ones. A key challenge is,
      therefore, to simultaneously enhance both the water vapor and oxygen barrier
      properties of the PLA food packaging. To address this issue, we design a sandwich
      architectured PLA-graphene composite film, which utilizes an impermeable reduced
      graphene oxide (rGO) as the core barrier and commercial PLA films as the outer
      protective encapsulation. The synergy between the barrier and the protective
      encapsulation results in a significant 87.6% reduction in the water vapor
      permeability. At the same time, the oxygen permeability is reduced by two orders
      of magnitude when evaluated under both dry and humid conditions. The excellent
      barrier properties can be attributed to the compact lamellar microstructure and
      the hydrophobicity of the rGO core barrier. Mechanistic analysis shows that the
      large rGO lateral dimension and the small interlayer spacing between the rGO
      sheets have created an extensive and tortuous diffusion pathway, which is up to
      1450-times the thickness of the rGO barrier. In addition, the sandwiched
      architecture has imbued the PLA-rGO composite film with good processability,
      which increases the manageability of the film and its competency to be tailored.
      Simulations using the PLA-rGO composite food packaging film for edible oil and
      potato chips also exhibit at least eight-fold extension in the shelf life of
      these oxygen and moisture sensitive food products. Overall, these qualities have
      demonstrated the high potential of a sandwich-architectured PLA-graphene
      composite film for food packaging applications. 

PMID- 27028269
TI  - Acute Metabolic Changes Associated With Analgesic Drugs: An MR Spectroscopy
      Study.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) is used to measure
      brain metabolites. Limited data exist on the analgesic-induced spectroscopy
      response. This was an explorative study with the aims to investigate the central
      effects of two analgesic drugs, an opioid and a selective serotonin and
      norepinephrine reuptake inhibitor, and to explore the association between
      metabolite changes and the analgesic effect and side effects. METHODS: Single
      voxel proton spectroscopy measurements were performed in the anterior cingulate
      cortex, insula and prefrontal cortex in 20 healthy subjects before and after
      treatment for 5 days with oxycodone (eight doses of 10 mg extended release),
      venlafaxine (eight doses of 37.5 mg extended release) or placebo in a randomized
      double-blind fashion. The metabolites of glutamate, N-acetylaspartate, and myo
      inositol were analyzed in ratios to creatine. RESULTS: Including all areas, the
      glutamate/creatine ratio was decreased (P < .05) with 8.4% +/- 0.3% after
      oxycodone treatment (P = .02) and 6.6% +/- 0.4% after venlafaxine treatment (P =
      .07) as compared to placebo. No statistical significant differences in treatment
      effects across the areas were found (P = .6). No treatment effect was seen for N
      acetylaspartate/creatine or myo-inositol/creatine ratios (all P > .05). No
      associations between treatment induced glutamate/creatine changes and the
      analgesic effect and side effects were demonstrated (all P > .05). CONCLUSIONS:
      MRS can be used to detect brain metabolites following acute analgesic treatments
      and glutamate is central in these mechanisms. Consequently, MRS might be a
      valuable tool to objectively evaluate analgesic effects and a potential biomarker
      to predict treatment outcomes and more research is needed.

PMID- 27028271
TI  - Evolving RNA Virus Pandemics: HIV, HCV, Ebola, Dengue, Chikunguya, and now Zika!
AB  - The Zika virus (ZIKV), a flavivirus related to yellow fever, dengue, and West
      Nile, originated in the Zika forest in Uganda and was discovered in a rhesus
      monkey in 1947. The disease now has "explosive" pandemic potential, with
      outbreaks in Africa, Southeast Asia, the Pacific Islands, and the Americas. To
      date, the CDC has issued travel alerts for at least 30 countries and territories
      in Latin America, the Caribbean, Polynesia, and Cape Verde in Africa. 

PMID- 27028270
TI  - Accuracy of advanced cancer patients' life expectancy estimates: The role of race
      and source of life expectancy information.
AB  - BACKGROUND: The objective of this study was to examine the source of advanced
      cancer patients' information about their prognosis and determine whether this
      source of information could explain racial disparities in the accuracy of
      patients' life expectancy estimates (LEEs). METHODS: Coping With Cancer was a
      prospective, longitudinal, multisite study of terminally ill cancer patients
      followed until death. In structured interviews, patients reported their LEEs and
      the sources of these estimates (ie, medical providers, personal beliefs,
      religious beliefs, and other). The accuracy of LEEs was calculated through a
      comparison of patients' self-reported LEEs with their actual survival. RESULTS:
      The sample for this analysis included 229 patients: 31 black patients and 198
      white patients. Only 39.30% of the patients estimated their life expectancy
      within 12 months of their actual survival. Black patients were more likely to
      have an inaccurate LEE than white patients. A minority of the sample (18.3%)
      reported that a medical provider was the source of their LEEs; none of the black
      patients (0%) based their LEEs on a medical provider. Black race remained a
      significant predictor of an inaccurate LEE, even after the analysis had been
      controlled for sociodemographic characteristics and the source of LEEs.
      CONCLUSIONS: The majority of advanced cancer patients have an inaccurate
      understanding of their life expectancy. Black patients with advanced cancer are
      more likely to have an inaccurate LEE than white patients. Medical providers are
      not the source of information for LEEs for most advanced cancer patients and
      especially for black patients. The source of LEEs does not explain racial
      differences in LEE accuracy. Additional research into the mechanisms underlying
      racial differences in prognostic understanding is needed. Cancer 2016;122:1905
      12. (c) 2016 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- 27028272
TI  - New Insights into HIV-1 Persistence in Sanctuary Sites During Antiretroviral
      Therapy.
AB  - Current combinations of antiretroviral drugs for the treatment of HIV infection
      can successfully achieve and maintain long-term suppression of HIV-1 replication
      in plasma. Still, none of these therapies is capable of eradicating the virus
      from the long-lived cellular reservoir that represents the major barrier to HIV
      cure. 

PMID- 27028273
TI  - Educational Offerings and Technology.

PMID- 27028274
TI  - Abstracts of the 3rd International Meeting on Ischemia Reperfusion Injury in
      Transplantation - IMIRT 2016, Poitiers, France, 21-22 April 2016.

PMID- 27028275
TI  - Thinking of VACTERL-H? Rule out Fanconi Anemia according to PHENOS.
AB  - VACTERL-H association includes three of eight features: vertebral anomalies, anal
      atresia, congenital heart disease, tracheo-esophageal fistula, esophageal
      atresia, renal, limb anomalies, and hydrocephalus. The VACTERL-H phenotype among
      cases with FA is considered to be about 5%; the frequency of FA among patients
      with VACTERL-H is unknown. We examined 54 patients with FA in the National Cancer
      Institute Inherited Bone Marrow Failure Syndrome Cohort for features of VACTERL
      H, including imaging studies (radiology and ultrasound). Eighteen of the fifty
      four patients had three or more VACTERL-H features. The presence of VACTERL-H
      association in 33% of those with FA is much higher than the previous estimate of
      5% (P < 0.0001). We created the acronym PHENOS (Pigmentation, small Head, small
      Eyes, central Nervous system (not hydrocephalus), Otology, and Short stature)
      which includes all major phenotypic features of FA that are not in VACTERL-H;
      these findings were more frequent in the patients with FA who had VACTERL-H.
      Identification of any components of the VACTERL-H association should lead to
      imaging studies, and to consideration of the diagnosis of FA, particularly if the
      patient has radial ray and renal anomalies, as well as many features of PHENOS.
      There was no association of the presence or absence of VACTERL-H with development
      of cancer, stem cell transplant, or survival. Early diagnosis will lead to
      genetic counseling and early surveillance and management of complications of FA.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27028276
TI  - Evidence for increased motor cortical facilitation and decreased inhibition in
      atypical depression.
AB  - OBJECTIVE: Major depressive disorder (MDD) is a clinically heterogeneous
      condition. However, the role of cortical glutamate and gamma-aminobutyric acid
      (GABA) receptor-mediated activity, implicated in MDD pathophysiology, has not
      been explored in different MDD subtypes. Our aim was to assess the atypical and
      melancholic depression subtypes regarding potential differences in GABA and
      glutamate receptor-mediated activity through established transcranial magnetic
      stimulation (TMS) neurophysiological measures from the motor cortex. METHOD: We
      evaluated 81 subjects free of antidepressant medication, including 21 healthy
      controls and 20 patients with atypical, 20 with melancholic, and 20 with
      undifferentiated MDD. Single and paired-pulse TMS paradigms were used to evaluate
      intracortical facilitation (ICF), cortical silent period (CSP), and short
      intracortical inhibition (SICI), which index glutamate, GABAB receptor-, and
      GABAA receptor-mediated activity respectively. RESULTS: Patients with MDD
      demonstrated significantly decreased mean CSP values than healthy controls
      (Cohen's d = 0.22-0.3, P < 0.01 for all comparisons). Atypical depression
      presented a distinct cortical excitability pattern of decreased cortical
      inhibition and increased cortical facilitation, that is, an increased mean ICF
      and SICI ratios than other depression subtypes (d = 0.22-0.33, P < 0.01 for all
      comparisons). CONCLUSION: Different MDD subtypes may demonstrate different
      neurophysiology in relation to GABAA and glutamatergic activity. TMS as an
      investigational tool might be useful to distinguish between different MDD
      subtypes.

PMID- 27028277
TI  - Biases in obesity research: Identify, correct, endorse, or abandon effort?

PMID- 27028278
TI  - Placebo effects in obesity research.

PMID- 27028279
TI  - Weight change among people randomized to minimal intervention control groups in
      weight loss trials.
AB  - OBJECTIVE: Evidence on the effectiveness of behavioral weight management programs
      often comes from uncontrolled program evaluations. These frequently make the
      assumption that, without intervention, people will gain weight. The aim of this
      study was to use data from minimal intervention control groups in randomized
      controlled trials to examine the evidence for this assumption and the effect of
      frequency of weighing on weight change. METHODS: Data were extracted from minimal
      intervention control arms in a systematic review of multicomponent behavioral
      weight management programs. Two reviewers classified control arms into three
      categories based on intensity of minimal intervention and calculated 12-month
      mean weight change using baseline observation carried forward. Meta-regression
      was conducted in STATA v12. RESULTS: Thirty studies met the inclusion criteria,
      twenty-nine of which had usable data, representing 5,963 participants allocated
      to control arms. Control arms were categorized according to intensity, as
      offering leaflets only, a single session of advice, or more than one session of
      advice from someone without specialist skills in supporting weight loss. Mean
      weight change at 12 months across all categories was -0.8 kg (95% CI -1.1 to 
      0.4). In an unadjusted model, increasing intensity by moving up a category was
      associated with an additional weight loss of -0.53 kg (95% CI -0.96 to -0.09).
      Also in an unadjusted model, each additional weigh-in was associated with a
      weight change of -0.42 kg (95% CI -0.81 to -0.03). However, when both variables
      were placed in the same model, neither intervention category nor number of weigh
      ins was associated with weight change. CONCLUSIONS: Uncontrolled evaluations of
      weight loss programs should assume that, in the absence of intervention, their
      population would weigh up to a kilogram on average less than baseline at the end
      of the first year of follow-up.

PMID- 27028281
TI  - Promoting young children's engagement in organized extracurricular activities:
      'Tiger parenting' or obesity prevention?

PMID- 27028280
TI  - Common scientific and statistical errors in obesity research.
AB  - This review identifies 10 common errors and problems in the statistical analysis,
      design, interpretation, and reporting of obesity research and discuss how they
      can be avoided. The 10 topics are: 1) misinterpretation of statistical
      significance, 2) inappropriate testing against baseline values, 3) excessive and
      undisclosed multiple testing and "P-value hacking," 4) mishandling of clustering
      in cluster randomized trials, 5) misconceptions about nonparametric tests, 6)
      mishandling of missing data, 7) miscalculation of effect sizes, 8) ignoring
      regression to the mean, 9) ignoring confirmation bias, and 10) insufficient
      statistical reporting. It is hoped that discussion of these errors can improve
      the quality of obesity research by helping researchers to implement proper
      statistical practice and to know when to seek the help of a statistician. 

PMID- 27028283
TI  - Reducing relative food reinforcement in infants by an enriched music experience.
AB  - OBJECTIVE: The reinforcing value of food may be established early in life.
      Research shows that infant weight status is related to the relative reinforcing
      value of food versus non-food alternatives (food reinforcing ratio, FRR). The
      purpose of this pilot study was to assess the effects of a 6-week music
      enhancement program (Music Together(r), n = 14) versus an active play date
      control group (n = 13) on the FRR in 9- to 16-month-old infants who were high in
      relative food reinforcement. METHODS: Participating parents and infants attended
      six weekly 45-min group classes. Parents in the music group and the play date
      group were encouraged to listen to the Music Together program CD or play with the
      play date group's toy with their infants at home, respectively. RESULTS: Intent
      to-treat analysis showed a decrease in FRR for infants in the music group (mean
      +/- SD: -0.13 +/- 0.13) in comparison to a slight increase in the control group
      (0.04 +/- 0.11) (F[1, 24]  = 11.86, P = 0.002). CONCLUSIONS: These findings
      provide evidence that relative reinforcing value of food can be reduced by
      promoting alternative reinforcers at an early age.

PMID- 27028284
TI  - Heavy childhood television use persists into young adulthood and is associated
      with increased BMI.
AB  - OBJECTIVE: To test whether TV use has both concurrent effects on body mass index
      (BMI) at the time of survey interviews and long-term, enduring effects via the
      promotion of future levels of TV use. METHODS: Two waves of survey data from the
      Panel Study of Income Dynamics were used to test relationships between TV use and
      BMI among a nationally representative sample of children and their parents (n =
      1,421). Path analysis was used to model effects of childhood (1997) levels of TV
      use and BMI on the same variables 14 years later (2011). RESULTS: Path analysis
      showed childhood TV use was associated positively with childhood BMI (beta =
      0.08, P < 0.05), and young adult TV use was related positively to young adult BMI
      (beta = 0.10, P < 0.01). Heavy childhood TV use also persisted into young
      adulthood (beta = 0.15, P < 0.001), indirectly increasing young adult BMI (beta =
      0.02, P < 0.05). CONCLUSIONS: Heavy childhood TV users tend to become heavy young
      adult users. The continuation of TV behavior from childhood to young adulthood
      independently increases BMI.

PMID- 27028282
TI  - Impact of intensive lifestyle intervention on preference-based quality of life in
      type 2 diabetes: Results from the Look AHEAD trial.
AB  - OBJECTIVE: To assess the effect of an intensive lifestyle intervention (ILI)
      compared with standard diabetes support and education (DSE) on preference-based
      health-related quality of life (HRQOL) in persons with overweight or obesity and
      type 2 diabetes. METHODS: Look AHEAD was a multisite, randomized trial of 5,145
      participants assigned to ILI or DSE. Four instruments were administered during
      the trial: Feeling Thermometer (FT), Health Utilities Index Mark 2 (HUI2), Health
      Utilities Index Mark 3 (HUI3), and Short Form 6D (SF-6D). Linear mixed effect
      models were used to estimate the mean difference in preference scores by
      treatment group for 9 years. RESULTS: The ILI had higher mean FT (0.019, 95% CI,
      0.015-0.024, P < 0.001) and SF-6D (0.011, 95% CI, 0.006-0.014, P < 0.001) scores
      than the DSE. No significant group differences were observed for the HUI2 (0.004,
      95% CI, -0.003 to 0.010, P = 0.23) and HUI3 (0.004, -0.004 to 0.012, P = 0.36).
      In year 1, the ILI had higher mean preference scores for all instruments.
      Thereafter, the increases remained significant only for FT and SF-6D, and the
      effects also become smaller. CONCLUSIONS: ILI aimed at reducing body weight among
      persons with overweight or obesity and type 2 diabetes improves preference-based
      HRQOL in the short term, but its long-term effect is unclear.

PMID- 27028285
TI  - Erratum: Overexpression of neuropeptide Y in the dorsomedial hypothalamus causes
      hyperphagia and obesity in rats.

PMID- 27028287
TI  - Research on rehabilitation interventions for adults living with HIV: a scoping
      review.
AB  - The aim of this paper is to use a scoping review to investigate the extent,
      range, and nature of research on rehabilitation interventions for adults living
      with HIV. Electronic databases (MEDLINE, EMBASE, CINAHL, AMED, and PsychINFO) and
      reference lists of the included articles were searched. Authors were emailed when
      possible for unavailable articles. A total of 897 titles and abstracts were
      retrieved. Thirty-three articles were included. There were 27 different
      rehabilitation interventions delivered by 18 professions. The studies were
      completed in four different countries. Most studies were published in 2008. A
      randomized-controlled trial was the most used method. The nature of the studies
      was analyzed according to the three-core concepts of the International
      Classification of Functioning, Disability and Health: 28 studies addressed
      impairments; six studies addressed activity limitations; and 14 studies addressed
      participation restrictions. This scoping study advances the knowledge of research
      on rehabilitation interventions for adults living with HIV. More research on
      rehabilitation interventions is needed in sub-Saharan Africa and other low-income
      and middle-income countries to ensure that these individuals are receiving the
      best possible care. There is a need for the HIV field to recognize the important
      contribution of rehabilitation toward the HIV care continuum. 

PMID- 27028286
TI  - EUROmediCAT signal detection: an evaluation of selected congenital anomaly
      medication associations.
AB  - AIMS: To evaluate congenital anomaly (CA)-medication exposure associations
      produced by the new EUROmediCAT signal detection system and determine which
      require further investigation. METHODS: Data from 15 EUROCAT registries (1995
      2011) with medication exposures at the chemical substance (5th level of Anatomic
      Therapeutic Chemical classification) and chemical subgroup (4th level) were
      analysed using a 50% false detection rate. After excluding antiepileptics,
      antidiabetics, antiasthmatics and SSRIs/psycholeptics already under
      investigation, 27 associations were evaluated. If evidence for a signal persisted
      after data validation, a literature review was conducted for prior evidence of
      human teratogenicity. RESULTS: Thirteen out of 27 CA-medication exposure signals,
      based on 389 exposed cases, passed data validation. There was some prior evidence
      in the literature to support six signals (gastroschisis and
      levonorgestrel/ethinylestradiol (OR 4.10, 95% CI 1.70-8.53; congenital heart
      disease/pulmonary valve stenosis and nucleoside/tide reverse transcriptase
      inhibitors (OR 5.01, 95% CI 1.99-14.20/OR 28.20, 95% CI 4.63-122.24); complete
      absence of a limb and pregnen (4) derivatives (OR 6.60, 95% CI 1.70-22.93);
      hypospadias and pregnadien derivatives (OR 1.40, 95% CI 1.10-1.76); hypospadias
      and synthetic ovulation stimulants (OR 1.89, 95% CI 1.28-2.70). Antipropulsives
      produced a signal for syndactyly while the literature revealed a signal for
      hypospadias. There was no prior evidence to support the remaining six signals
      involving the ordinary salt combinations, propulsives, bulk-forming laxatives,
      hydrazinophthalazine derivatives, gonadotropin releasing hormone analogues and
      selective serotonin agonists. CONCLUSION: Signals which strengthened prior
      evidence should be prioritized for further investigation, and independent
      evidence sought to confirm the remaining signals. Some chance associations are
      expected and confounding by indication is possible.

PMID- 27028288
TI  - Cross-cultural validation of the Italian version of the Cumulated Ambulation
      Score.
AB  - Hip fractures are common in elderly patients, and walking impairment is a
      frequent complication. The Cumulated Ambulation Score (CAS) is a validated
      functional scale used to monitor easily three basic mobility activities in
      patients with hip fracture. The aim of this study was to translate, cross
      cultural adapt, and validate the CAS in the Italian language (CAS-I). The
      translation was carried out according to recommended guidelines. The final
      version of the CAS-I was administered to 80 geriatric patients with hip fracture
      admitted to a Traumatology Unit, and allowed full weight-bearing after treatment
      with hemiarthroplasty. Two raters evaluated each patient 2 days after surgery and
      then after 3 months. Statistical methods included Cronbach's alpha coefficient
      for the scale's internal consistency; the total agreement; and the kappa
      coefficient for the inter-rater reliability. The concurrent validity of the scale
      was determined by comparing the total CAS-I (0-6 points) with the Index of
      Independence in Activities of Daily Living score (0-4 points). Internal
      consistency and inter-rater reliability of the CAS, evaluated with Cronbach's
      alpha and kappa, respectively, were above 0.84 and 0.94. The SE of measurement
      for the total CAS-I (0-6 points) 2 days and 3 months after surgery were 0.03 and
      0.13 points, respectively. The CAS-I showed a significant correlation with the
      first four items of the Activities of Daily Living score scale (r>=0.85,
      P<0.001). This study confirms the validity of the CAS-I for patients with a
      hemiarthroplasty after hip fracture and provides additional evidence of the
      psychometric properties of the scale. We suggest that the official CAS-I version
      be used in other settings to evaluate the basic mobility in patients with hip
      fracture. 

PMID- 27028289
TI  - Soil organic matter content effects on dermal pesticide bioconcentration in
      American toads (Bufo americanus).
AB  - Pesticides have been implicated as a major factor in global amphibian declines
      and may pose great risk to terrestrial phase amphibians moving to and from
      breeding ponds on agricultural landscapes. Dermal uptake from soil is known to
      occur in amphibians, but predicting pesticide availability and bioconcentration
      across soil types is not well understood. The present study was designed to
      compare uptake of 5 current-use pesticides (imidacloprid, atrazine, triadimefon,
      fipronil, and pendimethalin) in American toads (Bufo americanus) from exposure on
      soils with significant organic matter content differences (14.1% = high organic
      matter and 3.1% = low organic matter). We placed toads on high- or low-organic
      matter soil after applying individual current-use pesticides on the soil surface
      for an 8-h exposure duration. Whole body tissue homogenates and soils were
      extracted and analyzed using liquid chromatography-mass spectrometry to determine
      pesticide tissue and soil concentration, as well as bioconcentration factor in
      toads. Tissue concentrations were greater on the low-organic matter soil than the
      high-organic matter soil across all pesticides (average +/- standard error; 1.23
      +/- 0.35 ppm and 0.78 +/- 0.23 ppm, respectively), and bioconcentration was
      significantly higher for toads on the low-organic matter soil (analysis of
      covariance p = 0.002). Soil organic matter is known to play a significant role in
      the mobility of pesticides and bioavailability to living organisms. Agricultural
      soils typically have relatively lower organic matter content and serve as a
      functional habitat for amphibians. The potential for pesticide accumulation in
      amphibians moving throughout agricultural landscapes may be greater and should be
      considered in conservation and policy efforts. Environ Toxicol Chem 2016;35:2734
      2741. (c) 2016 SETAC.

PMID- 27028290
TI  - Modular organisation of inducer recognition and allostery in the tetracycline
      repressor.
AB  - Induction of the tetracycline repressor (TetR) results from antibiotic-dependent
      changes in the relative positioning of the DNA-binding domains within the
      promoter-associated repressor dimer, but the key determinants of this allosteric
      effect remain poorly characterised. Intriguingly, previous mutational analyses of
      the tetracycline-interacting site revealed a lack of correlation between residual
      affinity and induction propensity, suggesting that some of the residues in
      contact with the antibiotic primarily act in ligand recognition and retention,
      whereas others are required to transmit the allosteric signal. Here, we provide a
      structural basis for these observations via crystallographic analysis of the
      point mutants N82A, H100A, T103A and E147A in complex with the inducer 5a,6
      anhydrotetracycline. In conjunction with the available functional data, the four
      structures demonstrate that a trigger-like movement of the region between helices
      alpha6 and alpha7 towards and into the binding site plays a decisive role in the
      intramolecular communication process. In sharp contrast, residues lining the
      binding cavity proper have little or no influence on the allosteric mechanism as
      such. This nearly complete physical separation of ligand recognition and
      allostery will have allowed diverging TetR-like repressors to bind novel
      effectors while the existing induction mechanism remained intact. Consequently,
      the modularity described here may have been a key factor in the evolutionary
      success of the widespread and highly diversified repressor class. DATABASE:
      Structural data are available in the Protein Data Bank under the accession
      numbers 5FKK, 5FKL, 5FKM, 5FKN and 5FKO.

PMID- 27028291
TI  - Regulatory effects of cotranscriptional RNA structure formation and transitions.
AB  - RNAs, which play significant roles in many fundamental biological processes of
      life, fold into sophisticated and precise structures. RNA folding is a dynamic
      and intricate process, which conformation transition of coding and noncoding RNAs
      form the primary elements of genetic regulation. The cellular environment
      contains various intrinsic and extrinsic factors that potentially affect RNA
      folding in vivo, and experimental and theoretical evidence increasingly indicates
      that the highly flexible features of the RNA structure are affected by these
      factors, which include the flanking sequence context, physiochemical conditions,
      cis RNA-RNA interactions, and RNA interactions with other molecules. Furthermore,
      distinct RNA structures have been identified that govern almost all steps of
      biological processes in cells, including transcriptional activation and
      termination, transcriptional mutagenesis, 5'-capping, splicing, 3'
      polyadenylation, mRNA export and localization, and translation. Here, we briefly
      summarize the dynamic and complex features of RNA folding along with a wide
      variety of intrinsic and extrinsic factors that affect RNA folding. We then
      provide several examples to elaborate RNA structure-mediated regulation at the
      transcriptional and posttranscriptional levels. Finally, we illustrate the
      regulatory roles of RNA structure and discuss advances pertaining to RNA
      structure in plants. WIREs RNA 2016, 7:562-574. doi: 10.1002/wrna.1350 For
      further resources related to this article, please visit the WIREs website.

PMID- 27028292
TI  - Copper-Containing Anti-Biofilm Nanofiber Scaffolds as a Wound Dressing Material.
AB  - Copper particles were incorporated into nanofibers during the electrospinning of
      poly-D,L-lactide (PDLLA) and poly(ethylene oxide) (PEO). The ability of the
      nanofibers to prevent Pseudomonas aeruginosa PA01 and Staphylococcus aureus
      (strain Xen 30) to form biofilms was tested. Nanofibers containing copper
      particles (Cu-F) were thinner (326 +/- 149 nm in diameter), compared to
      nanofibers without copper (CF; 445 +/- 93 nm in diameter). The crystalline
      structure of the copper particles in Cu-F was confirmed by X-ray diffraction
      (XRD). Copper crystals were encapsulated, but also attached to the surface of Cu
      F, as shown scanning transmission electron microscopy (STEM) and transmission
      electron microscopy (TEM), respectively. The copper particles had no effect on
      the thermal degradation and thermal behaviour of Cu-F, as shown by
      thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC).
      After 48 h in the presence of Cu-F, biofilm formation by P. aeruginosa PA01 and
      S. aureus Xen 30 was reduced by 41% and 50%, respectively. Reduction in biofilm
      formation was ascribed to copper released from the nanofibers. Copper-containing
      nanofibers may be incorporated into wound dressings. 

PMID- 27028293
TI  - Minding the gap and moving forward in children's long-term conditions: A vital
      role for health psychology.

PMID- 27028294
TI  - Immune cell changes in response to a swimming training session during a 24-h
      recovery period.
AB  - Understanding the impact of training sessions on the immune response is crucial
      for the adequate periodization of training, to prevent both a negative influence
      on health and a performance impairment of the athlete. This study evaluated acute
      systemic immune cell changes in response to an actual swimming session, during a
      24-h recovery period, controlling for sex, menstrual cycle phases, maturity, and
      age group. Competitive swimmers (30 females, 15 +/- 1.3 years old; and 35 males,
      16.5 +/- 2.1 years old) performed a high-intensity training session. Blood
      samples were collected before, immediately after, 2 h after, and 24 h after
      exercise. Standard procedures for the assessment of leukogram by automated
      counting (Coulter LH 750, Beckman) and lymphocytes subsets by flow cytometry
      (FACS Calibur BD, Biosciences) were used. Subjects were grouped according to
      competitive age groups and pubertal Tanner stages. Menstrual cycle phase was
      monitored. The training session induced neutrophilia, lymphopenia, and a low
      eosinophil count, lasting for at least 2 h, independent of sex and maturity. At
      24 h postexercise, the acquired immunity of juniors (15-17 years old), expressed
      by total lymphocytes and total T lymphocytes (CD3(+)), was not fully recovered.
      This should be accounted for when planning a weekly training program. The
      observed lymphopenia suggests a lower immune surveillance at the end of the
      session that may depress the immunity of athletes, highlighting the need for
      extra care when athletes are exposed to aggressive environmental agents such as
      swimming pools. 

PMID- 27028295
TI  - Risk factors for mortality in end-stage kidney disease patients under online
      hemodiafiltration: three-year follow-up study.
AB  - The aim of this work was to evaluate the predictors of mortality in a group of
      end-stage kidney disease (ESRD) patients under dialysis, by performing a three
      year follow-up study. From the 236 patients included in this study, 54 patients
      died during the three-year follow-up period. Our data showed that the risk of
      death was higher in patients presenting lower levels of mean cell hemoglobin
      concentration, transferrin, and albumin. Our study showed that poor nutritional
      status and an inflammatory-induced iron depleted erythropoiesis are important
      factors for mortality in these patients. 

PMID- 27028297
TI  - A Complex Systems Approach to Causal Discovery in Psychiatry.
AB  - Conventional research methodologies and data analytic approaches in psychiatric
      research are unable to reliably infer causal relations without experimental
      designs, or to make inferences about the functional properties of the complex
      systems in which psychiatric disorders are embedded. This article describes a
      series of studies to validate a novel hybrid computational approach--the Complex
      Systems-Causal Network (CS-CN) method-designed to integrate causal discovery
      within a complex systems framework for psychiatric research. The CS-CN method was
      first applied to an existing dataset on psychopathology in 163 children
      hospitalized with injuries (validation study). Next, it was applied to a much
      larger dataset of traumatized children (replication study). Finally, the CS-CN
      method was applied in a controlled experiment using a 'gold standard' dataset for
      causal discovery and compared with other methods for accurately detecting causal
      variables (resimulation controlled experiment). The CS-CN method successfully
      detected a causal network of 111 variables and 167 bivariate relations in the
      initial validation study. This causal network had well-defined adaptive
      properties and a set of variables was found that disproportionally contributed to
      these properties. Modeling the removal of these variables resulted in significant
      loss of adaptive properties. The CS-CN method was successfully applied in the
      replication study and performed better than traditional statistical methods, and
      similarly to state-of-the-art causal discovery algorithms in the causal detection
      experiment. The CS-CN method was validated, replicated, and yielded both novel
      and previously validated findings related to risk factors and potential
      treatments of psychiatric disorders. The novel approach yields both fine-grain
      (micro) and high-level (macro) insights and thus represents a promising approach
      for complex systems-oriented research in psychiatry.

PMID- 27028298
TI  - Neuronal Nicotinic Acetylcholine Receptor Modulators Reduce Sugar Intake.
AB  - Excess sugar consumption has been shown to contribute directly to weight gain,
      thus contributing to the growing worldwide obesity epidemic. Interestingly,
      increased sugar consumption has been shown to repeatedly elevate dopamine levels
      in the nucleus accumbens (NAc), in the mesolimbic reward pathway of the brain
      similar to many drugs of abuse. We report that varenicline, an FDA-approved
      nicotinic acetylcholine receptor (nAChR) partial agonist that modulates dopamine
      in the mesolimbic reward pathway of the brain, significantly reduces sucrose
      consumption, especially in a long-term consumption paradigm. Similar results were
      observed with other nAChR drugs, namely mecamylamine and cytisine. Furthermore,
      we show that long-term sucrose consumption increases alpha4beta2 * and decreases
      alpha6beta2* nAChRs in the nucleus accumbens, a key brain region associated with
      reward. Taken together, our results suggest that nAChR drugs such as varenicline
      may represent a novel treatment strategy for reducing sugar consumption. 

PMID- 27028299
TI  - Migraine and the Risk of Suicide.
AB  - Rarely and tragically, migraineurs commit suicide or overdose on medications we
      prescribe. 

PMID- 27028300
TI  - Be Happy Not Sad for Your Youth: The Effect of Emotional Expression on Age
      Perception.
AB  - Perceived age is a psychosocial factor that can influence both with whom and how
      we choose to interact socially. Though intuition tells us that a smile makes us
      look younger, surprisingly little empirical evidence exists to explain how age
      irrelevant emotional expressions bias the subjective decision threshold for age.
      We examined the role that emotional expression plays in the process of judging
      one's age from a face. College-aged participants were asked to sort the emotional
      and neutral expressions of male facial stimuli that had been morphed across eight
      age levels into categories of either "young" or "old." Our results indicated that
      faces at the lower age levels were more likely to be categorized as old when they
      showed a sad facial expression compared to neutral expressions. Mirroring that,
      happy faces were more often judged as young at higher age levels than neutral
      faces. Our findings suggest that emotion interacts with age perception such that
      happy expression increases the threshold for an old decision, while sad
      expression decreases the threshold for an old decision in a young adult sample. 

PMID- 27028301
TI  - Management of coagulopathy associated with postpartum hemorrhage: guidance from
      the SSC of the ISTH.

PMID- 27028302
TI  - Adolescent sun protection at secondary school athletic sporting events - a
      misnomer.
AB  - OBJECTIVE: To observe the sun-protective practices of students and staff and
      related aspects of the physical environment at secondary school athletics days.
      METHODS: This observational study of 1,225 students and 215 adult supervisors
      examined the use of sun-protective items (hats, clothing coverage, sunglasses),
      sunscreen provision and shade. RESULTS: Sun-protective behaviour was poor with
      only 3% of students and 25% of adult supervisors wearing a sun-protective hat.
      Shade was not available to most students, either as competitors or while waiting
      to compete. Sunscreen provision was 50%. CONCLUSION: Portable shade for students
      waiting to compete should be available at competitive events. Students should be
      encouraged to wear sun-protective hats and clothing while not competing and
      SPF30+ broad-spectrum sunscreen should always be provided. Guidelines for adult
      supervisors should be developed so they role model appropriate sun protection.

PMID- 27028303
TI  - Two-Year Safety and Efficacy of Biodegradable Polymer Drug-Eluting Stent Versus
      Second-Generation Durable Polymer Drug-Eluting Stent in Patients With Acute
      Myocardial Infarction: Data from the Korea Acute Myocardial Infarction Registry
      (KAMIR).
AB  - BACKGROUND: Despite improved long-term safety of biodegradable polymer (BP) drug
      eluting stents (DES) compared to first-generation durable polymer (DP) DES, data
      on the safety and efficacy of BP-DES compared with second-generation (2G) DP-DES
      in patients with acute myocardial infarction (AMI) are limited. HYPOTHESIS: To
      evaluate the safety and efficacy of BP-DES compared with 2G-DP-DES in the higher
      stent thrombosis (ST) risk setting of AMI. METHODS: A total of 3359 AMI patients
      who received either BP-DES (n = 261) or 2G-DP-DES (n = 3098) were included from
      the Korea Acute Myocardial Infarction Registry (KAMIR). Differences in baseline
      clinical and angiographic characteristics were adjusted using a 1:5 propensity
      score matching analysis (n = 261 for BP-DES and n = 1305 for 2G-DP-DES). The
      primary outcome was the incidence of major adverse cardiac events (MACE)
      including all-cause death, recurrent myocardial infarction (re-MI), and target
      vessel revascularization (TVR). The rate of definite or probable ST was also
      investigated. RESULTS: In adjusted analysis, there was no significant difference
      between the 2 groups in baseline clinical and angiographic characteristics; 2
      year MACE (10.7% and 9.9% in the BP-DES group and 2G-DP-DES group, respectively,
      P = 0.679); ST incidence (0.8% vs 0.9%, respectively, P = 1.0), and rates of all
      cause death, re-MI, and TVR. By multivariate analysis, old age, diabetes
      mellitus, renal dysfunction, and left ventricular dysfunction were the
      independent predictors of MACE after BP-DES or 2G-DP-DES implantation.
      CONCLUSIONS: BP-DES and 2G-DP-DES appear to have comparable 2-year safety and
      efficacy for the treatment of AMI. However, longer-term follow-up is needed.

PMID- 27028304
TI  - Outcome of allogeneic transplantation in newly diagnosed and relapsed/refractory
      multiple myeloma: long-term follow-up in a single institution.
AB  - Allogeneic stem cell transplantation (allo-SCT) has the potential to induce long
      term remission in multiple myeloma (MM), but the role of allo-SCT in MM is
      controversial due to the high rate of treatment-related mortality (TRM). However,
      although proteasome inhibitors and immunomodulatory drugs have improved the
      outcome of patients with MM, high-risk patients still have a very poor prognosis.
      This indicates the need for new treatment strategies and identification of
      patients who might benefit from allo-SCT. We therefore analyzed the outcome of
      one hundred and forty-seven patients with MM who received an allo-SCT at our
      institution (58 in first line, 89 in relapsed/refractory setting) after a median
      follow-up of 88.8 months. For the first-line setting, median progression-free
      survival (PFS) and overall survival (OS) were remarkably good, with a CR rate of
      48.3%, median PFS of 30.2 months, and 10-yr OS of 51%. We found no difference in
      outcome for patients with high-risk metaphase cytogenetics or FISH del(13q14),
      but efficacy in current standard high-risk patients could not be determined. The
      outcome in the relapsed/refractory setting was poor, especially in the subgroup
      of patients relapsing within 18 months after auto-SCT. Therefore, if applied at
      all in these patients, improvement of allo-SCT is needed, focusing on reduction
      of TRM and more effective immunotherapy.

PMID- 27028305
TI  - High-level expression of periostin is significantly correlated with tumour
      angiogenesis and poor prognosis in osteosarcoma.
AB  - Periostin (PN), originally named as osteoblast-specific factor-2 (OSF-2), has
      been involved in regulating adhesion and differentiation of osteoblasts. Recently
      many studies have shown that high-level expression of PN is correlated
      significantly with tumour angiogenesis and prognosis in many kinds of human
      cancer. However, whether and how periostin expression influences prognosis in
      osteosarcoma remains unknown. This study aimed to examine the expression of PN in
      patients with osteosarcoma and explore the relationship of PN expression with
      clinicopathologic factors, tumour angiogenesis and prognosis.
      Immunohistochemistry was performed to determine the expression of PN in
      osteosarcoma and osteochondroma respectively. Vascular endothelial growth factor
      (VEGF) and CD34 were also examined in tissues from the osteosarcoma patients
      mentioned above. The results showed that PN expression was significantly (P <
      0.05) higher in osteosarcoma (80.9%) than in osteochondroma (14.7%). Increased PN
      protein expression was associated with histological subtype (P = 0.000), Enneking
      stage (P = 0.027) and tumour size (P = 0.009). The result also showed that high
      expression of PN correlated with VEGF expression (r = 0.285; P = 0.019) and that
      tumours with PN-positive expression significantly had higher microvessal density
      (44.6 +/- 13.7 vs. 20.6 +/- 6.5; P = 0.000) compared to those in normal bone
      tissues. Additionally, the expression of PN was found to be an independent
      prognostic factor in osteosarcoma patients. In conclusion, our findings suggest
      that PN may have an important role in tumour progression and may be used as a
      prognostic biomarker for patients with osteosarcoma.

PMID- 27028306
TI  - Potency and stability of compounded cyclophosphamide: a pilot study.
AB  - Compounding of drugs for use in veterinary oncology is becoming increasingly
      common. We obtained 15 mg cyclophosphamide capsules from five different
      compounding pharmacies and performed potency analyses at two time points, as well
      as stability at 60 days. Potency results for four out of five and zero out of
      five (4/10) samples analysed were inadequate. Stability at 60 days was acceptable
      for all but one sample. This pilot study raises several important points of
      concern when compounding chemotherapy in dogs and cats. Further studies are
      necessary to solidify this data. Collaboration between pharmacists, veterinarians
      and regulatory bodies is needed to ensure safe and accurate delivery of
      compounded drugs to client-owned animals.

PMID- 27028307
TI  - Donor variation effect on red blood cell storage lesion: a multivariable, yet
      consistent, story.
AB  - BACKGROUND: Previous studies have shown that baseline hematologic characteristics
      concerning or influencing red blood cell (RBC) properties might affect storage
      lesion development in individual donors. This study was conducted to evaluate
      whether variation in hemolysis, microparticle accumulation, phosphatidylserine
      (PS) exposure, and other storage lesion-associated variables might be a function
      of the prestorage hematologic and biologic profiles of the donor. STUDY DESIGN
      AND METHODS: Ten eligible, regular blood donors were paired and studied before
      donation (fresh blood) and during storage of RBCs in standard blood banking
      conditions. Plasma and cellular characteristics and modifications were evaluated
      by standard laboratory and biochemical or biologic analyses as well as by
      statistical and network analysis tools. RESULTS: Nitrate/nitrite and other
      bioactive factors exhibited high interdonor variability, which further increased
      during storage in a donor-specific manner. Storage lesion evaluators, including
      RBC fragility and PS exposure, fluctuated throughout the storage period in
      proportion to their values in fresh blood. Donors' levels of phosphatidylserine
      exposure and hemoglobin F correlated with stored cells' mean cell (RBC) Hb
      concentration, oxidative stress markers, and cellular fragility. DISCUSSION:
      Storage lesion indicators change in an orderly fashion, namely, by following
      donor-related prestorage attributes. These correlations are illustrated for the
      first time in "prestorage versus storage" biologic networks, which might help
      determine the best candidates for in vivo biomarkers of storage quality and
      provide deeper insight into the apparently complex donor variation effect on the
      RBC storage lesion.

PMID- 27028308
TI  - Understanding effects of topical ingredients on electrical measurement of skin
      hydration.
AB  - OBJECTIVE: Methods that assess skin hydration based on changes in its electrical
      properties are widely used in both cosmetic and medical research. However, the
      devices themselves often give results which are significantly different to each
      other. Although some work has previously been carried out to try and understand
      what these devices are actually reading, it was based on a technique for
      measuring the devices' responses to filter discs impregnated with different
      liquids, which could in itself be influencing the measurements. Presented here is
      a new method for measuring the devices' direct responses to different materials
      and solutions which removes any other confounding effects, thereby providing a
      clearer insight into their operation. METHODS: The responses of a variety of
      different liquids and solutions were measured using the Corneometer(r) and
      Skicon(r) . A new method is presented, based on the use of a custom-designed PTFE
      block to hold the liquids, allowing their measurement without using a filter
      paper. This method was developed and tested against the existing filter paper
      based approach. RESULTS: Differences were observed in results between filter
      paper- and PTFE block-based approach, indicating that the filter paper itself is
      capable of influencing the measurements and as such is not to be recommended for
      assessing how different liquids impact on results from the devices. A positive
      correlation was observed between Corneometer(r) and Skicon(r) readings for
      certain solutions and under certain conditions. A large influence of salt
      concentration was noted for the Skicon(r) device with no or minimal impact from
      the actual water itself, humectants and emollients. Salts, emollients, water and
      humectants were observed to have an effect on Corneometer(r) readings.
      CONCLUSIONS: Both the Corneometer(r) and Skicon(r) were influenced to different
      extents by chemicals other than water and therefore cannot be seen purely as
      measures of skin 'hydration'. Although there is strong evidence that the devices
      do correlate with expert assessment of skin dryness, the level of water in the
      skin is only part of the story when it comes to understanding the benefits of
      topical moisturizing products applied to the skin. An alternative approach would
      be to consider skin 'moisturization' as a property which is influenced by water,
      salts and other materials such as humectants and emollients, which is more
      consistent with how the stratum corneum itself helps to maintain its plasticity
      and flexibility. In the work presented here, the Corneometer(r) was more suited
      to providing a measurement which reflects the impact of multiple different
      components.

PMID- 27028309
TI  - Optical and Electrical Characteristics of Hybrid ZnO Nanowire/a-Si:H Solar Cells
      on Flexible Substrates under Mechanical Bending.
AB  - Disordered 3-D hybrid ZnO nanowire/a-Si:H thin-film radial-junction solar cells
      are directly fabricated onto flexible substrates. A 41% reduction in optical
      reflectivity resulted in a 15% increase in the current density when the substrate
      is mechanically bent concave-up toward the incoming light. The light scattering
      of the nanowire devices was enhanced by decreasing the spacing between the
      nanowire solar cell by bending the substrate.

PMID- 27028310
TI  - Effect of actionable somatic mutations on racial/ethnic disparities in head and
      neck cancer prognosis.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most
      common cancer worldwide and minorities have the worst survival. However, the
      molecular mechanisms underlying survival disparities have not been elucidated.
      METHODS: In a retrospective study, we assessed association between HNSCC early
      death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214
      patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African
      Americans (20%). RESULTS: Hispanic whites and African Americans had significantly
      higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was
      significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95%
      confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites
      (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR =
      3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor
      site, and tumor stage. CONCLUSION: We have provided the proof-of-principal data
      to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the
      way for precision medicine to overcome HNSCC survival disparities. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 38:1234-1241, 2016.

PMID- 27028311
TI  - Patterns of Chinese medicine use in prescriptions for treating Alzheimer's
      disease in Taiwan.
AB  - BACKGROUND: Certain Chinese medicine (CM) herbs and acupuncture may protect
      against Alzheimer's disease (AD). However, there is a lack of research regarding
      the use of CM in patients with AD. The aim of this study was to investigate CM
      usage patterns in patients with AD, and identify the Chinese herbal formulae most
      commonly used for AD. METHODS: This retrospective, nationwide, population-based
      cohort study was conducted using a randomly sampled cohort of one million
      patients, selected from the National Health Insurance Research Database between
      1997 and 2008 in Taiwan. CM use and the top ten most frequently prescribed
      formulae for treating AD were assessed, including average formulae dose and
      frequency of prescriptions. Demographic characteristics, including sex, age and
      insurance level were examined, together with geographic location. Existing
      medical conditions with the behavioral and psychological symptoms of dementia,
      and medications associated with CM were also examined. Factors associated with CM
      use were analyzed by multiple logistic regressions. RESULTS: The cohort included
      1137 newly diagnosed AD patients, who were given conventional treatment for AD
      between 1997 and 2008. Among them, 78.2 % also used CM treatments, including
      Chinese herbal remedies, acupuncture and massage manipulation. Female patients
      (aOR 1.57 with 95 % CI 1.16-2.13) and those living in urban areas (aOR 3.00 with
      95 % CI 1.83-4.90 in the middle of Taiwan) were more likely to use CM. After
      adjusting for demographic factors, AD patients suffering from the behavioral and
      psychological symptoms of dementia were more likely to seek CM treatment than
      those with no symptoms (aOR 2.26 with 95 % CI 1.48-3.43 in patients suffering
      more than three symptoms). Bu-Zhong-Yi-Qi-Tang and Ji-Sheng-Shen-Qi-Wan were the
      two formulae most frequently prescribed by CM practitioners for treating AD.
      CONCLUSION: Most people with AD who consumed herbal products used supplement qi,
      nourish the blood, and quiet the heart spirit therapy as complementary medicines
      to relieve AD-related symptoms, in addition to using standard anti-AD treatments.

PMID- 27028312
TI  - Presurgical Psychological Assessments as Correlates of Effectiveness of Spinal
      Cord Stimulation for Chronic Pain Reduction.
AB  - BACKGROUND: Spinal Cord Stimulator (SCS) is a surgically implanted device for
      patients with certain types of chronic pain. While some studies show the value of
      psychological screening of potential SCS candidates, no consensus exists. This
      single-site study analyzed the association of SCS success with psychological
      assessments (e.g., Millon Behavioral Medicine Diagnostic), beliefs regarding SCS
      efficacy, self-reported pain and quality of life (QOL) among patients approved
      for SCS. METHODS: Potential SCS candidates (N = 200) were contacted 3-7 years
      after initial psychological and medical clearance for SCS; 59 consented to a
      structured telephone interview. Thirty-four of the 59 had received a SCS; 25 had
      not received a SCS. Of the 34 that had received a SCS, 22 were approved by
      routine psychological evaluation while 12 went through in-depth psychological
      testing. RESULTS: The majority of respondents (62%) reported effective pain
      reduction, and 64% of SCS recipients reported improved QOL. Younger patients
      reported higher pre-implantation pain scores, and participants with higher levels
      of pain preimplantation were more likely say they would undergo the procedure
      again. Finally, persons reporting preoperative alcohol problems were more likely
      to report lower levels of post-SCS pain. CONCLUSION: Predictors of pain relief
      and QOL following SCS may depend on expectations of the device and on
      individuals' interpretation of pain or psychosocial health.

PMID- 27028313
TI  - Dual-Responsive Viscoelastic Lyotropic Liquid Crystal Fluids to Control the
      Diffusion of Hydrophilic and Hydrophobic Molecules.
AB  - A smart lyotropic liquid crystal (LLC) system was prepared to control the
      diffusion rate of hydrophilic and hydrophobic molecules. The LLC system is
      composed of a nonionic surfactant (tetraethylene glycol monododecylether; C12 EO4
      ) and an anionic azobenzene surfactant (Azo-surfactant). C12 EO4 was the main
      component of the LLC system. The Azo-surfactant, which can undergo photo
      isomerization, played the role of trigger in this system. LLC gels formed in a
      solution comprised of Azo-surfactant (10 mm) and C12 EO4 (300 mm). The LLC gels
      became broken when more Azo-surfactant was added (e.g., up to 15 mm) and the
      viscoelasticity was lost. Surprisingly, when we used UV light to irradiate the
      300 mm C12 EO4 /15 mm Azo-surfactant sample, the gel was recovered and high
      viscoelasticity was observed. However, under visible-light irradiation, the gel
      became broken again. The gel formation could also be triggered by heating the
      sample. On heating the 300 mm C12 EO4 /15 mm Azo-surfactant sample, the system
      thickened to a point at which typical gel behavior was registered. When the
      sample was cooled, the gel broke again. The LLC could be used for controlled
      release of hydrophilic and hydrophobic molecules, and could be considered as a
      versatile vehicle for the delivery of actives in systems of practical importance.

PMID- 27028314
TI  - Approach to Merosesquiterpenes via Lewis Acid Catalyzed Nazarov-Type Cyclization:
      Total Synthesis of Akaol A.
AB  - A Lewis acid catalyzed Nazarov-type cyclization of arylvinylcarbinol has been
      developed for the asymmetric synthesis of carbotetracyclic core of
      merosesquiterpenes. The reaction works only in the presence of 2 mol % of
      Sn(OTf)2 and Bi(OTf)3 in dichloroethane under elevated temperature. The
      methodology offers the synthesis of a variety of enantioenriched
      arylvinylcarbinols from commercially available (3aR)-sclareolide 9 in six steps
      with an eventual concise total synthesis of marine sesquiterpene quinol, akaol A
      (1a). 

PMID- 27028315
TI  - The impact of behavioural executive functioning and intelligence on math
      abilities in children with intellectual disabilities.
AB  - BACKGROUND: Little is known about the role of behavioural executive functioning
      (EF) skills and level of intelligence (IQ) on math abilities in children with
      mild to borderline intellectual disabilities. METHOD: Teachers of 63 children
      attending a school for special education (age: 10 to 13 years; IQ: 50 to 85)
      filled out a Behaviour Rating Inventory for Executive Function for each student.
      Furthermore, students took a standardised national composite math test and a
      specific math test on measurement and time problems. Information on level of
      intelligence was gathered through school records. Multiple regression analyses
      were performed to test direct, moderating and mediating effects of EF and IQ on
      math performance. RESULTS: Behavioural problems with working memory and
      flexibility had a direct negative effect on math outcome, while concurrently,
      level of intelligence had a positive effect. The effect of IQ on math skills was
      moderated by problems with inhibition: in children with a clinical level of
      inhibition problems, there was no effect of level of intelligence on math
      performance. CONCLUSIONS: Findings suggest that in students with mild to
      borderline intellectual disabilities and math difficulties, it is important to
      address their strengths and weaknesses with respect to EF and adjust instruction
      and remedial intervention accordingly.

PMID- 27028316
TI  - Efficacy of flurbiprofen 8.75 mg spray in patients with sore throat due to an
      upper respiratory tract infection: A randomised controlled trial.
AB  - BACKGROUND: Viral infections cause most cases of pharyngitis (sore throat);
      consequently, antibiotics are generally not warranted. However, a treatment
      targeting pain and inflammation, e.g. a topical non-steroidal anti-inflammatory
      spray, may be helpful for patients. OBJECTIVE: To evaluate the efficacy and
      safety of flurbiprofen 8.75 mg spray. METHODS: This randomised, double-blind,
      parallel group study was conducted at six community-based clinical research
      centres in Australia and two in New Zealand. Adults with sore throat due to upper
      respiratory tract infection (onset <= four days) took one dose of flurbiprofen (n
      = 249) or placebo spray (n = 256); after six hours, they could re-dose every
      three-six hours as required, for three days (max. five doses/day). The primary
      endpoint was the area under the change from baseline curve in throat soreness
      from zero-two hours (AUC0-2h). The change from baseline in other sore throat
      symptoms also assessed efficacy. RESULTS: The mean AUC0-2h for throat soreness
      was significantly greater with flurbiprofen spray (-1.82; 95% CI: -1.98 to 1.65)
      compared with placebo (-1.13; 95% CI: -1.27 to 0.99) (P < 0.0001). Significantly
      greater reductions from baseline were observed with flurbiprofen spray compared
      with placebo from the first time-points assessed (five minutes for throat
      soreness/difficulty swallowing, 20 minutes for sore throat pain intensity and 30
      minutes for swollen throat) for up to six hours (P < 0.05 for all). There was no
      significant difference in adverse events between treatment groups during the
      three-day study. CONCLUSION: Flurbiprofen spray provides rapid and long-lasting
      relief from sore throat symptoms, and is well-tolerated over three days.

PMID- 27028317
TI  - Role of ammonia, inflammation, and cerebral oxygenation in brain dysfunction of
      acute-on-chronic liver failure patients.
AB  - Hepatic encephalopathy (HE) is a common feature of acute-on-chronic liver failure
      (ACLF). Although ammonia, inflammation, and cerebral oxygenation are associated
      with HE in acute liver failure, their roles in ACLF are unknown. The aim of this
      prospective, longitudinal study was to determine the role of these
      pathophysiological variables in ACLF patients with and without HE. We studied 101
      patients with ACLF admitted to the intensive care unit. Severity of ACLF and HE,
      arterial ammonia, jugular venous oxygen saturation (JVO2 ), white blood cell
      count (WCC), and C-reactive protein were measured at days 0, 1, 3, and 7.
      Patients were followed until death or hospital discharge. Mortality was high (51
      patients, 50.5%), especially in patients with HE of whom 35 of 53 (66.0%) died
      regardless of ACLF severity. At baseline, increased WCC and abnormal JVO2 (high
      or low) were independent predictors of death. Further deterioration in
      inflammation, JVO2 , and ammonia were also predictive of mortality. JVO2
      deviation and hyperammonemia were associated with the presence and severity of
      HE; improvement in these parameters was associated with a reduction in HE grade.
      No direct interaction was observed between these variables in regards to
      mortality or HE. In conclusion, this study describes potential mechanisms of HE
      in ACLF indicating that ammonia and abnormal cerebral oxygenation are important.
      The results suggest that ammonia, JVO2 , and WCC are important prognostic
      biomarkers and therapeutic targets. The relative roles of these
      pathophysiological factors in the pathogenesis of HE in ACLF or guiding therapy
      to improve survival requires future study. Liver Transplantation 22 732-742 2016
      AASLD.

PMID- 27028318
TI  - Acquired reactive perforating collagenosis associated with systemic lupus
      erythematosus.

PMID- 27028319
TI  - HIV-infected CD4+ T Cells Use T-bet-dependent Pathway for Production of IL-10
      Upon Antigen Recognition.
AB  - Interleukin (IL)-10 has been implicated in persistence of pathogens in a number
      of chronic infections. Infected CD4+ cells upon reactivation with HIV antigens
      were also shown to produce IL-10, which might contribute to their persistence.
      Hence, it is crucial to determine mechanisms regulating IL-10 production after
      activation with HIV antigens for devising effective blocking strategies. In this
      study, ERK-, T-bet- and FoxP3-dependent pathways were evaluated for their
      possible roles in IL-10 production by infected CD4+ cells after reactivation with
      HIV Env. Intracellular and secreted IL-10 levels were determined by flow
      cytometry and Bioplex assay after treating PBMCs with PD98059, tipifarnib and
      cyclosporin A for blocking of ERK-, T-bet-and FoxP3-dependent pathways,
      respectively. Baseline levels of T-bet, pERK were higher in P24+ CD4+ cells as
      compared to uninfected CD4+ cells, which increased further after activation with
      Env. Inhibition of T-bet resulted in 2.3-fold reduction of IL-10 expression
      whereas ERK and FoxP3 inhibition failed to cause suppression of IL-10 expression.
      Conversely, IL-10 secreted by PBMCs was inhibited maximally after ERK inhibition
      suggesting its role in regulation of cytokine secretory pathway. IFN-gamma was
      found to be suppressed after treatment with inhibitors of all these pathways.
      Thus, the study highlighted need for IL-10 blockade along with the use of
      antigens for therapeutic vaccinations or latency reversal and identified the T
      bet-dependent pathway as an important pathway regulating IL-10 production by
      infected CD4+ cells. However, simultaneous blockade of IFN-gamma precludes use of
      inhibitor of this pathway as an IL-10 blocking strategy. 

PMID- 27028320
TI  - EVALUATION OF PAINFUL SHOULDER IN BASEBALL PLAYERS.
AB  - OBJECTIVE: To assess the relationship between shoulder mobility and strength and
      the presence of pain among baseball players. METHODS: Between April and July
      2009, 55 baseball players were assessed by the Shoulder and Elbow Group of the
      School of Medical Sciences, Santa Casa de Misericordia, Sao Paulo. They were all
      males, aged between 15 and 33 years (mean of 21); they attended an average of
      three training sessions per week and had been doing this sport for a mean of 10
      years. RESULTS: 14 of the 55 players evaluated were pitchers, and 20 reported
      pain during the pitching motion. The mean values for lateral and medial rotation
      and range of motion (ROM) in the dominant shoulder were, respectively, 110 
      degrees , 61  degrees  and 171  degrees , with a statistically significant
      difference in relation to the non-dominant limb. Pitchers had greater gains in
      lateral rotation and deficits in medial rotation than did non-pitchers. Pain
      presented a statistically significant correlation with diminished ROM, greater
      length of time playing the sport and situations of "shoulder at risk".
      CONCLUSIONS: Statistically significant differences in dominant shoulder mobility
      were found, with increased lateral rotation, diminished medial rotation and
      smaller ROM, in relation to the contralateral limb. There was a statistically
      significant relationship between the pitcher's position and greater gain in
      lateral rotation and diminished medial rotation. There were statistically
      significant correlations between pain and diminished ROM, greater length of time
      playing the sport and situations of "shoulder at risk". There was a statistical
      tendency suggesting that players with diminished medial rotation of the dominant
      shoulder presented a relationship with pain.

PMID- 27028323
TI  - Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in
      Border Areas of Western Cambodia.
AB  - Little is known about circulation of influenza and other respiratory viruses in
      remote populations along the Thai-Cambodia border in western Cambodia. We
      screened 586 outpatients (median age 5, range 1-77) presenting with influenza
      like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and
      December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was
      performed on combined nasal and throat specimens followed by viral culture,
      antigenic analysis, antiviral susceptibility testing and full genome sequencing
      for phylogenetic analysis. ILI-specimens negative for influenza were cultured,
      followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza
      was found in 168 cases (29%) and occurred almost exclusively in the rainy season
      from June to November. Isolated influenza strains had close antigenic and
      phylogenetic relationships, matching vaccine and circulating strains found
      elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western
      Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier
      Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9%
      genome conservation), despite sharing the majority of the amino acid changes with
      the Thai references. Most genes showed signatures of purifying selection. Viral
      culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non
      polio enteroviruses (10.3%) were detected among 164 culture-negative samples
      including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9
      using nested RT-PCR methods. A single specimen of EV71 was found. Despite
      proximity to Thailand, influenza epidemiology of these western Cambodian isolates
      followed patterns observed elsewhere in Cambodia, continuing to support current
      vaccine and treatment recommendations from the Cambodian National Influenza
      Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin
      genes, require further investigation in light of an increasingly important role
      of permissive mutations in influenza virus evolution. Further research about the
      burden of adenovirus and non-polio enteroviruses as etiologic agents in acute
      respiratory infections in Cambodia is also needed. 

PMID- 27028324
TI  - Unsupervised analysis reveals two molecular subgroups of serous ovarian cancer
      with distinct gene expression profiles and survival.
AB  - PURPOSE: Ovarian cancer is typically diagnosed at late stages, and thus,
      patients' prognosis is poor. Improvement in treatment outcomes depends, at least
      partly, on better understanding of ovarian cancer biology and finding new
      molecular markers and therapeutic targets. METHODS: An unsupervised method of
      data analysis, singular value decomposition, was applied to analyze microarray
      data from 101 ovarian cancer samples; then, selected genes were validated by
      quantitative PCR. RESULTS: We found that the major factor influencing gene
      expression in ovarian cancer was tumor histological type. The next major source
      of variability was traced to a set of genes mainly associated with extracellular
      matrix, cell motility, adhesion, and immunological response. Hierarchical
      clustering based on the expression of these genes revealed two clusters of
      ovarian cancers with different molecular profiles and distinct overall survival
      (OS). Patients with higher expression of these genes had shorter OS than those
      with lower expression. The two clusters did not derive from high- versus low
      grade serous carcinomas and were unrelated to histological (ovarian vs.
      fallopian) origin. Interestingly, there was considerable overlap between
      identified prognostic signature and a recently described invasion-associated
      signature related to stromal desmoplastic reaction. Several genes from this
      signature were validated by quantitative PCR; two of them-DSPG3 and LOX-were
      validated both in the initial and independent sets of samples and were
      significantly associated with OS and disease-free survival. CONCLUSIONS: We
      distinguished two molecular subgroups of serous ovarian cancers characterized by
      distinct OS. Among differentially expressed genes, some may potentially be used
      as prognostic markers. In our opinion, unsupervised methods of microarray data
      analysis are more effective than supervised methods in identifying intrinsic,
      biologically sound sources of variability. Moreover, as histological type of the
      tumor is the greatest source of variability in ovarian cancer and may interfere
      with analyses of other features, it seems reasonable to use histologically
      homogeneous groups of tumors in microarray experiments.

PMID- 27028325
TI  - Factors Associated with Infant Feeding Methods after the Nuclear Power Plant
      Accident in Fukushima: Data from the Pregnancy and Birth Survey for the Fiscal
      Year 2011 Fukushima Health Management Survey.
AB  - Objectives The objective of this study was to assess the frequency of and factors
      associated with infant feeding methods after the Fukushima nuclear power plant
      accident using data from the Fukushima Health Management Survey. Methods We
      conducted an anonymous self-administered questionnaire survey of 16,001 women who
      gave birth around the time of the Great East Japan Earthquake and registered
      their pregnancies at Fukushima Prefecture municipal offices between August 1,
      2010 and July 31, 2011. The responses of 8366 women were analyzed. Chi square
      tests and multiple logistic regression analysis were used to compare various
      factors between women who had formula-fed their children because of concern
      regarding radioactive contamination or other reasons and those who had breastfed
      exclusively. Results The percentage of women who had breastfed exclusively was
      30.9 %. The percentage of women who had both breastfed and formula-fed or formula
      fed exclusively was 69.1 %, of which 20.3 % formula-fed because of concern
      regarding radioactive contamination of breast milk. The use of formula feeding
      because of concern about radioactive contamination was significantly higher in
      women who had resided within the evacuation area and those whose regular
      antenatal care had been interrupted. The use of formula feeding for other reasons
      was significantly higher in women who had resided within the evacuation area and
      lower for those who had willingly switched to another medical institution.
      Conclusions for Practice Our results suggest the importance of providing
      breastfeeding support to women who are forced to evacuate or whose antenatal care
      is interrupted after a disaster.

PMID- 27028326
TI  - Investigation of Enthesopathy with Ultrasonography and Comparison with Skin
      Findings in Asymptomatic Psoriatic Patients.
AB  - BACKGROUND: Joint involvement associated with psoriasis is referred to as
      psoriatic arthritis. A late diagnosis of psoriatic arthritis may cause a variety
      of morbidities; therefore, an early diagnosis and treatment of psoriatic
      arthritis are required. Asymptomatic psoriatic arthritis has been found in 8-70%
      of patients with psoriasis using imaging techniques. OBJECTIVE: To investigate
      joint and enthesis regions by ultrasonography in patients with psoriasis without
      inflammatory joint symptoms to detect subclinical psoriatic arthritis. METHODS:
      We included 50 psoriasis patients and 30 healthy control subjects without joint
      complaint in this study. Twelve joint regions of all subjects in each group were
      examined by ultrasonography. RESULTS: The presence of any pathological
      ultrasonography finding (30%) was higher but did not significantly differ in
      psoriasis patients compared with the control group (13.33%; p > 0.05).
      CONCLUSION: Although statistically not significant, the pathological
      ultrasonography findings were approximately twofold more common in patients with
      psoriasis compared with the control group. Therefore, the development of
      psoriatic arthritis in patients with psoriasis should be more closely followed.

PMID- 27028327
TI  - Clostridium difficile Infection: A Model for Disruption of the Gut Microbiota
      Equilibrium.
AB  - The gut microbiota is a complex ecosystem defined by the combination of
      microorganisms living in the gastrointestinal tract. Its equilibrium is
      intimately involved in several aspects of vital process for human physiology and
      nutrition. Its composition changes depending on both exogenous and endogenous
      factors. The disruption of the gut microbiota by antibiotics often leads to an
      opportunistic infection by Clostridium difficile. The unbalanced intestinal
      microbiota promotes spore germination, growth of vegetative forms and toxin
      production leading to C. difficile infection, which is characterized by diarrhea
      and possibly pseudomembranous colitis. This nosocomial infection is a good model
      to understand the role of the gut microbiota in preventing the development of
      pathogens. 

PMID- 27028329
TI  - Motor and Nonmotor Features of Carriers of the p.A53T Alpha-Synuclein Mutation: A
      Longitudinal Study.
AB  - BACKGROUND: G209A SNCA mutation carriers represent an important group of genetic
      PD. We describe motor and nonmotor features of G209A SNCA mutation carriers.
      METHODS: Longitudinal clinical assessments over 2 years were collected in 22
      symptomatic and 8 asymptomatic G209A SNCA mutation carriers. Motor and nonmotor
      rating scales were administered. Correlations were performed between clinical
      variables and disease duration or age. Penetrance was calculated using Kaplan
      Meier survival curves. RESULTS: Asymptomatic carriers did not manifest clear
      premotor symptoms, but symptomatic carriers often reported that olfactory
      dysfunction and rapid eye movement sleep behavior disorder preceded motor
      symptoms. Prominent motor decline and deterioration of autonomic and cognitive
      function occurred at follow-up; such nonmotor features correlated with disease
      duration, but not age. Disease penetrance was estimated at around 90%.
      CONCLUSIONS: This study may help to inform clinical trials and provide the basis
      for studies of disease modifiers in genetic synucleinopathy cohorts. (c) 2016
      International Parkinson and Movement Disorder Society.

PMID- 27028330
TI  - Nitrous oxide production during nitrification from organic solid waste under
      temperature and oxygen conditions.
AB  - Landfill aeration can accelerate the biological degradation of organic waste and
      reduce methane production; however, it induces nitrous oxide (N2O), a potent
      greenhouse gas. Nitrification is one of the pathways of N2O generation as a by
      product during aerobic condition. This study was initiated to demonstrate the
      features of N2O production rate from organic solid waste during nitrification
      under three different temperatures (20 degrees C, 30 degrees C, and 40 degrees C)
      and three oxygen concentrations (5%, 10%, and 20%) with high moisture content and
      high substrates' concentration. The experiment was carried out by batch
      experiment using Erlenmeyer flasks incubated in a shaking water bath for 72 h. A
      duplicate experiment was carried out in parallel, with addition of 100 Pa of
      acetylene as a nitrification inhibitor, to investigate nitrifiers' contribution
      to N2O production. The production rate of N2O ranged between 0.40 * 10(-3) and
      1.14 * 10(-3) mg N/g-DM/h under the experimental conditions of this study. The
      rate of N2O production at 40 degrees C was higher than at 20 degrees C and 30
      degrees C. Nitrification was found to be the dominant pathway of N2O production.
      It was evaluated that optimization of O2 content is one of the crucial parameters
      in N2O production that may help to minimize greenhouse gas emissions and N
      turnover during aeration. 

PMID- 27028331
TI  - Computed tomography assessment for transcatheter mitral valve interventions.
AB  - Multidetector cardiac computerized tomography (CT) is a robust advanced imaging
      modality with high spatial resolution that has emerged as an essential tool for
      the planning of structural heart and electrophysiology interventions. The most
      notable example has been its important role in the pre-procedural planning of
      transcatheter aortic valve replacement (TAVR), which has developed to the point
      that commercial software packages are commonly used for this application. More
      recently several novel approaches and devices have been developed for
      transcatheter mitral valve replacement (TMVR). Given the greater complexity of
      mitral valve anatomy, CT has at least an equally important role for preprocedural
      planning of TMVR. Similar to TAVR assessment, its utility in TMVR is multi-fold,
      including assessment of valve and adjacent anatomical structures, determination
      of accurate annulus dimensions for prosthesis sizing, vascular access planning,
      and prediction of fluoroscopic angles. 

PMID- 27028332
TI  - Defining the clinical need and indications: who are the right patients for
      transcatheter mitral valve replacement.
AB  - Mitral regurgitation (MR) can be divided into two major etiologies, primary and
      secondary MR. Primary MR, also termed degenerative or organic MR, is a disease of
      the valve itself and is treated routinely by surgical repair in all but
      prohibitive risk patients. In these patients, transcatheter repair techniques,
      including edge to edge repair with the MitraClip device have been largely
      successful and widely adopted. Transcatheter placement of artificial chords has
      also been performed. The potential role for transcatheter mitral valve
      replacement (TMVR) in primary MR will likely be quite limited. Secondary or
      functional MR is due to a disease of the left ventricle and not the valve itself.
      The MR is a result of dilation of the left ventricle causing distraction of the
      papillary muscles with tethering of the mitral leaflets and lack of leaflet
      coaptation. Medical therapy is the mainstay treatment, with resynchronization
      used in appropriate patients. Surgical repair, usually with an undersized
      annuloplasty, is used in a limited number of patients. Transcatheter edge to edge
      repair is used extensively outside the US in secondary MR and is the subject of a
      pivotal trial in the US. However, it is in this group of patients with secondary
      MR that there is the largest clinical unmet need and, hence, the greatest
      potential opportunity for TMVR. At least ten TMVR platforms are in early
      feasibility, first in human, or preclinical trial stages. Four devices have
      cumulative early human experience in <100 patients. In this article, we discuss
      those patients most likely to benefit from TMVR and detail lessons learned from
      the first human studies regarding patient selection. 

PMID- 27028333
TI  - Anatomical challenges for transcatheter mitral valve intervention.
AB  - Following the success of transcatheter aortic and pulmonary valve implantation,
      there is a large interest in transcatheter mitral valve interventions to treat
      severe mitral regurgitation (MR). With the exception for the MitraClipTM (Abbott,
      Abbott Park, IL, USA) edge-to-edge leaflet plication system, most of these
      transcatheter mitral valve interventions are still in their early clinical or
      preclinical development phase. Challenges arising from the complex anatomy of the
      mitral valve and the interplay of the mitral apparatus with the left ventricle
      (LV) have contributed to a more difficult development process and mixed clinical
      results with these novel technologies. This review aims to discuss the several
      anatomical aspects and challenges related to transcatheter mitral valve
      intervention--the relevant anatomy will be reviewed in relation to specific
      requirements for device design and procedural aspects of transcatheter mitral
      valve interventions. To date, experience with these novel therapeutic modalities
      are still limited and resolution of many challenges are pending. Future studies
      have to evaluate for whom the transcatheter approach is a feasible and preferred
      treatment and which patients will benefit from either transcatheter mitral valve
      repair or replacement. Nevertheless, technological developments are anticipated
      to drive the transcatheter approach forward into a clinically feasible
      alternative to surgery for selected patients with severe MR.

PMID- 27028334
TI  - PBAC score: an easy-to-use tool to predict coagulation disorders in women with
      idiopathic heavy menstrual bleeding.

PMID- 27028335
TI  - Stranded: causes and effects of discharge delays involving non-acute in-patients
      requiring maintenance care in a tertiary hospital general medicine service.
AB  - Objectives The aims of the present study were to identify causes of prolonged
      discharge delays among non-acute in-patients admitted to a tertiary general
      medicine service, quantify occupied bed days (OBDs) and propose strategies for
      eliminating avoidable delays. Methods A retrospective study was performed of
      patients admitted between 1 January 2012 and 31 May 2015 and discharged as non
      acute cases requiring maintenance care and who incurred a total non-acute length
      of stay (LOS) >7 days and total hospital LOS >14 days. Long-stay patients with
      non-acute LOS >=28 days were subject to chart review in ascertaining serial
      causes of discharge delay and their attributable OBDs. Literature reviews and
      staff feedback identified potential strategies for minimising delays. Results Of
      the 406 patients included in the present study, 131 incurred long-stays; for
      these 131 patients, delays were identified that accounted for 5420 of 6033 (90%)
      non-acute OBDs. Lack of available residential care beds was most frequent,
      accounting for 44% of OBDs. Waits for outcomes of guardianship applications
      accounted for 13%, whereas guardian appointments, Public Trustee applications and
      funding decisions for equipment or care packages each consumed between 4% and 5%
      of OBDs. Family and/or carer refusal of care accounted for 7%. Waits for aged
      care assessment team (ACAT) assessments, social worker reports, geriatrician or
      psychiatrist reviews and confirmation of enduring power of attorney each
      accounted for between 1% and 3% of OBDs. Of 30 proposed remedial strategies,
      those rated as high priority were: greater access to interim care or respite care
      beds or supported accommodation, especially for patients with special needs;
      dedicated agency officers for hospital guardianship applications and greater
      interagency collaboration and harmonisation of assessment and decision processes;
      and formal requests from hospital administrators to patients and family to accept
      care options and attend mediation meetings. Conclusions Delayed discharge of non
      acute maintenance care patients results principally from impaired access to
      residential care, administrative delays involving external agencies and patient
      or family refusal of care. Proposed remedial actions require concerted
      interjurisdictional advocacy. What is known about this topic? Delays in discharge
      of non-acute patients requiring maintenance care can occur for many reasons and
      incur inordinately long hospital stays. What does this paper add? The present
      detailed chart review of 131 long-stay non-acute patients identified causes of
      serial discharge delays and quantified their prevalence and attributable bed
      days. Waits for residential care accounted for less than half the bed days,
      administrative delays involving decisions by agencies external to the hospital
      accounted for one-quarter and patient or family refusal of care options accounted
      for one-tenth. Strategies are proposed that may minimise these delays. What are
      the implications for practitioners? Delayed discharge of non-acute patients
      requiring maintenance care threatens to consume an ever-increasing proportion of
      acute hospital bed days. Remedial action is required from stakeholders both
      within and outside hospitals to reverse this trend.

PMID- 27028336
TI  - Should the century-old practice of psychotherapy defer to science and ignore its
      foundations in two millennia of ethical thought?
AB  - While agreeing with the mainstream view that psychotherapeutic practice must be
      grounded in science, including research on the effectiveness of psychotherapy,
      the author advocates giving more weight to the venerable philosophical literature
      on ethics that bears directly on what patients bring to therapists: problems in
      living. These problems have been the domain of ethics since Socrates, who--like
      psychotherapists--promoted reflective dialogue. This article reviews some
      contemporary thought regarding the importance of reflection and the limits that
      patients and therapists face in promoting it. Relying on attachment theory and
      the process of mentalizing, the author identifies a convergence of science and
      ethics in the therapeutic aspiration to cultivate epistemic trust and illustrates
      this convergence with a case example.

PMID- 27028337
TI  - Improving medication adherence for severely mentally ill adults by decreasing
      coercion and increasing cooperation.
AB  - Severe mental illnesses, mainly schizophrenia and bipolar disorders, often go
      untreated until the afflicted persons become dangerous to themselves or others.
      In such states, they must be hospitalized and medicated, often involuntarily due
      to the stigma and low insight into need for treatment that can be considered
      characteristic of severe illnesses. Hospitalization and medications can help the
      mentally ill stabilize. But these options also can have a demoralizing effect on
      future engagement with providers. Accordingly, the process of involuntary
      hospitalization and medication treatment must be maximally dignified and
      respectful of patient autonomy, within the limits of manifest illnesses.
      Literature that was reviewed and synthesized suggests best practice strategies
      for helping involuntary mentally ill patients grow into voluntary consumers of
      medication. In turn, risk of relapse is lowered and quality of life is enhanced.
      Best practice strategies included decreasing usage of coercive tactics, helping
      patients cope with medication side effects, and emphasizing the necessity of
      family involvement. The authors conclude with a review of the limitations of
      arguing for involuntary hospitalization and treatment as restoring patient
      autonomy, along with implications for future practice focusing on increasing the
      medication adherence of severely mentally ill populations. 

PMID- 27028338
TI  - Effectivenes of a track-based model for treating eating disorders in a general
      psychiatric hospital.
AB  - Due to comorbid disorders or the degree of severity of their eating disorder,
      individuals may not warrant treatment at a specialty eating disorder facility.
      This article examines the effectiveness of a track-based model for treating
      eating disorders at a general inpatient psychiatric hospital. One hundred seventy
      six patients who participated on the Eating Disorder Track and completed the
      Eating Disorder Inventory-3 (EDI; Garner, 2004) were examined to determine
      whether their eating disorder symptoms improved over the course of their
      treatment. Results indicated that patients significantly improved across all
      eating disorder risk scales and psychological scales measured by the Eating
      Disorder Inventory. This suggests that patients who may not meet the criteria for
      attending a specialty eating disorder program may receive an alternative form of
      treatment for their eating disorder that is effective in reducing their eating
      disorder symptomatology. The hope is that providing more treatment options will
      expand the reach of eating disorder treatments to more individuals who need
      specialized care for these disorders. 

PMID- 27028339
TI  - Fact or fiction? A longitudinal study of play and the development of reflective
      functioning.
AB  - In Fonagy and Target's (1996, 2000) developmental model of mentalization, play is
      theorized as a precursor of later mentalization and reflective function (RF);
      however, the relationship between play and later mentalization and RF has yet to
      be empirically tested. These processes are particularly important in the context
      of trauma, but an empirical model of the relationships among mentalization, play,
      and trauma is currently lacking. The aim of this longitudinal study was to
      examine whether children's capacity to engage in pretend play, to symbolize, and
      to make play narratives was associated with later RF in those children. Thirty
      nine sexually abused children and 21 nonabused children (aged 3 to 8)
      participated in the study. The Children's Play Therapy Instrument was used to
      assess children's free play. Three years after the play assessment, children's RF
      was assessed using the Child Attachment Interview, coded with the Child and
      Adolescent Reflective Functioning Scale. Pretend play completion was associated
      with later other-understanding. Play was also found to mediate the relationship
      between sexual abuse and children's later mentalization regarding others. These
      findings are consistent with Fonagy and Target's emphasis on the role of pretend
      play in the development of a nuanced sense of the qualities of the mind and
      reality. In sum, the findings lend support to Fonagy and Target's account of
      playing with reality, and the development of mentalization suggests that it may
      be more than "fiction." Furthermore, these results suggest that children's
      ability to create meaningful and coherent play sequences after sexual abuse is
      associated with the development of a better understanding of their relationships
      with others. Clinical implications and future directions are discussed. 

PMID- 27028340
TI  - Postdischarge suicide: A psychodynamic understanding of subjective experience and
      its importance in suicide prevention.
AB  - Recent discharge from a psychiatric inpatient facility is associated with a high
      risk of suicide. There are multiple factors that may contribute to this increase
      in risk. Psychodynamic considerations about the patient's subjective experience
      of suicidality, hospitalization, and discharge are often overlooked but are
      critical to understanding this phenomenon. Qualitative research has begun to
      provide empirical support for the importance of the psychological aspects of
      discharge, and the heightened state of vulnerability that patients experience
      during this time. Review of the literature and careful consideration of clinical
      experience is helpful in elucidating this experience in a way that can inform
      effective treatment. This article integrates a psychodynamic understanding of
      suicidality in the postdischarge period with a review of empirical research and
      formulates clinical recommendations for suicide prevention. 

PMID- 27028341
TI  - Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol
      Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary
      Syndrome.
AB  - BACKGROUND: Insulin resistance in women with polycystic ovary syndrome (PCOS) may
      be mediated, in part, by a deficiency in the insulin-stimulated release of a d
      chiro-inositol-inositolphosphoglycan (DCI-IPG) mediator of insulin action.
      Supporting this idea, several studies have reported improved insulin sensitivity
      in both lean and obese women with PCOS after oral administration of DCI.
      Pioglitazone improves insulin sensitivity in women with PCOS, but it is unknown
      whether this may be contributed by enhanced insulin-stimulated release of the DCI
      IPG second messenger. The study aimed to determine if pioglitazone increases
      release of biologically active DCI-IPG per unit insulin released during an oral
      glucose tolerance test (OGTT). METHODS: A randomized, double-blind placebo
      controlled trial was conducted in 32 women with PCOS at a tertiary referral
      center in Venezuela. The intervention comprised administration of pioglitazone 45
      mg daily or matched placebo for 6 months. Outcome measures included area under
      curves (AUC) of DCI-IPG (AUCDCI-IPG), insulin (AUCinsulin), and the ratio of
      AUCDCI-IPG to AUCinsulin during a 2-hr OGTT. RESULTS: After treatment with
      pioglitazone, AUCinsulin during the OGTT decreased and whole body insulin
      sensitivity, as determined by the Matsuda index, increased significantly only in
      the pioglitazone group. The ratio of AUCDCI-IPG/AUCinsulin increased in the
      pioglitazone group by 1.85-fold (P < 0.0001) with no significant change in the
      placebo group. Change in Matsuda index correlated with change in DCI-IPG released
      per unit of insulin during OGTT (r = 0.47, P < 0.01). CONCLUSION: In women with
      PCOS, pioglitazone increased insulin-stimulated release of the DCI-IPG second
      messenger of insulin action, which may contribute to its insulin-sensitizing
      effect in these women.

PMID- 27028342
TI  - Evaluation of the mirn23a Cluster through an iTRAQ-based Quantitative Proteomic
      Approach.
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that
      are implicated in a number of disease states. MiRNAs can exist as individual
      entities or may be clustered and transcribed as a single polycistron. The mirn23a
      cluster consists of three miRNAs: miR-23a, miR-24-2, and miR-27a. Although these
      miRNAs are transcribed together, they often exist at varying levels in the cell.
      Despite the fact that the mirn23a cluster is known to play a role in a number of
      diseases and developmental processes, few direct targets have been identified. In
      this study, we examined the effects of miR-23a, miR-24-2, miR-27a, or the mirn23a
      cluster overexpression on the proteome of 70Z/3 pre-B lymphoblast cells.
      Quantitative mass spectrometry using isobaric tags for relative and absolute
      quantification (iTRAQ) allowed for the global profiling of cell lines after miRNA
      overexpression. We identified a number of targets of each miRNA that contained
      predicted miRNA seed sequences and are likely direct targets. In addition, we
      discovered a cohort of shared miRNA targets and cluster targets, demonstrating
      the importance of studying miRNA clusters in their entirety.

PMID- 27028344
TI  - Oesophageal narrowing on barium oesophagram is more common in adult patients with
      eosinophilic oesophagitis than PPI-responsive oesophageal eosinophilia.
AB  - BACKGROUND: To date there have been no clear features that aid in differentiating
      patients with eosinophilic oesophagitis (EoE) from PPI-responsive oesophageal
      eosinophilia (PPI-REE). However, barium swallow roentgenography is a more
      sensitive and specific measure to detect subtle fibrostenotic remodeling changes
      present in EoE. We aim to characterise any clinical, endoscopic, histiological or
      barium roentgenographic differences between EoE and PPI-REE. AIM: To characterise
      any clinical, endoscopic, histiological or barium roentgenographic differences
      between EoE and PPI-REE. METHODS: We performed a retrospective cohort analysis on
      data collected from a tertiary referral centre population from 2010 to 2015. Data
      from 66 patients with EoE and 28 patients with PPI-REE were analysed. Cases were
      adults who met consensus guidelines for EOE, and had a barium swallow study
      within 6 months of the index endoscopy. Clinical, endoscopic, histiological and
      barium swallow findings were collected. RESULTS: Patients with EoE reported
      similar characteristics as PPI-REE patients, except EoE patients were younger
      (35.6 vs. 46.6 years; P = 0.011), had earlier symptom onset (29.0 vs. 38.0 years;
      P = 0.026), and smaller oesophageal diameters on barium swallow (19.5 mm vs. 20;
      P = 0.042). Patients with EoE were more likely to have distal strictures (EoE 77%
      vs. 25%; P = 0.02) and, importantly, a greater likelihood of small calibre
      oesophagus (51.5% vs. 17.9%; P = 0.002). Moreover, EoE patients had a higher
      probability of developing small calibre oesophagus after 20 years of symptoms
      (72.3% vs. 30.2%; P = 0.074) compared to PPI-REE patients. CONCLUSIONS: When
      compared with eosinophilic oesophagitis, PPI-REE patients demonstrate findings
      that suggest PPI-responsive oesophageal eosinophilia to be a later onset, less
      aggressive form of oesophageal stricturing disease than eosinophilic
      oesophagitis.

PMID- 27028343
TI  - Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with type I
      diabetes mellitus.
AB  - INTRODUCTION: Patients with type I diabetes mellitus (T1DM) have increased
      incidence of atherosclerosis and cardiovascular disease. Although these
      complications are unusual in children with T1DM, prevention, and early
      intervention could decrease morbidity and mortality. Osteoprotegerin (OPG),
      asymmetric dimethylarginine (ADMA), and Fetuin-A have been associated with
      increased cardiovascular risk (CVR). Increased OPG and ADMA, and decreased or
      increased Fetuin-A serum levels have been associated with increased CVR. AIM:
      Because patients with T1DM have higher CVR we investigated OPG, ADMA, and Fetuin
      A, in children with T1DM. METHODS: We determined the serum levels of OPG,
      receptor activator of nuclear factor-kappaB ligand (RANKL), ADMA, and Fetuin-A by
      enzyme-linked immunosorbent assay (ELISA) in 56 children with T1DM aged 12.1 +/-
      3.4 yr and in 46 normal control children, (C) aged 11.3 +/- 3.0 yr. RESULTS:
      Serum OPG levels were significantly increased in patients with T1DM (3.352 +/-
      0.73 pmol/L) compared with C (2.75 +/- 0.67 pmol/L, p < 0.0001) but RANKL did not
      change. ADMA was significantly decreased in T1DM compared with C (0.68 +/- 0.13
      umol/L versus 0.82 +/- 0.18 umol/L, p < 0.0001). Fetuin-A was similar in T1DM
      (0.551 +/- 0.13 g/L) and C (0.540 +/- 0.11 g/L) subjects. OPG was positively
      associated with glycosylated hemoglobin A1c (p < 0.001) and negatively associated
      with BMI (p < 0.01). ADMA and Fetuin-A were not associated with A1c and ADMA was
      only negatively associated with age (p < 0.05). CONCLUSION: OPG is increased,
      ADMA is decreased, but RANKL and Fetuin-A are unchanged in T1DM children. Whereas
      increased OPG has been firmly related to increased CVR, more studies, especially
      longitudinal studies, are needed to delineate the role and clinical significance
      of decreased ADMA and if Fetuin-A has any role in T1DM.

PMID- 27028345
TI  - A case-control study of hopelessness and suicidal behavior in the city of Athens,
      Greece. The role of the financial crisis.
AB  - This study aimed to examine the psychometric properties of Beck Hopelessness
      Scale (BHS) in Greek patients with a recent suicide attempt, the predictive
      ability of BHS especially in terms of age and the possible effect of the
      financial crisis on hopelessness as it has been identified as a significant
      suicide risk factor. The study included a total of 510 individuals, citizens of
      Athens, Greece. Three hundred and forty individuals (170 attempted suicide
      patients, and 170 -age and gender- matched healthy individuals used as controls)
      completed BHS before the financial crisis onset (from 2009 to 2010). A sample of
      170 healthy individuals also completed the BHS after the financial crisis onset
      (from 2013 to 2014), when the impact of the austerity measures was being felt by
      the Greek society. The Greek BHS version demonstrated good psychometric
      properties and a sufficient degree of internal consistency. Attempted suicide
      patients (M = 9) presented higher hopelessness than the controls (M = 3). The
      patients' age positively correlated with hopelessness (rs = .35, p < .001), and
      the ROC curve revealed that the BHS ability to discriminate the individuals with
      pathological rates of hopelessness from those without, strengthened as age
      increased. No significant differences were found between the individuals
      evaluated before (M = 3) and after (M = 3, p > .05) the crisis onset.
      Nevertheless, regarding the latter group, the women, the younger individuals, the
      less educated, the unemployed and the participants with low or mediocre self
      reported financial status presented increased hopelessness. Our findings suggest
      that BHS could be a useful instrument especially when screening for suicide risk
      in people of older age, and that the financial crisis in Greece had a greater
      impact on subgroups of the population regarding hopelessness.

PMID- 27028346
TI  - Sprint running: how changes in step frequency affect running mechanics and leg
      spring behaviour at maximal speed.
AB  - The purpose of this study was to investigate the changes in selected
      biomechanical variables in 80-m maximal sprint runs while imposing changes in
      step frequency (SF) and to investigate if these adaptations differ based on
      gender and training level. A total of 40 athletes (10 elite men and 10 women, 10
      intermediate men and 10 women) participated in this study; they were requested to
      perform 5 trials at maximal running speed (RS): at the self-selected frequency
      (SFs) and at SF +/-15% and +/-30%SFs. Contact time (CT) and flight time (FT) as
      well as step length (SL) decreased with increasing SF, while kvert increased with
      it. At SFs, kleg was the lowest (a 20% decrease at +/-30%SFs), while RS was the
      largest (a 12% decrease at +/-30%SFs). Only small changes (1.5%) in maximal
      vertical force (Fmax) were observed as a function of SF, but maximum leg spring
      compression (DeltaL) was largest at SFs and decreased by about 25% at +/-30%SFs.
      Significant differences in Fmax, Deltay, kleg and kvert were observed as a
      function of skill and gender (P < 0.001). Our results indicate that RS is
      optimised at SFs and that, while kvert follows the changes in SF, kleg is lowest
      at SFs.

PMID- 27028347
TI  - RETRACTED: Carotenoids, Mycosporine-Like Amino Acid Compounds, Phycobiliproteins,
      And Scytonemin In The Genus Scytonema (Cyanobacteria): A Chemosystematic Study1.
AB  - The following article from the Journal of Phycology, "Carotenoids, Mycosporine
      Like Amino Acid Compounds, Phycobiliproteins, And Scytonemin In The Genus
      Scytonema (Cyanobacteria): A Chemosystematic Study," submitted by Antonia D.
      Asencio, and published online on August 22, 2011 on Wiley Online Library
      (http://www.wileyonlinelibrary.com), has been retracted by agreement between the
      journal Editor, Robert Sheath, and Wiley Periodicals, Inc. The retraction has
      been agreed upon request by Ferran Garcia-Pichel, listed as co-author, but not
      having agreed to the submission or publication of the manuscript.

PMID- 27028348
TI  - No correlation between statin exposure and incident diabetes mellitus in HIV-1
      infected patients receiving combination antiretroviral therapy.
AB  - OBJECTIVES: Recent clinical studies and one meta-analysis have shown a modest but
      significant increase in the incidence of diabetes mellitus associated with statin
      exposure, so this correlation was investigated in a cohort of HIV-positive
      subjects. METHODS: A retrospective cohort study including adult HIV-1-infected
      patients followed at our Clinic of Infectious Diseases between 2007 and 2014 was
      performed. RESULTS: We assessed 3170 HIV-positive patients with a median follow
      up of 5.2 years. The incidence of diabetes mellitus was 1.2 per 100 person-years
      and it was not significantly associated with the prescription of statins [hazard
      ratio (HR) 1.09 per year of statin exposure; 95% confidence interval (CI) 0.7
      1.49; P = 0.067], while it was associated with older age, chronic hepatitis C,
      antiretroviral-naive vs. antiretroviral experienced condition, high body mass
      index, and high serum concentration of triglycerides. CONCLUSIONS: In our study,
      a higher risk of diabetes mellitus was not associated with statin treatment, but
      with some traditional risk factors.

PMID- 27028349
TI  - Adjuvant Pelvic Radiation Therapy+/-Vaginal Brachytherapy in Patients With High
      risk Stage I or Stage II Uterine Papillary Serous, Clear Cell, and High-grade
      Endometrioid Carcinoma.
AB  - PURPOSE: Radiation therapy (RT) for stages I-II uterine papillary serous
      carcinoma (UPSC), clear cell (CC), and high-grade endometrioid (HGE) carcinoma
      present a treatment challenge. Regimens include external beam radiotherapy (EBRT)
      with or without brachytherapy. We examine the use of these radiation modalities
      in these endometrial cancers (EC) with respect to cause-specific survival (CSS).
      METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was
      queried for patients with AJCC stages I-II UPSC, CC, or HGE cancer treated with
      hysterectomy and RT between 1998 and 2008. Patients who did not receive adjuvant
      RT or received brachytherapy alone were excluded. CSS was evaluated by the Kaplan
      Meier survival analysis and the log-rank test was used to compare CSS.
      Multivariate analysis was performed using the Cox proportional hazards regression
      model. Adjusted hazard ratios (HR) were calculated for risk of EC death. RESULTS:
      There were 1653 patients included in this analysis. The overall 100-month CSS for
      the entire cohort was 81.0%. The 100-month CSS was 85.3% for EBRT alone and 86.5%
      for EBRT+brachytherapy (P=0.72). Stage IC/IIA/IIB patients had a greater risk of
      EC death compared with stage IA/IB patients (adjusted HR=2.39; P<0.0001).
      Patients with UPSC and CC had a slightly higher risk of EC death compared with
      HGE (adjusted HR=1.01 [P=0.97] and 1.42 [P=0.02], respectively). On subset
      analysis, there was no difference in CSS with the addition of brachytherapy for
      UPSC (P=0.37), CC (P=0.27), or HGE cancer patients (P=0.42). Patients treated
      with brachytherapy in addition to EBRT did not demonstrate a reduced adjusted
      risk of EC death compared with EBRT alone (P=0.38). CONCLUSIONS: The addition of
      brachytherapy to adjuvant EBRT in stages I-II UPSC, CC, and HGE cancer did not
      demonstrate superior CSS. Thus, patients may not benefit from the addition of
      brachytherapy to EBRT.

PMID- 27028350
TI  - Oncologic and Functional Hazards of Obesity Among Patients With Locally Advanced
      Rectal Cancer Following Neoadjuvant Chemoradiation Therapy.
AB  - OBJECTIVE: Obesity is a major health concern and risk factor for colorectal
      cancer that may also impact cancer treatment and outcomes. Rectal cancer response
      to chemoradiotherapy (CXRT) is associated with long-term survival and sphincter
      preservation. The purpose of this study was to evaluate the impact of obesity on
      treatment outcomes after neoadjuvant CXRT for rectal cancer. METHODS: A
      retrospective cohort study of patients diagnosed (1993 to 2010) with cT3-4 or cN+
      (by endorectal ultrasound, computed tomography, or magnetic resonance imaging)
      rectal carcinoma and treated with CXRT and total mesorectal excision was
      performed. Patients were classified as obese (body mass index >=30 kg/m) or
      nonobese (body mass index <30 kg/m), and by response to CXRT: complete (pCR) or
      incomplete (pIR). Associations between obesity, tumor response, and sphincter
      preservation were evaluated using multivariate logistic regression analysis and
      survival outcomes by Cox regression. RESULTS: A total of 753 patients met
      criteria and 28.7% (n=216) patients were obese. Obese and nonobese groups did not
      differ in age, sex, tumor location, grade, or number of examined lymph nodes.
      However, obesity was associated with a lower rate of pCR (ORmulti=0.60; 95%
      confidence interval, 0.38-0.94; P=0.04) and among mid to low rectal cancer
      patients, a lower rate of sphincter preservation (ORmulti=0.67; 95% confidence
      interval, 0.45-0.99). Among both obese and nonobese patients, CR was associated
      with more favorable recurrence-free survival than pIR. CONCLUSIONS: Considering
      the increasing obesity prevalence and its association with CXRT response,
      oncologic outcomes, and sphincter preservation, further study is needed regarding
      the impact of obesity on neoadjuvant treatment response. Moreover, obesity should
      be targeted as a modifiable risk factor for adverse outcomes following
      multimodality treatment for rectal cancer.

PMID- 27028351
TI  - Use of Metabolic Parameters as Prognostic Factors During Concomitant
      Chemoradiotherapy for Locally Advanced Cervical Cancer.
AB  - OBJECTIVES: To investigate the use of metabolic parameters as early prognostic
      factors during concomitant chemoradiotherapy for locally advanced cervix
      carcinoma (LACC). MATERIALS AND METHODS: Between February 2008 and January 2012,
      34 consecutive patients treated for LACC (International Federation of Gynecology
      and Obstetrics Staging System stage IB2-IVA) were included in a retrospective
      study. Treatment was standard of care: total dose of 45 Gy in 1.8 Gy per fraction
      with concurrent cisplatin followed by brachytherapy. 18F-FDG PET-CT modalities
      were performed before treatment and per-treatment (at 40 Gy). The analyzed
      parameters were: maximum standardized uptake value (SUVmax), SUVmax variations of
      the primary tumor between the 2 investigations (DSUVmax), metabolic tumor volume
      (MTV), and total lesion glycolysis (TLG). Survival was assessed according to
      early metabolic changes during chemoradiotherapy. RESULTS: Median follow-up was
      16 months (range, 5.3 to 32.4 mo). Median SUVmax before treatment was 13.15 (5.9
      to 31) and was 5.05 (0 to 12) per-treatment. Median DSUVmax was 63.97% (0% to
      100%). Median MTV before treatment was 44.16 mL (3.392 to 252.768 mL) and was
      5.44 mL (0 to 69.88 mL) per-treatment. Median TLG before treatment was 249.82 mL
      (13.40 to 1931.10 mL) and was 20.14 mL (0 to 349.99 mL) per-treatment. At 40 Gy,
      SUVmax>=6, DSUVmax<=40%, MTV>=5.6 mL, and TLG>=21.6 mL were significantly
      associated with overall survival and progression-free survival reduction. MTV
      predicted progression with a sensitivity of 80% and a specificity of 87.5% and
      TLG with a sensitivity of 80% and a specificity of 83.3%. CONCLUSIONS: PET-CT
      imaging could be useful as an early prognostic factor during treatment for LACC.
      MTV and TLG seem to provide better prognostic information than SUVmax and
      DSUVmax.

PMID- 27028352
TI  - Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities
      of novel derivatives from harmine.
AB  - We synthesized two series of new hydrazide harmine derivatives. The reaction of
      harmine 1 with ethyl acetate chloride afforded the corresponding ethyl ester 2.
      The treatment of 2 with hydrazine hydrate gave the hydrazide 3 which further
      converted into hydrazones 4a-j and dihydrazides 5a-c. A series of new triazoles
      7a-f has also been prepared from the suitable propargyl harmine 6. The
      synthesized derivatives were characterized by 1H-NMR, 13C-NMR, and HRMS and
      evaluated for their activities against MCF7, HCT116 OVCAR-3, acetylcholinesterase
      and 5-lipoxygenase. The most hydrazones derivatives 4a-j have a good cytotoxic
      activity against all cell lines, when 4a, 4d, 4f and 4 g are more active than 1
      (against OVCAR-3 IC50 16.7-2.5 MUM). The compound 6 was the most active (IC50 =
      1.9 MUM) against acetylcholinesterase. Some compounds exhibited significant
      activity against 5-lipoxygenase (IC50 = 30.9-63.1 MUM).

PMID- 27028353
TI  - Syntactic and semantic processing of Chinese middle sentences: evidence from
      event-related potentials.
AB  - Scalp-recorded event-related potentials are known to be sensitive to particular
      aspects of sentence processing. The N400 component is widely recognized as an
      effect closely related to lexical-semantic processing. The absence of an N400
      effect in participants performing tasks in Indo-European languages has been
      considered evidence that failed syntactic category processing appears to block
      lexical-semantic integration and that syntactic structure building is a
      prerequisite of semantic analysis. An event-related potential experiment was
      designed to investigate whether such syntactic primacy can be considered to apply
      equally to Chinese sentence processing. Besides correct middles, sentences with
      either single semantic or single syntactic violation as well as double syntactic
      and semantic anomaly were used in the present research. Results showed that both
      purely semantic and combined violation induced a broad negativity in the time
      window 300-500 ms, indicating the independence of lexical-semantic integration.
      These findings provided solid evidence that lexical-semantic parsing plays a
      crucial role in Chinese sentence comprehension.

PMID- 27028355
TI  - On the influence of re-reading on mind wandering.
AB  - Re-reading has been shown to have a minimal benefit on text comprehension, in
      comparison to reading only once or other types of study techniques (e.g.,
      testing; self-explanation). In two experiments we examined the effect of re
      reading on mind wandering. Participants read two texts, during which they
      responded to intermittent mind wandering probes. One text was read once and the
      other twice. Consistent with previous findings, there was no effect of re-reading
      on comprehension even though participants reported feeling more competent when
      they re-read the text. Critically, participants mind wandered more while re
      reading. Furthermore, the effect of re-reading on mind wandering was specific to
      intentional forms of mind wandering rather than unintentional. The implications
      of these results for understanding mind wandering and the limited effectiveness
      of re-reading as a mnemonic are discussed.

PMID- 27028354
TI  - Detailed functional and structural phenotype of Bietti crystalline dystrophy
      associated with mutations in CYP4V2 complicated by choroidal neovascularization.
AB  - PURPOSE: To describe in detail the phenotype of a patient with Bietti crystalline
      dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the
      response to intravitreal Bevacizumab (Avastin(r); Genentech/Roche). METHODS: A 34
      year-old woman with BCD and mutations in CYP4V2 (c.802
      8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full
      field flash electroretinography (ERG), kinetic and two-color dark-adapted
      perimetry, and dark-adaptometry. Imaging was performed with spectral domain
      optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength
      (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). RESULTS:
      Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left
      eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic
      fields were normal in the peripheral extent. Retinal crystals were most obvious
      on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD
      OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod
      > cone sensitivity loss surrounded fixation and extended to ~10 degrees  of
      eccentricity corresponding to regions of photoreceptor outer segment-retinal
      pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer
      was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin
      bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co
      localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of
      CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of
      BCVA to baseline (20/25). CONCLUSION: crystals in BCD were predominantly located
      within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie
      the relatively extensive retinal dysfunction observed in relatively early-stage
      BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.

PMID- 27028356
TI  - Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural
      Stem Cells.
AB  - Direct-write printing of stem cells within biomaterials presents an opportunity
      to engineer tissue for in vitro modeling and regenerative medicine. Here, a first
      example of constructing neural tissue by printing human neural stem cells that
      are differentiated in situ to functional neurons and supporting neuroglia is
      reported. The supporting biomaterial incorporates a novel clinically relevant
      polysaccharide-based bioink comprising alginate, carboxymethyl-chitosan, and
      agarose. The printed bioink rapidly gels by stable cross-linking to form a porous
      3D scaffold encapsulating stem cells for in situ expansion and differentiation.
      Differentiated neurons form synaptic contacts, establish networks, are
      spontaneously active, show a bicuculline-induced increased calcium response, and
      are predominantly gamma-aminobutyric acid expressing. The 3D tissues will
      facilitate investigation of human neural development, function, and disease, and
      may be adaptable for engineering other 3D tissues from different stem cell types.

PMID- 27028357
TI  - Eruptive Reddish-Yellow Coalescing Papules in the Axillae of a Middle-Aged Man.

PMID- 27028359
TI  - Shake-up effect in photoluminescence of integer quantum Hall system formed in
      InGaAs/InP quantum wells.
AB  - Polarization-resolved magneto-photoluminescence is studied in InGaAs/InP single
      quantum wells. In the range of the filling factor nu >= 4 the number of populated
      Landau levels contributing to the photoluminescence is found to be equal to the
      corresponding filling factor, while at nu <= 3 the number of emitting Landau
      levels is larger than the filling factor, which implies an occupancy of the
      Landau levels above the Fermi level. Such partial occupancy of the Landau levels
      with energies higher than the Fermi energy is due to shake-up processes caused by
      electron-electron interaction. In accordance to the theory, at the filling factor
      around nu = 2 the shake-up process was found to manifest itself in the
      downshifted cusp of the energy of the sigma- polarized emission from the excited
      Landau levels, while no change was observed in the energy of the sigma+ polarized
      emission. The different energies of differently spin-polarized excited Landau
      levels cause the magnetic field induced polarization of the emission from excited
      Landau levels. In addition, the bound electron-hole excitonic complexes (trions)
      associated with different Landau levels were observed.

PMID- 27028358
TI  - Novel mechanisms power bacterial gliding motility.
AB  - For many bacteria, motility is essential for survival, growth, virulence, biofilm
      formation and intra/interspecies interactions. Since natural environments differ,
      bacteria have evolved remarkable motility systems to adapt, including swimming in
      aqueous media, and swarming, twitching and gliding on solid and semi-solid
      surfaces. Although tremendous advances have been achieved in understanding
      swimming and swarming motilities powered by flagella, and twitching motility
      powered by Type IV pili, little is known about gliding motility. Bacterial
      gliders are a heterogeneous group containing diverse bacteria that utilize
      surface motilities that do not depend on traditional flagella or pili, but are
      powered by mechanisms that are less well understood. Recently, advances in our
      understanding of the molecular machineries for several gliding bacteria revealed
      the roles of modified ion channels, secretion systems and unique machinery for
      surface movements. These novel mechanisms provide rich source materials for
      studying the function and evolution of complex microbial nanomachines. In this
      review, we summarize recent findings made on the gliding mechanisms of the
      myxobacteria, flavobacteria and mycoplasmas.

PMID- 27028360
TI  - Comparison of hospital length of stay and hospitalization costs among patients
      with non-valvular atrial fibrillation treated with apixaban or warfarin: An early
      view.
AB  - OBJECTIVE: To quantify and compare hospital length of stay (LOS) and costs
      between hospitalized non-valvular atrial fibrillation (NVAF) patients treated
      with either apixaban or warfarin via a large claims database. METHODS: Adult
      patients hospitalized with AF were selected from the Premier Perspective Claims
      Database (01JAN2013-31MARCH2014). Patients with evidence of valvular heart
      disease, valve replacement procedures, or pregnancy during the index
      hospitalization were excluded. Patients treated with apixaban or warfarin during
      hospitalization were identified. Propensity score matching (PSM) was performed to
      control for baseline imbalances between patients treated with apixaban or
      warfarin. Primary outcomes were hospital LOS (days), post-medication
      administration LOS, and index hospitalization costs, and were compared using
      paired t-tests in the matched sample. RESULTS: Before PSM, 2894 apixaban and
      124,174 warfarin patients were identified. Patients treated with warfarin were
      older and sicker compared to those treated with apixaban. After applying PSM, a
      total of 2886 patients were included in each cohort, and baseline characteristics
      were balanced. The mean (standard deviation [SD] and median) hospital LOS was
      significantly (p = 0.002) shorter for patients treated with apixaban for 5.1 days
      (5.7 and 3) compared to warfarin for 5.5 days (4.8 and 4). The trend appeared
      consistent in the hospital LOS from point of apixaban or warfarin administration
      to discharge (4.5 vs 4.7 days, p = 0.051). Patients administered apixaban
      incurred significantly lower hospitalization costs compared to those administered
      warfarin ($11,262 vs $12,883; p < 0.001). CONCLUSIONS: Among NVAF patients,
      apixaban treatment was associated with significantly shorter hospital LOS and
      lower costs when compared to warfarin treatment.

PMID- 27028361
TI  - Dermatological aspects of synthetic cannabinoid addiction.
AB  - CONTEXT: Synthetic cannabinoids (SCs) have recently become one of the most abused
      substances among young population and have caused severe health consequences in
      our country and worldwide. OBJECTIVE: The aim of this study was to investigate
      sociodemographic and dermatological findings in SC addicts. MATERIALS AND
      METHODS: A total of 136 SC users who applied to our hospital's Substance
      Dependence Center outpatient clinic and diagnosed with drug addiction according
      to DSM-4 criteria between September 2014 and September 2015 were enrolled to our
      study. Patients were evaluated by dermatologist and psychiatrist with
      sociodemographic and clinical data sheets. Data were obtained by direct
      conversation with patients, clinical examination findings, and laboratory tests,
      if necessary. RESULTS: Of 136 patients, 12 (8.8%) were female and 124 (91.2%)
      were male, aged between 17 and 53 with mean age of 25.8 +/- 9.2. Most common use
      way of SC was smoking and patients majorly used opiates before SC. The majority
      of the patients enrolled to our study were low-educated and almost 50% did not
      have a regular job. The most frequent dermatologic complaints were periorbital
      darkening, hallowed-cheeks and premature aging, hair loss and gray hair, and
      acnes, whereas most frequent dermatologic examination findings were artifact
      lesions such as blade scars and tobacco scars-stains, tattoos, and acnes.
      DISCUSSION AND CONCLUSIONS: Given the increased prevalence of SC use in our
      country and around the world, dermatologists should continue to familiarize
      themselves with the common mucocutaneous markers of this substance use. Awareness
      of signs of SCs use will facilitate earlier diagnose, intervention, and directed
      treatment.

PMID- 27028362
TI  - Performance of CT Angiography on a Mobile Stroke Treatment Unit: Implications for
      Triage.
AB  - BACKGROUND: There is a strong inverse relationship between outcome in patients
      with acute ischemic stroke from emergent large vessel occlusion (ELVO), and time
      to reperfusion from intra-arterial therapy. Delay in transferring patients to
      thrombectomy-capable centers is currently a major limitation. The mobile stroke
      unit (MSU) concept with onboard portable computed tomography (CT) scanner enables
      rapid performance of CT angiography (CTA) of the intracranial vessels to detect
      ELVO in the field, and allows for rapid triage of patients to interventional
      capable centers. METHODS: Our institution implemented a mobile stroke treatment
      unit (MSTU) program that started on July 2014, and CTA capability was added on
      April 2015. The eligibility criteria, equipment, and method of CTA imaging are
      described. We report the first case of CTA being performed in the field in the
      United States to aid in triage of ELVO patients. RESULTS: MSTU was dispatched for
      reported new onset of right hemiparesis in a patient. Teleneurological assessment
      detected findings consistent with a severe left middle cerebral artery (MCA)
      syndrome. Noncontrast CT head revealed left lenticulostriate hypoattenuation. A
      CTA was performed subsequently on the MSTU that showed an MCA cutoff. Based on
      these findings, patient was immediately transferred to the main hospital with
      neurointerventional capability, where he underwent successful recanalization with
      improvement in symptoms. CONCLUSION: CTA is possible on an MSTU, enabling rapid
      detection and triage of ELVO cases directly to thrombectomy-capable centers,
      which significantly reduces time to endovascular treatment.

PMID- 27028363
TI  - Phosphonate-Derived Nanoporous Metal Phosphates and Their Superior Energy Storage
      Application.
AB  - Nanoporous nickel, aluminum, and zirconium phosphates (hereafter, abbreviated as
      NiP, AlP, and ZrP, respectively) with high surface areas and controlled
      morphology and crystallinity have been synthesized through simple calcination of
      the corresponding phosphonates. For the preparation of phosphonate materials,
      nitrilotris(methylene)triphosphonic acid (NMPA) is used as phosphorus source. The
      organic component in the phosphonate materials is thermally removed to form
      nanoporous structures in the final phosphate materials. The formation mechanism
      of nanoporous structures, as well as the effect of applied calcination
      temperatures on the morphology and crystallinity of the final phosphate
      materials, is carefully discussed. Especially, nanoporous NiP materials have a
      spherical morphology with a high surface area and can have great applicability as
      an electrode material for supercapacitors. It has been found that there is a
      critical effect of particle sizes, surface areas, and the crystallinities of NiP
      materials toward electrochemical behavior. Our nanoporous NiP material has
      superior specific capacitance, as compared to various phosphate nanomaterials
      reported previously. Excellent retention capacity of 97% is realized even after
      1000 cycles, which can be ascribed to its high structural stability. 

PMID- 27028364
TI  - Predicting the Onset of Alcohol Use and the Development of Alcohol Use Disorder
      Among Indigenous Adolescents.
AB  - Empirical efforts to identify the predictors of drinking behavior among North
      American Indigenous adolescents are relatively limited. Using longitudinal data,
      this study considers perceived discrimination, positive drinker prototypes, and
      peer drinking behavior as risk factors for the onset of alcohol use and
      development of an alcohol use disorder among 674 Indigenous adolescents as they
      progressed from early to late adolescence (M age at baseline = 11.11, SD = 0.83).
      Results showed that positive drinker prototypes and associations with peers who
      drink increased the risk for the onset of drinking, while perceived
      discrimination and associations with peers who drink increased the risk for the
      development of an alcohol use disorder. The theoretical and practical
      implications of our results are discussed.

PMID- 27028365
TI  - Crystal Structure of an Ammonia-Permeable Aquaporin.
AB  - Aquaporins of the TIP subfamily (Tonoplast Intrinsic Proteins) have been
      suggested to facilitate permeation of water and ammonia across the vacuolar
      membrane of plants, allowing the vacuole to efficiently sequester ammonium ions
      and counteract cytosolic fluctuations of ammonia. Here, we report the structure
      determined at 1.18 A resolution from twinned crystals of Arabidopsis thaliana
      aquaporin AtTIP2;1 and confirm water and ammonia permeability of the purified
      protein reconstituted in proteoliposomes as further substantiated by molecular
      dynamics simulations. The structure of AtTIP2;1 reveals an extended selectivity
      filter with the conserved arginine of the filter adopting a unique unpredicted
      position. The relatively wide pore and the polar nature of the selectivity filter
      clarify the ammonia permeability. By mutational studies, we show that the
      identified determinants in the extended selectivity filter region are sufficient
      to convert a strictly water-specific human aquaporin into an AtTIP2;1-like
      ammonia channel. A flexible histidine and a novel water-filled side pore are
      speculated to deprotonate ammonium ions, thereby possibly increasing permeation
      of ammonia. The molecular understanding of how aquaporins facilitate ammonia flux
      across membranes could potentially be used to modulate ammonia losses over the
      plasma membrane to the atmosphere, e.g., during photorespiration, and thereby to
      modify the nitrogen use efficiency of plants. 

PMID- 27028366
TI  - Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and
      molecular aspects.
AB  - Apert and Crouzon are the most common craniosynostosis syndromes associated with
      mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a
      study to examine the molecular biology, brain abnormalities, and cognitive
      development of individuals with these syndromes. A retrospective longitudinal
      review of 14 patients with Apert and Crouzon syndromes seen at the outpatient
      Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in
      Brazil from January 1999 through August 2010 was performed. Patients between 11
      and 36 years of age (mean 18.29 +/- 5.80), received cognitive evaluations,
      cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients
      with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that
      ranged from 47 to 108 (mean 76.9 +/- 20.2), and structural brain abnormalities
      were identified in five of eight patients. Six patients presented with a gain-of
      function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from
      47 to78 (mean 67.2 +/- 10.7). One patient with a gain-of-function mutation
      (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice
      mutation (940-2A ->G) had a FSIQ of 104. Six patients with Crouzon syndrome had
      with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to
      102 (mean 93.5 +/- 6.7). These reveal that molecular aspects are another factor
      that can be considered in studies of global and cognitive development of patients
      with Apert and Crouzon syndrome (CS). (c) 2016 Wiley Periodicals, Inc.

PMID- 27028367
TI  - Psychotic symptoms and smoking in 44 countries.
AB  - OBJECTIVE: To assess the association between psychotic symptoms and smoking among
      community-dwelling adults in 44 countries. METHOD: Data from the World Health
      Survey (WHS) for 192 474 adults aged >=18 years collected in 2002-2004 were
      analyzed. The Composite International Diagnostic Interview was used to identify
      four types of past 12-month psychotic symptoms. Smoking referred to current daily
      and non-daily smoking. Heavy smoking was defined as smoking >=30 tobacco
      products/day. RESULTS: The pooled age-sex-adjusted OR (95% CI) of psychotic
      symptoms (i.e., at least one psychotic symptom) for smoking was 1.35 (1.27-1.43).
      After adjustment for potential confounders, compared to those with no psychotic
      symptoms, the ORs (95% CIs) for smoking for 1, 2, and >=3 psychotic symptoms were
      1.20 (1.08-1.32), 1.25 (1.08-1.45), and 1.36 (1.13-1.64) respectively. Among
      daily smokers, psychotic symptoms were associated with heavy smoking (OR = 1.45,
      95% CI = 1.10-1.92), and individuals who initiated daily smoking at <=15 years of
      age were 1.22 (95% CI = 1.05-1.42) times more likely to have psychotic symptoms.
      CONCLUSIONS: An increased awareness that psychotic symptoms are associated with
      smoking is important from a public health and clinical point of view. Future
      studies that investigate the underlying link between psychotic symptoms and
      smoking prospectively are warranted.

PMID- 27028368
TI  - Zinc delays the progression of obesity-related glomerulopathy in mice via down
      regulating P38 MAPK-mediated inflammation.
AB  - OBJECTIVE: Obesity, particularly child obesity, is one of the most common public
      health problems in the world and raises the risk of end-stage renal disease. Zinc
      (Zn) is essential for multiple organs in terms of normal structure and function;
      however, effects of Zn deficiency or supplementation among young individuals with
      obesity have not been well studied. METHODS: Weaned mice were fed high-fat diets
      (HFD) with varied contents of Zn (Zn deficient, adequate, and supplemented) for 3
      or 6 months. This study examined associations between renal pathogenesis and
      dietary Zn levels, specifically assessing inflammatory pathways by utilizing P38
      MAPK inhibitor SB203580. RESULTS: HFD feeding induced typical syndromes of
      obesity-related renal disorders, which worsened by Zn marginal deficiency. The
      progression of obesity-related renal disorders was delayed by Zn supplementation.
      HFD induced renal inflammation, reflected by increased P38 MAPK phosphorylation
      along with increases of inflammatory cytokines MCP-1, IL-1beta, IL-6, and TNF
      alpha. P38 MAPK inhibition prevented renal pathological changes in mice fed with
      HFD and HFD/Zn deficiency. CONCLUSIONS: P38 MAPK mediated the renal inflammatory
      responses, which played a central role in the pathogenesis of HFD-induced renal
      disorders. Zn could delay the progression of obesity-related kidney disease by
      down-regulating P38 MAPK-mediated inflammation.

PMID- 27028369
TI  - Autonomic response during bladder hydrodistention reflects the severity of
      symptoms in patients with bladder pain syndrome/interstitial cystitis.
AB  - AIMS: To evaluate the correlation between symptom severity of bladder pain
      syndrome/interstitial cystitis (BPS/IC) and autonomic nervous system activity, we
      examined autonomic responses during bladder hydrodistention. METHODS: Medical
      records were collected from a prospective database for patients who underwent
      bladder hydrodistention with a fixed protocol from March 2012 to December 2013. A
      total of 40 patients (16 males, 24 females) were included for the analysis.
      Hydrodistention was performed under general anesthesia (31 patients), spinal
      anesthesia (six patients), and both types of anesthesia (three patients) at
      different times. Twenty-five patients who underwent holmium laser enucleation of
      the prostate served as controls. Pulse rate (PR), systolic (SBP), and diastolic
      blood pressure (BP) were measured pre-hydrodistention, during hydrodistention,
      and after drainage. RESULTS: The spinal anesthesia and control groups exhibited
      little change in BP and PR during hydrodistention, while a significant increase
      was demonstrated in the general anesthesia group (e.g., DeltaSBP 4.89 +/- 4.80,
      10.40 +/- 19.03, and 56.26 +/- 30.38 mm Hg, respectively, P < 0.001). Under
      general anesthesia, autonomic response during hydrodistention was more prominent
      in patients with preoperative visual analogue scale (VAS) pain score >=7,
      Hunner's lesion, and glomerulation grade 4. Preoperative maximal cystometric
      capacity negatively correlated with changes in SBP during hydrodistention (R2  =
      0.294, P = 0.009), while VAS score and interstitial cystitis problem index
      demonstrated a positive correlation with the changes (R2  = 0.208, P = 0.012; R2 
      = 0.173, P = 0.015). CONCLUSIONS: Under general anesthesia, exaggerated autonomic
      responses to bladder hydrodistention were demonstrated in BPS/IC patients, which
      reflected the severity of symptoms. These results support the hypothesis of
      altered activity of autonomic system in BPS/IC. Neurourol. Urodynam. 36:677-682,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028371
TI  - Comparison of the type and severity of early attentional network decline after
      total intravenous or epidural anesthesia in middle-aged women after gynecological
      surgery.
AB  - Compared with regional anesthesia, general anesthesia may increase the risk of
      postoperative cognitive decline. This study aimed to investigate the type and
      severity of attentional network decline and the recovery of attentional networks
      in middle-aged women after gynecological surgery. A total of 140 consenting women
      undergoing elective gynecological surgery were enrolled in the study. Patients
      were assigned randomly to receive either total intravenous anesthesia or epidural
      anesthesia. To determine the efficacy of the attentional networks, patients were
      examined for alerting, orienting, and executive networks on the preoperative day
      and on the first and fifth postoperative days using the attentional network test.
      Significant differences were observed in the effect scores of the three
      attentional networks at all time points. These effect scores differed
      significantly between groups and between 1 and 5 days postoperation (DPO).
      Participants showed significantly lower effect scores for the alerting and
      orienting network tasks and had more difficulties in resolving conflict at 1 DPO
      compared with the baseline. On comparing effect scores between baseline and 5
      DPO, no significant differences on the alerting and orienting network tasks were
      observed in the epidural anesthesia group, a significant difference on the
      orienting network task was observed in the general anesthesia group, and
      significant differences on the executive control network were observed in both
      the groups. Compared with epidural anesthesia, total intravenous anesthesia is
      more likely to impair and delay the recovery of attentional networks in middle
      aged women undergoing elective hysterectomy. The executive control function
      showed marked damage and there were difficulties in recovery from either type of
      anesthesia.

PMID- 27028370
TI  - When Lowest Dose for Shortest Amount of Time Does Not Apply.

PMID- 27028372
TI  - Papular acantholytic dyskeratosis of the vulva associated with familial Hailey
      Hailey disease.
AB  - Papular acantholytic dyskeratosis (PAD) of the vulva is a rare, chronic disorder
      first described in 1984. It presents in young women as white to skin-coloured
      smooth papules over the vulva, which are persistent but asymptomatic.
      Histologically, there is hyperkeratosis and focal parakeratosis with acantholytic
      and dyskeratotic cells forming corps ronds and grains, placing PAD within
      Ackerman's spectrum of focal acantholytic dyskeratoses with Hailey-Hailey disease
      (HHD) and Darier disease. There have been 17 previous reports of PAD of the
      vulva, to our knowledge. Only one demonstrated a familial pattern, and none of
      the cases was associated with a family history of HHD. This is the first report
      of PAD and HHD in a single family, suggesting that PAD and HHD lie on a spectrum
      of disease and are genetically linked. 

PMID- 27028373
TI  - Progress in Corneal Stromal Repair: From Tissue Grafts and Biomaterials to
      Modular Supramolecular Tissue-Like Assemblies.
AB  - Corneal injuries and degenerative conditions have major socioeconomic
      consequences, given that in most cases, they result in blindness. In the quest of
      the ideal therapy, tissue grafts, biomaterials, and modular engineering
      approaches are under intense investigation. Herein, advancements and shortfalls
      are reviewed and future perspectives for these therapeutic strategies discussed. 

PMID- 27028374
TI  - The red edge excitation shift phenomenon can be used to unmask protein structural
      ensembles: implications for NEMO-ubiquitin interactions.
AB  - To understand complex molecular interactions, it is necessary to account for
      molecular flexibility and the available equilibrium of conformational states.
      Only a small number of experimental approaches can access such information.
      Potentially steady-state red edge excitation shift (REES) spectroscopy can act as
      a qualitative metric of changes to the protein free energy landscape (FEL) and
      the equilibrium of conformational states. First, we validate this hypothesis
      using a single Trp-containing protein, NF-kappaB essential modulator (NEMO). We
      provide detailed evidence from chemical denaturation studies, macromolecular
      crowding studies, and the first report of the pressure dependence of the REES
      effect. Combination of these data demonstrate that the REES effect can report on
      the 'ruggedness' of the FEL and we present a phenomenological model, based on
      realistic physical interpretations, for fitting steady-state REES data to allow
      quantification of this aspect of the REES effect. We test the conceptual
      framework we have developed by correlating findings from NEMO ligand-binding
      studies with the REES data in a range of NEMO-ligand binary complexes. Our
      findings shed light on the nature of the interaction between NEMO and poly
      ubiquitin, suggesting that NEMO is differentially regulated by poly-ubiquitin
      chain length and that this regulation occurs via a modulation of the available
      equilibrium of conformational states, rather than gross structural change. This
      study therefore demonstrates the potential of REES as a powerful tool for
      tackling contemporary issues in structural biology and biophysics and elucidates
      novel information on the structure-function relationship of NEMO and key
      interaction partners.

PMID- 27028375
TI  - History of Retractor Technologies for Percutaneous Pedicle Screw Fixation
      Systems.
AB  - Minimally invasive techniques aimed at minimizing surgery-associated risk and
      morbidity of spinal surgery have increased in popularity in recent years. Their
      potential advantages include reduced length of hospital stay, blood loss, and
      requirement for post-operative analgesia and earlier return to work. One such
      minimally invasive technique is the use of percutaneous pedicle screw fixation,
      which is paramount for promoting rigid and stable constructs and fusion in the
      context of trauma, tumors, deformity and degenerative disease. Percutaneous
      pedicle screw insertion can be an intimidating prospect for surgeons who have
      only been trained in open techniques. One of the ongoing challenges of this
      percutaneous system is to provide the surgeon with adequate access to the pedicle
      entry anatomy and adequate tactile or visual feedback concerning the position and
      anatomy of the rod and set-screw construct. This review article discusses the
      history and evolution of percutaneous pedicle screw retractor technologies and
      outlines the advances over the last decade in the rapidly expanding field of
      minimal access surgery for posterior pedicle screw based spinal stabilization. As
      indications for percutaneous pedicle screw techniques expand, the nuances of the
      minimally invasive surgery techniques and associated technologies will also
      multiply. It is important that experienced surgeons have access to tools that can
      improve access with a greater degree of ease, simplicity and safety. We here
      discuss the technical challenges of percutaneous pedicle screw retractor
      technologies and a variety of systems with a focus on the pros and cons of
      various retractor systems. 

PMID- 27028376
TI  - Construction Strategy and Progress of Whole Intervertebral Disc Tissue
      Engineering.
AB  - Degenerative disc disease (DDD) is the major cause of low back pain, which
      usually leads to work absenteeism, medical visits and hospitalization. Because
      the current conservative procedures and surgical approaches to treatment of DDD
      only aim to relieve the symptoms of disease but not to regenerate the diseased
      disc, their long-term efficiency is limited. With the rapid developments in
      medical science, tissue engineering techniques have progressed markedly in recent
      years, providing a novel regenerative strategy for managing intervertebral disc
      disease. However, there are as yet no ideal methods for constructing tissue
      engineered intervertebral discs. This paper reviews published reports pertaining
      to intervertebral disc tissue engineering and summarizes data concerning the seed
      cells and scaffold materials for tissue-engineered intervertebral discs,
      construction of tissue-engineered whole intervertebral discs, relevant animal
      experiments and effects of mechanics on the construction of tissue-engineered
      intervertebral disc and outlines the existing problems and future directions.
      Although the perfect regenerative strategy for treating DDD has not yet been
      developed, great progress has been achieved in the construction of tissue
      engineered intervertebral discs. It is believed that ongoing research on
      intervertebral disc tissue engineering will result in revolutionary progress in
      the treatment of DDD. 

PMID- 27028377
TI  - Titanium/Polyetheretherketone Cages for Cervical Arthrodesis with Degenerative
      and Traumatic Pathologies: Early Clinical Outcomes and Fusion Rates.
AB  - OBJECTIVE: Anterior cervical discectomy and fusion is the most commonly employed
      surgical technique for treating cervical spondylosis. Although autologous bone
      grafts are considered the gold standard in achieving fusion, associated short-
      and long-term morbidities have led to a search for alternative materials. These
      have included carbon-fiber, titanium alloy (Ti) and ceramic and
      polyetheretherketone (PEEK) based implants. Recent attempts to optimize cage
      implants through using composite designs have combined Ti and PEEK. However,
      there are few published reports on the clinical and radiological outcomes of
      commercially available composite cages. Our study aimed to provide and evaluate
      initial outcomes of a composite Ti/PEEK cage. METHODS: In this prospective single
      senior surgeon cohort study, 31 consecutive patients underwent a modified Smith
      Robinson technique under general anesthesia and relevant data were collected. The
      study patients were aged between 18 and 75 years and underwent surgery from
      November 2013 to May 2014. Indications for surgery included traumatic and
      degenerative cervical disease that was unsuitable for or unresponsive to
      conservative management. All cages were between 5 and 8 mm and packed with super
      critical fluid sterilized allograft and bone marrow aspirate before insertion.
      Patients were followed-up for a minimum of 12 months. Fusion was assessed using
      fine cut CT and anteroposterior and lateral radiographs. Clinical outcomes were
      measured using a Visual Analogue Scale, Neck Oswestry Disability Index and
      Patient's Satisfaction Index. RESULTS: Six of the original cohort were
      unavailable for adequate follow-up. The remaining 25 patients (17 men, 8 women;
      33 operative levels) were observed for a mean of 14.6 months (range, 12-16
      months). All operation levels were between C4 and C7 . Single-level operations
      were performed in 19 patients and additional plating in 14 patients. A fusion
      rate of 96% was achieved. Patients in both plated and non-plated groups
      experienced statistically significant improvements; good to excellent outcomes
      being seen in 92% of patients. There was one complication, namely recurrent
      laryngeal nerve palsy, which had partially resolved at 6 months follow-up.
      CONCLUSION: The present study shows that enhancement of PEEK cages with Ti
      endplates is a safe and effective treatment with the potential for early
      osseointegration and early radiological evidence of fusion.

PMID- 27028378
TI  - Effect of Interbody Fusion on the Remaining Discs of the Lumbar Spine in Subjects
      with Disc Degeneration.
AB  - OBJECTIVE: To study effects (stress loads) of lumbar fusion on the remaining
      segments (adjacent or not) of the lumbar spine in the setting of degenerated
      adjacent discs. METHODS: A lumbar spine finite element model was built and
      validated. The full model of the lumbar spine was a parametric finite element
      model of segments L 1-5 . Numerous hypothetical combinations of one-level lumbar
      spine fusion and one-level disc degeneration were created. These models were
      subjected to 10 Nm flexion and extension moments and the stresses on the
      endplates and consequently on the intervertebral lumbar discs measured. These
      values were compared to the stresses on healthy lumbar spine discs under the same
      load and fusion scenarios. RESULTS: Increased stress at endplates was observed
      only in the settings of L4-5 fusion and L3-4 disc degeneration (8% stress
      elevation at L2,3 in flexion or extension, and 25% elevation at L3,4 in flexion
      only). All other combinations showed less endplate stress than did the control
      model. For fusion at L3-4 and degeneration at L4-5 , the stresses in the
      endplates at the adjacent level inferior to the fused disc decreased for both
      loading disc height reductions. Stresses in flexion decreased after fusion by
      29.5% and 25.8% for degeneration I and II, respectively. Results for extension
      were similar. For fusion at L2-3 and degeneration at L4-5 , stresses in the
      endplates decreased more markedly at the degenerated (30%), than at the fused
      level (14%) in the presence of 25% disc height reduction and 10 Nm flexion,
      whereas in extension stresses decreased more at the fused (24.3%) than the
      degenerated level (5.86%). For fusion at L3-4 and degeneration at L2-3 , there
      were no increases in endplate stress in any scenario. For fusion at L4-5 and
      degeneration at L3-4 , progression of degeneration from I to II had a significant
      effect only in flexion. A dramatic increase in stress was noted in the endplates
      of the degenerated disc (L3-4 ) in flexion for degeneration II. CONCLUSIONS:
      Stresses are greater in flexion at the endplates of L3-4 and in flexion and
      extension at L2-3 in the presence of L3-4 disc disease and L4-5 fusion than in
      the control group. In all other combinations of fusion and disc disease, endplate
      stress was less for all levels tested than in the control model.

PMID- 27028379
TI  - Circumferential Decompression via a ModifiedCostotransversectomy Approach for the
      Treatment of Single Level Hard Herniated Disc between T10 -L1.
AB  - OBJECTIVE: To describe a novel surgical strategy for circumferentially
      decompressing the T10 -L1 spinal canal when impinged upon by single level hard
      thoracic herniated disc (HTHD) via a modified costotransversectomy approach.
      METHODS: This is a retrospective review of 26 patients (17 men, 9 women; mean age
      at surgery 48.5 years, range 20-77 years) who had undergone single level HTHD
      between T10 -L1 by circumferential decompression via a modified
      costotransversectomy approach. The characteristics of the approach are using a
      posterior midline covered incision, which keeps the paraspinal muscle intact and
      ensures direct visualization of circumferential spinal cord decompression of
      single level HTHD between T10 -L1 . RESULTS: The average operative time was 208
      +/- 36 min (range, 154-300 min), mean blood loss 789 +/- 361 mL (range, 300-2000
      mL), mean preoperative and postoperative mJOA scores 5.2 +/- 1.5 and 9.0 +/- 1.3,
      respectively (t = 19.7, P < 0.05). The rate of recovery of neurological function
      ranged from 33.3% to 100%. The ASIA grade improved in 24 patients (92.3%) and
      stabilized (no grade change) in two (7.7%). MRI indicated that the cross
      sectional area of the dural sac at the level of maximum compression increased
      from 45.0 +/- 5.8 mm(2) preoperatively to 113.5 +/- 6.1 mm(2) postoperatively (t
      = 68.2, P < 0.05). Anterior tibialis muscle strength of the 15 patients with foot
      drop had a mean recovery rate of 95% at final follow-up. One patient who resumed
      work early after the surgery showed a significantly augmented Cobb angle. One
      patient had transient postoperative cerebrospinal fluid leakage. No patients
      showed neurological deterioration. CONCLUSIONS: This procedure achieves
      sufficient direct visualization for circumferential decompression of the spinal
      cord via a posterior midline covered costotransversectomy approach with friendly
      bleeding control and without muscle sacrifice. It is a reasonable alternative
      treatment option for thoracic myelopathy caused by single level HTHD between T10 
      L1 .

PMID- 27028380
TI  - Mini-invasive Transforaminal Lumbar Interbody Fusion through Wiltse Approach to
      Treating Lumbar Spondylolytic Spondylolisthesis.
AB  - OBJECTIVE: To assess the clinical efficacy of mini-invasive transforaminal lumbar
      interbody fusion (TLIF) through the Wiltse approach for treating lumbar
      spondylolytic spondylolisthesis. METHODS: In this retrospective controlled study,
      69 cases with lumbar spondylolytic spondylolisthesis treated in Qilu hospital
      from April to November 2014 were randomly assigned to Wiltse approach (31 cases,
      16 male, 15 female; mean age 45.1 years) and traditional approach groups (38
      cases, 21 male, 17 female; 47.2 years. In the Wiltse approach group, the affected
      level was L4, 5 in 19 cases and L5 S1 in 12, 9 of whom had low back pain (LBP)
      only and 21 both LBP and leg pain. There were 17 cases of I degree and 14 of II
      degree spondylolisthesis. Pre-operative Japanese Orthopedic Association (JOA)
      score was 13.1 +/- 2.6; visual analog scale (VAS) for LBP 7.4 +/- 1.2; VAS for
      leg pain 6.1 +/- 2.0 and Oswestry disability index (ODI) score 42.2% +/- 1.2%. In
      the traditional approach group, the affected level was L4, 5 in 22 cases and L5
      S1 in 16, 11 of whom had LBP only and 27 both LBP and leg pain. There were 21
      cases of I degree and 17 of II degree spondylolisthesis. Pre-operative JOA score
      was 12.8 +/- 1.2; VAS for LBP 6.9 +/- 1.1; VAS for leg pain 7.1 +/- 2.0 and ODI
      score 41.2% +/- 2.0%. The JOA score, VAS for LBP and leg pain, ODI dynamic X
      rays, CT and/or MR were evaluated 3 and 6 months and 1 year postoperatively.
      RESULTS: There were no differences in sex, age, affected levels,
      spondylolisthesis degree, pre-operative JOA score, VAS for LBP or leg pain and
      ODI score between the two groups (P > 0.05). The incision length, blood loss and
      time to achieving exposure were better in the Wiltse approach than the
      traditional approach group (P < 0.05). The VAS for LBP and muscle atrophy MRI
      scores were significantly lower in the Wiltse approach than the traditional
      approach group on Days 1 and 14 and at 1 year follow-up (P < 0.05). The VAS for
      leg pain, JOA recovery rate and JOA and ODI scores tended to be lower in the
      Wiltse approach than the traditional approach group at 1 year follow-up
      examinations (no differences statistically significant, P > 0.05). The interbody
      fusion rate was not significantly different between the groups (P > 0.05). There
      were no complications of internal fixation in either group. CONCLUSION: TLIF via
      both approaches has satisfactory clinical efficacy. TLIF through the Wiltse
      approach significantly reduces the damage of multifidus and postoperative
      incidence of chronic LBP.

PMID- 27028381
TI  - Open Patellar Tendon Tenotomy and Debridement Combined with Suture-bridging
      Double-row Technique for Severe Patellar Tendinopathy.
AB  - OBJECTIVE: To create a new surgical procedure for chronic severe patellar
      tendinopathy and to evaluate its clinical efficacy. METHODS: In this
      retrospective study, the data of 12 patients with severe patellar tendinopathy in
      14 knees who had undergone surgical treatment at Beijing Chao-Yang Hospital
      between 1 March 2009 and 1 August 2013 were analyzed. Inclusion criteria included
      severe patellar tendinopathy (Phase III), conservative therapy for more than 6
      months, American Society of Anesthesiology status Grade I-II, and body mass index
      <30. Patients with severe osteoporosis, complete tendon disruption (Phase IV) and
      those who were unable to cooperate were excluded. There were 8 men (10 knees) and
      4 women (4 knees) cases. The patients' ages ranged from 38 to 54 years (mean,
      45.3 years). All surgeries had been performed by the same physician. Surgical
      treatment comprised incising open patellar midline tenotomy, complete debridement
      and suture-bridging double-row fixation. Isotonic and kinetic chain exercises
      were implemented after the second post-operative week. A gradual increase to full
      weight-bearing was allowed after the third post-operative week and a gradual
      return to unrestricted use of the leg after the eighth post-operative week.
      Preoperative and postoperative visual analogue scale (VAS) scores and Lysholm
      knee scores were obtained from the medical records or at recent postoperative
      follow-up visits and the results compared using Student's two-tailed paired t
      test. RESULTS: VAS scores decreased by a mean of 6.7 points (range, 1.1-7.8
      points) during follow-up (minimum duration 14 months; range, 14-44 months) and
      Lysholm scores increased from 55.7 +/- 6.5 points to 90.4 +/- 6.2 points. Three
      cases (4 knees) achieved excellent outcomes (>=95 points) and 9 cases (10 knees)
      good outcomes (range, 86-94 points). No intraoperative or postoperative
      complications occurred. There were significant differences between preoperative
      and postoperative VAS and Lysholm scores (P < 0.01). CONCLUSIONS: All study
      patients achieved good or excellent outcomes. No patellar tendon rupture or
      suture fixation failure occurred during follow-up. Suture-bridging double-row
      fixation is a simple and reliable method that not only improves patients'
      clinical symptoms, but also restores knee joint function.

PMID- 27028382
TI  - Perioperative Period of a Hemophilia-related Osteoarthropathy Therapeutic Regimen
      and Analysis of Complications.
AB  - OBJECTIVE: To investigate the effectiveness of our department's therapeutic
      regimen and treatment of complications during the perioperative period of
      hemophilia-related osteoarthropathy. METHODS: In this retrospective study, data
      on 101 patients with hemophilia who had undergone operative treatment in our
      hospital from January 2000 to August 2014 were assessed. Ninety-one of the
      patients had hemophilia A and 10 hemophilia B. All patients were male. Changes in
      Hospital for Special Surgery (HSS), Harris and American Orthopedic Foot and Ankle
      Society (AOFAS) scores, occurrence of complications during the perioperative
      period and the clinical treatment and prognosis pre- and postoperatively and
      during follow-up were analyzed. Relevant clinical data were obtained through
      telephone calls, outpatient follow-up, and medical clinical record searches.
      RESULTS: The 101 patients who were followed up (for an average of 96 months) had
      147 orthopedic operations, including joint replacement, hemophilia-related false
      tumor resections, and tendo-achillis lengthening. The HSS scores for knee
      surgeries increased from 52 points preoperatively to 86 postoperatively, Harris
      scores for hip joint surgery from 26 to 87 points, respectively, and AOFAS scores
      for foot and ankle surgeries from 39 to 81 points, respectively. Eight patients
      had wound complications, four intra-articular hematomas, two peroneal nerve
      injuries, one a proximal femur splitting fracture and one deep venous thrombosis.
      CONCLUSIONS: Surgical treatment is a safe and reliable choice for addressing
      complications including hemophilia-related osteoarthropathy given the
      implementation of effective measures for treatment during the perioperative
      period.

PMID- 27028383
TI  - Effect of a New Annular Incision on Biomechanical Properties of the
      Intervertebral Disc.
AB  - OBJECTIVE: To compare the biomechanical properties of a novel annular incision
      technique, an oblique incision made approximately 60 degrees  to the spinal
      column, with the traditional transverse and longitudinal annular slit incision in
      an ex vivo sheep lumbar spine model. METHODS: Sixteen sheep lumbar spines were
      used for the current ex vivo biomechanical comparative study. Functional spine
      unit (FSU) specimens composed of two vertebrae and one disc in the middle was cut
      from the whole lumbar spine. Annular slit incisions of 5 mm were made in
      different directions with a 15-blade knife at the intervertebral disc, following
      which partial discectomy was performed to produce the following groups: control
      with no incision, transverse slit, longitudinal slit and oblique slit groups. The
      specimens were then subjected to flexion-extension, lateral bending, axial
      rotation and compression tests. RESULTS: As expected, the control group showed
      the least range of motion (ROM) in the flexion-extension test. The oblique slit
      group showed a trend toward a smaller ROM than the transverse and longitudinal
      groups in 1, 2, 3 and 5 Nm flexion-extension tests; these differences were not
      statistically significant (P > 0.05). In addition, the transverse (5.80 degrees 
      +/- 0.20 degrees ), longitudinal (5.77 degrees  +/- 0.67 degrees ) and oblique
      (5.47 degrees  +/- 0.43 degrees ) slit groups showed a significantly larger ROM
      than the control group (3.22 degrees  +/- 0.28 degrees ) in 2 Nm lateral bending
      tests (P < 0.05). Compared with the transverse and longitudinal groups, the
      oblique group also showed a trend toward a smaller ROM in lateral bending tests
      (P > 0.05). Following increments in the axial torsion force, the ROM was greater
      in all four experimental groups than the ROM with 1 Nm axial torsion.
      Furthermore, a significantly smaller axial rotational ROM was found in the
      oblique than the transverse group for 1 and 5 Nm force (P < 0.05). With increase
      in the axial force to 5 Nm, the ROM in the oblique slit group (4.71 degrees  +/-
      0.52 degrees ) was significantly smaller than that in the transverse group (7.25
      degrees  +/- 0.46 degrees , P < 0.05), but not significantly different from that
      of the longitudinal slit group (5.84 degrees  +/- 0.23 degrees , P > 0.05).
      Comparable ultimate loads to failure were found in the oblique, transverse and
      longitudinal groups; the highest ultimate load to failure being in the control
      group (P > 0.05). CONCLUSION: The novel oblique slit annular incision to the
      intervertebral disc showed a trend toward better biomechanical properties than
      the traditional transverse and longitudinal slit incisions.

PMID- 27028384
TI  - Clinical Significance of a Novel Knee Joint Stability Assessment System for
      Evaluating Anterior Cruciate Ligament Deficient Knees.
AB  - OBJECTIVE: To investigate the six degrees of freedom (6DOF) kinematics of
      anterior cruciate ligament (ACL) deficient knees during gait and to explore the
      clinical significance of a novel knee joint stability assessment system
      (Opti_Knee, Innomotion, Shanghai, China) in comparison with imaging and
      arthroscopic examination. METHODS: Three subjects diagnosed with ACL deficient
      knees on the basis of preoperative MRI and CT findings were subjected to
      treadmill gait analysis. Motion of both knees in 6DOF was measured and analyzed
      with an optical joint kinematics measurement system. Arthroscopic examination,
      the gold standard, was performed to confirm the final diagnosis and the clinical
      diagnosis of ACL deficiency by imaging and motion marker techniques compared with
      this gold standard. RESULTS: Only two of the three subjects diagnosed with ACL
      deficiency by imaging techniques were later confirmed to have this condition by
      arthroscopic examination; the third was found to have an intact ACL. When the
      kinematics of their injured and contralateral knees were compared, abnormalities
      were found in the two subjects confirmed by arthroscopy to be ACL deficient
      However, no kinematic difference between the two knees was found in the ACL
      intact subject. CONCLUSIONS: Opti_Knee (Innomotion) can detect abnormal
      kinematics in ACL deficient knees and thus provides an effective way of assisting
      the diagnosis of this condition and has potential for clinical application.

PMID- 27028385
TI  - S2 Alar-iliac Fixation: A Powerful Procedure for the Treatment of Kyphoscoliosis.
AB  - The purpose of this study was to introduce a powerful technique for the treatment
      of kyphoscoliosis. There are currently multiple techniques for sacropelvic
      fixation, including trans-iliac bars and iliac and iliosacral screws. Several
      studies have documented the use of these instrumentation techniques; however, a
      ubiquitous problematic issue concerns the need for separate incisions for the use
      of offset connectors, which add to surgical time and morbidity. Any additional
      dissection of the skin, subcutaneous tissue or muscle in this area is believed to
      increase the incidence of complications of wound healing. However, as stated
      above, the above-mentioned techniques require separate incisions for the use of
      offset connectors, which add to surgical time and morbidity. The novel technique
      of S2 alar-iliac (S2AI) pelvic fixation has been developed to address some of
      these issues. However, a technique for achieving correction of kyphoscoliosis
      with pelvic obliquity in adult patients with spinal deformity has not previously
      been described. Our entry point is based on the S1 foramen and is typically up to
      5 mm caudal and 2 to 3 mm lateral to that foramen. Once the S1 foramen has been
      identified, a blunt instrument can be used to probe the alar ridge. The screw
      trajectory is 40 degrees -50 degrees  from horizontal and 20 degrees -30 degrees 
      caudal, aimed toward the greater trochanter and rostral to the sciatic notch. A
      36-year-old female patient presented with a 3-year history of low back pain, and
      progressive thoracolumbar kyphoscoliosis. In this typical case, we performed S2AI
      fixation with transforaminal lumbar interbody fusion and hemivertebra resection
      technique to treat her lumbosacral kyphoscoliosis. Satisfactory improvement in
      her preoperative lumbar kyphoscoliosis was found at 3-month follow-up. 

PMID- 27028386
TI  - Double Dislocation of Interphalangeal Joints Accompanied with Contralateral
      Shoulder Dislocation: A Case Report.
AB  - Dislocation of any joint is an orthopaedic emergency and needs immediate
      attention by the attending physician. A delay in reducing a dislocated joint can
      lead to disastrous complications both immediately as well as in the long run.
      Although anterior dislocation of a shoulder joint is by far the commonest
      dislocation encountered by any emergency care physician, other joints may also
      get dislocated. In certain cases two joints may get dislocated simultaneously.
      Such dislocation is known as a double dislocation. Double dislocation of the
      proximal interphalangeal joint and the distal interphalangeal joint in the same
      finger is a rare injury. High impact loading at the fingertip is the primary
      cause in most cases and it is often associated with younger individuals playing
      contact sports. The right little finger is the digit commonly involved and this
      injury is evident in football players more often than not. Although closed
      reduction is a preferred treatment, it may not be always successful. Time of
      presentation, tendon interposition, associated swelling and co-existent
      phalangeal fractures are certain key impediments to a successful closed reduction
      manoeuvre. In patients with an open injury, a thorough wash out and appropriate
      antibiotic cover is mandatory. We report a rare case of double dislocation of the
      interphalangeal joints accompanied with contralateral shoulder dislocation in an
      elderly man sustained after a fall which was treated successfully with closed
      reduction and early mobilization. 

PMID- 27028387
TI  - Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal
      Fixation via Posterior Approach Only.
AB  - Surgical treatment for spinal tuberculosis includes focal tuberculosis
      debridement, segmental stability reconstruction, neural decompression and
      kyphotic deformity correction. For the lesions mainly involved anterior and
      middle column of the spine, anterior operation of debridement and fusion with
      internal fixation has been becoming the most frequently used surgical technique
      for the spinal tuberculosis. However, high risk of structural damage might relate
      with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel,
      and the deformity correction is also limited. Due to the organs are in the front
      of spine, there are less complications in posterior approach. Spinal pedicle
      screw passes through the spinal three-column structure, which provides more
      powerful orthopedic forces compared with the vertebral body screw, and the
      kyphotic deformity correction effect is better in posterior approach. In this
      paper, we report a 68-year-old male patient with thoracic tuberculosis who
      underwent surgical treatment by debridement, interbody fusion and internal
      fixation via posterior approach only. The patient was placed in prone position
      under general anesthesia. Posterior midline incision was performed, and the
      posterior spinal construction was exposed. Then place pedicle screw, and fix one
      side rod temporarily. Make the side of more bone destruction and larger abscess
      as lesion debridement side. Resect the unilateral facet joint, and retain
      contralateral structure integrity. Protect the spinal cord, nerve root. Clear
      sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space.
      Specially designed titanium mesh cages or bone blocks were implanted into
      interbody. Fix both side rods and compress both sides to make the mesh cages and
      bone blocks tight. Reconstruct posterior column structure with allogeneic bone
      and autologous bone. Using this technique, the procedures of debridement, spinal
      cord decompression, deformity correction, bone grafting, and internal fixation
      can be completed with only one incision and surgical position, and the deformity
      correction efficiency is higher than anterior surgery. 

PMID- 27028388
TI  - Pathology Reports: A Second Look.

PMID- 27028389
TI  - Pathology Residents Are Not "Trainees".

PMID- 27028390
TI  - The Pulmonary Pathology Society's Future: Busy and Bright.

PMID- 27028391
TI  - Impact of Recent Developments in Lung Cancer on the Practice of Pathology.
AB  - Landmark events in the field of lung cancer in the past year have the potential
      to significantly alter the practice of pathology. Three key events are (1)
      approval of payment for low-dose computed tomography screening for lung cancer,
      (2) publication of an extensively revised World Health Organization
      classification of lung cancers, and (3) approval of immunohistochemistry based
      companion diagnostics by the US Food and Drug Administration. We briefly review
      these milestones in the context of their impact on the practice of pathology. 

PMID- 27028392
TI  - Ribonucleic Acid In Situ Hybridization Is a More Sensitive Method Than
      Immunohistochemistry in Detection of Thyroid Transcription Factor 1 and Napsin A
      Expression in Lung Adenocarcinomas.
AB  - CONTEXT: TTF-1 and napsin A immunomarkers have a crucial role in differentiating
      lung adenocarcinoma from lung squamous cell carcinoma and in identifying a
      primary lung adenocarcinoma when working on a tumor of unknown origin.
      OBJECTIVES: To investigate the diagnostic sensitivity of ribonucleic acid in situ
      hybridization (RNAscope) in the detection of expression of these biomarkers in
      lung adenocarcinomas and to compare RNAscope to immunohistochemical techniques.
      DESIGN: Both RNAscope and the immunohistochemical assays for TTF-1 and napsin A
      were performed on tissue microarray sections containing 80 lung adenocarcinomas
      and 80 lung squamous cell carcinomas. The RNAscope assay for both TTF-1 and
      napsin A was also performed on 220 adenocarcinomas from various organs. RESULTS:
      The RNAscope assay for TTF-1 gave positive results in 92.5% (74 of 80) of the
      lung adenocarcinomas; in contrast, immunohistochemistry gave positive results in
      82.5% (66 of 80) of those cases. The RNAscope assay for napsin A gave positive
      results in 90% (72 of 80) of lung adenocarcinomas; immunohistochemistry results
      were positive in 77.5% (62 of 80) of those cases. Napsin A expression was not
      seen in lung squamous cell carcinomas by either method. In contrast, TTF-1
      expression was seen in 3.8% (3 of 80) (1(+)) and 10% (8 of 80) (1(+)) of the
      squamous cell carcinomas by immunochemistry and the RNAscope, respectively. All
      nonpulmonary adenocarcinoma results were negative for TTF-1 by the RNAscope
      assay. CONCLUSIONS: Preliminary data suggest that RNAscope is superior to
      immunohistochemistry in detecting TTF-1 and napsin A expression in primary lung
      adenocarcinomas. Therefore, performing an RNAscope assay may be considered for
      both TTF-1(-) and napsin A(-) cases with a clinical suspicion of lung
      adenocarcinoma. The TTF-1 results should be interpreted with caution because a
      small percentage of squamous cell carcinomas can be focally positive by either
      assay.

PMID- 27028393
TI  - Acute Lung Injury: A Clinical and Molecular Review.
AB  - CONTEXT: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)
      are a continuum of lung changes arising from a wide variety of lung injuries,
      frequently resulting in significant morbidity and frequently in death. Research
      regarding the molecular pathophysiology of ALI/ARDS is ongoing, with the aim
      toward developing prognostic molecular biomarkers and molecular-based therapy.
      OBJECTIVE: To review the clinical, radiologic, and pathologic features of
      ALI/ARDS; and the molecular pathophysiology of ALI/ARDS, with consideration of
      possible predictive/prognostic molecular biomarkers and possible molecular-based
      therapies. DATA SOURCES: Examination of the English-language medical literature
      regarding ALI and ARDS. CONCLUSIONS: ARDS is primarily a clinicoradiologic
      diagnosis; however, lung biopsy plays an important diagnostic role in certain
      cases. A significant amount of progress has been made in the elucidation of ARDS
      pathophysiology and in predicting patient response, however, currently there is
      no viable predictive molecular biomarkers for predicting the severity of ARDS, or
      molecular-based ARDS therapies. The proinflammatory cytokines TNF-alpha (tumor
      necrosis factor alpha), interleukin (IL)-1beta, IL-6, IL-8, and IL-18 are among
      the most promising as biomarkers for predicting morbidity and mortality.

PMID- 27028394
TI  - Clinical and Cost Implications of Universal Versus Locally Advanced-Stage and
      Advanced-Stage-Only Molecular Testing for Epidermal Growth Factor Receptor
      Mutations and Anaplastic Lymphoma Kinase Rearrangements in Non-Small Cell Lung
      Carcinoma: A Tertiary Academic Institution Experience.
AB  - CONTEXT: Although epidermal growth factor receptor (EGFR)- and anaplastic
      lymphoma kinase (ALK)-directed therapies are not approved for patients with early
      stage non-small cell lung carcinoma (NSCLC), many institutions perform EGFR and
      ALK testing for all patients with NSCLC at the time of initial diagnosis. Current
      consensus guidelines recommend EGFR testing and suggest ALK testing at the time
      of initial diagnosis for patients with advanced disease. OBJECTIVES: To examine
      the cost and clinical impact of EGFR and ALK testing of patients with early-stage
      NSCLC. DESIGN: Records from all patients with a diagnosis of NSCLC made on a
      nonresection specimen at our institution during a single calendar year (2012)
      were reviewed, and a cost analysis was performed. RESULTS: Of 133 total patients,
      47 (35%) had early-stage (stage I or II) disease and 86 (65%) had locally
      advanced (stage III) or advanced (stage IV) disease at presentation. Eight of 47
      patients with early-stage disease (17%) had progression/recurrence during 18 to
      30 months of follow-up, 6 of 8 (75%) of whom had pathologic confirmation of
      progression/recurrence. The estimated additional cost of EGFR and ALK testing for
      all newly diagnosed patients with NSCLC at our institution is $75,200 per year,
      compared to testing only patients with locally advanced and advanced-stage
      disease. CONCLUSIONS: The cost of universal molecular testing of NSCLC is
      substantial. EGFR and ALK testing of patients with early-stage disease appears to
      have negligible clinical impact, as most patients do not have disease
      recurrence/progression. Those whose disease recurs/progresses typically undergo
      rebiopsy. Our findings do not support the practice of universal EGFR and ALK
      testing in NSCLC at the time of initial diagnosis.

PMID- 27028395
TI  - Ossifying Fibromyxoid Tumor: An Update.
AB  - Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain
      differentiation, initially described by Enzinger and colleagues. Until now,
      nearly 300 such cases have been reported worldwide. The histogenesis of these
      tumors remains controversial. These tumors show characteristic imaging findings
      and exhibit a spectrum of histopathologic features, including classical and
      atypical subtypes. Local recurrences and, occasionally, distant metastases have
      also been reported. A complete tumor resection forms the preferred treatment
      modality for these tumors, along with follow-up, as these tumors have an
      uncertain malignant potential. Lately, certain "molecular signatures" underlying
      OFMTs have been described that can further aid in reaching an accurate diagnosis
      for these tumors and unraveling their pathogenesis. This article is a review of
      the clinical, radiologic, histopathologic, and molecular features of OFMTs. 

PMID- 27028396
TI  - Atypical Fibroxanthoma.
AB  - Atypical fibroxanthoma is a malignant skin tumor with histologic features similar
      to those of undifferentiated pleomorphic sarcoma, but lacking its more aggressive
      behavior. The tumor is composed of pleomorphic cells with hyperchromatic nuclei
      and abundant cytoplasm, commonly arranged in a spindle cell pattern. Recent
      genetic studies have identified similarities between atypical fibroxanthoma and
      undifferentiated pleomorphic sarcoma, such as the presence of 9p and 13q
      deletions in both tumors, favoring a common histogenesis. However, the lack of K
      ras and H-ras mutations in atypical fibroxanthoma compared with undifferentiated
      pleomorphic sarcoma could explain the difference in aggressiveness and continued
      separation of these entities. Exclusion of other neoplasms by histology and
      immunohistochemistry followed by complete surgical removal remains the standard
      of care. 

PMID- 27028397
TI  - Sickle cell disease in western Sudan: genetic epidemiology and predictors of
      knowledge attitude and practices.
AB  - OBJECTIVE: To investigate the epidemiology of sickle cell disease (SCD) and
      determinants of knowledge, attitudes and practices (KAP) towards SCD in western
      Kordofan State, Sudan. METHODS: A community-based, descriptive, cross-sectional
      study was conducted in three towns. Three hundred and seventy-two households were
      polled, and blood samples for haemoglobin phenotyping were collected from 1116
      individuals. Sociodemographic, socio-economic and KAP data were collected using
      investigator-administered questionnaires. Descriptive, frequency distribution and
      multiple regression analyses were performed. RESULTS: About 50.9% of the study
      population were Misseriya tribes. Consanguineous marriages were reported by 67.5%
      of the households. The highest percentage of homozygous SCD was 2.8% among
      children under 5 years of age. About 24.9% were carriers of HbS allele (HbAS).
      HbS allele frequency was highest in children aged 5-11 years (18.3%, CI: 13.7
      22.9%) and lowest in males >15 years old (12.0%, CI: 6.1-17.9%). The average HbS
      frequency across all age groups was 14.5% (95% CI: 12.2-16.8%). The most frequent
      beta-globin gene cluster haplotype was the Cameroon (30.8%), followed by the
      Benin (21.8%), the Senegal (12.8%) and the Bantu (2.2%) haplotypes. About 17.0%
      of all-cause child deaths were due to SCD. The estimated change in log odds of
      having the SS genotype per year increase in age was (-) 0.0058 (95% CI -0.0359,
      0.0242). This represents a non-statistically significant 2.9% increase in 5-year
      mortality for individuals with the SS genotype relative to those with AS and AA
      genotypes. About 46.9% of the households had poor knowledge, 26.1% had
      satisfactory knowledge, and 26.9% had good knowledge about sickle cell disease.
      Mothers' and fathers' educational levels were significant predictors of good
      knowledge about SCD (P < 0.05). About 48.0% had a satisfactory attitude towards
      sickle cell disease while 30.7% had poor attitude and only 21.3 showed good
      attitudes. Poor knowledge about SCD and low socio-economic status were the
      strongest positive predictors of poor attitude and practices towards SCD (P <
      0.01). CONCLUSIONS: Sickle cell disease is a major health problem in West
      Kordofan, Sudan. Knowledge, attitude and practices towards the disease are not
      satisfactory. The development of public health programs is highly recommended to
      control and manage SCD in western parts of Sudan.

PMID- 27028398
TI  - Inflation-Fixation Method for Lipidomic Mapping of Lung Biopsies by Matrix
      Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging.
AB  - Chronic respiratory diseases are among the leading causes of deaths worldwide and
      major contributors of morbidity and global disease burden. To appropriately
      investigate lung disease, the respiratory airways must be fixed in their
      physiological orientation and should be inflated prior to investigations. We
      present an inflation-fixation method that enables lipidomic investigations of
      whole lung samples and resected biopsy specimens by matrix-assisted laser
      desorption/ionization-mass spectrometry imaging (MALDI-MSI). Formalin-inflation
      enables sample preparation to parallel standard clinical and surgical procedures,
      in addition to greatly reducing the complexity of analysis, by decreasing the
      number of analytes in the MALDI plume and reducing adduct formation in the
      resulting mass spectra. The reduced complexity increased sensitivity and enabled
      high-resolution imaging acquisitions without any loss in analyte detection at 10
      and 20 MUm scans. We present a detailed study of over 100 lipid ions detected in
      positive and negative ion modes covering the conducting and respiratory airways
      and parts of the peripheral nervous tissue running through the lungs. By defining
      the resolution required for clear definition of the alveolar space and thus the
      respiratory airways we have provided a guideline for MSI investigations of
      respiratory diseases involving the airways, including the interstitium. This
      study has provided a detailed map of lipid species and their localization within
      larger mammalian lung samples, for the first time, thus categorizing the lipidome
      for future MALDI-MSI studies of pulmonary diseases.

PMID- 27028399
TI  - Analysis of the Capacity of Google Trends to Measure Interest in Conservation
      Topics and the Role of Online News.
AB  - With the continuous growth of internet usage, Google Trends has emerged as a
      source of information to investigate how social trends evolve over time. Knowing
      how the level of interest in conservation topics--approximated using Google
      search volume--varies over time can help support targeted conservation science
      communication. However, the evolution of search volume over time and the
      mechanisms that drive peaks in searches are poorly understood. We conducted time
      series analyses on Google search data from 2004 to 2013 to investigate: (i)
      whether interests in selected conservation topics have declined and (ii) the
      effect of news reporting and academic publishing on search volume. Although
      trends were sensitive to the term used as benchmark, we did not find that public
      interest towards conservation topics such as climate change, ecosystem services,
      deforestation, orangutan, invasive species and habitat loss was declining. We
      found, however, a robust downward trend for endangered species and an upward
      trend for ecosystem services. The quantity of news articles was related to
      patterns in Google search volume, whereas the number of research articles was not
      a good predictor but lagged behind Google search volume, indicating the role of
      news in the transfer of conservation science to the public.

PMID- 27028400
TI  - Role of DNA methylation in cardiovascular diseases.
AB  - A complex interplay between genetic and environmental factors is involved in the
      pathogenesis of cardiovascular diseases (CVDs). Environmental factors have
      crucial effects on the epigenetic trait of genes, which refers to a stably
      heritable phenotype resulting from changes in the chromosomes without alteration
      of the DNA sequence, but has profound effects on the cellular repertoire. Among
      the epigenetic patterns, DNA methylation is of great interest. DNA methylation
      occurs at both global and specific gene promoter levels and relates to
      atherosclerosis. Aberrant DNA methylation affects the transcription and
      expression of critical regulatory genes and induces a proatherogenic cellular
      phenotype, which plays key roles in endothelia cell dysfunction, abnormal
      vascular smooth muscle cell proliferation, extracellular matrix formation, and
      inflammation in CVDs. This review focuses on the contribution of DNA methylation
      in the pathogenesis of CVDs. 

PMID- 27028402
TI  - An International Collaborative Study to establish the World Health Organization
      4th International Standard for Plasmin (13/206): communication from the SSC of
      the ISTH.

PMID- 27028403
TI  - Impact of a population-wide mental health promotion campaign on people with a
      diagnosed mental illness or recent mental health problem.
AB  - OBJECTIVES: To determine the impact of the Act-Belong-Commit mental health
      promotion campaign on people with a diagnosed mental illness or who had sought
      professional help for a mental health problem in the previous 12 months. METHOD:
      In 2013 and 2014, 1,200 adults in Western Australia were interviewed by
      telephone. The questionnaire measured campaign reach, impact on beliefs about
      mental health and mental illness and behavioural impact. RESULTS: Campaign impact
      on changing the way respondents thought about mental health was significantly
      higher among those with a mental illness or who had sought help (41.4% vs 24.2%;
      p<0.001), as was doing something for their mental health as a result of their
      exposure to the campaign (20.5% vs 8.7%; p<0.001). CONCLUSIONS: The campaign
      appears to empower people with a mental illness or who recently sought help to
      take steps of their own to enhance their mental health.

PMID- 27028404
TI  - Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe
      Chronic Central Post-Stroke Pain Patient: A Case Study.
AB  - Central post-stroke pain is a neuropathic syndrome characterized by intolerable
      contralesional pain and, in rare cases, somatic delusions. To date, there is
      limited evidence for the effective treatments of this disease. Here we used
      caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year
      old woman suffering from central post-stroke pain. Resting-state functional
      magnetic resonance imaging was used to assess the neurological effects of this
      treatment. Following vestibular stimulation we observed impressive improvements
      in motor skills, pain, and somatic delusions. In the functional connectivity
      study before the vestibular stimulation, we observed differences in the patient's
      left thalamus functional connectivity, with respect to the thalamus connectivity
      of a control group (N = 20), in the bilateral cingulate cortex and left insula.
      After the caloric stimulation, the left thalamus functional connectivity with
      these regions, which are known to be involved in the cortical response to pain,
      disappeared as in the control group. The beneficial use of vestibular stimulation
      in the reduction of pain and somatic delusion in a CPSP patient is now documented
      by behavioral and imaging data. This evidence can be applied to theoretical
      models of pain and body delusions. 

PMID- 27028405
TI  - Establishment and Biological Characterization of a Panel of Glioblastoma
      Multiforme (GBM) and GBM Variant Oncosphere Cell Lines.
AB  - OBJECTIVE: Human tumor cell lines form the basis of the majority of present day
      laboratory cancer research. These models are vital to studying the molecular
      biology of tumors and preclinical testing of new therapies. When compared to
      traditional adherent cell lines, suspension cell lines recapitulate the genetic
      profiles and histologic features of glioblastoma multiforme (GBM) with higher
      fidelity. Using a modified neural stem cell culture technique, here we report the
      characterization of GBM cell lines including GBM variants. METHODS: Tumor tissue
      samples were obtained intra-operatively and cultured in neural stem cell
      conditions containing growth factors. Tumor lines were characterized in vitro
      using differentiation assays followed by immunostaining for lineage-specific
      markers. In vivo tumor formation was assayed by orthotopic injection in nude
      mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA
      profiling. RESULTS: Thirteen oncosphere lines derived from GBM and GBM variants,
      including a GBM with PNET features and a GBM with oligodendroglioma component,
      were established. All unique lines showed distinct genetic profiles by STR
      profiling. The lines assayed demonstrated a range of in vitro growth rates.
      Multipotency was confirmed using in vitro differentiation. Tumor formation
      demonstrated histologic features consistent with high grade gliomas, including
      invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts
      derived from the GBM variants maintained histopathological features of the
      primary tumors. CONCLUSIONS: We have generated and characterized GBM suspension
      lines derived from patients with GBMs and GBM variants. These oncosphere cell
      lines will expand the resources available for preclinical study.

PMID- 27028406
TI  - Endothelial Dysfunction and Racial Disparities in Mortality and Adverse
      Cardiovascular Disease Outcomes.
AB  - BACKGROUND: The contribution of arterial endothelial dysfunction (ED) to
      increased cardiovascular disease (CVD) risk among Blacks is not known.
      HYPOTHESIS: We investigated whether peripheral arterial ED explains racial
      disparity in CVD events. METHODS: Data from the Heart Strategies Concentrating on
      Risk Evaluation (Heart SCORE) study was used. Endothelial dysfunction was
      assessed by the Framingham reactive hyperemia index (fRHI), measured using pulse
      amplitude tonometry (PAT). Lower values of fRHI indicate more severe ED. The
      primary outcome of interest was combined CVD events and all-cause mortality.
      RESULTS: 1454 individuals (62% female, 40% Black, mean age 59 +/- 8 years) had
      available data on fRHI (mean [SD]: 0.74 [0.46]). Over a mean follow-up period of
      8.0 +/- 2.4 years (11,186 person-years), 116 events were observed. Black race,
      male sex, smoking, diabetes, blood pressure, triglycerides, C-reactive protein,
      and interleukin-6 were inversely correlated with fRHI in univariate models. In an
      unadjusted Cox regression model, fRHI was associated with 20% lower risk of the
      primary outcome events (hazard ratio [HR] per 1-SD higher fRHI: 0.80, 95%
      confidence interval [CI]: 0.66-0.97). However, this association was no longer
      significant after adjustment for CVD risk factors (HR: 0.90, 95% CI: 0.74-1.11).
      In an age- and sex-adjusted model, Blacks had 1.68 (95% CI: 1.16-2.43) higher
      risk of primary outcome compared with Whites. This association was not
      significantly attenuated by addition of fRHI to the multivariable models.
      CONCLUSION: Black race is associated with increased risk of CVD events and
      mortality independent of its associations with ED, as measured by PAT.

PMID- 27028407
TI  - Novel anticoagulants - an update on the latest developments and management for
      clinicians treating patients on these drugs.
AB  - There are several novel anticoagulant agents that are being increasingly used as
      an alternative to warfarin, with these drugs being reported to be at least as
      effective if not better. Their increased use means that oral care clinicians
      should have a sound understanding of the mechanism of action, pharmacology,
      reversal strategies and management of bleeding in patients taking these drugs.
      Surprisingly, there is little published in the current literature specific to
      professionals involved in oral health care. In this review, we provide an
      overview of these drugs and discuss the management of patients who need an oral
      procedure based on currently available literature and clinical trials. 

PMID- 27028408
TI  - Identification and Fine Mapping of a White Husk Gene in Barley (Hordeum vulgare
      L.).
AB  - Barley is the only crop in the Poaceae family with adhering husks at maturity.
      The color of husk at barely development stage could influence the agronomic
      traits and malting qualities of grains. A barley mutant with a white husk was
      discovered from the malting barley cultivar Supi 3 and designated wh (white
      husk). Morphological changes and the genetics of white husk barley were
      investigated. Husks of the mutant were white at the heading and flowering stages
      but yellowed at maturity. The diastatic power and alpha-amino nitrogen contents
      also significantly increased in wh mutant. Transmission electron microscopy
      examination showed abnormal chloroplast development in the mutant. Genetic
      analysis of F2 and BC1F1 populations developed from a cross of wh and Yangnongpi
      5 (green husk) showed that the white husk was controlled by a single recessive
      gene (wh). The wh gene was initially mapped between 49.64 and 51.77 cM on
      chromosome 3H, which is syntenic with rice chromosome 1 where a white husk gene
      wlp1 has been isolated. The barley orthologous gene of wlp1 was sequenced from
      both parents and a 688 bp deletion identified in the wh mutant. We further fine
      mapped the wh gene between SSR markers Bmac0067 and Bmag0508a with distances of
      0.36 cM and 0.27 cM in an F2 population with 1115 individuals of white husk.
      However, the wlp1 orthologous gene was mapped outside the interval. New candidate
      genes were identified based on the barley genome sequence. 

PMID- 27028409
TI  - The effects of a cancer diagnosis on the health of a patient's partner: a
      population-based registry study of cancer in Sweden.
AB  - The aim of this population-based registry study was to explore how cancer
      influences the health of partners, by examining the onset of new diagnoses for
      partners, health care use and health care costs among partners living with
      patients with cancer. The sample consisted of partners of patients with cancer (N
      = 10 353) and partners of age- and sex-matched controls who did not have cancer
      (N = 74 592). Diagnoses, health care use and health care costs were studied for a
      continuous period starting 1 year before the date of cancer diagnosis and
      continued for 3 years. One year after cancer diagnosis, partners of patients with
      cancer had significantly more mood disorders, reactions to severe stress and
      ischaemic heart disease than they exhibited in the year before the diagnosis.
      Among partners of patients with cancer, the type of cancer was associated with
      the extent and form of increased health care use and costs; both health care use
      and costs increased among partners of patients with liver cancer, lung cancer,
      colon cancer and miscellaneous other cancers. The risk of poorer health varied
      according to the type of cancer diagnosed, and appeared related to the severity
      and prognosis of that diagnosis. 

PMID- 27028410
TI  - Lipid disorder and intrahepatic renin-angiotensin system activation
      synergistically contribute to non-alcoholic fatty liver disease.
AB  - BACKGROUND: This study aimed to investigate the possible synergistic effects of
      lipid disorder with renin-angiotensin system (RAS) activation in non-alcoholic
      fatty liver disease (NAFLD). METHODS: Apolipoprotein E gene-knockout mice,
      angiotensin II (Ang II) type 1 receptor (AT1) gene-knockout mice and human
      hepatoblastoma cell line (HepG2) were used for experiments. Lipid accumulation
      was examined by Filipin staining and intracellular cholesterol quantitative
      assay. The gene and protein expression of molecules involved in RAS and low
      density lipoprotein receptor (LDLr) pathway was examined by real-time PCR,
      immunofluorescent staining and Western blot. RESULTS: There was significantly
      increased expression of RAS components and extracellular matrix (ECM) in livers
      of high-fat-diet-fed apolipoprotein E gene-knockout mice compared with controls.
      Upregulation of RAS components was positively associated with increased plasma
      levels of lipid profile. The in vitro study further confirmed that cholesterol
      loading increased supernatant renin activity and Ang II level of HepG2 cells,
      accompanied by increased ECM production that was positively associated with
      increased expression of intracellular RAS components. Interestingly, Ang II
      treatment increased lipid accumulation in livers of C57BL/6 mice and HepG2 cells.
      Furthermore, Ang II treatment increased gene and protein expression of sterol
      regulatory element-binding protein (SREBP) cleavage activating protein (SCAP),
      SREBP-2 and LDLr, which were mediated by enhanced SCAP/SREBP-2 complex
      translocation from endoplasmic reticulum to Golgi. However, LDLr pathway was
      accordingly downregulated in livers of AT1 gene-knockout C57BL/6 mice or in HepG2
      cells treated by telmisartan. CONCLUSION: These findings demonstrate that lipid
      disorder and intrahepatic RAS activation synergistically accelerate NAFLD
      progression.

PMID- 27028411
TI  - A mild hand cleanser, alkyl ether sulphate supplemented with alkyl ether
      carboxylic acid and alkyl glucoside, improves eczema on the hand and prevents the
      growth of Staphylococcus aureus on the skin surface.
AB  - OBJECTIVE: Washing the hands using cleansers with antiseptic materials is the
      most popular method for hand hygiene and helps maintain health by preventing food
      poisoning and bacterial infections. However, repeated hand washing tends to
      induce eczema of the hand, such as dryness, cracking and erythema. Moreover,
      eczema on the hand leads to increased levels in Staphylococcus aureus (S. aureus)
      on the skin surface in contrast to expectations. Thus, mild hand cleansers which
      induce less eczema even with repeated washings are desired. Here, we evaluated
      the efficacy of a hand cleanser formulated with alkyl ether sulphate (AES), alkyl
      ether carboxylic acid (AEC) and alkyl glucoside (AG) that contains isopropyl
      methylphenol (IPMP) on skin symptoms and S. aureus levels. METHODS: Eczema of the
      hand and the presence of S. aureus on the skin surface were analysed prior to and
      following 4 weeks of usage of the hand cleanser. A soap-based hand cleanser with
      IPMP was used as a reference cleanser. Eczema and cutaneous conditions were
      evaluated by visual grading, transepidermal water loss (TEWL), stratum corneum
      moisture-retention ability (MRA) and skin surface pH. RESULTS: The repeated use
      of the soap-based hand cleanser significantly worsened the hand dryness, scaling
      and cracks on the tips of the fingers and significantly increased the TEWL and
      decreased the MRA. In contrast, usage of the test cleanser only induced a
      significant increase in skin dryness but did not induce skin scaling or cracking
      and did not increase TEWL or decrease the MRA. Corresponding to these changes in
      skin symptoms, the presence of S. aureus increased the following use of the
      reference cleanser but not the test cleanser. There was no significant difference
      in skin surface pH between the two cleansers. Moreover, the increase in S. aureus
      was significantly correlated to the worsening of skin dryness and scaling.
      CONCLUSION: These results suggest that not only antimicrobial activity but also
      the mildness, which minimizes cutaneous effects, are important for hand cleansers
      to prevent the growth of S. aureus. The cleanser formulated with AES, AEC and AG
      containing IPMP is mild and is effective to promote hand hygiene.

PMID- 27028412
TI  - Identification of four novel RHD alleles with altered expression of D in
      Brazilians.

PMID- 27028413
TI  - Combined Optical and Chemical Control of a Microsized Photofueled Janus Particle.
AB  - A Au-silica Janus particle is elevated along the laser beam axis in an optical
      trap. The propulsion mechanism is based on the local temperature gradient created
      around the particle due to the photothermal conversion of the gold-coated
      hemisphere. The height of the particle and its motion-direction are tuned by the
      nature and the concentration of the electrolytes in the medium. 

PMID- 27028414
TI  - Inflammatory myofibroblastic tumor of carotid artery resulting in recurrent
      syncope: A case report.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor rarely occurs in the carotid
      artery, whereas syncope is infrequently associated with neck mass. METHODS AND
      RESULTS: We reby present a case in which a 56-year-old man with inflammatory
      myofibroblastic tumor at the left carotid bifurcation and is accompanied by
      recurrent syncope and falls. He underwent surgery, after which corticosteroids
      and antibiotics were administered for a short term. No recurrence was observed
      during the 2-year follow-up. CONCLUSION: To our knowledge, this is the first case
      of inflammatory myofibroblastic tumor in which recurrent syncope is the only
      clinical manifestation. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2461
      E2463, 2016.

PMID- 27028415
TI  - Bacterial endophytes of Trans-Ili Alatau region's plants as promising components
      of a microbial preparation for agricultural use.
AB  - In this study, 382 isolates of bacterial endophytes from tissues of plants grown
      in the foothills and piedmont plains of the Trans-Ili Alatau were isolated. It
      was found that certain strains actively produce indole-3-acetic acid (IAA) in a
      medium containing l-tryptophan. Among the strains studied, 26 strains (66%)
      showed a positive response to production of IAA. Bacteria synthesized IAA in the
      range of 18.6 +/- 1.1 to 82.4 +/- 2.3 ug/ml. IAA was synthesized more actively by
      Streptosporangium sp. KK1 (44.1 ug/ml), Rhodococcus sp. KK 2 (42.5 ug/ml),
      Streptomyces tendae KK3 (44.9 ug/ml) strains. The most active auxin's producer is
      a Jeotgalicoccus halotolerans BAK1 strain, whose total level of IAA production
      reached 82.4 ug/ml. Such strains as Streptomyces griseorubiginosis KK4,
      Streptomyces sp. KK5 and Jeotgalicoccus halotolerans BAK1 were found to have a
      significant stimulating effect which was reflected in the increase of the length
      of the roots of soybean and barley. As a result, 8 promising strains with
      fungicidal, growth-stimulating, phosphorus dissolving and enzymatic activities
      were selected for the further development of highly microbiological preparations
      for crop research. 

PMID- 27028416
TI  - Transthyretin-related familial amyloidotic polyneuropathy found with abnormal
      urinalysis at a general health checkup.

PMID- 27028417
TI  - Efficacy of bariatric surgery in the treatment of severe obesity with proteinuria
      in a kidney transplant recipient.

PMID- 27028419
TI  - Corrigendum.

PMID- 27028418
TI  - Scenario of assessment might influence results using self-report frailty
      instrument in chronic dialysis patients.

PMID- 27028420
TI  - Corrigendum.

PMID- 27028421
TI  - Reagents for Storage and Regeneration of Nonstabilized Azomethine Ylides:
      Spiroanthraceneoxazolidines.
AB  - Nonstabilized azomethine ylides are easily trapped by anthraquinone to form
      stable spiro-oxazolidines, which have an unusual ability to undergo a
      cycloreversion in the presence of other dipolarophiles at 120-150  degrees C. All
      tested recycloadditions with carbonyl compounds and electron-poor alkenes
      occurred in moderate to high yields (41-92%). Moreover, increasing the reaction
      temperature to 210  degrees C made it possible to obtain adducts with low
      reactive dipolarophiles. 

PMID- 27028422
TI  - We cannot ignore bias, especially if effects are small, but we need better
      methods for evaluating prevention systems.

PMID- 27028423
TI  - Translational Dynamics of Lipidated Ras Proteins in the Presence of Crowding
      Agents and Compatible Osmolytes.
AB  - Ras proteins are small GTPases and are involved in transmitting signals that
      control cell growth, differentiation, and proliferation. Since the cell cytoplasm
      is crowded with different macromolecules, understanding the translational
      dynamics of Ras proteins in crowded environments is crucial to yielding deeper
      insight into their reactivity and function. Herein, the translational dynamics of
      lipidated N-Ras and K-Ras4B is studied in the bulk and in the presence of a
      macromolecular crowder (Ficoll) and the compatible osmolyte and microcrowder
      sucrose by fluorescence correlation spectroscopy. The results reveal that N-Ras
      forms dimers due to the presence of its lipid moiety in the hypervariable region,
      whereas K-Ras4B remains in its monomeric form in the bulk. Addition of a
      macromolecular crowding agent gradually favors clustering of the Ras proteins. In
      20 wt % Ficoll N-Ras forms trimers and K-Ras4B dimers. Concentrations of sucrose
      up to 10 wt % foster formation of N-Ras trimers and K-Ras dimers as well. The
      results can be rationalized in terms of the excluded-volume effect, which
      enhances the association of the proteins, and, for the higher concentrations, by
      limited-hydration conditions. The results of this study shed new light on the
      association state of these proteins in a crowded environment. This is of
      particular interest for the Ras proteins, because their solution state-monomeric
      or clustered-influences their membrane-partitioning behavior and their interplay
      with cytosolic interaction partners. 

PMID- 27028424
TI  - Telomerase reactivation in cancers: Mechanisms that govern transcriptional
      activation of the wild-type vs. mutant TERT promoters.
AB  - Transcriptional activation of telomerase reverse transcriptase (TERT) gene is a
      rate-limiting determinant in the reactivation of telomerase expression in
      cancers. TERT promoter mutations represent one of the fundamental mechanisms of
      TERT reactivation in cancer development. We review recent studies that elucidate
      the molecular mechanisms underscoring activation of mutant TERT promoters.

PMID- 27028425
TI  - Drospirenone as estrogen-free pill and hemostasis: coagulatory study results
      comparing a novel 4 mg formulation in a 24 + 4 cycle with desogestrel 75 MUg per
      day.
AB  - INTRODUCTION: A novel estrogen free contraceptive pill, with drospirenone 4 mg in
      a dosing regimen of 24 + 4, has been developed with a pearl-index of 0.51 (95% CI
      0.1054; 1.4922). The aim of the following study was to determine if 4 mg DRSP has
      an impact on coagulation factors and thrombotic risks in comparison with
      desogestrel 75 MUg. PATIENTS AND METHODS: Thirty-nine patients received 4 mg DRSP
      24 + 4 d and 29 desogestrel 75 MUg per day continuously during nine complete
      cycles. Following hemostatic parameters were evaluated: Apc resistance,
      Antithrombin III, Protein C reactivity, Factor VII, Factor VIII, and d-Dimer.
      RESULTS: Factor VII decreased from 1.123 to 1.066 in the DRSP group and from
      1.241 to 1.034 in the desogestrel group (p = 0.0088). The difference in change of
      mean Protein C activity from baseline to endpoint was -0.0332 in the DRSP versus 
      0.157 in the desogestrel group (p = 0.0249). d-Dimer values dropped in the DRSP
      group from baseline values of 264.9-215.0 ng/mL, whereas in the desogestrel group
      there was a rise from 201.4 ng/mL to 281.5 ng/mL. DISCUSSION: DRSP 4 mg was not
      associated with any meaningful changes on hemostatic parameters, indicating a
      lack of effect on hemostasis.

PMID- 27028426
TI  - Simple ellipsoid reconstruction technique for a hypoplastic portal vein during
      pediatric liver transplantation.

PMID- 27028427
TI  - Eosinophilic pustular folliculitis: A proposal of diagnostic and therapeutic
      algorithms.
AB  - Eosinophilic pustular folliculitis (EPF) is a sterile inflammatory dermatosis of
      unknown etiology. In addition to classic EPF, which affects otherwise healthy
      individuals, an immunocompromised state can cause immunosuppression-associated
      EPF (IS-EPF), which may be referred to dermatologists in inpatient services for
      assessments. Infancy-associated EPF (I-EPF) is the least characterized subtype,
      being observed mainly in non-Japanese infants. Diagnosis of EPF is challenging
      because its lesions mimic those of other common diseases, such as acne and
      dermatomycosis. Furthermore, there is no consensus regarding the treatment for
      each subtype of EPF. Here, we created procedure algorithms that facilitate the
      diagnosis and selection of therapeutic options on the basis of published work
      available in the public domain. Our diagnostic algorithm comprised a simple
      flowchart to direct physicians toward proper diagnosis. Recommended regimens were
      summarized in an easy-to-comprehend therapeutic algorithm for each subtype of
      EPF. These algorithms would facilitate the diagnostic and therapeutic procedure
      of EPF.

PMID- 27028428
TI  - Identification of Biological and Pharmaceutical Mast Cell- and Basophil-Related
      Targets.

PMID- 27028431
TI  - RESULTS OF SURGICAL TREATMENT OF DENERATIVE ARTHROPATHY OF THE ROTATOR CUFF USING
      HEMIARTHROPLASTY- CTA((r)).
AB  - OBJECTIVE: To assess results of CTA((r)) partial shoulder arthroplasty for
      treatment of degenerative arthropathy of the rotator cuff. METHODS: Between
      December 2006 and June 2009, 23 shoulders of 23 patients were submitted to
      CTA((r)) type partial shoulder arthroplasty for treatment of arthropathy
      secondary to rotator cuff injury. Post-operative follow up time ranged from 6 to
      35 months. Mean age was 74.1 years. Patients were predominantly female,
      representing 78.3% of cases. The right limb was affected in 18 patients. All
      patients had undergone at least 6 months of physiotherapy without improvement of
      the algetic picture, and being submitted to surgery by the same surgical team.
      None of the patients had history of surgery on the affected shoulder. The method
      elected for assessing patients during post-operative follow up was based on UCLA
      scoring criteria. RESULTS: Improvement in pain was observed in all patients after
      arthroplasty. Mean UCLA pain score was 9.22 (ranging from 10 to 8). Mean function
      was 6 (10 to 2). Active frontal flexion was 2.39 (highest score 4 and lowest 0).
      Mean frontal flexion force was 4.09, maximum was 5 and minimum 3. Mean score on
      the UCLA was 26.52. 95% were satisfied with the surgery. CONCLUSION: CTA((r))
      type partial shoulder arthroplasty produced satisfactory results in the treatment
      of degenerative arthropathy of the rotator cuff and had a low rate of
      complications.

PMID- 27028432
TI  - Accuracy of Patient and Care Partner Identification of Cognitive Impairments in
      Parkinson's Disease-Mild Cognitive Impairment.
AB  - BACKGROUND: Criteria for Parkinson's disease-mild cognitive impairment require a
      caregiver or patient complaint or clinician observation of cognitive decline and
      objective evidence of cognitive deficit in at least 1 of 5 cognitive domains.
      This study examines the accuracy of Parkinson's disease-mild cognitive impairment
      patient and care partner reports of specific cognitive difficulties. METHODS: A
      total of 42 Parkinson's disease-mild cognitive impairment patients and their care
      partners reported the absence or presence of deficits in each cognitive domain
      during an interview. A deficit in each domain was defined by scores <= 1.5
      standard deviations below the mean on corresponding cognitive tests. RESULTS:
      Sensitivity, specificity, and positive and negative predictive values were modest
      for patient and care partner reports across all domains. Patients' and care
      partners' accuracy in observing objectively identified deficits was poor across
      all domains (<= 60% agreement; kappa <= .07). Patient and care partner reports
      showed moderate agreement in all domains except attention (>= 74% agreement;
      kappa >= .43). CONCLUSIONS: Parkinson's disease-mild cognitive impairment
      patients and their care partners may not be accurate in identifying specific
      cognitive deficits. Thus, even patients (and care partners) who correctly report
      having a cognitive deficit may misidentify the specific deficit. The finding
      supports the value of International Parkinson and Movement Disorder Society
      Parkinson's disease-Mild Cognitive Impairment Level II assessment and cautions
      against relying on subjective report or screening in research in which the nature
      of cognitive deficit identification or treatment is paramount. Overreliance on
      patient and care partner reports of specific impairments may distort
      epidemiologic estimates of mild cognitive impairment subtypes and misdirect
      cognitive rehabilitation at incorrect domains. (c) 2016 International Parkinson
      and Movement Disorder Society.

PMID- 27028433
TI  - Defensive Traits in Young Pine Trees Cluster into Two Divergent Syndromes Related
      to Early Growth Rate.
AB  - The combination of defensive traits leads to the evolution of 'plant defense
      syndromes' which should provide better protection against herbivores than
      individual traits on their own. Defense syndromes can be generally driven by
      plant phylogeny and/or biotic and abiotic factors. However, we lack a solid
      understanding of (i) the relative importance of shared evolution vs. convergence
      due to similar ecological conditions and (ii) the role of induced defense
      strategies in shaping defense syndromes. We investigate the relative roles of
      evolutionary and ecological factors shaping the deployment of pine defense
      syndromes including multiple constitutive and induced chemical defense traits. We
      performed a greenhouse experiment with seedlings of eighteen species of Pinaceae
      family, and measured plant growth rate, constitutive chemical defenses and their
      inducibility. Plant growth rate, but not phylogenetic relatedness, determined the
      deployment of two divergent syndromes. Slow-growing pine species living in harsh
      environments where tissue replacement is costly allocated more to constitutive
      defenses (energetically more costly to produce than induced). In contrast, fast
      growing species living in resource-rich habitats had greater inducibility of
      their defenses, consistent with the theory of constitutive-induced defense trade
      offs. This study contributes to a better understanding of evolutionary and
      ecological factors driving the deployment of defense syndromes. 

PMID- 27028435
TI  - Opportunities for the Cardiovascular Community in the Precision Medicine
      Initiative.
AB  - The Precision Medicine Initiative recently announced by President Barack Obama
      seeks to move the field of precision medicine more rapidly into clinical care.
      Precision medicine revolves around the concept of integrating individual-level
      data including genomics, biomarkers, lifestyle and other environmental factors,
      wearable device physiological data, and information from electronic health
      records to ultimately provide better clinical care to individual patients. The
      Precision Medicine Initiative as currently structured will primarily fund efforts
      in cancer genomics with longer-term goals of advancing precision medicine to all
      areas of health, and will be supported through creation of a 1 million person
      cohort study across the United States. This focused effort on precision medicine
      provides scientists, clinicians, and patients within the cardiovascular community
      an opportunity to work together boldly to advance clinical care; the community
      needs to be aware and engaged in the process as it progresses. This article
      provides a framework for potential involvement of the cardiovascular community in
      the Precision Medicine Initiative, while highlighting significant challenges for
      its successful implementation. 

PMID- 27028436
TI  - ECG Response: January 12, 2016.

PMID- 27028434
TI  - Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in
      Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age:
      The CARDIA Study.
AB  - BACKGROUND: We explored whether, the Pathobiological Determinants of
      Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18
      to 30 years of age and changes in these scores would more strongly predict
      coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25
      years later, than scores measured 25 years later. METHODS AND RESULTS: In the
      Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008
      participants had measurements of risk score components at 5-year intervals
      beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years
      of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher
      score and c-statistics for predicting CAC/AAC were calculated. The prevalence of
      CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC
      were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence
      interval [CI], 1.25-1.33 versus OR, 1.12; 95% CI, 1.11-1.14). For AAC, ORs at
      years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24-1.34 versus OR, 1.22; 95% CI,
      1.19-1.26). C-statistic for CAC prediction was higher at year 0 than year 25
      (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670).
      ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10.
      Including change in PDAY scores with baseline scores improved prediction.
      CONCLUSIONS: Atherosclerosis risk and change in risk assessed in young adulthood
      years before subclinical atherosclerosis imaging provide strong prediction of
      future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in
      addition to risk measured at the time of study.

PMID- 27028437
TI  - A Rare Case of Acquired Thoracic Aortic Coarctation Treated Medically.

PMID- 27028438
TI  - Descending Aorta Rupture During Transcatheter Aortic Valve Replacement.

PMID- 27028439
TI  - Cardiology Patient Pages: Antidotes for Bleeding Caused by Novel Oral
      Anticoagulants.

PMID- 27028440
TI  - Letter by Barik Regarding Article, "Now You See It, Now You Don't?".

PMID- 27028441
TI  - Letter by Philip Regarding Articles, "Clinical and Hemodynamic Outcomes up to 7
      Years After Transcatheter Pulmonary Valve Replacement in the US Melody Valve
      Investigational Device Exemption Trial" and "Pediatric Transcatheter Valve
      Replacement: Guests at Our Own Table?".

PMID- 27028442
TI  - Letter by Sipido and Glanzel Regarding Article, "Poorly Cited Articles in Peer
      Reviewed Cardiovascular Journals from 1997 to 2007: Analysis of 5-Year Citation
      Rates".

PMID- 27028443
TI  - Response to Letter Regarding Article, "Poorly Cited Articles in Peer-Reviewed
      Cardiovascular Journals from 1997 to 2007: Analysis of 5-Year Citation Rates".

PMID- 27028444
TI  - Environmental effects and individual body condition drive seasonal fecundity of
      rabbits: identifying acute and lagged processes.
AB  - The reproduction of many species is determined by seasonally-driven resource
      supply. But it is difficult to quantify whether the fecundity is sensitive to
      short- or long-term exposure to environmental conditions such as rainfall that
      drive resource supply. Using 25 years of data on individual fecundity of European
      female rabbits, Oryctolagus cuniculus, from semiarid Australia, we investigate
      the role of individual body condition, rainfall and temperature as drivers of
      seasonal and long-term and population-level changes in fecundity (breeding
      probability, ovulation rate, embryo survival). We built distributed lag models in
      a hierarchical Bayesian framework to account for both immediate and time-lagged
      effects of climate and other environmental drivers, and possible shifts in
      reproduction over consecutive seasons. We show that rainfall during summer, when
      rabbits typically breed only rarely, increased breeding probability immediately
      and with time lags of up to 10 weeks. However, an earlier onset of the yearly
      breeding period did not result in more overall reproductive output. Better body
      condition was associated with an earlier onset of breeding and higher embryo
      survival. Breeding probability in the main breeding season declined with
      increased breeding activity in the preceding season and only individuals in good
      body condition were able to breed late in the season. Higher temperatures reduce
      breeding success across seasons. We conclude that a better understanding of
      seasonal dynamics and plasticity (and their interplay) in reproduction will
      provide crucial insights into how lagomorphs are likely to respond and
      potentially adapt to the influence of future climate and other environmental
      change.

PMID- 27028445
TI  - Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus
      Warfarin Alone in Mechanical Valve Prostheses.
AB  - BACKGROUND: The use of combined therapy of antiplatelet and anticoagulant versus
      anticoagulant alone to reduce instances of thromboembolic events in patients with
      heart valve prostheses is an established standard of care in many countries but
      not in Egypt. A previous Markov model cost-effectiveness study on Egyptian
      patients aged 50-60 years demonstrated that the combined therapy reduces the
      overall treatment cost. However, due to the lack of actual real-world data on
      cost-effectiveness and the limitation of the Markov model study to 50- to 60-year
      old patients, the Egyptian medical community is still questioning whether the
      added benefit is worth the cost. OBJECTIVE: To assess, from the perspective of
      the Egyptian health sector, the cost-effectiveness of the combined use of
      warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients
      with mechanical heart valve prostheses who began therapy between the age of 15
      and 50 years. METHODS: An economic evaluation was conducted alongside a
      randomized, controlled trial to assess the cost-effectiveness of the combined
      therapy in patients with mechanical valve prostheses. A total of 316 patients
      aged between 15 and 50 years were included in the study and randomly assigned to
      a group treated with both warfarin and aspirin or a group treated with warfarin
      alone. RESULTS: The patients in the combined therapy group exhibited a
      significantly longer duration of protection against the first event. Fewer
      primary events were observed in the patients treated with warfarin plus aspirin
      than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a
      higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained
      for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013
      0.118), although this difference did not reach a conventional level of
      statistical significance. The total costs over a 4-year period were lower with
      the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which
      yielded an incremental cost-effectiveness ratio of -US$4206 per QALY gained.
      Thus, the combined therapy was dominant. All costs were reported in US dollars
      (USD) for the financial year 2014. CONCLUSIONS: The results of this analysis
      indicate that from the perspective of the Egyptian health sector, the addition of
      aspirin to the typical warfarin therapy is more effective and less costly for
      patients with mechanical valve prostheses than treatment with warfarin alone.
      This combined strategy could be adopted to prevent the complications of
      mechanical valve prostheses. Our study adds to the body of evidence supporting
      the option of warfarin-plus-aspirin therapy for patients with mechanical valve
      prostheses.

PMID- 27028447
TI  - Response to the Commentary of Naldi and Cazzaniga Entitled 'Are All Screening
      Programmes Created Equal? The Case of Melanoma'.

PMID- 27028446
TI  - Shared Physiological Traits of Exophiala Species in Cold-Blooded Vertebrates, as
      Opportunistic Black Yeasts.
AB  - Several species of the genus Exophiala are found as opportunistic pathogens on
      humans, while others cause infections in cold-blooded waterborne vertebrates.
      Opportunism of these fungi thus is likely to be multifactorial. Ecological traits
      [thermotolerance and pH tolerance, laccase activity, assimilation of mineral oil,
      and decolorization of Remazol Brilliant Blue R (RBBR)] were studied in a set of
      40 strains of mesophilic Exophiala species focused on the salmonis-clade mainly
      containing waterborne species. Thermophilic species and waterborne species
      outside the salmonis-clade were included for comparison. Strains were able to
      tolerate a wide range of pHs, although optimal growth was observed between pH 4.0
      and 5.5. All strains tested were laccase positive. Strains were able to grow in
      the presence of the compounds (mineral oil and RBBR) with some differences in
      assimilation patterns between strains tested and also were capable of degrading
      the main chromophore of RBBR. The study revealed that distantly related
      mesophilic species behave similarly, and no particular trend in evolutionary
      adaptation was observed. 

PMID- 27028448
TI  - The Gut Bacteria-Driven Obesity Development.
AB  - It is now well established that a healthy gut flora is largely responsible for
      the overall health of the host, while a perturbation in gut microbial communities
      can contribute to disease susceptibility. Obesity is a complex process involving
      genetic and environmental factors with an epidemiological burden that makes it a
      major public health issue. Studies of germ-free or gnotobiotic mice provided
      evidence that the diversity, as well as the presence and relative proportion of
      different microbes in the gut play active roles in energy homeostasis. Similarly,
      human studies showed that both the diversity of the microbiota and the
      Bacteroidetes/Firmicutes ratio are decreased in obese individuals. The 'obese
      microbiota' seems to be able to increase dietary energy harvest and favor weight
      gain and fat deposition. Although research in this field has just started and
      many of the available data are still conflicting, the results are providing
      exciting perspectives, and gut microbiota manipulation has already become a new
      target for both prevention and treatment of obesity. 

PMID- 27028449
TI  - Preoperative anxiety may increase postcesarean delivery pain and analgesic
      consumption.
AB  - BACKGROUND: The aim of this study was to reveal the relationship between high
      level of prenatal anxiety and postoperative pain and/or analgesic consumption in
      women undergoing elective cesarean delivery under spinal anesthesia. METHODS:
      Eighty women, aged between 18-45 years with minimum 37 week- gestation and
      received spinal anesthesia during elective cesarean delivery, were included into
      this observational cohort study. Prenatal anxiety was measured with state anxiety
      inventory, trait anxiety inventory and somatosensory amplification scale. Visual
      Analogue Scale (VAS) was used to quantify postoperative pain. Amount of analgesic
      consumed was recorded at 6th, 12th and 18th postoperative hours. RESULTS: State
      Anxiety Score was above the threshold level (>45) in 18 women (22.5%). No
      difference was found between women with and without high state anxiety scores
      except for significantly higher BMI values in high-score group (P=0.07). In
      multivariate analysis, high BMI at pregnancy (OR: 1.2, 95% CI; 1.0-1.5, P=0.02)
      and high State Anxiety Score (OR: 1.1, 95% CI; 1.0-1.2, P=0.01) emerged as
      independent predictors of higher mean pain scores (VAS >4 cm) within 18 hours
      after cesarean delivery. Also, high State Anxiety Score was found to be
      independently associated with higher pethidine consumption after cesarean
      delivery (OR: 1.1, 95% CI; 1.0-1.2, P=0.006). CONCLUSIONS: State anxiety has a
      negative effect on postcesarean pain whereas trait anxiety does not seem to
      produce such effect. The effect seems to be more profound in overweight women.
      Detection of anxiety level before elective cesarean delivery and therapeutic
      approach to pregnant women may be useful for postoperative pain control.

PMID- 27028450
TI  - Serious renal and urological complications in fast-track primary total hip and
      knee arthroplasty; a detailed observational cohort study.
AB  - BACKGROUND: Overall medical complications have been reduced after fast-track
      total hip (THA) and knee arthroplasty (TKA), but data on specific renal and
      urological (RU) complications are limited. METHODS: To describe the incidence and
      consequences of serious RU complications resulting in length of stay > 4 days or
      30-day readmissions after fast-track THA and TKA, we conducted a detailed
      observational study based upon prospectively collected pre-operative data and a
      complete 30-day follow-up on complications and re-admissions in a unselected
      cohort of 8,804 consecutive fast-track THAs and TKAs. Our main outcomes were
      incidence, types and consequences of RU complications. RESULTS: Of 8,804
      procedures, 54 (0.61%) developed serious RU complications resulting in 38 (0.43%)
      prolonged hospitalisations and 17 (0.19%) readmissions. Acute kidney injury
      (AKI), defined as an increase in serum creatinine by >= 0.3 mg/dl or >= 1.5 times
      baseline, accounted for complications (0.49%), and was most frequently associated
      with postoperative hypotension Of the AKI patients, 25 (58.1%) had a preoperative
      estimated glomerular filtration rate < 60 2 43 ml/min/1.73 m and 16 of these had
      received a NSAID postoperatively. Seven complications . (0.08 %) were urological,
      mainly haematuria after bladder catheterisation, whereas 5 (0.06 were
      urosepsis/pyelonephritis. CONCLUSION: The overall incidence of serious RU
      complications after fast-track THA and TKA was 0.61 %. AKI occurred in 0.49% and
      was most often due to pre-existing kidney disease and postoperative hypotension,
      calling for increased focus on perioperative fluid management and optimisation of
      the perioperative care of patients with pre-existing kidney disease.

PMID- 27028451
TI  - Point-of-care coagulation management algorithms during ECMO support: are we there
      yet?
AB  - Haemorrhagic and thromboembolic events are common and the main cause for
      morbidity and mortality in patients treated with extracorporeal membrane
      oxygenation (ECMO). Monitoring of an adequate anticoagulation is, therefore,
      essential in patients during ECMO therapy. This review aims to describe the
      current evidence and emerging data relating to anticoagulation therapy and point
      of-care (POC) coagulation monitoring in ECMO patients. Central laboratory-based
      coagulation testing including activated partial thromboplastin time (aPTT),
      international normalized ratio (INR) of the prothrombin time (PT), and activated
      clotting time (ACT) is most commonly used for coagulation monitoring. Several
      lines of coagulation monitoring devices have been explored for POC assessment of
      anticoagulation and/or haemostasis during ECMO. POC-type ACT, aPTT and PT have a
      shorter turn-around time, but they might exhibit a relevant bias in agreement
      with laboratory-based coagulation tests, and sensitivity and specificity for
      intervention are variable compared with laboratory- based tests. Whole-blood
      viscoelastic coagulation tests including ROTEM(r) and TEG(r) and platelet
      function testing have been increasingly used for monitoring haemostasis in ECMO
      patients. However, no single laboratory-based or POC coagulation test can
      reliably predict the emergence of haemorrhagic or thrombotic events. Further,
      treatment algorithms based on POC testing are scarce for ECMO patients. Larger
      prospective studies are necessary to evaluate the usefulness of POC coagulation
      monitors or a combination of them in potentially improving anticoagulation and
      decreasing haemorrhagic and thromboembolic complications.

PMID- 27028452
TI  - High-flow oxygen therapy in hypoxemic respiratory failure: insights from the
      FLORALI trial.

PMID- 27028453
TI  - Structure elucidation and NMR assignments of daldinone E and rickenyl F from the
      fungus Hypoxylon sp. DWS T-P-6.

PMID- 27028454
TI  - Surgical procedures in patients with haemophilic arthropathy of the ankle.
AB  - BACKGROUND: In haemophilia, the ankle joint is one of the most common and
      earliest joints affected by recurrent bleeding, commonly resulting in end-stage
      ankle osteoarthritis during early adulthood. The surgical treatment of
      haemophilic ankle arthropathy is challenging. PURPOSE: This review aims to
      highlight the literature addressing clinical outcomes following the most common
      approaches for different stages of haemophilia-induced ankle osteoarthritis:
      arthroscopic debridement, joint distraction arthroplasty, supramalleolar
      osteotomies, total ankle replacement, and ankle arthrodesis. METHODS: A
      systematic literature review was performed using established medical literature
      databases. The following information was retrieved from the literature: patients'
      demographics, surgical technique, duration of follow-up, clinical outcome
      including pain relief and complication rate. RESULTS: A total of 42 clinical
      studies published between 1978 and 2015 were included in the systematic
      literature review. Eight and 34 studies had prospective and retrospective design,
      respectively. The most common studies were level IV studies (64.3%). DISCUSSION:
      The orthopaedic treatment of patients with haemophilic ankle osteoarthritis is
      often challenging and requires complete and careful preoperative assessment. In
      general, both joint-preserving and joint non-preserving procedure types can be
      performed. All specific relative and absolute contraindications should be
      considered to achieve appropriate postoperative outcomes. CONCLUSION: The current
      literature demonstrated that orthopaedic surgeries, with appropriate indication,
      in patients with haemophilic ankle arthropathy result in good postoperative
      results comparable to those observed in non-haemophiliacs. The surgical treatment
      should be performed in a setting with the ability to have multidisciplinary
      management, including expertise in haematology.

PMID- 27028455
TI  - Men's use of sexual health and HIV services in Swaziland: a mixed methods study.
AB  - BACKGROUND: Over one-quarter of the adult population in Swaziland is estimated to
      be HIV positive. Men's use of sexual health (SH) services has significant
      implications for HIV prevention. This study aimed to understand Swazi men's
      health-seeking behaviours in relation to SH and HIV services. METHODS: A
      household survey was conducted in Manzini (n=503), complemented by 23 semi
      structured interviews and two focus group discussions (with a total of 10
      participants). RESULTS: One-third of male survey participants used SH services in
      the past year, most commonly HIV testing (28%). Service users were more likely to
      be sexually active (aOR 3.21, 95% CI: 1.81-5.68 for those with one partner; and
      aOR 2.35, 95% CI: 1.25-4.41 for those with multiple partners) compared with
      service non-users. Service users were less likely to prefer HIV services to be
      separated from other healthcare services (aOR 0.50, 95% CI: 0.35-0.71), or to
      agree with travelling further for their HIV test (aOR 0.52, 95% CI: 0.33-0.82)
      compared with non-users, after controlling for age-group and education. Men
      avoided SH services because they feared being stigmatised by STI/HIV testing, are
      uncomfortable disclosing SH problems to female healthcare providers, and avoided
      HIV testing by relying on their wife's results as a proxy for their own status.
      Informal providers, such as traditional healers, were often preferred because
      practitioners were more often male, physical exams were not required and
      appointments and payment options were flexible. CONCLUSION: To improve men's
      uptake of SH services, providers and services need to be more sensitive to men's
      privacy concerns, time restrictions and the potential stigma associated with
      STI/HIV testing.

PMID- 27028456
TI  - The Effectiveness of Aripiprazole for Tics, Social Adjustment, and Parental
      Stress in Children and Adolescents with Tourette's Disorder.
AB  - OBJECTIVE: Tourette's syndrome (TS) frequently results in a negative impact on
      multiple functional domains. This prospective open-label study investigated the
      potential effectiveness of aripiprazole for tics, social adjustment, and parental
      stress in children and adolescents with TS. METHODS: Study participants consisted
      of 26 patients (mean age 10.4 +/- 3.0 years; 22 boys and 4 girls) who were
      prescribed aripiprazole, with each dose ranging from 2.5 to 15 mg/day. At
      baseline and 2, 4, and 8 weeks from baseline, tic symptoms, social adjustment,
      and parenting stress were assessed using the Yale Global Tic Severity Scale
      (YGTSS), the Social Adjustment Inventory for Children and Adolescents (SAICA),
      and the Parenting Stress Index (PSI). Aripiprazole could be optionally titrated
      from 2.5 to 30 mg/day at each visit. RESULTS: Of the 26 patients at the initial
      visit, 22 (84.6%) completed the study. The mean dose of aripiprazole at the
      endpoint was 8.0 +/- 4.0 mg/day. During the 8-week aripiprazole treatment period,
      motor tics, phonic tics, and impairment on the YGTSS all showed significant
      improvement. Home behaviors on the SAICA and child domain on the PSI also showed
      significant improvement. Patients' phonic tics, but not motor tics, showed a
      positive correlation with their school function and peer relationships. The child
      domain on the PSI was positively correlated with motor tics, phonic tics, and
      impairment, as measured by the YGTSS. CONCLUSIONS: An 8-week aripiprazole
      treatment program for children and adolescents with TS was beneficial to their
      tic symptoms, behaviors at home, and caregivers' stress with regard to fulfilling
      parenting roles. A long-term placebo-controlled trial with larger samples is
      warranted to confirm the effectiveness of aripiprazole for social adjustment and
      parental stress.

PMID- 27028457
TI  - Correction of the Pathogenic Alternative Splicing, Caused by the Common GNB3
      c.825C>T Allele, Using a Novel, Antisense Morpholino.
AB  - The very common GNB3 c.825C>T polymorphism (rs5443) is present in approximately
      half of all human chromosomes. Significantly, the presence of the GNB3 825T
      allele has been strongly associated with predisposition to essential
      hypertension. Paradoxically the presence of the GNB3 825T allele, in exon 10,
      introduces a pathogenic alternative RNA splice site into the middle of exon 9. To
      attempt to correct this pathogenic aberrant splicing, we, therefore,
      bioinformatically designed, using a Gene Tools((r)) algorithm, a GNB3-specific,
      antisense morpholino. It was hoped that this morpholino would behave in vitro as
      either a potential splice blocker and/or exon skipper, to both bind and
      inhibit/reduce the aberrant splicing of the GNB3 825T allele. On transfecting a
      human lymphoblast cell line homozygous for the 825T allele, with this antisense
      morpholino, we encouragingly observed both a significant reduction (from ~58% to
      ~5%) in the production of the aberrant smaller GNB3 transcript, and a subsequent
      increase in the normal GNB3 transcript (from ~42% to ~95%). Our results
      demonstrate the potential use of a GNB3-specific antisense morpholino, as a
      pharmacogenetic therapy for essential hypertension.

PMID- 27028458
TI  - Transparent Films from CO2 -Based Polyunsaturated Poly(ether carbonate)s: A Novel
      Synthesis Strategy and Fast Curing.
AB  - Transparent films were prepared by cross-linking polyunsaturated poly(ether
      carbonate)s obtained by the multicomponent polymerization of CO2 , propylene
      oxide, maleic anhydride, and allyl glycidyl ether. Poly(ether carbonate)s with
      ABXBA multiblock structures were obtained by sequential addition of mixtures of
      propylene oxide/maleic anhydride and propylene oxide/allyl glycidyl ether during
      the polymerization. The simultaneous addition of both monomer mixtures provided
      poly(ether carbonate)s with AXA triblock structures. Both types of
      polyunsaturated poly(ether carbonate)s are characterized by diverse functional
      groups, that is, terminal hydroxy groups, maleate moieties along the polymer
      backbone, and pendant allyl groups that allow for versatile polymer chemistry.
      The combination of double bonds substituted with electron-acceptor and electron
      donor groups enables particularly facile UV- or redox-initiated free-radical
      curing. The resulting materials are transparent and highly interesting for
      coating applications.

PMID- 27028459
TI  - Drug-drug interactions between moxifloxacin and rifampicin based on
      pharmacokinetics in vivo in rats.
AB  - Moxifloxacin and rifampicin are all the first-line options for the treatment of
      active tuberculosis, which are often combined for the treatment of multidrug
      resistance pulmonary tuberculosis in clinic. However, the potential drug-drug
      interactions between moxifloxacin and rifampicin were unknown. The aim of this
      study was to investigate the drug-drug interactions between moxifloxacin and
      rifampicin based on their pharmacokinetics in vivo after oral administration of
      the single drug and both drugs, and reveal their mutual effects on their
      pharmacokinetics. Eighteen male Sprague-Dawley rats were randomly assigned to
      three groups: moxifloxacin group, rifampicin group and moxifloxacin + rifampicin
      group. Plasma concentrations of moxifloxacin and rifampicin were determined using
      LC-MS at the designated time points after drug administration, and the main
      pharmacokinetic parameters were calculated. In addition, effects of moxifloxacin
      and rifampicin on their metabolic rate and absorption were investigated using rat
      liver microsome incubation systems and Caco-2 cell transwell model. The main
      pharmacokinetic parameters of moxifloxacin including Tmax , Cmax , t1/2 and AUC(0
      t) increased more in the moxifloxacin + rifampicin group than in the moxifloxacin
      group, but the difference was not significant (p > 0.05). However, the
      pharmacokinetic parameters of rifampicin, including peak concentration, area
      under the concentration-time curve, half-life and the area under the first moment
      plasma concentration-time curve, increased significantly (p < 0.05) compared with
      the rifampicin group, and the time to peak concentration decreased significantly
      (p < 0.05). The mean residence time of rifampicin also increased in moxifloxacin
      + rifampicin group compared with the rifampicin group, but the difference was not
      significant (p > 0.05). The rat liver microsome incubation experiment indicated
      that moxifloxacin could increase the metabolic rate of rifampicin from 23.7 to
      38.7 min. However, the Caco-2 cell transwell experiment showed that moxifloxacin
      could not affect the absorption rate of rifampicin. These changes could enhance
      the drug efficacy, but they could also cause drug accumulation, which might
      induce adverse effect, so it was suggested that the drug dosage should be
      adjusted and the drug concentration in plasma should be monitored if moxifloxacin
      and rifampicin are co-administered. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27028460
TI  - Hide-and-Seek: Narcissism and "Selfie"-Related Behavior.
AB  - While prior research has examined the relationship between narcissism and self
      promoting behaviors on social media (e.g., posting selfies), little is known
      about the extent to which individuals' level of narcissism relates to how
      involved they are in other people's feedback (e.g., comments and "likes")
      received on their selfies, or how observant and responsive they are to other
      people's selfie postings. The present study investigates how narcissism relates
      to such selfie-related behaviors, as well as overall evaluation of selfie-posting
      behavior and intention to post selfies in the future. By employing a total of 315
      Korean subjects who take and post selfies on social networking sites, the present
      study indicates that individuals higher in narcissism are more likely to evaluate
      selfie-posting behavior favorably, be involved in the feedback provided by
      others, and be observant of other people's selfies. However, level of narcissism
      did not moderate the relationship between how much one observes others' selfies
      and the likelihood of providing a comment or "like" on other people's selfies. 

PMID- 27028461
TI  - Analysis of the distances covered and technical actions performed by professional
      tennis players during official matches.
AB  - The purpose of this study was to analyse the physical and technical performances
      of professional tennis players during official matches. The trajectories of eight
      players were obtained during matches, using an automatic tracking method. The
      distances covered and technical performances were analysed for the first and
      second sets. The athletes covered (mean +/- standard deviation) a total of 1702.4
      +/- 448.2 m in the first set, 1457.6 +/- 678.1 m in the second set and 3160.0 +/-
      880.1 in the entire match. No differences were found between the sets for the
      physical variables (lateral and forward displacements, distance covered per
      rally, per game and per set, and the percentage of time spent in each range of
      velocity). However, the distances covered by the athletes during the rallies in
      which they were serving (median = 5.2; interquartile range (IQR) = 6.7 m) were
      statistically smaller than when they were returning (median = 6.2; IQR = 7.7 m).
      Forehand ground stroke proficiency decreased from the first (mean +/- standard
      deviation: 75.2 +/- 4.11%) to the second set (mean +/- standard deviation = 65.5
      +/- 14.3%). In conclusion, tennis players did not present reduced physical
      performance from the first to the second set.

PMID- 27028462
TI  - Classification of phytoplankton cells as live or dead using the vital stains
      fluorescein diacetate and 5-chloromethylfluorescein diacetate.
AB  - Regulations for ballast water treatment specify limits on the concentrations of
      living cells in discharge water. The vital stains fluorescein diacetate (FDA) and
      5-chloromethylfluorescein diacetate (CMFDA) in combination have been recommended
      for use in verification of ballast water treatment technology. We tested the
      effectiveness of FDA and CMFDA, singly and in combination, in discriminating
      between living and heat-killed populations of 24 species of phytoplankton from
      seven divisions, verifying with quantitative growth assays that uniformly live
      and dead populations were compared. The diagnostic signal, per-cell fluorescence
      intensity, was measured by flow cytometry and alternate discriminatory thresholds
      were defined statistically from the frequency distributions of the dead or living
      cells. Species were clustered by staining patterns: for four species, the
      staining of live versus dead cells was distinct, and live-dead classification was
      essentially error free. But overlap between the frequency distributions of living
      and heat-killed cells in the other taxa led to unavoidable errors, well in excess
      of 20% in many. In 4 very weakly staining taxa, the mean fluorescence intensity
      in the heat-killed cells was higher than that of the living cells, which is
      inconsistent with the assumptions of the method. Applying the criteria of <=5%
      false negative plus <=5% false positive errors, and no significant loss of cells
      due to staining, FDA and FDA+CMFDA gave acceptably accurate results for only 8-10
      of 24 species (i.e., 33%-42%). CMFDA was the least effective stain and its
      addition to FDA did not improve the performance of FDA alone.

PMID- 27028463
TI  - Fall frequency and associated factors among men and women with or at risk for HIV
      infection.
AB  - OBJECTIVES: Falls and fall-related injuries are a major public health concern.
      HIV-infected adults have been shown to have a high incidence of falls.
      Identification of major risk factors for falls that are unique to HIV infection
      or similar to those in the general population will inform development of future
      interventions for fall prevention. METHODS: HIV-infected and uninfected men and
      women participating in the Hearing and Balance Substudy of the Multicenter AIDS
      Cohort Study and Women's Interagency HIV Study were asked about balance symptoms
      and falls during the prior 12 months. Falls were categorized as 0, 1, or >= 2;
      proportional odds logistic regression models were used to investigate
      relationships between falls and demographic and clinical variables and
      multivariable models were created. RESULTS: Twenty-four per cent of 303 HIV
      infected participants reported at least one fall compared with 18% of 233 HIV
      uninfected participants (P = 0.27). HIV-infected participants were
      demographically different from HIV-uninfected participants, and were more likely
      to report clinical imbalance symptoms (P <= 0.035). In univariate analyses, more
      falls were associated with hepatitis C, female sex, obesity, smoking, and
      clinical imbalance symptoms, but not age, HIV serostatus or other comorbidities.
      In multivariable analyses, female sex and imbalance symptoms were independently
      associated with more falls. Among HIV-infected participants, smoking, a higher
      number of medications, and imbalance symptoms remained independent fall
      predictors, while current protease inhibitor use was protective. CONCLUSIONS:
      Similar rates of falls among HIV-infected and uninfected participants were
      largely explained by a high prevalence of imbalance symptoms. Routine assessment
      of falls and dizziness/imbalance symptoms should be considered, with
      interventions targeted at reducing symptomatology.

PMID- 27028466
TI  - Therapeutic Whole-body Hypothermia Protects Remote Lung, Liver, and Kidney
      Injuries after Blast Limb Trauma in Rats.
AB  - BACKGROUND: Severe blast limb trauma (BLT) induces distant multiple-organ
      injuries. In the current study, the authors determined whether whole-body
      hypothermia (WH) and its optimal duration (if any) afford protection to the local
      limb damage and distant lung, liver, and kidney injuries after BLT in rats.
      METHODS: Rats with BLT, created by using chartaceous electricity detonators, were
      randomly treated with WH for 30 min, 60 min, 3 h, and 6 h (n = 12/group). Rectal
      temperature and arterial blood pressure were monitored throughout. Blood and
      lung, liver, and kidney tissue samples were harvested for measuring tumor
      necrosis factor-alpha, interleukin-6 and interleukin-10, myeloperoxidase
      activity, hydrogen sulfide, and biomarkers of oxidative stress at 6 h after BLT.
      The pathologic lung injury and the water content of the lungs, liver, and kidneys
      and blast limb tissue were assessed. RESULTS: Unlike WH for 30 min, WH for 60 min
      reduced lung water content, lung myeloperoxidase activity, and kidney
      myeloperoxidase activity by 10, 39, and 28% (all P < 0.05), respectively. WH for
      3 h attenuated distant vital organs and local traumatic limb damage and reduced
      myeloperoxidase activity, hydrogen peroxide and malondialdehyde concentration,
      and tumor necrosis factor-alpha and interleukin-6 levels by up to 49% (all P <
      0.01). Likewise, WH for 6 h also provided protection to such injured organs but
      increased blood loss from traumatic limb. CONCLUSIONS: Results of this study
      indicated that WH may provide protection for distant organs and local traumatic
      limb after blast trauma, which warrants further study.

PMID- 27028464
TI  - General Anesthesia Causes Epigenetic Histone Modulation of c-Fos and Brain
      derived Neurotrophic Factor, Target Genes Important for Neuronal Development in
      the Immature Rat Hippocampus.
AB  - BACKGROUND: Early postnatal exposure to general anesthesia (GA) may be
      detrimental to brain development, resulting in long-term cognitive impairments.
      Older literature suggests that in utero exposure of rodents to GA causes
      cognitive impairments in the first-generation as well as in the second-generation
      offspring never exposed to GA. Thus, the authors hypothesize that transient
      exposure to GA during critical stages of synaptogenesis causes epigenetic changes
      in chromatin with deleterious effects on transcription of target genes crucial
      for proper synapse formation and cognitive development. They focus on the effects
      of GA on histone acetyltransferase activity of cAMP-responsive element-binding
      protein and the histone-3 acetylation status in the promoters of the target genes
      brain-derived neurotrophic factor and cellular Finkel-Biskis-Jinkins murine
      sarcoma virus osteosarcoma oncogene (c-Fos) known to regulate the development of
      neuronal morphology and function. METHODS: Seven-day-old rat pups were exposed to
      a sedative dose of midazolam followed by combined nitrous oxide and isoflurane
      anesthesia for 6 h. Hippocampal neurons and organotypic hippocampal slices were
      cultured in vitro and exposed to GA for 24 h. RESULTS: GA caused epigenetic
      modulations manifested as histone-3 hypoacetylation (decrease of 25 to 30%, n = 7
      to 9) and fragmentation of cAMP-responsive element-binding protein (two-fold
      increase, n = 6) with 25% decrease in its histone acetyltransferase activity,
      which resulted in down-regulated transcription of brain-derived neurotrophic
      factor (0.2- to 0.4-fold, n = 7 to 8) and cellular Finkel-Biskis-Jinkins murine
      sarcoma virus osteosarcoma oncogene (about 0.2-fold, n = 10 to 12). Reversal of
      histone hypoacetylation with sodium butyrate blocked GA-induced morphological and
      functional impairments of neuronal development and synaptic communication.
      CONCLUSION: Long-term impairments of neuronal development and synaptic
      communication could be caused by GA-induced epigenetic phenomena.

PMID- 27028468
TI  - Driving Performance of Residents after Six Consecutive Overnight Work Shifts.
AB  - BACKGROUND: Residency training requires work in clinical settings for extended
      periods of time, resulting in altered sleep patterns, sleep deprivation, and
      potentially deleterious effects on safe performance of daily activities,
      including driving a motor vehicle. METHODS: Twenty-nine anesthesiology resident
      physicians in postgraduate year 2 to 4 drove for 55 min in the Virginia Driving
      Safety Laboratory using the Driver Guidance System (MBFARR, LLC, USA). Two
      driving simulator sessions were conducted, one experimental session immediately
      after the final shift of six consecutive night shifts and one control session at
      the beginning of a normal day shift (not after call). Both sessions were
      conducted at 8:00 AM. Psychomotor vigilance task testing was employed to evaluate
      reaction time and lapses in attention. RESULTS: After six consecutive night
      shifts, residents experienced significantly impaired control of all the driving
      variables including speed, lane position, throttle, and steering. They were also
      more likely to be involved in collisions. After six consecutive night shifts,
      residents had a significant increase in reaction times (281.1 vs. 298.5 ms; P =
      0.001) and had a significant increase in the number of both minor (0.85 vs. 1.88;
      P = 0.01) and major lapses (0.00 vs. 0.31; P = 0.008) in attention. CONCLUSIONS:
      Resident physicians have greater difficulty controlling speed and driving
      performance in the driving simulator after six consecutive night shifts. Reaction
      times are also increased with emphasis on increases in minor and major lapses in
      attention after six consecutive night shifts.

PMID- 27028469
TI  - Convergent Validity of Three Methods for Measuring Postoperative Complications.
AB  - BACKGROUND: Anesthesiologists need tools to accurately track postoperative
      outcomes. The accuracy of patient report in identifying a wide variety of
      postoperative complications after diverse surgical procedures has not previously
      been investigated. METHODS: In this cohort study, 1,578 adult surgical patients
      completed a survey at least 30 days after their procedure asking if they had
      experienced any of 18 complications while in the hospital after surgery. Patient
      responses were compared to the results of an automated electronic chart review
      and (for a random subset of 750 patients) to a manual chart review. Results from
      automated chart review were also compared to those from manual chart review.
      Forty-two randomly selected patients were contacted by telephone to explore
      reasons for discrepancies between patient report and manual chart review.
      RESULTS: Comparisons between patient report, automated chart review, and manual
      chart review demonstrated poor-to-moderate positive agreement (range, 0 to 58%)
      and excellent negative agreement (range, 82 to 100%). Discordance between patient
      report and manual chart review was frequently explicable by patients reporting
      events that happened outside the time period of interest. CONCLUSIONS: Patient
      report can provide information about subjective experiences or events that happen
      after hospital discharge, but often yields different results from chart review
      for specific in-hospital complications. Effective in-hospital communication with
      patients and thoughtful survey design may increase the quality of patient
      reported complication data.

PMID- 27028470
TI  - A 1966 Anesthetic Administered by Robert D. Dripps, M.D., Demonstrated His
      Experimental Style of Clinical Care.
AB  - Robert D. Dripps, M.D. (1911 to 1973), helped found academic anesthesiology.
      Newly reviewed teaching slides from the University of Pennsylvania (Philadelphia,
      Pennsylvania) contain six anesthesia records from 1965 to 1967 that involved
      Dripps. They illustrate the clinical philosophy he taught-to consider
      administration of each anesthetic a research study. Intense public criticism in
      1967 for improper experimentation on patients during anesthesia changed his
      clinical and research philosophies and teaching. 

PMID- 27028471
TI  - Anesthetic Records: Lessons about Ethics and Education.

PMID- 27028472
TI  - Without Science There Is Little Art in Anesthesiology: 2015 Rovenstine Lecture.

PMID- 27028473
TI  - Blind Spot: Are We Neglecting House Staff Driving Safety in the Era of Duty Hour
      Regulations? Driving Performance of Residents after Six Consecutive Overnight
      Work Shifts.

PMID- 27028474
TI  - Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in
      collagen degradation, as a target for anticancer drugs.
AB  - The main group of enzymes responsible for the collagen and other protein
      degradation in extracellular matrix (ECM) are matrix metalloproteinases (MMPs).
      Collagen is the main structural component of connective tissue and its
      degradation is a very important process in the development, morphogenesis, tissue
      remodeling, and repair. Typical structure of MMPs consists of several distinct
      domains. MMP family can be divided into six groups: collagenases, gelatinases,
      stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs.
      MMPs and their inhibitors have multiple biological functions in all stages of
      cancer development: from initiation to outgrowth of clinically relevant
      metastases and likewise in apoptosis and angiogenesis. MMPs and their inhibitors
      are extensively examined as potential anticancer drugs. MMP inhibitors can be
      divided into two main groups: synthetic and natural inhibitors. Selected
      synthetic inhibitors are in clinical trials on humans, e.g. synthetic peptides,
      non-peptidic molecules, chemically modified tetracyclines, and bisphosphonates.
      Natural MMP inhibitors are mainly isoflavonoids and shark cartilage.

PMID- 27028475
TI  - Determining the Presence of Thin-Walled Regions at High-Pressure Areas in
      Unruptured Cerebral Aneurysms by Using Computational Fluid Dynamics.
AB  - BACKGROUND: Thin-walled regions (TWRs) of cerebral aneurysms are at high risk of
      rupture, and careful attention should be paid during surgical procedures. Despite
      this, an optimal imaging technique to estimate TWRs has not been established.
      Previously, pressure elevation at TWRs was reported with computational fluid
      dynamics (CFD) but not fully evaluated. OBJECTIVE: To investigate the possibility
      of predicting aneurysmal TWRs at high-pressure areas with CFD. METHODS: Fifty
      unruptured middle cerebral artery aneurysms were analyzed. Spatial and temporal
      maximum pressure (Pmax) areas were determined with a fluid-flow formula under
      pulsatile blood flow conditions. Intraoperatively, TWRs of aneurysm domes were
      identified as reddish areas relative to the healthy normal middle cerebral
      arteries; 5 neurosurgeons evaluated and divided these regions according to Pmax
      area and TWR correspondence. Pressure difference (PD) was defined as the degree
      of pressure elevation on the aneurysmal wall at Pmax and was calculated by
      subtracting the average pressure from the Pmax and dividing by the dynamic
      pressure at the aneurysm inlet side for normalization. RESULTS: In 41 of the 50
      cases (82.0%), the Pmax areas and TWRs corresponded. PD values were significantly
      higher in the correspondence group than in the noncorrespondence group (P =
      .008). A receiver-operating characteristic curve demonstrated that PD accurately
      predicted TWRs at Pmax areas (area under the curve, 0.764; 95% confidence
      interval, 0.574-0.955; cutoff value, 0.607; sensitivity, 66.7%; specificity,
      82.9%). CONCLUSION: A high PD may be a key parameter for predicting TWRs in
      unruptured cerebral aneurysms. ABBREVIATIONS: CFD, computational fluid
      dynamicsMCA, middle cerebral arteryPave, average pressurePD, pressure
      differencePmax, maximum pressureTWR, thin-walled regionWSS, wall shear stress.

PMID- 27028476
TI  - In Reply: Safety and Efficacy Issues of Tirofiban Use in Endovascular Procedures:
      What Are the Actual Indications?

PMID- 27028477
TI  - Letter: How Long Should We Wait for Delivery Treatment After Surgery? An Enigma
      Yet to Be Solved.

PMID- 27028478
TI  - In Reply: How Long Should We Wait for Delivery Treatment After Surgery? An Enigma
      Yet to Be Solved.

PMID- 27028479
TI  - Couples Exploring Nonmonogamy: Guidelines for Therapists.
AB  - A population that is potentially challenging for couple and family therapists to
      work with is that of couples who want to explore nonmonogamy. For many
      therapists, nonmonogamy challenges personal values and beliefs, and there is
      little in the literature to support therapists in achieving cultural competency
      in this area. Based on a review of Western clinical literature over the past 20
      years and on the author's clinical experience, the author provides therapists
      with guidelines to use with couples who want to explore the possibility of
      becoming nonmonogamous. The guidelines include (a) educating oneself about
      nonmonogamy; (b) identifying one's own values and beliefs related to nonmonogamy;

PMID- 27028480
TI  - Screening for SLC7A14 gene mutations in patients with autosomal recessive or
      sporadic retinitis pigmentosa.
AB  - PURPOSE: In this study, we aimed to detect mutations in the SLC7A14 cationic
      transporter gene, which has recently been reported as a causative gene for
      retinitis pigmentosa (RP), in Japanese patients with autosomal recessive (AR) or
      sporadic RP. MATERIALS AND METHODS: We included 146 unrelated Japanese patients
      with AR or sporadic RP who lacked mutations in genes known to be associated with
      RP despite next-generation sequencing-based screening. We sequenced the seven
      SLC7A14 coding exons along with their flanking intronic DNA using the Sanger
      method. The detected polymorphisms were assessed for their pathogenicity with in
      silico prediction tools. For those who had heterozygous, nonsynonymous variants,
      we performed multiplex ligation-dependent probe amplification (MLPA) to search
      for additional deletion/duplication. RESULTS: We detected four distinct SLC7A14
      polymorphisms excluding synonymous polymorphisms. Two of these polymorphisms were
      assessed as detrimental by in silico prediction tools. However, all of the
      mutations were heterozygous. Neither homozygous polymorphisms nor compound
      heterozygous polymorphisms, which are considered detrimental variants, were
      detected. Neither deletion nor duplication was found with MLPA in patients with
      heterozygous variants. CONCLUSIONS: The four SLC7A14 mutations detected herein
      were unlikely to be pathogenic in this Japanese cohort. The frequency and
      pathogenicity of SLC7A14 mutations may vary depending on ethnicity, and these
      mutations may be rare in Japanese patients.

PMID- 27028481
TI  - Patients With Psoriasis and Personalized Trade-offs in Treatment Decisions
      Lessons Learned From Focus Groups.

PMID- 27028482
TI  - Cytologic subclassification of atypia of undetermined significance may predict
      thyroid nodules more likely to be malignant at surgery.
AB  - BACKGROUND: The atypia of undetermined significance or follicular lesion of
      undetermined significance (AUS/FLUS) category in the Bethesda System of reporting
      thyroid fine-needle aspiration (FNA) includes various cytological findings
      considered to have a low risk of malignancy. It is still unclear if any
      particular subset of the cytological findings within this category carries a
      higher risk for malignancy requiring a more aggressive treatment plan. METHODS:
      We reviewed 221 AUS/FLUS FNAs performed between January of 2006 and May of 2012.
      Histopathological data from surgery was available in 101 nodules and
      characteristics of these nodules were analyzed. We reviewed the initial cytology
      report and subclassified the nodules into one of four groups: architectural
      atypia (AA, includes abnormal follicular arrangement but no cellular
      abnormalities), cellular atypia (CA, atypical cellular findings) with or without
      AA, Hurthle cells Predominant and Others that included otherwise unspecified AUS
      categories. The surgical pathology confirmed malignancy rate for each group was
      calculated. RESULT: Papillary thyroid carcinoma was the most common malignancy
      identified (26 of 29 or 90%). We found that in the AA only category, 2/21 (10%)
      nodules were malignant, whereas when CA with or without AA was present, 23/66
      (35%) were malignant, significantly higher than the former group (P values of
      0.025). CONCLUSION: CA seen on initial AUS/FLUS had a higher malignancy rate
      compared to AA group. Further research is required to consider subclassification
      of this category to assign appropriate risk of malignancy for AUS nodules. Diagn.
      Cytopathol. 2016;44:492-498. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028483
TI  - PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or
      intrauterine growth restriction.
AB  - Placental growth factor (PlGF) is an angiogenic molecule produced by the placenta
      and implicated in the pathogenesis of preeclampsia (PE) and intrauterine growth
      restriction (IUGR). We have evaluated utility and applicability of the PlGF test
      in a clinical setting of pregnancies at risk of PE or complicated by IUGR in
      order to assess its relationship with pregnancy outcomes. Seventy-three
      pregnancies were enrolled between 19 and 35 weeks: 57 pregnancies at risk of PE
      and 16 at diagnosis of IUGR. Maternal circulating PlGF levels were measured by
      the Triage PlGF test (Alere, San Diego, CA). Pregnancy outcomes were evaluated in
      relation to three categories of plasma PlGF levels: very low (<12 pg/ml), low (12
      100 pg/ml) and normal (>=100 pg/ml). Uterine artery Doppler velocimetry (UADV)
      pulsatility index (PI) was measured in the same patients on the day of maternal
      sampling. Pregnancies at risk with very low plasma PlGF levels had significantly
      lower gestational age at delivery than patients with low or normal PlGF. The rate
      of emergency C-section was significantly higher in the group with PlGF <12 pg/ml.
      IUGR pregnancies with very low and low PlGF delivered earlier than patients with
      normal PlGF. All IUGR with very low and low PlGF had UADV PI > 95th percentile.
      Our data indicate that PlGF may provide useful information to identify fetuses
      requiring increased surveillance and possibly urgent delivery in pregnancies at
      risk of adverse outcomes. Furthermore, in IUGR, PlGF can predict adverse
      pregnancy outcomes that may be secondary to placental insufficiency.

PMID- 27028484
TI  - Characterizing the subjective experience of episodic past, future, and
      counterfactual thinking in healthy younger and older adults.
AB  - Recent evidence demonstrates remarkable overlap in the neural and cognitive
      mechanisms underlying episodic memory, episodic future thinking, and episodic
      counterfactual thinking. However, the extent to which the phenomenological
      characteristics associated with these mental simulations change as a result of
      ageing remains largely unexplored. The current study employs adapted versions of
      the Memory Characteristics Questionnaire and the Autobiographical Interview to
      compare the phenomenological characteristics associated with both positive and
      negative episodic past, future, and counterfactual simulations in younger and
      older adults. Additionally, it explores the influence of perceived likelihood in
      the experience of such simulations. The results indicate that, across all
      simulations, older adults generate more external details and report higher
      ratings of vividness, composition, and intensity than young adults. Conversely,
      younger adults generate more internal details across all conditions and rated
      positive and negative likely future events as more likely than did older adults.
      Additionally, both younger and older adults reported higher ratings for sensory,
      composition, and intensity factors during episodic memories relative to future
      and counterfactual thoughts. Finally, for both groups, ratings of spatial
      coherence and composition were higher for likely counterfactuals than for both
      unlikely counterfactuals and future simulations. Implications for the psychology
      of mental simulation and ageing are discussed.

PMID- 27028485
TI  - Core food intakes of Australian children aged 9-10 years: nutrients, daily
      servings and diet quality in a community cross-sectional sample.
AB  - BACKGROUND: The present study aimed to evaluate core food intakes in 9-10-year
      old Australian children by considering adequacy of nutrient intakes, comparing
      servings of core food groups with Australian recommendations and scoring overall
      diet quality. METHODS: Children from an established community-based cohort study
      completed a semi-quantitative food frequency questionnaire. Daily intakes of
      energy, macronutrients, micronutrients, servings of core (i.e. nutrient-rich)
      foods and a diet quality index were calculated and compared with appropriate
      standards. Sex and socio-economic differences were examined. RESULTS: The 436
      children participating were from low to high socio-economic status families. As a
      group, over half of the children met estimated average requirements for key macro
      and micronutrients, with the exception of fibre (inadequate in 41% of boys and
      24% of girls). Children obtained 55% of their daily energy from core foods. Most
      children had fewer than the recommended servings of vegetables (91%) and
      meat/alternatives (99.8%), whereas boys generally ate fewer servings of grains
      and cereals than recommended (87%), and girls ate fewer servings of dairy (83%).
      Diet quality scores indicated room for improvement (median score of 26 for boys
      and 25 for girls, out of a maximum of 73 points). CONCLUSIONS: As a group, a
      large proportion of children were able to meet their daily nutrient requirements.
      However, achieving this through noncore foods meant that diets were high in salt,
      saturated fat and sugar; more servings of core foods and greater dietary
      diversity would be preferable. These results suggest that families need more
      support to optimise dietary patterns of children in this age group.

PMID- 27028486
TI  - Using Raw VAR Regression Coefficients to Build Networks can be Misleading.
AB  - Many questions in the behavioral sciences focus on the causal interplay of a
      number of variables across time. To reveal the dynamic relations between the
      variables, their (auto- or cross-) regressive effects across time may be
      inspected by fitting a lag-one vector autoregressive, or VAR(1), model and
      visualizing the resulting regression coefficients as the edges of a weighted
      directed network. Usually, the raw VAR(1) regression coefficients are drawn, but
      we argue that this may yield misleading network figures and characteristics
      because of two problems. First, the raw regression coefficients are sensitive to
      scale and variance differences among the variables and therefore may lack
      comparability, which is needed if one wants to calculate, for example, centrality
      measures. Second, they only represent the unique direct effects of the variables,
      which may give a distorted picture when variables correlate strongly. To deal
      with these problems, we propose to use other VAR(1)-based measures as edges.
      Specifically, to solve the comparability issue, the standardized VAR(1)
      regression coefficients can be displayed. Furthermore, relative importance
      metrics can be computed to include direct as well as shared and indirect effects
      into the network. 

PMID- 27028487
TI  - Correction: Meta-Research: Broadening the Scope of PLOS Biology.

PMID- 27028488
TI  - Tenogenesis of bone marrow-, adipose-, and tendon-derived stem cells in a dynamic
      bioreactor.
AB  - Tendons are frequently damaged and fail to regenerate, leading to pain, loss of
      function, and reduced quality of life. Mesenchymal stem cells (MSCs) possess
      clinically useful tissue-regenerative properties and have been exploited for use
      in tendon tissue engineering and cell therapy. However, MSCs exhibit phenotypic
      heterogeneity based on the donor tissue used, and the efficacy of cell-based
      treatment modalities may be improved by optimizing cell source based on relative
      differentiation capacity. Equine MSCs were isolated from bone marrow (BM),
      adipose (AD), and tendon (TN), expanded in monolayer prior to seeding on
      decellularized tendon scaffolds (DTS), and cell-laden constructs were placed in a
      bioreactor designed to mimic the biophysical environment of the tendon. It was
      hypothesized that TN MSCs would differentiate toward a tendon cell phenotype
      better than BM and AD MSCs in response to a conditioning period involving cyclic
      mechanical stimulation for 1 hour per day at 3% strain and 0.33 Hz. All cell
      types integrated into DTS adopted an elongated morphology similar to tenocytes,
      expressed tendon marker genes, and improved tissue mechanical properties after 11
      days. TN MSCs expressed the greatest levels of scleraxis, collagen type-I, and
      cartilage oligomeric matrix protein. Major histocompatibility class-II protein
      mRNA expression was not detected in any of the MSC types, suggesting low
      immunogenicity for allogeneic transplantation. The results suggest that TN MSCs
      are the ideal cell type for regenerative medicine therapies for tendinopathies,
      exhibiting the most mature tendon-like phenotype in vitro. When TN MSCs are
      unavailable, BM or AD MSCs may serve as robust alternatives.

PMID- 27028489
TI  - Numerical study of incommensurate and decoupled phases of spin-1/2 chains with
      isotropic exchange J1, J2 between first and second neighbors.
AB  - The spin-1/2 chain with isotropic exchange J1, J2 > 0 between first and second
      neighbors is frustrated for either sign of J1 and has a singlet ground state (GS)
      for J1/J2 ? -4. Its rich quantum phase diagram supports gapless, gapped,
      commensurate (C), incommensurate (IC) and other phases. Critical points J1/J2 are
      evaluated using exact diagonalization and density matrix renormalization group
      calculations. The wave vector qG of spin correlations is related to GS degeneracy
      and obtained as the peak of the spin structure factor S(q). Variable qG indicates
      IC phases in two J1/J2 intervals, [-4, - 1.24] and [0.44, 2], and a C-IC point at
      J1/J2 = 2. The decoupled C phase in [-1.24, 0.44] has constant qG = pi/2,
      nondegenerate GS, and a lowest triplet state with broken spin density on
      sublattices of odd and even numbered sites. The lowest triplet and singlet
      excitations, E m and Esigma, are degenerate in finite systems at specific
      frustration J1/J2. Level crossing extrapolates in the thermodynamic limit to the
      same critical points as qG. The S(q) peak diverges at qG = pi in the gapless
      phase with J1/J2 > 4.148 and quasi-long-range order (QLRO(pi)). S(q) diverges at
      +/-pi/2 in the decoupled phase with QLRO(pi/2), but is finite in gapped phases
      with finite-range correlations. Numerical results and field theory agree at small
      J2/J1 but disagree for the decoupled phase with weak exchange J1 between
      sublattices. Two related models are summarized: one has an exact gapless
      decoupled phase with QLRO(pi/2) and no IC phases; the other has a single IC phase
      without a decoupled phase in between.

PMID- 27028490
TI  - Can Community and School-Based Supports Improve the Achievement of First
      Generation Immigrant Children Attending High-Poverty Schools?
AB  - Using a quasi-experimental design, the effects of a student support intervention
      were estimated for the math and reading achievement of first-generation immigrant
      children (n = 667, M = 11.05 years of age) attending high-poverty, urban
      elementary schools. The intervention was designed to help schools identify
      developmental strengths and barriers to learning and, in turn, connect children
      to community and school supports aligned with their strengths and needs. By
      exploiting within-school changes in the implementation of the intervention, the
      present study revealed statistically and practically significant treatment
      effects indicating improvements in math and reading achievement at the end of
      elementary school. In addition, the intervention appears to considerably narrow
      achievement gaps between English language learners and immigrant children
      proficient in English.

PMID- 27028491
TI  - Impact of Nanosize on Supercapacitance: Study of 1D Nanorods and 2D Thin-Films of
      Nickel Oxide.
AB  - We synthesized unique one-dimensional (1D) nanorods and two-dimensional (2D) thin
      films of NiO on indium-tin-oxide thin-films using a hot-filament metal-oxide
      vapor deposition technique. The 1D nanorods have an average width and length of
      ~100 and ~500 nm, respectively, and the densely packed 2D thin-films have an
      average thickness of ~500 nm. The 1D nanorods perform as parallel units for
      charge storing. However, the 2D thin-films act as one single unit for charge
      storing. The 2D thin-films possess a high specific capacitance of ~746 F/g
      compared to 1D nanorods (~230 F/g) using galvanostatic charge-discharge
      measurements at a current density of 3 A/g. Because the 1D NiO nanorods provide
      more plentiful surface areas than those of the 2D thin-films, they are fully
      active at the first few cycles. However, the capacitance retention of the 1D
      nanorods decays faster than that of the 2D thin-films. Also, the 1D NiO nanorods
      suffer from instability due to the fast electrochemical dissolution and high
      nanocontact resistance. Electrochemical impedance spectroscopy verifies that the
      low dimensionality of the 1D NiO nanorods induces the unavoidable effects that
      lead them to have poor supercapacitive performances. On the other hand, the slow
      electrochemical dissolution and small contact resistance in the 2D NiO thin-films
      favor to achieve high specific capacitance and great stability. 

PMID- 27028492
TI  - TP63 mutation in a patient with acro-dermo-ungual-lacrimal-tooth syndrome:
      Additional evidence of molecular overlap of the ADULT and EEC syndromes.

PMID- 27028494
TI  - Are Private Interests Clouding the Peer-Review Process of the WHO Bulletin? A
      Case Study.
AB  - Readers' trust on the medical literature has been eroded, and journal editors and
      some editorial boards are taking measures to ensure that authors fully and
      accurately report research findings and disclose conflicts of interest. This
      article describes a case study in which the papers editor of the World Health
      Organization (WHO) Bulletin influenced the content of an article that had been
      approved by the external reviewers. The editor objected to the publication of the
      large price differentials of the new molecular entities (NMEs) across the Latin
      American countries where they had been tested and the limited added therapeutic
      value of the NMEs that had been assessed by independent drug bulletins. This
      article summarizes the exchanges with WHO staff and posits the hypothesis that
      the WHO Bulletin might be affected by the shifts in WHO financing. Several
      authors have raised concern about the impact of financial conflicts of interest
      in WHO activities in the field of nutrition, intellectual property, and in the
      emergency response to the flu pandemic. Moreover, it has been reported that
      powerful WHO contributors pressured WHO into revising its publication policy.
      This is the first time that authors question if these conflicts of interest are
      also affecting the editorial independence of the WHO Bulletin.

PMID- 27028493
TI  - Measurement of arteriolar blood volume in brain tumors using MRI without
      exogenous contrast agent administration at 7T.
AB  - PURPOSE: Arteriolar cerebral-blood-volume (CBVa) is an important perfusion
      parameter that can be measured using inflow-based vascular-space-occupancy
      (iVASO) MRI without exogenous contrast agent administration. The purpose of this
      study is to assess the potential diagnostic value of CBVa in brain tumor patients
      by comparing it with total-CBV (including arterial, capillary and venous vessels)
      measured by dynamic-susceptibility-contrast (DSC) MRI. MATERIALS AND METHODS:
      Twelve brain tumor patients were scanned using iVASO (on 7T as part of a research
      project) and DSC (on 3T as part of routine clinical protocols) MRI. Region-of
      interest analysis was performed to compare the resulting perfusion measures
      between tumoral and contralateral regions, and to evaluate their associations
      with tumor grades. RESULTS: CBVa measured by iVASO MRI significantly correlated
      with WHO grade (rho = 0.37, P = 0.04). Total-CBV measured by DSC MRI showed a
      trend of correlation with WHO grade (rho = 0.28, P = 0.5). The signal-to-noise
      ratio was comparable (P > 0.1) between the two methods, while the contrast-to
      noise ratio between tumoral and contralateral regions was higher in iVASO-CBVa
      than DSC-CBV in WHO II/III patients (P < 0.05) but comparable in WHO IV patients
      (P > 0.1). A trend of positive correlation between DSC-CBV and iVASO-CBVa was
      observed (R2 = 0.28, P = 0.07). CONCLUSION: In this initial patient study, CBVa
      demonstrated a stronger correlation with WHO grade than total-CBV. Further
      investigation with a larger cohort is warranted to validate whether CBVa can be a
      better classifier than total-CBV for the stratification of brain tumors, and
      whether iVASO MRI can be a useful alternative method for the assessment of tumor
      perfusion, especially when exogenous contrast agent administration is difficult
      in certain patient populations. J. Magn. Reson. Imaging 2016;44:1244-1255.

PMID- 27028495
TI  - Are the bipolar disorders best modelled categorically or dimensionally?
AB  - OBJECTIVE: Considerable debate exists as to whether the bipolar disorders are
      best classified according to a categorical or dimensional model. This study
      explored whether there is evidence for a single or multiple subpopulations and
      the degree to which differing diagnostic criteria correspond to bipolar
      subpopulations. METHOD: A mixture analysis was performed on 1081 clinically
      diagnosed (and a reduced sample of 497 DSM-IV diagnosed) bipolar I and II
      disorder patients, using scores on hypomanic severity (as measured by the Mood
      Swings Questionnaire). Mixture analyses were conducted using two differing
      diagnostic criteria and two DSM markers to ascertain the most differentiating and
      their associated clinical features. RESULTS: The two subpopulation solution was
      most supported although the entropy statistic indicated limited separation and
      there was no distinctive point of rarity. Quantification by the odds ratio
      statistic indicated that the clinical diagnosis (respecting DSM-IV criteria, but
      ignoring 'high' duration) was somewhat superior to DSM-IV diagnosis in allocating
      patients to the putative mixture analysis groups. The most differentiating
      correlate was the presence or absence of psychotic features. CONCLUSION: Findings
      favour the categorical distinction of bipolar I and II disorders and argue for
      the centrality of the presence or absence of psychotic features to subgroup
      differentiation.

PMID- 27028496
TI  - A virtual sizing tool for mitral valve annuloplasty.
AB  - Functional mitral regurgitation, a backward leakage of the mitral valve, is a
      result of left ventricular growth and mitral annular dilatation. Its gold
      standard treatment is mitral annuloplasty, the surgical reduction in mitral
      annular area through the implantation of annuloplasty rings. Recurrent
      regurgitation rates may, however, be as high as 30% and more. While the degree of
      annular downsizing has been linked to improved long-term outcomes, too aggressive
      downsizing increases the risk of ring dehiscences and significantly impairs
      repair durability. Here, we prototype a virtual sizing tool to quantify changes
      in annular dimensions, surgically induced tissue strains, mitral annular
      stretches, and suture forces in response to mitral annuloplasty. We create a
      computational model of dilated cardiomyopathy onto which we virtually implant
      annuloplasty rings of different sizes. Our simulations confirm the common
      intuition that smaller rings are more invasive to the surrounding tissue, induce
      higher strains, and require larger suture forces than larger rings: The total
      suture force was 2.2 N for a 24-mm ring, 1.9 N for a 28-mm ring, and 0.8 N for a
      32-mm ring. Our model predicts the highest risk of dehiscence in the septal and
      postero-lateral annulus where suture forces are maximal. These regions co
      localize with regional peaks in myocardial strain and annular stretch. Our study
      illustrates the potential of realistic predictive simulations in cardiac surgery
      to identify areas at risk for dehiscence, guide the selection of ring size and
      shape, rationalize the design of smart annuloplasty rings and, ultimately,
      improve long-term outcomes after surgical mitral annuloplasty. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27028497
TI  - Geriatric Assessments and Association With VACS Index Among HIV-Infected Older
      Adults in San Francisco.
AB  - OBJECTIVES: To perform geriatric assessments in older HIV-infected adults in San
      Francisco and examine the association with age and the Veterans Aging Cohort
      Study (VACS) index scores. METHODS: A cross-sectional study was conducted from
      2012 to 2014 among HIV-infected patients >=50 years at 2 San Francisco-based HIV
      clinics. We evaluated 4 health domains: (1) physical health and function
      (activities of daily living), instrumental activities of daily living (IADL),
      falls, gait speed, (2) social support (physical and perceived support,
      loneliness), (3) mental health (depression, anxiety, posttraumatic stress
      disorder) and cognition, and (4) behavioral and general health (antiretroviral
      adherence and quality of life). Contingency table and rank-sum analyses examined
      associations between these domains with age and VACS index scores. RESULTS: Three
      hundred fifty-nine patients completed assessments (median age 57; 85% male; 57%
      white; 72% >high school education). On functional assessment, 39% reported
      dependence with >=1 IADL, and 40% reported falls in the previous year. Fifty
      eight percent experienced loneliness, 60% the lowest levels of perceived social
      support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had
      possible mild cognitive impairment. Thirty percent reported poor or fair quality
      of life. Older age was associated with lower CD4 counts, balance problems, slower
      gait, lower anxiety, poorer general health, and higher antiretroviral adherence.
      VACS Index score was associated with dependence in >=1 IADL and antiretroviral
      adherence. CONCLUSION: In a large sample of older HIV-infected adults, multiple
      significant aging-related conditions were identified. Integrating geriatric
      assessment tools into HIV/AIDS clinical care may help target interventions to
      optimize clinical care and quality of life for older HIV-infected individuals.

PMID- 27028498
TI  - High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV
      in an Emergency Department.
AB  - Earlier intervention in acute HIV infection limits HIV reservoirs and may
      decrease HIV transmission. We developed criteria for empiric antiretroviral
      therapy (ART) in an emergency department (ED) routine HIV screening program. We
      assessed the feasibility and willingness of patients with suspected acute HIV
      infection in the ED to begin ART. A suspected acute HIV infection was defined as
      a positive HIV antigen antibody combination immunoassay with pending HIV-antibody
      differentiation test results and HIV RNA viral load. During the study period,
      there were 16 confirmed cases of acute HIV infection: 11 met our criteria for
      empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED
      against medical advice without a prescription for ART. Eight patients completed
      at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well
      received by patients, and offers a unique entry point into the HIV care
      continuum.

PMID- 27028499
TI  - Diagnosis and Disclosure of HIV Status: Implications for Women's Risk of Physical
      Partner Violence in the Postpartum Period.
AB  - INTRODUCTION: This study prospectively examined whether HIV leads to elevated
      risk for intimate partner violence (IPV) for women and how this risk varies
      depending on HIV status disclosure to a partner. METHODS: We ran a series of
      logistic regression models using data from 1092 pregnant and postpartum women
      enrolled in an RCT in Durban, South Africa. Model 1 assessed whether baseline HIV
      status predicted 14-week postpartum physical IPV, controlling for baseline
      physical IPV, disclosure to partner, and demographic and study covariates. Model
      2 added the interaction between HIV status and disclosure. RESULTS: HIV was not
      associated with 14-week physical IPV in the main effects model [adjusted odds
      ratio: 1.34, 95% confidence interval (CI): 0.88 to 2.05]. However, there was a
      statistically significant positive interaction between HIV and disclosure
      (adjusted odds ratio: 0.22, 95% CI: 0.05 to 0.96). Among women who disclosed
      their HIV status, HIV was not significantly associated with 14-week IPV (adjusted
      odds ratio: 1.12, 95% CI: 0.71 to 1.89). However, among women who had not
      disclosed, the odds of reporting IPV at 14 weeks was 5.15 times higher for HIV
      positive women as compared with HIV-negative women (95% CI: 1.25 to 21.00).
      DISCUSSION: Although we established that HIV does not increase incidence of IPV
      for all HIV-positive women, we found an elevated risk of IPV among the HIV
      positive women who chose not to disclose their status to their partner.
      Nondisclosure is likely a marker for other problematic aspects of the
      relationship, and counselors should either find alternative safe options for
      disclosure or support women's decisions not to disclose.

PMID- 27028500
TI  - Persons Living With HIV in the United States: Fewer Than We Thought.
AB  - OBJECTIVES: To estimate the number of persons living with HIV (PLWH) in the
      United States and to describe their care status. METHODS: Estimates of diagnosed
      PLWH in New York City and other 19 jurisdictions based on HIV case reporting were
      compared with those based on HIV laboratory reporting. A revised HIV care
      continuum was constructed based on previously published data. RESULTS: The
      estimate of PLWH based on HIV case reporting was 25.6% higher than that based on
      HIV laboratory reporting data in New York City. There were 819,200 PLWH in the
      United States at the end of 2011 (plausible range: 809,800-828,800), of whom 86%
      were diagnosed, 72% were retained in care (>=1 care visit in 2011), 68% were on
      antiretroviral therapy, and 55% were virally suppressed (<=200 copies/mL).
      CONCLUSIONS: The current method based on HIV case reporting may have
      overestimated PLWH in the United States. While we continue cleaning HIV case
      reporting data to improve its quality, we should take the opportunity to use
      comprehensive HIV laboratory reporting data to estimate PLWH at both the national
      and local levels.

PMID- 27028501
TI  - Narrowing the Gap in Life Expectancy Between HIV-Infected and HIV-Uninfected
      Individuals With Access to Care.
AB  - BACKGROUND: It is unknown if a survival gap remains between HIV-infected and HIV
      uninfected individuals with access to care. METHODS: We conducted a cohort study
      within Kaiser Permanente California during 1996-2011, using abridged life tables
      to estimate the expected years of life remaining ("life expectancy") at age 20.
      RESULTS: Among 24,768 HIV-infected and 257,600 HIV-uninfected individuals, there
      were 2229 and 4970 deaths, with mortality rates of 1827 and 326 per 100,000
      person-years, respectively. In 1996-1997, life expectancies at age 20 for HIV
      infected and HIV-uninfected individuals were 19.1 and 63.4 years, respectively,
      corresponding with a gap of 44.3 years (95% confidence interval: 38.4 to 50.2).
      Life expectancy at age 20 for HIV-infected individuals increased to 47.1 years in
      2008 and 53.1 years by 2011, narrowing the gap to 11.8 years (8.9-14.8 years) in
      2011. In 2008-2011, life expectancies at age 20 for HIV-infected individuals
      ranged from a low of 45.8 years for blacks and 46.0 years for those with a
      history of injection drug use to a high of 52.2 years for Hispanics. HIV-infected
      individuals who initiated antiretroviral therapy with CD4 >=500 cells per
      microliter had a life expectancy at age 20 of 54.5 years in 2008-2011, narrowing
      the gap relative to HIV-uninfected individuals to 7.9 years (5.1-10.6 years). For
      these HIV-infected individuals, the gap narrowed further in subgroups with no
      history of hepatitis B or C infection, smoking, drug/alcohol abuse, or any of
      these risk factors. CONCLUSIONS: Even with early treatment and access to care, an
      8-year gap in life expectancy remains for HIV-infected compared with HIV
      uninfected individuals.

PMID- 27028502
TI  - Behavioral Interventions for Tobacco Use in HIV-Infected Smokers: A Meta
      Analysis.
AB  - CONTEXT: Smoking is responsible for increased morbidity and mortality in HIV
      infected smokers. OBJECTIVE: To assess the efficacy of behavioral interventions
      for smoking cessation among HIV-infected smokers compared with the standard care.
      DATA SOURCES: PubMed, Cochrane, CINHAL, PsychINFO, and Google Scholar were
      searched for randomized controlled trials published in English. STUDY SELECTION:
      Eligibility criteria were randomized controlled trials with targeted behavioral
      interventions compared with standard of care (or enhanced standard of care) aimed
      at promoting abstinence in HIV-infected smokers. A total of 17,384 articles were
      found and 17,371 were excluded; 13 full text articles were obtained and reviewed,
      and 8 met the eligibility criteria (Kappa = 0.94). DATA EXTRACTION: The primary
      outcome was expired carbon monoxide-verified 7-day point prevalence abstinence
      rates. Adequate sequence generation and freedom from incomplete or selective
      outcome reporting was used to assess study quality. RESULTS: A total of 1822
      subjects from 8 studies yielded a statistically significant effect of behavioral
      interventions in increasing abstinence in HIV-infected smokers with a moderate
      effect size (relative risk: 1.51; 95% confidence interval: 1.17 to 1.95). Those
      studies with interventions of 8 sessions or more had a large effect size for
      abstinence (relative risk: 2.88; 95% confidence interval: 1.89 to 4.61). When
      stratified by the number of sessions, there was no heterogeneity. CONCLUSIONS:
      Targeted behavioral smoking cessation interventions are efficacious.
      Interventions consisting of 8 sessions or more had the greatest treatment
      efficacy.

PMID- 27028503
TI  - Medication Use by Race and Ethnicity in Women Transitioning Through the
      Menopause: A Study of Women's Health Across the Nation Drug Epidemiology Study.
AB  - BACKGROUND: Medication utilization and costs increased over the last decade, but
      the effects of race/ethnicity have never been well studied in longitudinal data.
      We analyzed reports of prescription medication use to (1) identify trajectories
      of use and (2) determine predictors associated with a large increase in use.
      Specifically, variations in medication use by race/ethnicity were examined.
      METHODS: We analyzed the Study of Women's Health Across the Nation cohort with a
      median of 14 years of follow-up. Group-based trajectory models helped distinguish
      women with a low use of medications versus those with heavy use. Logistic
      regression was used to estimate the odds ratio (OR) for each racial/ethnic group
      associated with heavy use, controlling for potential baseline confounders.
      RESULTS: The 2,798 women sampled had a mean age of 46 years at baseline and the
      median number of medications at baseline was 2, increasing to 4 over the follow
      up period. Trajectory models identified that 16% of participants demonstrated
      heavy use of medications, from a median of 5 at baseline to 10 medications at
      final follow-up. Regression models controlling for age, obesity, number of
      comorbid conditions, and pain found that Hispanic (OR = 0.085, 95% confidence
      interval [CI]: 0.037-0.20), Chinese (OR = 0.32, 95% CI: 0.16-0.63), Japanese (OR
      = 0.33, 95% CI: 0.17-0.64), and Black (OR = 0.79, 95% CI: 0.57-1.11) women had
      lower odds for heavy use compared with White women. CONCLUSIONS: Longitudinal
      medication use among women in Study of Women's Health Across the Nation (SWAN)
      differed by race/ethnicity with non-White women having a lower odds of heavy use.

PMID- 27028504
TI  - Assessment of a program to encourage the multidisciplinary management of urinary
      disorders in multiple sclerosis.
AB  - AIMS: Urinary disorders (UD) secondary to multiple sclerosis (MS) are common and
      can be responsible for complications. Since 2004, we organized in our region
      their management through a neuro-urological activity and a care network that
      established and distributed an algorithm for screening and first line care. The
      objective was to assess the effects of this organization on the management of UD
      and its impact for patients. METHODS: Between January 2004 and December 2009, 328
      patients were seen in neuro-urological consultation. The data of a group of 168
      patients consulting during the deployment of our organization (before January
      2007: group 1) were compared to those of 160 patients taken when the organization
      was well established (from January 2007: group 2). In parallel, the modification
      of the prescription rate of the first-line examination patients was evaluated.
      RESULTS: The two groups were significantly different concerning age, duration of
      MS, EDSS score (Group 1 vs. Group 2 respectively 51.6 +/- 12.6 vs. 48 +/- 11.8
      years, P = 0.008; 19 +/- 9.7 vs. 13.8 +/- 10.5 years, P < 0.0001; 5.8 +/-2.0 vs.
      5.1 +/- 2.1, P = 0.008). The occurrence of urinary complications in group 1 was
      more frequent than in group 2 (66.3% vs. 40%, P < 0.0001). The rate of first-line
      examinations rose from 1/16 patient seen in January 2006 to 9/12 patients in
      January 2008. CONCLUSION: The multidisciplinary management of UD in MS led to
      patients being cared for sooner in the evolution of MS, with fewer complications
      and to an improvement in the rate of prescription of first-line examinations.
      Neurourol. Urodynam. 36:706-709, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028505
TI  - Efficacy and safety of ustekinumab in a group of 22 elderly patients with
      psoriasis over a 2-year period.

PMID- 27028507
TI  - Higher prevalence of dementia in patients with schizophrenia: A nationwide
      population-based study.
AB  - INTRODUCTION: This study investigates the prevalence of dementia in patients with
      and without schizophrenia, with a particular focus on age-specific and sex
      specific differences. METHODS: We conducted a population-based study using the
      National Health Insurance claims database from 2010 to 2013. Using a 10:1
      matching ratio, 248,919 patients without schizophrenia and 26,591 patients with
      schizophrenia were identified based on the ICD-10 code. Patients with dementia
      were extracted by diagnosis or use of anti-dementia drugs. Conditional logistic
      regression analyses were performed to evaluate the association between
      schizophrenia and dementia. RESULTS: The prevalence of dementia was significantly
      higher in schizophrenia patients compared with that in matched non-schizophrenia
      patients (9.9% versus 2.2%, P < 0.0001). After adjusting for Charlson comorbidity
      index and underlying comorbidities, conditional logistic regression showed that
      schizophrenia was associated with dementia (adjusted odds ratio [AOR], 4.7; 95%
      confidence interval [CI], 4.4-5.1). When stratified by sex, the AOR was 5.6 (95%
      CI, 5.0-6.2) among women and 4.0 (95% CI, 3.6-4.5) among men. Moreover, the
      association between dementia and schizophrenia was strong in elderly patients.
      The AOR of dementia prevalence was 6.6 (95% CI, 6.1-7.2) in patients aged >=65
      years and 3.4 (95% CI, 3.0-3.8) in patients aged <65 years. DISCUSSION:
      Schizophrenia patients were more likely to have dementia compared with non
      schizophrenia patients. This association seems greater in higher prevalence
      groups such as women and patients aged >=65 years. Further investigation on the
      mechanism is required.

PMID- 27028506
TI  - Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation
      of a Noncanonical Amino Acid.
AB  - Multiple-site-specific incorporation of a noncanonical amino acid into a
      recombinant protein would be a very useful technique to generate multiple
      chemical handles for bioconjugation and multivalent binding sites for the
      enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA
      synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon
      was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine
      (Phe) codons in a site-specific manner. However, due to the less selective codon
      recognition of the AAA anticodon, there was significant misincorporation of a
      noncanonical amino acid into unwanted UUC Phe codons. To enhance codon
      selectivity, we explored degenerate leucine (Leu) codons instead of Phe
      degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing
      the CAA anticodon and the yPheRS_naph variant allowed incorporation of a
      phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in
      response to multiple UUG Leu codons, but not to other Leu codon sites. Despite
      the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully
      demonstrated that the concept of forced ambiguity of the genetic code can be
      achieved for the Leu codons, available for multiple-site-specific incorporation. 

PMID- 27028508
TI  - Related factors of serum uric acid in patients with primary hypertension and
      hyperhomocysteinemia.
AB  - OBJECTIVE: To investigate the related factors of serum uric acid in patients with
      primary hypertension and hyperhomocysteinemia. METHODS: One hundred and ten
      patients with primary hypertension and hyperhomocysteinemia (homocysteine levels
      >10 MUmol/L) were enrolled into this study, ages from 18 years to 75 years. They
      were divided into the normal serum uric acid group which contained 74 cases
      patients (41 cases of male and 33 cases of female) and the hyperuricemia group
      which contained 36 cases patients (20 cases of male and 16 cases of female).
      Plasma concentrations of homocysteine, serum uric acid, serum folic acid, blood
      sugar, triglyceride, total cholesterol, serum low density lipoprotein
      cholesterol, serum high density lipoprotein cholesterol, blood urea nitrogen, and
      creatinine were detected in these patients, and the deference of them between the
      two groups was compared. And then the risk factors of serum uric acid with
      univariate analysis and multivariate analysis by logistic regression analysis
      were analyzed. RESULTS: The result of multivariate analysis showed that the
      incidence of serum uric acid in patients with primary hypertension and
      hyperhomocysteinemia had significant relationships with systolic blood pressure
      (OR [odds ratio]: 1.132, 95%CI [confidence interval]: 1.003~1.290, p = 0.043),
      diastolic blood pressure (OR: 1.353 95%CI: 1.023~1.789, p = 0.034, homocysteine
      (OR: 1.264, 95%CI: 1.016~1.573, p = 0.035), triglyceride (OR: 9.726, 95%CI:
      1.288~73.466, p = 0.027), and creatinine (OR: 1.031, 95%CI: 1.005~1.508, p =
      0.018). CONCLUSION: The indices of systolic blood pressure, diastolic blood
      pressure, homocysteine, triglyceride, and creatinine were important risk factors
      of serum uric acid in patients with primary hypertension and
      hyperhomocysteinemia. It is of great significance to measure multiple risk
      factors in patients with primary hypertension and hyperhomocysteinemia.

PMID- 27028509
TI  - Triplet-Polaron-Interaction-Induced Upconversion from Triplet to Singlet: a
      Possible Way to Obtain Highly Efficient OLEDs.
AB  - Two D-A-type molecules, 4-N-[4-(9-phenylcarbazole)]-3,5-bis(4
      diphenylamine)phenyl-4H-1,2,4-triazole and 4,4'-(9-(4-(1-phenyl-1H
      phenanthro[9,10-d]imidazol-2-yl)phenyl)-9H-carbazole-3,6-diyl) bis-(N,N
      diphenylaniline), are designed and synthesized. Organic lightemitting diodes
      based on them exhibit deep-blue emission and the singlet formation ratios are
      higher than the simple spin-statistics of 25%. A triplet-polaroninteraction
      induced upconversion from triplet to singlet through a one-electron transfer
      mechanism is proposed, and is proven by magnetocurrent measurement and quantum
      chemistry computation. 

PMID- 27028510
TI  - International comparison of liver transplant programmes: differences in
      indications, donor and recipient selection and outcome between Italy and UK.
AB  - BACKGROUND & AIMS: Comparing liver transplant (LT) programmes internationally can
      improve outcomes by stimulating cross-national learning. Yet, comparison of crude
      outcomes, by using registry data, is limited by missing data, not allowing proper
      risk-adjustment for donor- and recipient-related factors. The objective of this
      study was to compare two European LT programmes based on high-quality national
      longitudinal databases prospectively collected in Italy and UK respectively.
      METHODS: We undertook a multicentre, international cohort study including all
      adults who underwent a first single organ LT in Italy (N = 1480) and the UK (N =
      1003) between June 2007 and May 2009. RESULTS: Italian donors were much older
      compared to the UK ones. Hepatitis C virus infection and hepatocellular carcinoma
      had higher prevalence in the Italian cohort compared to the UK one (47.5% vs.
      23.1%, and 47.2% vs. 17.1% respectively). Centres' volume differed significantly,
      with five centres out of seven in UK vs. only two out of 20 in Italy performing
      >60 transplants per year. No national strategies to drive the donor-recipient
      matching were identified in both countries. After appropriate adjustment, a
      higher risk of early transplant loss was identified in the Italian cohort,
      whereas no differences were found in the 3-year survival rates. CONCLUSIONS:
      International comparison of LT programmes provides the opportunity for
      benchmarking between heterogeneous healthcare systems and should ideally become a
      vital part of national quality assurance programmes. This requires the
      implementation of a standardized methodology for data collection to appropriately
      weigh each country's patient case-mix and donor and recipients risk factors.

PMID- 27028511
TI  - A new cryptic cationic antimicrobial peptide from human apolipoprotein E with
      antibacterial activity and immunomodulatory effects on human cells.
AB  - Cationic antimicrobial peptides (AMPs) possess fast and broad-spectrum activity
      against both Gram-negative and Gram-positive bacteria, as well as fungi. It has
      become increasingly evident that many AMPs, including those that derive from
      fragments of host proteins, are multifunctional and able to mediate various
      immunomodulatory functions and angiogenesis. Among these, synthetic
      apolipoprotein-derived peptides are safe and well tolerated in humans and have
      emerged as promising candidates in the treatment of various inflammatory
      conditions. Here, we report the characterization of a new AMP corresponding to
      residues 133-150 of human apolipoprotein E. Our results show that this peptide,
      produced either by chemical synthesis or by recombinant techniques in Escherichia
      coli, possesses a broad-spectrum antibacterial activity. As shown for several
      other AMPs, ApoE (133-150) is structured in the presence of TFE and of membrane
      mimicking agents, like SDS, or bacterial surface lipopolysaccharide (LPS), and an
      anionic polysaccharide, alginate, which mimics anionic capsular exo
      polysaccharides of several pathogenic microorganisms. Noteworthy, ApoE (133-150)
      is not toxic toward several human cell lines and triggers a significant innate
      immune response, assessed either as decreased expression levels of
      proinflammatory cytokines in differentiated THP-1 monocytic cells or by the
      induction of chemokines released from PBMCs. This novel bioactive AMP also showed
      a significant anti-inflammatory effect on human keratinocytes, suggesting its
      potential use as a model for designing new immunomodulatory therapeutics.

PMID- 27028513
TI  - T4 lysozyme fused with cellulose-binding module for antimicrobial cellulosic
      wound dressing materials.
AB  - AIMS: Bacterial infection is a major challenge in wound care. Antimicrobial wound
      dressings are of great value for treating wound infections. Endolysins are
      evolving as a new class of antimicrobials with multiple applications. This study
      describes the production and evaluation of T4 lysozyme (T4Lyz), product of gene e
      of the T4 bacteriophage, fused with Cellulose Binding Module (CBM) for facile
      immobilization to cellulosic wound dressing. METHODS AND RESULTS: Genes encoding
      T4Lyz-CBM and T4Lyz were cloned and expressed in Escherichia coli and the enzymes
      were purified by cation exchange chromatography. While the CBM tag did not alter
      the optimum pH and stability features of T4Lyz, the lytic activity of the fusion
      protein was lowered. The bactericidal activity of T4Lyz-CBM, determined by viable
      count plating assay after 1 h incubation with Micrococcus lysodeikticus was 97.5%
      with 10 MUg ml(-1) , and 99.96% and 95% for E. coli and Pseudomonas mendocina,
      respectively, with 200 MUg ml(-1) enzyme. T4Lyz-CBM was immobilized to wound
      dressing gauze with a capacity of 5.5 MUg mg(-1) matrix, whereas the unmodified
      T4Lyz did not exhibit any binding. The immobilized protein retained its
      bactericidal activity against Gram-positive and Gram-negative bacteria. Both free
      and immobilized T4Lyz-CBM, after heat denaturation, retained their bactericidal
      activities against Gram-negative bacteria only. The immobilized enzyme exhibited
      higher stability than the free enzyme when stored in dry form or in the presence
      of polyol stabilizers. CONCLUSION: Tagging T4Lyz with CBM provides a facile,
      irreversible binding to cellulosic wound dressing while retaining its activity.
      This approach may be suitable even for other antimicrobial enzymes and -peptides.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The spread of antibiotic resistance
      requires innovative strategies for discovery and development of effective
      antimicrobial alternatives. This report presents a novel strategy for producing
      antimicrobial wound dressing materials.

PMID- 27028512
TI  - Genetic Evaluation of Schizophrenia Using the Illumina HumanExome Chip.
AB  - INTRODUCTION: Schizophrenia is a genetically heterogeneous disorder that is
      associated with several common and rare genetic variants. As technology involved,
      cost advantages of chip based genotyping was combined with information about rare
      variants, resulting in the Infinium HumanExome Beadchip. Using this chip, a
      sample of 493 patients with schizophrenia or schizoaffective disorder and 484
      healthy controls was genotyped. RESULTS: From the initial 242901 SNVs, 88306 had
      at least one minor allele and passed quality control. No variant reached
      genomewide-significant results (p<10(-8)). The SNP with the lowest p-value was
      rs1230345 in WISP3 (p = 3.05*10(-6)), followed by rs9311525 in CACNA2D3 (p =
      1.03*10(-5)) and rs1558557 (p = 3.85*10(-05)) on chromosome 7. At the gene level,
      3 genes were of interest: WISP3, on chromosome 6q21, a signally protein from the
      extracellular matrix. A second candidate gene is CACNA2D3, a regulator of the
      intracerebral calcium pathway. A third gene is TNFSF10, associated with p53
      mediated apoptosis.

PMID- 27028514
TI  - Chikungunya virus, risks and responses for Australia.

PMID- 27028515
TI  - Astragalar Morphology of Selected Giraffidae.
AB  - The artiodactyl astragalus has been modified to exhibit two trochleae, creating a
      double pullied structure allowing for significant dorso-plantar motion, and
      limited mediolateral motion. The astragalus structure is partly influenced by
      environmental substrates, and correspondingly, morphometric studies can yield
      paleohabitat information. The present study establishes terminology and describes
      detailed morphological features on giraffid astragali. Each giraffid astragalus
      exhibits a unique combination of anatomical characteristics. The giraffid
      astragalar morphologies reinforce previously established phylogenetic
      relationships. We find that the enlargement of the navicular head is a feature
      shared by all giraffids, and that the primitive giraffids possess exceptionally
      tall astragalar heads in relation to the total astragalar height. The sivatheres
      and the okapi share a reduced notch on the lateral edge of the astragalus. We
      find that Samotherium is more primitive in astragalar morphologies than
      Palaeotragus, which is reinforced by tooth characteristics and ossicone position.
      Diagnostic anatomical characters on the astragalus allow for giraffid species
      identifications and a better understanding of Giraffidae. 

PMID- 27028516
TI  - Quercetin Partially Preserves Development of Osteoblast Phenotype in Fetal Rat
      Calvaria Cells in an Oxidative Stress Environment.
AB  - Studies are needed to improve understanding of the osteoblast antioxidant
      response, and the balance between oxidative homeostasis and osteoblast
      differentiation. The flavonol quercetin aglycone (QRC) up-regulates the
      osteoblast antioxidant response in vitro without suppressing osteoblast
      phenotype, suggesting that QRC may preserve osteoblast phenotypic development in
      cells subsequently exposed to oxidative stress, which suppresses osteoblast
      differentiation. The aims of this study were to assess the extent that QRC
      pretreatment preserved development of the osteoblast phenotype in cells
      subsequently cultured with hydrogen peroxide, an oxidative stressor, and to
      characterize alterations in the osteoblast antioxidant response and in key
      antioxidant signaling pathways. We hypothesized that pretreatment with QRC would
      preserve phenotypic development after hydrogen peroxide treatment, suppress the
      hydrogen peroxide-induced antioxidant response, and that the antioxidant response
      would involve alterations in Nrf2 and ERK1/2 signaling. Results showed that
      treating fetal rat calvarial osteoblasts for 4 days (D5-9) with 300 MUM hydrogen
      peroxide resulted in fewer alkaline phosphatase-positive cells and mineralized
      nodules, altered cell morphology, and significantly lower osteoblast phenotypic
      gene expression (P < 0.05). This suppression was partially blocked when cells
      were pretreated 12 h with 20 MUM QRC. Hydrogen peroxide also produced sustained
      up-regulation of heme oxygenase-1 (HO-1) and gamma-glutamate cysteine ligase
      catalytic subunit (GCLC), which was partially blocked in hydrogen peroxide
      treated cells that first received QRC pretreatment. The alterations in the
      antioxidant stress response coincided with alterations in phosphorylated ERK1/2,
      but not Nrf2. These results suggest that QRC suppresses hydrogen peroxide-induced
      activation of the antioxidant response, and partially preserves osteoblast
      phenotypic development. J. Cell. Physiol. 231: 2779-2788, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27028517
TI  - Detection of Circulating Tumor DNA in Human Blood via DNA-Mediated Surface
      Enhanced Raman Spectroscopy of Single-Walled Carbon Nanotubes.
AB  - The levels of circulating tumor DNA (ctDNA) in the peripheral blood have been
      associated with tumor burden and malignant progression. However, ultrasensitive
      detection of ctDNA in blood remains to be explored. Herein, we have developed a
      new approach, employing DNA-mediated surface-enhanced Raman scattering (SERS) of
      single-walled carbon nanotubes (SWNTs), that allows ultrasensitive detection of a
      broad range of ctDNAs in human blood. Combined with the efficient ctDNA
      recognition capacity of our designed triple-helix molecular switch and RNase HII
      enzyme-assisted amplification, the T-rich DNA-mediated SERS enhancement of SWNTs
      could read out a content of KRAS G12DM as low as 0.3 fM, with a detection of 5.0
      MUL of sample volume, which has potential for point-of-care testing in clinical
      analysis.

PMID- 27028519
TI  - Diversity.

PMID- 27028520
TI  - Cardioversion of Atrial Fibrillation in ENGAGE AF-TIMI 48.

PMID- 27028521
TI  - The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for
      pH-Dependent Entry into Bat but Not Human Cells.
AB  - New World bats have recently been discovered to harbor influenza A virus (FLUAV)
      related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The
      internal proteins of batFLUAV are functional in mammalian cells. In contrast, no
      biological functionality could be demonstrated for the surface proteins,
      hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these
      proteins need to be replaced by their human counterparts to allow spread of
      batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role
      of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL
      were able to enter bat cells but not cells from other mammalian species. Host
      cell entry was mediated by HAL and was dependent on prior proteolytic activation
      of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL
      driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able
      to activate HAL for cell entry indicating that batFLUAV can utilize human
      proteases for HAL activation. Collectively, these results identify viral and
      cellular factors governing host cell entry driven by batFLUAV surface proteins.
      They suggest that the absence of a functional receptor precludes entry of
      batFLUAV into human cells while other prerequisites for entry, HAL activation and
      protonation, are met in target cells of human origin. 

PMID- 27028522
TI  - Internal jugular vein/common carotid artery cross-sectional area ratio and
      central venous pressure.
AB  - PURPOSE: To investigate the accuracy of the sonographic assessment of internal
      jugular vein/common carotid artery (IJV/CCA) cross-sectional area ratio in
      predicting central venous pressure (CVP) in critically ill patients. METHODS: In
      adult patients who underwent central venous catheterization for monitoring of
      hemodynamic status, we used bedside sonography for diameter and cross-sectional
      area measurement of IJV and CCA. The IJV/CCA ratio was then calculated, and its
      correlation with CVP as well as its sensitivity, specificity, and positive and
      negative predictive values were analyzed. RESULTS: We enrolled 52 patients with a
      mean age of 58.8 +/- 10.7 years. The mean IJV/CCA ratio was 1.89 +/- 0.83 and
      1.90 +/- 0.83, respectively, at inspiration and expiration. A significant
      correlation was observed between IJV/CCA ratio and CVP (r = 0.728, p < 0.0001 at
      inspiration, and r = 0.736, p < 0.0001 at expiration). Sensitivity was 90%,
      specificity 86.36%, positive predictive values 90%, and negative predictive
      values 86.36% for the prediction of CVP <10 cm H2 O. CONCLUSIONS: Assessing the
      IJV/CCA ratio with a portable sonographic device could be a noninvasive
      alternative for central venous catheterization in order to evaluate the
      hemodynamic status of critically ill patients. (c) 2016 Wiley Periodicals, Inc. J
      Clin Ultrasound 44:312-318, 2016.

PMID- 27028524
TI  - High Performance Flexible Actuator of Urchin-Like ZnO
      Nanostructure/Polyvinylenefluoride Hybrid Thin Film with Graphene Electrodes for
      Acoustic Generator and Analyzer.
AB  - A bass frequency response enhanced flexible polyvinylidene fluoride (PVDF) based
      thin film acoustic actuator is successfully fabricated. High concentrations of
      various zinc oxide (ZnO) is embedded in PVDF matrix, enhancing the beta phase
      content and the dielectric property of the composite thin film. ZnO acts as a
      nucleation agent for the crystallization of PVDF. A chemical vapor deposition
      grown graphene is used as electrodes, enabling high electron mobility for the
      distortion free acoustic signals. The frequency response of the fabricated
      acoustic actuator is studied as a function of the film thickness and filler
      content. The optimized film has a thickness of 80 MUm with 30 wt% filler content
      and shows 72% and 42% frequency response enhancement in bass and midrange
      compared to the commercial PVDF, respectively. Also, the total harmonic
      distortion decreases to 82% and 74% in the bass and midrange regions,
      respectively. Furthermore, the composite film shows a promising potential for
      microphone applications. Most of all, it is demonstrated that acoustic actuator
      performance is strongly influenced by degree of PVDF crystalline.

PMID- 27028523
TI  - The tangled bank of amino acids.
AB  - The use of amino acid substitution matrices to model protein evolution has
      yielded important insights into both the evolutionary process and the properties
      of specific protein families. In order to make these models tractable, standard
      substitution matrices represent the average results of the evolutionary process
      rather than the underlying molecular biophysics and population genetics, treating
      proteins as a set of independently evolving sites rather than as an integrated
      biomolecular entity. With advances in computing and the increasing availability
      of sequence data, we now have an opportunity to move beyond current substitution
      matrices to more interpretable mechanistic models with greater fidelity to the
      evolutionary process of mutation and selection and the holistic nature of the
      selective constraints. As part of this endeavour, we consider how epistatic
      interactions induce spatial and temporal rate heterogeneity, and demonstrate how
      these generally ignored factors can reconcile standard substitution rate matrices
      and the underlying biology, allowing us to better understand the meaning of these
      substitution rates. Using computational simulations of protein evolution, we can
      demonstrate the importance of both spatial and temporal heterogeneity in
      modelling protein evolution.

PMID- 27028525
TI  - Galectin-7 in the stratum corneum: a biomarker of the skin barrier function.
AB  - OBJECTIVE: Skin barrier disruption often occurs in diseased and damaged skin
      conditions such as atopic dermatitis (AD). We focused the galectin-7 protein (Gal
      7) as a biomarker of skin condition and assessed whether the content of Gal-7 in
      stratum corneum (scGal-7) could be used as an indicator of skin barrier
      disruption and as an index of local skin symptoms in AD patients. METHODS:
      Alteration of Gal-7 expression levels in keratinocyte and scGal-7 contents after
      barrier disruption by sodium dodecyl sulphate were evaluated in vitro and in
      vivo, respectively. Correlation between scGal-7 content and transepidermal water
      loss (TEWL) was examined in 126 healthy subjects. We performed single
      measurements of scGal-7 contents in 34 AD patients and serial measurements of 15
      inpatients among them. SC samples were collected by the tape-stripping method,
      and scGal-7 content was determined using enzyme-linked immunosorbent assay.
      RESULTS: Gal-7 expression in keratinocytes increased after barrier disruption.
      The scGal-7 content reflected the disruption of the skin barrier. The scGal-7
      contents and TEWL values correlated in healthy subjects. The scGal-7 level was
      higher in AD patients than in healthy subjects. The scGal-7 contents in the cheek
      and neck of AD patients significantly correlated with the total and local skin
      lesion severity scores. Serial measurements in the inpatients showed that the
      scGal-7 contents in the cheek and neck decreased in tandem with local severity
      scores in response to treatment. CONCLUSION: Measurement of scGal-7 content in
      tape-stripped samples was useful for the evaluation of the skin barrier function
      in dry skin conditions such as AD.

PMID- 27028526
TI  - Biomechanical, micro-computed tomographic and immunohistochemical analysis of
      early osseous integration at titanium implants placed following lateral ridge
      augmentation using extracted tooth roots.
AB  - OBJECTIVES: To assess biomechanical, micro-computed tomographic (micro CT) and
      immunohistochemical characteristics of early osseous integration at titanium
      implants placed following lateral ridge augmentation using autogenous extracted
      tooth roots. MATERIAL & METHODS: The roots of healthy maxillary premolars (PM)
      and retromolar cortical autogenous bone (AB) blocks were used for lateral ridge
      augmentation at chronic-type defects in the lower quadrants of n = 16 foxhounds.
      At 12 weeks, titanium implants were inserted and left to heal for another 3
      weeks. Osteocalcin (OC) antigen reactivity, removal torque values (RT) and the
      bone volume per tissue volume (micro CT- BV/TV) along the implants were assessed.
      RESULTS: Median OC (PM: 6.71 vs. AB: 2.73%), RT (PM: 61.97 vs. AB: 44.8 Ncm) and
      BV/TV (PM: 0.34 vs. AB: 0.21) values were comparable in both PM and AB groups.
      CONCLUSIONS: PM and AB grafted sites equally supported the early stages of
      osseointegration.

PMID- 27028527
TI  - Cholesteroloma: a rare thymic pseudotumor.

PMID- 27028528
TI  - Esthesioneuroblastoma with bilateral metastases to the parotid glands.
AB  - BACKGROUND: Esthesioneuroblastoma (ENB) is a rare, poorly characterized,
      intranasal cancer arising from olfactory neuroepithelium. METHODS: This case
      report reviews the underlying pathophysiology, clinical presentation, and
      diagnosis of primary ENB and parotid metastases. RESULTS: We present the case of
      a 43-year-old man who was referred to our practice with radiographically and
      biopsy confirmed ENB. After neoadjuvant chemotherapy, radiation, and open
      surgical resection, he returned to the clinic 30 months postoperatively with a
      right parotid mass, which was found to be a recurrence of his primary cancer. A
      parotidectomy was performed; however, he returned 10 months later with a new left
      parotid mass. Subsequent imaging and biopsy confirmed recurrence of ENB and a
      second parotidectomy was performed. CONCLUSION: This case illustrates that
      delayed metastases in the setting of ENB are not limited to the cervical lymph
      nodes and, in rare instances, may involve the parotid glands. Surveillance should
      include the parotid lymph node basin with a high clinical index of suspicion in
      the setting of parotid lymphadenopathy after primary surgical therapy. (c) 2016
      Wiley Periodicals, Inc. Head Neck 38: E2457-E2460, 2016.

PMID- 27028530
TI  - Validation of an Enhanced Version of a Single-Nucleotide Polymorphism-Based
      Noninvasive Prenatal Test for Detection of Fetal Aneuploidies.
AB  - OBJECTIVE: To validate an updated version (Version 2) of a single-nucleotide
      polymorphism (SNP)-based noninvasive prenatal test (NIPT) and to determine the
      likelihood of success when testing for fetal aneuploidies following a redraw.
      METHODS: Version 2 was analytically validated using 587 plasma samples with known
      genotype (184 trisomy 21, 37 trisomy 18, 15 trisomy 13, 9 monosomy X, 4 triploidy
      and 338 euploid). Sensitivity, specificity and no-call rate were calculated, and
      a fetal-fraction adjustment was applied to enable projection of these values in a
      commercial distribution. Likelihood of success of a second blood draw was
      computed based on fetal fraction and maternal weight from the first draw.
      RESULTS: Validation of this methodology yielded high sensitivities (>=99.4%) and
      specificities (100%) for all conditions tested with an observed no-call rate of
      2.3%. The no-call threshold for sample calling was reduced to 2.8% fetal
      fraction. The redraw success rate was driven by higher initial fetal fractions
      and lower maternal weights, with the fetal fraction being the more significant
      variable. CONCLUSIONS: The enhanced version of this SNP-based NIPT method showed
      a reduced no-call rate and a reduced fetal-fraction threshold for sample calling
      in comparison to the earlier version, while maintaining high sensitivity and
      specificity.

PMID- 27028531
TI  - The medico-legal value of consensus statements.

PMID- 27028532
TI  - Non-sclerotic bone involvement in Erdheim-Chester: PET/CT and MRI findings in a
      15-year-old boy.
AB  - Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis with
      multi-organ infiltration that occurs mainly in adults. Pediatric cases are
      extremely rare. Here we report a case of multisystemic Erdheim-Chester disease in
      a 15-year-old boy with central nervous system involvement and skeletal findings.
      Positron emission tomography (PET) and MRI were used to demonstrate
      characteristic bilateral, symmetrical medullary involvement of the metadiaphyses
      of long bones in the absence of the classic sclerotic radiographic appearance.
      This illustrates the potential for earlier diagnosis and visualization of
      therapeutic response in children. 

PMID- 27028533
TI  - Radiation exposure contribution of the scout abdomen radiograph in common
      pediatric fluoroscopic procedures.
AB  - BACKGROUND: Contrast enema, voiding cystourethrography and upper gastrointestinal
      studies are the most common fluoroscopic procedures in children. Scout abdomen
      radiographs have been routinely obtained prior to fluoroscopy and add to the
      radiation exposure from these procedures. Elimination of unnecessary routine
      scout radiographs in select studies might significantly reduce radiation exposure
      to children and improve the overall benefit-to-risk ratio of these fluoroscopic
      procedures. OBJECTIVE: To determine the radiation exposure contribution of the
      preliminary/scout abdomen radiographs with respect to the radiation exposure of
      the total procedure. MATERIALS AND METHODS: We retrospectively collected
      demographic information and radiation exposure values of dose area product (in Gy
      cm(2)) and entrance air kerma (in mGy) - initially for the scout abdomen
      radiographs done prior to fluoroscopy and subsequently the total procedural
      radiation values (the combined values of the scout radiograph and fluoroscopic
      radiation exposure) - in children who underwent contrast enemas, voiding
      cystourethrograms and upper gastrointestinal studies in a 4-month period. The
      radiation parameters, including fluoroscopy time, dose area product and entrance
      air kerma, were available in the log book maintained in the fluoroscopy suite.
      Fluoroscopy procedures were performed on a single fluoroscopy machine using four
      frames per second pulse rate and other radiation-minimizing techniques. Usage of
      the grid to obtain scout radiographs was also recorded. The proportion of
      radiation exposure from the scout radiograph relative to that of the total
      procedure was calculated by dividing the individual parameters of the scout to
      the total procedural values and multiplied by 100 to express these values as a
      percentage. We calculated mean, median and range and performed statistical
      analysis of the data. RESULTS: A total of 151 procedures performed on 71 males
      and 80 females qualified for the study. The age range of the patients was 2 days
      to 18 years, with a mean of nearly 3.5 years (40 months) and median of 15 months.
      There were 63 upper gastrointestinal studies, 65 voiding cystourethrography
      studies and 23 contrast enema studies. The fluoroscopy time for all procedures
      combined ranged from 0.1 min (6 s) to 2 min, with mean and median values of 0.4
      min and 0.3 min, respectively. The fractional radiation exposure contribution for
      the dose area product of scout abdomen radiograph to the total procedure ranged
      from 4% to 98%, with mean and median values of 51% and 49%, respectively. The
      fractional contribution of the scout radiograph to the total procedure for the
      entrance air kerma values ranged from 6% to 97%, with mean and median values of
      29% and 26%, respectively. There was a significant negative correlation (P<0.001)
      between fluoroscopy radiation time and the proportion of radiation parameters of
      scout radiograph to total procedural values. CONCLUSION: Scout radiographs can
      contribute a significant proportion (median values of approximately 50% for the
      dose area product and 26% for the entrance air kerma) of radiation exposure in
      common fluoroscopy procedures in children.

PMID- 27028534
TI  - [Tracing the neurobiological causes of chronic pain].

PMID- 27028536
TI  - The Gastrointestinal Tract Microbiota and Allergic Diseases.
AB  - The gastrointestinal (GI) tract microbiota is required for optimal digestion of
      foods, for the development of resistance against pathogens (termed colonization
      resistance), for the development of mucosa-associated lymphoid tissue, and for
      local as well as systemic immune homeostasis. Certain constituents of the GI
      tract microbiota are widely recognized as critical regulators and modulators of
      their host's immune response. These include bacterial members of the microbiota
      as well as parasitic nematodes. Immune regulation by immunomodulatory members of
      the GI microbiota primarily serves to subvert host antimicrobial immune defenses
      and promote persistent colonization, but as a side effect may prevent or suppress
      immunological disorders resulting from inappropriate responses to harmless
      antigens, such as allergy, colitis or autoimmunity. Many of the best understood
      GI-resident immunomodulatory species have co-evolved with their mammalian hosts
      for tens of thousands of years and masterfully manipulate host immune responses.
      In this review, we discuss the epidemiological evidence for the role of the GI
      tract microbiota as a whole, and of specific members, in protection against
      allergic and other immunological disorders. We then focus on the mechanistic
      basis of microbial immunomodulation, which is presented using several well
      understood paradigmatic examples, that is, helminths, Helicobacter pylori,
      Bifidobacteria and Lactobacilli. In a final chapter, we highlight past and
      ongoing attempts at harnessing the immunomodulatory properties of GI microbiota
      species and their secreted products for intervention studies and describe the
      promises and limitations of these experimental approaches. The effects of pro-
      and prebiotics, bacterial lysates, as well as of fecal microbiota transplantation
      are presented and compared. 

PMID- 27028537
TI  - The influence of different maternal pushing positions on birth outcomes at the
      second stage of labor in nulliparous women.
AB  - OBJECTIVES: To assess the effects on neonatal and maternal outcomes of different
      pushing positions during the second stage of labor in nulliparous women. METHODS:
      This prospective study included 102 healthy, pregnant, nulliparous women who were
      randomly allocated to either of two positions: a squatting using bars (n = 51),
      or a supine position modified to 45 degree of semi-fowler (n = 51) during the
      second stage of labor. Duration of the second stage of labor, maternal pain,
      postpartum blood loss, abnormal fetal heart rate patterns that required
      intervention, and newborn outcomes were compared between the two groups. RESULTS:
      The trial showed that women who adopted the squatting position using bars
      experienced a significant reduction in the duration of the second stage of labor;
      they were less likely to be induced, and their Visual Analog Scale score was
      lower than those who were allocated the supine position modified to 45 degree of
      semi-fowler during second stage of labor (p < 0.05). There were no significant
      differences with regard to postpartum blood loss, neonatal birth weight, Apgar
      score at one and five minutes, or admission to the Neonatal Intensive Care Unit.
      CONCLUSIONS: In healthy nulliparous women, adopting a squatting position using
      bars was associated with a shorter second stage of labor, lower Visual Analog
      Scale score, more satisfaction, and a reduction in oxytocin requirements compared
      with adopting the supine position. For Turkish women, the squatting position is
      easy to adopt as it is more appropriate in terms of Turkish social habits and
      traditions.

PMID- 27028535
TI  - Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in
      Anesthesia and Pain Therapy.
AB  - Ketamine is a phencyclidine derivative, which functions primarily as an
      antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma
      aminobutyric acid receptors in the central nervous system. Ketamine shows a
      chiral structure consisting of two optical isomers. It undergoes oxidative
      metabolism, mainly to norketamine by cytochrome P450 (CYP) 3A and CYP2B6 enzymes.
      The use of S-ketamine is increasing worldwide, since the S(+)-enantiomer has been
      postulated to be a four times more potent anesthetic and analgesic than the R(-)
      enantiomer and approximately two times more effective than the racemic mixture of
      ketamine. Because of extensive first-pass metabolism, oral bioavailability is
      poor and ketamine is vulnerable to pharmacokinetic drug interactions. Sublingual
      and nasal formulations of ketamine are being developed, and especially nasal
      administration produces rapid maximum plasma ketamine concentrations with
      relatively high bioavailability. Ketamine produces hemodynamically stable
      anesthesia via central sympathetic stimulation without affecting respiratory
      function. Animal studies have shown that ketamine has neuroprotective properties,
      and there is no evidence of elevated intracranial pressure after ketamine dosing
      in humans. Low-dose perioperative ketamine may reduce opioid consumption and
      chronic postsurgical pain after specific surgical procedures. However, long-term
      analgesic effects of ketamine in chronic pain patients have not been
      demonstrated. Besides analgesic properties, ketamine has rapid-acting
      antidepressant effects, which may be useful in treating therapy-resistant
      depressive patients. Well-known psychotomimetic and cognitive adverse effects
      restrict the clinical usefulness of ketamine, even though fewer psychomimetic
      adverse effects have been reported with S-ketamine in comparison with the
      racemate. Safety issues in long-term use are yet to be resolved.

PMID- 27028539
TI  - Lewis Acid Catalyzed Friedel-Crafts Alkylation of Alkenes with
      Trifluoropyruvates.
AB  - A Friedel-Crafts alkylation reaction of styrenes with trifluoropyruvates has been
      developed, which delivered allylic alcohols in excellent yields (up to 98%) using
      the Ni(ClO4)2.6H2O/bipyridine complex as a catalyst. The asymmetric reaction was
      catalyzed by the chiral Cu(OTf)2/bisoxazoline complex to afford the corresponding
      chiral allylic alcohols bearing trifluoromethylated quaternary stereogenic
      centers in moderate enantioselectivities (up to 75% ee).

PMID- 27028538
TI  - Plasma Membrane Repair Is Regulated Extracellularly by Proteases Released from
      Lysosomes.
AB  - Eukaryotic cells rapidly repair wounds on their plasma membrane. Resealing is
      Ca(2+)-dependent, and involves exocytosis of lysosomes followed by massive
      endocytosis. Extracellular activity of the lysosomal enzyme acid sphingomyelinase
      was previously shown to promote endocytosis and wound removal. However, whether
      lysosomal proteases released during cell injury participate in resealing is
      unknown. Here we show that lysosomal proteases regulate plasma membrane repair.
      Extracellular proteolysis is detected shortly after cell wounding, and inhibition
      of this process blocks repair. Conversely, surface protein degradation
      facilitates plasma membrane resealing. The abundant lysosomal cysteine proteases
      cathepsin B and L, known to proteolytically remodel the extracellular matrix, are
      rapidly released upon cell injury and are required for efficient plasma membrane
      repair. In contrast, inhibition of aspartyl proteases or RNAi-mediated silencing
      of the lysosomal aspartyl protease cathepsin D enhances resealing, an effect
      associated with the accumulation of active acid sphingomyelinase on the cell
      surface. Thus, secreted lysosomal cysteine proteases may promote repair by
      facilitating membrane access of lysosomal acid sphingomyelinase, which promotes
      wound removal and is subsequently downregulated extracellularly by a process
      involving cathepsin D.

PMID- 27028540
TI  - Gold(I)-Catalyzed Hydroaminaloxylation and Petasis-Ferrier Rearrangement Cascade
      of Aminaloalkynes.
AB  - An efficient method has been developed to generate a diverse array of
      indolizidines and quinolizidines from readily available aminaloalkynes via a
      gold(I)-catalyzed hydroaminaloxylation and Petasis-Ferrier rearrangement cascade.
      The method enabled a formal synthesis of (+/-)-antofine. 

PMID- 27028541
TI  - Structure-Based Sequence Alignment of the Transmembrane Domains of All Human
      GPCRs: Phylogenetic, Structural and Functional Implications.
AB  - The understanding of G-protein coupled receptors (GPCRs) is undergoing a
      revolution due to increased information about their signaling and the
      experimental determination of structures for more than 25 receptors. The
      availability of at least one receptor structure for each of the GPCR classes,
      well separated in sequence space, enables an integrated superfamily-wide analysis
      to identify signatures involving the role of conserved residues, conserved
      contacts, and downstream signaling in the context of receptor structures. In this
      study, we align the transmembrane (TM) domains of all experimental GPCR
      structures to maximize the conserved inter-helical contacts. The resulting
      superfamily-wide GpcR Sequence-Structure (GRoSS) alignment of the TM domains for
      all human GPCR sequences is sufficient to generate a phylogenetic tree that
      correctly distinguishes all different GPCR classes, suggesting that the class
      level differences in the GPCR superfamily are encoded at least partly in the TM
      domains. The inter-helical contacts conserved across all GPCR classes describe
      the evolutionarily conserved GPCR structural fold. The corresponding structural
      alignment of the inactive and active conformations, available for a few GPCRs,
      identifies activation hot-spot residues in the TM domains that get rewired upon
      activation. Many GPCR mutations, known to alter receptor signaling and cause
      disease, are located at these conserved contact and activation hot-spot residue
      positions. The GRoSS alignment places the chemosensory receptor subfamilies for
      bitter taste (TAS2R) and pheromones (Vomeronasal, VN1R) in the rhodopsin family,
      known to contain the chemosensory olfactory receptor subfamily. The GRoSS
      alignment also enables the quantification of the structural variability in the TM
      regions of experimental structures, useful for homology modeling and structure
      prediction of receptors. Furthermore, this alignment identifies structurally and
      functionally important residues in all human GPCRs. These residues can be used to
      make testable hypotheses about the structural basis of receptor function and
      about the molecular basis of disease-associated single nucleotide polymorphisms. 

PMID- 27028542
TI  - Are take-home naloxone programmes effective? Systematic review utilizing
      application of the Bradford Hill criteria.
AB  - BACKGROUND AND AIMS: Fatal outcome of opioid overdose, once detected, is
      preventable through timely administration of the antidote naloxone. Take-home
      naloxone provision directly to opioid users for emergency use has been
      implemented recently in more than 15 countries worldwide, albeit mainly as pilot
      schemes and without formal evaluation. This systematic review assesses the
      effectiveness of take-home naloxone, with two specific aims: (1) to study the
      impact of take-home naloxone distribution on overdose-related mortality; and (2)
      to assess the safety of take-home naloxone in terms of adverse events. METHODS:
      PubMed, MEDLINE and PsychINFO were searched for English-language peer-reviewed
      publications (randomized or observational trials) using the Boolean search query:
      (opioid OR opiate) AND overdose AND prevention. Evidence was evaluated using the
      nine Bradford Hill criteria for causation, devised to assess a potential causal
      relationship between public health interventions and clinical outcomes when only
      observational data are available. RESULTS: A total of 1397 records (1164 after
      removal of duplicates) were retrieved, with 22 observational studies meeting
      eligibility criteria. Due to variability in size and quality of the included
      studies, meta-analysis was dismissed in favour of narrative synthesis. From
      eligible studies, we found take-home naloxone met all nine Bradford Hill
      criteria. The additional five World Health Organization criteria were all either
      met partially (two) or fully (three). Even with take-home naloxone
      administration, fatal outcome was reported in one in 123 overdose cases (0.8%;
      95% confidence interval = 0.4, 1.2). CONCLUSIONS: Take-home naloxone programmes
      are found to reduce overdose mortality among programme participants and in the
      community and have a low rate of adverse events.

PMID- 27028543
TI  - Levels of immunoglobulin E specific to the major food allergen and chemokine (C-C
      motif) ligand (CCL)17/thymus and activation regulated chemokine and
      CCL22/macrophage-derived chemokine in infantile atopic dermatitis on Ishigaki
      Island.
AB  - Atopic dermatitis (AD) is a multifactorial T-helper (Th)2-mediated skin disease
      frequently associated with elevated serum immunoglobulin (Ig)E and food allergy
      is also a Th2- and IgE-mediated adverse immunological reaction. Our previous
      study indicated the relation of egg allergy history and disease severity of AD.
      Thus, the purpose of the study was to investigate the levels of IgE specific to
      major food allergens (egg, milk, wheat) and Th2 chemokines (chemokine [C-C motif]
      ligand [CCL]17/thymus and activation regulated chemokine [TARC] and
      CCL22/macrophage-derived chemokine [MDC]) and the relationship between them. A
      total of 743 nursery school children were enrolled. Dermatologist-based physical
      examination and a questionnaire survey were also conducted. Significantly
      increased levels of disease severity markers (CCL17/TARC and CCL22/MDC) were
      confirmed in children with AD. The levels of CCL22/MDC in all of the children
      were markedly high compared with those reported in adults. IgE specific to egg
      white, ovomucoid, wheat and mite antigen were significantly higher in the AD
      group than in the non-AD group. Among them, IgE specific to egg allergens were
      well associated with disease severity markers, and IgE specific to ovomucoid
      seemed particularly well correlated with the presence of egg allergy history. In
      conclusion, the markedly high level of CCL22/MDC in children as compared with
      those reported in adults may partly explain the AD-prone nature of children and
      their spontaneous remission afterwards. Mild but significant correlation of IgE
      specific to egg allergens and Th2 chemokines may explain correlation of disease
      severity and comorbidity of egg allergy in our previous study.

PMID- 27028544
TI  - Association of EPHB1 rs11918092 and EFNB2 rs9520087 with psychopathological
      symptoms of schizophrenia in Chinese Zhuang and Han populations.
AB  - Two single-nucleotide polymorphisms (SNPs) (rs11918092 and rs9520087) were
      genotyped in Chinese Zhuang and Han populations. Symptoms of schizophrenic
      patients were assessed by the Positive and Negative Syndrome Scale. No
      association of any SNP with schizophrenic susceptibility was found. However,
      associations of rs9520087 with the total scale score (P = 0.014), positive scale
      score (P = 0.013), negative scale score (P = 0.032), and general psychopathology
      scale score (P = 0.031) were found in Zhuang patients. Additionally, rs11918092
      was associated with positive scale score (P = 0.035) in Han patients. The two
      SNPs might influence symptoms of schizophrenia.

PMID- 27028545
TI  - Wide variation in estimates of global prevalence and burden of chronic hepatitis
      B and C infection cited in published literature.
AB  - To evaluate the extent of heterogeneity in global estimates of chronic hepatitis
      B (HBV) and C (HCV) cited in the published literature, we undertook a systematic
      review of the published literature. We identified articles from 2010 to 2014 that
      had cited global estimates for at least one of ten indicators [prevalence and
      numbers infected with HBV, HCV, HIV-HBV or HIV-HCV co-infection, and mortality
      (number of deaths annually) for HBV and HCV]. Overall, 488 articles were
      retrieved: 239 articles cited a HBV-related global estimate [prevalence (n = 12),
      number infected (n = 193) and number of annual deaths (n = 82)]; 280 articles had
      HCV-related global estimates [prevalence (n = 86), number infected (n = 203) and
      number of annual deaths (n = 31)]; 31 had estimates on both HBV and HCV; 54 had
      HIV-HBV co-infection estimates [prevalence (n = 42) and number co-infected (n =
      12)]; and 68 had estimates for HIV-HCV co-infection [prevalence (n = 40) and
      number co-infected (n = 28)]. There was considerable heterogeneity in the
      estimates cited and also a lack of consistency in the terminology used. Although
      40% of 488 articles cited WHO as the source of the estimate, many of these were
      from outdated or secondary sources. Our findings highlight the importance of
      clear and consistent communication from WHO and other global health agencies on
      current consensus estimates of hepatitis B and C burden and prevalence, the need
      for standardisation in their citation, and for regular updates.

PMID- 27028546
TI  - Changes in liver steatosis evaluated by transient elastography with the
      controlled attenuation parameter in HIV-infected patients.
AB  - OBJECTIVES: There are scant data on the progression of hepatic steatosis (HS) in
      HIV infection. We therefore evaluated changes in HS over time in HIV-infected
      patients using the controlled attenuation parameter (CAP). METHODS: A prospective
      cohort of 326 HIV-infected patients was included in this study. All patients
      underwent a CAP measurement. Changes in steatosis were evaluated by calculating
      the median (Q1-Q3) difference between baseline and 12-month CAP values. RESULTS:
      The median (Q1-Q3) CAP was 221 (196-252) dB/m at baseline and 224 (198-257) dB/m
      at the 12-month visit (P = 0.617). Significant steatosis, that is, CAP >= 238
      dB/m, was observed in 76 individuals (37%) at baseline and in 80 (39%) at the 12
      month visit (P = 0.683). The following variables were associated with DeltaCAP:
      plasma HIV RNA [< 50 vs. >= 50 HIV-1 RNA copies/mL: median (Q1-Q3) DeltaCAP, 4 (
      21, 27) vs. -21 (-49, 4) dB/m, respectively; P = 0.024]; body mass index (BMI)
      [no increase vs. increase: -13 (-40, 4) vs. 14 (-6, 32) dB/m, respectively; P <
      0.001]; triglycerides [no increase vs. increase: -1 (-30, 22) vs. 15 (-3, 40)
      dB/m, respectively; P = 0.001]; fasting plasma glucose [not impaired vs.
      impaired: -4 (-31, 16) vs. 30 (15, 49) dB/m, respectively; P < 0.001]; and
      raltegravir [no vs. yes: 5 (-20, 29) vs. -11 (-37.5, 15) dB/m, respectively; P =
      0.018]. The only factor independently associated with DeltaCAP was BMI [B
      (standard error): 9.03 (1.9); P < 0.001]. CONCLUSIONS: Increases in CAP values
      over a period of 12 months in HIV-infected patients were strongly associated with
      elevations in BMI. Other metabolic factors and antiretroviral drugs were not
      predictors of CAP changes independent of BMI.

PMID- 27028547
TI  - Anaplastic Carcinoma Arising in a Mucinous Cystic Neoplasm Masquerading as
      Pancreatic Pseudocyst.
AB  - Mucinous cystic neoplasms (MCN) of the pancreas can vary from benign to
      premalignant and malignant. Preoperative diagnosis is essential to offer the
      patient appropriate treatment. Occasionally these cases may harbor anaplastic
      carcinoma while clinically masquerade as a pseudocyst. Here in, we report an
      unusual case of a 37-year old female presented with recurrent abdominal pain that
      was suspected clinically and by imaging studies to have a pseudocyst. EUS-FNA
      with internal drainage of the cyst was performed. Cytological evaluation of the
      cyst fluid showed numerous inflammatory cells composed mainly of many neutrophils
      admixed with macrophages reminiscent of the usual pseudocyst content but there
      were scattered rare dyscohesive malignant cells which were highly pleomorphic
      with multinucleation. Immunostains on the cell block showed immunoreactivity of
      these cells including the multinucleated cells for Cam 5.2 and AE1/AE3 and
      focally for Ber-Ep4, Moc -31, and CA19-9. The subsequent resection confirmed the
      presence of anaplastic (undifferentiated) carcinoma (AC) arising in a MCN of the
      pancreas. Diagn. Cytopathol. 2016;44:538-542. (c) 2016 Wiley Periodicals, Inc. 

PMID- 27028548
TI  - Chromatin structure and pre-mRNA processing work together.
AB  - Chromatin is the natural context for transcription elongation. However, the
      elongating RNA polymerase II (RNAPII) is forced to pause by the positioned
      nucleosomes present in gene bodies. Here, we briefly discuss the current results
      suggesting that those pauses could serve as a mechanism to coordinate
      transcription elongation with pre-mRNA processing. Further, histone post
      translational modifications have been found to regulate the recruitment of
      factors involved in pre-mRNA processing. This view highlights the important
      regulatory role of the chromatin context in the whole process of the mature mRNA
      synthesis.

PMID- 27028549
TI  - MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese
      Mongolian Population.
AB  - In this study, polymorphisms of major histocompatibility complex class I chain
      related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene
      were investigated for 158 unrelated Chinese Mongolian subjects recruited from
      central Inner Mongolia Autonomous Region, northern China, by polymerase chain
      reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles,
      including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01
      (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common
      alleles. Significant global linkage disequilibrium (LD) was detected between HLA
      B and MICA, HLA-B and MICB, and MICA and MICB loci (all P < 0.000001). The most
      frequent haplotypes were HLA-B*51:01-MICA*009:01 (7.28%), HLA-B*58:01-MICB*008
      (6.96%), MICA*010-MICB*005:02 (13.92%) and HLA-B*58:01-MICA*002:01-MICB*008
      (6.96%). HLA-B-MICA haplotypes such as HLA-B*50:01-MICA*009:02 were associated
      with single MICB allele. Some HLA-B-MICA haplotypes were associated with multiple
      MICB alleles, including HLA-B*51:01-MICA*009:01. One novel MICB allele, MICB*031,
      was identified, which has possibly arisen from MICB*002:01 through single
      mutation event. We also confirmed the existence of a recently recognized MICA
      allele, MICA*073, whose ethnic origin has not been previously described. Genotype
      distributions at MICA, MICB and HLA-B were consistent with a neutrality model.
      Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic
      groups. Findings shown here are important from an anthropologic perspective and
      will inform future studies of the potential role of MIC genes in allogeneic organ
      transplantation and HLA-linked disease association in populations of related
      ancestry. 

PMID- 27028550
TI  - Ultrafine Au and Ag Nanoparticles Synthesized from Self-Assembled Peptide Fibers
      and Their Excellent Catalytic Activity.
AB  - The self-assembly of an amphiphilic peptide molecule to form nanofibers
      facilitated by Ag(+) ions was investigated. Ultrafine AgNPs (NPs=nanoparticles)
      with an average size of 1.67 nm were synthesized in situ along the fibers due to
      the weak reducibility of the -SH group on the peptide molecule. By adding NaBH4
      to the peptide solution, ultrafine AgNPs and AuNPs were synthesized with an
      average size of 1.35 and 1.18 nm, respectively. The AuNPs, AgNPs, and
      AgNPs/nanofibers all exhibited excellent catalytic activity toward the reduction
      of 4-nitrophenol, with turnover frequency (TOF) values of 720, 188, and 96 h(-1)
      , respectively. Three dyes were selected for catalytic degradation by the
      prepared nanoparticles and the nanoparticles showed selective catalysis activity
      toward the different dyes. It was a surprising discovery that the ultrafine AuNPs
      in this work had an extremely high catalytic activity toward methylene blue, with
      a reaction rate constant of 0.21 s(-1) and a TOF value of 1899 h(-1) . 

PMID- 27028551
TI  - Correction: Familial Clusters of HTLV-1-Associated Myelopathy/Tropical Spastic
      Paraparesis.

PMID- 27028552
TI  - Liver transplantation in Australia and New Zealand.
AB  - Liver transplantation (LT) in Australia and New Zealand began in 1985. Over this
      time until December 2014, LT took place in 3700 adults and 800 children. LT is
      regulated with 1 unit, supported by the government, per state or region.
      Currently approximately 270 transplants take place per year. Organ donation rates
      are moderate in Australia (17 per 1 million of population) but very low in New
      Zealand (11 per 1 million of population). All the units share organ donors for
      fulminant hepatic failure cases (status 1). Recipient listing criteria and organ
      allocation criteria are commonly agreed to via National and Trans-Tasman
      agreements, which are published online. Current survival rates indicate
      approximately 94% 1-year survival with median survival in adults of approximately
      20 years, whereas 75% of children are alive at 20 years. All units collaborate in
      research projects via the Australia and New Zealand Liver Transplant Registry and
      have published highly cited articles particularly on the prevention of hepatitis
      B virus recurrence. Outcomes for indigenous populations have also been analyzed.
      In conclusion, LT in Australia and New Zealand is well developed with transparent
      processes related to criteria for listing and organ allocation together with
      publication of outcomes. Liver Transplantation 22 830-838 2016 AASLD.

PMID- 27028553
TI  - Organic Semiconductors based on Dyes and Color Pigments.
AB  - Organic dyes and pigments constitute a large class of industrial products. The
      utilization of these compounds in the field of organic electronics is reviewed
      with particular emphasis on organic field-effect transistors. It is shown that
      for most major classes of industrial dyes and pigments, i.e., phthalocyanines,
      perylene and naphthalene diimides, diketopyrrolopyrroles, indigos and isoindigos,
      squaraines, and merocyanines, charge-carrier mobilities exceeding 1 cm(2) V(-1)
      s(-1) have been achieved. The most widely investigated molecules due to their n
      channel operation are perylene and naphthalene diimides, for which even values
      close to 10 cm(2) V(-1) s(-1) have been demonstrated. The fact that all of these
      pi-conjugated colorants contain polar substituents leading to strongly
      quadrupolar or even dipolar molecules suggests that indeed a much larger
      structural space shows promise for the design of organic semiconductor molecules
      than was considered in this field traditionally. In particular, because many of
      these dye and pigment chromophores demonstrate excellent thermal and (photo
      )chemical stability in their original applications in dyeing and printing, and
      are accessible by straightforward synthetic protocols, they bear a particularly
      high potential for commercial applications in the area of organic electronics. 

PMID- 27028554
TI  - Integration of multi-objective structural optimization into cementless hip
      prosthesis design: Improved Austin-Moore model.
AB  - A new strategy of multi-objective structural optimization is integrated into
      Austin-Moore prosthesis in order to improve its performance. The new resulting
      model is so-called Improved Austin-Moore. The topology optimization is considered
      as a conceptual design stage to sketch several kinds of hollow stems according to
      the daily loading cases. The shape optimization presents the detailed design
      stage considering several objectives. Here, A new multiplicative formulation is
      proposed as a performance scale in order to define the best compromise between
      several requirements. Numerical applications on 2D and 3D problems are carried
      out to show the advantages of the proposed model. 

PMID- 27028555
TI  - Midwestern Association of Plastic Surgeons 2016, "Problem Solving in Plastic
      Surgery": Abstracts.

PMID- 27028556
TI  - Refractory Subcutaneous Sweet Syndrome Treated With Adalimumab.

PMID- 27028557
TI  - The fecal incontinence quality of life scale (FIQL) and fecal incontinence
      severity index (FISI): Validation of the Dutch versions.
AB  - AIMS: Fecal incontinence (FI) is known to have a major impact on quality of life.
      The Fecal Incontinence Quality of Life scale (FIQL) and Fecal Incontinence
      Severity Index (FISI) have been developed to assess this impact. The aim of this
      study was to validate the FIQL and FISI in the Dutch language. METHODS: The study
      population consisted of women and men experiencing FI and a reference group. The
      FIQL (four domains) and FISI questionnaires were validated by testing
      standardized measurement properties: discriminative ability, internal
      consistency, reproducibility, construct validity, and responsiveness. RESULTS: A
      total of 55 patients and 277 reference participants were included. Patients had
      significant lower and higher scores at the FIQL and FISI, respectively, than
      references (FIQL: 2.58 +/- 0.70 and 3.92 +/- 0.36, FISI: 38.57 +/- 10.73 and
      23.17 +/- 15.01; P < 0.001), indicating worse functioning in patients and with
      this the discriminative abilities of the measures. The FIQL demonstrated adequate
      internal consistency on all domains (0.72-0.96), except for the embarrassment
      domain (0.55). The reproducibility was good for both measures. A negative
      correlation was found between the FIQL and FISI. Furthermore, the FIQL showed a
      positive (0.77) and the FISI a negative correlation (-0.31) with the Mental
      Component Summary scale of the SF-12. Responsiveness analysis showed a minimal
      important change of 0.40 points for the FIQL. CONCLUSIONS: Validity and
      reliability were good in the Dutch FIQL, but inconclusive in the FISI. The Dutch
      FIQL can support physicians in determining the impact of FI on patient's quality
      of life. Neurourol. Urodynam. 36:710-715, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028558
TI  - Direct Imprinting of Liquid Silicon.
AB  - A polymeric precursor solution for semiconducting silicon called "liquid silicon"
      was synthesized and directly imprinted to form well-defined and fine amorphous
      silicon patterns. The spin-coated film was cured and imprinted followed by
      annealing at 380  degrees C to complete the polymer-to-silicon conversion. A
      pattern with dimensions of several hundreds of nanometers or less was obtained on
      a substrate. We demonstrated that the curing step before imprinting is
      particularly important in the imprinting process. A curing temperature of 140-180
      degrees C was found to be optimal in terms of the film's deformability and
      molding properties. Fourier transform infrared spectroscopy and thermal analysis
      clarified that the cross-linking of the polymer due to the 1,2-hydrogen shift
      reaction was induced exponentially with the release of a large amount of SiH4/H2
      gases at temperatures between 140 and 220  degrees C, leading to the
      solidification of the film. Consequently, the film completely lost its
      deformability at higher temperatures. Despite a volume shrinkage as large as 53
      56% during the polymer-to-silicon conversion, well-defined angular patterns were
      preserved. Fine silicon patterns were formed via the direct imprinting of liquid
      silicon with high resolution and high throughput, demonstrating the usefulness of
      this technique for the future manufacturing of silicon electronics. 

PMID- 27028559
TI  - Evaluation of Eu(II) -based positive contrast enhancement after intravenous,
      intraperitoneal, and subcutaneous injections.
AB  - Eu(II) -based contrast agents offer physiologically relevant, metal-based redox
      sensing that is unachievable with Gd(III) -based contrast agents. To evaluate the
      in vivo contrast enhancement of Eu(II) as a function of injection type, we
      performed intravenous, intraperitoneal, and subcutaneous injections in mice. Our
      data reveal a correlation between reported oxygen content and expected rates of
      diffusion with the persistence of Eu(II) -based contrast enhancement.
      Biodistribution studies revealed europium clearance through the liver and kidneys
      for intravenous and intraperitoneal injections, but no contrast enhancement was
      observed in organs associated with clearance. These data represent a step toward
      understanding the behavior of Eu(II) -based complexes in vivo. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27028560
TI  - Health claims using the term 'sustained energy' are trending but glycaemic
      response data are being used to support: is this misleading without context?
AB  - One of the most recent food trends is the quest for products that provide
      'sustained energy'; a term that is garnering considerable attention within the
      marketplace. Often, 'sustained energy' health claims are based on a food's post
      prandial glycaemic response. However, are generalised health claims regarding
      'sustained energy' valid when only supported by glycaemic response data? Without
      context, the short answer is: probably not. Health claims that link sustained
      energy to a glycaemic response, or any other attribute of a food or diet, require
      context to ensure that the public correctly interprets and experiences the
      claimed effect and is not misled in their quest for healthy foods that impose the
      desired physiological benefit.

PMID- 27028561
TI  - Zika Virus.

PMID- 27028562
TI  - Biological activities of Zn(II)-S-methyl-cysteine complex as antiradical,
      inhibitor of acid phosphatase enzyme and in vivo antidepressant effects.
AB  - The antidepressant effect of simple Zn(II) salts has been proved in several
      animal models of depression. In this study, a coordination metal complex of
      Zn(II) having a sulfur containing ligand is tested as antidepressant for the
      first time. Forced swimming test method on male Wistar rats shows a decrease in
      the immobility and an increase in the swimming behavior after treatment with
      [Zn(S-Met)2] (S-Met=S-methyl-l-cysteine) being more effective and remarkable than
      ZnCl2. The thiobarbituric acid and the pyranine consumption (hydroxyl and peroxyl
      radicals, respectively) methods were applied to evaluate the antioxidant activity
      of S-Met and [Zn(S-Met)2] showing evidence of attenuation of hydroxyl but not
      peroxyl radicals activities. UV-vis studies on the inhibition of acid phosphatase
      enzyme (AcP) demonstrated that S-methyl-l-cysteine did not produce any effect
      but, in contrast, [Zn(S-Met)2] complex behaved as a moderate inhibitor. Finally,
      bioavailability studies were performed by fluorescence spectroscopy denoting the
      ability of the albumin to transport the complex. 

PMID- 27028563
TI  - Singly versus Doubly Reduced Nickel Porphyrins for Proton Reduction: Experimental
      and Theoretical Evidence for a Homolytic Hydrogen-Evolution Reaction.
AB  - A nickel(II) porphyrin Ni-P (P=porphyrin) bearing four meso-C6 F5 groups to
      improve solubility and activity was used to explore different hydrogen-evolution
      reaction (HER) mechanisms. Doubly reduced Ni-P ([Ni-P](2-) ) was involved in H2
      production from acetic acid, whereas a singly reduced species ([Ni-P](-) )
      initiated HER with stronger trifluoroacetic acid (TFA). High activity and
      stability of Ni-P were observed in catalysis, with a remarkable ic /ip value of
      77 with TFA at a scan rate of 100 mV s(-1) and 20  degrees C. Electrochemical,
      stopped-flow, and theoretical studies indicated that a hydride species [H-Ni-P]
      is formed by oxidative protonation of [Ni-P](-) . Subsequent rapid bimetallic
      homolysis to give H2 and Ni-P is probably involved in the catalytic cycle. HER
      cycling through this one-electron-reduction and homolysis mechanism has been
      proposed previously but rarely validated. The present results could thus have
      broad implications for the design of new exquisite cycles for H2 generation.

PMID- 27028564
TI  - Medium density fibreboard production by hot pressing without adhesive using
      Triarrhena sacchariflora residue bio-pretreated by white-rot fungus Coriolus
      versicolor.
AB  - AIMS: To produce fibreboard with Triarrhena sacchariflora residue (TSR) without
      adhesive and understand the relationship between bio-pretreatment and mechanical
      property of fibreboard. METHODS AND RESULTS: White-rot fungus Coriolus versicolor
      was used to pretreat TSR, and biochemical and physical analysis were investigated
      by ultraviolet spectrophotometry, Fourier transform infrared spectroscopy and
      environmental scanning electron microscopy method. CONCLUSIONS: TSR was suitable
      to produce fibreboard without adhesive by bio-pretreatment with C. versicolor.
      The property of fibreboard became stronger by optimization of bio-pretreatment
      parameters, and the moduli of rupture and elasticity of fibreboard were increased
      to 18.12 MPa and 4.3 GPa, respectively, which were close to national standard of
      medium-density fibreboard with adhesive. Bio-pretreated TSR increased the
      mechanical properties of fibreboard because of 1.4-fold content of polysaccharide
      and 1.15 U g(-1) laccase, more hydroxyl group and more porous surface structure
      than that of untreated TSR. SIGNIFICANCE AND IMPACT OF THE STUDY: TSR-based
      fibreboard production without adhesive eliminated potential formaldehyde gas
      emission.

PMID- 27028565
TI  - Design and control of a novel gastroscope intervention mechanism with
      circumferentially pneumatic-driven clamping function.
AB  - BACKGROUND: Robot-assisted manipulation is promising for solving problems such as
      understaffing and the risk of infection in gastro-intestinal endoscopy. However,
      the commonly used friction rollers in few existing systems have a potential risk
      of deforming flexible endoscopes for non-uniform clamping. METHODS: This paper
      presents a robotic system for a standard flexible endoscope and focuses on a
      novel gastroscope intervention mechanism (GIM), which provides circumferentially
      uniform clamping with an airbag. The GIM works with a relay-on mechanism in a way
      similar to manual operation. The shear stiffness of airbag and the critical
      slipping force (CSF) were analysed to determine the parameters of the airbag. A
      fuzzy PID controller was employed to realize a fast response and high accuracy of
      pneumatic actuation. Experiments were performed to evaluate the accuracy,
      stiffness and CSF. In vitro and in vivo animal experiments were also carried out.
      RESULTS: The GIM realized an accuracy of 0.025 +/- 0.2 mm and -0.03 +/- 0.25
      degrees  for push-pull and rotation without delivery resistance. Under < 10 N
      delivery resistance, the error caused by the airbag stiffness was < 0.24 mm. A
      quadratic polynomial could be used to describe the relationship between the CSF
      and pneumatic pressure. CONCLUSIONS: The novel GIM could effectively deliver
      gastroscopes. The pneumatic-driven clamping method proposed could protect the
      gastroscope by circumferentially uniform clamping force and the CSF could be
      properly controlled to guarantee operating safety. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27028567
TI  - Defining your legacy in nursing.

PMID- 27028566
TI  - Functional characterization of CYP52G3 from Aspergillus oryzae and its
      application for bioconversion and synthesis of hydroxyl flavanone and steroids.
AB  - Aspergillus oryzae is a fungus widely used in traditional Japanese fermentation
      industries. Cytochrome P450 (CYP) proteins are ubiquitously distributed in nature
      and display a broad range of enzymatic activities. A novel CYP52 (CYP52G3) gene
      was found in A. oryzae. In this study, we report the functional characterization
      of CYP52G3. The recombinant protein was expressed heterologously in Escherichia
      coli, and its membrane fraction isolated. CYP52G3 showed activities for 7
      ethoxycoumarin and alpha-naphtoflavone. Furthermore, CYP52G3 hydroxylated
      flavanone at the 4' and 6 position and metabolized some hydroxyl-flavanones and
      steroids. Bioconversion experiments indicated that CYP52G3 could convert
      flavanone and testosterone in a synthetic medium. The conversion rates of
      flavanone and testosterone at 24 H were 50% and 70%, respectively. These results
      support that CYP52G3 could prove a useful enzyme for the efficient production of
      new compounds from flavonoids and steroids.

PMID- 27028569
TI  - Abstracts of the 20th Annual Meeting of French Society of Pharmacology and
      Therapeutics, 37th Pharmacovigilance Meeting, 17th APNET Seminar, 14th CHU CIC
      Meeting, 19-21 April 2016, Nancy, France.

PMID- 27028568
TI  - The promise of big data: Improving patient safety and nursing practice.

PMID- 27028570
TI  - Study of Insulin Requirement Modeling in Hospitalized Elderly Patients with Type
      2 Diabetes at a Late Stage of Stepwise Escalation Therapy.
AB  - BACKGROUND: This study explored the relationships between exogenous insulin
      requirements and endogenous variables in elderly patients with type 2 diabetes
      (T2D). SUBJECTS AND METHODS: Patients with T2D 65 years of age or older were
      enrolled for a short hospitalization period in order to start or change their
      basal-bolus therapy. The following data were collected: age, sex, diabetes
      duration, body mass index, glycosylated hemoglobin, estimated glomerular
      filtration rate (eGFR), and triglyceride (TG) levels. RESULTS: Data from 71
      elderly T2D patients (31 men/40 women; 75.7 +/- 6 years of age) were analyzed by
      data mining techniques. The total daily dose of insulin (TDI) ranged from 0.24
      U/kg to 2.5 U/kg (ratio >1:10). Three clusters of patients were identified:
      Cluster 1 (n = 22) consisted of older patients (age, 82.05 +/- 3.6 years) (P <
      0.0001) with a TDI of 0.59 +/- 0.21 U/kg/day and lower TG level (1.1 +/- 0.4
      mmol/L) (P < 0.0001). Cluster 2 (n = 22) consisted of patients with a TDI of 0.71
      +/- 0.24 U/kg/day with a higher eGFR (75.3 +/- 18.8 mL/min) (P < 0.001) and a
      shorter duration of diabetes (13.6 +/- 6.4 years) (P < 0.001). Cluster 3 (n = 27)
      consisted of patients with a larger proportion of macroangiopathic complications
      (P < 0.05), having a TDI of 1.31 +/- 0.54 U/kg/day, higher TG level (2.2 +/- 0.7
      mmol/L) (P < 0.001), and lower eGFR (46.3 +/- 16 mL/min). The average basal-bolus
      ratio was 43%/57% with a maximum bolus requirement due to carbohydrate intake at
      breakfast. CONCLUSIONS: Insulin requirements in elderly T2D patients vary widely.
      Age, TG level, and eGFR appeared to be the most predictive factors of TDI.
      Because of the small sample size, further studies would be required to
      extrapolate these results.

PMID- 27028571
TI  - Magnetic surfactants as molecular based-magnets with spin glass-like properties.
AB  - This paper reports the use of muon spin relaxation spectroscopy to study how the
      aggregation behavior of magnetic surfactants containing lanthanide counterions
      may be exploited to create spin glass-like materials. Surfactants provide a
      unique approach to building in randomness, frustration and competing interactions
      into magnetic materials without requiring a lattice of ordered magnetic species
      or intervening ligands and elements. We demonstrate that this magnetic behavior
      may also be manipulated via formation of micelles rather than simple dilution, as
      well as via design of surfactant molecular architecture. This somewhat unexpected
      result indicates the potential of using novel magnetic surfactants for the
      generation and tuning of molecular magnets. 

PMID- 27028572
TI  - Postoperative AMH reduction is not associated with reduced fecundity two years
      following ovarian cyst surgery.
AB  - In a prospective study, we investigated the impact of anti-Mullerian hormone
      (AMH) changes following ovarian cyst surgery on the probability to achieve
      pregnancy and live birth. Women of reproductive age (n = 60) were included before
      surgery for benign ovarian cysts. Serum AMH concentrations were determined pre-
      and postoperative at 6 and 24 months. Information regarding pregnancy wish and
      attempts to conceive were obtained by a questionnaire. At the time of inclusion,
      45/60 women reported desire of children. At six months, the levels of AMH
      decreased significantly in the whole group and further reduction was observed at
      two years (from 2.7 MUg/L to 2.0 MUg/L to 1.1 MUg/L, respectively, p<  0.008),
      with a percentage reduction of 42.9%. At two-year follow-up, 36 women reported to
      have attempted to conceive and 18 achieved pregnancy (50%), with a live birth
      rate of 33%. The percentage change in AMH at two years did not differ
      significantly between the women who conceived versus those who did not (p =
      0.117). Data reported herein demonstrate that the AMH reduction following ovarian
      cyst surgery is maintained two years after surgery; however, the postoperative
      AMH decrease that follows ovarian cyst surgery might not reduce the chances to
      achieve pregnancy.

PMID- 27028574
TI  - Molecular genetics of essential hypertension.
AB  - Hypertension is a major public health problem in the developing as well as in
      developed countries due to its high prevalence and its association with coronary
      heart disease, renal disease, stroke, peripheral vascular disease, and related
      disorders. Essential hypertension (EH) is the most common diagnosis in this
      disease, suggesting that a monocausal etiology has not been identified. However,
      a number of risk factors associated with EH have also been identified such as
      age, sex, demographic, environmental, genetic, and vascular factors. Recent
      advances in molecular biological research had achieved clarifying the molecular
      basis of Mendelian hypertensive disorders. Molecular genetic studies have now
      identified mutations in several genes that cause Mendelian forms of hypertension
      in humans. However, none of the single genetic variants has emerged from linkage
      or association analyses as consistently related to the blood pressure level in
      every sample and in all populations. Besides, a number of polymorphisms in
      candidate genes have been associated with differences in blood pressure. The most
      prominent candidate has been the polymorphisms in the renin-angiotensin
      aldosterone system. In total, EH is likely to be a polygenic disorder that
      results from inheritance of a number of susceptibility genes and involves
      multiple environmental determinants. These determinants complicate the study of
      blood pressure variations in the general population. The complex nature of the
      hypertension phenotype makes large-scale studies indispensable, when screening of
      familial and genetic factors was intended. In this review, recent genetic studies
      exploring the molecular basis of EH, including different molecular pathways, are
      highlighted. 

PMID- 27028575
TI  - Postmenopausal hormone therapy in the Brazilian Longitudinal Study of Adult
      Health (ELSA-Brasil): who still uses it?
AB  - PURPOSE: We aim to investigate the patterns of hormone therapy (HT) use and
      associated factors in women participating in the Brazilian Longitudinal Study of
      Adult Health. METHODS: This study included 3281 naturally menopausal women of 40
      to 74 years of age at enrollment to the Brazilian Longitudinal Study of Adult
      Health study, who answered questions regarding their use and discontinuation of
      HT. Prevalence rates of current and previous HT use were calculated, and a
      multinomial logistic regression model was constructed to simultaneously analyze
      the associated factors. RESULTS: The prevalence of HT use increased from 1995
      onwards, peaking at 55.7% in 1997. A sharp decline occurred in the decade
      beginning in 2000, reaching 11.1% at the study baseline interview (2008-2010).
      Current use was associated with being >=60 years of age (Relative Risk Ratio
      (RRR): 1.81; 95%CI: 1.10-2.96), divorced (RRR: 1.72; 95%CI: 1.14-2.60), or
      married (RRR: 2.09; 95%CI: 1.41-3.10); having a university education (RRR: 1.66;
      95%CI: 1.14-2.40) or postgraduate degree (RRR: 2.45; 95%CI: 1.80-3.35); and
      having private health insurance (RRR: 2.86; 95%CI: 2.00-4.09). Body mass index
      >=30 kg/m(2) was inversely associated with HT use (RRR: 0.37; 95%CI: 0.26-0.53)
      as was the presence of at least one contraindication to HT use (RRR: 0.63; 95%CI:
      0.44-0.89). Of the current users >=60 years of age, 79.1% had been using HT for
      at least 5 years, and 73.6% had been menopausal for at least 10 years.
      CONCLUSION: Although the use of HT has declined in Brazil, the women who continue
      using it are largely exceeding evidence-based limits of age, time since
      menopause, and time of use. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27028576
TI  - A Comparison of Inverse-Wishart Prior Specifications for Covariance Matrices in
      Multilevel Autoregressive Models.
AB  - Multilevel autoregressive models are especially suited for modeling between
      person differences in within-person processes. Fitting these models with Bayesian
      techniques requires the specification of prior distributions for all parameters.
      Often it is desirable to specify prior distributions that have negligible effects
      on the resulting parameter estimates. However, the conjugate prior distribution
      for covariance matrices-the Inverse-Wishart distribution-tends to be informative
      when variances are close to zero. This is problematic for multilevel
      autoregressive models, because autoregressive parameters are usually small for
      each individual, so that the variance of these parameters will be small. We
      performed a simulation study to compare the performance of three Inverse-Wishart
      prior specifications suggested in the literature, when one or more variances for
      the random effects in the multilevel autoregressive model are small. Our results
      show that the prior specification that uses plug-in ML estimates of the variances
      performs best. We advise to always include a sensitivity analysis for the prior
      specification for covariance matrices of random parameters, especially in
      autoregressive models, and to include a data-based prior specification in this
      analysis. We illustrate such an analysis by means of an empirical application on
      repeated measures data on worrying and positive affect. 

PMID- 27028577
TI  - Lung cancer screening - practical challenges of confining participation to those
      who might benefit.

PMID- 27028579
TI  - Cellular plasticity in the adult liver and stomach.
AB  - Adult tissues maintain function and architecture through robust homeostatic
      mechanisms mediated by self-renewing cells capable of generating all resident
      cell types. However, severe injury can challenge the regeneration potential of
      such a stem/progenitor compartment. Indeed, upon injury adult tissues can exhibit
      massive cellular plasticity in order to achieve proper tissue regeneration,
      circumventing an impaired stem/progenitor compartment. Several examples of such
      plasticity have been reported in both rapidly and slowly self-renewing organs and
      follow conserved mechanisms. Upon loss of the cellular compartment responsible
      for maintaining homeostasis, quiescent or slowly proliferating stem/progenitor
      cells can acquire high proliferation potential and turn into active stem cells,
      or, alternatively, mature cells can de-differentiate into stem-like cells or re
      enter the cell cycle to compensate for the tissue loss. This extensive cellular
      plasticity acts as a key mechanism to respond to multiple stimuli in a context
      dependent manner, enabling tissue regeneration in a robust fashion. In this
      review cellular plasticity in the adult liver and stomach will be examined,
      highlighting the diverse cell populations capable of repairing the damaged
      tissue.

PMID- 27028580
TI  - Structure of smAKAP and its regulation by PKA-mediated phosphorylation.
AB  - The A-kinase anchoring protein (AKAP) smAKAP has three extraordinary features; it
      is very small, it is anchored directly to membranes by acyl motifs, and it
      interacts almost exclusively with the type I regulatory subunits (RI) of cAMP
      dependent kinase (PKA). Here, we determined the crystal structure of smAKAP's A
      kinase binding domain (smAKAP-AKB) in complex with the dimerization/docking (D/D)
      domain of RIalpha which reveals an extended hydrophobic interface with unique
      interaction pockets that drive smAKAP's high specificity for RI subunits. We also
      identify a conserved PKA phosphorylation site at Ser66 in the AKB domain which we
      predict would cause steric clashes and disrupt binding. This correlates with in
      vivo colocalization and fluorescence polarization studies, where Ser66 AKB
      phosphorylation ablates RI binding. Hydrogen/deuterium exchange studies confirm
      that the AKB helix is accessible and dynamic. Furthermore, full-length smAKAP as
      well as the unbound AKB is predicted to contain a break at the phosphorylation
      site, and circular dichroism measurements confirm that the AKB domain loses its
      helicity following phosphorylation. As the active site of PKA's catalytic subunit
      does not accommodate alpha-helices, we predict that the inherent flexibility of
      the AKB domain enables its phosphorylation by PKA. This represents a novel
      mechanism, whereby activation of anchored PKA can terminate its binding to smAKAP
      affecting the regulation of localized cAMP signaling events. DATABASE: Structural
      data are available in the PDB under accession number 5HVZ.

PMID- 27028578
TI  - New advances in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic
      patients and the third cause of cancer related deaths. Most HCC are associated
      with well known underlying risk factors, in fact, HCC arise in cirrhotic patients
      in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse.
      The worldwide prevention strategies are conducted to avoid the infection of new
      subjects and to minimize the risk of liver disease progression in infected
      patients. HCC is a condition which lends itself to surveillance as at-risk
      individuals can readily be identified. The American and European guidelines
      recommended implementation of surveillance programs with ultrasound every six
      months in patient at-risk for developing HCC. The diagnosis of HCC can be based
      on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately
      staging patients is essential to oncology practice. The ideal tumour staging
      system in HCC needs to account for both tumour characteristics and liver
      function. Treatment allocation is based on several factors: Liver function, size
      and number of tumours, macrovascular invasion or extrahepatic spread. The
      recommendations in terms of selection for different treatment strategies must be
      based on evidence-based data. Resection, liver transplant and interventional
      radiology treatment are mainstays of HCC therapy and achieve the best outcomes in
      well-selected candidates. Chemoembolization is the most widely used treatment for
      unresectable HCC or progression after curative treatment. Finally, in patients
      with advanced HCC with preserved liver function, sorafenib is the only approved
      systemic drug that has demonstrated a survival benefit and is the standard of
      care in this group of patients. 

PMID- 27028581
TI  - Course of residual symptoms according to the duration of euthymia in remitted
      bipolar patients.
AB  - OBJECTIVE: Although many studies showed the negative impact of residual symptoms
      on the course of bipolar disorder (BD), there is a need to examine potential
      differences in residual symptoms according to the duration of euthymia in
      remitted BD patients. METHOD: This was a large cross-sectional study of 525
      euthymic BD out-patients. A multivariate analysis of covariance was conducted to
      compare depressive and manic residual symptoms, sleep disturbances and cognitive
      complaints among three patient groups on the basis of duration of euthymia (A. 6
      months to <1 year; B. 1 year to <3 years; C. 3 years to <=5 years). RESULTS: A
      significant difference between the three groups was found in residual symptoms
      [Pillai's Trace: F(8942) = 4.659, P < 0.001]. Tukey post hoc analysis indicated
      that patients from Group C presented lower residual depressive symptoms, higher
      sleep quality and better perceived cognitive performance compared with Group A.
      Group B also presented better sleep and cognitive outcomes than Group A. In
      addition, Group C showed the lowest incidence of functional impairment.
      CONCLUSION: This study suggests that the intensity of residual symptoms and
      functional impairment in remitted BD patients is negatively related to the
      duration of euthymia.

PMID- 27028582
TI  - Improving the Safety and Effectiveness of Medical Device Therapy in Women.
AB  - When not enough women are included in many clinical trials, an information gap on
      medical device safety and effectiveness exists, which can make it difficult to
      detect sex-specific results. In this article we discuss potential reasons for the
      underrepresentation of women and the regulatory research conducted by the U.S.
      Food and Drug Administration (FDA) used in supporting regulatory decisions. We
      demonstrate that important differences in cardiovascular device performance
      between women and men exist. Furthermore, concrete steps are outlined on the
      possible ways these sex-specific results can be detected and how a recent FDA
      Action Plan and Guidance Document aim at encouraging female participation in
      clinical trials and the appropriate analysis thereof.

PMID- 27028583
TI  - Differences in the paranasal sinuses between germ-free and pathogen-free mice.
AB  - BACKGROUND: The role of bacteria in the etiology of chronic rhinosinusitis (CRS)
      is not fully understood. Commensal bacteria may have a significant impact on the
      development of normal paranasal sinus anatomy and mucosal immunity, as they do in
      the gut. Studying the paranasal sinuses of germ-free (GF) mice may provide some
      insight into the effect of commensal bacteria on sinus structure and mucosal
      function. METHODS: The paranasal sinuses of 5 GF mice were compared to 5 pathogen
      free normal mice. Mice heads underwent computed tomography and images were
      compared for pneumatization and geometry of the sinuses. Histologically, slides
      were examined by light microscopy and compared for mucosal thickness, epithelial
      thickness, cilia, collagen, goblet cells, and nasal-associated lymphatic tissue
      (NALT). RESULTS: No radiological differences were seen between groups. Overall,
      GF mice were found to have thinner mucosa (Delta 15.2 +/- 5.2 MUm, p = 0.004),
      thinner epithelium (Delta 5.5 +/- 2.6 MUm, p = 0.037), more collagen (Delta 5.8%
      +/- 1.6%, p < 0.001), fewer goblet cells (Delta 29.3 +/- 5.4, p < 0.001), and
      less NALT (Delta 14,900 +/- 6700 MUm(2) , p = 0.04). Subanalysis by region
      revealed significant differences for GF mice in the middle (thinner mucosa,
      thinner epithelium, fewer cilia, and more collagen) and posterior (fewer goblet
      cells) sinus sections. CONCLUSION: The results of this study demonstrate that
      commensal microbiota significantly contribute to the structure and function of
      murine paranasal sinuses. Therefore, changes in commensal microbiota associated
      with CRS may alter the normal microbe host dialogue in humans and be implicated
      in the pathogenesis of CRS.

PMID- 27028584
TI  - Can Sex Partner Therapy Treat Sexual Distress and Dysfunction in Transgender
      Patients After Gender Confirmation Surgery?
AB  - Sex surrogacy, or sex partner therapy (SPT), is a form of therapy that aims to
      increase patients' comfort and confidence in sexual activity through a
      supportive, often sexually (though not necessarily) intimate connection with a
      trained surrogate partner/sex therapist. The therapy has been used to treat
      various disabilities, sexual dysfunctions, and anxieties related to sexual
      activity. Recently, there has been discussion about using SPT as a treatment for
      sexual distress and dysfunction in transgender patients who have undergone gender
      confirmation surgery (GCS). The use of SPT in this patient population has not
      been studied. The purpose of this letter to the editor is to call attention to
      and encourage discussion about the potential benefits and risks of using SPT as a
      treatment modality for sexual distress and dysfunction in post-GCS patients. 

PMID- 27028587
TI  - Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement
      study among genitourinary pathologists.
AB  - AIMS: To assess the interobserver reproducibility of individual Gleason grade 4
      growth patterns. METHODS AND RESULTS: Twenty-three genitourinary pathologists
      participated in the evaluation of 60 selected high-magnification photographs. The
      selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per
      growth pattern), and 10 of Gleason grade 5. Participants were asked to select a
      single predominant Gleason grade per case (3, 4, or 5), and to indicate the
      predominant Gleason grade 4 growth pattern, if present. 'Consensus' was defined
      as at least 80% agreement, and 'favoured' as 60-80% agreement. Consensus on
      Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to
      grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13,
      54%) patterns were involved in the disagreement. Among the 20 cases where at
      least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20)
      reached consensus. Consensus for fused, cribriform and glomeruloid glands was
      reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus
      Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these
      were characterized by large epithelial proliferations with delicate intervening
      fibrovascular cores, which were alternatively given the designation fused or
      cribriform growth pattern ('complex fused'). CONCLUSIONS: Consensus on Gleason
      grade 4 growth pattern was predominantly reached on cribriform and glomeruloid
      patterns, but rarely on ill-formed and fused glands. The complex fused glands
      seem to constitute a borderline pattern of unknown prognostic significance on
      which a consensus could not be reached.

PMID- 27028588
TI  - The first international workshop on the epigenetics of osteoarthritis.
AB  - Osteoarthritis (OA) is a major clinical problem across the world, in part due to
      the lack of disease-modifying drugs resulting, to a significant degree, from our
      incomplete understanding of the underlying molecular mechanisms of the disease.
      Emerging evidence points to a role of epigenetics in the pathogenesis of OA, but
      research in this area is still in its early stages. In order to summarize current
      knowledge and to facilitate the potential coordination of future research
      activities, the first international workshop on the epigenetics of OA was held in
      Amsterdam in October 2015. Recent findings on DNA methylation and
      hydroxymethylation, histone modifications, noncoding RNAs, and other epigenetic
      mechanisms were presented and discussed. The workshop demonstrated the advantage
      of bringing together those working in this nascent field and highlights from the
      event are summarized in this report in the form of summaries from invited
      speakers and organizers.

PMID- 27028589
TI  - Gender Differences in Cognitive Test Performance in Adults With Heart Failure.
AB  - BACKGROUND: Cognitive deficits are found in up to 73% of persons with heart
      failure (HF) and are associated with increased mortality and other poor clinical
      outcomes. It is known that women have better memory test performance than men do
      in healthy samples, but gender differences in cognitive performance in the
      context of HF are not well understood and may have important clinical
      implications. OBJECTIVE: The objective of this study was to examine possible
      gender differences in cognitive function in a sample of individuals with HF
      (98.9% New York Heart Association class II and III). METHODS: A total of 183
      adults with HF (116 men and 67 women) completed a neuropsychological test battery
      as part of a larger project. Measures were chosen to assess functioning in
      attention/executive function and memory. RESULTS: After controlling for
      demographic and medical factors, multivariate analysis of covariance revealed
      that men and women differed on memory test performance (lambda = 0.90, F4, 169 =
      4.76, P = .001). Post hoc comparisons revealed that women performed better on
      California Verbal Learning Test Learning, Short Recall, and Delayed Recall. No
      differences emerged on tests of attention/executive function (lambda = 0.97, F5,
      168 = 0.96, P = .44). CONCLUSIONS: In this sample of persons with HF, men
      exhibited poorer performance on memory measures than women did. Future studies
      are needed to determine the underlying mechanisms for this pattern and its
      possible influence on daily function.

PMID- 27028590
TI  - Inpatient Unit Heart Failure Discharge Volume Predicts All-cause 30-Day Hospital
      Readmission.
AB  - BACKGROUND: All-cause 30-day hospital readmission is a heart failure (HF) quality
      of care metric. Readmission costs the healthcare system $30.7 million annually.
      Specific structure, process, or patient factors that predispose patients to
      readmission are unclear. OBJECTIVE: The aim of this study is to determine whether
      the addition of unit-level structural factors (attending medical service, patient
      to-nurse ratio, and unit HF volume) predicts readmission beyond patient factors.
      METHODS: A retrospective chart review of 425 patients who resided in Maryland and
      were discharged home in 2011 with the primary diagnosis of HF from a large, urban
      academic center was conducted. RESULTS: The patients were predominately (66.6%)
      black/African American, with mean (SD) age of 62.2 (14.8) years. Men represented
      48.2% of the sample; 32% had nonischemic HF, 31.3% had preserved ejection
      fractions, 25.4% had implantable cardioverter defibrillators, and 15.3% had
      permanent pacemakers. Average length of stay was 6.0 days. All-cause 30-day
      hospital readmission rate was 20.2%. Inpatient unit HF discharge volume
      significantly predicted readmission after controlling for patient factors.
      CONCLUSIONS: The study found that discharge from inpatient units with higher HF
      discharge volume was associated with increased risk of readmission. The findings
      suggest that in caring for patients with severe HF, inpatient unit HF discharge
      volume may negatively impact care processes, increasing the odds of hospital
      readmission. It is unclear what specific care processes are responsible. The
      discharge period is a vulnerable point in care transition that warrants further
      investigation.

PMID- 27028591
TI  - Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction:
      Evidence Meets Practice, Part II.
AB  - Pharmacologic treatment for systolic heart failure, otherwise known as heart
      failure with reduced ejection fraction, has been established through clinical
      trials and is formulated into guidelines to standardize the diagnosis and
      treatment. Since the introduction of angiotensin-converting enzyme inhibitors and
      vasodilators in the 1980s, many guideline-recommended therapies have emerged over
      the past 20 years targeting specific neurohormones, aldosterone, and
      catecholamines to treat heart failure. Part 2 of this series will describe beta
      blockers, digoxin, and aldosterone antagonists in the context of the mechanism of
      action in heart failure, investigational trials that showed beneficial effects,
      and the practical applications for clinical use.

PMID- 27028592
TI  - Hypoxia Modulates the Swelling-Activated Cl Current in Human Glioblastoma Cells:
      Role in Volume Regulation and Cell Survival.
AB  - The malignancy of glioblastoma multiforme (GBM), the most common human brain
      tumor, correlates with the presence of hypoxic areas, but the underlying
      mechanisms are unclear. GBM cells express abundant Cl channels whose activity
      supports cell volume and membrane potential changes, ultimately leading to cell
      proliferation, migration, and escaping death. In non-tumor tissues Cl channels
      are modulated by hypoxia, which prompted us to verify whether hypoxia would also
      modulate Cl channels in GBM cells. Our results show that in GBM cell lines, acute
      application of a hypoxic solution activates a Cl current displaying the
      biophysical and pharmacological features of the swelling-activated Cl current
      (ICl,swell ). We also found that acute hypoxia increased the cell volume by about
      20%, and a 30% hypertonic solution partially inhibited the hypoxia-activated Cl
      current, suggesting that cell swelling and the activation of the Cl current are
      sequential events. Notably, the hypoxia-induced cell swelling was followed by a
      regulatory volume decrease (RVD) mediated mainly by ICl,swell . Since, a hypoxia
      induced prolonged cell swelling is usually regarded as a death insult, we
      hypothesized that the hypoxia-activated Cl current could limit cell swelling and
      prevent necrotic death of GBM cells under hypoxic conditions. In accordance, we
      found that the ICl,swell inhibitor DCPIB hampered the RVD process, and more
      importantly it sensibly increased the hypoxia-induced necrotic death in these
      cells. Taken together, these results suggest that Cl channels are strongly
      involved in the survival of GBM cells in a hypoxic environment, and may thus
      represent a new therapeutic target for this malignant tumor. J. Cell. Physiol.
      232: 91-100, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028593
TI  - Cardiogenic shock complicating ST-elevation myocardial infarction: a very
      difficult clinical scenario.
AB  - Cardiogenic shock (CS) is a life threatening condition which complicates 5-15% of
      acute myocardial infarctions (AMI). Despite advances in medical and
      interventional techniques during the last decades, the incidence of CS has not
      changed much, and while survival rates have improved, CS remains the leading
      cause of AMI-related in-hospital death with mortality rates exceeding 50%. We
      provide an overview of the pathophysiology, etiology, clinical course, as well as
      medical and interventional management of patients with CS complicating AMI. 

PMID- 27028594
TI  - Capillary Electrophoresis-Nanoelectrospray Ionization-Selected Reaction
      Monitoring Mass Spectrometry via a True Sheathless Metal-Coated Emitter Interface
      for Robust and High-Sensitivity Sample Quantification.
AB  - A new sheathless transient capillary isotachophoresis (CITP)/capillary zone
      electrophoresis (CZE)-MS interface, based on a commercially available capillary
      with an integrated metal-coated ESI emitter, was developed in this study aiming
      at overcoming the reproducibility and ruggedness problems suffered to a certain
      degree by almost all the available CE-MS interfaces, and pushing the CE-MS
      technology suitable for routine sample analysis with high sensitivity. The new
      CITP/CZE-MS interface allows the electric contact between ESI voltage power
      supply and the CE separation liquid by using a conductive liquid that comes in
      contact with the metal-coated surface of the ESI emitter, making it a true
      sheathless CE-MS interface. Stable electrospray was established by avoiding the
      formation of gas bubbles from electrochemical reaction inside the CE capillary.
      Crucial operating parameters, such as sample loading volume, flow rate, and
      separation voltage, were systematically evaluated for their effects on both
      CITP/CZE separation efficiency and MS detection sensitivity. Around one hundred
      CITP/CZE-MS analyses can be easily achieved by using the new sheathless CITP/CZE
      interface without a noticeable loss of metal coating on the ESI emitter surface,
      or degrading of the ESI emitter performance. The reproducibility in analyte
      migration time and quantitative performance of the new interface was
      experimentally evaluated to demonstrate a LOQ below 5 attomole. 

PMID- 27028596
TI  - Carers of older adults' satisfaction with public mental health service
      clinicians: a qualitative study.
AB  - AIMS AND OBJECTIVES: The purpose of our paper was to explore primary caregivers'
      experience of the way public mental health nurses and other mental health
      clinicians responded to them as primary carers of older adults with mental
      illness. BACKGROUND: As populations age, the prevalence of mental illness in
      older adults will increase and the burden of care placed on family carers will
      intensify. While family carers are essential to the well-being and quality of
      life of older adults with mental illness, they frequently experience
      marginalisation from clinicians. DESIGN: An interpretative phenomenological
      analysis approach was used to inform data collection and analysis. METHOD:
      Individual, semistructured, audio-recorded qualitative interviews were conducted
      with a purposive sample of 30 primary carers. RESULTS: Two themes were abstracted
      from the data highlighting carers' contrasting satisfaction with, and delivery of
      culturally competent care by, clinicians. A third theme, strategies for enhancing
      carers' experience of care, incorporated carers' suggestions about ways to
      strengthen their experience of caring. CONCLUSION: Although some primary carers
      had favourable experiences with clinicians, most were dissatisfied and this, in
      turn, clouded their overall experience of caring. RELEVANCE TO CLINICAL PRACTICE:
      Our findings have implications for the provision of education, ongoing support
      for, and building the cultural competence of, clinicians about working with
      carers. They also highlight the need for a change in organisational and practice
      culture to encompass mutual respect and partnership with carers within the
      context of the providing person-centred care for carers and older adults with
      mental illness.

PMID- 27028595
TI  - Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That
      Directly Induces Lymphoma Cell Death via Large Pore Formation.
AB  - To develop a new therapeutic monoclonal Antibody (mAb) for Hodgkin lymphoma (HL),
      we immunized a BALB/c mouse with live HL cell lines, alternating between two HL
      cell lines. After hybridization, we screened the hybridoma clones by assessing
      direct cytotoxicity against a HL cell line not used for immunization. We
      developed this strategy for establishing mAb to reduce the risk of obtaining
      clonotypic mAb specific for single HL cell line. A newly established mouse anti
      human mAb (4713) triggered cytoskeleton-dependent, but complement- and caspase
      independent, cell death in HL cell lines, Burkitt lymphoma cell lines, and
      advanced adult T-cell leukemia cell lines. Intravenous injection of mAb 4713 in
      tumor-bearing SCID mice improved survival significantly. mAb 4713 was revealed to
      be a mouse anti-human pan-HLA class II mAb. Treatment with this mAb induced the
      formation of large pores on the surface of target lymphoma cells within 30 min.
      This finding suggests that the cell death process induced by this anti-pan HLA
      class II mAb may involve the same death signals stimulated by a cytolytic anti
      pan MHC class I mAb that also induces large pore formation. This multifaceted
      study supports the therapeutic potential of mAb 4713 for various forms of
      lymphoma. 

PMID- 27028598
TI  - Localization of the brachial plexus: Sonography versus anatomic landmarks.
AB  - PURPOSE: Interscalene brachial plexus blocks are performed for perioperative
      management of surgeries involving the shoulder. Historically, these procedures
      employed anatomic landmarks (AL) to determine the location of the brachial plexus
      as it passes between the anterior and middle scalene muscles in the neck. In this
      study, we compared the actual location of the brachial plexus as found with
      sonography (US) to the anticipated location using AL. METHODS: The location of
      the brachial plexus was evaluated using US and AL in 96 subjects. The distance
      between the two locations was measured. A multivariate analysis of variance was
      used to determine the significance of the difference and a 2 * 2 analysis of
      variance was used to compare differences in gender, height, and body mass index.
      RESULTS: The brachial plexus was located on average 1.8 cm inferior (p = 0.0001)
      and 0.2 cm lateral (p = 0.09) to the location determined with AL. A significant
      difference was also associated with gender (p = 0.03), but not with height or
      body mass index. CONCLUSIONS: US is a reliable method that accurately pinpoints
      the roots of the brachial plexus. The brachial plexus is often located inferior
      to the location anticipated using AL. (c) 2016 Wiley Periodicals, Inc. J Clin
      Ultrasound 44:411-415, 2016.

PMID- 27028599
TI  - Evolutionary Relationships and Biogeography of the Ant-Epiphytic Genus
      Squamellaria (Rubiaceae: Psychotrieae) and Their Taxonomic Implications.
AB  - Ecological research on ant/plant symbioses in Fiji, combined with molecular
      phylogenetics, has brought to light four new species of Squamellaria in the
      subtribe Hydnophytinae of the Rubiaceae tribe Psychotrieae and revealed that four
      other species, previously in Hydnophytum, need to be transferred to Squamellaria.
      The diagnoses of the new species are based on morphological and DNA traits, with
      further insights from microCT scanning of flowers and leaf delta(13)C ratios
      (associated with Crassulacean acid metabolism). Our field and phylogenetic work
      results in a new circumscription of the genus Squamellaria, which now contains 12
      species (to which we also provide a taxonomic key), not 3 as in the last
      revision. A clock-dated phylogeny and a model-testing biogeographic framework
      were used to infer the broader geographic history of rubiaceous ant plants in the
      Pacific, specifically the successive expansion of Squamellaria to Vanuatu, the
      Solomon Islands, and Fiji. The colonization of Vanuatu may have occurred from
      Fiji, when these islands were still in the same insular arc, while the
      colonization of the Solomon islands may have occurred after the separation of
      this island from the Fiji/Vanuatu arc. Some of these ant-housing epiphytes must
      have dispersed with their specialized ants, for instance attached to floating
      timber. Others acquired new ant symbionts on different islands.

PMID- 27028600
TI  - Stroke and Systemic Embolism After Successful Ablation of Typical Atrial Flutter.
AB  - BACKGROUND: Following successful cavotricuspid isthmus (CTI) ablation during
      typical atrial flutter (AFL), anticoagulation therapy is usually withdrawn.
      However, potential subsequent atrial fibrillation (AF) in these patients may
      increase embolic risk in the long term. Embolic rates in this setting have not
      been clearly established. Our aim was to determine the incidence of
      stroke/systemic embolism following radiofrequency ablation of AFL, particularly
      in those without a prior history of AF. HYPOTHESIS: After succesful AFL ablation,
      patients may suffer embolic complications in the long-term follow-up, mainly due
      to asymptomatic AF episodes. METHODS: We conducted a retrospective analysis of
      all patients who underwent CTI ablation due to AFL in our center between 2006 and
      2009. RESULTS: During the study period, 188 patients (mean age, 62.9 +/- 8.6
      years) underwent CTI ablation; 120 without prior AF were included in the study.
      At the end of the follow-up period (mean, 5.0 +/- 2.4 years), 56.7% of patients
      (68/120) remained in sinus rhythm, 7/120 experienced a recurrence of AFL, and
      45/120 (38%) developed AF. Ischemic stroke occurred in 11 patients and systemic
      embolism in 1. Of these patients, 5 had documented AF following AFL ablation. In
      the remaining 7 cases, previously undiagnosed AF was subsequently diagnosed at
      the time of stroke/embolism. CONCLUSIONS: Patients with AFL who undergo
      successful ablation are by no means free from embolic complications during long
      term follow-up, mainly due to a high rate of AF development. Given the
      difficulties in detecting AF and the uncertainty about the temporal relation of
      AF and stroke, oral anticoagulation may need to be continued in those patients
      with underlying stroke risk factors.

PMID- 27028601
TI  - Evaluation of zirconia-based posterior single crowns supported by zirconia
      implants: preliminary results of a prospective multicenter study.
AB  - OBJECTIVE: The aim of this uncontrolled prospective multicenter study was to
      determine the success and survival rate of posterior single crowns composed of
      zirconia frameworks hand-layered with a leucite-reinforced feldspathic ceramic
      supported by one-piece zirconia oral implants. MATERIAL AND METHODS: In two
      centers, sixty patients received 71 zirconia oral implants. To obtain a clear
      indication of posterior implant-supported single crowns (ISSCs), 14 patients (25
      implants) were excluded from the analysis (11 bridges, three anterior crowns).
      The remaining patients were provided with single implants in posterior regions.
      As one patient lost his implant and another refused further participation after
      final prosthesis insertion, 44 ISSCs/patients (19 females, 25 males) were
      available for evaluation. Of these patients, all were seen at prosthetic delivery
      and the 6- and 12-month follow-up appointments. Evaluations were performed using
      modified United States Public Health Service (USPHS) criteria. Restorations
      within Alpha and Bravo ratings were regarded as success. This included minor
      chippings, a slight roughness, slightly soundable restoration margins and minimal
      contour deficiencies. In case of more distinct defects that could, however, be
      repaired to a clinically acceptable level, restorations were regarded as
      surviving. Kaplan-Meier plots and log-rank tests were used for the
      success/survival analyses and the calculation of potential group differences
      (gender, jaw and center). RESULTS: After a mean observation period of 12.5 months
      (SD: 0.8 months), no ISSC had to be replaced, resulting in a Kaplan-Meier
      survival rate of 100%. The Kaplan-Meier success rate was 90.9% (one major
      chipping, one obvious roughness, one significant crevice and one pronounced over
      contouring). Minor chippings and occlusal roughness were frequent complications.
      No significantly different survival/success rates could be observed between the
      mentioned groups. CONCLUSION: The frequent incidence of minor chippings suggests
      a high technique sensitivity when providing zirconia implants with veneered
      zirconia-based crowns questioning its suitability for this indication.

PMID- 27028602
TI  - Gender and Impulsivity: Effects on Cue-Induced Alcohol Craving.
AB  - BACKGROUND: Numerous studies have demonstrated that trait impulsivity is linked
      to increased risk of developing alcohol-use disorders and other substance abuse.
      Impulsivity has also been shown in some studies to potentiate cue-induced drug
      cravings. Despite considerable evidence of gender differences in impulsivity and
      drug craving among individuals suffering from alcohol dependence and other drug
      use, little research has focused on these processes in healthy young men and
      women who may be at risk for developing alcohol-use disorders. The objective of
      this study was to investigate the relationship between impulsivity and cue
      induced craving, as well as possible gender differences in these effects among
      healthy young adults. METHODS: To that end, female (n = 22) and male (n = 14)
      social drinkers aged 18 to 25, recruited from an urban university campus,
      completed the Barratt Impulsiveness Scale and reported their alcohol cravings
      immediately before and after laboratory exposure to alcohol cues. RESULTS:
      Findings indicated that exposure to cues elicited increased alcohol cravings, but
      these effects did not differ by gender. Interestingly, a significant interaction
      of impulsivity and gender revealed that impulsivity predicted significantly
      higher cue-induced cravings in women, but not men. CONCLUSIONS: Findings
      underscore the importance of better understanding the interaction of situational
      factors (e.g., exposure to alcohol cues) and dispositional factors (e.g.,
      impulsivity) as potential contributors to drinking motivation. Future prospective
      research is needed to identify gender-specific risk factors for the development
      of problem drinking.

PMID- 27028603
TI  - Influence of Surface Modifications on the Spatiotemporal Microdistribution of
      Quantum Dots In Vivo.
AB  - For biomedical applications of nanoconstructs, it is a general prerequisite to
      efficiently reach the desired target site. In this regard, it is crucial to
      determine the spatiotemporal distribution of nanomaterials at the microscopic
      tissue level. Therefore, the effect of different surface modifications on the
      distribution of microinjected quantum dots (QDs) in mouse skeletal muscle tissue
      has been investigated. In vivo real-time fluorescence microscopy and particle
      tracking reveal that carboxyl QDs preferentially attach to components of the
      extracellular matrix (ECM), whereas QDs coated with polyethylene glycol (PEG)
      show little interaction with tissue constituents. Transmission electron
      microscopy elucidates that carboxyl QDs adhere to collagen fibers as well as
      basement membranes, a type of ECM located on the basolateral side of blood vessel
      walls. Moreover, carboxyl QDs have been found in endothelial junctions as well as
      in caveolae of endothelial cells, enabling them to translocate into the vessel
      lumen. The in vivo QD distribution is confirmed by in vitro experiments. The data
      suggest that ECM components act as a selective barrier depending on QD surface
      modification. For future biomedical applications, such as targeting of blood
      vessel walls, the findings of this study offer design criteria for nanoconstructs
      that meet the requirements of the respective application.

PMID- 27028605
TI  - Free sural artery perforator flap: An occasional gift in oral cavity
      reconstruction.
AB  - BACKGROUND: The medial sural artery perforator (MSAP) flap is becoming a popular
      strategy for reconstructing intraoral defects. We present a case in which no
      MSAPs were present, however, a perforator-based calf flap was successfully raised
      on the sural artery and used for tongue reconstruction. A corresponding anatomic
      study was undertaken to establish if this finding was reproducible. METHODS: A 58
      year-old woman underwent left hemiglossectomy for a squamous cell carcinoma of
      the tongue. Subsequently, 6 fresh frozen cadaveric limbs were dissected examining
      the blood supply of the posterior calf skin. RESULTS: The sural artery perforator
      (SAP) flap successfully reconstructed the defect. Our cadaveric study similarly
      demonstrated a septocutaneous SAP supplying the posterior calf skin in 1 of 6
      limbs. CONCLUSION: SAPs allow a favorable flap dissection, as opposed to the
      musculocutaneous course of MSAPs. Our findings provide further evidence of the
      versatility of the calf donor site. (c) 2016 Wiley Periodicals, Inc. Head Neck
      38: E2454-E2456, 2016.

PMID- 27028604
TI  - Infection site is predictive of outcome in acute lung injury associated with
      severe sepsis and septic shock.
AB  - BACKGROUND AND OBJECTIVE: Sepsis is a leading cause of acute lung injury (ALI);
      however, the characteristics and outcome of sepsis-associated ALI are poorly
      understood. We aimed to elucidate factors that predict patient outcome in sepsis
      associated ALI. METHODS: Secondary analysis of a multicenter, prospective,
      observational study was performed. RESULTS: Among 624 patients with severe sepsis
      and septic shock, 251 (40.2%) fulfilled the definition of American-European
      Consensus Conference definition of ALI. All-cause 28-day and in-hospital
      mortalities were 30.7% and 38.6%, respectively. More than 40% of ALI patients had
      neurological, cardiovascular and haematological dysfunctions or disseminated
      intravascular coagulation, all of which were associated with higher mortality. We
      report a significant correlation between infection site and mortality in patients
      with ALI, but not in those without ALI. The proportion of ALI was significantly
      higher in pulmonary sepsis; further, a complication of ALI was associated with
      higher mortality in sepsis from pulmonary and other sources, but not in abdominal
      sepsis. Among the other sepsis sites, urinary tract, central nervous system,
      catheter-related and undetermined foci of infection had worse outcomes when
      associated with ALI. None of the individual severe sepsis bundles, including
      fluid resuscitation and early antibiotic administration, correlated with
      mortality. Compliance with a set of sepsis management bundles was associated with
      better outcomes. CONCLUSION: In severe sepsis and septic shock, the proportion
      and effect on outcome was not uniform among infection sites. The infection site
      was predictive of outcome in patients with ALI but not in those without ALI.

PMID- 27028606
TI  - NMR Binding and Functional Assays for Detecting Inhibitors of S. aureus MnaA.
AB  - Nonessential enzymes in the staphylococcal wall teichoic acid (WTA) pathway serve
      as highly validated beta-lactam potentiation targets. MnaA (UDP-GlcNAc 2
      epimerase) plays an important role in an early step of WTA biosynthesis by
      providing an activated form of ManNAc. Identification of a selective MnaA
      inhibitor would provide a tool to interrogate the contribution of the MnaA enzyme
      in the WTA pathway as well as serve as an adjuvant to restore beta-lactam
      activity against methicillin-resistant Staphylococcus aureus (MRSA). However,
      development of an epimerase functional assay can be challenging since both MnaA
      substrate and product (UDP-GlcNAc/UDP-ManNAc) share an identical molecular
      weight. Herein, we developed a nuclear magnetic resonance (NMR) functional assay
      that can be combined with other NMR approaches to triage putative MnaA inhibitors
      from phenotypic cell-based screening campaigns. In addition, we determined that
      tunicamycin, a potent WTA pathway inhibitor, inhibits both S. aureus MnaA and a
      functionally redundant epimerase, Cap5P. 

PMID- 27028608
TI  - The Effect of Price and Socio-Economic Level on the Consumption of Sugar
      Sweetened Beverages (SSB): The Case of Ecuador.
AB  - The objective of this article is to estimate the own-price, cross-price and
      income elasticities of demand for SSB in Ecuador, as an indispensable step for
      predicting a reduction in the consumption of said beverages caused by the
      potential implementation of taxes in Ecuador. In addition, the own-price, cross
      price and income elasticities of sugar-free substitutes like mineral water and
      diet soft drinks and juices are also estimated. The data from the 2011-2012
      ENIGHUR, which contains detailed information on household consumption and
      socioeconomic variables, was used. The estimates are done using Deaton's Almost
      Ideal Demand System (AIDS) which accounts for differences in the quality of goods
      purchased. This demand system is estimated for different socio-economic groups,
      according to total household expenditure. The results reveal own-price
      elasticities for SSB between -1.17 and -1.33 depending on the socio-economic
      group, in line with the existing evidence for developed countries. Own-price
      elasticity for non-SSB is between -1 and -1.24. Income elasticities reveal that
      both SSB and non-SSB are normal goods with elasticities decreasing for higher
      socio-economic groups. These results show that the consumption of SSB is
      sensitive to price changes, meaning that the implementation of taxes on said
      beverages could be effective in reducing their consumption. The fact that non-SSB
      are also sensitive to price changes would indicate that subsidies could be
      implemented for the production of some of them. 

PMID- 27028607
TI  - Characterization of Early Cortical Neural Network Development in Multiwell
      Microelectrode Array Plates.
AB  - We examined neural network ontogeny using microelectrode array (MEA) recordings
      made in multiwell MEA (mwMEA) plates over the first 12 days in vitro (DIV). In
      primary cortical cultures, action potential spiking activity developed rapidly
      between DIV 5 and 12. Spiking was sporadic and unorganized at early DIV, and
      became progressively more organized with time, with bursting parameters,
      synchrony, and network bursting increasing between DIV 5 and 12. We selected 12
      features to describe network activity; principal components analysis using these
      features demonstrated segregation of data by age at both the well and plate
      levels. Using random forest classifiers and support vector machines, we
      demonstrated that four features (coefficient of variation [CV] of within-burst
      interspike interval, CV of interburst interval, network spike rate, and burst
      rate) could predict the age of each well recording with >65% accuracy. When
      restricting the classification to a binary decision, accuracy improved to as high
      as 95%. Further, we present a novel resampling approach to determine the number
      of wells needed for comparing different treatments. Overall, these results
      demonstrate that network development on mwMEA plates is similar to development in
      single-well MEAs. The increased throughput of mwMEAs will facilitate screening
      drugs, chemicals, or disease states for effects on neurodevelopment. 

PMID- 27028609
TI  - Non-linear feature extraction from HRV signal for mortality prediction of ICU
      cardiovascular patient.
AB  - Intensive care unit (ICU) patients are at risk of in-ICU morbidities and
      mortality, making specific systems for identifying at-risk patients a necessity
      for improving clinical care. This study presents a new method for predicting in
      hospital mortality using heart rate variability (HRV) collected from the times of
      a patient's ICU stay. In this paper, a HRV time series processing based method is
      proposed for mortality prediction of ICU cardiovascular patients. HRV signals
      were obtained measuring R-R time intervals. A novel method, named return map, is
      then developed that reveals useful information from the HRV time series. This
      study also proposed several features that can be extracted from the return map,
      including the angle between two vectors, the area of triangles formed by
      successive points, shortest distance to 45 degrees  line and their various
      combinations. Finally, a thresholding technique is proposed to extract the risk
      period and to predict mortality. The data used to evaluate the proposed algorithm
      obtained from 80 cardiovascular ICU patients, from the first 48 h of the first
      ICU stay of 40 males and 40 females. This study showed that the angle feature has
      on average a sensitivity of 87.5% (with 12 false alarms), the area feature has on
      average a sensitivity of 89.58% (with 10 false alarms), the shortest distance
      feature has on average a sensitivity of 85.42% (with 14 false alarms) and,
      finally, the combined feature has on average a sensitivity of 92.71% (with seven
      false alarms). The results showed that the last half an hour before the patient's
      death is very informative for diagnosing the patient's condition and to save
      his/her life. These results confirm that it is possible to predict mortality
      based on the features introduced in this paper, relying on the variations of the
      HRV dynamic characteristics. 

PMID- 27028612
TI  - Effects of Power Training on Mobility and Gait Biomechanics in Old Adults with
      Moderate Mobility Disability: Protocol and Design of the Potsdam Gait Study
      (POGS).
AB  - BACKGROUND: Walking speed decreases in old age. Even though old adults regularly
      participate in exercise interventions, we do not know how the intervention
      induced changes in physical abilities produce faster walking. The Potsdam Gait
      Study (POGS) will examine the effects of 10 weeks of power training and
      detraining on leg muscle power and, for the first time, on complete gait
      biomechanics, including joint kinematics, kinetics, and muscle activation in old
      adults with moderate mobility disability. METHODS/DESIGN: POGS is a randomized
      controlled trial with two arms, each crossed over, without blinding. Arm 1 starts
      with a 10-week control period to assess the reliability of the tests and is then
      crossed over to complete 25-30 training sessions over 10 weeks. Arm 2 completes
      25-30 exercise sessions over 10 weeks, followed by a 10-week follow-up
      (detraining) period. The exercise program is designed to improve lower extremity
      muscle power. Main outcome measures are: muscle power, gait speed, and gait
      biomechanics measured at baseline and after 10 weeks of training and 10 weeks of
      detraining. DISCUSSION: It is expected that power training will increase leg
      muscle power measured by the weight lifted and by dynamometry, and these
      increased abilities become expressed in joint powers measured during gait. Such
      favorably modified powers will underlie the increase in step length, leading
      ultimately to a faster walking speed. POGS will increase our basic understanding
      of the biomechanical mechanisms of how power training improves gait speed in old
      adults with moderate levels of mobility disabilities.

PMID- 27028615
TI  - The use of pre-operative halo traction to minimize risk for correction of severe
      scoliosis in a patient with Fontan circulation: a case report and review of
      literature.
AB  - PURPOSE: Patients with Fontan circulation have increased cardio-respiratory risk
      during major spinal surgery. We report a case of severe scoliosis with a Cobb
      angle of 123.3 degrees  in a 16-year-old boy with Fontan circulation treated with
      single stage posterior segmental pedicle screw instrumentation and fusion.
      METHODS: Case report. RESULTS: The use pre-operative halo-ring traction for a
      duration of 6 weeks in this case lead to improvement in cobb angle from 123.3
      degrees , kyphotic angle 87.1 degrees  to cobb angle of 78.0 degrees , kyphotic
      angle 57.2 degrees  (on bending and stress films). The operation was completed in
      150 min, blood loss 1050 ml (25 ml/kg), and cell salvage of 490 ml. He was
      immediately extubated post correction, but monitored in ICU for a day. Total
      length of stay was 8 days without any perioperative morbidity or allogeneic blood
      transfusion. Final post-operative radiograph showed a cobb angle of 44.2 degrees
      , kyphotic angle 22.8 degrees . Follow up at 27 months showed solid union with no
      significant loss of correction. CONCLUSION: From this case experience, pre
      operative halo traction is a useful surgical strategy in patients with Fontan
      circulation with severe kyposcoliosis to achieve adequate correction without
      additional osteotomies to minimize the risk of surgical correction.

PMID- 27028616
TI  - Tunable Push-Pull Interactions in 5-Nitrosopyrimidines.
AB  - The effect of push-pull interactions in a series of variously substituted 5
      nitrosopyrimidines on the strength of intramolecular hydrogen bonds, the height
      of rotational barriers around formally single bonds, UV-vis spectra and
      electrochemical behavior is explored. Intramolecular charge transfer (ICT) leads
      to a shift of electron density from electron-donating substituents, which is
      readily observable by NMR spectroscopy. The 5-nitroso group is able to form
      strong intramolecular hydrogen bonds with neighboring amino substituents. As a
      result, two rotamers with reversed orientation of the 5-nitroso group are
      observed for compounds with two different hydrogen-bond donors in neighboring
      positions. The barriers of interconversion between the two rotamers are strongly
      influenced by ICT, whereas the ratio of such rotamers depends primarily on the
      character of the hydrogen-bond donors. The ICT also significantly affects the
      position of UV-vis absorption maxima, which can be tuned in a broad range of 100
      nm by the selection of appropriate substituents. Finally, ICT influences
      oxidation potential of the 5-nitrosopyrimidines and the stability of the
      resulting nitroso radical cations, the structures of which are determined by EPR
      spectroscopy.

PMID- 27028618
TI  - Efficacy and Safety of Acupuncture for the Treatment of Functional Dyspepsia:
      Meta-Analysis.
AB  - OBJECTIVES: Functional dyspepsia (FD) is a common gastrointestinal disorder.
      Currently, no established optimal treatment is available. The aim of this study
      was to assess the efficacy of acupuncture in relieving symptoms and improving
      quality of life in patients with FD. METHODS: PubMed, MEDLINE, Web of Science,
      Sino-Med, China National Knowledge Infrastructure, VIP databases, and Google
      Scholar engine were searched from inception through April 2014 to identify
      randomized controlled trials of acupuncture therapy that reported on overall FD
      symptoms or FD-related quality of life as a primary outcome. The Cochrane
      Collaboration's risk of bias tool, RevMan 5.0, and Stata 12.0 software were used
      for meta-analysis. Data were pooled to calculate relative risk (RRs) and 95%
      confidence intervals (CIs) of substantial improvement after treatment for
      dichotomous data and mean differences (SMDs) and 95% CIs for continuous data
      using random-effects models. RESULTS: Twenty-four English- and Chinese-language
      articles describing randomized, placebo-controlled, clinical trials involving
      3097 patients were included. Acupuncture significantly improved FD symptoms in
      studies reporting outcomes using dichotomous (RR, 1.19; 95% CI, 1.12-1.27; p <
      0.001) and continuous (standardized MD [SMD], -0.78; 95% CI, -1.21 to -0.35; p =
      0.0004) variables. Pooled analyses showed that acupuncture improved FD-related
      (weighted MD [WMD], 5.97; 95% CI, 3.14-8.80; p = 0.0002) and health-related (WMD,
      6.83; 95% CI, 3.02-10.65; p = 0.004) quality of life, without serious adverse
      events. However, acupuncture failed to increase plasma motilin concentration
      (SMD, 0.67; 95% CI, -0.07 to 1.42; p = 0.08). CONCLUSIONS: Acupuncture appears to
      be efficacious in relieving FD symptoms and improving quality of life.

PMID- 27028617
TI  - Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the
      Secondary Prevention of Cardiovascular Disease.
AB  - Aspirin has been the cornerstone of therapy for the secondary prevention
      treatment of patients with cardiovascular disease since landmark trials were
      completed in the late 1970s and early 1980s that demonstrated the efficacy of
      aspirin for reducing the risk of ischemic events. Notwithstanding the consistent
      benefits demonstrated with aspirin for both acute and chronic cardiovascular
      disease, there are a number of toxicities associated with aspirin that have been
      showcased by recent long-term clinical trials that have included an aspirin
      monotherapy arm. As an inhibitor of cyclooxygenase (COX), aspirin impairs gastric
      mucosal protective mechanisms. Previous trials have shown that up to 15-20 % of
      patients developed gastrointestinal symptoms with aspirin monotherapy, and
      approximately 1 % of patients per year had a clinically significant bleeding
      event, including 1 in 1000 patients who suffered an intracranial or fatal bleed.
      These risks have been shown to be compounded for patients with acute coronary
      syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI) who
      are also treated with other antithrombotic agents during the acute
      care/procedural period, as well as for an extended time period afterwards. Given
      observations of substantial increases in bleeding rates from many prior long-term
      clinical trials that have evaluated aspirin together with other oral platelet
      inhibitors or oral anticoagulants, the focus of contemporary research has pivoted
      towards tailored antithrombotic regimens that attempt to either shorten the
      duration of exposure to aspirin or replace aspirin with an alternative
      antithrombotic agent. While these shifts are occurring, the safety profile of
      aspirin when used for the secondary prevention treatment of patients with
      established cardiovascular disease deserves further consideration.

PMID- 27028619
TI  - Gastrointestinal Microbiota and Colon Cancer.
AB  - The human gut microbiota plays a major role in the development and maintenance of
      good health. Many recent studies have attempted to define links between
      microbiota residents, their function and the development of colorectal cancer
      (CRC). Gut microbiota drive the development of inflammation within the colon and
      such inflammation is implicated in colonic neoplastic development. Although the
      precise mechanisms through which the microbiota is involved in cancer development
      remain elusive, the message is clear: the microbiota contributes to cancer risk
      by influencing a number of key host processes. It is also recognized that we have
      the ability to influence the role of the gut microbiota by considering our
      nutritional intake. We have always known that 'we are what we eat' but it is also
      true that 'they (our gut microbiota) are what we eat'. We therefore have a huge
      opportunity to positively influence our health through microbial manipulation.
      There is now a clear need to move past defining the constituents of the
      gastrointestinal microbiota and to focus more on understanding the functional
      capabilities of the resident microbial community and how this impacts on host
      health. One such emerging concept is the development of microbial biofilms which
      can form in the gut in conjunction with CRC tissue. By better understanding of
      the interaction between the host and its resident microbiota, in the context of
      health and cancer development, we will open new therapeutic and diagnostic
      opportunities for reducing the CRC global health burden. 

PMID- 27028620
TI  - Expression of prostaglandin receptors in Chlamydia trachomatis-infected recurrent
      spontaneous aborters.
AB  - A study was undertaken to quantify the expression of prostaglandin (PG) receptors
      and find the effect of gestational age on expression of PG receptor genes in
      Chlamydia trachomatis-infected recurrent spontaneous aborters (RSA). Endometrial
      curettage tissue (ECT) was collected from 130 RSA (Group I) and 100 age-matched
      controls (Group II) at the Department of Obstetrics and Gynecology, Safdarjung
      Hospital, New Delhi (India). PCR was performed for diagnosis of C. trachomatis
      cryptic plasmid; mRNA expression of PG receptor genes was assessed by real-time
      PCR (q-PCR), while serum progesterone/estrogen levels were determined by
      respective commercial kits. Data were evaluated statistically. A total of 15.4 %
      RSA (GroupI) were diagnosed as C. trachomatis-positive (200 bp), whereas controls
      were uninfected. q-PCR showed significant upregulation (P<0.0001) of PGE2 (EP-1,
      EP-2, EP-3, EP-4), PGF2alpha (FP) and PGI2 (IP) receptors in Group I versus Group
      II. The expression of PG receptors increased significantly with advanced
      gestational age (P<0.002); however, only contractile receptors, EP-1, EP-3 and
      FP, were positively correlated with gestational age in Group-I. In infected RSA,
      mean serum progesterone level was significantly low (P<0.0001) while serum
      oestrogen was high (P<0.0001). Overall, the data suggest that increased
      expression of PG receptors, particularly contractile gene receptors (EP-1, EP-3,
      FP), with advanced gestational age and altered steroid levels could be a possible
      risk factor for abortion in Chlamydia-infected RSA. 

PMID- 27028621
TI  - Effectiveness of Scotland's national naloxone programme.

PMID- 27028622
TI  - Nicotine-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells.
AB  - BACKGROUND: Nicotine is, to a large extent, responsible for smoking-mediated
      renal dysfunction. This study investigated nicotine's effects on renal tubular
      epithelial cell apoptosis in vitro and it explored the mechanisms underlying its
      effects. METHODS: Human proximal tubular epithelial (HK-2) cells were treated
      with nicotine. Cell viability was examined by using the WST-1 assay.
      Intracellular levels of reactive oxygen species (ROS) and the expression of
      mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB)
      proteins were determined. The messenger ribonucleic acid and the protein
      expression associated with the nicotine acetylcholine receptors (nAChRs) in HK-2
      cells was examined, and apoptosis was detected using flow cytometry, cell cycle
      analysis, and immunoblot analysis. RESULTS: The HK-2 cells were endowed with
      nAChRs. Nicotine treatment reduced cell viability dose dependently, increased ROS
      levels, and increased extracellular signal-regulated kinase (ERK), c-Jun N
      terminal kinase (JNK), and p38 MAPK expression. Nicotine increased NF-kappaB
      activation, which was attenuated by N-acetyl-L-cysteine, and ERK and JNK
      inhibitors, but was not affected by a p38 MAPK inhibitor. Nicotine increased the
      Bax/Bcl-2 ratio, which was attenuated by N-acetyl-L-cysteine, the NF-kappaB
      inhibitor, Bay 11-7082, and hexamethonium, a non-specific nAChR blocker. Flow
      cytometry revealed nicotine-induced G2/M phase arrest. While nicotine treatment
      increased the expression of phosphorylated cdc2 and histone H3, a marker of G2/M
      phase arrest, hexamethonium and Bay 11-7082 pretreatment reduced their
      expression. CONCLUSIONS: Nicotine caused apoptosis in HK-2 cells by inducing ROS
      generation that activated the NF-kappaB signaling pathway via the MAPK pathway
      and it arrested the cell cycle at the G2/M phase. Nicotine-induced apoptosis in
      HK-2 cells involves the nAChRs.

PMID- 27028623
TI  - RNAi-mediated resistance against Cotton leaf curl disease in elite Indian cotton
      (Gossypium hirsutum) cultivar Narasimha.
AB  - Cotton leaf curl disease (CLCuD) is caused by several distinct begomovirus
      species in association with disease-specific betasatellite essential for
      induction of disease symptoms. CLCuD is a serious threat for the cultivation of
      cotton (Gossypium sp.) and several species in the family Malvaceae. In this
      study, RNAi-based approach was applied to generate transgenic cotton (Gossypium
      hirsutum) plants resistant to Cotton leaf curl Rajasthan virus (CLCuRV). An
      intron hairpin (ihp) RNAi construct capable of expressing dsRNA homologous to the
      intergenic region (IR) of CLCuRV was designed and developed. Following
      Agrobacterium tumefaciens-mediated transformation of cotton (G. hirsutum cv.
      Narasimha) plants with the designed ihpRNAi construct, a total of 9 independent
      lines of transformed cotton were obtained. The presence of the potential stretch
      of IR in the transformed cotton was confirmed by PCR coupled with Southern
      hybridization. Upon inoculation with viruliferous whiteflies, the transgenic
      plants showed high degree of resistance. None of them displayed any CLCuD
      symptoms even after 90 days post inoculation. The transformed cotton plants
      showed the presence of siRNAs. The present study demonstrated that ihp dsRNA
      mediated resistance strategy of RNAi is an effective means to combat the CLCuD
      infection in cotton. 

PMID- 27028624
TI  - Nodular fasciitis on the face.

PMID- 27028625
TI  - Analysis of gene expression in mouse brain regions after exposure to 1.9 GHz
      radiofrequency fields.
AB  - PURPOSE: To assess 1.9 GHz radiofrequency (RF) field exposure on gene expression
      within a variety of discrete mouse brain regions using whole genome microarray
      analysis. MATERIALS AND METHODS: Adult male C57BL/6 mice were exposed to 1.9 GHz
      pulse-modulated or continuous-wave RF fields for 4 h/day for 5 consecutive days
      at whole body average (WBA) specific absorption rates of 0 (sham), ~0.2 W/kg and
      ~1.4 W/kg. Total RNA was isolated from the auditory cortex, amygdala, caudate,
      cerebellum, hippocampus, hypothalamus, and medial prefrontal cortex and
      differential gene expression was assessed using Illumina MouseWG-6 (v2) BeadChip
      arrays. Validation of potentially responding genes was conducted by RT-PCR.
      RESULTS: When analysis of gene expression was conducted within individual brain
      regions when controlling the false discovery rate (FDR), no differentially
      expressed genes were identified relative to the sham control. However, it must be
      noted that most fold changes among groups were observed to be less than 1.5-fold
      and this study had limited ability to detect such small changes. While some genes
      were differentially expressed without correction for multiple-comparisons
      testing, no consistent pattern of response was observed among different RF
      exposure levels or among different RF-modulations. CONCLUSIONS: The current study
      provides the most comprehensive analysis of potential gene expression changes in
      the rodent brain in response to RF field exposure conducted to date. Within the
      exposure conditions and limitations of this study, no convincing evidence of
      consistent changes in gene expression was found in response to 1.9 GHz RF field
      exposure.

PMID- 27028626
TI  - Hepatitis C treatment failure is associated with increased risk of hepatocellular
      carcinoma.
AB  - Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV)
      reduces risk of hepatocellular carcinoma (HCC), but there is little information
      regarding how treatment failure (TF) compares to lack of treatment. We evaluated
      the impact of treatment status on risk of HCC using data from the Chronic
      Hepatitis Cohort Study (CHeCS-an observational study based in four large US
      health systems, with up to 7 years of follow-up on patients). Multivariable
      analyses were used to adjust for bias in treatment selection, as well as other
      covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681
      (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582
      (43%) of these achieved sustained virological response (SVR). TF patients
      demonstrated almost twice the risk of HCC than untreated patients [adjusted
      hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50-2.53]; this risk
      persisted across all stages of fibrosis. Several sensitivity analyses validated
      these results. Although African Americans were at increased risk of treatment
      failure, they were at lower risk for HCC and all-cause mortality compared to
      White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48,
      CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause
      mortality (aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93
      for TF patients).

PMID- 27028628
TI  - Do marine phytoplankton follow Bergmann's rule sensu lato?
AB  - Global warming has revitalized interest in the relationship between body size and
      temperature, proposed by Bergmann's rule 150 years ago, one of the oldest
      manifestations of a 'biogeography of traits'. We review biogeographic evidence,
      results from clonal cultures and recent micro- and mesocosm experiments with
      naturally mixed phytoplankton communities regarding the response of phytoplankton
      body size to temperature, either as a single factor or in combination with other
      factors such as grazing, nutrient limitation, and ocean acidification. Where
      possible, we also focus on the comparison between intraspecific size shifts and
      size shifts resulting from changes in species composition. Taken together,
      biogeographic evidence, community-level experiments and single-species
      experiments indicate that phytoplankton average cell sizes tend to become smaller
      in warmer waters, although temperature is not necessarily the proximate
      environmental factor driving size shifts. Indirect effects via nutrient supply
      and grazing are important and often dominate. In a substantial proportion of
      field studies, resource availability is seen as the only factor of relevance.
      Interspecific size effects are greater than intraspecific effects. Direct
      temperature effects tend to be exacerbated by indirect ones, if warming leads to
      intensified nutrient limitation or copepod grazing while ocean acidification
      tends to counteract the temperature effect on cell size in non-calcifying
      phytoplankton. We discuss the implications of the temperature-related size trends
      in a global-warming context, based on known functional traits associated with
      phytoplankton size. These are a higher affinity for nutrients of smaller cells,
      highest maximal growth rates of moderately small phytoplankton (ca. 102  um3 ),
      size-related sensitivities for different types of grazers, and impacts on sinking
      rates. For a phytoplankton community increasingly dominated by smaller algae we
      predict that: (i) a higher proportion of primary production will be respired
      within the microbial food web; (ii) a smaller share of primary production will be
      channeled to the classic phytoplankton - crustacean zooplankton - fish food
      chain, thus leading to decreased ecological efficiency from a fish-production
      point of view; (iii) a smaller share of primary production will be exported
      through sedimentation, thus leading to decreased efficiency of the biological
      carbon pump.

PMID- 27028627
TI  - Assessing Concordance of Drug-Induced Transcriptional Response in Rodent Liver
      and Cultured Hepatocytes.
AB  - The effect of drugs, disease and other perturbations on mRNA levels are studied
      using gene expression microarrays or RNA-seq, with the goal of understanding
      molecular effects arising from the perturbation. Previous comparisons of
      reproducibility across laboratories have been limited in scale and focused on a
      single model. The use of model systems, such as cultured primary cells or cancer
      cell lines, assumes that mechanistic insights derived from the models would have
      been observed via in vivo studies. We examined the concordance of compound
      induced transcriptional changes using data from several sources: rat liver and
      rat primary hepatocytes (RPH) from Drug Matrix (DM) and open TG-GATEs (TG), human
      primary hepatocytes (HPH) from TG, and mouse liver/HepG2 results from the Gene
      Expression Omnibus (GEO) repository. Gene expression changes for treatments were
      normalized to controls and analyzed with three methods: 1) gene level for 9071
      high expression genes in rat liver, 2) gene set analysis (GSA) using canonical
      pathways and gene ontology sets, 3) weighted gene co-expression network analysis
      (WGCNA). Co-expression networks performed better than genes or GSA when comparing
      treatment effects within rat liver and rat vs. mouse liver. Genes and modules
      performed similarly at Connectivity Map-style analyses, where success at
      identifying similar treatments among a collection of reference profiles is the
      goal. Comparisons between rat liver and RPH, and those between RPH, HPH and HepG2
      cells reveal lower concordance for all methods. We observe that the baseline
      state of untreated cultured cells relative to untreated rat liver shows striking
      similarity with toxicant-exposed cells in vivo, indicating that gross systems
      level perturbation in the underlying networks in culture may contribute to the
      low concordance.

PMID- 27028629
TI  - Untangling a Structurally Resolved Protein Folding Intermediate.

PMID- 27028630
TI  - Allosteric Regulation of the M2 Protein from Influenza A by Cholesterol.

PMID- 27028631
TI  - A Primer on the Bayesian Approach to High-Density Single-Molecule Trajectories
      Analysis.
AB  - Tracking single molecules in living cells provides invaluable information on
      their environment and on the interactions that underlie their motion. New
      experimental techniques now permit the recording of large amounts of individual
      trajectories, enabling the implementation of advanced statistical tools for data
      analysis. In this primer, we present a Bayesian approach toward treating these
      data, and we discuss how it can be fruitfully employed to infer physical and
      biochemical parameters from single-molecule trajectories. 

PMID- 27028632
TI  - The Kinesin-1 Chemomechanical Cycle: Stepping Toward a Consensus.
AB  - Kinesin-1 serves as a model for understanding fundamentals of motor protein
      mechanochemistry and for interpreting functional diversity across the kinesin
      superfamily. Despite sustained work over the last three decades, disagreements
      remain regarding the events that trigger the two key transitions in the stepping
      cycle: detachment of the trailing head from the microtubule and binding of the
      tethered head to the next tubulin binding site. This review describes the
      conflicting views of these events and highlights recent work that sheds light on
      these long-standing controversies. It concludes by presenting a consensus kinesin
      1 chemomechanical that incorporates recent work, resolves discrepancies, and
      highlights key questions for future experimental work. It is hoped that this
      model provides a framework for understanding how diverse kinesins are tuned for
      their specific cellular roles. 

PMID- 27028633
TI  - A Method for Molecular Dynamics on Curved Surfaces.
AB  - Dynamics simulations of constrained particles can greatly aid in understanding
      the temporal and spatial evolution of biological processes such as lateral
      transport along membranes and self-assembly of viruses. Most theoretical efforts
      in the field of diffusive transport have focused on solving the diffusion
      equation on curved surfaces, for which it is not tractable to incorporate
      particle interactions even though these play a crucial role in crowded systems.
      We show here that it is possible to take such interactions into account by
      combining standard constraint algorithms with the classical velocity Verlet
      scheme to perform molecular dynamics simulations of particles constrained to an
      arbitrarily curved surface. Furthermore, unlike Brownian dynamics schemes in
      local coordinates, our method is based on Cartesian coordinates, allowing for the
      reuse of many other standard tools without modifications, including
      parallelization through domain decomposition. We show that by applying the
      schemes to the Langevin equation for various surfaces, we obtain confined
      Brownian motion, which has direct applications to many biological and physical
      problems. Finally we present two practical examples that highlight the
      applicability of the method: 1) the influence of crowding and shape on the
      lateral diffusion of proteins in curved membranes; and 2) the self-assembly of a
      coarse-grained virus capsid protein model. 

PMID- 27028634
TI  - Structural Fluctuations of the Chromatin Fiber within Topologically Associating
      Domains.
AB  - Experiments based on chromosome conformation capture have shown that mammalian
      genomes are partitioned into topologically associating domains (TADs), within
      which the chromatin fiber preferentially interacts. TADs may provide three
      dimensional scaffolds allowing genes to contact their appropriate distal
      regulatory DNA sequences (e.g., enhancers) and thus to be properly regulated.
      Understanding the cell-to-cell and temporal variability of the chromatin fiber
      within TADs, and what determines them, is thus of great importance to better
      understand transcriptional regulation. We recently described an equilibrium
      polymer model that can accurately predict cell-to-cell variation of chromosome
      conformation within single TADs, from chromosome conformation capture-based data.
      Here we further analyze the conformational and energetic properties of our model.
      We show that the chromatin fiber within TADs can easily fluctuate between several
      conformational states, which are hierarchically organized and are not separated
      by important free energy barriers, and that this is facilitated by the fact that
      the chromatin fiber within TADs is close to the onset of the coil-globule
      transition. We further show that in this dynamic state the properties of the
      chromatin fiber, and its contact probabilities in particular, are determined in a
      nontrivial manner not only by site-specific interactions between strongly
      interacting loci along the fiber, but also by nonlocal correlations between pairs
      of contacts. Finally, we use live-cell experiments to measure the dynamics of the
      chromatin fiber in mouse embryonic stem cells, in combination with dynamical
      simulations, and predict that conformational changes within one TAD are likely to
      occur on timescales that are much shorter than the duration of one cell cycle.
      This suggests that genes and their regulatory elements may come together and
      disassociate several times during a cell cycle. These results have important
      implications for transcriptional regulation as they support the concept of highly
      dynamic interactions driven by a complex interplay between site-specific
      interactions and the intrinsic biophysical properties of the chromatin fiber. 

PMID- 27028635
TI  - Influence of RNA Binding on the Structure and Dynamics of the Lassa Virus
      Nucleoprotein.
AB  - Lassa virus protects its viral genome through the formation of a
      ribonucleoprotein complex in which the nucleoprotein (NP) encapsidates the single
      stranded RNA genome. Crystal structures provide evidence that a conformational
      change must occur to allow for RNA binding. In this study, the mechanism by which
      NP binds to RNA and how the conformational changes in NP are achieved was
      investigated with molecular-dynamics simulations. NP was structurally
      characterized in an open configuration when bound to RNA and in a closed form in
      the absence of RNA. Our results show that when NP is bound to RNA, the protein is
      highly dynamic and the system undergoes spontaneous deviations away from the open
      state configuration. The equilibrium simulations are supported by free-energy
      calculations that quantify the influence of RNA on the free-energy surface, which
      governs NP dynamics. We predict that the globally stable states are qualitatively
      in agreement with the observed crystal structures, but that both open and closed
      conformations are thermally accessible in the presence of RNA. The free-energy
      calculations also provide a prediction of the location of the transition state
      for RNA binding and identify an intermediate metastable state that exhibits
      correlated motions that could promote RNA binding. 

PMID- 27028636
TI  - Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation.
AB  - DNA intercalators that have high affinity and slow kinetics are developed for
      potential DNA-targeted therapeutics. Although many natural intercalators contain
      multiple chiral subunits, only intercalators with a single chiral unit have been
      quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the
      next order of structural complexity relative to simple intercalators, and can
      provide significant insights into the stereoselectivity of DNA-ligand
      intercalation. We investigated DNA threading intercalation by binuclear ruthenium
      complex [MU-dppzip(phen)4Ru2](4+) (Piz). Four Piz stereoisomers are defined by
      the chirality of the intercalating subunit (Ru(phen)2dppz) and the distal subunit
      (Ru(phen)2ip), respectively, each of which can be either right-handed (Delta) or
      left-handed (Lambda). We used optical tweezers to measure single DNA molecule
      elongation due to threading intercalation, revealing force-dependent DNA
      intercalation rates and equilibrium dissociation constants. The force
      spectroscopy analysis provided the zero-force DNA binding affinity, the
      equilibrium DNA-ligand elongation Deltaxeq, and the dynamic DNA structural
      deformations during ligand association xon and dissociation xoff. We found that
      Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from
      a Kd of 27 +/- 3 nM for (Delta,Lambda)-Piz to a Kd of 622 +/- 55 nM for
      (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing
      Deltaxeq from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and xon from 0.25 +/- 0.01 to
      0.46 +/- 0.02 nm, but limited xoff changes. Notably, the affinity and threading
      kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5
      fold enhanced for left-handed distal subunits. These findings demonstrate
      sterically dispersed transition pathways and robust DNA structural recognition of
      chiral intercalators, which are critical for optimizing DNA binding affinity and
      kinetics.

PMID- 27028637
TI  - Insights into the Structural Dynamics of Nucleocytoplasmic Transport of tRNA by
      Exportin-t.
AB  - Exportin-t (Xpot) transports mature 5'- and 3'-end processed tRNA from the
      nucleus to the cytoplasm by associating with a small G-protein Ran (RAs-related
      nuclear protein), in the nucleus. The release of tRNA in cytoplasm involves
      RanGTP hydrolysis. Despite the availability of crystal structures of nuclear and
      cytosolic forms of Xpot, the molecular details regarding the sequential events
      leading to tRNA release and subsequent conformational changes occurring in Xpot
      remain unknown. We have performed a combination of classical all-atom and
      accelerated molecular dynamics simulations on a set of complexes involving Xpot
      to study a range of features including conformational flexibility of free and
      cargo-bound Xpot and functionally critical contacts between Xpot and its cargo.
      The systems investigated include free Xpot and its different complexes, bound
      either to Ran (GTP/GDP) or tRNA or both. This approach provided a statistically
      reliable estimate of structural dynamics of Xpot after cargo release. The
      mechanistic basis for Xpot opening after cargo release has been explained in
      terms of dynamic structural hinges, about which neighboring region could be
      displaced to facilitate the nuclear to cytosolic state transition. Post-RanGTP
      hydrolysis, a cascade of events including local conformational change in RanGTP
      and loss of critical contacts at Xpot/tRNA interface suggest factors responsible
      for eventual release of tRNA. The level of flexibility in different Xpot
      complexes varied depending on the arrangement of individual HEAT repeats. Current
      study provides one of the most comprehensive and robust analysis carried out on
      this protein using molecular dynamics schemes. 

PMID- 27028638
TI  - Single-Molecule Chemo-Mechanical Spectroscopy Provides Structural Identity of
      Folding Intermediates.
AB  - Single-molecule force spectroscopy has emerged as a powerful tool for studying
      the folding of biological macromolecules. Mechanical manipulation has revealed a
      wealth of mechanistic information on transient and intermediate states. To date,
      the majority of state assignment of intermediates has relied on empirical
      demarcation. However, performing such experiments in the presence of different
      osmolytes provides an alternative approach that reports on the structural
      properties of intermediates. Here, we analyze the folding and unfolding of T4
      lysozyme with optical tweezers under a chemo-mechanical perturbation by adding
      osmolytes. We find that two unrelated protective osmolytes, sorbitol and
      trimethylamine-n-oxide, function by marginally decelerating unfolding rates and
      specifically modulating early events in the folding process, stabilizing
      formation of an on-pathway intermediate. The chemo-mechanical perturbation
      provides access to two independent metrics of the relevant states during folding
      trajectories, the contour length, and the solvent-accessible surface area. We
      demonstrate that the dependence of the population of the intermediate in
      different osmolytes, in conjunction with its measured contour length, provides
      the ability to discriminate between potential structural models of intermediate
      states. Our study represents a general strategy that may be employed in the
      structural modeling of equilibrium intermediate states observed in single
      molecule experiments. 

PMID- 27028639
TI  - Cationic Peptides and Peptidomimetics Bind Glycosaminoglycans as Potential Sema3A
      Pathway Inhibitors.
AB  - Semaphorin3A (Sema3A) is a vertebrate-secreted protein that was initially
      characterized as a repulsive-guidance cue. Semaphorins have crucial roles in
      several diseases; therefore, the development of Sema3A inhibitors is of
      therapeutic interest. Sema3A interacts with glycosaminoglycans (GAGs), presumably
      through its C-terminal basic region. We used different biophysical techniques
      (i.e., NMR, surface plasmon resonance, isothermal titration calorimetry,
      fluorescence, and UV-visible spectroscopy) to characterize the binding of two
      Sema3A C-terminus-derived basic peptides (FS2 and NFS3) to heparin and
      chondroitin sulfate A. We found that these peptides bind to both GAGs with
      affinities in the low-micromolar range. On the other hand, a peptoid named SICHI
      (semaphorin-induced chemorepulsion inhibitor), which is positively charged at
      physiological pH, was first identified by our group as being able to block Sema3A
      chemorepulsion and growth-cone collapse in axons at the extracellular level. To
      elucidate the direct target for the reported SICHI inhibitory effect in the
      Sema3A signaling pathway, we looked first to the protein-protein interaction
      between secreted Sema3A and the Nrp1 receptor. However, our results show that
      SICHI does not bind directly to the Sema3A sema domain or to Nrp1 extracellular
      domains. We evaluated a new, to our knowledge, hypothesis, according to which
      SICHI binds to GAGs, thereby perturbing the Sema3A-GAG interaction. By using the
      above-mentioned techniques, we observed that SICHI binds to GAGs and competes
      with Sema3A C-terminus-derived basic peptides for binding to GAGs. These data
      support the ability of SICHI to block the biologically relevant interaction
      between Sema3A and GAGs, thus revealing SICHI as a new, to our knowledge, class
      of inhibitors that target the GAG-protein interaction. 

PMID- 27028640
TI  - Investigating DNA Radiation Damage Using X-Ray Absorption Spectroscopy.
AB  - The biological influence of radiation on living matter has been studied for
      years; however, several questions about the detailed mechanism of radiation
      damage formation remain largely unanswered. Among all biomolecules exposed to
      radiation, DNA plays an important role because any damage to its molecular
      structure can affect the whole cell and may lead to chromosomal rearrangements
      resulting in genomic instability or cell death. To identify and characterize
      damage induced in the DNA sugar-phosphate backbone, in this work we performed x
      ray absorption spectroscopy at the P K-edge on DNA irradiated with either UVA
      light or protons. By combining the experimental results with theoretical
      calculations, we were able to establish the types and relative ratio of lesions
      produced by both UVA and protons around the phosphorus atoms in DNA. 

PMID- 27028641
TI  - PIP Water Transport and Its pH Dependence Are Regulated by Tetramer
      Stoichiometry.
AB  - Many plasma membrane channels form oligomeric assemblies, and
      heterooligomerization has been described as a distinctive feature of some protein
      families. In the particular case of plant plasma membrane aquaporins (PIPs), PIP1
      and PIP2 monomers interact to form heterotetramers. However, the biological
      properties of the different heterotetrameric configurations formed by PIP1 and
      PIP2 subunits have not been addressed yet. Upon coexpression of tandem PIP2-PIP1
      dimers in Xenopus oocytes, we can address, for the first time to our knowledge,
      the functional properties of single heterotetrameric species having 2:2
      stoichiometry. We have also coexpressed PIP2-PIP1 dimers with PIP1 and PIP2
      monomers to experimentally investigate the localization and biological activity
      of each tetrameric assembly. Our results show that PIP2-PIP1 heterotetramers can
      assemble with 3:1, 1:3, or 2:2 stoichiometry, depending on PIP1 and PIP2 relative
      expression in the cell. All PIP2-PIP1 heterotetrameric species localize at the
      plasma membrane and present the same water transport capacity. Furthermore, the
      contribution of any heterotetrameric assembly to the total water transport
      through the plasma membrane doubles the contribution of PIP2 homotetramers. Our
      results also indicate that plasma membrane water transport can be modulated by
      the coexistence of different tetrameric species and by intracellular pH.
      Moreover, all the tetrameric species present similar cooperativity behavior for
      proton sensing. These findings throw light on the functional properties of PIP
      tetramers, showing that they have flexible stoichiometry dependent on the
      quantity of PIP1 and PIP2 molecules available. This represents, to our knowledge,
      a novel regulatory mechanism to adjust water transport across the plasma
      membrane. 

PMID- 27028642
TI  - Stochastic Model of Gap Junctions Exhibiting Rectification and Multiple Closed
      States of Slow Gates.
AB  - Gap-junction (GJ) channels formed from connexin (Cx) proteins provide direct
      pathways for electrical and metabolic cell-cell communication. Earlier, we
      developed a stochastic 16-state model (S16SM) of voltage gating of the GJ channel
      containing two pairs of fast and slow gates, each operating between open (o) and
      closed (c) states. However, experimental data suggest that gates may in fact
      contain two or more closed states. We developed a model in which the slow gate
      operates according to a linear reaction scheme, o<->c1<->c2, where c1 and c2 are
      initial-closed and deep-closed states that both close the channel fully, whereas
      the fast gate operates between the open state and the closed state and exhibits a
      residual conductance. Thus, we developed a stochastic 36-state model (S36SM) of
      GJ channel gating that is sensitive to transjunctional voltage (Vj). To
      accelerate simulation and eliminate noise in simulated junctional conductance
      (gj) records, we transformed an S36SM into a Markov chain 36-state model (MC36SM)
      of GJ channel gating. This model provides an explanation for well-established
      experimental data, such as delayed gj recovery after Vj gating, hysteresis of gj
      Vj dependence, and the low ratio of functional channels to the total number of GJ
      channels clustered in junctional plaques, and it has the potential to describe
      chemically mediated gating, which cannot be reflected using an S16SM. The MC36SM,
      when combined with global optimization algorithms, can be used for automated
      estimation of gating parameters including probabilities of c1<->c2 transitions
      from experimental gj-time and gj-Vj dependencies. 

PMID- 27028643
TI  - Multiscale Simulations Reveal Key Aspects of the Proton Transport Mechanism in
      the ClC-ec1 Antiporter.
AB  - Multiscale reactive molecular dynamics simulations are used to study proton
      transport through the central region of ClC-ec1, a widely studied ClC transporter
      that enables the stoichiometric exchange of 2 Cl(-) ions for 1 proton (H(+)). It
      has long been known that both Cl(-) and proton transport occur through partially
      congruent pathways, and that their exchange is strictly coupled. However, the
      nature of this coupling and the mechanism of antiporting remain topics of debate.
      Here multiscale simulations have been used to characterize proton transport
      between E203 (Glu(in)) and E148 (Glu(ex)), the internal and external intermediate
      proton binding sites, respectively. Free energy profiles are presented,
      explicitly accounting for the binding of Cl(-) along the central pathway, the
      dynamically coupled hydration changes of the central region, and conformational
      changes of Glu(in) and Glu(ex). We find that proton transport between Glu(in) and
      Glu(ex) is possible in both the presence and absence of Cl(-) in the central
      binding site, although it is facilitated by the anion presence. These results
      support the notion that the requisite coupling between Cl(-) and proton transport
      occurs elsewhere (e.g., during proton uptake or release). In addition, proton
      transport is explored in the E203K mutant, which maintains proton permeation
      despite the substitution of a basic residue for Glu(in). This collection of
      calculations provides for the first time, to our knowledge, a detailed picture of
      the proton transport mechanism in the central region of ClC-ec1 at a molecular
      level.

PMID- 27028644
TI  - Mechanisms for Two-Step Proton Transfer Reactions in the Outward-Facing Form of
      MATE Transporter.
AB  - Bacterial pathogens or cancer cells can acquire multidrug resistance, which
      causes serious clinical problems. In cells with multidrug resistance, various
      drugs or antibiotics are extruded across the cell membrane by multidrug
      transporters. The multidrug and toxic compound extrusion (MATE) transporter is
      one of the five families of multidrug transporters. MATE from Pyrococcus furiosus
      uses H(+) to transport a substrate from the cytoplasm to the outside of a cell.
      Crystal structures of MATE from P. furiosus provide essential information on the
      relevant H(+)-binding sites (D41 and D184). Hybrid quantum mechanical/molecular
      mechanical simulations and continuum electrostatic calculations on the crystal
      structures predict that D41 is protonated in one structure (Straight) and, both
      D41 and D184 protonated in another (Bent). All-atom molecular dynamics
      simulations suggest a dynamic equilibrium between the protonation states of the
      two aspartic acids and that the protonation state affects hydration in the
      substrate binding cavity and lipid intrusion in the cleft between the N- and C
      lobes. This hypothesis is examined in more detail by quantum mechanical/molecular
      mechanical calculations on snapshots taken from the molecular dynamics
      trajectories. We find the possibility of two proton transfer (PT) reactions in
      Straight: the 1st PT takes place between side-chains D41 and D184 through a
      transient formation of low-barrier hydrogen bonds and the 2nd through another
      H(+) from the headgroup of a lipid that intrudes into the cleft resulting in a
      doubly protonated (both D41 and D184) state. The 1st PT affects the local
      hydrogen bond network and hydration in the N-lobe cavity, which would impinge on
      the substrate-binding affinity. The 2nd PT would drive the conformational change
      from Straight to Bent. This model may be applicable to several prokaryotic H(+)
      coupled MATE multidrug transporters with the relevant aspartic acids.

PMID- 27028645
TI  - Cholesterol Partition and Condensing Effect in Phase-Separated Ternary Mixture
      Lipid Multilayers.
AB  - The cholesterol partitioning and condensing effect in the liquid-ordered (Lo) and
      liquid-disordered (Ld) phases were systematically investigated for ternary
      mixture lipid multilayers consisting of 1:1 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine/1,2-dioleoyl-sn-glycero-3-phosphocholine with varying
      concentrations of cholesterol. X-ray lamellar diffraction was used to deduce the
      electron density profiles of each phase. The cholesterol concentration in each
      phase was quantified by fitting of the electron density profiles with a newly
      invented basic lipid profile scaling method that minimizes the number of fitting
      parameters. The obtained cholesterol concentration in each phase versus total
      cholesterol concentration in the sample increases linearly for both phases. The
      condensing effect of cholesterol in ternary lipid mixtures was evaluated in terms
      of phosphate-to-phosphate distances, which together with the estimated
      cholesterol concentration in each phase was converted into an average area per
      molecule. In addition, the cholesterol position was determined to a precision of
      (+/-0.7A) and an increase of disorder in the lipid packing in the Lo phase was
      observed for total cholesterol concentration of 20~30%.

PMID- 27028647
TI  - Reversible Unfolding of Rhomboid Intramembrane Proteases.
AB  - Denaturant-induced unfolding of helical membrane proteins provides insights into
      their mechanism of folding and domain organization, which take place in the
      chemically heterogeneous, anisotropic environment of a lipid membrane. Rhomboid
      proteases are intramembrane proteases that play key roles in various diseases.
      Crystal structures have revealed a compact helical bundle with a buried active
      site, which requires conformational changes for the cleavage of transmembrane
      substrates. A dimeric form of the rhomboid protease has been shown to be
      important for activity. In this study, we examine the mechanism of refolding for
      two distinct rhomboids to gain insight into their secondary structure-activity
      relationships. Although helicity is largely abolished in the unfolded states of
      both proteins, unfolding is completely reversible for HiGlpG but only partially
      reversible for PsAarA. Refolding of both proteins results in reassociation of the
      dimer, with a 90% regain of catalytic activity for HiGlpG but only a 70% regain
      for PsAarA. For both proteins, a broad, gradual transition from the native,
      folded state to the denatured, partly unfolded state was revealed with the aid of
      circular dichroism spectroscopy as a function of denaturant concentration, thus
      arguing against a classical two-state model as found for many globular soluble
      proteins. Thermal denaturation has irreversible destabilizing effects on both
      proteins, yet reveals important functional details regarding substrate
      accessibility to the buried active site. This concerted biophysical and
      functional analysis demonstrates that HiGlpG, with a simple six-transmembrane
      segment organization, is more robust than PsAarA, which has seven predicted
      transmembrane segments, thus rendering HiGlpG amenable to in vitro studies of
      membrane-protein folding.

PMID- 27028646
TI  - A Role for Weak Electrostatic Interactions in Peripheral Membrane Protein
      Binding.
AB  - Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (BtPI-PLC)
      is a secreted virulence factor that binds specifically to phosphatidylcholine
      (PC) bilayers containing negatively charged phospholipids. BtPI-PLC carries a
      negative net charge and its interfacial binding site has no obvious cluster of
      basic residues. Continuum electrostatic calculations show that, as expected,
      nonspecific electrostatic interactions between BtPI-PLC and membranes vary as a
      function of the fraction of anionic lipids present in the bilayers. Yet they are
      strikingly weak, with a calculated DeltaGel below 1 kcal/mol, largely due to a
      single lysine (K44). When K44 is mutated to alanine, the equilibrium dissociation
      constant for small unilamellar vesicles increases more than 50 times (~2.4
      kcal/mol), suggesting that interactions between K44 and lipids are not merely
      electrostatic. Comparisons of molecular-dynamics simulations performed using
      different lipid compositions reveal that the bilayer composition does not affect
      either hydrogen bonds or hydrophobic contacts between the protein interfacial
      binding site and bilayers. However, the occupancies of cation-pi interactions
      between PC choline headgroups and protein tyrosines vary as a function of PC
      content. The overall contribution of basic residues to binding affinity is also
      context dependent and cannot be approximated by a rule-of-thumb value because
      these residues can contribute to both nonspecific electrostatic and short-range
      protein-lipid interactions. Additionally, statistics on the distribution of basic
      amino acids in a data set of membrane-binding domains reveal that weak
      electrostatics, as observed for BtPI-PLC, might be a less unusual mechanism for
      peripheral membrane binding than is generally thought.

PMID- 27028648
TI  - Structural Influences: Cholesterol, Drug, and Proton Binding to Full-Length
      Influenza A M2 Protein.
AB  - The structure and functions of the M2 protein from Influenza A are sensitive to
      pH, cholesterol, and the antiinfluenza drug Amantadine. This is a tetrameric
      membrane protein of 97 amino-acid residues that has multiple functions, among
      them as a proton-selective channel and facilitator of viral budding, replacing
      the need for the ESCRT proteins that other viruses utilize. Here, various amino
      acid-specific-labeled samples of the full-length protein were prepared and mixed,
      so that only interresidue (13)C-(13)C cross peaks between two differently labeled
      proteins representing interhelical interactions are observed. This channel is
      activated at slightly acidic pH values in the endosome when the His(37) residues
      in the middle of the transmembrane domain take on a +2 or +3 charged state.
      Changes observed here in interhelical distances in the N-terminus can be
      accounted for by modest structural changes, and no significant changes in
      structure were detected in the C-terminal portion of the channel upon activation
      of the channel. Amantadine, which blocks proton conductance by binding in the
      aqueous pore near the N-terminus, however, significantly modifies the tetrameric
      structure on the opposite side of the membrane. The interactions between the
      juxtamembrane amphipathic helix of one monomer and its neighboring monomer
      observed in the absence of drug are disrupted in its presence. However, the
      addition of cholesterol prevents this structural disruption. In fact, strong
      interactions are observed between cholesterol and residues in the amphipathic
      helix, accounting for cholesterol binding adjacent to a native palmitoylation
      site and near to an interhelix crevice that is typical of cholesterol binding
      sites. The resultant stabilization of the amphipathic helix deep in the bilayer
      interface facilitates the bilayer curvature that is essential for viral budding.

PMID- 27028649
TI  - Fibrin Fiber Stiffness Is Strongly Affected by Fiber Diameter, but Not by
      Fibrinogen Glycation.
AB  - The major structural component of a blood clot is a mesh of fibrin fibers. Our
      goal was to determine whether fibrinogen glycation and fibrin fiber diameter have
      an effect on the mechanical properties of single fibrin fibers. We used a
      combined atomic force microscopy/fluorescence microscopy technique to determine
      the mechanical properties of individual fibrin fibers formed from blood plasma.
      Blood samples were taken from uncontrolled diabetic patients as well as age-,
      gender-, and body-mass-index-matched healthy individuals. The patients then
      underwent treatment to control blood glucose levels before end blood samples were
      taken. The fibrinogen glycation of the diabetic patients was reduced from 8.8 to
      5.0 mol glucose/mol fibrinogen, and the healthy individuals had a mean fibrinogen
      glycation of 4.0 mol glucose/mol fibrinogen. We found that fibrinogen glycation
      had no significant systematic effect on single-fiber modulus, extensibility, or
      stress relaxation times. However, we did find that the fiber modulus, Y, strongly
      decreases with increasing fiber diameter, D, as Y?D(-1.6). Thin fibers can be 100
      times stiffer than thick fibers. This is unusual because the modulus is a
      material constant and should not depend on the sample dimensions (diameter) for
      homogeneous materials. Our finding, therefore, implies that fibrin fibers do not
      have a homogeneous cross section of uniformly connected protofibrils, as is
      commonly thought. Instead, the density of protofibril connections, rhoPb,
      strongly decreases with increasing diameter, as rhoPb?D(-1.6). Thin fibers are
      denser and/or have more strongly connected protofibrils than thick fibers. This
      implies that it is easier to dissolve clots that consist of fewer thick fibers
      than those that consist of many thin fibers, which is consistent with
      experimental and clinical observations.

PMID- 27028650
TI  - Bacterial Flagellar Motor Switch in Response to CheY-P Regulation and Motor
      Structural Alterations.
AB  - The bacterial flagellar motor (BFM) is a molecular machine that rotates the
      helical filaments and propels the bacteria swimming toward favorable conditions.
      In our previous works, we built a stochastic conformational spread model to
      explain the dynamic and cooperative behavior of BFM switching. Here, we extended
      this model to test whether it can explain the latest experimental observations
      regarding CheY-P regulation and motor structural adaptivity. We show that our
      model predicts a strong correlation between rotational direction and the number
      of CheY-Ps bound to the switch complex, in agreement with the latest finding from
      Fukuoka et al. It also predicts that the switching sensitivity of the BFM can be
      fine-tuned by incorporating additional units into the switch complex, as recently
      demonstrated by Yuan et al., who showed that stoichiometry of FliM undergoes
      dynamic change to maintain ultrasensitivity in the motor switching response. In
      addition, by locking some rotor switching units on the switch complex into the
      stable clockwise-only conformation, our model has accurately simulated recent
      experiments expressing clockwise-locked FliG(DeltaPAA) into the switch complex
      and reproduced the increased switching rate of the motor.

PMID- 27028651
TI  - Determining Physical Properties of the Cell Cortex.
AB  - Actin and myosin assemble into a thin layer of a highly dynamic network
      underneath the membrane of eukaryotic cells. This network generates the forces
      that drive cell- and tissue-scale morphogenetic processes. The effective material
      properties of this active network determine large-scale deformations and other
      morphogenetic events. For example, the characteristic time of stress relaxation
      (the Maxwell time tauM) in the actomyosin sets the timescale of large-scale
      deformation of the cortex. Similarly, the characteristic length of stress
      propagation (the hydrodynamic length lambda) sets the length scale of slow
      deformations, and a large hydrodynamic length is a prerequisite for long-ranged
      cortical flows. Here we introduce a method to determine physical parameters of
      the actomyosin cortical layer in vivo directly from laser ablation experiments.
      For this we investigate the cortical response to laser ablation in the one-cell
      stage Caenorhabditis elegans embryo and in the gastrulating zebrafish embryo.
      These responses can be interpreted using a coarse-grained physical description of
      the cortex in terms of a two-dimensional thin film of an active viscoelastic gel.
      To determine the Maxwell time tauM, the hydrodynamic length lambda, the ratio of
      active stress zetaDeltaMU, and per-area friction gamma, we evaluated the response
      to laser ablation in two different ways: by quantifying flow and density fields
      as a function of space and time, and by determining the time evolution of the
      shape of the ablated region. Importantly, both methods provide best-fit physical
      parameters that are in close agreement with each other and that are similar to
      previous estimates in the two systems. Our method provides an accurate and robust
      means for measuring physical parameters of the actomyosin cortical layer. It can
      be useful for investigations of actomyosin mechanics at the cellular-scale, but
      also for providing insights into the active mechanics processes that govern
      tissue-scale morphogenesis.

PMID- 27028652
TI  - Actin-Regulator Feedback Interactions during Endocytosis.
AB  - Endocytosis mediated by clathrin, a cellular process by which cells internalize
      membrane receptors and their extracellular ligands, is an important component of
      cell signaling regulation. Actin polymerization is involved in endocytosis in
      varying degrees depending on the cellular context. In yeast, clathrin-mediated
      endocytosis requires a pulse of polymerized actin and its regulators, which
      recruit and activate the Arp2/3 complex. In this article, we seek to identify the
      main protein-protein interactions that 1) cause actin and its regulators to
      appear in pulses, and 2) determine the effects of key mutations and drug
      treatments on actin and regulator assembly. We perform a joint
      modeling/experimental study of actin and regulator dynamics during endocytosis in
      the budding yeast Saccharomyces cerevisiae. We treat both a stochastic model that
      grows an explicit three-dimensional actin network, and a simpler two-variable
      Fitzhugh-Nagumo type model. The models include a negative-feedback interaction of
      F-actin onto the Arp2/3 regulators. Both models explain the pulse time courses
      and the effects of interventions on actin polymerization: the surprising increase
      in the peak F-actin count caused by reduced regulator branching activity, the
      increase in F-actin resulting from slowing of actin disassembly, and the
      increased Arp2/3 regulator lifetime resulting from latrunculin treatment. In
      addition, they predict that decreases in the regulator branching activity lead to
      increases in accumulation of regulators, and we confirmed this prediction with
      experiments on yeast harboring mutations in the Arp2/3 regulators, using
      quantitative fluorescence microscopy. Our experimental measurements suggest that
      the regulators act quasi-independently, in the sense that accumulation of a
      particular regulator is most strongly affected by mutations of that regulator, as
      opposed to the others. 

PMID- 27028653
TI  - Dynamic Regulation of alpha-Actinin's Calponin Homology Domains on F-Actin.
AB  - alpha-Actinin is an essential actin cross-linker involved in cytoskeletal
      organization and dynamics. The molecular conformation of alpha-actinin's actin
      binding domain (ABD) regulates its association with actin and thus mutations in
      this domain can lead to severe pathogenic conditions. A point mutation at lysine
      255 in human alpha-actinin-4 to glutamate increases the binding affinity
      resulting in stiffer cytoskeletal structures. The role of different ABD
      conformations and the effect of K255E mutation on ABD conformations remain
      elusive. To evaluate the impact of K255E mutation on ABD binding to actin we use
      all-atom molecular dynamics and free energy calculation methods and study the
      molecular mechanism of actin association in both wild-type alpha-actinin and in
      the K225E mutant. Our models illustrate that the strength of actin association is
      indeed sensitive to the ABD conformation, predict the effect of K255E mutation-
      based on simulations with the K237E mutant chicken alpha-actinin--and evaluate
      the mechanism of alpha-actinin binding to actin. Furthermore, our simulations
      showed that the calmodulin domain binding to the linker region was important for
      regulating the distance between actin and ABD. Our results provide valuable
      insights into the molecular details of this critical cellular phenomenon and
      further contribute to an understanding of cytoskeletal dynamics in health and
      disease.

PMID- 27028655
TI  - Impact of dentine hypersensitivity on oral health-related quality of life in
      individuals receiving supportive periodontal care.
AB  - AIM: To determine the prevalence and impact of dentine hypersensitivity (DH) on
      oral health-related quality of life (OHRQoL) in individuals receiving supportive
      periodontal care (SPC). MATERIALS AND METHODS: One hundred and two adults
      receiving SPC were recruited for a cross-sectional study. Subjects were
      categorized into those who self-reported DH (DH1) or did not (DH0). Impact of DH
      on OHRQoL was assessed using the Chinese Condition-Specific Oral Impact on Daily
      Performance questionnaire (CS-OIDP). Evaluation of DH included tactile
      stimulation followed by air-blast, and recorded using a Visual Analogue Scale
      (VAS). RESULTS: Sixty-one (59.8%) subjects self-reported DH with mean air-blast
      VAS score of 29.4 +/- 21.3 mm and mean tactile-stimulation VAS score of 10.9 +/-
      14.7 mm. Fifty (49%) subjects reported impact on OHRQoL (mean CS-OIDP score = 4.7
      +/- 6.3). The most affected performance was cleaning the mouth (35.3%). Positive
      expression of DH and worse OHRQoL were associated with higher air-blast and
      tactile-stimulation VAS scores, and use of desensitizing agents. The minimally
      important difference (MID) in CS-OIDP scores was 2.0 points. Approximately 30% of
      the subjects reported CS-OIDP scores above the MID. CONCLUSIONS: Dentine
      hypersensitivity affects OHRQoL in patients undergoing SPC. The extent of impact
      was associated with severity of DH.

PMID- 27028654
TI  - Diagonally Scanned Light-Sheet Microscopy for Fast Volumetric Imaging of Adherent
      Cells.
AB  - In subcellular light-sheet fluorescence microscopy (LSFM) of adherent cells,
      glass substrates are advantageously rotated relative to the excitation and
      emission light paths to avoid glass-induced optical aberrations. Because cells
      are spread across the sample volume, three-dimensional imaging requires a light
      sheet with a long propagation length, or rapid sample scanning. However, the
      former degrades axial resolution and/or optical sectioning, while the latter
      mechanically perturbs sensitive biological specimens on pliant biomimetic
      substrates (e.g., collagen and basement membrane). Here, we use aberration-free
      remote focusing to diagonally sweep a narrow light-sheet along the sample
      surface, enabling multicolor imaging with high spatiotemporal resolution.
      Further, we implement a dithered Gaussian lattice to minimize sample-induced
      illumination heterogeneities, significantly improving signal uniformity. Compared
      with mechanical sample scanning, we drastically reduce sample oscillations,
      allowing us to achieve volumetric imaging at speeds of up to 3.5 Hz for thousands
      of Z-stacks. We demonstrate the optical performance with live-cell imaging of
      microtubule and actin cytoskeletal dynamics, phosphoinositide signaling, clathrin
      mediated endocytosis, polarized blebbing, and endocytic vesicle sorting. We
      achieve three-dimensional particle tracking of clathrin-associated structures
      with velocities up to 4.5 MUm/s in a dense intracellular environment, and show
      that such dynamics cannot be recovered reliably at lower volumetric image
      acquisition rates using experimental data, numerical simulations, and theoretical
      modeling.

PMID- 27028656
TI  - Deciphering Noncovalent Interactions Accompanying 7,7,8,8
      Tetracyanoquinodimethane Encapsulation within Biphene[n]arenes: Nucleus
      Independent Chemical Shifts Approach.
AB  - Binding of novel biphene[n]arene hosts to antiaromatic 7,7,8,8
      tetracyanoquinodimethane (TCNQ) are investigated by DFT. Biphene[4]arene favors
      the inclusion complex through noncovalent interactions, such as hydrogen bonding,
      pi-pi stacking, C-H???pi, and C-H???H-C dihydrogen bonding. Donor-acceptor
      complexation renders aromatic character to the guest through charge transfer. The
      formation of TCNQ anionic radicals through supramolecular pi stacking
      significantly influences its chemical and photophysical behavior. Electron
      density reorganization consequent to encapsulation of TCNQ reflects in the shift
      of characteristic vibrations in the IR spectra. The accompanying aromaticities
      arising from the induced ring currents are analyzed by employing nucleus
      independent chemical shifts based profiles. 

PMID- 27028657
TI  - Organ allocation for liver transplantation: One size does not fill all.

PMID- 27028658
TI  - Correction: Prior Hydrologic Disturbance Affects Competition between Aedes
      Mosquitoes via Changes in Leaf Litter.

PMID- 27028659
TI  - Enhanced Photoresponse from Phosphorene-Phosphorene-Suboxide Junction Fashioned
      by Focused Laser Micromachining.
AB  - Enhanced photoresponse is obtained from phosphorene-phosphorene-suboxide. A
      scanning focused laser beam is employed as a straightforward approach to convert
      part of a phosphorene film into phosphorene suboxide, creating a functional
      junction in situ on an optoelectronic device based on phosphorene. As a result,
      the photoelectrical properties of the optoelectronic device are significantly
      improved. 

PMID- 27028660
TI  - Importance of awareness in improving performance of emergency medical services
      (EMS) systems in enhancing traffic safety: A lesson from India.
AB  - OBJECTIVE: India has been slow in implementing a central emergency medical
      services (EMS) system across the country. "108 services" is one of the most
      popular services that is functional under the public-private partnership model.
      Limited available literature shows that despite access to services, many traffic
      crash victims are transported using private vehicles. The objective of this study
      is to understand the effectiveness of 108 services from a traffic safety
      perspective. METHOD: A questionnaire survey is conducted to understand the
      awareness of EMS and their function. Using traffic-related fatalities as the
      dependent variable, a fixed effect panel data model is developed to analyze the
      effectiveness of the 108 services in improving the traffic safety. RESULTS: The
      results from the survey show that, in general, people are not aware of the 108
      services. A majority of the population prefers taking victims to the hospital
      using their personal vehicles or any other vehicles available compared to calling
      an ambulance. Results from panel data analysis show that despite having an
      efficient system, these services failed to make significant improvement in the
      safety of road users in the states in which their services were subscribed.
      DISCUSSION: The lack of awareness of an important safety service is alarming.
      This could be a major reason for lower utilization of 108 services for
      transporting victims of traffic crashes. This article shows the importance of
      having efficient awareness campaigns to improve the efficiency of any similar
      programs that are aimed to enhance the safety of a region.

PMID- 27028661
TI  - Increased distractibility in schizotypy: Independent of individual differences in
      working memory capacity?
AB  - Individuals with schizophrenia typically show increased levels of
      distractibility. This has been attributed to impaired working memory capacity
      (WMC), since lower WMC is typically associated with higher distractibility, and
      schizophrenia is typically associated with impoverished WMC. Here, participants
      performed verbal and spatial serial recall tasks that were accompanied by to-be
      ignored speech tokens. For the few trials wherein one speech token was replaced
      with a different token, impairment was produced to task scores (a deviation
      effect). Participants subsequently completed a schizotypy questionnaire and a WMC
      measure. Higher schizotypy scores were associated with lower WMC (as measured
      with operation span, OSPAN), but WMC and schizotypy scores explained unique
      variance in relation to the mean magnitude of the deviation effect. These results
      suggest that schizotypy is associated with heightened domain-general
      distractibility, but that this is independent of its relationship with WMC.

PMID- 27028662
TI  - Bundled Payment Models for Actinic Keratosis Management.
AB  - IMPORTANCE: Recent legislation encourages alternative payment models, such as
      bundled payments. There are no clear recommendations on bundled payment design,
      and research on bundled payments for dermatologic care is limited. OBJECTIVE: To
      investigate several methods to develop bundled payment models for actinic
      keratosis (AK) management and the likely effect on the cost of AK management.
      DESIGN, SETTING, AND PARTICIPANTS: Cohort cost identification study using claims
      from Highmark Insurance and the MarketScan Commercial Claims and Encounters
      databases. Patients with claims for AK during the study period, January 2010 to
      December 2012, were included (N = 118 129). Utilization measures, such as visits
      and procedures, and direct costs were calculated and 8 bundled payment models
      were developed. Indirect costs were not included. MAIN OUTCOMES AND MEASURES: The
      actual health care costs and theoretical cost differences for the bundled
      payments. Costs are reported in 2012 US dollars and were adjusted for inflation.
      The proportion of patients and clinicians with annual AK claim costs less than or
      equal to the bundled payments were calculated. RESULTS: Eight bundled payment
      models were developed and 2, based on the 75th percentile payment, did not result
      in theoretical savings for any of the patient samples (increased annual spending
      of $1.04 million to $6.88 million). The median-based payment without adjustments
      resulted in the largest theoretical savings (decreased spending of $2.22 million
      to $6.43 million). In contrast, the mean-based payment with adjustments resulted
      in the smallest theoretical savings. The median-based with indirect payment
      (65.2% for patients and 62.0% for clinicians) and mean-based adjusted payments,
      with (68.9% and 66.2%) and without (68.1% and 65.6%) discount, were equal to or
      greater than the actual health care costs for similar proportions of patients and
      clinicians, respectively. In addition, both resulted in a decrease in overall
      health care costs for the patient cohort. CONCLUSIONS AND RELEVANCE: It is
      important to consider alternative payment models, such as bundled payments, in
      preparation for payment reform. The dermatology profession needs to understand
      disease management in dollar terms to advocate on behalf of clinicians and
      patients for fair and reasonable reimbursement, regardless of payment type.

PMID- 27028663
TI  - Invasive fungal rhinosinusitis with palatal erosion in an elderly edentulous
      patient with uncontrolled diabetes: report of a rare case.
AB  - OBJECTIVES: To report a rare case of chronic invasive fungal rhinosinusitis with
      palatal erosion. BACKGROUND: Restoring and maintaining oral health of diabetic
      elderly patients with increased risk of infections is a challenge to the dentist.
      Patients suffering from uncontrolled diabetes are susceptible to fungal
      infections. Palatal erosion due to fungal rhinosinusitis is rare. MATERIALS AND
      METHODS: Case report of a 65 years old illiterate female patient from low socio
      economic strata, suffering from uncontrolled diabetes and poor systemic health
      presenting with chronic invasive fungal rhinosinusitis leading to palatal
      erosion. CONCLUSION: Such a case is a diagnostic challenge to a dentist.
      Therefore understanding the disease process and its possible outcomes is
      desirable. The treatment warrants a multidisciplinary approach.

PMID- 27028665
TI  - Electropolymerized Star-Shaped Benzotrithiophenes Yield pi-Conjugated
      Hierarchical Networks with High Areal Capacitance.
AB  - High-surface-area pi-conjugated polymeric networks have the potential to lend
      outstanding capacitance to supercapacitors because of the pronounced faradaic
      processes that take place across the dense intimate interface between active
      material and electrolytes. In this report, we describe how benzo[1,2-b:3,4-b':5,6
      b"]trithiophene (BTT) and tris(ethylenedioxythiophene)benzo[1,2-b:3,4-b':5,6
      b"]trithiophene (TEBTT) can serve as 2D (trivalent) building blocks in the
      development of electropolymerized hierarchical pi-conjugated frameworks with
      particularly high areal capacitance. In comparing electropolymerized networks of
      BTT, TEBTT, and their copolymers with EDOT, we show that TEBTT/EDOT-based
      copolymers, i.e., P(TEBTT/EDOT), can achieve higher areal capacitance (e.g., as
      high as 443.8 mF cm(-2) at 1 mA cm(-2)) than those achieved by their respective
      homopolymers (PTEBTT and PEDOT) in the same experimental conditions of
      electrodeposition (PTEBTT: 271.1 mF cm(-2) (at 1 mA cm(-2)) and PEDOT: 12.1 mF
      cm(-2) (at 1 mA cm(-2))). For example, P(TEBTT/EDOT)-based frameworks synthesized
      in a 1:1 monomer-to-comonomer ratio show a ca. 35* capacitance improvement over
      PEDOT. The high areal capacitance measured for P(TEBTT/EDOT)-based frameworks can
      be explained by the open, highly porous hierarchical morphologies formed during
      the electropolymerization step. With >70% capacitance retention over 1000 cycles
      (up to 89% achieved), both PTEBTT- and P(TEBTT/EDOT)-based frameworks are
      resilient to repeated electrochemical cycling and can be considered promising
      systems for high life cycle capacitive electrode applications.

PMID- 27028664
TI  - The ubiquitin proteasomal system: a potential target for the management of
      Alzheimer's disease.
AB  - The cellular quality control system degrades abnormal or misfolded proteins and
      consists of three different mechanisms: the ubiquitin proteasomal system (UPS),
      autophagy and molecular chaperones. Any disturbance in this system causes
      proteins to accumulate, resulting in neurodegenerative diseases such as
      amyotrophic lateral sclerosis, Alzheimer's disease (AD), Parkinson's disease,
      Huntington's disease and prion or polyglutamine diseases. Alzheimer's disease is
      currently one of the most common age-related neurodegenerative diseases. However,
      its exact cause and pathogenesis are unknown. Currently approved medications for
      AD provide symptomatic relief; however, they fail to influence disease
      progression. Moreover, the components of the cellular quality control system
      represent an important focus for the development of targeted and potent therapies
      for managing AD. This review aims to evaluate whether existing evidence supports
      the hypothesis that UPS impairment causes the early pathogenesis of
      neurodegenerative disorders. The first part presents basic information about the
      UPS and its molecular components. The next part explains how the UPS is involved
      in neurodegenerative disorders. Finally, we emphasize how the UPS influences the
      management of AD. This review may help in the design of future UPS-related
      therapies for AD.

PMID- 27028666
TI  - A prospective study comparing prophylactic gastrostomy to nutritional counselling
      with a therapeutic feeding tube if required in head and neck cancer patients
      undergoing chemoradiotherapy in Thai real-world practice.
AB  - BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for head
      and neck (HN) cancer patients. Most patients experience malnutrition and weight
      loss during treatment because of mucositis and difficulty in swallowing.
      Prevention of malnutrition may allow more patients to complete their treatment.
      The present study aimed to examine whether prophylactic gastrostomy tube (PGT)
      could reduce treatment interruption, prevent malnutrition and maintain quality of
      life, especially in Thai patients who generally do not accept feeding tubes.
      METHODS: A prospective study was performed on HN cancer patients undergoing CRT
      at a tertiary hospital in Thailand (n = 95). Before starting CRT, all patients
      received nutritional assessment and were counselled about the risks and benefits
      of PGT. According to patient discretion, they chose to have a PGT (experimental
      group) or only nutritional counselling with a therapeutic feeding tube if
      required (control group). During CRT, weight, degree of mucositis, delayed
      chemotherapy and/or radiotherapy, and nutritional status were recorded. Quality
      of life (Functional Assessment of Cancer Therapy - Head and Neck Scale; FACT-H&N)
      was compared between two groups. RESULTS: There was no significant difference in
      the rates of delayed treatment. Mean weight loss was 3.1 and 4.8 kg in the
      experimental and control groups, respectively (P = 0.04). A higher proportion of
      patients in the control group experienced >=10% weight loss (24% versus 4%; P =
      0.03). In terms of quality of life, no significant difference in FACT-H&N score
      was found. CONCLUSIONS: The results of the present study suggest that PGT
      provided similar quality of life without a reduction in treatment interruption.
      However, patients with PGT had significantly less weight loss (P = 0.04) during
      CRT.

PMID- 27028667
TI  - Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain
      Abnormalities.
AB  - The current outbreak of Zika virus (ZIKV) infection has been associated with an
      apparent increased risk of congenital microcephaly. We describe a case of a
      pregnant woman and her fetus infected with ZIKV during the 11th gestational week.
      The fetal head circumference decreased from the 47th percentile to the 24th
      percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in
      maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation,
      substantial brain abnormalities were detected on ultrasonography and magnetic
      resonance imaging (MRI) without the presence of microcephaly or intracranial
      calcifications. On postmortem analysis of the fetal brain, diffuse cerebral
      cortical thinning, high ZIKV RNA loads, and viral particles were detected, and
      ZIKV was subsequently isolated. 

PMID- 27028668
TI  - Yeast as a tool to select inhibitors of the cullin deneddylating enzyme Csn5.
AB  - The CSN complex plays a key role in various cellular pathways: through a
      metalloprotease activity of its Csn5 deneddylating enzyme, it regulates the
      activity of Cullin-RING ligases (CRLs). Indeed, Csn5 has been found amplified in
      many tumors, but, due to its pleiotropic effects, it is difficult to dissect its
      function and the involvement in cancer progression. Moreover, while growing
      evidences point to the neddylation function as a good target for drug
      development; specific inhibitors have not yet been developed for the CSN. Here,
      we propose the yeast Saccharomyces cerevisiae as a model system to screen
      libraries of small molecules as inhibitors of cullins deneddylation, taking
      advantage of the unique feature of this organism to survive without a functional
      CSN5 gene and to accumulate a fully neddylated cullin substrate. By combining
      molecular modeling and simple genetic tools, we were able to identify two small
      molecular fragments as selective inhibitors of Csn5 deneddylation function. 

PMID- 27028669
TI  - Basic Physicochemical Properties of Polyethylene Glycol Coated Gold Nanoparticles
      that Determine Their Interaction with Cells.
AB  - A homologous nanoparticle library was synthesized in which gold nanoparticles
      were coated with polyethylene glycol, whereby the diameter of the gold cores, as
      well as the thickness of the shell of polyethylene glycol, was varied. Basic
      physicochemical parameters of this two-dimensional nanoparticle library, such as
      size, zeta-potential, hydrophilicity, elasticity, and catalytic activity ,were
      determined. Cell uptake of selected nanoparticles with equal size yet varying
      thickness of the polymer shell and their effect on basic structural and
      functional cell parameters was determined. Data indicates that thinner, more
      hydrophilic coatings, combined with the partial functionalization with quaternary
      ammonium cations, result in a more efficient uptake, which relates to significant
      effects on structural and functional cell parameters.

PMID- 27028670
TI  - Successful treatment of rosacea fulminans in a 59-year-old woman with macrolide
      antibiotics and prednisone.

PMID- 27028671
TI  - Breakthrough drugs for the interface between psychiatry and neurology.

PMID- 27028672
TI  - Acute kidney injury - nephrology's latest problem child.

PMID- 27028673
TI  - Persistence of solifenacin therapy in patients with overactive bladder in the
      clinical setting: a prospective, multicenter, observational study.
AB  - OBJECTIVES: The aim of this study was to evaluate the persistence with
      solifenacin therapy over a 12-month period in patients with overactive bladder
      (OAB). METHODS: This is a 52-week long, multicenter, prospective, observational
      study. The subjects were individuals >= 18 years old with OAB symptoms for >= 3
      months, characterised by a total OAB Symptom Score (OABSS) of >= 3 and OABSS
      urgency item score of >= 2. Patients were prescribed 5 mg or 10 mg of solifenacin
      once daily for OAB symptoms. Drug persistence, reasons for discontinuation and
      factors related to the persistence were evaluated. RESULTS: A total of 1018
      patients (329 men, 689 women) with a mean age of 59 years were included. The 52
      week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36
      weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for
      discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in
      13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients
      (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94,
      95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month
      period than were younger, male patients. The number of nocturia episodes was
      negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71
      0.97). CONCLUSIONS: There was low persistence (22%) to solifenacin therapy for
      OAB symptoms over a 12-month period. Older patients, female patients and those
      with fewer episodes of nocturia were more persistent to therapy than were others.

PMID- 27028674
TI  - The emergence of frailty may burn out type 2 diabetes-a hypothesis.

PMID- 27028676
TI  - Enabling technologies for robot assisted ultrasound tomography.
AB  - Currently available ultrasound (US) tomography systems suggest utilizing
      cylindrical transducers that can be used for a specific organ. In this paper, our
      focus is on an alternative way of creating US tomographic images that could be
      used for other anatomies and more general applications. This system consists of
      two conventional US probes facing each other while one or several of the
      transducers in one probe can act as the transmitter and the rest as the receiver.
      Aligning the two US probes is a challenging task. To address this issue, we
      propose a robot assisted US tomography system in which one probe is operated
      freehanded and another by a robotic arm. In this paper, enabling technologies for
      this system are described. With the current prototype, a reconstruction precision
      of 4.12, 1.73, and 2.23 mm for the three calibrations, and an overall alignment
      repeatability in the range of 5-9 mm were achieved. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27028675
TI  - Structural determinants in bacterial 2-keto-3-deoxy-D-gluconate dehydrogenase
      KduD for dual-coenzyme specificity.
AB  - Short-chain dehydrogenase/reductase (SDR) is distributed in many organisms, from
      bacteria to humans, and has significant roles in metabolism of carbohydrates,
      lipids, amino acids, and other biomolecules. An important intermediate in acidic
      polysaccharide metabolism is 2-keto-3-deoxy-d-gluconate (KDG). Recently, two
      short and long loops in Sphingomonas KDG-producing SDR enzymes (NADPH-dependent
      A1-R and NADH-dependent A1-R') involved in alginate metabolism were shown to be
      crucial for NADPH or NADH coenzyme specificity. Two SDR family enzymes-KduD from
      Pectobacterium carotovorum (PcaKduD) and DhuD from Streptococcus pyogenes
      (SpyDhuD)-prefer NADH as coenzyme, although only PcaKduD can utilize both NADPH
      and NADH. Both enzymes reduce 2,5-diketo-3-deoxy-d-gluconate to produce KDG.
      Tertiary and quaternary structures of SpyDhuD and PcaKduD and its complex with
      NADH were determined at high resolution (approximately 1.6 A) by X-ray
      crystallography. Both PcaKduD and SpyDhuD consist of a three-layered structure,
      alpha/beta/alpha, with a coenzyme-binding site in the Rossmann fold; similar to
      enzymes A1-R and A1-R', both arrange the two short and long loops close to the
      coenzyme-binding site. The primary structures of the two loops in PcaKduD and
      SpyDhuD were similar to those in A1-R' but not A1-R. Charge neutrality and
      moderate space at the binding site of the nucleoside ribose 2' coenzyme region
      were determined to be structurally crucial for dual-coenzyme specificity in
      PcaKduD by structural comparison of the NADH- and NADPH-specific SDR enzymes. The
      corresponding site in SpyDhuD was negatively charged and spatially shallow. This
      is the first reported study on structural determinants in SDR family KduD related
      to dual-coenzyme specificity. Proteins 2016; 84:934-947. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27028678
TI  - From the President.

PMID- 27028679
TI  - Thirty-Five Years and Going Strong!

PMID- 27028680
TI  - Bowel Regimen Following Scoliosis Repair.

PMID- 27028681
TI  - NAON Position Statement: Promoting Musculoskeletal Health Through Physical
      Activity for All Children and Adolescents.

PMID- 27028683
TI  - Validation of the Nurses' Perception of Patient Rounding Scale: An Exploratory
      Study of the Influence of Shift Work on Nurses' Perception of Patient Rounding.
AB  - Hourly rounds have re-emerged as standard practice among nurses in acute care
      settings, and there is the need to identify nurses' perceptions regarding this
      practice. Further use of the Nurses' Perception of Patient Rounding Scale (NPPRS)
      is needed to further validate this new instrument. In addition, there exists a
      dearth of literature that examines the impact of hours worked and shift on
      nurses' perceptions of patient rounding. The purpose of this descriptive study
      was to explore nurses' perception of the required practice of patient rounding,
      to examine the influence of nurses' shift on nurses' perception of rounding
      practice, and to provide additional psychometric support for the NPPRS. The
      NPPRS, a 42-item scale in 5-point Likert format, and a demographic information
      sheet were used in the study. The NPPRS yields three subscales: communication,
      patient benefits, and nurse benefits. Using a convenience sample of anonymous
      nurse participants, 76 nurses from five medical-surgical units at a medical
      center in the northeast corridor of the United States participated in the study.
      Further psychometric support for the NPPRS was demonstrated. Excellent
      reliability coefficients via Cronbach's alpha for the total scale (0.91) and each
      of the subscales were obtained. A statistically significant difference was noted
      among nurses working 8 hours versus 12 hours or combined 8- and 12-hour
      workloads. Perceptions of nurse benefits were statistically significantly higher
      for nurses working 8 hours. In addition, results indicated that nurses perceived
      rounding to be more beneficial to their own practice than to patients. Analyses
      revealed that leadership support was instrumental in successful rounding
      practice. Further support for the NPPRS was obtained through this study. Strong
      nursing leadership, supportive of rounding, is essential for successful rounding.
      Further research should examine the efficacy of nurse rounding-developed
      protocols specific to the shift and unit of nursing practice. 

PMID- 27028684
TI  - Bracing in Ponseti Clubfoot Treatment: Improving Parental Adherence Through an
      Innovative Health Education Intervention.
AB  - Clubfoot is the most common musculoskeletal birth defect, characterized by
      abnormal tendon and muscle development, leading to abnormal bone alignment of the
      feet. The Ponseti method is considered the gold standard in clubfoot treatment,
      and consists of a series of plaster castings, followed by 4 years of brace use.
      The most common cause of clubfoot relapse is nonadherence with the bracing
      protocol by the child's caretakers. The purpose of this study was to design,
      implement, and evaluate an educational bracing program for parents of children
      with clubfoot in an effort to improve bracing adherence. The educational bracing
      program for parents of children with clubfoot was designed with incorporation of
      findings from previous research, adult teaching methodology, and parental
      feedback. An educational brochure and a practice doll were created for use in
      educational sessions with parents during routine treatment visits. Two
      educational sessions were conducted with a health educator, employing identical
      questionnaires to assess changes in parental knowledge and skills upon completion
      of the program. Thirty parents completed the educational bracing program, and the
      majority reported increased knowledge and self-efficacy regarding the bracing
      protocol of the Ponseti method. In addition, the health practitioners who
      conducted the educational sessions witnessed an improved ability of all parents
      to apply the brace as directed, and to recognize and correct improper fit.
      Completion of the educational program by the parents resulted in immediate
      improvements in knowledge and skills related to clubfoot bracing. Given that
      noncompliance to the bracing protocol is the most common cause of clubfoot
      relapse, these immediate effects of the educational program are promising not
      only because they encourage proper brace use, but because these immediate
      improvements have the potential to reduce future rates of clubfoot relapse. 

PMID- 27028686
TI  - To Assess Prerequisites Before an Implementation Strategy in an Orthopaedic
      Department in Sweden.
AB  - Promoting Action on Research Implementation in Health Services (PARiHS) asserts
      that the success of knowledge implementation relates to multiple factors in a
      complex and dynamic way, and therefore the effects of implementation strategies
      vary by method and context. An instrument based on the PARiHS framework was
      developed to help assess critical factors influencing implementation strategies
      so that strategies can be tailored to promote implementation.The purpose of this
      study was to use the Evaluation Before Implementation Questionnaire (EBIQ), to
      describe staff perceptions in one orthopaedic department, and to investigate
      differences between wards.Staff members in four different wards at one
      orthopaedic department at a university hospital in Sweden were invited to
      complete a questionnaire related to planning for the implementation of a clinical
      practice guideline. The 23 items in the EBIQ were expected to capture staff
      perceptions about the evidence, context, and facilitation factors that influence
      the implementation process. Descriptive statistics and differences between wards
      were analyzed. Although the overall response rate was low (n = 49), two of the
      four wards accounted for most of the completed questionnaires (n = 25 and n = 12,
      respectively), enabling a comparison of these wards. We found significant
      differences between respondents' perceptions at the two wards in six items
      regarding context and facilitation in terms of receptiveness to change, forms of
      leadership, and evaluation and presence of feedback and facilitators.The EBIQ
      instrument requires further testing, but there appears to be initial support for
      pre-implementation use of the EBIQ as a means to enhance planning for
      implementation. 

PMID- 27028687
TI  - Enhancing Nurses' Pain Assessment to Improve Patient Satisfaction.
AB  - Patient satisfaction with pain management has increasing importance with Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores tied to
      reimbursement. Previous studies indicate patient satisfaction is influenced by
      staff interactions. This single-group pre/post design study aimed to improve
      satisfaction with pain management in older adults undergoing total joint
      replacement. This was a single-group pre-/posttest design. Nurse (knowledge
      assessment) and patient (American Pain Society Patient Outcomes Questionnaire
      Revised [APS-POQ-R], HCAHPS) responses evaluated pre- and postimplementation of
      the online educational program. Nurse focus group followed intervention. Nurses'
      knowledge improved significantly (p < .006) postintervention. HCAHPS scores (3
      month average) for items reflecting patient satisfaction improved from 70.2 +/-
      9.5 to 73.9 +/- 6.0. APS-POQ-R scores did not change. Focus group comments
      indicated need for education regarding linkages between pain management and
      patient satisfaction. Education on linkages between patient satisfaction and pain
      management can improve outcomes; education on strategies to further improve
      practice may enhance ability to achieve benchmarks. 

PMID- 27028689
TI  - The Effect of Administration Protocol of Subcutaneous Enoxaparin Injection on
      Formation of Ecchymosis.
AB  - Subcutaneous heparin administration is routinely used for many patients in
      orthopaedic clinics. Nurses frequently encounter ecchymosis formation with
      heparin administration. Previous research indicates that the administration
      protocol may have effect on ecchymosis formation. The study was performed to
      determine and compare the effect of three different approaches of subcutaneous
      enoxaparin injection on ecchymosis formation in patients who underwent joint
      replacement surgery. Three protocols were compared: (1) injecting enoxaparin in
      10 seconds, (2) injecting enoxaparin in 30 seconds, and (3) injecting enoxaparin
      in 30 seconds and waiting for an additional 10 seconds before withdrawing the
      needle. Ecchymosis formation was assessed in both size and frequency. Descriptive
      statistics, Kruskal-Wallis analysis, Mann-Whitney U test, and Spearman rank
      correlation test were used to assess the data. The ecchymosis frequency was
      higher in the 10-second administration. Ecchymosis size was smaller when the
      enoxaparin was administered in 30 seconds and the needle was kept in the tissue
      for 10 seconds after injection. The enoxaparin should be administered in a longer
      duration (30 seconds). Keeping the needle in the tissue for 10 seconds may
      further decrease the size but not the incidence of ecchymosis. 

PMID- 27028691
TI  - Symptomatic Patellar Plica in a Runner.

PMID- 27028697
TI  - Nuclear magnetic resonance study of sulfate reorientations in LiNaSO4.
AB  - A nuclear magnetic resonance study of the sulfate ion reorientations in beta
      LiNaSO4 has been carried out. The influence of the SO4 reorientational jumps on
      the quadrupolar interactions of (7)Li nuclei was investigated by a jump
      reorientational model, which has not previously been applied to sulfates. The
      activation energy required for the SO4 reorientations was found to be 0.19 eV. It
      was also revealed that the SO4 reorientational disorder should be associated with
      a small anomaly of a heat capacity at around 600 K, which was previously observed
      experimentally.

PMID- 27028695
TI  - Challenges in nourishing the intrauterine growth-restricted foetus - Lessons
      learned from studies in the intrauterine growth-restricted foetal sheep.
AB  - Previous attempts to improve growth and development of the intrauterine growth
      restricted (IUGR) foetus during pregnancy have not worked or caused harm. Our
      research identifies tissue-specific mechanisms underlying foetal growth
      restriction and then tests strategies to improve growth and ameliorate many of
      the metabolic problems before the infant is born. The goal of our studies is to
      reduce the impact of foetal growth restriction at critical stages of development
      on the lifelong complications of IUGR offspring. CONCLUSION: Defining specific
      mechanisms that cause growth restriction in the foetus might identify specific
      nutrients and hormones that could be given to the mother to improve foetal growth
      and reduce metabolic complications, using strategies first tested in our IUGR
      animal model.

PMID- 27028696
TI  - Role of Automation/Technology in Day-to-Day Diabetes Care.

PMID- 27028698
TI  - A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone
      for the detection of preeclampsia/HELLP syndrome.
AB  - OBJECTIVE: The Elecsys((r)) immunoassay sFlt-1/PlGF ratio and the Triage((r))
      PlGF assay were compared (in a prospective, multicenter, case-control study) for
      diagnosis of preeclampsia/hemolysis, elevated liver enzymes, low platelets
      (HELLP) syndrome. METHODS: Women in European perinatal care centers with
      singleton pregnancies were enrolled: 178 cases had confirmed preeclampsia and 391
      controls had normal outcome. Patients in the preeclampsia/HELLP syndrome group
      were matched pairwise by gestational week to healthy controls (1:2). Maternal
      blood samples were analyzed using (a) fully automated Elecsys PlGF and Elecsys
      sFlt-1 immunoassays with two cutoffs (early-onset [<34 weeks] <=33, >=85; late
      onset [>=34 weeks] <=33, >=110), and (b) Triage PlGF immunoassay (single cutoff).
      Diagnostic performance and utility were assessed. RESULTS: Respectively, 83 and
      95 women had early-onset or late-onset preeclampsia/HELLP syndrome. The overall
      diagnostic performance of the Elecsys immunoassay sFlt-1/PlGF ratio (area under
      the curve [AUC] 0.941) was higher than for Triage PlGF (AUC 0.917). The Elecsys
      immunoassay sFlt-1/PlGF ratio sensitivity and specificity was: 94.0% (95%
      confidence interval [CI] 86.5-98.0) and 99.4% (95% CI: 96.8-99.9) for early-onset
      preeclampsia; and 89.5% (95% CI: 81.5-94.8) and 95.4% (95% CI: 91.7-97.8) for
      late-onset preeclampsia. The Triage assay sensitivity and specificity was: 96.4%
      (95% CI: 89.8-99.3) and 88.5% (95% CI: 82.8-92.8) (early-onset); and 90.5% (95%
      CI: 83-96) and 64.5% (95% CI: 57.8-70.9) (late onset). CONCLUSIONS: The fully
      automated Elecsys immunoassay sFlt-1/PlGF ratio provides improved diagnostic
      utility over the Triage PlGF assay with improved specificity for the clinical
      management of pregnant women with suspected preeclampsia/HELLP syndrome.

PMID- 27028699
TI  - Prader-Willi Syndrome, Management of Impulsivity, and Hyperphagia in an
      Adolescent.
AB  - The aim of this article is to review related literature on management of
      hyperphagia and impulsive behaviors in Prader-Willi syndrome (PWS) that includes
      either naltrexone or bupropion. In this article we also discuss a case of a 13
      year-old female with PWS struggling with some behavioral and psychiatric
      symptoms.

PMID- 27028700
TI  - The inter-arm systolic blood pressure difference and risk of cardiovascular
      mortality: A meta-analysis of cohort studies.
AB  - The inter-arm systolic blood pressure difference (SBPD) is recommended to be in
      relation to potential cardiovascular disease (CVD). Previous studies yielded
      controversial results about the association between an inter-arm SBPD >= 10 mmHg
      or >=15 mmHg and the risk of cardiovascular mortality. Therefore, we conducted
      this meta-analysis to investigate this association. We searched PubMed and Embase
      databases through December 31, 2014, and examined the references of retrieved
      articles to identify relevant cohort studies. We utilized Newcastle-Ottawa scale
      to assess the quality of included studies and calculated the summary risk
      estimates in a fixed/random-effect model. All data analyses were conducted using
      STATA version 11.0. A total of seven studies were identified. Compared with
      participants with an inter-arm SBPD < 10 mmHg, the pooled hazard ratio (HR) of
      CVD mortality of those with an inter-arm SBPD >= 10 mmHg was 1.58 (95% CI: 1.3
      1.93), and the pooled HR of cardiovascular mortality of participants with an
      inter-arm SBPD >= 15 mmHg versus those with an inter-arm SBPD < 15 mmHg was 1.88
      (95% CI: 1.33-2.66). The findings from the present meta-analysis indicated that
      the detection of an inter-arm SBPD may define a subpopulation at high risk of CVD
      events.

PMID- 27028701
TI  - Quality Health Care and Willingness to Pay for Health Insurance Retention: A
      Randomized Experiment in Kolkata Slums.
AB  - The low quality of health care in developing countries reduces the poor's
      incentives to use quality health services and their demand for health insurance.
      Using data from a field experiment in India, I show that randomly offering
      insurance policyholders a free preventive checkup with a qualified doctor has a
      twofold effect: receiving this additional benefit raises willingness to pay to
      renew health insurance by 53%, doubling the likelihood of hypothetical renewal;
      exposed individuals are 10 percentage points more likely to consult a qualified
      practitioner when ill after the checkup. Both effects are concentrated on poorer
      households. There is no effect on health knowledge and healthcare spending. This
      suggests that exposing insured households to quality preventive care can be a
      cost-effective way of raising the demand for quality health care and retaining
      policyholders in the insurance scheme. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27028702
TI  - Nutritional Epidemiology of Antenatal Smoking Cessation Among Japanese Women.
AB  - This study compared the nutritional status before pregnancy, as well as dietary
      profiles and biomarkers during first trimester, between never-smokers and
      antenatal quitters among Japanese women. One hundred fifty pregnant women (79
      never-smokers and 71 antenatal quitters) from two obstetrics and gynecology
      clinics were recruited in Japan. Subjects' prepregnancy nutritional status was
      indicated by their body mass index (BMI). In the first trimester, their dietary
      profiles were assessed by the Brief Diet-History Questionnaire (BDHQ) and
      pregnancy outcomes were screened by biomarker tests. Generalized linear
      regression was used to examine the differences of energy-adjusted dietary intakes
      and biomarker results between the two smoking groups, with adjustment of maternal
      age, BMI, gestation week, and parity. The results showed that antenatal quitters
      were more likely to have a prepregnancy underweight status than never-smokers.
      During the first trimester, antenatal quitters had significantly higher intakes
      of unsaturated fatty acids and antioxidants (vegetable lipids and isoflavone),
      and lower intakes of total cholesterol than never-smokers. Moreover, antenatal
      quitters had a significantly higher level of serum homocysteine (6.36 nmol/mL vs
      4.88 nmol/mL) than never-smokers. In conclusion, antenatal quitters are more
      likely to have a poor nutritional status before pregnancy than never-smokers.
      Quitting smoking before pregnancy and having a good nutritional profile during
      the trimester may not sufficiently reverse the adverse effects of former smoking
      behaviors on pregnancy outcomes. 

PMID- 27028703
TI  - Influenza vaccination uptake among Victorian healthcare workers: evaluating the
      success of a statewide program.
AB  - OBJECTIVE: Annual influenza vaccination is recommended for all Australian
      healthcare workers (HCWs). In 2014, a target vaccination uptake of 75% was set
      for Victorian healthcare facilities. This study aimed to determine the 2014
      uptake, describe trends over time and propose an enhanced reporting framework.
      METHODS: Annual data submitted to the Victorian Healthcare Associated Infection
      Surveillance System (VICNISS) regarding HCW influenza were evaluated for 2005
      2014. Faculty uptake - the number of vaccinations administered divided by total
      number of staff employed - was reported as a statewide aggregate and stratified
      by facility size (number of staff employed). RESULTS: In 2014, 78,885 HCWs were
      vaccinated across 93 healthcare facilities, corresponding to an overall uptake of
      72.2%. During 2005-2014, small facilities (<100 HCWs) generally reported highest
      uptake while larger facilities (>=800 HCWs) recorded lowest uptake. Larger
      facilities recorded the greatest increase (+13.9%) when 2013 and 2014 seasons
      were compared. For all healthcare facility size categories, the highest uptake
      was observed in 2014. CONCLUSION: Influenza vaccination uptake in HCWs has
      successfully been introduced as a performance indicator in Victorian healthcare
      facilities and a peak uptake was reported in 2014. Varied trends are evident when
      uptake is stratified by number of employed HCWs, providing a feasible and
      meaningful method for benchmarking.

PMID- 27028704
TI  - A Model of Excitotoxic Brain Injury in Larval Zebrafish: Potential Application
      for High-Throughput Drug Evaluation to Treat Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a leading cause of death and morbidity with no
      effective therapeutic treatments for secondary injury. Preclinical drug
      evaluation in rodent models of TBI is a lengthy process. In this regard, the
      zebrafish has numerous advantages to address the technical and time-dependent
      obstacles associated with drug evaluation. We developed a reproducible brain
      injury using glutamate excitoxicity in zebrafish larvae, a known initiator of
      delayed cell death in TBI. Glutamate challenge resulted in dose-dependent
      lethality over an 84-h observation period. We report significant decrease in
      locomotion (p < 0.0001) and mean velocity (p < 0.001) with 10 MUM glutamate
      application as measured through automated 96-well plate behavioral analysis.
      Application of the NMDA receptor antagonist MK-801 (400 nM) or the calpain
      inhibitor, MDL-28170 (20 MUM), resulted in significant recovery of locomotor
      function. A secA5-YFP transgenic line was used to visualize the localization of
      cell death due to glutamate exposure in vivo using confocal fluorescence
      microscopy. Our results indicate that zebrafish larvae exhibit responses to
      excitotoxic injury and pharmacotherapeutic intervention with pathophysiological
      relevance to mammalian excitotoxic brain injury. This system has potential to be
      applied as a high-throughput drug screening model to quickly identify candidate
      lead compounds for further evaluation.

PMID- 27028705
TI  - Use of Ambient Ionization High-Resolution Mass Spectrometry for the Kinetic
      Analysis of Organic Surface Reactions.
AB  - In contrast to homogeneous systems, studying the kinetics of organic reactions on
      solid surfaces remains a difficult task due to the limited availability of
      appropriate analysis techniques that are general, high-throughput, and capable of
      offering quantitative, structural surface information. Here, we demonstrate how
      direct analysis in real time mass spectrometry (DART-MS) complies with above
      considerations and can be used for determining interfacial kinetic parameters.
      The presented approach is based on the use of a MS tag that--in principle--allows
      application to other reactions. To show the potential of DART-MS, we selected the
      widely applied strain-promoted alkyne-azide cycloaddition (SPAAC) as a model
      reaction to elucidate the effects of the nanoenvironment on the interfacial
      reaction rate.

PMID- 27028706
TI  - Preoperative portal vein embolization for hepatocellular carcinoma: Consensus and
      controversy.
AB  - Thirty years have passed since the first report of portal vein embolization
      (PVE), and this procedure is widely adopted as a preoperative treatment procedure
      for patients with a small future liver remnant (FLR). PVE has been shown to be
      useful in patients with hepatocellular carcinoma (HCC) and chronic liver disease.
      However, special caution is needed when PVE is applied prior to subsequent major
      hepatic resection in cases with cirrhotic livers, and volumetric analysis of the
      liver segments in addition to evaluation of the liver functional reserve before
      PVE is mandatory in such cases. Advances in the embolic material and selection of
      the treatment approach, and combined use of PVE and transcatheter arterial
      embolization/chemoembolization have yielded improved outcomes after PVE and major
      hepatic resections. A novel procedure termed the associating liver partition and
      portal vein ligation for staged hepatectomy has been gaining attention because of
      the rapid hypertrophy of the FLR observed in patients undergoing this procedure,
      however, application of this technique in HCC patients requires special caution,
      as it has been shown to be associated with a high morbidity and mortality even in
      cases with essentially healthy livers. 

PMID- 27028707
TI  - Murine startle mutant Nmf11 affects the structural stability of the glycine
      receptor and increases deactivation.
AB  - KEY POINTS: Hyperekplexia or startle disease is a serious neurological condition
      affecting newborn children and usually involves dysfunctional glycinergic
      neurotransmission. Glycine receptors (GlyRs) are major mediators of inhibition in
      the spinal cord and brainstem. A missense mutation, replacing asparagine (N) with
      lysine (K), at position 46 in the GlyR alpha1 subunit induced hyperekplexia
      following a reduction in the potency of the transmitter glycine; this resulted
      from a rapid deactivation of the agonist current at mutant GlyRs. These effects
      of N46K were rescued by mutating a juxtaposed residue, N61 on binding Loop D,
      suggesting these two asparagines may interact. Asparagine 46 is considered to be
      important for the structural stability of the subunit interface and glycine
      binding site, and its mutation represents a new mechanism by which GlyR
      dysfunction induces startle disease. ABSTRACT: Dysfunctional glycinergic
      inhibitory transmission underlies the debilitating neurological condition,
      hyperekplexia, which is characterised by exaggerated startle reflexes, muscle
      hypertonia and apnoea. Here we investigated the N46K missense mutation in the
      GlyR alpha1 subunit gene found in the ethylnitrosourea (ENU) murine mutant,
      Nmf11, which causes reduced body size, evoked tremor, seizures, muscle stiffness,
      and morbidity by postnatal day 21. Introducing the N46K mutation into recombinant
      GlyR alpha1 homomeric receptors, expressed in HEK cells, reduced the potencies of
      glycine, beta-alanine and taurine by 9-, 6- and 3-fold respectively, and that of
      the competitive antagonist strychnine by 15-fold. Replacing N46 with hydrophobic,
      charged or polar residues revealed that the amide moiety of asparagine was
      crucial for GlyR activation. Co-mutating N61, located on a neighbouring beta loop
      to N46, rescued the wild-type phenotype depending on the amino acid charge.
      Single-channel recording identified that burst length for the N46K mutant was
      reduced and fast agonist application revealed faster glycine deactivation times
      for the N46K mutant compared with the WT receptor. Overall, these data are
      consistent with N46 ensuring correct alignment of the alpha1 subunit interface by
      interaction with juxtaposed residues to preserve the structural integrity of the
      glycine binding site. This represents a new mechanism by which GlyR dysfunction
      induces startle disease.

PMID- 27028708
TI  - Postcomparison of [(18) F]-fluorodeoxyglucose uptake in the brain after short
      term bright light exposure and no intervention.
AB  - OBJECTIVE: Bright light therapy is widely used as the treatment of choice for
      seasonal affective disorder. Nonetheless, our understanding of the mechanisms of
      bright light is limited and it is important to investigate the mechanisms. The
      purpose of this study is to examine the hypothesis that bright light exposure may
      increase [(18) F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or
      hippocampus which may be associated neurogenesis in the human brain. METHOD: A
      randomized controlled trial comparing 5-day bright light exposure + environmental
      light (bright light exposure group) with environmental light alone (no
      intervention group) was performed for 55 participants in a university hospital.
      The uptake of [(18) F]FDG in olfactory bulb and hippocampus using FDG positron
      emission tomography was compared between two groups. RESULTS: There was a
      significant increase of uptake in both right and left olfactory bulb for bright
      light exposure group vs. no intervention group. After adjustment of log
      transformed illuminance, there remained a significant increase of uptake in the
      right olfactory bulb. CONCLUSION: The present findings suggest a possibility that
      5-day bright light exposure may increase [(18) F]FDG in the right olfactory bulb
      of the human brain, suggesting a possibility of neurogenesis. Further studies are
      warranted to directly confirm this possibility.

PMID- 27028709
TI  - Association of Leptin with Body Pain in Women.
AB  - Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory
      adipokine. One of the effects of increased systemic leptin concentrations may be
      greater sensitivity to pain. We report the results of two studies examining the
      association between leptin and pain: a small pilot longitudinal study, followed
      by a large cross-sectional study. In Study 1, three women with physician
      diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as
      well as daily self-reported musculoskeletal pain. Daily fluctuations in serum
      leptin were positively associated with pain across all three participants (F
      (1,63) = 12.8, p < 0.001), with leptin predicting ~49% of the pain variance. In
      Study 2, the relationship between leptin and body pain was examined in a
      retrospective cross-sectional analysis of 5676 generally healthy postmenopausal
      women from the Women's Health Initiative. Leptin levels obtained from single
      blood draws were tested for a relationship with self-reported body pain. Body
      mass index (BMI) was also included as a predictor of pain. Both leptin and BMI
      were found to be independently associated with self-reported pain (p = 0.001 and
      p < 0.001, respectively), with higher leptin levels and greater BMI each being
      associated with greater pain. Leptin appears to be a predictor of body pain both
      within- and between-individuals and may be a driver of generalized pain states
      such as fibromyalgia.

PMID- 27028710
TI  - Predictive factors in patients undergoing endoscopic sinus surgery for
      odontogenic sinusitis.
AB  - BACKGROUND: Odontogenic sinusitis (OS) presents a therapeutic dilemma. Evidence
      is lacking whether dental treatment alone is sufficient or whether patients will
      eventually require endoscopic sinus surgery (ESS). Our aim was to identify
      predictors of OS patients undergoing ESS. METHODS: Retrospective review performed
      of OS patients (n = 43) analyzing multiple factors including age, sex, symptoms,
      prior dental procedures, treatment, diabetes, immunosuppression, smoking history,
      retained dental hardware, oral-antral fistula (OAF), and Lund-Mackay scores
      (LMSs). Descriptive statistics, Wilcoxon rank sum, and logistic regression
      analyses were performed. RESULTS: Common presenting symptoms included facial
      pressure, discolored nasal drainage, and foul smell/taste. Half of patients
      presented either after a recent dental procedure or with dental complaints. Forty
      eight percent required ESS after failing medical and dental therapy alone. Total
      LMS was significantly higher in the group undergoing ESS (8.3 vs 3.7; p =
      0.0003). Multivariate analysis showed 2 significant predictors of undergoing ESS:
      (1) OMC involvement (OR 37.3, p = 0.003) and prior dental procedure (OR 7.4, p =
      0.03). All patients with OAF or retained dental hardware required ESS.
      CONCLUSION: Forty-eight percent of patients who presented with OS underwent ESS
      for symptom control and prevention of complications. Patients who underwent ESS
      had significantly higher total LMS than those who did not. In multivariate
      analysis, prior dental procedures and OMC involvement significantly increased the
      likelihood of requiring ESS.

PMID- 27028714
TI  - The Baader-Meinhof phenomenon in ductal carcinoma in situ of the breast.

PMID- 27028716
TI  - Selective Sorption of Light Hydrocarbons on a Family of Metal-Organic Frameworks
      with Different Imidazolate Pillars.
AB  - Four isostructural pillared-layer metal-organic frameworks (as 1-ims series) are
      successfully synthesized via the charge-balance approach, where trigonal
      [Zn2(CO2)3] cluster-based cationic layers [Zn2(NH2-BTB)](+) (NH2-H3BTB = 1,3,5-(3
      benzoic acid) aniline) are connected by a series of 2-substituted imidazolates.
      The 1-ims supply a systematic platform to explore the adsorption of light
      hydrocarbons. Especially, 1-ims shows good adsorption selectivity of C3/C1 and
      C2/C1, and the selectivities of C3H8/CH4 are all over 100 at room temperature.
      These results demonstrate that introduction of functional group plays a key role
      on tuning the channel and pore size as well as improving the adsorption
      selectivity. 

PMID- 27028715
TI  - Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic
      mice.
AB  - It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk
      for fragility fractures, an effect that has been largely ascribed to decreased
      bone formation. However, the potential role of decreased angiogenesis as a factor
      in osteogenesis reduction has not been extensively studied. Furthermore, there is
      controversy surrounding the effect of T1D on bone resorption. This study
      characterized bone microstructure, bone strength, and bone turnover of
      streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of
      angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate
      that T1D deteriorated trabecular microarchitecture and led to reduced bone
      strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface
      (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation
      rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown
      by a reduced number of blood vessels in the femur and decreased expression of
      platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia
      inducible factor-1alpha, and vascular endothelial growth factor was observed. On
      the other hand, reduced bone resorption, an effect that could lead to impaired
      osteogenesis, was demonstrated by lower osteoclast number/BS and decreased
      tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number
      of osteoblasts and decreased expression of receptor activator for nuclear factor
      kappaB ligand could be responsible for compromised bone resorption in T1D mice.
      In conclusion, T1D mice display reduced bone formation and bone resorption,
      suggesting decreased bone turnover. Furthermore, this study points to impairments
      in angiogenesis as a pivotal cause of decreased bone formation.

PMID- 27028717
TI  - An investigation of the interactions of Eu3+ and Am3+ with uranyl minerals:
      implications for the storage of spent nuclear fuel.
AB  - The reaction of a number of uranyl minerals of the (oxy)hydroxide, phosphate and
      carbonate types with Eu(iii), as a surrogate for Am(iii), have been investigated.
      A photoluminescence study shows that Eu(iii) can interact with the uranyl
      minerals Ca[(UO2)6(O)4(OH)6].8H2O (becquerelite) and A[UO2(CO3)3].xH2O (A/x =
      K3Na/1, grimselite; CaNa2/6, andersonite; and Ca2/11, liebigite). For the
      minerals [(UO2)8(O)2(OH)12].12H2O (schoepite), K2[(UO2)6(O)4(OH)6].7H2O
      (compreignacite), A[(UO2)2(PO4)2].8H2O (A = Ca, meta-autunite; Cu, meta
      torbernite) and Cu[(UO2)2(SiO3OH)2].6H2O (cuprosklodowskite) no Eu(iii) emission
      was observed, indicating no incorporation into, or sorption onto the structure.
      In the examples with Eu(3+) incorporation, sensitized emission is seen and the
      lifetimes, hydration numbers and quantum yields have been determined. Time
      Resolved Laser Induced Fluroescence Spectroscpoy (TRLFS) at 10 K have also been
      measured and the resolution enhancements at these temperatures allow further
      information to be derived on the sites of Eu(iii) incorporation. Infrared and
      Raman spectra are recorded, and SEM analysis show significant morphology changes
      and the substitution of particularly Ca(2+) by Eu(3+) ions. Therefore, Eu(3+) can
      substitute Ca(2+) in the interlayers of becquerelite and liebigite and in the
      structure of andersonite, whilst in grimselite only sodium is exchanged. These
      results have guided an investigation into the reactions with (241)Am on a tracer
      scale and results from gamma-spectrometry show that becquerelite, andersonite,
      grimselite, liebigite and compreignacite can include americium in the structure.
      Shifts in the U[double bond, length as m-dash]O and C-O Raman active bands are
      similar to that observed in the Eu(iii) analogues and Am(iii) photoluminescence
      measurements are also reported on these phases; the Am(3+) ion quenches the
      emission from the uranyl ion.

PMID- 27028718
TI  - Enhancement of Lytic Activity by Leptin Is Independent From Lipid Rafts in Murine
      Primary Splenocytes.
AB  - Leptin, a pleiotropic adipokine, is known as a regulator of food intake, but it
      is also involved in inflammation, immunity, cell proliferation, and survival.
      Leptin receptor is integrated inside cholesterol-rich microdomains called lipid
      rafts, which, if disrupted or destroyed, could lead to a perturbation of lytic
      mechanism. Previous studies also reported that leptin could induce membrane
      remodeling. In this context, we studied the effect of membrane remodeling in
      lytic activity modulation induced by leptin. Thus, primary mouse splenocytes were
      incubated with methyl-beta-cyclodextrin (beta-MCD), a lipid rafts disrupting
      agent, cholesterol, a major component of cell membranes, or ursodeoxycholic acid
      (UDCA), a membrane stabilizer agent for 1 h. These treatments were followed by
      splenocyte incubation with leptin (absence, 10 and 100 ng/ml). Unlike beta-MCD or
      cholesterol, UDCA was able to block leptin lytic induction. This result suggests
      that leptin increased the lytic activity of primary spleen cells against syngenic
      EO771 mammary cancer cells independently from lipid rafts but may involve
      membrane fluidity. Furthermore, natural killer cells were shown to be involved in
      the splenocyte lytic activity. To our knowledge it is the first publication in
      primary culture that provides the link between leptin lytic modulation and
      membrane remodeling. J. Cell. Physiol. 232: 101-109, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27028719
TI  - Effect of exercise intervention on the perceptual-motor skills in adolescents
      with autism.
AB  - BACKGROUND: Motor skill impairment has been reported in many studies of autistic
      adolescents. The aim of this study was to examine the effect of selected physical
      exercise on Perceptual-motor skills in adolescents with autism. METHODS: Twenty
      adolescents with autism that were under special education in Tehran based on
      their Childhood Autism Rating Scale (CARS) scores and level of abilities were
      selected. Measurement tool was Bruininks-Oseretsky Test of Motor Proficiency
      (BOTMP). Selected group motor program in this study includes motor activities,
      games and sports for adolescents that were performed for 10 weeks. RESULTS:
      Results showed that selected physical exercise training has significant effects
      on all of the variables (P<0.001) except the speed of running and agility
      (P=0.61), bilateral coordination (P=0.12) and response speed (P=0.42).
      CONCLUSIONS: It seems that miscellaneous physical exercise programs which include
      ball games, delightful play and targeted play can improve perceptual-motor skills
      in adolescents with autism.

PMID- 27028720
TI  - Range of motion of body segments is larger during the maximal instep kick than
      during the submaximal kick in experienced football players.
AB  - BACKGROUND: Football players with groin injury refrain from maximal kicking.
      Previous groin injury is related to decreased hip range of motion (ROM).
      Information on ROM differences between maximal and submaximal kicking within
      players is lacking. The first aim of this study is to quantify ROM of body
      segments during the maximal (MaxK) and submaximal (SubK) instep kick at four key
      points. The second aim is to study ROM differences of tension arc and movement
      trajectories between MaxK and SubK. METHODS: Maximal (100% ball speed) and
      submaximal (70% ball speed) instep kicks from 15 experienced football players
      were registered with motion capture. ROM of hip, spine, pelvis and knee segments
      were determined at four key points. Differences in segmental ROM for the tension
      arc and movement trajectories between MaxK and SubK were studied. Effect sizes
      (ES) were calculated. RESULTS: Ball speed was 98.8+/-9.0 km/h for MaxK and 69.5+/
      7.1 km/h for SubK. Three key points timed similarly (P<0.05) for MaxK and SubK.
      MaxK shows increased ROM for all segments (P<0.05) but not for hip flexion. MaxK
      results in enlargement of tension arc and movement trajectories. Spine flexion
      (ES=3.2) and pelvis posterior tilt (ES=2.2) show the greatest relative increase.
      CONCLUSIONS: Maximal kicking shows larger segmental ROM than submaximal kicking.
      Enlargement of tension arc and movement trajectories relate to increased
      segmental velocity, according to biomechanical concepts. Central body actions
      play an important role in kicking. This information can be used to further
      identify kicking strategies in athletes with injury.

PMID- 27028721
TI  - Using Bayesian analysis in repeated preclinical in vivo studies for a more
      effective use of animals.
AB  - Whilst innovative Bayesian approaches are increasingly used in clinical studies,
      in the preclinical area Bayesian methods appear to be rarely used in the
      reporting of pharmacology data. This is particularly surprising in the context of
      regularly repeated in vivo studies where there is a considerable amount of data
      from historical control groups, which has potential value. This paper describes
      our experience with introducing Bayesian analysis for such studies using a
      Bayesian meta-analytic predictive approach. This leads naturally either to an
      informative prior for a control group as part of a full Bayesian analysis of the
      next study or using a predictive distribution to replace a control group
      entirely. We use quality control charts to illustrate study-to-study variation to
      the scientists and describe informative priors in terms of their approximate
      effective numbers of animals. We describe two case studies of animal models: the
      lipopolysaccharide-induced cytokine release model used in inflammation and the
      novel object recognition model used to screen cognitive enhancers, both of which
      show the advantage of a Bayesian approach over the standard frequentist analysis.
      We conclude that using Bayesian methods in stable repeated in vivo studies can
      result in a more effective use of animals, either by reducing the total number of
      animals used or by increasing the precision of key treatment differences. This
      will lead to clearer results and supports the "3Rs initiative" to Refine, Reduce
      and Replace animals in research. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27028722
TI  - How action researchers use anxiety to facilitate change in health care.
AB  - AIM: The aim of this paper is to report on the role of an action researcher in a
      study investigating the change process in a health service context where a new
      assessment clinic was developed to manage the excessive waiting list for that
      service. BACKGROUND: For effective organisational change in health, there is a
      suggestion that change agents need to be emotionally intelligent; recognising the
      emotional state of individuals, reconciling that with the organisational drivers
      and making an assessment of readiness for organisational change. Anxiety features
      throughout this literature and there is a suggestion that being aware of anxiety
      and managing anxiety is within the emotionally intelligent change agent's
      repertoire, but there is a gap in the literature that explains this relationship
      in detail. METHODS: Data were generated to investigate the discrete nature of the
      role of the action researcher during this organisational change that spanned two
      years, through three methods: participant observations in the field captured in
      field notes (n = 72); observations of team meetings that had been recorded and
      transcribed (n = 13); interviews with key informants pre- and postintervention (n
      = 14); a reflexive diary one document of 8920 words (n = 1). FINDINGS: The data
      illuminating the interaction between the action researcher and participants were
      synthesised into two broad themes: how the action researcher introduced anxiety
      into the system; how the action researcher facilitated the participants to
      tolerate change anxiety. DISCUSSION/RELEVANCE TO CLINICAL PRACTICE: The findings
      from this study can be applied in clinical practice where change in practice is
      planned. Part of the requirement of a change agent in the NHS might be to be
      sufficiently emotionally literate to understand anxiety in the participant system
      and manage it to effect change.

PMID- 27028723
TI  - Expanding Biosensing Abilities through Computer-Aided Design of Metabolic
      Pathways.
AB  - Detection of chemical signals is critical for cells in nature as well as in
      synthetic biology, where they serve as inputs for designer circuits. Important
      progress has been made in the design of signal processing circuits triggering
      complex biological behaviors, but the range of small molecules recognized by
      sensors as inputs is limited. The ability to detect new molecules will increase
      the number of synthetic biology applications, but direct engineering of tailor
      made sensors takes time. Here we describe a way to immediately expand the range
      of biologically detectable molecules by systematically designing metabolic
      pathways that transform nondetectable molecules into molecules for which sensors
      already exist. We leveraged computer-aided design to predict such sensing
      enabling metabolic pathways, and we built several new whole-cell biosensors for
      molecules such as cocaine, parathion, hippuric acid, and nitroglycerin.

PMID- 27028724
TI  - Fast production of microfluidic devices by CO2 laser engraving of wax-coated
      glass slides.
AB  - Glass is one of the most convenient materials for the development of microfluidic
      devices. However, most fabrication protocols require long processing times and
      expensive facilities. As a convenient alternative, polymeric materials have been
      extensively used due their lower cost and versatility. Although CO2 laser
      ablation has been used for fast prototyping on polymeric materials, it cannot be
      applied to glass devices because the local heating causes thermal stress and
      results in extensive cracking. A few papers have shown the ablation of channels
      or thin holes (used as reservoirs) on glass but the process is still far away
      from yielding functional glass microfluidic devices. To address these
      shortcomings, this communication describes a simple method to engrave glass-based
      capillary electrophoresis devices using standard (1 mm-thick) microscope glass
      slides. The process uses a sacrificial layer of wax as heat sink and enables the
      development of both channels (with semicircular shape) and pass-through
      reservoirs. Although microscope images showed some small cracks around the
      channels (that became irrelevant after sealing the engraved glass layer to PDMS)
      the proposed strategy is a leap forward in the application of the technology to
      glass. In order to demonstrate the capabilities of the approach, the separation
      of dopamine, catechol and uric acid was accomplished in less than 100 s.

PMID- 27028725
TI  - Susceptibility of porcine endogenous retrovirus to anti-retroviral inhibitors.
AB  - BACKGROUND: Porcine endogenous retrovirus (PERV) is an endogenous retrovirus that
      poses a risk of iatrogenic transmission in the context of pig-to-human
      xenotransplantation. The lack of a means to control PERV infection in the context
      of pig-to-human xenotransplantation is a major concern in the field. In this
      study, we set out to evaluate the ability of currently licensed anti-HIV drugs,
      and other types of anti-retroviral compounds, to inhibit PERV infection in vitro.
      METHODS: We used target cells stably expressing one of the known PERV viral
      receptors, an infectious molecular clone, PERV-A 14/220, and at least one drug
      from each class of anti-retroviral inhibitors as well as off-label drugs shown to
      have anti-viral activities. The susceptibility of PERV-A 14/220 LacZ to the anti
      retroviral drugs was determined from infected cells by histochemical staining.
      RESULTS: We extend the results of previous studies by showing that, in addition
      to raltegravir, dolutegravir is found to have a potent inhibitory activity
      against PERV replication (IC50 8.634 +/-0.336 and IC50 3.06 +/- 0.844 nM,
      respectively). The anti-HIV drug zidovudine (AZT) showed considerable anti-PERV
      activity with IC50 of 1.923 +/-0.691 MUM as well. CONCLUSIONS: The study results
      indicate that some of the licensed anti-retroviral drugs may be useful for
      controlling PERV infection. However, the efficacy at nanomolar concentrations put
      forward integrase inhibitors as a drug that has the potential to be useful in the
      event that xenotransplantation recipients have evidence of PERV transmission and
      replication.

PMID- 27028726
TI  - Epidermoid cyst of the testis: An atypical sonographic appearance.
AB  - Epidermoid cysts are rare. They represent the most common benign tumor of the
      testis. The sonographic appearances of testicular epidermoid cysts usually
      include avascular, mostly lamellated, heterogeneous internal echotexture, with
      hypoechoic and hyperechoic concentric rings, accounting for the typical onion
      ring appearance. On MRI, epidermoid cysts show a low-signal-intensity center,
      with internal concentric rings of alternating high- and low-signal intensity on
      T2-weighted images, which correlates with the onion-ring appearance. We report a
      patient with testicular epidermoid cyst with atypical ultrasound and MRI
      appearances that led to the erroneous initial diagnosis of "burned-out" tumor.
      (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:448-451, 2016. 

PMID- 27028727
TI  - A Comparison Among 5 Methods for the Clinical Diagnosis of Fetal Alcohol Spectrum
      Disorders.
AB  - BACKGROUND: Despite the prevalence of fetal alcohol spectrum disorders (FASD) and
      the importance of accurate identification of patients, clinical diagnosis may not
      be consistent across sites due to the heterogeneous nature of FASD and the
      characteristics of different diagnostic systems used. Here, we compare 5 systems
      designed to operationalize criteria recommended for the diagnosis of effects of
      prenatal alcohol exposure (PAE). We determined the extent of consistency among
      them as well as factors that may reduce intersystem reliability. Compared are:
      Emory Clinic, Seattle 4-Digit System (Diagnostic Guidelines for Fetal Alcohol
      Spectrum Disorders: The 4-Digit Diagnostic Code, Seattle, WA, University
      Publication Services, 2004), Centers for Disease Control and Prevention (Fetal
      Alcohol Syndrome: Guidelines for Referral and Diagnosis, Department of Health and
      Human Services, Centers for Disease Control and Prevention, Atlanta, GA, 2004),
      Canadian Guidelines (CMAJ, 172, 2005, S1), and the Hoyme Modifications
      (Pediatrics, 115, 2005, 39). METHODS: Subjects were 1,581 consecutively
      registered patients applying for evaluation at a university-based clinic treating
      alcohol and drug-exposed children. Records of the multidisciplinary evaluation
      (pediatric, social, psychological) were abstracted. Diagnostic criteria for all 5
      systems were applied, and patients were diagnosed according to each of the
      systems. We compared results using Cohen's Kappa to evaluate the extent of
      agreement. RESULTS: Percent of individuals diagnosed with FASD ranged from 4.74%
      (CDC) to 59.58% (Hoyme). Examination using Cohen's Kappa found modest agreement
      among systems, particularly when individual diagnoses, Fetal Alcohol Syndrome
      (FAS), partial FAS (pFAS), and Alcohol-Related Neurodevelopmental Disorder (ARND)
      were used. Examination of diagnostic criteria found almost perfect agreement on
      growth (weight; height), with limited overlap for physical features (palpebral
      fissures, hypoplastic philtrum, upper vermillion) and for neurobehavioral
      outcomes. Child's race and age influenced agreement among systems, with African
      American and older children more frequently diagnosed. CONCLUSIONS: Results
      suggest problems in convergent validity among these systems, as demonstrated by a
      lack of reliability in diagnosis. Absence of an external standard makes it
      impossible to determine whether any system is more accurate, but outcomes do
      suggest areas for future research that may refine diagnosis.

PMID- 27028728
TI  - Standardising Home Range Studies for Improved Management of the Critically
      Endangered Black Rhinoceros.
AB  - Comparisons of recent estimations of home range sizes for the critically
      endangered black rhinoceros in Hluhluwe-iMfolozi Park (HiP), South Africa, with
      historical estimates led reports of a substantial (54%) increase, attributed to
      over-stocking and habitat deterioration that has far-reaching implications for
      rhino conservation. Other reports, however, suggest the increase is more likely
      an artefact caused by applying various home range estimators to non-standardised
      datasets. We collected 1939 locations of 25 black rhino over six years (2004
      2009) to estimate annual home ranges and evaluate the hypothesis that they have
      increased in size. A minimum of 30 and 25 locations were required for accurate
      95% MCP estimation of home range of adult rhinos, during the dry and wet seasons
      respectively. Forty and 55 locations were required for adult female and male
      annual MCP home ranges, respectively, and 30 locations were necessary for
      estimating 90% bivariate kernel home ranges accurately. Average annual 95%
      bivariate kernel home ranges were 20.4 +/- 1.2 km(2), 53 +/- 1.9% larger than 95%
      MCP ranges (9.8 km(2) +/- 0.9). When home range techniques used during the late
      1960s in HiP were applied to our dataset, estimates were similar, indicating that
      ranges have not changed substantially in 50 years. Inaccurate, non-standardised,
      home range estimates and their comparison have the potential to mislead black
      rhino population management. We recommend that more care be taken to collect
      adequate numbers of rhino locations within standardized time periods (i.e.,
      season or year) and that the comparison of home ranges estimated using dissimilar
      procedures be avoided. Home range studies of black rhino have been data deficient
      and procedurally inconsistent. Standardisation of methods is required.

PMID- 27028729
TI  - Superior Sodium Storage in 3D Interconnected Nitrogen and Oxygen Dual-Doped
      Carbon Network.
AB  - Carbonaceous materials have attracted immense interest as anode materials for Na
      ion batteries (NIBs) because of their good chemical, thermal stabilities, as well
      as high Na-storage capacity. However, the carbonaceous materials as anodes for
      NIBs still suffer from the lower rate capability and poor cycle life. An N,O-dual
      doped carbon (denoted as NOC) network is designed and synthesized, which is
      greatly favorable for sodium storage. It exhibits high specific capacity and
      ultralong cycling stability, delivering a capacity of 545 mAh g(-1) at 100 mA g(
      1) after 100 cycles and retaining a capacity of 240 mAh g(-1) at 2 A g(-1) after
      2000 cycles. The NOC composite with 3D well-defined porosity and N,O-dual doped
      induces active sites, contributing to the enhanced sodium storage. In addition,
      the NOC is synthesized through a facile solution process, which can be easily
      extended to the preparation of many other N,O-dual doped carbonaceous materials
      for wide applications in catalysis, energy storage, and solar cells.

PMID- 27028730
TI  - Year in review 2015: Asthma and chronic obstructive pulmonary disease.

PMID- 27028731
TI  - Coho Salmon (Oncorhynchus kisutch) Prefer and Are Less Aggressive in Darker
      Environments.
AB  - Fish are capable of excellent vision and can be profoundly influenced by the
      visual properties of their environment. Ambient colours have been found to affect
      growth, survival, aggression and reproduction, but the effect of background
      darkness (i.e., the darkness vs. lightness of the background) on preference and
      aggression has not been evaluated systematically. One-hundred Coho salmon
      (Oncorhynchus kisutch), a species that is increasing in popularity in
      aquaculture, were randomly assigned to 10 tanks. Using a Latin-square design,
      every tank was bisected to allow fish in each tank to choose between all the
      following colour choices (8 choices in total): black vs. white, light grey, dark
      grey, and a mixed dark grey/black pattern, as well as industry-standard blue vs.
      white, light grey, dark grey, and black. Fish showed a strong preference for
      black backgrounds over all other options (p < 0.01). Across tests, preference
      strength increased with background darkness (p < 0.0001). Moreover, having darker
      backgrounds in the environment resulted in less aggressive behaviour throughout
      the tank (p < 0.0001). These results provide the first evidence that darker tanks
      are preferred by and decrease aggression in salmonids, which points to the
      welfare benefits of housing farmed salmon in enclosures containing dark
      backgrounds. 

PMID- 27028732
TI  - Recommended European Society of Parenteral and Enteral Nutrition protein and
      energy intakes and weight loss in patients with head and neck cancer.
AB  - BACKGROUND: Information regarding attenuation of weight loss in patients with
      head and neck cancer consuming energy and protein intakes at levels recommended
      by the European Society of Parenteral and Enteral Nutrition (ESPEN) is limited.
      METHODS: Newly diagnosed patients with head and neck cancer (n = 38) consuming
      food orally had weight and 3-day diet records prospectively collected at
      baseline, the end of treatment, and at the 2.5-month follow-up. Weight loss of
      patients consuming the ESPEN recommendations of >=30 kcal/kg/d energy and 1.2
      g/kg/d protein versus those consuming less were compared. Weight loss of oral
      nutrition supplement consumers versus oral nutrition supplement nonconsumers was
      also compared. RESULTS: Despite >=30 kcal/kg/d intakes at posttreatment and
      follow-up, mean weight loss was 10.3% from baseline to posttreatment, and 4.0%
      from posttreatment to follow-up. At posttreatment, oral nutrition supplement
      consumers with intakes >=30 kcal/kg/d lost twice as much weight as nonconsumers
      with intakes of >=30 kcal/kg/d (p = .001). CONCLUSION: Current ESPEN
      recommendations may not attenuate weight loss in patients with head and neck
      cancer, especially those consuming oral nutrition supplements. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 38:1248-1257, 2016.

PMID- 27028733
TI  - Incident reporting to BfArM - regulatory framework, results and challenges.
AB  - Medical devices are manifold and one of the most innovative fields of technology.
      As technologies advance, former limits cease to exist and complex devices become
      reality. Medical devices represent a very dynamic field with high economic
      relevance. The manufacturer of a medical device is obliged to minimize product
      related risks as well as to demonstrate compliance with the so-called "essential
      requirements" regarding safety and performance before placing the device on the
      market. Any critical incident in relation to the application of a medical device
      has to be reported to the competent authority for risk assessment, which in
      Germany is either the Federal Institute for Drugs and Medical Devices (BfArM) or
      the Paul Ehrlich Institute (PEI) depending on the type of device. In this
      article, the German regulatory framework for medical devices and the resulting
      tasks for BfArM are described as well as the topics of its recently installed
      research and development group on prospective risk identification and application
      safety for medical devices. Results of failure mode and root cause analyses of
      incident data are presented as well as further data on cases with the result
      "root-cause analysis not possible". Finally an outlook is given on future
      challenges regarding risk assessment for medical devices. 

PMID- 27028734
TI  - Monitoring multiple myeloma patients treated with daratumumab: teasing out
      monoclonal antibody interference.
AB  - BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As
      immunoglobulins, monoclonal antibodies have the potential to be identified by
      serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE).
      Therapeutic antibody interference with standard clinical SPE and IFE can confound
      the use of these tests for response assessment in clinical trials and disease
      monitoring. METHODS: To discriminate between endogenous myeloma protein and
      daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay
      (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether
      anti-daratumumab bound to and shifted the migration pattern of daratumumab, it
      was spiked into daratumumab-containing serum and resolved by IFE/SPE. The
      presence (DIRA positive) or absence (DIRA negative) of residual M-protein in
      daratumumab-treated patient samples was evaluated using predetermined assessment
      criteria. DIRA was evaluated for specificity, limit of sensitivity, and
      reproducibility. RESULTS: In all of the tested samples, DIRA distinguished
      between daratumumab and residual M-protein in commercial serum samples spiked
      with daratumumab and in daratumumab-treated patient samples. The DIRA limit of
      sensitivity was 0.2 g/L daratumumab, using spiking experiments. Results from DIRA
      were reproducible over multiple days, operators, and assays. The anti-daratumumab
      antibody was highly specific for daratumumab and did not shift endogenous M
      protein. CONCLUSIONS: As the treatment of myeloma evolves to incorporate novel
      monoclonal antibodies, additional solutions will be needed for clinical
      monitoring of patient responses to therapeutic regimens. In the interim, assays
      such as DIRA can inform clinical outcomes by distinguishing daratumumab from
      endogenous M-protein by IFE.

PMID- 27028735
TI  - Verification of the harmonization of human epididymis protein 4 assays.
AB  - BACKGROUND: Serum human epididymis protein 4 (HE4) has gained relevance as an
      ovarian cancer (OC) biomarker and new automated methods have replaced the first
      released manual EIA by tracing results to it. We verified agreement and bias of
      automated methods vs. EIA as well as possible effects on patients' management.
      METHODS: One hundred and fifteen serum samples were measured by Abbott Architect
      i2000, Fujirebio Lumipulse G1200, Roche Modular E170, and Fujirebio EIA. Passing
      Bablok regression was used to compare automated assays to EIA and agreement
      between methods was estimated by Lin's concordance correlation coefficient (CCC).
      The bias vs. EIA was estimated and compared to specifications derived from HE4
      biological variation. RESULTS: Median (25th-75th percentiles) HE4 concentrations
      (pmol/L) were 84.5 (60.1-148.8) for EIA, 82.7 (50.3-153.9) for Abbott, 89.1 (55.2
      154.9) for Roche, and 112.2 (67.8-194.2) for Fujirebio. Estimated regressions and
      agreements (95% confidence interval) were: Abbott=1.01(0.98-1.03) EIA-4.8(-7.5/
      2.6), CCC=0.99(0.99-1.00); Roche=0.91(0.89-0.93) EIA+5.7(4.2/8.0), CCC=0.98(0.98
      0.99); Fujirebio=1.20(1.17-1.24) EIA+ 2.4(-0.6/4.9), CCC=0.97(0.96-0.98). The
      average bias vs. EIA resulted within the desirable goal for Abbott [-3.3% (-6.1/
      0.5)] and Roche [-0.2% (-3.0/2.5)]. However, while for Abbott the bias was
      constant and acceptable along the measurement concentration range, Roche bias
      increased up to -28% for HE4 values >250 pmol/L. Lumipulse showed a markedly
      positive bias [25.3% (21.8/28.8)]. CONCLUSIONS: Abbott and Roche assays exhibited
      a good comparability in the range of HE4 values around the previously recommended
      140 pmol/L cut-off. For patient monitoring, however, the assay used for
      determining serial HE4 must not be changed as results from different systems in
      lower and higher concentration ranges can markedly differ.

PMID- 27028736
TI  - Distribution of antiphospholipid antibodies in a large population-based German
      cohort.
AB  - BACKGROUND: Antiphospholipid syndrome (APS) is the most common acquired
      thrombophilia. Diagnosis is based on clinical criteria and the presence of
      antiphospholipid antibodies (aPLs) above the 99th percentile of a reference
      group. Data on the distribution of aPL in the population are limited. The
      distribution of aPL including diagnostic cutoffs should be determined in a
      population-based cohort. METHODS: The Gutenberg Health Study (GHS) is a
      population-based cohort aged 35-74 years. We determined the presence of
      antibodies against cardiolipin (aCL, IgG, and IgM), beta2-glycoprotein I (anti
      beta2GPI, IgG, and IgM), and domain 1 of beta2-glycoprotein I (anti-domain 1,
      IgG) in a sample of 4979 participants. RESULTS: aPL titers were similar in the
      whole sample and in an apparently healthy subgroup of 1049 individuals. There was
      a strong age-dependent increase of both aCL and anti-beta2GPI IgM, while aPL IgG
      titers were stable or tended to decrease with age. A relevant decrease was
      observed for aCL IgG in women and anti-domain 1 IgG in both sexes. There was no
      association of aPL titers with a history of venous thromboembolism (VTE).
      CONCLUSIONS: Our data show that for IgM aPL, age-dependent reference ranges
      should be used. In fact, the controversy regarding the clinical utility of IgM
      aPL might be related to the use of inappropriate reference ranges among other
      causes. In our population, aPLs were not associated with a history of VTE.

PMID- 27028737
TI  - Impact of under-filled blood collection tubes containing K2EDTA and K3EDTA as
      anticoagulants on automated complete blood count (CBC) testing.

PMID- 27028740
TI  - Counseling Older Adults About Cognitive Decline.

PMID- 27028741
TI  - Stress and Parents of Children with Autism: A Review of Literature.
AB  - The purpose of this review is twofold. The first is to synthesize factors that
      impact parents' experiences of caring for a child with autism spectrum disorder
      (ASD); the second is to identify factors that impact parental stress and parental
      decision-making to use autism services or not. Parents of children with ASD score
      higher on levels of stress than other groups of parents. The daily challenges of
      caring for the child are endless and effect all aspects of the child's care as
      well as the parent's mental health and ability to manage the needs of the child
      and family. Understanding more about the challenges parents face will provide
      direction for research, intervention development, and practice. Accordingly, a
      search was conducted using CINAHL and Medline. Inclusion criteria included
      articles available in full text, published in English, and focused on children
      with ASD distinct from other diagnoses, as well as parental experiences of caring
      for a child with ASD. Articles (N = 132) that met the inclusion criteria were
      summarized. Challenging aspects of the child's diagnosis and care are discussed,
      as well as the factors that impact parental stress and decision-making to use
      autism services. Recommendations for research and practice include interventional
      development related to early diagnosis, disparity, access to care, parental
      decision-making to use autism services, and parental stress management. 

PMID- 27028742
TI  - Kindness and Its Relevance to Everyday Life: Some Considerations for Mental
      Health Nurses.

PMID- 27028744
TI  - Thermodynamic Study of the Role of Interface Curvature on Multicomponent Vapor
      Liquid Phase Equilibrium.
AB  - The effect of interface curvature on phase equilibrium has been much more studied
      for single-component than multicomponent systems. We isolate the effect of
      curvature on multicomponent vapor-liquid equilibrium (VLE) phase envelopes and
      phase composition diagrams using the ideal system methanol/ethanol and the
      nonideal system ethanol/water as illustrative examples. An important finding is
      how nanoscale interface curvature shifts the azeotrope (equal volatility point)
      of nonideal systems. Understanding of the effect of curvature on VLE can be
      exploited in future nanoscale prediction and design. 

PMID- 27028743
TI  - alpha1-Syntrophin Variant Identified in Drug-Induced Long QT Syndrome Increases
      Late Sodium Current.
AB  - Drug-induced long-QT syndrome (diLQTS) is often due to drug block of IKr,
      especially in genetically susceptible patients with subclinical mutations in the
      IKr-encoding KCHN2. Few variants in the cardiac NaV1.5 Na+ channel complex have
      been associated with diLQTS. We tested whether a novel SNTA1 (alpha1-syntrophin)
      variant (p.E409Q) found in a patient with diLQTS increases late sodium current
      (INa-L), thereby providing a disease mechanism. Electrophysiological studies were
      performed in HEK293T cells co-expressing human NaV1.5/nNOS/PMCA4b with either
      wild type (WT) or SNTA1 variants (A390V-previously reported in congenital LQTS;
      and E409Q); and in adult rat ventricular cardiomyocytes infected with SNTA1
      expressing adenoviruses (WT or one of the two SNTA1 variants). In HEK293T cells
      and in cardiomyocytes, there was no significant difference in the peak INa
      densities among the SNTA1 WT and variants. However, both variants increased INa-L
      (% of peak current) in HEK293T cells (0.58 +/- 0.10 in WT vs. 0.90 +/- 0.11 in
      A390V, p = 0.048; vs. 0.88 +/- 0.07 in E409Q, p = 0.023). In cardiomyocytes, INa
      L was significantly increased by E409Q, but not by A390V compared to WT (0.49 +/-
      0.14 in WT vs.0.94 +/- 0.23 in A390V, p = 0.099; vs. 1.12 +/- 0.24 in E409Q, p =
      0.019). We demonstrated that a novel SNTA1 variant is likely causative for diLQTS
      by augmenting INa-L. These data suggest that variants within the NaV1.5
      interacting alpha1-syntrophin are a potential mechanism for diLQTS, thereby
      expanding the concept that variants within congenital LQTS loci can cause diLQTS.

PMID- 27028745
TI  - Preoperative Oral Administration of Kikyo-To, a Kampo Medicine, Alleviates
      Postoperative Sore Throat: A Prospective, Double-Blind, Randomized Study.
AB  - OBJECTIVES: This study aimed to determine the efficacy of Kikyo-To (KKT), a Kampo
      medicine, in treating postoperative sore throat and nausea. DESIGN: This
      randomized, controlled, double-blind study was conducted among two groups of
      women who were scheduled to undergo benign surgery under general anesthesia. All
      patients had a physical status of 1 (normal, healthy patient) or 2 (patient with
      a mild systemic disease), according to the American Society of Anesthesiologists
      criteria. Patients were randomly assigned to the KKT group or the placebo
      (control) group. INTERVENTION: Before surgery, the KKT group received KKT (5.0 g)
      mixed with jelly, while the placebo group received only jelly. Patients and the
      evaluator were blinded to the treatment status. OUTCOME MEASURES: At 0, 3, and 24
      hours after anesthesia recovery, an investigator (also blinded to the treatment
      status) recorded the incidence and severity (using the Numeric Rating Scale
      [NRS]) of sore throat and nausea. RESULTS: The incidence of sore throat was
      significantly lower in the KKT group than in the control group immediately after
      surgery (p < 0.05). The severity of sore throat on the NRS was significantly
      lower in the KKT group than in the control group immediately and 3 hours after
      surgery (p < 0.05). In contrast, the incidence and severity of nausea did not
      differ significantly between the two groups. CONCLUSIONS: KKT administration
      before general anesthesia did not alleviate postoperative nausea but effectively
      decreased the incidence and severity of postoperative sore throat in women
      undergoing benign surgery.

PMID- 27028747
TI  - Technological change and sexual disorder.

PMID- 27028748
TI  - Case of giant cell arteritis as a manifestation of immunoglobulin G4-related
      disease.

PMID- 27028746
TI  - Intertrochanteric fractures: a review of fixation methods.

PMID- 27028749
TI  - Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus
      Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled
      Trial.
AB  - INTRODUCTION: The fixed-dose, long-acting bronchodilator combination of
      umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a
      combination of a long-acting muscarinic antagonist and long-acting beta2-agonist
      in patients with chronic obstructive pulmonary disease (COPD). METHODS: This 12
      week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study
      compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg +
      indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD. The
      primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85
      (predefined non-inferiority margin -50 mL), and the secondary endpoint was the 0-
      to 6-h weighted mean (WM) FEV1 on day 84. Other efficacy endpoints [including
      rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the
      St. George's Respiratory Questionnaire (SGRQ) score] and safety endpoints
      [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.
      RESULTS: Trough FEV1 improvements were comparable between treatment groups [least
      squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171
      mL; treatment difference 1 mL; 95 % confidence interval (CI) -29 to 30 mL],
      demonstrating non-inferiority between UMEC/VI and TIO + IND. The treatments
      produced similar improvements in the trough FEV1 at other study visits and the 0-
      to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL;
      treatment difference -23 mL; 95 % CI -54 to 8 mL). The results for patient
      reported measures (rescue medication use, TDI focal score, and SGRQ score) were
      comparable; both treatments produced clinically meaningful improvements in TDI
      and SGRQ scores. The incidence of AEs and COPD exacerbations, and changes in
      vital signs were similar for the two treatments. CONCLUSION: UMEC/VI and TIO +
      IND, given once daily, provided similar improvements in lung function and patient
      reported outcomes over 12 weeks in patients with COPD, with comparable
      tolerability and safety profiles. TRIAL NUMBERS: ClinicalTrials.gov study ID
      NCT02257385; GSK study no. 116961.

PMID- 27028750
TI  - Randomized Comparative Bioavailability of a Novel Three-Dimensional Printed Fast
      Melt Formulation of Levetiracetam Following the Administration of a Single 1000
      mg Dose to Healthy Human Volunteers Under Fasting and Fed Conditions.
AB  - BACKGROUND: Rapidly disintegrating or 'fast-melt' oral formulations have been
      developed recently to facilitate drug intake among patients. Even though these
      formulations have helped to improve therapy adherence, some of their limitations
      include: the dissolution time, their facility to be swallowed, and the dosage
      strengths that may be accommodated. To overcome these limitations, a novel,
      porous, quickly disintegrating, and easier-to-swallow fast-melt formulation based
      on powder-liquid, three-dimensional printing (3DP) technology has been developed.
      OBJECTIVE: To determine and compare the relative bioavailability of a novel 3DP
      fast melt containing levetiracetam in healthy male and female subjects. METHODS:
      This study included 33 subjects in a three-way crossover design. The 3DP fast
      melt formulation was compared against the conventional immediate-release tablet
      of levetiracetam (Keppra((r))) after a single 1000-mg dose administration under
      fasting conditions following the bioequivalence criteria used by the US Food and
      Drug Administration. This study also evaluated the food effect on the
      bioavailability of the levetiracetam 3DP fast melt. A small sip of liquid was
      used to administer the fast-melt formulation. RESULTS: The novel 3DP fast melt
      showed rapid oral disintegration (mean duration of 11 s from a sip of water to
      completion of swallowing) following its administration, and did not affect the
      pharmacokinetic profile of levetiracetam. A lower absorption peak was observed
      after administration of the 3DP fast melt under fed conditions, as expected. In
      addition, time of maximum measured plasma concentration was delayed by
      approximately 3.5 h under fed conditions. These effects are unlikely to be of
      clinical significance with long-term administration, and may help reduce the
      adverse events and facilitate compliance. Finally, no change in the oral mucosa
      was observed with the 3DP fast melt while being as safe and well tolerated as the
      standard levetiracetam tablet. CONCLUSION: This study quantified the rapid
      disintegration of the 3DP levetiracetam fast melt and confirmed its equivalent
      rate and extent of absorption to the conventional immediate-release tablet in the
      fasted state, using standard bioequivalence criteria.

PMID- 27028751
TI  - Investigation of Metabolite Profile of YM758, a Novel If Channel Inhibitor.
AB  - BACKGROUND: YM758 monophosphate is a novel If channel inhibitor that has an
      inhibitory action for If current and shows a strong and specific activity,
      selectively lowering the heart rate and decreasing oxygen consumption by heart
      muscle. OBJECTIVES: The objectives of the current study were to investigate the
      in vivo metabolic profiles of YM758 in mice, rats, rabbits, dogs, and monkeys and
      to elucidate the structures of YM758 metabolites. METHODS: Biological samples
      were analyzed by liquid chromatography hyphenated with a radiometric detection
      system and liquid chromatography coupled with a mass spectrometer to clarify
      their metabolic patterns. To elucidate their structures, metabolites were
      isolated and analyzed by mass spectrometry and nuclear magnetic resonance
      spectroscopy. RESULTS: Our results from in vivo metabolic profiling in humans and
      animals indicated there is no significant species difference in the metabolism of
      YM758, and the metabolic pathways of YM758 are considered to be oxidation,
      hydration, and demethylation followed by sulfate or glucuronide conjugation.

PMID- 27028752
TI  - Atherosclerosis and vasomotor dysfunction in arteries of animals after exposure
      to combustion-derived particulate matter or nanomaterials.
AB  - Exposure to particulate matter (PM) from traffic vehicles is hazardous to the
      vascular system, leading to clinical manifestations and mortality due to ischemic
      heart disease. By analogy, nanomaterials may also be associated with the same
      outcomes. Here, the effects of exposure to PM from ambient air, diesel exhaust
      and certain nanomaterials on atherosclerosis and vasomotor function in animals
      have been assessed. The majority of studies have used pulmonary exposure by
      inhalation or instillation, although there are some studies on non-pulmonary
      routes such as the gastrointestinal tract. Airway exposure to air pollution
      particles and nanomaterials is associated with similar effects on atherosclerosis
      progression, augmented vasoconstriction and blunted vasorelaxation responses in
      arteries, whereas exposure to diesel exhaust is associated with lower responses.
      At present, there is no convincing evidence of dose-dependent effects across
      studies. Oxidative stress and inflammation have been observed in the arterial
      wall of PM-exposed animals with vasomotor dysfunction or plaque progression. From
      the data, it is evident that pulmonary and systemic inflammation does not seem to
      be necessary for these vascular effects to occur. Furthermore, there is
      inconsistent evidence with regard to altered plasma lipid profile and systemic
      inflammation as a key step in vasomotor dysfunction and progression of
      atherosclerosis in PM-exposed animals. In summary, the results show that certain
      nanomaterials, including TiO2, carbon black and carbon nanotubes, have similar
      hazards to the vascular system as combustion-derived PM. 

PMID- 27028753
TI  - Preserving Parathyroid Gland Vasculature to Reduce Post-thyroidectomy
      Hypocalcemia.
AB  - BACKGROUND: The failure to preserve parathyroid function in patients who have
      undergone total thyroidectomy is of major concern, because hypocalcemia is
      difficult to prevent and remains a common postoperative complication. Here, we
      describe procedures designed to preserve the vasculature supplying the
      parathyroid glands and examine both recent outcomes and retrospective reports of
      results obtained prior to the application of these preservation techniques.
      METHODS: Our technique for preserving parathyroid function during thyroidectomy
      was adopted in 2009 and involves separating a relatively long segment of a vessel
      distally from the thyroid gland. We reviewed the medical records of 1,411
      patients who underwent total thyroidectomy, with or without lateral neck
      dissection, at the Samsung Medical Center from January 2006 through June 2014 to
      determine outcomes. Patients were divided into three groups according to the time
      period during which the surgery took place: Group A, 2006-2008 (before the
      vasculature-preserving technique was applied); Group B, 2009-2011 (the time when
      the technique was first adopted); and Group C, 2012-2014 (more recent results of
      the technique). We analyzed the incidence of hypoparathyroidism in the three
      groups, as well as risk factors that influenced its development. RESULTS: The
      rates of transient and permanent hypoparathyroidism in Group A were 25.4 and 4.3
      %, respectively. However, the incidence of hypoparathyroidism decreased
      significantly over time after the vasculature-preserving procedure was adopted.
      Transient hypoparathyroidism developed in 4.8 % of Group C patients, and only
      four (0.7 %) of the 565 patients in this group required calcium supplementation,
      despite the fact that a greater number of patients were included who underwent
      total thyroidectomy combined with lateral neck dissection. Although female sex
      and lateral neck dissection tended to increase the rate of transient
      hypoparathyroidism, multivariate analysis showed that the vasculature-preserving
      procedure was the only significant risk factor related to postoperative
      hypoparathyroidism. CONCLUSION: The blood flow of the final branch to the
      parathyroid gland is mostly in the lateral-to-medial direction; therefore,
      mobilization and preservation of the vessels lateral to the gland is essential to
      prevent devascularization of the parathyroid gland.

PMID- 27028754
TI  - Land-use change affects water recycling in Brazil's last agricultural frontier.
AB  - Historically, conservation-oriented research and policy in Brazil have focused on
      Amazon deforestation, but a majority of Brazil's deforestation and agricultural
      expansion has occurred in the neighboring Cerrado biome, a biodiversity hotspot
      comprised of dry forests, woodland savannas, and grasslands. Resilience of
      rainfed agriculture in both biomes likely depends on water recycling in
      undisturbed Cerrado vegetation; yet little is known about how changes in land-use
      and land-cover affect regional climate feedbacks in the Cerrado. We used remote
      sensing techniques to map land-use change across the Cerrado from 2003 to 2013.
      During this period, cropland agriculture more than doubled in area from 1.2 to
      2.5 million ha, with 74% of new croplands sourced from previously intact Cerrado
      vegetation. We find that these changes have decreased the amount of water
      recycled to the atmosphere via evapotranspiration (ET) each year. In 2013 alone,
      cropland areas recycled 14 km(3) less (-3%) water than if the land cover had been
      native Cerrado vegetation. ET from single-cropping systems (e.g., soybeans) is
      less than from natural vegetation in all years, except in the months of January
      and February, the height of the growing season. In double-cropping systems (e.g.,
      soybeans followed by corn), ET is similar to or greater than natural vegetation
      throughout a majority of the wet season (December-May). As intensification and
      extensification of agricultural production continue in the region, the impacts on
      the water cycle and opportunities for mitigation warrant consideration. For
      example, if an environmental goal is to minimize impacts on the water cycle,
      double cropping (intensification) might be emphasized over extensification to
      maintain a landscape that behaves more akin to the natural system.

PMID- 27028755
TI  - Conserved transmembrane glycine residues in the Shigella flexneri polysaccharide
      co-polymerase protein WzzB influence protein-protein interactions.
AB  - The O antigen (Oag) component of lipopolysaccharides (LPS) is crucial for
      virulence and Oag chain-length regulation is controlled by the polysaccharide co
      polymerase class 1 (PCP1) proteins. Crystal structure analyses indicate that
      structural conservation among PCP1 proteins is highly maintained, however the
      mechanism of Oag modal-chain-length control remains to be fully elucidated.
      Shigella flexneri PCP1 protein WzzBSF confers a modal-chain length of 10-17 Oag
      repeat units (RUs), whereas the Salmonella enterica Typhimurium PCP1 protein
      WzzBST confers a modal-chain length of ~16-28 Oag RUs. Both proteins share >70 %
      overall sequence identity and contain two transmembrane (TM1 and TM2) regions,
      whereby a conserved proline-glycine-rich motif overlapping the TM2 region is
      identical in both proteins. Conserved glycine residues within TM2 are
      functionally important, as glycine to alanine substitutions at positions 305 and
      311 confer very short Oag modal-chain length (~2-6 Oag RUs). In this study,
      WzzBSF was co-expressed with WzzBST in S. flexneri and a single intermediate
      modal-chain length of ~11-21 Oag RUs was observed, suggesting the presence of
      Wzz:Wzz interactions. Interestingly, co-expression of WzzBSF with WzzBG305A/G311A
      conferred a bimodal LPS Oag chain length (despite over 99 % protein sequence
      identity), and we hypothesized that the proteins fail to interact. Co
      purification assays detected His6-WzzBSF co-purifying with FLAG-tagged WzzBST but
      not with FLAG-tagged WzzBG305A/G311A, supporting our hypothesis. These data
      indicate that the conserved glycine residues in TM2 are involved in Wzz:Wzz
      interactions, and provide insight into key interactions that drive Oag modal
      length control.

PMID- 27028756
TI  - Probiotic Bacterial and Fungal Strains: Claims with Evidence.
AB  - BACKGROUND: Probiotics are live microorganisms that, when administered in
      adequate amounts, confer a health benefit for the host. This review summarizes
      current (i.e. published in the last 5 years) key evidence on probiotic efficacy
      and its safety in adults and children. To identify relevant data, searches of
      MEDLINE and the Cochrane Library databases were performed in August 2015 to
      locate randomized controlled trials (RCTs) or their meta-analyses. The focus was
      on commonly used, well-specified, bacterial and yeast probiotics for the
      treatment of gastrointestinal disorders. The MEDLINE database was also searched
      for evidence-based clinical practice guidelines, developed by scientific
      societies in the same timeframe. Data on safety of probiotics were obtained from
      a document developed by the US Agency for Healthcare Research and Quality. KEY
      MESSAGES: A number of relevant RCTs and meta-analyses are available.
      Saccharomyces boulardii is the most studied yeast probiotic, and Lactobacillus
      rhamnosus GG is the most studied bacterial probiotic. For both, the best
      documented fact is their efficacy for the treatment of acute gastroenteritis,
      especially in children, and for the prevention of antibiotic-associated diarrhea,
      both in adults and children. There is some evidence to support the use of
      probiotics to prevent or treat other diseases, such as necrotizing enterocolitis,
      infantile colic, Helicobacter pylori infection, and irritable bowel syndrome, but
      further studies are needed to identify which strain(s) is/are the most effective.
      Data on safety, particularly long-term safety, are limited. The risk of side
      effects is greater in people who have severe underlying health conditions.
      CONCLUSIONS: The evidence on bacterial and yeast probiotics has considerably
      expanded during recent years. Accumulated data allow one to make informed
      decisions about the effectiveness of probiotics and about how to reduce the use
      of those without proven efficacy.

PMID- 27028757
TI  - Mechanism Underlying the Spatial Pattern Formation of Dominant Tree Species in a
      Natural Secondary Forest.
AB  - Studying the spatial pattern of plant species may provide significant insights
      into processes and mechanisms that maintain stand stability. To better understand
      the dynamics of naturally regenerated secondary forests, univariate and bivariate
      Ripley's L(r) functions were employed to evaluate intra-/interspecific
      relationships of four dominant tree species (Populus davidiana, Betula
      platyphylla, Larix gmelinii and Acer mono) and to distinguish the underlying
      mechanism of spatial distribution. The results showed that the distribution of
      soil, water and nutrients was not fragmented but presented clear gradients. An
      overall aggregated distribution existed at most distances. No correlation was
      found between the spatial pattern of soil conditions and that of trees. Both
      positive and negative intra- and interspecific relationships were found between
      different DBH classes at various distances. Large trees did not show systematic
      inhibition of the saplings. By contrast, the inhibition intensified as the height
      differences increased between the compared pairs. Except for Larix, universal
      inhibition of saplings by upper layer trees occurred among other species, and
      this reflected the vertical competition for light. Therefore, we believe that
      competition for light rather than soil nutrients underlies the mechanism driving
      the formation of stand spatial pattern in the rocky mountainous areas examined. 

PMID- 27028758
TI  - Longitudinal Changes in Glucose Metabolism of Denervated Muscle after Complete
      Peripheral Nerve Injury.
AB  - PURPOSE: Electrodiagnostic studies can obtain information 2 or 3 weeks after an
      acute nerve injury. Previous studies have shown increased glucose metabolism in
      denervated muscles 1 week after injury using 2-deoxy-2-[(18)F]fluoro-D-glucose
      ([(18)F]FDG) positron emission tomography (PET). Therefore, this study aimed to
      evaluate the changes in glucose metabolism in denervated muscles using serial
      monitoring by [(18)F]FDG PET scans. PROCEDURES: Denervation was induced in eight
      male Sprague-Dawley rats (aged 7 weeks old) weighing 200-250 g. The right legs of
      the rats were denervated by resecting the sciatic nerve in the thigh after the
      initial skin incision. Two rats were sacrificed 1 and 10 weeks after denervation.
      Skeletal muscles (gastrocnemius and tibialis anterior) were excised from both the
      right and left legs of the rats. Staining with hematoxylin and eosin, glucose
      transporter (GLUT)-1, GLUT-4, and hexokinase II was undertaken. PET/computed
      tomography (CT) scans were performed on the six remaining rats a total of five
      times at 1, 2, 5, 8, and 10 weeks after denervation. Regions of interest were
      drawn on integrated PET/CT images to measure the degree of [(18)F]FDG uptake in
      the right and left lower leg muscles. Target-to-background ratios (TBRs) were
      calculated by dividing the FDG uptake of the lower leg muscles by that of the
      upper leg muscles. RESULTS: The TBRs of the denervated muscles were higher than
      those of the control muscles at both 1 (6.84 +/- 1.98 vs. 1.18 +/- 0.11, p =
      0.009) and 2 (4.10 +/- 2.05 vs. 1.86 +/- 0.73, p = 0.0374) weeks after
      denervation. After 5 (2.18 +/- 0.78 vs. 1.35 +/- 0.47, p = 0.1489), 8 (1.76 +/-
      0.18 vs. 1.69 +/- 0.18, p = 0.5127), and 10 (1.76 +/- 0.52 vs. 1.56 +/- 0.37, p =
      0.5637) weeks, the difference in the TBRs between the denervated and controls
      became non-significant. CONCLUSIONS: [(18)F]FDG PET can visualize increased
      glucose metabolism in a denervated muscle early as 1 week after injury.
      Therefore, PET could be adopted as a noninvasive imaging modality for acute nerve
      injuries. In addition, [(18)F]FDG PET may help to understand the role of the
      nervous system in the control of peripheral tissues.

PMID- 27028759
TI  - Vaginal progesterone as maintenance treatment after an episode of preterm labour
      (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled
      trial.
AB  - OBJECTIVE: To evaluate whether maintenance treatment with vaginal progesterone
      after an arrested preterm labour reduces the incidence of preterm delivery.
      DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING:
      Twelve tertiary care centres in Spain. POPULATION: A total of 265 women with
      singleton pregnancy, preterm labour successfully arrested with tocolytic
      treatment, and cervical length of <25 mm. METHODS: Randomisation was stratified
      by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0
      weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1
      ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until
      delivery or 36.6 weeks of gestation, whichever occurred first. MAIN OUTCOME
      MEASURES: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation.
      Secondary outcomes were discharge-to-delivery time, readmissions because of
      preterm labour, emergency service use, and neonatal morbidity and mortality.
      RESULTS: From June 2008 through June 2012, 1419 women were screened: 472 met the
      inclusion criteria and 265 were randomised. The final analysis included 258
      women: 126 in the progesterone group and 132 in the placebo group. There were no
      significant differences between the progesterone and placebo groups in terms of
      delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91]
      or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There
      were no differences observed between groups when considering the two strata of
      gestational age at inclusion. CONCLUSIONS: A maintenance treatment of 200 mg of
      daily vaginal progesterone capsules in women discharged home after an episode of
      arrested preterm labour did not significantly reduce the rate of preterm
      delivery. TWEETABLE ABSTRACT: Maintenance progesterone in 258 women after
      arrested PTL showed no benefit.

PMID- 27028760
TI  - Prevalence of mip virulence gene and PCR-base sequence typing of Legionella
      pneumophila from cooling water systems of two cities in Iran.
AB  - Legionella pneumophila is the primary respiratory pathogen and mostly transmitted
      to human through water cooling systems and cause mild to severe pneumonia with
      high mortality rate especially in elderly both in hospitals and community.
      However, current Legionella risk assessments may be compromised by uncertainties
      in Legionella detection methods. Here, we investigated the presence of L.
      pneumophila mip gene in water samples collected from different hospitals cooling
      towers, nursing homes and building/hotels water coolants from two geographical
      locations of Iran (Kerman and Bam cities) during summer season of 2015 by both
      nested and real-time PCR methods. Analysis of the 128 water samples for presence
      of the mip gene by nested-PCR revealed, 18 (23%) positive cases in Kerman and
      7(14%) in Bam. However, when samples were tested by real-time PCR, we identified
      4 more new cases of L. pneumophila in the hospitals as well as nursing homes
      water systems that were missed by nested-PCR. The highest rate of contamination
      was detected in water obtained from hospitals cooling towers in both the cities
      (p<=0.05). Dendrogram analysis and clonal relationship by PCR-base sequence
      typing (SBT) of the L. pneumophila genomic DNAs in Kerman water samples showed
      close clonal similarities among the isolates, in contrast, isolates identified
      from Bam city demonstrated two fingerprint patterns. The clones from hospital
      water samples were more related to the L. pneumophila serogroup- 1.

PMID- 27028761
TI  - Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse
      Model.
AB  - Bipolar disorder, also known as manic-depressive illness, causes swings in mood
      and activity levels at irregular intervals. Such changes are difficult to
      predict, and their molecular basis remains unknown. Here, we use infradian
      (longer than a day) cyclic activity levels in alphaCaMKII (Camk2a) mutant mice as
      a proxy for such mood-associated changes. We report that gene-expression patterns
      in the hippocampal dentate gyrus could retrospectively predict whether the mice
      were in a state of high or low locomotor activity (LA). Expression of a subset of
      circadian genes, as well as levels of cAMP and pCREB, possible upstream
      regulators of circadian genes, were correlated with LA states, suggesting that
      the intrinsic molecular circuitry changes concomitant with infradian oscillatory
      LA. Taken together, these findings shed light onto the molecular basis of how
      irregular biological rhythms and behavior are controlled by the brain. 

PMID- 27028762
TI  - Kruppel Expression Levels Are Maintained through Compensatory Evolution of Shadow
      Enhancers.

PMID- 27028763
TI  - Relationship between periodontal disease and asthma among overweight/obese
      adults.
AB  - AIM: To assess the relationship between oral health and asthma. METHODS: Data
      from 1315 overweight or obese individuals, aged 40-65 years were used. Asthma was
      self-reported, whereas periodontitis, bleeding on probing (BOP) and plaque index
      were determined by clinical examinations. RESULTS: Using logistic regression
      adjusting for gender, smoking status, age, body mass index, family history of
      asthma and income level, revealed that the odds ratio (OR) of asthma for a
      participant with severe periodontitis was 0.44 (95% confidence interval: 0.27,
      0.70) that of a participant with none/mild periodontitis. On the other hand,
      proportion of BOP sites and plaque index were not statistically significant. For
      a participant with severe periodontitis, the OR of taking asthma medication was
      0.20 (95% confidence interval: 0.09, 0.43) that of a participant with none/mild
      periodontitis. Moreover, proportion of BOP sites was statistically associated
      with use of asthma medication, whereas plaque index still remained non
      significant. CONCLUSION: Participants with severe periodontitis were less likely
      to have asthma. Stronger evidence of an inverse association was found when using
      asthma medication as outcome.

PMID- 27028764
TI  - The MKK7 p.Glu116Lys Rare Variant Serves as a Predictor for Lung Cancer Risk and
      Prognosis in Chinese.
AB  - Accumulated evidence indicates that rare variants exert a vital role on
      predisposition and progression of human diseases, which provides neoteric
      insights into disease etiology. In the current study, based on three
      independently retrospective studies of 5,016 lung cancer patients and 5,181
      controls, we analyzed the associations between five rare polymorphisms (i.e.,
      p.Glu116Lys, p.Asn118Ser, p.Arg138Cys, p.Ala195Thr and p.Leu259Phe) in MKK7 and
      lung cancer risk and prognosis. To decipher the precise mechanisms of MKK7 rare
      variants on lung cancer, a series of biological experiments was further
      performed. We found that the MKK7 p.Glu116Lys rare polymorphism was significantly
      associated with lung cancer risk, progression and prognosis. Compared with
      Glu/Glu common genotype, the 116Lys rare variants (Lys/Glu/+ Lys/Lys) presented
      an adverse effect on lung cancer susceptibility (odds ratio [OR] = 3.29, 95%
      confidence interval [CI] = 2.70-4.01). These rare variants strengthened patients'
      clinical progression that patients with 116Lys variants had a significantly
      higher metastasis rate and advanced N, M stages at diagnosis. In addition, the
      patients with 116Lys variants also contributed to worse cancer prognosis than
      those carriers with Glu/Glu genotype (hazard ratio [HR] = 1.53, 95% CI = 1.32
      1.78). Functional experiments further verified that the MKK7 p.116Lys variants
      altered the expression of several cancer-related genes and thus affected lung
      cancer cells proliferation, tumor growth and metastasis in vivo and in vitro.
      Taken together, our findings proposed that the MKK7 p.Glu116Lys rare polymorphism
      incurred a pernicious impact on lung cancer risk and prognosis through modulating
      expressions of a serial of cancer-related genes. 

PMID- 27028765
TI  - Morphology of Imidazolium-Based Ionic Liquids as Deposited by Vapor Deposition:
      Micro-/Nanodroplets and Thin Films.
AB  - The morphology of micro- and nanodroplets and thin films of ionic liquids (ILs)
      prepared through physical vapor deposition is presented. The morphology of
      droplets deposited on indium-tin-oxide-coated glass is presented for the extended
      1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Cn C1 im][Ntf2 ];
      n=1-8) series, and the results show the nanostructuration of ILs. The use of in
      vacuum energetic particles enhances/increases the nanodroplets
      mobility/coalescence mechanisms and can be a pathway to the fabrication of thin
      IL films. 

PMID- 27028766
TI  - Ligating coronary vein varices: An effective treatment of "coronary vein steal"
      to increase portal flow in liver transplantation.

PMID- 27028767
TI  - Color Depth Modulation and Resolution in Phase-Change Material Nanodisplays.
AB  - The demonstration of non-volatile color-depth modulation in novel phase change
      nanodisplays allowing for continuous "grayscale" images with ultrahigh resolution
      and low dimensionality is described. These results hold promise for a new
      generation of bistable, ultrahigh-resolution, and flexible display technologies,
      while allowing for other potential applications in nanophotonics and
      optoelectronics. 

PMID- 27028768
TI  - Prevalence of drink-driving among adults in China: A nationally representative
      survey in 2010.
AB  - OBJECTIVE: We examined the prevalence of and characteristics associated with
      drink-driving in China. We compared this study's drink-driving findings with
      those from the United States to explore how effective traffic safety
      interventions from Western cultures might be adapted for use in China. METHODS:
      Data from the 2010 China Chronic Disease and Risk Factor Survey were analyzed to
      describe the prevalence and characteristics associated with drink-driving in
      China. RESULTS: Overall, 1.5% of Chinese adults reported drink-driving in the
      past 30 days-3% of males and 0.1% of females. However, among males who had driven
      a vehicle in the past 30 days and consumed at least one alcoholic beverage in the
      past 30 days, 19% reported drink-driving during the 30-day period. Excessive
      drinking, binge drinking, nonuse of seat belts, and having been injured in a road
      traffic crash in the past year were most strongly associated with drink-driving
      among males. CONCLUSIONS: Drink-driving is prevalent among male drivers in China.
      Although large differences exist between China and the United States in the
      proportion of adults who drive, the proportion who consume alcohol, and some of
      the personal characteristics of those who drink and drive, similarities between
      the 2 countries are present in patterns of risk behaviors among drink-driving. To
      reduce injuries and deaths from drink-driving, effective interventions from
      Western cultures need to be tailored for adoption in China.

PMID- 27028769
TI  - Age of acquisition ratings score better on criterion validity than frequency
      trajectory or ratings "corrected" for frequency.
AB  - From the very first studies on the effect of age of acquisition (AoA) on word
      processing, researchers have validated their AoA ratings by correlating them with
      other, more objective indices of the age at which children know words. Still, the
      ratings have been questioned, and alternative measures have been proposed. Two of
      these are differences in word frequency between language directed at young
      children and language directed at older children (frequency trajectory) and AoA
      ratings corrected for word frequency. Surprisingly, the criterion validity of
      these alternative measures has never been established, partly because one of the
      validation criteria (the age at which children are able to name pictures) has
      been questioned. In the present study, four databases are used that aimed to
      establish the order of English word acquisition, going from the very first words
      learned to words taught in secondary education. The criteria for word knowledge
      included word production, multiple-choice questions about the meaning of the
      words, and teacher judgments about when words should be taught in the school
      curriculum. For all databases, the frequency trajectory correlated substantially
      less with the criterion than AoA ratings. For all but one, the same was true for
      AoA ratings "corrected" for other variables. On the basis of these findings,
      researchers should be cautious interpreting null effects with the "improved"
      variables as evidence against a genuine AoA effect.

PMID- 27028770
TI  - Clinical Practice Guidelines for Pediatric Complicated Appendicitis: The Value in
      Discipline.

PMID- 27028771
TI  - Pain After Unilateral Total Knee Arthroplasty: A Prospective Randomized
      Controlled Trial Examining the Analgesic Effectiveness of a Combined Adductor
      Canal Peripheral Nerve Block with Periarticular Infiltration Versus Adductor
      Canal Nerve Block Alone Versus Periarticular Infiltration Alone.
AB  - BACKGROUND: Total knee arthroplasty is a painful surgery that requires early
      mobilization for successful joint function. Multimodal analgesia, including
      spinal analgesia, nerve blocks, periarticular infiltration (PI), opioids, and
      coanalgesics, has been shown to effectively manage postoperative pain. Both
      adductor canal (AC) and PI have been shown to manage pain without significantly
      impairing motor function. However, it is unclear which technique is most
      effective. This 3-arm trial examined the effect of AC block with PI (AC + PI)
      versus AC block only (AC) versus PI only (PI). The primary outcome was pain on
      walking at postoperative day (POD) 1. METHODS: One hundred fifty-one patients
      undergoing unilateral total knee arthroplasty were included. Patients received
      either AC block with 30 mL of 0.5% ropivacaine or sham block. PI was performed
      intraoperatively with a 110-mL normal saline solution containing 300 mg
      ropivacaine, 10 mg morphine, and 30 mg ketorolac. Those patients randomly
      assigned to AC only received normal saline knee infiltration. RESULTS: On POD 1,
      participants who received AC + PI reported significantly lower pain numeric
      rating scale scores on walking (3.3) compared with those who received AC (6.2) or
      PI (4.9) (P < 0.0001). Participants who received AC reported significantly higher
      pain scores at rest and knee bend compared with those who received AC + PI or PI
      (P < 0.0001). The difference in pain scores between participants who received AC
      + PI and those who received AC was 2.83 (95% confidence interval, 1.58-4.09) and
      the difference between those who received AC + PI and those who received PI was
      1.61 (95% confidence interval, 0.37-2.86). On POD 2, participants who received AC
      + PI reported significantly less pain on walking (4.4) compared with those who
      received AC (5.6) or PI (5.6) (P = 0.006). On POD 2, there was no difference
      between the groups for pain at rest or knee bending. Participants who received AC
      used more IV patient-controlled analgesia on POD 0. There was no difference
      between the groups regarding distance walked. CONCLUSIONS: Participants who
      received AC + PI reported significantly less pain on walking on PODs 1 and 2
      compared with those who received AC only or PI only.

PMID- 27028772
TI  - The Sounds of Desaturation: A Survey of Commercial Pulse Oximeter Sonifications.
AB  - BACKGROUND: The pulse oximeter has been a standard of care medical monitor for
      >25 years. Most manufacturers include a variable-pitch pulse tone in their pulse
      oximeters. Research has shown that the acoustic properties of variable-pitch
      tones are not standardized. In this study, we surveyed the properties of pulse
      tones from 21 pulse oximeters, consisting of 1 to 4 instruments of 11 different
      models and 8 brands. Our goals were to fully document the sounds over saturation
      values 0% to 100%, test whether tones become quieter at low saturation values,
      and create a public repository of pulse oximeter recordings for future use.
      METHODS: A convenience sample of commercial pulse oximeters in use at one
      hospital was studied. Audiovisual recordings of each pulse oximeter's display and
      sounds were taken while it monitored a simulator starting at a saturation of 100%
      and slowly decreasing in 1% steps until the saturation reached 0%. Recorded pulse
      tones were analyzed for spectral frequency and total power. Audio files for each
      pulse oximeter containing 100 pulse tones, one at every saturation value, were
      created for inclusion in the repository. RESULTS: Recordings containing 509 to
      1053 pulse tones were made from the 21 pulse oximeters. Fundamental frequencies
      at 100% saturation ranged from 479 to 921 Hz, and fundamental frequencies at 1%
      saturation ranged from 38 to 404 Hz. The pulse tones from all but one model pulse
      oximeter contained harmonics. Pulse tone step sizes were linear in 6 models and
      logarithmic in 6 models. Only 6 pulse oximeter models decreased the pulse tone
      pitch at every decrease in saturation; all others decreased the pitch at only
      select saturation thresholds. Five pulse oximeter models stopped decreasing pitch
      altogether once the saturation reached a certain lower threshold. Pulse tone
      power (perceived as loudness) changed with saturation level for all pulse
      oximeters, increasing above baseline as saturation decreased from 100% and
      decreasing to levels below baseline at low saturation values. CONCLUSIONS:
      Current pulse oximeters use different techniques to address the competing goals
      of (1) using pitch steps that are large enough to be readily perceived, and (2)
      conveying saturation values from 0 to 100 within a limited range of sound
      frequencies. From a clinical perspective, 2 techniques for increasing
      perceivability (increasing the frequency range and using ratio step sizes) have
      no drawback, but 2 techniques (not changing pitch at every saturation change and
      using a lower saturation cutoff) do have potential clinical drawbacks. On the
      basis of our findings, we have made suggestions for clinicians and manufacturers.

PMID- 27028773
TI  - The Association Between Progesterone, Estradiol, and Oxytocin and Heat Pain
      Measures in Pregnancy: An Observational Cohort Study.
AB  - BACKGROUND: Hormonal action has been implicated as a possible mechanism for
      pregnancy-induced analgesia. Previous investigators have reported an increase in
      heat pain tolerance during labor compared with nonpregnant controls and
      postulated it was because of the hormonal changes during pregnancy. However,
      these previous reports did not include measurement of hormonal values. The
      purpose of our study was to quantitatively test if changes in pregnancy hormone
      concentrations correlated with changes in temperature ratings. METHODS: This was
      a prospective cohort study consisting of 32 women scheduled for elective cesarean
      delivery at term between July 2010 and January 2013. Heat pain threshold and
      tolerance, estrogen, progesterone, and oxytocin levels were measured twice in
      each patient at term and again 4 to 8 weeks postpartum. RESULTS: All hormone
      levels decreased significantly between term pregnancy and the postpartum visit
      (all P values < 0.029). However, there were no statistically significant
      differences between term and postpartum heat pain measurements. The mean baseline
      heat pain threshold was 40.9 degrees C at term compared with 40.3 degrees C 
      degrees postpartum (P = 0.47; mean change, -0.6 degrees C; 95% confidence
      interval of change, -1.8 degrees C to +0.7 degrees C). The mean baseline heat
      pain tolerance was 46.1 degrees C at term and 46.0 degrees C postpartum (P =
      0.59; mean change, -0.1 degrees C; 95% confidence interval of change, -0.8
      degrees C degrees  to +0.6 degrees C). CONCLUSIONS: Our findings show that
      amounts of estradiol and progesterone changed significantly between the term and
      the postpartum visit; however, the thermal pain tolerance did not significantly
      change. In summary, we did not observe an association between hormonal changes
      and changes in pain threshold measures. This finding argues against the concept
      of simple progesterone- or estrogen-induced analgesia in humans.

PMID- 27028774
TI  - Predictors of Difficult Intubation with the Bonfils Rigid Fiberscope.
AB  - BACKGROUND: Endotracheal intubation is commonly performed via direct laryngoscopy
      (DL). However, in certain patients, DL may be difficult or impossible. The
      Bonfils Rigid Fiberscope(r) (BRF) is an alternative intubation device, the design
      of which raises the question of whether factors that predict difficult DL also
      predict difficult BRF. We undertook this study to determine which demographic,
      morphologic, and morphometric factors predict difficult intubation with the BRF.
      METHODS: Four hundred adult patients scheduled for elective surgery were
      recruited. Patients were excluded if awake intubation, rapid sequence induction,
      or induction without neuromuscular blocking agents was planned. Data were
      recorded, including age, sex, weight, height, American Society of
      Anesthesiologist classification, history of snoring and sleep apnea, Mallampati
      class, upper lip bite test score, interincisor, thyromental and sternothyroid
      distances, manubriomental distances in flexion and extension, neck circumference,
      maximal neck flexion and extension, neck skinfold thickness at the cricoid
      cartilage, and Cormack and Lehane grade obtained via DL after paralysis was
      confirmed. Quality of glottic visualization (good or poor), as well as the number
      of intubation attempts and time to successful intubation with the BRF, was noted.
      Univariate analyses were performed to evaluate the association between patient
      characteristics and time required for intubation. Variables that exhibited a
      significant correlation were included in a multivariate analysis using a standard
      least squares model. A P < 0.05 was considered significant. RESULTS: Glottic
      visualization with the BRF was good in 396 of 400 (99%) cases. On the first
      attempt, 390 patients were successfully intubated with the BRF; 6 patients
      required >1 attempt; 4 patients could not be intubated by using the BRF alone.
      These 4 patients were intubated by using a combination of DL and BRF (2
      patients), DL and a Frova bougie (1 patient), and DL and an endotracheal tube
      shaped with a semirigid stylet (1 patient). Mean time for successful intubation
      was 26 +/- 13 seconds. Multivariate analysis showed that decreased mouth opening
      (P = 0.008), increased body mass index (P = 0.011), and higher Cormack and Lehane
      grade (P = 0.038) predicted longer intubation times, whereas shorter thyromental
      distance predicted slightly shorter intubation times (P < 0.0001). CONCLUSIONS:
      Mouth opening, body mass index, and high Cormack and Lehane grade predict longer
      intubation times, as with DL. Decreasing thyromental distance predicts slightly
      shorter intubation times with the BRF, possibly because of a design initially
      optimized for a pediatric population with receding chins. These findings, along
      with the high success rate of BRF in this study, and the possibility of further
      increasing success rates by combining BRF with DL, help define the role of BRF
      intubation in contemporary airway management.

PMID- 27028775
TI  - A Multicenter Pilot Study Assessing Regional Cerebral Oxygen Desaturation
      Frequency During Cardiopulmonary Bypass and Responsiveness to an Intervention
      Algorithm.
AB  - BACKGROUND: The purpose of this multicenter pilot study was to: (1) determine the
      frequency of regional cerebral oxygen saturation (rScO2) desaturations during
      cardiac surgery involving cardiopulmonary bypass (CPB); (2) evaluate the accuracy
      of clinician-identified rScO2 desaturations compared with those recorded
      continuously during surgery by the near-infrared spectroscopy (NIRS) monitor; and
      (3) assess the effectiveness of an intervention algorithm for reversing rScO2
      desaturations. METHODS: Two hundred thirty-five patients undergoing coronary
      artery bypass graft and/or valvular surgery were enrolled at 8 US centers in this
      prospective observational study. NIRS (InvosTM 5100C; Covidien) was used to
      monitor rScO2 during surgery. The frequency and magnitude of rScO2 decrements
      >20% from preanesthesia baseline were documented, and the efficacy of a standard
      treatment algorithm for correcting rScO2 was determined. The data from the NIRS
      monitor were downloaded at the conclusion of surgery and sent to the coordinating
      center where the number of clinician-identified rScO2 desaturation events was
      compared with the number detected by the NIRS monitor. RESULTS: The average rScO2
      obtained at baseline (mean +/- SD, 61% +/- 11%; 99% confidence interval, 57%-65%)
      and during CPB (62% +/- 14%; 57%-67%) was not different. However, rScO2 after
      separation from CPB (56% +/- 11%; 53%-60%) was lower than measurements at
      baseline and during CPB (P < 0.001). During CPB, rScO2 desaturations occurred in
      61% (99% confidence interval, 50%-75%) of patients. The area under the curve for
      product of magnitude and duration of the rScO2 was (mean +/- SD, 145.2; 384.8% *
      min). Clinicians identified all patients with an rScO2 desaturation but
      identified only 340 (89.5%) of the 380 total desaturation events. Of the 340
      clinician-identified rScO2 desaturation events, 115 resolved with usual clinical
      care before implementation of the treatment algorithm. For the remaining 225
      events, the treatment algorithm resulted in resolution of the rScO2 desaturation
      in all but 18 patients. CONCLUSIONS: This multicenter pilot study found that 50%
      to 75% of patients undergoing cardiac surgery experience one or more rScO2
      desaturations during CPB. Nearly 10% of desaturation events were not identified
      by clinicians, suggesting that appropriate alarming systems should be adopted to
      alert clinicians of such events. The intervention algorithm was effective in
      reversing clinically identified rScO2 desaturations in the majority of events.

PMID- 27028776
TI  - Preoperative Cognitive Stratification of Older Elective Surgical Patients: A
      Cross-Sectional Study.
AB  - BACKGROUND: Preexisting cognitive impairment is emerging as a predictor of poor
      postoperative outcomes in seniors. We hypothesized that preoperative cognitive
      screening can be performed in a busy preadmission evaluation center and that
      cognitive impairment is prevalent in elective geriatric surgical patients.
      METHODS: We approached 311 patients aged 65 years and older presenting for
      preoperative evaluation before elective surgery in a prospective, observational,
      single-center study. Forty-eight patients were ineligible, and 63 declined. The
      remaining 200 were randomly assigned to the Mini-Cog (N =100) or Clock-in-the-Box
      [CIB; N = 100)] test. Study staff administered the test in a quiet room, and 2
      investigators scored the tests independently. Probable cognitive impairment was
      defined as a Mini-Cog <= 2 or a CIB <= 5. RESULTS: The age of consenting patients
      was 73.7 +/- 6.4 (mean +/- SD) years. There were no significant differences
      between patients randomly assigned to the Mini-Cog and CIB test in age, weight,
      gender, education, ASA physical status, or Charlston Index. Overall, 23% of
      patients met criteria for probable cognitive impairment, and prevalence was
      virtually identical regardless of the test used; 22% screened with the Mini-Cog
      and 23% screened with the CIB scored as having probable cognitive impairment (P =
      1.0 by chi analysis). Both tests had good interrater reliability (Krippendroff
      alpha = 0.86 [0.72-0.93] for Mini-Cog and 1 for CIB). CONCLUSIONS: Preoperative
      cognitive screening is feasible in most geriatric elective surgical patients and
      reveals a substantial prevalence of probable cognitive impairment in this
      population.

PMID- 27028778
TI  - Correction: Actinobacteria Isolated from an Underground Lake and Moonmilk
      Speleothem from the Biggest Conglomeratic Karstic Cave in Siberia as Sources of
      Novel Biologically Active Compounds.

PMID- 27028777
TI  - Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced
      Neuromuscular Block.
AB  - BACKGROUND: Sugammadex is a relatively new molecule that reverses neuromuscular
      block induced by rocuronium. The particular structure of sugammadex traps the
      cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity.
      Dexamethasone shares the same steroidal structure with rocuronium. Studies in
      vitro have demonstrated that dexamethasone interacts with sugammadex, reducing
      its efficacy. In this study, we investigated the clinical relevance of this
      interaction and its influence on neuromuscular reversal. METHODS: In this
      retrospective case-control study, we analyzed data from 45 patients divided into
      3 groups: dexamethasone after induction group (15 patients) treated with 8 mg
      dexamethasone as an antiemetic drug shortly after induction of anesthesia;
      dexamethasone before reversal group (15 patients) treated with dexamethasone just
      before sugammadex injection; and control group (15 patients) treated with 8 mg
      ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg
      rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2
      mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular
      relaxation was monitored with a TOF-Watch(r) system. RESULTS: The control group
      had a recovery time of 154 +/- 54 seconds (mean +/- SD), the dexamethasone after
      induction group 134 +/- 55 seconds, and the dexamethasone before reversal group
      131 +/- 68 seconds. The differences among groups were not statistically
      significant (P = 0.5141). CONCLUSIONS: Our results show that the use of
      dexamethasone as an antiemetic drug for the prevention of postoperative nausea
      and vomiting does not interfere with reversal of neuromuscular blockade with
      sugammadex in patients undergoing elective surgery with general anesthesia in
      contrast to in vitro studies that support this hypothesis.

PMID- 27028779
TI  - The digital revolution in prosthodontics: can it benefit older people?

PMID- 27028780
TI  - Natural killer cells regulate Th1/Treg and Th17/Treg balance in chlamydial lung
      infection.
AB  - Natural killer (NK) cell is an important component in innate immunity, playing a
      critical role in bridging innate and adaptive immunity by modulating the function
      of other immune cells including T cells. In this study, we focused on the role of
      NK cells in regulating Th1/Treg and Th17/Treg balance during chlamydial lung
      infection. We found that NK cell-depleted mice showed decreased Th1 and Th17
      cells, which was correlated with reduced interferon-gamma, interleukin (IL)-12,
      IL-17 and IL-22 production as well as T-bet and receptor-related orphan receptor
      gamma t expression compared with mice treated with the isotype control antibody.
      In contrast, NK cell depletion significantly increased Treg in cell number and
      related transcription factor (Foxp3) expression. The opposite trends of changes
      of Th1/Th17 and Treg led to significant reduction in the Th1/Treg and Th17/Treg
      ratios. The data implicate that NK cells play an important role in host defence
      against chlamydial lung infection, mainly through maintaining Th1/Treg and
      Th17/Treg balance.

PMID- 27028781
TI  - Posterodorsal Medial Amygdala Mediates Tail-Pinch Induced Food Intake in Female
      Rats.
AB  - Comfort eating during periods of stress is a common phenomenon observed in both
      animals and humans. However, the underlying mechanisms of stress-induced food
      intake remain elusive. The amygdala plays a central role in higher-order
      emotional processing and the posterodorsal subnucleus of the medial amygdala
      (MePD), in particular, is involved in food intake. Extra-hypothalamic
      corticotrophin-releasing factor (CRF) is well recognised for mediating
      behavioural responses to stress. To explore the possible role of amygdala CRF
      receptor activation in stress-induced food intake, we evaluated whether a
      stressor such as tail-pinch, which reliably induces food intake, would fail to do
      so in animals bearing bilateral neurotoxic lesions of the MePD. Our results
      showed that ibotenic acid induced lesions of the MePD markedly reduced tail-pinch
      induced food intake in ovariectomised, 17beta-oestradiol replaced rats. In
      addition, intra-MePD (right side only) administration of CRF (0.002 or 0.02 ng)
      via chronically implanted cannulae resulted in a dose-dependent increase in food
      intake, although higher doses of 0.2 and 2 ng CRF had less effect, producing a
      bell shaped curve. Furthermore, intra-MePD (bilateral) administration of the CRF
      receptor antagonist, astressin (0.3 MUg per side) effectively blocked tail-pinch
      induced food intake. These data suggest that the MePD is involved in stress
      induced food intake and that the amygdala CRF system may be a mediator of comfort
      eating.

PMID- 27028782
TI  - The Zika Challenge.

PMID- 27028783
TI  - Synthesis and bioactivity studies on new 4-(3-(4-Substitutedphenyl)-3a,4-dihydro
      3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides.
AB  - A series of new 4-(3-(4-substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2
      yl) benzenesulfonamides (7-12) was synthesized starting from 2-(4
      substitutedbenzylidene)-2,3-dihydro-1H-inden-1-one (1-6) and 4
      hydrazinobenzenesulfonamide. The substituted benzaldehydes from which the key
      intermediate was prepared by introducing 2- or 4-substituents such as fluorine,
      hydroxy, methoxy, or the 3,4,5-trimethoxy moieties. The compounds were tested for
      their cytotoxicity, tumor-specificity and potential as carbonic anhydrase (CA, EC
      4.2.1.1) inhibitors. The 3,4,5-trimethoxy and the 4-hydroxy derivatives showed
      interesting cytotoxic activities, which may be crucial for further anti-tumor
      activity studies, whereas some of these sulfonamides strongly inhibited both
      human (h) cytosolic isoforms hCA I and II. 

PMID- 27028785
TI  - Photo-distributed Stevens-Johnson syndrome associated with oral itraconazole.

PMID- 27028784
TI  - Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent
      Photodynamic Cancer Therapy.
AB  - Conventional photodynamic treatment strategies are based on the principle of
      activating molecular oxygen in situ by light, mediated by a photosensitizer,
      which leads to the generation of reactive oxygen species and thereby causes cell
      death. A diarylethene-derived peptidomimetic is presented that is suitable for
      photodynamic cancer therapy without any involvement of oxygen. This light
      sensitive molecule is not a mediator but is itself the cytotoxic agent. As a
      derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic
      exists in two thermally stable photoforms that are interconvertible by light of
      different wavelengths. The isomer generated by visible light shows much stronger
      toxicity against tumor cells than the UV-generated isomer. First in vivo
      applications are demonstrated on a tumor animal model to illustrate how the
      peptidomimetic can be administered in the less toxic form and then activated
      locally in a solid tumor by visible light.

PMID- 27028786
TI  - Comprehensive analysis of motions in molecular dynamics trajectories of the actin
      capping protein and its inhibitor complexes.
AB  - The actin capping protein (CP) binds to actin filaments to block further
      elongation. The capping activity is inhibited by proteins V-1 and CARMIL
      interacting with CP via steric and allosteric mechanisms, respectively. The
      crystal structures of free CP, CP/V-1, and CP/CARMIL complexes suggest that the
      binding of CARMIL alters the flexibility of CP rather than the overall structure
      of CP, and this is an allosteric inhibition mechanism. Here, we performed
      molecular dynamics (MD) simulations of CP in the free form, and in complex with
      CARMIL or V-1. The resulting trajectories were analyzed exhaustively using Motion
      Tree, which identifies various rigid-body motions ranging from small local
      motions to large domain motions. After enumerating all the motions, CP
      flexibilities with different ligands were characterized by a list of frequencies
      for 20 dominant rigid-body motions, some of which were not identified in previous
      studies. The comparative analysis highlights the influence of the binding of the
      CARMIL peptide to CP flexibility. In free CP and the CP/V-1 complex, domain
      motions around a large crevice between the N-stalk and the CP-S domain occur
      frequently. The CARMIL peptide binds the crevice and suppresses the motions
      effectively. In addition, the binding of the CARMIL peptide enhances and alters
      local motions around the pocket that participates in V-1 binding. These newly
      identified motions are likely to suppress the binding of V-1 to CP. The observed
      changes in CP motion provide insights that describe the mechanism of allosteric
      regulation by CARMIL through modulating CP flexibility. Proteins 2016; 84:948
      956. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028787
TI  - Significant retinopathy in young-onset type 2 vs. type 1 diabetes: a clinical
      observation.
AB  - OBJECTIVE: Little is known about the burden of severe retinal disease between
      young-onset type 2 (T2D) and type 1 diabetes (T1D). This study assessed the
      prevalence of significant retinopathy in young-onset T2D vs. T1D and its
      predictive factors. METHODS: This was a cross-sectional study. Subjects with T1D
      and T2D diagnosed below age 40 were identified from diabetes eye screening
      register. Preproliferative, proliferative, maculopathy changes and/or previous
      laser photocoagulation treatment were considered to have significant retinopathy
      (SigDR). RESULTS: A total of 1306 subjects were identified, of whom 842 and 464
      had T1D and T2D, respectively. The mean age of diagnosis was significantly lower
      in T1D subjects (T1D vs. T2D; 20.1 +/- 10.3 vs. 32.1 +/- 6.0 years, p < 0.0005).
      Although the T2D cohort had shorter diabetes duration (T1D vs. T2D; 20.8 +/- 13.0
      vs. 13.7 +/- 9.0 years, p < 0.0005), the overall prevalence of SigDR was similar
      to T1D (T1D vs. T2D; 21.6 vs. 20.9%, p = NS). After adjusting for diabetes
      duration, the T2D cohort experienced significantly higher prevalence of this
      complication than T1D after 10 years duration. The age threshold beyond which the
      T2D cohort began to experience greater burden of SigDR was approximately 50
      years. The prevalence of any retinopathy after 15 years duration was 75-80% for
      both young-onset cohort. Risk factors for SigDR (older age, diabetes duration,
      systolic BP, HbA1c and creatinine) were similar in both young-onset diabetes
      cohort with poor glycaemic control being the strongest variable. Lower age of T2D
      diagnosis was not a predictive factor. CONCLUSIONS: Irrespective of diabetes
      type, subjects with young-onset diabetes possessed high lifetime risk for
      retinopathy. However, young-onset T2D cohort was more susceptible to severe
      retinal disease with substantial burden of this complication by the fifth decade
      of life.

PMID- 27028788
TI  - Adrenal insufficiency presenting as unexplained hypotension in nocturnal home
      hemodialysis.
AB  - Adrenal insufficiency is a complication of chronic corticosteroid therapy.
      Unexplained hypotension may be a manifestation of an adrenal insufficient state
      in patients with a history of corticosteroid therapy on hemodialysis. We present
      a series of five cases of patients on nocturnal home hemodialysis with
      hypotension as the main manifestation of adrenal insufficiency. Unexplained
      hypotension in patients with a history of corticosteroid therapy should prompt
      the managing clinician to consider adrenal insufficiency as a possible cause.

PMID- 27028789
TI  - Diversity of Kale (Brassica oleracea var. sabellica): Glucosinolate Content and
      Phylogenetic Relationships.
AB  - Recently, kale has become popular due to nutritive components beneficial for
      human health. It is an important source of phytochemicals such as glucosinolates
      that trigger associated cancer-preventive activity. However, nutritional value
      varies among glucosinolates and among cultivars. Here, we start a systematic
      determination of the content of five glucosinolates in 25 kale varieties and 11
      non-kale Brassica oleracea cultivars by HPLC-DAD-ESI-MS(n) and compare the
      profiles with results from the analysis of SNPs derived from a KASP genotyping
      assay. Our results demonstrate that the glucosinolate levels differ markedly
      among varieties of different origin. Comparison of the phytochemical data with
      phylogenetic relationships revealed that the common name kale refers to at least
      three different groups. German, American, and Italian kales differ
      morphologically and phytochemically. Landraces do not show outstanding
      glucosinolate levels. Our results demonstrate the diversity of kale and the
      importance of preserving a broad genepool for future breeding purposes. 

PMID- 27028790
TI  - Fluid Overload Is Associated With Late Poor Outcomes in Neonates Following
      Cardiac Surgery.
AB  - OBJECTIVES: Acute kidney injury is a severe complication of cardiac surgery
      associated with increased morbidity and mortality; yet, acute kidney injury
      classification for neonates remains challenging. We characterized patterns of
      postoperative fluid overload as a surrogate marker for acute kidney injury and as
      a risk factor of poor postoperative outcomes in neonates undergoing cardiac
      surgery. DESIGN: Retrospective cohort study. SETTING: Single, congenital heart
      center destination program. PATIENTS: Four hundred thirty-five neonates
      undergoing cardiac surgery with cardiopulmonary bypass from January 2006 through
      December 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics,
      diagnosis, and perioperative clinical variables were collected, including daily
      weights and serum creatinine levels. A composite poor clinical outcome (death,
      need for renal replacement therapy or extracorporeal life support within 30
      postoperative days) was considered the primary outcome measure. Twenty-one
      neonates (5%) had a composite poor outcome with 7 (2%) requiring renal
      replacement therapy, 8 (2%) requiring extracorporeal life support, and 14 (3%)
      dying between 3 and 30 days post surgery. Neonates with a composite poor outcome
      had significantly higher maximum fluid overload (> 20%) and were slower to
      diurese. A receiver-operating characteristic curve determined that fluid overload
      greater than or equal to 16% and serum creatinine greater than or equal to 0.9 on
      postoperative day 3 were the optimal cutoffs for significant discrimination on
      the primary outcome (area under the curve = 0.71 and 0.76, respectively). In
      multivariable analysis, fluid overload greater than or equal to 16% (adjusted
      odds ratio = 3.7) and serum creatinine adjusted odds ratio 0.9 (adjusted odds
      ratio = 6.6) on postoperative day 3 remained an independent risk factor for poor
      outcome. Fluid overload greater than or equal 16% was also significantly
      associated with cardiac arrest requiring cardiopulmonary resuscitation, prolonged
      ICU stay, and chest reexploration. CONCLUSIONS: This study highlights the
      importance of monitoring fluid balance in the neonatal cardiac surgical
      population and suggests that daily fluid overload, a readily available,
      noninvasive marker of renal function, may be a sensitive and specific predictor
      of adverse outcomes.

PMID- 27028791
TI  - Evaluation of Disseminated Intravascular Coagulation Scores in Critically Ill
      Pediatric Patients.
AB  - OBJECTIVES: Disseminated intravascular coagulation is a complex systemic
      thrombohemorrahgic disorder, which may contribute to organ failure. We aimed to
      compare the detection rate of the disseminated intravascular coagulation, early
      in the course of ICU admission, of the two disseminated intravascular coagulation
      scoring systems defined by International Society on Thrombosis and Hemostasis and
      Japanese Association for Acute Medicine criteria and the prognostic value of
      disseminated intravascular coagulation scores in critically ill pediatric
      patients. DESIGN: Single-center retrospective observational study. SETTING: PICU
      in a tertiary care children's hospital. PATIENTS: Pediatric patients admitted in
      the PICU between January 2013 and December 2014. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: A total of 191 patients were included. Among them,
      15.7% and 29.8% of the patients were diagnosed with disseminated intravascular
      coagulation by International Society on Thrombosis and Hemostasis and Japanese
      Association for Acute Medicine criteria, respectively. The diagnostic concordance
      rate between the International Society on Thrombosis and Hemostasis and Japanese
      Association for Acute Medicine scoring systems was 52.6%. As the Pediatric Risk
      of Mortality III, the modified Sequential Organ Failure Assessment, and the
      Pediatric Multiple Organ Dysfunction Syndrome scores increased, the percentage of
      patients with disseminated intravascular coagulation increased stepwise. The
      disseminated intravascular coagulation scores correlated well with these severity
      scores. Overall, the 28-day mortality was 9.9%. There were significant
      differences in most variables consisting of the International Society on
      Thrombosis and Hemostasis and Japanese Association for Acute Medicine scoring
      systems between survivor and nonsurvivors. Patients detected to have disseminated
      intravascular coagulation by the International Society on Thrombosis and
      Hemostasis and Japanese Association for Acute Medicine scoring systems showed
      higher mortality than patients without disseminated intravascular coagulation.
      The areas under the receiver operating characteristic curve of the Japanese
      Association for Acute Medicine score and International Society on Thrombosis and
      Hemostasis score were 0.788 (95% CI, 0.675-0.900) and 0.716 (95% CI, 0.598
      0.834), respectively. CONCLUSIONS: Both the International Society on Thrombosis
      and Hemostasis and the Japanese Association for Acute Medicine scoring systems
      are useful for detection of the disseminated intravascular coagulation in
      critically ill pediatric patients. These scores correlate well with other
      severity scores, including Pediatric Risk of Mortality III, modified Sequential
      Organ Failure Assessment, and Pediatric Multiple Organ Dysfunction Syndrome.
      Disseminated intravascular coagulation scores are also significantly associated
      with 28-day mortality, suggesting that these could be promising prognostic
      factors.

PMID- 27028792
TI  - Intracranial Hypertension and Cerebral Hypoperfusion in Children With Severe
      Traumatic Brain Injury: Thresholds and Burden in Accidental and Abusive Insults.
AB  - OBJECTIVES: The evidence to guide therapy in pediatric traumatic brain injury is
      lacking, including insight into the intracranial pressure/cerebral perfusion
      pressure thresholds in abusive head trauma. We examined intracranial
      pressure/cerebral perfusion pressure thresholds and indices of intracranial
      pressure and cerebral perfusion pressure burden in relationship with outcome in
      severe traumatic brain injury and in accidental and abusive head trauma cohorts.
      DESIGN: A prospective observational study. SETTING: PICU in a tertiary children's
      hospital. PATIENTS: Children less than18 years old admitted to a PICU with severe
      traumatic brain injury and who had intracranial pressure monitoring.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A pediatric traumatic brain
      injury database was interrogated with 85 patients (18 abusive head trauma)
      enrolled. Hourly intracranial pressure and cerebral perfusion pressure (in mm Hg)
      were collated and compared with various thresholds. C-statistics for intracranial
      pressure and cerebral perfusion pressure data in the entire population were
      determined. Intracranial hypertension and cerebral hypoperfusion indices were
      formulated based on the number of hours with intracranial pressure more than 20
      mm Hg and cerebral perfusion pressure less than 50 mm Hg, respectively. A
      secondary analysis was performed on accidental and abusive head trauma cohorts.
      All of these were compared with dichotomized 6-month Glasgow Outcome Scale
      scores. The models with the number of hours with intracranial pressure more than
      20 mm Hg (C = 0.641; 95% CI, 0.523-0.762) and cerebral perfusion pressure less
      than 45 mm Hg (C = 0.702; 95% CI, 0.586-0.805) had the best fits to discriminate
      outcome. Two factors were independently associated with a poor outcome, the
      number of hours with intracranial pressure more than 20 mm Hg and abusive head
      trauma (odds ratio = 5.101; 95% CI, 1.571-16.563). As the number of hours with
      intracranial pressure more than 20 mm Hg increases by 1, the odds of a poor
      outcome increased by 4.6% (odds ratio = 1.046; 95% CI, 1.012-1.082). Thresholds
      did not differ between accidental versus abusive head trauma. The intracranial
      hypertension and cerebral hypoperfusion indices were both associated with
      outcomes. CONCLUSIONS: The duration of hours of intracranial pressure more than
      20 mm Hg and cerebral perfusion pressure less than 45 mm Hg best discriminated
      poor outcome. As the number of hours with intracranial pressure more than 20 mm
      Hg increases by 1, the odds of a poor outcome increased by 4.6%. Although abusive
      head trauma was strongly associated with unfavorable outcome, intracranial
      pressure/cerebral perfusion pressure thresholds did not differ between accidental
      and abusive head trauma.

PMID- 27028793
TI  - The physiologic coupling of sucking and swallowing coordination provides a unique
      process for neonatal survival.
AB  - AIM: Although the coordination of sucking and swallowing is critical for
      successful oral intake in neonates, the mechanisms that facilitate this
      coordination are not well understood. This investigation sought to clarify the
      mechanisms that facilitate this coordination, by comparing sucks that were
      coordinated with swallows and sucks that were completed in isolation. METHODS:
      Ten neonates with a median gestational age of 28.2 weeks, ranging from 27.0 to
      35.0 weeks, were recruited from the neonatal nurseries at Nationwide Children's
      Hospital, Columbus, Ohio, USA. They were evaluated while bottle-feeding at term
      gestation for differences in characteristics between sucks that were coupled and
      not coupled with swallows. Suction was evaluated using an intra-oral pressure
      transducer, and swallows were identified using a micromanometry pharyngeal
      catheter. Linear mixed models were applied to distinguish sucking
      characteristics. RESULTS: Suction exhibited an antiphase relationship with the
      generation and release of positive pharyngeal pressure during the swallow.
      Coupled sucks had lower suction generation and release rates (p < 0.0001), lower
      suction amplitude (p = 0.004), longer suction duration (p < 0.0001) and higher
      milk ejection pressure (p < 0.0001). CONCLUSION: The coordination of unique
      sucking and swallowing movement patterns may be achieved by the infant adapting
      sucking kinematics around the lingual patterns that facilitate the pharyngeal
      swallow.

PMID- 27028794
TI  - Comparison Between HDL-C Levels in Argentine Indigenous Children Living at High
      Altitudes and U.S. Children.
AB  - BACKGROUND: Studies have shown low levels of high-density lipoprotein cholesterol
      (HDL-C) in indigenous children versus urban children from Argentina. We
      hypothesized that indigenous children living at high altitudes might have lower
      HDL-C levels compared with U.S. children, probably due to ambient hypoxia,
      lifestyle conditions, or ethnicity. This study was designed (1) to compare HDL-C
      levels in Argentinean indigenous children with those reported in the 2011-2012
      National Health and Nutrition Examination Survey (NHANES) for U.S. children and
      (2) to determine the association between HDL-C and adiposity in both groups.
      SUBJECTS AND METHODS: A cross-sectional study of 1,232 (631 females) Argentinean
      indigenous schoolchildren (4-14 years old) from San Antonio de los Cobres (SAC)
      was performed between November 2011 and November 2014. Anthropometric measures
      were performed in the whole group and compared with those of 2,151 U.S. children
      (1,034 females). However, HDL-C concentrations were measured in 905 SAC children
      and compared with those of 1,451 U.S. children. Analyses were done incorporating
      sampling weights for age in both samples to obtain unbiased estimates. In the
      case of NHANES the weights provided by each individual in the 2011-2012 NHANES
      demographic file were used, whereas in the SAC sample the weights were obtained
      using the census data provided by the 2010 National Statistics and Censuses
      Institute of Argentina. RESULTS: The prevalence of overweight/obesity was
      significantly lower in SAC (135/1,232; 11%) than in the United States (759/2,151;
      35%). However, the prevalence of low levels of HDL-C was significantly higher in
      SAC (298/905; 33%) than in the United States (142/1,451; 10%). The prevalence of
      low levels of HDL-C increased significantly in both groups as body mass index
      categories increased. Multiple logistic regression analysis showed that SAC
      children had nine and a half times the odds of having low levels of HDL-C
      compared with U.S. children, adjusted for confounding variables (odds ratio =
      9.55; 95% confidence interval, 7.18-12.71). CONCLUSIONS: This study shows a high
      prevalence of low levels of HDL-C in indigenous Argentinean children 4-14 years
      of age living at high altitudes compared with U.S. children.

PMID- 27028795
TI  - KRYPTOR-automated angiogenic factor assays and risk of preeclampsia-related
      adverse outcomes.
AB  - OBJECTIVE: To evaluate KRYPTOR assays for circulating soluble fms-like tyrosine
      kinase-1 (sFlt1) and placental growth factor (PlGF) in risk assessment of adverse
      outcomes in women with suspected preeclampsia. METHODS: We studied 412 women
      carrying a singleton pregnancy from a previous study cohort who were evaluated
      for suspected preeclampsia. Another 434 nonpreeclamptic patients with plasma
      samples drawn throughout pregnancy were used to derive normative data. Plasma
      sFlt1 and PlGF levels were measured on the automated KRYPTOR platform and
      evaluated for prediction of adverse maternal and perinatal outcomes within 2
      weeks. Normative values were used to create a ratio of markers and these values
      were reported as multiples of median (MoM) for women with and without adverse
      outcomes. The KRYPTOR assay results were also compared with previously reported
      measurements obtained using the automated Elecsys platform. RESULTS: Among
      participants presenting at <34 weeks (N = 110), patients with subsequent adverse
      outcome had higher sFlt1, lower PlGF, and higher sFlt1/PlGF ratio compared with
      women without adverse outcomes: the median (25th, 75th centile) sFlt1 (pg/ml),
      9030 (3197, 12,140) versus 1976 (1248, 2937); PlGF (pg/ml), 36 (16, 111) versus
      318 (108, 629); and ratio, 285.6 (32.2, 758.5) versus 6.1 (2.3, 20.3) (all p <
      0.0001). Higher sFlt1/PlGF ratio correlated negatively with timing of delivery (r
      = -0.60, p < 0.001) and the risk of adverse outcomes was markedly elevated among
      women in highest tertile compared with lower tertile (odds ratio, 14.77; 95%
      confidence interval (CI), 4.28-51.00). The addition of sFlt1/PlGF ratio (>=85) to
      hypertension and proteinuria significantly improved the prediction for subsequent
      adverse outcomes (AUC 0.89 (95% CI): 0.82, 0.95) for hypertension, proteinuria,
      and sFlt1/PlGF (AUC = 0.75 (0.65, 0.85)) for hypertension alone (p = 0.002).
      Compared with normative controls, women who were evaluated for preeclampsia
      without adverse outcomes had higher MoM for sFlt1/PlGF ratio; these values were
      further elevated in women with adverse outcomes. sFlt1/PlGF ratios measured on
      the KRYPTOR platform were highly correlated with measurements obtained using
      Elecys platform (r = 0.97, p < 0.001). CONCLUSIONS: In women with suspected
      preeclampsia presenting prior to 34 weeks of gestation, KRYPTOR assays for
      circulating sFlt1 and PlGF when used in conjunction with standard clinical
      evaluation performs well in the prediction of adverse maternal and perinatal
      outcomes occurring within 2 weeks of presentation.

PMID- 27028797
TI  - Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese
      patients unveiled by an integrated meta-omics-based approach.
AB  - : There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by
      gut microbiota. Therefore, we investigated its modifications in pediatric NAFLD
      patients using targeted metagenomics and metabolomics. Stools were collected from
      61 consecutive patients diagnosed with nonalcoholic fatty liver (NAFL),
      nonalcoholic steatohepatitis (NASH), or obesity and 54 healthy controls (CTRLs),
      matched in a case-control fashion. Operational taxonomic units were pyrosequenced
      targeting 16S ribosomal RNA and volatile organic compounds determined by solid
      phase microextraction gas chromatography-mass spectrometry. The alpha-diversity
      was highest in CTRLs, followed by obese, NASH, and NAFL patients; and beta
      diversity distinguished between patients and CTRLs but not NAFL and NASH.
      Compared to CTRLs, in NAFLD patients Actinobacteria were significantly increased
      and Bacteroidetes reduced. There were no significant differences among the NAFL,
      NASH, and obese groups. Overall NAFLD patients had increased levels of
      Bradyrhizobium, Anaerococcus, Peptoniphilus, Propionibacterium acnes, Dorea, and
      Ruminococcus and reduced proportions of Oscillospira and Rikenellaceae compared
      to CTRLs. After reducing metagenomics and metabolomics data dimensionality,
      multivariate analyses indicated a decrease of Oscillospira in NAFL and NASH
      groups and increases of Ruminococcus, Blautia, and Dorea in NASH patients
      compared to CTRLs. Of the 292 volatile organic compounds, 26 were up-regulated
      and 2 down-regulated in NAFLD patients. Multivariate analyses found that
      combination of Oscillospira, Rickenellaceae, Parabacteroides, Bacteroides
      fragilis, Sutterella, Lachnospiraceae, 4-methyl-2-pentanone, 1-butanol, and 2
      butanone could discriminate NAFLD patients from CTRLs. Univariate analyses found
      significantly lower levels of Oscillospira and higher levels of 1-pentanol and 2
      butanone in NAFL patients compared to CTRLs. In NASH, lower levels of
      Oscillospira were associated with higher abundance of Dorea and Ruminococcus and
      higher levels of 2-butanone and 4-methyl-2-pentanone compared to CTRLs.
      CONCLUSION: An Oscillospira decrease coupled to a 2-butanone up-regulation and
      increases in Ruminococcus and Dorea were identified as gut microbiota signatures
      of NAFL onset and NAFL-NASH progression, respectively. (Hepatology 2017;65:451
      464).

PMID- 27028796
TI  - Influence of initial angiotensin receptor blockers on treatment persistence in
      uncomplicated hypertension: A nation-wide population-based study.
AB  - We identified 55 504 uncomplicated, treatment-naive hypertensive patients who
      started angiotensin II receptor blockers (ARBs) in 2012 from national claims
      data. The proportion of patients remaining on any hypertension treatment at 12
      months and the adherence rate were similar between the losartan cohort (66.82%
      and 68.25%) and the nonlosartan ARB cohort (67.48% and 69.01%). After adjusting
      for confounding factors, there was no difference in persistence (aHR 0.98, 95%
      confidence interval (CI) 0.95-1.01) on hypertension treatment between losartan
      and nonlosartan ARB cohort. Post hoc analysis showed that patients initially
      prescribed eprosartan, irbesartan (both, aHR 1.33), and telmisartan (aHR 1.11)
      were more likely to discontinue the initial drug, whereas valsartan initiators
      (aHR 0.96) were less likely compared with losartan initiators. 

PMID- 27028798
TI  - Healthcare Coinsurance Elasticity Coefficient Estimation Using Monthly Cross
      sectional, Time-series Claims Data.
AB  - Published estimates of the healthcare coinsurance elasticity coefficient have
      typically relied on annual observations of individual healthcare expenditures
      even though health plan membership and expenditures are traditionally reported in
      monthly units and several studies have stressed the need for demand models to
      recognize the episodic nature of healthcare. Summing individual healthcare
      expenditures into annual observations complicates two common challenges of
      statistical inference, heteroscedasticity, and regressor endogeneity. This paper
      estimates the elasticity coefficient using a monthly panel data model that
      addresses the heteroscedasticity and endogeneity problems with relative ease.
      Healthcare claims data from employees of King County, Washington, during 2005 to
      2011 were used to estimate the mean point elasticity coefficient: -0.314 (0.015
      standard error) to -0.145 (0.015 standard error) depending on model
      specification. These estimates bracket the -0.2 point estimate (range: -0.22 to 
      0.17) derived from the famous Rand Health Insurance Experiment. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27028799
TI  - Developing a Registry for Thyroid Incidentalomas: Lessons Learned and the Path
      Forward.
AB  - BACKGROUND: Incidentalomas are findings on an imaging test done for other
      reasons, for which there are no matching symptoms in the patient. They are common
      in the adrenal gland, pancreas, liver, and thyroid, among other sites.
      Incidentalomas are a problem because we have a limited understanding of their
      natural history: it is difficult to know how much of a threat they pose to
      individual patients. An observational registry that would allow a systematic
      study of thyroid incidentalomas could reveal their natural history and the effect
      of detection on patients' lives, as well as document the cost to the healthcare
      system. A registry would help to determine which incidentalomas could be
      monitored and which require action. STUDY DESIGN: A cohort study was conducted,
      with case identification via radiology imaging reports with follow-up through a
      minimum of one year post-identification. RESULTS: In one year, >109,000 imaging
      studies were performed that might reveal an incidental thyroid finding (computed
      tomography scans of the neck or chest, magnetic resonance imaging of the neck,
      plain x-ray of the chest, non-thyroid directed ultrasound of the neck, positron
      emission tomography scan, or myocardial perfusion scan). A total of 125 patients
      were identified as having a thyroid nodule, with a <1% reporting rate among
      eligible imaging studies, much lower than other published estimates of incidental
      thyroid nodule prevalence on imaging. Of the 125 nodules, 46 had been previously
      identified (were not "new"). Of the 79 patients with new nodules, more than half
      (44; 53%) were not notified of the finding. The approved study design allowed
      contact only with those who had been clearly notified of their thyroid nodule.
      Among those who could be reached, many did not recall the finding (6/15; 40%). Of
      those who did recall the finding, none self-identified it as an incidentaloma.
      CONCLUSIONS: There are serious logistical and ethical hurdles to developing
      observational registries of incidentalomas, as well as threats to data validity
      because incidentalomas are incompletely identified, reported, and acted upon.
      Solutions commonly used to optimize data quality for registries would increase
      reporting, but could potentially overwhelm the healthcare system and harm
      patients. A novel interventional design that is proposed here for future work may
      facilitate both study and amelioration of the problem.

PMID- 27028800
TI  - Therapeutic Potential of Resveratrol in Lymphoid Malignancies.
AB  - Natural products have always been sought as a dependable source for the cure of
      many fatal diseases including cancer. Resveratrol (RSV), a naturally occurring
      plant polyphenol, has been of recent research interest and is being investigated
      for its beneficial biological properties that include antioxidant, anti
      inflammatory, proapoptotic, and growth inhibitory activities. These effects are
      mainly mediated by cell cycle arrest, upregulation of proapoptotic proteins, loss
      of mitochondrial potential, and generation of reactive oxygen species. Among the
      beneficial properties of RSV, the anticancer property has been of the prime focus
      and extensively explored during the last few years. Although reports exist on the
      chemopreventive role of RSV in many solid tumors, limited information is
      available on the antiproliferative activity of RSV in human lymphoma cells and
      experimental models. Potential mechanisms for its antiproliferative effect
      include induction of cell differentiation, apoptosis, and inhibition of DNA
      synthesis. In this review, the different kinds of lymphoid malignancies and the
      main mechanisms of cell death induced by resveratrol are discussed. The
      challenges are limiting in vivo experimental studies involving resveratrol. An
      attempt for the translation of this compound into a clinical drug also forms a
      part of this review. 

PMID- 27028802
TI  - Time to focus on implementation: the need to re-orient research on physical
      activity in childcare services.

PMID- 27028801
TI  - Divergent in vivo activity of non-serotonergic and serotonergic VGluT3-neurones
      in the median raphe region.
AB  - KEY POINTS: The median raphe is a key subcortical modulatory centre involved in
      several brain functions, such as regulation of the sleep-wake cycle, emotions and
      memory storage. A large proportion of median raphe neurones are glutamatergic and
      implement a radically different mode of communication compared to serotonergic
      cells, although their in vivo activity is unknown. We provide the first
      description of the in vivo, brain state-dependent firing properties of median
      raphe glutamatergic neurones identified by immunopositivity for the vesicular
      glutamate transporter type 3 (VGluT3) and serotonin (5-HT). Glutamatergic
      populations (VGluT3+/5-HT- and VGluT3+/5-HT+) were compared with the purely
      serotonergic (VGluT3-/5-HT+ and VGluT3-/5-HT-) neurones. VGluT3+/5-HT+ neurones
      fired similar to VGluT3-/5-HT+ cells, whereas they significantly diverged from
      the VGluT3+/5-HT- population. Activity of the latter subgroup resembled the
      spiking of VGluT3-/5-HT- cells, except for their diverging response to sensory
      stimulation. The VGluT3+ population of the median raphe may broadcast rapidly
      varying signals on top of a state-dependent, tonic modulation. ABSTRACT:
      Subcortical modulation is crucial for information processing in the cerebral
      cortex. Besides the canonical neuromodulators, glutamate has recently been
      identified as a key cotransmitter of numerous monoaminergic projections. In the
      median raphe, a pure glutamatergic neurone population projecting to limbic areas
      was also discovered with a possibly novel, yet undetermined function. In the
      present study, we report the first functional description of the vesicular
      glutamate transporter type 3 (VGluT3)-expressing median raphe neurones. Because
      there is no appropriate genetic marker for the separation of serotonergic (5-HT+)
      and non-serotonergic (5-HT-) VGluT3+ neurones, we utilized immunohistochemistry
      after recording and juxtacellular labelling in anaesthetized rats. VGluT3+/5-HT-
      neurones fired faster, more variably and were permanently activated during
      sensory stimulation, as opposed to the transient response of the slow firing
      VGluT3-/5-HT+ subgroup. VGluT3+/5-HT- cells were also more active during
      hippocampal theta. In addition, the VGluT3-/5-HT- population, comprising putative
      GABAergic cells, resembled the firing of VGluT3+/5-HT- neurones but without any
      significant reaction to the sensory stimulus. Interestingly, the VGluT3+/5-HT+
      group, spiking slower than the VGluT3+/5-HT- population, exhibited a mixed
      response (i.e. the initial transient activation was followed by a sustained
      elevation of firing). Phase coupling to hippocampal and prefrontal slow
      oscillations was found in VGluT3+/5-HT- neurones, also differentiating them from
      the VGluT3+/5-HT+ subpopulation. Taken together, glutamatergic neurones in the
      median raphe may implement multiple, highly divergent forms of modulation in
      parallel: a slow, tonic mode interrupted by sensory-evoked rapid transients, as
      well as a fast one capable of conveying complex patterns influenced by sensory
      inputs.

PMID- 27028803
TI  - Be Healthy as a Fish Educational Program at the International Institute of
      Molecular and Cell Biology in Warsaw, Poland.
AB  - The purpose of the Be Healthy as a Fish educational program that is organized by
      the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw,
      Poland, is to educate children about the ways in which zebrafish can be used as a
      model organism to help scientists understand the way the human body works. We
      introduce Be Healthy as a Fish workshops to children in fourth to sixth grades of
      primary school (9-11 years old), together with two kinds of materials under the
      same title: a book and a movie. We focus on the field of biology in a way that
      complements the children's classroom curriculum and encourages them to broaden
      their interests in biology in the future. The Be Healthy as a Fish educational
      program was inaugurated in 2014 at the Warsaw Science Festival. As of October 31,
      2015, 526 primary school students participated in 27 workshops. Approximately
      2000 people have received the book and nearly 1700 people have watched the movie.
      Be Healthy as a Fish: Origin of the Title There is a popular saying in Poland
      that someone is "healthy as a fish" meaning that one enjoys good health. Does
      this imply that fish are really that healthy? Obviously, some fish may not be
      healthy. Just like other animals and humans, they can and do get sick. However,
      this common and deceptive impression of "healthy fish" results from the fact that
      people hardly ever have an opportunity to observe a fish that is sick. Why does
      our educational program have such a possibly misleading title that may not always
      be true? We took advantage of this provocative title and commonly known
      expression and assigned to it a completely new meaning: fish can get sick, but
      they are important for human health. Notably, this catchy sentence intrinsically
      combines two keywords-health and fish-which, in our opinion, makes it a good
      title for a successful educational program.

PMID- 27028804
TI  - A Chemically Cross-Linked NbO-Type Metal-Organic Framework: Cage or Window
      Partition?
AB  - By using a presynthetically cross-linked octacarboxylate ligand, a chemically
      cross-linked version of the NbO-type metal-organic framework (MOF) NOTT-101 (ZJNU
      80) was prepared. Single-crystal X-ray structure analysis showed that ZJNU-80
      adopts the same topology as the parent compound NOTT-101, and the tethering
      groups take part in the window partition, not the cage partition. The gas
      adsorption studies showed that, despite the lower porosity, ZJNU-80a exhibits low
      pressure gas adsorption behavior similar to that of the parent MOF NOTT-101a
      toward CO2, CH4, and N2 at ambient temperature because of the fact that the
      window partition as a result of chemical cross-linking does not almost alter the
      pore-size distributions. However, different adsorption behaviors toward 1-butene,
      a molecule with even larger kinetic diameter than that of the aforementioned
      adsorbates, were observed because the window partition alters the efficiency with
      which 1-butene molecules pack within ZJNU-80a and NOTT-101a at conditions close
      to saturation. This work provides a fundamental understanding on the effect of
      chemical cross-linking on the MOF's structure and gas adsorption properties. 

PMID- 27028805
TI  - Focal liver lesions found incidentally.
AB  - Incidentally found focal liver lesions are a common finding and a reason for
      referral to hepatobiliary service. They are often discovered in patients with
      history of liver cirrhosis, colorectal cancer, incidentally during work up for
      abdominal pain or in a trauma setting. Specific points should considered during
      history taking such as risk factors of liver cirrhosis; hepatitis, alcohol
      consumption, substance exposure or use of oral contraceptive pills and metabolic
      syndromes. Full blood count, liver function test and tumor markers can act as a
      guide to minimize the differential diagnosis and to categorize the degree of
      liver disease. Imaging should start with B-mode ultrasound. If available,
      contrast enhanced ultrasound is a feasible, safe, cost effective option and
      increases the ability to reach a diagnosis. Contrast enhanced computed tomography
      should be considered next. It is more accurate in diagnosis and better to study
      anatomy for possible operation. Contrast enhanced magnetic resonance is the gold
      standard with the highest sensitivity. If doubt still remains, the options are
      biopsy or surgical excision. 

PMID- 27028806
TI  - [Advances in Molecular Cloning].
AB  - "Molecular cloning" meaning creation of recombinant DNA molecules has impelled
      advancement throughout life sciences. DNA manipulation has become easy due to
      powerful tools showing exponential growth in applications and sophistication of
      recombinant DNA technology. Cloning genes has become simple what led to an
      explosion in the understanding of gene function by seamlessly stitching together
      multiple DNA fragments or by the use of swappable gene cassettes, maximizing
      swiftness and litheness. A novel archetype might materialize in the near future
      with synthetic biology techniques that will facilitate quicker assembly and
      iteration of DNA clones, accelerating the progress of gene therapy vectors,
      recombinant protein production processes and new vaccines by in vitro chemical
      synthesis of any in silico-specified DNA construct. The advent of innovative
      cloning techniques has opened the door to more refined applications such as
      identification and mapping of epigenetic modifications and high-throughput
      assembly of combinatorial libraries. In this review, we will examine the major
      breakthroughs in cloning techniques and their applications in various areas of
      biological research that have evolved mainly due to easy construction of novel
      expression systems.

PMID- 27028807
TI  - [Progestins and Carcinogenesis].
AB  - Progesterone and its analogs may exert opposite effects on cell proliferation,
      apoptosis, and epithelial-mesenchymal transition, leading to higher cell motility
      and metastasis. Their ultimate effect is determined by a number of factors: the
      structure and concentration of the steroid, its affinity for various forms of
      steroid hormone receptors, activation of nongenomic mechanisms, the composition
      and proportion of different progesterone receptors and sensors, activity of
      various signaling pathways, the set of transcription factor coregulators, DNA
      accessibility in chromatin, activity of steroid-metabolizing enzymes,
      intercellular interactions within tissues, the hormonal status of the body,
      disease stage, and species-specific features. The review considers the factors
      that determine the role progestins play in proliferation and apoptosis of human
      tumor cells of various origins.

PMID- 27028808
TI  - [The Biological Function of SHP2 in Human Disease].
AB  - Tyrosyl phosphorylation participates in various pathological and physiological
      processes, which are regulated by protein tyrosine kinases (PTKs) and protein
      tyrosine phosphatases (PTPs). The Src homology-2 domain containing phosphatase
      SHP2 (encoded by PTPN11) is an important phosphatase, which was found to be
      implicated in the regulation of genetic disease, development, metabolic,
      neurological, muscle, skeletal disease and cancer. Germline mutations in PTPN11
      cause the Noonan Syndrome, LEOPARD syndrome and metachondromatosis. Somatic
      PTPN11 mutations occur in hematologic malignancies and in solid tumors. SHP2 is
      also an important component in oncogenic signaling pathways. It may play
      different roles in different stages and positions of human cancers. Whether SHP2
      is an oncogene or cancer suppressor gene remains to be elucidated. Elucidation of
      the regulatory mechanisms of SHP2 in human disease will provide new insights into
      disease and new targets for therapy. Here, we summarized the structural basis and
      recent research progression on SHP2 in various human disease, including genetic
      and cancer diseases.

PMID- 27028809
TI  - [Hormone Resistance and Neuroendocrine Differentiation Due to Accumulation of
      Genetic Lesions during Clonal Evolution of Prostate Cancer].
AB  - Progression of malignant tumors is largely due to clonal evolution of the primary
      tumor, clones acquiring different sets of molecular genetic lesions. Lesions can
      confer a selective advantage in proliferation rate or metastasis on the tumor
      cell population, especially if developing resistance to anticancer therapy.
      Prostate cancer (PCa) provides an illustrative example of clinically significant
      clonal evolution. The review considers the genetic alterations that occur in
      primary PCa and the mechanism whereby hormone-refractory PCa develops on hormone
      therapy, including mutations and alternative splicing of the androgen receptor
      gene (AR) and intratumoral androgen synthesis. Certain molecular genetic lesions
      determine resistance to new generation inhibitors (AR mutations that block the
      antagonist effect or allow other hormones to activate the receptor) or lead to
      neuroendocrine differentiation (repression of the AR signaling pathway, TP53
      mutations, and amplification of the AURKA or MYCN oncogene). Multistep therapy
      based on the data about somatic mutations associated with progression and
      metastasis of the primary tumor can be expected to significantly improve the
      survival of patients with advanced PCa in the nearest future.

PMID- 27028810
TI  - [Methods to Biosynthesize Mammalian Selenocysteine-Containing Proteins in vitro].
AB  - The main problem in studying mammalian selenocysteine-containing proteins is that
      the proteins are difficult to obtain in a recombinant form because the amino acid
      selenocysteine (Sec), which is their component, is encoded by TGA, which is one
      of the stop codons. When only the open reading frame of a target protein is
      cloned in a plasmid, translation is prematurely terminated at the TGA codon. An
      intricate natural mechanism allows the codon to be recognized as a selenocysteine
      codon and involves various cis- and trans-acting factors, such as the
      selenocysteine insertion sequence (SECIS), mRNA secondary structure,
      selenocysteine tRNA Sec-tRNA^( [Ser]Sec), SECIS-binding protein 2 (SBP2),
      selenocysteine-specific elongation factor EFsec, and others. Generation of
      recombinant selenoproteins in preparative amounts directly depends on the
      expression levels of the cis- and trans-acting transcription and translation
      factors to further complicate the problem, and cysteine homologs of
      selenoproteins are consequently used in many studies. Several methods designed to
      express mammalian selenoproteins in vitro are considered in the review.

PMID- 27028811
TI  - [Induction of Unspecific Permeabilization of Mitochondrial Membrane and Its Role
      in Cell Death].
AB  - Mitochondria participate in various vital cellular processes. Violation of their
      functions can lead to the development of cardiovascular and neurodegenerative
      diseases and malignancies. One of the key events responsible for mitochondrial
      damage-induction of Ca^(2+)-dependent mitochondrial permeability transition, due
      to the opening of a nonspecific pore in the inner mitochondrial membrane. Despite
      active studies of pore components, its detailed structure has not yet been
      established. This review analyzes possible constituents and regulators of the
      pore, the role of the pore in various pathologies, and hypotheses that explain
      the organization of the pores. Elucidation of these questions can help developing
      strategies for the treatment of a wide range of pathologies-from Alzheimer and
      Parkinson's disease to cancer.

PMID- 27028812
TI  - [Role of PDLIM4 and c-Src in Breast Cancer Progression].
AB  - High heterogeneity is characteristic of oncology diseases, often complicating the
      choice of optimal anticancer treatment. One cancer type may combine tumors
      differing in histogenesis, genetic lesions, and mechanism of cell transformation.
      Differences in the mechanism of cell malignant transformation result in specifics
      of cancer cell metabolism and sensitivity to various agents, including anticancer
      treatments. Hence, the molecular subtype of a tumor is essential to know for
      choosing the optimal therapeutic strategy. The review considers the role actin
      associated proteins and tyrosine kinases, in particular, PDLIM4 and Src kinase,
      play in the formation of pathological signaling pathways.

PMID- 27028813
TI  - [piRNAs: Biology and Bioinformatics].
AB  - The discovery of small noncoding RNAs and their roles in a variety of regulatory
      mechanisms have led many scientists to look at the principles of functioning of
      the cells on a completely different side. Small RNA molecules play key roles in
      important processes such as the co- and posttranscriptional regulation of gene
      expression, epigenetic modification of DNA and histones and antiviral protection.
      piRNA is one of the most numerous, although the least-studied class of small
      noncoding RNAs. piRNA is highly expressed in the germ line of most eukaryotes and
      its main function is to regulate the activity of mobile elements during embryonic
      development. Moreover, recent studies reveal moderate activity of piRNA in
      somatic cells. However, the mechanisms of piRNA biogenesis and function are still
      poorly understood and are the object of intensive researches. This review
      presents actual information about the biogenesis and various functions of piRNA,
      as well as bioinformatical aspects of this field of molecular biology.

PMID- 27028814
TI  - [Evaluation of GPx1 Pro198Leu Polymorphism in Idiopathic Male Infertility].
AB  - Infertility is defined as failure to conceive a child after 1 year of unprotected
      regular sexual intercourse. Approximately half of all cases of infertility are
      caused by factors related to the male. In nearly 50% of infertile men it is not
      possible to determine the cause of infertility and this situation has been
      defined as unexplained or idiopathic. Oxidative stress plays an important role in
      the pathophysiology of male infertility. Oxidative stress results from an
      imbalance in free radicals and antioxidant defense mechanisms of the body.
      Genetic variations in the antioxidant gene coding for GPx enzyme may lead to
      decreased or impaired regulation of its enzymatic activity and alter reactive
      oxygen species (ROS) detoxification. We have investigated the possible
      association between polymorphism GPx1 Pro198Leu and idiopathic male infertility.
      One hundred patients with idiopathic male infertility and one hundred fifty
      healthy volunteers were enrolled. Genomic DNA was extracted from blood samples.
      Genotyping for the GPx1 Pro198Leu polymorphism was done by PCR-restriction
      fragment length polymorphism (RFLP) using ApaI. The genotype frequencies were 11%
      (Leu/Leu), 76% (Pro/Leu) and 13% (Pro/Pro) in the patient group and 8.7%
      (Leu/Leu), 67.3% (Pro/Leu) and 24% (Pro/Pro) in the control group. The genotype
      and allele frequencies of GPx1 Pro198Leu did not differ between the patient group
      and the control group (P = 0.09 and P = 0.1, respectively). In conclusion, there
      is no correlation between idiopathic male infertility and the GPx1 codon
      Pro198Leu polymorphism. Further studies are needed to investigate other genetic
      factors that influence the development of idiopathic male infertility.

PMID- 27028815
TI  - [Genes for Fibrogenesis in the Determination of Susceptibility to Myocardial
      Infarction].
AB  - A group of patients with ischemic heart disease and myocardial infarction (N =
      156) and a reference population sample (N = 300) were genotyped for 58 single
      nucleotide polymorphisms (SNPs) in the genes involved in extracellular matrix
      function and collagen metabolism or associated with cardiovascular diseases and
      atherosclerotic plaque stability. Genotyping was performed by mass-spectrometry
      with two multiplex sets of 27 and 31 SNPs. The study revealed different genetic
      composition of predisposition to cardiovascular disease continuum (CVDC) syntropy
      (patients with concomitant conditions: hypercholesterolemia, hypertension, and
      type-II diabetes mellitus, N = 96) and to isolated myocardial infarction (without
      these conditions, N = 60). Only the KIAA1462 gene (rs3739998) showed associations
      with both CVDC syntropy (OR = 1.71; 95% CI 1.19-2.45; r = 0.003) and isolated
      infarction (OR = 1.58; 95% CI 1.05-2.40; r = 0.028). Isolated myocardial
      infarction was also associated with LIG1 (rs20579) (OR = 2.08; 95% CI 1.06-4.17;
      r = 0.028) and ADAMDEC1 (rs3765124) (OR = 1.63; 95% CI 1.07-2.50; r = 0.020).
      CVDC syntropy was associated with CDKN2BAS1 (rs1333049) (OR = 1.48; 95% CI 1.03
      2.12; r = 0.029) and APOA2 (rs5082) (OR = 1.47; 95% CI 1.02-2.11; r = 0.035). So,
      genes involved in fibrogenesis contribute to predisposition to the myocardial
      infarction as well. Isolated myocardial infarction and CVDC syntropy can be
      considered as pathogenetically different cardiovascular conditions, with
      different genes that contribute to the susceptibility.

PMID- 27028816
TI  - [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory
      Gene in Xenopus laevis].
AB  - Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative
      anion channel-related proteins with diverse physiological functions. Exploring
      CLCA diversity is important for prediction of gene structure and function. In an
      effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and
      characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. Cloning
      of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA
      ends (RACE), and a tissue distribution analysis by semi-quantitative reverse
      transcription (RT) PCR or real-time PCR. We obtained a 2958 bp xCLCA3 cDNA
      sequence with an open reading frame encoding 943 amino acids. According to the
      primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple
      sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein
      kinase II phosphorylation sites, five putative hydrophobic segments, and the
      HExxH metalloprotease motif. Additionally, the transmembrane prediction server
      yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A
      domain with one transmembrane domain in the C-terminal region. Expression
      analysis showed that xCLCA3 is expressed in a number of tissues, with strong
      expression in the brain, colon, small intestine, lung, kidney, and spleen, and
      poor expression in the heart and liver. These results suggest that xCLCA3 may be
      a candidate CLCA family member as well as a metalloprotease, rather than just an
      ion channel accessory protein.

PMID- 27028817
TI  - [Validation of the Antiproliferative Effects of Euphorbia tirucalli Extracts in
      Breast Cancer Cell Lines].
AB  - Medicinal plant extracts have recently attracted attention of modern medical
      science research due to their non-lethal activity. Currently, up to 50% of the
      world drugs including chemotherapeutic drugs such as taxol and camptothecin are
      derived from natural products. Euphorbia tirucalli has a long history of usage as
      traditional medicine in Africa and has been widely used in the treatment of
      different cancers. In this study, we explore the medical properties of E.
      tirucalli extracts in breast cancer development. To achieve this, stems of E.
      tirucalli were dried, crushed and extracted with butanol, hexane or methanol
      (based on 1 g of dry substance in 10 mL of a solvent). The dried extracts were re
      dissolved in DMSO and investigated. Composition of each extract was analyzed
      using liquid chromatography-mass spectroscopy (LC-MS). Extracts were found to
      contain different types of secondary metabolites mainly terpenes and flavonoids.
      Breast cancer cell lines (MCF-7 and MDA-MB 231) were treated with various
      concentrations of the extracts for up to 48 h. Cell viability, cell cycle,
      apoptosis and gene expression were analysed. In cells, extracts were found to
      inhibit cell proliferation in a concentration and cell type dependent manner.
      Analysis of the cause of antiproliferation revealed that most cells were arrested
      at the G0/G1 phase by p21 overexpression. In general, most pro-apoptotic genes
      like Bax and caspase-8 were significantly up-regulated in cells treated with
      plant extracts. These results suggest that the extracts might induce cell cycle
      arrest at G0/G1 with p21 attributing to this molecular mechanism.

PMID- 27028818
TI  - [Increase in GP IIb-IIIa and P2Y12 Receptors in Activated Platelets as the
      Possible Indicator of de novo Protein Synthesis].
AB  - Although platelets lack nuclei, they are capable of de novo protein synthesis. We
      speculate that key platelet receptors are involved in the regulation of this
      process, and the changes in their number indicate the de novo protein synthesis
      in platelets. The object of our study was native platelets obtained from healthy
      donors. Using flow cytometry and Western blot, we determined the number of GP IIb
      IIIa receptors (fibrinogen receptor) and P2Y12 receptors (ADP receptor) on the
      surface of platelets upon their activation with ADP and collagen. To verify the
      approaches and techniques used, we studied IL-1beta protein, which was previously
      shown to be synthesized de novo in activated platelets. GP IIb-IIIa receptor
      numbers correlate with the number of P2Y12 receptors on the cell surface (R =
      0.45, p = 0.03). It was demonstrated that the platelet receptor numbers are
      higher on the surface of the cells with high functional activity. According to
      the data obtained by Western blot, upon the cell activation with ADP, the number
      of GP IIb-IIIa and P2Y12 receptors increases, which may serve as evidence of
      these proteins being synthesized in the activated platelets. It was observed that
      the level of P2Y12 and IL-1beta was lower in the samples where GP IIb-IIIa
      receptor was blocked by the selective inhibitor, i.e., the Fab fragment of the
      antibodies that specifically recognizes the GP IIb-IIIa complex. This suggests
      the important role of GP IIb-IIIa receptor in the regulation of protein
      synthesis.

PMID- 27028819
TI  - [The Role of Calcium in the Conformational Changes of the Recombinant
      S100A8/S100A9].
AB  - Calprotectin is a member of the EF-hand proteins, composed of two subunits,
      S100A8 (MRP8) and S100A9 (MRP14). These proteins are involved in important
      processes including cell signaling, regulation of inflammatory responses, cell
      cycle control, differentiation, regulation of ion channel activity and defense
      against microbial agents in a calcium dependent manner. In the present study,
      recombinant S100A8 and S100A9 were expressed in E. coli BL21 and then purified
      using Ni-NTA affinity chromatography. The structure of the S100A8/A9 complex in
      the presence and absence of calcium was assessed by circular dichroism and
      fluorescence spectroscopy. The intrinsic fluorescence emission spectra of the
      S100A8/A9 complex in the presence of calcium showed a reduction in fluorescence
      intensity, reflecting conformational changes within the protein with the exposure
      of aromatic residues to the protein surface. The far ultraviolet-circular
      dichroism spectra of the complex in the presence of calcium revealed minor
      changes in the regular secondary structure of the complex. Also, increased
      thermal stability of the S100A8/A9 complex in the presence of calcium was
      indicated.

PMID- 27028820
TI  - [Identification of the Disease-Associated Genes in Periodontitis Using the Co
      expression Network].
AB  - The aim of this study was to investigate the disease-associated genes in
      periodontitis. In the present experiments, the topological analysis of the
      differential co-expression network was proposed. Using the GSE16134 dataset
      downloaded from the European Molecular Biology Laboratory-European Bioinformatics
      Institute, a co-expression network was constructed after the differentially
      expressed genes (DEGs) were identified between the diseased (242 samples) and
      healthy (69 samples) gingival tissues from periodontitis patients. The
      topological properties of the modules obtained from the network as well as an
      analysis of transcription factors (TFs) were used to determine the disease
      associated genes. The gene ontology and pathway enrichment analysis was performed
      to investigate the underlying mechanisms of these disease related genes. A total
      of 524 DEGs, including 19 TFs were identified and a co-expression network with
      2569 edges was obtained. Among the 7 modules gained in the network, the TFs
      (ZNF215, ZEN273, NFAT5, TRPS1, MEF2C and FLI1) were considered to be important in
      periodontitis. The functional and pathway enrichment analysis revealed that the
      DEGs were highly involved in the immune system. The co-expression network
      analysis and TFs identified in periodontitis may provide opportunities for
      biomarker development and novel insights into the therapeutics of periodontitis.

PMID- 27028821
TI  - [GH10 Family of Glycoside Hydrolases: Structure and Evolutionary Connections].
AB  - Evolutionary connections were analyzed for endo-beta-xylanases, which possess the
      GH10 family catalytic domains. A homology search yielded thrice as many proteins
      as are available from the Carbohydrate-Active Enzymes (CAZy) database. Lateral
      gene transfer was shown to play an important role in evolution of bacterial
      proteins of the family, especially in the phyla Acidobacteria, Cyanobacteria,
      Planctomycetes, Spirochaetes, and Verrucomicrobia. In the case of
      Verrucomicrobia, 23 lateral transfers from organisms of other phyla were
      detected. Evolutionary relationships were observed between the GH10 family
      domains and domains with the TIM-barrel tertiary structure from several other
      glycosidase families. The GH39 family of glycoside hydrolases showed the closest
      relationship. Unclassified homologs were grouped into 12 novel families of
      putative glycoside hydrolases (GHL51-GHL62).

PMID- 27028822
TI  - [Hypothetical SNP Markers That Significantly Affect the Affinity of the TATA
      Binding Protein to VEGFA, ERBB2, IGF1R, FLT1, KDR, and MET Oncogene Promoters as
      Chemotherapy Targets].
AB  - The following hypothesis has been proposed: IF an SNP can significantly increase
      the expression of an oncogene by increasing the affinity of the TATA-binding
      protein (TBP) to its promoter, THEN this SNP can also reduce the apparent
      bioactivity of inhibitors of this oncogene during antitumor chemotherapy and vice
      versa. In the context of this hypothesis, the previously proposed method
      (http://beehive.bionet.nsc. ru/cgi-bin/mgs/tatascan/start.pl) was applied to
      analyze all SNPs found within the [-70; -20] regions (which harbor all proven TBP
      binding sites) of the promoters of VEGFA, EGFR, ERBB2, IGF1R, FLT1, KDR, and MET
      oncogenes according to the human reference genome, hg19. For 83% of these SNPs,
      their effect on TBP affinity to the oncogene promoters required for assembly of
      preinitiation complexes was not significant. rs36208385, rs36208384, rs370995111,
      rs372731987, rs111811434, rs369547510, rs76407893, rs369728300, and rs72001900
      can potentially serve as SNP markers to reduce the apparent bioactivity of
      oncogene inhibitors, while rs141092704, rs184083669, rs145139616, rs200697953,
      rs187746433, rs199730913, rs377370642, rs114484350, rs374921120, rs146790957,
      rs376727645, and rs72001900 can be the markers for enhancing this activity.

PMID- 27028823
TI  - [Alpha-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line
      (HCT116)].
AB  - Alpha-1-antitrypsin (AAT), an acute phase protein, is the principal circulatory
      anti-protease. This multifunctional protein is encoded by the SERPINA1 gene.
      Although AAT was recognised as a potential tumour marker, its role in cancer
      biology remains unknown. Given that it has been demonstrated that AAT has an anti
      apoptotic property against non-malignant cells, we aimed to investigate whether
      AAT affects apoptosis in a colon cancer cell line (HCT116). The presence of AAT
      in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2,
      PI3K/Akt pathways as well as NF-kappaB. The dominantly recovered cell viability
      was observed in the co-treatment with MEK1/2 inhibitor U0126. In addition, it was
      revealed that AAT almost completely abolished U0126-induced apoptosis through
      maintenance of the autophagy process. Our study revealed for the first time that
      the observed cyto-protection triggered by AAT was accompanied by sustained
      autophagy which opposed apoptosis. These results may contribute to understanding
      of the role of AAT in cancer development and evaluation of efficacy of cancer
      therapy.

PMID- 27028824
TI  - [New Class of Sfr1 Protein Repeats Essential for Homologous Recombination in
      Schizosaccharomyces pombe Yeast in Mitosis].

PMID- 27028825
TI  - [Changes in the Expression of Dopaminergic Genes in Brain Structures of Male Mice
      Exposed to Chronic Social Defeat Stress: An RNA-seq Study].
AB  - Whole-transcriptome analysis (RNA-seq) has been used to analyze changes in the
      expression of dopaminergic genes that encode proteins involved in the synthesis,
      inactivation, and neurotransmission of dopamine in the striatum, ventral
      tegmental area, raphe nuclei of the midbrain, hypothalamus, and hippocampus of
      male mice subjected to chronic social defeat. The expression of Th, Ddc, and
      Slc6A3 (Dat1) was upregulated, while that of Ppp1r1b and Sncg was downregulated
      in the ventral tegmental area; the expression of Th, Ddc, Drd2, and Sncg was
      downregulated in the raphe nuclei of midbrain; the expression of Th, Aldh2, and
      Ppp1r1b was upregulated, while that of Maoa was downregulated in the
      hypothalamus; Drd1 and Snca expression was downregulated and that of Sncb was
      upregulated in the striatum, and Sncb expression was upregulated in the
      hippocampus. There were no statistically significant changes in the expression of
      Comt, Maob, Drd3, Drd4, or Drd5 in the brain areas analyzed in stressed male mice
      (compared to control animals). Thus, the number of differentially expressed
      dopaminergic genes and the direction of expression changes in male mice
      experiencing chronic stress are specific to regions of the brain. 

PMID- 27028826
TI  - [Downregulation of Human Adenovirus DNA Polymerase Gene by Modified siRNAs].
AB  - Human adenoviruses, in particular D8, D19, and D37, cause ocular infections.
      Currently, there is no available causally directed treatment, which efficiently
      counteracts adenoviral infectious diseases. In our previous work, we showed that
      gene silencing by means of RNA interference is an effective approach for
      downregulation of human species D adenoviruses replication. In this study, we
      compared the biological activity of siRNAs and their modified analogs targeting
      human species D adenoviruses DNA polymerase. We found that one of selectively 2'
      O-methyl modified siRNAs mediates stable and long-lasting suppression of the
      target gene (12 days post transfection). We suppose that this siRNA can be used
      as a potential therapeutic agent against human species D adenoviruses.

PMID- 27028833
TI  - Renoprotection.

PMID- 27028832
TI  - Placebo-controlled pilot trial testing dose titration and intravenous,
      intramuscular and subcutaneous routes for ketamine in depression.
AB  - OBJECTIVE: This pilot study assessed the feasibility, efficacy and safety of an
      individual dose-titration approach, and of the intravenous (IV), intramuscular
      (IM) and subcutaneous (SC) routes for treating depression with ketamine. METHOD:
      Fifteen treatment-refractory depressed participants received ketamine or
      midazolam (control treatment) in a multiple crossover, double-blind study.
      Ketamine was administered by IV (n = 4), IM (n = 5) or SC (n = 6) injection. Dose
      titration commenced at 0.1 mg/kg, increasing by 0.1 mg/kg up to 0.5 mg/kg, given
      in separate treatment sessions separated by >=1 week, with one placebo control
      treatment randomly inserted. Mood, psychotomimetic and hemodynamic effects were
      assessed and plasma ketamine concentrations assayed. RESULTS: Twelve participants
      achieved response and remission criteria, achieved at doses as low as 0.1 mg/kg.
      All three routes of administration resulted in comparable antidepressant effects.
      Fewest adverse effects were noted with the SC route. Antidepressant response,
      adverse effects and ketamine concentrations were dose-related. CONCLUSION:
      Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose
      titration approach is a practical method for optimizing the efficacy - side
      effects trade-off on an individual patient basis. This pilot study provides
      preliminary evidence for SC injection as a practical, feasible and efficacious
      treatment approach.

PMID- 27028835
TI  - Primary intra-articular sarcoma: a clinicopathological study of 15 cases.
AB  - AIMS: To assess the clinical and histopathological spectrum of primary intra
      articular sarcomas. METHODS AND RESULTS: Fifteen patients were identified as
      having primary intra-articular sarcomas and the clinical and pathological
      features were evaluated. There were nine males and six females who ranged in age
      from 16 to 84 (mean 44) years. All tumours originated in the knee joint. The
      pathological diagnoses included: five synovial sarcoma, three extraskeletal
      myxoid chondrosarcomas, two high-grade myxofibrosarcoma (one conventional, one
      epithelioid), two undifferentiated pleomorphic sarcoma (one with giant cells) and
      one each myxoinflammatory fibroblastic sarcoma, conventional hyaline
      chondrosarcoma, and high-grade myofibroblastic sarcoma. All tumours were treated
      by segmental resection or amputation. Adjuvant therapy was given in selected
      cases. Follow-up ranged from 11 to 150 months. Of patients with follow-up, two
      died of disease; one developed pulmonary metastases after 6 years and was then
      lost to follow-up. Nine patients were alive and free of disease 12-150 months
      after diagnosis. CONCLUSIONS: Primary sarcomas of the joints are very rare and
      most frequently affect the knee. Our experience indicates that synovial sarcoma
      and extraskeletal myxoid chondrosarcoma are the most common intra-articular
      sarcomas.

PMID- 27028834
TI  - Effects of local heat application before intravenous catheter insertion in
      chemotherapy patients.
AB  - AIMS AND OBJECTIVES: To characterise the effects of local heat application on the
      ease of subsequent intravenous catheter insertion. BACKGROUND: Intravenous
      catheter insertion is a challenging procedure for both nurses and chemotherapy
      patients. The local application of heat to the area before intravenous catheter
      insertion may decrease these difficulties by increasing venous distension and
      visibility. DESIGN: This study was an open label experimental study involving
      intervention and control groups. METHODS: Patients receiving chemotherapy were
      divided into intervention (n = 40) and control (n = 40) groups. For patients in
      the intervention group, a digital moist heating pad was applied to the arm
      prepared for catheter insertion for 10 minutes in addition to routine care. No
      additional preparation procedure beyond routine care was performed for control
      patients. Data were collected using a data collection form and evaluated using
      chi square, Fisher's exact chi square, Student's t, Mann-Whitney U, Wilcoxon and
      Pearson correlation tests. RESULTS: Local application of heat decreased patients'
      pain (p = 0.011), increased the rate of successful catheter placement at first
      attempt (p = 0.004), decreased the catheterisation procedure time (p = 0.001) and
      decreased nurse-perceived difficulty during catheter placement (p = 0.001).
      CONCLUSIONS: Local application of heat before the catheterisation procedure is
      suggested for patients receiving chemotherapy, particularly in cases where
      visibility of the veins is poor and intravenous catheter insertion is difficult.
      RELEVANCE TO CLINICAL PRACTICE: Local application of heat results in
      vasodilation, and thus intravenous catheter insertion becomes easier. Our
      findings have important implications for nurses who care for chemotherapy
      patients. The inclusion of local heat application before catheterisation as a
      preparation step is suitable to be implemented by nurses in other hospitals and
      clinics where chemotherapy is provided.

PMID- 27028836
TI  - Structural stabilization of a metal-organic framework for gas sorption
      investigation.
AB  - By inserting a ligand into a reported metal-organic framework (), the reformed
      aggregation of triangle grids () shows enhanced stability. In addition, owing to
      its structural characteristic, the also reveals a certain CO2 storage ability and
      CO2/CH4 adsorption selectivity as expected. 

PMID- 27028837
TI  - New Treatments for Women's Sexual and Genital Health.

PMID- 27028838
TI  - Agger-bullar classification (ABC) of the frontal sinus drainage pathway:
      validation in a preclinical setting.
AB  - BACKGROUND: The anatomy of structures surrounding the frontal sinus drainage
      pathway (FSDP) is extremely complex and challenging for endoscopic sinus
      surgeons. The anatomical nomenclature of this area reflects this complexity and
      lack of agreement regarding anatomical variants of this region is present in the
      literature. This work presents a new classification system of the air spaces
      surrounding the FSDP, called the agger-bullar classification (ABC), and compares
      it with the most widely used anatomical classification of the frontoethmoidal
      region, the modified Bent and Kuhn classification (MBKC). METHODS: Fourteen human
      heads underwent cone beam computed tomography (CT) scan and subsequently
      endoscopic dissection. Anatomical data were collected by 2 radiologists in
      consensus, an expert surgeon, and a novice surgeon. The radiologists filled the
      anatomical report after examining the CT scan, and the expert surgeon had both CT
      scan and endoscopic dissection available. A record of the dissection was obtained
      to allow the novice surgeon to compile the report. Interrater agreement regarding
      each variable of the classification systems was estimated through Cohen's kappa
      value. Cohen's kappa values of variables referring to the same anatomical subunit
      were matched to compare ABC with MBKC. RESULTS: For both air spaces in front and
      behind the FSDP, interrater agreement values of the variables of the ABC were
      significantly higher than the corresponding variables of the MBKC. CONCLUSION:
      This preclinical study demonstrates the potential of the ABC system. Although the
      ABC may improve preoperative anatomical assessment of the frontoethmoidal area,
      validation in a clinical setting is required.

PMID- 27028839
TI  - Sex differences in the management of acute coronary syndromes in Italy: data from
      the MANTRA registry.
AB  - AIMS: Several studies have shown sex differences in acute coronary syndromes
      (ACS), but their understanding is far from complete. Thus, the study aims to
      evaluate sex differences in management and outcomes of unselected patients with
      ACS. METHODS AND RESULTS: From 22 April 2009 to 29 December 2010, 6394
      consecutive patients with ACS (44.7% ST-elevation myocardial infarction) were
      prospectively enrolled and followed for 6 months. Women (N = 1894, 29.6%) were
      older, had more comorbidities, and worse clinical presentation than men. Fewer
      women underwent reperfusion [68.0% women vs. 84.1% men, P < 0.0001, adjusted odds
      ratio (OR): 0.53, 95% confidence interval (CI): 0.43-0.66] in ST-elevation
      myocardial infarction, and coronary angiography during hospitalization (72.2%
      women vs. 81.1% men, P < 0.0001, adjusted OR: 0.70, 95% CI: 0.57-0.85) in no-ST
      elevation ACS. Women had worse outcomes than men during hospitalization, and at 6
      month follow-up. At multivariable analysis, female sex was significantly
      associated with a higher risk of in-hospital Thrombolysis in Myocardial
      Infarction major bleedings (OR: 1.80, 95% CI: 1.09-2.96, P = 0.02), but not of 6
      month death. CONCLUSION: Women with ACS in clinical practice present a clustering
      of high-risk features that may contribute to their worse outcomes as compared
      with men, although female sex is not an independent predictor of death at 6-month
      follow-up.

PMID- 27028840
TI  - Evaluation of the appropriateness of the preclinical phase (stage A and stage B)
      of heart failure Management in Outpatient clinics in Italy rationale and design
      of the 'VASTISSIMO' study.
AB  - Early detection of heart failure, when still preclinical, is fundamental.
      Therefore, it is important to assess whether preclinical heart failure management
      by cardiologists is adequate. The VASTISSIMO study ('EValuation of the
      AppropriateneSs of The preclInical phase (Stage A and Stage B) of heart failure
      Management in Outpatient clinics in Italy') is a prospective nationwide study
      aimed to evaluate the appropriateness of diagnosis and management of preclinical
      heart failure (stages A and B) by cardiologists working in outpatient clinics in
      Italy. Secondary goals are to verify if an online educational course for
      cardiologists can improve management of preclinical heart failure, and evaluate
      how well cardiologists are aware of patients' adherence to medications. The study
      involves 80 outpatient cardiology clinics distributed throughout Italy,
      affiliated either to the Hospital Cardiologists Association or to the Regional
      Association of Outpatient Cardiologists, and is designed with two phases of
      consecutive outpatient enrolment each lasting 1 month. In phase 1, physicians'
      awareness of the risk of heart failure and their decision-making process are
      recorded. Subsequently, half of the cardiologists are randomized to undergo an
      online educational course aimed to improve preclinical heart failure management
      through implementation of guideline recommendations. At the end of the course,
      all cardiologists are evaluated (phase 2) to see whether changes in clinical
      management have occurred in those who underwent the educational program versus
      those who did not. Patients' adherence to prescribed medications will be assessed
      through the Morisky Self-report Questionnaire. This study should provide valuable
      information about cardiologists' awareness of preclinical heart failure and the
      appropriateness of clinical practice in outpatient cardiology clinics in Italy. 

PMID- 27028841
TI  - Index of microcirculatory resistance to evaluate the efficacy of self-expanding
      stent and thrombectomy in acute myocardial infarction.

PMID- 27028842
TI  - Alcohol-Preferring P Rats Exhibit Elevated Motor Impulsivity Concomitant with
      Operant Responding and Self-Administration of Alcohol.
AB  - BACKGROUND: Increased levels of impulsivity are associated with increased illicit
      drug use and alcoholism. Previous research in our laboratory has shown that
      increased levels of delay discounting (a decision-making form of impulsivity) are
      related to appetitive processes governing alcohol self-administration as opposed
      to purely consummatory processes. Specifically, the high-seeking/high-drinking
      alcohol-preferring P rats showed increased delay discounting compared to
      nonselected Long Evans rats (LE) whereas the high-drinking/moderate-seeking HAD2
      rats did not. The P rats also displayed a perseverative pattern of behavior such
      that during operant alcohol self-administration they exhibited greater resistance
      to extinction. METHODS: One explanation for the previous findings is that P rats
      have a deficit in response inhibition. This study followed up on this possibility
      by utilizing a countermanding paradigm (stop signal reaction time [SSRT] task)
      followed by operant self-administration of alcohol across increasing fixed ratio
      requirements (FR; 1, 2, 5, 10, and 15 responses). In separate animals, 24-hour
      access 2-bottle choice (10% EtOH vs. water) drinking was assessed. RESULTS: In
      the SSRT task, P rats exhibited an increased SSRT compared to both LE and HAD2
      rats indicating a decrease in behavioral inhibition in the P rats. Also, P rats
      showed increased operant self-administration across all FRs and the greatest
      increase in responding with increasing FR requirements. Conversely, the HAD2 and
      LE had shorter SSRTs and lower levels of operant alcohol self-administration.
      However, for 2-bottle choice drinking HAD2s and P rats consumed more EtOH and had
      a greater preference for EtOH compared to LE. CONCLUSIONS: These data extend
      previous findings showing the P rats to have increased delay discounting
      (decision-making impulsivity) and suggest that P rats also have a lack of
      behavioral inhibition (motor impulsivity). This supports the notion that P rats
      are a highly impulsive as well as "high-seeking" model of alcoholism, and that
      the HAD2s' elevated levels of alcohol consumption are not mediated via appetitive
      processes or impulsivity.

PMID- 27028843
TI  - Cannabinoid Receptor 1 Mediates Homing of Bone Marrow-Derived Mesenchymal Stem
      Cells Triggered by Chronic Liver Injury.
AB  - Cannabinoid receptors (CBs) have been implicated in the pathogenesis of various
      liver diseases, including liver fibrosis. Our previous studies have demonstrated
      that after liver injury, mouse bone marrow-derived mesenchymal stem cells (BMSCs)
      can migrate to the injured liver and differentiate to myofibroblasts,
      contributing to hepatic fibrogenesis. However, the role of CBs in the homing of
      BMSCs in liver injury is yet unclear. In this study, we found that both CB1 and
      CB2 were expressed in BMSCs. Migration assays were performed by transwell
      chambers. CB1 agonist ACEA promoted the migration of BMSCs, but CB2 agonist
      JWH133 had no effect. Pharmacological or genetic ablation of CB1 reduced ACEA
      induced migration, whereas CB2 did not. Moreover, activation of CB1 increased
      active GTP-bound Rac1, RhoA, and Cdc42 protein levels. The elevated GTP-bound
      Rac1 and RhoA protein levels were decreased by CB1 antagonist AM281 treatment,
      but not Cdc42. In addition, ACEA-induced migration was suppressed by NSC23766
      (Rac1 inhibitor) or C3 transferase (RhoA inhibitor), whereas MLS-573151 (Cdc42
      inhibitor) had no effect. Consistent with these data, Rac1 or RhoA knock-down
      significantly blocked CB1-mediated migration. Meanwhile, CB1-mediated migration
      was associated with cytoskeletal remodeling. In vivo, administration of CB1
      antagonist AM281 markedly inhibited the recruitment of BMSCs to the injured liver
      using fluorescence-activated cell sorting. Furthermore, blockade of CB1
      significantly attenuated liver fibrosis. In conclusion, our results suggest that
      CB1 plays a crucial role in liver fibrosis through mediating the homing of BMSCs
      to damaged liver, which may provide new insight into the pathogenesis and
      treatment of liver fibrosis. J. Cell. Physiol. 232: 110-121, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27028844
TI  - Successful endoscopic papillectomy in a patient with situs inversus.

PMID- 27028845
TI  - Defending victimized peers: Opposing the bully, supporting the victim, or both?
AB  - To reduce bullying, more knowledge on children defending their victimized peers
      is critical. In previous work, predominantly cross-sectional in nature, defending
      has typically been operationalized as one single, broad construct. However, there
      are good reasons to assume that attacking the bully (bully oriented defending)
      and comforting the victim (victim-oriented defending) are relatively independent
      constructs, with potentially different correlates. This longitudinal study in the
      Netherlands (N = 394; Mage  = 10.3) combined person- and variable-centered
      techniques to examine relations between two different forms of defending and
      multiple outcome variables. In addition to the largest group scoring low on both
      types of defending, three subgroups emerged. A small group of "traditional,"
      predominantly female defenders, scored high on both forms of defending. These
      children were well liked and high in reputation-based status, as indexed by
      perceived popularity and resource control. A larger, predominantly female second
      group only scored high on victim-oriented defending. These children were also
      well liked, but low in reputation-based status. The third group only scored high
      on bully oriented defending, and predominantly contained boys. These children
      were high in reputation-based status but quite disliked, and they scored high on
      bullying. Findings strongly suggest that bully oriented defending does not in all
      cases reflect desirable interventions of empathic children. Aggr. Behav. 42:585
      597, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028846
TI  - Membrane-Mediated Regulation of Embryonic Development: Highlights.

PMID- 27028847
TI  - Second-order capillary electrophoresis diode array detector data modeled with the
      Tucker3 algorithm: A novel strategy for Argentinean white wine discrimination
      respect to grape variety.
AB  - Data obtained by capillary electrophoresis with diode array detection (CE-DAD)
      were modeled with the purpose to discriminate Argentinean white wines samples
      produced from three grape varieties (Torrontes, Chardonnay, and Sauvignon blanc).
      Thirty-eight samples of commercial white wine from four wine-producing provinces
      of Argentina (Mendoza, San Juan, Salta, and Rio Negro) were analyzed. CE-DAD
      matrices with dimensions of 421 elution times (from 1.17 to 7.39 minutes) * 71
      wavelengths (from 227 to 367 nm) were joined in a three way data array and
      decomposed by Tucker3 method under non-negativity constraint, employing 18, 18
      and six factors in the modes 1, 2 and 3, respectively. Using the scores of Tucker
      model, it was possible to discriminate samples of Argentinean white wine by
      linear discriminant analysis and Kernel linear discriminant analysis. Core
      element analysis of the Tucker3 model allows identifying the loading profiles in
      spectral mode related to Argentinean white wine samples.

PMID- 27028848
TI  - Solvothermally Mediated Self-Assembly of Ultralong Peptide Nanobelts Capable of
      Optical Waveguiding.
AB  - The formation of ultralong peptide crystalline nanobelts using a solvothermal
      approach from a di-phenylalanine gel within 10 min, where the self-assembly
      process is accelerated by several orders of magnitude compared with the month
      long glutaraldehyde induction method previously reported, has been demonstrated.
      The solvothermal treatment can facilitate the phase separation of di
      phenylalanine gels while speeding up the kinetics of the intramolecular
      cyclization reaction and concomitant crystallization. Moreover, the modulation
      effect of formaldehyde as an additive is revealed, and that a small amount of
      formaldehyde leads to thicker crystalline platelets capable of curved optical
      waveguiding that can potentially be applied in advanced bio-optical and
      optoelectronic devices, a rare feat with peptide-based crystals.

PMID- 27028849
TI  - Pulmonary vasculature in COPD: The silent component.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by airflow
      obstruction that results from an inflammatory process affecting the airways and
      lung parenchyma. Despite major abnormalities taking place in bronchial and
      alveolar structures, changes in pulmonary vessels also represent an important
      component of the disease. Alterations in vessel structure are highly prevalent
      and abnormalities in their function impair gas exchange and may result in
      pulmonary hypertension (PH), an important complication of the disease associated
      with reduced survival and worse clinical course. The prevalence of PH is high in
      COPD, particularly in advanced stages, although it remains of mild to moderate
      severity in the majority of cases. Endothelial dysfunction, with imbalance
      between vasodilator/vasoconstrictive mediators, is a key determinant of changes
      taking place in pulmonary vasculature in COPD. Cigarette smoke products may
      perturb endothelial cells and play a critical role in initiating vascular
      changes. The concurrence of inflammation, hypoxia and emphysema further
      contributes to vascular damage and to the development of PH. The use of drugs
      that target endothelium-dependent signalling pathways, currently employed in
      pulmonary arterial hypertension, is discouraged in COPD due to the lack of
      efficacy observed in randomized clinical trials and because there is compelling
      evidence indicating that these drugs may worsen pulmonary gas exchange. The
      subgroup of patients with severe PH should be ideally managed in centres with
      expertise in both PH and chronic lung diseases because alterations of pulmonary
      vasculature might resemble those observed in pulmonary arterial hypertension.
      Because this condition entails poor prognosis, it warrants specialist treatment.

PMID- 27028850
TI  - Head and neck cancer in South Asia: Macroeconomic consequences and the role of
      the head and neck surgeon.
AB  - BACKGROUND: Head and neck cancer constitutes a substantial portion of the burden
      of disease in South Asia, and there is an undersupply of surgical capacity in
      this region. The purpose of this study was to estimate the economic welfare
      losses due to head and neck cancer in India, Pakistan, and Bangladesh in 2010.
      METHODS: We used publicly available estimates of head and neck cancer morbidity
      and mortality along with a concept termed the value of a statistical life to
      estimate economic welfare losses in the aforementioned countries in 2010.
      RESULTS: Economic losses because of head and neck cancer in India, Pakistan, and
      Bangladesh totaled $16.9 billion (2010 US dollars [USD]), equivalent to 0.26% of
      the region's economic output. Bangladesh, the poorest country, experienced the
      greatest proportional losses. CONCLUSION: The economic consequences of head and
      neck cancer in South Asia are significant, and building surgical capacity is
      essential to begin to address this burden. (c) 2016 Wiley Periodicals, Inc. Head
      Neck 38:1242-1247, 2016.

PMID- 27028851
TI  - Comparative genomic analysis of primary tumors and metastases in breast cancer.
AB  - Personalized medicine uses genomic information for selecting therapy in patients
      with metastatic cancer. An issue is the optimal tissue source (primary tumor or
      metastasis) for testing. We compared the DNA copy number and mutational profiles
      of primary breast cancers and paired metastases from 23 patients using whole
      genome array-comparative genomic hybridization and next-generation sequencing of
      365 "cancer-associated" genes. Primary tumors and metastases harbored copy number
      alterations (CNAs) and mutations common in breast cancer and showed concordant
      profiles. The global concordance regarding CNAs was shown by clustering and
      correlation matrix, which showed that each metastasis correlated more strongly
      with its paired tumor than with other samples. Genes with recurrent
      amplifications in breast cancer showed 100% (ERBB2, FGFR1), 96% (CCND1), and 88%
      (MYC) concordance for the amplified/non-amplified status. Among all samples, 499
      mutations were identified, including 39 recurrent (AKT1, ERBB2, PIK3CA, TP53) and
      460 non-recurrent variants. The tumors/metastases concordance of variants was
      75%, higher for recurrent (92%) than for non-recurrent (73%) variants. Further
      mutational discordance came from very different variant allele frequencies for
      some variants. We showed that the chosen targeted therapy in two clinical trials
      of personalized medicine would be concordant in all but one patient (96%) when
      based on the molecular profiling of tumor and paired metastasis. Our results
      suggest that the genotyping of primary tumor may be acceptable to guide systemic
      treatment if the metastatic sample is not obtainable. However, given the rare but
      potentially relevant divergences for some actionable driver genes, the profiling
      of metastatic sample is recommended. 

PMID- 27028852
TI  - A window of opportunity study of potential tumor and soluble biomarkers of
      response to preoperative erlotinib in early stage non-small cell lung cancer.
AB  - BACKGROUND: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some
      with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC
      to assess response and correlation with potential biomarkers. RESULTS: Twenty
      five patients were enrolled; 22 received erlotinib treatment and were evaluable
      (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although
      31% had squamous carcinoma. PET response was observed in 2 patients (9%), both
      with squamous carcinoma. Most (20/22) had stable disease (RECIST), with frequent
      minor radiographic regression and histologic findings of fibrosis/necrosis
      including in squamous histology. Only two had EGFR mutations identified, one with
      minor radiographic response and the other stable disease after 4 weeks of EGFR
      TKI. High pre-treatment serum levels of TGF-alpha correlated with primary
      resistance to erlotinib (p = 0.02), whereas high post-treatment soluble EGFR
      levels correlated with response (p = 0.03). EGFR, PTEN, cMET and AXL expression
      did not correlate with tumor response. METHODS: Clinical stage IA-IIB NSCLC
      patients received erlotinib 150 mg daily for 4 weeks followed by resection. Tumor
      response was assessed using CT, PET and pathological response. Tumor genotype was
      established using Sequenom Mass ARRAY; EGFR, PTEN, cMET and AXL expression was
      assessed by immunohistochemistry, circulating markers of EGFR activation (TGF
      alpha, amphiregulin, epiregulin, EGFR ECD) by ELISA and EGFR, MET copy number by
      FISH. CONCLUSIONS: Erlotinib appears to demonstrate activity in EGFR wild-type
      tumors including squamous carcinoma. Further research is needed to characterize
      those wild-type patients that may benefit from EGFR TKI and predictive biomarkers
      including TGF-alpha, EGFR copy and others.

PMID- 27028853
TI  - Comparative profiles of BRAF inhibitors: the paradox index as a predictor of
      clinical toxicity.
AB  - BRAF inhibitor (BRAFi) therapy is associated with the induction of neoplasia,
      most commonly cutaneous squamous cell carcinoma (cuSCC). This toxicity is
      explained in part by "paradoxical ERK activation," or the hyperactivation of ERK
      signaling by BRAFi in BRAF wild-type cells. However, the rate of cuSCC induction
      varies widely among BRAFi. To explore this mechanistically, we profiled
      paradoxical ERK activation by vemurafenib, dabrafenib, encorafenib (LGX818), and
      PLX8394, demonstrating that vemurafenib induces ERK activation the greatest,
      while dabrafenib and encorafenib have higher "paradox indices", defined as the
      pERK activation EC80 divided by the IC80 against A375, corresponding to wider
      therapeutic windows for achieving tumor inhibition without paradoxical ERK
      activation. Our results identify differences in the paradox indices of these
      compounds as a potential mechanism for the differences in cuSCC induction rates
      and highlight the utility of using ERK activity as a biomarker for maximizing the
      clinical utility of BRAFi. 

PMID- 27028854
TI  - DNA promoter hypermethylation in nipple fluid: a potential tool for early breast
      cancer detection.
AB  - INTRODUCTION: Nipple fluid aspiration provides direct non-invasive sampling of
      fluid from the mammary ductal system, where the majority of breast cancers
      originate. DNA promoter hypermethylation ("methylation") occurs early and at high
      frequency in breast carcinogenesis, bearing the potential as a biomarker for
      cancer detection at its earliest stages. We assessed methylation in nipple fluid
      from breasts of healthy women, of women with sporadic breast cancer and of their
      contralateral breasts. Our goal was to investigate whether nipple fluid can be
      used as a reliable methylation biomarker source. MATERIALS AND METHODS:
      Methylation levels of 13 genes were analysed by quantitative multiplex
      methylation specific PCR (QM-MSP) in nipple fluid samples from breasts of healthy
      women, and from the affected and contralateral breasts of breast cancer patients.
      RESULTS: Methylation analysis of the low-volume nipple fluid samples was
      feasible. Despite the generally low methylation levels, cancerous and healthy
      breasts nipple fluid could be discriminated with an area under the receiver
      operating characteristic curve (AUC) of 0.64 (p<0.01) based on a multivariate
      model including AKR1B1, ALX1, RASSF1A and TM6SF1. Within-patient differences
      between cancerous and contralateral nipple fluid samples were less prominent.
      CONCLUSIONS: Cancerous nipple fluid contains increased levels of methylation of
      tumor suppressor genes that potentially could serve as a biomarker for early
      breast cancer detection.

PMID- 27028855
TI  - Prognostic value and clinicopathologic characteristics of L1 cell adhesion
      molecule (L1CAM) in a large series of vulvar squamous cell carcinomas.
AB  - BACKGROUND: Vulvar cancer treatment is mostly curative, but also has high
      morbidity rates. In a search for markers that can identify patients at risk of
      metastases, we investigated the prognostic value of L1-cell adhesion molecule
      (L1CAM) in large series of vulvar squamous cell carcinomas (VSCCs). L1CAM
      promotes cell motility and is an emerging prognostic factor for metastasis in
      many cancer subtypes. RESULTS: L1CAM expression was observed at the invasive
      front or in spray-patterned parts of 17% of the tumours. L1CAM-positive tumours
      expressed vimentin more often, but L1CAM expression was not associated with TP53
      or CTNNB1 mutations. Five-year survival was worse for patients with L1CAM
      expression (overall survival 46.1% vs 63.6%, P=.014, disease specific survival
      63.8% vs 80.0%, P=.018). Multivariate analysis indicates L1CAM expression as an
      independent prognostic marker (HR 2.9, 95% CI 1.10-7.68). An in vitro spheroid
      invasion assay showed decreased invasion of L1CAM-expressing VSCC spindle cells
      after treatment with L1CAM-neutralising antibodies. METHODS: Paraffin-embedded
      tumour tissue from two cohorts (N=103 and 245) of primary VSCCs were stained for
      L1CAM, vimentin and E-cadherin. Patients of the first cohort were tested for
      human papilloma virus infection and sequenced for TP53 and CTNNB1 (beta-catenin)
      mutations. The expression of L1CAM was correlated to clinical characteristics and
      patient survival. CONCLUSION: This is the first study to show high L1CAM
      expression at the infiltrating margin of VSCC's. L1CAM-expressing VSCCs had a
      significantly worse prognosis compared to L1CAM-negative tumours. The highest
      expression was observed in spindle-shaped cells, where it might be correlated to
      their invasive capacity.

PMID- 27028856
TI  - Sumoylation of TCF21 downregulates the transcriptional activity of estrogen
      receptor-alpha.
AB  - Aberrant estrogen receptor-alpha (ERalpha) signaling is recognized as a major
      contributor to the development of breast cancer. However, the molecular mechanism
      underlying the regulation of ERalpha in breast cancer is still inconclusive. In
      this study, we showed that the transcription factor 21 (TCF21) interacted with
      ERalpha, and repressed its transcriptional activity in a HDACs-dependent manner.
      We also showed that TCF21 could be sumoylated by the small ubiquitin-like
      modifier SUMO1, and this modification could be reversed by SENP1. Sumoylation of
      TCF21 occurred at lysine residue 24 (K24). Substitution of K24 with arginine
      resulted in complete abolishment of sumoylation. Sumoylation stabilized TCF21,
      but did not affect its subcellular localization. Sumoylation of TCF21 also
      enhanced its interaction with HDAC1/2 without affecting its interaction with
      ERalpha. Moreover, sumoylation of TCF21 promoted its repression of ERalpha
      transcriptional activity, and increased the recruitment of HDAC1/2 to the pS2
      promoter. Consistent with these observations, sumoylation of TCF21 could inhibit
      the growth of ERalpha-positive breast cancer cells and decreased the proportion
      of S-phase cells in the cell cycle. These findings suggested that TCF21 might act
      as a negative regulator of ERalpha, and its sumoylation inhibited the
      transcriptional activity of ERalpha through promoting the recruitment of HDAC1/2.

PMID- 27028857
TI  - Chronic inflammation-associated genomic instability paves the way for human
      esophageal carcinogenesis.
AB  - Chronic inflammation is associated with increased risk of cancer development,
      whereas the link between chronic inflammation and esophageal carcinogenesis is
      still obscure heretofore. This study aimed to investigate the relationship
      between chronic inflammation and DNA damage, as well as the possible role of DNA
      damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from
      109 individuals from Chaoshan littoral, a high-risk region for esophageal
      squamous cell carcinoma (ESCC), were examined to evaluate the association between
      chronic inflammation and histological severity, while additional 204 esophageal
      non-tumor samples from patients with ESCC were collected. Immunohistochemistry
      was performed to detect the oxidative DNA damage and DNA double-strand breaks
      (DSBs). Significantly positive correlation was observed between degree of chronic
      inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01).
      Immunohistochemical analysis showed that oxidative DNA damage level was
      positively correlated with the degree of chronic inflammation (rs = 0.21, P <
      0.05). Moreover, the level of oxidative DNA damage positively correlated with
      histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was
      progressively increased with inflammation degree (P < 0.01) and the progression
      of precancerous lesions (P < 0.001). Collectively, these findings provide
      evidence linking chronic inflammation-associated genomic instability with
      esophageal carcinogenesis and suggest possibilities for early detection and
      intervention of esophageal carcinogenesis. 

PMID- 27028858
TI  - Tumor suppressor Spred2 interaction with LC3 promotes autophagosome maturation
      and induces autophagy-dependent cell death.
AB  - The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in
      a variety of cancers. However, the underlying mechanism remains to be elucidated.
      Here we show that Spred2 induces caspase-independent but autophagy-dependent cell
      death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate
      that ectopic Spred2 increased both the conversion of microtubule-associated
      protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1
      degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor
      cells inhibited upregulation of autophagosome maturation induced by the autophagy
      inducer Rapamycin, which could be reversed by the rescue Spred2. These data
      suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co
      localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in
      its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain
      impaired Spred2-mediated autophagosome maturation and tumor cell death,
      indicating that functional LIR is required for Spred2 to trigger tumor cell
      death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through
      its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa
      cells indicates that p62 may be involved in Spred2-mediated autophagosome
      maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine,
      reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy
      related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results,
      suggesting that autophagy is required for Spred2-induced tumor cell death.
      Collectively, these data indicate that Spred2 induces tumor cell death in an
      autophagy-dependent manner. 

PMID- 27028859
TI  - LIM domain only 2 over-expression in prostate stromal cells facilitates prostate
      cancer progression through paracrine of Interleukin-11.
AB  - Mechanisms of stromal-epithelial crosstalk are essential for Prostate cancer
      (PCa) tumorigenesis and progression. Peripheral zone of the prostate gland
      possesses a stronger inclination for PCa than transition zone. We previously
      found a variety of genes that differently expressed among different prostate
      stromal cells, including LIM domain only 2 (LMO2) which highly expressed in
      peripheral zone derived stromal cells (PZSCs) and PCa associated fibroblasts
      (CAFs) compared to transition zone derived stromal cells (TZSCs). Studies on its
      role in tumors have highlighted LMO2 as an oncogene. Herein, we aim to study the
      potential mechanisms of stromal LMO2 in promoting PCa progression. The in vitro
      cells co-culture and in vivo cells recombination revealed that LMO2 over
      expressed prostate stromal cells could promote the proliferation and invasiveness
      of either prostate epithelial or cancer cells. Further protein array screening
      confirmed that stromal LMO2 stimulated the secretion of Interleukin-11 (IL-11),
      which could promote proliferation and invasiveness of PCa cells via IL-11
      receptor alpha (IL11Ralpha) - STAT3 signaling. Moreover, stromal LMO2 over
      expression could suppress miR-204-5p which was proven to be a negative regulator
      of IL-11 expression. Taken together, results of our study demonstrate that
      prostate stromal LMO2 is capable of stimulating IL-11 secretion and by which
      activates IL11Ralpha - STAT3 signaling in PCa cells and then facilitates PCa
      progression. These results may make stromal LMO2 responsible for zonal
      characteristic of PCa and as a target for PCa microenvironment-targeted therapy. 

PMID- 27028860
TI  - Grapefruit-derived nanovectors deliver miR-18a for treatment of liver metastasis
      of colon cancer by induction of M1 macrophages.
AB  - Liver metastasis accounts for many of the cancer deaths in patients. Effective
      treatment for metastatic liver tumors is not available. Here, we provide evidence
      for the role of miR-18a in the induction of liver M1 (F4/80+interferon gamma
      (IFNgamma)+IL-12+) macrophages. We found that miR-18a encapsulated in grapefruit
      derived nanovector (GNV) mediated inhibition of liver metastasis that is
      dependent upon the induction of M1 (F4/80+IFNgamma+IL-12+) macrophages; depletion
      of macrophages eliminated its anti-metastasis effect. Furthermore, the miR-18a
      mediated induction of macrophage IFNgamma by targeting IRF2 is required for
      subsequent induction of IL-12. IL-12 then activates natural killer (NK) and
      natural killer T (NKT) cells for inhibition of liver metastasis of colon cancer.
      This conclusion is supported by the fact that knockout of IFNgamma eliminates miR
      18a mediated induction of IL-12, miR-18a treatment has an anti-metastatic effects
      in T cell deficient mice but there is no anti-metastatic effect on NK and NKT
      deficient mice. Co-delivery of miR-18a and siRNA IL-12 to macrophages did not
      result in activation of co-cultured NK and NKT cells. Taken together our results
      indicate that miR-18a can act as an inhibitor for liver metastasis through
      induction of M1 macrophages. 

PMID- 27028861
TI  - E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.
AB  - Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions
      induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA
      sites is the initial step in their repair, and requires multiprotein complexes
      that contain XPC and hHR23 proteins, or their orthologues. A variety of
      transcription factors are also involved in NER, including E2F1. In epidermal
      keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to
      recruit various NER factors to sites of DNA damage. However, the relationship
      between E2F1 and hHR23 proteins vis-a-vis NER has remained unexplored. We now
      show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes
      E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A
      subcellular localization, recruiting it to sites of DNA photodamage. As a result,
      E2F1 and hHR23A enhance DNA repair following exposure to UV radiation,
      contributing to genomic stability in the epidermis. 

PMID- 27028862
TI  - Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis
      lung carcinoma in mice fed a high-fat diet.
AB  - Adipose-produced pro-inflammatory cytokines contribute to obesity and cancer.
      This 2x2 experiment was designed to investigate effects of monocyte chemotactic
      protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma
      (LLC) in MCP-1 deficient and wild-type mice fed a modified AIN93G diet containing
      16% and 45% of energy from corn oil, respectively. The high-fat diet
      significantly increased the number and size (cross-sectional area and volume) of
      lung metastases compared to the AIN93G control diet. Deficiency in MCP-1 reduced
      lung metastases by 37% in high-fat diet-fed mice; it reduced metastatic cross
      sectional area by 46% and volume by 69% compared to wild-type mice. Adipose and
      plasma concentrations of MCP-1 were significantly higher in high-fat diet-fed
      wild-type mice than in their AIN93G-fed counterparts; they were not detectable in
      MCP-1 deficient mice regardless of diet. Plasma concentrations of plasminogen
      activator inhibitor-1, tumor necrosis factor-alpha, vascular endothelial growth
      factor and tissue inhibitor of metalloproteinase-1 were significantly higher in
      MCP-1 deficient mice compared to wild-type mice. We conclude that adipose
      produced MCP-1 contributes to high-fat diet-enhanced metastasis. While MCP-1
      deficiency reduces metastasis, the elevation of pro-inflammatory cytokines and
      angiogenic factors in the absence of MCP-1 may support the metastatic development
      and growth of LLC in MCP-1 deficient mice. 

PMID- 27028863
TI  - Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in
      bone marrow.
AB  - GAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in
      regulating tumor progression in a number of settings. Previously we have
      demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy
      induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that
      GAS6 secreted from osteoblasts in the bone marrow environment plays a critical
      role in establishing prostate tumor cell dormancy. Here we investigated the role
      that endogenous GAS6 and Mer receptor signaling plays in establishing prostate
      cancer stem cells in the bone marrow microenvironment.We first observed that high
      levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the
      bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in
      PCa tumors grown in a s.c. SETTING: Interestingly, elevated levels of endogenous
      GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared
      to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and
      in DTCs isolated from the bone marrow 24 hours after intracardiac injection.
      Moreover, we found that endogenous GAS6 expression is associated with Mer
      receptor expression in growth arrested (G1) PCa cells, which correlates with the
      increase of the CSC populations. Importantly, we found that overexpression of
      GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction
      of the CSC phenotype in vitro and in vivo.Together these data suggest that
      endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa
      CSCs in the bone marrow microenvironment, which may have important implications
      for targeting metastatic disease.

PMID- 27028864
TI  - Androgen receptor regulates SRC expression through microRNA-203.
AB  - The SRC kinase has pivotal roles in multiple developmental processes and in tumor
      progression. An inverse relationship has been observed between androgen receptor
      (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the
      modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we
      showed that patients with high SRC levels displayed correspondingly low canonical
      AR gene signatures. Our results demonstrated that activated AR induced miR-203
      and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3' UTR
      of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we
      found that progressive PCa cell migration and growth were associated with a
      decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR,
      miR-203, and SRC were also confirmed in clinical datasets and specimens. We
      suggest that the induction of SRC results in increased PCa metastasis that is
      linked to the dysregulation of the AR signaling pathway through the inactivation
      of miR-203. 

PMID- 27028865
TI  - Altered neutrophil immunophenotypes in childhood B-cell precursor acute
      lymphoblastic leukemia.
AB  - An increasing number of evidences suggest a genetic predisposition in acute
      lymphoblastic leukemia (ALL) that might favor the occurrence of the driver
      genetic alterations. Such genetic background might also translate into phenotypic
      alterations of residual hematopoietic cells. Whether such phenotypic alterations
      are present in bone marrow (BM) cells from childhood B-cell precursor (BCP)-ALL
      remains to be investigated. Here we analyzed the immunophenotypic profile of BM
      and peripheral blood (PB) maturing/matured neutrophils from 118 children with BCP
      ALL and their relationship with the features of the disease. Our results showed
      altered neutrophil phenotypes in most (77%) BCP-ALL cases. The most frequently
      altered marker was CD10 (53%), followed by CD33 (34%), CD13 (15%), CD15/CD65
      (10%) and CD123 (7%). Of note, patients with altered neutrophil phenotypes had
      younger age (p = 0.03) and lower percentages of BM maturing neutrophils (p =
      0.004) together with greater BM lymphocyte (p = 0.04), and mature B-cell (p =
      0.03) counts. No significant association was found between an altered neutrophil
      phenotype and other disease features. These findings point out the potential
      existence of an altered residual hematopoiesis in most childhood BCP-ALL cases. 

PMID- 27028866
TI  - Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor
      heterogeneity and increases survival.
AB  - Melanoma risk is increased in patients with mutations of melanocortin 1 receptor
      (MC1R) yet the basis for the increased risk remains unknown. Here we report in
      vivo evidence supporting a critical role for MC1R in regulating melanoma tumor
      growth and determining overall survival time. Inhibition of MC1R by its
      physiologically relevant competitive inhibitor, agouti signaling protein (ASIP),
      reduced melanin synthesis and morphological heterogeneity in murine B16-F10
      melanoma cells. In the lungs of syngeneic C57BL/6 mice, mCherry-marked, ASIP
      secreting lung tumors inhibited MC1R on neighboring tumors lacking ASIP in a dose
      dependent manner as evidenced by a proportional loss of pigment in tumors from
      mice injected with 1:1, 3:1 and 4:1 mixtures of parental B16-F10 to ASIP
      expressing tumor cells. ASIP-expressing B16-F10 cells formed poorly pigmented
      tumors in vivo that correlated with a 20% longer median survival than those
      bearing parental B16-F10 tumors (p=0.0005). Mice injected with 1:1 mixtures also
      showed survival benefit (p=0.0054), whereas injection of a 4:1 mixture showed no
      significant difference in survival. The longer survival time of mice bearing ASIP
      expressing tumors correlated with a significantly slower growth rate than
      parental B16-F10 tumors as judged by quantification of numbers of tumors and
      total tumor load (p=0.0325), as well as a more homogeneous size and morphology of
      ASIP-expressing lung tumors. We conclude that MC1R plays an important role in
      regulating melanoma growth and morphology. Persistent inhibition of MC1R provided
      a significant survival advantage resulting in part from slower tumor growth,
      establishing MC1R as a compelling new molecular target for metastatic melanoma. 

PMID- 27028867
TI  - Functional interplay between cylindromatosis and histone deacetylase 6 in ciliary
      homeostasis revealed by phenotypic analysis of double knockout mice.
AB  - Cilia are present in most vertebrate tissues with a wide variety of functions,
      and abnormalities of cilia are linked to numerous human disorders. However, the
      molecular events underlying ciliary homeostasis are poorly understood. In this
      study, we generated double knockout (DKO) mice for the deubiquitinase
      cylindromatosis (CYLD) and histone deacetylase 6 (HDAC6), two critical ciliary
      regulators. The Cyld/Hdac6 DKO mice were phenotypically normal and showed no
      obvious variances in weight or behavior compared with their wild-type
      littermates. Strikingly, Cyld loss-induced ciliary defects in the testis,
      trachea, and kidney were abrogated in the Cyld/Hdac6 DKO mice. In addition, the
      diminished alpha-tubulin acetylation and impaired sonic hedgehog signaling caused
      by loss of Cyld were largely restored by simultaneous deletion of Hdac6. We
      further found by immunofluorescence microscopy a colocalization of CYLD and HDAC6
      at the centrosome/basal body and, interestingly, loss of Cyld promoted the
      localization of HDAC6 at the centrosome/basal body. These findings provide
      physiological insight into the ciliary role of the CYLD/HDAC6 axis and suggest a
      functional interplay between these two proteins in ciliary homeostasis. 

PMID- 27028868
TI  - RSK-mediated down-regulation of PDCD4 is required for proliferation, survival,
      and migration in a model of triple-negative breast cancer.
AB  - The p90 ribosomal S6 kinase (RSK) is a family of MAPK-activated serine/threonine
      kinases (RSK1-4) whose expression and/or activity are deregulated in several
      cancers, including breast cancer. Up-regulation of RSKs promotes cellular
      processes that drive tumorigenesis in Triple Negative Breast Cancer (TNBC) cells.
      Although RSKs regulate protein synthesis in certain cell types, the role of RSK
      mediated translational control in oncogenic progression has yet to be evaluated.
      We demonstrate that proliferation and migration of TNBC MDA-MB-231 cells, unlike
      ER/PR-positive MCF7 cells, rely on RSK activity. We show that RSKs regulate the
      activities of the translation initiation factor eIF4B and the translational
      repressor PDCD4 in TNBC cells with up-regulated MAPK pathway, but not in breast
      cancer cells with hyperactivated PI3K/Akt/mTORC1 pathway. These results identify
      PDCD4 as a novel RSK substrate. We demonstrate that RSK-mediated phosphorylation
      of PDCD4 at S76 promotes PDCD4 degradation. Low PDCD4 levels reduce PDCD4
      inhibitory effect on the translation initiation factor eIF4A, which increases
      translation of "eIF4A sensitive" mRNAs encoding factors involved in cell cycle
      progression, survival, and migration. Consequently, low levels of PDCD4 favor
      proliferation and migration of MDA-MB-231 cells. These results support the
      therapeutic use of RSK inhibitors for treatment of TNBC with deregulated MAPK/RSK
      pathway. 

PMID- 27028869
TI  - IFN-alpha potentiates the direct and immune-mediated antitumor effects of
      epigenetic drugs on both metastatic and stem cells of colorectal cancer.
AB  - Epigenetic alterations, including dysregulated DNA methylation and histone
      modifications, govern the progression of colorectal cancer (CRC). Cancer cells
      exploit epigenetic regulation to control cellular pathways, including apoptotic
      and metastatic signals. Since aberrations in epigenome can be pharmacologically
      reversed by DNA methyltransferase and histone deacetylase inhibitors, epigenetics
      in combination with standard agents are currently envisaged as a new therapeutic
      frontier in cancer, expected to overcome drug resistance associated with current
      treatments. In this study, we challenged this idea and demonstrated that the
      combination of azacitidine and romidepsin with IFN-alpha owns a high therapeutic
      potential, targeting the most aggressive cellular components of CRC, such as
      metastatic cells and cancer stem cells (CSCs), via tight control of key survival
      and death pathways. Moreover, the antitumor efficacy of this novel
      pharmacological approach is associated with induction of signals of immunogenic
      cell death. Of note, a previously undisclosed key role of IFN-alpha in inducing
      both antiproliferative and pro-apoptotic effects on CSCs of CRC was also found.
      Overall, these findings open a new frontier on the suitability of IFN-alpha in
      association with epigenetics as a novel and promising therapeutic approach for
      CRC management. 

PMID- 27028871
TI  - Projections of Water Stress Based on an Ensemble of Socioeconomic Growth and
      Climate Change Scenarios: A Case Study in Asia.
AB  - The sustainability of future water resources is of paramount importance and is
      affected by many factors, including population, wealth and climate. Inherent in
      current methods to estimate these factors in the future is the uncertainty of
      their prediction. In this study, we integrate a large ensemble of scenarios-
      internally consistent across economics, emissions, climate, and population--to
      develop a risk portfolio of water stress over a large portion of Asia that
      includes China, India, and Mainland Southeast Asia in a future with unconstrained
      emissions. We isolate the effects of socioeconomic growth from the effects of
      climate change in order to identify the primary drivers of stress on water
      resources. We find that water needs related to socioeconomic changes, which are
      currently small, are likely to increase considerably in the future, often
      overshadowing the effect of climate change on levels of water stress. As a
      result, there is a high risk of severe water stress in densely populated
      watersheds by 2050, compared to recent history. There is strong evidence to
      suggest that, in the absence of autonomous adaptation or societal response, a
      much larger portion of the region's population will live in water-stressed
      regions in the near future. Tools and studies such as these can effectively
      investigate large-scale system sensitivities and can be useful in engaging and
      informing decision makers.

PMID- 27028870
TI  - An optimized single chain TCR scaffold relying on the assembly with the native
      CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.
AB  - Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically
      engineered with tumor-specific heterodimeric alpha/beta T-cell receptors
      (TCRalpha/beta). However, potential mispairing of introduced TCRalpha/beta-chains
      with endogenous beta/alpha-ones may evoke unpredictable autoimmune reactivities.
      A novel single chain (sc)TCR format relies on the fusion of the Valpha-Linker
      Vbeta-fragment to the TCR Cbeta-domain and coexpression of the TCR Calpha-domain
      capable of recruiting the natural CD3-complex for full and hence, native T-cell
      signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor
      antigen-specific scTCR is still prone to mispairing with TCRalpha. In a human
      Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of
      a scTCR could be reconstituted by any cointroduced TCRalpha-chain indicating
      mispairing to take place on a molecular basis. In contrast, transduction into
      human TCRalpha/beta-positive T-cells revealed that mispairing is largely reduced.
      Competition experiments in Jurkat-76 confirmed the preference of dcTCR to
      selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR
      modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell
      activation in CMV-infected tumor patients. Residual mispairing was prevented by
      strenghtening the Valpha-Li-Vbeta-fragment through the design of a novel
      disulfide bond between a Valpha- and a linker-resident residue close to Vbeta.
      Multimer-stainings, and cytotoxicity-, IFNgamma-secretion-, and CFSE
      proliferation-assays, the latter towards dendritic cells endogenously processing
      RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRalpha
      formation without impairing avidity of scTCR/Calpha in T-cells. Moreover, a
      fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired
      enhanced cytotoxicity. Thus, optimized scTCR/Calpha inhibits residual TCR
      mispairing to accomplish safe adoptive immunotherapy for bulk endogenous
      TCRalpha/beta-positive T-cells. 

PMID- 27028872
TI  - Inhibition of the Myotoxicity Induced by Bothrops jararacussu Venom and Isolated
      Phospholipases A2 by Specific Camelid Single-Domain Antibody Fragments.
AB  - Antivenoms, produced using animal hyperimmune plasma, remains the standard
      therapy for snakebites. Although effective against systemic damages, conventional
      antivenoms have limited efficacy against local tissue damage. Additionally, the
      hypersensitivity reactions, often elicited by antivenoms, the high costs for
      animal maintenance, the difficulty of producing homogeneous lots, and the
      instability of biological products instigate the search for innovative products
      for antivenom therapy. In this study, camelid antibody fragments (VHH) with
      specificity to Bothropstoxin I and II (BthTX-I and BthTX-II), two myotoxic
      phospholipases from Bothrops jararacussu venom, were selected from an immune VHH
      phage display library. After biopanning, 28 and 6 clones recognized BthTX-I and
      BthTX-II by ELISA, respectively. Complementarity determining regions (CDRs) and
      immunoglobulin frameworks (FRs) of 13 VHH-deduced amino acid sequences were
      identified, as well as the camelid hallmark amino acid substitutions in FR2.
      Three VHH clones (KF498607, KF498608, and KC329718) were capable of recognizing
      BthTX-I by Western blot and showed affinity constants in the nanomolar range
      against both toxins. VHHs inhibited the BthTX-II phospholipase A2 activity, and
      when tested for cross-reactivity, presented specificity to the Bothrops genus in
      ELISA. Furthermore, two clones (KC329718 and KF498607) neutralized the myotoxic
      effects induced by B. jararacussu venom, BthTX-I, BthTX-II, and by a myotoxin
      from Bothrops brazili venom (MTX-I) in mice. Molecular docking revealed that VHH
      CDRs are expected to bind the C-terminal of both toxins, essential for myotoxic
      activity, and to epitopes in the BthTX-II enzymatic cleft. Identified VHHs could
      be a biotechnological tool to improve the treatment for snake envenomation, an
      important and neglected world public health problem. 

PMID- 27028874
TI  - Dream Doctor Intervention Instead of Sedation: Performing Radionuclide Scanning
      Without Sedation in Young Children: A Study in 142 Patients.
AB  - BACKGROUND: Dream Doctors (DDs; professional medical clowns) are expanding their
      activities in pediatric wards. DDs were introduced as an alternative to sedation
      among children undergoing kidney imaging after urinary infection. The imaging
      requires that the patient lie completely still under the camera during the scan;
      otherwise the image cannot be interpreted. It is extremely difficult to get these
      children to cooperate, and pediatricians have to provide sedation to get good
      results. Giving sedation requires medical observation, and it can take hours
      until the child can be safely released from the hospital. METHODS: A DD
      intervention was introduced in an attempt to avoid sedation in these young
      children. The DD tried to gain the child's cooperation during the procedure. Each
      study was subsequently scored by a radionuclide physician to assess study quality
      and interpretation. RESULTS: A total of 142 patients were studied over a 14-month
      period. The mean age was 2 +/- 1.6 years. During the study, in the presence of
      the DD, only five (3.2%) patients required pharmacologic sedation compared with
      100% before the study. CONCLUSIONS: The introduction of DDs proved to be a good
      alternative to sedation in cases where the procedure does not involve pain and
      only requires the child's cooperation.

PMID- 27028875
TI  - Factors affecting performance and productivity of nurses: professional attitude,
      organisational justice, organisational culture and mobbing.
AB  - AIM: To identify relationships among variables affecting nurses' performance and
      productivity, namely professional attitudes, organisational culture,
      organisational justice and exposure to mobbing. BACKGROUND: The determination of
      the factors affecting performance and productivity is important for providing
      efficient nursing services. These factors have been investigated in the
      literature independently, but the relationship among them has not been clearly
      identified. METHODS: This cross-sectional questionnaire study included 772 nurses
      working in a University Hospital accredited by Joint Commission International.
      RESULTS: The professional attitude score of the nurses was high (4.35 +/- 0.63).
      However, their organisational justice (2.22 +/- 1.26) and organisational culture
      (2.47 +/- 0.71) scores were low. Nurses were subjected to mobbing at a high level
      (0.82 +/- 0.78). As the organisational justice increased, the organisational
      culture increased and the mobbing decreased. As the organisation culture
      decreased, the mobbing increased. CONCLUSIONS: There was a positive correlation
      between organisation culture and organisational justice of the nurses and a
      negative correlation with mobbing. IMPLICATIONS FOR NURSING MANAGEMENT: The
      results of the study are essential for improving nurses' performance and
      productivity.

PMID- 27028873
TI  - Integration of Social, Cultural, and Biomedical Strategies into an Existing
      Couple-Based Behavioral HIV/STI Prevention Intervention: Voices of Latino Male
      Couples.
AB  - INTRODUCTION: Successful HIV prevention and treatment requires evidence-based
      approaches that combine biomedical strategies with behavioral interventions that
      are socially and culturally appropriate for the population or community being
      prioritized. Although there has been a push for a combination approach, how best
      to integrate different strategies into existing behavioral HIV prevention
      interventions remains unclear. The need to develop effective combination
      approaches is of particular importance for men who have sex with men (MSM), who
      face a disproportionately high risk of HIV acquisition. MATERIALS AND METHODS: We
      collaborated with Latino male couples and providers to adapt Connect 'n Unite, an
      evidence-based intervention for Black male couples, for Latino male couples. We
      conducted a series of three focus groups, each with two cohorts of couples, and
      one focus group with providers. A purposive stratified sample of 20 couples (N =
      40, divided into two cohorts) and 10 providers provided insights into how to
      adapt and integrate social, cultural, and biomedical approaches in a couples
      based HIV/AIDS behavioral intervention. RESULTS: The majority (N = 37) of the
      couple participants had no prior knowledge of the following new biomedical
      strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure
      prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to
      these biomedical interventions, all participants expressed a need for information
      and empowerment through knowledge and awareness of these interventions. In
      particular, participants suggested that we provide PrEP and HIV self-testing kits
      by the middle or end of the intervention. Providers suggested a need to address
      behavioral, social and structural issues, such as language barriers; and the
      promotion of client-centered approaches to increase access to, adaptation of, and
      adherence to biomedical strategies. Corroborating what couple participants
      suggested, providers agreed that biomedical strategies should be offered after
      providing information about these tools. Regarding culturally sensitive and
      responsive approaches, participants identified stigma and discrimination
      associated with HIV and sexual identity as barriers to care, language barriers
      and documentation status as further barriers to care, the couple-based approach
      as ideal to health promotion, and the need to include family topics in the
      intervention. DISCUSSION: We successfully adapted an evidence-based behavioral
      HIV prevention intervention for Latino male couples. The adapted intervention,
      called Conectando Latinos en Pareja, integrates social, cultural, behavioral and
      biomedical strategies to address the HIV epidemic among Latino MSM. The study
      highlights the promise regarding the feasibility of implementing a combination
      approach to HIV prevention in this population.

PMID- 27028876
TI  - First case of redness and erosion at bacillus Calmette-Guerin inoculation site
      after vaccination against influenza.

PMID- 27028877
TI  - Disarming an Electrophilic Warhead: Retaining Potency in Tyrosine Kinase
      Inhibitor (TKI)-Resistant CML Lines While Circumventing Pharmacokinetic
      Liabilities.
AB  - Pharmacologic blockade of the activation of signal transducer and activator of
      transcription 3 (STAT3) in tyrosine kinase inhibitor (TKI)-resistant chronic
      myeloid leukemia (CML) cell lines characterized by kinase-independent resistance
      was shown to re-sensitize CML cells to TKI therapy, suggesting that STAT3
      inhibitors in combination with TKIs are an effective combinatorial therapeutic
      for the treatment of CML. Benzoic acid- and hydroxamic acid-based STAT3
      inhibitors SH-4-054 and SH-5-007, developed previously in our laboratory,
      demonstrated promising activity against these resistant CML cell lines. However,
      pharmacokinetic studies in murine models (CD-1 mice) revealed that both SH-4-054
      and SH-5-007 are susceptible to glutathione conjugation at the para position of
      the pentafluorophenyl group via nucleophilic aromatic substitution (SN Ar). To
      determine whether the electrophilicity of the pentafluorophenyl sulfonamide could
      be tempered, an in-depth structure-activity relationship (SAR) study of the SH-4
      054 scaffold was conducted. These studies revealed that AM-1-124, possessing a
      2,3,5,6-tetrafluorophenylsulfonamide group, retained STAT3 protein affinity (Ki
      =15 MUm), as well as selectivity over STAT1 (Ki >250 MUm). Moreover, in both
      hepatocytes and in in vivo pharmacokinetic studies (CD-1 mice), AM-1-124 was
      found to be dramatically more stable than SH-4-054 (t1/2 =1.42 h cf. 10 min,
      respectively). AM-1-124 is a promising STAT3-targeting inhibitor with
      demonstrated bioavailability, suitable for evaluation in preclinical cancer
      models. 

PMID- 27028878
TI  - Dental Care for Survivors of Adolescent and Young Adult Cancer: Special
      Considerations.
AB  - PURPOSE: Oral health is important for quality of life, but may be undermanaged
      for survivors of cancer. We examine dental care use and barriers among long-term
      survivors of adolescent and young adult (AYA) cancer in comparison to individuals
      without a history of cancer. METHODS: The 2008-2012 Medical Expenditure Panel
      Survey (MEPS) identified 1216 individuals diagnosed with cancer at AYA ages (15
      39 years), who were at least 5 years from diagnosis. A comparison group was
      matched using age, sex, and other factors. We evaluated self-reported dental
      visits in the previous 12 months, and inability and delay in receiving necessary
      dental care among survivors and the comparison group. Furthermore, individual
      factors associated with dental care use were identified using multivariable
      logistic regressions. RESULTS: Of survivors, 60.86% reported no dental visits in
      the previous year compared to 51.96% of the comparison individuals (p < 0.001).
      Survivors were more likely to report inability (10.71% vs. 6.29%, p = 0.001) and
      delay (8.12% vs. 4.45%, p = 0.001) in getting necessary dental care than the
      comparison group. Notably, survivors without dental insurance were more likely to
      report inability and delay. Female survivors were more likely to use dental care
      than males (odds ratio = 1.76, 95% confidence interval 1.15-2.71, p = 0.01).
      Hispanic survivors, those diagnosed at younger ages, and uninsured survivors were
      less likely to have at least one dental visit. CONCLUSION: Survivors of AYA
      cancer need timely surveillance to manage late effects, including dental
      complications. Yet, these survivors, particularly those who are uninsured, delay
      dental care more often than individuals from the general population. Survivor
      specific interventions are needed to reduce dental care barriers.

PMID- 27028879
TI  - Anti-N-methyl-D-aspartate receptor encephalitis with lung adenocarcinoma.

PMID- 27028880
TI  - Limited effect of ozone reductions on the 20-year photosynthesis trend at Harvard
      forest.
AB  - Ozone (O3 ) damage to leaves can reduce plant photosynthesis, which suggests that
      declines in ambient O3 concentrations ([O3 ]) in the United States may have
      helped increase gross primary production (GPP) in recent decades. Here, we assess
      the effect of long-term changes in ambient [O3 ] using 20 years of observations
      at Harvard forest. Using artificial neural networks, we found that the effect of
      the inclusion of [O3 ] as a predictor was slight, and independent of O3
      concentrations, which suggests limited high-frequency O3 inhibition of GPP at
      this site. Simulations with a terrestrial biosphere model, however, suggest an
      average long-term O3 inhibition of 10.4% for 1992-2011. A decline of [O3 ] over
      the measurement period resulted in moderate predicted GPP trends of 0.02-0.04
      MUmol C m-2  s-1  yr-1 , which is negligible relative to the total observed GPP
      trend of 0.41 MUmol C m-2  s-1  yr-1 . A similar conclusion is achieved with the
      widely used AOT40 metric. Combined, our results suggest that ozone reductions at
      Harvard forest are unlikely to have had a large impact on the photosynthesis
      trend over the past 20 years. Such limited effects are mainly related to the slow
      responses of photosynthesis to changes in [O3 ]. Furthermore, we estimate that
      40% of photosynthesis happens in the shade, where stomatal conductance and thus
      [O3 ] deposition is lower than for sunlit leaves. This portion of GPP remains
      unaffected by [O3 ], thus helping to buffer the changes of total photosynthesis
      due to varied [O3 ]. Our analyses suggest that current ozone reductions, although
      significant, cannot substantially alleviate the damages to forest ecosystems.

PMID- 27028881
TI  - Laryngeal Cancer: 12-Year Experience of a Single Center.
AB  - Laryngeal cancer is about the twentieth most common cancer in the world and more
      than 150,000 new cases are diagnosed annually. The aim of the study was to
      evaluate the history, diagnostics, treatment outcomes, and prognosis in patients
      with laryngeal cancer in Northern Slovakia. We analyzed retrospectively 227
      patients (207 males, 20 females) with laryngeal carcinoma treated in the period
      2003-2014 at the Clinic of Otorhinolaryngology and Head and Neck Surgery of the
      Jessenius Faculty of Medicine and Martin University Hospital in Martin, Slovakia.
      The majority of patients were in the sixth (38.0 %) and seventh decade of life
      (30.8 %). Two hundred and seventeen patients (95.6 %) were smokers or ex-smokers.
      Sixty-six percent of patients were diagnosed with glottic or transglottic
      carcinoma, related probably to the anatomical structure of the larynx and
      exposure to inhalation pollutants. It is alarming that the majority of patients
      with malignant laryngeal disease were admitted to the hospital in advanced
      stages. In 151 (66.5 %) of patients, the extent of infiltration was T3 or T4, and
      156 (68 %) patients were in disease stage III and IV. The incidence and mortality
      of laryngeal cancer suggest the need to intensify the prevention and to search
      for an early clinical stage of laryngeal cancer using a targeted screening.

PMID- 27028882
TI  - [In Process Citation].

PMID- 27028883
TI  - Progesterone for preterm labour.

PMID- 27028885
TI  - Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3
      dependent Necroptosis.
AB  - RIP3-dependent necroptosis has recently garnered significant interest because of
      the unique signaling mechanisms and pathologic functions involved in this
      process. Accordingly, a number of chemical screens have identified several
      effective small-molecule inhibitors that specifically block necroptosis. Here, we
      report the discovery that kongensin A (KA), a natural product isolated from
      Croton kongensis, is a potent inhibitor of necroptosis and an inducer of
      apoptosis. Using a new bioorthogonal ligation method (TQ ligation), we reveal
      that the direct cellular target of KA is heat shock protein 90 (HSP90). Further
      studies demonstrate that KA covalently binds to a previously uncharacterized
      cysteine 420 in the middle domain of HSP90 and dissociates HSP90 from its
      cochaperone CDC37, which leads to inhibition of RIP3-dependent necroptosis and
      promotion of apoptosis in multiple cancer cell lines. Collectively, our findings
      demonstrate that KA is an effective HSP90 inhibitor that has potential anti
      necroptosis and anti-inflammation applications. 

PMID- 27028886
TI  - Trehalose Polyphleates Are Produced by a Glycolipid Biosynthetic Pathway
      Conserved across Phylogenetically Distant Mycobacteria.
AB  - Mycobacteria synthesize a variety of structurally related glycolipids with major
      biological functions. Common themes have emerged for the biosynthesis of these
      glycolipids, including several families of proteins. Genes encoding these
      proteins are usually clustered on bacterial chromosomal islets dedicated to the
      synthesis of one glycolipid family. Here, we investigated the function of a
      cluster of five genes widely distributed across non-tuberculous mycobacteria.
      Using defined mutant analysis and in-depth structural characterization of
      glycolipids from wild-type or mutant strains of Mycobacterium smegmatis and
      Mycobacterium abscessus, we established that they are involved in the formation
      of trehalose polyphleates (TPP), a family of compounds originally described in
      Mycobacterium phlei. Comparative genomics and lipid analysis of strains
      distributed along the mycobacterial phylogenetic tree revealed that TPP is
      synthesized by a large number of non-tuberculous mycobacteria. This work unravels
      a novel glycolipid biosynthetic pathway in mycobacteria and extends the spectrum
      of bacteria that produce TPP. 

PMID- 27028884
TI  - Structural Characterization and Bioactivity Analysis of the Two-Component
      Lantibiotic Flv System from a Ruminant Bacterium.
AB  - The discovery of new ribosomally synthesized and post-translationally modified
      peptide natural products (RiPPs) has greatly benefitted from the influx of
      genomic information. The lanthipeptides are a subset of this class of compounds.
      Adopting the genome-mining approach revealed a novel lanthipeptide gene cluster
      encoded in the genome of Ruminococcus flavefaciens FD-1, an anaerobic bacterium
      that is an important member of the rumen microbiota of livestock. The post
      translationally modified peptides were produced via heterologous expression in
      Escherichia coli. Subsequent structural characterization and assessment of their
      bioactivity revealed features reminiscent of and distinct from previously
      reported lanthipeptides. The lanthipeptides of R. flavefaciens FD-1 represent a
      unique example within two-component lanthipeptides, consisting of a highly
      conserved alpha-peptide and a diverse set of eight beta-peptides.

PMID- 27028887
TI  - Accurate Prediction of Ligand Affinities for a Proton-Dependent Oligopeptide
      Transporter.
AB  - Membrane transporters are critical modulators of drug pharmacokinetics, efficacy,
      and safety. One example is the proton-dependent oligopeptide transporter PepT1,
      also known as SLC15A1, which is responsible for the uptake of the ?-lactam
      antibiotics and various peptide-based prodrugs. In this study, we modeled the
      binding of various peptides to a bacterial homolog, PepT(St), and evaluated a
      range of computational methods for predicting the free energy of binding. Our
      results show that a hybrid approach (endpoint methods to classify peptides into
      good and poor binders and a theoretically exact method for refinement) is able to
      accurately predict affinities, which we validated using proteoliposome transport
      assays. Applying the method to a homology model of PepT1 suggests that the
      approach requires a high-quality structure to be accurate. Our study provides a
      blueprint for extending these computational methodologies to other
      pharmaceutically important transporter families.

PMID- 27028889
TI  - Components of the type six secretion system are substrates of Francisella
      tularensis Schu S4 DsbA-like FipB protein.
AB  - FipB, an essential virulence factor in the highly virulent Schu S4 strain of F.
      tularensis subsp. tularensis, shares sequence similarity with Disulfide Bond
      formation (Dsb) proteins, which can have oxidoreductase, isomerase, or chaperone
      activity. To further explore FipB's role in virulence potential substrates were
      identified by co-purification and 2D gel electrophoresis, followed by protein
      sequencing using mass spectrometry. A total of 119 potential substrates were
      identified. Proteins with predicted enzymatic activity were prevalent, and there
      were 19 proteins that had been previously identified as impacting virulence.
      Among the potential substrates were IglC, IglB, and PdpB, three components of the
      Francisella Type Six Secretion System (T6SS), which is also essential for
      virulence. T6SS are widespread in Gram-negative pathogens, but have not been
      reported to be dependent on Dsb-like proteins for assembly or function. The
      presented results suggest that FipB affects IglB and IglC substrates differently.
      In a fipB mutant there were differences in free sulfhydryl accessibility of IglC,
      but not IglB, when compared to wild-type bacteria. However, for both proteins
      FipB appears to act as a chaperone that facilitates proper folding and
      conformation. Understanding the role FipB plays the assembly and structure in
      this T6SS may reveal critical aspects of assembly that are common and novel among
      this widely distributed class of secretion systems.

PMID- 27028890
TI  - Effect of gingival inflammation on the inflammatory response in patients with
      idiopathic uveitis.
AB  - OBJECTIVES: This study aimed to investigate the levels of 11 oral species in
      plaque samples and cytokine levels in biofluid samples of patients with
      idiopathic uveitis (IU) and systemically healthy individuals (H) with or without
      gingival inflammation. MATERIAL & METHODS: Twenty-one patients with IU (n = 21),
      and 22 systemically healthy individuals (n = 22) were enrolled in the study.
      Clinical periodontal measurements were recorded. Cytokine levels in the biofluid
      samples were determined by ELISA. Bacterial gene copy numbers were determined by
      qPCR on plaque microbial DNA preparations. RESULTS: According to two-step cluster
      analysis, anova and t-test: GCF, serum and salivary TNF-alpha, IL-17A, IL-17A/E;
      GCF and serum IL-6; salivary IL-17F, and salivary and serum IL-17A/F levels were
      higher in the IU group than the H group (p < 0.05). However, serum IL-10 and IL
      17E levels were higher in the H group than the IU group (p < 0.05). A.
      actinomycetemcomitans, F. nucleatum, S. oralis, A. naeslundii, and V. dispar
      counts were higher in IU group compared to H group (p < 0.05). CONCLUSION:
      Altered local and systemic cytokine profiles are associated with differences in
      the microbial plaque composition in IU. Anti-inflammatory cytokines; IL-10, IL
      17E are reduced in patients with IU and Th-1 and Th-17 driven inflammatory
      responses in biofluids are altered.

PMID- 27028891
TI  - Antibiotic resistance due to an unusual ColE1-type replicon plasmid in Aeromonas
      salmonicida.
AB  - Aeromonas salmonicida subsp. salmonicida is a fish pathogen known to have a rich
      plasmidome. In the present study, we discovered an isolate of this bacterium
      bearing an additional unidentified small plasmid. After having sequenced the DNA
      of that isolate by next-generation sequencing, it appeared that the new small
      plasmid is a ColE1-type replicon plasmid, named here pAsa7. This plasmid bears a
      functional chloramphenicol-acetyltransferase-encoding gene (cat-pAsa7) previously
      unknown in A. salmonicida and responsible for resistance to chloramphenicol. A
      comparison of pAsa7 with pAsa2, the only known ColE1-type replicon plasmid
      usually found in A. salmonicida subsp. salmonicida, revealed that even if both
      plasmids share a high structural similarity, it is still unclear if pAsa7 is a
      derivative of pAsa2 since they showed several mutations at the nucleotide level.
      Transcriptomic analysis revealed that the cat-pAsa4 gene, another chloramphenicol
      acetyltransferase-encoding gene, found on the large plasmid pAsa4, was
      significantly more transcribed than cat-pAsa7. This was correlated with a higher
      chloramphenicol resistance for isolates bearing pAsa4 compared with the one
      having pAsa7. Finally, a phylogenetic analysis showed that both CAT-pAsa4 and CAT
      pAsa7 proteins were in different clusters. The clustering was supported by the
      identity of residues involved in the catalytic site. In addition, to give a
      better understanding of the large drug-resistance panel of A. salmonicida, this
      study reinforces the hypothesis that A. salmonicida subsp. salmonicida is a
      considerable reservoir for mobile genetic elements such as plasmids.

PMID- 27028893
TI  - Effects of Antibiotics on Gut Microbiota.
AB  - The gut microbiota influences essential human functions including digestion,
      energy metabolism, and inflammation by modulating multiple endocrine, neural, and
      immune pathways of the host. Its composition and complexity varies markedly
      across individuals and across different sites of the gut, but provides a certain
      level of resilience against external perturbation. Short-term antibiotic
      treatment is able to shift the gut microbiota to long-term alternative dysbiotic
      states, which may promote the development and aggravation of disease. Common
      features of post-antibiotic dysbiosis include a loss of taxonomic and functional
      diversity combined with reduced colonization resistance against invading
      pathogens, which harbors the danger of antimicrobial resistance. This review
      summarizes the antibiotic-related changes of the gut microbiota and potential
      consequences in health and disease. 

PMID- 27028892
TI  - Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by
      Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway.
AB  - Galectin-9 is a widely expressed protein that is involved in immune regulation
      and tumorpathogenesis and serves as a marker of a poor prognosis in various types
      of cancers. However, the clinical impact and the precise mechanism by which this
      protein contributes to colon tumor progression are unclear. In the present study,
      we detected the expression of galectin-9 and CD56 cells using
      immunohistochemistry. Spearman's rank correlation was used to clarify the
      association between galectin-9 expression and natural killer (NK) cell
      infiltration. The influence of galectin-9 on NK-92 cell migration was evaluated
      in vitro using transwell chemotaxis assays. The role of rh-galectin-9 in F-actin
      polarization in NK-92 cells was investigated using laser scanning confocal
      microscopy. We showed that galectin-9 was expressed in 101 (78.91%) colon tumor
      tissues and that was expressed at lower levels in these tissues than in para
      tumor tissues. Low levels of galectin-9 expression were positively correlated
      with a poor histological grade and lymph node metastasis (P<0.05). A Kaplan-Meier
      method and Cox proportional hazards regression analysis showed that overall
      survival was longer in patients with high galectin-9 expression in an 8-year
      follow-up (P<0.05). Spearman's rank correlation indicated that there was a linear
      correlation between galectin-9 expression and CD56+ NK cell infiltration (R(2) =
      0.658; P<0.0001). Galectin-9 stimulated migration in human NK-92 cells by
      affecting F-actin polarization through the Rho/ROCK1 signaling pathway. These
      results suggest that galectin-9 expression potentially represents a novel
      mechanism for tumors to escape immune surveillance in colon tumors.

PMID- 27028894
TI  - Age-related maintenance of eccentric strength: a study of temperature dependence.
AB  - With adult aging, eccentric strength is maintained better than isometric strength
      leading to a higher ratio of eccentric/isometric force production (ECC/ISO) in
      older than younger adults. The purpose was to investigate the ECC/ISO during
      electrical activation of the adductor pollicis during lengthening (20-320 degrees
      s(-1)) contractions in 24 young (n = 12, ~24 years) and old (n = 12, ~72 years)
      males across muscle temperatures (cold ~19  degrees C; normal ~30  degrees C;
      warm ~35  degrees C). For isometric force, the old were 20-30 % weaker in the
      normal and cold conditions (P < 0.05) with no difference for the warm condition
      compared to young (P > 0.05). Half-relaxation time (HRT) did not differ across
      age for the normal and warm temperatures (P > 0.05), but it slowed significantly
      for old in the cold condition compared with young (~15 %; P < 0.05), as well,
      there was a 20 and 40 % increase in muscle stiffness for the young and old,
      respectively. ECC/ISO was 50-60 % greater for the cold condition than the normal
      and warm conditions. There was no age difference in ECC/ISO across ages for the
      normal and warm conditions (P > 0.05), but for the cold, the old exhibited a 20
      35 % higher ECC/ISO than did the young for velocities above 60 degrees  s(-1) (P
      < 0.05). A contributing factor to the elevated ECC/ISO is an increased proportion
      of weakly compared to strongly bound crossbridges. These findings highlight the
      relationship (r = 0.70) between intrinsic muscle contractile speed (HRT) and
      eccentric strength in old age. 

PMID- 27028895
TI  - A Genuine Jahn-Teller System with Compressed Geometry and Quantum Effects
      Originating from Zero-Point Motion.
AB  - First-principle calculations together with analysis of the experimental data
      found for 3d(9) and 3d(7) ions in cubic oxides proved that the center found in
      irradiated CaO:Ni(2+) corresponds to Ni(+) under a static Jahn-Teller effect
      displaying a compressed equilibrium geometry. It was also shown that the
      anomalous positive g? shift (g? -g0 =0.065) measured at T=20 K obeys the
      superposition of the |3 z(2) -r(2) ? and |x(2) -y(2) ? states driven by quantum
      effects associated with the zero-point motion, a mechanism first put forward by
      O'Brien for static Jahn-Teller systems and later extended by Ham to the dynamic
      Jahn-Teller case. To our knowledge, this is the first genuine Jahn-Teller system
      (i.e. in which exact degeneracy exists at the high-symmetry configuration)
      exhibiting a compressed equilibrium geometry for which large quantum effects
      allow experimental observation of the effect predicted by O'Brien. Analysis of
      the calculated energy barriers for different Jahn-Teller systems allowed us to
      explain the origin of the compressed geometry observed for CaO:Ni(+) . 

PMID- 27028896
TI  - Longterm results of liver transplantation from donation after circulatory death.
AB  - Donation after circulatory death (DCD) liver transplantation (LT) may imply a
      risk for decreased graft survival, caused by posttransplantation complications
      such as primary nonfunction or ischemic-type biliary lesions. However, similar
      survival rates for DCD and donation after brain death (DBD) LT have been
      reported. The objective of this study is to determine the longterm outcome of DCD
      LT in the Eurotransplant region corrected for the Eurotransplant donor risk index
      (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003
      to December 31, 2007) in adult recipients were included. Graft failure was
      defined as either the date of recipient death or retransplantation whichever
      occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years.
      In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses
      showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%,
      respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02),
      and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038).
      Although there was an overall significant difference, the survival curves almost
      reach each other after 10 years, which is most likely caused by other risk
      factors being less in DCD livers. Patient survival was not significantly
      different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio
      of 1.7 (P < 0.001) for DCD (corrected for ET-DRI and recipient factors). First
      warm ischemia time (WIT), which is the time from the end of circulation until
      aortic cold perfusion, over 25 minutes was associated with a lower graft survival
      in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT
      has an increased risk for diminished graft survival compared to DBD. There was no
      significant difference in patient survival. DCD allografts with a first WIT > 25
      minutes have an increased risk for a decrease in graft survival. Liver
      Transplantation 22 1107-1114 2016 AASLD.

PMID- 27028898
TI  - Tuning the Electrochemical Reactivity of Boron- and Nitrogen-Substituted
      Graphene.
AB  - The structural modification of nanomaterials at the atomic level has the
      potential to generate tailor-made components with enhanced performance for a
      variety of tasks. The chemical versatility of graphene has been constantly
      employed to fabricate multi-functional doped 2D materials with applications
      encompassing energy storage and electrocatalysis. Despite the many reports on
      boron- and nitrogen-doped graphenes, the possible synergy that arises from
      combining these electronically complementary elements has yet to be fully
      understood and explored. The techniques used for the fabrication of these
      nanomaterials are reviewed, along with the most recent reports on the benefits of
      B, N singly doping and co-doping in the electrocatalysis for oxygen reduction
      reactions and for energy storage in supercapacitors and lithium secondary
      batteries. The investigation of bulk co-doped materials has intrinsic limitations
      in fully understanding the real role of heteroatoms in the above applications.
      Ultimately, the design and creation of substituted monolayers with controlled
      compositions might hold the key for carbon-based energy-related applications. 

PMID- 27028897
TI  - Strong Selection Significantly Increases Epistatic Interactions in the Long-Term
      Evolution of a Protein.
AB  - Epistatic interactions between residues determine a protein's adaptability and
      shape its evolutionary trajectory. When a protein experiences a changed
      environment, it is under strong selection to find a peak in the new fitness
      landscape. It has been shown that strong selection increases epistatic
      interactions as well as the ruggedness of the fitness landscape, but little is
      known about how the epistatic interactions change under selection in the long
      term evolution of a protein. Here we analyze the evolution of epistasis in the
      protease of the human immunodeficiency virus type 1 (HIV-1) using protease
      sequences collected for almost a decade from both treated and untreated patients,
      to understand how epistasis changes and how those changes impact the long-term
      evolvability of a protein. We use an information-theoretic proxy for epistasis
      that quantifies the co-variation between sites, and show that positive
      information is a necessary (but not sufficient) condition that detects epistasis
      in most cases. We analyze the "fossils" of the evolutionary trajectories of the
      protein contained in the sequence data, and show that epistasis continues to
      enrich under strong selection, but not for proteins whose environment is
      unchanged. The increase in epistasis compensates for the information loss due to
      sequence variability brought about by treatment, and facilitates adaptation in
      the increasingly rugged fitness landscape of treatment. While epistasis is
      thought to enhance evolvability via valley-crossing early-on in adaptation, it
      can hinder adaptation later when the landscape has turned rugged. However, we
      find no evidence that the HIV-1 protease has reached its potential for evolution
      after 9 years of adapting to a drug environment that itself is constantly
      changing. We suggest that the mechanism of encoding new information into pairwise
      interactions is central to protein evolution not just in HIV-1 protease, but for
      any protein adapting to a changing environment. 

PMID- 27028899
TI  - Exploratory field trial of motorcycle autonomous emergency braking (MAEB):
      Considerations on the acceptability of unexpected automatic decelerations.
AB  - OBJECTIVE: Autonomous emergency braking (AEB) acts to slow down a vehicle when an
      unavoidable impending collision is detected. In addition to documented benefits
      when applied to passenger cars, AEB has also shown potential when applied to
      motorcycles (MAEB). However, the feasibility of MAEB as practically applied to
      motorcycles in the real world is not well understood. METHODS: In this study we
      performed a field trial involving 16 riders on a test motorcycle subjected to
      automatic decelerations, thus simulating MAEB activation. The tests were
      conducted along a rectilinear path at nominal speed of 40 km/h and with mean
      deceleration of 0.15 g (15% of full braking) deployed at random times. Riders
      were also exposed to one final undeclared brake activation with the aim of
      providing genuinely unexpected automatic braking events. RESULTS: Participants
      were consistently able to manage automatic decelerations of the vehicle with
      minor to moderate effort. Results of undeclared activations were consistent with
      those of standard runs. CONCLUSIONS: This study demonstrated the feasibility of a
      moderate automatic deceleration in a scenario of motorcycle travelling in a
      straight path, supporting the notion that the application of AEB on motorcycles
      is practicable. Furthermore, the proposed field trial can be used as a reference
      for future regulation or consumer tests in order to address safety and
      acceptability of unexpected automatic decelerations on a motorcycle.

PMID- 27028900
TI  - The use of control charts by laypeople and hospital decision-makers for guiding
      decision making.
AB  - Graphs presenting healthcare data are increasingly available to support laypeople
      and hospital staff's decision making. When making these decisions, hospital staff
      should consider the role of chance-that is, random variation. Given random
      variation, decision-makers must distinguish signals (sometimes called special
      cause data) from noise (common-cause data). Unfortunately, many graphs do not
      facilitate the statistical reasoning necessary to make such distinctions. Control
      charts are a less commonly used type of graph that support statistical thinking
      by including reference lines that separate data more likely to be signals from
      those more likely to be noise. The current work demonstrates for whom (laypeople
      and hospital staff) and when (treatment and investigative decisions) control
      charts strengthen data-driven decision making. We present two experiments that
      compare people's use of control and non-control charts to make decisions between
      hospitals (funnel charts vs. league tables) and to monitor changes across time
      (run charts with control lines vs. run charts without control lines). As
      expected, participants more accurately identified the outlying data using a
      control chart than using a non-control chart, but their ability to then apply
      that information to more complicated questions (e.g., where should I go for
      treatment?, and should I investigate?) was limited. The discussion highlights
      some common concerns about using control charts in hospital settings.

PMID- 27028901
TI  - Persistent Prefrontal Engagement Despite Improvements in Laparoscopic Technical
      Skill.

PMID- 27028902
TI  - Locomotor, discriminative stimulus, and place conditioning effects of MDAI in
      rodents.
AB  - 5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (+/-)
      3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce
      MDMA-like discriminative stimulus effects, but it is not known whether MDAI has
      psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor
      stimulant effects in mice and subsequently for discriminative stimulus effects in
      rats trained to discriminate cocaine (10 mg/kg, intraperitoneally),
      methamphetamine (1 mg/kg, intraperitoneally), +/-MDMA (1.5 mg/kg,
      intraperitoneally), or (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5
      mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned
      place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed
      locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at
      1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg
      MDAI. Similarly, MDMA depressed locomotor activity immediately following the
      administration of 0.25 mg/kg and stimulant effects were observed 50-70 min
      following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the
      discriminative stimulus effects of MDMA (2.5 mg/kg), (-)-2,5-dimethoxy-4
      methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced
      only 73% methamphetamine-appropriate responding at a dose that suppressed
      responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine
      trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The
      effects of MDAI on locomotor activity and drug discrimination were similar to
      those produced by MDMA, having both psychostimulant-like and hallucinogen-like
      effects; thus, MDAI may have similar abuse potential as MDMA.

PMID- 27028903
TI  - Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn
      planarians.
AB  - Planarians spend less time in light versus dark environments. We hypothesized
      that planarians withdrawn from cocaine or ethanol would spend even less time in
      the light than drug-naive planarians and that a benzodiazepine would inhibit this
      response. Planarians pretreated in cocaine or ethanol were placed at the midline
      of a Petri dish containing spring water that was split evenly into dark and light
      compartments. Planarians withdrawn from cocaine (1, 10, 100 MUmol/l) or ethanol
      (0.01%) spent less time in the light compartment than water controls; however,
      this withdrawal response to cocaine (100 MUmol/l) or ethanol (0.01%) was
      abolished by clorazepate (0-100 MUmol/l). These data suggest that planarians,
      similar to rodents, show benzodiazepine-sensitive, anxiogenic-like responses
      during cocaine or alcohol withdrawal.

PMID- 27028904
TI  - A qualitative investigation into patients' perspectives on edentulousness.
AB  - OBJECTIVES: This study explored the experiences of edentulous patients for their
      perceptions of tooth loss and patient attitudes to treatment options for
      rehabilitation of the edentate state. METHODS: Purposive sampling was used to
      recruit edentate patients with varying denture-wearing experience from two dental
      hospitals in the Republic of Ireland. Sixteen edentate patients, aged 59 to 83
      years, of whom 12 were women and four men were interviewed. Interviews were
      transcribed, and thematic analysis was undertaken. RESULTS: Findings from this
      study reflect previous studies, whereby some patients indicated dissatisfaction
      with the functionality of their dentures. The majority of participants had no
      regret regarding the loss of their teeth, and despite dissatisfaction with
      dentures, they would not consider other forms of treatment. Finance was not
      considered an issue in determining whether to seek out treatment by these
      participants. These participants expressed a reluctance to get new dentures in
      case they were more problematic. CONCLUSION: This study illustrates that some
      elder edentate patients were dissatisfied with the functionality of their
      dentures and raised concerns that about the quality of dentures which may be
      provided to them by dentists. These participants identified clinical dental
      technicians as a preferred point of contact for their care. Consideration should
      be given to new oral healthcare delivery models which are accessible and
      acceptable to future elders.

PMID- 27028905
TI  - A20 plays a critical role in the immunoregulatory function of mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSCs) possess an immunoregulatory capacity and are a
      therapeutic target for many inflammation-related diseases. However, the detailed
      mechanisms of MSC-mediated immunosuppression remain unclear. In this study, we
      provide new information to partly explain the molecular mechanisms of
      immunoregulation by MSCs. Specifically, we found that A20 expression was induced
      in MSCs by inflammatory cytokines. Knockdown of A20 in MSCs resulted in increased
      proliferation and reduced adipogenesis, and partly reversed the suppressive
      effect of MSCs on T cell proliferation in vitro and inhibited tumour growth in
      vivo. Mechanistic studies indicated that knockdown of A20 in MSCs inhibited
      activation of the p38 mitogen-activated protein kinase (MAPK) pathway, which
      potently promoted the production of tumour necrosis factor (TNF)-alpha and
      inhibited the production of interleukin (IL)-10. Collectively, these data reveal
      a crucial role of A20 in regulating the immunomodulatory activities of MSCs by
      controlling the expression of TNF-alpha and IL-10 in an inflammatory environment.
      These findings provide novel insights into the pathogenesis of various
      inflammatory-associated diseases, and are a new reference for the future
      development of treatments for such afflictions.

PMID- 27028906
TI  - Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically
      Discovered Fragment Hits: A Case Study.
AB  - Fragment-based lead discovery (FBLD) has become a pillar in drug development.
      Typical applications of this method comprise at least two biophysical screens as
      prefilter and a follow-up crystallographic experiment on a subset of fragments.
      Clearly, structural information is pivotal in FBLD, but a key question is whether
      such a screening cascade strategy will retrieve the majority of fragment-bound
      structures. We therefore set out to screen 361 fragments for binding to
      endothiapepsin, a representative of the challenging group of aspartic proteases,
      employing six screening techniques and crystallography in parallel.
      Crystallography resulted in the very high number of 71 structures. Yet
      alarmingly, 44% of these hits were not detected by any biophysical screening
      approach. Moreover, any screening cascade, building on the results from two or
      more screening methods, would have failed to predict at least 73% of these hits.
      We thus conclude that, at least in the present case, the frequently applied
      biophysical prescreening filters deteriorate the number of possible X-ray hits
      while only the immediate use of crystallography enables exhaustive retrieval of a
      maximum of fragment structures, which represent a rich source guiding hit-to-lead
      to-drug evolution.

PMID- 27028908
TI  - Immersion Day--Transforming Governance and Policy by Putting on Scrubs.

PMID- 27028909
TI  - The Science of Choosing Wisely--Overcoming the Therapeutic Illusion.

PMID- 27028907
TI  - The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and
      autoantibody phenotypes, and outcomes.
AB  - The aim of this review was to summarize recent advances in the understanding of
      the clinical and autoantibody phenotypes, their associated outcomes and the
      pathogenesis of the juvenile idiopathic inflammatory myopathies (JIIMs). The
      major clinical and autoantibody phenotypes in children have many features similar
      to those in adults, and each has distinct demographic and clinical features and
      associated outcomes. The most common myositis autoantibodies in JIIM patients are
      anti-p155/140, anti-MJ and anti-MDA5. Higher mortality has been associated with
      overlap myositis as well as with the presence of anti-synthetase and anti-MDA5
      autoantibodies; a chronic illness course and lipodystrophy have been associated
      with anti-p155/140 autoantibodies; and calcinosis has been associated with anti
      MJ autoantibodies. Histologic abnormalities of JIIMs detectable on muscle biopsy
      have also been correlated with myositis-specific autoantibodies; for example,
      patients with anti-MDA5 show low levels of inflammatory infiltrate and muscle
      damage on biopsy. The first genome-wide association study of adult and juvenile
      dermatomyositis revealed three novel genetic associations, BLK, PLCL1 and CCL21
      and confirmed that the human leucocyte antigen region is the primary risk region
      for juvenile dermatomyositis. Here, we review the well-established pathogenic
      processes in JIIMs, including the type 1 interferon and endoplasmic reticulum
      stress pathways. Several novel JIIM-associated inflammatory mediators, such as
      the innate immune system proteins, myeloid-related peptide 8/14, galectin 9 and
      eotaxin, have emerged as promising biomarkers of disease. Advances in our
      understanding of the phenotypes and pathophysiology of the JIIMs are leading to
      better tools to help clinicians stratify and treat these heterogeneous disorders.

PMID- 27028910
TI  - Federal Research Regulations for the 21st Century.

PMID- 27028911
TI  - Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease.
AB  - BACKGROUND: The treatment of persistent symptoms attributed to Lyme disease
      remains controversial. We assessed whether longer-term antibiotic treatment of
      persistent symptoms attributed to Lyme disease leads to better outcomes than does
      shorter-term treatment. METHODS: In a randomized, double-blind, placebo
      controlled trial conducted in Europe, we assigned patients with persistent
      symptoms attributed to Lyme disease--either related temporally to proven Lyme
      disease or accompanied by a positive IgG or IgM immunoblot assay for Borrelia
      burgdorferi--to receive a 12-week oral course of doxycycline, clarithromycin plus
      hydroxychloroquine, or placebo. All study groups received open-label intravenous
      ceftriaxone for 2 weeks before initiating the randomized regimen. The primary
      outcome measure was health-related quality of life, as assessed by the physical
      component summary score of the RAND-36 Health Status Inventory (RAND SF-36)
      (range, 15 to 61, with higher scores indicating better quality of life), at the
      end of the treatment period at week 14, after the 2-week course of ceftriaxone
      and the 12-week course of the randomized study drug or placebo had been
      completed. RESULTS: Of the 281 patients who underwent randomization, 280 were
      included in the modified intention-to-treat analysis (86 patients in the
      doxycycline group, 96 in the clarithromycin-hydroxychloroquine group, and 98 in
      the placebo group). The SF-36 physical-component summary score did not differ
      significantly among the three study groups at the end of the treatment period,
      with mean scores of 35.0 (95% confidence interval [CI], 33.5 to 36.5) in the
      doxycycline group, 35.6 (95% CI, 34.2 to 37.1) in the clarithromycin
      hydroxychloroquine group, and 34.8 (95% CI, 33.4 to 36.2) in the placebo group
      (P=0.69; a difference of 0.2 [95% CI, -2.4 to 2.8] in the doxycycline group vs.
      the placebo group and a difference of 0.9 [95% CI, -1.6 to 3.3] in the
      clarithromycin-hydroxychloroquine group vs. the placebo group); the score also
      did not differ significantly among the groups at subsequent study visits
      (P=0.35). In all study groups, the SF-36 physical-component summary score
      increased significantly from baseline to the end of the treatment period
      (P<0.001). The rates of adverse events were similar among the study groups. Four
      serious adverse events thought to be related to drug use occurred during the 2
      week open-label ceftriaxone phase, and no serious drug-related adverse event
      occurred during the 12-week randomized phase. CONCLUSIONS: In patients with
      persistent symptoms attributed to Lyme disease, longer-term antibiotic treatment
      did not have additional beneficial effects on health-related quality of life
      beyond those with shorter-term treatment. (Funded by the Netherlands Organization
      for Health Research and Development ZonMw; PLEASE ClinicalTrials.gov number,
      NCT01207739.).

PMID- 27028912
TI  - Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.
AB  - BACKGROUND: Data suggest that estrogen-containing hormone therapy is associated
      with beneficial effects with regard to cardiovascular disease when the therapy is
      initiated temporally close to menopause but not when it is initiated later.
      However, the hypothesis that the cardiovascular effects of postmenopausal hormone
      therapy vary with the timing of therapy initiation (the hormone-timing
      hypothesis) has not been tested. METHODS: A total of 643 healthy postmenopausal
      women were stratified according to time since menopause (<6 years [early
      postmenopause] or >=10 years [late postmenopause]) and were randomly assigned to
      receive either oral 17beta-estradiol (1 mg per day, plus progesterone [45 mg]
      vaginal gel administered sequentially [i.e., once daily for 10 days of each 30
      day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal
      gel for women with a uterus). The primary outcome was the rate of change in
      carotid-artery intima-media thickness (CIMT), which was measured every 6 months.
      Secondary outcomes included an assessment of coronary atherosclerosis by cardiac
      computed tomography (CT), which was performed when participants completed the
      randomly assigned regimen. RESULTS: After a median of 5 years, the effect of
      estradiol, with or without progesterone, on CIMT progression differed between the
      early and late postmenopause strata (P=0.007 for the interaction). Among women
      who were less than 6 years past menopause at the time of randomization, the mean
      CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per
      year in the estradiol group (P=0.008). Among women who were 10 or more years past
      menopause at the time of randomization, the rates of CIMT progression in the
      placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year,
      respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis,
      and plaque did not differ significantly between the placebo group and the
      estradiol group in either postmenopause stratum. CONCLUSIONS: Oral estradiol
      therapy was associated with less progression of subclinical atherosclerosis
      (measured as CIMT) than was placebo when therapy was initiated within 6 years
      after menopause but not when it was initiated 10 or more years after menopause.
      Estradiol had no significant effect on cardiac CT measures of atherosclerosis in
      either postmenopause stratum. (Funded by the National Institute on Aging,
      National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).

PMID- 27028913
TI  - Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice
      Offenders.
AB  - BACKGROUND: Extended-release naltrexone, a sustained-release monthly injectable
      formulation of the full mu-opioid receptor antagonist, is effective for the
      prevention of relapse to opioid dependence. Data supporting its effectiveness in
      U.S. criminal justice populations are limited. METHODS: In this five-site, open
      label, randomized trial, we compared a 24-week course of extended-release
      naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and
      referrals for community treatment programs, for the prevention of opioid relapse
      among adult criminal justice offenders (i.e., persons involved in the U.S.
      criminal justice system) who had a history of opioid dependence and a preference
      for opioid-free rather than opioid maintenance treatments and who were abstinent
      from opioids at the time of randomization. The primary outcome was the time to an
      opioid-relapse event, which was defined as 10 or more days of opioid use in a 28
      day period as assessed by self-report or by testing of urine samples obtained
      every 2 weeks; a positive or missing sample was computed as 5 days of opioid use.
      Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS: A total of
      153 participants were assigned to extended-release naltrexone and 155 to usual
      treatment. During the 24-week treatment phase, participants assigned to extended
      release naltrexone had a longer median time to relapse than did those assigned to
      usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence
      interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of
      participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate
      of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI,
      1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment
      phase), rates of opioid-negative urine samples were equal (46% in each group,
      P=0.91). The rates of other prespecified secondary outcome measures--self
      reported cocaine, alcohol, and intravenous drug use, unsafe sex, and
      reincarceration--were not significantly lower with extended-release naltrexone
      than with usual treatment. Over the total 78 weeks observed, there were no
      overdose events in the extended-release naltrexone group and seven in the usual
      treatment group (P=0.02). CONCLUSIONS: In this trial involving criminal justice
      offenders, extended-release naltrexone was associated with a rate of opioid
      relapse that was lower than that with usual treatment. Opioid-use prevention
      effects waned after treatment discontinuation. (Funded by the National Institute
      on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

PMID- 27028914
TI  - Baricitinib in Patients with Refractory Rheumatoid Arthritis.
AB  - BACKGROUND: In phase 2 studies, baricitinib, an oral Janus kinase 1 and 2
      inhibitor, reduced disease activity in patients with rheumatoid arthritis who had
      not previously received treatment with biologic disease-modifying antirheumatic
      drugs (DMARDs). METHODS: In this phase 3 study involving 527 patients with an
      inadequate response to or unacceptable side effects associated with one or more
      tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly
      assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg
      daily or placebo for 24 weeks. End points, tested hierarchically at week 12 to
      control type 1 error, were the American College of Rheumatology 20% (ACR20)
      response (primary end point), the Health Assessment Questionnaire-Disability
      Index (HAQ-DI) score, the 28-joint Disease Activity Score based on C-reactive
      protein level (DAS28-CRP), and a Simplified Disease Activity Index (SDAI) score
      of 3.3 or less (on a scale of 0.1 to 86.0, with a score of 3.3 or less indicating
      remission). Comparisons with placebo were made first with the 4-mg dose of
      baricitinib and then with the 2-mg dose. RESULTS: Significantly more patients
      receiving baricitinib at the 4-mg dose than those receiving placebo had an ACR20
      response at week 12 (55% vs. 27%, P<0.001). Differences between the higher-dose
      baricitinib group and the placebo group were also significant for the HAQ-DI
      score and the DAS28-CRP but not for an SDAI score of 3.3 or less. Adverse-event
      rates through 24 weeks were higher for patients receiving the 2-mg dose of
      baricitinib and those receiving the 4-mg dose than for patients receiving placebo
      (71% and 77%, respectively, vs. 64%), including infections (44% and 40%, vs.
      31%). The rates of serious adverse events were 4%, 10%, and 7% in the three
      groups, respectively. Two nonmelanoma skin cancers and two major adverse
      cardiovascular events, including a fatal stroke, occurred in the higher-dose
      group. Baricitinib was associated with a small reduction in neutrophil levels and
      increases in serum creatinine and low-density lipoprotein cholesterol levels.
      CONCLUSIONS: In patients with rheumatoid arthritis and an inadequate response to
      biologic DMARDs, baricitinib at a daily dose of 4 mg was associated with clinical
      improvement at 12 weeks. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov
      number, NCT01721044.).

PMID- 27028915
TI  - Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies.

PMID- 27028916
TI  - IMAGES IN CLINICAL MEDICINE. Paget's Disease of Bone.

PMID- 27028917
TI  - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 10-2016. A 22-Year-Old
      Man with Sickle Cell Disease, Headache, and Difficulty Speaking.

PMID- 27028918
TI  - Time for a Different Approach to Lyme Disease and Long-Term Symptoms.

PMID- 27028919
TI  - Postmenopausal Hormone Therapy and Atherosclerosis--Time Is of the Essence.

PMID- 27028920
TI  - Genetic Targeting of the Albumin Locus to Treat Hemophilia.

PMID- 27028921
TI  - Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.

PMID- 27028922
TI  - Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.

PMID- 27028923
TI  - Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.

PMID- 27028924
TI  - Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.

PMID- 27028925
TI  - Malignant Transformation of Hymenolepis nana in a Human Host.

PMID- 27028926
TI  - Malignant Transformation of Hymenolepis nana in a Human Host.

PMID- 27028927
TI  - Thyroid Nodules.

PMID- 27028928
TI  - Thyroid Nodules.

PMID- 27028929
TI  - Thyroid Nodules.

PMID- 27028930
TI  - Nonmedical Prescription-Opioid Use and Heroin Use.

PMID- 27028931
TI  - Nonmedical Prescription-Opioid Use and Heroin Use.

PMID- 27028932
TI  - Two Cases of Vaccine-Derived Poliovirus Infection in an Oncology Ward.

PMID- 27028933
TI  - Effect of Removal of Planned Parenthood from the Texas Women's Health Program.

PMID- 27028934
TI  - IMAGES IN CLINICAL MEDICINE. Carotid-Cavernous Sinus Fistula.

PMID- 27028936
TI  - Synthesis of a Carbodicyclopropenylidene: A Carbodicarbene based Solely on
      Carbon.
AB  - The first carbodicarbene stabilized by flanking cyclopropenylidenes is reported.
      Tetraphenylcarbodicyclopropenylidene (2) is accessed by deprotonation of the
      corresponding triafulvene cyclopropenium salt, and has been spectroscopically
      characterized in [D8 ]THF solution at -60  degrees C. Main-group and transition
      metal complexes of 2 have been accessed, and have revealed the high sigma
      donating ability, and exclusive eta(1) binding of this neutral all carbon ligand.
      Variable temperature NMR spectroscopy studies reveal varying degrees of free
      rotation in the flanking cyclopropenylidene groups of 2 in its coordination
      compounds.

PMID- 27028937
TI  - Sensitivities and utility of non-invasive serological tests in the diagnosis of
      bullous pemphigoid.

PMID- 27028935
TI  - Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and
      Treatment of HIV-1 Clade C Infection.
AB  - The identification of a new generation of potent broadly neutralizing HIV-1
      antibodies (bnAbs) has generated substantial interest in their potential use for
      the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs
      targeting distinct epitopes on the viral envelope (Env) will likely be required
      to overcome the extraordinary diversity of HIV-1, a key outstanding question is
      which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We
      assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes
      of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3
      glycan region, and the gp41 membrane proximal external region (MPER), against a
      panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model
      was developed that predicted neutralization by a subset of experimentally
      evaluated bnAb combinations with high accuracy. Using this model, we performed a
      comprehensive and systematic comparison of the predicted neutralizing activity of
      over 1,600 possible double, triple, and quadruple bnAb combinations. The most
      promising bnAb combinations were identified based not only on breadth and potency
      of neutralization, but also other relevant measures, such as the extent of
      complete neutralization and instantaneous inhibitory potential (IIP). By this set
      of criteria, triple and quadruple combinations of bnAbs were identified that were
      significantly more effective than the best double combinations, and further
      improved the probability of having multiple bnAbs simultaneously active against a
      given virus, a requirement that may be critical for countering escape in vivo.
      These results provide a rationale for advancing bnAb combinations with the best
      in vitro predictors of success into clinical trials for both the prevention and
      treatment of HIV-1 infection. 

PMID- 27028938
TI  - Conservation of structural fluctuations in homologous protein kinases and its
      implications on functional sites.
AB  - Our aim is to explore the similarities in structural fluctuations of homologous
      kinases. Gaussian Network Model based Normal Mode Analysis was performed on 73
      active conformation structures in Ser/Thr/Tyr kinase superfamily. Categories of
      kinases with progressive evolutionary divergence, viz. (i) Same kinase with many
      crystal structures, (ii) Within-Subfamily, (iii) Within-Family, (iv) Within
      Group, and (v) Across-Group, were analyzed. We identified a flexibility signature
      conserved in all kinases involving residues in and around the catalytic loop with
      consistent low-magnitude fluctuations. However, the overall structural
      fluctuation profiles are conserved better in closely related kinases (Within
      Subfamily and Within-family) than in distant ones (Within-Group and Across
      Group). A substantial 65.4% of variation in flexibility was not accounted by
      variation in sequences or structures. Interestingly, we identified substructural
      residue-wise fluctuation patterns characteristic of kinases of different
      categories. Specifically, we recognized statistically significant fluctuations
      unique to families of protein kinase A, cyclin-dependent kinases, and nonreceptor
      tyrosine kinases. These fluctuation signatures localized to sites known to
      participate in protein-protein interactions typical of these kinase families. We
      report for the first time that residues characterized by fluctuations unique to
      the group/family are involved in interactions specific to the group/family. As
      highlighted for Src family, local regions with differential fluctuations are
      proposed as attractive targets for drug design. Overall, our study underscores
      the importance of consideration of fluctuations, over and above sequence and
      structural features, in understanding the roles of sites characteristic of
      kinases. Proteins 2016; 84:957-978. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028939
TI  - Pregabalin prescriptions in the United Kingdom: a drug utilisation study of The
      Health Improvement Network (THIN) primary care database.
AB  - AIM: In Europe, pregabalin is approved for treatment of neuropathic pain, general
      anxiety disorder (GAD) and as adjunctive therapy for epilepsy. The purpose of
      this study was to assess utilisation of pregabalin in the UK, including patients
      with a recorded history of substance abuse, from a large general practice
      database. METHODS: This observational drug utilisation study (DUS) analysed
      pregabalin prescription data from the UK Health Improvement Network primary care
      database between September 2004 and July 2009. Patient demographics, diagnoses
      (by READ codes) and pregabalin dosing data were collected. Diagnosis codes were
      used as proxy for approved indication for pregabalin. RESULT: A cohort of 18,951
      patients was prescribed pregabalin; dosing information was available for 13,480
      (71.1%). Median age of patients was 58 years, and majority were female (60.1%).
      Median (interquartile range) prescribed average daily dose (ADD) of pregabalin
      for all patients was 150.0 (162.5) mg/day; this was highest in patients with
      epilepsy (191.9 mg/day), followed by neuropathic pain (158.0 mg/day) and GAD
      (150.0 mg/day). Only 1.0% (136/13,480) of patients were prescribed an ADD of
      pregabalin over the maximum approved dose of 600 mg/day. Of these, 18.4% (25/136)
      of patients had a history of substance abuse compared with 14.0% (1884/13,480) in
      the full population. CONCLUSION: Data from this DUS indicated that the majority
      of pregabalin prescribing in the UK was consistent with product labelling. The
      proportion of patients with prescribed ADD > 600 mg/day was small and with a
      similar proportion with a history of substance abuse as in the full population.

PMID- 27028940
TI  - Yohimbine hydrochloride ameliorates collagen type-II-induced arthritis targeting
      oxidative stress and inflammatory cytokines in Wistar rats.
AB  - Rheumatoid arthritis (RA) is the most common type of chronic inflammatory disease
      which is triggered by dysfunction in the immune system which in turn affects
      synovial joints. Current treatment of RA with NSAIDs and DMRDs is limited by
      their side effect. As a result, the interest in alternative, well tolerated anti
      inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and
      anti-inflammatory activities underlying the anti-RA effect of Yohimbine
      hydrochloride (YCL) in collagen induced arthritis (CIA) in Wistar rats. The YCL
      was administered at doses of 5 and 10 mg kg-1 body weight once daily for 28 days.
      The effects of treatment in the rats were assessed by biochemical parameter
      (articular elastase, LPO, GSH, catalase, SOD), hematological parameter (ESR, WBC,
      C-reactive protein (CRP), immunohistochemical expression (COX2, TNF-alpha, and NF
      kappaB), and histological changes in joints. YCL showed anti-RA efficacy as it
      significantly reduced articular elastase, LPO and catalase level and ameliorates
      histological changes. This is in addition to its antioxidant efficacy as YCL
      shown a significant increase in GSH and SOD level. Also, YCL showed effective
      anti-inflammatory activity as it significantly decreased the expression of COX-2,
      TNF-alpha, and NF-KB. The therapeutic effect of YCL against RA was also evident
      from lower arthritis scoring and reduced hematological parameter (ESR, WBC, and C
      reactive protein level). The abilities to inhibit proinflammatory cytokines and
      modulation of antioxidant states that the protective effect of YCL on arthritis
      rats might be mediated via the modulation of the immune system. (c) 2016 Wiley
      Periodicals, Inc. Environ Toxicol 32: 619-629, 2017.

PMID- 27028941
TI  - Elucidating Hyperconjugation from Electronegativity to Predict Drug
      Conformational Energy in a High Throughput Manner.
AB  - Computational chemists use structure-based drug design and molecular dynamics of
      drug/protein complexes which require an accurate description of the
      conformational space of drugs. Organic chemists use qualitative chemical
      principles such as the effect of electronegativity on hyperconjugation, the
      impact of steric clashes on stereochemical outcome of reactions, and the
      consequence of resonance on the shape of molecules to rationalize experimental
      observations. While computational chemists speak about electron densities and
      molecular orbitals, organic chemists speak about partial charges and localized
      molecular orbitals. Attempts to reconcile these two parallel approaches such as
      programs for natural bond orbitals and intrinsic atomic orbitals computing Lewis
      structures-like orbitals and reaction mechanism have appeared. In the past, we
      have shown that encoding and quantifying chemistry knowledge and qualitative
      principles can lead to predictive methods. In the same vein, we thought to
      understand the conformational behaviors of molecules and to encode this knowledge
      back into a molecular mechanics tool computing conformational potential energy
      and to develop an alternative to atom types and training of force fields on large
      sets of molecules. Herein, we describe a conceptually new approach to model
      torsion energies based on fundamental chemistry principles. To demonstrate our
      approach, torsional energy parameters were derived on-the-fly from atomic
      properties. When the torsional energy terms implemented in GAFF, Parm@Frosst, and
      MMFF94 were substituted by our method, the accuracy of these force fields to
      reproduce MP2-derived torsional energy profiles and their transferability to a
      variety of functional groups and drug fragments were overall improved. In
      addition, our method did not rely on atom types and consequently did not suffer
      from poor automated atom type assignments.

PMID- 27028942
TI  - Massive Gastrointestinal Bleed as Presentation for Previously Undiagnosed
      Coarctation of Aorta.
AB  - BACKGROUND: Coarctation of the aorta is a common congenital heart lesion with a
      known complication of collateral vessel formation if left untreated. OBJECTIVE:
      To alert pediatric emergency physicians of a rare and life-threatening
      presentation of previously undiagnosed congenital heart disease in the
      adolescent. CASE: We discuss the case of a 15-year-old boy who presented with
      hypertension and massive upper GI bleed due to aortoenteric fistula formation
      associated with undiagnosed coarctation of the aorta. There are no other reports
      of a similar presentation in the literature.

PMID- 27028943
TI  - Nonsteroidal Anti-Inflammatory Drug Toxicity in Children: A Clinical Review.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used
      classes of medications in children. Despite a reported positive safety profile,
      NSAIDs have been associated with toxicities in both overdose and routine use.
      Most children with NSAID overdoses are asymptomatic and should be managed
      conservatively, whereas a small number may present with severe symptoms. We
      review NSAID exposures in children and strategies for their clinical evaluation
      and management. 

PMID- 27028945
TI  - Pediatric Emergency Medicine: Legal Briefs.

PMID- 27028946
TI  - Pediatric Emergency Medicine Fellowship Programs.

PMID- 27028947
TI  - ECGs in the ED.

PMID- 27028948
TI  - Colloids for Management of Dengue and Malaria With Neurological Involvement.

PMID- 27028949
TI  - Treatment of Diabetic Ketoacidosis.

PMID- 27028950
TI  - Tolvaptan is successful in treating inappropriate antidiuretic hormone secretion
      in infants.
AB  - AIM: Using fluid restriction to treat the syndrome of inappropriate antidiuretic
      hormone secretion (SIADH) in infants is potentially hazardous, as fluid intake
      and caloric intake are connected. Antagonists for the type 2 vasopressin receptor
      have demonstrated efficacy in adult patients with SIADH, but evidence in children
      is lacking. We reviewed our experience from two cases in the UK. METHODS: This
      was a retrospective review of the clinical data on two patients diagnosed with
      SIADH in infancy and treated with tolvaptan, an oral vasopressin receptor
      antagonist. RESULTS: Persistent hyponatraemia was noted in both patients in the
      first month of life and eventually led to SIADH diagnoses. Initial salt
      supplementation in one patient resulted in severe hypertension, treated with four
      antihypertensive drugs. Tolvaptan was commenced at two and four months of age,
      respectively, and was associated with normalisation of plasma sodium values and
      blood pressure without the need for antihypertensive treatment. There was
      transient hypernatraemia in one patient, which was normalised with a dose
      reduction. Tolvaptan was administered by crushing the tablet and mixing it with
      water. CONCLUSION: Tolvaptan provided effective treatment for SIADH in both
      infants and could be administered orally.

PMID- 27028951
TI  - A Study of the Carbohydrate-to-Insulin Ratio in Pregnant Women with Type 1
      Diabetes on Pump Treatment.
AB  - AIM: The aim of this study was to assess carbohydrate (CHO)-to-insulin ratio
      (CHO/IR) values in pregnant women with type 1 diabetes and to describe
      differences in CHO/IR across each week of pregnancy. MATERIALS AND METHODS: This
      was a multicenter, retrospective, observational study (2006-2012) of 101 white
      pregnant women with a mean age of 32 (range, 18-43) years who had type 1 diabetes
      and were under continuous subcutaneous insulin infusion (CSII) therapy. These
      patients had the following characteristics: type 1 diabetes duration was 1 year
      (range, 1-31 years), the pregestational glycosylated hemoglobin level was 6.9%
      (range, 6.8-12.1%), the median weight gain during pregnancy was 14 kg (-3; 25
      kg), with delivery at 37 weeks (range, 30-40 weeks), and the child had a birth
      weight of 3.530 kg (range, 1.480-5.250 kg). The CHO/IR was measured by dividing
      the CHO (in g) of each meal by insulin unit injected to acquire and maintain the
      following glycemic targets: fasting <90 mg/dL and 1-h postprandial <130 mg/dL.
      Simultaneously, CHO/IR indices were calculated through 500/total daily doses of
      insulin and 300/total daily doses of insulin. Education and management before and
      during pregnancy were in agreement with Italian Association of Dietitians,
      Association of Medical Diabetologists, and Italian Society of Diabetology
      recommendations. Data were analyzed using SPSS software (version 20.0; SPSS,
      Inc., Chicago, IL). RESULTS: The CHO/IR decreased on average from 9.6 (5-18) to
      5.4 (2.3-8) at breakfast, from 10 (3.5-16) to 8.4 (3.0-17.8) at lunch, and from
      12.5 (8-20) to 6.1 (4.2-12) at dinner. The CHO/IR calculated using the "500 rule"
      decreased from 14.3 (10-20.3) to 8.6 (4.1-15.9). Using the "300 rule," the ratios
      decreased from 8.5 (6-12.1) to 5.2 (2.4-9.5). The bivariate correlation between
      the values calculated more appropriate values using the "300 rule" for breakfast
      and the "500 rule" for lunch and dinner across all weeks of pregnancy.
      CONCLUSIONS: CHO/IR reduction in pregnancy is likely due to an increase in
      insulin resistance.

PMID- 27028952
TI  - Derivation of a formula describing the saturation correction of plane-parallel
      ionization chambers in pulsed fields with arbitrary repetition rate.
AB  - Gas-filled ionization chambers are widely used radiation detectors in
      radiotherapy. A quantitative description and correction of the recombination
      effects exists for two cases, for continuous radiation exposure and for pulsed
      radiation fields with short single pulses. This work gives a derivation of a
      formula for pulsed beams with arbitrary pulse rate for which the prerequisites of
      the two existing descriptions are not fulfilled. Furthermore, an extension of the
      validity of the two known cases is investigated. The temporal evolution of
      idealized charge density distributions within a plane parallel chamber volume is
      described for pulsed beams of vanishing pulse duration and arbitrary pulse
      repetition rate. First, the radiation induced release, movement and collection of
      the charge carriers without recombination are considered. Then, charge
      recombination is calculated basing on these simplified charge distributions and
      the time dependent spatial overlap of positive and negative charge carrier
      distributions. Finally, a formula for the calculation of the saturation
      correction factor is derived by calculation and simplification of the first two
      terms of a Taylor expansion for small recombination. The new formula of
      saturation correction contains the two existing cases, descriptions for exposure
      by single pulses and continuous irradiation, as limiting cases. Furthermore, it
      is possible to determine the pulse rate range for which each of the three
      descriptions is applicable by comparing the dependencies of the new formula with
      the two existing cases. As long as the time between two pulses is lower than one
      third of the collection time of the chamber, the formalism for a continuous
      exposure can be used. The known description for single pulse irradiation is only
      valid if the repetition rate is less than 1.2 times the inverse collection time.
      For all other repetition rates in between the new formula should be used. The
      experimental determination by Jaffe diagrams can be applied for all repetition
      rates which are not single pulse irradiation but will result in a small deviation
      from the correct saturation correction value.

PMID- 27028953
TI  - Circulating miR155 expression level is positive with blood pressure parameters:
      Potential markers of target-organ damage.
AB  - OBJECTIVES: The aim of this study is to evaluate the relationship of miR155 with
      office and ambulatory blood pressure (BP) parameters and left ventricular
      hypertrophy (LVH) in patients with hypertension and healthy controls. METHODS: We
      assessed the expression level of the miR155 in 50 patients with essential
      hypertension and 30 healthy individuals. All patients underwent two-dimensional
      echocardiography, office BP monitoring and ambulatory blood pressure monitoring
      (ABPM). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)
      was used to evaluate the expression of selected miR155. The miR155 correlations
      between BP parameters and left ventricular mass index (LVMI) were assessed using
      the Spearman correlation coefficient. RESULTS: We observed higher expression
      level of miR155 (33.22 +/- 2.59 vs. 27.30 +/- 1.76; p < 0.001) in hypertensive
      patients compared with healthy control individuals, as well as in LVH to nLVH
      group (33.00 +/- 2.78 vs. 27.28 +/- 1.76; p < 0.001). MiR155 expression level
      showed significant positive correlations with office measurement of systolic
      blood pressure (SBP) (r = 0.634, p < 0.001), diastolic blood pressure (DBP) (r =
      0.222, p < 0.05), pulse pressure (PP) (r = 0.564, p < 0.001), respectively. And
      explored miR155 expression level in relation to 24-h ABPM parameters showed
      significant positive correlation with 24 h mean SBP (r = 0.67, p < 0.001), 24 h
      mean DBP (r = 0.257, p < 0.05), 24 h mean PP (r = 0.597, p < 0.001),
      respectively, as well as with LVMI (r = 0.591, p < 0.001). CONCLUSION:
      Circulating miR155 may possibly represent potential non-invasive marker of
      hypertension and target organ damage (TOD) in essential hypertensive patients.

PMID- 27028954
TI  - Oral health services within community-based organizations for young children with
      special health care needs.
AB  - PURPOSE: To identify the types of oral health services offered by community-based
      organizations to young children with special health care needs (CSHCN) and the
      barriers and facilitators to the provision of these in a nonfluoridated
      community. METHODS: Thirteen key informant interviews with representatives from
      early intervention agencies, advocacy groups, and oral health programs who
      provide services to CSHCN in Spokane county, Washington. We used a content
      analysis to thematically identify oral health services as proactive or incidental
      and the barriers and facilitators to their provision. RESULTS: We identified four
      types of oral health services: screenings, parent education, preventive dental
      care, and dental referrals. Barriers to providing all four services included
      limited agency resources, restrictive administrative and system-level policies,
      and low demand from parents. A barrier to providing education and preventive
      dental care was community disagreement regarding fluoride. A barrier to providing
      dental referrals was the perceived lack of dentists who could treat CSHCN.
      Facilitators included community partnerships among the organizations and
      utilization of the statewide oral health program. CONCLUSIONS: Oral health
      services for young CSHCN are limited and often delivered in response to oral
      health problems. Coordinated efforts between community-based organizations,
      health providers, and advocates are necessary to ensure the provision of
      comprehensive care, including preventive and restorative services, to all young
      CSHCN.

PMID- 27028956
TI  - Addendum.

PMID- 27028955
TI  - Brain structural connectivity distinguishes patients at risk for cognitive
      decline after carotid interventions.
AB  - While brain connectivity analyses have been demonstrated to identify ill patients
      for a number of diseases, their ability to predict cognitive impairment after
      brain injury is not well established. Traditional post brain injury models, such
      as stroke, are limited for this evaluation because pre-injury brain connectivity
      patterns are infrequently available. Patients with severe carotid stenosis, in
      contrast, often undergo non-emergent revascularization surgery, allowing the
      collection of pre and post-operative imaging, may experience brain insult due to
      perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post
      operative cognitive decline. We hypothesized that a distributed function such as
      memory would be more resilient in patients with brains demonstrating higher
      degrees of modularity. To test this hypothesis, we analyzed preoperative
      structural connectivity graphs (using T1 and DWI MRI) for 34 patients that
      underwent carotid intervention, and evaluated differences in graph metrics using
      the Brain Connectivity Toolbox. We found that patients with lower binary
      component number, binary community number and weighted community number prior to
      surgery were at greater risk for developing cognitive decline. These findings
      highlight the promise of brain connectivity analyses to predict cognitive decline
      following brain injury and serve as a clinical decision support tool. Hum Brain
      Mapp 37:2185-2194, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27028957
TI  - Somatostatin Analogs and Tumor Localization Do Not Influence Vitamin D
      Concentration in Patients with Neuroendocrine Tumors.
AB  - Patients with neuroendocrine tumors (NETs), malignancies of rare but still rising
      incidence, may be a group at higher risk of vitamin D insufficiency. The
      gastrointestinal tumor prevalence and somatostatin analog (SSA) therapy may cause
      vitamin D malabsorption. The aim of this study was to evaluate the serum level of
      vitamin D in NET patients. A total of 36 NET patients were enrolled into the
      experimental group and 16 individuals were enrolled into the control group. All
      patients were further classified into subgroups according to primary tumor
      localization (gastropancreatic, lung, and other NETs) or therapy (with or without
      SSA treatment). The concentrations of total 25(OH)D were assayed with
      Electrochemiluminescence immunoassay (ECLIA). Serum concentration of 25(OH)D in
      NET patients did not differ significantly from that of the control group.
      However, the average level of 25(OH)D in both groups met the criteria of vitamin
      D deficiency. Importantly, SSA therapy did not aggravate vitamin D deficiency.
      Moreover, the concentration of 25(OH)D in the studied group was not significantly
      influenced by primary tumor localization, patient age, or season. Vitamin D
      deficiency is a widespread disorder affecting both NET patients and individuals
      without other health problems, and SSA and gastrointestinal tumor localization do
      not exacerbate this condition. 

PMID- 27028959
TI  - Towards an agreed quality standard for rental housing: field testing of a New
      Zealand housing WOF tool.
AB  - OBJECTIVE: Report on a field test of a rental housing warrant of fitness (WOF) to
      assess its practicality and utility for supporting improved quality of housing.
      METHODS: Five councils each recruited at least 25 rental houses to undergo a WOF
      assessment. The assessment included housing features that, based on a combination
      of research and practicality, were considered to have an important impact on
      health, safety and energy efficiency. Assessors were interviewed to get their
      feedback on the process. Landlords representing 81% of the rental properties were
      interviewed on their attitudes to the WOF. RESULTS: Of the sample of 144 houses,
      94% failed at least one of 31 criteria. The most common reasons were: unsafe
      water temperature; no security stays; no smoke alarms; no fixed heating; and
      unsuitable handrails/balustrades. If items that required little (<NZ$100) or no
      financial cost were fixed, 44 extra houses (36%) would have passed. CONCLUSIONS:
      All WOF items could be checked in a variety of dwellings. The houses had numerous
      health and safety defects, many of which could be rectified relatively easily at
      a low cost. IMPLICATIONS: Implementing a rental housing WOF on a national scale
      has potential to improve the health and safety of tenants, as well as making
      energy efficiency gains. Future decisions on how to intervene to protect health
      and safety will be informed by data collected.

PMID- 27028958
TI  - Respiratory modulation of human autonomic function on Earth.
AB  - KEY POINTS: We studied healthy supine astronauts on Earth with electrocardiogram,
      non-invasive arterial pressure, respiratory carbon dioxide concentrations,
      breathing depth and sympathetic nerve recordings. The null hypotheses were that
      heart beat interval fluctuations at usual breathing frequencies are baroreflex
      mediated, that they persist during apnoea, and that autonomic responses to apnoea
      result from changes of chemoreceptor, baroreceptor or lung stretch receptor
      inputs. R-R interval fluctuations at usual breathing frequencies are unlikely to
      be baroreflex mediated, and disappear during apnoea. The subjects' responses to
      apnoea could not be attributed to changes of central chemoreceptor activity
      (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex
      gain declined and muscle sympathetic nerve burst areas, frequencies and
      probabilities increased, even as arterial pressure climbed to new levels); or
      altered pulmonary stretch receptor activity (major breathing frequency and tidal
      volume changes did not alter vagal tone or sympathetic activity). Apnoea
      responses of healthy subjects may result from changes of central respiratory
      motoneurone activity. ABSTRACT: We studied eight healthy, supine astronauts on
      Earth, who followed a simple protocol: they breathed at fixed or random
      frequencies, hyperventilated and then stopped breathing, as a means to modulate
      and expose to view important, but obscure central neurophysiological mechanisms.
      Our recordings included the electrocardiogram, finger photoplethysmographic
      arterial pressure, tidal volume, respiratory carbon dioxide concentrations and
      peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and
      muscle sympathetic outflow were comparable during spontaneous and controlled
      frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing,
      however, breathing at usual frequencies (~0.25 Hz) lowered arterial baroreflex
      gain, and provoked smaller arterial pressure and R-R interval fluctuations, which
      were separated by intervals that were likely to be too short and variable to be
      attributed to baroreflex physiology. R-R interval fluctuations at usual breathing
      frequencies disappear during apnoea, and thus cannot provide evidence for the
      existence of a central respiratory oscillation. Apnoea sets in motion a
      continuous and ever changing reorganization of the relations among stimulatory
      and inhibitory inputs and autonomic outputs, which, in our study, could not be
      attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor
      activity. We suggest that responses of healthy subjects to apnoea are driven
      importantly, and possibly prepotently, by changes of central respiratory
      motoneurone activity. The companion article extends these observations and asks
      the question, Might terrestrial responses to our 20 min breathing protocol find
      expression as long-term neuroplasticity in serial measurements made over 20 days
      during and following space travel?

PMID- 27028961
TI  - Comprehensive review of telbivudine in pregnant women with chronic hepatitis B.
AB  - AIM: To achieve an evidence-based conclusion regarding the safety and efficacy of
      telbivudine during pregnancy. METHODS: A pooled analysis of data from a
      literature search reported 1739 pregnancy outcomes (1673 live births) from 1725
      non-overlapping pregnant women treated with telbivudine. The prevalence of live
      birth defects (3.6/1000) was similar to that of the non-antiviral controls
      (3.0/1000) and not increased as compared with overall prevalence (14.5 to
      60/1000). No target organ toxicity was identified. The prevalence of spontaneous
      abortion in pregnant women treated with telbivudine (4.2/1000) was not increased
      compared with the overall prevalence (16/1000). The mother-to-child transmission
      rate was significantly reduced in pregnant women treated with telbivudine (0.70%)
      compared to those treated with the non-antiviral controls (11.9%; P < 0.0001) or
      compared to the historical rates of hepatitis B virus (HBV)-infected population
      without antiviral treatment (10%-15%). RESULTS: Cumulatively 489 pregnancy cases
      have been reported in the telbivudine pharmacovigilance database (with a cut-off
      date 31 August 2014), of those, 308 had known pregnancy outcomes with 249 cases
      of live births (239 cases of live birth without congenital anomaly and 10 cases
      of live birth with congenital anomaly). In the latest antiretroviral pregnancy
      registry report (1 January 1989 through 31 January 2015) of 27 patients exposed
      to telbivudine during pregnancy (18, 6 and 3 during first, second and third
      trimester, respectively) 19 live births were reported and there were no cases of
      birth defects reported. CONCLUSION: Telbivudine treatment during pregnancy
      presents a favorable safety profile without increased rates of live birth
      defects, spontaneous abortion or elective termination, or fetal/neonatal
      toxicity. Exposure to telbivudine in the first, second and third trimester of
      pregnancy has been shown to significantly reduce the risk of HBV transmission
      from mother to child on the basis of standard immune prophylaxis procedure.

PMID- 27028960
TI  - Nonoccupational exposure to agricultural work and risk of urinary bladder cancer
      among Egyptian women.
AB  - This study examined the associations between nonoccupational exposure to
      agricultural work, through husband or head of household (H/HH) occupation, and
      urinary bladder cancer risk among Egyptian women. A total of 1,167 women (388
      bladder cases and 779 age- and residence-matched, population-based controls) from
      a multicenter case-control study were included in the analysis. Adjusted odds
      ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic
      regression. Among married women, those who reported H/HH to be an agricultural
      worker were at increased risk for bladder cancer as compared to those with H/HH
      in other occupations, AOR = 1.54, 95% CI [1.09, 2.18]; among unmarried women the
      risk was not increased, AOR = 0.77, 95% CI [0.45, 1.32]. Nonoccupational exposure
      to agricultural work, defined as living with an agricultural worker, increased
      the risk for bladder cancer among married Egyptian women.

PMID- 27028966
TI  - Efficacy of Long-Acting Injectable Antipsychotics in Adolescents.
AB  - INTRODUCTION: The number of long-acting injectable antipsychotics (LAIA) has
      increased in recent years. The safety and efficacy of that treatment are not
      established in children. This study aims to address this gap of information by
      studying such treatments in a case series. METHODS: This retrospective chart
      review of patients identified by the investigators at an academic acute inpatient
      psychiatric unit included all patients from the past 24 months who required new
      initial treatment with LAIA. This study included a case series of the nine
      patients along with Clinical Global Impression-Severity (CGI-S) scores from
      admission and discharge and Clinical Global Impression-Improvement (CGI-I)
      scores. Other observations included the presentation of primary psychiatric
      diagnosis, psychiatric and medical comorbidities, age, sex, previous and LAIA
      psychiatric medications, reasoning for LAIA treatment, adverse events, CGI-S and
      CGI-I scores, and outpatient resources utilized to continue treatment. RESULTS:
      The case series included two females and seven males within the ages of 14-17
      years. Of those patients, five were treated with paliperidone palmitate, one
      treated with risperidone, one treated with fluphenazine, and one treated with
      aripiprazole. Primary psychiatric diagnosis of the patients in the case series
      included five with schizophrenia, one with schizoaffective disorder, one with
      bipolar affective disorder-type I, one with bipolar affective disorder-not
      otherwise specified, and one with mood disorder-not otherwise specified. In all
      nine cases, noncompliance was a consideration in treatment with LAIA. Frequent
      running away and severity of illness were also considerations in one case each.
      All of the patients required community resources with injectable services.
      CONCLUSION: This study describes initiation of treatment with LAIA in 14-17-year
      olds in an acute inpatient psychiatric unit with serious mental illness. This
      study also demonstrates the need for outpatient community resources with the
      ability to provide long-acting injectable medication. Limitations of this study
      include a small patient population, other factors changing CGI-S and CGI-I scores
      beyond the medication, and the nature of the study as a retrospective chart
      review. This study did not compare medications between each other. Maintenance
      dosing and long-term safety were beyond the scope of this study. Future
      directives for safety studies, open-label trials, and randomized double-blinded
      control trails in the pediatric population would be needed.

PMID- 27028967
TI  - Recovery from major depressive disorder episode after non-pharmacological
      treatment is associated with normalized cytokine levels.
AB  - BACKGROUND: Several lines of evidence show that the immune system is implicated
      in the pathophysiology of major depressive disorder (MDD) and that treatment with
      antidepressants affects cytokine and C-reactive protein (CRP) levels. Few studies
      have investigated immune markers during non-pharmacological treatment. In this
      follow-up study, we investigated whether CRP and elevated plasma cytokine levels
      observed before treatment of an acute episode of MDD are normalized during non
      pharmacological treatment. METHODS: We obtained clinical assessments and blood
      for CRP and cytokine analysis from 50 unmedicated MDD patients, and cytokine
      levels from healthy controls. The patients received 'therapy as usual' for 12
      weeks, and the assessments were then repeated. Of the 43 completers, 29 patients
      did not receive medication. RESULTS: In the patients receiving treatment without
      antidepressants, the depressive symptoms and the plasma levels of eight cytokines
      (interleukin (IL)-1Ra, IL-5,-6,-8,-10, G-CSF, IFN-gamma, and TNF-alpha) were
      significantly reduced (P = 0.002-0.048). The cytokine levels were no longer
      different from the controls. The plasma CRP level did not change. CONCLUSION:
      Cytokine plasma levels normalized during recovery from an acute depressive
      episode in MDD without antidepressant treatment. These findings may have
      implications for the understanding of the role of the immune system in depression
      and recovery from depression.

PMID- 27028968
TI  - What is the Current Role of Immunotherapy for Colon Cancer?
AB  - Colon cancer is a leading cause of cancer related mortality. Until very recently
      the only existing options that medical oncologists had to treat metastatic colon
      cancer were a combination of chemotherapy, anti-EGFR and anti-angiogenic agents.
      We currently have the first proof that immune therapies could be an effective
      approach to battle colorectal cancers that carry a mismatch repair machinery
      deficient phenotype. It is expected that as our knowledge of the different
      mechanisms of immune-resistance grows, this therapeutic modality might soon be
      applicable to all patients. However, due to the continuous increase in the cost
      of oncological drugs, some treatment overheads may soon become prohibitive for
      many. In this review we will examine the current evidence related to this topic
      with the objective to provide the reader with concise but practical information
      about the potential role of immunotherapy in CRC.

PMID- 27028969
TI  - Immunotherapy for Non-Small Cell Lung Cancer - Finally a Hint of Hope.
AB  - Lung cancer is a major public health problem worldwide and the leading cause of
      cancerrelated mortality in developed countries. Significant advances have been
      made especially with the discovery of targeted agents. However, only a small
      proportion of patients carry activating mutations; until recently conventional
      chemotherapy and angiogenesis inhibitors were the preferred treatment for the
      vast majority of patients. Now, the successful experience of anti-PD-1 agents may
      have opened the door to a novel and previously unexplored dimension in the
      treatment of lung cancer: immunotherapy. In this mini-review we will discuss the
      current applications and future consequences related this topic, paying special
      attention to the clinical studies that constitute the scientific evidence to
      supports its use.

PMID- 27028970
TI  - Immune Check Point Inhibitors Combination in Melanoma: Worth the Toxicity?
AB  - The combination of immune checkpoint inhibitors ipilimumab and nivolumab has been
      recently been FDA approved for first line treatment of unresectable and
      metastatic BRAF wild type melanoma. The approval came following the impressive
      results of the CheckMate 067, where the combination of ipilimumab and nivolumab
      appeared to outperform each as a single agent in regards to response rate and
      progression free survival. Though we await final overall survival data, the
      combination will likely be adapted by many oncologists and integrated into the
      ever changing melanoma treatment algorithm. In this article we aim to summarize
      the data leading up to the recent FDA approval and publication by Larkin et al.
      that presents the results from the CheckMate 067 trial. We will also further
      explore the feasibility, challenges, and applicability of combination immune
      checkpoint inhibitor therapy.

PMID- 27028971
TI  - Overcoming Resistance to EGFR Inhibitors in NSCLC.
AB  - BACKGROUND: The clarification of several molecular pathways underlying the
      tumorigenesis has led to the development of several targeted drugs that have
      substantially improved the treatment of Non-Small-Cell Lung Cancer (NSCLC). The
      Epidermal Growth Factor Receptor (EGFR) is the target of several Tyrosine-Kinase
      Inhibitors (TKIs), some of them approved for treatment and others currently in
      clinical development. EGFR-TKIs markedly improve progression-free survival of
      patients with advanced NSCLC with EGFR mutations compared with chemotherapy.
      METHODS: We undertook a structured search of bibliographic databases for peer
      reviewed research literature using a focused review question. RESULTS: Although
      first- and second-generation agents offer in target population (with EGFR
      mutations) a substantial improvement of outcomes compared with standard
      chemotherapy, unfortunately, drug resistance develops after initial benefit,
      through a variety of mechanisms. Novel- (third) generation EGFR inhibitors have a
      selective mechanism of action and are currently in advanced clinical development,
      producing encouraging results in patients with acquired resistance to previous
      generation agents. CONCLUSION: The search for new drugs or strategies to overcome
      the TKI resistance in patients with EGFR mutations is to be considered a priority
      for the improvement of outcomes in the treatment of advanced NSCLC, and third
      generation EGFR inhibitors are the most promising approach to the issue.

PMID- 27028972
TI  - To Be-et, or Not to Be-et, That is the Question: The Role(s) of Nitrate and
      Nitrite in Health and Illness.
AB  - BACKGROUND: This manuscript addresses the multilevel role of dietary nitrate and
      nitrite in health and diseases because of increased interest in dietary
      supplementation. METHOD: Review of research devoted to both beneficial but also
      possible deleterious effects of uncontrolled indigestion of red beet-root juice
      and other sources of high concentrated nitrate and nitrite. RESULTS: The body of
      evidence strongly suggested that persons using nitrate/nitrite supplementation
      and particularly patients treated with sodium nitrite, having kidney disease or
      impaired methemoglobin reeducates activity, should closely monitor
      nitrate/nitrite indigestion. CONCLUSION: Oral intake of red beet-root juice,
      green leaved veggies, cured meat, as well as urine excretion of nitrate/ nitrite,
      methemoglobin reeducates activity should be carefully assessed especially in
      patients treated with sodium nitrite.

PMID- 27028973
TI  - Quantitative assessment of the effect of position changes during colonoscopy
      withdrawal.
AB  - OBJECTIVE: Although trials assessing the effectiveness of position changes during
      colonoscopy withdrawal have been reported, there has been no agreement whether
      such position changes actually improve the polyp detection rate (PDR) or adenoma
      detection rate (ADR). This article aimed to address this issue by performing a
      systematic review. METHODS: Relevant studies from databases including PubMed,
      EMBASE and the Cochrane Library and Science Citation Index were retrieved. Two
      reviewers independently identified potentially relevant studies. Outcome measures
      were PDR, ADR and bowel distention. RESULTS: Eight studies were included, of
      which seven were randomized controlled trials (RCTs). A non-randomized controlled
      trial and all four cross-over RCTs reported significant improvement in PDR, ADR
      and bowel distention with position change during colonoscopic withdrawal, while
      three parallel-group RCTs did not confirm its effectiveness. CONCLUSIONS: The
      conflicting results of high-quality trials indicate that the effectiveness of
      position change during colonoscopy withdrawal on PDR, ADR and bowel distension is
      uncertain. Thus, position change during colonoscopy withdrawal should not be
      routinely applied until future studies demonstrate its efficacy.

PMID- 27028974
TI  - Intentional rounding: facilitators, benefits and barriers.
AB  - AIMS AND OBJECTIVES: To describe the implementation, practice and sustainability
      of Intentional Rounding (IR) within two diverse settings (aged care and
      maternity). BACKGROUND: The profile of patients in hospitals has changed over
      time, generally being more severe, placing heavy demands on nurses' time. Routine
      non-urgent care is often provided only when there is time. IR has been found to
      increase both patient and staff satisfaction, also resulting in improved patient
      outcomes such as reduced falls and call bell use. IR is also used as a time
      management tool for safe and reliable provision of routine care. METHODS: This
      descriptive qualitative research study comprised of three focus groups in a
      metropolitan hospital. RESULTS: Fifteen nurses participated in three focus
      groups. Seven main themes emerged from the thematic analysis of the verbatim
      transcripts: implementation and maintenance, how IR works, roles and
      responsibilities, context and environment, benefits, barriers and legal issues.
      CONCLUSION: IR was quickly incorporated into normal practice, with clinicians
      being able to describe the main concepts and practices. IR was seen as a
      management tool, facilitating accountability and continuity of management support
      being essential for sustainability. Clinicians reported increases in patient and
      staff satisfaction, and the opportunity to provide patient education. While
      patient type and acuity, ward layout and staff experience affected the practice
      of IR, the principles of IR are robust enough to allow for differences in the
      ward specialty and patient type. However, care must be taken when implementing IR
      to reduce the risk of alienating experienced staff. Incorporation of IR charts
      into the patient health care record is recommended. RELEVANCE TO CLINICAL
      PRACTICE: Engaging all staff, encouraging ownership and stability of management
      are key factors in the successful implementation and maintenance of IR. IR is
      flexible and robust enough to accommodate different patient types and acuity.

PMID- 27028975
TI  - 3-octadecylcarbamoylacrylic acid-cisplatin nanocomplexes for the development of
      novel liposome formulation.
AB  - It was the first time that 3-octadecylcarbamoylacrylicacid-cisplatin
      nanocomplexes (OMI-CDDP-N) were synthesized via monocarboxylato and O->Pt
      coordination. The nanocomplexes exhibited lower IC50 values compared with
      cisplatin (CDDP) in vitro, and enhanced antitumor efficacy in murine liver cancer
      (H22) in vivo. However, the toxicity of the nanocomplexes was more severe than
      CDDP. OMI-CDDP-N-based liposome (OCP-L) was prepared in order to maintain the
      efficacy and reduce the toxicity of OMI-CDDP-N. Here, a series of parameters were
      investigated to optimize liposome formulation. The optimal formulation was
      CDDP/phospholipids/cholesterol (1/10/0.7 wt.%), with distilled water as hydration
      medium and an encapsulation efficiency of 94.2 +/- 2.1%. In vitro cytotoxicity
      studies revealed that OCP-L and OMI-CDDP-N exhibited a lower IC50 compared with
      commercial cisplatin injection (CDDP-S) in a variety of human cancer cells. In
      H22-implanted mice, OCP-L showed a significantly higher antitumor activity than
      OMI-CDDP-N or CDDP-S at a dose of 5 mg/kg (p < 0.01). Moreover, OCP-L exceeded
      the size cutoff for kidney clearance, hence it bypassed the nephrotoxicity of
      CDDP which is a major curse of CDDP in the clinic. These results suggested that
      the unique OMI-CDDP-N-entrapped liposome can overcome the disadvantages
      associated with conventional CDDP therapy and provide a higher safety profile.

PMID- 27028976
TI  - Garden greenery and the health of older people in residential care facilities: a
      multi-level cross-sectional study.
AB  - AIMS: To test the relationship between greenery in gardens at residential
      facilities for older people and the self-perceived health of residents, mediated
      by experiences of being away and fascination when in the garden and the frequency
      of visitation there. To examine how these indirect effects vary with the number
      of physical barriers to visiting the garden. BACKGROUND: Many older people in
      residential facilities suffer from complex health problems. Access to a green
      outdoor environment may enable psychological distance, engage effortless
      attention, encourage more frequent visitation and promote resident health.
      DESIGN: A multi-level, cross-sectional, correlational design. METHODS:
      Questionnaires were administered June-August, 2011 to convenience samples of
      residents at 72 facilities for older people with complex healthcare needs. One to
      10 eligible residents were sampled during self-motivated garden visits at each
      facility (n = 290). They reported on their garden experiences and health.
      Facility staff reported on objective garden characteristics and barriers to
      access. A serial mediation model was tested with multiple linear regression
      analysis. RESULTS: The total indirect effect of greenery on self-perceived health
      was positive and significant. Garden greenery appears to affect health by
      enhancing a sense of being away, affording possibilities to experience the
      outdoor environment as interesting and encouraging visitation. Among residents in
      homes with multiple barriers, only fascination mediated the relationship between
      greenery and self-perceived health. CONCLUSION: Ample greenery in outdoor space
      at residential facilities for older people appears to promote experiences of
      being away and fascination, more frequent visitation and better health.

PMID- 27028977
TI  - Phosphate-induced fluorescence of a tetraphenylethene-substituted tripodal
      tris(urea) receptor.
AB  - A tetraphenylethene (TPE)-decorated tripodal tris(urea) ligand was synthesized,
      which shows large emission enhancement when binding to an orthophosphate anion
      (PO4(3-)), but exhibits only weak or no fluorescence with other anions. The anion
      binding and fluorescence properties were studied by X-ray crystal structure, NMR
      and fluorescence spectroscopy, and by DFT computations and the results
      demonstrate that the different fluorescence performance may be determined by the
      anion-binding modes (i.e., full- or half-encapsulation).

PMID- 27028978
TI  - Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism
      in fungal disease.
AB  - Intracellular swelling of conidia of the major human airborne fungal pathogen
      Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen
      associated molecular patterns (PAMPs) and triggers activation of a specialized
      autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal
      killing. We have recently discovered that, apart from PAMPs exposure, cell wall
      melanin removal during germination of A. fumigatus is a prerequisite for
      activation of LAP. Importantly, melanin promotes fungal pathogenicity via
      targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence
      upon conditional inactivation of Atg5 in hematopoietic cells of mice.
      Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox
      subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering
      with signaling regulating cytokine responses. Notably, inhibition of LAP is a
      general property of melanin pigments, a finding with broad physiological
      implications.

PMID- 27028979
TI  - Patient knowledge and expectations in endoscopic sinus surgery.
AB  - BACKGROUND: The potential for patient misconceptions about endoscopic sinus
      surgery (ESS) has implications for the informed consent process. An understanding
      of patients' baseline knowledge and sources of information regarding ESS would
      improve surgeons' ability to counsel patients preoperatively and provide
      effective educational materials. METHODS: A prospective patient survey was
      performed at 2 independent tertiary care medical centers. Patients who were
      offered ESS as part of routine rhinology care were queried about expectations,
      knowledge, and sources of information regarding ESS before preoperative
      counseling. RESULTS: Of the 30 patients who completed the survey, 70% of patients
      reported doing research on ESS before the visit. The most common sources of
      information were friends and family (40%), YouTube (30.0%), and WebMD (26.7%).
      The most important factors researched included risks (95%), benefits (85%), and
      recovery related issues (70%). Patients in the younger group used healthcare and
      physician rating websites whereas none of the patients older than the median age
      of 44 years reported using them (33.3% vs 0%, p = 0.028). The older group more
      often relied upon healthcare providers than the younger group (71.5% vs 18.8%, p
      = 0.011). A range of responses were noted regarding early postoperative symptoms
      and recovery time. CONCLUSION: This study identified a varied understanding of
      ESS including significant misconceptions about risks, anesthesia, and need for
      ongoing therapy, among others. Patients obtain their information from a variety
      of sources including peers, other doctors, and the Internet. Awareness of the
      gaps in patient knowledge and the sources of information will improve
      preoperative counseling.

PMID- 27028980
TI  - Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for
      Hypersalivation Associated With Clozapine.
AB  - Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of
      clozapine therapy that frequently leads to noncompliance. The aim of this study
      was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic
      medication) as an option for management of hypersalivation associated with
      clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted
      in university-based research clinics from January 2012 to May 2014, on 58
      inpatients treated with clozapine who were experiencing hypersalivation. The
      subjects were randomly divided into placebo and metoclopramide groups. The
      starting dose was 10 mg/d. Participants who did not respond were up-titrated 10
      mg/d weekly to a total of 30 mg/d during the third week. The number of placebo
      capsules was increased accordingly up to 3 capsules per day. Primary outcome was
      the change from baseline to the end of study in the severity of hypersalivation
      as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling
      Severity Scale. Secondary outcomes included Clinical Global Impression of
      Improvement scale and adverse effect scales. Significant improvement on the
      Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide
      group from the end of the second week (P < 0.004), and on the Drooling Severity
      Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale
      scores revealed major improvement. Twenty subjects (66.7%) treated with
      metoclopramide reported significant decline or total disappearance of HAC in
      comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse
      effects to metoclopramide were reported. Metoclopramide was found to be safe and
      effective for the treatment of HAC. 

PMID- 27028981
TI  - A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to
      Counteract Olanzapine-Associated Weight Gain.
AB  - Patients with schizophrenia experience higher rates of obesity and related
      morbidity and mortality than the general population does. Given preclinical
      studies revealing the role of histamine H1 receptor in human eating behavior, and
      the potential of olanzapine to block with this system, we hypothesized that
      histamine H1 receptor agonists may be beneficial in reducing antipsychotic
      associated weight gain. In the present study, 36 patients with a diagnosis of
      schizophrenia or schizoaffective disorder and treated with olanzapine were
      randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study
      outcomes were change in body weight from baseline and effect on antipsychotic
      efficacy of olanzapine. The patients in the betahistine group had less weight
      gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg,
      respectively). Positive and Negative Syndrome Scale Questionnaire showed
      improvement within each group and that subjects treated with betahistine enjoyed
      an improvement (reduction) by a mean of 35.7 points, higher when compared with
      placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal
      amount of subjects in both groups experienced adverse effects during the course
      of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects).
      Overall, there were no clinically marked differences in safety signals between
      both groups. A larger study addressing the weaknesses of this pilot study is
      warranted. 

PMID- 27028982
TI  - Second-Generation Antipsychotics During the Lactation Period: A Comparative
      Systematic Review on Infant Safety.
AB  - OBJECTIVE: This review examined the safety of second-generation antipsychotics
      (SGAs) in exposed breastfed infants. METHODS: PubMed was searched for English
      language reports between January 1, 1990, to June 30, 2015, by using combinations
      of the key words breastfeeding, lactation, postpartum period, puerperium,
      antipsychotics, second-generation antipsychotics, olanzapine, quetiapine,
      risperidone, ziprasidone, aripiprazole, amisulpride, clozapine, asenapine,
      lurasidone, and iloperidone. Case reports, case series, and prospective or cross
      sectional studies including relevant data such as relative infant dose (RID),
      milk-to-plasma ratio (M/P ratio), infant drug plasma levels, and adverse events
      were identified. RESULTS: A total of 37 relevant reports were examined. These
      reports included a total of 206 infants exposed to olanzapine (n = 170),
      quetiapine (n = 14), risperidone/paliperidone (n = 8), clozapine (n = 6),
      aripiprazole (n = 4), ziprasidone (n = 2), and amisulpride (n = 2). Approximately
      half of the available data on the M/P ratio, RID, and infant drug plasma levels
      included olanzapine. Relatively adequate reports suggest that olanzapine has low
      RID values. Limited reports suggest low RID values for quetiapine and
      ziprasidone, moderate RID values for risperidone/paliperidone and aripiprazole,
      and high RID values for amisulpride. Antipsychotic levels were undetectable in
      the plasma of most of the exposed infants. Other than clozapine, adverse events
      were rarely reported in infants exposed to SGAs. CONCLUSIONS: The current data
      suggest that SGAs seem to be relatively safe in the exposed breastfed infants for
      short-term usage. However, additional studies, in particular for antipsychotics
      other than olanzapine, examining short-term and especially long-term effects of
      SGAs on the breastfed infants are required.

PMID- 27028983
TI  - Prospective Memory Impairment in Children with Prenatal Alcohol Exposure.
AB  - BACKGROUND: Prenatal alcohol exposure (PAE) is linked to impaired performance on
      tests of retrospective memory, but prospective memory (PM; the ability to
      remember and act on delayed intentions) has not been examined in alcohol-exposed
      children. We investigated event-based PM in children with heavy PAE and the
      degree to which associations between PAE and PM are influenced by IQ, executive
      functioning (EF), retrospective memory, and attention deficit/hyperactivity
      disorder (ADHD). METHODS: We administered a computerized PM task to 89 children
      (Mage = 11.1 years) whose mothers were recruited prenatally: 29 with fetal
      alcohol syndrome (FAS) or partial FAS (PFAS), 32 nonsyndromal heavily exposed
      (HE), and 28 Controls. We examined effects of diagnostic group, cue focality, and
      task difficulty on PM performance. The association between a continuous measure
      of alcohol exposure and PM performance was also examined after controlling for
      sociodemographic confounders. Mediation of alcohol effects on PM by IQ, EF, and
      retrospective memory scores was assessed as was the effect of ADHD on PM
      performance. RESULTS: Children with FAS/PFAS made more PM errors than either HE
      or Control children. PAE was negatively related to PM performance even after
      adjusting for sociodemographic confounders, EF, and retrospective memory. This
      relation was only partially mediated by IQ. PAE was related to ADHD, but ADHD was
      not related to PM performance. CONCLUSIONS: Fetal alcohol-related impairment in
      event-based PM was seen in children with FAS/PFAS. The effect of PAE on PM was
      not attributable to impaired EF and retrospective memory and was not solely
      attributable to lower IQ. Consistent with previous studies, we found no effect of
      ADHD on event-based PM performance at this age. This is the first study
      documenting PM impairment in children with heavy PAE and identifies a new domain
      of impairment warranting attention in diagnosis and management of fetal alcohol
      spectrum disorders.

PMID- 27028984
TI  - Evidence of mercury biomagnification in the food chain of the cardinal tetra
      Paracheirodon axelrodi (Osteichthyes: Characidae) in the Rio Negro, central
      Amazon, Brazil.
AB  - In this study, nitrogen stable isotope (delta(15) N) and total mercury (THg)
      analyses were conducted on algae, submersed and emergent macrophytes, shrubs and
      trees, Macrobrachium sp. and Paracheirodon axelrodi collected in three streams
      that drain a large interfluvial region in the middle Rio Negro, Amazonas State,
      Brazil. Samples were collected during different hydrological periods over 12
      months in lower stream reaches and their headwaters; the latter being
      characterized by shallow, open-canopy swamps. Additionally, delta(15) N values
      and mercury concentrations of Paracheirodon simulans and Cichla spp. from the
      middle Rio Negro were analysed to demonstrate THg biomagnification in the food
      web. The highest mercury levels of P. axelrodi were found in small individuals,
      which were collected principally in the low water period. The log10 THg-delta(15)
      N relationship of vascular plants and algae, Macrobrachium sp., Paracheirodon
      spp. and Cichla spp. showed significant mercury biomagnification among trophic
      levels, with regression slopes of 0.15 and 0.25 for the entire food web and
      heterotrophs-only food web, respectively. The mean +/- s.d. THg concentrations
      for Macrobrachium sp., P. axelrodi, P. simulans and Cichla spp. were 63.6 +/-
      23.7, 104.5 +/- 40.0, 112.3 +/- 31.4 and 418.5 +/- 188.1 ng g(-1) wet mass,
      respectively. Elevated levels of mercury found in Paracheirodon spp. and top
      predators such as Cichla spp. in a remote area far from anthropogenic inputs
      provide evidence that high mercury concentrations occur naturally in Rio Negro
      aquatic food webs. 

PMID- 27028985
TI  - Dermatology at the forefront - also with regard to actual politics.

PMID- 27028986
TI  - Too (mentally) busy to chill: Cognitive load and inhibitory cues interact to
      moderate triggered displaced aggression.
AB  - Inhibitory information can be expected to reduce triggered displaced aggression
      by signaling the potential for negative consequences as a result of acting
      aggressively. We examined how cognitive load might interfere with these
      aggression-reducing effects of inhibitory cues. Participants (N = 80) were
      randomly assigned to a condition in a 2 (cognitive load: high/low) * 2
      (inhibiting cues: yes/no) between-subjects design. Following procedures in the
      TDA paradigm, participants received an initial provocation from the experimenter
      and a subsequent triggering annoyance from another individual. In the inhibitory
      cue condition, participants were told, before they had the opportunity to
      aggress, that others would learn of their aggressive responses. In the high
      cognitive load condition, participants rehearsed a 10-digit number while
      aggressing. Those in the low cognitive load condition rehearsed a three digit
      number. We found significant main effects of cognitive load and inhibitory cue,
      which were qualified by the expected load * inhibitory cue interaction. Thus,
      inhibitory cues reduced displaced aggression under low-cognitive load. However,
      when participants in the inhibitory cue condition were under cognitive load,
      aggression increased, suggesting that mental busyness interfered with the full
      use of inhibitory information. Aggr. Behav. 42:598-604, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27028987
TI  - Teaching EBP Using Game-Based Learning: Improving the Student Experience.
AB  - BACKGROUND: Evidence-based practice (EBP) is considered a key entry to practice
      competency for nurses. However, many baccalaureate nursing programs continue to
      teach "traditional" nursing research courses that fail to address many of the
      critical knowledge, skills, and attitudes that foster EBP. Traditional classroom
      teaching strategies do little to promote the development of competencies critical
      for engaging in EBP in clinical contexts. PURPOSE AND GOALS: The purpose of this
      work was to develop, implement, and evaluate an innovative teaching strategy
      aimed at improving student learning, engagement and satisfaction in an online EBP
      course. The goals of this paper are to: (1) describe the process of course
      development, (2) describe the innovative teaching strategy, and (3) discuss the
      outcomes of the pilot course offered using game-based learning. METHODS: A
      midterm course-specific survey and standard institutional end of course
      evaluations were used to evaluate student satisfaction. Game platform analytics
      and thematic analysis of narrative comments in the midterm and end of course
      surveys were used to evaluate students' level of engagement. Student learning was
      evaluated using the end of course letter grade. RESULTS: Students indicated a
      high satisfaction with the course. Student engagement was also maintained
      throughout the course. The majority of students (87%, 26/30) continued to
      complete learning quests in the game after achieving the minimum amount of points
      to earn an A. Seven students completed every learning quest available in the game
      platform. Of the 30 students enrolled in the course, 17 students earned a final
      course grade of A+ and 13 earned an A. LINKING EVIDENCE TO ACTION: Provide
      students with timely, individualized feedback to enable mastery learning. Create
      student choice and customization of learning. Integrate the use of badges (game
      mechanics) to increase engagement and motivation. Level learning activities to
      build on each other and create flow.

PMID- 27028988
TI  - The molecular mechanism of the cholesterol-lowering effect of dill and kale: The
      influence of the food matrix components.
AB  - Foods are complex matrices containing many different compounds, all of which
      contribute to the overall effect of the food itself, although they have different
      mechanisms of action. While evaluating the effect of bioactive compounds, it is
      important to consider that the use of a single compound can hide the effects of
      the other molecules that can act synergistically or antagonistically in the same
      food. The aim of the present study was to evaluate the influence of food matrix
      components by comparing two edible plants (dill and kale) with cholesterol
      lowering potential and similar contents of their most representative bioactive,
      quercetin. The molecular effects of the extracts were evaluated in HepG2 cells by
      measuring the expression of sterol-regulatory element-binding proteins (SREBPs),
      3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and low density lipoprotein
      receptor (LDLR) at the mRNA and protein level. The results reported here show
      that both extracts reduced the cellular cholesterol level with a similar trend
      and magnitude. It is conceivable that the slightly different results are due to
      the diverse composition of minor bioactive compounds, indicating that only by
      considering food as a whole is it possible to understand the complex relationship
      between food, nutrition, and health in a foodomics vision.

PMID- 27028989
TI  - Synthesis, Optical Properties, and Multiplexed Raman Bio-Imaging of Surface
      Roughness-Controlled Nanobridged Nanogap Particles.
AB  - Plasmonic nanostructures are widely studied and used because of their useful
      size, shape, composition and assembled structure-based plasmonic properties. It
      is, however, highly challenging to precisely design, reproducibly synthesize and
      reliably utilize plasmonic nanostructures with enhanced optical properties. Here,
      we devise a facile synthetic method to generate Au surface roughness-controlled
      nanobridged nanogap particles (Au-RNNPs) with ultrasmall (~1 nm) interior gap and
      tunable surface roughness in a highly controllable manner. Importantly, we found
      that particle surface roughness can be associated with and enhance the
      electromagnetic field inside the interior gap, and stronger nanogap-enhanced
      Raman scattering (NERS) signals can be generated from particles by increasing
      particle surface roughness. The finite-element method-based calculation results
      support and are matched well with the experimental results and suggest one needs
      to consider particle shape, nanogap and nanobridges simultaneously to understand
      and control the optical properties of this type of nanostructures. Finally, the
      potential of multiplexed Raman detection and imaging with RNNPs and the high
      speed, high-resolution Raman bio-imaging of Au-RNNPs inside cells with a wide
      field Raman imaging setup with liquid crystal tunable filter are demonstrated.
      Our results provide strategies and principles in designing and synthesizing
      plasmonically enhanced nanostructures and show potential for detecting and
      imaging Raman nanoprobes in a highly specific, sensitive and multiplexed manner. 

PMID- 27028990
TI  - Acute exacerbation of COPD.
AB  - The literature of acute exacerbation of chronic obstructive pulmonary disease
      (COPD) is fast expanding. This review focuses on several aspects of acute
      exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management.
      COPD poses a major health and economic burden in the Asia-Pacific region, as it
      does worldwide. Triggering factors of AECOPD include infectious (bacteria and
      viruses) and environmental (air pollution and meteorological effect) factors.
      Disruption in the dynamic balance between the 'pathogens' (viral and bacterial)
      and the normal bacterial communities that constitute the lung microbiome likely
      contributes to the risk of exacerbations. The diagnostic approach to AECOPD
      varies based on the clinical setting and severity of the exacerbation. After
      history and examination, a number of investigations may be useful, including
      oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers.
      Arterial blood gases should be considered in severe exacerbations, to
      characterize respiratory failure. Depending on the severity, the acute management
      of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and
      noninvasive ventilation. Hospitalization may be required, for severe
      exacerbations. Nonpharmacological interventions including disease-specific self
      management, pulmonary rehabilitation, early medical follow-up, home visits by
      respiratory health workers, integrated programmes and telehealth-assisted
      hospital at home have been studied during hospitalization and shortly after
      discharge in patients who have had a recent AECOPD. Pharmacological approaches to
      reducing risk of future exacerbations include long-acting bronchodilators,
      inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further
      studies are needed to assess the cost-effectiveness of these interventions in
      preventing COPD exacerbations.

PMID- 27028991
TI  - Effectiveness of honey on radiation-induced oral mucositis, time to mucositis,
      weight loss, and treatment interruptions among patients with head and neck
      malignancies: A meta-analysis and systematic review of literature.
AB  - BACKGROUND: Mucositis is a disabling effect of radiotherapy in head and neck
      cancers. There is no current standard on management of radiation-induced
      mucositis. Honey has been shown to reduce radiation-induced mucositis. METHODS: A
      systematic review and meta-analysis were undertaken to assess the ability of
      honey in reducing the severity of oral mucositis, time to mucositis, weight loss,
      and treatment interruptions. RESULTS: Eight studies were included and showed that
      honey was significantly better in lowering the risk for treatment interruptions,
      weight loss, and delaying time to mucositis, but not severity of mucositis.
      CONCLUSION: There is current evidence that honey is beneficial for patients with
      head and neck cancers by decreasing treatment interruptions, weight loss, and
      delaying the onset of oral mucositis, but not in decreasing peak mucositis score.
      In light of the results, honey is a reasonable treatment for radiation-induced
      mucositis, but more randomized clinical trials (RCTs) should be done. (c) 2016
      Wiley Periodicals, Inc. Head Neck 38: 1119-1128, 2016.

PMID- 27028992
TI  - The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell
      pathogenesis by inhibiting cellular apoptosis.
AB  - Nasopharyngeal carcinoma (NPC) is one of the most prevalent forms of highly
      invasive malignancy in Southern China and Southeast Asia. The pathogenesis of NPC
      is a multistep process driven by the acquisition of numerous genetic
      abnormalities. We investigated the potential oncogenic role of the Rho-guanine
      nucleotide exchange factor 3 gene, ARHGEF3, in NPC pathogenesis. Expression
      levels of ARHGEF3 were frequently up-regulated in NPC cell lines and tissues. In
      a large cohort of clinical NPC tissues high expression of ARHGEF3 was positively
      associated with an increased T status, distant metastasis, and a more advanced
      clinical stage (P < 0.05). Survival analysis revealed that ARHGEF3 expression was
      a significant and independent prognosis factor for NPC patients. In NPC cell
      lines, knockdown of ARHGEF3 was sufficient to inhibit cell growth, motility, and
      invasion in vitro, whereas ectopic overexpression of ARHGEF3 substantially
      enhanced NPC cells tumorigenesis and metastasis in vivo. Depletion of ARHGEF3 in
      NPC cells dramatically promoted caspase-3 induced apoptosis and an anti-apoptosis
      factor, BIRC8, was identified as a critical downstream target of the ARHGEF3. Our
      findings suggest that increased expression of ARHGEF3 plays a critical oncogenic
      role in NPC pathogenesis by preventing cell apoptosis through the up-regulation
      of BIRC8, and ARHGEF3 might be employed as a novel prognostic marker and
      effective therapeutic target for human NPC. 

PMID- 27028993
TI  - ILNCSIM: improved lncRNA functional similarity calculation model.
AB  - Increasing observations have indicated that lncRNAs play a significant role in
      various critical biological processes and the development and progression of
      various human diseases. Constructing lncRNA functional similarity networks could
      benefit the development of computational models for inferring lncRNA functions
      and identifying lncRNA-disease associations. However, little effort has been
      devoted to quantifying lncRNA functional similarity. In this study, we developed
      an Improved LNCRNA functional SIMilarity calculation model (ILNCSIM) based on the
      assumption that lncRNAs with similar biological functions tend to be involved in
      similar diseases. The main improvement comes from the combination of the concept
      of information content and the hierarchical structure of disease directed acyclic
      graphs for disease similarity calculation. ILNCSIM was combined with the
      previously proposed model of Laplacian Regularized Least Squares for lncRNA
      Disease Association to further evaluate its performance. As a result, new model
      obtained reliable performance in the leave-one-out cross validation (AUCs of
      0.9316 and 0.9074 based on MNDR and Lnc2cancer databases, respectively), and 5
      fold cross validation (AUCs of 0.9221 and 0.9033 for MNDR and Lnc2cancer
      databases), which significantly improved the prediction performance of previous
      models. It is anticipated that ILNCSIM could serve as an effective lncRNA
      function prediction model for future biomedical researches. 

PMID- 27028994
TI  - A preoperative mathematic model for computed tomographic guided microwave
      ablation treatment of hepatic dome tumors.
AB  - PURPOSE: This study sought to prospectively evaluate the feasibility and safety
      of a preoperative mathematic model for computed tomographic(CT) guided
      microwave(MW) ablation treatment of hepatic dome tumors. METHODS: This mathematic
      model was a regular cylinder quantifying appropriate puncture routes from the
      bottom up. A total of 103 patients with hepatic dome tumors were enrolled and
      randomly divided into 2 groups based on whether this model was used or not: Group
      A (using the model; n = 43) versus Group B (not using the model; n = 60). All
      tumors were treated by CT-guided MW ablation and follow-up contrast CT were
      reviewed. RESULTS: The average number of times for successful puncture, average
      ablation time, and incidence of right shoulder pain were less in Group A than
      Group B (1.4 vs. 2.5, P = 0.001; 8.8 vs. 11.1 minutes, P = 0.003; and 4.7% vs.
      20%, P = 0.039). The technical success rate was higher in Group A than Group B
      (97.7% vs. 85.0%, P = 0.032). There were no significant differences between the
      two groups in primary and secondary technique efficacy rates (97.7% vs. 88.3%, P
      = 0.081; 90.0% vs. 72.7%, P = 0.314). No major complications occurred in both
      groups. CONCLUSION: The mathematic model of regular cylinder is feasible and safe
      for CT-guided MW ablation in treating hepatic dome tumors.

PMID- 27028995
TI  - Salidroside suppresses solar ultraviolet-induced skin inflammation by targeting
      cyclooxygenase-2.
AB  - Solar ultraviolet (SUV) irradiation causes skin disorders such as inflammation,
      photoaging, and carcinogenesis. Cyclooxygenase-2 (COX-2) plays a key role in SUV
      induced skin inflammation, and targeting COX-2 may be a strategy to prevent skin
      disorders. In this study, we found that the expression of COX-2, phosphorylation
      of p38 or JNKs were increased in human solar dermatitis tissues and SUV
      irradiated human skin keratinocyte HaCaT cells and mouse epidermal JB6 Cl41
      cells. Knocking down COX-2 inhibited the production of prostaglandin E2 (PGE2),
      the phosphorylation of p38 or JNKs in SUV-irradiated cells, which indicated that
      COX-2 is not only the key enzyme for PGs synthesis, but also an upstream
      regulator of p38 or JNKs after SUV irradiation. The virtual ligand screening
      assay was used to search for natural drugs in the Chinese Medicine Database, and
      indicated that salidroside might be a COX-2 inhibitor. Molecule modeling
      indicated that salidroside can directly bind with COX-2, which was proved by in
      vitro pull-down binding assay. Ex vivo studies showed that salidroside has no
      toxicity to cells, and inhibits the production of PGE2, phosphorylation of p38 or
      JNKs, and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) caused by SUV irradiation. In vivo studies demonstrated that salidroside
      attenuates the skin inflammation induced by SUV. In brief, our data provided the
      evidences for the protective role of salidroside against SUV-induced inflammation
      by targeting COX-2, and salidroside might be a promising drug for the treatment
      of SUV-induced skin inflammation. 

PMID- 27028996
TI  - Volatile anaesthetics enhance the metastasis related cellular signalling
      including CXCR2 of ovarian cancer cells.
AB  - The majority of ovarian cancer patients relapse after surgical resection.
      Evidence is accumulating regarding the role of surgery in disseminating cancer
      cells; in particular anaesthesia may have an impact on cancer re-occurrence.
      Here, we have investigated the metastatic potential of volatile anaesthetics
      isoflurane, sevoflurane and desflurane on ovarian cancer cells. Human ovarian
      carcinoma cells (SKOV3) were exposed to isoflurane (2%), sevoflurane (3.6%) or
      desflurane (10.3%) for 2 hours. Metastatic related gene expression profiles were
      measured using the Tumour Metastasis PCR Array and qRT-PCR. Subsequently vascular
      endothelial growth factor A (VEGF-A), matrix metalloproteinase 11 (MMP11),
      transforming growth factor beta-1 (TGF-beta1) and chemokine (C-X-C motif)
      receptor 2 (CXCR2) proteins expression were determined using immunofluorescent
      staining. The migratory capacities of SK-OV3 cells were assessed with a scratch
      assay and the potential role of CXCR2 in mediating the effects of volatile
      anaesthetics on cancer cell biology were further investigated with CXCR2
      knockdown by siRNA. All three volatile anaesthetics altered expression of 70 out
      of 81 metastasic related genes with significant increases in VEGF-A, MMP-11,
      CXCR2 and TGF-beta genes and protein expression with a magnitude order of
      desflurane (greatest), sevoflurane and isoflurane. Scratch analysis revealed that
      exposure to these anesthetics increased migration, which was abolished by CXCR2
      knockdown. Volatile anaesthetics at clinically relevant concentrations have
      strong effects on cancer cell biology which in turn could enhance ovarian cancer
      metastatic potential. This work raises the urgency for further in vivo studies
      and clinical trials before any conclusions can be made in term of the alteration
      of clinical practice. 

PMID- 27028997
TI  - Alu methylation serves as a biomarker for non-invasive diagnosis of glioma.
AB  - Current techniques for diagnosing glioma are invasive and do not accurately
      predict prognosis. We developed a novel, non-invasive liquid chip assay to
      diagnose glioma and predict prognosis. Using this method, we determined the
      methylation state of the Alu element in cell-free DNA extracted from the serum of
      109 glioma patients. Controls included 56 patients with benign intracranial
      tumors and 50 healthy subjects. Matched tumor tissues were processed for 36
      patients. The cfDNA from glioma patients showed lower levels of Alu methylation
      than the controls (P<0.01). Alu methylation was also lower in high-grade than low
      grade gliomas (P<0.01), indicating that Alu methylation correlates negatively
      with disease severity. Moreover, Alu methylation correlated positively with
      survival (P<0.01). These findings suggest high-throughput liquid chip could serve
      as a non-invasive diagnostic assay for glioma. 

PMID- 27028998
TI  - Salivary HOTAIR and PVT1 as novel biomarkers for early pancreatic cancer.
AB  - Sensitive and non-invasive biomarkers for pancreatic cancer (PC) are lacking. We
      aimed to identify salivary long non-coding RNAs (lncRNAs) as biomarkers in
      diagnosis of resectable PC. Five well-documented lncRNAs: H19, HOTAIR, HOTTIP,
      MALAT1, PVT1, which are most closely associated with pancreatic cancer from
      previous studies were selected as putative lncRNA biomarkers. Their expression in
      pancreatic tissues and saliva of cancer patients and healthy controls was
      measured by quantification polymerase chain reaction (qPCR). Compared with benign
      pancreatic tumour (BPT) and normal pancreatic tissues (NPT), HOTAIR, HOTTIP and
      PVT1 were significantly up-regulated in pancreatic cancer tissues (PCT). As
      compared to BPT or healthy groups, the salivary levels of HOTAIR and PVT1 were
      significantly higher in PC group. They were significantly reduced after the
      curative pancreatectomy. Both salivary lncRNAs distinguished PC patients from
      healthy controls and BPT patients with sensitivities and specificities ranging
      from 60-97%. The expression of salivary HOTAIR and PVT1 did not differ
      significantly between healthy controls and any one of eight leading cancers
      worldwide. Collectively, our findings indicate that salivary HOTAIR and PVT1 show
      potential as novel non-invasive biomarkers for detecting PC. 

PMID- 27028999
TI  - Eukaryotic translation initiation factor 5A2 regulates the migration and invasion
      of hepatocellular carcinoma cells via pathways involving reactive oxygen species.
AB  - Eukaryotic translation initiation factor 5A2 (eIF5A2) has been identified as a
      critical gene in tumor metastasis. Research has suggested that reactive oxygen
      species (ROS) serve as signaling molecules in cancer cell proliferation and
      migration. However, the mechanisms linking eIF5A2 and ROS are not fully
      understood. Here, we investigated the effects of ROS on the eIF5A2-induced
      epithelial-mesenchymal transition (EMT) and migration in six hepatocellular
      carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell
      migration assays, wound-healing assays, and immunofluorescence analysis were
      used. The protein levels of eIF5A2 in tumor and adjacent tissue samples from 90
      HCC patients with detailed clinical, pathological, and clinical follow-up data
      were evaluated. Overexpression of eIF5A2 was found in cancerous tissues compared
      with adjacent tissues. We found that eIF5A2 overexpression in HCC was associated
      with reduced overall survival. Knockdown of eIF5A2 and intracellular reduction of
      ROS significantly suppressed the invasion and metastasis of HCC cells.
      Interestingly, N1-guanyl-1, 7-diaminoheptane (GC7) suppressed the intracellular
      ROS levels. After blocking the EMT, administration of GC7 or N-acetyl-L-cysteine
      did not reduce cell migration further. Based on the experimental data, we
      concluded that inhibition of eIF5A2 alters progression of the EMT to decrease the
      invasion and metastasis of HCC cells via ROS-related pathways. 

PMID- 27029000
TI  - XB130 deficiency enhances lipopolysaccharide-induced septic response and acute
      lung injury.
AB  - XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation
      and migration. Its physiological function in vivo is largely unknown. The
      objective of this study was to determine the role of XB130 in lipopolysaccharide
      (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally
      administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a
      significant weight loss in KO mice at Day 2 and significantly higher disease
      scores during the 7 days of observation. The levels of tumor necrosis factor
      alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in
      the serum were significantly higher in KO mice at Day 2. In KO mice there were a
      significantly higher lung injury score, higher wet/dry lung weight ratio, more
      apoptotic cells and less proliferative cells in the lung. Macrophage infiltration
      was significantly elevated in the lung of KO mice. There was significantly
      increased number of p-GSK-3beta positive cells in KO mice, which were mainly
      neutrophils and macrophages. XB130 is expressed in alveolar type I and type II
      cells in the lung. The expression in these cells was significantly reduced after
      LPS challenge. XB130 deficiency delayed the recovery from systemic septic
      responses, and the presence of XB130 in the alveolar epithelial cells may provide
      protective mechanisms by reducing cell death and promoting cell proliferation,
      and reducing pulmonary permeability. 

PMID- 27029002
TI  - Initiator and Photocatalyst-Free Visible Light Induced One-Pot Reaction:
      Concurrent RAFT Polymerization and CuAAC Click Reaction.
AB  - A new, visible light-catalyzed, one-pot and one-step reaction is successfully
      employed to design well-controlled side-chain functionalized polymers, by the
      combination of ambient temperature revisible addtion-fragmentation chain transfer
      (RAFT) polymerization and click chemistry. Polymerizations are well controlled in
      a living way under the irradiation of visible light-emitting diode (LED) light
      without photocatalyst and initiator, using the trithiocarbonate agent as
      iniferter (initiator-transfer agent-terminator) agent at ambient temperature.
      Fourier transfer infrared spectroscopy (FT-IR), NMR, and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) data
      confirm the successful one-pot reaction. Compared to the reported zero-valent
      metal-catalyzed one-pot reaction, the polymerization rate is much faster than
      that of the click reaction, and the visible light-catalyzed one-pot reaction can
      be freely and easily regulated by turning on and off the light. 

PMID- 27029001
TI  - Regulation of ErbB2 localization and function in breast cancer cells by ERM
      proteins.
AB  - The ERM protein family is implicated in processes such as signal transduction,
      protein trafficking, cell proliferation and migration. Consequently,
      dysregulation of ERM proteins has been described to correlate with carcinogenesis
      of different cancer types. However, the underlying mechanisms are poorly
      understood. Here, we demonstrate a novel functional interaction between ERM
      proteins and the ErbB2 receptor tyrosine kinase in breast cancer cells. We show
      that the ERM proteins ezrin and radixin are associated with ErbB2 receptors at
      the plasma membrane, and depletion or functional inhibition of ERM proteins
      destabilizes the interaction of ErbB2 with ErbB3, Hsp90 and Ebp50. Accompanied by
      the dissociation of this protein complex, binding of ErbB2 to the ubiquitin
      ligase c-Cbl is increased, and ErbB2 becomes dephosphorylated, ubiquitinated and
      internalized. Furthermore, signaling via Akt- and Erk-mediated pathways is
      impaired upon ERM inhibition. Finally, interference with ERM functionality leads
      to receptor degradation and reduced cellular levels of ErbB2 and ErbB3 receptors
      in breast cancer cells. 

PMID- 27029004
TI  - Case of pigmented dermatofibrosarcoma protuberans with atrophic change.

PMID- 27029003
TI  - Effects of a Closed Space Environment on Gene Expression in Hair Follicles of
      Astronauts in the International Space Station.
AB  - Adaptation to the space environment can sometimes pose physiological problems to
      International Space Station (ISS) astronauts after their return to earth.
      Therefore, it is important to develop healthcare technologies for astronauts. In
      this study, we examined the feasibility of using hair follicles, a readily
      obtained sample, to assess gene expression changes in response to spaceflight
      adaptation. In order to investigate the gene expression changes in human hair
      follicles during spaceflight, hair follicles of 10 astronauts were analyzed by
      microarray and real time qPCR analyses. We found that spaceflight alters human
      hair follicle gene expression. The degree of changes in gene expression was found
      to vary among individuals. In some astronauts, genes related to hair growth such
      as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that
      spaceflight inhibits cell proliferation in hair follicles. 

PMID- 27029005
TI  - 'Compromise' in Echolocation Calls between Different Colonies of the Intermediate
      Leaf-Nosed Bat (Hipposideros larvatus).
AB  - Each animal population has its own acoustic signature which facilitates
      identification, communication and reproduction. The sonar signals of bats can
      convey social information, such as species identity and contextual information.
      The goal of this study was to determine whether bats adjust their echolocation
      call structures to mutually recognize and communicate when they encounter the
      bats from different colonies. We used the intermediate leaf-nosed bats
      (Hipposideros larvatus) as a case study to investigate the variations of
      echolocation calls when bats from one colony were introduced singly into the home
      cage of a new colony or two bats from different colonies were cohabitated
      together for one month. Our experiments showed that the single bat individual
      altered its peak frequency of echolocation calls to approach the call of new
      colony members and two bats from different colonies adjusted their call
      frequencies toward each other to a similar frequency after being chronically
      cohabitated. These results indicate that the 'compromise' in echolocation calls
      might be used to ensure effective mutual communication among bats. 

PMID- 27029006
TI  - A Personalized Approach to Biological Therapy Using Prediction of Clinical
      Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients.
AB  - OBJECTIVES: Measurement of MRP8/14 serum levels has shown potential in predicting
      clinical response to different biological agents in rheumatoid arthritis (RA). We
      aimed to develop a treatment algorithm based on a prediction score using MRP8/14
      measurements and clinical parameters predictive for response to different
      biological agents. METHODS: Baseline serum levels of MRP8/14 were measured in 170
      patients starting treatment with infliximab, adalimumab or rituximab. We used
      logistic regression analysis to develop a predictive score for clinical response
      at 16 weeks. MRP8/14 levels along with clinical variables at baseline were
      investigated. We also investigated how the predictive effect of MRP8/14 was
      modified by drug type. A treatment algorithm was developed based on categorizing
      the expected response per drug type as high, intermediate or low for each patient
      and optimal treatment was defined. Finally, we present the utility of using this
      treatment algorithm in clinical practice. RESULTS: The probability of response
      increased with higher baseline MRP8/14 complex levels (OR = 1.39), differentially
      between the TNF-blockers and rituximab (OR of interaction term = 0.78), and also
      increased with higher DAS28 at baseline (OR = 1.28). Rheumatoid factor
      positivity, functional disability (a higher HAQ), and previous use of a TNF
      inhibitor decreased the probability of response. Based on the treatment algorithm
      80 patients would have been recommended for anti-TNF treatment, 8 for rituximab,
      13 for another biological treatment (other than TNFi or rituximab) and for 69 no
      recommendation was made. The predicted response rates matched the observed
      response in the cohort well. On group level the predicted response based on the
      algorithm resulted in a modest 10% higher response rate in our cohort with much
      higher differences in response probability in individual patients treated
      contrary to treatment recommendation. CONCLUSIONS: Prediction of response using
      MRP8/14 levels along with clinical predictors has potential in personalizing
      treatment for RA patients starting biological anti-rheumatic treatment, and might
      increase cost-effectiveness.

PMID- 27029007
TI  - A comparative study using WHO and binary oral epithelial dysplasia grading
      systems in actinic cheilitis.
AB  - OBJECTIVE: To evaluate comparatively the influence of histopathological features
      on epithelial dysplasia (ED) and the effectiveness in usage of WHO and binary
      grading systems in actinic cheilitis (AC). MATERIAL AND METHODS: Cytological and
      architectural alterations established by WHO for ED were evaluated in 107 cases
      of AC. Epithelial dysplasia was graded using WHO and binary systems. The
      comparisons were performed using kappa, chi-square, and phi coefficient tests (P
      < 0.05). RESULTS: Most cases were classified as mild ED (44.5%) in the WHO system
      and as low risk for malignant transformation (64.5%) in the binary system. There
      was a positive correlation between WHO and binary systems (k = 0.33; P < 0.0002).
      Loss of basal cell polarity (P < 0.001) was associated with severity of ED grade
      in the WHO system. Anisonucleosis (P < 0.0001), nuclear pleomorphism (P <
      0.0001), anisocytosis (P = 0.03), cell pleomorphism (P = 0.002) increased
      nuclear/cytoplasm ratio (P < 0.0001), increased nuclear size (P < 0.0001),
      increased number of mitotic figures (P = 0.0006), and dyskeratosis (P = 0.008)
      were associated with severity of ED grade in the binary system. CONCLUSIONS: It
      seems that usage of binary ED grading system in AC may be more precise because
      there is correlation between many of cytological and some of architectural
      microscopic alterations with increased grade of ED.

PMID- 27029008
TI  - [Not Available].

PMID- 27029010
TI  - The complexities of benchmarking surgical complications in gynaecological
      oncology.

PMID- 27029009
TI  - R-Ras Inhibits VEGF-Induced p38MAPK Activation and HSP27 Phosphorylation in
      Endothelial Cells.
AB  - R-Ras is a Ras family small GTPase that is highly expressed in mature functional
      blood vessels in normal tissues. It inhibits pathological angiogenesis and
      promotes vessel maturation and stabilization. Previous studies suggest that R-Ras
      affects cellular signaling in endothelial cells, pericytes and smooth-muscle
      cells to regulate vessel formation and remodeling in adult tissues. R-Ras
      suppresses VEGF-induced endothelial permeability and vessel sprouting while
      promoting normalization of pathologically developing vessels in mice. It
      attenuates VEGF receptor-2 (VEGFR2) activation by inhibiting internalization of
      the receptor upon VEGF ligand binding, leading to significant reduction of VEGFR2
      autophosphorylation. Here, we show that R-Ras strongly suppresses the VEGF
      dependent activation of stress-activated protein kinase-2/p38 mitogen-activated
      protein kinase (SAPK2/p38MAPK) and the phosphorylation of downstream heat-shock
      protein 27 (HSP27), a regulator of actin cytoskeleton organization, in
      endothelial cells. The suppression of p38MAPK activation and HSP27
      phosphorylation by R-Ras concurred with altered actin cytoskeleton architecture,
      reduced membrane protrusion and inhibition of endothelial cell migration toward
      VEGF. Silencing of endogenous R-Ras by RNA interference increased membrane
      protrusion and cell migration stimulated by VEGF, and these effects were offset
      by p38MAPK inhibitor SB203580. These results suggest that R-Ras regulates
      angiogenic activities of endothelial cells in part via inhibition of the p38MAPK
      HSP27 axis of VEGF signaling. 

PMID- 27029011
TI  - Scanning Electron Microscopic Examination of the Extracellular Matrix in the
      Decellularized Mouse and Human Cochlea.
AB  - Decellularized tissues have been used to investigate the extracellular matrix
      (ECM) in a number of different tissues and species. Santi and Johnson JARO 14:3
      15 (2013) first described the decellularized inner ear in the mouse, rat, and
      human using scanning thin-sheet laser imaging microscopy (sTSLIM). The purpose of
      the present investigation is to examine decellularized cochleas in the mouse and
      human at higher resolution using scanning electron microscopy (SEM). Fresh
      cochleas were harvested and decellularized using detergent extraction methods.
      Following decellularization, the ECM of the bone, basilar membrane, spiral
      limbus, and ligament remained, and all of the cells were removed from the
      cochlea. A number of similarities and differences in the ECM of the mouse and
      human were observed. A novel, spirally directed structure was present on the
      basilar membrane and is located at the border between Hensen and Boettcher cells.
      These septa-like structures formed a single row in the mouse and multiple rows in
      the human. The basal lamina of the stria vascularis capillaries was present and
      appeared thicker in the human compared with the mouse. In the mouse, numerous
      openings beneath the spiral prominence that previously housed the root processes
      of the external sulcus cells were observed but in the human there was only a
      single row of openings. These and other anatomical differences in the ECM between
      the mouse and human may reflect functional differences and/or be due to aging;
      however, decellularized cochleas provide a new way to examine the cochlear ECM
      and reveal new observations.

PMID- 27029013
TI  - Alcohol consumption and risk of periodontitis: a meta-analysis.
AB  - AIM: A meta-analysis was conducted to quantitatively summarize the evidence from
      observational studies on alcohol consumption and risk of periodontitis. MATERIAL
      AND METHODS: A comprehensive literature search was performed in PubMed, Web of
      Science and Embase databases to identify eligible studies published in English.
      Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated
      by random-effects models. Restricted cubic splines were used to assess the dose
      response relationship. RESULTS: Eighteen studies were included in our meta
      analysis. The pooled RR of periodontitis for the highest with the lowest alcohol
      consumption was 1.59 (95% CI: 1.37-1.85). Significant associations were also
      found in stratified analysis by gender [males: (1.25, 95% CI: 1.11-1.41), females
      (2.15, 95% CI: 1.36-3.41)] and study design [cohort studies: 1.28 (1.04-1.57) and
      cross-sectional studies: 1.66 (1.39-1.99)]. A linear dose-response relationship
      was found between alcohol consumption and periodontitis risk, and the risk of
      periodontitis increased by 0.4% [95% CI (1.002-1.007) (p = 0.002)] for each 1
      g/day increment in alcohol consumption. CONCLUSION: This meta-analysis suggested
      that alcohol consumption was associated with an increased risk of periodontitis.

PMID- 27029012
TI  - The Klebsiella pneumoniae YfgL (BamB) lipoprotein contributes to outer membrane
      protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, and in vivo
      virulence.
AB  - Klebsiella pneumoniae is an opportunistic pathogen that causes several kinds of
      infections, including pneumonia, bacteremia, urinary tract infection and
      community-acquired pyogenic liver abscess (PLA). Adhesion is the critical first
      step in the infection process. Our previous work demonstrated that the
      transcellular translocation is exploited by K. pneumoniae strains to migrate from
      the gut flora into other tissues, resulting in systemic infections. However, the
      initial stages of K. pneumoniae infection remain unclear. In this study, we
      demonstrated that a K. pneumoniae strain deleted for yfgL (bamB) exhibited
      reduced adherence to and invasion of host cells; changed biogenesis of major beta
      barrel outer membrane proteins; decreased transcriptional expression of type-1
      fimbriae; and increased susceptibility to vancomycin and erythromycin. The yfgL
      deletion mutant also had reduced ability to against neutrophil phagocytosis;
      exhibited decreased induction of host IL-6 production; and was profoundly
      attenuated for virulence in a K. pneumoniae model of bacteremia. Thus, the K.
      pneumoniae YfgL lipoprotein mediates in outer membrane proteins biogenesis and is
      crucial for anti-phagocytosis and survival in vivo. These data provide a new
      insight for K. pneumoniae attachment and such knowledge could facilitate
      preventive therapies or alternative therapies against K. pneumoniae.

PMID- 27029014
TI  - Elevated p16ink4a Expression in Human Labial Salivary Glands as a Potential
      Correlate of Cognitive Aging in Late Midlife.
AB  - BACKGROUND: The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase
      inhibitor, p16ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a)
      locus on chromosome 9q21. Up-regulation of p16ink4a has been linked to cellular
      senescence, and findings from studies on different mammalian tissues suggest that
      p16ink4a may be a biomarker of organismal versus chronological age. OBJECTIVE:
      The aim of this study was to examine the immunolocalization pattern of p16ink4a
      in human labial salivary gland (LSG) tissue, and to analyze whether its
      expression level in LSGs is a peripheral correlate of cognitive decline in late
      midlife. METHODS: The present study was a part of a study of causes and
      predictors of cognitive decline in middle-aged men in a Danish birth cohort. It
      is based on data from 181 male participants from the Danish Metropolit birth
      cohort, born in 1953, who were examined for age-associated alterations in
      cognition, dental health, and morphological and autonomic innervation
      characteristics of the LSGs. The participants were allocated to two groups based
      on the relative change in cognitive performance from young adulthood to late
      midlife. LSG biopsies were analyzed by qRT-PCR for the expression level of
      p16ink4a. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded
      sections of LSGs. RESULTS: p16ink4a immunoreactivity was observed in LSG ductal,
      myoepithelial, and stromal cells, but not in acinar cells. The mean relative
      expression of p16ink4a in LSGs was higher in the group of participants with
      decline in cognitive performance. A logistic regression analysis revealed that
      the relative p16 expression was predictive of the participant's group assignment.
      A negative correlation was found between relative p16ink4a expression and the
      participant's standardized regression residuals from early adulthood to late
      midlife cognitive performance scores. CONCLUSIONS: p16ink4a expression in human
      LSGs may constitute a potential peripheral correlate of cognitive decline. Human
      labial salivary glands seem suitable for studies on organismal as opposed to
      chronological age.

PMID- 27029015
TI  - Factors shaping e-feedback utilization following electronic Objective Structured
      Clinical Examinations.
AB  - The development of student-practitioners' practical clinical skills is essential
      in health professional education. Objective Structured Clinical Examinations are
      central to the assessment of students performing clinical procedures on simulated
      patients (actors). While feedback is considered core to learning providing
      timely, individualised student OSCE feedback is difficult. This study explored
      the perceptions of students about the multiple factors which shape the utility of
      e-feedback following an electronic Objective Structured Clinical Examinations,
      which utilized iPad and specialised software. The e-feedback was trialled in four
      courses within occupational therapy and physiotherapy pre-professional programs
      with a cohort of 204 students. Evaluation of student perceptions about feedback
      was collected using two surveys and eight focus groups. This data showed three
      factors shaped perceptions of the utility of e- Objective Structured Clinical
      Examinations feedback: 1) timely accessibility within one day of the assessment,
      2) feedback demonstrating examiners' academic literacy and 3) feedback orientated
      to ways of improving future performance of clinical skills. The study found
      training in the provision of feedback using IPads and software is needed for
      examiners to ensure e-feedback meets students' needs for specific, future
      oriented e-feedback and institutional requirements for justification of grades. 

PMID- 27029016
TI  - Liver transplant using octogenarian donors.

PMID- 27029017
TI  - Evolution of Imaging in Breast Cancer.
AB  - The following topics are discussed in this article. A historical review of the
      evolution of breast cancer imaging from thermography through digital breast
      tomosynthesis, molecular breast imaging, and advanced breast magnetic resonance
      imaging. Discussion of multiple clinical trials, their strengths, and weaknesses.
      Historical perspective on the Mammography Quality Standards Act and its
      relationship with development and implementation of the Breast Imaging-Reporting
      and Data System (BI-RADS). 

PMID- 27029018
TI  - The changing circumstance of atrial fibrillation - progress towards precision
      medicine.
AB  - The prevalence of atrial fibrillation (AF) in the general population is between
      1% and 2% in the developed world and is higher in men than in women. The
      arrhythmia occurs much more commonly in the elderly, and the estimated lifetime
      risk of developing AF is one in four for men and women aged 40 years and above.
      Projected data from multiple population-based studies in the USA and Europe
      predict a two- to threefold increase in the number of AF patients by 2060. The
      high lifetime risk of AF and increased longevity underscore the important public
      health burden posed by this arrhythmia worldwide. AF has multiple aetiologies and
      a broad variety of presentations. The primary pathologies underlying or promoting
      the occurrence of AF vary more than for any other cardiac arrhythmia, ranging
      from autonomic imbalance to organic heart disease and metabolic disorders, such
      as diabetes mellitus, metabolic syndrome, hyperthyroidism and kidney disease, and
      lifestyle factors such as smoking, alcohol consumption and participation in
      endurance sports. Biomarkers are increasingly being investigated and, together
      with clinical and genetic factors, will eventually lead to a clinically valuable
      detailed classification of AF which will also incorporate pathophysiological
      determinants and mechanisms of the arrhythmia. In turn, this will allow the
      development and application of precision medicine to this troublesome arrhythmia.

PMID- 27029020
TI  - Recombinant Cyanobacteria for the Asymmetric Reduction of C=C Bonds Fueled by the
      Biocatalytic Oxidation of Water.
AB  - A recombinant enoate reductase was expressed in cyanobacteria and used for the
      light-catalyzed, enantioselective reduction of C=C bonds. The coupling of
      oxidoreductases to natural photosynthesis allows asymmetric syntheses fueled by
      the oxidation of water. Bypassing the addition of sacrificial cosubstrates as
      electron donors significantly improves the atom efficiency and avoids the
      formation of undesired side products. Crucial factors for product formation are
      the availability of NADPH and the amount of active enzyme in the cells. The
      efficiency of the reaction is comparable to typical whole-cell biotransformations
      in E. coli. Under optimized conditions, a solution of 100 mg prochiral 2
      methylmaleimide was reduced to optically pure 2-methylsuccinimide (99 % ee, 80 %
      yield of isolated product). High product yields and excellent optical purities
      demonstrate the synthetic usefulness of light-catalyzed whole-cell
      biotransformations using recombinant cyanobacteria.

PMID- 27029019
TI  - Human Cells Require Non-stop Ribosome Rescue Activity in Mitochondria.
AB  - Bacteria use trans-translation and the alternative rescue factors ArfA (P36675)
      and ArfB (Q9A8Y3) to hydrolyze peptidyl-tRNA on ribosomes that stall near the 3'
      end of an mRNA during protein synthesis. The eukaryotic protein ICT1 (Q14197) is
      homologous to ArfB. In vitro ribosome rescue assays of human ICT1 and Caulobacter
      crescentus ArfB showed that these proteins have the same activity and substrate
      specificity. Both ArfB and ICT1 hydrolyze peptidyl-tRNA on nonstop ribosomes or
      ribosomes stalled with <=6 nucleotides extending past the A site, but are unable
      to hydrolyze peptidyl-tRNA when the mRNA extends >=14 nucleotides past the A
      site. ICT1 provided sufficient ribosome rescue activity to support viability in
      C. crescentus cells that lacked both trans-translation and ArfB. Likewise,
      expression of ArfB protected human cells from death when ICT1 was silenced with
      siRNA. These data indicate that ArfB and ICT1 are functionally interchangeable,
      and demonstrate that ICT1 is a ribosome rescue factor. Because ICT1 is essential
      in human cells, these results suggest that ribosome rescue activity in
      mitochondria is required in humans. 

PMID- 27029021
TI  - Methamphetamine-induced enhancement of hippocampal long-term potentiation is
      modulated by NMDA and GABA receptors in the shell-accumbens.
AB  - Addictive drugs modulate synaptic transmission in the meso-corticolimbic system
      by hijacking normal adaptive forms of experience-dependent synaptic plasticity.
      Psychostimulants such as METH have been shown to affect hippocampal synaptic
      plasticity, albeit with a less understood synaptic mechanism. METH is one of the
      most addictive drugs that elicit long-term alterations in the synaptic plasticity
      in brain areas involved in reinforcement learning and reward processing. Dopamine
      transporter (DAT) is one of the main targets of METH. As a substrate for DAT,
      METH decreases dopamine uptake and increases dopamine efflux via the transporter
      in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due
      to cross talk between NAc and hippocampus, stimulation of NAc has been shown to
      alter hippocampal plasticity. In this study, we tested the hypothesis that
      manipulation of glutamatergic and GABA-ergic systems in the shell-NAc modulates
      METH-induced enhancement of long term potentiation (LTP) in the hippocampus. Rats
      treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared
      to saline-treated animals. Intra-NAc infusion of muscimol (GABA receptor agonist)
      decreased METH-induced enhancement of dentate gyrus (DG)-LTP, while infusion of
      AP5 (NMDA receptor antagonist) prevented METH-induced enhancement of LTP. These
      data support the interpretation that reducing NAc activity can ameliorate METH
      induced hippocampal LTP through a hippocampus-NAc-VTA circuit loop. Synapse
      70:325-335, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27029022
TI  - Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein may
      predict liver fibrosis and progression to hepatocellular carcinoma in patients
      with chronic hepatitis B virus infection.
AB  - AIM: Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding
      protein (WFA+ -M2BP) is a reliable, non-invasive marker of liver fibrosis. This
      study assessed the ability of WFA+ -M2BP to diagnose liver fibrosis in patients
      with chronic hepatitis B virus (HBV) infection and evaluated WFA+ -M2BP as a
      predictor of hepatocellular carcinoma (HCC) development. METHODS: Serum WFA+ 
      M2BP values were retrospectively evaluated in 112 treatment-naive patients with
      HBV-related chronic hepatitis and cirrhosis who had undergone liver biopsy at our
      hospital. RESULTS: Serum WFA+ -M2BP levels were significantly related with liver
      fibrosis (r = 0.3725, P = 0.001). Fibrosis stage F2, F3, and F4 had a cut-off
      index of 0.94, 1.26, and 1.26, respectively. For diagnosing F >= 2 fibrosis, the
      area under the receiver-operating characteristic curve for WFA+ -M2BP was 0.713
      and comparable with those of other non-invasive fibrosis markers, such as
      hyaluronic acid, type IV collagen 7S, aspartate aminotransferase-to-platelet
      ratio index, fibrosis-4 index, serum albumin, and platelet count. Multivariate
      analysis identified male, WFA+ -M2BP >=0.71, alanine aminotransferase >=80 IU/L,
      and platelet count <14.5 * 109 /L as independent risk factors for the development
      of HCC in patients with HBV infection. CONCLUSIONS: Serum WFA+ -M2BP values
      appear to be useful for assessing liver fibrosis stage and are independently
      associated with HCC development in patients with chronic HBV infection.

PMID- 27029024
TI  - Non-invasive assessment of corneal and conjunctival deterioration in soft contact
      lens users using anterior segment optical coherence tomography.
AB  - BACKGROUND: The aim was to evaluate the corneal and bulbar conjunctival
      thicknesses of soft contact lens (SCL) wearers using anterior segment optical
      coherence tomography (AS-OCT). METHODS: The epithelial and overall thicknesses of
      both the central cornea and the infero-temporal bulbar conjunctiva of SCL wearers
      (30 subjects) were obtained by Cirrus HD-OCT and compared with those of
      refraction-matched controls (30 subjects) and patients with emmetropia (30
      subjects). RESULTS: The mean corneal epithelial thicknesses in SCL wearing,
      spectacle-wearing and emmetropic groups were 48.97 +/- 5.45, 52.18 +/- 4.84 and
      53.18 +/- 5.05 um, respectively. The corneal epithelium of members of the SCL
      group was significantly thinner than in both the spectacles and emmetropic groups
      (p = 0.044 and 0.006, respectively), whereas the central corneal thickness did
      not differ between groups (p = 0.210). The mean conjunctival epithelial
      thicknesses in SCL, spectacles and emmetropic groups were 41.50 +/- 7.75, 54.33
      +/- 8.39 and 49.10 +/- 7.11 um, respectively. Conjunctival epithelium in the SCL
      group was significantly thinner than in both spectacle-wearing and emmetropic
      groups (p < 0.001 and p = 0.001, respectively). The conjunctiva was significantly
      thinner in the SCL group compared to the spectacles group (p = 0.001) but not the
      emmetropic group. CONCLUSIONS: Contact lens wear is related to thinning of both
      corneal and conjunctival layers. AS-OCT is a non-invasive and clinically
      applicable technique for assessing the involvement of the cornea and conjunctiva
      in contact lens wearers.

PMID- 27029023
TI  - Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in
      Oropharyngeal Candidiasis.
AB  - Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because
      of its inability to form hyphae, are understudied. Since both Candida albicans
      and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we
      examined their co-adhesion in vitro and observed adhesion of C. glabrata only to
      C. albicans hyphae microscopically. Mice were infected sublingually with C.
      albicans or C. glabrata individually, or with both species concurrently, to study
      their ability to cause OPC. Infection with C. glabrata alone resulted in
      negligible infection of tongues; however, colonization by C. glabrata was
      increased by co-infection or a pre-established infection with C. albicans.
      Furthermore, C. glabrata required C. albicans for colonization of tongues, since
      decreasing C. albicans burden with fluconazole also reduced C. glabrata. C.
      albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion
      of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes
      EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to
      C. albicans hyphae and remarkably, their expression was induced by incubation
      with germinated C. albicans. Thus, we found a near essential requirement for the
      presence of C. albicans for both initial colonization and establishment of OPC
      infection by C. glabrata. 

PMID- 27029025
TI  - Bioactive factors in milk across lactation: Maternal effects and influence on
      infant growth in rhesus macaques (Macaca mulatta).
AB  - Among mammals, numerous bioactive factors in milk vary across mothers and
      influence offspring outcomes. This emerging area of research has primarily
      investigated such dynamics within rodent biomedical models, domesticated dairy
      breeds, and among humans in clinical contexts. Less understood are signaling
      factors in the milk of non-human primates. Here, we report on multiple bioactive
      components in rhesus macaque (Macaca mulatta) milk and their associations with
      maternal and infant characteristics. Milk samples were collected from 59 macaques
      at multiple time points across lactation in conjunction with maternal and infant
      morphometrics and life-history animal records. Milk was assayed for adiponectin
      (APN), epidermal growth factor (EGF) and its receptor (EGF-R), and transforming
      growth factor beta 2 (TGF-beta2 ). Regression models were constructed to assess
      the contributions of maternal factors on variation in milk bioactives, and on the
      relationship of this variation to infant body mass and growth. Maternal body
      mass, parity, social rank, and infant sex were all predictive of concentrations
      of milk bioactives. Primiparous mothers produced milk with higher adiponectin,
      but lower EGF, than multiparous mothers. Heavier mothers produced milk with lower
      EGF and EGF-R, but higher TGF-beta2 . Mothers of daughters produced milk with
      higher TGF-beta2 . Mid-ranking mothers produced milk with higher mean EGF and
      adiponectin concentrations than low-ranking mothers. Milk EGF and EGF-R were
      positively associated with infant body mass and growth rate. Importantly, these
      signaling bioactives (APN, EGF, EGF-R, and TGF-beta2 ) were significantly
      correlated with nutritional values of milk. The effects of milk signals remained
      after controlling for the available energy in milk revealing the added
      physiological role of non-nutritive milk bioactives in the developing infant.
      Integrating analyses of energetic and other bioactive components of milk yields
      an important perspective for interpreting the magnitude, sources, and
      consequences of inter-individual variation in milk synthesis. Am. J. Primatol.
      78:838-850, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27029026
TI  - Diffusion tensor imaging of the substantia nigra in Parkinson's disease
      revisited.
AB  - OBJECTIVE: To analyze diffusion tensor imaging (DTI) data in the substantia nigra
      (SN) using a more consistent region of interest (ROI) defined by neuromelanin
      sensitive MRI in order to assess Parkinson's disease (PD) related changes in
      diffusion characteristics in the SN. METHODS: T1 -weighted and DTI data were
      obtained in a cohort of 37 subjects (17 control subjects and 20 subjects with
      PD). The subjects in the PD group were clinically diagnosed PD patients with an
      average Unified Parkinsonian Disease Rating Scale (UPDRS)-III score of 23.2 +/-
      9.3. DTI data were analyzed using SN ROIs defined by neuromelanin-sensitive MRI
      and, for comparison, with ROIs defined on T2 -weighted images (b = 0 images).
      RESULTS: Compared with control subjects, significantly lower fractional
      anisotropy was observed in PD in the neuromelanin SN ROI but not in the ROI
      derived from the T2 -weighted image. This decrease was largest in the rostral and
      lateral portions of the neuromelanin volume, which were found to have more
      hypointensity in the T2 -weighted image and, presumably, higher iron content in
      the PD group. In addition, a larger decrease in fractional anisotropy was seen in
      the SN region of interest on the side contralateral to the side exhibiting more
      severe symptoms. These results indicate that the use of neuromelanin sensitive
      MRI to define the ROI in the SN for analyzing DTI data leads to more significant
      results, enhancing the robustness of DTI study and DTI based biomarkers of PD.
      Hum Brain Mapp 37:2547-2556, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27029028
TI  - Toward Understanding Whether Interactive Surface Area Could Direct Ordered
      Macroscopic Supramolecular Self-Assembly.
AB  - The mismatching phenomena are ubiquitous in complex and advanced self-assembly,
      such as hierarchical assembly, macroscopic supramolecular assembly, and so on.
      Recently, for macroscopic supramolecular assembly, the strategy of maximizing the
      interactive surface area was used and supposed to handle this problem; however,
      now there is little understanding of whether interactive surface area is the
      dominant factor to guide the assembly patterns. Herein by taking millimeter
      cylinder building blocks with different diameter/height (d/h) ratios as model
      systems, we have investigated the interactive-surface-area-dependent assembling
      behaviors in macroscopic supramolecular assembly. The results showed that the
      increasing d/h ratio of cylinders contributed to selectivity of face-to-face
      assembled pattern over face-to-side or side-to-side geometries, thus having
      improved the ordering degree of the assembled structures; however, the
      mismatching phenomena could not be totally avoided due to high colliding chances
      in kinetics and the thermally favorable stability of these structures. We further
      confirmed the above hypothesis by in situ measurements of interactive forces of
      building blocks with different assembled patterns. This work of macroscopic
      supramolecular assembly provides an in situ visible platform, which is
      significant to clarify the influences of interactive surface area on the assembly
      behaviors. 

PMID- 27029027
TI  - Respiratory modulation of human autonomic function: long-term neuroplasticity in
      space.
AB  - KEY POINTS: We studied healthy astronauts before, during and after the Neurolab
      Space Shuttle mission with controlled breathing and apnoea, to identify autonomic
      changes that might contribute to postflight orthostatic intolerance. Measurements
      included the electrocardiogram, finger photoplethysmographic arterial pressure,
      respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle
      sympathetic activity. Arterial pressure fell and then rose in space, and drifted
      back to preflight levels after return to Earth. Vagal metrics changed in opposite
      directions: vagal baroreflex gain and two indices of vagal fluctuations rose and
      then fell in space, and descended to preflight levels upon return to Earth.
      Sympathetic burst frequencies (but not areas) were greater than preflight in
      space and on landing day, and astronauts' abilities to modulate both burst areas
      and frequencies during apnoea were sharply diminished. Spaceflight triggers long
      term neuroplastic changes reflected by reciptocal sympathetic and vagal
      motoneurone responsiveness to breathing changes. ABSTRACT: We studied six healthy
      astronauts five times, on Earth, in space on the first and 12th or 13th day of
      the 16 day Neurolab Space Shuttle mission, on landing day, and 5-6 days later.
      Astronauts followed a fixed protocol comprising controlled and random frequency
      breathing and apnoea, conceived to perturb their autonomic function and identify
      changes, if any, provoked by microgravity exposure. We recorded the
      electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon
      dioxide concentrations and volumes, and peroneal nerve muscle sympathetic
      activity on Earth (in the supine position) and in space. (Sympathetic nerve
      recordings were made during three sessions: preflight, late mission and landing
      day.) Arterial pressure changed systematically from preflight levels: pressure
      fell during early microgravity exposure, rose as microgravity exposure continued,
      and drifted back to preflight levels after return to Earth. Vagal metrics changed
      in opposite directions: vagal baroreflex gain and two indices of vagal
      fluctuations (root mean square of successive normal R-R intervals; and proportion
      of successive normal R-R intervals greater than 50 ms, divided by the total
      number of normal R-R intervals) rose significantly during early microgravity
      exposure, fell as microgravity exposure continued, and descended to preflight
      levels upon return to Earth. Sympathetic mechanisms also changed. Burst
      frequencies (but not areas) during fixed frequency breathing were greater than
      preflight in space and on landing day, but their control during apnoea was
      sharply altered: astronauts increased their burst frequencies from already high
      levels, but they could not modulate either burst areas or frequencies
      appropriately. Space travel provokes long-lasting sympathetic and vagal
      neuroplastic changes in healthy humans.

PMID- 27029029
TI  - Molecular imaging of movement disorders.
AB  - Positron emission tomography measures the activity of radioactively labeled
      compounds which distribute and accumulate in central nervous system regions in
      proportion to their metabolic rate or blood flow. Specific circuits such as the
      dopaminergic nigrostriatal projection can be studied with ligands that bind to
      the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and
      D2). Single photon emission computerized tomography (SPECT) measures the activity
      of similar tracers labeled with heavy radioactive species such as technetium and
      iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal
      GABAergic function in premotor cortices, dentate nuclei and ventral thalami,
      without significant abnormalities in dopaminergic transmission. In Huntington's
      disease, there is hypometabolism in the striatum, frontal and temporal cortices.
      Disease progression is accompanied by reduction in striatal D1 and D2 binding
      that correlates with trinucleotide repeat length, disease duration and severity.
      In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor
      areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen
      during dystonic movements, which can be modulated by globus pallidus deep brain
      stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor,
      premotor and somatosensory cortices. In Tourette's syndrome, there is
      hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism
      in the striatum, thalamus and limbic regions at rest. During tics, multiple areas
      related to cognitive, sensory and motor functions become hypermetabolic. Also,
      there is abnormal serotoninergic transmission in prefrontal cortices and
      bilateral thalami, as well as hyperactivity in the striatal dopaminergic system
      which can be modulated with thalamic DBS. In Parkinson's disease (PD), there is
      asymmetric progressive decline in striatal dopaminergic tracer accumulation,
      which follows a caudal-to-rostral direction. Uptake declines prior to symptom
      presentation and progresses from contralateral to the most symptomatic side to
      bilateral, correlating with symptom severity. In progressive supranuclear palsy
      (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and
      diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be
      present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse
      reduction of striatal activity, contralateral to the most symptomatic side.
      Additionally, there is hypometabolism in contralateral parieto-occipital and
      frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate,
      thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and
      contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is
      decreased in PD. The capacity of molecular imaging to provide in vivo time
      courses of gene expression, protein synthesis, receptor and transporter binding,
      could facilitate the development and evaluation of novel medical, surgical and
      genetic therapies in movement disorders. 

PMID- 27029030
TI  - Methylation-regulated miR-124-1 suppresses tumorigenesis in hepatocellular
      carcinoma by targeting CASC3.
AB  - This study was to investigate the roles and mechanisms of miR-124-1 in
      hepatocellular carcinoma (HCC). We analyzed the expression of miR-124-1 in human
      HCC tissues and cell lines. Luciferase reporter assays were used to analyze the
      target of miR-124-1. Human HCC cell lines were transduced with lentiviruses
      expressing miR-124-1, and proliferation and colony formation were analyzed. The
      growth of human HCC cells overexpressing miR-124-1 was assessed in nude mice. The
      expression of p38-MAPK, JNK, ERK and related signaling molecules was detected by
      western blotting and immunohistochemistry. Our results showed that miR-124-1
      levels were reduced in HCC tissues and cell lines compared with those in adjacent
      non-cancer tissues and normal liver cell lines respectively. Downregulation of
      miR-124-1 in HCC cell lines were attributed to hypermethylation of its promoter
      region. Overexpression of miR-124-1 inhibited HCC cell proliferation in vitro,
      whereas miR-124-1 was correlated with clinicopathological parameters of HCC
      patients. HCC cell-mediated overexpression of miR-124-1 in nude mice suppressed
      tumor growth. Cancer susceptibility candidate 3 (CASC3) was identified as a
      direct target of miR-124-1 by computational analysis and experimental assays. MiR
      124-1-mediated downregulation of CASC3 resulted in the inactivation of p38-MAPK,
      JNK and ERK. Our findings provide potential new targets for the prevention or
      treatment of HCC. 

PMID- 27029031
TI  - Dual inhibition of ATR and ATM potentiates the activity of trabectedin and
      lurbinectedin by perturbing the DNA damage response and homologous recombination
      repair.
AB  - Trabectedin (Yondelis(r), ecteinascidin-743, ET-743) is a marine-derived natural
      product approved for treatment of advanced soft tissue sarcoma and relapsed
      platinum-sensitive ovarian cancer. Lurbinectedin is a novel anticancer agent
      structurally related to trabectedin. Both ecteinascidins generate DNA double
      strand breaks that are processed through homologous recombination repair (HRR),
      thereby rendering HRR-deficient cells particularly sensitive. We here
      characterize the DNA damage response (DDR) to trabectedin and lurbinectedin in
      HeLa cells. Our results show that both compounds activate the ATM/Chk2 (ataxia
      telangiectasia mutated/checkpoint kinase 2) and ATR/Chk1 (ATM and RAD3
      related/checkpoint kinase 1) pathways. Interestingly, pharmacological inhibition
      of Chk1/2, ATR or ATM is not accompanied by any significant improvement of the
      cytotoxic activity of the ecteinascidins while dual inhibition of ATM and ATR
      strongly potentiates it. Accordingly, concomitant inhibition of both ATR and ATM
      is an absolute requirement to efficiently block the formation of gamma-H2AX,
      MDC1, BRCA1 and Rad51 foci following exposure to the ecteinascidins. These
      results are not restricted to HeLa cells, but are shared by cisplatin-sensitive
      and -resistant ovarian carcinoma cells. Together, our data identify ATR and ATM
      as central coordinators of the DDR to ecteinascidins and provide a mechanistic
      rationale for combining these compounds with ATR and ATM inhibitors. 

PMID- 27029033
TI  - Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and
      cancers: a multicenter study in China.
AB  - PURPOSE: To analyze the clinical performance of p16/Ki-67 dual-stained cytology
      identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese
      women. METHODS: 1079 women attending ongoing cervical cancer screening and 211
      "enriched" women aged >=30yrs with biopsy-confirmed CIN2+ from five Chinese
      hospitals were enrolled during year 2014-2015. Cervical specimens were collected
      for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology
      (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women
      with any abnormal result. RESULTS: p16/Ki-67 positivity increased with histologic
      severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1,
      81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and
      95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives,
      p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR:
      35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR:
      8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect
      CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with
      ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5%
      and 66.4%, respectively, with a referral rate of 43.8%. In women who tested
      positive for HR-HPV, sensitivity and specificity of dual-staining for detection
      of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%.
      CONCLUSIONS: p16/Ki-67 dual-stained cytology provided a high sensitivity and
      moderate specificity to detect underlying cervical precancer and cancers in
      various settings, and might be considered as an efficient screening tool in
      China.

PMID- 27029034
TI  - Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell
      renal cancer.
AB  - BACKGROUND: Genetic intratumoral heterogeneity (ITH) hinders biomarker
      development in metastatic clear cell renal cancer (mccRCC). Epigenetic relative
      to genetic ITH or the presence of consistent epigenetic changes following
      targeted therapy in mccRCC have not been evaluated. The aim of this study was to
      determine methylome/genetic ITH and to evaluate specific epigenetic and genetic
      changes associated with sunitinib therapy. PATIENTS AND METHODS: Multi-region DNA
      sampling performed on sequential frozen pairs of primary tumor tissue from 14
      metastatic ccRCC patients, in the Upfront Sunitinib (SU011248) Therapy Followed
      by Surgery in Patients with Metastatic Renal Cancer: a Pilot Phase II Study
      (SuMR; ClinicalTrials.gov identifier: NCT01024205), at presentation (biopsy) and
      after 3-cycles of 50mg sunitinib (nephrectomy). Untreated biopsy and nephrectomy
      samples before and after renal artery ligation were controls. Ion Proton
      sequencing of 48 key ccRCC genes, and MethylCap-seq DNA methylation analysis was
      performed, data was analysed using the statistical computing environment R.
      RESULTS: Unsupervised hierarchical clustering revealed complete methylome
      clustering of biopsy and three nephrectomy samples for each patient (14/14
      patients). For mutational status, untreated biopsy and all treated nephrectomy
      samples clustered together in 8/13 (61.5%) patients. The only methylation target
      significantly altered following sunitinib therapy was VHL promoter region 7896829
      which was hypermethylated with treatment (FDR=0.077, P<0.001) and consistent for
      all patients (pre-treatment 50% patients had VHL mutations, 14% patients VHL
      hypermethylation). Renal artery ligation did not affect this result. No
      significant differences in driver or private mutation count was found with
      sunitinib treatment. CONCLUSIONS: Demonstration of relative methylome homogeneity
      and consistent VHL hypermethylation, after sunitinib, may overcome the hurdle of
      ITH present at other molecular levels for biomarker research.

PMID- 27029035
TI  - Prognostic models to predict survival in patients with advanced non-small cell
      lung cancer treated with first-line chemo- or targeted therapy.
AB  - BACKGROUND: We aimed to assess the prognostic role of neutrophilia,
      lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design
      models to define the prognosis of patients receiving first-line chemo- or
      targeted therapy for advanced non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: We retrospectively analysed 401 consecutive patients with advanced NSCLC
      treated with first line chemo- or targeted therapy. Patients were stratified into
      two groups with pre-treatment NLR >= 3.7 (Group A) vs. < 3.7 (Group B). The best
      NLR cut-off was identified by ROC curve analysis. RESULTS: At baseline 264
      patients had NLR>=3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS
      was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS
      was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate
      analysis, ECOG-PS>=2, stage IV cancer, non-adenocarcinoma histology, EGFR wild
      type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR
      status and NLR>=3.7 were independent prognostic factors for worse PFS. Patients
      were stratified according to the presence of 0-1 prognostic factors (8%), 2-3
      factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7
      months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients
      were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2
      factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and
      3.3 months respectively (p < 0.001). CONCLUSIONS: Pre-treatment NLR is an
      independent prognostic factor for patients with advanced NSCLC treated with first
      line therapies.

PMID- 27029036
TI  - Routine clinical mutation profiling using next generation sequencing and a
      customized gene panel improves diagnostic precision in myeloid neoplasms.
AB  - Microscopic examination of myelodysplastic syndromes (MDS) and myelodysplastic
      myeloproliferative neoplasms (MDS/MPN) may be challenging because morphological
      features can overlap with those of reactive states. Demonstration of clonal
      hematopoiesis provides a diagnostic clue and has become possible by comprehensive
      mutation profiling of a number of frequently mutated genes, some of them with
      large coding regions.To emphasize the potential benefit of NGS in hematopathology
      we present sequencing results from routinely processed formalin-fixed and
      paraffin-embedded (FFPE) bone marrow trephines (n = 192). A customized amplicon
      based gene panel including 23 genes frequently mutated in myeloid neoplasms was
      established and implemented. Thereby, 629,691 reads per sample (range 179,847
      1,460,412) and a mean coverage of 2,702 (range 707-6,327) could be obtained,
      which are sufficient for comprehensive mutational profiling. Seven samples failed
      in sequencing (3.6%). In 185 samples we found in total 269 pathogenic variants
      (mean 1.4 variants per patient, range 0-5), 125 Patients exhibit at least one
      pathogenic mutation (67.6%). Variants show allele frequencies ranging from 6.7%
      up to 95.7%. Most frequently mutated genes were TET2 (28.7%), SRSF2 (19.5%),
      ASXL1 (8.6%) and U2AF1 (8.1%). The mutation profiling increases the diagnostic
      precision and adds prognostic information. 

PMID- 27029039
TI  - [The Right to Choose in Medical Rehabilitation in Germany].

PMID- 27029040
TI  - [Fear of Heights in Primary School Children].
AB  - The life-time prevalence of visual height intolerance in adults is 28 percent,
      whereas in primary school children, as recently shown, it develops in 34 percent.
      Triggers and symptoms are similar in children and adults. A significant
      difference in visual height intolerance of prepubertal children compared to
      adults is the good prognosis with mostly spontaneous remission within a few
      years, possibly facilitated by repeated exposure to the triggering situations. 

PMID- 27029038
TI  - Current perspectives between metabolic syndrome and cancer.
AB  - Metabolic syndrome is a cluster of risk factors that lead to cardiovascular
      morbidity and mortality. Recent studies linked metabolic syndrome and several
      types of cancer. Although metabolic syndrome may not necessarily cause cancer, it
      is linked to poorer cancer outcomes including increased risk of recurrence and
      overall mortality. This review tends to discuss the major biological and
      physiological alterations involved in the increase of incidence and mortality of
      cancer patients affected by metabolic syndrome. We focus on metabolic syndrome
      associated visceral adiposity, hyperinsulinemia, hyperglycemia, insulin-like
      growth factor (IGF-I) pathway as well as estrogen signaling and inflammation.
      Several of these factors are also involved in carcinogenesis and cancer
      progression. A better understanding of the link between metabolic syndrome and
      cancer may provide new insight about oncogenesis. Moreover, prevention of
      metabolic syndrome - related alterations may be an important aspect in the
      management of cancer patients during simultaneous palliative care.

PMID- 27029037
TI  - Signal transducer and activator of transcription 3 in myeloid-derived suppressor
      cells: an opportunity for cancer therapy.
AB  - Cancer progression is in part determined by interactions between cancer cells and
      stromal cells in the tumor microenvironment (TME). The identification of
      cytotoxic tumor-infiltrating lymphocytes has instigated research into immune
      stimulating cancer therapies. Although a promising direction, immunosuppressive
      mechanisms exerted at the TME hamper its success. Myeloid-derived suppressor
      cells (MDSCs) have come to the forefront as stromal cells that orchestrate the
      immunosuppressive TME. Consequently, this heterogeneous cell population has been
      the object of investigation. Studies revealed that the transcription factor
      signal transducer and activator of transcription 3 (STAT3) largely dictates the
      recruitment, activation and function of MDSCs in the TME. Therefore, this review
      will focus on the role of this key transcription factor during the MDSC's life
      cycle and on the therapeutic opportunities it offers.

PMID- 27029041
TI  - [Early Detection of Bipolar Disorders: Current State of the Art and Research
      Approaches].
AB  - Bipolar affective disorders (BD) are severe, recurrent and disabling disorders
      with devastating consequences for individuals, families and the society. Although
      this personal burden and costs for the health system provide a compelling
      rationale for development of early detection and early intervention strategies in
      BD, the development of at-risk criteria for BD is still in an early stage of
      research. In this paper we review the literature of clinical data that
      investigate at-risk criteria. Moreover, we will discuss methodological problems
      associated with the definition of being at high-risk for developing bipolar
      disorders and show the different research approaches that deal with the
      investigation of at-risk criteria and appropriate intervention for BD. If
      prospective studies confirm the at-risk criteria for BD, then there is potential
      to develop preventive measures in BD with opportunities to ameliorate the
      severity of or even prevent BD. 

PMID- 27029042
TI  - [Acute Psychosis after Consumption of Synthetic Cannabinoids].
AB  - INTRODUCTION: Mocarz is a Legal high that consists of dried parts of plants mixed
      with synthetic cannabinoids. There is currently limited information on its acute
      toxicity. CASE REPORT: We describe a 35-year-old patient with no previous medical
      and psychiatric history who was admitted to the psychiatric clinic after
      developing agitation and paranoid psychotic symptoms following the use of Mocarz
      purchased over the internet. CONCLUSION: Legal highs are a challenge in
      psychiatric acute care, because they provoke unpredictable mental states
      endangering self and others.

PMID- 27029043
TI  - [Not Available].

PMID- 27029044
TI  - [Not Available].

PMID- 27029045
TI  - [Substitution therapy with diamorphine].
AB  - After a long lead time the substitution with diamorphine was taken into the
      German catalogue of statutory health insurance in 2010. Currently about 570
      patients are treated this way in 9 ambulances in Germany. The study phase as well
      as the clinical practice are showing the success of this therapy concerning
      physical and mental health of patients and their circumstances of social life.
      Thereby substitution with diamorphine is underlying very strict admission
      criteria regarding patients on the one hand and particular organizational
      requirements of the medical institution on the other hand. This article explains
      these criteria in detail as well as neurobiological information and clinical
      workflow is presented. Improvement of mandatory requirements could lead to a
      better reaching of patients who benefit from substitution with diamorphine. 

PMID- 27029046
TI  - Historical Maps from Modern Images: Using Remote Sensing to Model and Map Century
      Long Vegetation Change in a Fire-Prone Region.
AB  - Understanding the age structure of vegetation is important for effective land
      management, especially in fire-prone landscapes where the effects of fire can
      persist for decades and centuries. In many parts of the world, such information
      is limited due to an inability to map disturbance histories before the
      availability of satellite images (~1972). Here, we describe a method for creating
      a spatial model of the age structure of canopy species that established pre-1972.
      We built predictive neural network models based on remotely sensed data and
      ecological field survey data. These models determined the relationship between
      sites of known fire age and remotely sensed data. The predictive model was
      applied across a 104,000 km(2) study region in semi-arid Australia to create a
      spatial model of vegetation age structure, which is primarily the result of stand
      replacing fires which occurred before 1972. An assessment of the predictive
      capacity of the model using independent validation data showed a significant
      correlation (rs = 0.64) between predicted and known age at test sites.
      Application of the model provides valuable insights into the distribution of
      vegetation age-classes and fire history in the study region. This is a relatively
      straightforward method which uses widely available data sources that can be
      applied in other regions to predict age-class distribution beyond the limits
      imposed by satellite imagery.

PMID- 27029047
TI  - Fully Automated Pulmonary Lobar Segmentation: Influence of Different Prototype
      Software Programs onto Quantitative Evaluation of Chronic Obstructive Lung
      Disease.
AB  - OBJECTIVES: Surgical or bronchoscopic lung volume reduction (BLVR) techniques can
      be beneficial for heterogeneous emphysema. Post-processing software tools for
      lobar emphysema quantification are useful for patient and target lobe selection,
      treatment planning and post-interventional follow-up. We aimed to evaluate the
      inter-software variability of emphysema quantification using fully automated
      lobar segmentation prototypes. MATERIAL AND METHODS: 66 patients with moderate to
      severe COPD who underwent CT for planning of BLVR were included. Emphysema
      quantification was performed using 2 modified versions of in-house software
      (without and with prototype advanced lung vessel segmentation; programs 1 [YACTA
      v.2.3.0.2] and 2 [YACTA v.2.4.3.1]), as well as 1 commercial program 3 [Pulmo3D
      VA30A_HF2] and 1 pre-commercial prototype 4 [CT COPD ISP ver7.0]). The following
      parameters were computed for each segmented anatomical lung lobe and the whole
      lung: lobar volume (LV), mean lobar density (MLD), 15th percentile of lobar
      density (15th), emphysema volume (EV) and emphysema index (EI). Bland-Altman
      analysis (limits of agreement, LoA) and linear random effects models were used
      for comparison between the software. RESULTS: Segmentation using programs 1, 3
      and 4 was unsuccessful in 1 (1%), 7 (10%) and 5 (7%) patients, respectively.
      Program 2 could analyze all datasets. The 53 patients with successful
      segmentation by all 4 programs were included for further analysis. For LV,
      program 1 and 4 showed the largest mean difference of 72 ml and the widest LoA of
      [-356, 499 ml] (p<0.05). Program 3 and 4 showed the largest mean difference of 4%
      and the widest LoA of [-7, 14%] for EI (p<0.001). CONCLUSIONS: Only a single
      software program was able to successfully analyze all scheduled data-sets.
      Although mean bias of LV and EV were relatively low in lobar quantification,
      ranges of disagreement were substantial in both of them. For longitudinal
      emphysema monitoring, not only scanning protocol but also quantification software
      needs to be kept constant.

PMID- 27029048
TI  - Maltose-Binding Protein (MBP), a Secretion-Enhancing Tag for Mammalian Protein
      Expression Systems.
AB  - Recombinant proteins are commonly expressed in eukaryotic expression systems to
      ensure the formation of disulfide bridges and proper glycosylation. Although many
      proteins can be expressed easily, some proteins, sub-domains, and mutant protein
      versions can cause problems. Here, we investigated expression levels of
      recombinant extracellular, intracellular as well as transmembrane proteins
      tethered to different polypeptides in mammalian cell lines. Strikingly, fusion of
      proteins to the prokaryotic maltose-binding protein (MBP) generally enhanced
      protein production. MBP fusion proteins consistently exhibited the most robust
      increase in protein production in comparison to commonly used tags, e.g., the Fc,
      Glutathione S-transferase (GST), SlyD, and serum albumin (ser alb) tag. Moreover,
      proteins tethered to MBP revealed reduced numbers of dying cells upon transient
      transfection. In contrast to the Fc tag, MBP is a stable monomer and does not
      promote protein aggregation. Therefore, the MBP tag does not induce artificial
      dimerization of tethered proteins and provides a beneficial fusion tag for
      binding as well as cell adhesion studies. Using MBP we were able to secret a
      disease causing laminin beta2 mutant protein (congenital nephrotic syndrome),
      which is normally retained in the endoplasmic reticulum. In summary, this study
      establishes MBP as a versatile expression tag for protein production in
      eukaryotic expression systems. 

PMID- 27029049
TI  - 11th International Podocyte Conference: Podocyte Biology in Glomerular Health and
      Disease. A Global Scientific Perspective. April 3-6, 2016, Haifa and Jerusalem,
      Israel: Abstracts.

PMID- 27029050
TI  - Combined DTI Tractography and Functional MRI Study of the Language Connectome in
      Healthy Volunteers: Extensive Mapping of White Matter Fascicles and Cortical
      Activations.
AB  - Despite a better understanding of brain language organization into large-scale
      cortical networks, the underlying white matter (WM) connectivity is still not
      mastered. Here we combined diffusion tensor imaging (DTI) fiber tracking (FT) and
      language functional magnetic resonance imaging (fMRI) in twenty healthy subjects
      to gain new insights into the macroscopic structural connectivity of language.
      Eight putative WM fascicles for language were probed using a deterministic DTI-FT
      technique: the arcuate fascicle (AF), superior longitudinal fascicle (SLF),
      uncinate fascicle (UF), temporo-occipital fascicle, inferior fronto-occipital
      fascicle (IFOF), middle longitudinal fascicle (MdLF), frontal aslant fascicle and
      operculopremotor fascicle. Specific measurements (i.e. volume, length, fractional
      anisotropy) and precise cortical terminations were derived for each WM fascicle
      within both hemispheres. Connections between these WM fascicles and fMRI
      activations were studied to determine which WM fascicles are related to language.
      WM fascicle volumes showed asymmetries: leftward for the AF, temporoparietal
      segment of SLF and UF, and rightward for the frontoparietal segment of the SLF.
      The lateralization of the AF, IFOF and MdLF extended to differences in patterns
      of anatomical connections, which may relate to specific hemispheric abilities.
      The leftward asymmetry of the AF was correlated to the leftward asymmetry of fMRI
      activations, suggesting that the lateralization of the AF is a structural
      substrate of hemispheric language dominance. We found consistent connections
      between fMRI activations and terminations of the eight WM fascicles, providing a
      detailed description of the language connectome. WM fascicle terminations were
      also observed beyond fMRI-confirmed language areas and reached numerous cortical
      areas involved in different functional brain networks. These findings suggest
      that the reported WM fascicles are not exclusively involved in language and might
      be related to other cognitive functions such as visual recognition, spatial
      attention, executive functions, memory, and processing of emotional and
      behavioral aspects. 

PMID- 27029051
TI  - Is hypothermia indicated during cardiopulmonary resuscitation and after
      restoration of spontaneous circulation?
AB  - PURPOSE OF REVIEW: Targeted temperature management (TTM) after cardiac arrest has
      become a standard therapy in postresuscitation care. However, many questions
      addressing the optimum treatment protocol remain unanswered. RECENT FINDINGS: The
      positive influence of intra-arrest cooling on survival and neurologic outcome,
      seen in animal studies, was not revealed in clinical trials so far. By contrast,
      the evidence of TTM after restoration of circulation is based on both
      experimental and clinical data. The mechanisms of cerebral injury unfold
      different time windows for cooling initiation. Immediate cooling and early
      achievement of a target temperature less than 34 degrees C seems to be
      beneficial, although clinical data on preclinical cooling failed to detect a
      positive correlation. Despite previous beneficial experimental and clinical data,
      the benefit of a lower body temperature was recently called into question by a
      recent study. Regardless of the preferred temperature range, the main focus must
      lie in active cooling and prevention of hyperthermic conditions. There are many
      factors that influence the effect of TTM, which should therefore be tailored to
      the specific patient's needs. SUMMARY: To maximize its beneficial potential, TTM
      should be customized to resuscitation covariates. Despite open questions on the
      optimum treatment protocol, active cooling should be started as soon as possible
      and hyperthermic conditions should be prevented in any case. To answer the
      question if intra-arrest cooling or prehospital cooling induction is indicated,
      additional studies are needed.

PMID- 27029052
TI  - Hard to Believe : Produced by Ken Stone and Irene Silber, 2015, Swoop Films and
      Stone Soup Productions (New York, 56 minutes, unrated).
AB  - This article presents a review of Hard to Believe, a compelling documentary
      reporting the forced organ procurement and death of Chinese prisoners of
      conscience. The documentary is targeted to ignite political and public pressure
      to stop these practices that are thought to be motivated by financial and
      political gain. Narrated by journalist and author Ethan Gutmann, the documentary
      pricks at the collective conscience, as credible witnesses provide evidence that
      point to an abrogation of every ethical principle ascribed to legitimate organ
      procurement. 

PMID- 27029053
TI  - What can imaging tell us about cognitive impairment and dementia?
AB  - Dementia is a contemporary global health issue with far reaching consequences,
      not only for affected individuals and their families, but for national and global
      socio-economic conditions. The hallmark feature of dementia is that of
      irreversible cognitive decline, usually affecting memory, and impaired activities
      of daily living. Advances in healthcare worldwide have facilitated longer life
      spans, increasing the risks of developing cognitive decline and dementia in late
      life. Dementia remains a clinical diagnosis. The role of structural and molecular
      neuroimaging in patients with dementia is primarily supportive role rather than
      diagnostic, American and European guidelines recommending imaging to exclude
      treatable causes of dementia, such as tumor, hydrocephalus or intracranial
      haemorrhage, but also to distinguish between different dementia subtypes, the
      commonest of which is Alzheimer's disease. However, this depends on the
      availability of these imaging techniques at individual centres. Advanced magnetic
      resonance imaging (MRI) techniques, such as functional connectivity MRI,
      diffusion tensor imaging and magnetic resonance spectroscopy, and molecular
      imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography
      (PET), amyloid PET, tau PET, are currently within the realm of dementia research
      but are available for clinical use. Increasingly the research focus is on earlier
      identification of at risk preclinical individuals, for example due to family
      history. Intervention at the preclinical stages before irreversible brain damage
      occurs is currently the best hope of reducing the impact of dementia. 

PMID- 27029054
TI  - Exosomes derived from gefitinib-treated EGFR-mutant lung cancer cells alter
      cisplatin sensitivity via up-regulating autophagy.
AB  - Several clinical trials indicate that concurrent administration of tyrosine
      kinase inhibitors (TKIs, such as gefitinib or erlotinib) with chemotherapy agents
      fails to improve overall survival in advanced non-small cell lung cancer (NSCLC)
      patients. However, the precise mechanisms underlying the antagonistic effects
      remain unclear. In the present study, we investigated the role of exosomes in the
      antagonistic effects of concurrent administration of chemotherapy and TKIs.
      Exosomes derived from gefitinib-treated PC9 cells (Exo-GF) decreased the
      antitumor effects of cisplatin, while exosomes derived from cisplatin-treated PC9
      cells (Exo-DDP) did not significantly affect the antitumor effects of gefitinib.
      Additionally, inhibition of exosome secretion by GW4869 resulted in a modest
      synergistic effect when cisplatin and gefitinib were co-administered.
      Furthermore, Exo-GF co-incubation with cisplatin increased autophagic activity
      and reduced apoptosis, as demonstrated by an upregulation of LC3-II and Bcl-2
      protein levels and downregulation of p62 and Bax protein levels. Thus, the
      antagonistic effects of gefitinib and cisplatin were mainly attributed to Exo-GF,
      which resulted in upregulated autophagy and increased cisplatin resistance. These
      results suggest that inhibition of exosome secretion may be a helpful strategy to
      overcome the antagonistic effects when TKIs and chemotherapeutic agents are co
      administered. Before administering chemotherapy, introducing a washout period to
      completely eliminate TKI-related exosomes, may be a better procedure for
      administering chemotherapy and TKIs. 

PMID- 27029055
TI  - Multifunctional targeting vinorelbine plus tetrandrine liposomes for treating
      brain glioma along with eliminating glioma stem cells.
AB  - Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery
      and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain
      barrier (BBB) restricts the movement of antitumor drugs from blood to brain, thus
      leading to the poor prognosis with high recurrence rate. In the present study,
      the targeting conjugates of cholesterol polyethylene glycol polyethylenimine
      (CHOL-PEG2000-PEI) and D-a-tocopheryl polyethylene glycol 1000 succinate
      vapreotide (TPGS1000-VAP) were newly synthesized for transporting drugs across
      the BBB and targeting glioma cells and GSCs. The multifunctional targeting
      vinorelbine plus tetrandrine liposomes were constructed by modifying the
      targeting conjugates. The studies were undertaken on BBB model, glioma cells,
      GSCs, and glioma-bearing mice. In vitro results showed that multifunctional
      targeting drugs-loaded liposomes with suitable physicochemical property could
      enhance the transport drugs across the BBB, increase the intracellular uptake,
      inhibit glioma cells and GSCs, penetrate and destruct the GSCs spheroids, and
      induce apoptosis via activating related apoptotic proteins. In vivo results
      demonstrated that multifunctional targeting drugs-loaded liposomes could
      significantly accumulate into brain tumor location, show the specificity to tumor
      sites, and result in a robust overall antitumor efficacy in glioma-bearing mice.
      These data suggested that the multifunctional targeting vinorelbine plus
      tetrandrine liposomes could offer a promising strategy for treating brain glioma.

PMID- 27029056
TI  - Treatment of newly diagnosed B-cell origin primary CNS lymphoma with systemic R
      IDARAM chemotherapy and intrathecal immunochemotherapy.
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare subtype of
      non-Hodgkin's lymphoma (NHL). The aim was to evaluate response rate, progression
      free survival (PFS), overall survival (OS), and toxicity in PCNSL after systemic
      R-IDARAM and intrathecal immunochemotherapy with deferred radiotherapy. RESULTS:
      The response rate was 94% with 17 (89%) complete responses and 1 (5%) partial
      responses. Follow-up time is from 5 to 63 months (median, 39 months). Median
      survival has not been reached. 3-year overall survival and progression-free
      survival rates were 84.2% (CI 72.6% to 99.8%) and 63.2% (CI 41.4% to 73.8%).
      Systemic toxicity was mainly hematologic. Neurocognitive and neuromotor
      deterioration as a result of treatment occurred in only one patient (5%).
      PATIENTS AND METHODS: From September 2010 to June 2015, 19 consecutive patients
      with PCNSL (median age, 54 years) were enrolled into a pilot phase II study
      evaluating immunochemotherapy without radiotherapy. The patients were accrued to
      a chemotherapy regimen that incorporated rituximab, idarubicin, dexamethasone,
      cytarabine (Ara-c) and methotrexate (MTX) combined with intrathecal rituximab,
      MTX, dexamethasone and Ara-c. CONCLUSIONS: The results indicate that R-IDARAM
      regimen with intrathecal immunochemotherapy is generally well tolerated and
      produces a high complete response rate and survival rate.

PMID- 27029057
TI  - Expression of epithelial-mesenchymal transition-related genes increases with copy
      number in multiple cancer types.
AB  - Epithelial-mesenchymal transition (EMT) is a cellular process through which
      epithelial cells transform into mesenchymal cells. EMT-implicated genes initiate
      and promote cancer metastasis because mesenchymal cells have greater invasive and
      migration capacities than epithelial cells. In this pan-cancer analysis, we
      explored the relationship between gene expression changes and copy number
      variations (CNVs) for EMT-implicated genes. Based on curated 377 EMT-implicated
      genes from the literature, we identified 212 EMT-implicated genes associated with
      more frequent copy number gains (CNGs) than copy number losses (CNLs) using data
      from The Cancer Genome Atlas (TCGA). Then by correlating these CNV data with TCGA
      gene expression data, we identified 71 EMT-implicated genes with concordant CNGs
      and gene up-regulation in 20 or more tumor samples. Of those, 14 exhibited such
      concordance in over 110 tumor samples. These 14 genes were predominantly
      apoptosis regulators, which may implies that apoptosis is critical during EMT.
      Moreover, the 71 genes with concordant CNG and up-regulation were largely
      involved in cellular functions such as phosphorylation cascade signaling. This is
      the first observation of concordance between CNG and up-regulation of specific
      genes in hundreds of samples, which may indicate that somatic CNGs activate gene
      expression by increasing the gene dosage. 

PMID- 27029058
TI  - Circulating tumor cells exhibit stem cell characteristics in an orthotopic mouse
      model of colorectal cancer.
AB  - The prognosis of colorectal cancer (CRC) is closely linked to the occurrence of
      distant metastases, which putatively develop from circulating tumor cells (CTCs)
      shed into circulation by the tumor. As far more CTCs are shed than eventually
      metastases develop, only a small subfraction of CTCs harbor full tumorigenic
      potential. The aim of this study was to further characterize CRC-derived CTCs to
      eventually identify the clinically relevant subfraction of CTCs.We established an
      orthotopic mouse model of CRC which reliably develops metastases and CTCs. We
      were able to culture the resulting CTCs in vitro, and demonstrated their tumor
      forming capacity when re-injected into mice. The CTCs were then subjected to qPCR
      expression profiling, revealing downregulation of epithelial and proliferation
      markers. Genes associated with cell-cell adhesion (claudin-7, CD166) were
      significantly downregulated, indicating a more metastatic phenotype of CTCs
      compared to bulk tumor cells derived from hepatic metastases. The stem cell
      markers DLG7 and BMI1 were significantly upregulated in CTC, indicating a stem
      cell-like phenotype and increased capacity of tumor formation and self-renewal.
      In concert with their in vitro and in vivo tumorigenicity, these findings
      indicate stem cell properties of mouse-derived CTCs.In conclusion, we developed
      an orthotopic mouse model of CRC recapitulating the process of CRC dissemination.
      CTCs derived from this model exhibit stem-cell like characteristics and are able
      to form colonies in vitro and tumors in vivo. Our results provide new insight
      into the biology of CRC-derived CTCs and may provide new therapeutic targets in
      the metastatic cascade of CRC. 

PMID- 27029059
TI  - A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates
      expansion of chronic lymphocytic leukemia cells.
AB  - The signaling lymphocyte activation molecule family [SLAMF] of cell surface
      receptors partakes in both the development of several immunocyte lineages and
      innate and adaptive immune responses in humans and mice. For instance, the
      homophilic molecule SLAMF6 (CD352) is in part involved in natural killer T cell
      development, but also modulates T follicular helper cell and germinal B cell
      interactions. Here we report that upon transplantation of a well-defined
      aggressive murine B220+CD5+ Chronic Lymphocytic Leukemia (CLL) cell clone, TCL1
      192, into SCID mice one injection of a monoclonal antibody directed against
      SLAMF6 (alphaSlamf6) abrogates tumor progression in the spleen, bone marrow and
      blood. Similarly, progression of a murine B cell lymphoma, LMP2A/lambdaMyc, was
      also eliminated by alphaSlamf6. But, surprisingly, alphaSLAMF6 neither eliminated
      TCL1-192 nor LMP2A/lambdaMyc cells, which resided in the peritoneal cavity or
      omentum. This appeared to be dependent upon the tumor environment, which affected
      the frequency of sub-populations of the TCL1-192 clone or the inability of
      peritoneal macrophages to induce Antibody Dependent Cellular Cytotoxicity (ADCC).
      However, co-administering alphaSlamf6 with the Bruton tyrosine kinase (Btk)
      inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the
      spleen, bone marrow, liver and the peritoneal cavity. Because an anti-human
      SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose
      that a combination of alphaSlamf6 with ibrutinib should be considered as a novel
      therapeutic approach for CLL and other B cell tumors. 

PMID- 27029060
TI  - Trichlorobenzene-substituted azaaryl compounds as novel FGFR inhibitors
      exhibiting potent antitumor activity in bladder cancer cells in vitro and in
      vivo.
AB  - In the present study, we examined the antitumor activity of a series of
      trichlorobenzene-substituted azaaryl compounds and identified MPT0L145 as a novel
      FGFR inhibitor with better selectivity for FGFR1, 2 and 3. It was preferentially
      effective in FGFR-activated cancer cells, including bladder cancer cell lines
      expressing FGFR3-TACC3 fusion proteins (RT-112, RT-4). MPT0L145 decreased the
      phosphorylation of FGFR1, FGFR3 and their downstream proteins (FRS2, ERK and
      Akt). Mechanistically, cDNA microarray analysis revealed that MPT0L145 decreased
      genes associated cell cycle progression, and increased genes associated with
      autophagy pathway. Accordingly, the data revealed that MPT0L145 induced G0/G1
      cell cycle arrest and decreased protein levels of cyclin E. Moreover, we provided
      the evidence that autophagy contributes to FGFR inhibitor-related cell death.
      Finally, MPT0L145 exhibited comparable antitumor activity to cisplatin with
      better safety in a RT-112 xenograft model. Taken together, these findings support
      the utility of MPT0L145 as a novel FGFR inhibitor, providing a strong rationale
      for further evaluation of this compound as a therapeutic agent for bladder
      cancers. 

PMID- 27029061
TI  - Lysine demethylase 2A promotes stemness and angiogenesis of breast cancer by
      upregulating Jagged1.
AB  - Alterations of histone methylation dynamically regulated by methyltransferases
      and demethylases are frequently found in human cancers. Here, we showed that
      expression of lysine demethylase 2A (KDM2A) is markedly increased in human breast
      cancer and its overexpression is associated with tumor progression and poor
      prognosis. Knockdown of KDM2A in breast cancer cells reduced proliferation but
      not viability. Gene set enrichment analysis revealed that inhibition of KDM2A
      down-regulates angiogenic genes with concurrent reduction of Jagged1 (JAG1),
      NOTCH1 and HEY1 in the NOTCH signaling. Chromatin immunoprecipitation-
      quantitative polymerase chain reaction (ChIP-qPCR) demonstrated the binding of
      KDM2A to the JAG1 promoter and the increase of methylation of Lys-36 of histone
      H3 (H3K36) in KDM2A-depleted MDA-MB-231 cells. Tumorsphere formation was
      significantly reduced in KDM2A-depleted cells which could be reversed by ectopic
      expression of JAG1. A selective KDM2A inhibitor daminozide also decreased the
      number of tumorsphere and the number of CD24-/CD44hi cells. In addition,
      daminozide acted synergistically with cisplatin in cell killing. We identified
      SOX2 as a direct transcriptional target of KDM2A to promote cancer stemness.
      Depletion of KDM2A in MDA-MB-231 cells attenuated NOTCH activation and tube
      formation in co-cultured endothelial cells. Two pro-angiogenic factors JAG1 and
      PDGFA are key mediators for KDM2A to enhance angiogenesis. Finally, inhibition of
      KDM2A significantly decreased tumor growth and angiogenesis in orthotopic animal
      experiments. Collectively, we conclude that KDM2A functions as an oncogene in
      breast cancer by upregulating JAG1 to promote stemness, chemoresistance and
      angiogenesis. 

PMID- 27029063
TI  - Peripheral lymphocyte subset variation predicts prostate cancer carbon ion
      radiotherapy outcomes.
AB  - The immune system plays a complementary role in the cytotoxic activity of
      radiotherapy. Here, we examined changes in immune cell subsets after heavy ion
      therapy for prostate cancer. The lymphocyte counts were compared with acute
      radiotherapy-related toxicity, defined according to the Common Terminology
      Criteria for Adverse Events, and short-term local efficacy, defined based on
      prostate-specific antigen concentrations. Confirmed prostate cancer patients who
      had not received previous radiotherapy were administered carbon ion radiotherapy
      (CIR) in daily fractions of 2.74 GyE with a total dose of 63-66 GyE. Lymphocyte
      subset counts were investigated before, during and after radiotherapy, and at a 1
      month follow-up. Most notable among our findings, the CD4/CD8 ratio and CD19+
      cell counts were consistently higher in patients with a complete response (CR) or
      partial response (PR) to CIR than in those classified in the stable disease (SD)
      group (P<0.05 for both). But CD3+ and CD8+ cell counts were lower in the CR and
      PR groups than in the SD group. These results indicate that variations in
      peripheral lymphocyte subpopulations are predictive of outcome after CIR for
      prostate cancer. 

PMID- 27029062
TI  - Targeting the chromatin remodeling enzyme BRG1 increases the efficacy of
      chemotherapy drugs in breast cancer cells.
AB  - Brahma related gene product 1 (BRG1) is an ATPase that drives the catalytic
      activity of a subset of the mammalian SWI/SNF chromatin remodeling enzymes. BRG1
      is overexpressed in most human breast cancer tumors without evidence of mutation
      and is required for breast cancer cell proliferation. We demonstrate that
      knockdown of BRG1 sensitized triple negative breast cancer cells to
      chemotherapeutic drugs used to treat breast cancer. An inhibitor of the BRG1
      bromodomain had no effect on breast cancer cell viability, but an inhibitory
      molecule that targets the BRG1 ATPase activity recapitulated the increased drug
      efficacy observed in the presence of BRG1 knockdown. We further demonstrate that
      inhibition of BRG1 ATPase activity blocks the induction of ABC transporter genes
      by these chemotherapeutic drugs and that BRG1 binds to ABC transporter gene
      promoters. This inhibition increased intracellular concentrations of the drugs,
      providing a likely mechanism for the increased chemosensitivity. Since ABC
      transporters and their induction by chemotherapy drugs are a major cause of
      chemoresistance and treatment failure, these results support the idea that
      targeting the enzymatic activity of BRG1 would be an effective adjuvant therapy
      for breast cancer. 

PMID- 27029064
TI  - ImmunoPET helps predicting the efficacy of antibody-drug conjugates targeting
      TENB2 and STEAP1.
AB  - The efficacy of antibody-drug conjugates (ADCs) targeted to solid tumors depends
      on biological processes that are hard to monitor in vivo. 89Zr-immunoPET of the
      ADC antibodies could help understand the performance of ADCs in the clinic by
      confirming the necessary penetration, binding, and internalization. This work
      studied monomethyl auristatin E (MMAE) ADCs against two targets in metastatic
      castration-resistant prostate cancer, TENB2 and STEAP1, in four patient-derived
      tumor models (LuCaP35V, LuCaP70, LuCaP77, LuCaP96.1). Three aspects of ADC
      biology were measured and compared: efficacy was measured in tumor growth
      inhibition studies; target expression was measured by immunohistochemistry and
      flow cytometry; and tumor antibody uptake was measured with 111In-mAbs and gamma
      counting or with 89Zr-immunoPET. Within each model, the mAb with the highest
      tumor uptake showed the greatest potency as an ADC. Sensitivity between models
      varied, with the LuCaP77 model showing weak efficacy despite high target
      expression and high antibody uptake. Ex vivo analysis confirmed the in vivo
      results, showing a correlation between expression, uptake and ADC efficacy. We
      conclude that 89Zr-immunoPET data can demonstrate which ADC candidates achieve
      the penetration, binding, and internalization necessary for efficacy in tumors
      sensitive to the toxic payload. 

PMID- 27029065
TI  - The feasibility of 18F-AlF-NOTA-PRGD2 PET/CT for monitoring early response of
      Endostar antiangiogenic therapy in human nasopharyngeal carcinoma xenograft model
      compared with 18F-FDG.
AB  - PURPOSE: Radiolabeled arginine-glycine-aspartic acid (RGD) peptides have been
      developed for PET imaging of integrin avbeta3 in the tumor vasculature, leading
      to great potential for noninvasively evaluating tumor angiogenesis and monitoring
      antiangiogenic treatment. The aim of this study was to investigate a novel one
      step labeled integrin-targeted tracer, 18F-AlF-NOTA-PRGD2, for PET/CT for
      detecting tumor angiogenesis and monitoring the early therapeutic efficacy of
      antiangiogenic agent Endostar in human nasopharyngeal carcinoma (NPC) xenograft
      model. EXPERIMENTAL DESIGN AND RESULTS: Mice bearing NPC underwent 18F-AlF-NOTA
      PRGD2 PET/CT at baseline and after 2, 4, 7, and 14 days of consecutive treatment
      with Endostar or PBS, compared with 18F-FDG PET/CT. Tumors were harvested at all
      imaging time points for histopathological analysis with H & E and microvessel
      density (MVD) and integrin avbeta3 immunostaining. The maximum percent injected
      dose per gram of body weight (%ID/gmax) tumor uptake of 18F-AlF-NOTA-PRGD2 PET/CT
      was significantly lower than that in the control group starting from day 2 (p <
      0.01), much earlier and more accurately than that of 18F-FDG PET/CT. Moreover, a
      moderate linear correlation was observed between tumor MVD and the corresponding
      tumor uptake of 18F-AlF-NOTA-PRGD2 PET/CT (r = 0.853, p < 0.01). CONCLUSIONS: 18F
      AlF-NOTA-PRGD2 PET/CT can be used for in vivo angiogenesis imaging and monitoring
      early response to Endostar antiangiogenic treatment in NPC xenograft model,
      favoring its potential clinical translation.

PMID- 27029066
TI  - High-Performance Protonic Ceramic Fuel Cells with Thin-Film Yttrium-Doped Barium
      Cerate-Zirconate Electrolytes on Compositionally Gradient Anodes.
AB  - In this study, we used a compositionally gradient anode functional layer (AFL)
      consisting of Ni-BaCe(0.5)Zr(0.35)Y(0.15)O(3-delta) (BCZY) with increasing BCZY
      contents toward the electrolyte-anode interface for high-performance protonic
      ceramic fuel cells. It is identified that conventional homogeneous AFLs fail to
      stably accommodate a thin film of BCZY electrolyte. In contrast, a dense 2 MUm
      thick BCZY electrolyte was successfully deposited onto the proposed gradient AFL
      with improved adhesion. A fuel cell containing this thin electrolyte showed a
      promising maximum peak power density of 635 mW cm(-2) at 600  degrees C, with an
      open-circuit voltage of over 1 V. Impedance analysis confirmed that minimizing
      the electrolyte thickness is essential for achieving a high power output,
      suggesting that the anode structure is important in stably accommodating thin
      electrolytes.

PMID- 27029068
TI  - PILRalpha binds an unknown receptor expressed primarily on CD56bright and
      decidual-NK cells and activates NK cell functions.
AB  - Natural Killer (NK) cells are innate immune lymphocytes specializing in
      recognition and killing of tumors and pathogens, using an array of activating and
      inhibitory receptors. NK inhibition is mediated by a large repertoire of
      inhibitory receptors, whereas a limited number of activating NK cell receptors
      execute NK cell activation. The ligands recognized by the activating receptors
      are stress-induced, pathogen derived, tumor specific and even self ligands.
      However, the full spectrum of NK cell receptors and ligands that control NK cell
      activity remains uncharacterized. Here we demonstrate that Paired Ig-Like type 2
      Receptor Alpha (PILRalpha), binds a distinct human NK cell sub-population present
      in the peripheral blood and also in the decidua. We further demonstrate that the
      interaction of NK cells with PILRalpha expressing targets lead to elevated
      IFNgamma secretion and cytotoxicity. In conclusion, we present here a novel NK
      activating ligand which binds and activates an unknown NK receptor expressed on a
      unique NK cell subset.

PMID- 27029069
TI  - C3 deficiency ameliorates the negative effects of irradiation of the young brain
      on hippocampal development and learning.
AB  - Radiotherapy in the treatment of pediatric brain tumors is often associated with
      debilitating late-appearing adverse effects, such as intellectual impairment.
      Areas in the brain harboring stem cells are particularly sensitive to irradiation
      (IR) and loss of these cells may contribute to cognitive deficits. It has been
      demonstrated that IR-induced inflammation negatively affects neural progenitor
      differentiation. In this study, we used mice lacking the third complement
      component (C3-/-) to investigate the role of complement in a mouse model of IR
      induced injury to the granule cell layer (GCL) of the hippocampus. C3-/- and wild
      type (WT) mice received a single, moderate dose of 8 Gy to the brain on postnatal
      day 10. The C3-/- mice displayed 55 % more microglia (Iba-1+) and a trend towards
      increase in proliferating cells in the GCL compared to WT mice 7 days after IR.
      Importantly, months after IR C3-/- mice made fewer errors than WT mice in a
      reversal learning test indicating better learning capacity in C3-/- mice after
      IR. Notably, months after IR C3-/- and WT mice had similar GCL volumes, survival
      of newborn cells (BrdU), microglia (Iba-1) and astrocyte (S100beta) numbers in
      the GCL. In summary, our data show that the complement system contributes to IR
      induced loss of proliferating cells and maladaptive inflammatory responses in the
      acute phase after IR, leading to impaired learning capacity in adulthood.
      Targeting the complement system is hence promising for future strategies to
      reduce the long-term adverse consequences of IR in the young brain. 

PMID- 27029067
TI  - Neuraminidase-1: a novel therapeutic target in multistage tumorigenesis.
AB  - Several of the growth factors and their receptor tyrosine kinases (RTK) such as
      epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast
      growth factor (FGF), vascular endothelial growth factor (VEGF), nerve growth
      factor (NGF) and insulin are promising candidate targets for cancer therapy.
      Indeed, tyrosine kinase inhibitors (TKI) have been developed to target these
      growth factors and their receptors, and have demonstrated dramatic initial
      responses in cancer therapy. Yet, most patients ultimately develop TKI drug
      resistance and relapse. It is essential in the clinical setting that the targeted
      therapies are to circumvent multistage tumorigenesis, including genetic mutations
      at the different growth factor receptors, tumor neovascularization,
      chemoresistance of tumors, immune-mediated tumorigenesis and the development of
      tissue invasion and metastasis. Here, we identify a novel receptor signaling
      platform linked to EGF, NGF, insulin and TOLL-like receptor (TLR) activations,
      all of which are known to play major roles in tumorigenesis. The importance of
      these findings signify an innovative and promising entirely new targeted therapy
      for cancer. The role of mammalian neuraminidase-1 (Neu1) in complex with matrix
      metalloproteinase-9 and G protein-coupled receptor tethered to RTKs and TLRs is
      identified as a major target in multistage tumorigenesis. Evidence exposing the
      link connecting growth factor-binding and immune-mediated tumorigenesis to this
      novel receptor-signaling paradigm will be reviewed in its current relationship to
      cancer.

PMID- 27029070
TI  - Loss of PIG3 increases HIF-1alpha level by promoting protein synthesis via mTOR
      pathway in renal cell carcinoma cells.
AB  - PIG3 is a target of the tumor suppressor p53 and is thought to be involved in p53
      mediated cell apoptosis. Although PIG3 is similar to oxidoreductases involved in
      generating ROS, whether PIG3 would regulate HIF-1alpha was never characterized
      directly. Here we demonstrated that knockdown of PIG3 by transfecting with
      specific siRNA could increase the expression of HIF-1alpha in several human
      cancer cell lines, including CAKI, FTC-133 and A549. It indicates that PIG3 may
      be involved in the regulation of HIF-1alpha. Furthermore, we revealed that PIG3
      siliencing increased HIF-1alpha protein level through promoting its protein
      biosynthesis via mTOR pathway. In addition, the effect of PIG3 on the production
      of HIF-1alpha was further related to VEGF secretion and cell migration. PIG3
      downregulation increased the secretion of VEGF and promoted the migration of
      renal cancer cells obviously. Taken together, these data suggest that PIG3 was
      involved in HIF-1alpha regulation, and reveal a novel signaling pathway of
      PIG3/HIF-1alpha in the regulation of cell migration in renal cell carcinoma. 

PMID- 27029071
TI  - TRPV4 channels regulate tumor angiogenesis via modulation of Rho/Rho kinase
      pathway.
AB  - Targeting angiogenesis is considered a promising therapy for cancer. Besides
      curtailing soluble factor mediated tumor angiogenesis, understanding the
      unexplored regulation of angiogenesis by mechanical cues may lead to the
      identification of novel therapeutic targets. We have recently shown that
      expression and activity of mechanosensitive ion channel transient receptor
      potential vanilloid 4 (TRPV4) is suppressed in tumor endothelial cells and
      restoring TRPV4 expression or activation induces vascular normalization and
      improves cancer therapy. However, the molecular mechanism(s) by which TRPV4
      modulates angiogenesis are still in their infancy. To explore how TRPV4 regulates
      angiogenesis, we have employed TRPV4 null endothelial cells (TRPV4KO EC) and
      TRPV4KO mice. We found that absence of TRPV4 (TRPV4KO EC) resulted in a
      significant increase in proliferation, migration, and abnormal tube formation in
      vitro when compared to WT EC. Concomitantly, sprouting angiogenesis ex vivo and
      vascular growth in vivo was enhanced in TRPV4KO mice. Mechanistically, we
      observed that loss of TRPV4 leads to a significant increase in basal Rho activity
      in TRPV4KO EC that corresponded to their aberrant mechanosensitivity on varying
      stiffness ECM gels. Importantly, pharmacological inhibition of the Rho/Rho kinase
      pathway by Y-27632 normalized abnormal mechanosensitivity and angiogenesis
      exhibited by TRPV4KO EC in vitro. Finally, Y-27632 treatment increased pericyte
      coverage and in conjunction with Cisplatin, significantly reduced tumor growth in
      TRPV4KO mice. Taken together, these data suggest that TRPV4 regulates
      angiogenesis endogenously via modulation of EC mechanosensitivity through the
      Rho/Rho kinase pathway and can serve as a potential therapeutic target for cancer
      therapy. 

PMID- 27029072
TI  - HDAC1 controls CIP2A transcription in human colorectal cancer cells.
AB  - This work describes the effectiveness of HDAC-inhibitor (S)-2 towards colorectal
      cancer (CRC) HCT116 cells in vitro by inducing cell cycle arrest and apoptosis,
      and in vivo by contrasting tumour growth in mice xenografts. Among the
      multifaceted drug-induced events described herein, an interesting link has
      emerged between the oncoprotein histone deacetylase HDAC1 and the oncogenic
      Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) which is overexpressed in
      several cancers including CRCs. HDAC1 inhibition by (S)-2 or specific siRNAs
      downregulates CIP2A transcription in three different CRC cell lines, thus
      restoring the oncosuppressor phosphatase PP2A activity that is reduced in most
      cancers. Once re-activated, PP2A dephosphorylates pGSK-3beta(ser9) which
      phosphorylates beta-catenin that remains within the cytosol where it undergoes
      degradation. The decreased amount/activity of beta-catenin transcription factor
      prompts cell growth arrest by diminishing c-Myc and cyclin D1 expression and
      abrogating the prosurvival Wnt/beta-catenin signaling pathway. These results are
      the first evidence that the inhibition of HDAC1 by (S)-2 downregulates CIP2A
      transcription and unleashes PP2A activity, thus inducing growth arrest and
      apoptosis in CRC cells. 

PMID- 27029073
TI  - Combination of an anti-EGFRvIII antibody CH12 with Rapamycin synergistically
      inhibits the growth of EGFRvIII+PTEN-glioblastoma in vivo.
AB  - There are still unmet medical needs for the treatment of glioblastoma (GBM), the
      most frequent and aggressive brain tumor worldwide. EGFRvIII, overexpressed in
      approximately 30% of GBM, has been regarded as a potential therapeutic target. In
      this study, we demonstrated that CH12, an anti-EGFRvIII monoclonal antibody,
      could significantly suppress the growth of EGFRvIII+ GBM in vivo; however, PTEN
      deficiency in GBM reduced the efficacy of CH12 by attenuating its effect on
      PI3K/AKT/mTOR pathway. To overcome this problem, CH12 was combined with the mTOR
      inhibitor rapamycin, leading to a synergistic inhibitory effect on EGFRvIII+PTEN-
      GBM in vivo. Mechanistically, the synergistic antitumor effect was achieved via
      attenuating EGFR and PI3K/AKT/mTOR pathway more effectively and reversing the
      STAT5 activation caused by rapamycin treatment. Moreover, the combination therapy
      suppressed angiogenesis and induced cancer cell apoptosis more efficiently.
      Together, these results indicated that CH12 and rapamycin could synergistically
      suppress the growth of EGFRvIII+PTEN- GBM, which might have a potential clinical
      application in the future. 

PMID- 27029074
TI  - Preventive and therapeutic effects of thymosin beta4 N-terminal fragment Ac-SDKP
      in the bleomycin model of pulmonary fibrosis.
AB  - In this study, the bleomycin model of pulmonary fibrosis was utilized to
      investigate putative anti-fibrotic activity of Ac-SDKP in vivo. Male CD-1 mice
      received intra-tracheal bleomycin (BLEO, 1 mg/kg) instillation in the absence or
      presence of Ac-SDKP (a dose of 0.6 mg/kg delivered intra-peritoneally on the day
      of BLEO treatment, d0, followed by bi-weekly additional doses). To evaluate
      therapeutic effects in a subset of mice, Ac-SDKP was administered one week after
      BLEO instillation (d7). Animals were sacrificed at one, two, or three weeks
      later. Measurement of fluid and collagen content in the lung, Broncho Alveolar
      Lavage Fluid (BALF) analysis, lung histology, immunohistochemistry (IHC), and
      molecular analysis were performed. Compared to BLEO-treated mice, animals that
      received also Ac-SDKP (at both d0 and d7) had significantly decreased mortality,
      weight loss, inflammation (edema, and leukocyte lung infiltration), lung damage
      (histological evidence of lung injury), and fibrosis (collagen histological
      staining and soluble collagen content in the lung) at up to 21 days. Moreover,
      IHC and quantitative RT-PCR results demonstrated a significant decrease in BLEO
      induced IL-17 and TGF-beta expression in lung tissue. Importantly, alpha-SMA
      expression, the hallmark of myofibroblast differentiation, was also decreased.
      This is the first report showing not only a preventive protective role of Ac-SDKP
      but also its significant therapeutic effects in the bleomycin model of pulmonary
      fibrosis, thus supporting further preclinical and clinical studies. 

PMID- 27029075
TI  - Effect of tumor necrosis factor-alpha induced protein 8 like-2 on immune function
      of dendritic cells in mice following acute insults.
AB  - Tumor necrosis factor-alpha induced protein 8 like-2 (TNFAIP8L2, TIPE2) is a
      lately discovered negative regulator of innate immunity and cellular immunity.
      The present study was designed to investigate whether naturally occurring
      dendritic cells (DCs) could express TIPE2 mRNA/protein and its potential
      significance. Expressions of co-stimulatory molecules on DC surface and cytokines
      were analyzed to assess the functional role of TIPE2 in controlling DC maturation
      as well as activation. The activated DCs were assessed for their capacity to
      stimulate the proliferation and differentiation of T cells. It was found that
      TIPE2 was a cytoplasmic protein expressed in DCs, and the percentage of DCs which
      expressed co-stimulatory molecules and cytokines were obviously up-regulated when
      TIPE2 gene silenced by siRNA in vitro and in vivo. DCs undergone TIPE2 knockdown
      were found to promote the maturation of DCs, T-cell proliferation as well as
      differentiation, and they were significantly elevated IL-2 level and intranuclear
      NF-AT activation. Conversely, in over-expressing TIPE2 DC cells, it could inhibit
      T-cell proliferation and differentiation, and markedly down-regulate IL-2
      expression and intranuclear NF-AT activation after scald injury. The results
      suggested that TIPE2 appeared to be a critical immunoregulatory molecule which
      affected DC maturation and subsequent T-cell mediated immunity. 

PMID- 27029076
TI  - Sitagliptin use and thyroid cancer risk in patients with type 2 diabetes.
AB  - Whether sitagliptin may increase thyroid cancer risk has not been investigated in
      the Asian populations. This study evaluated the association in Taiwanese patients
      with newly diagnosed type 2 diabetes from 1999 to 2008 by using the reimbursement
      database of the National Health Insurance. They should have been followed for at
      least 6 months after March 1, 2009, the date when sitagliptin was approved for
      reimbursement. Patients newly treated with sitagliptin (n=58238, "ever users of
      sitagliptin") or other antidiabetic drugs (n =312853, "never users of
      sitagliptin") were followed until December 31, 2011. The treatment effect (for
      ever versus never users, and for tertiles of cumulative duration of therapy) was
      estimated by Cox regression incorporated with the inverse probability of
      treatment weighting using propensity score. Results showed that the respective
      number of incident thyroid cancer in ever users and never users was 28 and 172,
      with respective incidence of 29.34 and 22.13 per 100,000 person-years. The
      overall hazard ratio (95% confidence interval) of 1.516 (1.011-2.271) suggested a
      significantly higher risk associated with sitagliptin use. In tertile analyses,
      the hazard ratio for the first ( < 6.53 months), second (6.53-14.00 months) and
      third ( > 14 months) tertile of cumulative duration was 1.995 (1.015-3.919),
      2.516 (1.451-4.364) and 0.595 (0.244-1.449), respectively. Analyses after
      excluding patients with benign thyroid disease and in a subsample matched on
      baseline characteristics supported the findings in the original sample. In
      conclusion, sitagliptin use is associated with an increased risk of thyroid
      cancer, especially during the first year of its treatment. 

PMID- 27029077
TI  - Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via
      inhibiting methylation of the keap1 gene promoter region.
AB  - Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1
      promoter, which decreases Keap1 mRNA and protein expression levels, thus
      impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio
      resistance. In this study, we showed that genistein selectively exhibited a
      radiosensitizing effect on NSCLC A549 cells but not on normal lung fibroblast MRC
      5 cells. Genistein caused oxidative stress in A549 cells rather than MRC-5 cells,
      as determined by the oxidation of the ROS-sensitive probe DCFH-DA and oxidative
      damage marked by MDA, PCO or 8-OHdG content. In A549 instead of MRC-5 cells,
      genistein reduced the level of methylation in the Keap1 promoter region, leading
      to an increased mRNA expression, thus effectively inhibited the transcription of
      Nrf2 to the nucleus, which suppressed the Nrf2-dependent antioxidant and resulted
      in the upregulation of ROS. Importantly, when combined with radiation, genistein
      further increased the ROS levels in A549 cells whereas decreasing the radiation
      induced oxidative stress in MRC-5 cells, possibly via increasing the expression
      levels of Nrf2, GSH and HO-1. Moreover, radiation combined with genistein
      significantly increased cell apoptosis in A549 but not MRC-5 cells. Together, the
      results herein show that the intrinsic difference in the redox status of A549 and
      MRC-5 cells could be the target for genistein to selectively sensitize A549 cells
      to radiation, thereby leading to an increase in radiosensitivity for A549 cells. 

PMID- 27029078
TI  - The genetic difference between Western and Chinese urothelial cell carcinomas:
      infrequent FGFR3 mutation in Han Chinese patients.
AB  - Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC),
      renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies
      dependent on geographical areas and tumor locations, which indicates different
      oncogenic mechanisms and/or different genetic susceptibility/environment
      exposure. The activating mutations of the fibroblast growth factor receptor 3
      (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most
      frequent genetic events in UCCs. These mutations have clinical utilities in UCC
      initial diagnostics, prognosis, recurrence monitoring and management. However,
      the vast majority of the results are obtained from studies of UCC patients in
      Western countries, and little has been known about these in Han Chinese patients.
      In the present study, we screened the FGFR3 gene and TERT promoter for mutations
      in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger
      Sequencing. TERT promoter mutations occurred at a high frequency in these UCC
      patients, comparable with that seen in Western patients, however, the FGFR3
      mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for
      UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the
      pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy
      have limited clinical utility in these patients. Our results underscore the need
      for extensive characterization of cancer genomes from diverse patient
      populations, thereby contributing to precision medicine for cancer treatment and
      prevention. 

PMID- 27029079
TI  - [THE NEW CONCEPT OF COMBINED USE OF EXTRACORPOREAL BLOOD CORRECTION IN COMPLEX
      INTENSIVE THERAPY OF SEVERE SEPSIS IN PATIENTS AFTER CARDIAC SURGERY].
AB  - OBJECTIVE: Clinical and laboratory evaluation of the safety and efficacy of
      combined application of LPS selective adsorption (using cartridges with
      immobilized polymyxin B on fibers) and plasma filtration and adsorption (CPFA) in
      patients with severe sepsis after surgery on the heart and blood vessels.
      MATERIAL AND METHODS: The study involved 40 adult patients with severe sepsis
      after cardiac surgery. Group I included 20 patients who received the combined
      therapy with LPS-selective adsorption and CPFA in a single circuit. The control
      group 2 consisted of 20 patients who received the standard complex intensive
      therapy of sepsis. Inclusion criteria were clinical and laboratory indices of
      sepsis (FAA endotoxin activity level above 0.6; procalcitonin 2 ng/ml). RESULTS:
      Patients in Group I had an increase in mean aerial pressure by 12% (p = 0.001),
      the oxygenation index of 36% (p = 0.004), leukocytosis reduction (p = 0.01) and a
      significant decrease in body temperature (p = 0.0001). We also registered
      declines of FAA endotoxin activity by 35% (p = 0.0003) and Procalcitonin by 55%
      (p = 0.005). Patients of the control group had no significant change in the level
      of white blood cells, procalcitonin, and temperature. 28-day survival rate was 65
      and 35% in the 1st and 2nd groups, respectively (p = 0.11). CONCLUSION:
      Combination of LPS adsorption and CPFA in a single extracorporeal circuit in the
      complex intensive therapy is a safe and effective treatment of severe sepsis.

PMID- 27029080
TI  - Medicaid and Children's Health Insurance Programs; Mental Health   Parity and
      Addiction Equity Act of 2008; the Application of Mental   Health Parity
      Requirements to Coverage Offered by Medicaid Managed Care Organizations, the
      Children's Health Insurance Program (CHIP), and Alternative Benefit Plans. Final
      rule.
AB  - This final rule will address the application of certain requirements set forth in
      the Public Health Service Act, as amended by the Paul Wellstone and Pete Domenici
      Mental Health Parity and Addiction Equity Act of 2008, to coverage offered by
      Medicaid managed care organizations, Medicaid Alternative Benefit Plans, and
      Children's Health Insurance Programs.

PMID- 27029081
TI  - Author Reply.

PMID- 27029082
TI  - The therapeutic agents that target ATP-sensitive potassium  channels.
AB  - ATP-sensitive potassium (K(ATP)) channels are a major drug target for the
      treatment of type-2 diabetes. K(ATP) channels are ubiquitously expressed and link
      the metabolic state to electrical excitability. In pancreatic beta-cells, K(ATP)
      channels are crucial in the regulation of glucose-induced insulin secretion.
      Also, K(ATP) channels are involved in the protection against neuronal seizures
      and ischaemic stress in the heart, brain and in the regulation of vascular smooth
      muscle tone. Functional K(ATP) channels are hetero-octamers composed of two
      subunits, a pore forming Kir6, which is a member of the inwardly rectifying
      potassium channels family, and a regulatory sulphonylurea receptor (SUR). In
      response to nucleotides and pharmaceutical agonists and antagonists, SUR
      allosterically regulates channel gating. The allosteric communication pathways
      between these two heterologus proteins in K(ATP) channels are still poorly
      understood. This review will highlight the therapeutic agents that target K(ATP)
      channels and are used to treat diabetes and cardiovascular diseases.

PMID- 27029083
TI  - Forever Orthodontics.

PMID- 27029084
TI  - Pearls from Dr. Larry White.

PMID- 27029085
TI  - Controlled, Rapid Uprighting of Molars: A surprisingly Simple Solution The Pivot
      Arm Appliance.
AB  - In orthodontic cases where the regional anatomy provides limited room for
      eruption, there is etiologically a higher occurrence of tipped/impacted second
      molars. Although second molar extraction with third molar replacement is a useful
      option, the "Pivot Arm Appliance" encourages the uprighting of the second molar
      as a preferred treatment. The most unique and important attribute of the "Pivot
      Arm Appliance" is the rotating tube. In cases of access limitation, the disto
      occlusal surface of the molar presents as one area that is accessible. Other
      features of the "Pivot Arm Appliance" include: The position of the rotator tube
      delivers optimal rotational force through the pivoting action of the tube/arm
      complex. The "Pivot Arm Appliance" takes advantage of the efficiency and
      simplicity of a Class I lever system. The anatomical fulcrum being the dense
      cortical bone located anterior to the ascending ramus. The vertical spring system
      is compact, reliable and delivers gentle controlled force in rotational
      direction. The lingual location of the "Pivot Arm Appliance" does not hinder the
      function of the tongue, impinge on the soft tissue or interfere with normal
      masticatory function. The ease of placement of the rotator tube and subsequent
      insertion of the spring. It is well to note the uprighting appliance provides a
      very useful and practical approach to the unique problem of severely tipped
      second molars with limited buccal access. The "Pivot Arm Appliance" does not
      function only in these situations but can be used in all cases of second molar
      uprighting of a moderate to severe nature.

PMID- 27029086
TI  - Interdisciplinary Approach for Management of Congenitally Missing Maxillary
      Lateral Incisors: A Case Report.
AB  - Maxillary lateral incisors are frequently found congenitally missing, and their
      replacement has to be done prosthodontically. However, there are a variety of
      treatment options; a justified solution after orthodontic correction is the use
      of Maryland Bridges. Following is a case report of congenitally missing maxillary
      lateral incisors and an impacted canine and their orthodontic correction followed
      by prosthetic replacement of the lateral incisors using Maryland bridges.

PMID- 27029087
TI  - Correction of a Overjet and Overbite In Class II Division 1 Malocclusion Using
      Twin Block Appliance Therapy: A Case Report.
AB  - Class II division 1 malocclusion is the most common malocclusion. It shows
      specific clinical characteristics such as large overiet and deep overbite
      resulting in a soft tissue profile imbalance. Majority of the patients with class
      II division 1 malocclusions have an underlying skeletal discrepancy between the
      maxilla and mandible. The treatment of skeletal class II division 1 malocclusion
      is done taking into consideration the age, growth potential, severity of
      malocclusion, and compliance of patient with treatment. Myofunctional appliances
      can be successfully used to treat growing patients with class II division 1
      malocclusion. This article presents a discussion on successful treatment of class
      II division 1 malocclusion with growth modification approach using twin block
      appliances.

PMID- 27029088
TI  - Orthodontics in the "Art" of Aesthetics.
AB  - Aesthetics in dentistry has of late become an awakening/actor among patients and
      often serves as a major reason for seeking dental treatment and care. Ever since
      the introduction of orthodontics as a separate specialty branch in dentistry, a
      variety of techniques have evolved, and methods developed both in the type of
      devices/instruments used and treatments planned. The discipline of orthodontic
      aesthetics involves micro and macro aesthetics, gingival, and facial aesthetics.
      This article helps focus on the artistic part of the orthodontic science. It
      brings out various important factors involved in customizing aesthetic
      orthodontic treatment planning according to the individual needs of the patient.
      Through this kind of treatment planning not only are the functional and
      biological needs of the patient met, they also provide a stable and durable
      results. Less invasive treatment planning makes it easier for the patient to
      select future treatment options as new technologies keep evolving. The review was
      selected by typing aesthetic orthodontics in the Google search engine, Pubmed,
      and Pubmed Central. Literature review of articles reflecting history, different
      analysis, factors responsible, and the latest technique was conducted.

PMID- 27029089
TI  - Anterior Crossbite and Crowding Correction with a Series of Clear Aligners
      Involving Lower Incisor Extraction: "The Clear Way" Case Report.
AB  - The Clear Aligner can be used to correct tooth movement without involving
      extraction, surgery, and other adjunct orthopaedic appliances. Some forms
      ofattachments are required with clear aligners to achieve all major types of
      orthodontic tooth movements. The Clear Aligner is a procedure that can be
      performed by a clinician with computer simulation/calculation. Since the Clear
      Aligner can be fabricated in steps, it is readily available to change the
      treatment sequence throughout the course of the treatment in cases of complex
      malocclusions. The patient can receive any necessary dental procedures with ease
      during the course of the treatment. The treatment can also be easily resumed even
      if the patient has not worn the aligners for a period of time. The purpose of
      this article is to report dental anterior crossbite correction with a series of
      Clear Aligners without the use of any forms of attachments. The Clear Aligner
      could be used as an alternative in appropriate cases for those who are reluctant
      with conventional appliances.

PMID- 27029090
TI  - Simultaneous Single Tooth Intrusion and Diastema Closure: A Simplified Approach.
AB  - Re-treatment of relapse with a full bonded appliance following an extensive
      course of fixed mechanotherapy is psychologically unacceptable and time-consuming
      for the patient. This article presents a simple removable appliance, which
      intrudes an extruded maxillary incisor with simultaneous closure of a diastema in
      an effective and fast way, reducing the need for re-treatment with fixed
      mechanotherapy.

PMID- 27029091
TI  - Tongue Size and Posterior Airway Space Changes in Class III Malocclusion After
      Maxillomandibular Surgery: A Retrospective Study.
AB  - The purpose of this study was to evaluate the changes in the airway space after
      surgical correction of Class III skeletal dentofacial deformity and to determine
      if orthognathic surgery alters the airway space and improves obstructive sleep
      apnea. Twenty-four Class III adults treated with orthognathic surgery were
      divided into two groups as Mandibular set-back (Bilateral Sagittal Split
      Osteotomy-BSSO, 10 patients) and two jaw surgery (Bilateral Sagittal Split
      Osteotomy combined with Le Fort I maxillary advancement, 14 patients). Lateral
      cephalometric radiographs were traced before (T0) and 6 months after surgery
      (T1). Steiner and McNamara analysis, linear pharyngeal airway measurements (PNS
      PPW1, SPT-PPW2, E-PPW3, PNS-SPT), tongue volume measurements (TH, Tt-Eb) and
      pharyngeal area measurements (nasopharyngeal, upper oropharyngeal, lower
      oropharyngeal, epiglottis area) were performed. The data obtained was analyzed
      statistically by repeated measurement ANOVA and Duncan's test. The increase of
      PNS-PPW1 was important in two jaw surgery group (p < 0.05). The nasopharyngeal
      area was statistically different between T0 and T1 (p < 0.01), and the lower
      oropharyngeal area was statistically significant between BSSO and two jaw surgery
      groups (p < 0.05). Surgical correction of Class III skeletal dentofacial
      deformity alters posterior airway dimensions. Two jaw surgery is advantageous
      considering the risk for obstructive sleep apnea, because it evokes an increase
      in the upper pharyngeal airway dimensions. Keywords: Tongue size, posterior
      airway space, maxillomandibular surgery.

PMID- 27029092
TI  - An Interdisciplinary Approach in Rehabilitation of an Adult Mutilated Dentition
      with Multiple Missing Permanent Teeth--A Case Report.
AB  - Adult orthodontics has been an area of increasing focus in recent times.
      Comprehensive treatment of adults is more challenging due to a myriad of problems
      that coexist in an adult that makes treatment planning more challenging. A large
      number of individuals seek dental care because of aesthetic reasons, that is, the
      desire to look more attractive by improving their smiles. The role an attractive
      smile plays on a person's self-image and confidence cannot be overemphasized.
      Evaluating and treating patients for the purpose of smile design often involves a
      multi-discipline approach. Achieving an ideal smile may require orthodontics,
      orthognathic surgery, periodontal therapy, including soft tissue repositioning
      and bone re-contouring, cosmetic dentistry, and plastic surgery. This aesthetic
      approach to patient care produces the best dental and dental-facial beauty. This
      paper describes a case report in which an orthodontist, an endodontist, and a
      prosthodontist worked as a team to improve the patients smile and confidence.

PMID- 27029093
TI  - Periodontal Side Effect During Orthopedic Face Mask Therapy.
AB  - A 7-year-old patient exhibited gingival recession of tooth #41 and severe plaque
      accumulation after 3 months of face mask therapy. The recession improved only
      slightly after appropriate oral hygiene instructions and motivation. Decisive
      improvement began when the vertical chin pad extension was reduced to avoid
      pressure on the affected area.

PMID- 27029094
TI  - The "Floss-Ligature" Ligation Technique.
AB  - This clinical pearl describes an alternative technique to aid effective ligation
      of rotated teeth during the aligning stage of fixed appliance treatment. This
      technique has the potential to improve patient experience and confidence, by
      reducing the risk of trauma and discomfort and treatment efficiency, by ensuring
      complete ligation of even severely rotated teeth.

PMID- 27029095
TI  - Orthodontic Camouflage Treatment of Class II Division I Malocclusion in a Patient
      with Myotonic Dystropy.
AB  - Case report of a patient with Class II division I malocclusion, increased overjet
      and reduced overbite treated with combination of functional and fixed appliance
      is presented. Medically she suffered from myotonic dystrophy. Rationale for the
      treatment plan and effect of myotonic dystrophy on treatment outcome are
      discussed.

PMID- 27029096
TI  - Mini-Screw Supported Intrusion Mechanics Used For Open Bite Closure and Facial
      Improvement: A Case Report.
AB  - Open-bite is one of the most challenging malocclusions to be corrected
      orthodontically. Temporary anchorage devices had enabled orthodontists to treat
      open-bite cases successfully. In this case report a 15 years old girl with open
      bite was treated with maxillary molar intrusion with the aid of alveolar mini
      screws.

PMID- 27029097
TI  - Quick and Easy Placement of Coil Spring.
AB  - A tooth displaced palatally in an arch often demands placement of an open coil
      spring for gaining space. Ligation of an archwire with compressed coil spring is
      a cumbersome process. We have made use of 0.010 supreme AJ Wilcock sectional wire
      to compress the open coil spring and place it on the required dental arch.

PMID- 27029098
TI  - Surgical Facilitated Orthodontics for the Correction of an Over Erupted Upper
      First Molar.
AB  - The loss of one or several teeth is a common finding in adult patients. Over
      erupted molars due to the loss of the antagonist, the lack of space, or the
      unwanted inclination of the adjacent teeth are real complications specific to
      dental implant prosthetic rehabilitation A patient with an over erupted upper
      left first molar was treated with surgical-facilitated orthodontics.

PMID- 27029099
TI  - Orthodontic Treatment in Adult Patient with Reduced Periodontium: A Case Report.
AB  - Patients presenting reduced periodontium represent a major concern for
      orthodontists. The purpose of this article is to present the clinical case of an
      adult patient who presented sequel of periodontal disease (diastemas)
      compromising her dental aesthetics. She was subjected to an orthodontic treatment
      with the application of light forces distant from the teeth with reduced
      periodontium. A periodontal support therapy was successfully implemented. The
      final stage of the treatment indicated satisfactory occlusal and periodontal
      characteristics.

PMID- 27029100
TI  - Kansal Separator As an Effective Fixed Retainer Stabilizer.
AB  - Fixed bonded retainers are increasingly being recommended as the only way to
      ensure long-term stability of an orthodontic treatment result. However, frequent
      debonding of the fixed bonded retainer is a constant source of frustration for
      the orthodontist. Bond failure is most commonly attributed to the difficulty
      encountered in stabilizing the retainer wire in the precise position during the
      bonding process. This paper presents a clinical approach that makes use of Kansal
      Separator; a self-secured orthodontic spring separator as a simple, efficient,
      and dependable fixed retainer stabilizer.

PMID- 27029101
TI  - Cephalometric Superimposition.

PMID- 27029102
TI  - There Is Time for Calculation in Speed Chess, and Calculation Accuracy Increases
      With Expertise.
AB  - The recognition-action theory of chess skill holds that expertise in chess is due
      primarily to the ability to recognize familiar patterns of pieces. Despite its
      widespread acclaim, empirical evidence for this theory is indirect. One source of
      indirect evidence is that there is a high correlation between speed chess and
      standard chess. Assuming that there is little or no time for calculation in speed
      chess, this high correlation implies that calculation is not the primary factor
      in standard chess. Two studies were conducted analyzing 100 games of speed chess.
      In Study 1, we examined the distributions of move times, and the key finding was
      that players often spent considerable time on a few moves. Moreover, stronger
      players were more likely than weaker players to do so. Study 2 examined skill
      differences in calculation by examining poor moves. The stronger players made
      proportionally fewer blunders (moves that a 2-ply search would have revealed to
      be errors). Overall, the poor moves made by the weaker players would have
      required a less extensive search to be revealed as poor moves than the poor moves
      made by the stronger players. Apparently, the stronger players are searching
      deeper and more accurately. These results are difficult to reconcile with the
      view that speed chess does not allow players time to calculate extensively and
      call into question the assertion that the high correlation between speed chess
      and standard chess supports recognition-action theory.

PMID- 27029103
TI  - Does Number of Perceptions or Cross-Modal Auditory Cueing Influence Audiovisual
      Processing Speed?
AB  - What factors contribute to redundant target processing speed besides statistical
      facilitation? One possibility is that multiple percepts may drive these effects.
      Another, although not mutually exclusive hypothesis, is that cross-channel cueing
      from one modality to another may influence response times. We implemented an
      auditory-visual detection task using the sound-induced flash illusion to examine
      whether one or both of these possibilities contributes to changes in processing
      speed; we did so by examining the data of individual participants. Our results
      indicated shorter response times in several participants when multiple flashes
      were perceived in the standard sound-induced flash illusion, thereby replicating
      previous work in the literature. Additionally, we found evidence for faster
      responses in several participants when carrying out the same analysis in trials
      in which 1 beep was presented with 2 real flashes. Overall, our analysis
      indicates that some observers benefit from cross-modal facilitation, whereas
      others may benefit from a combination of cross-modal facilitation and increased
      perceptual judgments.

PMID- 27029104
TI  - The Face Inversion Effect: Roles of First- and Second-Order Configural
      Information.
AB  - The face inversion effect (FIE) is a reduction in recognition performance for
      inverted faces compared with upright faces. Several studies have proposed that a
      type of configural information, called second-order relational information,
      becomes more important with increasing expertise and gives rise to the FIE.
      However, recently it has been demonstrated that it is possible to obtain an FIE
      with facial features presented in isolation, showing that configural information
      is not necessary for this effect to occur. In this article we test whether there
      is a role for configural information in producing the FIE and whether second- or
      first-order relational information is particularly important. In Experiment 1, we
      investigated the role of configural information and local feature orientation by
      using a new type of "Thatcherizing" transformation on our set of faces, aiming to
      disrupt second-order and local feature orientation information but keeping all
      first-order properties unaltered. The results showed a significant reduction in
      the FIE for these "new" Thatcherized faces, but it did not entirely disappear.
      Experiment 2 confirmed the FIE for new Thatcherized faces, and Experiment 3
      establishes that both local feature orientation and first-order relational
      information have a role in determining the FIE.

PMID- 27029105
TI  - Word Frequency Effects for LEET Lettering in Word Recognition.
AB  - Letter substitution has been shown to have a cost to word recognition
      performance, such as increased reaction time. The use of orthographically similar
      numbers or symbols as a substitute for letters is known as LEET. Perea,
      Dunabeitia, and Carreiras (2008) showed that word recognition was not affected
      when LEET substitutions were used as primes. This study examined whether the
      effects of LEET prime substitutions would remain constant across word frequency.
      The apparent lack of substitution costs may have been an effect of word-level
      processing such as holistic bias for high-frequency words. Evidence that LEET
      does not have an appreciable cost to performance across word frequency suggests
      that such orthographic substitutions are processed much like normally lettered
      words, which supported Perea et al.'s findings. It was suggested that LEET
      substitutions offset substitution costs because of orthography (because of more
      complete processing of nonsubstituted letters) rather than lexical effects (i.e.,
      holistic bias).

PMID- 27029106
TI  - Familiarity and Aptness in Metaphor Comprehension.
AB  - The career of metaphor hypothesis suggests that novel metaphors are understood
      through a search for shared features between the topic and vehicle, but with
      repeated exposure, the figurative meaning is understood directly as a new
      category is established. The categorization hypothesis argues that instead good
      or apt metaphors are understood through a categorization process, whether or not
      they are familiar. Only poor metaphors ever invoke a literal comparison. In
      Experiment 1, with aptness equated, we found that high familiarity speeded
      comprehension time over low-familiarity metaphors. In Experiment 2a, providing a
      literal prime failed to facilitate interpretation of low-familiarity metaphors,
      contrary to the career of metaphor hypothesis. In Experiment 2b, with familiarity
      equated, high- and low-aptness metaphors did not differ, contrary to the
      categorization hypothesis.

PMID- 27029107
TI  - Psychodynamic Emotional Regulation in View of Wolpe's Desensitization Model.
AB  - The current research belongs to the stream of theoretical integration and
      establishes a theoretical platform for integrative psychotherapy in anxiety
      disorders. Qualitative metasynthesis procedures were applied to 40 peer-reviewed
      psychoanalytic articles involving emotional regulation. The concept of
      psychodynamic emotional regulation was found to be connected with the categories
      of desensitization, gradual exposure, containment, and transference. This article
      presents a model according to which psychoanalytic psychotherapy allows anxiety
      to be tolerated while following the core principles of systematic
      desensitization. It is shown that despite the antiresearch image of
      psychoanalytic psychotherapy, its foundations obey evidence-based principles. The
      findings imply that anxiety tolerance might be a key goal in which the cumulative
      wisdom of the different therapies can be used to optimize psychotherapy outcomes.

PMID- 27029108
TI  - Self-Objectification and the Use of Body Image Coping Strategies: The Role of
      Shame in Highly Physically Active Women.
AB  - We investigated the mediating role of body shame in the relationship between self
      objectification and body image coping strategies in highly physically active
      university women. Bivariate correlations revealed body shame was positively
      related to self-objectification, appearance fixing, and avoidance coping but
      unrelated to positive rational acceptance. In addition, self-objectification was
      positively related to appearance fixing and avoidance coping but unrelated to
      positive rational acceptance. Mediation analyses showed that body shame partially
      mediated the relationship between self-objectification and avoidance and
      appearance fixing coping but did not mediate the relationship between self
      objectification and positive rational acceptance. Future research should examine
      other potential mediators or moderators in this relationship and explore the role
      of positive body image framed within self-objectification theory.

PMID- 27029109
TI  - [TYPING OF VIBRIO CHOLERAE NON O1/NON O139 STRAINS, ISOLATED IN ROSTOV REGION IN
      2014].
AB  - AIM: Comparative study of antibiotics resistance and VNTR-typing of Vibrio
      cholerae non O1/ non O139 strains, isolated on the territory of Rostov region in
      2014. MATERIALS AND METHODS: Antibioticogramms of strains were determined by
      serial dilution method in dense nutrient medium according to MG 4.2.2495-09
      (2009). Pheno-, sero- and VNTR-typing was carried out by conventional-methods.
      RESULTS: The studied strains belonged to V. cholerae species, did not agglutinate
      with O1 and O139 sera, were atoxigenic hemolysis-positive, did not contain genes
      of cholera toxin and toxin-coregulating pili of adhesion, contained genes of
      hemagglutinin/protease, protease PrtV, collagenase, cytotonic factor Cef, outer
      membrane protein-OmpW, tol- and -vps-clusters, regulatory genes toxR and hapR.
      Antibioticogramms of the strains have shown the presence of cultures, resistant
      to ampicillin, ceftazidime-furazolidone, trimethoprim/sulfamethoxazole with
      intermediate resistance to streptomycin, kanamycin, gentamycin, amikacin,
      netilmicin, Approximately 20% of isolates had multiple drug resistance. Data of
      VNTR- and genotyping confirmed a possibility of water transmission route of the
      infection. CONCLUSION: Execution of monitoring of cultures from environmental
      samples is necessary for timely detection of genetic characteristics, antibiotics
      resistance.

PMID- 27029110
TI  - [EPIDEMIOLOGIC MANIFESTATIONS OF VIRAL HEPATITIS C IN REPRESENTATIVES OF
      CAUCASIAN AND MONGOLOID RACES].
AB  - AIM: Present comparative epidemiologic characteristics of viral hepatitis C in
      Mongolia and Irkutsk Region taking into account racial origin of the studied
      populations. MATERIALS AND METHODS: The studies were carried out in 2009-014 on
      the territory of Irkutsk Region in Mongolia. Prevalence of viral hepatitis based
      on serological monitoring, virus RNA detection, risk factors, change in structure
      of circulating genotypes, hepatocellular carcinoma morbidity were studied.
      RESULTS: Epidemiologic manifestations of viral hepatitis C in Mongolia, in
      contrast to Irkutsk Region, are characterized by, a wider prevalence of the
      disease, predominance of the fraction of seropositive individuals in age category
      of above 50 years and predominance of genotype 1 virus in circulation. In recent
      years an evolution of diversity of circulating' irus genotypes, ook place towards
      a reduction of the fraction of genotype in Mongolia and Russia due tor ni ncrease
      of the fraction of genotype-3. Expressed,differences in average-annual values of
      hepatocellular carcinoma morbidity were detected, that were more than 10 times
      higher among Mongoloids compared with Caucasians. CONCLUSION: Pronounced
      differences were detected in manifestations of epidemic process of viral
      hepatitis C in Mongolia and Asian part of Russia, represented by Eastern Siberia,
      that are associated with ethnic, social and, cultural living conditions of the
      indigenous population.

PMID- 27029111
TI  - [SOME FEATURES OF MANIFESTATIONS OF EPIDEMIC PROCESS DURING ACUTE INTESTINAL
      INFECTIONS IN MOSCOW].
AB  - AIM: Study manifestations of epidemic process during acute intestinal infections
      to establish reasons of low effectiveness of the prophylactic measures carried
      out and evaluation of the role of rotavirus infection in general disease
      structure of intestinal infections of unknown etiology. MATERIALS AND METHODS:
      Data on morbidity of acute intestinal infections of population of Moscow were
      analyzed. Hospitalized patients with acute intestinal infections were examined
      using real-time PCR method test-systems of laboratory of molecular virology of
      Mechnikov RIVS with subsequent typing. RESULTS: Evaluation of multi-year
      manifestations of epidemic process of morbidity of acute intestinal infections in
      Moscow has shown, that the cumulative morbidity does not have a tendency of
      reduction, because the proportion of infections with undeciphered etiological
      factors is almost 80% of the total aggregate morbidity. The proportion of
      rotavirus infection in total morbidity of AII of established etiology increased
      from 53.2 in 2004 to 82.6% in 2014. Morbidity in childrenwith rotavirus infection
      is 6 times higher than morbidity in adults. CONCLUSION: The results obtained give
      evidence on the necessity of carrying out specific prophylaxis against viral
      intestine infection, mostly of rotavirus and norovirus infections. The highest
      effect should have been expected from use of a bi-vaccine, development of which
      seems quite an actual problem.

PMID- 27029112
TI  - [ROLE OF VARIOUS ANTIGENIC PREPARATIONS OF FRANCISELLA TULARENSIS IN FORMATION OF
      ALLERGY REACTION IN HUMANS AND ANIMALS].
AB  - AIM: Study the role of LPS in induction of anti-tularemia immunity in humans and
      animals. MATERIALS AND METHODS: Activity of various antigenic preparations of
      tularemia microbe, including highly purified from protein and S- and R-LPS, was
      studied using leukocytolysis reaction with blood of vaccinated humans and guinea
      pigs and skin allergy test (guinea pigs). RESULTS: Only the whole cells of
      Francisella tularensis, killed in protein non-denaturating conditions and
      conserving full S-LPS structure (tularin+) were shown to be inductors of delayed
      type hypersensitivity reaction. Alterations in LPS structure (tularin-) results
      in a significant decrease, and denaturation of bacterial proteins (during
      boiling) results in a complete loss of immune stimulating properties of the
      preparations. Purified LPS preparations and O-polysaccharide fraction of S-LPS
      are not able to activate cell-mediated immunity. CONCLUSION: The presence of LPS
      with the full structure affects the ability of antigenic preparations of F.
      tularensis to cause allergic reactions, and thus, form cell-mediated
      antitularemia immunity. LPS of F. tularensis can not be excluded as an adjuvant
      and provides the most effective presentation of epitopes of protein molecules for
      interaction with receptors of T-lymphocytes.

PMID- 27029113
TI  - [FEATURES OF MASS-SPECTROMETRIC PROTEIN PROFILES OF STRAINS OF BRUCELLOSIS
      CAUSATIVE AGENT DURING PREPARATION OF CULTURE ON VARIOUS NUTRIENT MEDIA].
AB  - AIM: Carry out comparative analysis using time-of-flight mass-spectrometry with
      matrix laser desorption/ionization (MALDI-TOF MS) of protein profiles of
      brucellosis causative agents (Brucella melitensis Rev-1 and Brucella abortus
      19BA), cultivated in various nutrient media: Albimi agar, brucellagar and
      erythrit-agar. MATERIALS AND METHODS: Vaccine,strains: Brucella melitensis Rev-1
      and Brucella abortus 19BA. Protein profiling in linear mode on Microflex "Bruker
      Daltonics" MALDI-TOF mass-spectrometer. RESULTS: A number of characteristic
      features of brucella mass-spectra was detected: in particular, preservation of
      the total qualitative composition of protein profiles of cultures and significant
      differences in the intensity of separate peaks depending on the nutrient medium
      used. CONCLUSION: Based on the analysis of the data obtained, use of Albimi agar
      as the nutrient medium for preparation of brucella culture samples for mass
      spectrometric analysis was shown to be optimal.

PMID- 27029114
TI  - [TYPING OF LEPTOSPIRA SPP. STRAINS BASED ON 16S rRNA].
AB  - AIM: Comparative typing of Leptospira spp. strain collection based on analysis of
      16S RNA fragment. MATERIALS AND METHODS: 2 pairs of primers were used for PCR,
      that jointly flank 1423b.p. sized fragment. Sequences of Leptospira spp. strain
      16S rRNA, presented in the international database, were used for phylogenetic
      analysis. RESULTS: A high similarity, including interspecies, of the 16S fragment
      in Leptospira spp. strains was shown independently of the source, serovar and
      serogroup. Heterogeneity of the primary matrix, spontaneous mutations of hotspots
      and erroneous nucleotide couplings, characteristic for 16S sequence of pathogenic
      Leptospira spp. strains, are discussed. Molecular-genetic characteristic of
      certain reference Leptospira spp. strains by 16S sequence is obtained.
      CONCLUSION: Results of the studies give evidence on expedience of introduction
      into clinical practice of identification of Leptospira spp. by 16S sequence
      directly from the clinical material, that would allow to significantly reduce
      identification time, dismiss complex type-specific sera and other labor-intensive
      methods.

PMID- 27029115
TI  - [SPECTRUM OF ANTIBIOTIC RESISTANCE AND PREVALENCE OF OXA-CARBAPENEMASES AMONG
      ACINETOBACTER BAUMANNII STRAINS, ISOLATED FROM PATIENTS OF SURGICAL AND
      REANIMATION DEPARTMENTS IN MOSCOW].
AB  - AIM: Characterize spectrum of antibiotics resistance of Acinetobacter baumannii
      strains, isolated from patients of 8 surgical and reanimation departments of 3
      medical institution of Moscow, and determine molecular-genetic mechanisms of
      stability of their carbapenem-resistant forms. MATERIALS AND METHODS: 95 strains
      of A. baumannii, isolated from patients of reanimation and surgical departments
      of Moscow in 2012-2014, were studied. Sensitivity of strains to antibiotics was
      tested phenotypically according to recommendations of EUCAST. The presence of
      VIM, IMP, OXA-23, OXA-40, OXA-48, OXA-58 and NDM genes in the studied strains was
      determined by polymerase chain reaction in real time. RESULTS: 86.3% of strains
      turnedout to be non-sensitive to carbapenems, sensitive--13.7%. 80.0% of strains
      were non-sensitive to gentamicin, 80.0% of strains--to netilmicin, 94.7% of
      strains--to ciprofloxacin 2.1%--to colistin. 91.6% of isolates have shown non
      sensitivity to members of 2 and more classes of antibiotics, 78.9% of strains--to
      members of 3 classes. 2 strains were panresistant, 4.2% (4/95) of the isolates
      were sensitive to all the classes of antibiotics. Metallo-beta-lactamases were
      not detected. Genes of carbapenemases (OXA-23 and/or OXA-40) were detected in
      85.3% (81/95) of strains, characterized phenotypically as non-sensitive to
      carbapenems. CONCLUSION: The results obtained shown an increase of resistance to
      carbapenems and multiple resistance in clinically significant strains of A.
      baumannii. Resistance to carbapenems is associated with OXA-23 and OXA-40 genes.
      The conclusions allow to justify perspectives of introduction of technologies of
      molecular-genetic testing of antibiotics resistance.

PMID- 27029117
TI  - [MASS-SPECTROMETRY IN MICROBIOLOGICAL PRACTICE OF SCIENTIFIC CENTRE OF
      OBSTETRICS, GYNECOLOGY AND PERINATOLOGY].
AB  - AIM: Comparative evaluation of species identification of microorganisms by MALDI
      TOF mass-spectrometry and automatic biochemical analyzer VITEK2 Compact 30.
      MATERIALS AND METHODS: Species identification of 18,400 isolates of
      microorganisms (staphylococci, streptococci, enterococci, enterobacteria,
      nonfermenting gram-negative bacteria, lactobacilli, anaerobes, yeast fungi,
      neisseriae), isolated from vagina of pregnant and non-pregnant women and from
      newborns, was carried out. Identification of the isolated microorganisms was
      carried out by automatic bacteriologic analyzer VITEK2 Compact30 (BioMerieuX,
      France) and MALDI-TOF-MS analysis method on AutofleXIII (Bruker Daltonics,
      Germany) mass-spectrometer. RESULTS: Comparative identification of 2005 isolates
      of microorganisms was carried out. Sequencing of ribosomal RNA was used as a
      reference method. Authenticity of species identification my MALDI-TOF-MS analysis
      method was: for staphylococci (95.8%), enterococci (97.5%), enterobacteria
      (98.4%), nonfermenting gram-negative bacteria (93.6%), beta-hemolytiC
      staphylococci (93.8%), lactobacilli (92.8%), yeast fungi (99.9%). CONCLUSION:
      Introduction of MALDI-TOF-MS analysis technology into practical work of
      microbiological laboratories exceeds previously used methods of microbiological
      testing in terms of speed; cost and authenticity of identification of a wide
      spectrum of microorganisms.

PMID- 27029116
TI  - [SAFETY AND IMMUNOGENICITY OF A NATIONAL COMBINED VACCINE AGAINST PERTUSSIS,
      DIPHTHERIA, TETANUS, HEPATITIS B AND Hib-INFECTION, CONTAINING ACELLULAR
      PERTUSSIS COMPONENT, DURING IMMUNIZATION OF ADULTS].
AB  - AIM: Study safety, reactogenicity and immunologic effectiveness of a national
      combined vaccine against diphtheria, pertussis (acellular component), tetanus,
      hepatitis B and Hib-infection during immunization of volunteers aged 18-60 years.
      MATERIALS AND METHODS: The study was carried out in accordance with ethical
      standards and requirements, regulated by Helsinki declaration and Good clinical
      practice (ICHGCP). In a simple non-randomized clinical trial 20 adult volunteers
      took part, the mean age of those was 46.9 years. RESULTS: Registered: post
      vaccination reactions (both local and systemic) were mild and of moderate degree
      of severity, stopped independently after 2-3 days without administration of drug
      treatment. Postvaccinal complications were not noted. Parameters of general and
      biochemical analysis of blood, urine, IgE content in dynamics of immunization
      were within normal limits. A single administration of aAPDT--HepB+Hib to
      individuals aged 18-60 years resulted in development of antibodies against all
      the components of the preparation. Seroconversion factor fluctuated from 6.9 to
      53.5: CONCLUSION: The results obtained allow to recommend the vaccine for
      evaluation of its safety, reactogenicity, immunologic and prophylaxis
      effectiveness in randomized clinical observation trials in children.

PMID- 27029118
TI  - [EVALUATION AND PROGNOSIS OF EPIDEMIOLOGIC SITUATION FOR LYME BORRELIOSIS IN
      VLADIMIR REGION].
AB  - AIM: Evaluation and prognosis of epidemiologic process for Lyme borreliosis (Lb)
      in Vladimir region. MATERIALS AND METHODS: Report form No. 2 "Data on infectious
      and parasitic diseases". Territorial differentiation of morbidity was carried out
      in ArcView 3.1 program. The following climate parameters were used: average
      monthly air temperature, number of days of the month with precipitation, air
      humidity, atmospheric pressure, size of snow cover and content of oxygen in air
      in every month for the period of 2004-2012. Statistical treatment, correlation
      regression analysis was carried out in Statistica program. RESULTS: 1211 cases of
      Lb morbidity were registered for the period of 2005-2012 in Vladimir region, that
      had increased by 46%. A territorial differentiation of the disease is noted.
      Average monthly temperature of July and September of the preceding year were
      established to be the most significant parameters, that affect the epidemiologic
      process. A mathematical model, that can be used for prognosis of epidemiologic
      situation for Lb, was constructed. CONCLUSION: The mathematical model shows, that
      increased values of morbidity can be expected, if July of the preceding year was
      fairly warm, and September, on the contrary, differed by reduced values of air
      temperature.

PMID- 27029119
TI  - [STUDY OF COMPOSITION OF PLANT EXTRACTS, POSSESSING ANTIMICROBIAL EFFECT AGAINST
      VIBRIO CHOLERAE EL TOR, USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY].
AB  - AIM: Study the composition of plant extracts using high-performance liquid
      chromatography. (HPLC) and evaluation of their antimicrobial effect against
      Vibrio cholerae El Tor. MATERIALS AND METHODS: Qualitative and quantitative
      composition of plant extracts was studied using HPLC. Determination of
      sensitivity of microorganisms to plant extracts was carried out by diffusion into
      agar method and serial dilutions method. RESULTS: Antibacterial effect of water,
      water-alcohol and acetone extracts of roots of Limonium gmelinii L., Berberis
      vulgaris L. and Glycyrrhiza glabra L. was studied. The most effective methods of
      extraction of biologically active substances, possessing antimicrobial effect
      against various strains of V. cholerae El Tor, were determined. CONCLUSION: The
      use of HPLC allowed to establish the presence of catechines, alkaloids
      protoberberines and glycyrrhizic acid in xtracts, possessing antimicrobial effect
      against V. cholera El Tor strains.

PMID- 27029120
TI  - [ASSOCIATION OF POLYMORPHIC MARKERS IN GENES OF INNATE IMMUNITY IN PATIENTS WITH
      PERIODONTITIS AND INFLAMMATORY DISEASES OF UPPER RESPIRATORY TRACT].
AB  - AIM: Search of association of polymorphisms in DEFB1, IL-10, TNF-alpha and TLR2
      genes with development of chronic generalized periodontitis in representatives of
      Ural region (Caucasian race). MATERIALS AND METHODS: 142 patients, that were
      split into 3 groups, took part in the study: a group of patients with
      periodontitis, a group with frequent inflammatory disease of upper respiratory
      tract and a comparison group--healthy donors. A study of polymorphic markers was
      carried out: DEFB1 (-44G/C), DEFB1 (-20A/G), IL-10 (-1082.A/G), TNF-alpha (-308
      G/A), Arg753Gln and Arg677Trp using PCR in real time mode. RESULTS: Association
      of infectious pathology ofupper respiratory tract and development of
      periodontitis diseases with markers in DEFB1 (-44G/C) and Arg753Gln and Arg677Trp
      genes was determined. Significant differences in distribution of genotypes and
      alleles of genes IL-10 and TNF-alpha in the group of patients with periodontitis
      and comparison group were not detected. CONCLUSION: DEFB1 (-44G/C) polymorphism
      can be examined as a marker of periodontitis development risk.

PMID- 27029121
TI  - [PAPILLOMAVIRUS INFECTION: PRINCIPLE CHARACTERISTICS, CLINICAL MANIFESTATIONS,
      VACCINE PROPHYLAXIS].
AB  - Papillomaviruses are a large and diverse group of viruses. It includes
      approximately 200 fully described types that have been detected in humans. Human
      papilloma viruses (HPV) are etiologic agents during various, benign and malignant
      lesions of mucous membrane and skin epithelium. Very importantly, persistent HPV
      infection of certain types is a leading cause of carcinoma of uterine cervix,
      penis, vulva; vagina, anal canal and fauces (including tongue base and tonsils).
      HPV infection prophylaxis is the best means to control HPV-conditioned diseases,
      and vaccination, as had been demonstrated, --the most effective method of its
      prophylaxis. In this paper principle characteristics and clinical manifestations
      of papillomavirus infection, as well as effectiveness of vaccination against HPV
      are examined.

PMID- 27029122
TI  - [PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON
      OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS].
AB  - Live genetic engineering anthrax vaccines on the platform of avirulent and
      probiotic micro-organisms are a safe and adequate alternative to preparations
      based on attenuated Bacillus anthracis strains. Mucosal application results in a
      direct contact of the vaccine preparations with mucous membranes in those organs
      arid tissues of the macro-organisms, that are exposed to the pathogen in the
      first place, resulting in a development of local and systemic immune response.
      Live recombinant anthrax vaccines could be used both separately as well as in a
      prime-boost immunization scheme. The review focuses on immunogenic and protective
      properties of experimental live genetic engineering prearations, created based on
      members of geni of Salmonella, Lactobacillus and adenoviruses.

PMID- 27029123
TI  - [ACTUAL PROBLEMS OF EPIDEMIOLOGIC CONTROL, LABORATORY DIAGNOSTICS AND PROPHYLAXIS
      OF CHOLERA IN RUSSIAN FEDERATION].
AB  - Main problems of system of epidemiologic control for cholera active in Russian
      Federation, as well as laboratory diagnostics and vaccine prophylaxis of this
      especially dangerous infection, that had emerged in the contemporary period of
      the ongoing 7th pandemic of cholera, are discussed. Features of the genome of
      natural strains of Vibrio cholerae of El Tor biovar, that possess a poten- tial
      epidemic threat, as well as problems, that have emerged during isolation of these
      strains from samples of water of surface water bodies during their monitoring,
      are also examined. The main direction of enhancement of the system of
      epidemiologic control for cholera consist in develop- ment of a new algorithm of
      differentiation of administrative territories of Russian Federation by types of
      epidemic manifestations, as well as optimization of monitoring of environment
      objects. Integration of modern highly informative technologies into practice, as
      well as development of new generation diagnostic preparations based on DNA-chips
      and immunechips is necessary to increase effectiveness of the conducted operative
      and retrospective diagnostics in the contemporary period. Creation of national
      cholera vaccine, ensuring simultaneous protection from cholera causative agents
      of both O1 and O139 serogroups, is also required.

PMID- 27029124
TI  - [VIRAL HEPATITIS C: EVOLUTION OF THE EPIDEMIOLOGIC PROCESS, EVOLUTION OF THE
      VIRUS].
AB  - Periodization of the evolution of epidemic process of hepatitis C is given based
      on the results of phylodynamic, phylogeographic, historic and demographic
      studies: invasion of the virus into European and North-American population in
      1700-1850; primary activation of the epidemic process in the years of the World
      War 1; expansive giowth of prevalence in 40--60s of the 20th century due to mass
      parenteral interventions; new rise due to heroine drug abuse in 60--80s of the
      20th century; manifold reduction of incidence of acute hepatitis C in industrial
      countries for the last 10-15 years as a result of general medical measures of
      prevention of hemocontact infec-tions. A problem of possibility of hepatitis C
      management and necessity of evaluation of effectiveness of existing prophylaxis
      measures involving quantitative analytical methods of epidemiology is discussed.
      Data from phylogenetic studies on stages of hepatitis C virus evolution (HCV) are
      provided: division of its root genetic lineage with homologous hepaciviruses of
      animals 985--2013 years ago; division of HCV into genotypes 500--2000 years ago;
      division of genotypes into subtypes 70--300 years ago. Contribution of mutations
      and genetic recombinations into HCV evolution is discussed. Genotyping is stated
      as an inefficient approach for determination of pathogenicity determinants,
      immune evasion, non-responsiveness to therapy, as well as search for predictors
      of infection outcome. A necessity of genomic approach for these aims is
      justified, as well as for risk monitoring, ensuing from continuing evolution and
      biodiversity of HCV and other hepaciviruses.

PMID- 27029125
TI  - [A change to the traditional medicine in Persia?].
AB  - Until the 19th century, medicine in Persia is mainly based on the humoral theory.
      According to some authors, the introduction of anatomical pathology principles is
      due to the particular political and health circumstances of this century and the
      intellectual evolution of Persian physicians. By making a comparison between the
      text of Shirazi, the prominent Persian physician of the 19th century, and the
      writings of Avicenna on cholera and heyze (acute diarrhea), this article tests
      this hypothesis.

PMID- 27029126
TI  - [Emile Esperandieu and the stamps of Roman ophthalmologists].
AB  - Major Emile Esperandieu, the famous author of the Recueil des bas-reliefs de la
      Gaule, also compiled the Recueil des cachets d'oculistes romains, a very useful
      corpus for the history of ancient ophtalmology. He was a striking example of the
      social and intellectual situation of a scholar out of the University, and of the
      morbid emulation between French scholarship and that of other European countries
      in the field of ancient epigraphy.

PMID- 27029127
TI  - [The Father of sign language].
AB  - During the 19th century, doctors confronted with deafness (among whom Itard)
      played an essential part in the understanding of the diseases of the ears and the
      education of deaf mutes. Then in the 20th century the use of cochlear implants
      was a great leap forward, but a great problem too, deaf mutes not considering
      themselves as patients or disabled persons.

PMID- 27029128
TI  - [Short introduction to the history of otorhinolaryngology and craniofacial
      surgery].
AB  - OHNS is a medical specialty born at the end of the 19th century. It is the
      congruence of otology and laryngology, rapidly associated with rhinology. It went
      through three chronological steps: construction in the second part of the 19th
      century, consolidation in the first part of 20th century and extension in the
      second part of the 20th and beginning of the 21st century. Scientifically, OHNS
      was set out into five partially layered phases: bedside teaching, introduction of
      anatomopathology, invention of clinic experiments, expansion of surgery, and use
      of highly technological advances. The increase of knowledge became progressively
      exponential due to concomitant progress. It lead to a renewal of the subdivision
      of the specialty into otology, rhinology, laryngology, head and neck surgery,
      pediatric OHNS, otoneurology, facioplastic surgery, and phoniatry in the last
      decades of the 20th century.

PMID- 27029129
TI  - [Paleopathology of deafness: skulls of the Dupuytren Museum].
AB  - In the 18th and 19th centuries, the Dupuytren Museum was indispensable for the
      knowledge of pathological anatomy for physicians and surgeons. Nowadays, it is
      more a museum than a learning unit, but it provides an opportunity to understand
      through numerous scientific studies the origin of diseases, injuries mechanism
      and the functional consequences of which could suffer some patients. This study
      illustrates the interest of the study on pieces in pathological anatomy's
      museums, this time across selected skulls which belonged to hearing loss people.
      bizarre.

PMID- 27029130
TI  - [History of a letter addressed to the Academy of Medicine of Paris].
AB  - The author presents an autograph manuscript sent from Laval by Dr Hubert to Paris
      Academy of medicine in which he reports the birth of a freak who died at birth
      during a difficult delivery. This freak is, according to our contemporary
      classifications, a thoraco pagus who represents from 70 to 73% of symmetrical
      conjoined monmphalic twins. The address mentioned is that of the first location
      of the Academy. He gives explanations concerning both the Academy and Dr Hubert,
      a Parisian MD who was a regular contributor. He goes on explaining how it was
      received by Professor Adelon, then annual secretary. The letter sets up in the
      margin a commission offamous scientists such as Geoffroy Saint-Hilaire, Serres et
      Antoine Dubois. The case was presented to the Academy during the session of 17
      november 1829. Though the Academy does not seem to have been able to keep
      detailed archives of that period, the Archives Generales de Medecine lets us know
      the reactions.

PMID- 27029131
TI  - [Francois Humbert, an unknown orthopedist, initiator of cures for the "lame"].
AB  - Francois Humbert (1776-1850) created in 1817 the first French orthopaedic
      institution, at a great turning point in orthopedics. Interested in "lame people"
      and "hunchbacks", he treated congenital hip dislocation and scoliosis, for about
      30 years. Humbert's medical practice illustrated very well the deep
      transformation which occured in orthopedics at the beginning of the 19th century.
      As testimonies of Humbert's work, there are the books he published, his Memoirs,
      some buildings of his institution which have been reconverted into houses, but
      above all thirty-eight models of his "machines". In spite of the fact that he was
      the first to consider congenital hip dislocation like a curable disease, his work
      quickly became unknown after his death.

PMID- 27029132
TI  - [The dinner of interns of the Hospital of Paris, 1855].
AB  - Based on a hitherto unpublished notebook this paper describes and analyses the
      "banquet de l'internat" en 1855, the social dinner shared by the "internes" or
      residents, former and present, and their masters, in a famous Parisian
      restaurant. Some thirty year later another "banquet" will be organized for the
      first young women who just became internes.

PMID- 27029133
TI  - [History of trichinellosis in the history of the catalog of the French National
      Library].
AB  - The Open Line public access catalogue of the French National Library was
      consulted for the following key-words: trichine, trichinose, Trichina,
      trichinellose. Around 50 monographs in French were published during three
      periods: 1860-1869, 1880-1889 and 1970-1979. The 1970-1979 wave was linked with
      the emergence in Paris and its region of an outbreak related to horse-meat
      consumption. The 1880-1889 wave is explained by an economical war between Europe
      and the United States of America. The 1860-1870 wave occurred when the parasite
      cycle and the human disease were identified in Germany by Virchow and Zenker. In
      addition, some political and economic events could have increased the fear of the
      disease.

PMID- 27029134
TI  - [The chief surgeon Claude Louis Somme (1772-1855) French military physician,
      surgeon of Antwerp hospital].
AB  - Claude Louis Somme was born in Paris in 1772. After surgical studies between 1790
      and 1792, he successfully embraced a military career in the armies of Napoleon at
      different fronts and in several hospitals. In 1806 he submitted his doctoral
      thesis at the Special Medical School of Strasburg, Dissertation upon Pain. The
      same year he presented his dismissal from he imperial armies and became chief
      surgeon at the St Elisabeth hospital of Antwerp where he stayed on duty until his
      death in 1855. Somme wrote a lot of medical books: surgical, anatomical and
      physiological. After the battle of Waterloo one third of the injured soldiers
      were transferred to Antwerp and were attended in his department. He also played
      an important role as a professor at the Primary Medical School of Antwerp. Somme
      also created the botanical garden of Antwerp, close to the hospital.

PMID- 27029135
TI  - [Family suicide by carbon monoxide poisoning, Paris 1890-1899. Role of popular
      illustrations].
AB  - History has nearly forgotten a series of six suicides by family groups composed
      of parents and children residing in the same household, which received wide
      attention in the 1890s. This period saw the launch of illustrated supplements to
      Parisian daily newspapers, several of which produced dramatic depictions of these
      tragedies. The cause of the suicides was believed to be extreme poverty or the
      fear thereof. In the latter cases, it is argued that newspaper illustrations
      facilitated the carrying out of suicidal acts by persons whose circumstances
      placed them at risk for suicide. The choice of death by carbon monoxide poisoning
      was due to a wish by parents to die together with their children and to the hope
      of a peaceful death.

PMID- 27029136
TI  - [Three female physicians of the Montpellier faculty at the turn of the 19th
      century].
AB  - As a part of a study on the census of female students listed in medicine at the
      faculty of Montpellier since it opened to women in 1868 until the end of the
      Third Republic, we selected three women who passed their thesis respectively in
      1899, 1905 and 1911. Thanks to the documents found in the archives, and the
      testimony of their descendants, we were able to trace their biography. In
      obstetrics, surgery and orthopaedics, they were exceptional pioneers and set an
      example for new vocations.

PMID- 27029137
TI  - [A shoulder operation in 1878 on the Juliette Gide, mother of Andre Gide, by the
      doctors Brouardel and Berger].
AB  - A hitherto unpublished letter, very probably of 6 July 1878, written by Anna
      Shackleton to Claire Demarest, gives a detailed description of an operation
      conducted in Paris the previous day by Drs. Paul Brouhardel and Paul Berger to
      reduce a month-old dislocated shoulder. The shoulder in question is that of
      Juliette Gide, the mother of the famous French writer Andre Gide. Anna Shackleton
      was the Rouen-born English ex-governess of the adolescent Juliette (Claire's
      younger sister) who had become her close friend. The operation takes place in the
      Gide family apartment and involves five other medical staff assisting the two
      supervising doctors, both of whom, Brouardel in particular, were to follow
      brilliant careers. Under chloroform for an hour the patient undergoes distraction
      effected by ropes attached to her body and arm and to the door and window of the
      family dining-room where a temporary bed has been installed. Thanks to her robust
      constitution and to the skill of the seven-strong medical team, Juliette Gide
      eventually regains full use of her arm.

PMID- 27029138
TI  - [Scientific heritage of Professor V.V. Kucheruk (on his 100th anniversary)].

PMID- 27029139
TI  - [ON SOME DEBATABLE PROBLEMS OF THE NATURAL NIDALITY OF PLAGUE].
AB  - The communication substantiates the opinion that the theory of natural nidality
      of plague; which is based on the fundamental recognition that fleas play a
      leading role in the transmission and accumulation of the plague pathogen, cannot
      be disproved or substantially changed on the alternative weakly reasoned
      assumptions and hypotheses. All its "bottlenecks" are quite understandable when
      considering the long-term volumetric materials that have been gathered directly
      in nature and generalized in multiple publications. Plague is an obligate
      transmissive infection; its, agent is a highly specialized parasite that is
      completely associated in its vital activity with the only group of the blood
      sucking insects--fleas and that is transmitted through periodic colonization of
      warm-blooded animals for a short time. All other types of plague microbe
      persistence in nature are either occasional or minor and do not play any
      significant role in pathogen persistence in the natural foci of this disease.
      There are no strong grounds for seriously considering the attempts to revise the
      main points of the theory of natural nidality of plague, which are widely held in
      current academic publications.

PMID- 27029140
TI  - [IMPACT OF CASPIAN SEA LEVEL FLUCTUATIONS ON THE EPIZOOTIC ACTIVITY OF THE
      CASPIAN SANDY NATURAL PLAGUE FOCUS].
AB  - There is evidence that in 1923-2014 the sharp aggravations of the epizootic
      situation of plague in the area of its Caspian sandy natural focus after long
      interepizootic periods are in time with the ups of the Caspian Sea in the extrema
      of 11-year solar cycles. There were cases of multiple manifestations of plague in
      the same areas in the epizootic cycles of 1946-1954, 1979-1996, 2001, and 2013
      2014. The paper considers the possible role of amebae of the genus Acanthamoeba
      and nematodes, the representatives of the orders Rhabditida and Tylenchida in the
      microfocal pattern of plague manifestations.

PMID- 27029141
TI  - [A NATURAL PLAGUE FOCUS. IN GORNYI ALTAI: FORMATION, DEVELOPMENT, AND
      FUNCTIONING].
AB  - The paper gives the results of analyzing the data of long-term studies of the
      natural focal pattern of plague in the Gornyi Altai natural focus. It describes a
      wide range of biological processes occurring in the focus and shows the most
      important patterns of its functioning as a complex multilevel ecological system.
      The key features of the formation of the focus have been revealed. The plague
      focus in South-Western Altai has formed relatively, recently, about half a
      century ago, then it has intensively developed and its enzootic area and the
      activity of epizootic manifestations have considerably increased. This process is
      due to the space-time transformations of the basic ecological and population
      characteristics of Pallas' pika (Ochotoma pallasi), the principal vector of the
      pathogen of plague and fleas parasitizing the mammal, which is in turn related to
      the aridization of mountain steppes in South-Western Altai.

PMID- 27029142
TI  - [ON THE ORIGIN OF HYPERVIRULENCE OF THE CAUSATIVE AGENT OF PLAGUE].
AB  - The attempt to combine Yersinia pseudotuberculosis and Yersinia pestis into one
      species has been unsupported by microbiologists due to the specific features of
      the epidemiology and clinical presentations of their induced diseases and to
      basic differences in their virulence. Pseudotuberculosis is predominantly a
      relatively mild human intestinal infection transmitted through contaminated food
      and plague is an acute generalized disease with high mortality, which is most
      frequently transmitted by the bites of infected fleas. Y. pestis hypervirulence,
      the ability of single bacteria to ensure the development of predagonal
      bacteriemia in rodents, which is sufficient to contaminate the fleas, is one of
      the main events during pathogen adaptation to a new ecological niche. By
      analyzing the data of molecular typing of the representative kits of naturally
      occurring Y. pestis isolates, the authois consider the issues of formation of
      intraspecies groups with universal hypervirulence, as well as biovars that are
      highly virulent only to their major host. A strategy for searching for selective
      virulence factors, the potential molecular targets for vaccination and etiotropic
      treatment of plague, is discussed.

PMID- 27029144
TI  - [SPECIFIC FEATURES OF RELATIONSHIPS BETWEEN THE FRONTOPSYLLA LUCULENTA LUCULENTA
      (JORDAN ET ROTHSCHILD, 1923) FLEA AND THE PLAGUE PATHOGEN WITH DIFFERENT PLASMID
      COMPOSITION].
AB  - It was experimentally established that plague pathogen strains with different
      plasmid composition variously suppressed the viability of Frontopsylla luculenta
      luculenta fleas. Dead insects were most frequently observed among those infected
      with a virulent strain having the cryptic plasmid pTP33. The presence of the
      avirulent and apesticinogenic plasmid I-3480 in the fleas less deteriorated their
      state. Biofilm formation by different F.l.luculenta strains in the body was
      characterized by quantitative and qualitative differences. The strains that had
      the cryptic plasmid and were able to form the biofilm in the F.l.Iuculenta fleas
      surpassed the three-plasmid strain I-3230 and their formned aggregates achieved
      very large sizes and frequently persisted until the end of the experiment. Small
      solitary masses were generally observed in the insects infected with the three
      plasmid strain. Thus, the pTP33 plasmid potentiated the pYT plasmid-encoded
      ability to colonize the F.l.Iuculenta fleas with the plague pathogen; in this
      case the products of the pYV and pYP plasmids (or one of them) are toxic to
      ectoparasites.

PMID- 27029143
TI  - [PLAGUE IN MANCHURIA (1910-1911) AND EBOLA VIRUS DISEASE IN WEST AFRICA (2014
      2015): COMMON PREREQUISITES FOR THE DEVELOPMENT OF EPIDEMICS].
AB  - The paper gives the results of a comparative analysis of the prerequisites for
      the emergence and spread of epidemics of particularly dangerous infections, by
      using plague in Manchuria (1910-1911) and Ebola virus disease in West Africa
      (2014-2015) as examples. Analysis of literature and archival data and online
      information could reveal a number of common factors and conditions, which
      substantially contributed to the epidemics. Organization of anti-epidemic
      (preventive) measures in cases of the threatening epidemic spread, of
      particularly dangerous diseases must be based on the minimization, of the
      influence of the specific factors and conditions, which facilitate disease
      transmission in a given area in a given time.

PMID- 27029145
TI  - [THE EPIZOOTIC AND EPIDEMIC ACTIVITY OF NATURAL TULAREMIA FOCI OF DIFFERENT
      LANDSCAPE EPIDEMIOLOGICAL TYPES IN 2009-2014].
AB  - OBJECTIVE: to assess the present state of the natural tularemia foci of different
      landscape epidemiological types, by using individual focal areas as an example.
      MATERIALS AND METHODS: Epizootological monitoring and epidemiological analysis
      were conducted in the areas of natural tularemia foci of tundra (Wrangel Island),
      meadow-field (Central Federal District of the Russian Federation), flood-swamp
      (Arkhangelsk Region, Khanty-Mansi Autonomous District), and steppe (Mongolii)
      types. Small mammals (organs, blood), tularemia patients' sera, and
      environniental objects were examined. Molecular genetic and immune serological
      diagnostic assays were used. The incidence of tularemia in the past decade was
      analyzed using the maps for the epidemiological examinations of tularemia cases
      and medical reports. RESULTS: The natural foci of tularemia were established to
      continue to actively operate. There were 2913 cases of tularemia in the Russian
      Federation in 2001 to 2014. The flood-swamp natural foci, in which there were
      summer transmissive tularemia outbreaks, the largest of high occurred in Khanti
      Mansiysk in 2013 when a total of 1005 people fell ill, are a special epidemic
      hazard. Analysis of the tularemia outbreaks suggests that there is a need for
      continuous epizootological monitoring of the areas of natural tularemia foci for
      the timely prediction and prevention of epidemic complications. It is noted that
      there is an unfounded reduction in the scope of preventive measures, and
      immunoprevention in particular, and a weaker control of the antitularemia immune
      status in the population residing in the area of active natural foci of
      tularemia.

PMID- 27029146
TI  - [RATS OF THE GENUS RATTUS AS HOSTS FOR NATURAL FOCAL INFECTIOUS AGENTS].
AB  - The paper reviews the significance of rats of the genus Rattus as hosts for
      zoogenous infections in a genus formation area (Southeast Asia) as compared to
      the invasion part of the genus area. The rats of the genus Rattus and their
      related disease agents are shown to be a uniqe model for the formation and
      development of a host-pathogen system. In the modern period of urbanization
      growth, the rats are among few species of warm-blooded vectors that can maintain
      the anthropurgic foci of feral nidal infections in the cities and towns and
      transmit their pathogens to the urban population. There are all prerequisites for
      the high activity of these foci in the native area of rats. By having settled,
      the rats have carried infectious agents outside this area along all continents in
      historical times. During invasions, the rats have become carriers of many other
      infections.

PMID- 27029147
TI  - [ECOLOGICAL AND GEOGRAPHIC ANALYSIS OF THE SPREAD OF MITES OF THE FAMILY
      TROMBICULIDAE IN MONGOLIA].
AB  - The paper gives data on the fauna of chigger mites (Thrombiculinae), the
      ectoparasites of small mammals in Mongolia. The ecological and geographic
      analysis could reveal the major abiotic and biotic determinants of the spread of
      the chigger mites and make a map of their potential area.

PMID- 27029148
TI  - [The mapping of focal areas as the basis for preventing zoonotic cutaneous
      leischmaniasis].

PMID- 27029150
TI  - Advocacy.

PMID- 27029149
TI  - [EFFECT OF PYRETHROIDS ON TAIGA TICKS (IXODES PERSULCATUS IXODIDAE)].
AB  - Nonspecific prevention of infections, the agents of which are transmitted by
      Ixodes ticks, is aimed at stopping the suction of the ticks to humans and is
      substantially based one the use of acaricides. The most interesting group of
      compounds to be used to individually protect humans is pyrethroids that cause
      different nerve conduction disturbances in the ticks, which result in their
      paralysis and death more significantly rapidly than the compounds from other
      chemical groups. The effect of 8 pyrethroids was investigated when the taiga
      ticks were in contact with the tissue treated with the compounds. The
      relationship of the chemical structure of pyrethroids with their acaricidal
      activity was analyzed from motor activity values and knockdown time. The test
      pyreithroids, in order of decreasing acaricidal activity, are imiprothrin
      cyphenothrin, cyfluthrin, alpha-cyperamethrin, zeta-cyperimethrin fenothrin,
      flumethrin.

PMID- 27029151
TI  - Health Service Utilization of Children in Delaware Foster Care, 2013-2014.
AB  - OBJECTIVE: Children in foster care represent some of the most vulnerable children
      in the U.S. Their higher prevalence of a range of physical and behavioral health
      problems can lead to greater health care utilization and higher costs. However,
      many children in foster care have undiagnosed conditions and unmet needs. The
      purpose of this study was to provide a description of health services accessed by
      children in foster care in Delaware. The data serves as a baseline and informs
      current efforts to improve the health care of children in foster care. We
      analyzed rates of emergency room visits, behavioral health visits,
      hospitalizations, and costs of care for children in foster care and made
      comparisons with other children participating in Medicaid. We also looked at
      utilization before and after entry into care and assessed rates of appropriate
      medical screening for children on entering foster care. This study was conducted
      as part of a larger analysis guided by the Delaware Task Force on the Health of
      Children in Foster Care with funding appropriated by the Delaware General
      Assembly. METHODS: Using a unique identification number, we linked Medicaid
      claims data with demographic information and characteristics associated with
      foster care from the Delaware Department of Services for Children, Youth and
      Their Families. We examined diagnoses, patterns of utilization, and costs for
      children in foster care (n = 1,458) and a comparable cohort of other children in
      Medicaid (n = 124,667) during fiscal years 2013 and 2014. RESULTS: Compared with
      other children in Medicaid, children in foster care had similar rates of
      emergency department utilization, but relatively high rates of outpatient
      behavioral health visits. Similarly, compared with other children in Medicaid,
      those in foster care had particularly high rates of psychotropic drug
      utilization. Entry into foster care was associated with increased utilization of
      overall health care services, including receipt of well-child care. However, just
      31 percent of those new to foster care met the recommended guidelines for a
      preventive screening in their first 30 days. CONCLUSIONS: Because of the
      challenges in meeting screening policies for children entering foster care,
      collaboration among providers, state administrators, and policymakers is
      essential to guide improvement. Specifically, stakeholders should look for ways
      to improve the timeliness of preventive screenings and coordination of care. The
      high rate of behavioral health visits suggests the need to improve integration of
      behavioral health care into primary care.

PMID- 27029152
TI  - Cardiology Critical Care Crisis: Can Working Across The Aisle Be The Salvation?
AB  - There are many changes in the demographics of patients admitted to Cardiac Care
      Unit (CCU) due to the aging of US population and coexistence of chronic
      illnesses, such as diabetes mellitus, hypertension, renal dysfunction, and
      obstructive lung disease. There is increasing evidence that intensivist staffing
      in the critical care settings is associated with not only improvements in both
      Intensive Care Unit (ICU) and in-hospital mortality, but also with better medical
      resource use. Evidence for decreased mortality has led to increased involvement
      of critical care trained physicians in multidisciplinary care teams in both
      medical and surgical ICUs, a trend that has not been adopted to any significant
      extent in CCUs. A partnership between cardiologists and critical care specialists
      may offer a better roadmap to deal with cardiac critical care crisis, provide
      better care for our patients, and prepare the next generation of cardiologists to
      deal with emerging challenges in the field.

PMID- 27029153
TI  - [HYGIENE: STRUCTURE OF INNOVATIVE RESEARCH STUDIES IN RUSSIA (2000-2014)].
AB  - There was analyzed the array of 1548 dissertations on the scientific specialty
      14.02.01 (former specification 14.00.07) "Hygiene". Over period of 2000-2014 to
      the Dissertation Committee in Russia there were annually submitted (103 +/- 10)
      theses, which include (21 +/- 3) doctoral dissertations and (83 +/- 8) candidate
      dissertations. Doctoral dissertations accounted for 20,1%, dissertations in
      medicine--89.3%. There was established not only the decline in the number of
      theses in hygiene, but the reduction of their proportion in the total array of
      all medical and biological dissertations in Russia. The conjugacy of the trend
      curves of the total stream of dissertations in medicine and biology in Russia and
      in hygiene is considered to be not very high (r = 0.54). In the total structure
      of dissertation works on General Hygiene accounted for 22.7%, Community Hygiene-
      15.45%, Occupational Hygiene--19.6%, Children's and Adolescents' Hygiene--24.7%,
      Nutrition Hygiene--8.2%, Radiation Hygiene--2.3%, in Rural Hygiene--1.2%,
      Hospital Hygiene-- 3.4%, Military Hygiene--2.3% correspondingly. There is pointed
      the development gap between the research studies in hygiene and tendency in
      training of high class health care professionals' in Russia.

PMID- 27029154
TI  - [THE REGULARITIES OF DEVELOPMENT OF CANCER MORBIDITY AND MORTALITY RATE OF THE
      POPULATION IN THE REPUBLIC OF TATARSTAN AND FINLAND].
AB  - There were revealed gender differences in cancer morbidity and mortality rate in
      the Republic of Tatarstan over the period from 1996 till 2013. The morbidity rate
      was increased by 1.54 times in both urban and rural areas. The morbidity rate
      level in men was two times higher than in women. The maximum share of new cases
      of cancer morbidity according to the primary lesion in men in Finland in 2008
      2012 was noted in the age groups of 60-64, 70-79 and 85 years and older

PMID- 27029155
TI  - [ASPECTS OF HEALTH-SAVING MOTIVATION IN CHILDREN OF THE PRESCHOOL GROUP].
AB  - The problem of education of culture of health in children ofpreschool age is
      actual and sufficiently complicated. It is important at this age stage to create
      in children the first knowledge and practical skills of a healthy lifestyle. The
      example of parents has considerable impact on adoption of health saving behavior
      of a child. For identification of motivations of parents in the sphere of
      protection and strengthening of health of their children there was performed
      questionnaire survey of parents of preschool children according to specially
      developed questionnaire. A half of parents are established to be unable to devote
      sufficient time to health of the child due to engrossment. A considerable portion
      of parents doesn't keep a healthy lifestyle, differs in low medical and sports
      activity. The main motivation of parents is the motivation on recovery of the
      child after the disease, but not on preservation, strengthening and development
      of health.

PMID- 27029156
TI  - [THE USE OF THE SCREENING-ASSESSMENT OF THE HEALTH LEVEL OF SCHOOLCHILDREN IN THE
      PREVENTIVE WORK OF THE TEACHER].
AB  - In the paper there are presented results of the research performed with the aid
      of the automated software complex "Health Express". There was determined the role
      of the participation of the pupil himself in an assessment of a state of his
      health, indices ofphysical development and psychological characteristics. There
      was proved the expediency of the active involvement of schoolchildren to the
      shaping of the program of activities on preservation and strengthening of a state
      of their health. There was shown the role of preventive work of the school
      teacher.

PMID- 27029157
TI  - [INFORMATION AWARENESS OF STUDENTS--FUTURE TECHNOLOGY FOR HEALTHY LIFESTYLES
      TEACHERS AND TRAINING IN THEIR EDUCATIONAL ACTIVITIES IN AREA OF HUMAN HEALTH
      PRESERVATION].
AB  - In the article there are presented results of the questionnaire survey of
      students--future technology for healthy lifestyles teachers on issues of shaping
      of health and a healthy lifestyle. There is given an estimation of the degree of
      the formedness in students adjustment for healthy lifestyle, including eating
      behavior and nutrition ration. There were determined basic directions of the
      shaping of the health-saving competence of the school teacher.

PMID- 27029158
TI  - [SELF-ASSESSMENT OF HEALTH STATUS AND LIFESTYLE AMONG STUDENTS OF PEDAGOGICAL
      UNIVERSITY].
AB  - The life style is considered as one of the leading factors determining human
      health. The problem of maintaining a healthy lifestyle now isn't solved yet,
      despite its broad promotion, since in the student's environment risk factors for
      health are still rather widespread In the paper there are presented data of
      sociological questionnaire survey lighting a self-assessment of health status,
      features of a life style among students of the physical and mathematical faculty
      of the Pedagogical University. There is given an assessment of the spread of risk
      factors for health in this category of respondents.

PMID- 27029159
TI  - [CRITICAL FACTORS OF THE LIFE QUALITY OF ADOLESCENTS].
AB  - There was performed the discussion of the shaping of the quality of life of
      adolescents. There are considered possibilities and problems of the determination
      of the quality of life. There are presented data of their own studies of
      adolescents with the use of anthropometric, psychometric and sociometric methods.
      It is proposed to consider the priority critical factors of life quality of
      adolescents the level of material well-being and psychological climate in the
      school, physical and social activity, behavioral risk factors.

PMID- 27029160
TI  - [COMPENSATORY CAPACITIES OF THE CHILD'S BODY IN THE CONDITIONS OF AEROTECHNOGENIC
      LOADING].
AB  - The purpose of the investigation was in the study of the influence of
      aerotechnogenic load on children and adolescents as a cause of the occurrence of
      diseases and exacerbation of the course of the chronic disease. There was
      performed an analysis of the daily air pollution by nitrogen dioxide, particulate
      matter, soot, sulfur dioxide, formaldehyde, phenol, nitrogen oxide, carbon
      monoxide, and appealability for medical aid of children and young people residing
      in the area with the high level of aerotechnogenic load. In the course of the
      work the correlation analysis was used in three ways: when the date of
      appealability for medical care coincided with daily indices of the level of air
      pollution; with delayed of 1 day (shift of data was carried out for 1 day); with
      delayed of 2 days (shift of data was carried out for 2 days). The number of
      examined children's population under the age of 14 years and adolescents up to 17
      years accountedfor 7303 children, the study period was 1 year. In the course of
      the work there was established a causal relationship between the level of air
      pollution and the appealability of the children for the medical care: the pair
      correlation coefficients for certain classes of diseases amounted from 0.16 to
      0.82. It is revealed that the highest number of requests for medical assistance
      was established to be accounted for the date following the date after exposure to
      elevated concentrations of pollutants in ambient air Therefore, the
      aerotechnogenic load, to which the human body is exposed to throughout life, from
      childhood can be considered as a stress factor that reduces the compensatory
      capacities.

PMID- 27029161
TI  - [HYGIENIC ASSESSMENT OF NUTRITION IN STUDENTS OF INSTITUTIONS OF MEDICAL
      PROFILE].
AB  - In the article there are presented the results of the evaluation of nutrition
      rations of students of educational institutions of medical profile. There was
      performed the method of questionnaire survey. The questionnaire was responded by
      199 medical college students and 399 students of medical university. It was found
      that the nutrition rations were established to fail to meet the requirements of
      sound nutrition. In particular, 30% of observed respondents fail to keep up three
      four meals daily. There is no hot dish in the daily ration. There is revealed a
      deficit of consumption of protein foods: meat, fish, dairy products, eggs with an
      excess of digestible carbohydrate. Unbalanced nutrition is a risk factor for
      alimentary-related diseases.

PMID- 27029162
TI  - [ASSESSMENT OF ANXIETY AND DEPRESSION STATES IN ADOLESCENTS AS THE INITIAL STAGE
      FOR PSYCHOPROPHYLACTIC WORK IN SCHOOL].
AB  - In the article there are presented data of the study of psycho-physiological
      indices of higher nervous activity in adolescents, there are established the
      interrelationships between the type of temperament and the level of performance
      of schoolchildren. There was made en evaluation of the prevalence of depressive
      states in 8th graders, defined the frequency of occurrence of various levels of
      anxiety. There are denoted basic directions of the preventive work on the anxiety
      level down in senior schoolchildren; as well as measures aimed at reduction of
      the number of students with depressive states.

PMID- 27029163
TI  - [THE NUTRITIONAL SUPPORT OF STUDENTS--ATHLETES OF THE MEDICAL UNIVERSITY IN THE
      PRECOMPETITIVE PERIOD].
AB  - The aim of the study was the assessment of the protein-vitamin correction of the
      food ration of student-athletes in the precompetitive period The relevance of
      nutritional support was determined by irrational and unbalanced nutrition and
      comorbidities in students, not infrequently due to insufficient material support
      of students, the schedule drawn up without taking in account their
      biorythmological activity. Enrichment of the diet of student-athletes was
      performed with the use of normoprotein--dry composite protein mixture (DCPM) in
      daily dose of 30 g). Normoprotein is a source of highly digestible proteins,
      dietary fibers, vitamins, minerals, taxifolin, which is recommended, also for the
      dietary (medical and preventive) nutrition of children in organized collectives.
      A prerequisite for the administration of the drug was the assessment of the
      health in 50 student-athletes in the Health Center questioning of students for
      the acquisition of information concerning the presence or absence of complaints,
      allergic reactions, evaluation of the life quality, and also written consent for
      the use of normoprotein.

PMID- 27029164
TI  - [IDENTIFICATION OF RISK FACTORS IN THE PRODUCTION OF SYNTHETIC RUBBER].
AB  - There was performed the identification of risk factors at the production of
      synthetic rubbers, priority factor of them is chemical. Results of researches
      testify to need of continuous monitoring of exposure of chemicals on atmospheric
      air of the residential territory for the purpose of securance of hygienic and
      ecological safety of the city.

PMID- 27029165
TI  - [METHODS OF MODELING TEMPERATURE REGIMES IN TESTS OF POLYMER CONTAINING BUILDING
      MATERIALS AND FURNITURE FOR HOMES AND PUBLIC BUILDINGS].
AB  - This article is devoted to the modeling of temperature conditions in performance
      of research of polymer containing building materials and furniture. The authors
      draw attention to the different conditions of modeling used in the existing
      guidance documents, and provide a unified approach to this problem, namely in the
      performance of the study to use the temperature regime, which corresponds to the
      maximum value of the optimum temperature range for residential and industrial
      premises.

PMID- 27029166
TI  - [HYGIENIC ASSESSMENT OF NOISE FACTOR OF THE LARGE CITY].
AB  - The article is devoted to the problem of the negative impact of traffic noise on
      the health and living conditions of the population in conditions of the large
      city. Every day on the streets there are appeared more and more different modes
      of transport, and to date almost all transportation network has reached his
      traffic performance. The increase in traffic noise certainly has an impact on the
      human body. The most common and intense noise is caused by the traffic of urban
      automobile and electric transport. This is explained by the existence of the
      heavy traffic (2-3 thousand crews/h) on almost all main roads in historically
      emerged parts of the city. In addition, sources of external noise in the city can
      be a railway running in residential zone, access roads, industrial enterprises,
      located in close proximity to residential areas and on the borders of residential
      zones, planes of military and civil aviation. For the evaluation of the different
      noises sound levels were measured with the use of sound level meters. The most
      common parameter for the assessment ofthe noise generatedfrom motor vehicles on
      residential areas and usedfor the noise characteristics of the traffic flows, is
      the equivalent sound level/A EQ dB. This parameter is used in the majority of
      normative-technical documentation as hygienic noise standard. With the aim of the
      assessment of noise exposure there were selected 122 control points at
      intersections of roads of different traffic performance where there were made
      instrumental measurements the equivalent sound level, followed by its comparison
      with permissible levels.

PMID- 27029167
TI  - [HYGIENIC ASSESSMENT OF RADIATION DOSES TO THE POPULATION OF THE VORONEZH REGION
      FROM SOURCES OF IONIZING IRRADIATION].
AB  - In the article there are presented the results of evaluation of radiation doses
      to the population of the Voronezh region from natural and man-made sources of
      ionizing radiation. It was established that in the structure of the collective
      dose of the population of the Voronezh region annually the dose from natural
      sources of ionizing radiation leads, ranging from 74.96% to 76.68%. According to
      the evaluation of indices characterizing the level of the impact of sources of
      ionizing radiation there was no recorded exceedance of statutory criteria.

PMID- 27029168
TI  - [STUDY OF THE IMPACT OF WHEAT GERM CAKE OIL AND FLOUR ON INDICES OF ENERGY
      EXCHANGE IN STUDENTS AND TEACHERS OF HIGH SCHOOL].
AB  - There were obtained data which confirm the increase of efficiency of gas exchange
      processes in students and teachers of the engineering high school in the daily
      use of at least 3.5 g of wheat germ oil and 50 g of wheat germ cake flour without
      the correction of the basic ration. The study of the exhaled gas-air mixture
      showed in all age groups the gain in the concentration of carbon dioxide and the
      decline of concentration of oxygen by the 0.20-0.30%. There was established the
      increase of blood oxygenation level in all subjects. There was demonstrated the
      relationship between the depth of the alteration of these parameters with age,
      and regular physical activity in studied cases.

PMID- 27029169
TI  - [BLOOD INDICES AT SLAUGHTER OF BIRDS UNDER THE CONDITIONS OF THE OPERATING
      ENTERPRISES].
AB  - Implementation of non-waste technologies at the poultry establishments supposes
      the involvement of by-products of slaughter of birds, in particular, the blood as
      a source of protein and unique organic iron. For the feasibility of reasonable
      approaches to the possible use of birds' blood in the production of
      technologically acceptable emulsions there was studied and identified by the
      method of PCR analysis the species composition of microflora in the process of
      blood collection and storage, as also the environment of the slaughterhouses,
      there was considered the dynamics of the growth of microorganisms and measures
      for its limitation.

PMID- 27029170
TI  - [HYGIENIC ASPECTS AND PROSPECTS FOR DOMESTIC PRODUCTION OF VEGETABLE PROTEINS].
AB  - There was performed an estimation of the protein inanition and possibilities for
      its resolution by means of capture of plant sources. There were analyzed the
      composition and properties of domestic agricultural crops in comparison with soy
      and there are established prospects of their use in technology ofconcentration of
      the protein component.

PMID- 27029171
TI  - [EVALUATION OF THE BACTERIOSTATIC EFFECT OF IMMOBILIZED ON COLLAGEN CARRIER
      ANTIBIOTICS AND SILVER IONS IN PROVISION OF THE ASEPTIC STATE OF THE TISSUE
      WOUNDS].
AB  - In the treatment of tissue wounds practically all the time there is necessary the
      establishment of aseptic conditions in the area of the damaged tissue. In modern
      medical practice quite a while the use of materials on the basis of collagen
      aroused widespread. The aim of the study was an assessment the bacteriostatic
      properties both of collagenic substance with the antibiotics immobilized on it,
      and ions of silver also. The presence on a surface of collagen of a large number
      of active functional groups allow to use it as a matrix for an immobilization of
      various biologically active and medicinal agents. Authors performed an assessment
      of possibility of an immobilization of antibiotics on the collagenic carrier. The
      purpose of an immobilization was in the prolongation of the impact of an active
      component--Polymyxin-M or Gentamycin. Besides aseptic effect, availability of
      specific amino acids of collagen will promote the acceleration of the reparative
      processes in a wound. There were performed investigations on determination of
      bacteriostatic effect of immobilized on the protein carrier (collagen of
      hydrobionts) antibiotics, and silver ions also. Bacteriostatic effect was
      estimated by the disco--a diffusive method with use of E. coli as test culture.
      Results of the studies showed that the delivered preparation had bacteriostatic
      effect on the test culture. At that the area of a zone of a growth inhibition in
      case of the of use--Polymyxin was 1.3 time more than, than in case of the use of
      a preparation of Gentamycin. The obtained collagenic substances of an origin with
      the immobilized bacteriostatic components and ions of silver have considerable
      prospects and real opportunity in the delivery of aseptic preparations of a
      domestic production. Taking into account the available data in further there is
      planned the development of aseptic preparations with the occluded biologically
      active agents and nanoparticles of metals for providing an aseptics and
      acceleration the reparative processes in the treatment of open wounds.

PMID- 27029172
TI  - [SANITARY-HYGIENIC ASSURANCE OF THE PRODUCTION OF THE SUGAR MANUFACTURE].
AB  - Bactericidal preparations currently used in the beet sugar manufacture, fail to
      provide the required microbiological purity of the finished product.
      Experimentally there was proved the feasibility of an application of the new
      preparation on the base of dichloroisocyanuric acid at initial stages of the
      production. There is proposed a combined physical-chemical method of the process
      water purification with the use of impulse magnetic treatment and various
      sorbents.

PMID- 27029173
TI  - [SANITARY-TECHNOLOGICAL APPROACHES OF THE IMPROVEMENT OF THE BREAD PRODUCTION
      WITH THE USE OF HOP COMPOSITION].
AB  - In the aricle there are considered the processing technologies for the
      improvement of the quality of leaven and sprouted wheat grain products, which
      being notable for unstable microflora need for the quality control and research
      of micro biological indices. The use of hop composition was established to give
      rise in the increase in the quality of the thick grain leaven. It is proved that
      in this microbiological indices of bakery products advanced, the number of
      mesophilic aerobic and facultative anaerobic microorganisms falls, the duration
      of storage without signs of growth of molds increases. This work is of practical
      interest in refining the quality of bakery sprouted wheat grain products and
      their microbiological purity.

PMID- 27029174
TI  - [REDUCTION OF THE CONTENT OF AFLATOXIN-FORMING FUNGI IN CONTAMINATED GRAINS BY
      METHODS OF HYDROTHERMAL TREATMENT].
AB  - Microscopic fungi affecting grain and products of its processing, under certain
      conditions, are capable of producing over 100 mycotoxins, some of which are
      carcinogenic. Mycotoxins are falled to the most dangerous contaminants of food
      and compound animal feedstuff, they possess toxicity, mutagenic and carcinogenic
      properties. The most toxic and dangerous carcinogens are aflatoxins which affect
      on virtually all cells of the body of the human and agricultural animals,
      provoking the occurrence of diseases--aflatoxicoses. Aflatoxins give rise to
      encephalopathy and fatty degeneration of internal organs. The World Health
      Organization mentions aflatoxins as a cause of the origin of cancer. Currently in
      Russia there is a real danger of the negative impact of mycotoxins on farm
      animals in feeding grain affected by aflatoxins. The gain in the number of
      aflatoxicoses is a serious hygienic problem. This is related with the wide spread
      of producers of aflatoxins in nature and also with the intensive trade of grain
      and products of its processing between countries, a lack of control over their
      content. Detoxification of the affected products is an actual task, because its
      use causes irreparable harm to human health andfarm animals. Currently there are
      known several ways of inactivation of aflatoxins in the grain, based on the use
      of hydrothermal treatment. IR heat treatment, ultraviolet irradiation and
      extrusion were established to be the most rational approaches, providing the
      reduction offungi in the grain of aflatoxin-forming fungi by 80 ... 100%,
      aflatoxin B1--by the 76... 100% and a decrease in the degree of toxicity by 2.3
      times. There are presented experimental data of various ways of disinfecting
      grain and appropriateness of their application in practice.

PMID- 27029175
TI  - [IMPLEMENTATION OF MEASURES FOR OCCUPATIONAL HYGIENE AT ENTERPRISES OF BREWING
      INDUSTRY].
AB  - In the paper there are considered the legal basics of the occupational hygiene of
      brewing production: acts, bylaws and normative legal acts. There are
      characterized types of supervision and control (state, departmental, public)
      implementing the abidance of the sanitary legislation at the enterprises of the
      brewing industry. There are presented sanitary and hygienic requirements to the
      enterprises of the brewing industry. There are designated measures of
      occupational hygiene of brewing production: a sink, cleaning--removal of various
      pollutions, and also disinfection--process of the decline in quantity of
      microorganisms to safe level. There are considered some characteristics of
      pollutions which are subject to removal at various stages ofproduction of beer
      and stages of sanitary processing of brewing systems according to chemical
      properties of substances.

PMID- 27029176
TI  - [HYGIENIC ASSESSMENT OF NUTRITION IN VEGETARIANS AND PEOPLE WITH MIXED FEEDING].
AB  - There was performed a comparative analysis of the actual nutrition of inhabitants
      of the city of Omsk with mixed feeding (n = 50), and representatives of different
      types of vegetarians: raw food diet (n = 12), veganism (n = 14), lacto-ovo
      vegetarians (n = 14). There were revealed differences in consumption of food and
      food substances in persons with different types of food. There was established
      insufficient energy value, reduced intake of protein, fats, carbohydrates,
      vitamin B12 in the diet of vegans and raw foodists. There was determined the
      availability of vitamin B12 by the analysis of this substance in the blood serum
      by mean of standard chemiluminescent immunoassay. Vitamin B12 deficiency was
      revealed in vegans and raw foodists. There were substantiated such basic
      directions ofelimination of the deficit of nutrients and calories in the diet of
      vegetarians as the careful planning and assortment of products, as well as the
      use of vitamin-mineral complexes.

PMID- 27029177
TI  - [INFLUENCE OF THE REGULAR INTAKE OF FERMENTED MILK PRODUCTS ENRICHED BY
      MICRONUTRIENTS ON SOME INDICES OF IRON METABOLISM IN ADOLESCENTS INVOLVED IN
      SPORTS].
AB  - There was performed an experimental study of the influence of regular intake
      offermented milk enriched by products "Bifidin" and "Prolacta" on indices of iron
      metabolism in adolescents of 12-17 years, involved in sports (n = 94). In all
      study participants there was made double blood test (every 60 days), there were
      determined the levels of hemoglobin, serum iron, serum ferritin, C-reactive
      protein. The intervention in the main group (n = 68) was in daily intake
      offermented milk product in a volume of 200 ml (1 Cup) in addition to the normal
      diet within 2 months, including 35 cases who had used the bioproduct "Bifidin"
      and 33 persons- bioproduct "Prolacta". The control group was consisted of 26
      persons from the adolescents engaged in the same sections, but not taking
      additional fermented milk drinks. The average values of all studied indices in
      adolescent athletes of the main and control groups before and after the
      intervention were consistent with reference values. Latent iron deficiency was
      detected in 23.4 +/- 4.4% of adolescents involved in sports. At the second point
      of the research in two months of intake of enriched dairy products in the main
      group there was noticed the gain in levels of serum iron, ferritin, and the
      decline of the concentration of C-reactive protein. The results of the study
      allow us to consider enriched dairy products "Bifidin" and "Prolacta" as one of
      the components of complex measures of prophylaxis of hypovitaminosis and
      microelementoses in adolescents who are actively involved in sports.

PMID- 27029178
TI  - [SOCIO-EPIDEMIOLOGICAL ASSESSMENT OF THE SITUATION ON VIRAL HEPATITIS B IN THE
      VORONEZH REGION].
AB  - In the present paper there is presented an analysis of the incidence of viral
      hepatitis B (HBV) in the territory of the Voronezh region in the dynamics and the
      effectiveness of the implementation of the specific prevention over the past
      fifteen years. During this period of time, there is observed a stable tendency to
      the decrease in the incidence of chronic forms from 100.2 per 100 thousand
      population in 2000 to 21.7 per 100 thousand population in 2014. When ranking the
      Voronezh region on the prevalence of HBV there were identified eight most
      affected districts, including the city of Voronezh. There was noted a distinct
      regularity for the reduction of the incidence of HBV in dependence on the
      inoculation rate.

PMID- 27029179
TI  - [THE EFFECTIVENESS OF VACCINATION AGAINST DIPHTHERIA IN THE VORONEZH REGION].
AB  - The purpose of the study was the assessment of the effectiveness of vaccination
      against diphtheria in the Voronezh region over the epidemic period of 1993-1997
      and epidemiological welfare during 2010-2014. MATERIALS AND METHODS: of the
      study: data of the official statistical reporting--forms number 1, 6, the serum
      level of antitoxic antibodies to diphtheria in 19319 healthy individuals were
      analyzed with the aid of epidemiological (descriptive and evaluative),
      immunological and statistical methods. RESULTS: During the epidemic rise of
      diphtheria (1993-1997) 75% of cases were amounted to the adult population of the
      Voronezh region, half of them--were not immunized against diphtheria. In 1993
      there was begun mass vaccination of adult population, immunization coverage by
      1998 reached 95%. According to seromonitoring data the share of seronegatives to
      diphtheria among cases examined during the period of 1995-2000 accountedfrom 11.9
      to 24.9%. During the period of sporadic morbidity (1998-2007 years) among
      patients the 80% of cases have been vaccinated with an interval from the last
      inoculation of 3-5 years, which casts doubt on the effectiveness of vaccines.
      Since 2008 the incidence of diphtheria in the Voronezh region was not recorded.
      Against the background of 98% coverage of vaccination of the total population,
      the share of seronegatives for the last 5 years have decreased by 2.5 times and
      in 2014 reached the required performance. CONCLUSION: Documented inoculation
      indices fail to reflect the level of the actual protection against infection. In
      the conditions of the absence of the morbidity only serological monitoring is an
      objective criterion of the protectability of the population from infection.

PMID- 27029180
TI  - [METHOD OF INCREASING MICROBIOLOGICAL PURITY OF POWDER FROM COCOA-VELLA].
AB  - In the article there is described in detail the characteristic of the product of
      processing cocoa beans--cocoa-vella, there is presented a comparative analysis of
      the chemical composition, quality indices, the dispersive pattern,
      microbiological indices of the powder from the cocoa-vella in comparison to cocoa
      powder, obtained by traditional technology from the core of the cocoa beans. To
      improve the microbiological purity of the powder from the cocoa-vella there was
      suggested to be the modern and environmentally safe manner for the preparation of
      the powder The use of cocoa-vella disinfecting power by means of the
      electromagnetic field of ultrahigh frequency (RF EMF) was established to allow to
      obtain a product that meets the requirements of Technical Regulations of the
      Customs Union (TRCU 021/2011) on Food Safety. This work is of practical interest,
      since it helps to improve the safety of the powder from the cocoa-vella, and thus
      the quality of confectionery and food products based on it, which is relevant in
      terms of the management of a healthy diet.

PMID- 27029181
TI  - Public Education, Strategic Plan, Think Tank Report Highlight Meeting.

PMID- 27029182
TI  - Reflections: Awesome 2015, Even Better 2016.

PMID- 27029183
TI  - It's Not You, It's Me: The Power of Exit Interviews.

PMID- 27029184
TI  - Oral and Maxillofacial Pathology. Case of the Month. Primary Syphillis.

PMID- 27029185
TI  - Will Your Practice Be Ready if Death or Illness Strikes?

PMID- 27029186
TI  - How to Properly Manage Debt.

PMID- 27029187
TI  - Dentistry Should Adopt Strategies from Large Hospital Networks.

PMID- 27029188
TI  - Erratum to: Is self-weighing an effective tool for weight loss: a systematic
      literature review and meta-analysis.

PMID- 27029189
TI  - Analysis of the mechano-acoustic influence of the tympanic cavity in the auditory
      system.
AB  - BACKGROUND: The main objective of this paper is to study the mechanical influence
      of the tympanic cavity (TC) in the auditory system (AS). It is done for a
      frequency range from 0.1 to 20 kHz and the pressure source was applied in the
      external ear canal (EEC) entrance. METHODS: Numerical simulations were developed
      for seven different models by means of finite element model. On the basis of an
      EEC finite elements model, the additional elements are coupled and removed in
      order to evaluate the contribution of the TC. Tympanic membrane, ossicular chain,
      simplified cochlea and TC were modeled and simulated in four different
      combinations. RESULTS: Pressure, velocity, and displacement measures were
      obtained in AS key points in order to be compared with experimental results. Umbo
      and stapes transfer functions have been represented. CONCLUSIONS: The main
      conclusion is that we find evidence that the presence of the TC in the AS
      introduces a second resonance in middle ear transfer functions at frequencies
      above 3 kHz.

PMID- 27029190
TI  - Sustained delivery of siRNA/PEI complex from in situ forming hydrogels potently
      inhibits the proliferation of gastric cancer.
AB  - BACKGROUND: Gastric cancer remains a major cause of mortality and morbidity
      worldwide. In recent years, gene-based therapeutic strategies were confirmed
      promising in cancer inhibition and attracted great attention. RNA interference
      (RNAi) is a powerful tool for gene therapy and has been widely employed to aid in
      treatment for various diseases, especially cancers. However, effective delivery
      of small interfering RNA (siRNA) to target cells in vivo remains a challenge for
      that it is prone to degradation and only lasts a few days in rapidly dividing
      cells. METHODS: Due to its biocompatibility and well-established safety profile,
      collagen represents a favourable matrix for in-site drug delivery. In the study,
      collagen hydrogel was used as carriers to test the feasibility of localized and
      sustained delivery of Id1-targeted siRNA for in vivo gastric cancer inhibition.
      To enhance the siRNA delivery, cationic polyethylenimine (PEI) was further
      emplored for scallold modification. The efficacy of siRNA delivery and cancer
      inhibition were evaluated with multimodality of mehods in vitro and in vivo.
      RESULTS: Our results showed that addition of polyethylenimine (PEI) to collagen
      can facilitate entry of Id1-siRNA into target cells, prolong the silencing
      effect, and further inhibit tumor growth both in vitro and in vivo. CONCLUSION:
      This collagen-based delivery system may facilitate the pathogenesis elucidation
      and design of effective therapies against gastric cancer.

PMID- 27029191
TI  - Recent developments in the enzymatic O-glycosylation of flavonoids.
AB  - The glycosylation of bioactive compounds, such as flavonoids, is of particular
      relevance, as it modulates many of their pharmacokinetic parameters. This article
      reviews the literature between 2010 and the end of 2015 that deals with the
      enzymatic O-glycosylation of this class of compounds. Enzymes of
      glycosyltransferase family 1 remain the biocatalysts of choice for
      glycodiversification of flavonoids, in spite of relatively low yields. Transfers
      of 14 different sugars, in addition to glucose, were reported. Several
      Escherichia coli strains were metabolically engineered to enable a (more
      efficient) synthesis of the required donor during in vivo glycosylations. For the
      transfer of glucose, enzymes of glycoside hydrolase families 13 and 70 were
      successfully assayed with several flavonoids. The number of acceptor substrates
      and of regiospecificities characterized so far is smaller than for
      glycosyltransferases. However, their glycosyl donors are much cheaper and yields
      are considerably higher. A few success stories of enzyme engineering were
      reported. These improved the catalytic efficiency as well as donor, acceptor, or
      product ranges. Currently, the development of appropriate high-throughput
      screening systems appears to be the major bottleneck for this powerful
      technology. 

PMID- 27029192
TI  - NetMHCpan-3.0; improved prediction of binding to MHC class I molecules
      integrating information from multiple receptor and peptide length datasets.
AB  - BACKGROUND: Binding of peptides to MHC class I molecules (MHC-I) is essential for
      antigen presentation to cytotoxic T-cells. RESULTS: Here, we demonstrate how a
      simple alignment step allowing insertions and deletions in a pan-specific MHC-I
      binding machine-learning model enables combining information across both multiple
      MHC molecules and peptide lengths. This pan-allele/pan-length algorithm
      significantly outperforms state-of-the-art methods, and captures differences in
      the length profile of binders to different MHC molecules leading to increased
      accuracy for ligand identification. Using this model, we demonstrate that
      percentile ranks in contrast to affinity-based thresholds are optimal for ligand
      identification due to uniform sampling of the MHC space. CONCLUSIONS: We have
      developed a neural network-based machine-learning algorithm leveraging
      information across multiple receptor specificities and ligand length scales, and
      demonstrated how this approach significantly improves the accuracy for prediction
      of peptide binding and identification of MHC ligands. The method is available at
      www.cbs.dtu.dk/services/NetMHCpan-3.0 .

PMID- 27029193
TI  - Professional Issues of International Genetic Counseling Students Educated in the
      United States.
AB  - International students have unique personal and academic challenges during their
      training in genetic counseling programs across the United States (U.S.). Previous
      research has explored their motivations and experiences; however, there is scant
      research on how their international status affects the post-graduate experience.
      The current study used semi-structured phone interviews to explore the
      professional issues that international students face throughout their educational
      and professional careers. Twenty-six participants were interviewed including
      international genetic counseling students in their second years of training and
      international genetic counselors who graduated from a U.S.-accredited program.
      Participants included six, second-year students, twelve genetic counselors
      employed in the U.S., six employed in Canada, and one employed in the United
      Kingdom (U.K.). Qualitative analysis of interviews captured the common
      experiences and challenges international students faced during their training and
      post-graduation. Participants stated that they applied to programs in the U.S.
      because there is wide transferability of qualifications across the world, and
      there is limited or no opportunities for masters level genetic counseling
      training in their home country. Most participants who had applied for jobs in the
      U.S. experienced difficulties regarding unfamiliarity of human resources (HR)
      departments and Border Control Officers with international genetic counselors
      (GCs) and their visa requirements. The results suggest that currently there are
      insufficient job resources tailored to international genetic counselors, and an
      inadequate availability of peer support. The results also speak to the need to
      develop resources for prospective international students and for international
      GCs seeking jobs, and establishment of a peer support network. These resources
      may also provide assistance to genetic counseling training programs and employers
      to address the challenges faced by international genetic counselors.

PMID- 27029194
TI  - Perceptions of Urologists About the Conversational Elements Leading to Treatment
      Decision-Making Among Newly Diagnosed Prostate Cancer Patients.
AB  - Widespread adoption and use of the practice of shared decision-making among
      health-care providers, especially urologists, has been limited. This study
      explores urologists' perceptions about their conversational practices leading to
      decision-making by newly diagnosed prostate cancer patients facing treatment.
      Semi-structured, in-depth interviews were conducted with 12 community and
      academic urologists practicing in the St. Louis, MO, region. Data were analyzed
      using a consensus coding approach. Urologists reported spending 30-60 min with
      newly diagnosed prostate cancer patients when discussing treatment options. They
      frequently encouraged family members' involvement in discussions about treatment,
      especially patients' spouses and children. Participants perceived these
      conversations to be difficult given the emotional burden associated with a cancer
      diagnosis, and encouraged patients to postpone their decisions or to get a second
      opinion before finalizing their treatment of choice. Initial discussions included
      a presentation of treatment options relevant to the patient's condition, side
      effects, outcome probabilities, and next steps. Urologists seldom used statistics
      while talking about treatment outcome probabilities and preferred to explain
      outcomes in terms of the patient's practical, emotional, and social experiences.
      Their styles to elicit the patient's preferences ranged from explicitly asking
      questions to making assumptions based on clinical experience and subtle patient
      cues. In conclusion, urologists' routine conversations included most elements of
      shared decision-making. However, shared decision-making required urologists to
      have nuanced discussions and be skilled in elicitation methods and risk
      discussions which requires further training. Further research is required to
      explore roles of family and clinical staff as participants in this process.

PMID- 27029196
TI  - [Mathematical analysis of the influences of femoral and tibial bone cuts on the
      dynamic alignment in total knee arthroplasty].
AB  - OBJECTIVE: To investigate the influences of the distal femoral cut, the anterior
      and posterior femoral cuts, the proximal tibial cut on the dynamic alignment of
      the lower extremity in total knee arthroplasty. METHODS: Based on the three
      dimensional geometric model, imitating the flexion movement of the knee without
      axial rotation after total knee arthroplasty, the influence of each of the three
      bone cuts on the dynamic alignment was analyzed with the assumption of standard
      bone cuts of the other two and equality of the medial and lateral soft tissue
      balancing. The dynamic alignment was defined as the angle between the mechanical
      axis of the tibia and the sagittal plane of the body when the knee was in any
      angle of flexion. With two of the three major bone cuts standard, the track of
      the tibial movement was established when the other one bone cut deviated from the
      ideal section of angle A. Based on the principle of geometry, the mathematical
      formula were established to present the influences of three bone cuts on the
      dynamic alignment of the lower extremity. RESULTS: All of the three kinds of bone
      cuts in total knee arthroplasty influenced the dynamic alignment of the lower
      extremity not just in one static position, but during the whole range of motion.
      At the theta angle of knee flexion, the alignment of the lower extremity was
      arcsin(costhetasinA) when the varus/valgus femoral component alignment was A; the
      alignment of the lower extremity was arcsin(sinthetasinA) when the rotational
      femoral component alignment was A; the alignment of the lower extremity was A
      when the varus/valgus tibial component alignment was A. CONCLUSION: The
      influences of the distal femoral cut, the anterior and posterior femoral cuts,
      the proximal tibial cut on the dynamic alignment of the lower extremity in total
      knee arthroplasty are dynamically changed during the flexion movement of the
      knee.

PMID- 27029195
TI  - Neuroanatomical features in soldiers with post-traumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD), an anxiety disorder that can
      develop after exposure to psychological trauma, impacts up to 20 % of soldiers
      returning from combat-related deployment. Advanced neuroimaging holds diagnostic
      and prognostic potential for furthering our understanding of its etiology.
      Previous imaging studies on combat-related PTSD have focused on selected
      structures, such as the hippocampi and cortex, but none conducted a comprehensive
      examination of both the cerebrum and cerebellum. The present study provides a
      complete analysis of cortical, subcortical, and cerebellar anatomy in a single
      cohort. Forty-seven magnetic resonance images (MRIs) were collected from 24
      soldiers with PTSD and 23 Control soldiers. Each image was segmented into 78
      cortical brain regions and 81,924 vertices using the corticometric iterative
      vertex based estimation of thickness algorithm, allowing for both a region-based
      and a vertex-based cortical analysis, respectively. Subcortical volumetric
      analyses of the hippocampi, cerebellum, thalamus, globus pallidus, caudate,
      putamen, and many sub-regions were conducted following their segmentation using
      Multiple Automatically Generated Templates Brain algorithm. RESULTS: Participants
      with PTSD were found to have reduced cortical thickness, primarily in the frontal
      and temporal lobes, with no preference for laterality. The region-based analyses
      further revealed localized thinning as well as thickening in several sub-regions.
      These results were accompanied by decreased volumes of the caudate and right
      hippocampus, as computed relative to total cerebral volume. Enlargement in
      several cerebellar lobules (relative to total cerebellar volume) was also
      observed in the PTSD group. CONCLUSIONS: These data highlight the distributed
      structural differences between soldiers with and without PTSD, and emphasize the
      diagnostic potential of high-resolution MRI.

PMID- 27029197
TI  - [Long-term results of the Scorpio posterior-stabilized total knee arthroplasty].
AB  - OBJECTIVE: To evaluate long-term result of Scorpio posterior-stabilized total
      knee arthroplasty. METHODS: There were 160 patients (240 knees) underwent Scorpio
      posterior-stabilized total knee arthroplasty between December 1998 and December
      2000, which were performed by the same surgeon. Patients were followed up from
      June 2013 to December 2013. Knee Society Scoring (KSS), Hospital for Special
      Surgery (HSS) patellofemoral scoring, standard weight-bearing anteroposterior and
      patellar tangential radiographs were assessed. Satisfaction of outcome was
      requested. Alignment of components and presence of radiolucent lines were
      assessed by the radiographic scoring system of knee society. Paired t-test was
      used compared to the data between preoperation and the time of last follow-up.
      RESULTS: Ninety-five patients (141 knees) (59.4%) were followed up. Average
      follow-up duration was 13.3 years (range 12 to 15 years). Eight knees were
      revised due to periprosthetic infection (4 knees), aseptic loosening of tibial
      tray (3 knees) and wear-out of polyethylene insert (1 knee). Compared with
      preoperative ones, KSS knee score, KSS functional score and range of motion
      improved significantly (pre-operation: 26+/-16, 34+/-18, 87 degrees +/-25 degrees
      ; follow-up time: 93+/-8, 78+/-27, 114 degrees +/-22 degrees ) (t=45.55, 15.60,
      13.03, all P<0.01). In terms of KSS knee score and HSS patellofemoral score, 106
      knees were rated as excellence respectively. Ninety-five knees had satisfaction
      with outcome for maximum. The presences of radiolucent lines occurred around 5
      femoral and 11 tibial components with range less than 2 mm. The survival rate at
      10 years was 94.5% with revision for any reason as the end point. CONCLUSION: The
      long-term study indicates that Scorpio posterior-stabilized knee system shows
      favorable clinical and radiological results.

PMID- 27029198
TI  - [Comparison and estimation of different diagnostic methods in detecting the
      presence of periprosthetic joint infection].
AB  - OBJECTIVE: To compare and estimate the diagnostic value and characteristic of
      different diagnostic methods (blood laboratory test, histological analysis,
      synovial fluid cytological test and microbiological examination) in detecting the
      presence of periprosthetic joint infection. METHODS: Data of 52 patients
      underwent hip or knee joint revision in Peking University People's Hospital
      Arthritis Clinic and Research Center between July 2013 and March 2015 were
      analyzed retrospectively. For each patient, results of blood laboratory
      tests(peripheral-blood white blood cell, C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), interleukin-6 (IL-6) and high-sensitivity C-reactive
      protein (Hs-CRP)), histological analysis, synovial fluid white cell count (SWCC),
      microbiological examinations (synovial fluid, tissue and prosthetic joint
      sonication fluid) were collected. Data were analyzed by t-test, independent
      sample median test or chi(2) test, respectively. Sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy for each method
      were calculated and compared by receiver operating characteristic curve. RESULTS:
      There were 30 female and 22 male patients. Twenty-one patients (40.4%) were
      diagnosed as PJI. The levels of CRP, ESR, IL-6 and Hs-CRP in patients with PJI
      were higher than that in aseptic failure patients (Z=23.084, 13.499, 5.796,
      17.045, all P<0.05). The sensitivities of CRP, ESR, IL-6 and Hs-CRP were 90.5%,
      81.0%, 95.0% and 90.0%. The sensitivities of histological analysis and SWCC were
      55.0% and 70.6%, while they had high specificity as 89.7% and 85.7%. The
      sensitivity of sonication fluid culture was 90.0%, which was higher than that of
      tissue culture (71.4%) and synovial fluid culture (65.0%) (chi(2) = 5.333, 6.400,
      all P<0.05). CONCLUSIONS: The tests of CRP, ESR, IL-6 and Hs-CRP have good value
      in detecting PJI preoperatively. Histological analysis and SWCC have high
      specificity, which could help to exclude PJI. Sonication fluid culture has a
      higher sensitivity than tissue culture and synovial fluid culture.

PMID- 27029199
TI  - [The impact of perioperative function exercises on hidden blood loss in elderly
      patients with total hip replacement].
AB  - OBJECTIVE: To investigate the effects of initiative and passive perioperative
      function exercises on hidden blood loss (HBL). METHODS: Two hundreds and thirty
      elderly patients with hip fractures aging from 67 to 87 years (average age of
      73.6 years) who underwent total hip replacement were included. By the intensity
      and the manner of perioperative function exercises, patients were divided into
      four groups: little initiative function exercises group (group A, n=51), little
      initiative and passive function exercises group (group B, n=54), normal
      initiative function exercises group (group C, n=65), normal initiative and
      passive function exercises group (group D, n=60). The true total blood loss, HBL
      and their proportion on the original blood volume and total blood loss was
      calculated depending on height, weight, intra-operative blood loss, post
      operative blood loss, pre- and post-operative hematocrit, and blood transfused.
      According to the proportion of mean HBL on total blood loss, patients were
      divided into low HBL group and high HBL group. The data were analyzed by t test.
      RESULTS: The mean HBL was 517 ml, 41.9% of the total blood loss. Thereinto, the
      mean HBL was 695 ml in group A, 49.3% of the total blood loss, the prevalence of
      high HBL was 66.7% (34/51); the mean HBL was 625 ml in group B, 46.9% of the
      total blood loss, the prevalence of high HBL was 59.3% (32/54); the mean HBL was
      446 ml in group C, 38.4% of the total blood loss, the prevalence of high HBL was
      30.8% (20/65); the mean HBL was 346 ml in group D, 32.3% of the total blood loss,
      the prevalence of high HBL was 20.0% (12/60). Mean HBL, mean HBL/total blood
      loss, prevalence of high HBL were lower in group C than that in group A and group
      B (all P<0.05); and were lower in group D than that in group C (all P<0.05). The
      prevalence was 57.4% (132 cases) in low HBL group, and 42.6% (98 cases) in high
      HBL. The proportion of little initiative function exercises patients in high HBL
      group was obviously higher than that in low HBL group (P<0.05). CONCLUSIONS: The
      intensity and the manner of perioperative function exercises are strongly
      associated with the HBL in elderly patients with total hip replacement. The
      initiative combined with the passive function exercises could be effectively
      prevent and reduce the incidence of high HBL.

PMID- 27029200
TI  - [Three dimensional reconstruction and measurement of the proximal femur in adult
      developmental dysplasia of the hip].
AB  - OBJECTIVE: To investigate characteristics and the differences of the anatomical
      parameters of the proximal femur of the developmental dysplasia of the hip (DDH).
      METHODS: A total of 38 patients(47 hips) diagnosed as DDH with CT scan data and
      the pelvis radiograph from January 2012 to December 2014 in China-Japan Union
      Hospital of Jilin University were retrospectively analyzed. All the hips were
      divided into 3 groups according to Crowe classification method. Thirty normal
      hips were selected as controls who admitted at the same time. CT data of the
      patients were imported into Mimics 17.0. The three-dimensional models of the
      proximal femur were then reconstructed, and the following parameters were
      measured: neck-shaft angle, neck length, offset, height of the centre of femoral
      head, height of the isthmus, height of greater trochanter, the medullary canal
      diameter of isthmus (Di), the medullary canal diameter 10 mm above the apex of
      the lesser trochanter (DT+ 10), the medullary canal diameter 20 mm below the apex
      of the lesser trochanter (DT-20), and then DT+ 10/Di, DT-20/Di and DT+ 10/DT-20
      were calculated.Variance discrepancy analysis was used to compare the difference
      among the four groups, and LSD method was used to compare the difference between
      either two groups. RESULTS: The parameters of neck-shaft angle of DDH with Crowe
      I, Crowe II-III, Crowe IV and the control group were (131.8 degrees +/-7.1
      degrees ), (131.7 degrees +/-6.5 degrees ), (122.8 degrees +/-11.4 degrees ) and
      (131.8 degrees +/-5.9 degrees ), respectively; the parameters of neck-shaft angle
      of DDH with Crowe IV was smaller than that of DDH with Crowe I, Crowe II-III and
      control group (all P<0.05). The parameters of the neck length of DDH with Crowe
      IV ((44.6+/-6.6) mm) was smaller than that of DDH with Crowe I ((48.6+/-6.7) mm),
      Crowe II-III ((50.4+/-4.7) mm) (all P<0.05). There is no statistic difference in
      the offset among the groups (F=2.392, P>0.05). The parameters of the height of
      greater trochanter of DDH with Crowe IV ((12.1+/-6.1) mm) was bigger than that of
      DDH with Crowe I ((8.9+/-7.2) mm), Crowe II-III ((7.5+/-3.3) mm) and control
      group ((6.1+/-3.9) mm) (all P<0.05). The parameters of the height of the centre
      of femoral head of DDH with Crowe I, Crowe II-III, Crowe IV were (39.6+/-6.5) mm,
      (39.1+/-4.2) mm, (38.8+/-8.6) mm, which were smaller than that of the control
      group ((46.5+/-6.2) mm) (all P<0.05). The parameters of Di of DDH with Crowe I,
      Crowe II-III, Crowe IV and the control group were (9.9+/-2.2) mm, (8.3+/-1.8) mm,
      (8.7+/-1.7) mm and (10.1+/-1.4) mm; the parameters of Di of DDH with Crowe II-III
      and Crowe IV were smaller than that of the control group (all P<0.05). The
      parameters of DT+ 10 ((17.2+/-5.3) mm) and DT-20 ((12.2+/-3.0) mm) of DDH with
      Crowe IV were smaller than that of DDH with Crowe I ((25.2+/-3.4) mm, (17.1+/
      2.3) mm) and Crowe II-III ((21.9+/-4.2) mm, (16.3+/-3.2) mm) (all P<0.05). The
      parameter of the height of the isthmus of DDH with Crowe IV ((94.1+/-19.7) mm)
      was smaller than that of DDH with Crowe I ((106.2+/-13.8) mm), Crowe II-III
      ((108.8+/-10.5) mm) and control group ((116.5+/-10.6) mm), respectively (P=0.010,
      0.008, 0.000). The parameters of DT+ 10/Di (2.0+/-0.4) and DT-20/Di (1.4+/-0.2)
      of DDH with Crowe IV were smaller than that of DDH with Crowe I (2.6+/-0.5, 1.8+/
      0.3), Crowe II-III (2.7+/-0.60, 1.9+/-0.3) (all P<0.05). CONCLUSIONS: Comparing
      to DDH with Crowe I-III and control group, DDH with Crowe IV has a dramatic
      change in the intramedullary and extramedullary parameters. The isthmus and the
      great trochanter are higher and there is apparent narrowing of the medullary
      canal around the level of the lesser trochanter.

PMID- 27029201
TI  - [Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience
      from China].
AB  - OBJECTIVE: To explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX)
      regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and
      metastatic pancreatic cancer(MPC). METHODS: Between April 2014 and October 2015,
      35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen
      (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of
      5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang
      University School of Medicine. The primary end point was progression free
      survival. The second end points were overall survival, objective response rate,
      adverse effects, surgical resection rate for LAPC. RESULTS: Among 35 patients, 6
      patients (17.1%) who dropped out and received less than 2 cycles were excluded
      for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4
      adverse effects. No patients ceased treatment due to adverse effects. The 29
      patients received 5 (2-13) cycles were evaluated by efficacy and found partial
      remission in 16 cases, stable disease in 10 cases, progression disease in 3
      cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery
      after neoadjuvant treatment without perioperative complication and death, and 6
      patients accepted R0 resection. CONCLUSIONS: The mFOLFIRINOX regimen used in the
      study is well-tolerated in Chinese population with high treatment efficacy on
      patients with LAPC and MPC. Further investigation of efficacy and adverse effects
      on more advanced pancreatic cancer patients is necessary.

PMID- 27029202
TI  - [Surgical treatment of total anomalous pulmonary venous connection under 6 months
      of age].
AB  - OBJECTIVE: To discuss the experience of surgical treatment of total anomalous
      pulmonary venous connection (TAPVC) in infants. METHODS: The clinic data of 84
      cases with TAPVC under 6 months of age underwent surgical treatment at Department
      of Cardiac Surgery, Guangzhou Women and Children's Medical Center from January
      2012 to October 2015 were analyzed retrospectively. There were 58 male and 26
      female patients. The patients were aged 1 days to 6 months with a mean of (2.4+/
      2.2) months at surgery, including 22 newborns. Body weight was 1.8 to 6.8 kg with
      a mean of (4.3+/-1.2) kg. There were 24 cases of intracardiac type, 46 cases of
      supracardiac type, 10 cases of infracardiac type and 4 cases of mixed type. There
      were 26 cases received emergent operation. There were 14 cases used Sutureless
      technique in operations and 46 cases used conventional methods in the no
      intracardiac type cases, and 2 cases enlarged the anastomsis with autologous
      pericardium. According to the condition, corrective surgeries of other anomalies
      were performed in the meantime, including 3 Warden operations (right side), 3
      bilateral bidirectional Gleen operation, 2 correction of unroofed coronary sinus
      syndrome, 1 coarctation of aorta correction with deep hypothermic circulation
      arrest, and 1 repair of ventricular septal defect. RESULTS: The ratio of newborn
      was higher in Sutureless technique group than in conventional methods group (7/14
      vs. 32.6%, chi(2)=4.927, P=0.043), and mean age was less ((1.8+/-0.4) months vs.
      (2.4+/-2.2) months, F=4.257, P=0.042), but there were no difference in body
      weight, cardiopulmonary bypass time and aorta clamped time between the two
      groups. Followed up for 1 to 46 months, 10 cases (11.9%) died overall and the
      mortality of intracardiac (3/10) and mixed (2/4) type were much higher than in
      intracardiac (4.2%) and supracardiac (13.0%) type. The mortality were no
      difference between newborn and infants, or whether emergent operation, or
      Sutureless technique and conventional methods. The maximal pulmonary venous flow
      velocity was abnormal speed-up >1.8 m/s at 1 week and 1 to 3 months post
      operation mostly. CONCLUSIONS: The mortality of TAPVC was differed by different
      types. Intrinsic pulmonary vein stenosis maybe the main cause of mortality. The
      high quality of anastomsis could reduce the operative mortality.

PMID- 27029203
TI  - [Application of lymphography in the location and treatment decision of chyle
      leakage: an analysis of 177 cases].
AB  - OBJECTIVE: To identify the value of lymphography in the location and treatment
      decision of chyle leakage. METHODS: The clinic data of 177 patients suffered from
      chyle leakage admitted in 6 medical centers in Shanghai from February 1998 to
      December 2014 was analyzed retrospectively. There were 94 male and 83 female
      patients aging from 9 to 84 years with a mean of 49 years, including 128 cases of
      chyluria, 34 cases of primary chylothorax and 15 cases of other chyle leakage.
      All patients had failed to conservative treatment more than 2 weeks. Pedal
      lymphography was performed in every patient to investigate the site and range of
      chyle leakage. Effect of surgical or conservative management was compared
      according to the different results of lymphography. RESULTS: No serious
      complication was noticed. For all 177 patients, lymphography showed localized
      lymphatic diseases in 148 cases (83.6%), including 125 cases of lymphatic renal
      pelvic leaks, 14 cases of unilateral identified leak within thorax and 9 cases of
      chyle leakage in neck, heart, abdomen or scrotum. Among these patients, surgical
      treatment cured 129 and improved 3 patients but failed in 2 patients, while the
      remaining 14 cases had their leaks decreased after lymphography and cured by
      conservative management. For those 15 patients having disseminated lymphatic
      diseases or 14 with no abnormality under lymphography, surgery only cured 2 and
      improved 1 patient but failed in 8 patients (with 3 death), whereas continuous
      conservative treatment cured 11 patients, improved 5 patients but only failed in
      2 patients (with one death). For localized leakage, surgical treatment showed
      better efficacy (98.5% vs. 3/11), whereas conservative treatment had
      significantly higher successful rate than surgical interventions in patients with
      disseminated lymphatic diseases or no abnormality under lymphography (16/18 vs.
      3/11). CONCLUSIONS: Lymphography could identify the location and range of
      complicate chyle leakage failed to primary conservative management. Patients with
      disseminated lymphatic diseases or no abnormality under lymphography would be
      better managed by continuous non-operative treatment partly due to therapeutic
      effect of lymphography, while surgical intervention could be a good option for
      patients having localized lymphatic etiology.

PMID- 27029204
TI  - [The construction of a tissue-engineered tendon mimicking the transitional
      architecture at the ligament-bone interface in rabbit].
AB  - OBJECTIVE: To investigate a method that constructing a tissue-engineered tendon
      with a continuous and heterogeneous transition region. METHODS: Fibroblasts
      derived from rabbit epithelial tissue were cultured in vitro and collagen gel was
      prepared. The experimental groups were scaffold only group, fibroblasts+
      chondrocytes group (Fb+ CC group), fibroblasts+ osteoblasts group (Fb+ OB group),
      fibroblasts+ chondrocytes+ osteoblasts group (Fb+ CC+ OB group). Heterogeneous
      cell populations(fibroblasts, chondrocytes and osteoblasts) with collagen gel
      were seeded within three predesigned specific regions (fibrogenesis,
      chondrogenesis, and osteogenesis) of decellularized rabbit achilles tendons to
      fabricate a stratified scaffold containing three biofunctional regions supporting
      fibrogenesis, chondrogenesis, and osteogenesis. The tests of morphology,
      architecture and cytocompatibility of the scaffolds were performed. Gradient
      tissue-specific matrix formation was analysed within the predesignated regions
      via histological staining and immunofluorescence assays. RESULTS: The HE staining
      and scanning electron microscopy analysis demonstrated that no major cell
      fragments or nuclear material was evident, and increased intra-fascicular and
      inter-fascicular spaces were found, the cytocompatibility of the scaffolds showed
      that the numbers of viable cells on the scaffold surfaces increase steadily, no
      significant differences were found between the scaffold only containing ordinary
      culture medium and scaffold containing gel groups. Histological staining and
      immunofluorescence assays demonstrated that the cartilage-related markers (GAG,
      COL2A1) were found only in the chondrogenesis region, but bone-related proteins
      only in the osteogenesis region of bone tunnel, and fibrosis was remarkable for
      the fibrogenesis region in the joint cavity. The transitional architecture with
      ligament-fibrocartilage-bone was constructed in the ligament-bone tunnel
      interface. CONCLUSIONS: A transitional interface (fiber-fiberocartilage-bone)
      could be replicated in a decellularized tendon through stratified tissue
      integration in vitro. The cell-tendon complex offers the advantages of a multi
      tissue transition involving controlled cellular interactions and matrix
      heterogeneity.

PMID- 27029205
TI  - [Mechanism of vacuum sealing drainage therapy attenuating ischemia-reperfusion
      injury of skeletal muscle in rabbit].
AB  - OBJECTIVE: To investigate the mechanism of how vacuum sealing drainage (VSD)
      ameliorating ischemia reperfusion (I/R) injury in skeletal muscle I/R model.
      METHODS: Thirty New Zealand white rabbits were divided into three groups: control
      (sham operation) group, I/R group, VSD+ I/R group.The ischemia of the left hind
      limb of the animal was induced by clamping the common femoral artery and vein.
      After 4 hours of ischemia, the clamp was removed and the hind limp underwent 6
      hours reperfusion. VSD treated animals received the treatment at the beginning of
      reperfusion. The concentrations of myeloperoxidase (MPO), malondialdehyde (MDA),
      superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in muscular
      tissues were assayed. HE stained pathological section was used to evaluate the
      degree of edema of muscular tissues, and the immunohistochemistry was used to
      detect the percentage of positive cells expressing high mobility group protein B1
      (HMGB1). Q-RT-PCR and Western Blot were used to detect the mRNA levels and
      protein expression of HMGB1 in myocyte respectively. The experimental data was
      tested using variance analysis. RESULTS: The levels of inflammatory factors and
      antioxidant factors in muscular tissues were significantly different in the I/R
      group compared to the VSD group and control group (the levels of MPO in I/R
      group, I/R+ VSD group and control group were 0.91+/-0.22, 0.53+/-0.08, 0.31+/
      0.10, respectively, F=26.48, P=0.000; MDA were 2.04+/-0.92, 1.65+/-1.02, 1.01+/
      0.12, F=4.250, P=0.040; SOD were 35.97+/-9.23, 55.99+/-18.97, 61.83+/-14.91,
      F=5.240, P=0.020; CAT were 31.42+/-16.27, 48.50+/-17.86, 75.95+/-13.09, F=9.720,
      P=0.002; GSH were 1.48+/-0.90, 3.54+/-1.88, 3.84+/-2.08, F=5.240, P=0.020). HE
      staining showed an increased intercellular space ratio in the I/R group (F=16.47,
      P<0.05). Immunohistochemistry staining showed that percentage of HMGB1 positive
      myocytes in control, I/R and I/R+ VSD group are 1.94%, 18.63% and 61.36%,
      respectively. There was significant difference among groups (F=853.886, P<0.01).
      A significantly inhibited HMGB1 expression by VSD therapy was also validated by
      the results of Q-RT-PCR (F=50.653, P<0.01) and Western blot (F=963.489, P<0.01).
      CONCLUSION: The results from the present research suggest that VSD may attenuate
      skeletal muscles I/R injury by increasing the cellular antioxidative stress
      reaction and inhibiting the reactive oxygen species as well as the inflammatory
      mediators.

PMID- 27029206
TI  - [The role of infrapatellar fat pad in knee osteoarthritis and total knee
      arthroplasty].
AB  - Knee osteoarthritis (KOA) is the most common knee joint disease. Although KOA
      belongs to a disease of degeneration of knee joint cartilage, its pathology
      involves cartilage, subchondral bone, meniscus, synovial membrane, articular
      capsule and other joint tissue. The infrapatellar fat pad (IPFP), an
      intracapsular but extrasynovial structure, has some special characteristics of
      endocrine metabolism, then it has double roles in the development of KOA, but its
      protective effect is much more than harmful effect. Considering protective roles
      of IPFP in KOA and some serious complications after IPFP resection, the surgeon
      shall protect IPFP as far as possible if total knee arthroplasty surgical field
      is good. If it is necessary to improve the surgical field, its fibrotic tissue
      even all part can be removed.

PMID- 27029207
TI  - [Advances in congenital vertebral malformation caused by genomic copy number
      variation].
AB  - Congenital vertebral malformation (CVM) is a congenital vertebral structural
      deformity caused by abnormal somitogenesis during embryonic development, of which
      the reason lies in gene mutation or abnormal regulation of the genes that
      coordinate somitogenesis during embryonic period. ICVAS had proposed a new
      classification algorithm for CVM, which facilitated exploration for its genetic
      etiology. Genomic Copy Number Variation (CNV) is a kind of DNA mutation, which is
      important for human evolution, phenotype polymorphism and diseases. Series of
      advances have been made on genetic causes of CVM, especially on CVM caused by
      CNV. CNVs of chromosome 16p11.2, 10q24.31, 17p11.2, 20p11, 22q11.2 and a few
      other regions are associated with CVM, indicating that gene dosage may play
      important roles in the development of the spinal cord.

PMID- 27029208
TI  - [The application progress of human urine derived stem cells in bone tissue
      engineering].
AB  - The research of bone tissue engineering bases on three basic directions of seed
      cells, scaffold materials and growth information. Stem cells have been widely
      studied as seed cells. Human urine-derived stem cell (hUSC) is extracted from
      urine and described to be adhesion growth, cloning, expression of the majority of
      mesenchymal stem cell markers and peripheral cell markers, multi-potential and no
      tumor but stable karyotype with passaging many times. Some researches proposed
      that hUSC might be a new source of seed cells in tissue engineering because of
      their invasive and convenient obtention, stable culture and multiple
      differentiation potential.

PMID- 27029209
TI  - Molecular Details of Acetate Binding to a New Diamine Receptor by NMR and FT-IR
      Analyses.
AB  - Acetate anion plays an important role in several biochemical functions such as
      enzyme reaction, antibody response, and action of receptor molecules. This
      investigation reports the synthesis and molecular details of a unique receptor, 2
      amino-N-(2-amino-benzyl)-benzamide (R) that senses selectively acetate via
      simultaneous involvement of one aromatic amine group and an amide proton of the
      receptor molecule. Solution-state NMR, steady-state fluorescence, and FT-IR
      examinations established that the acetate anion binds to the receptor with 1:1
      ratio with high specificity. The binding was stabilized by two H-bond formations
      between the oxygen atoms of acetate anion and two H atoms, one from amide group
      and the other from the amine group of the receptor. The binding interaction
      caused significant changes in the chemical shift of the receptor protons, and the
      evaluated affinity constant, from the NMR measurements, was found to be 1.87 *
      10(4) M(-1). Density functional theory (DFT) analysis further showed a
      significant rotation of one of the two aromatic rings leading to formation of a
      10-member ring involving the acetate anion, amide proton, and the one amine group
      attached to aromatic ring. The H-bond patterns observed in the crystal structure
      were significantly changed due to complex formation. However, the changes in the
      geometrical arrangement in the complex caused a small but significant increase of
      the fluorescence emission. Acetate geometry and unique positioning of the amide
      and amine groups of the receptor render the recognition feasible, and DFT
      analysis estimated ~30 kJ M(-1) stabilization due to 1:1 complexation. Such
      positioning and geometrical arrangement may make the receptor very specific to
      bind acetate anion, and as such R became a very relevant molecule in detection
      and function of the acetate anion present in complex biochemical systems. 

PMID- 27029210
TI  - Margaret McCartney: Privacy is not secrecy.

PMID- 27029211
TI  - Translation and cross-cultural adaptation of a standardized international
      questionnaire on use of alternative and complementary medicine (I-CAM - Q) for
      Argentina.
AB  - BACKGROUND: The widespread and growing use of alternative and complementary
      medicine (CAM) worldwide has been thoroughly described. In Argentina the limited
      information on the use of CAM has been reported between 40 and 55 %. However, the
      rate of use is extremely variable worldwide. For this purpose the international
      questionnaire on the use of complementary and alternative medicines (I-CAM - Q),
      was developed. The implementation of a translated and cross-culturally adapted
      version of the questionnaire would allow for a reliable and standardized
      evaluation of the rate of use of CAM in Argentina. It would be a great step
      towards improving what we know about the healing habits of our population.
      METHODS: The forward and back-translation method was used. Four translators were
      involved. A committee was commissioned to reconcile the different versions. The
      process of cross-cultural adaptation was made by consulting 17 alternative and
      complementary medicine experts using the DELPHI method. The retrieved
      questionnaire was evaluated in 18 patients sampled by convenience (9 men,
      different educational and self-reported health levels). The interviews consisted
      of three parts: an initial demographics questionnaire; the administration of the
      I-CAM-Q and finally the cognitive interview, which included reviewing the
      questionnaire and reexamining questions that generated doubts during the
      interview. The comprehension of the questions was also evaluated. As a last step,
      using the information obtained from the interviews, the final version of the
      questionnaire was drafted. RESULTS AND CONCLUSION: The questionnaire seems to
      have been accepted by most patients during the interviews. Conflictive elements
      that emerged did not seem to have an impact on its administration. The
      flexibility of the questionnaire allowed to add professionals and practices which
      contributed to a more accurate local adaptation. Further research should focus on
      assessing the questionnaire's psychometric performance and validity, which so far
      has not been done.

PMID- 27029212
TI  - Long-Term Citalopram Treatment Alters the Stress Responses of the Cortical
      Dopamine and Noradrenaline Systems: the Role of Cortical 5-HT1A Receptors.
AB  - BACKGROUND: Cortical dopamine and noradrenaline are involved in the stress
      response. Citalopram, a selective serotonin reuptake inhibitor, has direct and
      indirect effects on the serotonergic system. Furthermore, long-term treatment
      with citalopram affects the dopamine and noradrenaline systems, which could
      contribute to the therapeutic action of antidepressants. METHODS: The effects of
      long-term treatment with citalopram on the responses of the dopamine and
      noradrenaline systems in the rat prefrontal cortex to acute handling stress were
      evaluated using in vivo microdialysis. RESULTS: Acute handling stress increased
      dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and
      noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor
      agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into
      the prefrontal cortex. The dopamine response was abolished by long-term treatment
      with citalopram, and the abolished dopamine response was reversed by local
      infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2
      methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the
      prefrontal cortex. On the other hand, long-term treatment with citalopram reduced
      the basal noradrenaline levels (approximately 40% of the controls), but not the
      basal dopamine levels. The noradrenaline response was maintained despite the low
      basal noradrenaline levels. Signaling from the 5-HT1A receptors and alpha2
      adrenoceptors was not involved in the decrease in the basal noradrenaline levels
      but partially affected the noradrenaline response. CONCLUSIONS: Chronic
      citalopram treatment differentially suppresses the dopamine and noradrenaline
      systems in the prefrontal cortex, and the dopamine stress response was
      preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings
      provide insight into how antidepressants modulate the dopamine and noradrenaline
      systems to overcome acute stress.

PMID- 27029213
TI  - Genetic diversity analysis of two commercial breeds of pigs using genomic and
      pedigree data.
AB  - BACKGROUND: Genetic improvement in livestock populations can be achieved without
      significantly affecting genetic diversity if mating systems and selection
      decisions take genetic relationships among individuals into consideration. The
      objective of this study was to examine the genetic diversity of two commercial
      breeds of pigs. Genotypes from 1168 Landrace (LA) and 1094 Large White (LW)
      animals from a commercial breeding program in Brazil were obtained using the
      Illumina PorcineSNP60 Beadchip. Inbreeding estimates based on pedigree (F x) and
      genomic information using runs of homozygosity (F ROH) and the single nucleotide
      polymorphisms (SNP) by SNP inbreeding coefficient (F SNP) were obtained. Linkage
      disequilibrium (LD), correlation of linkage phase (r) and effective population
      size (N e ) were also estimated. RESULTS: Estimates of inbreeding obtained with
      pedigree information were lower than those obtained with genomic data in both
      breeds. We observed that the extent of LD was slightly larger at shorter
      distances between SNPs in the LW population than in the LA population, which
      indicates that the LW population was derived from a smaller N e . Estimates of N
      e based on genomic data were equal to 53 and 40 for the current populations of LA
      and LW, respectively. The correlation of linkage phase between the two breeds was
      equal to 0.77 at distances up to 50 kb, which suggests that genome-wide
      association and selection should be performed within breed. Although selection
      intensities have been stronger in the LA breed than in the LW breed, levels of
      genomic and pedigree inbreeding were lower for the LA than for the LW breed.
      CONCLUSIONS: The use of genomic data to evaluate population diversity in
      livestock animals can provide new and more precise insights about the effects of
      intense selection for production traits. Resulting information and knowledge can
      be used to effectively increase response to selection by appropriately managing
      the rate of inbreeding, minimizing negative effects of inbreeding depression and
      therefore maintaining desirable levels of genetic diversity.

PMID- 27029214
TI  - Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8
      secretion through activation of Toll-like receptor 8.
AB  - STUDY QUESTION: What is the role of microRNAs (miRs) in antiphospholipid antibody
      (aPL)-induced trophoblast inflammation? SUMMARY ANSWER: aPL-induced up-regulation
      of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR
      146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the
      RNA sensor, TLR8. WHAT IS KNOWN ALREADY: Obstetric antiphospholipid syndrome
      (APS) is an autoimmune disorder characterized by circulating aPL and an increased
      risk of pregnancy complications. We previously showed that aPL recognizing beta2
      glycoprotein I (beta2GPI) elicit human first trimester trophoblast secretion of
      IL-8 by activating TLR4. Since some miRs control TLR responses, their regulation
      in trophoblast cells by aPL and functional role in the aPL-mediated inflammatory
      response was investigated. miRs can be released from cells via exosomes, and
      therefore, miR exosome expression was also examined. A panel of miRs was selected
      based on their involvement with TLR signaling: miR-9; miR-146a-5p and its isomiR,
      miR-146a-3p; miR-155, miR-210; and Let-7c. Since certain miRs can activate the
      RNA sensor, TLR8, this was also investigated. STUDY DESIGN, SIZE, DURATION: For
      in vitro studies, the human first trimester extravillous trophoblast cell line,
      HTR8 was studied. HTR8 cells transfected to express a TLR8 dominant negative (DN)
      were also used. Plasma was evaluated from pregnant women who have aPL, either
      with or without systemic lupus erythematous (SLE) (n = 39); SLE patients without
      aPL (n = 30); and healthy pregnant controls (n = 20). PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Trophoblast HTR8 wildtype and TLR8-DN cells were incubated with
      or without aPL (mouse anti-human beta2GPI mAb) for 48-72 h. HTR8 cells were also
      treated with or without aPL in the presence and the absence of a TLR4 antagonist
      (lipopolysaccharide from Rhodobacter sphaeroides; LPS-RS), specific miR
      inhibitors or specific miR mimics. miR expression levels in trophoblast cells,
      trophoblast-derived exosomes and exosomes isolated from patient plasma were
      measured by qPCR. Trophoblast IL-8 secretion was measured by ELISA. MAIN RESULTS
      AND THE ROLE OF CHANCE: aPL significantly increased trophoblast cellular and
      exosome expression of miR-146a-5p, miR-146a-3p, miR-155 and miR-210. aPL-induced
      up-regulation of trophoblast miR-146a-5p, miR-146a-3p and miR-210, but not miR
      155, was inhibited by the TLR4 antagonist, LPS-RS. While inhibition or
      overexpression of miR-146a-5p had no effect on aPL-induced trophoblast IL-8
      secretion, miR-146a-3p inhibition significantly reduced this response. aPL
      induced trophoblast IL-8 secretion was inhibited by the presence of the TLR8-DN.
      In the absence of aPL, transfection of trophoblast cells with a miR-146a-3p mimic
      significantly increased IL-8 secretion and this was inhibited by the presence of
      the TLR8-DN. Patients with aPL and adverse pregnancy outcomes (APOs) expressed
      significantly higher levels of circulating miR-146a-3p compared with healthy
      pregnant controls with no pregnancy complications (P < 0.05). LIMITATIONS,
      REASONS FOR CAUTION: While the enrichment of miR-146a-3p in trophoblast-derived
      exosomes support the role of this miR acting in a paracrine or endocrine manner
      through exosome delivery, this has not been demonstrated. However, miR-146a-3p
      may also exert its pro-inflammatory effect intracellularly within the same
      trophoblast cell targeted by aPL. WIDER IMPLICATIONS OF THE FINDINGS: These
      findings provide a novel mechanism of trophoblast inflammation through miRs
      activating RNA-sensing receptors. Furthermore, circulating exosomal-associated
      miR-146a-3p in APS patients may serve clinically as a biomarker for related APOs.
      STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by grants
      from the American Heart Association (#10GRNT3640032 to V.M.A.), the March of
      Dimes Foundation (Gene Discovery and Translational Research Grant #6-FY12-255 to
      V.M.A.), NICHD, NIH (R01HD049446 to V.M.A.), the Gina M. Finzi Memorial Student
      Summer Fellowship from the Lupus Foundation of America (to S.M.G.), and the Yale
      University School of Medicine Medical Student Fellowship (to S.M.G.). The authors
      declare no competing financial interests. TRIAL REGISTRATION NUMBER: N/A.

PMID- 27029215
TI  - beta-TrCP-mediated ubiquitination and degradation of liver-enriched transcription
      factor CREB-H.
AB  - CREB-H is an endoplasmic reticulum-resident bZIP transcription factor which
      critically regulates lipid homeostasis and gluconeogenesis in the liver. CREB-H
      is proteolytically activated by regulated intramembrane proteolysis to generate a
      C-terminally truncated form known as CREB-H-DeltaTC, which translocates to the
      nucleus to activate target gene expression. CREB-H-DeltaTC is a fast turnover
      protein but the mechanism governing its destruction was not well understood. In
      this study, we report on beta-TrCP-dependent ubiquitination and proteasomal
      degradation of CREB-H-DeltaTC. The degradation of CREB-H-DeltaTC was mediated by
      lysine 48-linked polyubiquitination and could be inhibited by proteasome
      inhibitor. CREB-H-DeltaTC physically interacted with beta-TrCP, a substrate
      recognition subunit of the SCF(beta-TrCP) E3 ubiquitin ligase. Forced expression
      of beta-TrCP increased the polyubiquitination and decreased the stability of CREB
      H-DeltaTC, whereas knockdown of beta-TrCP had the opposite effect. An
      evolutionarily conserved sequence, SDSGIS, was identified in CREB-H-DeltaTC,
      which functioned as the beta-TrCP-binding motif. CREB-H-DeltaTC lacking this
      motif was stabilized and resistant to beta-TrCP-induced polyubiquitination. This
      motif was a phosphodegron and its phosphorylation was required for beta-TrCP
      recognition. Furthermore, two inhibitory phosphorylation sites close to the
      phosphodegron were identified. Taken together, our work revealed a new
      intracellular signaling pathway that controls ubiquitination and degradation of
      the active form of CREB-H transcription factor. 

PMID- 27029216
TI  - Shielding of the Geomagnetic Field Alters Actin Assembly and Inhibits Cell
      Motility in Human Neuroblastoma Cells.
AB  - Accumulating evidence has shown that absence of the geomagnetic field (GMF), the
      so-called hypomagnetic field (HMF) environment, alters the biological functions
      in seemingly non-magnetosensitive cells and organisms, which indicates that the
      GMF could be sensed by non-iron-rich and non-photo-sensing cells. The underlying
      mechanisms of the HMF effects on those cells are closely related to their GMF
      sensation but remain poorly understood so far. Previously, we found that the HMF
      represses expressions of genes associated with cell migration and cytoskeleton
      assembly in human neuroblastoma cells (SH-SY5Y cell line). Here, we measured the
      HMF-induced changes on cell morphology, adhesion, motility and actin cytoskeleton
      in SH-SY5Y cells. The HMF inhibited cell adhesion and migration accompanied with
      a reduction in cellular F-actin amount. Moreover, following exposure to the HMF,
      the number of cell processes was reduced and cells were smaller in size and more
      round in shape. Furthermore, disordered kinetics of actin assembly in vitro were
      observed during exposure to the HMF, as evidenced by the presence of granule and
      meshed products. These results indicate that elimination of the GMF affects
      assembly of the motility-related actin cytoskeleton, and suggest that F-actin is
      a target of HMF exposure and probably a mediator of GMF sensation. 

PMID- 27029217
TI  - Auditory and visual information in speech perception: A developmental
      perspective.
AB  - This study investigates the development of audiovisual speech perception from age
      4 to 80, analysing the contribution of modality, context and special features of
      specific language being tested. Data of 77 participants in five age groups is
      presented in the study. Speech stimuli were introduced via auditory, visual and
      audiovisual modalities. Monosyllabic meaningful and nonsense words were included
      in a signal-to-noise ratio of 0 dB. Speech perception accuracy in audiovisual and
      auditory modalities by age resulted in an inverse U-shape, with lowest
      performance at ages 4-5 and 65-80. In the visual modality, a clear difference was
      shown between performance of children (ages 4-5 and 8-9) and adults (age 20 and
      above). The findings of the current study have important implications for
      strategic planning in rehabilitation programmes for child and adult speakers of
      different languages with hearing difficulties. 

PMID- 27029218
TI  - Analysis of Drosophila melanogaster proteome dynamics during embryonic
      development by a combination of label-free proteomics approaches.
AB  - During embryogenesis, organisms undergo considerable cellular remodelling
      requiring the combined action of thousands of proteins. In case of the well
      studied model Drosophila melanogaster, transcriptomic studies, most notably from
      the modENCODE project, have described in detail changes in gene expression at the
      mRNA level across development. Although such data are clearly very useful to
      understand how the genome is regulated during embryogenesis, it is important to
      understand how changes in gene expression are reflected at the level of the
      proteome. In this study, we describe a combination of two quantitative label-free
      approaches, SWATH and data-dependent acquisition, to monitor changes in protein
      expression across a timecourse of D. melanogaster embryonic development. We
      demonstrate that both approaches provide robust and reproducible methods for the
      analysis of proteome changes. In a preliminary analysis of Drosophila
      embryogenesis, we identified several pathways, including the heat-shock response,
      nuclear protein import and energy production that are regulated during embryo
      development. In some cases changes in protein expression mirrored transcript
      levels across development, whereas other proteins showed signatures of post
      transcriptional regulation. Taken together, our pilot study provides a solid
      platform for a more detailed exploration of the embryonic proteome.

PMID- 27029219
TI  - Unexplained spikes in lamotrigine serum concentration: nonlinear elimination?
AB  - OBJECTIVES: The objective of this study was to evaluate possible nonlinear
      lamotrigine (LTG) pharmacokinetics at elevated concentration. LTG is reported to
      have linear kinetics, so that elimination rate is linearly proportional to blood
      concentration and a change in dose is accompanied by a proportionate change in
      serum concentration. We encountered patients in whom LTG serum concentration
      increased dramatically in response to minor or no change in LTG dose. We studied
      this phenomenon in patients with LTG toxicity in one clinic. MATERIALS AND
      METHODS: Using electronic medical records from 1997 to 2014, we identified
      patients who developed clinical LTG toxicity with LTG serum concentrations >20
      mg/l, after tolerating lamotrigine at lower serum concentrations. We reviewed LTG
      dose change and other changes that preceded the episode of toxicity. RESULTS:
      Twenty-two patients had at least one episode of LTG toxicity with levels higher
      than 20 mg/l (of 922 patients with available levels). The peak serum
      concentration varied from 21.1 to 40.3 mg/l (mean 28.7). The increase in level
      was explained in three patients (post-delivery in one, addition of valproate in
      two). In the 18 others, the increase was not explained or it was disproportionate
      to an increase in LTG dose. CONCLUSIONS: Spikes in LTG levels and associated
      clinical toxicity may occur unexpectedly, suggesting that elimination kinetics
      may be nonlinear in some individuals at serum concentrations in the upper range.
      Measurement and close monitoring of LTG levels is warranted for new symptoms that
      could be consistent with lamotrigine toxicity, particularly when the baseline
      serum concentration has been >10 mg/l.

PMID- 27029220
TI  - An Update on Gender Disparities in Coronary Heart Disease Care.
AB  - Coronary heart disease (CHD), traditionally considered a male disease, causes far
      more deaths in women than cancer. The prevalence of CHD is lower in women at any
      age, but with advancing age, this differential decreases. The clinical outcomes
      including myocardial infarction mortality, all-cause mortality, and reinfarction
      rates are also worse in women with cardiovascular diseases (CVD) than in men.
      Yet, women appear to be underdiagnosed and undertreated for coronary heart
      disease. There is still a gap in the knowledge, understanding, and general
      awareness of CHD in women. This review provides updates in gender disparities in
      the management of risk factors, treatments, and outcomes of coronary heart
      disease. 

PMID- 27029221
TI  - Investigation on rifampicin administration from the standpoint of
      pharmacokinetics/pharmacodynamics in a neutropenic murine thigh infection model.
AB  - BACKGROUND: The purpose of this study was to examine the
      pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible
      Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and
      vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection
      model. METHODS: Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA
      [Mu50]) with rifampicin MIC 0.06 to >256 MUg/mL were tested. The efficacy was
      calculated as the change in bacterial density. A maximum effect model was used to
      determine the PK/PD index that best described the dose-response data. RESULTS:
      The area under the curve (AUC)/MIC and maximum concentration of drug in serum
      (Cmax/MIC) were the best correlated with in vivo efficacy (AUC/MIC, R(2) = 0.96;
      Cmax/MIC, R(2) = 0.97) for S. aureus ATCC 25923 strain, and the dose
      fractionation-response study did not show significantly different antimicrobial
      activity (p = 0.10). The AUC/MIC values associated with stasis and 1-log kill for
      the S. aureus ATCC 25923 strain were 386 and 952, respectively. On the other
      hand, no antimicrobial efficacy was observed against two strains (MRSA and VISA)
      with MIC of 128 MUg/mL or more. CONCLUSION: Rifampicin demonstrated concentration
      dependent killing. The AUC/MIC was a predictive PK/PD index.

PMID- 27029222
TI  - The concept of stigma in mental illness as applied to Haitian Americans.
AB  - AIM: To report on the analysis of the concept of the stigma of mental illness
      within the Haitian American community. BACKGROUND: Mental illness is a highly
      stigmatized condition within certain communities making it challenging for
      individuals to seek effective treatment. The consequences of such stigma can have
      lifelong corollaries for the individuals, the families and the communities.
      INTRODUCTION: The concept of stigma is not fully developed in nursing; clarity of
      the concept of stigma of mental illness is still needed in the nursing
      literature. In order to assist patients in accessing mental health services, the
      concept of stigma must first be clarified. METHODS: The method used for this
      concept analysis was that of Walker and Avant. FINDINGS: Five attributes were
      identified, creating the following definition: labelling, stereotype, negative
      attitude, emotional response, and discrimination. The antecedents for stigma of
      mental illness are lack of knowledge about mental illness, emotional state and
      cultural beliefs and values. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The
      origins of stigmatization of mental illness among Haitian Americans need to be
      understood. Mental health illnesses are stigmatized within the Haitian culture,
      which presents as a barrier to accessing help for many Haitian American women
      suffering from mental illness. The defining attributes can be used to develop
      tools to help clinicians identify patients being stigmatized. Once stigma is
      recognized, nurses can develop strategies and policies that can mitigate the
      effects of stigmatization of mental illness among this patient population.
      CONCLUSION: Further research is essential to examine the ways in which this
      concept impacts the Haitian American community, as well as effective strategies
      to help minimize its effects.

PMID- 27029223
TI  - Gamma knife radiosurgery in movement disorders: Indications and limitations.
AB  - Functional radiosurgery has advanced steadily during the past half century since
      the development of the gamma knife technique for treating intractable cancer
      pain. Applications of radiosurgery for intracranial diseases have increased with
      a focus on understanding radiobiology. Currently, the use of gamma knife
      radiosurgery to ablate deep brain structures is not widespread because
      visualization of the functional targets remains difficult despite the increased
      availability of advanced neuroimaging technology. Moreover, most existing reports
      have a small sample size or are retrospective. However, increased experience with
      intraoperative neurophysiological evaluations in radiofrequency thalamotomy and
      deep brain stimulation supports anatomical and neurophysiological approaches to
      the ventralis intermedius nucleus. Two recent prospective studies have promoted
      the clinical application of functional radiosurgery for movement disorders. For
      example, unilateral gamma knife thalamotomy is a potential alternative to
      radiofrequency thalamotomy and deep brain stimulation techniques for intractable
      tremor patients with contraindications for surgery. Despite the promising
      efficacy of gamma knife thalamotomy, however, these studies did not include
      sufficient follow-up to confirm long-term effects. Herein, we review the
      radiobiology literature, various techniques, and the treatment efficacy of gamma
      knife radiosurgery for patients with movement disorders. Future research should
      focus on randomized controlled studies and long-term effects. (c) 2016
      International Parkinson and Movement Disorder Society.

PMID- 27029224
TI  - Sixty seconds on . . . the war on drugs.

PMID- 27029225
TI  - Oxygen depletion recorded in upper waters of the glacial Southern Ocean.
AB  - Oxygen depletion in the upper ocean is commonly associated with poor ventilation
      and storage of respired carbon, potentially linked to atmospheric CO2 levels.
      Iodine to calcium ratios (I/Ca) in recent planktonic foraminifera suggest that
      values less than ~2.5 MUmol mol(-1) indicate the presence of O2-depleted water.
      Here we apply this proxy to estimate past dissolved oxygen concentrations in the
      near surface waters of the currently well-oxygenated Southern Ocean, which played
      a critical role in carbon sequestration during glacial times. A down-core
      planktonic I/Ca record from south of the Antarctic Polar Front (APF) suggests
      that minimum O2 concentrations in the upper ocean fell below 70 MUmol kg(-1)
      during the last two glacial periods, indicating persistent glacial O2 depletion
      at the heart of the carbon engine of the Earth's climate system. These new
      estimates of past ocean oxygenation variability may assist in resolving
      mechanisms responsible for the much-debated ice-age atmospheric CO2 decline. 

PMID- 27029226
TI  - Genetic variation in SLC17A7 promoter associated with response to sport-related
      concussions.
AB  - OBJECTIVE: To determine the association of the single nucleotide polymorphism
      (SNP) rs74174284 within SLC17A7 promoter with concussion severity or duration.
      DESIGN: A between-subjects design was utilized. METHODS: Saliva samples and
      concussion severity and duration data were collected from 40 athletes diagnosed
      with a sport-related concussion by a physician, utilizing a standardized
      concussion assessment protocol. DNA was extracted, estimated and genotyped.
      RESULTS: An association was found between the dominant genetic model (CC vs GG +
      GC; p = 0.0179) and recovery, where those carrying the minor allele were 6.33
      times more likely to experience prolonged recovery rates. Within the ImPACT
      assessment, those carrying the CC genotype (33.38 +/- 10.15, p = 0.01) had worse
      motor speed scores upon initial assessment compared to both heterozygous (CG) and
      homozygous (GG) genotypes (41.59 +/- 7.39). CONCLUSIONS: This study was the first
      to demonstrate an association between genetic polymorphism at rs7417284 SNP in
      the promoter region of the SLC17A7 gene and concussion severity and duration.
      Based upon these findings, rs74174284 is a potential predictive genetic marker
      for identifying athletes who are more susceptible for altered recovery times and
      worse motor speed ImPACT scores after sport-related concussion.

PMID- 27029227
TI  - Robust band gap of TiS3 nanofilms.
AB  - First-principles calculations have been performed on the band structure of mono-
      and few-layer TiS3 nanofilms. It is found that the band gap character of the TiS3
      films is quite robust, almost independent of layer thickness, vertical strain and
      stacking order, which is in sharp contrast to most other two-dimensional
      materials, such as MoS2. The robustness of the band gap originates from the
      location of the CBM and VBM states, which are at the center atoms of TiS3, and
      are thus unaffected by the layer-layer coupling. Such a property of TiS3
      nanofilms promises good application potential in nanoelectronics and
      optoelectronics, and also makes TiS3 a good platform to study the electronic
      properties of a material in the two-dimensional limit.

PMID- 27029228
TI  - First-line response-adapted treatment with the combination of bendamustine and
      rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008
      01): a multicentre, single-arm, phase 2 trial.
AB  - BACKGROUND: No standard first-line systemic treatment for mucosa-associated
      lymphoid tissue (MALT) lymphoma is available. In a phase 2 study we aimed to
      assess the safety and activity of a response-adapted combination of bendamustine
      plus rituximab as upfront treatment for this type of lymphoma. METHODS: In a
      multicentre, single-arm, non-randomised, phase 2 trial, we enrolled patients with
      MALT lymphoma at any site and stage and treated them with bendamustine (90
      mg/m(2) on days 1 and 2) plus rituximab (375 mg/m(2) on day 1), every 4 weeks.
      Inclusion criteria were measurable or evaluable disease, age 18-85 years, and
      unequivocal active lymphoma; we also enrolled patients with MALT lymphoma arising
      in the stomach after failure of Helicobacter pylori eradication and primary
      cutaneous cases after failure of local therapies. Exclusion criteria included
      evidence of histological transformation, CNS involvement, and active hepatitis B
      or C virus or HIV infection. After three cycles, patients achieving complete
      response received one additional cycle (total four cycles) and those achieving
      partial response received three additional cycles (total six cycles). The primary
      endpoint was 2-year event-free survival. Analysis was by modified intention to
      treat. This trial is registered with ClinicalTrials.gov, number NCT01015248.
      FINDINGS: 60 patients from 19 centres in Spain were enrolled between May 27,
      2009, and May 23, 2011, and received treatment; 57 patients were evaluable for
      the primary endpoint. Only 14 (25%) patients needed more than four cycles of
      treatment. After a median follow-up of 43 months (IQR 37-51), median event-free
      survival was not reached. Event-free survival at 2 years was 93% (95% CI 84-97)
      and at 4 years was 88% (95% CI 74-95). The most frequently observed grade 3-4
      adverse events were haematological: lymphopenia in 20 (33%) patients, neutropenia
      in 12 (20%) patients, and leucopenia in three (5%) patients. Grade 3-4 febrile
      neutropenia or infections were reported in three (5%) and four (7%) patients,
      respectively. INTERPRETATION: This response-adapted schedule of bendamustine plus
      rituximab appears to be an active and well tolerated first-line treatment for
      patients with MALT lymphoma. FUNDING: Grupo Espanol de Linfomas/Trasplante de
      Medula Osea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.

PMID- 27029229
TI  - Thalidomide and prednisolone versus prednisolone alone as consolidation therapy
      after autologous stem-cell transplantation in patients with newly diagnosed
      multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label,
      randomised phase 3 study.
AB  - BACKGROUND: We previously showed that consolidation therapy with thalidomide and
      prednisolone improved progression-free and overall survival in patients with
      multiple myeloma who had undergone autologous stem-cell transplantation. We aimed
      to assess whether these survival advantages were durable at 5 years. METHODS: The
      ALLG MM6 trial was a multicentre, open-label, randomised phase 3 trial done
      between Jan 13, 2002, and March 15, 2005, at 29 sites in Australia and New
      Zealand. Patients with newly diagnosed multiple myeloma were randomly assigned
      (1:1), via computer-generated randomisation charts, to receive indefinite
      prednisolone maintenance alone (control group) or in combination with 12 months
      of thalidomide consolidation (thalidomide group) after autologous stem-cell
      transplantation. Randomisation was stratified by treating centre and pre
      transplantation concentrations of beta2 microglobulin. Patients and treating
      physicians were not masked to treatment allocation. Primary endpoints were
      progression-free survival and overall survival. Analysis was by intention to
      treat. Secondary endpoints were overall response to salvage therapy, incidence of
      second primary malignancy incidence, and cost-effectiveness. This trial is
      registered with the Australian and New Zealand Clinical Trials Registry, number
      ACTRN12607000382471. FINDINGS: We randomly assigned 269 patients to the
      thalidomide (n=114) or control group (n=129). After a median follow-up of 5.4
      years (IQR 3.1-7.2), estimated 5-year progression-free survival was 27% (95% CI
      23-32) in the thalidomide group and 15% (11-18) in the control group (hazard
      ratio [HR] 0.16, 95% CI 0.044-0.58; p=0.0054) and 5-year overall survival was 66%
      (95% CI 61-70) and 47% (42-51), respectively (HR 0.12, 95% CI 0.028-0.56;
      p=0.0072). There was no difference in overall response to salvage therapy,
      survival post-progression, or incidence of secondary malignancies between the two
      groups. Incremental cost-effectiveness ratio was AUS$26 996 per mean life-year
      gained. INTERPRETATION: Consolidation therapy with thalidomide and prednisolone
      after autologous stem-cell transplantaion is an acceptable therapeutic approach
      when alternative drugs are not available. FUNDING: Pharmion Corporation, Novartis
      Pharmaceuticals, Amgen Australia, The Merrin Foundation, and Alfred Health.

PMID- 27029230
TI  - Blood transfusion: optimising resources.

PMID- 27029231
TI  - Nitric oxide-based treatment for sickle cell leg ulcers?

PMID- 27029232
TI  - Bendamustine plus rituximab in MALT lymphoma.

PMID- 27029233
TI  - Post-transplant therapy in multiple myeloma: a hung jury?

PMID- 27029234
TI  - Rethinking ferritin cutoffs for iron deficiency and overload.

PMID- 27029235
TI  - Measures for screening for intimate partner violence: a systematic review.
AB  - WHAT IS KNOWN ON THE SUBJECT?: Intimate partner violence (IPV) has a significant
      impact on the onset, duration and recurrence of mental health problems.
      Prevalence rates of IPV are significantly higher in mental health services, but
      the studies are limited. Accurate assessment of IPV is important for decision
      making in risk assessment and safety planning within mental health nursing.
      Psychometrically tested tools are the most accurate way to identifying all areas
      of IPV abuse: physical, sexual and psychological. WHAT THIS PAPER ADDS TO
      EXISTING KNOWLEDGE?: Ten IPV screening tools were identified in healthcare and
      three tools; Women Abuse Screen Tool (WAST), Abuse Assessment Screen (AAS) and
      Humiliation, Afraid, Rape and Kick (HARK) were identified as having strong
      psychometric values as they assessed all areas of IPV and were validated against
      an appropriate reference standard. None of the three IPV tools identified (WAST,
      AAS, HARK) were tested on men or in mental health settings impacting the gender
      sensitivities of the tools and the reliability of the prevalence rates of IPV in
      mental healthcare. Over seventy percent of the studies reviewed were conducted in
      America this impacts the cultural sensitivities of the IPV tools. WHAT ARE THE
      IMPLICATIONS FOR PRACTICE?: IPV screening needs to be incorporated as a priority
      in mental health services in order to reduce the morbidity and mortality issues
      associated with this abuse. Psychometric tools to screen for IPV need to be
      incorporated to assist mental health professionals in decision making in risk
      assessment and safety planning. Further research is needed to improve the
      psychometric properties of IPV tools in mental health settings, to ensure they
      are culturally and gender sensitive. ABSTRACT: Objective Intimate partner
      violence (IPV) is a public health priority due to the physical and mental impacts
      it has on health. No existing reviews have focused on the psychometric properties
      of IPV screening tools used to screen men and women within a mental health
      context. This review aimed to identify the best psychometrically tested screening
      tools available to assess all areas of IPV in men and women in mental health
      setting. Method Databases psycArticles, PsycINFO, Social Science, CINAHL, PubMed
      and Cochrane were searched from their starting date through to July 2015.
      Eligible studies were published in peer-reviewed publications in English. Results
      Thirty-six studies met the inclusion criteria. Ten IPV screening tools were
      identified. Three tools assessed all areas of IPV and were validated against an
      appropriate reference standard. One study tested IPV screening tool in a mental
      health setting. Conclusion Mental health nurses need to incorporate a
      psychometrically tested IPV tool as part of risk assessment and safety planning
      for clients. This review identified three tools that are suitable for identifying
      IPV in a mental health context. However, further research is necessary to
      validate IPV screening tools that are culturally sensitive and have been
      validated with men and women.

PMID- 27029236
TI  - Partial response after induction chemotherapy has clinical relevance in acute
      myeloid leukaemia.

PMID- 27029237
TI  - Comparing guideline-based care quality for inflammatory bowel disease and
      rheumatoid arthritis patients within a medical home.
AB  - BACKGROUND: Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD)
      patient populations face similar risks of chronic immunosuppression including
      corticosteroid use. We compared the receipt of preventive services between IBD
      and RA populations according to published quality metrics. METHODS: We defined a
      single-center cohort of patients with IBD or RA receiving specialty and primary
      care. Electronic health record abstraction assessed quality metrics,
      sociodemographics, comorbidity, and utilization. Comparisons used multivariate
      odds ratios and Student's t-tests. RESULTS: 218 RA and 190 IBD patients were
      included. In multivariate analysis, IBD patients were less likely to receive
      pneumococcal vaccination (OR=0.29, 95% CI: 0.11-0.85), while RA patients
      underwent glucocorticoid-induced osteoporosis screening more often (100% vs.
      82.5%, p = 0.023). CONCLUSIONS: Gastroenterologists can improve care quality for
      IBD patients by assuming greater responsibility for preventive care in IBD
      patients and/or collaborating with primary care and health systems to improve
      preventive care delivery.

PMID- 27029239
TI  - School and Community Screening Shows Malawi, Africa, to Have a High Prevalence of
      Latent Rheumatic Heart Disease.
AB  - : Rheumatic heart disease (RHD) is the largest cardiac cause of morbidity and
      mortality in the world's youth. Early detection of RHD through echocardiographic
      screening in asymptomatic children may identify an early stage of disease, when
      secondary prophylaxis has the greatest chance of stopping disease progression.
      Latent RHD signifies echocardiographic evidence of RHD with no known history of
      acute rheumatic fever and no clinical symptoms. OBJECTIVE: Determine the
      prevalence of latent RHD among children ages 5-16 in Lilongwe, Malawi. DESIGN:
      This is a cross-sectional study in which children ages 5 through 16 were screened
      for RHD using echocardiography. SETTING: Screening was conducted in 3 schools and
      surrounding communities in the Lilongwe district of Malawi between February and
      April 2014. OUTCOME MEASURES: Children were diagnosed as having no, borderline,
      or definite RHD as defined by World Heart Federation criteria. The primary reader
      completed offline reads of all studies. A second reader reviewed all of the
      studies diagnosed as RHD, plus a selection of normal studies. A third reader
      served as tiebreaker for discordant diagnoses. The distribution of results was
      compared between gender, location, and age categories using Fisher's exact test.
      RESULTS: The prevalence of latent RHD was 3.4% (95% CI = 2.45, 4.31), with 0.7%
      definite RHD and 2.7% borderline RHD. There was no significant differences in
      prevalence between gender (P = .44), site (P = .6), urban vs. peri-urban (P =
      .75), or age (P = .79). Of those with definite RHD, all were diagnosed because of
      pathologic mitral regurgitation (MR) and 2 morphologic features of the mitral
      valve. Of those with borderline RHD, most met the criteria by having pathological
      MR (92.3%). CONCLUSION: Malawi has a high rate of latent RHD, which is consistent
      with other results from sub-Saharan Africa. This study strongly supports the need
      for a RHD prevention and control program in Malawi.

PMID- 27029238
TI  - Effective heterogeneous transition metal glycerolates catalysts for one-step
      biodiesel production from low grade non-refined Jatropha oil and crude aqueous
      bioethanol.
AB  - The utilization of bioethanol as the alcohol source for biodiesel production is
      more environmentally advantageous over methanol owing to its lower toxicity,
      lower flammability and its sustainable supply from renewable agricultural
      resources. However, as the presence of water in crude bioethanol is the critical
      factor limiting the biodiesel production process, the energy-intensive and costly
      purification of bioethanol is necessary for biodiesel application. Manganese
      glycerolate (MnGly) is reported the first time here as a robust heterogeneous
      catalyst that exhibited over 90% conversion by using aqueous ethanol containing
      80 wt.% of water in the production of fatty acid ethyl ester (FAEE). The
      employment of 95 wt.% ethanol with respect to water could achieve 99.7% feedstock
      conversion in 6 hours under the optimal reaction conditions: reaction temperature
      (150  degrees C), feedstock-to-ethanol molar ratio (1:20) and catalyst loading (6
      wt.%). Commercially available low grade crude bioethanol with the presence of
      impurities like sugars were applied which demonstrated remarkable catalytic
      activity in 24 hours. The high water tolerance of MnGly towards biodiesel
      production could eventually simplify the purification of bioethanol that consumes
      less energy and production cost. 

PMID- 27029240
TI  - Effect of amlodipine on mouse renal interstitial fibrosis.
AB  - Unilateral ureteral obstruction (UUO) is a well-established method to study
      interstitial fibrosis of the kidney. In this study, we investigated the effects
      of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial
      fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed
      kidney, but this change was inhibited by amlodipine (6.7mg/kg/day in drinking
      water). mRNA expression of heat shock protein (HSP) 47 and type IV collagen was
      increased in the kidneys of UUO mice. Amlodipine reduced the expression of both
      HSP47 and type IV collagen mRNAs. Phosphorylation of c-jun-N-terminal kinase
      (JNK) was significantly increased by UUO, but the change was inhibited by
      amlodipine. Collectively, these results suggest that amlodipine may inhibit the
      expression of HSP47 and type IV collagen by reducing phosphorylation of JNK and
      ameliorating the renal interstitial fibrosis induced by UUO. 

PMID- 27029241
TI  - Time out.

PMID- 27029242
TI  - Play nicely.

PMID- 27029243
TI  - Honey trap.

PMID- 27029244
TI  - Sugar tax could sweeten a market failure.

PMID- 27029256
TI  - 'Minimal' cell raises stakes in race to harness synthetic life.

PMID- 27029257
TI  - Scientists say 'no' to UK exit from Europe in Nature poll.

PMID- 27029258
TI  - Biological specimen troves threatened by funding pause.

PMID- 27029260
TI  - 24 hours at the X-ray factory.

PMID- 27029259
TI  - Antarctic model raises prospect of unstoppable ice collapse.

PMID- 27029261
TI  - Can a video game company tame toxic behaviour?

PMID- 27029262
TI  - Technology: Use or lose our navigation skills.

PMID- 27029267
TI  - Germany: One of animal-study criteria backfires.

PMID- 27029268
TI  - Sterilization techniques: Counter the risk of Alzheimer's transfer.

PMID- 27029269
TI  - Government cuts: Fanning the flames of Australian wildfires.

PMID- 27029270
TI  - Researcher incentives: EU cash goes to the sticky and attractive.

PMID- 27029271
TI  - Pollution: Too many mining disasters in Brazil.

PMID- 27029272
TI  - Applied physics: Gravity measurements on chips.

PMID- 27029273
TI  - Physical chemistry: A close-up view of coupled molecules.

PMID- 27029274
TI  - Contribution of Antarctica to past and future sea-level rise.
AB  - Polar temperatures over the last several million years have, at times, been
      slightly warmer than today, yet global mean sea level has been 6-9 metres higher
      as recently as the Last Interglacial (130,000 to 115,000 years ago) and possibly
      higher during the Pliocene epoch (about three million years ago). In both cases
      the Antarctic ice sheet has been implicated as the primary contributor, hinting
      at its future vulnerability. Here we use a model coupling ice sheet and climate
      dynamics-including previously underappreciated processes linking atmospheric
      warming with hydrofracturing of buttressing ice shelves and structural collapse
      of marine-terminating ice cliffs-that is calibrated against Pliocene and Last
      Interglacial sea-level estimates and applied to future greenhouse gas emission
      scenarios. Antarctica has the potential to contribute more than a metre of sea
      level rise by 2100 and more than 15 metres by 2500, if emissions continue
      unabated. In this case atmospheric warming will soon become the dominant driver
      of ice loss, but prolonged ocean warming will delay its recovery for thousands of
      years. 

PMID- 27029276
TI  - Measurement of the Earth tides with a MEMS gravimeter.
AB  - The ability to measure tiny variations in the local gravitational acceleration
      allows, besides other applications, the detection of hidden hydrocarbon reserves,
      magma build-up before volcanic eruptions, and subterranean tunnels. Several
      technologies are available that achieve the sensitivities required for such
      applications (tens of microgal per hertz(1/2)): free-fall gravimeters, spring
      based gravimeters, superconducting gravimeters, and atom interferometers. All of
      these devices can observe the Earth tides: the elastic deformation of the Earth's
      crust as a result of tidal forces. This is a universally predictable
      gravitational signal that requires both high sensitivity and high stability over
      timescales of several days to measure. All present gravimeters, however, have
      limitations of high cost (more than 100,000 US dollars) and high mass (more than
      8 kilograms). Here we present a microelectromechanical system (MEMS) device with
      a sensitivity of 40 microgal per hertz(1/2) only a few cubic centimetres in size.
      We use it to measure the Earth tides, revealing the long-term stability of our
      instrument compared to any other MEMS device. MEMS accelerometers--found in most
      smart phones--can be mass-produced remarkably cheaply, but none are stable enough
      to be called a gravimeter. Our device has thus made the transition from
      accelerometer to gravimeter. The small size and low cost of this MEMS gravimeter
      suggests many applications in gravity mapping. For example, it could be mounted
      on a drone instead of low-flying aircraft for distributed land surveying and
      exploration, deployed to monitor volcanoes, or built into multi-pixel density
      contrast imaging arrays.

PMID- 27029275
TI  - Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome.
AB  - The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in
      humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their
      ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2))
      monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is
      inactive in the absence of damaged DNA and requires CSN to regulate the repair
      process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of
      CSN activation are poorly understood. Here we present cryo-electron microscopy
      structures for CSN in complex with neddylated CRL4A ligases to 6.4 A resolution.
      The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN
      crystal structure indicate an induced-fit mechanism that drives CSN activation by
      neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to
      CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4
      complexes. These architectural and regulatory principles appear conserved across
      CRL families, allowing global regulation by CSN. 

PMID- 27029277
TI  - Visualizing coherent intermolecular dipole-dipole coupling in real space.
AB  - Many important energy-transfer and optical processes, in both biological and
      artificial systems, depend crucially on excitonic coupling that spans several
      chromophores. Such coupling can in principle be described in a straightforward
      manner by considering the coherent intermolecular dipole-dipole interactions
      involved. However, in practice, it is challenging to directly observe in real
      space the coherent dipole coupling and the related exciton delocalizations, owing
      to the diffraction limit in conventional optics. Here we demonstrate that the
      highly localized excitations that are produced by electrons tunnelling from the
      tip of a scanning tunnelling microscope, in conjunction with imaging of the
      resultant luminescence, can be used to map the spatial distribution of the
      excitonic coupling in well-defined arrangements of a few zinc-phthalocyanine
      molecules. The luminescence patterns obtained for excitons in a dimer, which are
      recorded for different energy states and found to resemble sigma and pi molecular
      orbitals, reveal the local optical response of the system and the dependence of
      the local optical response on the relative orientation and phase of the
      transition dipoles of the individual molecules in the dimer. We generate an in
      line arrangement up to four zinc-phthalocyanine molecules, with a larger total
      transition dipole, and show that this results in enhanced 'single-molecule'
      superradiance from the oligomer upon site-selective excitation. These findings
      demonstrate that our experimental approach provides detailed spatial information
      about coherent dipole-dipole coupling in molecular systems, which should enable a
      greater understanding and rational engineering of light-harvesting structures and
      quantum light sources. 

PMID- 27029278
TI  - Komatiites reveal a hydrous Archaean deep-mantle reservoir.
AB  - Archaean komatiites (ultramafic lavas) result from melting under extreme
      conditions of the Earth's mantle. Their chemical compositions evoke very high
      eruption temperatures, up to 1,600 degrees Celsius, which suggests even higher
      temperatures in their mantle source. This message is clouded, however, by
      uncertainty about the water content in komatiite magmas. One school of thought
      holds that komatiites were essentially dry and originated in mantle plumes while
      another argues that these magmas contained several per cent water, which
      drastically reduced their eruption temperature and links them to subduction
      processes. Here we report measurements of the content of water and other volatile
      components, and of major and trace elements in melt inclusions in exceptionally
      magnesian olivine (up to 94.5 mole per cent forsterite). This information
      provides direct estimates of the composition and crystallization temperature of
      the parental melts of Archaean komatiites. We show that the parental melt for 2.7
      billion-year-old komatiites from the Abitibi greenstone belt in Canada contained
      30 per cent magnesium oxide and 0.6 per cent water by weight, and was depleted in
      highly incompatible elements. This melt began to crystallize at around 1,530
      degrees Celsius at shallow depth and under reducing conditions, and it evolved
      via fractional crystallization of olivine, accompanied by minor crustal
      assimilation. As its major- and trace-element composition and low oxygen
      fugacities are inconsistent with a subduction setting, we propose that its high
      H2O/Ce ratio (over 6,000) resulted from entrainment into the komatiite source of
      hydrous material from the mantle transition zone. These results confirm a plume
      origin for komatiites and high Archaean mantle temperatures, and evoke a hydrous
      reservoir in the deep mantle early in Earth's history. 

PMID- 27029280
TI  - Largest ever study of transgender teenagers set to kick off.

PMID- 27029281
TI  - Where have all the inosines gone? Conflicting evidence for A-to-I editing of the
      anticodon of higher eukaryotic tRNAACGArg questions the dogma of a universal
      wobble-mediated decoding of CGN codons.
AB  - Codon-anticodon recognition between triplets of an mRNA and a specific tRNA is
      the key element in the translation of the genetic code. In general, the precision
      of this process is dominated by a strict Watson-Crick base-pairing scheme.
      However, the degeneracy of the genetic code led Crick to propose the Wobble
      Hypothesis, permitting a less restraining interaction with the third base of the
      codon and involving the participation of inosine for decoding C-ending codons.
      The concept that the anticodon base A34 of tRNAACGArg in all eukaryotes,
      eubacteria, and plant chloroplasts is converted to I34 is firmly anchored in the
      literature despite conflicting evidence for its existence in higher eukaryote
      cytoplasmic tRNAACGArg. Here, we provide additional data and summarize the
      arguments favoring and contradicting post-transcriptional deamination of this
      position. A hypothesis that resolves the apparent conflict is proposed. (c) 2016
      IUBMB Life, 68(6):419-422, 2016.

PMID- 27029282
TI  - Positron detection in silica monoliths for miniaturised quality control of PET
      radiotracers.
AB  - We demonstrate the use of the miniaturised Medipix positron sensor for detection
      of the clinical PET radiotracer, [(68)Ga]gallium-citrate, on a silica-based
      monolith, towards microfluidic quality control. The system achieved a far
      superior signal-to-noise ratio compared to conventional sodium iodide-based radio
      HPLC detection and allowed real-time visualisation of positrons in the monolith. 

PMID- 27029283
TI  - Does Bedside Sonography Effectively Identify Nasogastric Tube Placements in
      Pediatric Critical Care Patients?
AB  - BACKGROUND: A nasogastric tube (NGT) insertion is a common procedure in intensive
      care units, with some serious complications that result from the malposition of
      the NGT tip. This pilot study was designed to investigate the efficiency of
      ultrasound in verifying correct NGT placement and to compare these results with
      radiographic findings. MATERIALS AND METHODS: This was a single-center, double
      blind prospective study of patients who had received an NGT in the pediatric
      critical care unit. Twenty-one patients aged 1 month to 18 years were included in
      this study. All NGTs were inserted by the same critical care physician. After
      insertion, the physician first confirmed NGT placement by the auscultation of the
      epigastrium following the insufflation of air. Confirmation was supplemented with
      an abdominal radiograph. A radiologist who was unaware of the radiographic
      findings performed bedside sonography on all patients and verified the location
      of the NGTs. The findings from these 2 physicians were then compared. RESULTS:
      NGTs were inserted without any complications, and none of the NGTs were
      positioned in the respiratory tract in any of the patients. All NGT tips were
      visualized by radiography and sonography with a sensitivity of 100%. CONCLUSION:
      Bedside sonography performed by a radiologist is an effective and sensitive
      diagnostic procedure for confirming the correct NGT position in patients in the
      pediatric critical care unit.

PMID- 27029284
TI  - Comparison of dual antiplatelet therapy prescribed as one-pill versus two-pill
      regimen. A pooled analysis of individual patient data from the three MR-CAPCIS
      trials.
AB  - Fixed-dose combination (FDC) drugs can simplify the medication regimen and
      potentially improve adherence. However, evidence is lacking about the efficacy
      and safety of FDC drugs of clopidogrel plus aspirin. Individual data from the
      three independent MR-CAPCIS trials were pooled and analysed. In those trials,
      subjects who had been treated with either dual antiplatelet therapy (DAPT) or
      aspirin alone after drug-eluting stent (DES) implantation were randomly assigned
      to one-pill or to two-pill DAPT group. Platelet reactivity was measured with
      VerifyNow-P2Y12 and aspirin point-of-care assays at baseline and eight weeks
      after treatment. In the present study, primary efficacy endpoint was changes in
      platelet reactivity unit (PRU) between baseline and eight weeks. A total of 965
      subjects were analysed. In prior clopidogrel and aspirin users, PRU was well
      maintained regardless of switching to either one-pill or two-pill DAPT
      (DeltaPRU=0.4 vs 0.0, p=0.939). In prior aspirin users, PRU was decreased by 73.7
      in one-pill DAPT and 77.5 in two-pill DAPT group, with no differences between
      them (p=0.499). The incidence of high on-treatment platelet reactivity at eight
      weeks, defined as PRU>=235 in Western people, was 34.8 % in one-pill DAPT group
      and 37.6 % in two-pill DAPT group (p=0.380), and that defined as PRU >=275 in
      Oriental people was 17.7 vs 21.7 % (p=0.129). Independent predictors of high
      platelet reactivity on clopidogrel were female gender, increasing age, and
      diabetes. Study drugs were well tolerated. In conclusion, FDC one-pill DAPT
      showed similar efficacy to two-pill DAPT in terms of platelet reactivity in
      patients receiving DES in Korea.

PMID- 27029286
TI  - PRD-1, a Component of the Circadian System of Neurospora crassa, Is a Member of
      the DEAD-box RNA Helicase Family.
AB  - The circadian rhythms found in almost all organisms are driven by molecular
      oscillators, including transcription/translation feedback loops (TTFLs). However,
      TTFL-independent oscillators can drive rhythms in both eukaryotes and
      prokaryotes. The fungus Neurospora crassa is a model organism for studying the
      molecular mechanism of the circadian clock. Although a circadian TTFL involving
      the proteins FRQ, WC-1, and WC-2 is well-characterized in N. crassa, rhythms can
      still be observed in the absence of this feedback loop. These rhythms are said to
      be driven by 1 or more FRQ-less oscillator(s) (FLOs). The prd-1 mutation
      lengthens the period in frq wild type and was previously shown to severely
      disrupt FRQ-less rhythms in frq null mutants under several different conditions;
      therefore, the prd-1 gene product is a candidate for a component of a FLO. We
      report here that prd-1 also disrupts free-running rhythms in wc-1 null mutants,
      confirming its effects on FRQ-less rhythms. We have now mapped and identified the
      prd-1 gene as NCU07839, a DEAD-box RNA helicase dbp-2 Complementation with the
      wild-type gene corrects the rhythm defects of the prd-1 mutant in the complete
      circadian system (when the FRQ-based TTFL is intact) and also the free-running
      FRQ-less rhythm on low choline. A PRD-1-GFP fusion protein localizes to the
      nucleus. The prd-1 mutant has a single base pair change in the first base of an
      intron that results in abnormally spliced transcripts. FRQ-less rhythms on low
      choline, or entrained to heat pulses, were only marginally affected in strains
      carrying deletions of 2 other RNA helicases (prd-6 and msp-8). We conclude that
      PRD-1 is a member of an RNA helicase family that may be specifically involved in
      regulating rhythmicity in N. crassa in both the complete circadian system and
      FLO(s).

PMID- 27029285
TI  - Direct observation of intermediate states in model membrane fusion.
AB  - We introduce a novel assay for membrane fusion of solid supported membranes on
      silica beads and on coverslips. Fusion of the lipid bilayers is induced by
      bringing an optically trapped bead in contact with the coverslip surface while
      observing the bead's thermal motion with microsecond temporal and nanometer
      spatial resolution using a three-dimensional position detector. The probability
      of fusion is controlled by the membrane tension on the particle. We show that the
      progression of fusion can be monitored by changes in the three-dimensional
      position histograms of the bead and in its rate of diffusion. We were able to
      observe all fusion intermediates including transient fusion, formation of a
      stalk, hemifusion and the completion of a fusion pore. Fusion intermediates are
      characterized by axial but not lateral confinement of the motion of the bead and
      independently by the change of its rate of diffusion due to the additional drag
      from the stalk-like connection between the two membranes. The detailed
      information provided by this assay makes it ideally suited for studies of early
      events in pure lipid bilayer fusion or fusion assisted by fusogenic molecules. 

PMID- 27029287
TI  - Can concern for the long-term care of older parents explain son preference at
      birth in India?
AB  - This study examines whether concern for the long-term care of older parents is
      the primary reason for son preference in India. Controlling for important
      socioeconomic factors that are believed to affect son preference, we find that
      concern for long-term care is the principal cause of son preference in India.
      Sons serve as the primary caregivers to elderly parents, while daughters are
      mostly engaged in caring for parents-in-law. This trend is more acute in rural
      than in urban areas. Our study also finds a strong implication of the filial
      relationship for the long-term care of elderly parents.

PMID- 27029288
TI  - Efficacy and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower
      Respiratory Tract Infections.
AB  - BACKGROUND: In 14 randomized controlled studies to date, a procalcitonin (PCT)
      based algorithm has been proven to markedly reduce the use of antibiotics along
      with an unimpaired high safety and low complication rates in patients with lower
      respiratory tract infections (LRTIs). However, compliance with the algorithm and
      safety out of controlled study conditions has not yet been sufficiently
      investigated. METHODS: We performed a prospective international multicenter
      observational post-study surveillance of consecutive adults with community
      acquired LRTI in 14 centers (Switzerland (n = 10), France (n = 3) and the United
      States (n = 1)). RESULTS: Between September 2009 and November 2010, 1,759
      patients were enrolled (median age 71; female sex 44.4%). 1,520 (86.4%) patients
      had a final diagnosis of LRTI (community-acquired pneumonia (CAP), 53.7%; acute
      exacerbation of chronic obstructive pulmonary disease (AECOPD), 17.1%; and acute
      bronchitis, 14.4%). Compliance with the PCT-guided therapy (overall 68.2%) was
      highest in patients with bronchitis (81.0% vs. AECOPD, 70.1%; CAP, 63.7%; p <
      0.001), outpatients (86.1% vs. inpatients, 65.9%; p < 0.001) and algorithm
      experienced centers (82.5% vs. algorithm-naive, 60.1%; p < 0.001) and showed
      significant geographical differences. The initial decision about the antibiotic
      therapy was based on PCT value in 72.4%. In another 8.6% of patients, antibiotics
      were administered despite low PCT values but according to predefined criteria.
      Thus, the algorithm was followed in 81.0% of patients. In a multivariable Cox
      hazard ratio model, longer antibiotic therapy duration was associated with
      algorithm-non-compliance, country, hospitalization, CAP vs. bronchitis, renal
      failure and algorithm-naivety of the study center. In a multivariable logistic
      regression complications (death, empyema, ICU treatment, mechanical ventilation,
      relapse, and antibiotic-associated side effects) were significantly associated
      with increasing CURB65-Score, CAP vs. bronchitis, multilobar pneumonia, but not
      with algorithm-compliance. DISCUSSION: Cultural and geographic differences in
      antibiotic prescribing affected the compliance with our PCT-guided algorithm.
      Efforts to reinforce compliance are needed. Antibiotic stewardship with PCT is
      possible, effective and safe without increasing the risk of complications in real
      life conditions.

PMID- 27029289
TI  - The Staphylococcus aureus Membrane Protein SA2056 Interacts with Peptidoglycan
      Synthesis Enzymes.
AB  - The yet uncharacterized membrane protein SA2056 belongs to the ubiquitous RND
      (Resistance-Nodulation-cell Division) family of transmembrane efflux
      transporters. The sa2056 gene is located downstream of femX, the gene encoding
      the essential, non-ribosomal peptidyl-transferase adding the first glycine in the
      staphylococcal cell wall pentaglycine interpeptide. Due to its proximity to and
      weak co-transcription with femX, we assumed that sa2056 may somehow be involved
      in peptidoglycan synthesis. Specific antibodies against SA2056 showed that this
      protein is expressed during growth and present in the membrane fraction of cell
      preparations. Using a bacterial two hybrid system, SA2056 was shown to interact
      (i) with itself, (ii) with FemB, which adds glycines 4 and 5 to the peptidoglycan
      interpeptide and (iii) with the essential penicillin binding proteins, PBP1 and
      PBP2, required for cell division and incorporation of the peptidoglycan into the
      cell wall. Unexpectedly, deletion of sa2056 led to no phenotype regarding growth,
      antibiotic resistances or cell morphology; nor did sa2056 deletion in combination
      with femB inactivation alter b-lactam and lysostaphin sensitivity and resistance,
      respectively, pointing to possible redundancy in the cell wall synthesis pathway.
      These results suggest an accessory role of SA2056 in S. aureus peptidoglycan
      synthesis, broadening the range of biological functions of RND proteins. 

PMID- 27029290
TI  - Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram
      Positive Bacteria S. aureus.
AB  - The paper focuses on recent achievements in the search for new chemical compounds
      able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens.
      An analysis of the results of the search for new efflux pump inhibitors (EPIs)
      for Gram-positive bacteria, which have been performed over the last decade,
      indicates that almost all efforts are focused on the NorA (MFS) efflux pump in S.
      aureus. Considering the chemical structures of the NorA EPIs that have been
      identified, it can be observed that the most active agents belong to the families
      of compounds possessing conjugated double bonds, e.g., chalcones, piperine-like
      compounds, N-cinnamoylphenalkylamides or citral amide derivatives. Indole-,
      dihydronaphthyl-, 2-chloro-5-bromo-phenyl- or piperidine moieties seem to be
      profitable for the EPI properties, as well. These results, together with an
      increasing knowledge about a variety of efflux pumps that are involved in MDR of
      Gram-positive pathogens underline that further search for new EPIs should pay
      more attention to develop MDR efflux protein targets, including SMR, MATE, ABC or
      other members of the MFS family. 

PMID- 27029291
TI  - Determination of the Presence of Three Antimicrobials in Surface Water Collected
      from Urban and Rural Areas.
AB  - Due to the continuous release of antimicrobials into the environment, the aim of
      this study was to compare the frequency of detection of sulfamethazine,
      sulfamethoxypyridazine and trimethoprim in surface water collected from urban and
      rural areas in Northwestern Spain. A monitoring study was conducted with 314
      river water samples analyzed by high-performance liquid chromatography coupled to
      tandem mass spectrometry. The results indicated that 37% of the samples contained
      residues of at least one of the investigated antimicrobials, and every sampling
      site yielded positive samples. At sites located near the discharge points of
      wastewater treatment plants and near the collection point of a drinking-water
      treatment plant, more than 6% of the samples were positive for the presence of
      antimicrobial residues. 

PMID- 27029293
TI  - Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth
      against Meropenem in a Murine Thigh Infection Model.
AB  - Acinetobacter baumannii may exhibit phenotypic heterogeneous growth under
      exposure to antibiotics. We investigated the in vitro characteristics of A.
      baumannii isolates grown heterogeneously in the presence of meropenem and their
      virulence evaluated in experimental infections treated with meropenem. Five
      clinical A. baumannii isolates and the respective heterogeneously grown
      subpopulations were tested by agar dilution minimum inhibitory concentration
      (MIC) testing, pulsed field gel electrophoresis (PFGE), population analysis using
      meropenem and growth curves. The virulence of isolates and the therapeutic
      efficacy of three meropenem dosing schemes was evaluated in a neutropenic murine
      thigh infection model. The clinical isolates were meropenem-susceptible (MICs 1
      to 4 mg/liter) and exhibited three distinct PFGE patterns. In all clinical
      isolates, population analysis yielded heterogeneously grown colonies. After seven
      subcultures in antibiotic-free media, resistant MIC levels were retained in two
      isolates (heteroresistant), while three isolates were reversed to susceptible
      MICs (persisters). Clinical isolates and heterogeneous subpopulations had similar
      growth rates. The heterogeneously grown A. baumannii subpopulations had reduced
      virulence, killing considerably fewer animals than the respective clinical
      isolates without treatment. The meropenem treatment outcome was similar in
      infections caused by the clinical and the heterogeneous isolates, irrespective to
      their MICs. In vitro meropenem exposure induces phenotypic heterogeneous growth
      in A. baumannii. Compared with the parental clinical isolates, the
      heterogeneously grown subpopulations exhibited lower virulence, killing fewer
      mice and responding equally to meropenem treatment, despite their higher MICs. 

PMID- 27029292
TI  - Role of Phenothiazines and Structurally Similar Compounds of Plant Origin in the
      Fight against Infections by Drug Resistant Bacteria.
AB  - Phenothiazines have their primary effects on the plasma membranes of prokaryotes
      and eukaryotes. Among the components of the prokaryotic plasma membrane affected
      are efflux pumps, their energy sources and energy providing enzymes, such as
      ATPase, and genes that regulate and code for the permeability aspect of a
      bacterium. The response of multidrug and extensively drug resistant tuberculosis
      to phenothiazines shows an alternative therapy for the treatment of these dreaded
      diseases, which are claiming more and more lives every year throughout the world.
      Many phenothiazines have shown synergistic activity with several antibiotics
      thereby lowering the doses of antibiotics administered to patients suffering from
      specific bacterial infections. Trimeprazine is synergistic with trimethoprim.
      Flupenthixol (Fp) has been found to be synergistic with penicillin and
      chlorpromazine (CPZ); in addition, some antibiotics are also synergistic. Along
      with the antibacterial action described in this review, many phenothiazines
      possess plasmid curing activities, which render the bacterial carrier of the
      plasmid sensitive to antibiotics. Thus, simultaneous applications of a
      phenothiazine like TZ would not only act as an additional antibacterial agent but
      also would help to eliminate drug resistant plasmid from the infectious bacterial
      cells. 

PMID- 27029294
TI  - Resistance to Antimicrobials Mediated by Efflux Pumps in Staphylococcus aureus.
AB  - Resistance mediated by efflux has been recognized in Staphylococcus aureus in the
      last few decades, although its clinical relevance has only been recognized
      recently. The existence of only a few studies on the individual and overall
      contribution of efflux to resistance phenotypes associated with the need of well
      established methods to assess efflux activity in clinical isolates contributes
      greatly to the lack of solid knowledge of this mechanism in S. aureus. This study
      aims to provide information on approaches useful to the assessment and
      characterization of efflux activity, as well as contributing to our understanding
      of the role of efflux to phenotypes of antibiotic resistance and biocide
      tolerance in S. aureus clinical isolates. The results described show that efflux
      is an important contributor to fluoroquinolone resistance in S. aureus and
      suggest it as a major mechanism in the early stages of resistance development. We
      also show that efflux plays an important role on the reduced susceptibility to
      biocides in S. aureus, strengthening the importance of this long neglected
      resistance mechanism to the persistence and proliferation of antibiotic/biocide
      resistant S. aureus in the hospital environment. 

PMID- 27029295
TI  - Bacterial Responses and Genome Instability Induced by Subinhibitory
      Concentrations of Antibiotics.
AB  - Nowadays, the emergence and spread of antibiotic resistance have become an utmost
      medical and economical problem. It has also become evident that subinhibitory
      concentrations of antibiotics, which pollute all kind of terrestrial and aquatic
      environments, have a non-negligible effect on the evolution of antibiotic
      resistance in bacterial populations. Subinhibitory concentrations of antibiotics
      have a strong effect on mutation rates, horizontal gene transfer and biofilm
      formation, which may all contribute to the emergence and spread of antibiotic
      resistance. Therefore, the molecular mechanisms and the evolutionary pressures
      shaping the bacterial responses to subinhibitory concentrations of antibiotics
      merit to be extensively studied. Such knowledge is valuable for the development
      of strategies to increase the efficacy of antibiotic treatments and to extend the
      lifetime of antibiotics used in therapy by slowing down the emergence of
      antibiotic resistance. 

PMID- 27029296
TI  - An Environmental Risk Assessment for Human-Use Trimethoprim in European Surface
      Waters.
AB  - An environmental risk assessment (ERA) for the aquatic compartment in Europe from
      human use was developed for the old antibiotic Trimethoprim (TMP), comparing
      exposure and effects. The exposure assessment is based on European risk
      assessment default values on one hand and is refined with documented human use
      figures in Western Europe from IMS Health and measured removal in wastewater
      treatment on the other. The resulting predicted environmental concentrations
      (PECs) are compared with measured environmental concentrations (MECs) from
      Europe, based on a large dataset incorporating more than 1800 single MECs. On the
      effects side, available chronic ecotoxicity data from the literature were
      complemented by additional, new chronic results for fish and other organisms.
      Based on these data, chronic-based deterministic predicted no effect
      concentrations (PNECs) were derived as well as two different probabilistic PNEC
      ranges. The ERA compares surface water PECs and MECs with aquatic PNECs for TMP.
      Based on all the risk characterization ratios (PEC/PNEC as well as MEC/PNEC) and
      risk graphs, there is no significant risk to surface waters. 

PMID- 27029297
TI  - Resistance-Nodulation-Division Multidrug Efflux Pumps in Gram-Negative Bacteria:
      Role in Virulence.
AB  - Resistance-Nodulation-Division (RND) efflux pumps are one of the most important
      determinants of multidrug resistance (MDR) in Gram-negative bacteria. With an
      ever increasing number of Gram-negative clinical isolates exhibiting MDR
      phenotypes as a result of the activity of RND pumps, it is clear that the design
      of novel effective clinical strategies against such pathogens must be grounded in
      a better understanding of these pumps, including their physiological roles. To
      this end, recent evidence suggests that RND pumps play an important role in the
      virulence of Gram-negative pathogens. In this review, we discuss the important
      role RND efflux pumps play in different facets of virulence including
      colonization, evasion of host defense mechanisms, and biofilm formation. These
      studies provide key insights that may ultimately be applied towards strategies
      used in the design of effective therapeutics against MDR Gram negative bacterial
      pathogens. 

PMID- 27029298
TI  - Tracking Change: A Look at the Ecological Footprint of Antibiotics and
      Antimicrobial Resistance.
AB  - Among the class of pollutants considered as 'emerging contaminants', antibiotic
      compounds including drugs used in medical therapy, biocides and disinfectants
      merit special consideration because their bioactivity in the environment is the
      result of their functional design. Antibiotics can alter the structure and
      function of microbial communities in the receiving environment and facilitate the
      development and spread of resistance in critical species of bacteria including
      pathogens. Methanogenesis, nitrogen transformation and sulphate reduction are
      among the key ecosystem processes performed by bacteria in nature that can also
      be affected by the impacts of environmental contamination by antibiotics.
      Together, the effects of the development of resistance in bacteria involved in
      maintaining overall ecosystem health and the development of resistance in human,
      animal and fish pathogens, make serious contributions to the risks associated
      with environmental pollution by antibiotics. In this brief review, we discuss the
      multiple impacts on human and ecosystem health of environmental contamination by
      antibiotic compounds. 

PMID- 27029299
TI  - Rifampicin Resistance: Fitness Costs and the Significance of Compensatory
      Evolution.
AB  - Seventy years after the introduction of antibiotic chemotherapy to treat
      tuberculosis, problems caused by drug-resistance in Mycobacterium tuberculosis
      have become greater than ever. The discovery and development of novel drugs and
      drug combination therapies will be critical to managing these problematic
      infections. However, to maintain effective therapy in the long-term and to avoid
      repeating the mistakes of the past, it is essential that we understand how
      resistance to antibiotics evolves in M. tuberculosis. Recent studies in genomics
      and genetics, employing both clinical isolates and model organisms, have revealed
      that resistance to the frontline anti-tuberculosis drug, rifampicin, is very
      strongly associated with the selection of fitness compensatory mutations in the
      different subunits of RNA polymerase. This mode of resistance evolution may also
      apply to other drugs, and knowledge of the rates and mechanisms could be used to
      design improved diagnostics and by tracking the evolution of infectious strains,
      to inform the optimization of therapies. 

PMID- 27029300
TI  - Molecular Mechanisms and Clinical Impact of Acquired and Intrinsic Fosfomycin
      Resistance.
AB  - Bacterial infections caused by antibiotic-resistant isolates have become a major
      health problem in recent years, since they are very difficult to treat, leading
      to an increase in morbidity and mortality. Fosfomycin is a broad-spectrum
      bactericidal antibiotic that inhibits cell wall biosynthesis in both Gram
      negative and Gram-positive bacteria. This antibiotic has a unique mechanism of
      action and inhibits the initial step in peptidoglycan biosynthesis by blocking
      the enzyme, MurA. Fosfomycin has been used successfully for the treatment of
      urinary tract infections for a long time, but the increased emergence of
      antibiotic resistance has made fosfomycin a suitable candidate for the treatment
      of infections caused by multidrug-resistant pathogens, especially in combination
      with other therapeutic partners. The acquisition of fosfomycin resistance could
      threaten the reintroduction of this antibiotic for the treatment of bacterial
      infection. Here, we analyse the mechanism of action and molecular mechanisms for
      the development of fosfomycin resistance, including the modification of the
      antibiotic target, reduced antibiotic uptake and antibiotic inactivation. In
      addition, we describe the role of each pathway in clinical isolates. 

PMID- 27029302
TI  - The Economic Impact of Starting, Stopping, and Restarting an Antibiotic
      Stewardship Program: A 14-Year Experience.
AB  - Regions Hospital started a multidisciplinary antibiotic stewardship program (ASP)
      in 1998. The program effectively shut down from 2002-2004 as key personnel
      departed and was then restarted but without the dedicated pharmacist and
      infectious diseases physician. Purchasing data (in dollars or
      dollars/patient/day) unadjusted for inflation served as a surrogate marker of
      antibiotic consumption. These data were reviewed monthly, quarterly, and yearly
      along with antibiotic susceptibility patterns on a semi-annual basis. Segmented
      regression analysis was use to compare restricted antibiotic purchases for
      performance periods of 1998-2001 (construction), 2002-2004 (de-construction), and
      2005-2011 (reconstruction). After 4 years (1998-2001) of operation, a number of
      key participants of the ASP departed. For the following three years (2002-2004)
      the intensity and focus of the program floundered. This trend was averted when
      the program was revitalized in early 2005. The construction, deconstruction, and
      reconstruction of our ASP provided a unique opportunity to statistically examine
      the financial impact of our ASP or lack thereof in the same institution. We
      demonstrate a significant economic impact during ASP deconstruction and
      reconstruction. 

PMID- 27029301
TI  - Phenotypic Resistance to Antibiotics.
AB  - The development of antibiotic resistance is usually associated with genetic
      changes, either to the acquisition of resistance genes, or to mutations in
      elements relevant for the activity of the antibiotic. However, in some situations
      resistance can be achieved without any genetic alteration; this is called
      phenotypic resistance. Non-inherited resistance is associated to specific
      processes such as growth in biofilms, a stationary growth phase or persistence.
      These situations might occur during infection but they are not usually considered
      in classical susceptibility tests at the clinical microbiology laboratories.
      Recent work has also shown that the susceptibility to antibiotics is highly
      dependent on the bacterial metabolism and that global metabolic regulators can
      modulate this phenotype. This modulation includes situations in which bacteria
      can be more resistant or more susceptible to antibiotics. Understanding these
      processes will thus help in establishing novel therapeutic approaches based on
      the actual susceptibility shown by bacteria during infection, which might differ
      from that determined in the laboratory. In this review, we discuss different
      examples of phenotypic resistance and the mechanisms that regulate the crosstalk
      between bacterial metabolism and the susceptibility to antibiotics. Finally,
      information on strategies currently under development for diminishing the
      phenotypic resistance to antibiotics of bacterial pathogens is presented. 

PMID- 27029303
TI  - The Effects of Two Novel Copper-Based Formulations on Helicobacter pylori.
AB  - We investigated the effects of two novel copper-based inorganic formulations for
      their activity against 60 isolates of Helicobacter pylori (Hp). The two copper
      based formulations were tested against three NCTC Helicobacter pylori isolates
      and 57 clinical strains isolated from the UK and Italy in time-kill assays. Both
      copper-based formulations were bio-cidal against all Helicobacter pylori strains
      tested reducing the viable count by 4-5 log within 2 h. These two copper-based
      anti-microbial agents deserve further study in relation to the treatment of H.
      pylori-related gastric disease. 

PMID- 27029304
TI  - Assessment of the Presence of Pharmaceutical Compounds in Seawater Samples from
      Coastal Area of Gran Canaria Island (Spain).
AB  - This study presents the evaluation of seven pharmaceutical compounds belonging to
      different commonly used therapeutic classes in seawater samples from coastal
      areas of Gran Canaria Island. The target compounds include atenolol
      (antihypertensive), acetaminophen (analgesic), norfloxacin and ciprofloxacin
      (antibiotics), carbamazepine (antiepileptic) and ketoprofen and diclofenac (anti
      inflammatory). Solid phase extraction (SPE) was used for the extraction and
      preconcentration of the samples, and liquid chromatography tandem mass
      spectrometry (LC-MS/MS) was used for the determination of the compounds. Under
      optimal conditions, the recoveries obtained were in the range of 78.3% to 98.2%,
      and the relative standard deviations were less than 11.8%. The detection and
      quantification limits of the method were in the ranges of 0.1-2.8 and 0.3-9.3
      ng.L(-1), respectively. The developed method was applied to evaluate the presence
      of these pharmaceutical compounds in seawater from four outfalls in Gran Canaria
      Island (Spain) during one year. Ciprofloxacin and norfloxacin were found in a
      large number of samples in a concentration range of 9.0-3551.7 ng.L(-1). Low
      levels of diclofenac, acetaminophen and ketoprofen were found sporadically. 

PMID- 27029306
TI  - Exploratory Spatial Mapping of the Occurrence of Antimicrobial Resistance in E.
      coli in the Community.
AB  - The use of antimicrobials over the past six decades has been associated with the
      emergence and dissemination of antimicrobial-resistant bacteria. To explore local
      geographical patterns in the occurrence of acquired antimicrobial resistance
      (AMR), AMR of E. coli causing urinary tract infections (UTI) in the community in
      the West of Ireland was mapped. All adult patients consulting with a suspected
      UTI in 22 general practices in the West of Ireland over a nine-month study period
      were requested to supply a urine sample. Those with a laboratory confirmed E.
      coli infection were included (n = 752) in the study. Antimicrobial susceptibility
      testing was performed by standardized disc diffusion. Patient addresses were
      geocoded. The diameters of the zone of inhibition of growth for trimethoprim (5
      MUg) and ciprofloxacin (5 MUg) for the relevant isolate was mapped against the
      patient address using ArcGIS software. A series of maps illustrating spatial
      distribution of AMR in the West of Ireland were generated. The spatial data
      demonstrated a higher proportion of isolates with AMR from urban areas. Some
      rural areas also showed high levels of resistant E. coli. Our study is the first
      to demonstrate the feasibility of using a geographical information system (GIS)
      platform for routine visual geographical analysis of AMR data in Ireland. Routine
      presentation of AMR data in this format may be valuable in understanding AMR
      trends at a local level. 

PMID- 27029307
TI  - Empirical Antibiotic Therapy for Ventilator-Associated Pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is the most common infectious complication
      in the intensive care unit. It can increase duration of mechanical ventilation,
      length of stay, costs, and mortality. Improvements in the administration of
      empirical antibiotic therapy have potential to reduce the complications of VAP.
      This review will discuss the current data addressing empirical antibiotic therapy
      and the effect on mortality in patients with VAP. It will also address factors
      that could improve the administration of empirical antibiotics and directions for
      future research. 

PMID- 27029305
TI  - Multiple Pathways of Genome Plasticity Leading to Development of Antibiotic
      Resistance.
AB  - The emergence of multi-resistant bacterial strains is a major source of concern
      and has been correlated with the widespread use of antibiotics. The origins of
      resistance are intensively studied and many mechanisms involved in resistance
      have been identified, such as exogenous gene acquisition by horizontal gene
      transfer (HGT), mutations in the targeted functions, and more recently,
      antibiotic tolerance through persistence. In this review, we focus on factors
      leading to integron rearrangements and gene capture facilitating antibiotic
      resistance acquisition, maintenance and spread. The role of stress responses,
      such as the SOS response, is discussed. 

PMID- 27029308
TI  - Occurrence and Distribution of Synthetic Organic Substances in Boreal Coniferous
      Forest Soils Fertilized with Hygienized Municipal Sewage Sludge.
AB  - The occurrence and distribution of synthetic organic substances following
      application of dried and granulated (hygienized) municipal sewage sludge in
      Swedish boreal coniferous forests were investigated. Elevated concentrations of
      triclosan (TCS), polybrominated diphenyl ethers (PBDEs), and polychlorinated
      biphenyls (PCBs) were detected in the humus layer. Concentrations of ethinyl
      estradiol (EE2), norfloxacin, ciprofloxacin, ofloxacin (FQs), and polyaromatic
      hydrocarbons (PAHs) were not significantly influenced. Maximum concentrations in
      humus were as follows (in ng/g dry matter): TCS; 778; PBDEs; 25; and PCB7; 16.7.
      Fertilization did not alter the levels of the substances in mineral soil, ground
      water, and various types of samples related to air. Further research within this
      area is needed, including ecotoxicological effects and fate, in order to improve
      the knowledge regarding the use of sludge as a fertilizing agent. Continuous
      annual monitoring, with respect to sampling and analysis, should be conducted on
      the already-fertilized fields. 

PMID- 27029309
TI  - Environmental and Public Health Implications of Water Reuse: Antibiotics,
      Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes.
AB  - Water scarcity is a global problem, and is particularly acute in certain regions
      like Africa, the Middle East, as well as the western states of America. A
      breakdown on water usage revealed that 70% of freshwater supplies are used for
      agricultural irrigation. The use of reclaimed water as an alternative water
      source for agricultural irrigation would greatly alleviate the demand on
      freshwater sources. This paradigm shift is gaining momentum in several water
      scarce countries like Saudi Arabia. However, microbial problems associated with
      reclaimed water may hinder the use of reclaimed water for agricultural
      irrigation. Of particular concern is that the occurrence of antibiotic residues
      in the reclaimed water can select for antibiotic resistance genes among the
      microbial community. Antibiotic resistance genes can be associated with mobile
      genetic elements, which in turn allow a promiscuous transfer of resistance traits
      from one bacterium to another. Together with the pathogens that are present in
      the reclaimed water, antibiotic resistant bacteria can potentially exchange
      mobile genetic elements to create the "perfect microbial storm". Given the
      significance of this issue, a deeper understanding of the occurrence of
      antibiotics in reclaimed water, and their potential influence on the selection of
      resistant microorganisms would be essential. In this review paper, we collated
      literature over the past two decades to determine the occurrence of antibiotics
      in municipal wastewater and livestock manure. We then discuss how these
      antibiotic resistant bacteria may impose a potential microbial risk to the
      environment and public health, and the knowledge gaps that would have to be
      addressed in future studies. Overall, the collation of the literature in
      wastewater treatment and agriculture serves to frame and identify potential
      concerns with respect to antibiotics, antibiotic resistant bacteria, and
      antibiotic resistance genes in reclaimed water. 

PMID- 27029310
TI  - Antimicrobial Stewardship: The Need to Cover All Bases.
AB  - Increasing antimicrobial resistance has necessitated an approach to guide the use
      of antibiotics. The necessity to guide antimicrobial use via stewardship has
      never been more urgent. The decline in anti-infective innovation and the failure
      of currently available antimicrobials to treat some serious infections forces
      clinicians to change those behaviors that drive antimicrobial resistance. The
      majority of antimicrobial stewardship (AMS) programs function in acute-care
      hospitals, however, hospitals are only one setting where antibiotics are
      prescribed. Antimicrobial use is also high in residential aged care facilities
      and in the community. Prescribing in aged care is influenced by the fact that
      elderly residents have lowered immunity, are susceptible to infection and are
      frequently colonized with multi-resistant organisms. While in the community,
      prescribers are faced with public misconceptions about the effectiveness of
      antibiotics for many upper respiratory tract illnesses. AMS programs in all of
      these locations must be sustainable over a long period of time in order to be
      effective. A future with effective antimicrobials to treat bacterial infection
      will depend on AMS covering all of these bases. This review discusses AMS in
      acute care hospitals, aged care and the community and emphasizes that AMS is
      critical to patient safety and relies on government, clinician and community
      engagement. 

PMID- 27029311
TI  - Designing Safer and Greener Antibiotics.
AB  - Since the production of the first pharmaceutically active molecules at the
      beginning of the 1900s, drug molecules and their metabolites have been observed
      in the environment in significant concentrations. In this review, the persistence
      of antibiotics in the environment and their associated effects on ecosystems,
      bacterial resistance and health effects will be examined. Solutions to these
      problems will also be discussed, including the pharmaceutical industries input,
      green chemistry, computer modeling and representative ionic liquid research. 

PMID- 27029312
TI  - "How Do You Feel about Antibiotics for This?" A Qualitative Study of Physician
      Attitudes towards a Context-Rich Communication Skills Method.
AB  - To explore experiences with and views of general practitioners (GPs) on a
      physician communication training method in primary care and its applicability and
      implementation in daily practice, we performed a semi-structured qualitative
      study of GPs' experience of training in and implementing a communication skills
      training program for managing lower respiratory tract infection (LRTI) which
      included a seminar, simulated patient consultation together with providing and
      receiving feedback on ones own transcript, and a seminar in a structured approach
      to the LRTI consultation. Seventeen out of 20 eligible GPs who had participated
      in the IMPAC3T trial and were allocated to receiving enhanced physician
      communication training for managing lower respiratory tract infection
      participated. GPs' experiences with the physician communication training method
      and its specific components were positive. The method gave GPs additional tools
      for managing LRTI consultations and increased their sense of providing evidence
      based management. During the study, GPs reported using almost all communication
      items covered in the training, but some GPs stated that the communication skills
      diluted over time, and that they continued to use a selected set of the skills.
      The general communication items were most regularly used. Implementation of the
      method in daily practice helped GPs to prescribe fewer antibiotics in LRTI with
      the only perceived disadvantage being time-pressure. This study suggests that GPs
      felt positive about the physician communication training method for enhanced
      management of LRTI in primary care. GPs continued to use some of the
      communication items, of which general communication items were the most common.
      Furthermore, GPs believed that implementation of the communication skills in
      daily practice helped them to prescribe fewer antibiotics. The context-rich
      communication method could have wider application in common conditions in primary
      care. 

PMID- 27029313
TI  - Antibiotic Usage Prior and During Hospitalization for Clinical Severe Pneumonia
      in Children under Five Years of Age in Rabat, Morocco.
AB  - Scarce and limited epidemiological, clinical and microbiological data are
      available regarding pediatric respiratory tract infections in the Kingdom of
      Morocco, a middle-income country in Northwestern Africa. Data on antibiotic usage
      for such infections are also scarce. A good understanding of pre-admission and
      intra-hospital usage of antibiotics in children with respiratory infections
      linked with an adequate surveillance of the antibiotic susceptibility from
      circulating pathogens could help policy makers improve their recommendations on
      management of respiratory infections. We hereby present data on antibiotic usage
      prior and during admission and antibiotic susceptibility of major circulating
      respiratory pathogens in children under five years of age admitted to the Hopital
      d'Enfants de Rabat, Morocco, with a diagnosis of clinical severe pneumonia (using
      World Health Organization (WHO) standardized case definitions) during a period of
      14 months (November 2010-December 2011), as part of a larger hospital-based
      surveillance study designed to understand the etiology and epidemiology of severe
      pneumonia cases among children. 

PMID- 27029314
TI  - Public Beliefs about Antibiotics, Infection and Resistance: A Qualitative Study.
AB  - We aimed to gain an in-depth understanding of public views and ways of talking
      about antibiotics. Four focus groups were held with members of the public. In
      addition, 39 households were recruited and interviews, diaries of medicine
      taking, diaries of any contact with medication were used to explore understanding
      and use of medication. Discussions related to antibiotics were identified and
      analyzed. Participants in this study were worried about adverse effects of
      antibiotics, particularly for recurrent infections. Some were concerned that
      antibiotics upset the body's "balance", and many used strategies to try to
      prevent and treat infections without antibiotics. They rarely used military
      metaphors about infection (e.g., describing bacteria as invading armies) but
      instead spoke of clearing infections. They had little understanding of the
      concept of antibiotic resistance but they thought that over-using antibiotics was
      unwise because it would reduce their future effectiveness. Previous studies tend
      to focus on problems such as lack of knowledge, or belief in the curative powers
      of antibiotics for viral illness, and neglect the concerns that people have about
      antibiotics, and the fact that many people try to avoid them. We suggest that
      these concerns about antibiotics form a resource for educating patients, for
      health promotion and social marketing strategies. 

PMID- 27029315
TI  - Low Request of Antibiotics from Patients with Respiratory Tract Infections in Six
      Countries: Results from the Happy Audit Study.
AB  - A total of 59,535 patients with respiratory tract infections were registered in
      the Happy Audit project, an audit-based, before-and-after study conducted in
      primary care centres of six countries (Argentina, Denmark, Lithuania, Russia,
      Spain, and Sweden) in 2008 and 2009. An antibiotic was explicitly requested by
      the patient in 1,255 cases (2.1%), with a great variation across countries
      ranging from 0.4%-4.9%. Antibiotics were significantly more often prescribed to
      patients requesting them compared to those who did not (64% vs. 28%; p < 0.001).
      Patients with acute exacerbations of chronic bronchitis/chronic obstructive
      pulmonary disease were most likely to request antibiotics while those with common
      colds were least likely (3.9% vs. 1.2%, respectively). The presence of tonsillar
      exudates and dyspnoea were more commonly associated with a demand for
      antibiotics. Even though physicians very often perceive that patients demand an
      antibiotic, the results of this study clearly show that patients only request
      antibiotics in a low percentage of cases. Patients were most likely to request
      antibiotics when they had symptoms of lower respiratory tract infections and when
      they came with more severe symptoms. Furthermore, there were considerable
      differences between countries, suggesting that the different backgrounds and
      traditions largely explain this variability in patients' requests for
      antibiotics. 

PMID- 27029316
TI  - Influence of Sterilized Human Fecal Extract on the Sensitivity of Salmonella
      enterica ATCC 13076 and Listeria monocytogenes ATCC 15313 to Enrofloxacin.
AB  - There is much debate on whether continuous exposure of commensal bacteria and
      potential pathogens residing in the human intestinal tract to low levels of
      antimicrobial agents from treated food animals pose a public health concern. To
      investigate antimicrobial effects on bacteria under colonic conditions, we
      studied resistance development in Salmonella enterica and Listeria monocytogenes
      exposed to enrofloxacin in the presence of fecal extract. The bacteria were
      incubated at 37  degrees C in Mueller-Hinton broth, with and without 0.01~0.5
      MUg/mL enrofloxacin, in the presence and absence of sucrose, and with 1% or 2.5%
      filter-sterilized fecal extract, for three passages. In the second and third
      passages, only the bacteria incubated in the media containing sterilized fecal
      extract grew in 0.5 MUg/mL of enrofloxacin. Fecal extract (1% and 2.5%) decreased
      the sensitivity of S. enterica to enrofloxacin in the medium containing the
      efflux pump inhibitors reserpine and carbonyl cyanide-m-chlorophenylhydrazone
      (CCCP) and affected the accumulation of ethidium bromide (EtBr) in this
      bacterium. Enrofloxacin (0.06 ug/mL) and fecal extract altered the composition of
      fatty acids in S. enterica and L. monocytogenes. We conclude that fecal extract
      decreased the susceptibilities of S. enterica and L. monocytogenes to
      concentrations of enrofloxacin higher than the MIC and resulted in rapid
      resistance selection. 

PMID- 27029317
TI  - Pipeline of Known Chemical Classes of Antibiotics.
AB  - Many approaches are used to discover new antibiotic compounds, one of the most
      widespread being the chemical modification of known antibiotics. This type of
      discovery has been so important in the development of new antibiotics that most
      antibiotics used today belong to the same chemical classes as antibiotics
      discovered in the 1950s and 1960s. Even though the discovery of new classes of
      antibiotics is urgently needed, the chemical modification of antibiotics in known
      classes is still widely used to discover new antibiotics, resulting in a great
      number of compounds in the discovery and clinical pipeline that belong to
      existing classes. In this scenario, the present article presents an overview of
      the R&D pipeline of new antibiotics in known classes of antibiotics, from
      discovery to clinical trial, in order to map out the technological trends in this
      type of antibiotic R&D, aiming to identify the chemical classes attracting most
      interest, their spectrum of activity, and the new subclasses under development.
      The result of the study shows that the new antibiotics in the pipeline belong to
      the following chemical classes: quinolones, aminoglycosides, macrolides,
      oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides,
      polymyxins and cyclic lipopeptides. 

PMID- 27029318
TI  - Molecular, dynamic, and structural origin of inhomogeneous magnetization transfer
      in lipid membranes.
AB  - PURPOSE: To elucidate the dynamic, structural, and molecular properties that
      create inhomogeneous magnetization transfer (ihMT) contrast. METHODS: Amphiphilic
      lipids, lamellar phospholipids with cholesterol, and bovine spinal cord (BSC)
      specimens were examined along with nonlipid systems. Magnetization transfer (MT),
      enhanced MT (eMT, obtained with double-sided radiofrequency saturation), ihMT (MT
      - eMT), and dipolar relaxation, T1D , were measured at 2.0 and 11.7 T. RESULTS:
      The amplitude of ihMT ratio (ihMTR) is positively correlated with T1D values.
      Both ihMTR and T1D increase with increasing temperature in BSC white matter and
      in phospholipids and decrease with temperature in other lipids. Changes in ihMTR
      with temperature arise primarily from alterations in MT rather than eMT. Spectral
      width of MT, eMT, and ihMT increases with increasing carbon chain length.
      CONCLUSIONS: Concerted motions of phospholipids in white matter decrease proton
      spin diffusion leading to increased proton T1D times and increased ihMT
      amplitudes, consistent with decoupling of Zeeman and dipolar spin reservoirs.
      Molecular specificity and dynamic sensitivity of ihMT contrast make it a suitable
      candidate for probing myelin membrane disorders. Magn Reson Med 77:1318-1328,
      2017. (c) 2016 International Society for Magnetic Resonance in Medicine.

PMID- 27029319
TI  - Landscape of genomic diversity and trait discovery in soybean.
AB  - Cultivated soybean [Glycine max (L.) Merr.] is a primary source of vegetable oil
      and protein. We report a landscape analysis of genome-wide genetic variation and
      an association study of major domestication and agronomic traits in soybean. A
      total of 106 soybean genomes representing wild, landraces, and elite lines were
      re-sequenced at an average of 17x depth with a 97.5% coverage. Over 10 million
      high-quality SNPs were discovered, and 35.34% of these have not been previously
      reported. Additionally, 159 putative domestication sweeps were identified, which
      includes 54.34 Mbp (4.9%) and 4,414 genes; 146 regions were involved in
      artificial selection during domestication. A genome-wide association study of
      major traits including oil and protein content, salinity, and domestication
      traits resulted in the discovery of novel alleles. Genomic information from this
      study provides a valuable resource for understanding soybean genome structure and
      evolution, and can also facilitate trait dissection leading to sequencing-based
      molecular breeding. 

PMID- 27029320
TI  - Riboflavin and health: A review of recent human research.
AB  - There has lately been a renewed interest in Riboflavin owing to insight into its
      recognition as an essential component of cellular biochemistry. The knowledge of
      the mechanisms and regulation of intestinal absorption of riboflavin and its
      health implications has significantly been expanded in recent years. The purpose
      of this review is to provide an overview of the importance of riboflavin, its
      absorption and metabolism in health and diseased conditions, its deficiency and
      its association with various health diseases, and metabolic disorders. Efforts
      have been made to review the available information in literature on the
      relationship between riboflavin and various clinical abnormalities. The role of
      riboflavin has also been dealt in the prevention of a wide array of health
      diseases like migraine, anemia, cancer, hyperglycemia, hypertension, diabetes
      mellitus, and oxidative stress directly or indirectly. The riboflavin deficiency
      has profound effect on iron absorption, metabolism of tryptophan, mitochondrial
      dysfunction, gastrointestinal tract, brain dysfunction, and metabolism of other
      vitamins as well as is associated with skin disorders. Toxicological and
      photosensitizing properties of riboflavin make it suitable for biological use,
      such as virus inactivation, excellent photosensitizer, and promising adjuvant in
      chemo radiotherapy in cancer treatment. A number of recent studies have indicated
      and highlighted the cellular processes and biological effects associated with
      riboflavin supplementation in metabolic diseases. Overall, a deeper understanding
      of these emerging roles of riboflavin intake is essential to design better
      therapies for future.

PMID- 27029321
TI  - Henoch-Schonlein purpura with joint involvement: Analysis of 71 cases.
AB  - BACKGROUND: Although joint involvement is the second most common clinical
      manifestation after skin involvement in patients with Henoch-Schonlein purpura
      (HSP), it has not been well characterized. The aim of this study was to profile
      the clinical characteristics and identify the potential risk factors for kidney
      damage in HSP patients having joint involvement. METHODS: We retrospectively
      reviewed 71 cases of HSP patients with joint involvement who attended our
      hospital between January 2010 and March 2012 and analyzed their epidemiological
      profile, clinical characteristics, follow-up findings (up to three years) and
      overall prognosis. Logistic regression analysis was performed to identify risk
      factors associated with renal symptoms in HSP patients with joint involvement.
      RESULTS: Average age of patients was 8.55 +/- 2.13 years with male to female
      ratio at 1.29:1. The peak age of disease onset was six to 11 years. The most
      common triggers included upper respiratory infection, vigorous physical activity,
      and autumn and winter seasons. Forty cases (56.35 %) had gastrointestinal
      involvement and 37 (52.11 %) had kidney damage; gastrointestinal system, scrotal
      involvement, and increased D-dimer levels were significantly associated with
      kidney injury (P < 0.05) by multivariate analysis. Glucocorticoid therapy was
      effective in alleviating symptoms. CONCLUSION: Gastrointestinal symptoms, scrotal
      involvement, and increased D-dimer are the potential risk factors for kidney
      damage in HSP patients having joint involvement. Rational use of corticosteroids
      was probably responsible for the good clinical outcomes.

PMID- 27029322
TI  - Research on Effective Oxygen Window Influencing the Capacity of Li-O2 Batteries.
AB  - Li-O2 batteries have attracted extensive attention recently due to the extremely
      huge specific energy. Similar to research mode of Li-ion batteries, nowadays
      specific capacity based on the mass of cathode material is widely adopted to
      evaluate the electrochemical performance of Li-O2 batteries. However, the
      prerequisite of linear correlation between the delivered capacity and active mass
      is easily neglected. In this paper, we demonstrate the rationality of specific
      capacity adopted in Li-ion batteries with classic LiCoO2 cathode by confirming
      the linear correlation between cell capacity and LiCoO2 mass. Delivered
      capacities of Li-O2 batteries with different cathode masses are simultaneously
      measured and nonlinear correlation is obtained. The discharge and charge products
      are identified by X-ray diffraction and in situ gas chromatography-mass
      spectrometry analysis to ensure reaction mechanism. Discharge capacities of Li-O2
      batteries with various areas of oxygen window are further studied, which shows
      that cell capacity increases linearly with the area of oxygen window. Scanning
      electron microscopy is employed to observe the discharged electrode and shows
      that Li2O2 deposition during discharge mainly occurs in the electrode area
      exposure to the oxygen, which is consequently defined as effective area for
      accommodating Li2O2. Moreover, a plausible route for formation of effective area
      in the oxygen electrode is proposed. These results provide evidence that
      effective area is an equally important factor determining cell capacity.

PMID- 27029324
TI  - Can the Social Vulnerability Index Be Used for More Than Emergency Preparedness?
      An Examination Using Youth Physical Fitness Data.
AB  - BACKGROUND: The Social Vulnerability Index (SVI), a publicly available dataset,
      is used in emergency preparedness to identify communities in greatest need of
      resources. The SVI includes multiple socioeconomic, demographic, and geographic
      indicators that also are associated with physical fitness and physical activity.
      This study examined the utility of using the SVI to explain variation in youth
      fitness, including aerobic capacity and body mass index. METHODS: FITNESSGRAM
      data from 2,126 Georgia schools were matched at the census tract level with SVI
      themes of socioeconomic, household composition, minority status and language, and
      housing and transportation. Multivariate multiple regression models were used to
      test whether SVI factors explained fitness outcomes, controlling for grade level
      (ie, elementary, middle, high school) and stratified by gender. RESULTS: SVI
      themes explained the most variation in aerobic fitness and body mass index for
      both boys and girls (R2 values 11.5% to 26.6%). Socioeconomic, Minority Status
      and Language, and Housing and Transportation themes were salient predictors of
      fitness outcomes. CONCLUSIONS: Youth fitness in Georgia was related to
      socioeconomic, demographic, and geographic themes. The SVI may be a useful needs
      assessment tool for health officials and researchers examining multilevel
      influences on health behaviors or identifying communities for prevention efforts.

PMID- 27029323
TI  - Characterization of DNA topoisomerase I in three SN-38 resistant human colon
      cancer cell lines reveals a new pair of resistance-associated mutations.
AB  - BACKGROUND: DNA topoisomerase I (Top1) is a DNA unwinding protein and the
      specific target of the camptothecin class of chemotherapeutic drugs. One of
      these, irinotecan, acting through its active metabolite SN-38, is used in the
      treatment of metastatic colorectal cancer. However, resistance to irinotecan
      represents a major clinical problem. Since molecular alterations in Top1 may
      result in resistance to irinotecan, we characterized Top1 in three human colon
      cancer cell lines with acquired resistance to SN-38. METHODS: Three SN-38
      resistant (20-67 fold increased resistance) cell lines were generated and
      compared to wild-type parental cells with regards to: TOP1 gene copy number and
      gene sequence, Top1 expression (mRNA and protein), Top1 enzymatic activity in the
      absence and presence of drug, and Top1-DNA cleavage complexes in drug treated
      cells. TOP1 mutations were validated by PCR using mutant specific primers.
      Furthermore, cross-resistance to two indenoisoquinoline Top1-targeting drugs (NSC
      725776 and NSC 743400) and two Top2-targeting drugs (epirubicin and etoposide)
      was investigated. RESULTS: Two of three SN-38 resistant cell lines carried TOP1
      gene copy number aberrations: A TOP1 gene copy gain and a loss of chromosome 20,
      respectively. One resistant cell line harbored a pair of yet unreported TOP1
      mutations (R364K and G717R) in close proximity to the drug binding site. Mutant
      TOP1 was expressed at a markedly higher level than wild-type TOP1. None or very
      small reductions were observed in Top1 expression or Top1 activity in the absence
      of drug. In all three SN-38 resistant cell lines Top1 activity was maintained in
      the presence of high concentrations of SN-38. None or only partial cross
      resistance were observed for etoposide and epirubicin, respectively. SN-38
      resistant cells with wild-type TOP1 remained sensitive to NSC 743400, while cells
      with mutant TOP1 was fully cross-resistant to both indenoisoquinolines. Top1-DNA
      cleavage complex formation following drug treatment supported the other findings.
      CONCLUSIONS: This study adds to the growing knowledge about resistance mechanisms
      for Top1-targeting chemotherapeutic drugs. Importantly, two yet unreported TOP1
      mutations were identified, and it was underlined that cross-resistance to the new
      indenoisoquinoline drugs depends on the specific underlying molecular mechanism
      of resistance to SN-38.

PMID- 27029325
TI  - On Your Mark, Get Set, Go: Levels of Physical Activity in the Kingdom of Saudi
      Arabia, 2013.
AB  - BACKGROUND: With the lack of appropriate data, we conducted a large household
      survey in 2013 to determine current rates of physical activity in the Kingdom of
      Saudi Arabia (KSA). METHODS: The Saudi Health Interview Survey is a national
      multistage survey of individuals aged 15 years or older. We used a multivariate
      logistic regression model to measure association between sociodemographic and
      selected characteristics and meeting the recommended levels of moderate and
      vigorous weekly physical activity. RESULTS: Of a total of 12,000 households
      contacted, 10,735 (89.4%) participants completed Saudi Health Interview Survey.
      An estimated 4.5 million (34.5%) Saudis aged 15 years or older reported no weekly
      physical activity, while only 1.7 million (12.9%) meet the recommended levels of
      moderate physical activity (MPA). The likelihood of meeting MPA decreased with
      age, education, among women, those with a history of diagnosis of select chronic
      conditions, including diabetes. Similar results were found for the likelihood of
      meeting the recommended levels of vigorous weekly physical activity. CONCLUSIONS:
      We found very low levels of physical activity in KSA. Perhaps, KSA can challenge
      communities or employers to devise solutions and reward those with the best
      results. These solutions would be of great value to other Gulf countries, as
      well.

PMID- 27029327
TI  - [Diffusion tensor imaging tractography and intraoperative neurophysiological
      monitoring in surgery of intracranial tumors located near the pyramidal tract].
AB  - BACKGROUND: Practical application of methods for intravital examination of the
      brain pathways, such as preoperative diffusion tensor imaging (DTI) tractography
      and intraoperative neurophysiological monitoring, facilitates safer resection of
      intracranial tumors located near the pyramidal tracts (PTs). PURPOSE: The study
      purpose was to investigate the relationships between intracerebral tumors of
      different histological nature and the pyramidal tract based on preoperative DTI
      tractography and various methods of intraoperative neurophysiological monitoring
      for intraoperative identification of the pyramidal tract, depending on different
      variants of the topographo-anatomic relationships between the pyramidal fascicle
      and the tumor. MATERIAL AND METHODS: The study included 29 patients with
      supratentorial tumors of a different histological structure. Of these, 2 patients
      had grade I tumors, 8 patients had grade II tumors, 4 patients had grade III
      tumors, 11 patients grade IV tumors, and 4 patients had brain metastases. The
      patients underwent preoperative DTI tractography with PT reconstruction and
      evaluation of the topographo-anatomic relationships between the pyramidal tract
      and the tumor (tract: intact, infiltrated, displaced). Neurophysiological
      monitoring (direct electrical stimulation in 24 patients and transcranial motor
      evoked potentials in 26 patients) was used during surgery. The strength of
      stimulating current for direct stimulation was varied from 10 to 30 mA.
      Postoperatively, the motor function was evaluated by using a 5-score scale, and
      the data were compared to the preoperative data. RESULTS: According to
      preoperative DTI tractography in patients with grade I-II gliomas, the
      corticospinal tracts were infiltrated in 2 cases, displaced in 3 cases, and
      intact in 5 cases. In patients with grade III-IV gliomas and metastases, the
      tracts were infiltrated in 8 cases, displaced in 4 cases, and intact in 7 cases.
      Motor responses evoked by direct electrical stimulation were obtained in 5 out of
      6 patients with the pyramidal tract displaced by the tumor and in 7 out of 8
      patients with the tract infiltrated by the tumor. In the case of the intact
      tract, the PT to tumor distance and the stimulus strength play an important role:
      responses were obtained in 4 out of 10 patients. In the case of transcranial
      motor evoked potentials (TCMEPs), no dynamics of the potential amplitude was
      detected in 17 out of 26 patients during surgery; a reduced TCMEP amplitude was
      detected in 9 patients. CONCLUSION: 1. Patients with an infiltrated or displaced
      pyramidal tract had significantly more often hemiparesis before surgery and
      aggravation of hemiparesis after the surgery compared to patients with an intact
      tract. 2. In the case of direct electrical stimulation of the PT, motor responses
      (according to preoperative DTI tractography) were significantly more often
      observed for the pyramidal tract infiltrated and displaced by the tumor. 3. A
      reduction in the motor neurologic deficit in the postoperative period was
      significantly more often observed for application of a larger current strength
      during direct electrical stimulation. 4. Persistence of the TCMEP amplitude
      during surgery is a reliable predictor for no aggravation of the motor
      neurological deficit after surgery. Postoperative aggravation of hemiparesis was
      significantly more often observed when TC MEPs decreased during surgery.

PMID- 27029328
TI  - [A telescopic vertebral endoprosthesis for subaxial cervical fusion].
AB  - PURPOSE: The study purpose was to develop an anterior subaxial cervical fusion
      technique using a new telescopic vertebral graft (VG) construction and to
      introduce the technique into clinical practice. MATERIAL AND METHODS: We analyzed
      existing VG constructions used in anterior interbody fusion at the cervical spine
      level and developed our own variant of a vertical, cylindrical, telescopic, mesh,
      vertebral endoprosthesis as well as a technique of its placement to replace
      bodies of the cervical vertebrae. The technique was used in 11 patients with
      spinal trauma. The orthopedic and neurological status and outcomes of surgical
      treatment were assessed using ASIA/IMSOP, Odom, and VAS scales. RESULTS AND
      DISCUSSION: The first cases of replacement of a resected vertebra by the proposed
      construction indicate the advisability of using this VG to restore the sagittal
      profile, stabilize the operated spinal motion segment, and create conditions for
      the formation of an adequate supporting bone block. The graft construction can be
      filled with a significant amount of a filler and makes it possible to add and
      tighten the filler after placing the graft into the operating position. The study
      demonstrated the construct efficacy. No postoperative complications associated
      with the use and placement of the telescopic constructions was observed.

PMID- 27029326
TI  - Increases in ambient particulate matter air pollution, acute changes in platelet
      function, and effect modification by aspirin and omega-3 fatty acids: A panel
      study.
AB  - Increased particulate matter (PM) air pollutant concentrations have been
      associated with platelet activation. It was postulated that elevated air
      pollutant concentrations would be associated with increases in measures of
      platelet function and that responses would be blunted when taking aspirin and/or
      fish oil. Data from a sequential therapy trial (30 subjects with type 2 diabetes
      mellitus), with 4 clinic visits (first: no supplements, second: aspirin, third:
      omega-3 fatty acid supplements, fourth: aspirin and omega-3 fatty acids) per
      subject, were utilized. Using linear mixed models, adjusted for relative
      humidity, temperature, visit number, and season, changes in three platelet
      function measures including (1) aggregation induced by adenosine diphosphate
      (ADP), (2) aggregation induced by collagen, and (3) thromboxane B2 production
      were associated with interquartile range (IQR) increases in mean concentrations
      of ambient PM2.5, black carbon, ultrafine particles (UFP; 10-100 nm), and
      accumulation mode particles (AMP; 100-500 nm) in the previous 1-96 h. IQR
      increases in mean UFP and AMP concentrations were associated with significant
      decreases in platelet response, with the largest being a -0.43 log(pg/ml)
      decrease in log(thromboxane B2) (95% CI = -0.8, -0.1) associated with each 582
      particles/cm(3) increase in AMP, and a -1.7 ohm reduction in collagen-induced
      aggregation (95% CI = -3.1, -0.3) associated with each 2097-particles/cm(3)
      increase in UFP in the previous 72 h. This UFP effect on thromboxane B2 was
      significantly muted in diabetic subjects taking aspirin (-0.01 log[pg/ml]; 95% CI
      = -0.4, 0.3). The reason for this finding remains unknown, and needs to be
      investigated in future studies. 

PMID- 27029329
TI  - [Results of surgical treatment of syringomyelia associated with Chiari 1
      malformation. An analysis of 125 cases].
AB  - The rate of Chiari malformation (CM) in a population ranges from 3 to 8 per
      100,000 population. In 62-80% of cases, CM is accompanied by the development of
      syringomyelia (SM) at various levels. The clinical picture in these patients is a
      combination of CM and SM manifestations; however, SM symptoms often prevail,
      which creates some problems in the diagnosis of the disease and in the choice of
      optimal treatment. OBJECTIVE: On the basis of our own experience of surgical
      interventions, we aimed to clarify the indications for surgical treatment of SM
      associated with CM and to determine the optimal amount of surgery and the
      criteria for evaluation of treatment outcomes. MATERIAL AND METHODS: Two hundred
      twenty five patients with a combination of syringomyelia and Chiari 1
      malformation were examined in the period from 2011 to February 2015. Of them, 125
      patients were operated on. The mean age of the operated patients was 56+/-8
      years. The mean time from the appearance of the first signs of the disease to
      surgery was 75+/-82 months. All operations were performed by a single surgeon.
      The operations were carried out in the half-sitting (89.6%) or prone (10.4%)
      position. The operation included sparing suboccipital craniectomy, C1 arch
      resection, recovery of the cerebrospinal fluid (CSF) circulation along the
      posterior surface of the cerebellum, and reconstruction of the dura mater in the
      craniovertebral junction region. RESULTS: Exploration of the arachnoid mater of
      the cisterna magna after dura opening revealed no arachnopathy in 78 (62.4%)
      patients (Chiari 0 malformation according to Klekamp). The type 1 arachnopathy
      (by Klekamp) was detected in 31 patients (24.8%), and the type 2 arachnopathy was
      observed in 16 (12.8%). The condition of 109 (88%) patients was evaluated one
      year after the surgery. Sixty one (56%) patients had partial or complete
      regression of preoperative neurological symptoms. The disease stopped progressing
      in 44 patients (40%). The disease was progressing in 4 (3.7%) patients. No
      recurrence of a CSF circulation disturbance at the craniovertebral level was
      observed during follow-up. Early postoperative complications occurred in 4 (3.2%)
      patients: wound CSF leakage in 1 (0.8%) patient, acute epidural hematoma in 1
      (0.8%) patient, and aseptic meningitis in 2 (1.6%) patients. Temporary
      deteriorations in the condition (headache worsening, meteosensitivity) were
      detected in 11 (8.9%) patients. These symptoms regressed by the end of the 1st
      postoperative month. There were no deaths. CONCLUSIONS: The indication for
      surgery in patients with a combination of CM and SM is the presence of
      neurological symptoms associated with syringomyelia and their progression as well
      as headache caused by herniation of the cerebellar tonsils, which significantly
      deteriorates the patient's quality of life. The main criteria for evaluating the
      efficacy of treatment include stabilization of the clinical symptoms and/or
      improvement in the patient condition. Suboccipital craniectomy followed by
      reconstruction of the dura mater and recovery of the CSF circulation in the
      craniovertebral region is an effective treatment of syringomyelia associated with
      Chiari 1 malformation.

PMID- 27029330
TI  - [Amygdalohippocampectomy in treatment of epilepsy in patients with temporal lobe
      cavernomas].
AB  - BACKGROUND: In some cases, single-stage or delayed amygdalohippocampectomy (AHE)
      can be used for effective treatment of epileptic syndrome upon resection of
      temporal lobe cavernomas. The efficacy of AHE in treatment of temporal epilepsies
      is proved in general; however, the indications for surgery in patients with
      cavernomas are not developed. OBJECTIVE: The study objective was to evaluate the
      efficacy and safety AHE in the treatment of epilepsy in patients with temporal
      lobe cavernomas and to define the indications for surgery. MATERIAL AND METHODS:
      Of 14 patients with temporal lobe cavernomas, which manifested as epileptic
      seizures, 10 patients underwent selective AHE, and 4 patients underwent
      anteromedial temporal lobectomy. In 12 cases, AHE was performed simultaneously
      with cavernoma resection. Delayed AHE was carried out in 2 cases. All patients
      underwent preoperative MRI and EEG. Preoperative video-EEG monitoring was
      performed in 3 cases. The duration of postoperative follow-up was at least 1 year
      (mean follow-up was 3.3 years). RESULTS: Improvement in the epileptic syndrome
      was observed in all patients. In the postoperative period, 7 patients had no
      seizures (Engel class IA); of them, 3 patients discontinued anticonvulsants. The
      surgery outcome depended on the disease duration. Significant postoperative
      complications in the form of reversible hemiparesis were observed in 1 case.
      CONCLUSION: Amygdalohippocampectomy is highly efficient in treatment of severe
      forms of epilepsy in patients with temporal lobe cavernomas. In the case of long
      history of typical temporal seizures and pharmacoresistant epilepsy, AHE can be
      performed simultaneously with cavernoma resection.

PMID- 27029331
TI  - [Trigeminal neuralgia and hemifacial spasm associated with vertebrobasilar artery
      tortuosity].
AB  - BACKGROUND: The tortuous vertebrobasilar artery (TVBA) often causes neurovascular
      conflicts in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS).
      Implementation of microvascular decompression (MVD) in these circumstances is
      hindered due to stiffness of the enlarged and dilated arteries and is often
      accompanied by poor outcomes. The surgical strategy in cases of trigeminal
      neuralgia and hemifacial spasm associated with the TVBA should be clarified in
      order to achieve good outcomes. MATERIAL AND METHODS: MVD was performed in 268 TN
      patients and 71 HFS patients. The TVBA as a compressing vessel was identified in
      30 cases (11 cases of TN, 18 cases of HFS, and 1 patient with painful tic
      convulsif). All patients underwent MVD and a retrospective analysis of clinical
      outcomes. RESULTS: Compression caused by the vertebral artery was found in all
      HFS patients and 4 TN patients, and compression caused by the basilar artery was
      observed in 7 TN cases. Additional compression of the cranial nerve root
      entry/exit zone by cerebellar vessels was observed in 21 cases. The TVBA was
      mobilized by dissection of arachnoid adhesions between the vessel and the
      brainstem and retracted laterally. Then, the TVBA was retracted from the
      brainstem to the caudorostral direction. These manipulations resulted is
      "spontaneous" decompression of the cranial nerves without placing prostheses
      between the artery and the nerve root entry/exit zone. In all cases (except two),
      the displaced TVBA was fixed between the enlarged artery and brainstem using
      pieces of the patient's muscle and adipose tissues, followed by application of
      fibrin glue. A cylindrical silicone prosthesis was used in 1 case. In another
      case, the TVBA was retracted using a fascial loop fixed to the dura mater of the
      petrous pyramid by means of a suture. After application of MVD, TN and HFS
      symptoms completely regressed. There were several transient complications and 2
      cases of permanent hearing loss. No clinical symptom recurrence was observed.
      CONCLUSION: MVD is the most effective surgical treatment of TN and HFS caused by
      the TVBA. The TVBA should be retracted from the brainstem without placing
      prostheses in the nerve root entry/exit zone.

PMID- 27029332
TI  - [The rate of hyponatremia in neurosurgical patients (comparison between the data
      from the Burdenko Neurosurgical Instutite and the literature) and recommendations
      for the diagnosis and treatment].
AB  - Hyponatremia is a relatively frequent and serious complication in patients with
      various neurosurgical pathologies. OBJECTIVE: This study is aimed at assessing
      the incidence of hyponatremia in neurosurgical patients depending on the
      pathology. MATERIAL AND METHODS: This paper presents a retrospective analysis 39
      479 cases of patients operated on at the Burdenko Neurosurgical Institute from
      2008 to 2014. RESULTS: A total of 785 hyponatremic patients with Na level lower
      than 130 mmol/l (2% of all operated patients) were identified. Mortality in
      patients with hyponatremia was 14.3%, which is tenfold higher compared to the
      rest of population of patients without hyponatremia who were operated on during
      the same period. In adults, hyponatremia most frequently occurred after resection
      of craniopharyngiomas (11%) and as a result of acute cerebrovascular accident
      (22%). In children, it occurred after resection of craniopharyngiomas (10%),
      astrocytomas (7%), ependymomas (24%), and germ cell tumors (10.5%). CONCLUSION:
      This study, which was mainly statistical one, was not aimed at detailed
      investigation of hyponatremia in different groups of neurosurgical patients. We
      only tried to draw the attention of various experts to those categories of
      patients, where focused and in-depth developments are more than important.
      Obviously, already gained international experience should be taken into account
      for this PURPOSE: Therefore, this article presents the literature data on the
      etiology and pathogenesis of hyponatremia. We describe the details of the various
      classifications of hyponatremia, its clinical symptoms, diagnosis, and
      treatments, primarily based on the recommendations of the last European consensus
      of various specialists (2014).

PMID- 27029333
TI  - [Basal ganglia germinomas in children. Four clinical cases and a literature
      review].
AB  - Basal ganglia germinomas are a specific group of intracranial germinomas. Their
      early diagnosis is complicated due to their atypical localization and diversity
      of neuroimaging and clinical signs. MATERIAL AND METHODS: We describe 4 cases of
      basal ganglia germinoma in boys of 13, 14, 15, and 16 years of age. The medical
      history data, clinical features, neuroimaging and histological characteristics of
      basal ganglia germonomas, and preliminary results of the treatment are presented.
      CONCLUSION: Basal ganglia germinomas are usually verified at the late stage of
      the disease when patients are detected with extended lesions of the basal ganglia
      and severe neurological and neuroendocrine deficits. This situation is due to
      clinical and imaging signs that are untypical of common germinomas.

PMID- 27029334
TI  - [A clinical case of combined treatment of a patient with breast cancer and
      metastases to the brain and meninges].
AB  - The article describes a clinical case of successful chemotherapeutic and
      radiation treatment of a patient with breast cancer and metastases to the brain
      and meninges and with a pronounced neurological deficit. The patient underwent
      combined treatment (whole brain radiation with TBD of 30 Gy and local radiation
      of a metastasis with TBD of 15 Gy associated with capecitabine therapy) with
      continued administration of capecitabine until improvement. A partial metastasis
      reduction by 50% and complete regression of the neurological deficit were
      observed. Disease-free period was 1 year and 10 months, and the overall survival
      amounted to 2 years.

PMID- 27029335
TI  - [Surgical treatment of clival and axis bone cysts].
AB  - OBJECTIVE: The study objective is to present the tactics of surgical treatment of
      simple (solitary) bone cysts of the clival region and CII body. MATERIAL AND
      METHODS: Two patients were operated on for simple clival and axis cysts. RESULTS:
      The first patient with a simple clival cyst underwent transoral clivectomy and
      bone cyst evacuation. Postoperative control SCT scans revealed that the cyst
      cavity was lined with a hemostatic material and biological glue. Restoration of
      bone structures of the clivus occurred after 8 months. The second patient with a
      simple cyst of the second cervical vertebra (axis) underwent a two-stage surgical
      treatment: occipitospondylodesis was carried out first, and transoral removal of
      the pathological process of the CII body was performed at the second stage.
      Control scans a year after the surgery revealed the formation of bone tissue in
      the axis body region, an increased cystic cavity in the odontoid process of the
      axis, and posterior migration of the odontoid process, which caused compression
      of the brainstem structures. In connection with this, we performed transoral re
      intervention with removal of the cystic separated odontoid process. Postoperative
      control scans revealed complete removal of the cystic odontoid process and
      decompression of the dural sac. The article provides a detailed analysis of the
      modern literature that has not reported any cases of a simple bone cyst located
      in the clivus or upper cervical vertebrae region and, thus, has not described the
      tactics for surgical treatment of these complex diseases. The article presents
      illustrative pre-, intra-, and postoperative images and histological specimens.
      CONCLUSION: The described cases present successful recurrence-free surgical
      treatment of simple (solitary) bone cysts located both in the clivus region (1
      case) and in the body and odontoid process of the axis (1 case). A feature of the
      second case was that the patient had an extremely rare combination of a bone cyst
      of the C2 body and the cystic separated odontoid process of the axis (cystic os
      odontoideum).

PMID- 27029336
TI  - [Guidelines for the diagnosis and treatment of severe traumatic brain injury.
      Part 2. Intensive care and neuromonitoring].
AB  - Traumatic brain injury (TBI) is one of the major causes of death and disability
      in young and middle-aged people. The most problematic group is comprised of
      patients with severe TBI who are in a coma. The adequate diagnosis of primary
      brain injuries and timely prevention and treatment of the secondary injury
      mechanisms largely define the possibility of reducing mortality and severe
      disabling consequences. When developing these guidelines, we used our experience
      in the development of international and national recommendations for the
      diagnosis and treatment of mild traumatic brain injury, penetrating gunshot
      wounds to the skull and brain, severe traumatic brain injury, and severe
      consequences of brain injuries, including a vegetative state. In addition, we
      used international and national guidelines for the diagnosis, intensive care, and
      surgical treatment of severe traumatic brain injury, which had been published in
      recent years. The proposed guidelines concern intensive care of severe TBI in
      adults and are particularly intended for neurosurgeons, neurologists,
      neuroradiologists, anesthesiologists, and intensivists who are routinely involved
      in the treatment of these patients.

PMID- 27029338
TI  - Scaling Laws for Thin Films near the Superconducting-to-Insulating Transition.
AB  - We propose a Lagrangian function, which combines Landau-Ginzburg term and Chern
      Simons term, for describing the competition between disorder and
      superconductivity. To describe the normal-to-superconducting transition in the
      thin superconducting films, we apply Wilson's renormalization group methods into
      this Lagrangian function. Finally, we obtain a scaling law between critical
      temperature (Tc), film thickness (d), sheet resistance of the film at the normal
      state (Rs), and number density of the electrons at the normal state (N). Such a
      scaling law is in agreement with recent experimental investigations [Ivry, Y. et
      al., Physical Review B 90, 214515 (2014)]. Our finding may have potential
      benefits for improving transition temperature Tc. 

PMID- 27029337
TI  - Inversions and adaptation to the plant toxin ouabain shape DNA sequence variation
      within and between chromosomal inversions of Drosophila subobscura.
AB  - Adaptation is defined as an evolutionary process allowing organisms to succeed in
      certain habitats or conditions. Chromosomal inversions have the potential to be
      key in the adaptation processes, since they can contribute to the maintenance of
      favoured combinations of adaptive alleles through reduced recombination between
      individuals carrying different inversions. We have analysed six genes (Pif1A,
      Abi, Sqd, Yrt, Atpalpha and Fmr1), located inside and outside three inversions of
      the O chromosome in European populations of Drosophila subobscura. Genetic
      differentiation was significant between inversions despite extensive
      recombination inside inverted regions, irrespective of gene distance to the
      inversion breakpoints. Surprisingly, the highest level of genetic differentiation
      between arrangements was found for the Atpalpha gene, which is located outside
      the O1 and O7 inversions. Two derived unrelated arrangements (O3+4+1 and O3+4+7)
      are nearly fixed for several amino acid substitutions at the Atpalpha gene that
      have been described to confer resistance in other species to the cardenolide
      ouabain, a plant toxin capable of blocking ATPases. Similarities in the Atpalpha
      variants, conferring ouabain resistance in both arrangements, may be the result
      of convergent substitution and be favoured in response to selective pressures
      presumably related to the presence of plants containing ouabain in the geographic
      locations where both inversions are present. 

PMID- 27029339
TI  - Abatacept monotherapy compared with abatacept plus disease-modifying anti
      rheumatic drugs in rheumatoid arthritis patients: data from the ORA registry.
AB  - BACKGROUND: Retention rate, efficacy, and safety of abatacept (ABA) was compared
      between patients with rheumatoid arthritis receiving ABA as monotherapy to those
      in combination ABA + conventional synthetic DMARD (csDMARD). METHODS: The
      patients were obtained from the ORA registry. The retention rate was analysed in
      two ways: (1) therapeutic strategy retention, in which the addition of a csDMARD
      was considered to indicate failure of the monotherapy strategy; and (2) ABA
      retention, which was assessed by the discontinuation of ABA regardless of other
      treatment modifications. Efficacy and safety were compared between ABA initiated
      alone and ABA used in combination with a csDMARD. RESULTS: The retention rate at
      month 6 (M6) was evaluated in 569 patients. A significant difference was
      identified in the retention rate between the ABA monotherapy strategy and the ABA
      + csDMARD strategy (58.5 % [110/188] vs. 68 % [258/381], respectively, p =
      0.031). No significant difference was identified in the ABA retention rate
      initiated either as a monotherapy or in combination with csDMARDs (75 % [142/188]
      vs. 76 % [291/381], respectively, p = 0.824). Data regarding ABA efficacy were
      available for 444 patients. There was no significant difference in the responder
      proportion after 6 months of treatment between ABA monotherapy and ABA + csDMARD
      treatment (60.2 % [88/146] vs. 60 % [179/298], respectively, p = 0.967).
      CONCLUSIONS: This "real-life" analysis, which is relevant for bedside practice,
      emphasised the satisfactory efficacy and safety of ABA used in monotherapy, which
      provides an acceptable alternative when csDMARDs are undesirable.

PMID- 27029340
TI  - Comparison of the effectiveness of polyethylene glycol with and without
      electrolytes in constipation: a systematic review and network meta-analysis.
AB  - BACKGROUND: Polyethylene glycol is commonly used to manage constipation and is
      available with or without electrolytes. The addition of electrolytes dates back
      to its initial development as lavage solutions in preparation for
      gastrointestinal interventions. The clinical utility of the addition of
      electrolytes to polyethylene glycol for the management of constipation is not
      established. The objective of this systematic review and network meta-analysis
      (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG +
      E) or without electrolytes (PEG) in the management of functional constipation in
      adults. METHODS: A systematic review was conducted to identify randomised
      controlled clinical trials that assessed the use of polyethylene glycol in
      functional constipation. The primary outcome was the mean number of bowel
      movements per week. RESULTS: Nineteen studies were included in the NMA (PEG N =
      9, PEG + E N = 8, PEG versus PEG + E N = 2; involving 2247 patients). PEG and PEG
      + E are both effective, increasing the number of bowel movements per week by 1.8
      (95 % Crl 1.0, 2.8) and 1.9 (95 % Crl 0.9, 3.0) respectively versus placebo and
      by 1.8 (95 % Crl 0.0, 3.5) and 1.9 (95 % Crl 0.2, 3.6) respectively versus
      lactulose. There was no efficacy difference between PEG + E and PEG (0.1, 95 %
      Crl -1.1, 1.2) and there were no differences in safety or tolerability.
      CONCLUSIONS: Polyethylene glycol with and without electrolytes are effective and
      safe treatments for constipation in adults. The addition of electrolytes to
      polyethylene glycol does not appear to offer any clinical benefits over
      polyethylene glycol alone in the management of constipation.

PMID- 27029341
TI  - Stereotactic body radiotherapy for spine and bony pelvis using flattening filter
      free volumetric modulated arc therapy, 6D cone-beam CT and simple positioning
      techniques: Treatment time and patient stability.

PMID- 27029342
TI  - Effects of pregabalin on the nociceptive, emotional and cognitive manifestations
      of neuropathic pain in mice.
AB  - BACKGROUND: Preclinical drug discovery for the treatment of chronic pain is at
      present challenged by the difficulty to study behaviours comparable to the
      complex human pain experience in animals. Several reports have demonstrated a
      frequent association of chronic pain in humans with affective disorders, such as
      anxiety and depression, and impaired cognitive functions, including memory and
      decision making, and motivation for goal-directed behaviours. In this study, we
      validated different behavioural outcomes to measure the emotional and cognitive
      manifestations of neuropathic pain induced in mice by partial sciatic nerve
      ligation. METHODS: In these mice, we evaluated at different time points the
      nociceptive responses, the anxiety- and depressive-like behaviours, the anhedonic
      state, object recognition memory and the operant responding maintained by food
      and the effects of the repeated administration of pregabalin on these
      manifestations. RESULTS: Our results demonstrated that the presence of allodynia
      and hyperalgesia in neuropathic pain mice was associated with increased anxiety-
      and depressive-like behaviours, reduced memory functions, development of an
      anhedonic state and impaired motivation to obtain food in the operant task.
      Chronic pregabalin treatment improved the nociceptive, anxiety-like and anhedonic
      responses, as well as the memory deficit, but did not modify the depressive-like
      alterations and the decreased motivation in these mice. CONCLUSIONS: These
      results indicate that some emotional manifestations of chronic pain do not
      necessarily resolve when pain is relieved and underline the relevance to evaluate
      multiple behavioural responses associated with chronic pain, including the
      affective-motivational and cognitive behaviours, to increase the predictive value
      of preclinical drug discovery. WHAT DOES THIS STUDY ADD?: In this study, we have
      validated different behavioural outcomes allowing a reliable measurement of the
      emotional and cognitive manifestations of neuropathic pain induced in mice by
      partial sciatic nerve ligation. These results underline the relevance to evaluate
      these multiple pain-related alterations to improve the predictive value of
      preclinical drug discovery.

PMID- 27029343
TI  - The microenvironment controls invadosome plasticity.
AB  - Invadosomes are actin-based structures involved in extracellular matrix
      degradation. Invadosomes is a term that includes podosomes and invadopodia, which
      decorate normal and tumour cells, respectively. They are mainly organised into
      dots or rosettes, and podosomes and invadopodia are often compared and
      contrasted. Various internal or external stimuli have been shown to induce their
      formation and/or activity. In this Commentary, we address the impact of the
      microenvironment and the role of matrix receptors on the formation, and dynamic
      and degradative activities of invadosomes. In particular, we highlight recent
      findings regarding the role of type I collagen fibrils in inducing the formation
      of a new linear organisation of invadosomes. We will also discuss invadosome
      plasticity more generally and emphasise its physio-pathological relevance.

PMID- 27029344
TI  - Getting membrane proteins on and off the shuttle bus between the endoplasmic
      reticulum and the Golgi complex.
AB  - Secretory proteins exit the endoplasmic reticulum (ER) in coat protein complex II
      (COPII)-coated vesicles and then progress through the Golgi complex before
      delivery to their final destination. Soluble cargo can be recruited to ER exit
      sites by signal-mediated processes (cargo capture) or by bulk flow. For membrane
      proteins, a third mechanism, based on the interaction of their transmembrane
      domain (TMD) with lipid microdomains, must also be considered. In this
      Commentary, I review evidence in favor of the idea that partitioning of TMDs into
      bilayer domains that are endowed with distinct physico-chemical properties plays
      a pivotal role in the transport of membrane proteins within the early secretory
      pathway. The combination of such self-organizational phenomena with canonical
      intermolecular interactions is most likely to control the release of membrane
      proteins from the ER into the secretory pathway. 

PMID- 27029345
TI  - Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma
      Multiforme.
AB  - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has tremendous
      promise in treating various forms of cancers. However, many cancer cells exhibit
      or develop resistance to TRAIL. Interestingly, many studies have identified
      several secondary agents that can overcome TRAIL resistance. To expand on these
      studies, we conducted an extensive drug-re-profiling screen to identify FDA
      approved compounds that can be used clinically as TRAIL-sensitizing agents in a
      very malignant type of brain cancer, Glioblastoma Multiforme (GBM). Using
      selected isogenic GBM cell pairs with differential levels of TRAIL sensitivity,
      we revealed 26 TRAIL-sensitizing compounds, 13 of which were effective as single
      agents. Cardiac glycosides constituted a large group of TRAIL-sensitizing
      compounds, and they were also effective on GBM cells as single agents. We then
      explored a second class of TRAIL-sensitizing drugs, which were enhancers of TRAIL
      response without any effect on their own. One such drug, Mitoxantrone, a DNA
      damaging agent, did not cause toxicity to non-malignant cells at the doses that
      synergized with TRAIL on tumor cells. We investigated the downstream changes in
      apoptosis pathway components upon Mitoxantrone treatment, and observed that Death
      Receptors (DR4 and DR5) expression was upregulated, and pro-apoptotic and anti
      apoptotic gene expression patterns were altered in favor of apoptosis. Together,
      our results suggest that combination of Mitoxantrone and TRAIL can be a promising
      therapeutic approach for GBM patients.

PMID- 27029346
TI  - Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation
      of JH2 alphaC helix.
AB  - The mechanisms by which JAK2 is activated by the prevalent pseudokinase (JH2)
      V617F mutation in blood cancers remain elusive. Via structure-guided mutagenesis
      and transcriptional and functional assays, we identify a community of residues
      from the JH2 helix alphaC, SH2-JH2 linker and JH1 kinase domain that mediate
      V617F-induced activation. This circuit is broken by altering the charge of
      residues along the solvent-exposed face of the JH2 alphaC, which is predicted to
      interact with the SH2-JH2 linker and JH1. Mutations that remove negative charges
      or add positive charges, such as E596A/R, do not alter the JH2 V617F fold, as
      shown by the crystal structure of JH2 V617F E596A. Instead, they prevent kinase
      domain activation via modulation of the C-terminal residues of the SH2-JH2
      linker. These results suggest strategies for selective V617F JAK2 inhibition,
      with preservation of wild-type function.

PMID- 27029348
TI  - Neuropsychological Criteria for Mild Cognitive Impairment and Dementia Risk in
      the Framingham Heart Study.
AB  - OBJECTIVES: To refine mild cognitive impairment (MCI) diagnostic criteria, we
      examined progression to dementia using two approaches to identifying MCI.
      METHODS: A total of 1203 Framingham Heart Study participants were classified at
      baseline as cognitively normal or MCI (overall and four MCI subtypes) via
      conventional Petersen/Winblad criteria (single cognitive test impaired per
      domain, >1.5 SD below expectations) or Jak/Bondi criteria (two tests impaired per
      domain, >1 SD below norms). Cox proportional hazards models were constructed to
      examine the association between each MCI definition and incident dementia.
      RESULTS: The Petersen/Winblad criteria classified 34% of participants as having
      MCI while the Jak/Bondi criteria classified 24% as MCI. Over a mean follow-up of
      9.7 years, 58 participants (5%) developed incident dementia. Both MCI criteria
      were associated with incident dementia [Petersen/Winblad: hazards ratio (HR) =
      2.64; p-value=.0002; Jak/Bondi: HR=3.30; p-value <.0001]. When both MCI
      definitions were included in the same model, only the Jak/Bondi definition
      remained statistically significantly associated with incident dementia (HR=2.47;
      p-value=.008). Multi-domain amnestic and single domain non-amnestic MCI subtypes
      were significantly associated with incident dementia for both diagnostic
      approaches (all p-values <.01). CONCLUSIONS: The Jak/Bondi MCI criteria had a
      similar association with dementia as the conventional Petersen/Winblad MCI
      criteria, despite classifying ~30% fewer participants as having MCI. Further
      exploration of alternative methods to conventional MCI diagnostic criteria is
      warranted. (JINS, 2016, 22, 937-943).

PMID- 27029347
TI  - High-affinity Anticalins with aggregation-blocking activity directed against the
      Alzheimer beta-amyloid peptide.
AB  - Amyloid beta (Abeta) peptides, in particular Abeta42 and Abeta40, exert
      neurotoxic effects and their overproduction leads to amyloid deposits in the
      brain, thus constituting an important biomolecular target for treatments of
      Alzheimer's disease (AD). We describe the engineering of cognate Anticalins as a
      novel type of neutralizing protein reagent based on the human lipocalin scaffold.
      Phage display selection from a genetic random library comprising variants of the
      human lipocalin 2 (Lcn2) with mutations targeted at 20 exposed amino acid
      positions in the four loops that form the natural binding site was performed
      using both recombinant and synthetic target peptides and resulted in three
      different Anticalins. Biochemical characterization of the purified proteins
      produced by periplasmic secretion in Escherichia coli revealed high folding
      stability in a monomeric state, with Tm values ranging from 53.4 degrees C to
      74.5 degrees C, as well as high affinities for Abeta40, between 95 pM and 563 pM,
      as measured by real-time surface plasmon resonance analysis. The central linear
      VFFAED epitope within the Abeta sequence was mapped using a synthetic peptide
      array on membranes and was shared by all three Anticalins, despite up to 13
      mutual amino acid differences in their binding sites. All Anticalins had the
      ability-with varying extent-to inhibit Abeta aggregation in vitro according to
      the thioflavin-T fluorescence assay and, furthermore, they abolished Abeta42
      mediated toxicity in neuronal cell culture. Thus, these Anticalins provide not
      only useful protein reagents to study the molecular pathology of AD but they also
      show potential as alternative drug candidates compared with antibodies.

PMID- 27029349
TI  - Atrial Fibrillation in Heart Failure: Should Catheter Ablation Play a Larger
      Role?

PMID- 27029350
TI  - Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in
      Patients With Congestive Heart Failure and an Implanted Device: Results From the
      AATAC Multicenter Randomized Trial.
AB  - BACKGROUND: Whether catheter ablation (CA) is superior to amiodarone (AMIO) for
      the treatment of persistent atrial fibrillation (AF) in patients with heart
      failure is unknown. METHODS AND RESULTS: This was an open-label, randomized,
      parallel-group, multicenter study. Patients with persistent AF, dual-chamber
      implantable cardioverter defibrillator or cardiac resynchronization therapy
      defibrillator, New York Heart Association II to III, and left ventricular
      ejection fraction <40% within the past 6 months were randomly assigned (1:1
      ratio) to undergo CA for AF (group 1, n=102) or receive AMIO (group 2, n=101).
      Recurrence of AF was the primary end point. All-cause mortality and unplanned
      hospitalization were the secondary end points. Patients were followed up for a
      minimum of 24 months. At the end of follow-up, 71 (70%; 95% confidence interval,
      60%-78%) patients in group 1 were recurrence free after an average of 1.4+/-0.6
      procedures in comparison with 34 (34%; 95% confidence interval, 25%-44%) in group
      2 (log-rank P<0.001). The success rate of CA in the different centers after a
      single procedure ranged from 29% to 61%. After adjusting for covariates in the
      multivariable model, AMIO therapy was found to be significantly more likely to
      fail (hazard ratio, 2.5; 95% confidence interval, 1.5-4.3; P<0.001) than CA. Over
      the 2-year follow-up, the unplanned hospitalization rate was (32 [31%] in group 1
      and 58 [57%] in group 2; P<0.001), showing 45% relative risk reduction (relative
      risk, 0.55; 95% confidence interval, 0.39-0.76). A significantly lower mortality
      was observed in CA (8 [8%] versus AMIO (18 [18%]; P=0.037). CONCLUSIONS: This
      multicenter randomized study shows that CA of AF is superior to AMIO in achieving
      freedom from AF at long-term follow-up and reducing unplanned hospitalization and
      mortality in patients with heart failure and persistent AF. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729911.

PMID- 27029351
TI  - Antidiabetic activity of the ethyl acetate fraction of Ficus lutea (Moraceae)
      leaf extract: comparison of an in vitro assay with an in vivo obese mouse model.
AB  - BACKGROUND: Ficus lutea crude acetone leaf extracts were previously shown to
      stimulate glucose uptake and insulin secretion of established cells and, inhibit
      alpha-amylase and alpha-glucosidase activities. METHODS: For this study, F. lutea
      acetone extracts were subjected to solvent-solvent fractionation to yield
      fractions with differing polarities (hexane, chloroform, dichloromethane, ethyl
      acetate, n-butanol and water) in an attempt to obtain a more potent fraction with
      in vitro and probably in vivo activity. RESULTS: Among these fractions, the ethyl
      acetate fraction had the highest total polyphenol content (100.5 +/- 1.6 mg GAE/g
      dried extract) and alpha-glucosidase inhibitory activity (126.8 +/- 30.6 MUg/ml).
      It also stimulated the highest glucose uptake of C2C12 muscle cells and decreased
      extracellular glucose concentration of H-4-II-E liver cells with low cytotoxic
      activity. The ethyl acetate fraction (10.88 +/- 0.55 MUg/L at 250 MUg/ml)
      enhanced insulin secretion in RIN-m5F pancreatic beta-cells to the same degree as
      the positive control glibenclamide (11.09 +/- 0.07 MUg/L at 1MUM). While
      fractionation increased alpha-glucosidase inhibition and glucose uptake of cells,
      in the ethyl acetate fraction, the alpha-amylase inhibition and insulin secretion
      decreased. The weight reducing and glucose control potential of the ethyl acetate
      fraction in an obese mouse model, important factors in the amelioration of type
      II diabetes was determined. The extract had no statistical significant weight
      reducing activity. CONCLUSION: A major finding was the decrease in the area under
      the curve of the glucose concentration over time in animals that were treated
      with both a change in diet and with the plant extract. This is linked to
      increased glucose uptake within the cells, the most likely mechanism is either an
      increased insulin response or increased insulin secretion.

PMID- 27029352
TI  - On the metabolic interactions of (photo)respiration.
AB  - Given that photorespiration is inextricably linked to the process of
      photosynthesis by virtue of sharing the common first enzyme Rubisco, the
      photorespiratory pathway has been less subject to study in isolation than many
      other metabolic pathways. That said, despite often being described to be linked
      to reactions of ammonia assimilation, C1 metabolism and respiratory metabolism,
      the precise molecular mechanisms governing these linkages in land plants remain
      partially obscure. The application of broad metabolite profiling on mutants with
      altered levels of metabolic enzymes has facilitated the identification of common
      and distinct metabolic responses among them. Here we provide an update of the
      recent findings from such studies, focusing particularly on the interplay between
      photorespiration and the metabolic reactions of mitochondrial respiration. In
      order to do so we evaluated (i) changes in organic acids following environmental
      perturbation of metabolism, (ii) changes in organic acid levels in a wide range
      of photorespiratory mutants, (iii) changes in levels of photorespiratory
      metabolites in transgenic tomato lines deficient in the expression of enzymes of
      the tricarboxylic acid cycle. In addition, we estimated the rates of
      photorespiration in a complete set of tricarboxylic acid cycle transgenic tomato
      lines. Finally, we discuss insight concerning the interaction between
      photorespiration and other pathways that has been attained following the
      development of (13)CO2-based flux profiling methods.

PMID- 27029353
TI  - The calmodulin-like proteins AtCML4 and AtCML5 are single-pass membrane proteins
      targeted to the endomembrane system by an N-terminal signal anchor sequence.
AB  - Calmodulins (CaMs) are important mediators of Ca(2+) signals that are found
      ubiquitously in all eukaryotic organisms. Plants contain a unique family of
      calmodulin-like proteins (CMLs) that exhibit greater sequence variance compared
      to canonical CaMs. The Arabidopsis thaliana proteins AtCML4 and AtCML5 are
      members of CML subfamily VII and possess a CaM domain comprising the
      characteristic double pair of EF-hands, but they are distinguished from other
      members of this subfamily and from canonical CaMs by an N-terminal extension of
      their amino acid sequence. Transient expression of yellow fluorescent protein
      tagged AtCML4 and AtCML5 under a 35S-promoter in Nicotiana benthamiana leaf cells
      revealed a spherical fluorescence pattern. This pattern was confirmed by
      transient expression in Arabidopsis protoplasts under the native promoter. Co
      localization analyses with various endomembrane marker proteins suggest that
      AtCML4 and AtCML5 are localized to vesicular structures in the interphase between
      Golgi and the endosomal system. Further studies revealed AtCML5 to be a single
      pass membrane protein that is targeted into the endomembrane system by an N
      terminal signal anchor sequence. Self-assembly green fluorescent protein and
      protease protection assays support a topology with the CaM domain exposed to the
      cytosolic surface and not the lumen of the vesicles, indicating that AtCML5 could
      sense Ca(2+) signals in the cytosol. Phylogenetic analysis suggests that AtCML4
      and AtCML5 are closely related paralogues originating from a duplication event
      within the Brassicaceae family. CML4/5-like proteins seem to be universally
      present in eudicots but are absent in some monocots. Together these results show
      that CML4/5-like proteins represent a flowering plant-specific subfamily of CMLs
      with a potential function in vesicle transport within the plant endomembrane
      system.

PMID- 27029354
TI  - Quantitative phosphoproteomics of protein kinase SnRK1 regulated protein
      phosphorylation in Arabidopsis under submergence.
AB  - SNF1 RELATED PROTEIN KINASE 1 (SnRK1) is proposed to be a central integrator of
      the plant stress and energy starvation signalling pathways. We observed that the
      Arabidopsis SnRK1.1 dominant negative mutant (SnRK1.1 (K48M) ) had lower
      tolerance to submergence than the wild type, suggesting that SnRK1.1-dependent
      phosphorylation of target proteins is important in signalling pathways triggered
      by submergence. We conducted quantitative phosphoproteomics and found that the
      phosphorylation levels of 57 proteins increased and the levels of 27 proteins
      decreased in Col-0 within 0.5-3h of submergence. Among the 57 proteins with
      increased phosphorylation in Col-0, 38 did not show increased phosphorylation
      levels in SnRK1.1 (K48M) under submergence. These proteins are involved mainly in
      sugar and protein synthesis. In particular, the phosphorylation of MPK6, which is
      involved in regulating ROS responses under abiotic stresses, was disrupted in the
      SnRK1.1 (K48M) mutant. In addition, PTP1, a negative regulator of MPK6 activity
      that directly dephosphorylates MPK6, was also regulated by SnRK1.1. We also
      showed that energy conservation was disrupted in SnRK1.1 (K48M) , mpk6, and PTP1
      (S7AS8A) under submergence. These results reveal insights into the function of
      SnRK1 and the downstream signalling factors related to submergence.

PMID- 27029355
TI  - Possible way for reduction of reported catastrophic blindness due to injection of
      steroid in the treatment of keloid scar.

PMID- 27029356
TI  - [New challenges of malaria elimination in China].
AB  - National malaria elimination action was initiated in china, 2010. The strategy of
      malaria elimination focused on the investigation and disposal of malaria case and
      foci, and technical measure of '1-3-7' model was implemented to ensure effective
      case detection and validation, case category and treatment, and the foci
      identification and disposal. During the past several years, the geographic scope
      of malaria transmission was shrunk sharply, and a overwhelming majority of areas
      have successfully interrupted local transmission of malaria. However, to achieve
      the goal of national malaria elimination in 2020, several new challenges were
      faced, which included the following ones: local malaria sustained transmission in
      the cross-bordering and remote areas, increasing trend of overseas imported
      malaria, introduced malaria among domestic migrant population, and the
      elimination of species of P. vivax and P. oval. Therefore, in the specific areas
      and among the high-risk population, it's critical to take effective actions to
      ensure malaria case and transmission foci detection, identification,
      classification, and disposal in the following years. 

PMID- 27029358
TI  - [Comparison of demographical characteristics of malaria cases from malaria
      control to elimination in China].
AB  - OBJECTIVE: To further identify the high-risk population at malaria elimination
      phase, and to provide the scientific evident for targeted prevention and control
      measures, we compared the demographical feature and its change trend for malaria
      cases between malaria control stage and elimination stage in China. METHODS: The
      data of individual case (probable and confirmed) and population during 2007-2014
      were collected from China National Notifiable Infectious Disease Reporting
      Information System, and the data of epidemiological investigation for malaria
      case (imported and indigenous) during 2011-2014 were collected from China
      Parasite Disease Prevention and Control Information System. All of the data
      didn't include China's Hongkong, Macao, Taiwan and foreign cases. We described
      the demographic features of malaria cases, e.g. sex, age, occupation and
      mobility, to compare the differences of cases between malaria control stage (2007
      2010) and the elimination phase (2011-2014). RESULTS: From 2007 to 2014, a total
      of 108 076 malaria cases were reported nationwide, which 13 355 cases were
      reported at the elimination stage. The proportion of male cases considerably
      increased from 65.1% (6 1625 cases) at the control stage to 91.4% (12 209 cases)
      at the elimination phase, with the cases aged 15-64 years among male cases
      dramatically rose from 74.3% (45 793 cases) to 97.2% (11 870 cases). In terms of
      occupation, the proportion of children and students decreased from 17.8% (16 891
      cases) to 2.7% (356 cases), while the percentage of migrant workers, workers and
      other professional cases increased from 8.5% (8 031 cases), 3.5% (3 319 cases)
      and 3.6% (3 435 cases) to 13.1% (1 757 cases), 11.5% (1 534 cases) and 11.4% (1
      517 cases), respectively. During the elimination stage,P. faliparium cases have
      higher proportion of male (96.4%, 7 179 cases) and adult aged 15-64 year (99.4%,
      7 399 cases) than that of P. vivax cases , 83.9% (4 344 cases) and 90.3% (4 679
      cases), respectively. Moreover, the proportion of imported cases rose from 63.6%
      (2 599 cases) in 2011 to 97.7% (2 854 cases) in 2014, and the proportion of the
      migrants in indigenous cases also showed an increasing trend from 13.5% (201
      cases) in 2011 to 28.4% (19 cases) in 2014. CONCLUSION: Compared with the control
      stage, great changes of demographical characteristics of malaria cases occurred
      at the elimination stage. Male adults aged 15-64 year-old, imported cases and
      domestic migrants were the high-risk population for targeted control and
      prevention at the malaria elimination stage.

PMID- 27029357
TI  - [Adverse effects of low dose exposures to cadmium below renal damage level should
      be emphasized for human health effect studies].
AB  - Currently, the pollution of heavy metal, including lead, cadmium (Cd) and
      mercury, was one of the major environmental problems in China. Cd could cause
      adverse effects on kidney, bone, lung and reproductive system. Most of the past
      researches focused on renal damage effect, and some evidences suggestedadverse
      effects on bone, tumor, cardiovascular diseases, diabetes and mineral elements,
      etc, which was occurred at low dose exposures to Cd below renal damage level. An
      important content of human health effect Studies on exposures to Cd is to follow
      up the development and consequences of adverse effects after long-term exposure
      to environmental Cd and then reduction or cessation of its exposure among this
      population. In this paper, the progress and development trend of long-term
      environmental exposure to Cd and its health damage effect were reviewed. 

PMID- 27029359
TI  - [Epidemiological analysis of the deaths of malaria in China, 2005-2014].
AB  - OBJECTIVE: To explore the epidemiological features of deaths of malaria from 2005
      to 2014, so as to provide the evidence for subsequently more effective strategic
      planning of malaria elimination in China. METHODS: The data of individual malaria
      cases (including probable and confirmed cases, population data, geographic
      distribution, diagnosis and reporting information) were obtained from the
      National Notifiable Infectious Disease Reporting Information System from 2005 to
      2014 and the epidemiological investigation information (including the clinical
      systems and the imported and indigenous cases) was extracted from Parasite
      Disease Prevention and Control Information System from 2011 to 2014. All of the
      data didn't include Hongkong, Macao, Taiwan and foreign cases. The population
      characteristics, clinical systems, geographic distribution, diagnosis and
      reporting and sources of infections of deaths were analyzed. RESULTS: From 2005
      to 2014, a total of 228 deaths of malaria were reported, with 203 (89.0%) of P.
      falciparum malaria, 13 (5.7%) of P. vivax malaria, 1 (0.5%) of P. malariae
      malaria and 11(4.8%) other cases. The fatality rate of malaria increased since
      2010. Among the deaths, 48 (81.4% ) had serious complications, which included
      cerebral lesion, coma, severe renal and hepatic injuries and hemolysis and so on.
      In 2005-2010, the geographical distribution of malaria deaths was mainly in
      Yunnan (78 deaths, 56.1%), Sichuan (13 deaths, 9.4%), Henan (7 deaths, 5.0%),
      Shandong (6 deaths, 4.3%) and Zhejiang (5 deaths, 3.6%) province. However, since
      the initiation of malaria elimination program in 2010, the areas with malaria
      deaths have changed, which mainly distributed in Henan (10 deaths, 11.2%),
      Sichuan (9 deaths, 10.1%), Shandong (8 deaths, 9.0%), Jiangsu (7 deaths, 7.9%)
      and Hunan province (7 deaths, 7.9%). Besides there were nine deaths (10.0%)
      reported in non-endemic areas of malaria (Beijing, Inner Mongolia, Jilin, and
      Ningxia) in 2011-2014. The median time from illness onset to diagnosis for deaths
      was 5.5 (P25-P75: 3.0-8.5) d, which was longer than 3.0 (2.0-6.0)d for survivors.
      Moreover, for deaths, the median P50 (P25-P75)(6.0, 4.0-9.0 d) from illness onset
      to diagnosis in 2011-2014 was longer than that in 2005-2010 (5.0, 3.0-9.0 d).
      Among imported deaths, 77 deaths (90.6%) originated from Africa and 8 deaths
      (9.4%) from Southeast Asia. CONCLUSION: Although the reported deaths of malaria
      were stable in 2005-2014, the geographical distribution of malaria deaths changed
      significantly and the time from illness onset to the diagnosis was longer since
      2010. Special attention should be paid to the diagnosis and treatment of imported
      cases to reduce the fatality at the malaria elimination stage.

PMID- 27029360
TI  - [Epidemic features and impact factors on hospitalization of Plasmodium vivax in
      China 2011-2014].
AB  - OBJECTIVE: To investigate the epidemiological characteristics and impact factors
      on hospitalization of Plasmodium vivax (P.vivax) since initiation of national
      malaria elimination program, so as to facilitate the adjustment of technical
      guideline in response to the epidemic changing of malaria in China. METHODS: The
      data of individual P. vivax case (probable and confirmed) and population during
      2011-2014 were collated from China National Notifiable Infectious Disease
      Reporting Information System, and the data of epidemiological investigation for
      individual P. vivax case (imported and indigenous) during 2011-2014 were
      collected from China Parasite Disease Prevention and Control Information System.
      All of the data didn't include China's Hongkong, Macao, Taiwan and foreign cases.
      The risk factors on hospitalization were explored by multiple factors variable
      binary classification unconditioned logistic regression model. RESULTS: During
      study period of four years, a total of 5 656 Plasmodium vivax cases were
      detected. Among them, 69.9% (3 951 cases) were imported cases and 30.1% (1 705
      cases) were autochthonous cases. The male cases accounted for 82.7% of all cases.
      Among the autochthonous cases, 535 cases (31.4%) occurred in the cross-bordering
      areas, and 577 cases (33.8%) were reported in the junction of difference
      provinces. The amount of autochthonous cases decreased from 1 363 cases in 2011
      to 53 cases in 2014, and the county affected by autochthonous cases was shrunk
      from 185 counties to 10 counties. The proportion of autochthonous cases
      introduced by domestic migrants increased constantly, which reached 41.5% in
      2014. The imported cases were detected from 614 counties of 30 provinces, who
      were originated from 57 overseas countries of 4 continents, with Southeast Asia
      being the leading origins (2 772 cases, 70.2%). There were 1 494 cases
      hospitalized for treatment, with the male (OR=1.41, 95%CI: 1.16-1.71), 14 years
      old and younger (OR=2.26, 95%CI: 1.44-3.56), and oversea imported cases (OR=2.73,
      95%CI: 2.30-3.25) were the high risk group for hospitalization. CONCLUSION: The
      scale and scope of P. vivax occurrence decreased dramatically since initiation of
      malaria elimination grogram in 2010. However, the risk of P. vivax introduction
      by the overseas imported cases and domestic migrants should be highlighted.

PMID- 27029361
TI  - [Epidemiologic characteristics of Plasmodium ovale in China in 2011-2014].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of Plasmodium ovale
      in 2011-2014 for malaria control policy making during the phase of malaria
      elimination in China. METHODS: The data of individual Plasmodium ovale case
      (probable and confirmed) and population during 20011-2014 were collated from
      China National Notifiable Infectious Disease Reporting Information System, and
      the data of epidemiological investigation for individual Plasmodium ovale case
      (imported and indigenous) during 2011-2014 were collected from China Parasite
      Disease Prevention and Control Information System. All of the data didn't include
      China's Hongkong, Macao, Taiwan and foreign cases. The epidemiological
      characteristics, diagnosis and reporting were compared and analyzed. RESULTS:
      During study period of 2011-2014, a total of 373 Plasmodium ovale imported cases
      were reported, with male being 98.4% and median age being 40 years old. Jiangsu
      (100 cases), Guangxi (76 cases), Henan (55 cases), Anhui (28 cases) and
      Shandong(18 cases) reported Plasmodium ovale imported cases ranked the top 5
      place in the list. Totally 182 counties from 21 provinces were reported
      Plasmodium ovale imported cases. 94.6% of ovale malaria imported cases (353/373)
      got infected from African countries and comprehensive hospitals, CDCs and
      hospital of infectious disease reported 40.0%, 37.8%, and 16.6% of Plasmodium
      ovale imported cases, respectively. 4 days of median time lag of Plasmodium ovale
      imported cases from date of onset to diagnosis was longer than 3 days.
      CONCLUSION: From 2011 to 2014, the rising number of Plasmodium ovale imported
      cases reported from wilder scope of China. Diagnosis time lag of Plasmodium ovale
      was longer than that of other Plasmodium. Diagnosis and prompt treatment of
      Plasmodium ovale imported cases and relapse case should be highlighted.

PMID- 27029362
TI  - [Long-term effect of environmental cadmium exposure on human body's mineral
      metabolic balance].
AB  - OBJECTIVE: To investigate the effect of long-term exposure to environmental
      cadmium on eight mineral element's metabolic balance of human body. METHODS: To
      choose a high cadmium area polluted by smelting and mining north of Guangdong
      province and a cadmium-free area with a similar economic level, and living and
      eating habit of residents as a contrast from April 2011 to August 2012.
      Stratified random sampling and clustered sampling method were adopted to choose
      the non-occupationally cadmium-exposed respondents who have lived in local area
      for more than 15 years, older than 40 years, having local rice and vegetable as
      the main dietary source, with simple and relatively stable diet, and without
      diabetes, kidney disease, thyroid disease, liver disease or other history of
      chronic disease. This study included 298 respondents, of whom 155 were in cadmium
      exposure group and 143 in control group. Questionnaires was used to acquire their
      health status and their morning urine samples were collected. Electrolytically
      coupled plasma mass spectrometry (ICP-MS) was used to test the concentrations of
      sodium(Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper
      (Cu), zinc (Zn) and iodine (I). The Mann-Whitney U test method was used to
      compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca,
      Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group
      and control group.chi(2) test was used to compare the abnormal rate of urinary
      cadmium between exposed group and control group. Pearson correlation and multiple
      regression method were used to investigate the relationship between urinary
      cadmium levels, gender, age, smoking, passive smoking, and minerals. RESULTS: The
      urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68)
      MUg/g.cr, which was higher than that of the control group, which was 1.69 (1.22
      2.36) MUg/g.cr (Z=-10.49,P<0.001). The abnormal rate of urinary cadmium was 51.6%
      (80/155), which was higher than that of the control group (2.8 %(4/143)) (chi(2)=
      87.56, P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed
      group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15),
      and 246.94 (203.65-342.97) MUg/g.cr, which were higher than those in control
      group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and
      213.85 (156.70-281.63) MUg/g.cr, respectively) (Z values were-4.33,-5.04,-3.47
      and-4.24, all P values <0.001). The urinary P, K level P50 (P25-P75) of exposed
      group were 582.50 (463.20-742.8), 890.10(666.00-1 305.40) MUg/g.cr, which were
      lower than control group (694.50 (546.20-851.17), 1 098.58(904.53-1 479.18)
      MUg/g.cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results
      of Pearson correlation analysis, urinary cadmium was positively correlated with
      urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61,
      0.38, and 0.25, respectively (all P values <0.05). Based on the results of
      multiple regression analysis, urinary cadmium levels contributed most to the
      metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression
      coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001).
      CONCLUSION: Long-term environmental exposure to cadmium affected the metabolic
      balance of Ca, Cu, Zn and I in human body.

PMID- 27029363
TI  - [Cadmium burden and renal dysfunction among residents in cadmium-polluted areas:
      A 3-year follow-up study].
AB  - OBJECTIVE: To investigate dynamic change of cadmium body burden and renal
      dysfunction among residents living in cadmium-polluted areas. METHODS: From April
      to July of 2011, the cadmium-polluted areas of northern Guangdong province in
      China was chosen as the study site. Based on the levels of cadmium pollution in
      soil and rice, the survey areas were divided into low exposed group (average
      concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil,
      respectively) and high exposed group (average concentration of cadmium was >0.40
      mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and
      cluster sampling method of epidemiological investigations were carried out among
      414 local residents who lived in cadmium exposure areas for more than 15 years,
      aged above 40, and without occupational cadmium exposure, including 168 and 246
      residents in low and high exposed group, respectively. From March to June of
      2014, 305 respondents of those who participated in 2011 were successfully traced,
      including 116 and 189 respondents in low and high exposed group, respectively. We
      used health questionnaires to acquire their health status. Home-harvested rice
      and vegetable samples were collected using quartering method for detection of
      cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190
      rice samples, 153 vegetable samples in 2014. Urine specimens of residents were
      collected for the detection of urinary cadmium and creatinine as well as renal
      dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG) and beta2
      microglobulin (beta2-MG), respectively. In 2011 and 2014, Chi-square test was
      used to investigate the differences of abnormality of cadmium concentration in
      rice, vegetables and urinary cadmium, beta2-MG, and NAG that were expressed as
      odds ratio(OR) and 95% confidence intervals (95%CI). RESULTS: In 2011 and 2014,
      cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg, and 0.42
      (0.20-1.14) mg/kg, respectively (Z=-0.77,P=0.440). In 2011 and 2014, cadmium
      concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg, and
      0.25(0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and
      60.8%(93/153), respectively. In 2014, both average concentration and abnormal
      rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69, P<0.001
      and chi(2)=15.58,P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in
      high exposed group were 7.90 (3.96-14.91) MUg/g creatinine, 8.64 (4.56-17.60)
      MUg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011,
      urinary cadmium of high exposed group was significantly increased in 2014 (Z=
      2.80, P=0.005). In 2011 and 2014, concentrations of beta2-MG, NAG P50 (P25-P75)
      were 0.15(0.07-0.29) MUg/g creatinine, 0.15 (0.07-0.45) MUg/g creatinine, and
      7.12 (5.05-10.65) U/g creatinine, 13.55(9.1-19.84) U/g creatinine, respectively,
      with abnormal rates of 7.5% (23/305), 15.1% (46/305), 8.2% (25/305) , and 33.8%
      (103/305), respectively. Compared with baseline in 2011, average concentrations
      of beta2-MG, NAG significantly increased in 2014 (Z=-2.263, P=0.024 and Z=-12.52,
      P<0.001), and abnormal rates of beta2-MG, NAG were also higher in 2014
      (chi(2)=15.61 , P<0.001 and chi(2)=64.72, P<0.001), with odds ratio(OR) of 2.00
      (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). CONCLUSION: Environmental cadmium
      pollution of crops such as rice and vegetables in survey areas continued to
      remain high. Body burden of cadmium might kept at sustainably high levels and
      renal dysfunction was worsened after continuous, long-term cadmium exposure. Our
      results suggested that NAG might be more sensitive than beta2-MG to serve as an
      indicator for an individual's future tubular function.

PMID- 27029364
TI  - [Body mass index, waist circumference and waist-to-height ratio associated with
      the incidence of type 2 diabetes mellitus: a cohort study].
AB  - OBJECTIVE: To investigate the association between body mass index (BMI), waist
      circumference (WC), waist-to-height ratio (WHtR), and the incidence risk of type
      2 diabetes mellitus (T2DM). METHODS: In total, 20 194 participants >=18 years old
      were selected randomly by cluster sampling from two township (town) of the county
      in Henan province from July to August of 2007 and July to August of 2008 and the
      investigation included questionnaires, anthropometric measurements, fasting
      plasma glucose, and lipid profile examination were performed at baseline; 17 236
      participants were enrolled in this cohort study. 14 720 (85.4%) were followed up
      from July to August 2013 and July to October 2014. Finally, 11 643 participants
      (4 301 males and 7 342 females) were included in this study. Incidence density
      and Cox proportional hazards regression models were used to evaluate the risk of
      T2DM associated with baseline BMI, WC, WHtR, and their dynamic changes. RESULTS:
      After average of 6.01 years following up for 11 643 participants, 613 developed
      T2DM and the incidence density was 0.89 per 100 person-years. After adjusted for
      baseline sex, age, smoking, drinking, family history of diabetes, as well as the
      difference of fasting plasma-glucose (FPG), total cholesterol (TC), triglyceride
      (TG), high density lipoprotein cholesterol (HDL-C), systolic blood pressure
      (SBP), diastolic blood pressure (DBP) between baseline and follow-up, Cox
      Proportional-Hazards regression analysis indicated that T2DM risk of baseline BMI
      overweight group, BMI obesity group, abnormal WC group and abnormal WHtR group
      were significantly higher than that of the corresponding baseline normal groups ,
      and the incidence risk of T2DM reached the highest for those whose baseline BMI,
      WC and WHtR were all abnormal, the corresponding HR (95%CI) were 2.05 (1.62
      2.59), 3.01 (2.33-3.90), 2.34 (1.89-2.90), 2.88 (2.21-3.74), 3.32 (2.50-4.40),
      respectively. Whether baseline BMI/WC was normal or not, T2DM risk increased if
      baseline WHtR was abnormal, and the HR (95%CI) of baseline normal BMI/abnormal
      WHtR group, baseline abnormal BMI/abnormal WHtR group, baseline normal
      WC/abnormal WHtR group, baseline abnormal WC/abnormal WHtR group were 1.88 (1.29
      2.74), 3.08 (2.34-4.05), 2.15(1.53-3.00), 3.22 (2.45-4.23), respectively. The
      analysis for dynamic changes of BMI, WC, and WHtR indicated that in baseline
      normal WC or WHtR group, T2DM risk increased when baseline normal WC or WHtR
      developed abnormal at follow-up, and the corresponding HR (95%CI) were 1.79 (1.26
      2.55), 2.12(1.32-3.39), respectively. In baseline abnormal WC or WHtR group, T2DM
      risk decresed when baseline abnormal WC or WHtR reversed to normal at follow-up,
      and the corresponding HR (95%CI) were 2.16 (1.42-3.29), 2.62 (1.63-4.20),
      respectively. CONCLUSION: BMI, WC, and WHtR were associated with increased T2DM
      risk. The more abnormal aggregation of BMI, WC, and WHtR presents, the higher
      T2DM risk was. T2DM risk could be decreased when abnormal WC or WHtR reversed to
      normal.

PMID- 27029365
TI  - [Factors associated with adherence of highly active antiretroviral therapy among
      386 HIV/AIDS patients in 3 provinces of China].
AB  - OBJECTIVE: To investigate adherence and the influence factors among patients who
      are on antiretrovirus therapy (ART) of 3 provinces in China. METHODS: This study
      selected 18-year-old and older AIDS patients as the survey objects who initiated
      anti-retrovirus therapy between April and September of 2014 and kept on the
      treatment for one year in Yunnan,Sichuan,and Hu'nan province. Information of
      demography, treatment and social support was collected by questionnaires. Adopt
      SSRS questionnaire to calculate the information of objective support, subjective
      support and utilization of social support. chi(2) test and logistic regression
      were performed to examine relationships between factors and adherence. RESULTS: A
      total of 386 patients with medication were investigated. Among them, there were
      365 (94.6%) cases who were compliant to the ART, and 357 (92.5%) cases can take
      their pills on time, and 29 (7.5%) cases take their medication in excess of the
      prescribed time more than two hours. Social support score was 27.2 +/- 7.3,
      including objective support score (5.6 +/- 2.7), subjective support score (16.1
      +/- 4.8), and utilization of social support (5.5 +/- 1.9). Multivariate logistic
      regression analysis revealed that adherence was significantly associated with the
      correct cognition of medication (OR (95%CI): 3.24 (1.17-9.00)), the self
      awareness of the drug regimen was not complexity (OR (95%CI): 9.34 (3.27-26.68)),
      taking medication 1 time a day (OR (95%CI): 4.00 (1.35-11.84)), and the batter
      utilization of social support (OR (95%CI): 1.49 (1.06-2.01)). Married/cohabiting
      or farmers tend to be nonadherenced, while the OR (95%CI) was 0.24 (0.08-0.67)
      and 0.23 (0.08-0.69), respectively. CONCLUSION: The patients among these
      provinces were compliant to the ART, and most of them can take their pills on
      time. The social support score of these patients was lower than normal person.
      Participants who have correct cognition of medication, thinking their drug
      regimen was not complexity; Taking medication 1 time a day or have high level of
      utilization of social support showed a significantly higher level of self
      reported adherence.

PMID- 27029366
TI  - [Quality of life and its related factors among HIV/AIDS patients from HIV
      serodiscordant couples in Zhoukou of Henan province].
AB  - OBJECTIVE: To investigate the quality of life and its related factors among
      HIV/AIDS patients from HIV serodiscordant couples in Zhoukou city of Henan
      province. METHODS: During January to May in 2015, by the convenience sample,
      World Health Organization Quality of Life Questionnaire for Brief Version (WHOQOL
      BREF) (Chinese version) and a self-edited questionnaire were used to investigate
      1 251 HIV/AIDS patients who were confirmed with HIV positive by local CDC,
      registered in"HIV serodiscordant family" and agreed to participate in a face-to
      face interview with above 18 year-old based on the local CDC , township hospitals
      and village clinics of 9 counties and 1 district of Zhoukou city, excluding the
      HIV/AIDS patients who were in divorce, death by one side, unknowing about his HIV
      status, with mental illness and disturbance of consciousness, incorrectly
      understanding the content of the questionnaire, and reluctant to participate in
      this study. The scores of quality of life of physical, psychological, social
      relations, and environmental domain were calculated. The related factors of the
      scores of different domains were analyzed by Multiple Two Classification
      Unconditioned Logistic Regression. RESULTS: The scores of investigation objects
      in the physical, psychological, social relations, and environmental domain were
      12.00+/- 2.02, 12.07 +/- 2.07, 11.87 +/- 1.99, and 11.09 +/- 1.84, respectively.
      The multiple Unconditioned Logistic Regression analysis indicated that age <40
      years, on ART and no other sickness in last two weeks were beneficial factors
      associated with physical domain with OR (95%CI): 0.61 (0.35-1.06), 0.52 (0.30
      0.90), and 1.66 (1.09-2.52), respectively. The possibility of no poverty and no
      other sickness in last two weeks increased to 0.15(0.09-0.26) and 1.57(1.06-2.33)
      times of those who was in poverty and with other sickness in last two weeks in
      physical domain. The possibility of participants who were below 40 years old and
      with children increased to 0.58 (0.34-0.98) and 0.37 (0.23-0.57) times of who
      were above 40 years old and without children in psychological domain. The factors
      of with AIDS related symptoms, no children and with other sickness in last two
      week were found to be significantly associated with environmental domain with OR
      (95%CI): 0.65 (0.48-0.88), 0.66 (0.51-0.85), and 0.65 (0.51-0.84), respectively .
      CONCLUSION: The scores of every domain of quality of life in HIV serodiscordant
      couples of Zhoukou city were good. Age, whether having AIDS related symptoms,
      whether to accept ART , children, status of poverty, and whether suffering from
      other diseases in last two weeks were the main factors associated with the
      quality of life.

PMID- 27029367
TI  - [Analysis of the reported data of national rural cervical cancer screening
      project from 2012 to 2013, China].
AB  - OBJECTIVE: To analyze the reported data of national rural cervical cancer
      screening project from 2012 to 2013 and to evaluate the project implementation
      condition. METHODS: Data of the national breast carcinoma and cervical cancer
      (two-cancer) screening project for rural women were collected from the online
      report system of key women and children's public health service programs.The
      screening items included: preliminary screening of cervical lesions (cervical
      cytology, using Traian Bethesda System(TBS) or Pap grading for classification and
      reporting), acetate/iodide staining (VIA/VILI), colposcopy, histopathological
      examination, and pathological diagnosis. The study collected the quarterly
      reported data from 1 183 counties of 30 provinces in 2014 and 1 130 counties of
      30 provinces in 2013. Chi-square test was used to test the difference of positive
      detection rate, as well as precancerous cervical lesions, and cervical cancer
      detection rates among difference preliminary screening methods in 2012 and 2013.
      RESULTS: In 2012 and 2013, the number of cervical cancer screening was 10 621 482
      and 10 321 835. The percentage of using ThinPrep cytological test as the
      screening method was 77.17% (n=8 196 627) and 77.07% (n=7 954 949) in 2012 and
      2013, respectively. Among these ThinPrep cytological tests in these two years,
      65.49% (n=5 368 194) and 71.67% (n=5 701 033) used TBS report system. The
      abnormality rate of colposcopy increased from 27.29% (170 063/623 161) to 31.15%
      (203 397/652 935) (chi(2)=2 295.94,P<0.001). The abnormality rate of
      histopathology test increased from 19.54% (37 992/194 394) to 35.43% (59 004/166
      518) (chi(2)=11 523.58, P<0.001). All together, 27 341 cervical cancer or
      precancerous lesions have been detected in these two years. The detection rate of
      invasive cervical cancer increased from 18.02/100 000 in 2012 to 19.71/100 000
      (chi(2)=7.90,P=0.005) in 2013 and that of precancerous lesions rose from
      106.85/100 000 to 119.26/100 000 (chi(2)=70.82,P<0.001). The early detection rate
      was 89.60% (11 883/13 263), and 89.57% (12 609/14 078), respectively in 2012 and
      2013. In these two years, the rank of the detection rate of each cervical lesion
      were CIN1, CIN2, CIN3, invasive carcinoma, adenocarcinoma in situ, and
      microinvasive carcinoma, from the highest rate to the lowest rate. CONCLUSION:
      The program has achieved certain screening effect and the screening method has
      been improved. However, the quality of colposcope and histopathology should be
      enhanced.

PMID- 27029368
TI  - [Tetracycline-inducible replications of wild-type and an adefovir-dipivoxil
      resistant hepatitis B virus in human liver cells].
AB  - OBJECTIVE: To establish cell lines with inducible replications of wild-type or
      rtE218G, an adefovir-dipivoxil-resistant HBV mutant. METHODS: Tetracycline
      transactivator (tTA) was stably transfected into human liver cell line HepG2.1.2
      folds of full-length of wild-type or rtE218G-mutated HBV genomes were cloned into
      the pTRE vector and cotransfected into the tTA-expressing cells with a linear
      selection marker for hygromycin, respectively. After hygromycin screening, clones
      with the highest levels of tetracycline-inducible HBV replications were selected.
      The obtained cell lines were further used to evaluate the in vitro sensitivity of
      rtE218G mutant to adefovir-dipivoxil. RESULTS: HepG2-off23, a HepG2-derived cell
      line with stable tTA expression was established. PTRE-based plasmids carrying
      wild-type HBV (pTRE-HBV-WT) or rtE218G mutant (pTRE-HBV-E218GHBV) were
      constructed. After stable transfection of the HBV constructs into HepG2-off23
      cells, cell lines with robust and tetracycline-inducible replications of wild
      type HBV (HepG2-tetHBV-WT) and rtE218G-mutated HBV (HepG2-tetHBV-E218G) were
      selected. In the two cell lines, high levels of viral core protein and DNA
      replication could be detected after 144 hours of culture, which could be potently
      inhibited when tetracycline was added into the medium. At the presence of 1 000
      ng/ml of tetracycline, HBV replication intermediates were hardly detected by
      Southern blotting experiments. HBV mutant with rtE218G could independently confer
      resistance to adefovir in vitro. IC50 for HBV rtE218G mutant of adefovir was
      (6.49+/-0.09) MUmol/L, which was significantly higher than that for wild type
      virus (2.49+/-0.05) MUmol/L. CONCLUSION: Wild-type and the rtE218G HBV mutant
      could be expressed and efficiently regulated by tetracycline in the established
      new cell lines. These cell lines could be useful tools for the HBV virology and
      anti-HBV drug screening studies.

PMID- 27029369
TI  - [Analysis of 8-hydroxy-2'-deoxyguanosine in human urine by ultra-high performance
      liquid chromatography mass spectrometer method].
AB  - OBJECTIVE: To develop an ultra-high performance liquid chromatography mass
      spectrometer method for the rapid determination of 8-hydroxy-2'-deoxyguanosine (8
      OHdG) in human urines. METHODS: 8-OHdG standard solution with the concentration
      from 0.01 to 0.1 MUg/ml was formulated. The solution was implanted into ion
      source with a rate of 7 MUl/min, the mass-to-charge ratio of parent ion and
      product ions, and ion mass to charge ratio was identified. The mass spectrum
      parameters of each Ion pairs, such as DP, EP and EXP, were gradually optimized.
      The urine sample with a concentration of 10.0 MUg/L was detected, and the pH of
      the sample was adjusted using 1 mol/L ammonium formate and formic acid solution
      with a volume ratio of 5?1, 4?1, 3?1, 2?1, and 1?1. It was tested using three
      different polarity of SPE, i.e.: HLB, MCX, and MAX. The elution effect of
      methanol and water mixture with the proportion of 90?10, 80?20, 50: 50, 20: 80,
      and 10: 90 were tested, and then acetonitrile and water mixture with the
      proportion of 90?10, 80?20, 50?50, 20?80, 10?90 were also tested. The standard
      curve was constructed using the ratio of a standard series application fluid
      concentration to corresponding compounds quantitative ion liquid concentration of
      the peak area. The detection limit was determined as 3 times of the signal to
      noise ratio corresponding to the concentration of 8-OHdG, and the quantitative
      lower limit was determined as 10 times of the signal to noise ratio corresponding
      to the concentration of 8-OHdG. The blank urine spiked recovery method was used
      to evaluate the precision and recovery rate. RESULTS: The mass to charge ratio of
      parent ion was 284.1 and the product ions was 168.1, 140.1, 123.0, and 112.0,
      respectively. The collision voltage of quantitative ion-pair 284.1/168.1 was 18
      V, the 284.1/140.1 collision voltage was 42 V, the 284.1/123.0 collision voltage
      was 48 V, and the 284.1/112.0 collision voltage was 53 V. The recovery rate was
      the highest (87.9%-104.3%) when the pH of urine was adjusted by a 10 ml 1 mol/L
      ammonium formate solution, 2 ml of formic acid, 88 ml of water are mixed with the
      sample solution volume ratio of 1?5, and then purified with 3 ml of methanol and
      3 ml water activated HLB extraction column. Within 1.0-100.0 MUg/L concentration
      range, 8-OHdG standard application solution test results showed a good linear
      relationship. The regression equation was y= 1.25x+0.74, and the correlation
      coefficient was r=0.999 5. The detection limit was 0.2 MUg/L, and the limit of
      quantification was 0.7 MUg/L. The method of recovery rate was in the range of
      87.9% to 104.3%, the precision was in the range from 1.5% to 3.7% and inter-assay
      precision was in the range from 1.6% to 5.4%. CONCLUSION: The method developed in
      this study had high sensitivity, good precision and accuracy, and a wide range of
      testing concentrations.

PMID- 27029370
TI  - [Epidemiological characteristics of severe fever with thrombocytopenia syndrome
      in Liaoning province, 2010-2013].

PMID- 27029371
TI  - [The survey of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzo-p
      furans and dioxin-like polychlorinated bophenyls in twenty-eight market beef].

PMID- 27029372
TI  - [Exploration and practice of the integrated problem-based learning teaching mode
      in public health].

PMID- 27029373
TI  - [Establishing process assessment system in integrated public health problem-based
      learning course].

PMID- 27029374
TI  - [Study on learning experiences and influence factors of public health problem
      based learning course].

PMID- 27029375
TI  - [Writing problem-based learning case and analyzing common problems of public
      health].

PMID- 27029376
TI  - [Research progress of the mechanisms underlying cadmium-induced carcinogenesis].
AB  - Since cadmium is an indirect genotoxic carcinogen, epigenetic modifications could
      be one of the major mechanisms underlying cadmium-induced carcinogenesis. It has
      been proposed that epigenetic alterations might be associated with cadmium
      induced carcinogenesis, such as disruptions of DNA methylation, histone
      modifications, and microRNA expression profile, which would result in abnormal
      expression of carcinogenesis-related genes and/or imbalance of signal
      transduction pathways. Other mechanisms of cadmium-induced carcinogenesis consist
      of disruption of gene regulation and signaling pathways, repression of DNA
      repair, suppression of apoptosis, induction of oxidative stress and autophagy.
      Here, we reviewed the research of both epigenetic and non-epigenetic mechanisms
      underlying cadmium-induced carcinogenesis. 

PMID- 27029377
TI  - The effect of noise-induced variance on parameter recovery from reaction times.
AB  - BACKGROUND: Technical noise can compromise the precision and accuracy of the
      reaction times collected in psychological experiments, especially in the case of
      Internet-based studies. Although this noise seems to have only a small impact on
      traditional statistical analyses, its effects on model fit to reaction-time
      distributions remains unexplored. RESULTS: Across four simulations we study the
      impact of technical noise on parameter recovery from data generated from an ex
      Gaussian distribution and from a Ratcliff Diffusion Model. Our results suggest
      that the impact of noise-induced variance tends to be limited to specific
      parameters and conditions. CONCLUSIONS: Although we encourage researchers to
      adopt all measures to reduce the impact of noise on reaction-time experiments, we
      conclude that the typical amount of noise-induced variance found in these
      experiments does not pose substantial problems for statistical analyses based on
      model fitting.

PMID- 27029378
TI  - Synergistic Therapy of Doxorubicin and miR-129-5p with Self-Cross-Linked
      Bioreducible Polypeptide Nanoparticles Reverses Multidrug Resistance in Cancer
      Cells.
AB  - Although microRNAs (miRs) are short endogenous noncoding RNAs playing a central
      role in cancer initiation and progression, their therapeutic potential in
      overcoming multidrug resistance (MDR) remains unclear. In the present study, we
      developed self-cross-linked biodegradable poly(ethylene glycol)-b-poly(l-lysine)
      b-poly(l-cysteine) (LCss) polypeptide nanoparticles to codeliver DOX and miR-129
      5p, which aimed to overcome MDR in cancer cells. The results showed that LCss
      nanoparticles effectively coencapsulated DOX and miR with great stability, but
      quickly disassembled and released their payload in a bioreducible environment.
      The codelivery of miR-129-5p and DOX with LCss (DLCss/miR) significantly
      increased miR-129-5p expression over 100-fold in MCF-7/ADR cells, which
      effectively overcame MDR by directly inhibiting P-glycoprotein (P-gp), thereby
      increasing intracellular DOX accumulation and cytotoxicity in MCF-7/ADR cells.
      Furthermore, miR-129-5p also partially diminished cyclin-dependent kinase 6
      (CDK6), and synergized with DOX to simultaneously decrease S phase and induce G2
      phase cell cycle arrest, thereby further enhancing the chemosensitivity of MCF
      7/ADR cells. Hence, redox-responsive LCss nanoparticles are potent nanocarrier
      for combinational drug-miR therapy, which could be a promising strategy to
      overcome MDR in cancer cells.

PMID- 27029379
TI  - The CO Photodissociation and Recombination Dynamics of the W172Y/F282T Ligand
      Channel Mutant of Rhodobacter sphaeroides aa3 Cytochrome c Oxidase.
AB  - In the ligand channel of the cytochrome c oxidase from Rhodobacter sphaeroides
      (Rs aa3 ) W172 and F282 have been proposed to generate a constriction that may
      slow ligand access to and from the active site. To explore this issue, the
      tryptophan and phenylalanine residues in Rs aa3 were mutated to the less bulky
      tyrosine and threonine residues, respectively, which occupy these sites in
      Thermus thermophilus (Tt) ba3 cytochrome oxidase. The CO photolysis and
      recombination dynamics of the reduced wild-type Rs aa3 and the W172Y/F282T mutant
      were investigated using time-resolved optical absorption spectroscopy. The
      spectral changes associated with the multiple processes are attributed to
      different conformers. The major CO recombination process (44 MUs) in the
      W172Y/F282T mutant is ~500 times faster than the predominant CO recombination
      process in the wild-type enzyme (~23 ms). Classical dynamic simulations of the
      wild-type enzyme and double mutant showed significant structural changes at the
      active site in the mutant, including movement of the heme a3 ring-D propionate
      toward CuB and reduced binuclear center cavity volume. These structural changes
      effectively close the ligand exit pathway from the binuclear center, providing a
      basis for the faster CO recombination in the double mutant.

PMID- 27029380
TI  - Altered Cytoskeleton as a Mitochondrial Decay Signature in the Retinal Pigment
      Epithelium.
AB  - Mitochondria mediate energy metabolism, apoptosis, and aging, while mitochondrial
      disruption leads to age-related diseases that include age-related macular
      degeneration. Descriptions of mitochondrial morphology have been non-systematic
      and qualitative, due to lack of knowledge on the molecular mechanism of
      mitochondrial dynamics. The current study analyzed mitochondrial size, shape, and
      position quantitatively in retinal pigment epithelial cells (RPE) using a
      systematic computational model to suggest mitochondrial trafficking under
      oxidative environment. Our previous proteomic study suggested that prohibitin is
      a mitochondrial decay biomarker in the RPE. The current study examined the
      prohibitin interactome map using immunoprecipitation data to determine the
      indirect signaling on cytoskeletal changes and transcriptional regulation by
      prohibitin. Immunocytochemistry and immunoprecipitation demonstrated that there
      is a positive correlation between mitochondrial changes and altered filaments as
      well as prohibitin interactions with kinesin and unknown proteins in the RPE.
      Specific cytoskeletal and nuclear protein-binding mechanisms may exist to
      regulate prohibitin-mediated reactions as key elements, including vimentin and
      p53, to control apoptosis in mitochondria and the nucleus. Prohibitin may
      regulate mitochondrial trafficking through unknown proteins that include 110 kDa
      protein with myosin head domain and 88 kDa protein with cadherin repeat domain.
      Altered cytoskeleton may represent a mitochondrial decay signature in the RPE.
      The current study suggests that mitochondrial dynamics and cytoskeletal changes
      are critical for controlling mitochondrial distribution and function. Further,
      imbalance of retrograde versus anterograde mitochondrial trafficking may initiate
      the pathogenic reaction in adult-onset neurodegenerative diseases.

PMID- 27029381
TI  - Seasonal differences in the subjective assessment of outdoor thermal conditions
      and the impact of analysis techniques on the obtained results.
AB  - Wide research attention has been paid in the last two decades to the thermal
      comfort conditions of different outdoor and semi-outdoor urban spaces. Field
      studies were conducted in a wide range of geographical regions in order to
      investigate the relationship between the thermal sensation of people and thermal
      comfort indices. Researchers found that the original threshold values of these
      indices did not describe precisely the actual thermal sensation patterns of
      subjects, and they reported neutral temperatures that vary among nations and with
      time of the year. For that reason, thresholds of some objective indices were
      rescaled and new thermal comfort categories were defined. This research
      investigates the outdoor thermal perception patterns of Hungarians regarding the
      Physiologically Equivalent Temperature (PET) index, based on more than 5800
      questionnaires. The surveys were conducted in the city of Szeged on 78 days in
      spring, summer, and autumn. Various, frequently applied analysis approaches
      (simple descriptive technique, regression analysis, and probit models) were
      adopted to reveal seasonal differences in the thermal assessment of people.
      Thermal sensitivity and neutral temperatures were found to be significantly
      different, especially between summer and the two transient seasons. Challenges of
      international comparison are also emphasized, since the results prove that
      neutral temperatures obtained through different analysis techniques may be
      considerably different. The outcomes of this study underline the importance of
      the development of standard measurement and analysis methodologies in order to
      make future studies comprehensible, hereby facilitating the broadening of the
      common scientific knowledge about outdoor thermal comfort.

PMID- 27029382
TI  - The Diagnosis and Treatment of Fibromuscular Dysplasia: An Update for
      Cardiologists.
AB  - OPINION STATEMENT: Fibromuscular dysplasia (FMD) is an arteriopathy of unknown
      etiology which has traditionally been associated with secondary hypertension;
      however, it has garnered increased attention in the cardiology field in the
      recent years because of its potential association with spontaneous coronary
      artery dissection. Cardiologists should be aware that FMD is a polyvascular
      disease which can affect any arterial bed and can result in morbid conditions
      such as chronic headaches, pulsatile tinnitus, stroke from cervical artery
      dissection, and renal infarction from renal artery dissection and has also been
      associated with increased prevalence of arterial aneurysm, including brain
      aneurysm. For these reasons, some experts recommend panvascular imaging from head
      to-pelvis upon diagnosis for screening purposes and targeted imaging surveillance
      after diagnosis. When necessary, endovascular intervention with angioplasty alone
      is the preferred modality, though there are still situations which require
      surgical intervention. Patients with FMD may benefit from a multispecialty team
      approach for optimal treatment.

PMID- 27029383
TI  - Gene expression profiles of putative biomarker candidates in Mycobacterium avium
      subsp. paratuberculosis-infected cattle.
AB  - This study was conducted to analyze the gene expression of prognostic potential
      biomarker candidates using the whole blood of cattle naturally infected with
      ITALIC! Mycobacterium aviumsubsp. ITALIC! paratuberculosis(MAP). We conducted
      real-time PCR to evaluate 23 potential biomarker candidates. Experimental animals
      were divided into four groups based on fecal MAP PCR and serum ELISA. Seven (
      ITALIC! KLRB1, ITALIC! HGF, ITALIC! MPO, ITALIC! LTF, ITALIC! SERPINE1, ITALIC!
      S100A8and ITALIC! S100A9) genes were up-regulated in fecal MAP-positive cattle
      and three ( ITALIC! KLRB1, ITALIC! MPOand ITALIC! S100A9) were up-regulated in
      MAP-seropositive cattle relative to uninfected cattle. In subclinically infected
      animals, 17 genes ( ITALIC! TFRC, ITALIC! S100A8, ITALIC! S100A9, ITALIC! MPO,
      ITALIC! GBP6, ITALIC! LTF, ITALIC! KLRB1, ITALIC! SERPINE1, ITALIC! PIGR, ITALIC!
      IL-10, ITALIC! CXCR3, ITALIC! CD14, ITALIC! MMP9, ITALIC! ELANE, ITALIC! CHI3L1,
      ITALIC! HPand ITALIC! HGF) were up-regulated compared with the control group.
      Moreover, six genes ( ITALIC! CXCR3, ITALIC! HP, ITALIC! HGF, ITALIC! LTF,
      ITALIC! TFRCand ITALIC! GBP6) showed significant differences between experimental
      groups. Taken together, our data suggest that six genes ( ITALIC! LTF, ITALIC!
      HGF, ITALIC! HP, ITALIC! CXCR3, ITALIC! GBP6and ITALIC! TFRC) played essential
      roles in the immune response to MAP during the subclinical stage and therefore
      might be useful as prognostic biomarkers. 

PMID- 27029384
TI  - Community-Based Study of the Relationship Between Social Capital and Cognitive
      Function in Wuhan, China.
AB  - The present study aimed to detect the association between social capital and
      cognitive function in elderly residents with/without mild cognitive impairment
      (MCI) in Wuhan, China. A cross-sectional study was conducted for data collection
      in 2014. A sample of 1156 participants entered the study. Cognitive function was
      assessed using the Chinese version of the Montreal Cognitive Assessment. A
      modified instrument scale was used to measure bonding and bridging social
      capital. The results indicated that participants without MCI had higher social
      capital scores (45.2 +/- 8.3) than those with MCI (37.0 +/- 6.3; P < .001). With
      adjustments for relevant confounders, the multiple logistic regression model
      showed that participants with a bonding social capital score that ranged from 17
      to 24 had an odds ratio (OR) for MCI of 0.38 (95% CI = 0.04-0.79); those with a
      score that ranged from 25 to 32 had an OR for MCI of 0.36 (95% CI = 0.04-0.70);
      and those with scores >=33 had an OR for MCI of 0.25 (95% CI = 0.03-0.53). In
      conclusion, we found a statistically significant inverse association between
      bonding social capital and MCI, which suggests that shortage of social resource
      from homogeneous social networks might be associated with cognitive decline.

PMID- 27029385
TI  - Pioglitazone use and risk of bladder cancer: population based cohort study.
AB  - OBJECTIVE: To determine whether pioglitazone compared with other antidiabetic
      drugs is associated with an increased risk of bladder cancer in people with type
      2 diabetes. DESIGN: Population based cohort study. SETTING: General practices
      contributing data to the United Kingdom Clinical Practice Research Datalink.
      PARTICIPANTS: A cohort of 145,806 patients newly treated with antidiabetic drugs
      between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014. MAIN
      OUTCOME MEASURES: The use of pioglitazone was treated as a time varying variable,
      with use lagged by one year for latency purposes. Cox proportional hazards models
      were used to estimate adjusted hazard ratios with 95% confidence intervals of
      incident bladder cancer associated with pioglitazone overall and by both
      cumulative duration of use and cumulative dose. Similar analyses were conducted
      for rosiglitazone, a thiazolidinedione not previously associated with an
      increased risk of bladder cancer. RESULTS: The cohort generated 689,616 person
      years of follow-up, during which 622 patients were newly diagnosed as having
      bladder cancer (crude incidence 90.2 per 100,000 person years). Compared with
      other antidiabetic drugs, pioglitazone was associated with an increased risk of
      bladder cancer (121.0 v 88.9 per 100,000 person years; hazard ratio 1.63, 95%
      confidence interval 1.22 to 2.19). Conversely, rosiglitazone was not associated
      with an increased risk of bladder cancer (86.2 v 88.9 per 100,000 person years;
      1.10, 0.83 to 1.47). Duration-response and dose-response relations were observed
      for pioglitazone but not for rosiglitazone. CONCLUSION: The results of this large
      population based study indicate that pioglitazone is associated with an increased
      risk of bladder cancer. The absence of an association with rosiglitazone suggests
      that the increased risk is drug specific and not a class effect.

PMID- 27029386
TI  - Long-term Changes in Extreme Air Pollution Meteorology and the Implications for
      Air Quality.
AB  - Extreme air pollution meteorological events, such as heat waves, temperature
      inversions and atmospheric stagnation episodes, can significantly affect air
      quality. Based on observational data, we have analyzed the long-term evolution of
      extreme air pollution meteorology on the global scale and their potential impacts
      on air quality, especially the high pollution episodes. We have identified
      significant increasing trends for the occurrences of extreme air pollution
      meteorological events in the past six decades, especially over the continental
      regions. Statistical analysis combining air quality data and meteorological data
      further indicates strong sensitivities of air quality (including both average air
      pollutant concentrations and high pollution episodes) to extreme meteorological
      events. For example, we find that in the United States the probability of severe
      ozone pollution when there are heat waves could be up to seven times of the
      average probability during summertime, while temperature inversions in wintertime
      could enhance the probability of severe particulate matter pollution by more than
      a factor of two. We have also identified significant seasonal and spatial
      variations in the sensitivity of air quality to extreme air pollution
      meteorology. 

PMID- 27029387
TI  - Efficient isolation and proteomic analysis of cell plasma membrane proteins in
      gastric cancer reveal a novel differentiation and progression related cell
      surface marker, R-cadherin.
AB  - Cell plasma membrane proteins, playing a crucial role in cell malignant
      transformation and development, were the main targets of tumor detection and
      therapy. In this study, CyDye/biotin double-labeling proteomic approach was
      adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and
      paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western
      blotting, and immunohistochemical staining were used to validate the differential
      expression of a novel identified cell surface marker R-cadherin in gastric cancer
      cells and tissues. Clinicopathological study and survival analysis were performed
      to estimate its roles in tumor progression and outcome prediction. Real-time PCR
      and Western blotting showed that the expression level of R-cadherin in gastric
      cancer were significantly lower than non-cancerous epithelial cell and tissues.
      Clinicopathological study indicated that R-cadherin was dominantly expressed on
      cell surface of normal gastric epithelium, and its expression deletion in gastric
      cancer tissues was associated with tumor site, differentiation, lymph node
      metastasis, and pTNM (chi-square test, P < 0.05). Those patients with R-cadherin
      positive expression displayed better overall survivals than negative expression
      group (log-rank test, P = 0.000). Cox multivariate survival analysis revealed
      lacking the expression of R-cadherin was a main independent predictor for poor
      clinical outcome in gastric cancer (RR = 5.680, 95 % CI 2.250-14.341, P < 0.01).
      We have established a fundamental membrane proteome database for gastric cancer
      and identified R-cadherin as a tumor differentiation and progression-related cell
      surface marker of gastric cancer. Lacking the expression of R-cadherin indicates
      poor prognosis in patients with gastric cancer.

PMID- 27029388
TI  - Testis ultrasound in Klinefelter syndrome infertile men: making the diagnosis and
      avoiding inappropriate management.
AB  - OBJECTIVE: To compare the testicular Color Doppler ultrasound (US), hormone
      levels, and histological results from 67 infertile men with Klinefelter syndrome
      (KS), vs. 66 non-KS non-obstructive azoospermic men. METHODS: Scrotal US images
      were collected from 67 infertile KS and 66 non-obstructive, non-KS azoospermic
      men. The testis volume, echotexture, vascularity, and microliths were evaluated
      and graded. We defined the following echo pattern alteration groups: normal,
      striated, coarse, and measurable nodules. The vascularization was classified as
      low, normal, moderate, or strong. Testosterone, follicle-stimulating hormone,
      luteinizing hormone, and inhibin B levels were determined. Large testicular
      nodules were removed. A testicular biopsy and sperm extraction was performed in
      18 of the KS, and all of the 66 non-KS men. RESULTS: The mean testis volume was
      low in the KS, compared to the non-KS patients: i.e., 2 vs. 8 mL (P < 0.0001).
      The distributions in the echotexture groups differed markedly, with coarse or
      nodular patterns in the KS men, and normal/striated patterns in the control
      patients (P < 0.0001). The vascularization and microlithiasis grades were higher
      in the KS patients than the control men (P < 0.0001 and P < 0.001, respectively).
      All of the nodules removed from the KS patients were benign Leydig cell tumors,
      and all of the biopsies showed marked Leydig cell hyperplasia, with
      spermatogenesis in only two patients. The non-KS biopsies were predominantly
      Sertoli cell-only syndrome. CONCLUSIONS: Small testes, with a coarse or nodular
      echotexture, hypervascularization, and microlithiasis are associated with KS. The
      KS nodules were benign Leydig cell tumors/hyperplasias.

PMID- 27029389
TI  - Visor use among National Hockey League players and its relationship to on-ice
      performance.
AB  - OBJECTIVE: To assess the use of half and three-quarter visors among National
      Hockey League (NHL) players and investigate the relationship between skill level
      and on-ice statistics such as points, penalty minutes and ice time and visor use.
      DESIGN: All players who played at least one game during the 2014-2015 NHL season
      were included in the study. Visor usage including three-quarter visor use was
      determined using official in-game images and video. Player information and
      statistics were obtained from a statistical hockey database. A multiple logistic
      regression model was used to study how the different player statistics influenced
      the probability of a player wearing a visor. RESULTS: Visor use was 87.1% among
      all NHL players (N=881) and 81.7% among all non-rookie players (N=612). Players
      who wore a visor were on average younger, played more games during the season,
      had more points, goals, assists and received more playing time. Players who did
      not wear a visor had 3 times more penalty minutes for every 100 min played. Only
      11 (1.2%) players wore a three-quarter visor and these players were much older
      and contributed more to their team's offence when compared with the players who
      wore a one-half visor. CONCLUSIONS: Visor usage in the NHL continues to increase
      independent of new legislation making it mandatory for rookie players to wear a
      visor. Based on the results and the logistic regression model built in the study,
      those players who have the highest risk for not wearing a visor can be identified
      to help establish targeted interventions.

PMID- 27029390
TI  - How to translate clinical trial results into gain in healthy life expectancy for
      individual patients.

PMID- 27029391
TI  - Quantifying the changes in oxygen extraction fraction and cerebral activity
      caused by caffeine and acetazolamide.
AB  - A quantitative estimate of cerebral blood oxygen saturation is of critical
      importance in the investigation of cerebrovascular disease. We aimed to measure
      the change in venous oxygen saturation (Yv) before and after the intake of the
      vaso-dynamic agents caffeine and acetazolamide with high spatial resolution using
      susceptibility mapping. Caffeine and acetazolamide were administered on separate
      days to five healthy volunteers to measure the change in oxygen extraction
      fraction. The internal streaking artifacts in the susceptibility maps were
      reduced by giving an initial susceptibility value uniformly to the structure-of
      interest, based on a priori information. Using this technique, Yv for normal
      physiological conditions, post-caffeine and post-acetazolamide was measured
      inside the internal cerebral veins as YNormal = 69.1 +/- 3.3%, YCaffeine = 60.5
      +/- 2.8%, and YAcet = 79.1 +/- 4.0%. This suggests that susceptibility mapping
      can serve as a sensitive biomarker for measuring reductions in cerebro-vascular
      reserve through abnormal vascular response. The percentage change in oxygen
      extraction fraction for caffeine and acetazolamide were found to be +27.0 +/-
      3.8% and -32.6 +/- 2.1%, respectively. Similarly, the relative changes in
      cerebral blood flow in the presence of caffeine and acetazolamide were found to
      be -30.3% and + 31.5%, suggesting that the cerebral metabolic rate of oxygen
      remains stable between normal and challenged brain states for healthy subjects.

PMID- 27029392
TI  - Hypothesis on the pathogenesis of meningiomas based on coexisting meningioma
      under the bony prominence of the inner table of the skull.

PMID- 27029393
TI  - Post-operative imaging in deep brain stimulation: A controversial issue.
AB  - In deep brain stimulation (DBS), post-operative imaging has been used on the one
      hand to assess complications, such as haemorrhage; and on the other hand, to
      detect misplaced contacts. The post-operative determination of the accurate
      location of the final electrode plays a critical role in evaluating the precise
      area of effective stimulation and for predicting the potential clinical outcome;
      however, safety remains a priority in postoperative DBS imaging. A plethora of
      diverse post-operative imaging methods have been applied at different centres.
      There is neither a consensus on the most efficient post-operative imaging
      methodology, nor is there any standardisation for the automatic or manual
      analysis of the images within the different imaging modalities. In this article,
      we give an overview of currently applied post-operative imaging modalities and
      discuss the current challenges in post-operative imaging in DBS. 

PMID- 27029394
TI  - Novel balloon application for rescue and realignment of a proximal end migrated
      pipeline flex embolization device into the aneurysmal sac: complication
      management.
AB  - The pipeline embolization device (PED) has become a routine firstline option for
      the treatment of an increasing population of intracranial aneurysms at many
      neurovascular centers. Intraprocedural complications during PED deployment, or
      complications associated with migration of the device, are rarely reported
      problems. Significant mismatch in luminal diameter between the inflow vessel and
      the outflow vessel or excessive dragging-stretching of the PED have been related
      to 'watermelon seed' or 'accordion' effects, respectively, resulting in stent
      migration. Here we present a novel balloon technique that was successfully used
      to realign an in situ flow diverting stent that had prolapsed into a large
      aneurysm. This represents a useful salvage technique and should be considered
      when encountering this potential complication.

PMID- 27029395
TI  - Interventional management of high-flow craniofacial vascular malformations: a
      database analysis and review of the literature.
AB  - BACKGROUND: High-flow craniofacial vascular malformations are uncommon, locally
      aggressive lesions that pose a therapeutic challenge. OBJECTIVE: To report our
      experience with the treatment of high-flow craniofacial vascular malformations.
      METHODS: After institutional review board approval was obtained, the
      neurointerventional databases of two institutions were retrospectively reviewed
      for vascular malformations from October 2010 to June 2015. All patients who had
      been treated for a high-flow craniofacial vascular malformation were included in
      the analysis. Clinical presentation, location, type, agent and techniques used,
      procedural complications, and clinical and imaging follow-up were included in the
      analysis. RESULTS: Eighteen patients (12 female and 6 male) harboring 21 high
      flow vascular malformations met the inclusion criteria in our study. All patients
      were symptomatic. One patient had two separated arteriovenous malformations
      (AVMs) (one nasal and the other forehead/scalp), and one patient had three
      separated scalp lesions. One patient with a nasal AVM had capillary malformation
      AVM syndrome. Overall, 13 AVM and 8 arteriovenous fistuli were treated in 31
      targeted embolization procedures (ranging from 1 procedure to 4 procedures, mean
      1.7 procedures). Onyx was the predominant agent used in 25 procedures. In 31
      procedures, 1 procedural complication (skin ulceration) occurred. At the end of
      the last treatment session 14 of the 21 lesions were cured. Symptomatic control
      was achieved in all cases, with resolution or significant improvement of the
      symptoms (mean follow-up of 10 months). CONCLUSIONS: High-flow craniofacial
      vascular malformations can be successfully managed with interventional
      techniques.

PMID- 27029396
TI  - Closure of Secundum Atrial Septal Defects by Using the Occlutech Occluder Devices
      in More Than 1300 Patients: The IRFACODE Project: A Retrospective Case Series.
AB  - BACKGROUND: The Occlutech Figulla ASD device series (OFSO) shows an improved
      device design for interventional ASD closure, larger follow-up series are
      missing. METHODS: We retrospectively reviewed the feasibility, safety,
      implantation properties, results, and follow-up of ASD closure using Occlutech
      devices over a 5 year period by establishing a multi-institutional collaborative
      result registry with 16 contributing centers from 11 countries (IRFACODE).
      RESULTS: In 1315 patients of all age groups (female 66.9%), successful (98%) ASD
      closure was performed (mean age 28.9 years, weight 52 kg, height 148.6 cm). Of
      the defects, 47.9% showed no or only a deficient aortic rim; in 11.9%, there was
      more than one defect; a septum aneurysm was present in 21.5%; and the mean
      implanted device size was 20.5 mm. Immediate closure was achieved in 78.6%, at
      discharge in 83.1%, and 96.4% and 97.3% at 6 and 12 months follow-up,
      respectively. During a mean follow-up of 2.7 years (in total 3597 patient years),
      significant complications were minimal (total = 8, <1%) with secondary device
      embolizations in five and AV-blocks in three patients. No erosion or death was
      reported. CONCLUSION: ASD closure using OFSO is feasible in a large variety of
      patients, safe with only a minimal risk of severe side effects and especially
      without any aortic erosions despite a large percentage of large and complicated
      defects. (c) 2016 Wiley Periodicals, Inc.

PMID- 27029398
TI  - Conductivity tensor of graphene dominated by spin-orbit coupling scatterers: A
      comparison between the results from Kubo and Boltzmann transport theories.
AB  - The diagonal and Hall conductivities of graphene arising from the spin-orbit
      coupling impurity scattering are theoretically studied. Based on the continuous
      model, i.e. the massless Dirac equation, we derive analytical expressions of the
      conductivity tensor from both the Kubo and Boltzmann transport theories. By
      performing numerical calculations, we find that the Kubo quantum transport result
      of the diagonal conductivity within the self-consistent Born approximation
      exhibits an insulating gap around the Dirac point. And in this gap a well-defined
      quantized spin Hall plateau occurs. This indicates the realization of the quantum
      spin Hall state of graphene driven by the spin-orbit coupling impurities. In
      contrast, the semi-classical Boltzmann theory fails to predict such a topological
      insulating phase. The Boltzmann diagonal conductivity is nonzero even in the
      insulating gap, in which the Boltzmann spin Hall conductivity does not exhibit
      any quantized plateau. 

PMID- 27029397
TI  - Noise propagation with interlinked feed-forward pathways.
AB  - Functionally similar pathways are often seen in biological systems, forming feed
      forward controls. The robustness in network motifs such as feed-forward loops
      (FFLs) has been reported previously. In this work, we studied noise propagation
      in a development network that has multiple interlinked FFLs. A FFL has the
      potential of asymmetric noise-filtering (i.e., it works at either the "ON" or the
      "OFF" state in the target gene). With multiple, interlinked FFLs, we show that
      the propagated noises are largely filtered regardless of the states in the input
      genes. The noise-filtering property of an interlinked FFL can be largely derived
      from that of the individual FFLs, and with interlinked FFLs, it is possible to
      filter noises in both "ON" and "OFF" states in the output. We demonstrated the
      noise filtering effect in the developmental regulatory network of Caenorhabditis
      elegans that controls the timing of distal tip cell (DTC) migration. The roles of
      positive feedback loops involving blmp-1 and the degradation regulation of DRE-1
      also studied. Our analyses allow for better inference from network structures to
      noise-filtering properties, and provide insights into the mechanisms behind the
      precise DTC migration controls in space and time. 

PMID- 27029399
TI  - Geographic information system data from ambulances applied in the emergency
      department: effects on patient reception.
AB  - BACKGROUND: Emergency departments (ED) recognize crowding and handover from
      prehospital to in-hospital settings to be major challenges. Prehospital
      Geographical Information Systems (GIS) may be a promising tool to address such
      issues. In this study, the use of prehospital GIS data was implemented in an ED
      in order to investigate its effect on 1) wait time and unprepared activations of
      Trauma Teams (TT) and Medical Emergency Teams (MET) and 2) nurses' perceptions
      regarding patient reception, workflow and resource utilization. METHODS: 
      INTERVENTION: From May 1st 2014 to October 31th 2014, GIS data was displayed in
      the ED. Data included real-time estimated time of arrival, distance to ED,
      dispatch criteria, patient data and ambulance contact information. Data was used
      by coordinating nurses for time activation of TT and MET involved in the initial
      treatment of severely-injured or critically-ill patients. In addition, it was
      used as a logistics tool for handling all other patients transported by ambulance
      to the ED. STUDY DESIGN: The study followed a mixed-methods design, consisting of
      a quantitative study (before and after intervention) and a qualitative study
      (survey and interviews). PARTICIPANTS: Participants included all patients
      received by TT or MET and coordinating nurses in the ED. RESULTS: 1.)
      Quantitative: 599 patients were included. The median wait time for TT and MET was
      5 min both before and after the GIS intervention, showing no difference (p =
      0.18). A significant reduction in the subgroup of waits >10 min was found (p <
      0.05). No difference was found in unprepared TT and MET activations. 2.)
      Qualitative: Nurses perceived GIS data as a tool to optimize resource utilization
      and quality of all patients' reception, critically or non-critically ill. No
      substantial disadvantages were reported. DISCUSSION: The contradiction of
      measured median wait time and nurses perceived improved timing of team activation
      may result from having both RT- ETA and supplemental patient information not only
      for seriously-injured or critically-ill patients received by the TT and MET, but
      for all patients transported by ambulance. The reduction in waits > 10 minutes
      may have contributed to the overall perception of reduced wait time, as avoidance
      of long waits is clinically more important than reduction in the median wait
      time. CONCLUSION: A comparison of the use of prehospital GIS data in the ED with
      the control period showed no effect on median wait time for TT and MET, however,
      the number of waits of >10 min was reduced. On the other hand, nurses perceived
      implementation of GIS data as improving workflow, resource utilization and
      quality of all patients' reception, critically as well as non-critically ill.
      There were no substantial disadvantages to the GIS application. TRIAL
      REGISTRATION: ClinicalTrials.gov (NCT02188966).

PMID- 27029400
TI  - Resilience: synthesis of concept analyses and contribution to nursing
      classifications.
AB  - AIM: To synthetize elements of research on concept analyses of resilience; and to
      propose a definition of resilience to NANDA International (NANDA-I) and
      International Classification for Nursing Practice (ICNP((r)) ). BACKGROUND:
      Nursing classifications represent nursing knowledge that is clinically relevant
      and in continuous development. INTRODUCTION: Nursing is considered holistic and
      there is always the need to consider human responses to health and life
      processes. Continuously there are new and emerging concepts concerning humans and
      health that should be considered within the organization and delivery of health
      care as resilience. METHODS: In March 2015, the authors performed a synthesis of
      the findings of research concept analysis research derived from a systematic
      literature search of electronic databases (PsycINFO, CINAHL and PubMed). Search
      terms used in the title were: 'resilience' AND 'analysis' AND 'concept'. Papers
      written in Portuguese or English were included. FINDINGS: A total of 27 papers
      were identified and eight papers were included. Of these, seven papers used
      Walker & Avant's () model and one used Rodger's () model. Resilience emerged as a
      fundamental concept across the lifespan that is closely related to health and
      well-being. DISCUSSION: Resilience is a phenomenon of interest for nurses.
      Similar attributes, antecedents, consequents and definitions were synthesized
      into a new proposal of a definition of resilience. While some diagnoses related
      to resilience are classified in NANDA-I, the concept is not included in ICNP((r))
      . CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The inclusion of the
      concept into ICNP((r)) and the update in NANDA-I is a contribution for nursing
      knowledge through education and for clinical practice, as this could promote the
      effectiveness of interventions in several contexts.

PMID- 27029401
TI  - Caring for a relative with delusional beliefs: a qualitative exploration.
AB  - WHAT IS KNOWN ON THE SUBJECT?: Delusions are common experiences in psychosis and
      this is reflected in the number of studies focused on improving our understanding
      of their development, impact, and treatments. Many service users with psychosis
      are in informal caregiving relationships and carers can play an instrumental role
      in the recovery process. There remains a lack of knowledge and understanding
      about carer experiences and how they cope when their relative's delusions involve
      them or close others. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Data drawn
      from five individual carer interviews, which were subject to interpretative
      phenomenological analysis, identified the importance of six key themes. In
      addition to a carer's exposure to their relative's illness symptoms and a
      reported lack of understanding about their relative's delusions, was a fear of
      delusion-driven behaviours, and the carer's attempt to conceal the true extent of
      their caregiving challenges to others. Carers' relationships were fractured and
      their coping was best described as an ongoing process, mainly developed through
      trial and error. It extends our understanding of important issues faced by a
      subgroup of carers and facilitates discussion beyond their levels of stress and
      burden. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The study, with its limitations,
      indicates some carers may live in fear of harm from their relatives but also be
      reluctant to disclose to others the full story of what they are coping with.
      Health professionals must routinely assess for risks that informal carers may be
      exposed to as part of their role, and offer tailored support and interventions.
      ABSTRACT: Background In recent years, there has been a gradual shift towards the
      study of individual symptom presentations in psychosis, this is particularly
      found in studies of delusional beliefs. However, the literature remains sparse on
      informal caregiver experiences of individual symptoms. Aim The study sought to
      investigate carer experiences of supporting a relative with delusional beliefs,
      which involve family members. Methods Semi-structured interviews were undertaken
      with five caregivers and subject to interpretative phenomenological analysis.
      Results Interviews yielded six superordinate themes highlighting issues
      concerning a carer's exposure to symptoms of illness; lack of understanding about
      their relatives' delusional beliefs; concerns over coming to harm from their
      relative: efforts made by the carer to conceal their relative's delusional
      beliefs and their consequences; fractured relationships, and a long process of
      learning how to best cope. Conclusion Caring for a relative with psychosis who
      experiences delusional beliefs about the carer and family members can be
      challenging. The results underscore the importance of providing a programme of
      support to meet the varied needs of informal carers with an explicit aim of
      assisting carers in their day-to-day problem solving. It should also help to
      address issues carers may have about causality, including beliefs about self
      blame, and identifying effective coping strategies.

PMID- 27029402
TI  - High emissions of greenhouse gases from grasslands on peat and other organic
      soils.
AB  - Drainage has turned peatlands from a carbon sink into one of the world's largest
      greenhouse gas (GHG) sources from cultivated soils. We analyzed a unique data set
      (12 peatlands, 48 sites and 122 annual budgets) of mainly unpublished GHG
      emissions from grasslands on bog and fen peat as well as other soils rich in soil
      organic carbon (SOC) in Germany. Emissions and environmental variables were
      measured with identical methods. Site-averaged GHG budgets were surprisingly
      variable (29.2 +/- 17.4 t CO2 -eq. ha-1  yr-1 ) and partially higher than all
      published data and the IPCC default emission factors for GHG inventories.
      Generally, CO2 (27.7 +/- 17.3 t CO2  ha-1  yr-1 ) dominated the GHG budget.
      Nitrous oxide (2.3 +/- 2.4 kg N2 O-N ha-1  yr-1 ) and methane emissions (30.8 +/-
      69.8 kg CH4 -C ha-1  yr-1 ) were lower than expected except for CH4 emissions
      from nutrient-poor acidic sites. At single peatlands, CO2 emissions clearly
      increased with deeper mean water table depth (WTD), but there was no general
      dependency of CO2 on WTD for the complete data set. Thus, regionalization of CO2
      emissions by WTD only will remain uncertain. WTD dynamics explained some of the
      differences between peatlands as sites which became very dry during summer showed
      lower emissions. We introduced the aerated nitrogen stock (Nair ) as a variable
      combining soil nitrogen stocks with WTD. CO2 increased with Nair across
      peatlands. Soils with comparatively low SOC concentrations showed as high CO2
      emissions as true peat soils because Nair was similar. N2 O emissions were
      controlled by the WTD dynamics and the nitrogen content of the topsoil. CH4
      emissions can be well described by WTD and ponding duration during summer. Our
      results can help both to improve GHG emission reporting and to prioritize and
      plan emission reduction measures for peat and similar soils at different scales.

PMID- 27029403
TI  - A geological perspective on the degradation and conservation of western Atlantic
      coral reefs.
AB  - Continuing coral-reef degradation in the western Atlantic is resulting in loss of
      ecological and geologic functions of reefs. With the goal of assisting resource
      managers and stewards of reefs in setting and measuring progress toward realistic
      goals for coral-reef conservation and restoration, we examined reef degradation
      in this region from a geological perspective. The importance of ecosystem
      services provided by coral reefs-as breakwaters that dissipate wave energy and
      protect shorelines and as providers of habitat for innumerable species-cannot be
      overstated. However, the few coral species responsible for reef building in the
      western Atlantic during the last approximately 1.5 million years are not thriving
      in the 21st century. These species are highly sensitive to abrupt temperature
      extremes, prone to disease infection, and have low sexual reproductive potential.
      Their vulnerability and the low functional redundancy of branching corals have
      led to the low resilience of western Atlantic reef ecosystems. The decrease in
      live coral cover over the last 50 years highlights the need for study of relict
      (senescent) reefs, which, from the perspective of coastline protection and
      habitat structure, may be just as important to conserve as the living coral
      veneer. Research is needed to characterize the geological processes of
      bioerosion, reef cementation, and sediment transport as they relate to modern-day
      changes in reef elevation. For example, although parrotfish remove nuisance
      macroalgae, possibly promoting coral recruitment, they will not save Atlantic
      reefs from geological degradation. In fact, these fish are quickly nibbling away
      significant quantities of Holocene reef framework. The question of how different
      biota covering dead reefs affect framework resistance to biological and physical
      erosion needs to be addressed. Monitoring and managing reefs with respect to
      physical resilience, in addition to ecological resilience, could optimize the
      expenditure of resources in conserving Atlantic reefs and the services they
      provide.

PMID- 27029404
TI  - Glial cell biology in the Great Lakes region.
AB  - We report on the tenth bi-annual Great Lakes Glial meeting, held in Traverse
      City, Michigan, USA, September 27-29 2015. The GLG meeting is a small conference
      that focuses on current research in glial cell biology. The array of functions
      that glial cells (astrocytes, microglia, oligodendrocytes, Schwann cells) play in
      health and disease is constantly increasing. Despite this diversity, GLG meetings
      bring together scientists with common interests, leading to a better
      understanding of these cells. This year's meeting included two keynote speakers
      who presented talks on the regulation of CNS myelination and the consequences of
      stress on Schwann cell biology. Twenty-two other talks were presented along with
      two poster sessions. Sessions covered recent findings in the areas of microglial
      and astrocyte activation; age-dependent changes to glial cells, Schwann cell
      development and pathology, and the role of stem cells in glioma and neural
      regeneration. 

PMID- 27029406
TI  - Proteomics in thyroid cytopathology: Relevance of MALDI-imaging in distinguishing
      malignant from benign lesions.
AB  - Several proteomic strategies are used extensively for the purpose of biomarker
      discovery and in order to obtain insights into the molecular aspects of cancers,
      using either body fluids or tissue as samples. Among them, MALDI-imaging can be
      applied to cytological thyroid specimens to investigate the molecular signatures
      of different pathological conditions and highlight differences in the proteome
      that are of relevance for diagnostic and pathogenetic research. In this study, 26
      ex-vivo fine needle aspirations from benign thyroid nodules (n = 13) and
      papillary thyroid carcinomas (n = 13) were analyzed by MALDI-imaging. Based on
      the specific protein signatures capable of distinguishing the aforementioned
      patients, MALDI-imaging was able to correctly assign, in blind, the specimens
      from ten additional FNABs to a malignant or benign class, as later confirmed by
      the morphological classification. Moreover, some proteins presented a progressive
      overexpression in malignant phenotypes when compared with Hashimoto's thyroiditis
      and hyperplastic/follicular adenoma. This data not only suggests that a MALDI
      imaging based approach can be a valuable tool in the diagnosis of thyroid lesions
      but also in the detection of proteins that have a possible role in the promotion
      of tumorigenic activity.

PMID- 27029405
TI  - Quaking promotes monocyte differentiation into pro-atherogenic macrophages by
      controlling pre-mRNA splicing and gene expression.
AB  - A hallmark of inflammatory diseases is the excessive recruitment and influx of
      monocytes to sites of tissue damage and their ensuing differentiation into
      macrophages. Numerous stimuli are known to induce transcriptional changes
      associated with macrophage phenotype, but posttranscriptional control of human
      macrophage differentiation is less well understood. Here we show that expression
      levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early
      human atherosclerotic lesions, but are abundant in macrophages of advanced
      plaques. Depletion of QKI protein impairs monocyte adhesion, migration,
      differentiation into macrophages and foam cell formation in vitro and in vivo.
      RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes,
      including those of a unique QKI haploinsufficient patient, reveal striking
      changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts.
      The biological importance of these transcripts and requirement for QKI during
      differentiation illustrates a central role for QKI in posttranscriptionally
      guiding macrophage identity and function. 

PMID- 27029408
TI  - Chronic osteomyelitis increases long-term mortality risk in the elderly: a
      nationwide population-based cohort study.
AB  - BACKGROUND: The elderly are predisposed to chronic osteomyelitis because of the
      immunocompromised nature of aging and increasing number of chronic comorbidities.
      Chronic osteomyelitis may significantly affect the health of the elderly;
      however, its impact on long-term mortality remains unclear. We conceived this
      retrospective nationwide population-based cohort study to address this issue.
      METHODS: We identified 10,615 elderly patients (>=65 years) comprising 965
      patients with chronic osteomyelitis and 9650 without chronic osteomyelitis
      matched at a ratio of 1:10 by age and gender between 1999 and 2010 from the
      Taiwan National Health Insurance Research Database. The risk of chronic
      osteomyelitis between the two cohorts was compared by a following-up until 2011.
      RESULTS: Patients with chronic osteomyelitis had a significantly higher mortality
      risk than those without chronic osteomyelitis [incidence rate ratio (IRR): 2.29;
      95 % confidence interval (CI): 2.01-2.59], particularly the old elderly (>=85
      years; IRR: 3.27; 95 % CI: 2.22-4.82) and males (IRR: 2.7; 95 % CI: 2.31-3.16).
      The highest mortality risk was observed in the first month (IRR: 5.01; 95 % CI:
      2.02-12.42), and it remained persistently higher even after 6 years (IRR: 1.53;
      95 % CI: 1.13-2.06) of follow-up. Cox proportional hazard regression analysis
      showed that chronic osteomyelitis [adjusted hazard ratio (AHR): 1.89; 95 % CI:
      1.66-2.15], advanced age (>=85 years; AHR: 2.02; 95 % CI: 1.70-2.41), male (AHR:
      1.34; 95 % CI: 1.22-1.48), and chronic comorbidities were independent predictors
      of mortality. CONCLUSIONS: This study demonstrated that chronic osteomyelitis
      significantly increased the long-term mortality risk in the elderly. Therefore,
      strategies for prevention and treatment of chronic osteomyelitis and concomitant
      control of chronic comorbidities are very important for the management of the
      elderly, particularly for a future with an increasingly aged population
      worldwide.

PMID- 27029407
TI  - Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication.
AB  - Autophagy is an evolutionarily ancient pathway that has been shown to be
      important in the innate immune defense against several viruses. However, little
      is known about the regulatory role of autophagy in transmissible gastroenteritis
      virus (TGEV) replication. In this study, we found that TGEV infection increased
      the number of autophagosome-like double- and single-membrane vesicles in the
      cytoplasm of host cells, a phenomenon that is known to be related to autophagy.
      In addition, virus replication was required for the increased amount of the
      autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected
      cells, suggesting that TGEV infection triggered a complete autophagic response.
      When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV
      replication increased. The increase in virus yield via autophagy inhibition was
      further confirmed by the use of siRNA duplexes, through which three proteins
      required for autophagy were depleted. Furthermore, TGEV replication was inhibited
      when autophagy was activated by rapamycin. The antiviral response of autophagy
      was confirmed by using siRNA to reduce the expression of gene p300, which
      otherwise inhibits autophagy. Together, the results indicate that TGEV infection
      activates autophagy and that autophagy then inhibits further TGEV replication. 

PMID- 27029409
TI  - Utility of the quadrilobe flap for repairing defects of the nasal tip.
AB  - The quadrilobe flap allows the mobilisation of the skin of the upper nose and
      nasofacial sulcus to the distal nose while avoiding unfavourable tension vectors
      that would distort the free margin of the ala. We report our experience over the
      past 3 years in the first case series of quadrilobe flaps for repair of surgical
      defects on the nose. 

PMID- 27029410
TI  - POSAiDA: presence of Staphylococcus aureus/MRSA and Enterococcus/VRE in Danish
      ambulances. A cross-sectional study.
AB  - BACKGROUND: Every year approximately one out of ten Danish patients contracts a
      healthcare associated infection (HAI). Staphylococcus aureus and Enterococcus are
      prominent in the group of pathogenic bacteria that underlie HAIs, causing
      unnecessary inconvenience and prolonging hospitalization. Bacterial colonization
      often occurs due to indirect patient-to-patient transmission, caused by poor
      hygiene compliance. This study aims to determine the level of contamination with
      S. aureus/MRSA and Enterococcus/VRE on presumed clean blood pressure cuffs in the
      Danish ambulances. METHOD: Blood pressure cuffs were tested for contamination
      with S. aureus and Enterococcus when being cleaned according to everyday
      guidelines in this cross-sectional study. Imprints were performed with specific
      agar plates after cleaning with ethanol wipes. Positive imprints were typed and
      antibiotic susceptibility was determined. RESULTS: Both S. aureus and
      Enterococcus were found on blood pressure cuffs thought to be clean, however, to
      a limited extent. The average level of contamination by S. aureus was 0.54 CFU
      per 25 cm(2) (SD 1.98). Minimum and maximum values ranged from 0 to 12 CFU per 25
      cm(2) and 10% of the 50 samples were positive. The average level of contamination
      by Enterococcus was 0.06 CFU per 25 cm(2) (SD 0.42). Minimum and maximum values
      ranged from 0 to 3 CFU per 25 cm(2) and 2% of the 50 samples were positive. All
      S. aureus isolates were found to be methicillin susceptible S. aureus (MSSA) and
      the one Enterococcus isolate was identified as Enterococcus faecalis, negative
      for vancomycin resistance genes. CONCLUSION: Staphylococcus aureus and
      Enterococcus were detectable on equipment thought to be clean. However, all
      detected bacteria showed susceptibility towards methicillin or vancomycin.
      Findings of pathogens after cleaning may be due to cross-contamination, improper
      cleaning and limited effect of the currently used cleaning procedure and are
      thought to affect the risk of infection. Therefore, we recommend a thorough
      evaluation of current cleaning procedures as well as increased focus on and
      further research into hygiene challenges in a prehospital setting. Future studies
      should be performed in order to demonstrate the level of bacterial contamination
      in all areas of the medical service, e.g., the ambulance environment, medical
      equipment, staff uniform and hand hygiene. Furthermore, in order to establish
      evidence for different cleaning procedures in situ we recommend testing the
      effect of different cleaning interventions by interventional designs.

PMID- 27029411
TI  - Saturn-like charge-transfer complexes Li4&B36, Li5&B36+, and Li6&B362+: exohedral
      metalloborospherenes with a perfect cage-like B364- core.
AB  - Based on extensive first-principles theory calculations, we present the
      possibility of construction of the Saturn-like charge-transfer complexes Li4&B36
      (2), Li5&B36(+) (3), and Li6&B36(2+) (4) all of which contain a perfect cage-like
      B36(4-) (1) core composed of twelve interwoven boron double chains with a sigma +
      pi double delocalization bonding pattern, extending the Bn(q) borospherene family
      from n = 38-42 to n = 36 with the highest symmetry of T(h).

PMID- 27029413
TI  - The VWF-GPIb axis in ischaemic stroke: lessons from animal models.
AB  - Stroke is a leading cause of death and long-term disability worldwide. Ischaemic
      stroke is caused by a blood clot that obstructs cerebral blood flow. Current
      treatment mainly consists of achieving fast reperfusion, either via
      pharmacological thrombolysis using tissue plasminogen activator or via
      endovascular thrombectomy. Unfortunately, reperfusion therapy is only available
      to a limited group of patients and reperfusion injury can further aggravate brain
      damage. Hence, there is an urgent need for better understanding of ischaemic
      stroke pathophysiology in order to develop novel therapeutic strategies. In
      recent years, the pathophysiological importance of von Willebrand factor (VWF) in
      ischaemic stroke has become clear from both clinical and experimental studies. In
      particular, binding of VWF to platelet glycoprotein Ib (GPIb) has become an
      interesting target for ischaemic stroke therapy. Recent insights show that
      inhibting the VWF-GPIb interaction could result in a pro-thrombolytic activity
      improving cerebral reperfusion rates and concurrently reducing cerebral
      ischaemia/reperfusion damage. This review gives an overview of the experimental
      evidence that illustrates the crucial role of the VWF-GPIb axis in ischaemic
      stroke.

PMID- 27029412
TI  - High event-free survival rate with minimum-dose-anthracycline treatment in
      childhood acute promyelocytic leukaemia: a nationwide prospective study by the
      Japanese Paediatric Leukaemia/Lymphoma Study Group.
AB  - We evaluated the efficacy of treatment using reduced cumulative doses of
      anthracyclines in children with acute promyelocytic leukaemia (APL) in the
      Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients
      received two and three subsequent courses of induction and consolidation
      chemotherapy respectively, consisting of all-trans retinoic acid (ATRA),
      cytarabine and anthracyclines, followed by maintenance therapy with ATRA.
      Notably, a single administration of anthracyclines was introduced in the second
      induction and all consolidation therapies to minimize total doses of
      anthracycline. The 3-year event-free (EFS) and overall survival rates for 43
      eligible children were 83.6% [95% confidence interval (CI): 68.6-91.8%] and 90.7%
      (95% CI: 77.1-96.4%), respectively. Although two patients died of intracranial
      haemorrhage or infection during induction phases, no cardiac adverse events or
      treatment-related deaths were observed during subsequent phases. Patients not
      displaying M1 marrow after the first induction therapy, or those under 5 years of
      age at diagnosis, showed inferior outcomes (3-year EFS rate; 33.3% (95% CI: 19.3
      67.6%) and 54.6% (95% CI: 22.9-78.0%), respectively). In conclusion, a single
      administration of anthracycline during each consolidation phase was sufficient
      for treating childhood APL. In younger children, however, conventional ATRA and
      chemotherapy may be insufficient so that alternative therapies should be
      considered.

PMID- 27029414
TI  - Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation
      in experimental hepatopulmonary syndrome.
AB  - BACKGROUND AND AIM: Pulmonary monocyte infiltration plays a significant role in
      the development of angiogenesis in experimental hepatopulmonary syndrome (HPS)
      after common bile duct ligation (CBDL). Hepatic monocytes are also increased
      after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been
      identified as a major source of monocytes that accumulate in injured tissues.
      Whether splenic monocytes contribute to monocyte alterations after CBDL is
      unknown. This study evaluates monocyte distributions and assesses effects of
      splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities
      in experimental HPS. METHODS: Splenectomy was performed in CBDL animals. Monocyte
      levels in different tissues and circulation were assessed with CD68. Pulmonary
      alterations of HPS were evaluated with vascular endothelial growth factor-A (VEGF
      A) levels, angiogenesis, and alveolar-arterial oxygen gradient (AaPO2 ). Liver
      abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation
      (CK-19), and enzymatic changes. RESULTS: Monocyte levels increased in the lung
      and liver after CBDL and were accompanied by elevated circulating monocyte
      numbers. Splenectomy significantly decreased monocyte accumulation, VEGF-A
      levels, and angiogenesis in CBDL animal lung and improved AaPO2 levels. In
      contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were
      further exacerbated by spleen removal. CONCLUSIONS: Splenic reservoir monocytes
      are a major source for lung monocyte accumulation after CBDL, and spleen removal
      attenuates the development of experimental HPS. Liver monocytes may have
      different origins, and accumulation is exacerbated after depletion of splenic
      reservoir monocytes. Tissue specific monocyte alterations, influenced by the
      spleen reservoir, have a significant impact on pulmonary complications of liver
      disease.

PMID- 27029416
TI  - Antibiotics: Responding to a Global Challenge.
AB  - The miracle of antibiotics is hard to exaggerate. Each day, in every corner of
      the world, antibiotics improve, or could be improving outcomes in the septic
      neonate, the child with pneumonia, the new mother after a complicated delivery,
      the patient undergoing surgery, the nursing home resident with a urinary tract
      infection, the patient being treated of cancer, or the trauma patient on life
      support. The miracle also keeps our animals healthy for effective food
      production. But the miracle of these 'wonder drugs' is under threat and may be
      short lived: antimicrobial resistance is relentlessly increasing, especially for
      Gram negative organisms, prompting the oft expressed concern that we are
      plummeting head-long back into the pre-antibiotics era where clinicians and
      families once again will have to stand by and watch patients and loved ones die
      from once easily-treated infections. [...]. 

PMID- 27029415
TI  - Classification Framework and Chemical Biology of Tetracycline-Structure-Based
      Drugs.
AB  - By studying the literature about tetracyclines (TCs), it becomes clearly evident
      that TCs are very dynamic molecules. In some cases, their structure-activity
      relationship (SAR) are well known, especially against bacteria, while against
      other targets, they are virtually unknown. In other diverse fields of research
      such as neurology, oncology and virology-the utility and activity of the
      tetracyclines are being discovered and are also emerging as new technological
      fronts. The first aim of this paper is to classify the compounds already used in
      therapy and prepare the schematic structure that includes the next generation of
      TCs. The second aim of this work is to introduce a new framework for the
      classification of old and new TCs, using a medicinal chemistry approach to the
      structure of those drugs. A fully documented Structure-Activity-Relationship
      (SAR) is presented with the analysis data of antibacterial and nonantibacterial
      (antifungal, antiviral and anticancer) tetracyclines. The lipophilicity and the
      conformational interchangeability of the functional groups are employed to
      develop the rules for TC biological activity. 

PMID- 27029417
TI  - Gelation Behavior of 5-Chloro-8-hydroxyquinoline, an Antituberculosis Agent in
      Aqueous Alcohol Solutions.
AB  - It was shown that 5-chloro-8-hydroxyquinoline, an antituberculosis agent, gels
      aqueous alcohol solutions efficiently. Thermal stability and gel-to-sol
      transition temperature of 1% gel in CD3OD/D2O (2:1) was studied by 1H-NMR.
      Fibrous structures of four xerogels have been characterized by scanning electron
      microscope. 

PMID- 27029419
TI  - Amorphous Strontium Titanate Film as Gate Dielectric for Higher Performance and
      Low Voltage Operation of Transparent and Flexible Organic Field Effect
      Transistor.
AB  - We report that the pervoskite material, strontium titanate (STO) can be used as a
      gate dielectric layer of flexible and low voltage organic field effect transistor
      (OFET). The crystallinity, dielectric constant, and surface morphology of STO
      films can be controlled by the engineering of the growth condition. Under
      optimized growth condition, amorphous films of STO show a much better gate
      dielectric compared to other gate dielectrics used to date, with very small
      leakage current density for flexible and low voltage (<5 V) OFETs. The amorphous
      STO film decreases the interface trap density at organic/dielectric interface
      substantially. Pentacene transistors with amorphous STO gate dielectric show high
      mobility of 2 cm(2)/(V s), on/off ratio of 10(6), subthreshold swing of 0.3 V/dec
      and low interface trap density. Similarly excellent performance has been obtained
      in copper phthalocyanine (CuPc) based OFETs with on/off ratio ~10(5) and carrier
      mobility ~5.9 * 10(-2) cm(2)/(V s). Moreover, the operating voltage (~5 V) has
      been reduced by more than one order of magnitude. It has been demonstrated that
      the low processing temperature of amorphous STO makes it the most suitable gate
      dielectric for flexible and transparent organic devices to operate under low
      voltage.

PMID- 27029418
TI  - Multidrug Efflux Systems in Helicobacter cinaedi.
AB  - Helicobacter cinaedi causes infections, such as bacteremia, diarrhea and
      cellulitis in mainly immunocompromised patients. This pathogen is often
      problematic to analyze, and insufficient information is available, because it
      grows slowly and poorly in subculture under a microaerobic atmosphere. The first
      choice therapy to eradicate H. cinaedi is antimicrobial chemotherapy; however,
      its use is linked to the development of resistance. Although we need to
      understand the antimicrobial resistance mechanisms of H. cinaedi, unfortunately,
      sufficient genetic tools for H. cinaedi have not yet been developed. In July
      2012, the complete sequence of H. cinaedi strain PAGU 611, isolated from a case
      of human bacteremia, was announced. This strain possesses multidrug efflux
      systems, intrinsic antimicrobial resistance mechanisms and typical mutations in
      gyrA and the 23S rRNA gene, which are involved in acquired resistance to
      fluoroquinolones and macrolides, respectively. Here, we compare the organization
      and properties of the efflux systems of H. cinaedi with the multidrug efflux
      systems identified in other bacteria. 

PMID- 27029420
TI  - Clinical Experience of Transcatheter Closure for Residual Ventricular Septal
      Defect in Pediatric Patients.
AB  - BACKGROUND: Open cardiac surgery has traditionally been the gold standard for
      repair of ventricular septal defect (VSD). The inherent risks and complications
      associated with open surgery and the incidence of postoperative residual VSD are
      significant disadvantages of the open surgical approach. OBJECTIVE: To evaluate
      the methodology and efficacy of transcatheter closure of postoperative residual
      VSD in children. METHODS: Patients with postoperative VSD who underwent
      percutaneous device closure in the period from August 2010 and February 2014 in
      our center were analyzed retrospectively. Twelve children, including 8 males and
      4 females, with mean age of 8.13 +/- 5.39 years (range 0.67-17 years) and mean
      weight of 29.63 +/- 20.86 kg (range 5.5-66 kg) were included in the study.
      RESULTS: Ten cases had residual shunts situated at the margin of the patches
      while the other two had residual shunts because of multiple muscular VSD. The
      mean VSD diameter was 3.84 +/- 1.86 mm (range 2.3-8.7 mm). On cardiac
      catheterization, the reported mean pulmonary circulatory blood volume/systemic
      circulation volume (Qp/Qs) ratio was 1.86 +/- 0.91 (range 1.1-4.25) and the mean
      pulmonary artery pressure was 25.92 +/- 12.42 mm Hg (range 7-52 mm Hg).
      Successful transcatheter closure was obtained in all twelve patients with
      postsurgery residual VSD. Two cases with residual muscular VSD underwent
      retrograde catheterization via the femoral artery while one case with residual
      VSD located at the lower margin of the patch was accessed via the internal
      jugular vein. The mean procedure time was 81.25 +/- 25.86 minutes (range 40-120
      minutes). There was no evidence of residual VSD, and no instances of new-onset
      valvular regurgitation were reported, with the only two exceptions being patients
      who had multiple muscular VSDs where clinically insignificant residual shunts
      were detected. CONCLUSION: Our retrospective study highlights the potential
      safety and therapeutic efficacy of transcatheter approach for closing
      postoperative residual VSD in children. RECOMMENDATIONS: More robust studies with
      longer-term follow-up of outcomes are required to firmly establish the safety
      profile and respective indications for use of various occluder devices for
      treating different categories of residual VSD.

PMID- 27029421
TI  - Immuno-physiological adaptations confer wax moth Galleria mellonella resistance
      to Bacillus thuringiensis.
AB  - Microevolutionary mechanisms of resistance to a bacterial pathogen were explored
      in a population of the Greater wax moth, Galleria mellonella, selected for an 8.8
      fold increased resistance against the entomopathogenic bacterium Bacillus
      thuringiensis (Bt) compared with a non-selected (suspectible) line. Defense
      strategies of the resistant and susceptible insect lines were compared to uncover
      mechanisms underpinning resistance, and the possible cost of those survival
      strategies. In the uninfected state, resistant insects exhibited enhanced basal
      expression of genes related to regeneration and amelioration of Bt toxin activity
      in the midgut. In addition, these insects also exhibited elevated activity of
      genes linked to inflammation/stress management and immune defense in the fat
      body. Following oral infection with Bt, the expression of these genes was further
      elevated in the fat body and midgut of both lines and to a greater extent some of
      them in resistant line than the susceptible line. This gene expression analysis
      reveals a pattern of resistance mechanisms targeted to sites damaged by Bt with
      the insect placing greater emphasis on tissue repair as revealed by elevated
      expression of these genes in both the fat body and midgut epithelium. Unlike the
      susceptible insects, Bt infection significantly reduced the diversity and
      richness (abundance) of the gut microbiota in the resistant insects. These
      observations suggest that the resistant line not only has a more intact midgut
      but is secreting antimicrobial factors into the gut lumen which not only mitigate
      Bt activity but also affects the viability of other gut bacteria. Remarkably the
      resistant line employs multifactorial adaptations for resistance to Bt without
      any detected negative trade off since the insects exhibited higher fecundity.

PMID- 27029422
TI  - Chromo-fluorogenic probes for carbon monoxide detection.
AB  - The sensing of carbon monoxide (CO) using electrochemical cells or semiconducting
      metal oxides has led to inexpensive alarms for the home and workplace. It is now
      recognised that chronic exposure to low levels of CO also poses a significant
      health risk. It is perhaps surprising therefore that the CO is used in cell
      signalling pathways and plays a growing role in therapy. However, the selective
      monitoring of low levels of CO remains challenging, and it is this area that has
      benefited from the development of probes which give a colour or fluorescence
      response. This feature article covers the design of chromo-fluorogenic probes and
      their application to CO sensing in air, solution and in cells. 

PMID- 27029423
TI  - Overweight, resting heart rate, and prediabetes/diabetes: A population-based
      prospective cohort study among Inner Mongolians in China.
AB  - We aimed to investigate the cumulative effect of overweight and resting heart
      rate on prediabetes/diabetes incidence in an 10-year follow-up study in Inner
      Mongolians. Among 1729 participants who were free from prediabetes and diabetes
      at baseline, 503 and 155 subjects developed prediabetes and diabetes,
      respectively. We categorized the participants into 4 subgroups according to
      overweight and resting heart rate status. The multivariate-adjusted OR (95% CI)
      in normal weight with heart rate >=80 bpm, overweight with heart rate <80 bpm,
      and overweight with heart rate >=80 bpm were 1.24 (0.95-1.61), 1.83 (1.29-2.61),
      2.20 (1.41-3.45) for prediabetes and 1.52 (0.97-2.40), 3.64 (2.21-6.01), 4.61
      (2.47-8.61) for diabetes, respectively, compared with normal weight with heart
      rate <80 bpm. The area under ROC curve (AUC) for the prediction of diabetes
      incidence for a model containing overweight and resting heart rate, along with
      conventional factors (AUC = 0.751), was significantly (P = 0.003) larger than the
      one containing only conventional factors (AUC = 0.707). Our study indicated that
      overweight was an independent risk factor of prediabetes and diabetes, and
      overweight with faster resting heart rate might further increase the risk of
      prediabetes and diabetes. 

PMID- 27029424
TI  - Constitutively active PKA regulates neuronal acetylcholine release and
      contractility of guinea pig urinary bladder smooth muscle.
AB  - Autonomic and somatic motor neurons that innervate the urinary bladder and
      urethra control the highly coordinated functions of the lower urinary tract, the
      storage, and the emptying of urine. ACh is the primary excitatory
      neurotransmitter in the bladder. Here, we aimed to determine whether PKA
      regulates neuronal ACh release and related nerve-evoked detrusor smooth muscle
      (DSM) contractions in the guinea pig urinary bladder. Isometric DSM tension
      recordings were used to measure spontaneous phasic and electrical field
      stimulation (EFS)- and carbachol-induced DSM contractions with a combination of
      pharmacological tools. The colorimetric method was used to measure ACh released
      by the parasympathetic nerves in DSM isolated strips. The pharmacological
      inhibition of PKA with H-89 (10 MUM) increased the spontaneous phasic
      contractions, whereas it attenuated the EFS-induced DSM contractions.
      Intriguingly, H-89 (10 MUM) attenuated the (primary) cholinergic component,
      whereas it simultaneously increased the (secondary) purinergic component of the
      nerve-evoked contractions in DSM isolated strips. The acetylcholinesterase
      inhibitor, eserine (10 MUM), increased EFS-induced DSM contractions, and the
      subsequent addition of H-89 attenuated the contractions. H-89 (10 MUM)
      significantly increased DSM phasic contractions induced by the cholinergic
      agonist carbachol. The inhibition of PKA decreased the neuronal release of ACh in
      DSM tissues. This study revealed that PKA-mediated signaling pathways
      differentially regulate nerve-evoked and spontaneous phasic contractions of
      guinea pig DSM. Constitutively active PKA in the bladder nerves controls synaptic
      ACh release, thus regulating the nerve-evoked DSM contractions, whereas PKA in
      DSM cells controls the spontaneous phasic contractility.

PMID- 27029426
TI  - New insights into the molecular regulation of urine concentration.

PMID- 27029427
TI  - Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on
      adenine-induced renal injury.
AB  - The aim of the present study was to reveal the effect of a xanthine
      oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another
      inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used
      human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice,
      and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to
      evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2%
      (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal
      dysfunction was confirmed, and the mice were divided into the following four
      groups: the adenine group was given only the diet containing adenine, and the
      Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets
      containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to
      adenine for another 2 wk. After withdrawal of the adenine diet, each medication
      was continued for 2 wk. Serum creatinine levels, the degree of macrophage
      infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t
      isoprostane levels, and renal XOR activity were significantly attenuated in the
      kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group.
      Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the
      Top-H group were significantly lower than those in the Feb group. Urinary
      excretion of L-FABP in both the Top-H and Top-L groups was significantly lower
      than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in
      an adenine-induced renal injury model.

PMID- 27029429
TI  - Is NaHCO3 an antiaging elixir?

PMID- 27029428
TI  - Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of
      chronic kidney disease.
AB  - Thermal therapy has become a nonpharmacological therapy in clinical settings,
      especially for cardiovascular diseases. However, the practical role of thermal
      therapy on chronic kidney disease remains elusive. We performed the present study
      to investigate whether a modified thermal protocol, repeated mild thermal
      stimulation (MTS), could affect renal damages in chronic kidney disease using a
      mouse renal ablation model. Mice were subjected to MTS or room temperature (RT)
      treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation
      (Sh). We revealed that MTS alleviated renal impairment as indicated by serum
      creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed
      attenuated tubular histological changes and reduced urinary neutrophil gelatinase
      associated lipocalin excretion approximately by half compared with the Nx + RT
      group. Increased apoptotic signaling, such as TUNEL-positive cell count and
      cleavage of caspase 3, as well as enhanced oxidative stress were significantly
      reduced in the Nx + MTS group compared with the Nx + RT group. These changes were
      accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock
      protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx
      kidneys rather than in Sh kidneys. MTS also tended to increase the
      phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the
      activation of heat shock protein 27. Taken together, these results suggest that
      modified MTS can protect against renal injury in a rodent model of chronic kidney
      disease.

PMID- 27029425
TI  - Calcium-permeable ion channels in the kidney.
AB  - Calcium ions (Ca(2+)) are crucial for a variety of cellular functions. The
      extracellular and intracellular Ca(2+) concentrations are thus tightly regulated
      to maintain Ca(2+) homeostasis. The kidney, one of the major organs of the
      excretory system, regulates Ca(2+) homeostasis by filtration and reabsorption.
      Approximately 60% of the Ca(2+) in plasma is filtered, and 99% of that is
      reabsorbed by the kidney tubules. Ca(2+) is also a critical signaling molecule in
      kidney development, in all kidney cellular functions, and in the emergence of
      kidney diseases. Recently, studies using genetic and molecular biological
      approaches have identified several Ca(2+)-permeable ion channel families as
      important regulators of Ca(2+) homeostasis in kidney. These ion channel families
      include transient receptor potential channels (TRP), voltage-gated calcium
      channels, and others. In this review, we provide a brief and systematic summary
      of the expression, function, and pathological contribution for each of these
      Ca(2+)-permeable ion channels. Moreover, we discuss their potential as future
      therapeutic targets.

PMID- 27029430
TI  - Role of O-linked N-acetylglucosamine modification in diabetic nephropathy.
AB  - Increased O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation) is a
      known contributor to diabetes; however, its relevance in diabetic nephropathy
      (DN) is poorly elucidated. Here, we studied the process and enzymes of O
      GlcNAcylation with a special emphasis on Akt-endothelial nitric oxide synthase
      (eNOS) and heat shock protein (HSP)72 signaling. Since tubular injury is the
      prominent site of DN, the effect of hyperglycemia was first measured in proximal
      tubular (HK2) cells cultured in high glucose. In vivo O-GlcNAcylation and protein
      levels of O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), phosphorylated
      (p)Akt/Akt, peNOS/eNOS, and HSP72 were assessed in the kidney cortex of
      streptozotocin-induced diabetic rats. The effects of various renin-angiotensin
      aldosterone system (RAAS) inhibitors were also evaluated. In proximal tubular
      cells, hyperglycemia-induced OGT expression led to increased O-GlcNAcylation,
      which was followed by a compensatory increase of OGA. In parallel, peNOS and pAkt
      levels decreased, whereas HSP72 increased. In diabetic rats, elevated O
      GlcNAcylation was accompanied by decreased OGT and OGA. RAAS inhibitors
      ameliorated diabetes-induced kidney damage and prevented the elevation of O
      GlcNAcylation and the decrement of pAkt, peNOS, and HSP72. In conclusion,
      hyperglycemia-induced elevation of O-GlcNAcylation contributes to the progression
      of DN via inhibition of Akt/eNOS phosphorylation and HSP72 induction. RAAS
      blockers successfully inhibit this process, suggesting a novel pathomechanism of
      their renoprotective action in the treatment of DN.

PMID- 27029432
TI  - Effects of sodium arsenate and arsenite on male reproductive functions in Wistar
      rats.
AB  - Arsenic (As), in the form of trivalent arsenite or pentavalent arsenate, is a
      ubiquitous toxic compound naturally occurring in the environment. This study
      aimed to evaluate the impact of two different forms of inorganic As on
      reproductive parameters following oral exposure. Adult Wistar male rats were
      exposed to sodium arsenite or arsenate at concentrations of 0.01 mg/L or 10 mg/L
      for 56 d in drinking water. Sodium arsenite at both concentrations and sodium
      arsenate at 10 mg/L produced reduction in daily sperm production, in number of
      spermatids in the testis, and in sperm in the epididymal caput/corpus regions.
      Changes in epididymal morphometry were variable and region specific. Total and
      progressive sperm motility and sperm morphology did not differ markedly between
      controls and animals exposed to As. The body and reproductive organs weights, as
      well as testosterone concentration, remained unchanged among all groups. In
      conclusion, As exposure in drinking water over 56 d produced damage in male
      reproductive functions in adult rats, suggesting that fertility problems might
      occur. Therefore, additional studies need to be undertaken to investigate
      potential mechanisms underlying sodium arsenite- and arsenate-induced
      disturbances in fertility and reproductive performance. 

PMID- 27029431
TI  - A multiplexed analysis approach identifies new association of inflammatory
      proteins in patients with overactive bladder.
AB  - Overactive bladder (OAB) is a common debilitating bladder condition with unknown
      etiology and limited diagnostic modalities. Here, we explored a novel high
      throughput and unbiased multiplex approach with cellular and molecular components
      in a well-characterized patient cohort to identify biomarkers that could be
      reliably used to distinguish OAB from controls or provide insights into
      underlying etiology. As a secondary analysis, we determined whether this method
      could discriminate between OAB and other chronic bladder conditions. We analyzed
      plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB,
      interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections
      (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and
      vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary
      cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and
      multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI).
      Multivariate logistic regression models were fit for each MSD analyte on 1) OAB
      patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients.
      Age, race, and sex were included as independent variables in all multivariate
      analysis. Receiver operating characteristic (ROC) curves were generated to
      determine the diagnostic potential of a given analyte. Our findings demonstrate
      that five analytes, i.e., interleukin 4, TNF-alpha, macrophage inflammatory
      protein-1beta, serum amyloid A, and Tie2 can reliably differentiate OAB relative
      to controls and can be used to distinguish OAB from the other conditions.
      Together, our pilot study suggests a molecular imbalance in inflammatory proteins
      may contribute to OAB pathogenesis.

PMID- 27029433
TI  - Giant and broadband circular asymmetric transmission based on two cascading
      polarization conversion cavities.
AB  - In this paper, a three-layered sandwiched metamaterial is proposed to achieve
      giant and broadband asymmetric transmission of circularly polarized waves at the
      near-infrared communication band. The metamaterial consists of two layers of
      identical 45 degrees  tilted chiral S-shaped metasurfaces sandwiched with a
      subwavelength metallic grating. Based on the delicate combination of broadband
      polarization conversion and a cavity-enhanced effect, the asymmetric parameter
      can reach a maximum value of 0.87 and over 0.6 in a wide range from 1.2 to 2.0
      MUm, which has not been found in previous reports. Furthermore, a perfect
      robustness to misalignments is obtained as the effect originated from function
      independent cascading cavities, which effectively reduce the requirement of
      alignment precision in layer-by-layer photolithography processes. The proposed
      nanostructure has a great potential to be used as a circular polarization rotator
      or diode-like device in optical communication systems. 

PMID- 27029434
TI  - Corrigendum: Modulation of expression of genes involved in glycosaminoglycan
      metabolism and lysosome biogenesis by flavonoids.

PMID- 27029435
TI  - HLA-C*06:04:02 a novel HLA-C allele isolated from donors of Southern African
      descent.
AB  - HLA-C*06:04:02 allele differs from HLA-C*06:02:01:01 with two nucleotide
      substitutions in exon 3 and 3' untranslated region (UTR_. 

PMID- 27029436
TI  - Biochemistry-directed hollow porous microspheres: bottom-up self-assembled
      polyanion-based cathodes for sodium ion batteries.
AB  - Biochemistry-directed synthesis of functional nanomaterials has attracted great
      interest in energy storage, catalysis and other applications. The unique ability
      of biological systems to guide molecule self-assembling facilitates the
      construction of distinctive architectures with desirable physicochemical
      characteristics. Herein, we report a biochemistry-directed "bottom-up" approach
      to construct hollow porous microspheres of polyanion materials for sodium ion
      batteries. Two kinds of polyanions, i.e. Na3V2(PO4)3 and Na3.12Fe2.44(P2O7)2, are
      employed as cases in this study. The microalgae cell realizes the formation of a
      spherical "bottom" bio-precursor. Its tiny core is subjected to destruction and
      its tough shell tends to carbonize upon calcination, resulting in the hollow
      porous microspheres for the "top" product. The nanoscale crystals of the
      polyanion materials are tightly enwrapped by the highly-conductive framework in
      the hollow microsphere, resulting in the hierarchical nano-microstructure. The
      whole formation process is disclosed as a "bottom-up" mechanism. Moreover, the
      biochemistry-directed self-assembly process is confirmed to play a crucial role
      in the construction of the final architecture. Taking advantage of the well
      defined hollow-microsphere architecture, the abundant interior voids and the
      highly-conductive framework, polyanion materials show favourable sodium
      intercalation kinetics. Both materials are capable of high-rate long-term
      cycling. After five hundred cycles at 20 C and 10 C, Na3V2(PO4)3 and
      Na(3.12)Fe2.44(P2O7)2 retain 96.2% and 93.1% of the initial capacity,
      respectively. Therefore, the biochemistry-directed technique provides a low-cost,
      highly-efficient and widely applicable strategy to produce high-performance
      polyanion-based cathodes for sodium ion batteries.

PMID- 27029437
TI  - Magnetic response of gelatin ferrogels across the sol-gel transition: the
      influence of high energy crosslinking on thermal stability.
AB  - As emerging responsive materials, ferrogels have demonstrated significant
      potential for applications in areas of engineering to regenerative medicine.
      Promising techniques to study the behavior of magnetic nanoparticles (MNPs) in
      such matrices include magnetic particle spectroscopy (MPS) and magnetorelaxometry
      (MRX). This work investigated the magnetic response of gelatin-based ferrogels
      with increasing temperatures, before and after high energy crosslinking. The
      particle response was characterized by the nonlinear magnetization using MPS and
      quasistatic magnetization measurements as well as MRX to discriminate between
      Neel and Brownian relaxation mechanisms. The effective magnetic response of MNPs
      in gelatin was suppressed, indicating that the magnetization of the ferrogels was
      strongly influenced by competing dipole-dipole interactions. Significant changes
      in the magnetic behavior were observed across the gelatin sol-gel transition, as
      influenced by the matrix viscosity. These relaxation processes were modeled by
      Fourier transformation of the Langevin function, combined with a Debye term for
      the nonlinear magnetic response, for single core MNPs embedded in matrices of
      changing viscosities. Using high energy electron irradiation as a crosslinking
      method, modified ferrogels exhibited thermal stability on a range of timescales.
      However, MRX relaxation times revealed a slight softening around the gelatin sol
      gel transition felt by the smallest particles, demonstrating a high sensitivity
      to observe local changes in the viscoelasticity. Overall, MPS and MRX functioned
      as non-contact methods to observe changes in the nanorheology around the native
      sol-gel transition and in crosslinked ferrogels, as well as provided an
      understanding of how MNPs were integrated into and influenced by the surrounding
      matrix.

PMID- 27029440
TI  - [A monogenic model of schizophrenia: a shift in paradigms].
AB  - Advanced genome technologies, including genome-wide association studies, next
      generation sequencing analysis, whole exome sequencing, encourage the development
      of theoretical insights on the role of genetic factors in schizophrenia. In this
      context, the author considers a monogenic model of schizophrenia and its
      evolution. 

PMID- 27029438
TI  - The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker
      of Quantitative State Changes in Glucose Metabolism.
AB  - The evolution of functional magnetic resonance imaging to resting state (R-fMRI)
      allows measurement of changes in brain networks attributed to state changes, such
      as in neuropsychiatric diseases versus healthy controls. Since these networks are
      observed by comparing normalized R-fMRI signals, it is difficult to determine the
      metabolic basis of such group differences. To investigate the metabolic basis of
      R-fMRI network differences within a normal range, eyes open versus eyes closed in
      healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro
      deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was
      observed in the eyes open state. Variance-based metrics calculated from R-fMRI
      did not match the baseline shift in FDG. Functional connectivity density (FCD)
      based metrics showed a shift similar to the baseline shift of FDG, however, this
      was lost if R-fMRI "nuisance signals" were regressed before FCD calculation.
      Average correlation with the mean R-fMRI signal across the whole brain, generally
      regarded as a "nuisance signal," also showed a shift similar to the baseline of
      FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation
      may reflect changes in baseline brain metabolism. Conversely, variance-based
      metrics may remain similar between states due to inherent region-to-region
      differences overwhelming the differences between normal physiological states. As
      most previous studies have excluded the spatial means of R-fMRI metrics from
      their analysis, this work presents the first evidence of a potential R-fMRI
      biomarker for baseline shifts in quantifiable metabolism between brain states.

PMID- 27029441
TI  - [Enterovirus infections and meningitis in children].
AB  - OBJECTIVE: To compare clinical characteristics in children with enterovirus
      infections (EVI) and meningitis with detailed characteristics of the changes in
      the content of cerebrospinal fluid (CSF) confirmed in the laboratory. MATERIAL
      AND METHODS: The results of examinations of 97 children, aged from 2.5 to 15
      years, 3 adolescents and 1 adult female patient with EVI were analyzed.
      Enterovirus RNA isolation and detection in feces and CSF was performed using PCR.
      RESULTS AND CONCLUSION: Enterovirus RNA in CSF was detected in 44 children,
      including 3 patients with cytosis (5-7-19 cells in 3 mm3). The frequency and
      severity of symptoms in 42 patients with EVI and meningitis, 14 children with EVI
      without meningitis and 8 patients with ICD-10 "Meningitis unspecified" are
      presented. The initial CSF pleocytosis in 1-3 day (4-5 day for two-wave course)
      in EVI and meningitis was <100 in 4, from 100 to 1000 in 33, >1000 (max 3036)
      cells in 3 mm3 in 5 patients, including 15 with the predominance of neutrophils
      (from 77 to 97% in cytosis 114-2300 cells in 3 mm(3)). In the peripheral blood,
      leukocytosis 10.9-13.8*10(9)/l was noted in 12 children and leukocytosis 14.4
      18.7*10(9)/l with the "left shift" in 7. Most of the children (n=37) with EVI and
      meningitis were discharged from the hospital within 10-17 days. The authors
      suggest the importance of including the variety of clinical presentations of EVI
      in the additional item "B10 Enterovirus infections" in upcoming ICD-11.

PMID- 27029442
TI  - [The dynamics of psychopathological symptoms of ultra high risk for psychosis in
      young patients with non-psychotic mental disorders].
AB  - OBJECTIVE: Based on the results of 5-year follow-up study, to describe the
      dynamics of psychopathological symptoms in young patients with non-psychotic
      forms of mental diseases met the criteria of ultra-high risk for schizophrenia
      who received preventive psychopharmacotherapy. MATERIAL AND METHODS: The study
      included 32 young men, aged 16--25 years, presented with the symptoms of ultra
      high risk of schizophrenia during the first hospitalization in 2009--2011. Follow
      up was carried out in 2014--2015 (mean follow-up 5.79+/-0.36 years). According to
      ICD-10, patients were stratified into 3 groups: mood disorders, personality
      disorders and schizotypal disorders. RESULTS AND CONCLUSION: According to the
      characteristics of subsequent development of these disorders, four types were
      singled out: mechanisms of the development of acute sensitive delusions (I),
      interpretative delusions (II), catatonic disorganization (III) and cognitive
      disorders pathognomonic for schizophrenia spectrum disorders (IV). Correlations
      between these types and nosologic disorders and their different reversibility
      under treatment were found. These types can be considered as predictors of
      outcome over the follow-up period.

PMID- 27029443
TI  - [Treatment tactics for patients with combined atherosclerotic lesions of
      brachiocephalic and coronary arteries].
AB  - OBJECTIVE: To evaluate the tactics of surgical treatment of patients with
      coronary heart disease and atherosclerotic lesions of cerebral vessels in
      dependence of risk stratification of heart and brain complications. MATERIAL AND
      METHODS: One hundred and fifty-six patients were examined. Cerebral and coronary
      blood flow and functional state of the brain and heart were studied. According to
      treatment characteristics, 3 groups were singled out: patients of the 1(st) group
      underwent simultaneous surgery of coronary and brachiocephalic arteries, patients
      of the 2(nd) group were first operated for brachiocephalic arteries, in the 3(rd)
      group, bypass graft was performed in the first stage. RESULTS AND CONCLUSION: A
      role of coronary and brachiocephalic arteries, functional state of the myocardium
      and brain in the postoperative risk was established. The authors suggest the
      algorithm for choosing the order of priority of surgical interventions on
      coronary and brachiocephalic arteries.

PMID- 27029444
TI  - [Efficacy and safety of transcranial magnetic stimulation in the treatment of
      rare forms of muscular dystonia].
AB  - OBJECTIVE: To evaluate the efficacy and safety of repetitive transcranial
      magnetic stimulation (rTMS) for the treatment of patients with dystonia. MATERIAL
      AND METHODS: Authors treated 66 patients with segmental and generalized forms of
      dystonia, writer's cramp and oromandibular dystonia. The degree of dystonia
      severity was assessed using the Burke--Fahn--Marsden scale. RESULTS AND
      CONCLUSION: rTMS treatment of the motor cortex region decreased dystonic
      hyperkinesis severity. There was a significant decrease in scores on the Burke-
      Fahn--Marsden scale (p<0.05). This method was well-tolerated. No side-effects
      were observed, with the exception of one patient, who wished to discontinue
      treatment because of the twitching of facial muscles during rTMS. The results of
      the study allow to recommend wider adoption of this method in complex treatment
      and rehabilitation of patients with rare forms of dystonia.

PMID- 27029445
TI  - [The efficacy of pharmacological preconditioning in carotid endarterectomy].
AB  - OBJECTIVE: To assess the efficacy of pharmacological preconditioning with
      actovegin in carotid endarterectomy. MATERIAL AND METHODS: The study was based on
      the results of surgical treatment of 80 patients with hemodynamically significant
      uni- and bilateral lesions of carotid arteries. Half of the patients was operated
      immediately and others after pharmacological preconditioning with actovegin in
      dose of 1200 mg/daily during 1,5 months. RESULTS: Pharmacological preconditioning
      with actovegin increased the cerebral perfusion determined with one-photon
      emission computed tomography that improved significantly results of the surgery.
      There were significant changes in patient's state 7 days and 6 months after
      surgery. The improvement was correlated with the less number of asymptotic post
      surgery ischemic strokes in different brain areas. CONCLUSION: A positive role of
      pharmacological preconditioning with actovegin in surgical treatment of carotid
      artery stenosis has been demonstrated.

PMID- 27029446
TI  - [Optimization of hypolipidemic therapy in patients with ischemic stroke and
      diabetes mellitus].
AB  - OBJECTIVES: Evaluation of effectiveness of Mexidol in optimization of
      hypolipidemic therapy in ischemic stroke and diabetes mellitus patients. MATERIAL
      AND METHODS: Authors analyzed the indicators of lipid status: total cholesterol,
      low-density lipoproteins, high density lipoproteins, triglycerides and
      concentration of platelet factor-4, beta-tromboglobulin, von Willebrand factor in
      68 patients with acute ischemic stroke and diabetes mellitus. Authors investigate
      the dynamics of these parameters (1(st), 21(st), 3-d and 6(th) month after onset
      stroke) depending on timing and dose of Mexidol. RESULTS: Long time therapy of
      Mexidol may optimize of hypolipidemic therapy in ischemic stroke and diabetes
      mellitus patients.

PMID- 27029447
TI  - [The association between the 5-HTTLPR polymorphism of the serotonin transporter
      gene and the efficacy and tolerability of selective serotonin reuptake
      inhibitors].
AB  - OBJECTIVE: To search for the association between the 5-HTTLPR polymorphism of the
      serotonin transporter gene and the efficacy and tolerability of selective
      serotonin reuptake inhibitors (SSRIs). MATERIAL AND METHODS: The complex
      clinical/psychopathological and genetic study of 38 patients with depression
      treated with SSRIs was carried out. RESULTS AND CONCLUSION: The 5-HTTLPR
      polymorphism was associated with the rate of achievement of remission and
      tolerability of treatment: carriers of the SS genotype achieved remission less
      frequently and more frequently experienced side-effects.

PMID- 27029448
TI  - [Clinical experience of the use of memantal in patients with moderate and severe
      Alzheimer's disease].
AB  - OBJECTIVE: To assess the efficacy and safety of memantal, a generic formulation
      of memantine, in patients with moderate and severe dementia due to Alzheimer's
      disease (AD). MATERIAL AND METHODS: Thirty patients with moderate and severe AD,
      aged from 55 to 84 years, were examined. Memantal was used in the dose of 20 mg
      per day after the titration period. Duration of treatment was 3 months. RESULTS:
      To the end of the study, there was a moderate positive effect as assessed by the
      CGI. During the treatment, cognitive functions and different forms of daily
      activity have improved. Significant positive changes in behavioral symptoms of
      dementia were noted. No adverse effects were observed during the treatment.
      CONCLUSION: The results of the analysis revealed the clinical efficacy and safety
      of memantal in treatment of AD.

PMID- 27029449
TI  - [Tension type headache: GABA-ergic drug anvifen efficacy].
AB  - OBJECTIVE: To assess the efficacy of aminophenylbutyric acid (anvifen), a
      synthetic GABA-receptor agonist, in the treatment of adult patients with tension
      type headache (TTH). MATERIAL AND METHODS: Eighty-seven patients with episodic
      TTH (ETTH) and 30 patients with chronic TTH (CTTH) were examined. The area under
      the headache curve, sleep quality, the Hospital Anxiety and Depression Scale
      (HADS) scores and stress resistance measured by an original questionnaire were
      evaluated. RESULTS: Anvifen in dose of 250 mg TID during 3 weeks had a positive
      effect on all parameters studied, excluding the area under the headache curve in
      CTTH. Similar results were demonstrated after the subsequent course of treatment
      for 3 weeks. CONCLUSION: Anvifen was highly effective in ETTH but less effective
      in CTTH. A combination of anvifen with antidepressants can be recommended for
      patients with CTTH.

PMID- 27029450
TI  - [Diagnosis and treatment of psychogenic dizziness in patients with arterial
      hypertension].
AB  - OBJECTIVE: To analyze the prevalence, methods of diagnosis and treatment of
      psychogenic dizziness in patients with arterial hypertension and evaluate the
      efficacy of treatment with noophen and betahistin. MATERIAL AND METHODS: Fifty
      eight patients were studied. Patients of the main group received noophen and
      patients of the comparison group were treated with betahistin. Treatment efficacy
      was assessed on days 1 and 60 by the scores on VAS, HARS, MFI-20 scales. RESULTS
      AND CONCLUSION: The prevalence of psychogenic dizziness in patients with arterial
      hypertension was 47%. Noophen in dose 500 mg/day significantly (p<0.001) reduced
      the severity of dizziness, anxiety, asthenia, and headache compared to baseline
      and to the efficacy of betahistin as well. The drug showed good tolerability.

PMID- 27029451
TI  - [The efficacy of intravenous lacosamide in psychiatric hospital].
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of intravenous lacosamide
      (vimpat) in inpatients with frequent partial-onset seizures and affective and
      cognitive disorders. MATERIAL AND METHODS: Fifteen patients were enrolled
      including 14 patients diagnosed with "organic personality disorder associated
      with epilepsy" (cryptogenic or symptomatic epilepsy with frequent partial-onset
      and/or secondary-generalized seizures (serial seizures in some cases) and 1
      patient with a preliminary diagnosis of "organic schizophrenia-like disorder",
      which was changed for "organic personality disorder associated with epilepsy"
      after examination. Patients were treated with 2--3 antiepileptic drugs (AEDs),
      but no one of them received earlier lacosamide. Lacosamide was used intravenously
      in drops in the dose of 200 or 400 mg daily during 5 days. RESULTS AND
      CONCLUSION: In 4 patients with marked personality disorders, the frequency of
      seizures decreased by 75%, no seizures were noted after 2--3 days of treatment in
      11 patients. A positive effect of lacosamide on the affective sphere and quality
      of-life was observed in 11 (73.4%) patients with epilepsy. Mild and moderate
      adverse effects were found only in 2 patients. It has been concluded that
      lacosamide demonstrates the high efficacy in patients with frequent drug
      resistant seizures.

PMID- 27029452
TI  - [Assessing the impact of citicoline on the efficiency of rehabilitation measures
      in patients with ischemic stroke].
AB  - OBJECTIVE: To evaluate the effect of citicoline on the efficacy of rehabilitation
      measures in patients with ischemic stroke (IS). MATERIAL AND METHODS: Sixty
      patients were examined in the acute period of hemispheric IS. All patients
      underwent routine comprehensive treatment. The study group included 30 patients
      who received citicoline within the first 24 hours after IS onset. The control
      group consisted of 30 patients who were not treated with citicoline. The
      examination of patients included the assessment of neurological deficit,
      cognitive functions, P300 evoked potentials, head single photon emission computed
      tomography. RESULTS: Six months after the onset of disease, there was a
      significant improvement in cognitive functions as assessed with the MMSE and MoSa
      scale, and P300 latency in the main group. There was a trend towards the
      improvement in the activities of daily living (Barthel index) in patients of the
      main group compared to the control group. SPECT results showed the improvement in
      cerebral perfusion in an affected hemisphere: in Broca's area, the rear sections
      of the upper and middle frontal gyrus, the parietal lobe (p <0,05). CONCLUSION:
      Citicoline significantly improves cognitive function, which in turn has a
      positive effect on the efficacy of remediation and indirectly improves cerebral
      perfusion in patients with hemispheric IS.

PMID- 27029453
TI  - [The modified method registration of kinesthetic evoked potentials and its
      application for research of proprioceptive sensitivity disorders at spondylogenic
      cervical myelopathy].
AB  - OBJECTIVE: To analyze the efficacy of modified (passive radiocarpal articulation
      flexion/extension) and "standard" (passive radiocarpal articulation flexion)
      methods of kinesthetic evoked potentials for proprioceptive sensitivity
      assessment in healthy subjects and patients with spondylotic cervical myelopathy.
      MATERIAL AND METHODS: The study included 14 healthy subjects (4 women and 10 men,
      mean age 54.1+/-10.5 years) and 8 patients (2 women and 6 men, mean age 55.8+/
      10.9 years) with spondylotic cervical myelopathy. Muscle-joint sensation was
      examined during the clinical study. A modified method of kinesthetic evoked
      potentials was developed. This method differed from the "standard" one by the
      organization of a cycle including several passive movements,where each new
      movement differed from the preceding one by the direction. RESULTS AND
      SONCLUSION: The modified method of kinesthetic evoked potentials ensures more
      reliable kinesthetic sensitivity assessment due to movement variability.
      Asignificant increaseof the latent periods of the early components of the
      response was found in patients compared to healthy subjects. The modified method
      of kinesthetic evoked potentials can be used for objective diagnosis of
      proprioceptive sensitivity disorders in patients with spondylotic cervical
      myelopathy.

PMID- 27029454
TI  - [The relationship between quantitative clinical and EEG parameters in the
      treatment of delusional conditions in patients with attack-like schizophrenia].
AB  - OBJECTIVE: To study neurophysiologic correlates of the severity of clinical
      conditions and to search for possible predictors of therapeutic response in
      attack-like schizophrenic patients with delusional disorders. MATERIAL AND
      METHODS: During the treatment of 40 attack-like schizophrenic patients (all
      females, right-handed, aged 20--50 years old) with delusional disorders, clinical
      symptoms were quantitatively assessed using PANSS. Resting EEG was recorded with
      the consequent spectral-coherent analysis. Correlation analysis was performed at
      the beginning of treatment and at the stage of the development of remission.
      RESULTS: Significant (p<0.05) correlations between some initial (before
      treatment) resting EEG parameters and PANSS scores before treatment and at the
      stage of remission were revealed. The reduction in psychopathologic symptoms
      after treatment course was associated with the decrease in alpha-3 spectral power
      in occipital zones and increase of theta-1 and theta-2 spectral power in frontal
      central regions. Besides, the number of statistically significant intra
      hemispheric and inter-hemispheric links was increased in theta-1 and theta-2
      frequency bands in frontal and central regions compared to initial levels.
      CONCLUSION: These EEG changes reflected the facilitation of cortical inhibitory
      processes as well as recovery of impaired intra-cortical links i.e. the
      normalization of the brain integrative activity.

PMID- 27029455
TI  - [The possibility of using immunological parameters for the evaluation of the
      clinical state of patients with childhood-onset schizophrenia].
AB  - OBJECTIVE: To compare clinical and immunological parameters in children with
      schizophrenia and to analyze the possibility of using them in the assessment of
      the pathological process activity. MATERIAL AND METHODS: We examined 62 patients,
      39 boys and 23 girls, aged from 4 to 17 years, with childhood-onset
      schizophrenia. Mental state of the patients was assessed using a
      psychopathological method and with PANSS and CGI scales. The activity of
      leukocyte elastase (LE) and alpha(1)-proteinase inhibitor (alpha1-PI) was
      measured by spectrophotometric method. ELISA was used to determine the level of
      autoantibodies to neuroantigenes to S-100B and basic myelin protein. RESULTS AND
      CONCLUSION: The activation of innate immunity assessed by the activity of LE and
      alpha1-PI and adaptive immunity (levels of autoantibodies to neuroantigenes to S
      100B and basic myelin protein) was identified. Significant correlations of the
      level of immune system activation with the severity of patient's state on SGI-S
      (r=0.64, p=0.000001) as well as scores on the PANSS negative symptom subscale
      (r=0.34, p=0.0077) were found. The results suggest the possibility of using these
      immunological parameters for the objectification of clinical state of children
      with schizophrenia.

PMID- 27029456
TI  - [Modelling the dynamics of suicides in the population of the Russian Federation
      for the period 1992-2012].
AB  - OBJECTIVE: Evaluation of the dynamics of suicides depending on the changes in
      medical-demographic and socio-economic factors in the Russian population in the
      period 1992--2012. MATERIAL AND METHODS: The research material was the data of
      the official medical statistics on the groups of people with mental disorders, as
      well as the data on the socio-economic situation of the Russian population during
      this period. To assess the significance of the association between suicide and
      these factors, correlation and regression analysis was used. RESULTS: The
      regression model explained 95.9% of the variance in the suicide index by two
      indicators: 1) life expectancy and 2) morbidity of psychotic disorders for the
      population of Russia during this period. The interpretation of the integral
      indicators used in the model, and the dynamics of suicides in the Russian
      population according to socio-economic changes in the country in 1992--2012 are
      presented. CONCLUSION: The model can be used as a tool for operational
      forecasting and monitoring of suicidal patients by government agencies and
      medical and social services.

PMID- 27029457
TI  - [On definitions and axioms in psychiatry].

PMID- 27029458
TI  - Sex reversal assessments reveal different vulnerability to endocrine disruption
      between deeply diverged anuran lineages.
AB  - Multiple anthropogenic stressors cause worldwide amphibian declines. Among
      several poorly investigated causes is global pollution of aquatic ecosystems with
      endocrine disrupting compounds (EDCs). These substances interfere with the
      endocrine system and can affect the sexual development of vertebrates including
      amphibians. We test the susceptibility to an environmentally relevant
      contraceptive, the artificial estrogen 17alpha-ethinylestradiol (EE2),
      simultaneously in three deeply divergent systematic anuran families, a model
      species, Xenopus laevis (Pipidae), and two non-models, Hyla arborea (Hylidae) and
      Bufo viridis (Bufonidae). Our new approach combines synchronized tadpole exposure
      to three EE2-concentrations (50, 500, 5,000 ng/L) in a flow-through-system and
      pioneers genetic and histological sexing of metamorphs in non-model anurans for
      EDC-studies. This novel methodology reveals striking quantitative differences in
      genetic-male-to-phenotypic-female sex reversal in non-model vs. model species.
      Our findings qualify molecular sexing in EDC-analyses as requirement to identify
      sex reversals and state-of-the-art approaches as mandatory to detect species
      specific vulnerabilities to EDCs in amphibians. 

PMID- 27029459
TI  - A randomized phase I trial evaluating the effects of inhaled 50-50% N2 O-O2 on
      remifentanil-induced hyperalgesia and allodynia in human volunteers.
AB  - BACKGROUND: Opioids are known to relieve pain, and also aggravate pre-existing
      hyperalgesia. In animal studies, the N-methyl-d-aspartate-receptor antagonist
      nitrous oxide (N2 O) was able to prevent hyperalgesia. The present study
      evaluated the effect of N2 O on hyperalgesia after remifentanil infusion in
      healthy volunteers. METHODS: Twenty-one healthy volunteers were enrolled in this
      placebo-controlled cross-over study. Transcutaneous electrical stimulation at
      high current densities induced spontaneous acute pain and stable areas of
      hyperalgesia. Each volunteer underwent the following four sessions: (1) 50-50% N2
      -O2 and i.v. saline; (2) 50-50% N2 -O2 and i.v. remifentanil 0.1 MUg/kg/min; (3)
      50-50% N2 O-O2 and i.v. saline; (4) 50-50% N2 O-O2 and i.v. remifentanil 0.1
      MUg/kg/min. Inhaled gas mixtures lasted for 60 min, i.v. drug administration for
      30 min. Visual analogue scale pain intensity, areas of pinprick hyperalgesia and
      touch-evoked allodynia were assessed repeatedly for 160 min. RESULTS: Data of 19
      volunteers were analysed. There were significant time and treatment effects
      regarding areas of hyperalgesia and allodynia (p < 0.02). The area of
      hyperalgesia was significantly reduced in the N2 O + remifentanil session
      compared to the remifentanil session (35.88 +/- 22.37 vs. 43.55 +/- 18.48 cm(2) ,
      p = 0.004). The area of allodynia was significantly reduced in the N2 O +
      remifentanil session compared to the remifentanil session (29.95 +/- 16.15 vs.
      34.80 +/- 15.35 cm(2) , p = 0.008). The pain intensity was significantly reduced
      in the N2 O + remifentanil session compared to the remifentanil session (37.96 +/
      12.78 vs. 42.15 +/- 13.34 mm, p < 0.0001). CONCLUSIONS: Nitrous oxide
      significantly reduced hyperalgesia, allodynia and pain intensity aggravated after
      remifentanil administration in a human volunteer model. WHAT DOES THIS STUDY
      ADD?: This study brings the evidence that N2 O reduces the remifentanil
      aggravated secondary hyperalgesia in human volunteers exposed to a well-known
      model of electrical pain. N2 O was able to oppose the hyperalgesia, the allodynia
      and the pain intensity consecutive to remifentanil use in this specific pain
      model.

PMID- 27029460
TI  - Explaining age differences in women's emotional well-being: The role of
      subjective experiences of aging.
AB  - Our study examines explanations for the "paradox" of older women's better
      emotional well-being compared with younger women. We consider the role of
      subjective experiences of aging in a society that devalues older women. Using a
      sample of women (n = 872) from the National Survey of Midlife Development in the
      United States (1995-1996 and 2004-2006), we examine the role of five components
      of the subjective experience of aging in explaining older women's better
      emotional well-being compared with younger women: age identity, conceptions of
      the timing of middle age, aging attitudes, aging anxieties, and self-assessed
      physiological changes. We find that, compared with women 50-54 years old, those
      35-39 years old report lower positive affect, and those 25-49 report higher
      negative affect. These patterns are partially explained by younger women's
      greater anxiety about declines in health and attractiveness and older women's
      more youthful identities. Our study underscores the value of considering the
      implications of our ageist and sexist society for women's emotional well-being
      across adulthood. 

PMID- 27029461
TI  - Rationally reduced libraries for combinatorial pathway optimization minimizing
      experimental effort.
AB  - Rational flux design in metabolic engineering approaches remains difficult since
      important pathway information is frequently not available. Therefore empirical
      methods are applied that randomly change absolute and relative pathway enzyme
      levels and subsequently screen for variants with improved performance. However,
      screening is often limited on the analytical side, generating a strong incentive
      to construct small but smart libraries. Here we introduce RedLibs (Reduced
      Libraries), an algorithm that allows for the rational design of smart
      combinatorial libraries for pathway optimization thereby minimizing the use of
      experimental resources. We demonstrate the utility of RedLibs for the design of
      ribosome-binding site libraries by in silico and in vivo screening with
      fluorescent proteins and perform a simple two-step optimization of the product
      selectivity in the branched multistep pathway for violacein biosynthesis,
      indicating a general applicability for the algorithm and the proposed heuristics.
      We expect that RedLibs will substantially simplify the refactoring of synthetic
      metabolic pathways. 

PMID- 27029462
TI  - Truncated Escherichia coli thioredoxin induces proliferation of human blood
      mononuclear cells and production of reactive oxygen species as well as
      proinflammatory cytokines.
AB  - Thioredoxin (Trx) is a redox protein characterized by a Trx fold. A naturally
      occurring truncated human Trx, Trx 80, which lacks the C-terminal strand-helix of
      the Trx fold, stimulates proliferation of peripheral blood mononuclear cells
      (PBMCs). It has not been clear how Trx80 gains this function. This study
      investigates whether a peptide with substantial sequence difference from Trx80,
      but retaining an abridged Trx fold can elicit PBMC proliferation. We genetically
      truncated a carboxy-terminal beta-alpha motif of Escherichia coli Trx to produce
      a peptide, Trx83, which shares low sequence identity with human Trx80. Addition
      of reduced-form Trx83 to resting human PBMCs promoted cell proliferation, while
      oxidized-form Trx83 lacked the function. By contrast, oxidized-form Trx80
      exhibited a high activity in promoting PBMC proliferation, indicating the
      importance of sequence context of an abridged thioredoxin in influencing PBMC
      proliferation. Trx83 increases cellular reactive oxygen species and
      proinflammatory cytokines TNF-alpha and IL-1beta, suggesting that Trx83 modulates
      inflammatory pathways. This notion is supported by the observation that cystine
      or cysteine abolishes the Trx83 induced PBMC proliferation. The PBMC stimulatory
      activity of Trx83 may have potential for pharmacological developments.
      SIGNIFICANCE OF THE STUDY: Elicitation of primary proliferative responses of
      PBMCs by a protein is generally difficult. We show that Escherichia coli Trx83
      with a truncated Trx fold induces PBMC proliferation, but only in the disulfide
      reduced form. In contrast, oxidized-form human Trx80 is a potent stimulator.
      These results demonstrate that the sequence context of an abridged Trx fold is
      influential in inducing PBMC proliferation. The stimulatory effect of Trx83 is
      associated with an increase of inflammatory response. The possibility of
      eliciting PBMC proliferation and switching this activity on/off by redox control
      provides a perspective for developing Trx83 as a PBMC stimulatory agent.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27029463
TI  - Risk factors for not completing health interventions and the potential impact on
      health inequalities between educational groups - a mixed method study from
      Denmark.
AB  - BACKGROUND: Individual-based interventions aim to improve patient self-management
      of chronic disease and to improve lifestyle among people at high risk, to reduce
      the prevalence of diseases contributing to health inequality. The present study
      investigates risk factors for uncompleted health interventions, via a combination
      of quantitative and qualitative methods. METHODS: From a health centre in
      Copenhagen, questionnaire data on educational level, gender, age, and
      cohabitation status from 104 participants in health interventions were used to
      examine risks for dropout. Qualitative telephone interviews further investigated
      risk factors among 17 participants who were registered as uncompleted. RESULTS:
      Our findings show that there is a significantly higher prevalence of uncompleted
      courses among participants below age 60 (OR 3.38, 95 % CI 1.08; 10.55) and an
      insignificantly higher prevalence among people with low education (OR 1.82, 95 %
      CI 0.66; 5.03). Qualitative elaboration of these findings points to low self
      control in jobs and a higher degree of comorbidity and treatment of diseases
      among the lower educated as determinants for not completing, but not lower
      motivation or less positive attitude toward the intervention itself. CONCLUSIONS:
      This study indicates a social difference in dropout, and if dropout is to be
      prevented, there is a need to acknowledge factors such as organization of the
      intervention, lack of job flexibility, and comorbidity. If these factors are not
      addressed, people with low socioeconomic status will most likely have reduced
      opportunities for making healthy choices, in this case, completing the
      intervention, and this may increase health inequality.

PMID- 27029464
TI  - Dynamic in situ observation of voltage-driven repeatable magnetization reversal
      at room temperature.
AB  - Purely voltage-driven, repeatable magnetization reversal provides a tantalizing
      potential for the development of spintronic devices with a minimum amount of
      power consumption. Substantial progress has been made in this subject especially
      on magnetic/ferroelectric heterostructures. Here, we report the in situ
      observation of such phenomenon in a NiFe thin film grown directly on a
      rhombohedral Pb(Mg1/3Nb2/3)0.7Ti0.3O3(PMN-PT) ferroelectric crystal. Under a
      cyclic voltage applied perpendicular to the PMN-PT without a magnetic field, the
      local magnetization of NiFe can be repetitively reversed through an out-of-plane
      excursion and then back into the plane. Using phase field simulations we
      interpret magnetization reversal as a synergistic effect of the metastable
      ferroelastic switching in the PMN-PT and an electrically rotatable local exchange
      bias field arising from the heterogeneously distributed NiO clusters at the
      interface. 

PMID- 27029465
TI  - Ophthalmological findings in 74 patients with mitochondrial disease.
AB  - BACKGROUND: Mitochondrial disease often manifests with ophthalmologic signs and
      symptoms. Due to the important role of mitochondria in aerobic metabolism, the
      eyes are among the more preferentially involved organs. The clinical diagnosis of
      mitochondrial disease can be facilitated by an improved knowledge of the types
      and magnitude of their various manifestations. The aim of this study was to
      describe the ophthalmological manifestations of patients with mitochondrial
      diseases that are currently not well elucidated. METHODS: From a database of
      patients with verified primary mitochondrial disease (n = 81) who had visited our
      institution we identified 74 patients who had ophthalmologic examinations.
      Demographic, clinical, and ophthalmologic data were collected. Institutional
      review board approval was obtained. RESULTS: A total of 74 patients were
      identified with Leigh disease, MELAS, MERRF, CPEO, Pearson/Kearns-Sayre syndrome,
      as well as other mtDNA point mutations, deletions, depletions, and mutations.
      Overall, 26 of the 74 patients (35%) had one or more ophthalmological
      abnormalities. Retinal pigmentary changes were present in 12/74 (16%) of
      patients. Partial or total optic atrophy (OA) was noted in 8/74 (10%) of
      patients. Decreased extra-ocular movement (EOM) was noted in 6/74 (8%) of
      patients. Other ophthalmological findings included macular atrophy (2/74),
      macular dystrophy (1/74), and visual field defects (1/74). CONCLUSIONS: Over one
      third of our cohort of patients with mitochondrial disorders had ophthalmological
      manifestations, some of which affected vision significantly. Eye examinations are
      critical in patients with mitochondrial disease so that complete assessments of
      the effects of the underlying mutations are uncovered and the appropriate
      counseling and care are given.

PMID- 27029466
TI  - Kelussia odoratissima Mozaff attenuates thromboembolic brain injury, possibly due
      to its Z-ligustilide content.
AB  - PRIMARY OBJECTIVE: Essential oil (EO) of Kelussia odoratissima Mozaff, whose main
      composition is Z-ligustilide, has been shown to have strong antioxidant and anti
      inflammatory effects and potent neuroprotective properties. RESEARCH DESIGN: This
      study examined whether or not the EO could ameliorate brain damage and
      behavioural dysfunction in a thromboembolic model of stroke in rats and compare
      its effects to that of the purified Z-ligustilide. METHODS AND PROCEDURES: Stroke
      was induced in rats by middle cerebral artery occlusion using an autologous pre
      formed clot. EO (10 mg kg(-1) and 45 mg kg(-1)) and Z-ligustilide (20 mg kg(-1))
      were injected intraperitoneally 1 h prior to embolization. Behavioural scores,
      infarct size and brain oedema, as well as the level of tumour necrosis factor
      alpha (TNF-alpha), malondialdehyde, glutathione, catalase and superoxide
      dismutase activity were determined in the ipsilateral cortex 24 hours following
      stroke induction. MAIN OUTCOMES AND RESULTS: EO (45 mg kg(-1)), statistically
      similar to Z-ligustilide (20 mg kg(-1)), curtailed brain infarction and oedema,
      improved behavioural scores and prevented enhanced oxidative stress and TNF-alpha
      level in the ischaemic brain tissues. CONCLUSIONS: The findings provide the first
      evidence of effectiveness of the extract in a thromboembolic model of stroke,
      whose action can be mediated, at least in part, by the antioxidative and anti
      inflammatory mechanisms.

PMID- 27029467
TI  - Ectomycorrhizal fungal richness declines towards the host species' range edge.
AB  - Plant range boundaries are generally considered to reflect abiotic conditions;
      however, a rise in negative or decline in positive species interactions at range
      margins may contribute to these stable boundaries. While evidence suggests that
      pollinator mutualisms may decline near range boundaries, little is known about
      other important plant mutualisms, including microbial root symbionts. Here, we
      used molecular methods to characterize root-associated fungal communities in
      populations of two related temperate tree species from across the species' range
      in the eastern United States. We found that ectomycorrhizal fungal richness on
      plant roots declined with distance from the centre of the host species range.
      These patterns were not evident in nonmycorrhizal fungal communities on roots nor
      in fungal communities in bulk soil. Climatic and soil chemical variables could
      not explain these biogeographic patterns, although these abiotic gradients
      affected other components of the bulk soil and rhizosphere fungal community.
      Depauperate ectomycorrhizal fungal communities may represent an underappreciated
      challenge to marginal tree populations, especially as rapid climate change pushes
      these populations outside their current climate niche.

PMID- 27029468
TI  - Rheumatoid meningitis.
AB  - Rheumatoid meningitis is a rare, potentially treatable condition that can mimic a
      wide range of neurological conditions, including vascular syndromes and
      encephalopathies. Despite a concurrent history of rheumatoid arthritis, patients
      often have no active synovitis. Here we describe a patient with rheumatoid
      meningitis who presented to a hyperacute stroke unit with dysarthria on waking
      and transient facial droop. 

PMID- 27029469
TI  - Using international human rights law to improve child health in low-income
      countries: a framework for healthcare professionals.
AB  - BACKGROUND: The Committee on Economic, Social and Cultural Rights states that the
      right to health is closely related to, and dependent upon, the realization of
      other human rights, including the right to food, water, education and shelter
      which are important determinants of health. Children's healthcare workers in low
      income settings may spend the majority of their professional lives trying to
      mitigate deficiencies of these rights but have little influence over them. In
      order to advocate successfully at a local level, we should be aware of the
      proportion of children living in our catchment population who do not have access
      to their basic rights. In order to carry out a rights audit, a framework within
      which healthcare workers could play their part is required, as is an agreed
      minimum core of rights, a timeframe and a set of indicators. DISCUSSION: A
      framework to assess how well states and their developmental partners are adhering
      to human rights principles is discussed, including the role that a healthcare
      worker might optimally play. A minimum core of economic and social rights seeks
      to establish a legal minimum set of protections, which should be available with
      immediate effect and applicable to all nations despite very different resources.
      Minimum core rights and the impact that progressive realisation may have had on
      the right to health is discussed, including what they should include from the
      perspective of children's health. A set of absolute rights are suggested, based
      on physiological needs and aligned with the corresponding articles of the United
      Nations Convention on the Rights of the Child. The development indicators which
      are likely to be used to monitor progress towards the Sustainable Development
      Goals is suggested as a way to monitor rights. We consider the ways in which the
      healthcare worker could use a rights audit to advocate with, and for their
      community. These audits could achieve several objectives. They may legitimise
      healthcare workers' interests in the determinants of health and, as they are
      often highly respected by their community, this may facilitate them to be agents
      for change at a local level. This may raise awareness on basic human rights and
      their importance to health and contribute to a needed change in mind-set from one
      of development needs to absolute rights. The results may catalyse colleagues to
      analyse further the upstream reasons why children, and the families in which they
      live, are not having their rights met.

PMID- 27029470
TI  - Sample size calculation while controlling false discovery rate for differential
      expression analysis with RNA-sequencing experiments.
AB  - BACKGROUND: RNA-Sequencing (RNA-seq) experiments have been popularly applied to
      transcriptome studies in recent years. Such experiments are still relatively
      costly. As a result, RNA-seq experiments often employ a small number of
      replicates. Power analysis and sample size calculation are challenging in the
      context of differential expression analysis with RNA-seq data. One challenge is
      that there are no closed-form formulae to calculate power for the popularly
      applied tests for differential expression analysis. In addition, false discovery
      rate (FDR), instead of family-wise type I error rate, is controlled for the
      multiple testing error in RNA-seq data analysis. So far, there are very few
      proposals on sample size calculation for RNA-seq experiments. RESULTS: In this
      paper, we propose a procedure for sample size calculation while controlling FDR
      for RNA-seq experimental design. Our procedure is based on the weighted linear
      model analysis facilitated by the voom method which has been shown to have
      competitive performance in terms of power and FDR control for RNA-seq
      differential expression analysis. We derive a method that approximates the
      average power across the differentially expressed genes, and then calculate the
      sample size to achieve a desired average power while controlling FDR. Simulation
      results demonstrate that the actual power of several popularly applied tests for
      differential expression is achieved and is close to the desired power for RNA-seq
      data with sample size calculated based on our method. CONCLUSIONS: Our proposed
      method provides an efficient algorithm to calculate sample size while controlling
      FDR for RNA-seq experimental design. We also provide an R package ssizeRNA that
      implements our proposed method and can be downloaded from the Comprehensive R
      Archive Network ( http://cran.r-project.org ).

PMID- 27029471
TI  - Influence of obstructive sleep apnea on ischemia-modified albumin levels and
      carotid intima-media thickness.
AB  - Obstructive sleep apnea (OSA) is associated with an increased risk of
      atherosclerosis. Carotid intima-media thickness (CIMT) is strongly associated
      with the presence of significant risk factors for cardiovascular disturbances. A
      disturbance in the oxidative/antioxidative balance is involved in the
      pathogenesis of OSA and cardiovascular diseases. Ischemia-modified albumin (IMA)
      is suggested as a novel marker of oxidative stress; IMA can be defined as
      decreased binding of transitional metal ions to serum albumin in oxidative
      status. The purpose of this research was to evaluate the influence of OSA on IMA
      levels and CIMT. In total, 61 individuals with OSA with no comorbidities and 24
      healthy controls with a similar body mass index and age were enrolled in this
      study. Serum levels of IMA, CIMT (estimated radiologically), and polysomnographic
      parameters, were determined and interpreted. Serum IMA levels were significantly
      higher in individuals with OSA compared with the control group (p=0.0003). CIMT
      was significantly higher in the OSA group compared with the control group (0.88+/
      0.26 mm vs 0.75+/-0.17 mm, p=0.005). The CIMT and serum IMA levels were
      positively correlated with the apnea-hypopnea index (r=0.35 and r=0.32,
      respectively), and with the oxygen desaturation index (r=0.34 and r=0.29,
      respectively) at baseline. Increased IMA levels and CIMT may be related to
      increased oxidative stress and risk of atherosclerosis in individuals with OSA.

PMID- 27029472
TI  - The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling.
AB  - Transmembrane protein 18 (TMEM18) is an ill-described, obesity-related gene, but
      few studies have explored its molecular function. We found single-nucleotide
      polymorphism data, suggesting that TMEM18 may be involved in the
      regulation/physiology of metabolic syndrome based on associations with insulin,
      homeostatic model assessment-beta (HOMAbeta), triglycerides, and blood sugar. We
      then found an ortholog in the Drosophila genome, knocked down Drosophila Tmem18
      specifically in insulin-producing cells, and tested for its effects on metabolic
      function. Our results suggest that TMEM18 affects substrate levels through
      insulin and glucagon signaling, and its downregulation induces a metabolic state
      resembling type 2 diabetes. This work is the first to experimentally describe the
      metabolic consequences of TMEM18 knockdown, and further supports its association
      with obesity.

PMID- 27029474
TI  - The Relationship Between the Religious Beliefs of the Diabetic Patients and
      Depression in a Diabetes Clinic in Iran.
AB  - Nowadays, diabetes is prevalent, and it can leave severe psychotic effects and
      causes depression; thus, it is necessary to consider effective factors to fight
      against diabetic patients' mental conditions. It seems that the role of religion
      is significant, and by augmenting religious attitudes, diabetic patient's
      depression intensity can be decreased. The purpose of the present study is to
      examine the relationship between religious beliefs and depression of diabetic
      patients in diabetes clinic of Ali Asghar Hospital in Zahedan. This is a
      descriptive analytical and cross-sectional study. Out of total 350 diabetic
      patients, 70 were selected by easy sampling method. Data gathering tool was
      Bach's religious beliefs and depression standard questionnaires. K2 statistical
      test and Pearson's correlation index have been used for data analysis. SPSS
      software version 16 was used to analyze the data. The results of the study showed
      that there was not any relationship among age, sex, education, illness duration
      and family member's history of depression and depression. Results of the study
      showed that stronger religious beliefs decrease the depression severity (P <
      0.001). Therefore, it is necessary to strengthen patient's religious attitudes by
      proper plans to decrease depression, and some strategies are presented in the
      study for these plans.

PMID- 27029473
TI  - Normal gonadotropin production and fertility in gonadotrope-specific Bmpr1a
      knockout mice.
AB  - Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by
      transforming growth factorbetasuperfamily ligands, most notably the activins and
      inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHbeta subunit (Fshb)
      expression in immortalized murine gonadotrope-like LbetaT2 cells and in primary
      murine or ovine primary pituitary cultures. BMP2 signals preferentially via the
      BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro
      Here, we used a Cre-lox approach to assess BMPR1A's role in FSH synthesis in mice
      in vivo Gonadotrope-specific Bmpr1a knockout animals developed normally and had
      reproductive organ weights comparable with those of controls. Knockouts were
      fertile, with normal serum gonadotropins and pituitary gonadotropin subunit mRNA
      expression. Cre-mediated recombination of the floxed Bmpr1a allele was efficient
      and specific, as indicated by PCR analysis of diverse tissues and isolated
      gonadotrope cells. Furthermore, BMP2 stimulation of inhibitor of DNA binding 3
      expression was impaired in gonadotropes isolated from Bmpr1a knockout mice,
      confirming the loss of functional receptor protein in these cells. Treatment of
      purified gonadotropes with small-molecule inhibitors of BMPR1A (and the related
      receptors BMPR1B and ACVR1) suppressed Fshb mRNA expression, suggesting that an
      autocrine BMP-like molecule might regulate FSH synthesis. However, deletion of
      Bmpr1a and Acvr1 in cultured pituitary cells did not alter Fshb expression,
      indicating that the inhibitors had off-target effects. In sum, BMPs or related
      ligands acting via BMPR1A or ACVR1 are unlikely to play direct physiological
      roles in FSH synthesis by murine gonadotrope cells.

PMID- 27029475
TI  - Screening for fatigue in adolescent and young adult pediatric brain tumor
      survivors: accuracy of a single-item screening measure.
AB  - PURPOSE: Cancer-related fatigue (CRF) is one of the most commonly reported and
      distressing symptoms experienced by adolescent and young adult (AYA) cancer
      survivors. While national guidelines have recommended screening for CRF during
      routine follow-up appointments, the validity of using a one-item screening
      measure for fatigue has not been examined with AYA brain tumor survivors. The
      purpose of this study is to assess how well a single-item fatigue screen could
      identify clinically significant fatigue in childhood brain tumor survivors.
      METHODS: A single-item measure, the Fatigue Thermometer (FT), was compared with a
      more in-depth measure, the Multidimensional Fatigue Scale (MFS), in a cohort of
      AYA pediatric brain tumor survivors. One hundred and forty-two survivors (aged 12
      32 years) completed the two instruments. RESULTS: Forty-two survivors were
      identified on the MFS as having clinically significant fatigue, but the FT was
      not found to be an accurate tool for identifying these cases. Although receiver
      operating characteristic curve analysis of FT ratings against the MFS criterion
      indicated good concordance between measures, no cutoff score on the FT was
      identified that resulted in acceptable sensitivity and specificity. CONCLUSIONS:
      Results from this study suggest that a single-item screening measure for fatigue
      is not able to reliably identify clinically significant fatigue in AYA brain
      tumor survivors.

PMID- 27029476
TI  - Bisphosphonate-related osteonecrosis of the jaw: a review of the potential
      efficacy of low-level laser therapy.
AB  - Osteonecrosis of the jaw (ONJ) resulting from administration of bisphosphonates
      (BP) or denosumab is a rare but severe complication in cancer patients. Complete
      remission depends on the stage of ONJ; it can be estimated in the range of 20-30
      %. Low-level laser therapy (LLLT) is a logical additional option, as it has been
      recognized effective for the management of chemotherapy and/or radiotherapy
      induced mucositis. LLLT irradiation has anti-inflammatory actions and thus can
      help to control pain, as well as biostimulating properties with favorable actions
      on bacterial control and wound healing. We review the results of seven published
      studies of LLLT in BP-associated ONJ. LLLT results in an overall response rate of
      55 % superior to that observed in controls (30 %). Our review suggests that there
      might be an advantage to add LLLT to the "classical" management of ONJ. This
      therapy is easy to administer and is not associated with any known side effects.
      Further research is needed to remove any doubt of protection or enhancement of
      carcinogenic processes. We believe that prospective well-controlled studies of
      LLLT in ONJ are warranted. If the positive results are confirmed, it would
      represent a great improvement for the quality of life of many patients.

PMID- 27029477
TI  - Health-related quality of life in patients with neuroendocrine tumors: an
      investigation of treatment type, disease status, and symptom burden.
AB  - INTRODUCTION: Neuroendocrine tumors (NETs) are malignant solid tumors arising in
      hormone-secreting tissue. They have historically been very difficult to treat,
      and advanced NETs are considered incurable. Surgery is the only potentially
      curative treatment option, though research is ongoing, investigating the efficacy
      of targeted therapies combined with more traditional chemotherapies. Frequent
      bowel movements and episodes of flushing are the most common symptoms. METHODS:
      The present study reports data from an anonymous patient survey of 663 eligible
      NET patients, identified with the assistance of patient advocacy groups. This
      study investigated the impact of treatment (surgery alone; surgery plus
      somatostatin analogue; other treatments) on quality of life (QOL). Finally, we
      investigate whether recurrent disease results in poorer QOL compared to disease
      treated curatively with surgery and remaining in remission. RESULTS AND
      DISCUSSION: Results suggest that increased frequency of bowel movements and
      presence of any flushing symptoms are correlated with decreased quality of life.
      Treatment groups differed on most Patient Reported Outcomes Measurement
      Information System (PROMIS) global health and PROMIS-29 scores, including
      physical function, fatigue, pain, social function, and general physical and
      mental health, with the surgery group reporting significantly better scores than
      the other groups (effect size of differences ranged from 0.28 to 0.54). This may
      be possibly due to effective symptom control reached for these patients through
      surgery alone. After adjustment for carcinoid syndrome, the association with the
      treatment group disappeared for all domains except physical functioning. In terms
      of disease status, patients with recurrent disease reported poorer physical,
      social, and mental functions. Depression scores were similar between groups;
      however, patients with recurrent disease reported significantly higher anxiety
      compared to those with no current NET. Physical functioning was even more
      markedly different between groups, with recurrent NET patients reporting
      significantly impaired overall physical function, impaired sleep, and significant
      fatigue compared to those with no current NET. To our knowledge, this is the
      first study to comprehensively examine the effect of treatment group, disease
      status, and symptom burden on the quality of life in NET patients in a large
      sample. Limitations and future research directions are discussed.

PMID- 27029478
TI  - 'Do-It-Yourself' Healthcare? Quality of Health and Healthcare Through Wearable
      Sensors.
AB  - Wearable sensors are an integral part of the new telemedicine concept supporting
      the idea that Information Technologies will improve the quality and efficiency of
      healthcare. The use of sensors in diagnosis, treatment and monitoring of patients
      not only potentially changes medical practice but also one's relationship with
      one's body and mind, as well as the role and responsibilities of patients and
      healthcare professionals. In this paper, we focus on knowledge assessment of the
      online communities of Fitbit (a commercial wearable device) and the Quantified
      Self movement. Through their online forums, we investigate how users' knowledge
      claims, shared experiences and imaginations about wearable sensors interrogate or
      confirm the narratives through which they are introduced to the publics. Citizen
      initiatives like the Quantified Self movement claim the right to 'own' the sensor
      generated data. But how these data can be used through traditional healthcare
      systems is an open question. More importantly, wearable sensors trigger a social
      function that is transformative of the current idea of care and healthcare,
      focused on sharing, socialising and collectively reflecting about individual
      problems. Whether this is aligned with current policy making about healthcare,
      whose central narrative is focused on efficiency and productivity, is to be seen.

PMID- 27029479
TI  - Medical leadership in the 21st century.
AB  - OBJECTIVE: Psychiatry as a discipline and as a profession stands at the cusp of
      major challenges in many areas including social, biological and psychological
      spheres. The practice of psychiatry is affected by ideologically driven policies
      by politicians, and the continuing long-lasting impact of the global economic
      downturn along with new developments in health care delivery. Changing biological
      factors include better understanding of brain structures and functioning and
      potential developments in psychopharmacogenomics. Social changes facing
      psychiatry include globalisation and rapid urbanisation. Psychological changes
      include therapies without therapists and the impact of social media and the
      information age. The current paper explores these challenges and the
      opportunities for psychiatrists to provide leadership in a number of settings.
      CONCLUSION: Leadership skills are essential skills for psychiatrists, and enable
      an individual to plan and deliver services, and also help them to lead not only
      clinical teams but organisations and institutions. Psychiatrists are best placed
      because of the breadth of the training they undergo and their communication
      skills. Leadership is markedly different from managerial skills, although there
      may be a small degree of overlap.

PMID- 27029480
TI  - YouTube provides irrelevant information for the diagnosis and treatment of hip
      arthritis.
AB  - PURPOSE: YouTube is increasingly becoming a key source for people to satisfy the
      need for additional information concerning their medical condition. This study
      analyses the completeness of accurate information found on YouTube pertaining to
      hip arthritis. METHODS: The present study analyzed 133 YouTube videos using the
      search terms: hip arthritis, hip arthritis symptoms, hip arthritis diagnosis, hip
      arthritis treatment and hip replacement. Two quality assessment checklists with a
      scale of 0 to 12 points were developed to evaluate available video content for
      the diagnosis and the treatment of hip arthritis. Videos were grouped into poor
      quality (grade 0-3), moderate quality (grade 4-7) and excellent quality (grade 8
      12), respectively. Three independent observers assessed all videos using the new
      grading system and independently scored all videos. Discrepancies regarding the
      categories were clarified by consensus discussion. For intra-observer
      reliabilities, grading was performed at two occasions separated by four weeks.
      RESULTS: Eighty-four percent (n = 112) had a poor diagnostic information quality,
      14% (n = 19) a moderate quality and only 2% (n = 2) an excellent quality,
      respectively. In 86% (n = 114), videos provided poor treatment information
      quality. Eleven percent (n = 15) of videos had a moderate quality and only 3% (n
      = 4) an excellent quality, respectively. CONCLUSIONS: The present study
      demonstrates that YouTube is a poor source for accurate information pertaining to
      the diagnosis and treatment of hip arthritis. These finding are of high relevance
      for clinicians as videos are going to become the primary source of information
      for patients. Therefore, high quality educational videos are needed to further
      guide patients on the way from the diagnosis of hip arthritis to its proper
      treatment.

PMID- 27029482
TI  - Holistic face perception is modulated by experience-dependent perceptual
      grouping.
AB  - What role do general-purpose, experience-sensitive perceptual mechanisms play in
      producing characteristic features of face perception? We previously demonstrated
      that different-colored, misaligned framing backgrounds, designed to disrupt
      perceptual grouping of face parts appearing upon them, disrupt holistic face
      perception. In the current experiments, a similar part-judgment task with
      composite faces was performed: face parts appeared in either misaligned,
      different-colored rectangles or aligned, same-colored rectangles. To investigate
      whether experience can shape impacts of perceptual grouping on holistic face
      perception, a pre-task fostered the perception of either (a) the misaligned,
      differently colored rectangle frames as parts of a single, multicolored polygon
      or (b) the aligned, same-colored rectangle frames as a single square shape. Faces
      appearing in the misaligned, differently colored rectangles were processed more
      holistically by those in the polygon-, compared with the square-, pre-task group.
      Holistic effects for faces appearing in aligned, same-colored rectangles showed
      the opposite pattern. Experiment 2, which included a pre-task condition fostering
      the perception of the aligned, same-colored frames as pairs of independent
      rectangles, provided converging evidence that experience can modulate impacts of
      perceptual grouping on holistic face perception. These results are surprising
      given the proposed impenetrability of holistic face perception and provide
      insights into the elusive mechanisms underlying holistic perception.

PMID- 27029481
TI  - Increased risk of vertebral fracture in patients with diabetes: a meta-analysis
      of cohort studies.
AB  - PURPOSE: The relationship between diabetes and risk of fracture has been reported
      differently in study design and risk estimates, and the relationship between
      diabetes and risk of vertebral fracture remained unclear. Therefore, we performed
      a meta-analysis of prospective or retrospective cohort studies to assess the
      potential relationship between diabetes and vertebral fracture. METHODS: We
      searched medical databases for prospective or retrospective cohort studies on the
      association between diabetes and vertebral fracture risk. Pooled relative risks
      (RR) and corresponding 95 % confidence intervals (95 % CI) were calculated with a
      random-effects model of meta-analysis. RESULTS: Meta-analysis of eight studies
      showed that the pooled RR of vertebral fracture for diabetic individuals was 2.03
      (95 % CI 1.60-2.59; p < 0.0001). Subgroup analysis by gender showed that the
      corresponding RRs for male and female were 2.70 (95 % CI 1.34-5.43; p = 0.005)
      and 1.93 (95 % CI 1.18-3.13; p = 0.008), respectively. Subgroup analysis by study
      design showed that the corresponding RRs for prospective design and retrospective
      design were 1.81 (95  % CI 1.19-2.75; p = 0.006) and 2.23 (95  % CI 1.60-3.10; p
      < 0.0001), respectively. Subgroup analysis by time of follow-up showed that the
      RR of vertebral fracture for patients with >20 and <20 years of follow-up were
      2.23 (95 % CI 1.98-3.62; p < 0.0001) and 1.67 (95  % CI 1.29-2.16; p < 0.0001),
      respectively. CONCLUSIONS: Diabetes is an independent risk factor for vertebral
      fracture, primarily being due to diabetic osteoporosis.

PMID- 27029483
TI  - A patient with muscle weakness.

PMID- 27029484
TI  - Long-term outcome of pediatric kidney transplantation: A single-center experience
      from Greece.
AB  - Pediatric kidney Tx has critically altered the outcome in ESRD pediatric
      patients. The aims of this study were to determine long-term graft and patient
      survival in a homogeneous ethnic population. We reviewed the medical charts of
      pediatric kidney Tx performed between 1990 and 2012 in Greece. Seventy-five
      kidney Txs were performed from LRD and 62 from DD. The 10- and 20-yr graft
      survival was higher in LRD Tx compared with DD Tx. Both patient and graft
      survival at 10 and 20 yr after Tx were similar in LRD Tx from grandparents
      compared with parents (92.9% vs. 93.4% 20-yr patient survival, 71.4% vs. 78.7%
      and 57.1% vs. 72.1%, 10- and 20-yr graft survival, respectively). However, there
      was a decreasing tendency in LRD Tx rates in period 2001-2012 compared with
      period 1990-2000 (47.1% vs. 62.7%). Risk factors for poor five-yr graft survival
      were DD Tx, and induction treatment with ALG compared with basiliximab, but their
      effect attenuated at 10 yr after Tx. In conclusion, Tx from LRD may offer
      efficient survival outcomes irrespective of donor age, suggesting that even older
      LRD could be an excellent option for the 1st kidney Tx in children and
      adolescents.

PMID- 27029485
TI  - Caffeic Acid Inhibits Chronic UVB-Induced Cellular Proliferation Through JAK
      STAT3 Signaling in Mouse Skin.
AB  - Signal transducers and activators of transcription 3 (STAT3) play a critical role
      in inflammation, proliferation and carcinogenesis. Inhibition of JAK-STAT3
      signaling is proved to be a novel target for prevention of UVB-induced skin
      carcinogenesis. In this study, chronic UVB irradiation (180 mJ cm(-2) ; weekly
      thrice for 30 weeks) induces the expression of IL-10 and JAK1 that eventually
      activates the STAT3 which leads to the transcription of proliferative and
      antiapoptotic markers such as PCNA, Cyclin-D1, Bcl2 and Bcl-xl, respectively.
      Caffeic acid (CA) inhibits JAK-STAT3 signaling, thereby induces apoptotic cell
      death by upregulating Bax, Cytochrome-C, Caspase-9 and Caspase-3 expression in
      mouse skin. Furthermore, TSP-1 is an antiangiogeneic protein, which is involved
      in the inhibition of angiogenesis and proliferation. Chronic UVB exposure
      decreased the expression of TSP-1 and pretreatment with CA prevented the UVB
      induced loss of TSP-1 in UVB-irradiated mouse skin. Thus, CA offers protection
      against UVB-induced photocarcinogenesis probably through modulating the JAK-STAT3
      in the mouse skin.

PMID- 27029487
TI  - Clinical Experience With Deferiprone Treatment for Friedreich Ataxia.
AB  - Friedreich ataxia is an inherited disorder characterized by degeneration of the
      peripheral and central nervous system and hypertrophic cardiomyopathy. Homozygous
      mutations in the frataxine (FXN) gene reduce expression of frataxin and cause
      accumulation of iron in the mitochondria. Deferiprone, an oral iron chelator, has
      been shown effective in cell and animal models of Friedreich ataxia. The results
      of a 6-month randomized, double blind placebo-controlled study suggested that
      deferiprone 20 mg/kg/day may reduce disease progression. The authors present
      their experience of 5 Friedreich ataxia patients treated with deferiprone (20
      mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24
      months, under off-label authorization. The patients were monitored for laboratory
      parameters, cardiac assessment, neurological evaluations, and quality of life.
      The authors conclude that combined therapy of a low dose of deferiprone with
      idebenone is relatively safe, might improve neurological function, and seems to
      improve heart hypertrophy, warranting further studies.

PMID- 27029486
TI  - Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the
      intestinal barrier in inflammatory bowel disease.
AB  - BACKGROUND: The IL23/Th17 pathway is essential for the onset of inflammatory
      bowel disease (IBD), yet the specific mechanism by which this pathway initiates
      the disease remains unknown. In this study, we identify the mechanisms that
      mediate cross-talk between the IL23 pathway and the intestinal barrier in IBD.
      RESULTS: The downstream targets of the IL23 pathway were identified by RNA array
      profiling and confirmed by immunohistochemical staining. The role of miRNAs that
      interact with IL23 was explored in mice with TNBS-induced colitis. Claudin-8
      (CLDN8), a multigene family protein that constitutes the backbone of tight
      junctions, was identified as a novel target of IL23 in IBD. CLDN8 was
      significantly downregulated in IBD patients with inflamed colonic mucosa, and in
      trinitrobenzene sulphonic acid (TNBS) induced colitis in mice. Therapeutic
      treatment of colitis in mice using an IL23 antibody restored CLDN8 abundance, in
      parallel with recovery from colitis. In addition, we identify miR-223 as a novel
      mediator of the crosstalk between the IL23 signal pathway and CLDN8 in the
      development of IBD. MiR-223 was upregulated in IBD, and its activity was
      regulated through the IL23 pathway. Antagomir inhibition of miR-223 reactivated
      CLDN8 and improved a number of signs associated with TNBS-induced colitis in
      mice. CONCLUSIONS: Our study characterizes a new mechanistic pathway in IBD, in
      which miR-223 interacts with the IL23 pathway by targeting CLDN8. Strategies
      designed to disrupt this interaction may provide novel therapeutic agents for the
      management of IBD.

PMID- 27029488
TI  - Development of real-time reverse transcriptase qPCR assays for the detection of
      Punta Toro virus and Pichinde virus.
AB  - BACKGROUND: Research with high biocontainment pathogens such as Rift Valley fever
      virus (RVFV) and Lassa virus (LASV) is expensive, potentially hazardous, and
      limited to select institutions. Surrogate pathogens such as Punta Toro virus
      (PTV) for RVFV infection and Pichinde virus (PICV) for LASV infection allow
      research to be performed under more permissive BSL-2 conditions. Although used as
      infection models, PTV and PICV have no standard real-time RT-qPCR assays to
      detect and quantify pathogenesis. PTV is also a human pathogen, making a
      standardized detection assay essential for biosurveillance. Here, we developed
      and characterized two real-time RT-qPCR assays for PICV and PTV by optimizing
      assay conditions and measuring the limit of detection (LOD) and performance in
      multiple clinical matrices. METHODS: Total nucleic acid from virus-infected Vero
      E6 cells was used to optimize TaqMan-minor groove binder (MGB) real-time RT-qPCR
      assays. A 10-fold dilution series of nucleic acid was used to perform analytical
      experiments with 60 replicates used to confirm assay LODs. Serum and whole blood
      spiked with 10-fold dilutions of PTV and PICV virus were assessed as matrices in
      a mock clinical context. The Cq, or cycle at which the fluoresce of each sample
      first crosses a threshold line, was determined using the second derivative method
      using Roche LightCycler 480 software version 1.5.1. Digital droplet PCR (ddPCR)
      was utilized to quantitatively determine RNA target counts/MUl for PTV and PICV.
      RESULTS: Optimized PTV and PICV assays had LODs of 1000 PFU/ml and 100 PFU/ml,
      respectively, and this LOD was confirmed in 60/60 (PTV) and 58/60 (PICV) positive
      replicates. Preliminary mock clinical LODs remained consistent in serum and whole
      blood for PTV and PICV at 1000 PFU/ml and 100 PFU/ml. An exclusivity panel showed
      no cross reaction with near neighbors. CONCLUSIONS: PTV and PICV Taq-man MGB
      based real-time RT-qPCR assays developed here showed relevant sensitivity and
      reproducibility in samples extracted from a variety of clinical matrices. These
      assays will be useful as a standard by researchers for future experiments
      utilizing PTV and PICV as infection models, offering the ability to track
      infection and viral replication kinetics during research studies.

PMID- 27029489
TI  - Lifestyle INtervention for Diabetes prevention After pregnancy (LINDA-Brasil):
      study protocol for a multicenter randomized controlled trial.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM), a hyperglycemic state detected
      during pregnancy, is an established risk factor for diabetes. However, treatment
      during pregnancy in and of itself is not able to eliminate this risk, and a
      considerable fraction of women with GDM will develop frank diabetes in the decade
      following pregnancy. Our aim is to conduct a multicenter randomized controlled
      trial to investigate the effectiveness of a lifestyle intervention program
      implemented after a pregnancy complicated by GDM in delaying or preventing the
      development of type 2 diabetes. METHODS: Women aged 18 or older identified as
      having recent GDM are recruited and followed by telephone to assess eligibility
      for the trial. To be eligible, women must have used insulin during pregnancy or
      present intermediate hyperglycemia postpartum. Women are encouraged to enter the
      trial as early as 10 weeks, and are permitted to do so up to 2 years after a
      pregnancy with GDM. An estimated 740 women will be randomized to either
      conventional care or to coach-based interventions focused on breastfeeding,
      weight loss, healthy eating, and increased physical activity, and predominantly
      delivered by telephone. Women are followed annually to detect new onset diabetes,
      the primary outcome, and additional secondary outcomes which include reversion to
      normoglycemia, weight loss, physical activity and fitness, and insulin
      resistance. DISCUSSION: Though previous studies have demonstrated that type 2
      diabetes can be delayed or prevented, no study has yet demonstrated the
      feasibility and effectiveness of similar interventions implemented in the
      postpartum period for women with recent GDM. If shown to be successful, this
      approach could become an important means of preventing diabetes in primary care
      settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02327286;
      Registered 23 December 2014.

PMID- 27029490
TI  - Risks and benefits of psychotropic medication in pregnancy: cohort studies based
      on UK electronic primary care health records.
AB  - BACKGROUND: Although many women treated with psychotropic medication become
      pregnant, no psychotropic medication has been licensed for use in pregnancy. This
      leaves women and their health-care professionals in a treatment dilemma, as they
      need to balance the health of the woman with that of the unborn child. The aim of
      this project was to investigate the risks and benefits of psychotropic medication
      in women treated for psychosis who become pregnant. OBJECTIVE(S): (1) To provide
      a descriptive account of psychotropic medication prescribed before pregnancy,
      during pregnancy and up to 15 months after delivery in UK primary care from 1995
      to 2012; (2) to identify risk factors predictive of discontinuation and
      restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers
      and antipsychotic medication; (3) to examine the extent to which pregnancy is a
      determinant for discontinuation of psychotropic medication; (4) to examine
      prevalence of records suggestive of adverse mental health, deterioration or
      relapse 18 months before and during pregnancy, and up to 15 months after
      delivery; and (5) to estimate absolute and relative risks of adverse maternal and
      child outcomes of psychotropic treatment in pregnancy. DESIGN: Retrospective
      cohort studies. SETTING: Primary care. PARTICIPANTS: Women treated for psychosis
      who became pregnant, and their children. INTERVENTIONS: Treatment with
      antipsychotics, lithium or anticonvulsant mood stabilisers. MAIN OUTCOME
      MEASURES: Discontinuation and restarting of treatment; worsening of mental
      health; acute pre-eclampsia/gestational hypertension; gestational diabetes;
      caesarean section; perinatal death; major congenital malformations; poor birth
      outcome (low birthweight, preterm birth, small for gestational age, low Apgar
      score); transient poor birth outcomes (tremor, agitation, breathing and muscle
      tone problems); and neurodevelopmental and behavioural disorders. DATA SOURCES:
      Clinical Practice Research Datalink database and The Health Improvement Network
      primary care database. RESULTS: Prescribing of psychotropic medication was
      relatively constant before pregnancy, decreased sharply in early pregnancy and
      peaked after delivery. Antipsychotic and anticonvulsant treatment increased over
      the study period. The recording of markers of worsening mental health peaked
      after delivery. Pregnancy was a strong determinant for discontinuation of
      psychotropic medication. However, between 40% and 76% of women who discontinued
      psychotropic medication before or in early pregnancy restarted treatment by 15
      months after delivery. The risk of major congenital malformations, and
      neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers)
      users was twice that in users of other anticonvulsants. The risks of adverse
      maternal and child outcomes in women who continued antipsychotic use in pregnancy
      were not greater than in those who discontinued treatment before pregnancy.
      LIMITATIONS: A few women would have received parts of their care outside primary
      care, which may not be captured in this analysis. Likewise, the analyses were
      based on prescribing data, which may differ from usage. CONCLUSIONS: Psychotropic
      medication is prescribed before, during and after pregnancy. Many women
      discontinue treatment before or during early pregnancy and then restart again in
      late pregnancy or after delivery. Our results support previous associations
      between valproate and adverse child outcomes but we found no evidence of such an
      association for antipsychotics. FUTURE WORK: Future research should focus on (1)
      curtailing the use of sodium valproate; (2) estimating the benefits of
      psychotropic drug use in pregnancy; and (3) investigating the risks associated
      with lifestyle choices that are more prevalent among women using psychotropic
      drugs. FUNDING DETAILS: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 27029491
TI  - A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple
      Myeloma with Extramedullary Involvement.
AB  - PURPOSE: Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma,
      and both its surface expression and its biologic significance as key sensor of
      the unfolded protein response make GRP78 an ideal candidate for immunotherapeutic
      intervention. The monoclonal antibody PAT-SM6 targets surface GRP78 and leads to
      disease stabilization when used as single agent in a clinical trial. In this
      article, we evaluated expression of GRP78 in relapsed-refractory disease and
      explored PAT-SM6 therapy in combination regimens. EXPERIMENTAL DESIGN: GRP78
      expression was immunohistochemically analyzed during disease progression and
      development of drug resistance throughout different stages of multiple myeloma.
      Activity of PAT-SM6 was evaluated in combination with anti-multiple myeloma
      agents lenalidomide, bortezomib, and dexamethasone in vitro Finally, we report on
      a multiple myeloma patient with relapsed-refractory disease treated with PAT-SM6
      in combination with bortezomib and lenalidomide. RESULTS: Although sGRP78
      expression was present at all stages, it increased with disease progression and
      was even strongly elevated in patients with drug-resistant and extramedullary
      disease. Pretreatment with dexamethasone as well as dual combination of PAT
      SM6/lenalidomide further increased sGRP78 expression and consecutively showed
      synergistic anti-multiple myeloma effects with PAT-SM6 in proliferation assays.
      As proof of concept, a 62-year-old male with triple resistant multiple myeloma
      treated with PAT-SM6, bortezomib, and lenalidomide experienced partial remission
      of both intra- and extramedullary lesions. CONCLUSIONS: PAT-SM6 therapy in
      combination regimens showed efficacy in relapsed-refractory multiple myeloma.
      Clin Cancer Res; 22(17); 4341-9. (c)2016 AACR.

PMID- 27029493
TI  - Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4
      Secretion in Human Cancers.
AB  - PURPOSE: Epithelial-to-mesenchymal transition (EMT) is important in cancer
      progression and metastasis. We and others have previously reported that lysyl
      oxidase (LOX) is overexpressed in aggressive cancers, is associated with
      increased mortality, and regulates EMT. However, the mechanism by which LOX
      mediates EMT is unknown. In this study, we investigated the effect of LOX on
      mediators of EMT. EXPERIMENTAL DESIGN: We used chromatin immunoprecipitation and
      promoter luciferase assays to determine the target gene of LOX. To determine the
      effects of SNAI2 in vivo, we used our metastatic anaplastic thyroid cancer (ATC)
      mouse model. To investigate the effects of LOX and SNAI2 on MMPs and TIMPs,
      protein arrays were used. Primary tumors from patients with metastatic, breast
      and colon cancer, and tissue array for thyroid cancer were assessed for SNAI2 and
      TIMP4 expression by immunohistochemistry. RESULTS: We found that LOX knockdown
      decreases SNAI2 expression in cancer cell lines. Furthermore, knockdown of LOX
      reduced SNAI2 expression in a metastatic mouse model of thyroid cancer. We also
      demonstrated that LOX binds and transactivates the SNAI2 promoter. We found a
      direct correlation in thyroid and breast cancer samples between LOX and SNAI2
      expression. To understand how LOX/SNAI2 axis mediates these effects, we performed
      a comprehensive analysis of MMPs/TIMPs. LOX and SNAI2 depletion reduced TIMP4
      secretion. Analysis of SNAI2 and TIMP4 expression showed overexpression of both
      proteins in aggressive thyroid, colon, and breast tumors. CONCLUSIONS: Our
      findings provide new evidence that LOX regulates SNAI2 expression and that SNAI2
      mediated TIMP4 secretion plays a role in cancer progression. Clin Cancer Res;
      22(17); 4491-504. (c)2016 AACR.

PMID- 27029492
TI  - Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair
      Proficient Stage II Colon Cancer.
AB  - PURPOSE: Prognostic markers that identify patients with stage II colon cancers
      who are at the risk of recurrence are essential to personalize therapy. We
      evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such
      patients. EXPERIMENTAL DESIGN: Expression of full-length GIV was evaluated by IHC
      using a newly developed mAb together with a mismatch repair (MMR)-specific
      antibody panel in three stage II colon cancer patient cohorts, that is, a
      training (n = 192), test (n = 317), and validation (n = 181) cohort, with
      clinical follow-up data. Recurrence risk stratification models were established
      in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy
      and subsequently validated. RESULTS: For T3 pMMR tumors, GIV expression and the
      presence of lymphovascular invasion (LVI) were the only factors predicting
      recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025)
      and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI:
      HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status
      classified patients into high- or low-risk groups; 3-year recurrence-free
      survival was significantly lower in the high-risk versus low-risk group across
      all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI),
      1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4%
      vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12]. CONCLUSIONS: GIV expression status
      predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk
      model combining GIV expression and LVI status information further enhances
      prediction of recurrence. Further validation studies are warranted before GIV
      status can be routinely included in patient management algorithms. Clin Cancer
      Res; 22(14); 3488-98. (c)2016 AACR.

PMID- 27029494
TI  - Cellular telephone use during free-living walking significantly reduces average
      walking speed.
AB  - BACKGROUND: Cellular telephone (cell phone) use decreases walking speed in
      controlled laboratory experiments and there is an inverse relationship between
      free-living walking speed and heart failure risk. The purpose of this study was
      to examine the impact of cell phone use on walking speed in a free-living
      environment. METHODS: Subjects (n = 1142) were randomly observed walking on a 50
      m University campus walkway. The time it took each subject to walk 50 m was
      recorded and subjects were coded into categories: cell phone held to the ear
      (talking, n = 95), holding and looking at the cell phone (texting, n = 118), not
      visibly using the cell phone (no use, n = 929). RESULTS: Subjects took
      significantly (p < 0.001) longer traversing the walkway when talking (39.3 s) and
      texting (37.9 s) versus no use (35.3 s). CONCLUSION: As was the case with the
      previous laboratory experiments, cell phone use significantly reduces average
      speed during free-living walking.

PMID- 27029495
TI  - Liver Transplantation and Donor Body Mass Index >30: Use or Refuse?
AB  - BACKGROUND: Organ shortage is a major problem in liver transplantation. The use
      of extended criteria donors has become the most important strategy for increasing
      the donor pool. However, the role of donor body mass index has not yet been
      thoroughly investigated. The aim of our study was to compare outcomes after liver
      transplantation in patients who received a liver from a donor with a BMI <30, 30
      39, and >=40, with special regard to the incidence of early allograft dysfunction
      (EAD) and primary non-function (PNF). MATERIAL AND METHODS: One hundred and sixty
      three patients who underwent liver transplantation at the University Hospital
      Aachen between June 2010 and January 2014 were included in this analysis. The
      outcome of liver transplantation was evaluated by the 30-day and 1-year patient
      and graft survival rates and the incidences of post-reperfusion syndrome (PRS),
      EAD, and PNF. RESULTS: The BMI 30-39 group had a higher incidence of EAD than the
      BMI <30 and BMI >=40 groups. We observed 5 cases of PNF in the BMI <30 group. The
      incidence of acute renal failure was significantly higher in the BMI 30-39 and
      BMI >=40 groups than in the BMI <30 group. Patient and graft survival did not
      differ significantly among the 3 groups. CONCLUSIONS: Based on the findings of
      this study, grafts from obese donors with a BMI >30 can be safely transplanted.
      Therefore, the donor pool can be enlarged to include such obese donors without a
      negative impact on the long-term patient outcome after liver transplantation.

PMID- 27029496
TI  - Individual and combined effects of noncontingent reinforcement and response
      blocking on automatically reinforced problem behavior.
AB  - Noncontingent reinforcement (NCR) and response blocking are 2 common
      interventions for problem behavior maintained by automatic reinforcement. We
      implemented NCR and blocking with 1 boy and found this combined intervention to
      be effective at decreasing high rates of automatically reinforced pica. With
      another child, we compared the effects of blocking alone to the combined
      intervention. With the third child, we compared NCR alone and blocking alone to
      the combined intervention. Results showed that the combined intervention was
      effective at reducing automatically reinforced problem behavior while moderate to
      high levels of item engagement maintained. When evaluated individually, neither
      NCR nor blocking was sufficient to reduce problem behavior to clinically
      significant levels.

PMID- 27029497
TI  - Telomere length connects melanoma and glioma predispositions.

PMID- 27029498
TI  - Contagion on complex networks with persuasion.
AB  - The threshold model has been widely adopted as a classic model for studying
      contagion processes on social networks. We consider asymmetric individual
      interactions in social networks and introduce a persuasion mechanism into the
      threshold model. Specifically, we study a combination of adoption and persuasion
      in cascading processes on complex networks. It is found that with the
      introduction of the persuasion mechanism, the system may become more vulnerable
      to global cascades, and the effects of persuasion tend to be more significant in
      heterogeneous networks than those in homogeneous networks: a comparison between
      heterogeneous and homogeneous networks shows that under weak persuasion,
      heterogeneous networks tend to be more robust against random shocks than
      homogeneous networks; whereas under strong persuasion, homogeneous networks are
      more stable. Finally, we study the effects of adoption and persuasion threshold
      heterogeneity on systemic stability. Though both heterogeneities give rise to
      global cascades, the adoption heterogeneity has an overwhelmingly stronger impact
      than the persuasion heterogeneity when the network connectivity is sufficiently
      dense. 

PMID- 27029500
TI  - Oral oxybutynin for the treatment of hyperhidrosis: outcomes after one-year
      follow-up.
AB  - BACKGROUND/OBJECTIVES: Although many treatments are available to address
      hyperhidrosis, the results are not always satisfactory. The aim of the study was
      to assess the effectiveness, optimal dosage regimen and long-term safety of oral
      oxybutynin in the treatment of hyperhidrosis. METHODS: A retrospective review was
      performed on 110 patients who underwent treatment for hyperhidrosis between
      February 2007 and December 2013. Their response to treatment was evaluated using
      the hyperhidrosis disease severity scale at baseline, 3 and 12 months.
      Additionally, the safety and effectiveness of different up-dosing and fixed-dose
      regimens were compared. RESULTS: After 3 months of treatment, 87 of the 110
      patients (79%) had responded (63%), which was considered excellent. After 12
      months, 63 patients (62%) continued to respond, and the response was considered
      excellent in 50%. Nine patients were lost to follow up between month 3 and 12. In
      total, 77 and 70% of the patients who responded at 3 and 12 months, respectively,
      reported mild adverse events. No serious adverse events were observed. Treatment
      adherence was significantly higher among patients following the individualised up
      dosing regimen. CONCLUSION: Oral oxybutynin may be an effective and safe option
      for the long-term treatment of hyperhidrosis. To improve treatment adherence,
      oxybutynin dosing regimens should be individualised on the basis of the patient's
      tolerance and response.

PMID- 27029499
TI  - Design, synthesis, crystallization and biological evaluation of new symmetrical
      biscationic compounds as selective inhibitors of human Choline Kinase alpha1
      (ChoKalpha1).
AB  - A novel family of compounds derivative of 1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1
      phenylene))bis(methylene))-bispyridinium or -bisquinolinium bromide (10a-l)
      containing a pair of oxygen atoms in the spacer of the linker between the
      biscationic moieties, were synthesized and evaluated as inhibitors of choline
      kinase against a panel of cancer-cell lines. The most promising compounds in this
      series were 1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1
      phenylene))bis(methylene))bis(4-(dimethylamino)pyridinium) bromide (10a) and 1,1'
      (((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))-bis(7-chloro-4
      (pyrrolidin-1-yl)quinolinium) bromide (10l), which inhibit human choline kinase
      (ChoKalpha1) with IC50 of 1.0 and 0.92 MUM, respectively, in a range similar to
      that of the previously reported biscationic compounds MN58b and RSM932A. Our
      compounds show greater antiproliferative activities than do the reference
      compounds, with unprecedented values of GI50 in the nanomolar range for several
      of the cancer-cell lines assayed, and more importantly they present low toxicity
      in non-tumoral cell lines, suggesting a cancer-cell-selective antiproliferative
      activity. Docking studies predict that the compounds interact with the choline
      binding site in agreement with the binding mode of most previously reported
      biscationic compounds. Moreover, the crystal structure of ChoKalpha1 with
      compound 10a reveals that this compound binds to the choline-binding site and
      mimics HC-3 binding mode as never before. 

PMID- 27029501
TI  - Selecting the right drug treatment for adults with type 2 diabetes.

PMID- 27029503
TI  - Transcatheter Aortic Valve Replacement in Bicuspid Aortic Stenosis Using Lotus
      Valve System.
AB  - Bicuspid aortic stenosis (BAS) has been excluded in clinical trials on
      transcatheter aortic valve replacement (TAVR) due to the presumed uneven
      expansion of the aortic prosthesis, leading to significant paravalvular
      regurgitation (PVR). There is no transcatheter heart valve (THV) commercially
      approved for treating BAS. The Lotus Valve System mitigates PVR by possessing an
      adaptive seal and being fully re-positionable. The latter is also important in
      preventing embolization, as the location of prosthesis fixation in BAS could be
      variable due to the presence of less expandable raphe. We report our early
      experience with the Lotus Valve System in three consecutive TAVR for BAS. They
      all provide good clinical and hemodynamic results without significant PVR. We
      conclude that the use of Lotus Valve System for treating BAS is feasible and
      safe, and may have advantages over the previous generation TAVR systems. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27029502
TI  - A non-human primate model of radiation-induced cachexia.
AB  - Cachexia, or muscle wasting, is a serious health threat to victims of
      radiological accidents or patients receiving radiotherapy. Here, we propose a non
      human primate (NHP) radiation-induced cachexia model based on clinical and
      molecular pathology findings. NHP exposed to potentially lethal partial-body
      irradiation developed symptoms of cachexia such as body weight loss in a time-
      and dose-dependent manner. Severe body weight loss as high as 20-25% was observed
      which was refractory to nutritional intervention. Radiographic imaging indicated
      that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis
      of muscle tissues showed abnormalities such as presence of central nuclei,
      inflammation, fatty replacement of skeletal muscle, and muscle fiber
      degeneration. Biochemical parameters such as hemoglobin and albumin levels
      decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and
      myostatin were significantly changed in the irradiated cachectic NHP compared to
      the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose
      radiation manifest cachexia-like symptoms in a time- and dose-dependent manner.
      This model provides a unique opportunity to study the mechanism of radiation
      induced cachexia and will aid in efficacy studies of mitigators of this disease. 

PMID- 27029504
TI  - From pole to pole: the potential for the Arctic seastar Asterias amurensis to
      invade a warming Southern Ocean.
AB  - Due to climatic warming, Asterias amurensis, a keystone boreal predatory seastar
      that has established extensive invasive populations in southern Australia, is a
      potential high-risk invader of the sub-Antarctic and Antarctic. To assess the
      potential range expansion of A. amurensis to the Southern Ocean as it warms, we
      investigated the bioclimatic envelope of the adult and larval life stages. We
      analysed the distribution of adult A. amurensis with respect to present-day and
      future climate scenarios using habitat temperature data to construct species
      distribution models (SDMs). To integrate the physiological response of the
      dispersive phase, we determined the thermal envelope of larval development to
      assess their performance in present-day and future thermal regimes and the
      potential for success of A. amurensis in poleward latitudes. The SDM indicated
      that the thermal 'niche' of the adult stage correlates with a 0-17  degrees C and
      1-22.5  degrees C range, in winter and summer, respectively. As the ocean warms,
      the range of A. amurensis in Australia will contract, while more southern
      latitudes will have conditions favourable for range expansion. Successful
      fertilization occurred from 3 to 23.8  degrees C. By day 12, development to the
      early larval stage was successful from 5.5 to 18  degrees C. Although embryos
      were able to reach the blastula stage at 2  degrees C, they had arrested
      development and high mortality. The optimal thermal range for survival of pelagic
      stages was 3.5-19.2  degrees C with a lower and upper critical limit of 2.6 and
      20.3  degrees C, respectively. Our data predict that A. amurensis faces demise in
      its current invasive range while more favourable conditions at higher latitudes
      would facilitate invasion of both larval and adult stages to the Southern Ocean.
      Our results show that vigilance is needed to reduce the risk that this
      ecologically important Arctic carnivore may invade the Southern Ocean and
      Antarctica.

PMID- 27029505
TI  - Day-restricted feeding during pregnancy and lactation programs glucose
      intolerance and impaired insulin secretion in male rat offspring.
AB  - AIM: The maternal environment during pregnancy and lactation plays a determining
      role in programming energy metabolism in offspring. Among a myriad of maternal
      factors, disruptions in the light/dark cycle during pregnancy can program glucose
      intolerance in offspring. Out-of-phase feeding has recently been reported to
      influence metabolism in adult humans and rodents; however, it is not known
      whether this environmental factor impacts offspring metabolism when applied
      during pregnancy and lactation. This study aims to determine whether maternal day
      restricted feeding (DF) influences energy metabolism in offspring. METHODS:
      Pregnant and lactating Wistar rats were subjected to ad libitum (AL) or DF during
      pregnancy and lactation. The offspring born to the AL and DF dams were intra- and
      interfostered, which resulted in 4 group types. RESULTS: The male offspring born
      to and breastfed by the DF dams (DF/DF off) were glucose intolerant, but without
      parallel insulin resistance as adults. Experiments with isolated pancreatic
      islets demonstrated that the male DF/DF off rats had reduced insulin secretion
      with no parallel disruption in calcium handling. However, this reduction in
      insulin secretion was accompanied by increased miRNA-29a and miRNA34a expression
      and decreased syntaxin 1a protein levels. CONCLUSION: We conclude that out-of
      phase feeding during pregnancy and lactation can lead to glucose intolerance in
      male offspring, which is caused by a disruption in insulin secretion capacity.
      This metabolic programming is possibly caused by mechanisms dependent on miRNA
      modulation of syntaxin 1a.

PMID- 27029506
TI  - Amino acid biosynthetic pathways as antifungal targets for fungal infections.

PMID- 27029507
TI  - Cerebrospinal fluid markers in the differentiation of molecular subtypes of
      sporadic Creutzfeldt-Jakob disease.
AB  - BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) analysis supports the clinical
      diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an
      adequate clinical context. A diagnostic potential has been attributed to CSF
      proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau)
      protein, amyloid beta1-42 , S100B and neuron-specific enolase (NSE). There has
      been only limited information available about the contribution of CSF analysis in
      the differentiation of various molecular sCJD subtypes. METHODS: The CSF levels
      of the aforementioned proteins from 73 sCJD patients with distinct molecular
      subtypes were determined. RESULTS: Differences in tau values were significant
      amongst the homozygous patients (MM and VV genotype) compared to the heterozygous
      group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels
      (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed
      in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation
      of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of
      S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype.
      PRNP codon 129 genotype, PrP(sc) isotype, disease duration and clinical stage
      influenced the test sensitivity in all proteins. CONCLUSIONS: Cerebrospinal fluid
      protein levels might be useful in the pre-mortem differentiation of molecular
      sCJD subtypes when the codon 129 genotype is known.

PMID- 27029508
TI  - Using higher-order Markov models to reveal flow-based communities in networks.
AB  - Complex systems made of interacting elements are commonly abstracted as networks,
      in which nodes are associated with dynamic state variables, whose evolution is
      driven by interactions mediated by the edges. Markov processes have been the
      prevailing paradigm to model such a network-based dynamics, for instance in the
      form of random walks or other types of diffusions. Despite the success of this
      modelling perspective for numerous applications, it represents an over
      simplification of several real-world systems. Importantly, simple Markov models
      lack memory in their dynamics, an assumption often not realistic in practice.
      Here, we explore possibilities to enrich the system description by means of
      second-order Markov models, exploiting empirical pathway information. We focus on
      the problem of community detection and show that standard network algorithms can
      be generalized in order to extract novel temporal information about the system
      under investigation. We also apply our methodology to temporal networks, where we
      can uncover communities shaped by the temporal correlations in the system.
      Finally, we discuss relations of the framework of second order Markov processes
      and the recently proposed formalism of using non-backtracking matrices for
      community detection. 

PMID- 27029509
TI  - Application of iron oxide nanoparticles in glioma imaging and therapy: from bench
      to bedside.
AB  - Gliomas are the most common primary brain tumors and have a very dismal
      prognosis. However, recent advancements in nanomedicine and nanotechnology
      provide opportunities for personalized treatment regimens to improve the poor
      prognosis of patients suffering from glioma. This comprehensive review starts
      with an outline of the current status facing glioma. It then provides an overview
      of the state-of-the-art applications of iron oxide nanoparticles (IONPs) to
      glioma diagnostics and therapeutics, including MR contrast enhancement, drug
      delivery, cell labeling and tracking, magnetic hyperthermia treatment and
      magnetic particle imaging. It also addresses current challenges associated with
      the biological barriers and IONP design with an emphasis on recent advances and
      innovative approaches for glioma targeting strategies. Opportunities for future
      development are highlighted. 

PMID- 27029510
TI  - An external portable device for adaptive deep brain stimulation (aDBS) clinical
      research in advanced Parkinson's Disease.
AB  - Compared to conventional deep brain stimulation (DBS) for patients with
      Parkinson's Disease (PD), the newer approach of adaptive DBS (aDBS), regulating
      stimulation on the basis of the patient's clinical state, promises to achieve
      better clinical outcomes, avoid adverse-effects and save time for tuning
      parameters. A remaining challenge before aDBS comes into practical use is to
      prove its feasibility and its effectiveness in larger groups of patients and in
      more ecological conditions. We developed an external portable aDBS system
      prototype designed for clinical testing in freely-moving PD patients with
      externalized DBS electrodes. From a single-channel bipolar artifact-free
      recording, it analyses local field potentials (LFPs), during ongoing DBS for
      tuning stimulation parameters, independent from the specific feedback algorithm
      implemented. We validated the aDBS system in vitro, by testing both its sensing
      and closed-loop stimulation capabilities, and then tested it in vivo, focusing on
      the sensing capabilities. By applying the aDBS system prototype in a patient with
      PD, we provided evidence that it can track levodopa and DBS-induced LFP spectral
      power changes among different patient's clinical states. Our system, intended for
      testing LFP-based feedback strategies for aDBS, should help understanding how and
      whether aDBS therapy works in PD and indicating future technical and clinical
      advances. 

PMID- 27029512
TI  - Light pollution: Assessment of sky glow on two dark sky regions of Portugal.
AB  - Artificial light at night (ALAN), producing light pollution (LP), is not a matter
      restricted to astronomy anymore. Light is part of modern societies and, as a
      consequence, the natural cycle day-night (bright-dark) has been interrupted in a
      large segment of the global population. There is increasing evidence that
      exposure to certain types of light at night and beyond threshold levels may
      produce hazardous effects to humans and the environment. The concept of "dark
      skies reserves" is a step forward in order to preserve the night sky and a means
      of enhancing public awareness of the problem of spread of light pollution
      worldwide. The aim of this study was to assess the skyglow at two sites in
      Portugal, the Peneda-Geres National Park (PNPG) and the region now known as Dark
      Sky Alqueva Reserve. The latter site was classified as a "Starlight Tourism
      Destination" by the Starlight Foundation (the first in the world to achieve this
      classification) following a series of night sky measurements in situ described
      herein. The measurements at PNPG also contributed to the new set of regulations
      concerning light pollution at this national park. This study presents the first
      in situ systematic measurements of night sky brightness, showing that at the two
      sites the skies are mostly in levels 3 to 4 of the Bortle 9-level scale (with
      level 1 being the best achievable). The results indicate that the sources of
      light pollution and skyglow can be attributed predominantly to contamination from
      nearby urban regions.

PMID- 27029511
TI  - Identification of HNF-4alpha as a key transcription factor to promote ChREBP
      expression in response to glucose.
AB  - Transcription factor carbohydrate responsive element binding protein (ChREBP)
      promotes glycolysis and lipogenesis in metabolic tissues and cancer cells. ChREBP
      alpha and ChREBP-beta, two isoforms of ChREBP transcribed from different
      promoters, are both transcriptionally induced by glucose. However, the mechanism
      by which glucose increases ChREBP mRNA levels remains unclear. Here we report
      that hepatocyte nuclear factor 4 alpha (HNF-4alpha) is a key transcription factor
      for glucose-induced ChREBP-alpha and ChREBP-beta expression. Ectopic HNF-4alpha
      expression increased ChREBP transcription while knockdown of HNF-4alpha greatly
      reduced ChREBP mRNA levels in liver cancer cells and mouse primary hepatocytes.
      HNF-4alpha not only directly bound to an E-box-containing region in intron 12 of
      the ChREBP gene, but also promoted ChREBP-beta transcription by directly binding
      to two DR1 sites and one E-box-containing site of the ChREBP-beta promoter.
      Moreover, HNF-4alpha interacted with ChREBP-alpha and synergistically promoted
      ChREBP-beta transcription. Functionally, HNF-4alpha suppression reduced glucose
      dependent ChREBP induction. Increased nuclear abundance of HNF-4alpha and its
      binding to cis-elements of ChREBP gene in response to glucose contributed to
      glucose-responsive ChREBP transcription. Taken together, our results not only
      revealed the novel mechanism by which HNF-4alpha promoted ChREBP transcription in
      response to glucose, but also demonstrated that ChREBP-alpha and HNF-4alpha
      synergistically increased ChREBP-beta transcription. 

PMID- 27029513
TI  - Nonlinear effects in evolution - an ab initio study: A model in which the
      classical theory of evolution occurs as a special case.
AB  - An ab initio approach was used to study the molecular-level interactions that
      connect gene-mutation to changes in an organism's phenotype. The study provides
      new insights into the evolutionary process and presents a simplification whereby
      changes in phenotypic properties may be studied in terms of the binding
      affinities of the chemical interactions affected by mutation, rather than by
      correlation to the genes. The study also reports the role that nonlinear effects
      play in the progression of organs, and how those effects relate to the classical
      theory of evolution. Results indicate that the classical theory of evolution
      occurs as a special case within the ab initio model - a case having two
      attributes. The first attribute: proteins and promoter regions are not shared
      among organs. The second attribute: continuous limiting behavior exists in the
      physical properties of organs as well as in the binding affinity of the
      associated chemical interactions, with respect to displacements in the chemical
      properties of proteins and promoter regions induced by mutation. Outside of the
      special case, second-order coupling contributions are significant and nonlinear
      effects play an important role, a result corroborated by analyses of published
      activity levels in binding and transactivation assays. Further, gradations in the
      state of perfection of an organ may be small or large depending on the type of
      mutation, and not necessarily closely-separated as maintained by the classical
      theory. Results also indicate that organs progress with varying degrees of
      interdependence, the likelihood of successful mutation decreases with increasing
      complexity of the affected chemical system, and differences between the ab initio
      model and the classical theory increase with increasing complexity of the
      organism.

PMID- 27029514
TI  - Discriminate protein decoys from native by using a scoring function based on
      ubiquitous Phi and Psi angles computed for all atom.
AB  - The success of solving the protein folding and structure prediction problems in
      molecular and structural biology relies on an accurate energy function. With the
      rapid advancement in the computational biology and bioinformatics fields, there
      is a growing need of solving unknown fold and structure faster and thus an
      accurate energy function is indispensable. To address this need, we develop a new
      potential function, namely 3DIGARS3.0, which is a linearly weighted combination
      of 3DIGARS, mined accessible surface area (ASA) and ubiquitously computed Phi
      (uPhi) and Psi (uPsi) energies - optimized by a Genetic Algorithm (GA). We use a
      dataset of 4332 protein-structures to generate uPhi and uPsi based score
      libraries to be used within the core 3DIGARS method. The optimized weight of each
      component is obtained by applying Genetic Algorithm based optimization on three
      challenging decoy sets. The improved 3DIGARS3.0 outperformed state-of-the-art
      methods significantly based on a set of independent test datasets.

PMID- 27029516
TI  - Determination of nitroxide spin label conformations via PELDOR and X-ray
      crystallography.
AB  - Pulsed electron-electron double resonance (PELDOR or DEER) in combination with
      site-directed spin labelling has emerged as an important method for measuring
      nanometer distance constraints that are used to obtain coarse-grained structures
      of biomolecules or to follow their conformational changes. Translating measured
      spin-spin distances between spin labels into structural information requires
      taking the conformational flexibility of spin label side chains into account.
      Here, we present an analysis of orientation selective PELDOR data recorded on six
      singly MTSSL-labelled azurin mutants. The analysis yielded conformational MTSSL
      ensembles, which are considerably narrower than those predicted using in silico
      spin labeling methods but match well with spin label conformations found in the
      corresponding crystal structures. The possible reasons and consequences for
      predicting spin label conformers in the fold of biomolecules are discussed. 

PMID- 27029515
TI  - Reconstruction and topological characterization of the sigma factor regulatory
      network of Mycobacterium tuberculosis.
AB  - Accessory sigma factors, which reprogram RNA polymerase to transcribe specific
      gene sets, activate bacterial adaptive responses to noxious environments. Here we
      reconstruct the complete sigma factor regulatory network of the human pathogen
      Mycobacterium tuberculosis by an integrated approach. The approach combines
      identification of direct regulatory interactions between M. tuberculosis sigma
      factors in an E. coli model system, validation of selected links in M.
      tuberculosis, and extensive literature review. The resulting network comprises 41
      direct interactions among all 13 sigma factors. Analysis of network topology
      reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high
      connectivity and (iii) distinct communities containing multiple sigma factors.
      These topological features are likely associated with multi-layer signal
      processing and specialized stress responses involving multiple sigma factors.
      Moreover, the identification of overrepresented network motifs, such as
      autoregulation and coregulation of sigma and anti-sigma factor pairs, provides
      structural information that is relevant for studies of network dynamics. 

PMID- 27029517
TI  - Integrated analysis of miRNAs and transcriptomes in Aedes albopictus midgut
      reveals the differential expression profiles of immune-related genes during
      dengue virus serotype-2 infection.
AB  - Mosquito microRNAs (miRNAs) are involved in host-virus interaction, and have been
      reported to be altered by dengue virus (DENV) infection in Aedes albopictus
      (Diptera: Culicidae). However, little is known about the molecular mechanisms of
      Aedes albopictus midgut-the first organ to interact with DENV-involved in its
      resistance to DENV. Here we used high-throughput sequencing to characterize miRNA
      and messenger RNA (mRNA) expression patterns in Aedes albopictus midgut in
      response to dengue virus serotype 2. A total of three miRNAs and 777 mRNAs were
      identified to be differentially expressed upon DENV infection. For the mRNAs, we
      identified 198 immune-related genes and 31 of them were differentially expressed.
      Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses
      also showed that the differentially expressed immune-related genes were involved
      in immune response. Then the differential expression patterns of six immune
      related genes and three miRNAs were confirmed by real-time reverse transcription
      polymerase chain reaction. Furthermore, seven known miRNA-mRNA interaction pairs
      were identified by aligning our two datasets. These analyses of miRNA and mRNA
      transcriptomes provide valuable information for uncovering the DENV response
      genes and provide a basis for future study of the resistance mechanisms in Aedes
      albopictus midgut. 

PMID- 27029518
TI  - Using global sensitivity analysis of demographic models for ecological impact
      assessment.
AB  - Population viability analysis (PVA) is widely used to assess population-level
      impacts of environmental changes on species. When combined with sensitivity
      analysis, PVA yields insights into the effects of parameter and model structure
      uncertainty. This helps researchers prioritize efforts for further data
      collection so that model improvements are efficient and helps managers prioritize
      conservation and management actions. Usually, sensitivity is analyzed by varying
      one input parameter at a time and observing the influence that variation has over
      model outcomes. This approach does not account for interactions among parameters.
      Global sensitivity analysis (GSA) overcomes this limitation by varying several
      model inputs simultaneously. Then, regression techniques allow measuring the
      importance of input-parameter uncertainties. In many conservation applications,
      the goal of demographic modeling is to assess how different scenarios of impact
      or management cause changes in a population. This is challenging because the
      uncertainty of input-parameter values can be confounded with the effect of
      impacts and management actions. We developed a GSA method that separates model
      outcome uncertainty resulting from parameter uncertainty from that resulting from
      projected ecological impacts or simulated management actions, effectively
      separating the 2 main questions that sensitivity analysis asks. We applied this
      method to assess the effects of predicted sea-level rise on Snowy Plover
      (Charadrius nivosus). A relatively small number of replicate models
      (approximately 100) resulted in consistent measures of variable importance when
      not trying to separate the effects of ecological impacts from parameter
      uncertainty. However, many more replicate models (approximately 500) were
      required to separate these effects. These differences are important to consider
      when using demographic models to estimate ecological impacts of management
      actions.

PMID- 27029519
TI  - HLA-C*07:486, a novel HLA-C*07 variant, detected in a Taiwanese individual.
AB  - One nucleotide exchange at residue 812 of the HLA-C*07:02:01:01 results in a
      novel allele, HLA-C*07:486. 

PMID- 27029520
TI  - [The importance of nutrition counselling in veterinary practice].
AB  - OBJECTIVE: Collection of epidemiological data about the importance of nutrition
      counselling and current nutritional knowledge of veterinary surgeons. MATERIAL
      AND METHODS: A total of 707 veterinarians were interviewed based on a
      standardized questionnaire. The survey was divided into three sections and
      comprised the topics person and working environment, level of education and
      current knowledge regarding nutrition, as well as the significance of nutrition
      in daily practice. RESULTS: The majority of respondents (91.3%) worked in a
      practice with up to four veterinarians, where most of the participants (89.3%)
      treated up to 50 patients daily. On a scale from 1 to 5, the veterinarians
      evaluated their knowledge with a mean of 2.59 (+/- 0.798) and the importance of
      nutrition with a mean of 2.02 (+/- 0.818). Nutrition consulting was provided for
      at least half of the patients by 37.3% of the participants. The counselling was
      performed in different ways. The main reasons for a lack of consultancy despite a
      current indication were time and labor (37.1%) as well as the low willingness of
      customers to pay (34.6%). The majority of veterinarians were interested in
      further training concerning nutrition counselling. CONCLUSION: Nutrition
      consulting is an important part of daily veterinary practice but there is a
      demand for further training. CLINICAL RELEVANCE: Although the importance of
      nutrition is clear, only some of the veterinary surgeons perform consulting on a
      regular basis. In particular, in case of an existing indication, a nutrition
      consulting is advisable to ensure maximum success of treatment.

PMID- 27029521
TI  - Polymer-brush lubrication: a review of recent theoretical advances.
AB  - This review compiles recent theoretical advances to describe compressive and
      shear forces of polymer-brush bilayers, which consist of two opposing brushes in
      contact. Such model systems for polymer-brush lubrication are frequently used as
      a benchmark to gain insight into biological problems, e.g., synovial joint
      lubrication. Based on scaling theory, I derive conformational and collective
      properties of polymer-brush bilayers in equilibrium and out-of-equilibrium
      situations, such as shear forces in the linear and nonlinear response regimes of
      stationary shear and under non-stationary shear. Furthermore, I discuss the
      influence of macromolecular inclusions and electrostatic interactions on polymer
      brush lubrication. Comparisons to alternative analytical approaches, experiments
      and numerical results are performed. Special emphasis is given to methods for
      simulating polymer-brush bilayers using molecular dynamics simulations. 

PMID- 27029522
TI  - Towards a new paradigm: Activity level balanced sustainability reporting.
AB  - Technoeconomic paradigms based economic growth theories suggest that waves of
      technological innovations drove the economic growth of advanced economies.
      Widespread economic degradation and pollution is an unintended consequence of
      such growth. Tackling environmental and social issues at firm levels would help
      us to overcome such issues at macro-levels. Consequently, the Triple Bottom Line
      (TBL) reporting approach promotes firm level economic, environmental and social
      performances. Incorporating Zink's (2014) 3-pillar presentation model, this paper
      indicates that economic, social and environmental performances tend to be
      reported at firm level. All three pillars are not covered evenly at the activity
      levels. Thus, a loophole is identified whereby excellent environmental
      performance at activity levels could potentially leave poor social performance
      undisclosed. A refinement of the TBL paradigm, whereby all three pillars are
      covered at the activity level, is suggested, to enhance sustainability reporting.

PMID- 27029523
TI  - Diverticular disease and additional comorbidities associated with increased risk
      of dementia.
AB  - BACKGROUND AND AIM: Colonic diverticular disease may cause a chronic systemic
      effect, but its role in the development of dementia remains unclear. The purpose
      of this study was to investigate the potential increased risk for dementia in
      colonic diverticular disease. METHODS: We conducted a population-based cohort
      study using data from Taiwan's National Health Insurance Research Database. A
      total of 66 377 sex-matched, age-matched, and index year-matched (1:4) pairs of
      patients with colonic diverticular disease and 265 508 patients without colonic
      diverticular disease, who served as controls, were selected from all potential
      participants aged 20 years or older in the database. Each subject was
      individually tracked from 2000 to 2011 to identify incident cases of dementia.
      Cox proportional hazards regression was employed to calculate the hazard ratios
      and 95% confidence intervals for the association between colonic diverticular
      disease and dementia. RESULTS: There were 1057 dementia cases in the diverticular
      disease cohort during the follow-up period of 315 171 person-years; the overall
      incidence rate of dementia differed from that of the control group (3.35 vs 2.43
      per 1000 person-years, P < 0.001). The adjusted hazard ratio for dementia was
      1.24 (95% confidence interval 1.15-1.33) for diverticular disease patients after
      adjusting for age, sex, and comorbidities. CONCLUSIONS: Colonic diverticular
      disease may be associated with increased risk for dementia.

PMID- 27029525
TI  - Cancer tolerance, resistance, pathogenicity and virulence: deconstructing the
      disease state.
AB  - Immunologists have recently taken note of the fact that a host not only resists
      infection, but also exhibits a capacity to manage the pathology associated with
      such infection - a concept referred to as tolerance. Here we explore how the
      tolerance/resistance (T/R) framework can be implemented within an oncological
      context and explore a number of implications. In particular, the T/R framework
      distinguishes between pathology manifesting from extensive tumor burden, versus
      cancers intrinsically expressing a more pathogenic phenotype. Consequently, the
      T/R framework provides novel methodology in studying the nature of cancer
      pathology and for marker identification. Additionally, this framework may aid in
      redefining the therapeutic end point under suitable circumstances: establishing
      cancer as a chronic, manageable disease. 

PMID- 27029524
TI  - Two-photon excited photoconversion of cyanine-based dyes.
AB  - The advent of phototransformable fluorescent proteins has led to significant
      advances in optical imaging, including the unambiguous tracking of cells over
      large spatiotemporal scales. However, these proteins typically require activating
      light in the UV-blue spectrum, which limits their in vivo applicability due to
      poor light penetration and associated phototoxicity on cells and tissue. We
      report that cyanine-based, organic dyes can be efficiently photoconverted by
      nonlinear excitation at the near infrared (NIR) window. Photoconversion likely
      involves singlet-oxygen mediated photochemical cleavage, yielding blue-shifted
      fluorescent products. Using SYTO62, a biocompatible and cell-permeable dye, we
      demonstrate photoconversion in a variety of cell lines, including depth-resolved
      labeling of cells in 3D culture. Two-photon photoconversion of cyanine-based dyes
      offer several advantages over existing photoconvertible proteins, including use
      of minimally toxic NIR light, labeling without need for genetic intervention,
      rapid kinetics, remote subsurface targeting, and long persistence of
      photoconverted signal. These findings are expected to be useful for applications
      involving rapid labeling of cells deep in tissue. 

PMID- 27029526
TI  - Investigation of Y/SBA Composite Molecular Sieves Morphology Control and
      Catalytic Performance for n-Pentane Aromatization.
AB  - Using Y molecular sieve as the core, Y/SBA-15 composite molecular sieves were
      prepared by different crystallization methods in the paper. The growth process
      and morphologies of the composite molecular sieves were controlled by adjusting
      the synthesis factors. The structures and acidity of two kinds of composite
      molecular sieves were characterized by X-ray diffraction (XRD), N2
      adsorption/desorption, transmission electron microscopy (TEM), and NH3-TPD. The
      catalysis performances of the composite molecular sieves were investigated in the
      aromatization reaction of n-pentane. The results indicated that the desired core
      shell composite molecular sieves were obtained when the crystallization
      conditions were 36 hours, 100  degrees C and secondary crystallization. The
      aromatization results showed that core-shell composite molecular sieves had
      better selectivity for producing high application value xylenes compared to mixed
      crystal composite molecular sieves. 

PMID- 27029527
TI  - The autoimmunity-associated gene RGS1 affects the frequency of T follicular
      helper cells.
AB  - RGS1 (regulator of G-protein signaling 1) has been associated with multiple
      autoimmune disorders including type I diabetes. RGS1 desensitizes the chemokine
      receptors CCR7 and CXCR4 that are critical to the localization of T and B cells
      in lymphoid organs. To explore how RGS1 variation contributes to autoimmunity, we
      generated Rgs1 knockdown (KD) mice in the nonobese diabetic (NOD) model for type
      I diabetes. We found that Rgs1 KD increased the size of germinal centers, but
      decreased the frequency of T follicular helper (TFH) cells. We show that loss of
      Rgs1 in T cells had both a T cell-intrinsic effect on migration and TFH cell
      frequency, and an indirect effect on B-cell migration and germinal center
      formation. Notably, several recent publications described an increase in
      circulating TFH cells in patients with type I diabetes, suggesting this cell
      population is involved in pathogenesis. Though Rgs1 KD was insufficient to alter
      diabetes frequency in the NOD model, our findings raise the possibility that RGS1
      plays a role in autoimmunity owing to its function in TFH cells. This mechanistic
      link, although speculative at this time, would lend support to the notion that
      TFH cells are key participants in autoimmunity and could explain the association
      of RGS1 with several immune-mediated diseases.

PMID- 27029528
TI  - Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression
      of cancer and non-transformed cells.
AB  - Progression of cell cycle is associated with changes in K(+) channel expression
      and activity. In this study, we report that Kv10.1, a K(+) channel that increases
      cell proliferation and tumor growth, is regulated at the transcriptional level by
      the pRb/E2F1 pathway. De-repression of E2F1 by HPV-E7 oncoprotein leads to
      increased expression of Kv10.1. In proliferating cells, E2F1 transcription factor
      binds directly to the Kv10.1 promoter during (or close to) G2/M, resulting in
      transient expression of the channel. Importantly, this happens not only in cancer
      cells but also in non-transformed cells. Lack of Kv10.1 in both cancer and non
      transformed cells resulted in prolonged G2/M phase, as indicated by
      phosphorylation of Cdk1 (Y15) and sustained pRb hyperphosphorylation. Our results
      strongly suggest that Kv10.1 expression is coupled to cell cycle progression and
      facilitates G2/M progression in both healthy and tumor cells. 

PMID- 27029529
TI  - Andrographolide inhibits prostate cancer by targeting cell cycle regulators,
      CXCR3 and CXCR7 chemokine receptors.
AB  - Despite state of the art cancer diagnostics and therapies offered in clinic,
      prostate cancer (PCa) remains the second leading cause of cancer-related deaths.
      Hence, more robust therapeutic/preventive regimes are required to combat this
      lethal disease. In the current study, we have tested the efficacy of
      Andrographolide (AG), a bioactive diterpenoid isolated from Andrographis
      paniculata, against PCa. This natural agent selectively affects PCa cell
      viability in a dose and time-dependent manner, without affecting primary prostate
      epithelial cells. Furthermore, AG showed differential effect on cell cycle phases
      in LNCaP, C4-2b and PC3 cells compared to retinoblastoma protein (RB(-/-)) and
      CDKN2A lacking DU-145 cells. G2/M transition was blocked in LNCaP, C4-2b and PC3
      after AG treatment whereas DU-145 cells failed to transit G1/S phase. This
      difference was primarily due to differential activation of cell cycle regulators
      in these cell lines. Levels of cyclin A2 after AG treatment increased in all PCa
      cells line. Cyclin B1 levels increased in LNCaP and PC3, decreased in C4-2b and
      showed no difference in DU-145 cells after AG treatment. AG decreased cyclin E2
      levels only in PC3 and DU-145 cells. It also altered Rb, H3, Wee1 and CDC2
      phosphorylation in PCa cells. Intriguingly, AG reduced cell viability and the
      ability of PCa cells to migrate via modulating CXCL11 and CXCR3 and CXCR7
      expression. The significant impact of AG on cellular and molecular processes
      involved in PCa progression suggests its potential use as a therapeutic and/or
      preventive agent for PCa. 

PMID- 27029531
TI  - Erratum.

PMID- 27029530
TI  - B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells.
AB  - Preeclampsia is one of the leading causes of maternal and perinatal mortality and
      morbidity and its pathogenesis is not fully understood. B-cell lymphoma 6 (BCL6),
      a key regulator of B-lymphocyte development, is altered in preeclamptic
      placentas. We show here that BCL6 is present in all 3 studied trophoblast cell
      lines and it is predominantly expressed in trophoblastic HTR-8/SVneo cells
      derived from a 1(st) trimester placenta, suggestive of its involvement in
      trophoblast expansion in the early stage of placental development. BCL6 is
      strongly stabilized upon stress stimulation. Inhibition of BCL6, by
      administrating either small interfering RNA or a specific small molecule
      inhibitor 79-6, reduces proliferation and induces apoptosis in trophoblastic
      cells. Intriguingly, depletion of BCL6 in HTR-8/SVneo cells results in a mitotic
      arrest associated with mitotic defects in centrosome integrity, indicative of its
      involvement in mitotic progression. Thus, like in haematopoietic cells and breast
      cancer cells, BCL6 promotes proliferation and facilitates survival of
      trophoblasts under stress situation. Further studies are required to decipher its
      molecular roles in differentiation, migration and the fusion process of
      trophoblasts. Whether increased BCL6 observed in preeclamptic placentas is one of
      the causes or the consequences of preeclampsia warrants further investigations in
      vivo and in vitro. 

PMID- 27029532
TI  - Analysis of the Asymmetric Synergy in the Adsorption of Zwitterionic-Ionic
      Surfactant Mixtures at the Air-Water Interface below and above the Critical
      Micelle Concentration.
AB  - Surface tension (ST) and neutron reflection (NR) measurements have been made on a
      series of mixtures of two ionic surfactants, one anionic (SDS) and one cationic
      (C12TAB), with the two zwitterionic surfactants dodecyldimethylammonium
      propanesulfonate (C12SB) and dodecyldimethylammonium acetate C12CB. The anionic
      surfactant SDS interacts equally strongly with both zwitterionics and the C12TAB
      less strongly. For the SDS-C12SB mixtures simultaneous fitting of ST and NR data
      made it possible to use the pseudophase approximation with an expansion of the
      excess free energy, GE, up to and including the quartic term. GE is asymmetric
      for the adsorbed layer and the minimum occurs at a surface mole fraction, xSDS,
      of 0.38 with a depth of -2.8RT. NR was also used to follow the adsorption above
      the CMC, and the changes showed that the intramicellar interaction is more
      asymmetric, but weaker than the surface interaction with a depth of GE of -2.2RT
      at the minimum of xSDS = 0.23. A strong synergy in the total surface excess was
      observed above the mixed CMC with an enhancement over the adsorption of the pure
      components of about 45%, which appears to result from a sharp variation of the
      packing with surface composition coupled with the effects of the strongly
      asymmetric micellization. NR data on SDS-C12CB showed that GE for both surface
      and micelles was similarly asymmetric to those for SDS-C12SB, but there is no
      strong synergy in adsorption. This is attributed to the more rigid headgroup.
      C12TAB-C12SB has an asymmetric GE for both surface and micelle similar to those
      for SDS-C12SB but the depths are smaller at -0.6RT and -0.5RT, respectively, and
      there is no synergy in the total adsorption.

PMID- 27029534
TI  - Chamomile decoction extract inhibits human neutrophils ROS production and
      attenuates alcohol-induced haematological parameters changes and erythrocytes
      oxidative stress in rat.
AB  - BACKGROUND: The aim of this study was to evaluate the protective effects of
      subacute pre-treatment with chamomile (Matricaria recutita L.) decoction extract
      (CDE) against stimulated neutrophils ROS production as well as ethanol (EtOH)
      induced haematological changes and erythrocytes oxidative stress in rat. METHODS:
      Neutrophils were isolated and ROS generation was measured by luminol-amplified
      chemiluminescence. Superoxide anion generation was detected by the cytochrome c
      reduction assay. Adult male wistar rats were used and divided into six groups of
      ten each: control, EtOH, EtOH + various doses of CDE (25, 50, and 100 mg/kg,
      b.w.), and EtOH+ ascorbic acid (AA). Animals were pre-treated with CDE extract
      during 10 days. RESULTS: We found that CDE inhibited (P <= 0.0003) luminol
      amplified chemiluminescence of resting neutrophils and N-formyl methionylleucyl
      phenylalanine (fMLF) or phorbolmyristate acetate (PMA) stimulated neutrophils, in
      a dose-dependent manner. CDE had no effect on superoxide anion, but it inhibited
      (P <= 0.0004) H2O2 production in cell free system. In vivo, CDE counteracted (P
      <= 0.0034) the effect of single EtOH administration which induced (P < 0.0001) an
      increase of white blood cells (WBC) and platelets (PLT) counts. Our results also
      demonstrated that alcohol administration significantly (P < 0.0001) induced
      erythrocytes lipoperoxidation increase and depletion of sulfhydryl groups (-SH)
      content as well as antioxidant enzyme activities as superoxide dismutase (SOD),
      catalase (CAT), and glutathione peroxidase (GPx). More importantly, we found that
      acute alcohol administration increased (P < 0.0001) erythrocytes and plasma
      hydrogen peroxide (H2O2), free iron, and calcium levels while the CDE pre
      treatment reversed increased (P <= 0.0051) all these intracellular disturbances.
      CONCLUSIONS: These findings suggest that CDE inhibits neutrophil ROS production
      and protects against EtOH-induced haematologiacal parameters changes and
      erythrocytes oxidative stress. The haematoprotection offered by chamomile might
      involve in part its antioxidant properties as well as its opposite effect on some
      intracellular mediators such as H2O2, free iron, and calcium.

PMID- 27029535
TI  - Analysis of vaccination campaign effectiveness and population immunity to support
      and sustain polio elimination in Nigeria.
AB  - BACKGROUND: The world is closer than ever to a polio-free Africa. In this end
      stage, it is important to ensure high levels of population immunity to prevent
      polio outbreaks. Here, we introduce a new method of assessing vaccination
      campaign effectiveness and estimating immunity at the district-level. We
      demonstrate how this approach can be used to plan the vaccination campaigns
      prospectively to better manage population immunity in Northern Nigeria. METHODS:
      Using Nigerian acute flaccid paralysis surveillance data from 2004-2014, we
      developed a Bayesian hierarchical model of campaign effectiveness and compared it
      to lot-quality assurance sampling data. We then used reconstructed sero-specific
      population immunity based on campaign history and compared district estimates of
      immunity to the occurrence of confirmed poliovirus cases. RESULTS: Estimated
      campaign effectiveness has improved across northern Nigeria since 2004, with Kano
      state experiencing an increase of 40 % (95 % CI, 26-54 %) in effectiveness from
      2013 to 2014. Immunity to type 1 poliovirus has increased steadily. On the other
      hand, type 2 immunity was low and variable until the recent use of trivalent oral
      polio vaccine. We find that immunity estimates are related to the occurrence of
      both wild and vaccine-derived poliovirus cases and that campaign effectiveness
      correlates with direct measurements using lot-quality assurance sampling. Future
      campaign schedules highlight the trade-offs involved with using different vaccine
      types. CONCLUSIONS: The model in this study provides a novel method for assessing
      vaccination campaign performance and epidemiologically-relevant estimates of
      population immunity. Small-area estimates of campaign effectiveness can then be
      used to evaluate prospective campaign plans. This modeling approach could be
      applied to other countries as well as other vaccine preventable diseases.

PMID- 27029536
TI  - Implementation of the trigger review method in Scottish general practices:
      patient safety outcomes and potential for quality improvement.
AB  - OBJECTIVES: To report the implementation of a trigger review method (TRM) in
      primary care, with a particular focus on its impact on patient safety-related
      findings. DESIGN: Cross-sectional structured review of random samples (n=25) of
      electronic records of 'high-risk' patient groups conducted twice per year (each
      for a retrospective review period of 3 months). SETTING: 274 general practices in
      two regions of Scotland. INTERVENTION: Contractual incentivisation of TRM
      implementation. MAIN OUTCOME MEASURES: Practice participation rate;
      characteristics of patient safety incidents (PSIs), for example, their
      prevalence, type, perceived severity and preventability; and actions or intended
      actions undertaken during and after trigger reviews. RESULTS: 274 of 318 eligible
      practices (86.2%) returned 536 TRM Summary Reports, which outlined findings from
      reviews of 13 351 electronic patient records. 1887 (14.1%) PSIs were recorded,
      with a mean of 3.5 (536/1887) per Summary Report (SD+/-1.6). Of these, 830
      (44.0%) were judged to have caused mild to moderate harm, with 262 (13.9%) cases
      resulting in more severe harm. A total of 852 PSIs (46.2%) were rated as
      preventable or potentially preventable. In 459 Summary Reports (85.6%), reviewers
      indicated implementing one or more improvement actions during the actual TRM
      process; and 2177 actions after completion of the TRM process (mean 4.1 (SD+/
      3.3) actions per review). CONCLUSIONS: The great majority of clinician reviewers
      'successfully' applied the TRM, uncovering important but previously undetected
      PSIs, which prompted care teams to take action during and after the trigger
      reviews. The method and data generated have the potential to drive improvements
      in related care processes at the practice, regional and national health system
      level. TRM arguably increased 'ownership' of the safety challenge and clinician
      engagement in implementing their solutions to specific problems identified. Our
      results suggest that the TRM has potential as a feasible, pragmatic approach to
      improving primary care safety and quality.

PMID- 27029537
TI  - Microbial eukaryote plankton communities of high-mountain lakes from three
      continents exhibit strong biogeographic patterns.
AB  - Microbial eukaryotes hold a key role in aquatic ecosystem functioning. Yet, their
      diversity in freshwater lakes, particularly in high-mountain lakes, is relatively
      unknown compared with the marine environment. Low nutrient availability, low
      water temperature and high ultraviolet radiation make most high-mountain lakes
      extremely challenging habitats for life and require specific molecular and
      physiological adaptations. We therefore expected that these ecosystems support a
      plankton diversity that differs notably from other freshwater lakes. In addition,
      we hypothesized that the communities under study exhibit geographic structuring.
      Our rationale was that geographic dispersal of small-sized eukaryotes in high
      mountain lakes over continental distances seems difficult. We analysed
      hypervariable V4 fragments of the SSU rRNA gene to compare the genetic microbial
      eukaryote diversity in high-mountain lakes located in the European Alps, the
      Chilean Altiplano and the Ethiopian Bale Mountains. Microbial eukaryotes were not
      globally distributed corroborating patterns found for bacteria, multicellular
      animals and plants. Instead, the plankton community composition emerged as a
      highly specific fingerprint of a geographic region even on higher taxonomic
      levels. The intraregional heterogeneity of the investigated lakes was mirrored in
      shifts in microbial eukaryote community structure, which, however, was much less
      pronounced compared with interregional beta-diversity. Statistical analyses
      revealed that on a regional scale, environmental factors are strong predictors
      for plankton community structures in high-mountain lakes. While on long-distance
      scales (>10 000 km), isolation by distance is the most plausible scenario, on
      intermediate scales (up to 6000 km), both contemporary environmental factors and
      historical contingencies interact to shift plankton community structures.

PMID- 27029538
TI  - Research and Practice Communications Between Oral Health Providers and Prenatal
      Health Providers: A Bibliometric Analysis.
AB  - Objectives We aimed to examine scholarly collaboration between oral health and
      prenatal providers. Oral disease is a silent epidemic with significant public
      health implications for pregnant women. Evidence linking poor oral health during
      pregnancy to adverse pregnancy and birth outcomes requires oral health and
      prenatal providers to communicate on the prevention, treatment and co-management
      matters pertaining to oral health issues among their pregnant patients. The need
      for inter-professional collaboration is highlighted by guidelines co-endorsed by
      the American College of Obstetricians and Gynecologists and the American Dental
      Association, stressing the importance of oral health care during pregnancy.
      Methods To assess if interdisciplinary communication occurs between oral health
      and prenatal disciplines, we conducted a network analysis of research on
      pregnancy-related periodontal disease. Results Social Network analysis allowed us
      to identify communication patterns between communities of oral health and
      prenatal professionals via scientific journals. Analysis of networks of citations
      linking journals in different fields reveals a core-periphery pattern dominated
      by oral health journals with some participation from medicine journals. However,
      an analysis of dyadic ties of citation reveals statistically significant
      "inbreeding" tendencies in the citation patterns: both medical and oral health
      journals tend to cite their own kind at greater-than-chance levels. Conclusions
      Despite evidence suggesting that professional collaboration benefits patients'
      overall health, findings from this research imply that little collaboration
      occurs between these two professional groups. More collaboration may be useful in
      addressing women's oral-systemic health concerns that result in adverse pregnancy
      outcomes.

PMID- 27029539
TI  - Developmental Origins, Epigenetics, and Equity: Moving Upstream.
AB  - The Developmental Origins of Health and Disease and the related science of
      epigenetics redefines the meaning of what constitutes upstream approaches to
      significant social and public health problems. An increasingly frequent concept
      being expressed is "When it comes to your health, your zip code may be more
      important than your genetic code". Epigenetics explains how the environment-our
      zip code-literally gets under our skin, creates biological changes that increase
      our vulnerability for disease, and even children's prospects for social success,
      over their life course and into future generations. This science requires us to
      rethink where disease comes from and the best way to promote health. It
      identifies the most fundamental social equity issue in our society: that initial
      social and biological disadvantage, established even prior to birth, and linked
      to the social experience of prior generations, is made worse by adverse
      environments throughout the life course. But at the same time, it provides hope
      because it tells us that a concerted focus on using public policy to improve our
      social, physical, and economic environments can ultimately change our biology and
      the trajectory of health and social success into future generations. 

PMID- 27029540
TI  - Impact of Missing Data for Body Mass Index in an Epidemiologic Study.
AB  - Objective To assess the potential impact of missing data on body mass index (BMI)
      on the association between prepregnancy obesity and specific birth defects.
      Methods Data from the National Birth Defects Prevention Study (NBDPS) were
      analyzed. We assessed the factors associated with missing BMI data among mothers
      of infants without birth defects. Four analytic methods were then used to assess
      the impact of missing BMI data on the association between maternal prepregnancy
      obesity and three birth defects; spina bifida, gastroschisis, and cleft lip
      with/without cleft palate. The analytic methods were: (1) complete case analysis;
      (2) assignment of missing values to either obese or normal BMI; (3) multiple
      imputation; and (4) probabilistic sensitivity analysis. Logistic regression was
      used to estimate crude and adjusted odds ratios (aOR) and 95 % confidence
      intervals (CI). Results Of NBDPS control mothers 4.6 % were missing BMI data, and
      most of the missing values were attributable to missing height (~90 %). Missing
      BMI data was associated with birth outside of the US (aOR 8.6; 95 % CI 5.5,
      13.4), interview in Spanish (aOR 2.4; 95 % CI 1.8, 3.2), Hispanic ethnicity (aOR
      2.0; 95 % CI 1.2, 3.4), and <12 years education (aOR 2.3; 95 % CI 1.7, 3.1).
      Overall the results of the multiple imputation and probabilistic sensitivity
      analysis were similar to the complete case analysis. Conclusions Although in some
      scenarios missing BMI data can bias the magnitude of association, it does not
      appear likely to have impacted conclusions from a traditional complete case
      analysis of these data.

PMID- 27029541
TI  - Dynamic posterior stabilization for degenerative lumbar spine disease: a large
      consecutive case series with long-term follow-up by additional postal survey.
AB  - INTRODUCTION: Dynamic stabilization of the degenerated spine was invented to
      overcome the negative side effects of fusion surgery like adjacent segment
      degeneration. Amongst various different implants DSS((r)) is a pedicle-based
      dynamic device for stabilizing the spine and preserving motion. Nearly no
      clinical data of the implant have been reported so far. The current analysis
      presents results from a single spine surgeon who has been using DSS((r)) for the
      past 5 years and recorded all treatment and outcome data in the international
      Spine Tango registry. MATERIALS/METHODS: From the prospectively documented
      overall patient pool 436 cases treated with DSS((r)) could be identified. The
      analysis was enhanced with a mailing of COMI patient questionnaires for
      generating longer-term follow-ups up to 4 years. RESULTS: 387 patients (189 male,
      198 female; mean age 67.3 years) with degenerative lumbar spinal disease
      including degenerative spondylolisthesis (6.1 %) could be evaluated. The type of
      degeneration was mainly spinal stenosis (89.9 %). After a mean follow-up of 1.94
      years, the COMI score and NRS back and leg pain improved significantly and to a
      clinically relevant extent. The postoperative trend analysis could not determine
      a relevant deterioration of these outcomes until 4 years postoperative. 10
      patients were revised (2.6 %) and the implant was removed; in most cases, a
      fusion was performed. Another 5 cases (1.3 %) had an extension of the dynamic
      stabilization system to the adjacent level. 84.2 % of patients rated that the
      surgery had helped a lot or had helped. DISCUSSION: The results of this large
      consecutive series with a follow-up up to 4 years could demonstrate a good and
      stable clinical outcome after posterior dynamic stabilization with DSS((r)). For
      degenerative diseases of the lumbar spine, this treatment seems to be a valid
      alternative to fusion surgery.

PMID- 27029542
TI  - Comparison of clinical efficacy and safety among three surgical approaches for
      the treatment of spinal tuberculosis: a meta-analysis.
AB  - PURPOSE: We aimed to provide evidence for clinical choice of surgical approach in
      treating spinal tuberculosis, including anterior, posterior and combined
      approaches (combined anterior and posterior approach). METHODS: A literature
      search up to June 2015 was performed on PubMed, Embase, Cochrane library, CNKI,
      Wanfang and Weipu database. Weighted mean differences (WMDs) or risk radios (RRs)
      and their 95 % confidence intervals (CI) were calculated. RESULTS: Total 26
      studies with 2345 spinal tuberculosis adults were analyzed. Results showed
      advantages of posterior approach compared with anterior approach in operation
      time (WMD = 20.91; 95 % CI: 9.05-32.76), blood loss (WMD = 72.32, 95 % CI: 13.87
      130.78), correction of angle (WMD = -2.47; 95 % CI: -4.04 to -0.90) and
      complications (RR = 1.78; 95 % CI: 1.21-2.60), and compared with combined
      approach in operation time (WMD = -82.76; 95 % CI: -94.38 to -71.14), blood loss
      (WMD = -263.63; 95 % CI: -336.85 to -190.41), hospital stay [(WMD = -4.60; 95 %
      CI: -5.10 to -4.10) and complications (RR = 0.36; 95 % CI: 0.23-0.58]. Meanwhile,
      significantly larger correction of angle (WMD = -2.25; 95 % CI: -4.35 to -0.14; P
      = 0.04) and less loss of correction (WMD = 3.97; 95 % CI: 2.22-5.72) were found
      when compared combined approach with anterior approach. However, combined
      approach had significantly longer operation time (WMD = -41.92; 95 % CI: -52.45
      to -31.38) and more blood loss (WMD = -102.18; 95 % CI: -160.45 to -43.91) than
      anterior approach. CONCLUSION: Posterior approach has better clinical outcomes
      than anterior or combined approach for spinal tuberculosis. However, individual
      assessment of each case should be considered in the clinical application of these
      surgical approaches.

PMID- 27029543
TI  - Identifying Careless Responding With the Psychopathic Personality Inventory
      Revised Validity Scales.
AB  - The Psychopathic Personality Inventory-Revised (PPI-R) includes validity scales
      that assess Deviant Responding (DR), Virtuous Responding, and Inconsistent
      Responding. We examined the utility of these scales for identifying careless
      responding using data from two online studies that examined correlates of
      psychopathy in college students (Sample 1: N = 583; Sample 2: N = 454). Compared
      with those below the cut scores, those above the cut on the DR scale yielded
      consistently lower validity coefficients when PPI-R scores were correlated with
      corresponding scales from the Triarchic Psychopathy Measure. The other three PPI
      R validity scales yielded weaker and less consistent results. Participants who
      completed the studies in an inordinately brief amount of time scored
      significantly higher on the DR and Virtuous Responding scales than other
      participants. Based on the findings from the current studies, researchers
      collecting PPI-R data online should consider identifying and perhaps screening
      out respondents with elevated scores on the DR scale.

PMID- 27029544
TI  - Preparation and Evaluation of a Zirconia/Oligosiloxane Nanocomposite for LED
      Encapsulation.
AB  - A zirconia/oligosiloxane nanocomposite encapsulant has been developed and tested
      in a high-power LED package against commercial silicone resins. The composite was
      a marriage of zirconia nanocrystals modified with butyric acid (BA) and 3
      methacryloxy propyl trimethoxysilane (MPTMS) and a high-index methacryloxy
      oligosiloxanes resin made from MPTMS plus dimethyl, diphenyl, and triphenyl
      silanes. The modified zirconia had an index of 1.762 (@589 nm) and was
      dispersible in many solvents. The oligosiloxane resin, however, had an index of
      1.5413 with good encapsulation properties and low viscosity allowing the
      incorporation of more zirconia. The final nanocomposite showed a refractive index
      of 1.625 with high transparency and a wavelength-independent scattering, both
      desirable for the light extraction from LED. When tested in a high-power LED
      package, the composite encapsulant resulted in 13% more light output compared to
      the commercial encapsulant (OE-6630, Dow Corning Corp.) and showed longer than
      1000 h of lifetime (L70) under the steady-state Temperature Humidity Bias (THB)
      test. 

PMID- 27029545
TI  - Vitamin D status among indigenous Mayan (Kekchi) and Afro-Caribe (Garifuna)
      adolescents from Guatemala: a comparative description between two ethnic groups
      residing on the Rio Dulce at the Caribbean coast in Izabal Province, Guatemala.
AB  - OBJECTIVE: To assess vitamin D status and the influence of risk factors such as
      skin pigmentation and time spent outdoors on hypovitaminosis D among Guatemalan
      Kekchi and Garifuna adolescents. DESIGN: Cross-sectional study, with convenient
      sampling design. Blood samples, anthropometric and behavioural data were all
      collected during the dry season. Serum 25-hydroxyvitamin D (25(OH)D)
      concentrations were measured by RIA. SETTING: Communities of Rio Dulce and
      Livingston, Izabal Province, Caribbean coast of Guatemala, with latitude and
      longitude of 15 degrees 49'N and 88 degrees 45'W for Livingston and 15 degrees
      46'N and 88 degrees 49'W for Rio Dulce, respectively. SUBJECTS: Eighty-six
      adolescents, divided evenly by sex and ethnicity, with mean age of 14 years.
      RESULTS: Mean (sd) 25(OH)D value was 27.8 (7.2) ng/ml for the total group, with
      25.8 (5.9) and 29.8 (7.9) ng/ml, respectively, in Kekchis and Garifunas (P=0.01).
      Use of vitamin D supplementation, clothing practices and sun protection were not
      statistically different between groups. Skin area exposed on the day of data
      collection ranged from 20.0 % minimum to 49.4 % maximum, with mean (sd) exposure
      of 32.0 (8.5) %. With univariate regression analysis, age (P=0.034), sex
      (P=0.044), ethnicity (P=0.010), time spent outdoors (P=0.006) and percentage skin
      area exposed (P=0.001) were predictive. However, multivariate analysis indicated
      that only sex (P=0.034) and percentage skin area exposed (P=0.044) remained as
      predictors of 25(OH)D. CONCLUSIONS: Despite residing in an optimal geographic
      location for sunlight exposure, nearly 65 % of study adolescents were either
      insufficient or deficient in vitamin D. Correction and long-term prevention of
      this nutritional problem may be instrumental in avoiding adverse effects in
      adulthood attributed to low 25(OH)D during adolescence.

PMID- 27029546
TI  - Comparing systemic therapy and cognitive behavioral therapy for social anxiety
      disorders: study protocol for a randomized controlled pilot trial.
AB  - BACKGROUND: Social anxiety disorders are among the most prevalent anxiety
      disorders in the general population. The efficacy of cognitive behavioral therapy
      (CBT) for social anxiety disorders is well demonstrated. However, only three
      studies point to the efficacy of systemic therapy (ST) in anxiety disorders, and
      only two of them especially focus on social anxiety disorders. These ST studies
      either do not use a good comparator but minimal supportive therapy, they do not
      use a multi-person ST but a combined therapy, or they do not especially focus on
      social anxiety disorders but mood and anxiety disorders in general. Though ST was
      approved as evidence based in Germany for a variety of disorders in 2008,
      evidence did not include anxiety disorders. This is the first pilot study that
      will investigate multi-person ST, integrating a broad range of systemic methods,
      specifically for social anxiety disorders and that will compare ST to the "gold
      standard" CBT. DESIGN: This article describes the rationale and protocol of a
      prospective, open, interventive, balanced, bi-centric, pilot randomized
      controlled trial (RCT). A total of 32 patients with a primary SCID diagnosis of
      social anxiety disorder will be randomized to either CBT or ST. Both treatments
      will be manualized. The primary outcome will include social anxiety symptoms at
      the end of therapy. Therapy will be restricted to no more than 26 hours (primary
      endpoint). Secondary outcomes will include psychological, social systems and
      interpersonal functioning, symptom adjustment, and caregiver burden, in addition
      to change measures, therapist variables and treatment adherence. At the secondary
      endpoints, 9 and 12 months after the beginning of therapy, we will again assess
      all outcomes. DISCUSSION: The study is expected to pilot test a RCT which will be
      the first to directly compare CBT and multi-person ST, integrating a broad range
      of systemic methods, for social anxiety disorders, and it will provide empirical
      evidence for the calculation of the number of patients needed for a confirmatory
      RCT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02360033 ; date of registration:
      21 January 2015.

PMID- 27029547
TI  - Diabetes treatments and risk of amputation, blindness, severe kidney failure,
      hyperglycaemia, and hypoglycaemia: open cohort study in primary care.
AB  - OBJECTIVE: To assess the risks of amputation, blindness, severe kidney failure,
      hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated
      with prescribed diabetes drugs, particularly newer agents including gliptins or
      glitazones (thiazolidinediones). DESIGN: Open cohort study in primary care.
      SETTING: 1243 practices contributing data to the QResearch database in England.
      PARTICIPANTS: 469,688 patients with type 2 diabetes aged 25-84 years between 1
      April 2007 and 31 January 2015. EXPOSURES: Hypoglycaemic agents (glitazones,
      gliptins, metformin, sulphonylureas, insulin, and other) alone and in
      combination. MAIN OUTCOME MEASURES: First recorded diagnoses of amputation,
      blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on
      patients' primary care, mortality, or hospital records. Cox models estimated
      hazard ratios for diabetes treatments adjusting for potential confounders.
      RESULTS: 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for
      glitazones and gliptins during follow-up, respectively. Compared with non-use,
      glitazones were associated with a decreased risk of blindness (adjusted hazard
      ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person
      years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37;
      65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86,
      0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin
      monotherapy or glitazones monotherapy were relatively low, there were
      significantly increased risks of severe kidney failure compared with metformin
      monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74).
      We found significantly lower risks of hyperglycaemia among patients prescribed
      dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or
      glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients
      prescribed triple therapy with metformin, sulphonylureas, and either gliptins
      (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones
      (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those
      prescribed metformin monotherapy, but these risks were similar to those involving
      dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients
      prescribed triple therapy with metformin, sulphonylureas, and glitazones had a
      significantly reduced risk of blindness compared with metformin monotherapy
      (0.67, 0.48 to 0.94). CONCLUSIONS: We have found lower risks of hyperglycaemia
      among patients prescribed dual therapy involving metformin with either gliptins
      or glitazones compared with metformin alone. Compared with metformin monotherapy,
      triple therapy with metformin, sulphonylureas, and either gliptins or glitazones
      was associated with an increased risk of hypoglycaemia, which was similar to the
      risk for dual therapy with metformin and sulphonylureas. Compared with metformin
      monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was
      associated with a reduced risk of blindness. These results, while subject to
      residual confounding, could have implications for the prescribing of
      hypoglycaemic drugs.

PMID- 27029548
TI  - The Cementocyte-An Osteocyte Relative?
AB  - Cementum is a mineralized tissue covering the tooth root that functions in tooth
      attachment and posteruptive adjustment of tooth position. During formation of the
      apically located cellular cementum, some cementoblasts become embedded in the
      cementoid matrix and become cementocytes. As apparently terminally differentiated
      cells embedded in a mineralized extracellular matrix, cementocytes are part of a
      select group of specialized cells, also including osteocytes, hypertrophic
      chondrocytes, and odontoblasts. The differentiation and potential function(s) of
      cementocytes are virtually unknown, and the question may be posed whether the
      cementocyte is a dynamic actor in cementum in comparable fashion with the
      osteocyte in the skeleton, responding to changing tooth functions and endocrine
      signals and actively directing local cementum metabolism. This review summarizes
      the literature with regard to cementocytes, comparing them to their closest
      "cousins," the osteocytes, where insights gained from osteocyte studies serve to
      inform the critical examination of cementocytes. The review identifies important
      unanswered questions about these cells regarding their origins, differentiation,
      morphology and lacuno-canalicular system, selective markers, and potential
      functions.

PMID- 27029549
TI  - Do little interactions get lost in dark random forests?
AB  - BACKGROUND: Random forests have often been claimed to uncover interaction
      effects. However, if and how interaction effects can be differentiated from
      marginal effects remains unclear. In extensive simulation studies, we investigate
      whether random forest variable importance measures capture or detect gene-gene
      interactions. With capturing interactions, we define the ability to identify a
      variable that acts through an interaction with another one, while detection is
      the ability to identify an interaction effect as such. RESULTS: Of the single
      importance measures, the Gini importance captured interaction effects in most of
      the simulated scenarios, however, they were masked by marginal effects in other
      variables. With the permutation importance, the proportion of captured
      interactions was lower in all cases. Pairwise importance measures performed about
      equal, with a slight advantage for the joint variable importance method. However,
      the overall fraction of detected interactions was low. In almost all scenarios
      the detection fraction in a model with only marginal effects was larger than in a
      model with an interaction effect only. CONCLUSIONS: Random forests are generally
      capable of capturing gene-gene interactions, but current variable importance
      measures are unable to detect them as interactions. In most of the cases,
      interactions are masked by marginal effects and interactions cannot be
      differentiated from marginal effects. Consequently, caution is warranted when
      claiming that random forests uncover interactions.

PMID- 27029550
TI  - Perchlorate and Diet: Human Exposures, Risks, and Mitigation Strategies.
AB  - Perchlorate is an endocrine-disrupting chemical that interferes with the normal
      functioning of the thyroid gland. Maternal thyroid dysfunction during gestation
      may alter fetal brain development. Perchlorate contamination is widespread: it is
      present in the body of all Americans tested and the majority of foods tested. The
      main sources of food contamination appear to be hypochlorite bleach, a
      disinfectant and sanitizer, that when poorly managed quickly degrades to
      perchlorate and perchlorate-laden plastic food packaging for dry food or
      localized contamination from manufacturing or processing of the chemical.
      Eliminating perchlorate from food packaging and improving bleach management, such
      as reducing concentration and storage time and temperature, would result in
      reduced perchlorate contamination of food and water. 

PMID- 27029551
TI  - Reliable classification of facial phenotypic variation in craniofacial
      microsomia: a comparison of physical exam and photographs.
AB  - BACKGROUND: Craniofacial microsomia is a common congenital condition for which
      children receive longitudinal, multidisciplinary team care. However, little is
      known about the etiology of craniofacial microsomia and few outcome studies have
      been published. In order to facilitate large, multicenter studies in craniofacial
      microsomia, we assessed the reliability of phenotypic classification based on
      photographs by comparison with direct physical examination. METHODS: Thirty-nine
      children with craniofacial microsomia underwent a physical examination and
      photographs according to a standardized protocol. Three clinicians completed
      ratings during the physical examination and, at least a month later, using
      respective photographs for each participant. We used descriptive statistics for
      participant characteristics and intraclass correlation coefficients (ICCs) to
      assess reliability. RESULTS: The agreement between ratings on photographs and
      physical exam was greater than 80 % for all 15 categories included in the
      analysis. The ICC estimates were higher than 0.6 for most features. Features with
      the highest ICC included: presence of epibulbar dermoids, ear abnormalities, and
      colobomas (ICC 0.85, 0.81, and 0.80, respectively). Orbital size, presence of
      pits, tongue abnormalities, and strabismus had the lowest ICC, values (0.17 or
      less). There was not a strong tendency for either type of rating, physical exam
      or photograph, to be more likely to designate a feature as abnormal. The
      agreement between photographs and physical exam regarding the presence of a prior
      surgery was greater than 90 % for most features. CONCLUSIONS: Our results suggest
      that categorization of facial phenotype in children with CFM based on photographs
      is reliable relative to physical examination for most facial features.

PMID- 27029552
TI  - CYP1A2--a novel genetic marker for early aromatase inhibitor response in the
      treatment of breast cancer patients.
AB  - BACKGROUND: Endocrine resistance is a major obstacle to optimal treatment effect
      in breast cancer. Some genetic markers have been proposed to predict response to
      aromatase inhibitors (AIs) but the data is insufficient. The aim of the study was
      to find new genetic treatment predictive markers of AIs. METHODS: The ongoing
      population-based BC-blood study in Lund, Sweden includes women with primary
      breast cancer. This paper is based on AI-treated patients with estrogen receptor
      positive tumors who underwent breast cancer surgery in 2002-2008. First, an
      exploratory analysis of 1931 SNPs in 227 genes involved in absorption,
      distribution, metabolism, and elimination of multiple medications, using DMETTM
      chips, was conducted in a subset of the cohort with last follow-up in December
      31st 2011 (13 cases, 11 controls). Second, selected SNPs from the first analysis
      were re-analyzed concerning risk for early breast cancer events in the extended
      cohort of 201 AI-treated with last follow-up in June 30th 2014. Clinical data
      were obtained from medical records and population registries. RESULTS: Only
      CYP1A2 rs762551 C-allele was significantly associated with increased risk for
      early events in the 24 patients (P = 0.0007) and in the extended cohort, adjusted
      Hazard ratio (HR) 2.22 (95% CI 1.03-4.80). However, the main prognostic impact
      was found within five years, adjusted HR 7.88 (95% CI 2.13-29.19). The impact of
      the CYP1A2 rs762551 C-allele was modified by a functional polymorphism in the
      regulator gene AhR Arg554Lys (G > A). Compared to patients who were homozygous
      for the major allele in both genes (CYP1A2 A/A and AhR G/G), a 9-fold risk for
      early events was found in patients who had at least one minor allele in both
      genes, adjusted HR 8.95 (95% CI 2.55-31.35), whereas patients with at least one
      minor allele in either but not both genes had a 3-fold risk for early events,
      adjusted HR 2.81 (95% CI 1.07-7.33). The impact of CYP1A2 rs762551 C-allele was
      also modified by the CYP19A1 rs4646 C/C, adjusted HR 3.39 (95% CI 1.60-7.16) for
      this combination. This association was strongest within the first five years,
      adjusted HR 10.42 (95% CI 3.45-31.51). CONCLUSION: CYP1A2 rs762551 was identified
      as a new potential predictive marker for early breast cancer events in AI-treated
      breast cancer patients. Moreover, combined genotypes of CYP1A2 rs762551 and
      CYP19A1 rs4646 or AhR Arg554Lys could further improve prediction of early AI
      treatment response. If confirmed, these results may provide a way to more
      personalized medicine.

PMID- 27029553
TI  - The effects of total knee replacement and non-surgical treatment on pain
      sensitization and clinical pain.
AB  - BACKGROUND: The objective was to compare the effect of total knee replacement
      (TKR) followed by a 3-month non-surgical treatment with the non-surgical
      treatment alone in reducing pain sensitization and other pain-related measures in
      patients with knee osteoarthritis. METHODS: One hundred patients were randomized
      to (1) TKR followed by a non-surgical treatment of neuromuscular exercise,
      education, diet, insoles and pain medication or (2) the non-surgical treatment
      alone. Outcomes assessed at baseline and after 3 months were as follows: (1) pain
      sensitization assessed as pressure-pain thresholds (PPTs) at the knee (localized
      sensitization) and the lower leg (spreading sensitization), (2) peak pain
      intensity during the previous 24 h, (3) pain intensity after 30 min of walking,
      (4) pain location and pattern, (5) spreading of pain on a region-divided body
      chart and (6) the usage of pain medication. RESULTS: There was a statistical
      significant mean difference (95% CI) in change in PPTs from baseline to 3 months
      between groups in the crude analysis of 71 kPa (21-121) and of 75 kPa (33-117)
      when adjusting for baseline PPT, age, gender and body mass index, favouring the
      group having TKR. There were no significant between-group differences in change
      in the pain-related measures from baseline to 3 months (p = 0.15-0.27). Both
      groups improved in most of the pain-related measures (p < 0.05). CONCLUSIONS: At
      3 months, TKR followed by non-surgical treatment is more effective in reducing
      localized and spreading pain sensitization than non-surgical treatment alone.
      Both treatments are equally efficacious in reducing the pain-related measures of
      this study. WHAT DOES THIS STUDY ADD?: Knee replacement followed by non-surgical
      treatment is more effective in reducing pain sensitization, but not other pain
      related measures, as compared to non-surgical treatment alone at 3 months.

PMID- 27029554
TI  - Genome-based microbial ecology of anammox granules in a full-scale wastewater
      treatment system.
AB  - Partial-nitritation anammox (PNA) is a novel wastewater treatment procedure for
      energy-efficient ammonium removal. Here we use genome-resolved metagenomics to
      build a genome-based ecological model of the microbial community in a full-scale
      PNA reactor. Sludge from the bioreactor examined here is used to seed reactors in
      wastewater treatment plants around the world; however, the role of most of its
      microbial community in ammonium removal remains unknown. Our analysis yielded 23
      near-complete draft genomes that together represent the majority of the microbial
      community. We assign these genomes to distinct anaerobic and aerobic microbial
      communities. In the aerobic community, nitrifying organisms and heterotrophs
      predominate. In the anaerobic community, widespread potential for partial
      denitrification suggests a nitrite loop increases treatment efficiency. Of our
      genomes, 19 have no previously cultivated or sequenced close relatives and six
      belong to bacterial phyla without any cultivated members, including the most
      complete Omnitrophica (formerly OP3) genome to date. 

PMID- 27029555
TI  - Zebrafish biosensor for toxicant induced muscle hyperactivity.
AB  - Robust and sensitive detection systems are a crucial asset for risk management of
      chemicals, which are produced in increasing number and diversity. To establish an
      in vivo biosensor system with quantitative readout for potential toxicant effects
      on motor function, we generated a transgenic zebrafish line TgBAC(hspb11:GFP)
      which expresses a GFP reporter under the control of regulatory elements of the
      small heat shock protein hspb11. Spatiotemporal hspb11 transgene expression in
      the musculature and the notochord matched closely that of endogenous hspb11
      expression. Exposure to substances that interfere with motor function induced a
      dose-dependent increase of GFP intensity beginning at sub-micromolar
      concentrations, while washout of the chemicals reduced the level of hspb11
      transgene expression. Simultaneously, these toxicants induced muscle
      hyperactivity with increased calcium spike height and frequency. The hspb11
      transgene up-regulation induced by either chemicals or heat shock was eliminated
      after co-application of the anaesthetic MS-222. TgBAC(hspb11:GFP) zebrafish
      embryos provide a quantitative measure of muscle hyperactivity and represent a
      robust whole organism system for detecting chemicals that affect motor function. 

PMID- 27029556
TI  - Putative digenic inheritance of heterozygous RP1L1 and C2orf71 null mutations in
      syndromic retinal dystrophy.
AB  - BACKGROUND: Retinitis pigmentosa (RP) is the most common cause of inherited
      retinal degeneration and can occur in non-syndromic and syndromic forms.
      Syndromic RP is accompanied by other symptoms such as intellectual disability,
      hearing loss, or congenital abnormalities. Both forms are known to exhibit
      complex genetic interactions that can modulate the penetrance and expressivity of
      the phenotype. MATERIALS AND METHODS: In an individual with atypical RP, hearing
      loss, ataxia and cerebellar atrophy, whole exome sequencing was performed. The
      candidate pathogenic variants were tested by developing an in vivo zebrafish
      model and assaying for retinal and cerebellar integrity. RESULTS: Exome
      sequencing revealed a complex heterozygous protein-truncating mutation in RP1L1,
      p.[(Lys111Glnfs*27; Gln2373*)], and a heterozygous nonsense mutation in C2orf71,
      p.(Ser512*). Mutations in both genes have previously been implicated in autosomal
      recessive non-syndromic RP, raising the possibility of a digenic model in this
      family. Functional testing in a zebrafish model for two key phenotypes of the
      affected person showed that the combinatorial suppression of rp1l1 and c2orf71l
      induced discrete pathology in terms of reduction of eye size with concomitant
      loss of rhodopsin in the photoreceptors, and disorganization of the cerebellum.
      CONCLUSIONS: We propose that the combination of heterozygous loss-of-function
      mutations in these genes drives syndromic retinal dystrophy, likely through the
      genetic interaction of at least two loci. Haploinsufficiency at each of these
      loci is insufficient to induce overt pathology.

PMID- 27029557
TI  - Tick tock: time for a change?
AB  - Issue addressed: New developments in front-of-pack nutrition labelling are
      substantially improving the nutrition information available at the point of
      purchase. This has led to a need to reconsider the role of health logos such as
      the National Heart Foundation's 'Tick'.Methods: Using a qualitative, exploratory
      approach involving 10 focus groups with adults and children, this study
      investigated consumers' attitudes to the Tick and its relevance to their purchase
      decisions.Results: Both adults and children exhibited awareness of the Tick and
      its aim to indicate healthier product alternatives. Views on the effectiveness of
      the Tick were polarised, with some considering it a useful tool and others
      querying the basis of its licensing arrangements.Conclusions: While the Tick has
      in the past played a role in assisting consumers to make more informed decisions
      and encouraging favourable modification of the food supply, recent questions
      relating to its role and credibility have resulted in the Heart Foundation
      deciding to retire it.So what?: After a quarter of a century in the Australian
      marketplace, the National Heart Foundation's Tick program has been reviewed. The
      findings of the present study provide insight into consumers' views of the Tick
      and suggest that the emergence of more comprehensive food labelling initiatives
      may make logo-based nutrition labels redundant.

PMID- 27029559
TI  - Degeneration of an injured spinothalamic tract in a patient with mild traumatic
      brain injury.
AB  - OBJECTIVES: This study reports on a patient who developed degeneration of an
      injured spinothalamic tract (STT) detected on diffusion tensor tractography (DTT)
      following mild traumatic brain injury (TBI). CASE DESCRIPTION: A 56-year-old
      female had suffered from head trauma resulting from a pedestrian car accident.
      The patient did not experience loss of consciousness or post-traumatic amnesia
      and the patient's Glasgow Coma Scale score was 15. She had begun to feel pain in
      her left hand and foot at ~ 7 days after onset. The characteristics and severity
      of pain were as follows: constant tingling and pricking sensation without
      allodynia or hyperalgesia (Visual Analogue Scale score: 3~4). No specific focal
      lesion was observed on brain and spine MRI and an electromyography study showed
      no evidence of peripheral nerve injury or radiculopathy. At 6 months after onset,
      the central pain in the left hand and foot became aggravated, with a Visual
      Analogue Scale score of 6. RESULTS: On 1-month DTT, partial tearing was observed
      in both STTs. In contrast, both partially torn STTs had become atrophy on 9-month
      DTT. CONCLUSIONS: This study recommends further studies conducted on the
      prognosis (regeneration or degeneration) of injured STTs and on the effect of
      change of an injured STT on central pain.

PMID- 27029558
TI  - Connecting the innate and adaptive immune responses in mouse choroidal
      neovascularization via the anaphylatoxin C5a and gammadeltaT-cells.
AB  - Neovascular age-related macular degeneration (AMD) is characterized by choroidal
      neovascularization (CNV). An overactive complement system is associated with AMD
      pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated
      in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells.
      In murine CNV, infiltrating gammadeltaT- rather than Th17-cells produce the IL-17
      measurable in lesioned eyes. Here we asked whether C5a generated locally in
      response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were
      generated using laser photocoagulation and quantified by imaging; T-lymphocytes
      were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17
      producing gammadeltaT- and Th17-cells; yet in the CNV eye, only elevated levels
      of gammadeltaT-cells were observed. Systemic administration of anti-C5- or anti
      C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and
      gammadeltaT-cells, reduced CNV size and eliminated ocular gammadeltaT-cell
      infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory
      state; and splenocyte proliferation was elevated in response to ocular proteins.
      Thus, we demonstrated that CNV lesions trigger a systemic immune response,
      augmenting local ocular inflammation via the infiltration of IL-17-producing
      gammadeltaT-cells, which are presumably recruited to the eye in a C5a-dependent
      manner. Understanding the complexity of complement-mediated pathological
      mechanisms will aid in the development of an AMD treatment. 

PMID- 27029560
TI  - Reno- and splenoportal anastomosis for a retransplant patient with situs
      inversus.
AB  - PV thrombosis following pediatric LT is a serious complication that may lead to
      graft loss. LDLT poses limitations with regard to the availability of vein grafts
      for complex PV reconstructions. We herein report a unique reconstruction of the
      PV inflow in a one-yr-old boy with situs inversus undergoing re-LDLT. The inflow
      was derived from the SPV and the RRV. A common channel was created utilizing a
      donor IMV and the recipient explant LHV as vascular conduits. With the
      application of innovative surgical reconstructions, pre-existing portomesenteric
      thrombosis may be amenable to re-LDLT in the pediatric population.

PMID- 27029561
TI  - Preparation and Sonodynamic Antitumor Effect of Protohemin-Conjugated Multiwalled
      Carbon Nanotubes Functionalized with Carboxylic Group.
AB  - Preclinical Research Sonodynamic therapy (SDT) is a cutting edge approach to
      treating cancer that involves necrosis and/or apoptosis. Multiwalled carbon
      nanotubes functionalized with carboxylic groups (MWCNTs-COOH) due their
      physicochemical structure represent a novel drug delivery system in the field of
      nanomedicine. The purpose of the research reported in this paper was to increase
      the antitumor potency and reduce the potential side effects of protohemin (Ph), a
      sonosensitizer for SDT, which was noncovalently encapsulated into MWCNTs-COOH
      (MWCNTs-Ph). The Ph loading efficiency in MWCNTs-COOH carrier was determined as
      approximately 68.8% (w/w). The growth inhibition rate of MWCNTs-Ph (Ph: 180
      MUg/mL) was approximately 95 +/- 8.5%, whereas Ph-F (Ph: 180 MUg/mL) inhibited 58
      +/- 4.5% of tumor cell. Ph (Ph: 180 MUg/mL) alone had no antitumor effect in HepG
      2 cells using ultrasound treatment at 1.0 MHz and 0.5 W/cm(2) for 100 s.
      Assessment of the antitumor effects of MWCNTs-Ph and Ph-F at day 11 after SDT
      showed that he tumor inhibition ratio for MWCNTs-Ph (6.18 * 10(-2) g.kg(-1) .d(
      1) ) was 82.8%, twice that of Ph-F (6.18 * 10(-2) g.kg(-1) .d(-1) ) ay 41.8%. In
      conclusion, MWCNTs-Ph had increased antitumor efficiency and also decreased
      potential side effects. Drug Dev Res 77 : 152-158, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27029562
TI  - Palladium-catalyzed cross-coupling of enamides with sterically hindered alpha
      bromocarbonyls.
AB  - Palladium-catalyzed intermolecular alkylation of enamides with alpha-bromo
      carbonyls was developed. Under mild reaction conditions, various cyclic and
      acyclic enamides reacted well with alpha-bromo carbonyls to afford the
      corresponding multi-substituted alkene products in good yields. The coupling
      products could be converted into very useful gamma-amino acid, delta-amino
      alcohol, 1,4-dicarbonyl and gamma-lactam derivatives. 

PMID- 27029563
TI  - Looking for hotspots of marine metacommunity connectivity: a methodological
      framework.
AB  - Seascape connectivity critically affects the spatiotemporal dynamics of marine
      metacommunities. Understanding how connectivity patterns emerge from physically
      and biologically-mediated interactions is therefore crucial to conserve marine
      ecosystem functions and biodiversity. Here, we develop a set of biophysical
      models to explore connectivity in assemblages of species belonging to a typical
      Mediterranean community (Posidonia oceanica meadows) and characterized by
      different dispersing traits. We propose a novel methodological framework to
      synthesize species-specific results into a set of community connectivity metrics
      and show that spatiotemporal variation in magnitude and direction of the
      connections, as well as interspecific differences in dispersing traits, are key
      factors structuring community connectivity. We eventually demonstrate how these
      metrics can be used to characterize the functional role of each marine area in
      determining patterns of community connectivity at the basin level and to support
      marine conservation planning. 

PMID- 27029564
TI  - Inhibition of GSK-3beta Alleviates Collagen II-Induced Rheumatoid Arthritis in
      Rats.
AB  - BACKGROUND: Glycogen synthase kinase-3beta (GSK-3beta) inhibitor is a
      serine/threonine kinase with an inhibitory role in glycogen synthesis, which is
      essential in inflammatory and immunological diseases. The purpose of our study
      was to determine if TDZD-8 can alleviate collagen II-induced rheumatoid arthritis
      in rats. MATERIAL/METHODS: Twenty collagen II-induced rheumatoid arthritis rats
      were treated with selective GSK-3beta inhibitor. The effects of GSK-3beta
      inhibition on collagen II-induced rheumatoid arthritis in the rats were evaluated
      by paw edema, histological examination of arthritic synovium, radiographic
      examination of knee joint, and the level of inflammation mediators such as
      prostaglandin E2, 5-hydroxytryptamin, and histamine. The level of cytokines such
      as IL-6, IL-12, IL-10, and TNF-alpha, was examined by Elisa. RESULTS: GSK-3beta
      inhibitor significantly reduced the development of rheumatoid arthritis in rats.
      The levels of inflammation mediators such as prostaglandin E2, 5
      hydroxytryptamin, and histamine were decreased in the TDZD-8 group. Serum levels
      of IL-6, IL-12, and TNF-alpha were significantly reduced in the TDZD-8 group
      compared with the RA group. CONCLUSIONS: Treatment with GSK-3beta inhibitor
      suppressed inflammatory response in RA rats. These findings suggest that the
      inhibition of GSK-3beta can be an effective treatment for RA.

PMID- 27029565
TI  - Adhesion of Shewanella oneidensis MR-1 to Goethite: A Two-Dimensional Correlation
      Spectroscopic Study.
AB  - Bacterial adhesion to mineral surfaces is an important but underappreciated
      process. To decipher the molecular level process and mechanism, the adhesion of
      Shewanella oneidensis MR-1 cells to goethite was investigated using flow-cell
      attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy
      coupled with two-dimensional correlation spectroscopy (2D-COS) analysis. The FTIR
      results indicate that bacterial phosphate-moieties play an important role in the
      formation of mono- and bidentate inner-sphere complexes, whereas carboxylic
      groups on cell surface only have a minor contribution to its adhesion. The 2D-COS
      analysis in short-term (0-120 min) and long-term (2-18 h) stages reveal that the
      adhesion process was in the following sequence: change in H-bonds of proteins on
      cell surfaces > formation of monodentate inner-sphere surface complexes >
      formation of outer-sphere surface complexes > transformation of protein secondary
      structure on cell surfaces > formation of additional bridging bidentate surface
      complexes. In addition, the adhesion of MR-1 cells on goethite was pH dependent
      due to pH impacts on the cell structure and the interface charge. The in situ ATR
      FTIR integrated with 2D-COS analysis highlights its great potential in exploring
      complex surface reactions with microbes involved. These results improve our
      understanding of microbe-mineral interactions at the molecular level and have
      significant implications for a series of biogeochemical processes.

PMID- 27029566
TI  - Uncommon cutaneous lymphoproliferative disorders in two patients with rheumatoid
      arthritis.
AB  - Two patients with rheumatoid arthritis developed rare cutaneous lymphomas while
      on long-term immunosuppression: extranodal NK/T-cell lymphoma, nasal and
      plasmablastic lymphoma. We give an overview of these lymphomas in the context of
      rheumatoid arthritis and postulate whether these diagnoses could be
      iatrogenically induced.

PMID- 27029567
TI  - Magnetic resonance imaging findings of cellular angiofibroma of the tunica
      vaginalis of the testis: a case report.
AB  - BACKGROUND: Cellular angiofibroma represents a rare mesenchymal tumor typically
      involving the inguinoscrotal area in middle-aged men. Although the origin of this
      benign tumor is unknown, it is histologically classified as an angiomyxoid tumor.
      Cellular angiofibroma is characterized by a diversity of pathological and imaging
      features. An accurate preoperative diagnosis is challenging. Magnetic resonance
      imaging examination of the scrotum has been reported as a valuable adjunct
      modality in the investigation of scrotal pathology. The technique by providing
      both structural and functional information is useful in the differentiation
      between extratesticular and intratesticular diseases and in the preoperative
      characterization of the histologic nature of various scrotal lesions. There are
      few reports in the English literature addressing the magnetic resonance imaging
      findings of cellular angiofibroma of the scrotum and no reports on functional
      magnetic resonance imaging data. Here we present the first case of a cellular
      angiofibroma arising from the tunica vaginalis of the testis and we discuss the
      value of a multiparametric magnetic resonance protocol, including diffusion
      weighted imaging, magnetization transfer imaging and dynamic contrast-enhanced
      magnetic resonance imaging in the preoperative diagnosis of this rare neoplasm.
      CASE PRESENTATION: A 47-year Greek man presented with a painless left scrotal
      swelling, which had gradually enlarged during the last 6 months. Magnetic
      resonance imaging of his scrotum displayed a left paratesticular mass, in close
      proximity to the tunica vaginalis, with heterogeneous high signal intensity on T2
      weighted images and no areas of restricted diffusion. The tumor was hypointense
      on magnetization transfer images, suggestive for the presence of macromolecules.
      On dynamic contrast-enhanced magnetic resonance imaging the mass showed intense
      heterogeneous enhancement with a type II curve. Magnetic resonance imaging
      findings were strongly suggestive of a benign paratesticular tumor, which was
      confirmed on pathology following lesion excision. CONCLUSIONS: Magnetic resonance
      imaging of the scrotum by combining conventional and functional magnetic
      resonance data provides useful diagnostic information in the preoperative
      characterization of scrotal masses. A possible diagnosis of a benign
      paratesticular tumor based on magnetic resonance imaging features may improve
      patient care and decrease the number of unnecessary radical surgical
      explorations.

PMID- 27029568
TI  - miR-186 in Alzheimer's disease: a big hope for a small RNA?

PMID- 27029569
TI  - Stopping cells from dividing.

PMID- 27029570
TI  - Tuning the photo-response in monolayer MoS2 by plasmonic nano-antenna.
AB  - Monolayer molybdenum disulfide (MoS2) has recently attracted intense interests
      due to its remarkable optical properties of valley-selected optical response,
      strong nonlinear wave mixing and photocurrent/photovoltaic generation and many
      corresponding potential applications. However, the nature of atomic-thin
      thickness of monolayer MoS2 leads to inefficient light-matter interactions and
      thereby hinders its optoelectronic applications. Here we report on the enhanced
      and controllable photo-response in MoS2 by utilizing surface plasmonic resonance
      based on metallic nano-antenna with characteristic lateral size of 40 * 80 nm.
      Our nano-antenna is designed to have one plasmonic resonance in the visible range
      and can enhance the MoS2 photoluminescence intensity up to 10 folds. The
      intensity enhancement can be effectively tuned simply by the manipulation of
      incident light polarization. In addition, we can also control the oscillator
      strength ratio between exciton and trion states by controlling polarization
      dependent hot carrier doping in MoS2. Our results demonstrate the possibility in
      controlling the photo-response in broad two-dimensional materials by well
      designed nano-antenna and facilitate its coming optoelectronic applications. 

PMID- 27029571
TI  - Efficacy of a balloon-expandable vascular access system in transfemoral TAVI
      patients.
AB  - BACKGROUND: Vascular complications (VC) are a serious and frequent complication
      of transfemoral transcatheter aortic valve implantation (TAVI) and result in
      increased morbidity and mortality. It has been suggested that newly developed
      vascular sheaths may increase the ability to perform transfemoral TAVI in
      patients with normal and access-limiting peripheral artery disease (PAD) and
      reduce vascular complications. AIMS: We sought to assess the safety and efficacy
      of the 19 French (F) SoloPath balloon-expandable transfemoral vascular access
      system in patients who underwent transfemoral TAVI at our center between 2011 and
      2014. METHODS AND RESULTS: Single-center retrospective study of 90 patients who
      underwent transfemoral TAVI with the use of the SoloPath sheath. Patients were
      categorized into two groups according to a sheath to femoral artery ratio (SFAR)
      of less than or equal to 1.05, or greater than 1.05. Overall, the incidence of
      major bleeding complications was low, 4.4%. No significant differences were found
      in technical or procedural success rates (100% in both groups and 100% vs. 91.3;
      P = 0.09; respectively), total vascular complications (20.8 vs. 21.7; P = 0.92)
      or total bleeding complications (20.8 vs. 30.4; P = 0.36 between those with SFAR
      greater or less than 1.05. CONCLUSIONS: The use of the SoloPath balloon
      expandable sheath is feasible and safe even in patients with SFAR > 1.05, showing
      no increased vascular or bleeding complications compared to patients with larger
      vascular access. (c) 2016 Wiley Periodicals, Inc.

PMID- 27029572
TI  - Benthic algae compensate for phytoplankton losses in large aquatic ecosystems.
AB  - Anthropogenic activities can induce major trophic shifts in aquatic systems, yet
      we have an incomplete understanding of the implication of such shifts on
      ecosystem function and on primary production (PP) in particular. In recent
      decades, phytoplankton biomass and production in the Laurentian Great Lakes have
      declined in response to reduced nutrient concentrations and invasive mussels.
      However, the increases in water clarity associated with declines in phytoplankton
      may have positive effects on benthic PP at the ecosystem scale. Have these lakes
      experienced oligotrophication (a reduction of algal production), or simply a
      shift in autotrophic structure with no net decline in PP? Benthic contributions
      to ecosystem PP are rarely measured in large aquatic systems, but our
      calculations based on productivity rates from the Great Lakes indicate that a
      significant proportion (up to one half, in Lake Huron) of their whole-lake
      production may be benthic. The large declines (5-45%) in phytoplankton production
      in the Great Lakes from the 1970s to 2000s may be substantially compensated by
      benthic PP, which increased by up to 190%. Thus, the autotrophic productive
      capacity of large aquatic ecosystems may be relatively resilient to shifts in
      trophic status, due to a redirection of production to the near-shore benthic
      zone, and large lakes may exhibit shifts in autotrophic structure analogous to
      the regime shifts seen in shallow lakes.

PMID- 27029573
TI  - Perceived Acceptance From Outsiders Shapes Security in Romantic Relationships:
      The Overgeneralization of Extradyadic Experiences.
AB  - Romantic relationships unfold in the context of people's other interpersonal
      relationships, and processes that occur in those other relationships have been
      shown to affect the functioning of romantic relationships. In accordance with
      this perspective, two dyadic daily report studies demonstrated that people
      generalize experiences of interpersonal acceptance and rejection from other
      people onto their romantic partners. Participants felt more confident that they
      were valued by their romantic partners on days they experienced acceptance,
      relative to rejection, from outsiders. In addition, this overgeneralization of
      daily extradyadic acceptance and rejection had prospective effects on romantic
      relationship security the following day, was independent of the romantic
      partner's actual relationship evaluations on each day, was partially mediated by
      daily self-esteem, and predicted daily enactment of prosocial and antisocial
      behaviors toward romantic partners. These results suggest that overgeneralization
      of daily acceptance and rejection from outsiders shapes the functioning of
      romantic relationships. 

PMID- 27029574
TI  - What Do You Want in a Marriage? Examining Marriage Ideals in Taiwan and the
      United States.
AB  - Four studies investigated ideal standards for one's marital partner and
      relationship held by Taiwan Chinese and European Americans. We first generated a
      list of attributes that tapped lay representations of marriage ideals based on
      free responses from Chinese and European Americans, and we uncovered attributes
      describing extended family that were overlooked in Western research (Study 1). We
      found similar ideal knowledge structures across the two cultural groups;
      importantly, Chinese prioritized ideals denoting financial resources and extended
      family to a greater extent than did European Americans (Study 2). These cultural
      differences were explained by interdependent self-construal (Study 3). Finally,
      the agreement between ideals and perceptions of current partner/relationship was
      related to positive relationship outcomes in both cultural groups (Study 4). Our
      research highlights both cultural similarities and differences in the content,
      structure, endorsement, and evaluative functions of ideals in Chinese and Western
      cultural contexts.

PMID- 27029575
TI  - Values Stability and Change in Adulthood: A 3-Year Longitudinal Study of Rank
      Order Stability and Mean-Level Differences.
AB  - Recent studies have examined whether values change across time. The present study
      investigates both rank-order stability and mean-level differences in core values-
      and whether age and sex moderate stability and change--over 3 years using a
      national probability sample (from 25 to 75 years;N= 3,962). Value priorities were
      highly stable, except for Conservation values among women, which peaked in
      stability at age 50 and decreased afterward. Older adults and women placed
      greater emphasis on values relating to the welfare of others and preservation of
      traditional practices and stability (Self-Transcendence and Conservation values).
      Younger individuals and men tended to more highly value the pursuit of status and
      power, and independent thought and behavior (Self-Enhancement and Openness to
      Change). The results are consistent with a life span perspective on values
      development and indicate values may change slowly throughout life as a reflection
      of biological and psychological maturation.

PMID- 27029576
TI  - Smiling on the Inside: The Social Benefits of Suppressing Positive Emotions in
      Outperformance Situations.
AB  - Although expressing positive emotions is typically socially rewarded, in the
      present work, we predicted that people suppress positive emotions and thereby
      experience social benefits when outperformed others are present. We tested our
      predictions in three experimental studies with high school students. In Studies 1
      and 2, we manipulated the type of social situation (outperformance vs. non
      outperformance) and assessed suppression of positive emotions. In both studies,
      individuals reported suppressing positive emotions more in outperformance
      situations than in non-outperformance situations. In Study 3, we manipulated the
      social situation (outperformance vs. non-outperformance) as well as the
      videotaped person's expression of positive emotions (suppression vs. expression).
      The findings showed that when outperforming others, individuals were indeed
      evaluated more positively when they suppressed rather than expressed their
      positive emotions, and demonstrate the importance of the specific social
      situation with respect to the effects of suppression. 

PMID- 27029577
TI  - Forgive and Forget, or Forgive and Regret? Whether Forgiveness Leads to Less or
      More Offending Depends on Offender Agreeableness.
AB  - How does forgiveness predict the likelihood of reoffending? One survey study, one
      experiment, one 4-year longitudinal study, and one 2-week diary study examined
      the implications of forgiveness for reoffending in relationships. In all four
      studies, agreeableness interacted with partner forgiveness to predict subsequent
      offending; partner forgiveness was negatively associated with subsequent
      offending among more agreeable people but positively associated with subsequent
      offending among less agreeable people. Furthermore, Study 4 demonstrated a unique
      mechanism of each simple effect; relatively agreeable people engaged in fewer
      transgressions against more forgiving partners because they felt obligated to
      refrain from transgressing against such partners whereas relatively disagreeable
      people engaged in more transgressions against more forgiving partners because
      they perceived those partners were less easily angered. These studies indicate
      that completely understanding the intrapersonal and interpersonal consequences of
      forgiveness requires recognizing the dyadic nature of forgiveness and attending
      to qualities of the offender. 

PMID- 27029578
TI  - Living in a Genetic World: How Learning About Interethnic Genetic Similarities
      and Differences Affects Peace and Conflict.
AB  - Information about the degree of one's genetic overlap with ethnic outgroups has
      been emphasized in genocides, is frequently learned about through media
      reporting, and is increasingly being accessed via personal genetic testing
      services. However, the consequence of learning about whether your own ethnic
      group is either genetically related to or genetically distinct from a disliked
      ethnic group remains unknown. Across four experiments, using diverse samples,
      measures and contexts, we demonstrate that altering perceptions of genetic
      overlap between groups in conflict--in this case Arabs and Jews--impacts factors
      that are directly related to interethnic hostility (e.g., aggressive behaviors,
      support of conflict-related policies). Our findings indicate that learning about
      the genetic difference between oneself and an ethnic outgroup may contribute to
      the promotion of violence, whereas learning about the similarities may be a vital
      step toward fostering peace in some contexts. Possible interventions and
      implications are discussed.

PMID- 27029579
TI  - Which Basic Rules Underlie Social Judgments? Agency Follows a Zero-Sum Principle
      and Communion Follows a Non-Zero-Sum Principle.
AB  - How are people who generally see others positively evaluated themselves? We
      propose that the answer to this question crucially hinges on the content domain:
      We hypothesize that Agency follows a "zero-sum principle" and therefore people
      who see others ashighin Agency are perceived aslowin Agency themselves. In
      contrast, we hypothesize that Communion follows a "non-zero-sum principle" and
      therefore people who see others ashighin Communion are perceived ashighin
      Communion themselves. We tested these hypotheses in a round-robin and a half
      block study. Perceiving others as agentic was indeed linked to being perceived as
      low in Agency. To the contrary, perceiving others as communal was linked to being
      perceived as high in Communion, but only when people directly interacted with
      each other. These results help to clarify the nature of Agency and Communion and
      offer explanations for divergent findings in the literature. 

PMID- 27029581
TI  - New abortion guidance in Northern Ireland places greater emphasis on women's
      health.

PMID- 27029580
TI  - Identification of the pXO1 plasmid in attenuated Bacillus anthracis vaccine
      strains.
AB  - Anthrax toxins and capsule are the major virulence factors of Bacillus anthracis.
      They are encoded by genes located on the plasmids pXO1 and pXO2, respectively.
      The vaccine strain Pasteur II was produced from high temperature subcultures of
      B. anthracis, which resulted in virulence attenuation through the loss of the
      plasmid pXO1. However, it is unclear whether the high temperature culture
      completely abolishes the plasmid DNA or affects the replication of the plasmid
      pXO1. In this study, we tested 3 B. anthracis vaccine strains, including Pasteur
      II from France, Qiankefusiji II from Russia, and Rentian II from Japan, which
      were all generated from subcultures at high temperatures. Surprisingly, we
      detected the presence of pXO1 plasmid DNA using overlap PCR in all these vaccine
      strains. DNA sequencing analysis of overlap PCR products further confirmed the
      presence of pXO1. Moreover, the expression of the protective antigen (PA) encoded
      on pXO1 was determined by using SDS-PAGE and western blotting. In addition, we
      mimicked Pasteur's method and exposed the A16R vaccine strain, which lacks the
      pXO2 plasmid, to high temperature, and identified the pXO1 plasmid in the
      subcultures at high temperatures. This indicated that the high temperature
      treatment at 42.5 degrees C was unable to eliminate pXO1 plasmid DNA from B.
      anthracis. Our results suggest that the attenuation of the Pasteur II vaccine
      strain is likely due to the impact of high temperature stress on plasmid
      replication, which in turn limits the copy number of pXO1. Our data provide new
      insights into the mechanisms of the remaining immunogenicity and toxicity of the
      vaccine strains.

PMID- 27029582
TI  - Working capacity of patients with Parkinson's disease - A systematic review.
AB  - INTRODUCTION: Parkinson's disease (PD) is characterized by motor and non-motor
      symptoms and has a median age-of-onset around 55 years. Many PD patients are thus
      diagnosed before reaching retirement age and it is likely that they are
      confronted with a reduced working capacity or loss of employment. This systematic
      literature review gives an overview of the research conducted on work capacity in
      PD. METHODS: A systematic literature search was performed in PsycINFO and PubMed
      (Keywords: "Parkinson" or "Parkinson's disease" combined with "employment",
      "work", "working", "retire" or "retirement"). RESULTS: Thirteen studies were
      identified and showed that PD patients retired 4-7 years earlier than the general
      population. Furthermore, 23%-75% of patients report that they retired early
      because of PD and slowness and fatigue were reported as the most debilitating
      symptoms in relation to working capacity. Early retirement of PD patients is
      associated with high societal costs and a high loss of individual lifetime
      earnings. Although many employed PD patients asked for adjustments at their
      workplace, their employers did not always support these. CONCLUSIONS: PD has a
      detrimental effect on working capacity and is associated with high costs.
      Employed PD patients do not, however, always receive the support they need. It is
      therefore very relevant that employers and patients are informed about strategies
      and techniques developed for counteracting symptoms of PD which might support
      patients to stay in the workforce for a longer period of time.

PMID- 27029583
TI  - Differential Potency of 2,6-Dimethylcyclohexanol Isomers for Positive Modulation
      of GABAA Receptor Currents.
AB  - GABAA receptors meet all of the pharmacological requirements necessary to be
      considered important targets for the action of general anesthetic agents in the
      mammalian brain. In the following patch-clamp study, the relative modulatory
      effects of 2,6-dimethylcyclohexanol diastereomers were investigated on human
      GABAA (alpha1beta3gamma2s) receptor currents stably expressed in human embryonic
      kidney cells. Cis,cis-, trans,trans-, and cis,trans-isomers were isolated from
      commercially available 2,6-dimethylcyclohexanol and were tested for positive
      modulation of submaximal GABA responses. For example, the addition of 30 MUM
      cis,cis-isomer resulted in an approximately 2- to 3-fold enhancement of the EC20
      GABA current. Coapplications of 30 MUM 2,6-dimethylcyclohexanol isomers produced
      a range of positive enhancements of control GABA responses with a rank order for
      positive modulation: cis,cis > trans,trans >= mixture of isomers > > cis,trans
      isomer. In molecular modeling studies, the three cyclohexanol isomers bound with
      the highest binding energies to a pocket within transmembrane helices M1 and M2
      of the beta3 subunit through hydrogen-bonding interactions with a glutamine at
      the 224 position and a tyrosine at the 220 position. The energies for binding to
      and hydrogen-bond lengths within this pocket corresponded with the relative
      potencies of the agents for positive modulation of GABAA receptor currents
      (cis,cis > trans,trans > cis,trans-2,6-dimethylcyclohexanol). In conclusion, the
      stereochemical configuration within the dimethylcyclohexanols is an important
      molecular feature in conferring positive modulation of GABAA receptor activity
      and for binding to the receptor, a consideration that needs to be taken into
      account when designing novel anesthetics with enhanced therapeutic indices.

PMID- 27029584
TI  - Enolate-Forming Phloretin Pharmacophores: Hepatoprotection in an Experimental
      Model of Drug-Induced Toxicity.
AB  - Drug-induced toxicity is often mediated by electrophilic metabolites, such as
      bioactivation of acetaminophen (APAP) to N-acetyl-p-benzoquinone imine (NAPQI).
      We have shown that APAP hepatotoxicity can be prevented by 2-acetylcyclopentanone
      (2-ACP). This 1,3-dicarbonyl compound ionizes to form an enolate nucleophile that
      scavenges NAPQI and other electrophilic intermediates. In this study, we expanded
      our investigation of enolate-forming compounds to include analyses of the
      phloretin pharmacophores, 2',4',6'-trihydroxyacetophenone (THA) and
      phloroglucinol (PG). Studies in a mouse model of APAP overdose showed that THA
      provided hepatoprotection when given either by intraperitoneal injection or oral
      administration, whereas PG was hepatoprotective only when given
      intraperitoneally. Corroborative research characterized the molecular
      pharmacology (efficacy, potency) of 2-ACP, THA, and PG in APAP-exposed isolated
      mouse hepatocytes. For comparative purposes, N-acetylcysteine (NAC)
      cytoprotection was also evaluated. Measurements of multiple cell parameters
      (e.g., cell viability, mitochondrial membrane depolarization) indicated that THA
      and, to a lesser extent, PG provided concentration-dependent protection against
      APAP toxicity, which exceeded that of 2-ACP or NAC. The enolate-forming compounds
      and NAC truncated ongoing APAP exposure and thereby returned intoxicated
      hepatocytes toward normal viability. The superior ability of THA to protect is
      related to multifaceted modes of action that include metal ion chelation, free
      radical trapping, and scavenging of NAPQI and other soft electrophiles involved
      in oxidative stress. The rank order of potency for the tested cytoprotectants was
      consistent with that determined in a parallel mouse model. These data suggest
      that THA or a derivative might be useful in treating drug-induced toxicities and
      other conditions that involve electrophile-mediated pathogenesis.

PMID- 27029585
TI  - TASP0434299: A Novel Pyridopyrimidin-4-One Derivative as a Radioligand for
      Vasopressin V1B Receptor.
AB  - A novel pyridopyrimidin-4-one derivative, N-tert-butyl-2-[2-(3-methoxyphenyl)-6
      [3-(morpholin-4-yl)propoxy]-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl]acetamide
      (TASP0434299), was characterized as a radioligand candidate for arginine
      vasopressin 1B (V1B) receptor. TASP0434299 exhibited high binding affinities for
      human and rat V1B receptors with IC50 values of 0.526 and 0.641 nM, respectively,
      and potent antagonistic activity at the human V1B receptor with an IC50 value of
      0.639 nM without apparent binding affinities for other molecules at 1 MUM.
      [(3)H]TASP0434299 bound to membranes expressing the human V1B receptor as well as
      those prepared from the rat anterior pituitary in a saturable manner. The binding
      of [(3)H]TASP0434299 to the membranes was dose-dependently displaced by several
      ligands for the V1B receptor. In addition, the intravenous administration of
      [(3)H]TASP0434299 to rats produced a saturable radioactive accumulation in the
      anterior pituitary where the V1B receptor is enriched, and it was dose
      dependently blocked by the oral administration of 2-[2-(3-chloro-4-fluorophenyl)
      6-[3-(morpholin-4-yl)propoxy]-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl]-N
      isopropylacetamide hydrochloride, a V1B receptor antagonist, indicating that
      [(3)H]TASP0434299 can be used as an in vivo radiotracer to measure the occupancy
      of the V1B receptor. Finally, the intravenous administration of
      [(11)C]TASP0434299 provided positron emission tomographic images of the V1B
      receptor in the pituitary in an anesthetized monkey, and the signal was blocked
      by pretreatment with an excess of unlabeled TASP0434299. These results indicate
      that radiolabeled TASP0434299 is the first radioligand to be capable of
      quantifying the V1B receptor selectively in both in vitro and in vivo studies and
      will provide a clinical biomarker for determining the occupancy of the V1B
      receptor during drug development or for monitoring the levels of the V1B receptor
      in diseased conditions.

PMID- 27029586
TI  - The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and
      Differentiation.
AB  - The microtubule-associated protein lissencephaly 1 (Lis1) is a key regulator of
      cell division during stem cell renewal and differentiation. In this study, we
      examined the role of Lis1 in T lymphocyte homeostasis and fate diversification in
      response to microbial infection. T cell-specific deletion of Lis1 resulted in
      depletion of the peripheral CD4(+) and CD8(+) T lymphocyte pool owing to a loss
      of homeostatic, cytokine-induced proliferation. In contrast, cognate Ag-triggered
      proliferation was much less affected, enabling Lis1-deficient CD8(+) T cells to
      differentiate into terminal effector cells in response to microbial infection.
      Strikingly, however, the specification of Lis1-deficient long-lived memory CD8(+)
      T lymphocytes was impaired due, in part, to an apparent failure to differentiate
      appropriately to IL-15. Taken together, these findings suggest that Lis1 plays an
      important role in T cell homeostasis and the generation of memory T lymphocytes.

PMID- 27029587
TI  - Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae
      Induced Immunosuppression.
AB  - Intact, inactivated Streptococcus pneumoniae [including the unencapsulated S.
      pneumoniae, serotype 2 strain (R36A)] markedly inhibits the humoral immune
      response to coimmunized heterologous proteins, a property not observed with
      several other intact Gram-positive or Gram-negative bacteria. In this study, we
      determined the nature of this immunosuppressive property. Because
      phosphorylcholine (PC), a major haptenic component of teichoic acid in the S.
      pneumoniae cell wall, and lipoteichoic acid in the S. pneumoniae membrane were
      previously reported to be immunosuppressive when derived from filarial parasites,
      we determined whether R36A lacking PC (R36A(pc-)) was inhibitory. Indeed,
      although R36A(pc-) exhibited a markedly reduced level of inhibition of the IgG
      response to coimmunized chicken OVA (cOVA), no inhibition was observed when using
      several other distinct PC-expressing bacteria or a soluble, protein-PC conjugate.
      Further, treatment of R36A with periodate, which selectively destroys PC
      residues, had no effect on R36A-mediated inhibition. Because R36A(pc-) also lacks
      choline-binding proteins (CBPs) that require PC for cell wall attachment, and
      because treatment of R36A with trypsin eliminated its inhibitory activity, we
      incubated R36A in choline chloride, which selectively strips CBPs from its
      surface. R36A lacking CBPs lost most of its inhibitory property, whereas the
      supernatant of choline chloride-treated R36A, containing CBPs, was markedly
      inhibitory. Coimmunization studies using cOVA and various S. pneumoniae mutants,
      each genetically deficient in one of the CBPs, demonstrated that only S.
      pneumoniae lacking the CBP pneumococcal surface protein A lost its ability to
      inhibit the IgG anti-cOVA response. These results strongly suggest that PspA
      plays a major role in mediating the immunosuppressive property of S. pneumoniae.

PMID- 27029588
TI  - Metabolic Reprogramming of Host Cells by Virulent Francisella tularensis for
      Optimal Replication and Modulation of Inflammation.
AB  - A shift in macrophage metabolism from oxidative phosphorylation to aerobic
      glycolysis is a requirement for activation to effectively combat invading
      pathogens. Francisella tularensis is a facultative intracellular bacterium that
      causes an acute, fatal disease called tularemia. Its primary mechanism of
      virulence is its ability to evade and suppress inflammatory responses while
      replicating in the cytosol of macrophages. The means by which F. tularensis
      modulates macrophage activation are not fully elucidated. In this study, we
      demonstrate that virulent F. tularensis impairs production of inflammatory
      cytokines in primary macrophages by preventing their shift to aerobic glycolysis,
      as evidenced by the downregulation of hypoxia inducible factor 1alpha and failure
      to upregulate pfkfb3 We also show that Francisella capsule is required for this
      process. In addition to modulating inflammatory responses, inhibition of
      glycolysis in host cells is also required for early replication of virulent
      Francisella Taken together, our data demonstrate that metabolic reprogramming of
      host cells by F. tularensis is a key component of both inhibition of host defense
      mechanisms and replication of the bacterium.

PMID- 27029589
TI  - Creatine kinase enzyme level correlates positively with serum creatinine and lean
      body mass, and is a prognostic factor for survival in amyotrophic lateral
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal
      neurodegenerative condition for which there is no single diagnostic test or
      biomarker. The level of the creatine kinase (CK) enzyme in serum may be mild to
      moderately elevated in some patients with ALS, the precise cause of which and its
      behaviour with disease progression is unknown. The aim of this study was to
      examine the usefulness of monitoring CK serially during the ALS disease
      trajectory and to determine whether CK levels mirror disease progression.
      METHODS: This was a prospective observational cohort study, using the clinical
      database of the olesoxime (TRO19622) investigational medicinal product trial.
      RESULTS: The baseline CK was raised in 52% of the trial participants with the
      mean CK +/- SD being 257 +/- 239 U/l. The mean CK was significantly higher in
      male participants than in female participants (P < 0.001) and amongst
      participants with limb onset ALS compared to participants with bulbar onset ALS
      (P < 0.001). There was no significant difference in the CK levels between upper
      limb and lower limb onset disease (P = 0.746). The CK level co-related positively
      with serum creatinine and estimated lean body mass but there was no relationship
      between CK and muscle scores and limb function. A higher CKlog was associated
      with significantly better survival, even when adjusted for prognostic co-variants
      (P = 0.013). CONCLUSIONS: The serum CK level seems to be an independent
      prognostic factor for survival in ALS. The cellular mechanism of CK enzyme
      suggests that it may be upregulated to provide energy in the face of metabolic
      stress in ALS.

PMID- 27029590
TI  - eHealth and quality in health care: implementation time.
AB  - The use of information and communication technologies in health and health care
      could improve healthcare quality in many ways. Today's evidence base demonstrates
      the (cost-)effectiveness of online education, self-management support and tele
      monitoring in several domains of health and care. While new results gradually
      provide more evidence for eHealth's impact on quality issues, now is the time to
      come to grips with implementation issues. Documented drawbacks such as low
      acceptance, low adoption or low adherence need our attention today to make the
      most of eHealth' potential. Improvement science is beginning to deliver the tools
      to address these persistent behavioural and cultural issues. The ceHRes Roadmap,
      for instance, is a plural and pragmatic approach that includes users' needs. It
      is now imperative to improve our implementation strategies in order to scale up
      eHealth technologies. This will accelerate the much needed transformation of our
      healthcare systems and sustain access, affordability and quality for all in the
      near future. 

PMID- 27029591
TI  - Qualitative analysis of US Department of veterans affairs mental health clinician
      perspectives on patient-centered care.
AB  - OBJECTIVE: Enhanced patient involvement in care has the potential to improve
      patient experiences and health outcomes. As such, large national and global
      healthcare systems and organizations, including the US Department of Veterans
      Affairs (VA), have made patient-centered care a primary goal. Little is known
      about mental health clinician perspectives on, and experiences with, providing
      patient-centered care. Our main objective was to better understand VA mental
      health clinicians' perceptions of patient-centered care, and ascertain possible
      facilitators and barriers to patient-centered practices in mental health
      settings. DESIGN: Qualitative study of six focus groups conducted in late 2013.
      SETTING AND PARTICIPANTS: Thirty-five mental health clinicians and staff from a
      large VA Medical Center. OUTCOMES: Transcripts were analyzed using an inductive
      and deductive thematic analysis approach. RESULTS: Participants described patient
      centered care ideally as a process of shared discovery, and expressed general
      enthusiasm for patient-centered care. Participants described several ongoing
      patient-centered care practices but conveyed concerns about the practicalities of
      its full implementation. Participants expressed a strong desire to change the
      current biomedical culture and policies of the institution that may hinder
      clinicians' flexibility and clinician-clinician collaboration when serving
      patients. In particular, clinicians worried about being held responsible for
      addressing all of the needs or goals that a patient may identify. CONCLUSIONS: If
      patient-centered care is to be practiced fully in mental health settings,
      healthcare institutions need to develop multimodal strategies to enhance
      clinician-clinician and clinician-patient collaborations to promote and support a
      focus on discovery and shared accountability for outcomes.

PMID- 27029592
TI  - Virtual obesity collaborative with and without decision-support technology.
AB  - OBJECTIVE: The purpose of this study was to evaluate school-based health center
      (SHBC) provider adherence to guidelines for identification and assessment of
      childhood obesity after participation in a virtual Health Disparities Learning
      Collaborative with and without HeartSmartKidsTM, decision-support technology with
      tailored patient education. DESIGN AND SETTING: A cluster randomized comparative
      effectiveness trial was conducted with 24 SBHCs from six states. PARTICIPANTS:
      The sample consisted of 33 SBHC providers and review of medical charts at three
      time points. Chart data were collected at baseline (n = 850), after training (n =
      691) and 6 months after training (n = 612). MAIN OUTCOME MEASURES: Charts from a
      random sample of youth 5-12 years making well-child visits were examined for the
      documentation of: BMI percentile, accurate weight diagnosis based upon BMI
      percentile, blood pressure percentile, and ordering appropriate laboratory
      assessment of obese youth >=10 years old. RESULTS: Percentage of overweight/obese
      children in this study was 40.4-47.2%. For both the HeartSmartKidsTM and non
      HeartSmartKidsTM groups, provider adherence significantly improved after training
      for BMI percentile and blood pressure percentile documentation, as well as
      correct diagnosis for overweight and obese. Implementation of the
      HeartSmartKidsTM was variable at the technology sites and differences in
      identification and assessment were not found between groups. CONCLUSION: The
      virtual collaborative approach to quality improvement resulted in improved
      adherence to guidelines for identification and assessment of overweight/obese
      children. The impact of the training with and without HeartSmartKidsTM on patient
      outcomes needs to be evaluated. Coaching on implementation of technology needs to
      be included in future work.

PMID- 27029593
TI  - The Point-of-Care Laboratory in Clinical Microbiology.
AB  - Point-of-care (POC) laboratories that deliver rapid diagnoses of infectious
      diseases were invented to balance the centralization of core laboratories. POC
      laboratories operate 24 h a day and 7 days a week to provide diagnoses within 2
      h, largely based on immunochromatography and real-time PCR tests. In our
      experience, these tests are conveniently combined into syndrome-based kits that
      facilitate sampling, including self-sampling and test operations, as POC
      laboratories can be operated by trained operators who are not necessarily
      biologists. POC laboratories are a way of easily providing clinical microbiology
      testing for populations distant from laboratories in developing and developed
      countries and on ships. Modern Internet connections enable support from core
      laboratories. The cost-effectiveness of POC laboratories has been established for
      the rapid diagnosis of tuberculosis and sexually transmitted infections in both
      developed and developing countries. 

PMID- 27029597
TI  - Propensity score analysis of outcomes following laparoscopic or open liver
      resection for hepatocellular carcinoma.
AB  - BACKGROUND: Liver resection is a potentially curative approach for hepatocellular
      carcinoma (HCC). Laparoscopic liver resections may reduce complication rates,
      especially in patients with cirrhosis. The aim of this study was to compare the
      results of laparoscopic liver resection with those of open liver resection for
      HCC. METHODS: Patients with cirrhosis who underwent minor liver resections for
      HCC from 2006 to 2013 were identified retrospectively from a prospective database
      according to the technique adopted (laparoscopic or open). Short- and long-term
      outcomes were compared between the two groups before and after 1 : 1 propensity
      score matching. RESULTS: A total of 269 patients were considered: 226 who
      underwent open liver resection and 43 who had a laparoscopic procedure. The two
      groups differed at baseline in terms of median age, sex, performance status,
      tumour location and type of resection. After propensity score matching, two
      comparable groups of 43 patients each were obtained. Intraoperative bleeding,
      margin clearance and operative mortality were similar in the two groups, whereas
      complication rates were lower (49 versus 19 per cent in open versus laparoscopic
      groups respectively; P = 0.004) and median hospital stay was shorter (8 versus 5
      days; P < 0.001) in the laparoscopic group. On multivariable logistic regression
      analysis, the only independent factor that reduced the risk of postoperative
      complications was the use of laparoscopy (odds ratio 0.12, 95 per cent c.i. 0.03
      to 0.55; P = 0.006). Median overall survival was 57.8 months in the open group
      and 48.8 months in the laparoscopic group (P = 0.802). Median disease-free
      survival was 31.7 and 25.5 months respectively (P = 0.990). CONCLUSION: In
      comparison with the open approach, laparoscopic minor liver resections for HCC
      improved short-term outcomes, with similar survival results.

PMID- 27029596
TI  - Neogenin recruitment of the WAVE regulatory complex maintains adherens junction
      stability and tension.
AB  - To maintain tissue integrity during epithelial morphogenesis, adherens junctions
      (AJs) must resist the mechanical stresses exerted by dynamic tissue movements.
      Junctional stability is dependent on actomyosin contractility within the actin
      ring. Here we describe a novel function for the axon guidance receptor, Neogenin,
      as a key component of the actin nucleation machinery governing junctional
      stability. Loss of Neogenin perturbs AJs and attenuates junctional tension.
      Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory
      complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain
      and the WRC is crucial for the spatially restricted recruitment of the WRC to the
      junction. Thus, we provide the first example of a functional WIRS-WRC interaction
      in epithelia. We further show that Neogenin regulates cadherin recycling at the
      AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it
      influences both cadherin dynamics and junctional tension. 

PMID- 27029598
TI  - Serum complement C3 levels are associated with nonalcoholic fatty liver disease
      independently of metabolic features in Chinese population.
AB  - Serum complement C3 levels are closely associated with obesity and related
      metabolic disorders. This study aimed to investigate the association between
      serum complement C3 levels with non-alcoholic fatty liver disease (NAFLD). A
      cross-sectional study was performed among adults who took their annual health
      examinations at Zhenhai Lianhua Hospital, Ningbo, China during 2014. We included
      7540 participants (5069 men and 2471 women) in this study. NAFLD patients had
      higher serum complement C3 levels (P < 0.001), and these levels were positively
      associated with both NAFLD prevalence and severity (P < 0.001). The above
      association remains true among lean and metabolic syndrome-free participants.
      Multivariable regression analysis showed that serum complement C3 was
      independently associated with risk for NAFLD (OR = 5.231; 95% CI: 3.169-8.635).
      Serum complement C3 level is positively associated with prevalence and severity
      of NAFLD, and this association is independent of obesity and metabolic syndrome. 

PMID- 27029599
TI  - Predicting oral relative bioavailability of arsenic in soil from in vitro
      bioaccessibility.
AB  - Several investigations have been conducted to develop in vitro bioaccessibility
      (IVBA) assays that reliably predict in vivo oral relative bioavailability (RBA)
      of arsenic (As). This study describes a meta-regression model relating soil As
      RBA and IVBA that is based upon data combined from previous investigations that
      examined the relationship between As IVBA and RBA when IVBA was determined using
      an extraction of soil in 0.4 M glycine at pH 1.5. Data used to develop the model
      included paired IVBA and RBA estimates for 83 soils from various types of sites
      such as mining, smelting, and pesticide or herbicide application. The following
      linear regression model accounted for 87% of the observed variance in RBA (R(2) =
      .87): RBA(%) = 0.79 * IVBA(%) + 3. This regression model is more robust than
      previously reported models because it includes a larger number of soil samples,
      and also accounts for variability in RBA and IVBA measurements made on samples
      collected from sites contaminated with different As sources and conducted in
      different labs that have utilized different experimental models for estimating
      RBA. 

PMID- 27029600
TI  - Long-term survival after resections for pancreatic ductal adenocarcinoma. Single
      centre study.
AB  - AIM: To analyse the 5-year survival rate of patients undergoing radical surgery
      for pancreatic ductal adenocarcinoma (PDAC) and to identify prognostic factors.
      METHODS: A prospectively maintained database of 90 consecutive patients who
      underwent radical resection for PDAC was analysed. Survival was evaluated using
      the Kaplan-Meier method. Log-rank test and Cox regression analysis were used for
      the evaluation of prognostic factors. P values less than 0.05 were considered
      significant. RESULTS: Mean age (+/- standard deviation) was 63.2+/-8.6 years
      (female 28.9% and male 71.1%). Tumour localisation was in the head in 76 (84.5%),
      multifocal in 3 (3.3%) and in the body/tail in 11 (12.2%). Pancreatic head
      resection was performed in 75 (83.3%), total pancreatectomy in 4 (4.4%) and
      distal pancreatectomy with splenectomy in 11 (12.2%), with standard
      lymphadenectomy. Venous resection was in 4 (4.4%). Thirty-day and in-hospital
      mortality occurred in 1 (1.1%), 90-day mortality was 3.3%. On univariate analysis
      absence of perineural and vascular invasion, stage, absence of lymph node
      infiltration and no need for transfusion were associated with improved overall
      survival. On multivariate analysis vascular invasion HR=3.137 (95%CI: 1.692
      5.816; P = 0.0003) and postoperative complications HR=2.004 (95%CI: 1.198-3.354;
      P = 0.008) were identified as significant independent predictors of survival. The
      five-year survival rate was 18.9%, with five-year recurrence-free survival of
      16.7%. CONCLUSION: Vascular invasion and postoperative complications were
      independent prognostic factors after curative resections of pancreatic cancer in
      studied cohort.

PMID- 27029601
TI  - Electrochemical lithiation/delithiation of SnP2O7 observed by in situ XRD and ex
      situ7Li/31P NMR, and 119Sn Mossbauer spectroscopy.
AB  - SnP2O7 was prepared by a sol-gel route. The structural changes of tin
      pyrophosphate during the electrochemical lithiation were followed by using in
      situ XRD measurements that reveal the existence of a crystalline phase at the
      beginning of the discharge process. Nevertheless, it becomes amorphous after the
      full discharge as a result of a conversion reaction leading to the formation of
      LixSny alloys. The electrochemical tests show a high capacity with high retention
      upon cycling. To better understand the reaction mechanism of SnP2O7 with Li,
      several techniques were applied, such as ex situ(119)Sn Mossbauer and ex
      situ(7)Li and (31)P NMR spectroscopies with which we can follow the changes in
      the local environment of each element during cycling. 

PMID- 27029602
TI  - Highly Selective Photothermal Therapy by a Phenoxylated-Dextran-Functionalized
      Smart Carbon Nanotube Platform.
AB  - Near-infrared (NIR) photothermal therapy using biocompatible single-walled carbon
      nanotubes (SWNTs) is advantageous because as-produced SWNTs, without additional
      size control, both efficiently absorb NIR light and demonstrate high photothermal
      conversion efficiency. In addition, covalent attachment of receptor molecules to
      SWNTs can be used to specifically target infected cells. However, this technique
      interrupts SWNT optical properties and inevitably lowers photothermal conversion
      efficiency and thus remains major hurdle for SWNT applications. This paper
      presents a smart-targeting photothermal therapy platform for inflammatory disease
      using newly developed phenoxylated-dextran-functionalized SWNTs. Phenoxylated
      dextran is biocompatible and efficiently suspends SWNTs by noncovalent pi-pi
      stacking, thereby minimizing SWNT bundle formations and maintaining original SWNT
      optical properties. Furthermore, it selectively targets inflammatory macrophages
      by scavenger-receptor binding without any additional receptor molecules;
      therefore, its preparation is a simple one-step process. Herein, it is
      experimentally demonstrated that phenoxylated dextran-SWNTs (pD-SWNTs) are also
      biocompatible, selectively penetrate inflammatory macrophages over normal cells,
      and exhibit high photothermal conversion efficiency. Consequently, NIR laser
      triggered macrophage treatment can be achieved with high accuracy by pD-SWNT
      without damaging receptor-free cells. These smart targeting materials can be a
      novel photothermal agent candidate for inflammatory disease.

PMID- 27029595
TI  - Zika Virus.
AB  - Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus
      and the family Flaviviridae. ZIKV was first isolated from a nonhuman primate in
      1947 and from mosquitoes in 1948 in Africa, and ZIKV infections in humans were
      sporadic for half a century before emerging in the Pacific and the Americas. ZIKV
      is usually transmitted by the bite of infected mosquitoes. The clinical
      presentation of Zika fever is nonspecific and can be misdiagnosed as other
      infectious diseases, especially those due to arboviruses such as dengue and
      chikungunya. ZIKV infection was associated with only mild illness prior to the
      large French Polynesian outbreak in 2013 and 2014, when severe neurological
      complications were reported, and the emergence in Brazil of a dramatic increase
      in severe congenital malformations (microcephaly) suspected to be associated with
      ZIKV. Laboratory diagnosis of Zika fever relies on virus isolation or detection
      of ZIKV-specific RNA. Serological diagnosis is complicated by cross-reactivity
      among members of the Flavivirus genus. The adaptation of ZIKV to an urban cycle
      involving humans and domestic mosquito vectors in tropical areas where dengue is
      endemic suggests that the incidence of ZIKV infections may be underestimated.
      There is a high potential for ZIKV emergence in urban centers in the tropics that
      are infested with competent mosquito vectors such as Aedes aegypti and Aedes
      albopictus.

PMID- 27029603
TI  - Effects of single and dual species herbivory on the behavioral responses of three
      thrips species to cotton seedlings.
AB  - This study investigated the olfactory responses of 3 thrips species
      [Frankliniella schultzei Trybom, F. occidentalis Pergrande and Thrips tabaci
      Lindeman (Thysanoptera: Thripidae)] to cotton seedlings [Gossypium hirsutum L.
      (Malvales: Malvaceae)] simultaneously damaged by different combinations of
      herbivores. Cotton seedlings were damaged by foliar feeding Tetranychus urticae
      Koch (Trombidiforms: Tetranychidae), Helicoverpa armigera Hubner (Lepidoptera:
      Noctuidae), Aphis gossypii Glover (Hemiptera: Aphididae) or root feeding Tenebrio
      molitor L. (Coleoptera: Tenebrionidae). Thrips responses to plants simultaneously
      damaged by 2 species of herbivore were additive and equivalent to the sum of the
      responses of thrips to plants damaged by single herbivore species feeding alone.
      For example, F. occidentalis was attracted to T. urticae damaged plants but more
      attracted to undamaged plants than to plants damaged by H. armigera. Plants
      simultaneously damaged by low densities of T. urticae and H. armigera repelled F.
      occidentalis but as T. urticae density increased relative to H. armigera density,
      F. occidentalis attraction to coinfested plants increased proportionally. Thrips
      tabaci did not discriminate between undamaged plants and plants damaged by H.
      armigera but were attracted to plants damaged by T. urticae alone or
      simultaneously damaged by T. urticae and H. armigera. Olfactometer assays showed
      that simultaneous feeding by 2 herbivores on a plant can affect predator-prey
      interactions. Attraction of F. occidentalis to plants damaged by its T. urticae
      prey was reduced when the plant was simultaneously damaged by H. armigera, T.
      molitor, or A. gossypii and F. schultzei was more attracted to plants
      simultaneously damaged by T. urticae and H. armigera than to plants damaged by T.
      urticae alone. We conclude that plant responses to feeding by 1 species of
      herbivore are affected by responses to feeding by other herbivores. These plant
      mediated interactions between herbivore complexes affect the behavioral responses
      of thrips which vary between species and are highly context dependent.

PMID- 27029594
TI  - Pertussis: Microbiology, Disease, Treatment, and Prevention.
AB  - Pertussis is a severe respiratory infection caused by Bordetella pertussis, and
      in 2008, pertussis was associated with an estimated 16 million cases and 195,000
      deaths globally. Sizeable outbreaks of pertussis have been reported over the past
      5 years, and disease reemergence has been the focus of international attention to
      develop a deeper understanding of pathogen virulence and genetic evolution of B.
      pertussis strains. During the past 20 years, the scientific community has
      recognized pertussis among adults as well as infants and children. Increased
      recognition that older children and adolescents are at risk for disease and may
      transmit B. pertussis to younger siblings has underscored the need to better
      understand the role of innate, humoral, and cell-mediated immunity, including the
      role of waning immunity. Although recognition of adult pertussis has increased in
      tandem with a better understanding of B. pertussis pathogenesis, pertussis in
      neonates and adults can manifest with atypical clinical presentations. Such
      disease patterns make pertussis recognition difficult and lead to delays in
      treatment. Ongoing research using newer tools for molecular analysis holds
      promise for improved understanding of pertussis epidemiology, bacterial
      pathogenesis, bioinformatics, and immunology. Together, these advances provide a
      foundation for the development of new-generation diagnostics, therapeutics, and
      vaccines. 

PMID- 27029604
TI  - Gastrointestinal: Ischemic gastrointestinal manifestations in a young adult:
      Implicating a rare initial presentation of antiphospholipid syndrome.

PMID- 27029605
TI  - Contact line of adsorbed colloid-polymer droplets in theory and experiment.
AB  - The contact line between the colloid-rich bulk liquid and an adsorbed thin film
      in colloid-polymer mixtures (CPM) is studied by means of an interface
      displacement model. The interface displacement profiles are compared to laser
      scanning confocal microscopy (LSCM) images. The mixtures consist of
      poly(methylmetacrylate) (PMMA) colloids and polystyrene (PS) polymers with
      polymer-to-colloid size ratio q = 1.18. Based on the experimental parameters, the
      theoretical model predicts a contact angle for colloid-rich liquid droplets
      adsorbed on glass of thetainfinity = 59 degrees , assuming a contact line with
      infinite radius, R = infinity. When a contact-line curvature correction and a
      correction for the protein-limit character of the CPM are taken into account, a
      modest shift is obtained. The refined theory predicts theta~ 56 degrees . The
      contact angle determined visually from the LSCM images is theta~ 30 degrees . The
      model predicts a three-phase contact-line tension of tau = -1.2 * 10(-12) N
      (uncorrected) and tau = -2.3 * 10(-13) N (with protein-limit correction), which
      is physically sound both in sign and magnitude. The line tension influences the
      contact angle to a small extent due to the contact line curvature. The predicted
      width of the transition zone between the thin film and the droplet is about 2
      MUm. The effect of gravity is noticeable as a deformation near the middle of the
      droplet.

PMID- 27029607
TI  - Diffusion in a Crowded, Rearranging Environment.
AB  - It has been found in many experiments that the mean square displacement of a
      Brownian particle x(T) diffusing in a rearranging environment is strictly
      Fickian, obeying ?(x(T))(2)? ? T, but the probability distribution function for
      the displacement is not Gaussian. An explanation of this is that the diffusivity
      of the particle itself is changing as a function of time. Models for this
      diffusing diffusivity have been solved analytically in the limit of small time,
      but simulations were necessary for intermediate and large times. We show that one
      of the diffusing diffusivity models is equivalent to Brownian motion in the
      presence of a sink and introduce a class of models for which it is possible to
      find analytical solutions. Our solution gives ?(x(T))(2)? ? T for all times and
      at short times the probability distribution function of the displacement is
      exponential which crosses over to a Gaussian in the limit of long times and large
      displacements.

PMID- 27029606
TI  - Icariin attenuates titanium-particle inhibition of bone formation by activating
      the Wnt/beta-catenin signaling pathway in vivo and in vitro.
AB  - Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical
      condition following total joint arthroplasty, which can cause implant instability
      and failure. The host response to wear debris promotes bone resorption and
      impairs bone formation. We previously demonstrated that icariin suppressed wear
      debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in
      vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic
      site remains unclear. Here, we demonstrated that icariin significantly attenuated
      titanium-particle inhibition of osteogenic differentiation of mesenchymal stem
      cells (MSCs). Additionally, icariin increased bone mass and decreased bone loss
      in titanium-particle-induced osteolytic sites. Mechanistically, icariin inhibited
      decreased beta-catenin stability induced by titanium particles in vivo and in
      vitro. To confirm icariin mediated its bone-protective effects via the Wnt/beta
      catenin signaling pathway, we demonstrated that ICG-001, a selective Wnt/beta
      catenin inhibitor, attenuated the effects of icariin on MSC mineralization in
      vitro and bone formation in vivo. Therefore, icariin could induce osteogenic
      differentiation of MSCs and promote new bone formation at a titanium-particle
      induced osteolytic site via activation of the Wnt/beta-catenin signaling pathway.
      These results further support the protective effects of icariin on particle
      induced bone loss and provide novel mechanistic insights into the recognized bone
      anabolic effects of icariin and an evidence-based rationale for its use in PIO
      treatment. 

PMID- 27029608
TI  - In vivo gene therapy potentials of CRISPR-Cas9.

PMID- 27029609
TI  - Show Horse Welfare: Horse Show Competitors' Understanding, Awareness, and
      Perceptions of Equine Welfare.
AB  - The purpose of this study was to gain a better understanding of stock-type horse
      show competitors' understanding of welfare and level of concern for stock-type
      show horses' welfare. Data were collected through an online questionnaire that
      included questions relating to (a) interest and general understanding of horse
      welfare, (b) welfare concerns of the horse show industry and specifically the
      stock-type horse show industry, (c) decision-making influences, and (d) level of
      empathic characteristics. The majority of respondents indicated they agree or
      strongly agree that physical metrics should be a factor when assessing horse
      welfare, while fewer agreed that behavioral and mental metrics should be a
      factor. Respondent empathy levels were moderate to high and were positively
      correlated with the belief that mental and behavioral metrics should be a factor
      in assessing horse welfare. Respondents indicated the inhumane practices that
      most often occur at stock-type shows include excessive jerking on reins,
      excessive spurring, and induced excessive unnatural movement. Additionally,
      respondents indicated association rules, hired trainers, and hired riding
      instructors are the most influential regarding the decisions they make related to
      their horses' care and treatment. 

PMID- 27029610
TI  - ATRX binds to atypical chromatin domains at the 3' exons of zinc finger genes to
      preserve H3K9me3 enrichment.
AB  - ATRX is a SWI/SNF chromatin remodeler proposed to govern genomic stability
      through the regulation of repetitive sequences, such as rDNA, retrotransposons,
      and pericentromeric and telomeric repeats. However, few direct ATRX target genes
      have been identified and high-throughput genomic approaches are currently lacking
      for ATRX. Here we present a comprehensive ChIP-sequencing study of ATRX in
      multiple human cell lines, in which we identify the 3' exons of zinc finger genes
      (ZNFs) as a new class of ATRX targets. These 3' exonic regions encode the zinc
      finger motifs, which can range from 1-40 copies per ZNF gene and share large
      stretches of sequence similarity. These regions often contain an atypical
      chromatin signature: they are transcriptionally active, contain high levels of
      H3K36me3, and are paradoxically enriched in H3K9me3. We find that these ZNF 3'
      exons are co-occupied by SETDB1, TRIM28, and ZNF274, which form a complex with
      ATRX. CRISPR/Cas9-mediated loss-of-function studies demonstrate (i) a reduction
      of H3K9me3 at the ZNF 3' exons in the absence of ATRX and ZNF274 and, (ii)
      H3K9me3 levels at atypical chromatin regions are particularly sensitive to ATRX
      loss compared to other H3K9me3-occupied regions. As a consequence of ATRX or
      ZNF274 depletion, cells with reduced levels of H3K9me3 show increased levels of
      DNA damage, suggesting that ATRX binds to the 3' exons of ZNFs to maintain their
      genomic stability through preservation of H3K9me3.

PMID- 27029611
TI  - Enzymatic properties, evidence for in vivo expression, and intracellular
      localization of shewasin D, the pepsin homolog from Shewanella denitrificans.
AB  - The widespread presence of pepsin-like enzymes in eukaryotes together with their
      relevance in the control of multiple biological processes is reflected in the
      large number of studies published so far for this family of enzymes. By contrast,
      pepsin homologs from bacteria have only recently started to be characterized. The
      work with recombinant shewasin A from Shewanella amazonensis provided the first
      documentation of this activity in prokaryotes. Here we extend our studies to
      shewasin D, the pepsin homolog from Shewanella denitrificans, to gain further
      insight into this group of bacterial peptidases that likely represent ancestral
      versions of modern eukaryotic pepsin-like enzymes. We demonstrate that the
      enzymatic properties of recombinant shewasin D are strongly reminiscent of
      eukaryotic pepsin homologues. We determined the specificity preferences of both
      shewasin D and shewasin A using proteome-derived peptide libraries and observed
      remarkable similarities between both shewasins and eukaryotic pepsins, in
      particular with BACE-1, thereby confirming their phylogenetic proximity.
      Moreover, we provide first evidence of expression of active shewasin D in S.
      denitrificans cells, confirming its activity at acidic pH and inhibition by
      pepstatin. Finally, our results revealed an unprecedented localization for a
      family A1 member by demonstrating that native shewasin D accumulates
      preferentially in the cytoplasm. 

PMID- 27029613
TI  - Systematically probing the bottom-up synthesis of AuPAMAM conjugates for enhanced
      transfection efficiency.
AB  - BACKGROUND: Gold nanoparticles (AuNPs) have shown great promise as scaffolds for
      gene therapy vectors due to their attractive physiochemical properties which
      include biocompatibility, ease of functionalization via the nearly covalent gold
      sulfur dative bond, and surface plasmon optical properties. Previously, we
      synthesized stable AuNP-polyamidoamine (AuPAMAM) conjugates and showed their
      success in vitro as non-viral gene delivery vectors. RESULTS: In this study, we
      systematically perturbed each component of the AuPAMAM conjugates and analyzed
      the resulting effect on transfection efficiency. Due to the modular, bottom-up
      nature of the AuPAMAM synthesis, we were able to probe each step of the
      fabrication process. The relationship between each conjugation parameter and the
      function of the final vector were investigated. More than fourfold enhanced
      transfection efficiency was achieved by modifying the PAMAM concentration, PAMAM
      core chemistry, PAMAM terminus chemistry, and self-assembled monolayer
      composition of the AuPAMAM conjugates. CONCLUSIONS: This work suggest that
      AuPAMAM synthesis platform is a promising non-viral gene therapy approach and
      highlights the importance of inspecting the role of each individual constituent
      in all nanotechnology hybrid materials.

PMID- 27029614
TI  - Inflammatory response to the administration of mesenchymal stem cells in an
      equine experimental model: effect of autologous, and single and repeat doses of
      pooled allogeneic cells in healthy joints.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) transplantation has become a promising
      therapeutic choice for musculoskeletal injuries. Joint-related disorders are
      highly prevalent in horses. Therefore, these animals are considered as suitable
      models for testing MSC-based therapies for these diseases. The aim of this study
      was to investigate the clinical and inflammatory responses to intra-articular
      single and repeat dose administration of autologous or of pooled allogeneic MSCs
      in healthy equine healthy joints. Six horses were intra-articularly injected with
      a single autologous dose of bone marrow derived MSCs (BM-MSCs) and two separate
      doses of allogeneic BM-MSCs pooled from several donors. All contralateral joints
      were injected with Lactated Ringer's Solution (LRS) as the control vehicle. Signs
      of synovitis and lameness were evaluated at days 0, 1, 2, 3, 5 and 10 after
      injection. Total protein (TP), white blood cell count (WBC) and neutrophil count
      (NC) in synovial fluid were also measured at the same time-points. RESULTS: A
      mild synovial effusion without associated lameness was observed after all BM-MSCs
      injections. The second allogeneic injection caused the lowest signs of synovitis.
      Local temperature slightly increased after all BM-MSCs treatments compared to the
      controls. TP, WBC and NC in synovial fluids also increased during days 1 to 5
      after all BM-MSCs injections. Both, clinical and synovial parameters were
      progressively normalized and by day 10 post-inoculation appeared
      indistinguishable from controls. CONCLUSIONS: Intra-articular administration of
      an allogeneic pool of BM-MSCs represents a safe therapeutic strategy to enhance
      MSCs availability. Importantly, the absence of hypersensitivity response to the
      second allogeneic BM-MSCs injection validates the use of repeat dose treatments
      to potentiate the therapeutic benefit of these cells. These results notably
      contribute to the development of stem cell based therapies for equine and human
      joint diseases.

PMID- 27029615
TI  - Ambivalence and motivational interviewing with adolescents: ensuring that the
      baby does not get thrown out with the bathwater.

PMID- 27029616
TI  - Highly Sensitive, Stretchable, and Wash-Durable Strain Sensor Based on Ultrathin
      Conductive Layer@Polyurethane Yarn for Tiny Motion Monitoring.
AB  - Strain sensors play an important role in the next generation of artificially
      intelligent products. However, it is difficult to achieve a good balance between
      the desirable performance and the easy-to-produce requirement of strain sensors.
      In this work, we proposed a simple, cost-efficient, and large-area compliant
      strategy for fabricating highly sensitive strain sensor by coating a polyurethane
      (PU) yarn with an ultrathin, elastic, and robust conductive polymer composite
      (CPC) layer consisting of carbon black and natural rubber. This CPC@PU yarn
      strain sensor exhibited high sensitivity with a gauge factor of 39 and detection
      limit of 0.1% strain. The elasticity and robustness of the CPC layer endowed the
      sensor with good reproducibility over 10,000 cycles and excellent wash- and
      corrosion-resistance. We confirmed the applicability of our strain sensor in
      monitoring tiny human motions. The results indicated that tiny normal
      physiological activities (including pronunciation, pulse, expression, swallowing,
      coughing, etc.) could be monitored using this CPC@PU sensor in real time. In
      particular, the pronunciation could be well parsed from the recorded delicate
      speech patterns, and the emotions of laughing and crying could be detected and
      distinguished using this sensor. Moreover, this CPC@PU strain-sensitive yarn
      could be woven into textiles to produce functional electronic fabrics. The high
      sensitivity and washing durability of this CPC@PU yarn strain sensor, together
      with its low-cost, simplicity, and environmental friendliness in fabrication,
      open up new opportunities for cost-efficient fabrication of high performance
      strain sensing devices.

PMID- 27029618
TI  - Fruit and vegetable intake of US adults estimated by two methods: What We Eat In
      America, National Health and Nutrition Examination Survey 2009-2012.
AB  - OBJECTIVE: Estimates of fruit and vegetable (FV) consumption vary depending on
      intake definition, which may be determined by research purpose. Researchers have
      used two methods to evaluate intake: epidemiological and behavioural. The present
      study describes FV intake by adults using epidemiological v. behavioural
      approaches. DESIGN: One-day dietary intake data from What We Eat In America,
      National Health and Nutrition Examination Survey 2009-2012 were used. Sample
      weights were used to produce nationally representative estimates. FV intake (in
      cup-equivalents (CE)) was estimated using the Food Patterns Equivalents Database.
      The epidemiological method considered all FV after disaggregating foods and
      beverages. The behavioural method included foods that provided at least 0.2 CE FV
      per 100 g, and excluded sources high in fat, added sugar and Na. SETTING:
      Nationally representative survey of the US population. SUBJECTS: Adults (n 10
      563) aged >=20 years. RESULTS: For epidemiological v. behavioural, fruit intake
      was 1.1 v. 1.0 CE for males and 1.0 v. 0.9 CE for females. Vegetable intake was
      1.8 v. 1.1 CE for males and 1.5 v. 1.0 CE for females. CONCLUSIONS: The
      definition of FV intake affects estimates of consumption by the population and is
      an important consideration when planning and comparing research studies. The
      method used should align with research goals to assure accurate interpretation
      and validity of results.

PMID- 27029617
TI  - Defining the cutoff value of MGMT gene promoter methylation and its predictive
      capacity in glioblastoma.
AB  - Despite advances in the treatment of glioblastoma (GBM), median survival is 12-15
      months. O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation
      status is acknowledged as a predictive marker for temozolomide (TMZ) treatment.
      When MGMT promoter values fall into a "methylated" range, a better response to
      chemotherapy is expected. However, a cutoff that discriminates between
      "methylated" and "unmethylated" status has yet to be defined. We aimed to
      identify the best cutoff value and to find out whether variability in methylation
      profiles influences the predictive capacity of MGMT promoter methylation. Data
      from 105 GBM patients treated between 2008 and 2013 were analyzed. MGMT promoter
      methylation status was determined by analyzing 10 CpG islands by pyrosequencing.
      Patients were treated with radiotherapy followed by TMZ. MGMT promoter
      methylation status was classified into unmethylated 0-9 %, methylated 10-29 % and
      methylated 30-100 %. Statistical analysis showed that an assumed methylation
      cutoff of 9 % led to an overestimation of responders. All patients in the 10-29 %
      methylation group relapsed before the 18-month evaluation. Patients with a
      methylation status >=30 % showed a median overall survival of 25.2 months
      compared to 15.2 months in all other patients, confirming this value as the best
      methylation cutoff. Despite wide variability among individual profiles, single
      CpG island analysis did not reveal any correlation between single CpG island
      methylation values and relapse or death. Specific CpG island methylation status
      did not influence the predictive value of MGMT. The predictive role of MGMT
      promoter methylation was maintained only with a cutoff value >=30 %.

PMID- 27029619
TI  - The mechanisms for N-heterocyclic olefin-catalyzed formation of cyclic carbonate
      from CO2 and propargylic alcohols.
AB  - The mechanistic details of N-heterocyclic olefin-catalyzed formation of cyclic
      carbonate from CO2 and propargylic alcohols were investigated by DFT
      calculations. Six mechanisms, four for the formation of five-membered cyclic
      carbonate (M-A, M-B, M-B' and M-C), and two for six-membered cyclic carbonate (M
      D and M-E), were fully investigated. The energy profiles in dichloromethane
      showed that M-B is the predominant reaction with the lowest barrier of 31.99 kcal
      mol(-1), while M-C and M-D may be kinetically competitive to M-B. The very high
      activation energy of 45.37 kcal mol(-1), 57.07 kcal mol(-1) and 59.61 kcal mol(
      1) for M-A, M-B' and M-E, respectively, suggest that they are of lesser
      importance in the overall mechanism.

PMID- 27029620
TI  - A theoretical study on the hydrogen-bonding interactions between flavonoids and
      ethanol/water.
AB  - Ethanol and water are the solvents most commonly used to extract flavonoids from
      propolis. Do hydrogen-bonding interactions exist between flavonoids and
      ethanol/water? In this work, this question was addressed by using density
      functional theory (DFT) to provide information on the hydrogen-bonding
      interactions between flavonoids and ethanol/water. Chrysin and Galangin were
      chosen as the representative flavonoids. The investigated complexes included
      chrysin-H2O, chrysin-CH3CH2OH, galangin-H2O and galangin-CH3CH2OH dyads.
      Molecular geometries, hydrogen-bond binding energies, charges of monomers and
      dyads, and topological analysis were studied at the B3LYP/M062X level of theory
      with the 6-31++G(d,p) basis set. The main conclusions were: (1) nine and ten
      optimized hydrogen-bond geometries were obtained for chrysin-H2O/CH3CH2OH and
      galangin-H2O/CH3CH2OH complexes, respectively. (2) The hydrogen atoms except
      aromatic H1 and H5 and all of the oxygen atoms can form hydrogen-bonds with H2O
      and CH3CH2OH. Ethanol and water form strong hydrogen-bonds with the hydroxyl,
      carbonyl and ether groups in chrysin/galangin and form weak hydrogen-bonds with
      aromatic hydrogen atoms. Except in structures labeled A and B, chrysin and
      galangin interact more strongly with H2O than CH3CH2OH. (3) When chrysin and
      galangin form hydrogen-bonds with H2O and CH3CH2OH, charge transfers from the
      hydrogen-bond acceptor (H2O and CH3CH2OH in structures A, B, G, H, I, J) to the
      hydrogen-bond donor (chrysin and galangin in structure A, B, G, H, I, J). The
      stronger hydrogen-bond makes the hydrogen-bond donor lose more charge (A> B> G>
      H> I> J). (4) Most of the hydrogen-bonds in chrysin/galangin-H2O/CH3CH2OH
      complexes may be considered as electrostatic dominant, while C-O2...H in
      structures labeled E and C-O5...H in structures labeled J are hydrogen-bonds
      combined of electrostatic and covalent characters. H9, H7, and O4 are the
      preferred hydrogen-bonding sites. 

PMID- 27029621
TI  - A dynamics prediction of nitromethane -> methyl nitrite isomerization in external
      electric field.
AB  - As a follow-up to our investigation into the effect of external electric field on
      the chemical bond strength, the effects of external electric field on the CH3NO2 
      > CH3ONO isomerization dynamics were investigated using the MP2/6-311++G(2d,p)
      and CCSD/6-311++G(2d,p) methods. The rate constants in the absence and presence
      of various field strengths were calculated. The results show that, when the field
      strength is larger than +0.0060 a.u. along the C-NO2 bond axis, the barriers of
      the isomerization are lower than the C-NO2 bond dissociation energies, leading to
      the preferences of the isomerization over the C-NO2 bond dissociation. In this
      case, the sensitivities are higher than that in no field. However, in the other
      fields, the C-NO2 bond scission is favored and the sensitivities are almost equal
      to that in no field. Several good linear correlations are found between the field
      strengths and the changes of the bond lengths or corresponding electron
      densities. 

PMID- 27029622
TI  - A theoretical prediction of the relationships between the impact sensitivity and
      electrostatic potential in strained cyclic explosive and application to H-bonded
      complex of nitrocyclohydrocarbon.
AB  - Seven models that related the features of molecular surface electrostatic
      potentials (ESPs) above the bond midpoints and rings, statistical parameters of
      ESPs to the experimental impact sensitivities h 50 of eight strained cyclic
      explosives with the C-NO2 bonds were theoretically predicted at the DFT-B3LYP/6
      311++G** level. One of the models was used to investigate the changes of h 50 for
      the nitrocyclohydrocarbon frameworks in the H-bonded complexes of HF with
      nitrocyclopropane, nitrocyclobutane, nitrocyclopentane, and nitrocyclohexane. The
      results show that the correlation coefficients of the obtained models are small.
      When adding the effect of ring strain, the value of correlation coefficient is
      increased. According to the calculated h 50, the sensitivities in the frameworks
      are increased after hydrogen bonding. As a global feature of molecules, surface
      electrostatic potential is more available to judge the sensitivity change than
      the trigger bond dissociation energy or ring strain energy in H-bonded complex.

PMID- 27029624
TI  - Pharmaceutical Raw Material Identification Using Miniature Near-Infrared
      (MicroNIR) Spectroscopy and Supervised Pattern Recognition Using Support Vector
      Machine.
AB  - Near-infrared spectroscopy as a rapid and non-destructive analytical technique
      offers great advantages for pharmaceutical raw material identification (RMID) to
      fulfill the quality and safety requirements in pharmaceutical industry. In this
      study, we demonstrated the use of portable miniature near-infrared (MicroNIR)
      spectrometers for NIR-based pharmaceutical RMID and solved two challenges in this
      area, model transferability and large-scale classification, with the aid of
      support vector machine (SVM) modeling. We used a set of 19 pharmaceutical
      compounds including various active pharmaceutical ingredients (APIs) and
      excipients and six MicroNIR spectrometers to test model transferability. For the
      test of large-scale classification, we used another set of 253 pharmaceutical
      compounds comprised of both chemically and physically different APIs and
      excipients. We compared SVM with conventional chemometric modeling techniques,
      including soft independent modeling of class analogy, partial least squares
      discriminant analysis, linear discriminant analysis, and quadratic discriminant
      analysis. Support vector machine modeling using a linear kernel, especially when
      combined with a hierarchical scheme, exhibited excellent performance in both
      model transferability and large-scale classification. Hence, ultra-compact,
      portable and robust MicroNIR spectrometers coupled with SVM modeling can make on
      site and in situ pharmaceutical RMID for large-volume applications highly
      achievable.

PMID- 27029623
TI  - Development of a skin rash within the first week and the therapeutic effect in
      afatinib monotherapy for EGFR-mutant non-small cell lung cancer (NSCLC): Okayama
      Lung Cancer Study Group experience.
AB  - BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR
      TKIs) are now key agents in treating EGFR-mutant non-small cell lung cancer
      (NSCLC). The efficacy of gefitinib or erlotinib monotherapy can be predicted by
      the development of a skin rash. However, it has not been fully evaluated if this
      is the case with afatinib monotherapy. METHODS: We retrospectively studied 49
      consecutive patients with EGFR-mutant NSCLC who received afatinib therapy between
      2009 and 2015. The relationship of several toxicities with tumor response was
      examined. RESULTS: Grade 2, or more severe, common adverse events (AEs) included
      skin rash in 17 patients (35 %), diarrhea in 19 (39 %) and mucositis in 15 (31
      %). Of these, the number of patients who developed >=Grade 2 AEs during the first
      week after the initiation of afatinib therapy was: five patients had skin rash
      (10 %), 12 patients had diarrhea (25 %) and four patients had mucositis (8 %). As
      for an objective response, 21 (43 %) of the 49 had a partial response.
      Associating the AEs with the antitumor effect, those who had a >=Grade 2 skin
      rash within the first week tended to have a greater tumor response compared with
      those without a rash (80 vs. 39 %; p = 0.077). CONCLUSION: Our small study
      demonstrated that the early development of a skin rash might be associated with
      the response to afatinib monotherapy.

PMID- 27029625
TI  - Diffuse hypomyelination is not obligate for POLR3-related disorders.
AB  - OBJECTIVE: To report atypical MRI patterns associated with POLR3A and POLR3B
      mutations. METHODS: This was a multicenter retrospective study to collect
      neuroradiologic, clinical, and molecular data of patients with mutations in
      POLR3A and POLR3B without the classic MRI phenotype, i.e., diffuse
      hypomyelination associated with relative T2 hypointensity of the ventrolateral
      thalamus, globus pallidus, optic radiation, corticospinal tract at the level of
      the internal capsule, and dentate nucleus, cerebellar atrophy, and thinning of
      the corpus callosum. RESULTS: Eight patients were identified: 6 carried mutations
      in POLR3A and 2 in POLR3B. We identified 2 novel MRI patterns: 4 participants
      presented a selective involvement of the corticospinal tracts, specifically at
      the level of the posterior limbs of the internal capsules; 4 patients presented
      moderate to severe cerebellar atrophy. Incomplete hypomyelination was observed in
      5 participants. CONCLUSION: Diffuse hypomyelination is not an obligatory feature
      of POLR3-related disorders. Two distinct patterns, selective involvement of the
      corticospinal tracts and cerebellar atrophy, are added to the MRI presentation of
      POLR3-related disorders.

PMID- 27029626
TI  - Drawing on the right brain for aphasia recovery.

PMID- 27029627
TI  - Right hemisphere structures predict poststroke speech fluency.
AB  - OBJECTIVE: We sought to determine via a cross-sectional study the contribution of
      (1) the right hemisphere's speech-relevant white matter regions and (2)
      interhemispheric connectivity to speech fluency in the chronic phase of left
      hemisphere stroke with aphasia. METHODS: Fractional anisotropy (FA) of white
      matter regions underlying the right middle temporal gyrus (MTG), precentral gyrus
      (PreCG), pars opercularis (IFGop) and triangularis (IFGtri) of the inferior
      frontal gyrus, and the corpus callosum (CC) was correlated with speech fluency
      measures. A region within the superior parietal lobule (SPL) was examined as a
      control. FA values of regions that significantly predicted speech measures were
      compared with FA values from healthy age- and sex-matched controls. RESULTS: FA
      values for the right MTG, PreCG, and IFGop significantly predicted speech
      fluency, but FA values of the IFGtri and SPL did not. A multiple regression
      showed that combining FA of the significant right hemisphere regions with the
      lesion load of the left arcuate fasciculus-a previously identified biomarker of
      poststroke speech fluency-provided the best model for predicting speech fluency.
      FA of CC fibers connecting left and right supplementary motor areas (SMA) was
      also correlated with speech fluency. FA of the right IFGop and PreCG was
      significantly higher in patients than controls, while FA of a whole CC region of
      interest (ROI) and the CC-SMA ROI was significantly lower in patients.
      CONCLUSIONS: Right hemisphere white matter integrity is related to speech fluency
      measures in patients with chronic aphasia. This may indicate premorbid anatomical
      variability beneficial for recovery or be the result of poststroke remodeling.

PMID- 27029628
TI  - Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC
      CHAMPS Trial.
AB  - OBJECTIVE: To determine whether the addition of repetitive transcranial magnetic
      stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive
      therapy increases motor function in children with perinatal stroke and
      hemiparesis. METHODS: A factorial-design, blinded, randomized controlled trial
      (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic
      children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2
      week, goal-directed, peer-supported motor learning camp randomized to daily rTMS,
      CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and
      the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6
      months postintervention. Outcome assessors were blinded to treatment. Interim
      safety analyses occurred after 12 and 24 participants. Intention-to-treat
      analysis examined treatment effects over time (linear mixed effects model).
      RESULTS: All 45 participants completed the trial. Addition of rTMS, CIMT, or both
      doubled the chances of clinically significant improvement. Assisting Hand
      Assessment gains at 6 months were additive and largest with rTMS + CIMT (beta
      coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large
      improvements in Canadian Occupational Performance Measure scores, maximal at 6
      months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions
      were well tolerated and safe with no decrease in function of either hand.
      CONCLUSIONS: Hemiparetic children participating in intensive, psychosocial
      rehabilitation programs can achieve sustained functional gains. Addition of CIMT
      and rTMS increases the chances of improvement. CLASSIFICATION OF EVIDENCE: This
      study provides Class II evidence that combined rTMS and CIMT enhance therapy
      induced functional motor gains in children with stroke-induced hemiparetic
      cerebral palsy.

PMID- 27029629
TI  - A targeted resequencing gene panel for focal epilepsy.
AB  - OBJECTIVES: We report development of a targeted resequencing gene panel for focal
      epilepsy, the most prevalent phenotypic group of the epilepsies. METHODS: The
      targeted resequencing gene panel was designed using molecular inversion probe
      (MIP) capture technology and sequenced using massively parallel Illumina
      sequencing. RESULTS: We demonstrated proof of principle that mutations can be
      detected in 4 previously genotyped focal epilepsy cases. We searched for both
      germline and somatic mutations in 251 patients with unsolved sporadic or familial
      focal epilepsy and identified 11 novel or very rare missense variants in 5
      different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were
      predicted to be pathogenic or likely pathogenic, explaining ~0.8% of the cohort,
      and 8 were of uncertain significance based on available data. CONCLUSIONS: We
      have developed and validated a targeted resequencing panel for focal epilepsies,
      the most important clinical class of epilepsies, accounting for about 60% of all
      cases. Our application of MIP technology is an innovative approach that will be
      advantageous in the clinical setting because it is highly sensitive, efficient,
      and cost-effective for screening large patient cohorts. Our findings indicate
      that mutations in known genes likely explain only a small proportion of focal
      epilepsy cases. This is not surprising given the established clinical and genetic
      heterogeneity of these disorders and underscores the importance of further gene
      discovery studies in this complex syndrome.

PMID- 27029631
TI  - Combining rTMS and CIMT: A "one-size-fits-all" therapy for congenital
      hemiparesis?

PMID- 27029630
TI  - Delineation of the movement disorders associated with FOXG1 mutations.
AB  - OBJECTIVE: The primary objective of this research was to characterize the
      movement disorders associated with FOXG1 mutations. METHODS: We identified
      patients with FOXG1 mutations who were referred to either a tertiary movement
      disorder clinic or tertiary epilepsy service and retrospectively reviewed medical
      records, clinical investigations, neuroimaging, and available video footage. We
      administered a telephone-based questionnaire regarding the functional impact of
      the movement disorders and perceived efficacy of treatment to the caregivers of
      one cohort of participants. RESULTS: We identified 28 patients with FOXG1
      mutations, of whom 6 had previously unreported mutations. A wide variety of
      movement disorders were identified, with dystonia, choreoathetosis, and
      orolingual/facial dyskinesias most commonly present. Ninety-three percent of
      patients had a mixed movement disorder phenotype. In contrast to the phenotype
      classically described with FOXG1 mutations, 4 patients with missense mutations
      had a milder phenotype, with independent ambulation, spoken language, and
      normocephaly. Hyperkinetic involuntary movements were a major clinical feature in
      these patients. Of the symptomatic treatments targeted to control abnormal
      involuntary movements, most did not emerge as clearly beneficial, although 4
      patients had a caregiver-reported response to levodopa. CONCLUSIONS: Abnormal
      involuntary movements are a major feature of FOXG1 mutations. Our study
      delineates the spectrum of movement disorders and confirms an expanding clinical
      phenotype. Symptomatic treatment may be considered for severe or disabling cases,
      although further research regarding potential treatment strategies is necessary.

PMID- 27029632
TI  - Abeta-related memory decline in APOE epsilon4 noncarriers: Implications for
      Alzheimer disease.
AB  - OBJECTIVE: As the absence of Abeta-related memory decline in APOE epsilon4
      noncarriers may be due to the relative brevity of previous studies, we aimed to
      characterize Abeta-related cognitive decline over 72 months in APOE epsilon4
      carriers and noncarriers who were cognitively normal (CN). METHODS: CN older
      adults (n = 423) underwent Abeta imaging and APOE genotyping. Participants
      completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and
      72-month assessments. RESULTS: Relative to Abeta- CN epsilon4 noncarriers, both
      Abeta+ CN epsilon4 carriers and noncarriers showed significantly increased
      decline in measures of memory, language, and executive function as well as higher
      rates of progression to a clinical classification of mild cognitive impairment.
      Memory decline was greater in Abeta+ CN epsilon4 carriers than in Abeta+ CN
      epsilon4 noncarriers. No cognitive decline was evident in Abeta- CN epsilon4
      carriers. CONCLUSIONS: In CN older adults, Abeta+ is associated with memory
      decline in epsilon4 noncarriers; however, the rate of this decline is much slower
      than that observed in epsilon4 carriers. These data indicate that the processes
      by which epsilon4 carriage increases the rate of Abeta-related cognitive decline
      occur in the preclinical stage of Alzheimer disease.

PMID- 27029633
TI  - Progressive diffuse meningioangiomatosis: Response to bevacizumab treatment.

PMID- 27029634
TI  - Validity and feasibility of the EMG direct observation tool (EMG-DOT).
AB  - OBJECTIVE: To develop a new workplace-based EMG direct observation tool (EMG-DOT)
      and gather validity evidence supporting its use for assessing electrodiagnostic
      skills among postgraduate medical trainees. METHODS: The EMG-DOT was developed by
      experts using an iterative process. Validity evidence from content, response
      process, internal structure, relations to other variables, and consequences of
      testing was collected during the 2013-2014 academic year. RESULTS: Of 3,412
      studies performed by trainees during the study period, 299 (9%) were assessed
      using the EMG-DOT. Of these, 203 (68%) involved a physician rater and 96 (32%)
      involved a technician rater. The 14-item EMG-DOT had excellent internal
      consistency reliability (Cronbach alpha 0.94). Correlations between individual
      items and criterion-referenced global ratings of performance ranged from 0.36 to
      0.72 (all p < 0.001). Mean total scores increased from 70% to 80% over 4 months
      of the EMG rotation (p < 0.001) despite a corresponding significant increase in
      case complexity (0.21-0.74 on a 3-point rating scale; p < 0.001). Trainees
      reported that the observational assessment exercise improved their knowledge or
      skills in 82% of encounters (188/230) and that feedback generated by the EMG-DOT
      improved the quality of care provided to patients in 58% (133/230). Trainees were
      "satisfied" or "very satisfied" with the observational assessment exercise in 96%
      of encounters (234/243). CONCLUSIONS: This study provides validity evidence
      supporting the use of EMG-DOT scores to assess electrodiagnostic skills of
      residents and fellows. The EMG-DOT can be used to inform milestone-based
      assessments of trainee performance in neurology, child neurology, physical
      medicine and rehabilitation, neuromuscular, and clinical neurophysiology training
      programs.

PMID- 27029635
TI  - Ventral tegmental area deep brain stimulation for refractory chronic cluster
      headache.
AB  - OBJECTIVE: To present outcomes in a cohort of medically intractable chronic
      cluster headache (CCH) patients treated with ventral tegmental area (VTA) deep
      brain stimulation (DBS). METHODS: In an uncontrolled open-label prospective
      study, 21 patients (17 male; mean age 52 years) with medically refractory CCH
      were selected for ipsilateral VTA-DBS by a specialist multidisciplinary team
      including a headache neurologist and functional neurosurgeon. Patients had also
      failed or were denied access to occipital nerve stimulation within the UK
      National Health Service. The primary endpoint was improvement in the headache
      frequency. Secondary outcomes included other headache scores (severity, duration,
      headache load), medication use, disability and affective scores, quality of life
      (QoL) measures, and adverse events. RESULTS: Median follow-up was 18 months
      (range 4-60 months). At the final follow-up point, there was 60% improvement in
      headache frequency (p = 0.007) and 30% improvement in headache severity (p =
      0.001). The headache load (a composite score encompassing frequency, severity,
      and duration of attacks) improved by 68% (p = 0.002). Total monthly triptan
      intake of the group dropped by 57% posttreatment. Significant improvement was
      observed in a number of QoL, disability, and mood scales. Side effects included
      diplopia, which resolved in 2 patients following stimulation adjustment, and
      persisted in 1 patient with a history of ipsilateral trochlear nerve palsy. There
      were no other serious adverse events. CONCLUSIONS: This study supports that VTA
      DBS may be a safe and effective therapy for refractory CCH patients who failed
      conventional treatments. CLASSIFICATION OF EVIDENCE: This study provides Class IV
      evidence that VTA-DBS decreases headache frequency, severity, and headache load
      in patients with medically intractable chronic cluster headaches.

PMID- 27029636
TI  - Obesity and overweight as CAE comorbidities and differential drug response
      modifiers.
AB  - OBJECTIVE: This study examined whether overweight and obesity are pretreatment
      comorbidities and predictors of short-term drug response in newly diagnosed
      untreated childhood absence epilepsy (CAE). We also examined whether dietary
      intake accounts for observed pretreatment body mass index (BMI) distribution.
      METHODS: Pretreatment height and weight were available for 445 of 446
      participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452).
      Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary
      intake were standardized for age, sex, and race/ethnicity and compared to age
      matched US population from the National Health and Nutrition Examination Survey
      (NHANES). Logistic regression models tested BMI as a predictor of treatment
      response. Pharmacokinetic variables were explored as contributors to differential
      drug response. RESULTS: After standardizing for demographic differences, children
      with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese
      (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of
      overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p <
      0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily
      carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE
      group than in NHANES controls. With increasing baseline BMI z score, the efficacy
      and effectiveness of ethosuximide and valproic acid over lamotrigine became more
      pronounced, despite no significant differences in drug exposure and trough
      levels. CONCLUSIONS: Overweight and obesity are more prevalent in children with
      newly diagnosed CAE than in age-matched peers, despite lower caloric and
      carbohydrate intake. Baseline BMI may also predict differential drug response,
      which cannot be attributed to pharmacokinetic differences.

PMID- 27029638
TI  - Two-stage total hip arthroplasty for patients with advanced active tuberculosis
      of the hip.
AB  - BACKGROUND: Treatment of advanced active tuberculosis (TB) of the hip is
      confronted with great challenges. Although one-stage total hip arthroplasty (THA)
      is considered as a safe procedure for most patients by some authors, there are
      still exceptions. The purpose of this paper was to investigate the feasibility
      and effectiveness of two-stage THA for selected patients with advanced active TB
      of the hip. METHODS: Nine consecutive patients with advanced active tuberculous
      arthritis of the hip were reviewed in this study. Out of these nine patients, the
      hips of five were destroyed extensively with difficulties of thorough debridement
      at one operation, and the hips of the other four were detected of sinus tracts.
      Nine patients received the two-stage total hip arthroplasty (THA) protocol and
      the perioperative antituberculous medication between January 2008 and December
      2013. During the first stage, a debridement was carried out after at least 2
      weeks of antituberculous chemotherapy to remove abscesses and infected and
      necrotic tissues as thoroughly as possible, followed by antituberculous
      chemotherapy for a minimum of 3 months (average 4.2 months). During the second
      stage, hip prosthesis was implanted if the erythrocyte sedimentation rate (ESR)
      and the C-reactive protein (CRP) were normal and the wound was well healed.
      Antituberculous chemotherapy was continued for 6-9 months postoperatively to
      constitute a total duration of a minimum of 12 months after the first operation.
      The patients were then evaluated based on the reactivation of infection, the
      Harris hip score system, X-ray, ESR, and CRP. RESULTS: The average follow-up was
      40 months (range, 18-72 months). No reactivation of TB or superimposed infection
      was observed in all patients. The ESR and CRP returned to the normal level with
      no liver injury. The average Harris hip score was increased from 35 (range, 15
      55) preoperatively to 91.5 (range, 83-97) at the final follow-up. The X-ray film
      showed no prosthesis shift or loosening. CONCLUSIONS: Two-stage THA is an
      alternative treatment option for patients with advanced active tuberculosis of
      the hip under some difficult conditions. The hip with sinus tracts or destroyed
      extensively with difficulties of thorough debridement at one operation may be
      regarded as indications.

PMID- 27029637
TI  - An integrated analysis tool for analyzing hybridization intensities and genotypes
      using new-generation population-optimized human arrays.
AB  - BACKGROUND: Affymetrix Axiom single nucleotide polymorphism (SNP) arrays provide
      a cost-effective, high-density, and high-throughput genotyping solution for
      population-optimized analyses. However, no public software is available for the
      integrated genomic analysis of hybridization intensities and genotypes for this
      new-generation population-optimized genotyping platform. RESULTS: A set of
      statistical methods was developed for an integrated analysis of allele frequency
      (AF), allelic imbalance (AI), loss of heterozygosity (LOH), long contiguous
      stretch of homozygosity (LCSH), and copy number variation or alteration (CNV/CNA)
      on the basis of SNP probe hybridization intensities and genotypes. This study
      analyzed 3,236 samples that were genotyped using different SNP platforms. The
      proposed AF adjustment method considerably increased the accuracy of AF
      estimation. The proposed quick circular binary segmentation algorithm for
      segmenting copy number reduced the computation time of the original segmentation
      method by 30-67 %. The proposed CNV/CNA detection, which integrates AI and
      LOH/LCSH detection, had a promising true positive rate and well-controlled false
      positive rate in simulation studies. Moreover, our real-time quantitative
      polymerase chain reaction experiments successfully validated the CNVs/CNAs that
      were identified in the Axiom data analyses using the proposed methods; some of
      the validated CNVs/CNAs were not detected in the Affymetrix Array 6.0 data
      analysis using the Affymetrix Genotyping Console. All the analysis functions are
      packaged into the ALICE (AF/LOH/LCSH/AI/CNV/CNA Enterprise) software.
      CONCLUSIONS: ALICE and the used genomic reference databases, which can be
      downloaded from http://hcyang.stat.sinica.edu.tw/software/ALICE.html , are useful
      resources for analyzing genomic data from the Axiom and other SNP arrays.

PMID- 27029640
TI  - Nursing Students' Attitudes and Intention to Work with Mentally Ill Patients
      Before and After a Planned Intervention.
AB  - OBJECTIVES: The authors examined changes in attitudes and intention to work with
      mentally ill patients (treat, specialize, or work in the field) among nursing
      students after a planned intervention consisting of a mental health course.
      METHODS: Data were collected before and after a planned intervention. The nature
      of the intervention was educational, for third year undergraduate nursing
      students. The core intervention included lectures on mental illness, encounters
      with people coping with mental illness, simulations, and a film on coping with
      mental illness. Behavioral intention to work with mentally ill patients and three
      dimensions of nursing students' attitudes (perceived functional characteristics,
      perceived danger, and value diminution of mentally ill patients) were measured
      before and after the intervention. The post-intervention impact of the
      intervention on participants' attitudes and behavioral intention was measured.
      RESULTS: One hundred and one undergraduate third year nursing students studying
      at four nursing schools in Israel participated in the study. The planned
      intervention improved the students' attitudes towards mentally ill patients but
      did not improve their intention of working with them. Post-intervention, older
      and less religious students had more intention to work with mentally ill
      patients. Moreover, older and Jewish students held better attitudes towards the
      functional characteristics of mentally ill patients. Being older was also
      correlated with the perception of mentally ill patients as less dangerous and
      male students ascribed to them more value diminution. CONCLUSIONS: Students'
      attitudes towards mentally ill patients and their behavioral intention to work in
      the psychiatry field should be addressed during the initial training and in
      continuing education. Teaching methods should include theoretical learning on
      multicultural mental health practice concurrently with clinical placements.

PMID- 27029641
TI  - Development of the assessment for collaborative environments (ACE-15): A tool to
      measure perceptions of interprofessional "teamness".
AB  - As interprofessional education moves from classroom to clinical settings,
      assessing clinical training sites for a high level of "teamness" to ensure
      optimal learning environments is critical but often problematic ahead of student
      placement. We developed a tool (Assessment for Collaborative Environments, or
      ACE), suitable for a range of clinical settings and health professionals, that
      allows rapid assessment of a clinical practice's teamwork qualities. We collected
      evidence of tool validity including content, response process, internal
      structure, and convergent validity. Expert review and cognitive interviews
      allowed reduction of the initial 30-item tool to 15 items (the ACE-15). Data from
      192 respondents from 17 clinical professions and varied clinical settings
      (inpatient, ambulatory, urban, and rural) were used for factor analysis, which
      resulted in a single factor solution. Internal consistency reliability Cronbach's
      alpha was high at 0.91. Subgroup analysis of 121 respondents grouped by their
      clinical teams (n = 16 teams) showed a wide range of intra-team agreement. Data
      from a subsequent sample of 54 clinicians who completed the ACE-15 and a measure
      of team cohesion indicated convergent validity, with a correlation of the tools
      at r = 0.81. We conclude that the ACE-15 has acceptable psychometric properties
      and promising utility for assessing interprofessional teamness in clinical
      training sites that are settings for learners, and, in addition may be useful for
      team development. 

PMID- 27029643
TI  - Cervical and breast cancer screening participation for women with chronic
      conditions in France: results from a national health survey.
AB  - BACKGROUND: Comorbidity at the time of diagnosis is an independent prognostic
      factor for survival among women suffering from cervical or breast cancer.
      Although cancer screening practices have proven their efficacy for mortality
      reduction, little is known about adherence to screening recommendations for women
      suffering from chronic conditions. We investigated the association between eleven
      chronic conditions and adherence to cervical and breast cancer screening
      recommendations in France. METHOD: Using data from a cross-sectional national
      health survey conducted in 2008, we analyzed screening participation taking into
      account self-reported: inflammatory systemic disease, cancer, cardiovascular
      disease, chronic respiratory disease, depression, diabetes, dyslipidemia,
      hypertension, obesity, osteoarthritis and thyroid disorders. We first computed
      age-standardized screening rates among women who reported each condition. We then
      estimated the effect of having reported each condition on adherence to screening
      recommendations in logistic regression models, with adjustment for
      sociodemographic characteristics, socioeconomic position, health behaviours,
      healthcare access and healthcare use. Finally, we investigated the association
      between chronic conditions and opportunistic versus organized breast cancer
      screening using multinomial logistic regression. RESULTS: The analyses were
      conducted among 4226 women for cervical cancer screening and 2056 women for
      breast cancer screening. Most conditions studied were not associated with
      screening participation. Adherence to cervical cancer screening recommendations
      was higher for cancer survivors (OR = 1.73 [0.98-3.05]) and lower for obese women
      (OR = 0.73 [0.57-0.93]), when accounting for our complete range of screening
      determinants. Women reporting chronic respiratory disease or diabetes
      participated less in cervical cancer screening, except when adjusting for
      socioeconomic characteristics. Adherence to breast cancer screening
      recommendations was lower for obese women and women reporting diabetes, even
      after accounting for our complete range of screening determinants (OR = 0.71
      [0.52-0.96] and OR = 0.55 [0.36-0.83] respectively). The lower breast cancer
      screening participation for obese women was more pronounced for opportunistic
      than for organized screening. CONCLUSION: We identified conditions associated
      with participation in cervical and breast cancer screening, even when accounting
      for major determinants of cancer screening. Obese women participated less in
      cervical cancer screening. Obese women and women with diabetes participated less
      in mammographic screening and organized breast cancer screening seemed to
      insufficiently address barriers to participation.

PMID- 27029644
TI  - Association of polymorphisms in complement component 3 with age-related macular
      degeneration in an Iranian population.
AB  - BACKGROUND: Age related macular degeneration (AMD) is the leading cause of
      irreversible blindness in the elderly population. Inflammatory mediators play an
      important role in AMD pathogenesis and immune-related gene polymorphisms are
      shown to increase the risk. Complement system is an important mediator of the
      immunity system and several genes encoding proteins involved in this system are
      associated with susceptibility to AMD. The central element of the complement
      cascade, C3 has been a plausible candidate since its cleavage product C3a was
      found in drusen. This study was planned to evaluate the association of C3
      rs2230199 (R102G) variants with advanced type AMD in this cohort. MATERIALS AND
      METHODS: In this case-control study, 494 participants consisting of 266 AMD
      patients (187 wet AMD and 79 advanced dry AMD) and 228 samples from unrelated
      healthy controls were enrolled for evaluation. Extracted-DNA samples were
      amplified to obtain fragments including the polymorphic region. RESULTS: The
      distribution of the R102G genotypes was significantly different in the AMD
      patients compared to controls (p = 0.001).The Odds Ratio compared to CC
      individuals was 1.69 (95% CI 1.15-2.49) for GC individuals and 6.48 (95% CI1.87
      22.43) for GG individuals. The Odds Ratio compared to the C allele was 2.31 (95%
      CI 0.48-11) for the G allele. GG and GC genotypes and G allele were significantly
      associated with both types of advanced-AMD. Individuals carrying GG genotype have
      over a six-fold risk of developing AMD in comparison to those carrying the CC
      genotype in this cohort. Our meta-analysis pooled data showed that our homozygous
      individuals for GG have a higher risk of AMD compared to previous publications in
      different nations (p = 0.017). CONCLUSIONS: Our study shows C3 to be a relatively
      strong susceptibility gene for advanced-type-AMD (exudative-and-geographic
      atrophy) in an Iranian population.

PMID- 27029645
TI  - Identification of chemicals that mimic transcriptional changes associated with
      autism, brain aging and neurodegeneration.
AB  - Environmental factors, including pesticides, have been linked to autism and
      neurodegeneration risk using retrospective epidemiological studies. Here we
      sought to prospectively identify chemicals that share transcriptomic signatures
      with neurological disorders, by exposing mouse cortical neuron-enriched cultures
      to hundreds of chemicals commonly found in the environment and on food. We find
      that rotenone, a pesticide associated with Parkinson's disease risk, and certain
      fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone,
      produce transcriptional changes in vitro that are similar to those seen in brain
      samples from humans with autism, advanced age and neurodegeneration (Alzheimer's
      disease and Huntington's disease). These chemicals stimulate free radical
      production and disrupt microtubules in neurons, effects that can be reduced by
      pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane.
      Our study provides an approach to prospectively identify environmental chemicals
      that transcriptionally mimic autism and other brain disorders. 

PMID- 27029647
TI  - Virtual reality gaming in the rehabilitation of the upper extremities post
      stroke.
AB  - BACKGROUND: Occurrences of strokes often result in unilateral upper limb
      dysfunction. Dysfunctions of this nature frequently persist and can present
      chronic limitations to activities of daily living. METHODS: Research into
      applying virtual reality gaming systems to provide rehabilitation therapy have
      seen resurgence. Themes explored in stroke rehab for paretic limbs are action
      observation and imitation, versatility, intensity and repetition and preservation
      of gains. Fifteen articles were ultimately selected for review. The purpose of
      this literature review is to compare the various virtual reality gaming
      modalities in the current literature and ascertain their efficacy. RESULTS: The
      literature supports the use of virtual reality gaming rehab therapy as equivalent
      to traditional therapies or as successful augmentation to those therapies. While
      some degree of rigor was displayed in the literature, small sample sizes,
      variation in study lengths and therapy durations and unequal controls reduce
      generalizability and comparability. CONCLUSIONS: Future studies should
      incorporate larger sample sizes and post-intervention follow-up measures.

PMID- 27029646
TI  - Oligomerization as a strategy for cold adaptation: Structure and dynamics of the
      GH1 beta-glucosidase from Exiguobacterium antarcticum B7.
AB  - Psychrophilic enzymes evolved from a plethora of structural scaffolds via
      multiple molecular pathways. Elucidating their adaptive strategies is
      instrumental to understand how life can thrive in cold ecosystems and to tailor
      enzymes for biotechnological applications at low temperatures. In this work, we
      used X-ray crystallography, in solution studies and molecular dynamics
      simulations to reveal the structural basis for cold adaptation of the GH1 beta
      glucosidase from Exiguobacterium antarcticum B7. We discovered that the selective
      pressure of low temperatures favored mutations that redesigned the protein
      surface, reduced the number of salt bridges, exposed more hydrophobic regions to
      the solvent and gave rise to a tetrameric arrangement not found in mesophilic and
      thermophilic homologues. As a result, some solvent-exposed regions became more
      flexible in the cold-adapted tetramer, likely contributing to enhance enzymatic
      activity at cold environments. The tetramer stabilizes the native conformation of
      the enzyme, leading to a 10-fold higher activity compared to the disassembled
      monomers. According to phylogenetic analysis, diverse adaptive strategies to cold
      environments emerged in the GH1 family, being tetramerization an alternative, not
      a rule. These findings reveal a novel strategy for enzyme cold adaptation and
      provide a framework for the semi-rational engineering of beta-glucosidases aiming
      at cold industrial processes. 

PMID- 27029648
TI  - Lipid-laden cells differentially distributed in the aging brain are functionally
      active and correspond to distinct phenotypes.
AB  - We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging
      mice evaluating their distribution, morphology, density, functional activities
      and inflammatory phenotype. We identified LLC in meningeal, cortical and
      neurogenic brain regions. The density of cerebral LLC increased with age. LLC
      presenting small lipid droplets were visualized adjacent to blood vessels or
      deeper in the brain cortical and striatal parenchyma of aging mice. LLC with
      larger droplets were asymmetrically distributed in the cerebral ventricle walls,
      mainly located in the lateral wall. We also found that LLC in the subventricular
      region co-expressed beclin-1 or LC3, markers for autophagosome or
      autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated
      protein, suggesting lipophagic activity. Some cerebral LLC exhibited beta
      galactosidase activity indicating a senescence phenotype. Moreover, we detected
      production of the pro-inflammatory cytokine TNF-alpha in cortical PLIN(+) LLC.
      Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+)
      microglia and S100beta(+) ependymal cells expressed PLIN in the aging brain. Our
      findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may
      participate in the age-associated neuroinflammatory processes. 

PMID- 27029649
TI  - Accuracy of the Structured Medication History Assessment Tool (MedHAT) Compared
      with Recorded Real-Time Medication Use.
AB  - STUDY OBJECTIVE: Medication histories are collected to measure drug exposure in
      epidemiologic studies, to identify adverse drug events and in clinical practice.
      The objective of this study was to compare the accuracy of a structured
      medication history obtained by using the Medication History Assessment Tool
      (MedHAT) with a medication diary in which subjects recorded real-time medication
      use. DESIGN: Prospective observational study. SETTING: Outpatient research
      center. SUBJECTS: Sixty-seven adult healthy volunteers. INTERVENTIONS: Subjects
      were provided diaries to record the product name, dose quantity, and time that
      they used a prescription or nonprescription medication, supplement, or vitamin.
      After a minimum of 30 continuous days of diary use, a final interview was
      conducted, and medication history data were collected by using the MedHAT.
      MEASUREMENTS AND MAIN RESULTS: We compared the medications reported during the
      interview with the medications recorded in the diary for each day to determine
      the accuracy of the verbal history. The primary outcome was the proportion of
      matches for each day for each subject. Overall accuracy for medication use for
      the day preceding the interview was 90%, and accuracy during the 30 days
      preceding the interview was 76%. Recall was higher for subjects taking
      prescription medications, those who had more recent medication use, older
      subjects, and subjects taking a higher proportion of prescription medications.
      CONCLUSION: The MedHAT system provided relatively high accuracy for immediate
      past use and for prescription medications and may offer better accuracy than
      other methods. Medication histories are often inaccurate, however, and may
      represent an important source of misclassification in epidemiologic studies. Thus
      medication histories alone should be used cautiously when measuring associations
      between drug exposure and health outcomes.

PMID- 27029650
TI  - Multiplex congruence network of natural numbers.
AB  - Congruence theory has many applications in physical, social, biological and
      technological systems. Congruence arithmetic has been a fundamental tool for data
      security and computer algebra. However, much less attention was devoted to the
      topological features of congruence relations among natural numbers. Here, we
      explore the congruence relations in the setting of a multiplex network and unveil
      some unique and outstanding properties of the multiplex congruence network.
      Analytical results show that every layer therein is a sparse and heterogeneous
      subnetwork with a scale-free topology. Counterintuitively, every layer has an
      extremely strong controllability in spite of its scale-free structure that is
      usually difficult to control. Another amazing feature is that the controllability
      is robust against targeted attacks to critical nodes but vulnerable to random
      failures, which also differs from ordinary scale-free networks. The multi-chain
      structure with a small number of chain roots arising from each layer accounts for
      the strong controllability and the abnormal feature. The multiplex congruence
      network offers a graphical solution to the simultaneous congruences problem,
      which may have implication in cryptography based on simultaneous congruences. Our
      work also gains insight into the design of networks integrating advantages of
      both heterogeneous and homogeneous networks without inheriting their limitations.

PMID- 27029651
TI  - The Lungmotor.

PMID- 27029652
TI  - Reliability of the direct observation of procedural skills assessment tool for
      ultrasound-guided regional anaesthesia.
AB  - The Direct Observation of Procedural Skills (DOPS) form is used as a workplace
      based assessment tool in the current Australian and New Zealand College of
      Anaesthetists curriculum. The objective of this study was to evaluate the
      reliability of DOPS when used to score trainees performing ultrasound-guided
      regional anaesthesia. Reliability of an assessment tool is defined as the
      reproducibility of scores given by different assessors viewing the same trainee.
      Forty-nine anaesthetists were recruited to score two scripted videos of trainees
      performing a popliteal sciatic nerve block and an axillary brachial plexus block.
      Reliability, as measured by intraclass correlation coefficients, was -0.01 to
      0.43 for the individual items in DOPS, and 0.15 for the 'Overall Performance for
      this Procedure' item. Assessors demonstrated consistency of scoring within DOPS,
      with significant correlation of sum of individual item scores with the 'Overall
      Performance for this Procedure' item (r=0.78 to 0.80, P<0.001), and with yes
      versus no responses to the 'Was the procedure completed satisfactorily?' item
      (W=24, P=0.0004, Video 1, and W=65, P=0.003, Video 2). While DOPS demonstrated a
      good degree of internal consistency in this setting, inter-rater reliability did
      not reach levels generally recommended for formative assessment tools.
      Feasibility of the form could be improved by removing the 'Was the procedure
      completed satisfactorily?' item without loss of information.

PMID- 27029653
TI  - Learning from defects using a comprehensive management system for incident
      reports in critical care.
AB  - Incident reporting systems are often used without a structured review process,
      limiting their utility to learn from defects and compromising their impact on
      improving the healthcare system. The objective of this study is to describe the
      experience of implementing a Comprehensive Management System (CMS) for incident
      reports in the ICU. A physician-led multidisciplinary Incident Report Committee
      was created to review, analyse and manage the department incident reports. New
      protocols, policies and procedures, and other patient safety interventions were
      developed as a result. Information was disseminated to staff through multiple
      avenues. We compared the pre- and post-intervention periods for the impact on the
      number of incident reports, level of harm, time needed to close reports and
      reporting individuals. A total of 1719 incidents were studied. ICU-related
      incident reports increased from 20 to 36 incidents per 1000 patient days
      (P=0.01). After implementing the CMS, there was an increase in reporting 'no
      harm' from 14.2 to 28.1 incidents per 1000 patient days (P<0.001). There was a
      significant decrease in the time needed to close incident report after
      implementing the CMS (median of 70 days [Q1-Q3: 26-212] versus 13 days [Q1-Q3: 6
      25, P<0.001]). A physician-led multidisciplinary CMS resulted in significant
      improvement in the output of the incident reporting system. This may be important
      to enhance the effectiveness of incident reporting systems in highlighting system
      defects, increasing learning opportunities and improving patient safety.

PMID- 27029654
TI  - End-tidal sevoflurane concentration for ProSeal(TM) versus Classic(TM) laryngeal
      mask airway insertion in unpremedicated anaesthetised adult females.
AB  - The optimal end-tidal sevoflurane concentration for successful ProSealTM
      (Teleflex, Morrisville, NC, USA) laryngeal mask airway (PLMA) versus ClassicTM
      (Teleflex, Morrisville, NC, USA) laryngeal mask airway (CLMA) insertion in
      unpremedicated anaesthetised adults is unknown. We determined end-tidal
      sevoflurane concentrations for successful insertion in fifty percent of
      anaesthetised adults. This randomised, prospective, double-blind study was
      conducted in the operating theatre of a government tertiary care hospital. Forty
      four unpremedicated American Society of Anesthesiologists physical status I and
      II women with cervical carcinoma (aged 30 to 60 years), scheduled for intracavity
      caesium implantation under general anaesthesia with a laryngeal mask airway (LMA)
      were included in the study. The participants were randomised to one of the two
      groups, to receive either a PLMA or CLMA. After anaesthetic induction with
      sevoflurane, a predetermined end-tidal sevoflurane concentration (starting at
      2.5%) was sustained for 10 minutes before LMA insertion was attempted. End-tidal
      sevoflurane concentration was increased/decreased (step-size 0.25%) using Dixon
      and Massey's up-and-down method for the next patient based on the previous
      patient's response. Placement without clenching, movement, coughing or biting
      within one minute was considered successful insertion. The end-tidal sevoflurane
      concentration required for successful LMA insertion in fifty percent of
      anaesthetised adults was calculated as the mean of the crossover pairs' midpoints
      in each group and further confirmed by probit regression analysis. The end-tidal
      sevoflurane concentration (95% confidence interval) required for successful PLMA
      insertion in 50% of anaesthetised adults (3.15% [3.12% to 3.18%]) was
      significantly higher than that for CLMA insertion (2.71% [2.66% to 2.76%],
      P<0.001). These findings suggest that deeper anaesthesia is required for
      placement of a PLMA in comparison to a CLMA.

PMID- 27029655
TI  - Risk factors for bleeding complications after percutaneous dilatational
      tracheostomy: a ten-year institutional analysis.
AB  - Bleeding complications after percutaneous dilatational tracheostomy (PDT) are
      infrequent but may have a tremendous impact on a patient's further clinical
      course. Therefore, it seems necessary to perform risk stratification for patients
      scheduled for PDT. We retrospectively reviewed the records of 1001 patients (46%
      male, mean age 68.1 years) undergoing PDT (using the Ciaglia Blue Rhino(r)
      technique with direct bronchoscopic guidance) in our cardiothoracic ICU between
      January 2003 and February 2013. Patients were stratified into two groups:
      patients suffering acute moderate, severe, or major bleeding (Group A) and
      patients who had no or only mild bleeding (Group B). In the majority of patients,
      no or only mild bleeding during PDT occurred (none: 425 [42.5%], mild: 488
      [48.8%]). In 84 patients (8.4%), bleeding was classified as moderate. Three
      patients suffered from severe bleeding; only one major bleed with need for
      emergency surgery occured. Patients in Group A had a significantly higher
      Simplified Acute Physiology Score on the day of PDT (P=0.042), higher prevalence
      of renal replacement therapy on the day of PDT (P=0.026), higher incidence of
      coagulopathy (P=0.043), lower platelet counts (P=0.037), lower fibrinogen levels
      (P=0.012), higher proportion of PDTs performed by residents (P=0.034) and higher
      difficulty grading of PDT (P=0.001). Using logistic regression analyses,
      difficult PDT, less experienced operator, Simplified Acute Physiology Score>40
      and low fibrinogen levels were independent predictors of clinically significant
      bleeding after PDT. Low fibrinogen levels, as well as difficult PDT, less
      experienced operator and Simplified Acute Physiology Score>40 are associated with
      an increased risk for bleeding during PDT.

PMID- 27029656
TI  - The anaesthetic assessment, management and risk factors of bariatric surgical
      patients requiring postoperative intensive care support: a state-wide, five-year
      cohort study.
AB  - Bariatric surgery is a rapidly growing and dynamic discipline necessitating a
      specialised anaesthetic approach coordinating high-risk patients with appropriate
      post-operative intensive care (ICU) support. The relationship between the
      anaesthetic and ICU utilisation after bariatric surgery is poorly understood. All
      adult bariatric surgery patients admitted to any ICU over a five-year period
      between 2007 and 2011 in Western Australia were identified from hospital
      admission records and cross-referenced against the Western Australian Department
      of Health Data Linkage Unit database. During the study period 12,062 patients
      under went bariatric surgery with 581 (4.8%) patients admitted to ICU immediately
      following surgery. The mean pre-operative ASA score was 3.3 [standard deviation
      1.1] with 76.9% of patients were assessed by their anaesthetist for the first
      time on the day-of-surgery. Blood pathology (75%) and ECG (46.3%) were the most
      common preoperative investigations. Intra-operatively, 2.1% of patients had a
      grade 4 intubation with only 3.4% of patients requiring a videoscopic assisted
      intubation. Despite being deemed at high risk, 23.6% of patients were managed
      with 20 gauge or smaller intravenous access. Anaesthetic complications were
      extremely uncommon (0.5% of all bariatric cases) but accounted for 9.7% of all
      postoperative ICU admissions. Smoking history, but not body-mass-index (P=0.46),
      was the only significant prognostic factor for respiratory or airway related
      anaesthetic complications (P=0.012). In summary, the anaesthesia management of
      bariatric surgery varied widely in Western Australia, with smoking as the only
      significant preoperative risk factor for respiratory or airway related
      anaesthesia complications. 

PMID- 27029657
TI  - Intensive care management of children intubated for croup: a retrospective
      analysis.
AB  - Croup remains the commonest reason for acute upper airway obstruction in
      children, yet there are scarce contemporary data of airway management in those
      requiring intubation. We performed a retrospective analysis of the intensive care
      management of children intubated for croup in two quaternary Paediatric Intensive
      Care Units: Royal Children's Hospital Melbourne, Australia and Alberta Children's
      Hospital Calgary, Canada. Patients intubated for less than three days were
      compared with those intubated for greater than three days. Patients less than 10
      kg body weight were compared to those greater than 10 kg. Demographic, clinical
      and microbiological data were recorded. Seventy-seven cases of croup requiring
      intubation were identified. The median duration of intubation was 60 hours.
      Parainfluenza was the most common viral aetiology, detected in 30% of cases.
      Antibiotics were prescribed in 51% of patients. Corticosteroids were prescribed
      pre intubation in two-thirds of patients and all post intubation, with the median
      dose being prednisolone 3 mg/kg/day. Primary extubation failure occurred in 6.5%
      of patients. Neither the duration of intubation nor patient size were associated
      with extubation failure. An air leak test was performed in 69% of patients and
      poorly predicted extubation success. One non-urgent tracheostomy was performed
      and there was one death from hypoxic ischaemic encephalopathy. Endotracheal tube
      leak is poorly recorded and may not predict successful extubation. 

PMID- 27029658
TI  - Acute kidney injury following liver transplantation: a systematic review of
      published predictive models.
AB  - Acute kidney injury is a frequent postoperative complication amongst liver
      transplant recipients and is associated with increased morbidity and mortality.
      This systematic review analysed the existing predictive models, in order to
      solidify current understanding. Articles were selected for inclusion if they
      described the primary development of a clinical prediction model (either an
      algorithm or risk score) to predict AKI post liver transplantation. The database
      search yielded a total of seven studies describing the primary development of a
      prediction model or risk score for the development of AKI following liver
      transplantation. The models span thirteen years of clinical research and
      highlight a gradual change in the definitions of AKI, emphasising the need to
      employ standardised definitions for subsequent studies. Collectively, the models
      identify a diverse range of predictive factors with several common trends. They
      emphasise the impact of preoperative renal dysfunction, liver disease severity
      and aetiology, metabolic risk factors as well as intraoperative variables
      including measures of haemodynamic instability and graft quality. Although
      several of the models address postoperative parameters, their utility in
      predictive modelling seems to be of questionable relevance. The common risk
      factors identified within this systematic review provide a minimum list of
      variables, which future studies should address. Research in this area would
      benefit from prospective, multi-site studies with larger cohorts as well as the
      subsequent internal and external validation of predictive models. Ultimately, the
      ability to identify patients at high risk of post-transplant AKI may enable early
      intervention and perhaps prevention. 

PMID- 27029659
TI  - Characteristics and dying trajectories of adult hospital patients from acute care
      wards who die following review by the rapid response team.
AB  - A third of patients reviewed by rapid response teams (RRT) require end-of-life
      care. However, little is known about the characteristics and management of these
      patients following RRT review. This paper presents results of a retrospective,
      descriptive audit that explored the dying trajectory of adult ward inpatients who
      died outside of intensive care following RRT review. The study setting was a 430
      bed tertiary New Zealand hospital during 2013. RRT, inpatient databases and
      hospital notes were used to identify 100 consecutive adult inpatients who died
      subsequent to RRT review. Outcome measures included time from RRT review to
      death, place of death, pre-existing co-morbidities and frequency of medical
      review. Results demonstrated that patients were old (median 77 years, IQR 63
      85years), emergency admissions (n=100) and admitted under a medical specialty
      (n=71). All but one of the cohort had pre-existing co-morbidities (mean 3.2, SD
      1.7), almost a third (n=31) had cancer and 51% had 1-4 previous inpatient
      admissions within the previous 12 months. The mean length of stay prior to RRT
      review was 4.9 days (SD 5.5) during which patients were frequently reviewed by
      senior medical staff (mean 6.8 times, SD 6.9, range 0-44). Twenty per cent of
      patients died after their first RRT review with a further 40% receiving treatment
      limitation/palliation. Fifty-two per cent of patients had a pre-existing DNAR.
      Eighty per cent of patients died in hospital. Whilst the RRT fulfils an unmet
      need in decision-making at end of life, there is a need to understand what RRT,
      instead of ward-based or palliative care teams, offers dying patients. 

PMID- 27029660
TI  - Intravenous lipid emulsion for levobupivacaine intoxication in acidotic and
      hypoxaemic pigs.
AB  - Intravenous lipid emulsion is, in some countries, the recommended treatment for
      local anaesthetic toxicity. Systemic local anaesthetic toxicity results in
      hypoxaemia and acidosis, and whether this influences the effects of lipid therapy
      on drug concentrations and cardiovascular recovery is currently unknown. Twenty
      anaesthetised pigs were given a 3-mg/kg bolus of levobupivacaine followed by a
      five minute phase of hypoventilation and 1 mmol/kg of lactic acid in one minute.
      After lactic acid infusion, pigs were treated, in randomised order, with either
      20% lipid emulsion or Ringer's acetate for 30 min: a 1.5-ml/kg bolus followed by
      a 0.25-ml/kg/minute infusion. Haemodynamic parameters were recorded and blood
      samples were collected for pharmacokinetic analysis. There was no difference
      between the groups in the area under the plasma levobupivacaine concentration
      time curve (AUC) or between that and AUC of unentrapped levobupivacaine in the
      Lipid group, or in the plasma half-lives. The cardiovascular outcome and
      normalisation of the electrocardiogram were similar in both groups. Five pigs
      developed marked hypotension: one in both groups died, while two in the Lipid
      group and one in the Ringer group needed adrenaline. Administration of lipid
      emulsion did not improve cardiovascular recovery from levobupivacaine toxicity
      exacerbated by acidosis and hypoxaemia. Lipid emulsion did not entrap
      levobupivacaine or affect levobupivacaine pharmacokinetics. 

PMID- 27029661
TI  - The effect of adjuvant remifentanil with propofol or thiopentone on seizure
      quality during electroconvulsive therapy.
AB  - In order to optimise outcome to Electro Convulsive therapy (ECT), there has been
      a trend to utilise remifentanil as an adjunct to standard intravenous induction
      agents. This has allowed a reduction in the dose of anaesthetic agent, and
      usually an improved response to stimulation. However there have been no previous
      studies to ascertain whether this improvement is simply as a result of the
      reduced dose of anaesthetic agent or whether remifentanil itself might possess
      epileptogenic properties. This retrospective case-controlled study examined ECT
      outcomes, determined by EEG quality analysis, in patients who received ECT with
      or without remifentanil, where there was no dose reduction in the anaesthetic
      agent. There were no improvements seen in the measurements of any EEG parameter,
      including seizure duration. These observations suggest that remifentanil does not
      possess any intrinsic pro-convulsant activity and that any improvement in outcome
      seen with its use is as a result of dose reduction in the IV anaesthetic agent. 

PMID- 27029662
TI  - Chewing gum in the preoperative fasting period: an analysis of de-identified
      incidents reported to webAIRS.
AB  - The role of preoperative fasting is well established in current anaesthetic
      practice with different guidelines for clear fluids and food. However, chewing
      gum may not be categorised as either food or drink by some patients, and may not
      always be specified in instructions given to patients about preoperative fasting.
      The aim of this paper was to review anaesthesia incidents involving gum chewing
      reported to webAIRS to obtain information on the risks, if any, of gum chewing
      during the preoperative fasting period. There were nine incidents involving
      chewing gum reported between late 2009 and early 2015. There were no adverse
      outcomes from the nine incidents other than postponement of surgery in three
      cases and cancellation in one. In particular, there were no reports of aspiration
      or airway obstruction. Nevertheless, there were five cases in which the gum was
      not detected preoperatively and was found in the patient's mouth either
      intraoperatively or postoperatively. These cases of undetected gum occurred
      despite patient and staff compliance with their current preoperative checklists.
      While the risk of increased gastric secretions related to chewing gum
      preoperatively are not known, the potential for airway obstruction if the gum is
      not detected and removed preoperatively is very real. We recommend that patients
      should be specifically advised to avoid gum chewing once fasting from clear
      fluids is commenced, and that a specific question regarding the presence of
      chewing gum should be added to all preoperative checklists. 

PMID- 27029663
TI  - Spontaneous ventilation using Propofol TCI for microlaryngoscopy in adults: a
      retrospective audit.
AB  - We conducted a retrospective audit of 285 adult elective microlaryngoscopy cases
      in our institution over a three-and-a-half year period. Conventional anaesthesia
      with intubation and mechanical ventilation was the most common technique, used in
      71% of cases. Tubeless spontaneous ventilation during total intravenous
      anaesthesia with a target-controlled infusion of propofol (SVTCI) was the most
      common alternative. Spontaneous ventilation with target-controlled infusion was
      used for 79 (27.7%) anaesthetic inductions and was continued through the
      maintenance phase for 60 patients (21.1%). Jet and intermittent ventilation were
      both used infrequently (1% each). The most common SVTCI technique since 2013
      involved adjusting the target-controlled infusion rate during induction using a
      formula we developed based on intermittently increasing the target rate, such
      that the predicted plasma concentration minus the predicted effect site
      concentration was maintained at 1 ug/ml. We found that this method maintained
      ventilation during induction more reliably than other SVTCI strategies, and was
      associated with fewer complications than other spontaneous ventilation techniques
      or mechanical ventilation: it was associated with only one (3.1%) failed
      induction and one (3.9%) episode of apnoea. Jet ventilation was associated with
      the most severe complications, including two cases of barotrauma.

PMID- 27029664
TI  - Successful treatment of hyperkalaemia with insulin therapy using a closed-loop
      glycaemic control device.

PMID- 27029665
TI  - Damage to a flexible laryngeal mask by metallic dental braces preventing removal
      of the mask.

PMID- 27029666
TI  - Ingested dental prosthesis causing significant gastrointestinal bleeding.

PMID- 27029667
TI  - Anaphylaxis to chlorhexidine in a chlorhexidine-coated central venous catheter
      during general anaesthesia.

PMID- 27029668
TI  - Septic shock due to Myroides odoratus in a medical intensive care unit patient
      with severe necrotising pancreatitis.

PMID- 27029669
TI  - Erratum.

PMID- 27029670
TI  - Assessing anaesthesia trainees at work: opportunities and challenges.

PMID- 27029672
TI  - Developments in parallel grafts for aortic arch lesions.
AB  - Due to the shortage of commercially available off the shelf aortic arch grafts
      since the last years parallel grafts or chimney grafts have played an increasing
      role in the treatment of patients with aortic arch lesions. Although there are
      still issues with type endoleaks and gutters between the chimney graft and the
      aortic stent-graft remaining. We report our results with the Medtronic thoracic
      graft in combination with long self-expanding parallel grafts, to ensure an
      overlapping zone of more than 7 cm between the different grafts. Alternatively,
      sandwich configurations are used where a direct contact between the parallel
      graft and the aortic wall is avoided. We have placed a total of 65 parallel
      grafts into supra-aortic branches. In 21 cases chimney grafts were placed into
      the carotid artery, in most cases into the left common carotid artery. In 36
      cases chimney grafts were placed into left subclavian artery. A maximum number of
      4 parallel grafts were placed for total endovascular debranching. In addition, in
      8 patients a parallel graft had to be placed into the innominate artery. There
      was a patency of 69% for all subclavian artery chimney grafts versus 73% for
      carotid artery parallel grafts. Of note is a stroke rate of 5.2% in all these
      cases. Only 2 of the patients with an occluded left subclavian artery chimney
      graft required a bypass procedure for arm claudication or ischemia. We had a
      primary type I endoleak rate of 28%. In almost 25% secondary interventions were
      required mainly to treat type I leaks, in those cases where the leak did not
      resolve spontaneously. The overall mortality rate was 3.5%. The results of
      parallel graft in the aortic arch are promising, but of major concern is still
      the high rate of type I endoleaks as well as the neurological complication rate,
      most probably due to catheter manipulation in patients with severe
      atherosclerotic arch lesions. 

PMID- 27029673
TI  - Covered stents in iliac artery occlusive disease: what is the evidence?
AB  - The last two decades have seen a revolution in the treatment of aortoiliac
      occlusive disease (AIOD). Acceptable safety and durability outcomes have now been
      realized with endovascular treatments, which is increasingly finding a place in
      the treatment of AIOD. Evolution of stent technologies and endovascular
      techniques is seeing an expansion of AIOD lesions indicated for primary
      endovascular treatment. The literature evidence basis is continuously evolving,
      and questions remain as to the optimal form of vessel treatment. Covered stents
      have been increasingly promoted for their long-term durability, particularly in
      extensive, challenging AIOD lesions. Here, we explore the seminal evidence basis
      for covered stents in the treatment of AIOD, and aim to provide a sound evidence
      based argument for their use. 

PMID- 27029671
TI  - Results of interferon-based treatments in Alaska Native and American Indian
      population with chronic hepatitis C.
AB  - BACKGROUND: There have been few reports of hepatitis C virus (HCV) treatment
      results with interferon-based regimens in indigenous populations. OBJECTIVE: To
      determine interferon-based treatment outcome among Alaska Native and American
      Indian (AN/AI) population. DESIGN: In an outcomes study of 1,379 AN/AI persons
      with chronic HCV infection from 1995 through 2013, we examined treatment results
      of 189 persons treated with standard interferon, interferon plus ribavirin,
      pegylated interferon plus ribavirin and triple therapy with a protease inhibitor.
      For individuals treated with pegylated interferon and ribavirin, the effect of
      patient characteristics on response was also examined. RESULTS: Sustained
      virologic response (SVR) with standard interferon was 16.7% (3/18) and with
      standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with
      pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46
      with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with
      genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon
      group was associated with female sex (p=0.002), estimated duration of infection
      (p=0.034) and HCV genotype (p<0.0001). There was a high discontinuation rate due
      to side effects in those treated with pegylated interferon and ribavirin for
      genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated
      interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%).
      CONCLUSIONS: We had success with pegylated interferon-based treatment of AN/AI
      people with genotypes 2 and 3. However, there were low SVR and high
      discontinuation rates for those with genotype 1.

PMID- 27029674
TI  - Autotransplantation: a viable treatment option for adolescent patients with
      significantly compromised teeth.
AB  - Autotransplantation is the technique of transplanting embedded, impacted or
      erupted teeth from one site into another in the same individual. Despite current
      scientific evidence indicating that autotransplantation has favourable long-term
      survival rates, autotransplantation is still not generally regarded as mainstream
      practice outside of Scandinavian countries. Successful autotransplantation can
      offer many advantages in a growing patient, including a normally functioning
      periodontium, proprioception and preservation of alveolar bone volume. In the
      event that the autotransplantation eventually fails, the bone and soft tissue
      conditions would still be likely to be favourable for subsequent implant
      treatment. This review article will identify and discuss the factors that
      influence case selection, the ideal timing for autotransplantation and the
      critical determinants for achieving a successful outcome. The limitations of the
      technique and alternative treatment options will also be discussed. It is hoped
      that through greater awareness and recognition by the dental profession,
      autotransplantation will become another viable treatment option in the management
      of compromised teeth in patients with significant remaining growth potential.

PMID- 27029675
TI  - Audit of immediate outcomes for MCDA twins following laser therapy for twin-twin
      transfusion syndrome at the NSW Fetal Therapy Centre.
AB  - OBJECTIVE: To audit immediate pregnancy and neonatal outcomes of selective laser
      photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion
      syndrome (TTTS) at the New South Wales Fetal Therapy Centre. METHODS:
      Retrospective cohort study of 151 TTTS cases undergoing SLPCV between July 2003
      and May 2013, evaluating procedural details, delivery and perinatal outcomes.
      RESULTS: The majority of cases were Stage III at SLPCV (56.9%), although
      proportion of Stage II SLPCV increased over time (P = 0.03). Survival to hospital
      discharge of at least one baby was 85.6% and dual survival was 52.5%. Median
      gestational age at delivery was 32.6 weeks (IQR 29.0-35.0 weeks) with a median of
      11.4 weeks (IQR 8.3-14.7) from laser to delivery. Median birthweight was 1792 g
      (IQR 1288-2233 g), with 75% of babies admitted to the nursery, predominantly
      secondary to prematurity. Immediate SLPCV complications were in utero fetal
      demise <1 week postprocedure in 27 fetuses (19.6%) and/or ruptured membranes <1
      week postprocedure in 9 fetuses (6.6%). CONCLUSIONS: This Australian series shows
      that local outcomes after SLPCV for stages II-IV TTTS remain equal to the
      international published literature and have remained stable after an initial
      learning curve. Women were more likely to be Stage II rather than III in the more
      recent years. However, this does not appear to be attributable to altered
      referral patterns.

PMID- 27029677
TI  - Development for All, Cradle to Crayons and Beyond.

PMID- 27029676
TI  - Effects of concurrent perioperative use of marbofloxacin and cimicoxib or
      carprofen in dogs.
AB  - OBJECTIVES: To investigate possible interactions visible on electroencephalogram
      recordings caused by concomitant administration of marbofloxacin and carprofen or
      cimicoxib in dogs without central nervous system disease. METHODS: Totally 21
      client-owned dogs undergoing different surgeries were included in a randomised,
      blinded, clinical study. Each dog was assigned to one of two groups treated with
      either carprofen or cimicoxib pre- and postoperatively. After anaesthetic
      induction both groups received marbofloxacin intravenously while recording an
      electroencephalogram. Offline electroencephalogram analysis included qualitative
      evaluation and Fast Fourier Transformation. Postoperative analgesia was evaluated
      for 24 hours and after 10 days with the short-form Glasgow Composite Measure Pain
      Scale. Statistical analysis included Wilcoxon signed rank test, Mann-Whitney U
      test and Student's t-test with alpha set at 5%. RESULTS: Marbofloxacin injection
      caused no effects on quantitative and qualitative electroencephalogram parameters
      in both groups. No differences in postoperative pain scoring were found between
      treatment groups. CLINICAL SIGNIFICANCE: Concurrent use of marbofloxacin with
      either cimicoxib or carprofen did not induce neuroexcitatory activities in dogs
      without CNS disease directly after administration.

PMID- 27029678
TI  - Combination of Oral Iron Chelators for Thalassemia.

PMID- 27029679
TI  - Clinical Scoring Systems and Radiologic Imaging in the Diagnosis of Pediatric
      Appendicitis.

PMID- 27029680
TI  - Crusade against Malnutrition: Nutrition Education Program.
AB  - A holistic approach in assessment and plan for intervention in childhood
      malnutrition is the need of the hour. This is in the context of nutrition
      education program (NEP), undertaken under the National IAP action plan, 2015. In
      the crusade against malnutrition, an ABCDEFQ assessment scale is recommended,
      with aspects covering anthropometric, biochemical, clinical, dietary,
      ecological/epidemiological, functional parameters and quality of life. In the
      dietary assessment, a scoring system based on the ten interventions related to
      infant and young child feeding (IYCF) practices recommended by UNICEF and the
      food frequency table score are incorporated. In the evaluation of quality of life
      and plan for intervention, a tool called IMPACT (IAP Malnutrition Proactive
      Assessment: A Comprehensive Tool) is proposed. 

PMID- 27029681
TI  - Comparative Efficacy and Safety of Oral Iron Chelators and their Novel
      Combination in Children with Thalassemia.
AB  - OBJECTIVE: To compare the efficacy and safety of oral iron chelators (Deferiprone
      and Deferasirox) when used singly and in combination in multi-transfused children
      with thalassemia. DESIGN: Prospective comparative study. SETTING: Thalassemia
      Center of a medical college affiliated hospital. PARTICIPANTS AND INTERVENTION:
      49 multi-transfused children with thalassemia with a mean (SD) age 11.6 (6.21) y
      received daily chelation therapy with either deferiprone alone (75 mg/kg/day in 3
      divided doses), deferasirox alone (30 mg/kg/day single dose) or their daily
      combination (same dose as monotherapy) for 12 months. OUTCOME MEASURES: Serum
      ferritin levels at the start of study, after 6 months and after 12 months. MRI
      T2* of liver and heart initially and after 6 months of follow up. 24-hour urinary
      iron excretion values at the outset and after 12 months of chelation therapy. At
      every visit for blood transfusion, all patients were clinically assessed for any
      adverse effects; liver and renal functions were monitored 6-monthly. RESULTS:
      After 12 months of respective chelation therapy, serum ferritin values decreased
      from a mean of 3140.5 ng/mL to 2910.0 ng/mL in deferiprone alone group, 3859.2
      ng/mL to 3417.4 ng/mL in deferasirox alone group and from 3696.5 ng/mL to 2572.1
      ng/mL in the combination group. The combination therapy was more efficacious in
      causing fall in serum ferritin levels compared to deferiprone and deferasirox
      monotherapy (P= 0.035 and 0.040, respectively). Results of MRI T2 were equivocal.
      Combined drug usage produced maximum negative iron balance in the body by
      maximally increasing the iron excretion in urine from 61.1 umol/day to 343.3
      umol/day (P = 0.002). No significant adverse reactions were noticed in either the
      monotherapy or the combination group. CONCLUSION: Oral combination therapy of
      deferiprone and deferasirox appears to be an efficacious and safe modality to
      reduce serum ferritin in multi-transfused children with thalassemia.

PMID- 27029682
TI  - ADRB2 Polymorphism and Salbutamol Responsiveness in Northern Indian Children with
      Mild to Moderate Exacerbation of Asthma.
AB  - OBJECTIVE: The primary objective was to determine the association between beta-2
      adrenergic receptor (ADRB2) gene polymorphism (rs1042713, c.46A>G, p.Arg16Gly)
      and the response to inhaled salbutamol in North Indian children aged 5 to 15
      years, with mild to moderate exacerbation of asthma. METHODS: This cross
      sectional study was done at a tertiary-care hospital in Northern India from June
      2011 to May 2013. 120 children with asthma with mild to moderate exacerbation
      underwent spirometry at baseline and after administration of three doses of
      salbutamol. An increase in FEV1 =15% was considered as positive response. Blood
      samples from these children were analysed for ADRB2 polymorphism (p.Arg16Gly). 94
      non-asthmatic adult controls were also studied to determine the prevalence of
      ADRB2 polymorphism. RESULTS: In asthmatic children, the frequency of AA, GG, AG
      genotypes were 24.2%, 24.2% and 51.7% compared to 20.2%, 20.2% and 59.6%,
      respectively in the non-asthmatic adults. Salbutamol responsiveness showed no
      correlation with the studied ADRB2 polymorphism (p= 0.55). A trend towards
      greater bronchodilator responsiveness amongst AA genotype, compared to GG
      genotype was observed (Median change in percent predicted FEV1 14.5% and 7.5%,
      respectively). CONCLUSION: No correlation was found between salbutamol
      responsiveness and ADRB2 genotype in Northern Indian children with asthma with
      mild-to moderate exacerbation.

PMID- 27029683
TI  - Use of the Pediatric Appendicitis Score in a Community Hospital.
AB  - OBJECTIVE: To suggest the use of the Pediatric appendicitis score (PAS) for
      diagnosing acute pediatric appendicitis in a community hospital. METHODS: We
      retrospectively reviewed the data of 285 patients aged 3 to 17 years who
      underwent abdominal computed tomography (CT) for suspected acute appendicitis at
      a single community hospital. The PAS score was compared with the CT findings in
      the appendicitis (n=86) and non-appendicitis (n=199) group. RESULTS: The
      appendicitis group had a significantly higher PAS and more frequently positive CT
      findings for appendicitis than the non-appendicitis group (P<0.01). There were no
      significant differences in the diagnostic performance of the PAS and CT. Patients
      with a PAS of 1 to 3 could be discharged without further imaging study, those
      with a PAS of 4 to 6 might need to undergo further imaging study, and those with
      7 to 10 PAS required surgical consultation with imaging study. CONCLUSIONS: The
      application of this score could help in reducing the reliance on CT and in
      standardizing the clinical assessment in a community hospital.

PMID- 27029684
TI  - Childhood Leprosy in an Endemic Area of Central India.
AB  - OBJECTIVE: To study clinical-epidemiological aspects of children affected with
      leprosy in a high-endemicity area. METHODS: Hospital-based study (April 2010 to
      March 2015) of newly diagnosed children (=18 years) with leprosy, from a leprosy
      research institute in Chhattisgarh, India. RESULTS: 551 new childhood cases were
      diagnosed constituting 16% of the total newly leprosy cases examined; 221 (40.1%)
      were multibacillary cases with 11.2% smear positivity. 243 (44.1%) had known
      contact history of leprosy, 17.6% of children developed Lepra reaction, and 17.4%
      had visible deformity. 68% of subjects completed treatment within the prescribed
      time. CONCLUSION: Transmission of leprosy is still continuing in the area, and
      high disability and deformity rates are seen in children.

PMID- 27029685
TI  - Bacterial Pathogens Associated with Community-acquired Pneumonia in Children Aged
      Below Five Years.
AB  - OBJECTIVE: To determine the spectrum of bacterial pathogens causing community
      acquired pneumonia in children below 5 years of age. METHODS: Children aged below
      5 years satisfying the WHO criteria for pneumonia, severe pneumonia or very
      severe pneumonia, and with the presence of lung infiltrates on chest X-ray were
      enrolled. Two respiratory samples, one for culture and the other for PCR
      analysis, and a blood sample for culture were collected from every child.
      RESULTS: Of the 180 samples processed, bacterial pathogens were detected in
      64.4%. Streptococcus pneumoniae and Hemophilus influenzae were most frequently
      detected. The performance of PCR analysis and culture were identical for the
      typical bacterial pathogens; atypical pathogens were detected by PCR analysis
      only. CONCLUSION: S. pneumoniae and H. influenza were the most commonly detected
      organisms from respiratory secretions of children with community acquired
      pneumonia.

PMID- 27029686
TI  - Surfactant Replacement Therapy Beyond Respiratory Distress Syndrome in Neonates.
AB  - BACKGROUND: Surfactant replacement therapy is an established modality of
      treatment in preterm neonates with respiratory distress syndrome. In addition,
      there are various neonatal respiratory disorders which are characterized by
      surfactant deficiency in which surfactant therapy can be a feasible and safe
      option. OBJECTIVE: To collate the literature on the use of surfactant replacement
      therapy in neonates beyond respiratory distress syndrome and examine the evidence
      and newer developments. SEARCH METHODS: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, and EMBASE up to
      June 2015; and previous reviews, including cross-references, abstracts, and
      conference proceedings. RESULTS: Evidence supports surfactant administration via
      bolus route in neonates with meconium aspiration syndrome, but additional robust
      evidence is required before its adoption in clinical practice. There is limited
      evidence to support surfactant therapy in neonates with pneumonia, pulmonary
      hemorrhage and bronchopulmonary dysplasia. Large multicenter randomized trials
      are needed to cement or refute the role of surfactant therapy in these disorders.

PMID- 27029687
TI  - Writing the Title, Abstract and Introduction: Looks Matter!

PMID- 27029688
TI  - Perinatal Mortality--What has Changed?

PMID- 27029689
TI  - Oral Azithromycin for Acute Episodic Airway Symptoms in Young Children: Evidence
      based Medicine Viewpoint.

PMID- 27029692
TI  - Worsening of Callus Hyperplasia after Bisphosphonate Treatment in Type V
      Osteogenesis Imperfecta.
AB  - BACKGROUND: Type V osteogenesis imperfecta is characterized by hyperplastic
      callus formation and interosseus membrane calcification. CASE CHARACTERISTICS: A
      16-year-old boy who presented with history of recurrent fractures, had hard
      persistent swellings at fracture sites, and had radiographic features of
      hyperplastic callus and interosseus membrane calcification. OUTCOME: Sequence
      analysis of the IFITM5 gene revealed the c.-14 C>T mutation. The patient had
      significant exacerbation of callus hyperplasia after initiation of bisphosphonate
      therapy, which reversed following cessation of the treatment. MESSAGE:
      Bisphosphonates may exacerbate callus hyperplasia, and may therefore have to be
      used with caution in patients with type V osteogenesis imperfecta.

PMID- 27029693
TI  - Gastrointestinal Fistulization in Amebic Liver Abscess.
AB  - BACKGROUND: Liver abscess is a common deep seated abscess in children; amebic
      liver abscess is associated with more local complications. CASE CHARACTERISTICS:
      We report two preschool children presenting with short history of pain, fever and
      right upper quadrant pain. The abscess communicated with gastro-intestinal tract
      (ascending colon in case 1 and duodenum in case 2), and diagnosis of amebic liver
      abscess was confirmed by DNA PCR. OUTCOME: Both children were successfully
      managed with intravenous antibiotics and catheter drainage. MESSAGE:
      Gastrointestinal fistulization may be rarely seen in amebic liver abscess.
      Conservative management with antibiotics, catheter drainage and supportive care
      may suffice.

PMID- 27029694
TI  - Vitamin B12 Status of Mothers of Children with Infantile Tremor Syndrome.
AB  - Retrospective chart review of 15 patients with infantile tremor syndrome in which
      mothers had their serum vitamin B12 measured, showed low (<200 pg/mL) serum
      vitamin B12 in 9 and low-normal (<200-350 pg/mL) in 6. Of the 9 mothers who had
      undergone complete blood counts, anemia was present in 6 and macrocytosis in 3.
      Vitamin B12 deficiency appears to be common in mothers of infants with infantile
      tremor syndrome. 

PMID- 27029695
TI  - Language Evaluation Scale Trivandrum (LEST 3-6 years) Development and Validation.
AB  - Language Evaluation Scale Trivandrum (LEST:3-6 years) with 31-items, was
      validated against extended REELS with a community sample-606 children (3-6yrs).
      One item and two item delay as LEST delay showed a sensitivity of (81%, 47%);
      specificity (68%, 94%), PPV (12%, 31%); NPV (98%, 97%) and accuracy (68.5%, 92%),
      respectively. LEST (3-6years) is a simple, valid, community screening tool. 

PMID- 27029696
TI  - Developmental Dysplasia of Spastic Hip in Children with Cerebral Palsy in
      Southern India.
AB  - We studied the proportion of developmental dysplasia of spastic hip in children
      with cerebral palsy. Children with cerebral palsy aged 2-12 years were enrolled.
      Migration percentage was measured on pelvic radiographs. Hip dysplasia was seen
      in 15 (12.7%) children. 

PMID- 27029697
TI  - Biologicals in Juvenile Idiopathic Arthritis.
AB  - We share our experience with biological agents in children with juvenile
      idiopathic arthritis with an aim to highlight the adverse events and response to
      treatment. Out of a total of 10 children treated with biological agents, one
      patient had serious infection, all showed good response and none had
      tuberculosis. High cost was limiting factor for their use. 

PMID- 27029698
TI  - A Novel Missense Mutation in Very Long-chain Acyl-CoA Dehydrogenase Deficiency.

PMID- 27029699
TI  - Pulsus Paradoxus in a Neonate with Interrupted Aortic Arch.

PMID- 27029700
TI  - Leaving Against Medical Advice: Underestimated Challenge in Children.

PMID- 27029701
TI  - Chemical Burn in a Neonate.

PMID- 27029702
TI  - Congenital Varicella Syndrome.

PMID- 27029703
TI  - Reply to the letter to the editor 'What is the clinical impact of the LUX-Lung 5
      trial?' by Addeo.

PMID- 27029704
TI  - Quality of life with palbociclib plus fulvestrant in previously treated hormone
      receptor-positive, HER2-negative metastatic breast cancer: patient-reported
      outcomes from the PALOMA-3 trial.
AB  - BACKGROUND: In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated
      improved progression-free survival compared with fulvestrant plus placebo in
      hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer
      (MBC). This analysis compared patient-reported outcomes (PROs) between the two
      treatment groups. PATIENTS AND METHODS: Patients were randomized 2 : 1 to receive
      palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus
      fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n =
      174). PROs were assessed on day 1 of cycles 1-4 and of every other subsequent
      cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module,
      QLQ-BR23. High scores (range 0-100) could indicate better functioning/quality of
      life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses
      were carried out to compare on-treatment overall scores and changes from baseline
      between treatment groups while controlling for baseline. Between-group
      comparisons of time to deterioration in global QoL and pain were made using an
      unstratified log-rank test and Cox proportional hazards model. RESULTS:
      Questionnaire completion rates were high at baseline and during treatment (from
      baseline to cycle 14, >=95.8% in each group completed >=1 question on the EORTC
      QLQ-C30). On treatment, estimated overall global QoL scores significantly favored
      the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5
      67.7 versus 63.0, 95% CI 60.6-65.3; P = 0.0313]. Significantly greater
      improvement from baseline in pain was also observed in this group (-3.3, 95% CI 
      5.1 to -1.5 versus 2.0, 95% CI -0.6 to 4.6; P = 0.0011). No significant
      differences were observed for other QLQ-BR23 functioning domains, breast or arm
      symptoms. Treatment with palbociclib plus fulvestrant significantly delayed
      deterioration in global QoL (P < 0.025) and pain (P < 0.001) compared with
      fulvestrant alone. CONCLUSION: Palbociclib plus fulvestrant allowed patients to
      maintain good QoL in the endocrine resistance setting while experiencing
      substantially delayed disease progression. CLINICAL TRIAL REGISTRATION:
      NCT01942135.

PMID- 27029705
TI  - Activity of immune checkpoint inhibition in platinum refractory germ-cell tumors.

PMID- 27029706
TI  - Health-related quality of life in women with recurrent ovarian cancer receiving
      paclitaxel plus trebananib or placebo (TRINOVA-1).
AB  - BACKGROUND: To evaluate the influence of treatment on health-related quality of
      life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1
      study, a randomized, placebo-controlled phase III study that demonstrated that
      trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression
      free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4
      months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P < 0.001).
      PATIENTS AND METHODS: HRQoL was assessed with the Functional Assessment of Cancer
      Therapy-Ovary [FACT-O; comprising FACT-G and the ovarian cancer-specific subscale
      (OCS)] and EuroQOL EQ-5D instruments before treatment on day 1 of weeks 1, 5, 9,
      13, 17, and every 8 weeks thereafter and at the safety follow-up visit. A pattern
      mixture model was used to evaluate the influence of patient dropout on FACT-O and
      OCS scores over time. RESULTS: Of 919 randomized patients, 834 (91%) had a
      baseline and >=1 post-baseline HRQoL assessment. At baseline, scores for all
      instruments were similar for both arms. At 25 weeks, mean +/- SD changes from
      baseline were negligible, with mean +/- SD changes typically <1 unit from
      baseline: -2.4 +/- 16.6 in the trebananib arm and -1.6 +/- 15.2 in the placebo
      arm for FACT-O, -0.71 +/- 5.5 in the trebananib arm and -0.86 +/- 4.9 in the
      placebo arm for OCS, and -0.02 +/- 0.22 in the trebananib arm and 0.02 +/- 0.19
      in the placebo arm for EQ-5D. Distribution of scores was similar between
      treatment arms at baseline and over the course of the study. In pattern-mixture
      models, there was no evidence that patient dropout affected differences in mean
      FACT-O or OCS scores. Edema had limited effect on either FACT-O or OCS scores in
      patients with grade >=2 edema or those with grade 1 or no edema. CONCLUSIONS: Our
      results demonstrate that the improvement in PFS among patients in the trebananib
      arm in the TRINOVA-1 study was achieved without compromising HRQoL.
      CLINICALTRIALSGOV IDENTIFIER: NCT01204749.

PMID- 27029707
TI  - Impact of a tailored oral vitamin D supplementation regimen on serum 25
      hydroxyvitamin D levels in early breast cancer patients: a randomized phase III
      study.
AB  - BACKGROUND: A minority of early breast cancer (EBC) patients treated with
      adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD)
      level. This randomized phase III study assessed the safety and efficacy of a
      tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy
      vitD (25OHD) level in this population. PATIENTS AND METHODS: Participants
      received a 6-month conventional (C) vitD and calcium supplementation or a 6-month
      high-dose oral vitD regimen tailored on the deficiency (T) and a conventional
      calcium supplementation. The primary end point was the 6-month percentage of
      25OHD serum level normalization. RESULTS: A total of 215 patients including 197
      patients with vitD deficiency were recruited, and 195 patients were randomized
      (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67%
      in the C and T arms, respectively. Discontinuous high-dose vitD compliance
      appeared higher in the T arm (77%). At 6 months, more patients presented with a
      normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation
      was well tolerated, and no significant difference in the treatment-related
      toxicity between the two arms was reported. Fifty-two patients without vitD
      normalization from the C arm switched to the T arm after 6 months. At 12 months,
      44% of these patients achieved vitD normalization. CONCLUSION: A tailored high
      dose oral vitD supplementation safely allows a higher percentage of the serum
      25OHD level normalization compared with a conventional regimen in chemotherapy
      treated EBC patients. As compliance to a daily oral supplementation remains poor
      in this setting, an adaptation of the treatment schedule is warranted. CLINICAL
      TRIAL NUMBER: NCT01480869.

PMID- 27029709
TI  - Pragmatic randomized clinical trials: a proposal to enhance evaluation of new
      cancer therapies with early signs of exceptional activity.

PMID- 27029708
TI  - Primary analysis of a prospective, randomized, single-blinded phase II trial
      evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent
      recurrence.
AB  - BACKGROUND: AE37 is the Ii-Key hybrid of the MHC class II peptide, AE36 (HER2
      aa:776-790). Phase I studies showed AE37 administered with granulocyte macrophage
      colony-stimulating factor (GM-CSF) to be safe and highly immunogenic. A
      prospective, randomized, multicenter phase II adjuvant trial was conducted to
      evaluate the vaccine's efficacy. METHODS: Clinically disease-free node-positive
      and high-risk node-negative breast cancer patients with tumors expressing any
      degree of HER2 [immunohistochemistry (IHC) 1-3+] were enrolled. Patients were
      randomized to AE37 + GM-CSF versus GM-CSF alone. Toxicity was monitored. Clinical
      recurrences were documented and disease-free survival (DFS) analyzed. RESULTS:
      The trial enrolled 298 patients; 153 received AE37 + GM-CSF and 145 received GM
      CSF alone. The groups were well matched for clinicopathologic characteristics.
      Toxicities have been minimal. At the time of the primary analysis, the recurrence
      rate in the vaccinated group was 12.4% versus 13.8% in the control group
      [relative risk reduction 12%, HR 0.885, 95% confidence interval (CI) 0.472-1.659,
      P = 0.70]. The Kaplan-Meier estimated 5-year DFS rate was 80.8% in vaccinated
      versus 79.5% in control patients. In planned subset analyses of patients with IHC
      1+/2+ HER2-expressing tumors, 5-year DFS was 77.2% in vaccinated patients (n =
      76) versus 65.7% in control patients (n = 78) (P = 0.21). In patients with triple
      negative breast cancer (HER2 IHC 1+/2+ and hormone receptor negative) DFS was
      77.7% in vaccinated patients (n = 25) versus 49.0% in control patients (n = 25)
      (P = 0.12). CONCLUSION: The overall intention-to-treat analysis demonstrates no
      benefit to vaccination. However, the results confirm that the vaccine is safe and
      suggest that vaccination may have clinical benefit in patients with low HER2
      expressing tumors, specifically TNBC. Further evaluation in a randomized trial
      enrolling TNBC patients is warranted.

PMID- 27029711
TI  - Disulfiram neuropathy: two case reports.
AB  - BACKGROUND: Neuropathy is a rare adverse side effect of disulfiram therapy and is
      under-recognized. There have been few case reports documenting this side effect.
      CASE PRESENTATION: Two cases of disulfiram peripheral neuropathy are discussed.
      The first case is that of a 25-year-old Caucasian woman who was exposed to
      disulfiram therapy for a total of 8 months and developed pain and stiffness that
      prevented her from walking. The second case is that of a 46-year-old Caucasian
      woman who developed sudden-onset numbness in her lower extremities with
      progression to pain. Her symptoms improved over the course of 2 months after
      cessation of disulfiram therapy. In both cases, symptoms improved after cessation
      of disulfiram therapy. CONCLUSIONS: Disulfiram neuropathy occurs in persons with
      a history of chronic alcohol use. It is under-recognized and often attributed to
      alcoholic neuropathy given its comorbidity with alcoholic neuropathy. A greater
      understanding of this side effect may reduce neurologic complications related to
      disulfiram neuropathy and aid in early withdrawal of this offending agent.

PMID- 27029710
TI  - A genomic case study of mixed fibrolamellar hepatocellular carcinoma.
AB  - BACKGROUND: Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is a rare
      liver tumor defined by the presence of both pure FL-HCC and conventional HCC
      components, represents up to 25% of cases of FL-HCC, and has been associated with
      worse prognosis. Recent genomic characterization of pure FL-HCC identified a
      highly recurrent transcript fusion (DNAJB1:PRKACA) not found in conventional HCC.
      PATIENTS AND METHODS: We performed exome and transcriptome sequencing of a case
      of mFL-HCC. A novel BAC-capture approach was developed to identify a 400 kb
      deletion as the underlying genomic mechanism for a DNAJB1:PRKACA fusion in this
      case. A sensitive Nanostring Elements assay was used to screen for this
      transcript fusion in a second case of mFL-HCC, 112 additional HCC samples and 44
      adjacent non-tumor liver samples. RESULTS: We report the first comprehensive
      genomic analysis of a case of mFL-HCC. No common HCC-associated mutations were
      identified. The very low mutation rate of this case, large number of mostly
      single-copy, long-range copy number variants, and high expression of ERBB2 were
      more consistent with previous reports of pure FL-HCC than conventional HCC. In
      particular, the DNAJB1:PRKACA fusion transcript specifically associated with pure
      FL-HCC was detected at very high expression levels. Subsequent analysis revealed
      the presence of this fusion in all primary and metastatic samples, including
      those with mixed or conventional HCC pathology. A second case of mFL-HCC
      confirmed our finding that the fusion was detectable in conventional components.
      An expanded screen identified a third case of fusion-positive HCC, which upon
      review, also had both conventional and fibrolamellar features. This screen
      confirmed the absence of the fusion in all conventional HCC and adjacent non
      tumor liver samples. CONCLUSION: These results indicate that mFL-HCC is similar
      to pure FL-HCC at the genomic level and the DNAJB1:PRKACA fusion can be used as a
      diagnostic tool for both pure and mFL-HCC.

PMID- 27029713
TI  - Predicting the responses of forest distribution and aboveground biomass to
      climate change under RCP scenarios in southern China.
AB  - In the past three decades, our global climate has been experiencing unprecedented
      warming. This warming has and will continue to significantly influence the
      structure and function of forest ecosystems. While studies have been conducted to
      explore the possible responses of forest landscapes to future climate change, the
      representative concentration pathways (RCPs) scenarios under the framework of the
      Coupled Model Intercomparison Project Phase 5 (CMIP5) have not been widely used
      in quantitative modeling research of forest landscapes. We used LANDIS-II, a
      forest dynamic landscape model, coupled with a forest ecosystem process model
      (PnET-II), to simulate spatial interactions and ecological succession processes
      under RCP scenarios, RCP2.6, RCP4.5 and RCP8.5, respectively. We also modeled a
      control scenario of extrapolating current climate conditions to examine changes
      in distribution and aboveground biomass (AGB) among five different forest types
      for the period of 2010-2100 in Taihe County in southern China, where subtropical
      coniferous plantations dominate. The results of the simulation show that climate
      change will significantly influence forest distribution and AGB. (i) Evergreen
      broad-leaved forests will expand into Chinese fir and Chinese weeping cypress
      forests. The area percentages of evergreen broad-leaved forests under RCP2.6,
      RCP4.5, RCP8.5 and the control scenarios account for 18.25%, 18.71%, 18.85% and
      17.46% of total forest area, respectively. (ii) The total AGB under RCP4.5 will
      reach its highest level by the year 2100. Compared with the control scenarios,
      the total AGB under RCP2.6, RCP4.5 and RCP8.5 increases by 24.1%, 64.2% and
      29.8%, respectively. (iii) The forest total AGB increases rapidly at first and
      then decreases slowly on the temporal dimension. (iv) Even though the fluctuation
      patterns of total AGB will remain consistent under various future climatic
      scenarios, there will be certain responsive differences among various forest
      types.

PMID- 27029712
TI  - Two host microRNAs influence WSSV replication via STAT gene regulation.
AB  - MicroRNAs (miRNAs) have important roles in post-transcriptional regulation of
      gene expression. During viral infection, viruses utilize hosts to enhance their
      replication by altering cellular miRNAs. The Janus kinase (JAK)/signal transducer
      and activator of transcription (STAT) pathway plays crucial roles in the
      antiviral responses. In this study, two miRNAs (miR-9041 and miR-9850) from
      Macrobrachium rosenbergii were found to promote white spot syndrome virus (WSSV)
      replication. The up-regulation of miR-9041 or miR-9850 suppresses STAT expression
      in the gills of M. rosenbergii, which subsequently down-regulates the expression
      of its downstream dynamin (Dnm) genes: Dnm1, Dnm2, and Dnm3. Knockdown of miR
      9041 and miR-9850 restricts WSSV replication by up-regulating STAT and Dnm gene
      expression. The silencing of STAT, Dnm1, Dnm2, or Dnm3 led to an increase of the
      number of WSSV copies in shrimp. The injection of recombinant Dnm1, Dnm2, or Dnm3
      proteins could inhibit WSSV replication in vivo. Overall, our research indicates
      the roles of host miRNAs in the enhancement of WSSV replication by regulating the
      host JAK/STAT pathway. 

PMID- 27029714
TI  - Plaque morphology predictors of side branch occlusion after provisional stenting
      in coronary bifurcation lesion: Results of optical coherence tomography
      bifurcation study (ORBID).
AB  - OBJECTIVES: The aim of this study was to identify the predictors of side branch
      (SB) ostial stenosis developed after provisional stenting of the main vessel (MV)
      using optical coherence tomography (OCT). BACKGROUND: Provisional stenting
      remains the main approach to treatment of bifurcation lesions; however, it may
      result in the narrowing of SB ostium. There is little information about
      underlying plaque morphology of the MV lesion and its potential impact on the SB
      after provisional stenting. METHODS: Patients with stable coronary disease with
      angiographic MV lesion not involving SB were included in a prospective single
      center study. The primary outcome was significant SB ostium stenosis (SBOS),
      defined as residual stenosis of >50% after MV stenting. RESULTS: Thirty
      bifurcation lesions in 30 patients were analyzed in the study. Poststenting
      significant SBOS was observed in 30% of patients. The MV lesions with SBOS > 50%
      were characterized by a higher prevalence of lipid rich plaques (100 vs. 64%, p =
      0.040) and spotty calcifications (60 vs. 0%, p = 0.005). Maximal lipid arcs were
      greater (257 degrees  vs. 132 degrees , p = 0.001) and lipid volume index was
      higher (1380 vs. 574, p = 0.012) in the SBOS >50% group. Multivariate logistic
      regression analysis identified maximal lipid arc (odds ratio (OR): 1.014, p =
      0.038) and the presence of lipid plaque contralateral to SB ostium (OR: 8.14, p =
      0.046) before stenting as independent predictors of significant SBOS after PCI.
      CONCLUSIONS: High lipid content of the MV lesion and a contralateral location of
      lipid in the bifurcation area may contribute to SBOS after provisional stenting.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27029715
TI  - Is contrast-enhanced spectral mammography (CESM) helpful in differentiating
      diabetic mastopathy from breast carcinoma?
AB  - Diabetic mastopathy (DM) is a rare benign inflammatory disease of the breast,
      which nevertheless gives suspicious image of malignancy by breast ultrasound and
      mammography. MRI studies of this disease have indicated both nonspecific
      enhancement and non-enhancement of the lesion, depending on its degree of
      lymphocytic infiltration. This is the first case report discussing the
      appearances of DM on CESM, a novel mammographic technique.

PMID- 27029717
TI  - Using the template for intervention description and replication (TIDieR) as a
      tool for improving the design and reporting of manual therapy interventions.
AB  - The detailed reporting of any research intervention is crucial to evaluate its
      applicability into a routinely practice-based context. However, it has been
      estimated that, especially in non-pharmacological interventions, the published
      literature typically includes incomplete intervention details. In the field of
      manual medicine, where interventions are delivered with a high degree of
      individualization and variability, poorly reported studies could compromise
      internal and external validity of the results. Among the various initiatives that
      have been undertaken to improve the intervention description, the Template for
      Intervention Description and Replication (TIDieR) has to be highlighted as the
      most promising. TIDieR offers both to researchers and clinicians a helpful and
      comprehensive guidance on how manual therapy interventions have to be designed
      and reported, taking into account the clinical complexity of manual therapy and
      the need to satisfy research gold standards. 

PMID- 27029716
TI  - Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive
      Dysfunction, and Cognitive Impairment in Former High School and College Football
      Players.
AB  - The term "repetitive head impacts" (RHI) refers to the cumulative exposure to
      concussive and subconcussive events. Although RHI are believed to increase risk
      for later-life neurological consequences (including chronic traumatic
      encephalopathy), quantitative analysis of this relationship has not yet been
      examined because of the lack of validated tools to quantify lifetime RHI
      exposure. The objectives of this study were: 1) to develop a metric to quantify
      cumulative RHI exposure from football, which we term the "cumulative head impact
      index" (CHII); 2) to use the CHII to examine the association between RHI exposure
      and long-term clinical outcomes; and 3) to evaluate its predictive properties
      relative to other exposure metrics (i.e., duration of play, age of first
      exposure, concussion history). Participants included 93 former high school and
      collegiate football players who completed objective cognitive and self-reported
      behavioral/mood tests as part of a larger ongoing longitudinal study. Using
      established cutoff scores, we transformed continuous outcomes into dichotomous
      variables (normal vs. impaired). The CHII was computed for each participant and
      derived from a combination of self-reported athletic history (i.e., number of
      seasons, position[s], levels played), and impact frequencies reported in helmet
      accelerometer studies. A bivariate probit, instrumental variable model revealed a
      threshold dose-response relationship between the CHII and risk for later-life
      cognitive impairment (p < 0.0001), self-reported executive dysfunction (p <
      0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral
      dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive
      validity than other individual exposure metrics.

PMID- 27029718
TI  - Type 2M von Willebrand disease - more often misidentified than correctly
      identified.
AB  - INTRODUCTION: Appropriate diagnosis of von Willebrand disease (VWD), including
      differential identification of qualitative vs. quantitative von Willebrand factor
      (VWF) defects has important management implications, but remains problematic.
      AIM: The aim of the study was to assess whether 2M VWD, defining qualitative
      defects not associated with loss of high molecular weight (HMW) VWF, is often
      misidentified, given highly variable reported frequency ranging from 0 to ~60% of
      all type 2 VWD. METHODS: A comparative evaluation of laboratory ability to
      appropriately identify 2M VWD (n = 4) vs. HMW VWF reduction (n = 4), as sent to
      participants of an international external quality assessment programme. RESULTS:
      Laboratories had considerably greater difficulty identifying type 2M VWD,
      correctly identifying these on average only 29.4% of occasions, with the 70.6%
      error rate representing use of insufficient test panels (41.7%),
      misinterpretation of test results (10.0%) and analytical errors (13.3%). One type
      2M case, giving a median of 49 U dL(-1) VWF:Ag, was more often misidentified as
      type 2A/2B VWD (46.7%) than 2M (34.8%). Another 2M case, giving a median of 189 U
      dL(-1) VWF:Ag, was instead often misidentified as being normal (non-VWD) (36.4%),
      with identifications of type 2A/2B VWD (13.6%) also represented. In comparison,
      errors in identification of HMW VWF reduced samples only averaged 11.5%,
      primarily driven by use of insufficient test panels (6.3%) or misinterpretation
      of results (4.2%) and infrequently analytical errors (1.0%). CONCLUSION: Type 2M
      VWD is more often misidentified (70.6%) than correctly identified as 2M VWD
      (29.4%), and potentially explaining the relative under-reported incidence of 2M
      VWD in the literature.

PMID- 27029719
TI  - [Rare diseases and the CRISPR technology...].

PMID- 27029720
TI  - [SFBC guidelines on critical care testing].
AB  - SFBC working group on critical care testing describes in this paper guideline for
      the management of laboratory medicine examination process in emergency
      conditions. After a summary on French standards and regulations, the critical
      care testing perimeter and definitions of stat levels are presented in different
      contexts. The complete examination process is described. Guidelines are proposed
      for each step, to manage sub-process in a risk management approach. The following
      steps were studied: ordering (by specialties), sampling, transport, reception,
      analysis, validation and release. In summary, we proposed a list of examinations
      allowed to be prescribed in stat conditions with a short list and complementary
      tests as a function of clinical setting. These guidelines need to be adapted in
      clinicobiological contracts. 

PMID- 27029721
TI  - [Diagnosis and practice of virological monitoring of infections by the human
      herpesviruses 6A and 6B].
AB  - The diagnosis of the infection by the human herpesviruses 6A and 6B (HHV-6A, HHV
      6B) is based on a direct and an indirect approaches. Serological methods are
      mainly used to ask primary infection diagnosis and carry out epidemiological
      studies. However, limitations are numerous with, in particular, the existence of
      cross-reactivity with other herpesviruses, and the inability to differentiate the
      two kinds of HHV-6. Initially based on virus isolation in cell culture, direct
      diagnosis evolved with the development of gene amplification methods that provide
      sensitivity and specificity, and allow viral quantitation in many biological
      systems and the identification of present species. Its main current indications
      are the identification of active infection, the identification of the integrated
      form of HHV-6 (iciHHV-6, inherited chromosomally integrated HHV-6) and the
      monitoring of the effectiveness of antiviral treatment. 

PMID- 27029722
TI  - [Monoclonal B-cell lymphocytosis: from literature to laboratory practice].
AB  - Monoclonal B-cell lymphocytosis (MBL) is defined as an asymptomatic condition
      characterized by the presence of less than 5,000 monoclonal B-cells per
      microliter and the absence of clinical signs or symptoms of a B-cell
      lymphoproliferative disorder. Most MBL cases involve B cells presenting an
      identical phenotype to CLL (CLL-like MBL) with a Catovsky-Matutes score of 3 to 5
      and share the same chromosomal abnormalities than CLL. Depending on the absolute
      B cell count, one may distinguish low-count CLL-like MBL (<500 B cells/MUL) which
      have no evidence of progression, no reduction in overall survival, no increase in
      infection risk and do not require any specific follow-up. Patients with clinical
      CLL-like MBL (>500 B cells/MUL) have a 1% to 2% per year risk of progression to
      CLL requiring therapy, a higher risk of infectious complications and mortality
      implicating an annual follow-up by hematologist. MBL may also express other less
      common phenotypes and are named atypical MBL in case of CD5 antigen expression
      (Catovsky-Matutes score: 1-2) and non-CLL-like MBL for CD5 negative cases
      (Catovsky-Matutes score: 0-2). Their poorer prognosis implicates imaging studies,
      bone marrow biopsy and cytogenetic analysis in addition to physical examination
      in order to rule out non-hodgkinien lymphoma, and require a more frequent follow
      up. This review focuses on key concepts in the classification, diagnosis,
      monitoring and biology of MBL in laboratory practice. 

PMID- 27029723
TI  - [New insights in the treatment of chronic lymphocytic leukemia and role of the
      biologist in the monitoring of the treatments].
AB  - Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in
      France. Much progress has been made in recent years in understanding the
      pathophysiology of the disease, the definition of diagnostic criteria (>5 G/L of
      clonal B-lymphocytes), identification of prognostic criteria, including a better
      understanding of fragile patients, high risk patients and even more recently by
      the emergence of new highly effective drugs, doing discuss their place in the
      wide therapeutic panel we have. The treatment of patients with CLL is indicated
      in patients with progressive stage A, stage B or stage C. The new drugs currently
      available include not only the new generation of anti-CD20 monoclonal antibodies,
      type I (ofatumumab) or type II (obinutuzumab), Bcl-2 inhibitors (GDC-0199/ABT
      199) and now the new small molecules available orally, including Bruton tyrosine
      kinase inhibitor (BTK) and phosphor-inositide 3-kinase (PI3K) inhibitor. The role
      of the biologist in monitoring a patient treated for CLL is essential, the latter
      to make the diagnosis of CLL, the search for prognostic factors (Binet stage,
      lymphocyte doubling time, looking for a 17p deletion or TP53 mutations, study of
      mutational profile of heavy chain genes of immunoglobulins IGHV) and biological
      monitoring of the different treatments. We will study in this paper the results
      obtained with these drugs, insisting today more than ever on the need to set up a
      clinical and biological complementarity to allow optimal medical management of
      patients with CLL. The mechanisms of actions are discussed, as well as the
      response criteria we should use to evaluate the effectiveness of these treatments
      in clinical practice. 

PMID- 27029724
TI  - [Current status of urinary iodine analysis and its clinical interest].
AB  - Iodine deficiency especially during pregnancy causes neurological disorders in
      the fetus. Actually, about two billion people are suffering from iodine
      deficiency through the world. The assessment of iodine intake is based on the
      determination of urinary iodine in the target population. Despite the complexity
      of the urinary matrix, a reliable assay must be achieved. After a review of
      pathophysiological interest of urinary iodine, various techniques for its
      measurement and their analytical performance were analyzed in order to select a
      reliable technique and enhance results interpretation. 

PMID- 27029725
TI  - [Validation steps for the detection of L858R mutation in EGFR gene by real time
      quantitative PCR].
AB  - Since January 16(th) 2010, the French legislation requires that the medical
      laboratories must be accredited according to ISO 15189 standards. This concerned
      all the biological medical technics, including molecular biology technics. In
      this work, we described the validation steps by real time quantitative PCR of
      L858R mutation in EGFR gene, frequently detected in non-small lung cancers
      (NSCLC). Epidermal growth factor - tyrosine kinase inhibitors (EGFR-TKIs) are
      authorized in Europe for the treatment of metastatic NSCLC after failure of, at
      least one, prior chemotherapy. Thus, in view of accreditation of this analysis,
      we have used the recommendation of the COFRAC (Comite francais d'accreditation)
      and INCa (Institut national du cancer). Several parameters have been tested, such
      as the primers, the limit of detection, and the sensitivity and specificity of
      the method. In addition, a risk study has been evaluated. Although long and
      fastidious, the method of validation is required to perform analysis in optimal
      conditions to guaranty optimal results for the patients. 

PMID- 27029726
TI  - Molecular identification of Gd A- and Gd B- G6PD deficient variants by ARMS-PCR
      in a Tunisian population.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common
      enzymopathy. More than 200 mutations in the G6PD gene have been described. In
      Tunisia, the A-African and the B-Mediterranean mutations predominate the
      mutational spectrum. The purpose of this study was to apply the amplification
      refractory mutation system (ARMS-PCR) to the identification of Gd A+, Gd A- and
      Gd B- variants in a cohort of deficient individuals and to establish a
      phenotype/genotype association. 90 subjects were screened for enzymatic
      deficiency by spectrophotometric assay. The molecular analyses were performed in
      a group of 50 unrelated patients. Of the 54 altered chromosomes examined, 60% had
      the Gd A- mutation, 18% showed the Gd B- mutation and in 20% of cases, no
      mutations have been identified. The ARMS-PCR showed complete concordance with the
      endonuclease cleavage reference method and agreed perfectly with previous
      Tunisian studies where Gd A- and Gd B- were the most encountered. Also,
      similarities in spectrum mutations with North African and Mediterranean countries
      suggest gene migration from Africa to Europe through Spain. In conclusion, ARMS
      has been introduced in this study for common G6PD alleles identification in
      Tunisia. It gives some advantages compared to the traditional endonuclease
      digestion method since it is more convenient and timesaving and also offers the
      possibility to be applied in mass screening surveys. 

PMID- 27029727
TI  - [The level of evidence for the use of biomarkers in the early detection of
      prostate cancer].
AB  - To systematically review the evidence for the use of PSA and other biomarkers in
      the early detection of prostate cancer, we searched PubMed for clinical trials
      and studies assessing PSA and other biomarkers in the early detection of prostate
      cancer, published between 2000 and May 2013 that included >200 subjects. The
      level of evidence (LOE) for clinical utility was evaluated using the tumor marker
      utility grading system. A total of 84 publications, corresponding to 70 trials
      and studies were selected for inclusion in this review. We attributed a level of
      evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its
      use in mass screening. Emerging biomarkers were assessed in prospective case
      control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5);
      fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to
      determine specificity and sensitivity, but they did not assess the effect on PCa
      mortality. The LoE attributed was III-C. PSA can be used for early prostate
      cancer detection but mass screening is not recommended. Studies on other
      biomarkers suggest that they could be used, individually or in combination, to
      improve the selection of patients with elevated PSA levels for biopsy, but RCTs
      assessing their impact on prostate cancer management and mortality are needed. A
      better use of available tests is possible for men at risk in order to maximize
      the risk-benefit ratio. 

PMID- 27029728
TI  - [The link between trace elements and metabolic syndrome/oxidative stress in
      essential hypertension with or without type 2 diabetes].
AB  - The relationship between trace elements (TE) and essential hypertension (EH) is
      subtle and complex. This relationship is mediated by endothelial dysfunction,
      insulin resistance, oxidative stress (OS) and athero-inflammatory state. The aim
      of this study was to examine the TE impact; particularly selenium (Se), zinc
      (Zn), copper (Cu) and manganese (Mn) as predictive type 2 diabetes biomarkers in
      a hypertensive subject. The study was undertaken on 400 adult patients (40-60
      years), who were divided in 4 groups: hypertensive (H), type 2 diabetes (T2D),
      hypertensive-diabetic (HD) and healthy group. Patients were phenotyped regarding
      their metabolic syndrome profile using the NCEP/ATPIII criteria. Hypertension was
      defined as systolic (SBP) and diastolic (DBP) blood pressure >= 140/90 mmHg,
      respectively. The SBP and DBP measurements by electronic blood pressure using
      Omron 705 CP((r)) type. Insulin resistance was assessed by Homa-IR model.
      Metabolic and inflammatory parameters were determined by Cobas Integra((r)); the
      TE investigated by mass spectrometric atomic absorption; the OS markers evaluated
      by Randox kits. Serum Se concentrations are reduced in all groups, concomitantly
      with a marked depletion GPx activity in the HD group. However, Zn levels were
      decreased than in H and HD groups, but unchanged in T2D group. In contrast, Mn
      levels are increased in all groups; whereas the Cu levels increased only in H and
      HD groups, concomitantly with cytosolic SOD-Cu/Zn and mitochondrial SOD-Mn
      depletion. The Zn/Cu ratio decreases significantly in hypertensive group but not
      in diabetics groups. It appears that Zn/Cu ratio reflects the transition from
      hypertension phase to hypertension associated with T2D. Ultimately, TE plays an
      important role in the hypertension pathophysiology and can be considered as
      predictive T2D biomarkers in hypertensive patients.

PMID- 27029729
TI  - [Analytical performances of real-time PCR by Abbott RealTime CMV with m2000 for
      the detection of cytomegalovirus in urine].
AB  - Congenital cytomegalovirus (CMV) infection is the leading cause of sensoneurinal
      disability due to infectious congenital disease. The diagnosis of congenital CMV
      infection is based on the search of CMV in the urine within the first two weeks
      of life. Viral culture of urine is the gold standard. However, the PCR is highly
      sensitive and faster. It is becoming an alternative choice. The objective of this
      study is the validation of real-time PCR by Abbott RealTime CMV with m2000 for
      the detection of cytomegalovirus in urine. Repeatability, reproducibility,
      detection limit and inter-sample contamination were evaluated. Urine samples from
      patients (n=141) were collected and analyzed simultaneously in culture and PCR in
      order to assess the correlation of these two methods. The sensitivity and
      specificity of PCR were also calculated. The Abbott RealTime CMV PCR in urine is
      an automated and sensitive method (detection limit 200 UI/mL). Fidelity is very
      good (standard deviation of repeatability: 0.08 to 0.15 LogUI/mL and
      reproducibility 0.18 LogUI/mL). We can note a good correlation between culture
      and Abbott RealTime CMV PCR (kappa 96%). When considering rapid culture as
      reference, real-time PCR was highly sensitive (100%) and specific (98.2%). The
      real-time PCR by Abbott RealTime CMV with m2000 is optimal for CMV detection in
      urine. 

PMID- 27029730
TI  - Collaborative Control of Cell Cycle Progression by the RNA Exonuclease Dis3 and
      Ras Is Conserved Across Species.
AB  - Dis3 encodes a conserved RNase that degrades or processes all RNA species via an
      N-terminal PilT N terminus (PIN) domain and C-terminal RNB domain that harbor,
      respectively, endonuclease activity and 3'-5' exonuclease activity. In
      Schizosaccharomyces pombe, dis3 mutations cause chromosome missegregation and
      failure in mitosis, suggesting dis3 promotes cell division. In humans, apparently
      hypomorphic dis3 mutations are found recurrently in multiple myeloma, suggesting
      dis3 opposes cell division. Except for the observation that RNAi-mediated
      depletion of dis3 function drives larval arrest and reduces tissue growth in
      Drosophila, the role of dis3 has not been rigorously explored in higher
      eukaryotic systems. Using the Drosophila system and newly generated dis3 null
      alleles, we find that absence of dis3 activity inhibits cell division. We uncover
      a conserved CDK1 phosphorylation site that when phosphorylated inhibits Dis3's
      exonuclease, but not endonuclease, activity. Leveraging this information, we show
      that Dis3's exonuclease function is required for mitotic cell division: in its
      absence, cells are delayed in mitosis and exhibit aneuploidy and overcondensed
      chromosomes. In contrast, we find that modest reduction of dis3 function enhances
      cell proliferation in the presence of elevated Ras activity, apparently by
      accelerating cells through G2/M even though each insult by itself delays G2/M.
      Additionally, we find that dis3 and ras genetically interact in worms and that
      dis3 can enhance cell proliferation under growth stimulatory conditions in murine
      B cells. Thus, reduction, but not absence, of dis3 activity can enhance cell
      proliferation in higher organisms.

PMID- 27029731
TI  - The Deadbeat Paternal Effect of Uncapped Sperm Telomeres on Cell Cycle
      Progression and Chromosome Behavior in Drosophila melanogaster.
AB  - Telomere-capping complexes (TCCs) protect the ends of linear chromosomes from
      illegitimate repair and end-to-end fusions and are required for genome stability.
      The identity and assembly of TCC components have been extensively studied, but
      whether TCCs require active maintenance in nondividing cells remains an open
      question. Here we show that Drosophila melanogaster requires Deadbeat (Ddbt), a
      sperm nuclear basic protein (SNBP) that is recruited to the telomere by the TCC
      and is required for TCC maintenance during genome-wide chromatin remodeling,
      which transforms spermatids to mature sperm. Ddbt-deficient males produce sperm
      lacking TCCs. Their offspring delay the initiation of anaphase as early as cycle
      1 but progress through the first two cycles. Persistence of uncapped paternal
      chromosomes induces arrest at or around cycle 3. This early arrest can be rescued
      by selective elimination of paternal chromosomes and production of gynogenetic
      haploid or haploid mosaics. Progression past cycle 3 can also occur if embryos
      have reduced levels of the maternally provided checkpoint kinase Chk2. The
      findings provide insights into how telomere integrity affects the regulation of
      the earliest embryonic cell cycles. They also suggest that other SNBPs, including
      those in humans, may have analogous roles and manifest as paternal effects on
      embryo quality.

PMID- 27029732
TI  - Triallelic Population Genomics for Inferring Correlated Fitness Effects of Same
      Site Nonsynonymous Mutations.
AB  - The distribution of mutational effects on fitness is central to evolutionary
      genetics. Typical univariate distributions, however, cannot model the effects of
      multiple mutations at the same site, so we introduce a model in which mutations
      at the same site have correlated fitness effects. To infer the strength of that
      correlation, we developed a diffusion approximation to the triallelic frequency
      spectrum, which we applied to data from Drosophila melanogaster We found a
      moderate positive correlation between the fitness effects of nonsynonymous
      mutations at the same codon, suggesting that both mutation identity and location
      are important for determining fitness effects in proteins. We validated our
      approach by comparing it to biochemical mutational scanning experiments, finding
      strong quantitative agreement, even between different organisms. We also found
      that the correlation of mutational fitness effects was not affected by protein
      solvent exposure or structural disorder. Together, our results suggest that the
      correlation of fitness effects at the same site is a previously overlooked yet
      fundamental property of protein evolution.

PMID- 27029733
TI  - Conserved Genetic Architecture Underlying Individual Recombination Rate Variation
      in a Wild Population of Soay Sheep (Ovis aries).
AB  - Meiotic recombination breaks down linkage disequilibrium (LD) and forms new
      haplotypes, meaning that it is an important driver of diversity in eukaryotic
      genomes. Understanding the causes of variation in recombination rate is important
      in interpreting and predicting evolutionary phenomena and in understanding the
      potential of a population to respond to selection. However, despite attention in
      model systems, there remains little data on how recombination rate varies at the
      individual level in natural populations. Here we used extensive pedigree and high
      density SNP information in a wild population of Soay sheep (Ovis aries) to
      investigate the genetic architecture of individual autosomal recombination rates.
      Individual rates were high relative to other mammal systems and were higher in
      males than in females (autosomal map lengths of 3748 and 2860 cM, respectively).
      The heritability of autosomal recombination rate was low but significant in both
      sexes (h(2) = 0.16 and 0.12 in females and males, respectively). In females,
      46.7% of the heritable variation was explained by a subtelomeric region on
      chromosome 6; a genome-wide association study showed the strongest associations
      at locus RNF212, with further associations observed at a nearby ~374-kb region of
      complete LD containing three additional candidate loci, CPLX1, GAK, and PCGF3 A
      second region on chromosome 7 containing REC8 and RNF212B explained 26.2% of the
      heritable variation in recombination rate in both sexes. Comparative analyses
      with 40 other sheep breeds showed that haplotypes associated with recombination
      rates are both old and globally distributed. Both regions have been implicated in
      rate variation in mice, cattle, and humans, suggesting a common genetic
      architecture of recombination rate variation in mammals.

PMID- 27029734
TI  - Transcript Isoform Variation Associated with Cytosine Modification in Human
      Lymphoblastoid Cell Lines.
AB  - Cytosine modification on DNA is variable among individuals, which could correlate
      with gene expression variation. The effect of cytosine modification on
      interindividual transcript isoform variation (TIV), however, remains unclear. In
      this study, we assessed the extent of cytosine modification-specific TIV in
      lymphoblastoid cell lines (LCLs) derived from unrelated individuals of European
      and African descent. Our study detected cytosine modification-specific TIVs for
      17% of the analyzed genes at a 5% false discovery rate. Forty-five percent of the
      TIV-associated cytosine modifications correlated with the overall gene expression
      levels as well, with the corresponding CpG sites overrepresented in transcript
      initiation sites, transcription factor binding sites, and distinct histone
      modification peaks, suggesting that alternative isoform transcription underlies
      the TIVs. Our analysis also revealed 33% of the TIV-associated cytosine
      modifications that affected specific exons, with the corresponding CpG sites
      overrepresented in exon/intron junctions, splicing branching points, and
      transcript termination sites, implying that the TIVs are attributable to
      alternative splicing or transcription termination. Genetic and epigenetic
      regulation of TIV shared target preference but exerted independent effects on 61%
      of the common exon targets. Cytosine modification-specific TIVs detected from
      LCLs were differentially enriched in those detected from various tissues in The
      Cancer Genome Atlas, indicating their developmental dependency. Genes containing
      cytosine modification-specific TIVs were enriched in pathways of cancers and
      metabolic disorders. Our study demonstrated a prominent effect of cytosine
      modification variation on the transcript isoform spectrum over gross transcript
      abundance and revealed epigenetic contributions to diseases that were mediated
      through cytosine modification-specific TIV.

PMID- 27029735
TI  - Chemotropism and Cell Fusion in Neurospora crassa Relies on the Formation of
      Distinct Protein Complexes by HAM-5 and a Novel Protein HAM-14.
AB  - In filamentous fungi, communication is essential for the formation of an
      interconnected, multinucleate, syncytial network, which is constructed via hyphal
      fusion or fusion of germinated asexual spores (germlings). Anastomosis in
      filamentous fungi is comparable to other somatic cell fusion events resulting in
      syncytia, including myoblast fusion during muscle differentiation, macrophage
      fusion, and fusion of trophoblasts during placental development. In Neurospora
      crassa, fusion of genetically identical germlings is a highly dynamic and
      regulated process that requires components of a MAP kinase signal transduction
      pathway. The kinase pathway components (NRC-1, MEK-2 and MAK-2) and the scaffold
      protein HAM-5 are recruited to hyphae and germling tips undergoing chemotropic
      interactions. The MAK-2/HAM-5 protein complex shows dynamic oscillation to
      hyphae/germling tips during chemotropic interactions, and which is out-of-phase
      to the dynamic localization of SOFT, which is a scaffold protein for components
      of the cell wall integrity MAP kinase pathway. In this study, we functionally
      characterize HAM-5 by generating ham-5 truncation constructs and show that the N
      terminal half of HAM-5 was essential for function. This region is required for
      MAK-2 and MEK-2 interaction and for correct cellular localization of HAM-5 to
      "fusion puncta." The localization of HAM-5 to puncta was not perturbed in 21
      different fusion mutants, nor did these puncta colocalize with components of the
      secretory pathway. We also identified HAM-14 as a novel member of the HAM-5/MAK-2
      pathway by mining MAK-2 phosphoproteomics data. HAM-14 was essential for germling
      fusion, but not for hyphal fusion. Colocalization and coimmunoprecipitation data
      indicate that HAM-14 interacts with MAK-2 and MEK-2 and may be involved in
      recruiting MAK-2 (and MEK-2) to complexes containing HAM-5.

PMID- 27029736
TI  - Timing of Locomotor Recovery from Anoxia Modulated by the white Gene in
      Drosophila.
AB  - Locomotor recovery from anoxia follows the restoration of disordered ion
      distributions and neuronal excitability. The time taken for locomotor recovery
      after 30 sec anoxia (around 10 min) is longer than the time for the propagation
      of action potentials to be restored (<1 min) in Drosophila wild type. We report
      here that the white (w) gene modulates the timing of locomotor recovery. Wild
      type flies displayed fast and consistent recovery of locomotion from anoxia,
      whereas mutants of w showed significantly delayed and more variable recovery.
      Genetic analysis including serial backcrossing revealed a strong association
      between the w locus and the timing of locomotor recovery, and haplo-insufficient
      function of w(+) in promoting fast recovery. The locomotor recovery phenotype was
      independent of classic eye pigmentation, although both are associated with the w
      gene. Introducing up to four copies of mini-white (mw(+)) into w1118 was
      insufficient to promote fast and consistent locomotor recovery. However, flies
      carrying w(+) duplicated to the Y chromosome showed wild-type-like fast locomotor
      recovery. Furthermore, Knockdown of w by RNA interference (RNAi) in neurons but
      not glia delayed locomotor recovery, and specifically, knockdown of w in subsets
      of serotonin neurons was sufficient to delay the locomotor recovery. These data
      reveal an additional role for w in modulating the timing of locomotor recovery
      from anoxia.

PMID- 27029737
TI  - Penetrance of Congenital Heart Disease in a Mouse Model of Down Syndrome Depends
      on a Trisomic Potentiator of a Disomic Modifier.
AB  - Down syndrome (DS) is a significant risk factor for congenital heart disease
      (CHD), increasing the incidence 50 times over the general population. However,
      half of people with DS have a normal heart and thus trisomy 21 is not sufficient
      to cause CHD by itself. Ts65Dn mice are trisomic for orthologs of >100 Hsa21
      genes, and their heart defect frequency is significantly higher than their
      euploid littermates. Introduction of a null allele of Creld1 into Ts65Dn
      increases the penetrance of heart defects significantly. However, this increase
      was not seen when the Creld1 null allele was introduced into Ts1Cje, a mouse that
      is trisomic for about two thirds of the Hsa21 orthologs that are triplicated in
      Ts65Dn. Among the 23 genes present in three copies in Ts65Dn but not Ts1Cje, we
      identified Jam2 as necessary for the increased penetrance of Creld1-mediated
      septal defects in Ts65Dn. Thus, overexpression of the trisomic gene, Jam2, is a
      necessary potentiator of the disomic genetic modifier, Creld1 No direct physical
      interaction between Jam2 and Creld1 was identified by several methods. Regions of
      Hsa21 containing genes that are risk factors of CHD have been identified, but
      Jam2 (and its environs) has not been linked to heart formation previously. The
      complexity of this interaction may be more representative of the clinical
      situation in people than consideration of simple single-gene models.

PMID- 27029738
TI  - It's time to regulate the use of whole body electrical stimulation.

PMID- 27029740
TI  - Measuring Maternal Sensitivity: Cultural Variations in the Measurement of
      Emotional Availability.
AB  - The validity of the Emotional Availability (EA) sensitivity scale was examined in
      Singapore. Participants were mainly from middle-class families of Chinese, Malay,
      Indian, and "Other" ethnic groups. Study 1 involved 30 mother-child dyads
      (children aged 4-6). Scores on EA sensitivity and the Maternal Behavior Q-set
      were highly correlated, suggesting convergent validity. In Study 2 (164 mother
      child dyads), criterion validity was tested by the associations between EA
      sensitivity and children's vocabulary and likability by peers. Unlike findings
      from similar studies conducted in the United States, EA sensitivity was
      negatively correlated with children's likability by female peers, suggesting that
      measures developed in Western contexts may not be fully applicable locally, or
      that the meaning of sensitivity may vary across cultures.

PMID- 27029739
TI  - Blood-based biomarkers of age-associated epigenetic changes in human islets
      associate with insulin secretion and diabetes.
AB  - Aging associates with impaired pancreatic islet function and increased type 2
      diabetes (T2D) risk. Here we examine whether age-related epigenetic changes
      affect human islet function and if blood-based epigenetic biomarkers reflect
      these changes and associate with future T2D. We analyse DNA methylation genome
      wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates
      with increased DNA methylation of 241 sites. These sites cover loci previously
      associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers
      reflect age-related methylation changes in 83 genes identified in human islets
      (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin
      secretion and T2D. DNA methylation correlates with islet expression of multiple
      genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in beta
      cells alter insulin secretion. Together, we demonstrate that blood-based
      epigenetic biomarkers reflect age-related DNA methylation changes in human
      islets, and associate with insulin secretion in vivo and T2D. 

PMID- 27029741
TI  - Hypofractionated ablative radiotherapy for locally advanced pancreatic cancer.
AB  - The role of radiation in locally advanced unresectable pancreatic cancer (LAPC)
      is controversial. Randomized trials evaluating standard doses of chemoradiation
      have not shown a significant benefit from the use of consolidative radiation.
      Results from non-randomized studies of 3-5-fraction stereotactic body
      radiotherapy (SBRT) have been similar to standard chemoradiation, but with less
      toxicity and a shorter treatment time. Doses of SBRT have been reduced to
      subablative levels for the sake of tolerability. The benefit of both options is
      unclear. In contrast, ablative doses can be delivered using an SBRT technique in
      15-28 fractions. The keys to the delivery of ablative doses are computed
      tomography (CT) image guidance and respiratory gating. Higher doses have resulted
      in encouraging long-term survival results. In this review, we present a
      comprehensive solution to achieving ablative doses for selected patients with
      pancreatic tumors by using a combination of classical, modern and novel concepts
      of radiotherapy: fractionation, CT image guidance, respiratory gating,
      intentional dose heterogeneity, and simultaneous integrated protection. 

PMID- 27029744
TI  - Is prostate cancer incidence worldwide linked to artificial light at night
      exposures? Review of earlier findings and analysis of current trends.
AB  - Widespread use of artificial light at night (ALAN) might contribute to the global
      burden of hormone-dependent cancers. Previous attempts to verify this association
      in population-level studies have been sparse. Using GLOBOCAN, US-DMSP, and World
      Bank 2010-2012 databases, we studied the association between ALAN and prostate
      cancer (PC) incidence in 180 countries worldwide, controlling for several country
      level confounders. The PC-ALAN association emerged marginally significant when
      year-2012 PC age-standardized rate data were compared with ALAN levels (t =
      1.886, p < .1); this association was more significant (t > 2.7; p < .01) when
      only 110 countries with well-maintained cancer registries were analyzed. Along
      with other variables, ALAN explains up to 79% of PC ASR variability. PC-ALAN
      association appears to vary regionally, with the greatest deviations in Central
      Africa, Small Island Developing States, Southeast Asia, and Gulf States.

PMID- 27029742
TI  - Quantitative non-invasive cell characterisation and discrimination based on
      multispectral autofluorescence features.
AB  - Automated and unbiased methods of non-invasive cell monitoring able to deal with
      complex biological heterogeneity are fundamentally important for biology and
      medicine. Label-free cell imaging provides information about endogenous
      autofluorescent metabolites, enzymes and cofactors in cells. However extracting
      high content information from autofluorescence imaging has been hitherto
      impossible. Here, we quantitatively characterise cell populations in different
      tissue types, live or fixed, by using novel image processing and a simple
      multispectral upgrade of a wide-field fluorescence microscope. Our optimal
      discrimination approach enables statistical hypothesis testing and intuitive
      visualisations where previously undetectable differences become clearly apparent.
      Label-free classifications are validated by the analysis of Classification
      Determinant (CD) antigen expression. The versatility of our method is illustrated
      by detecting genetic mutations in cancer, non-invasive monitoring of CD90
      expression, label-free tracking of stem cell differentiation, identifying stem
      cell subpopulations with varying functional characteristics, tissue diagnostics
      in diabetes, and assessing the condition of preimplantation embryos. 

PMID- 27029743
TI  - Biotransformation of Daclatasvir In Vitro and in Nonclinical Species: Formation
      of the Main Metabolite by Pyrrolidine delta-Oxidation and Rearrangement.
AB  - Daclatasvir is a first-in-class, potent, and selective inhibitor of the hepatitis
      C virus nonstructural protein 5A replication complex. In support of nonclinical
      studies during discovery and exploratory development, liquid chromatography
      tandem mass spectrometry and nuclear magnetic resonance were used in connection
      with synthetic and radiosynthetic approaches to investigate the biotransformation
      of daclatasvir in vitro and in cynomolgus monkeys, dogs, mice, and rats. The
      results of these studies indicated that disposition of daclatasvir was
      accomplished mainly by the release of unchanged daclatasvir into bile and feces
      and, secondarily, by oxidative metabolism. Cytochrome P450s were the main enzymes
      involved in the metabolism of daclatasvir. Oxidative pathways included delta
      oxidation of the pyrrolidine moiety, resulting in ring opening to an
      aminoaldehyde intermediate followed by an intramolecular reaction between the
      aldehyde and the proximal imidazole nitrogen atom. Despite robust formation of
      the resulting metabolite in multiple systems, rates of covalent binding to
      protein associated with metabolism of daclatasvir were modest (55.2-67.8
      pmol/mg/h) in nicotinamide adenine dinucleotide phosphate (reduced form)
      supplemented liver microsomes (human, monkey, rat), suggesting that
      intramolecular rearrangement was favored over intermolecular binding in the
      formation of this metabolite. This biotransformation profile supported the
      continued development of daclatasvir, which is now marketed for the treatment of
      chronic hepatitis C virus infection.

PMID- 27029746
TI  - Differences in risk for type 1 and type 2 ovarian cancer in a large cancer
      screening trial.
AB  - OBJECTIVE: To investigate the role of previous gynecologic surgery, hormone use,
      and use of non-steroidal anti-inflammatory drugs on the risk of type 1 and type 2
      ovarian cancer. METHODS: We utilized data collected for the Prostate, Lung,
      Colorectal, and Ovarian cancer screening trial. All diagnosed ovarian cancers
      were divided into three groups: type 1, endometrioid, clear cell, mucinous, low
      grade serous, and low grade adenocarcinoma/not otherwise specified (NOS); type 2,
      high grade serous, undifferentiated, carcinosarcoma, and high grade
      adenocarcinoma/NOS; and other: adenocarcinoma with grade or histology not
      specified, borderline tumors, granulosa cell tumors. The odds ratios for type 1,
      type 2, and other ovarian cancers were assessed with regard to historical
      information for specific risk factors. RESULTS: Ibuprofen use was associated with
      a decrease in risk for type 1 ovarian cancer. Tubal ligation and oral
      contraceptive use were associated with a decrease in risk for type 2 ovarian
      cancer. A history of ectopic pregnancy was associated with a decreased risk for
      all ovarian cancers by almost 70%. CONCLUSION: These findings support the
      hypothesis that carcinogenic pathways for type 1 and type 2 ovarian cancer are
      different and distinct. The marked reduction in all ovarian cancer risk noted
      with a history of ectopic pregnancy and salpingectomy implies that the fallopian
      tube plays a key role in carcinogenesis for both type 1 and type 2 ovarian
      cancer.

PMID- 27029745
TI  - Feasibility of laparoscopic cytoreduction in patients with localized recurrent
      epithelial ovarian cancer.
AB  - OBJECTIVE: To assess the feasibility of laparoscopic cytoreduction in patients
      with localized recurrent epithelial ovarian cancer (EOC) by comparing its
      outcomes to those of laparotomy. METHODS: We performed retrospective analysis in
      79 EOC patients who had a localized single recurrent site, as demonstrated by
      computed tomography (CT) scan, magnetic resonance imaging, or positron emission
      tomography/CT scan; had no ascites; were disease-free for 12 or more months
      prior; and who had undergone secondary cytoreduction (laparoscopy in 31 patients,
      laparotomy in 48 patients) at Samsung Medical Center between 2002 and 2013. By
      reviewing the electronic medical records, we investigated the patients' baseline
      characteristics, surgical characteristics, and surgical outcomes. RESULTS: There
      were no statistically significant differences between laparoscopy and laparotomy
      patients in terms of age, body mass index, cancer antigen 125 level, tumor type,
      initial stage, grade, recurrence site, type of procedures used in the secondary
      cytoreduction, adjuvant chemotherapy, and disease-free interval from the previous
      treatment. With regards to surgical outcomes, reduced operating time, shorter
      hospital stay, and less estimated blood loss were achieved in the laparoscopy
      group. Complete debulking was achieved in all cases in the laparoscopy group.
      CONCLUSION: The laparoscopic approach is feasible without compromising morbidity
      and survival in selected groups of patients with recurrent EOC. The laparoscopic
      approach can be a possible treatment option for recurrent EOC.

PMID- 27029747
TI  - Tailored therapy and long-term surveillance of malignant germ cell tumors in the
      female genital system: 10-year experience.
AB  - OBJECTIVE: To explore the appropriate treatment of malignant germ cell tumor
      (MGCT) in the female genital system, and to analyze the factors influencing both
      therapeutic response and survival outcome. METHODS: A cohort of 230-Chinese women
      diagnosed with MGCT of the genital system was retrospectively reviewed and
      prospectively followed. The demographic and pathological features, extent of
      disease and surgery, treatment efficiency, recurrence and survival were analyzed.
      RESULTS: MGCTs from different genital origins shared a similar therapeutic
      strategy and response, except that all eight vaginal cases were infantile yolk
      sac tumors. The patients' cure rate following the initial treatment, 5-year
      overall survival and disease-free survival (DFS) were 85.02%, 95.00%, and 86.00%,
      respectively. Although more extensive excision could enhance the remission rate;
      it did not improve the patients' survival. Instead, the level of the medical
      institution, extent of surgery and disease were independent prognostic factors
      for relapse (p<0.05). Approximately 20% of patients had recurrent or refractory
      disease, more than half of whom were in remission following secondary
      cytoreductive surgery with salvage chemotherapy. CONCLUSION: Fertility-sparing
      surgery with or without standardized PEB/PVB (cisplatin, etoposide/vincristine,
      and bleomycin) chemotherapy is applicable for female MGCTs of different origins.
      Comprehensive staging is not required; nor is excessive debulking suggested.
      Appropriate cytoreduction by surgery and antineoplastic medicine at an
      experienced medical institution can bring about an excellent prognosis for these
      patients.

PMID- 27029748
TI  - Time-lapse imaging of sentinel lymph node using indocyanine green with near
      infrared fluorescence imaging in early endometrial cancer.
AB  - OBJECTIVE: Indocyanine green with near-infrared fluorescence imaging (NIR-ICG) is
      a new tracer modality in the limelight used for lymphatic mapping. The advantage
      of this method is to provide real-time image during surgery. To use ICG for image
      guided lymph node dissection, a surgeon needs to know initial appearing time and
      duration. METHODS: A 52-year-old woman undertook surgery diagnosed with
      endometrial cancer. She had no past medical history and her body mass index was
      25.3 kg/m2. Preoperative magnetic resonance imaging examination revealed 2.7 cm
      sized cancerous mass in the endometrial cavity with superficial myometrial
      invasion without lymph node enlargement. Four mL (1.25 mg/mL) of ICG solution was
      prepared for injection. For each site, 1 mL of solution was injected
      superficially, 2-3 mm into the cervical submucosa and another 1 mL was injected
      deep, 1-2 cm into the stroma of the cervix. We recorded video with 30 degrees  10
      mm scope equipped with a specific lens and light source emitting both visible and
      NIR light (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany). RESULTS: Pelvic lymph
      node was visualized from around 5 minutes. ICG was dispersed into organs after
      hysterectomy (53 minutes after ICG injection), yet we could clearly identify
      sentinel lymph node (SLN). Pathology revealed endometriod adenocarcinoma grade I,
      myometrial invasion with less than half of myometrium and no lymph node
      metastasis. CONCLUSION: Cervical injection of ICG provides good visualization of
      SLN from 5 minutes to over an hour. Our film gives an idea about time management
      to make a plan for surgery and not to miss SNLs.

PMID- 27029749
TI  - Impact of diabetes mellitus on oncological outcomes after radical hysterectomy
      for early stage cervical cancer.
AB  - OBJECTIVE: To evaluate the relationship between type 2 diabetes mellitus (DM) and
      oncological outcomes in early stage cervical cancer patients who underwent
      radical surgical resection. METHODS: Patients with early stage cervical cancer
      diagnosed between 2001 and 2014 were retrospectively enrolled. We assessed the
      outcomes of 402 non-DM and 42 DM patients with cervical cancer. We tested the
      prognostic value of DM via Cox proportional hazard modeling. RESULTS: Patients
      with DM were more likely to be older and overweight. In the DM group, 20 and 22
      patients were and were not taking metformin, respectively. The 5-year recurrence
      free survival (RFS) and 5-year overall survival (OS) rate for the whole study
      population were 88.49% and 96.34%, respectively. In the DM group, there was no
      evidence that metformin affected the RFS (p=0.553) or the OS (p=0.429). In
      multivariate analysis, age (p=0.007), histology (p=0.006), and deep stromal
      invasion (p=0.007) were independent adverse prognostic factors for RFS. There was
      a borderline significant association of increased RFS with DM (p=0.051). However,
      a time-varying-effect Cox model revealed that the DM was associated with a worse
      RFS (hazard ratio, 11.15; 95% CI, 2.00 to 62.08, p=0.022) after 5 years. DM
      (p=0.008), age (p=0.009), and node status (p=0.001) were the only 3 independent
      prognostic factors for OS. CONCLUSION: Early stage cervical cancer patients with
      type 2 DM have a poorer oncological outcome than patients without DM.

PMID- 27029750
TI  - Practice patterns of adjuvant therapy for intermediate/high recurrence risk
      cervical cancer patients in Japan.
AB  - OBJECTIVE: Although radiation therapy (RT) and concurrent chemoradiotherapy
      (CCRT) are the global standards for adjuvant therapy treatment in cervical
      cancer, many Japanese institutions choose chemotherapy (CT) because of the low
      frequency of irreversible adverse events. In this study, we aimed to clarify the
      trends of adjuvant therapy for intermediate/high-risk cervical cancer after
      radical surgery in Japan. METHODS: A questionnaire survey was conducted by the
      Japanese Gynecologic Oncology Group to 186 authorized institutions active in the
      treatment of gynecologic cancer. RESULTS: Responses were obtained from 129
      facilities. Adjuvant RT/CCRT and intensity-modulated RT were performed in 98
      (76%) and 23 (18%) institutions, respectively. On the other hand, CT was chosen
      as an alternative in 93 institutions (72%). The most common regimen of CT, which
      was used in 66 institutions (51%), was a combination of cisplatin/carboplatin
      with paclitaxel. CT was considered an appropriate alternative option to RT/CCRT
      in patients with risk factors such as bulky tumors, lymph node metastasis,
      lymphovascular invasion, parametrial invasion, and stromal invasion. The risk of
      severe adverse events was considered to be lower for CT than for RT/CCRT in 109
      institutions (84%). CONCLUSION: This survey revealed a variety of policies
      regarding adjuvant therapy among institutions. A clinical study to assess the
      efficacy or non-inferiority of adjuvant CT is warranted.

PMID- 27029751
TI  - Preventive vaccination against cervical cancer: Korean Society of Gynecologic
      Oncology Guideline.
AB  - After human papillomavirus (HPV) vaccine guidelines published by Korean Society
      of Gynecologic Oncology (KSGO) in 2011, new studies have been published, leading
      to additional data regarding efficacy, safety, number of vaccination rounds, and
      ideal age of vaccine administration. We searched and reviewed the literatures
      focused on the efficacy of 2-dose schedule vaccination, the efficacy of 3-dose
      schedule vaccination in middle-aged women, the ideal age of 3-dose schedule
      vaccination, the safety of HPV preventive vaccine, and the ability of cross
      protection of each HPV preventive vaccine. The KSGO has revised the previous
      guideline based on the results of the above studies. 

PMID- 27029752
TI  - Clear cell carcinoma of the ovary: molecular insights and future therapeutic
      perspectives.
AB  - Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to
      chemotherapeutic agents and to be associated with a worse prognosis than the more
      common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the
      survival of patients with ovarian CCC, the deeper understanding of the mechanism
      of CCC carcinogenesis as well as the efforts to develop novel treatment
      strategies in the setting of both front-line treatment and salvage treatment for
      recurrent disease are needed. In this presentation, we first summarize the
      mechanism responsible for carcinogenesis. Then, we highlight the promising
      therapeutic targets in ovarian CCC and provide information on the novel agents
      which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti
      cancer agents that can be best combined with targeted agents in the treatment of
      ovarian CCC. 

PMID- 27029753
TI  - Single-port laparoscopic transperitoneal infrarenal para-aortic lymphadenectomy
      as part of staging operation for early ovarian cancer and high grade endometrial
      cancer.
AB  - OBJECTIVE: The aim of this paper was to demonstrate the techiniqes of single-port
      laparoscopic transperitoneal infrarenal paraaortic lymphadenectomy as part of
      surgical staging procedure in case of early ovarian cancer and high grade
      endometrial cancer. METHODS: After left upper traction of rectosigmoid, a
      peritoneal incision was made caudad to inferior mesenteric artery. Rectosigmoid
      was mobilized, and then the avascular space of the lateral rectal portion was
      found by using upward traction of rectosigmoid mesentery. Inframesenteric nodes
      were removed without injury to the ureter and the left common iliac nodes were
      easily removed due to the upward traction of the rectosigmoid. The superior
      hypogastric plexus was found overlying the aorta and sacral promontory, and
      presacral nodes were removed at subaortic area. Peritoneal traction suture to
      right abdomen was needed for right para-aortic lymphadenectomy. After right lower
      para-aortic node dissection, operator was situated between the patient's legs.
      After upper traction of the small bowel, left upper para-aortic nodes were
      removed. To prevent chylous ascites, we used hemolock or Ligasure application
      (ValleyLab Inc.) to upper part of infrarenal and aortocaval nodes. RESULTS:
      Single-port laparoscopic transperitoneal infrarenal para-aortic lymphadenectomy
      was performed without serious perioperative complications. CONCLUSION: Even
      though the technique of single-port surgery is still a difficult operation, the
      quality of single-port laparoscopic transperitoneal infrarenal para-aortic node
      dissection is excellent, especially mean number of para-aortic nodes. In cases of
      staging procedures for ovary and endometrial cancer, single-port transperitoneal
      para-aortic lymphadenectomy is acceptable as an oncologic procedure.

PMID- 27029754
TI  - Embryos need a cozy house.

PMID- 27029755
TI  - Ovary is necessary to the health of uterus.

PMID- 27029756
TI  - [Atrial fibrillation ablation during mitral valve surgery].

PMID- 27029757
TI  - [Prevention of sudden cardiac death in the 2015 ESC guidelines].

PMID- 27029758
TI  - [Idiopathic massive myocardial calcification: a rare cause of heart failure].
AB  - Massive myocardial calcification is a very rare finding usually associated with
      previous myocardial infarction, ventricular aneurysms, myocarditis,
      endomyocardial fibrosis, tuberculosis and systemic metabolic disease such as
      sarcoidosis and primary hyperoxaluria. Rarely, it can be associated with
      idiopathic mitral annular calcification or rheumatic heart disease. We report an
      unusual case of massive myocardial calcification without other predisposing
      factors and with documented disease progression. 

PMID- 27029759
TI  - [The Pacemaker and Implantable Cardioverter-Defibrillator Registry of the Italian
      Association of Arrhythmology and Cardiac Pacing--Annual report 2014].
AB  - BACKGROUND: The pacemaker (PM) and implantable cardioverter-defibrillator (ICD)
      Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)
      monitors the main epidemiological data in real-world practice. The survey for the
      2014 activity collects information about demographics, clinical characteristics,
      main indications for PM/ICD therapy and device types from the Italian
      collaborating centers. METHODS: The Registry collects prospectively national PM
      and ICD implantation activity on the basis of European cards. RESULTS: PM
      Registry: data about 24 680 PM implantations were collected (19 480 first implant
      and 5200 replacements). The number of collaborating centers was 208. Median age
      of treated patients was 81 years (75 quartile I; 86 quartile III). ECG
      indications included atrioventricular conduction disorders in 45.3% of first PM
      implants, sick sinus syndrome in 23.1%, atrial fibrillation plus bradycardia in
      11.7%, other in 19.9%. Among atrioventricular conduction defects, third-degree
      atrioventricular block was the most common type (22.7% of first implants). Use of
      single-chamber PMs was reported in 26.9% of first implants, of dual-chamber PMs
      in 63.6%, of PMs with cardiac resynchronization therapy (CRT) in 1.7%, and of
      single lead atrial-synchronized ventricular stimulation (VDD/R PMs) in 7.8%. ICD
      Registry: data about 17 116 ICD implantations were collected (11 274 first
      implants and 5842 replacements). The number of collaborating centers was 424.
      Median age of treated patients was 71 years (62 quartile I; 77 quartile III).
      Primary prevention indication was reported in 72.3% of first implants, secondary
      prevention in 27.7% (cardiac arrest in 10.1%). A single-chamber ICD was used in
      32.2% of first implants, dual-chamber in 37.1% and biventricular in 30.7%.
      CONCLUSIONS: The PM and ICD Registry appears fundamental for monitoring PM and
      ICD utilization on a large national scale with rigorous examination of
      demographics and clinical indications. The PM Registry showed stable
      electrocardiographic and symptom indications, with an important prevalence of
      dual-chamber pacing. The use of CRT-PM regards a very limited number of patients.
      The ICD Registry documented a large use of prophylactic and biventricular ICD,
      reflecting a favorable adherence to trials and guidelines in clinical practice.

PMID- 27029760
TI  - [2015 ESC Guidelines for the management of patients with ventricular arrhythmias
      and the prevention of sudden cardiac Death. The Task Force for the Management of
      Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
      of the European Society of Cardiology].

PMID- 27029763
TI  - Loading the FeNiOOH cocatalyst on Pt-modified hematite nanostructures for
      efficient solar water oxidation.
AB  - A FeNiOOH-decorated hematite photoanode has been prepared using a facile
      electrodeposition method, with a significant cathodic shift of the onset
      potential (up to 190 mV) compared to the pristine sample. Synchrotron radiation
      based techniques have been used to identify the composition of the catalyst
      indicating the presence of FeOOH and NiOOH (FeNiOOH). The enhanced performance
      can be attributed to the better oxidation evolution reaction kinetics with the
      FeNiOOH cocatalyst. The FeNiOOH-decorated hematite is very stable for a long
      time. Moreover, the cocatalyst can be well coupled to the Pt-modified hematite
      photoanode achieving a high photocurrent of 2.21 mA cm(-2) at 1.23 V vs. RHE. The
      good catalytic properties and the facile preparation method suggest that the
      decoration of FeNiOOH is a favorable strategy to improve the performance of
      hematite.

PMID- 27029762
TI  - Radial glia inhibit peripheral glial infiltration into the spinal cord at motor
      exit point transition zones.
AB  - In the mature vertebrate nervous system, central and peripheral nervous system
      (CNS and PNS, respectively) GLIA myelinate distinct motor axon domains at the
      motor exit point transition zone (MEP TZ). How these cells preferentially
      associate with and myelinate discrete, non-overlapping CNS versus PNS axonal
      segments, is unknown. Using in vivo imaging and genetic cell ablation in
      zebrafish, we demonstrate that radial glia restrict migration of PNS glia into
      the spinal cord during development. Prior to development of radial glial endfeet,
      peripheral cells freely migrate back and forth across the MEP TZ. However, upon
      maturation, peripherally located cells never enter the CNS. When we ablate radial
      glia, peripheral glia ectopically migrate into the spinal cord during
      developmental stages when they would normally be restricted. These findings
      demonstrate that radial glia contribute to both CNS and PNS development and
      control the unidirectional movement of glial cell types across the MEP TZ early
      in development. GLIA 2016. GLIA 2016;64:1138-1153.

PMID- 27029764
TI  - Metabolic network architecture and carbon source determine metabolite production
      costs.
AB  - Metabolism is essential to organismal life, because it provides energy and
      building block metabolites. Even though it is known that the biosynthesis of
      metabolites consumes a significant proportion of the resources available to a
      cell, the factors that determine their production costs remain less well
      understood. In this context, it is especially unclear how the nutritional
      environment affects the costs of metabolite production. Here, we use the amino
      acid metabolism of Escherichia coli as a model to show that the point at which a
      carbon source enters central metabolic pathways is a major determinant of
      individual metabolite production costs. Growth rates of auxotrophic genotypes,
      which in the presence of the required amino acid save biosynthetic costs, were
      compared to the growth rates that prototrophic cells achieved under the same
      conditions. The experimental results showed a strong concordance with
      computationally estimated biosynthetic costs, which allowed us, for the first
      time, to systematically quantify carbon source-dependent metabolite production
      costs. Thus, we demonstrate that the nutritional environment in combination with
      network architecture is an important but hitherto underestimated factor
      influencing biosynthetic costs and thus microbial growth. Our observations are
      highly relevant for the optimization of biotechnological processes as well as for
      understanding the ecology of microorganisms in their natural environments.

PMID- 27029765
TI  - Stylistic analysis of headlines in science journalism: A case study of New
      Scientist.
AB  - This article explores science journalism in the context of the media competition
      for readers' attention. It offers a qualitative stylistic perspective on how
      popular journalism colonizes science communication. It examines a sample of 400
      headlines collected over the period of 15 months from the ranking of five 'most
      read' articles on the website of the international magazine New Scientist.
      Dominant lexical properties of the sample are first identified through frequency
      and keyness survey and then analysed qualitatively from the perspective of the
      stylistic projection of newsworthiness. The analysis illustrates various degrees
      of stylistic 'hybridity' in online popularization of scientific research.
      Stylistic patterns that celebrate, domesticate or personalize science coverage
      (characteristic of popular journalism) are intertwined with devices that
      foreground tentativeness, precision and informativeness (characteristic of
      science communication). The article reflects on the implications of including
      various proportions of academic and popular styles in science journalism.

PMID- 27029766
TI  - The first bite: Imaginaries, promotional publics and the laboratory grown burger.
AB  - In this article, we analyse a 2013 press conference hosting the world's first
      tasting of a laboratory grown hamburger. We explore this as a media event: an
      exceptional performative moment in which common meanings are mobilised and a
      connection to a shared centre of reality is offered. We develop our own
      theoretical contribution - the promotional public - to characterise the
      affirmative and partial patchwork of carefully selected actors invoked during the
      burger tasting. Our account draws on three areas of analysis: interview data with
      the scientists who developed the burger, media analysis of the streamed press
      conference itself and media analysis of social media during and following the
      event. We argue that the call to witness an experiment is a form of promotion and
      that such promotional material also offers an address that invokes a public with
      its attendant tensions.

PMID- 27029767
TI  - Reproducibility: It Is Just Good Science.

PMID- 27029770
TI  - Resonant surface plasmon-exciton interaction in hybrid MoSe2@Au nanostructures.
AB  - In this work we investigate the interaction between plasmonic and excitonic
      resonances in hybrid MoSe2@Au nanostructures. The latter were fabricated by
      combining chemical vapor deposition of MoSe2 atomic layers, Au disk processing by
      nanosphere lithography and a soft lift-off/transfer technique. The samples were
      characterized by scanning electron and atomic force microscopy. Their optical
      properties were investigated experimentally using optical absorption, Raman
      scattering and photoluminescence spectroscopy. The work is focused on a resonant
      situation where the surface plasmon resonance is tuned to the excitonic
      transition. In that case, the near-field interaction between the surface plasmons
      and the confined excitons leads to interference between the plasmonic and
      excitonic resonances that manifests in the optical spectra as a transparency dip.
      The plasmonic-excitonic interaction regime is determined using quantitative
      analysis of the optical extinction spectra based on an analytical model supported
      by numerical simulations. We found that the plasmonic-excitonic resonances do
      interfere thus leading to a typical Fano lineshape of the optical extinction. The
      near-field nature of the plasmonic-excitonic interaction is pointed out
      experimentally from the dependence of the optical absorption on the number of
      monolayer stacks on the Au nanodisks. The results presented in this work
      contribute to the development of new concepts in the field of hybrid plasmonics. 

PMID- 27029768
TI  - Comparison of Predictive Immunohistochemical Marker Expression of Primary Breast
      Cancer and Paired Distant Metastasis using Surgical Material: A Practice-Based
      Study.
AB  - Parallel studies of primary breast carcinomas and corresponding distant
      metastases samples reveal considerable differences. Our aim was to highlight this
      issue from another perspective and provide further data based on 98 patient
      samples: 69 primary breast carcinoma and 85 distant metastases from bone, central
      nervous system (CNS) and lung (56 paired). Two independent series of
      immunohistochemical reactions with different antibodies for estrogen receptor
      (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2
      (Her2), along with HER2 fluroscence in situ hybridization (FISH) were performed
      on tissue microarrays to classify breast carcinoma and distant metastases samples
      into Luminal A, Luminal B-proliferating, Luminal B-HER2+, HER2+ and triple
      negative (TNBC) surrogate breast cancer groups. Correlation and agreement between
      the two assessments of ER and PgR were fair-to-moderate, and almost perfect for
      HER2 and Ki67. There was 40% discordance concerning immunophenotype between
      breast carcinomas and distant metastases. Most common metastatic site of ER+
      breast carcinoma was the skeletal system (59.2%), whereas that of TNBCs was the
      CNS (58.8%) and lungs (23.5%). Distant metastases in bones were mostly luminal
      (54.3%), in the CNS, Luminal B (53.2%), and in the lung, TNBC (37.5%). The change
      of drugable properties of primary breast cancers in the respective bone and CNS
      metastases suggests that characterization of the metastasis is necessary for
      appropriate treatment planning.

PMID- 27029769
TI  - Argonaute2 Protein in Rat Spermatogenic Cells Is Localized to Nuage Structures
      and LAMP2-Positive Vesicles Surrounding Chromatoid Bodies.
AB  - Localization of Argonaute2 (AGO2) protein--an essential component for the
      processing of small interfering RNA (siRNA)-directed RNA interference (RNAi) in
      RNA-induced silencing complex (RISC) in nuage of rat spermatogenic cells--was
      evaluated by immunofluorescence microscopy (IFM) and immunoelectron microscopy
      (IEM). AGO2 was shown, for the first time, to be localized to four previously
      classified types of nuage: irregularly shaped perinuclear granules (ISPGs),
      intermitochondrial cement (IMC), satellite bodies (SBs), and chromatoid bodies
      (CBs). Dual IEM staining for AGO2/Maelstrom (MAEL) protein or AGO2/MIWI protein
      demonstrated that AGO2 is colocalized with MAEL or MIWI proteins in these types
      of nuage. Dual IFM and IEM staining of AGO2/lysosomal-associated membrane protein
      2 (LAMP2) showed that CB in round spermatids are in contact with and surrounded
      by LAMP2-positive vesicles, whereas nuage in pachytene spermatocytes are not.
      Taken together, our findings indicate that: (i) AGO2 in pachytene spermatocytes
      functions in ISPGs, IMC, and SBs; (ii) AGO2 in round spermatids functions in CBs,
      and that CBs are associated with lysosomal compartments.

PMID- 27029771
TI  - Association of socioeconomic status change between infancy and adolescence, and
      blood pressure, in South African young adults: Birth to Twenty Cohort.
AB  - OBJECTIVE: Social epidemiology models suggest that socioeconomic status (SES)
      mobility across the life course affects blood pressure. The aim of this study was
      to investigate the association between SES change between infancy and
      adolescence, and blood pressure, in young adults, and the impact of early growth
      on this relationship. SETTING: Data for this study were obtained from a 'Birth to
      Twenty' cohort in Soweto, Johannesburg, in South Africa. PARTICIPANTS: The study
      included 838 Black participants aged 18 years who had household SES measures in
      infancy and at adolescence, anthropometry at 0, 2, 4 and 18 years of age and
      blood pressure at the age of 18 years. METHODS: We computed SES change using
      asset-based household SES in infancy and during adolescence as an exposure
      variable, and blood pressure and hypertension status as outcomes. Multivariate
      linear and logistic regressions were used to investigate the associations between
      SES change from infancy to adolescence, and age, height and sex-specific blood
      pressure and hypertension prevalence after adjusting for confounders. RESULTS:
      Compared to a persistent low SES, an upward SES change from low to high SES
      tertile between infancy and adolescence was significantly associated with lower
      systolic blood pressure (SBP) at the age of 18 years (beta=-4.85; 95% CI -8.22 to
      -1.48; p<0.01; r(2)=0.1804) after adjusting for SES in infancy, small-for
      gestational-age (SGA) and weight gain. Associations between SES change and SBP
      were partly explained by weight gain between birth and the age of 18 years. There
      was no association between SES mobility and diastolic blood pressure, mean
      arterial pressure or hypertension status. CONCLUSIONS: Our study confirms that
      upward SES change has a protective effect on SBP by the time participants reach
      young adulthood. Socioeconomic policies and interventions that address inequality
      may have the potential to reduce cardiovascular disease burden related to BP in
      later life.

PMID- 27029772
TI  - Effects of prehospital hypothermia on transfusion requirements and outcomes: a
      retrospective observatory trial.
AB  - OBJECTIVES: Prehospital hypothermia is defined as a core temperature <36.0 
      degrees C and has been shown to be an independent risk factor for early death in
      patients with trauma. In a retrospective study, a possible correlation between
      the body temperature at the time of admission to the emergency room and
      subsequent in-hospital transfusion requirements and the in-hospital mortality
      rate was explored. SETTING: This is a retrospective single-centre study at a
      primary care hospital in Germany. PARTICIPANTS: 15,895 patients were included in
      this study. Patients were classified by admission temperature and transfusion
      rate. Excluded were ambulant patients and patients with missing data. PRIMARY AND
      SECONDARY OUTCOME MEASURES: The primary outcome values were length of stay (LOS)
      in days, in-hospital mortality, the transferred amount of packed red blood cells
      (PRBCs), and admission to an intensive care unit. Secondary influencing variables
      were the patient's age and the Glasgow Coma Scale. RESULTS: In 22.85% of the
      patients, hypothermia was documented. Hypothermic patients died earlier in the
      course of their hospital stay than non-hypothermic patients (p<0.001). The
      administration of 1-3 PRBC increased the LOS significantly (p<0.001) and
      transfused patients had an increased risk of death (p<0.001). Prehospital
      hypothermia could be an independent risk factor for mortality (adjusted OR 8.521;
      p=0.001) and increases the relative risk for transfusion by factor 2.0 (OR 2.007;
      p=0.002). CONCLUSIONS: Low body temperature at hospital admission is associated
      with a higher risk of transfusion and death. Hence, a greater awareness of
      prehospital temperature management should be established.

PMID- 27029773
TI  - Applying appropriate-use criteria to cardiac revascularisation in India.
AB  - OBJECTIVES: The high prevalence of coronary heart disease and dramatic growth of
      cardiac interventions in India motivate an evaluation of the appropriateness of
      coronary revascularisation procedures in India. Although, appropriate-use
      criteria (AUC) have been used to analyse the appropriateness of cardiovascular
      care in the USA, they are yet to be applied to care in India. In our study, we
      apply AUC to cardiac care in Karnataka, India, compare our results to
      international applications of AUC, and suggest ways to improve the
      appropriateness of care in India. SETTING: Data were collected from the Vajpayee
      Arogyashree Scheme, a government-sponsored health insurance scheme in Karnataka,
      India. These data were collected as part of the preauthorisation process for
      cardiac procedures. PARTICIPANTS: The final data included a random sample of 600
      patients from 28 hospitals in Karnataka, who obtained coronary artery bypass
      grafting or percutaneous coronary intervention between 1 October 2014 and 31
      December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: We obtained our primary
      baseline results using a random imputation simulation to fill in missing data.
      Our secondary outcome measure was a best case-worst case scenario where missing
      data were filled to give the lowest or highest number of appropriate cases.
      RESULTS: Of the cases, 86.7% (CI 0.837% to 0.892%) were deemed appropriate, 3.65%
      (CI 0.023% to 0.055%) were inappropriate and 9.63% (CI 0.074% to 0.123%) were
      uncertain. CONCLUSIONS: The vast majority of cardiac revascularisation procedures
      performed on beneficiaries of a government-sponsored insurance programme in India
      were found to be appropriate. These results meet or exceed levels of appropriate
      use of cardiac care in the USA.

PMID- 27029774
TI  - Time trends in statin utilisation and coronary mortality in Western European
      countries.
AB  - OBJECTIVES: To determine whether there is a relation between statin utilisation
      and coronary heart disease (CHD) mortality in populations with different levels
      of coronary risk, and whether the relation changes over time. DESIGN: Ecological
      study using national databases of dispensed medicines and mortality rates.
      SETTING: Western European countries with similar public health systems. MAIN
      OUTCOME MEASURES: Population CHD mortality rates (rate/100,000) as a proxy for
      population coronary risk level, and statin utilisation expressed as Defined Daily
      Dose per one Thousand Inhabitants per Day (DDD/TID), in each country, for each
      year between 2000 and 2012. Spearman's correlation coefficients between CHD
      mortality and statin utilisation were calculated. Linear regression analysis was
      used to assess the relation between changes in CHD mortality and statin
      utilisation over the years. RESULTS: 12 countries were included in the study.
      There was a wide range of CHD mortality reduction between the years 2000 and 2012
      (from 25.9% in Italy to 57.9% in Denmark) and statin utilisation increase (from
      121% in Belgium to 1263% in Denmark). No statistically significant relations were
      found between CHD mortality rates and statin utilisation, nor between changes in
      CHD and changes in statin utilisation in the countries over the years 2000 and
      2012. CONCLUSIONS: Among the Western European countries studied, the large
      increase in statin utilisation between 2000 and 2012 was not associated with CHD
      mortality, nor with its rate of change over the years. Factors different from the
      individual coronary risk, such as population ageing, health authority programmes,
      guidelines, media attention and pharmaceutical industry marketing, may have
      influenced the large increase in statin utilisation. These need to be re-examined
      with a greater emphasis on prevention strategies.

PMID- 27029776
TI  - Short sleep duration and risk of nonalcoholic fatty liver disease: A systematic
      review and meta-analysis.
AB  - BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is one of the most
      common causes of chronic liver disease worldwide. Several studies have suggested
      that short sleep duration could be a risk factor for NAFLD. However, results of
      those reports are inconsistent. This meta-analysis was conducted with an attempt
      to summarize all available data. METHODS: A comprehensive literature review was
      performed using MEDLINE and EMBASE database. Studies that reported relative
      risks, odd ratios or hazard ratios comparing the risk of NAFLD among participants
      who had short sleep duration versus those with longer sleep duration were
      included. Pooled risk ratios and 95% confidence interval were calculated using a
      random-effect, generic inverse variance method. RESULTS: Six studies met the
      eligibility criteria and were included in the meta-analysis. The risk of NAFLD in
      participants who had short sleep duration was significantly higher than
      participants with longer sleep duration with pooled risk ratios of 1.19 (95%
      confidence interval, 1.04-1.36, I2  = 0%). CONCLUSIONS: Our study demonstrated a
      small but significantly increased risk of NAFLD among participants who had short
      sleep duration.

PMID- 27029775
TI  - Optimising text messaging to improve adherence to web-based smoking cessation
      treatment: a randomised control trial protocol.
AB  - INTRODUCTION: Millions of smokers use the Internet for smoking cessation
      assistance each year; however, most smokers engage minimally with even the best
      designed websites. The ubiquity of mobile devices and their effectiveness in
      promoting adherence in other areas of health behaviour change make them a
      promising tool to address adherence in Internet smoking cessation interventions.
      Text messaging is used by most adults, and messages can proactively encourage use
      of a web-based intervention. Text messaging can also be integrated with an
      Internet intervention to facilitate the use of core Internet intervention
      components. METHODS AND ANALYSIS: We identified four aspects of a text message
      intervention that may enhance its effectiveness in promoting adherence to a web
      based smoking cessation programme: personalisation, integration, dynamic
      tailoring and message intensity. Phase I will use a two-level full factorial
      design to test the impact of these four experimental features on adherence to a
      web-based intervention. The primary outcome is a composite metric of adherence
      that incorporates general utilisation metrics (eg, logins, page views) and
      specific feature utilisation shown to predict abstinence. Participants will be
      N=860 adult smokers who register on an established Internet cessation programme
      and enrol in its text message programme. Phase II will be a two-arm randomised
      trial to compare the efficacy of the web-based cessation programme alone and in
      conjunction with the optimised text messaging intervention on 30-day point
      prevalence abstinence at 9 months. Phase II participants will be N=600 adult
      smokers who register to use an established Internet cessation programme and enrol
      in text messaging. Secondary analyses will explore whether adherence mediates the
      effect of treatment condition on outcome. ETHICS AND DISSEMINATION: This protocol
      was approved by Chesapeake IRB. We will disseminate study results through peer
      reviewed manuscripts and conference presentations related to the methods and
      design, outcomes and exploratory analyses. TRIAL REGISTRATION NUMBER:
      NCT02585206.

PMID- 27029777
TI  - Serotype-Specific Cell-Mediated Immunity Associated With Clearance of Homotypic
      Group B Streptococcus Rectovaginal Colonization in Pregnant Women.
AB  - We investigated the association between group B Streptococcus (GBS) serotype
      specific capsular polysaccharide cellular immunity, measured with enzyme-linked
      immunospot (ELISPOT) interferon gamma release assay at 20 weeks gestation in
      pregnant women, and its effect on rectovaginal serotype-specific GBS colonization
      up to 37 weeks gestation. Among women colonized by serotype III at enrollment,
      interferon gamma ELISPOT positivity was more common in those in whom colonization
      was cleared (44.4%) than in those in whom colonization persisted (7.4%; P =
      .008), with a similar trend observed for serotype Ia. Presence of serotype
      specific capsular polysaccharide cell-mediated immunity contributes to the
      clearance of GBS rectovaginal colonization.

PMID- 27029779
TI  - Sensitive detection of intracellular RNA of human telomerase by using graphene
      oxide as a carrier to deliver the assembly element of hybridization chain
      reaction.
AB  - Since the level of human telomerase RNA (hTR) in tumor cells is higher than that
      in normal somatic cells, the quantitative assay of hTR is of significant
      importance in tumor diagnosis. Herein, graphene oxide (GO) was simultaneously
      exploited as a fluorescence quencher and a carrier of nucleic acid to
      successfully deliver two hairpin DNA probes of hybridization chain reaction (HCR)
      into the cancer cell for detecting telomerase RNA based on DNA nanoassembly of
      HCR. The sticky end of HCR probes could tightly absorb on the surface of GO,
      resulting in fluorescence quenching of the dye which was tagged at the sticky end
      of two hairpin probes. When faced with hTR, the fluorescence of DNA probes is
      subsequently recovered because hTR could trigger HCR to autonomous assembly of a
      DNA polymer which released from the GO and led to fluorescence recovery. Taking
      advantage of nucleic acid nanoassembly of HCR, this intracellular HCR strategy
      creates enormous signal amplification, and enables ultra-sensitive fluorescence
      imaging of hTR expression. By monitoring fluorescence change, human telomerase
      RNA could be specifically studied and this method can also be used for detecting
      single-base mutation. The GO-aided HCR strategy allowed us to sensitively detect
      hTR in a living cell, which holds great potential for analyzing other low
      abundance biomolecules in living cells via HCR.

PMID- 27029778
TI  - Low Risk of Proximal Tubular Dysfunction Associated With Emtricitabine-Tenofovir
      Disoproxil Fumarate Preexposure Prophylaxis in Men and Women.
AB  - OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is associated with proximal
      tubular dysfunction (tubulopathy) when used in the treatment of human
      immunodeficiency virus (HIV) infection. We evaluated whether TDF causes
      tubulopathy when used as HIV preexposure prophylaxis (PrEP) and whether
      tubulopathy predicts clinically relevant decline (>=25%) in the estimated
      glomerular filtration rate (eGFR). METHODS: A subgroup analysis of the Partners
      PrEP Study, a randomized, placebo-controlled trial of daily oral TDF, alone or
      with emtricitabine (FTC), in HIV-uninfected African men and women
      (Clinicaltrials.gov NCT00557245). Tubulopathy was assessed in concurrently
      obtained urine and serum samples at the 24-month or last on-treatment visit,
      predefined as >=2 of the following: tubular proteinuria, euglycemic glycosuria,
      increased urinary phosphate, and uric acid excretion. RESULTS: Of 1549 persons
      studied (776 receiving FTC-TDF, 773 receiving placebo), 64% were male, and the
      median age was 37 years. Over a median 24 months of study-drug exposure, the
      frequency of tubulopathy was 1.7% for FTC-TDF versus 1.3% for placebo (odds
      ratio, 1.30; 95% confidence interval, .52-3.33; P = .68); Tubulopathy occurred in
      2 of 52 persons (3.8%) with versus 3 of 208 (1.4%) without >=25% eGFR decline
      (adjusted odds ratio, 1.39; .10-14.0; P > .99). CONCLUSIONS: Daily oral FTC-TDF
      PrEP was not significantly associated with tubulopathy over the course of 24
      months, nor did tubulopathy predict clinically relevant eGFR decline.

PMID- 27029780
TI  - Phase selective synthesis of quantum cutting nanophosphors and the observation of
      a spontaneous room temperature phase transition.
AB  - Oxygen-free Eu(3+)-doped NaGdF4 nanocrystals with high quantum cutting efficiency
      are accessible at low temperatures (room temperature to 80  degrees C) using task
      specific ionic liquids (ILs) as structure directing agents and only water as
      solvent. Selective tuning of the shape, morphology and, most importantly, the
      crystal phase of the host lattice is achieved by changing the alkyl side length,
      the H-bonding capabilities and the concentration of 1-alkyl-3-methylimidazolium
      bromide ILs, [C(n)mim]Br. When using [C2mim]Br, hexagonal NaGdF4 nanoparticles
      are obtained. In the case of methylimidazolium bromides with longer pendant alkyl
      chains such as butyl (C4), octyl (C8) or decyl (C10), extremely small
      nanoparticles of the cubic polymorph form, which then convert even at room
      temperature (RT) to the thermodynamically favored hexagonal modification. To the
      best of our knowledge, this kind of spontaneous phase transition is not yet
      reported. The hexagonal nanomaterial shows a substantial quantum cutting
      efficiency (154%) whilst in the cubic material, the effect is negligible (107%).
      The easy yet highly phase selective green synthesis of the materials promises
      large scale industrial application in environmentally benign energy efficient
      lighting.

PMID- 27029781
TI  - Visual adaptation dominates bimodal visual-motor action adaptation.
AB  - A long standing debate revolves around the question whether visual action
      recognition primarily relies on visual or motor action information. Previous
      studies mainly examined the contribution of either visual or motor information to
      action recognition. Yet, the interaction of visual and motor action information
      is particularly important for understanding action recognition in social
      interactions, where humans often observe and execute actions at the same time.
      Here, we behaviourally examined the interaction of visual and motor action
      recognition processes when participants simultaneously observe and execute
      actions. We took advantage of behavioural action adaptation effects to
      investigate behavioural correlates of neural action recognition mechanisms. In
      line with previous results, we find that prolonged visual exposure (visual
      adaptation) and prolonged execution of the same action with closed eyes (non
      visual motor adaptation) influence action recognition. However, when participants
      simultaneously adapted visually and motorically - akin to simultaneous execution
      and observation of actions in social interactions - adaptation effects were only
      modulated by visual but not motor adaptation. Action recognition, therefore,
      relies primarily on vision-based action recognition mechanisms in situations that
      require simultaneous action observation and execution, such as social
      interactions. The results suggest caution when associating social behaviour in
      social interactions with motor based information. 

PMID- 27029782
TI  - Enhancement of Lateral Diffusion in Catanionic Vesicles during Multilamellar-to
      Unilamellar Transition.
AB  - Catanionic vesicles are formed spontaneously by mixing cationic and anionic
      dispersions in aqueous solution in suitable conditions. Because of spontaneity in
      formation, long-term stability, and easy modulation of size and charge, they have
      numerous advantages over conventional lipid-based vesicles. The dynamics of such
      vesicles is of interest in the field of biomedicine, as they can be used to
      deliver drug molecules into the cell membrane. Dynamics of catanionic vesicles
      based on sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB)
      have been studied using incoherent elastic and quasielastic neutron scattering
      (QENS) techniques. Neutron scattering experiments have been carried out on two
      backscattering spectrometers, IRIS and IN16B, which have different energy
      resolutions and energy transfer windows. An elastic fixed-window scan carried out
      using IN16B shows a phase transition at ~307 K during the heating cycle, whereas
      on cooling the transition occurred at ~294 K. DSC results are found to be in
      close agreement with the elastic scan data. This transition is ascribed to a
      structural rearrangement from a multilamellar to a unilamellar phase [ Andreozzi
      J. Phys. Chem. B 2010 , 114 , 8056 - 8060 ]. It is found that a model in which
      the surfactant molecules undergo both lateral and internal motions can describe
      the QENS data quite well. While the data from IRIS have contributions from both
      dynamical processes, the data from IN16B probe only lateral motions, as the
      internal motions are too fast for the energy window of the spectrometer. It is
      found that, through the transition, the fraction of surfactant molecules
      undergoing lateral motion increases of a factor of 2 from the multilamellar to
      the unilamellar phase, indicating an enhanced fluidity of the latter. The lateral
      motion is found to be Fickian in nature, while the internal motion has been
      described by a localized translational diffusion model. The results reported here
      could have direct interest for a number of applications, such as molecular
      transport, and the effect of specific drug molecules or hormones through the
      membrane.

PMID- 27029783
TI  - How to evaluate BP measurements using the oscillometric method in atrial
      fibrillation: the value of pulse rate variation.
AB  - An oscillometric device is recommended for blood pressure (BP) measurement in
      atrial fibrillation (AF), but there is still controversy concerning its accuracy.
      Therefore, evaluation of BP values in AF patients remains a challenge. This study
      included 251 patients with AF and 154 participants with sinus rhythm (SR). Pulse
      rate (PR) and BP were measured using an oscillometric device three times. The
      differences between the highest and lowest PR and the systolic and diastolic BP
      (SBP and DBP) were calculated as DeltaPR, DeltaSBP and DeltaDBP, respectively. AF
      patients were stratified with respect to DeltaPR in 0-5, 6-10, 11-15 and >15
      subgroups. The AF group had a greater DeltaPR (12.1+/-8.6 vs. 4.10+/-3.21 b.p.m.,
      P<0.001), DeltaSBP and DeltaDBP than the SR group at similar SBP and DBP. A
      positive correlation existed between DeltaPR and DeltaSBP (r=0.255, P<0.001) in
      AF patients, but no correlation was found in SR subjects. Meanwhile, the DeltaSBP
      in the 0-5 and 6-10 subgroups (9.58+/-5.61 and 10.67+/-6.77 vs. 8.45+/-5.25 mm
      Hg, nonsignificant) was similar to the SR group, whereas DeltaSBP in the 11-15
      and >15 subgroups was significantly greater than the SR group. Regardless of
      DeltaPR, the DeltaDBP in the AF group was significantly greater than that of the
      SR group. The AF patients who exhibited greater variability in their PR also had
      a greater variability in their SBP readings. The SBP measurement for AF patients
      is accurate as the measurement for patients with SR if the DeltaPR is of 0-10
      b.p.m. in AF. 

PMID- 27029784
TI  - Unlocking the Black Box: A Multilevel Analysis of Preadolescent Children's
      Coping.
AB  - This random assignment experimental study examined the intersection of children's
      coping and physiologic stress reactivity and recovery patterns in a sample of
      preadolescent boys and girls. A sample of 82 fourth-grade and fifth-grade (Mage =
      10.59 years old) child-parent dyads participated in the present study. Children
      participated in the Trier Social Stress Test and were randomly assigned to one of
      two post-Trier Social Stress Test experimental coping conditions-behavioral
      distraction or cognitive avoidance. Children's characteristic ways of coping were
      examined as moderators of the effect of experimental coping condition on cortisol
      reactivity and recovery patterns. Multilevel modeling analyses indicated that
      children's characteristic coping and experimental coping condition interacted to
      predict differential cortisol recovery patterns. Children who characteristically
      engaged in primary control engagement coping strategies were able to more quickly
      down-regulate salivary cortisol when primed to distract themselves than when
      primed to avoid, and vice versa. The opposite pattern was true for characteristic
      disengagement coping in the context of coping condition, suggesting that
      regulatory fit between children's characteristic ways of coping and cues from
      their coping environment may lead to more and less adaptive physiologic recovery
      profiles. This study provides some of the first evidence that coping "gets under
      the skin" and that children's characteristic ways of coping may constrain or
      enhance a child's ability to make use of environmental coping resources.

PMID- 27029785
TI  - Prevalence and Risk Factors of Carotid Plaque Among Middle-aged and Elderly
      Adults in Rural Tianjin, China.
AB  - Carotid plaque (CP) is associated with cardiovascular and cerebrovascular events.
      However, population-based studies with a large sample are rare in China,
      particularly those in the low-income population. We aimed to determine the
      prevalence of CP and the associated risk factors in the rural areas of northern
      China. Between April 2014 and June 2014, we recruited 3789 residents aged >=45
      years. B-mode ultrasonography was performed to measure the extent of CP. The
      prevalence of CP was 40.3% overall, 47.1% in men, and 35.4% in women (P < 0.001).
      The prevalence of CP increased with increasing age (P < 0.001). The participants
      with CP were more likely to have hypertension, diabetes, high total cholesterol
      (TC) levels, and high low-density lipoprotein-cholesterol levels and be a current
      smoker; however, they were less likely to be obese. Multiple logistic regression
      analysis, adjusted for confounders, indicated that age, male sex, hypertension,
      diabetes, current smoking, and high LDL-C levels were the independent risk
      factors for CP. There was a lower risk of CP with alcohol consumption. The
      findings suggest that managing the conventional risk factors is crucial to reduce
      the burden of cardiovascular and cerebrovascular diseases in the low-income
      population in China. 

PMID- 27029786
TI  - Quadrivalent HPV vaccine safety review and safety monitoring plans for nine
      valent HPV vaccine in the United States.
AB  - Quadrivalent human papillomavirus (4vHPV) vaccine was licensed for use in the
      United States in 2006 and through 2015 was the predominate HPV vaccine used. With
      the exception of syncope, a known preventable adverse event after any injected
      vaccination, both pre-licensure and post-licensure 4vHPV safety data have been
      reassuring with no confirmed safety signals identified. Nine-valent HPV vaccine
      (9vHPV) was licensed in 2014. This review includes post-licensure 4vHPV safety
      findings published to date that have informed the US vaccination program; these
      data will inform US safety monitoring and evaluation for 9vHPV.

PMID- 27029788
TI  - Greece giving up on tobacco control.

PMID- 27029789
TI  - Li7La3Zr2O12 Interface Modification for Li Dendrite Prevention.
AB  - Al-contaminated Ta-substituted Li7La3Zr2O12 (LLZ:Ta), synthesized via solid-state
      reaction, and Al-free Ta-substituted Li7La3Zr2O12, fabricated by hot-press
      sintering (HP-LLZ:Ta), have relative densities of 92.7% and 99.0%, respectively.
      Impedance spectra show the total conductivity of LLZ:Ta to be 0.71 mS cm(-1) at
      30  degrees C and that of HP-LLZ:Ta to be 1.18 mS cm(-1). The lower total
      conductivity for LLZ:Ta than HP-LLZ:Ta was attributed to the higher grain
      boundary resistance and lower relative density of LLZ:Ta, as confirmed by their
      microstructures. Constant direct current measurements of HP-LLZ:Ta with a current
      density of 0.5 mA cm(-2) suggest that the short circuit formation was neither due
      to the low relative density of the samples nor the reduction of Li-Al glassy
      phase at grain boundaries. TEM, EELS, and MAS NMR were used to prove that the
      short circuit was from Li dendrite formation inside HP-LLZ:Ta, which took place
      along the grain boundaries. The Li dendrite formation was found to be mostly due
      to the inhomogeneous contact between LLZ solid electrolyte and Li electrodes. By
      flatting the surface of the LLZ:Ta pellets and using thin layers of Au buffer to
      improve the contact between LLZ:Ta and Li electrodes, the interface resistance
      could be dramatically reduced, which results in short-circuit-free cells when
      running a current density of 0.5 mA cm(-2) through the pellets. Temperature
      dependent stepped current density galvanostatic cyclings were also carried out to
      determine the critical current densities for the short circuit formation. The
      short circuit that still occurred at higher current density is due to the
      inhomogeneous dissolution and deposition of metallic Li at the interfaces of Li
      electrodes and LLZ solid electrolyte when cycling the cell at large current
      densities.

PMID- 27029790
TI  - Training mid-level health cadres to improve health service delivery in rural
      Bangladesh.
AB  - Introduction In recent years, the government of Bangladesh has encouraged private
      sector involvement in producing mid-level health cadres including Medical
      Assistants (MAs). The number of MAs produced has increased significantly. We
      assessed students' characteristics, educational services, competencies and
      perceived attitudes towards health service delivery in rural areas. METHODS: We
      used a mixed method approach using quantitative (questionnaire survey) and
      qualitative (key informant interviews and roundtable discussion) methods.
      Altogether, five public schools with 238 students and 30 private schools with 732
      students were included. Statistical analyses were performed using STATA v-12.
      Qualitative data were analyzed thematically. Findings The majority of the
      students in both public (66%) and private medical assistant training schools
      (MATS) (61%) were from rural backgrounds. They spent the majority of their time
      in classroom learning (public 45% versus private 42%) and the written essay exam
      was the common form of a students' performance assessment. Compared with students
      of public MATS, students of private MATS were more confident in different aspects
      of educational areas, including managing emerging health needs (P<0.001);
      evidence-based practice (P=0.002); critical thinking and problem solving
      (P=0.02), and use of IT/computer skills (P<0.001). Students were aware of not
      having adequate facilities in rural areas (public 71%, private 65%), but they
      perceived working in rural areas will offer several benefits, including use of
      learnt skills; friendly rural people; and opportunities for real-life problem
      solving, etc. CONCLUSION: This study provides a current picture of MATS students'
      characteristics, educational services, competencies and perception towards
      working in rural areas. The MA students in both private and public sectors showed
      a greater level of willingness to serve in rural health facilities. The results
      are promising to improve health service delivery, particularly in rural and hard
      to-reach areas of Bangladesh.

PMID- 27029791
TI  - Pin1 is related with clinical stage of papillary thyroid carcinoma.
AB  - BACKGROUND: The context and aim of this article was to investigate whether the
      expression level of Pin1 was in association with the clinical stage of papillary
      thyroid carcinomas. METHODS: Seventy-two patients who had been treated at the
      Affiliated Hospital of Qingdao University - Yantai YuHuangDing Hospital during
      January 2013 to December 2014 were rolled in. The expression levels of Pin1 using
      immunohistochemistry were tested and were divided into four groups according to
      the different clinical stages and final scores based on multiplying intensity and
      percentage value of IHC results. Data was analyzed with SPSS 20.0, and P value
      <0.05 had been chosen as significant. RESULTS: Considered from analysis result,
      the Pin1 expression status statistically significantly correlated with the PTC
      clinical stages (chi(2) = 8.128, P = 0.043); as the clinical stage proceeded, the
      intensity of Pin1 in PTC cells had been increased. But we did not find any
      relationships between immunohistochemical staining results and other
      clinicopathological characteristics. CONCLUSIONS: The PTC cells' intensity of
      Pin1 was in association with the clinical stage. The role played by Pin1 in PTC
      has been studied, and we need to further investigate the application of Pin1 in
      the treatment of PTC.

PMID- 27029792
TI  - Spontaneous Oligomerization of Nucleotide Alternatives in Aqueous Solutions.
AB  - On early Earth, a primitive polymer that could spontaneously form from likely
      available precursors may have preceded both RNA and DNA as the first genetic
      material. Here, we report that heated aqueous solutions containing 5
      hydroxymethyluracil (HMU) result in oligomers of uracil, heated solutions
      containing 5-hydroxymethylcytosine (HMC) result in oligomers of cytosine, and
      heated solutions containing both HMU and HMC result in mixed oligomers of uracil
      and cytosine. Oligomerization of hydroxymethylated pyrimidines, which may have
      been abundant on the primitive Earth, might have been important in the
      development of simple informational polymers.

PMID- 27029793
TI  - Proton-Induced Collisions on Potential Prebiotic Species.
AB  - With regard to the fascinating question of the origin of life, special interest
      has been devoted to potential prebiotic molecules which could drive the emergence
      of life. In the widely discussed hypothesis of a possible exogen apparition of
      life, the transport of those prebiotic species and their survival under spatial
      conditions is of strong interest. In particular their stability under solar
      radiation or in collisions with bare nucleus has to be considered. In that sense,
      taking account of the abundance of protons in ionized clouds of the interstellar
      medium, we have developed a detailed theoretical study of the charge transfer
      collision dynamics induced by impact of protons on a series of possible prebiotic
      compounds. Three main types of molecules have been considered: first of all the
      DNA and RNA building blocks with on a one hand the nucleobases uracil and
      thymine, and on the other hand the 2-deoxy-D-ribose sugar skeleton in its
      furanose and pyranose forms. The study has been extended to the 2-aminooxazole
      suggested to be a possible precursor of RNA nucleotides. The theoretical
      treatment involves ab-initio quantum chemistry molecular calculations followed by
      a semiclassical collision dynamics. Some qualitative trends may be suggested for
      the proton-induced damage of such prebiotic species.

PMID- 27029794
TI  - Indicators and Methods to Understand Past Environments from ExoMars Rover Drills.
AB  - Great advances are expected during the analysis of drilled material acquired from
      2 m depth by ExoMars rover, supported by the comparison to local context, and the
      joint use of different instruments. Textural information might be less detailed
      relatively to what is usually obtained at outcrops during classical geological
      field work on the Earth, partly because of the lack of optical imaging of the
      borehole wall and also because the collected samples are crushed. However sub-mm
      scale layering and some other sedimentary features might be identified in the
      borehole wall observations, or in the collected sample prior to crushing, and
      also at nearby outcrops. The candidate landing sites provide different targets
      and focus for research: Oxia Planum requires analysis of phyllosilicates and OH
      content, at Mawrth Vallis the layering of various phyllosilicates and the role of
      shallow-subsurface leaching should be emphasized. At Aram Dorsum the particle
      size and fluvial sedimentary features will be interesting. Hydrated perchlorates
      and sulphates are ideal targets possibly at every landing sites because of OH
      retention, especially if they are mixed with smectites, thus could point to even
      ancient wet periods. Extensive use of information from the infrared wall scanning
      will be complemented for geological context by orbital and rover imaging of
      nearby outcrops. Information from the context is especially useful to infer the
      possible action of past H2O. Separation of the ice and liquid water effects will
      be supported by cation abundance and sedimentary context. Shape of grains also
      helps here, and composition of transported grains points to the weathering
      potential of the environment in general. The work on Mars during the drilling and
      sample analysis will provide brand new experience and knowledge for future
      missions.

PMID- 27029795
TI  - Reflected Light from Giant Planets in Habitable Zones: Tapping into the Power of
      the Cross-Correlation Function.
AB  - The direct detection of reflected light from exoplanets is an excellent probe for
      the characterization of their atmospheres. The greatest challenge for this task
      is the low planet-to-star flux ratio, which even in the most favourable case is
      of the order of 10-4 in the optical. This ratio decreases even more for planets
      in their host's habitable zone, typically lower than 10-7. To reach the signal-to
      noise level required for such detections, we propose to unleash the power of the
      Cross Correlation Function in combination with the collecting power of next
      generation observing facilities. The technique we propose has already yielded
      positive results by detecting the reflected spectral signature of 51 Pegasi b
      (see Martins et al. 2015). In this work, we attempted to infer the number of
      hours required for the detection of several planets in their host's habitable
      zone using the aforementioned technique from theoretical EELT observations. Our
      results show that for 5 of the selected planets it should be possible to directly
      recover their reflected spectral signature.

PMID- 27029796
TI  - Sorafenib Decreases Tumor Exposure to an Anti-carcinoembryonic Antigen Monoclonal
      Antibody in a Mouse Model of Colorectal Cancer.
AB  - In this investigation, we test the hypothesis that treatment with sorafenib, an
      anti-angiogenic agent, decreases tumor vascularization and, consequently, hinders
      the delivery of monoclonal antibodies (mAb) to xenograft tumors. Severe combined
      immunodeficiency mice bearing carcinoembryonic antigen (CEA) expressing tumor
      xenografts were divided into control and sorafenib-treated groups. Sorafenib was
      administered to the latter group at 50 mg/kg IP every 48 h, starting 4 days post
      tumor implantation. When tumors attained a size of 200-300 mm(3), mice were
      evaluated for (a) tumor microvessel density (using immunohistochemical analysis),
      (b) tumor macromolecular extravasation (using Evans Blue Dye (EBD)), (c)
      pharmacokinetics of an anti-CEA mAb, T84.66, following an intravenous dose of 10
      mg/kg, and (d) intra-tumoral spatial distribution of T84.66 (using
      autoradiography). Sorafenib treatment resulted in a substantial reduction in
      tumor growth rate, a visible reduction in tumor microvessel density, and in a
      46.4% decrease in EBD extravasation in tumor tissue (p < 0.0455). For control and
      treated mice, no significant difference was found for the area under the mAb
      plasma concentration-time curve (AUC(0-7d): 1.67 * 10(3) +/- 1.28 * 10(2) vs.
      1.76 * 10(3) +/- 1.75 * 10(2) nM * day, p = 0.51). However, tumor AUC(0-7d) was
      reduced by 40.8% in sorafenib-treated mice relative to that observed in control
      mice (5.61 * 10(2) +/- 4.27 * 10(1) vs. 9.48 * 10(2) +/- 5.61 * 10(1) nM * day, p
      < 0.001). Sorafenib therapy was also found to markedly alter mAb tumor spatial
      distribution. The results collectively suggest that sorafenib treatment causes a
      significant reduction in mAb delivery to, and distribution within, solid tumors.

PMID- 27029797
TI  - Evolution of Antibody-Drug Conjugate Tumor Disposition Model to Predict
      Preclinical Tumor Pharmacokinetics of Trastuzumab-Emtansine (T-DM1).
AB  - A mathematical model capable of accurately characterizing intracellular
      disposition of ADCs is essential for a priori predicting unconjugated drug
      concentrations inside the tumor. Towards this goal, the objectives of this
      manuscript were to: (1) evolve previously published cellular disposition model of
      ADC with more intracellular details to characterize the disposition of T-DM1 in
      different HER2 expressing cell lines, (2) integrate the improved cellular model
      with the ADC tumor disposition model to a priori predict DM1 concentrations in a
      preclinical tumor model, and (3) identify prominent pathways and sensitive
      parameters associated with intracellular activation of ADCs. The cellular
      disposition model was augmented by incorporating intracellular ADC degradation
      and passive diffusion of unconjugated drug across tumor cells. Different
      biomeasures and chemomeasures for T-DM1, quantified in the companion manuscript,
      were incorporated into the modified model of ADC to characterize in vitro
      pharmacokinetics of T-DM1 in three HER2+ cell lines. When the cellular model was
      integrated with the tumor disposition model, the model was able to a priori
      predict tumor DM1 concentrations in xenograft mice. Pathway analysis suggested
      different contribution of antigen-mediated and passive diffusion pathways for
      intracellular unconjugated drug exposure between in vitro and in vivo systems.
      Global and local sensitivity analyses revealed that non-specific deconjugation
      and passive diffusion of the drug across tumor cell membrane are key parameters
      for drug exposure inside a cell. Finally, a systems pharmacokinetic model for
      intracellular processing of ADCs has been proposed to highlight our current
      understanding about the determinants of ADC activation inside a cell.

PMID- 27029798
TI  - Thrombosed external hemorrhoids in pregnancy: a retrospective review of outcomes.

PMID- 27029799
TI  - Short-term mortality, readmission, and recurrence in treatment of acute
      diverticulitis with abscess formation: a nationwide register-based cohort study.
AB  - PURPOSE: The aim of the study was to investigate short-term mortality,
      readmission, and recurrence in a national cohort of patients with Hinchey Ib-II
      diverticulitis. METHODS: The retrospective cohort-investigation was conducted
      using a database consisting of the entire Danish population (n = 6,641,672) in
      year 2000-2012, formed by linking the Danish Registers. Patients admitted with
      acute Hinchey Ib-II diverticulitis were identified from ICD-10 discharge codes
      and stratified according to treatment into an operative, drainage, and
      antibiotics group. The primary outcome was 30-day mortality from admission,
      secondary outcomes were mortality, readmission, and recurrence within 30 days
      post-discharge. The study was reported using RECORD guidelines. RESULTS: A total
      of 3148 eligible patients were identified. The cohort had a mean age of 65.1
      year, 25.6 % had previously been admitted with diverticulitis, and 48.1 % had
      registered comorbidities. Within 30 days from admission, 8.7 % of the patients
      died. Of patients discharged, 2.5 % died, 23.8 % was readmitted, and 5.9 % was
      readmitted due to diverticulitis within 30 days from discharge. In multivariate
      analyses, increasing age was associated with mortality at odds-ratio (95 % CI)
      1.10 (1.09-1.12). Previous complicated and uncomplicated diverticulitis reduced
      mortality with odds-ratio 0.50 (0.33-0.76) and 0.73 (0.58-0.92), while
      uncomplicated diverticulitis also increased risk of recurrence with odds-ratio
      1.51 (1.24-1.84). Glucocorticoid usage was associated with mortality with odds
      ratio 1.49 (1.23-1.81) and readmission with odds-ratio 2.91 (1.24-6.80).
      CONCLUSION: Acute diverticulitis with abscess formation is a severe and life
      threatening condition. Direct comparisons of treatment groups were not possible
      due to possible confounding by indication.

PMID- 27029800
TI  - The use of trauma interprofessional simulated education (TIPSE) to enhance role
      awareness in the emergency department setting.
AB  - Interprofessional simulation-based education (IPSE) is common in medicine and
      nursing curricula, however, less evident in diagnostic radiography. Previous work
      suggests graduate radiographers are unprepared in terms of trauma knowledge and
      experience. A trauma IPSE programme as a joint venture between two universities
      was developed. Our aim was to explore the views of radiography, nursing, and
      medical students regarding preparedness for trauma practice. Second-year
      radiography (n = 39), nursing (n = 10), and medical (n = 5) students were invited
      to participate in trauma simulations. Pre- and post-scenario questionnaires were
      completed and quantitative analysis undertaken. Prior to IPSE, the majority of
      students were unprepared to manage trauma. Post-scenario felt significantly more
      prepared to undertake their role in the team and had better understanding of
      their and other professions' roles in trauma (P < 0.01). IPSE is an effective
      means of preparing undergraduate students in understanding both their and other
      professional's roles within the trauma team. 

PMID- 27029801
TI  - Atraumatic Restorative Treatment compared to the Hall Technique for occluso
      proximal cavities in primary molars: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: In many parts of the world, school-age children have high dental
      treatment needs; however, there is often low, or no, dental care provision.
      Although Atraumatic Restorative Treatment (ART) was developed to address this,
      its survival rate in occluso-proximal lesions is low. An alternative, the Hall
      Technique (HT) has shown better relative outcomes for occluso-proximal lesions,
      but has not been directly compared to ART or tested in field settings. This trial
      will compare ART and the HT for the most clinically- and cost-effective strategy
      for managing occluso-proximal lesions in primary molars, in a school setting,
      using low-technology and child-friendly dental techniques. METHODS/DESIGN: This
      two-arm, parallel group, patient-randomized controlled, superiority trial will
      have treatment provided in schools. Schoolchildren (n = 124, age 6-8) with at
      least one occluso-proximal carious primary molar lesion will have random
      allocation to treatment with ART or HT. Baseline measures and outcome data will
      be assessed through participant report, clinical examination and parent
      report/questionnaires. The primary outcome is survival rate, a composite measure
      of absence of Minor Failures (a defect in the restoration/crown, but not
      interfering with tooth health) and Major Failures (signs or symptoms of
      irreversible pulp damage, such as dental fistula/abscess, tooth fracture or
      failures that cannot be repaired). Secondary outcomes are: (1) child-reported
      discomfort, (2) childrens' and (3) parents' concerns around dental appearance and
      (4) acceptability of treatments, (5) occlusal-vertical dimensions (OVD) changes,
      (6) plaque index, (7) gingival health, (8) decayed, missing, filled teeth in
      permanent teeth (DMFT)/decayed, missing, filled teeth in primary teeth (dmft),
      (9) oral health-related-quality of life, reported by children and
      parents/caregivers, (10) the incremental cost-effectiveness, and (11) operator
      effect. A trained and calibrated examiner will evaluate the treated teeth after 1
      week, then 1, 6, 12, 24 and 36 months post treatment. Kaplan-Meier and Cox
      regression tests will be used to investigate the primary outcome. The Mann
      Whitney or t test, Friedman test, paired t test or Wilcoxon test and Ordinal
      Logistic Regression Analysis will be used to analyze the secondary outcomes.
      DISCUSSION: The results of this trial will support decision-making by clinicians
      and policy-makers for managing occluso-proximal lesions in settings with
      constrained resources and limited dental access. TRIAL REGISTRATION:
      www.clinicaltrials.gov, NCT02569047 , registered 5 October 2015.

PMID- 27029803
TI  - Furthering our understanding of SUDEP: the role of animal models.
AB  - Sudden and unexpected death in epilepsy (SUDEP) is the most common type of death
      among patients with epilepsy. Here, we address the importance of the experimental
      models in search of the mechanisms underlying SUDEP. Most studies have
      investigated the cardiovascular responses in animal models of epilepsy. However,
      there are few proposed SUDEP models in literature. Hypoventilation, apnea,
      respiratory distress, pulmonary hypertension, autonomic dysregulation and
      arrhythmia are common findings in epilepsy models. Impairments on adenosinergic
      and serotonergic systems, brainstem spreading depolarization, seizure-activation
      of neural substrates related to cardiorespiratory control, altered autonomic
      control, and mutations on sodium and potassium channels are hypothesis suggested.
      Overall, current research highlights the evident multifactorial nature of SUDEP,
      which involves acute and chronic aspects ranging from systemic to molecular
      alterations. Thus, we are convinced that elucidation and prevention of SUDEP can
      be achieved only through the interaction between basic and clinical science.

PMID- 27029804
TI  - Arthroscopic debridement of the ankle for mild to moderate osteoarthritis: a
      midterm follow-up study in former professional soccer players.
AB  - BACKGROUND: The aim of this study is to report the clinical and functional
      outcomes following arthroscopic management of anterior impingement, grade III-IV
      cartilage lesions, and mild to moderate osteoarthritis of the ankle in former
      soccer players. METHODS: The study included 15 former male professional soccer
      players with mild to moderate degenerative changes of the ankle who had undergone
      arthroscopic debridement and management of secondary injuries of the ankle.
      Preoperatively and at the last follow-up, at an average of 7.4 years, the
      American Orthopaedic Foot and Ankle Society (AOFAS) and the Kaikkonen scales and
      visual analogue scale (VAS) assessment were administered to all patients. Ankle
      osteoarthritis was assessed from weightbearing anteroposterior and lateral
      radiographs of both ankles. RESULTS AND DISCUSSION: At the last follow-up, the
      average AOFAS score had increased significantly from 48 (range, 29-69) to 86
      (range, 63-94) (P < 0.0001), with good to excellent scores in 11 patients (74 %).
      The average Kaikkonen preoperative score of 43 (range, 28-70) had significantly
      improved to 85 (range, 61-95) (P < 0.0001), with good excellent scores in 11
      patients (74 %). VAS values were also improved at the last follow-up. At the last
      appointment, only one (7 %) patient had abandoned altogether any sport, as he did
      not feel safe with his ankle and he felt too old to continue. CONCLUSIONS:
      Anterior ankle arthroscopy for management of mild to moderate ankle arthritis is
      safe, effective, and low cost and allows former athletes to safely return to
      ordinary daily activities and recreational sport activities.

PMID- 27029805
TI  - Concordance between core needle biopsy and surgical specimen for oestrogen
      receptor, progesterone receptor and human epidermal growth factor receptor 2
      status in breast cancer.
AB  - INTRODUCTION: This study aimed to analyse the concordance rate, sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value of
      core needle biopsy (CNB) and subsequent surgical specimen (SS) in assessing
      levels of oestrogen receptor (ER), progesterone receptor (PgR) and human
      epidermal growth factor receptor 2 (HER2/neu). It also evaluated the revised
      American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP)
      guidelines for ER/PgR positivity. METHODS: We analysed the breast cancer database
      of KK Women's and Children's Hospital, Singapore, from 1 June 2005 to 30 December
      2012. Invasive breast cancer patients who had CNB and subsequent SS were
      included. RESULTS: A total of 560 patients were included. The concordance of ER,
      PgR and HER2/neu positivity between CNB and SS was 96.1%, 89.1% and 96.8%,
      respectively. When the 'ER >= 10% positive' group was compared with the 'ER >= 1%
      positive' group, specificity increased from 79.7% to 92.5% and PPV increased from
      93.9% to 97.5%. When the 'PgR >= 10% positive' group was compared with the 'PgR
      >= 1% positive' group, specificity increased from 84.2% to 89.3% and PPV improved
      from 89.7% to 92.9%. The revised ASCO/CAP guidelines decreased discordant results
      by > 50% for ER and by 18.2% for PgR. CONCLUSION: CNB has high concordance with
      SS in the evaluation of the molecular profile of invasive breast cancer. Thus,
      molecular evaluation does not need to be repeated with SS except for ER-, PgR-
      and HER2/neu-negative CNB results. The revised ASCO/CAP guidelines resulted in
      more precise ER and PgR status on CNB.

PMID- 27029806
TI  - Clinical characteristics and rehabilitation of hospitalised cancer patients in a
      Korean tertiary hospital.
AB  - INTRODUCTION: With the increase in the patient survival rates of many types of
      cancers, a greater proportion of cancer patients live with disease-related
      problems that diminish their quality of life. This study aimed to investigate the
      clinical characteristics and rehabilitation of hospitalised cancer patients who
      were referred to the Department of Physical and Rehabilitation Medicine (PRM) at
      Samsung Medical Center, a tertiary university hospital in Seoul, Korea. METHODS:
      Hospitalised cancer patients aged > 18 years who were referred to the Department
      of PRM from January to December 2012 were enrolled in this retrospective study.
      We reviewed the clinical characteristics of the patients, the principal reasons
      for their referral and relevant details of their rehabilitative management.
      RESULTS: A total of 1,340 cases were included. The most common primary cancer was
      lung cancer (19.0%) and 28.6% of the cases had solid organ metastasis. The most
      common reason for referral was deconditioning (31.7%), followed by weakness
      (23.1%) and respiratory problems (14.5%). Bedside exercise was prescribed to
      28.4% of the patients, exercise in the rehabilitation therapy unit to 28.0% and
      pulmonary rehabilitation to 14.3%. Among the 1,340 cases, 107 (8.0%) were
      transferred to the Department of PRM for comprehensive rehabilitation. The 32
      patients with an identifiable Modified Barthel Index score showed significant
      functional improvement. CONCLUSION: The findings of the present study contribute
      to a better understanding of rehabilitation for hospitalised cancer patients. The
      information obtained will also be helpful in the development of appropriate
      cancer rehabilitation strategies.

PMID- 27029807
TI  - The predictive value of early molecular response in chronic myeloid leukaemia
      patients treated with imatinib in a single real-world medical centre in a
      developing country.
AB  - INTRODUCTION: The prognosis of patients with chronic myeloid leukaemia (CML) has
      improved since the introduction of imatinib. However, patients who do not achieve
      complete cytogenetic response (CCyR) and major molecular response (MMR) have
      poorer prognosis. Recent clinical trials have demonstrated that early and deeper
      cytogenetic and molecular responses predict a better long-term outcome. This
      study aimed to analyse the relationship between early molecular response and
      clinical outcome in a real-life setting. METHODS: This retrospective study
      included all patients with CML, in chronic or accelerated phase, who were treated
      with imatinib at University of Malaya Medical Centre, Malaysia. RESULTS: A total
      of 70 patients were analysed. The median follow-up duration was 74 months, and
      the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%,
      respectively. Overall survival (OS) and event-free survival (EFS) at ten years
      were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had
      significantly better OS and EFS than those who did not. At six months, patients
      who had a BCR-ABL level <= 10% had significantly better OS and EFS than those who
      had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at
      18 months showed no survival advantage in our patients. CONCLUSION: Our data
      showed that imatinib is still useful as first-line therapy. However, vigilant
      monitoring of patients who have a BCR-ABL level > 10% at six months of treatment
      should be implemented so that prompt action can be taken to provide the best
      outcome for these patients.

PMID- 27029808
TI  - Radiologic-pathologic correlation of orbital diseases.

PMID- 27029809
TI  - The Use of Perinatal 6-Hydroxydopamine to Produce a Rodent Model of Lesch-Nyhan
      Disease.
AB  - Lesch-Nyhan disease is a neurologically, metabolically, and behaviorally
      devastating condition that has eluded complete characterization and adequate
      treatment. While it is known that the disease is intimately associated with
      dysfunction of the hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene that
      codes for an enzyme of purine metabolism (hypoxanthine-guanine
      phosphoribosyltransferase) and is associated with neurological, behavioral, as
      well as metabolic dysfunction, the mechanisms of the neurobehavioral
      manifestations are as yet unclear. However, discoveries over the past few decades
      not only have created useful novel animal models (e.g., the HPRT-deficient mouse
      and the serendipitously discovered perinatal 6-hydroxydopamine (6-OHDA lesion
      model), but also have expanded into epigenetic, genomic, and proteomic approaches
      to better understand the mechanisms underlying this disease. The perinatal 6-OHDA
      model, in addition to modeling self-injury and dopamine depletion in the clinical
      condition, also underscores the profound importance of development in the
      differential course of maladaptive progression in the face of a common/single
      neurotoxic insult at different ages. Recent developments from clinical and basic
      science efforts attest to the fact that while the disease would seem to have a
      simple single gene defect at its core, the manifestations of this defect are
      profound and unexpectedly diverse. Future efforts employing the 6-OHDA model and
      others in the context of the novel technologies of genome editing, chemo- and
      opto-genetics, epigenetics, and further studies on the mechanisms of stress
      induced maladaptations in brain all hold promise in taking our understanding of
      this disease to the next level. 

PMID- 27029810
TI  - Variants near CHRNA3/5 and APOE have age- and sex-related effects on human
      lifespan.
AB  - Lifespan is a trait of enormous personal interest. Research into the biological
      basis of human lifespan, however, is hampered by the long time to death. Using a
      novel approach of regressing (272,081) parental lifespans beyond age 40 years on
      participant genotype in a new large data set (UK Biobank), we here show that
      common variants near the apolipoprotein E and nicotinic acetylcholine receptor
      subunit alpha 5 genes are associated with lifespan. The effects are strongly sex
      and age dependent, with APOE E4 differentially influencing maternal lifespan
      (P=4.2 * 10(-15), effect -1.24 years of maternal life per imputed risk allele in
      parent; sex difference, P=0.011), and a locus near CHRNA3/5 differentially
      affecting paternal lifespan (P=4.8 * 10(-11), effect -0.86 years per allele; sex
      difference P=0.075). Rare homozygous carriers of the risk alleles at both loci
      are predicted to have 3.3-3.7 years shorter lives. 

PMID- 27029811
TI  - Tarsoaponeurectomy as an alternative in difficult blepharoptosis cases.
AB  - BACKGROUND: The purpose of this study was to evaluate the results of
      tarsoaponeurectomy in patients with unsuccessful results after repetitive surgery
      or who developed post-traumatic blepharoptosis. METHODS: The files of 107
      patients (136 eyes) on whom surgery was performed between January 2010 and
      December 2014 due to blepharoptosis were scanned retrospectively. Among these
      patients, the files and operational notes of eight patients who underwent surgery
      through the method of tarsoaponeurectomy were examined in detail. The
      epidemiological data, indication for surgery, previous ptosis and/or eyelid
      surgeries and trauma histories, preoperative and postoperative measurement data
      (palpebral space (PS), margin reflex distance (MRD1, MRD2), levator muscle
      function (LMF)) of the patients were recorded. The follow-up time of the patients
      was 7 to 34 months with an average of 16 months. RESULTS: A total of eight
      patients consisting of three females and five males were included in the study.
      The age range was 19 to 63 years with an average of 39 +/- 16.2 years. Four
      patients had traumatic ptosis history whereas four patients had previous multiple
      levator procedure surgery history. Those patients with a history of ptosis had
      undergone surgery with levator procedure at least two times. Additionally, one
      patient had upper eyelid entropion, one had anophthalmic socket syndrome, and one
      had exposure keratopathy and traumatic dilated pupil. Seven patients had ptosis
      in the left eye whereas one patient had ptosis in the right eye. All patients
      were given a tarsoaponeurectomy as the basic surgical procedure while the patient
      with entropion was given a tarsal fracture and ear cartilage grafting as
      additional surgery. Two patients with vertical notching were also given a
      vertical blepharotomy through which a strip of tarsus was removed. CONCLUSIONS:
      Tarsoaponeurectomy is an alternative method for oculoplastic surgeons used to
      deal with patients on whom sufficient and desired results have not been achieved
      despite repetitive surgery and in post-traumatic cases where levator muscle and
      aponeurosis cannot be dissociated peroperatively.

PMID- 27029812
TI  - Anatomical and functional gonadotrope networks in the teleost pituitary.
AB  - Mammalian pituitaries exhibit a high degree of intercellular coordination; this
      enables them to mount large-scale coordinated responses to various physiological
      stimuli. This type of communication has not been adequately demonstrated in
      teleost pituitaries, which exhibit direct hypothalamic innervation and expression
      of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in distinct
      cell types. We found that in two fish species, namely tilapia and zebrafish, LH
      cells exhibit close cell-cell contacts and form a continuous network throughout
      the gland. FSH cells were more loosely distributed but maintained some degree of
      cell-cell contact by virtue of cytoplasmic processes. These anatomical
      differences also manifest themselves at the functional level as evidenced by the
      effect of gap-junction uncouplers on gonadotropin release. These substances
      abolished the LH response to gonadotropin-releasing hormone stimulation but did
      not affect the FSH response to the same stimuli. Dye transfer between neighboring
      LH cells provides further evidence for functional coupling. The two gonadotropins
      were also found to be differently packaged within their corresponding cell types.
      Our findings highlight the evolutionary origin of pituitary cell networks and
      demonstrate how the different levels of cell-cell coordination within the LH and
      FSH cell populations are reflected in their distinct secretion patterns. 

PMID- 27029815
TI  - Effectiveness of Telemonitoring in Patients with Chronic Obstructive Pulmonary
      Disease in Taiwan-A Randomized Controlled Trial.
AB  - Chronic obstructive pulmonary disease (COPD) is the leading cause of death
      worldwide, and poses a substantial economic and social burden. Telemonitoring has
      been proposed as a solution to this growing problem, but its impact on patient
      outcome is equivocal. This randomized controlled trial aimed to investigate
      effectiveness of telemonitoring in improving COPD patient outcome. In total, 106
      subjects were randomly assigned to the telemonitoring (n = 53) or usual care (n =
      53) group. During the two months following discharge, telemonitoring group
      patients had to report their symptoms daily using an electronic diary. The
      primary outcome measure was time to first re-admission for COPD exacerbation
      within six months of discharge. During the follow-up period, time to first re
      admission for COPD exacerbation was significantly increased in the telemonitoring
      group than in the usual care group (p = 0.026). Telemonitoring was also
      associated with a reduced number of all-cause re-admissions (0.23 vs.
      0.68/patient; p = 0.002) and emergency room visits (0.36 vs. 0.91/patient; p =
      0.006). In conclusion, telemonitoring intervention was associated with improved
      outcomes among COPD patients admitted for exacerbation in a country characterized
      by a small territory and high accessibility to medical services. The findings are
      encouraging and add further support to implementation of telemonitoring as part
      of COPD care. 

PMID- 27029816
TI  - Participation in communication activities following traumatic brain injury: A
      time use diary study.
AB  - BACKGROUND: Communication impairments following traumatic brain injury (TBI) can
      represent a significant barrier to successful community reintegration. Previous
      research has typically focused on linguistic competence to identify communication
      difficulties experienced by people with TBI living in the community, rather than
      participation in everyday communication activities. OBJECTIVE: To describe
      communication activities and communication partners of people with traumatic
      brain injury (TBI) over a 24-hour period compared to matched controls. RESEARCH
      DESIGN: A cross-sectional study using a customized, mixed-methods survey with
      time-use data collected from people with TBI and a demographically matched
      control group. METHODS: Twenty people with TBI living within the community and 20
      matched non-injured controls were interviewed about their involvement in
      communication activities over the previous 24 hours using a time-use
      diary.Activities were compared between the groups using Mann-Whitney U-tests and
      Chi-squared tests. RESULTS: The TBI group spent significantly less time engaged
      in communication activities and less time engaged in conversation and reported
      significantly fewer numbers of communication partners compared to the control
      group. CONCLUSION: The results highlight discrepancies in participation in
      communication activities between people with TBI and people without TBI,
      suggesting the need for intervention studies to enhance communication
      participation in daily life following TBI.

PMID- 27029813
TI  - Multivariate models from RNA-Seq SNVs yield candidate molecular targets for
      biomarker discovery: SNV-DA.
AB  - BACKGROUND: It has recently been shown that significant and accurate single
      nucleotide variants (SNVs) can be reliably called from RNA-Seq data. These may
      provide another source of features for multivariate predictive modeling of
      disease phenotype for the prioritization of candidate biomarkers. The continuous
      nature of SNV allele fraction features allows the concurrent investigation of
      several genomic phenomena, including allele specific expression, clonal expansion
      and/or deletion, and copy number variation. RESULTS: The proposed software
      pipeline and package, SNV Discriminant Analysis (SNV-DA), was applied on two RNA
      Seq datasets with varying sample sizes sequenced at different depths: a dataset
      containing primary tumors from twenty patients with different disease outcomes in
      lung adenocarcinoma and a larger dataset of primary tumors representing two major
      breast cancer subtypes, estrogen receptor positive and triple negative.
      Predictive models were generated using the machine learning algorithm, sparse
      projections to latent structures discriminant analysis. Training sets composed of
      RNA-Seq SNV features limited to genomic regions of origin (e.g. exonic or
      intronic) and/or RNA-editing sites were shown to produce models with accurate
      predictive performances, were discriminant towards true label groupings, and were
      able to produce SNV rankings significantly different from than univariate tests.
      Furthermore, the utility of the proposed methodology is supported by its
      comparable performance to traditional models as well as the enrichment of
      selected SNVs located in genes previously associated with cancer and genes
      showing allele-specific expression. As proof of concept, we highlight the
      discovery of a previously unannotated intergenic locus that is associated with
      epigenetic regulatory marks in cancer and whose significant allele-specific
      expression is correlated with ER+ status; hereafter named ER+ associated hotspot
      (ERPAHS). CONCLUSION: The use of models from RNA-Seq SNVs to identify and
      prioritize candidate molecular targets for biomarker discovery is supported by
      the ability of the proposed method to produce significantly accurate predictive
      models that are discriminant towards true label groupings. Importantly, the
      proposed methodology allows investigation of mutations outside of exonic regions
      and identification of interesting expressed loci not included in traditional gene
      annotations. An implementation of the proposed methodology is provided that
      allows the user to specify SNV filtering criteria and cross-validation design
      during model creation and evaluation.

PMID- 27029817
TI  - Review: A neglected Flavivirus: an update on Zika virus in 2016 and the future
      direction of research.
AB  - The 2015-16 global emergence of Zika virus infection (ZIKV) and its link with
      Guillain-Barre Syndrome and microcephaly, at the tail-end of the Ebola epidemic,
      has provoked unease throughout the international community. The World Health
      Organisation declared ZIKV a public health emergency on 1st February 2016, but
      until the 31st March 2016 maintained that there was insufficient evidence that
      ZIKV was independently responsible for any serious complications. Our current
      understanding of this arthropod-borne flavivirus is still at an early stage. The
      first reported human infections were 60 years ago, and until the first outbreak
      in Micronesia in 2007, there were only 14 documented cases. Nonetheless, there
      are parallels that we can draw from our understanding of other related arbo
      flaviviruses, such as dengue, Japanese encephalitis and West Nile viruses. This
      article provides a focussed review of the literature on ZIKV to date, with
      perspectives on the direction of future research.

PMID- 27029819
TI  - A Rare Rash in a Pediatric Patient Due to a Very Common Medication.

PMID- 27029818
TI  - Transcriptome analysis in different rice cultivars provides novel insights into
      desiccation and salinity stress responses.
AB  - Drought and salinity are the major environmental factors that affect rice
      productivity. Comparative transcriptome analysis between tolerant and sensitive
      rice cultivars can provide insights into the regulatory mechanisms involved in
      these stress responses. In this study, the comparison of transcriptomes of a
      drought-tolerant [Nagina 22 (N22)] and a salinity-tolerant (Pokkali) rice
      cultivar with IR64 (susceptible cultivar) revealed variable transcriptional
      responses under control and stress conditions. A total of 801 and 507 transcripts
      were exclusively differentially expressed in N22 and Pokkali rice cultivars,
      respectively, under stress conditions. Gene ontology analysis suggested the
      enrichment of transcripts involved in response to abiotic stress and regulation
      of gene expression in stress-tolerant rice cultivars. A larger number of
      transcripts encoding for members of NAC and DBP transcription factor (TF)
      families in N22 and members of bHLH and C2H2 TF families in Pokkali exhibited
      differential regulation under desiccation and salinity stresses, respectively.
      Transcripts encoding for thioredoxin and involved in phenylpropanoid metabolism
      were up-regulated in N22, whereas transcripts involved in wax and terpenoid
      metabolism were up-regulated in Pokkali. Overall, common and cultivar-specific
      stress-responsive transcripts identified in this study can serve as a helpful
      resource to explore novel candidate genes for abiotic stress tolerance in rice. 

PMID- 27029820
TI  - Behavioral Treatment for Headaches in Children: A Practical Guide for the Child
      Psychologist.
AB  - Headache is a highly prevalent condition and is the leading cause for school
      absences. Despite the rich literature supporting behavioral treatments for
      headache, many child psychologists mistakenly perceive that they lack appropriate
      training to treat children with headache. Likewise, many physicians feel
      underprepared to refer the child for behavioral treatments. This article serves
      as a primer, providing tools for the general child psychologist or mental health
      provider by answering frequently asked questions. First, we provide a concise
      background on pathophysiology and medical care for headache. We then detail
      aspects of behavioral interventions for headache, including a case example. We
      included a limited list of up-to-date references most relevant to the child
      psychologist who does not treat headache on a regular basis to support further
      reading. By reviewing this primer, local mental health professionals can provide
      children with headache access to high-quality, evidence-based clinical care
      closer to home.

PMID- 27029821
TI  - E-cigarettes, Hookah Pens and Vapes: Adolescent and Young Adult Perceptions of
      Electronic Nicotine Delivery Systems.
AB  - INTRODUCTION: Most studies have assessed use of "e-cigarettes" or "electronic
      cigarettes," potentially excluding new electronic nicotine delivery systems
      (ENDS), such as e-hookahs and vape pens. Little is known about how adolescents
      and young adults perceive ENDS and if their perceptions vary by sub-type. We
      explored ENDS perceptions among these populations. METHODS: Ten focus groups with
      77 adolescents and young adults, ages 13-25, were conducted in spring 2014.
      Participants were users or susceptible nonusers of novel tobacco products. Focus
      group transcripts were coded for emergent themes. RESULTS: Participants reported
      positive ENDS attributes, including flavor variety; user control of nicotine
      content; and smoke trick facilitation. Negative attributes included different
      feel compared to combustible cigarettes, nicotine addiction potential, and no cue
      to stop use. Participants perceived less harm from ENDS compared to combustible
      cigarettes, perhaps due to marketing and lack of product regulation, but noted
      the uncertainty of ingredients in ENDS. Numerous terms were used to describe
      ENDS, including "e-cigarette," "e-hookah," "hookah pens," "tanks," and "vapes."
      Although no clear classification system emerged, participants used product
      characteristics like nicotine content and chargeability to attempt
      classification. Perceptions differed by product used. E-hookah users were
      perceived as young and trendy while e-cigarette users were perceived as old and
      addicted to nicotine. CONCLUSIONS: Young adults and adolescents report distinct
      ENDS sub-types with varying characteristics and social perceptions of users.
      Although they had more positive than negative perceptions of ENDS, prevention
      efforts should consider highlighting negative attributes as they may discourage
      use and product trial among young nonusers. IMPLICATIONS: Our study underscores
      the need for a standardized measurement system for ENDS sub-types and additional
      research on how ENDS sub-types are perceived among adolescents and young adults.
      In addition, our findings highlight negative product attributes reported by
      participants that may be useful in prevention and regulatory efforts to offset
      favorable marketing messages.

PMID- 27029822
TI  - Using Cognitive Interviewing to Better Assess Young Adult E-cigarette Use.
AB  - INTRODUCTION: Characteristics of electronic nicotine delivery systems (ENDS) make
      assessment of their use a challenge for researchers. Cognitive interviews are a
      way of gaining insight into participants' interpretations of survey questions and
      the methods they use in answering them, to improve survey tools. METHODS: We used
      cognitive interviews to modify a young adult survey and improve assessment of
      quantity and frequency of ENDS use, as well as reasons for initiation and use of
      ENDS products. Twenty-five college students between the ages of 18 and 32
      participated in individual cognitive interviews, which assessed question
      comprehension, answer estimation, retrieval processes, and answer response
      processes. RESULTS: Comprehension issues arose discerning between ENDS device
      types (eg, cigalikes vs. vape pens), and answer estimation issues arose regarding
      ENDS use as drug delivery systems. These issues appeared to improve when pictures
      were added specifying the device in question, as well as when specific language
      naming nicotine as the ENDS product content was added to survey questions.
      Regarding answer retrieval, this sample of users had problems reporting their
      frequency of ENDS use, as well as quantifying the amount of ENDS products
      consumed (eg, volume of e-juice, number of cartridges, nicotine concentration).
      CONCLUSIONS: Accurate assessment of ENDS products proved challenging, but
      cognitive interviews provided valuable insight into survey interpretation that
      was otherwise inaccessible to researchers. Future research that explores how to
      assess the wide array of ENDS devices, as well as possible population differences
      among specific device-type users would be valuable to public health researchers
      and professionals. IMPLICATIONS: This study extends the current literature by
      using cognitive interviews to test ENDS assessment questions in a sample of young
      adults, a population at elevated risk for ENDS use. Problems encountered when
      answering ENDS use questions underscore the need to develop easily understood
      ENDS questions that allow for quantification of ENDS use. Future research
      examining the nature of ENDS product types and different levels of user
      experience will yield valuable assessment tools for researchers and tobacco
      control professionals.

PMID- 27029823
TI  - Effect of Low- and High-Fat Meals on the Pharmacokinetics of Venetoclax, a
      Selective First-in-Class BCL-2 Inhibitor.
AB  - Venetoclax is a selective, first-in-class, B-cell lymphoma-2 inhibitor that has
      demonstrated clinical efficacy in several hematological malignancies. Two studies
      evaluated the relative bioavailability of venetoclax in healthy subjects: (1) a
      bioequivalence study to compare the bioavailability of the film-coated tablet
      with that of an earlier uncoated tablet and (2) a food effect study to evaluate
      the effect of food on venetoclax pharmacokinetics. Both studies were open-label,
      single-dose, crossover studies. In the bioequivalence study, 15 subjects received
      a single dose of venetoclax 50 mg under nonfasting conditions, in each of 2
      periods; one period used the uncoated tablet, and the other used the film-coated
      tablet. In the food effect study, 24 subjects received a single dose of
      venetoclax film-coated 100-mg tablet under fasting conditions, after a low-fat
      breakfast or after a high-fat breakfast in different periods. The venetoclax film
      coated tablet was bioequivalent to the uncoated tablet, which indicates that the
      film coating does not affect bioavailability. The median Tmax of venetoclax was
      delayed by about 2 hours when administered with food. Compared with fasting
      conditions, Cmax and AUC increased by approximately 3.4-fold following a low-fat
      breakfast. High-fat meals increased Cmax and AUC by approximately 50% relative to
      low-fat meals. The mean terminal half-life was comparable between the high-fat
      meal and fasting conditions (19.1 versus 16.1 hours). Based on these results and
      the venetoclax exposure-response profile, venetoclax should be administered with
      food and without specific recommendations for fat content to ensure adequate and
      consistent bioavailability.

PMID- 27029824
TI  - EEG for prognostication in postanoxic coma: what you predict depends on when you
      predict.

PMID- 27029825
TI  - Risk factors for KPC-producing Klebsiella pneumoniae VAP: keep an eye on previous
      therapies!

PMID- 27029826
TI  - Early detection of hypovolemia during the progression of hemorrhage.

PMID- 27029827
TI  - Pax5 Re-expression in H460 Cells Treated with the Combination of Demethylating
      Agent and Histone Deacetylase Inhibitor is Associated with the Enhancement of P53
      Binding to Pax5 Promoter Region.
AB  - BACKGROUND: The epigenetic combinations of DNA demethylating agents and histone
      deacetylase (HDAC) inhibitors have demonstrated clinical benefits for non-small
      cell lung cancer (NSCLC) treatment, however, there are few studies uncovering the
      underlying molecular mechanism of the combinations. Our previous study showed
      that DNA demethylating agent Azacitidine (Aza) demethylated CpG sites in paired
      box gene 5 (pax5) promoter region, but did not induce pax5 mRNA or protein
      expression. METHODS: In this study we used epigenetic combination of Aza and HDAC
      inhibitor Vorinostat (SAHA) to treat NSCLC cells and to elucidate the underlying
      molecular mechanism. We treated pax5- silenced NSCLC H460 cells with Aza+SAHA
      combination at sub-toxic concentration and detected the re-expression of pax5
      mNRA and protein. RESULTS: The results showed demethylation of CpG sites in pax5
      promoter region by Aza treatment and increased DNA accessibility for protein
      binding by SAHA treatment. The combination of Aza+SAHA significantly increased
      p53 protein binding to DNA in pax5 promoter region (p<0.01). More efficient
      binding of the transcription factor p53 to pax5 promoter region is likely because
      SAHA increased accessibility of the chromatin conformation and Aza-demethylated
      DNA was more permissive, allowing transcription factors to bind. CONCLUSION: Our
      study not only explained an underlying mechanism, that pax5 re-expression was
      induced by Aza+SAHA combination in H460 cells via p53, but also demonstrated a
      pattern showing that the combination of demethylating agent and HDAC inhibitor
      can re-activate tumor suppressor gene (TSG) which is associated with the
      enhancement of transcription factors binding to the promoter region of the TSG.

PMID- 27029828
TI  - Survival benefits of antiretroviral therapy in Brazil: a model-based analysis.
AB  - OBJECTIVE: In Brazil, universal provision of antiretroviral therapy (ART) has
      been guaranteed free of charge to eligible HIV-positive patients since December
      1996. We sought to quantify the survival benefits of ART attributable to this
      programme. METHODS: We used a previously published microsimulation model of HIV
      disease and treatment (CEPAC-International) and data from Brazil to estimate life
      expectancy increase for HIV-positive patients initiating ART in Brazil. We
      divided the period of 1997 to 2014 into six eras reflecting increased drug
      regimen efficacy, regimen availability and era-specific mean CD4 count at ART
      initiation. Patients were simulated first without ART and then with ART. The 2014
      censored and lifetime survival benefits attributable to ART in each era were
      calculated as the product of the number of patients initiating ART in a given era
      and the increase in life expectancy attributable to ART in that era. RESULTS: In
      total, we estimated that 598,741 individuals initiated ART. Projected life
      expectancy increased from 2.7, 3.3, 4.1, 4.9, 5.5 and 7.1 years without ART to
      11.0, 17.5, 20.7, 23.0, 25.3, and 27.0 years with ART in Eras 1 through 6,
      respectively. Of the total projected lifetime survival benefit of 9.3 million
      life-years, 16% (or 1.5 million life-years) has been realized as of December
      2014. CONCLUSIONS: Provision of ART through a national programme has led to
      dramatic survival benefits in Brazil, the majority of which are still to be
      realized. Improvements in initial and subsequent ART regimens and higher CD4
      counts at ART initiation have contributed to these increasing benefits.

PMID- 27029833
TI  - Decarboxylative Cross-Electrophile Coupling of N-Hydroxyphthalimide Esters with
      Aryl Iodides.
AB  - A new method for the decarboxylative coupling of alkyl N-hydroxyphthalimide
      esters (NHP esters) with aryl iodides is presented. In contrast to previous
      studies that form alkyl radicals from carboxylic acid derivatives, no
      photocatalyst, light, or arylmetal reagent is needed, only nickel and a reducing
      agent (Zn). Methyl, primary, and secondary alkyl groups can all be coupled in
      good yield (77% ave yield). One coupling with an acid chloride is also presented.
      Stoichiometric reactions of (dtbbpy)Ni(2-tolyl)I with an NHP ester show for the
      first time that arylnickel(II) complexes can directly react with NHP esters to
      form alkylated arenes. 

PMID- 27029834
TI  - Cell wall chemical characteristics of whole-crop cereal silages harvested at
      three maturity stages.
AB  - BACKGROUND: In cooler climates such as found in Scandinavian countries cereals
      are important feedstuffs for ruminants often ensiled as whole-crop cereal silages
      (WCCS) to preserve nutrients. Animal performance varies with the type of cereal
      forage and stage of cereal development being ensiled. Cell wall isolation and
      analysis was undertaken to determine differences among cereal silages harvested
      at different stages of maturity. RESULTS: A set of 27 WCCS samples of barley,
      wheat and oats harvested at heading, early milk, and dough stages of maturity
      were analyzed for cell wall (CW) composition and compared to previous NDF
      analyses. Total CW concentrations of the WCCS were higher than the NDF
      concentration. The lignin concentration was higher (P < 0.001) in oats (111 g kg(
      1) DM) than in barley (88 g kg(-1) DM) and wheat (91 g kg(-1) DM). Ferulates
      (ester and ether linked) ranged from 12.2 to 14.9 g kg(-1) across forage types
      and maturity stages. The correlation between total cell wall xylose and HC
      concentrations (NDF-ADF) was lower than expected in all forages (R = 0.63).
      CONCLUSION: The more comprehensive analyses of cell walls provide detailed
      composition of the different WCCS that vary due to the maturity and type of
      cereal. (c) 2016 The Authors. Journal of The Science of Food and Agriculture
      published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

PMID- 27029835
TI  - The field becomes the laboratory? The impact of the contextual digital footprint
      on the discipline of E/HF.
AB  - The increasing prevalence of affordable digital sensors, ubiquitous networking
      and computation puts us at what is only the start of a new era in terms of the
      volume, coverage and granularity of data that we can access about individuals and
      workplaces. This paper examines the consequences of harnessing this data deluge
      for the practice of E/HF. Focusing on what we term the 'contextual digital
      footprint', the trail of data we produce through interactions with many different
      digital systems over the course of even a single day, we describe three example
      scenarios (drawn from health care, distributed work and transportation) and
      examine how access to data directly drawn in considerable volume from the field
      will potentially change our application of design and evaluation methods. We
      conclude with a discussion of issues relevant to ethical and professional
      practice within this new environment including the increased challenges of
      respecting anonymity, working with n = all data-sets and the central role of
      ergonomists in promulgating positive uses of data while retaining a systems-based
      humanistic approach to work design. Practitioner summary: The paper envisions the
      impact of new and emerging sources of data about people and workplaces upon
      future practice in E/HF. We identify practical consequences for ergonomics
      practice, highlight new areas of professional competence likely to be required
      and flag both the risks and benefits of adopting a more data-driven approach.

PMID- 27029836
TI  - CENP-B box, a nucleotide motif involved in centromere formation, occurs in a New
      World monkey.
AB  - Centromere protein B (CENP-B) is one of the major proteins involved in centromere
      formation, binding to centromeric repetitive DNA by recognizing a 17 bp motif
      called the CENP-B box. Hominids (humans and great apes) carry large numbers of
      CENP-B boxes in alpha satellite DNA (AS, the major centromeric repetitive DNA of
      simian primates). Only negative results have been reported regarding the presence
      of the CENP-B box in other primate taxa. Consequently, it is widely believed that
      the CENP-B box is confined, within primates, to the hominids. We report here that
      the common marmoset, a New World monkey, contains an abundance of CENP-B boxes in
      its AS. First, in a long contig sequence we constructed and analysed, we
      identified the motif in 17 of the 38 alpha satellite repeat units. We then
      sequenced terminal regions of additional clones and found the motif in many of
      them. Immunostaining of marmoset cells demonstrated that CENP-B binds to DNA in
      the centromeric regions of chromosomes. Therefore, functional CENP-B boxes are
      not confined to hominids. Our results indicate that the efficiency of
      identification of the CENP-B box may depend largely on the sequencing methods
      used, and that the CENP-B box in centromeric repetitive DNA may be more common
      than researchers previously thought. 

PMID- 27029837
TI  - Temperature effects on virion volume and genome length in dsDNA viruses.
AB  - Heterogeneity in rates of survival, growth and reproduction among viruses is
      related to virus particle (i.e. virion) size, but we have little understanding of
      the factors that govern the four to five orders of magnitude in virus size
      variation. Here, we analyse variation in virion size in 67 double-stranded DNA
      viruses (i.e. dsDNA) that span all major biomes, and infect organisms ranging
      from single-celled prokaryotes to multicellular eukaryotes. We find that two
      metrics of virion size (i.e. virion volume and genome length) decrease by about
      55-fold as the temperature of occurrence increases from 0 to 40 degrees C. We
      also find that gene overlap increases exponentially with temperature, such that
      smaller viruses have proportionally greater gene overlap at higher temperatures.
      These results indicate dsDNA virus size increases with environmental temperature
      in much the same way as the cell or genome size of many host species. 

PMID- 27029838
TI  - Violence in the prehistoric period of Japan: the spatio-temporal pattern of
      skeletal evidence for violence in the Jomon period.
AB  - Whether man is predisposed to lethal violence, ranging from homicide to warfare,
      and how that may have impacted human evolution, are among the most controversial
      topics of debate on human evolution. Although recent studies on the evolution of
      warfare have been based on various archaeological and ethnographic data, they
      have reported mixed results: it is unclear whether or not warfare among
      prehistoric hunter-gatherers was common enough to be a component of human nature
      and a selective pressure for the evolution of human behaviour. This paper reports
      the mortality attributable to violence, and the spatio-temporal pattern of
      violence thus shown among ancient hunter-gatherers using skeletal evidence in
      prehistoric Japan (the Jomon period: 13 000 cal BC-800 cal BC). Our results
      suggest that the mortality due to violence was low and spatio-temporally highly
      restricted in the Jomon period, which implies that violence including warfare in
      prehistoric Japan was not common. 

PMID- 27029839
TI  - Migratory common blackbirds have lower innate immune function during autumn
      migration than resident conspecifics.
AB  - Animals need a well-functioning immune system to protect themselves against
      pathogens. The immune system, however, is costly and resource trade-offs with
      other demands exist. For migratory animals several (not mutually exclusive)
      hypotheses exist. First, migrants reduce immune function to be able to allocate
      resources to migration. Second, migrants boost immune function to cope with more
      and/or novel pathogens encountered during migration. Third, migrants reallocate
      resources within the immune system. We tested these hypotheses by comparing
      baseline immune function in resident and migratory common blackbirds (Turdus
      merula), both caught during the autumn migration season on the island of
      Helgoland, Germany. Indices of baseline innate immune function (microbial killing
      capacity and haptoglobin-like activity) were lower in migrants than in residents.
      There was no difference between the groups in total immunoglobulins, a measure of
      baseline acquired immune function. Our study on a short-distance avian migrant
      supports the hypothesis that innate immune function is compromised during
      migration. 

PMID- 27029840
TI  - Intrinsic temperature-dependent evolutions in the electron-boson spectral density
      obtained from optical data.
AB  - We investigate temperature smearing effects on the electron-boson spectral
      density function (I(2)chi(omega)) obtained from optical data using a maximum
      entropy inversion method. We start with two simple model input I(2)chi(omega),
      calculate the optical scattering rates at selected temperatures using the model
      input spectral density functions and a generalized Allen's formula, then extract
      back I(2)chi(omega) at each temperature from the calculated optical scattering
      rate using the maximum entropy method (MEM) which has been used for analysis of
      optical data of high-temperature superconductors including cuprates, and finally
      compare the resulting I(2)chi(omega) with the input ones. From this approach we
      find that the inversion process can recover the input I(2)chi(omega) almost
      perfectly when the quality of fits is good enough and also temperature smearing
      (or thermal broadening) effects appear in the I(2)chi(omega) when the quality of
      fits is not good enough. We found that the coupling constant and the
      logarithmically averaged frequency are robust to the temperature smearing effects
      and/or the quality of fits. We use these robust properties of the two quantities
      as criterions to check whether experimental data have intrinsic temperature
      dependent evolutions or not. We carefully apply the MEM to two material systems
      (one optimally doped and the other underdoped cuprates) and conclude that the
      I(2)chi(omega) extracted from the optical data contain intrinsic temperature
      dependent evolutions. 

PMID- 27029842
TI  - Effects of chitosan fiber addition on the properties of polyurethane with thermo
      responsive shape memory.
AB  - We investigated the effects of the addition of chitosan fiber (biomass nanofiber
      made by Sugino (BiNFi-s)) to polyether-based thermoplastic polyurethane (TPU) on
      material properties. BiNFi-s (2 and 5 wt %)/TPU composite materials were prepared
      via compression molding, and glass fiber (2 and 5 wt %)/TPU composite materials
      and plain TPU were also prepared for comparison. The glass transition temperature
      was analyzed using differential scanning calorimetry, and the crystal structure
      was investigated using X-ray diffraction. 20-mm-long test specimens with cross
      sectional dimensions of 1 mm * 1 mm were cut from sheets of the composite
      materials, and three-point bending tests were carried out using a universal
      testing machine to investigate their mechanical properties and shape memory. The
      addition of BiNFi-s or glass fiber to TPU did not influence the glass transition
      temperature, although the crystal structure changed from semi-crystalline to
      amorphous. The elastic modulus increased 40% by the addition of 5 wt % BiNFi-s
      (2.31 MPa) compared with plain TPU (1.65 MPa), and these composites exhibited
      shape recovery with clinically relevant changes in temperature. The addition of 5
      wt % BiNFi-s into TPU resulted in an improvement in the elastic modulus without
      any decrease in the shape memory effect. (c) 2016 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 105B: 1151-1156, 2017.

PMID- 27029841
TI  - Why we should consider sex (and study sex differences) in addiction research.
AB  - Among mammals, every cell has a biological sex, and the sex of an individual
      pervades its body and brain. In this review, we describe the processes through
      which mammals become phenotypically male or female by organizational and
      activational influences of genes and hormones throughout development. We
      emphasized that the molecular and cellular changes triggered by sex chromosomes
      and steroid hormones may generate sex differences in overt physiological
      functions and behavior, but they may alternatively promote end-point convergences
      between males and females. Clinical and pre-clinical evidences suggest that sex
      and gender differences modulate drug consumption as well as of the transition
      towards drug-promoted pathological states such as dependence and addiction.
      Additionally, sex differences in drug pharmacokinetics and pharmacodynamics will
      also influence dependence and addiction as well as side effects of drugs. These
      effects will further interact with socially gendered factors to result in sex
      differences in the access to, engagement in and efficacy of any therapeutic
      attempt. Finally, we maintain that 'sex sameness' is as important as 'sex
      differences' when building a complete understanding of biology for both males and
      females and provide a framework with which to classify and guide investigation
      into the mechanisms mediating sex differences and sex sameness.

PMID- 27029844
TI  - Obesity: a syndemics perspective.

PMID- 27029843
TI  - Graves' disease in a mediastinal mass presenting after total thyroidectomy for
      nontoxic multinodular goiter: a case report.
AB  - BACKGROUND: Thyrotoxicosis after total thyroidectomy is mostly iatrogenic.
      Rarely, a hyperfunctional thyroid remnant or ectopic tissue may be the cause.
      There are few cases of Graves' disease arising from thyroid tissue located in the
      mediastinum and none in which Graves' disease was diagnosed only after surgery.
      We report the case of a patient with Graves's disease in a mediastinal thyroid
      mass presenting 7 years after total thyroidectomy for nontoxic goiter. CASE
      PRESENTATION: A 67-year-old Caucasian woman presented with palpitations, fatigue
      and weight loss. She had a history of total thyroidectomy for nontoxic
      multinodular goiter at the age of 60 without any signs of malignancy on
      microscopic examination. She had been medicated with levothyroxine 100 MUg/day
      since the surgery without follow-up. She was tachycardic, had no cervical mass or
      eye involvement. Her thyroid-stimulating hormone levels were suppressed (0.000
      MUU/mL) and her free thyroxine (3.22 ng/dL) and free triiodothyronine (8.46
      pg/mL) levels increased. Neither mediastinal enlargement nor trachea deviation
      was found on chest roentgenogram. Levothyroxine treatment was stopped but our
      patient showed no improvement on free thyroxine or free triiodothyronine 10 days
      later. Thyroglobulin was increased to 294 mg/mL. A cervical ultrasound scan
      revealed no thyroid remnant. Her anti-thyroid-stimulating hormone receptor
      antibodies were high (19.7 U/L). Corporal scintigraphy demonstrated increased
      intrathoracic radioiodine uptake. A computed tomography scan confirmed a 60 * 40
      mm mediastinal mass. Methimazole 10 mg/day was started. Three months later, her
      thyroid function was normal and she underwent surgical resection. Microscopic
      examination showed thyroid tissue with no signs of malignancy. CONCLUSIONS:
      Although thyrotoxicosis after total thyroidectomy is mostly due to excessive
      supplementation, true hyperthyroidism may rarely be the cause, which should be
      kept in mind. The presence of thyroid tissue after total thyroidectomy in our
      patient may correspond to a remnant or ectopic thyroid tissue that became
      hyperfunctional in the presence of anti- thyroid-stimulating hormone receptor
      antibodies.

PMID- 27029845
TI  - Development of a G118R mutation in HIV-1 integrase following a switch to
      dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
AB  - OBJECTIVES: Dolutegravir shows a high barrier to resistance with no previously
      reported cases of acquired integrase mutations during first-line therapy. In this
      study, rapid development of the G118R mutation arose following a switch from
      first-line elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine to
      dolutegravir monotherapy. The G118R mutation also arose in a treatment
      experienced patient switched to dolutegravir monotherapy. The genetic basis for
      G118R selection and potential phenotypic outcome was ascertained. PATIENT AND
      METHODS: Genotypic analysis was performed on patients with virological failure
      (<1000 copies/mL) on dolutegravir-containing regimens. The Los Alamos database
      was queried for glycine codon 118 polymorphisms. Cell culture selections and
      phenotypic drug susceptibility assays assessed resistance via the G118R pathway.
      RESULTS: We report on two patients who developed viral failure while on
      dolutegravir monotherapy. Both patients had been on a current or previous regimen
      containing integrase inhibitors. Virological failure (<1000 copies/mL) emerged
      early within 2 months following the dolutegravir switch. The appearance of G118R
      in these two cases and subtype C and CRF02_AG in vitro selections were related to
      a rare GGA natural polymorphism at codon 118 (1.5% prevalence), facilitating a
      GGA to AGA transition. Cell culture selections were used to assess the in vitro
      progression of the G118R pathway leading to cross-resistance to all integrase
      inhibitors. CONCLUSIONS: Although resistance to dolutegravir is typically rare,
      genetic polymorphisms and monotherapy can facilitate the acquisition of G118R.

PMID- 27029847
TI  - Polyclonal spread of Streptococcus agalactiae resistant to clindamycin among
      pregnant women in Brazil.

PMID- 27029846
TI  - Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1
      infected individuals.
AB  - OBJECTIVES: Co-formulated elvitegravir, cobicistat, tenofovir disoproxil fumarate
      and emtricitabine is among the preferred regimens for first-line ART. A
      population approach was used to characterize the pharmacokinetics of elvitegravir
      and cobicistat and identify individual factors and co-medications influencing
      their disposition, taking into consideration the interaction between the two
      compounds. METHODS: The study population included 144 HIV-infected individuals
      who provided 186 and 167 elvitegravir and cobicistat plasma concentrations,
      respectively. First, distinct NONMEM((r)) analyses were conducted for
      elvitegravir and cobicistat, including individual demographic, clinical and
      genetic factors as potential covariates. Elvitegravir and cobicistat interaction
      was then assessed through different inhibitory models. Simulations based on the
      final model served to compare expected drug concentrations under standard and
      alternative dosage regimens. RESULTS: Clearance with between-subject variability
      was 7.6 L/h [coefficient of variation (CV) 16.6%] and volume of distribution 61 L
      for elvitegravir and 16.0 L/h (CV 41.9%) and 88.3 L, respectively, for
      cobicistat. Concomitant administration of non-ritonavir-boosted atazanavir
      decreased elvitegravir clearance by 35%, likely due to UDP-glucuronosyl
      transferase (UGT) 1A1 inhibition. Concomitant administration of non-ritonavir
      boosted atazanavir and ritonavir-boosted darunavir decreased cobicistat clearance
      by 47% and 27%, respectively. The final interaction model included cobicistat
      exposure (AUC0-24) on elvitegravir clearance. Simulations confirmed that a
      reduced elvitegravir dose of 85 mg co-administered with cobicistat and atazanavir
      produces a concentration-time course comparable to the standard regimen without
      atazanavir. CONCLUSIONS: Elvitegravir and cobicistat pharmacokinetic variability
      appears to be mainly explained by drug-drug interactions that may be encountered
      in routine clinical practice. In these cases, therapeutic drug monitoring and
      surveillance for potential toxicities would be justified.

PMID- 27029848
TI  - Activity of temocillin in a lethal murine model of infection of intra-abdominal
      origin due to KPC-producing Escherichia coli.
AB  - OBJECTIVES: Temocillin is a 6-alpha-methoxy derivative of ticarcillin that shows
      in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae
      carbapenemase (KPC). Our objective was to assess in vivo temocillin activity
      against KPC-producing Escherichia coli. METHODS: Isogenic derivatives of the WT
      E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental
      murine model of intra-abdominal infection with sepsis was used. Mice were treated
      subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the
      duration of time that the free serum concentration of temocillin exceeded the MIC
      in humans with a regimen of 2 g every 12 h or 2 g every 8 h. Blood, peritoneal
      fluid (PF) and spleen were collected; 24 h survival and sterility rates were
      assessed. RESULTS: Temocillin MICs were 8, 16, 32, and 256 mg/L for the
      susceptible strain and KPC-2-, KPC-3-, and OXA-48-producing strains,
      respectively. In mice treated with temocillin, significant bacterial reduction
      was obtained in PF, blood, and spleen for the susceptible strain and KPC-2- and
      KPC-3-producing strains (P < 0.001) but not for the OXA-48-producing strain.
      Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in
      blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%,
      57%, 0% (P < 0.001) for mice infected with the susceptible strain and KPC-2-, KPC
      3- and OXA-48-producing strains, respectively. CONCLUSIONS: In a lethal-infection
      model with bacteraemia from intra-abdominal origin, temocillin retained
      significant activity in PF, blood and spleen and prevented death in mice by
      effectively working against KPC-producing E. coli with temocillin MICs <=16 mg/L.

PMID- 27029849
TI  - Emerging plasmid-encoded colistin resistance: the animal world as the culprit?

PMID- 27029850
TI  - Comparative effects of overproducing the AraC-type transcriptional regulators
      MarA, SoxS, RarA and RamA on antimicrobial drug susceptibility in Klebsiella
      pneumoniae.
AB  - OBJECTIVES: In Klebsiella pneumoniae, overproduction of RamA and RarA leads to
      increased MICs of various antibiotics; MarA and SoxS are predicted to perform a
      similar function. We have compared the relative effects of overproducing these
      four AraC-type regulators on envelope permeability (a combination of outer
      membrane permeability and efflux), efflux pump and porin production, and
      antibiotic susceptibility in K. pneumoniae. METHODS: Regulators were overproduced
      using a pBAD expression vector. Antibiotic susceptibility was measured using disc
      testing. Envelope permeability was estimated using a fluorescent dye accumulation
      assay. Porin and efflux pump production was quantified using proteomics and
      validated using real-time quantitative RT-PCR. RESULTS: Envelope permeability and
      antibiotic disc inhibition zone diameters both reduced during overproduction of
      RamA and to a lesser extent RarA or SoxS, but did not change following
      overproduction of MarA. These effects were associated with overproduction of the
      efflux pumps AcrAB (for RamA and SoxS) and OqxAB (for RamA and RarA) and the
      outer membrane protein TolC (for all regulators). Effects on porin production
      were strain specific. CONCLUSIONS: RamA is the most potent regulator of
      antibiotic permeability in K. pneumoniae, followed by RarA then SoxS, with MarA
      having very little effect. This observed relative potency correlates well with
      the frequency at which these regulators are reportedly overproduced in clinical
      isolates.

PMID- 27029851
TI  - Intravenous amoxicillin/clavulanate for the prevention of bacteraemia following
      dental procedures: a randomized clinical trial.
AB  - OBJECTIVES: Although controversy exists regarding the efficacy of antibiotic
      prophylaxis for patients at risk of infective endocarditis, expert committees
      continue to publish recommendations for antibiotic prophylaxis regimens. This
      study aimed to evaluate the efficacy of four antimicrobial regimens for the
      prevention of bacteraemia following dental extractions. METHODS: The study
      population included 266 adults requiring dental extractions who were randomly
      assigned to the following five groups: control (no prophylaxis); 1000/200 mg of
      amoxicillin/clavulanate intravenously; 2 g of amoxicillin by mouth; 600 mg of
      clindamycin by mouth; and 600 mg of azithromycin by mouth. Venous blood samples
      were collected from each patient at baseline and at 30 s, 15 min and 1 h after
      dental extractions. Samples were inoculated into BACTEC Plus culture bottles and
      processed in the BACTEC 9240. Conventional microbiological techniques were used
      for subcultures and further identification of the isolated bacteria. The trial
      was registered at ClinicalTrials.gov with ID number NCT02115776. RESULTS: The
      incidence of bacteraemia in the control, amoxicillin/clavulanate, amoxicillin,
      clindamycin and azithromycin groups was: 96%, 0%, 50%, 87% and 81%, respectively,
      at 30 s; 65%, 0%, 10%, 65% and 49% at 15 min; and 18%, 0%, 4%, 19% and 18% at 1
      h. Streptococci were the most frequently identified bacteria. The percentage of
      positive blood cultures at 30 s post-extraction was lower in the
      amoxicillin/clavulanate group than in the amoxicillin group (P < 0.001). The
      incidence of bacteraemia in the clindamycin group was similar to that in the
      control group. CONCLUSIONS: Bacteraemia following dental extractions was
      undetectable with amoxicillin/clavulanate prophylaxis. Alternative antimicrobial
      regimens should be sought for patients allergic to the beta-lactams.

PMID- 27029852
TI  - Non-Hospitalized Patients with Mild Traumatic Brain Injury: The Forgotten
      Minority.
AB  - Non-hospitalized mild traumatic brain injury (mTBI) patients comprise a
      substantial part of the trauma population. For these patients, guidelines
      recommend specialized follow-up only in the case of persistent complaints or
      problems in returning to previous activities. This study describes injury and
      outcome characteristics of non-hospitalized mTBI patients, and the possibility of
      predicting which of the non-hospitalized patients will return to the outpatient
      neurology clinic. Data from all non-hospitalized mTBI patients (Glasgow Coma
      Scale [GCS] score 13-15, n = 462) from a prospective follow-up study on mTBI
      (UPFRONT-study) conducted in three level 1 trauma centers were analyzed. At 2
      weeks, and 3 and 6 months after injury, patients completed questionnaires on post
      traumatic complaints, depression, anxiety, outpatient follow-up, and resumption
      of activities. Most patients were male (57%), with a mean age of 40 years (range
      16-91 years). Injuries were most often caused by traffic accidents (32%) or falls
      (39%). Six months after injury, 36% showed incomplete recovery as defined by the
      Glasgow Outcome Scale - Extended (GOS-E). Twenty-five percent of the non
      hospitalized patients returned to the outpatient neurology clinic within 6 months
      after injury, of which one third had not completely resumed pre-injury
      activities. Regression analyses showed an increased risk for outpatient follow-up
      for patients scoring above the cutoff value for anxiety (odds ratio [OR] = 3.0),
      depression (OR = 3.5), or both (OR = 3.7) 2 weeks after injury. Our findings
      underline that clinicians and researchers should be aware of recovery for all
      mTBI patients, preventing their transition into a forgotten minority.

PMID- 27029853
TI  - Nabumetone use and risk of acute pancreatitis in a case-control study.
AB  - BACKGROUND: It remains unknown whether nabumetone increases or decreases acute
      pancreatitis risk. To investigate this, we conducted a population-based case
      control study using the database from the Taiwan National Health Insurance
      Program. METHODS: We analysed 5384 cases aged 20-84 years who had their first
      attack of acute pancreatitis during 1998-2011 and 21,536 controls without acute
      pancreatitis, and matched them according to sex, age and year in which acute
      pancreatitis was diagnosed. Never use of nabumetone was defined as subjects who
      had never received a nabumetone prescription; active use as subjects receiving a
      minimum of one prescription for nabumetone within 7 days before acute
      pancreatitis diagnosis and non-active use of nabumetone as subjects who did not
      receive a prescription for nabumetone within 7 days before but received at least
      one prescription for nabumetone >=8 days before. The odds ratio and 95%
      confidence interval (CI) were estimated to investigate the risk of acute
      pancreatitis associated with nabumetone use, using the multivariable
      unconditional logistic regression model. RESULTS: The adjusted odds ratio of
      acute pancreatitis was 3.69 (95%CI 1.69, 8.05) for subjects with active use of
      nabumetone compared with those with never use. The odds ratios decreased to 1.0
      (95%CI 0.88, 1.12) for subjects with non-active use. CONCLUSIONS: Active use of
      nabumetone may increase the risk of acute pancreatitis.

PMID- 27029854
TI  - Impact of presence and degree of pretreatment weight loss in locally-advanced
      pancreatic cancer patients treated with definitive concurrent chemoradiotherapy.
AB  - BACKGROUND: To assess the impact of the presence and degree of pretreatment
      weight loss (WL) on the survival of locally-advanced pancreas cancer (LAPC)
      patients treated with concurrent chemoradiotherapy (C-CRT). METHODS: Seventy
      three patients who received 50.4 Gy C-CRT were analyzed. All patients underwent
      laparoscopy (n = 18) or laparotomy (n = 55), and biopsies were obtained for
      histologic examination of the primary tumor and enlarged/metabolically active
      regional lymph nodes. Pretreatment WL and percentage WL (PWL) were calculated by
      utilizing data obtained 6 months prior to and during hospital admission. The
      primary objective was to assess the influence WL status on overall survival (OS),
      and the secondary objective was the identification of a PWL cut-off value, if
      available. RESULTS: Forty-five (61.6%) patients had WL. Median OS was 14.4 months
      for the entire study population which was significantly longer in the non-WL than
      the WL cohort (21.4 vs. 11.3 months; p < 0.003). On further analysis a cut-off
      value of 3.1% was identified for WL. Accordingly, patients with WL < 3.1% had
      significantly longer OS than those with WL >= 3.1% (25.8 vs. 10.1 months; p <
      0.001). In multivariate analysis, both the WL status (p < 0.001) and PWL (p =
      0.002) retained their independent significance. CONCLUSION: Both the presence and
      degree of WL prior to C-CRT had strong adverse effects on the survival of LAPC
      patients, even if they presented with a BMI > 20 kg/m(2). Additionally, a WL of
      >=3.1% in the last 6 months appeared to be a strong cut-off for the
      stratification of such patients into distinctive survival groups.

PMID- 27029855
TI  - Haemophilia neonates: mode of delivery and perinatal complications.

PMID- 27029856
TI  - Identification of plant vacuolar transporters mediating phosphate storage.
AB  - Plant vacuoles serve as the primary intracellular compartments for inorganic
      phosphate (Pi) storage. Passage of Pi across vacuolar membranes plays a critical
      role in buffering the cytoplasmic Pi level against fluctuations of external Pi
      and metabolic activities. Here we demonstrate that the SPX-MFS proteins,
      designated as PHOSPHATE TRANSPORTER 5 family (PHT5), also named Vacuolar
      Phosphate Transporter (VPT), function as vacuolar Pi transporters. Based on (31)P
      magnetic resonance spectroscopy analysis, Arabidopsis pht5;1 loss-of-function
      mutants accumulate less Pi and exhibit a lower vacuolar-to-cytoplasmic Pi ratio
      than controls. Conversely, overexpression of PHT5 leads to massive Pi
      sequestration into vacuoles and altered regulation of Pi starvation-responsive
      genes. Furthermore, we show that heterologous expression of the rice homologue
      OsSPX-MFS1 mediates Pi influx to yeast vacuoles. Our findings show that a group
      of Pi transporters in vacuolar membranes regulate cytoplasmic Pi homeostasis and
      are required for fitness and plant growth. 

PMID- 27029857
TI  - Validation of a rapid type 1 diabetes autoantibody screening assay for community
      based screening of organ donors to identify subjects at increased risk for the
      disease.
AB  - The Network for Pancreatic Organ donors with Diabetes (nPOD) programme was
      developed in response to an unmet research need for human pancreatic tissue
      obtained from individuals with type 1 diabetes mellitus and people at increased
      risk [i.e. autoantibody (AAb)-positive] for the disease. This necessitated the
      establishment of a type 1 diabetes-specific AAb screening platform for organ
      procurement organizations (OPOs). Assay protocols for commercially available
      enzyme-linked immunosorbent assays (elisas) determining AAb against glutamic acid
      decarboxylase (GADA), insulinoma-associated protein-2 (IA-2A) and zinc
      transporter-8 (ZnT8A) were modified to identify AAb-positive donors within strict
      time requirements associated with organ donation programmes. These rapid elisas
      were evaluated by the international islet AAb standardization programme (IASP)
      and used by OPO laboratories as an adjunct to routine serological tests
      evaluating donors for organ transplantation. The rapid elisas performed well in
      three IASPs (2011, 2013, 2015) with 98-100% specificity for all three assays,
      including sensitivities of 64-82% (GADA), 60-64% (IA-2A) and 62-68% (ZnT8A).
      Since 2009, nPOD has screened 4442 organ donors by rapid elisa; 250 (5.6%) were
      identified as positive for one AAb and 14 (0.3%) for multiple AAb with 20 of
      these cases received by nPOD for follow-up studies (14 GADA+, two IA-2A(+) , four
      multiple AAb-positive). Rapid screening for type 1 diabetes-associated AAb in
      organ donors is feasible, allowing for identification of non-diabetic, high-risk
      individuals and procurement of valuable tissues for natural history studies of
      this disease. 

PMID- 27029858
TI  - A new insight into high-strength Ti62Nb12.2Fe13.6Co6.4Al5.8 alloys with bimodal
      microstructure fabricated by semi-solid sintering.
AB  - It is well known that semi-solid forming could only obtain coarse-grained
      microstructure in a few alloy systems with a low melting point, such as aluminum
      and magnesium alloys. This work presents that semi-solid forming could also
      produce novel bimodal microstructure composed of nanostructured matrix and micro
      sized (CoFe)Ti2 twins in a titanium alloy, Ti62Nb12.2Fe13.6Co6.4Al5.8. The semi
      solid sintering induced by eutectic transformation to form a bimodal
      microstructure in Ti62Nb12.2Fe13.6Co6.4Al5.8 alloy is a fundamentally different
      approach from other known methods. The fabricated alloy exhibits high yield
      strength of 1790 MPa and plastic strain of 15.5%. The novel idea provides a new
      insight into obtaining nano-grain or bimodal microstructure in alloy systems with
      high melting point by semi-solid forming and into fabricating high-performance
      metallic alloys in structural applications. 

PMID- 27029860
TI  - Corrigendum.

PMID- 27029859
TI  - Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the
      Baltimore Longitudinal Study of Aging.
AB  - Aging is characterized by progressive decline in muscle mass, strength, and
      quality all of which contribute to functional impairment, falls, mobility
      disability, and frailty. Circulating factors may provide clues on the mechanisms
      for decline in muscle quality with aging. Characterizing the metabolic profile
      associated with reduced muscle quality in older persons could have important
      translational implications for the early identification of subjects at high risk
      of developing sarcopenia and the identification of targets for new preventive
      strategies and treatments. In a pilot cross-sectional, case-control study nested
      in the Baltimore Longitudinal Study on Aging, we compared circulating metabolites
      between 79 participants with low muscle quality ratio and 79 controls with high
      muscle quality, matched by age, sex, and height. The concentrations of 180
      metabolites were determined by LC MS/MS, using the Biocrates p180 system, a
      targeted metabolomics approach. Participants with low muscle quality had
      significantly higher levels of leucine, isoleucine, tryptophan, serotonin, and
      methionine, while those with high muscle quality had significantly lower levels
      of putrescine and the selected phophatidylcholine (PCs) and lysoPCs. The results
      of this study open a new road for future investigations aimed at identifying new
      metabolic pathways involved in the decline of muscle quality with aging.

PMID- 27029861
TI  - Obituary: Professor Ying-Xiang Wang (1938-2016).

PMID- 27029862
TI  - In Memory of Professor Ying-Xiang WANG.

PMID- 27029863
TI  - Influences of local habitat, tributary position, and dam characteristics on fish
      assemblages within impoundments of low-head dams in the tributaries of the Qingyi
      River, China.
AB  - Low-head dam impoundments modify local habitat and alter fish assemblages;
      however, to our knowledge, the pattern of how fish assemblages in the
      impoundments relate to local habitat, tributary position, and dam characteristics
      is still unclear. We used data collected in 62 impoundments created by low-head
      dams in headwater streams of the Qingyi River, China, to examine relationships
      between fish assemblages and local habitat, tributary position, and dam
      characteristics. We also assessed the relative importance of the three groups of
      factors in determining fish species richness and composition. Linear regression
      models showed that fish species richness was related to substrate heterogeneity,
      confluence link, and dam number upstream. Redundancy analysis showed that fish
      species compositions were influenced by substrate heterogeneity, confluence link,
      dam height, dam numbers upstream and downstream. Overall, dam characteristics
      were more important in affecting fish species richness but less important in
      determining fish species composition than local habitat (i.e., substrate
      heterogeneity) and tributary position. Our results suggest that low-head dam may
      affect fish species richness in impoundments by modifying local habitat and
      constraining fish movement, and the relative abundances of those fish species may
      depend more on species habitat presences and stream size than on impoundment size
      and number.

PMID- 27029864
TI  - Short photoperiod increases energy intake, metabolic thermogenesis and organ mass
      in silky starlings Sturnus sericeus.
AB  - Environmental cues play important roles in the regulation of an animal's
      physiology and behavior. One such cue, photoperiod, plays an important role in
      the seasonal acclimatization of birds. It has been demonstrated that an animal's
      body mass, basal metabolic rate (BMR), and energy intake, are all affected by
      photoperiod. The present study was designed to examine photoperiod induced
      changes in the body mass, metabolism and metabolic organs of the silky starling,
      Sturnus sericeus. Captive silky starlings increased their body mass and BMR
      during four weeks of acclimation to a short photoperiod. Birds acclimated to a
      short photoperiod also increased the mass of certain organs (liver, gizzard and
      small intestine), and both gross energy intake (GEI) and digestible energy intake
      (DEI), relative to those acclimated to a long photoperiod. Furthermore, BMR was
      positively correlated with body mass, liver mass, GEI and DEI. These results
      suggest that silky starlings increase metabolic thermogenesis when exposed to a
      short photoperiod by increasing their body and metabolic organ mass, and their
      GEI and DEI. These findings support the hypothesis that bird species from
      temperate climates typically display high phenotypic flexibility in thermogenic
      capacity.

PMID- 27029865
TI  - Diurnal brooding behavior of long-tailed tits (Aegithalos caudatus
      glaucogularis).
AB  - Brooding is a major breeding investment of parental birds during the early
      nestling stage, and has important effects on the development and survival of
      nestlings. Investigating brooding behavior can help to understand avian breeding
      investment strategies. From January to June in 2013 and 2014, we studied the
      brooding behaviors of long-tailed tits (Aegithalos caudatus glaucogularis) in
      Dongzhai National Nature Reserve, Henan Province, China. We analyzed the
      relationships between parental diurnal brooding duration and nestling age, brood
      size, temperature, relative breeding season, time of day and nestling frequencies
      during brooding duration. Results showed that female and male long-tailed tit
      parents had different breeding investment strategies during the early nestling
      stage. Female parents bore most of the brooding investment, while male parents
      performed most of the nestling feedings. In addition, helpers were not found to
      brood nestlings at the two cooperative breeding nests. Parental brooding duration
      was significantly associated with the food delivered to nestlings (F=86.10, df=1,
      193.94, P<0.001), and was longer when the nestlings received more food. We found
      that parental brooding duration declined significantly as nestlings aged (F=5.99,
      df=1, 50.13, P=0.018). When nestlings were six days old, daytime parental
      brooding almost ceased, implying that longtailed tit nestlings might be able to
      maintain their own body temperature by this age. In addition, brooding duration
      was affected by both brood size (F=12.74, df=1, 32.08, P=0.001) and temperature
      (F=5.83, df=1, 39.59, P=0.021), with it being shorter in larger broods and when
      ambient temperature was higher.

PMID- 27029866
TI  - Effects of osmotic pressure, temperature and stocking density on survival and
      sexual reproduction of Craspedacusta sowerbii.
AB  - The effects of osmotic pressure, temperature and stocking density on medusae
      survival of Craspedacusta sowerbii were examined. The medusae were shown to be
      sensitive to the variations of osmotic pressure. And the survival time was <90 h
      at 34 mOsm/L and it declined rapidly with rising osmotic pressure. The peak
      survival time of >200 h was recorded at 0.2 mOsm/L. Comparing with 27C and 32C
      treatments, 23C treatment yielded lower activities at a range of 8-13/min.
      However, there was a longer survival time. A non-linear relationship existed
      between survival time and stocking density. Lower density resulted in larger body
      size. And sexual reproduction resumed after breeding for >22 days. Newly-formed
      polyps and medusae appeared subsequently but only in the higher-density groups of
      10, 14 and 18 ind./L. It suggested that the number of newly-formed polyps and
      medusae was highly dependent on stocking density. That is, a higher stocking
      density produced more organisms. However, newly-formed medusae died within one
      month and none grew a diameter of >5 mm.

PMID- 27029867
TI  - Molecular cloning, pathologically-correlated expression and functional
      characterization of the colonystimulating factor 1 receptor (CSF-1R) gene from a
      teleost, Plecoglossus altivelis.
AB  - Colony-stimulating factor 1 receptor (CSF-1R) is an important regulator of
      monocytes/macrophages (MO/MPhi). Although several CSF-1R genes have been
      identified in teleosts, the precise role of CSF- 1R in ayu (Plecoglossus
      altivelis) remains unclear. In this study, we characterized the CSF-1R homologue
      from P. altivelis, and named it PaCSF-1R. Multiple sequence alignment and
      phylogenetic tree analysis showed that PaCSF-1R was most closely related to that
      of Japanese ricefish (Oryzias latipes). Tissue distribution and expression
      analysis showed that the PaCSF-1R transcript was mainly expressed in the head
      kidney-derived MO/MPhi, spleen, and head kidney, and its expression was
      significantly altered in various tissues upon Vibrio anguillarum infection. After
      PaCSF-1R neutralization for 48 h, the phagocytic activity of MO/MPhi was
      significantly decreased, suggesting that PaCSF-1R plays a role in regulating the
      phagocytic function of ayu MO/MPhi.

PMID- 27029868
TI  - Huangshan population of Chinese Zacco platypus (Teleostei, Cyprinidae) harbors
      diverse matrilines and high genetic diversity.
AB  - Six main mitochondrial DNA (mtDNA) lineages have been described in minnow (Zacco
      platypus) samples obtained from northern, western and southern China. Perdices et
      al. (2004) predicted that further sampling of other tributaries might discover
      more lineages of this species. In this study, we collected 26 Zacco platypus
      individuals in the Huangshan area of eastern China and determined the cytochrome
      b (cytb) sequence variations. Combined with reported data in GenBank, we
      identified ten matrilines (Zacco A-J) in a total of 169 samples, with relatively
      high molecular divergence found among them. The Huangshan population had the
      greatest genetic variation among all sampled regions and hosted six of the ten
      matrilines. Our results highlight the significance of the Huangshan area for the
      conservation of Zacco platypus.

PMID- 27029870
TI  - Journal Correction.

PMID- 27029869
TI  - ZIKA--How fast does this virus mutate?
AB  - The World Health Organization has declared the present Zika virus epidemic to be
      a 'Public Health Emergency of International Concern'. The virus appears to have
      spread from Thailand to French Polynesia in 2013, and has since infected over a
      million people in the countries of South and Central America. In most cases the
      infection is mild and transient, but the virus does appear to be strongly
      neurotropic and the presumptive cause of both birth defects in fetuses and
      Guillain-Barre syndrome in some adults. In this paper, the techniques and
      utilities developed in the study of mitochondrial DNA were applied to the Zika
      virus. As a result, it is possible to show in a simple manner how a phylogenetic
      tree may be constructed and how the mutation rate of the virus can be measured.
      The study showed the mutation rate to vary between 12 and 25 bases a year, in a
      viral genome of 10272 bases. This rapid mutation rate will enable the geographic
      spread of the epidemic to be monitored easily and may also prove useful in
      assisting the identification of preventative measures that are working, and those
      that are not.

PMID- 27029871
TI  - Microarray-based IgE serology improves management of severe atopic dermatitis in
      two children.

PMID- 27029872
TI  - Couples at risk from exposure to Zika virus should consider delaying pregnancy,
      says CDC.

PMID- 27029873
TI  - [The DANAMI-3-PRIMULTI study].

PMID- 27029874
TI  - [Physical activity and cardiovascular health].
AB  - It is well known that regular moderate physical activity, in the context of a
      healthy lifestyle, significantly reduces the likelihood of cardiovascular events,
      both in primary and secondary prevention. In addition, it is scientifically
      proven that exercise can reduce the incidence of diabetes, osteoporosis,
      depression, breast cancer and colon cancer. Despite this strong evidence,
      sedentary lifestyle remains a widespread habit in the western world. Even in
      Italy the adult population has a poor attitude to regular physical activity. It
      is therefore necessary, as continuously recommended by the World Health
      Organization, to motivate people to "move" since the transition from inactivity
      to regular light to moderate physical activity has a huge impact on health,
      resulting in significant savings of resources. We do not need to be athletes to
      exercise - it should be part of all our daily routines. 

PMID- 27029875
TI  - [The root of the deep and fast ongoing evolution of both structure and
      methodology of clinical research].
AB  - The growing scientific knowledge and technology development are leading to
      radical changes in biological and medical research. The prevalent lines of
      development deal with a pragmatic evolution of controlled clinical trials, a
      massive diffusion of observational research, which is progressively incorporated
      in clinical practice, new models and designs of clinical research, the systematic
      use of information technology to build up vast networks of medical centers
      producing huge amounts of shared data to be managed through the big data
      methodology, personalized as well as precision medicine, a reshaped physician
      patient relationship based on a co-working principle. All this is leading to
      profound changes in public health governance, a renewal of clinical epidemiology
      and prevention, a modified structure of several specific sectors of medical care,
      hopefully guided by scientific evidences. A few aspects of such an evolving
      picture are discussed in this article. 

PMID- 27029876
TI  - [Will big data satisfy the unmet needs of clinical research?].

PMID- 27029877
TI  - [Molecular targets and novel pharmacological options to prevent myocardial
      hypertrophic remodeling].
AB  - Myocardial hypertrophic remodeling is a pathophysiological feature of several
      cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the
      most common monogenic inherited disease of the heart. In recent years,
      preclinical and clinical studies investigated the underlying molecular mechanisms
      and intracellular signaling pathways involved in pathologic cardiomyocyte
      hypertrophy and highlighted a number of possible molecular targets of therapy
      aimed at preventing its development. Early prevention of myocardial hypertrophic
      remodeling is particularly sought after in HCM, as current therapeutic strategies
      are unable to remove the primary cause of disease, i.e. the disease-causing gene
      mutation. Studies on transgenic animal models or human myocardial samples from
      patients with HCM identified intracellular calcium overload as a central
      mechanism driving pathological hypertrophy. In this review, we analyze recent
      preclinical and clinical studies on animal models and patients with HCM aimed at
      preventing or modifying hypertrophic myocardial remodeling. Mounting evidence
      shows that prevention of pathological hypertrophy is a feasible strategy in HCM
      and will enter the clinical practice in the near future. Considering the close
      mechanistic similarities between HCM and secondary hypertrophy, these studies are
      also relevant for the common forms of cardiac hypertrophy, such as hypertensive
      or valvular heart disease. 

PMID- 27029878
TI  - [Work-up and management of constrictive pericarditis: a critical review].
AB  - Constrictive pericarditis is a rare pericardial disorder that causes an
      impairment of cardiac filling and frequently heart failure. The clinical
      presentation is non-specific and the differential diagnosis includes myocardial
      diseases, particularly restrictive cardiomyopathy. Echocardiography has a central
      role in the initial diagnosis. Some peculiar signs, such as abnormal inspiratory
      shift of the interventricular septum, increased respiratory variations of
      transmitral, transtricuspid and hepatic vein flow velocities and the normality of
      early diastolic relaxation velocity (e') at tissue Doppler, increase the
      likelihood of the disease. These signs are an expression of increased ventricular
      interdependence and dissociation between intrathoracic and intracardiac pressures
      typical of pericardial constriction. For further diagnosis, computed tomography
      and magnetic resonance are used to identify the presence of pericardial
      thickening. Invasive cardiac catheterization is indicated in dubious cases and in
      the assessment of the severity of hemodynamic abnormalities, especially in cases
      with surgical indication. Pericardiectomy is indicated in symptomatic patients
      meeting the diagnostic criteria of constrictive pericarditis and is able to
      improve the prognosis. 

PMID- 27029879
TI  - [Heart transplant: when the candidate is a child].
AB  - Heart transplant (HT) has been considered as a therapy for pediatric end-stage
      heart failure (HF) for more than four decades. Children with HF represent a very
      heterogeneous population, affected by different congenital or acquired heart
      diseases. Progresses in cardiac surgery and medical therapies, leading to
      improved prognosis, require periodic re-assessment of indications to HT. Systemic
      diseases, inherited inborn errors of metabolism, genetic syndromes or associated
      extra-cardiac malformations can contraindicate HT. In these conditions a tailored
      evaluation is needed. Pediatric heart disease, which more often may be an
      indication to HT, as well as prognostic parameters in pediatric HF are discussed.

PMID- 27029880
TI  - [The Italian Survey on Cardiac Rehabilitation - 2013 (ISYDE.13-Directory):
      national availability and organization of cardiac rehabilitation facilities].
AB  - BACKGROUND: The Italian Association for Cardiovascular Prevention, Rehabilitation
      and Epidemiology (GICR-IACPR) and the Italian Society of Cardiologists of
      Accredited Hospitals (SICOA) developed the ISYDE.13 survey with the purpose to
      take a detailed snapshot of number, distribution, facilities, staffing levels,
      organization, and program details of cardiac rehabilitation (CR) units in Italy.
      METHODS: The study was carried out using a web-based questionnaire running on the
      GICR-IACPR website for 4 weeks from September 2 to 29, 2013. RESULTS: Out of 221
      CR centers existing in Italy (+14% vs 2008), 191 (86%) participated in the
      survey. On a national basis, there is a CR unit every 268 852 inhabitants. The
      majority of CR units are located in public hospitals (57.1%), the remaining 42.9%
      in private hospitals; 130 CR centers (68%) provide inpatients care and account
      for 3527 beds (5.9 per 100 000 inhabitants): of these 374 are day-hospital beds
      and 408 are sub-intensive beds. Forty-one of the Italian in-hospital CR centers
      offer also outpatient programs and 61 centers (32%) offer only outpatient CR
      programs; 131 of the CR units (68.6%) are linked to dedicated cardiology
      divisions and in 77% of cases the head is a cardiologist. Home-based programs are
      offered by 9 centers (4.7%) and CR programs with telecare supervision by 16
      (8.4%). Long-term secondary prevention follow-up programs are provided by 94 of
      CR services (49.2%). During one week of activity, the 191 centers completed 1335
      inpatient CR programs and 971 outpatient CR programs. According to these data, it
      may be assumed that in Italy approximately 100 000 patients are referred annually
      to CR programs. CONCLUSIONS: ISYDE.13 showed an incremental trend of CR provision
      in Italy, particularly in outpatient programs. However, at present, the national
      network of CR units covers only one third of the potential requirements defined
      by current secondary prevention recommendations.

PMID- 27029881
TI  - [Preliminary results and future perspectives of the Piedmont Adult Congenital
      Heart Disease Registry].
AB  - BACKGROUND: Adults with congenital heart disease are a relatively new population
      that progressively increases in size and complexity. In Italy, there are no
      accurate data concerning the distribution of congenital defects and the long-term
      outcome relating to both congenital heart disease per se and comorbidities, due
      to the aging process. METHODS: The Piedmont Adult Congenital Heart Disease
      Registry has been designed to investigate these aspects and to support a high
      quality healthcare development for grown-up congenital heart patients. Within 2
      years, 459 consecutive patients routinely followed in 10 divisions of cardiology
      in Piedmont were included in the project. Electronic dedicated software has
      supported data collection. RESULTS: Mean age of patients is 35 +/- 16 years.
      Septal defects are the most common type of congenital heart disease (35.3%). At
      baseline evaluation, 71.7% of patients reported a previous surgical and/or
      percutaneous treatment and 6.3% an electrophysiological procedure. Freedom from
      intervention is 44%, 81% and 56% at the age of 18, 30 and 45 years, respectively.
      Patients who had a treatment during infancy show a better intervention-free
      survival (p=0.038) compared with patients treated during adulthood. Despite the
      majority of the population had an almost preserved functional status, 27.5% had
      >=1 long-term sequelae (arrhythmias 27.5%; pulmonary hypertension 5.2%;
      neurological problems 4.1%; cyanosis 4.8%; liver dysfunction 2.4%; enteropathy
      2.4%; lung disease 2.2%). During 2 years of follow-up, the estimated mortality
      rate is 0.88%. CONCLUSIONS: Adults with congenital heart disease are a
      heterogeneous population of relatively young patients with relevant clinical and
      social problems. The late sequelae related to both the underlying heart disease
      and the advancing age require continuous monitoring and lifelong specialized
      care.

PMID- 27029882
TI  - [Molecular biology as a diagnostic tool in the newborn Emergency department: a
      rare case of idiopathic infantile arterial calcification].
AB  - A Turkish female infant of 96 days was admitted to the pediatric emergency room
      because of inconsolable crying, persistent cough, and difficulty in feeding
      during the previous day. She was conscious and did not show any signs or symptoms
      of multiorgan failure. A few minutes afterwards, the child experienced cardiac
      arrest with an initial cardiac rhythm of asystole and died 75 minutes later
      following cardiopulmonary resuscitation maneuvers. As the pathological cause of
      death, autopsy findings revealed a rare type of idiopathic infantile arterial
      calcification resulting from a mutation in the gene encoding for the ENPP1
      enzyme. 

PMID- 27029883
TI  - [Late structural discontinuity and migration of a bioabsorbable scaffold in a
      saphenous vein graft].
AB  - The use of bioresorbable vascular scaffolds (BVS) has many important and
      potentially useful features, on both pathophysiological and clinical grounds, for
      the treatment of native coronary artery stenosis. These advantages are less well
      established when BVS are employed in saphenous vein graft disease. We here
      describe a peculiar behavior of a previously (6 months) implanted BVS in a
      degenerated saphenous vein graft during treatment of an in-stent restenosis in a
      patient suffering from unstable angina. This BVS particular performance seems to
      suggest that different pathophysiological and anatomical conditions may play a
      relevant role in affecting the results of transluminal vascular therapy. 

PMID- 27029884
TI  - [Pulmonary embolism in complex corrected congenital heart disease].
AB  - Pulmonary embolism is an uncommon but potentially fatal disease in children,
      especially with congenital heart disease where pulmonary perfusion depends on
      caval flow. Anticoagulation is the mainstay of therapy for children with
      pulmonary embolism. However, thrombolytic therapy can also be considered. The
      outcome of pediatric pulmonary embolism is uncertain and needs further
      investigation. We suggest increased awareness and a high index of suspicion in
      the presence of suggestive clinical signs in high-risk patients in order to
      initiate prompt diagnostic imaging and treatment. 

PMID- 27029886
TI  - Orbitally induced hierarchy of exchange interactions in the zigzag
      antiferromagnetic state of honeycomb silver delafossite Ag3Co2SbO6.
AB  - We report the revised crystal structure, static and dynamic magnetic properties
      of quasi-two dimensional honeycomb-lattice silver delafossite Ag3Co2SbO6. The
      magnetic susceptibility and specific heat data are consistent with the onset of
      antiferromagnetic long range order at low temperatures with Neel temperature TN ~
      21.2 K. In addition, the magnetization curves revealed a field-induced (spin-flop
      type) transition below TN in moderate magnetic fields. The GGA+U calculations
      show the importance of the orbital degrees of freedom, which maintain a hierarchy
      of exchange interaction in the system. The strongest antiferromagnetic exchange
      coupling was found in the shortest Co-Co pairs and is due to direct and
      superexchange interaction between the half-filled xz + yz orbitals pointing
      directly to each other. The other four out of six nearest neighbor exchanges
      within the cobalt hexagon are suppressed, since for these bonds the active half
      filled orbitals turned out to be parallel and do not overlap. The electron spin
      resonance (ESR) spectra reveal a broad absorption line attributed to the Co(2+)
      ion in an octahedral coordination with an average effective g-factor g = 2.40 +/-
      0.05 at room temperature and show strong divergence of the ESR parameters below
      ~150 K, which implies an extended region of short-range correlations. Based on
      the results of magnetic and thermodynamic studies in applied fields, we propose a
      magnetic phase diagram for the new honeycomb-lattice delafossite.

PMID- 27029888
TI  - Antiretroviral pre-exposure prophylaxis for HIV prevention is highly effective in
      community settings.

PMID- 27029887
TI  - Structural determinants governing S100A4-induced isoform-selective disassembly of
      nonmuscle myosin II filaments.
AB  - The Ca(2+) -binding protein S100A4 interacts with the C terminus of nonmuscle
      myosin IIA (NMIIA) causing filament disassembly, which is correlated with an
      increased metastatic potential of tumor cells. Despite high sequence similarity
      of the three NMII isoforms, S100A4 discriminates against binding to NMIIB. We
      searched for structural determinants of this selectivity. Based on paralog
      scanning using phage display, we identified a single position as major
      determinant of isoform selectivity. Reciprocal single amino acid replacements
      showed that at position 1907 (NMIIA numbering), the NMIIA/NMIIC-specific alanine
      provides about 60-fold higher affinity than the NMIIB-specific asparagine. The
      structural background of this can be explained in part by a communication between
      the two consecutive alpha-helical binding segments. This communication is
      completely abolished by the Ala-to-Asn substitution. Mutual swapping of the
      disordered tailpieces only slightly affects the affinity of the NMII chimeras.
      Interestingly, we found that the tailpiece and position 1907 act in a nonadditive
      fashion. Finally, we also found that the higher stability of the C-terminal
      coiled-coil region of NMIIB also discriminates against interaction with S100A4.
      Our results clearly show that the isoform-selective binding of S100A4 is
      determined at multiple levels in the structure of the three NMII isoforms and the
      corresponding functional elements of NMII act synergistically with one another
      resulting in a complex interaction network. The experimental and in silico
      results suggest two divergent evolutionary pathways: NMIIA and NMIIB evolved to
      possess S100A4-dependent and -independent regulations, respectively.

PMID- 27029889
TI  - The volume of the carotid bodies and blood pressure variability and pulse
      pressure in patients with essential hypertension.
AB  - AIM: To assess the relationship between the volume of the carotid bodies
      (VrCB+lCB) examined by means of computed tomography angiography (CTA) and blood
      pressure variability and pulse pressure (PP) in 24-hour ambulatory blood pressure
      monitoring (ABPM) in patients with essential hypertension. MATERIALS AND METHODS:
      A group of 52 patients with essential hypertension was examined (mean age:
      68.32+/-12.31 years), the sizes of carotid bodies were measured by means of
      carotid artery CTA, and 24-hour ABPM was carried out. The 24-hour ABPM
      established systolic blood pressure (SBP), diastolic blood pressure (DBP), mean
      arterial pressure (MAP), PP, SBP variability (SBPV), and DBP variability (DBPV).
      RESULTS: SBP, MAP, and SBPV were significantly higher in the group of
      hypertension patients with VrCB+lCB equal to or above the median than in the
      group of hypertension patients with VrCB+lCB less than the median, as well as in
      the group of hypertension patients with oversized carotid bodies, than in the
      group of hypertension patients with normal VrCB+lCB. Moreover, the PP was
      statistically significantly higher in the group of hypertension patients with
      VrCB+lCB equal to or above the median than in the group of hypertension patients
      with VrCB+lCB less than the median. The existence of statistically significant
      positive linear relationships was revealed between VrCB+lCB and SBP, PP, and
      SBPV. A higher body mass index, older age, smoking, and higher VrCB+lCB are
      independent risk factors increasing SBPV in the research group. CONCLUSION: A
      positive relationship between the size of the carotid bodies and variability of
      the SBP and PP is observed in patients with essential hypertension.

PMID- 27029890
TI  - Reintervention for occluded metal stent in malignant bile duct obstruction: A
      prospective randomized trial comparing covered and uncovered metal stent.
AB  - BACKGROUND AND AIM: No prospective data are available on comparing covered and
      uncovered self-expandable metal stent (SEMS) for reintervention of occluded
      uncovered metal stents during endoscopic retrograde cholangiopancreatography in
      patients with malignant distal biliary obstruction. METHODS: From June 2010 to
      November 2014, 43 patients with inoperable distal biliary obstruction of a
      previously placed uncovered SEMS were enrolled from three centers in Korea and
      randomly assigned to covered (n = 22) or uncovered SEMS group (n = 21). The
      primary outcome was overall stent patency. Secondary outcome was time-to-stent
      occlusion, patient survival, cause of stent occlusion, and adverse events.
      RESULTS: Overall median patency of secondary stent was 112.0 days. Median stent
      patency of covered and uncovered SEMS was 112.0 and 181.0 days, respectively, (P
      = 0.373). There was a tendency towards a longer time-to-stent occlusion in
      uncovered SEMS group (median: 112.0 vs 181.0 days). However, it did not reach
      statistical significance (P = 0.214). Most common causes of occlusion were stent
      clogging (36.4%) and tumor ingrowth (33.3%) in covered and uncovered SEMS groups,
      respectively. There was no significant difference in median survival between the
      groups (median: 308 vs 300 days; P = 0.325). Acute cholangitis occurred in four
      patients (three in covered vs one in uncovered SEMS group, P = 0.607).
      CONCLUSIONS: In this exploratory trial, there were no statistically significant
      differences in stent patency, time-to-stent occlusion, patient survival, and
      complication rates between covered and uncovered SEMS groups. Larger confirmatory
      multicenter trial is needed for the clear conclusion (ClinicalTrials.gov:
      NCT01315522).

PMID- 27029891
TI  - Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues.
AB  - The inclusion of magnetic nanoparticles into biopolymer matrixes enables the
      preparation of magnetic field-responsive engineered tissues. Here we describe a
      synthetic route to prepare biocompatible core-shell nanostructures consisting of
      a polymeric core and a magnetic shell, which are used for this purpose. We show
      that using a core-shell architecture is doubly advantageous. First, gravitational
      settling for core-shell nanocomposites is slower because of the reduction of the
      composite average density connected to the light polymer core. Second, the
      magnetic response of core-shell nanocomposites can be tuned by changing the
      thickness of the magnetic layer. The incorporation of the composites into
      biopolymer hydrogels containing cells results in magnetic field-responsive
      engineered tissues whose mechanical properties can be controlled by external
      magnetic forces. Indeed, we obtain a significant increase of the viscoelastic
      moduli of the engineered tissues when exposed to an external magnetic field.
      Because the composites are functionalized with polyethylene glycol, the prepared
      bio-artificial tissue-like constructs also display excellent ex vivo cell
      viability and proliferation. When implanted in vivo, the engineered tissues show
      good biocompatibility and outstanding interaction with the host tissue. Actually,
      they only cause a localized transitory inflammatory reaction at the implantation
      site, without any effect on other organs. Altogether, our results suggest that
      the inclusion of magnetic core-shell nanocomposites into biomaterials would
      enable tissue engineering of artificial substitutes whose mechanical properties
      could be tuned to match those of the potential target tissue. In a wider
      perspective, the good biocompatibility and magnetic behavior of the composites
      could be beneficial for many other applications. 

PMID- 27029893
TI  - Potential of novel drug delivery strategies for the treatment of hyperlipidemia.
AB  - Emergence of hyperlipidemia in urban population of India and the world at large
      is very high and accounts to several fatal diseases. This condition is known to
      manifest elevated levels of lipids and/or lipoproteins. Serious limitations like
      inadequate solubility, less absorption, less bioavailability, ineffectiveness in
      lowering of cholesterol levels, patient incompliance and so on are noticed with
      majority of anti-hyperlipidemic drugs and dosage forms, which are used
      conventionally. To overcome these shortcomings, building technology platforms for
      development of appropriate dosage forms is the need of the hour. These efforts
      are required to maximize patient acceptability while maintaining safety,
      efficacy, accessibility and affordability. Hyperlipidemia, its types, etiology,
      pathophysiology and conventional dosage forms are discussed here. The current
      approaches and novel developments which illustrate controlled drug release and
      sustained therapeutic effect along with site specific and target oriented drug
      delivery with better patient compliance are also reviewed critically. Despite the
      incentives provided by the efforts of formulation scientists, there is still a
      need for implementation of pharmaceutical technologies that enable to combat
      limitations of anti-hyperlipidemic drugs and conventional dosage forms associated
      with it. The present review emphasize on applications of novel drug delivery
      systems in pharmacotherapy of anti-hyperlipidemic drugs demonstrating the
      advantages and disadvantages.

PMID- 27029892
TI  - Greater Depressive Symptoms and Higher Viral Load Are Associated with Poor
      Physical Function among Latino Men Living with HIV.
AB  - Physical function limitations have been associated with poor health outcomes,
      which have a negative impact on quality of life of older individuals. This study
      examined the association between depression, viral load, and acculturation with
      physical function among Latino men living with HIV. A secondary data analysis was
      performed using a cross-sectional data of 146 Latino immigrant men living with
      HIV in New York City and Washington, DC. Physical function was measured using the
      Short-Form Health Survey (SF-12). Uncontrolled HIV infection and depression were
      associated with worse physical function, thus implying the importance of adequate
      health care to address these conditions. Preserving physical function should
      start during middle adulthood, particularly among people living with HIV because
      of their greater risk of developing age-related challenges such as depression,
      diabetes, cardiovascular diseases among others. This study informs future
      interventions to preserve physical function and achieve the goal of successful
      aging.

PMID- 27029894
TI  - Clinical spectrum and survival analysis of 145 cases of HIV-negative Castleman's
      disease: renal function is an important prognostic factor.
AB  - Castleman's disease (CD) is a rare lymphoproliferative disorder with clinical
      features and prognostic factors that are incompletely characterized. This
      retrospective single-center study reviewed the largest HIV-negative CD patient
      cohort (n = 145) to date. By clinical classification, we identified 69 patients
      (47.6%) as unicentric CD (UCD) and 76 patients (52.4%) as multicentric CD (MCD).
      Pathological classification identified 74 patients (51.0%) with the hyaline
      vascular variant, 51 patients (35.2%) with the plasma-cell variant, and 20
      patients (13.8%) with a mixed variant. After a median follow-up duration of 58
      months (range, 1-180 months), the 1-year and 5-year survival rates were 95.1% and
      91.0%, respectively. UCD patients exhibited significantly better survival (1-year
      and 5-year survival rates of 98.5% and 97.1%, respectively) compared with MCD
      patients (1-year and 5-year survival rates of 92.1% and 85.5%, respectively; p =
      0.005). By univariate and multivariate Cox regression analyses, the estimated
      glomerular filtration rate < 60 ml/min (with the MDRD equation; hazard ratio =
      4.60; 95% confidence interval, 1.50-14.12; p = 0.008) was clinically significant
      and represented an independent predictor for death in MCD patients. In summary,
      this large-scale study suggests that UCD patients enjoy better survival than MCD
      patients and that renal function is an important prognostic factor for MCD
      patients. 

PMID- 27029895
TI  - Role of Telomeres and Telomerase in Aging and Cancer.
AB  - Telomeres progressively shorten throughout life. A hallmark of advanced
      malignancies is the ability for continuous cell divisions that almost universally
      correlates with the stabilization of telomere length by the reactivation of
      telomerase. The repression of telomerase and shorter telomeres in humans may have
      evolved, in part, as an anticancer protection mechanism. Although there is still
      much we do not understand about the regulation of telomerase, it remains a very
      attractive and novel target for cancer therapeutics. This review focuses on the
      current state of advances in the telomerase area, identifies outstanding
      questions, and addresses areas and methods that need refinement. SIGNIFICANCE:
      Despite many recent advances, telomerase remains a challenging target for cancer
      therapy. There are few telomerase-directed therapies, and many of the assays used
      to measure telomeres and telomerase have serious limitations. This review
      provides an overview of the current state of the field and how recent advances
      could affect future research and treatment approaches. Cancer Discov; 6(6); 584
      93. (c)2016 AACR.

PMID- 27029896
TI  - Plasma cell alloantigen ENPP1 is expressed by a subset of human B cells with
      potential regulatory functions.
AB  - Plasma cell alloantigen 1 (PC1), also known as ENPP1 (ectonucleotide
      pyrophosphatase/phosphodiesterase 1), is an enzyme involved primarily in
      hydrolysis of adenosine triphosphate at the cell surface. Although the expression
      pattern of PC1 is relatively broad, its expression in B cells is found at
      significant levels only in terminally differentiated germinal center B cells,
      plasma cells and a subset of B-1a cells in mice. Here we describe studies
      designed to determine whether expression of PC1 might define novel populations of
      human B cells with similarities to mouse B cells. We found that PC1 is expressed
      in small populations of human B lineage cells in peripheral blood, cord blood,
      tonsils, bone marrow and pediatric peritoneal fluid, with the highest levels in
      plasma cells. The characteristics of human PC1(+) B cells differ from mouse
      peritoneal B-1a subsets and from features of the human CD20(+)CD27(+)CD43(+)CD70(
      ) B-cell subset proposed to be human B-1 cells. Expression of PC1 was greatly
      increased in B cells stimulated with the combination of CD40 ligand, interleukin
      (IL)-4 and IL-21. In addition, PC1(+) B cells activated CD4(+) T regulatory
      cells. ENPP1 thus defines a subset of human B cells that differs significantly
      from mouse peritoneal B-1a and proposed human B-1 cells.

PMID- 27029897
TI  - Knowledge, risk perception and attitudes toward vaccination among Austrian health
      care workers: A cross-sectional study.
AB  - The aim of this study was to evaluate the vaccination coverage of Austrian health
      care workers (HCWs), their knowledge concerning the current guideline on
      vaccination for HCWs and their attitudes toward vaccination. A cross-sectional
      survey was performed by distributing 200 questionnaires among the nursing staff
      of several medical wards and intensive care units of the Vienna General Hospital.
      116 questionnaires were returned for analysis with 77.4% female and 22.6% male
      participants. While certain vaccines like hepatitis B, tetanus and polio had high
      vaccination rates of up to 94% and good knowledge concerning the vaccination
      status, other vaccines like measles (59.8%), mumps (60.7%), rubella (70.5%),
      influenza (42.1%) or pertussis (58.2%) showed much lower coverage. The main
      sources of information were nursing school (59.1%), secondary school (46.1%),
      parents (45.2%) and media in general (45.2%). Only 21.9% of HCWs claimed to know
      the current guideline on vaccination. Those who knew the guideline were
      significantly more likely to consider certain vaccines like measles, mumps,
      rubella, diphtheria, polio and varicella as recommended (p <= 0.04). The most
      important reasons for receiving vaccination were self-protection (87.5%),
      prevention of epidemics (54.5%), protection of others (55.4%) and of patients
      (42.9%). Fear of side effects (67.2%), negative experiences with vaccines
      (22.4%), the additional doctor's appointment (20.7%) and considering vaccines as
      an invention by the pharmaceutical industry (19%) were hindering factors for
      vaccination of HCWs. Considering the essential role of HCWs in preventing
      diseases, this study noted a remarkable lack of information on vaccination in
      this profession.

PMID- 27029898
TI  - Participant Roles in Bullying Among Dutch Adolescents With Autism Spectrum
      Disorders.
AB  - This study investigated whether participant roles (i.e., bully, assistant,
      follower, defender, outsider, victim) identified in bullying among normative
      groups of adolescents educated in regular education could also be found among
      adolescents with autism spectrum disorders (ASD) educated in special education
      classrooms. Relationships between the participant roles and three social status
      measures (social preference, social impact, and popularity) were also examined.
      There were 260 Dutch adolescents with ASD, ages 12-18 (M = 13.75, SD = 1.42; 224
      boys, 36 girls), and 743 Dutch typically developing (TD) adolescents, ages 11-17
      (M = 13.41, SD = 1.24; 380 boys, 363 girls) who filled out questionnaires during
      classroom testing sessions conducted by the first author and trained
      (under)graduate students. Participant roles could be distinguished, although role
      distributions differed across groups and across sexes. There were more outsiders
      and defenders, and fewer followers among boys with ASD than among TD boys. Among
      girls with ASD, there were more victims than among TD girls. Students with ASD
      could more often be assigned multiple roles and were less often uninvolved than
      TD students. The relationships between participant roles and social status
      measures also differed across groups and across sexes. Whereas bullying is
      considered a universal social phenomenon, the existence of participant roles in
      bullying situations might be considered universal, as well. Apparently, the
      social difficulties of students with ASD do not seem to prevent them from taking
      on various participant roles in bullying situations. Additional practical
      implications are discussed.

PMID- 27029899
TI  - Association between tensin 1 and p130Cas at focal adhesions links actin inward
      flux to cell migration.
AB  - Cell migration is a highly dynamic process that plays pivotal roles in both
      physiological and pathological processes. We have previously reported that
      p130Cas supports cell migration through the binding to Src as well as
      phosphorylation-dependent association with actin retrograde flow at focal
      adhesions. However, it remains elusive how phosphorylated Cas interacts with
      actin cytoskeletons. We observe that the actin-binding protein, tensin 1, co
      localizes with Cas, but not with its phosphorylation-defective mutant, at focal
      adhesions in leading regions of migrating cells. While a truncation mutant of
      tensin 1 that lacks the phosphotyrosine-binding PTB and SH2 domains (tensin 1
      SH2PTB) poorly co-localizes or co-immunoprecitates with Cas, bacterially
      expressed recombinant tensin 1-SH2PTB protein binds to Casin vitroin a Cas
      phosphorylation-dependent manner. Furthermore, exogenous expression of tensin 1
      SH2PTB, which is devoid of the actin-interacting motifs, interferes with the Cas
      driven cell migration, slows down the inward flux of Cas molecules, and impedes
      the displacement of Cas molecules from focal adhesions. Taken together, our
      results show that tensin 1 links inwardly moving actin cytoskeletons to
      phosphorylated Cas at focal adhesions, thereby driving cell migration. 

PMID- 27029900
TI  - Response of garlic (Allium sativum L.) bolting and bulbing to temperature and
      photoperiod treatments.
AB  - This research was conducted to evaluate the effect of temperature and photoperiod
      treatments on the bolting and bulb formation of three local garlic cultivars
      (cvs) in two consecutive years. Naturally vernalized plants of cvs G107, G025 and
      G064 were transplanted into growth chambers and subjected to various combinations
      of temperature [T15/10, 15 degrees C/10 degrees C; T20/15, 20 degrees C/15
      degrees C and T25/18, 25 degrees C/18 degrees C (day/night)] and photoperiod (L8,
      8 h and L14,14 h) treatments. Plant growth, endogenous phytohormone and methyl
      jasmonate (MeJA) levels, along with the bolting and yield of garlic were
      evaluated. The experimental results from two consecutive years indicated that
      higher temperature (20 degrees C or 25 degrees C) and longer photoperiod (14 h)
      treatments significantly enhanced the garlic bolting, bulbing and cloving with a
      shorter growth period and a higher bulb weight. Moreover, the endogenous
      phytohormone and MeJA levels in the test plants were significantly increased by
      the higher temperature (25 degrees C for the phytohormone level; 20 degrees C for
      the MeJA level) and longer photoperiod [14 h, except for abscisic acid (ABA),
      which had the highest level at 8 h] conditions and were decreased by the lowest
      test temperature (15 degrees C) and shorter photoperiod (8 h, except for ABA)
      conditions. This response coincided with that of the bulbing index, bolting rate,
      growth period and bulb weight. In addition, plants treated under the conditions
      of 20 degrees C/15 degrees C-14 h and 25 degrees C/18 degrees C-14 h produced the
      highest phytohormone levels (except for ABA) for cvs G025 and G064, respectively,
      and showed the best bolting and bulbing behavior. It is reasonable to assume that
      endogenous phytohormone (especially gibberellic acid) and MeJA levels are highly
      related to garlic bolting and bulbing, which might lead to the different
      responses of the three studied cultivars to the combination of temperature and
      photoperiod treatments. Furthermore, cvs G107 and G025 bolt well and have better
      bulb formation under 20 degrees C-14 h conditions, while the conditions of 25
      degrees C-14 h are critical for the bolting and bulbing of cv. G064. 

PMID- 27029901
TI  - Knockdown of TC-1 enhances radiosensitivity of non-small cell lung cancer via the
      Wnt/beta-catenin pathway.
AB  - Thyroid cancer 1 (TC-1, C8ofr4) is widely expressed in vertebrates and associated
      with many kinds of tumors. Previous studies indicated that TC-1 functions as a
      positive regulator in the Wnt/beta-catenin signaling pathway in non-small cell
      lung cancer (NSCLC). However, its exact role and regulation mechanism in
      radiosensitivity of NSCLC are still unclear. The expression level of TC-1 was
      measured by qRT-PCR and western blot in NSCLC cell lines. Proliferation and
      apoptosis of NSCLC cells in response to TC-1 knockdown or/and radiation were
      determined by MTT assay and flow cytometry, respectively. The activation of the
      Wnt/beta-catenin signaling pathway was further examined by western blotin
      vitroandin vivo Compared to TC-1 siRNA or radiotherapy alone, TC-1 silencing
      combined with radiation inhibited cell proliferation and induced apoptosis in
      NSCLC cell lines by inactivating of the Wnt/beta-catenin signaling pathway.
      Furthermore, inhibition of the Wnt/beta-catenin signaling pathway by XAV939, a
      Wnt/beta-catenin signaling inhibitor, contributed to proliferation inhibition and
      apoptosis induction in NSCLC A549 cells. Combinative treatment of A549 xenografts
      with TC-1 siRNA and radiation caused significant tumor regression and
      inactivation of the Wnt/beta-catenin signaling pathway relative to TC-1 siRNA or
      radiotherapy alone. The results fromin vitroandin vivostudies indicated that TC-1
      silencing sensitized NSCLC cell lines to radiotherapy through the Wnt/beta
      catenin signaling pathway. 

PMID- 27029902
TI  - Biosafety of biotechnologically important microalgae: intrinsic suicide switch
      implementation in cyanobacterium Synechocystis sp. PCC 6803.
AB  - In recent years, photosynthetic autotrophic cyanobacteria have attracted interest
      for biotechnological applications for sustainable production of valuable
      metabolites. Although biosafety issues can have a great impact on public
      acceptance of cyanobacterial biotechnology, biosafety of genetically modified
      cyanobacteria has remained largely unexplored. We set out to incorporate
      biocontainment systems in the model cyanobacteriumSynechocystissp. PCC 6803.
      Plasmid-encoded safeguards were constructed using the nonspecific nuclease NucA
      fromAnabaenacombined with different metal-ion inducible promoters. In this
      manner, conditional lethality was dependent on intracellular DNA degradation for
      regulated autokilling as well as preclusion of horizontal gene transfer. In cells
      carrying the suicide switch comprising thenucAgene fused to a variant of
      thecopMpromoter, efficient inducible autokilling was elicited. Parallel to
      nuclease-based safeguards, cyanobacterial toxin/antitoxin (TA) modules were
      examined in biosafety switches. Rewiring ofSynechocystisTA
      pairsssr1114/slr0664andslr6101/slr6100for conditional lethality using metal-ion
      responsive promoters resulted in reduced growth, rather than cell killing,
      suggesting cells could cope with elevated toxin levels. Overall, promoter
      properties and translation efficiency influenced the efficacy of biocontainment
      systems. Several metal-ion promoters were tested in the context of safeguards,
      and selected promoters, including anrsBvariant, were characterized by beta
      galactosidase reporter assay. 

PMID- 27029905
TI  - Confidence in delegation and leadership of registered nurses in long-term-care
      hospitals.
AB  - BACKGROUND AND AIMS: Effective delegation improves job satisfaction,
      responsibility, productivity and development. The ageing population demands more
      nurses in long-term-care hospitals. Delegation and leadership promote cooperation
      among nursing staff. However, little research describes nursing delegation and
      leadership style. We investigated the relationship between registered nurses'
      delegation confidence and leadership in Korean long-term-care hospitals. METHODS:
      Our descriptive correlational design sampled 199 registered nurses from 13 long
      term-care hospitals in Korea. Instruments were the Confidence and Intent to
      Delegate Scale and Multifactor Leadership Questionnaire. RESULTS: Confidence in
      delegation significantly aligned with current-unit clinical experience, length of
      total clinical-nursing experience, delegation-training experience and leadership.
      Transformational leadership was the most statistically significant factor
      influencing delegation confidence. IMPLICATIONS FOR NURSING MANAGEMENT: When
      effective delegation integrates with efficient leadership, staff can deliver
      optimal care to long-term-care patients.

PMID- 27029904
TI  - KCa3.1 mediates dysfunction of tubular autophagy in diabetic kidneys via
      PI3k/Akt/mTOR signaling pathways.
AB  - Autophagy is emerging as an important pathway in many diseases including diabetic
      nephropathy. It is acknowledged that oxidative stress plays a critical role in
      autophagy dysfunction and diabetic nephropathy, and KCa3.1 blockade ameliorates
      diabetic renal fibrosis through inhibiting TGF-beta1 signaling pathway. To
      identify the role of KCa3.1 in dysfunctional tubular autophagy in diabetic
      nephropathy, human proximal tubular cells (HK2) transfected with scrambled or
      KCa3.1 siRNAs were exposed to TGF-beta1 for 48 h, then autophagosome formation,
      the autophagy marker LC3, signaling molecules PI3K, Akt and mTOR, and oxidative
      stress marker nitrotyrosine were examined respectively. In vivo, LC3,
      nitrotyrosine and phosphorylated mTOR were examined in kidneys of diabetic
      KCa3.1+/+ and KCa3.1-/- mice. The results demonstrated that TGF-beta1 increased
      the formation of autophagic vacuoles, LC3 expression, and phosphorylation of
      PI3K, Akt and mTOR in scrambled siRNA transfected HK2 cells compared to control
      cells, which was reversed in KCa3.1 siRNA transfected HK2 cells. In vivo,
      expression of LC3 and nitrotyrosine, and phosphorylation of mTOR were
      significantly increased in kidneys of diabetic KCa3.1+/+ mice compared to non
      diabetic mice, which were attenuated in kidneys of diabetic KCa3.1-/- mice. These
      results suggest that KCa3.1 activation contributes to dysfunctional tubular
      autophagy in diabetic nephropathy through PI3K/Akt/mTOR signaling pathways. 

PMID- 27029906
TI  - Enantioselective Assembly of Spirolactones through NHC-Catalyzed Remote gamma
      Carbon Addition of Enals with Isatins.
AB  - A chiral N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] annulation of beta
      methyl substituted enals with isatins was developed to construct six-membered
      spirolactones bearing highly congested quaternary carbon stereocentersin good
      yields and high enantioselectivities. The strategy realized a challenging remote
      gamma-carbon addition of enals and chiral control of beta-methyl substituted
      enals in the presence of the NHC catalyst only.

PMID- 27029907
TI  - Cardiac arrest in Antarctica--a successful outcome.

PMID- 27029908
TI  - Assessment of the role of international travel and unauthorized immigration on
      measles importation to the United States.
AB  - BACKGROUND: Concerns have been raised about unauthorized immigrants importing
      measles to the United States (US). This potential risk has not been rigorously
      evaluated nor compared with the potential risk of measles importation by US
      residents traveling internationally or international travellers coming to the US.
      We compared the potential risk of measles importation from each of these
      populations. METHODS: Using a cross-sectional, ecological design, we compared
      country-level measles vaccination and incidence data, for top (i) US resident
      international travel destinations, (ii) US-bound international travellers' home
      countries and (iii) home countries of unauthorized immigrants to the US. RESULTS:
      In 2014, US residents made 52.5 million trips to one of the top 10 international
      destinations. Five of these countries (10,958,000 US resident trips) had average
      first-dose measles vaccine coverage below 90%, and five (9,881,000 US resident
      trips) had average measles incidence over 1 case/100,000 population. Two of the
      10 top US-bound international travellers' home countries (5,597,259 international
      visitors) had average first-dose measles vaccine coverage below 90%, whereas five
      (13,333,545 international visitors) had average annual measles incidence over 1
      case/100,000 population). In 2012, of 11.2 million unauthorized immigrants living
      in the US, 8.9 million (79.0%) were born in one of the top 10 unauthorized
      immigrant home countries. Four of those countries had average first-dose measles
      vaccine coverage below 90% (1.3 million unauthorized immigrants), whereas three
      of these countries had average measles incidence over 1 case/100,000 population
      (950,000 unauthorized immigrants). Overall, there are 10 times more annual US
      visitors to high measles incidence countries than there are unauthorized
      immigrants in the US from high measles incidence countries. CONCLUSIONS: Efforts
      to prevent reestablishment of indigenous measles transmission in the US should
      focus on evidence-based risk assessments, highlighting a greater potential
      measles importation risk of from US residents travelling internationally than
      unauthorized immigrants coming to the US.

PMID- 27029909
TI  - Pre-travel advice seeking from GPs by travellers with chronic illness seen at a
      travel clinic.
AB  - PURPOSE: Travellers are ageing and frequently report chronic illness. Pre-travel
      health advice is crucial, particularly in this subgroup, and general
      practitioners (GPs) are first in line for treatment adjustment before departure.
      Our aim is to evaluate pre-travel health advice seeking from GPs by travellers
      with chronic illness seen at a travel clinic. METHODS: A cross-sectional
      observational survey using a questionnaire was conducted between August 2013 and
      July 2014 in travellers attending the travel medicine clinic of a tertiary
      university hospital in France. RESULTS: During the study, 2019 travellers were
      included. Mean age was 39.4 years (+/-18.8). Three hundred and ninety-one (19.4%)
      travellers reported a history of a chronic illness. Arterial hypertension and
      diabetes mellitus were the most frequently reported illnesses, affecting,
      respectively, 168 (8.3%) travellers and 102 (5.1%). Hajj pilgrims were more
      likely to report a history of chronic illness than other travellers. Only 810
      (40.1%) travellers sought pre-travel advice from their GP. Six hundred and fifty
      two (40.1%) healthy travellers and 158 (40.5%) travellers reporting chronic
      illness sought pre-travel advice from their GP (P = 0.96). CONCLUSION: Travellers
      with a history of chronic illness do not seek pre-travel health advice from their
      GP more frequently than healthy travellers. Travel health specialists are
      generally not the best practitioners to manage the care of underlying medical
      conditions presenting risks during travel. However, GPs offer continuity and
      disease management expertise to improve the specificity of pre-travel planning.
      Thus, ongoing collaboration between the traveller, GP and travel health
      specialist is likely to yield the best outcomes.

PMID- 27029910
TI  - Testing the accuracy ratio of the Spatio-Temporal Epidemiological Modeler (STEM)
      through Ebola haemorrhagic fever outbreaks.
AB  - Mathematical modelling is an important tool for understanding the dynamics of the
      spread of infectious diseases, which could be the result of a natural outbreak or
      of the intentional release of pathogenic biological agents. Decision makers and
      policymakers responsible for strategies to contain disease, prevent epidemics and
      fight possible bioterrorism attacks, need accurate computational tools, based on
      mathematical modelling, for preventing or even managing these complex situations.
      In this article, we tested the validity, and demonstrate the reliability, of an
      open-source software, the Spatio-Temporal Epidemiological Modeler (STEM),
      designed to help scientists and public health officials to evaluate and create
      models of emerging infectious diseases, analysing three real cases of Ebola
      haemorrhagic fever (EHF) outbreaks: Uganda (2000), Gabon (2001) and Guinea
      (2014). We discuss the cases analysed through the simulation results obtained
      with STEM in order to demonstrate the capability of this software in helping
      decision makers plan interventions in case of biological emergencies.

PMID- 27029911
TI  - Assessment of the severity of Ebola virus disease in Sierra Leone in 2014-2015.
AB  - The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in
      scale, and Sierra Leone is the most severely affected country. The case fatality
      risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the
      severity of infections in confirmed and probable EVD cases in Sierra Leone.
      Proportional hazards regression models were used to investigate factors
      associated with the risk of death in EVD cases. In total, there were 17 318 EVD
      cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the
      probable and confirmed EVD cases with a reported final outcome, a total of 2536
      deaths and 886 recoveries were reported. CFR and HFR estimates were 74.2% [95%
      credibility interval (CrI) 72.6-75.5] and 68.9% (95% CrI 66.2-71.6),
      respectively. Risks of death were higher in the youngest (0-4 years) and oldest
      (?60 years) age groups, and in the calendar month of October 2014. Sex and
      occupational status did not significantly affect the mortality of EVD. The CFR
      and HFR estimates of EVD were very high in Sierra Leone.

PMID- 27029912
TI  - Randomized Trial of Interpersonal Psychotherapy and Cognitive Behavioral Therapy
      for Major Depressive Disorder in a Community-Based Psychiatric Outpatient Clinic.
AB  - BACKGROUND: Interpersonal psychotherapy (IPT) and cognitive behavioral therapy
      (CBT) are both evidence-based treatments for major depressive disorder (MDD).
      Several head-to-head comparisons have been made, mostly in the United States. In
      this trial, we compared the two treatments in a small-town outpatient psychiatric
      clinic in Sweden. The patients had failed previous primary care treatment and had
      extensive Axis-II comorbidity. Outcome measures were reduction of depressive
      symptoms and attrition rate. METHODS: Ninety-six psychiatric patients with MDD
      (DSM-IV) were randomized to 14 sessions of CBT (n = 48) or IPT (n = 48). A
      noninferiority design was used with the hypothesis that IPT would be noninferior
      to CBT. A three-point difference on the Beck Depression Inventory-II (BDI-II) was
      used as noninferiority margin. RESULTS: IPT passed the noninferiority test. In
      the ITT group, 53.5% (23/43) of the IPT patients and 51.0% (24/47) of the CBT
      patients were reliably improved, and 20.9% (9/43) and 19.1% (9/47), respectively,
      were recovered (last BDI score <10). The dropout rate was significantly higher in
      CBT (40%; 19/47) compared to IPT (19%; 8/43). Statistically controlling for
      antidepressant medication use did not change the results. CONCLUSIONS: IPT was
      noninferior to CBT in a sample of depressed psychiatric patients in a community
      based outpatient clinic. CBT had significantly more dropouts than IPT, indicating
      that CBT may be experienced as too demanding. Since about half the patients did
      not recover, there is a need for further treatment development for these
      patients. The study should be considered an effectiveness trial, with strong
      external validity but some limitations in internal validity.

PMID- 27029913
TI  - Interprofessional curriculum development achieves results: Initial evidence from
      a dementia-care protocol.
AB  - This report describes the outcomes of a five-day, protocol-based
      interprofessional education (IPE) initiative to prepare undergraduate medical,
      nursing, and paramedic students for collaborative work with adults with dementia.
      Clinical placements provided a structured and supervised IPE experience for 127
      students in two Residential Aged Care Facilities (RACFs) in Hobart, Australia,
      during 2013 and 2014. The IPE activity was based on a seven-step protocol
      formulated by an interprofessional team of educators and aged care practitioners
      that revolved around collaborative assessments of adults with complex health
      needs. This article describes the IPE protocol and presents the results of a pre-
      and post-placement attitude questionnaire and knowledge quiz administered to
      evaluate student attitudes towards IPE and knowledge of dementia. Data suggest
      that a five-day, supervised, and protocol-based IPE experience in a dementia-care
      setting can inculcate positive changes in student attitudes about collaborative
      practice and may encourage dementia-related learning outcomes. 

PMID- 27029916
TI  - The effects of oxidative stress following ischemia-reperfusion injury.

PMID- 27029915
TI  - The cytokine interleukin-26 as a biomarker in pediatric asthma.
AB  - In this pilot study, we examined associations between local interleukin (IL)-26,
      disease severity and biomarkers of Th2-mediated inflammation in a well-defined
      cohort of pediatric patients (14 years median age, 41 % females) with controlled
      (n = 28) or uncontrolled (n = 48) asthma. Sputum IL-26 protein concentrations
      (ELISA) reflected disease control in patients without local (low exhaled nitric
      oxide) or systemic (low blood eosinophils) signs of eosinophilic inflammation.
      Moreover, sputum-IL-26 concentrations correlated with those of blood neutrophils.
      Our study indicates that IL-26 is a potential biomarker of disease severity in
      pediatric asthma without signs of Th2-mediated inflammation.

PMID- 27029917
TI  - Accuracy of intraoperative frozen section for the evaluation of ovarian
      neoplasms: an institutional experience.
AB  - BACKGROUND: Ovarian neoplasms are a heterogeneous group of tumors including
      surface epithelial, germ cell and sex cord stromal tumors with a subset having
      low malignant potential (borderline tumors). While the surgical management plan
      differs in different categories of tumors, preoperative diagnosis is seldom
      available. In these circumstances, the role of frozen section becomes invaluable.
      In the current study, we aimed to evaluate the accuracy of the frozen section of
      ovarian tumors in our setup. METHODS: It was a retrospective study involving 141
      cases of ovarian tumors undergoing surgical resection with frozen section
      evaluation from January 2009 to December 2014. After gross examination, one to
      five blocks were prepared on the frozen section depending upon the size of the
      specimen. After frozen section reporting, specimens were processed routinely for
      final paraffin section evaluation. Results of frozen and paraffin sections were
      categorized in benign, borderline, and malignant, and accuracy of frozen section
      was determined. RESULTS: Out of 141 cases, 107 were diagnosed as benign on final
      (paraffin) examination, while 6 were borderline and 28 were malignant. Out of 107
      benign cases, 45 were non-neoplastic cystic lesions of the ovary including
      endometriotic, follicular, and corpus luteal cysts. The most common benign
      neoplastic tumor was mature cystic teratoma (20 cases) followed by mucinous
      cystadenoma (19 cases), serous cystadenoma (14 cases), sex cord stromal tumors (8
      cases), and Brenner tumor (1 case). Among borderline cases, four cases were
      serous and two of mucinous neoplasms. The most common malignant neoplasm was
      serous carcinoma (11 cases) followed by mucinous carcinoma (6 cases). The overall
      accuracy of frozen section diagnosis is above 99 %. The sensitivity and
      specificity for benign tumors were found to be 100 and 97 %, respectively. The
      sensitivity and specificity for borderline tumors was 83 and 99 %, respectively,
      while for malignant tumors, it was 96 and 100 %, respectively. CONCLUSIONS: We
      found a high sensitivity and specificity of frozen section for the diagnosis of
      ovarian tumors and to determine its malignant potential. Therefore, it should
      always be used when the preoperative diagnosis is not definite to govern extent
      of surgical resection. However, under-diagnosis can occur in tumors of borderline
      category which can be minimized by increased sampling on the frozen section.

PMID- 27029918
TI  - Iron bioavailability from fresh cheese fortified with iron-enriched yeast.
AB  - PURPOSE: An iron-enriched yeast able to lyse at body temperature was developed
      for iron fortification of chilled dairy products. The aim was to evaluate iron
      (Fe) absorption from iron-enriched yeast or ferrous sulfate added to fresh
      cheese. METHODS: Two stable isotope studies with a crossover design were
      conducted in 32 young women. Fe absorption from fresh cheese fortified with iron
      enriched yeast (2.5 mg 58Fe) was compared to that from ferrous sulfate (2.5 mg
      57Fe) when ingested with fresh cheese alone or with fresh cheese consumed with
      bread and butter. Iron absorption was determined based on erythrocyte
      incorporation of isotopic labels 14 days after consumption of the last test meal.
      RESULTS: Geometric mean fractional iron absorption from fresh cheese fortified
      with iron-enriched yeast consumed alone was significantly lower than from the
      cheese fortified with FeSO4 (20.5 vs. 28.7 %; p = 0.0007). When the fresh cheese
      was consumed with bread and butter, iron absorption from both fortificants
      decreased to 6.9 % from the iron-enriched yeast compared to 8.4 % from ferrous
      sulfate. The relative bioavailability of the iron-enriched yeast compared to
      ferrous sulfate was 0.72 for the cheese consumed alone and 0.82 for cheese
      consumed with bread and butter (p = 0.157). CONCLUSIONS: Iron from iron-enriched
      yeast was 72-82 % as well absorbed as ferrous sulfate indicating that the yeast
      lysed during digestion and released its iron.

PMID- 27029921
TI  - Seafarer medicals: population health or private gain?

PMID- 27029919
TI  - Dietary fat may modulate adipose tissue homeostasis through the processes of
      autophagy and apoptosis.
AB  - PURPOSE: Obesity increases the risk of cardiovascular disease, type 2 diabetes
      mellitus and cancer development. Autophagy and apoptosis are critical processes
      for development and homeostasis in multicellular organisms and have been linked
      to a variety of disorders. We aimed to investigate whether the quantity and
      quality of dietary fat can influence these processes in the adipose tissue of
      obese people. METHODS: A randomized, controlled trial within the LIPGENE study
      assigned 39 obese people with metabolic syndrome to 1 of 4 diets: (a) a high
      saturated fatty acid diet, (b) a high-monounsaturated fatty acid (HMUFA) diet,
      and (c, d) two low-fat, high-complex carbohydrate diets supplemented with long
      chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12
      weeks each. RESULTS: We found an increase in the expression of autophagy-related
      BECN1 and ATG7 genes after the long-term consumption of the HMUFA diet (p = 0.001
      and p = 0.004, respectively) and an increase in the expression of the apoptosis
      related CASP3 gene after the long-term consumption of the LFHCC and LFHCC n-3
      diets (p = 0.001 and p = 0.029, respectively). CASP3 and CASP7 gene expression
      changes correlated with HOMA index. CONCLUSION: Our results suggest that the
      processes of autophagy and apoptosis in adipose tissue may be modified by diet
      and that the consumption of a diet rich in monounsaturated fat may contribute to
      adipose tissue homeostasis by increasing autophagy. They also reinforce the
      notion that apoptosis in adipose tissue is linked to insulin resistance. CLINICAL
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00429195.

PMID- 27029922
TI  - Improving cardiovascular health in Spanish seafarers.
AB  - BACKGROUND AND AIM: There is a high prevalence in the Spanish general population
      of some cardiovascular risk factors like overweight, obesity and
      hypercholesterolaemia. But there is lack of research on Spanish seafarers. On the
      other hand, there is strong evidence of the cardiovascular risk predictive value
      of some biomarkers. The purpose of this work was to study the convenience of the
      introduction of detailed diet questionnaires and the measurement of some
      biomarkers in the pre-embarkation medical examination. MATERIALS AND METHODS:
      Seafarers undergoing medical checkup during 2011 in Madrid, Spain (n = 334).
      Overweight and obese subjects received general advice on healthy diet and
      physical activity. Seventy-four of them were followed up in 2012 and 2013.
      Glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP),
      thyrotropin (TSH) and microalbuminuria were measured in two selected groups of
      patients in 2011. RESULTS: Overweight and obesity were present in 207 (62%)
      individuals of the studied population. Those followed up in 2012 and 2013 showed
      a reduction of body mass index, waist circumference and total cholesterol values.
      We observed risk value of HbA1c in 60 (35.5%) individuals with significant
      association to other cardiovascular risk factors. Microalbuminuria appeared in
      subjects with high blood pressure. High TSH and hs-CRP were not significantly
      present in our population. CONCLUSIONS: 1. Measurement of HbA1c during medical
      checkups improves early detection of cardiovascular risk in seafarers. 2.
      Individuals with overweight and obesity responded positively to medical advice
      and diminished their risk factors, thus it may be more effective to introduce
      detailed questionnaires on this issue.

PMID- 27029920
TI  - CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus
      aureus infection: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a
      serious infection resulting in 20-50 % 90-day mortality. The limitations of
      vancomycin, the current standard therapy for MRSA, make treatment difficult. The
      only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not
      been shown to be superior to vancomycin. Surprisingly, there has been consistent
      in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or
      daptomycin and an anti-staphylococcal beta-lactam antibiotic. There is also
      growing clinical data to support such combinations, including a recent pilot
      randomised controlled trial (RCT) that demonstrated a trend towards a reduction
      in the duration of bacteraemia in patients treated with vancomycin plus
      flucloxacillin compared to vancomycin alone. Our aim is to determine whether the
      addition of an anti-staphylococcal penicillin to standard therapy results in
      improved clinical outcomes in MRSA bacteraemia. METHODS/DESIGN: We will perform
      an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in
      Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older)
      with MRSA grown from at least one blood culture and able to be randomised within
      72 hours of the index blood culture collection will be eligible for inclusion.
      Participants will be randomised to vancomycin or daptomycin (standard therapy)
      given intravenously or to standard therapy plus 7 days of an anti-staphylococcal
      beta-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint
      will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent
      bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4)
      microbiological treatment failure. The recruitment target of 440 patients is
      based on an expected failure rate for the primary outcome of 30 % in the control
      arm and the ability to detect a clinically meaningful absolute decrease of 12.5
      %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients
      will not be evaluable for the primary endpoint. DISCUSSION: Key potential
      advantages of adding anti-staphylococcal beta-lactams to standard therapy for
      MRSA bacteraemia include their safety profile, low cost, and wide availability.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02365493 . Registered 24
      February 2015.

PMID- 27029923
TI  - Dental hygiene habits and oral health status of seafarers.
AB  - BACKGROUND: This study has assessed the dental hygiene habits and problems of
      seafarers and their attitudes/ perceptions regarding oral hygiene using a dental
      hygiene/habits questionnaire. MATERIALS AND METHODS: A research questionnaire on
      oral hygiene habits was prepared along with a summary of all the questions and
      sent to ships via e-mail by Centro Internazionale Radio Medico (CIRM) networks.
      CIRM, is the Italian Telemedical Maritime Assistance Service (TMAS), and
      represents the Centre with the largest number of seafarers assisted on board
      ships worldwide. CIRM proposed the questionnaire to all ships (n = 1,198) asking
      for medical advice from 1 July 2014 till 31 October 2014. Two dental
      professionals were involved in the development and analysis of the questionnaire.
      RESULTS: Seafarers are at risk of several dental health problems due to their
      oral hygiene and dietary habits, smoking and alcohol consumption, poor oral
      hygiene knowledge and motivation. Dietary habits during voyages were also
      questionable and seafarers consume food rich in fermentable carbohydrates, which
      is a major risk factor for dental caries. CONCLUSIONS: Seafarers need better oral
      hygiene education and care to enable them to manage their oral health in a better
      way. Life at the sea, under challenging circumstances is not without stress, that
      is why it is important that seafarers are given complete information about
      correct oral hygiene protocols and dental hygiene and the advantages for their
      health of keeping a healthy mouth.

PMID- 27029924
TI  - An ontology-based consultation system to support medical care on board seagoing
      vessels.
AB  - BACKGROUND: A realistic possibility to obtain medical care for patients located
      in remote sites such as seagoing vessels, in which health professionals are not
      available, is to contact a doctor via telecommunication systems. In general, the
      medical knowledge of who on board ships is in charge of medical care is quite
      limited and therefore, in a first level telemedical consultation, the flow of
      information should be correct and its efficiency should be maximised. This paper
      describes an application conceived to improve requests of medical assistance from
      sailing ships. The ultimate objective of this system is a) to standardise as much
      as possible the requests of medical advice at a distance, b) to overcome language
      barriers and jammed-related troubles that could make difficult or not
      understandable a telephone conversation. MATERIALS AND METHODS: The application
      is based on a software engine extracting data from an ontological knowledgebase
      built ad hoc using Protege. RESULTS: Compared to the conventional consultation
      systems based on telephone and e-mail, the proposed device is more accurate and
      complete in terms of information contained in the request of assistance.
      Moreover, data received by the medical centre can be more easily managed, as they
      can be standardised. CONCLUSIONS: The system described here allows people
      responsible of medical care on board ships to forward detailed requests of
      assistance containing symptom-guided information on patient clinical conditions.
      This may represent an innovative tool for medical consultations at distance
      allowing the remote centre to provide more precise and quicker medical advice.

PMID- 27029925
TI  - Accidents on board merchant ships. Suggestions based on Centro Internazionale
      Radio Medico (CIRM) experience.
AB  - BACKGROUND: This statistical study was performed to find out the occurrence of
      accidents on board ships assisted by Centro Internazionale Radio Medico (CIRM)
      during the years 2010-2015, with the aim of providing suggestions in accident
      prevention, based on such a wide experience. MATERIALS AND METHODS: The case
      histories of CIRM in the years 2010-2015 were examined. The total number of
      accidents per year was calculated and compared as a percentage with the total
      number of cases assisted by CIRM per year. RESULTS: The incidence of accidents on
      board in these years ranged between 14.4% and 18.4% of total cases assisted per
      year, which is constantly increasing. The most common injuries on board among
      cases treated by CIRM were contusions and wounds. Also burns and eye injuries
      were significantly represented. Multiple injuries and head injuries were found to
      be the most frequent cause of death on board due to an accident. CONCLUSIONS:
      More information on the occurrence and type of accidents and on the body injured
      areas should represent the basis for developing strategies and campaigns for
      their prevention.

PMID- 27029926
TI  - Telemedical Maritime Assistance Service (TMAS) to Swedish merchant and passengers
      ships 1997-2012.
AB  - BACKGROUND: Telemedical Maritime Assistance Service (TMAS) for seafarers and
      traveling passengers is important and can be crucial for the optimal medical
      treatment on board ships. The aim of this study was to analyse and to compare the
      data from consultations and evacuations from merchant ships and passenger ferries
      for possible improvements. MATERIALS AND METHODS: Data for seafarers from 1997,
      2002 and 2007 and for passengers on Swedish ferries for the years 2007, 2009,
      2011 and 2012 from the Swedish Radio Medical were studied. Symptoms and diseases
      were classified according to the International Classification for Primary Care
      (ICPC-2). The distribution of symptoms, accidents and diseases,
      treatments/actions taken, evacuations and the communication forms were analysed.
      RESULTS: One thousand ninety-five contacts for seafarers from merchant ships and
      651 passenger patients from Swedish ferries were analysed. While the evacuations
      for the seafarers gradually decreased over the years from 18% in 1997 to 14% in
      2007, still 39.5% of the passenger patient contacts were evacuated mainly by
      helicopters and 70 patients were picked up by an ambulance on the quay. Accidents
      were 20% for seafarers and 25% for passengers of the contacts. Evacuations for
      passengers were mainly in the diagnostic groups: unspecific (A), digestive (D),
      cardiology (K), musculoskeletal (L) and neurology (N). The use of VHF, radio
      communications and fax machines have been greatly reduced while the use of e-mail
      and satellite phone increased. CONCLUSIONS: No significant differences in reasons
      for contact or actions over the years have been identified. The evacuations of
      seafarers decreased over the years but was stable among the passenger patients
      (39%). The circumstances and reasons behind the evacuations should be analysed
      for prevention. Standard forms and digital images for documentation can
      facilitate knowledge exchange and further studies.

PMID- 27029927
TI  - Zika - another threat on the epidemiological map of the world.
AB  - Zika fever is an acute infectious disease caused by the Zika virus (ZIKV) of the
      Flaviviridae family and Flavivirus genus. It is transmitted by day-time active
      Aedes mosquitoes, and potentially by sexual contacts, blood transfusion, and from
      mother to foetus (resulting in microcephaly in a child). ZIKV was first isolated
      from a macaque monkey in the Zika forest in Uganda in 1947. The first case of the
      Zika fever in a human was recorded in Nigeria in 1954. Until 2007 only 14 cases
      of the disease were confirmed worldwide. In 2007, there was an outbreak of the
      Zika fever in Micronesia (Yap Island) with an estimated 5,000 cases. Between 2013
      and 2015 a further outbreak of the disease occurred in the Pacific islands: in
      French Polynesia, New Caledonia, Cook Islands, Easter Island, and Solomon
      Islands. In 2015, the Zika fever spread to Brazil and more than 20 other
      countries in the South and Central America. Until March 2016, an estimated 1.6
      million autochthonous cases of Zika have been reported globally, with
      approximately 1.5 million cases recorded in Brazil. Typically, 80% of Zika
      infections are asymptomatic. The most common symptoms of the disease include
      fever, maculopapular rash, muscle and joint pain, conjunctivitis. Zika fever can
      be diagnosed on the basis of clinical signs (it must be differentiated from
      dengue, chikungunya), ZIKV identification is also possible by the application of
      polymerase chain reaction in acutely ill patients and the detection of specific
      IgM and IgG antibodies to ZIKV. Until today, there is no effective antiviral
      treatment or an effective vaccine against Zika fever (in case of an infection
      only symptomatic treatment is applied). In August 2016 in Rio de Janeiro (Brazil)
      Summer Olympic Games will take place, attracting thousands of athletes and
      spectators. The fight against the Zika fever and the race against time have
      gained momentum. 

PMID- 27029928
TI  - A case of acalculous cholecystitis in the course of dengue fever in a traveller
      returned from Brazil.
AB  - BACKGROUND: Dengue is the second cause of fever after malaria in travellers
      returning from the tropics. The infection may be asymptomatic or it may manifest
      itself with fever only, some patients, however, may develop haemorrhagic symptoms
      and shock. MATERIALS AND METHODS: A 58-year-old woman came to the University
      Centre of Tropical Medicine in Gdynia after returning from a tourist journey to
      Brazil because of fever up to 39 degrees C and malaise. She had lived in South
      America many years and then moved to Europe 3 years before hospitalisation. On
      admission physical examination revealed fever, dry mucosa, moderate hypotension
      and tachycardia. In the laboratory test results, leukopoenia, thrombocytopoenia
      and elevated transaminases were observed. On the second day of the
      hospitalisation, the patient reported epigastric pain, clinical examination
      revealed tenderness of the abdomen and macular rash on the skin of the trunk and
      thighs. The ultrasonography revealed an enlarged gallbladder with thickened
      walls, with hypoechogenic area surrounding it, a dilated common biliary duct of
      heterogenic echo, and some free fluid in the peritoneal cavity. An exploratory
      laparotomy was performed after 24 h because of the persisting strong abdominal
      pain and high fever. Intraoperatively, enlarged mesenteric lymph nodes were
      found, with no symptoms of gallbladder pathology. The postoperative course was
      uncomplicated and the positive result of immunochromatographic assay for dengue
      was obtained. RESULTS: The acalculous cholecystitis has been described in the
      course of various diseases and conditions. The typical symptoms include pain in
      the right hypochondriac region, fever, positive Murphy's sign, and abnormal liver
      function tests, which were observed in the presented case. Cholecystectomy is not
      usually indicated in the course of dengue (typically a self-limiting disease) due
      to a high risk of bleeding. CONCLUSIONS: The case provides a rationale for the
      inclusion of acalculous cholecystitis in the differential diagnosis in patients
      with abdominal pain returning from dengue endemic areas.

PMID- 27029929
TI  - HIV/AIDS, health and wellbeing study among International Transport Workers'
      Federation (ITF) seafarer affiliates.
AB  - BACKGROUND: Transport workers generally face a higher-than-average risk of HIV as
      well as other health challenges. In order to improve understanding of health
      issues in the maritime sector, including but not limited to HIV/AIDS, and to
      prepare appropriate responses the International Transport Workers' Federation
      (ITF) conducted a study of the views and needs of those affiliates. MATERIALS AND
      METHODS: The ITF carried out two surveys. The first consisted of a questionnaire
      sent to all ITF seafarer affiliates to establish their concerns about health
      issues, including the impact of HIV/AIDS, and to assess the extent and nature of
      existing trade union programmes. The second consisted of a knowledge, attitude
      and behaviour survey on health, wellbeing and AIDS among a cross-section of
      individual members administered through anonymous and confidential questionnaires
      by maritime affiliates in four countries in different regions and an identical
      online questionnaire through Survey Monkey. RESULTS: For the first survey,
      replies were received from 35 unions in 30 countries, including major seafarer
      supplying countries - India, Indonesia, Myanmar, Philippines, Turkey, Ukraine -
      and major beneficial ownership countries such as Germany, Italy, Norway, and
      South Korea. Health issues of concern included HIV and other sexually transmitted
      infections for over three-quarters of them, and then alcohol use, weight control,
      and mental health. All said they would welcome ITF support in starting or
      strengthening a programme on general health and/or HIV. Replies were received to
      the second survey from 615 individual seafarers. Half to three-quarters said they
      worried about their weight, lack of exercise and drinking; over half felt
      depressed sometimes or often. There were serious knowledge gaps in a number of
      areas, especially HIV transmission and prevention, as well as high levels of
      stigma towards workmates with HIV. CONCLUSIONS: A number of health issues and
      information gaps remain unaddressed on board and pre-departure. Mental health is
      especially neglected but the needs emerge clearly. Seafarers believe that
      companies should provide programmes but also look to their unions for health
      information and services. The ITF has an important role to play in supporting
      affiliated unions in developing activities and in providing technical and
      strategic guidance.

PMID- 27029930
TI  - International Maritime Health Association (IMHA) - expanding participation,
      coverage and service.

PMID- 27029931
TI  - Is there any gambling disorder among mariners?

PMID- 27029932
TI  - The Centro Internazionale Radio Medico Symposium "The Way Forward of Maritime
      Telemedicine".

PMID- 27029933
TI  - Comparison of the Orbscan II topographer and the iTrace aberrometer for the
      measurements of keratometry and corneal diameter in myopic patients.
AB  - BACKGROUND: The purpose of this study was to compare corneal power and horizontal
      corneal diameter (white-to-white [WTW] distance) readings obtained by the Orbscan
      II topographer and the iTrace aberrometer. METHODS: Keratometry readings in the
      flat (Kf) and steep (Ks) meridians and WTW distance were measured with the
      Orbscan II and iTrace systems in 100 myopic patients. Statistical evaluation was
      performed using the paired t test, Pearson correlation, and Bland-Altman analysis
      for comparison of measurement techniques. RESULTS: The mean keratometry values
      with the Orbscan II and iTrace were 43.16 +/- 1.44 and 42.64 +/- 1.43 diopter
      (D), respectively (P < 0.0001). The mean WTW distance measurements with the
      Orbscan II and iTrace were 11.57 +/- 0.34 and 11.33 +/- 0.36 mm, respectively (P
      < 0.0001). For the measurement of corneal power, the 95 % limits of agreement
      (LoA) between the Orbscan II and iTrace were - 0.21 to 1.21 D for the flat
      meridian and - 0.15 to 1.25 D for the steep meridian. For the measurement of WTW
      distance, the range of the 95 % LoA between the two devices was 0.47 mm.
      CONCLUSIONS: For some clinical applications, the keratometry and WTW distance
      measurements obtained by the Orbscan II topographer and the iTrace aberrometer
      differed greatly and therefore were not interchangeable. TRIAL REGISTRATION:
      Clinical trials number: ChiCTR-OCS-14005077 (August 2nd, 2014).

PMID- 27029934
TI  - Regulatory Role of miR-203 in Occurrence and Progression of Kazakh Esophageal
      squamous cell carcinoma.
AB  - Esophageal carcinoma is one of the most common malignant tumors and the Kazakh
      national minority (ethnic) in Xinjiang (northwest of China) has been reported to
      be one of the highest incidence of Esophageal squamous cell carcinoma (ESCC) in
      the world. MicroRNA-203 (miR-203) was described as a tumor-suppressive miRNA in
      several cancers, but little study about the role of miR-203 in Kazakh ESCC.
      Therefore, we aimed to investigate the role of miR-203 in the occurrence and
      progression of Kazakh ESCC. Quantitative real-time polymerase chain reaction (qRT
      PCR) was used to detect miR-203 expression, and immunohistochemistry (IHC) was
      used to examine P63 expression. The expression level of miR-203 in ESCC was
      significantly lower than that of cancer adjacent normal (CAN) samples (P < 0.05).
      Whereas the expression level of P63 in ESCC was significantly higher than that of
      CAN samples (P < 0.05), an inverse association between the expression of P63 and
      miR-203 was found but was not statistically significant (P > 0.05). These
      findings suggest that miR-203 is a tumor suppressor gene that plays an important
      role in inhibiting the occurrence of Kazakh ESCC in Xinjiang, China. 

PMID- 27029935
TI  - Clinical evaluation of a biomechanical guidance system for periacetabular
      osteotomy.
AB  - BACKGROUND: Populations suffering from developmental dysplasia of the hip
      typically have reduced femoral coverage and experience joint pain while walking.
      Periacetabular osteotomy (PAO) is one surgical solution that realigns the
      acetabular fragment. This challenging surgery has a steep learning curve.
      Existing navigation systems for computer-assisted PAO neither track the released
      fragment nor offer the means to assess fragment location. An intraoperative
      workstation--the biomechanical guidance system (BGS)--developed for PAO
      incorporates intraoperative fragment tracking and acetabular characterization
      through radiographic angles and joint biomechanics. In this paper, we investigate
      the accuracy and effectiveness of the BGS for bone fragment tracking and
      acetabular characterization in clinical settings as compared to conventional
      techniques and postoperative assessments. We also report the issues encountered
      and our remedies when using the BGS in the clinical setting. METHODS: Eleven
      consecutive patients (aged 22-48, mean 34, years) underwent 12 PAO surgeries (one
      bilateral surgery) where the BGS collected information on acetabular positioning.
      These measurements were compared with postoperative CT data and manual
      measurements made intraoperatively. RESULTS: No complications were reported
      during surgery, with surgical time-95-210 (mean 175) minutes-comparable to
      reported data for the conventional approach. The BGS-measured acetabular
      positioning showed strong agreement with postoperative CT measurements (-0.3-9.2,
      mean 3.7, degrees), whereas larger differences occurred between the surgeon's
      intraoperative manual measurements and postoperative CT measurements (-2.8-21.3,
      mean 10.5, degrees). CONCLUSIONS: The BGS successfully tracked the acetabular
      fragment in a clinical environment without introducing complications to the
      surgical workflow. Accurate 3D positioning of the acetabulum may provide more
      information intraoperatively (e.g., anatomical angles and biomechanics) without
      adversely impacting the surgery to better understand potential patient outcomes.

PMID- 27029937
TI  - Cross-classified occupational exposure data.
AB  - We demonstrate the regression analysis of exposure determinants using cross
      classified random effects in the context of lead exposures resulting from
      blasting surfaces in advance of painting. We had three specific objectives for
      analysis of the lead data, and observed: (1) high within-worker variability in
      personal lead exposures, explaining 79% of variability; (2) that the lead
      concentration outside of half-mask respirators was 2.4-fold higher than inside
      supplied-air blasting helmets, suggesting that the exposure reduction by blasting
      helmets may be lower than expected by the Assigned Protection Factor; and (3)
      that lead concentrations at fixed area locations in containment were not
      associated with personal lead exposures. In addition, we found that, on average,
      lead exposures among workers performing blasting and other activities was 40%
      lower than among workers performing only blasting. In the process of obtaining
      these analyses objectives, we determined that the data were non-hierarchical:
      repeated exposure measurements were collected for a worker while the worker was a
      member of several groups, or cross-classified among groups. Since the worker is a
      member of multiple groups, the exposure data do not adhere to the traditionally
      assumed hierarchical structure. Forcing a hierarchical structure on these data
      led to similar within-group and between-group variability, but decreased
      precision in the estimate of effect of work activity on lead exposure. We hope
      hygienists and exposure assessors will consider non-hierarchical models in the
      design and analysis of exposure assessments.

PMID- 27029936
TI  - Evidence-based green algal genomics reveals marine diversity and ancestral
      characteristics of land plants.
AB  - BACKGROUND: Prasinophytes are widespread marine green algae that are related to
      plants. Cellular abundance of the prasinophyte Micromonas has reportedly
      increased in the Arctic due to climate-induced changes. Thus, studies of these
      unicellular eukaryotes are important for marine ecology and for understanding
      Viridiplantae evolution and diversification. RESULTS: We generated evidence-based
      Micromonas gene models using proteomics and RNA-Seq to improve prasinophyte
      genomic resources. First, sequences of four chromosomes in the 22 Mb Micromonas
      pusilla (CCMP1545) genome were finished. Comparison with the finished 21 Mb
      genome of Micromonas commoda (RCC299; named herein) shows they share <=8,141 of
      ~10,000 protein-encoding genes, depending on the analysis method. Unlike RCC299
      and other sequenced eukaryotes, CCMP1545 has two abundant repetitive intron types
      and a high percent (26 %) GC splice donors. Micromonas has more genus-specific
      protein families (19 %) than other genome sequenced prasinophytes (11 %).
      Comparative analyses using predicted proteomes from other prasinophytes reveal
      proteins likely related to scale formation and ancestral photosynthesis. Our
      studies also indicate that peptidoglycan (PG) biosynthesis enzymes have been lost
      in multiple independent events in select prasinophytes and plants. However,
      CCMP1545, polar Micromonas CCMP2099 and prasinophytes from other classes retain
      the entire PG pathway, like moss and glaucophyte algae. Surprisingly, multiple
      vascular plants also have the PG pathway, except the Penicillin-Binding Protein,
      and share a unique bi-domain protein potentially associated with the pathway.
      Alongside Micromonas experiments using antibiotics that halt bacterial PG
      biosynthesis, the findings highlight unrecognized phylogenetic complexity in PG
      pathway retention and implicate a role in chloroplast structure or division in
      several extant Viridiplantae lineages. CONCLUSIONS: Extensive differences in gene
      loss and architecture between related prasinophytes underscore their divergence.
      PG biosynthesis genes from the cyanobacterial endosymbiont that became the
      plastid, have been selectively retained in multiple plants and algae, implying a
      biological function. Our studies provide robust genomic resources for emerging
      model algae, advancing knowledge of marine phytoplankton and plant evolution.

PMID- 27029938
TI  - The efficacy of early initiated, supervised, progressive resistance training
      compared to unsupervised, home-based exercise after unicompartmental knee
      arthroplasty: a single-blinded randomized controlled trial.
AB  - OBJECTIVE: To examine if supervised progressive resistance training was superior
      to home-based exercise in rehabilitation after unicompartmental knee
      arthroplasty. DESIGN: Single blinded, randomized clinical trial. SETTING:
      Surgery, progressive resistance training and testing was carried out at Aarhus
      University Hospital and home-based exercise was carried out in the home of the
      patient. SUBJECTS: Fifty five patients were randomized to either progressive
      resistance training or home-based exercise. INTERVENTION: Patients were
      randomized to either progressive resistance training (home based exercise five
      days/week and progressive resistance training two days/week) or control group
      (home based exercise seven days/week). MAIN MEASURES: Preoperative assessment, 10
      week (primary endpoint) and one-year follow-up were performed for leg extension
      power, spatiotemporal gait parameters and knee injury and osteoarthritis outcome
      score (KOOS). RESULTS: Forty patients (73%) completed 1-year follow-up. Patients
      in the progressive resistance training group participated in average 11 of 16
      training sessions. Leg extension power increased from baseline to 10-week follow
      up in progressive resistance training group (progressive resistance training:
      0.28 W/kg, P= 0.01, control group: 0.01 W/kg, P=0.93) with no between-group
      difference. Walking speed and KOOS scores increased from baseline to 10-week
      follow-up in both groups with no between-group difference (six minutes walk test
      P=0.63, KOOS P>0.29). CONCLUSIONS: Progressive resistance training two days/week
      combined with home based exercise five days/week was not superior to home based
      exercise seven days/week in improving leg extension power of the operated leg.

PMID- 27029939
TI  - A low cost virtual reality system for home based rehabilitation of the arm
      following stroke: a randomised controlled feasibility trial.
AB  - OBJECTIVE: To assess the feasibility of conducting a randomised controlled trial
      of a home-based virtual reality system for rehabilitation of the arm following
      stroke. DESIGN: Two group feasibility randomised controlled trial of intervention
      versus usual care. SETTING: Patients' homes. PARTICIPANTS: Patients aged 18 or
      over, with residual arm dysfunction following stroke and no longer receiving any
      other intensive rehabilitation. INTERVENTIONS: Eight weeks' use of a low cost
      home-based virtual reality system employing infra-red capture to translate the
      position of the hand into game play or usual care. MAIN MEASURES: The primary
      objective was to collect information on the feasibility of a trial, including
      recruitment, collection of outcome measures and staff support required. Patients
      were assessed at three time points using the Wolf Motor Function Test, Nine-Hole
      Peg Test, Motor Activity Log and Nottingham Extended Activities of Daily Living.
      RESULTS: Over 15 months only 47 people were referred to the team. Twenty seven
      were randomised and 18 (67%) of those completed final outcome measures. Sample
      size calculation based on data from the Wolf Motor Function Test indicated a
      requirement for 38 per group. There was a significantly greater change from
      baseline in the intervention group on midpoint Wolf Grip strength and two
      subscales of the final Motor Activity Log. Training in the use of the equipment
      took a median of 230 minutes per patient. CONCLUSIONS: To achieve the required
      sample size, a definitive home-based trial would require additional strategies to
      boost recruitment rates and adequate resources for patient support.

PMID- 27029940
TI  - In Rwandese Women with Low Iron Status, Iron Absorption from Low-Phytic Acid
      Beans and Biofortified Beans Is Comparable, but Low-Phytic Acid Beans Cause
      Adverse Gastrointestinal Symptoms.
AB  - BACKGROUND: Phytic acid (PA) is a major inhibitor of iron bioavailability from
      beans, and high PA concentrations might limit the positive effect of biofortified
      beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase
      iron bioavailability. OBJECTIVE: We set out to test whether lpa beans provide
      more bioavailable iron than a BB variety when served as part of a composite meal
      in a bean-consuming population with low iron status. METHODS: Dietary iron
      absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and
      PA concentrations) was compared in 25 nonpregnant young women with low iron
      status with the use of a multiple-meal crossover design. Iron absorption was
      measured with stable iron isotopes. RESULTS: PA concentration in lpa beans was
      ~10% of BBs and CBs, and iron concentration in BBs was ~2- and 1.5-fold compared
      with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans
      [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0%
      (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron
      absorbed from lpa beans and BBs was 421 MUg (95% CI: 234, 756 MUg) and 431 MUg
      (95% CI: 237, 786 MUg), respectively, and did not significantly differ, but was
      >50% higher (P < 0.005) than from CBs (278 MUg; 95% CI: 150, 499 MUg). In our
      trial, the lpa beans were hard to cook, and their consumption caused transient
      adverse digestive side effects in ~95% of participants. Gel electrophoresis
      analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans.
      CONCLUSION: BBs and lpa beans provided more bioavailable iron than control beans
      and could reduce dietary iron deficiency. Digestive side effects of lpa beans
      were likely caused by PHA-L, but it is unclear to what extent the associated
      digestive problems reduced iron bioavailability. This trial was registered at
      clinicaltrials.gov as NCT02215278.

PMID- 27029941
TI  - Glycine Regulates Expression and Distribution of Claudin-7 and ZO-3 Proteins in
      Intestinal Porcine Epithelial Cells.
AB  - BACKGROUND: Glycine traditionally is classified as a nutritionally nonessential
      amino acid in humans and animals. Because of its abundance in the body and its
      extensive use via multiple pathways, requirements for glycine are particularly
      high in neonates. Our recent studies show that dietary glycine supplementation is
      needed for optimal intestinal development in piglets. Importantly, reduced
      concentrations of glycine in the lumen of the small intestine are associated with
      gut dysfunction in low-birth-weight piglets. However, the mechanisms responsible
      for the beneficial effects of glycine on the intestinal mucosal barrier are
      largely unknown. OBJECTIVE: This study tested the hypothesis that glycine may
      regulate the expression and distribution of tight junction (TJ) proteins, thereby
      contributing to intestinal mucosal barrier function. METHODS: Enterocytes
      isolated from the jejunum of a healthy newborn pig were propagated to establish a
      stable cell line. The cells were cultured with 0.05 mmol glycine/L (control;
      concentration in the small intestinal lumen of low-birth-weight piglets) or 0.25
      or 1.0 mmol glycine/L for the indicated periods of time. Epithelial barrier
      integrity and expression and localization of TJ proteins were analyzed by using
      monolayer transepithelial electrical resistance (TEER) and paracellular
      permeability, Western blot, and immunofluorescence imaging. RESULTS: Compared
      with controls, cells cultured with 0.25 or 1.0 mmol glycine/L increased TEER (P <
      0.05) by 46-53% and 80-111%, respectively, at 60-72 h. Correspondingly,
      paracellular permeability was reduced (P < 0.05) by 6-21% and 18-27% for 0.25 or
      1.0 mmol glycine/L treatment, respectively, at 36-72 h. Compared with controls,
      protein abundances for claudin-3, claudin-7, and zonula occludens (ZO) 3 were
      enhanced (25-33%, P < 0.05) by 0.25 and 1.0 mmol glycine/L at 8 h, whereas those
      for occludin, claudin-1, claudin-4, and ZO-2 were not affected. Compared with
      controls, 1.0 mmol glycine/L reduced the protein abundance of ZO-1 by 20% at 8 h
      (P < 0.05), but 0.25 mmol glycine/L had no effect. A glycine concentration of
      0.25 mmol/L sustained the localization of claudin-7 and ZO-3 to the interface
      between enterocytes. Interestingly, 1 mmol glycine/L promoted the distribution of
      claudin-4 and claudin-7 to the cytosol and nucleus, and the localization of ZO-3
      to the plasma membranes, while decreasing the distribution of ZO-1 at cell-cell
      contact sites, compared with control cells. CONCLUSION: Physiologic
      concentrations of glycine support intestinal mucosal barrier function by
      regulating the abundance and distribution of claudin-7 and ZO-3 in enterocytes.
      Supplementation with glycine may provide an effective nutritional strategy to
      improve intestinal integrity in piglets.

PMID- 27029942
TI  - Oncotarget Strategies For Herpes Simplex Virus-1.
AB  - The high level of manipulability of viral genome has set up HSV-1 to be an ideal
      viral vector for oncolytic virotherapy. In the past two decades, several
      oncolytic HSV-1 viruses have been successfully developed and assessed in animal
      studies. Accumulated evidences show that oncolytic HSV- 1 can efficiently infect
      many tumor cells and augment anti-tumor effect by induction of systemic innate
      and adaptive immune responses. Inspiring results have been accomplished in
      several phase I clinical trials for glioma, head and neck squeous cells carcinoma
      and Melanoma using oncolytic HSV- 1 viruses. More recently, oncovey, one of
      oncolytic HSV-1 viruses has been approved by FDA for the comprehensive evolution
      of its anti-tumor effects in phase III clinical trials. These promising studies
      encourage more efforts to be devoted to craft the new generation of oncolytic HSV
      1. Herein, we will review and summarize the basic strategies to construct
      oncolytic HSV-1 viruses and their applications in cancer therapy. 

PMID- 27029944
TI  - Thermal Assisted In Vivo Gene Electrotransfer.
AB  - Gene electrotransfer is an effective approach for delivering plasmid DNA to a
      variety of tissues. Delivery of molecules with electric pulses requires control
      of the electrical parameters to achieve effective delivery. Since discomfort or
      tissue damage may occur with high applied voltage, the reduction of the applied
      voltage while achieving the desired expression may be an important improvement.
      One possible approach is to combine electrotransfer with exogenously applied
      heat. Previous work performed in vitro demonstrated that increasing temperature
      before pulsing can enhance gene expression and made it possible to reduce
      electric fields while maintaining expression levels. In the study reported here,
      this combination was evaluated in vivo using a novel electrode device designed
      with an inserted laser for application of heat. The results obtained in this
      study demonstrated that increased temperature during electrotransfer increased
      expression or maintained expression with a reduction in applied voltage. With
      further optimization this approach may provide the basis for both a novel method
      and a novel instrument that may greatly enhance translation of gene
      electrotransfer. 

PMID- 27029945
TI  - Visualization of Nonspecific Antitumor Effectiveness and Vascular Effects of Gene
      Electro-Transfer to Tumors.
AB  - BACKGROUND: Gene Electro Transfer (GET) is a promising method for therapeutic
      purposes. Intratumoral GET has reached clinical evaluation for antitumor
      treatment. An increasing number of studies suggests that antitumor effectiveness
      not only depends on the transfection efficiency, but also on the induction of
      immune responses and vascular effects that result in the nonspecific induction of
      cell death. Real time noninvasive optical imaging methods allow longitudinal
      studies of these dynamic biological processes. OBJECTIVE: In the present study, a
      noninvasive bioluminescence technology was used to further explore the phenomena
      associated with GET to tumors by a real time monitoring of the transfection
      efficiency as well as cell death following the treatment. METHOD: By using
      transgenic light-producing tumors, tumor growth was visualized, and since dead
      cells stop producing light, effectiveness of the treatment or the emergence of
      necrotic areas in the tumors was followed visually. The transfection efficiency
      of reporter genes (iRFP protein and luciferase) in the subcutaneous tumors was
      also evaluated. RESULTS: Our results showed that the GET of a reporter gene can
      lead to nonspecific antitumor effectiveness and even complete regression of
      tumors. Using light-producing tumors, we were also able to indirectly visualize
      the previously described vascular effects of electroporation. Additionally, using
      the intratumoral GET of a luciferase encoding plasmid, we localized the source of
      the expression mainly in the peritumoral and not in the tumoral region.
      CONCLUSION: The data obtained provide new insights into some of the phenomena
      associated with GET to tumors, which should be taken into account when designing
      improved and more effective cancer gene therapy, in order to accelerate the
      transfer of the technology into clinical trials.

PMID- 27029946
TI  - Administration of DNA Plasmid Coding Protein Aggregating Domain Induces
      Inflammatory Bone Loss.
AB  - BACKGROUND: Plasmids coding protein aggregation polypeptides from different
      sources have been proposed as genetic adjuvants for DNA vaccines. We reported
      that a plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A
      (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor
      Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of
      insoluble intracellular aggregates and subsequent cell death. OBJECTIVE: In the
      present study we addressed the question of whether there is any substantial
      immunotoxicity associated with the use of self-aggregating proteins as genetic
      adjuvants. METHODS & RESULTS: Here we report, by mean of histology, X-ray and
      molecular examinations of bone specimens, the unexpected finding that
      intramuscular injection of pATRex in mice triggers, per se, severe bone loss
      (osteoporosis) independently from the sex and genotype of the treated animals.
      CONCLUSION: Even though the study suggests that proteinaceous "sticky " adjuvants
      are unlikely to find their way into practical vaccination, the information gained
      is of value as ATRex injections could provide an additional, simplified, mouse
      model of osteoporosis. Moreover, our results provide experimental support to the
      hypothesis that proteotoxic aggregates chronically activate the innate immune
      system in amyloid and aggregosome associated disorders.

PMID- 27029947
TI  - Gene Electrotransfer in 3D Reconstructed Human Dermal Tissue.
AB  - Gene electrotransfer into the skin is of particular interest for the development
      of medical applications including DNA vaccination, cancer treatment, wound
      healing or treatment of local skin disorders. However, such clinical applications
      are currently limited due to poor understanding of the mechanisms governing DNA
      electrotransfer within human tissue. Nowadays, most studies are carried out in
      rodent models but rodent skin varies from human skin in terms of cell composition
      and architecture. We used a tissue-engineering approach to study gene
      electrotransfer mechanisms in a human tissue context. Primary human dermal
      fibroblasts were cultured according to the self-assembly method to produce 3D
      reconstructed human dermal tissue. In this study, we showed that cells of the
      reconstructed cutaneous tissue were efficiently electropermeabilized by applying
      millisecond electric pulses, without affecting their viability. A reporter gene
      was successfully electrotransferred into this human tissue and gene expression
      was detected for up to 48h. Interestingly, the transfected cells were solely
      located on the upper surface of the tissue, where they were in close contact with
      plasmid DNA solution. Furthermore, we report evidences that electrotransfection
      success depends on plasmid mobility within tissue- rich in collagens, but not on
      cell proliferation status. In conclusion, in addition to proposing a reliable
      alternative to animal experiments, tissue engineering produces valid biological
      tool for the in vitro study of gene electrotransfer mechanisms in human tissue. 

PMID- 27029943
TI  - Gene Electrotransfer: A Mechanistic Perspective.
AB  - Gene electrotransfer is a powerful method of DNA delivery offering several
      medical applications, among the most promising of which are DNA vaccination and
      gene therapy for cancer treatment. Electroporation entails the application of
      electric fields to cells which then experience a local and transient change of
      membrane permeability. Although gene electrotransfer has been extensively studied
      in in vitro and in vivo environments, the mechanisms by which DNA enters and
      navigates through cells are not fully understood. Here we present a comprehensive
      review of the body of knowledge concerning gene electrotransfer that has been
      accumulated over the last three decades. For that purpose, after briefly
      reviewing the medical applications that gene electrotransfer can provide, we
      outline membrane electropermeabilization, a key process for the delivery of DNA
      and smaller molecules. Since gene electrotransfer is a multipart process, we
      proceed our review in describing step by step our current understanding, with
      particular emphasis on DNA internalization and intracellular trafficking.
      Finally, we turn our attention to in vivo testing and methodology for gene
      electrotransfer. 

PMID- 27029949
TI  - A computational simulation of the effect of hybrid treatment for thoracoabdominal
      aortic aneurysm on the hemodynamics of abdominal aorta.
AB  - Hybrid visceral-renal debranching procedures with endovascular repair have been
      proposed as an appealing technique to treat conventional thoracoabdominal aortic
      aneurysm (TAAA). This approach, however, still remained controversial because of
      the non-physiological blood flow direction of its retrograde visceral
      revascularization (RVR) which is generally constructed from the aortic
      bifurcation or common iliac artery. The current study carried out the numerical
      simulation to investigate the effect of RVR on the hemodynamics of abdominal
      aorta. The results indicated that the inflow sites for the RVR have great impact
      on the hemodynamic performance. When RVR was from the distal aorta, the perfusion
      to visceral organs were adequate but the flow flux to the iliac artery
      significantly decreased and a complex disturbed flow field developed at the
      distal aorta, which endangered the aorta at high risk of aneurysm development.
      When RVR was from the right iliac artery, the abdominal aorta was not troubled
      with low WSS or disturbed flow, but the inadequate perfusion to the visceral
      organs reached up to 40% and low WSS and flow velocity predominated appeared at
      the right iliac artery and the grafts, which may result in the stenosis in grafts
      and aneurysm growth on the host iliac artery. 

PMID- 27029950
TI  - The effects of self-management intervention among middle-age adults with knee
      osteoarthritis.
AB  - AIM: The aim of this study was to explore the effects of a self-management
      intervention for middle-aged adults with knee osteoarthritis. BACKGROUND: Knee
      osteoarthritis is a common cause of lower limb disability in middle-aged and
      older adults. Use of self-management interventions that apply the self-regulation
      theory have not been reported for patients with knee osteoarthritis. DESIGN: A
      quasi-experimental design was applied. METHODS: Knee osteoarthritis patients were
      recruited from two medical centres in northern Taiwan by convenience sampling
      between July 2013-May 2014. We developed a self-management intervention programme
      for knee osteoarthritis; participants began an individualized programme 4 weeks
      after recruitment. Effectiveness of the intervention was evaluated using the Knee
      Injury and Osteoarthritis Outcome Score, Health Care Questionnaire and the Short
      Form Health Survey. A generalized estimating equation compared assessment scores
      for 105 participants after the intervention (10 and 18 weeks) with scores at 4
      weeks. RESULTS: Knee symptoms and physical function scores significantly improved
      and quality-of-life scores significantly increased while body mass index,
      unplanned medical consultations and doses of pain medication significantly
      decreased at 10 and 18 weeks compared with 4 weeks. After adjusting for the
      effect of time- and significant-related factors, knee symptoms and physical
      function, body mass index and quality of life significantly improved at 10 and 18
      weeks compared with 4 weeks. CONCLUSIONS: The self-management intervention based
      on self-regulation theory, improved participants' symptoms and functions of knee
      osteoarthritis, overall health and quality of life. Offering self-management
      interventions in clinical practice can be beneficial for patients with knee
      osteoarthritis.

PMID- 27029951
TI  - Mephedrone and 3,4-Methylenedioxypyrovalerone (MDPV): Synthetic Cathinones With
      Serious Health Implications.
AB  - This article presents information on the predominant synthetic cathinones used in
      the Western world, mephedrone and methylenedioxypyrovalerone (MDPV). Synthetic
      cathinones are commonly used drugs of abuse in the United States and Europe, with
      numerous cases of patient harm and death. Patients exhibit many neurological,
      cardiovascular, and muscular adverse events and frequently require therapy to
      control psychotic or agitated states and acute kidney injury resulting from
      myopathy or rhabdomyolysis. There are potential genetic polymorphisms and drug
      interactions that might accentuate risk, but there are no studies evaluating to
      what extent this occurs or if it is clinically relevant. Clinicians should be
      aware of the known pharmacology, pharmacokinetics, and reports of effects to
      detect potential issues and treat patients presenting with these adverse effects.

PMID- 27029948
TI  - Prospective purification of perivascular presumptive mesenchymal stem cells from
      human adipose tissue: process optimization and cell population metrics across a
      large cohort of diverse demographics.
AB  - BACKGROUND: Adipose tissue is an attractive source of mesenchymal stem cells
      (MSC) as it is largely dispensable and readily accessible through minimally
      invasive procedures such as liposuction. Until recently MSC could only be
      isolated in a process involving ex-vivo culture and their in-vivo identity,
      location and frequency remained elusive. We have documented that pericytes (CD45
      , CD146+, and CD34-) and adventitial cells (CD45-, CD146-, CD34+) (collectively
      termed perivascular stem cells or PSC) represent native ancestors of the MSC, and
      can be prospectively purified using fluorescence activated cell sorting (FACS).
      In this study we describe an optimized protocol that aims to deliver pure, viable
      and consistent yields of PSC from adipose tissue. We analysed the frequency of
      PSC within adipose tissue, and the effect of patient and procedure based
      variables on this yield. METHODS: Within this twin centre study we analysed the
      adipose tissue of n = 131 donors using flow cytometry to determine the frequency
      of PSC and correlate this with demographic and processing data such as age, sex,
      BMI and cold storage time of the tissue. RESULTS: The mean number of stromal
      vascular fraction (SVF) cells from 100 ml of lipoaspirate was 34.4 million.
      Within the SVF, mean cell viability was 83 %, with 31.6 % of cells being
      haematopoietic (CD45+). Adventitial cells and pericytes represented 33.0 % and 8
      % of SVF cells respectively. Therefore, a 200 ml lipoaspirate would theoretically
      yield 23.2 million viable prospectively purified PSC - sufficient for many
      reconstructive and regenerative applications. Minimal changes were observed in
      respect to age, sex and BMI suggesting universal potential application.
      CONCLUSIONS: Adipose tissue contains two anatomically and phenotypically discreet
      populations of MSC precursors - adventitial cells and pericytes - together
      referred to as perivascular stem cells (PSC). More than 9 million PSC per 100 ml
      of lipoaspirate can be rapidly purified to homogeneity using flow cytometry in
      clinically relevant numbers potentially circumventing the need for purification
      and expansion by culture prior to clinical use. The number and viability of PSC
      are minimally affected by patient age, sex, BMI or the storage time of the
      tissue, but the quality and consistency of yield can be significantly influenced
      by procedure based variables.

PMID- 27029952
TI  - Allosteric inhibition of c-Met kinase in sub-microsecond molecular dynamics
      simulations induced by its inhibitor, tivantinib.
AB  - Protein dynamics in the allosteric regulation of enzymes is crucial for
      understanding the regulation mechanism of enzymes and designing of inhibitors.
      Kinases have a conserved Asp-Phe-Gly motif (DFG motif) whose conformation
      determines the activation state of the kinase; however, knowledge on
      conformational transition of the DFG motif from the active state to the inactive
      state ("DFG-flip") is quite limited. Here we report a DFG-flip of c-Met kinase in
      molecular dynamics (MD) simulations, induced by its allosteric inhibitor
      tivantinib. Our MD simulations showed that, with the assistance of tivantinib, c
      Met may transit from the DFG-in state to the DFG-out state in a sub-microsecond
      time-scale. A unique binding mode of tivantinib to c-Met was identified to be the
      key intermediate for the ligand-induced DFG-flip. This study provides a detailed
      process of inhibitor-induced kinase allostery, as well as important insights into
      the DFG-flip mechanism and the design of allosteric inhibitors, not only of c
      Met, but also of other kinases. 

PMID- 27029953
TI  - Arterial Stiffness and Central Hemodynamics in Thyroidectomized Patients on Long
      Term Substitution Therapy with Levothyroxine.
AB  - BACKGROUND: Long-term levothyroxine (LT4) therapy targeting thyrotropin (TSH)
      suppression in hypothyroid patients treated for thyroid cancer has been
      associated with increased arterial stiffness and increased cardiovascular
      mortality. However, most patients with hypothyroidism receive LT4 therapy
      targeting TSH in the reference range. The long-term vascular effects of this
      strategy have never been evaluated. METHODS: Arterial stiffness and central
      hemodynamics were studied in 30 thyroidectomized patients (Mage = 54.5 +/- 10.2
      years; 80% female) on long-term (median = 11 years; range 3-41 years) LT4
      replacement therapy targeting TSH in the reference range and 30 sex- and age
      matched controls. Arterial stiffness was evaluated by carotid-femoral pulse wave
      velocity (PWV) and central hemodynamics by pulse wave analysis using the
      SphygmoCor system. RESULTS: TSH levels were comparable in patients and controls
      (median = 1.99 * 10(3) IU/L [range 0.24-5.64 * 10(3) IU/L] vs. median = 2.13 *
      10(3) IU/L [range 0.59-5.63 * 10(3) IU/L]; p = 0.69), but patients had higher
      plasma thyroxine and lower plasma triiodothyronine levels than controls (median =
      108 nmol/L [range 84-149 nmol/L] vs. 86 nmol/L [range 59-141 nmol/L]; p < 0.001
      and median = 1.49 nmol/L [range 1.00-2.37 nmol/L] vs. 1.62 nmol/L [range 1.18
      2.09 nmol/L]; p = 0.04, respectively). PWV was not significantly higher in
      patients compared to controls (8.2 +/- 1.9 vs. 7.9 +/- 1.9 m/s, p = 0.69).
      Similarly, no group differences were observed in central systolic/diastolic blood
      pressure (120 +/- 16 mmHg vs. 119 +/- 12 mmHg, p = 0.77; and 80 +/- 11 mmHg vs.
      80 +/- 10 mmHg, p = 0.98, respectively), the augmentation index (28 +/- 13% vs.
      29 +/- 8%, p = 0.72), or the pulse pressure amplification ratio (129 +/- 17% vs.
      124 +/- 13%, p = 0.18). CONCLUSION: Despite subtle differences in plasma levels
      of thyroid hormones, long-term LT4 replacement therapy targeting TSH in the
      reference range does not seem to cause adverse effects on arterial stiffness and
      central hemodynamics.

PMID- 27029954
TI  - Unprecedented Carbonato Intermediates in Cyclic Carbonate Synthesis Catalysed by
      Bimetallic Aluminium(Salen) Complexes.
AB  - The mechanism by which [Al(salen)]2 O complexes catalyse the synthesis of cyclic
      carbonates from epoxides and carbon dioxide in the absence of a halide cocatalyst
      has been investigated. Density functional theory (DFT) studies, mass spectrometry
      and (1) H NMR, (13) C NMR and infrared spectroscopies provide evidence for the
      formation of an unprecedented carbonato bridged bimetallic aluminium complex
      which is shown to be a key intermediate for the halide-free synthesis of cyclic
      carbonates from epoxides and carbon dioxide. Deuterated and enantiomerically-pure
      epoxides were used to study the reaction pathway. Based on the experimental and
      theoretical results, a catalytic cycle is proposed.

PMID- 27029955
TI  - Interface failure modes explain non-monotonic size-dependent mechanical
      properties in bioinspired nanolaminates.
AB  - Bioinspired discontinuous nanolaminate design becomes an efficient way to
      mitigate the strength-ductility tradeoff in brittle materials via arresting the
      crack at the interface followed by controllable interface failure. The analytical
      solution and numerical simulation based on the nonlinear shear-lag model
      indicates that propagation of the interface failure can be unstable or stable
      when the interfacial shear stress between laminae is uniform or highly localized,
      respectively. A dimensionless key parameter defined by the ratio of two
      characteristic lengths governs the transition between the two interface-failure
      modes, which can explain the non-monotonic size-dependent mechanical properties
      observed in various laminate composites. 

PMID- 27029956
TI  - The effect of quadriceps femoris muscle Kinesio Taping on physical fitness
      indices in non-injured athletes.
AB  - BACKGROUND: Evaluating the effect of kinesio taping of quadriceps femoris muscle
      on some physical fitness indices including maximal voluntary isometric
      contraction (MVIC), vertical jump, agility and sprint in healthy collegiate
      athletes. METHODS: Forty-four (23 male and 21 female) healthy collegiate athletes
      voluntarily participated in this study. The MVIC of quadriceps muscle (N) of the
      dominant leg was assessed by digital Dynamometer. vertical jump, agility and
      sprint was assessed using Sargent vertical jump, shuttle run agility and 30-yard
      sprint tests, respectively. All measures were obtained in 4 trails: control
      (without taping), two trials with 24 hours interval, immediately and 24 hours
      after tape application. Two conditions of with and without taping measures were
      performed by one week interval. Everybody was compared to themselves during
      different situations. Data was analyzed using SPSS software and ANOVA with
      repeated measure statistical test. RESULTS: MVIC, jumping and sprint performance
      significantly improved immediately and 24 hours following KT application compared
      to non KT conditions (P<0.05). Agility was improved 24 hours following taping
      (P<0.05), but KT caused no significant immediate effect on agility (P>0.05). 24
      hours KT caused significant improvement in MVIC, jumping and agility performance,
      but caused no significant effect on sprint compared to immediately following
      taping. CONCLUSIONS: KT influenced positively MVIC, jumping, agility and sprint
      and the major effect was achieved by maintaining KT for 24hours in healthy
      athletes. Although, regarding the study limitations, future studies are
      recommended for clarification.

PMID- 27029957
TI  - Effects of plyometrics performed during warm-up on 20 and 40 m sprint
      performance.
AB  - BACKGROUND: Postactivation potentiation in the form of a plyometric during warm
      ups have been shown to improve performance in some speed/power events. This study
      aimed to determine if a plyometric during warm up can increase sprint performance
      in a 20 and 40 m sprint. METHODS: In this study we measured sprint times of 10
      male track and field athletes over distances of 20 and 40 m after warm-ups with
      and without a plyometric exercise. The subjects performed the sprints at the same
      time on 2 different days, once with the experimental treatment, a plyometric
      exercise in the form of a plate jump, and once without. Plate jumps were chosen
      as the plyometric treatment because they do not require special equipment or
      facilities. The plate used for the plate jumps had a mass of 11.2 kilograms,
      which was between 12.8-16.6% of each athlete's body mass. RESULTS: Statistical
      analysis showed a decrease in sprint time when a plyometric was performed during
      the warm-up for both 20 (t-test P<0.05) and 40 m sprints (t-test P<0.01). The
      effect sizes of the improvement for both the 20 and 40 m sprints were d=0.459 and
      d=0.405, respectively, which is considered a small to medium effect. CONCLUSIONS:
      These results indicate that including a plyometric exercise during warm-ups can
      improve sprint performance in collegiate aged male sprinters during short
      sprints.

PMID- 27029958
TI  - Athletes' perception of the causes of injury in gymnastics.
AB  - BACKGROUND: Gymnastics requires a high level of flexibility, conditioning and
      complete body recruitment that is infrequently matched by other sports. Artistic
      gymnastics has a relatively high incidence of injuries, which are generally of
      minor or medium severity. With all its complexity, it poses a unique diagnostic
      and treatment challenge to medical practitioners. The present study examined
      athletes' perception of the causes of injury and of the possible ways to reduce
      their incidence. METHODS: The research involved 63 quality athletes, of whom 20
      were in men's artistic gymnastics, 21 in women's artistic gymnastics, and 22 in
      rhythmic gymnastics. We used the self-assessment method. Factors inducing injury
      were grouped into three different categories: training, the athlete himself, and
      the environment. We used the chi2 test to test the association between a risk
      factor and injuries. The association between injuries and risk factors was also
      tested using a multivariate logistic regression analysis. RESULTS: Overall, an
      incidence of 184 injuries was found, of which 67 (36.4%) were acute and 117
      (63.5%) were chronic injuries. According to binary logistic regression analyses,
      psychological factors significantly associated with the prevalence of acute and
      chronic injury in both sexes for all disciplines were: a poor technique, improper
      methods of teaching, and an inadequate load. In our study, higher rates of acute
      and chronic injury were observed among male gymnasts, who reported their
      occurrence during training by overload, and among female gymnasts, who reported a
      poor technique, improper methods of teaching, and an inadequate load as main
      causes of their occurrence. CONCLUSIONS: Improving the communication between
      athletes and coaches, taking the opinion of an athlete into account, and the
      athlete's active involvement in preparation of the program include the most
      crucial points for reducing the incidence of injuries.

PMID- 27029959
TI  - The metabolic power and energetic demands of elite Gaelic football match play.
AB  - BACKGROUND: Metabolic power has not yet been investigated within elite Gaelic
      football. The aim of the current investigation was to compare the metabolic power
      demands between positional groups and examine the temporal profile of elite
      Gaelic football match play. METHODS: Global positional satellite system (GPS)
      data were collected from 50 elite Gaelic football players from 4 inter-county
      teams during 35 elite competitive matches over a three season period. A total of
      351 complete match samples were obtained for final analysis. Players were
      categorized based on positional groups; full-back, half-back, midfield, half
      forward and full-forward. Instantaneous raw velocity data was obtained from the
      GPS and exported to a customized spreadsheet which provided estimations of both
      speed based, derived metabolic power and energy expenditure variables (total
      distance, high speed distance, average metabolic power, high power distance and
      total energy expenditure). RESULTS: Match mean distance was 9222+/-1588 m,
      reflective of an average metabolic power of 9.5-12.5 W.kg-1, with an average
      energy expenditure of 58-70 Kj.kg-1 depending on position. There were significant
      differences between positional groups for both speed-based and metabolic power
      indices. Midfielders covered more total and high-speed distance, as well as
      greater average and overall energy expenditure compared to other positions
      (P<0.001). A reduction in total, high-speed, and high-power distance, as well as
      average metabolic power throughout the match (P<0.001) was observed. CONCLUSIONS:
      Positional differences exist for both metabolic power and traditional running
      based variables. The middle three positions (midfield, half-back and half
      forward) possess greater activity profiles when compared to other positional
      groups. The reduction in metabolic power and traditional running based variables
      are comparable across match play. The current study demonstrates that metabolic
      power may contribute to our understanding of Gaelic football match-play.

PMID- 27029960
TI  - One single bout of low-intensity isometric handgrip exercise reduces blood
      pressure in healthy pre- and hypertensive individuals.
AB  - BACKGROUND: The aim of this study was to investigate the acute effect of one
      single session of isometric handgrip exercise (IHG) on blood pressure (BP) during
      daily life activities in healthy adults. METHODS: Fifteen healthy adults with pre
      or stage 1 hypertension (10 men; mean age 48+/-7.1 years) completed two
      experimental sessions in random order: one control (rest for 15 minutes) and one
      low intensity IHG session (4*2 minutes sustained contractions at 30% of maximal
      volutional contraction interspersed with 1-minute rest intervals). Blood pressure
      was recorded before each intervention and following the intervention BP was
      recorded for one hour in the office and thereafter for 6 hours during their daily
      activities by means of an ambulatory BP device. Physical activity (number of
      steps and total energy expenditure) was assessed by means of a SenseWear mini
      device. RESULTS: Systolic BP was higher the first minute after the isometric
      handgrip exercise but quickly returned to baseline levels after 15 minutes in the
      office. Over the 7-hour period, systolic blood pressure was significantly lower (
      5.4+/-7.3 vs. +0.23+/-6.9; P<0.05) after IHG compared to the control session.
      Although not significant, a tendency was observed towards a lower diastolic blood
      pressure after IHG compared to control (P=0.09). Physical activity behavior was
      similar on both days (P>0.05). CONCLUSIONS: This study demonstrates that one
      single bout of IHG can result in an overall reduction in BP during daily
      activities. More research is needed to confirm these findings and to explain
      possible mechanisms responsible for these observed changes.

PMID- 27029961
TI  - Chirality of nanophotonic waveguide with embedded quantum emitter for
      unidirectional spin transfer.
AB  - Scalable quantum technologies may be achieved by faithful conversion between
      matter qubits and photonic qubits in integrated circuit geometries. Within this
      context, quantum dots possess well-defined spin states (matter qubits), which
      couple efficiently to photons. By embedding them in nanophotonic waveguides, they
      provide a promising platform for quantum technology implementations. In this
      paper, we demonstrate that the naturally occurring electromagnetic field
      chirality that arises in nanobeam waveguides leads to unidirectional photon
      emission from quantum dot spin states, with resultant in-plane transfer of matter
      qubit information. The chiral behaviour occurs despite the non-chiral geometry
      and material of the waveguides. Using dot registration techniques, we achieve a
      quantum emitter deterministically positioned at a chiral point and realize spin
      path conversion by design. We further show that the chiral phenomena are much
      more tolerant to dot position than in standard photonic crystal waveguides,
      exhibit spin-path readout up to 95+/-5% and have potential to serve as the basis
      of spin-logic and network implementations. 

PMID- 27029962
TI  - How scientists can reduce their carbon footprint.
AB  - Cutting down on long-distance air travel is the best way to reduce the emission
      of greenhouse gases by the scientific community. 

PMID- 27029963
TI  - 3D dual-confined sulfur encapsulated in porous carbon nanosheets and wrapped with
      graphene aerogels as a cathode for advanced lithium sulfur batteries.
AB  - Although lithium-sulfur (Li-S) batteries have attracted much attention due to
      their high theoretical specific energy and low cost, their practical applications
      have been severely hindered by poor cycle life, inadequate sulfur utilization,
      and the insulating nature of sulfur. Here, we report a rationally designed Li-S
      cathode with a dual-confined configuration formed by confining sulfur in 2D
      carbon nanosheets with an abundant porous structure followed by 3D graphene
      aerogel wrapping. The porous carbon nanosheets act as the sulfur host and
      suppress the diffusion of polysulfide, while the graphene conductive networks
      anchor the sulfur-adsorbed carbon nanosheets, providing pathways for rapid
      electron/ion transport and preventing polysulfide dissolution. As a result, the
      hybrid electrode exhibits superior electrochemical performance, including a large
      reversible capacity of 1328 mA h g(-1) in the first cycle, excellent cycling
      stability (maintaining a reversible capacity of 647 mA h g(-1) at 0.2 C after 300
      cycles) with nearly 100% Coulombic efficiency, and a high rate capability of 512
      mA h g(-1) at 8 C for 30 cycles, which is among the best reported rate
      capabilities. 

PMID- 27029964
TI  - Microsatellite markers for the tramp ant, Cardiocondyla obscurior (Formicidae:
      Myrmicinae).

PMID- 27029965
TI  - Successful treatment of chronic recurrent life-threatening bleeding due to an
      acquired factor V Inhibitor with rituximab and steroids.

PMID- 27029966
TI  - Determination of catecholamines and related compounds in mouse urine using column
      switching HPLC.
AB  - We have developed an analytical method for the determination of catecholamines
      and related compounds in mouse urine by column-switching HPLC. Selective
      extraction of the catechol compounds was performed using a precolumn modified
      with phenylboronic acid, which has a pH dependent affinity for the catechol
      structures. The pretreatment buffer, which facilitated binding of the catechols
      to the precolumn, was optimized to ensure high analyte recoveries and good peak
      shapes. We found that using the same acetonitrile content in the pretreatment
      buffer and hydrophilic interaction liquid chromatography mobile phase was
      necessary to improve peak shapes. Eight catechol compounds were selectively
      extracted and separated using 100 mmol L(-1) ammonium formate/acetonitrile (20/80
      v/v, pH 8.0) for the extraction step, and 20 mmol L(-1) ammonium formate (pH
      2.5)/acetonitrile (20/80 v/v) for elution and separation. Native fluorescence of
      the separated catechol compounds was monitored, and the limits of detection,
      corresponding to a signal to noise ratio of 3, were 9-58 nmol L(-1). Five
      catechol compounds (dopamine, epinephrine, norepinephrine, 3,4
      dihydroxyphenylglycol, and 3,4-dihydroxymandelic acid) were successfully
      quantified in mouse urine. Intra- and inter-day precisions were less than 10%,
      and performance was superior to that afforded by manual sample pretreatment. 

PMID- 27029967
TI  - Are you ready for revalidation?

PMID- 27029968
TI  - Moving patients to care homes would save hospitals money.

PMID- 27029969
TI  - Life gets better for people in their seventh decade.

PMID- 27029970
TI  - Regulator seeks to dispel misconceptions about revalidation.

PMID- 27029971
TI  - Reinventing the wheel.

PMID- 27029973
TI  - Open visiting reduces the number of inpatient falls.

PMID- 27029974
TI  - Revalidation starts for first wave of nurses and midwives.

PMID- 27029978
TI  - Registrants' guide to revalidation.

PMID- 27029988
TI  - Addressing the nutritional needs of older patients.
AB  - Malnutrition affects three million people in the UK each year, 10% of whom are
      aged 65 and older. Chronic malnutrition is associated with well-documented
      clinical criteria for frailty: unintentional weight loss, weakness, immobility
      and sarcopenia. Frail, older people who are malnourished visit their GP twice as
      often as well-nourished equivalents and are three times more likely to be
      admitted to hospital where, on average, their stay is three days longer. Despite
      publication of various guidelines and standards, and numerous initiatives aimed
      at improving nutritional care, there is still much to do if older people who are
      malnourished or at risk of malnutrition are to receive the help and support they
      need. This article outlines a free online tool launched by the British
      Association for Parenteral and Enteral Nutrition that helps staff in NHS and
      social care settings measure the quality of the nutritional care they provide. It
      explains how use of the tool by nurses caring for older people can benefit
      patients. Nurses should take the lead in multidisciplinary teams to measure
      nutritional care provided to older patients. This will enable identification of
      good practice and areas for improvement. 

PMID- 27029989
TI  - Transcultural nursing strategies for carers of people with dementia.
AB  - Caring for a family member with dementia is stressful, and carers from all
      backgrounds often feel overwhelmed and under-supported. Professional and family
      carers' perceptions of the challenges and satisfactions of caring are influenced
      by culturally derived expectations. However, experiences of caring often differ
      from stereotypical norms. Experiences of carer stress and beliefs about the
      nature and extent of support that can be expected from social networks and
      statutory services may differ between cultural groups in the UK, but sensitive
      advice, information, and emotional and practical support are universally
      required. Transcultural comparisons reveal similarities between carers' needs and
      enable identification of values-based culturally congruent recommendations that
      nurses can use to promote black and Asian minority ethnic carers' confidence and
      wellbeing. This article, based on practice experience and a literature review,
      explores the effect of caring among different cultural groups and offers
      recommendations for culturally congruent interventions to support carers. It
      provides evidence-based guidance to enable nurses to meet their responsibilities
      for transcultural working, as laid out in the Care Act 2014. A scenario
      illustrates recommendations for practice. 

PMID- 27029990
TI  - Applying comprehensive geriatric assessment to investigate falls.
AB  - This is the second article in a short series that presents case study examples of
      the use of comprehensive geriatric assessment (CGA) in different clinical
      settings. CGA is a holistic assessment model designed to determine frail older
      people's medical and mental health status, as well as functional, social and
      environmental issues. When applied by nurses, it can enable individualised
      planning for health, safety and wellbeing. This article presents the case of an
      older man who had a three-month history of falls. After his most recent fall he
      was admitted to an emergency department, where examination identified no
      significant abnormal pathology, and subsequently to a nurse-led older person's
      clinic. The article describes how a CGA approach was adopted to assess the man,
      establish an underlying diagnosis of Parkinson's disease, and develop a
      personalised care plan to address immediate falls risk and long-term planning. 

PMID- 27029991
TI  - Interaction between community pharmacists and community nurses in dementia care.
AB  - There has been little research that explores the interaction between community
      pharmacists and community nurses and how this interaction could benefit people
      affected by dementia. Using information taken from a larger study, this article
      presents the views of community pharmacists and one community nurse on how their
      communication, information sharing and team integration may improve care for this
      patient group. The community pharmacists reported positive attitudes to
      supporting people affected by dementia, but they highlighted barriers to
      integrated team working. In contrast, the community nurse conveyed the belief
      that the community pharmacist was an integrated member of the community health
      team. Community pharmacists and community nurses are keen to interact with each
      other to support people affected by dementia, but this interaction stops short of
      collaborative, integrated team working. Further research is needed to address
      this issue. 

PMID- 27029992
TI  - Passion for nursing.

PMID- 27029993
TI  - Biomechanical evaluation of CIBOR spine interbody fusion device.
AB  - BACKGROUND: The CIBOR PEEK spinal interbody fusion device is an anterior lumbar
      interbody fusion construct with a hollow center designed to accommodate an
      osteoinductive carbon foam insert to promote bony ingrowth to induce fusion where
      rigid stabilization is needed. METHODS: Three different sizes of the device were
      investigated. Part-I: implants were tested under axial compression and rotation
      using polyurethane foam blocks. Part-II: simulated 2-legged stance using
      cadaveric specimen using the L5-S1 lumbar spine segment. Part-III: a survey
      feedback form was used to investigate two orthopedic surgeons concern regarding
      the implant. RESULTS: In Part-I, the subsidence hysteresis under axial
      compression loading was found to be statistical significant difference between
      these three implant sizes. It was noted that the implants had migration as
      rotation applied, and the amount of subsidence was a factor of the axial
      compression loads applied. In Part-II, a minor subsidence and carbon foam debris
      were observed when compared to each implant size. Poor contact surface of the
      implant with the end plates of the L5 or S1 vertebrae from the anterior view
      under maximum loads was observed; however, the implant seemed to be stable. Each
      surgeon has their own subjective opinion about the CIBOR implant. DISCUSSION: Two
      out of the three different sizes of the device (medium and large sizes) provided
      appropriate rigid stabilization at the physiological loads. Neither orthopedic
      surgeon was 100% satisfied with overall performance of the implant, but felt
      potential improvement could be made. CLINICAL RELEVANCE: This study indicates an
      option for operative treatment of spine interbody fusion, as the CIBOR spine
      interbody fusion device has a hollow center. This hollow center is designed to
      accommodate a carbon foam insert to promote bony ingrowth. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1157-1168,
      2017.

PMID- 27029994
TI  - The influence of polymer purification on the efficiency of poly(3
      hexylthiophene):fullerene organic solar cells.
AB  - We report the influence of different polymer purification procedures on the
      photovoltaic performance of bulk heterojunction solar cells formed from binary
      blends of poly(3-hexylthiophene) (P3HT) and fullerenes. Selective Soxhlet
      extractions and metal scavenging agents were used to remove residual monomer,
      magnesium salt by-products and catalyst from high-weight P3HT (Mw 121 kg/mol, PDI
      1.8, RR 99%) synthesised by the Grignard metathesis (GRIM) polymerization route.
      Using phenyl-C61-butyric acid methyl ester (PC60BM) as an electron acceptor, we
      observed an increase in average power conversion efficiency from 2.3 to 4.8% in
      going from crude to fully purified material. Using indene-C60 bisadduct (IC60BA)
      in place of PC60BM, we observed a further increase to an average value of 6.6% -
      high for a bulk heterojunction formed from a binary blend of P3HT and C60
      fullerene derivatives. 

PMID- 27029995
TI  - Low dose of protein A pretreatment can alleviate the inflammatory reaction and
      the bio-safety was evaluated in vivo.
AB  - BACKGROUND: Staphylococcal protein A (SPA) is a protein of Staphylococcus aureus.
      Up to now, there have been many studies on the biological activities of SPA. Some
      reported effects of SPA pretreatment on septic shock in mouse models but there is
      no study which reports the role of SPA pretreatment on the infected incision.
      METHODS: According to count results, bacterial suspension was set at a density of
      ~1.8 * 10(9) colony forming units/mL. BALB/c mice were anesthetized via
      intraperitoneal injection with pentobarbital sodium. A longitudinal skin incision
      was made on the medial side of the right thigh. The length of the incision was 5
      mm, and the depth was ~3 mm. The bacterial suspension was gradually dripped and
      embrocated onto the incision surface to make the wound infection model. Before
      making the wound infection model for 48 hours and 24 hours, mice were retreated
      with SPA via intraperitoneal injection. Rats were intraperitoneally injected with
      SPA 1 mg/kg and the control group was injected with sterile saline to evaluate
      the biological safety of the best pretreatment dose. RESULTS: A 1-mL bacterial
      suspension can be utilized to make the wound infection model of BALB/c mouse
      lower limb. SPA pretreatment can reduce the inflammatory reactions in wound
      methicillin-resistant Staphylococcus aureus infection mouse model and the best
      pretreatment dose is 1 mg/kg. Intraperitoneal injection 1 mg/kg SPA does not
      destroy the functions of the organs. A 1-mg/kg SPA pretreatment can also reduce
      the inflammatory reactions in wound various bacterial infection mouse models.
      CONCLUSION: SPA pretreatment can effectively decrease the infected severity of a
      wound infected by various bacteria in a BALB/c mouse model. The best pretreatment
      dose is 1 mg/kg, and this dose does not damage organ function in rats up to a
      point.

PMID- 27029996
TI  - Laboratory observations of slow earthquakes and the spectrum of tectonic fault
      slip modes.
AB  - Slow earthquakes represent an important conundrum in earthquake physics. While
      regular earthquakes are catastrophic events with rupture velocities governed by
      elastic wave speed, the processes that underlie slow fault slip phenomena,
      including recent discoveries of tremor, slow-slip and low-frequency earthquakes,
      are less understood. Theoretical models and sparse laboratory observations have
      provided insights, but the physics of slow fault rupture remain enigmatic. Here
      we report on laboratory observations that illuminate the mechanics of slow-slip
      phenomena. We show that a spectrum of slow-slip behaviours arises near the
      threshold between stable and unstable failure, and is governed by frictional
      dynamics via the interplay of fault frictional properties, effective normal
      stress and the elastic stiffness of the surrounding material. This generalizable
      frictional mechanism may act in concert with other hypothesized processes that
      damp dynamic ruptures, and is consistent with the broad range of geologic
      environments where slow earthquakes are observed. 

PMID- 27029997
TI  - Electrospun nanofibres in agriculture and the food industry: a review.
AB  - The interesting characteristics of electrospun nanofibres, such as high surface
      to-volume ratio, nanoporosity, and high safety, make them suitable candidates for
      use in a variety of applications. In the recent decade, electrospun nanofibres
      have been applied to different potential fields such as filtration, wound
      dressing, drug delivery, etc. and a significant number of review papers have been
      published in these fields. However, the use of electrospun nanofibres in
      agriculture is comparatively novel and is still in its infancy. In this paper,
      the specific applications of electrospun nanofibres in agriculture and food
      science, including plant protection using pheromone-loaded nanofibres, plant
      protection using encapsulation of biocontrol agents, preparation of protective
      clothes for farm workers, encapsulation of agrochemical materials,
      deoxyribonucleic acid extraction in agricultural research studies, pre
      concentration and measurement of pesticides in crops and environmental samples,
      preparation of nanobiosensors for pesticide detection, encapsulation of food
      materials, fabrication of food packaging materials, and filtration of beverage
      products are reviewed and discussed. This paper may help researchers develop the
      use of electrospun nanofibres in agriculture and food science to address some
      serious problems such as the intensive use of pesticides. (c) 2016 Society of
      Chemical Industry.

PMID- 27029998
TI  - Formation of Heterocyclic Aromatic Amines and Migration Level of Bisphenol-A in
      Sous-Vide-Cooked Trout Fillets at Different Cooking Temperatures and Cooking
      Levels.
AB  - The effects of different cooking temperatures (65, 75, and 85  degrees C) and
      cooking levels (medium and well) on some quality properties, the formation of
      heterocyclic aromatic amines (HCAs), and the migration level of bisphenol-A (BPA)
      in trout fillets cooked by sous-vide were investigated. As a result, as expected,
      cooking caused a reduction in water content of the samples, whereas pH, TBARS,
      L*, and b* values increased. Cooking loss values ranged between 14.78 and 20.51%.
      Whereas IQ, MeIQ, 7,8-DiMeIQx, 4,8-DiMeIQx, PhIP, AalphaC and MeAalphaC could not
      be detected in the analyzed samples, varying levels of IQx (up to 0.16 ng/g) and
      MeIQx (up to 5.66 ng/g) were detected. It was determined that total HCA amounts
      ranged between 1.28 and 5.75 ng/g, and all or a big part of the total HCAs
      belonged to MeIQx. In addition, the migration level of BPA in sous-vide-cooked
      samples ranged between 4.93 and 27.11 ng/g. 

PMID- 27029999
TI  - Opinions and Beliefs About Telemedicine for Emergency Treatment During Ambulance
      Transportation and for Chronic Care at Home.
AB  - BACKGROUND: Telemedicine is a valid alternative to face-to-face patient care in
      many areas. However, the opinion of all stakeholders is decisive for successful
      adoption of this technique, especially as telemedicine expands into novel domains
      such as emergency teleconsultations during ambulance transportation and chronic
      care at home. OBJECTIVE: We evaluate the viewpoints of the broad public,
      patients, and professional caregivers in these situations. METHODS: A 10-question
      survey was developed and obtained via face-to-face interviews of visitors at the
      Universitair Ziekenhuis Brussel (UZB). The online questionnaire was also
      distributed among professional caregivers via the intranet of the UZB and among
      the broad public using social media. RESULTS: In total, 607 individuals responded
      to the questionnaire, expressing a positive opinion regarding telemedicine for in
      ambulance emergency treatment and for chronic care at home. Privacy issues were
      not perceived as relevant, and most respondents were ready to participate in
      future teleconsultations. Lack of telecommunication knowledge (213/566, 37.6%)
      was the only independent factor associated with rejection of telemedicine at home
      and respondents via social media (250/607, 41.2%) were less concerned about
      privacy issues than respondents via face-to-face interviews (visitors, 234/607,
      38.6%). The visitors were more positive towards in-ambulance telemedicine and
      more likely to agree with future participation in teleconsultations than
      respondents via social media. CONCLUSIONS: The broad public, professional
      caregivers, and patients reported a positive attitude towards telemedicine for
      emergency treatment during ambulance transportation and for chronic care at home.
      These results support further improvement of telemedicine solutions in these
      domains.

PMID- 27030000
TI  - Distribution of human single-nucleotide polymorphisms is approximated by the
      power law and represents a fractal structure.
AB  - Single-nucleotide polymorphisms (SNPs) are one of the main causes of evolution.
      The distribution of human SNPs, which were examined in detail genomewide, was
      analyzed. Three discrete databases of human SNPs were used for this analysis, and
      similar results were obtained from these databases. It was found that the
      distribution of the distance between SNPs was approximated by the power law, and
      the shape of the regions including SNPs had the so-called fractal structure.
      Although the reason why the distribution of SNPs obeys such a certain law of
      physics is unclear, a speculation was attempted in connection with the three
      dimensional structure of human chromatin which has a fractal structure. 

PMID- 27030001
TI  - A Simple Algorithm for Population Classification.
AB  - A single-nucleotide polymorphism (SNP) is a variation in the DNA sequence that
      occurs when a single nucleotide in the genome differs across members of the same
      species. Variations in the DNA sequences of humans are associated with human
      diseases. This makes SNPs as a key to open up the door of personalized medicine.
      SNP(s) can also be used for human identification and forensic applications.
      Compared to short tandem repeat (STR) loci, SNPs have much lower statistical
      testing power for individual recognition due to the fact that there are only 3
      possible genotypes for each SNP marker, but it may provide sufficient information
      to identify the population to which a certain samples may belong. In this report,
      using eight SNP markers for 641 samples, we performed a standard statistical
      classification procedure and found that 86% of the samples could be classified
      accurately under a two-population model. This study suggests the potential use of
      SNP(s) in population classification with a small number (n <= 8) of genetic
      markers for forensic screening, biodiversity and disaster victim controlling. 

PMID- 27030002
TI  - Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction.
AB  - Left ventricular noncompaction cardiomyopathy (LVNC) is a clinically
      heterogeneous disorder characterized by a trabecular meshwork and deep
      intertrabecular myocardial recesses that communicate with the left ventricular
      cavity. Several genetic causes of LVNC have been reported, with variable modes of
      inheritance, including autosomal dominant and X-linked inheritance, but
      relatively few responsible genes have been identified. A NGS workflow, based on a
      panel of 95 genes developed for sequencing most prevalent sudden cardiac death
      causing genes, was used to make a rapid and costless molecular diagnosis in two
      siblings with a severe noncompaction cardiomyopathy starting prenatally and
      leading to rapid cardiac failure. For the first time, a total homozygous PKP2
      deletion was identified. This molecular defect was further confirmed by MLPA and
      array-comparative genomic hybridization (CGH). Heterozygous PKP2 mutations are
      usually reported in a significant proportion of Arrhythmogenic Right Ventricular
      Cardiomyopathy cases. Our results show, for the first time, the involvement of
      PKP2 in severe cardiomyopathy with ventricular non compaction.

PMID- 27030003
TI  - Use of Space and Human Rights: Planning Dementia Friendly Settings.
AB  - Environmental psychology has been a topic of great interest for many researchers
      in the field of aging and dementia. Thus, several orientations can be identified
      in the contemporary scientific literature concerning environmental design for
      people with dementia. In this article, we discuss recent research on
      environmental design models for people with dementia and propose an approach
      referring to the concept of use of space and human rights.We use a methodology
      based on observation of special care units to determine an environmental design
      framework that should be taken into account when designing residential facilities
      for people with dementia. Content analysis identified 6 primary dimensions and 13
      secondary dimensions relevant to the rights of people with dementia. We then
      discuss the results according to the related literature in environmental
      psychology and gerontology in terms of well-being and quality of life.

PMID- 27030004
TI  - Cutaneuos findings in patients with predialysis chronic kidney disease.
AB  - BACKGROUND: Several cutaneous findings are seen in dialysis dependent chronic
      kidney disease (CKD) patients. However, there are only a few small studies on
      cutaneous findings in predialysis CKD patients. We aimed to determine cutaneous
      findings in predialysis CKD patients. METHODS: This was a cross-sectional study.
      Consecutive predialysis CKD patients from nephrology outpatient clinic in a
      university affiliated hospital were recruited to this study. Detailed
      dermatologic examination was performed by a senior dermatologist. Blood urea,
      creatinine, hepatitis B surface antigen and hepatitis C antibody test were
      studied for each participant. RESULTS: A total of 365 consecutive predialysis CKD
      patients (stages 2-5) included in the study. Three hundred and fifty-eight
      patients (98.1%) had at least one dermatologic finding. The most common cutaneous
      finding was xerosis (64.9%) followed by hair findings (41.4%), pruritus (19.2%),
      pigmentary changes (17.5%), nail findings (15.3%) and oral mucosal findings
      (9.3%). Longitudinal striations was the most common nail finding, diffuse brown
      hyperpigmentation was the most common pigmentary change, coated tongue was the
      most common oral mucosal finding and androgenetic alopecia was the most common
      hair finding. Frequency and diversity of dermatologic findings did not change
      across CKD stages. CONCLUSIONS: This is the largest study investigating
      dermatologic findings in a well-characterized predialysis CKD patient population.
      We found that at least one cutaneous finding was present in almost all of the CKD
      patients. Cutaneous findings are very common and diverse among predialysis CKD
      patients.

PMID- 27030005
TI  - [Heart rate and outcome in patients with acute and chronic heart failure].
AB  - Heart rate (HR) is not only a physical sign but also a biomarker. High HR in
      several cardiac disorders is associated with increased mortality. In heart
      failure (HF), HR represents an important therapeutic target, both in the acute
      and chronic phase. Beta-blockers are a milestone of recommended treatments in HF
      patients with reduced ejection fraction. However, hemodynamic profile or
      intolerance may limit the use or the optimization of beta-blocker treatment, both
      during hospitalization and outpatient follow-up. More recently, ivabradine has
      become available, a drug that lowers HR by blocking the I(f) current in the
      pacemaker cells at the sinoatrial node level. In the SHIFT trial, ivabradine was
      shown to improve the outcome of patients with chronic HF, in sinus rhythm, with
      HR >70 b/min while on beta-blockers. Preliminary data have shown that this drug
      has a good safety profile and lowers effectively HR even during hospitalization
      due to worsening HF. However, further studies are warranted to understand if an
      earlier administration of ivabradine can lead to a better prognosis beyond
      symptom control and improved hemodynamics. In patients with atrial fibrillation
      and HF, the target is the restoration of sinus rhythm, alternatively rate control
      should be pursued with beta-blockers, amiodarone or digitalis, even if there is
      no clear evidence of an association between ventricular rate response in patients
      with atrial fibrillation at discharge after an HF hospitalization and major
      cardiovascular events. In this review, the studies that point to a role of HR
      both as a biomarker and a therapeutic target in patients with acute and chronic
      HF are described. In addition, the proportions of patients who do not reach
      target HR values at discharge after an acute decompensated HF episode or in the
      chronic phase are evaluated based on the Italian registries.

PMID- 27030006
TI  - Crystal structure, photoluminescence and electroluminescence of three bluish
      green light-emitting iridium complexes.
AB  - Three bis-cyclometalated iridium complexes ((TPP)2Ir(acac), (TPP)2Ir(tpip) and
      (TPP)2Ir(pic)) with 2-(2-trifluoromethyl)pyrimidine-pyridine (TPP) as the main
      ligand, 2,4-pentanedionate (acac), tetraphenylimidodiphosphinate (tpip) and
      picolinate (pic) as the ancillary ligands, respectively, were prepared. Their
      photoluminescence and electrochemistry properties were investigated in detail,
      and (TPP)2Ir(tpip) was also examined by X-ray crystallography. These complexes
      show bluish green emission with a quantum efficiency of 11-14%. The organic light
      emitting diodes (OLEDs) with the structure of ITO/TAPC (1,1-bis[4-(di-p
      tolylamino)phenyl]cyclohexane, 40 nm)/mCP (1,3-bis(9H-carbazol-9-yl)benzene, 10
      nm)/Ir complex (8 wt%):PPO21 (3-(diphenylphosphoryl)-9-(4
      (diphenylphosphoryl)phenyl)-9H-carbazole, 25 nm)/TmPyPB (1,3,5-tri(m-pyrid-3-yl
      phenyl)benzene, 50 nm)/LiF (1 nm)/Al (100 nm) were fabricated to evaluate the
      potential application of these complexes. A (TPP)2Ir(tpip) emitter based device
      showed the best performance of a maximum current efficiency (etac) value of 37.61
      cd A(-1) and a maximum external quantum efficiency (EQE) of 13.7% with low
      efficiency roll-off.

PMID- 27030007
TI  - S-Nitrosothiols as Platforms for Topical Nitric Oxide Delivery.
AB  - Nitric oxide (NO) is a small radical species involved in several fundamental
      physiological processes, including the control of vascular tone, the immune
      response and neuronal signalling. Endothelial dysfunction with the decreased NO
      bioavailability is the underlying cause of several diseases and has led to the
      development of a wide range of systemic NO donor compounds to lower the blood
      pressure and control hypertensive crises. However, several potential therapeutic
      actions of NO, not related to the cardiovascular system, demand exclusively local
      actions. Primary S-nitrosothiols (RSNOs) are endogenously found NO carriers and
      donors and have emerged as platforms for the localized delivery of NO in topical
      applications. Formulations for this purpose have evolved from low molecular
      weight RSNOs incorporated in polymeric films, hydrogels and viscous vehicles, to
      polymeric RSNOs where the SNO moiety is covalently bound to the polymer backbone.
      The biological actions displayed by these formulations include the increase in
      dermal vasodilation, the acceleration of wound healing, the killing of infectious
      microorganisms and an analgesic action against inflammatory pain. This MiniReview
      focuses on the state of the art of experimental topical formulations for NO
      delivery based on S-nitrosothiols and their potential therapeutic applications.

PMID- 27030008
TI  - Cumulative Advantage, Cumulative Disadvantage, and Evolving Patterns of Late-Life
      Inequality.
AB  - Purpose of the Study: Earlier studies have identified a pattern of cumulative
      advantage leading to increased within-cohort economic inequality over the life
      course, but there is a need to better understand how levels of inequality by age
      have changed in the evolving economic environment of recent decades. We utilized
      Survey of Income and Program Participation (SIPP) data to compare economic
      inequality across age groups for 2010 versus 1983-1984. Design and Methods: We
      examined changing age profiles of inequality using a summary measure of economic
      resources taking into account income, annuitized value of wealth, and household
      size. We adjusted for survey underreporting of some income and asset types, based
      on National Income Accounts and other independent estimates of national
      aggregates. We examined inequality by age with Gini coefficients. Results: Late
      life (65+) inequality increased between the 2 periods, with Gini coefficients
      remaining higher than during the working years, but with a less steep age
      difference in inequality in 2010 than in 1983-1984. Inequality increased sharply
      within each cohort, particularly steeply in Depression-era, war-baby, and leading
      edge baby boom cohorts. The top quintile of elderly received increasing shares of
      most income sources. Implications: Increasing inequality among older people, and
      especially in cohorts approaching late life, presages upcoming financial
      challenges for elderly persons in the lower part of the income distribution.
      Implications of this increasingly high-inequality late-life environment need to
      be carefully evaluated as changes are considered in Social Security and other
      safety-net institutions, which moderate impacts of economic forces that drive
      increasingly disparate late-life economic outcomes.

PMID- 27030009
TI  - Functional and Structural Characterization of Bub3.BubR1 Interactions Required
      for Spindle Assembly Checkpoint Signaling in Human Cells.
AB  - The spindle assembly checkpoint (SAC) is an essential safeguarding mechanism
      devised to ensure equal chromosome distribution in daughter cells upon mitosis.
      The proteins Bub3 and BubR1 are key components of the mitotic checkpoint complex,
      an essential part of the molecular machinery on which the SAC relies. In the
      present work we have performed a detailed functional and biochemical
      characterization of the interaction between human Bub3 and BubR1 in cells and in
      vitro Our results demonstrate that genetic knockdown of Bub3 abrogates the SAC,
      promotes apoptosis, and inhibits the proliferation of human cancer cells. We also
      show that the integrity of the human mitotic checkpoint complex depends on the
      specific recognition between BubR1 and Bub3, for which the BubR1 Gle2 binding
      sequence motif is essential. This 1:1 binding event is high affinity, enthalpy
      driven and with slow dissociation kinetics. The affinity, kinetics, and
      thermodynamic parameters of the interaction are differentially modulated by small
      regions in the N and C termini of the Gle2 binding domain sequence, suggesting
      the existence of "hotspots" for this protein-protein interaction. Furthermore, we
      show that specific disruption of endogenous BubR1.Bub3 complexes in human cancer
      cells phenocopies the effects observed in gene targeting experiments. Our work
      enhances the current understanding of key members of the SAC and paves the road
      for the pursuit of novel targeted cancer therapies based on SAC inhibition.

PMID- 27030010
TI  - Protein Kinase D and Gbetagamma Subunits Mediate Agonist-evoked Translocation of
      Protease-activated Receptor-2 from the Golgi Apparatus to the Plasma Membrane.
AB  - Agonist-evoked endocytosis of G protein-coupled receptors has been extensively
      studied. The mechanisms by which agonists stimulate mobilization and plasma
      membrane translocation of G protein-coupled receptors from intracellular stores
      are unexplored. Protease-activated receptor-2 (PAR2) traffics to lysosomes, and
      sustained protease signaling requires mobilization and plasma membrane
      trafficking of PAR2 from Golgi stores. We evaluated the contribution of protein
      kinase D (PKD) and Gbetagamma to this process. In HEK293 and KNRK cells, the PAR2
      agonists trypsin and 2-furoyl-LIGRLO-NH2 activated PKD in the Golgi apparatus,
      where PKD regulates protein trafficking. PAR2 activation induced translocation of
      Gbetagamma, a PKD activator, to the Golgi apparatus, determined by
      bioluminescence resonance energy transfer between Ggamma-Venus and giantin-Rluc8.
      Inhibitors of PKD (CRT0066101) and Gbetagamma (gallein) prevented PAR2-stimulated
      activation of PKD. CRT0066101, PKD1 siRNA, and gallein all inhibited recovery of
      PAR2-evoked Ca(2+) signaling. PAR2 with a photoconvertible Kaede tag was
      expressed in KNRK cells to examine receptor translocation from the Golgi
      apparatus to the plasma membrane. Irradiation of the Golgi region (405 nm)
      induced green-red photo-conversion of PAR2-Kaede. Trypsin depleted PAR2-Kaede
      from the Golgi apparatus and repleted PAR2-Kaede at the plasma membrane.
      CRT0066101 inhibited PAR2-Kaede translocation to the plasma membrane. CRT0066101
      also inhibited sustained protease signaling to colonocytes and nociceptive
      neurons that naturally express PAR2 and mediate protease-evoked inflammation and
      nociception. Our results reveal a major role for PKD and Gbetagamma in agonist
      evoked mobilization of intracellular PAR2 stores that is required for sustained
      signaling by extracellular proteases. 

PMID- 27030012
TI  - Ebola is no longer a public health emergency, says WHO.

PMID- 27030011
TI  - Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein
      Aggregation in a Threshold-dependent Manner.
AB  - The microtubule-associated protein tau has a critical role in Alzheimer disease
      and related tauopathies. There is accumulating evidence that tau aggregates
      spread and replicate in a prion-like manner, with the uptake of pathological tau
      seeds causing misfolding and aggregation of monomeric tau in recipient cells.
      Here we focused on small extracellular vesicles enriched for exosomes that were
      isolated from the brains of tau transgenic rTg4510 and control mice. We found
      that these extracellular vesicles contained tau, although the levels were
      significantly higher in transgenic mice that have a pronounced tau pathology. Tau
      in the vesicles was differentially phosphorylated, although to a lower degree
      than in the brain cells from which they were derived. Several phospho-epitopes
      (AT8, AT100, and AT180) thought to be critical for tau pathology were undetected
      in extracellular vesicles. Despite this, when assayed with FRET tau biosensor
      cells, extracellular vesicles derived from transgenic mice were capable of
      seeding tau aggregation in a threshold-dependent manner. We also observed that
      the dye used to label extracellular vesicle membranes was still present during
      nucleation and formation of tau inclusions, suggesting either a role for
      membranes in the seeding or in the process of degradation. Together, we clearly
      demonstrate that extracellular vesicles can transmit tau pathology. This
      indicates a role for extracellular vesicles in the transmission and spreading of
      tau pathology. The characteristics of tau in extracellular vesicles and the
      seeding threshold we identified may explain why tau pathology develops very
      slowly in neurodegenerative diseases such as Alzheimer disease.

PMID- 27030014
TI  - Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles.
AB  - Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials
      for liver diseases and solid tumors, but remain a challenge for manipulating
      leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest
      pathogens and defend the body through a complex network. They are also involved
      in the pathogeneses of inflammation, viral infection, autoimmunity and cancers.
      Modulating gene expression in leukocytes using siRNAs holds great promise to
      treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce
      with siRNAs and are spread throughout the body often located deep in tissues,
      therefore developing an efficient systemic delivery strategy is still a
      challenge. Here, we discuss recent advances in siRNA delivery to leukocyte
      subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus
      mainly on lipid-based nanoparticles (LNPs) comprised of new generation of
      ionizable lipids and their ability to deliver siRNA to primary or malignant
      leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to
      subsets of leukocytes and we detail a novel microfluidic mixing technology that
      could aid in changing the landscape of process development of LNPs from a lab
      tool to a potential novel therapeutic modality.

PMID- 27030013
TI  - Neuropathological basis of nonmotor manifestations of Parkinson's disease.
AB  - Nonmotor manifestations of Parkinson's disease (PD) can begin well before motor
      PD begins. It is now clear, from clinical and autopsy studies, that there is
      significant Lewy-type alpha-synucleinopathy present outside the nigro-striatal
      pathway and that this may underlie these nonmotor manifestations. This review
      discusses neuropathological findings that may underlie nonmotor symptoms that
      either predate motor findings or occur as the disease progresses. (c) 2016
      International Parkinson and Movement Disorder Society.

PMID- 27030016
TI  - Physiological and iTRAQ-Based Proteomic Analyses Reveal the Function of
      Spermidine on Improving Drought Tolerance in White Clover.
AB  - Endogenous spermidine interacting with phytohormones may be involved in the
      regulation of differentially expressed proteins (DEPs) associated with drought
      tolerance in white clover. Plants treated with or without spermidine (50 MUM)
      were subjected to 20% PEG 6000 nutrient solution to induce drought stress (50%
      leaf-relative water content). The results showed that increased endogenous
      spermidine induced by exogenous spermidine altered endogenous phytohormones in
      association with improved drought tolerance, as demonstrated by the delay in
      water-deficit development, improved photosynthesis and water use efficiency, and
      lower oxidative damage. As compared to untreated plants, Spd-treated plants
      maintained a higher abundance of DEPs under drought stress involved in (1)
      protein biosynthesis (ribosomal and chaperone proteins); (2) amino acids
      synthesis; (3) the carbon and energy metabolism; (4) antioxidant and stress
      defense (ascorbate peroxidase, glutathione peroxidase, and dehydrins); and (5) GA
      and ABA signaling pathways (gibberellin receptor GID1, ABA-responsive protein 17,
      and ABA stress ripening protein). Thus, the findings of proteome could explain
      the Spd-induced physiological effects associated with drought tolerance. The
      analysis of functional protein-protein networks further proved that the
      alteration of endogenous spermidine and phytohormones induced the interaction
      among ribosome, photosynthesis, carbon metabolism, and amino acid biosynthesis.
      These differences could contribute to improved drought tolerance.

PMID- 27030017
TI  - Physical Fighting Among Male and Female Adolescents of Military Families: Results
      From a Representative Sample of High School Students.
AB  - The impact of family military involvement on adolescent mental health and
      substance abuse is well established, but little is known about other behavioral
      health outcomes such as physical fighting. We assessed the relationship between
      family military involvement and physical fighting in a representative sample of
      3,928 high school students. Weighted logistic regression was used to determine
      whether adolescents from military families had higher odds of fighting and
      fighting on school property compared with adolescents of non-military families
      after controlling for demographics, substance use, depressive symptoms, and
      bullying victimization. We also assessed the cumulative impact of multiple risk
      factors on fighting outcomes. Overall, 23.5% of high school students reported
      physical fighting and 7.0% reported physical fighting at school. Youth from
      military families had higher odds of physical fighting (adjusted odds ratios
      [AOR] = 1.69; 95% confidence interval [CI] = [1.27, 2.25]) and physical fighting
      on school property (AOR = 1.98; 95% CI = [1.16, 3.39]). In models stratified by
      gender, family military involvement remained independently associated with
      physical fighting and physical fighting at school for males (AOR = 1.74; 95% CI =
      [1.15, 2.65] and AOR = 2.21; 95% CI = [1.03, 4.74]) and females (AOR = 1.65; 95%
      CI = [1.11, 2.45] and AOR = 1.88; 95% CI = [1.01, 3.50]). The odds of engaging in
      each physical fighting outcome increased as the cumulative number of risk factors
      increased. School-based interventions aimed at addressing fighting should be
      tailored to fit the unique needs of adolescents in military families,
      particularly those with additional risk factors.

PMID- 27030015
TI  - pH Induced Conformational Transitions in the Transforming Growth Factor beta
      Induced Protein (TGFbetaIp) Associated Corneal Dystrophy Mutants.
AB  - Most stromal corneal dystrophies are associated with aggregation and deposition
      of the mutated transforming growth factor-beta induced protein (TGFbetaIp). The
      4(th)_FAS1 domain of TGFbetaIp harbors ~80% of the mutations that forms
      amyloidogenic and non-amyloidogenic aggregates. To understand the mechanism of
      aggregation and the differences between the amyloidogenic and non-amyloidogenic
      phenotypes, we expressed the 4(th)_FAS1 domains of TGFbetaIp carrying the
      mutations R555W (non-amyloidogenic) and H572R (amyloidogenic) along with the wild
      type (WT). R555W was more susceptible to acidic pH compared to H572R and
      displayed varying chemical stabilities with decreasing pH. Thermal denaturation
      studies at acidic pH showed that while WT did not undergo any conformational
      transition, the mutants exhibited a clear pH-dependent irreversible conversion
      from alphabeta conformation to beta-sheet oligomers. The beta-oligomers of both
      mutants were stable at physiological temperature and pH. Electron microscopy and
      dynamic light scattering studies showed that beta-oligomers of H572R were larger
      compared to R555W. The beta-oligomers of both mutants were cytotoxic to primary
      human corneal stromal fibroblast (pHCSF) cells. The beta-oligomers of both
      mutants exhibit variations in their morphologies, sizes, thermal and chemical
      stabilities, aggregation patterns and cytotoxicities. 

PMID- 27030018
TI  - Medical Narrative and the Rhetoric of Identification: The Many Faces of Anna
      White Dildane.
AB  - When Anna White Dildane, a prostitute and heroin addict, was committed to the
      Laboratory of Social Hygiene (LSH) in 1917, she was treated by a staff that
      anticipated the methods of the biopsychosocial model later developed by Engel.
      That is to say, the staff members believed that Anna's rehabilitation was
      contingent on a scientific diagnosis of the physical, mental, and social factors
      that underlay her condition. However, using Anna and the LSH as a case study, we
      draw from Latour to show the limitations of this "modern" method of diagnosis and
      treatment that persists today. Using Burke, we advocate for a pragmatic
      orientation focused on creating rhetorically oriented narratives whose aim is to
      help patients make judgments about their health and future, namely, by bringing
      about the experience of "form" capable of constituting new types of
      identification. Effective medical rhetoric thus adopts a method of persuasion
      that begins with the narrative and self-understanding of the patient, links
      aspects of that narrative with the technical expertise of physicians and other
      health care providers, and crafts a new, more specialized narrative attentive to
      the desires and constraints of a patient's form of identification that is
      ultimately the seat of judgment.

PMID- 27030020
TI  - Characterization of Fe2+ ions in Fe,H/SSZ-13 zeolites: FTIR spectroscopy of CO
      and NO probe molecules.
AB  - The IR spectra of adsorbed CO and NO probe molecules were used to characterize
      the coordination chemistry of Fe(2+) ions in solution ion exchanged Fe,H/SSZ-13
      zeolites. The effects of Fe ion exchange levels, as well as the sample pre
      treatment conditions, on the adsorption of these probe molecules were
      investigated. The ion exchange levels (in the range of the study) did not affect
      significantly the IR spectra of either probe molecule, and the IR features and
      their intensity ratios were very similar. Experiments with both probe molecules
      substantiated the presence of two distinct types of Fe(2+) ions in cationic
      positions. We assign these two Fe(2+) ions to two distinct cationic positions:
      Fe(2+) in 6R and 8R positions. NO initially adsorbs preferentially onto Fe(2+)
      sites in the 6R position, and then populates sites in the 8R. Fe(2+) ions in the
      8R positions require the interaction of more than one NO molecule to move them
      out from their adsorbate-free cationic positions. As soon as they move from their
      stable positions, they are able to bind to multiple NO molecules, and form mostly
      tri-nitrosyls. These tri-nitrosyls, however, are only stable in the presence of
      gas phase NO; under dynamic vacuum they lose one of the NO molecules from their
      coordination sphere and form stable di-nitrosyls. The adsorption of CO is much
      weaker on Fe(2+) sites than that of NO, and requires cryogenic sample
      temperatures to initiate CO adsorption. Under the conditions applied in this
      study, only mono-carbonyl formation was observed. Reduction in H2 at 773 K
      increased the number of Fe(2+) adsorption sites, primarily in the 8R locations.
      Oxidation by N2O, on the other hand, selectively reduced the adsorption of both
      CO and NO on the Fe(2+) sites in 8R positions. Adsorbed oxygen left behind from
      the decomposition of N2O at 573 K readily reacted with CO to produce CO2 even at
      150 K. 

PMID- 27030021
TI  - Editorial.

PMID- 27030022
TI  - Social Science in Society.

PMID- 27030023
TI  - Cross-species analysis of Fc engineered anti-Lewis-Y human IgG1 variants in human
      neonatal receptor transgenic mice reveal importance of S254 and Y436 in binding
      human neonatal Fc receptor.
AB  - IgG has a long half-life through engagement of its Fc region with the neonatal Fc
      receptor (FcRn). The FcRn binding site on IgG1 has been shown to contain I253 and
      H310 in the CH2 domain and H435 in the CH3 domain. Altering the half-life of IgG
      has been pursued with the aim to prolong or reduce the half-life of therapeutic
      IgGs. More recent studies have shown that IgGs bind differently to mouse and
      human FcRn. In this study we characterize a set of hu3S193 IgG1 variants with
      mutations in the FcRn binding site. A double mutation in the binding site is
      necessary to abrogate binding to murine FcRn, whereas a single mutation in the
      FcRn binding site is sufficient to no longer detect binding to human FcRn and
      create hu3S193 IgG1 variants with a half-life similar to previously studied
      hu3S193 F(ab')2 (t1/2beta, I253A, 12.23 h; H310A, 12.94; H435A, 12.57; F(ab')2,
      12.6 h). Alanine substitutions in S254 in the CH2 domain and Y436 in the CH3
      domain showed reduced binding in vitro to human FcRn and reduced elimination half
      lives in huFcRn transgenic mice (t1/2beta, S254A, 37.43 h; Y436A, 39.53 h; wild
      type, 83.15 h). These variants had minimal effect on half-life in BALB/c nu/nu
      mice (t1/2beta, S254A, 119.9 h; Y436A, 162.1 h; wild-type, 163.1 h). These
      results provide insight into the interaction of human Fc by human FcRn, and are
      important for antibody-based therapeutics with optimal pharmacokinetics for
      payload strategies used in the clinic.

PMID- 27030024
TI  - Functional brain networks associated with eating behaviors in obesity.
AB  - Obesity causes critical health problems including diabetes and hypertension that
      affect billions of people worldwide. Obesity and eating behaviors are believed to
      be closely linked but their relationship through brain networks has not been
      fully explored. We identified functional brain networks associated with obesity
      and examined how the networks were related to eating behaviors. Resting state
      functional magnetic resonance imaging (MRI) scans were obtained for 82
      participants. Data were from an equal number of people of healthy weight (HW) and
      non-healthy weight (non-HW). Connectivity matrices were computed with spatial
      maps derived using a group independent component analysis approach. Brain
      networks and associated connectivity parameters with significant group-wise
      differences were identified and correlated with scores on a three-factor eating
      questionnaire (TFEQ) describing restraint, disinhibition, and hunger eating
      behaviors. Frontoparietal and cerebellum networks showed group-wise differences
      between HW and non-HW groups. Frontoparietal network showed a high correlation
      with TFEQ disinhibition scores. Both frontoparietal and cerebellum networks
      showed a high correlation with body mass index (BMI) scores. Brain networks with
      significant group-wise differences between HW and non-HW groups were identified.
      Parts of the identified networks showed a high correlation with eating behavior
      scores. 

PMID- 27030025
TI  - Nonthermal Optical Emission Spectrometry: Direct Atomization and Excitation of
      Cadmium for Highly Sensitive Determination.
AB  - The low atomization and excitation capability of nonthermal microplasma, e.g.,
      dielectric barrier discharge (DBD), has greatly hampered its potential
      applications for the determination of metals in solution. In the present work, an
      inspiring development is reported for direct atomization and excitation of
      cadmium in aqueous solution by DBD and facilitates highly sensitive
      determination. A DBD microplasma is generated on the nozzle of a pneumatic
      micronebulizer to focus the DBD energy on a confined space and atomize/excite
      metals in the spray. Meanwhile, an appropriate sample matrix and nebulization in
      helium further improves the atomization and excitation capability of DBD. With
      cadmium as a model, its emission is recorded by a CCD spectrometer at 228.8 nm.
      By using an 80 MUL sample solution nebulized at 3 MUL s(-1), a linear range of 5
      1000 MUg L(-1) along with a detection limit of 1.5 MUg L(-1) is achieved, which
      is comparable to those obtained by commercial bulky inductively coupled plasma
      (ICP)-based instrumentations. 

PMID- 27030027
TI  - Identification of common, unique and polymorphic microsatellites among 73
      cyanobacterial genomes.
AB  - Microsatellites also known as Simple Sequence Repeats are short tandem repeats of
      1-6 nucleotides. These repeats are found in coding as well as non-coding regions
      of both prokaryotic and eukaryotic genomes and play a significant role in the
      study of gene regulation, genetic mapping, DNA fingerprinting and evolutionary
      studies. The availability of 73 complete genome sequences of cyanobacteria
      enabled us to mine and statistically analyze microsatellites in these genomes.
      The cyanobacterial microsatellites identified through bioinformatics analysis
      were stored in a user-friendly database named CyanoSat, which is an efficient
      data representation and query system designed using ASP.net. The information in
      CyanoSat comprises of perfect, imperfect and compound microsatellites found in
      coding, non-coding and coding-non-coding regions. Moreover, it contains PCR
      primers with 200 nucleotides long flanking region. The mined cyanobacterial
      microsatellites can be freely accessed at www.compubio.in/CyanoSat/home.aspx. In
      addition to this 82 polymorphic, 13,866 unique and 2390 common microsatellites
      were also detected. These microsatellites will be useful in strain identification
      and genetic diversity studies of cyanobacteria.

PMID- 27030028
TI  - Total femoral reconstruction with custom prosthesis for osteosarcoma.
AB  - BACKGROUND: The aim of this study was to assess total femur replacement for the
      treatment of femoral osteosarcomas. METHODS: Between January 1995 and January
      2012, 21 patients with a mean age of 21.8 years old were treated for femoral
      osteosarcomas with total femur replacement. All tumors were staged according to
      Enneking's criteria with one stage IIA case and 20 stage IIB cases. RESULTS: The
      survival of patients with osteosarcoma without metastases was 66.7% at 5 years.
      Twelve patients were alive with an overall mean follow-up of 71.2 months, and the
      mean postoperative functional score was 72.5% at their last follow-up.
      Superficial infection occurred in two patients, which were resolved by changing
      dressing and intravenous antibiotics. Deep infection occurred in one patient,
      which was an amputation by hip disarticulation. Patella fracture occurred in one
      patient, which was treated by open reduction and tension band fixation. Local
      recurrence was seen in one patient, which was an amputation by hip
      disarticulation. Pulmonary metastases were observed in nine patients and all the
      patients subsequently died of disease within 12 months. Aseptic loosening in
      tibial stem occurred in three patients, whose whole prosthesis was revised.
      CONCLUSIONS: Total femur replacement is a reliable method to restore mechanical
      and functional results after extensive resection of the femur.

PMID- 27030029
TI  - Infectious Enthusiasm! Larger than Life! That Laugh! That Smile! In Loving Memory
      of Richard G.H. (Dick) Cotton.

PMID- 27030030
TI  - A design thinking approach to evaluating interprofessional education.
AB  - The complex challenge of evaluating the impact of interprofessional education
      (IPE) on patient and community health outcomes is well documented. Recently, at
      the Radcliffe Institute for Advanced Study in the United States, leaders in
      health professions education met to help generate a direction for future IPE
      evaluation research. Participants followed the stages of design thinking, a
      process for human-centred problem solving, to reach consensus on recommendations.
      The group concluded that future studies should focus on measuring an intermediate
      step between learning activities and patient outcomes. Specifically, knowing how
      IPE-prepared students and preceptors influence the organisational culture of a
      clinical site as well as how the culture of clinical sites influences learners'
      attitudes about collaborative practice will demonstrate the value of educational
      interventions. With a mixed methods approach and an appreciation for context,
      researchers will be able to identify the factors that foster effective
      collaborative practice and, by extension, promote patient-centred care. 

PMID- 27030031
TI  - MORBID THOUGHTS AND SUICIDAL IDEATION IN IRAQ WAR VETERANS: THE ROLE OF DIRECT
      AND INDIRECT KILLING IN COMBAT.
AB  - BACKGROUND: Although research has identified numerous risk factors for military
      suicide, the contribution of combat exposure to suicide risk has not been clearly
      established. Previous studies finding no association of suicidality with combat
      exposure have employed overgeneral measures of exposure, which do not
      differentiate among the varieties of combat experiences. This study disaggregated
      the forms of combat exposure to assess the contribution of combat-related killing
      to morbid thoughts and suicidal ideation (MTSI) in National Guard troops deployed
      to Iraq. METHODS: We conducted parallel analyses of two related samples: a cross
      sectional sample (n = 1,665) having postdeployment interview data only and a
      longitudinal subsample (n = 922) having pre- and postdeployment data. We used
      multiple logistic regression to examine the role of killing-related exposures,
      after controlling for general combat and other suicide risks, and examined
      interactions between killing and other suicide vulnerability factors. RESULTS:
      Killing-related exposure approximately doubled the risk of MTSI in the cross
      sectional multivariate model (Adjusted Odds Ratio [AOR] = 1.87; CI = 1.26-2.78)
      and the longitudinal model (AOR = 2.02; CI = 1.06-3.85), which also controlled
      for predeployment risks. Killing exposures further increased the MTSI risk
      associated with other suicide vulnerability factors, including depression (AOR =
      14.89 for depression and killing vs. AOR = 9.92 for depression alone), alcohol
      dependence (AOR = 5.63 for alcohol and killing vs. 1.91 for alcohol alone), and
      readjustment stress (AOR = 4.90 for stress and killing vs. 1.48 for stress
      alone). General combat exposure had no comparable effects. CONCLUSIONS: The
      findings underscore a need for assessment and treatment protocols that address
      the psychological effects of killing-related and other potentially "morally
      injurious" experiences among combat soldiers.

PMID- 27030032
TI  - Cardiovascular disease in the literature: A selection of recent original research
      papers.

PMID- 27030033
TI  - Insecticide susceptibility of natural populations of Anopheles coluzzii and
      Anopheles gambiae (sensu stricto) from Okyereko irrigation site, Ghana, West
      Africa.
AB  - BACKGROUND: The increasing spread of insecticide resistance in malaria vectors
      has been well documented across sub-Saharan Africa countries. The influence of
      irrigation on increasing vector resistance is poorly understood, and is critical
      to successful and ethical implementation of food security policies. This study
      investigated the insecticide resistance status of An. gambiae (s.l.) mosquitoes
      collected from the irrigated rice area of Okyereko, a village containing about 42
      hectares of irrigated field within an irrigation project plan in the Central
      Region of Ghana. Large amounts of insecticides, herbicides and fertilizers are
      commonly used in the area to boost the annual production of the rice. METHODS:
      Mosquito larvae were collected and adults were assayed from the F1 progeny. The
      resistance status, allele and genotype were characterized using WHO
      susceptibility testing and PCR methods respectively. RESULTS: The An. gambiae
      (s.l.) populations from Okyereko are highly resistant to DDT and pyrethroid
      insecticides, with possible involvement of metabolic mechanisms including the
      elevation of P450 and GST enzyme as well as P-gp activity. The population was
      mostly composed of An. coluzzii specimens (more than 96 %) with kdr and ace-1
      frequencies of 0.9 and 0.2 %, respectively. CONCLUSION: This study brings
      additional information on insecticide resistance and the characterization of An.
      gambiae (s.l.) mosquitoes from Okyereko, which can be helpful in decision making
      for vector control programmes in the region.

PMID- 27030036
TI  - Erratum to: Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent
      pathway by 4-O-methyl-ascochlorin in leukemia cells.

PMID- 27030035
TI  - Health-care availability, preference, and distance for women in urban Bo, Sierra
      Leone.
AB  - OBJECTIVES: To examine the diversity of the health-care providers in urban Bo,
      Sierra Leone, identify the types of health-care facilities preferred by women for
      fevers, and analyze the road network distances from homes to preferred health
      care providers. METHODS: A population-based random sampling method was used to
      recruit 2419 women from Bo. A geographic information system was used to measure
      the road distance from each woman's home to her preferred provider. RESULTS:
      Preferred health-care providers for acute febrile illnesses (commonly referred to
      as "malaria" in the study communities) were hospitals (62.3 %), clinics (12.6 %),
      and pharmacies (12.4 %). Participants lived a median distance of 0.6 km from the
      nearest provider, but on average each woman lived 2.2 km one-way from her
      preferred provider. Women living farther from the city center had preferred
      providers significantly farther from home than women living downtown.
      CONCLUSIONS: The diverse health-care marketplace in Bo allows women to select
      clinical facilities from across the city. Most women prefer a malaria care
      provider farther from home than they could comfortably walk when ill.

PMID- 27030037
TI  - Viewpoint: taking into account risks of random errors when analysing multiple
      outcomes in systematic reviews.

PMID- 27030038
TI  - Neutral glycans from sandfish skin can reduce friction of polymers.
AB  - The lizardScincus scincus, also known as sandfish, can move through aeolian
      desert sand in a swimming-like manner. A prerequisite for this ability is a
      special integument, i.e. scales with a very low friction for sand and a high
      abrasion resistance. Glycans in the scales are causally related to the low
      friction. Here, we analysed the glycans and found that neutral glycans with five
      to nine mannose residues are important. If these glycans were covalently bound to
      acrylic polymers like poly(methyl methacrylate) or acrylic car coatings at a
      density of approximately one molecule per 4 nm2, friction for and adhesion of
      sand particles could be reduced to levels close to those observed with sandfish
      scales. This was also found true, if the glycans were isolated from sources other
      than sandfish scales like plants such as almonds or mistletoe. We speculate that
      these neutral glycans act as low density spacers separating sand particles from
      the dense scales thereby reducing van der Waals forces. 

PMID- 27030040
TI  - Correction to 'Evolving random fractal Cantor superlattices for the infrared
      using a genetic algorithm'.

PMID- 27030039
TI  - Modelling the seasonality of Lyme disease risk and the potential impacts of a
      warming climate within the heterogeneous landscapes of Scotland.
AB  - Lyme disease is the most prevalent vector-borne disease in the temperate Northern
      Hemisphere. The abundance of infected nymphal ticks is commonly used as a Lyme
      disease risk indicator. Temperature can influence the dynamics of disease by
      shaping the activity and development of ticks and, hence, altering the contact
      pattern and pathogen transmission between ticks and their host animals. A
      mechanistic, agent-based model was developed to study the temperature-driven
      seasonality of Ixodes ricinus ticks and transmission of Borrelia burgdorferi
      sensu lato across mainland Scotland. Based on 12-year averaged temperature
      surfaces, our model predicted that Lyme disease risk currently peaks in autumn,
      approximately six weeks after the temperature peak. The risk was predicted to
      decrease with increasing altitude. Increases in temperature were predicted to
      prolong the duration of the tick questing season and expand the risk area to
      higher altitudinal and latitudinal regions. These predicted impacts on tick
      population ecology may be expected to lead to greater tick-host contacts under
      climate warming and, hence, greater risks of pathogen transmission. The model is
      useful in improving understanding of the spatial determinants and system
      mechanisms of Lyme disease pathogen transmission and its sensitivity to
      temperature changes.

PMID- 27030041
TI  - Model-based reconstruction of an epidemic using multiple datasets: understanding
      influenza A/H1N1 pandemic dynamics in Israel.
AB  - Intensified surveillance during the 2009 A/H1N1 influenza pandemic in Israel
      resulted in large virological and serological datasets, presenting a unique
      opportunity for investigating the pandemic dynamics. We employ a conditional
      likelihood approach for fitting a disease transmission model to virological and
      serological data, conditional on clinical data. The model is used to reconstruct
      the temporal pattern of the pandemic in Israel in five age-groups and evaluate
      the factors that shaped it. We estimate the reproductive number at the beginning
      of the pandemic to beR= 1.4. We find that the combined effect of varying absolute
      humidity conditions and school vacations (SVs) is responsible for the infection
      pattern, characterized by three epidemic waves. Overall attack rate is estimated
      at 32% (28-35%) with a large variation among the age-groups: the highest attack
      rates within school children and the lowest within the elderly. This pattern of
      infection is explained by a combination of the age-group contact structure and
      increasing immunity with age. We assess that SVs increased the overall attack
      rates by prolonging the pandemic into the winter. Vaccinating school children
      would have been the optimal strategy for minimizing infection rates in all age
      groups. 

PMID- 27030042
TI  - Hummingbirds control turning velocity using body orientation and turning radius
      using asymmetrical wingbeat kinematics.
AB  - Turning in flight requires reorientation of force, which birds, bats and insects
      accomplish either by shifting body position and total force in concert or by
      using left-right asymmetries in wingbeat kinematics. Although both mechanisms
      have been observed in multiple species, it is currently unknown how each is used
      to control changes in trajectory. We addressed this problem by measuring body and
      wingbeat kinematics as hummingbirds tracked a revolving feeder, and estimating
      aerodynamic forces using a quasi-steady model. During arcing turns, hummingbirds
      symmetrically banked the stroke plane of both wings, and the body, into turns,
      supporting a body-dependent mechanism. However, several wingbeat asymmetries were
      present during turning, including a higher and flatter outer wingtip path and a
      lower more deviated inner wingtip path. A quasi-steady analysis of arcing turns
      performed with different trajectories revealed that changes in radius were
      associated with asymmetrical kinematics and forces, and changes in velocity were
      associated with symmetrical kinematics and forces. Collectively, our results
      indicate that both body-dependent and -independent force orientation mechanisms
      are available to hummingbirds, and that these kinematic strategies are used to
      meet the separate aerodynamic challenges posed by changes in velocity and turning
      radius. 

PMID- 27030043
TI  - Insect-computer hybrid legged robot with user-adjustable speed, step length and
      walking gait.
AB  - We have constructed an insect-computer hybrid legged robot using a living beetle
      (Mecynorrhina torquata; Coleoptera). The protraction/retraction and
      levation/depression motions in both forelegs of the beetle were elicited by
      electrically stimulating eight corresponding leg muscles via eight pairs of
      implanted electrodes. To perform a defined walking gait (e.g., gallop), different
      muscles were individually stimulated in a predefined sequence using a
      microcontroller. Different walking gaits were performed by reordering the applied
      stimulation signals (i.e., applying different sequences). By varying the duration
      of the stimulation sequences, we successfully controlled the step frequency and
      hence the beetle's walking speed. To the best of our knowledge, this paper
      presents the first demonstration of living insect locomotion control with a user
      adjustable walking gait, step length and walking speed.

PMID- 27030044
TI  - Lysophosphatidic Acid (LPA) Receptor 3-Mediated LPA Signal Transduction Pathways:
      A Possible Relationship with Early Development of Peri-Implantation Porcine
      Conceptus.
AB  - Lysophosphatidic acid (LPA) is a phospholipid with a variety of fatty acyl groups
      that mediates diverse biological effects on various types of cells through
      specific G protein-coupled receptors. LPA appears to play a significant role in
      many reproductive processes, including luteolysis, implantation, and
      placentation. Our previous study in pigs demonstrated that LPA and the LPA
      receptor system are present at the maternal-conceptus interface and that LPA
      increases uterine endometrial expression of prostaglandin-endoperoxide synthase 2
      (PTGS2) through LPA receptor 3 (LPAR3). However, the role of LPA in conceptuses
      during early pregnancy has not been determined. Therefore, this study examined
      the effects of LPA in cell proliferation, migration, and activation of the
      intracellular signaling pathway in porcine conceptuses by using an established
      porcine trophectoderm (pTr) cell line isolated from Day 12 conceptuses. All
      examined LPA species with various fatty acid lengths increased proliferation and
      migration of pTr cells as the dosage increased. Immunoblot analyses found that
      LPA activated intracellular signaling molecules, extracellular signal-regulated
      kinase 1/2 (ERK1/2), ribosomal protein S6 kinase 90 kDa (P90RSK), ribosomal
      protein S6 (RPS6), and P38 in pTr cells. Furthermore, LPA increased expression of
      PTGS2 and urokinase-type plasminogen activator (PLAU), and the LPA-induced
      increases in PTGS2 and PLAU expression were inhibited by LPAR3 siRNA.
      Collectively, these results showed that LPA promotes proliferation, migration,
      and differentiation of pTr cells by activating the ERK1/2-P90RSK-RPS6 and P38
      pathways, indicating that the LPA-LPAR3 system may be involved in the development
      of trophoblast during early pregnancy in pigs.

PMID- 27030045
TI  - High-Fat Diet Causes Subfertility and Compromised Ovarian Function Independent of
      Obesity in Mice.
AB  - Excess calorie consumption, particularly of a diet high in fat, is a risk factor
      for both obesity and reproductive disorders. Animal model studies indicate that
      elevated dietary fat can influence some reproductive functions independent of
      obesity. In the current study we sought to determine whether a high-fat diet
      (HFD) impacts ovarian function, long-term fertility, and local and systemic
      markers of inflammation independent of obesity. Five-week-old mice were fed
      either low-fat diet (control group-LF-Ln) or HFD for 10 wk and were divided based
      on body weight into high-fat obese (HF-Ob: >25 g) and high-fat lean (HF-Ln: <22
      g). Ovaries were collected to assess ovarian follicles and to determine the
      degree of local inflammation. Serum proinflammatory cytokines were also measured.
      A group of animals was followed for breeding trials for 5 mo while being exposed
      to LFD or HFD. We found that both 10-wk and 32-wk exposure to HFD resulted in
      depleted primordial follicles regardless of obesity phenotype. Macrophage counts
      revealed increased tissue inflammation in the ovary independent of obesity. In
      addition, serum proinflammatory cytokines were increased in HF-Ln and HF-Ob in
      comparison to LF-Ln mice. Moreover, HFD had a sustained effect on litter
      production rate and number of pups per litter regardless of obese phenotype. This
      study describes for the first time that exposure to HFD causes significant
      reduction in primordial follicles, compromised fertility, produced higher
      proinflammatory cytokine levels, and increased ovarian macrophage infiltration,
      independent of obesity. The negative effects of HFD on primordial follicles may
      be mediated by increased tissue inflammation.

PMID- 27030046
TI  - Adiponectin Inhibits Nutrient Transporters and Promotes Apoptosis in Human
      Villous Cytotrophoblasts: Involvement in the Control of Fetal Growth.
AB  - The placenta exchanges nutrients between the mother and the fetus and requires a
      constant abundant energy supply. Adiponectin (a cytokine produced primarily by
      adipose tissue) controls glucose and lipid homeostasis. It is well-known that
      maternal serum adiponectin levels are inversely related to birth weight,
      suggesting that adiponectin has a negative effect on fetal growth. This effect
      appears to be related to the control of nutrient transporters in human placenta.
      However, the underlying molecular mechanisms have not yet been characterized. In
      the present work, we studied adiponectin's direct effect on human primary
      cytotrophoblasts from first-trimester placenta. Our result showed that in
      placental cells, adiponectin 1) inhibits the expression of the major glucose
      transporters (GLUT1 and GLUT12) and sodium-coupled neutral amino acid
      transporters (SNAT1, SNAT2, and SNAT4), 2) enhances total ATP production but
      decreases lactate production, 3) inhibits mitochondrial biogenesis and function,
      and 4) stimulates cell death by enhancing the expression of the pro-apoptotic B
      cell lymphoma-2 (BCL-2)-associated X protein (BAX) and tumor protein P53 (TP53)
      gene expression and inducing the caspase activity. Small-interfering RNA
      mediating the down-regulation of adiponectin receptors (ADIPOR1 and ADIPOR2) was
      used to demonstrate that adiponectin effects on placental nutrient transport and
      apoptosis seemed to be essentially mediated by these specific receptors. Taken as
      a whole, these results strongly suggest that adiponectin regulates human
      placental function by limiting nutrient transporter expression and inducing
      apoptosis. These findings may help us to better understand adiponectin's role in
      placental pathologies such as intrauterine growth restriction, which is
      characterized by fetal weight loss and drastic apoptosis of placental cells.

PMID- 27030047
TI  - Influence of premorbid BMI on clinical characteristics at presentation of
      adolescent girls with eating disorders.
AB  - BACKGROUND: Considering the prevalence of obesity in society it can be expected
      that some adolescents with an eating disorder (ED) start weight loss from an
      overweight and present at a near-normal weight. Presently, the influence of
      premorbid BMI on clinical characteristics of adolescent girls presenting with an
      ED has ben studied. METHOD: Premorbid growth charts were available for 275
      postmenarcheal adolescent girls presenting with an ED (anorexia nervosa = 27,
      (subthreshold) bulimia nervosa = 9, restrictive EDNOS = 239). Initial assessment
      included measurement of weight and length, physical examination, blood sampling
      and administration of the Eating Disorder Examination-Questionnaire youth version
      (EDE-Q). RESULTS: Despite greater weight loss girls with a high premorbid body
      mass index (BMI) had a higher BMI at presentation compared to those with a lower
      premorbid BMI. Although not underweight some presented with clinical and
      laboratory signs of starvation. These signs were related to not only low BMI but
      also to rapid and large weight loss. Their EDE-Q scores did not differ from those
      of girls who presented with an underweight. CONCLUSION: Girls with a restrictive
      ED and premorbid overweight may present with a near-normal BMI. They can
      nevertheless be medically compromised and have eating disturbed cognitions at the
      level of underweight girls. They should not be regarded as having a less severe
      ED but merit full assessment and a start of treatment.

PMID- 27030048
TI  - Cross-linked versus conventional polyethylene for total knee arthroplasty: a meta
      analysis.
AB  - BACKGROUND: Highly cross-linked polyethylene (HXLPE) has been reported as an
      effective material for decreasing polyethylene wear and osteolysis in total knee
      arthroplasty (TKA). Because no single study to date has been large enough to
      definitively determine the benefit of HXLPE in TKA, we conducted a meta-analysis
      to pool the results from randomized controlled trials (RCTs) and non-RCTs to make
      such a determination. METHODS: Potential candidate articles were identified by
      searching the Cochrane Library, Medline (1966-2015.10), PubMed (1966-2015.10),
      Embase (1980-2015.10), ScienceDirect (1985-2015.10), and other databases. "Gray
      studies" were identified from the included articles' reference lists. Pooled data
      were analyzed using RevMan 5.1. RESULTS: Three RCTs and three non-RCTs were
      included in the meta-analysis. There were no significant differences between the
      groups in the total number of reoperations (P = 0.11), reoperations for
      prosthesis loosening (P = 0.08), radiolucent line (P = 0.20), osteolysis (P =
      0.38), prosthesis loosening (P = 0.10), and mechanical failures related to the
      tibial polyethylene (P = 1.00). Similarly, no significant differences between the
      two groups were found in postoperative total knee score (P = 0.18) or functional
      score (P = 0.23). CONCLUSIONS: The meta-analysis showed that compared with
      conventional polyethylene, HXLPE did not improve the clinical and radiographic
      outcomes in mid-term follow-up after TKA. Additional high-quality multicenter
      prospective RCTs with good design, large study populations and long-term follow
      up will be necessary to further clarify the effect of HXLPE in TKA.

PMID- 27030049
TI  - Transcriptome analysis of the painted lady butterfly, Vanessa cardui during wing
      color pattern development.
AB  - BACKGROUND: Butterfly wing color patterns are an important model system for
      understanding the evolution and development of morphological diversity and animal
      pigmentation. Wing color patterns develop from a complex network composed of
      highly conserved patterning genes and pigmentation pathways. Patterning genes are
      involved in regulating pigment synthesis however the temporal expression dynamics
      of these interacting networks is poorly understood. Here, we employ next
      generation sequencing to examine expression patterns of the gene network
      underlying wing development in the nymphalid butterfly, Vanessa cardui. RESULTS:
      We identified 9, 376 differentially expressed transcripts during wing color
      pattern development, including genes involved in patterning, pigmentation and
      gene regulation. Differential expression of these genes was highest at the pre
      ommochrome stage compared to early pupal and late melanin stages. Overall, an
      increasing number of genes were down-regulated during the progression of wing
      development. We observed dynamic expression patterns of a large number of pigment
      genes from the ommochrome, melanin and also pteridine pathways, including
      contrasting patterns of expression for paralogs of the yellow gene family.
      Surprisingly, many patterning genes previously associated with butterfly pattern
      elements were not significantly up-regulated at any time during pupation,
      although many other transcription factors were differentially expressed. Several
      genes involved in Notch signaling were significantly up-regulated during the pre
      ommochrome stage including slow border cells, bunched and pebbles; the function
      of these genes in the development of butterfly wings is currently unknown. Many
      genes involved in ecdysone signaling were also significantly up-regulated during
      early pupal and late melanin stages and exhibited opposing patterns of expression
      relative to the ecdysone receptor. Finally, a comparison across four butterfly
      transcriptomes revealed 28 transcripts common to all four species that have no
      known homologs in other metazoans. CONCLUSIONS: This study provides a
      comprehensive list of differentially expressed transcripts during wing
      development, revealing potential candidate genes that may be involved in
      regulating butterfly wing patterns. Some differentially expressed genes have no
      known homologs possibly representing genes unique to butterflies. Results from
      this study also indicate that development of nymphalid wing patterns may arise
      not only from melanin and ommochrome pigments but also the pteridine pigment
      pathway.

PMID- 27030050
TI  - High expression of alpha-synuclein in damaged mitochondria with PLA2G6
      dysfunction.
AB  - To clarify the role of alpha-synuclein (alphaSyn) in neuronal membrane
      remodeling, we analyzed the expression of alphaSyn in neurons with a dysfunction
      of PLA2G6, which is indispensable for membrane remodeling.
      alphaSyn/phosphorylated-alphaSyn (PalphaSyn) distribution and neurodegeneration
      were quantitatively estimated in PLA2G6-knockout (KO) mice, which demonstrate
      marked mitochondrial membrane degeneration. We also assessed the relationship
      between alphaSyn deposits and mitochondria in brain tissue from patients with
      PLA2G6-associated neurodegeneration (PLAN) and Parkinson's disease (PD), and
      quantitatively examined Lewy bodies (LBs) and neurons. The expression level of
      alphaSyn was elevated in PLA2G6-knockdown cells and KO mouse neurons. Strong
      PalphaSyn expression was observed in neuronal granules in KO mice before onset of
      motor symptoms. The granules were mitochondrial outer membrane protein (TOM20)
      positive. Ultramicroscopy revealed that PalphaSyn-positive granules were
      localized to mitochondria with degenerated inner membranes. After symptom onset,
      TOM20-positive granules were frequently found in ubiquitinated spheroids, where
      PalphaSyn expression was low. Axons were atrophic, but the neuronal loss was not
      evident in KO mice. In PLAN neurons, small PalphaSyn-positive inclusions with a
      TOM20-positive edge were frequently observed and clustered into LBs. The surfaces
      of most LBs were TOM20-positive in PLAN and TOM20-negative in PD brains. The high
      proportion of LB-bearing neurons and the preserved neuronal number in PLAN
      suggested long-term survival of LB-bearing neurons. Elevated expression of
      alphaSyn/PalphaSyn in mitochondria appears to be the early response to PLA2G6
      deficiency in neurons. The strong affinity of alphaSyn for damaged mitochondrial
      membranes may promote membrane stabilization of mitochondria and neuronal
      survival in neurons. 

PMID- 27030052
TI  - Understanding doctors' attitudes towards self-disclosure of mental ill health.
AB  - BACKGROUND: Understanding of doctors' attitudes towards disclosing their own
      mental illness has improved but assumptions are still made. AIMS: To investigate
      doctors' attitudes to disclosing mental illness and the obstacles and enablers to
      seeking support. METHODS: An anonymous, UK-wide online survey of doctors with and
      without a history of mental illness. The main outcome measure was likelihood of
      workplace disclosure of mental illness. RESULTS: In total, 1954 doctors responded
      and 60% had experienced mental illness. There was a discrepancy between how
      doctors think they might behave and how they actually behaved when experiencing
      mental illness. Younger doctors were least likely to disclose, as were trainees.
      There were multiple obstacles which varied across age and training grade.
      CONCLUSIONS: For all doctors, regardless of role, this study found that what they
      think they would do is different to what they actually do when they become
      unwell. Trainees, staff and associate speciality doctors and locums appeared most
      vulnerable, being reluctant to disclose mental ill health. Doctors continued to
      have concerns about disclosure and a lack of care pathways was evident. Concerns
      about being labelled, confidentiality and not understanding the support
      structures available were identified as key obstacles to disclosure. Addressing
      obstacles and enablers is imperative to shape future interventions.

PMID- 27030051
TI  - Texting Adolescents in Repeat DKA and Their Caregivers.
AB  - BACKGROUND: Text message interventions are feasible, preferable, and sometimes
      effective for youth with diabetes. However, few, if any studies, have examined
      the personalized use of text messages with youth repeatedly hospitalized for
      diabetic ketoacidosis (DKA) and their caregivers. This study characterizes the
      use of personalized text messages in Novel Interventions in Children's Healthcare
      (NICH). METHODS: Approximately 2 months of text messages sent to youth with
      repeat DKA and their caregivers were logged regarding the following text
      characteristics: (1) content, (2) intervention type, (3) timing, and (4)
      recipient characteristics. RESULTS: NICH interventionists sent 2.3 and 1.5 texts
      per day to patients and caregivers, respectively. Approximately 59% of outgoing
      texts occurred outside of typical business hours, and roughly 68% of texts
      contained some form of support and/or encouragement. The relation between type of
      intended intervention and day/time of text was significant, chi(2)(2, N = 5,808)
      = 266.93, P < .001. Interventionists were more likely to send behavioral
      intervention text messages outside of business hours, whereas they were more
      likely to send care coordination and case management text messages during
      business hours. CONCLUSIONS: To our knowledge, this is the first study to
      specifically categorize and describe the personalized use of text messages with
      youth repeatedly hospitalized for DKA and their caregivers. Findings indicate
      that a promising treatment program for these youth frequently used text
      interventions to deliver praise and encouragement to patients and caregivers
      alike, often outside of typical business hours, and tailored text content based
      on patient and caregiver characteristics.

PMID- 27030053
TI  - Analysis of effects of a new environmental pollutant, bisphenol A, on antioxidant
      systems in soybean roots at different growth stages.
AB  - Bisphenol A (BPA) is an important industrial raw material. Because of its
      widespread use and increasing release into environment, BPA has become a new
      environmental pollutant. Previous studies about BPA's effects in plants focus on
      a certain growth stage. However, the plant's response to pollutants varies at
      different growth stages. Therefore, in this work, BPA's effects in soybean roots
      at different growth stages were investigated by determining the reactive oxygen
      species levels, membrane lipid fatty acid composition, membrane lipid
      peroxidation, and antioxidant systems. The results showed that low-dose BPA
      exposure slightly caused membrane lipid peroxidation but didn't activate
      antioxidant systems at the seedling stage, and this exposure did not affect above
      process at other growth stages; high-dose BPA increased reactive oxygen species
      levels and then caused membrane lipid peroxidation at all growth stages although
      it activated antioxidant systems, and these effects were weaker with prolonging
      the growth stages. The recovery degree after withdrawal of BPA exposure was
      negatively related to BPA dose, but was positively related to growth stage. Taken
      together, the effects of BPA on antioxidant systems in soybean roots were
      associated with BPA exposure dose and soybean growth stage. 

PMID- 27030054
TI  - Acute effect of rosiglitazone on relaxation responses in hypercholesterolemic
      corpus cavernosum.
AB  - Thiazolidinediones (TZDs) improve vascular endothelial dysfunction through non
      genomic effects of peroxisomal proliferator-activated receptor gamma. This study
      investigated the acute effect of one of the TZD, rosiglitazone, on endothelium
      dependent relaxation response of corpus cavernosum (CC) in hypercholesterolemic
      rabbits. New Zealand rabbits were divided into two groups randomly as control and
      cholesterol groups. Hypercholesterolemia was induced by feeding rabbits with 2%
      cholesterol diet (w/w) for 6 weeks. Endothelium-dependent and -independent
      relaxation response of CC were evaluated in the presence of rosiglitazone by
      organ bath studies with cumulative doses of acetylcholine (Ach) and sodium
      nitroprusside (SNP). Maximal relaxation (Emax) response to Ach significantly
      decreased owing to hypercholesterolemia in CC tissues. However, in vitro
      incubation of rosiglitazone with different concentrations (0.1, 1 and 10 MUm) did
      not improve the Ach-dependent Emax responses in hypercholesterolemic rabbit CC.
      Surprisingly, rosiglitazone caused a significant decrease in Ach-dependent
      relaxation in healthy CC. Emax responses to SNP did not differ in the presence of
      rosiglitazone in both the control and hypercholesterolemic groups. Rosiglitazone
      does not improve hypercholesterolemia-induced endothelial dysfunction in CC
      tissues while it dose-dependently impairs endothelium-dependent relaxation in
      healthy CC tissue. 

PMID- 27030055
TI  - Surgical treatment of Peyronie's disease with small intestinal submucosa graft
      patch.
AB  - The objective of the study was to report our results using a porcine small
      intestinal submucosa graft (Surgisis ES, Cook Medical) for tunica albuginea
      substitution after plaque incision. We retrospectively evaluated patients
      surgically treated at our institution for Peyronie's disease (PD) by means of
      plaque incision and porcine small intestinal submucosa grafting (Surgisis)
      between 2009 and 2013. At the same time a literature review was conducted,
      searching for similar reports and results. Forty-four patients were identified
      who had been diagnosed with PD between 2009 and the beginning of 2013, and had
      been treated with corporoplasty, plaque incision and grafting with Surgisis for a
      severe curvature of the penis. Curvature of the penis was dorsal in 40 patients
      (90%) and laterally on the right in 4 patients (10%). Mean duration of surgery
      was 165 min (range 90-200). Mean size of the graft was 6.5 cm(2) and the mean
      follow-up was 19.2 months (range 11-48). In patients with severe curvature of the
      penis due to PD and the need for corporoplasty with plaque incision and graft
      placement, Surgisis represents a good option with a low risk of complications,
      below the rate described with previously investigated graft tissues. 

PMID- 27030056
TI  - Up-to-down rectal resection with total mesorectal excision through single
      incision laparoscopy - a video vignette.

PMID- 27030057
TI  - Dangerous (toxic) atmospheres in UK wood pellet and wood chip fuel storage.
AB  - There is growing use of wood pellet and wood chip boilers in the UK. Elsewhere
      fatalities have been reported, caused by carbon monoxide poisoning following
      entry into wood pellet storage areas. The aim of this work was to obtain
      information on how safely these two fuels are being stored in the UK. Site visits
      were made to six small-scale boiler systems and one large-scale pellet warehouse,
      to assess storage practice, risk management systems and controls, user knowledge,
      and potential for exposure to dangerous atmospheres. Real time measurements were
      made of gases in the store rooms and during laboratory tests on pellets and
      chips. Volatile organic compounds (VOCs) emitted and the microbiological content
      of the fuel was also determined. Knowledge of the hazards associated with these
      fuels, including confined space entry, was found to be limited at the smaller
      sites, but greater at the large pellet warehouse. There has been limited risk
      communication between companies supplying and maintaining boilers, those
      manufacturing and supplying fuel, and users. Risk is controlled by restricting
      access to the store rooms with locked entries; some store rooms have warning
      signs and carbon monoxide alarms. Nevertheless, some store rooms are accessed for
      inspection and maintenance. Laboratory tests showed that potentially dangerous
      atmospheres of carbon monoxide and carbon dioxide, with depleted levels of oxygen
      may be generated by these fuels, but this was not observed at the sites visited.
      Unplanned ventilation within store rooms was thought to be reducing the build-up
      of dangerous atmospheres. Microbiological contamination was confined to wood
      chips.

PMID- 27030058
TI  - Bioengineering of Tobacco Mosaic Virus to Create a Non-Infectious Positive
      Control for Ebola Diagnostic Assays.
AB  - The 2014 Ebola epidemic is the largest to date. There is no cure or treatment for
      this deadly disease; therefore there is an urgent need to develop new diagnostics
      to accurately detect Ebola. Current RT-PCR assays lack sensitive and reliable
      positive controls. To address this critical need, we devised a bio-inspired
      positive control for use in RT-PCR diagnostics: we encapsulated scrambled Ebola
      RNA sequences inside of tobacco mosaic virus to create a biomimicry that is non
      infectious, but stable, and could therefore serve as a positive control in Ebola
      diagnostic assays. Here, we report the bioengineering and validation of this
      probe. 

PMID- 27030059
TI  - Advantages of contrast-enhanced ultrasonography over computed tomography for the
      detection of persistent type II endoleak after embolization: A case report.
AB  - The aim of this case report is to describe the use of contrast-enhanced
      ultrasonography in the detection of a type II endoleak after prior embolization
      with Onyx. A 74-year-old male patient with hypertension previously underwent
      endovascular repair of a 7.1-cm infrarenal aortic aneurysm. CT angiography
      surveillance revealed a type II endoleak associated with aneurysm sac expansion.
      Selective transarterial embolization of the endoleak was performed, but it was
      not possible to detect the persistent endoleak using CT angiography because of
      image artifacts caused by Onyx. Contrast-enhanced ultrasonography enabled us to
      detect the persistent endoleak in this patient. (c) 2016 Wiley Periodicals, Inc.
      J Clin Ultrasound 44:522-526, 2016. 

PMID- 27030061
TI  - Managing the burden of sickle-cell disease in Africa.

PMID- 27030060
TI  - Haematology: a critical field in health.

PMID- 27030062
TI  - Refining pathological diagnoses in lymphoid malignancies.

PMID- 27030063
TI  - Correction to Lancet Haematol 2014; 1: e17-27.

PMID- 27030064
TI  - Prognostic value of PET-CT after first-line therapy in patients with follicular
      lymphoma: a pooled analysis of central scan review in three multicentre studies.
AB  - BACKGROUND: The value of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET) imaging in
      response assessment after first-line rituximab chemotherapy for follicular
      lymphoma has been documented. We analysed the application of the five-point
      Deauville scale (5PS; used to score FDG uptake on PET images) in a large cohort
      derived from three studies, to assess the correlation between post-induction PET
      status and survival in patients with follicular lymphoma. METHODS: In this pooled
      analysis, we used data from three multicentre prospective studies of first-line
      rituximab chemotherapy for patients with high-tumour-burden follicular lymphoma
      (the PRIMA study, the PET-Folliculaire study, and the Fondazione Italiana Linfomi
      FOLL05 study). Patients included in this analysis received at least six cycles of
      rituximab and chemotherapy before response assessment with conventional contrast
      enhanced CT and PET low-dose CT (PET). We included only patients who had a PET
      scan within 3 months of the last dose of induction rituximab. Patient data,
      including conventional CT-based response assessment, were recorded for all
      patients undergoing PET review. Scans undergoing central PET review were scored
      independently by three reviewers according to the 5PS. The primary endpoints were
      progression-free survival and overall survival according to the 5PS score of post
      induction PET scan (ie, positive [>=4 points] or negative [<4 points]), analysed
      in the central review population. FINDINGS: Between Dec 24, 2004, and Sept 22,
      2010, 439 of the patients enrolled in the three studies underwent local PET
      assessment, 246 of whom had centrally reviewed post-induction scans. 41 (17%) of
      246 patients had a positive post-induction PET scan according to a cutoff of 4 or
      higher on the 5PS, with substantial reporter concordance. With a median follow-up
      of 54.8 months (IQR 39.7-68.5; range 7.7-90.1), the hazard ratio (HR) for
      progression-free survival for patients with a positive PET scan versus those with
      a negative PET scan was 3.9 (95% CI 2.5-5.9; p<0.0001), and for overall survival
      was 6.7 (2.4-18.5; p=0.0002). For patients with a positive PET scan, 23.2% (95%
      CI 11.1-37.9) of patients were progression free at 4 years compared with 63.4%
      (55.9-70.0) of those who had a negative PET scan (p<0.0001); 4-year overall
      survival was 87.2% (95% CI 71.9-94.5) versus 97.1% (93.2-98.8), respectively
      (p<0.0001). Conventional CT-based response (ie, complete response or unconfirmed
      complete response vs partial response) was weakly predictive of progression-free
      survival (HR 1.7 [95% CI 1.1-2.5]; p=0.017). INTERPRETATION: PET-CT rather than
      contrast-enhanced CT scanning should be considered as a new standard for response
      assessment of follicular lymphoma in clinical practice, and could help guide
      response-adapted therapy. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte
      (Paris, France), now LYSA (Lymphoma Study Association), Direction de la Recherche
      Clinique de l'Assistance Publique-Hopitaux de Paris, Fondazione Italiana Linfomi,
      and the Italian Ministry of Health.

PMID- 27030065
TI  - PET-CT restaging: a surrogate for follicular lymphoma?

PMID- 27030066
TI  - Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of
      symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and
      EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials.
AB  - BACKGROUND: Patients with venous thromboembolism and cancer have a substantial
      risk of recurrent venous thromboembolism and bleeding during anticoagulant
      therapy. Although monotherapy with low-molecular-weight heparin is recommended in
      these patients, in clinical practice many patients with venous thromboembolism
      and cancer do not receive this treatment. We aimed to assess the efficacy and
      safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin
      followed by vitamin K antagonists, in the subgroup of patients with cancer
      enrolled in the EINSTEIN-DVT and EINSTEIN-PE randomised controlled trials.
      METHODS: We did a subgroup analysis of patients with active cancer (either at
      baseline or diagnosed during the study), a history of cancer, or no cancer who
      were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials. Eligible patients with
      deep-vein thrombosis (EINSTEIN-DVT) or pulmonary embolism (EINSTEIN-PE) were
      randomly assigned in a 1:1 ratio to receive rivaroxaban (15 mg twice daily for 21
      days, followed by 20 mg once daily) or standard therapy (enoxaparin 1.0 mg/kg
      twice daily and warfarin or acenocoumarol; international normalised ratio 2.0
      3.0). Randomisation with a computerised voice-response system was stratified
      according to country and intended treatment duration (3, 6, or 12 months). The
      prespecified primary efficacy and safety outcomes of both the trials and this
      subanalysis were symptomatic recurrent venous thromboembolism and clinically
      relevant bleeding, respectively. We did efficacy and mortality analyses in the
      intention-to-treat population, and bleeding analyses for time spent receiving
      treatment plus 2 days in the safety population (all patients who received at
      least one dose of study drug). The EINSTEIN-DVT and EINSTEIN-PE studies are
      registered at ClinicalTrials.gov, numbers NCT00440193 and NCT00439777. FINDINGS:
      In patients with active cancer (diagnosed at baseline or during treatment),
      recurrent venous thromboembolism occurred in 16 (5%) of 354 patients allocated to
      rivaroxaban and 20 (7%) of 301 patients allocated to enoxaparin and vitamin K
      antagonist (hazard ratio [HR] 0.67, 95% CI 0.35 to 1.30). Clinically relevant
      bleeding occurred in 48 (14%) of 353 patients receiving rivaroxaban and in 49
      (16%) of 298 patients receiving standard therapy (HR 0.80, 95% CI 0.54 to 1.20).
      Major bleeding occurred in eight (2%) of 353 patients receiving rivaroxaban and
      in 15 (5%) of 298 patients receiving standard therapy (HR 0.42, 95% CI 0.18 to
      0.99). The overall frequency of recurrent venous thromboembolism in patients with
      only a history of cancer (five [2%] of 233 patients in the rivaroxaban group vs
      five [2%] of 236 in the standard therapy group; HR 0.98, 95% CI 0.28-3.43) was
      similar to that of patients without cancer (65 [2%] of 3563 vs 70 [2%] of 3594,
      respectively; HR 0.93, 95% CI 0.66-1.30), but the frequency was increased in
      patients with active cancer at baseline (six [2%] of 258 vs eight [4%] of 204,
      respectively; HR 0.62, 95% CI 0.21-1.79) and most markedly increased in patients
      whose diagnosis of cancer was made during the study (ten [10%] of 96 vs 12 [12%]
      of 97, respectively; HR 0.80, 95% CI 0.34-1.88). The overall frequency of major
      bleeding in patients with only a history of cancer (one [<1%] patient in the
      rivaroxaban group vs four [2%] patients in the standard therapy group; HR 0.23,
      95% CI 0.03-2.06) was similar to that of patients without cancer (31 [1%] vs 53
      [1%], respectively; HR 0.58, 95% CI 0.37-0.91), but was increased in patients
      with active cancer at baseline (five [2%] vs eight [4%], respectively; HR 0.47,
      95% CI 0.15-1.45) and was highest in those with cancer diagnosed during the study
      (three [3%] vs seven [7%], respectively; HR 0.33, 95% CI 0.08-1.31).
      INTERPRETATION: In patients with active cancer and venous thromboembolism,
      rivaroxaban had similar efficacy to prevent recurrence of venous thromboembolism
      and reduced the number major bleeding events compared with treatment with
      enoxaparin and a vitamin K antagonist, although there was no difference between
      groups for clinically relevant bleeding. Based on these results, a head-to-head
      comparison of rivaroxaban with long-term low-molecular-weight heparin in patients
      with cancer is warranted. FUNDING: Bayer HealthCare Pharmaceuticals and Janssen
      Research & Development.

PMID- 27030067
TI  - Multiple myeloma: the puzzle is finally completed.

PMID- 27030068
TI  - Treating clots in cancer: moving closer to an answer?

PMID- 27030069
TI  - The athlete biological passport: haematology in sports.

PMID- 27030070
TI  - Factors that affect implementation of a nurse staffing directive: results from a
      qualitative multi-case evaluation.
AB  - AIM/S: To assess implementation of the Veterans Health Administration staffing
      methodology directive. BACKGROUND: In 2010 the Veterans Health Administration
      promulgated a staffing methodology directive for inpatient nursing units to
      address staffing and budget forecasting. DESIGN: A qualitative multi-case
      evaluation approach assessed staffing methodology implementation. METHODS: Semi
      structured telephone interviews were conducted from March - June 2014 with Nurse
      Executives and their teams at 21 facilities. Interviews focused on the budgeting
      process, implementation experiences, use of data, leadership support, and
      training. An implementation score was created for each facility using a 4-point
      rating scale. The scores were used to select three facilities (low, medium and
      high implementation) for more detailed case studies. RESULTS/FINDINGS: After
      analysing interview summaries, the evaluation team developed a four domain
      scoring structure: (1) integration of staffing methodology into budget
      development; (2) implementation of the Directive elements; (3) engagement of
      leadership and staff; and (4) use of data to support the staffing methodology
      process. The high implementation facility had leadership understanding and
      endorsement of staffing methodology, confidence in and ability to work with data,
      and integration of staffing methodology results into the budgeting process. The
      low implementation facility reported poor leadership engagement and little
      understanding of data sources and interpretation. CONCLUSION: Implementation
      varies widely across facilities. Implementing staffing methodology in facilities
      with complex and changing staffing needs requires substantial commitment at all
      organizational levels especially for facilities that have traditionally relied on
      historical levels to budget for staffing.

PMID- 27030071
TI  - 'Crystal Genes' in Metallic Liquids and Glasses.
AB  - We analyze the underlying structural order that transcends liquid, glass and
      crystalline states in metallic systems. A genetic algorithm is applied to search
      for the most common energetically favorable packing motifs in crystalline
      structures. These motifs are in turn compared to the observed packing motifs in
      the actual liquid or glass structures using a cluster-alignment method. Using
      this method, we have revealed the nature of the short-range order in Cu64Zr36
      glasses. More importantly, we identified a novel structural order in the Al90Sm10
      system. In addition, our approach brings new insight into understanding the
      origin of vitrification and describing mesoscopic order-disorder transitions in
      condensed matter systems. 

PMID- 27030072
TI  - Origin of distinct structural symmetry of the neopentane cation in the ground
      electronic state compared to the methane cation.
AB  - An ab initio quantum dynamics study has been performed to explore the distinct
      structural symmetry of C(CH3)4(+) in the ground electronic state compared to
      CH4(+). Additionally, the underlying details of the highly diffuse and complex
      vibronic structure of the first photoelectron band of C(CH3)4 have been
      investigated. Associated potential energy surfaces over the two-dimensional space
      of nuclear coordinates, subject to the T2? (e + t2) Jahn-Teller effect, are
      established from extensive electronic structure calculations and (then) the
      nuclear dynamics calculations are done on them via wave packet propagation
      including the nonadiabatic coupling of the three electronic sheets. The
      theoretical results are in good agreement with experimental observations. The JT
      stabilization energies due to T2?e, T2?t2 and T2? (e + t2) distortions in the
      X[combining tilde](2)T2 electronic manifold of C(CH3)4(+) illustrate that the
      highest stabilization occurs through the T2?t2-JT distortion (in the ground state
      of C(CH3)4(+)). However, CH4(+) gains such maximum stabilization due to T2? (e +
      t2)-JT distortion. From this novel result and applying the epikernel principle,
      we propose that the structural evolution of C(CH3)4(+) from Td to C3v minimum
      energy configuration occurs via JT active vibrations of t2 symmetry, whereas
      CH4(+) rearranges to the C2v structure through a combination of JT active e and
      t2 bending vibrations.

PMID- 27030073
TI  - Immunotherapy: Atezolizumab becomes POPLAR.

PMID- 27030074
TI  - New technology: Integrated approach to genetic profiling of blood cancers.

PMID- 27030075
TI  - Evaluation and management of pancreatic lesions in patients with von Hippel
      Lindau disease.
AB  - von Hippel-Lindau (VHL) disease is a heritable cancer-predisposition syndrome
      with multiorgan involvement. Pancreatic lesions are detected in approximately two
      thirds of patients with VHL disease at some point during their lifetime. In these
      patients, cystic pancreatic lesions are almost exclusively benign and, unless
      symptomatic, do not require surgical or endoscopic intervention; however, solid
      pancreatic lesions can often be recognized through imaging screens, and are
      commonly found to be nonfunctioning pancreatic neuroendocrine tumours (pNETs)
      with malignant potential. The natural history of these VHL-associated pNETs is
      variable, and lacks clinical or imaging features that predict disease progression
      or metastatic potential, and generally needs to be managed more conservatively
      than their sporadic counterparts. Treatment options for such lesions, which range
      from active surveillance to surgical intervention, can nevertheless be associated
      with considerable morbidity and even mortality. Of note, although several
      guidelines have been established for the management of tumours associated with
      VHL syndrome, none of these have specifically focused on pancreatic lesions.
      Thus, we aim to characterize the types of pancreatic lesions associated with VHL
      disease and their natural history, to identify particular lesions that
      necessitate treatment, and to define what forms of treatment should be
      undertaken.

PMID- 27030076
TI  - Immunotherapy: Clonal neoantigens and immune response: a balancing act.

PMID- 27030079
TI  - Validity and reliability of the NAB Naming Test.
AB  - OBJECTIVE: Confrontation naming is commonly assessed in neuropsychological
      practice, but few standardized measures of naming exist and those that do are
      susceptible to the effects of education and culture. The Neuropsychological
      Assessment Battery (NAB) Naming Test is a 31-item measure used to assess
      confrontation naming. Despite adequate psychometric information provided by the
      test publisher, there has been limited independent validation of the test.
      METHOD: In this study, we investigated the convergent and discriminant validity,
      internal consistency, and alternate forms reliability of the NAB Naming Test in a
      sample of adults (Form 1: n = 247, Form 2: n = 151) clinically referred for
      neuropsychological evaluation. RESULTS: Results indicate adequate-to-good
      internal consistency and alternate forms reliability. We also found strong
      convergent validity as demonstrated by relationships with other neurocognitive
      measures. We found preliminary evidence that the NAB Naming Test demonstrates a
      more pronounced ceiling effect than other commonly used measures of naming.
      CONCLUSIONS: To our knowledge, this represents the largest published independent
      validation study of the NAB Naming Test in a clinical sample. Our findings
      suggest that the NAB Naming Test demonstrates adequate validity and reliability
      and merits consideration in the test arsenal of clinical neuropsychologists.

PMID- 27030077
TI  - Treating cancer with selective CDK4/6 inhibitors.
AB  - Uncontrolled cellular proliferation, mediated by dysregulation of the cell-cycle
      machinery and activation of cyclin-dependent kinases (CDKs) to promote cell-cycle
      progression, lies at the heart of cancer as a pathological process. Clinical
      implementation of first-generation, nonselective CDK inhibitors, designed to
      inhibit this proliferation, was originally hampered by the high risk of toxicity
      and lack of efficacy noted with these agents. The emergence of a new generation
      of selective CDK4/6 inhibitors, including ribociclib, abemaciclib and
      palbociclib, has enabled tumour types in which CDK4/6 has a pivotal role in the
      G1-to-S-phase cell-cycle transition to be targeted with improved effectiveness,
      and fewer adverse effects. Results of pivotal phase III trials investigating
      palbociclib in patients with advanced-stage oestrogen receptor (ER)-positive
      breast cancer have demonstrated a substantial improvement in progression-free
      survival, with a well-tolerated toxicity profile. Mechanisms of acquired
      resistance to CDK4/6 inhibitors are beginning to emerge that, although unwelcome,
      might enable rational post-CDK4/6 inhibitor therapeutic strategies to be
      identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast
      cancer is challenging, and will likely require biomarkers that are predictive of
      a response, and the use of combination therapies in order to optimize CDK4/6
      targeting.

PMID- 27030080
TI  - Evaluating Battery-like Reactions to Harvest Energy from Salinity Differences
      using Ammonium Bicarbonate Salt Solutions.
AB  - Mixing entropy batteries (MEBs) are a new approach to generate electricity from
      salinity differences between two aqueous solutions. To date, MEBs have only been
      prepared from solutions containing chloride salts, owing to their relevance in
      natural salinity gradients created from seawater and freshwater. We hypothesized
      that MEBs could capture energy using ammonium bicarbonate (AmB), a thermolytic
      salt that can be used to convert waste heat into salinity gradients. We examined
      six battery electrode materials. Several of the electrodes were unstable in AmB
      solutions or failed to produce expected voltages. Of the electrode materials
      tested, a cell containing a manganese oxide electrode and a metallic lead
      electrode produced the highest power density (6.3 mW m(-2) ). However, this power
      density is still low relative to previously reported NaCl-based MEBs and heat
      recovery systems. This proof-of-concept study demonstrated that MEBs could indeed
      be used to generate electricity from AmB salinity gradients.

PMID- 27030078
TI  - Immunological off-target effects of imatinib.
AB  - Around 15 years ago, imatinib mesylate (Gleevec((r)) or Glivec((r)), Novartis,
      Switzerland) became the very first 'targeted' anticancer drug to be clinically
      approved. This drug constitutes the quintessential example of a successful
      precision medicine that has truly changed the fate of patients with Philadelphia
      chromosome-positive chronic myeloid leukaemia (CML) and gastrointestinal stromal
      tumours by targeting the oncogenic drivers of these diseases, BCR-ABL1 and KIT
      and/or PDGFR, mutations in which lead to gain of function of tyrosine kinase
      activities. Nonetheless, the aforementioned paradigm might not fully explain the
      clinical success of this agent in these diseases. Growing evidence indicates that
      the immune system has a major role both in determining the therapeutic efficacy
      of imatinib (and other targeted agents) and in restraining the emergence of
      escape mutations. In this Review, we re-evaluate the therapeutic utility of
      imatinib in the context of the anticancer immunosurveillance system, and we
      discuss how this concept might inform on novel combination regimens that include
      imatinib with immunotherapies.

PMID- 27030081
TI  - Haematuria is not a risk factor of hypertension or renal impairment in patients
      with haemophilia.
AB  - INTRODUCTION: An increased prevalence of hypertension has been reported in
      patients with haemophilia compared to the age-matched general population,
      although the causes were unclear. To date, there has been limited data
      implicating haemophilia-specific risk factors such as renal bleeding. AIM: This
      two-centre prospective cohort study aimed to assess the prevalence of
      gross/microscopic haematuria, and the associations between haematuria, blood
      pressure and renal function. METHODS: Of 135 adult males, with mild to severe
      haemophilia followed by the British Columbia and University of California San
      Diego Hemophilia Treatment Centers were included. Screening urinalysis and
      microscopy were performed during all routine visits. Haematuria was defined as
      history of gross haematuria or >3 red blood cells per high-power field on
      microscopy in the absence of urinary tract infections. Logistic regressions were
      used to examine the significance of haematuria and other potential hypertension
      risk factors. RESULTS: The prevalence of hypertension was 44%, of whom 31%
      achieved adequate blood pressure control. Despite the high prevalence of
      haematuria (34%), renal dysfunction was rare. On univariate analysis, age,
      diabetes, dyslipidemia and obesity were associated with hypertension. On
      multivariate analysis, only age remains as a significant predictor of
      hypertension. Haematuria was not associated with hypertension, renal
      insufficiency or haemophilia severity. CONCLUSION: In this cohort, hypertension
      and haematuria were prevalent while renal disease was rare. Haematuria was not
      associated with a diagnosis of hypertension or renal dysfunction. Larger
      prospective studies are needed to elucidate the mechanisms for increased
      prevalence of hypertension in haemophilia.

PMID- 27030082
TI  - Transurethral assistant transumbilical laparoendoscopic single-site radical
      prostatectomy.
AB  - The laparoendoscopic single-site (LESS) technique is the latest technical
      innovation in laparoscopic surgery to undergo exponential development in urology.
      This study undertaken to illustrate our initial experience LESS radical
      prostatectomy (RP) and analyze early outcomes. Nineteen patients diagnosed with
      prostate cancer underwent LESS-RP in our institute. The patients were divided
      into two groups: conventional LESS and transurethral assistant LESS.
      Preoperative, perioperative, postoperative, pathologic, and functional outcomes
      data were assessed. With the help of a transurethral assistant, the mean
      operation and anastomosis time were decreased markedly. No focal positive margins
      were encountered. No prostate-specific antigen recurrence was detected 1 month
      postoperatively. Complete continence recovery (no pad) was observed in 32% of the
      patients at 1 month after the operation. No intraoperative and postoperative
      complications were reported. LESS-RP is a feasible and effective surgical
      procedure for treatment of prostate cancer. Moreover, transurethral assistant
      LESS could reduce the difficulty of LESS-RP and shorten the operation time.

PMID- 27030083
TI  - Genomic predictors for treatment of late stage prostate cancer.
AB  - In spite of the development of new treatments for late stage prostate cancer,
      significant challenges persist to match individuals with effective targeted
      therapies. Genomic classification using high-throughput sequencing technologies
      has the potential to achieve this goal and make precision medicine a reality in
      the management of men with castrate-resistant prostate cancer. This chapter
      reviews some of the most recent studies that have resulted in significant
      progress in determining the landscape of somatic genomic alterations in this
      cohort and, more importantly, have provided clinically actionable information
      that could guide treatment decisions. This chapter reviews the current
      understanding of common alterations such as alterations of the androgen receptor
      and PTEN pathway, as well as ETS gene fusions and the growing importance of PARP
      inhibition. It also reviews recent studies that characterize the evolution to
      neuroendocrine tumors, which is becoming an increasingly important clinical
      problem. Finally, this chapter reviews recent innovative studies that
      characterize the compelling evolutionary history of lethal prostate cancer
      evidenced by polyclonal seeding and interclonal cooperation between metastasis
      and the importance of tumor clone dynamics measured serially in response to
      treatment. The genomic landscape of late stage prostate cancer is becoming better
      defined, and the prospect for assigning clinically actionable data to inform
      rationale treatment for individuals with this disease is becoming a reality. 

PMID- 27030084
TI  - Insurance coverage for male infertility care in the United States.
AB  - Infertility is a common condition experienced by many men and women, and
      treatments are expensive. The World Health Organization and American Society of
      Reproductive Medicine define infertility as a disease, yet private companies
      infrequently offer insurance coverage for infertility treatments. This is despite
      the clear role that healthcare insurance plays in ensuring access to care and
      minimizing the financial burden of expensive services. In this review, we assess
      the current knowledge of how male infertility care is covered by insurance in the
      United States. We begin with an appraisal of the costs of male infertility care,
      then examine the state insurance laws relevant to male infertility, and close
      with a discussion of why insurance coverage for male infertility is important to
      both men and women. Importantly, we found that despite infertility being
      classified as a disease and males contributing to almost half of all infertility
      cases, coverage for male infertility is often excluded from health insurance
      laws. Excluding coverage for male infertility places an undue burden on their
      female partners. In addition, excluding care for male infertility risks missing
      opportunities to diagnose important health conditions and identify reversible or
      irreversible causes of male infertility. Policymakers should consider providing
      equal coverage for male and female infertility care in future health insurance
      laws. 

PMID- 27030085
TI  - The effect of flutamide on the physical working capacity and activity of some of
      the key enzymes for the energy supply in adult rats.
AB  - The aim of the study was to assess the effects of androgen receptor antagonists
      on the physical working capacity and activity of some of the key muscle enzymes
      for the energy supply in rats. Young adult male Wistar rats were divided into two
      groups. One group received 15 mg kg-1 of flutamide daily for 6 days a week and
      the other group served as control for 8 weeks. At the beginning and at the end of
      the experiment, all rats were subjected to submaximal running endurance (SRE),
      maximum time to exhaustion (MTE), and maximal sprinting speed (MSS) tests. At the
      end of the trial, maximum oxygen consumption (VO2max) test was performed and the
      levels of testosterone, erythrocytes, hemoglobin as well as enzyme activity of
      succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), and NAD.H2-cytochrome
      c reductase (NAD.H2) of the gastrocnemius muscle were measured. Serum
      testosterone of the flutamide-treated rats was higher than that of the controls,
      which verifies the effectiveness of the dose chosen. MTE and SRE of the anti
      androgen-treated group were lower compared with the initial values. Flutamide
      treatment decreased the activity of SDH and NAD.H2 compared with the controls. We
      found no effect of the anti-androgen treatment on MSS, VO2max, running economy,
      LDH activity, and hematological variables. Our findings indicate that the
      maintenance of the submaximal and maximal running endurance as well as the
      activity of some of the key enzymes associated with muscle oxidative capacity is
      connected with androgen effects mediated by androgen receptors.

PMID- 27030087
TI  - Blooming rhythms of cactus Cereus peruvianus with nocturnal peak at full moon
      during seasons of prolonged daytime photoperiod.
AB  - Cereus peruvianus (Peruvian apple cactus) is a large erect and thorny succulent
      cactus characterized by column-like (cereus [L]: column), that is, candle-shaped,
      appendages. For three successive years (1100 days), between early April and late
      November, we studied the flowering patterns of eight cacti growing in public
      gardens and rural areas of north and central Tunisia, far from nighttime
      artificial illumination, in relation to natural environmental light, temperature,
      relative humidity and precipitation parameters. Flower blooming was assessed
      nightly between 23:00 h and until at least 02:00 h, and additionally around-the
      clock at ~1 h intervals for 30 consecutive days during the late summer of each
      year of study to quantify both nyctohemeral (day-night) and lunar patterns.
      During the summer months of prolonged daytime photoperiod, flower blooming of C.
      peruvianus exhibited predictable-in-time variation as "waves" with average period
      of 29.5 days synchronized by the light of the full moon. The large-sized flower
      (~16 cm diameter) opens almost exclusively at night, between sunset and sunrise,
      as a 24 h rhythm during a specific 3-4-day span of the lunar cycle (full moon),
      with a strong correlation between moon phase and number and proportion of flowers
      in bloom (ranging from r = +0.59 to +0.91). Black, blue and red cotton sheets
      were used to filter specific spectral bands of nighttime moonlight from
      illuminating randomly selected plant appendages as a means to test the hypothesis
      of a "gating" 24 h rhythm phenomenon of photoreceptors at the bud level. Relative
      to control conditions (no light filtering), black sheet covering inhibited flower
      bud induction by 87.5%, red sheet covering by 46.6% and blue sheet covering by
      34%, and the respective inhibiting effects on number of flowers in bloom were
      essentially 100%, ~81% and ~44%. C. peruvianus is a unique example of a
      terrestrial plant that exhibits a circadian flowering rhythm (peak ~00:00 h)
      "gated" by 24 h, lunar 29.5-day (bright light of full moon) and annual 365.25-day
      (prolonged summertime day length) environmental photoperiod cycles. 

PMID- 27030086
TI  - Varicocele management in the era of in vitro fertilization/intracytoplasmic sperm
      injection.
AB  - Varicocele is the most common surgically treatable cause of male infertility, and
      often results in alterations in semen parameters, sperm DNA damage, and changes
      to the seminal milieu. Varicocele repair can result in improvement in these
      parameters in the majority of men with clinical varicocele; data supporting
      repair in men with subclinical varicocele are less definitive. In couples seeking
      fertility using assisted reproductive technologies (ARTs), varicocele repair may
      offer improvement in semen parameters and sperm health that can increase the
      likelihood of successful fertilization using techniques such as in vitro
      fertilization (IVF) or intracytoplasmic sperm injection (ICSI), or may decrease
      the level of ART needed to achieve successful pregnancy. Male infertility is an
      indicator of general male health, and evaluation of the infertile male with an
      eye toward future health can facilitate optimal screening and treatment of these
      men. Furthermore, varicocele may represent a progressive lesion, offering an
      argument for its repair, although this is currently unclear. 

PMID- 27030088
TI  - Daily Administration of Short-Acting Liothyronine Is Associated with Significant
      Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.
AB  - BACKGROUND: Although most studies of levothyroxine-liothyronine combination
      therapy employ once-daily hormone administration, the kinetics of once-daily
      liothyronine have been studied infrequently. The aim of this study was to
      document both the peak and trough serum triiodothyronine (T3) levels that occur
      with once-daily liothyronine administration, along with changes in thyroid
      responsive parameters. METHODS: Participants with hypothyroidism were studied
      prospectively at an academic institution. Patients were switched from
      levothyroxine monotherapy to liothyronine monotherapy with 15 MUg liothyronine
      for two weeks, and then continued liothyronine at doses of 30-45 MUg for a
      further four weeks in an open-label, single-arm study. Weekly trough levels of T3
      were documented. In addition, hourly T3 concentrations immediately following
      liothyronine tablet administration were documented for eight hours during the
      sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4)
      concentrations were documented. Biochemical markers, markers of energy
      metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were
      also assessed. RESULTS: Mean serum TSH levels increased from 1.56 +/- 0.81 mIU/L
      at baseline to 5.90 +/- 5.74 mIU/L at two weeks and 3.84 +/- 3.66 mIU/L at six
      weeks. Trough T3 levels decreased from 99.5 +/- 22.9 to 91.9 +/- 40.2 at two
      weeks and recovered to 96.1 +/- 32.2 at six weeks. The peak T3 concentration
      after dosing of liothyronine during week 6 was 292.8 +/- 152.3 ng/dL. fT4 levels
      fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4.
      The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p =
      0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at
      weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine
      therapy increased from 6% to 39% over the study period. CONCLUSIONS: Once-daily
      dosing of liothyronine at doses of 30-45 MUg did not return serum TSH to the
      values seen during levothyroxine therapy. There were significant excursions in
      serum total and free T3 concentrations with once-daily therapy. Trials of
      combination therapy are likely to be associated with similar excursions, albeit
      of a lesser magnitude. Only the physical component score of the SF36
      questionnaire and hyperthyroid symptoms changed significantly with conversion to
      liothyronine monotherapy. Sustained release preparations with stable serum T3
      profiles may have entirely different outcomes.

PMID- 27030089
TI  - [The morphological changes in the myocardial tissue after sudden cardiac death
      from alcoholic cardiomyopathy].
AB  - This paper was designed to report the results of the retrospective analysis of
      the protocols of 180 forensic medical autopsy sections stored in the archives of
      Sankt-Petersburg Bureau of Forensic Medical Expertise and the data of the
      histological studies of myocardial tissues obtained after sudden cardiac death
      from alcoholic cardiomyopathy. The study revealed the following most
      pathognomonic histological criteria for alcoholic heart lesions: the alternation
      of hypertrophic and atrophic cardiomyocytes in the state of severe parenchymatous
      degeneration, pronounced mesenchymal fatty dystrophy in combination with
      pathological changes of the vascular walls (vascular wall plasmatization), sub
      endothelial accumulation of the PAS-positive tissue compounds, microcirculatory
      disorders in the form of erythrocyte stasis with the manifestations of the blood
      "sludge" phenomenon, and precapillary fibrosis. The signs of severe
      parenchymatous and stromal vascular dystrophy of the myocardial histohematic
      barrier (HHB) are supposed to reflect the toxic effects of ethanol and its
      metabolites that are directly involved in the mechanisms underlying the
      disturbances of intracellular metabolism and dyscirculatory events leading to the
      development of heart muscle hypoxia. 

PMID- 27030090
TI  - [The peculiarities of the evaluation of the severity of the harm to health in the
      case of development of psychic problems associated with the concomitant HIV
      infection and the accompanying infectious pathology].
AB  - The objective of the present study was to elaborate the qualifying criteria for
      the evaluation of the severity of the harm to health in the case of development
      of a psychic disease associated with the concomitant HIV infection and the
      accompanying infectious pathology, in the first place tuberculosis, venereal
      diseases, parenteral hepatitis B and C. The scientifically substantiated
      qualifying criteria are proposed to be used for the expert assessment of the harm
      to health in the case of development a psychic disease associated with the
      concomitant HIV infection and the accompanying infectious pathology. 

PMID- 27030091
TI  - [Characteristic of the fractures of the cervical, thoracic and lumbar vertebrae
      in the victims of a traffic accident found in the passenger compartment of a
      modern motor vehicle].
AB  - The objective of the present work was to study peculiar features of the injuries
      to three spinal regions in the victims of a head-on car collision found in the
      passenger compartments of modern motor vehicles equipped with seat belts and
      other safety means. It was shown that most frequent fatal injuries to the driver
      include the fractures of the cervical, thoracic, and lumbar vertebrae. These
      injuries are much less frequent in the passengers occupying the front and the
      right back seats. The multilayer and multiple character of the fractures in
      different parts of the spinal column in the car drivers is attributable to more
      pronounced spine flexion and extension associated with injuries of this kind. The
      fractures of the lower cervical vertebrae in the front seat passengers occur more
      frequently than injuries of a different type whereas the passengers of the back
      seats most frequently experience fractures of the upper cervical vertebrae. The
      passengers of the left back seat less frequently suffer from injuries to the
      thoracic spine than from the fractures of the cervical and lumbar vertebrae. The
      passengers of the central back seat most frequently experience fractures of the
      thoracic part of the vertebral column and the passengers occupying the right back
      seat fractures of the lumbar vertebrae. 

PMID- 27030092
TI  - [The characteristic of the construction features of the power saw blades from the
      results of experimental studies of power saw injuries to the long tubular bones].
AB  - The objective of the present study was to elucidate the characteristic
      morphological signs of the power saw injuries to human long tubular bones and
      thereby make possible distinguishing between those inflicted by different types
      of power jigsaws. The experiments were carried out with the use of the power saws
      with high-speed reciprocating motion of the blade (power jigsaws and sabre saws).
      The study was focused on the experimental saw injuries to the human long tubular
      bones inflicted by the power jigsaws and sabre saws. The mathematical analysis
      has demonstrated the possibility of determining the properties of the saws and
      blades employed to inflict the injury based on the morphological and dimensional
      changes in the long tubular bones. The results of the study indicate that the
      forensic medical expertise of the injuries inflicted by power saws with high
      speed reciprocating motion of the blade based on the morphological and
      dimensional changes in the long tubular bones makes it possible to identify with
      a probability of 98.6-99.7% both the construction and the size of the instrument
      used for sawing. 

PMID- 27030094
TI  - [Forensic medical diagnostics of intoxication with certain poisonous mushrooms in
      the case of the lethal outcome in a hospital].
AB  - The present study was undertaken with a view to improving forensic medical
      diagnostics of intoxication with poisonous mushrooms in the cases of patients'
      death in a hospital. A total of 15 protocols of forensic medical examination of
      the corpses of the people who had died from acute poisoning were available for
      the analysis. The deathly toxins were amanitin and muscarine contained in various
      combinations in the death cap (Amanita phalloides) and the early false morels
      (Gyromitra esculenta and G. gigas). The main poisoning season in the former case
      was May and in the latter case August and September (93.4%). The mortality rate
      in the case of group intoxication (such cases accounted for 40% of the total)
      amounted to 28.6%. 40% of the deceased subjects consumed mushrooms together with
      alcohol. The poisoning caused the development of either phalloidin- or gyromitrin
      intoxication syndromes (after consumption of Amanita phalloides and Gyromitra
      esculenta respectively). It is emphasized that the forensic medical experts must
      substantiate the diagnosis of poisoning with mushroom toxins based on the results
      of the chemical-toxicological and/or forensic chemical investigations. The
      relevant materials taken from the victim or the corpse should be dispatched for
      analysis not only within the first day but also on days 2-4 after intoxication.
      The mycological and genetic analysis must include the detection and
      identification of mushroom microparticles and spores in the smears from the oral
      cavity, vomiting matter, wash water, gastric and intestinal contents. In
      addition, the macro- and microscopic morphological signs, clinical data (major
      syndromes, results of laboratory studies, methods of treatment) should be taken
      into consideration as well as the time (season) of mushroom gathering,
      simultaneous poisoning in a group of people, and other pertinent information. 

PMID- 27030095
TI  - [The specific features of the distribution of 2,6-di-tret-buthyl-4
      methlhydroxybenzole in the organism of the warm-blooded animals].
AB  - We have studied the specific features of the distribution of 2,6-di-tret-buthyl-4
      methlhydroxybenzole in the organism of the omnivorous warm-blooded animals (rats)
      following the intragastric administration of the three-fold lethal dose of the
      poisonous substance. 2,6-di-tret-buthyl-4-methlhydroxybenzole was isolated from
      the blood and various organs of the animals by means of acetone extraction. It
      was further purified on the 40/100 mcm L silicagel column with the use of
      hexane/acetone for elution. TLC, GC-MS, and UV-spectrophotometry were employed to
      identify and quantify the material of interest. It was shown that 2,6-di-tret
      buthyl-4-methlhydroxybenzole undergoes modification in the internal organs and
      blood of the poisoned animals. In was present in the highest amounts (100 mg/g)
      in the stomach and small intestine contents (787.78+/-52.31 and 18.31+/-3.47
      respectively), spleen (12.46+/-1.02), and kidneys (8.48+/-0.61). 

PMID- 27030097
TI  - [The application of dermatoglyphics as a method for the characteristic of the
      personality traits for the purpose of the forensic medical identification
      expertise].
AB  - The authors report a case of forensic medical expertise demonstrating the
      potential of the dermatoglyphic technique as a tool for the identification of the
      personality traits of unknown individuals including their race and ethnic
      background, biological age, constitutional characteristics, congenital and
      acquired pathologies and injuries. It was shown that the results of the
      dermatoglyphic studies agree with and complement the data obtained with the help
      of a set of traditional forensic medical investigations, such as urological,
      odontoscopic, and roentgenological ones. An important advantage of the
      dermatoglyphic techniques is the possibility of their application under
      conditions when the choice and the use of the alternative methods are limited by
      the specific features of the objects of forensic medical expertise and the lack
      of time. 

PMID- 27030096
TI  - [The chemical toxicological analysis of sertindole].
AB  - Sertindole is an "non-typical" neuroleptic extensively used for the treatment of
      schizophrenic patients. The detection of intoxication with this medication
      implies the necessity of development of the optimal methods for its isolation
      from the biological materials and further identification. The objective of the
      present work was to study the influence of various factors on the efficiency of
      sertindole extraction from solutions, the elaboration of the methods for its
      isolation from biological objects, detection, and quantitative determination in
      the extracts from these objects. Investigations into the influence of various
      factors on the isolation of sertindole from solutions included characteristic of
      the chemical nature of the organic solvent and the electrolyte, measurements of
      pH, time and frequency of extraction with the use of UV spectrophotometry.
      Isolation of sertindole from the liver, kidneys, brain, heart, gastric and
      intestinal contents was carried out by the method of A.A. Vasil'ev. Moreover, we
      have developed an original method for the detection of sertindole in the extracts
      using TLC, UV spectrophotometry, and HPLC. The qualitative determination of
      sertindole in the extracts from the internal organs, blood plasma, and urine was
      performed by HPLC. The optimal conditions for sertindole liberation from the
      extracts have been found and TLC-screening conditions proposed. The TLC, UV
      spectrophotometric, and HPLC techniques specially modified for the determination
      of sertindole in the extracts were used. It was shown that the maximum amounts of
      sertindole were present in the liver and brain within 24 hours after acute
      poisoning. In the kidneys, stomach, and intestines, it accumulated in smaller
      quantities Extracts from the heart did not contain sertindole. Maximum efficiency
      of the sertindole extraction during 24 hours was achived from blood plasma. 

PMID- 27030098
TI  - [The reliable and plausible conclusions in the decisions of the forensic medical
      experts].
AB  - The authors characterize in brief the conclusions drawn by the forensic medical
      experts in the course of their professional activities with special reference to
      their reliability and plausibility. The most common errors creeping into the
      conclusions are discussed together with the approaches to their prevention and/or
      correction. This article continues a series of publications of the same authors
      concerning the main logical errors encountered in the conclusions of the forensic
      medical experts. The results of a deeper analysis of such errors will be
      published elsewhere.

PMID- 27030099
TI  - Prevention of hormonal breast cancer by dietary jamun.
AB  - SCOPE: Syzygium cumini (jamun) is perhaps the only berry that has the diversity
      of anthocyanidins of blueberry and bilberry and the abundance of
      ellagitannins/ellagic acid of black raspberry. Here, we report the potential of
      jamun against 17beta-estrogen-mediated breast cancer and the role of miRNAs and
      other targets in disease inhibition. METHODS AND RESULTS: Female August
      Copenhagen Irish rats were given AIN-93M diet or diet supplemented with jamun.
      Two weeks later, animals received 17beta-estradiol and were palpated weekly for
      the mammary tumors. At the end of 26 weeks, the jamun-diet significantly delayed
      the first tumor appearance by 21 days, and reduced the tumor incidence (65%
      versus 96%), tumor burden (313 +/- 95 versus 661 +/- 123 mm(3) ) and tumor
      multiplicity (1.8 +/- 0.3 versus 4.2 +/- 0.4 tumors/rat) compared to control. The
      experimental diet significantly reduced the estrogen-associated growth of
      pituitary prolactinomas, circulating prolactin and estradiol levels and offset
      estrogen-associated increases in mammary cell-proliferation, estrogen receptor
      alpha (ER-alpha), and cyclinD1. miRNAs that were either overexpressed (miR-182
      and miR-375) or underexpressed (miR-127 and miR-206) following estrogen-treatment
      were significantly protected by jamun diet. CONCLUSIONS: Together, our data show
      that jamun significantly offset estrogen-mediated alterations in mammary cell
      proliferation, ER-alpha, cyclinD1, and candidate miRNAs, and that the modulation
      of these biomarkers correlated with a reduction in mammary carcinogenicity.

PMID- 27030101
TI  - Influence of meteorological data on sun tolerance in patients with erythropoietic
      protoporphyria in France.
AB  - BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare metabolic disorder,
      characterized by photosensitivity, caused by errors of the haem biosynthetic
      pathway. Avoidance of sun exposure is recommended; however, some patients
      suggested a paradoxical improvement of symptoms when they move to sunny areas.
      OBJECTIVES: In a national French study, we sought to investigate the influence of
      sun exposure on EPP symptoms. MATERIALS AND METHODS: We used a national
      transversal observational study by questionnaire. Patients were selected from the
      national record of the Centre Francais des Porphyries (French Porphyrias referral
      centre). Sun exposure level by geographic area was assessed using climate data
      provided by the French national meteorological service (Meteo France). RESULTS:
      Eighty-nine patients were included. We notably observed that 40% of patients
      declared an improvement in their tolerance of sun exposure after repeated sun
      exposures. In the more sunny areas, the intensity of the pain was lower (r = 
      0.26) and the duration of the sun exposure responsible for flares was longer (r =
      0.39) than in the areas that were less sunny (P < 0.05). CONCLUSIONS: This study
      proposes a benefit of natural progressive sun exposure for patients with EPP.

PMID- 27030100
TI  - Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced
      Smad1/5/8 phosphorylation.
AB  - Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone
      and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in
      cartilage and regulates chondrogenesis, and mutations have been shown to cause
      osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue;
      however, its role during tooth development is unclear. Here, we used cell culture
      and in vivo analyses to determine the role of GDF5 during tooth development. GDF5
      and its associated BMP receptors are expressed at the protein and mRNA levels
      during postnatal tooth development, particularly at a stage associated with
      enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the
      differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this
      differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed
      enhanced enamel formation in both the incisors and molars, but not in the tooth
      roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2
      mediated mRNA expression of enamel matrix proteins and downstream phosphorylation
      of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast
      differentiation via accelerated BMP2-signalling. 

PMID- 27030102
TI  - Systematic quantification of HDR and NHEJ reveals effects of locus, nuclease, and
      cell type on genome-editing.
AB  - Precise genome-editing relies on the repair of sequence-specific nuclease-induced
      DNA nicking or double-strand breaks (DSBs) by homology-directed repair (HDR).
      However, nonhomologous end-joining (NHEJ), an error-prone repair, acts
      concurrently, reducing the rate of high-fidelity edits. The identification of
      genome-editing conditions that favor HDR over NHEJ has been hindered by the lack
      of a simple method to measure HDR and NHEJ directly and simultaneously at
      endogenous loci. To overcome this challenge, we developed a novel, rapid, digital
      PCR-based assay that can simultaneously detect one HDR or NHEJ event out of 1,000
      copies of the genome. Using this assay, we systematically monitored genome
      editing outcomes of CRISPR-associated protein 9 (Cas9), Cas9 nickases,
      catalytically dead Cas9 fused to FokI, and transcription activator-like effector
      nuclease at three disease-associated endogenous gene loci in HEK293T cells, HeLa
      cells, and human induced pluripotent stem cells. Although it is widely thought
      that NHEJ generally occurs more often than HDR, we found that more HDR than NHEJ
      was induced under multiple conditions. Surprisingly, the HDR/NHEJ ratios were
      highly dependent on gene locus, nuclease platform, and cell type. The new assay
      system, and our findings based on it, will enable mechanistic studies of genome
      editing and help improve genome-editing technology. 

PMID- 27030103
TI  - Classification of Vitreous Seeds in Retinoblastoma: Correlations with Patient,
      Tumor, and Treatment Characteristics.
AB  - PURPOSE: To evaluate the patient, disease, and tumor characteristics of the 3
      morphologically distinct groups of vitreous seeds in retinoblastoma presenting
      for treatment with ophthalmic artery chemosurgery (OAC): dust (class 1), spheres
      (class 2), and clouds (class 3) in primary and recurrent vitreous seeds. DESIGN:
      Retrospective cohort study of patients treated for vitreous seeds at Memorial
      Sloan Kettering Cancer Center between May 2006 and March 2015. PARTICIPANTS: A
      total of 135 eyes with active vitreous seeds, presenting for primary treatment
      with OAC or with recurrent vitreous disease. METHODS: Vitreous seeds were
      classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy,
      fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to
      locate and evaluate the extent of retinal and vitreous disease. Patient and
      disease characteristics (age, laterality of disease, treatment status) were
      compared among classification groups. A 2-tailed Fisher exact test and paired
      Student t test were used for statistical analysis. MAIN OUTCOME MEASURES: Age of
      patient, laterality of disease, location of retinal disease, extent of vitreous
      disease, and treatment status. RESULTS: Primary treated disease: Patients with
      eyes containing class 3 (cloud) vitreous seeds were significantly older than
      patients with class 1 or 2 seeds (P < 0.05). The median age of patients with
      class 1, 2, and 3 seeds was 11, 15.5, and 32 months, respectively. Eyes
      containing class 3 seeds were significantly more likely to occur in the equator
      ora region of the fundus (P < 0.0001), in a diffuse pattern (P < 0.0001), and in
      patients with unilateral disease (P < 0.05), compared with class 1 and 2 seeds.
      Recurrent disease: Recurrent vitreous seeds were significantly more common to
      class 2 (P < 0.05), occurring in a diffuse pattern (P = 0.01) and in patients
      with bilateral disease (P < 0.001). CONCLUSIONS: The 3 classes of vitreous seeds
      have distinct clinical characteristics associated with the age of patient,
      laterality of disease, and extent and location of tumor-producing seeds.
      Furthermore, recurrent vitreous seeds appear to have a unique clinical profile
      compared with seeds receiving primary treatment.

PMID- 27030104
TI  - Topical 5-Fluorouracil 1% as Primary Treatment for Ocular Surface Squamous
      Neoplasia.
AB  - PURPOSE: To determine the efficacy of topical 5-fluorouracil 1% (5-FU) as a
      primary treatment of ocular surface squamous neoplasia (OSSN). DESIGN:
      Retrospective study. PARTICIPANTS: Topical 5-FU was used as primary therapy in 44
      patients with OSSN. METHODS: 5-Fluorouracil 1% administered topically 4 times
      daily for 1 week followed by a drug holiday of 3 weeks. Patients were identified
      through a pharmacy database. Patients were excluded if 5-FU was used as adjuvant
      therapy, if they did not complete therapy, or if they were still actively
      receiving treatment for OSSN at the time of last follow-up. MAIN OUTCOME
      MEASURES: The primary outcome measures were the frequency of complete resolution
      with topical 5-FU treatment and the rate of OSSN recurrence. RESULTS: Of the 44
      patients identified, 32 were men and 12 were women. The mean age was 68 years.
      Complete resolution of OSSN was noted in 82% of patients (36/44); 18% (8/44) were
      considered treatment nonresponders. Patients were treated with a median of 4
      cycles (range, 2-9 cycles). Nasal location was the only risk factor identified
      for nonresponse to therapy (P = 0.04). The median follow-up after resolution was
      10 months (range, 2-77 months). In the 36 patients who showed complete
      resolution, 4 experienced tumor recurrence. Recurrence rates at 1 and 2 years
      were 6% and 15%, respectively, using Kaplan-Meier survival analysis. At least 1
      side effect from the medication was reported by 61% of patients (21/44), but only
      1 patient discontinued the medication because of intolerance. The most common
      side effect was pain (n = 17; 39%), followed by tearing (n = 10; 23%),
      photophobia (n = 6; 14%), itching (n = 4; 9%), swelling (n = 2; 5%), and
      infection (n = 1; 2%). No long-term complications were reported. CONCLUSIONS: 5
      Fluorouracil is effective and well tolerated as a primary treatment for OSSN,
      with 82% of tumors responding completely to therapy.

PMID- 27030105
TI  - Personal Health Record Use in the United States: Forecasting Future Adoption
      Levels.
AB  - BACKGROUND: Personal health records (PHRs) offer a tremendous opportunity to
      generate consumer support in pursing the triple aim of reducing costs, increasing
      access, and improving care quality. Moreover, surveys in the United States
      indicate that consumers want Web-based access to their medical records. However,
      concerns that consumers' low health information literacy levels and physicians'
      resistance to sharing notes will limit PHRs' utility to a relatively small
      portion of the population have reduced both the product innovation and policy
      imperatives. OBJECTIVE: The purpose of our study was 3-fold: first, to report on
      US consumers' current level of PHR activity; second, to describe the roles of
      imitation and innovation influence factors in determining PHR adoption rates; and
      third, to forecast future PHR diffusion uptake among US consumers under 3
      scenarios. METHODS: We used secondary data from the Health Information National
      Trends Survey (HINTS) of US citizens for the survey years 2008, 2011, and 2013.
      Applying technology diffusion theory and Bass modeling, we evaluated 3 future PHR
      adoption scenarios by varying the introduction dates. RESULTS: All models
      displayed the characteristic diffusion S-curve indicating that the PHR technology
      is likely to achieve significant market penetration ahead of meaningful use
      goals. The best-performing model indicates that PHR adoption will exceed 75% by
      2020. Therefore, the meaningful use program targets for PHR adoption are below
      the rates likely to occur without an intervention. CONCLUSIONS: The promise of
      improved care quality and cost savings through better consumer engagement
      prompted the US Institute of Medicine to call for universal PHR adoption in 1999.
      The PHR products available as of 2014 are likely to meet and exceed meaningful
      use stage 3 targets before 2020 without any incentive. Therefore, more ambitious
      uptake and functionality availability should be incorporated into future goals.

PMID- 27030106
TI  - Oxidation-reduction potential and lipid oxidation in ready-to-eat blue mussels in
      red sauce: criteria for package design.
AB  - BACKGROUND: Ready-to-eat in-package pasteurized blue mussels in red sauce
      requires refrigerated storage or in combination with an aerobic environment to
      prevent the growth of anaerobes. A low barrier packaging may create an aerobic
      environment; however, it causes lipid oxidation in mussels. Thus, evaluation of
      the oxidation-reduction potential (Eh) (aerobic/anaerobic nature of food) and
      lipid oxidation is essential. Three packaging materials with oxygen transmission
      rate (OTR) of 62 (F-62), 40 (F-40) and 3 (F-3) cm3 m-2 day-1 were selected for
      this study. Lipid oxidation was measured by color changes in thiobarbituric acid
      reactive substances (TBARS) at 532 nm (TBARS@532) and 450 nm (TBARS@450).
      RESULTS: Significantly higher (P < 0.05) TBARS@532 was found in mussels packaged
      in higher OTR film. TBARS@450 in mussels packaged with F-62 and F-40 gradually
      increased during refrigerated storage (3.5 +/- 0.5  degrees C), but remained
      constant after 20 days of storage for mussels packaged with F-3. The Eh of
      pasteurized sauce was not significantly affected (P > 0.05) by OTR and remained
      negative (< -80 mV) during storage. Negative Eh values can support the growth of
      anaerobes such as Clostridium botulinum. The headspace oxygen concentration was
      reduced by about 50% from its initial value during pasteurization, and then
      further declined during storage. The headspace oxygen concentration was higher in
      trays packaged with higher OTR film. CONCLUSION: Mussels packed with high OTR
      film showed higher lipid oxidation, indicating that high barrier film is required
      for packaging of mussels. Pasteurized mussels must be kept in refrigerated
      storage to prevent growth of anaerobic proteolytic C. botulinum spores under
      temperature abuse. (c) 2016 Society of Chemical Industry.

PMID- 27030107
TI  - A (1)H HR-MAS NMR-Based Metabolomic Study for Metabolic Characterization of Rice
      Grain from Various Oryza sativa L. Cultivars.
AB  - Rice grain metabolites are important for better understanding of the plant
      physiology of various rice cultivars and thus for developing rice cultivars aimed
      at providing diverse processed products. However, the variation of global
      metabolites in rice grains has rarely been explored. Here, we report the
      identification of intra- or intercellular metabolites in rice (Oryza sativa L.)
      grain powder using a (1)H high-resolution magic angle spinning (HR-MAS) NMR-based
      metabolomic approach. Compared with nonwaxy rice cultivars, marked accumulation
      of lipid metabolites such as fatty acids, phospholipids, and
      glycerophosphocholine in the grains of waxy rice cultivars demonstrated the
      distinct metabolic regulation and adaptation of each cultivar for effective
      growth during future germination, which may be reflected by high levels of
      glutamate, aspartate, asparagine, alanine, and sucrose. Therefore, this study
      provides important insights into the metabolic variations of diverse rice
      cultivars and their associations with environmental conditions and genetic
      backgrounds, with the aim of facilitating efficient development and the
      improvement of rice grain quality through inbreeding with genetic or chemical
      modification and mutation. 

PMID- 27030109
TI  - R26-WntVis reporter mice showing graded response to Wnt signal levels.
AB  - The canonical Wnt signaling pathway plays a major role in the regulation of
      embryogenesis and organogenesis, where signal strength-dependent cellular
      responses are of particular importance. To assess Wnt signal levels in individual
      cells, and to circumvent the integration site-dependent bias shown in previous
      Wnt reporter lines, we constructed a new Wnt signal reporter mouse line R26
      WntVis. Heptameric TCF/LEF1 binding sequences were combined with a viral minimal
      promoter to confer a graded response to the reporter depending on Wnt signal
      strengths. The histone H2B-EGFP fusion protein was chosen as the fluorescent
      reporter to facilitate single-cell resolution analyses. This WntVis reporter gene
      was then inserted into the ROSA26 locus in an orientation opposite to that of the
      endogenous gene. The R26-WntVis allele was introduced into Wnt3a(-/-) and
      Wnt3a(vt/-) mutant mouse embryos and compared with wild-type embryos to assess
      its performance. The R26-WntVis reporter was activated in known Wnt-dependent
      tissues and responded in a graded fashion to signal intensity. This analysis also
      indicated that the major Wnt activity early in embryogenesis switched from Wnt3
      to Wnt3a around E7.5. The R26-WntVis mouse line will be widely useful for the
      study of Wnt signal-dependent processes. 

PMID- 27030108
TI  - Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and
      genome stability.
AB  - Temporal regulation of microtubule dynamics is essential for proper progression
      of mitosis and control of microtubule plus-end tracking proteins by
      phosphorylation is an essential component of this regulation. Here we show that
      Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at
      multiple sites within the amino terminus and a cluster of serine/threonine
      residues in the linker connecting the calponin homology and end-binding homology
      domains. EB2 phosphorylation, which is strictly associated with mitotic entry and
      progression, reduces the binding affinity of EB2 for microtubules. Expression of
      non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and
      delays formation of bipolar metaphase plates in a microtubule binding-dependent
      manner, and leads to aneuploidy even in unperturbed mitosis. We propose that
      Aurora B and CDK1 temporally regulate the binding affinity of EB2 for
      microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic
      progression and genome stability. 

PMID- 27030111
TI  - David Southall: Determined, honest, and anxious.

PMID- 27030112
TI  - Armed Conflict in the Federally Administered Tribal Areas of Pakistan and the
      Role of NGOs in Restoring Health Services.
AB  - The Federally Administered Tribal Areas (FATA) of Pakistan have been a hotbed of
      terrorists' violence since 9/11. The unremitted armed conflict in the region and
      limited role of the government in delivering fundamental health services has left
      the people at the disposal of nongovernmental organizations (NGOs). This research
      aims at empirically substantiating the successful strategies adopted by the NGOs
      to run their projects under threats and to know the perceptions of the community
      toward NGOs and their services. Triangulation methodology was adopted in
      collecting data. Based on results, the research found that health care is a
      highly demanded service in the study area, and the government does not have the
      capacity nor the resources to ensure decent health coverage for all the people of
      the region. NGOs indeed have a crucial role not only in building the capacity of
      the government and the community but also in restoring and providing health
      services in the region, but still many efforts are required to overcome the
      challenges they are facing. By implication, the research places forward some
      recommendations.

PMID- 27030110
TI  - Insights into the C-terminal Peptide Binding Specificity of the PDZ Domain of
      Neuronal Nitric-oxide Synthase: CHARACTERIZATION OF THE INTERACTION WITH THE
      TIGHT JUNCTION PROTEIN CLAUDIN-3.
AB  - Neuronal nitric-oxide synthase, unlike its endothelial and inducible
      counterparts, displays a PDZ (PSD-95/Dlg/ZO-1) domain located at its N terminus
      involved in subcellular targeting. The C termini of various cellular proteins
      insert within the binding groove of this PDZ domain and determine the subcellular
      distribution of neuronal NOS (nNOS). The molecular mechanisms underlying these
      interactions are poorly understood because the PDZ domain of nNOS can apparently
      exhibit class I, class II, and class III binding specificity. In addition, it has
      been recently suggested that the PDZ domain of nNOS binds with very low affinity
      to the C termini of target proteins, and a necessary simultaneous lateral
      interaction must take place for binding to occur. We describe herein that the PDZ
      domain of nNOS can behave as a bona fide class III PDZ domain and bind to C
      terminal sequences with acidic residues at the P-2 position with low micromolar
      binding constants. Binding to C-terminal sequences with a hydrophobic residue at
      the P-2 position plus an acidic residue at the P-3 position (class II) can also
      occur, although interactions involving residues extending up to the P-7 position
      mediate this type of binding. This promiscuous behavior also extends to its
      association to class I sequences, which must display a Glu residue at P-3 and a
      Thr residue at P-2 By means of site-directed mutagenesis and NMR spectroscopy, we
      have been able to identify the residues involved in each specific type of binding
      and rationalize the mechanisms used to recognize binding partners. Finally, we
      have analyzed the high affinity association of the PDZ domain of nNOS to claudin
      3 and claudin-14, two tight junction tetraspan membrane proteins that are
      essential components of the paracellular barrier.

PMID- 27030113
TI  - A Kv7.2 mutation associated with early onset epileptic encephalopathy with
      suppression-burst enhances Kv7/M channel activity.
AB  - Mutations in the KCNQ2 gene encoding the voltage-gated potassium channel subunit
      Kv7.2 cause early onset epileptic encephalopathy (EOEE). Most mutations have been
      shown to induce a loss of function or to affect the subcellular distribution of
      Kv7 channels in neurons. Herein, we investigated functional consequences and
      subcellular distribution of the p.V175L mutation of Kv7.2 (Kv7.2(V175L) ) found
      in a patient presenting EOEE. We observed that the mutation produced a 25-40 mV
      hyperpolarizing shift of the conductance-voltage relationship of both the
      homomeric Kv7.2(V175L) and heteromeric Kv7.2(V175L) /Kv7.3 channels compared to
      wild-type channels and a 10 mV hyperpolarizing shift of Kv7.2(V175L) /Kv7.2/Kv7.3
      channels in a 1:1:2 ratio mimicking the patient situation. Mutant channels also
      displayed faster activation kinetics and an increased current density that was
      prevented by 1 MUm linopirdine. The p.V175L mutation did not affect the protein
      expression of Kv7 channels and its localization at the axon initial segment. We
      conclude that p.V175L is a gain of function mutation. This confirms previous
      observations showing that mutations having opposite consequences on M channels
      can produce EOEE. These findings alert us that drugs aiming to increase Kv7
      channel activity might have adverse effects in EOEE in the case of gain-of
      function variants.

PMID- 27030114
TI  - Association Between Periodontal Disease and Erectile Dysfunction: A Systematic
      Review.
AB  - A limited number of studies have reported an association between erectile
      dysfunction (ED) and chronic periodontitis (CP). The aim of the present study is
      to assess the association between CP and ED through a systematic review of
      published literature. To address the focused question, "Is there a relationship
      between ED and CP?" indexed databases were searched till December 2015 using
      various key words "erectile dysfunction," "periodontal disease," "periodontitis,"
      "dental infection," and "impotence." Letters to the editor, commentaries,
      historic reviews, and experimental studies were excluded. The pattern of the
      present systematic review was customized to primarily summarize the pertinent
      data. Nine studies were included. Seven studies had a cross-sectional design and
      two studies were randomized control trials. The number of study participants
      ranged between 53 and 513,258 individuals with age ranging between 20 years and
      85 years (median age ranging between 34.9 +/- 4.9 years and 50.9 +/- 16.6 years).
      In all studies, a positive relationship between CP and ED was reported. In four
      studies, odds ratio were reported, ranging between 1.53 and 3.35. From the
      literature reviewed, there seems to be a positive association between ED and CP;
      however, further well-designed controlled clinical trials are needed in this
      regard. It is emphasized that physicians should refer patients with ED to oral
      health care providers for a comprehensive oral evaluation and treatment.

PMID- 27030115
TI  - Toward Superconducting Critical Current by Design.
AB  - A new critical-current-by-design paradigm is presented. It aims at predicting the
      optimal defect landscape in superconductors for targeted applications by
      elucidating the vortex dynamics responsible for the bulk critical current. To
      this end, critical current measurements on commercial high-temperature
      superconductors are combined with large-scale time-dependent Ginzburg-Landau
      simulations of vortex dynamics. 

PMID- 27030116
TI  - Selective plane illumination microscopy on a chip.
AB  - Selective plane illumination microscopy can image biological samples at a high
      spatiotemporal resolution. Complex sample preparation and system alignment
      normally limit the throughput of the method. Using femtosecond laser
      micromachining, we created an integrated optofluidic device that allows obtaining
      continuous flow imaging, three-dimensional reconstruction and high-throughput
      analysis of large multicellular spheroids at a subcellular resolution.

PMID- 27030117
TI  - [Anti-diabetic therapy and cardiovascular disease].

PMID- 27030118
TI  - [Cardiovascular disease prevention in adults with type 2 diabetes mellitus
      according to the recent statement from the American Heart Association/American
      Diabetes Association].
AB  - There is a clear epidemiologic association between glycemic control and
      cardiovascular disease. There is strong evidence of a microvascular benefit by
      lowering glycated hemoglobin <7% while acknowledging lack of proven macrovascular
      benefits. It is therefore relevant, in all diabetic patients, to control all
      major cardiovascular risk factors such as obesity, hypertension, and
      dyslipidemia. These risk factors, easily measurable, account for 90% of acute
      myocardial infarction. In this review, the update on prevention of cardiovascular
      disease in adults with type 2 diabetes mellitus from the American Heart
      Association and the American Diabetes Association is discussed and commented. 

PMID- 27030119
TI  - [Incretin therapies and multifactorial clinical approach to cardiometabolic
      patients].
AB  - Atherogenic dyslipidemia, hypertension and obesity are frequently present in type
      2 diabetes mellitus (T2DM) and contribute to the overall increase in
      cardiovascular (CV) morbidity and mortality associated with this disease. It is
      therefore highly desirable that treatments aimed to improving glucose control in
      T2DM do not negatively impact such risk factors. It would be very helpful,
      instead, if treatments implemented to lower blood glucose could also be
      efficacious in mitigating hypertension, obesity and dyslipidemia, so to improve
      global CV risk profile in these patients. Glucagon-like peptide 1 receptor
      agonists (GLP-1RA) can efficiently ameliorate blood glucose profile in diabetic
      subjects with no or minimal risk of hypoglycemia: besides, the use of these
      agents is associated with weight loss, decreased blood pressure and a modestly
      but significantly improved lipid profile. Clinical trials and meta-analyses have
      also demonstrated that patients treated with exenatide and, to a larger extent,
      with liraglutide are significantly more likely to achieve the composite endpoint
      of glycated hemoglobin <7%, no hypoglycemia and no weight gain as compared to
      patients exposed to other diabetes treatment, including dipeptidyl peptidase-4
      inhibitors and insulin glargine. Thus, even if randomized controlled outcome
      trials definitely demonstrating a reduction in CV events in GLP-1RA treated
      subjects are still lacking, it is nevertheless evident that treatment with GLP
      1RA, by its action on CV risk factors, could contribute to mitigate the risk
      profile in T2DM. 

PMID- 27030120
TI  - [Cardiovascular effects of insulin therapy: from pharmacology to clinical
      trials].
AB  - Insulin has direct effects on vascular walls which, depending on experimental
      models, can be either predominantly antiatherogenic or proatherogenic. In
      observational studies, insulin therapy is usually associated with an increase in
      the incidence of major cardiovascular events. However, this result is probably
      determined by the effect of confounders. In clinical trials performed in the
      acute phase of coronary syndromes, the benefits observed with insulin therapy are
      probably due to the improvement of glycemic control, rather than to direct
      effects of insulin on the cardiovascular system. In long-term trials for primary
      or secondary prevention such as UKPDS and ORIGIN insulin has no relevant effects
      on major cardiovascular events beyond those determined by the improvement of
      metabolic control. On the other hand, severe hypoglycemia, which is a possible
      side effect of insulin therapy, is associated with a worse prognosis of
      cardiovascular disease. The availability of new long-acting insulin analogs,
      which reduce the incidence of hypoglycemia for similar levels of glycemic
      control, makes insulin therapy easier and potentially safer for the
      cardiovascular system. 

PMID- 27030121
TI  - [Cardiovascular outcome clinical trials in type 2 diabetes mellitus: what are the
      epidemiological and methodological evidence and the first evaluations to date?].
AB  - Clinical trials of glucose-lowering strategies in patients with type 2 diabetes
      mellitus (T2DM) have shown a favorable effect of intensive glycemic control on
      microvascular complications but failed to show a clear benefit on cardiovascular
      events. In 2008, the US Food and Drug Administration (FDA) and European Medicines
      Agency (EMA) have required stringent criteria to approve new glucose-lowering
      drugs, demanding proof of cardiovascular safety. As a result of these regulatory
      requirements, a number of cardiovascular outcome trials in T2DM have been
      conducted examining the cardiovascular safety of novel glucose-lowering drugs.
      Dipeptidyl peptidase 4 (DPP4) inhibitors, analogs of glucagon-like peptide 1 (GLP
      1), and inhibitors of the renal sodium-glucose linked transporter-2 (SGLT2) are
      new classes of glucose-lowering drugs for subjects with T2DM. The results of the
      cardiovascular outcome trials comparing the DPP4 inhibitors saxagliptin,
      alogliptin, and sitagliptin or the GLP-1 analog lixisenatide to placebo have
      demonstrated that these drugs are safe. The results of a cardiovascular outcome
      trial comparing the SGLT2 inhibitor empagliflozin to placebo have been published.
      Notably, empagliflozin treatment has been associated with a significant reduction
      in the primary composite cardiovascular outcome. Although the question regarding
      the positive effect of glycemic control on cardiovascular risk is still
      unanswered, current evidence suggests that a multifactorial approach aimed at
      treating not only hyperglycemia but also classical cardiovascular risk factors is
      necessary in order to reduce the risk of cardiovascular events in patients with
      T2DM. 

PMID- 27030123
TI  - Hispanic Nurses' Knowledge of and Approach to Pain Assessment and Management.
AB  - PURPOSE: This study sought to determine whether (a) Hispanic nurses differ in
      assessment and management of pain for Hispanic versus non-Hispanic patients and
      (b) relationships exist between measures of acculturation and Hispanic nurses'
      assessment and pain management. METHOD: A descriptive, cross-sectional
      correlation design study used three survey instruments to identify Hispanic
      nurses' cultural beliefs and how they approach pain management in clinical
      settings. RESULTS: The average nurse had inadequate knowledge. However, a sample
      strength was accurate pain assessment for both non-Hispanic and Hispanic
      patients; they had higher pain management decision-making scores for Hispanic
      patients. CONCLUSION: Results are consistent with empirical findings that nurses
      in general have inadequate knowledge of pain management, with important
      implications regarding needing further research and training in this area.
      IMPLICATIONS FOR PRACTICE: Future research should examine whether other ethnic
      groups are more likely to make correct decisions in pain management for members
      of their ethnic group.

PMID- 27030122
TI  - Extracellular ATP protects endothelial cells against DNA damage.
AB  - Cell damage can lead to rapid release of ATP to extracellular space resulting in
      dramatic change in local ATP concentration. Evolutionary, this has been
      considered as a danger signal leading to adaptive responses in adjacent cells.
      Our aim was to demonstrate that elevated extracellular ATP or inhibition of
      ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39) activity could be
      used to increase tolerance against DNA-damaging conditions. Human endothelial
      cells, with increased extracellular ATP concentration in cell proximity, were
      more resistant to irradiation or chemically induced DNA damage evaluated with the
      DNA damage markers gammaH2AX and phosphorylated p53. In our rat models of DNA
      damage, inhibiting CD39-driven ATP hydrolysis with POM-1 protected the heart and
      lung tissues against chemically induced DNA damage. Interestingly, the phenomenon
      could not be replicated in cancer cells. Our results show that transient increase
      in extracellular ATP can promote resistance to DNA damage.

PMID- 27030124
TI  - Cerebral malaria is associated with long-term mental health disorders: a cross
      sectional survey of a long-term cohort.
AB  - BACKGROUND: Cerebral malaria (CM) and severe malarial anaemia (SMA) are
      associated with neuro-developmental impairment in African children, but long-term
      mental health disorders in these children are not well defined. METHODS: A cohort
      of children previously exposed to CM (n = 173) or SMA (n = 99) had neurologic
      assessments performed and screening for behaviour difficulties using the
      Strengths and Difficulties Questionnaire (SDQ) a median of 21 months after the
      disease episode. These findings were compared to concurrently recruited community
      children (CC, n = 108). Participants with SDQ total difficulties score >= 17 had
      a mental health interview with the child and adolescent version of the Mini
      International Neuropsychiatric Interview (MINI-KID) and a sample had brain
      magnetic resonance imaging (MRI). RESULTS: Fifty-five children had SDQ score >=
      17. On the MINI-KID, these children were classified as having no difficulties (n
      = 18), behaviour difficulties only (n = 13) or a mental health disorder (n = 24).
      Behaviour difficulties were seen in similar frequencies in CM (3.5%), SMA (4.0%)
      and CC (2.8%). In contrast, mental health disorders were most frequent in CM
      (10.4%), followed by SMA (4.0%) and CC (1.8%). Externalizing disorders (conduct,
      oppositional defiance and attention deficit hyperactivity) were the most common
      mental health disorders. The median total coma duration was 72 (IQR 36.0-115.0) h
      in patients with mental health disorders compared to 48 (IQR 28.5-78.7) h in
      those without, p = 0.039. Independent risk factors for mental health disorder
      included neurologic deficit at discharge (OR 4.09 (95% CI 1.60, 10.5) and seizure
      recurrences during hospitalization, (OR 2.80, 95% CI 1.13, 6.97). Brain MRI
      findings consistent with small vessel ischaemic neural injury was seen in over
      half of these children. CONCLUSIONS: Cerebral malaria may predispose children to
      mental health disorders, possibly as a consequence of ischaemic neural injury.
      There is urgent need for programmes of follow-up, diagnosis and interventions for
      these children.

PMID- 27030125
TI  - Ecotoxicological evaluation of foundry sands and cosmetic sludges using new
      earthworm biomarkers.
AB  - The management and final disposal of industrial wastes are a matter of
      considerable human concern. The present study evaluates the cyto/genotoxic
      effects and changes of the coelomic cell formulas exerted by aqueous leachates
      and solid waste (SW) of two industrial residues using coelomocytes extruded from
      Eisenia fetida. The assayed wastes corresponded to industrial foundry and
      cosmetic activities. After 14 days of exposure, we obtained a group of endpoints
      that reflect the toxicity/genotoxicity, coelomocyte formula and indexes; and the
      mortality classical value (LC50-14d). Among the variables measured, total
      coelomocytes formula (eleocytes + amebocytes + granulocytes) appears as a single
      and easy parameter to assess the toxicity of eluates at short exposure times. We
      applied a set of assays using earthworms as test organism that would allow
      evaluating SW as well as its aqueous leachates. It is easy to run trials
      combining exposures of 1 h to 14 days, which can be integrated into the
      implementation of the traditional test for evaluating acute toxicity. 

PMID- 27030126
TI  - Primary ectopic substernal thyroid cancer with trachea relapse: a case report and
      opinions of management.
AB  - BACKGROUND: Ectopic substernal thyroid is a rare symptom of thyroid disease that
      entirely results from the developmental defects at early stages of thyroid
      embryogenesis and during its descent. Cases were seldom reported as primary
      ectopic substernal thyroid cancer, especially those with severe local invasion
      and tracheal relapse. CASE PRESENTATION: In this report, the patient presented
      odynophagia and a sense of progressing swallowing obstruction. She underwent
      total thyroidectomy and lump resection. However, she refused to use postoperative
      radioactive iodine or take adjuvant external-beam radiotherapy, except for
      thyroid hormone replacement therapy. Tracheal relapse was observed after 6
      months. Tracheal stent was used to reconstruct the airway twice. CONCLUSIONS:
      Trachea invasion might be a worse independent predictor of prognosis than any
      others and should be given particular attention. Furthermore, tracheal stent
      might be a palliative option for patients with tracheal relapse.

PMID- 27030127
TI  - Neural adaptations to submaximal isokinetic eccentric strength training.
AB  - PURPOSE: This study investigated the neural adaptations following submaximal
      isokinetic eccentric strength training of the plantar flexors. The modulation of
      electromyographic (EMG) activity and spinal excitability were compared in the
      soleus muscle (SOL) during isometric, concentric and eccentric maximal voluntary
      contractions (MVC) before and after submaximal isokinetic eccentric training.
      METHODS: Eighteen healthy subjects were divided into a training group (n = 8) and
      a control group (n = 10). The training protocol consisted of sixteen sessions of
      isokinetic eccentric strength training during 8 weeks. Normalized EMG was used to
      assess the activity of SOL and medial gastrocnemius muscle (MG). For SOL, maximal
      Hoffmann reflex (H-reflex) and compound motor potential were evoked during
      isometric, concentric and eccentric actions at rest (Hmax and Mmax, respectively)
      and during MVC (Hsup and Msup, respectively). RESULTS: The results showed that
      the torque and normalized EMG of SOL significantly increased after training
      during eccentric (+20.5 and +28.8 %, respectively) and isometric (+18.2 and +23.0
      %, respectively) MVC (p < 0.05). Hmax/Mmax and Hsup/Msup ratios were not
      significantly modified after training for SOL (p > 0.05), and remained
      significantly depressed during eccentric compared to isometric and concentric
      actions (p < 0.05). In contrast, no significant difference was observed on
      normalized EMG of MG (p > 0.05). CONCLUSIONS: These results suggested that the
      increase in voluntary torque after submaximal isokinetic eccentric training can
      be at least partly ascribed to enhanced neural drive for SOL that does not affect
      the H-reflex pathway.

PMID- 27030129
TI  - Thinking globally, training locally.

PMID- 27030130
TI  - Competency-based medical education: Its time has arrived.

PMID- 27030128
TI  - Clinical, hematological and biochemical alterations in hamster (Mesocricetus
      auratus) experimentally infected with Leishmania infantum through different
      routes of inoculation.
AB  - BACKGROUND: Leishmaniasis remains among the most important parasitic diseases in
      the developing world and visceral leishmaniasis (VL) is the most fatal. The
      hamster Mesocricetus auratus is a susceptible model for the characterization of
      the disease, since infection of hamsters with L. infantum reproduces the clinical
      and pathological features of human VL. In this context, it provides a unique
      opportunity to study VL in its active form. The main goal of this study was to
      evaluate the clinical, biochemical, and hematological changes in male hamsters
      infected through different routes and strains of L. infantum. METHODS: In the
      current study, hamsters (Mesocricetus auratus) were infected with the L. infantum
      strains (WHO/MHOM/BR/74/PP75 and MCAN/BR/2008/OP46) by intradermal,
      intraperitoneal and intracardiac routes. The animals were monitored for a nine
      month follow-up period. RESULTS: The hamsters showed clinical signs similar to
      those observed in classical canine and human symptomatic VL, including
      splenomegaly, severe weight loss, anemia, and leucopenia. Therefore the OP46
      strain was more infective, clinical signs were more frequent and more exacerbated
      in IC group with 80 to 100 % of the animals showing splenomegaly, in the last
      month infection. Additionally, desquamation, hair loss and external mucocutaneous
      lesions and ulcers localized in the snout, accompanied by swelling of the paws in
      all animals, were observed. Consequently, the animals presented severe weight
      loss/cachexia, hunched posture, an inability to eat or drink, and non
      responsiveness to external stimuli. Furthermore, regardless of strain, route of
      inoculum and time assessed, the animals showed renal and hepatic alterations,
      with increased serum levels of urea and creatinine as well as elevated serum
      levels of aspartate aminotransferase and alanine aminotransferase. CONCLUSIONS:
      These results strongly suggest that the inoculation through the intracardiac
      route resulted in a higher severity among infections, especially in the sixth and
      ninth month after infection via intracardiac, exhibited clinical manifestations
      and biochemical/hematological findings similar to human visceral leishmaniasis.
      Therefore, we suggest that this route must be preferentially used in experimental
      infections for pathogenesis studies of VL in the hamster model.

PMID- 27030131
TI  - The effect of continuous hypertonic saline infusion and hypernatremia on
      mortality in patients with severe traumatic brain injury: a retrospective cohort
      study.
AB  - PURPOSE: Hypertonic saline (HTS) is used to control intracranial pressure (ICP)
      in patients with traumatic brain injury (TBI); however, in prior studies, the
      resultant hypernatremia has been associated with increased mortality. We aimed to
      study the effect of HTS on ICP and mortality in patients with severe TBI.
      METHODS: We performed a retrospective cohort study of 231 patients with severe
      TBI (Glasgow Coma Scale [GCS] <= 8) admitted to two neurotrauma units from 2006
      2012. We recorded daily HTS, ICP, and serum sodium (Na) concentration. We used
      Cox proportional regression modelling for hospital mortality and incorporated the
      following time-dependent variables: use of HTS, hypernatremia, and desmopressin
      administration. RESULTS: The mean [standard deviation (SD)] age of patients was
      34 (17) and the median (interquartile range [IQR]) GCS was 6 [3-8]. Hypertonic
      saline was administered as a continuous infusion in 124 of 231 (54%) patients
      over 788 of 2,968 (27%) patient-days. Hypernatremia (Na > 145 mmol.L(-1))
      developed in 151 of 231 (65%) patients over 717 of 2,968 (24%) patients-days. In
      patients who developed hypernatremia, the median [IQR] Na was 146 [142-147]
      mmol.L(-1). Overall hospital mortality was 26% (59 of 231 patients). After
      adjusting for baseline covariates, neither HTS (hazard ratio [HR], 1.07; 95%
      confidence interval [CI], 0.56 to 2.05; P = 0.84) nor hypernatremia (HR, 1.31;
      95% CI, 0.68 to 2.55; P = 0.42) was associated with hospital mortality. There was
      no effect modification by either HTS or hypernatremia on each another. Patients
      who received HTS observed a significant decrease in ICP during their ICU stay
      compared with those who did not receive HTS (4 mmHg; 95% CI, 2 to 6; P < 0.001 vs
      2 mmHg; 95% CI, -1 to 5; P = 0.14). CONCLUSIONS: Hypertonic saline and
      hypernatremia are not associated with hospital mortality in patients with severe
      TBI.

PMID- 27030132
TI  - Publication bias in the anesthesiology literature: shifting the focus from the
      "positive" to the "truth".

PMID- 27030134
TI  - Intrinsic resistance to sunitinib in patients with metastatic renal cell
      carcinoma.
AB  - AIM: Although targeting angiogenesis with vascular endothelial growth factor
      receptor (VEGFR) inhibitors has demonstrated efficacy in the treatment of renal
      cell carcinoma, primary, intrinsic resistance to the VEGFR inhibitor sunitinib is
      not fully understood in a subset of metastatic RCC (mRCC) patients. METHODS:
      Between 2008 and 2012, a total of 134 patients with mRCC were treated with first
      line sunitinib at one of six tertiary centers. Patients in whom progressive
      disease was the best response were classified as the intrinsic resistance group.
      Univariate and multivariate analyses were performed on the recognized baseline
      parameters. RESULTS: Among 134 patients, 33 (25%) intrinsically resistant to
      sunitinib were identified. Multivariate logistic regression analyses revealed
      that the number of metastatic sites (OR = 3.6) and neutrophilia (OR = 7.4) were
      independently associated with development of intrinsic resistance. There were
      significant differences with regard to overall survival (P = 0.001) and
      progression-free survival (P < 0.0001) between the patients with and without
      intrinsic resistance. CONCLUSIONS: Intrinsic resistance to first-line sunitinib
      treatment is associated with a dismal prognosis in mRCC patients. Patients with
      known high-risk factors (poor performance, neutrophilia, elevated lactate
      dehydrogenase) and multiple metastatic sites including the liver may experience a
      limited benefit from sunitinib. Greater understanding of the underlying mechanism
      and molecular biomarkers for detecting intrinsically resistant disease is needed.

PMID- 27030133
TI  - An evolutionary roadmap to the microtubule-associated protein MAP Tau.
AB  - BACKGROUND: The microtubule associated protein Tau (MAPT) promotes assembly and
      interaction of microtubules with the cytoskeleton, impinging on axonal transport
      and synaptic plasticity. Its neuronal expression and intrinsic disorder implicate
      it in some 30 tauopathies such as Alzheimer's disease and frontotemporal
      dementia. These pathophysiological studies have yet to be complemented by
      computational analyses of its molecular evolution and structural models of all
      its functional domains to explain the molecular basis for its conservation
      profile, its site-specific interactions and the propensity to conformational
      disorder and aggregate formation. RESULTS: We systematically annotated public
      sequence data to reconstruct unspliced MAPT, MAP2 and MAP4 transcripts spanning
      all represented genomes. Bayesian and maximum likelihood phylogenetic analyses,
      genetic linkage maps and domain architectures distinguished a nonvertebrate
      outgroup from the emergence of MAP4 and its subsequent ancestral duplication to
      MAP2 and MAPT. These events were coupled to other linked genes such as KANSL1L
      and KANSL and may thus be consequent to large-scale chromosomal duplications
      originating in the extant vertebrate genomes of hagfish and lamprey. Profile
      hidden Markov models (pHMMs), clustered subalignments and 3D structural
      predictions defined potential interaction motifs and specificity determining
      sites to reveal distinct signatures between the four homologous microtubule
      binding domains and independent divergence of the amino terminus. CONCLUSION:
      These analyses clarified ambiguities of MAPT nomenclature, defined the order,
      timing and pattern of its molecular evolution and identified key residues and
      motifs relevant to its protein interaction properties and pathogenic role.
      Additional unexpected findings included the expansion of cysteine-containing,
      microtubule binding domains of MAPT in cold adapted Antarctic icefish and the
      emergence of a novel multiexonic saitohin (STH) gene from repetitive elements in
      MAPT intron 11 of certain primate genomes.

PMID- 27030138
TI  - Breaking Bad News to Togolese Patients.
AB  - The aim of this study was to map Togolese people's positions regarding the
      breaking of bad news to elderly patients. Two hundred eleven participants who had
      in the past received bad medical news were presented with 72 vignettes depicting
      communication of bad news to elderly female patients and asked to indicate the
      acceptability of the physician's conduct in each case. The vignettes were all
      combinations of five factors: (a) the severity of the disease, (b) the patient's
      wishes about disclosure, (c) the level of social support during hospitalization,
      (d) the patient's psychological robustness, and (e) the physician's decision
      about how to communicate the bad news. Five qualitatively different positions
      were found. Two percent of the participants preferred that the physician always
      tell the full truth to both the patient and her relatives, 8% preferred that the
      truth be told depending on the physician's perception of the situation, 15%
      preferred that the physician tell the truth but understood that in some cases
      nondisclosure to the patient was not inappropriate, 33% preferred that the
      physician tell the full truth to the relatives but not as much information to the
      patient, and 42% preferred that the physician tell the full truth to the
      relatives only. These findings present a challenge to European physicians taking
      care of African patients living in Europe or working in African hospitals, and to
      African physicians trained in Europe and now working in their home countries. If
      these physicians respect the imperative of always telling the truth directly to
      their patients, their behavior may trigger anger and considerable
      misunderstanding among African patients and their families.

PMID- 27030135
TI  - Metabotropic Glutamate Receptors and Interacting Proteins in Epileptogenesis.
AB  - Neurotransmitter and receptor systems are involved in different neurological and
      neuropsychological disorders such as Parkinson&#039;s disease, depression,
      Alzheimer's disease and epilepsy. Recent advances in studies of signal
      transduction pathways or interacting proteins of neurotransmitter receptor
      systems suggest that different receptor systems may share the common signal
      transduction pathways or interacting proteins which may be better therapeutic
      targets for development of drugs to effectively control brain diseases. In this
      paper, we reviewed metabotropic glutamate receptors (mGluRs) and their related
      signal transduction pathways or interacting proteins in status epilepticus and
      temporal lobe epilepsy, and proposed some novel therapeutical drug targets for
      controlling epilepsy and epileptogenesis. 

PMID- 27030139
TI  - Selective occupancy of methane by cage symmetry in TBAB ionic clathrate hydrate.
AB  - Methane trapped in the two distinct dodecahedral cages of the ionic clathrate
      hydrate of TBAB was studied by single crystal XRD and MD simulation. The relative
      CH4 occupancies over the cage types were opposite to those of CO2, which
      illustrates the interplay between the cage symmetry and guest shape and dynamics,
      and thus the gas selectivity. 

PMID- 27030137
TI  - Dystonia, lower limb stiffness, and upward gaze palsy in a patient with IgLON5
      antibodies.

PMID- 27030136
TI  - Examining the use of metaphors to understand the experience of community
      treatment orders for patients and mental health workers.
AB  - BACKGROUND: Community Treatment Orders (CTOs) are often complex because of the
      ethical tensions created by an intervention that aims at promoting the patient's
      good through an inherently coercive process. There is limited research that
      examines the complexity of CTOs and how patients on CTOs and workers
      administering CTOs make sense of their experiences. METHODS: The study involved
      in-depth interviews with 8 patients on CTOs and 10 community mental health
      workers in South Australia, to explore how they constructed their experiences of
      CTOs. Critical discourse analysis (CDA) was used to analyse the data, supported
      by NVIVO software. RESULTS: Analysis of the interviews revealed that patients and
      workers experienced the CTO process as multi-dimensional, including some positive
      as well as more negative constructions. The positive metaphor of CTOs as a safety
      net is described, followed by a more detailed description of the metaphors of
      power and control as the dominant themes, with five sub-themes of the CTO as
      control, wake-up, punishment, surveillance, and tranquiliser. DISCUSSION:
      Metaphors are a way that mental health patients and mental health workers
      articulate the nature of CTOs. The language used to construct these metaphors was
      quite different, with patients overwhelmingly experiencing and perceiving CTOs as
      coercive (that is, punishing, controlling and scrutinizing), whereas workers
      tended to perceive them as necessary, beneficial and supportive, despite their
      coerciveness. CONCLUSIONS: By acknowledging the role of metaphors in these
      patients' lives, workers could enhance opportunities to engage these patients in
      more meaningful dialogue about their personal experiences as an alternative to
      practice predominantly focused on risk. Such a dialogue could enhance workers'
      reflection on their work and promote recovery-based practice. More understanding
      of how to promote autonomy, capacity and supported decision-making, and how to
      address the impacts of coercion within care, is needed.

PMID- 27030140
TI  - Reversible Fluorescent Probe for Selective Detection and Cell Imaging of
      Oxidative Stress Indicator Bisulfite.
AB  - In this paper, we report a benzothiazole-functionalized cyanine fluorescence
      probe and demonstrate that it is selectively reactive to bisulfite, an
      intermediate indicator for oxidative stress. The selective reaction can be
      monitored by distinct ratiometric fluorescence variation favorable for cell
      imaging and visualization. The original probe can be regenerated in high yield
      through the elimination of bisulfite from the product by peroxides such as
      hydrogen peroxide, accompanied by fluorescence turning on at 590 nm, showing a
      potential application for the detection of peroxides. We successfully applied
      this probe for fluorescence imaging of bisulfite in cancer cells (MCF-7) treated
      with bisulfite and hydrogen peroxide as well as a selective detection limit of
      0.34 MUM bisulfite in aqueous solution. 

PMID- 27030141
TI  - Large and Anisotropic Linear Magnetoresistance in Single Crystals of Black
      Phosphorus Arising From Mobility Fluctuations.
AB  - Black Phosphorus (BP) is presently attracting immense research interest on the
      global level due to its high mobility and suitable band gap for potential
      application in optoelectronics and flexible devices. It was theoretically
      predicted that BP has a large direction-dependent electrical and magnetotransport
      anisotropy. Investigations on magnetotransport of BP may therefore provide a new
      platform for studying the nature of electron transport in layered materials.
      However, to the best of our knowledge, magnetotransport studies, especially the
      anisotropic magnetoresistance (MR) effect in layered BP, are rarely reported.
      Here, we report a large linear MR up to 510% at a magnetic field of 7 Tesla in
      single crystals of BP. Analysis of the temperature and angle dependence of MR
      revealed that the large linear MR in our sample originates from mobility
      fluctuations. Furthermore, we reveal that the large linear MR of layered BP in
      fact follows a three-dimensional behavior rather than a two-dimensional one. Our
      results have implications to both the fundamental understanding and
      magnetoresistive device applications of BP. 

PMID- 27030142
TI  - Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new
      IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: A Phase 1 study.
AB  - GNbAC1 is a humanized IgG4 monoclonal antibody antagonist of Mulitple Sclerosis
      Retrovirus Envelope (MSRV-Env), a protein that could play a critical role in
      multiple sclerosis. This randomized placebo-controlled dose-escalation study
      evaluated the safety and pharmacokinetics of GNbAC1 in 21 healthy volunteers
      after single intravenous infusion at doses of 6, 18 and 36 mg/kg. Lumbar
      punctures were performed at days 2, 15 or 29 to measure GNbAC1 concentrations in
      cerebrospinal fluid (CSF). GNbAC1 was well tolerated. Serum data show a dose
      linear pharmacokinetics. A mean CSF/serum ratio of 0.12% was observed at Day 2,
      increasing to 0.39% at Day 15 and 0.42% at Day 29. Linear regression analysis
      shows a relationship between GNbAC1 CSF/serum ratio and albumin CSF/serum ratio
      and a relationship at the limit of statistical significance with the timing of
      CSF sampling.

PMID- 27030143
TI  - Single crystalline cylindrical nanowires - toward dense 3D arrays of magnetic
      vortices.
AB  - Magnetic vortex-based media have recently been proposed for several applications
      of nanotechnology; however, because lithography is typically used for their
      preparation, their low-cost, large-scale fabrication is a challenge. One solution
      may be to use arrays of densely packed cobalt nanowires that have been
      efficiently fabricated by electrodeposition. In this work, we present this type
      of nanoscale magnetic structures that can hold multiple stable magnetic vortex
      domains at remanence with different chiralities. The stable vortex state is
      observed in arrays of monocrystalline cobalt nanowires with diameters as small as
      45 nm and lengths longer than 200 nm with vanishing magnetic cross talk between
      closely packed neighboring wires in the array. Lorentz microscopy, electron
      holography and magnetic force microscopy, supported by micromagnetic simulations,
      show that the structure of the vortex state can be adjusted by varying the aspect
      ratio of the nanowires. The data we present here introduce a route toward the
      concept of 3-dimensional vortex-based magnetic memories. 

PMID- 27030144
TI  - Transforming waste biomass with an intrinsically porous network structure into
      porous nitrogen-doped graphene for highly efficient oxygen reduction.
AB  - Porous nitrogen-doped graphene with a very high surface area (1152 m(2) g(-1)) is
      synthesized by a novel strategy using intrinsically porous biomass (soybean
      shells) as a carbon and nitrogen source via calcination and KOH activation. To
      redouble the oxygen reduction reaction (ORR) activity by tuning the doped
      nitrogen content and type, ammonia (NH3) is injected during thermal treatment.
      Interestingly, this biomass-derived graphene catalyst exhibits the unique
      properties of mesoporosity and high pyridine-nitrogen content, which contribute
      to the excellent oxygen reduction performance. As a result, the onset and half
      wave potentials of the new metal-free non-platinum catalyst reach -0.009 V and 
      0.202 V (vs. SCE), respectively, which is very close to the catalytic activity of
      the commercial Pt/C catalyst in alkaline media. Moreover, our catalyst has a
      higher ORR stability and stronger CO and CH3OH tolerance than Pt/C in alkaline
      media. Importantly, in acidic media, the catalyst also exhibits good ORR
      performance and higher ORR stability compared to Pt/C. 

PMID- 27030145
TI  - New native South American Y chromosome lineages.
AB  - Many single-nucleotide polymorphisms (SNPs) in the non-recombining region of the
      human Y chromosome have been described in the last decade. High-coverage
      sequencing has helped to characterize new SNPs, which has in turn increased the
      level of detail in paternal phylogenies. However, these paternal lineages still
      provide insufficient information on population history and demography, especially
      for Native Americans. The present study aimed to identify informative paternal
      sublineages derived from the main founder lineage of the Americas-haplogroup Q
      L54-in a sample of 1841 native South Americans. For this purpose, we used a Y
      chromosomal genotyping multiplex platform and conventional genotyping methods to
      validate 34 new SNPs that were identified in the present study by sequencing,
      together with many Y-SNPs previously described in the literature. We updated the
      haplogroup Q phylogeny and identified two new Q-M3 and three new Q-L54*(xM3)
      sublineages defined by five informative SNPs, designated SA04, SA05, SA02, SA03
      and SA29. Within the Q-M3, sublineage Q-SA04 was mostly found in individuals from
      ethnic groups belonging to the Tukanoan linguistic family in the northwest
      Amazon, whereas sublineage Q-SA05 was found in Peruvian and Bolivian Amazon
      ethnic groups. Within Q-L54*, the derived sublineages Q-SA03 and Q-SA02 were
      exclusively found among Coyaima individuals (Cariban linguistic family) from
      Colombia, while Q-SA29 was found only in Maxacali individuals (Jean linguistic
      family) from southeast Brazil. Furthermore, we validated the usefulness of
      several published SNPs among indigenous South Americans. This new Y chromosome
      haplogroup Q phylogeny offers an informative paternal genealogy to investigate
      the pre-Columbian history of South America.Journal of Human Genetics advance
      online publication, 31 March 2016; doi:10.1038/jhg.2016.26. 

PMID- 27030146
TI  - WDR45 mutations in three male patients with West syndrome.
AB  - West syndrome is an early-onset epileptic encephalopathy characterized by
      clustered spasms with hypsarrhythmia seen on electroencephalogram (EEG). West
      syndrome is genetically heterogeneous, and its genetic causes have not been fully
      elucidated. WD Repeat Domain 45 (WDR45) resides on Xp11.23, and encodes a member
      of the WD repeat protein interacting with phosphoinositides (WIPI) family, which
      is crucial in the macroautophagy pathway. De novo mutations in WDR45 cause beta
      propeller protein-associated neurodegeneration characterized by iron accumulation
      in the basal ganglia. In this study, we performed whole exome sequencing of
      individuals with West syndrome and identified three WDR45 mutations in three
      independent males (patients 1, 2 and 3). Two novel mutations occurred de novo
      (patients 1 and 2) and the remaining mutation detected in a male patient (patient
      3) and his affected sister was inherited from the mother, harboring the somatic
      mutation. The three male patients showed early-onset intractable seizures,
      profound intellectual disability and developmental delay. Their brain magnetic
      resonance imaging scans showed cerebral atrophy. We found no evidence of somatic
      mosaicism in the three male patients. Our findings indicate that hemizygous WDR45
      mutations in males lead to severe epileptic encephalopathy. 

PMID- 27030147
TI  - Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a
      Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency.
AB  - Desbuquois dysplasia type 2 (DBQD2) is a rare recessively inherited skeletal
      genetic disorder characterized by severe prenatal and postnatal growth
      retardation, generalized joint laxity with dislocation of large joints and facial
      dysmorphism. The condition was recently described to result from autosomal
      recessive mutations in XYLT1, encoding the enzyme xylosyltransferase-1. In this
      paper, we report on a Polish patient with DBQD2 who presented with severe short
      stature of prenatal onset, joint laxity, psychomotor retardation and multiple
      radiological abnormalities including short metacarpals, advanced bone age and
      exaggerated trochanters. Endocrinological examinations revealed that sleep
      induced growth hormone (GH) release and GH peak in clonidine- and glucagon
      induced provocative tests as well as insulin-like growth factor 1 (IGF-1) and IGF
      binding protein-3 levels were all markedly decreased, confirming deficiency of GH
      secretion. Bone age, unlikely to GH deficiency, was significantly advanced. To
      establish the diagnosis at a molecular level, we performed whole-exome sequencing
      and bioinformatic analysis in the index patient, which revealed compound
      heterozygous XYLT1 mutations: c.595C>T(p.Gln199*) and c.1651C>T(p.Arg551Cys),
      both of which are novel. Sanger sequencing showed that the former mutation was
      inherited from the healthy mother, whereas the latter one most probably occurred
      de novo. Our study describes the first case of DBQD2 resulting from compound
      heterozygous XYLT1 mutation, expands the mutational spectrum of the disease and
      provides evidence that the severe growth retardation and microsomia observed in
      DBQD2 patients may result not only from the skeletal dysplasia itself but also
      from GH and IGF-1 deficiency. 

PMID- 27030149
TI  - The effects of oxytocin and atosiban on the modulation of heart rate in pregnant
      women.
AB  - OBJECTIVE: To evaluate autonomic modulation of heart rate in pregnant women
      treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist)
      to arrest preterm labor. METHODS: A prospective study with two cohorts: 14
      pregnant women treated with atosiban for premature uterine contractions, and 28
      women undergoing induction of labor with oxytocin. Computerized analyses of the
      electrocardiogram were performed with spectral and nonlinear dynamic analyses.
      RESULTS: Atosiban did not alter any of the variables associated with heart rate
      variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p <
      0.05) and a significant increase in all spectral variables studied (p < 0.01).
      CONCLUSIONS: Atosiban has no adverse effects on the cardiovascular system or the
      modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent
      bradycardic effect and an increase in the spectral power, thus should be used
      with caution in certain pregnant women.

PMID- 27030150
TI  - Letting the sunshine in?

PMID- 27030151
TI  - Potential for increased stem-cell donor recruitment in India.

PMID- 27030152
TI  - To begin at the beginning: sickle cell disease in Africa.

PMID- 27030153
TI  - B-cell receptor stereotypy and chronic lymphocytic leukaemia.

PMID- 27030154
TI  - Globalisation of clinical trials and ethics of benefit sharing.

PMID- 27030155
TI  - HLA match likelihoods for Indian patients seeking unrelated donor transplantation
      grafts: a population-based study.
AB  - BACKGROUND: For patients who do not have a suitable human leukocyte antigen (HLA)
      matched family donor, unrelated donor registries of adult volunteers and banked
      umbilical cord blood (UCB) units provide the potential for successful
      haemopoietic stem-cell transplantation. The size and genetic composition of such
      registries determines the proportion of patients who will be able to find a
      suitable match. We aimed to assess the proportion of positive matches for Indian
      patients. METHODS: Using HLA data from ten existing donor and UCB registries and
      clinical transplant centres in India, we built population-based genetic models
      for 14 Indian regions to model Indian registry growth to predict the likelihood
      of identifying a suitable donor-either an adult donor or UCB-for Indian patients.
      We computed ranking tables of the top ten haplotypes in each regional group and
      compared these with four US samples from the National Marrow Donor Program (NMDP)
      registry. FINDINGS: The mean proportion of individuals who would have a 10/10
      adult donor match within India ranged from 14.4% with a registry size of 25 000
      to 60.6% with a registry size of 1 000 000. Only when donor registries increased
      to 250 000 did the match rate within India exceed that found by searching the US
      NMDP registry combined with an Indian registry of 25 000 donors. The proportion
      of matches increased logarithmically with increased registry size (R(2)=0.993).
      For a UCB registry size of 25 000, 96.4% of individuals would find a 4/6 match;
      however, only 18.3% would have a 6/6 match. INTERPRETATION: Serial match
      modelling and follow-up comparisons can identify the relative and progressively
      greater value of an India-based donor registry and UCB banking network to serve
      the Indian population. Understanding regional HLA haplotype diversity could guide
      registry growth and maximise benefit to patients. Similar modelling could guide
      planning for the needs of other ethnically distinct populations. FUNDING:
      University of Minnesota and the Indian Council for Medical Research.

PMID- 27030156
TI  - Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a
      multinational, prospective, cross-sectional study.
AB  - BACKGROUND: Chronic kidney disease is one of the leading causes of mortality in
      patients with sickle cell disease. However, it has been almost exclusively
      studied in patients with the SS phenotype and in high-income countries, despite
      more than 80% of patients living in Africa. We looked for the determinants of
      glomerulopathy in a multinational cohort of patients with sickle cell disease of
      different phenotypes in sub-Saharan Africa. METHODS: In the CADRE cohort, we
      prospectively included patients 3 years and older with sickle cell disease of all
      haemoglobin phenotypes in Cameroon, Cote d'Ivoire, Mali, and Senegal. All
      individuals were assessed at steady state. The main outcome of interest was
      albuminuria defined as a urine albumin-to-creatinine ratio of greater than 30
      mg/g. We investigated the clinical and biological determinants (including
      haemolysis markers) of albuminuria in two main phenotype groups (SS and Sbeta(0);
      SC and Sbeta(+)) with further stratification by age and country. FINDINGS: The
      study is ongoing because of follow-up. 2582 patients with sickle cell disease
      were included (1776 SS, 136 Sbeta(0), 511 SC, and 159 Sbeta(+)). 644 patients
      with the SS and Sbeta(0) phenotypes (33.7%, 95% CI 31.6-35.8) and 110 with the SC
      and Sbeta(+) phenotypes (16.4%, 13.6-19.2) had albuminuria. In the SS and
      Sbeta(0) group, albuminuria was detected in 144 (27%) of 527 children younger
      than 10 years and its frequency increased with age (29 [48%] of 60 patients aged
      >40 years). Multivariable analysis showed that albuminuria was associated with
      age (odds ratio 1.43, 95% CI 1.20-1.71; p<0.0001), female sex (1.35, 1.02-1.82;
      p=0.045), low haemoglobin (0.79, 0.66-0.93; p=0.006), high lactate dehydrogenase
      concentrations (1.33, 1.14-1.58; p=0.0009), and, using Cote d'Ivoire as the
      reference, Mali (2.49, 1.64-3.79; p=0.042) and Cameroon (1.59, 1.01-2.51;
      p=0.0007) in patients with the SS and Sbeta(0) phenotypes. The magnitude of the
      association of albuminuria with haemoglobin and lactate dehydrogenase
      concentrations increased with age. In the SC and Sbeta(+) patients, only low
      haemoglobin (0.69, 0.48-0.97; p=0.029), high blood pressure (1.63, 1.17-2.27;
      p=0.0017), and Mali (3.75, 1.75-8.04; p<0.0001) were associated with albuminuria.
      INTERPRETATION: Hyperhaemolysis is associated with albuminuria, with an age
      dependent effect, in the SS and Sbeta(0) phenotypes only, suggesting a different
      pathological mechanism for glomerular disease in the patients with SC and
      Sbeta(+) phenotypes. However, both phenotypes are associated with a high
      prevalence of albuminuria in childhood. Therefore, screening for albuminuria is
      advised in African children with sickle cell disease to detect early renal
      damage. FUNDING: Paris Cite Sorbonne University (GrEX project) and Cardiology and
      Development.

PMID- 27030157
TI  - Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic
      lymphocytic leukaemia: a retrospective multicentre study.
AB  - BACKGROUND: About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi
      identical B-cell receptor immunoglobulins and can be assigned to distinct
      stereotyped subsets. Although preliminary evidence suggests that B-cell receptor
      immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has
      never been explored in a systematic manner or in a cohort of adequate size that
      would enable clinical conclusions to be drawn. METHODS: For this retrospective,
      multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data
      were available. These patients were followed up in 15 academic institutions
      throughout Europe (in Czech Republic, Denmark, France, Greece, Italy,
      Netherlands, Sweden, and the UK) and the USA, and data were collected between
      June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical
      implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular
      focus on 14 major stereotyped subsets comprising cases expressing unmutated (U
      CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary
      outcome of our analysis was time to first treatment, defined as the time between
      diagnosis and date of first treatment. FINDINGS: 2878 patients were assigned to a
      stereotyped subset, of which 1122 patients belonged to one of 14 major subsets.
      Stereotyped subsets showed significant differences in terms of age, sex, disease
      burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic
      significance. Patients within a specific subset generally followed the same
      clinical course, whereas patients in different stereotyped subsets-despite having
      the same immunoglobulin heavy variable gene and displaying similar immunoglobulin
      mutational status-showed substantially different times to first treatment. By
      integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4)
      into the well established Dohner cytogenetic prognostic model, we showed these,
      which collectively account for around 7% of all cases of CLL and represent both U
      CLL and M-CLL, constituted separate clinical entities, ranging from very indolent
      (subset 4) to aggressive disease (subsets 1 and 2). INTERPRETATION: The molecular
      classification of chronic lymphocytic leukaemia based on B-cell receptor
      immunoglobulin stereotypy improves the Dohner hierarchical model and refines
      prognostication beyond immunoglobulin mutational status, with potential
      implications for clinical decision making, especially within prospective clinical
      trials. FUNDING: European Union; General Secretariat for Research and Technology
      of Greece; AIRC; Italian Ministry of Health; AIRC Regional Project with
      Fondazione CARIPARO and CARIVERONA; Regione Veneto on Chronic Lymphocytic
      Leukemia; Nordic Cancer Union; Swedish Cancer Society; Swedish Research Council;
      and National Cancer Institute (NIH).

PMID- 27030158
TI  - Parental and Adolescent Perceptions of Neighborhood Safety Related to
      Adolescents' Physical Activity in Their Neighborhood.
AB  - PURPOSE: The purpose of this study was to examine the association between
      adolescent and parental perceptions of neighborhood safety and adolescents'
      physical activity in multiple locations and to investigate the moderating effect
      of sex within this association. METHOD: This cross-sectional study was conducted
      with 928 adolescents aged 12 to 16 years old and 1 of their parents. Adolescents
      and parents reported their perceptions of neighborhood safety (traffic safety,
      pedestrian safety, crime safety, and stranger danger safety). Adolescents
      reported how often they were physically active in multiple locations (physical
      activity in the neighborhood, in parks, and for active transport). Mixed-effects
      linear regression models were used to investigate these associations while
      controlling for demographics and the Walkability Index. RESULTS: Parent-perceived
      crime safety was positively associated with adolescents' physical activity in
      parks (B = .094, p = .024). Parent-perceived traffic safety was positively
      associated with adolescents' reported physical activity in the neighborhood (B =
      .186, p = .014). Adolescents' physical activity for active transport was
      positively associated with parent-perceived traffic safety (B = .179, p = .001),
      stranger danger safety (B = .110, p = .013), and crime safety (B = .077, p =
      .035). There were 2 interactions by sex on the relation between adolescent
      traffic safety perception and parent pedestrian safety perception in the
      neighborhood and adolescents' physical activity in parks (i.e., statistically
      significant only for boys). CONCLUSIONS: Parents' perceptions of traffic,
      stranger danger, and crime safety were all related to adolescents' active
      transportation. Multiple safety concerns may be motivating parents to restrict
      adolescent mobility by walking and bicycling.

PMID- 27030159
TI  - Transition-Metal Doped Ceria Microspheres with Nanoporous Structures for CO
      Oxidation.
AB  - Catalytic oxidation of carbon monoxide (CO) is of great importance in many
      different fields of industry. Until now it still remains challenging to use non
      noble metal based catalysts to oxidize CO at low temperature. Herein, we report a
      new class of nanoporous, uniform, and transition metal-doped cerium (IV) oxide
      (ceria, CeO2) microsphere for CO oxidation catalysis. The porous and uniform
      microsphere is generated by sacrificed polymer template. Transition-metals, like
      Cu, Co, Ni, Mn and Fe, were doped into CeO2 microspheres. The combination of
      hierarchical structure and metal doping afford superior catalytic activities of
      the doped ceria microspheres, which could pave a new way to advanced non-precious
      metal based catalysts for CO oxidation. 

PMID- 27030160
TI  - The cutting of ultrathin sections with the thickness less than 20 nm from
      biological specimens embedded in resin blocks.
AB  - Low voltage electron microscopes working in transmission mode, like LVEM5 (Delong
      Instruments, Czech Republic) working at accelerating voltage 5 kV or scanning
      electron microscope working in transmission mode with accelerating voltage below
      1 kV, require ultrathin sections with the thickness below 20 nm. Decreasing of
      the primary electron energy leads to enhancement of image contrast, which is
      especially useful in the case of biological samples composed of elements with low
      atomic numbers. As a result treatments with heavy metals, like post-fixation with
      osmium tetroxide or ultrathin section staining, can by omitted. The disadvantage
      is reduced penetration ability of incident electrons influencing the usable
      thickness of the specimen resulting in the need of ultrathin sections of under 20
      nm thickness. In this study we want to answer basic questions concerning the
      cutting of extremely ultrathin sections: Is it possible routinely and
      reproducibly to cut extremely thin sections of biological specimens embedded in
      commonly used resins with contemporary ultramicrotome techniques and under what
      conditions? Microsc. Res. Tech. 79:512-517, 2016. (c) 2016 Wiley Periodicals,
      Inc. 

PMID- 27030161
TI  - The complete mitochondrial genome of Orthocoelium streptocoelium (Digenea:
      Paramphistomidae) for comparison with other digeneans.
AB  - Orthocoelium streptocoelium is a common paramphistome species parasitizing the
      rumen and/or reticulum of small ruminants, leading to significant losses. This
      study first determined the complete mitochondrial (mt) genome of O.
      streptocoelium. The complete mt genome of O. streptocoelium was amplified,
      sequenced, assembled, analysed and then compared with those of other digeneans.
      The entire mt genome of O. streptocoelium is 13,800 bp in length, which is
      smaller than those of other digeneans except for Opisthorchis viverrini. This mt
      genome contains 12 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA
      genes and two non-coding regions. The arrangement of the O. streptocoelium mt
      genome is the same as those of other digeneans except for Schistosoma haematobium
      and Schistosoma spindale. Phylogenetic analyses based on concatenated amino acid
      sequences of the 12 protein-coding genes representing 16 digeneans were conducted
      to assess the relationship of O. streptocoelium with other digeneans. The result
      indicated that O. streptocoelium is closely related to Paramphistomum cervi and
      Fischoederius elongates, which is in accordance with their relationships by
      taxonomy. This complete mt genome of O. streptocoelium enriched the mitochondrial
      genome data of paramphistomes and provided important molecular markers for
      diagnostics and studies of population variation, epidemiology, ecology and
      evolution of O. streptocoelium and other digeneans.

PMID- 27030162
TI  - Topical delivery of diclofenac into and across equine skin from a novel liquid
      diclofenac epolamine formulation.
AB  - The aim was to investigate diclofenac delivery into and across equine skin in
      vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP;
      1.3%) formulation and to compare the results to those of Surpass(r) (1%
      diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac
      sodium. Skin was harvested from the lower legs of Freiberger geldings immediately
      after slaughter and sliced to a thickness of ~2 mm. Skin samples were divided
      into two groups [Group 1: 1 year old (n = 2) and Group 2: 6-8 years old (n = 3)].
      Cumulative permeation of diclofenac in Groups 1 and 2 after 24 h using diclofenac
      sodium solution was 1.91 +/- 0.27 and 1.76 +/- 0.34 MUg/cm2 , respectively. The
      values for Surpass(r) and DIC-EP were 3.2 +/- 0.8/3.3 +/- 0.7 MUg/cm2 and 230 +/-
      59/89.2 +/- 32.5 MUg/cm2 , respectively. Thus, diclofenac permeation from DIC-EP
      was significantly greater and appeared to show an age-dependent effect.
      Mathematical modelling showed that the DIC-EP formulation significantly increased
      diclofenac partitioning into the skin and a linear correlation was observed
      between steady-state flux and the partition parameter. Greater skin deposition of
      diclofenac was also observed with DIC-EP. These preliminary results suggest that
      the DIC-EP formulation may be effective in treating inflammatory conditions in
      horses.

PMID- 27030163
TI  - Specific delivery of an immunosuppressive drug to splenic B cells by antigen
      modified liposomes and its antiallergic effect.
AB  - BACKGROUND: Use of the reverse targeting drug delivery system (RT-DDS) is a new
      targeting strategy based on the specific delivery of drugs to immune cells in
      antigen-sensitized animals by using antigen-modified liposomes, and it is
      expected to be a curative treatment for allergic diseases. PURPOSE: Herein, we
      prepared ovalbumin (OVA)-modified liposomes encapsulating the immunosuppressive
      drug FK506 (OVA-LipFK) and aimed to demonstrate the delivery selectivity of the
      liposomes to splenic B cells, and its antiallergic effect in an OVA-sensitized
      allergic model mouse. METHODS: Fluorescently labeled OVA-LipFK was intravenously
      injected into OVA-sensitized mice, and the intrasplenic localization of liposomes
      was observed. The antiallergic effect of OVA-LipFK in OVA-sensitized mice was
      examined by measuring the blood levels of OVA-specific IgE and IgG antibodies.
      RESULTS AND DISCUSSION: OVA-LipFK was co-localized to not only B cells but also
      germinal centers, in the spleen of OVA-sensitized mice. However, there was no
      accumulation of unmodified liposomes encapsulating FK506 (LipFK) in the splenic B
      cell area. In a therapeutic study, OVA-LipFK significantly suppressed the
      production of both OVA-specific IgE and IgG antibodies in OVA-sensitized mice
      after the animals had been boosted with OVA, whereas LipFK showed little
      antiallergic effect. CONCLUSIONS: The present study suggested that the
      introduction of RT-DDS for use with immunosuppressive drugs could be useful for
      the treatment of allergic diseases.

PMID- 27030164
TI  - Scleral and corneal xanthomatous inflammation in a gray mouse lemur (Microcebus
      murinus).
AB  - Bilateral multifocal corneal opacity was detected in a 4.5-year-old male captive
      gray mouse lemur (Microcebus murinus) without other clinical ocular changes.
      Histopathological examination revealed a severe diffuse granulomatous scleritis
      and focal keratitis with intralesional cholesterol, consistent with xanthomatous
      inflammation. This is the first report of xanthomatous inflammation in a gray
      mouse lemur. This condition may be the result of systemic factors (lipid
      metabolism disorders) and/or local predisposing factors such as hemorrhage or
      inflammation. The pathogenesis in this case could not be fully determined.
      Further studies on lemurs are required for a better understanding of their lipid
      metabolism, as well as for diagnosing and evaluating the incidence of
      xanthomatous inflammation in these species.

PMID- 27030165
TI  - Effects of conformational ordering on protein/polyelectrolyte electrostatic
      complexation: ionic binding and chain stiffening.
AB  - Coupling of electrostatic complexation with conformational transition is rather
      general in protein/polyelectrolyte interaction and has important implications in
      many biological processes and practical applications. This work studied the
      electrostatic complexation between kappa-carrageenan (kappa-car) and type B
      gelatin, and analyzed the effects of the conformational ordering of kappa-car
      induced upon cooling in the presence of potassium chloride (KCl) or
      tetramethylammonium iodide (Me4NI). Experimental results showed that the effects
      of conformational ordering on protein/polyelectrolyte electrostatic complexation
      can be decomposed into ionic binding and chain stiffening. At the initial stage
      of conformational ordering, electrostatic complexation can be either suppressed
      or enhanced due to the ionic bindings of K(+) and I(-) ions, which significantly
      alter the charge density of kappa-car or occupy the binding sites of gelatin.
      Beyond a certain stage of conformational ordering, i.e., helix content theta >
      0.30, the effect of chain stiffening, accompanied with a rapid increase in helix
      length zeta, becomes dominant and tends to dissociate the electrostatic
      complexation. The effect of chain stiffening can be theoretically interpreted in
      terms of double helix association. 

PMID- 27030166
TI  - Opioids for the palliation of refractory breathlessness in adults with advanced
      disease and terminal illness.
AB  - BACKGROUND: Breathlessness is a common and disabling symptom which affects many
      people with advanced cardiorespiratory disease and cancer. The most effective
      treatments are aimed at treating the underlying disease. However, this may not
      always be possible, and symptomatic treatment is often required in addition to
      maximal disease-directed therapy. Opioids are increasingly being used to treat
      breathlessness, although their mechanism of action is still not completely known.
      A few good sized, high quality trials have been conducted in this area.
      OBJECTIVES: To determine the effectiveness of opioid drugs in relieving the
      symptom of breathlessness in people with advanced disease due to malignancy,
      respiratory or cardiovascular disease, or receiving palliative care for any other
      disease. SEARCH METHODS: We performed searches on CENTRAL, MEDLINE, EMBASE,
      CINAHL, and Web of Science up to 19 October 2015. We handsearched review
      articles, clinical trial registries, and reference lists of retrieved articles.
      SELECTION CRITERIA: We included randomised double-blind controlled trials that
      compared the use of any opioid drug against placebo or any other intervention for
      the relief of breathlessness. The intervention was any opioid, given by any
      route, in any dose. DATA COLLECTION AND ANALYSIS: We imported studies identified
      by the search into a reference manager database. We retrieved the full-text
      version of relevant studies, and two review authors independently extracted data.
      The primary outcome measure was breathlessness and secondary outcome measures
      included exercise tolerance, oxygen saturations, adverse events, and mortality.
      We analysed all studies together and also performed subgroup analyses, by route
      of administration, type of opioid administered, and cause of breathlessness.
      Where appropriate, we performed meta-analysis. We assessed the evidence using the
      Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      approach and created three 'Summary of findings' tables. MAIN RESULTS: We
      included 26 studies with 526 participants. We assessed the studies as being at
      high or unclear risk of bias overall. We only included randomised controlled
      trials (RCTs), although the description of randomisation was incomplete in some
      included studies. We aimed to include double blind RCTs, but two studies were
      only single blinded. There was inconsistency in the reporting of outcome
      measures. We analysed the data using a fixed-effect model, and for some outcomes
      heterogeneity was high. There was a risk of imprecise results due to the low
      numbers of participants in the included studies. For these reasons we downgraded
      the quality of the evidence from high to either low or very low.For the primary
      outcome of breathlessness, the mean change from baseline dyspnoea score was 0.09
      points better in the opioids group compared to the placebo group (ranging from a
      0.36 point reduction to a 0.19 point increase) (seven RCTs, 117 participants,
      very low quality evidence). A lower score indicates an improvement in
      breathlessness. The mean post-treatment dyspnoea score was 0.28 points better in
      the opioid group compared to the placebo group (ranging from a 0.5 point
      reduction to a 0.05 point increase) (11 RCTs, 159 participants, low quality
      evidence).The evidence for the six-minute walk test (6MWT) was conflicting. The
      total distance in 6MWT was 28 metres (m) better in the opioids group compared to
      placebo (ranging from 113 m to 58 m) (one RCT, 11 participants, very low quality
      evidence). However, the change in baseline was 48 m worse in the opioids group
      (ranging from 36 m to 60 m) (two RCTs, 26 participants, very low quality
      evidence).The adverse effects reported included drowsiness, nausea and vomiting,
      and constipation. In those studies, participants were 4.73 times more likely to
      experience nausea and vomiting compared to placebo, three times more likely to
      experience constipation, and 2.86 times more likely to experience drowsiness
      (nine studies, 162 participants, very low quality evidence).Only four studies
      assessed quality of life, and none demonstrated any significant change. AUTHORS'
      CONCLUSIONS: There is some low quality evidence that shows benefit for the use of
      oral or parenteral opioids to palliate breathlessness, although the number of
      included participants was small. We found no evidence to support the use of
      nebulised opioids. Further research with larger numbers of participants, using
      standardised protocols and with quality of life measures included, is needed.

PMID- 27030167
TI  - Decoherence spectroscopy with individual two-level tunneling defects.
AB  - Recent progress with microfabricated quantum devices has revealed that an
      ubiquitous source of noise originates in tunneling material defects that give
      rise to a sparse bath of parasitic two-level systems (TLSs). For superconducting
      qubits, TLSs residing on electrode surfaces and in tunnel junctions account for a
      major part of decoherence and thus pose a serious roadblock to the realization of
      solid-state quantum processors. Here, we utilize a superconducting qubit to
      explore the quantum state evolution of coherently operated TLSs in order to shed
      new light on their individual properties and environmental interactions. We
      identify a frequency-dependence of TLS energy relaxation rates that can be
      explained by a coupling to phononic modes rather than by anticipated mutual TLS
      interactions. Most investigated TLSs are found to be free of pure dephasing at
      their energy degeneracy points, around which their Ramsey and spin-echo dephasing
      rates scale linearly and quadratically with asymmetry energy, respectively. We
      provide an explanation based on the standard tunneling model, and identify
      interaction with incoherent low-frequency (thermal) TLSs as the major mechanism
      of the pure dephasing in coherent high-frequency TLS. 

PMID- 27030169
TI  - A visionary scientist selects clinicians for clinical research.

PMID- 27030168
TI  - GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION
      RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.
AB  - INTRODUCTION: We tested the relationship between genotype, gene expression and
      suicidal behavior and major depressive disorder (MDD) in live subjects and
      postmortem samples for three genes, associated with the hypothalamic-pituitary
      adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5),
      Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor
      (NR3C1). MATERIALS AND METHODS: Single-nucleotide polymorphisms (SNPs) and
      haplotypes were tested for association with suicidal behavior and MDD in a live
      (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and
      isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression
      quantitative trait loci (eQTL) relationships were examined using a public
      database (UK Brain Expression Consortium). RESULTS: We identified a haplotype
      within the FKBP5 gene, present in 47% of the live subjects, which was associated
      with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs
      on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment
      association with attempted suicide, and two SNPs of SKA2 with suicide death, but
      none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs
      were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript
      had lower expression in suicide relative to nonsuicide sudden death cases (b = 
      0.48, SE = 0.12, t = -4.02, adjusted P = .004). CONCLUSION: We have identified an
      association of FKBP5 haplotype with risk of suicide attempt and found an
      association between suicide and altered NR3C1 gene expression in the pFCTX. Our
      findings further implicate hypothalamic pituitary axis dysfunction in suicidal
      behavior.

PMID- 27030170
TI  - High-performance detection of somatic D-loop mutation in urothelial cell
      carcinoma patients by polymorphism ratio sequencing.
AB  - Utilizing a polymorphism ratio sequencing platform, we performed a complete
      somatic mutation analysis of the mitochondrial D-loop region in 14 urothelial
      cell carcinomas. A total of 28 somatic mutations, all heteroplasmic, were
      detected in 8 of 14 individuals (57.1 %). Insertion/deletion changes in unstable
      mono- and dinucleotide repeat segments comprise the most pervasive class of
      mutations (9 of 28), while two recurring single-base substitution loci were
      identified. Seven variants, mostly insertion/deletions, represent population
      shifts from a heteroplasmic germline toward dominance in the tumor. In four
      cases, DNA from matched urine samples was similarly analyzed, with all somatic
      variants present in associated tumors readily detectable in the bodily fluid.
      Consistent with previous findings, mutant populations in urine were similar to
      those detected in tumor and in three of four cases were more prominent in urine.
      KEY MESSAGES: PRS accurately detects high mtDNA mutations in UCCs and their body
      fluids. mtDNA mutations are universally heteroplasmic and often appear at low
      levels. The PRS technology could be a viable approach to develop mitochondrial
      biomarkers.

PMID- 27030171
TI  - Facile preparation of beta-/gamma-MgH2 nanocomposites under mild conditions and
      pathways to rapid dehydrogenation.
AB  - A magnesium hydride composite with enhanced hydrogen desorption kinetics can be
      synthesized via a simple wet chemical route by ball milling MgH2 with LiCl as an
      additive at room temperature followed by tetrahydrofuran (THF) treatment under an
      Ar atmosphere. The as-synthesized composite comprises ca. 18 mass% orthorhombic
      gamma-MgH2 and 80 mass% tetragonal beta-MgH2 as submicron-sized particles. The
      beta-/gamma-MgH2 nanocomposite exhibits a dehydrogenation capacity of 6.6 wt% and
      starts to release hydrogen at ~260  degrees C; ca. 140  degrees C lower than that
      of commercial MgH2. The apparent activation energy for dehydrogenation is 115 +/-
      3 kJ mol(-1), which is ca. 46% lower than that of commercial MgH2. Analysis
      suggests that the meta-stable gamma-MgH2 component either directly dehydrogenates
      exothermically or first transforms into stable beta-MgH2 very close to the
      dehydrogenation onset. The improved hydrogen release performance can be
      attributed both to the existence of the MgH2 nanostructure and to the presence of
      gamma-MgH2.

PMID- 27030172
TI  - High population attributable fractions of myocardial infarction associated with
      waist-hip ratio.
AB  - OBJECTIVE: To estimate population attributable fractions (PAF) of acute
      myocardial infarction (AMI) associated with anthropometric measures by sex and
      age. METHODS: The Cohort of Norway study identified 140,790 participants free of
      cardiovascular disease, 1994-2003. Participants were followed for AMI through
      2009 by record linkages through the Cardiovascular Disease in Norway Project.
      PAFs were adjusted for age, smoking, systolic blood pressure, diabetes, and the
      ratio of total cholesterol to high-density lipoprotein cholesterol. RESULTS: The
      PAFs associated with a waist-hip ratio (WHR) in the top two quintiles were 26.1%
      (95% confidence interval, CI 14.6-36.1) for middle-aged women (<60 years, mean of
      41 years) and 9.3% (95% CI 3.0-15.1) for similarly aged men after adjustment for
      body mass index (BMI) and conventional risk factors. However, PAFs associated
      with anthropometric measures in elderly participants (>= 60 years, mean of 70
      years) were non-significant in multivariable analyses. Also, WHR was a
      significant predictor of AMI among men and women without an enlarged waist
      circumference (<102 cm for men and < 88 cm for women) in adjusted analyses.
      CONCLUSIONS: WHR measurements could improve identification of at-risk individuals
      above and beyond that of conventional risk factors, BMI, or an enlarged waist
      circumference.

PMID- 27030173
TI  - BAY 81-8973, a full-length recombinant factor VIII: results from an International
      comparative laboratory field study.
AB  - INTRODUCTION: BAY 81-8973 is a full-length, unmodified, recombinant human factor
      VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated
      recombinant FVIII but produced with certain more advanced manufacturing
      technologies. AIM: This global laboratory study evaluated variability in
      measurement of BAY 81-8973 using one-stage and chromogenic assays compared with
      antihaemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM;
      Advate((r)) ) under assay conditions routinely used in clinical laboratories.
      METHODS: BAY 81-8973 or rAHF-PFM was spiked into FVIII-deficient plasma at 0.043
      (low), 0.375 (medium) and 0.865 (normal) IU mL(-1) . Participating laboratories
      analysed blinded samples and normal plasma in triplicate using their routine
      assay, reagents and standards. Results were analysed for intra- and
      interlaboratory variability. RESULTS: Forty-one laboratories in 11 countries
      participated in the study. One-stage assay and chromogenic assays were used by 40
      and 10 laboratories, respectively; 9 laboratories used both assays.
      Intralaboratory variability was <11% for both assays and both products at all
      concentrations. Interlaboratory variability was highest at the low concentration
      in the chromogenic and one-stage assay for BAY 81-8973 (60.0% and 33.7%,
      respectively) and rAHF-PFM (51.0% and 30.8%) and was lowest at the normal
      concentration (BAY 81-8973, 5.4% and 14.0%; rAHF-PFM, 5.8% and 12.4%), which was
      similar to the plasma control (6.6% and 10.3%). The chromogenic:one-stage assay
      ratio ranged from 0.95 (low concentration) to 1.10 (normal concentration) for BAY
      81-8973 and 0.96-1.18 for rAHF-PFM. CONCLUSIONS: BAY 81-8973 can be accurately
      measured in plasma using the one-stage and chromogenic assays routinely used in
      clinical laboratories without a product-specific standard.

PMID- 27030174
TI  - Effect of chronotype on emotional processing and risk taking.
AB  - There is increasing evidence to suggest that late chronotypes are at increased
      risk for depression. The putative psychological mechanisms underpinning this
      risk, however, have not been fully explored. The aim of the present study was to
      examine whether, similar to acutely depressed patients and other "at risk"
      groups, late chronotype individuals display biases in tasks assaying emotional
      face recognition, emotional categorisation, recognition and recall and attention.
      Late chronotype was associated with increased recognition of sad facial
      expressions, greater recall and reduced latency to correctly recognise previously
      presented negative personality trait words and reduced allocation of attentional
      resources to happy faces. The current results indicate that certain negative
      biases in emotional processing are present in late chronotypes and may, in part,
      mediate the vulnerability of these individuals to depression. Prospective studies
      are needed to establish whether the cognitive vulnerabilities reported here
      predict subsequent depression. 

PMID- 27030175
TI  - Heparin binding preference and structures in the fibroblast growth factor family
      parallel their evolutionary diversification.
AB  - The interaction of a large number of extracellular proteins with heparan sulfate
      (HS) regulates their transport and effector functions, but the degree of
      molecular specificity underlying protein-polysaccharide binding is still debated.
      The 15 paracrine fibroblast growth factors (FGFs) are one of the paradigms for
      this interaction. Here, we measure the binding preferences of six FGFs (FGF3,
      FGF4, FGF6, FGF10, FGF17, FGF20) for a library of modified heparins, representing
      structures in HS, and model glycosaminoglycans, using differential scanning
      fluorimetry. This is complemented by the identification of the lysine residues in
      the primary and secondary binding sites of the FGFs by a selective labelling
      approach. Pooling these data with previous sets provides good coverage of the FGF
      phylogenetic tree, deduced from amino acid sequence alignment. This demonstrates
      that the selectivity of the FGFs for binding structures in sulfated
      polysaccharides and the pattern of secondary binding sites on the surface of FGFs
      follow the phylogenetic relationship of the FGFs, and so are likely to be the
      result of the natural selection pressures that led to the expansion of the FGF
      family in the course of the evolution of more complex animal body plans. 

PMID- 27030177
TI  - [The calcium-regulating system and recurrent peptic ulcer].
AB  - AIM: To elucidate the functional state and value of the calcium-regulating
      system, calcium and phosphorus metabolism in the pathogenesis and sanogenesis of
      peptic ulcer (PU); to define the possible ways to correct shifts found in the
      treatment of disease relapse, by affecting the different levels of their
      disorders. SUBJECTS AND METHODS: A total of 220 patients with recurrent PU were
      examined by determining the blood levels of parathyrin, calcitonin, calcium and
      phosphorus, as well as gastric secretory and motor functions. RESULTS: Recurrent
      PU was accompanied by a considerable increase in the blood concentration of
      parathyroid hormone and calcium, a slight rise in that of calcitonin, and a
      significant reduction in that of phosphorus. These changes were attended by a
      substantial increase in gastric acid- and pepsinogen-forming functions, a
      decrease in the production of gastric mucoproteins, and hypermotor dyskinesia.
      The use of calcitrin, nifedipine, and etidronic acid, which eliminate dysfunction
      of the calcium-regulating system at different levels of its impairments, leads to
      a significant reduction in the time of alleviation of the clinical and endoscopic
      manifestations of a recurrence. CONCLUSION: Recurrent PU runs in the presence of
      calcium-regulating system dysfunction. Incorporation of the thyroid C-cell
      hormone preparation calcitrin, the slow calcium-channel blocker nifedipine, and
      etidronic acid bisphosphonate into a complex of treatment for a disease
      recurrence is pathogenetically sound and clinically effective.

PMID- 27030176
TI  - Acute stress is detrimental to heart regeneration in zebrafish.
AB  - Psychological stress is one of the factors associated with human cardiovascular
      disease. Here, we demonstrate that acute perceived stress impairs the natural
      capacity of heart regeneration in zebrafish. Beside physical and chemical
      disturbances, intermittent crowding triggered an increase in cortisol secretion
      and blocked the replacement of fibrotic tissue with new myocardium.
      Pharmacological simulation of stress by pulse treatment with
      dexamethasone/adrenaline reproduced the regeneration failure, while inhibition of
      the stress response with anxiolytic drugs partially rescued the regenerative
      process. Impaired heart regeneration in stressed animals was associated with a
      reduced cardiomyocyte proliferation and with the downregulation of several genes,
      includingigfbp1b, a modulator of IGF signalling. Notably, daily stress induced a
      decrease in Igf1r phosphorylation. As cardiomyocyte proliferation was decreased
      in response to IGF-1 receptor inhibition, we propose that the stress-induced
      cardiac regenerative failure is partially caused by the attenuation of IGF
      signalling. These findings indicate that the natural regenerative ability of the
      zebrafish heart is vulnerable to the systemic paracrine stress response. 

PMID- 27030178
TI  - [Gastric and duodenal secretory and motor-evacuatory activity in patients with
      gastroesophageal reflux disease associated with different types of reflux].
AB  - AIM: To estimate esophageal and gastric pH values on an empty stomach and after
      stimulation of gastric secretion and gastric and duodenal motor-evacuatory
      activity in patients with gastroesophageal reflux disease (GERD) associated with
      pathological refluxes, such as gastroesophageal reflux (GER) and
      duodenogastroesophageal reflux (DGER). SUBJECTS AND METHODS: The observational
      cross-sectional study was conducted to investigate and compare the parameters of
      intraesophageal and intragastric pH metry and peripheral
      electrogastroenterography in 103 GERD patients with endoscopically positive
      distal reflux esophagitis in GER and DGER. RESULTS: The patients with GERD
      developed pathological esophageal refluxes (both GER and DGER) in various degrees
      of impaired gastric production, from anacidity to hyperacidity. The patients with
      predominant DGER were found to have gastric hyperacidity and normal acidity
      slightly less frequently than those with predominant GER. The patients with GERD
      developing in the presence of predominant GER had moderate gastric stasis with
      discoordinated antroduodenal propulsion resulting from hypomotor dyskinesia of
      the stomach and duodenum. When DGER was predominant in the patients with GERD,
      the signs of gastric stasis and duodenal hyperkinesia were concurrent with
      discoordinated antroduodenal and duodenojejunal propulsion. CONCLUSION: The
      specific features of the esophagogastroduodenal secretory and motor evacuatory
      disorders found create conditions for the pathological refluxes into the
      esophagus, which differ in the composition of refluxate.

PMID- 27030179
TI  - [Specific features of gastroesophageal reflux disease associated with obesity and
      overweight].
AB  - AIM: To reveal the specific features of gastroesophageal reflux disease (GERD)
      associated with obesity and overweight, by investigating the clinical and
      endoscopic manifestations of the disease, 24-hour pH-metry scores, and leptin
      levels. SUBJECTS AND METHODS: A total of 131 patients with GERD were examined.
      The data about complaints and those from life and medical histories were
      collected; anthropometric measurements and the results of blood biochemical
      tests, esophagoduodenoscopy (EPDS), and pH-metry were assessed; and the serum
      levels of leptin and its receptor were estimated. The patients were allocated
      into a study group (104 obese and/or overweight patients) and a comparison one
      (27 normal weight people). RESULTS: Waist circumference, hip circumference, and
      blood glucose levels proved to be statistically significantly higher in the study
      group (p<0.00000, p<0.00002, and p<0.02, respectively). The obese patients were
      found to have a statistically significantly higher level of leptin and a lower
      level of its soluble receptors: the median leptin levels were 30.42 (13.42-45.62)
      ng/ml in the study group and 5.47 (3.35-7.68) ng/ml in the comparison group; the
      median levels of the receptors were 18.83 (14.98-25.11) ng/ml and 30.93 (24.68
      33.53) ng/ml, respectively). This group showed a moderate negative correlation
      between these indicators (rs=-0.451; p<0.0004). The study group displayed higher
      pH values in the gastric cardia and body (p<0.05 and p<0.04, respectively). The
      mucosal contact time with the refluxate having with a low pH value (<4) in the
      above segments turned out to be longer in the comparison group (p<0.05). There
      were weight-independent relationships of the leptin level to its spread,
      aggressiveness quotient, to the highest pH value in the gastric cardia and body,
      and to the mucosal contact time with the refluxate having a pH below 4.0
      (rs=0.543; p<0.006; rs=0.432; p<0.04; rs=0.431; p<0.04; rs=-0.450; p<0.03,
      respectively), leptin receptors with a pH ratio in the gastric cardia and body,
      to the number of reflux episodes longer than 5 minutes in the esophagus, and to
      the De Meester index for this indicator (rs=0.471; p<0.04; rs=-0.455; p<0.04; rs=
      0,454; p<0.04, respectively). CONCLUSION: Obese and overweight patients develop
      GERD in the presence of leptin resistance and biliary tract disease, which
      determines the specific features of the disease (alkaline or mixed refluxate) and
      the need for individualized therapy.

PMID- 27030180
TI  - [The frequency and clinical aspects of extraesophageal syndromes in elderly
      patients with gastroesophageal reflux disease].
AB  - AIM: To investigate the frequency of extraesophageal syndromes in elderly
      patients with gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: This
      cross-sectional study was conducted to compare the clinical manifestations of
      GERD in 1100 patients aged 60 to 75 years and in 453 patients aged 36 to 60
      years. A control group consisted of 154 elderly patients without GERD and 178
      mature-aged patients without this condition. GERD was diagnosed via analysis of
      its symptoms, esophagogastroduodenoscopy, and 24-hour pH monitoring on the basis
      of the Montreal consensus guidelines. Extraesophageal syndromes were detected
      actively using the current methods accepted to treat lung, heart, and ENT
      diseases and a simultaneous gastroesophageal examination. RESULTS: Chronic cough,
      asthma, chronic laryngitis, cardialgias and cardiac arrhythmias were much more
      common in elderly patients with GERD than in those without this condition and
      prevalent in patients with erosive esophagitis and Barrett's esophagus as
      compared with those with non-erosive reflux disease. The mature-aged patients
      were recorded to have similar but less pronounced trends. The authors proposed an
      algorithm for the management of patients with extraesophageal manifestations of
      GERD, the important aspect of which was two-month acid-suppressive therapy used
      as both diagnostic testing and empirical treatment for this pathology.
      CONCLUSION: The extraesophageal manifestations of GERD in elderly patients are a
      serious clinical problem calling for considerable attention.

PMID- 27030181
TI  - [European Registry on the management of Helicobacter pylori infection (Hp-EuReg
      protocol): The first results of Russian centers].
AB  - AIM: To assess the clinical practice of diagnosis and treatment in patients with
      Helicobacter pylori infection and to compare this practice with the international
      guidelines in the European Registry on the management of Helicobacter pylori
      infection, Hp-EuReg protocol), a multicenter prospective observational study
      initiated by the European Helicobacter and Microbiota Study Group. MATERIALs AND
      METHODS: The data of 813 patients infected with H. pylori and entered in the Hp
      EuReg register by the Russian centers in 2013-2015 were analyzed. RESULTS: The
      most common methods for the primary diagnosis of H. pylori infection are
      histology (40.3%), rapid urease test (35.7%), and serology (17.2%). The duration
      of H. pylori eradication therapy was 7, 10, and 14 days in 18.0, 49.3, and 25.1%,
      respectively. To monitor the effectiveness of treatment, the investigators used a
      histological examination (34%), a urea breath test (27.3%), H. pylori stool
      antigen (22.8%), and a rapid urease test (16.3%). A serological test was carried
      out in 2.5% of the cases. No monitoring was done in 13.5% of the patients. The
      average eradication efficiency was 82.6%. If the therapy was ineffective, 80% of
      physicians did not intend to prescribe a new cycle of treatment. CONCLUSION:
      Significant differences were found between clinical practice and the current
      guidelines.

PMID- 27030183
TI  - [Use of mesenchymal stem cells in the combination therapy of ulcerative colitis].
AB  - AIM: To compare results of treatment in patients with moderate and severe
      ulcerative colitis (UC), receiving standart anti-inflammatory therapy (second
      group) and its combination with bone marrow-derived mesenchymal stromal cells
      (MSC) (first group). RESULTS: Complex therapy of UC acute flare-up, including MSC
      did not influence on reccurence frequency, remission duration and mean value of
      clinical and endoscopic activity indices during 1 year of follow-up: in 1 group
      UC flare-up occurred in 2 (16.7%) patients, in 2 group--in 3 patients (30%). RR
      was 0.3 (95% CI 0/08--1.36; p=0.2; x2=1.47). After 2 years of follow-up risk of
      UC exacerbation in 1 group was 3 times lower than in the 2 group (p=0.03). Mean
      duration of remission in the 1 group was 22 months, in the 2 group--17 months
      (p=0.049). After 3 years of follow-up remission duration in the 1 and 2 groups
      were 22 and 22 months, respectively (p=0.66). Activity Index according to
      Rachmilevich in the 1 group was 4.75+/-1.13 points, in the 2--8.1+/-1.1 points
      (p=0.001). CONCLUSION: MSC application increases efficacy of anti-inflammatory
      treatment in patients with acute exacerbation of UC.

PMID- 27030182
TI  - [Celiac disease detection rate in gastroenterological patients].
AB  - AIM: To determine celiac disease detection rate in patients with digestive
      disease. SUBJECTS AND METHODS: A total of 318 gastroenterological patients
      admitted to be treated at the Central Research Institute of Gastroenterology in
      September to October 2012 were examined. The patients' age was 18 to 74 years
      (mean 51.5+/-16.4 years). Immunoglobulin A (IgA) and immunoglobulin G (IgG) anti
      gliadin antibodies (AGA), IgA anti-tissue transglutaminase (anti-tTG) antibodies
      and IgG anti-tTG antibodies were determined. When the antibodies were elevated,
      esophagogastroduodenoscopy with duodenal biopsy was performed. RESULTS: Forty-one
      of the 318 patients were found to have higher AGA (12.9%); out of them IgA AGA
      were in 17 (5.35%) patients and IgG AGA were also in 17 (5.35%). Elevated levels
      of both antibodies (IgA AGA and IgG AGA) were seen in 7 (2.2%) patients. Overall,
      the detection rate of increased AGA levels was 12.9%. The antibodies were more
      commonly higher in patients with liver diseases (21.8%) and in those with
      inflammatory bowel diseases (21.6%). Both IgA anti-tTG, IgG anti-tTG and IgA AGA,
      IgG AGA were detected in 6 (1.9%) of the 318 patients. The diagnosis of celiac
      disease was verified by duodenal histological examination in 3 (0.94%) of the 318
      patients. CONCLUSION: The celiac disease detection rate in gastroenterological
      patients was 0.94%.

PMID- 27030184
TI  - [A new non-invasive method for assessing steatosis in chronic liver diseases].
AB  - AIM: To assess the diagnostic accuracy of the controlled attenuation parameter
      (CAP) to determine the grade of hepatic steatosis (HS) in patients with chronic
      liver diseases (CLD) of different etiologies and to compare the obtained results
      with morphological findings. MATERIALS AND METHODS: A total of 45 patients (18
      men and 27 women) aged 25 to 73 years with CLD were examined. All the patients
      underwent liver puncture biopsy for assessing the HS index and fibrosis stage, as
      well as determination of hepatic elasticity (F, kPa) for estimating the stage of
      fibrosis and the grade of HS by CAP (S, dB/m) using a FibroScan device. When
      assessing HS, the CAP values of <229, 230-249, 250-276, and more than 277 dB/m
      correspond to HS grade 0 (S0), S1, S2, and S3, respectively. This is a pilot
      study in Russia. RESULTS: CAP is a rather high effective method in determining
      the absence of steatosis (S0) (the area under the receiver operating
      characteristics curve (AUROC) was 0.78) and severe steatosis (S3) (AUROC 0.90).
      AUROC was 0.64 and 0.59 for HS S1 and S2, which is regarded as satisfactory and
      poor RESULTS: respectively. Only 3 out of the 45 patients had HS, as evidenced by
      morphological examination; and the results of CAP showed another result; all the
      other cases had a HS grade corresponding to S1. In the entire cohort of the
      examinees, the sensitivity, specificity, and accuracy of CAP was 86, 69.5, and
      78%, respectively; AUROC was 0.77 (95% CI, 0.6587-0.9006; p=0.40). CONCLUSION:
      CAP is a promising method for the rapid and non-invasive diagnosis of HS in
      patients with CLD. At the same time, our findings show that it is necessary to
      clarify the quantitative indicators of the compliance of CAP and morphological
      evaluation of HS.

PMID- 27030185
TI  - [Evaluation of the efficiency of hepatoprotective monotherapy using succinic acid
      and methionine for nonalcoholic fatty liver disease at the stage of
      steatohepatitis].
AB  - AIM: To evaluate the efficiency of Remaxol monotherapy in patients with
      nonalcoholic fatty liver disease (NAFLD) at the stage of steatohepatitis (SH).
      MATERIALS AND METHODS: The treatment of 156 patients with NAFLD at the stage of
      SH was analyzed. A study group included 84 patients who had received intravenous
      Remaxol, 400 ml, dropwise at a rate of 40-60 drops per minute once daily in the
      morning for 10 days; a control group of 72 patients had been treated with the
      conventional scheme. RESULTS: During the treatment, the study group showed a
      rapider relief of the manifestations of asthenovegetative and dyspeptic syndromes
      and a reduction in the magnitude of biochemical manifestations of cytolytic and
      cholestatic syndromes than did the control group. CONCLUSION: Incorporation of
      Remaxol into the therapy regimen in patients with NAFLD at the stage of SH
      enhances the effectiveness of treatment.

PMID- 27030186
TI  - [Evaluation of cardiovascular remodeling and epicardial fat thickness in patients
      with chronic heart failure and metabolic syndrome].
AB  - AIM: To estimate cardiac chamber sizes and epicardial fat (EF) thickness in
      patients with chronic heart failure (CHF) and metabolic syndrome (MS). MATERIALS
      AND METHODS: The investigation enrolled 77 patients with CHF. The diagnosis of
      the latter was made on the basis of clinical symptoms and verified measuring N
      terminal pro-brain natriuretic peptide levels in all the patients. A study group
      (SG) included 39 patients with CHF and MS. A control group comprised 38 CHF
      patients without MS. Clinical and biochemical blood tests and electrocardiography
      were performed in all the patients. Cardiac chamber sizes, myocardial wall
      thickness, and EF were estimated from echocardiographic findings. Fatty liver
      index (FLI) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS)
      were calculated in all the patients. RESULTS: All the patients had clinical signs
      and symptoms of CHF. There were 25 (32%) men among the 77 patients. The mean age
      was 63.9+/-10.3 years. The patients with CHF and MS showed pronounced myocardial
      remodeling, which was manifested as significantly higher increases in the sizes
      of cardiac chambers and in the thickness of their walls and as larger EF
      thickness (EFT) and larger myocardial mass. In SG, EFT was 3.39+/-1.82 mm
      (p=0.00001). This group exhibited correlations between EFT and FLI (r=0.52;
      p=0.004), glycated hemoglobin levels (r=0.41; p=0.016), E peak (r=-0.25;
      p=0.005), E/A ratio (r=0.25; p=0.041), left ventricular (LV) end-systolic size
      (r=0.25; p=0.035), LV myocardial mass (r=0.29; p=0.038), NFS (r=0.29; p=0.002),
      and body mass index (r=0.29; p=0.003). CONCLUSION: The found correlations between
      EFT and the clinical and metabolic parameters of CHD and cardiovascular diseases
      allow EFT to be regarded as a new marker of risk for MS and cardiovascular
      diseases.

PMID- 27030187
TI  - [Duodenal dystrophy: An interdisciplinary problem].
AB  - Duodenal dystrophy (DD) is the pathological change in the wall of the duodenum,
      which is caused by chronic inflammation in its ectopic pancreatic tissue. The
      most common complications of DD are acute or chronic pancreatitis and impaired
      duodenal patency, which along with severe pain are an indication for surgical
      treatment. Pancreaticoduodenal resection is recognized as the operation of
      choice. The paper describes a clinical case demonstrating the efficiency and
      safety of minimally invasive (laparoscopic) surgical technologies in this
      category of patients. Resectional interventions of this volume are also shown to
      be accompanied by the development of pancreatic insufficiency that necessitates
      continuous enzyme replacement therapy. 

PMID- 27030188
TI  - [Seronegative celiac disease: A case report].
AB  - The paper describes a rare case of celiac disease in the absence of serum anti
      tissue transglutaminase (anti-tTG) antibodies. A 51-year-old patient has been
      suffering from diarrheas for 20 years. He has lost 15 kg gradually; weakness
      progressed; muscle cramps, leg edemas, and signs of dynamic pseudoobstruction
      appeared. Morphological examination revealed small intestinal mucosal (SIM)
      villous atrophy (Marsh IIIC stage). IgA anti-tTG and IgG anti-tTG antibodies were
      0.086 and 0.178, respectively. The patient was prescribed a gluten-free diet,
      water electrolyte solutions to correct metabolic disturbances, and prednisolone.
      During a control examination after 6 months, the patient had no complaints and
      gained 22 kg, and the SIM villus height was increased. The specific feature of
      the case is specific negative serological tests for celiac disease. 

PMID- 27030189
TI  - [Visceral leishmaniasis concurrent with splenic marginal zone B-cell lymphoma].
AB  - Splenic marginal zone B-cell lymphoma (SMZBCL) is a rare non-Hodgkin B-cell
      lymphoma that presents with morphologically mature lymphoid cells corresponding
      in their immunological characteristics to secondary follicular marginal zone
      lymphocytes. It is clinically characterized by splenomegaly, moderate
      lymphocytosis, usually focal bone marrow lesion, sometimes moderate of monoclonal
      immunoglobulin in the serum (generally IgM or IgG) and/or urea, and a relatively
      benign course. Leishmaniasis is a transmissible natural focal infectious endemic
      disease that has a great diversity of clinical manifestations. The authors
      describe Russia's first case of SMZBCL concurrent with visceral leishmaniasis in
      a 52-year-old female patient admitted to a hematology hospital with weakness,
      splenomegaly, and lymphadenopathy. The simultaneous detection of lymphoma and
      leishmaniasis in the same biopsy specimen is extremely rare. Visceral
      leishmaniasis should be borne in mind as an opportunistic infection in patients
      with malignancies, particularly in immunocompromised persons who live or have
      stayed in the endemic areas. 

PMID- 27030190
TI  - First detection of West Nile virus in domestic pigeon in Korea.
AB  - West Nile virus (WNV) is a mosquito-borne zoonotic pathogen that has spread
      throughout Europe and the United States. Recently, WNV spread to East and
      Southeast Asia, and great efforts have been made in South Korea to prevent the
      spread of WNV from neighboring countries. In this study, we diagnosed the first
      case of WNV in pigeons (Columba livia domestica) residing in cities using a
      competitive enzyme-linked immunosorbent assay and confirmed it with nested
      reverse transcription polymerase chain reaction analysis and sequencing. This is
      the first report to provide convincing evidence that WNV is present within South
      Korea.

PMID- 27030191
TI  - Learning, memory and exploratory similarities in genetically identical cloned
      dogs.
AB  - Somatic cell nuclear transfer allows generation of genetically identical animals
      using donor cells derived from animals with particular traits. To date, few
      studies have investigated whether or not these cloned dogs will show identical
      behavior patterns. To address this question, learning, memory and exploratory
      patterns were examined using six cloned dogs with identical nuclear genomes. The
      variance of total incorrect choice number in the Y-maze test among cloned dogs
      was significantly lower than that of the control dogs. There was also a
      significant decrease in variance in the level of exploratory activity in the open
      fields test compared to age-matched control dogs. These results indicate that
      cloned dogs show similar cognitive and exploratory patterns, suggesting that
      these behavioral phenotypes are related to the genotypes of the individuals.

PMID- 27030192
TI  - Development and evaluation of an immunochromatographic assay using a gp51
      monoclonal antibody for the detection of antibodies against the bovine leukemia
      virus.
AB  - Infection of cattle with bovine leukemia virus (BLV) has been observed and
      reported worldwide, including in Korea. The onsite identification of infected
      cattle would help decreasing and eradicating BLV infections on farms. Here, we
      present a new immunochromatographic assay that employs monoclonal antibodies
      (MAbs) for the detection of antibodies against BLV in the field. BLV envelope
      glycoprotein (gp)51 was expressed in E. coli, and MAbs against recombinant BLV
      gp51 were generated for the development of an immunochromatographic assay to
      detect BLV antibodies in cattle. The sensitivity and specificity of the assay
      were determined by comparing these results with those obtained from a standard
      enzyme linked immunosorbent assay (ELISA). A total of 160 bovine sera were used
      to evaluate the new immunochromatographic assay. Using ELISA as a reference
      standard, the relative specificity and sensitivity of this assay were determined
      to be 94.7% and 98%, respectively. Because of its high sensitivity and
      specificity, this BLV antibody detection assay would be suitable for the onsite
      identification of BLV infection in the field.

PMID- 27030193
TI  - Therapeutic effect of topical application of curcumin during treatment of
      radiation burns in a mini-pig model.
AB  - Curcumin protects the skin against radiation-induced epidermal damage and
      prevents morphological changes induced by irradiation skin, thereby maintaining
      the epidermal thickness and cell density of basal layers. In this study, the
      effects of topical curcumin treatment on radiation burns were evaluated in a mini
      pig model. Histological and clinical changes were observed five weeks after
      radiation exposure to the back (60Co gamma-radiation, 50 Gy). Curcumin was
      applied topically to irradiated skin (200 mg/cm2) twice a day for 35 days.
      Curcumin application decreased the epithelial desquamation after irradiation.
      Additionally, when compared to the vehicle-treated group, the curcumin-treated
      group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB.
      Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area,
      whereas curcumin treatment stimulated wound healing. These results suggest that
      curcumin can improve epithelial cell survival and recovery in the skin and
      therefore be used to treat radiation burns.

PMID- 27030194
TI  - Claudin-1, -2, -4, and -5: comparison of expression levels and distribution in
      equine tissues.
AB  - Claudins, which are known as transmembrane proteins play an essential role in
      tight junctions (TJs) to form physical barriers and regulate paracellular
      transportation. To understand equine diseases, it is helpful to measure the
      tissue-specific expression of TJs in horses. Major equine diseases such as colic
      and West Nile cause damage to TJs. In this study, the expression level and
      distribution of claudin-1, -2, -4, and -5 in eight tissues were assessed by
      Western blotting and immunohistochemistry methods. Claudin-1 was primarily
      identified in the lung, duodenum, and uterus, claudin-2 was evenly observed in
      equine tissues, claudin-4 was abundantly detected in the liver, kidney and
      uterus, and claudin-5 was strongly expressed in the lung, duodenum, ovary, and
      uterus, as determined by Western blotting method. The localization of equine
      claudins was observed by immunohistochemistry methods. These findings provide
      knowledge regarding the expression patterns and localization of equine claudins,
      as well as valuable information to understand tight junction-related diseases
      according to tissue specificity and function of claudins in horses.

PMID- 27030195
TI  - Prevalence of Salmonella enterica and Shiga toxin-producing Escherichia coli in
      zoo animals from Chile.
AB  - Salmonella (S.) enterica and Shiga toxin-producing Escherichia coli (STEC) are
      foodborne pathogens. Here, we report the prevalence of S. enterica and STEC in
      feces of 316 zoo animals belonging to 61 species from Chile. S. enterica and STEC
      strains were detected in 7.5% and 4.4% of animals, respectively. All Salmonella
      isolates corresponded to the serotype Enteritidis. To the best of our knowledge,
      this is the first report of S. Enteritidis in the culpeo fox (Lycalopex
      culpaeus), black-capped capuchin (Sapajus apella) and Peruvian pelican (Pelecanus
      thagus) and the first STEC report in Thomson's gazelle (Eudorcas thomsonii).

PMID- 27030196
TI  - Paclitaxel inhibits the hyper-activation of spleen cells by lipopolysaccharide
      and induces cell death.
AB  - Paclitaxel was isolated from the bark of the Pacific yew, Taxus brevifolia, and
      used as an anticancer agent. Paclitaxel prevents cancer cell division by
      inhibiting spindle fiber function, inducing cell death. A recent study
      demonstrated that paclitaxel binds to myeloid differentiation protein-2 of Toll
      like receptor 4 and prevents the signal transduction of lipopolysaccharide (LPS).
      Paclitaxel converts immune cells hypo-responsive to LPS. In this study, we
      investigated whether paclitaxel can inhibit the phenotype and function of immune
      cells. To accomplish this, we used spleen cells, a major type of immune cell,
      LPS, a representative inflammatory agent and a mitogen for B lymphocytes. LPS
      profoundly increased the activation and cytokine production of spleen cells.
      However, paclitaxel significantly inhibited LPS-induced hyper-activation of
      spleen cells. Furthermore, we found that paclitaxel induced cell death of LPS
      treated spleen cells. These results suggest that paclitaxel can inhibit the hyper
      immune response of LPS in spleen cells via a variety of mechanisms. These
      findings suggest that paclitaxel can be used as a modulating agent for diseases
      induced by hyper-activation of B lymphocytes. Taken together, these results
      demonstrate that paclitaxel inhibits the function of spleen cells activated by
      LPS, and further induces cell death.

PMID- 27030197
TI  - Improvement of pregnancy rate by intrauterine administration of dexamethasone and
      recombinant human leukemia inhibitory factor at the time of embryo transfer in
      cattle.
AB  - Bovine embryos (day 5) were cultured to day 10 with or without 100 ng/mL
      PGF2alpha in medium supplemented with control; 100 nM Dex; 1,000 U/mL recombinant
      human leukemia inhibitory factor (rhLIF); or Dex+rhLIF. Although the rates to
      development to the blastocyst were not significantly different among groups, the
      hatching rate after additional culture with Dex +/or rhLIF was significantly
      higher in all supplemented groups than the control (p < 0.05). In the presence of
      PGF2alpha, the hatching rate was significantly restored in all supplemented
      groups relative to the group treated with only PGF2alpha and the control (p <
      0.05). Embryo transfer (ET) was performed with blastocysts (day 7). PGF2alpha
      levels of control recipient cows were significantly higher in the circulatory
      blood samples collected 60 min after ET than in samples collected 60 min before
      ET (p < 0.005), and were decreased in cows injected with loading medium
      supplemented with Dex+rhLIF (p < 0.005). Pregnancy rate was significantly higher
      in the ET group that received supplemented embryo-loading medium than in the non
      supplemented control (p < 0.05). The intrauterine administration of Dex and rhLIF
      at ET prevented increased PGF2alpha in circulatory blood and resulted in enhanced
      pregnancy rate.

PMID- 27030198
TI  - Post-pandemic seroprevalence of human influenza viruses in domestic cats.
AB  - The continuous exposure of cats to diverse influenza viruses raises the concern
      of a potential role of cats in the epidemiology of these viruses. Our previous
      seroprevalence study of domestic cat sera collected during the 2009 H1N1 pandemic
      wave (September 2009-September 2010) revealed a high prevalence of pandemic H1N1,
      as well as seasonal H1N1 and H3N2 human flu virus infection (22.5%, 33.0%, and
      43.5%, respectively). In this study, we extended the serosurvey of influenza
      viruses in cat sera collected post-pandemic (June 2011-August 2012). A total of
      432 cat sera were tested using the hemagglutination inhibition assay. The results
      showed an increase in pandemic H1N1 prevalence (33.6%) and a significant
      reduction in both seasonal H1N1 and H3N2 prevalence (10.9% and 17.6%,
      respectively) compared to our previous survey conducted during the pandemic wave.
      The pandemic H1N1 prevalence in cats showed an irregular seasonality pattern in
      the post-pandemic phase. Pandemic H1N1 reactivity was more frequent among female
      cats than male cats. In contrast to our earlier finding, no significant
      association between clinical respiratory disease and influenza virus infection
      was observed. Our study highlights a high susceptibility among cats to human
      influenza virus infection that is correlated with influenza prevalence in the
      human population.

PMID- 27030199
TI  - Transgenesis for pig models.
AB  - Animal models, particularly pigs, have come to play an important role in
      translational biomedical research. There have been many pig models with
      genetically modifications via somatic cell nuclear transfer (SCNT). However,
      because most transgenic pigs have been produced by random integration to date,
      the necessity for more exact gene-mutated models using recombinase based
      conditional gene expression like mice has been raised. Currently, advanced genome
      editing technologies enable us to generate specific gene-deleted and -inserted
      pig models. In the future, the development of pig models with gene editing
      technologies could be a valuable resource for biomedical research. 

PMID- 27030200
TI  - Effects of gonadotropin-releasing hormone administration or a controlled internal
      drug-releasing insert after timed artificial insemination on pregnancy rates of
      dairy cows.
AB  - This study investigated the effects of gonadotrophin-releasing hormone (GnRH)
      administration (Experiment 1) and a controlled internal drug-releasing (CIDR)
      insert (Experiment 2) after timed artificial insemination (TAI) on the pregnancy
      rates of dairy cows. In Experiment 1, 569 dairy cows that underwent TAI (day 0)
      following short-term synchronization with prostaglandin F2alpha were randomly
      allocated into two groups: no further treatment (control, n = 307) or injection
      of 100 ug of gonadorelin on day 5 (GnRH, n = 262). In Experiment 2, 279 dairy
      cows that underwent TAI (day 0) following Ovsynch were randomly allocated into
      two groups: no further treatment (control, n = 140) or CIDR insert treatment from
      days 3.5 to 18 (CIDR, n = 139). The probability of pregnancy following TAI did
      not differ between the GnRH (34.4%) and control (31.6%, p > 0.05) groups.
      However, the probability of pregnancy following TAI was higher (odds ratio: 1.74,
      p < 0.05) in the CIDR group (51.1%) than in the control group (39.3%). Overall,
      CIDR insert treatment at days 3.5 to 18 increased pregnancy rates relative to non
      treated controls, whereas a single GnRH administration on day 5 did not affect
      the pregnancy outcomes of dairy cows.

PMID- 27030201
TI  - Effect of fermented soybean products intake on the overall immune safety and
      function in mice.
AB  - Various functional activities have been reported for the fermented soybean
      products doenjang (DJ) and cheonggukjang (CGJ), although no systemic
      investigations of their immune functions have been conducted to date. We examined
      the effects of an experimental diet of DJ, CGJ, or a mixture of unfermented raw
      material for 4 weeks on overall immunity and immune safety in mice. No
      significant alterations were observed in peripheral or splenic immune cells among
      groups. Enhanced splenic natural killer cell activity was observed in the DJ and
      CGJ groups compared with the plain diet group. T helper type-1 (Th1)-mediated
      immune responses were enhanced in the DJ and CGJ groups with an upregulated
      production ratio of IFN-gamma vs. IL-4 and IgG2a vs. IgG1 in stimulated splenic T
      and B cells, respectively. Resistance to Listeria monocytogenes infection was
      observed in the DJ and CGJ groups. Overall, the results of this study suggest
      that DJ and CGJ intake consolidates humoral and cellular immunity to Th1
      responses.

PMID- 27030202
TI  - Isolation of lactobacillus reuteri from Peyer's patches and their effects on sIgA
      production and gut microbiota diversity.
AB  - SCOPE: We previously reported that specific Lactobacillus reuteri colonized
      within mouse Peyer's patches (PP) effectively prevented high fat diet induced
      obesity and low-grade chronic inflammation. We further investigated the role of
      PP Lactobacillus reuteri on sIgA production in rats in this study. METHODS AND
      RESULTS: Lactobacilli were isolated from rat PP. All isolates were L. reuteri and
      belonged to three phenotypes according to amplified fragment length polymorphism
      analysis. Typical strains of two main clusters, PP1 and PP2, were used to treat
      control and vitamin A deficient (VAD) rats, respectively. The feeding of PP1 and
      PP2 affected sIgA and Lactobacillus diversity by strain-specific manner. Free
      sIgA was significantly increased by PP1 (p = 0.069) and PP2 (p < 0.05) in the
      control rats but not in the VAD rats. Only PP1 significantly changed PP
      Lactobacillus diversity in the control rats (p < 0.05). However, PP2 specifically
      changed ileal Lactobacillus diversity in both control and VAD rats. Fecal sIgA
      was correlated with PP Lactobacillus diversity (R(2) = 0.7958, p = 0.011).
      CONCLUSION: Modulation of sIgA production by PP L. reuteri of rat is dependent on
      vitamin A and change of Lactobacillus diversity in PP.

PMID- 27030203
TI  - Impact of aggregating exposure information from cases and controls when building
      a population-based job-exposure matrix from past expert evaluations.
AB  - OBJECTIVES: To assess whether the inclusion of data from cases would bias a job
      exposure matrix (JEM), we evaluated whether exposures were systematically
      different between cases and controls from a large historical case-control study.
      METHODS: Data included 10 381 jobs assessed for occupational exposure to 294
      agents within a lung cancer case-control study. For each sex, 1 JEM was developed
      from case jobs, and 1 from control jobs: with occupation (four-digit occupational
      codes), time period (1945-1959, 1960-1984, 1985-1995) and agent axes. We
      estimated concordance in exposure status (defined as probability of exposure
      threshold >=5%) and exposure metrics of probability and intensity of exposure,
      between the 2 JEMs. RESULTS: Of all hypothetical occupation-period-agent
      combinations, most had no or few observations. Among males there were 8136 common
      cells (24-occupational codes, 3-periods, 226-agents), containing sufficient
      observations for comparison with 92% concordance in exposure status; discordance
      was equally likely to be towards cases or controls. Females had 1710 common cells
      (9-occupational codes, 3-periods, 114-agents) with 93% concordance in exposure
      status; discordant cells were more likely to reflect greater exposure among
      cases. Among concordantly exposed cells, probability and intensity of exposures
      were highly correlated between the case JEM and control JEM (Kendall tau>0.50),
      and absolute differences were small (median difference in probability <1.5%,
      median ratio in intensity=1.00) for both sexes. CONCLUSIONS: Agreement between
      the case JEM and control JEM was high, suggesting that aggregating the case and
      control information in our study into a single JEM is justifiable given the
      benefits of increased sample size.

PMID- 27030204
TI  - Exposure-response relationships between movements and postures of the wrist and
      carpal tunnel syndrome among male and female house painters: a retrospective
      cohort study.
AB  - OBJECTIVES: To investigate exposure-response relationships between measured
      movements and postures of the wrist and the incidence of carpal tunnel syndrome
      (CTS), and any modifications by sex. METHODS: In 2011, we established a
      historical cohort of 9364 members of the Painters' Union in Denmark. Self
      reported task distributions were obtained by questionnaire (53% responded) and
      combined with sex-specific task exposure matrices to get individual estimates of
      exposure intensity, that is, velocity of wrist flexion/extension, mean power
      frequency (MPF) and non-neutral wrist postures. Exposure duration was assessed
      from yearly working proportions. Registered first-time hospital discharge CTS
      diagnoses and CTS surgery were collected as outcomes. The cohort was followed
      from 1994 to 2010. Log-linear Poisson regression was used. RESULTS: For CTS
      diagnoses, the adjusted incidence rate ratios (IRRs) increased with increasing
      wrist velocity (IRR=1.37 (95% CI 1.10 to 1.71) per  degrees /s) and MPF (IRR=1.53
      (95% CI 1.21 to 1.91) per 0.01 Hz). For CTS surgery, the results were similar.
      The outcomes were not related to non-neutral postures or exposure duration. The
      adjusted IRRs for women were higher than those for men. There were no
      multiplicative interaction effects between exposure intensity, exposure duration
      and sex. However, the absolute incidence rates (IRs) increased at a steeper rate
      for women than for men, indicating an additive interaction. CONCLUSIONS: The
      incidence of CTS increased with increasing velocity of wrist flexion/extension
      and MPF of wrist movements. The relative increase in incidence rates was the same
      for women and men, but the absolute incidence rates increased at a steeper rate
      for women than for men.

PMID- 27030205
TI  - Leukaemic blast cannibalism in acute megakaryoblastic leukaemia with myeloid
      sarcoma.

PMID- 27030206
TI  - In-situ Observation of Size and Irradiation Effects on Thermoelectric Properties
      of Bi-Sb-Te Nanowire in FIB Trimming.
AB  - In this report, the thermoelectric properties of a Bi0.8Sb1.2Te2.9 nanowire (NW)
      were in-situ studied as it was trimmed from 750 down to 490 and 285 nm in
      diameter by a focused ion beam. While electrical and thermal conductivities both
      indubitably decrease with the diameter reduction, the two physical properties
      clearly exhibit different diameter dependent behaviors. For 750 and 490 nm NWs,
      much lower thermal conductivities (0.72 and 0.69 W/m-K respectively) were
      observed as compared with the theoretical prediction of Callaway model. The
      consequence indicates that in addition to the size effect, extra phonon
      scattering of defects created by Ga ion irradiation was attributed to the
      reduction of thermal conductivities. As the NW was further trimmed down to 285
      nm, both the electrical and thermal conductivities exhibited a dramatic reduction
      which was ascribed to the formation of amorphous structure due to Ga ion
      irradiation. The size dependence of Seebeck coefficient and figure of merit (ZT)
      show the maximum at 750 nm, then decrease linearly with size decrease. The study
      not only provides the thoroughly understanding of the size and defect effects on
      the thermoelectric properties but also proposes a possible method to manipulate
      the thermal conductivity of NWs via ion irradiation. 

PMID- 27030208
TI  - Safety assessment of selected medicinal food plants used in Ayurveda through
      CYP450 enzyme inhibition study.
AB  - BACKGROUND: Andrographis paniculata, Bacopa monnieri and Centella asiatica are
      mentioned in Ayurveda for the management of neurodegenerative disorders. These
      plants and their phytomolecules, such as andrographolide, bacoside A and
      asiaticoside, were studied for their inhibition potential on pooled CYP450 as
      well as human CYP3A4, CYP2D6, CYP2C9 and CYP1A2 by CYP-CO complex assay and
      fluorogenic assay respectively followed by IC50 determination. Quantification of
      bioactive compounds present in the extracts was done by RP-HPLC. Heavy metal
      content in the selected medicinal plants was determined by atomic absorption
      spectroscopy. RESULT: CYP-CO complex assay indicated significantly less
      inhibition potential than standard inhibitor (P < 0.05 and above). A. paniculata
      showed highest inhibitory activity against CYP3A4 and CYP2D6 (IC50 = 63.06 +/-
      1.35 ug mL-1 ; 88.80 +/- 3.32 ug mL-1 ), whereas C. asiatica and B. monnieri
      showed least inhibitory activity against CYP1A2 (IC50 = 288.83 +/- 1.61 ug mL-1 )
      and CYP2C9 (184.68 +/- 3.79 ug mL-1 ), respectively. In all cases the extract
      showed higher inhibition than the single bioactive compounds. The heavy metals
      content in the plant extracts were within the permissible limits. CONCLUSION: The
      findings suggested that selected food plants and bioactive compounds contributed
      negligible interaction potential with CYP isozymes and may not possess any
      harmful effect with regard to their therapeutic application. (c) 2016 Society of
      Chemical Industry.

PMID- 27030209
TI  - Quantum-Classical Nonadiabatic Dynamics: Coupled- vs Independent-Trajectory
      Methods.
AB  - Trajectory-based mixed quantum-classical approaches to coupled electron-nuclear
      dynamics suffer from well-studied problems such as the lack of (or incorrect
      account for) decoherence in the trajectory surface hopping method and the
      inability of reproducing the spatial splitting of a nuclear wave packet in
      Ehrenfest-like dynamics. In the context of electronic nonadiabatic processes,
      these problems can result in wrong predictions for quantum populations and in
      unphysical outcomes for the nuclear dynamics. In this paper, we propose a
      solution to these issues by approximating the coupled electronic and nuclear
      equations within the framework of the exact factorization of the electron-nuclear
      wave function. We present a simple quantum-classical scheme based on coupled
      classical trajectories and test it against the full quantum mechanical solution
      from wave packet dynamics for some model situations which represent particularly
      challenging problems for the above-mentioned traditional methods. 

PMID- 27030207
TI  - Involvement of Rab6a in organelle rearrangement and cytoskeletal organization
      during mouse oocyte maturation.
AB  - Rab GTPases have been reported to define the identity and transport routes of
      vesicles. Rab6 is one of the most extensively studied Rab proteins involved in
      regulating organelle trafficking and integrity maintenance. However, to date, the
      function of Rab6 in mammalian oocytes has not been addressed. Here we report
      severe disorganization of endoplasmic reticulum upon specific knockdown of Rab6a
      in mouse oocytes. In line with this finding, intracellular Ca(2+) stores are
      accordingly reduced in Rab6a-depleted oocytes. Furthermore, in these oocytes, we
      observe the absence of cortical granule free domain, which is a kind of special
      organelle in matured oocytes and its exocytosis is calcium dependent. On the
      other hand, following Rab6a knockdown, the prominent defects of cytoskeletal
      structures are detected during oocyte meiosis. In particular, the majority of
      Rab6a-depleted oocytes fail to form the actin cap, and the frequency of spindle
      defects and chromosome misalignment is significantly elevated. In summary, our
      data reveal that Rab6a not only participates in modulating the organization of
      oocyte organelles, but also is a novel regulator of meiotic apparatus in
      mammalian oocytes. 

PMID- 27030210
TI  - A Systematic Review Protocol to Assess the Effects of Physical Activity on Health
      and Quality of Life Outcomes in Adolescent Cancer Survivors.
AB  - BACKGROUND: The benefits of physical activity for child and adult cancer
      survivors have been summarized in previous systematic reviews. However, no review
      has summarized the evidence for adolescent cancer survivors. OBJECTIVE: This
      paper describes the design of a protocol to conduct a systematic review of
      published studies examining the effects of physical activity on health and
      quality of life outcomes for adolescent cancer survivors. METHODS: Several
      guidelines informed the development of this protocol. The Preferred Reporting
      Items for Systematic Review and Meta-Analysis Protocols guidelines provided the
      structure by which to conduct and report the protocol; though some adaptations
      were made with regards to search terms, data synthesis, and evaluating the risk
      of bias. The Cochrane Handbook for Systematic Reviews of Interventions was used
      to guide research question development, search term selection, and the data
      extraction form. The Consolidated Standards of Reporting Trials guidelines helped
      inform the data extraction form. Lastly, the Guidance on the Conduct of Narrative
      Synthesis in Systematic Reviews informed the data synthesis. Ten electronic
      databases were identified and a search strategy was developed using a combination
      of Medical Subject Headings terms and keywords that were developed by the authors
      and peer reviewed by a university librarian. Both authors independently screened
      eligible studies for final inclusion, and data were abstracted using a form
      developed by the research team. A decision was made to synthesize all data
      narratively. RESULTS: The review has now been completed, peer-reviewed, and
      accepted for publication in a forthcoming issue of JMIR Cancer. CONCLUSIONS: As
      this will be the first systematic review on this topic, outlining the protocol
      ensures transparency for the completed review. Further, this protocol illustrates
      how elements from several guidelines were incorporated to answer the research
      question (ie, what is the effect of physical activity on health and quality of
      life outcomes in adolescent cancer survivors). This flexible approach was
      necessary as a function of the paucity of available research on this topic.

PMID- 27030212
TI  - Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts
      showed BACH1-Pparg pathway in adipogenesis.
AB  - The transcription repressor BTB and CNC homology 1 (BACH1) represses genes
      involved in heme metabolism and oxidative stress response. BACH1 also suppresses
      the p53-dependent cellar senescence in primary mouse embryonic fibroblasts
      (MEFs). To investigate the role of BACH1 in MEF other than its known functions,
      we carried out a genomewide mapping of binding site for BACH1 and its heterodimer
      partner MAFK in immortalized MEFs (iMEFs) using chromatin immunoprecipitation and
      next-generation sequencing technology (ChIP-sequence). The comparative analysis
      of the ChIP-sequence data and DNA microarray data from Bach1-deficient and wild
      type (WT) iMEF showed 35 novel candidate target genes of BACH1. Among these
      genes, five genes (Pparg, Nfia, Ptplad2, Adcy1 and Ror1) were related with lipid
      metabolism. Bach1-deficient iMEFs showed increased expression of mRNA and protein
      of PPARgamma, which is the key factor of adipogenesis. These cells also showed a
      concomitant increase in ligand-dependent activation of PPARgamma target genes
      compared with wild-type iMEFs. Moreover, Bach1-deficient iMEFs efficiently
      differentiated to adipocyte compared with wild-type cells in the presence of
      PPARgamma ligands. Our results suggest that BACH1 regulates expression of
      adipocyte-related genes including Pparg and potentiates adipocyte differentiation
      capacity. 

PMID- 27030213
TI  - Child Psychological Maltreatment and Its Correlated Factors in Chinese Families.
AB  - The present study aimed to explore the prevalence and frequency of child
      psychological maltreatment and its correlated factors in Chinese families. A
      cross-sectional investigation was conducted among 1,002 parents of primary school
      students in Yuncheng City, China. Data were collected using the self-report
      questionnaire anonymously. Results showed that 696 (69.5%) surveyed parents had
      different extents of psychological maltreatment toward their children in the past
      3 months. The high prevalence of parental psychology maltreatment was
      significantly associated with high scores on parental over-reactivity and low
      scores on recognition of child psychology maltreatment. These findings indicate
      that it is urgent to develop cultural interventions to raise parents' awareness
      of preventing child psychological maltreatment and to help parents use nonviolent
      child rearing in China. 

PMID- 27030211
TI  - Zyxin-Siah2-Lats2 axis mediates cooperation between Hippo and TGF-beta signalling
      pathways.
AB  - The evolutionarily conserved Hippo pathway is a regulator that controls organ
      size, cell growth and tissue homeostasis. Upstream signals of the Hippo pathway
      have been widely studied, but how microenvironmental factors coordinately
      regulate this pathway remains unclear. In this study, we identify LIM domain
      protein Zyxin, as a scaffold protein, that in response to hypoxia and TGF-beta
      stimuli, forms a ternary complex with Lats2 and Siah2 and stabilizes their
      interaction. This interaction facilitates Lats2 ubiquitination and degradation,
      Yap dephosphorylation and subsequently activation. We show that Zyxin is required
      for TGF-beta and hypoxia-induced Lats2 downregulation and deactivation of Hippo
      signalling in MDA-MB-231 cells. Depletion of Zyxin impairs the capability of cell
      migration, proliferation and tumourigenesis in a xenograft model. Zyxin is
      upregulated in human breast cancer and positively correlates with histological
      stages and metastasis. Our study demonstrates that Zyxin-Lats2-Siah2 axis may
      serve as a potential therapeutic target in cancer treatment. 

PMID- 27030214
TI  - Embelin Inhibits Invasion and Migration of MDA-MB-231 Breast Cancer Cells by
      Suppression of CXC Chemokine Receptor 4, Matrix Metalloproteinases-9/2, and
      Epithelial-Mesenchymal Transition.
AB  - Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant.
      Recent scientific evidence shows that EB induces apoptosis and inhibits migration
      and invasion in highly metastatic human breast cancer cells. However, the exact
      mechanisms of EB in tumor metastasis and invasion have not been fully elucidated.
      Here, we investigated the underlying mechanisms of antimetastatic activities of
      EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4)
      as well as matrix metalloproteinase (MMP)-9/2 expression and upregulated the
      tissue inhibitor of metalloproteinase 1 expression in MDA-MB-231 cells under
      noncytotoxic concentrations but not in MCF-7 cells. Additionally, EB inhibited
      the CXC motif chemokine ligand 12 induced invasion and migration activities of
      MDA-MB-231 cells. A detailed study of underlying mechanisms revealed that the
      regulation of the downregulation of CXCR4 was at the transcriptional level, as
      indicated by the downregulation of mRNA expression and suppression of nuclear
      factor-kappa B (NF-kappaB) activation. It further reduced the binding of NF
      kappaB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker
      proteins (neural cadherin and vimentin) and concurrently upregulated epithelial
      markers (epithelial cadherin and occludin). Overall, these findings suggest that
      EB can abrogate breast cancer cell invasion and metastasis by suppression of
      CXCR4, MMP-9/2 expressions, and inhibition of epithelial-mesenchymal transition
      and thus may have a great potential to suppress metastasis of breast cancer.
      Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27030215
TI  - Termination of seizure clusters is related to the duration of focal seizures.
AB  - OBJECTIVE: Clustered seizures are characterized by shorter than usual
      interseizure intervals and pose increased morbidity risk. This study examines the
      characteristics of seizures that cluster, with special attention to the final
      seizure in a cluster. METHODS: This is a retrospective analysis of long-term
      inpatient monitoring data from the EPILEPSIAE project. Patients underwent
      presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the
      occurrence of at least two consecutive seizures with interseizure intervals of <4
      h. Other definitions of seizure clustering were examined in a sensitivity
      analysis. Seizures were classified into three contextually defined groups:
      isolated seizures (not meeting clustering criteria), terminal seizure (last
      seizure in a cluster), and intracluster seizures (any other seizures within a
      cluster). Seizure characteristics were compared among the three groups in terms
      of duration, type (focal seizures remaining restricted to one hemisphere vs.
      evolving bilaterally), seizure origin, and localization concordance among pairs
      of consecutive seizures. RESULTS: Among 92 subjects, 77 (83%) had at least one
      seizure cluster. The intracluster seizures were significantly shorter than the
      last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster
      resembled the isolated seizures in terms of duration. Although focal only
      (unilateral), seizures were shorter than seizures that evolved bilaterally and
      there was no correlation between the seizure type and the seizure position in
      relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more
      likely to cluster compared with other localizations (p = 0.009). Seizure pairs
      that are part of a cluster were more likely to have a concordant origin than were
      isolated seizures. Results were similar for the 2 h definition of clustering, but
      not for the 8 h definition of clustering. SIGNIFICANCE: We demonstrated that
      intracluster seizures are short relative to isolated seizures and terminal
      seizures. Frontal and temporal lobe seizures are more likely to cluster.

PMID- 27030216
TI  - Three-dimensional splitting microfluidics.
AB  - Microfluidic systems with splitting structures are excellent for increasing
      emulsion production. However, traditional two-dimensional (2D) lithographic
      systems require complex modification of the microchannel surfaces and achieve
      only 2D splitting of the droplets. Herein, we present new glass capillary
      microfluidic devices that perform three-dimensional (3D) splitting of droplets.
      These devices are simply constructed using different structural glass capillaries
      as the collection microchannels of the droplet microfluidic systems. We
      demonstrate that the devices are able to produce a 3D split of both single
      emulsions and double emulsions into two and three portions, respectively. These
      emulsions, after the splitting process, still have high monodispersity. We
      believe that this new technique for 3D splitting could be widely used, not only
      in the field of microfluidics but also in chemical/biological applications (e.g.,
      drug delivery, micro-dispersion, etc.). 

PMID- 27030219
TI  - [Italy of miracles. Does the renaissaince of Italian science pass by the
      Vatican?].
AB  - In a commentary published in The Lancet on January 2016, Giuseppe Remuzzi and
      Richard Horton, analyse the origin of the decline of the Italian primacy in
      biomedical science. Among the others, the existence of Italian political groups
      "which oppose science simply to please the Church and to achieve political gain"
      was considered as detrimental for advancing research in such areas as assisted
      reproduction or embryonic stem cell research. Some hope for a change is raised,
      in the opinion of Remuzzi and Horton, by the more open attitude toward science of
      pope Francis. Hence, the two authors conclude that the time has come to promote a
      dialogue between Italian scientists and the Vatican and, by that, to see "if
      conditions are ripe to create a renaissance in Italian intellectual life". I
      humbly challange the analyses and conclusions of Remuzzi and Horton on the
      Italian scientific decline and the possible way forward. The rooth of the Italian
      decline in science are deep-seated into the chronic lack of resources, into the
      under-development of academic institutions, and into the lack of motivations for
      young researchers. As for bioethical paradigms, they are the end result of a co
      production between social norms and scientific development, and their definition
      would ideally involve the participation of large sectors of the society. One
      example of such a process is offered by the "Les Etats generaux de la bioethique"
      in France in 2009. The ethical discussion concerning biotech innovations is not
      limited to theological issues, but involves social aspects such as public health
      priorities, equity, and information strategies to avoid creating unrealistic
      expectations. 

PMID- 27030220
TI  - [Patients' increasing role in healthcare].
AB  - Since the late '90s citizens have been increasingly involved in healthcare,
      thanks to a shift in access to healthcare information, greater patients' and
      citizens' awareness about their rights and needs, and a change in physicians'
      attitudes and behavior. At the same time, to ensure the sustainability of the
      national health services, patients' needs are increasingly being examined in
      relation to the services and interventions needed, and to foster informed demand
      by patients and citizens, and appropriate prescriptions by physicians. Nowadays,
      patients already have a section in an authoritative medical journal. Working with
      clinicians, they set research priorities and the outcomes to be studied.
      Especially in UK and USA, they are invited to participate in the design and
      development of trials and in deciding which trials should be funded. The
      situation varies widely in different countries, though involving citizens in
      healthcare decisions is a common mantra. Even when they consult a clinician, the
      patients' role has evolved. People ask for information more often and want an
      active part in decisions about their health. Physicians start to pay more
      attention to the person and the social context, feelings and emotions, and person
      centered care has become a reference in the doctor-patient relationship. This
      article offers an overview of the changing roles of patients and citizens in
      healthcare. 

PMID- 27030221
TI  - [Looking for evidence-based medical informatics].
AB  - e-Health is experiencing a difficult time. On the one side, the forecast is for a
      bright digital health future created by precision medicine and smart devices. On
      the other hand, most large scale e-health projects struggle to make a difference
      and are often controversial. Both futures fail because they are not evidence
      based. Medical informatics should follow the example of evidence-based medicine,
      i.e. conduct rigorous research that gives us evidence to solve real world
      problems, synthesise that evidence and then apply it strictly. We already have
      the tools for creating a different universe. What we need is evidence, will, a
      culture of learning, and hard work. 

PMID- 27030222
TI  - [Forgoing treatments: a kind of euthanasia? A scientific approach to the debate
      about end of life decisions].
AB  - In the last decade an extensive debate on the topic of end of life decisions has
      developed in western countries, obtaining a worldwide media relevance.
      Philosophers, theologians, legal experts and doctors, focus their attention on
      the three thorny issues of the topic: forgoing treatments, euthanasia and
      assisted suicide. A thorough and respectful discussion on these issues should
      include all stakeholders - above all palliative care physicians - and should be
      encouraged in order to understand the views in favor or against the three
      practices, checking the different moral positions, and analyzing the cultural,
      social and legal aspects in the background on one hand, and, on the other, their
      impact on the health care systems. At present, in the fields of communications
      and politics, the debate related to the topic of these end of life practices is
      characterized by a confusion of terms and meanings. As an outcome, the term
      "euthanasia" is misused as a "container" including forgoing treatments,
      euthanasia and assisted suicide, while palliative sedation is wrongly considered
      as a procedure to cause death. This confusing approach does not permit to
      understand the real issues at the stake, keeping the debate at the tabloid level.
      Conversely, sharing the precise meaning of the words is the only way to provide
      tools to make rational, autonomous and responsible decisions, allowing individual
      informed choices in compliance with the principle of autonomy. This article is
      not aimed to take a moral stand in favor or against forgoing treatments,
      euthanasia and assisted suicide. Through an analysis based on scientific
      criteria, the authors firstly review the definitions of these three practices,
      examining the concepts enclosed in each term; secondly, they offer a glance on
      the legal approach to end of life issues in western countries; lastly, they
      investigate the relationship between these practices and palliative care culture
      in light of the medical societies official statements. The authors chosen to
      examine the topic of forgoing treatments, euthanasia and assisted suicide from a
      scientific point of view, because the clinical approach, taking into account the
      biological context of disease related to the human and social domains, seems to
      be able to better gather all the aspects of end of life practices, providing
      useful information to deal with them also in a philosophical or juridical
      perspective. 

PMID- 27030223
TI  - [Primary pleuropulmonary involvment in Waldenstrom's macroglobulinemia: an
      interdisciplinary issue].
AB  - The incidence of pleuropulmonary manifestations in Waldenstrom's
      macroglobulinemia is low in haematological as well as pneumological international
      literature. The progressive decrease concerning these manifestations is due
      essentially to scant interdisciplinary attention for new issues correlated with
      this specific involvement, that is poorly understood and rarely object of
      dedicated publications. 

PMID- 27030224
TI  - [Indications and future perspectives in the pharmacological treatment of
      hypercortisolism].
AB  - The hypercortisolism is a rare endocrine disease characterized by an autonomous
      steroid secretion or excessive adrenal stimulation by ACTH. the Surgical removal
      of the lesion directly responsible hypercortisolism represents the treatment of
      choice. When neurosurgery for pituitary adenoma is contraindicated, radiotherapy
      is candidate as the second line of therapy. Currently, the recent advances in
      medical therapy provide a viable alternative to surgery and radiotherapy, when
      these are not feasible or followed by relapses (present in more than one third of
      cases) of the underlying disease. Recently, also in Italy, are available
      pharmacological agents with central activity (pasireotide) specifically indicated
      for treating Cushing's disease together with peripherally acting drugs
      (metyrapone and ketoconazole) that are used in a broader spectrum of
      hypercortisolemic clinical pictures. In addition, drugs active in the inhibition
      of steroidogenesis provide a valid support to the patient's surgical preparation
      allowing the reduction or normalization of plasma cortisol levels. 

PMID- 27030225
TI  - [A qualitative content analysis of HIV consultation: when conversation is about
      aother than disease].
AB  - INTRODUCTION: In recent decades the literature has paid growing attention to the
      communicative and relational aspects of the medical consultation, showing a
      consistent presence - besides contents related to the disease and the patient's
      agenda - of friendly conversations or "chitchat", i.e. interventions related to
      social, relational and personal aspects made by the physician or by the patient.
      The aim of the study is to analyze the content, frequency and who between the
      doctor and the patient introduce the "chitchat" during the check-up visits with
      HIV+ patients and assess the patient satisfaction at the end of the visit.
      METHODS: 52 visits at the clinic of Infectious Diseases in a hospital in Northern
      Italy were videotaped and transcribed. All patients filled out a satisfaction
      questionnaire at the end of the visit. The friendly conversations were
      extrapolated, and analyzed qualitatively with a content thematic analysis, and
      quantitatively using descriptive statistics. RESULTS: The following thematic
      areas were identified: patient's medical issue not related to HIV; medical
      condition of a family member or others; labour issues of the patient; patient's
      relational/emotional issues; relational/working issues work of others; social
      conversations; physician's self-disclosure. "Chitchat" accounted for 26.5% of the
      time of the visit and in 63% of cases was introduced by doctors. The 91.4% of the
      patients was highly satisfied. CONCLUSIONS: The presence of friendly
      conversations during the doctor-patient exchanges in the field of HIV infection
      seems to have a role of consolidation of the therapeutic relationship and seems
      to reflect an authentic interest of the physician towards the patient as a
      person.

PMID- 27030227
TI  - [Not Available].

PMID- 27030226
TI  - [Not Available].

PMID- 27030228
TI  - [Not Available].

PMID- 27030229
TI  - Isolated Talonavicular Arthrodesis.

PMID- 27030230
TI  - Clinical Outcome and Fusion Rate Following Simultaneous Subtalar Fusion and Total
      Ankle Arthroplasty.
AB  - BACKGROUND: Patients with arthritis or severe dysfunction involving both the
      ankle and subtalar joints can benefit from tibiotalocalcaneal (TTC) arthrodesis
      or total ankle replacement and subtalar fusion. TTC fusion is considered by many
      as a salvage operation resulting in a stiff ankle and hindfoot, considerably
      limiting global foot function. With the evolution of prosthetic design and
      operative techniques, total ankle replacement (TAR) has become a reasonable
      alternative to arthrodesis. The aim of this study was to investigate the fusion
      rate of the subtalar joint in patients simultaneously treated with total ankle
      replacement (TAR) and subtalar joint fusion. METHODS: This study included 25
      patients who underwent primary TAR and simultaneous subtalar fusion between May
      2011 and November 2014. Sixteen males (64%) and 9 females (36%) were enrolled
      with a mean age of 58 years (25-82). Patients were clinically assessed
      preoperatively and at 6 and 12 months postoperatively. Total follow-up time was
      24.2 +/- 11.6 months. Radiographic examination included a postoperative computed
      tomographic (CT) scan obtained 12 months after surgery. Three surgeons
      independently reviewed the CT scans and interobserver reliability was calculated.
      Functional scores were also assessed. RESULTS: At 12 months postoperatively, the
      subtalar fusion rate in patients treated with TAR and simultaneous subtalar
      fusion was 92%. There was a statistically significant increase in American
      Orthopaedic Foot & Ankle Society ankle/hindfoot score from 27.9 to 75.1. Ankle
      range of motion significantly increased from 12 to 32.8 degrees. Additionally,
      there was a statistically significant decrease in visual analog scale pain score
      from 8.6 to 2.1. CONCLUSIONS: TAR and simultaneous subtalar joint fusion were
      reliable procedures for the treatment of ankle and subtalar joint arthritis.
      Furthermore, CT scans showed an excellent reliability among orthopedic surgeons
      in determining the degree of successful fusion of subtalar arthrodesis. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 27030231
TI  - Secondary Arthrodesis After Total Ankle Arthroplasty.
AB  - BACKGROUND: While it is thought that stresses through the subtalar and
      talonavicular joints will be decreased after total ankle replacement (TAR)
      relative to ankle fusion, progressive arthritis or deformity of these joints may
      require a fusion after a successful TAR. However, after ankle replacement, it is
      unknown how hindfoot biomechanics and blood supply may be affected. Consequently,
      subsequent hindfoot joint fusion may be adversely affected. METHODS: We
      retrospectively identified a consecutive series of 1001 primary TARs performed
      between January 1998 and December 2014. We identified patients who underwent a
      secondary triple, subtalar or talonavicular arthrodesis to treat progressive
      arthritis or pes planus deformity. Clinical outcomes including pain and
      functional outcome scores, revision procedures, delayed union, nonunion,
      complications, and failure rates were recorded. Twenty-six patients (2.6%)
      required a subtalar (18), talonavicular (3), talonavicular and subtalar (3), or
      triple arthrodesis (2). Of these patients, 14 (54%) were males with an average
      age of 63.2 years and a mean 70.9 months follow-up. We then compared these
      patients to 13 patients who had a subtalar fusion after an ankle arthrodesis.
      RESULTS: The most common type of fixation used was 2 variable-pitch screws across
      each joint. Fresh-frozen allograft cancellous chips were the most common
      supplement to the fusion construct (80.8%). The mean time between TAR and
      secondary fusion procedure was 37.5 months. Overall, 92.3% of the patients went
      on to fusion. Two patients (7.7%) had a delayed union and 2 patients had a
      nonunion (7.7%) and were considered operative failures. There were 3 repeat
      procedures related to the arthrodesis procedure: 1 conversion of a subtalar to a
      triple arthrodesis, 1 revision talonavicular fusion, and 1 revision subtalar
      fusion. The average time to weight bearing after arthrodesis was 8.7 weeks; the
      mean time to radiographic and clinical fusion was 26.5 weeks. There were no
      secondary complications associated with the arthrodesis. Pain and functional
      outcome scores improved significantly. There were no differences in the rates of
      subsequent fusions among implant choices, though the time to fusion in the mobile
      bearing prosthesis was significantly longer than the 2 fixed-bearing prostheses.
      Compared with the data of 13 patients with prior ipsilateral ankle arthrodeses
      and subtalar fusions, patients who had an ankle replacement had a higher fusion
      rate (P = .03) and had a similar time to fusion. CONCLUSION: Hindfoot arthrodesis
      following a TAR was safe and effective in improving function and pain.
      Additionally, a hindfoot arthrodesis following a TAR had a higher fusion rate
      than a subtalar fusion following an ankle arthrodesis. Although the time to
      healing was relatively long, various hindfoot fusions were used to treat
      progressive arthritis and deformity with high fusion rates. LEVEL OF EVIDENCE:
      Level III, comparative case series.

PMID- 27030232
TI  - Quo Vadis? Perspectives on the Future of Foot & Ankle Fellowship Training.

PMID- 27030233
TI  - Indian doctor is arrested for not attending court hearing 24 years ago.

PMID- 27030234
TI  - Factors Associated With Frequent Emergency Department Use in the Medicare
      Population.
AB  - Frequent emergency department (ED) use is a public health and policy relevant
      concern but has not previously been examined in the Medicare population. We
      conducted a retrospective, claims-based analysis of a nationally representative
      20% sample of fee-for-service Medicare beneficiaries in 2010 ( n = 5,778,038) to
      examine frequent ED use. We used multinomial logistic regression to study the
      relationship between frequent ED use and sociodemographic, outpatient care, and
      clinical characteristics. Factors that were most strongly associated with
      frequent ED use included being age 18 to 34 years compared with 65 to 74 years
      (relative risk ratio = 20.5, confidence interval [CI; 19.7, 21.3]) and mental
      illness (relative risk ratio = 6.8, CI [6.7, 6.9]). Low versus high continuity of
      care was associated with 24% (95% CI [1.21, 1.26]) greater risk of frequent
      compared with non-ED use. Although clinical and demographic characteristics are
      most strongly associated with frequent ED use, poor continuity of care is also a
      contributor.

PMID- 27030235
TI  - Changes in dissolved organic matter composition and metabolic diversity of
      bacterial community during the degradation of organic matter in swine effluent.
AB  - In this study, an incubation experiment was conducted with effluent collected
      from the concentrated swine-feeding operations (CSFOs) located in Yujiang County
      of Jiangxi Province, China. The purpose of this study was to elucidate the
      relationships between the composition of dissolved organic matter (DOM) and the
      community-level physiological profiles (CLPPs) of microorganisms in swine
      effluent. For all samples examined, the concentrations of dissolved organic
      carbon (DOC) and total dissolved nitrogen (TDN) were decreased by an average of
      58.2 +/- 30.4 and 49.2 +/- 38.7 %, whereas total dissolved phosphorus (TDP)
      exhibited an average final accumulation of 141.5 +/- 43.0 %. In the original
      samples, ammonium nitrogen accounted for 88.9 +/- 4.9 % of the TDN, which was
      reduced to a final average of 83.9 +/- 9.6 %. Two protein-like (tyrosine and
      tryptophan) and two humic-like (fulvic acids and humic acids) components were
      identified using a three-dimensional excitation-emission matrix. With the
      increase in incubation time, the relative concentrations of two protein-like
      components in effluent were reduced by an average of 83.2 +/- 24.7 %. BIOLOG(TM)
      ECO plates were used to determine the metabolic fingerprint of the bacterial
      community, and a shift in the utilization patterns of substrates was observed
      over the study period. Additionally, the Shannon-Wiener index of CLPP was
      ultimately reduced by an average of 43.5 +/- 8.5 %, corresponding to the
      metabolic diversity of the bacterial community. The redundancy analysis
      identified significant relationships between environmental parameters and the
      CLPP of microorganisms. To a certain degree, the DOM compositions were linked
      with the substrate utilization patterns of the bacterial community during the
      degradation of organic matter in swine effluent. 

PMID- 27030236
TI  - Carbon dioxide emissions, GDP, energy use, and population growth: a multivariate
      and causality analysis for Ghana, 1971-2013.
AB  - In this study, the relationship between carbon dioxide emissions, GDP, energy
      use, and population growth in Ghana was investigated from 1971 to 2013 by
      comparing the vector error correction model (VECM) and the autoregressive
      distributed lag (ARDL). Prior to testing for Granger causality based on VECM, the
      study tested for unit roots, Johansen's multivariate co-integration and performed
      a variance decomposition analysis using Cholesky's technique. Evidence from the
      variance decomposition shows that 21 % of future shocks in carbon dioxide
      emissions are due to fluctuations in energy use, 8 % of future shocks are due to
      fluctuations in GDP, and 6 % of future shocks are due to fluctuations in
      population. There was evidence of bidirectional causality running from energy use
      to GDP and a unidirectional causality running from carbon dioxide emissions to
      energy use, carbon dioxide emissions to GDP, carbon dioxide emissions to
      population, and population to energy use. Evidence from the long-run elasticities
      shows that a 1 % increase in population in Ghana will increase carbon dioxide
      emissions by 1.72 %. There was evidence of short-run equilibrium relationship
      running from energy use to carbon dioxide emissions and GDP to carbon dioxide
      emissions. As a policy implication, the addition of renewable energy and clean
      energy technologies into Ghana's energy mix can help mitigate climate change and
      its impact in the future. 

PMID- 27030237
TI  - Investigation of ammonium adsorption on Algerian natural bentonite.
AB  - Adsorption of several chemical contaminants onto clay minerals is the most
      recommended technique applied in the wastewater treatment field, owing to its low
      economic cost, efficiency, and low power consumption. In this context, natural
      bentonite particles with 80-MUm diameter were investigated for the ammonium
      adsorption in aqueous solution using an incubator that kept the constant
      temperature and stirring speed at 200 RPM. The study of different experimental
      parameters effect on the adsorption process revealed that the raw bentonite have
      adsorbed approximately 53.36 % of the initial ammonium concentration at pH 7 and
      temperature of 30  degrees C. This percentage has been improved by increasing the
      adsorbent dosage in solution, which could reach up to 81.2 % at 40 g/L of
      bentonite with an initial ammonium concentration of 10 mg-NH4+/L. Moreover,
      experimental data modeling allowed us to conclude that the adsorption isotherm
      obeys to both models of Langmuir and Freundlich.

PMID- 27030238
TI  - Phytoremediation of Cu and Zn by vetiver grass in mine soils amended with humic
      acids.
AB  - Phytoremediation of contaminated mine soils requires the use of fast-growing,
      deep-rooted, high-biomass, and metal-tolerant plants with the application of soil
      amendments that promote metal uptake by plants. A pot experiment was performed to
      evaluate the combined use of vetiver grass (Chrysopogon zizanioides) and humic
      acid for phytoremediation of Cu and Zn in mine soils. Vetiver plants were grown
      in soil samples collected from two mine sites of Spain mixed with a commercial
      humic acid derived from leonardite at doses of 0, 2, 10, and 20 g kg(-1). Plant
      metal concentrations and biomass were measured and metal bioavailability in soils
      was determined by a low molecular weight organic acid extraction. Results showed
      that humic acid addition decreased organic acid-extractable metals in soil.
      Although this extraction method is used to estimate bioavailability of metals, it
      was not a good estimator under these conditions due to competition with the
      strong chelators in the added humic acid. High doses of humic acid also promoted
      root growth and increased Cu concentrations in plants due to formation of soluble
      metal-organic complexes, which enhanced removal of this metal from soil and its
      accumulation in roots. Although humic acid was not able to improve Zn uptake, it
      managed to reduce translocation of Zn and Cu to aerial parts of plants. Vetiver
      resulted unsuitable for phytoextraction, but our study showed that the combined
      use of this species with humic acid at 10-20 g kg(-1) could be an effective
      strategy for phytostabilization of mine soils. 

PMID- 27030239
TI  - Photochemical defluorination of aqueous perfluorooctanoic acid (PFOA) by
      Fe(0)/GAC micro-electrolysis and VUV-Fenton photolysis.
AB  - Perfluorooctanoic acid (PFOA) is extremely persistent and bioaccumulative in the
      environment; thus, it is very urgent to investigate an effective and moderate
      technology to treat the pollution of PFOA. In this study, a process combined iron
      and granular activated carbon (Fe(0)/GAC) micro-electrolysis with VUV-Fenton
      system is employed for the remediation of PFOA. Approximately 50 % PFOA (10 mg L(
      1)) could be efficiently defluorinated under the following conditions: pH 3.0,
      dosage of Fe 7.5 g L(-1), dosage of GAC 12.5 g L(-1), and concentration of H2O2
      22.8 mmol L(-1). Meanwhile, during the process, evident defluorination was
      observed and the concentration of fluoride ion was eventually 3.23 mg L(-1). The
      intermediates including five shorter-chain perfluorinated carboxylic acids
      (PFCAs), i.e., C7, C6, C5, C4, and C3, were also analyzed by high-performance
      liquid chromatography tandem mass spectrometry (HPLC/MS/MS) and defluorination
      mechanisms of PFOA was proposed, which involved photochemical of OH., direct
      photolysis (185-nm VUV), and photocatalytic degradation of PFOA in the presence
      of Fe(3+) (254-nm UV). 

PMID- 27030240
TI  - Factors influencing arsenic concentrations and species in mangrove surface
      sediments from south-east NSW, Australia.
AB  - Arsenic concentrations and speciation of 55 mangrove surface sediment samples
      from the south-eastern coast of NSW, Australia, have been measured. Arsenic
      concentrations were in the range 1.6-8.6 MUg/g dry mass. All arsenic
      concentration values were well below 20 MUg/g, the ANZEC/ARMCANZ interim sediment
      quality guideline-low trigger value. The bulk sediment pH was 6.0-7.3 and Eh -80
      to -260 mV. The sediments contained variable silt-clay (2-30 % w/w), iron (668
      12721 MUg/g), manganese (1-115 MUg/g), sulphur (70-18400 MUg/g) and carbon (5-90
      mg/g) concentrations. Arsenic concentrations correlated with silt and clay
      content, iron and manganese concentrations, indicating silt-clay particles
      covered and coated with iron and manganese (oxy) hydroxides scavenged arsenic.
      Arsenic extracted with 0.5 M phosphoric acid (68-95 %) was present only as
      inorganic arsenic (55-91 %), indicating that other arsenic species such as
      arsenobetaine derived from marine animal tissues rapidly degrade in sediments.
      The unextractable arsenic was correlated with increases in organic carbon, iron
      and manganese content. In conclusion, the cycling of arsenic in mangrove
      sediments is essentially the cycling of inorganic arsenic and primarily
      controlled by the redox cycling of carbon, sulphur, iron and manganese.

PMID- 27030241
TI  - Association between serum vitamin D levels and the risk of kidney stone: evidence
      from a meta-analysis.
AB  - BACKGROUND: Many epidemiological studies have conducted to evaluate the
      association between serum vitamin D levels and the risk of kidney stone. The aim
      of this study was to summarize the evidence from epidemiological studies between
      them. METHODS: Pertinent studies were identified by a search of PubMed, Embase,
      the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China
      Biology Medical literature up to July 2015. Standardized mean difference (SMD)
      was conducted to combine the results. Random-effect model was used. Publication
      bias was estimated using Egger's regression asymmetry test. RESULTS: Seven
      articles involving 451 kidney stone cases and 482 controls were included in this
      meta-analysis. Our pooled results suggested that kidney stone patients had a
      significantly higher serum vitamin D level compared with controls [summary SMD =
      0.65, 95 % CI = 0.51, 0.79, I(2) = 97.0 %]. The associations were also
      significant both in Europe [SMD = 0.35, 95 % CI = 0.17, 0.53] and in Asia [SMD =
      1.00, 95 % CI = 0.76, 1.25]. No publication bias was found. CONCLUSIONS: Our
      analysis indicated that serum vitamin D level in kidney stone patients was
      significantly higher than that in non-kidney stone controls, both in Europe and
      Asia populations.

PMID- 27030242
TI  - Occupational chemical exposure and diabetes mellitus risk.
AB  - Diabetes mellitus (DM) is a group of metabolic diseases that may originate from
      an interaction between genetic and lifestyle risk factors. However, the possible
      role of occupational chemical exposures in the disease development and
      progression remains unclear. Therefore, this review aimed to provide a
      comprehensive evaluation of the relationship between occupational exposure to
      specific chemical substances or industrial activities and DM morbidity and
      mortality outcomes. Although some positive findings may support the diabetogenic
      role of certain pesticides and dioxins in different workplaces, the variable
      conditions of exposure, the lack of quantitative environmental or biological
      monitoring data and the different outcomes evaluated do not allow defining a
      specific exposure-disease causality. Therefore, further epidemiological studies
      will be necessary to adequately assess modes of action for different substances,
      dose-response relationships as well as individual susceptibility factors
      potentially affecting the exposure-disease continuum. Overall, this appears
      important to adequately assess, communicate and manage risks in occupational
      chemical exposure settings with the aim to protect workers and build healthier
      job conditions for diabetic employees.

PMID- 27030243
TI  - How we do it: double in situ split for staged mesohepatectomy in patients with
      advanced gall bladder cancer and marginal future liver remnant.
AB  - PURPOSE: Associating liver partition with portal vein ligation for staged
      hepatectomy (ALPPS) has increased the rate of liver resections in patients with
      marginal future liver remnant. We here describe a modified ALPPS procedure with
      splitting-off the central liver segments for staged mesohepatectomy in patients
      with advanced gall bladder cancer. METHODS: A double in situ split for ALPPS
      (DALPPS) is performed with splitting-off the central liver segments (segments 1,
      4, 5, and 8). This induces a rapid hypertrophy of the left lateral (segments 2/3)
      and right posterior sectors (segments 6/7). An intrahepatic right posterior
      approach during splitting-off the right posterior sector is introduced as a part
      of this new procedure. This approach facilitates the dissection and ligation of
      the right anterior branch of the portal vein (segments 5 and 8) while the liver
      hilum remains untouched during the first step of surgery. RESULTS: Two patients
      with advanced gall bladder cancer were treated with the DALPPS procedure till
      date. After a short interval (7-9 days), a rapid hypertrophy of the left lateral
      and right posterior sector was observed (hypertrophy up to 72.6 and 54.6 %,
      respectively). A staged mesohepatectomy including caudate lobectomy and resection
      of the extrahepatic bile duct was then performed safely. There was no surgical
      technical morbidity. No signs of posthepatectomy liver failure according to the
      50-50 criteria were seen. However, one patient died from severe ARDS attributed
      to the preoperative chemotherapy. Nevertheless, this complication is deemed to be
      surgery related. CONCLUSIONS: The DALPPS procedure is a new surgical technique
      for staged mesohepatectomy for patients with small future liver remnant in size
      or in function. However, appropriate patient selection is mandatory to avoid
      morbidity and mortality.

PMID- 27030244
TI  - Evaluation of neuropsychological outcome and "quality of life" after glioma
      surgery.
AB  - PURPOSE: Extended tumour resection is imperative to improve the outcome of glioma
      patients but also carries the risk of increasing morbidity and thus, potentially,
      of decreasing the patient's quality of life (QOL). In this pilot study, we
      evaluated how postoperative neurological and neuropsychological alterations
      impacted on QOL in patients who underwent glioma resection. METHODS: Twenty-two
      patients were included in this study and tested at three different time points,
      i.e. 1 day before surgery (t1), on the day of discharge (t2) and 3 months
      following surgery (T3). National Institutes of Health Stroke Scale (NIHSS) score,
      Addenbrook's Cognitive Examination-Revised (ACE-R) and a comprehensive battery of
      established tests were used to assess neurological and neuropsychological
      profiles. QOL and subjectively experienced health condition were ascertained
      through the European Organization for Research and Treatment of Cancer Quality of
      Life Questionnaire C30 (EORTC-QLQ C30) and EORTC-QLQ BN20 questionnaires.
      RESULTS: Postoperatively, 5/22 patients worsened and 5/22 patients improved
      neurologically. Depending on the neuropsychological test, up to 57.1 % of
      patients experienced deterioration of some sort of neuropsychological function.
      Most of these functions, however, recovered during the extended observation
      period (3 months). There was no correlation between QOL and a patient's
      neurological or neuropsychological condition. CONCLUSIONS: Our study suggests
      that extended tumour resection is not necessarily linked to a loss in QOL.

PMID- 27030245
TI  - Efficacy of transanal tube placement after anterior resection for rectal cancer:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Anastomotic leakage is a serious complication that can occur after
      anterior resection of the rectum. There is a question regarding whether the
      placement of a transanal tube can decrease the rate of anastomotic leakage. The
      aim of this systematic review and meta-analysis was to evaluate the efficacy of
      transanal tube placement after anterior resection. METHODS: We searched three
      major databases (PubMed, Embase, and the Cochrane Library) up until January 2015
      for studies evaluating the benefit of transanal tubes after anterior resection
      for rectal cancer. The primary outcome measure was the rate of clinical
      anastomotic leakage. Secondary outcome was the rate of reoperation. Pooled risk
      ratios (RR) with 95% confidence intervals (CI) were obtained using random effects
      models. RESULTS: One randomized controlled trial and three observational studies
      involving 909 patients met inclusion criteria. Clinical anastomotic leakage
      occurred in 3.49% (14 of 401) of patients with transanal tubes and 12.01% (61 of
      508) of patients without transanal tubes. Meta-analysis of the studies showed a
      lower risk of anastomotic leakage (RR, 0.32; 95% CI 0.18-0.58) and reoperation
      related to leakage (RR, 0.19; 95% CI 0.08-0.46) when the transanal tube was
      placed. CONCLUSIONS: While studies are few and mostly observational, the data to
      date indicate that placement of a transanal tube decreases the rate of clinical
      anastomotic leakage and reoperation related to leakage. More studies are needed
      to confirm these findings.

PMID- 27030246
TI  - Endoscopic management of internally migrated pancreatic duct stents (with video).
AB  - BACKGROUND AND AIMS: Spontaneous intestinal migration of pancreatic stents is a
      known phenomenon. However, retrieval of a proximally migrated pancreatic stent
      (PMPS) poses a therapeutic challenge. The primary aim of this study was to
      evaluate technical success of endoscopic retrograde of cholangiopancreatography
      (ERCP) for extraction of PMPS, including number of sessions, need of surgery for
      failures and intervention-induced adverse events. The secondary outcome was to
      evaluate long-term effects of PMPS on the ductal morphology. METHODS: Data of
      patients undergoing pancreatic stenting since January 2007 was reviewed. Fourteen
      patients were found to have PMPS. The level of stent migration was divided into
      two categories: level 1: retropapillary migration of the stent, the distal end
      seen till the genu (n = 6). Level II: PMPS with distal end seen beyond genu (n =
      8). The stents were placed due to following reasons, prophylactic pancreatic
      stenting after common bile duct stone extraction (n = 6), pancreatic endotherapy
      for chronic pancreatitis (n = 7), and recurrent acute pancreatitis with
      incomplete pancreas divisum (n = 1). ERCP was done using Olympus TJF 160/180
      duodenoscope. Stent extraction was initially attempted using rat tooth forceps,
      snare with or without wire, wire-guided basket, and in case of failures,
      pancreatoscope was used (Boston Scientific, USA). RESULTS: PMPS could
      successfully be retrieved in 13 out of 14 patients (92.8 %). Stents were
      retrieved using stone extraction balloon in two (14.2 %), modified angiography
      balloon in one (7 %), rat tooth in three patients (21.4 %), over-the-wire snare
      in three patients (21.4 %), lasso technique in one (7 %), and under
      pancreatoscope guidance in three patients (21.4 %). Adverse events encountered
      were mild pancreatitis (n = 2, 14 %) and self-limited bleeding (n = 2, 14 %).
      CONCLUSIONS: Endotherapy of PMPS could be complex and associated with adverse
      events. Level II-migrated stents may require specialized methods like
      pancreatoscopy for stent retrieval.

PMID- 27030247
TI  - Onchocerciasis, an undiagnosed disease in Mozambique: identifying research
      opportunities.
AB  - BACKGROUND: The objective of this paper is to summarise and critically review the
      available data about onchocerciasis in Mozambique, in order to report
      epidemiological and clinical aspects related to the disease and identify gaps in
      knowledge. The paper is intended to raise awareness of the existence and
      importance of this disease and to define research priorities. METHODS: We
      examined the scarce epidemiological data at our disposal: two diagnostic studies
      in 1997 and 1998 (first reports on the existence of onchocerciasis in
      Mozambique), and two Rapid Epidemiological Mapping of Onchocerciasis (REMO)
      surveys in 2001 and 2007. We examined differences in study designs and
      methodologies as well as the differing geographical locations to explain the
      divergence in findings among the studies. RESULTS: Evidence indicates that
      onchocerciasis is hypoendemic in Mozambique (with national and imported cases),
      but still largely remains an undiagnosed illness. There is no awareness of the
      clinical aspects of the disease and nor of the differential diagnosis with
      lepromatous leprosy and dermatitis caused by Scabies spp. The use of skin biopsy
      and a symptom screening questionnaire, combined with nodule rate, in the first
      two studies may have captured even atypical or subacute presentations. Both REMO
      surveys relied solely on nodule detection and in the six years between the two
      studies, the prevalence of nodules detected more than doubled. CONCLUSIONS: The
      epidemiology and clinical aspects of the disease are unknown in Mozambique. Since
      the last REMO took place in 2007 and since the population is subject to large
      scale movement and displacement, it is important to develop tools to identify and
      analyse populations that are at high risk for onchocerciasis. Cases of
      onchocerciasis may be misdiagnosed as leprosy or scabies that fail to improve
      despite being subjected to treatment against leprosy. Techniques to enable a
      differential diagnosis need to be established by training health professionals on
      the recognition of this undiagnosed disease. It is equally necessary to identify
      the blackfly vectors and where they breed.

PMID- 27030248
TI  - Topology based identification and comprehensive classification of four
      transmembrane helix containing proteins (4TMs) in the human genome.
AB  - BACKGROUND: Membrane proteins are key components in a large spectrum of diverse
      functions and thus account for the major proportion of the drug-targeted portion
      of the genome. From a structural perspective, the alpha-helical transmembrane
      proteins can be categorized into major groups based on the number of
      transmembrane helices and these groups are often associated with specific
      functions. When compared to the well-characterized seven-transmembrane containing
      proteins (7TM), other TM groups are less explored and in particular the 4TM
      group. In this study, we identify the complete 4TM complement from the latest
      release of the human genome and assess the 4TM structure group as a whole. We
      functionally characterize this dataset and evaluate the resulting groups and
      ubiquitous functions, and furthermore describe disease and drug target
      involvement. RESULTS: We classified 373 proteins, which represents ~7 % of the
      human membrane proteome, and includes 69 more proteins than our previous
      estimate. We have characterized the 4TM dataset based on functional, structural,
      and/or evolutionary similarities. Proteins that are involved in transport
      activity constitute 37 % of the dataset, 23 % are receptor-related, and 13 % have
      enzymatic functions. Intriguingly, proteins involved in transport are more than
      double the 15 % of transporters in the entire human membrane proteome, which
      might suggest that the 4TM topological architecture is more favored for
      transporting molecules over other functions. Moreover, we found an interesting
      exception to the ubiquitous intracellular N- and C-termini localization that is
      found throughout the entire membrane proteome and 4TM dataset in the
      neurotransmitter gated ion channel families. Overall, we estimate that 58 % of
      the dataset has a known association to disease conditions with 19 % of the genes
      possibly involved in different types of cancer. CONCLUSIONS: We provide here the
      most robust and updated classification of the 4TM complement of the human genome
      as a platform to further understand the characteristics of 4TM functions and to
      explore pharmacological opportunities.

PMID- 27030249
TI  - Rasagiline for mild cognitive impairment in Parkinson's disease: A placebo
      controlled trial.
AB  - BACKGROUND: This study's aims were to determine the efficacy and tolerability of
      rasagiline, a selective monoamine oxidase inhibitor B, for PD patients with mild
      cognitive impairment. METHODS: Patients on stable dopaminergic therapy were
      randomized to adjunct rasagiline 1 mg/day or placebo in this 24-week, double
      blind, placebo-controlled, multisite study. The primary endpoint was mean change
      from baseline to week 24 on the Scales for Outcomes of Parkinson's Disease
      Cognition total score. Key secondary measures included changes in cognition,
      activities of daily living, motor scores, and Clinical Global Impression of
      Change, as well as safety and tolerability measures. RESULTS: Of the 170 patients
      randomized, 151 (88.2%) completed the study. Change in Scales for Outcomes of
      Parkinson's Disease-Cognition scores were not significantly different in the
      rasagiline and placebo groups (adjusted mean: 1.6 [standard error {SE} = 0.5] vs.
      0.8 [SE = 0.5] points; LS means difference = 0.8; 95% confidence interval: -0.48,
      2.05; P = 0.22). There were no between-group differences in change in the MoCA
      (p=0.84) or Penn Daily Activities Questionnaire (P = 0.48) scores or in the
      distribution of Alzheimer's Disease Cooperative Study-Clinical Global Impression
      of Change modified for mild cognitive impairment (P = 0.1). Changes in motor
      (UPDRS part III; P = 0.02) and activities of daily living (UPDRS part II; P <
      0.001) scores favored rasagiline. Rasagiline was well tolerated; the most common
      adverse events in both groups were falls and dizziness. CONCLUSIONS: Rasagiline
      treatment in PD patients with mild cognitive impairment was not associated with
      cognitive improvement. Rasagiline did not worsen cognition, improved motor
      symptoms and activities of daily living, and was well tolerated in elderly
      cognitively impaired patients. (c) 2016 International Parkinson and Movement
      Disorder Society.

PMID- 27030250
TI  - Carglumic acid enhances rapid ammonia detoxification in classical organic
      acidurias with a favourable risk-benefit profile: a retrospective observational
      study.
AB  - BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic
      aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic
      acid metabolism induces hyperammonaemia arising partly from secondary deficiency
      of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is
      required to prevent neurological complications. This retrospective, multicentre,
      open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of
      carglumic acid, a synthetic structural analogue of NAG, for treating
      hyperammonaemia during OA decompensation. METHODS: Eligible patients had
      confirmed OA and hyperammonaemia (plasma NH3 > 60 MUmol/L) in >=1 decompensation
      episode treated with carglumic acid (dose discretionary, mean (SD) first dose
      96.3 (73.8) mg/kg). The primary outcome was change in plasma ammonia from
      baseline to endpoint (last available ammonia measurement at <=18 hours after the
      last carglumic acid administration, or on Day 15) for each episode. Secondary
      outcomes included clinical response and safety. RESULTS: The efficacy population
      (received >=1 dose of study drug and had post-baseline measurements) comprised 41
      patients (MMA: 21, PA: 16, IVA: 4) with 48 decompensation episodes (MMA: 25, PA:
      19, IVA: 4). Mean baseline plasma ammonia concentration was 468.3 (+/-365.3)
      MUmol/L in neonates (29 episodes) and 171.3 (+/-75.7) MUmol/L in non-neonates (19
      episodes). At endpoint the mean plasma NH3 concentration was 60.7 (+/-36.5)
      MUmol/L in neonates and 55.2 (+/-21.8) MUmol/L in non-neonates. Median time to
      normalise ammonaemia was 38.4 hours in neonates vs 28.3 hours in non-neonates and
      was similar between OA subgroups (MMA: 37.5 hours, PA: 36.0 hours, IVA: 40.5
      hours). Median time to ammonia normalisation was 1.5 and 1.6 days in patients
      receiving and not receiving concomitant scavenger therapy, respectively. Although
      patients receiving carglumic acid with scavengers had a greater reduction in
      plasma ammonia, the endpoint ammonia levels were similar with or without
      scavenger therapy. Clinical symptoms improved with therapy. Twenty-five of 57
      patients in the safety population (67 episodes) experienced AEs, most of which
      were not drug-related. Overall, carglumic acid seems to have a good safety
      profile for treating hyperammonaemia during OA decompensation. CONCLUSION:
      Carglumic acid when used with or without ammonia scavengers, is an effective
      treatment for restoration of normal plasma ammonia concentrations in
      hyperammonaemic episodes in OA patients.

PMID- 27030252
TI  - The Link Between Klebsiella and Ankylosing Spondylitis in Worldwide Geographical
      Locations.
AB  - Ankylosing spondylitis (AS) is a world-wide chronic inflammatory disease of the
      axial skeleton most likely caused by a microbial factor in genetically
      susceptible individuals. Over the last 40 years extensive data has been produced
      which shows that the majority of patients with AS possess the HLA-B27 genetic
      marker. Significantly elevated levels of Klebsiella antibodies have been
      demonstrated in 1556 AS patients in 16 different countries with various
      geographical locations. Other evidence for the link between Klebsiella and AS
      include increased fecal isolation rates of Klebsiella microbes in AS patients
      together with shared molecular and immunological cross-reactivity features
      existing between Klebsiella antigens and HLA-B27 and collagens I, III and IV.
      Anti-Klebsiella measures could possibly be included with the currently used
      medical treatment in the management of patients with AS.

PMID- 27030251
TI  - Health professionals' perceptions of the barriers and facilitators to providing
      smoking cessation advice to women in pregnancy and during the post-partum period:
      a systematic review of qualitative research.
AB  - BACKGROUND: Reducing smoking in pregnancy is a policy priority in many countries
      and as a result there has been a rise in the development of services to help
      pregnant women to quit. A wide range of professionals are involved in providing
      these services, with midwives playing a particularly pivotal role. Understanding
      professionals' experiences of providing smoking cessation support in pregnancy
      can help to inform the design of interventions as well as to improve routine
      care. METHODS: A synthesis of qualitative research of health professionals'
      perceptions of the barriers and facilitators to providing smoking cessation
      advice to women in pregnancy and the post-partum period was conducted using meta
      ethnography. Searches were undertaken from 1990 to January 2015 using terms for
      maternity health professionals and smoking cessation advisors, pregnancy, post
      partum, smoking, and qualitative in seven electronic databases. The review was
      reported in accordance with the 'Enhancing transparency in reporting the
      synthesis of qualitative research' (ENTREQ) statement. RESULTS: Eight studies
      reported in nine papers were included, reporting on the views of 190 health
      professionals/key informants, including 85 midwives and health visitors. The
      synthesis identified that both the professional role of participants and the
      organisational context in which they worked could act as either barriers or
      facilitators to an individual's ability to provide smoking cessation support to
      pregnant or post-partum women. Underpinning these factors was an acknowledgment
      that the association between maternal smoking and social disadvantage was a
      considerable barrier to addressing and supporting smoking cessation CONCLUSIONS:
      The review identifies a role for professional education, both pre-qualification
      and in continuing professional development that will enable individuals to
      provide smoking cessation support to pregnant women. Key to the success of this
      education is recognising the centrality of the professional-client/patient
      relationship in any interaction. The review also highlights a widespread
      professional perception of the barriers associated with helping women give up
      smoking in pregnancy, particularly for those in disadvantaged circumstances.
      Improving the quality and accessibility of evidence on effective healthcare
      interventions, including evidence on 'what works' to support smoking cessation in
      disadvantaged groups, should therefore be a priority. PROSPERO 2013:
      CRD42013004170.

PMID- 27030253
TI  - Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients
      Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.
AB  - OBJECTIVE: Podoplanin (PDPN) mediates tumor cell migration and invasion, which
      phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore,
      the precise cellular distribution of PDPN and it's relationships with
      inflammation was studied in RA treated with biologic disease-modifying anti
      rheumatic drugs (DMARD) or conventional DMARDs (cDMARD). METHODS: PDPN+ cells
      were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%
      20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20)
      or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell
      grading of inflammation and cell-typing. RESULTS: Inflammatory synovitis score
      was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were
      found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates
      (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and
      cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was
      expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells
      in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA.
      CONCLUSION: PDPN was markedly increased in the immunologically inflamed RA
      synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN
      may have potential of a new marker of residual arthritis in local joints for
      inflammation-associated severe RA.

PMID- 27030254
TI  - The Emerging Role of Bradykinin in the Pathogenesis of Osteoarthritis and its
      Possible Clinical Implications.
AB  - Osteoarthritis (OA) is a multifaceted disorder defined by the alteration of
      homeostasis and degradation in articular cartilage. Recently mounting evidence
      suggests that OA should be conceived as an inflammatory disease rather than a
      simple wear-and-tear problem. Bradykinin (BK) and B2 receptors play a role in the
      pathogenesis of OA. The aim of this paper is to analyze preclinical and clinical
      studies examining the potential role of BK and of B2 receptor blockade in OA
      pathogenesis. We analyzed the data about the effects of BK in synoviocytes,
      endothelial cells and chondrocytes cultures and described the action of B2
      receptor antagonists (Icatibant and Fasitibant). In conclusion, the BK is an
      endogenous proinflammatory molecule that is involved in the pathophysiology of
      OA, and B2 receptor antagonists are believed to be considered as a potential
      symptomatic therapy for this disease. There is a need for further preclinical and
      clinical trials to better explain the mechanisms of action and the efficacy and
      tolerability of the B2 receptor antagonists in OA.

PMID- 27030255
TI  - Correlation of Bone Mineral Density Scores and Proton Pump Inhibitors Use in the
      Elderly.
AB  - OBJECTIVE: We aimed to identify any correlation between long-term proton pump
      inhibitor use and low bone mineral density in the elderly. MATERIALS AND METHODS:
      This is a retrospective cohort study looking at PPI usage and bone mineral
      density scores of patients age 65 and above within a period of two years. Lumbar
      spine, right hip, and left hip bone mineral density t-scores were reviewed in PPI
      users and non-users. RESULTS: A total of 1,016 patients who had bone mineral
      density scans within that period were identified. Non-adjusted data showed no
      statistically significant association between PPI users and non-users in lumbar
      spine (p = 0.903), right hip (p = 0.775) and left hip (p = 0.407) bone mineral
      density scores. After adjusting for age and gender, PPI use was still not
      associated with low bone mineral density at the lumbar spine (p = 0.957), right
      hip (p = 0.440), or left hip (p = 0.691). Thelogistic regression did not show a
      statistically significant difference in low bone mineral density scores in lumbar
      spine (p= 0.162), right hip (p = 0.796), and left hip (p = 0.196) when length of
      use was considered. CONCLUSION: Among adults 65 years and older proton pump
      inhibitors users; there appears to be no correlation betweenPPI use and low bone
      mineral density and/or the length of PPI use.

PMID- 27030256
TI  - SERUM CALPROTECTIN LEVELS AS A MARKER OF ARTHRITIS: AN ITALIAN EXPERIENCE.
AB  - BACKGROUND: The identification and validation of soluble markers provide
      significant opportunities for managing patients with rheumatic diseases, and
      calprotectin may be an alternative laboratory biomarker of inflammatory
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA) even though its levels
      may vary considerably. The aim of this study was to propose a calprotectin cut
      off value that would be useful for distinguishing patients with inflammatory
      arthritis or non-inflammatory arthritis (NIA) in clinical practice. METHODS: A
      commercial enzyme-linked immunosorbent assay was used to measure serum
      calprotectin levels in patients with RA, ankylosing spondylitis (AS), PsA and
      controls with NIA. All of the patients had been treated with biological disease
      modifying anti-rheumatic drugs (DMARDs) for about 12 months after previous
      failure on conventional DMARDs. RESULTS: Receiver operating characteristic (ROC)
      analysis showed that serum calprotectin levels significantly differentiated the
      samples of the patients with inflammatory rheumatic disease from those of the
      controls. A serum calprotectin level of > 0.9 MUg/mL (the optimal predictive cut
      off value in the ROC analysis) had a sensitivity of 95.3%, a specificity of
      82.2%, a positive likelihood ratio (LR) of 5.35 and a negative LR of 0.057.
      CONCLUSIONS: Our findings suggest that serum calprotectin levels are useful in
      clinical practice to distinguish patients with inflammatory arthritis and NIA.
      Further studies of a larger population are suggested.

PMID- 27030257
TI  - Weight bearing joints destruction in rheumatoid arthritis.
AB  - In many cases of rheumatoid arthritis (RA) joints of the upper extremities are
      affected. However, involvement of weight bearing joints of the lower extremities
      is strongly associated with a decreased activities of daily living ability such
      as gait disorder. Once the progression of weight bearing joint destruction
      occurs, lower extremity function will decrease even if RA disease activity is
      improved by pharmacotherapy. In this article, we investigated joint destruction
      suppressing effects of pharmacotherapy on the hip and knee joints, as well as
      risk factors for joint destruction. We also discuss surgical treatment strategies
      and clinical outcomes for progressive joint destruction.

PMID- 27030258
TI  - Incidence of esophageal cancer in Sri Lanka: Analysis of cancer registry data and
      comparison with other South Asian populations.
AB  - INTRODUCTION: The objectives of this study were to report the incidence of
      Carcinoma of Esophagus (CaE) in Sri Lanka and to compare these values with other
      cancer registry data of the region and with migrant populations. MATERIALS AND
      METHODS: We compared the data published by the National Cancer Control Program
      over the last two decades with data from the National Cancer Registry Programme
      of the Indian Council of Medical Research and Karachi Cancer Registry. SEERstat
      was used to analyze the surveillance, epidemiology and end results database to
      analyze data on Indian migrant population. RESULTS: CaE was the fourth most
      common cancer overall and among females and third most common cancer among males.
      The incidence of CaE rises with age in both sexes, with a peak in the 70-74 year
      age group. There was a disproportionately higher number of CaE in the Tamil
      population (chi-square test, P < 0.00001). The commonest type of CaE in Sri Lanka
      was squamous cell carcinoma, Not otherwise specified (NOS) (n = 750, 70.5%),
      followed by adenocarcinoma, NOS (n = 83, 7.8%). India, Pakistan and Sri Lanka
      have comparable age-adjusted incidence and age distribution of CaE. All migrant
      populations had lower incidence of CaE than original population or population in
      their present country. Both cigarette smoking and alcohol consumption are more
      prevalent in Sri Lankan males than females. DISCUSSION AND CONCLUSIONS: The
      incidence of CaE and its distribution among age groups in Sri Lanka was
      comparable to other countries of the region. Persons of Tamil ethnicity have a
      higher risk of developing CaE.

PMID- 27030259
TI  - Local charge states in hexagonal boron nitride with Stone-Wales defects.
AB  - A Stone-Wales (SW) defect is the simplest topological defect in graphene-like
      materials and can be potentially employed to design electronic devices . In this
      paper, we have systematically investigated the formation, structural, and
      electronic properties of the neutral and charged SW defects in hexagonal boron
      nitride (BN) using first-principles calculations. The transition states and
      energy barrier for the formation of SW defects demonstrate that the defected BN
      is stable. Our calculations show that there are two in-gap defect levels, which
      originate from the asymmetrical pentagon-heptagon pairs. The local defect
      configurations and electronic properties are sensitive to their charge states
      induced by the defect levels. The electronic band structures show that the
      negative and positive charged defects are mainly determined by shifting the
      conduction band minimum (CBM) and valence band maximum (VBM) respectively, and
      the SW-defected BN can realize -1 and +1 spin-polarized charge states. The
      effects of carbon (C) substitution on neutral and charged SW-defected BN have
      also been studied. Our results indicate that the C substitution of B in BN is in
      favour of the formation of SW defects. Structural and electronic calculations
      show rich charge-dependent properties of C substitutions in SW-defected BN, thus
      our theoretical study is important for various applications in the design of BN
      nanostructure-based devices. 

PMID- 27030260
TI  - Beyond "One Size Fits All": Physician Nonverbal Adaptability to Patients' Need
      for Paternalism and Its Positive Consultation Outcomes.
AB  - In this study, we tested whether physicians' ability to adapt their nonverbal
      behavior to their patients' preferences for a paternalistic interaction style is
      related to positive consultation outcomes. We hypothesized that the more
      physicians adapt their nonverbal dominance behavior to match their patients'
      preferences for physician paternalism, the more positively the patients perceive
      the medical interaction. We assessed the actual nonverbal dominance behavior of
      32 general practitioners when interacting with two of their patients and compared
      it with each of their patients' preferences for paternalism to obtain a measure
      of adaptability. Additionally, we measured patient outcomes with a questionnaire
      assessing patient satisfaction, trust in the physician, and evaluation of
      physician competence. Results show that the more nonverbal dominance the
      physician shows toward the patient who prefers a more paternalistic physician, as
      compared to toward the patient who prefers a less paternalistic physician (i.e.,
      the more the physician shows nonverbal behavioral adaptability), the more
      positive the consultation outcomes are. This means that physicians' ability to
      adapt aspects of their nonverbal dominance behavior to their individual patients'
      preferences is related to better outcomes for patients. As this study shows, it
      is advantageous for patients when a physician behaves flexibly instead of showing
      the same behavior towards all patients. Physician training might want to focus
      more on teaching a diversity of different behavior repertoires instead of a given
      set of behaviors.

PMID- 27030261
TI  - Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78
      Complete Genome Sequences.
AB  - Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and
      laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic
      HPV vaccines. We established the largest collection of globally circulating HPV11
      isolates to date and examined the genomic diversity of 433 isolates and 78
      complete genomes (CGs) from six continents. The genomic variation within the
      2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207
      (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11
      variants containing unique single nucleotide polymorphisms (SNPs), indels
      (insertions or deletions), or amino acid changes were fully sequenced. A maximum
      likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our
      study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and
      four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific
      SNPs within the CG were identified, as well as the 208-bp representative region
      for CG-based phylogenetic clustering within the partial E2 open reading frame and
      noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by
      sublineages A1, A3, and A4 and lineage B. IMPORTANCE: This collaborative
      international study defined the global heterogeneity of HPV11 and established the
      largest collection of globally circulating HPV11 genomic variants to date. Thirty
      novel complete HPV11 genomes were determined and submitted to the available
      sequence repositories. Global phylogenetic analysis revealed two HPV11 variant
      lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the
      representative region identified within the partial genomic region E2/noncoding
      region 2 (NCR2) will enable the simpler identification and comparison of HPV11
      variants worldwide. This study provides an important knowledge base for HPV11 for
      future studies in HPV epidemiology, evolution, pathogenicity, prevention, and
      molecular assay development.

PMID- 27030262
TI  - B Cell Responses during Secondary Dengue Virus Infection Are Dominated by Highly
      Cross-Reactive, Memory-Derived Plasmablasts.
AB  - Dengue virus (DENV) infection results in the production of both type-specific and
      cross-neutralizing antibodies. While immunity to the infecting serotype is long
      lived, heterotypic immunity wanes a few months after infection. Epidemiological
      studies link secondary heterotypic infections with more severe symptoms, and
      cross-reactive, poorly neutralizing antibodies have been implicated in this
      increased disease severity. To understand the cellular and functional properties
      of the acute dengue virus B cell response and its role in protection and
      immunopathology, we characterized the plasmablast response in four secondary DENV
      type 2 (DENV2) patients. Dengue plasmablasts had high degrees of somatic
      hypermutation, with a clear preference for replacement mutations. Clonal
      expansions were also present in each donor, strongly supporting a memory origin
      for these acutely induced cells. We generated 53 monoclonal antibodies (MAbs)
      from sorted patient plasmablasts and found that DENV-reactive MAbs were largely
      envelope specific and cross neutralizing. Many more MAbs neutralized DENV than
      reacted to envelope protein, emphasizing the significance of virion-dependent B
      cell epitopes and the limitations of envelope protein-based antibody screening. A
      majority of DENV-reactive MAbs, irrespective of neutralization potency, enhanced
      infection by antibody-dependent enhancement (ADE). Interestingly, even though
      DENV2 was the infecting serotype in all four patients, several MAbs from two
      patients neutralized DENV1 more potently than DENV2. Further, half of all type
      specific neutralizing MAbs were also DENV1 biased in binding. Taken together,
      these findings are reminiscent of original antigenic sin (OAS), given that the
      patients had prior dengue virus exposures. These data describe the ongoing B cell
      response in secondary patients and may further our understanding of the impact of
      antibodies in dengue virus pathogenesis. IMPORTANCE: In addition to their role in
      protection, antibody responses have been hypothesized to contribute to the
      pathology of dengue. Recent studies characterizing memory B cell (MBC)-derived
      MAbs have provided valuable insight into the targets and functions of B cell
      responses generated after DENV exposure. However, in the case of secondary
      infections, such MBC-based approaches fail to distinguish acutely induced cells
      from the preexisting MBC pool. Our characterization of plasmablasts and
      plasmablast-derived MAbs provides a focused analysis of B cell responses
      activated during ongoing infection. Additionally, our studies provide evidence of
      OAS in the acute-phase dengue virus immune response, providing a basis for future
      work examining the impact of OAS phenotype antibodies on protective immunity and
      disease severity in secondary infections.

PMID- 27030263
TI  - Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a
      Receptor for Middle East Respiratory Syndrome Coronavirus.
AB  - The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS
      CoV) binds to its receptor, dipeptidyl peptidase 4 (DPP4), via 14 interacting
      amino acids. We previously showed that if the five interacting amino acids which
      differ between hamster and human DPP4 are changed to the residues found in human
      DPP4, hamster DPP4 does act as a receptor. Here, we show that the functionality
      of hamster DPP4 as a receptor is severely decreased if less than 4 out of 5 amino
      acids are changed. IMPORTANCE: The novel emerging coronavirus MERS-CoV has
      infected >1,600 people worldwide, and the case fatality rate is ~36%. In this
      study, we show that by changing 4 amino acids in hamster DPP4, this protein
      functions as a receptor for MERS-CoV. This work is vital in the development of
      new small-animal models, which will broaden our understanding of MERS-CoV and be
      instrumental in the development of countermeasures.

PMID- 27030264
TI  - A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and
      Prevents Corneal Immunopathology via Humoral Immunity.
AB  - Correlates of immunologic protection requisite for an efficacious herpes simplex
      virus 1 (HSV-1) vaccine remain unclear with respect to viral pathogenesis and
      clinical disease. In the present study, mice were vaccinated with a novel
      avirulent, live attenuated virus (0DeltaNLS) or an adjuvanted glycoprotein D
      subunit (gD-2) similar to that used in several human clinical trials. Mice
      vaccinated with 0DeltaNLS showed superior protection against early viral
      replication, neuroinvasion, latency, and mortality compared to that of gD-2
      vaccinated or naive mice following ocular challenge with a neurovirulent clinical
      isolate of HSV-1. Moreover, 0DeltaNLS-vaccinated mice exhibited protection
      against ocular immunopathology and maintained corneal mechanosensory function.
      Vaccinated mice also showed suppressed T cell activation in the draining lymph
      nodes following challenge. Vaccine efficacy correlated with serum neutralizing
      antibody titers. Humoral immunity was identified as the correlate of protection
      against corneal neovascularization, HSV-1 shedding, and latency through passive
      immunization. Overall, 0DeltaNLS affords remarkable protection against HSV-1
      associated ocular sequelae by impeding viral replication, dissemination, and
      establishment of latency. IMPORTANCE: HSV-1 manifests in a variety of clinical
      presentations ranging from a rather benign "cold sore" to more severe forms of
      infection, including necrotizing stromal keratitis and herpes simplex
      encephalitis. The present study was undertaken to evaluate a novel vaccine to
      ocular HSV-1 infection not only for resistance to viral replication and spread
      but also for maintenance of the visual axis. The results underscore the necessity
      to reconsider strategies that utilize attenuated live virus as opposed to subunit
      vaccines against ocular HSV-1 infection.

PMID- 27030265
TI  - The Human Papillomavirus 16 E7 Oncoprotein Attenuates AKT Signaling To Promote
      Internal Ribosome Entry Site-Dependent Translation and Expression of c-MYC.
AB  - While the role of high-risk human papillomavirus (HPV) oncoproteins E6 and E7 in
      targeting p53 and retinoblastoma (Rb) has been intensively studied, how E6 and E7
      manipulate cellular signaling cascades to promote the viral life cycle and cancer
      development is less understood. Keratinocytes containing the episomal HPV-16
      genome had decreased activation of AKT, which was phenocopied by HPV-16 E7
      expression alone. Attenuation of phosphorylated AKT (pAKT) by E7 was independent
      of the Rb degradation function of E7 but could be ablated by a missense mutation
      in the E7 carboxy terminus, H73E, thereby defining a novel structure-function
      phenotype for E7. Downstream of AKT, reduced phosphorylation of p70 S6K and 4E
      BP1 was also observed in E7-expressing keratinocytes, which coincided with an
      increase in internal ribosomal entry site (IRES)-dependent translation that
      enhanced the expression of several cellular proteins, including MYC, Bax, and the
      insulin receptor. The decrease in pAKT mediated by E7 is in contrast to the
      widely observed increase of pAKT in invasive cervical cancers, suggesting that
      the activation of AKT signaling could be acquired during the progression from
      initial productive infections to invasive carcinomas. IMPORTANCE: HPV causes
      invasive cervical cancers through the dysregulation of the cell cycle regulators
      p53 and Rb, which are degraded by the viral oncoproteins E6 and E7, respectively.
      Signaling cascades contribute to cancer progression and cellular differentiation,
      and how E6 and E7 manipulate those pathways remains unclear. The phosphoinositol
      3-kinase (PI3K)/AKT pathway regulates cellular processes, including
      proliferation, cell survival, and cell differentiation. Surprisingly, we found
      that HPV-16 decreased the phosphorylation of AKT (pAKT) and that this is a
      function of E7 that is independent of the Rb degradation function. This is in
      contrast to the observed increase in AKT signaling in nearly 80% of cervical
      cancers, which typically show an acquired mutation within the PI3K/AKT cascade
      leading to constitutive activation of the pathway. Our observations suggest that
      multiple changes in the activation and effects of AKT signaling occur in the
      progression from productive HPV infections to invasive cervical cancers.

PMID- 27030266
TI  - Roles of Us8A and Its Phosphorylation Mediated by Us3 in Herpes Simplex Virus 1
      Pathogenesis.
AB  - The herpes simplex virus 1 (HSV-1) Us8A gene overlaps the gene that encodes
      glycoprotein E (gE). Previous studies have investigated the roles of Us8A in HSV
      1 infection using null mutations in Us8A and gE; therefore, the role of Us8A
      remains to be elucidated. In this study, we investigated the function of Us8A and
      its phosphorylation at serine 61 (Ser-61), which we recently identified as a
      phosphorylation site by mass spectrometry-based phosphoproteomic analysis of HSV
      1-infected cells, in HSV-1 pathogenesis. We observed that (i) the phosphorylation
      of Us8A Ser-61 in infected cells was dependent on the activity of the virus
      encoded Us3 protein kinase; (ii) the Us8A null mutant virus exhibited a 10-fold
      increase in the 50% lethal dose for virulence in the central nervous system (CNS)
      of mice following intracranial infection compared with a repaired virus; (iii)
      replacement of Ser-61 with alanine (S61A) in Us8A had little effect on virulence
      in the CNS of mice following intracranial infection, whereas it significantly
      reduced the mortality of mice following ocular infection to levels similar to the
      Us8A null mutant virus; (iv) the Us8A S61A mutation also significantly reduced
      viral yields in mice following ocular infection, mainly in the trigeminal ganglia
      and brains; and (v) a phosphomimetic mutation at Us8A Ser-61 restored wild-type
      viral yields and virulence. Collectively, these results indicate that Us8A is a
      novel HSV-1 virulence factor and suggest that the Us3-mediated phosphorylation of
      Us8A Ser-61 regulates Us8A function for viral invasion into the CNS from
      peripheral sites. IMPORTANCE: The DNA genomes of viruses within the subfamily
      Alphaherpesvirinae are divided into unique long (UL) and unique short (Us)
      regions. Us regions contain alphaherpesvirus-specific genes. Recently, high
      throughput sequencing of ocular isolates of HSV-1 showed that Us8A was the most
      highly conserved of 13 herpes simplex virus 1 (HSV-1) genes mapped to the Us
      region, suggesting Us8A may have an important role in the HSV-1 life cycle.
      However, the specific role of Us8A in HSV-1 infection remains to be elucidated.
      Here, we show that Us8A is a virulence factor for HSV-1 infection in mice, and
      the function of Us8A for viral invasion into the central nervous system from
      peripheral sites is regulated by Us3-mediated phosphorylation of the protein at
      Ser-61. This is the first study to report the significance of Us8A and its
      regulation in HSV-1 infection.

PMID- 27030267
TI  - The Coxsackievirus and Adenovirus Receptor: Glycosylation and the Extracellular
      D2 Domain Are Not Required for Coxsackievirus B3 Infection.
AB  - The coxsackievirus and adenovirus receptor (CAR) is a member of the
      immunoglobulin superfamily (IgSF) and functions as a receptor for coxsackie B
      viruses (CVBs). The extracellular portion of CAR comprises two glycosylated
      immunoglobulin-like domains, D1 and D2. CAR-D1 binds to the virus and is
      essential for virus infection; however, it is not known whether D2 is also
      important for infection, and the role of glycosylation has not been explored. To
      understand the function of these structural components in CAR-mediated CVB3
      infection, we generated a panel of human (h) CAR deletion and substitution
      mutants and analyzed their functionality as CVB receptors, examining both virus
      binding and replication. Lack of glycosylation of the CAR-D1 or -D2 domains did
      not adversely affect CVB3 binding or infection, indicating that the glycosylation
      of CAR is not required for its receptor functions. Deletion of the D2 domain
      reduced CVB3 binding, with a proportionate reduction in the efficiency of virus
      infection. Replacement of D2 with the homologous D2 domain from chicken CAR, or
      with the heterologous type C2 immunoglobulin-like domain from IgSF11, another
      IgSF member, fully restored receptor function; however, replacement of CAR-D2
      with domains from CD155 or CD80 restored function only in part. These data
      indicate that glycosylation of the extracellular domain of hCAR plays no role in
      CVB3 receptor function and that CAR-D2 is not specifically required. The D2
      domain may function largely as a spacer permitting virus access to D1; however,
      the data may also suggest that D2 affects virus binding by influencing the
      conformation of D1. IMPORTANCE: An important step in virus infection is the
      initial interaction of the virus with its cellular receptor. Although the role in
      infection of the extracellular CAR-D1, cytoplasmic, and transmembrane domains
      have been analyzed extensively, nothing is known about the function of CAR-D2 and
      the extracellular glycosylation of CAR. Our data indicate that glycosylation of
      the extracellular CAR domain has only minor importance for the function of CAR as
      CVB3 receptor and that the D2 domain is not essential per se but contributes to
      receptor function by promoting the exposure of the D1 domain on the cell surface.
      These results contribute to our understanding of the coxsackievirus-receptor
      interactions.

PMID- 27030268
TI  - Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in
      China.
AB  - Due to enzootic infections in poultry and persistent human infections in China,
      influenza A (H7N9) virus has remained a public health threat. The Yangtze River
      Delta region, which is located in eastern China, is well recognized as the
      original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9
      viruses from all three outbreak waves since 2013, we identified the Pearl River
      Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly
      introduced from these two sources to the other areas, and the persistent
      circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves.
      Poultry movements may contribute to the geographic expansion of the virus. In
      addition, the AnH1 genotype, which was predominant during wave 1, was replaced by
      JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of
      a new source and the continuous evolution of the virus hamper the elimination of
      H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans.
      Therefore, both surveillance of H7N9 viruses in humans and poultry and
      supervision of poultry movements should be strengthened. IMPORTANCE: Since its
      occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have
      been demonstrating the continuing pandemic threat posed by the current influenza
      ecosystem in China. As the viruses are silently circulated in poultry, with
      potentially severe outcomes in humans, H7N9 virus activity in humans in China is
      very important to understand. In this study, we identified a newly emerged H7N9
      outbreak source in the Pearl River Delta region. Both sources in the Yangtze
      River Delta region and the Pearl River Delta region have been established and
      found to be responsible for the H7N9 outbreaks in mainland China.

PMID- 27030269
TI  - Trimer Enhancement Mutation Effects on HIV-1 Matrix Protein Binding Activities.
AB  - The HIV-1 matrix (MA) protein is the amino-terminal domain of the HIV-1 precursor
      Gag (Pr55Gag) protein. MA binds to membranes and RNAs, helps transport Pr55Gag
      proteins to virus assembly sites at the plasma membranes of infected cells, and
      facilitates the incorporation of HIV-1 envelope (Env) proteins into virions by
      virtue of an interaction with the Env protein cytoplasmic tails (CTs). MA has
      been shown to crystallize as a trimer and to organize on membranes in hexamer
      lattices. MA mutations that localize to residues near the ends of trimer spokes
      have been observed to impair Env protein assembly into virus particles, and
      several of these are suppressed by the 62QR mutation at the hubs of trimer
      interfaces. We have examined the binding activities of wild-type (WT) MA and 62QR
      MA variants and found that the 62QR mutation stabilized MA trimers but did not
      alter the way MA proteins organized on membranes. Relative to WT MA, the 62QR
      protein showed small effects on membrane and RNA binding. However, 62QR proteins
      bound significantly better to Env CTs than their WT counterparts, and CT binding
      efficiencies correlated with trimerization efficiencies. Our data suggest a model
      in which multivalent binding of trimeric HIV-1 Env proteins to MA trimers
      contributes to the process of Env virion incorporation. IMPORTANCE: The HIV-1 Env
      proteins assemble as trimers, and incorporation of the proteins into virus
      particles requires an interaction of Env CT domains with the MA domains of the
      viral precursor Gag proteins. Despite this knowledge, little is known about the
      mechanisms by which MA facilitates the virion incorporation of Env proteins. To
      help elucidate this process, we examined the binding activities of an MA mutant
      that stabilizes MA trimers. We found that the mutant proteins organized similarly
      to WT proteins on membranes, and that mutant and WT proteins revealed only slight
      differences in their binding to RNAs or lipids. However, the mutant proteins
      showed better binding to Env CTs than the WT proteins, and CT binding correlated
      with MA trimerization. Our results suggest that multivalent binding of trimeric
      HIV-1 Env proteins to MA trimers contributes to the process of Env virion
      incorporation.

PMID- 27030270
TI  - Pathogenesis of Influenza D Virus in Cattle.
AB  - Cattle have been proposed as the natural reservoir of a novel member of the virus
      family Orthomyxoviridae, which has been tentatively classified as influenza D
      virus (IDV). Although isolated from sick animals, it is unclear whether IDV
      causes any clinical disease in cattle. To address this aspect of Koch's
      postulates, three dairy calves (treatment animals) held in individual pens were
      inoculated intranasally with IDV strain D/bovine/Mississippi/C00046N/2014. At 1
      day postinoculation, a seronegative calf (contact animal) was added to each of
      the treatment animal pens. The cattle in both treatment and contact groups
      seroconverted, and virus was detected in their respiratory tracts.
      Histologically, there was a significant increase in neutrophil tracking in
      tracheal epithelia of the treatment calves compared to control animals. While
      infected and contact animals demonstrated various symptoms of respiratory tract
      infection, they were mild, and the calves in the treatment group did not differ
      from the controls in terms of heart rate, respiratory rate, or rectal
      temperature. To mimic zoonotic transmission, two ferrets were exposed to a
      plastic toy fomite soaked with infected nasal discharge from the treatment
      calves. These ferrets did not shed the virus or seroconvert. In summary, this
      study demonstrates that IDV causes a mild respiratory disease upon experimental
      infection of cattle and can be transmitted effectively among cattle by in-pen
      contact, but not from cattle to ferrets through fomite exposure. These findings
      support the hypothesis that cattle are a natural reservoir for the virus.
      IMPORTANCE: A novel influenza virus, tentatively classified as influenza D virus
      (IDV), was identified in swine, cattle, sheep, and goats. Among these hosts,
      cattle have been proposed as the natural reservoir. In this study, we show that
      cattle experimentally infected with IDV can shed virus and transmit it to other
      cattle through direct contact, but not to ferrets through fomite routes. IDV
      caused minor clinical signs in the infected cattle, fulfilling another of Koch's
      postulates for this novel agent, although other objective clinical endpoints were
      not different from those of control animals. Although the disease observed was
      mild, IDV induced neutrophil tracking and epithelial attenuation in cattle
      trachea, which could facilitate coinfection with other pathogens, and in doing
      so, predispose animals to bovine respiratory disease.

PMID- 27030271
TI  - Differential Inductions of RNA Silencing among Encapsidated Double-Stranded RNA
      Mycoviruses in the White Root Rot Fungus Rosellinia necatrix.
AB  - RNA silencing acts as a defense mechanism against virus infection in a wide
      variety of organisms. Here, we investigated inductions of RNA silencing against
      encapsidated double-stranded RNA (dsRNA) fungal viruses (mycoviruses), including
      a partitivirus (RnPV1), a quadrivirus (RnQV1), a victorivirus (RnVV1), a
      mycoreovirus (RnMyRV3), and a megabirnavirus (RnMBV1) in the phytopathogenic
      fungus Rosellinia necatrix Expression profiling of RNA silencing-related genes
      revealed that a dicer-like gene, an Argonaute-like gene, and two RNA-dependent
      RNA polymerase genes were upregulated by RnMyRV3 or RnMBV1 infection but not by
      other virus infections or by constitutive expression of dsRNA in R. necatrix
      Massive analysis of viral small RNAs (vsRNAs) from the five mycoviruses showed
      that 19- to 22-nucleotide (nt) vsRNAs were predominant; however, their ability to
      form duplexes with 3' overhangs and the 5' nucleotide preferences of vsRNAs
      differed among the five mycoviruses. The abundances of 19- to 22-nt vsRNAs from
      RnPV1, RnQV1, RnVV1, RnMyRV3, and RnMBV1 were 6.8%, 1.2%, 0.3%, 13.0%, and 24.9%,
      respectively. Importantly, the vsRNA abundances and accumulation levels of viral
      RNA were not always correlated, and the origins of the vsRNAs were
      distinguishable among the five mycoviruses. These data corroborated diverse
      interactions between encapsidated dsRNA mycoviruses and RNA silencing. Moreover,
      a green fluorescent protein (GFP)-based sensor assay in R. necatrix revealed that
      RnMBV1 infection induced silencing of the target sensor gene (GFP gene and the
      partial RnMBV1 sequence), suggesting that vsRNAs from RnMBV1 activated the RNA
      induced silencing complex. Overall, this study provides insights into RNA
      silencing against encapsidated dsRNA mycoviruses. IMPORTANCE: Encapsidated dsRNA
      fungal viruses (mycoviruses) are believed to replicate inside their virions;
      therefore, there is a question of whether they induce RNA silencing. Here, we
      investigated inductions of RNA silencing against encapsidated dsRNA mycoviruses
      (a partitivirus, a quadrivirus, a victorivirus, a mycoreovirus, and a
      megabirnavirus) in Rosellinia necatrix We revealed upregulation of RNA silencing
      related genes in R. necatrix infected with a mycoreovirus or a megabirnavirus but
      not with other viruses, which was consistent with the relatively high abundances
      of vsRNAs from the two mycoviruses. We also showed common and different molecular
      features and origins of the vsRNAs from the five mycoviruses. Furthermore, we
      demonstrated the activation of RNA-induced silencing complex by mycoviruses in R.
      necatrix Taken together, our data provide insights into an RNA silencing pathway
      against encapsidated dsRNA mycoviruses which is differentially induced among
      encapsidated dsRNA mycoviruses; that is, diverse replication strategies exist
      among encapsidated dsRNA mycoviruses.

PMID- 27030272
TI  - Quantitation of Productively Infected Monocytes and Macrophages of Simian
      Immunodeficiency Virus-Infected Macaques.
AB  - Despite the success of combined antiretroviral therapy (ART), human
      immunodeficiency virus (HIV) infection remains a lifelong infection because of
      latent viral reservoirs in infected patients. The contribution of CD4(+) T cells
      to infection and disease progression has been extensively studied. However,
      during early HIV infection, macrophages in brain and other tissues are infected
      and contribute to tissue-specific diseases, such as encephalitis and dementia in
      brain and pneumonia in lung. The extent of infection of monocytes and macrophages
      has not been rigorously assessed with assays comparable to those used to study
      infection of CD4(+) T cells and to evaluate the number of CD4(+) T cells that
      harbor infectious viral genomes. To assess the contribution of productively
      infected monocytes and macrophages to HIV- and simian immunodeficiency virus
      (SIV)-infected cells in vivo, we developed a quantitative virus outgrowth assay
      (QVOA) based on similar assays used to quantitate CD4(+) T cell latent reservoirs
      in HIV- and SIV-infected individuals in whom the infection is suppressed by ART.
      Myeloid cells expressing CD11b were serially diluted and cocultured with
      susceptible cells to amplify virus. T cell receptor beta RNA was measured as a
      control to assess the potential contribution of CD4(+) T cells in the assay.
      Virus production in the supernatant was quantitated by quantitative reverse
      transcription-PCR. Productively infected myeloid cells were detected in blood,
      bronchoalveolar lavage fluid, lungs, spleen, and brain, demonstrating that these
      cells persist throughout SIV infection and have the potential to contribute to
      the viral reservoir during ART. IMPORTANCE: Infection of CD4(+) T cells and their
      role as latent reservoirs have been rigorously assessed; however, the frequency
      of productively infected monocytes and macrophages in vivo has not been similarly
      studied. Myeloid cells, unlike lymphocytes, are resistant to the cytopathic
      effects of HIV. Moreover, tissue-resident macrophages have the ability to self
      renew and persist in the body for months to years. Thus, tissue macrophages, once
      infected, have the characteristics of a potentially stable viral reservoir. A
      better understanding of the number of productively infected macrophages is
      crucial to further evaluate the role of infected myeloid cells as a potential
      viral reservoir. In the study described here we compared the frequency of
      productively infected CD4(+) T cells and macrophages in an SIV-infected macaque
      model. We developed a critical assay that will allow us to quantitate myeloid
      cells containing viral genomes that lead to productive infection in SIV-infected
      macaques and assess the role of macrophages as potential reservoirs.

PMID- 27030273
TI  - Identification of the Fusion Peptide-Containing Region in Betacoronavirus Spike
      Glycoproteins.
AB  - The fusion peptides (FP) play an essential role in fusion of viral envelope with
      cellular membranes. The location and properties of the FPs in the spike (S)
      glycoproteins of different coronaviruses (CoV) have not yet been determined.
      Through amino acid sequence analysis of S proteins of representative CoVs, we
      identified a common region as a possible FP (pFP) that shares the characteristics
      of FPs of class I viral fusion proteins, including high Ala/Gly content,
      intermediate hydrophobicity, and few charged residues. To test the hypothesis
      that this region contains the CoV FP, we systemically mutated every residue in
      the pFP of Middle East respiratory syndrome betacoronavirus (MERS-CoV) and found
      that 11 of the 22 residues in the pFP (from G953 to L964, except for A956) were
      essential for S protein-mediated cell-cell fusion and virus entry. The synthetic
      MERS-CoV pFP core peptide (955IAGVGWTAGL964) induced extensive fusion of liposome
      membranes, while mutant peptide failed to induce any lipid mixing. We also
      selectively mutated residues in pFPs of two other beta-CoVs, severe acute
      respiratory syndrome coronavirus (SARS-CoV) and mouse hepatitis virus (MHV).
      Although the amino acid sequences of these two pFPs differed significantly from
      that of MERS-CoV and each other, most of the pFP mutants of SARS-CoV and MHV also
      failed to mediate membrane fusion, suggesting that these pFPs are also the
      functional FPs. Thus, the FPs of 3 different lineages of beta-CoVs are conserved
      in location within the S glycoproteins and in their functions, although their
      amino acid sequences have diverged significantly during CoV evolution.
      IMPORTANCE: Within the class I viral fusion proteins of many enveloped viruses,
      the FP is the critical mediator of fusion of the viral envelope with host cell
      membranes leading to virus infection. FPs from within a virus family, like
      influenza viruses or human immunodeficiency viruses (HIV), tend to share high
      amino acid sequence identity. In this study, we determined the location and amino
      acid sequences of the FPs of S glycoproteins of 3 beta-CoVs, MERS-CoV, SARS-CoV,
      and MHV, and demonstrated that they were essential for mediating cell-cell fusion
      and virus entry. Interestingly, in marked contrast to the FPs of influenza and
      HIV, the primary amino acid sequences of the FPs of beta-CoVs in 3 different
      lineages differed significantly. Thus, during evolution the FPs of beta-CoVs have
      diverged significantly in their primary sequences while maintaining the same
      essential biological functions. Our findings identify a potential new target for
      development of drugs against CoVs.

PMID- 27030274
TI  - Short Intracellular HIV-1 Transcripts as Biomarkers of Residual Immune Activation
      in Patients on Antiretroviral Therapy.
AB  - HIV-1 patients continue to remain at an abnormal immune status despite prolonged
      combination antiretroviral therapy (cART), which results in an increased risk of
      non-AIDS-related diseases. Given the growing recognition of the importance of
      understanding and controlling the residual virus in patients, additional
      virological markers to monitor infected cells are required. However, viral
      replication in circulating cells is much poorer than that in lymph nodes, which
      results in the absence of markers to distinguish these cells from uninfected
      cells in the blood. In this study, we identified prematurely terminated short HIV
      1 transcripts (STs) in peripheral blood mononuclear cells (PBMCs) as an efficient
      intracellular biomarker to monitor viral activation and immune status in patients
      with cART-mediated full viral suppression in plasma. STs were detected in PBMCs
      obtained from both treated and untreated patients. ST levels in untreated
      patients generally increased with disease progression and decreased after
      treatment initiation. However, some patients exhibited sustained high levels of
      ST and low CD4(+) cell counts despite full viral suppression by treatment. The
      levels of STs strongly reflected chronic immune activation defined by
      coexpression of HLA-DR and CD38 on CD8(+) T cells, rather than circulating
      proviral load. These observations represent evidence for a relationship between
      viral persistence and host immune activation, which in turn results in the
      suboptimal increase in CD4(+) cells despite suppressive antiretroviral therapy.
      This cell-based measurement of viral persistence contributes to an improved
      understanding of the dynamics of viral persistence in cART patients and will
      guide therapeutic approaches targeting viral reservoirs. IMPORTANCE: Combination
      antiretroviral therapy (cART) suppresses HIV-1 load to below the detectable limit
      in plasma. However, the virus persists, and patients remain at an abnormal immune
      status, which results in an increased risk of non-AIDS-related complications. To
      achieve a functional cure for HIV-1 infection, activities of viral reservoirs
      must be quantified and monitored. However, latently infected cells are difficult
      to be monitored. Here, we identified prematurely terminated short HIV-1
      transcripts (STs) as an efficient biomarker for monitoring viral activation and
      immune status in patients with cART-mediated full viral suppression in plasma.
      This cell-based measurement of viral persistence will contribute to our
      understanding of the impact of residual virus on chronic immune activation in HIV
      1 patients during cART.

PMID- 27030275
TI  - Structural and Functional Consequences of Three Cancer-Associated Mutations of
      the Oncogenic Phosphatase SHP2.
AB  - The proto-oncogene PTPN11 encodes a cytoplasmic protein tyrosine phosphatase,
      SHP2, which is required for normal development and sustained activation of the
      Ras-MAPK signaling pathway. Germline mutations in SHP2 cause developmental
      disorders, and somatic mutations have been identified in childhood and adult
      cancers and drive leukemia in mice. Despite our knowledge of the PTPN11
      variations associated with pathology, the structural and functional consequences
      of many disease-associated mutants remain poorly understood. Here, we combine X
      ray crystallography, small-angle X-ray scattering, and biochemistry to elucidate
      structural and mechanistic features of three cancer-associated SHP2 variants
      harboring single point mutations within the N-SH2:PTP interdomain autoinhibitory
      interface. Our findings directly compare the impact of each mutation on
      autoinhibition of the phosphatase and advance the development of structure-guided
      and mutation-specific SHP2 therapies.

PMID- 27030276
TI  - UK Neovascular Age-Related Macular Degeneration Database. Report 6: time to
      retreatment after a pause in therapy. Outcomes from 92 976 intravitreal
      ranibizumab injections.
AB  - BACKGROUND/AIMS: To study the time to retreatment in eyes with neovascular age
      related macular degeneration (nAMD) that had been treatment-free for intervals of
      3 months, 6 months, 9 months and 12 months during the maintenance phase of
      ranibizumab therapy within the UK National Health Service. METHODS: In this
      multicentre national nAMD database study, structured data were collected from 14
      centres (involving 12 951 eyes receiving 92 976 ranibizumab injections). Patients
      were treated with three fixed, monthly injections in a loading phase of
      treatment, followed by a pro re nata retreatment regimen in a maintenance phase.
      Eyes with a treatment-free interval (TFI) of 3 months, 6 months, 9 months or 12
      months in the maintenance phase were identified and the time to retreatment after
      these TFIs was determined. RESULTS: The time to retreatment for the 20th and 50th
      centiles was 0.58/2.54 months after a 3-month TFI, 2.07/9.62 months after a 6
      month TFI, 3.69/15.84 months after a 9-month TFI and 5.90/22.49 months after a 12
      month TFI. Following a TFI of 3 months, 6 months, 9 months and 12 months, 68%,
      44%, 31% and 21% of eyes required retreatments after an additional 6 months of
      follow-up, respectively. Similarly, after 12 months of follow-up, 77%, 56%, 43%
      and 34% of these eyes required retreatment. CONCLUSIONS: This study provides
      times to retreatment in eyes with nAMD that have been treatment-free for
      intervals of 3-12 months and demonstrates the likelihood of repeat therapy within
      the next year, even after a TFI of 12 months. These outcomes can help plan
      appropriate follow-up intervals for patients who have been treatment-free for
      intervals of up to 12 months.

PMID- 27030277
TI  - Three-month outcome of ziv-aflibercept for exudative age-related macular
      degeneration.
AB  - PURPOSE: In vitro and in vivo studies did not detect toxicity to the retinal
      pigment epithelium cells using intravitreal ziv-aflibercept. Our purpose is to
      ascertain the 3-month safety and efficacy in wet age-related macular degeneration
      (AMD) treated with intravitreal ziv-aflibercept. METHODS: Prospectively,
      consecutive patients with wet AMD underwent ziv-aflibercept intravitreal
      injection (1.25 mg/0.05 mL) from March 2015 to November 2015. Monitoring of best
      corrected visual acuity, intraocular inflammation, cataract progression and by
      spectral domain optical coherence tomography were carried out at baseline day 1,
      1 week, 1 month, 2 months and 3 months after injections. RESULTS: 30 eyes were
      treated (22 Caucasians, 8 Indians; 16 men, 14 women; 14 right eyes and 16 left
      eyes) with mean age of 74.3 years with 11 treatment-naive cases and 19 having had
      treatment-non-naive. Best-corrected visual acuity improved from baseline logMAR
      1.08-0.74 at 1 week, 0.72 at 1 month, 0.67 at 2 months and 0.71 at 3 months
      (p<0.001 for all time periods). Central macular thickness in microns decreased
      from 332.8 to 302.0 at 1 week, 244.8 at 1 month, 229.0 at 2 months and 208.2 at 3
      months (p<0.001 for all time periods). There were no signs of intraocular
      inflammation, or change in lens status or increase in intraocular pressure
      throughout the study. CONCLUSIONS: Off label use of ziv-aflibercept improves
      visual acuity, without detectable ocular toxicity and offers a cheaper
      alternative to the same molecule aflibercept, especially in low/middle-income
      countries and in countries where aflibercept (Eylea) is not available. TRIAL
      REGISTRATION NUMBER: NCT02486484.

PMID- 27030278
TI  - Paediatric infectious keratitis at tertiary referral centres in Vancouver,
      Canada.
AB  - OBJECTIVE: To report the clinical and microbiological profiles of paediatric
      patients with infectious keratitis in Vancouver, Canada. DESIGN: In this
      observational case series, the microbiology results and medical records of 17
      eyes with microbial keratitis in 16 children aged 17 years or younger were
      retrospectively reviewed. These patients had undergone corneal scraping between
      May 2006 and April 2011 at BC Children's Hospital or Vancouver General Hospital
      Eye Care Centre in Vancouver, British Columbia, Canada. Demographic information,
      clinical features, predisposing factors, results of microbiology studies,
      antibiotic susceptibilities, treatment course and outcomes were analysed.
      RESULTS: The mean age of patients was 11+/-5.7 years (range 1-17 years) and the
      male:female ratio was 1.4:1. Major predisposing factors were contact lens wear
      (6/17; 35%), and pre-existing ocular surface conditions including blepharitis
      (3/17; 18%) and Stevens-Johnson syndrome (3/17; 18%). Four patients had a
      previous corneal ulcer. The most commonly isolated microorganisms were
      Staphylococcus epidermidis and Acanthamoeba. Acanthamoeba was isolated in 67% of
      contact lens-related corneal ulcers, while the remaining 33% of contact lens
      related corneal ulcers were associated with infection with Pseudomonas
      aeruginosa. Final visual acuity was better than 20/60 in 9 out of 16 patients
      (56%). Three patients subsequently required surgical management with either
      penetrating keratoplasty or deep anterior lamellar keratoplasty for treatment of
      corneal scarring. CONCLUSIONS: Contact lens wear and pre-existing ocular surface
      conditions are significant risk factors for the development of infectious
      keratitis in our paediatric population. Knowledge of regional patterns of
      infection and susceptibility are essential in ensuring prompt treatment of this
      potentially sight-threatening condition.

PMID- 27030280
TI  - Relationship between high serum ferritin level and glaucoma in a South Korean
      population: the Kangbuk Samsung health study.
AB  - BACKGROUND/AIMS: To investigate the association between serum ferritin levels and
      glaucoma in a South Korean population. METHODS: This retrospective cross
      sectional study included 164 029 subjects who underwent screening at Kangbuk
      Samsung Hospital Health Screening Center between August 2012 and July 2013. All
      subjects underwent a physical examination, answered sociodemographic and
      behavioural questions, and provided samples for laboratory analyses. A digital
      fundus photograph of both eyes was taken, and all photographs were reviewed by
      ophthalmologists. The ophthalmologists determined if an eye had glaucoma based on
      criteria set forth by the International Society of Geographical and
      Epidemiological Ophthalmology and the appearance of the retinal nerve fibre layer
      and optic disc. RESULTS: The mean serum ferritin level was 56.98 ng/mL in women
      and 223.82 ng/mL in men. After adjusting for age, serum iron, total iron-binding
      capacity (TIBC), transferrin saturation, white blood cell (WBC) count, high
      sensitivity C-reactive protein (HsCRP) and total vitamin D level, males in the
      highest quartile for serum ferritin level had a higher OR for glaucoma than males
      in the lowest quartile (OR=1.176, 95% CI 1.030 to 1.342, p=0.016); we did not
      observe this relationship among women. Other markers of iron metabolism, such as
      iron level, transferrin saturation and TIBC, and inflammation measures, including
      WBC, HsCRP and total vitamin D, were not associated with glaucoma. CONCLUSIONS:
      High serum ferritin level was associated with a high risk of glaucoma in men, but
      not in women. Because serum ferritin is related to oxidative stress and
      inflammation, it might play a role in glaucoma development.

PMID- 27030279
TI  - Key drivers of visual acuity gains in neovascular age-related macular
      degeneration in real life: findings from the AURA study.
AB  - BACKGROUND/AIMS: To identify predictive markers for the outcomes of anti-vascular
      endothelial growth factor therapy for neovascular age-related macular
      degeneration (nAMD). METHODS: AURA was a retrospective, observational,
      multicentre study that monitored the 2-year outcomes following intravitreal
      ranibizumab treatment in patients with nAMD. Using stepwise regression analysis,
      we evaluated the association between visual acuity outcomes, baseline
      characteristics and resource utilisation in order to determine which variables
      are significantly linked to outcomes in AURA. We also examined the relationship
      between visual acuity outcomes and number of injections received. RESULTS:
      Analyses were performed using data from year 1 (n=1695) and year 2 completers
      (n=1184). Logistic analysis showed that baseline visual acuity score, age at
      start of therapy, number of ophthalmoscopies and optical coherence tomography
      (OCT) (combined) and number of injections (ranibizumab) were significant (p<0.05)
      prognostic factors for vision maintenance (loss <15 letters) or vision gain (>=15
      letters). Patients who received >7 injections (in 1 year) or >14 injections (over
      2 years) gained more letters and demonstrated greater vision maintenance (loss of
      <15 letters) than patients who received fewer injections. There was a significant
      (p<0.05) association between number of injections and national reimbursement
      schemes and OCT. CONCLUSIONS: A number of factors that are predictive of
      treatment outcomes in a real-life setting were identified. Notably, the decline
      of treatment benefits may be linked to number of injections and a failure to
      visit clinicians and receive OCT as required. These findings may be helpful in
      guiding ophthalmologist treatment decisions under limited time and financial
      constraints. TRIAL REGISTRATION NUMBER: NCT01447043.

PMID- 27030281
TI  - Influence of baseline demographic and clinical characteristics in the visual
      outcome of intermediate uveitis: a survival analysis.
AB  - BACKGROUND/AIMS: To describe in patients diagnosed with intermediate uveitis (IU)
      the incidence rate (IR) of visual loss and newly diagnosed clinical complications
      during follow-up. Also, to analyse the influence of baseline complications on
      visual loss. METHODS: Longitudinal retrospective cohort study which included 97
      affected eyes of 67 consecutive patients diagnosed with IU according to the
      Standardization of Uveitis Nomenclature group, first seen in our clinic between
      1986 and 2014, and until loss to follow-up, or 1 January 2015. Kaplan-Meier
      curves were set to account for temporary and permanent visual loss and
      development of clinical complications during follow-up. Cox's bivariate and
      multivariate regression models were constructed to examine the risk factors for
      visual loss. RESULTS: IRs (in events per 100 eyes-year) for the development of
      cystic macular oedema (CMO), epiretinal membrane (ERM) and cataracts were 5.9
      (3.70-9.4), 1.2 (0.50-2.6) and 6.6 (4.4-10.1), respectively. IRs per 100 eyes
      year of temporary moderate and severe visual loss episodes were 43.8 (37.3-51.4)
      and 6.4 (4.5-9.0), respectively. IR of permanent moderate visual loss was 5.3
      (3.3-8.3). After 2 years of follow-up, 21% of eyes had developed a permanent
      moderate visual loss. Presence at baseline of lower visual acuity was associated
      with higher IR of temporary visual loss episodes, and CMO was associated with
      higher IR of temporary moderate visual loss. CONCLUSIONS: IU seems to have a
      favourable long-term prognosis. Permanent visual loss occurs during the first
      year of the disease. Baseline characteristics could identify patients with a
      higher risk of poor visual prognosis.

PMID- 27030282
TI  - Atomic structure and surface defects at mineral-water interfaces probed by in
      situ atomic force microscopy.
AB  - Atomic scale details of surface structure play a crucial role for solid-liquid
      interfaces. While macroscopic characterization techniques provide averaged
      information about bulk and interfaces, high resolution real space imaging reveals
      unique insights into the role of defects that are believed to dominate many
      aspects of surface chemistry and physics. Here, we use high resolution dynamic
      Atomic Force Microscopy (AFM) to visualize and characterize in ambient water the
      morphology and atomic scale structure of a variety of nanoparticles of common
      clay minerals adsorbed to flat solid surfaces. Atomically resolved images of the
      (001) basal planes are obtained on all materials investigated, namely gibbsite,
      kaolinite, illite, and Na-montmorillonite of both natural and synthetic origin.
      Next to regions of perfect crystallinity, we routinely observe extended regions
      of various types of defects on the surfaces, including vacancies of one or few
      atoms, vacancy islands, atomic steps, apparently disordered regions, as well as
      strongly adsorbed seemingly organic and inorganic species. While their exact
      nature is frequently difficult to identify, our observations clearly highlight
      the ubiquity of such defects and their relevance for the overall physical and
      chemical properties of clay nanoparticle-water interfaces. 

PMID- 27030283
TI  - A comparison between indirect and objective wear-time assessment of removable
      orthodontic appliances.
AB  - Background/Objectives: Patients do not always adhere to the wear times prescribed
      for removable orthodontic appliances. We evaluated the validity and usability of
      indirect wear-time assessment methods by comparing wear-time estimates with
      microelectronically measured wear times in patients with removable orthodontic
      appliances. Methods: Wear times of 33 expansion plates, 34 functional appliances,
      and 42 retention plates of patients aged 6-20 years (12.3+/-2.9 years, 50.5%
      female) were indirectly determined by practitioners using a questionnaire
      assessing five parameters on a 5-point Likert scale: appliance handling,
      appliance appearance, bite shift, tooth movement, and appliance fit. The
      perceived difficulty in assessing each parameter was rated. Actual wear times
      were evaluated with microelectronic sensors in the appliances. Results:
      Regression analyses revealed that practitioners' decisions about wear times
      varied depending on the type of appliance and criteria used, with only one
      standard criterion best predicting estimated wear time for each appliance.
      Different standard criteria were better predictors of measured wear time: 22.3%
      of wear-time variability was explained by expansion plate appearance, 31.2% by
      functional appliance handling, and 18.8% by retainer fitting. However,
      practitioners rated the difficulty of assessment in most cases as 'easy'.
      Limitations: The study was not double blinded for technical reasons, and
      practitioners may have considered the evaluation criteria more carefully than in
      normal daily practice. Conclusions: Practitioners' decisions about wear times
      based on standard criteria strongly vary depending on the type of appliance and
      criteria used.

PMID- 27030284
TI  - Management of post-orthodontic white spot lesions: an updated systematic review.
AB  - Background/objectives: The management of post-orthodontic white spot lesions is
      based on remineralization strategies or a minimal-invasive camouflage of the
      lesions. Aim: The aim of this systematic review was to identify and assess the
      quality of evidence for the various clinical technologies. Search methods: Four
      databases were searched for relevant literature published in English between 2011
      and 31 October 2015 according to a pre-determined PICO. Only controlled clinical
      studies were considered. Abstract lists and the selected full-text papers were
      independently examined by two reviewers and any differences were solved in
      consensus. The Cochrane handbook and the AMSTAR tool were used for grading the
      risk of bias. The quality of evidence was rated according to GRADE. Results: Out
      of 280 identified publications, seven studies on remineralization, micro-abrasion
      and resin infiltration met the inclusion criteria. Two of them were assessed with
      low risk of bias. No pooling of results was possible due to study heterogeneity.
      The quality of evidence for all technologies was graded as very low. Limitations:
      Only papers published in English with more than 20 adolescents or young adults
      were considered. Furthermore, a follow-up period of at least 8 weeks was
      required. The publication bias could not be assessed due to the paucity of
      included trials. Conclusions/clinical implications: There is a lack of reliable
      scientific evidence to support re-mineralizing or camouflaging strategies to
      manage post-orthodontic white spot lesions. Further well-performed controlled
      clinical trials with long-term follow-up are needed to establish best clinical
      practice.

PMID- 27030285
TI  - Progranulin promotes the retinal precursor cell proliferation and the
      photoreceptor differentiation in the mouse retina.
AB  - Progranulin (PGRN) is a secreted growth factor associated with embryo
      development, tissue repair, and inflammation. In a previous study, we showed that
      adipose-derived stem cell-conditioned medium (ASC-CM) is rich in PGRN. In the
      present study, we investigated whether PGRN is associated with retinal
      regeneration in the mammalian retina. We evaluated the effect of ASC-CM using the
      N-methyl-N-nitrosourea-induced retinal damage model in mice. ASC-CM promoted the
      differentiation of photoreceptor cells following retinal damage. PGRN increased
      the number of BrdU(+) cells in the outer nuclear layer following retinal damage
      some of which were Rx (retinal precursor cell marker) positive. PGRN also
      increased the number of rhodopsin(+) photoreceptor cells in primary retinal cell
      cultures. SU11274, a hepatocyte growth factor (HGF) receptor inhibitor,
      attenuated the increase. These findings suggest that PGRN may affect the
      differentiation of retinal precursor cells to photoreceptor cells through the HGF
      receptor signaling pathway. 

PMID- 27030286
TI  - Assessing in vivo dynamics of multiple quality attributes from a therapeutic IgG4
      monoclonal antibody circulating in cynomolgus monkey.
AB  - Characterization of biopharmaceutical proteins and assessment and understanding
      of the critical quality attributes (CQAs) is a significant part of
      biopharmaceutical product development and is routinely performed in vitro. In
      contrast, systematic analysis of the quality attributes in vivo is not as
      widespread, although metabolism and clearance of multiple variants of therapeutic
      proteins administered to non-human primates and human subjects may have a
      different impact on safety, efficacy and exposure. The major hurdles of such
      studies are usually sample availability and technical capability. In this study,
      we used affinity purification coupled with liquid chromatography and mass
      spectrometric analysis of the digested protein for consistent and simultaneous
      detection of the full amino acid sequence of a therapeutic IgG4 monoclonal
      antibody, MAB1. This methodology allowed us to assess in vivo changes of all
      sequence-related modifications and quality attributes of MAB1 over the duration
      of a preclinical pharmacokinetic study in cynomolgus monkeys.

PMID- 27030288
TI  - Efficient visualization of H2S via a fluorescent probe with three electrophilic
      centres.
AB  - H2S is a reactive nucleophilic species with toxic effects towards human beings.
      Its efficient detection and marking is still a challenging job due to its similar
      nucleophilic character to a number of biothiols, like glutathione, cysteine,
      homocysteine etc. We report herein the first ever use of a chemosensor
      incorporating three electrophilic centres to achieve high sensitivity and very
      fast response time (40 s) towards H2S. 

PMID- 27030287
TI  - eNOS/iNOS and endoplasmic reticulum stress-induced apoptosis in the placentas of
      patients with preeclampsia.
AB  - Disruption of nitric oxide pathway and endoplasmic reticulum (ER) stress had been
      observed in preeclampsia (PE). However, the correlation and overall detailed
      expression profiles of ER stress-related markers and endothelial nitric oxide
      synthase/inducible nitric oxide synthase (eNOS/iNOS) in patients with PE were
      poorly understood. In this study, placental protein expression of ER stress
      related markers as well as eNOS/iNOS in normotensive control (n=32) and PE
      pregnancies (n=32) was examined by western blot. In addition, apoptosis was
      detected by terminal deoxynucleotidyl transferase-mediated nick-end labelling
      (TUNEL) staining in placentas. Compared with control, we found elevated ER stress
      response was agreeable with iNOS upregulation in placenta tissue of PE patients.
      Placental protein expression of ER stress-related markers, including GRP78,
      GRP94, p-PERK, eIF2a, p-eIF2a, XBP1, CHOP, Ire1, p-Ire1 and iNOS, was higher, and
      eNOS expression was lower in PE (P<0.05 for all); however, the expression of ATF6
      and PERK was similar in the PE and control groups. Upregulation of CHOP and iNOS
      was consistent of apoptosis increasing indicated by TUNEL staining and caspase 4
      expression upregulation in PE placenta. Our datas suggest that the exaggerated ER
      stress response and upregulated iNOS are probably associated with increased
      apoptosis in placenta of PE patients and may contribute to the pathophysiology of
      PE.

PMID- 27030289
TI  - Silver nanoparticles inhibit fish gill cell proliferation in protein-free culture
      medium.
AB  - While short-term exposures of vertebrate cells, such as from fish, can be
      performed in defined, serum-free media, long-term cultures generally require
      addition of growth factors and proteins, normally supplied with a serum
      supplement. However, proteins are known to alter nanoparticle properties by
      binding to nanoparticles. Therefore, in order to be able to study nanoparticle
      cell interactions for extended periods, the rainbow trout (Oncorhynchus mykiss)
      gill cell line, RTgill-W1, was adapted to proliferate in a commercial, serum-free
      medium, InVitrus VP-6. The newly adapted cell strain was named RTgill-W1-pf
      (protein free). These cells proliferate at a speed similar to the RTgill-W1 cells
      cultured in a fully supplemented medium containing 5% fetal bovine serum. As
      well, they were successfully cryopreserved in liquid nitrogen and fully recovered
      after thawing. Yet, senescence set in after about 10 passages in InVitrus VP-6
      medium, revealing that this medium cannot fully support long-term culture of the
      RTgill-W1 strain. The RTgill-W1-pf cell line was subsequently applied to
      investigate the effect of silver nanoparticles (AgNP) on cell proliferation over
      a period of 12 days. Indeed, cell proliferation was inhibited by 10 MUM AgNP.
      This effect correlated with high levels of silver being associated with the
      cells. The new cell line, RTgill-W1-pf, can serve as a unique representation of
      the gill cell-environment interface, offering novel opportunities to study
      nanoparticle-cell interactions without serum protein interference.

PMID- 27030290
TI  - The effects of amine/nitro/hydroxyl groups on the benzene rings of redox
      additives on the electrochemical performance of carbon-based supercapacitors.
AB  - In this work, a series of porous carbon materials with hierarchical porosities
      have been synthesized via a template carbonization method, in which cheap CaCO3
      serves as a template and glucose as a carbon precursor. During the carbonization
      process, CO2 produced by the decomposition of the CaCO3 template can act as an
      internal activating agent, significantly improving microporosity and
      mesoporosity. All the carbon materials obtained by regulating the ratio of
      glucose to CaCO3 exhibit the amorphous features with a low graphitization degree.
      Among them, the carbon-1 : 2 sample shows a high BET surface area of up to 818.5
      m(2) g(-1) and a large total pore volume of 1.78 cm(3) g(-1) as well as a
      specific capacitance of 107.0 F g(-1) at 1 A g(-1). In addition, a series of
      hydroquinone (HQ), p-aminophenol (PAP) and p-nitrophenol (PNP) as novel redox
      additives that can produce pseudo-capacitances have been added into the KOH
      electrolyte for promoting the total capacitive performances via redox reactions
      at the electrode-electrolyte interface. As expected, a 2.5-fold increase in the
      galvanostatic capacitance of 240.0 F g(-1) in the HQ-0.5 electrolyte occurs,
      compared with the conventional KOH electrolyte. Similarly, the PAP-0.5
      electrolyte and the PNP-0.5 electrolyte also show a high specific capacitance of
      184.0 F g(-1) at 2 A g(-1) (156.6 F g(-1) at 3 A g(-1)) and 153.0 F g(-1) at 3 A
      g(-1), respectively. Additionally, the three kinds of electrolytes exhibit
      excellent cyclic stability. The remarkable improvement of supercapacitors is
      attributed to the quick reversible Faradaic reactions of amine and hydroxyl
      groups adhering to the phenyl rings, which largely accelerates electron migration
      and brings additional pseudocapacitive contribution for carbon-based
      supercapacitors.

PMID- 27030291
TI  - Initial Validation of the Activity Choice Index Among Overweight Women.
AB  - PURPOSE: This prospective study was designed to evaluate psychometric properties
      of the Activity Choice Index (ACI), a measure for assessing one's choice to
      engage in more effortful, physically active behaviors in the course of daily
      routines over less-demanding, sedentary behaviors, in a sample of overweight
      women. METHOD: The sample included 192 overweight women (Mage = 37.6 +/- 7 years;
      Mbody mass index = 31.6 +/- 4.1 kg/m(2)) who were assessed at baseline and 12
      months after beginning a weight management intervention. RESULTS: The
      unidimensional factor structure was confirmed for the 6-item version of the ACI.
      Group invariance and temporal invariance were also established. Moreover, ACI
      scores were positively correlated with self-reported physical activity (as
      measured by the 7-Day Physical Activity Recall), daily pedometer steps, and 3-day
      average accelerometer counts. CONCLUSIONS: This preliminary investigation
      provides evidence that a relatively brief self-report instrument for assessing
      lifestyle physical activity choices has strong psychometric characteristics
      although convergent evidence is limited. The ACI has potential utility for
      researchers and practitioners aiming to quantify, or track change in, physical
      activity in everyday, free-living conditions. This early investigation sets the
      stage for future research to further delineate and strengthen the measurement of
      the ACI construct.

PMID- 27030292
TI  - Two mutations G335D and Q343R within the amyloidogenic core region of TDP-43
      influence its aggregation and inclusion formation.
AB  - TDP-43 is a DNA/RNA binding protein associated with TDP-43 proteinopathies. Many
      mutations have been identified in the flexible C-terminal region, which is
      implicated in the disease pathology. We investigated four point mutations in the
      amyloidogenic core region (residues 311-360) of TDP-43 by biochemical and
      spectroscopic methods. We found that the G335D mutation enhances the aggregation
      and inclusion formation of TDP-43 and this mutant in TDP-35 (the C-terminal
      fragment of 35 kDa) exaggerates the antagonist effect on RNA processing by
      endogenous TDP-43; whereas Q343R gives an opposite effect. As a comparison, M337V
      and Q331K have very little impact on the aggregation and inclusion formation of
      TDP-43 or TDP-35. NMR structural analysis showed that the G335D mutant in the
      core region forms a loop linker between the two alpha-helices and promotes alpha
      to-beta transition, but Q343R loses the second helix and consequently the
      structural transformation. Thus, the propensity of structural transformation in
      the amyloidogenic core of TDP-43 determines its aggregation and inclusion
      formation. This study may provide a molecular mechanism of the TDP-43
      proteinopathies caused by genetic mutations. 

PMID- 27030293
TI  - Liposomal doxorubicin: the good, the bad and the not-so-ugly.
AB  - There are direct and indirect indications that PEGylated liposomal doxorubicin
      (Doxil), a widely used anticancer nanomedicine, has a subclinical immune
      suppressive effect. As an example of a seemingly bad pharmacological property
      turning out to be "not-so-ugly", but actually beneficial, the authors highlight
      the potential benefits of Doxil's immune suppressive effect. These include (1)
      the decreased uptake of the drug by the MPS which may entail enhanced tumor
      uptake, and, hence, improved therapeutic efficacy; (2) the use of slow infusion
      protocols in reducing the risk of hypersensitivity (infusion) reactions; and (3),
      possible protection against hypersensitivity reactions to co-administered
      reactogenic drugs. To consider immune suppression as useful represents a paradigm
      shifts in nanotoxicology and anticancer chemotherapy.

PMID- 27030294
TI  - Molecular characterization of XopAG effector AvrGf2 from Xanthomonas fuscans ssp.
      aurantifolii in grapefruit.
AB  - Xanthomonas fuscans ssp. aurantifolii group C strains exhibit host specificity on
      different citrus species. The strains possess a type III effector, AvrGf2,
      belonging to the XopAG effector gene family, which restricts host range on
      citrus. We dissected the modular nature and mode of action of AvrGf2 in
      grapefruit resistance. XopAG effectors possess characteristic features, such as a
      chloroplast localization signal, a cyclophilin-binding domain characteristic
      amino acid sequence motif (GPLL) and a C-terminal domain-containing CLNAxYD.
      Mutation of GPLL to AASL in AvrGf2 abolished the elicitation of the
      hypersensitive response (HR), whereas mutation of only the first amino acid to
      SPLL delayed the HR in grapefruit. Yeast two-hybrid experiments showed strong
      interaction of AvrGf2 with grapefruit cyclophilin (GfCyp), whereas AvrGf2-SPLL
      and AvrGf2-AASL mutants showed weak and no interaction, respectively. Molecular
      modelling and in silico docking studies for the cyclophilin-AvrGf2 interaction
      predicted the binding of citrus cyclophilins (CsCyp, GfCyp) to hexameric peptides
      spanning the cyclophilin-binding domain of AvrGf2 and AvrGf2 mutants (VAGPLL,
      VASPLL and VAAASL) with affinities equivalent to or better than a positive
      control peptide (YSPSA) previously demonstrated to bind CsCyp. In addition, the C
      terminal domain of XopAG family effectors contains a highly conserved motif,
      CLNAxYD, which was identified to be crucial for the induction of HR based on site
      directed mutagenesis (CLNAxYD to CASAxYD). Our results suggest a model in which
      grapefruit cyclophilin promotes a conformational change in AvrGf2, thereby
      triggering the resistance response.

PMID- 27030295
TI  - Injunctive Norms and Alcohol Consumption: A Revised Conceptualization.
AB  - BACKGROUND: Injunctive norms have been found to be important predictors of
      behaviors in many disciplines with the exception of alcohol research. This
      exception is likely due to a misconceptualization of injunctive norms for alcohol
      consumption. To address this, we outline and test a new conceptualization of
      injunctive norms and personal approval for alcohol consumption. Traditionally,
      injunctive norms have been assessed using Likert scale ratings of approval
      perceptions, whereas descriptive norms and individual behaviors are typically
      measured with behavioral estimates (i.e., number of drinks consumed per week,
      frequency of drinking). This makes comparisons between these constructs difficult
      because they are not similar conceptualizations of drinking behaviors. The
      present research evaluated a new representation of injunctive norms with anchors
      comparable to descriptive norms measures. METHODS: A study and a replication were
      conducted including 2,559 and 1,189 undergraduate students from 3 different
      universities. Participants reported on their alcohol-related consumption
      behaviors, personal approval of drinking, and descriptive and injunctive norms.
      Personal approval and injunctive norms were measured using both traditional
      measures and a new drink-based measure. RESULTS: Results from both studies
      indicated that drink-based injunctive norms were uniquely and positively
      associated with drinking, whereas traditionally assessed injunctive norms were
      negatively associated with drinking. Analyses also revealed significant unique
      associations between drink-based injunctive norms and personal approval when
      controlling for descriptive norms. CONCLUSIONS: These findings provide support
      for a modified conceptualization of personal approval and injunctive norms
      related to alcohol consumption and, importantly, offer an explanation and
      practical solution for the small and inconsistent findings related to injunctive
      norms and drinking in past studies.

PMID- 27030296
TI  - Circle of Willis Collateral During Temporary Internal Carotid Artery Occlusion I:
      Observations From Digital Subtraction Angiography.
AB  - INTRODUCTION: Impaired collateral circulation can lead to stroke during carotid
      endarterectomy. Carotid stump pressure (CSP) is used as a surrogate measure of
      collateral flow. The objective was to determine whether anatomical features
      obtained from digital subtraction angiography correlate with CSP during temporary
      internal carotid artery occlusion. The second objective was to use these features
      in combination to predict CSP. METHODS: Digital subtraction angiographies from
      102 patients obtained before endarterectomy were reviewed for anatomical
      variables including: degree of ipsilateral and contralateral carotid artery
      stenosis; patency of the anterior communicating artery; presence of cross-flow
      into ipsilateral middle cerebral artery branches; and size (< or >=1 mm calibre)
      of the ipsilateral proximal anterior cerebral (A1), the contralateral A1, and the
      ipsilateral posterior communicating arteries. At surgery, systemic mean arterial
      pressure (MAP) and CSP were recorded. Multiple regression analysis was used to
      assess for anatomical features significantly associated with CSP. A "predicted
      CSP" equation was applied to 54 subsequent patients and correlated with measured
      CSP. RESULTS: Variables correlating with CSP included MAP (p=0.001); the presence
      of severe contralateral carotid stenosis (p=0.002); patency of the anterior
      communicating artery (p=0.013); and the size of the contralateral A1 segment
      (p=0.029). Angiographic cross-flow, ipsilateral A1 size, and ipsilateral
      posterior communicating artery size were not significant. Predicted CSP
      correlated significantly with measured CSP (p<0.0001; R 2=0.34). CONCLUSIONS:
      Anatomical features and systemic MAP are associated with carotid stump pressure
      during internal carotid artery occlusion and account for a significant amount of
      its variation.

PMID- 27030297
TI  - Reconstructing the complex evolutionary history of mobile plasmids in red algal
      genomes.
AB  - The integration of foreign DNA into algal and plant plastid genomes is a rare
      event, with only a few known examples of horizontal gene transfer (HGT).
      Plasmids, which are well-studied drivers of HGT in prokaryotes, have been
      reported previously in red algae (Rhodophyta). However, the distribution of these
      mobile DNA elements and their sites of integration into the plastid (ptDNA),
      mitochondrial (mtDNA), and nuclear genomes of Rhodophyta remain unknown. Here we
      reconstructed the complex evolutionary history of plasmid-derived DNAs in red
      algae. Comparative analysis of 21 rhodophyte ptDNAs, including new genome data
      for 5 species, turned up 22 plasmid-derived open reading frames (ORFs) that
      showed syntenic and copy number variation among species, but were conserved
      within different individuals in three lineages. Several plasmid-derived homologs
      were found not only in ptDNA but also in mtDNA and in the nuclear genome of green
      plants, stramenopiles, and rhizarians. Phylogenetic and plasmid-derived ORF
      analyses showed that the majority of plasmid DNAs originated within red algae,
      whereas others were derived from cyanobacteria, other bacteria, and viruses. Our
      results elucidate the evolution of plasmid DNAs in red algae and suggest that
      they spread as parasitic genetic elements. This hypothesis is consistent with
      their sporadic distribution within Rhodophyta. 

PMID- 27030298
TI  - Pyrazolones metabolites are relevant for identifying selective anaphylaxis to
      metamizole.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of
      hypersensitivity reactions, with pyrazolones the most frequent drugs inducing
      selective reactions. Immediate selective hypersensitivity to pyrazolones is
      thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests
      is low and this may be due to the incomplete characterization of the structures
      involved. Here we investigated whether main metabolites of metamizole (dipyrone)
      in human could be involved in the immune response using the basophil activation
      test (BAT). We studied subjects with confirmed selective immediate
      hypersensitivity to metamizole and performed BAT with metamizole and its
      metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4
      acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results
      showed an increase of positive results from 37.5% to 62.5% using metamizole plus
      metabolites as compared with the BAT carried out only with the parent drug,
      demonstrating that metamizole metabolites have a role in the reaction and can
      induce specific basophil activation in patients with immediate hypersensitivity
      to this drug. Our findings indicate that pyrazolone metabolites are useful for
      improving the in vitro diagnosis of allergic reactions to metamizole. 

PMID- 27030299
TI  - Cross-sectional analysis between prostate volumes and serum sex hormones in
      Japanese men attending a urological clinic.
AB  - AIM: To evaluate epidemiologically the association between measured prostate
      volume and sex hormones. METHODS: Between December 2012 and September 2014, 226
      patients attending the urological clinic were assessed for the relationship
      between prostate volume (PV) and, serum sex hormones, physical size, personal
      habits, etc. Prostate volume was measured by using transabdominal
      ultrasonography. Statistically, the Pearson correlation coefficients test was
      used. RESULTS: Total cases, the cases of PV <= 25 ml, and the cases of PV > 25 ml
      were evaluated respectively. Total cases and the cases of PV > 25 ml showed a
      positive significant correlation with testosterone (T), but the cases of PV <= 25
      ml showed no such correlation. The cases of PV > 25 ml had a positive significant
      correlation with estradiol (E2), but total cases and cases of PV <= 25 ml did
      not. Dehydroepiandrosterone sulfate (DHEAS) showed no correlation with any case
      of PV, however it decreased significantly with age and had a correlation with
      alopecia. The E2/T ratio had no correlation with any case of PV, but on the other
      hand, the T/DHEAS and E2/DHEAS ratios had significant positive correlation with
      PV > 25 ml. CONCLUSIONS: Serum T and E2 had significant positive correlation with
      measured PV especially in larger prostates. This result seems to correspond with
      the conventional theory that T and E2 have an etiological effect on benign
      prostatic hyperplasia. DHEAS did not show direct correlation with PV, however it
      appeared to suppress the role of T and E2 on benign prostatic hyperplasia growth.
      DHEAS might be a key to understanding the etiology of benign prostatic
      hyperplasia with aging.

PMID- 27030300
TI  - Laparoscopic versus open gastrectomy for gastric cancer.
AB  - BACKGROUND: Gastric cancer is the third most common cause of cancer-related
      mortality in the world. Currently there are two surgical options for potentially
      curable patients (i.e. people with non-metastatic gastric cancer), laparoscopic
      and open gastrectomy. However, it is not clear whether one of these options is
      superior. OBJECTIVES: To assess the benefits and harms of laparoscopic
      gastrectomy or laparoscopy-assisted gastrectomy versus open gastrectomy for
      people with gastric cancer. In particular, we planned to investigate the effects
      by patient groups, such as cancer stage, anaesthetic risk, and body mass index
      (BMI), and by intervention methods, such as method of anastomosis, type of
      gastrectomy and laparoscopic or laparoscopically-assisted gastrectomy. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov and the
      WHO ICTRP (World Health Organization International Clinical Trials Registry
      Platform) until September 2015. We also screened reference lists from included
      trials. SELECTION CRITERIA: Two review authors independently selected references
      for further assessment by going through all titles and abstracts. Further
      selection was based on review of full text articles for selected references. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted study data.
      We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary
      outcomes, the mean difference (MD) or the standardised mean difference (SMD) with
      95% CI for continuous outcomes and the hazard ratio (HR) for time-to-event
      outcomes. We performed meta-analyses where it was meaningful. MAIN RESULTS: In
      total, 2794 participants were randomised in 13 trials included in this review.
      All the trials were at unclear or high risk of bias. One trial (which included 53
      participants) did not contribute any data to this review. A total of 213
      participants were excluded in the remaining trials after randomisation, leaving a
      total of 2528 randomised participants for analysis, with 1288 undergoing
      laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the
      participants were suitable for major surgery.There was no difference in the
      proportion of participants who died within thirty days of treatment between
      laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta
      analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10;
      risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11;
      I(2) = 0%; low quality evidence). There were no events in either group for short
      term recurrence (participants = 103; studies = 3), proportion requiring blood
      transfusion (participants = 66; studies = 2), and proportion with positive
      margins at histopathology (participants = 28; studies = 1). None of the trials
      reported health-related quality of life, time to return to normal activity or
      time to return to work. The differences in long-term mortality (HR 0.94, 95% CI
      0.70 to 1.25; participants = 195; studies = 3; I(2) = 0%; very low quality
      evidence), serious adverse events within three months (laparoscopic gastrectomy
      (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR
      0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I(2) = 0%; very low
      quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30;
      participants = 162; studies = 4; very low quality evidence), adverse events
      within three months (laparoscopic gastrectomy (204/268: adjusted proportion =
      16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01;
      participants = 2490; studies = 11; I(2) = 38%; very low quality evidence),
      quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38;
      participants = 143; studies = 2; I(2) = 0%; very low quality evidence), length of
      hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies =
      6; I(2) = 83%; very low quality evidence), and number of lymph nodes harvested
      (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I(2) = 40%;
      very low quality evidence) were imprecise. There was no alteration in the
      interpretation of the results in any of the subgroups. AUTHORS' CONCLUSIONS:
      Based on low quality evidence, there is no difference in short-term mortality
      between laparoscopic and open gastrectomy. Based on very low quality evidence,
      there is no evidence for any differences in short-term or long-term outcomes
      between laparoscopic and open gastrectomy. However, the data are sparse, and the
      confidence intervals were wide, suggesting that significant benefits or harms of
      laparoscopic gastrectomy cannot be ruled out. Several trials are currently being
      conducted and interim results of these trials have been included in this review.
      These trials need to perform intention-to-treat analysis to ensure that the
      results are reliable and report the results according to the CONSORT Statement.

PMID- 27030301
TI  - Laparoscopic versus open transhiatal oesophagectomy for oesophageal cancer.
AB  - BACKGROUND: Surgery is the preferred treatment for resectable oesophageal
      cancers, and can be performed in different ways. Transhiatal oesophagectomy
      (oesophagectomy without thoracotomy, with a cervical anastomosis) is one way to
      resect oesophageal cancers. It can be performed laparoscopically or by open
      method. With other organs, laparoscopic surgery has been shown to reduce
      complications and length of hospital stay compared to open surgery. However,
      concerns remain about the safety of laparoscopic transhiatal oesophagectomy in
      terms of post-operative complications and oncological clearance compared with
      open transhiatal oesophagectomy. OBJECTIVES: To assess the benefits and harms of
      laparoscopic versus open oesophagectomy for people with oesophageal cancer
      undergoing transhiatal oesophagectomy. SEARCH METHODS: We electronically searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane
      Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers
      until August 2015. We also searched the references of included trials to identify
      further trials. SELECTION CRITERIA: We considered randomised controlled trials
      and non-randomised studies comparing laparoscopic with open transhiatal
      oesophagectomy in patients with resectable oesophageal cancer, regardless of
      language, blinding, or publication status for the review. DATA COLLECTION AND
      ANALYSIS: Three review authors independently identified trials, assessed risk of
      bias and extracted data. We calculated the risk ratio (RR) or hazard ratio (HR)
      with 95% confidence intervals (CI), using both fixed-effect and random-effects
      models, with RevMan 5, based on intention-to-treat analyses. MAIN RESULTS: We
      found no randomised controlled trials on this topic. We included six non
      randomised studies (five retrospective) that compared laparoscopic versus open
      transhiatal oesophagectomy (334 patients: laparoscopic = 154 patients; open = 180
      patients); five studies (326 patients: laparoscopic = 151 patients; open = 175
      patients) provided information for one or more outcomes. Most studies included a
      mixture of adenocarcinoma and squamous cell carcinoma and different stages of
      oesophageal cancer, without metastases. All the studies were at unclear or high
      risk of bias; the overall quality of evidence was very low for all the
      outcomes.The differences between laparoscopic and open transhiatal oesophagectomy
      were imprecise for short-term mortality (laparoscopic = 0/151 (adjusted
      proportion based on meta-analysis estimate: 0.5%) versus open = 2/175 (1.1%); RR
      0.44; 95% CI 0.05 to 4.09; participants = 326; studies = 5; I2 = 0%); long-term
      mortality (HR 0.97; 95% CI 0.81 to 1.16; participants = 193; studies = 2; I2 =
      0%); anastomotic stenosis (laparoscopic = 4/36 (11.1%) versus open = 3/37 (8.1%);
      RR 1.37; 95% CI 0.33 to 5.70; participants = 73; studies = 1); short-term
      recurrence (laparoscopic = 1/16 (6.3%) versus open = 0/4 (0%); RR 0.88; 95% CI
      0.04 to 18.47; participants = 20; studies = 1); long-term recurrence (HR 1.00;
      95% CI 0.84 to 1.18; participants = 173; studies = 2); proportion of people who
      required blood transfusion (laparoscopic = 0/36 (0%) versus open = 6/37 (16.2%);
      RR 0.08; 95% CI 0.00 to 1.35; participants = 73; studies = 1); proportion of
      people with positive resection margins (laparoscopic = 15/102 (15.8%) versus open
      = 27/111 (24.3%); RR 0.65; 95% CI 0.37 to 1.12; participants = 213; studies = 3;
      I2 = 0%); and the number of lymph nodes harvested during surgery (median
      difference between the groups varied from 12 less to 3 more lymph nodes in the
      laparoscopic compared to the open group; participants = 326; studies = 5).The
      proportion of patients with serious adverse events was lower in the laparoscopic
      group (10/99, (10.3%) compared to the open group = 24/114 (21.1%); RR 0.49; 95%
      CI 0.24 to 0.99; participants = 213; studies = 3; I2 = 0%); as it was for adverse
      events in the laparoscopic group = 37/99 (39.9%) versus the open group = 71/114
      (62.3%); RR 0.64; 95% CI 0.48 to 0.86; participants = 213; studies = 3; I2 = 0%);
      and the median lengths of hospital stay were significantly less in the
      laparoscopic group than the open group (three days less in all three studies that
      reported this outcome; number of participants = 266). There was lack of clarity
      as to whether the median difference in the quantity of blood transfused was
      statistically significant favouring laparoscopic oesophagectomy in the only study
      that reported this information. None of the studies reported post-operative
      dysphagia, health-related quality of life, time-to-return to normal activity
      (return to pre-operative mobility without caregiver support), or time-to-return
      to work. AUTHORS' CONCLUSIONS: There are currently no randomised controlled
      trials comparing laparoscopic with open transhiatal oesophagectomy for patients
      with oesophageal cancers. In observational studies, laparoscopic transhiatal
      oesophagectomy is associated with fewer overall complications and shorter
      hospital stays than open transhiatal oesophagectomy. However, this association is
      unlikely to be causal. There is currently no information to determine a causal
      association in the differences between the two surgical approaches. Randomised
      controlled trials comparing laparoscopic transhiatal oesophagectomy with other
      methods of oesophagectomy are required to determine the optimal method of
      oesophagectomy.

PMID- 27030302
TI  - The Terminal Oxidase Cytochrome bd Promotes Sulfide-resistant Bacterial
      Respiration and Growth.
AB  - Hydrogen sulfide (H2S) impairs mitochondrial respiration by potently inhibiting
      the heme-copper cytochrome c oxidase. Since many prokaryotes, including
      Escherichia (E.) coli, generate H2S and encounter high H2S levels particularly in
      the human gut, herein we tested whether bacteria can sustain sulfide-resistant O2
      dependent respiration. E. coli has three respiratory oxidases, the cyanide
      sensitive heme-copper bo3 enzyme and two bd oxidases much less sensitive to
      cyanide. Working on the isolated enzymes, we found that, whereas the bo3 oxidase
      is inhibited by sulfide with half-maximal inhibitory concentration IC50 = 1.1 +/-
      0.1 MUM, under identical experimental conditions both bd oxidases are insensitive
      to sulfide up to 58 MUM. In E. coli respiratory mutants, both O2-consumption and
      aerobic growth proved to be severely impaired by sulfide when respiration was
      sustained by the bo3 oxidase alone, but unaffected by <=200 MUM sulfide when
      either bd enzyme acted as the only terminal oxidase. Accordingly, wild-type E.
      coli showed sulfide-insensitive respiration and growth under conditions favouring
      the expression of bd oxidases. In all tested conditions, cyanide mimicked the
      functional effect of sulfide on bacterial respiration. We conclude that bd
      oxidases promote sulfide-resistant O2-consumption and growth in E. coli and
      possibly other bacteria. The impact of this discovery is discussed. 

PMID- 27030303
TI  - INDIVIDUALIZED YOGA FOR REDUCING DEPRESSION AND ANXIETY, AND IMPROVING WELL
      BEING: A RANDOMIZED CONTROLLED TRIAL.
AB  - BACKGROUND: Depression and anxiety are leading causes of disability worldwide.
      Current treatments are primarily pharmaceutical and psychological. Questions
      remain about effectiveness and suitability for different people. Previous
      research suggests potential benefits of yoga for reducing depression and anxiety.
      The aim of this study is to investigate the effects of an individualized yoga
      intervention. METHODS: A sample of 101 people with symptoms of depression and/or
      anxiety participated in a randomized controlled trial comparing a 6-week yoga
      intervention with waitlist control. Yoga was additional to usual treatment. The
      control group was offered the yoga following the waitlist period. Measures
      included Depression Anxiety Stress Scale (DASS-21), Kessler Psychological
      Distress Scale (K10), Short-Form Health Survey (SF12), Scale of Positive and
      Negative Experience (SPANE), Flourishing Scale (FS), and Connor-Davidson
      Resilience Scale (CD-RISC2). RESULTS: There were statistically significant
      differences between yoga and control groups on reduction of depression scores (
      4.30; 95% CI: -7.70, -0.01; P = .01; ES -.44). Differences in reduced anxiety
      scores were not statistically significant (-1.91; 95% CI: -4.58, 0.76; P = .16).
      Statistically significant differences in favor of yoga were also found on total
      DASS (P = .03), K10, SF12 mental health, SPANE, FS, and resilience scores (P <
      .01 for each). Differences in stress and SF12 physical health scores were not
      statistically significant. Benefits were maintained at 6-week follow-up.
      CONCLUSION: Yoga plus regular care was effective in reducing symptoms of
      depression compared with regular care alone. Further investigation is warranted
      regarding potential benefits in anxiety. Individualized yoga may be particularly
      beneficial in mental health care in the broader community.

PMID- 27030304
TI  - Two progressive pathways of microinvasive carcinoma: low-grade luminal pathway
      and high-grade HER2 pathway based on high tumour-infiltrating lymphocytes.
AB  - AIMS: While cancer immunity is involved in tumour progression from the very early
      stage, no detailed study has been reported on the relationship between 'early
      stage' breast cancer and tumour-infiltrating lymphocytes (TILs). We focused on
      microinvasive carcinoma to investigate the relationship between histological
      tumour factors and immunity in 'early' breast cancer. METHODS: Of 2593 resected
      breast carcinomas, 46 microinvasive carcinomas (1.8%) were included. The
      relationships between tumour characteristics (invasive form, grade, comedo,
      subtype) and immunological characteristics (TIL, healing) were examined. The
      invasive form was divided into 'cluster-like' (ie, invasive foci consisted of a
      small number of cancer cells) and 'non-cluster-like' (ie, nested and classifiable
      into particular histological type). RESULTS: Among all cases, 34.8% were grade 1.
      ER+HER2-, ER+HER2+, ER-HER2+ and ER-HER2- accounted for 58.7%, 8.7%, 28.3% and
      4.3%, respectively. Compared with ER+HER2-, ER-HER2+ cases had a significantly
      stronger association with grade 3 (92.3% vs 0%), comedo (100% vs 55.6%), high TIL
      (100% vs 29.3%), high CD8+ TIL (92.3% vs 33.3%) and healing (76.9% vs 14.8%)
      (p<0.001). Compared with 'non-cluster-like', 'cluster-like' carcinoma showed
      significantly higher rates of HER2 positivity (69.2% vs 24.2%), high TIL (92.3%
      vs 42.4%) and high CD8+ TIL (76.9% vs 39.4%) (p<0.01). CONCLUSIONS: Our study
      revealed that microinvasive carcinoma has two progressive pathways; 'low-grade
      luminal pathway' and 'high-grade HER2 pathway'. HER2-positive cases showed the
      following unique characteristics: 'high-grade; comedo, high TIL and CD8+ TIL;
      healing; cluster-like invasion'. These results suggest that the cluster-like
      invasion might occur because of tumour immunity that leads to disruption of the
      duct and formation of microinvasive carcinoma in HER2-positive cases.

PMID- 27030305
TI  - Expression of embryonic stem cell markers in keloid-associated lymphoid tissue.
AB  - AIMS: To identify, characterise and localise the population of primitive cells in
      keloid scars (KS). METHODS: 5-um-thick formalin-fixed paraffin-embedded sections
      of KS samples from 10 patients underwent immunohistochemical (IHC) staining for
      the embryonic stem cell (ESC) markers OCT4, SOX2, pSTAT3 and NANOG, and keloid
      associated lymphoid tissue (KALT) markers CD4 and CD20. NanoString gene
      expression analysis and in situ hybridisation (ISH) were used to determine the
      abundance and localisation of the mRNA for these ESC markers. RESULTS: IHC
      staining revealed the expression of the ESC markers OCT4, SOX2, pSTAT3 and NANOG
      by a population of cells within KS tissue. These are localised to the endothelium
      of the microvessels within the KALTs. NanoString gene expression analysis
      confirmed the abundance of the transcriptional expression of the same ESC
      markers. ISH localised the expression of the ESC transcripts to the primitive
      endothelium in KS tissue. CONCLUSIONS: This report demonstrates the expression of
      ESC markers OCT4, SOX2, pSTAT3 and NANOG by the endothelium of the microvessels
      within the KALTs. These findings show a unique niche of primitive cells within
      KS, expressing ESC markers, revealing a potential therapeutic target in the
      treatment of KS.

PMID- 27030306
TI  - The day we started HPV triage.
AB  - AIMS: Following the introduction of the triage test in cervical screening, which
      was designed to identify a subgroup who were at risk of underlying high-grade
      cervical intraepithelial neoplasia (CIN), there has been a significant change in
      the number and profile of cervical biopsies. In this study, analysis of the
      progressive change in diagnostic categories has been performed to identify the
      impact of the triage test on the service. METHODS: Cases referred for colposcopy,
      with corresponding subsequent tissue diagnoses, were identified by electronic
      search of the histopathology accession database using suitable coding terms for
      the period between October and April of four consecutive years. A likelihood
      ratio test was devised to assess the significance of the observed progressive
      increase in total numbers of cervical biopsies. RESULTS: As anticipated from the
      pilot studies, implementation of the new guidelines led to a significant increase
      in the number of women referred for colposcopy. However, the annual increase was
      greater than expected. During this period, there was a change in the profile of
      histological diagnoses, characterised by: conspicuous rise in the number of
      cervical biopsies reported as 'human papillomavirus change only' or 'CIN1' (21
      29% and 12-21%, of the total cervical biopsies, respectively); fall in mean CIN
      scores. CONCLUSIONS: The change in guidelines has led to an increase in patients
      referred for colposcopy; in turn this has led to an increase in number of
      specimens (particularly those with lower grades of dysplasia) submitted for
      histological assessment. This change of workload profile has implications for
      resourcing services for colposcopy and histopathology.

PMID- 27030307
TI  - Improved quality of patient care through routine second review of histopathology
      specimens prior to multidisciplinary meetings.
AB  - AIM: Double reading may be a valuable tool for improving quality of patient care
      by identifying diagnostic errors before final sign-out, but standard double
      reading would significantly increase costs of pathology. We assessed the added
      value of intradepartmental routine double reading of histopathology specimens
      prior to multidisciplinary meetings. METHODS: Diagnoses, treatment plans and
      prognoses of patients are often discussed at multidisciplinary meetings. As part
      of the daily routine, all pathology specimens to be discussed at upcoming
      multidisciplinary meetings undergo prior intradepartmental double reading. We
      identified all histopathology specimens from 2013 that underwent such double
      reading and determined major and minor discordance rates based on clinical
      relevance between the initial and consensus sign-out diagnoses. RESULTS: We
      included 6796 histopathology specimens that underwent double reading,
      representing approximately 8% of all histopathology cases at our institution in
      2013. Double reading diagnoses were concordant in 6566 specimens (96.6%). Major
      and minor discordances were observed in 60 (0.9%) and 170 (2.5%) specimens,
      respectively. Urology specimens had significantly more discordances than other
      tissues of origin, Gleason grading of prostate cancer biopsies being the most
      frequent diagnostic problem. Furthermore, premalignant and malignant cases showed
      significantly higher discordance rates than the rest. The vast majority (90%) of
      discordances represented changes within the same diagnostic category (eg,
      malignant to malignant). CONCLUSIONS: Routine double reading of histopathology
      specimens prior to multidisciplinary meetings prevents diagnostic errors. It
      resulted in about 1% discordant diagnoses of potential clinical significance,
      indicating that second review is worthwhile in terms of patient safety and
      quality of patient care.

PMID- 27030308
TI  - Can we use subchondral bone thickness on high-field magnetic resonance images to
      identify Thoroughbred racehorses at risk of catastrophic lateral condylar
      fracture?
AB  - REASONS FOR PERFORMING STUDY: Fractures of the lateral condyle of the third
      metacarpus (MC3) are a significant welfare concern in horseracing worldwide.
      OBJECTIVES: The primary aim of this work was to identify magnetic resonance (MR)
      image-detectable prefracture markers that have the potential for use as a
      screening tool to identify horses at significant risk of catastrophic fracture.
      STUDY DESIGN: Case-control study of bone-level risk factors for fracture in
      racehorses. METHODS: A total of 191 MC3s from horses, with and without lateral
      condylar fracture of MC3, were subjected to MR imaging. The depth of dense
      subchondral/trabecular bone was measured at several sites around the distal end
      of the bone and regression analyses were conducted to identify differences in
      this depth between horses with and without lateral condylar fracture. RESULTS:
      Greater depth of dense subchondral/trabecular bone in the palmar half of the
      lateral parasagittal groove of distal MC3 was associated with an increased
      likelihood of being from a horse that had sustained a fracture. Receiver operator
      characteristic analysis was used to identify the optimal cut-off in the depth of
      dense subchondral/trabecular bone at this site to best discriminate fracture
      status. Positive and negative predictive values were calculated using the
      prevalence of fracture within the current study and also a prevalence estimate
      for the wider racehorse population. CONCLUSIONS: There is a requirement to
      identify suitable prescreening test(s) to eliminate many true negative horses and
      increase the prevalence of prefracture pathology in the sub population that would
      be screened using MR imaging, in turn maximising the positive predictive value of
      this test.

PMID- 27030309
TI  - Fabrication of Large-Area Two-Dimensional Microgel Colloidal Crystals via
      Interfacial Thiol-Ene Click Reaction.
AB  - A method for the fabrication of high quality, large area 2D colloidal crystals
      (CCs) using poly(N-isopropylacrylamide) (PNIPAM) microgel sphere, an extremely
      soft colloid, as building block was proposed. First the microgel spheres were
      assembled into 3D colloidal crystals. The first 111 plane of the 3D crystal close
      to the substrate was then fixed in situ onto the substrate. Highly efficient
      photoinitiated thiol-ene coupling was chosen for the fixing purpose. Thanks to
      the high quality of 3D microgel CCs, the resulting 2D CCs exhibit a high degree
      of ordering. Large area 2D CCs were fabricated because large area 3D microgel CCs
      can be facilely fabricated. Besides planar substrates, the method allows the
      fabrication of 2D CCs on curved surface, too. In addition, the interpartical
      distance in the 2D CCs can be tuned by the concentration of the microgel
      dispersion.

PMID- 27030310
TI  - Mindfulness reduces the correspondence bias.
AB  - The correspondence bias (CB) refers to the idea that people sometimes give undue
      weight to dispositional rather than situational factors when explaining
      behaviours and attitudes. Three experiments examined whether mindfulness, a non
      judgmental focus on the present moment, could reduce the CB. Participants engaged
      in a brief mindfulness exercise (the raisin task), a control task, or an
      attention to detail task before completing a typical CB measure involving an
      attitude-attribution paradigm. The results indicated that participants in the
      mindfulness condition experienced a significant reduction in the CB compared to
      participants in the control or attention to detail conditions. These results
      suggest that mindfulness training can play a unique role in reducing social
      biases related to person perception.

PMID- 27030311
TI  - Structure and dynamics of proflavine association around DNA.
AB  - Proflavine is a small molecule that intercalates into DNA and, thereby, acts as
      an anticancer agent. Intercalation of proflavine is shown to be a two-step
      process in which the first step is believed to be the formation of a pre
      intercalative outside bound state. Experimental studies so far have been unable
      to capture the nature of the outside bound state. However, the sub-millisecond
      timescale observed in fluorescence kinetic experiments is often attributed to the
      binding of proflavine outside of DNA. Here, we have performed molecular dynamics
      simulations with multiple proflavine molecules to study the structure and
      dynamics of the formation of the outside bound state of DNA at different ion
      concentrations. We observed that the timescale of the outside bound state
      formation is, at least, five orders of magnitude faster (in nanoseconds) than the
      experimentally reported timescale (sub-milliseconds) attributed to binding
      outside DNA. Moreover, we also observed the stacked arrangement of proflavine all
      around DNA, which is different from the experimentally predicted stacking
      arrangement perpendicular to the helical axis of DNA in the close vicinity of the
      phosphate groups. This study, therefore, provides insight into the molecular
      structure and dynamics of the pre-intercalative outside bound state and will help
      in understanding the overall intercalation mechanism. 

PMID- 27030313
TI  - Use of antimicrobials for animals in New Zealand, and in comparison with other
      countries.
AB  - AIM: To describe the use of antimicrobial drugs for food animals in New Zealand,
      based on sales data reported to government, changes over time, and in comparison
      with other countries and human use. METHODS: Data were sourced from official
      government and industry reports covering 26 European countries, Australia,
      Canada, New Zealand and the United States of America in 2012, the last year data
      were available for all countries. The data included antimicrobial sales, and
      animal and human populations. Antimicrobial use was estimated based on the amount
      of active ingredient sold, per standardised biomass (population correction unit).
      RESULTS: The estimated usage of antimicrobials for food animals in New Zealand
      for 2012 was 9.4 mg active ingredient/kg biomass. Total sales of antimicrobials
      between 2005-14 increased on average by 2.5% or 1.5 tonnes per year. Over the
      same time total animal biomass decreased by an estimated 4.3%, with the main
      decrease being in sheep (25%) and beef cattle (17%), while dairy cattle increased
      (28%). In the countries examined, the estimated usage of antimicrobials in food
      producing animals in 2012 varied from 3.8 to 341 mg active ingredient/kg biomass,
      in Norway and Italy, respectively, with use in New Zealand being the third
      lowest. Usage of antimicrobials for human health in New Zealand in 2012 was
      estimated at 121 mg active ingredient/kg biomass, being ranked sixteenth of the
      countries compared. Use in humans was 12.9 times the use in animals. CONCLUSIONS:
      New Zealand was the third lowest user of antimicrobials in animal production and
      used much less than in human medicine. This is the first report of baseline data
      which may be used by the New Zealand animal health industry to develop, and
      measure success in, approaches to maximise the life of antimicrobials for animal
      health and welfare. CLINICAL RELEVANCE: New Zealand veterinarians will soon have
      to make changes to adopt the World Health Organisation's global action plan to
      manage antimicrobial resistance. Having a benchmark of current antimicrobial use
      will inform priorities and allow measurement of the impact of future programmes.

PMID- 27030312
TI  - Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study.
AB  - AIMS/HYPOTHESIS: Type 1 diabetes mellitus is a major public health problem of
      increasing global concern, with potential neurological complications. A possible
      association exists between type 1 diabetes and subsequent epilepsy. This study
      evaluated the relationship between type 1 diabetes and epilepsy in Taiwan.
      METHODS: Claims data from the Taiwan National Health Insurance Research Database
      were used to conduct retrospective cohort analyses. The study cohort contained
      2568 patients with type 1 diabetes, each of whom was frequency-matched by sex,
      urbanisation of residence area and index year with ten patients without type 1
      diabetes. Cox proportional hazard regression analysis was conducted to estimate
      the effects of type 1 diabetes on epilepsy risk. RESULTS: In patients with type 1
      diabetes, the risk of developing epilepsy was significantly higher than that in
      patients without type 1 diabetes (p < 0.0001 for logrank test). After adjustment
      for potential confounders, the type 1 diabetes cohort was 2.84 times as likely to
      develop epilepsy than the control cohort was (HR 2.84 [95% CI 2.11, 3.83]).
      CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes are at an increased
      risk of developing epilepsy. Metabolic abnormalities of type 1 diabetes, such as
      hyperglycaemia and hypoglycaemia, may have a damaging effect on the central
      nervous system and be associated with significant long-term neurological
      sequelae. The causative factors between type 1 diabetes and the increased risk of
      epilepsy require further investigation.

PMID- 27030314
TI  - Total hip arthroplasty and total knee arthroplasty in a patient with congenital
      deficiency of plasminogen activator inhibitor-1.

PMID- 27030316
TI  - Comprehensive metabolite profiling of Plantaginis Semen using ultra high
      performance liquid chromatography with electrospray ionization quadrupole time-of
      flight tandem mass spectrometry coupled with elevated energy technique.
AB  - Plantaginis Semen is commonly used in traditional medicine to treat edema,
      hypertension, and diabetes. The commercially available Plantaginis Semen in China
      mainly comes from three species. To clarify the chemical composition and distinct
      different species of Plantaginis Semen, we established a metabolite profiling
      method based on ultra high performance liquid chromatography with electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry coupled with
      elevated energy technique. A total of 108 compounds, including phenylethanoid
      glycosides, flavonoids, guanidine derivatives, terpenoids, organic acids, and
      fatty acids, were identified from Plantago asiatica L., P. depressa Willd., and
      P. major L. Results showed significant differences in chemical components among
      the three species, particularly flavonoids. This study is the first to provide a
      comprehensive chemical profile of Plantaginis Semen, which could be involved into
      the quality control, medication guide, and developing new drug of Plantago seeds.

PMID- 27030315
TI  - Post-transplant bendamustine reduces GvHD while preserving GvL in experimental
      haploidentical bone marrow transplantation.
AB  - Advances in haploidentical bone marrow transplantation (h-BMT) have drastically
      broadened the treatment options for patients requiring BMT. The possibility of
      significantly reducing the complications resulting from graft-versus-host disease
      (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has
      substantially improved the efficacy and applicability of T cell-replete h-BMT.
      However, higher frequency of disease recurrence remains a major challenge in h
      BMT with PT-CY. There is a critical need to identify novel strategies to prevent
      GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT. To this end,
      we evaluated the impact of bendamustine (BEN), given post-transplant, on GvHD and
      GvL using clinically relevant murine h-BMT models. We provide results indicating
      that post-transplant bendamustine (PT-BEN) alleviates GvHD, significantly
      improving survival, while preserving engraftment and GvL effects. We further
      document that PT-BEN can mitigate GvHD even in the absence of Treg. Our results
      also indicate that PT-BEN is less myelosuppressive than PT-CY, significantly
      increasing the number and proportion of CD11b(+) Gr-1(hi) cells, while decreasing
      lymphoid cells. In vitro we observed that BEN enhances the suppressive function
      of myeloid-derived suppressor cells (MDSCs) while impairing the proliferation of
      T- and B-cells. These results advocate for the consideration of PT-BEN as a new
      therapeutic platform for clinical implementation in h-BMT.

PMID- 27030317
TI  - "Juggling" Behavior in Wild Hainan Gibbons, a New Finding in Nonhuman Primates.
AB  - Many species of primates use tools and manipulate objects. Environmental objects,
      such as sticks and branches, are used in locomotion, display, conflict, nesting,
      and foraging. This study presents observations regarding endangered male Hainan
      gibbons (Nomascus hainanus) selecting sticks and then throwing and catching them
      repeatedly. This act of Hainan gibbons was termed as "juggling" behavior. This
      study is the first record of branch use of this kind in free-living gibbons.
      While it is impossible to experiment on this only remaining population of Hainan
      gibbons, the deliberate acquisition and then throwing and catching of a stick
      raises myriad questions regarding their function. The study determined that the
      juggling behavior of Hainan gibbons, in the process of their brachiation, helps
      them accurately judge the distance and support strength of an object. It was also
      found that an adult individual's proficiency in juggling behavior was much higher
      than that of a youth. Of all gibbon species, the juggling behavior of Hainan
      gibbon has a high degree of behavior refinement. Gibbons have the longest forearm
      than any other primates, which helps them in such performances-a unique mechanism
      that allows them to perform such unique activities, including juggling. 

PMID- 27030318
TI  - MicroRNA-29b promotes the adipogenic differentiation of human adipose tissue
      derived stromal cells.
AB  - OBJECTIVE: Obesity is primarily characterized by the accumulation of large
      amounts of fat in adipose tissue. Within the adipose tissue, adipocytes are
      derived from adipose tissue-derived stromal cells (ADSCs) via a specialized cell
      lineage differentiation process, and ADSCs play a key role in the generation and
      metabolism of adipose tissue. This study investigated whether microRNAs (miRNAs)
      play a role in adipocyte differentiation. METHODS: Using luciferase reporter and
      ChIP assays, the relationship between miR-29b, SP1, and TNF-alpha was examined.
      RESULTS: During the normal adipogenic differentiation of ADSCs, up-regulation of
      miR-29b promoted adipogenesis by enhancing SP1-mediated inhibition of TNF-alpha.
      CONCLUSIONS: This study investigated the regulatory role of miR-29b during the
      adipogenic differentiation of ADSCs and found that miR-29b is an effective
      positive regulator of adipogenesis.

PMID- 27030319
TI  - Genome-wide significant results identified for plasma apolipoprotein H levels in
      middle-aged and older adults.
AB  - Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been
      associated with negative health outcomes. ApoH levels have high heritability. We
      undertook a genome-wide association study of ApoH levels using the largest sample
      to date and replicated the results in an independent cohort (total N = 1,255). In
      the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing
      Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed
      genome-wide significant results in or near the APOH gene on chromosome 17 (top
      SNP, rs7211380, p = 1 * 10(-11)). The results were replicated in an independent
      cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint
      analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH
      levels. The set of independent SNPs identified by COJO explained 23% of the
      variance. The relationships between the top SNPs and
      cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS,
      with suggestive results observed for diabetes and cognitive performance. However,
      replication of these results in the smaller OATS cohort was not found. This work
      provides impetus for future research to better understand the contribution of
      genetics to ApoH levels and its possible impacts on health. 

PMID- 27030320
TI  - 1,7-Naphthodiyne: a new platform for the synthesis of novel, sterically congested
      PAHs.
AB  - The synthesis of an efficient precursor of the novel 1,7-naphthodiyne synthon is
      reported. Preliminary experiments demonstrate the usefulness of this platform for
      the synthesis of sterically congested polyarenes, such as helicenes and angularly
      fused acene derivatives. Furthermore, a novel intramolecular aryne trapping
      reaction is described. 

PMID- 27030322
TI  - From microgalaxies to micro-oceans to Warhol's cellular images: the art in
      science of MicroTAS 2015.

PMID- 27030321
TI  - Hilar somatostatin interneuron loss reduces dentate gyrus inhibition in a mouse
      model of temporal lobe epilepsy.
AB  - OBJECTIVE: In patients with temporal lobe epilepsy, seizures usually start in the
      hippocampus, and dentate granule cells are hyperexcitable. Somatostatin
      interneurons are a major subpopulation of inhibitory neurons in the dentate
      gyrus, and many are lost in patients and animal models. However, surviving
      somatostatin interneurons sprout axon collaterals and form new synapses, so the
      net effect on granule cell inhibition remains unclear. METHODS: The present study
      uses optogenetics to activate hilar somatostatin interneurons and measure the
      inhibitory effect on dentate gyrus perforant path-evoked local field potential
      responses in a mouse model of temporal lobe epilepsy. RESULTS: In controls, light
      activation of hilar somatostatin interneurons inhibited evoked responses up to
      40%. Epileptic pilocarpine-treated mice exhibited loss of hilar somatostatin
      interneurons and less light-induced inhibition of evoked responses. SIGNIFICANCE:
      These findings suggest that severe epilepsy-related loss of hilar somatostatin
      interneurons can overwhelm the surviving interneurons' capacity to compensate by
      sprouting axon collaterals.

PMID- 27030323
TI  - [Pneumonia at a multidisciplinary hospital].
AB  - AIM: To reveal the clinical and morphological features and predictors of a fatal
      outcome in patients with community-acquired pneumonia. MATERIAL AND METHODS: The
      results of almost 6,500 autopsies were studied; out of them there were 1631 (25%)
      deaths from pneumonia: 134 and 1497 cases occurring at home and at hospital,
      respectively. RESULTS: Both groups were considered in terms of pneumonia as a
      primary disease or as a fatal complication, with 6.4% having the former and 93.6%
      having a fatal complication of chronic obstructive pulmonary disease, chronic
      alcohol intoxication, cardiovascular diseases, or cancers. After negative
      prognosis assessment using the CURB-65 scale, pneumonia was rated as severe and
      requiring admission to the intensive care unit in 92% of the cases; PORT scale
      assessment showed that 60% cases of pneumonia necessitated hospitalizations to
      these units. The major clinical and morphological form of pneumonia was
      established to be disseminated, lobular, or overwhelming. CONCLUSION: In
      practice, risk factors for death are underestimated; the disease course is not
      monitored; current diagnostic and therapeutic approaches are inadequately
      applied.

PMID- 27030324
TI  - [Morphometric characteristics of the bronchial tree in smokers with and without
      chronic obstructive pulmonary disease].
AB  - AIM: To reveal the tissue, cellular, and molecular predictors leading to the
      development of chronic obstructive pulmonary disease (COPD) in smokers on the
      basis of a morphometric analysis of bronchial biopsy specimens. MATERIALS AND
      METHODS: A cross-sectional study was conducted in 115 smokers aged 40 to 60 years
      (58.3+/-3.24 years) with a male predominance of 90.9%. Morphological examination
      of bronchial biopsy specimens was first made in the smoking patients with and
      without COPD. RESULTS: The smokers with COPD versus those without this condition
      were found to have a statistically significant increase in a number of
      indicators: the specific volume (SV) of the surface epithelium (p=0.017), SV of
      basal epitheliocytes (p=0.008), the height of the epithelium (p=0.001), and the
      thickness of the basal membrane (p=0.006) due to impaired regeneration processes
      in the bronchial epithelium and to fibrosis of the lamina propria of the bronchi
      with a concurrent increase in the total number of fibroblasts. The group of
      smokers with COPD, unlike the comparison group, showed signs of vascular
      remodeling and microcirculatory disorders as the increased connective tissue
      volumetric density of the lamina propria of the bronchi with predominant
      perivascular localization. This was followed by reductions in the relative volume
      of capillaries (p=0.016), in the SV of micropinocytic vesicles (p=0.005), and the
      size of Weibel-Palade bodies (p=0.004) in the endotheliocytes. In the COPD
      patients, the total density of cell infiltrate per mm2 of the lamina propria of
      the bronchi was statistically significantly (p<0.001) greater than that in the
      comparison group at the expense of neutrophils, lowly and moderately granulated
      basophils, macrophages, plasma cells with a simultaneous rise in their
      interepithelial forms. CONCLUSION: Compensatory structural changes without signs
      of bronchial wall remodeling were recorded in the smokers without signs of
      bronchial disease. The smokers with the examined nosological entity were observed
      to have morphological signs of hemodynamic disorders, as well as perivascular
      fibrosis, atrophy, and squamous cell metaplasia of the bronchial epithelial
      lining.

PMID- 27030325
TI  - [Nebulized budesonide in the treatment of exacerbations of chronic obstructive
      pulmonary disease: Efficacy, safety, and effects on the serum levels of soluble
      differentiation molecules].
AB  - AIM: To investigate the efficacy and safety of nebulized budesonide and systemic
      glucocorticosteroids (GCS) (SGCS) in the treatment of an exacerbation of chronic
      obstructive pulmonary disease (COPD) and their effects on the serum concentration
      of soluble leukocyte differentiation antigens. MATERIALS AND METHODS: Seventy
      eight hospitalized patients with an acute exacerbation of COPD were randomized
      into two groups: 1) 37 patients took nebulized budesonide 4 mg/day; 2) 41
      patients received intravenous prednisolone. The symptoms of COPD, forced
      expiratory volume in one second (FEV1) and other spirometric indicators,
      peripheral blood oxygen saturation (SpO2), and adverse events were studied. The
      serum levels of the soluble adhesion molecules CD50 (sCD50) and CD54 (sCD54) and
      the lymphocyte activation molecules CD38 (sCD38) and CD25 (sCD25) were
      investigated by an enzyme immunoassay. RESULTS: There was a significant
      resolution of the symptoms of COPD, FEV1, and SpO2 in both groups after
      treatment. The incidence of hyperglycemia episodes was lower in the budesonide
      group than in the sGCS group. GCSs caused a decrease in the serum level of
      soluble interleukin-2 receptor (sCD25) in both groups. A prednisolone cycle,
      unlike a budesonide one, was found to reduce the concentrations of sCD54, sCD50,
      and sCD38. CONCLUSION: Nebulized budesonide is an effective and safe alternative
      to SGCS in treating an exacerbation of COPD. Inhaled GCSs, unlike SGCSs, exhibit
      anti-inflammatory activity, but exert no immunosuppressive activity.

PMID- 27030326
TI  - [Pathogenetic effects of low-intensity laser therapy for chronic obstructive
      pulmonary disease].
AB  - AIM: To study the impact of low-intensity laser therapy (LILT) on typical
      pathological processes of impairments in platelet aggregation and
      microcirculation (MC) in patients with chronic obstructive pulmonary disease
      (COPD). MATERIALS AND METHODS: A photo optical aggregatometric method was used to
      investigate platelet aggregation function in patients with COPD and MC was
      estimated by laser Doppler flowmetry over time. RESULTS: There were
      muitidirectional changes in platelet aggregation function with a predominance of
      hyperaggregation, as well as a significant improvement in aggregation indicators
      during LILT; the latter was shown to have a correcting impact on MC disorders in
      patients with COPD in the presence of the spastic and stagnant-stasic types of
      MC, which were prevalent in the majority of patients. CONCLUSION: Laser therapy
      used in the combination treatment of patients with COPD promotes correction of
      the typical pathological processes.

PMID- 27030327
TI  - [Clinical manifestations of asthma during combination therapy using
      ceruloplasmin].
AB  - AIM: To estimate the time course of clinical changes in patients with asthma
      during combination therapy using ceruloplasmin (CP). MATERIALS AND METHODS: A
      total of 92 asthmatic patients were examined. Their medical history data were
      collected; external lung function testing and clinical, laboratory, and
      instrumental examinations, involving the determination of the indicators of lipid
      peroxidation (LPO) (malonic dialdehyde (MDA), methemoglobin, carboxyhemoglobin)
      and the antioxidant system (superoxide dismutase (COD), sulfhydryl groups), were
      performed in all the patients over time. According to the therapy used, the
      patients were divided into 2 groups matched for gender, age, and clinical
      manifestations of the disease. A study group consisted of 45 patients who took CP
      in addition to conventional therapy. A comparison group included 47 patients
      receiving standard therapy. RESULTS: During the combination therapy using CP, the
      asthmatic patients showed a reduction in the elevated concentrations of MDA,
      methemoglobin, and carboxyhemoglobin and increases in the activity of COD and in
      the levels of sulfhydryl groups, which was followed by a considerable clinical
      improvement. During the conventional therapy, the indicators of LPO remained high
      and those of the antioxidant system did low, suggesting permanent oxidative
      stress. CONCLUSION: CP incorporation into the combination therapy of asthmatic
      patients contributes to elimination of prooxidant-antioxidant imbalance, which is
      followed by a marked positive clinical effect.

PMID- 27030328
TI  - [Functional and laboratory characteristics in the concomitance of asthma and
      obesity at a young age].
AB  - AIM: To study the peripheral blood level of leptin and adiponectin and their
      possible effect on the functional status of the respiratory system in young
      asthmatic patients in relation to body mass index (BMI) for the optimization of
      asthma therapy. MATERIALS AND METHODS: Examinations were made in 133 people,
      including a study group of 93 patients with asthma who were divided into 2 groups
      according to BMI: 1) those with a BMI of less 25 kg/m2 and 2) those with a BMI of
      30 kg/m2 or more, as well as a control group of 40 apparently healthy patients.
      The investigators studied external respiratory function (ERF), the peripheral
      blood levels of leptin and adiponectin, the biochemical composition of plasma, by
      determining total cholesterol, high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, and triglycerides. RESULTS: Lipid metabolic disorders as
      dyslipidemia and hypercholesterolemia, increased severity of disease, and
      decreased ERF were recorded in the concomitance of obesity and asthma. The
      peripheral blood level of leptin in young asthmatic patients with obesity was
      found to be associated with higher BMI. CONCLUSION: A more severe course of
      disease presenting with decreased ERF, impaired lipid metabolism, and elevated
      peripheral blood leptin levels were noted in the concomitance of asthma and
      obesity at a young age.

PMID- 27030329
TI  - [Association of decreased external pulmonary function with cognitive
      impairments].
AB  - AIM: To examine the association between the basic indicators of external
      respiratory function (ERF) and cognitive impairments (CIs). MATERIALS AND
      METHODS: The materials of a population-based cross-sectional study were used in
      the investigation; a representative sample consisted of 3818 men and women aged
      45-69 years. Forced expiratory volume in the first second (FEV1), the ratio of
      FEV1 to forced vital capacity (FVC) were determined to assess ERF. CIs were
      evaluated using the 10-word test described by A.R. Luria, Cog-sum indices (the
      sum of correctly reproduced words with 3 attempts), and Cog-mean=Cog-sum/3.
      RESULTS: In patients with an FEV1/FVC <70%, the probability of a Cog-sum of <20
      scores was twice higher than in those with an FEV1/FVC >=70%; in patients with an
      FEV1 <80%, the probability of a Cog-sum of <20 scores was also 2 times higher
      than in those with an FEV1 >=80%. Multiple regression analysis revealed no
      significant associations between Cog-sum index and smoking index, body mass
      index, and blood pressure. Cog-sum was inversely related to age and directly
      related to FEV1 and female sex. Binary logistic regression analysis showed that
      gender, age, and FEV1 were statistically significant variables. The relative risk
      of a Cog-sum of <20 that was 1.7 times higher in the men than in the women, 1.8
      times higher in the patients with an FEV1 <80% than in those with an FEV1 >=80%
      (model 1), 1.7 times higher in the patients with an FEV1/FVC <70% than in those
      with FEV1/FVC >=70% (model 2) increased with age. CONCLUSION: The decrease in the
      basic indicators of ERF (FEV1, FEV1/FVC) is an independent predictor of CIs.

PMID- 27030330
TI  - [Current characteristics of all-cause and circulatory disease mortality in the
      Azerbaijan Republic].
AB  - AIM: To prove the value of summary data from the State Statistics Commission to
      characterize of risk of death from circulatory system diseases (CSD). MATERIAL
      AND METHODS: The official data of the State Statistics Commission of the
      Azerbaijan Republic, which are available at its website (www.stat.gov.az), were
      analyzed using descriptive statistical procedures to identify qualitative signs.
      RESULTS: The population-level CSD death rates in 2011-2013 ranged from 362.7 to
      379.60/0000, amounting to 61.1-63.8% of the all-cause mortality in the
      population. There were definite differences in male and female deaths due to CSD
      (377.2-392.0 and 348.4-367.40/0000) and in its proportion among all-cause
      mortality rates (58.4-60.5 and 64.1-66.4%). The death rates from CSD in the urban
      (361.1-380.80/0000) and rural (364.5-378.30/0000) populations and its proportion
      among all-cause mortality rates in these populations (60.6-62.7 and 61.6-62.8%)
      were similar. The male and female working-age population showed essentially
      dissimilar CSD mortality rates (169.2-179.8 and 51.8-57.10/0000), the men being
      at greater risk of death (3.14-3.27). The ratio of all-cause mortality rates in
      the male and female working-age populations (2.62-2.67) differed from that of CSD
      specific ones in these populations (3.14-3.27). There was a slight difference in
      CSD-specific mortality rates in the urban and rural working-age populations
      (116.1-125.0 and 104.9-114.70/0000). There was also evidence for their similarity
      in the proportion of CSD among the all-cause mortality rates (43.2-46.2 and 45.0
      49.6%). CONCLUSION: The existing characteristics of mortality in the population
      (a growth tendency due to CSD) suggest the priority of preventing these diseases.

PMID- 27030331
TI  - [The role of immune factors in the progression of chronic kidney diseases in HIV
      infection].
AB  - AIM: To determine the significance of immune factors in the pathogenesis of
      kidney injuries in HIV infection, by investigating the cellular and cytokine
      components of an immune response. MATERIALS AND METHODS: Thirty HIV-infected
      patients (mean age 31.7+/-6.2 years) with chronic kidney disease (CKD) were
      examined. A comparison group consisted of 10 HIV-infected patients without signs
      of kidney injury. A control group included 24 healthy individuals to analyze
      immune status and 15 people to estimate the normal values of the cytokine
      composition. The cellular composition of lymphocytes on a typical immunogram was
      determined on a flow cytofluorometer; the serum concentrations of cytokines were
      measured on a multichannel photometer. RESULTS: The HIV-infected patients with
      kidney injury displayed significant reductions in the absolute (0.2.109/l and
      0.4.109/l, respectively; r=0.015) and relative (14.75 and 22%, respectively;
      r=0.005) counts of CD3+/CD4+ cells and in the immunoregulatory index (0.2 and
      0.4, respectively; r=0.014) as compared to those in HIV-infected patients without
      kidney disease (r<=0.05) with a rise in the number of cytotoxic T cells
      (CD3+/CD8+). The HIV-infected patients showed a preponderance of
      immunosuppressive cytokine compositions, as indicated by the high levels of
      transforming growth factor-beta (a more than 50-fold increase) and by a
      statistically significant rise in the level of tumor necrosis factor-alpha (TNF
      alpha) (with CD4+ lymphocyte counts more or less than 200 cells/ul - 19.0 and
      24.2 pg/ml, respectively; p=0.017; with HIV RNA levels more and less than 100,000
      copies/ml - 24.4 and 19.7 pg/ml, respectively; p=0.012). CONCLUSION: The HIV
      infected patients with CKD developed kidney injury in the presence of a more
      pronounced decrease in blood T helper lymphocyte subpopulation levels with a
      predominance of proinflammatory and immunosuppressive responses. TNF-alpha in
      combination with immunosuppression and high viral loads was established to play a
      leading role in the development of kidney injury in HIV infection.

PMID- 27030332
TI  - [Resistance to protease inhibitors and efficiency of antiviral therapy in
      patients with chronic hepatitis C].
AB  - AIM: To clarify the role of virus resistance in the efficiency of antiviral
      therapy with protease inhibitors (PIs) chronic hepatitis C (CHC) patients, with
      moderate sensitivity to interferon-alpha. MATERIALS AND METHODS: Eight Caucasian
      patients (4 men and 4 women) aged 21 to 65 years (median 52.5 years) with
      genotype 1b hepatitis C virus (HCV) infection were included in the study. Two
      patients were diagnosed with liver cirrhosis; 4 had been ineffectively treated
      with peginterferon in combination with ribavirin. None of the patients had
      obesity and/or insulin resistance. All the 8 patients received triple therapy
      with PIs (boceprevir (n=3), telaprevir (n=4), and simeprevir (n=1)) and as a
      result failed to achieve a sustained virologic response. All the participants
      were studied to identify mutations in HCV NS3/4A region. RESULTS: Five of the 8
      patients were found to have mutations in HCV NS3/4A region (substantially
      reducing drug susceptibility in 3 cases). CONCLUSION: In CHC patients who are
      moderately sensitive to interferon-alpha and receive therapy with PIs, resistance
      to the latter is critically important for the efficiency of therapy and the
      timely identification of resistance mutations can contribute to the choice of an
      optimal treatment policy.

PMID- 27030333
TI  - [Possible influence of epidemiological risk factors on the development of
      urolithiasis].
AB  - AIM: To study the epidemiological factors participating in the development of
      urolithiasis as risk factors. MATERIALS AND METHODS: The results of the 2007-2011
      examinations and follow-ups of 2305 patients diagnosed with urolithiasis, who had
      been treated at the bases of the Department of Urology, Azerbaijan Medical
      University, at the Acad. M.A. Mirkasimov Republican Clinical Hospital, and at the
      central hospitals in the North and North West regions of the Republic of
      Azerbaijan, were analyzed. RESULTS: In most cases, the 16-30- and 41-50-year age
      groups were at high risk for urolithiasis; an association was found between body
      mass index and the development of this disease. The mineral salt composition of
      stones was characterized by oxalate content in the majority of cases; urates
      ranked second. Urolithiasis was considered to be predominantly related to poor
      and satisfactory living conditions in most cases. Calculogensis in urolithiasis
      was most common in the people who had sedentary jobs, or in the unemployed.
      Examining the association of calculogenesis in urolithiasis patients with their
      geographical site type showed that the majority of these patients lived in the
      rural areas. CONCLUSION: The males who are older, overweight, lead a sedentary
      lifestyle or are unemployed, specifically those who live in the rural area, must
      more carefully implement preventive measures.

PMID- 27030334
TI  - [Effect of Remaxol on the efficiency of standard treatment for infiltrative
      pulmonary tuberculosis].
AB  - AIM: To investigate the effect of Remaxol on the efficiency of standard treatment
      in patients with infiltrative pulmonary tuberculosis (IPT). MATERIALS AND
      METHODS: The results of treatment were analyzed in 90 patients with new-onset IPT
      in the phase of decay who received basic tuberculosis treatment regimens I, IIb,
      and IV. In addition, a study group of 45 patients used dropwise intravenous
      Remaxol 400 ml daily and a control group 45 patients had dropwise intravenous 5%
      glucose solution 400 ml daily. All the patients underwent clinical, laboratory
      and instrumental (X-ray) examinations over time. RESULTS: The incorporation of
      remaxol into the combination treatment of IPT enhanced the efficiency of therapy,
      which manifested as reductions in the hepatotoxicity of etiotropic drugs and in
      the degree of dysproteinemia and as accelerated destructive regression in
      tuberculous infiltrates with a subsequent decrease in the need for
      phthisiosurgical care. Remaxol included into the standard complex treatment
      regimens for IPT contributed to the rapider normalization of laboratory
      parameters of the liver and to the accelerated regression of destructive changes
      in the tuberculous infiltrates. CONCLUSION: Incorporation of remaxol into the
      combination treatment of patients with IPT enhances the efficiency of its
      therapy, promotes the rapider normalization of laboratory indices of the liver
      and the accelerated regression of destructive changes in tuberculous infiltrates,
      which reduces the need for phthisiosurgical care.

PMID- 27030335
TI  - [Population characteristics of metabolic syndrome components in 25-64-year-old
      males of an average urbanized Siberian town].
AB  - AIM: To establish the population characteristics of the components of metabolic
      syndrome (MS) in the age range of 25-64-year-old males in an average urbanized
      Siberian town. MATERIALS AND METHODS: A cross-sectional epidemiological survey
      was conducted in a representative sample of the electorate of a Tyumen
      administrative district among 1000 males, with 250 being in each of 4 life
      decades (25-34, 35-44, 45-54, and 55-64 years). There were 850 (85%) responses.
      The IDF criteria (2005) were used to evaluate MS. RESULTS: In the Tyumen open
      population of 25-64-year-old men, the population characteristics of systolic
      blood pressure (BP) and waist circumference (WC) were shifted to the right in the
      normal distribution range, which determined the high prevalence of hypertension
      and abdominal obesity (AO). In the 25-64-year-old men with the high prevalence of
      hypertension (a standardized rate of 59.8%) and AO (a standardized rate of
      42.6%), the age was positively related to systolic BP in the third to fifth
      decades of life, diastolic BP, and WC at all ages. CONCLUSION: Examining the
      epidemiological situation regarding the prevalence of MS components necessitates
      the elaboration of a scientifically sound prevention program in the specific
      conditions of an average urbanized Siberian town.

PMID- 27030336
TI  - [Recurrent tracheal papillomatosis concurrent with asthma].
AB  - A thorough collection of complaints and history data, physical examination, and
      lung function tests are necessary to confirm the diagnosis of asthma. The latter
      must be differentiated from different diseases in the majority of patients
      according to age. Recurrent respiratory papillomatosis is caused by human
      papillomavirus and involves mainly the upper respiratory tract. The paper
      describes a case of tracheal papillomatosis concurrent with atopic asthma. 

PMID- 27030337
TI  - [Coexistence of pulmonary sarcoidosis and primary Sjogren's syndrome].
AB  - The paper describes a case of a rare coexistence of primary Sjogren's syndrome
      (PSS) and sarcoidosis in a 41-year-old female with histologically verified lung
      and locomotor system diseases and keratoconjunctivitis sicca. PSS was diagnosed
      based on the 2012 ACR classification criteria, in the framework of which
      serological, histological, and gland function tests and instrumental diagnostic
      methods were performed. The diagnosis of sarcoidosis was based on clinical,
      radiographic, and histological findings. 

PMID- 27030338
TI  - [Choice of an antihistamine administration route in the treatment of allergic
      diseases].
AB  - Allergic diseases (AD) are an interdisciplinary problem in practical health care
      and characterized by high prevalence, severity, and huge financial costs of their
      treatment, prevention, and rehabilitation in patients. In this connection,
      control of allergy symptoms attracts the meticulous attention of physicians of
      all specialties. The efficiency of pharmacotherapy in clinical practice
      frequently depends not only on what medication, but also what mode of its
      delivery (administration) is used. Clinicians are well aware of the fact that
      oral administration of some drugs, antihistamines in particular, may be lowly
      effective or ineffective and their parenteral route gives rise to their
      sufficient clinical effect. This communication presents for general practitioners
      a pathogenetic rationale for prescribing histamines and indications for their
      parenteral administration in AD. 

PMID- 27030339
TI  - A protocol for management of blood loss in surgical treatment of peritoneal
      malignancy by cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy.
AB  - BACKGROUND AND AIMS: The treatment of peritoneal malignancies with cytoreductive
      surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has
      been shown to be associated with massive surgical blood loss. Maintaining high
      fibrinogen levels throughout surgery may reduce blood loss in these patients. The
      primary aim of the study was to see if Tranexamic Acid (TXA) and cryoprecipitate
      reduced surgical blood loss and hence red cell transfusions. A comparison was
      made with a cohort of patients treated with fresh frozen plasma (FFP) alone. The
      secondary aim was to measure the effect of both protocols on coagulation
      parameters and the incidence of arterial or venous thrombosis. METHOD: We used
      prospectively collected data from 201 patients who had complete CRS with HIPEC
      for peritoneal malignancy using different protocols during two discrete 12-month
      time periods. RESULTS: The new transfusion protocol led to a higher average
      fibrinogen level intra-operatively and post-operatively, with a significant
      reduction in average RBC, FFP and platelet transfusion intra-operatively per
      patient from 4.2 to 1.8 units, 6.2 to 0.2 units and 0.1 to 0 units, respectively.
      No significant difference in PT or APTT was seen between patients treated with
      the standard and new protocols. Venous thrombosis occurred in seven patients
      treated with the standard protocol and five with the new protocol. A single case
      of arterial thrombosis was seen in both groups. CONCLUSION: Patients treated with
      upfront TXA and cryoprecipitate during CRS required less RBC transfusion than
      those treated with the standard protocol of early FFP.

PMID- 27030340
TI  - Statin and Aspirin Use Among Hispanic and Latino Adults at High Cardiovascular
      Risk: Findings From the Hispanic Community Health Study/Study of Latinos.
AB  - BACKGROUND: Despite variations in the prevalence of cardiovascular disease and
      related risk factors among US Hispanic/Latino adults of diverse backgrounds,
      there is little information on whether disparities exist in the use of
      medications for the primary and secondary prevention of cardiovascular disease.
      We examined the prevalence of statin and aspirin use among diverse US
      Hispanic/Latino adults at high cardiovascular risk. METHODS AND RESULTS: A
      multicenter population-based study, the Hispanic Community Health Study/Study Of
      Latinos, included a total of 16 415 participants of Mexican, Puerto Rican, Cuban,
      Dominican, South American, and Central American backgrounds who were aged 18 to
      74 years and enrolled between March 2008 and June 2011. Our analyses were limited
      to 4139 participants considered to be at high cardiovascular risk. Age-adjusted
      prevalence of statin and aspirin use was 25% and 44%, respectively, overall but
      varied by Hispanic/Latino background among those at high cardiovascular risk;
      statin use was significantly higher (P<0.001) among adults of Puerto Rican (33%)
      and Dominican (28%) backgrounds compared with adults of other backgrounds
      (Mexican, 24%; Cuban, 22%; Central American, 20%; South American, 22%). There was
      no difference in aspirin use. After adjusting for health insurance coverage, the
      difference in prevalence of statin use was substantially reduced among
      participants with a Puerto Rican background, from an odds ratio of 1.73 (95% CI
      1.30-2.31) to 1.30 (95% CI 0.97-1.75), and with a Dominican background, from an
      odds ratio of 1.45 (95% CI 1.04-2.02) to 1.07 (95% CI 0.75-1.52), in comparison
      to their counterparts. CONCLUSIONS: Among Hispanic/Latino adults of diverse
      backgrounds, statin use was more prevalent among adults with Puerto Rican and
      Dominican backgrounds at high cardiovascular risk. These differences in statin
      use were explained, in part, by differences in insurance coverage. These findings
      have important implications for the prevention of disparities in cardiovascular
      outcomes within the growing US Hispanic/Latino population.

PMID- 27030342
TI  - Defying, producing, and overlooking stereotypes? The complexities of mobilizing
      "grandmotherhood" as political strategy.
AB  - This article explores the Canadian Grandmothers to Grandmothers Campaign, a
      mobilization of older women responding to the effects of HIV/AIDS in sub-Saharan
      Africa. Based on interviews, participant observation, and archival work, this
      article looks at how and to what effect "grandmotherhood," as discourse, was
      mobilized and deployed, in fluid and fractured ways, in order to increase
      members' credibility as global social justice actors and build their solidarity
      with African women. These mobilizations functioned to uphold essentialist notions
      of what being a grandmother means, while also challenging stereotypes of older
      women as frail and disengaged. 

PMID- 27030343
TI  - [Happy birthday, Rivista di psichiatria!].

PMID- 27030341
TI  - Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary
      for cell reprogramming.
AB  - During the process of reprogramming to induced pluripotent stem (iPS) cells,
      somatic cells switch from oxidative to glycolytic metabolism, a transition
      associated with profound mitochondrial reorganization. Neither the importance of
      mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms
      controlling this process are well understood. Here, we show that an early wave of
      mitochondrial fragmentation occurs upon expression of reprogramming factors.
      Reprogramming-induced mitochondrial fission is associated with a minor decrease
      in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is
      phosphorylated early in reprogramming, and its knockdown and inhibition impairs
      both mitochondrial fragmentation and generation of iPS cell colonies. Drp1
      phosphorylation depends on Erk activation in early reprogramming, which occurs,
      at least in part, due to downregulation of the MAP kinase phosphatase Dusp6.
      Taken together, our data indicate that mitochondrial fission controlled by an Erk
      Drp1 axis constitutes an early and necessary step in the reprogramming process to
      pluripotency. 

PMID- 27030344
TI  - Post-rationalist psychotherapy academy today:research and clinical practice.
AB  - The post-rationalist psychotherapy academy (non-classic cognitive approach)
      started at the end of the 80's with a series of consistent hypotheses. It is an
      academy which stems from contemporary psychotherapy and develops different areas,
      giving a strong contribution to theoretical and clinical psychotherapy. This
      academy has presented development as all other psychotherapy schools have, as
      well as the same difficulties and solutions. In this article, our aim is to show
      some tendencies that don't present an epistemological, theoretical,
      methodological and coherency, since these tendencies don't allow any confutation,
      which is the fundamental premise of Vittorio Guidano's academy. Finally, we
      stress how it's nowadays crucial in psychotherapy, to apply coherent
      methodological and conceptual positions based on the research.

PMID- 27030345
TI  - [Psychotherapy of borderline personality disorder: critical factors and proposals
      of intervention].
AB  - Borderline personality disorder (BPD) represents a significant therapeutic
      challenge. Critical factors in psychotherapeutic treatment of patients with BPD
      are noticeable and strictly related to the psychopathological dimensions of this
      disorder: affective and relational instability, behavioral impulsivity and
      precarious definition of identity. These features are emphasized by therapeutic
      intervention and become evident during the course of the treatment.
      Psychotherapeutic setting induces BPD patient to actualize the dysfunctional
      relational patterns that have been acquired during childhood. Specific critical
      factors concern the characteristics of the patient (risk of suicide, aggressive
      behaviors, chronic course of the disorder, disorganized attachment style), of the
      therapist (therapeutic skills, training, countertransference, risk of burnout)
      and of the setting of psychotherapy (patients selection, therapeutic alliance,
      need to set limits, duration and end of therapy). In Otto Kernberg's and Marsha
      Linehan's models of psychotherapy specific for DBP the authors identify
      substantially overlapping objectives and modalities of intervention. In
      particular, therapists should take care of patient safety, maintain boundaries of
      therapeutic setting and promote the development of psychotherapeutic process. The
      aim of this article is to analyze the main critical factors affecting
      psychotherapeutic process in patients with BPD. Objectives and priorities that
      therapist should consider to address these issues will be discussed. We will also
      try to make clear why interpersonal psychotherapy adapted to DBP can represent
      one of the therapeutic models that may be useful to manage and resolve these
      difficulties. 

PMID- 27030346
TI  - Theory of Mind and social functioning in schizophrenia: correlation with
      figurative language abnormalities, clinical symptoms and general intelligence.
AB  - AIM: Over past few decades, studies displayed Theory of Mind (ToM) as a system,
      including cognitive and affective features, rather than an unitary process.
      Within domains defining social cognition, ToM stands for the best predictor of
      poor social functioning in schizophrenia. The current study aimed to explore
      competence in ToM tasks, in metaphorical and idiomatic language identification
      tasks and in a conversational rules observance test, as well as relationship with
      social functioning, in a group of outpatients suffering from schizophrenia.
      METHODS.: 30 outpatients diagnosed with schizophrenia and 24 healthy subjects
      have been recruited. Both groups underwent TIB as premorbid IQ evaluation, PANSS,
      Theory of Mind Picture Sequencing Task, a metaphors and idiomatic expressions
      comprehension test and a conversational test. Social functioning was assessed
      with PSP. Results.Mean values of premorbid IQ showed no significant difference
      between patients and control group. In ToM and pragmatic competence tasks,
      differences between groups resulted in high significance, due to patients' lower
      performance. A correlation between metaphors and idiomatic expressions
      comprehension and second order false beliefs was detected. PSP showed a
      correlation with PANSS and cognitive-ToM, whereas leaving aside affective-ToM.
      CONCLUSIONS: Results showed how people affected with schizophrenia, in stable
      clinical condition, do have clear impairments in ToM and figurative language
      comprehension assignments. In our theoretical framework, correlation arisen
      between cognitive-ToM, pragmatic deficits, clinical status and social functioning
      level suggests usefulness of rehabilitative interventions to recover
      metacognitive functions and pragmatic abilities, in order to reduce social
      disability in schizophrenia.

PMID- 27030347
TI  - Psychopathology, psychosocial factors and obesity.
AB  - AIMS: The aims of this study were to evaluate the association between obesity and
      socio-demographic and psychopathological variables in a clinical sample of
      patients referred to a center for the diagnosis and treatment of obesity,
      compared with a homogeneous sample of normal-weight subjects. METHODS: In the
      context of a research project regarding obesity and psychopathology, a
      multivariate logistic regression analysis was used to examine the association
      between obesity and the demographic and clinical variables, on the basis of the
      dataset of a consecutive sample of 293 obese patients (48 males, 245 females,
      mean age: 45.41+/-13.55, mean body mass index [BMI] 35.6+/-6.2)compared with a
      control group of 293 non-obese subjects (48 males, 245 females, mean age 45.66+/
      13.86, mean BMI 21.8+/-2.06). All subjects were assessed by structured clinical
      interview, the Structured Clinical Interview for Diagnosis for axis I DSM-IV
      (SCID-I) and for axis II DSM-IV(SCID-II). RESULTS: Multivariate statistical
      analysis showed that the status of housewife and the presence of lifetime axis I
      and II psychiatric diagnosis in general, and of depressive, anxiety, eating and
      some personality disorders in particular, significantly increased the likelihood
      of being overweight/obese. The likelihood for different combinations of risk
      factors increased from a value of 32.3% for an individual not exposed to any risk
      factor, to a value of 86.7% for those exposed to all risk factors considered.
      CONCLUSIONS: The presence of an axis I and/or II diagnosis and housewife status
      are both independently associated with an increased likelihood of being
      overweight/obese. The interaction of these factors increases this likelihood.
      Even taking into account the limits of the study, in particular of its cross
      sectional nature, these findings may have important implications in both
      prevention and treatment of obesity.

PMID- 27030349
TI  - [Not Available].

PMID- 27030348
TI  - The metabolic syndrome in an Italian psychiatric sample: a retrospective chart
      review of inpatients treated with antipsychotics.
AB  - INTRODUCTION: The metabolic syndrome (MS) is an area of interest for mental
      health research because individuals with mental illnesses have an increased risk
      of medical morbidity and mortality compared with the general population. This
      cross-sectional study is aimed to estimate the prevalence of metabolic syndrome
      in an Italian psychiatric sample, treated with different types of antipsychotics.
      METHODS: The data were derived from medical records of patient with affective and
      non-affective psychosis, admitted to the Hospital of L'Aquila psychiatric ward,
      from January 2012 to July 2014. The sample refers to consecutive admissions of
      subjects of both sexes, aged over 18 years, receiving one or more antipsychotic
      treatment. The diagnosis of MS was established when the clinical subject at least
      three of the five diagnostic criteria of the Adult Treatment Panel (NCEP-ATP III)
      were met. RESULTS: 389 subjects were evaluated. We report a MS prevalence of
      27.5%. This figure is very close to the metabolic syndrome prevalence in the
      Italian general population quoted around 26%. The BMI values also are very
      similar in these two populations, despite a higher obesity rate in the clinical
      sample. The MS prevalence rates in subject with schizophrenia, bipolar disorders
      and depressive disorders were respectively 30.6%, 36.4% and 36.8%. No significant
      differences in MS, diabetes or dyslipidemia rates were found among the three
      diagnostic groups. We did not find differences in metabolic syndrome prevalence
      either in relation to psychotropic polypharmacy or in relation to typical or
      atypical antipsychotics. However the psychiatric females in the clinical sample
      tend to have higher obesity rate, with a sort of all or none distribution (i.e.
      more obesity, more normal weight, but less overweight) compared to the general
      population. CONCLUSIONS: These findings could be explained by the interaction of
      some sort of liability due to drug treatment, illness related lifestyles, gender
      and other interacting factors (e.g. genetic) with metabolic issues.

PMID- 27030350
TI  - Reasons for UK doctor's erasure are withheld on grounds of "confidentiality".

PMID- 27030351
TI  - A Mathematical Model of T1D Acceleration and Delay by Viral Infection.
AB  - Type 1 diabetes (T1D) is often triggered by a viral infection, but the T1D
      prevalence is rising among populations that have a lower exposure to viral
      infection. In an animal model of T1D, the NOD mouse, viral infection at different
      ages may either accelerate or delay disease depending on the age of infection and
      the type of virus. Viral infection may affect the progression of T1D via multiple
      mechanisms: triggering inflammation, bystander activation of self-reactive T
      cells, inducing a competitive immune response, or inducing a regulatory immune
      response. In this paper, we create mathematical models of the interaction of
      viral infection with T1D progression, incorporating each of these four
      mechanisms. Our goal is to understand how each viral mechanism interacts with the
      age of infection. The model predicts that each viral mechanism has a unique
      pattern of interaction with disease progression. Viral inflammation always
      accelerates disease, but the effect decreases with age of infection. Bystander
      activation has little effect at younger ages and actually decreases incidence at
      later ages while accelerating disease in mice that do get the disease. A
      competitive immune response to infection can decrease incidence at young ages and
      increase it at older ages, with the effect decreasing over time. Finally, an
      induced Treg response decreases incidence at any age of infection, but the effect
      decreases with age. Some of these patterns resemble those seen experimentally. 

PMID- 27030352
TI  - Effects of nutrition education on weight gain prevention: a randomized controlled
      trial.
AB  - BACKGROUND: Body weight (BW) reduction through energy restriction is ineffective
      at impacting the obesity epidemic. Shifting from an obesity treatment to weight
      gain prevention focus may be more effective in decreasing the burden of adult
      obesity. METHODS: This was a 1-year randomized controlled trial of weight gain
      prevention in healthy premenopausal women, aged 18-45 y, with a body mass index
      (BMI) of >18.5 kg/m(2). Eighty-seven women were randomized to a weight gain
      prevention intervention delivered by a registered dietitian (RDG) or counselor
      (CSG), or to a control (CON) group. Eighty-one women (mean +/- SD, age: 31.4 +/-
      8.1 y; BW: 76.1 +/- 19.0 kg; BMI: 27.9 +/- 6.8 kg/m(2)) completed baseline
      testing and were included in intention-to-treat analyses; anthropometric, blood
      pressure, dietary intake and physical activity measurements and biochemical
      markers of health were measured every three months. Data were analyzed using
      repeated measures ANCOVA, with significance at P < 0.01. RESULTS: Sixty-two
      percent of women met the weight gain prevention criteria (BW change within +/-3
      %) after one year; this did not differ by group assignment. Body fat % was lower
      in the RDG versus CSG and CON groups at all intervals (P < 0.001). Systolic blood
      pressure increased from month 6 to 9 and decreased from month 6 to 12 in the CON
      group (P < 0.001), with a significant group x time interaction (P < 0.01).
      Estimated carbohydrate intake (%) was higher in the RDG vs. CON group at month 9
      (P < 0.01); fat intake (%) was lower in the RDG vs. CON group and CSG vs. CON
      group at months 3 and 9, respectively (P < 0.01). Estimated fruit intake (svgs/d)
      was higher in the RDG vs. CON group at months 3, 6, 9 and 12 (P < 0.01), and non
      meat protein sources (svgs/d) was higher in the RDG vs. CSG and CON groups at
      month 3 (P < 0.001). Estimated energy, macronutrient and food group intakes did
      not change over time. CONCLUSIONS: A majority of all participants maintained BW
      over one year and were able to do so regardless of whether they received
      nutrition education. Additional studies that include a variety of clinical
      outcomes are needed to evaluate further aspects of nutrition education on weight
      gain prevention and health status over the long term.

PMID- 27030354
TI  - ATP-sensitive K(+) channels (Kir6.1/SUR1) regulate gap junctional coupling in
      cochlear-supporting cells.
AB  - Using the double whole-cell patch-clamp technique, we found that the absence of
      intracellular ATP led to gap junction uncoupling in cochlear-supporting Hensen
      cells. The uncoupling was observed as a progressive reduction of the gap
      junctional electrical conductance from a starting value of approximately 40 nS to
      less than 0.04 nS within 10-20 min. The conductance rundown was partly avoided by
      at least 3 mM ATP and completely suppressed by 5 mM ATP or 5'-adenylyl
      imidodiphosphate (AMP-PNP), the non-hydrolysable ATP analog, in the pipette
      filling solution, suggesting that ATP was needed as ligand and not as a
      hydrolysable energy supplier or substrate for enzymatic reactions. The effect of
      intracellular ATP was mimicked by the external application of barium, a
      nonselective blocker of inwardly rectifying K(+) (Kir) channels, and
      glibenclamide, an inhibitor of the ATP-sensitive Kir channels (KATP). Moreover a
      Ba(2+)-sensitive whole-cell inward current was observed in absence of internal
      ATP. We propose that the internal ATP kept the KATP channels in a closed state,
      thereby maintaining the gap junction coupling of Hensen cells. The immunostaining
      of guinea pig cochlear tissue revealed for the first time the expression of the
      KATP channel subunits Kir6.1 and SUR1 in Hensen cells and supported the proposed
      hypothesis. The results suggest that KATP channels, as regulator of the gap
      junction coupling in Hensen cells, could be the physiological link between the
      metabolic state of the supporting cells and K(+) recycling in the organ of Corti.

PMID- 27030355
TI  - Laparoscopic gastrectomy versus open gastrectomy for elderly patients with
      gastric cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: The objective of this study was to evaluate the feasibility, safety,
      and potential benefits of laparoscopic gastrectomy (LG) comparing with open
      gastrectomy (OG) in elderly population. METHODS: Studies comparing LG with OG for
      elderly population with gastric cancer, published between January 1994 and July
      2015, were identified in the PubMed, Embase, and ISI Web of Science databases.
      Operative outcomes (intraoperative blood loss, operative time, and the number of
      lymph nodes harvested) and postoperative outcomes (time to first ambulation, time
      to first flatus, time to first oral intake, postoperative hospital stay,
      postoperative morbidity) were included and analyzed. The Newcastle-Ottawa Scale
      was used to assess the quality of the pooled study. A funnel plot was used to
      evaluate the publication bias. RESULTS: Seven studies totaling 845 patients were
      included in the meta-analysis. LG in comparison to OG showed less intraoperative
      blood loss (weighted mean difference (WMD) -127.47; 95% confidence interval (CI) 
      202.79 to -52.16; P < 0.01), earlier time to first ambulation (WMD -2.07; 95% CI 
      2.84 to -1.30; P < 0.01), first flatus (WMD -1.04; 95% CI -1.45 to -0.63; P <
      0.01), and oral intake (WMD -0.94; 95% CI -1.11 to -0.77; P < 0.01),
      postoperative hospital stay (WMD -5.26; 95% CI -7.58 to -2.93; P < 0.01), lower
      overall postoperative complication rate (odd ratio (OR) 0.39; 95% CI 0.28 to
      0.55; P < 0.01), less surgical complications (OR 0.47; 95% CI 0.32 to 0.69; P <
      0.01), medical complication (OR 0.35; 95% CI 0.22 to 0.56; P < 0.01), incisional
      complication (OR 0.40; 95% CI 0.19 to 0.85; P = 0.02), and pulmonary infection
      (OR 0.49; 95% CI 0.26 to 0.93; P = 0.03). No significant differences were
      observed between LG and OG for the number of harvested lymph nodes. However, LG
      had longer operative times (WMD 15.73; 95% CI 6.23 to 25.23; P < 0.01).
      CONCLUSIONS: LG is a feasible and safe approach for elderly patients with gastric
      cancer. Compared with OG, LG has less blood loss, faster postoperative recovery,
      and reduced postoperative morbidity.

PMID- 27030356
TI  - Regulatory T Cells in Post-stroke Immune Homeostasis.
AB  - The secondary neuroinflammatory response has come into focus of experimental
      stroke research. Immunological mechanisms after acute stroke are being
      investigated in the hope to identify novel and druggable pathways that contribute
      to secondary infarct growth after stroke. Among a variety of neuroimmunological
      events after acute brain ischemia, including microglial activation, brain
      leukocyte invasion, and secretion of pro-inflammatory factors, lymphocytes have
      been identified as the key leukocyte subpopulation driving the neuroinflammatory
      response and contributing to stroke outcome. Several studies have shown that pro
      inflammatory lymphocyte subpopulations worsen stroke outcome and that inhibiting
      their invasion to the injured brain is neuroprotective. In contrast to the
      effector functions of pro-inflammatory lymphocytes, regulatory T cells (Treg) are
      critically involved in maintaining immune homeostasis and have been characterized
      as disease-limiting protective cells in several inflammatory conditions,
      particularly in primary inflammatory diseases of the central nervous system
      (CNS). However, due to the complex function of regulatory cells in immune
      homeostasis and disease, divergent findings have been described for the role of
      Treg in stroke models. Emerging evidence suggests that this discrepancy arises
      from potentially differing functions of Treg depending on the predominant site of
      action within the neurovascular unit and the surrounding inflammatory milieu.
      This article will provide a comprehensive review of current findings on Treg in
      brain ischemia models and discuss potential reasons for the observed
      discrepancies.

PMID- 27030357
TI  - Perspectives on modelling the distribution of ticks for large areas: so far so
      good?
AB  - BACKGROUND: This paper aims to illustrate the steps needed to produce reliable
      correlative modelling for arthropod vectors, when process-driven models are
      unavailable. We use ticks as examples because of the (re)emerging interest in the
      pathogens they transmit. We argue that many scientific publications on the topic
      focus on: (i) the use of explanatory variables that do not adequately describe
      tick habitats; (ii) the automatic removal of variables causing internal
      (statistical) problems in the models without considering their ecological
      significance; and (iii) spatial pattern matching rather than niche mapping,
      therefore losing information that could be used in projections. METHODS: We focus
      on extracting information derived from modelling the environmental niche of
      ticks, as opposed to pattern matching exercises, as a first step in the process
      of identifying the ecological determinants of tick distributions. We perform
      models on widely reported species of ticks in Western Palaearctic to derive a set
      of covariates, describing the climate niche, reconstructing a Fourier
      transformation of remotely-sensed information. RESULTS: We demonstrate the
      importance of assembling ecological information that drives the distribution of
      ticks before undertaking any mapping exercise, from which this kind of
      information is lost. We also show how customised covariates are more relevant to
      tick ecology than the widely used set of "Bioclimatic Indicators" ("Biovars")
      derived from interpolated datasets, and provide programming scripts to easily
      calculate them. We demonstrate that standard pre-tailored vegetation categories
      also fail to describe tick habitats and are best used to describe absence rather
      than presence of ticks, but could be used in conjunction with the climate based
      suitability models. CONCLUSIONS: We stress the better performance of climatic
      covariates obtained from remotely sensed information as opposed to interpolated
      explanatory variables derived from ground measurements which are flawed with
      internal issues affecting modelling performance. Extracting ecological
      conclusions from modelling projections is necessary to gain information about the
      variables driving the distribution of arthropod vectors. Mapping exercises should
      be a secondary aim in the study of the distribution of health threatening
      arthropods.

PMID- 27030358
TI  - Clinical and imaging findings of progressive supranuclear palsy with predominant
      cerebellar ataxia.

PMID- 27030359
TI  - Regulatory modules controlling early shade avoidance response in maize seedlings.
AB  - BACKGROUND: Optimization of shade avoidance response (SAR) is crucial for
      enhancing crop yield in high-density planting conditions in modern agriculture,
      but a comprehensive study of the regulatory network of SAR is still lacking in
      monocot crops. RESULTS: In this study, the genome-wide early responses in maize
      seedlings to the simulated shade (low red/far-red ratio) and also to far-red
      light treatment were transcriptionally profiled. The two processes were
      predominantly mediated by phytochrome B and phytochrome A, respectively.
      Clustering of differentially transcribed genes (DTGs) along with functional
      enrichment analysis identified important biological processes regulated in
      response to both treatments. Co-expression network analysis identified two
      transcription factor modules as potentially pivotal regulators of SAR and de
      etiolation, respectively. A comprehensive cross-species comparison of orthologous
      DTG pairs between maize and Arabidopsis in SAR was also conducted, with emphasis
      on regulatory circuits controlling accelerated flowering and elongated growth,
      two physiological hallmarks of SAR. Moreover, it was found that the genome-wide
      distribution of DTGs in SAR and de-etiolation both biased toward the maize1
      subgenome, and this was associated with differential retention of various cis
      elements between the two subgenomes. CONCLUSIONS: The results provide the first
      transcriptional picture for the early dynamics of maize phytochrome signaling.
      Candidate genes with regulatory functions involved in maize shade avoidance
      response have been identified, offering a starting point for further functional
      genomics investigation of maize adaptation to heavily shaded field conditions.

PMID- 27030360
TI  - Targeting of tubulin polymerization and induction of mitotic blockage by Methyl 2
      (5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) in human
      cervical cancer HeLa cell.
AB  - BACKGROUND: Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine
      and vinca alkaloids are widely used in the treatment of various cancers. As with
      most chemotherapeutic agents, adverse effects and drug resistance are commonly
      associated with the clinical use of these agents. Methyl 2-(5-fluoro-2
      hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC), a benzimidazole
      derivative displays greater toxicity against various cancer compared to normal
      human cell lines. The present study, focused on the cytotoxic effects of MBIC
      against HeLa cervical cancer cells and possible actions on the microtubule
      assembly. METHODS: Apoptosis detection and cell-cycle assays were performed to
      determine the type of cell death and the phase of cell cycle arrest in HeLa
      cells. Tubulin polymerization assay and live-cell imaging were performed to
      visualize effects on the microtubule assembly in the presence of MBIC. Mitotic
      kinases and mitochondrial-dependent apoptotic proteins were evaluated by Western
      blot analysis. In addition, the synergistic effect of MBIC with low doses of
      selected chemotherapeutic actions were examined against the cancer cells.
      RESULTS: Results from the present study showed that following treatment with
      MBIC, the HeLa cells went into mitotic arrest comprising of multi-nucleation and
      unsegregated chromosomes with a prolonged G2-M phase. In addition, the HeLa cells
      showed signs of mitochondrial-dependant apoptotic features such as the release of
      cytochrome c and activation of caspases. MBIC markedly interferes with tubulin
      polymerization. Western blotting results indicated that MBIC affects mitotic
      regulatory machinery by up-regulating BubR1, Cyclin B1, CDK1 and down-regulation
      of Aurora B. In addition, MBIC displayed synergistic effect when given in
      combination with colchicine, nocodazole, paclitaxel and doxorubicin. CONCLUSION:
      Taken together, our study demonstrated the distinctive microtubule destabilizing
      effects of MBIC against cervical cancer cells in vitro. Besides that, MBIC
      exhibited synergistic effects with low doses of selected anticancer drugs and
      thus, may potentially reduce the toxicity and drug resistance to these agents.

PMID- 27030362
TI  - A Curious Distal Tibiofibular Neuropathic Fracture: A Case Report.
AB  - : Hindfoot and distal leg neuropathic fracture collapse secondary to normal
      pressure hydrocephalus is a very rare clinical pathology. The authors present a
      case of a 69-year-old woman who sustained a distal tibiofibular fracture that
      resulted in a recurvatum deformity with idiopathic neuropathy and gait
      instability on initial presentation. A subtalar and ankle joint arthrodesis was
      performed achieving rectus alignment of the lower extremity with no postoperative
      complications. Her neuropathic etiology was negative for common causative
      factors, including diabetes, infection, nutritional deficiencies, congenital
      neuropathy, and trauma. Approximately 6 months postoperatively, the patient had
      persistent bilateral lower extremity weakness with the sensation of her "feet
      sticking to the floor" on ambulation. A referral to neurology revealed a normal
      pressure hydrocephalus as a possible etiology for her gait abnormalities and
      neuropathy. She required a ventriculoperitoneal shunt, with resolved gait
      disturbance and associated weakness approximately 1.5 years postoperatively.
      LEVELS OF EVIDENCE: Therapeutic, Level IV: Case report.

PMID- 27030361
TI  - Microbial diversity in the floral nectar of Linaria vulgaris along an
      urbanization gradient.
AB  - BACKGROUND: Microbes are common inhabitants of floral nectar and are capable of
      influencing plant-pollinator interactions. All studies so far investigated
      microbial communities in floral nectar in plant populations that were located in
      natural environments, but nothing is known about these communities in nectar of
      plants inhabiting urban environments. However, at least some microbes are
      vectored into floral nectar by pollinators, and because urbanization can have a
      profound impact on pollinator communities and plant-pollinator interactions, it
      can be expected that it affects nectar microbes as well. To test this hypothesis,
      we related microbial diversity in floral nectar to the degree of urbanization in
      the late-flowering plant Linaria vulgaris. Floral nectar was collected from
      twenty populations along an urbanization gradient and culturable bacteria and
      yeasts were isolated and identified by partially sequencing the genes coding for
      small and large ribosome subunits, respectively. RESULTS: A total of seven yeast
      and 13 bacterial operational taxonomic units (OTUs) were found at 3 and 1%
      sequence dissimilarity cut-offs, respectively. In agreement with previous
      studies, Metschnikowia reukaufii and M. gruessi were the main yeast constituents
      of nectar yeast communities, whereas Acinetobacter nectaris and Rosenbergiella
      epipactidis were the most frequently found bacterial species. Microbial incidence
      was high and did not change along the investigated urbanization gradient.
      However, microbial communities showed a nested subset structure, indicating that
      species-poor communities were a subset of species-rich communities. CONCLUSIONS:
      The level of urbanization was putatively identified as an important driver of
      nestedness, suggesting that environmental changes related to urbanization may
      impact microbial communities in floral nectar of plants growing in urban
      environments.

PMID- 27030363
TI  - The Reverse Ludloff Osteotomy for Bunionette Deformity.
AB  - Background The typical bunionette deformity often presents as pain over the
      lateral margin of the fifth metatarsal head. There have been numerous operative
      treatments described for this pathology. The purpose of this study was to
      evaluate the results after a reverse Ludloff osteotomy in cases of severe
      bunionette deformities. Methods Between 2008 and 2012, 16 patients received a
      reverse Ludloff osteotomy of the fifth metatarsal due to a symptomatic type II or
      III bunionette that failed nonoperative treatment. We retrospectively reviewed
      charts, radiographic images, postoperative AOFAS (American Orthopaedic Foot and
      Ankle Society) lesser toe scores, and the EQ-5D at a mean of 41.9 months (range,
      31-74 months) of follow-up. Additionally, limitation in activities of daily
      living, pain, and patient satisfaction were assessed. Results At latest follow
      up, the mean AOFAS lesser toe score was 86.6 points and the mean EQ-5D score was
      14.1. Fifteen patients had no or only little limitations. Fifteen out of 16
      patients were satisfied or predominantly satisfied. Radiographic analysis showed
      for type II deformities a correction of the lateral bowing from 8.1 degrees  down
      to 0.67 degrees  (P < .001). The fourth-fifth intermetatarsal angle (4-5 IMA)
      improved from a mean of 13.2 degrees  to a mean of 5.2 degrees  (P < .001). The
      length of the fifth metatarsal was unchanged (P > .05). There were no observed
      complications, and no revision was necessary. Conclusion In the present study,
      the reverse Ludloff osteotomy had a high satisfaction rate and no complications.
      It provided radiographic correction of the deformity and may be considered in the
      surgical treatment of severe bunionette deformities. LEVELS OF EVIDENCE:
      Therapeutic, Level IV: Case series.

PMID- 27030365
TI  - Minimizing antibody cross-reactivity in multiplex detection of biomarkers in
      paper-based point-of-care assays.
AB  - Highly multiplexed immunoassays could allow convenient screening of hundreds or
      thousands of protein biomarkers simultaneously in a clinical sample such as serum
      or plasma, potentially allowing improved diagnostic accuracy and clinical
      management of many conditions such as autoimmune disorders, infections, and
      several cancers. Currently, antibody microarray-based tests are limited in part
      due to cross reactivity from detection antibody reagents. Here we present a
      strategy that reduces the cross-reactivity between nanoparticle-bound reporter
      antibodies through the application of ultrasound energy. By this concept, it was
      possible to achieve a sensitivity 10(3)-fold (5 pg mL(-1)) lower than when no
      ultrasound was applied (50 ng mL(-1)) for the simultaneous detection of three
      different antigens. The detection limits and variability achieved with this
      technique rival those obtained with other types of multiplex sandwich assays. 

PMID- 27030364
TI  - A phase II trial of prophylactic olanzapine combined with palonosetron and
      dexamethasone for preventing nausea and vomiting induced by cisplatin.
AB  - AIM: To investigate the efficacy and safety of olanzapine in combination with
      palonosetron and dexamethasone for patients receiving cisplatin (>=50 mg/m(2) ),
      because this antiemetic therapy has not been sufficiently examined in patients
      receiving cisplatin. METHODS: We conducted a phase II study to evaluate the
      efficacy and safety of olanzapine in combination with palonosetron and
      dexamethasone for chemotherapy naive patients receiving cisplatin (>=50 mg/m(2)
      ). Patients received prophylactic dexamethasone (20 mg IV, day 1), palonosetron
      (0.75 mg IV, day 1), and olanzapine (10 mg, days 1-4). The patients were
      monitored for emesis and nausea for 120 h after chemotherapy. The primary
      endpoint was the complete response (CR) rate, which was defined as no vomiting
      episodes and no use of rescue medication for the overall period. CR rates of 65%
      and 45% would indicate the potential usefulness and the lower limit of interest,
      respectively. RESULTS: Fifty-one patients, including 37 esophageal cancer
      patients were enrolled, of whom 41 (80%) completed the treatment protocol as
      planned. The complete response rate for the overall period was 43% (95%
      confidence interval: 29-58); the primary endpoint was not met. Vomiting was
      frequently observed, with the overall rate of 51%. Most events occurred during 24
      72 h after chemotherapy. Somnolence was observed in 73% of the patients, but it
      was well tolerated in most cases. CONCLUSIONS: Olanzapine combined with
      palonosetron and dexamethasone did not prevent chemotherapy-induced nausea and
      vomiting induced by cisplatin as expected. The safety of this antiemetic therapy
      was confirmed.

PMID- 27030366
TI  - Diverse tetrahedral tetrazolate frameworks with N-rich surface.
AB  - Three tetrahedral tetrazolate frameworks (TTFs) with SOD, and topologies (TTF-4, 
      5 and -6) are obtained by using the anion and solvent as structure-directing
      agents. The resulting SOD-type TTF-4 shows high chemical stability as well as
      high CO2 uptake capacity. 

PMID- 27030367
TI  - A cobalt oxyhydroxide nanoflake-based nanoprobe for the sensitive fluorescence
      detection of T4 polynucleotide kinase activity and inhibition.
AB  - Phosphorylation of nucleic acids with 5'-OH termini catalyzed by polynucleotide
      kinase (PNK) is an inevitable process and has been implicated in many important
      cellular events. Here, we found for the first time that there was a significant
      difference in the adsorbent ability of cobalt oxyhydroxide (CoOOH) nanoflakes
      between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which
      resulted in the fluorescent dye-labeled dsDNA still retaining strong fluorescence
      emission, while the fluorescence signal of ssDNA was significantly quenched by
      CoOOH nanoflakes. Based on this discovery, we developed a CoOOH nanoflake-based
      nanoprobe for the fluorescence sensing of T4 PNK activity and its inhibition by
      combining it with lambda exonuclease cleavage reaction. In the presence of T4
      PNK, dye-labeled dsDNA was phosphorylated and then cleaved by lambda exonuclease
      to generate ssDNA, which could adsorb on the CoOOH nanoflakes and whose
      fluorescence was quenched by CoOOH nanoflakes. Due to the high quenching property
      of CoOOH nanoflakes as an efficient energy acceptor, a sensitive and selective
      sensing approach with satisfactory performance for T4 PNK sensing in a complex
      biological matrix has been successfully constructed and applied to the screening
      of inhibitors. The developed approach may potentially provide a new platform for
      further research, clinical diagnosis, and drug discovery of nucleotide kinase
      related diseases. 

PMID- 27030370
TI  - Identification, Collection, and Preservation of Veterinary Forensic Evidence: On
      Scene and During the Postmortem Examination.
AB  - Although it is the obligation of the veterinary forensic pathologist to be
      competent in identifying, collecting, and preserving evidence from the body, it
      is also necessary for them to understand the relevance of conditions on the crime
      scene. The body is just one piece of the puzzle that needs to be considered when
      determining the cause of death. The information required for a complete
      postmortem analysis should also include details of the animal's environment and
      items of evidence present on the crime scene. These factors will assist the
      veterinary forensic pathologist in the interpretation of necropsy findings.
      Therefore, the veterinary forensic pathologist needs to have a basic
      understanding of how the crime scene is processed, as well as the role of the
      forensic veterinarian on scene. In addition, the veterinary forensic pathologist
      must remain unbiased, necessitating an understanding of evidence maintenance and
      authentication.

PMID- 27030369
TI  - Inflammatory Potential of Diet and Risk of Ulcerative Colitis in a Case-Control
      Study from Iran.
AB  - Diet and inflammation have been suggested to be important risk factors for
      ulcerative colitis (UC). In this case-control study conducted in Iran, we
      examined the ability of the dietary inflammatory index (DII) to predict UC. This
      study included 62 UC cases and 124 controls hospitalized for acute non-neoplastic
      diseases. The DII was computed based on dietary intake assessed by a previously
      validated food frequency questionnaire. Multivariable logistic regression models
      were used to estimate odds ratios (ORs) and the DII was analyzed as both
      continuous and as tertiles. Energy was adjusted using the residual method.
      Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a
      higher risk of UC, with the DII being used as both a continuous variable
      (OR(continuous) 1.55, 95% confidence interval (CI) 1.04-2.32; one unit increase
      corresponding to ~8% of its range in the current study) and as tertiles
      (OR(tertile3vstertile1) 2.58, 95% CI 1.03-6.48, P(trend)| = |0.04). These results
      indicate that a pro-inflammatory diet is associated with increased risk of UC.

PMID- 27030368
TI  - Kinetic, Mutational, and Structural Studies of the Venezuelan Equine Encephalitis
      Virus Nonstructural Protein 2 Cysteine Protease.
AB  - The Venezuelan equine encephalitis virus (VEEV) nonstructural protein 2 (nsP2)
      cysteine protease (EC 3.4.22.-) is essential for viral replication and is
      involved in the cytopathic effects (CPE) of the virus. The VEEV nsP2 protease is
      a member of MEROPS Clan CN and characteristically contains a papain-like protease
      linked to an S-adenosyl-l-methionine-dependent RNA methyltransferase (SAM MTase)
      domain. The protease contains an alternative active site motif, (475)NVCWAK(480),
      which differs from papain's (CGS(25)CWAFS), and the enzyme lacks a transition
      state-stabilizing residue homologous to Gln-19 in papain. To understand the roles
      of conserved residues in catalysis, we determined the structure of the free
      enzyme and the first structure of an inhibitor-bound alphaviral protease. The
      peptide-like E64d inhibitor was found to bind beneath a beta-hairpin at the
      interface of the SAM MTase and protease domains. His-546 adopted a conformation
      that differed from that found in the free enzyme; one or both of the conformers
      may assist in leaving group departure of either the amine or Cys thiolate during
      the catalytic cycle. Interestingly, E64c (200 MUM), the carboxylic acid form of
      the E64d ester, did not inhibit the nsP2 protease. To identify key residues
      involved in substrate binding, a number of mutants were analyzed. Mutation of the
      motif residue, N475A, led to a 24-fold reduction in kcat/Km, and the conformation
      of this residue did not change after inhibition. N475 forms a hydrogen bond with
      R662 in the SAM MTase domain, and the R662A and R662K mutations both led to 16
      fold decreases in kcat/Km. N475 forms the base of the P1 binding site and likely
      orients the substrate for nucleophilic attack or plays a role in product release.
      An Asn homologous to N475 is similarly found in coronaviral papain-like proteases
      (PLpro) of the Severe Acute Respiratory Syndrome (SARS) virus and Middle East
      Respiratory Syndrome (MERS) virus. Mutation of another motif residue, K480A, led
      to a 9-fold decrease in kcat and kcat/Km. K480 likely enhances the
      nucleophilicity of the Cys. Consistent with our substrate-bound models, the SAM
      MTase domain K706A mutation increased Km 4.5-fold to 500 MUM. Within the beta
      hairpin, the N545A mutation slightly but not significantly increased kcat and Km.
      The structures and identified active site residues may facilitate the discovery
      of protease inhibitors with antiviral activity.

PMID- 27030371
TI  - Integrating the Forensic Sciences in Wildlife Case Investigations: A Case Report
      of Pentobarbital and Phenytoin Toxicosis in a Bald Eagle (Haliaeetus
      leucocephalus).
AB  - The application of medical knowledge to the purpose of law is the foundation of
      forensic pathology. A forensic postmortem examination often involves the
      expertise of multiple scientific disciplines to reconstruct the full story
      surrounding the death of an animal. Wildlife poses additional challenges in
      forensic investigations due to little or no associated history, and the
      disruptive effects of decomposition. To illustrate the multidisciplinary nature
      of wildlife forensic medicine, the authors outline a case of secondary
      pentobarbital/phenytoin toxicosis in a bald eagle (Haliaeetus leucocephalus). The
      eagle was the single fatality in a group of 8 birds that fed on euthanized
      domestic cat remains that had been improperly disposed of in a landfill.
      Cooperation between responding law enforcement officers, pathologists, and other
      forensic scientists led to the successful diagnosis and resolution of the case.

PMID- 27030372
TI  - Quantum stochastic walks on networks for decision-making.
AB  - Recent experiments report violations of the classical law of total probability
      and incompatibility of certain mental representations when humans process and
      react to information. Evidence shows promise of a more general quantum theory
      providing a better explanation of the dynamics and structure of real decision
      making processes than classical probability theory. Inspired by this, we show how
      the behavioral choice-probabilities can arise as the unique stationary
      distribution of quantum stochastic walkers on the classical network defined from
      Luce's response probabilities. This work is relevant because (i) we provide a
      very general framework integrating the positive characteristics of both quantum
      and classical approaches previously in confrontation, and (ii) we define a
      cognitive network which can be used to bring other connectivist approaches to
      decision-making into the quantum stochastic realm. We model the decision-maker as
      an open system in contact with her surrounding environment, and the time-length
      of the decision-making process reveals to be also a measure of the process'
      degree of interplay between the unitary and irreversible dynamics. Implementing
      quantum coherence on classical networks may be a door to better integrate human
      like reasoning biases in stochastic models for decision-making. 

PMID- 27030373
TI  - A mild preparation of alkynes from alkenyl triflates.
AB  - We report herein a protocol for preparing alkynes from alkenyl triflates.
      Stoichiometric LiCl promotes this transformation in DMF at ambient temperature. A
      range of terminal and internal alkynes were obtained smoothly. A one-pot
      procedure of alkyne formation/Cu-mediated Huisgen cycloaddition was developed,
      which may find use in synthesizing natural product-based probes. 

PMID- 27030374
TI  - The surface structure matters: thermal stability of phthalic acid anchored to
      atomically-defined cobalt oxide films.
AB  - We have investigated the influence of the structure of oxide surfaces on the
      thermal stability of anchored phthalic acid (PA) thin films. Specifically, we
      have performed temperature programmed infrared reflection absorption spectroscopy
      (TP-IRAS) of PA films deposited by physical vapor deposition (PVD) in ultra-high
      vacuum (UVH) onto three well-ordered surfaces: Co3O4(111), CoO(111) and CoO(100),
      all grown on Ir(100). Restructuring and desorption of PA were monitored in situ
      by TP-IRAS. Upon annealing of PA multilayers, co-adsorbed phthalic anhydride
      (PAA) desorbs at 200 K and a structural transition to a flat-lying adsorption
      geometry occurs at 250 K, before the PA multilayer desorbs at 300 K. At
      temperatures up to 400 K co-adsorbed mono-carboxylates partially desorb and
      partially convert to bis-carboxylates. Pronounced structure dependencies are
      observed regarding the thermal stability of the anchored bis-carboxylate
      monolayers. From Co3O4(111) the anchored PA desorbs over a wide range of
      temperatures centered at around 540 K. Weaker binding is observed for CoO(111)
      with desorption temperatures centered around 490 K. The strongest binding occurs
      on CoO(100), where the anchored PA films are found to be perfectly stable up to
      510 K, before desorption starts and centers at around 580 K. The differences in
      binding strength are rationalized based on the density and the accessibility of
      the surface Co(2+) ions. The findings show that the atomic structure of the oxide
      surface plays an important role in the stability of organic hybrid interfaces.

PMID- 27030375
TI  - Passivity analysis of uncertain stochastic neural networks with time-varying
      delays and Markovian jumping parameters.
AB  - This paper investigates the problem of robust passivity of uncertain stochastic
      neural networks with time-varying delays and Markovian jumping parameters. To
      reflect most of the dynamical behaviors of the system, both parameter
      uncertainties and stochastic disturbances are considered; stochastic disturbances
      are given in the form of a Brownian motion. By utilizing the Lyapunov functional
      method, the Ito differential rule, and matrix analysis techniques, we establish a
      sufficient criterion such that, for all admissible parameter uncertainties and
      stochastic disturbances, the stochastic neural network is robustly passive in the
      sense of expectation. A delay-dependent stability condition is formulated, in
      which the restriction of the derivative of the time-varying delay should be less
      than 1 is removed. The derived criteria are expressed in terms of linear matrix
      inequalities that can be easily checked by using the standard numerical software.
      Illustrative examples are presented to demonstrate the effectiveness and
      usefulness of the proposed results. 

PMID- 27030376
TI  - College Students' Physical Activity and Health-Related Quality of Life: An
      Achievement Goal Perspective.
AB  - PURPOSE: The 2 * 2 achievement goal model, including the mastery-approach,
      mastery-avoidance, performance-approach, and performance-avoidance goal
      orientations, has recently been used to explain motivational outcomes in physical
      activity. This study attempted to examine the relationships among 2 * 2
      achievement goal orientations, physical activity, and health-related quality of
      life (HRQOL) in college students. METHOD: Participants were 325 students (130 men
      and 195 women; Mage = 21.4 years) enrolled in physical activity classes at a
      Southern university. They completed surveys validated in previous research
      assessing achievement goal orientations, physical activity, and HRQOL. RESULTS:
      Path analyses revealed a good fit between the model and data (root mean square
      error of approximation = .06; Comparative Fit Index = .99; Bentler-Bonett
      Nonnormed Fit Index = .98; Incremental Fit Index = .99), but the model explained
      small variances in the current study. Mastery-approach and performance-approach
      goal orientations only had low or no relationships with physical activity.
      Mastery-approach goal orientation and physical activity also had low positive
      relationships with HRQOL, but mastery-avoidance and performance-avoidance goal
      orientations had low negative relationships with HRQOL. The hypothesized
      mediational role of physical activity in the relationship between mastery
      approach and performance-approach goal orientations and HRQOL was not supported
      in this study. CONCLUSIONS: Although the data fit the proposed model well, only
      small variance was explained by the model. The relationship between physical
      activity and HRQOL of the college students and other related correlates should be
      further studied.

PMID- 27030377
TI  - Polysaccharides based nanomaterials for targeted anti-cancer drug delivery.
AB  - Polysaccharides, an important class of biological polymers, are effectively
      bioactive, nontoxic, hydrophilic, biodegradable and offer a wide diversity in
      structure and properties. These can be easily modified chemically and
      biochemically to enhance the bioadhesion with biological tissues, better
      stability and can improve bioavailability of drugs. Most of the chemotherapeutic
      drugs have a narrow therapeutic index, slow drug delivery systems and poor water
      solubility that usually proves toxic to human bodies. The inherent
      biocompatibility of these biopolymers have shown enhancement of solubility of
      some chemotherapeutic drugs which also leads to the preparation of nanomaterials
      for the delivery of antibiotics, anticancer, proteins, peptides and nucleic acids
      using several routes of administration. Recently, synthesis and research on
      polysaccharides based nanomaterials have gained enormous attention as one of the
      most applicable resources in nanomedicine area. This review article will provide
      a specific emphasis on polysaccharides as natural biomaterials for targeted
      anticancer drug delivery system.

PMID- 27030378
TI  - Enhanced c-Fos expression in the central amygdala correlates with increased
      thigmotaxis in rats with peripheral nerve injury.
AB  - BACKGROUND: Pain is associated with affective, cognitive and sensory dysfunction.
      Animal models can be used to observe ethologically relevant behaviours such as
      thigmotaxis, giving insight into how ongoing sensory abnormalities influence
      natural rodent behaviours. The amygdala is a complex group of nuclei implicated
      in the integration and generation of emotional behavioural responses, including
      those associated with pain, and a region known as the central amygdala is
      particularly associated with generation of behavioural responses, due to its
      links to the descending pain modulation pathways; as such, study of amygdalar c
      Fos immunoreactivity can help identify the neuronal circuits involved. METHOD:
      This study investigated changes in both nociceptive evoked responses and open
      field behaviour following spinal nerve transection (SNT) in male Wistar rats, and
      attempted to correlate these with changes in central amygdala c-Fos
      immunoreactivity. RESULTS: Fourteen days after SNT, mechanical hypersensitivity
      was present in the hind paw ipsilateral to site of injury. Thigmotactic behaviour
      was significantly increased in both SNT and sham surgery animals, with c-Fos
      immunoreactivity in the central amygdala significantly greater in SNT animals
      compared to both sham and naive groups. Activation was greatest in the capsular
      and lateral subnuclei of the central amygdala, and in the caudal-most regions.
      There was a strong correlation between thigmotactic behaviour and central
      amygdala activation following SNT surgery not seen in sham animals suggesting a
      role for the amygdala in behavioural responses to peripheral nerve injury.
      CONCLUSIONS: This study provides evidence to support the role of the amygdala in
      thigmotactic open field behaviour following SNT. WHAT DOES THIS STUDY ADD?:
      Thigmotaxis and amygdala activation are positively correlated in rats following
      spinal nerve transection. Behavioural changes seen in sham animals did not
      correlate with amygdala activation, suggesting amygdala activation is related to
      nociceptive input. Evoked measures, such as hindpaw withdrawal, are not
      correlated with either thigmotaxis or amygdala activation, emphasizing the
      importance of complex behaviours when studying pain.

PMID- 27030379
TI  - Field-driven domain wall motion under a bias current in the creep and flow
      regimes in Pt/[CoSiB/Pt]N nanowires.
AB  - The dynamics of magnetic domain wall (DW) in perpendicular magnetic anisotropy
      Pt/[CoSiB/Pt]N nanowires was studied by measuring the DW velocity under a
      magnetic field (H) and an electric current (J) in two extreme regimes of DW creep
      and flow. Two important findings are addressed. One is that the field-driven DW
      velocity increases with increasing N in the flow regime, whereas the trend is
      inverted in the creep regime. The other is that the sign of spin current-induced
      effective field is gradually reversed with increasing N in both DW creep and flow
      regimes. To reveal the underlying mechanism of new findings, we performed further
      experiment and micromagnetic simulation, from which we found that the observed
      phenomena can be explained by the combined effect of the DW anisotropy,
      Dzyaloshinskii-Moriya interaction, spin-Hall effect, and spin-transfer torques.
      Our results shed light on the mechanism of DW dynamics in novel amorphous PMA
      nanowires, so that this work may open a path to utilize the amorphous PMA in
      emerging DW-based spintronic devices. 

PMID- 27030380
TI  - An overview of multidimensional liquid phase separations in food analysis.
AB  - Food safety is a priority public health concern that demands analytical methods
      capable to detect low concentration level of contaminants (e.g. pesticides and
      antibiotics) in different food matrices. Due to the high complexity of these
      matrices, a sample preparation step is in most cases mandatory to achieve
      satisfactory results being usually tedious, lengthy, and prone to the
      introduction of errors. For this reason, many research groups have focused
      efforts on the development of online systems capable to do the cleanup,
      concentration, and separation steps at once through multidimensional separation
      techniques (MDS). Among several possible setups, the most popular are the
      multidimensional chromatographic techniques (MDC) that consist in combining more
      than one mobile and/or stationary phase to provide a satisfactory separation. In
      the present review, we selected a variety of multidimensional separation systems
      used for food contaminant analysis in order to discuss the instrumentation
      aspects, the concept of orthogonality, column approaches used in these systems,
      and new materials that can be used in these columns. Selected classes of
      contaminants present in food matrices are introduced and discussed as example of
      the potential applications of multidimensional liquid phase separation techniques
      in food safety.

PMID- 27030381
TI  - Limbic Encephalitis Associated With GAD65 Antibodies: Brief Review of the
      Relevant literature.
AB  - Recently, many cases of autoimmune limbic encephalitis with positive GAD65
      (glutamic acid decarboxylase) antibodies have been described in the scientific
      literature. However, it remains an understudied topic of great relevance to
      practicing neurologists. Thus, we report here a review of published cases, in
      English, of autoimmune limbic encephalitis with this type of antibodies, focusing
      on presenting symptoms and signs, associated conditions, and findings upon
      investigation. We also report treatment responses. We aim to offer a better
      description of the clinical spectrum of autoimmune limbic encephalitis associated
      with GAD65 antibodies as well as to expose its paraclinical features and outcome.

PMID- 27030382
TI  - Redox proteins of hydroxylating bacterial dioxygenases establish a regulatory
      cascade that prevents gratuitous induction of tetralin biodegradation genes.
AB  - Bacterial dioxygenase systems are multicomponent enzymes that catalyze the
      initial degradation of many environmentally hazardous compounds. In Sphingopyxis
      granuli strain TFA tetralin dioxygenase hydroxylates tetralin, an organic
      contaminant. It consists of a ferredoxin reductase (ThnA4), a ferredoxin (ThnA3)
      and a oxygenase (ThnA1/ThnA2), forming a NAD(P)H-ThnA4-ThnA3-ThnA1/ThnA2 electron
      transport chain. ThnA3 has also a regulatory function since it prevents
      expression of tetralin degradation genes (thn) in the presence of non
      metabolizable substrates of the catabolic pathway. This role is of physiological
      relevance since avoids gratuitous and wasteful production of catabolic enzymes.
      Our hypothesis for thn regulation implies that ThnA3 exerts its action by
      diverting electrons towards the regulator ThnY, an iron-sulfur flavoprotein that
      together with the transcriptional activator ThnR is necessary for thn gene
      expression. Here we analyze electron transfer among ThnA4, ThnA3 and ThnY by
      using stopped-flow spectrophotometry and determination of midpoint reduction
      potentials. Our results indicate that when accumulated in its reduced form ThnA3
      is able to fully reduce ThnY. In addition, we have reproduced in vitro the
      regulatory circuit in the proposed physiological direction, NAD(P)H-ThnA4-ThnA3
      ThnY. ThnA3 represents an unprecedented way of communication between a catabolic
      pathway and its regulatory system to prevent gratuitous induction. 

PMID- 27030383
TI  - Analysis of the association between host genetics, smoking, and sputum microbiota
      in healthy humans.
AB  - Recent studies showing clear differences in the airway microbiota between healthy
      and diseased individuals shed light on the importance of the airway microbiota in
      health. Here, we report the associations of host genetics and lifestyles such as
      smoking, alcohol consumption, and physical activity with the composition of the
      sputum microbiota using 16S rRNA gene sequence data generated from 257 sputum
      samples of Korean twin-family cohort. By estimating the heritability of each
      microbial taxon, we found that several taxa, including Providencia and
      Bacteroides, were significantly influenced by host genetic factors. Smoking had
      the strongest effect on the overall microbial community structure among the
      tested lifestyle factors. The abundances of Veillonella and Megasphaera were
      higher in current-smokers, and increased with the pack-year value and the
      Fagerstrom Test of Nicotine Dependence (FTND) score. In contrast, Haemophilus
      decreased with the pack-year of smoking and the FTND score. Co-occurrence network
      analysis showed that the taxa were clustered according to the direction of
      associations with smoking, and that the taxa influenced by host genetics were
      found together. These results demonstrate that the relationships among sputum
      microbial taxa are closely associated with not only smoking but also host
      genetics. 

PMID- 27030384
TI  - miR-21 contributes to renal protection by targeting prolyl hydroxylase domain
      protein 2 in delayed ischaemic preconditioning.
AB  - AIM: Upregulation of miR-21 in renal ischaemic preconditioning (IPC) was
      associated with increased hypoxia inducible factor (HIF)-1alpha expression.
      Hypoxic induction of HIF-1alpha is mediated by inhibition of prolyl hydroxylase
      domain protein 2 (PHD2) .We hypothesized that miR-21 regulated HIF-1alpha by
      targeting PHD2 in the renal IPC. METHODS: Luciferase reporter assay examined if
      miR-21 target the 3'-untranslated region of PHD2. In vitro, human proximal
      tubular cell line (HK-2) was incubated in hypoxia or hypoxia/ reoxygenation
      condition. Kidneys of Mice were respectively subjected to ischaemia/reperfusion
      injury (IRI) and IPC. Locked nucleic acid (LNA) modified anti-miR-21 was used to
      knockdown miR-21. Serum creatinine and histological changes estimated the renal
      injury. Levels of HIF-1alpha, PHD2, VEGF and miR-21 were examined by western blot
      or real-time PCR. RESULT: miR-21 targeting of PHD2 was confirmed by 3'
      untranslated region reporter assay. miR-21 was significantly upregulated by
      hypoxia/reoxygenation in HK-2 cell, while PHD2 protein level decreased
      significantly. LNA anti-miR-21 significantly repressed miR-21 levels and
      increased the abundance of PHD2. In vivo, IPC upregulated miR-21 expression 24 h
      after the second ischaemia, while PHD2 expression decreased significantly with
      upregulation of HIF-1alpha protein and VEGF mRNA. MiR-21 induced by delayed IPC
      was effectively inhibited by the LNA anti-miR-21. With downregulation of miR-21,
      the protection of delayed IPC was attenuated and PHD2 protein was increased.
      Furthermore, upregulation of HIF-1alpha and VEGF were abolished after the LNA
      anti-miR-21 treatment. CONCLUSION: miR-21 could protect kidney against IRI via
      HIF-1alpha by inhibiting its target PHD2.The study suggested a new relationship
      between miR-21 and HIF-1alpha.

PMID- 27030386
TI  - Physical exercise training interventions for children and young adults during and
      after treatment for childhood cancer.
AB  - BACKGROUND: A decreased physical fitness has been reported in patients and
      survivors of childhood cancer. This is influenced by the negative effects of the
      disease and the treatment of childhood cancer. Exercise training for adult cancer
      patients has frequently been reported to improve physical fitness. In recent
      years, literature on this subject has also become available for children and
      young adults with cancer, both during and after treatment. This is an update of
      the original review that was performed in 2011. OBJECTIVES: To evaluate the
      effect of a physical exercise training intervention on the physical fitness (i.e.
      aerobic capacity, muscle strength, or functional performance) of children with
      cancer within the first five years from their diagnosis (performed either during
      or after cancer treatment), compared to a control group of children with cancer
      who did not receive an exercise intervention.To determine whether physical
      exercise within the first five years of diagnosis has an effect on fatigue,
      anxiety, depression, self efficacy, and HRQoL and to determine whether there are
      any adverse effects of the intervention. SEARCH METHODS: We searched the
      electronic databases of Cochrane Register of Controlled Trials (CENTRAL),
      MEDLINE, EMBASE, CINAHL, and PEDro; ongoing trial registries and conference
      proceedings on 6 September 2011 and 11 November 2014. In addition, we performed a
      handsearch of reference lists. SELECTION CRITERIA: The review included randomized
      controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the
      effects of physical exercise training with no training, in people who were within
      the first five years of their diagnosis of childhood cancer. DATA COLLECTION AND
      ANALYSIS: Two review authors independently identified studies meeting the
      inclusion criteria, performed the data extraction, and assessed the risk of bias
      using standardized forms. Study quality was rated by the Grading of
      Recommendation Assessment, Development and Evaluation (GRADE) criteria. MAIN
      RESULTS: Apart from the five studies in the original review, this update included
      one additional RCT. In total, the analysis included 171 participants, all during
      treatment for childhood acute lymphoblastic leukaemia (ALL).The duration of the
      training sessions ranged from 15 to 60 minutes per session. Both the type of
      intervention and intervention period varied in all the included studies. However,
      the control group always received usual care.All studies had methodological
      limitations, such as small numbers of participants, unclear randomization
      methods, and single-blind study designs in case of one RCT and all results were
      of moderate to very low quality (GRADE).Cardiorespiratory fitness was evaluated
      by the 9-minute run-walk test, timed up-and-down stairs test, the timed up-and-go
      time test, and the 20-m shuttle run test. Data of the 9-minute run-walk test and
      the timed up-and-down stairs test could be pooled. The combined 9-minute run-walk
      test results showed significant differences between the intervention and the
      control groups, in favour of the intervention group (standardized mean difference
      (SMD) 0.69; 95% confidence interval (CI) 0.02 to 1.35). Pooled data from the
      timed up-and-down stairs test showed no significant differences in
      cardiorespiratory fitness (SMD -0.54; 95% CI -1.77 to 0.70). However, there was
      considerable heterogeneity (I(2) = 84%) between the two studies on this outcome.
      The other two single-study outcomes, 20-m shuttle run test and the timed up-and
      go test, also showed positive results for cardiorespiratory fitness in favour of
      the intervention group.Only one study assessed the effect of exercise on bone
      mineral density (total body), showing a statistically significant positive
      intervention effect (SMD 1.07; 95% CI 0.48 to 1.66). The pooled data on body mass
      index showed no statistically significant end-score difference between the
      intervention and control group (SMD 0.59; 95% CI -0.23 to 1.41).Three studies
      assessed flexibility. Two studies assessed ankle dorsiflexion. One study assessed
      active ankle dorsiflexion, while the other assessed passive ankle dorsiflexion.
      There were no statistically significant differences between the intervention and
      control group with the active ankle dorsiflexion test; however, in favour of the
      intervention group, they were found for passive ankle dorsiflexion (SMD 0.69; 95%
      CI 0.12 to 1.25). The third study assessed body flexibility using the sit-and
      reach distance test, but identified no statistically significant difference
      between the intervention and control group.Three studies assessed muscle strength
      (knee, ankle, back and leg, and inspiratory muscle strength). Only the back and
      leg strength combination score showed statistically significant differences on
      the muscle strength end-score between the intervention and control group (SMD
      1.41; 95% CI 0.71 to 2.11).Apart from one sub-scale of the cancer scale (Worries;
      P value = 0.03), none of the health-related quality of life scales showed a
      significant difference between both study groups on the end-score. For the other
      outcomes of fatigue, level of daily activity, and adverse events (all assessed in
      one study), there were no statistically significant differences between the
      intervention and control group.None of the included studies evaluated activity
      energy expenditure, time spent on exercise, anxiety and depression, or self
      efficacy as an outcome. AUTHORS' CONCLUSIONS: The effects of physical exercise
      training interventions for childhood cancer participants are not yet convincing.
      Possible reasons are the small numbers of participants and insufficient study
      designs, but it can also be that this type of intervention is not as effective as
      in adult cancer patients. However, the first results show some positive effects
      on physical fitness in the intervention group compared to the control group.
      There were positive intervention effects for body composition, flexibility,
      cardiorespiratory fitness, muscle strength, and health-related quality of life
      (cancer-related items). These were measured by some assessment methods, but not
      all. However, the quality of the evidence was low and these positive effects were
      not found for the other assessed outcomes, such as fatigue, level of daily
      activity, and adverse events. There is a need for more studies with comparable
      aims and interventions, using a higher number of participants that also include
      diagnoses other than ALL.

PMID- 27030385
TI  - Anti-Mullerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope
      activity before puberty.
AB  - Anti-Mullerian hormone (AMH) contributes to male sexual differentiation and acts
      on gonads of both sexes. Identification of AMH receptivity in both pituitary and
      brain has led to the intriguing idea that AMH participates to the hypothalamic
      pituitary control of reproduction, however in vivo experimental evidence is still
      lacking. We show that AMH stimulates secretion and pituitary gene expression of
      the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being
      restricted to females and occurring before puberty. Accordingly, we report higher
      levels of pituitary AMH receptor transcripts in immature females. We show that
      AMH is functionally coupled to the Smad pathway in LbetaT2 gonadotrope cells and
      dose-dependently increases Fshb transcript levels. Furthermore, AMH was shown to
      establish complex interrelations with canonical FSH regulators as it cooperates
      with activin to induce Fshb expression whereas it reduces BMP2 action. We report
      that GnRH interferes with AMH by decreasing AMH receptivity in vivo in females.
      Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a
      factor contributing to the differential regulation of gonadotropins. Overall, our
      study uncovers a new role for AMH in regulating gonadotrope function and suggests
      that AMH participates in the postnatal elevation of FSH secretion in females. 

PMID- 27030387
TI  - Preparing Student Nurses as Parent-based Adolescent Sexual Health Educators:
      Results of a Pilot Study.
AB  - OBJECTIVES: While health promotion and patient education are central to the scope
      of practice of professional nurses, they often feel ill-equipped to assume the
      role of sexual health educator and lack adequate knowledge and skills to
      effectively engage parents in adolescent sexual and reproductive health efforts.
      DESIGN AND SAMPLE: Employing a mixed-methods study consisting of both pre- and
      post-test survey and exit interviews, a pilot study was conducted to assess the
      impact of implementing a parent-based adolescent sexual health intervention on
      baccalaureate nursing student outcomes (N = 31). RESULTS: We found statistically
      significant improvements in student outcome expectancies of parenting strategies,
      barriers to sexual health communication, self-efficacy, and sexual health
      counseling experience. Using thematic content analysis of exit interview content,
      emerging themes were (1) need for increased sexual and reproductive health (SRH)
      preparation, (2) wanting greater experience and opportunity for involvement in
      nursing research, and (3) educational gaps in family-focused community public
      health. CONCLUSIONS: Incorporating adolescent sexual health education into public
      health nursing clinical training can prepare nurses as parent-based adolescent
      sexual health educators, a core competency for nurses working with families in
      communities and across all health care delivery settings.

PMID- 27030388
TI  - Two cases of cyclic neutropenia with acquired CSF3R mutations, with 1 developing
      AML.

PMID- 27030389
TI  - Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas.
AB  - Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive
      types of B-cell lymphoma. Deregulation of proto-oncogene expression after a
      translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one
      of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have
      identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in
      DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD
      L1/PD-L2 Fluorescence in situ hybridization was furthermore used to rapidly
      screen an expanded DLBCL cohort. Collectively, a subset of samples was found to
      be affected by gains (12%), amplifications (3%), and translocations (4%) of the
      PD-L1/PD-L2 locus. RNA sequencing data coupled with immunohistochemistry revealed
      that these cytogenetic alterations correlated with increased expression of PD-L1
      but not of PD-L2 Moreover, cytogenetic alterations affecting the PD-L1/PD-L2
      locus were more frequently observed in the non-germinal center B cell-like (non
      GCB) subtype of DLBCL. These findings demonstrate the genetic basis of PD-L1
      overexpression in DLBCL and suggest that treatments targeting the PD-1-PD-L1/PD
      L2 axis might benefit DLBCL patients, especially those belonging to the more
      aggressive non-GCB subtype.

PMID- 27030391
TI  - YSZ thin films with minimized grain boundary resistivity.
AB  - In recent years, interface engineering of solid electrolytes has been explored to
      increase their ionic conductivity and improve the performance of solid oxide fuel
      cells and other electrochemical power sources. It has been observed that the
      ionic conductivity of epitaxially grown thin films of some electrolytes is
      dramatically enhanced, which is often attributed to effects (e.g. strain-induced
      mobility changes) at the heterophase boundary with the substrate. Still largely
      unexplored is the possibility of manipulation of grain boundary resistivity in
      polycrystalline solid electrolyte films, clearly a limiting factor in their ionic
      conductivity. Here we report that the ionic conductivity of yttria stabilized
      zirconia thin films with nano-columnar grains grown on a MgO substrate nearly
      reaches that of the corresponding single crystal when the thickness of the films
      becomes less than roughly 8 nm (smaller by a factor of three at 500  degrees C).
      Using impedance spectroscopy, the grain boundary resistivity was probed as a
      function of film thickness. The resistivity of the grain boundaries near the film
      substrate interface and film surface (within 4 nm of each) was almost entirely
      eliminated. This minimization of grain boundary resistivity is attributed to
      Mg(2+) diffusion from the MgO substrate into the YSZ grain boundaries, which is
      supported by time of flight secondary ion mass spectroscopy measurements. We
      suggest grain boundary "design" as an attractive method to obtain highly
      conductive solid electrolyte thin films.

PMID- 27030390
TI  - Alloantigen presentation and graft-versus-host disease: fuel for the fire.
AB  - Allogeneic stem cell transplantation (SCT) is a unique procedure, primarily in
      patients with hematopoietic malignancies, involving chemoradiotherapy followed by
      the introduction of donor hematopoietic and immune cells into an inflamed and
      lymphopenic environment. Interruption of the process by which recipient
      alloantigen is presented to donor T cells to generate graft-versus-host disease
      (GVHD) represents an attractive therapeutic strategy to prevent morbidity and
      mortality after SCT and has been increasingly studied in the last 15 years.
      However, the immune activation resulting in GVHD has no physiological equivalent
      in nature; alloantigen is ubiquitous, persists indefinitely, and can be presented
      by multiple cell types at numerous sites, often on incompatible major
      histocompatibility complex, and occurs in the context of intense inflammation
      early after SCT. The recognition that alloantigen presentation is also critical
      to the development of immunological tolerance via both deletional and regulatory
      mechanisms further adds to this complexity. Finally, GVHD itself appears capable
      of inhibiting the presentation of microbiological antigens by donor dendritic
      cells late after SCT that is mandatory for the establishment of effective
      pathogen-specific immunity. Here, we review our current understanding of
      alloantigen, its presentation by various antigen-presenting cells, subsequent
      recognition by donor T cells, and the potential of therapeutic strategies
      interrupting this disease-initiating process to modify transplant outcome.

PMID- 27030392
TI  - The class III anti-arrhythmic agent, amiodarone, inhibits voltage-dependent K(+)
      channels in rabbit coronary arterial smooth muscle cells.
AB  - We examined the inhibitory effect of amiodarone, a class III anti-arrhythmic
      agent, on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit
      coronary arterial smooth muscle cells, using a whole-cell patch clamp technique.
      Amiodarone inhibited Kv currents in a concentration-dependent manner, with a half
      maximal inhibitory concentration (IC50) value of 3.9 +/- 1.44 MUM and a Hill
      coefficient of 0.45 +/- 0.14. Amiodarone did not have a significant effect on the
      steady-state activation of Kv channels, but shifted the inactivation current
      toward a more negative potential. Application of consecutive pulses progressively
      augmented the amiodarone-induced Kv channel inhibition. Another class III anti
      arrhythmic agent, dofetilide, did not inhibit the Kv current or change the
      inhibitory effect of amiodarone on Kv channels. Therefore, these results strongly
      suggest that amiodarone inhibits Kv currents in a concentration- and state
      dependent manner. 

PMID- 27030394
TI  - Promotion to MEDLINE, indexing with Medical Subject Headings, and open data
      policy for the Journal of Educational Evaluation for Health Professions.

PMID- 27030393
TI  - The disintegrin, trimucrin, suppresses LPS-induced activation of phagocytes
      primarily through blockade of NF-kappaB and MAPK activation.
AB  - In addition to antiplatelet activity, disintegrin, a small-mass RGD-containing
      polypeptide, has been shown to exert anti-inflammatory effects but the mechanism
      involved remains unclear. In this study, we report that trimucrin, a disintegrin
      from the venom of Trimeresurus mucrosquamatus, inhibits lipopolysaccharide (LPS)
      induced stimulation of THP-1 and RAW 264.7 cells. We also investigate the
      underlying mechanism. Trimucrin decreased the release of proinflammatory
      cytokines including tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6),
      nitric oxide, and reactive oxygen species (ROS), and inhibited the adhesion and
      migration of LPS-activated phagocytes. Trimucrin significantly blocked the
      expression of nuclear factor kappaB (NF-kappaB)-related downstream inducible
      enzymes such as inducible nitric oxide synthase (iNOS) and COX-2. In addition,
      its anti-inflammatory effect was associated with the decreased mitogen-activated
      protein kinase (MAPK) phosphorylation. Furthermore, trimucrin concentration
      dependently inhibited LPS-induced phosphorylation of focal adhesion kinase (FAK),
      PI3K, and Akt. Trimucrin also reversed the DNA-binding activity of NF-kappaB by
      suppressing the LPS-induced nuclear translocation of p65 and the cytosolic
      IkappaB release. Flow cytometric analyses showed that trimucrin bound to cells in
      a concentration-dependent manner. The anti-alphaVbeta3 mAb also specifically
      decreased the binding of fluorescein isothiocyanate (FITC)-conjugated trimucrin.
      Binding assays demonstrated that integrin alphaVbeta3 was the binding site for
      trimucrin on THP-1 and RAW 264.7 cells. In conclusion, we showed that trimucrin
      decreases the inflammatory reaction through the attenuation of iNOS expression
      and nitric oxide (NO) production by blocking MAP kinase and the NF-kappaB
      activation in LPS-stimulated THP-1 and RAW 264.7 cells. 

PMID- 27030395
TI  - Identification of Nanopillars on the Cuticle of the Aquatic Larvae of the Drone
      Fly (Diptera: Syrphidae).
AB  - Here, we describe a nano-scale surface structure on the rat-tailed maggot, the
      aquatic larva of the Drone fly Eristalis tenax(L.). Larvae of this syrphid hover
      fly live in stagnant, anaerobic water-courses that are rich in organic matter.
      The larvae burrow into fetid slurry and feed on microorganisms which they filter
      out from the organic material. This environment is rich in bacteria, fungi and
      algae with the capacity to form biofilms that might develop on the larval surface
      and harm them. Using transmission and scanning electron microscopy we have
      identified an array of slender (typically < 100 nm in diameter) nanopillars that
      cover the surface of the larvae. The high density and dimensions of these spine
      like projections appear to make it difficult for bacteria to colonize the surface
      of the animal. This may interfere with the formation of biofilms and potentially
      act as a defence against bacterial infection.

PMID- 27030396
TI  - Declining trends in invasive orthopedic interventions for people with hemophilia
      enrolled in the Universal Data Collection program (2000-2010).
AB  - INTRODUCTION: Recurrent joint hemarthroses due to hemophilia (Factor VIII and
      Factor IX deficiency) often lead to invasive orthopedic interventions to decrease
      frequency of bleeding and/or to alleviate pain associated with end-stage
      hemophilic arthropathy. AIM: Identify trends in invasive orthopedic interventions
      among people with hemophilia who were enrolled in the Universal Data Collection
      (UDC) program during the period 2000-2010. METHODS: Data were collected from 130
      hemophilia treatment centers in the United States annually during the period 2000
      2010, in collaboration with the Centers for Disease Control and Prevention (CDC).
      The number of visits in which an invasive orthopedic intervention was reported
      was expressed as a proportion of the total visits in each year of the program.
      Invasive orthopedic interventions consisted of arthroplasty, arthrodesis, and
      synovectomy. Joints included in this study were the shoulder, elbow, hip, knee,
      and ankle. RESULTS: A 5.6% decrease in all invasive orthopedic interventions in
      all joints of people with hemophilia enrolled in the UDC program over the 11-year
      study period was observed. CONCLUSIONS: These data reflect a declining trend in
      invasive orthopedic interventions in people with hemophilia. Further research is
      needed to understand the characteristics that may influence invasive orthopedic
      interventions.

PMID- 27030398
TI  - The Drug Excipient Cyclodextrin Interacts With d-Luciferin and Interferes With
      Bioluminescence Imaging.
AB  - Cyclodextrins are well-characterized, barrel-shaped molecules that can solubilize
      organic small molecules in aqueous solution via host-guest interactions. As such,
      cyclodextrins are used as excipients for experimental therapeutics in vivo. We
      observed unanticipated modifications to bioluminescence imaging (BLI) signal
      intensity when 2-hydroxy-propyl-beta-cyclodextrin (HPCD) was coinjected as an
      excipient. We hypothesized that HPCD bindsd-luciferin and interferes with the BLI
      signal. Using luciferase-expressing cell lines, we showed that HPCD lowers the
      BLI signal in a concentration-dependent manner. Flow cytometry revealed that HPCD
      resulted in reduced cellular accumulation ofd-luciferin, and mass spectrometry
      revealedd-luciferin HPCD species, confirming a direct interaction. In vivo
      imaging using a luciferase mouse model demonstrated that HPCD reduced luciferin
      mediated BLI compared to luciferin alone. The implications of using HPCD as an
      excipient in BLI studies are discussed.

PMID- 27030397
TI  - Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807.
AB  - Early clinical results of two tau tracers, [(18)F]T808 and [(18)F]T807, have
      recently been reported. In the present study, the biodistribution,
      radiometabolite quantification, and competition-binding studies were performed in
      order to acquire comparative preclinical data as well as to establish the value
      of T808 and T807 as benchmark compounds for assessment of binding affinities of
      eight new/other tau tracers. Biodistribution studies in mice showed high brain
      uptake and fast washout.In vivoradiometabolite analysis using high-performance
      liquid chromatography showed the presence of polar radiometabolites in plasma and
      brain. No specific binding of [(18)F]T808 was found in transgenic mice expressing
      mutant human P301L tau. In semiquantitative autoradiography studies on human
      Alzheimer disease slices, we observed more than 50% tau selective blocking of
      [(18)F]T808 in the presence of 1 umol/L of the novel ligands. This study provides
      a straightforward comparison of the binding affinity and selectivity for tau of
      the reported radiolabeled tracers BF-158, BF-170, THK5105, lansoprazole,
      astemizole, and novel tau positron emission tomography ligands against T807 and
      T808. Therefore, these data are helpful to identify structural requirements for
      selective interaction with tau and to compare the performance of new highly
      selective and specific radiolabeled tau tracers.

PMID- 27030399
TI  - Labeling Human Melanoma Cells With SPIO: In Vitro Observations.
AB  - OBJECTIVES: To use the superparamagnetic iron oxide (SPIO) contrast agent
      Resovist (+/-transfection agent) to label human melanoma cells and determine its
      effects on cellular viability, microstructure, iron quantity, and magnetic
      resonance imaging (MRI) detectability. MATERIALS AND METHODS: Human SK-Mel28
      melanoma cells were incubated with Resovist (+/-liposomal transfection agent
      DOSPER). The cellular iron content was measured, and labeled cells were examined
      at 1.5 T and 3.0 T. The intracellular and extracellular distributions of the
      contrast agent were assessed by light and electron microscopy. RESULTS: The
      incubation of melanoma cells with SPIO does not interfere with cell viability or
      proliferation. The iron is located both intracellularly and extracellularly as
      iron clusters associated with the exterior of the cell membrane. Despite thorough
      washing, the extracellular SPIO remained associated with the cell membrane. The
      liposomal transfection agent does not change the maximum achievable cellular iron
      content but promotes a faster iron uptake. The MRI detectability persists for at
      least 7 days. CONCLUSION: The transfection agent DOSPER facilitates the efficient
      labeling of human metastatic melanoma cells with Resovist. Our findings raise the
      possibility that other Resovist-labeled cells may collect associated
      extracellular nanoparticles. The SPIO may be available to other iron-handling
      cells and not completely compartmentalized during the labeling procedure.

PMID- 27030400
TI  - Immunotargeting of Integrin alpha6beta4 for Single-Photon Emission Computed
      Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model.
AB  - To explore suitable imaging probes for early and specific detection of pancreatic
      cancer, we demonstrated that alpha6beta4integrin is a good target and employed
      single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging
      for immunotargeting. Expression levels of alpha6beta4were examined by Western
      blotting and flow cytometry in certain human pancreatic cancer cell lines. The
      human cell line BxPC-3 was used for alpha6beta4-positive and a mouse cell line,
      A4, was used for negative counterpart. We labeled antibody against
      alpha6beta4with Indium-111 ((111)In) or indocyanine green (ICG). After injection
      of(111)In-labeled probe to tumor-bearing mice, biodistribution, SPECT,
      autoradiography (ARG), and immunohistochemical (IHC) studies were conducted.
      After administration of ICG-labeled probe, in vivo and ex vivo NIR imaging and
      fluorescence microscopy of tumors were performed. BxPC-3 tumor showed a higher
      radioligand binding in SPECT and higher fluorescence intensity as well as a delay
      in the probe washout in NIR imaging when compared to A4 tumor. The
      biodistribution profile of(111)In-labeled probe, ARG, and IHC confirmed the
      alpha6beta4specific binding of the probe. Here, we propose that alpha6beta4is a
      desirable target for the diagnosis of pancreatic cancer and that it could be
      detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG
      labeled alpha6beta4antibody.

PMID- 27030401
TI  - Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With
      99mTc-Labeled Duramycin SPECT/CT.
AB  - Our goal was to validate the feasibility of(99m)Tc-duramycin as a potential
      apoptosis probe for monitoring tumor response to paclitaxel in breast cancer
      xenografts. The binding of(99m)Tc-duramycin to phosphatidylethanolamine was
      validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231
      cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were
      randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel
      or phosphate-buffered saline.(99m)Tc-duramycin (37-55.5 MBq) was injected at 72
      hours posttreatment, and single-photon emission computed tomography/computed
      tomography was performed at 2 hours postinjection. Apoptotic cells and activated
      caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular
      ultrastructural changes were assessed by light and transmission electron
      microscopy.(99m)Tc-duramycin with radiochemical purity of >90% exhibited rapid
      blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in
      the paclitaxel-treated group (5.29 +/- 0.62) was significantly higher than that
      in the control. Tumor volume was decreased dramatically, whereas tumor uptake
      of(99m)Tc-duramycin (ex vivo) significantly increased following paclitaxel
      treatment, which was consistent with apoptotic index, histological findings, and
      ultrastructural changes. Our data demonstrated the feasibility of(99m)Tc
      duramycin for early detection of apoptosis after paclitaxel chemotherapy in
      breast carcinoma xenografts.

PMID- 27030402
TI  - The Effects of Physiological and Methodological Determinants on 18F-FDG Mouse
      Brain Imaging Exemplified in a Double Transgenic Alzheimer Model.
AB  - INTRODUCTION: In this study, the influence of physiological determinants on 18F
      fluoro-d-glucose ((18)F-FDG) brain uptake was evaluated in a mouse model of
      Alzheimer disease. MATERIALS AND METHODS: TASTPM (Tg) and age-matched C57BL/6 J
      (WT) mice were fasted for 10 hours, while another group was fasted for 20 hours
      to evaluate the effect of fasting duration. The effect of repeatedly scanning was
      evaluated by scanning Tg and WT mice at days 1, 4, and 7. Brain (18)F-FDG uptake
      was evaluated in the thalamus being the most indicative region. Finally, the
      cerebellum was tested as a reference region for the relative standard uptake
      value (rSUV). RESULTS: When correcting the brain uptake for glucose, the effect
      of different fasting durations was attenuated and the anticipated hypometabolism
      in Tg mice was demonstrated. Also, with repeated scanning, the brain uptake
      values within a group and the hypometabolism of the Tg mice only remained stable
      over time when glucose correction was applied. Finally, hypometabolism was also
      observed in the cerebellum, yielding artificially higher rSUV values for Tg mice.
      CONCLUSION: Corrections for blood glucose levels have to be applied when
      semiquantifying (18)F-FDG brain uptake in mouse models for AD. Potential
      reference regions for normalization should be thoroughly investigated to ensure
      that they are not pathologically affected also by afferent connections.

PMID- 27030403
TI  - Sun sensitivity, indoor tanning and B-cell non-Hodgkin lymphoma risk among
      Caucasian women in Los Angeles County.

PMID- 27030404
TI  - Inhibitory Effect of Sophorolipid on Candida albicans Biofilm Formation and
      Hyphal Growth.
AB  - Candida albicans causes superficial and life-threatening systemic infections.
      These are difficult to treat often due to drug resistance, particularly because
      C. albicans biofilms are inherently resistant to most antifungals. Sophorolipid
      (SL), a glycolipid biosurfactant, has been shown to have antimicrobial and
      anticancer properties. In this study, we investigated the effect of SL on C.
      albicans biofilm formation and preformed biofilms. SL was found to inhibit C.
      albicans biofilm formation as well as reduce the viability of preformed biofilms.
      Moreover, SL, when used along with amphotericin B (AmB) or fluconazole (FLZ), was
      found to act synergistically against biofilm formation and preformed biofilms.
      Effect of SL on C. albicans biofilm formation was further visualized by scanning
      electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), which
      revealed absence of hyphae, typical biofilm architecture and alteration in the
      morphology of biofilm cells. We also found that SL downregulates the expression
      of hypha specific genes HWP1, ALS1, ALS3, ECE1 and SAP4, which possibly explains
      the inhibitory effect of SL on hyphae and biofilm formation. 

PMID- 27030406
TI  - Unhealthy eating behaviors and weight gain: A prospective study in young and
      middle-age adults.
AB  - OBJECTIVE: Guidelines for obesity prevention recommend reducing certain unhealthy
      eating behaviors (UEB). However, the association between UEB and weight gain is
      uncertain. METHODS: Prospective cohort with 1,638 individuals aged 18-60 years
      was recruited in 2008-2010. UEB assessed at baseline were: not planning how much
      to eat, consuming pre-cooked/canned food, buying snacks, eating in fast-food
      restaurants, not choosing low-calorie foods, not removing visible fat from meat
      or skin from chicken, and eating while watching TV or seating on a sofa.
      Participants were followed up through 2012 to assess weight change. RESULTS:
      Compared to reporting 0-2 UEB, the multivariate odds ratios (95% confidence
      interval) for gaining >=3 kg were 0.97 (0.74-1.28) for 3-4 UEB and 1.61 (1.09
      2.39) for >=5 UEB, P-trend = 0.07. Results were similar for gaining >=5 kg. The
      three UEB with the strongest associations with weight gain were: 1) not planning
      the amount of food to eat, 2) eating at fast-food restaurants, and 3) eating
      while watching TV; compared to having none of these three behaviors, the odds
      ratio (95% confidence interval) for gaining >=3 kg was 1.54 (0.77-3.08) for 1
      UEB, 1.70 (0.85-3.37) for 2 UEB, and 2.75 (1.28-5.90) for 3 UEB, P-trend = 0.007.
      Similar results were obtained for gaining >=5 kg. CONCLUSIONS: Several UEB are
      associated with weight gain.

PMID- 27030405
TI  - KIR2DL2/2DL3-E(35) alleles are functionally stronger than -Q(35) alleles.
AB  - KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric
      motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although
      KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is
      an important factor for donor selection in allogeneic hematopoietic stem cell
      transplantation, the molecular determinant of functional diversity among various
      alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at
      position 35 (E(35)) are functionally stronger than those with glutamine at the
      same position (Q(35)). Cytotoxicity assay showed that NK cells from HLA-C1
      positive donors with KIR2DL2/L3-E(35) could kill more target cells lacking their
      ligands than NK cells with the weaker -Q(35) alleles, indicating better licensing
      of KIR2DL2/L3(+) NK cells with the stronger alleles. Molecular modeling analysis
      reveals that the glutamic acid, which is negatively charged, interacts with
      positively charged histidine located at position 55, thereby stabilizing
      KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand.
      The results of this study will be important for future studies of KIR2DL2/L3
      associated diseases as well as for donor selection in allogeneic stem cell
      transplantation. 

PMID- 27030408
TI  - Novel or reproducible: That is the question.

PMID- 27030409
TI  - Novel GM1 ganglioside-like peptide mimics prevent the association of cholera
      toxin to human intestinal epithelial in vitro.

PMID- 27030410
TI  - Climate change surpasses land-use change in the contracting range boundary of a
      winter-adapted mammal.
AB  - The effects of climate change on biodiversity have emerged as a dominant theme in
      conservation biology, possibly eclipsing concern over habitat loss in recent
      years. The extent to which this shifting focus has tracked the most eminent
      threats to biodiversity is not well documented. We investigated the mechanisms
      driving shifts in the southern range boundary of a forest and snow cover
      specialist, the snowshoe hare, to explore how its range boundary has responded to
      shifting rates of climate and land cover change over time. We found that although
      both forest and snow cover contributed to the historical range boundary, the
      current duration of snow cover best explains the most recent northward shift,
      while forest cover has declined in relative importance. In this respect, the
      southern range boundary of snowshoe hares has mirrored the focus of conservation
      research; first habitat loss and fragmentation was the stronger environmental
      constraint, but climate change has now become the main threat. Projections of
      future range shifts show that climate change, and associated snow cover loss,
      will continue to be the major driver of this species' range loss into the future.

PMID- 27030411
TI  - Predator encounters have spatially extensive impacts on parental behaviour in a
      breeding bird community.
AB  - Predation risk has negative indirect effects on prey fitness, partly mediated
      through changes in behaviour. Evidence that individuals gather social information
      from other members of the population suggests that events in a community may
      impact the behaviour of distant individuals. However, spatially wide-ranging
      impacts on individual behaviour caused by a predator encounter elsewhere in a
      community have not been documented before. We investigated the effect of a
      predator encounter (hawk model presented at a focal nest) on the parental
      behaviour of pied flycatchers (Ficedula hypoleuca), both at the focal nest and at
      nearby nests different distances from the predator encounter. We show that nest
      visitation of both focal pairs and nearby pairs were affected, up to 3 h and 1 h,
      respectively. Parents also appeared to compensate initial disrupted feeding by
      later increasing nest visitation rates. This is the first evidence showing that
      the behaviour of nearby pairs was affected away from an immediate source of risk.
      Our results indicate that the impacts of short-term predator encounters may
      immediately extend spatially to the broader community, affecting the behaviour of
      distant individuals. Information about predators is probably quickly spread by
      cues such as intra- and heterospecific alarm calls, in communities of different
      taxa. 

PMID- 27030412
TI  - Do community-weighted mean functional traits reflect optimal strategies?
AB  - The notion that relationships between community-weighted mean (CWM) traits (i.e.
      plot-level trait values weighted by species abundances) and environmental
      conditions reflect selection towards locally optimal phenotypes is challenged by
      the large amount of interspecific trait variation typically found within
      ecological communities. Reconciling these contrasting patterns is a key to
      advancing predictive theories of functional community ecology. We combined data
      on geographical distributions and three traits (wood density, leaf mass per area
      and maximum height) of 173 tree species in Puerto Rico. We tested the hypothesis
      that species are more likely to occur where their trait values are more similar
      to the local CWM trait values (the'CWM-optimality' hypothesis) by comparing
      species occurrence patterns (as a proxy for fitness) with the functional
      composition of forest plots across a precipitation gradient. While 70% of the
      species supported CWM-optimality for at least one trait, nearly 25% significantly
      opposed it for at least one trait, thereby contributing to local functional
      diversity. The majority (85%) of species that opposed CWM-optimality did so only
      for one trait and few species opposed CWM-optimality in multivariate trait space.
      Our study suggests that constraints to local functional variation act more
      strongly on multivariate phenotypes than on univariate traits.

PMID- 27030413
TI  - Palenque de San Basilio in Colombia: genetic data support an oral history of a
      paternal ancestry in Congo.
AB  - The Palenque, a black community in rural Colombia, have an oral history of
      fugitive African slaves founding a free village near Cartagena in the seventeenth
      century. Recently, linguists have identified some 200 words in regular use that
      originate in a Kikongo language, with Yombe, mainly spoken in the Congo region,
      being the most likely source. The non-recombining portion of the Y chromosome
      (NRY) and mitochondrial DNA were analysed to establish whether there was greater
      similarity between present-day members of the Palenque and Yombe than between the
      Palenque and 42 other African groups (for all individuals,n= 2799) from which
      forced slaves might have been taken. NRY data are consistent with the linguistic
      evidence that Yombe is the most likely group from which the original male
      settlers of Palenque came. Mitochondrial DNA data suggested substantial maternal
      sub-Saharan African ancestry and a strong founder effect but did not associate
      Palenque with any particular African group. In addition, based on cultural data
      including inhabitants' claims of linguistic differences, it has been hypothesized
      that the two districts of the village (Abajo and Arriba) have different origins,
      with Arriba founded by men originating in Congo and Abajo by those born in
      Colombia. Although significant genetic structuring distinguished the two from
      each other, no supporting evidence for this hypothesis was found. 

PMID- 27030414
TI  - Variation in relapse frequency and the transmission potential of Plasmodium vivax
      malaria.
AB  - There is substantial variation in the relapse frequency of Plasmodium vivax
      malaria, with fast-relapsing strains in tropical areas, and slow-relapsing
      strains in temperate areas with seasonal transmission. We hypothesize that much
      of the phenotypic diversity in P. vivax relapses arises from selection of relapse
      frequency to optimize transmission potential in a given environment, in a process
      similar to the virulence trade-off hypothesis. We develop mathematical models of
      P. vivax transmission and calculate the basic reproduction number R0 to
      investigate how transmission potential varies with relapse frequency and
      seasonality. In tropical zones with year-round transmission, transmission
      potential is optimized at intermediate relapse frequencies of two to three
      months: slower-relapsing strains increase the opportunity for onward transmission
      to mosquitoes, but also increase the risk of being outcompeted by faster
      relapsing strains. Seasonality is an important driver of relapse frequency for
      temperate strains, with the time to first relapse predicted to be six to nine
      months, coinciding with the duration between seasonal transmission peaks. We
      predict that there is a threshold degree of seasonality, below which fast
      relapsing tropical strains are selected for, and above which slow-relapsing
      temperate strains dominate, providing an explanation for the observed global
      distribution of relapse phenotypes.

PMID- 27030415
TI  - Almost a spider: a 305-million-year-old fossil arachnid and spider origins.
AB  - Spiders are an important animal group, with a long history. Details of their
      origins remain limited, with little knowledge of their stem group, and no
      insights into the sequence of character acquisition during spider evolution. We
      describe a new fossil arachnid, Idmonarachne brasierigen. et sp. nov. from the
      Late Carboniferous (Stephanian,ca 305-299 Ma) of Montceau-les-Mines, France. It
      is three-dimensionally preserved within a siderite concretion, allowing both
      laboratory- and synchrotron-based phase-contrast computed tomography
      reconstruction. The latter is a first for siderite-hosted fossils and has allowed
      us to investigate fine anatomical details. Although distinctly spider-like in
      habitus, this remarkable fossil lacks a key diagnostic character of Araneae:
      spinnerets on the underside of the opisthosoma. It also lacks a flagelliform
      telson found in the recently recognized, spider-related, Devonian-Permian
      Uraraneida. Cladistic analysis resolves our new fossil as sister group to the
      spiders: the spider stem-group comprises the uraraneids and I. brasieri While we
      are unable to demonstrate the presence of spigots in this fossil, the recovered
      phylogeny suggests the earliest character to evolve on the spider stem-group is
      the secretion of silk. This would have been followed by the loss of a
      flagelliform telson, and then the ability to spin silk using spinnerets. This
      last innovation defines the true spiders, significantly post-dates the origins of
      silk, and may be a key to the group's success. The Montceau-les-Mines locality
      has previously yielded a mesothele spider (with spinnerets). Evidently, Late
      Palaeozoic spiders lived alongside Palaeozoic arachnid grades which approached
      the spider condition, but did not express the full suite of crown-group
      autapomorphies.

PMID- 27030416
TI  - Oceanic dispersal, vicariance and human introduction shaped the modern
      distribution of the termites Reticulitermes, Heterotermes and Coptotermes.
AB  - Reticulitermes, Heterotermes and Coptotermes form a small termite clade with
      partly overlapping distributions. Although native species occur across all
      continents, the factors influencing their distribution are poorly known. Here, we
      reconstructed the historical biogeography of these termites using mitochondrial
      genomes of species collected on six continents. Our analyses showed that
      Reticulitermes split from Heterotermes + Coptotermesat 59.5 Ma (49.9-69.5 Ma 95%
      CI), yet the oldest split within Reticulitermes(Eurasia and North America) is
      16.1 Ma (13.4-19.5 Ma) and the oldest split within Heterotermes + Coptotermesis
      36.0 Ma (33.9-40.5 Ma). We detected 14 disjunctions between biogeographical
      realms, all of which occurred within the last 34 Ma, not only after the break-up
      of Pangaea, but also with the continents in similar to current positions. Land
      dispersal over land bridges explained four disjunctions, oceanic dispersal by
      wood rafting explained eight disjunctions, and human introduction was the source
      of two recent disjunctions. These wood-eating termites, therefore, appear to have
      acquired their modern worldwide distribution through multiple dispersal
      processes, with oceanic dispersal and human introduction favoured by the
      ecological traits of nesting in wood and producing replacement reproductives.

PMID- 27030417
TI  - Cohabitation promotes high diversity of clownfishes in the Coral Triangle.
AB  - Global marine biodiversity peaks within the Coral Triangle, and understanding how
      such high diversity is maintained is a central question in marine ecology. We
      investigated broad-scale patterns in the diversity of clownfishes and their host
      sea anemones by conducting 981 belt-transects at 20 locations throughout the Indo
      Pacific. Of the 1508 clownfishes encountered, 377 fish occurred in interspecific
      cohabiting groups and cohabitation was almost entirely restricted to the Coral
      Triangle. Neither the diversity nor density of host anemone or clownfish species
      alone influenced rates of interspecific cohabitation. Rather cohabitation
      occurred in areas where the number of clownfish species exceeds the number of
      host anemone species. In the Coral Triangle, cohabiting individuals were observed
      to finely partition their host anemone, with the subordinate species inhabiting
      the periphery. Furthermore, aggression did not increase in interspecific
      cohabiting groups, instead dominant species were accepting of subordinate
      species. Various combinations of clownfish species were observed cohabiting
      (independent of body size, phylogenetic relatedness, evolutionary age, dentition,
      level of specialization) in a range of anemone species, thereby ensuring that
      each clownfish species had dominant reproductive individuals in some cohabiting
      groups. Clownfishes are obligate commensals, thus cohabitation is an important
      process in maintaining biodiversity in high diversity systems because it supports
      the persistence of many species when host availability is limiting. Cohabitation
      is a likely explanation for high species richness in other obligate commensals
      within the Coral Triangle, and highlights the importance of protecting these
      habitats in order to conserve unique marine biodiversity. 

PMID- 27030418
TI  - Location-specific cuticular hydrocarbon signals in a social insect.
AB  - Social insects use cuticular hydrocarbons (CHCs) to convey different social
      signals, including colony or nest identity. Despite extensive investigations, the
      exact source and identity of CHCs that act as nest-specific identification
      signals remain largely unknown. Perhaps this is because studies that identify CHC
      signals typically use organic solvents to extract a single sample from the entire
      animal, thereby analysing a cocktail of chemicals that may serve several signal
      functions. We took a novel approach by first identifying CHC profiles from
      different body parts of ants (Iridomyrmex purpureus), then used behavioural
      bioassays to reveal the location of specific social signals. The CHC profiles of
      both workers and alates varied between different body parts, and workers paid
      more attention to the antennae of non-nest-mate and the legs of nest-mate
      workers. Workers responded less aggressively to non-nest-mate workers if the CHCs
      on the antennae of their opponents were removed with a solvent. These data
      indicate that CHCs located on the antennae reveal nest-mate identity and,
      remarkably, that antennae both convey and receive social signals. Our approach
      and findings could be valuably applied to chemical signalling in other
      behavioural contexts, and provide insights that were otherwise obscured by
      including chemicals that either have no signal function or may be used in other
      contexts. 

PMID- 27030419
TI  - Characterisation and expression analysis of trophozoite and cyst proteins of
      Acanthamoeba spp. isolated from Acanthamoeba keratitis (AK) patient.
AB  - The study was carried out to characterise and analyze the expression pattern of
      proteins of infective trophozoite and cyst forms of Acanthamoeba spp. isolated
      from an amoebic keratitis patient. Protein was isolated from the trophozoites and
      cysts of Acanthamoeba spp. isolates and subjected to SDS PAGE, 2D PAGE analysis
      where a large number of protein bands and protein spots were observed. Four
      prominent protein spots i.e. 2 from trophozoites and 2 from cysts that appeared
      more intense compared to the corresponding spots in other corresponding gel were
      excised from the 2D PAGE gels and analysed by MALDI-TOF/TOF MS assay and Mascot
      search software. Protein spots from trophozoites were identified as "hypothetical
      protein ACA1" and "eukaryotic porin protein" and those from cysts were identified
      as "chaperone protein DnaK" and "chaperonin protein" respectively. Proteomic
      results of 4 proteins were further validated by reverse genomics using
      quantitative real time PCR assay which showed a 1388 fold and 4.35 fold increase
      in expression of "hypothetical protein ACA1" gene and "eukaryotic porin protein"
      gene respectively in trophozoites compared to cysts and a 15 fold and 12.36 fold
      increase in expression of "chaperone protein DnaK" gene and "chaperonin protein"
      gene respectively in cysts compared to trophozoites. "Hypothetical protein ACA1"
      of trophozoites, whose function is unknown might have some important role in the
      parasite division and pathogenicty of Acanthamoeba spp. which needs further
      study. As trophozoites are the active and feeding form of Acanthamoeba spp.,
      "eukaryotic porin" proteins may have some important role in efflux of toxic
      metabolites and exudates from interior of cell to outside along with some role in
      pathogenicity. Similarly proteins such as "chaperone protein DnaK" and
      "chaperonin protein" which belongs to group of heat shock proteins may have a
      role in folding of cyst specific proteins in cyst which needs further study. 

PMID- 27030420
TI  - A strategy for absolute proteome quantification with mass spectrometry by
      hierarchical use of peptide-concatenated standards.
AB  - The accurate and precise absolute abundance of proteins can be determined using
      mass spectrometry by spiking the sample with stable isotope-labeled standards. In
      this study, we developed a strategy of hierarchical use of peptide-concatenated
      standards (PCSs) to quantify more proteins over a wider dynamic range. Multiple
      primary PCSs were used for quantification of many target proteins. Unique "ID-tag
      peptides" were introduced into individual primary PCSs, allowing us to monitor
      the exact amounts of individual PCSs using a "secondary PCS" in which all "ID-tag
      peptides" were concatenated. Furthermore, we varied the copy number of the "ID
      tag peptide" in each PCS according to a range of expression levels of target
      proteins. This strategy accomplished absolute quantification over a wider range
      than that of the measured ratios. The quantified abundance of budding yeast
      proteins showed a high reproducibility for replicate analyses and similar copy
      numbers per cell for ribosomal proteins, demonstrating the accuracy and precision
      of this strategy. A comparison with the absolute abundance of transcripts clearly
      indicated different post-transcriptional regulation of expression for specific
      functional groups. Thus, the approach presented here is a faithful method for the
      absolute quantification of proteomes and provides insights into biological
      mechanisms, including the regulation of expressed protein abundance.

PMID- 27030421
TI  - Patent Ductus Arteriosus and Brain Volume.
AB  - BACKGROUND AND OBJECTIVES: A hemodynamically significant patent ductus arteriosus
      (PDA) can compromise perfusion and oxygenation of the preterm brain. Reports
      suggest that PDA is associated with increased mortality and morbidity. We
      hypothesize that long-standing low cerebral oxygenation due to PDA might affect
      brain volume at term equivalent age. METHODS: Observational study in 140 infants
      investigating the relationship between near-infrared spectroscopy-monitored
      cerebral oxygen saturation (rSco2) and MRI-assessed regional brain volume and
      maturation of the posterior limb of the internal capsule at term-equivalent age
      in 3 groups: those whose PDA closed with indomethacin, those who needed
      additional surgical closure, and matched controls. RESULTS: The surgery group had
      the lowest rSco2 values before closure (n = 35), 48% +/- 9.7% (mean +/- SD) as
      compared with the indomethacin (n = 35), 59% +/- 10.4 (P < .001), and control
      groups (n = 70), 66% +/- 6.9 (P < .001); the highest postnatal age before
      effective treatment; and the lowest volumes of most brain regions at term
      equivalent age. Multiple linear regression analysis showed a significant effect
      of preductal closure rSco2 on cerebellar volume in this group. No differences
      were found in maturation of the posterior limb of the internal capsule.
      CONCLUSIONS: Long-standing suboptimal cerebral oxygenation due to a PDA may
      negatively influence brain growth, affecting neurodevelopmental outcome.

PMID- 27030422
TI  - Patent Ductus Arteriosus and the Immature Brain: Is Early Intervention
      Protective?

PMID- 27030423
TI  - Respiratory Rate During the First 24 Hours of Life in Healthy Term Infants.
AB  - BACKGROUND AND OBJECTIVE: Abnormal respiratory rate (RR) is a key symptom of
      disease in the newborn. The aim of this study was to establish the reference
      range for RR during the first 24 hours of life in healthy infants born at term.
      METHODS: Infants were included at the hospital postnatal ward when time
      permitted. During sleep or a defined quiet state, RR was counted at 2, 4, 8, 16,
      and 24 hours by placing the bell of a stethoscope in front of the nostrils and
      mouth for 60 seconds. Data on maternal health, pregnancies, and births were
      obtained from medical records and the Medical Birth Registry of Norway. RESULTS:
      The study included 953 infants. Median RRs were 46 breaths/minute at 2 hours,
      thereafter 42 to 44 breaths/minute. The 95th percentile was 65 breaths/minute at
      2 hours, thereafter 58 to 60 breaths/minute. The fifth percentile was 30 to 32
      breaths/minute. Within these limits, the intraindividual variation was wide. The
      overall mean RR was 5.2 (95% confidence interval [CI], 4.7 to 5.7, P < .001)
      breaths/minute higher while awake than during sleep, 3.1 (95% CI, 1.5 to 4.8, P <
      .001) breaths/minute higher after heavy meconium staining of the amniotic fluid,
      and 1.6 (95% CI, 0.8 to 2.4, P < .001) breaths/minute higher in boys than girls.
      RR did not differ for infants born after vaginal versus cesarean deliveries.
      CONCLUSIONS: The RR percentiles established from this study allow for a
      scientifically based use of RR when assessing newborn infants born at term.

PMID- 27030424
TI  - Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility
      to hypertension and additive diseases: A study on North Indian patients.
AB  - Angiotensin-converting enzyme (ACE) is the key enzyme of the renin angiotensin
      system (RAS) which maintains the blood pressure homeostasis in our body. The
      association of the ACE insertion/deletion (I/D) polymorphism with essential
      hypertension has been demonstrated by many studies. The purpose of the present
      study is to investigate the association of the insertion/deletion polymorphism of
      the ACE gene with hypertension and additive diseases in North Indian population.
      In total, 222 hypertensive and 218 normotensive adults participated in this
      hospital-based study. Anthropometric measures, lipids profiles, blood glucose,
      and blood pressure (BP) measures were collected from participants. ACE I/D
      polymorphism was determined by using insertion-specific amplification. The mean
      ages of study groups were 50.35 +/- 12.40 and 47.32 +/- 11.94 for cases and
      controls, respectively. Significant differences were observed in the frequencies
      of DD, ID, and II genotypes among the hypertensive and normotensive groups which
      were found to be 29.7%, 38.7%, and 31.5% vs. 53.7%, 23.4%, and 22.9%,
      respectively. It has been observed that the ACE ID genotype was significantly (p
      < 0.05) higher in hypertensive subjects, whereas, the DD genotype was
      significantly (p < 0.05) higher in control subjects. A strong association was
      found between cardiovascular diseases (CVDs) and ID genotype [p = 0.017, odds
      ratio (OR) = 3.091, 95% confidence interval (CI) = 1.224-7.807]. ID [p = 0.002,
      OR = 2.020, 95% CI = 1.281-3.185] and II [p = 0.032, OR = 1.677, 95% CI = 1.044
      2.694] genotypes are more prone to diabetes with hypertension. This finding
      suggests that ACE insertion/deletion polymorphism is associated with hypertension
      and additive diseases in North Indians. 

PMID- 27030426
TI  - The edge of chaos: A nonlinear view of psychoanalytic technique.
AB  - The field of nonlinear dynamics (or chaos theory) provides ways to expand
      concepts of psychoanalytic process that have implications for the technique of
      psychoanalysis. This paper describes how concepts of "the edge of chaos,"
      emergence, attractors, and coupled oscillators can help shape analytic technique
      resulting in an approach to doing analysis which is at the same time freer and
      more firmly based in an enlarged understanding of the ways in which
      psychoanalysis works than some current recommendation about technique.
      Illustrations from a lengthy analysis of an analysand with obsessive-compulsive
      disorder show this approach in action. 

PMID- 27030425
TI  - Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal
      transition.
AB  - Epithelial cells form spatially-organized adhesion complexes that establish
      polarity gradients, regulate cell proliferation, and direct wound healing. As
      cells accumulate oncogenic mutations, these key tumor suppression mechanisms are
      disrupted, eliminating many adhesion complexes and bypassing contact inhibition.
      The transcription factor Snail is often expressed in malignant cancers, where it
      promotes transcriptional reprogramming to drive epithelial-mesenchymal transition
      (EMT) and establishes a more invasive state. S-Palmitoylation describes the fatty
      acyl post-translational modification of cysteine residues in proteins, and is
      required for membrane anchoring, trafficking, localization and function of
      hundreds of proteins involved in cell growth, polarity, and signaling. Since
      Snail-expression disrupts apico-basolateral cell polarity, we asked if Snail
      dependent transformation induces proteome-wide changes in S-palmitoylation.
      MCF10A breast cancer cells were retrovirally transduced with Snail and correlated
      proteome-wide changes in protein abundance and S-palmitoylation were profiled by
      using stable isotope labeling in cell culture with amino acid (SILAC) mass
      spectrometry. This analysis identified increased levels of proteins involved in
      migration, glycolysis, and cell junction remodeling, and decreased levels of
      proteins involved in cell adhesion. Overall, protein S-palmitoylation is highly
      correlated with protein abundance, yet for a subset of proteins, this correlation
      is uncoupled. These findings suggest that Snail-overexpression affects the S
      palmitoylation cycle of some proteins, which may participate in cell polarity and
      tumor suppression.

PMID- 27030427
TI  - [. Role of molecular and genetic factors in survival from uveal melanoma].
AB  - AIM: to analyze survival rates in uveal melanoma (UM) patients and establish
      correlations with chromosome 3 monosomy, chromosome 1p deletion, and RASSF1A
      methylation. MATERIAL AND METHODS: Methylation-specific PCR analysis was
      performed in 104 patients with histologically verified UM. RESULTS: A
      statistically significant correlation has been found between chromosome 3
      monosomy, on the one hand, and mixed/epithelioid cell melanomas and ciliary body
      involvement, on the other. As for chromosome 1p deletion, it has demonstrated
      association with extrabulbar tumor growth. We have also calculated 5-year
      survival and mortality rates in "large" UMs and their relationship with
      chromosome 3 monosomy, chromosome 1p deletion, and RASSF1A methylation.
      CONCLUSION: Chromosome 3 monosomy is associated with lower survival rates, while
      RASSF1A methylation - with a better prognosis. A combination of molecular and
      genetic changes (particularly, chromosome 3 monosomy and chromosome 1p deletion)
      also leads to reduced survival in UM patients.

PMID- 27030428
TI  - [CFH gene polymorphism in primary open-angle glaucoma patients].
AB  - AIM: to study the CFH T402H polymorphism in glaucoma patients and controls.
      MATERIAL AND METHODS: Genetic analysis was performed in 68 patients with primary
      open-angle glaucoma (POAG) of various severity. The control group consisted of 30
      participants. Venous whole blood samples were obtained. From them, leukocytes
      were isolated and human genomic DNA extracted for further PCR. RESULTS: None of
      the patients from either group was homozygous for the 402H allele. With ganglion
      cells death (i.e. at later stages of the disease), the percentage of homozygotes
      that carry no CFH polymorphism increases up to 65%, while that of heterozygotes
      decreases down to 35%. CONCLUSION: As shown, most of early and advanced POAG
      patients are heterozygotes. At these stages of the disease own ganglion cells are
      very likely to be damaged. Further progression, however, is associated with a
      gradual decrease in heterozygotes (down to 35%) due to a substantial loss of
      neuroepithelial cells and suppression of the autoimmune response which has lost
      its target.

PMID- 27030430
TI  - [Step-by-step creation of internal limiting membrane fragment for surgical
      treatment of large idiopathic macular holes].
AB  - AIM: to develop a surgical procedure for large idiopathic macular holes (MH) that
      would involve creation of an original internal limiting membrane (ILM) flap to
      close the hole with. MATERIAL AND METHODS: Nineteen patients aged from 59 to 71
      years with stage 3 idiopathic MH (by J. Gass) were enrolled. Besides standard
      ophthalmic examination, spectral optical coherence tomography and microperimetry
      were performed in all cases. The patients were followed up 2 weeks and then 1 and
      3 months after surgery. Surgical procedure was notable for an original ILM flap
      created in a way that resembles removing petals from a flower. The new method
      implies that the ILM is peeled off all the way round the MH except for the
      foveolar area and one particular ILM fragment, which is only partially separated
      from the retina, from the periphery towards the MH, stopping at some 0.1-0.2 mm
      from its margin. This last fragment is then inverted to cover the MH. RESULTS:
      All surgeries were completed without complications. Visual acuity has gradually
      increased over the follow-up period in all patients: from 0.1-0.4 to 0.3-0.7
      (0.39+/-0.15 on the average; Sivtsev-Golovin chart). Foveal anatomy has also
      improved: complete closure of the MH was achieved in 8 patients, partial - in 11.
      Moreover, all patients demonstrated a shift of the retinal fixation point towards
      the center of the fovea for 153-369 mm, at that, their fixation has stabilized
      and absolute central scotomas disappeared. CONCLUSION: The method developed is a
      promising treatment for large idiopathic macular holes. Further studies are
      required.

PMID- 27030429
TI  - [Uveitis: RESULTS of a prospective randomized clinical and immunological study].
AB  - AIM: to evaluate the RESULTS of a randomized prospective clinical and
      immunological study conducted during 2012-2014 in patients with uveitis. MATERIAL
      AND METHODS: The main group consisted of 200 randomly selected patients with
      uveitis including 114 men (57%) and 86 women (42%) aged 19-57 years. A
      comprehensive ophthalmic and immunological examination was performed in all
      patients regardless of them having a relapse or remission. To assess patient's
      immune status, we investigated parameters of cellular and humoral immunity as
      well as complement components C3 and C4 levels. RESULTS: Systemic connective
      tissue disorders appeared to be the main cause of uveitis among the patients
      examined - 32% of cases. But if to consider distinct nosological entities, first
      place goes to herpes virus infection - 22% of cases. In general, infectious
      uveitis was diagnosed in 43.5% of cases, underlying systemic conditions were
      found in other 46%, and finally, in some patients, uveitis was identified as
      posttraumatic (4.5%) or idiopathic (6%). A total of 60.5% of patients showed
      clinical and functional improvement under treatment. Irreversible blindness in 9
      patients was due to one of the following: secondary glaucoma (4 cases, 2%),
      retinal detachment (3 cases, 1.5%), or ocular subatrophy (2 cases, 1%). Late
      referral (i.e. after the development of irreversible secondary complications)
      should be named as one of the main causes of low vision in patients with uveitis.
      As to laboratory changes, only those in cellular and congenital immunity factors
      were statistically significant. CONCLUSION: In order to minimize the risk of
      proliferative secondary complications, a tool should be created such as a single
      database of uveitis patients, according to which they could be followed up. Long
      term immunosuppressive therapy for uveitis may lead to herpesvirus reactivation.
      The complex nature of immune disorders justifies certain corrective measures in
      uvetis patients but only with account to their current immune status.

PMID- 27030431
TI  - [Lacrimal and salivatory glycoproteins in ophthalmic herpes].
AB  - AIM: to compare tear, saliva, and plasma levels of acute phase proteins (APPs) of
      inflammation in patients with herpes keratitis and to use the RESULTS in
      treatment evaluation. MATERIAL AND METHODS: APPs were measured in tears, oral
      fluid, and blood plasma from 22 adults and 34 children with ophthalmic herpes as
      well as 68 healthy controls using immunoturbidimetric and spectrophotometric
      methods of detection. RESULTS: High levels of C-reactive protein and orosomucoid,
      low levels of ceruloplasmin, alpha1-antitrypsin, and transferrin in tears from
      patients with herpes keratitis as well as abnormal tear, saliva, and plasma APPs
      levels at discharge are poor prognostic signs. They all indicate that corneal
      inflammation is still intense and that the treatment should not be ceased yet.
      Severity of APPs concentration changes in tear from patients with herpes
      keratitis correlates with the depth of corneal lesions, recurrence rate, and
      disease dynamics. CONCLUSION: Quantitative determination of acute phase proteins
      in tear and oral fluid is an early and sensitive inflammation test and may be
      also used for non-invasive monitoring and antiviral treatment evaluation. Oral
      fluid allows to extend the capabilities of non-invasive diagnostics of ophthalmic
      herpes.

PMID- 27030432
TI  - [Distinctive morphological and functional changes in retinal ganglion cells
      associated with normal aging and early stage of glaucoma].
AB  - Early diagnosis of primary open-angle glaucoma (POAG) is closely connected with
      detection of normal age-related changes in the retina. It is also essential to
      develop reliable methods for quantitative evaluation of retinal nerve fiber layer
      (RNFL) thickness and retinal ganglion cells (RGCs) structure and function as well
      as to extend opportunities for inter-instrumental comparisons. AIM: to assess the
      function of RGCs from parvo- and magnocellular pathways by means of pattern
      electroretinography and to evaluate the degree of retinal sensitivity loss and
      RNFL thickness using new methods of analysis in normal aging and the early stage
      of POAG. MATERIAL AND METHODS: Four groups were formed: group 1 - young healthy
      participants, group 2 - aged controls, group 3 - glaucoma suspects, and group 4 -
      early-stage POAG patients. In all groups we investigated the MD and PSD indices
      of static computer perimetry (HEP, Heidelberg Edge Perimeter, SAP and FDF tests)
      and RNFL thickness provided by HRT III (Heidelberg Engineering). Pattern
      electroretinograms (PERGs) were recorded with the RETImap system (Roland Consult)
      at the check sizes of 0.8 degrees  and 16 degrees . For steady-state and
      transient PERGs the 0.8 degrees /16 degrees  and N95/P50 ratios were calculated,
      respectively. RESULTS: There was a statistically significant difference in PERG
      amplitudes to 0.8 degrees  checks (p=0.0001) and in 0.8 degrees /16 degrees 
      ratios (p=0.0001) between the groups 1 and 2. Differences between the groups 2
      and 3 as well as 3 and 4 were statistically significant only as to 0.8 degrees 
      checks (p=0.03 and p=0.001, respectively). Responses to 16 degrees  checks were
      alike in all groups. We have also applied original formulas to determine the
      relative loss of RGCs and their axons and the congruence coefficient for
      morphological and functional parameters in normal aging and the early stage of
      POAG. CONCLUSION: The discovered age-related PERG changes convincingly indicate a
      greater parvocellular RGC loss as compared to magnocellular. Thus, the PERG ratio
      (0.8 degrees /16 degrees ) should be corrected for the subject's age. The
      proposed indices of relative decline in retinal light sensitivity and RNFL
      thinning have been shown to be useful for quantifying the loss of RGC bodies and
      axons in normal aging and early-stage glaucoma.

PMID- 27030433
TI  - [Bandwidth measurement technique for spatial frequency channels in human visual
      system].
AB  - AIM: to determine the number of measurements required to obtain stable bandwidth
      values for spatial frequency channels (SFCs) in the human visual system. MATERIAL
      AND METHODS: Ten untrained, normal vision subjects 18-22 years old were presented
      with light pulses (flickers) with initial frequency of 10 Hz and then with a
      higher-than-initial and lower-than-initial frequency alternately at 1-sec
      intervals. The difference between flickers frequencies was gradually increased
      until the test subject determined his/her discrimination threshold. This
      threshold was assumed to represent the SFC bandwidth. Measured values were
      plotted on a coordinate system "SFC bandwidth - the number of measurement". The
      described procedure was repeated and a graph resulted showing SFC bandwidth as a
      function of Ni, where Ni is the number of i-th measurement and i = 1, 2, ..., k
      (k - the sequence number of measurement at which the transition process was
      completed and a quasi-stationary state achieved): DeltaF=f(Ni). The number of
      measurements required to obtain stable SFC bandwidth values was determined from
      the number of measurements made during the transition process. RESULTS: It has
      been found that to obtain stable bandwidth values for SFCs of the human visual
      system, 2 to 8 measurements are required (point estimate of the median for the
      given sample equaled 5). CONCLUSION: The duration of a transition process to
      stable SFC bandwidth values is individual and this should be taken into account
      when assessing the visual system.

PMID- 27030435
TI  - [Technique for surgical repositioning of in-the-bag dislocated intraocular
      lenses].
AB  - AIM: to develop and test a new technique for surgical repositioning of in-the-bag
      dislocated intraocular lenses (IOLs). MATERIAL AND METHODS: Surgical outcomes of
      21 patients with in-the-bag IOL dislocation were analyzed (follow-up period 1-12
      years). RESULTS: The proposed method of IOL-capsular bag complex fixation with
      two double sutures provides a reliable anatomic and functional result.
      CONCLUSION: The new technique enables surgical repositioning of in-the-bag
      dislocated IOLs following trauma in patients who have not had an intracapsular
      ring implanted before.

PMID- 27030434
TI  - [Morphological assessment of lens capsule after different techniques of cataract
      extraction].
AB  - AIM: to evaluate morphological changes in the posterior lens capsule (LC) after
      different techniques of cataract extraction. MATERIAL AND METHODS: Eight
      pseudophakic human autopsy eyes were divided into two groups by the technique
      used for cataract extraction. Group 1 included 4 eyes following extracapsular
      cataract extraction (ECCE) and rigid IOL implantation. Group 2 included 4 eyes
      after minimally invasive cataract surgery (MICS) that involves the use of
      ultrasound energy. Semithin LC sections were polychromatically stained, visually
      examined, and imaged for further analysis. RESULTS: There were certain common
      features in clinical and morphological appearances of lens capsules from either
      group, including fibrous metaplasia of epithelial cells and/or pseudoregenerative
      Elschnig-Adamuk pearls on their inner surfaces, more significant in the ECCE
      group. MICS group, however, demonstrated many distinct and previously undescribed
      changes. In particular, post-MICS LCs looked swollen, flabby, and even amorphous,
      their architectonics were disturbed and fibers separated forming micro slit-like
      spaces, which could be a result of acoustic cavitation caused by ultrasound
      exposure. We have named this morphological type of secondary cataract "hyaloid
      like". CONCLUSION: Clinical and morphological type of postoperative LC
      opacification as well as its severity depends, to a certain extent, on the
      technique used for cataract extraction. Hyaloid-like opacifications are typical
      of minimally invasive surgery involving the use of ultrasound and often show no
      'classic' changes (fibroproliferative and pseudoregenerative). The latter is
      explained by the fact that the posterior LC, which has lost its biomechanical
      properties, can no longer be a substrate for proliferating cells.

PMID- 27030436
TI  - [Effectiveness of femtosecond laser assistance in complicated cataracts].
AB  - AIM: to perform comparative evaluation of intra- and postoperative clinical
      RESULTS in patients with complicated cataracts (grade I-II lens subluxation,
      pseudoexfoliation syndrome, or surgically treated glaucoma) undergoing either
      standard or femtosecond laser-assisted phacoemulsification. MATERIAL AND METHODS:
      A total of 197 patients (245 eyes) aged 32-85 years (58.5 years on average) with
      complicated cataracts were divided into two groups by the technique used for
      phacoemulsification. Group 1 (main group, 120 eyes of 105 patients) underwent
      femtosecond laser-assisted phacoemulsification. Group 2 (controls, 125 eyes of 92
      patients) received standard procedures. Subjective and objective measures of
      ocular structure and function were evaluated in 1, 3, and 7 days and 1 month
      after the surgery. RESULTS: In the femtosecond laser-assisted group, all lenses
      were well-centered in the capsular bag as documented by ultrasound biomicroscopy.
      During the whole follow-up period the studied parameters were stable. No
      dislocations occurred. In group 2 (standard phaco), all parameters demonstrated
      high changeability over the follow-up period. CONCLUSION: The improved technique
      of femtosecond laser-assisted phacoemulsification offers many advantages to
      surgical management of complicated cataracts. Not only does it allow to reduce
      ultrasound time, but also to perform precise capsulorhexis with preset
      parameters, decrease intra- and postoperative complications rates, and improve
      refraction outcomes in such patients.

PMID- 27030437
TI  - [Antioxidants in complex treatment of far-advanced open-angle glaucoma].
AB  - AIM: to evaluate treatment RESULTS in far-advanced glaucoma patients. MATERIAL
      AND METHODS: A total of 81 patients (81 eyes) with far-advanced open-angle
      glaucoma were followed up. The patients were divided into two groups by the
      treatment they received. In group 1 (41 patients, 41 eyes) a complex treatment
      scheme was applied, which included surgical, medicinal, and physiotherapeutic
      measures, in particular, sinus trabeculectomy (STE) plus posterior scleral
      trepanation (PST), a 10-day course of subconjunctival Cytoflavin 10 mg 0.5 ml,
      and magnetolaser stimulation of the optic nerve. Group 2 (controls) consisted of
      the rest 40 patients (40 eyes), who received just STE and PST. RESULTS: The
      combination approach has yielded visual improvements and glaucoma stabilization
      in 87% of patients from group 1 by the end of the first year of follow-up, while
      in group 2 positive changes were found in only 68% of patients.

PMID- 27030438
TI  - [Cyanocobalamin-containing lubricant for topical therapy of LASIK-associated dry
      eye].
AB  - AIM: to study the effect of topical treatment with Artelac Balance, a
      cyanocobalamin-containing lubricant, in patients with post-LASIK corneal
      neuropathy and LASIK-associated dry eye. MATERIAL AND METHODS: Patients scheduled
      for LASIK were enrolled. Inclusion criteria were contact lens wear for 5 years or
      longer and more than 6 diopters of myopia. The patients were divided into 3
      groups. Group 1 was prescribed the cyanocobalamin-containing topical lubricant
      for 3 months before and 1 month after surgery, group 2 - the same cyanocobalamin
      containing lubricant, but only for the first month after surgery, and group 3
      received a standard preservative-free lubricant for the first month after
      surgery. Tear osmolarity and production as well as corneal sensitivity were
      assessed 90+/-10 days before and 30+/-3 days after surgery. The percentage of
      patients with dry eye symptoms and those who required prolonged use of lubricants
      were also estimated at day 30+/-3. RESULTS: Preoperatively, there were no
      statistically significant differences in demographic characteristics, tear
      osmolarity, tear production, or corneal sensitivity between the three study
      groups. At day 30+/-3 after surgery, tear production and corneal sensitivity were
      both significantly higher in group 1 than in group 3 (16.8 mm vs. 13.2 mm,
      p=0.003 and 37.7+/-3.1 mm vs. 32.4+/-2.2 mm, p=0.023, respectively). As to the
      percentage of patients with dry eye symptoms and those who required prolonged use
      of lubricants, it was lower in group 1 than in group 3 (51.3% vs. 76.3%, p=0.03
      and 38.5% vs. 63.2%, p=0.03, respectively). Between the groups 2 and 3, none of
      the studied parameters differed significantly. CONCLUSION: Combined pre- and
      postoperative use of Artelac Balance, a cyanocobalamin-containing lubricant, has
      been proved effective in restoring corneal sensitivity and reducing dry eye
      symptoms in patients at high risk for developing LASIK-associated dry eye.

PMID- 27030439
TI  - [Long-term outcomes of anti-angiogenic therapy for macular neovascular
      disorders].
AB  - AIM: to study long-term (>=2-year) RESULTS of ranibizumab treatment in patients
      with macular neovascular disorders. MATERIAL AND METHODS: The study group
      included 27 patients (mean age+/-SD of 66.7+/-13.8 years) treated with
      ranibizumab for approved indications. Follow-up period ranged from 24 to 58
      months (34.5+/-9.1 months on average). RESULTS: Optical coherence tomography
      showed statistically significant improvements of functional and anatomical
      parameters, namely, an increase in visual acuity (from 0.34+/-0.20 to 0.57+/
      0.24, p<=0.01) and a decrease in both central retinal thickness (from 372.26+/
      96.21 MUm to 272.48+/-69.70 MUm, p<=0.01) and macular volume (from 8.01+/-1.46
      mm3 to 7.10+/-1.08 mm3, p<=0.01). There was also a decreasing tendency of the
      average annual number of intravitreal ranibizumab injections per patient: 4.56
      injections were done during the 1st year, 1.93 - during the 2nd year, and only
      1.6 - during the 3rd year of follow-up. A total of 29.6% of patients showed no
      need in resuming the treatment at year 2 and 40.0% - at year 3. Exudation from
      the neovascular membrane relapsed in 24 patients (88.9%) at some time during the
      follow-up; at that, in 74.1% of patients the injection-free intervals lasted from
      6 to 36 months. None of the 231 injections was associated with any complications
      concerning ocular functions and morphology and requiring additional treatment. No
      correlation was found between the anti-angiogenic therapy and the progression of
      cardiovascular disease. CONCLUSION: Intravitreal ranibizumab has been proved
      effective and safe for the treatment of neovascular macular disorders. Moreover,
      flexible dosing schemes for ranibizumab contribute to rapid (during the 1st year
      already) and stable clinical benefits.

PMID- 27030440
TI  - Biotechnology and synthetic biology approaches for metabolic engineering of
      bioenergy crops.
AB  - The Green Revolution has fuelled an exponential growth in human population since
      the mid-20th century. Due to population growth, food and energy demands will soon
      surpass supply capabilities. To overcome these impending problems, significant
      improvements in genetic engineering will be needed to complement breeding efforts
      in order to accelerate the improvement of agronomical traits. The new field of
      plant synthetic biology has emerged in recent years and is expected to support
      rapid, precise, and robust engineering of plants. In this review, we present
      recent advances made in the field of plant synthetic biology, specifically in
      genome editing, transgene expression regulation, and bioenergy crop engineering,
      with a focus on traits related to lignocellulose, oil, and soluble sugars.
      Ultimately, progress and innovation in these fields may facilitate the
      development of beneficial traits in crop plants to meet society's bioenergy
      needs.

PMID- 27030441
TI  - One-Pot Synthesis of Benzo[4,5]imidazo[2,1-a]isoquinolines and Isoquinolino[3,4
      b]quinoxalines via Tandem Cyclization Strategies.
AB  - Two operationally simple one-pot protocols have been developed for the synthesis
      of amino-functionalized benzo[4,5]imidazo[2,1-a]isoquinolines and
      isoquinolino[3,4-b]quinoxalines. Optimization data and substrate scope for these
      atom-economical transformations, which engage commercially available o
      phenylenediamines and o-cyanobenzaldehydes, are discussed.

PMID- 27030442
TI  - Topological vacuum bubbles by anyon braiding.
AB  - According to a basic rule of fermionic and bosonic many-body physics, known as
      the linked cluster theorem, physical observables are not affected by vacuum
      bubbles, which represent virtual particles created from vacuum and self
      annihilating without interacting with real particles. Here we show that this
      conventional knowledge must be revised for anyons, quasiparticles that obey
      fractional exchange statistics intermediate between fermions and bosons. We find
      that a certain class of vacuum bubbles of Abelian anyons does affect physical
      observables. They represent virtually excited anyons that wind around real
      anyonic excitations. These topological bubbles result in a temperature-dependent
      phase shift of Fabry-Perot interference patterns in the fractional quantum Hall
      regime accessible in current experiments, thus providing a tool for direct and
      unambiguous observation of elusive fractional statistics. 

PMID- 27030443
TI  - Grandmother's 41 secrets: The curious secret art of women, by Carol Ann Spiller
      Parsky.

PMID- 27030445
TI  - Nitinol clip distal migration and resultant popliteo-tibial artery occlusion
      complicating access closure by the StarClose SE vascular closure system.
AB  - Lower extremity ischemia following deployment of a vascular closure device for
      access site closure after a transfemoral endovascular procedure rarely occurs. A
      68-year-old woman diagnosed with subarachnoid hemorrhage due to a ruptured
      anterior communicating aneurysm was treated by endovascular coil embolization.
      The StarClose SE device was deployed for right femoral arteriotomy closure. After
      2 days, critical ischemia occurred on her right lower leg due to total occlusion
      of the popliteo-tibial artery. Emergent surgical embolectomy was performed and
      the nitinol clip of the StarClose device was captured in the lumen of the
      tibioperoneal trunk. Although StarClose is an extravascular closure system,
      intravascular deployment, distal migration, and resultant critical limb ischemia
      can occur.

PMID- 27030444
TI  - Influence of cigarette smoking on cardiac biomarkers: the Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - AIMS: Cigarette smoking has been associated with incident heart failure
      independent of coronary artery disease (CAD), but the mechanisms linking smoking
      to cardiac damage are not well understood. This study sought to evaluate the
      relationship between smoking and N-terminal pro-brain natriuretic peptide (NT
      proBNP) and high-sensitivity Troponin T (hs-TnT), which are, respectively,
      biomarkers of myocardial wall stress and injury, in a large community-based
      cohort. METHODS AND RESULTS: We examined the association between smoking history
      and NT-proBNP and hs-TnT in 9649 participants free of overt CAD or heart failure
      from the Atherosclerosis Risk in Communities (ARIC) Study who attended Visit 4
      (1996-1998), as well as the association with change in these biomarkers from
      Visit 4 to Visit 5 (2011-2013) in 3151 participants. At Visit 4, higher
      cumulative cigarette exposure, assessed by total pack-years, was associated with
      elevated levels of NT-proBNP (P < 0.001) and hs-TnT (P = 0.01) among ever smokers
      in multivariable analyses adjusted for potential confounders. After 15 years of
      follow-up, participants who were active smokers at Visit 4 had greater incidence
      of elevated NT-proBNP {adjusted proportion = 48% [95% confidence interval (CI)
      41, 54] vs. 35 (95% CI 32, 39); P = 0.006} and hs-TnT [adjusted proportion = 32%
      (95% CI 26, 38) vs. 23 (95% CI 20, 26); P = 0.021] compared with never smokers,
      adjusting for baseline and follow-up covariates. CONCLUSIONS: In a large
      community-based cohort free of overt CAD and heart failure, cigarette smoking was
      associated with biomarkers of myocardial wall stress and injury at baseline as
      well as with a continued measurable increase in these biomarkers after 15 years
      of follow-up.

PMID- 27030446
TI  - An unusual aetiology of back pain.
AB  - We present the case of a healthy young man who developed pyogenic myositis, an
      infection that is rare in the USA. He had no prior medical conditions except for
      an obsessive-compulsive disorder and skin picking disorder resulting in multiple
      superficial skin infections. He presented to our hospital with acute back pain.
      He was found to be septic with fever, tachycardia and elevated white cell counts.
      Imaging revealed evidence of myositis in the gluteal region. He was treated with
      antibiotics and fully recovered. It is likely that the skin picking disorder and
      the recurrent superficial skin infections are responsible for the development of
      this infection. 

PMID- 27030447
TI  - Xanthogranulomatous pancreatitis mimicking a malignant solid tumour.
AB  - Xanthogranulomatous inflammation, which is known to occur in several viscera, is
      rarely found to affect the pancreas. We report a case of xanthogranulomatous
      pancreatitis (XGP) occurring in a 60-year-old man who presented with epigastric
      pain and vomiting. Physical examination did not reveal any abnormality. Contrast
      enhanced CT of the abdomen revealed an ill-defined, heterogeneous mass lesion in
      the uncinate process of the pancreas, suggestive of malignancy. Whipple's
      pancreaticoduodenectomy was performed and the final pathological diagnosis was
      XGP. The patient's postoperative course was uneventful. When a pancreatic mass
      does not show clinicoradiological features typical of common pancreatic
      neoplasms, XGP should be considered for a differential diagnosis and duodenum
      preserving surgery can be considered. 

PMID- 27030448
TI  - Ileocolic intussusception in a premature neonate.

PMID- 27030449
TI  - Adult onset primary focal dystonia of the foot: an orthopaedic intervention.
AB  - A 54-year-old woman presented to a foot centre with a chief symptom of cramping
      in her toes, which, she believed, was of a secondary cause originating from a
      bunion. She was treated conservatively; however, she returned a month later as
      the symptoms had progressed to painful cramping of toes, toe-curling and
      instability while walking, due to involuntary movement of her toes. It was
      believed that the patient presented with a rare case of primary adult onset focal
      foot dystonia. This case report explains dystonia further in detail and delves
      into the different treatment and management options available today, including
      the unique orthopaedic intervention provided for this patient. 

PMID- 27030451
TI  - Clinical diagnostic dilemma in an uncharacteristic rapidly enlarging swelling of
      the anterior maxilla: extranodal diffuse large B cell lymphoma.
AB  - Extranodal non-Hodgkin lymphoma (NHL) is infrequent in the oral cavity and
      constitutes 3.5% of oral cancers, and less than 2.2% of maxillofacial lymphomas.
      Diffuse large B cell lymphoma (DLBCL) accounts for 40% of NHL and has a 5-year
      survival rate of less than 30%. Early detection of extranodal NHL by dental
      personnel is extremely important as a delay in diagnosis can result in the cancer
      being diagnosed at an advanced stage and a poor prognosis. A 60-year-old male
      presented with an uncharacteristic asymptomatic rapidly enlarging swelling of the
      anterior maxilla, which on histopathological and immunohistochemical analysis was
      diagnosed as DLBCL. Imaging studies showed bone invasion and lymph node
      metastasis with poor prognosis. The patient received radiotherapy and
      chemotherapy but died within 3 months of diagnosis. A literature search revealed
      one another case with anterior maxilla occurrence, as the few oral DLBCL so far
      reported have appeared on the posterior palate or other intraoral sites.

PMID- 27030450
TI  - Free-floating thrombus in a stenotic supraclinoid left internal carotid artery.

PMID- 27030452
TI  - Recurrent vomiting in a woman due to miscarriage: think out of the box.
AB  - A 25-year-old gravida 2 para 1 with 12-week amenorrhoea presented a second time
      for recurrent vomiting in pregnancy. She was diagnosed to have a missed
      miscarriage following absent fetal heart seen in an early scan. She opted for
      conservative management. However, on the third presentation, her vomiting
      continued. Repeated transvaginal ultrasound scan showed a fetus with a crown rump
      length of 19 mm, which is equivalent to 8 weeks and 4 days, with absence of fetal
      heart pulsation. Thyroid function tests and beta human chorionic gonadotropin
      were then requested. Results showed that the patient's serum beta human chorionic
      gonadotropin level was markedly raised to 147,000. A molar pregnancy was
      suspected. Her thyroid function tests came back normal. Suction curettage was
      performed and histopathology confirmed a partial molar pregnancy. On follow-up,
      the beta human chorionic gonadotropin level was normal by 7 weeks after the
      curettage.

PMID- 27030454
TI  - Correction.

PMID- 27030455
TI  - Nasogastric tube check, easy or not?

PMID- 27030453
TI  - Impella-assisted transcatheter closure of an acute postinfarction ventricular
      septal defect.
AB  - This case report describes a 72-year-old woman who developed an acute
      postmyocardial infarction ventricular septal defect (VSD) with consequent
      cardiogenic shock. Intra-aortic balloon pump (IABP) counter-pulsation was
      urgently initiated in the cardiac catheterisation laboratory, with neither
      clinical nor haemodynamic improvement, prompting immediate removal of the IABP
      and the insertion of an Impella 2.5 heart pump (AbioMed Inc; Danvers,
      Massachusetts, USA), a temporary ventricular assist device. Thereafter, the
      patient improved clinically and was admitted to the cardiovascular intensive care
      unit (ICU). While in the cardiovascular ICU, the patient developed worsening
      mechanical haemolysis of blood cells, stable but persistent cardiogenic shock and
      a transient ischaemic attack. A consensus decision was made to proceed with
      percutaneous repair of the VSD as she was deemed at high risk for surgical
      repair. She underwent successful percutaneous VSD repair on day 4 of
      hospitalisation, using a single 18 mm Amplatzer muscular VSD occluder (AGA
      Medical, Plymouth, Minnesota, USA) with trace residual flow across the occluder.
      Adequate systolic blood pressure and cardiac output was maintained postprocedure
      with the Impella 2.5 device. The patient, however, succumbed to multiorgan
      dysfunction occasioned by sepsis.

PMID- 27030456
TI  - Familial florid osseous dysplasia: a report with review of the literature.
AB  - There are three types of osseous dysplasia: periapical cemental dysplasia (PCD),
      focal cemento-osseous dysplasia (FCD) and florid osseous dysplasia (FOD). While
      PCD is often observed in mandibular anterior teeth, FCD mainly affects mandibular
      posterior teeth. FOD, on the other hand, commonly involves both jaws. FOD is a
      type of sclerosing disease that is characterised by intense opaque masses and
      many areas with different densities. Genetic heritance of FOD is unusual, with
      only a few reported cases. We describe a case of FOD that affected three family
      members, discuss its clinical, radiological and histological characteristics, and
      review the literature.

PMID- 27030457
TI  - Unusual organism causing pyocystis in an immunosuppressed haemodialysis patient.
AB  - A 68-year-old man with end-stage renal disease and a history of orthotopic
      cardiac transplantation on chronic immune suppression therapy presented to the
      emergency department with fever and purulent urethral discharge. He was diagnosed
      with pyocystis (bladder abscess). Culture of the urethral discharge
      showedTrueperella bernardiae The patient improved after 3 days of bladder
      irrigation with normal saline and gentamicin. This case demonstrates that bladder
      abscess is a potential source of infection in an oliguric patient. This is the
      first report to describe the opportunistic pathogen,T. bernardiae, as the
      causative agent in pyocystis.

PMID- 27030458
TI  - Atypical case of ecthyma gangrenosum mimicking a breast cancer recurrence.
AB  - A 68-year-old woman with a history of breast cancer presented with skin lesions
      and sternal pain. Clinical examination revealed ulcerative lesions on mastectomy
      scar and CT scan showed contiguous sternal osteolysis. The main hypothesis was a
      breast cancer recurrence; however, cutaneous and bone biopsies did not reveal any
      cancer cells. Skin tissue culture detected Pseudomonas aeruginosa, suggesting
      ecthyma gangrenosum despite the absence of bacteraemia in our patient and despite
      her immunocompetence. Surgical treatment was performed, followed by a long course
      of antibiotherapy.

PMID- 27030459
TI  - West Nile virus-associated brachial plexopathy.
AB  - West Nile virus (WNV) is the most frequent cause of arbovirus infection in the
      USA. Only 20% of infected individuals are symptomatic. Less than 1% of
      symptomatic individuals display West Nile neuroinvasive disease. We report a rare
      case of WNV-associated brachial plexopathy in a young immunocompetent individual,
      without cerebrospinal fluid pleocytosis or encephalitis. Additionally, there was
      subjective and objective improvement after high-dose corticosteroids. This case
      adds to the clinical spectrum of WNV neuroinvasive disease. The literature
      regarding immunomodulatory treatment and WNV is reviewed. 

PMID- 27030460
TI  - DRESS syndrome potentially induced by allopurinol and triggered by influenza
      vaccine.
AB  - Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, also
      known as drug-induced hypersensitivity syndrome (DHIS), is an acute, potentially
      life-threatening disease that includes skin rash, fever, haematological
      abnormalities and multiorgan involvement. Although its aetiopathogenesis is not
      exactly known, it is thought that inefficient drug detoxification leading to the
      accumulation of drug reactive metabolites causes autoimmune responses in skin and
      some internal organs, alters immune responses and induces reactivation of viral
      infections in people who have genetic predisposition. To the best of our
      knowledge, only one case of DRESS syndrome has been reported after delivery of
      the influenza vaccine, but the drug that induced the reaction in that case was
      sulfasalazine. We report a case of a 64-year-old woman, receiving allopurinol,
      who developed DRESS syndrome after taking the influenza vaccine. 

PMID- 27030461
TI  - Emergency abdominal wall defects in neonates: saved by distress.
AB  - This report presents two cases of neonatal patients with abdominal wall defects
      requiring emergency intervention, a closing gastroschisis and a pedunculated
      exomphalos with eviscerated liver. Both presented as pre-partum fetal distress
      and were delivered in a tertiary centre, where they received antenatal care.
      Coordination in the multidisciplinary team and prompt surgical intervention
      prevented loss of the eviscerated abdominal contents and prevented mortality in
      both cases. 

PMID- 27030462
TI  - Bilateral ureteric stones: an unusual cause of acute kidney injury.
AB  - A 49-year-old man presented to the accident and emergency department, with a
      short history of vague abdominal pain, abdominal distension and two episodes of
      frank haematuria. A plain chest film showed dilated loops of large bowel and
      blood results on admission showed an acute kidney injury (stage 3). A diagnosis
      of bowel obstruction was made initially but a CT scan of the abdomen showed
      bilateral obstructing calculi. After initial resuscitation, the patient had
      bilateral ultrasound-guided nephrostomies and haemofiltration. He later underwent
      bilateral antegrade ureteric stenting. A decision will later be made on whether
      or not he is fit enough to undergo ureteroscopy and laser stone fragmentation. 

PMID- 27030463
TI  - Pseudo tumour appearance of vulvar varicose veins.

PMID- 27030464
TI  - Impact of curative surgery on bone in a patient with osteitis fibrosa cystica of
      primary hyperparathyroidism.

PMID- 27030465
TI  - Isolated common iliac artery dissection and aneurysm.

PMID- 27030466
TI  - Micronutrient content in enteral nutrition formulas: comparison with the dietary
      reference values for healthy populations.
AB  - BACKGROUND: The micronutrient content in standard enteral mixtures should be
      closer to the dietary reference values for a healthy population since standard
      enteral diets are formulated for subjects with no special nutritional needs. This
      study compares the micronutrient content of the most common enteral nutrition
      (EN) formulas with European dietary reference values (DRVs) for healthy
      population. FINDINGS: Sixty-two nutritionally complete enteral formulas were
      considered. The micronutrient content was calculated by multiplying the value
      reported on the nutritional information panel of each formula by the daily dose
      usually prescribed. The comparison between the micronutrient content of all
      enteral formulas evaluated and the DRVs indicates that daily fluoride and vitamin
      K requirements were not covered, while an oversupply of many other micronutrients
      was provided. Moreover, in some enteral formulas, at a dose of 2000 Kcal/day,
      zinc and vitamin A content exceeded the tolerable upper limits and, for one
      diabetes-specific enteral formula, the chromium content exceeded the relevant
      European standards in both 1500 and 2000 Kcal/day diets. CONCLUSIONS: Most
      enteral formulas evaluated are generally suitable for patients on long-term total
      EN and formulas with higher content of a specific micronutrient may be a useful
      tool for patients affected by specific clinical conditions, at least for a period
      of time, then switching to standard enteral mixtures. The availability of
      nutritional enteral formulas, well balanced also for micronutrient intake, will
      further improve individualized treatments, particularly for patients on long-term
      total EN.

PMID- 27030467
TI  - Doctors are failing to help people with gender dysphoria.

PMID- 27030468
TI  - Gd-DTPA Adsorption on Chitosan/Magnetite Nanocomposites.
AB  - The synthesis of the chitosan/magnetite nanocomposites is presented. Composites
      were prepared by co-precipitation of iron(II) and iron(III) salts by aqueous
      ammonia in the 0.1 % chitosan solution. It was shown that magnetite synthesis in
      the chitosan medium does not affect the magnetite crystal structure. The thermal
      analysis data showed 4.6 % of mass concentration of chitosan in the hybrid
      chitosan/magnetite composite. In the concentration range of initial Gd-DTPA
      solution up to 0.4 mmol/L, addition of chitosan to magnetite increases the
      adsorption capacity and affinity to Gd-DTPA complex. The Langmuir and Freundlich
      adsorption models were applied to describe adsorption processes. Nanocomposites
      were characterized by scanning electron microscopy (SEM), differential thermal
      analysis (DTA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction
      (XRD), and specific surface area determination (ASAP) methods. 

PMID- 27030469
TI  - Insight to Nanoparticle Size Analysis-Novel and Convenient Image Analysis Method
      Versus Conventional Techniques.
AB  - The aim of this paper is to introduce a new image analysis program
      "Nanoannotator" particularly developed for analyzing individual nanoparticles in
      transmission electron microscopy images. This paper describes the usefulness and
      efficiency of the program when analyzing nanoparticles, and at the same time, we
      compare it to more conventional nanoparticle analysis techniques. The techniques
      which we are concentrating here are transmission electron microscopy (TEM) linked
      with different image analysis methods and X-ray diffraction techniques. The
      developed program appeared as a good supplement to the field of particle analysis
      techniques, since the traditional image analysis programs suffer from the
      inability to separate the individual particles from agglomerates in the TEM
      images. The program is more efficient, and it offers more detailed morphological
      information of the particles than the manual technique. However, particle shapes
      that are very different from spherical proved to be problematic also for the
      novel program. When compared to X-ray techniques, the main advantage of the small
      angle X-ray scattering (SAXS) method is the average data it provides from a very
      large amount of particles. However, the SAXS method does not provide any data
      about the shape or appearance of the sample. 

PMID- 27030470
TI  - Using the Diffusion Model to Explain Cognitive Deficits in Attention Deficit
      Hyperactivity Disorder.
AB  - Slow, variable, and error-prone performance on speeded reaction time (RT) tasks
      has been well documented in childhood ADHD, but equally well documented is the
      context-dependent nature of those deficits, particularly with respect to event
      rate. As event rates increase (or, as the interstimulus intervals become
      shorter), RTs decrease, a pattern of performance that has long been interpreted
      as evidence that cognitive deficits in ADHD are a downstream consequence of a
      fundamental difficulty in the regulation of arousal to meet task demands. We test
      the extent to which this is a misinterpretation of the data that occurs when RT
      and accuracy are considered separately, as is common in neurocognitive research.
      In two samples of children aged 8-10 with (N = 97; 33 girls) and without (N = 39;
      26 girls) ADHD, we used the diffusion model, an influential computational model
      of RT, to examine the effect of event rate on inhibitory control in a go-no-go
      task. Contrary to longstanding belief, we found that fast event rates slowed the
      rate at which children with ADHD accumulated evidence to make a decision to "no
      go", as indexed by drift rate. This in turn resulted in a higher proportion of
      failed inhibits, and occurred despite increased task engagement, as reflected by
      changes in the starting point of the decision process. Thus, although faster
      event rates increased task engagement among children with ADHD, the increased
      engagement was unable to counteract the concurrent slowing of processing speed to
      "no-go" decisions. Implications for theoretical models of ADHD and treatments are
      discussed.

PMID- 27030471
TI  - Simple reaction time and size-distance integration in virtual 3D space.
AB  - Simple reaction time to visual stimuli depends on several stimulus properties.
      Recently, converging evidence showed that larger stimulus size evokes faster
      reactions and that this effect seemingly depends on the stimulus' perceived size
      rather than on physical stimulus properties. Size-distance scaling usually is
      regarded as the main functional mechanism underlying size perception. Yet, the
      role of stimulus depth (distance to a target) has often been neglected in
      previous studies. Hence, in the present investigation, stimuli were generated
      using stereo head mounted displays to manipulate stimulus depth. In Experiment 1,
      a large or small target was presented within the center of a reference plane,
      either in the same depth plane or displaced (near, far) while participants had to
      perform a simple reaction time task. At the same time, the target was modulated
      such that either retinal size was constant or variable across depth planes. In
      Experiments 2 and 3 the reference plane was shifted along with the target
      (blocked or on a trial-by-trial basis), while retinal size modulation was equal
      to Experiment 1. As expected, participants reacted faster to physically larger
      targets. Also Experiment 1 revealed faster reaction times for closer targets,
      while the commonly described connection between perceived size (i.e., size
      distance scaling) was not apparent in any experiment. Thus, unlike past findings
      using a virtual three-dimensional task-setting (as induced by binocular
      disparity) reaction times are not affected by variations of perceived stimulus
      size.

PMID- 27030472
TI  - Mapping training needs for dissemination and implementation research: lessons
      from a synthesis of existing D&I research training programs.
AB  - With recent growth in the field of dissemination and implementation (D&I)
      research, multiple training programs have been developed to build capacity,
      including summer training institutes, graduate courses, degree programs,
      workshops, and conferences. While opportunities for D&I research training have
      expanded, course organizers acknowledge that available slots are insufficient to
      meet demand within the scientific and practitioner community. In addition,
      individual programs have struggled to best fit various needs of trainees,
      sometimes splitting coursework between specific D&I content and more introductory
      grant writing material. This article, stemming from a 2013 NIH workshop, reviews
      experiences across multiple training programs to align training needs, career
      stage and role, and availability of programs. We briefly review D&I needs and
      opportunities by career stage and role, discuss variations among existing
      training programs in format, mentoring relationships, and other characteristics,
      identify challenges of mapping needs of trainees to programs, and present
      recommendations for future D&I research training.

PMID- 27030473
TI  - Deeper understanding of the role of dopamine in reward, learning, and motivation.

PMID- 27030475
TI  - High-performance photodetectors and enhanced photocatalysts of two-dimensional
      TiO2 nanosheets under UV light excitation.
AB  - Due to the large surface area-to-volume ratio and rapid electron transfer, two
      dimensional (2D) TiO2 nanosheets with ultrathin thicknesses are synthesized by
      using a bottom-up strategy and these self-assembled nanosheet (NS)-based
      photocatalysts and photodetectors were explored for the first time. The influence
      of calcination temperature on microstructures and photocatalytic activity of TiO2
      nanosheets were discovered and presented. The as-obtained TiO2 nanosheets were
      characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) analysis,
      Fourier transform infrared (FTIR) spectroscopy, UV-vis spectrophotometry, and X
      ray photoelectron spectroscopy (XPS). The following heat treatment process
      induced phase evolution from rutile to anatase. The TiO2 nanosheets calcined at
      500  degrees C exhibited the best activity for photo-degradation of organic dyes
      under UV light irradiation. The obtained photodetector exhibits excellent
      performance with a high photocurrent to dark current ratio and fast response and
      recovery times. Additionally, we demonstrated that the device may have potential
      applications in the future low-power optoelectronics system. 

PMID- 27030474
TI  - Whole genome sequencing in cats, identifies new models for blindness in AIPL1 and
      somite segmentation in HES7.
AB  - BACKGROUND: The reduced cost and improved efficiency of whole genome sequencing
      (WGS) is drastically improving the development of cats as biomedical models.
      Persian cats are models for Leber's congenital amaurosis (LCA), the most severe
      and earliest onset form of visual impairment in humans. Cats with innocuous breed
      defining traits, such as a bobbed tail, can also be models for somite
      segmentation and vertebral column development. METHODS: The first WGS in cats was
      conducted on a trio segregating for LCA and the bobbed tail abnormality. Variants
      were identified using FreeBayes and effects predicted using SnpEff. Variants
      within a known haplotype block for cat LCA and specific candidate genes for both
      phenotypes were prioritized by the predicted variant effect on the proteins and
      concordant segregation within the trio. The efficiency of WGS of a single trio of
      domestic cats was evaluated. RESULTS: A stop gain was identified at position
      c.577C > T in cat AIPL1, a predicted p.Arg193*. A c.5A > G variant causing a
      p.V2A was identified in HES7. The variants segregated concordantly in a Persian -
      Japanese bobtail pedigree. Over 1700 cats from 40 different breeds and
      populations were genotyped for the AIPL1 variant, defining an allelic frequency
      in only Persian -related breeds of 1.15%. A sub-set of cats was genotyped for the
      HES7 variant, supporting the variant as private to the Japanese bobtail breed.
      Approximately 18 million SNPs were identified for application in cat research.
      The cat AIPL1 variant would have been considered a high priority variant for
      evaluation, regardless of a priori knowledge from previous genetic studies.
      CONCLUSIONS: This study represents the first effort of the 99 Lives Cat Genome
      Sequencing Initiative to identify disease--causing variants in the domestic cat
      using WGS. The current cat reference assembly is efficient for gene and variant
      identification. However, as the feline variant database improves, development of
      cats as biomedical models for human disease will be more efficient, providing an
      alternative, large animal model for drug and gene therapy trials. Undiagnosed
      human patients with early-onset blindness should be screened for this AIPL1
      variant. The HES7 variant should further calibrate the somite segmentation clock.

PMID- 27030477
TI  - What's the point of tobacco control? Comment on Dan Halliday, 'The ethics of a
      smoking licence'.

PMID- 27030476
TI  - Functional assay of antiplatelet drugs based on margination of platelets in
      flowing blood.
AB  - A novel functional assay of antiplatelet drug efficacy was designed by utilizing
      the phenomena of platelet margination in flowing blood and transient platelet
      contacts with surface-immobilized platelet agonists. Flow margination enhances
      transient contacts of platelets with the walls of flow chambers covered with
      surface-immobilized proteins. Depending on the type and the surface density of
      the immobilized agonists, such transient interactions could "prime" the
      marginated platelet subpopulation for enhanced activation and adhesion
      downstream. By creating an upstream surface patch with an immobilized platelet
      agonist, platelet flow margination was used to test how effective antiplatelet
      drugs are in suppressing downstream platelet activation and adhesion. The
      platelet adhesion downstream was measured by a so-called "capture" patch region
      close to the distal end of the flow chamber. Platelet adhesion downstream was
      found to be dose-dependent on the upstream surface coverage of the "priming"
      patch, with immobilized fibrinogen acting as a platelet agonist. Several
      antiplatelet agents (acetylsalicylic acid, eptifibatide, and tirofiban) were
      evaluated for their efficacy in attenuating downstream adhesion after upstream
      platelet priming. The activation of the platelet population was found to be
      dependent on both the extent of the upstream agonist stimulus and the
      antiplatelet drug concentration. Such a relationship provides an opportunity to
      measure the efficacy of specific antiplatelet agents against the type and
      concentration of upstream platelet agonists. 

PMID- 27030478
TI  - Conceptualising well-being for autistic persons.
AB  - In the philosophy of well-being, there is hardly anything written on the lives of
      people with autism or on the question whether existing philosophical theories of
      well-being are suited for understanding how well the lives of autistic persons
      are going. This paper tries to make some progress towards filling this gap. I
      start by giving a concise account of autism, which highlights the huge
      heterogeneity among autistics. I discuss some basic features of autism, ask
      whether there are good reasons why we would need an account of well-being
      specifically for autistics and what philosophical well-being research could learn
      from being informed by autistic experiences and phenomenology. I then investigate
      to what extent the capability approach gives us a helpful theory of well-being
      for autistics, and what looking through an autism-lens can contribute to the
      further development of the capabilitarian well-being. In particular, I show that
      some capabilities that are crucially relevant for autistics are also relevant for
      the lives of non-autistic people. The final part of the paper looks at an
      important difficulty in using the capabilitarian account of well-being for
      autistics, namely: should the normative focus be on achievements (functionings)
      or real opportunities (capabilities)?

PMID- 27030479
TI  - The right to public health.
AB  - Much work in public health ethics is shaped by an 'autonomy first' view, which
      takes it to be axiomatic that it is difficult to justify state interference in
      the lives of competent adults unless the behaviours interfered with are
      compromised in terms of their autonomy, or would wrongfully infringe on the
      autonomy of others. However, such an approach is difficult to square with much of
      traditional public heath practice. Recent years have seen running battles between
      those who assume that an 'autonomy first' approach is basically sound (and so
      much the worse for public health practice) and those who assume that public
      health practice is basically sound (and so much the worse for the 'autonomy
      first' approach). This paper aims to reconcile in a normatively satisfying way
      what is best about the 'autonomy first' approach with what is best about a
      standard public health approach. It develops a positive case for state action to
      promote and protect health as a duty that is owed to each individual. According
      to this view, the state violates individuals' rights if it fails to take cost
      effective and proportionate measures to remove health threats from the
      environment. It is thus a mistake to approach public health in the way that
      'autonomy first' accounts do, as primarily a matter of individual entitlements
      versus the common good. Too little state intervention in the cause of improving
      population health can violate individuals' rights, just as too much can.

PMID- 27030480
TI  - Killing or letting die? Proposal of a (somewhat) new answer to a perennial
      question.
AB  - There is as yet no widely agreed-upon solution to the standard textbook problem
      whether actively shutting off a life-sustaining medical device, e.g. a
      respirator, and thus bringing about a patient's death amounts to active killing
      or just to an omission of further treatment. Apart from a range of astutely
      contrived case examples and respective particular solutions proposed in the
      literature, there seems to be no consensus on the normative principles such
      solutions should be grounded in, not even on the need for such principles beyond
      sheer intuition. The present paper attempts to develop a normative approach based
      on fundamental principles of law. From this perspective, what is decisive for the
      question of 'killing or letting die' in such cases is not that death ensues from
      a behaviour that is active and relevantly causative, but rather, whether or not
      the agent in performing the deadly act transgresses the boundaries of the domain
      of his or her sole normative authority, and thereby intervenes in the protected
      sphere of another. Unless he or she does so, their behaviour cannot be classified
      as active commission regardless of the amount of causal activity it may display
      and regardless of its potentially harmful consequences. This conception is
      spelled out in detail and tested in a range of case examples, as are several of
      its corollaries that deviate from standard type solutions.

PMID- 27030481
TI  - The case for banning cigarettes.

PMID- 27030482
TI  - What is wrong with the emergency justification of compulsory medical service?
AB  - Michael Blake holds that liberal states are precluded from introducing compulsory
      medical service to improve access to health care under conditions of critical
      health worker shortage. "Emergency circumstances" are the only exception when the
      suspension of liberty may be justified. I argue that there are three problems
      with Blake's emergency justification of compulsory service. First, his concept of
      emergency is vague. Second, his account does not really rely on emergency as much
      as liberty. Third, his conception of permissible restrictions of liberty is too
      narrow. I argue that liberties may be limited to some degree, temporarily, for
      the sake of attaining the capacities necessary for the exercise of liberties and
      for safeguarding the social conditions of the right to health. I conclude that in
      poor societies, temporarily delaying emigration through a highly qualified
      compulsory medical service can sometimes be justified.

PMID- 27030483
TI  - Premortem interventions in dying children to optimise organ donation: an ethical
      analysis.
AB  - A range of interventions in dying patients can improve both the possibility of
      successful organ donation and the likely long-term success of transplantation.
      The ethical and legal issues surrounding such interventions, which most
      frequently occur in the context of donation after circulatory determination of
      death, are complex, controversial and many remain unresolved. This is true with
      adults, but even more so with children, where the issue of organ donation and
      premortem interventions to facilitate it, are highly sensitive. Essentially, such
      interventions are being undertaken in dying children who cannot medically benefit
      from them, though arguments have been advanced that becoming a donor might be in
      a child's extended best interest. However, certain interventions carry a
      potential risk, although small, of direct harm and of course overall objections
      to child donation after circulatory determination of death per se are still
      expressed in the literature. But, unlike the case in critically ill adults, those
      giving permission for such interventions are normally able to fully participate
      in decision-making, and indeed to consent, to both donation and premortem
      interventions. We review the issue of the use of premortem interventions in dying
      children to facilitate organ donation, including decision-making and ethical
      justification. Individual interventions are then considered, including an ethical
      analyse of their use. Finally, we recommend an approach using a combination of
      welfare checklist strategy, coupled with the establishment of an agreed zone of
      parental discretion about individual interventions which might be used in dying
      children to increase the possibility of successful organ donation.

PMID- 27030484
TI  - Can facilitated aid in dying be permitted by 'double effect'? Some reflections
      from a recent New Zealand case.
AB  - While the Doctrine of Double Effect (DDE) remains controversial in ethical
      circles, it continues to be recognised in common law courts. In 2015, the High
      Court of New Zealand became the latest to acknowledge the existence of the DDE,
      in a case that challenged the prohibition on physician assisted dying. In so
      doing, the possibility was raised that the DDE could potentially be used in an
      untraditional way to provide a prima facie justification of "facilitated aid in
      dying" (FAID) in some cases.In this article, we develop and offer justification
      for this line of reasoning. If it can be shown that FAID sometimes satisfies the
      conditions for DDE, this, we suggest, may have significant implications for the
      aid in dying debate, not only in New Zealand, but more widely. Even if all of the
      elements of the DDE are not met in such cases, though, we suggest that one of
      those elements - the doctor's intent in providing FAID - may not always be such
      as to attract moral blame or criminal culpability.

PMID- 27030485
TI  - Photosensitive Peptidomimetic for Light-Controlled, Reversible DNA Compaction.
AB  - Light-induced DNA compaction as part of nonviral gene delivery was investigated
      intensively in the past years, although the bridging between the artificial light
      switchable compacting agents and biocompatible light insensitive compacting
      agents was not achieved until now. In this paper, we report on light-induced
      compaction and decompaction of DNA molecules in the presence of a new type of
      agent, a multivalent cationic peptidomimetic molecule containing a photosensitive
      Azo-group as a branch (Azo-PM). Azo-PM is synthesized using a solid-phase
      procedure during which an azobenzene unit is attached as a side chain to an
      oligo(amidoamine) backbone. We show that within a certain range of concentrations
      and under illumination with light of appropriate wavelengths, these cationic
      molecules induce reversible DNA compaction/decompaction by photoisomerization of
      the incorporated azobenzene unit between a hydrophobic trans- and a hydrophilic
      cis-conformation, as characterized by dynamic light scattering and AFM
      measurements. In contrast to other molecular species used for invasive DNA
      compaction, such as widely used azobenzene containing cationic surfactant (Azo
      TAB, C4-Azo-OCX-TMAB), the presented peptidomimetic agent appears to lead to
      different complexation/compaction mechanisms. An investigation of Azo-PM in close
      proximity to a DNA segment by means of a molecular dynamics simulation sustains a
      picture in which Azo-PM acts as a multivalent counterion, with its rather large
      cationic oligo(amidoamine) backbone dominating the interaction with the double
      helix, fine-tuned or assisted by the presence and isomerization state of the Azo
      moiety. However, due to its peptidomimetic backbone, Azo-PM should be far less
      toxic than photosensitive surfactants and might represent a starting point for a
      conscious design of photoswitchable, biocompatible vectors for gene delivery.

PMID- 27030486
TI  - Reduced Diagnostic Performance of Two Norovirus Antigen Enzyme Immunoassays for
      the Emergent Genogroup II Genotype 17 Kawasaki 2014 Variant.
AB  - Two commonly used norovirus enzyme immunoassays have reduced diagnostic
      performance, with clinical sensitivities ranging from 11% to 35% for the
      detection of the recently emerging genogroup II genotype 17 (GII.17) Kawasaki
      2014 variant that caused the majority of infections in Asia during the winter of
      2014 to 2015. False-negative results can compromise infection control and patient
      management.

PMID- 27030487
TI  - GenoType NTM-DR for Identifying Mycobacterium abscessus Subspecies and
      Determining Molecular Resistance.
AB  - We studied the performance of a new line probe assay for identifying the
      subspecies and determining the macrolide and aminoglycoside resistance levels of
      50 Mycobacterium abscessus isolates. Agreement of GenoType NTM-DR results with
      sequencing and phenotypic resistance results was 92% for subspecies
      identification and 98% for determining molecular and phenotypic resistance.

PMID- 27030488
TI  - Anatomic, Geographic, and Taxon-Specific Relative Risks of Carbapenem Resistance
      in the Health Care System of the U.S. Department of Defense.
AB  - Carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter spp., and
      Enterobacteriaceae pose urgent public health threats. The differential burden,
      relative risks, associations with antimicrobial consumption, and temporal trends
      of those taxa in large, geographically diverse U.S. health systems remain under
      reported. Electronic records of all patients in a geographically dispersed 280
      hospital managed-care system from 2005 to 2014 were reviewed. Carbapenem
      resistant strains were identified based on Clinical and Laboratory Standards
      Institute guidelines and breakpoints. A total of 360,000 potentially carbapenem
      resistant strains were identified from 14.7 million cultures (80% infecting and
      20% surveillance). Isolation of bacteria overseas or isolation from the
      bloodstream was associated with a higher relative risks of carbapenem resistance
      (CR; P < 0.0001). Enterobacteriaceae were isolated 11 times more frequently than
      P. aeruginosa and Acinetobacter spp. However, compared to Enterobacteriaceae, the
      CR levels were 73-fold and 210-fold higher in P. aeruginosa and Acinetobacter
      spp., respectively. Significant differences in the relative risk of CR between
      taxa, anatomic, and geographic locations persisted after adjustment for other
      variables, the biggest differences occurring between taxa. Overall, CR rates
      increased for Enterobacteriaceae (P = 0.03) and decreased for Acinetobacter spp.
      and P. aeruginosa (P < 0.0001). These data provide a useful baseline for
      resistance trending and have implications for surveillance. Infections acquired
      overseas and bloodstream infections are particularly important areas for
      continued monitoring.

PMID- 27030489
TI  - Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and
      Houseflies.
AB  - Senecavirus A (SVA) is an emerging picornavirus that has been recently associated
      with an increased number of outbreaks of vesicular disease and neonatal mortality
      in swine. Many aspects of SVA infection biology and epidemiology remain unknown.
      Here, we present a diagnostic investigation conducted in swine herds affected by
      vesicular disease and increased neonatal mortality. Clinical and environmental
      samples were collected from affected and unaffected herds and were screened for
      the presence of SVA by real-time reverse transcriptase PCR and virus isolation.
      Notably, SVA was detected and isolated from vesicular lesions and tissues of
      affected pigs, environmental samples, mouse feces, and mouse small intestine. SVA
      nucleic acid was also detected in houseflies collected from affected farms and
      from a farm with no history of vesicular disease. Detection of SVA in mice and
      housefly samples and recovery of viable virus from mouse feces and small
      intestine suggest that these pests may play a role on the epidemiology of SVA.
      These results provide important information that may allow the development of
      improved prevention and control strategies for SVA.

PMID- 27030490
TI  - Antimicrobial-Loaded Bone Cement Does Not Negatively Influence Sonicate Fluid
      Culture Positivity for Diagnosis of Prosthetic Joint Infection.
AB  - We compared culture results to investigate the influence of antimicrobial-loaded
      cement on sonicate fluid culture positivity for the diagnosis of prosthetic joint
      infection. Fifty-four subjects were assessed. The sensitivities of sonicate fluid
      culture were 77.8% (14 of 18) in subjects with an antimicrobial-loaded cemented
      prosthesis and 58.3% (21 of 36) in subjects with an antimicrobial-free
      prosthesis.

PMID- 27030491
TI  - Commutability of Cytomegalovirus WHO International Standard in Different
      Matrices.
AB  - Commutability of quantitative standards allows patient results to be compared
      across molecular diagnostic methods and laboratories. This is critical to
      establishing quantitative thresholds for use in clinical decision-making. A
      matrix effect associated with the 1st cytomegalovirus (CMV) WHO international
      standard (IS) was identified using the Abbott RealTime CMV assay. A commutability
      study was performed to compare the CMV WHO IS and patient specimens diluted in
      plasma and whole blood. Patient specimens showed similar CMV DNA quantitation
      values regardless of the diluent or extraction procedure used. The CMV WHO IS, on
      the other hand, exhibited a matrix effect. The CMV concentration reported for the
      WHO IS diluted in plasma was within the 95% prediction interval established with
      patient samples. In contrast, the reported DNA concentration of the CMV WHO IS
      diluted in whole blood was reduced approximately 0.4 log copies/ml, and values
      fell outside the 95% prediction interval. Calibrating the assay by using the CMV
      WHO IS diluted in whole blood would introduce a bias for CMV whole-blood
      quantitation; samples would be reported as having higher measured concentrations,
      by approximately 0.4 log IU/ml. Based on the commutability study with patient
      samples, the RealTime CMV assay was standardized based on the CMV WHO IS diluted
      in plasma. A revision of the instructions for use of the CMV WHO IS should be
      considered to alert users of the potential impact from the diluent matrix. The
      identification of a matrix effect with the CMV WHO IS underscores the importance
      of assessing commutability of the IS in order to achieve consistent results
      across methods.

PMID- 27030492
TI  - A Pan-Dengue Virus Reverse Transcription-Insulated Isothermal PCR Assay Intended
      for Point-of-Need Diagnosis of Dengue Virus Infection by Use of the POCKIT
      Nucleic Acid Analyzer.
AB  - Dengue virus (DENV) infection is considered a major public health problem in
      developing tropical countries where the virus is endemic and continues to cause
      major disease outbreaks every year. Here, we describe the development of a novel,
      inexpensive, and user-friendly diagnostic assay based on a reverse transcription
      insulated isothermal PCR (RT-iiPCR) method for the detection of all four
      serotypes of DENV in clinical samples. The diagnostic performance of the newly
      established pan-DENV RT-iiPCR assay targeting a conserved 3' untranslated region
      of the viral genome was evaluated. The limit of detection with a 95% confidence
      was estimated to be 10 copies of in vitro-transcribed (IVT) RNA. Sensitivity
      analysis using RNA prepared from 10-fold serial dilutions of tissue culture fluid
      containing DENVs suggested that the RT-iiPCR assay was comparable to the
      multiplex real-time quantitative RT-PCR (qRT-PCR) assay for DENV-1, -3, and -4
      detection but 10-fold less sensitive for DENV-2 detection. Subsequently, plasma
      collected from patients suspected of dengue virus infection (n = 220) and
      individuals not suspected of dengue virus infection (n = 45) were tested by the
      RT-iiPCR and compared to original test results using a DENV NS1 antigen rapid
      test and the qRT-PCR. The diagnostic agreement of the pan-DENV RT-iiPCR, NS1
      antigen rapid test, and qRT-PCR tests was 93.9%, 84.5%, and 97.4%, respectively,
      compared to the composite reference results. This new RT-iiPCR assay along with
      the portable POCKIT nucleic acid analyzer could provide a highly reliable,
      sensitive, and specific point-of-need diagnostic assay for the diagnosis of DENV
      in clinics and hospitals in developing countries.

PMID- 27030493
TI  - Diagnostic Accuracy of the Small Membrane Filtration Method for Diagnosis of
      Pulmonary Tuberculosis in a High-HIV-Prevalence Setting.
AB  - Sputum acid-fast bacilli (AFB) smear microscopy has suboptimal sensitivity but
      remains the most commonly used laboratory test to diagnose pulmonary tuberculosis
      (TB). We prospectively evaluated the small membrane filtration (SMF) method that
      concentrates AFB in a smaller area to facilitate detection to improve the
      diagnostic performance of microscopy. We enrolled adults with suspicion of
      pulmonary TB from health facilities in southwestern Uganda. Clinical history,
      physical examination, and 3 sputum samples were obtained for direct fluorescent
      AFB smear, SMF, Xpert MTB/RIF, and MGIT culture media. Sensitivity and
      specificity were estimated for SMF, AFB smear, and Xpert MTB/RIF, using MGIT as
      the reference standard. The analysis was stratified according to HIV status. From
      September 2012 to April 2014, 737 participants were included in the HIV-infected
      stratum (146 [20.5%] were culture positive) and 313 were in the HIV-uninfected
      stratum (85 [28%] were culture positive). In HIV-infected patients, the
      sensitivity of a single SMF was 67.4% (95% confidence interval [CI], 59.9% to
      74.1%); for AFB, 68.0% (95% CI, 60.6% to 74.6%); and for Xpert MTB/RIF, 91.0%
      (95% CI, 85.0% to 94.8%). In HIV-uninfected patients, the corresponding
      sensitivities were 72.5% (95% CI, 62.1% to 80.9%), 80.3% (95% CI, 70.8% to
      87.2%), and 93.5% (95% CI, 85.7% to 97.2%). The specificity for all 3 tests in
      both HIV groups was >=96%. In this setting, the SMF method did not improve the
      diagnostic accuracy of sputum AFB. The Xpert MTB/RIF assay performed well in both
      HIV-infected and -uninfected groups.

PMID- 27030494
TI  - [A retrospective analysis on the pernicious placenta previa from 2008 to 2014].
AB  - OBJECTIVE: To investigate the incidence changes, clinical characteristics and
      pregnant outcomes of pernicious placenta previa. METHODS: A retrospective cohort
      analysis on 316 cases with placenta previa in the Peking University First
      Hospital from January 2008 to December 2014. The research group were 60 cases
      with the patients of placenta previa with the history of cesarean section, and
      the control group were placenta previa without the history of cesarean section.
      Compared with the incidence, intraoperative blood loss, the pregnancy outcomes
      and so on. RESULTS: (1) The average incidence rate of placenta previa during the
      past 7 years was 10.96 0/00 (316/28 837). And the cases of pernicious placenta
      previa was 60 (2.080/00, 60/28 837), the incidence of pernicious placenta previa
      was rising from 2008 to 2014 (0.910/00-3.080/00). (2) There were 145 cases of
      placenta privia had been translation from other hospitals in the past 7 years.
      The referral rate of pregnant women with placenta previa was 45.9% (145/316), and
      the referral rate of pernicious placenta previa (63.3%, 38/60) was significantly
      higher than that of non-pernicious placenta previa group (41.8%, 107/256;
      chi(2)=9.080, P=0.003). Referral the outcomes of these patients were good, and no
      maternal death occurred. (3) The placenta in the research group were mainly
      adhered in the front wall of the uterine, and the incidence was 38.5% (15/39),
      higher than that in the group of non-pernicious placenta previa (12.1%, 21/174;
      chi(2)=57.636, P<0.01). The incidence rate of complicated placenta increased in
      research group was 53.3% (32/60), higher than that in the group of non-pernicious
      placenta previa, compared with the control group, there was significant
      difference (15.6%, 40/256; chi(2)= 39.041, P<0.01). (4) The incidence of blood
      loss was more than 1 000 ml, blood transfusion rate, the rate of hysterectomy and
      the rate of asphyxia of newborn in the research group were respectively 41.7%
      (25/60), 38.3% (23/60), 8.3% (5/60), 15.0% (9/60), and the incidence of the group
      of non-pernicious placenta previa were respectively 4.7% (12/256), 12.9%
      (33/256), 1.2% (3/256), 8.6% (22/256), compared those in other two groups, there
      were not significant difference (P<0.05). CONCLUSIONS: The incidence rate of
      placenta previa increased year by year, patients with placenta previa has a
      history of cesarean section often combined with placenta in anterior wall of the
      uterus, and often with poor pregnancy outcomes. Hierarchical referral system is
      an effective means to reduce the mortality of the pernicious placenta previa.

PMID- 27030495
TI  - [Modified Prolift procedure without trachelectomy or hysterectomy for the
      treatment of advanced pelvic organ prolapse complicated with cervical
      elongation].
AB  - OBJECTIVE: To evaluate the effect and safety of a modified Prolift procedure,
      without preceding partial trachelectomy or hysterectomy for pelvic organ prolapse
      (POP) with coexistent cervical elongation. METHODS: Clinical data of 72 patients
      that underwent a modified Prolift procedure for POP with coexistent cervical
      elongation, between December 2008 and June 2012 in Fuzhou General Hospital of
      Nanjing Military Command was retrospectively analysed. A comparison was carried
      out between preoperative and postoperative parameters of pelvic organ prolapse
      quantitation system (POP-Q), and an objective evaluation was made according to
      the overall cure rate and recurrence rate. Pelvic floor distress inventory-short
      form 20 (PFDI-20) was used to investigate the subjective cure rate and
      improvement of symptoms. RESULTS: Patients were followed up at median 52 months
      (36-78 months). One bladder perforation and one rectum perforation occurred
      during the procedure. Four patients (6%, 4/72) had uterine prolapse at 9-19
      months after the opertaion and had transvaginal hysterectomy laterly. The overall
      anatomical correction rate was 94% (68/72). Six patients (8%, 6/72) had mesh
      exposures at 3-9 months after the opertaion. Scores of PFDI-20 decreased
      sifnificantly after the procedure (118.2+/-25.2 vs 12.1+/-8.0 vs 12.5+/-9.5 vs
      13.0+/-9.9, P< 0.05). The patients' satisfaction rate was 92% (66/72).
      CONCLUSION: This modified Prolift procedure, without preceding partial
      trachelectomy or hysterectomy, could effectively and safely correct POP with
      coexistent cervical elongation.

PMID- 27030496
TI  - [Effects of cystectomy for ovary benign cyst on ovarian reserve and pregnancy
      outcome of in vitro fertilization-embryo transfer cycle].
AB  - OBJECTIVE: To investigate the impact of previous cystectomy for ovary benign cyst
      on ovarian reserve and pregnancy outcome in in vitro
      fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)
      cycles. METHODS: Totally 622 infertility patients were retrospectively
      investigated who underwent first IVF/ICSI-ET cycle in Reproductive Hospital
      Affiliated to Shandong University from January 2013 to June 2014. There were 153
      cases who had been removed ovarian cyst by cystectomy surgeries recruited as
      study group, in which 44 cases of ovarian endometriosis cyst, 35 cases of benign
      ovarian teratomas, 67 cases of simple ovarian cyst and 7 cases of ovarian
      mucinous cystadenoma. In contrast, 469 infertility patients with tubal-factor
      infertility or male factor were included as control group. The age-matched women
      in the control group had no ovarian surgery previously. The indicators of ovarian
      reserve and pregnancy outcome were analyzed between two groups. The influence of
      different types of ovarian cysts on ovarian reserve and pregnancy outcome in
      IVF/ICSI-ET cycles were also studied, ovarian endometriosis cyst was studied as
      Group A, and Group B consisted of benign ovarian teratomas, simple ovarian cyst
      and mucinous cystadenoma. RESULTS: (1) The significantly lower serum
      antimullerian hormone (AMH) level (median: 1.92 versus 2.90 mg/L), antral
      follicle count (AFC; median: 12.0 versus 13.0), retrieved oocytes (12+/-5 versus
      13+/-6) and the number of embryo cryopreserved (median: 1.0 versus 3.0) were
      found in study group compared with control group (all P<0.05). There was no
      statistical difference between two group for the following parameters, such as
      basal FSH level, the total dosage of gonadotropin duration and the total dosage
      of gonadotropin (all P>0.05). A better clinical pregnancy rate was achieved in
      control group (61.6%, 241/391) than that in study group (61.4%, 81/132), but no
      significant difference was existed (P=0.96). (2) Compared to Group B, Group A had
      fewer AFC, lower serum AMH level, retrieved oocytes and the number of embryo
      cryopreserved (11+/-4 versus 13+/-5; 1.65 versus 2.15 mg/L; 9+/-4 versus 13+/-5;
      0 versus 2.0; all P< 0.01). There was a lower clinical pregnancy rate in Group A
      than that in Group B [50.0% (19/38) versus 66.0% (62/94)], accompanying with
      higher abortion rate [3/19 versus 9.7% (6/62)], but no differences were observed
      (all P>0.05). CONCLUSIONS: Ovarian reserve declines after the cystectomy for
      ovarian benign cysts and the cystectomy has a negative impact on IVF/ICSI-ET
      cycle, resulting in a decrease of the number of retrieved oocytes and the number
      of embryo cryopreserved, but do not influence clinical pregnancy outcome. Ovarian
      reserve is impaired more seriously by cystectomy for ovarian endometriosis cyst
      than other ovarian benign cyst.

PMID- 27030497
TI  - [Diagnosis and treatment value of colposcopy and loop electrosurgical excision
      procedure in microinvasive cervical cancer: analysis of 135 cases].
AB  - OBJECTIVE: To explore the sensitivity and specificity of colposcopy directed
      biopsy (CDB) and the value of loop electrosurgical excision procedure (LEEP) for
      the diagnosis and treatment of microinvasive cervical cancer (MCC). METHODS: One
      hundred and thirty five patients with MCC were diagnosed with LEEP in Obstetrics
      and Gynecology Hospital, Fudan University from April 2008 to November 2010, and
      were retrospectively analyzed on CDB diagnoses and following treatment after
      LEEP. According to patient's desire for preservation of fertility and cone margin
      status, following strategies after LEEP included follow-up, second LEEP,
      hysterectomy, modified radical hysterectomy and radical hysterectomy. Single and
      multiple factors related to residual lesions after LEEP were analysed with
      Pearson Chi-square test and logistic regression model, respectively. RESULTS: CDB
      diagnosed MCC with a sensitivity of 4.4 % (6/135), specificity of 100.0% (4 680/4
      680), and false negative rate of 95.6% (129/135). Among the 135 patients, 29 did
      not receive further treatment in our hospital and lost contact. One hundred and
      six patients had secondary treatment or follow-up in our hospital, 4 of among
      which were closely followed up; one hundred and two received further treatment,
      which included 6 cases with second LEEP (3 received extrafascial hysterectomy
      after repeat LEEP), 59 cases hysterectomy, 14 cases modified radical hysterectomy
      and 26 cases radical hysterectomy. For factors related to residual lesions after
      LEEP, single factor analysis showed that the ratio of residual lesion in patients
      aged 27-39, 40-49 and 50-65 years were respectively 19.0% (11/58), 15.4% (10/65)
      and 5/12 (chi(2)=4.505, P=0.105). Residual lesions occurred in 24.7% (23/93) of
      patients with positive LEEP margins, which was more than that 7.1% (3/42) of
      patients with negative LEEP margins (chi(2)=5.756, P=0.016). The ratio of
      residual lesions in patients with positive endocervical, ectocervical and deep
      stromal margins were respectively 29.6%(8/27), 17.1%(7/41) and 30.6%(11/36;
      chi(2)= 2.275, P=0.321). Residual lesions in patients with or without lymph
      vascular space invasion (LVSI) were 2/7 and 18.8% (24/128), respectively
      (chi(2)=0.412, P=0.521). The ratio of residual lesions in patients with invasion
      depth of <1 mm was 17.1% (7/41), 1-<3 mm was 19.0% (16/84), and 3-5 mm was 3/10,
      with no significant difference among three groups (chi(2)=0.870, P=0.647).
      Logistic regression analysis showed positive cone margin (OR=5.069, P=0.014) and
      age (OR=1.080, P=0.024) were the independent risk factors of residual lesions
      after LEEP conization. CONCLUSIONS: CDB alone is not adequate for the diagnosis
      of MCC. For young patients who desire to preserve fertility with a negative cone
      margin, close follow-up is acceptable. Cone margin status and age are two
      independent risk factors for residual lesions after LEEP.

PMID- 27030498
TI  - [Expression and clinical significance of ELOVL6 gene in high-grade serous ovarian
      carcinoma].
AB  - OBJECTIVE: To investigate the expression of elongation of very long-chain fatty
      acids family member 6 (ELOVL6) in high-grade serous ovarian carcinoma (HSOC), and
      explore the correlation between its expression and clinical prognosis in these
      patients. METHODS: The expression of ELOVL6 at mRNA and protein levels were
      respectively detected by reverse transcription (RT)-PCR and immune histochemistry
      method in 12 cases with normal ovarian tissues and 172 cases with HSOC from
      primary tumor site, forty of which had paired peritoneal metastatic tissues.
      RESULTS: (1) The results tested by RT-PCR showed that ELOVL6 expression in normal
      ovarian tissue was 4.8+/-1.1, while 1.2+/-0.7 in primary tumors and 1.8+/-0.9
      peritoneal metastatic sites in HSOC. Compared with normal ovarian tissue, the
      level of ELOVL6 mRNA was significantly lower in HSOC (P<0.05). There was no
      significant difference between primary and peritoneal metastatic sites in HSOC
      (P=0.610). It was shown that ELOVL6 protein localized in cytoplasm of ovarian
      cancer cell by immunostaining assay. (2) ELOVL6 expression was observed in all
      normal ovarian tissue, 70.2% of G1-G2 and 48.8% of G3 HSOC (P<0.05). ELOVL6
      expression in drug-resistant group were significantly lower than that in non
      resistant group (39.1% vs 65.0%, P<0.01). The median disease-free survival was 41
      months in the ELOVL6-positive group and 39 months in ELOVL6-negative group
      (P>0.05). The total median survival was 52 months in ELOVL6-positive group and 44
      months in ELOVL6-negative group (P>0.05). CONCLUSION: Low expression of ELOVL6
      may correlate with the poor differentiation and drug resistance in HSOC.

PMID- 27030499
TI  - [Effectiveness research of medicated gamma intrauterine device and medicated
      genefix intrauterine device inserted immediately after abortion].
AB  - OBJECTIVE: To compare the effectiveness of medicated gamma intrauterine device
      (IUD) and medicated genefix IUD inserted immediately after abortion. METHODS: A
      multicenter clinical trail was performed for the study from Mar. 2012 to Jan.
      2013. Totally 840 women who volunteered to participate were randomly allocated to
      gamma-group (medicated gamma IUD) or genefix-group (medicated genefix IUD)
      immediately after abortion. While 464 abortion women who had not used IUD or
      steroids contraceptive methods were chosen as control group. The effectiveness of
      the IUD were followed up for 1 year. All women were required to record the number
      of vaginal bleeding days and blood volume of vaginal bleeding within 3 months
      after abortion. RESULTS: At the 12(th) month, the expulsion was the most common
      reason for termination. The expulsion rates of genefix-group and gamma-group were
      2.48/100 women years and 3.12/100 women years, respectively (P>0.05). For the
      expulsion reasons, IUD moving down could account for more than seventy percent.
      The removal rate for IUD usage of two IUD groups were almost equal (3.91/100
      women years verus 4.35/100 women years), the differences were not statistically
      significant (P>0.05). At the 90(th) day after abortion, comparing with control
      group, the bleeding and (or) spotting days of genefix-group and gamma-group
      extended by 3.9 and 2.6 days respectively, the differences had statistical
      significance between the three groups (P<0.05). Among the bleeding and (or)
      spotting days, spotting days prolonged significantly. At the 12(t)h month,
      spotting days of genefix-group and gamma-group were (9.2+/-5.9) days and (8.5+/
      4.6) days respectively, more than (5.2+/-4.0) days of control group. The
      differences had statistical significance between IUD with control group (P<0.05),
      and had not between the two kinds of IUD (P>0.05). CONCLUSION: The insertion of
      medicated genefix IUD and medicated gamma IUD immediately after abortion is safe,
      feasible, has slight side effects and could be effective contraception.

PMID- 27030500
TI  - [Adiponectin exerts antiproliferative effect on high glucose-induced BeWo cell
      proliferation in vitro].
AB  - OBJECTIVE: To determine the effects of adiponectin on high glucose induced BeWo
      cell proliferation in vitro. METHODS: BeWo cells were seeded in 96-well plates at
      the appropriate density. After treatments with high glucose (25 mmol/L), western
      blot analysis of cyclin D1 and a colorimetric assay (cell counting kit-8, CCK-8)
      were used to analyse BeWo cells' proliferation, and western blot was used to
      detect the expression of adiponectin. Moreover, we added adiponectin (20 MUg/ml)
      in the culture medium and three methods were utilized for cell proliferation
      analysis: CCK-8, cell cycle analysis (by flow cytometry) and proliferating cell
      nuclear antigen (PCNA) immunocytochemical staining. RESULTS: Compared to BeWo
      cells cultured by normal glucose and high mannitol, the proliferation of BeWo
      cells treated by high glucose increased (P<0.05). Compared with BeWo cells
      cultured by high mannitol, the expression of adiponectin in BeWo cells treated by
      high glucose decreased. After added adiponectin in the culture medium, the
      proliferation of BeWo cells treated by adiponectin+high glucose decreased than
      that of cells treated by high glucose (0.770+/-0.050 versus 0.990+/-0.070,
      P<0.05); the proportion of G2+S phases of BeWo cells treated by adiponectin+high
      glucose decreased than that of cells treated by high glucose [(40.7+/-2.1)%
      versus (44.9+/- 3.9)%, P<0.05]; the rate of PCNA positive cell in BeWo cells
      treated by adiponectin+high glucose decreased than that of cells treated by high
      glucose [(28+/-5)% versus (44+/-5)%, P<0.05]. CONCLUSION: Adiponectin could
      inhibit proliferation of high glucose induced BeWo cells in vitro.

PMID- 27030501
TI  - [Impact of biological function on ovarian clear cell carcinoma ES2 cell line with
      ARID1A gene expression down-regulating in vitro].
AB  - OBJECTIVE: To investigate the efficiency of biological function of AT rich
      interaction domain 1A (ARID1A) gene silenced by small interfering RNA (siRNA) on
      ovarian clear cell carcinoma ES2 cell line. METHODS: (1) The three pairs ARID1A
      gene siRNA interference fragments siN1 (ARID1A-705), siN2 (ARID1A-1513), siN3
      (ARID1A-2282) and one pair negative control were respectively designed, and
      transfected into ES2 cells by RNA interference max reagent transiently. Reverse
      transcription (RT)-PCR and western blot methods were used to detect the
      expression of ARID1A mRNA and protein in ES2 cells transfected with interference
      fragments respectively. So as to select the best silencing effect of siRNA
      interference fragment(that was siN3), and then was used in the following
      experiment. (2) The following experiment were divided into three groups, namely
      siN3 transfection group, negative control group and blank control group. The
      proliferative activity of three groups of cells after transient transfection (6,
      24, 48, 72, 96 hours) was assessed by cell counting kit-8 (CCK-8) assay and
      expressed as absorbance (A) value; the apoptosis rate of three groups of cells
      transfected transiently with interference fragment was measured by flow cytometry
      with annexin V/propidium iodide (PI) staining; the ability of cellular invasion
      of three groups of cells transfected transiently with interference fragment was
      tested by transwell experiment; the expression of nuclear factor-kappa B (NF
      kappaB), membrane type-1 matrix metalloproteinase (MT1-MMP) and matrix
      metalloproteinase-2 (MMP2) protein in ES2 cells transfected transiently with
      interference fragment was measured by western blot. RESULTS: (1) The RT-PCR
      results showed that the ARID1A mRNA relative expression levels in ES2 cells after
      transfected transiently with siN1, siN2 and siN3 were 0.007 8+/-0.005 7, 0.006
      8+/-0.000 3 and 0.002 8+/-0.000 3 respectively. They were all apparently lower
      than that in the negative control group (0.034 6+/-0.001 3; all P<0.01). The
      western blot results showed that the expression levels of ARID1A protein were
      0.439 4+/-0.000 7, 0.424 4+/-0.005 0 and 0.386 0+/-0.005 8 respectively. They
      were also lower than that in the negative control group (0.732 4 +/-0.030 3; all
      P<0.01). The siN3 with the highest transfection efficiency was selected to use in
      the following experiment. (2) The CCK-8 method showed that the proliferative
      activity of siN3 transfection group cells after transfected transiently at 6
      hours was not statistically significant difference compared with those in
      negative control group and blank control group (0.506+/-0.010, 0.491+/-0.006,
      0.498+/-0.009, respectively; all P>0.05). However, the proliferative activity of
      siN3 transfection group cells after transfected transiently at 24, 48, 72, 96
      hours were higher than those in negative control group and blank control group
      (all P<0.01). The flow cytometry results showed that the apoptosis rate of siN3
      transfection group cells was (20.0+/-3.9)%, which was significantly lower than
      those in negative control group and blank control group [(31.5+/-5.0)%, (34.0+/
      4.2)%, respectively; all P<0.05]. The transwell experiment showed that the
      penetrated cell counts of siN3 transfection group was 60.4+/-2.9, which was
      apparently higher than those in negative control group and blank control group
      (54.2+/-3.5, 52.1+/-3.8, respectively; all P<0.01). Western blot experiment
      showed that the relative expression levels of NF-kappaB, MT1-MMP and MMP2 protein
      in siN3 transfection group were respectively 1.85+/-0.16, 0.37+/-0.08, 1.38+/-
      0.11, which were apparently higher than those in negative control group (0.93+/
      0.11, 0.17+/-0.05, 0.86+/-0.06; all P<0.05) and blank control group (0.94 +/-
      0.04, 0.15 +/- 0.08, 0.85 +/- 0.10, respectively; all P<0.01). CONCLUSIONS: It
      would be to promote the cell doubling time, reduce cell apoptosis and increase
      the invasive capability in ES2 cells that ARID1A expression was down-regulating
      by ARID1A mRNA interference. The invasion mechanism may be related to the
      activation of NF-kappaB signal transduction pathway, up-regulation of MT1-MMP
      expression and then promoting the invasion of tumor cells via the up-regulation
      of MMP2 expression.

PMID- 27030503
TI  - A preliminary ex vivo study of 3D ultrasonography of aortic atherosclerosis using
      autopsied aorta.

PMID- 27030502
TI  - Soleus Hoffmann reflex amplitudes are specifically modulated by cutaneous inputs
      from the arms and opposite leg during walking but not standing.
AB  - Electrical stimulation of cutaneous nerves innervating heteronymous limbs (the
      arms or contralateral leg) modifies the excitability of soleus Hoffmann (H-)
      reflexes. The differences in the sensitivities of the H-reflex pathway to
      cutaneous afferents from different limbs and their modulation during the
      performance of motor tasks (i.e., standing and walking) are not fully understood.
      In the present study, we investigated changes in soleus H-reflex amplitudes
      induced by electrical stimulation of peripheral nerves. Selected targets for
      conditioning stimulation included the superficial peroneal nerve, which
      innervates the foot dorsum in the contralateral ankle (cSP), and the superficial
      radial nerve, which innervates the dorsum of the hand in the ipsilateral (iSR) or
      contralateral wrist (cSR). Stimulation and subsequent reflex assessment took
      place during the standing and early-stance phase of treadmill walking in ten
      healthy subjects. Cutaneous stimulation produced long-latency inhibition
      (conditioning-test interval of ~100 ms) of the H-reflex during the early-stance
      phase of walking, and the inhibition was stronger following cSP stimulation
      compared with iSR or cSR stimulation. In contrast, although similar conditioning
      stimulation significantly facilitated the H-reflex during standing, this effect
      remained constant irrespective of the different conditioning sites. These
      findings suggest that cutaneous inputs from the arms and contralateral leg had
      reversible effects on the H-reflex amplitudes, including inhibitions with
      different sensitivities during the early-stance phase of walking and facilitation
      during standing. Furthermore, the differential sensitivities of the H-reflex
      modulations were expressed only during walking when the locations of the afferent
      inputs were functionally relevant.

PMID- 27030504
TI  - TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol
      for evaluating safety and feasibility of autologous human adult dental pulp stem
      cell therapy in patients with chronic disability after stroke.
AB  - RATIONALE: Stroke represents a significant global disease burden. As of 2015,
      there is no chemical or biological therapy proven to actively enhance
      neurological recovery during the chronic phase post-stroke. Globally, cell-based
      therapy in stroke is at the stage of clinical translation and may improve
      neurological function through various mechanisms such as neural replacement,
      neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity.
      Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke
      as reported in four independent studies indicates improvement in neurobehavioral
      function with adult human dental pulp stem cell therapy. Human adult dental pulp
      stem cells present an exciting potential therapeutic option for improving post
      stroke disability. AIMS: TOOTH (The Open study Of dental pulp stem cell Therapy
      in Humans) will investigate the use of autologous stem cell therapy for stroke
      survivors with chronic disability, with the following objectives: (a) determine
      the maximum tolerable dose of autologous dental pulp stem cell therapy; (b)
      define that dental pulp stem cell therapy at the maximum tolerable dose is safe
      and feasible in chronic stroke; and (c) estimate the parameters of efficacy
      required to design a future Phase 2/3 clinical trial. METHODS AND DESIGN: TOOTH
      is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design
      that comprises three stages: Stage 1 will involve the selection of 27
      participants with middle cerebral artery ischemic stroke and the commencement of
      autologous dental pulp stem cell isolation, growth, and testing in sequential
      cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem
      cell in each cohort of participants with an ascending dose and subsequent
      observation for a 6-month period for any dental pulp stem cell-related adverse
      events. Stage 3 will investigate the neurosurgical intervention of the maximum
      tolerable dose of autologous dental pulp stem cell followed by 9 weeks of
      intensive task-specific rehabilitation. Advanced magnetic resonance and positron
      emission tomography neuro-imaging, and clinical assessment will be employed to
      probe any change afforded by stem cell therapy in combination with
      rehabilitation. SAMPLE SIZE ESTIMATES: Nine participants will step-wise progress
      in Stage 2 to a dose of up to 10 million dental pulp stem cell, employing a
      cumulative 3 + 3 statistical design with low starting stem cell dose and
      subsequent dose escalation, assuming that an acceptable probability of dose
      limiting complications is between 1 in 6 (17%) and 1 in 3 (33%) of patients. In
      Stage 3, another 18 participants will receive an intracranial injection with the
      maximum tolerable dose of dental pulp stem cell. OUTCOMES: The primary outcomes
      to be measured are safety and feasibility of intracranial administration of
      autologous human adult DPSC in patients with chronic stroke and determination of
      the maximum tolerable dose in human subjects. Secondary outcomes include
      estimation of the measures of effectiveness required to design a future Phase 2/3
      clinical trial.

PMID- 27030505
TI  - Experts call for younger men to be offered PSA test for prostate cancer.

PMID- 27030506
TI  - Psychological Resilience.

PMID- 27030507
TI  - BMP4 mediates the interplay between adipogenesis and angiogenesis during
      expansion of subcutaneous white adipose tissue.
AB  - The expansion of subcutaneous (SC) white adipose tissue (WAT) has beneficial
      effects on metabolic health. Our previous work showed an increased number of bone
      morphogenetic protein 4 (BMP4)-activated beige adipocytes in SC WAT, indicating a
      potential role of BMP4 in adipocyte recruitment. It was also demonstrated that
      BMP4 committed multipotent mesodermal C3H10T1/2 stem cells to the adipocyte
      lineage ex vivo However, the mechanism by which BMP4 regulates adipogenesis in
      vivo has not been clarified. In this study, we found that BMP4 stimulated de novo
      adipogenesis in SC WAT concomitant with enhanced blood vessel formation, thus
      promoting adipose tissue angiogenesis. Platelet-derived growth factor receptor
      beta-positive (PDGFRbeta(+)) multipotent stem cells within the neoangiogenic
      vessels were found to be adipocyte progenitors. Moreover, BMP4 downregulated
      PDGFRbeta by stimulating the lysosome-dependent degradation, which efficiently
      initiated adipogenic differentiation. These results suggest how BMP4 regulates
      adipocyte recruitment in SC WAT, and thus promote its beneficial metabolic
      effects.

PMID- 27030508
TI  - Colonic stenting in patients on P2Y12 receptor antagonists and direct oral
      anticoagulants: are current BSG/ESGE guidelines practical?

PMID- 27030509
TI  - Involvement of transient receptor potential A1 channel in algesic and analgesic
      actions of the organic compound limonene.
AB  - BACKGROUND: TRPA1 is a Ca-permeable nonselective cation channel expressed in
      sensory neurons and acts as a nocisensor. Recent reports show that some
      monoterpenes, a group of naturally occurring organic compounds, modulate TRP
      channel activity. Here, we report that limonene, being contained in citrus fruits
      and mushrooms, shows a unique bimodal action on TRPA1 channel. METHODS: We
      examine the effects of limonene on sensory neurons from wild-type, TRPV1- and
      TRPA1-gene-deficient mice and on heterologously expressed channels in vitro.
      Molecular determinants were identified with using mutated channels. Cellular
      excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic
      actions of limonene are also examined in vivo. RESULTS: In wild-type mouse
      sensory neurons, limonene increased the intracellular Ca(2+) concentration
      ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not
      TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive
      ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse.
      Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar
      injection of limonene elicited acute pain, which was significantly less in TRPA1
      (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours
      evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low
      concentration of limonene significantly inhibited H2 O2 -induced TRPA1
      activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive
      cysteine-mutated channels. CONCLUSIONS: Topically applied limonene stimulates
      TRPA1, resulting in elicitation of acute pain, but its systemic application
      inhibits nociception induced by oxidative stress. Because limonene is a safe
      compound, it may be utilized for pain control due to its inhibition of TRPA1
      channels. What does this study add: Limonene, a monoterpene in essential oils of
      various plants, has been known for its antitumor and anti-inflammatory
      properties. However, molecular basis of their actions has not been identified.
      This study shows that limonene activates nociceptive TRPA1 and elicits acute
      pain, when it is topically applied. In addition, systemic application of limonene
      exerts inhibitory effects on nociception induced by an oxidative stress-induced
      TRPA1 activation.

PMID- 27030510
TI  - Altruistic traits are predicted by neural responses to monetary outcomes for self
      vs charity.
AB  - Human altruism is often expressed through charitable donation-supporting a cause
      that benefits others in society, at cost to oneself. The underlying mechanisms of
      this other-regarding behavior remain imperfectly understood. By recording event
      related-potential (ERP) measures of brain activity from human participants during
      a social gambling task, we identified markers of differential responses to
      receipt of monetary outcomes for oneself vs for a charitable cause. We focused
      our ERP analyses on the frontocentral feedback-related negativity (FRN) and three
      subcomponents of the attention-related P300 (P3) brain wave: the frontocentral P2
      and P3a and the parietal P3b. The FRN distinguished between gains and losses for
      both self and charity outcomes. Importantly, this effect of outcome valence was
      greater for self than charity for both groups and was independent of two altruism
      related measures: participants' pre-declared intended donations and the actual
      donations resulting from their choices. In contrast, differences in P3
      subcomponents for outcomes for self vs charity strongly predicted both of our
      laboratory measures of altruism-as well as self-reported engagement in real-life
      altruistic behaviors. These results indicate that individual differences in
      altruism are linked to individual differences in the relative deployment of
      attention (as indexed by the P3) toward outcomes affecting other people.

PMID- 27030511
TI  - Structure Based Docking and Molecular Dynamic Studies of Plasmodial Cysteine
      Proteases against a South African Natural Compound and its Analogs.
AB  - Identification of potential drug targets as well as development of novel
      antimalarial chemotherapies with unique mode of actions due to drug resistance by
      Plasmodium parasites are inevitable. Falcipains (falcipain-2 and falcipain-3) of
      Plasmodium falciparum, which catalyse the haemoglobin degradation process, are
      validated drug targets. Previous attempts to develop peptide based drugs against
      these enzymes have been futile due to the poor pharmacological profiles and
      susceptibility to degradation by host enzymes. This study aimed to identify
      potential non-peptide inhibitors against falcipains and their homologs from other
      Plasmodium species. Structure based virtual docking approach was used to screen a
      small non-peptidic library of natural compounds from South Africa against 11
      proteins. A potential hit, 5alpha-Pregna-1,20-dien-3-one (5PGA), with inhibitory
      activity against plasmodial proteases and selectivity on human cathepsins was
      identified. A 3D similarity search on the ZINC database using 5PGA identified
      five potential hits based on their docking energies. The key interacting residues
      of proteins with compounds were identified via molecular dynamics and free
      binding energy calculations. Overall, this study provides a basis for further
      chemical design for more effective derivatives of these compounds. Interestingly,
      as these compounds have cholesterol-like nuclei, they and their derivatives might
      be well tolerated in humans. 

PMID- 27030512
TI  - Dysregulated 14-3-3 Family in Peripheral Blood Leukocytes of Patients with
      Schizophrenia.
AB  - The 14-3-3 family, which is composed of seven distinct members in humans, plays
      important roles in the cell cycle, apoptosis, synaptic plasticity and neuronal
      differentiation and migration. Previous genetic and post-mortem gene expression
      studies have linked this family to schizophrenia. However, the direction of gene
      expression changes in these studies has been inconsistent, and reports of 14-3-3
      gene expression in living schizophrenic patients are still lacking. Here, we
      assessed 14-3-3 gene and protein expression levels in peripheral blood leukocytes
      from drug-naive first-episode schizophrenic patients and matched controls. mRNA
      and protein expression levels were quantified by qRT-PCR and UPLC-MRM/MS,
      respectively. Expression analysis revealed four downregulated and one upregulated
      mRNA transcripts as well as five downregulated protein levels of 14-3-3 isoforms
      in schizophrenia. Moreover, significant positive correlations between 14-3-3 mRNA
      and protein expression levels were found in schizophrenia, and we also identified
      negative correlations between epsilon, theta and zeta isoform expression levels
      and positive symptoms of schizophrenia. Our results suggest that gene and protein
      expression levels for the 14-3-3 family are dysregulated in schizophrenia,
      perhaps owing to specific regulatory mechanisms, and we also suggest that
      expression of the 14-3-3epsilon, theta and zeta isoform genes could be useful
      indicators of disease severity. 

PMID- 27030513
TI  - Double-stranded RNAs induce a pattern-triggered immune signaling pathway in
      plants.
AB  - Pattern-triggered immunity (PTI) is a plant defense response that relies on the
      perception of conserved microbe- or pathogen-associated molecular patterns (MAMPs
      or PAMPs, respectively). Recently, it has been recognized that PTI restricts
      virus infection in plants; however, the nature of the viral or infection-induced
      PTI elicitors and the underlying signaling pathways are still unknown. As double
      stranded RNAs (dsRNAs) are conserved molecular patterns associated with virus
      replication, we applied dsRNAs or synthetic dsRNA analogs to Arabidopsis thaliana
      and investigated PTI responses. We show that in vitro-generated dsRNAs, dsRNAs
      purified from virus-infected plants and the dsRNA analog polyinosinic
      polycytidylic acid (poly(I:C)) induce typical PTI responses dependent on the co
      receptor SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1 (SERK1), but independent of
      dicer-like (DCL) proteins in Arabidopsis. Moreover, dsRNA treatment of
      Arabidopsis induces SERK1-dependent antiviral resistance. Screening of
      Arabidopsis wild accessions demonstrates natural variability in dsRNA
      sensitivity. Our findings suggest that dsRNAs represent genuine PAMPs in plants,
      which induce a signaling cascade involving SERK1 and a specific dsRNA receptor.
      The dependence of dsRNA-mediated PTI on SERK1, but not on DCLs, implies that
      dsRNA-mediated PTI involves membrane-associated processes and operates
      independently of RNA silencing. dsRNA sensitivity may represent a useful trait to
      increase antiviral resistance in cultivated plants.

PMID- 27030514
TI  - Association between fluid balance and mortality in patients with septic shock: a
      post hoc analysis of the TRISS trial.
AB  - BACKGROUND: Several studies have shown an association between a positive fluid
      balance and increased mortality in patients with septic shock. This may have led
      to a more restrictive use of intravenous fluids. The association between fluid
      accumulation and mortality in the setting of a more restrictive use of
      intravenous fluids, however, is uncertain. We therefore aimed to investigate the
      association between a cumulative fluid balance 3 days after randomization and 90
      day mortality in a recent Nordic multicentre cohort of patients with septic
      shock. METHODS: A post hoc analysis of patients from the Transfusion Requirements
      in Septic Shock (TRISS) trial treated for 3 days or more in the ICU after
      randomization. The patients were categorized into four groups depending on their
      weight-adjusted cumulative fluid balance after 3 days. We performed multivariable
      Cox regression analysis, adjusting for important prognostics (study site, age,
      chronic cardiovascular and chronic lung disease, haematologic malignancy, chronic
      dialysis, source of infection, baseline SOFA score and plasma lactate). RESULTS:
      The median cumulative fluid balance of the 841 included patients was 2480 ml (IQR
      47-5045). The median time from ICU admission to inclusion in the trial was 22 h.
      The overall 90-day mortality was 52%. There was no statistically significant
      association between fluid balance 3 days from inclusion and 90-day mortality
      after the adjustment for the prognostics (P = 0.37). CONCLUSION: In our cohort of
      patients with septic shock and a comparably low cumulative fluid balance, there
      was no association between fluid balance and mortality. However, the study design
      and the limited power preclude strong conclusions. There is an urgent need for
      high-quality trials assessing the benefit and harm of different fluid volume
      strategies in patients with septic shock.

PMID- 27030516
TI  - Revisiting the vortex-core tunnelling spectroscopy in YBa2Cu3O7-delta.
AB  - The observation by scanning tunnelling spectroscopy of Abrikosov vortex cores in
      the high-temperature superconductor YBa2Cu3O7-delta (Y123) has revealed a robust
      pair of electron-hole symmetric states at finite subgap energy. Their
      interpretation remains an open question because theory predicts a different
      signature in the vortex cores, characterized by a strong zero-bias conductance
      peak. Here, we present scanning tunnelling spectroscopy data on very homogeneous
      Y123 at 0.4 K revealing that the subgap features do not belong to vortices: they
      are actually observed everywhere along the surface with high spatial and energy
      reproducibility, even in the absence of magnetic field. Detailed analysis and
      modelling show that these states remain unpaired in the superconducting phase and
      belong to an incoherent channel, which contributes to the tunnelling signal in
      parallel with the superconducting density of states. 

PMID- 27030515
TI  - mTOR Inhibition improves anaemia and reduces organ damage in a murine model of
      sickle cell disease.
AB  - Mechanistic target of rapamycin (mTOR) has been shown to play an important role
      in red blood cell physiology, with inhibition of mTOR signalling leading to
      alterations in erythropoiesis. To determine if mTOR inhibition would improve
      anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual
      mTORC1/2 inhibitor, INK128. One week after daily oral drug treatment, erythrocyte
      count, haemoglobin, and haematocrit were all significantly increased while
      reticulocyte counts were reduced. These parameters remained stable during 3 weeks
      of treatment. Similar effects were observed following oral treatment with the
      mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle
      cell erythrocytes in circulation, reduced spleen size, and reduced renal and
      hepatic iron accumulation in SCD mice. Following middle cerebral artery
      occlusion, stroke size was reduced in SCD mice treated with sirolimus. In
      conclusion, mTOR inhibition is protective against anaemia and organ damage in a
      murine model of SCD.

PMID- 27030517
TI  - Using knowledge as the basis for evidence-based practice in primary care nurses.
AB  - AIM: The aim of this study was to explore the perception of primary care nurses
      regarding the need and use of knowledge from research, as a basis for evidence
      based practice in their workplace. Additionally, the study aimed to determine
      which factors might hinder or enable implementation into daily practice.
      BACKGROUND: Evidence-based practice involves integrating best results in research
      with clinical experience, which enables us to provide a higher quality of care,
      as well as to optimize the care given. International studies show that nurses
      feel that there are still many barriers that hinder their doing research and
      incorporating new findings into clinical practice; although in the field of
      primary care, few studies have been carried out. METHODS: This descriptive
      qualitative study design used focus groups to collect data. This study was
      carried out in Spanish primary care centres. Forty-six registered nurses took
      part in this study and were divided into five focus groups. RESULTS: Three
      significant themes emerged: awareness of the need to use research, nurses as
      knowledge-generation agents and motivation to use research despite barriers.
      LIMITATIONS: A limited number of participants and a convenience sample were used.
      CONCLUSION: Nurses recognize that professional health care must be based on
      evidence obtained from daily work - both originated by their colleagues and by
      themselves - and they are willing to work on it although they perceive a lack of
      competence for this purpose and demand support from their institutions.
      IMPLICATIONS FOR NURSING POLICY: Primary care institutions should empower nursing
      coordinators as leaders of evidence-based practice and implicate clinical nurses
      from the beginning on the implementation of guidelines.

PMID- 27030518
TI  - Prioritization of anticancer drugs against a cancer using genomic features of
      cancer cells: A step towards personalized medicine.
AB  - In this study, we investigated drug profile of 24 anticancer drugs tested against
      a large number of cell lines in order to understand the relation between drug
      resistance and altered genomic features of a cancer cell line. We detected
      frequent mutations, high expression and high copy number variations of certain
      genes in both drug resistant cell lines and sensitive cell lines. It was observed
      that a few drugs, like Panobinostat, are effective against almost all types of
      cell lines, whereas certain drugs are effective against only a limited type of
      cell lines. Tissue-specific preference of drugs was also seen where a drug is
      more effective against cell lines belonging to a specific tissue. Genomic
      features based models have been developed for each anticancer drug and achieved
      average correlation between predicted and actual growth inhibition of cell lines
      in the range of 0.43 to 0.78. We hope, our study will throw light in the field of
      personalized medicine, particularly in designing patient-specific anticancer
      drugs. In order to serve the scientific community, a webserver, CancerDP, has
      been developed for predicting priority/potency of an anticancer drug against a
      cancer cell line using its genomic features
      (http://crdd.osdd.net/raghava/cancerdp/). 

PMID- 27030519
TI  - Electrochemical properties of a thermally expanded magnetic graphene composite
      with a conductive polymer.
AB  - A magnetic graphene composite derived from stage-1 FeCl3-graphite intercalation
      compounds was thermally treated for up to 75 min at 400  degrees C or for 2 min
      at high temperatures up to 900  degrees C. These heat-treatments of the magnetic
      graphene composite gave rise to the cubical expansion of graphene with the
      enlargement of inter-graphene distances. The specific capacitance of the magnetic
      graphene composite increased upon heating and reached 42 F g(-1) at a scan rate
      of 5 mV s(-1) in 1.0 M NaCl, after being treated for 2 min at 900  degrees C.
      This value corresponds to 840% increase in the capacitance activity superior to
      that (5 F g(-1)) of the pristine magnetic graphene composite before heat
      treatment. This capacitance enhancement can play a significant role in the
      increase of the surface area that reached 17.2 m(2) g(-1) during the non
      defective inter-graphene exfoliation. Moreover, the magnetic graphene composite
      heated at 900  degrees C was hybridized with polyaniline by in situ
      polymerization of aniline to reach a specific capacitance of 253 F g(-1) at 5 mV
      s(-1). The current procedure of heat-treatment and hybridization with a
      conductive polymer can be an effective method for attaining a well-expanded
      magnetic graphene composite possessing an enhanced electrochemical activity with
      a relatively high energy density (141 W h kg(-1) in 1.0 M NaCl) and an excellent
      stability (99% after 9000 cycles of 20 A g(-1)).

PMID- 27030520
TI  - Social support as a predictor of diet and exercise self-efficacy in patients with
      coronary artery disease.
AB  - OBJECTIVES: This study examined the role of social support and other factors in
      relation to exercise and diet self-efficacy in Chinese patients with coronary
      heart disease in Hong Kong. METHODS: A cross-sectional study was conducted on a
      convenience sample identified from two cardiac rehabilitation centers. Eighty
      five participants joined the study. RESULTS: Both self-efficacy measures
      correlated with social support, in particular in the domains of
      emotional/informational support and positive social interactions. Stronger social
      support was independently associated with a higher level of exercise and diet
      self-efficacy. Patients with a higher body mass index had a lower level of
      exercise self-efficacy, whereas social drinkers had a lower level of diet self
      efficacy. CONCLUSIONS: Our data supported an association between social support
      and self-efficacy. It was suggested that social companions would help patients
      get greater confidence in overcoming barriers to lifestyle modification. Further
      studies may investigate what type of social support contributes to improving the
      self-efficacy beliefs of patients.

PMID- 27030521
TI  - Improved Ventricular Function after TEE-guided Cardioversion of Atrial
      Arrhythmias in Patients after the Fontan Operation.
AB  - OBJECTIVE: Atrial tachyarrhythmias frequently develop after the Fontan operation.
      Patients with Fontan physiology rely on atrial contribution to cardiac output,
      and thus control of atrial arrhythmias is important. Outcomes after cardioversion
      in patients after Fontan have not been reported. We sought to determine if
      cardioversion results in improved echocardiographic parameters or clinical
      symptomatology; and, discern risk factors for arrhythmia recurrence. DESIGN: We
      retrospectively analyzed the Mayo Clinic echocardiographic database to capture
      patients after the Fontan operation who underwent transesophageal
      echocardiography-guided electrical cardioversion from 2000-2015. Clinical and
      echocardiographic data were collected and compared at baseline and follow-up.
      RESULTS: Eight hundred ninety patients with prior Fontan operation underwent
      echocardiographic evaluation; 341 (38%) developed atrial arrhythmias. Thirty-six
      patients [20 males, median age 29 (12-51)] underwent transesophageal
      echocardiography-guided cardioversion of atrial arrhythmias [atrial
      flutter/intraatrial reentrant tachycardia (75%); atrial fibrillation (25%)]. At
      follow-up, improvements were noted in ejection fraction by 10% (P < .0001);
      atrioventricular valve regurgitation grade (39%) (P = .002); New York Heart
      Association (NYHA) class (61%) (P < .001); and resolution of spontaneous echo
      contrast in the Fontan circuit (65%) (P < .01). No embolic events occurred
      following cardioversion. Eighteen patients (50%) developed recurrent atrial
      arrhythmias at 15 (3-36) months after cardioversion. Five-year freedom from
      arrhythmia recurrence was 61%. Significant univariate predictors of arrhythmia
      recurrence were atrial flutter/intraatrial reentrant tachycardia (HR = 4.3, P =
      .02); NYHA >= II (HR = 4.1, P = .03); systemic right ventricle (HR = 5.2; P =
      .02); and ejection fraction <= 40% (HR = 2.8; P = .04). On multivariate analysis,
      only systemic right ventricle (HR = 3.7; P = .02) remained an independent
      predictor of arrhythmia recurrence. CONCLUSION: After the Fontan operation,
      cardioversion of atrial arrhythmias improves ventricular function,
      atrioventricular valve regurgitation grade, and NYHA class. Arrhythmia recurrence
      was common and patients with atrial flutter/intraatrial reentrant tachycardia,
      systemic right ventricle, or reduced ventricular function may be at risk of
      arrhythmia recurrence. Further studies are required to identify additional risk
      factors and protective factors for arrhythmia recurrence.

PMID- 27030522
TI  - Profiles Using Indicators of Marital Communication, Communication Styles, and
      Marital Satisfaction in Mexican Couples.
AB  - Marital problems have multiple causes. One factor leading to marital
      dissatisfaction is communication, both the inability to communicate in certain
      areas and the way in which communication is made. One hundred four Mexican
      couples who attend a reproductive health care institution in Mexico City took
      part in this study. The relationship between the amount and style of
      communication was studied in order to develop profiles with explanatory
      indicators. A study was carried out with two samples (men and women) that were
      classified in terms of marital satisfaction or dissatisfaction. Indicators
      related to marital satisfaction are talking about the marital relationship,
      discussing work (women and men), communicating about sexuality (women).
      Indicators of marital dissatisfaction are talking about children, having and
      perceiving a reserved and negative style of communication (men), having and
      perceiving a negative and violent style of communication (women).

PMID- 27030523
TI  - Pd(0)-catalyzed cross-coupling of allyl halides with alpha-diazocarbonyl
      compounds or N-mesylhydrazones: synthesis of 1,3-diene compounds.
AB  - With palladium catalysis, allyl bromides or chlorides react with alpha
      diazocarbonyl compounds or N-mesylhydrazones to afford 1,3-diene derivatives. The
      reaction represents a novel and efficient method for the synthesis of 1,3
      butadiene derivatives. Mechanistically, the reaction is proposed to follow a
      pathway involving the formation of a pi-allylic palladium carbene complex and
      subsequent migratory insertion. 

PMID- 27030524
TI  - Pain: SHIP-1 activation for IC/BPS?

PMID- 27030525
TI  - Kidney cancer: No advantage of adjuvant sunitinib or sorafenib.

PMID- 27030527
TI  - Stones: The dark side of stone disease - stones do still kill.

PMID- 27030528
TI  - Kidney cancer: Recurrence in renal cell carcinoma: the work is not done.

PMID- 27030529
TI  - Histidine-rich glycoprotein derived peptides affect endometrial angiogenesis in
      vitro but has no effect on embryo development.
AB  - Histidine-rich glycoprotein (HRG) is an abundant plasma protein involved in
      multiple biological processes including immunology, vascularisation, and
      coagulation. These processes are of importance in regulating embryo development
      and implantation. A specific polymorphism in the HRG gene, HRG C633T, has an
      impact on various aspects of fertility, such as oocyte quality, endometrial
      receptivity, and possibly the capacity of the embryo itself to implant. To
      further examine the potential role of the HRG C633T polymorphism in regulating
      endometrial angiogenesis and on embryo development, two HRG peptides were
      constructed. These HRG peptides correspond to the amino acids 169-203 of the
      protein which, in turn, reflects the C633T polymorphism in the gene. The HRG
      proline or serine peptides were added to cultures of primary human endometrial
      endothelial (HEE) cells and to human embryos in vitro. The HRG peptides inhibited
      vascular endothelial growth factor (VEGF) induced proliferation and migration and
      promoted tube formation of HEE cells. The embryos were monitored using a time
      lapse system (EmbryoScope(r)). Except for a prolonged time from first cleavage
      after thawing to development of the morula, no difference in embryo
      morphokinetics or embryo quality was noted in human embryos cultured in the
      presence of the HRG proline peptide. Taken together, these results suggest that
      treatment with a specific HRG peptide might prime the endometrium for
      implantation and be beneficial for adequate placentation. However, addition of a
      specific HRG proline peptide to human embryos has no beneficial effects in terms
      of embryo development. ABBREVIATIONS: HRG: histidine-rich glycoprotein; HEE:
      human endometrial endothelial; VEGF: vascular endothelial growth factor; TSP:
      thrombospondin; SNP; single nucleotide polymorphism; IVF: in vitro fertilization;
      CLESH-1: CD36 LIMPII Emp structural homology domain-1; ECM: endothelial cell
      medium; FBS: fetal bovine serum; cDNA: complementary DNA.

PMID- 27030526
TI  - Management of neurogenic bladder in patients with multiple sclerosis.
AB  - Lower urinary tract (LUT) dysfunction is common in patients with multiple
      sclerosis and is a major negative influence on the quality of life of these
      patients. The most commonly reported symptoms are those of the storage phase, of
      which detrusor overactivity is the most frequently reported urodynamic
      abnormality. The clinical evaluation of patients' LUT symptoms should include a
      bladder diary, uroflowmetry followed by measurement of post-void residual urine
      volume, urinalysis, ultrasonography, assessment of renal function, quality-of
      life assessments and sometimes urodynamic investigations and/or cystoscopy. The
      management of these patients requires a multidisciplinary approach. Intermittent
      self-catheterization is the preferred option for management of incomplete bladder
      emptying and urinary retention. Antimuscarinics are the first-line treatment for
      patients with storage symptoms. If antimuscarinics are ineffective, or poorly
      tolerated, a range of other approaches, such as intradetrusor botulinum toxin A
      injections, tibial nerve stimulation and sacral neuromodulation are available,
      with varying levels of evidence in patients with multiple sclerosis. Surgical
      procedures should be performed only after careful selection of patients. Stress
      urinary incontinence owing to sphincter deficiency remains a therapeutic
      challenge, and is only managed surgically if conservative measures have failed.
      Multiple sclerosis has a progressive course, therefore, patients' LUT symptoms
      require regular, long-term follow-up monitoring.

PMID- 27030530
TI  - A novel ammonia-oxidizing archaeon from wastewater treatment plant: Its
      enrichment, physiological and genomic characteristics.
AB  - Ammonia-oxidizing archaea (AOA) are recently found to participate in the ammonia
      removal processes in wastewater treatment plants (WWTPs), similar to their
      bacterial counterparts. However, due to lack of cultivated AOA strains from
      WWTPs, their functions and contributions in these systems remain unclear. Here we
      report a novel AOA strain SAT1 enriched from activated sludge, with its
      physiological and genomic characteristics investigated. The maximal 16S rRNA gene
      similarity between SAT1 and other reported AOA strain is 96% (with "Ca.
      Nitrosotenuis chungbukensis"), and it is affiliated with Wastewater Cluster B
      (WWC-B) based on amoA gene phylogeny, a cluster within group I.1a and specific
      for activated sludge. Our strain is autotrophic, mesophilic (25  degrees C-33 
      degrees C) and neutrophilic (pH 5.0-7.0). Its genome size is 1.62 Mb, with a
      large fragment inversion (accounted for 68% genomic size) inside. The strain
      could not utilize urea due to truncation of the urea transporter gene. The lack
      of the pathways to synthesize usual compatible solutes makes it intolerant to
      high salinity (>0.03%), but could adapt to low salinity (0.005%) environments.
      This adaptation, together with possibly enhanced cell-biofilm attachment ability,
      makes it suitable for WWTPs environment. We propose the name "Candidatus
      Nitrosotenuis cloacae" for the strain SAT1. 

PMID- 27030531
TI  - Effects of dietary pulse consumption on body weight: a systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Obesity is a risk factor for developing several diseases, and
      although dietary pulses (nonoil seeds of legumes such as beans, lentils,
      chickpeas, and dry peas) are well positioned to aid in weight control, the
      effects of dietary pulses on weight loss are unclear. OBJECTIVE: We summarized
      and quantified the effects of dietary pulse consumption on body weight, waist
      circumference, and body fat by conducting a systematic review and meta-analysis
      of randomized controlled trials. DESIGN: We searched the databases MEDLINE,
      Embase, CINAHL, and the Cochrane Library through 11 May 2015 for randomized
      controlled trials of >=3 wk of duration that compared the effects of diets
      containing whole dietary pulses with those of comparator diets without a dietary
      pulse intervention. Study quality was assessed by means of the Heyland
      Methodologic Quality Score, and risk of bias was assessed with the Cochrane Risk
      of Bias tool. Data were pooled with the use of generic inverse-variance random
      effects models. RESULTS: Findings from 21 trials (n = 940 participants) were
      included in the meta-analysis. The pooled analysis showed an overall significant
      weight reduction of -0.34 kg (95% CI: -0.63, -0.04 kg; P = 0.03) in diets
      containing dietary pulses (median intake of 132 g/d or ~1 serving/d) compared
      with diets without a dietary pulse intervention over a median duration of 6 wk.
      Significant weight loss was observed in matched negative-energy-balance (weight
      loss) diets (P = 0.02) and in neutral-energy-balance (weight-maintaining) diets
      (P = 0.03), and there was low evidence of between-study heterogeneity. Findings
      from 6 included trials also suggested that dietary pulse consumption may reduce
      body fat percentage. CONCLUSIONS: The inclusion of dietary pulses in a diet may
      be a beneficial weight-loss strategy because it leads to a modest weight-loss
      effect even when diets are not intended to be calorically restricted. Future
      studies are needed to determine the effects of dietary pulses on long-term weight
      loss sustainability. This protocol was registered at clinicaltrials.gov as
      NCT01594567.

PMID- 27030532
TI  - Outcome of home parenteral nutrition in 251 children over a 14-y period: report
      of a single center.
AB  - BACKGROUND: Parenteral nutrition (PN) is the main treatment for intestinal
      failure. OBJECTIVE: We aimed to review the indications for home parenteral
      nutrition (HPN) in children and describe the outcome over a 14-y period from a
      single center. DESIGN: We conducted a retrospective study that included all
      children who were referred to our institution and discharged while receiving HPN
      between 1 January 2000 and 31 December 2013. The indications for HPN were divided
      into primary digestive diseases (PDDs) and primary nondigestive diseases (PNDDs).
      We compared our results to a previous study that was performed in our unit from
      1980 to 2000 and included 302 patients. RESULTS: A total of 251 patients were
      included: 217 (86%) had a PDD. The mean +/- SD age at HPN onset was 0.7 +/- 0.3
      y, with a mean duration of 1.9 +/- 0.4 y. The indications for HPN were short
      bowel syndrome (SBS) (59%), PNDD (14%), congenital enteropathies (10%), chronic
      intestinal pseudo-obstruction syndromes (9%), inflammatory bowel diseases (5%),
      and other digestive diseases (3%). By 31 December 2013, 52% of children were
      weaned off of HPN, 9% of the PDD subgroup had intestinal transplantation, and 10%
      died mostly because of immune deficiency. The major complications of HPN were
      catheter-related bloodstream infections (CRBSIs) (1.7/1000 d of PN) and
      intestinal failure-associated liver disease (IFALD) (51 children; 20% of cohort).
      An increased rate of CRBSIs was observed compared with our previous study, but we
      saw a decreasing trend since 2012. No noteworthy deceleration of growth was
      observed in SBS children 6 mo after weaning off HPN. CONCLUSIONS: SBS was the
      major indication for HPN in our cohort. IFALD and CRBSIs were potentially life
      threatening problems. Nevertheless, complication rates were low, and deaths
      resulted mostly from the underlying disease.

PMID- 27030533
TI  - DHA supplementation during pregnancy does not reduce BMI or body fat mass in
      children: follow-up of the DHA to Optimize Mother Infant Outcome randomized
      controlled trial.
AB  - BACKGROUND: The omega-3 (n-3) long-chain polyunsaturated fatty acid (LCPUFA)
      docosahexaenoic acid (DHA) has proven effective at reducing fat storage in animal
      studies. However, a systematic review of human trials showed a lack of quality
      data to support or refute this hypothesis. OBJECTIVE: We sought to determine
      whether maternal DHA supplementation during the second half of pregnancy results
      in a lower body mass index (BMI) and percentage of body fat in children. DESIGN:
      We conducted a follow-up at 3 and 5 y of age of children who were born to mothers
      enrolled in the DOMInO (DHA to Optimize Mother Infant Outcome) double-blind,
      randomized controlled trial, in which women with a singleton pregnancy were
      provided with DHA-rich fish-oil capsules (800 mg DHA/d) or vegetable-oil capsules
      (control group) in the second half of pregnancy. Primary outcomes were the BMI z
      score and percentage of body fat at 3 and 5 y of age. Potential interactions
      between prenatal DHA and the peroxisome proliferator-activated receptor-gamma
      (PPARgamma) genotype as a measure of the genetic predisposition to obesity were
      investigated. RESULTS: A total of 1614 children were eligible for the follow-up.
      Parent or caregiver consent was obtained for 1531 children (95%), and these
      children were included in the analysis. BMI z scores and percentages of body fat
      of children in the DHA group did not differ from those of children in the control
      group at either 3 y of age [BMI z score adjusted mean difference: 0.03 (95% CI: 
      0.07, 0.13; P = 0.61); percentage of body fat adjusted mean difference: -0.26
      (95% CI: -0.99, 0.46; P = 0.47)] or 5 y of age [BMI z score adjusted mean
      difference: 0.02 (95% CI: -0.08, 0.12; P = 0.66); percentage of body fat adjusted
      mean difference: 0.11 (95% CI: -0.60, 0.82; P = 0.75)]. No treatment effects were
      modified by the PPARgamma genotype of the child. CONCLUSION: Independent of a
      genetic predisposition to obesity, maternal intake of DHA-rich fish oil during
      the second half of pregnancy does not affect the growth or body composition of
      children at 3 or 5 y of age. This trial was registered at www.anzctr.org.au as
      ACTRN1260500056906 and ACTRN12611001127998.

PMID- 27030534
TI  - Diet low in advanced glycation end products increases insulin sensitivity in
      healthy overweight individuals: a double-blind, randomized, crossover trial.
AB  - BACKGROUND: The consumption of advanced glycation end products (AGEs) has
      increased because of modern food processing and has been linked to the
      development of type 2 diabetes in rodents. OBJECTIVE: We determined whether
      changing dietary AGE intake could modulate insulin sensitivity and secretion in
      healthy, overweight individuals. DESIGN: We performed a double-blind, randomized,
      crossover trial of diets in 20 participants [6 women and 14 men; mean +/- SD body
      mass index (in kg/m(2)): 29.8 +/- 3.7]. Isoenergetic- and macronutrient-matched
      diets that were high or low in AGE content were alternately consumed for 2 wk and
      separated by a 4-wk washout period. At the beginning and end of each dietary
      period, a hyperinsulinemic-euglycemic clamp and an intravenous glucose tolerance
      test were performed. Dietary, plasma and urinary AGEs N(?)-(carboxymethyl)lysine
      (CML), N(?)-(carboxyethyl)lysin (CEL), and methylglyoxal-derived
      hydroimadazolidine (MG-H1) were measured with the use of mass spectrometry.
      RESULTS: Participants consumed less CML, CEL, and MG-H1 during the low-AGE
      dietary period than during the high-AGE period (all P < 0.05), which was
      confirmed by changes in urinary AGE excretion. There was an overall difference in
      insulin sensitivity of -2.1 mg . kg(-1) . min(-1) between diets (P = 0.001).
      Insulin sensitivity increased by 1.3 mg . kg(-1) . min(-1) after the low-AGE diet
      (P = 0.004), whereas it showed a tendency to decrease by 0.8 mg . kg(-1) . min(
      1) after the high-AGE diet (P = 0.086). There was no difference in body weight or
      insulin secretion between diets (P = NS). CONCLUSIONS: A diet that is low in AGEs
      may reduce the risk of type 2 diabetes by increasing insulin sensitivity. Hence,
      a restriction in dietary AGE content may be an effective strategy to decrease
      diabetes and cardiovascular disease risks in overweight individuals. This trial
      was registered at clinicaltrials.gov as NCT00422253.

PMID- 27030535
TI  - Universal equation for estimating ideal body weight and body weight at any BMI.
AB  - BACKGROUND: Ideal body weight (IBW) equations and body mass index (BMI) ranges
      have both been used to delineate healthy or normal weight ranges, although these
      2 different approaches are at odds with each other. In particular, past IBW
      equations are misaligned with BMI values, and unlike BMI, the equations have
      failed to recognize that there is a range of ideal or target body weights.
      OBJECTIVE: For the first time, to our knowledge, we merged the concepts of a
      linear IBW equation and of defining target body weights in terms of BMI. DESIGN:
      With the use of calculus and approximations, we derived an easy-to-use linear
      equation that clinicians can use to calculate both IBW and body weight at any
      target BMI value. We measured the empirical accuracy of the equation with the use
      of NHANES data and performed a comparative analysis with past IBW equations.
      RESULTS: Our linear equation allowed us to calculate body weights for any BMI and
      height with a mean empirical accuracy of 0.5-0.7% on the basis of NHANES data.
      Moreover, we showed that our body weight equation directly aligns with BMI values
      for both men and women, which avoids the overestimation and underestimation
      problems at the upper and lower ends of the height spectrum that have plagued
      past IBW equations. CONCLUSIONS: Our linear equation increases the sophistication
      of IBW equations by replacing them with a single universal equation that
      calculates both IBW and body weight at any target BMI and height. Therefore, our
      equation is compatible with BMI and can be applied with the use of mental math or
      a calculator without the need for an app, which makes it a useful tool for both
      health practitioners and the general public.

PMID- 27030536
TI  - Glyphosate and aminomethylphosphonic acid are not detectable in human milk.
AB  - BACKGROUND: Although animal studies have shown that exposure to glyphosate (a
      commonly used herbicide) does not result in glyphosate bioaccumulation in
      tissues, to our knowledge there are no published data on whether it is detectable
      in human milk and therefore consumed by breastfed infants. OBJECTIVE: We sought
      to determine whether glyphosate and its metabolite aminomethylphosphonic acid
      (AMPA) could be detected in milk and urine produced by lactating women and, if
      so, to quantify typical consumption by breastfed infants. DESIGN: We collected
      milk (n = 41) and urine (n = 40) samples from healthy lactating women living in
      and around Moscow, Idaho and Pullman, Washington. Milk and urine samples were
      analyzed for glyphosate and AMPA with the use of highly sensitive liquid
      chromatography-tandem mass spectrometry methods validated for and optimized to
      each sample matrix. RESULTS: Our milk assay, which was sensitive down to 1 MUg/L
      for both analytes, detected neither glyphosate nor AMPA in any milk sample. Mean
      +/- SD glyphosate and AMPA concentrations in urine were 0.28 +/- 0.38 and 0.30 +/
      0.33 MUg/L, respectively. Because of the complex nature of milk matrixes, these
      samples required more dilution before analysis than did urine, thus decreasing
      the sensitivity of the assay in milk compared with urine. No difference was found
      in urine glyphosate and AMPA concentrations between subjects consuming organic
      compared with conventionally grown foods or between women living on or near a
      farm/ranch and those living in an urban or suburban nonfarming area. CONCLUSIONS:
      Our data provide evidence that glyphosate and AMPA are not detectable in milk
      produced by women living in this region of the US Pacific Northwest. By
      extension, our results therefore suggest that dietary glyphosate exposure is not
      a health concern for breastfed infants. This study was registered at
      clinicaltrials.gov as NCT02670278.

PMID- 27030537
TI  - Molecular Physiology of Membrane Guanylyl Cyclase Receptors.
AB  - cGMP controls many cellular functions ranging from growth, viability, and
      differentiation to contractility, secretion, and ion transport. The mammalian
      genome encodes seven transmembrane guanylyl cyclases (GCs), GC-A to GC-G, which
      mainly modulate submembrane cGMP microdomains. These GCs share a unique topology
      comprising an extracellular domain, a short transmembrane region, and an
      intracellular COOH-terminal catalytic (cGMP synthesizing) region. GC-A mediates
      the endocrine effects of atrial and B-type natriuretic peptides regulating
      arterial blood pressure/volume and energy balance. GC-B is activated by C-type
      natriuretic peptide, stimulating endochondral ossification in autocrine way. GC-C
      mediates the paracrine effects of guanylins on intestinal ion transport and
      epithelial turnover. GC-E and GC-F are expressed in photoreceptor cells of the
      retina, and their activation by intracellular Ca(2+)-regulated proteins is
      essential for vision. Finally, in the rodent system two olfactorial GCs, GC-D and
      GC-G, are activated by low concentrations of CO2and by peptidergic (guanylins)
      and nonpeptidergic odorants as well as by coolness, which has implications for
      social behaviors. In the past years advances in human and mouse genetics as well
      as the development of sensitive biosensors monitoring the spatiotemporal dynamics
      of cGMP in living cells have provided novel relevant information about this
      receptor family. This increased our understanding of the mechanisms of signal
      transduction, regulation, and (dys)function of the membrane GCs, clarified their
      relevance for genetic and acquired diseases and, importantly, has revealed novel
      targets for therapies. The present review aims to illustrate these different
      features of membrane GCs and the main open questions in this field. 

PMID- 27030538
TI  - Celebrate 100: Centenarian secrets to success in business and life, by Steve
      Franklin and Lynn Peters Adler.

PMID- 27030539
TI  - The transfer of titanium dioxide nanoparticles from the host plant to butterfly
      larvae through a food chain.
AB  - This study aimed to examine the transfer of nanoparticles within a terrestrial
      food chain. Oviposited eggs of the swallowtail butterfly (Atrophaneura alcinous)
      were hatched on the leaves of the host plant (Aristolochia debilis), and the root
      stock and root hairs were submerged in a suspension of 10 MUg/ml titanium dioxide
      nanoparticles (TiO2-NPs) in a 100 ml bottle. The presence of TiO2-NPs in the
      veins of the leaves was confirmed by X-ray analytical microscopy (X-ray AM). The
      hatched 1st instar larvae fed on the leaves to moult into 2nd instar larvae.
      Small agglomerates of TiO2-NPs less than 150 nm in diameter were identified in
      the vascular tissue of the exposed plant, the midgut and the excreta of the
      larvae by transmission electron microscopy. The image of Ti elemental mapping by
      X-ray AM was analysed with the quantitative spatial information mapping (QSIM)
      technique. The results demonstrated that TiO2-NPs were transferred from the plant
      to the larvae and they were disseminated throughout the environment via larval
      excreta. 

PMID- 27030540
TI  - Prospective evaluation of treatment regimens, efficacy and safety of a
      recombinant factor VIII concentrate in haemophilia A: the German EffeKt study.
AB  - INTRODUCTION: Collecting clinical data under routine conditions remains important
      to monitor continuously efficacy and tolerability of an established product. AIM:
      This prospective observational study aimed at evaluating efficacy and
      tolerability of full-length sucrose-formulated recombinant FVIII (rFVIII-FS;
      KOGENATE((r)) Bayer/KOGENATE((r)) FS) in routine use and analysing concomitant
      diseases and medication. METHODS: Haemophilia A patients treated with rFVIII-FS
      were followed up for 24 or 36 months. Efficacy, tolerability, concomitant
      medication and diseases were assessed at yearly intervals. RESULTS: Two hundred
      and twenty-one documented patients were mainly pretreated, predominantly with
      prophylaxis (74%). On study, 54 (31%) patients in the efficacy set (n = 174)
      documented regular prophylaxis, 91 patients (52.3%) failed to document their
      prescribed prophylactic infusions, 25 (14.4%) received on-demand treatment and
      four patients (2%) inhibitor adapted therapy. Patients on regular prophylaxis
      reported 8.4% of infusions for bleeding treatment and on-demand patients reported
      55.3%. Young patients experienced mainly trauma-related bleedings and older
      patients reported spontaneous bleedings. Joint status was good overall. Median
      annual spontaneous joint bleeding rate in all groups was zero. A total of 79.0%
      of all bleedings were successfully treated with one or two infusions.
      Degenerative arthropathy and arterial hypertension were the most prominent
      concomitant diseases. Eighty-seven patients (40.5%) took at least one concomitant
      drug on study, mostly drugs for pain treatment related to haemophilic
      arthropathy. Two patients presented with positive inhibitor titres on study, one
      of them was a previously untreated patient and the other had a positive inhibitor
      history. CONCLUSION: This study corroborates the tolerability and efficacy
      profile of rFVIII-FS.

PMID- 27030541
TI  - Iron deficiency and risk of early readmission following a hospitalization for
      acute heart failure.
AB  - AIMS: Early rehospitalization after an episode of acute heart failure (AHF)
      remains excessively high and its prediction a contemporary challenge. Iron
      deficiency (ID) is a frequent finding in AHF, but its prognostic implications
      remain unclear. We sought to evaluate the association between ID and risk of 30
      day readmission in an unselected cohort of patients discharged for AHF. METHODS
      AND RESULTS: Serum ferritin and transferrin saturation (TSAT) were measured
      before discharge in 626 consecutive patients with AHF in a single teaching
      centre. ID was defined as serum ferritin <100 ug/L (absolute ID) or ferritin 100
      299 ug/L with a TSAT <20% (functional ID). Cox regression adapted for competing
      events was used to determine the association between ID and the risk of 30-day
      readmissions. Mean age was 73.4 +/- 10.4 years, 48% were females, and 52.1%
      showed an LVEF >50%. ID was identified in 463 patients (74%): 302 (48.2%) as
      absolute ID and 161 (25.7%) as functional ID. At 30-day post-discharge, 20 (3.2%)
      patients died and 103 (16.5%) were readmitted. Patients with absolute ID showed
      an increased rate of readmission compared with those with functional ID and no ID
      (19.9, 13, and 13.5%, respectively, P = 0.005). In a multivariate setting,
      absolute ID remained associated with higher risk of readmission [hazard ratio
      (HR) 1.72; 95% confidence interval (CI) 1.13-2.60, P = 0.011]. Compared with
      patients without ID, functional ID was not related to the risk of readmission (HR
      0.87; 95% CI 0.46-1.62, P = 0.652). CONCLUSION: In patients with AHF, absolute
      ID, but not functional ID, was associated with an increased risk of early
      readmission.

PMID- 27030542
TI  - Transplantation of Defined Populations of Differentiated Human Neural Stem Cell
      Progeny.
AB  - Many neurological injuries are likely too extensive for the limited repair
      capacity of endogenous neural stem cells (NSCs). An alternative is to isolate
      NSCs from a donor, and expand them in vitro as transplantation material. Numerous
      groups have already transplanted neural stem and precursor cells. A caveat to
      this approach is the undefined phenotypic distribution of the donor cells, which
      has three principle drawbacks: (1) Stem-like cells retain the capacity to
      proliferate in vivo. (2) There is little control over the cells' terminal
      differentiation, e.g., a graft intended to replace neurons might choose a
      predominantly glial fate. (3) There is limited ability of researchers to alter
      the combination of cell types in pursuit of a precise treatment. We demonstrate a
      procedure for differentiating human neural precursor cells (hNPCs) in vitro,
      followed by isolation of the neuronal progeny. We transplanted undifferentiated
      hNPCs or a defined concentration of hNPC-derived neurons into mice, then compared
      these two groups with regard to their survival, proliferation and phenotypic
      fate. We present evidence suggesting that in vitro-differentiated-and-purified
      neurons survive as well in vivo as their undifferentiated progenitors, and
      undergo less proliferation and less astrocytic differentiation. We also describe
      techniques for optimizing low-temperature cell preservation and portability. 

PMID- 27030544
TI  - An epilogue to the review series on modern statistical methods in respiratory
      medicine.

PMID- 27030543
TI  - The topical penta-peptide Gly-Pro-Ile-Gly-Ser increases the proportion of thick
      hair in Japanese men with androgenetic alopecia.
AB  - BACKGROUND: A penta-peptide, Gly-Pro-Ile-Gly-Ser (GPIGS), promotes proliferation
      of mouse hair keratinocytes and accelerates hair growth in mice. AIM OF THIS
      STUDY: This study focused on the ability of the peptide to promote human hair
      growth. METHODS: We used a human hair keratinocyte proliferation assay and organ
      cultures of human hair follicle as in vitro systems. The lotions with and without
      the penta-peptide were administered to 22 Japanese men with androgenetic alopecia
      (AGA) for 4 months in a double-blind and randomized clinical study. RESULTS: The
      penta-peptide significantly stimulated the proliferation of human hair
      keratinocytes at a concentration of 2.3 MUm (P < 0.01), and 5.0 MUm of this
      peptide had a marked effect on hair shaft elongation in the organ culture (P <
      0.05). The change in the proportion of thick hair (>=60 MUm) compared to baseline
      in patients that received the peptide was significantly higher than in the
      placebo (P = 0.006). The change in the proportion of vellus hair (<40 MUm) was
      also significantly lower in the peptide group than in the placebo (P = 0.029).
      The penta-peptide also significantly improved the appearance of baldness (P =
      0.020) when blinded reviewers graded photographs of the participants according to
      a standardized baldness scale. No adverse dermatological effects due to treatment
      were noted during this clinical study. CONCLUSIONS: This penta-peptide promotes
      proliferation of human hair keratinocytes and hair shaft elongation of human hair
      follicles, in vitro. This peptide increases thick hair ratio in vivo, and this
      compound is useful for the improvement of AGA.

PMID- 27030545
TI  - A characterization of verb use in Turkish agrammatic narrative speech.
AB  - This study investigates the characteristics of narrative-speech production and
      the use of verbs in Turkish agrammatic speakers (n = 10) compared to non-brain
      damaged controls (n = 10). To elicit narrative-speech samples, personal
      interviews and storytelling tasks were conducted. Turkish has a large and regular
      verb inflection paradigm where verbs are inflected for evidentiality (i.e. direct
      versus indirect evidence available to the speaker). Particularly, we explored the
      general characteristics of the speech samples (e.g. utterance length) and the
      uses of lexical, finite and non-finite verbs and direct and indirect evidentials.
      The results show that speech rate is slow, verbs per utterance are lower than
      normal and the verb diversity is reduced in the agrammatic speakers. Verb
      inflection is relatively intact; however, a trade-off pattern between inflection
      for direct evidentials and verb diversity is found. The implications of the data
      are discussed in connection with narrative-speech production studies on other
      languages.

PMID- 27030547
TI  - NHS is unprepared for risks posed by climate change, warn leading UK health
      bodies.

PMID- 27030546
TI  - PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation
      via UBE2I inhibition in NB4 cells.
AB  - Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia
      (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated
      sumoylation. PCGF2, a Polycomb group protein, has been suggested as an anti-SUMO
      E3 protein by inhibiting the sumoylation of UBE2I substrates, HSF2 and RANGAP1,
      via direct interaction. Thus, we hypothesized that PCGF2 might play a role in ATO
      induced PML-RARA degradation by interacting with UBE2I. PCGF2 protein was down
      regulated upon ATO treatment in human APL cell line, NB4. Knockdown of PCGF2 in
      NB4 cells, in the absence of ATO treatment, was sufficient to induce sumoylation
      , ubiquitylation- and PML nuclear body-mediated degradation of PML-RARA protein.
      Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic
      and endogenous PML-RARA in 293T and NB4 cells, respectively. In 293T cells, UBE2I
      mediated PML-RARA degradation was reduced upon PCGF2 co-expression. In addition,
      UBE2I-mediated sumoylation of PML-RARA was reduced upon PCGF2 co-expression and
      PCGF2-UBE2I interaction was confirmed by co-immunoprecipitation. Likewise,
      endogenous PCGF2-UBE2I interaction was detected by co-immunoprecipitation and
      immunofluorescence assays in NB4 cells. Intriguingly, upon ATO-treatment, such
      interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized
      with its SUMO substrate, PML-RARA. Taken together, our results suggested a novel
      role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a
      negative regulator of UBE2I via direct interaction. 

PMID- 27030548
TI  - Evaluating Simulation in Training for Arthroscopic Knee Surgery: A Systematic
      Review of the Literature.
AB  - PURPOSE: To evaluate the reported outcomes for measuring the effectiveness of
      simulation during knee arthroscopy training and determine the consistency of
      reporting and validation of simulation used in knee arthroscopy training.
      METHODS: Four databases (MEDLINE, Embase, CINAHL, and Cochrane Central Register
      of Controlled Trials) were screened for studies involving knee arthroscopy
      simulation training. Inclusion and exclusion criteria were applied to the
      searched studies, and a quality assessment was completed for included studies.
      The reviewers searched the references list in each of the eligible studies to
      identify other relevant studies that was not captured by our search strategy.
      RESULTS: We identified 13 eligible studies. The mean number of participants per
      study was 24 (range: 9 to 42 participants). The 3 most commonly reported surgical
      skills were the mean time to perform the task (100%), the visualization and
      probing tasks (77%), and the number of cartilage collisions with measurement of
      the surgical force (46%). The most commonly described measurement instruments
      included the Simulation Built-In Scoring System (54%), motion analysis system
      (23%), and Basic Arthroscopic Knee Skill Scoring System global rating scale
      (15%). The most frequently reported type of validity for the simulator was
      construct validity (54%) and concurrent validity (31%). Moreover, construct
      validity (69%) and concurrent validity (54%) were the most commonly reported type
      of validity for the measurement instrument. CONCLUSIONS: There is significant
      variation in reported learning outcomes and measurement instruments for
      evaluating the effectiveness of knee arthroscopic simulation-based education.
      Despite this, time to perform a task was the most commonly reported skill
      evaluating outcome of simulation. The included studies in this review were of
      variable strength in terms of their evidence and methodologic quality. This study
      highlights the need for consistent outcome reporting after arthroscopic
      simulation training. LEVEL OF EVIDENCE: Level IV, systematic review of Level I,
      II, and IV studies.

PMID- 27030549
TI  - The advantage of laser-capture microdissection over whole tissue analysis in
      proteomic profiling studies.
AB  - Laser-capture microdissection (LCM) offers a reliable cell population enrichment
      tool and has been successfully coupled to MS analysis. Despite this, most
      proteomic studies employ whole tissue lysate (WTL) analysis in the discovery of
      disease biomarkers and in profiling analyses. Furthermore, the influence of
      tissue heterogeneity in WTL analysis, nor its impact in biomarker discovery
      studies have been completely elucidated. In order to address this, we compared
      previously obtained high resolution MS data from a cohort of 38 breast cancer
      tissues, of which both LCM enriched tumor epithelial cells and WTL samples were
      analyzed. Label-free quantification (LFQ) analysis through MaxQuant software
      showed a significantly higher number of identified and quantified proteins in LCM
      enriched samples (3404) compared to WTLs (2837). Furthermore, WTL samples
      displayed a higher amount of missing data compared to LCM both at peptide and
      protein levels (p-value < 0.001). 2D analysis on co-expressed proteins revealed
      discrepant expression of immune system and lipid metabolisms related proteins
      between LCM and WTL samples. We hereby show that LCM better dissected the biology
      of breast tumor epithelial cells, possibly due to lower interference from
      surrounding tissues and highly abundant proteins. All data have been deposited in
      the ProteomeXchange with the dataset identifier PXD002381
      (http://proteomecentral.proteomexchange.org/dataset/PXD002381).

PMID- 27030550
TI  - Kinetics for Zinc Ion Induced Sepia Pharaonis Arginine Kinase Inactivation and
      Aggregation.
AB  - Arginine kinase is an essential enzyme which is closely related to energy
      metabolism in marine invertebrates. Arginine kinase provides a significant role
      in quick response to environmental change and stress. In this study, we simulated
      a tertiary structure of Sepia pharaonis arginine kinase (SPAK) based on the gene
      sequence and conducted the molecular dynamics simulations between SPAK and
      Zn(2+). Using these results, the Zn(2+) binding sites were predicted and the
      initial effect of Zn(2+) on the SPAK structure was elucidated. Subsequently, the
      experimental kinetic results were compared with the simulation results. Zn(2+)
      markedly inhibited the activity of SPAK in a manner of non-competitive
      inhibitions for both arginine and ATP. We also found that Zn(2+) binding to SPAK
      resulted in tertiary conformational change accompanying with the hydrophobic
      residues exposure. These changes caused SPAK aggregation directly. We screened
      two protectants, glycine and proline, which effectively prevented SPAK
      aggregation and recovered the structure and activity. Overall, our study
      suggested the inhibitory effect of Zn(2+) on SPAK and Zn(2+) can trigger SPAK
      aggregation after exposing large extent of hydrophobic surface. The protective
      effects of glycine and proline against Zn(2+) on SPAK folding were also
      demonstrated. 

PMID- 27030551
TI  - Dissecting the Role of K61/K59 Residue in VPS4 Functions.
AB  - ESCRTs (Endosomal Sorting Complexes Required for Transport) are required for the
      formation of the intraluminal vesicles in the multivesicular bodies and are
      involved in other topologically similar processes such as cytokinesis, nuclear
      envelope sealing and viral egress. The final complex ESCRT-III is disassembled by
      the recruitment and activation of the AAA-ATPase VPS4 to the endosomal membranes.
      This recruitment is due to the binding of VPS4 N-terminal MIT with MIM1 and MIM2
      domains present in the CHMPs proteins. By analyzing different cellular membrane
      remodeling events in which VPS4 is involved, here we provide evidence that the
      K61 residue, mapping within the MIT domain of VPS4B (K59 in VPS4A), is involved
      in VPS4 functioning. Posttranslational modifications of this residue might
      modulate MIT-MIM2 binding affinity and, as a consequence, VPS4 functions. 

PMID- 27030553
TI  - N-TERMINALLY ELONGATED SpliInx2 AND SpliInx3 REDUCE BACULOVIRUS-TRIGGERED
      APOPTOSIS VIA HEMICHANNEL CLOSURE.
AB  - The hemichannel and gap junction channel are major portals for the release of
      factors responsible for the effects of apoptotic cells on the spread of apoptosis
      to neighboring cells and apoptotic corpse clearance, typically by phagocytes. The
      N-terminal cytoplasmic domain in the connexins, gap junction proteins in
      vertebrate, has been implicated in regulating channel closure. However, little is
      known about how the hemichannel close responds to apoptotic signaling
      transduction leading to the reduction of neighboring cellular apoptosis in an
      invertebrate. An insect Bac-to-Bac expression system, pFastBac(TM) HT A, allows
      us to construct an N-terminally elongated SpliInx2 (Nte-Inx2) and SpliInx3 (Nte
      Inx3). Here, we demonstrated that recombinant baculovirus Bac-Nte-Inx2 (reBac-Net
      Inx2) and Bac-Nte-Inx3 (reBac-Nte-Inx3) closed the endogenous hemichannel on the
      Sf9 cell surface. Importantly, primary baculovirus infections significantly
      caused early apoptosis, and this apoptosis was reduced by hemichannel-closed Sf9
      cells at 24-h post-infection (PI). Although N-terminal-elongated residue led to
      the increase in the phosphorylated sites in both Nte-Inx2 and Nte-Inx3 and an
      additional transmembrane domain in Nte-Inx3, both the proteins localized on the
      cell surface, suggesting Nte-Inxs proteins could mediate hemichannel closure.
      Further supporting evidence showed that hemichannel closure was dependent on N
      Inxs expressed by baculovirus polyhedrin promoter, which began to express at 18
      24 h PI. These results identify an unconventional function of N-terminal
      elongated innexins that could act as a plug to manipulate hemichannel closure and
      provide a mechanism connecting the effect of hemichannel closure directly to
      apoptotic signaling transduction from intracellular to extracellular compartment.

PMID- 27030554
TI  - One-step microwave synthesized core-shell structured selenium@carbon spheres as
      cathode materials for rechargeable lithium batteries.
AB  - A core-shell structured selenium@carbon composite material was obtained by a
      facile one-step microwave synthesis method. The uniform carbon shells coated on
      selenium spheres greatly minimized the shuttle effect of Li-Se cells. The
      morphology analysis of the cathodes after different cycles revealed that the Se
      cores were perfectly confined inside the unbroken C shells all through the 100
      cycles. 

PMID- 27030556
TI  - The European Society of Peadiatric Radiology : Search for a new European Managing
      Editor.

PMID- 27030552
TI  - Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant
      Intracellular Pathogen.
AB  - Chlamydia species infect millions of individuals worldwide and are important
      etiological agents of sexually transmitted disease, infertility, and blinding
      trachoma. Historically, the genetic intractability of this intracellular pathogen
      has hindered the molecular dissection of virulence factors contributing to its
      pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions
      on the use of antibiotics as selectable markers have impeded the development of
      molecular tools to genetically manipulate these pathogens. However, recent
      developments in the field have resulted in significant gains in our ability to
      alter the genome of Chlamydia, which will expedite the elucidation of virulence
      mechanisms. In this review, we discuss the challenges affecting the development
      of molecular genetic tools for Chlamydia and the work that laid the foundation
      for recent advancements in the genetic analysis of this recalcitrant pathogen. 

PMID- 27030557
TI  - Reminder letters for bowel screening tests improve uptake.

PMID- 27030558
TI  - Molecular interaction studies of green tea catechins as multitarget drug
      candidates for the treatment of Parkinson's disease: computational and structural
      insights.
AB  - Green tea catechins have extensively been studied for their imminent role in
      reducing the risk of various neurodegenerative diseases such as Parkinson's
      disease (PD). Understanding the molecular interaction of these compounds with
      various anti-Parkinsonian drug targets is of interest. The present study is
      intended to explore binding modes of catechins with molecular targets having
      potential role in PD. Lamarckian genetic algorithm methodology was adopted for
      molecular docking simulations employing AutoDock 4.2 program. Toxicity potential
      and molecular properties responsible for good pharmacokinetic profile were
      calculated by Osiris property explorer and Molinspiration online toolkit,
      respectively. A strong correlation coefficient (r(2) = 0.893) was obtained
      between experimentally reported and docking predicted activities of native co
      crystallized ligands of the 18 target receptors used in current study. Analysis
      of docked conformations revealed monoamine oxidase-B as most promising, while N
      methyl-D-aspartate receptor was recognized as the least favorable target for
      catechins. Benzopyran skeleton with a phenyl group substituted at the 2-position
      and a hydroxyl (or ester) function at the 3-position has been identified as
      common structural requirements at majority of the targets. The present findings
      suggest that epigallocatechin gallate is the most promising lead to be developed
      as multitarget drug for the design and development of novel anti-Parkinsonian
      agents. 

PMID- 27030559
TI  - Organizational uncertainty and stress among teachers in Hong Kong: work
      characteristics and organizational justice.
AB  - A growing literature now exists examining the relationship between organizational
      justice and employees' experience of stress. Despite the growth in this field of
      enquiry, there remain continued gaps in knowledge. In particular, the
      contribution of perceptions of justice to employees' stress within an
      organizational context of uncertainty and change, and in relation to the new and
      emerging concept of procedural-voice justice. The aim of the current study was to
      examine the main, interaction and additive effects of work characteristics and
      organizational justice perceptions to employees' experience of stress (as
      measured by their feelings of helplessness and perceived coping) during an
      acknowledged period of organizational uncertainty. Questionnaires were
      distributed among teachers in seven public primary schools in Hong Kong that were
      under threat of closure (n = 212). Work characteristics were measured using the
      demand-control-support model. Hierarchical regression analyses observed
      perceptions of job demands and procedural-voice justice to predict both teachers'
      feelings of helplessness and perceived coping ability. Furthermore, teacher's
      perceived coping was predicted by job control and a significant interaction
      between procedural-voice justice and distributive justice. The addition of
      organizational justice variables did account for unique variance, but only in
      relation to the measure of perceived coping. The study concludes that in addition
      to 'traditional' work characteristics, health promotion strategies should also
      address perceptions of organizational justice during times of organizational
      uncertainty; and, in particular, the value and importance of enhancing employee's
      perceived 'voice' in influencing and shaping justice-related decisions.

PMID- 27030560
TI  - Reparameterizations of the chi Torsion and Lennard-Jones sigma Parameters Improve
      the Conformational Characteristics of Modified Uridines.
AB  - The currently available force field parameters for modified RNA residues in AMBER
      show significant deviations in conformational properties from experimental
      observations. The examination of the transferability of the recently revised
      torsion parameters revealed that there was an overall improvement in the
      conformational properties for some of the modifications but the improvements were
      still insufficient in describing the sugar pucker preferences (J. Chem. Inf.
      MODEL: 2014, 54, 1129-1142). Here, we report an approach for the development and
      fine tuning of the AMBER force field parameters for 2-thiouridine, 4-thiouridine,
      and pseudouridine with diverse conformational preferences. The chi torsion
      parameters were reparameterized at the individual nucleoside level. The effect of
      combining the revised gamma torsion parameter and modifying the Lennard-Jones
      sigma parameters were also tested by directly comparing the conformational
      preferences obtained from our extensive molecular dynamics simulations with those
      from experimental observations. (c) 2016 Wiley Periodicals, Inc.

PMID- 27030561
TI  - [The depressive disorders during the early rehabilitation period following
      preceding ischemic stroke: the possibilities for the application of the enhanced
      external counterpulsation method].
AB  - The authors present arguments in favour of the necessity to reveal and treat the
      co-morbid conditions with special reference to depressive disorders in the
      patients during the early rehabilitation period following preceding ischemic
      stroke. They demonstrate the importance of the application of non-medicamentous
      therapy in combination with the standard medicamental treatment. Special emphasis
      is placed on the analysis of the data obtained during evaluation of the
      effectiveness of combined therapy with the use of the enhanced external
      counterpulsation method in the early post-stroke period. It is concluded that the
      early diagnostics and timely correction of anxio-depressive conditions promotes
      the efficiency of rehabilitative measures and improves the quality of life of the
      patients with such disorders. 

PMID- 27030562
TI  - [Restoration of the complicated locomotor functions of the upper extremities in
      the patients surviving ischemic stroke].
AB  - During the late and residual periods of stroke, it is necessary to pay attention
      to the training of complex spatial movements along with the traditional
      restoration of the balance and strength of para-articular muscles and the
      mobility of the paretic limb joints. The objective of the present study was to
      evaluate the effectiveness of robotic therapy for the recovery of the functions
      of the upper extremities in the late and residual periods of stroke. The study
      involved 52 patients who had survived ischemic stroke in the middle cerebral
      artery. The patients were divided randomly into 2 groups. All of them performed
      therapeutic physical exercises based on the standard technique during 5 days a
      week for 3 weeks. In addition, the treatment included massage, laser and pulsed
      current therapy. The patients of the main group (n=36) were additionally trained
      to perform complex spatial movements with special emphasis on their speed,
      fluidity, precision, and agility with the use of the Multi Joint System (MJS)
      robotic electromechanical device (40 min, 5 days/wk x 3wk). The analysis of the
      results of the study has demonstrated the statistically significant difference in
      the degree of improvement of the range of motion (ROM) in the elbow and shoulder
      joints, the speed and the accuracy of these movements between the patients of the
      main and control groups. It is concluded that the instrumental restoration of
      complex spatial movements of the upper extremities during the late and residual
      periods of stroke contributes not only to the improvement of the functional
      capabilities but also to the enhancement of independence and personal adjustment
      of the stroke patients. 

PMID- 27030563
TI  - [On the importance of the reflectory-segmental effects for the combined treatment
      of knee joint osteoporosis in the patients of advanced age].
AB  - The present article demonstrates the role of reflectory-segmental effects during
      baro-laser therapy for the treatment of arthrosis of the knee joints in elderly
      patients. It has been shown that the additional treatment of the lumbosacral
      region while applying baro-laser therapy in the patients of the advanced age
      significantly enhances their functional capabilities including the increase of
      duration of painless walking and the reduced intensity of the pain syndrome. 

PMID- 27030564
TI  - [The adaptive changes of homeostasis under the influence of high-intensity
      physical exercises].
AB  - The present article was designed to report the results of the investigation into
      various non-specific adaptive reactions of the organism (NARO) based on the
      determination of the ratio of lymphocyte to neutrophil levels in the blood of the
      athletes under conditions of high-intensity training. We evaluated the frequency
      of different types of adaptive responses in the biathlon skiers at different
      stages of their annual training cycle. The study has demonstrated the
      relationship between metabolic changes under the influence of training and the
      type of adaptive responses. It is concluded that the adaptive stress responses
      are associated with the increased "metabolic cost" paid for the performance of
      strenuous exercises which can be a cause of slowdown of the adaptive processes
      and lead to overtraining. 

PMID- 27030565
TI  - [The topical problems of physical health of the children and adolescents].
AB  - The objective of the present study was to evaluate the level of the physical
      development and health of the children and adolescents depending on the age and
      sex using the methods and principles of pathophysiological investigations. The
      study involved 15,067 Moscow-based schoolchildren at the age varying from 7 to 17
      years, including 7,760 boys and 7,307 girls. It was shown that the girls aged 7
      14 and boys 8-16 years had body mass index (BMI) significantly different from the
      respective normal-for-age values. The boys aged 8 years or more had a
      significantly higher BMI than the girls of the same age which suggests a greater
      prevalence of the hypersthenic body type among the boys of this age group. The
      most intensive growth of body mass index was observed in both the girls and the
      boys during the period between 8 and 9 years. It is concluded that BMI in
      addition to gender and age is a major factor influencing the health status of the
      schoolchildren. The children and adolescents having the normal body type were
      characterized by a higher physical health index (PHI) in comparison to those with
      hypo- or hypersthenic body type. The index of physical health sharply decreased
      in both the boys and the girls within the first school year. A rise in the index
      of physical health was observed in the girls starting from the age of 14 years
      and in the boys from the age of 13 years. By the age of 17 years, the boys had a
      higher index of physical health in comparison with that in the girls. By the time
      of graduation from school, the index of physical health was lower regardless of
      gender than it was at the entry to school. 

PMID- 27030566
TI  - [The comprehensive pathogenetic approach to the neuro-orthopedic rehabilitation
      of the children of different age presenting with cerebral palsy].
AB  - OBJECTIVES: The present study was aimed at the improvement of comprehensive neuro
      orthopedic rehabilitation of the children of different age presenting with
      cerebral palsy. MATERIAL AND METHODS: A total of 267 patients with infantile
      cerebral paralysis at the age from 1 year to 16 years were available for the
      observation including 158 (59.2%) boys and 109 (40.8%) girls. RESULTS: The
      orthopedic treatment of locomotor disorders was adjusted for the patients' age,
      the neuropsychiatric status, and the type of autonomous dysfunction. The
      conservative treatment was given 104 (39%) patients and the surgical intervention
      performed on 163 (61%) ones. Vegetative disbalance was the predominant condition
      in the children aged up to 3 years. Orthopedic alignment of the muscle tone was
      one of the most common methods of the treatment. We used milestone plaster
      bandages for immobilization followed by wearing the orthoses and orthopedic shoes
      in combination with massage and therapeutic physical exercises. The surgical
      treatment aimed at the normalization of the musculo-ligamentous apparatus was the
      predominant strategy for the age group of 4-7 years. The conservative treatment
      was most frequently prescribed for the correction of vegetative dystonia. The
      physiotherapeutic methods were applied differentially. In the groups of children
      aged from 8 to 12 years and from 13 to 15 years, the surgical correction was
      aimed at the elimination of gross deformities. The differentiated treatment and
      the use of different types of equipment proved highly efficient for the
      elimination of muscle spasticity and hypotrophy as well as for the correction of
      corporal deformities. Moreover, it helped to restore and improve the motor
      ability. The children's physical development and mental capacity have also been
      stimulated.

PMID- 27030567
TI  - [The formation of the self-maintenance skills in the pre-school children
      presenting with locomotor and coordination disorders].
AB  - The Ministry of Health of the Russian Federation acknowledges the sharp rise in
      the prevalence of congenital malformation in this country during the past 30
      years. In 2010-2011, this pathology was estimated to occur in 3% of the children.
      It includes a variety of locomotor and coordination disorders of which the most
      widespread are infantile cerebral paralysis, ataxia, consequences of perinatal
      lesions of the central nervous system, etc. This article contains a detailed
      description of these locomotor and coordination disorders. AIM: The objective of
      the present work was to elaborate and evaluate the program for the formation of
      the self-maintenance skills in the pre-school children presenting with locomotor
      and coordination disorders under conditions of family guidance and education.
      PATIENTS AND METHODS: The study was carried out from September 2013 till May 2014
      based at MUP DOD "Semeiny klub Nadezhda" ("The Hope Family Club", Municipal
      unitary facility for children's additional education) and supported by B.N.
      El'tsin Ural Federal University. It included 10 children suffering from locomotor
      and coordination disorders of different severity and members of their families.
      The following methods were used: the self-service skills scorecard , monitoring
      formation of the motor skills, and Wilcoxon's T-test. RESULTS: The use of the
      program based on the cooperation with the children's families allowed to achieve
      positive dynamics in the patients' conditions. Moreover, 30% of them acquired the
      full scope of the self-maintenance skills. The most pronounced changes in the
      motor abilities were apparent in the movements of the upper and lower extremitis,
      walking, and motion in space. CONCLUSION: The proposed program for the formation
      of the self-maintenance skills in the pre-school children presenting with
      locomotor and coordination disorders proved to be highly efficacious. The study
      has demonstrated the importance of the parents' involvement in the process of
      formation of the self-maintenance skills and motor abilities. It is concluded
      that the formation of the self-maintenance skills and locomotor abilities are two
      interdependent processes.

PMID- 27030568
TI  - [The topical problems of pediatric balneotherapy and the spa and health resort
      based treatment of the children].
AB  - This article is devoted to the topical problems of pediatric balneotherapy with
      special reference to the organization of the spa and health resort-based
      treatment of the children in the Russian Federation. The main issues discussed by
      the authors include the current state of health resort care for the children, the
      problem of statutory regulation of the activities of the children's spa and
      health resort facilities, the approaches to increasing the availability of the
      spa and health resort-based treatment for the children at the enhanced risk of
      the development of chronic diseases, disabilities, and tuberculosis. Also
      considered are the problems of the development of the regulatory framework for
      the medical rehabilitation of the children based at the spa and health resort
      facilities. The principal goals to be sought in climatotherapy, physiotherapy,
      balneotherapy, and pelotherapy in the pediatric context are outlined along with
      the further prospects for the development of the main areas of pediatric
      balneology. 

PMID- 27030569
TI  - [The development of the medical information system for the improvement of the
      quality of work of the Crimean spa and health resorts].
AB  - The Crimea has the enormous potential for the health promotion activities.
      However, neither the profile of these activities nor the demand for the socio
      medical services is clearly defined for the majority of the local spa and health
      resort facilities. The possibilities of modern information technology are not
      used in the full measure either. The objective of the present work was to
      elaborate the new medical information system and demonstrate its effectiveness.
      In addition, the article describes the main advantages of the system for the
      optimization of healthcare in the Crimean spa and health resort facilities. We
      reviewed and analyzed various literature publications, legal framework,
      standards, regulations, guidelines, and questionnaire survey data obtain at 50
      spa and health resort facilities of the Crimea. The results of the assessment
      indicate the necessity of the systematic approach to the analysis of the quality
      of medical care and the process of its further development. Statistical and
      mathematical methods were used to elaborate the medical information system for
      the optimization of the activities of the Crimean spa and health resorts. The
      distinctive features of the proposed information system are modularity and the
      possibility of flexible adjustment to the conditions of individual settings, one
      step data loading with the subsequent multiple application for the formulation of
      documents, automated filling of records in compliance with the medical standards,
      and taking into consideration the possible changes in or amendments to the form
      of the documents. The data obtained in the course of project implementation were
      used for the first time in the Republic of Crimea to design, substantiate, and
      recommend for the practical application the algorithm for the comprehensive
      estimation of the results of treatment of the patients based at the spa and
      health resort facilities with due regard for the specific regional conditions. 

PMID- 27030570
TI  - Recombination spot identification Based on gapped k-mers.
AB  - Recombination is crucial for biological evolution, which provides many new
      combinations of genetic diversity. Accurate identification of recombination spots
      is useful for DNA function study. To improve the prediction accuracy, researchers
      have proposed several computational methods for recombination spot
      identification. The k-mer feature is one of the most useful features for modeling
      the properties and function of DNA sequences. However, it suffers from the
      inherent limitation. If the value of word length k is large, the occurrences of k
      mers are closed to a binary variable, with a few k-mers present once and most k
      mers are absent. This usually causes the sparse problem and reduces the
      classification accuracy. To solve this problem, we add gaps into k-mer and
      introduce a new feature called gapped k-mer (GKM) for identification of
      recombination spots. By using this feature, we present a new predictor called SVM
      GKM, which combines the gapped k-mers and Support Vector Machine (SVM) for
      recombination spot identification. Experimental results on a widely used
      benchmark dataset show that SVM-GKM outperforms other highly related predictors.
      Therefore, SVM-GKM would be a powerful predictor for computational genomics.

PMID- 27030571
TI  - Sensory stimulation for persons with dementia: a review of the literature.
AB  - AIMS AND OBJECTIVES: To provide an overview of available sensory stimulation
      interventions, and their effect on persons with dementia and to present
      theoretical and methodological characteristics of the studies included.
      BACKGROUND: Different sensory stimulation interventions are used for persons with
      dementia to increase alertness, reduce agitation and improve quality of life.
      However, the effect of these interventions is not clear, neither are their
      characteristics. DESIGN: A systematic search and review of the literature with
      description of the content and an evaluation of theoretical and methodological
      approaches. METHODS: Systematic searches in CINAHL, PubMed (Medline), The
      Cochrane library and PsycINFO. Studies included have been subject to quality
      assessment by means of Critical Appraisal Skills Programme. RESULTS: Fifty-five
      studies were included and thirty of these documented significant effect. The
      effect of the sensory stimulation interventions mainly reported on negative
      behaviours, except from five studies assessing quality of life and well-being.
      The majority of the studies had methodological limitations. The different sensory
      stimulation interventions were organised into eight categories: music, light
      therapy, acupressure/reflexology, massage/aromatherapy and doll therapy/pet
      therapy/toy therapy, the Sonas programme and Snoezelen. CONCLUSIONS: More studies
      are needed to clarify appropriate substantial background for the specific
      interventions. However, most of the studies based their interventions on a
      theoretical foundation. Furthermore, more research is needed to measure the
      effect of sensory stimulation on communication as well as quality of life. In
      addition, studies are to focus on whether the effect depends on the stage of
      dementia. RELEVANCE TO CLINICAL PRACTICE: Nurses are to be aware of sensory
      stimulation as a possible intervention to improve persons' quality of life.

PMID- 27030572
TI  - High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice
      with CFA-induced knee arthritis.
AB  - OBJECTIVE: Our aim was to quantify nociceptive spontaneous behaviors, knee edema,
      proinflammatory cytokines, bone density, and microarchitecture in high-fat diet
      (HFD)-fed mice with unilateral knee arthritis. METHODS: ICR male mice were fed
      either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD
      mice received intra-articular injections either with Complete Freund's Adjuvant
      (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous
      pain-like behaviors and knee edema were assessed for 26 days. At day 26 post
      first CFA injection, serum levels of IL-1beta, IL-6, and RANKL were measured by
      ELISA, and microcomputed tomography analysis of knee joints was performed.
      RESULTS: HFD-fed mice injected with CFA showed greater spontaneous pain-like
      behaviors of the affected extremity as well as a decrease in the weight-bearing
      index compared to SD-fed mice injected with CFA. Knee edema was not significantly
      different between diets. HFD significantly exacerbated arthritis-induced bone
      loss at the distal femoral metaphysis but had no effect on femoral diaphyseal
      cortical bone. HFD did not modify serum levels of proinflammatory cytokines.
      CONCLUSIONS: HFD exacerbates pain-like behaviors and significantly increases the
      magnitude of periarticular trabecular bone loss in a murine model of unilateral
      arthritis.

PMID- 27030573
TI  - Proteomic analysis of exosomal cargo: the challenge of high purity vesicle
      isolation.
AB  - The re-discovery of exosomes as intercellular messengers with high potential for
      diagnostic and therapeutic utility has led to them becoming a popular topic of
      research in recent years. One of the essential research areas in this field is
      the characterization of exosomal cargo, which includes numerous non-randomly
      packed proteins and nucleic acids. Unexpectedly, a very challenging aspect of
      exploration of extracellular vesicles has turned out to be their effective and
      selective isolation. The plurality of developed protocols leads to qualitative
      and quantitative variability in terms of the obtained exosomes, which
      significantly affects the results of downstream analyses and makes them difficult
      to compare, reproduce and interpret between research groups. Currently, there is
      a general consensus among the exosome-oriented community concerning the urgent
      need for the optimization and standardization of methods employed for the
      purification of these vesicles. Hence, we review here several strategies for
      exosome preparation including ultracentrifugation, chemical precipitation,
      affinity capturing and filtration techniques. The advantages and disadvantages of
      different approaches are discussed with special emphasis being placed on their
      adequacy for proteomics applications, which are particularly sensitive to sample
      quality. We conclude that certain methods, exemplified by ultracentrifugation
      combined with iodixanol density gradient centrifugation or gel filtration,
      although labor-intensive, provide superior quality exosome preparations suitable
      for reliable analysis by mass spectrometry.

PMID- 27030574
TI  - Single- and few-layer WTe2 and their suspended nanostructures: Raman signatures
      and nanomechanical resonances.
AB  - Single crystal tungsten ditelluride (WTe2) has recently been discovered to
      exhibit non-saturating extreme magnetoresistance in bulk; it has also emerged as
      a new layered material from which atomic layer crystals can be extracted. While
      atomically thin WTe2 is attractive for its unique properties, little research has
      been conducted on single- and few-layer WTe2. Here we report the isolation of
      single- and few-layer WTe2, as well as the fabrication and characterization of
      the first WTe2 suspended nanostructures. We have observed new Raman signatures of
      single- and few-layer WTe2 that have been theoretically predicted but have not
      been reported to date, in both on-substrate and suspended WTe2 flakes. We have
      further probed the nanomechanical properties of suspended WTe2 structures by
      measuring their flexural resonances, and obtain a Young's modulus of E(Y) ~ 80
      GPa for the suspended WTe2 flakes. This study paves the way for future
      investigations and utilizations of the multiple new Raman fingerprints of single-
      and few-layer WTe2, and for explorations of mechanical control of WTe2 atomic
      layers.

PMID- 27030575
TI  - Endurance exercise increases skeletal muscle kynurenine aminotransferases and
      plasma kynurenic acid in humans.
AB  - Physical exercise has emerged as an alternative treatment for patients with
      depressive disorder. Recent animal studies show that exercise protects from
      depression by increased skeletal muscle kynurenine aminotransferase (KAT)
      expression which shifts the kynurenine metabolism away from the neurotoxic
      kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present
      study, we investigated the effect of exercise on kynurenine metabolism in humans.
      KAT gene and protein expression was increased in the muscles of endurance-trained
      subjects compared with untrained subjects. Endurance exercise caused an increase
      in plasma KYNA within the first hour after exercise. In contrast, a bout of high
      intensity eccentric exercise did not lead to increased plasma KYNA concentration.
      Our results show that regular endurance exercise causes adaptations in kynurenine
      metabolism which can have implications for exercise recommendations for patients
      with depressive disorder. 

PMID- 27030576
TI  - Prognostic value of interferon-gamma release assays, a population-based study
      from a TB low-incidence country.
AB  - BACKGROUND: The ability of interferon-gamma release assays to predict the
      development of TB has been investigated in many studies, but few cases develop TB
      during follow-up limiting the generalisation of results. METHODS: We assessed
      QuantiFERON-TB Gold In-Tube test (QFT) results from 15 980 Danish individuals and
      data on all TB cases in Denmark from 2005 to 2012 and determined the predictive
      value of the QFT for coprevalent TB (0-90 days after testing) and incident TB
      (>90 days). RESULTS: Coprevalent TB was diagnosed in 10.7% (183/1703) and 0.3%
      (38/13 463) cases with a positive and negative QFT, respectively. For the QFT
      positive cases, coprevalent TB was more frequent among persons <35 years compared
      with those >35  years (19.3% vs 7.2%, p<0.001). The cohort was followed-up for 52
      807 person-years, median follow-up time was 3.36 years. For incident TB, the
      positive and negative predictive values (PPV and NPV) were 1.32% and 99.85%,
      respectively. Incidence rates (IR) for incident TB among QFT-positives and QFT
      negatives were 383 per 10(5) and 45 per 10(5) person-years, respectively. Among
      cases with a positive QFT, IR for incident TB was associated with time interval
      since QFT (<2 years, p<0.001), but not with age (<35 years, p=0.087).
      CONCLUSIONS: We confirmed a high NPV of the QFT and found positive QFT associated
      with a higher risk of subsequent incident TB. Overall, the PPV for incident cases
      was 1.32%, and development of incident TB was associated with time interval after
      the QFT, but not with age.

PMID- 27030577
TI  - Are welders more at risk of respiratory infections? Findings from a cross
      sectional survey and analysis of medical records in shipyard workers: the WELSHIP
      project.
AB  - BACKGROUND: Exposure to welding fume increases the risk of pneumococcal
      infection; whether such susceptibility extends to other respiratory infections is
      unclear. We report findings from a survey and from medical consultation data for
      workers in a large shipyard in the Middle East. METHODS: Between January 2013 and
      December 2013, we collected cross-sectional information from 529 male workers
      variously exposed to welding fume. Adjusted ORs for respiratory symptoms (cough,
      phlegm, wheezing, shortness of breath and 'chest illness') were estimated using
      multivariable logistic regression. Subsequently, we examined consultation records
      from 2000 to 2011 for 15 954 workers who had 103 840 consultations for
      respiratory infections; the associations between respiratory infections and
      levels of welding exposure were estimated using a count regression model with a
      negative binomial distribution. RESULTS: 13% of surveyed workers reported
      respiratory symptoms with a higher prevalence in winter, particularly among
      welders. The adjusted OR in welders versus other manual labourers was 1.72 (95%
      CI 1.02 to 3.01) overall and 2.31 (1.05 to 5.10) in winter months; no effect was
      observed in summer. The risk of consultation for respiratory infections was
      higher in welders than in manual labourers, with an adjusted incidence rate ratio
      of 1.45 (1.59 to 1.83) overall, 1.47 (1.42 to 1.52) in winter and 1.33 (1.23 to
      1.44) in summer (interaction, p<0.001). CONCLUSIONS: The observation that
      respiratory symptoms and consultations for respiratory infection in welders are
      more common in winter may indicate an enhanced vulnerability to a broad range of
      infections. If confirmed, this would have important implications for the
      occupational healthcare of a very large, global workforce.

PMID- 27030578
TI  - The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and
      minimum important difference.
AB  - BACKGROUND: The EQ-5D, a generic health status questionnaire that is widely used
      in health economic evaluation, was recently expanded to the EQ-5D-5L to address
      criticisms of unresponsiveness and ceiling effect. AIMS: To describe the
      validity, responsiveness and minimum important difference of the EQ-5D-5L in
      COPD. METHODS: Study 1: The validity of the EQ-5D-5L utility index and visual
      analogue scale (EQ-VAS) was compared with four established disease-specific
      health status questionnaires and other measures of disease severity in 616 stable
      outpatients with COPD. Study 2: The EQ-5D-5L utility index and EQ-VAS were
      measured in 324 patients with COPD before and after 8 weeks of pulmonary
      rehabilitation. Distribution and anchor-based approaches were used to estimate
      the minimum important difference. RESULTS: There were moderate-to-strong
      correlations between utility index and EQ-VAS with disease-specific
      questionnaires (Pearson's r=0.47-0.72). A ceiling effect was seen in 7% and 2.6%
      of utility index and EQ-VAS. Utility index decreased (worsening health status)
      with indices of worsening disease severity. With rehabilitation, mean (95% CI)
      changes in utility index and EQ-VAS were 0.065 (0.047 to 0.083) and 8.6 (6.5 to
      10.7), respectively, with standardised response means of 0.39 and 0.44. The mean
      (range) anchor estimates of the minimum important difference for utility index
      and EQ-VAS were 0.051 (0.037 to 0.063) and 6.9 (6.5 to 8.0), respectively.
      CONCLUSIONS: The EQ-5D-5L is a valid and responsive measure of health status in
      COPD and may provide useful additional cost-effectiveness data in clinical
      trials.

PMID- 27030579
TI  - Five minutes with . . . Ian Green.

PMID- 27030580
TI  - Phenyliodonium Diacetate Mediated Oxidative Functionalization of Styrenes with
      Molecular Oxygen: Synthesis of alpha-Oxygenated Ketones.
AB  - Synthesis of alpha-oxygenated ketones from styrenes mediated by phenyliodonium
      diacetate in the presence of molecular oxygen and N-hydroxyphthalimide or N
      hydroxybenzotriazole has been described. Addition of carbonyl oxygen at the alpha
      position and formation of C-O bond at the beta-position of styrenes was achieved
      under metal-free conditions. The present method is applicable for wide range of
      styrenes with a variety of functional groups. 

PMID- 27030581
TI  - Electrochemical lithium-ion storage properties of quinone molecules encapsulated
      in single-walled carbon nanotubes.
AB  - We investigated the electrochemical lithium-ion storage properties of 9,10
      anthraquinone (AQ) and 9,10-phenanthrenequinone (PhQ) molecules encapsulated in
      the inner hollow core of single-walled carbon nanotubes (SWCNTs). The structural
      properties of the obtained encapsulated systems were characterized by electron
      microscopy, synchrotron powder X-ray diffraction (XRD), Fourier transform
      infrared (FTIR) spectroscopy and Raman spectroscopy. We found that almost all
      quinone molecules encapsulated in the SWCNTs can store Li-ions reversibly.
      Interestingly, the undesired capacity fading, which comes from the dissolution of
      quinone molecules into the electrolyte, was suppressed by the encapsulation. It
      was also found that the overpotential of AQ was decreased by the encapsulation,
      probably due to the high-electric conductivity of SWCNTs.

PMID- 27030582
TI  - A Multilaboratory Toxicological Assessment of a Panel of 10 Engineered
      Nanomaterials to Human Health--ENPRA Project--The Highlights, Limitations, and
      Current and Future Challenges.
AB  - ENPRA was one of the earlier multidisciplinary European Commission FP7-funded
      projects aiming to evaluate the risks associated with nanomaterial (NM) exposure
      on human health across pulmonary, cardiovascular, hepatic, renal, and
      developmental systems. The outputs from this project have formed the basis of
      this review. A retrospective interpretation of the findings across a wide range
      of in vitro and in vivo studies was performed to identify the main highlights
      from the project. In particular, focus was placed on informing what advances were
      made in the hazard assessment of NM, as well as offering some suggestions on the
      future of "nanotoxicology research" based on these observations, shortcomings,
      and lessons learned from the project. A number of issues related to the hazard
      assessment of NM are discussed in detail and include use of appropriate NM for
      nanotoxicology investigations; characterization and dispersion of NM; use of
      appropriate doses for all related investigations; need for the correct choice of
      experimental models for risk assessment purposes; and full understanding of the
      test systems and correct interpretation of data generated from in vitro and in
      vivo systems. It is hoped that this review may assist in providing information in
      the implementation of guidelines, model systems, validation of assessment
      methodology, and integrated testing approaches for risk assessment of NM. It is
      vital to learn from ongoing and/or completed studies to avoid unnecessary
      duplication and offer suggestions that might improve different aspects of
      experimental design. 

PMID- 27030583
TI  - Exposure to Power-Frequency Magnetic Fields and the Risk of Infertility and
      Adverse Pregnancy Outcomes: Update on the Human Evidence and Recommendations for
      Future Study Designs.
AB  - Infertility and adverse pregnancy outcomes are significant public health concerns
      with global prevalence. Over the past 35 years, research has addressed whether
      exposure to power-frequency magnetic fields is one of the etiologic factors
      attributed to these conditions. However, no apparent authoritative reviews on
      this topic have been published in the peer-reviewed literature for nearly 15
      years. This review provides an overview and critical analysis of human studies
      that were published in the peer-reviewed literature between 2002 and July 2015.
      Using PubMed, 13 epidemiology studies published during this time frame that
      concern exposure to magnetic fields and adverse prenatal (e.g., miscarriage),
      neonatal (e.g., preterm birth or birth defects), and male fertility (e.g., poor
      semen quality) outcomes were identified. Some of these studies reported
      associations whereas others did not, and study design limitations may explain
      these inconsistencies. Future investigations need to be designed with these
      limitations in mind to address existing research gaps. In particular, the
      following issues are discussed: (1) importance of selecting the appropriate study
      population, (2) need for addressing confounding due to unmeasured physical
      activity, (3) importance of minimizing information bias from exposure measurement
      error, (4) consideration of alternative magnetic field exposure metrics, and (5)
      implications and applications of personal exposure data that are correlated
      within female-male couples. Further epidemiologic research is needed, given the
      near ubiquitous exposures to power-frequency magnetic fields in the general
      population.

PMID- 27030584
TI  - Immunoglobulin G-dependent enhancement of the infection with Coxsackievirus B4 in
      a murine system.
AB  - It was demonstrated that specific IgG can enhance the infection with CV-B4, in
      vitro, in the human system. This enhancement could be involved in the
      pathophysiology of CV-B4 induced diseases. To investigate further the role of
      enhancing IgG in the infection with CV-B4 E2 in vivo, animal models are needed.
      Therefore, it was decided to assess whether inoculation of CV-B4 E2 to mice
      results in the appearance of IgG able to enhance the infection with this virus.
      Swiss albino mice were inoculated with CV-B4 E2 intraperitoneally. Serum samples
      were obtained from tail vein blood collected from day 0 to day 80 p.i. IgG were
      isolated by Protein G affinity chromatography. Seroneutralisation assays were
      carried out. In total murine spleen cells cultures inoculated with CV-B4 E2 mixed
      with various dilutions of serum or IgG samples, the enhancing activity was
      assayed through i) the antiviral activity titer of supernatants ii) the detection
      of intracellular viral RNA by RT-PCR iii) the level of infectious particles in
      supernatants. In most serum samples (76/105), neutralizing and enhancing
      activities were detected peaking between days 14 and 30 p.i and were higher in
      sera from mice inoculated with 2.10(6) TCID50 units than with lower doses. The
      enhancing activity was due to the IgG-enriched fraction of serum from CV-B4 E2
      infected animals but not from control animals. These data show that IgG from
      immune mice can enhance the infection of splenocytes with CV-B4 E2 in vitro and
      open the way to explore whether such an enhancing activity can play a role in
      vivo.

PMID- 27030585
TI  - Age at Vaccination and Timing of Infection Do Not Alter Vaccine-Associated
      Enhanced Respiratory Disease in Influenza A Virus-Infected Pigs.
AB  - Whole inactivated virus (WIV) vaccines are widely used in the swine industry to
      reduce clinical disease against homologous influenza A virus (IAV) infection. In
      pigs experimentally challenged with antigenically distinct heterologous IAV of
      the same hemagglutinin subtype, WIV vaccinates have been shown to develop vaccine
      associated enhanced respiratory disease (VAERD). We evaluated the impact of
      vaccine valency, age at vaccination, and duration between vaccination and
      challenge on the development of VAERD using vaccine containing delta1-H1N2 and
      challenge with pandemic H1N1 (pH1N1) virus. Pigs were vaccinated with monovalent
      WIV MN08 (delta1-H1N2) and bivalent (delta1-H1N2-H3N2 or delta1-H1N2-pH1N1)
      vaccines and then were challenged with pH1N1 at 3 weeks postboost (wpb). Another
      group was vaccinated with the same monovalent WIV and challenged at 6 wpb to
      determine if the time postvaccination plays a role in the development of VAERD.
      In a follow-up study, the impact of age of first WIV vaccination (at 4 versus 9
      weeks of age) with a boost 3 weeks later (at 7 versus 12 weeks of age) was
      evaluated. A monovalent live-attenuated influenza virus (LAIV) vaccine
      administered at 4 and 7 weeks of age was also included. All mismatched WIV groups
      had significantly higher lung lesions than the LAIV, bivalent MN08-CA09, and
      control groups. Age of first vaccination or length of time between booster dose
      and subsequent challenge did not alter the development of VAERD in WIV-vaccinated
      pigs. Importantly, the mismatched component of the bivalent MN08-CA09 WIV did not
      override the protective effect of the matched vaccine component.

PMID- 27030587
TI  - Opsonophagocytic Assay To Evaluate Immunogenicity of Nontyphoidal Salmonella
      Vaccines.
AB  - Nontyphoidal Salmonella (NTS) invasive infections are an important cause of
      morbidity and mortality in sub-Saharan Africa. Several vaccines are in
      development to prevent these infections. We describe an NTS opsonophagocytic
      killing assay that uses HL-60 cells and baby rabbit complement to quantify
      functional antibodies elicited by candidate NTS vaccines.

PMID- 27030586
TI  - Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a
      Vaccine Antigen.
AB  - Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to
      DENV4) that affect millions of people worldwide, causing a significant number of
      deaths. There are vaccines based on chimeric viruses, but they still are not in
      clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are
      promising alternatives to those based on whole virus or structural proteins. The
      DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based
      immune responses in humans. In this study, we purified a soluble recombinant form
      of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after
      optimization of expression conditions and purification steps. The purified DENV2
      NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected
      patients in an epitope-conformation-dependent manner. In addition, immunization
      of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and
      expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells.
      Moreover, mice immunized with purified NS5 were partially protected from lethal
      challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These
      results indicate that the recombinant NS5 protein preserves immunological
      determinants of the native protein and is a promising vaccine antigen capable of
      inducing protective immune responses.

PMID- 27030588
TI  - Field-Friendly Test for Monitoring Multiple Immune Response Markers during Onset
      and Treatment of Exacerbated Immunity in Leprosy.
AB  - Acute inflammatory reactions represent the major cause of irreversible neuropathy
      in leprosy. These tissue-destroying episodes have considerable overlap with acute
      immunological complications (flares) in several chronic (autoimmune) diseases
      that similarly warrant early detection. However, the lack of diagnostic tests
      impedes early diagnosis of these reactions. Here, we evaluated a user-friendly
      multiplex lateral flow assay for the simultaneous detection of IP-10 and anti
      phenolic glycolipid I antibodies for longitudinally monitoring early onset and
      treatment of leprosy reactions.

PMID- 27030589
TI  - Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the
      Wild-Type Cytolytic Toxin.
AB  - Staphylococcus aureus alpha-hemolysin (Hla) assembles into heptameric pores on
      the host cell membrane, causing lysis, apoptosis, and junction disruption.
      Herein, we present the design of a newly engineered S. aureus alpha-toxin,
      HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is
      able to form heptamers in aqueous solution in the absence of lipophilic
      substrata, and its structure, obtained by transmission electron microscopy and
      single-particle reconstruction analysis, resembles the cap of the wild-type
      cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and
      to its receptor ADAM10 and to lack hemolytic and cytotoxic activity.
      Immunological studies using human sera as well as sera from mice convalescent
      from S. aureus infection suggested that the heptameric conformation of HlaPSGS
      mimics epitopes exposed by the cytolytic Hla pore during infection. Finally,
      immunization with this newly engineered Hla generated high protective immunity
      against staphylococcal infection in mice. Overall, this study provides
      unprecedented data on the natural immune response against Hla and suggests that
      the heptameric HlaPSGS is a highly valuable vaccine candidate against S. aureus.

PMID- 27030591
TI  - Tobacco point-of-sale advertising in downtown Buenos Aires, Argentina and
      compliance with the new tobacco advertising restrictions.

PMID- 27030590
TI  - Novel Respiratory Syncytial Virus-Like Particle Vaccine Composed of the
      Postfusion and Prefusion Conformations of the F Glycoprotein.
AB  - Respiratory syncytial virus (RSV) is the leading cause of severe respiratory
      disease in infants and children and represents an important global health burden
      for the elderly and the immunocompromised. Despite decades of research efforts,
      no licensed vaccine for RSV is available. We have developed virus-like particle
      (VLP)-based RSV vaccines assembled with the human metapneumovirus (hMPV) matrix
      protein (M) as the structural scaffold and the RSV fusion glycoprotein (F) in
      either the postfusion or prefusion conformation as its prime surface immunogen.
      Vaccines were composed of postfusion F, prefusion F, or a combination of the two
      conformations and formulated with a squalene-based oil emulsion as adjuvant.
      Immunization with these VLP vaccines afforded full protection against RSV
      infection and prevented detectable viral replication in the mouse lung after
      challenge. Analyses of lung cytokines and chemokines showed that VLP vaccination
      mostly induced the production of gamma interferon (IFN-gamma), a marker of the
      Th1-mediated immune response, which is predominantly required for viral
      protection. Conversely, immunization with a formalin-inactivated RSV (FI-RSV)
      vaccine induced high levels of inflammatory chemokines and cytokines of the Th2-
      and Th17-mediated types of immune responses, as well as severe lung inflammation
      and histopathology. The VLP vaccines showed restricted production of these immune
      mediators and did not induce severe bronchiolitis or perivascular infiltration as
      seen with the FI-RSV vaccine. Remarkably, analysis of the serum from immunized
      mice showed that the VLP vaccine formulated using a combination of postfusion and
      prefusion F elicited the highest level of neutralizing antibody and enhanced the
      Th1-mediated immune response.

PMID- 27030592
TI  - Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases.
AB  - The term oligomeropathies defines the neurodegenerative disorders associated with
      protein misfolding, where small soluble aggregates (oligomers 4-200 KDa) are the
      cause of neuronal dysfunction and are responsible for spreading the pathology.
      The ability of these soluble beta-sheet conformers to induce neuronal damage has
      been investigated in direct challenge with the monomeric and fibrillary
      structures, showing that only the oligomeric species affected the neurons. beta
      amyloid oligomers were initially purified from Alzheimer brains and obtained
      using synthetic peptides. Together with the neuronal death, synaptic dysfunction,
      loss of spines, and LTP impairment were seen with the direct application of beta
      amyloid oligomers. Similar results have been described with proteins associated
      with other neurodegenerative disorders. The biological activities of oligomeric
      forms of alpha synuclein have been described in Parkinson's disease and Lewy body
      dementia. Detrimental effects have been associated with the oligomeric forms of
      prion, tau, and huntingtin, the key proteins in prion diseases, frontotemporal
      dementia, and Huntington's disease, respectively. The molecular mechanisms of the
      oligomer-related toxic effects can be summarized under three headings:
      nonspecific perturbance of cellular and intracellular membranes, specific
      interaction with various cellular entities, and amyloid pore channel formation.
      To characterize and distinguish oligomer actions better, we compared the ability
      of beta amyloid and alpha synuclein oligomers to induce cognitive impairment when
      applied directly into the brain in the same acute mouse model. We also
      investigated the role of inflammatory components. (c) 2016 International
      Parkinson and Movement Disorder Society.

PMID- 27030593
TI  - Long range recognition and selection in IDPs: the interactions of the C-terminus
      of p53.
AB  - The C-terminal domain of p53 is an extensively studied IDP, interacting with
      different partners through multiple distinct conformations. To explore the
      interplay between preformed structural elements and intrinsic fluctuations in its
      folding and binding we combine extensive atomistic equilibrium and non
      equilibrium simulations. We find that the free peptide segment rapidly
      interconverts between ordered and disordered states with significant populations
      of the conformations that are seen in the complexed states. The underlying global
      folding-binding landscape points to a synergistic mechanism in which recognition
      is dictated via long range electrostatic recognition which results in the
      formation of reactive structures as far away as 10 A, and binding proceeds with
      the steering of selected conformations followed by induced folding at the target
      surface or within a close range. 

PMID- 27030594
TI  - Somatic PIK3CA mutations as a driver of sporadic venous malformations.
AB  - Venous malformations (VM) are vascular malformations characterized by enlarged
      and distorted blood vessel channels. VM grow over time and cause substantial
      morbidity because of disfigurement, bleeding, and pain, representing a clinical
      challenge in the absence of effective treatments (Nguyenet al, 2014; Uebelhoeret
      al, 2012). Somatic mutations may act as drivers of these lesions, as suggested by
      the identification of TEK mutations in a proportion of VM (Limayeet al, 2009). We
      report that activating PIK3CA mutations gives rise to sporadic VM in mice, which
      closely resemble the histology of the human disease. Furthermore, we identified
      mutations in PIK3CA and related genes of the PI3K (phosphatidylinositol 3
      kinase)/AKT pathway in about 30% of human VM that lack TEK alterations. PIK3CA
      mutations promote downstream signaling and proliferation in endothelial cells and
      impair normal vasculogenesis in embryonic development. We successfully treated VM
      in mouse models using pharmacological inhibitors of PI3Kalpha administered either
      systemically or topically. This study elucidates the etiology of a proportion of
      VM and proposes a therapeutic approach for this disease.

PMID- 27030595
TI  - Somatic activating mutations in Pik3ca cause sporadic venous malformations in
      mice and humans.
AB  - Venous malformations (VMs) are painful and deforming vascular lesions composed of
      dilated vascular channels, which are present from birth. Mutations in the TEK
      gene, encoding the tyrosine kinase receptor TIE2, are found in about half of
      sporadic (nonfamilial) VMs, and the causes of the remaining cases are unknown.
      Sclerotherapy, widely accepted as first-line treatment, is not fully efficient,
      and targeted therapy for this disease remains underexplored. We have generated a
      mouse model that faithfully mirrors human VM through mosaic expression of
      Pik3ca(H1047R), a constitutively active mutant of the p110alpha isoform of
      phosphatidylinositol 3-kinase (PI3K), in the embryonic mesoderm. Endothelial
      expression of Pik3ca(H1047R)resulted in endothelial cell (EC) hyperproliferation,
      reduction in pericyte coverage of blood vessels, and decreased expression of
      arteriovenous specification markers. PI3K pathway inhibition with rapamycin
      normalized EC hyperproliferation and pericyte coverage in postnatal retinas and
      stimulated VM regression in vivo. In line with the mouse data, we also report the
      presence of activating PIK3CA mutations in human VMs, mutually exclusive with TEK
      mutations. Our data demonstrate a causal relationship between activating Pik3ca
      mutations and the genesis of VMs, provide a genetic model that faithfully mirrors
      the normal etiology and development of this human disease, and establish the
      basis for the use of PI3K-targeted therapies in VMs.

PMID- 27030596
TI  - Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid
      beta clearance and aggregation in Alzheimer's disease.
AB  - Accumulation of amyloid-beta (Abeta) peptide in the brain is the first critical
      step in the pathogenesis of Alzheimer's disease (AD). Studies in humans suggest
      that Abeta clearance from the brain is frequently impaired in late-onset AD.
      Abeta accumulation leads to the formation of Abeta aggregates, which injure
      synapses and contribute to eventual neurodegeneration. Cell surface heparan
      sulfates (HSs), expressed on all cell types including neurons, have been
      implicated in several features in the pathogenesis of AD including its
      colocalization with amyloid plaques and modulatory role in Abeta aggregation. We
      show that removal of neuronal HS by conditional deletion of the Ext1 gene, which
      encodes an essential glycosyltransferase for HS biosynthesis, in postnatal
      neurons of amyloid model APP/PS1 mice led to a reduction in both Abeta
      oligomerization and the deposition of amyloid plaques. In vivo microdialysis
      experiments also detected an accelerated rate of Abeta clearance in the brain
      interstitial fluid, suggesting that neuronal HS either inhibited or represented
      an inefficient pathway for Abeta clearance. We found that the amounts of various
      HS proteoglycans (HSPGs) were increased in postmortem human brain tissues from AD
      patients, suggesting that this pathway may contribute directly to amyloid
      pathogenesis. Our findings have implications for AD pathogenesis and provide
      insight into therapeutic interventions targeting Abeta-HSPG interactions.

PMID- 27030597
TI  - Familial autoinflammation with neutrophilic dermatosis reveals a regulatory
      mechanism of pyrin activation.
AB  - Pyrin responds to pathogen signals and loss of cellular homeostasis by forming an
      inflammasome complex that drives the cleavage and secretion of interleukin-1beta
      (IL-1beta). Mutations in the B30.2/SPRY domain cause pathogen-independent
      activation of pyrin and are responsible for the autoinflammatory disease familial
      Mediterranean fever (FMF). We studied a family with a dominantly inherited
      autoinflammatory disease, distinct from FMF, characterized by childhood-onset
      recurrent episodes of neutrophilic dermatosis, fever, elevated acute-phase
      reactants, arthralgia, and myalgia/myositis. The disease was caused by a mutation
      in MEFV, the gene encoding pyrin (S242R). The mutation results in the loss of a
      14-3-3 binding motif at phosphorylated S242, which was not perturbed by FMF
      mutations in the B30.2/SPRY domain. However, loss of both S242 phosphorylation
      and 14-3-3 binding was observed for bacterial effectors that activate the pyrin
      inflammasome, such as Clostridium difficile toxin B (TcdB). The S242R mutation
      thus recapitulated the effect of pathogen sensing, triggering inflammasome
      activation and IL-1beta production. Successful therapy targeting IL-1beta has
      been initiated in one patient, resolving pyrin-associated autoinflammation with
      neutrophilic dermatosis. This disease provides evidence that a guard-like
      mechanism of pyrin regulation, originally identified for Nod-like receptors in
      plant innate immunity, also exists in humans.

PMID- 27030599
TI  - High-sensitivity cardiac troponin I and incident coronary heart disease among
      asymptomatic older adults.
AB  - OBJECTIVE: High-sensitivity cardiac troponin I (hs-cTnI) is a novel biomarker of
      myocardial injury and ischaemia. Our objective was to ascertain correlates of hs
      cTnI and its incremental prognostic utility for incident coronary heart disease
      (CHD) among older asymptomatic subjects. METHODS: We performed a cohort study
      among 1135 asymptomatic control participants in the ADVANCE (Atherosclerotic
      Disease, VAscular FunctioN and GenetiC Epidemiology) study at Kaiser Permanente
      Northern California and Stanford University, with follow-up through 31 December
      2014. Hs-cTnI was measured in stored baseline (2002-2004) serum samples. RESULTS:
      After a median follow-up of 11.3 years, 164 CHD events were documented. The most
      significant correlates of hs-cTnI were black race, body mass index, hypertension,
      LDL cholesterol and estimated glomerular filtration rate (eGFR) (R(2)=0.16) After
      adjustment for race/ethnicity, education level, diabetes status, ATP-III
      Framingham risk score (FRS), C reactive protein and eGFR, each 1 SD increment of
      log-transformed Hs-cTnI was associated with 1.11 (95% CI 1.01 to 1.23, p=0.04)
      increased hazard of CHD. The c-statistic increased to 0.70 from 0.68 (p=0.16) and
      the category-based net reclassification index was 18% (95% CI 8% to 30%) after
      adding hs-cTnI to the model containing the ATP-III FRS. CONCLUSIONS: Hs-cTnI
      conveys incremental prognostic information for incident CHD among asymptomatic
      older adults.

PMID- 27030598
TI  - Diversification of the antigen-specific T cell receptor repertoire after
      varicella zoster vaccination.
AB  - Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are
      two critical determinants for successful control of chronic infection. Varicella
      zoster virus (VZV) that establishes latency during childhood can escape control
      mechanisms, in particular with increasing age. We examined the TCR diversity of
      VZV-reactive CD4 T cells in individuals older than 50 years by studying three
      identical twin pairs and three unrelated individuals before and after vaccination
      with live attenuated VZV. Although all individuals had a small number of dominant
      T cell clones, the breadth of the VZV-specific repertoire differed markedly. A
      genetic influence was seen for the sharing of individual TCR sequences from
      antigen-reactive cells but not for repertoire richness or the selection of
      dominant clones. VZV vaccination favored the expansion of infrequent VZV antigen
      reactive TCRs, including those from naive T cells with lesser boosting of
      dominant T cell clones. Thus, vaccination does not reinforce the in vivo
      selection that occurred during chronic infection but leads to a diversification
      of the VZV-reactive T cell repertoire. However, a single-booster immunization
      seems insufficient to establish new clonal dominance. Our results suggest that
      repertoire analysis of antigen-specific TCRs can be an important readout to
      assess whether a vaccination was able to generate memory cells in clonal sizes
      that are necessary for immune protection. 

PMID- 27030600
TI  - Prediction and impact of failure of transradial approach for primary percutaneous
      coronary intervention.
AB  - OBJECTIVES: To determine predictors of failure of transradial approach (TRA) in
      patients with ST elevation myocardial infarction (STEMI) undergoing primary
      percutaneous coronary intervention (PCI), and develop a novel score specific for
      this population. METHODS: Consecutive patients with STEMI undergoing primary PCI
      in a tertiary care high-volume radial centre were included. TRA-PCI failure was
      categorised as primary (primary transfemoral approach (TFA)) or crossover (from
      TRA to TFA). Multivariate analysis was performed to determine independent
      predictors of TRA-PCI failure, and an integer risk score was developed. Clinical
      outcomes up to 1 year were assessed. RESULTS: From January 2006 to January 2011,
      2020 patients were studied. Primary TRA-PCI failure occurred in 111 (5%) patients
      and crossover to TFA in 44 (2.2%) patients. Independent predictors of TRA-PCI
      failure were: weight <=65 kg (OR: 3.0; 95% CI 1.9 to 4.8, p<0.0001), physician
      with <=5% TFA conversion (OR: 0.45; 95% CI 0.2 to 0.9, p=0.033), and physician
      with >=10% conversion to TFA (OR: 2.2; 95% CI 1.2 to 3.7, p=0.005), intra-aortic
      balloon pump (OR: 2.0; 95% CI 0.9 to 4.3, p=0.066), cardiogenic shock (OR: 2.8;
      95% CI 1.4 to 5.6, p=0.0035), endotracheal intubation (OR: 107; 95% CI 42 to 339,
      p<0.0001), creatinine >133 MUmol/L (OR: 3.6; 95% CI 1.9 to 6.8, p<0.0001), age
      >=75 (OR: 1.7; 95% CI 1.0 to 2.9, p=0.031), prior PCI (OR: 2.6; 95% CI 1.5 to
      4.5, p=0.0009), hypertension (OR: 1.8; 95% CI 1.2 to 2.9, p=0.009). An integer
      risk score ranging from -1 to 12 was developed, and predicted TRA-PCI failure
      from 0% to 100% (c-statistic of 0.868; 95% CI 0.866 to 0.869). Mortality at 1
      year remained significantly higher after TRA-PCI failure (adjusted OR 2.2; 95% CI
      1.2 to 3.9, p=0.011). CONCLUSIONS: In a high-volume radial centre, the incidence
      of TRA-PCI failure is low and can be accurately predicted using a 9-variables
      risk score. Since outcomes after TRA-PCI failure remained inferior, further
      effort to maximise the use of radial approach for primary PCI should be
      investigated.

PMID- 27030601
TI  - Effect of prior clopidogrel use on outcomes in medically managed acute coronary
      syndrome patients.
AB  - OBJECTIVE: We investigated whether prior clopidogrel influenced long-term
      ischaemic and bleeding risks and modified the randomised treatment effect of
      clopidogrel versus prasugrel among medically managed patients with acute coronary
      syndromes (ACS) treated with dual antiplatelet therapy. METHODS: Medically
      managed patients with ACS in the Targeted Platelet Inhibition to Clarify the
      Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial
      were randomised to clopidogrel versus prasugrel (plus aspirin), stratified by
      prior clopidogrel use. From the analysis population (n=8927), we compared two
      groups: 'clopidogrel in-hospital (n=6513)' (clopidogrel started <=72 h of
      presentation for index ACS event) and 'prior-clopidogrel (n=2414)' (on
      clopidogrel >=5 days before index hospitalisation). Treatment-related differences
      in ischaemic (all-cause death, cardiovascular (CV) death, myocardial infarction
      (MI), stroke and the composite of CV death/MI/stroke) and bleeding outcomes
      (severe/life-threatening or moderate bleeding events based on Global Use of
      Strategies to Open Occluded Coronary Arteries (GUSTO) criteria) through 30 months
      were analysed between patients in the two groups. RESULTS: Compared with
      'clopidogrel in-hospital,' 'prior clopidogrel' patients were younger (median 64
      years vs 66 years, p<0.001), more likely to have prior CV
      events/revascularisation, and had a higher frequency of CV death, MI or stroke
      through 30 months (20.8% vs 18.2%, p=0.002), with no difference in bleeding
      events (2.3% vs 3.4%, p=0.50). Randomised treatment effect (prasugrel vs
      clopidogrel) was similar for ischaemic and bleeding outcomes in both groups (all
      pinteraction>0.05). CONCLUSIONS: Patients receiving clopidogrel before admission
      for ACS and subsequently treated only medically are at higher risk for CV events
      versus those not previously receiving clopidogrel. More potent antiplatelet
      inhibition with prasugrel versus clopidogrel did not significantly reduce this
      risk. TRIAL REGISTRATION NUMBER: NCT00699998.

PMID- 27030602
TI  - Markers of Vitamin D Exposure and Esophageal Cancer Risk: A Systematic Review and
      Meta-analysis.
AB  - Vitamin D has been associated with reduced risk of many cancers, but evidence for
      esophageal cancer is mixed. To clarify the role of vitamin D, we performed a
      systematic review and meta-analysis to evaluate the association of vitamin D
      exposures and esophageal neoplasia, including adenocarcinoma, squamous cell
      carcinoma (SCC), Barrett's esophagus, and squamous dysplasia. Ovid MEDLINE,
      EMBASE, and Web of Science were searched from inception to September 2015.
      Fifteen publications in relation to circulating 25-hydroxyvitamin D [25(OH)D; n =
      3], vitamin D intake (n = 4), UVB exposure (n = 1), and genetic factors (n = 7)
      were retrieved. Higher [25(OH)D] was associated with increased risk of cancer
      [adenocarcinoma or SCC, OR = 1.39; 95% confidence interval (CI), 1.04-1.74], with
      the majority of participants coming from China. No association was observed
      between vitamin D intake and risk of cancer overall (OR, 1.03; 0.65-1.42);
      however, a nonsignificantly increased risk for adenocarcinoma (OR, 1.45; 0.65
      2.24) and nonsignificantly decreased risk for SCC (OR, 0.80; 0.48-1.12) were
      observed. One study reported a decreased risk of adenocarcinoma with higher UVB
      exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T)
      carriers (OR, 0.45; 0.00-0.91), and a suggestive association was observed for
      rs2107301. In conclusion, no consistent associations were observed between
      vitamin D exposures and occurrence of esophageal lesions. Further adequately
      powered, well-designed studies are needed before conclusions can be made. Cancer
      Epidemiol Biomarkers Prev; 25(6); 877-86. (c)2016 AACR.

PMID- 27030604
TI  - Mechanisms and implications of the link between sleep apnoea and chronic kidney
      disease.

PMID- 27030603
TI  - The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine
      Metabolism on Daily Nicotine Exposure in African American Smokers.
AB  - BACKGROUND: African American (AA) smokers experience greater tobacco-related
      disease burden than Whites, despite smoking fewer cigarettes per day (CPD).
      Understanding factors that influence daily nicotine intake in AA smokers is an
      important step toward decreasing tobacco-related health disparities. One factor
      of interest is smoking topography, or the study of puffing behavior. AIMS: (i) to
      create a model using puff characteristics, nicotine dependence, and nicotine
      metabolism to predict daily nicotine exposure, and (ii) to compare puff
      characteristics and nicotine intake from two cigarettes smoked at different times
      to ensure the reliability of the puff characteristics included in our model.
      METHODS: Sixty AA smokers smoked their preferred brand of cigarette at two time
      points through a topography device. Plasma nicotine, expired CO, and changes in
      subjective measures were measured before and after each cigarette. Total nicotine
      equivalents (TNE) was measured from 24-hour urine collected during ad libitum
      smoking. RESULTS: In a model predicting daily nicotine exposure, total puff
      volume, CPD, sex, and menthol status were significant predictors (R(2) = 0.44, P
      < 0.001). Total puff volume was significantly greater and inter-puff intervals
      were significantly shorter after ad lib smoking compared with the first cigarette
      of the day, but puffing behaviors for both cigarettes were highly correlated (r
      range = 0.69-0.89, P < 0.001) within-subjects. CONCLUSION: This is the first
      study, to our knowledge, to show that puff characteristics of individual
      cigarettes are predictive of daily nicotine intake. IMPACT: These findings
      enhance our understanding of the relationship between smoking behavior and
      nicotine intake in AA smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43.
      (c)2016 AACR.

PMID- 27030606
TI  - The Greater Manchester experiment.

PMID- 27030605
TI  - Aromatic Character of Irregular-Shaped Nanographenes.
AB  - We found that the Clar sextet formula with the maximum number of sextet rings
      cannot always be defined meaningfully for large irregular-shaped PAHs. It is true
      that edge structure is always a primary determinant of the PAH aromaticity
      pattern. In large PAH molecules, every edge structure modifies the aromaticity
      pattern near the edge, but its influence fades on going away from the edge. It
      follows that different textures of the aromaticity pattern appear near different
      edges. As a result, the entire aromaticity pattern does not always match with a
      single Clar formula or a single weighted superposed Clar formula. Such an unusual
      feature of aromaticity patterns could not have been observed distinctly if we had
      not explored the aromaticity patterns of large irregular-shaped PAH molecules
      systematically. We used the superaromatic stabilization energy (SSE) as a local
      aromaticity index, which is the only index of this kind not disturbed by the
      aromaticity of adjacent benzene rings. 

PMID- 27030607
TI  - Prolonged antiretroviral therapy is associated with fewer anal high-grade
      squamous intraepithelial lesions in HIV-positive MSM in a cross-sectional study.
AB  - OBJECTIVE: HIV-positive men who have sex with men (MSM) are at increased risk of
      anal cancer. We evaluate the risk factors for anal high-grade squamous
      intraepithelial lesion (HSIL) (the precursor of anal cancer) in HIV-positive MSM.
      METHODS: In this cross-sectional study within a cohort, 320 HIV-positive MSM were
      screened by anal cytology followed by high-resolution anoscopy (HRA) in case of
      abnormal cytology. Risk factors for anal HSIL were analysed. RESULTS: Men were
      mostly middle-aged Caucasians with median CD4+ T lymphocytes of 638 cells/uL, 87%
      on combined antiretroviral therapy (cART) for a median of 5 years. 198 anal
      cytology samples were normal. In the 122 patients with abnormal cytology, HRA
      with biopsies were performed: 12% (n=15) normal, 36% (n=44) anal low-grade
      squamous intraepithelial lesion (LSIL) and 51% (n=63) anal HSIL. Comparing
      patients with or without anal HSIL (normal cytology or normal biopsy or LSIL), we
      found in multivariate analysis significantly fewer anal HSIL in patients with
      cART >=24 months (OR 0.32 CI 95% 0.162 to 0.631, p=0.001). CONCLUSIONS: Prolonged
      cART (>=24 months) is associated with fewer anal HSIL.

PMID- 27030608
TI  - Exendin-4 protects HUVECs from t-BHP-induced apoptosis via PI3K/Akt-Bcl-2-caspase
      3 signaling.
AB  - AIMS: Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type
      2 diabetes mellitus has been substantiated, its role in cardioprotection remains
      largely unknown. In this study, we explored the effect and mechanism of exendin-4
      on tert-butyl hydroperoxide (t-BHP)-induced apoptosis in human umbilical vein
      endothelial cells (HUVECs). METHODS: HUVECs were treated with 100 umol/L t-BHP
      for 4 h, following pretreatment with 2.5-25 nmol/L exendin-4. Cell viability was
      determined using an dimethyl thiazolyl diphenyl tetrazolium salt (MTT) assay. The
      percentage of apoptotic cells was determined by fluorescence microscopy after
      Hoechst/PI staining. Expression of cysteine-aspartic acid protease-3(caspase-3),
      beta-cell lymphoma 2(Bcl-2), protein kinase B(AKT), and phosphorylated AKT was
      detected by western blotting. RESULTS: Exendin-4 reduced the percentage of cells
      undergoing apoptosis when HUVECs were exposed to t-BHP. Exendin-4 downregulated
      caspase-3 activity and increased Bcl-2 protein levels in t-BHP-treated HUVECs.
      These exendin-4-mediated effects were blocked in the presence of an inhibitor of
      phosphoinositide-3 kinase (PI3K). Exendin-4 reversed t-BHP-mediated inhibition of
      Akt phosphorylation, which was abrogated by the PI3K inhibitor, wortmannin.
      CONCLUSION: Our findings suggest that exendin-4 reduces t-BHP-induced apoptosis
      of HUVECs. Additionally, PI3K/Akt-Bcl-2-caspase-3 signaling is involved in the
      exendin-4-mediated modulation of HUVECs.

PMID- 27030609
TI  - Altered Aortic Upper Wall TDI Velocity Is Inversely Related with Left Ventricular
      Diastolic Function in Operated Tetralogy of Fallot.
AB  - OBJECTIVE: Postoperative tetralogy of Fallot (TOF) patients often develop
      progressive aortic root dilatation due to an impairment in aortic elastic
      properties. AIMS: (1) to assess aortic elasticity at the level of the aortic
      upper wall by tissue Doppler imaging (TDI); (2) to evaluate the influence of
      aortic elasticity on left ventricular (LV) diastolic function in TOF patients.
      DESIGN: Twenty-eight postoperative TOF patients (14 males, 14 females. Mean age:
      25.7 +/- 1.6 years) and 28 age- and sex-matched normal subjects were examined.
      Aortic distensibility and stiffness index were calculated. Aortic wall systolic
      and diastolic velocities, LV systolic and diastolic parameters were assessed by
      TDI. RESULTS: Aortic distensibility was significantly lower (P = .024), and
      aortic stiffness index significantly higher (P = .036) in TOF patients compared
      to controls. E/E' was significantly higher in TOF than in control group (P <
      .001). Aortic upper wall early diastolic velocity (AWEDV) was significantly
      correlated with aortic stiffness index (r: -0.42; P < .03), aortic distensibility
      (r = 0.54; P < .004), left atrial volume (r = -0.62; P = .0004), and E/E' ratio
      (r = -0.87; P < .0001). The latter relationship remained significant even when
      excluding the influence of age at surgery (r = -0.60; P < .0007) and of previous
      palliative surgery (r = -0.53; P < .02). CONCLUSIONS: Aortic elastic properties
      can be directly assessed using TDI to measure AWEDV. Aortic elasticity is
      significantly lower in postoperative TOF patients, exerting a negative effect
      also on LV diastolic function, with a potential long-term influence on clinical
      status.

PMID- 27030610
TI  - [Aspirin use in primary prevention of cardiovascular disease in China: challenges
      and dilemmas].

PMID- 27030611
TI  - [Statin therapy in primary prevention of cardiovascular diseases: where do we
      stand and what should we do?].

PMID- 27030612
TI  - [Guidelines for Nontuberculous mycobacterial and its' clinical applicability].

PMID- 27030613
TI  - [The present status of aspirin use for primary prevention among hypertensive
      outpatients in China].
AB  - OBJECTIVE: To evaluate the current status of aspirin for primary prevention in
      hypertensive outpatients in China, and the gap between aspirin use and
      guidelines. METHODS: This was a multi-center cross-sectional study and carried
      out in hypertensive patients from 46 hospitals of twenty two cities in China from
      June to December in 2009. At least 100 essential hypertensive outpatients were
      consecutively recruited from each participant hospitals according to the
      consistent inclusion criteria. The patients underwent physical examinations and
      biochemical analyses, and answered questionnaires. Based on the relevant
      guidelines, the risk assessment of cardiovascular disease (CVD) is a prerequisite
      for the proper use of aspirin in primary prevention. RESULTS: A total of 5 206
      hypertensive outpatients were included. Among them, 1 324 (25.4%) were with a
      history of CVD. Among those with no history of CVD, 2 705 patients (69.7%) were
      at high risk of CVD, and the aspirin utilization rate for primary prevention was
      29.2%, with 32.2% patients at high risk and 22.4% patients at low-medium risk of
      CVD, respectively. In the application of aspirin for CVD primary prevention, the
      inappropriate aspirin use rate in patients at low-medium risk was 23.3%.
      CONCLUSIONS: The proportion of subjects at high risk for CVD is high in
      hypertensive outpatients suggesting a wide range of application space for
      aspirin.There exists underutilization for high risk and overutilization for low
      medium risk patients in current aspirin primary prevention application.

PMID- 27030614
TI  - [The effect and safety of tirofiban on acute ST segment elevation myocardial
      infarction patients receiving no early reperfusion therapy].
AB  - OBJECTIVE: To study the efficacy and safety of tirofiban on acute ST segment
      elevation myocardial infarction (STEMI) in patients who do not receive early
      reperfusion therapy. METHODS: A total of 153 STEMI patients without early
      reperfusion therapy were randomly distributed into tirofiban group (therapeutic
      group, n=78) and non-tirofiban group (control group, n=75). Coronary angiography
      was performed on the 5(th) and 10(th) day after treatment, and percutaneous
      coronary intervention (PCI) was conducted when necessary. The differences of
      initial patency of the infarct related artery (IRA), bleeding complication and
      clinic events within 30 days between these two groups were compared. RESULTS:
      Tirofiban did not increase the percentage of patients with initial patency of IRA
      (60.3% vs 64.0%, P=0.63). The percentage of patients with thrombolysis in
      myocardial infarction (TIMI) 3 after PCI was 100.0% in tirofiban group and 97.1%
      in the control group (P=0.09). However, application of tirofiban significantly
      decreased poor myocardial perfusion rate after PCI (1.4% vs 8.8%, P=0.04). No
      significant differences were observed in major adverse cardiovascular events
      (MACE) (3.8% vs 2.7%, P=0.68) between therapeutic and control group. The same is
      true for mild (5/78 vs 4/75 cases, P=0.78) and severe hemorrhage (2/78 vs 1/75
      cases, P=0.58), and severe thrombocytopenia (2/78 vs 0/75 cases, P=0.10) between
      these two groups within 30 days. CONCLUSIONS: Tirofiban did not increase initial
      patency in STEMI patients without early reperfusion therapy. However, it can
      improve myocardial perfusion after PCI.

PMID- 27030615
TI  - [Impacts of radiofrequency ablation on quality of life of atrial fibrillation
      patients with low CHA2DS2-VASc score].
AB  - OBJECTIVE: CHADS2 and CHA2DS2-VASc scores are two widely used systems for
      evaluating the risk of stroke in patients with atrial fibrillation (AF). The
      Quality of life (QoL) after a single radiofrequency ablation (RFA) in AF patients
      with low CHADS2 score has been established. This study was designed to further
      explore the association between the QoL and AF patients with low CHA2DS2-VASc
      score after RFA. METHODS: We selected 367 AF patients with low CHA2DS2-VASc score
      (CHA2DS2-VASc<2) from the Chinese Atrial Fibrillation Registry (CAFR) between
      2011 and 2013. They all completed both baseline and 6-month Atrial Fibrillation
      Effect on Quality-of-Life (AFEQT) questionnaires. Propensity score matching was
      used to construct a final cohort of 105 patients. They were divided into two
      groups: RFA group (n=44) and non-RFA group (n=61). RESULTS: Baseline clinic
      characteristics, and each domain and global score of AFEQT were comparable
      between the two groups. Except for domain of treatment satisfaction in non-RFA
      group (mean score change from baseline to 6-month: 3.55, P= 0.13) , the other
      domains in this group (mean score change from baseline to 6-month: symptom,
      14.66; daily activities, 12.56; treatment concern, 17.69; global score, 14.71,
      all P<0.05) and all the domains in RFA group improved greatly within-group
      comparison (mean score change from baseline to 6-month: symptom, 20.42; daily
      activities, 17.1; treatment concern, 20.36; global score, 18.75; treatment
      satisfaction, 9.66, all P<0.05). No significant differences were observed in all
      domains of baseline to 6-month changes between two groups (all P>0.05).
      CONCLUSIONS: No significant changes could be viewed in QoL between RFA and non
      RFA AF patients with low CHA2DS2-VASc score, whose baseline AFEQT were balanced,
      and QoL from baseline to 6-month improves significantly.

PMID- 27030616
TI  - [The characteristics of esophagogastric junction contractile index in patients
      with gastroesophageal reflux disease or functional heartburn].
AB  - OBJECTIVE: To study the role of esophagogastric junction contractile index (EGJ
      CI) in evaluating the function of anti-reflux barrier, and in differentiating
      patients with gastroesophageal reflux disease (GERD) from those with functional
      heartburn (FH). METHODS: A total of 115 patients presenting heartburn were
      enrolled in the study from January 2012 to June 2015.All subjects had completed
      Gerd-Q questionnaire and undergone gastroscopy, 24-hour pH-impedance monitoring
      and esophageal high-resolution manometry. GERD patients were divided into as
      reflux esophagitis, acid-nonerosive reflux disease (NERD) and weakly acid-NERD
      groups. Patients with normal esophageal mucosa, normal acid exposure and negative
      proton pump inhibitor test were enrolled in FH group. EGJ-CI (mmHg.cm) as well as
      EGJ rest pressure and 4s integrated relaxation pressure (IRP 4s) were measured.
      RESULTS: Among the 115 patients, 18 were reflux esophagitis [(49.0+/-18.9) years,
      M?F=10?8], 25 were acid-NERD [(48.7+/-14.4) years, M?F=13?12], 37 were weakly
      acid-NERD [(52.0+/-14.8) years, M?F=15?22] and 35 were FH [(53.6+/-14.8),
      M?F=8?27]. No differences of Gerd-Q scores were noticed between the four groups.
      (1)Negative correlations were demonstrated between EGJ-CI and esophageal acid
      exposure time (r=-0.283, P=0.002), EGJ-CI and acid reflux events (r=-0.233,
      P=0.012), EGJ-CI and weakly acid reflux events (r=-0.213, P=0.022), EGJ-CI and
      non-acid reflux events (r=-0.200, P=0.032). (2)The value of EGJ-CI was
      significantly higher in FH patients than in the three subgroups of GERD(all
      P<0.01). EGJ rest pressure of FH group was higher than that of acid-NERD
      (P<0.01). IRP 4s in acid-NERD group was lower than that of FH and weakly acid
      NERD (P<0.05). (3)The area under curve (AUC) of EGJ-CI was higher than that of
      EGJ-CIT, EGJ rest pressure or IRP 4s(0.686 vs 0.678, 0.641 and 0.578). The cut
      off value of EGJ-CI to differentiate GERD from FH was 9.74 mmHg.cm with
      sensitivity 82.86% and specificity 51.52%. CONCLUSIONS: The EGJ-CI values are
      negatively correlated with esophageal acid exposure time, weakly acid reflux
      events and non-acid reflux events. Thus it might be used as a metric to reflect
      the anti-reflux function of EGJ. According to the cut-off value of EGJ-CI 9.74
      mmHg.cm, patients with GERD can be sensitively differentiated from patients with
      FH.

PMID- 27030617
TI  - [The prevalence and etiology of anemia in urban community dwelling elderly
      population in Beijing].
AB  - OBJECTIVE: To estimate the prevalence of anemia in urban community dwelling
      elderly population. METHODS: This study was a cross-sectional survey of
      prevalence of anemia in randomly selected community dwelling residents aged over
      65 years in Beijing. Anemia was defined as hemoglobin concentration less than 130
      g/L in men and 120 g/L in women. RESULTS: The hemoglobin concentration was
      (135.65+/-14.48) g/L in total of 1 947 eligible participants and was much higher
      in men than in women [(142.56+/-15.56) g/L vs (130.95+/-11.53) g/L, P<0.001].
      There were 288 (14.8%) patients with anemia, including 16.3%(129/789) in men and
      13.7%(159/1 158) in women. The prevalence of anemia increased significantly with
      age, which was 7.6% in 65-69 years, 10.8% in 70-74 years, 18.8% in 75-79 years
      and 24.1% over 80 years (P<0.001). Two hundred and seventy-nine (96.9%) subjects
      were mild anemia, 8 (2.8%) moderate, only 1 subject (0.3%) severe. Unexplained
      anemia was predominant, which accounted for 63.2%. Only 16.7% people were
      diagnosed as nutritional anemia, renal anemia 5.2%, anemia of chronic disease
      (ACD) 12.2%. There were 2.4% people with overlapped renal anemia and ACD.
      Compared with non-anemic subjects, more subjects with unexplained anemia
      represented macrocytosis (7.1% vs 3.2%, P=0.007). CONCLUSIONS: Anemia is a common
      health problem in urban community dwelling elderly population. Most subjects have
      anemia with unknown origin. Further investigation is needed to explore the
      mechanism and related factors of elderly anemia.

PMID- 27030618
TI  - [Improved clinical outcome of acute myeloid leukemia with FLT3-ITD mutation
      treated with sorafenib].
AB  - OBJECTIVE: To analyze the efficacy of sorafenib on the treatment of patients
      diagnosed as acute myeloid leukemia(AML) with FLT3-ITD mutation. METHODS: From
      January 2012 to February 2015, 42 cases of AML with FLT3-ITD mutation according
      to MICM (morphology, immunology, cytogenetics and molecular) diagnosis system in
      our hospital were retrospectively analyzed. Thirty-two cases were refractory to
      chemotherapy or relapsed, who were treated with sorafenib or combined with
      chemotherapy. Ten patients relapsed after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT), who were retreated with sorafenib or combined with
      donor lymphocyte infusion (DLI) or chemotherapy. In the first group, 13 of 32
      patients accepted allo-HSCT. RESULTS: The overall response rate of all 42
      patients was 73.8%, including 4 (9.5%) complete molecular remission (CMR), 9
      (21.4%) complete remission (CR), 8 (19%) complete remission with incomplete
      hematologic recovery (CRi), 10 (23.8%) partial remission (PR), and 11 (26.2%)
      none remission (NR). The response rate of sorafenib alone for 17 patients was
      70.6%, and that of sorafenib plus chemotherapy was 66.7% (P=0.555). Thirteen
      patients who received allo-HSCT included 6 CMR/CR/CRi, 4 PR, and 3 NR before
      transplant. The 2-year overall survival (OS) rate and progress free survival
      (PFS) rate in all patients were 36.9% and 28.7%, and the corresponding median
      time were 18 months and 9 months respectively. The 2-year OS rate in 23 patients
      who received sorafenib combined with allo-HSCT was superior to that in 19
      patients not receiving allo-HSCT (45.5% vs 23.9%, P=0.041), so was PFS rate
      (44.0% vs 9.7%, P=0.014). Twelve cases died of disease progression, four of
      infection, and one of chronic graft versus host disease after transplant.
      CONCLUSIONS: Sorafenib combined with chemotherapy improves response rate of AML
      patients with FLT3-ITD mutation. Those who are treated with sorafenib plus allo
      HSCT obtain better long-term survival.

PMID- 27030619
TI  - [The expression of serum endoplasmic reticulum stress protein-78 in obstructive
      sleep apnea patients].
AB  - OBJECTIVE: This study aimed to detect serum level of glucose regulated protein
      78(GRP78) in patients with obstructive sleep apnea(OSA) and explore the
      relationship between endoplasmic reticulum stress and the pathophysiology of OSA.
      METHODS: A total of 91 patients with OSA were enrolled in this study, including
      30 mild, 28 moderate and 33 severe. The other 27 obese subjects were of age,
      gender and BMI matched group. Eleven moderate or severe OSA patients were
      administrated with continuous positive airway pressure (CPAP) treatment for 24
      hours. Polysomnography, apnea hypopnea index (AHI), lowest arterial oxygen
      saturation(SaO2) and percentage of time spent at SaO2 below 90% (SIT90) were
      measured before and after sleep. Serum GRP78 was measured by ELISA. RESULTS: The
      expression of GRP78 in mild(3.42+/-0.97)MUg/L, moderate(2.67+/-1.14)MUg/L and
      severe(2.62+/-1.11)MUg/L OSA groups was significantly higher than in control
      group(1.75+/-0.41)MUg/L (P<0.05). The GRP78 level in mild OSA group was
      significantly higher than either moderate or severe OSA group (P<0.05). After 24
      h treatment of CPAP, serum GRP78 level decreased significantly [(1.77+/
      0.39)MUg/L vs(2.84+/-0.39)MUg/L; P<0.05]. CONCLUSIONS: Endoplasmic reticulum
      stress involves in the pathophysiology of patients with OSA. Higher GRP78 level
      in mild OSA patients suggests that endoplasmic reticulum related protein GRP 78
      might rise then fall during exacerbation of OSA.

PMID- 27030620
TI  - [A three years longitudinal follow-up study of pulmonary function changes in
      patients with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the characteristics and the risk factors of pulmonary
      function in patients with chronic obstructive pulmonary disease (COPD) for a 3
      year follow-up. METHODS: Subjects diagnosed as COPD were followed up for 3 years
      in the Management Center of Chronic Respiratory Disease at XINQIAO Hospital from
      September 2009 to June 2012.This was a retrospective study. Parameters related to
      respiratory function mainly first second forced expiratory volume (FEV1), COPD
      assessment test (CAT), 6 minutes walking distance (6MWD) and acute exacerbation
      were recorded during follow-up. RESULTS: Although the majority of patients were
      treated with drugs such as inhaled corticosteroid combined with long-term
      bronchial dilatation during the three years, FEV1 decreased progressively. The
      average annual decline of FEV1 was(31.80+/-61.99)ml, translating into a mean
      annual decline of(3.74+/-6.18)%. However, there were significant differences in
      changes of FEV1. Approximately, FEV1 in 78.3% (47/60) patients decreased, only
      21.7%(13/60) patients kept stable FEV1. There was a correlation between decrease
      of FEV1, FEV1%predicted and the exacerbation (r=0.298, 0.361, 0.273; P<0.05).
      Logistic regression showed that the positive bronchodilator reversibility and the
      initial FEV1 were the independent factors associated with significant changes in
      FEV1 (respectively, OR=5.54, 95%CI 1.55-19.73; OR=8.28, 95%CI 1.42-48.32).
      CONCLUSION: The changes of pulmonary function in patients with COPD are
      heterogeneous, although most patients are treated in a standard way. Nearly 80%
      patients still represent deterioration of pulmonary function. Decline of FEV1 is
      closely related to the initial pulmonary function and bronchodilator
      reversibility.

PMID- 27030621
TI  - [An analysis of latent tuberculosis infection among patients with rheumatic
      diseases].
AB  - OBJECTIVE: To investigate the incidence of latent tuberculosis infection (LTBI)
      in patients with rheumatic diseases in order to find evidence for the prevention
      of mycobacterium tuberculosis (MTB) in these patients. METHODS: From January 2013
      to July 2015, 759 patients with rheumatic diseases and 38 health controls were
      enrolled. All of them underwent interferon-gamma release assays(T-SPOT.TB)to
      screen for LTBI. Incidence of MTB infection was evaluated in different groups and
      test was used for statistical analysis between groups. RESULTS: The incidences of
      LTBI in patients and health controls were 27.27%(207/759) and 10.53%(4/38),
      respectively. In 2013, 24.66%(73/296) (standardized infection rate 23.37%)
      patients with rheumatic diseases were positive for LTBI screening test. In 2014
      and 2015, the percentages were 32.02%(73/296) (standardized infection rate was
      32.15%) and 25.96%(73/228) (standardized infection rate was 28.46%),
      respectively, which was statistically significant in these 3 groups (P=0.004).
      the infection rate in 2014 tended to be higher than that in 2013 (P=0.001). There
      were 30.24%(88/291) male and 25.43%(119/468)female patients who were considered
      as LTBI. But the difference was not significant between genders. The infection
      rates between patients older than 60 years old and less was significantly
      different, which were 45.65%(42/92) and 24.74%(165/667), respectively (P=0.000).
      As far as diseases were concerned including rheumatoid arthritis, systemic lupus
      erythematosus, spondyloarthritis and other rheumatic diseases, the incidences
      were 33.93%(57/168), 22.06%(45/204), 25.73%(44/171) and 28.24%(61/216)
      respectively, without statistical significance. CONCLUSIONS: The incidence of
      LTBI is high in patients with rheumatic diseases. Attention should be paid
      especially to elderly patients and rheumatoid arthritis patients who have
      relatively higher rates of LTBI. Careful monitoring and prevention measures are
      suggested to take in these patients.

PMID- 27030622
TI  - [Protective effect of glucagon-like peptide-1 analogue on cardiomyocytes injury
      induced by hypoxia/reoxygenation].
AB  - OBJECTIVE: To investigate the effect of glucagon-like peptide-1 (GLP-1) receptor
      agonist liraglutide on hypoxia/reoxygenation (H/R)-induced cardiomyocytes death
      under high glucose condition and the potential mechanisms. METHODS: H9C2
      cardiomyocytes were divided into 4 groups: normal glucose (N, 5 mmol/L), high
      glucose (G, 20 mmol/L), high glucose in combination with liraglutide (L, 100
      nmol/L), high glucose in combination with liraglutide and wortmannin (W, 25
      nmol/L). The apoptosis of H9C2 was detected by TUNEL assay. Nitric oxide
      synthetase(eNOS), nitric oxide (NO) and reactive oxygen(ROS) in supernatants were
      measured by enzymatic analysis. p-PI3K, PI3K, p-Akt, Akt, Bcl-2, caspase-3 were
      examined by western blotting. RESULTS: Compared with cells in N group, the
      apoptosis of H9C2 cells induced by H/R was markedly increased [(15.79+/-3.92)% vs
      (9.74+/-1.14)%, P=0.028] in G group. The same was true for ROS [(489.63+/-21.01)
      U/ml vs (338.50+/-43.60) U/ml, P<0.001] and caspase-3 levels (1.87+/-0.03 vs
      1.15+/-0.04, P<0.001), but not for Bcl-2 protein expression (1.79+/-0.06 vs
      1.89+/-0.03, P=0.047). Pretreatment of cells with liraglutide (100 nmol/L)
      prevented the cell death induced by high glucose and H/R together with decrease
      of ROS and caspase-3 levels and increase of Bcl-1 expression. Moreover, treatment
      of cells with liraglutide also significantly increased phosphorylation of PI3K
      and Akt (p-PI3K/PI3K: 0.87+/-0.07 vs 0.59+/-0.09, P=0.002; p-Akt/Akt: 0.34+/-0.01
      vs 0.08+/-0.01, P<0.001), eNOS[(41.29+/-0.56)MUmpl/L vs (37.20+/-0.52)MUmpl/L,
      P<0.001)and NO [(31.24+/-0.40)MUmpl/L vs (26.66+/-0.53)MUmpl/L, P<0.001)levels.
      Furthermore, addition of PI3K/Akt inhibitor wortmanin markedly inhibited the
      expression of p-PI3K/PI3K, p-Akt/Akt, reversed the changes of eNOS, NO, caspase-3
      and Bcl-2 by liraglutide, and abolished the protective effect of liraglutide on
      cell apoptosis. CONCLUSIONS: GLP-1 receptor agonist liraglutide treatment could
      alleviate cardiomyocytes apoptosis induced by high glucose and H/R through the
      activation of PI3K-Akt-eNOS-NO signaling pathway and inhibition of oxidative
      stress.

PMID- 27030623
TI  - Averting the legacy of kidney disease - focus on childhood.

PMID- 27030624
TI  - Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of
      blocked angiotensin II receptors in rats.
AB  - The vasodilatory effect of angiotensin 1-7 (Ang 1-7) is exerted in the vascular
      bed via Mas receptor (MasR) gender dependently. However, the crosstalk between
      MasR and angiotensin II (Ang II) types 1 and 2 receptors (AT1R and AT2R) may
      change some actions of Ang 1-7 in renal circulation. In this study by blocking
      AT1R and AT2R, the role of MasR in kidney hemodynamics was described. In
      anaesthetized male and female Wistar rats, the effects of saline as vehicle and
      MasR blockade (A779) were tested on mean arterial pressure (MAP), renal perfusion
      pressure (RPP), renal blood flow (RBF), and renal vascular resistance (RVR) when
      both AT1R and AT2R were blocked by losartan and PD123319, respectively. In male
      rats, when AT1R and AT2R were blocked, there was a tendency for the increase in
      RBF/wet kidney tissue weight (RBF/KW) to be elevated by A779 as compared with the
      vehicle (P=0.08), and this was not the case in female rats. The impact of MasR on
      renal hemodynamics appears not to be sexual dimorphism either when Ang II
      receptors were blocked. It seems that co-blockade of all AT1R, AT2R, and MasR may
      alter RBF/ KW in male more than in female rats. These findings support a
      crosstalk between MasR and Ang II receptors in renal circulation. 

PMID- 27030626
TI  - Rat white adipocytes activate p85/p110 PI3K and induce PM GLUT4 in response to
      adrenoceptor agonists or aluminum fluoride.
AB  - Adipocyte responses to adrenergic and beta-adrenoceptor(-AR) (adrenoceptor)
      regulation are not sufficiently understood, and information helpful for
      elucidating the adrenoceptor-responsive machinery is insufficient. Here we show
      by using immunoprecipitated kinase analysis with a phosphatidylinositol 3-kinase
      (PI3K) p85 antibody that PI3K activation was induced by treatment with 10 or 100
      uM norepinephrine (NE) for 15 min or with 10 mM aluminum fluoride (AF, a
      guanosine triphosphate (GTP)-binding (G) protein activator) for 20 min in white
      adipocytes (rat epididymal adipocytes) and that treatment with pertussis toxin
      (PTX, a G-protein inactivator) inhibited PI3K activation induced by the 20-min
      treatment with AF in the cells. In addition, western blot analysis revealed that
      glucose transporter 4 (GLUT4) level in the adipocyte plasma membrane (PM)
      fraction was increased by treatment with 10 uM NE, 100 uM dobutamine (DOB, a
      beta1-AR agonist), or 0.1 uM CL316243 (CL, a beta3-AR agonist) for 30 min or with
      10 mM AF for 20 min. NE or AF treatment triggered 2-deoxyglucose (2-DG) uptake
      into adipocytes under the above conditions. Our results advance the understanding
      of responses to adrenoceptor regulation in white adipocytes and provide possible
      clues for clarifying the machinery involved in adrenergic and beta-AR responses
      in the cells. 

PMID- 27030625
TI  - Prostaglandin-targeting agents and spectral heart rate variability in
      experimental partial bladder outlet obstruction in rats.
AB  - The purpose of this study was to determine the activity of the autonomic nervous
      system (ANS), using spectral analysis of the heart rate variability (HRV) in the
      model of partial bladder outlet obstruction (PBOO) in rats treated with selected
      non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam
      (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost
      F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in
      the HRV spectrum (except for HRV spectrum total power reduction with MLX). The
      use of PRX caused reduction of the total power and powers of all components of
      the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were
      observed. The obtained results suggest that the total prostaglandin synthesis
      block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS
      total activity, with decreased parasympathetic activity and a relative
      sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused
      reduction of the total ANS activity as well, however with no clear disproportion
      of any part of the ANS. Therefore, prostaglandin synthesis inhibition and
      associated decrease of parasympathetic activity may constitute an additional and
      favourable feature of NSAID pharmacodynamics in the treatment of BPH. 

PMID- 27030627
TI  - Protective effects of Quercetin and chronic moderate exercise (training) against
      oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.
AB  - Background To investigate the protective effects of Quercetin administration
      associated with chronic moderate exercise (training) on oxidative stress in the
      liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that
      performed exercise training were subjected to a swimming training program (1
      hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant,
      Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all
      animals were sacrificed and liver samples were collected for estimation: some
      oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC),
      the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase,
      CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG)
      glutathione ratio. Results Diabetic rats submitted to exercise training showed
      significantly increased the oxidative stress markers (MDA and PC) and a reduction
      of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in
      hepatic tissues. A decrease in the levels of oxidative stress markers associated
      with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio
      in the hepatic tissue were observed in Quercetin-treated diabetic trained rats.
      Conclusions These findings suggest that Quercetin administration in association
      with chronic moderate exercise exerts a protective effect in diabetes by
      attenuating hyperglycemia-mediated oxidative stress in hepatic tissue. 

PMID- 27030628
TI  - Activity/inactivity circadian rhythm shows high similarities between young
      obesity-induced rats and old rats.
AB  - The objective of the present study was to compare differences between elderly
      rats and young obesity-induced rats in their activity/inactivity circadian
      rhythm. The investigation was motivated by the differences reported previously
      for the circadian rhythms of both obese and elderly humans (and other animals),
      and those of healthy, young or mature individuals. Three groups of rats were
      formed: a young control group which was fed a standard chow for rodents; a young
      obesity-induced group which was fed a high-fat diet for four months; and an
      elderly control group with rats aged 2.5 years that was fed a standard chow for
      rodents. Activity/inactivity data were registered through actimetry using
      infrared actimeter systems in each cage to detect activity. Data were logged on a
      computer and chronobiological analysis were performed. The results showed diurnal
      activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and
      interdaily stability to be similar between the young obesity-induced group and
      the elderly control group, but different in the young control group. We have
      concluded that obesity leads to a chronodisruption status in the body similar to
      the circadian rhythm degradation observed in the elderly. 

PMID- 27030629
TI  - The effect of short-term intermittent hypoxic exposure on heart rate variability
      in a sedentary population.
AB  - While the effects of instantaneous, single-bout exposure to hypoxia have been
      well researched, little is known about the autonomic response during, or as an
      adaptation to, repeated intermittent hypoxic exposure (IHE) in a sedentary
      population. Resting heart rate variability (HRV) and exercise capacity was
      assessed in 16 participants (8 receiving IHE, [Hyp] and 8 receiving a placebo
      treatment [C]) before and after a 4-week IHE intervention. Heart rate variability
      was also measured during an IHE session in the last week of the intervention.
      Post-intervention, the root mean squared successive difference (rMSSD) increased
      substantially in Hyp (71.6 +/- 52.5%, mean change +/- 90% confidence limits)
      compared to C suggesting an increase in vagal outflow. However, aside from a
      likely decrease in submaximal exercise heart rate in the Hyp group (-5.0 +/-
      6.4%) there was little evidence of improved exercise capacity. During the week 4
      IHE measurement, HRV decreased during the hypoxic exposure (reduced R-R interval:
      -7.5 +/- 3.2%; and rMSSD: -24.7 +/- 17.3%) suggesting a decrease in the relative
      contribution of vagal activity. In summary, while 4 weeks of IHE is unlikely to
      improve maximal exercise capacity, it may be a useful means of increasing HRV in
      people unable to exercise. 

PMID- 27030630
TI  - Pitfalls during biomechanical testing - Evaluation of different fixation methods
      for measuring tendons endurance properties.
AB  - The goal of the study was to find a proper technique to fix tendon grafts into an
      INSTRON loading machine. From 8 human cadavers, 40 grafts were collected. We
      removed the bone-patella tendon-bone grafts, the semitendinosus and gracilis
      tendons, the quadriceps tendon-bone grafts, the Achilles tendons, and the
      peroneus longus tendons from each lower extremity. We tested the tendon grafts
      with five different types of fixation devices: surgical thread (Premicron 3),
      general mounting clamp, wire mesh, cement fixation, and a modified clamp for an
      INSTRON loading machine. The mean failure load in case of surgical thread
      fixation was (381N +/- 26N). The results with the general clamp were (527N +/-
      45N). The wire meshes were more promising (750N +/- 21N), but did not reach the
      outcomes we desired. Easy slippages of the ends of the tendons from the cement
      encasements were observed (253N +/- 18N). We then began to use Shi's clamp that
      could produce 977N +/- 416N peak force. We combined Shi's clamp with freezing of
      the graft and the rupture of the tendon itself demonstrated an average force of
      2198 N +/- 773N. We determined that our modified frozen clamp fixed the specimens
      against high tensile forces. 

PMID- 27030631
TI  - Morning melatonin ingestion and diurnal variation of short-term maximal
      performances in soccer players.
AB  - Aim Very few studies have investigated the temporal specificity of melatonin
      (MEL) ingestion upon short-term maximal athletic performances. The aim of the
      present study was to explore the effect of morning MEL ingestion on cognitive and
      physical performances measured in the afternoon. Methods Twelve soccer players
      from a Tunisian squad (17.9 +/- 1.3 years, 1.74 +/- 0.06 m and 62.0 +/- 8.8 kg)
      participated in the present study. They performed two testing sessions at 08:00
      h, 12:00 h and 16:00 h after either MEL (5mg) or placebo (PLA) ingestion, in a
      randomized order. During each period, the participants performed the following
      cognitive and physical tests: reaction time and vigilance tests, medicine-ball
      throw (MBT), five jumps, handgrip strength (HG), and agility tests. Results
      cognitive and physical performances were significantly higher at 16:00 h compared
      to 08:00 h during the two conditions (p < 0.05). Moreover, performances of MBT
      and HG were lower in the morning with MEL in comparison to PLA (p < 0.05).
      However, MEL ingestion did not affect physical and cognitive performances
      measured at 12:00 h and 16:00 h. Conclusion morning MEL ingestion has no
      unfavourable effect on afternoon physical and cognitive performances in soccer
      players. 

PMID- 27030632
TI  - Cardiac size of high-volume resistance trained female athletes: shaping the body
      but not the heart.
AB  - Introduction Exercise training, besides many health benefits, may result in
      cardiac remodelling which is dependent on the type and amount of exercise
      performed. It is not clear, however, whether significant adaptation in cardiac
      structure is possible in females undergoing resistance type of exercise training.
      Rigorous high volume training of most muscle groups emphasising resistance
      exercises are being undertaken by athletes of some aesthetic sports such as
      female fitness (light bodybuilding). The impact of this type of training on
      cardiac adaptation has not been investigated until now. The aim of the current
      study was to disclose the effect of high volume resistance training on cardiac
      structure and function. Methods 11 top-level female fitness athletes and 20
      sedentary age-matched controls were recruited to undergo two-dimensional
      echocardiography. Results Cardiac structure did not differ between elite female
      fitness athletes and controls (p > 0.05), and fitness athletes had a tendency for
      a smaller (p = 0.07) left ventricular (LV) mass indexed to lean body mass.
      Doppler diastolic function index (E/A ratio) and LV ejection fraction were
      similar between the groups (p > 0.05). Conclusions Elite female fitness athletes
      have normal cardiac size and function that do not differ from matched sedentary
      controls. Consequently, as high volume resistance training has no easily
      observable effect on adaptation of cardiac structure, when cardiac hypertrophy is
      present in young resistance-trained lean female, other reasons such as inherited
      cardiac disease are to be considered carefully. 

PMID- 27030633
TI  - Effect of high wavelengths low intensity light during dark period on physical
      exercise performance, biochemical and haematological parameters of swimming rats.
AB  - Nocturnal rodents should be assessed at an appropriate time of day, which leads
      to a challenge in identifying an adequate environmental light which allows animal
      visualisation without perturbing physiological homeostasis. Thus, we analysed the
      influence of high wavelength and low intensity light during dark period on
      physical exercise and biochemical and haematological parameters of nocturnal
      rats. We submitted 80 animals to an exhaustive exercise at individualised
      intensity under two different illuminations during dark period. Red light (> 600
      nm; < 15lux) was applied constantly during dark period (EI; for experimental
      illumination groups) or only for handling and assessments (SI; for standard
      illumination groups). EI led to worse haematological and biochemical conditions,
      demonstrating that EI alone can influence physiological parameters and jeopardise
      result interpretation. SI promotes normal physiological conditions and greater
      aerobic tolerance than EI, showing the importance of a correct illumination
      pattern for all researchers that employ nocturnal rats for health/disease or
      sports performance experiments. 

PMID- 27030634
TI  - Zinc supplementation prolongs the latency of hyperthermia-induced febrile
      seizures in rats.
AB  - Some studies have shown a relationship between febrile seizures and zinc levels.
      The lowest dose zinc supplementation in pentylenetetrazole seizure model has a
      protective effect. But, zinc pretreatment has no effect in maximal electroshock
      model. However, it is unclear how zinc supplementation affects hyperthermia
      induced febrile seizures. The aim of the present study was to investigate the
      effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats.
      The rats were randomly assigned to four groups. Zinc supplementation was
      commenced 5 days prior to febrile seizure induction by placing the animals in a
      water bath at 45 degrees C. We measured the rectal temperature and determined the
      febrile seizure latency, duration, and stage. In the zinc-supplemented group,
      both the seizure latency and the rectal temperature triggering seizure initiation
      were significantly higher than in the other groups. We suggest that zinc
      supplementation can positively modulate febrile seizure pathogenesis in rats. 

PMID- 27030635
TI  - Effect of sex and menstrual cycle in women on starting speed, anaerobic endurance
      and muscle power.
AB  - The aim of our study was to compare the indicators of starting speed, anaerobic
      endurance and power in women as well as men, and to investigate whether the
      values of these indicators differ in women during the follicular and luteal
      phases of the menstrual cycle. The studied group included 16 men and 16 women.
      The subjects performed the 20-second maximal cycling sprint test. The men
      performed the test twice at 14-day intervals. The women undertook the test 4
      times: twice during the middle of follicular phase and twice in the middle of
      luteal phase in separate menstrual cycles. Hormonal changes during the menstrual
      cycle do not influence anaerobic performance, starting speed or anaerobic
      endurance in women. Anaerobic performance in men is higher than in women with
      similar aerobic performance expressed as VO2max/LBM (lean body mass). A lower
      power decrease with time was noted for women than men, with a similar time of
      maintaining power in both groups. This is evidence of women's better anaerobic
      endurance compared to men. At the same time, the men had significantly better
      starting speed rates than women. 

PMID- 27030637
TI  - Indicators of dairy cow transition risks: Metabolic profiling revisited.
AB  - Periparturient disease conditions affecting transition dairy cows have been
      recognized as a critical contributor to impaired dairy performance and have
      become a focal point of herd diagnostic investigations. Over the past 40 years
      use of blood sampling in the form of metabolic profiling has been applied to herd
      diagnostics with mixed impressions of diagnostic robustness. Research has greatly
      increased our understanding of underpinning mechanisms related to cow biology,
      management, environment and their interactions responsible for peripartum
      diseases. Elevated beta-hydroxybutyrate (BHB) concentration (> 1.2 mmol/l) within
      7-10 days following calving identifies high risk cows for therapeutic
      intervention. Herd evaluations with 15-25% of first week fresh cows with elevated
      BHB indicates significant disease risk and productive losses. Elevated peripartal
      serum nonesterified fatty acids (NEFA) also indicate increased disease risk. This
      review discusses documented (BHB, NEFA) and other potential analytes using
      individual or pooled samples useful for disease risk assessment or nutritional
      status and their application in risk-based or herd screening methods of herd
      metabolic profiling diagnostics. A pooled sample approach modified from the
      original Compton Metabolic Profile allows for more economic assessment of
      multiple analytes, though interpretation and herd-size application may be
      limited. Pooled samples between 5 and 10 individuals accurately represent
      arithmetic means of individuals. Most importantly metabolic profiles must be used
      in concert with other diagnostic metrics of animal and facility evaluations, body
      condition scoring and ration evaluation to be fully useful in herd evaluations. 

PMID- 27030636
TI  - Helical 1:1 alpha/Sulfono-gamma-AA Heterogeneous Peptides with Antibacterial
      Activity.
AB  - As one of the greatest threats facing the 21st century, antibiotic resistance is
      now a major public health concern. Host-defense peptides (HDPs) offer an
      alternative approach to combat emerging multi-drug-resistant bacteria. It is
      known that helical HDPs such as magainin 2 and its analogs adopt cationic
      amphipathic conformations upon interaction with bacterial membranes, leading to
      membrane disruption and subsequent bacterial cell death. We have previously shown
      that amphipathic sulfono-gamma-AApeptides could mimic magainin 2 and exhibit
      bactericidal activity. In this article, we demonstrate for the first time that
      amphipathic helical 1:1 alpha/sulfono-gamma-AA heterogeneous peptides, in which
      regular amino acids and sulfono-gamma-AApeptide building blocks are alternatively
      present in a 1:1 pattern, display potent antibacterial activity against both Gram
      positive and Gram-negative bacterial pathogens. Small angle X-ray scattering
      (SAXS) suggests that the lead sequences adopt defined helical structures. The
      subsequent studies including fluorescence microscopy and time-kill experiments
      indicate that these hybrid peptides exert antimicrobial activity by mimicking the
      mechanism of HDPs. Our findings may lead to the development of HDP-mimicking
      antimicrobial peptidomimetics that combat drug-resistant bacterial pathogens. In
      addition, our results also demonstrate the effective design of a new class of
      helical foldamer, which could be employed to interrogate other important
      biological targets such as protein-protein interactions in the future.

PMID- 27030638
TI  - Novel polymer micelle mediated co-delivery of doxorubicin and P-glycoprotein
      siRNA for reversal of multidrug resistance and synergistic tumor therapy.
AB  - Co-delivery of chemotherapeutics and siRNA with different mechanisms in a single
      system is a promising strategy for effective cancer therapy with synergistic
      effects. In this study, a triblock copolymer micelle was prepared based on the
      polymer of N-succinyl chitosan-poly-L-lysine-palmitic acid (NSC-PLL-PA) to co
      deliver doxorubicin (Dox) and siRNA-P-glycoprotein (P-gp) (Dox-siRNA-micelle).
      Dox-siRNA-micelle was unstable in pH 5.3 medium than in pH 7.4 medium, which
      corresponded with the in vitro rapid release of Dox and siRNA in acidic
      environments. The antitumor efficacy of Dox-siRNA-micelle in vitro significantly
      increased, especially in HepG2/ADM cells, which was due to the downregulation of
      P-gp. Moreover, almost all the Dox-siRNA-micelles accumulated in the tumor region
      beyond 24 h post-injection, and the co-delivery system significantly inhibited
      tumor growth with synergistic effects in vivo. This study demonstrated the
      effectiveness of Dox-siRNA-micelles in tumor-targeting and MDR reversal, and
      provided a promising strategy to develop a co-delivery system with synergistic
      effects for combined cancer therapy. 

PMID- 27030639
TI  - Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR
      inhibitor, sirolimus induced a remakable response of rapid progressive Uterine
      PEComa.
AB  - Perivascular epithelioid cell tumor is a rare tumor. To date, there is no
      consensus of therapy to be recommended for unresectable disease. For a low
      incidence and a rarely curable disease, the finding of new therapy is essential.
      Here we report the first case of a patient with perivascular epithelioid cell
      tumor whose disease had a rapid progression after surgery and had a rapid
      remarkable response of combination therapy of a VEGFR inhibitor, sorafenib, with
      an mTOR inhibitor, sirolimus. This result may have potential to deliver a new
      treatment option and inhibiting the mTOR pathway combined with inhibiting the
      VEGF pathways may be a useful strategy for malignant PEComas.

PMID- 27030640
TI  - Modification of the classical Lancefield assay of group A streptococcal killing
      to reduce inter-donor variation.
AB  - The lack of a surrogate-of-immunity assay presents a major barrier to
      Streptococcus pyogenes research. Modification of the Lancefield assay to include
      an antibody digestion step reduced inter-donor variation and permitted detection
      of the anti-streptococcal activity of intravenous immunoglobulin and convalescent
      serum, thus facilitating retrospective evaluation of immunity using stored
      samples. 

PMID- 27030641
TI  - Magnetic bead-based nucleic acid purification kit: Clinical application and
      performance evaluation in stool specimens.
AB  - Two different methods - the semi-automated magnetic bead-based kit (SK, Stool
      DNA/RNA Purification kit(r)) and the manual membrane column-based kit (QS,
      QIAamp(r) DNA Stool Mini kit) - for purifying nucleic acids from clinical stool
      samples were compared and evaluated. The SK kit was more user-friendly than QS
      due to the reduced manual processing, partial automation, and short turnaround
      time with half cost. Furthermore, SK produced high yields in both DNA and RNA
      extractions but poor purity in RNA extraction. In the assessment of rotavirus and
      Clostridium difficile infection, both kits had equivalent or more sensitive
      performance compared with the standard method. Although SK showed some
      interference and inhibition in nucleic acid extraction, the performance,
      including the repeatability, linearity, analytical sensitivity, and matrix
      effect, was sufficient for routine clinical use. 

PMID- 27030643
TI  - Increase of patellofemoral height has decreased maximum knee flexion after total
      knee arthroplasty of posterior cruciate-substituting prosthesis in a clinical
      series.
AB  - BACKGROUND: Biomechanical studies in vitro suggested that patellofemoral (PF)
      stuffing would cause knee flexion restriction after total knee arthroplasty
      (TKA). We investigated the effect of anterior PF stuffing on the postoperative
      knee flexion after cemented TKA of posterior cruciate-substituting (PS) design.
      METHODS: A retrospective review of 140 primary TKAs for osteoarthritis with an
      average age of 68.5 was conducted. The patella was resurfaced. The height of PF
      joint and the patella thickness were evaluated radiographically, preoperatively
      and 2-year postoperatively. RESULTS: The maximum flexion angle was 129.7 degrees 
      (standard deviation: SD 16.9) pre-operatively and 129.3 degrees  (SD 11.9) 2-year
      postoperatively. The increase in height was associated with the differences in
      maximum flexion angle between preoperatively and postoperatively (R = 0.254 P <
      0.01). The patella thickness change did not show any significant influences.
      CONCLUSION: The increase in patellofemoral volume has decreased range of motion
      after total knee arthroplasty of posterior cruciate-substituting prosthesis.

PMID- 27030642
TI  - CD4(+) and CD8(+) TCRbeta repertoires possess different potentials to generate
      extraordinarily high-avidity T cells.
AB  - Recent high throughput sequencing analysis has revealed that the TCRbeta
      repertoire is largely different between CD8(+) and CD4(+) T cells. Here, we show
      that the transduction of SIG35alpha, the public chain-centric HLA
      A*02:01(A2)/MART127-35 TCRalpha hemichain, conferred A2/MART127-35 reactivity to
      a substantial subset of both CD8(+) and CD4(+) T cells regardless of their HLA-A2
      positivity. T cells individually reconstituted with SIG35alpha and different
      A2/MART127-35 TCRbeta genes isolated from CD4(+) or CD8(+) T cells exhibited a
      wide range of avidity. Surprisingly, approximately half of the A2/MART127-35 TCRs
      derived from CD4(+) T cells, but none from CD8(+) T cells, were stained by
      A2/MART127-35 monomer and possessed broader cross-reactivity. Our results suggest
      that the differences in the primary structure of peripheral CD4(+) and CD8(+)
      TCRbeta repertoire indeed result in the differences in their ability to form
      extraordinarily high avidity T cells which would otherwise have been deleted by
      central tolerance. 

PMID- 27030644
TI  - Immediate responses to individual dialogic music therapy in patients in low
      awareness states.
AB  - OBJECTIVE: The aim of this study was to analyse immediate responses to individual
      dialogic music therapy (IDMT) of patients with unresponsive wakefulness syndrome
      (UWS) and individuals in a minimally conscious state (MCS) and to develop an
      assessment tool for IDMT. METHODS: Seven patients were subjected to three
      conditions: (1) sounds and stimuli of the daily environment immediately before
      IDMT, (2) specific improvisational music therapy intended to establish a dialogue
      with the patient (IDMT) and (3) sounds and stimuli of the daily environment
      immediately after IDMT. Video recordings were analysed by six independent
      assessors using 'Music Therapy in a Vegetative or Minimally Conscious State
      (MUVES)', an assessment tool developed in this study. Diagnosis of UWS or MCS was
      established using the coma recovery scale-revised (CRS-R). RESULTS: During IDMT,
      MUVES total score was higher than during the other conditions (mean difference =
      3.36; p = 0.02). During IDMT, there was no significant difference in MUVES total
      score between the UWS and MCS sub-groups (p = 0.29). Mean inter-rater-reliability
      of MUVES total score was 0.76. CONCLUSIONS: IDMT may induce immediate responses
      in patients in low awareness states, particularly also in patients with UWS.
      MUVES appears to be an acceptably reliable assessment tool for IDMT.

PMID- 27030645
TI  - 1,25 dihydroxyvitamin D3 inhibits the proliferation of thyroid cancer stem-like
      cells via cell cycle arrest.
AB  - BACKGROUND: An anti-proliferative effect of vitamin D has been reported in
      different carcinomas, including thyroid cancer. Cancer stem cells (CSCs), a very
      small fraction of cancer cells, are widely believed to be responsible for cancer
      initiation, relapse and metastasis. OBJECTIVES: We addressed the question as to
      whether CSCs derived from the anaplastic thyroid carcinoma cell lines SW1736,
      C643, HTh74 and its doxorubicin- resistant subline HTh74R are also a target of
      vitamin D action. METHODS: The effect of calcitriol on growth of HTh74, HTh74R,
      SW1736 and C643 cell lines was investigated by cell viability assays. In stem
      enriched cells derived from thyro-spheres cell cycle analysis and apoptotic
      assays were performed. Furthermore, the role of calcitriol in the formation of
      cancer thyro-spheres and its putative differentiation-inducing effect were
      analysed. RESULTS: CSCs isolated as thyro-spheres from all the four anaplastic
      thyroid carcinoma cells expressed vitamin D receptors as did their parental
      cells. Calcitriol inhibited proliferation of anaplastic thyroid carcinoma cells
      with a more pronounced effect on doxorubicin-resistant HTh74R cells, and it
      significantly reduced the capacity to form stem cell-derived spheres and
      decreased the size of these spheres that consist of CSCs and their progenitor
      cells. As revealed by cell cycle analysis, calcitriol induced G2/M phase arrest
      in thyro-sphere cells derived cells from HTh74, HTh74R and C643 but did not
      affect apoptosis. Finally, calcitriol altered morphology of CSCs. CONCLUSION:
      Calcitriol inhibited the growth of CSCs derived from anaplastic thyroid cancer
      cells. It may also exert a pro-differentiation effect in thyroid CSCs.

PMID- 27030646
TI  - Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.
AB  - Thermal decomposition of layered zinc hydroxide double salts provides an
      interesting alternative synthesis for particles of zinc oxide. Here, we examine
      the sequence of changes occurring as zinc hydroxide chloride monohydrate
      (Zn5(OH)8Cl2.H2O) is converted to crystalline ZnO by thermal decomposition. The
      specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A
      complicating and important factor in this process is that the thermal
      decomposition of zinc hydroxide chloride is also accompanied by the formation of
      volatile zinc-containing species under certain conditions. We show that this
      volatile compound is anhydrous ZnCl2 and its formation is moisture dependent.
      Therefore, control of atmospheric moisture is an important consideration that
      affects the overall efficiency of ZnO production by this process.

PMID- 27030647
TI  - [Lay further emphasis on the treatment in critical burn].
AB  - In recent years, growth in number of mass burn casualties accompanied by large
      number of deaths, has increased, such as dust blast occurred in Kunshan in 2014
      and explosion of chemicals occurred in Tianjin in 2015. These disasters made us
      aware that our knowledge of care of mass burn casualties must be renewed, and
      therapeutic strategies currently practiced in ICU should be adopted. This paper
      introduces the concept of critical burn and provides reference on how to carry
      out fluid resuscitation, early enteral nutrition, mechanical ventilation,
      continuous renal replacement therapy, wound management, as well as infection
      control, etc. 

PMID- 27030648
TI  - [Clinical randomized controlled trial on the feasibility and validity of
      continuous blood purification during the early stage of severe burn].
AB  - OBJECTIVE: To observe and primarily evaluate the feasibility and validity of
      continuous blood purification (CBP) during the early stage of severe burn.
      METHODS: Forty-one patients with severe burn admitted to our ward from January
      2013 to July 2015, conforming to the study criteria, were divided into
      conventional treatment group (CT, n=21) and blood purification group (BP, n=20)
      according to the random number table and patient's personal consent. Patients in
      group CT received CT conforming to the traditional resuscitation principle for
      severe burn, while patients in group BP received CT and blood purification
      treatment in the mode of continuous venous-venous hemodiafiltration in addition
      up to post injury hour (PIH) 72. On post injury day (PID) 1, 2, 3, the vital
      signs, volume of fluid input, and volume of the urine output were observed and
      recorded; femoral artery blood was drawn to determine lactate, bicarbonate
      radical, and base excess, and oxygen index was calculated. At PIH 12, 24, 48, 72,
      femoral vein blood was drawn to determine white cell count, platelet count,
      neutrophils, creatine kinase-MB, creatine kinase, lactic dehydrogenase, aspartate
      transaminase (AST), alanine aminotransferase (ALT), creatinine, urea nitrogen,
      and blood glucose (the ratio of AST to ALT was calculated). The incidence of
      infection, sepsis, and multiple organ dysfunction syndrome (MODS) and the
      mortality of patients were recorded during 2 months after injury. Data were
      processed with chi-square test, analysis of variance for repeated measurement, t
      test and Wilcoxon test, and the values of P were adjusted by Bonferroni. RESULTS:
      The observation was completed in the 41 patients without exclusion. (1) There
      were no statistically significant differences in vital signs, volume of fluid
      input, and volume of the urine output of patients between two groups on PID 1, 2,
      3 (with t values from -1.64 to 1.48, P values above 0.05). (2) Compared with that
      in group CT, the level of lactate of patients in group BP declined significantly
      on PID 2 and 3 (with Z values respectively -2.37 and -2.46, P values below 0.05).
      Compared with those in group CT, the levels of bicarbonate radical and base
      excess of patients in group BP declined significantly on PID 3 (with t values
      both as -2.51, P values below 0.05). The oxygen index of patients in group BP on
      PID 3 was (370+/-98) mmHg (1 mmHg=0.133 kPa), which was significantly higher than
      that in group CT [(305+/-81) mmHg, t=2.27, P<0.05]. (3) There were no
      statistically significant differences in white cell count, platelet count,
      neutrophils, creatine kinase, lactic dehydrogenase, AST, ALT, and AST to ALT
      ratio of patients between two groups at PIH 12, 24, 48, 72 (with t values from 
      1.47 to 1.19, Z values from -1.58 to -0.03, P values above 0.05). At PIH 24, 48,
      72, the levels of creatine kinase-MB and blood glucose of patients in group BP
      were respectively (81+/-43), (55+/-34), (58+/-40) U/L and (7.9+/-2.0), (6.7+/
      0.9), (6.9+/-1.8) mmol/L, which were significantly lower than those in group CT
      [(179+/-184), (124+/-71), (103+/-57) U/L and (10.1+/-3.8), (9.1+/-2.4), (8.8+/
      4.1) mmol/L, with Z values from -3.73 to -2.02, P<0.05 or P<0.01]. Compared with
      those of patients in group CT, creatinine at PIH 48 and urea nitrogen at PIH 24,
      48, 72 were obviously lower in group BP (with t values from -4.23 to -2.44,
      P<0.05 or P<0.01). (4) During the two months after injury, the infection rate of
      patients in group BP was 60.0% (12/20), which was significantly lower than that
      in group CT [95.2% (20/21), chi(2)=5.51, P<0.05]. The incidence of sepsis and
      MODS and the mortality of patients in group BP were all lower than those in group
      CT, but there were no statistically significant differences (with chi(2) values
      from 0.22 to 2.93, P values above 0.05). CONCLUSIONS: Conducting CBP in the early
      stage of severe burn is safe and feasible, which does not obviously affect the
      vital signs, volumes of fluid input and urine output, or platelet count of
      patients, additionally, it could help protect the function of vital organs,
      eliminate stress hyperglycemia, and reduce infection rate. Clinical trial
      registration Chinese Clinical Trial Registry, ChiCTR-TRC-12002616.

PMID- 27030649
TI  - [Effect of application of pulse contour cardiac output monitoring technology on
      delayed resuscitation of patients with extensive burn in a mass casualty].
AB  - OBJECTIVE: To investigate the effect of the application of pulse contour cardiac
      output (PiCCO) monitoring technology on delayed resuscitation of patients with
      extensive burn in a mass casualty. METHODS: The clinical data of 41 patients
      injured in Kunshan dash explosion hospitalized in the First Affiliated Hospital
      of Soochow University, the 100th Hospital of the People's Liberation Army, and
      Suzhou Municipal Hospital were retrospectively analyzed. The patients were
      divided into traditional monitoring group (T, n=22) and PiCCO monitoring group
      (P, n=19) according to the monitoring technic during delayed resuscitation. The
      input volumes of electrolyte, colloids, and water of patients in the two groups
      within 2 hours after admission, the first, second, and third 8 hours post injury
      (HPI), and the first 24 HPI were recorded. The fluid infusion coefficients of
      patients in the two groups within 2 hours after admission, the first, second, and
      third 8 HPI, and the first, second, third, and fourth 24 HPI were calculated. The
      urine volume, mean arterial pressure (MAP), and central venous pressure (CVP) of
      patients in the two groups at post injury hour (PIH) 8, 16, 24, 48, 72, and 96
      were recorded. The blood lactate, base excess, hematocrit (HCT), and platelet
      count of patients in the two groups at PIH 24, 48, 72, and 96 were recorded.
      Complications and death of patients in the two groups were recorded. Data were
      processed with analysis of variance for repeated measurement, Chi-square test, t
      test, and Wilcoxon test. The deviations between figure 2 and the fluid infusion
      coefficients of the first or second 24 HPI, and the deviations between figure 1
      and the fluid infusion coefficients of the second, third or fourth 24 HPI were
      calculated, and the three groups deviations were analyzed by Pearson correlation
      analysis. RESULTS: (1) The input volumes of electrolyte of patients in group P
      were significantly more than those in group T within the first 8 and 24 HPI (with
      Z values respectively -3.506 and -2.654, P<0.05 or P<0.01), and the input volumes
      of electrolyte of patients in the two groups were similar within the other time
      periods (with Z values from -1.871 to -0.680, P values above 0.05). The input
      volumes of colloid of patients in group P were significantly less than those in
      group T within the second, third 8 HPI, and the first 24 HPI (with Z values from 
      4.720 to -2.643, P<0.05 or P<0.01), and the input volumes of colloid of patients
      in the two groups were similar within the other time periods (with Z values
      respectively -2.376 and -2.303, P values above 0.05). The input volumes of water
      of patients in the two groups were similar within each time period (with Z values
      from -1.959 to -0.241, P values above 0.05). (2) The fluid infusion coefficients
      of patients in group T within 2 hours after admission, the first, second, and
      third 8 HPI, and the first, second, third, and fourth 24 HPI were respectively
      (0.59+/-0.18), (0.70+/-0.23), (0.94+/-0.24), (0.74+/-0.14), (2.38+/-0.44),
      (1.70+/-0.56), (1.35+/-0.67), and (0.92+/-0.46) mL.kg(-1).%TBSA(-1,) and the
      values in group P were respectively (0.59+/-0.29), (0.82+/-0.37), (0.86+/-0.38),
      (0.59+/-0.24), (2.27+/-0.85), (2.13+/-0.68), (1.59+/-3.78), and (1.46+/-0.56)
      mL.kg(-1).%TBSA(-1). The fluid infusion coefficients of patients in the two
      groups were similar within 2 hours after admission, the first, second 8 HPI, and
      the first, third 24 HPI (with t values from -1.262 to 0.871, P values above
      0.05). The fluid infusion coefficient of patients in group P was significantly
      lower than that in group T within the third 8 HPI (t=2.456, P<0.05), and the
      fluid infusion coefficient of patients in group P were significantly higher than
      that in group T within the second and fourth 24 HPI (with t values respectively 
      2.234 and -3.370, P<0.05 or P<0.01). There was obviously negative correlation
      between the deviations of figure 2 and the fluid infusion coefficient of the
      first 24 HPI and that of the second 24 HPI (r=-0.438, P<0.01). There was no
      obvious correlation between the deviations of figure 1 and the fluid infusion
      coefficient of the second 24 HPI and that of the third 24 HPI (r=0.091, P>0.05).
      There was obviously positive correlation between the deviations of figure 1 and
      the fluid infusion coefficient of the second 24 HPI and that of the fourth 24 HPI
      (r=0.695, P<0.01). (3) The urine volumes and MAP of patients in the two groups
      were similar at each time point (with Z values from -1.884 to 0, P values above
      0.05). The CVP of patients in group P were significantly higher than that in
      group T at PIH 16, 24, 48, and 72 (with Z values from -4.341 to -2.213, P<0.05 or
      P<0.01), and the CVP of patients in the two groups were similar at the other time
      points (with Z values respectively -0.132 and -1.208, P values above 0.05). The
      blood lactate of patients in group P was significantly higher than that in group
      T at PIH 72 (Z= -2.958, P<0.01) , and the blood lactate of patients in the two
      groups were similar at the other time points (with Z values from -1.742 to 
      0.433, P values above 0.05). The base excess of patients in group P were
      significantly lower than that in group T at PIH 24, 48, 72, and 96 (with Z values
      from -4.970 to -4.734, P values below 0.01). The HCT of patients in the two
      groups were similar at PIH 24, 48, 72, and 96 (with Z values from -2.239 to 
      0.196, P values above 0.05). There were significant differences in the platelet
      count of patients in the two groups at PIH 24, 72, and 96 (with Z values from 
      4.578 to -2.512, P<0.05 or P<0.01). (4) There were 15 cases in group T
      accompanied by complications, and 7 cases died, while 13 cases in group P
      accompanied by complications, and 9 cases died. The occurrence of complications
      and death of patients in the two groups were similar (with chi(2) values
      respectively <0.001 and 1.306, P values above 0.05). CONCLUSIONS: On the basis of
      traditional burn shock monitoring index, the effect of fluid resuscitation in
      patients with severe burn monitored by PiCCO technology is not so good and still
      needs further clinical research.

PMID- 27030650
TI  - [Prognostic significance of serum procalcitonin in patients with extremely severe
      burn and sepsis].
AB  - OBJECTIVE: To analyze the changes in serum procalcitonin (PCT) in patients with
      extremely severe burn and sepsis, and to evaluate its clinical significance in
      the prognosis of patients. METHODS: Thirteen patients with extremely severe burn
      and sepsis injured in the aluminum dust explosion accident, which occurred in
      Kunshan of Jiangsu province, were admitted to our unit on August 2nd, 2014. They
      were involved in this retrospective study and divided into death group (n=5) and
      survival group (n=8) according to the outcome. Acute Physiology and Chronic
      Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment
      (SOFA) score at post admission hour (PAH) 24 were compared among the patients
      between two groups. Serum level of PCT, serum level of C-reactive protein (CRP),
      white cell count, neutrophils, platelet count, level of aspartate transaminase
      (AST), level of prealbumin (PA), level of creatinine, level of urea nitrogen, and
      level of blood sodium were compared among the patients between two groups in post
      admission week (PAW) 1, 2, 3, and 4. Data were processed with Fisher's exact
      test, analysis of variance for repeated measurement, t test, and Mann-Whitney
      test. Receiver operating characteristic (ROC) curves of serum PCT values were
      plotted to evaluate the predictive value for death of 13 patients in PAW 3 and 4.
      RESULTS: The differences in APACHE II score and SOFA score at PAH 24 and serum
      level of CRP, white cell count, level of AST, level of creatinine, level of urea
      nitrogen, and level of blood sodium from PAW 1 to 4 of the patients between two
      groups were not statistically significant (with t values from -1.164 to 0.587, Z
      values from -1.872 to -0.442, P values above 0.05). The serum levels of PCT in
      patients of death group in PAW 3 and 4 were respectively (15.8+/-14.9) and
      (13.6+/-5.6) ng/mL, which were significantly higher than those of survival group
      [(2.4+/-1.8) and (4.9+/-6.1) ng/mL, with Z values respectively -2.635 and -2.208,
      P<0.05 or P<0.01]. The serum levels of PCT of patients in death group and
      survival group in PAW 1 and 2 were close (with Z values respectively -0.732 and 
      1.025, P values above 0.05). Compared with those of survival group, neutrophils
      in PAW 4 was significantly increased (t=-3.690, P<0.01), the platelet count in
      PAW 4 was significantly decreased (t=4.858, P<0.01), and the level of PA in PAW 2
      was significantly increased in patients of death group (t=-2.320, P<0.05). There
      were no statistically significant differences in neutrophils, platelet count, and
      the level of PA at the other time points of patients between death group and
      survival group (with t values from -1.562 to 1.904, P values above 0.05). The
      total areas under ROC curves of serum level of PCT for predicting death of 13
      patients with extremely severe burn and sepsis in PAW 3 and 4 were respectively
      0.938 and 0.906, and 7.45 ng/mL and 8.77 ng/mL were respectively chosen as the
      optimal threshold values, with sensitivity of 75.0% and 100.0% and specificity of
      100.0% and 87.5%. CONCLUSIONS: Serum level of PCT in PAW 3 and 4 can be used as
      the vital prognostic indicators for patients with extremely severe burn and
      sepsis, and it can be considered as a guide for rational treatment in clinic.

PMID- 27030652
TI  - [Advances in the research of blast lung injury].
AB  - In recent years, a variety of explosive weapons become increasingly common used
      in regional military conflicts and terrorist bomb attacks. Meanwhile, the
      incidence of accidental explosion also showed an increase in the industries and
      daily life. The lung is the most labile organ and it is used to be severely
      injured organ in blast injury although even no signs of external injury could be
      observed on chest. Blast injury can present the symptoms such as lung rupture,
      bleeding, edema and emphysema. Respiratory dysfunction can affect oxygen supply
      to organs and systemic tissue, resulting in rapid and sustained hypoxemia and
      high mortality rate. Blast lung injury is characterized by respiratory
      disturbance and hypoxia. This article summarizes the etiology, pathogenesis,
      pathophysiological changes, diagnosis, and treatment of blast lung injury, with a
      hope to provide some useful clinical information. 

PMID- 27030653
TI  - [Expression and significance of tumor necrosis factor alpha, matrix
      metalloproteinase 2 and collagen in skin tissue of pressure ulcer of rats].
AB  - OBJECTIVE: To observe the expressions of tumor necrosis factor alpha (TNF-alpha),
      matrix metalloproteinase 2 (MMP-2) and collagen in local skin tissue of pressure
      ulcer of rats, and to explore the possible mechanism of the pathogenesis of
      pressure ulcer. METHODS: Forty male SD rats were divided into normal control
      group, 3 d compression group, 5 d compression group, 7 d compression group, and 9
      d compression group according to the random number table, with 8 rats in each
      group. The rats in normal control group did not receive any treatment, whereas
      the rats in the latter 4 groups were established the deep tissue injury model (3
      d compression group) and pressure ulcer model (the other 3 groups) on the
      gracilis muscle on both hind limbs using a way of cycle compression of ischemia
      reperfusion magnet. The rats in 3 d compression group received only three cycles
      of compression, while the compressed skin of the rats in 5 d compression group, 7
      d compression group, and 9 d compression group were cut through and received
      pressure to 5, 7 and 9 cycles after three cycles of compression, respectively.
      The rats in 3 d compression group were sacrificed immediately after receiving
      compression for 3 d (the rats in normal control group were sacrificed at the same
      time), and the rats in the other 3 groups were respectively sacrificed after
      receiving compression for 5, 7, and 9 d, and the skin tissue on the central part
      of gracilis muscle on both hind limbs were harvested. The morphology of the skin
      tissue was observed with HE staining. The expression of collagen fiber was
      observed with Masson staining. The expressions of collagen type IV and MMP-2 were
      detected by immunohistochemical method. The expressions of TNF-alpha and
      phosphorylated NF kappa B (NF-kappaB) were determined by Western blotting. Data
      were processed with one-way analysis of variance and LSD test. RESULTS: (1) In
      normal control group, the skin tissue of rats was stratified squamous epithelium,
      with the clear skin structure, and there was no obvious infiltration of
      inflammatory cells. In 3 d compression group, the skin layers of rats were clear,
      with quite a few fibroblasts, and the inflammatory cells began to infiltrate. In
      5 d compression group, 7 d compression group, and 9 d compression group, the
      epidermis of rats thickened, with the number of fibroblasts reduced, and the
      infiltration of inflammatory cells enhanced with the compressed time prolonging.
      (2) In normal control group, the collagen fibers in skin tissue of rats were
      arranged in order, with rich content. In 3 d compression group, the collagen
      fibers in skin tissue of rats were arranged orderly, with high expression level,
      which was similar to that in normal control group (P>0.05). In 5 d compression
      group and 7 d compression group, the collagen fibers in skin tissue of rats were
      arranged in disorder, with the expression level gradually reduced, which were
      significantly lower than that in normal control group (with P values below 0.01).
      In 9 d compression group, the expression of collagen fiber in skin tissue of rats
      was a little higher than that in 7 d compression group, but it was still
      significantly lower than that in normal control group (P<0.01). (3) The
      expressions of collagen type IV in skin tissue of rats in normal control group, 3
      d compression group, 5 d compression group, 7 d compression group, and 9 d
      compression group were respectively 11.0+/-2.8, 9.0+/-1.7, 8.3+/-2.8, 5.1+/-1.8,
      and 5.4+/-1.2. The expression of collagen type IV in skin tissue of rats in 3 d
      compression group was similar to that in normal control group (P>0.05). The
      expressions of collagen type IV in skin tissue of rats in 5 d compression group,
      7 d compression group, and 9 d compression group were significantly lower than
      that in normal control group (P<0.05 or P<0.01). The expression of MMP-2 in skin
      tissue of rats in 3 d compression group was similar to that in normal control
      group (P>0.05). The expressions of MMP-2 in skin tissue of rats in 5 d
      compression group, 7 d compression group, and 9 d compression group were
      significantly higher than that in normal control group (P<0.05 or P<0.01). (4)
      The expression of TNF-alpha in skin tissue of rats in normal control group was
      0.48+/-0.11, and the expressions of TNF-alpha in skin tissue of rats in 3 d
      compression group, 5 d compression group, 7 d compression group, and 9 d
      compression group were respectively 0.84+/-0.08, 1.13+/-0.19, 1.34+/-0.16, and
      1.52+/-0.23, which were all significantly higher than that in normal control
      group (with P values below 0.01). The expressions of phosphorylated NF-kappaB in
      skin tissue of rats in 3 d compression group and 9 d compression group were
      similar to that in normal control group (with P values above 0.05), and the
      expressions of phosphorylated NF-kappaB in skin tissue of rats in 5 d compression
      group and 7 d compression group were significantly higher than that in normal
      control group (P<0.05 or P<0.01). CONCLUSIONS: The high expression of MMP-2 and
      reduction of collagen induced by inflammatory reaction mediated by the high
      expression of TNF-alpha in local skin tissue of pressure ulcer of rats may be one
      of the important reasons for the formation of pressure ulcer.

PMID- 27030654
TI  - [Effects of San-huang-sheng-fu oil on peripheral circulatory disorders and foot
      ulcers in diabetic rats and the mechanisms].
AB  - OBJECTIVE: To observe the effects of San-huang-sheng-fu oil (S) on peripheral
      circulatory disorders and foot ulcers in diabetic rats and the relevant
      mechanisms. METHODS: (1) Twenty-five Wistar rats were divided into non-diabetes
      (N), diabetes and sham treatment (DS), metformin (M), S, and combined treatment
      (CT) groups according to the random number table, with 5 rats in each group. Rats
      in group N were injected with sodium citrate buffer solution, while rats in the
      other 4 groups were injected with 10 mg/mL streptozotocin to induce diabetes. In
      post injection week (PIW) 3, feet of rats in all the 5 groups received an ice
      cold stimulation to induce peripheral circulatory disorders. From PIW 9 to 12,
      rats in groups N and DS were gavaged with saline and applied with sesame oil on
      pelma of both hind limbs; rats in group M were gavaged with diluted M and applied
      with sesame oil on pelma of both hind limbs; rats in group S were gavaged with
      saline and applied with S on pelma of both hind limbs; rats in group CT were
      gavaged with diluted M and applied with S on pelma of both hind limbs. In PIW 9
      before treatment (hereinafter referred to as before treatment) and post treatment
      week (PTW) 1, 2, and 3, plantar temperature and hot pain threshold of rats were
      detected by infrared thermometer and foot tester respectively. (2) Another 25
      rats were divided and induced with diabetes (expect for group N) as above. In PIW
      9, rats in the 5 groups were inflicted with foot ulcer in the left pelma of hind
      limb by steam and received the corresponding treatment. On post treatment day
      (PTD) 3, 7, 21, and 35, the general condition and area of wounds were observed
      and measured respectively. All the rats were sacrificed on PTD 35, and wound
      tissue was collected for histomorphological observation and determination of
      expressions of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor
      (VEGF) using HE staining and immunohistochemical staining respectively. Data were
      processed with analysis of variance for repeated measurement, one-way analysis of
      variance, and Bonferroni post hoc test. RESULTS: (1) The experiment of peripheral
      circulatory disorders in diabetes. Compared with the plantar temperature of rats
      in group N, except for that in group CT in PTW 2 and groups M, S, and CT in PTW 3
      (with t values from 0.258 to 2.647, P values above 0.05), the plantar temperature
      of rats with diabetes in the 4 groups at each time point was lowered
      significantly (with t values from 2.811 to 6.066, P values below 0.05). Compared
      with the plantar temperature of rats in group DS, except for that in group CT in
      PTW 2 and 3 significantly increased (with t values respectively 3.419 and 2.863,
      P values below 0.05), the plantar temperature of rats in groups M, S, and CT
      showed no significant difference at each time point (with t values from 0.128 to
      1.654, P values above 0.05). The plantar hot pain threshold of rats was
      significantly decreased in group N than in the other 4 groups before treatment
      and group S in PTW 1 (with t values from 2.836 to 4.456, P values below 0.05).
      The plantar hot pain thresholds of rats in groups M, S, and CT were close to the
      hot pain threshold in group DS (with t values from 0.312 to 1.611, P values above
      0.05). (2) The experiment of diabetic foot ulcers. Edema existed in all the
      wounds of rats on PTD 3. The wound areas of all the rats continued to increase
      with swelling and scar formation on PTD 7. On PTD 21, the scar of rats in groups
      N, S, and CT fell off; the wounds of rats in group DS were still swollen; scar of
      rats did not fall off with dark red in the skin around the wound in group M. On
      PTD 35, wounds of rats in groups N, S, and CT were nearly healed; while wounds of
      rats in groups DS and M were still swollen and the scar around the wound failed
      to fall off. On PTD 3 and 7, the wound areas of rats with diabetes in the 4
      groups were close to those in group N (with t values from 0.111 to 1.476, P
      values above 0.05). On PTD 21, the wound area of rats in group DS was
      significantly larger than that in group N (t=5.502, P<0.01), while the wound
      areas of rats with diabetes in the other 3 groups were close to the area in group
      N (with t values from 0.544 to 1.676, P values above 0.05). On PTD 21, the wound
      area of rats in group M was close to that in group DS (t=1.895, P>0.05), while
      the wound areas of rats in groups S and CT were significantly smaller than the
      area in group DS (with t values respectively 5.809 and 3.426, P<0.05 or P<0.01).
      On PTD 35, the wound areas of rats in groups DS and M were significantly larger
      than the area in group N (with t values respectively 8.495 and 4.108, P values
      below 0.01), while the wound areas of rats in groups S and CT were close to the
      area in group N (with t values respectively 0.291 and 2.195, P values above
      0.05). On PTD 35, the wound area of rats in group M was close to that in group DS
      (t=0.897, P>0.05); while the wound areas of rats in groups S and CT were
      significantly smaller than the area in group DS (with t values respectively 6.923
      and 6.583, P values below 0.01). On PTD 35, the structures of wound tissue were
      in better integrity with less inflammatory cells and more regularly arranged
      collagen fibers around the wounds of rats in groups N, S, and CT than in groups
      DS and M. On PTD 35, the expression levels of COX-2 and VEGF in the wounds of
      rats in group DS [respectively (222+/-89)% and (55+/-12)%] were close to those in
      group M [respectively (137+/-24)% and (94+/-36)%, with t values respectively
      3.046 and 2.653, P values above 0.05]. On PTD 35, the expression level of COX-2
      in the wounds of rats in group DS was significantly higher than the expression
      levels of COX-2 in groups N, S, and CT [respectively (100+/-35)%, (91+/-42)%, and
      (109+/-17)%, with t values from 4.039 to 4.653, P values below 0.01], while the
      expression level of VEGF in the wounds of rats in group DS was significantly
      lower than the expression levels of VEGF in groups N, S, and CT [respectively
      (100+/-28)%, (143+/-12)%, and (120+/-13)%, with t values from 3.363 to 5.905,
      P<0.05 or P<0.01]. CONCLUSIONS: S can improve the plantar temperature decrease
      and pain dysesthesia of rats caused by diabetic peripheral circulatory disorders.
      It also can promote wound healing of diabetic foot ulcers in rats with down
      regulation of COX-2 and up-regulation of VEGF.

PMID- 27030655
TI  - [Prevalence of deep venous thrombosis in burn patients and its influencing
      factors].
AB  - OBJECTIVE: To investigate the prevalence of deep venous thrombosis (DVT) in burn
      patients, and to explore its influencing factors. METHODS: Clinical data of 2 506
      burn patients admitted to our ward from January 2009 to January 2014, conforming
      to the study criteria, were retrospectively analyzed. Patients were divided into
      DVT group (n=26) and non-DVT group (n=2 480) according to whether or not DVT
      occurred during hospitalization. The incidence of DVT was calculated. The
      diagnosis time and type of DVT were recorded. The data of gender, age, depth of
      burn, total burn area, location of injury, cause of injury, infection of wound,
      venous transfusion of fluid (hypertonic solution and blood), location of
      intravenous catheterization, skin grafting, timing of first skin grafting after
      injury, D-dimer, bedridden duration after injury among patients between two
      groups were compared with chi-square test and Wilcoxon test. Indexes with
      statistically significant differences between two groups were selected, and they
      were processed with multivariate logistic stepwise regression analysis to screen
      the independent risk factors of DVT. RESULTS: (1) The incidence of DVT was 1.04%
      (26/2 506). The diagnosis time of DVT was 16-62(40+/-12)d, and patients diagnosed
      as having DVT after the 20th day post injury accounted for 92.3% (24/26). All DVT
      occurred in lower limbs, with 1 case of central type, 24 cases of peripheral
      type, and 1 case of mixed type. (2) There were no statistically significant
      differences in gender, location of injury (upper limbs, trunk, head and face),
      cause of injury, jugular vein catheterization, skin grafting, and timing of first
      skin grafting after injury among patients between two groups (with chi(2) values
      from 1.853 to 3.742, Z=3.342, P values above 0.05). There were statistically
      significant differences in age, depth of burn, total burn area, burn in lower
      limbs, infection of wound, venous transfusion of hypertonic solution and blood,
      femoral vein and subclavian vein catheterization, D-dimer, and bedridden duration
      after injury among patients between two groups (with chi(2) values from 4.569 to
      11.324, Z values respectively 7.357 and 7.012, P<0.05 or P<0.01). (3) Age, total
      burn area, burn in lower limbs, infection of wound, and D-dimer were the
      independent risk factors of DVT (with odds ratio respectively 2.904, 2.655,
      3.574, 2.786, 3.142, 95% confidence interval respectively 1.504-7.652, 1.368
      6.594, 1.958-8.511, 1.459-7.001, 1.922-8.062, P values below 0.05). CONCLUSIONS:
      The incidence of DVT in burn patients is relatively low; it is diagnosed after
      the 20th day post injury in most patients, and the overwhelming majority is the
      peripheral type. Age, total burn area, burn in lower limbs, infection of wound,
      and D-dimer are the independent risk factors of DVT in burn patients, with which
      its occurrence could be predicted.

PMID- 27030656
TI  - Mechanism for excitation-dependent photoluminescence from graphene quantum dots
      and other graphene oxide derivates: consensus, debates and challenges.
AB  - Luminescent nanomaterials, with wide applications in biosensing, bioimaging,
      illumination and display techniques, have been consistently garnering enormous
      research attention. In particular, those with wavelength-controllable emissions
      could be highly beneficial. Carbon nanostructures, including graphene quantum
      dots (GQDs) and other graphene oxide derivates (GODs), with excitation-dependent
      photoluminescence (PL), which means their fluorescence color could be tuned
      simply by changing the excitation wavelength, have attracted lots of interest.
      However the intrinsic mechanism for the excitation-dependent PL is still obscure
      and fiercely debated presently. In this review, we attempt to summarize the
      latest efforts to explore the mechanism, including the quantum confinement
      effect, surface traps model, giant red-edge effect, edge states model and
      electronegativity of heteroatom model, as well as the newly developed synergistic
      model, to seek some clues to unravel the mechanism. Meanwhile the controversial
      difficulties for each model are further discussed. Besides this, the challenges
      and potential influences of the synthetic methodology and development of the
      materials are illustrated extensively to elicit more thought and constructive
      attempts toward their application. 

PMID- 27030657
TI  - A Decade of Combination Antiretroviral Treatment in Asia: The TREAT Asia HIV
      Observational Database Cohort.
AB  - Asian countries have seen the expansion of combination antiretroviral therapy
      (cART) over the past decade. The TREAT Asia HIV Observational Database (TAHOD)
      was established in 2003 comprising 23 urban referral sites in 13 countries across
      the region. We examined trends in treatment outcomes in patients who initiated
      cART between 2003 and 2013. Time of cART initiation was grouped into three
      periods: 2003-2005, 2006-2009, and 2010-2013. We analyzed trends in undetectable
      viral load (VL; defined as VL <400 copies/ml), CD4 changes from pre-cART levels,
      and overall survival. Of 6,521 patients included, the overall median CD4 count at
      cART initiation was 120 cells/MUl (interquartile range: 38-218). Despite an
      increase over time, pre-cART CD4 counts remained <200 cells/MUl. Adjusted
      analyses showed undetectable VL was more likely when starting cART in later years
      [2006-2009: odds ratio (OR) = 1.76, 95% confidence interval (CI) (1.45, 2.15);
      and 2010-2013: OR = 3.04, 95% CI (2.33, 3.97), all p < .001, compared to 2003
      2005], and survival was improved [2006-2009: subdistribution hazard ratio (SHR) =
      0.41, 95% CI (0.27, 0.61), 2010-2013: SHR = 0.29, 95% CI (0.17, 0.49), all p <
      .001, compared to 2003-2005]. No differences in CD4 response was observed over
      time. Age and CD4 levels prior to cART initiation were associated with all three
      treatment outcomes, with older age and higher CD4 counts being associated with
      undetectable VL. Survival and VL response on cART have improved over the past
      decade in TAHOD, although CD4 count at cART initiation remained low. Greater
      effort should be made to facilitate earlier HIV diagnosis and linkage to care and
      treatment, to achieve greater improvements in treatment outcomes.

PMID- 27030658
TI  - Influence of a polarizable surrounding on the electronically excited states of
      aggregated perylene materials.
AB  - To tune the efficiency of organic semiconductor devices it is important to
      understand limiting factors as trapping mechanisms for excitons or charges. An
      understanding of such mechanisms deserves an accurate description of the involved
      electronical states in the given environment. In this study, we investigate how a
      polarizable surrounding influences the relative positions of electronically
      excited states of dimers of different perylene dyes. Polarization effects are
      particularly interesting for these systems, because gas phase computations
      predict that the CT states lie slightly above the corresponding Frenkel states. A
      polarizable environment may change this energy order because CT states are
      thought to be more sensitive to a polarizable surrounding than Frenkel states. A
      first insight we got via a TD-HF approach in combination with a polarizable
      continuum model (PCM). These give limited insights because TD-HF overestimates
      excitation energies of CT states. However, SCS-CC2 approaches, which are
      sufficiently accurate, cannot easily be used in combination with continuum
      solvent models. Hence, we developed two approaches to combine gas phase SCS-CC2
      results with solvent effects based on TD-HF computations. Their accuracies were
      finally checked via ADC(2)//COSMO computations. The results show that for
      perylene dyes a polarizable surrounding alone does not influence the energetic
      ordering of CT and Frenkel states. Variations in the energy order of the states
      only result from nuclear relaxation effects after the excitation process. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27030659
TI  - Diabetes prevention counseling is cost effective, US study finds.

PMID- 27030660
TI  - An ultra-low-voltage electronic implementation of inertial neuron model with
      nonmonotonous Liao's activation function.
AB  - The output of every neuron in neural network is specified by the employed
      activation function (AF) and therefore forms the heart of neural networks. As far
      as the design of artificial neural networks (ANNs) is concerned, hardware
      approach is preferred over software one because it promises the full utilization
      of the application potential of ANNs. Therefore, besides some arithmetic blocks,
      designing AF in hardware is the most important for designing ANN. While
      attempting to design the AF in hardware, the designs should be compatible with
      the modern Very Large Scale Integration (VLSI) design techniques. In this regard,
      the implemented designs should: only be in Metal Oxide Semiconductor (MOS)
      technology in order to be compatible with the digital designs, provide electronic
      tunability feature, and be able to operate at ultra-low voltage. Companding is
      one of the promising circuit design techniques for achieving these goals. In this
      paper, 0.5 V design of Liao's AF using sinh-domain technique is introduced.
      Furthermore, the function is tested by implementing inertial neuron model. The
      performance of the AF and inertial neuron model have been evaluated through
      simulation results, using the PSPICE software with the MOS transistor models
      provided by the 0.18-MUm Taiwan Semiconductor Manufacturer Complementary Metal
      Oxide Semiconductor (TSM CMOS) process. 

PMID- 27030661
TI  - Expectations of recovery: A prognostic factor in patients with neck pain
      undergoing manual therapy treatment.
AB  - BACKGROUND: Expectations have been investigated in populations seeking care for
      neck pain, however not considering potential confounding factors. The aim of this
      study was to investigate if pretreatment expectations of recovery is a prognostic
      factor for recovery from neck pain at 7 weeks follow-up in patients seeking
      manual therapy treatment. METHOD: The study was based on the Stockholm Manual
      Intervention Trial, a randomized controlled trial investigating efficiency of
      three combinations of manual therapy. The patients with neck pain were included
      in this study (n = 716). Expectations of recovery was measured at baseline; 'How
      likely is it, according to your judgment, that you are completely recovered from
      your neck/back problems in 7 weeks'. Patients answered on a 11-point scale,
      further categorized into low, moderate and high expectations. The outcome was
      measured at 7 weeks follow-up by a modified version of the Global Perceived
      Recovery Question. Potential effect measure modifiers and confounders were
      measured at baseline. Multivariable log binomial regression models were used to
      analyse the association between expectations and recovery, presented as relative
      risks and 95% confidence intervals (CI). RESULTS: High expectations of recovery
      yielded a 47% increased probability of being recovered at 7 weeks follow-up. High
      expectations of recovery yielded improved recovery in both men and women
      separately, but moderate expectations yielded improved recovery only among men.
      CONCLUSION: Our results suggest that expectations of recovery is a prognostic
      factor for recovery in patients with neck pain seeking manual therapy treatment.
      WHAT DOES THIS STUDY ADD?: We found that high expectations of recovery yielded a
      higher probability of recovery compared to having low expectations, also when
      considering potential confounding factors. Expectations seemed to have a more
      distinct influence on recovery among men.

PMID- 27030662
TI  - IDENTIFICATION AND HORMONE INDUCTION OF PUTATIVE CHITIN SYNTHASE GENES AND SPLICE
      VARIANTS IN Leptinotarsa decemlineata (SAY).
AB  - Chitin synthase (ChS) plays a critical role in chitin synthesis and excretion. In
      this study, two ChS genes (LdChSA and LdChSB) were identified in Leptinotarsa
      decemlineata. LdChSA contains two splicing variants, LdChSAa and LdChSAb. Within
      the first, second, and third larval instars, the mRNA levels of LdChSAa, LdChSAb,
      and LdChSB coincide with the peaks of circulating 20-hydroxyecdysone (20E) and
      juvenile hormone (JH). In vitro culture of midguts and an in vivo bioassay
      revealed that 20E and an ecdysteroid agonist halofenozide stimulated the
      expression of the three LdChSs. Conversely, a reduction of 20E by RNA
      interference (RNAi) of an ecdysteroidogenesis gene LdSHD repressed the expression
      of these LdChSs, and ingestion of halofenozide by LdSHD RNAi larvae rescued the
      repression. Moreover, disruption of 20E signaling by RNAi of LdEcR, LdE75, LdHR3,
      and LdFTZ-F1 reduced the expression levels of these genes. Similarly, in vitro
      culture and an in vivo bioassay showed that exogenous JH and a JH analog
      methoprene activated the expression of the three LdChSs, whereas a decrease in JH
      by RNAi of a JH biosynthesis gene LdJHAMT downregulated these LdChSs. It seems
      that JH upregulates LdChSs at the early stage of each instar, whereas a 20E pulse
      triggers the transcription of LdChSs during molting in L. decemlineata. 

PMID- 27030663
TI  - A High-Throughput Microfluidic Platform for Mammalian Cell Transfection and
      Culturing.
AB  - Mammalian synthetic biology could be augmented through the development of high
      throughput microfluidic systems that integrate cellular transfection, culturing,
      and imaging. We created a microfluidic chip that cultures cells and implements
      280 independent transfections at up to 99% efficiency. The chip can perform co
      transfections, in which the number of cells expressing each protein and the
      average protein expression level can be precisely tuned as a function of input
      DNA concentration and synthetic gene circuits can be optimized on chip. We co
      transfected four plasmids to test a histidine kinase signaling pathway and mapped
      the dose dependence of this network on the level of one of its constituents. The
      chip is readily integrated with high-content imaging, enabling the evaluation of
      cellular behavior and protein expression dynamics over time. These features make
      the transfection chip applicable to high-throughput mammalian protein and
      synthetic biology studies. 

PMID- 27030664
TI  - The role of the rectum in osmoregulation and the potential effect of renoguanylin
      on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta).
AB  - Teleosts living in seawater continually absorb water across the intestine to
      compensate for branchial water loss to the environment. The present study reveals
      that the Gulf toadfish (Opsanus beta) rectum plays a comparable role to the
      posterior intestine in ion and water absorption. However, the posterior intestine
      appears to rely more on SLC26a6 (a HCO3 (-)/Cl(-) antiporter) and the rectum
      appears to rely on NKCC2 (SLC12a1) for the purposes of solute-coupled water
      absorption. The present study also demonstrates that the rectum responds to
      renoguanylin (RGN), a member of the guanylin family of peptides that alters the
      normal osmoregulatory processes of the distal intestine, by inhibited water
      absorption. RGN decreases rectal water absorption more greatly than in the
      posterior intestine and leads to net Na(+) and Cl(-) secretion, and a reversal of
      the absorptive short-circuit current (ISC). It is hypothesized that maintaining a
      larger fluid volume within the distal segments of intestinal tract facilitates
      the removal of CaCO3 precipitates and other solids from the intestine. Indeed,
      the expression of the components of the Cl(-)-secretory response, apical CFTR,
      and basolateral NKCC1 (SLC12a2), are upregulated in the rectum of the Gulf
      toadfish after 96 h in 60 ppt, an exposure that increases CaCO3 precipitate
      formation relative to 35 ppt. Moreover, the downstream intracellular effects of
      RGN appear to directly inhibit ion absorption by NKCC2 and anion exchange by
      SLC26a6. Overall, the present findings elucidate key electrophysiological
      differences between the posterior intestine and rectum of Gulf toadfish and the
      potent regulatory role renoguanylin plays in osmoregulation.

PMID- 27030666
TI  - Brown adipose tissue is involved in the seasonal variation of cold-induced
      thermogenesis in humans.
AB  - Brown adipose tissue (BAT) contributes to whole-body energy expenditure (EE),
      especially cold-induced thermogenesis (CIT), in humans. Although it is known that
      EE and CIT vary seasonally, their relationship with BAT has not been
      investigated. In the present study, we examined the impact of BAT on seasonal
      variations of EE/CIT and thermal responses to cold exposure in a randomized
      crossover design. Forty-five healthy male volunteers participated, and their BAT
      was assessed by positron emission tomography and computed tomography. CIT, the
      difference of EE at 27oC and after 2-h cold exposure at 19oC, significantly
      increased in winter compared to summer, being greater in subjects with
      metabolically active BAT (High BAT, 185.6 kcal/d, 18.3 kcal/d, P<0.001) than
      those without (Low BAT, 90.6 kcal/d, -46.5 kcal/d, P<0.05). Multivariate
      regression analysis revealed a significant interaction effect between season and
      BAT on CIT (P<0.001). The cold-induced drop of tympanic temperature (Tty) and
      skin temperature (Tskin) in the forehead region and in the supraclavicular region
      close to BAT deposits were smaller in the High BAT group than in the Low BAT
      group in winter but not in summer. In contrast, the drop of Tskinin the
      subclavicular and peripheral regions distant from BAT was similar in the two
      groups in both seasons. In conclusion, CIT increased from summer to winter in a
      BAT-dependent manner, paralleling cold-induced changes in Tty/Tskin, indicating a
      role of BAT in seasonal changes in the thermogenic and thermal responses to cold
      exposure in humans.

PMID- 27030665
TI  - Rapid-onset hypoglycemia suppresses Fos expression in discrete parts of the
      ventromedial nucleus of the hypothalamus.
AB  - The consensus view of the ventromedial nucleus of the hypothalamus (VMH) is that
      it is a key node in the rodent brain network controlling sympathoadrenal
      counterregulatory responses to hypoglycemia. To identify the location of
      hypoglycemia-responsive neurons in the VMH, we performed a high spatial
      resolution Fos analysis in the VMH of rats made hypoglycemic with intraperitoneal
      injections of insulin. We examined Fos expression in the four constituent parts
      of VMH throughout its rostrocaudal extent and determined their relationship to
      blood glucose concentrations. Hypoglycemia significantly decreased Fos expression
      only in the dorsomedial and central parts of the VMH, but not its anterior or
      ventrolateral parts. Moreover, the number of Fos-expressing neurons was
      significantly and positively correlated in the two responsive regions with
      terminal blood glucose concentrations. We also measured Fos responses in the
      paraventricular nucleus of the hypothalamus (PVH) and in several levels of the
      periaqueductal gray (PAG), which receives strong projections from the VMH. We
      found the expected and highly significant increase in Fos in the neuroendocrine
      PVH, which was negatively correlated to terminal blood glucose concentrations,
      but no significant differences were seen in any part of the PAG. Our results show
      that there are distinct populations of VMH neurons whose Fos expression is
      suppressed by hypoglycemia, and their numbers correlate with blood glucose. These
      findings support a clear division of glycemic control functions within the
      different parts of the VMH.

PMID- 27030667
TI  - Comparison of compensatory reserve during lower-body negative pressure and
      hemorrhage in nonhuman primates.
AB  - Compensatory reserve was measured in baboons (n = 13) during hemorrhage (Hem) and
      lower-body negative pressure (LBNP) using a machine-learning algorithm developed
      to estimate compensatory reserve by detecting reductions in central blood volume
      during LBNP. The algorithm calculates compensatory reserve index (CRI) from
      normovolemia (CRI = 1) to cardiovascular decompensation (CRI = 0). The hypothesis
      was that Hem and LBNP will elicit similar CRI values and that CRI would have
      higher specificity than stroke volume (SV) in predicting decompensation. Blood
      was removed in four steps: 6.25%, 12.5%, 18.75%, and 25% of total blood volume.
      Four weeks after Hem, the same animals were subjected to four levels of LBNP that
      was matched on the basis of their central venous pressure. Data (mean +/- 95%
      confidence interval) indicate that CRI decreased (P < 0.001) from baseline during
      Hem (0.69 +/- 0.10, 0.57 +/- 0.09, 0.36 +/- 0.10, 0.16 +/- 0.08, and 0.08 +/-
      0.03) and LBNP (0.76 +/- 0.05, 0.66 +/- 0.08, 0.36 +/- 0.13, 0.23 +/- 0.11, and
      0.14 +/- 0.09). CRI was not different between Hem and LBNP (P = 0.20). Linear
      regression analysis between Hem CRI and LBNP CRI revealed a slope of 1.03 and a
      correlation coefficient of 0.96. CRI exhibited greater specificity than SV in
      both Hem (92.3 vs. 82.1) and LBNP (94.8 vs. 83.1) and greater ROC AUC in Hem
      (0.94 vs. 0.84) and LBNP (0.94 vs. 0.92). These data support the hypothesis that
      Hem and LBNP elicited the same CRI response, suggesting that measurement of
      compensatory reserve is superior to SV as a predictor of cardiovascular
      decompensation.

PMID- 27030668
TI  - Obesity-prone high-fat-fed rats reduce caloric intake and adiposity and gain more
      fat-free mass when allowed to self-select protein from carbohydrate:fat intake.
AB  - We tested the hypothesis that, for rats fed a high-fat diet (HFD), a
      prioritization of maintaining protein intake may increase energy consumption and
      hence result in obesity, particularly for individuals prone to obesity ("fat
      sensitive," FS, vs. "fat resistant," FR). Male Wistar rats (n = 80) first
      received 3 wk of HFD (protein 15%, fat 42%, carbohydrate 42%), under which they
      were characterized as being FS (n = 18) or FR (n = 20) based on body weight gain.
      They then continued on the same HFD but in which protein (100%) was available
      separately from the carbohydrate:fat (50:50%) mixture. Under this second regimen,
      all rats maintained their previous protein intake, whereas intake of fat and
      carbohydrate was reduced by 50%. This increased protein intake to 26% and
      decreased fat intake to 37%. Adiposity gain was prevented in both FR and FS rats,
      and gain in fat-free mass was increased only in FS rats. At the end of the study,
      the rats were killed 2 h after ingestion of a protein meal, and their tissues and
      organs were collected for analysis of body composition and measurement of mRNA
      levels in the liver, adipose tissue, arcuate nucleus, and nucleus accumbens. FS
      rats had a higher expression of genes encoding enzymes involved in lipogenesis in
      the liver and white adipose tissue. These results show that FS rats strongly
      reduced food intake and adiposity gain through macronutrient selection, despite
      maintenance of a relatively high-fat intake and overexpression of genes favoring
      lipogenesis.

PMID- 27030670
TI  - Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize
      newly synthesized Cox1.
AB  - The mitochondrial cytochrome c oxidase assembles in the inner membrane from
      subunits of dual genetic origin. The assembly process of the enzyme is initiated
      by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex
      maturation, transient assembly intermediates, consisting of structural subunits
      and specialized chaperone-like assembly factors, are formed. In addition,
      cofactors such as heme and copper have to be inserted into the nascent complex.
      To regulate the assembly process, the availability of Cox1 is under control of a
      regulatory feedback cycle in which translation of COX1 mRNA is stalled when
      assembly intermediates of Cox1 accumulate through inactivation of the
      translational activator Mss51. Here we isolate a cytochrome c oxidase assembly
      intermediate in preparatory scale from coa1Delta mutant cells, using Mss51 as
      bait. We demonstrate that at this stage of assembly, the complex has not yet
      incorporated the heme a cofactors. Using quantitative mass spectrometry, we
      define the protein composition of the assembly intermediate and unexpectedly
      identify the putative methyltransferase Oms1 as a constituent. Our analyses show
      that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly
      synthesized Cox1.

PMID- 27030669
TI  - GLP-1 and weight loss: unraveling the diverse neural circuitry.
AB  - Glucagon-like peptide-1 (GLP-1) is currently one of the most promising biological
      systems for the development of effective obesity pharmacotherapies. Long-acting
      GLP-1 analogs potently reduce food intake and body weight, and recent discoveries
      reveal that peripheral administration of these drugs reduces food intake largely
      through humoral pathways involving direct action on brain GLP-1 receptors (GLP
      1R). Thus, it is of critical importance to understand the neural systems through
      which GLP-1 and long-acting GLP-1 analogs reduce food intake and body weight. In
      this review, we discuss several neural, physiological, cellular and molecular, as
      well as behavioral mechanisms through which peripheral and central GLP-1R
      signaling reduces feeding. Particular attention is devoted to discussion
      regarding the numerous neural substrates through which GLP-1 and GLP-1 analogs
      act to reduce food intake and body weight, including various hypothalamic nuclei
      (arcuate nucleus of the hypothalamus, periventricular hypothalamus, lateral
      hypothalamic area), hindbrain nuclei (parabrachial nucleus, medial nucleus
      tractus solitarius), hippocampus (ventral subregion; vHP), and nuclei embedded
      within the mesolimbic reward circuitry [ventral tegmental area (VTA) and nucleus
      accumbens (NAc)]. In some of these nuclei [VTA, NAc, and vHP], GLP-1R activation
      reduces food intake and body weight without concomitant nausea responses,
      suggesting that targeting these specific pathways may be of particular interest
      for future obesity pharmacotherapy. The widely distributed neural systems through
      which GLP-1 and GLP-1 analogs act to reduce body weight highlight the complexity
      of the neural systems regulating energy balance, as well as the challenges for
      developing effective obesity pharmacotherapies that reduce feeding without
      producing parallel negative side effects.

PMID- 27030671
TI  - An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable
      microtubules in migrating cells.
AB  - Multiple formins regulate microtubule (MT) arrays, but whether they function
      individually or in a common pathway is unknown. Lysophosphatidic acid (LPA)
      stimulates the formation of stabilized detyrosinated MTs (Glu MTs) in NIH3T3
      fibroblasts through RhoA and the formin mDia1. Here we show that another formin,
      INF2, is necessary for mDia1-mediated induction of Glu MTs and regulation of MT
      dynamics and that mDia1 can be bypassed by activating INF2. INF2 localized to MTs
      after LPA treatment in an mDia1-dependent manner, suggesting that mDia1 regulates
      INF2. Mutants of either formin that disrupt their interaction failed to rescue MT
      stability in cells depleted of the respective formin, and the mDia1-interacting
      protein IQGAP1 regulated INF2's localization to MTs and the induction of Glu MTs
      by either formin. The N-terminus of IQGAP1 associated with the C-terminus of INF2
      directly, suggesting the possibility of a tripartite complex stimulated by LPA.
      Supporting this, the interaction of mDia1 and INF2 was induced by LPA and
      dependent on IQGAP1. Our data highlight a unique mechanism of formin action in
      which mDia1 and INF2 function in series to stabilize MTs and point to IQGAP1 as a
      scaffold that facilitates the activation of one formin by another.

PMID- 27030672
TI  - The Grp170 nucleotide exchange factor executes a key role during ERAD of cellular
      misfolded clients.
AB  - When a protein misfolds in the endoplasmic reticulum (ER), it retrotranslocates
      to the cytosol and is degraded by the proteasome via a pathway called ER
      associated degradation (ERAD). To initiate ERAD, ADP-BiP is often recruited to
      the misfolded client, rendering it soluble and translocation competent. How the
      misfolded client is subsequently released from BiP so that it undergoes
      retrotranslocation, however, remains enigmatic. Here we demonstrate that the ER
      resident nucleotide exchange factor (NEF) Grp170 plays an important role during
      ERAD of the misfolded glycosylated client null Hong Kong (NHK). As a NEF, Grp170
      triggers nucleotide exchange of BiP to generate ATP-BiP. ATP-BiP disengages from
      NHK, enabling it to retrotranslocate to the cytosol. We demonstrate that Grp170
      binds to Sel1L, an adapter of the transmembrane Hrd1 E3 ubiquitin ligase
      postulated to be the retrotranslocon, and links this interaction to Grp170's
      function during ERAD. More broadly, Grp170 also promotes degradation of the
      nonglycosylated transthyretin (TTR) D18G misfolded client. Our findings thus
      establish a general function of Grp170 during ERAD and suggest that positioning
      this client-release factor at the retrotranslocation site may afford a mechanism
      to couple client release from BiP and retrotranslocation.

PMID- 27030673
TI  - Overexpression of Sly41 suppresses COPII vesicle-tethering deficiencies by
      elevating intracellular calcium levels.
AB  - SLY41 was identified as a multicopy suppressor of loss of Ypt1, a Rab GTPase
      essential for COPII vesicle tethering at the Golgi complex. SLY41 encodes a
      polytopic membrane protein with homology to a class of solute transporter
      proteins, but how overexpression suppresses vesicle-tethering deficiencies is not
      known. Here we show that Sly41 is efficiently packaged into COPII vesicles and
      actively cycles between the ER and Golgi compartments. SLY41 displays synthetic
      negative genetic interactions with PMR1, which encodes the major Golgi-localized
      Ca(2+)/Mn(2+) transporter and suggests that Sly41 influences cellular Ca(2+) and
      Mn(2+) homeostasis. Experiments using the calcium probe aequorin to measure
      intracellular Ca(2+) concentrations in live cells reveal that Sly41
      overexpression significantly increases cytosolic calcium levels. Although
      specific substrates of the Sly41 transporter were not identified, our findings
      indicate that localized overexpression of Sly41 to the early secretory pathway
      elevates cytosolic calcium levels to suppress vesicle-tethering mutants. In vitro
      SNARE cross-linking assays were used to directly monitor the influence of Ca(2+)
      on tethering and fusion of COPII vesicles with Golgi membranes. Strikingly,
      calcium at suppressive concentrations stimulated SNARE-dependent membrane fusion
      when vesicle-tethering activity was reduced. These results show that calcium
      positively regulates the SNARE-dependent fusion stage of ER-Golgi transport.

PMID- 27030674
TI  - Staufen1 impairs stress granule formation in skeletal muscle cells from myotonic
      dystrophy type 1 patients.
AB  - Myotonic dystrophy (DM1) is caused by an expansion of CUG repeats (CUG(exp)) in
      the DMPK mRNA 3'UTR. CUG(exp)-containing mRNAs become toxic to cells by
      misregulating RNA-binding proteins. Here we investigated the consequence of this
      RNA toxicity on the cellular stress response. We report that cell stress
      efficiently triggers formation of stress granules (SGs) in proliferating,
      quiescent, and differentiated muscle cells, as shown by the appearance of
      distinct cytoplasmic TIA-1- and DDX3-containing foci. We show that Staufen1 is
      also dynamically recruited into these granules. Moreover, we discovered that DM1
      myoblasts fail to properly form SGs in response to arsenite. This blockage was
      not observed in DM1 fibroblasts, demonstrating a cell type-specific defect. DM1
      myoblasts display increased expression and sequestration of toxic CUG(exp) mRNAs
      compared with fibroblasts. Of importance, down-regulation of Staufen1 in DM1
      myoblasts rescues SG formation. Together our data show that Staufen1 participates
      in the inhibition of SG formation in DM1 myoblasts. These results reveal that DM1
      muscle cells fail to properly respond to stress, thereby likely contributing to
      the complex pathogenesis of DM1.

PMID- 27030676
TI  - New probabilistic risk assessment of ethylhexyl methoxycinnamate: Comparing the
      genotoxic effects of trans- and cis-EHMC.
AB  - Ethylhexyl methoxycinnamate (EHMC) is a widely used UV filter present in a large
      number of personal care products (PCPs). Under normal conditions, EHMC occurs in
      a mixture of two isomers: trans-EHMC and cis-EHMC in a ratio of 99:1. When
      exposed to sunlight, the trans isomer is transformed to the less stable cis
      isomer and the efficiency of the UV filter is reduced. To date, the toxicological
      effects of the cis-EHMC isomer remain largely unknown. We developed a completely
      new method for preparing cis-EHMC. An EHMC technical mixture was irradiated using
      a UV lamp and 98% pure cis-EHMC was isolated from the irradiated solution using
      column chromatography. The genotoxic effects of the isolated cis-EHMC isomer and
      the nonirradiated trans-EHMC were subsequently measured using two bioassays (SOS
      chromotest and UmuC test). In the case of trans-EHMC, significant genotoxicity
      was observed using both bioassays at the highest concentrations (0.5 - 4 mg mL-1
      ). In the case of cis-EHMC, significant genotoxicity was only detected using the
      UmuC test at concentrations of 0.25 - 1 mg mL-1 . Based on these results, the
      NOEC was calculated for both cis- and trans-EHMC, 0.038 and 0.064 mg mL-1 ,
      respectively. Risk assessment of dermal, oral and inhalation exposure to PCPs
      containing EHMC was carried out for a female population using probabilistic
      simulation and by using Quantitative in vitro to in vivo extrapolation (QIVIVE).
      The risk of cis-EHMC was found to be ~1.7 times greater than trans-EHMC. In the
      case of cis-EHMC, a hazard index of 1 was exceeded in the 92nd percentile. Based
      on the observed differences between the isomers, EHMC application in PCPs
      requires detailed reassessment. Further exploration of the toxicological effects
      and properties of cis-EHMC is needed in order to correctly predict risks posed to
      humans and the environment. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32:
      569-580, 2017.

PMID- 27030677
TI  - Outcome of incidentally detected airway nodules.
AB  - Low-dose chest computed tomography (LDCT) screening increased detection of airway
      nodules. Most nodules appear to be secretions, but pathological lesions may show
      similar findings. The National Comprehensive Cancer Network (NCCN) recommends
      repeating LDCT after 1 month and proceeding to bronchoscopy if the nodules
      persist. However, no reports exist about incidentally detected airway nodules. We
      investigated the significance of airway nodules detected by LDCT screening.We
      screened patients with incidental airway nodules detected by LDCT in the Seoul
      National University Hospital group. The characteristics of computed tomography,
      bronchoscopy, pathology and clinical findings were analysed.Among 53 036
      individuals who underwent LDCT screening, 313 (0.6%) had airway nodules. Of
      these, 186 (59.4%) were followed-up with chest computed tomography and/or
      bronchoscopy. Seven (3.8%) cases had significant lesions, including leiomyoma
      (n=2), endobronchial tuberculosis (n=2), chronic inflammation (n=1), hamartoma
      (n=1) and benign granuloma (n=1). The remaining 179 lesions were transient,
      suggesting that they were secretions.The use of LDCT for lung cancer screening
      demonstrated the low incidence of airway lesions. Most lesions were transient
      secretions. True pathological lesions were rare, and no malignant lesion was
      found. The current recommendation of the NCCN guideline is a reasonable approach
      that can avoid unnecessary bronchoscopy.

PMID- 27030678
TI  - Prevalence of and treatment outcomes for patients with obstructive sleep apnoea
      identified by preoperative screening compared with clinician referrals.
AB  - Obstructive sleep apnoea (OSA) has implications perioperatively. We compared the
      prevalence of OSA and outcome with continuous positive airway pressure (CPAP) in
      patients diagnosed through preoperative screening and following referrals from
      other clinicians.Among 1412 patients (62% males) the prevalence of OSA, Epworth
      Sleepiness Score (ESS), the number referred for CPAP, and short and longer term
      use of CPAP were compared between the two groups.The prevalence of OSA was
      similar (62% versus 58%). There were differences in mean+/-sd age (61+/-16 versus
      55+/-13 years; p<0.0001), ESS (11+/-6 versus 8+/-5; p<0.0001) and oxygen
      desaturation index (22+/-20 versus 19+/-17; p=0.039). Clinician-referred patients
      were more likely to be offered CPAP (p<0.0001; OR 2.84). Pre-assessment patients
      with mild OSA were less likely to continue CPAP long term (p=0.002; OR 6.8). No
      difference was seen between moderate and severe OSA patients.The prevalence of
      OSA was similar in both groups but pre-assessment patients were younger and less
      symptomatic. Preoperative screening of patients is worthwhile, independent of any
      effect of CPAP upon surgical outcomes; younger and less symptomatic patients are
      identified earlier. Pre-assessment patients with mild OSA were less likely to use
      CPAP; this should be considered when offering CPAP to these patients prior to
      surgery.

PMID- 27030675
TI  - New and emerging targeted therapies for cystic fibrosis.
AB  - Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects
      about 70,000 people worldwide. The clinical manifestations of the disease are
      caused by defects in the cystic fibrosis transmembrane conductance regulator
      (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated
      understanding of how thousands of mutations in the CFTR gene affect the structure
      and function of the CFTR protein. Much progress has been made over the past
      decade with the development of orally bioavailable small molecule drugs that
      target defective CFTR proteins caused by specific mutations. Furthermore, there
      is considerable optimism about the prospect of gene replacement or editing
      therapies to correct all mutations in cystic fibrosis. The recent approvals of
      ivacaftor and lumacaftor represent the genesis of a new era of precision medicine
      in the treatment of this condition. These drugs are having a positive impact on
      the lives of people with cystic fibrosis and are potentially disease modifying.
      This review provides an update on advances in our understanding of the structure
      and function of the CFTR, with a focus on state of the art targeted drugs that
      are in development.

PMID- 27030679
TI  - Inequalities in lung cancer: a world of EGFR.
AB  - Epidermal growth factor receptor gene (EGFR) mutation status has emerged as a
      crucial issue in lung cancer management. Availability and cost of tests and
      tyrosine kinase inhibitors (TKIs) may vary as a function of country
      development.We conducted a prospective specialist opinion survey to map EGFR test
      and EGFR-TKI availability and detect associations with the Human Development
      Index (HDI). A questionnaire was sent to specialists in thoracic oncology in all
      United Nations Member States.We obtained responses from 74 countries, comprising
      78% of the worldwide population. Nonresponding countries had significantly lower
      HDI rank than responding countries. EGFR mutation analysis was routinely
      available in 57 countries (70% of the worldwide population). The cost of the test
      was <US$500 in 49 countries (42.5% of the worldwide population). Test
      availability and cost were both significantly linked to HDI. Erlotinib,
      gefitinib, afatinib and icotinib were routinely available in 75%, 66%, 31% and
      23% of the worldwide population, respectively, also associated with HDI.EGFR
      mutation testing and EGFR-TKIs are widely accessible in routine practice
      worldwide. However, there are large discrepancies in access to this innovative
      treatment path and in its cost for patients as a function of country development.

PMID- 27030680
TI  - Diagnostic concordance of different criteria for exercise pulmonary hypertension
      in subjects with normal resting pulmonary artery pressure.

PMID- 27030682
TI  - Segmental transition of the first syllables of words in Japanese children who
      stutter: Comparison between word and sentence production.
AB  - Matsumoto-Shimamori, Ito, Fukuda, & Fukuda (2011) proposed the hypothesis that in
      Japanese, the transition from the core vowels (i.e. syllable nucleus) of the
      first syllables of words to the following segments affected the occurrence of
      stuttering. Moreover, in this transition position, an inter-syllabic transition
      precipitated more stuttering than an intra-syllabic one (Shimamori & Ito, 2007,
      2008). However, these studies have only used word production tasks. The purpose
      of this study was to investigate whether the same results could be obtained in
      sentence production tasks. Participants were 28 Japanese school-age children who
      stutter, ranging in age from 7;3 to 12;7. The frequency of stuttering on words
      with an inter-syllabic transition was significantly higher than on those having
      an intra-syllabic transition, not only in isolated words but in the first words
      of sentences. These results suggested that Matsumoto et al.'s hypothesis could be
      applicable to the results of sentence production tasks.

PMID- 27030681
TI  - "Scar-cinoma": viewing the fibrotic lung mesenchymal cell in the context of
      cancer biology.
AB  - Lung cancer and pulmonary fibrosis are common, yet distinct, pathological
      processes that represent urgent unmet medical needs. Striking clinical and
      mechanistic parallels exist between these distinct disease entities. The goal of
      this article is to examine lung fibrosis from the perspective of cancer
      associated phenotypic hallmarks, to discuss areas of mechanistic overlap and
      distinction, and to highlight profibrotic mechanisms that contribute to
      carcinogenesis. Ultimately, we speculate that such comparisons might identify
      opportunities to leverage our current understanding of the pathobiology of each
      disease process in order to advance novel therapeutic approaches for both. We
      anticipate that such "outside the box" concepts could be translated to a more
      precise and individualised approach to fibrotic diseases of the lung.

PMID- 27030683
TI  - Predictors of early graft failure after coronary artery bypass grafting for
      chronic total occlusion.
AB  - OBJECTIVES: Little is known regarding the transit-time flow measurement (TTFM)
      variables in grafts anastomosed to chronically totally occluded vessels (CTOs).
      We aimed to establish the TTFM cut-off values for detecting graft failure in
      bypass grafts anastomosed to chronically totally occluded arteries and clarify
      the relationship between early graft failure and the grade of collateral
      circulation/regional wall motion of the CTO territory. METHODS: Among 491
      patients who underwent isolated coronary artery bypass grafting (CABG) from 2009
      to 2015, 196 cases with CTOs underwent postoperative coronary angiography within
      1 month after CABG. Two hundred and forty-one CTOs in all patients were examined.
      Thirty-two CTOs (13%) were not bypassed and 214 conduits were anastomosed to CTOs
      and underwent intraoperative TTFM. Arterial conduits and saphenous vein grafts
      (SVGs) were used in 102 and 112 cases, respectively. Among the arterial conduit
      procedures that were performed, 78 involved the left internal thoracic artery
      (LITA), 10 involved the right internal thoracic artery (RITA) and 14 involved the
      right gastroepiploic artery (rGEA). Any graft showing Fitzgibbon type B or O
      lesions on angiography was considered to be a failing graft. RESULTS: The
      insufficiency rates for LITA, RITA, rGEA and SVG procedures were 5.1, 10, 14.3
      and 7.1%, respectively. The TTFM variables recorded in failing grafts had a
      significantly lower mean flow (Qmean) and higher pulsatility index (PI) compared
      with patent grafts. Furthermore, akinetic or dyskinetic wall motion in the
      territory of bypassed CTOs was observed at a significantly higher rate in failing
      grafts. A multivariable regression analysis and receiver operating characteristic
      analysis revealed good predictors of early graft failure as follows: a Qmean
      value of < 11.5 ml/min for arterial conduits, a PI value of >5.85 and
      akinetic/dyskinetic wall motion in the CTO territory for SVGs. The Rentrop
      collateral grade was not associated with early graft failure. CONCLUSIONS: The
      Qmean value and PI value by the TTFM are useful to detect early graft failure in
      conduits anastomosed to CTOs. The collateral grade is not associated with graft
      failure; however, bypass grafting to CTOs with akinetic/dyskinetic wall motion
      should be carefully considered.

PMID- 27030684
TI  - A novel and simple method for identifying the lung intersegmental plane using
      thermography.
AB  - Identifying the intersegmental plane is very important for successful lung
      segmentectomy. Although several methods are available, they require specialized
      skills and pose a potential risk of losing sight of the correct intersegmental
      planes. Therefore, easier and more reliable methods are required. In this study,
      we hypothesized that surface temperatures of resecting segments or lobes decrease
      because of blood flow suppression after the ligation of target arteries and
      veins, and intersegmental planes can be visualized using a thermography. To test
      this hypothesis, we performed six lung resections (two lobectomies and four
      segmentectomies) on three pigs and, using a handheld thermography, we monitored
      the lung surface temperatures to identify intersegmental planes. We demonstrated
      that thermal imaging sharply demarcated intersegmental planes soon after the
      ligation of vessels in all procedures. Compared with other methods, thermography
      requires no special technical skills, drug injection and lung inflation.
      Therefore, we believe that the thermographic method described in this study will
      be a powerful option to identify intersegmental planes during anatomical lung
      segmentectomy.

PMID- 27030685
TI  - Role of extracorporeal life support after pulmonary endarterectomy: a single
      centre experience.
AB  - OBJECTIVES: Extracorporeal life support (ECLS) for rescue after pulmonary
      endarterectomy (PEA) has become a viable option. This study aims to present a
      single-centre experience looking at the indications and outcome of ECLS after
      PEA. METHODS: Retrospective analysis of all patients undergoing PEA from January
      2008 to January 2015 in our institution. RESULTS: Among 144 consecutive patients
      undergoing PEA for chronic thromboembolic pulmonary hypertension, 6 (4%) received
      ECLS postoperatively for right ventricular (RV) failure (n = 3), severe
      hypoxaemia (n = 2) and haemorrhagic pulmonary oedema (n = 1). ECLS configuration
      was central veno-arterial (cVA) in 3 patients, peripheral VA (pVA) in 1 and veno
      venous (VV) in 2. One patient with cVA was switched to VV after 5 days. Overall
      ECLS duration ranged between 3 and 39 (median 5) days. ECLS patients had higher
      preoperative total pulmonary vascular resistance (TPR) compared with non-ECLS
      patients (1477 +/- 671 vs 954 +/- 462 Dynes.s.cm(-5), P = 0.009) and more
      frequently required hospital admission for RV failure before surgery (50 vs 9%, P
      = 0.02). The overall in-hospital mortality rate for all patients was 2% (3/144),
      including one ECLS patient on pVA. The remaining 5 ECLS patients (83%) were
      discharged from the hospital and are alive after a median follow-up of 11 (range
      6-27) months. Two ECLS patients (40%) are on therapy for residual PH compared
      with 13 (10%) in the non-ECLS patients (P = 0.09). CONCLUSIONS: ECLS is a safe
      and important rescue option after PEA. The use of ECLS may expand eligibility for
      PEA by allowing sicker patients to undergo surgery.

PMID- 27030686
TI  - The functional status of neoaortic valve and left ventricular outlet tract after
      arterial switch operation for transposition of great arteries with left
      ventricular outlet tract obstruction.
AB  - OBJECTIVES: To assess the function of the left ventricular outlet tract and
      neoaortic valve after arterial switch operation for patients with transposition
      of the great arteries and left ventricular outlet tract obstruction. METHODS: The
      data of 40 patients, who underwent arterial switch surgery with transposition of
      the great arteries with left ventricular outlet tract obstruction and a
      concomitant left ventricular outlet tract obstruction relieving procedure, were
      retrospectively analysed. Ultrasonic cardiogram and intraoperative findings,
      surgical methods and early and follow-up results were also summarized. RESULTS:
      Early death occurred in one case. One patient died in follow-up stage and 3
      patients were lost during follow-up. In all the 35 patients accepting follow-up,
      1 patient had a reoccurring left ventricular outlet tract obstruction, 1 patient
      had mild neoaortic stenosis, whereas mild and moderate neoaortic regurgitation
      occurred in 11 and 2 patients, respectively. The median pressure gradient across
      the left ventricular outlet tract was 6.8 mmHg (range: 2-49 mmHg) during follow
      up which was statistically significant compared with that before surgery. We
      defined death, reintervention and rehospitalization for cardiac reasons as a
      cardiac event; the survival rate of being free from cardiac event for 1 year and
      5 years was 92.8 +/- 0.04%, respectively. CONCLUSIONS: Anatomical features and
      pressure gradient should be used together to evaluate the severity of
      obstruction, whereas the mid-term outcomes can be satisfied after arterial switch
      operation for the appropriate candidates.

PMID- 27030687
TI  - Enhancing the Safe and Effective Management of Chronic Pain in Accountable Care
      Organization Primary Care Practices in Kentucky.
AB  - Chronic pain is a prevalent chronic condition with significant burden and
      economic impact in the United States. Chronic pain is particularly abundant in
      primary care, with an estimated 52% of chronic pain patients obtaining care from
      primary care physicians (PCPs). However, PCPs often lack adequate training and
      have limited time and resources to effectively manage chronic pain. Chronic pain
      management is complex in nature because of high co-occurrence of psychiatric
      disorders and other medical comorbidities in patients. This article describes a
      quality improvement initiative conducted by the American College of Physicians
      (ACP), in collaboration with the Kentucky ACP Chapter, and the Center for Health
      Services and Outcomes Research at the Johns Hopkins Bloomberg School of Public
      Health, to enhance chronic pain management in 8 primary care practices
      participating in Accountable Care Organizations in Kentucky, with a goal of
      enhancing the screening, diagnosis, and treatment of patients with chronic pain.

PMID- 27030688
TI  - Measuring Quality in Cancer Care: A Critical Need for Clinician Engagement.

PMID- 27030689
TI  - Heart Failure Readmission Reduction.
AB  - Little is known regarding effectiveness of readmission reduction programs over
      time. The Heart Failure Management Program (HFMP) of St. John's Physician Group
      Practice (PGP) Demonstration provided an opportunity to assess outcomes over an
      extended period. Data from an electronic health record, an inpatient database, a
      disease registry, and the Social Security Death Master File were analyzed for
      patients admitted with heart failure (HF) for 5 years before (Period 1) and 5
      years after (Period 2) inception of PGP. HF admissions decreased (Period 1,
      58.3/month; Period 2, 52.4/month, P = .007). Thirty-day all-cause readmission
      rate dropped from Period 1 (annual average 18.8% [668/3545]) to year 1 of Period
      2 (16.9% [136/804], P = .04) and remained stable thereafter (annual average 16.8%
      [589/3503]). Thirty-day mortality rate was flat throughout. HFMP was associated
      with decreased readmissions, primarily related to outpatient case management,
      while mortality remained stable.

PMID- 27030690
TI  - Diagnostic Delays and Errors in Head and Neck Cancer Patients: Opportunities for
      Improvement.
AB  - A retrospective review of 100 sequential patients (2009-2012) with head and neck
      cancer was performed to determine the frequency of 5 types of diagnostic delays
      and errors outlined by the Institute of Medicine. There were a total of 105
      diagnostic delays/errors. The most common was delay in being seen in the
      otolaryngology clinic after referral placement (28.6%), followed by diagnostic
      error by the referring physician (22%), delay in referral of a symptomatic
      patient to the otolaryngology clinic (16.2%), delay in employing an appropriate
      diagnostic test or procedure (15.2%), delay in action following reporting of
      pathology or imaging results for an incidental lesion (11.4%), diagnostic error
      by the otolaryngology clinic (2.8%), delay in action following reporting of
      pathology or imaging results for the symptomatic lesion (2.8%), and use of
      outmoded tests or therapy (1%). Increased awareness of these types of
      delays/errors will direct actions and processes to reduce or eliminate them.

PMID- 27030691
TI  - The role of metabolic state and obestatin in control of chicken ovarian hormone
      release.
AB  - The aim of the present study was to examine the role and interrelationships
      between calorie restriction and obestatin in the control of hormone release by
      chicken ovarian tissue. For this purpose, we compared the release of progesterone
      (P), testosteron (T), estradiol (E), and arginine-vasotocin (AVT) by ovarian
      fragments isolated from chicken subjected and not subjested to food restriction,
      as well as the response of these ovarian fragments to obestatin additions.It was
      observed that food restriction promoted release of P, reduced output of T, but
      did not affect basal E and AVT release. Obestatin addition reduced E, promoted
      AVT, and did not alter P and T release by ovarian tissue isolated from ad libitum
      fed chicken. In ovarian fragments of fasted hens it reduced E, promoted T, and
      did not influence P and AVT release.The present observations demonstrate (1) that
      obestatin can directly control the release of avian ovarian hormones - regulators
      of reproduction, (2) that metabolic state can control the release of these
      hormones, and (3) metabolic state can alter the response of ovarian hormones to
      obestatin. 

PMID- 27030692
TI  - The level and source of free-methionine affect body composition and breast muscle
      traits in growing broilers.
AB  - Although dietary Met, as the first limiting amino acid (AA), has been extensively
      studied for poultry, little is known about how the supply and source of free Met
      affect tissue composition. The purpose of this study was to investigate the
      effect of feeding young broiler chickens with a deficient or sufficient TSAA
      (Met+Cys) supply, using either dl-Met (dl-Met+ and dl-Met-, for respectively
      diets sufficient and deficient in TSAA) or dl-2-hydroxy-4-methylthiobutyric acid
      (HMTBA+ and HMTBA-, for respectively diets sufficient and deficient in TSAA) as a
      Met source on tissue composition and breast muscle traits. For both Met sources,
      the deficient diets were formulated to provide true digestible Met:Lys and
      TSAA:Lys respectively 45% and 30% below that of the sufficient diets. Performance
      and tissue weights were affected by the Met supply but not by the Met source. In
      TSAA-deficient chickens, ADG and FCR, and protein content in empty body and
      pectoralis major muscles (PM) were lower than in TSAA-sufficient chickens (P <
      0.05). Reducing the Met content of the diet increased the redness value of PM
      (a*) and the hue angle (H degrees ; P < 0.01). The source of Met affected body AA
      composition and the partitioning of body Cys among tissues (P < 0.05). In TSAA
      deficient birds, body Cys mass decreased in the commercial carcass and PM, but
      increased in the rest of the body (P < 0.01). The Met source also had an impact
      on the Cys mass, which was reduced in the commercial carcass and PM of dl-Met
      birds, but higher in the rest, especially in the feathers of TSAA-deficient birds
      (P < 0.05). The Met source, supply, or both altered the AA composition of the
      empty body, mostly in the commercial carcass. In conclusion, a dietary TSAA
      deficiency altered performance, tissue composition and quality traits of PM of
      broilers. There was no impact between dietary dl-Met and dl-HMTBA on performance
      or muscle weight, although the Met source affected the partitioning of Cys among
      tissues. 

PMID- 27030693
TI  - Advanced oxidation process sanitization of eggshell surfaces.
AB  - The microbial quality of eggs entering the hatchery represents an important
      critical control point for biosecurity and pathogen reduction programs in
      integrated poultry production. The development of safe and effective
      interventions to reduce microbial contamination on the surface of eggs will be
      important to improve the overall productivity and microbial food safety of
      poultry and poultry products. The hydrogen peroxide (H2O2) and ultraviolet (UV)
      light advanced oxidation process is a potentially important alternative to
      traditional sanitizers and disinfectants for egg sanitation. The H2O2/UV advanced
      oxidation process was demonstrated previously to be effective in reducing surface
      microbial contamination on eggs. In this study, we evaluated treatment conditions
      affecting the efficacy of H2O2/UV advanced oxidation in order to identify
      operational parameters for the practical application of this technology in egg
      sanitation. The effect of the number of application cycles, UV intensity,
      duration of UV exposure, and egg rotation on the recovery of total aerobic
      bacteria from the surface of eggs was evaluated. Of the conditions evaluated, we
      determined that reduction of total aerobic bacteria from naturally contaminated
      eggs was optimized when eggs were sanitized using 2 repeated application cycles
      with 5 s exposure to 14 mW cm(-2) UV light, and that rotation of the eggs between
      application cycles was unnecessary. Additionally, using these optimized
      conditions, the H2O2/UV process reduced Salmonella by greater than 5 log10 cfu
      egg(-1) on the surface of experimentally contaminated eggs. This study
      demonstrates the potential for practical application of the H2O2/UV advanced
      oxidation process in egg sanitation and its effectiveness in reducing Salmonella
      on eggshell surfaces. 

PMID- 27030694
TI  - Effect of apple pomace fiber and pork fat levels on quality characteristics of
      uncured, reduced-fat chicken sausages.
AB  - The effects of reducing pork fat level from 30 to 25 and 20% by partially
      substituting pork fat with 1 and 2% apple pomace fiber were investigated based on
      the evaluation of physicochemical properties and textural properties of uncured,
      reduced-fat chicken sausages. Increased fat level resulted in decreased moisture
      content, cooking loss, total expressible fluid separation, fat separation, and
      yellowness of uncured, reduced-fat chicken sausages, whereas, an increase in fat
      content, caloric energy, pH, lightness, redness, hardness, cohesiveness,
      gumminess, and chewiness was observed. The results showed that uncured, reduced
      fat chicken sausage samples with increased apple pomace fiber level had lower
      cooking loss, total expressible fluid separation, fat separation, pH, and
      redness. The results from this study show that inclusion of apple pomace fiber in
      the formulation will successfully reduce fat content in emulsion sausages, while
      improving quality characteristics relative to regular-fat (30%) control. 

PMID- 27030695
TI  - Effect of different levels of dietary zinc, manganese, and copper from organic or
      inorganic sources on performance, bacterial chondronecrosis, intramuscular
      collagen characteristics, and occurrence of meat quality defects of broiler
      chickens.
AB  - The aim of the experiment was to assess the effects of 2 dietary levels of trace
      minerals (TM) zinc, manganese, and copper either from organic (OTM) or inorganic
      (ITM) sources on broiler performance, carcass traits, intramuscular collagen
      (IMC) properties, occurrence of hock burns (HB), foot pad dermatitis (FPD),
      femoral and tibia head necrosis, and breast muscle abnormalities (white striping,
      WS; wooden breast, WB; poor cohesion, PC). A total of 3,600 one-day-old male
      chicks were randomly assigned to one of 4 dietary treatments in a 2 * 2 factorial
      arrangement (9 replicates of 100 birds/dietary treatment). Birds were slaughtered
      at 31 (thinning) and 51 d of age. Body weight, daily weight gain (DWG), feed
      intake, feed conversion rate (FCR), and mortality were determined. A significant
      effect of the source of TM supplementation was found only in 51-day-old chickens.
      Birds of the OTM groups were heavier (P < 0.05), with a higher (P < 0.05) DWG and
      a better FCR (P < 0.05) compared with those of the ITM groups. OTM significantly
      reduced the lesion scores of femoral head (P = 0.004) and total leg (femur +
      tibia, P = 0.02) compared to ITM, which is mainly caused by the reduction of the
      percentages of femoral head transitional degeneration (FHT, P = 0.04) and femoral
      head necrosis (FHN, P = 0.07). Carcass traits were similar among the experimental
      groups. No alleviating effect of TM administration on the incidence of FPD and HB
      in 31- and 51-day-old chickens was found. Similarly, the occurrence and the
      degrees of WS and WB in 51-day-old chickens was affected neither by the doses nor
      by the source of TM supplied. IMC characteristics of broiler pectoral muscle were
      not affected (P > 0.05) by the different sources and doses of TM administrated. 

PMID- 27030696
TI  - Identification of the Paneth cells in chicken small intestine.
AB  - The Paneth cells are highly specialized cells in the epithelium of the small
      intestine of many vertebrate species. These cells reside at the base of crypts of
      the Lieberkuhn and contain abundant secretory granules. Previous studies
      suggesting the existence of Paneth cells in the chicken (Gallus gallus) remained
      controversial. Here we seek to identify the Paneth cells in the chicken small
      intestine through morphological examination and specific gene expression.
      Histological staining and transmission electron microscope confirmed the presence
      of granulated secretory cells at the base of the crypts in the chicken small
      intestine. Western blotting experiment also manifested the expression of lysozyme
      protein, which is specifically secreted by the Paneth cells in the small
      intestine. Moreover, lysozyme c and lysozyme g mRNAs were expressed in the small
      intestine of chickens at different ages. Lysozyme c mRNA, in particular, was
      located at the base of the small intestinal crypts as displayed by in situ
      hybridization. Collectively, we provide evidences that the Paneth cells indeed
      exist in the small intestine of the chicken. 

PMID- 27030697
TI  - 'He said, she said': assessing dyadic agreement of reported sexual behaviour and
      decision-making among an HIV sero-discordant couples cohort in Uganda.
AB  - BACKGROUND: The intimate nature of sexuality makes it challenging to accurately
      measure sexual behaviour. To assess response reliability, we examined agreement
      between couples in heterosexual HIV sero-discordant partnership on survey
      questions regarding condom use and sexual decision-making. METHODS: Data for this
      analysis come from baseline data from a cohort study of HIV sero-discordant
      couples in Jinja, Uganda. We examined the degree of agreement between male and
      female partners on standard measures of sexual behaviour using the kappa (kappa)
      statistic and 95% confidence intervals (95% CIs). RESULTS: Among 409 couples, the
      median age for the male partner was 41 [interquartile range (IQR) 35-48] years
      and the female partner was 35 (IQR 30-40) years. Among 58.2% of the couples, the
      male was the HIV-positive partner. Questions with high or substantial couple
      agreement included condom use at last sex (kappa=0.635, 95% CI 0.551-0.718) and
      frequency of condom use (kappa=0.625, 95% CI 0.551-0.698). Questions with low or
      fair couple agreement included decision-making regarding condom use (kappa=0.385,
      95% CI 0.319-0.451), wanting more biological children (kappa=0.375, 95% CI 0.301
      0.449) and deciding when to have sex (kappa=0.236, 95% CI 0.167-0.306).
      CONCLUSIONS: Survey questions assessing condom use had the highest level of
      couple agreement and questions regarding sexual decision-making and fertility
      desire had low couple agreement. Questions with high agreement have increased
      reliability and reduced measurement bias; however, questions with low agreement
      between couples identify important areas for further investigation, particularly
      perceived relationship control and gender differences.

PMID- 27030698
TI  - The effect of depot medroxyprogesterone acetate on postnatal depression: a
      randomised controlled trial.
AB  - BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is the most commonly used
      hormonal contraceptive method in South Africa. It is frequently administered in
      the immediate postnatal period, yet it is unclear whether it affects the risk of
      postnatal depression (PND). AIM: To determine whether DMPA increases the risk of
      PND compared with the copper-containing intrauterine device (IUD) when
      administered after delivery. DESIGN AND SETTING: A single-blind randomised
      controlled trial conducted at two teaching hospitals in East London, South
      Africa. METHODS: Eligible, consenting women (N=242) requiring postnatal
      contraception were randomised to receive DMPA or an IUD within 48 hours of
      childbirth and interviewed at 1 and 3 months postpartum. Depression was measured
      using the Beck Depression Inventory (BDI-II) and the Edinburgh Postnatal
      Depression Scale (EPDS). Resumption of sexual intercourse, menstrual symptoms and
      breastfeeding rates were also assessed. RESULTS: One-month EPDS depression scores
      were statistically significantly higher in the DMPA arm compared with IUD arm
      (p=0.04). Three-month BDI-II scores were significantly higher in the DMPA arm
      than in the IUD arm (p=0.002) and, according to the BDI-II but not the EPDS, more
      women in the DMPA arm had major depression at this time-point (8 vs 2; p=0.05).
      There were no statistically significant differences in other outcome measures
      except that fewer women had resumed sexual activity by 1 month postpartum in the
      DMPA arm (13% vs 26%; p=0.02). CONCLUSIONS: The possibility that immediate
      postnatal DMPA use is associated with depression cannot be excluded. These
      findings justify further research with longer follow-up. CLINICAL TRIAL NUMBER:
      PACTR201209000419241.

PMID- 27030699
TI  - Systematic Review of Defibrillation Threshold Testing at De Novo Implantation.
AB  - BACKGROUND: Recent results from the largest multicenter randomized trial
      (Shockless IMPLant Evaluation [SIMPLE]) on defibrillation threshold (DFT) testing
      suggest that while shock testing seems safe, it does not reduce the risk of
      failed shocks or prolong survival. A contemporary systematic review of DFT versus
      no-DFT testing at the time of implantable cardioverter-defibrillator implantation
      was performed to evaluate the current evidence and to assess the impact of the
      SIMPLE study. METHODS AND RESULTS: Electronic searches were performed using 6
      databases from their inception to March 2014. Relevant studies investigating
      implant DFT were identified. Data were extracted and analyzed according to
      predefined clinical end points. Predefined outcomes for interrogation were all
      cause mortality, composite end point of implantable cardioverter-defibrillator
      efficacy (arrhythmic deaths and ineffective shocks), and composite safety end
      point (the sum of complications recorded at 30 days). Meta-analysis was performed
      including 13 studies and 9740 patients. No significant differences between DFT
      versus no-DFT cohorts were found in terms of all-cause mortality (risk ratio,
      0.90; 95% confidence interval, 0.71-1.15; P=0.41), composite efficacy outcome
      (risk ratio, 1.24; 95% confidence interval, 0.65-3.37; P=0.51), and 30-day
      postimplant complications (risk ratio, 1.18; 95% confidence interval, 0.87-1.60;
      P=0.29). No significant difference was found in the trends observed when the
      results of the SIMPLE study were excluded or included. CONCLUSIONS: This
      systematic review of contemporary data suggests a modest average effect of DFT,
      if any, in terms of mortality, shock efficacy, or safety. Therefore, DFT testing
      should no longer be compulsory during de novo implantation. However, DFT testing
      may still be clinically relevant in specific patient populations.

PMID- 27030700
TI  - Arrhythmogenicity of Anti-Ro/SSA Antibodies in Patients With Torsades de Pointes.
AB  - BACKGROUND: In patients with autoimmune disease, anti-Ro/SSA antibodies (anti
      Ro/SSA) are responsible for a novel autoimmune-associated long-QT syndrome by
      targeting the hERG potassium channel and inhibiting the related current (IKr).
      Because anti-Ro/SSA are also present in a significant proportion of healthy
      subjects and may be associated with torsades de pointes (TdP) arrhythmia, we
      tested the hypothesis that anti-Ro/SSA may represent a silent risk factor in
      patients developing TdP. METHODS AND RESULTS: Twenty-five consecutive patients
      who experienced TdP were prospectively collected independent of ongoing therapies
      and concomitant diseases. Anti-Ro/SSA were detected by fluoroenzyme immunoassay,
      immuno-Western blotting, and line-blot immunoassay. Purified IgGs from anti
      Ro/SSA-positive and anti-Ro/SSA-negative patients were tested on IKr using HEK293
      cells stably expressing the hERG channel. As expected, in TdP patients, many
      known corrected QT interval-prolonging risk factors were simultaneously present,
      including hypokalemia that was the most common (52%). Anti-Ro/SSA were present in
      60% of the subjects, mostly the anti-Ro/SSA-52-kD subtype detected by immuno
      Western blotting only. A history of autoimmune disease was found in only 2 of
      anti-Ro/SSA-positive patients. Experimental data demonstrated that purified anti
      Ro/SSA-positive IgGs significantly inhibited IKr and cross reacted with hERG
      channel proteins. Moreover, anti-Ro/SSA-positive sera exhibited high reactivity
      with a peptide corresponding to the hERG-channel pore-forming region.
      CONCLUSIONS: Anti-Ro/SSA may represent a clinically silent novel risk factor for
      TdP development via an autoimmune-mediated electrophysiological interference with
      the hERG channel. We propose that TdP patients may benefit from specific anti
      Ro/SSA testing even in the absence of autoimmune diseases as immunomodulating
      therapies may be effective in shortening corrected QT interval and reducing TdP
      recurrence risk.

PMID- 27030701
TI  - Role of Bilateral Sympathectomy in the Treatment of Refractory Ventricular
      Arrhythmias in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

PMID- 27030702
TI  - Executive Summary of the Key Concepts.

PMID- 27030703
TI  - The Nurse as Provider, Planner, and Provocateur.

PMID- 27030704
TI  - Nursing's Impact on Healthcare Facility Design.

PMID- 27030705
TI  - Commentary by Cahnman.

PMID- 27030706
TI  - Commentary by Warren Kerr AM.

PMID- 27030707
TI  - Organizing for Project Success: A Report From the Academy for Healthcare
      Infrastructure.

PMID- 27030710
TI  - Spinal nociceptive transmission by mechanical stimulation of bone marrow.
AB  - BACKGROUND: Since bone marrow receives innervation from A-delta and C-fibers and
      since an increase in intramedullary pressure in bone marrow may induce acute pain
      in orthopedic patients during surgery and chronic pain in patients with bone
      marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous
      lesions, such as osteomyelitis and bone cancer, are also known to produce
      cutaneous hypersensitivity, which might be referred pain from bone. However,
      little is known about pain perception in bone marrow and referred pain induced by
      bone disease. Thus, we carried out an in vivo electrophysiological study and
      behavioral study to determine whether increased intraosseous pressure of the
      femur induces acute pain and whether increased intraosseous pressure induces
      referred pain in the corresponding receptive fields of the skin. RESULTS:
      Intraosseous balloon inflation caused spontaneous pain-related behavior and
      mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal
      activities of spinal dorsal horn neurons were extracellularly isolated, and then
      evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous
      balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which
      had somatic receptive fields at the lower back and thigh, were obtained. Sixty
      two percent of the wide-dynamic-range neurons (24/39) and 86% of the high
      threshold neurons (12/14) responded to intraosseous balloon inflation, while none
      of the low-threshold neurons (0/41) responded to intraosseous balloon inflation.
      Spinally administered morphine (1 ug) abolished balloon inflation-induced
      spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and
      also suppressed evoked activities of wide-dynamic-range neurons to noxious
      cutaneous stimulation and intraosseous balloon inflation. CONCLUSIONS: The
      results suggest that mechanical stimulation to bone marrow produces nociception,
      concomitantly producing its referred pain in the corresponding skin fields. These
      mechanisms might contribute to pain caused by skeletal diseases.

PMID- 27030709
TI  - Functional and structural characterization of axonal opioid receptors as targets
      for analgesia.
AB  - BACKGROUND: Opioids are the gold standard for the treatment of acute pain despite
      serious side effects in the central and enteric nervous system. u-opioid
      receptors (MOPs) are expressed and functional at the terminals of sensory axons,
      when activated by exogenous or endogenous ligands. However, the presence and
      function of MOP along nociceptive axons remains controversial particularly in
      naive animals. Here, we characterized axonal MOPs by immunofluorescence,
      ultrastructural, and functional analyses. Furthermore, we evaluated hypertonic
      saline as a possible enhancer of opioid receptor function. RESULTS: Comparative
      immunolabeling showed that, among several tested antibodies, which all provided
      specific MOP detection in the rat central nervous system (CNS), only one
      monoclonal MOP-antibody yielded specificity and reproducibility for MOP detection
      in the rat peripheral nervous system including the sciatic nerve. Double
      immunolabeling documented that MOP immunoreactivity was confined to calcitonin
      gene-related peptide (CGRP) positive fibers and fiber bundles. Almost identical
      labeling and double labeling patterns were found using mcherry-immunolabeling on
      sciatic nerves of mice producing a MOP-mcherry fusion protein (MOP-mcherry knock
      in mice). Preembedding immunogold electron microscopy on MOP-mcherry knock-in
      sciatic nerves indicated presence of MOP in cytoplasm and at membranes of
      unmyelinated axons. Application of [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin
      (DAMGO) or fentanyl dose-dependently inhibited depolarization-induced CGRP
      release from rat sciatic nerve axons ex vivo, which was blocked by naloxone. When
      the lipophilic opioid fentanyl was applied perisciatically in naive Wistar rats,
      mechanical nociceptive thresholds increased. Subthreshold doses of fentanyl or
      the hydrophilic opioid DAMGO were only effective if injected together with
      hypertonic saline. In vitro, using beta-arrestin-2/MOP double-transfected human
      embryonic kidney cells, DAMGO as well as fentanyl lead to a recruitment of beta
      arrestin-2 to the membrane followed by a beta-arrestin-2 reappearance in the
      cytosol and MOP internalization. Pretreatment with hypertonic saline prevented
      MOP internalization. CONCLUSION: MOPs are present and functional in the axonal
      membrane from naive animals. Hypertonic saline acutely decreases ligand-induced
      internalization of MOP and thereby might improve MOP function. Further studies
      should explore potential clinical applications of opioids together with enhancers
      for regional analgesia.

PMID- 27030711
TI  - Differences in electrophysiological properties of functionally identified
      nociceptive sensory neurons in an animal model of cancer-induced bone pain.
AB  - BACKGROUND: Bone cancer pain is often severe, yet little is known about
      mechanisms generating this type of chronic pain. While previous studies have
      identified functional alterations in peripheral sensory neurons that correlate
      with bone tumours, none has provided direct evidence correlating behavioural
      nociceptive responses with properties of sensory neurons in an intact bone cancer
      model. RESULTS: In a rat model of prostate cancer-induced bone pain, we confirmed
      tactile hypersensitivity using the von Frey test. Subsequently, we recorded
      intracellularly from dorsal root ganglion neurons in vivo in anesthetized
      animals. Neurons remained connected to their peripheral receptive terminals and
      were classified on the basis of action potential properties, responses to dorsal
      root stimulation, and to mechanical stimulation of the respective peripheral
      receptive fields. Neurons included C-, Adelta-, and Abeta-fibre nociceptors,
      identified by their expression of substance P. We suggest that bone tumour may
      induce phenotypic changes in peripheral nociceptors and that these could
      contribute to bone cancer pain. CONCLUSIONS: This work represents a significant
      technical and conceptual advance in the study of peripheral nociceptor functions
      in the development of cancer-induced bone pain. This is the first study to report
      that changes in sensitivity and excitability of dorsal root ganglion primary
      afferents directly correspond to mechanical allodynia and hyperalgesia behaviours
      following prostate cancer cell injection into the femur of rats. Furthermore, our
      unique combination of techniques has allowed us to follow, in a single neuron,
      mechanical pain-related behaviours, electrophysiological changes in action
      potential properties, and dorsal root substance P expression. These data provide
      a more complete understanding of this unique pain state at the cellular level
      that may allow for future development of mechanism-based treatments for cancer
      induced bone pain.

PMID- 27030712
TI  - Improvements in impaired GABA and GAD65/67 production in the spinal dorsal horn
      contribute to exercise-induced hypoalgesia in a mouse model of neuropathic pain.
AB  - BACKGROUND: Physical exercise effectively attenuates neuropathic pain, and
      multiple events including the inhibition of activated glial cells in the spinal
      dorsal horn, activation of the descending pain inhibitory system, and reductions
      in pro-inflammatory cytokines in injured peripheral nerves may contribute to
      exercise-induced hypoalgesia. Since fewer GABAergic hypoalgesic interneurons
      exist in the dorsal horn in neuropathic pain model animals, the recovery of
      impaired GABAergic inhibition in the dorsal horn may improve pain behavior. We
      herein determined whether the production of gamma-aminobutyric acid (GABA) and
      glutamic acid decarboxylase (GAD) in the dorsal horn is restored by treadmill
      running and contributes to exercise-induced hypoalgesia in neuropathic pain model
      mice. C57BL/6 J mice underwent partial sciatic nerve ligation (PSL). PSL-Runner
      mice ran on a treadmill at 7 m/min for 60 min/day, 5 days/week, from two days
      after PSL. RESULTS: Mechanical allodynia and heat hyperalgesia developed in PSL
      Sedentary mice but were significantly attenuated in PSL-Runner mice. PSL markedly
      decreased GABA and GAD65/67 levels in neuropils in the ipsilateral dorsal horn,
      while treadmill running inhibited these reductions. GABA+ neuronal nuclei+
      interneuron numbers in the ipsilateral dorsal horn were significantly decreased
      in PSL-Sedentary mice but not in PSL-Runner mice. Pain behavior thresholds
      positively correlated with GABA and GAD65/67 levels and GABAergic interneuron
      numbers in the ipsilateral dorsal horns of PSL-Sedentary and -Runner mice.
      CONCLUSIONS: Treadmill running prevented PSL-induced reductions in GAD65/67
      production, and, thus, GABA levels may be retained in interneurons and neuropils
      in the superficial dorsal horn. Therefore, improvements in impaired GABAergic
      inhibition may be involved in exercise-induced hypoalgesia.

PMID- 27030713
TI  - Functional characterization of a mouse model for central post-stroke pain.
AB  - BACKGROUND: Stroke patients often suffer from a central neuropathic pain syndrome
      called central post-stroke pain. This syndrome is characterized by evoked pain
      hypersensitivity as well as spontaneous, on-going pain in the body area affected
      by the stroke. Clinical evidence strongly suggests a dysfunction in central pain
      pathways as an important pathophysiological factor in the development of central
      post-stroke pain, but the exact underlying mechanisms remain poorly understood.
      To elucidate the underlying pathophysiology of central post-stroke pain, we
      generated a mouse model that is based on a unilateral stereotactic lesion of the
      thalamic ventral posterolateral nucleus, which typically causes central post
      stroke pain in humans. RESULTS: Behavioral analysis showed that the sensory
      changes in our model are comparable to the sensory abnormalities observed in
      patients suffering from central post-stroke pain. Surprisingly, pharmacological
      inhibition of spinal and peripheral key components of the pain system had no
      effect on the induction or maintenance of the evoked hypersensitivity observed in
      our model. In contrast, microinjection of lidocaine into the thalamic lesion
      completely reversed injury-induced hypersensitivity. CONCLUSIONS: These results
      suggest that the evoked hypersensitivity observed in central post-stroke pain is
      causally linked to on-going neuronal activity in the lateral thalamus.

PMID- 27030714
TI  - A quantitative study of neurochemically defined excitatory interneuron
      populations in laminae I-III of the mouse spinal cord.
AB  - BACKGROUND: Excitatory interneurons account for the majority of neurons in
      laminae I-III, but their functions are poorly understood. Several neurochemical
      markers are largely restricted to excitatory interneuron populations, but we have
      limited knowledge about the size of these populations or their overlap. The
      present study was designed to investigate this issue by quantifying the neuronal
      populations that express somatostatin (SST), neurokinin B (NKB), neurotensin,
      gastrin-releasing peptide (GRP) and the gamma isoform of protein kinase C
      (PKCgamma), and assessing the extent to which they overlapped. Since it has been
      reported that calretinin- and SST-expressing cells have different functions, we
      also looked for co-localisation of calretinin and SST. RESULTS: SST,
      preprotachykinin B (PPTB, the precursor of NKB), neurotensin, PKCgamma or
      calretinin were detected with antibodies, while cells expressing GRP were
      identified in a mouse line (GRP-EGFP) in which enhanced green fluorescent protein
      (EGFP) was expressed under control of the GRP promoter. We found that SST-,
      neurotensin-, PPTB- and PKCgamma-expressing cells accounted for 44%, 7%, 12% and
      21% of the neurons in laminae I-II, and 16%, 8%, 4% and 14% of those in lamina
      III, respectively. GRP-EGFP cells made up 11% of the neuronal population in
      laminae I-II. The neurotensin, PPTB and GRP-EGFP populations showed very limited
      overlap, and we estimate that between them they account for ~40% of the
      excitatory interneurons in laminae I-II. SST which is expressed by ~60% of
      excitatory interneurons in this region, was found in each of these populations,
      as well as in cells that did not express any of the other peptides. Neurotensin
      and PPTB were often found in cells with PKCgamma, and between them, constituted
      around 60% of the PKCgamma cells. Surprisingly, we found extensive co
      localisation of SST and calretinin. CONCLUSIONS: These results suggest that cells
      expressing neurotensin, NKB or GRP form largely non-overlapping sets that are
      likely to correspond to functional populations. In contrast, SST is widely
      expressed by excitatory interneurons that are likely to be functionally
      heterogeneous.

PMID- 27030715
TI  - Regulation of transient receptor potential vanilloid 1 expression in trigeminal
      ganglion neurons via methyl-CpG binding protein 2 signaling contributes tongue
      heat sensitivity and inflammatory hyperalgesia in mice.
AB  - BACKGROUND: Pain hypoalgesia has been reported in Rett syndrome patients, a
      severe neurodevelopmental disorder which can be attributed to mutations in the
      methyl-CpG binding protein 2 (MeCP2). Here, we examined the role of MeCP2
      signaling in tongue heat sensitivity in the normal and inflamed state using Mecp2
      heterozygous (Mecp2(+/-)) mice. RESULTS: Heat hypoalgesia of the tongue occurred
      in Mecp2(+/-) mice and submucosal injection of complete Freund's adjuvant into
      the tongue produced a long-lasting heat hyperalgesia at the inflamed site in wild
      type mice but not in Mecp2(+/-) mice. Transient receptor potential vanilloid 1
      was expressed in a large number of MeCP2-immunoreactive trigeminal ganglion
      neurons innervating the tongue in both wild-type and Mecp2(+/-) mice (70.9% in
      wild type; 72.1% in Mecp2(+/-)). The number of transient receptor potential
      vanilloid 1-immunoreactive trigeminal ganglion neurons innervating the tongue was
      smaller in Mecp2(+/-) mice relative to wild-type mice (30.5% in wild type; 20.2%
      in Mecp2(+/-)). Following complete Freund's adjuvant injection, the number of
      transient receptor potential vanilloid 1- and MeCP2-immunoreactive trigeminal
      ganglion neurons innervating the tongue, as well as MeCP2 protein expression in
      trigeminal ganglion, was significantly increased in wild-type mice but not in
      Mecp2(+/-) mice. Additionally, tongue heat hyperalgesia following complete
      Freund's adjuvant injection was completely suppressed by the administration of
      SB366791, a transient receptor potential vanilloid 1 antagonist, in the tongue.
      CONCLUSIONS: These findings indicate that tongue heat sensitivity and
      hypersensitivity are dependent on the expression of transient receptor potential
      vanilloid 1 which is regulated via MeCP2 signaling in trigeminal ganglion neurons
      innervating the tongue.

PMID- 27030716
TI  - Connexin 43 contributes to ectopic orofacial pain following inferior alveolar
      nerve injury.
AB  - BACKGROUND: Clinically, it is well known that injury of mandibular nerve fiber
      induces persistent ectopic pain which can spread to a wide area of the orofacial
      region innervated by the uninjured trigeminal nerve branches. However, the exact
      mechanism of such persistent ectopic orofacial pain is not still known. The
      present study was undertaken to determine the role of connexin 43 in the
      trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin
      induced by inferior alveolar nerve injury. Here, we examined changes in orofacial
      mechanical sensitivity following inferior alveolar nerve injury. Furthermore,
      changes in connexin 43 expression in the trigeminal ganglion and its localization
      in the trigeminal ganglion were also examined. In addition, we investigated the
      functional significance of connexin 43 in relation to mechanical allodynia by
      using a selective gap junction blocker (Gap27). RESULTS: Long-lasting mechanical
      allodynia in the whisker pad skin and the upper eyelid skin, and activation of
      satellite glial cells in the trigeminal ganglion, were induced after inferior
      alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial
      cells encircling trigeminal ganglion neurons innervating the whisker pad skin,
      and the connexin 43 protein expression was significantly increased after inferior
      alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion
      significantly reduced satellite glial cell activation and mechanical
      hypersensitivity in the whisker pad skin. Moreover, the marked activation of
      satellite glial cells encircling trigeminal ganglion neurons innervating the
      whisker pad skin following inferior alveolar nerve injury implies that the
      satellite glial cell activation exerts a major influence on the excitability of
      nociceptive trigeminal ganglion neurons. CONCLUSIONS: These findings indicate
      that the propagation of satellite glial cell activation throughout the trigeminal
      ganglion via gap junctions, which are composed of connexin 43, plays a pivotal
      role in ectopic mechanical hypersensitivity in whisker pad skin following
      inferior alveolar nerve injury.

PMID- 27030717
TI  - Crosstalk between astrocytic CXCL12 and microglial CXCR4 contributes to the
      development of neuropathic pain.
AB  - BACKGROUND: Chemokine axis chemokine C-X-C motif ligand 12/C-X-C chemokine
      receptor type 4 (CXCL12/CXCR4) is an emerging pain modulator, but mechanisms for
      its involvement in neuropathic pain remain unclear. Here, we aimed to study
      whether CXCL12/CXCR4 axis modulated the development of neuropathic pain via glial
      mechanisms. In this study, two mouse models of neuropathic pain, namely partial
      sciatic nerve ligation (pSNL) model and chronic post-ischemia pain (CPIP) model,
      were used. RESULTS: In the dorsal horn of L3-L5 segment of spinal cord, CXCL12
      and CXCR4 were expressed in both astrocyte and microglia in normal mice. In the
      pSNL or CPIP model, the expression level of CXCL12 in the ipsilateral L3-L5
      segment of mice spinal cord was increased in an astrocyte-dependent manner on
      post-operative day (POD) 3. Intrathecal administration of CXCL12 with AMD3100
      (CXCR4 antagonist) or minocycline (microglia activation inhibitor), but not
      fluorocitrate (astrocyte activation inhibitor), reversed CXCL12-indued mechanical
      allodynia in naive mice. In these models, AMD3100 and AMD3465 (CXCR4 antagonist),
      administered daily from 1 h before surgery and up to POD 3, attenuated the
      development of mechanical allodynia. Moreover, AMD3100 administered daily from 1
      h before surgery and up to POD 3 downregulated mRNA levels of tumor necrosis
      factor alpha, interleukin 1beta, and interleukin 6 in the ipsilateral L3-L5
      segment of spinal cord in the pSNL and CPIP models on POD 3. CONCLUSION: This
      study demonstrates the crosstalk between astrocytic CXCL12 and microglial CXCR4
      in the pathogenesis of neuropathic pain using pSNL and CPIP models. Our results
      offer insights for the future research on CXCL12/CXCR4 axis and neuropathic pain
      therapy.

PMID- 27030718
TI  - Epidural optogenetics for controlled analgesia.
AB  - BACKGROUND: Optogenetic tools enable cell selective and temporally precise
      control of neuronal activity; yet, difficulties in delivering sufficient light to
      the spinal cord of freely behaving animals have hampered the use of spinal
      optogenetic approaches to produce analgesia. We describe an epidural optic fiber
      designed for chronic spinal optogenetics that enables the precise delivery of
      light at multiple wavelengths to the spinal cord dorsal horn and sensory
      afferents. RESULTS: The epidural delivery of light enabled the optogenetic
      modulation of nociceptive processes at the spinal level. The acute and repeated
      activation of channelrhodopsin-2 expressing nociceptive afferents produced robust
      nocifensive behavior and mechanical sensitization in freely behaving mice,
      respectively. The optogenetic inhibition of GABAergic interneurons in the spinal
      cord dorsal horn through the activation of archaerhodopsin also produced a
      transient, but selective induction of mechanical hypersensitivity. Finally, we
      demonstrate the capacity of optogenetics to produce analgesia in freely behaving
      mice through the inhibition of nociceptive afferents via archaerhodopsin.
      CONCLUSION: Epidural optogenetics provides a robust and powerful solution for
      activation of both excitatory and inhibitory opsins in sensory processing
      pathways. Our results demonstrate the potential of spinal optogenetics to
      modulate sensory behavior and produce analgesia in freely behaving animals.

PMID- 27030719
TI  - Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid
      autacoids: Implications for idiopathic pain syndromes?
AB  - BACKGROUND: Chronic idiopathic pain syndromes are major causes of personal
      suffering, disability, and societal expense. Dietary n-6 linoleic acid has
      increased markedly in modern industrialized populations over the past century.
      These high amounts of linoleic acid could hypothetically predispose to physical
      pain by increasing the production of pro-nociceptive linoleic acid-derived lipid
      autacoids and by interfering with the production of anti-nociceptive lipid
      autacoids derived from n-3 fatty acids. Here, we used a rat model to determine
      the effect of increasing dietary linoleic acid as a controlled variable for 15
      weeks on nociceptive lipid autacoids and their precursor n-6 and n-3 fatty acids
      in tissues associated with idiopathic pain syndromes. RESULTS: Increasing dietary
      linoleic acid markedly increased the abundance of linoleic acid and its pro
      nociceptive derivatives and reduced the abundance of n-3 eicosapentaenoic acid
      and docosahexaenoic acid and their anti-nociceptive monoepoxide derivatives. Diet
      induced changes occurred in a tissue-specific manner, with marked alterations of
      nociceptive lipid autacoids in both peripheral and central tissues, and the most
      pronounced changes in their fatty acid precursors in peripheral tissues.
      CONCLUSIONS: The present findings provide biochemical support for the hypothesis
      that the high linoleic acid content of modern industrialized diets may create a
      biochemical susceptibility to develop chronic pain. Dietary linoleic acid
      lowering should be further investigated as part of an integrative strategy for
      the prevention and management of idiopathic pain syndromes.

PMID- 27030720
TI  - Involvement of NIPSNAP1, a neuropeptide nocistatin-interacting protein, in
      inflammatory pain.
AB  - BACKGROUND: Chronic pain associated with inflammation is an important clinical
      problem, and the underlying mechanisms remain poorly understood. 4
      Nitrophenylphosphatase domain and nonneuronal SNAP25-like protein homolog
      (NIPSNAP) 1, an interacting protein with neuropeptide nocistatin, is implicated
      in the inhibition of tactile pain allodynia. Although nocistatin inhibits some
      inflammatory pain responses, whether NIPSNAP1 affects inflammatory pain appears
      to be unclear. Here, we examined the nociceptive behavioral response of NIPSNAP1
      deficient mice and the expression of NIPSNAP1 following peripheral inflammation
      to determine the contribution of NIPSNAP1 to inflammatory pain. RESULTS:
      Nociceptive behavioral response increased in phase II of the formalin test,
      particularly during the later stage (26-50 min) in NIPSNAP1-deficient mice,
      although the response during phase I (0-15 min) was not significantly different
      between the deficient and wild-type mice. Moreover, phosphorylation of
      extracellular signal-related kinase was enhanced in the spinal dorsal horn of the
      deficient mice. The prolonged inflammatory pain induced by carrageenan and
      complete Freund's adjuvant was exacerbated in NIPSNAP1-deficient mice. NIPSNAP1
      mRNA was expressed in small- and medium-sized neurons of the dorsal root ganglion
      and motor neurons of the spinal cord. In the formalin test, NIPSNAP1 mRNA was
      slightly increased in dorsal root ganglion but not in the spinal cord. In
      contrast, NIPSNAP1 mRNA levels in dorsal root ganglion were significantly
      decreased during 24-48 h after carrageenan injection. Prostaglandin E2, a major
      mediator of inflammation, stimulated NIPSNAP1 mRNA expression via the cAMP
      protein kinase A signaling pathway in isolated dorsal root ganglion cells.
      CONCLUSIONS: These results suggest that changes in NIPSNAP1 expression may
      contribute to the pathogenesis of inflammatory pain.

PMID- 27030721
TI  - Dorsal root ganglion transcriptome analysis following peripheral nerve injury in
      mice.
AB  - BACKGROUND: Peripheral nerve injury leads to changes in gene expression in
      primary sensory neurons of the injured dorsal root ganglia. These changes are
      believed to be involved in neuropathic pain genesis. Previously, these changes
      have been identified using gene microarrays or next generation RNA sequencing
      with poly-A tail selection, but these approaches cannot provide a more thorough
      analysis of gene expression alterations after nerve injury. METHODS: The present
      study chose to eliminate mRNA poly-A tail selection and perform strand-specific
      next generation RNA sequencing to analyze whole transcriptomes in the injured
      dorsal root ganglia following spinal nerve ligation. Quantitative real-time
      reverse transcriptase polymerase chain reaction assay was carried out to verify
      the changes of some differentially expressed RNAs in the injured dorsal root
      ganglia after spinal nerve ligation. RESULTS: Our results showed that more than
      50 million (M) paired mapped sequences with strand information were yielded in
      each group (51.87 M-56.12 M in sham vs. 51.08 M-57.99 M in spinal nerve
      ligation). Six days after spinal nerve ligation, expression levels of 11,163 out
      of a total of 27,463 identified genes in the injured dorsal root ganglia
      significantly changed, of which 52.14% were upregulated and 47.86% downregulated.
      The largest transcriptional changes were observed in protein-coding genes (91.5%)
      followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs,
      the most significant changes were seen in long interspersed noncoding RNAs
      followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a
      notable proportion of reads aligning to intronic regions in both groups (44.0% in
      sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase
      chain reaction, we confirmed consistent differential expression of selected genes
      including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following
      spinal nerve ligation. CONCLUSION: Our findings suggest that next generation RNA
      sequencing can be used as a promising approach to analyze the changes of whole
      transcriptomes in dorsal root ganglia following nerve injury and to possibly
      identify new targets for prevention and treatment of neuropathic pain.

PMID- 27030722
TI  - Characterization of cutaneous and articular sensory neurons.
AB  - BACKGROUND: A wide range of stimuli can activate sensory neurons and neurons
      innervating specific tissues often have distinct properties. Here, we used
      retrograde tracing to identify sensory neurons innervating the hind paw skin
      (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry
      and electrophysiology analysis to determine the neurochemical phenotype of
      cutaneous and articular neurons, as well as their electrical and chemical
      excitability. RESULTS: Immunohistochemistry analysis using RetroBeads as a
      retrograde tracer confirmed previous data that cutaneous and articular neurons
      are a mixture of myelinated and unmyelinated neurons, and the majority of both
      populations are peptidergic. In whole-cell patch-clamp recordings from cultured
      dorsal root ganglion neurons, voltage-gated inward currents and action potential
      parameters were largely similar between articular and cutaneous neurons, although
      cutaneous neuron action potentials had a longer half-peak duration (HPD). An
      assessment of chemical sensitivity showed that all neurons responded to a pH 5.0
      solution, but that acid-sensing ion channel (ASIC) currents, determined by
      inhibition with the nonselective acid-sensing ion channel antagonist benzamil,
      were of a greater magnitude in cutaneous compared to articular neurons. Forty to
      fifty percent of cutaneous and articular neurons responded to capsaicin,
      cinnamaldehyde, and menthol, indicating similar expression levels of transient
      receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1
      (TRPA1), and transient receptor potential melastatin 8 (TRPM8), respectively. By
      contrast, significantly more articular neurons responded to ATP than cutaneous
      neurons. CONCLUSION: This work makes a detailed characterization of cutaneous and
      articular sensory neurons and highlights the importance of making recordings from
      identified neuronal populations: sensory neurons innervating different tissues
      have subtly different properties, possibly reflecting different functions.

PMID- 27030725
TI  - Cloning and characterization of two thermo- and salt-tolerant oligoalginate
      lyases from marine bacterium Halomonas sp.
AB  - Two new alginate lyase genes, oalY1 and oalY2, have been cloned from the newly
      isolated marine bacterium Halomonas sp. QY114 and expressed in Escherichia coli
      The deduced alginate lyases, OalY1 and OalY2, belonged to polysaccharide lyase
      (PL) family 17 and showed less than 45% amino acid identity with all of the
      characterized oligoalginate lyases. OalY1 and OalY2 exhibited the highest
      activities at 45 degrees C and 50 degrees C, respectively. Both of them showed
      more than 50% of the highest activity at 60 degrees C, and 20% at 80 degrees C.
      In addition, they were salt-dependent and salt-tolerant since both of them showed
      the highest activity in the presence of 0.5 M NaCl and preserved 63% and 68% of
      activity in the presence of 3 M NaCl. Significantly, OalY1 and OalY2 could
      degrade both polyM and polyG blocks into alginate monosaccharides in an exo-lytic
      type, indicating that they are bifunctional alginate lyases. In conclusion, our
      study indicated that OalY1 and OalY2 are good candidates for alginate
      saccharification application, and the salt-tolerance may present an exciting new
      concept for biofuel production from native brown seaweeds.

PMID- 27030723
TI  - Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human
      P2X3 receptors and inflammatory pain.
AB  - BACKGROUND: A growing body of evidence suggests that ATP-gated P2X3 receptors
      (P2X3Rs) are implicated in chronic pain. We address the possibility that stable,
      synthetic analogs of diadenosine tetraphosphate (Ap4A) might induce
      antinociceptive effects by inhibiting P2X3Rs in peripheral sensory neurons.
      RESULTS: The effects of two stable, synthetic Ap4A analogs (AppNHppA and
      AppCH2ppA) are studied firstly in vitro on HEK293 cells expressing recombinant
      rat P2XRs (P2X2Rs, P2X3Rs, P2X4Rs, and P2X7Rs) and then using native rat brain
      cells (cultured trigeminal, nodose, or dorsal root ganglion neurons). Thereafter,
      the action of these stable, synthetic Ap4A analogs on inflammatory pain and
      thermal hyperalgesia is studied through the measurement of antinociceptive
      effects in formalin and Hargreaves plantar tests in rats in vivo. In vitro
      inhibition of rat P2X3Rs (not P2X2Rs, P2X4Rs nor P2X7Rs) is shown to take place
      mediated by high-affinity desensitization (at low concentrations; IC50 values 100
      250 nM) giving way to only weak partial agonism at much higher concentrations
      (EC50 values >= 10 uM). Similar inhibitory activity is observed with human
      recombinant P2X3Rs. The inhibitory effects of AppNHppA on nodose, dorsal root,
      and trigeminal neuron whole cell currents suggest that stable, synthetic Ap4A
      analogs inhibit homomeric P2X3Rs in preference to heteromeric P2X2/3Rs. Both Ap4A
      analogs mediate clear inhibition of pain responses in both in vivo inflammation
      models. CONCLUSIONS: Stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA)
      being weak partial agonist provoke potent high-affinity desensitization-mediated
      inhibition of homomeric P2X3Rs at low concentrations. Therefore, both analogs
      demonstrate clear potential as potent analgesic agents for use in the management
      of chronic pain associated with heightened P2X3R activation.

PMID- 27030726
TI  - Computational prospecting the great viral unknown.
AB  - Bacteriophages play an important role in host-driven biological processes by
      controlling bacterial population size, horizontally transferring genes between
      hosts and expressing host-derived genes to alter host metabolism. Metagenomics
      provides the genetic basis for understanding the interplay between uncultured
      bacteria, their phage and the environment. In particular, viral metagenomes
      (viromes) are providing new insight into phage-encoded host genes (i.e. auxiliary
      metabolic genes; AMGs) that reprogram host metabolism during infection. Yet,
      despite deep sequencing efforts of viral communities, the majority of sequences
      have no match to known proteins. Reference-independent computational techniques,
      such as protein clustering, contig spectra and ecological profiling are
      overcoming these barriers to examine both the known and unknown components of
      viromes. As the field of viral metagenomics progresses, a critical assessment of
      tools is required as the majority of algorithms have been developed for analyzing
      bacteria. The aim of this paper is to offer an overview of current computational
      methodologies for virome analysis and to provide an example of reference
      independent approaches using human skin viromes. Additionally, we present methods
      to carefully validate AMGs from host contamination. Despite computational
      challenges, these new methods offer novel insights into the diversity and
      functional roles of phages in diverse environments.

PMID- 27030724
TI  - The antiallodynic action of pregabalin in neuropathic pain is independent from
      the opioid system.
AB  - BACKGROUND: Clinical management of neuropathic pain, which is pain arising as a
      consequence of a lesion or a disease affecting the somatosensory system, partly
      relies on the use of anticonvulsant drugs such as gabapentinoids. Therapeutic
      action of gabapentinoids such as gabapentin and pregabalin, which act by the
      inhibition of calcium currents through interaction with the alpha2delta-1 subunit
      of voltage-dependent calcium channels, is well documented. However, some aspects
      of the downstream mechanisms are still to be uncovered. Using behavioral,
      genetic, and pharmacological approaches, we tested whether opioid receptors are
      necessary for the antiallodynic action of acute and/or long-term pregabalin
      treatment in the specific context of neuropathic pain. RESULTS: Using the cuff
      model of neuropathic pain in mice, we show that acute pregabalin administration
      at high dose has a transitory antiallodynic action, while prolonged oral
      pregabalin treatment leads to sustained antiallodynic action, consistent with
      clinical observations. We show that pregabalin remains fully effective in MU
      opioid receptor, in delta-opioid receptor and in kappa-opioid receptor deficient
      mice, either female or male, and its antiallodynic action is not affected by
      acute naloxone. Our work also shows that long-term pregabalin treatment
      suppresses tumor necrosis factor-alpha overproduction induced by sciatic nerve
      constriction in the lumbar dorsal root ganglia. CONCLUSIONS: We demonstrate that
      neither acute nor long-term antiallodynic effect of pregabalin in a context of
      neuropathic pain is mediated by the endogenous opioid system, which differs from
      opioid treatment of pain and antidepressant treatment of neuropathic pain. Our
      data are also supportive of an impact of gabapentinoid treatment on the
      neuroimmune aspect of neuropathic pain.

PMID- 27030727
TI  - Purification, characterization and function analysis of an extracellular beta
      glucosidase from elongating stipe cell walls in Coprinopsis cinerea.
AB  - A beta-glycoside hydrolase was isolated from cell walls material in Coprinopsis
      cinerea elongating stipes. By analysis of SDS-PAGE, MALDI-TOF/TOF MS and
      substrate specificity, this enzyme was characterized as an extracellular beta
      glucosidase which is a trimer consisting of three homosubunits. beta-Glucosidase
      did not degrade beta-glucans with modified ends, whereas it hydrolyzed various
      beta-glucans with free ends and related oligosaccharides with beta-1,3-, beta-1,4
      or beta-1,6-linkages. Although this beta-glucosidase possesses
      glycosyltransferase activity on laminarioligosaccharides, it did not transfer
      glucose residues from laminaritriose to beta-glucan in stipe cell walls to
      produce larger beta-glucan molecules; instead, it caused a decrease in the
      molecular size of stipe wall beta-glucan by removing glucose. Relatively, the
      molecular size of wall beta-glucans in the elongating apical stipe was less than
      that found in the non-elongating basal stipes, and this beta-glucosidase was more
      highly expressed in the elongating apical stipe than in non-elongating basal
      regions. Therefore, we propose that beta-glucosidase functions by trimming or
      cutting the beta-glucan side chains on the beta-1,3-glucan backbone to prevent
      them from forming longer branches, keeping the wall plastic to promote diffuse
      wall growth.

PMID- 27030728
TI  - Heme sensing in Bacillus thuringiensis: a supplementary HssRS-regulated heme
      resistance system.
AB  - Several Gram-positive pathogens scavenge host-derived heme to satisfy their
      nutritional iron requirement. However, heme is a toxic molecule capable of
      damaging the bacterial cell. Gram-positive pathogens within the phylum Firmicutes
      overcome heme toxicity by sensing heme through HssRS, a two-component system that
      regulates the heme detoxification transporter HrtAB. Here we show that heme
      sensing by HssRS and heme detoxification by HrtAB occur in the insect pathogen
      Bacillus thuringiensis We find that in B. thuringiensis, HssRS directly regulates
      an operon, hrmXY, encoding hypothetical membrane proteins that are not found in
      other Firmicutes with characterized HssRS and HrtAB systems. This novel HssRS
      regulated operon or its orthologs BMB171_c3178 and BMB171_c3330 are required for
      maximal heme resistance. Furthermore, the activity of HrmXY is not dependent on
      expression of HrtAB. These results suggest that B. thuringiensis senses heme
      through HssRS and induces expression of separate membrane-localized systems
      capable of overcoming different aspects of heme toxicity.

PMID- 27030730
TI  - Functional status in patients with medically unexplained physical symptoms:
      Coping styles and their relationship with depression and anxiety.
AB  - This study examined how coping styles are related to functional status in
      patients with medically unexplained physical symptoms and to what extent
      depression and anxiety account for this relationship. In 90 Dutch adult patients
      presenting medically unexplained physical symptoms, coping styles, health-related
      functional status, anxiety, and depression were measured. Multiple regression
      analyses and mediation analysis showed that coping styles were directly and
      indirectly related to functional status. In this relationship, depression and
      anxiety played an important role. The findings highlight the relevance of
      addressing coping styles, depression, and anxiety when targeting the functional
      status of patients with medically unexplained physical symptoms in clinical
      practice.

PMID- 27030731
TI  - The effect of psychological capital between work-family conflict and job burnout
      in Chinese university teachers: Testing for mediation and moderation.
AB  - In this study, we investigated the relationship between work-family conflict and
      job burnout as well as the potential mediation/moderation effects of
      psychological capital. Participants were 357 university teachers who completed a
      questionnaire packet containing a work-family conflict scale, psychological
      capital questionnaire, and Maslach Burnout Inventory-General survey. According to
      the results, work-family conflict and psychological capital were both
      significantly correlated with job burnout. In addition, psychological capital
      cannot mediate-but can moderate-the relationship between work-family conflict and
      job burnout. Taken together, our findings shed light on the psychological capital
      underlying the association of work-family conflict and job burnout.

PMID- 27030732
TI  - Improving Neurodevelopmental Care for Young Children in Primary Care Services.

PMID- 27030733
TI  - Evolution of the APETALA2 Gene Lineage in Seed Plants.
AB  - Gene duplication is a fundamental source of functional evolutionary change and
      has been associated with organismal diversification and the acquisition of novel
      features. The APETALA2/ETHYLENE RESPONSIVE ELEMENT-BINDING FACTOR (AP2/ERF) genes
      are exclusive to vascular plants and have been classified into the AP2-like and
      ERF-like clades. The AP2-like clade includes the AINTEGUMENTA (ANT) and the
      euAPETALA2 (euAP2) genes, both regulated by miR172 Arabidopsis has two paralogs
      in the euAP2 clade, namely APETALA2 (AP2) and TARGET OF EAT3 (TOE3) that control
      flowering time, meristem determinacy, sepal and petal identity and fruit
      development. euAP2 genes are likely functionally divergent outside Brassicaceae,
      as they control fruit development in tomato, and regulate inflorescence
      meristematic activity in maize. We studied the evolution and expression patterns
      of euAP2/TOE3 genes to assess large scale and local duplications and evaluate
      protein motifs likely related with functional changes across seed plants. We
      sampled euAP2/TOE3 genes from vascular plants and have found three major
      duplications and a few taxon-specific duplications. Here, we report conserved and
      new motifs across euAP2/TOE3 proteins and conclude that proteins predating the
      Brassicaceae duplication are more similar to AP2 than TOE3. Expression data show
      a shift from restricted expression in leaves, carpels, and fruits in non-core
      eudicots and asterids to a broader expression of euAP2 genes in leaves, all
      floral organs and fruits in rosids. Altogether, our data show a functional trend
      where the canonical A-function (sepal and petal identity) is exclusive to
      Brassicaceae and it is likely not maintained outside of rosids.

PMID- 27030734
TI  - Receptive field size, chemical and thermal responses, and fiber conduction
      velocity of rat chorda tympani geniculate ganglion neurons.
AB  - Afferent chorda tympani (CT) fibers innervating taste and somatosensory receptors
      in fungiform papillae have neuron cell bodies in the geniculate ganglion (GG).
      The GG/CT fibers branch in the tongue to innervate taste buds in several
      fungiform papillae. To investigate receptive field characteristics of GG/CT
      neurons, we recorded extracellular responses from GG cells to application of
      chemical and thermal stimuli. Receptive field size was mapped by electrical
      stimulation of individual fungiform papillae. Response latency to electrical
      stimulation was used to determine fiber conduction velocity. Responses of GG
      neurons to lingual application of stimuli representing four taste qualities, and
      water at 4 degrees C, were used to classify neuron response properties. Neurons
      classified as SALT, responding only to NaCl and NH4Cl, had a mean receptive field
      size of six papillae. Neurons classified as OTHER responded to salts and other
      chemical stimuli and had smaller mean receptive fields of four papillae. Neurons
      that responded to salts and cold stimuli, classified as SALT/THERMAL, and neurons
      responding to salts, other chemical stimuli and cold, classified as
      OTHER/THERMAL, had mean receptive field sizes of six and five papillae,
      respectively. Neurons responding only to cold stimuli, categorized as THERMAL,
      had receptive fields of one to two papillae located at the tongue tip. Based on
      conduction velocity most of the neurons were classified as C fibers. Neurons with
      large receptive fields had higher conduction velocities than neurons with small
      receptive fields. These results demonstrate that GG neurons can be distinguished
      by receptive field size, response properties and afferent fiber conduction
      velocity derived from convergent input of multiple taste organs.

PMID- 27030735
TI  - The functional organization of human epileptic hippocampus.
AB  - The function and connectivity of human brain is disrupted in epilepsy. We
      previously reported that the region of epileptic brain generating focal seizures,
      i.e., the seizure onset zone (SOZ), is functionally isolated from surrounding
      brain regions in focal neocortical epilepsy. The modulatory effect of behavioral
      state on the spatial and spectral scales over which the reduced functional
      connectivity occurs, however, is unclear. Here we use simultaneous sleep staging
      from scalp EEG with intracranial EEG recordings from medial temporal lobe to
      investigate how behavioral state modulates the spatial and spectral scales of
      local field potential synchrony in focal epileptic hippocampus. The local field
      spectral power and linear correlation between adjacent electrodes provide
      measures of neuronal population synchrony at different spatial scales, ~1 and 10
      mm, respectively. Our results show increased connectivity inside the SOZ and low
      connectivity between electrodes in SOZ and outside the SOZ. During slow-wave
      sleep, we observed decreased connectivity for ripple and fast ripple frequency
      bands within the SOZ at the 10 mm spatial scale, while the local synchrony
      remained high at the 1 mm spatial scale. Further study of these phenomena may
      prove useful for SOZ localization and help understand seizure generation, and the
      functional deficits seen in epileptic eloquent cortex.

PMID- 27030736
TI  - DREADD-induced activation of subfornical organ neurons stimulates thirst and salt
      appetite.
AB  - The subfornical organ (SFO) plays a pivotal role in body fluid homeostasis
      through its ability to integrate neurohumoral signals and subsequently alter
      behavior, neuroendocrine function, and autonomic outflow. The purpose of the
      present study was to evaluate whether selective activation of SFO neurons using
      virally mediated expression of Designer Receptors Exclusively Activated by
      Designer Drugs (DREADDs) stimulated thirst and salt appetite. Male C57BL/6 mice
      (12-15 wk) received an injection of rAAV2-CaMKII-HA-hM3D(Gq)-IRES-mCitrine
      targeted at the SFO. Two weeks later, acute injection of clozapine N-oxide (CNO)
      produced dose-dependent increases in water intake of mice with DREADD expression
      in the SFO. CNO also stimulated the ingestion of 0.3 M NaCl. Acute injection of
      CNO significantly increased the number of Fos-positive nuclei in the SFO of mice
      with robust DREADD expression. Furthermore, in vivo single-unit recordings
      demonstrate that CNO significantly increases the discharge frequency of both ANG
      II- and NaCl-responsive neurons. In vitro current-clamp recordings confirm that
      bath application of CNO produces a significant membrane depolarization and
      increase in action potential frequency. In a final set of experiments, chronic
      administration of CNO approximately doubled 24-h water intake without an effect
      on salt appetite. These findings demonstrate that DREADD-induced activation of
      SFO neurons stimulates thirst and that DREADDs are a useful tool to acutely or
      chronically manipulate neuronal circuits influencing body fluid homeostasis.

PMID- 27030737
TI  - Modular organization of the multipartite central pattern generator for turtle
      rostral scratch: knee-related interneurons during deletions.
AB  - Central pattern generators (CPGs) are neuronal networks in the spinal cord that
      generate rhythmic patterns of motor activity in the absence of movement-related
      sensory feedback. For many vertebrate rhythmic behaviors, CPGs generate normal
      patterns of motor neuron activities as well as variations of the normal patterns,
      termed deletions, in which bursts in one or more motor nerves are absent from one
      or more cycles of the rhythm. Prior work with hip-extensor deletions during
      turtle rostral scratch supports hypotheses of hip-extensor interneurons in a hip
      extensor module and of hip-flexor interneurons in a hip-flexor module. We present
      here single-unit interneuronal recording data that support hypotheses of knee
      extensor interneurons in a knee-extensor module and of knee-flexor interneurons
      in a knee-flexor module. Members of knee-related modules are not members of hip
      related modules and vice versa. These results in turtle provide experimental
      support at the single-unit interneuronal level for the organizational concept
      that the rostral-scratch CPG for the turtle hindlimb is multipartite, that is,
      composed of more than two modules. This work, when combined with experimental and
      computational work in other vertebrates, does not support the classical view that
      the vertebrate limb CPG is bipartite with only two modules, one controlling all
      the flexors of the limb and the other controlling all the extensors of the limb.
      Instead, these results support the general principle that spinal CPGs are
      multipartite.

PMID- 27030738
TI  - The sequential encoding of competing action goals involves dynamic restructuring
      of motor plans in working memory.
AB  - Recent neural and behavioral findings provide support for the influential idea
      that in situations in which multiple action options are presented simultaneously,
      we prepare action plans for each competing option before deciding between and
      executing one of those plans. However, in natural, everyday environments, our
      available action options frequently change from one moment to the next, and there
      is often uncertainty as to whether additional options will become available
      before having to select a particular course of action. Here, with the use of a
      target-directed reaching task, we show that in this situation, the brain
      specifies a competing action for each new, sequentially presented potential
      target and that recently formed action plans can be revisited and updated so as
      to conform with separate, more newly developed, plans. These findings indicate
      that the brain forms labile motor plans for sequentially arising target options
      that can be flexibly restructured to accommodate new motor plans.

PMID- 27030740
TI  - Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease.
AB  - McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase
      deficiency, which leads to impaired glycogen breakdown. We investigated how
      myophosphorylase deficiency affects muscle physiology, morphology, and glucose
      metabolism in 20-week-old McArdle mice and compared the findings to those in
      McArdle disease patients. Muscle contractions in the McArdle mice were affected
      by structural degeneration due to glycogen accumulation, and glycolytic muscles
      fatigued prematurely, as occurs in the muscles of McArdle disease patients.
      Homozygous McArdle mice showed muscle fiber disarray, variations in fiber size,
      vacuoles, and some internal nuclei associated with cytosolic glycogen
      accumulation and ongoing regeneration; structural damage was seen only in a
      minority of human patients. Neither liver nor brain isoforms of glycogen
      phosphorylase were upregulated in muscles, thus providing no substitution for the
      missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were
      invariably more damaged than the quadriceps muscles. This may relate to a 7-fold
      higher level of myophosphorylase in TA compared to quadriceps in wild-type mice
      and suggests higher glucose turnover in the TA. Thus, despite differences, the
      mouse model of McArdle disease shares fundamental physiological and clinical
      features with the human disease and could be used for studies of pathogenesis and
      development of therapies. 

PMID- 27030739
TI  - Network feedback regulates motor output across a range of modulatory neuron
      activity.
AB  - Modulatory projection neurons alter network neuron synaptic and intrinsic
      properties to elicit multiple different outputs. Sensory and other inputs elicit
      a range of modulatory neuron activity that is further shaped by network feedback,
      yet little is known regarding how the impact of network feedback on modulatory
      neurons regulates network output across a physiological range of modulatory
      neuron activity. Identified network neurons, a fully described connectome, and a
      well-characterized, identified modulatory projection neuron enabled us to address
      this issue in the crab (Cancer borealis) stomatogastric nervous system. The
      modulatory neuron modulatory commissural neuron 1 (MCN1) activates and modulates
      two networks that generate rhythms via different cellular mechanisms and at
      distinct frequencies. MCN1 is activated at rates of 5-35 Hz in vivo and in vitro.
      Additionally, network feedback elicits MCN1 activity time-locked to motor
      activity. We asked how network activation, rhythm speed, and neuron activity
      levels are regulated by the presence or absence of network feedback across a
      physiological range of MCN1 activity rates. There were both similarities and
      differences in responses of the two networks to MCN1 activity. Many parameters in
      both networks were sensitive to network feedback effects on MCN1 activity.
      However, for most parameters, MCN1 activity rate did not determine the extent to
      which network output was altered by the addition of network feedback. These data
      demonstrate that the influence of network feedback on modulatory neuron activity
      is an important determinant of network output and feedback can be effective in
      shaping network output regardless of the extent of network modulation.

PMID- 27030741
TI  - A Neurogenic Perspective of Sarcopenia: Time Course Study of Sciatic Nerves From
      Aging Mice.
AB  - To elucidate the neural basis for age-related sarcopenia, we quantified
      morphologic and molecular changes within sciatic nerves of aging male and female
      C57BL/6J mice aged between 3 and 27 months using immunoblotting,
      immunohistochemistry, and electron microscopy. Protein analyses by immunoblotting
      of nerves of male mice aged 4, 15, 18, 22, and 24 months showed increased levels
      of heavy chain SMI-32-positive neurofilaments, vimentin, tau5, choline
      acetyltransferase (ChAT), and p62 by 18-22 months. Similar protein increases were
      seen in 26-month-old compared with 3-month-old female mice. Immunostaining of
      longitudinal sections of old (27-month-old) male sciatic nerves revealed intense
      staining for tau5 and p62 that was increased compared with that at 3 months, but
      there were decreased numbers of axon profiles stained for ChAT or isolectin B4
      (motor and sensory axons, respectively). Ultrastructural analysis revealed
      electron-dense aggregates within axons in peripheral nerves of old male mice; the
      proportion of axons that contained aggregates more than doubled between 15 and 27
      months. Overall, the observed age-related accumulation of many proteins from
      about 18 months of age onward suggests impaired mechanisms for axonal transport
      and protein turnover. These peripheral nerve changes may contribute to the
      morphological and functional muscle deficits associated with sarcopenia. 

PMID- 27030742
TI  - Glioma Stem Cells but Not Bulk Glioma Cells Upregulate IL-6 Secretion in
      Microglia/Brain Macrophages via Toll-like Receptor 4 Signaling.
AB  - Peripheral macrophages and resident microglia constitute the dominant glioma
      infiltrating cells. The tumor induces an immunosuppressive and tumor-supportive
      phenotype in these glioma-associated microglia/brain macrophages (GAMs). A
      subpopulation of glioma cells acts as glioma stem cells (GSCs). We explored the
      interaction between GSCs and GAMs. Using CD133 as a marker of stemness, we
      enriched for or deprived the mouse glioma cell line GL261 of GSCs by fluorescence
      activated cell sorting (FACS). Over the same period of time, 100 CD133(+ )GSCs
      had the capacity to form a tumor of comparable size to the ones formed by 10,000
      CD133(-) GL261 cells. In IL-6(-/-) mice, only tumors formed by CD133(+ )cells
      were smaller compared with wild type. After stimulation of primary cultured
      microglia with medium from CD133-enriched GL261 glioma cells, we observed an
      selective upregulation in microglial IL-6 secretion dependent on Toll-like
      receptor (TLR) 4. Our results show that GSCs, but not the bulk glioma cells,
      initiate microglial IL-6 secretion via TLR4 signaling and that IL-6 regulates
      glioma growth by supporting GSCs. Using human glioma tissue, we could confirm the
      finding that GAMs are the major source of IL-6 in the tumor context. 

PMID- 27030743
TI  - Experimental Induction of Cerebral Aneurysms by Developmental Low Copper Diet.
AB  - Optimal models are needed to understand the pathophysiology of human cerebral
      aneurysms (CA). We investigated the development of experimental CA by decreasing
      the activity of lysyl oxidases by dietary copper deficiency from the time of
      gestation and then augmenting vascular stress by angiotensin II infusion in
      adulthood. Rats were fed copper-free, low-copper, or normal diets at different
      time periods from gestation to adulthood. The incidences of CAs were evaluated
      and autopsies performed to determine the coexistence of cardiovascular diseases.
      A copper-free diet from gestation was associated with high mortality rates
      (79.1%) resulting from rupture of ascending aorta aneurysms; a low-copper diet
      led to acceptable mortality rates (13.6%) and produced CAs and subarachnoid
      hemorrhage in 46.4% and 3.6% of animals, respectively. Higher proportions of CAs
      (up to 33.3%) in the rats primed for copper deficiency from gestation ruptured
      following angiotensin II infusion from adulthood. Gene expression array analyses
      of the CAs indicated that genes involving extracellular matrix and vascular
      remodeling were altered in this model. This model enables future research to
      understand the entire pathogenetic basis of CA development and rupture in
      association with systemic vasculopathies. 

PMID- 27030745
TI  - ERRATA.

PMID- 27030747
TI  - Plant-to-Plant Movement of Striacosta albicosta (Lepidoptera: Noctuidae) and
      Spodoptera frugiperda (Lepidoptera: Noctuidae) in Maize (Zea mays).
AB  - Integrated pest management (IPM) and insect resistance management (IRM) in
      various cropping systems demand a comprehensive understanding of insect behavior.
      Among the needed information is basic charaterizations of larval movement and
      dispersion of some insect-pests, such as the noctuidsStriacosta albicosta(Smith)
      andSpodoptera frugiperda(J.E. Smith). We investigated the plant-to-plant movement
      of western bean cutworm and fall armyworm larvae in field of maize. Experiments
      onS. albicostawere conducted between 2008 and 2010. A main study with this pest
      was performed in 2012 in a randomized complete block design (RCBD) with nine
      replications. AnS. frugiperdastudy was performed in 2013 in an RCBD with eight
      replications. The plant- to-plant movement and larval survival were measured in
      plots with maize nontoxic to the insects. The larval survival ofS.
      albicostapresented high variety throughout the years. AlthoughS.
      frugiperdasurvival was relatively low during 2013, it did not compromise the
      larval assessment. Larvae of both species dispersed governed by nondirectional
      sensory information, and presented aggregated and symmetrical distribution;
      however, fall armyworm remained nearer the release point. These results may help
      the IPM components, such as scouting and economic threshold, as well as the
      implementation of refuge and seed mixture strategies for IRM.

PMID- 27030744
TI  - IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases.
AB  - The TH17 immune response has a central role in the pathogenesis of autoimmune
      diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator
      of diseases such as human and experimental crescentic GN. However, the relative
      importance of additional TH17 effector cytokines, including IL-17F, in immune
      mediated tissue injury remains to be fully elucidated. Here, using a mouse model
      of acute crescentic GN (nephrotoxic nephritis), we identified CD4+ T cells and
      gammadelta T cells as the major cellular source of IL-17F in the inflamed kidney.
      Interventional studies using IL-17F gene-deficient mice, IL-17F-neutralizing
      antibodies, and adoptive transfer experiments into Rag1-/- mice demonstrated that
      CD4+ T cell-derived IL-17F drives renal tissue injury in acute crescentic GN.
      Notably, IL-17F-deficient nephritic mice had fewer renal infiltrating neutrophils
      than wild-type nephritic mice, and neutrophil depletion did not affect the course
      of GN in IL-17F-deficient mice. Moreover, in the chronic model of pristane
      induced SLE, IL-17F-deficient mice developed less severe disease than wild-type
      mice, with respect to survival and renal injury. Finally, we show that IL-17F
      induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in
      kidney cells. The finding that IL-17F has a nonredundant function in the
      development of renal tissue injury in experimental GN might be of great
      importance for the development of anti-IL-17 cytokine therapies in TH17-mediated
      human autoimmune diseases.

PMID- 27030748
TI  - Management of Megacopta cribraria (Hemiptera: Plataspidae) at Different Stages of
      Soybean (Fabales: Fabaceae) Development.
AB  - The invasive plataspidMegacopta cribraria(F.) is now distributed throughout much
      of the southeastern United States. While it readily feeds and develops on the
      invasive weed kudzu,Puereria montana(Loureiro) Merrill var.lobata(Willdenow),M.
      cribrariais an economic pest of soybean,Glycine max(L.) Merrill. Differences in
      the susceptibility of soybean toM. cribraria-induced yield reductions based on
      plant phenology were assessed using two experimental protocols in Georgia, North
      Carolina, and South Carolina from 2011 to 2013 in which soybeans were protected
      fromM. cribrariausing insecticides during different stages of plant phenology. In
      the first protocol, where insecticide applications were initiated at
      progressively later stages in soybean development depending on treatment, yields
      in the untreated plots were reduced by an average of 13% compared with plots that
      were protected beginning at full flowering (R2). Soybean plots that were
      protected beginning at 4 wk after full flowering or earlier did not suffer yield
      reductions fromM. cribraria In the second protocol, where insecticide
      applications began at R2 and were discontinued at progressively later stages in
      soybean development depending on treatment, yields in the untreated plots were
      reduced by an average of 12% compared with plots that were protected until 8 wk
      after R2. Plots in which protection was discontinued beginning at 4 wk after full
      flowering or later did not suffer yield reductions. The period from two to 6 wk
      after R2 (generally coinciding with pod and seed development - stages R3-R5) was
      identified as critical for management ofM. cribraria.

PMID- 27030749
TI  - Effect of Temperature on the Fecundity and Longevity of Ascotis selenaria
      (Lepidoptera: Geometridae): Developing an Oviposition Model.
AB  - The fecundity and longevity ofAscotis selenaria(Denis & Schiffermuller 1775)
      female adults were examined at constant temperatures ranging from 13-35 degrees
      C. Adult longevity decreased as the temperature increased and ranged from 26.2 d
      at 13.1 degrees C to 5.2 d at 34.3 degrees C. The maximum observed fecundity ofA.
      selenariawas 2,420 eggs per female at 19.4 degrees C, which decreased to ca 100
      eggs per female at 34.3 degrees C. Female adult aging rates (one per median
      longevity) were well described by a sigmoid equation in the range of 13-35
      degrees C used to calculate the physiological age of adults. The relationship
      between total fecundity and temperature was well described by an extreme value
      function. Age-specific cumulative oviposition rate and age-specific survival rate
      curve were fitted to a three-parameter Weibull function. An oviposition model
      forA. selenariawas developed using the estimated three temperature-dependent
      submodels: total fecundity, age-specific cumulative oviposition, and age-specific
      survival rate models. The oviposition model was simulated using pheromone catches
      ofA. selenariafemales as input value. Simulated egg populations were subjected to
      egg stage emergence model to project first-instar populations. Overall, the
      output of our simulation described the field occurrence pattern ofA.
      selenariafirst-instar populations in 2009 and 2010.

PMID- 27030750
TI  - Cognitive Processing Involves Dynamic Reorganization of the Whole-Brain Network's
      Functional Community Structure.

PMID- 27030751
TI  - Multiplexed Population Coding of Stimulus Properties by Leech Mechanosensory
      Cells.
AB  - Sensory coding has long been discussed in terms of a dichotomy between spike
      timing and rate coding. However, recent studies found that in primate
      mechanoperception and other sensory systems, spike rates and timing of cell
      populations complement each other. They simultaneously carry information about
      different stimulus properties in a multiplexed way. Here, we present evidence for
      multiplexed encoding of tactile skin stimulation in the tiny population of leech
      mechanoreceptors, consisting of only 10 cells of two types with overlapping
      receptive fields. Each mechanoreceptor neuron of the leech varies spike count and
      response latency to both touch intensity and location, leading to ambiguous
      responses to different stimuli. Nevertheless, three different stimulus estimation
      techniques consistently reveal that the neuronal population allows reliable
      decoding of both stimulus properties. For the two mechanoreceptor types, the
      transient responses of T (touch) cells and the sustained responses of P
      (pressure) cells, the relative timing of the first spikes of two mechanoreceptors
      encodes stimulus location, whereas summed spike counts represent touch intensity.
      Differences between the cell types become evident in responses to combined
      stimulus properties. The best estimation performance for stimulus location is
      obtained from the relative first spike timing of the faster and temporally more
      precise T cells. Simultaneously, the sustained responses of P cells indicate
      touch intensity by summed spike counts and stimulus duration by the duration of
      spike responses. The striking similarities of these results with previous
      findings on primate mechanosensory afferents suggest multiplexed population
      coding as a general principle of somatosensation. SIGNIFICANCE STATEMENT:
      Multiplexing, the simultaneous encoding of different stimulus properties by
      distinct neuronal response features, has recently been suggested as a mechanism
      used in several sensory systems, including primate somatosensation. While a
      rigorous experimental verification of the multiplexing hypothesis is difficult to
      accomplish in a complex vertebrate system, it is feasible for a small population
      of individually characterized leech neurons. Monitoring the responses of all four
      mechanoreceptors innervating a patch of skin revealed striking similarities
      between touch encoding in the primate and the leech: summed spike counts
      represent stimulus intensity, whereas relative timing of first spikes encodes
      stimulus location. These findings suggest that multiplexed population coding is a
      general mechanism of touch encoding common to species as different as man and
      worm.

PMID- 27030752
TI  - Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and
      Impairs Gamma Oscillations in the Prefrontal Cortex.
AB  - The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a
      serine/threonine kinase involved in neuronal differentiation and synaptic
      plasticity and a major candidate of Down syndrome brain alterations and cognitive
      deficits. DYRK1A is strongly expressed in the cerebral cortex, and its
      overexpression leads to defective cortical pyramidal cell morphology, synaptic
      plasticity deficits, and altered excitation/inhibition balance. These previous
      observations, however, do not allow predicting how the behavior of the prefrontal
      cortex (PFC) network and the resulting properties of its emergent activity are
      affected. Here, we integrate functional, anatomical, and computational data
      describing the prefrontal network alterations in transgenic mice
      overexpressingDyrk1A(TgDyrk1A). Usingin vivoextracellular recordings, we show
      decreased firing rate and gamma frequency power in the prefrontal network of
      anesthetized and awakeTgDyrk1Amice. Immunohistochemical analysis identified a
      selective reduction of vesicular GABA transporter punctae on parvalbumin positive
      neurons, without changes in the number of cortical GABAergic neurons in the PFC
      ofTgDyrk1Amice, which suggests that selective disinhibition of parvalbumin
      interneurons would result in an overinhibited functional network. Using a
      conductance-based computational model, we quantitatively demonstrate that this
      alteration could explain the observed functional deficits including decreased
      gamma power and firing rate. Our results suggest that dysfunction of cortical
      fast-spiking interneurons might be central to the pathophysiology of Down
      syndrome. SIGNIFICANCE STATEMENT: DYRK1Ais a major candidate gene in Down
      syndrome. Its overexpression results into altered cognitive abilities, explained
      by defective cortical microarchitecture and excitation/inhibition imbalance. An
      open question is how these deficits impact the functionality of the prefrontal
      cortex network. Combining functional, anatomical, and computational approaches,
      we identified decreased neuronal firing rate and deficits in gamma frequency in
      the prefrontal cortices of transgenic mice overexpressingDyrk1A We also
      identified a reduction of vesicular GABA transporter punctae specifically on
      parvalbumin positive interneurons. Using a conductance-based computational model,
      we demonstrate that this decreased inhibition on interneurons recapitulates the
      observed functional deficits, including decreased gamma power and firing rate.
      Our results suggest that dysfunction of cortical fast-spiking interneurons might
      be central to the pathophysiology of Down syndrome.

PMID- 27030753
TI  - Complementary Functional Organization of Neuronal Activity Patterns in the
      Perirhinal, Lateral Entorhinal, and Medial Entorhinal Cortices.
AB  - It is commonly conceived that the cortical areas of the hippocampal region are
      functionally divided into the perirhinal cortex (PRC) and the lateral entorhinal
      cortex (LEC), which selectively process object information; and the medial
      entorhinal cortex (MEC), which selectively processes spatial information.
      Contrary to this notion, in rats performing a task that demands both object and
      spatial information processing, single neurons in PRC, LEC, and MEC, including
      those in both superficial and deep cortical areas and in grid, border, and head
      direction cells of MEC, have a highly similar range of selectivity to object and
      spatial dimensions of the task. By contrast, representational similarity analysis
      of population activity reveals a key distinction in the organization of
      information in these areas, such that PRC and LEC populations prioritize object
      over location information, whereas MEC populations prioritize location over
      object information. These findings bring to the hippocampal system a growing
      emphasis on population analyses as a powerful tool for characterizing neural
      representations supporting cognition and memory. SIGNIFICANCE STATEMENT: Contrary
      to the common view that brain regions in the "what" and "where" streams
      distinctly process object and spatial cues, respectively, we found that both
      streams encode both object and spatial information but distinctly organize
      memories for objects and space. Specifically, perirhinal cortex and lateral
      entorhinal cortex represent objects and, within the object-specific
      representations, the locations where they occur. Conversely, medial entorhinal
      cortex represents relevant locations and, within those spatial representations,
      the objects that occupy them. Furthermore, these findings reach beyond simple
      notions of perirhinal cortex and lateral entorhinal cortex neurons as object
      detectors and MEC neurons as position detectors, and point to a more complex
      organization of memory representations within the medial temporal lobe system.

PMID- 27030754
TI  - Thalamic and Entorhinal Network Activity Differently Modulates the Functional
      Development of Prefrontal-Hippocampal Interactions.
AB  - Precise information flow during mnemonic and executive tasks requires the
      coactivation of adult prefrontal and hippocampal networks in oscillatory rhythms.
      This interplay emerges early in life, most likely as an anticipatory template of
      later cognitive performance. At neonatal age, hippocampal theta bursts drive the
      generation of prefrontal theta-gamma oscillations. In the absence of direct
      reciprocal interactions, the question arises of which feedback mechanisms control
      the early entrainment of prefrontal-hippocampal networks. Here, we demonstrate
      that prefrontal-hippocampal activity couples with discontinuous theta
      oscillations and neuronal firing in both lateral entorhinal cortex and ventral
      midline thalamic nuclei of neonatal rats. However, these two brain areas have
      different contributions to the neonatal long-range communication. The entorhinal
      cortex mainly modulates the hippocampal activity via direct axonal projections.
      In contrast, thalamic theta bursts are controlled by the prefrontal cortex via
      mutual projections and contribute to hippocampal activity. Thus, the neonatal
      prefrontal cortex modulates the level of hippocampal activation by directed
      interactions with the ventral midline thalamus. Similar to the adult task-related
      communication, theta-band activity ensures the feedback control of long-range
      coupling in the developing brain. SIGNIFICANCE STATEMENT: Memories are encoded by
      finely tuned interactions within large-scale neuronal networks. This cognitive
      performance is not inherited, but progressively matures in relationship with the
      establishment of long-range coupling in the immature brain. The hippocampus
      initiates and unidirectionally drives the oscillatory entrainment of neonatal
      prefrontal cortex, yet feedback interactions that precisely control this early
      communication are still unresolved. Here, we identified distinct roles of
      entorhinal cortex and ventral midline thalamus for the functional development of
      prefrontal-hippocampal interactions. While entorhinal oscillations modulate the
      hippocampal activity by timing the neuronal firing via monosynaptic afferents,
      thalamic nuclei act as a relay station routing prefrontal activation back to
      hippocampus. Understanding the mechanisms of network maturation represents the
      prerequisite for assessing circuit dysfunction in neurodevelopmental disorders.

PMID- 27030755
TI  - Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice
      with Impaired Met Activity.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic
      variants, susceptibility alleles, and environmental perturbations. The autism
      associated geneMETtyrosine kinase has been implicated in many behavioral domains
      and endophenotypes of autism, including abnormal neural signaling in human
      sensory cortex. We investigated somatosensory thalamocortical synaptic
      communication in mice deficient in Met activity in cortical excitatory neurons to
      gain insights into aberrant somatosensation characteristic of ASD. The ratio of
      excitation to inhibition is dramatically increased due to decreased postsynaptic
      GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of
      mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild
      type mice, insulin failed to increase GABAAreceptor-mediated response in the
      barrel cortex of mice with compromised Met signaling. Thus, lacking insulin
      effects may be a risk factor in ASD pathogenesis. SIGNIFICANCE STATEMENT: A
      proposed common cause of neurodevelopmental disorders is an imbalance in
      excitatory neural transmission, provided by the glutamatergic neurons, and the
      inhibitory signals from the GABAergic interneurons. Many genes associated with
      autism spectrum disorders impair synaptic transmission in the expected cell type.
      Previously, inactivation of the autism-associated Met tyrosine kinase receptor in
      GABAergic interneurons led to decreased inhibition. In thus report, decreased Met
      signaling in glutamatergic neurons had no effect on excitation, but decimated
      inhibition. Further experiments indicate that loss of Met activity downregulates
      GABAAreceptors on glutamatergic neurons in an insulin independent manner. These
      data provide a new mechanism for the loss of inhibition and subsequent abnormal
      excitation/inhibition balance and potential molecular candidates for treatment or
      prevention.

PMID- 27030756
TI  - Reversal of Alcohol-Induced Dysregulation in Dopamine Network Dynamics May Rescue
      Maladaptive Decision-making.
AB  - Alcohol is the most commonly abused substance among adolescents, promoting the
      development of substance use disorders and compromised decision-making in
      adulthood. We have previously demonstrated, with a preclinical model in rodents,
      that adolescent alcohol use results in adult risk-taking behavior that positively
      correlates with phasic dopamine transmission in response to risky options, but
      the underlying mechanisms remain unknown. Here, we show that adolescent alcohol
      use may produce maladaptive decision-making through a disruption in dopamine
      network dynamics via increased GABAergic transmission within the ventral
      tegmental area (VTA). Indeed, we find that increased phasic dopamine signaling
      after adolescent alcohol use is attributable to a midbrain circuit, including the
      input from the pedunculopontine tegmentum to the VTA. Moreover, we demonstrate
      that VTA dopamine neurons from adult rats exhibit enhanced IPSCs after adolescent
      alcohol exposure corresponding to decreased basal dopamine levels in adulthood
      that negatively correlate with risk-taking. Building on these findings, we
      develop a model where increased inhibitory tone on dopamine neurons leads to a
      persistent decrease in tonic dopamine levels and results in a potentiation of
      stimulus-evoked phasic dopamine release that may drive risky choice behavior.
      Based on this model, we take a pharmacological approach to the reversal of risk
      taking behavior through normalization of this pattern in dopamine transmission.
      These results isolate the underlying circuitry involved in alcohol-induced
      maladaptive decision-making and identify a novel therapeutic target. SIGNIFICANCE
      STATEMENT: One of the primary problems resulting from chronic alcohol use is
      persistent, maladaptive decision-making that is associated with ongoing addiction
      vulnerability and relapse. Indeed, studies with the Iowa Gambling Task, a
      standard measure of risk-based decision-making, have reliably shown that alcohol
      dependent individuals make riskier, more maladaptive choices than nondependent
      individuals, even after periods of prolonged abstinence. Using a preclinical
      model, in the current work, we identify a selective disruption in dopamine
      network dynamics that may promote maladaptive decision-making after chronic
      adolescent alcohol use and demonstrate its pharmacological reversal in adulthood.
      Together, these results highlight a novel neural mechanism underlying heightened
      risk-taking behavior in alcohol-dependent individuals and provide a potential
      therapeutic target for further investigation.

PMID- 27030757
TI  - An Adenosine-Mediated Glial-Neuronal Circuit for Homeostatic Sleep.
AB  - Sleep homeostasis reflects a centrally mediated drive for sleep, which increases
      during waking and resolves during subsequent sleep. Here we demonstrate that mice
      deficient for glial adenosine kinase (AdK), the primary metabolizing enzyme for
      adenosine (Ado), exhibit enhanced expression of this homeostatic drive by three
      independent measures: (1) increased rebound of slow-wave activity; (2) increased
      consolidation of slow-wave sleep; and (3) increased time constant of slow-wave
      activity decay during an average slow-wave sleep episode, proposed and validated
      here as a new index for homeostatic sleep drive. Conversely, mice deficient for
      the neuronal adenosine A1 receptor exhibit significantly decreased sleep drive as
      judged by these same indices. Neuronal knock-out of AdK did not influence
      homeostatic sleep need. Together, these findings implicate a glial-neuronal
      circuit mediated by intercellular Ado, controlling expression of homeostatic
      sleep drive. Because AdK is tightly regulated by glial metabolic state, our
      findings suggest a functional link between cellular metabolism and sleep
      homeostasis. SIGNIFICANCE STATEMENT: The work presented here provides evidence
      for an adenosine-mediated regulation of sleep in response to waking (i.e.,
      homeostatic sleep need), requiring activation of neuronal adenosine A1 receptors
      and controlled by glial adenosine kinase. Adenosine kinase acts as a highly
      sensitive and important metabolic sensor of the glial ATP/ADP and AMP ratio
      directly controlling intracellular adenosine concentration. Glial equilibrative
      adenosine transporters reflect the intracellular concentration to the
      extracellular milieu to activate neuronal adenosine receptors. Thus, adenosine
      mediates a glial-neuronal circuit linking glial metabolic state to neural
      expressed sleep homeostasis. This indicates a metabolically related function(s)
      for this glial-neuronal circuit in the buildup and resolution of our need to
      sleep and suggests potential therapeutic targets more directly related to sleep
      function.

PMID- 27030758
TI  - Homeostatic Activity-Dependent Tuning of Recurrent Networks for Robust
      Propagation of Activity.
AB  - Developing neuronal networks display spontaneous bursts of action potentials that
      are necessary for circuit organization and tuning. While spontaneous activity has
      been shown to instruct map formation in sensory circuits, it is unknown whether
      it plays a role in the organization of motor networks that produce rhythmic
      output. Using computational modeling, we investigate how recurrent networks of
      excitatory and inhibitory neuronal populations assemble to produce robust
      patterns of unidirectional and precisely timed propagating activity during
      organism locomotion. One example is provided by the motor network
      inDrosophilalarvae, which generates propagating peristaltic waves of muscle
      contractions during crawling. We examine two activity-dependent models, which
      tune weak network connectivity based on spontaneous activity patterns: a Hebbian
      model, where coincident activity in neighboring populations strengthens
      connections between them; and a homeostatic model, where connections are
      homeostatically regulated to maintain a constant level of excitatory activity
      based on spontaneous input. The homeostatic model successfully tunes network
      connectivity to generate robust activity patterns with appropriate timing
      relationships between neighboring populations. These timing relationships can be
      modulated by the properties of spontaneous activity, suggesting its instructive
      role for generating functional variability in network output. In contrast, the
      Hebbian model fails to produce the tight timing relationships between neighboring
      populations required for unidirectional activity propagation, even when
      additional assumptions are imposed to constrain synaptic growth. These results
      argue that homeostatic mechanisms are more likely than Hebbian mechanisms to tune
      weak connectivity based on spontaneous input in a recurrent network for rhythm
      generation and robust activity propagation. SIGNIFICANCE STATEMENT: How are
      neural circuits organized and tuned to maintain stable function and produce
      robust output? This task is especially difficult during development, when circuit
      properties change in response to variable environments and internal states. Many
      developing circuits exhibit spontaneous activity, but its role in the synaptic
      organization of motor networks that produce rhythmic output is unknown. We
      studied a model motor network, that when appropriately tuned, generates
      propagating activity as during crawling inDrosophilalarvae. Based on experimental
      evidence of activity-dependent tuning of connectivity, we examined plausible
      mechanisms by which appropriate connectivity emerges. Our results suggest that
      activity-dependent homeostatic mechanisms are better suited than Hebbian
      mechanisms for organizing motor network connectivity, and highlight an important
      difference from sensory areas.

PMID- 27030759
TI  - Passive Synaptic Normalization and Input Synchrony-Dependent Amplification of
      Cortical Feedback in Thalamocortical Neuron Dendrites.
AB  - Thalamocortical neurons have thousands of synaptic connections from layer VI
      corticothalamic neurons distributed across their dendritic trees. Although
      corticothalamic synapses provide significant excitatory input, it remains unknown
      how different spatial and temporal input patterns are integrated by
      thalamocortical neurons. Using dendritic recording, 2-photon glutamate uncaging,
      and computational modeling, we investigated how rat dorsal lateral geniculate
      nucleus thalamocortical neurons integrate excitatory corticothalamic feedback. We
      find that unitary corticothalamic inputs produce small somatic EPSPs whose
      amplitudes are passively normalized and virtually independent of the site of
      origin within the dendritic tree. Furthermore, uncaging of MNI glutamate reveals
      that thalamocortical neurons have postsynaptic voltage-dependent mechanisms that
      can amplify integrated corticothalamic input. These mechanisms, involving NMDA
      receptors and T-type Ca(2+)channels, require temporally synchronous synaptic
      activation but not spatially coincident input patterns. In hyperpolarized
      thalamocortical neurons, T-type Ca(2+)channels produce nonlinear amplification of
      temporally synchronous inputs, whereas asynchronous inputs are not amplified. At
      depolarized potentials, the input-output function for synchronous synaptic input
      is linear but shows enhanced gain due to activity-dependent recruitment of NMDA
      receptors. Computer simulations reveal that EPSP amplification by T-type
      Ca(2+)channels and NMDA receptors occurs when synaptic inputs are either
      clustered onto individual dendrites or when they are distributed throughout the
      dendritic tree. Consequently, postsynaptic EPSP amplification mechanisms limit
      the "modulatory" effects of corticothalamic synaptic inputs on thalamocortical
      neuron membrane potential and allow these synapses to act as synchrony-dependent
      "drivers" of thalamocortical neuron firing. These complex thalamocortical input
      output transformations significantly increase the influence of corticothalamic
      feedback on sensory information transfer. SIGNIFICANCE STATEMENT: Neurons in
      first-order thalamic nuclei transmit sensory information from the periphery to
      the cortex. However, the numerically dominant synaptic input to thalamocortical
      neurons comes from the cortex, which provides a strong, activity-dependent
      modulatory feedback influence on information flow through the thalamus. Here, we
      reveal how individual quantal-sized corticothalamic EPSPs propagate within
      thalamocortical neuron dendrites and how different spatial and temporal input
      patterns are integrated by these cells. We find that thalamocortical neurons have
      voltage- and synchrony-dependent postsynaptic mechanisms, involving NMDA
      receptors and T-type Ca(2+)channels that allow nonlinear amplification of
      integrated corticothalamic EPSPs. These mechanisms significantly increase the
      responsiveness of thalamocortical neurons to cortical excitatory input and
      broaden the "modulatory" influence exerted by corticothalamic synapses.

PMID- 27030761
TI  - Transient Pupil Dilation after Subsaccadic Microstimulation of Primate Frontal
      Eye Fields.
AB  - Pupillometry provides a simple and noninvasive index for a variety of cognitive
      processes, including perception, attention, task consolidation, learning, and
      memory. The neural substrates by which such cognitive processes influence pupil
      diameter remain somewhat unclear, although cortical inputs to the locus coeruleus
      mediating arousal are likely involved. Changes in pupil diameter also accompany
      covert orienting; hence the oculomotor system may provide an alternative
      substrate for cognitive influences on pupil diameter. Here, we show that low
      level electrical microstimulation of the primate frontal eye fields (FEFs), a
      cortical component of the oculomotor system strongly connected to the
      intermediate layers of the superior colliculus (SCi), evoked robust pupil
      dilation even in the absence of evoked saccades. The magnitude of such dilation
      scaled with increases in stimulation parameters, depending strongly on the
      intensity and number of pulses. Although there are multiple pathways by which FEF
      stimulation could cause pupil dilation, the timing and profile of dilation
      closely resembled that evoked by SCi stimulation. Moreover, pupil dilation evoked
      from the FEFs increased when presumed oculomotor activity was higher at the time
      of stimulation. Our findings implicate the oculomotor system as a potential
      substrate for how cognitive processes can influence pupil diameter. We suggest
      that a pathway from the frontal cortex through the SCi operates in parallel with
      frontal inputs to arousal circuits to regulate task-dependent modulation of pupil
      diameter, perhaps indicative of an organization wherein one pathway assumes
      primacy for a given cognitive process. SIGNIFICANCE STATEMENT: Pupillometry (the
      measurement of pupil diameter) provides a simple and noninvasive index for a
      variety of cognitive processes, offering a biomarker that has value in both
      health and disease. But how do cognitive processes influence pupil diameter?
      Here, we show that low-level stimulation of the primate frontal eye fields can
      induce robust pupil dilation without saccades. Pupil dilation scaled with the
      number and intensity of stimulation pulses and varied with endogenous oculomotor
      activity at the time of stimulation. The oculomotor system therefore provides a
      plausible pathway by which cognitive processes may influence pupil diameter,
      perhaps operating in conjunction with systems regulating arousal.

PMID- 27030760
TI  - Auditory Brainstem Response Latency in Noise as a Marker of Cochlear
      Synaptopathy.
AB  - Evidence from animal and human studies suggests that moderate acoustic exposure,
      causing only transient threshold elevation, can nonetheless cause "hidden hearing
      loss" that interferes with coding of suprathreshold sound. Such noise exposure
      destroys synaptic connections between cochlear hair cells and auditory nerve
      fibers; however, there is no clinical test of this synaptopathy in humans. In
      animals, synaptopathy reduces the amplitude of auditory brainstem response (ABR)
      wave-I. Unfortunately, ABR wave-I is difficult to measure in humans, limiting its
      clinical use. Here, using analogous measurements in humans and mice, we show that
      the effect of masking noise on the latency of the more robust ABR wave-V mirrors
      changes in ABR wave-I amplitude. Furthermore, in our human cohort, the effect of
      noise on wave-V latency predicts perceptual temporal sensitivity. Our results
      suggest that measures of the effects of noise on ABR wave-V latency can be used
      to diagnose cochlear synaptopathy in humans. SIGNIFICANCE STATEMENT: Although
      there are suspicions that cochlear synaptopathy affects humans with normal
      hearing thresholds, no one has yet reported a clinical measure that is a reliable
      marker of such loss. By combining human and animal data, we demonstrate that the
      latency of auditory brainstem response wave-V in noise reflects auditory nerve
      loss. This is the first study of human listeners with normal hearing thresholds
      that links individual differences observed in behavior and auditory brainstem
      response timing to cochlear synaptopathy. These results can guide development of
      a clinical test to reveal this previously unknown form of noise-induced hearing
      loss in humans.

PMID- 27030762
TI  - The Chemokine CCL2 Mediates the Seizure-enhancing Effects of Systemic
      Inflammation.
AB  - Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures.
      Brain inflammation is increasingly recognized as a critical factor for seizure
      precipitation, but the molecular mediators of such proconvulsant effects are only
      partly understood. The chemokine CCL2 is one of the most elevated inflammatory
      mediators in patients with pharmacoresistent epilepsy, but its contribution to
      seizure generation remains unexplored. Here, we show, for the first time, a
      crucial role for CCL2 and its receptor CCR2 in seizure control. We imposed a
      systemic inflammatory challenge via lipopolysaccharide (LPS) administration in
      mice with mesial temporal lobe epilepsy. We found that LPS dramatically increased
      seizure frequency and upregulated the expression of many inflammatory proteins,
      including CCL2. To test the proconvulsant role of CCL2, we administered
      systemically either a CCL2 transcription inhibitor (bindarit) or a selective
      antagonist of the CCR2 receptor (RS102895). We found that interference with CCL2
      signaling potently suppressed LPS-induced seizures. Intracerebral administration
      of anti-CCL2 antibodies also abrogated LPS-mediated seizure enhancement in
      chronically epileptic animals. Our results reveal that CCL2 is a key mediator in
      the molecular pathways that link peripheral inflammation with neuronal
      hyperexcitability. SIGNIFICANCE STATEMENT: Substantial evidence points to a role
      for inflammation in epilepsy, but currently there is little insight as to how
      inflammatory pathways impact on seizure generation. Here, we examine the
      molecular mediators linking peripheral inflammation with seizure susceptibility
      in mice with mesial temporal lobe epilepsy. We show that a systemic inflammatory
      challenge via lipopolysaccharide administration potently enhances seizure
      frequency and upregulates the expression of the chemokine CCL2. Remarkably,
      selective pharmacological interference with CCL2 or its receptor CCR2 suppresses
      lipopolysaccharide-induced seizure enhancement. Thus, CCL2/CCR2 signaling plays a
      key role in linking systemic inflammation with seizure susceptibility.

PMID- 27030763
TI  - Evidence for a Causal Contribution of Macaque Vestibular, But Not Intraparietal,
      Cortex to Heading Perception.
AB  - Multisensory convergence of visual and vestibular signals has been observed
      within a network of cortical areas involved in representing heading. Vestibular
      dominant heading tuning has been found in the macaque parietoinsular vestibular
      cortex (PIVC) and the adjacent visual posterior sylvian (VPS) area, whereas
      relatively balanced visual/vestibular tuning was encountered in the ventral
      intraparietal (VIP) area and visual-dominant tuning was found in the dorsal
      medial superior temporal (MSTd) area. Although the respective functional roles of
      these areas remain unclear, perceptual deficits in heading discrimination
      following reversible chemical inactivation of area MSTd area suggested that areas
      with vestibular-dominant heading tuning also contribute to behavior. To explore
      the roles of other areas in heading perception, muscimol injections were used to
      reversibly inactivate either the PIVC or the VIP area bilaterally in macaques.
      Inactivation of the anterior PIVC increased psychophysical thresholds when
      heading judgments were based on either optic flow or vestibular cues, although
      effects were stronger for vestibular stimuli. All behavioral deficits recovered
      within 36 h. Visual deficits were larger following inactivation of the posterior
      portion of the PIVC, likely because these injections encroached upon the VPS
      area, which contains neurons with optic flow tuning (unlike the PIVC). In
      contrast, VIP inactivation led to no behavioral deficits, despite the fact that
      VIP neurons show much stronger choice-related activity than MSTd neurons. These
      results suggest that the VIP area either provides a parallel and partially
      redundant pathway for this task, or does not participate in heading
      discrimination. In contrast, the PIVC/VPS area, along with the MSTd area, make
      causal contributions to heading perception based on either vestibular or visual
      signals. SIGNIFICANCE STATEMENT: Multisensory vestibular and visual signals are
      found in multiple cortical areas, but their causal contribution to self-motion
      perception has been previously tested only in the dorsal medial superior temporal
      (MSTd) area. In these experiments, we show that inactivation of the
      parietoinsular vestibular cortex (PIVC) also results in causal deficits during
      heading discrimination for both visual and vestibular cues. In contrast, ventral
      intraparietal (VIP) area inactivation led to no behavioral deficits, despite the
      fact that VIP neurons show much stronger choice-related activity than MSTd or
      PIVC neurons. These results demonstrate that choice-related activity does not
      always imply a causal role in sensory perception.

PMID- 27030764
TI  - Sleep Spindle Density Predicts the Effect of Prior Knowledge on Memory
      Consolidation.
AB  - Information that relates to a prior knowledge schema is remembered better and
      consolidates more rapidly than information that does not. Another factor that
      influences memory consolidation is sleep and growing evidence suggests that sleep
      related processing is important for integration with existing knowledge. Here, we
      perform an examination of how sleep-related mechanisms interact with schema
      dependent memory advantage. Participants first established a schema over 2 weeks.
      Next, they encoded new facts, which were either related to the schema or
      completely unrelated. After a 24 h retention interval, including a night of
      sleep, which we monitored with polysomnography, participants encoded a second set
      of facts. Finally, memory for all facts was tested in a functional magnetic
      resonance imaging scanner. Behaviorally, sleep spindle density predicted an
      increase of the schema benefit to memory across the retention interval. Higher
      spindle densities were associated with reduced decay of schema-related memories.
      Functionally, spindle density predicted increased disengagement of the
      hippocampus across 24 h for schema-related memories only. Together, these results
      suggest that sleep spindle activity is associated with the effect of prior
      knowledge on memory consolidation. SIGNIFICANCE STATEMENT: Episodic memories are
      gradually assimilated into long-term memory and this process is strongly
      influenced by sleep. The consolidation of new information is also influenced by
      its relationship to existing knowledge structures, or schemas, but the role of
      sleep in such schema-related consolidation is unknown. We show that sleep spindle
      density predicts the extent to which schemas influence the consolidation of
      related facts. This is the first evidence that sleep is associated with the
      interaction between prior knowledge and long-term memory formation.

PMID- 27030765
TI  - Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and
      Local Translation in the Growth Cone of Motor Neurons.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting
      spinal motor neurons. It is caused by reduced levels of the survival of motor
      neuron (SMN) protein, which plays an essential role in the biogenesis of
      spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the
      specific defects in the motor circuitry in SMA is still unclear, but SMN has also
      been implicated in mediating the axonal localization of mRNA-protein complexes,
      which may contribute to the axonal degeneration observed in SMA. Here, we report
      that SMN deficiency severely disrupts local protein synthesis within neuronal
      growth cones. We also identify the cytoskeleton-associated growth-associated
      protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from
      SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth
      cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1,
      restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth
      defects in SMA neurons. These findings demonstrate that SMN plays an important
      role in the localization and local translation of mRNAs with important axonal
      functions and suggest that disruption of this function may contribute to the
      axonal defects observed in SMA. SIGNIFICANCE STATEMENT: The motor neuron disease
      spinal muscular atrophy (SMA) is caused by reduced levels of the survival of
      motor neuron (SMN) protein, which plays a key role in assembling RNA/protein
      complexes that are essential for mRNA splicing. It remains unclear whether
      defects in this well characterized housekeeping function cause the specific
      degeneration of spinal motor neurons observed in SMA. Here, we describe an
      additional role of SMN in regulating the axonal localization and local
      translation of the mRNA encoding growth-associated protein 43 (GAP43). This study
      supports a model whereby SMN deficiency impedes transport and local translation
      of mRNAs important for neurite outgrowth and stabilization, thus contributing to
      axon degeneration, muscle denervation, and motor neuron cell death in SMA.

PMID- 27030766
TI  - Effective Connectivity from Early Visual Cortex to Posterior Occipitotemporal
      Face Areas Supports Face Selectivity and Predicts Developmental Prosopagnosia.
AB  - Face processing is mediated by interactions between functional areas in the
      occipital and temporal lobe, and the fusiform face area (FFA) and anterior
      temporal lobe play key roles in the recognition of facial identity. Individuals
      with developmental prosopagnosia (DP), a lifelong face recognition impairment,
      have been shown to have structural and functional neuronal alterations in these
      areas. The present study investigated how face selectivity is generated in
      participants with normal face processing, and how functional abnormalities
      associated with DP, arise as a function of network connectivity. Using functional
      magnetic resonance imaging and dynamic causal modeling, we examined effective
      connectivity in normal participants by assessing network models that include
      early visual cortex (EVC) and face-selective areas and then investigated the
      integrity of this connectivity in participants with DP. Results showed that a
      feedforward architecture from EVC to the occipital face area, EVC to FFA, and EVC
      to posterior superior temporal sulcus (pSTS) best explained how face selectivity
      arises in both controls and participants with DP. In this architecture, the DP
      group showed reduced connection strengths on feedforward connections carrying
      face information from EVC to FFA and EVC to pSTS. These altered network dynamics
      in DP contribute to the diminished face selectivity in the posterior
      occipitotemporal areas affected in DP. These findings suggest a novel view on the
      relevance of feedforward projection from EVC to posterior occipitotemporal face
      areas in generating cortical face selectivity and differences in face recognition
      ability. SIGNIFICANCE STATEMENT: Areas of the human brain showing enhanced
      activation to faces compared to other objects or places have been extensively
      studied. However, the factors leading to this face selectively have remained
      mostly unknown. We show that effective connectivity from early visual cortex to
      posterior occipitotemporal face areas gives rise to face selectivity.
      Furthermore, people with developmental prosopagnosia, a lifelong face recognition
      impairment, have reduced face selectivity in the posterior occipitotemporal face
      areas and left anterior temporal lobe. We show that this reduced face selectivity
      can be predicted by effective connectivity from early visual cortex to posterior
      occipitotemporal face areas. This study presents the first network-based account
      of how face selectivity arises in the human brain.

PMID- 27030768
TI  - Eliminating Direction Specificity in Visuomotor Learning.
AB  - The generalization of learning offers a unique window for investigating the
      nature of motor learning. Error-based motor learning reportedly cannot generalize
      to distant directions because the aftereffects are direction specific. This
      direction specificity is often regarded as evidence that motor adaptation is
      model-based learning, and is constrained by neuronal tuning characteristics in
      the primary motor cortices and the cerebellum. However, recent evidence indicates
      that motor adaptation also involves model-free learning and explicit strategy
      learning. Using rotation paradigms, here we demonstrate that savings (faster
      relearning), which is closely related to model-free learning and explicit
      strategy learning, is also direction specific. However, this new direction
      specificity can be abolished when the participants receive exposure to the
      generalization directions via an irrelevant visuomotor gain-learning task.
      Control evidence indicates that this exposure effect is weakened when direction
      error signals are absent during gain learning. Therefore, the direction
      specificity in visuomotor learning is not solely related to model-based learning;
      it may also result from the impeded expression of model-free learning and
      explicit strategy learning with untrained directions. Our findings provide new
      insights into the mechanisms underlying motor learning, and may have important
      implications for practical applications such as motor rehabilitation.
      SIGNIFICANCE STATEMENT: Motor learning is more useful if it generalizes to
      untrained scenarios when needed, especially for sports training and motor
      rehabilitation. However, as a form of motor learning, motor adaptation is
      typically direction specific. Here we first show that savings with motor
      adaptation, an index for model-free learning and explicit strategy learning in
      motor learning, is also direction specific. However, the participants' additional
      exposure to untrained directions via an irrelevant gain-learning task can enable
      the complete generalization of learning. Our findings challenge existing models
      of motor generalization and may have important implications for practical
      applications.

PMID- 27030767
TI  - Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as
      Revealed by High-Definition Transcranial Direct Current Stimulation.
AB  - A defining aspect of human cognition is the ability to integrate conceptual
      information into complex semantic combinations. For example, we can comprehend
      "plaid" and "jacket" as individual concepts, but we can also effortlessly combine
      these concepts to form the semantic representation of "plaid jacket." Many
      neuroanatomic models of semantic memory propose that heteromodal cortical hubs
      integrate distributed semantic features into coherent representations. However,
      little work has specifically examined these proposed integrative mechanisms and
      the causal role of these regions in semantic integration. Here, we test the
      hypothesis that the angular gyrus (AG) is critical for integrating semantic
      information by applying high-definition transcranial direct current stimulation
      (tDCS) to an fMRI-guided region-of-interest in the left AG. We found that anodal
      stimulation to the left AG modulated semantic integration but had no effect on a
      letter-string control task. Specifically, anodal stimulation to the left AG
      resulted in faster comprehension of semantically meaningful combinations like
      "tiny radish" relative to non-meaningful combinations, such as "fast blueberry,"
      when compared to the effects observed during sham stimulation and stimulation to
      a right-hemisphere control brain region. Moreover, the size of the effect from
      brain stimulation correlated with the degree of semantic coherence between the
      word pairs. These findings demonstrate that the left AG plays a causal role in
      the integration of lexical-semantic information, and that high-definition tDCS to
      an associative cortical hub can selectively modulate integrative processes in
      semantic memory. SIGNIFICANCE STATEMENT: A major goal of neuroscience is to
      understand the neural basis of behaviors that are fundamental to human
      intelligence. One essential behavior is the ability to integrate conceptual
      knowledge from semantic memory, allowing us to construct an almost unlimited
      number of complex concepts from a limited set of basic constituents (e.g., "leaf"
      and "wet" can be combined into the more complex representation "wet leaf"). Here,
      we present a novel approach to studying integrative processes in semantic memory
      by applying focal brain stimulation to a heteromodal cortical hub implicated in
      semantic processing. Our findings demonstrate a causal role of the left angular
      gyrus in lexical-semantic integration and provide motivation for novel
      therapeutic applications in patients with lexical-semantic deficits.

PMID- 27030769
TI  - ABCA7 Deficiency Accelerates Amyloid-beta Generation and Alzheimer's Neuronal
      Pathology.
AB  - In Alzheimer's disease (AD), the accumulation and deposition of amyloid-beta
      (Abeta) peptides in the brain is a central event. Abeta is cleaved from amyloid
      precursor protein (APP) by beta-secretase and gamma-secretase mainly in neurons.
      Although mutations inAPP,PS1, orPS2cause early-onset familial AD,ABCA7encoding
      ATP-binding cassette transporter A7 is one of the susceptibility genes for late
      onset AD (LOAD), in which itsloss-of-functionvariants increase the disease risk.
      ABCA7 is homologous to a major lipid transporter ABCA1 and is highly expressed in
      neurons and microglia in the brain. Here, we show that ABCA7 deficiency altered
      brain lipid profile and impaired memory in ABCA7 knock-out (Abca7(-/-)) mice.
      When bred to amyloid model APP/PS1 mice, plaque burden was exacerbated by ABCA7
      deficit.In vivomicrodialysis studies indicated that the clearance rate of Abeta
      was unaltered. Interestingly, ABCA7 deletion facilitated the processing of APP to
      Abeta by increasing the levels of beta-site APP cleaving enzyme 1 (BACE1) and
      sterol regulatory element-binding protein 2 (SREBP2) in primary neurons and mouse
      brains. Knock-down of ABCA7 expression in neurons caused endoplasmic reticulum
      stress highlighted by increased level of protein kinase R-like endoplasmic
      reticulum kinase (PERK) and increased phosphorylation of eukaryotic initiation
      factor 2alpha (eIF2alpha). In the brains of APP/PS1;Abca7(-/-)mice, the level of
      phosphorylated extracellular regulated kinase (ERK) was also significantly
      elevated. Together, our results reveal novel pathways underlying the association
      of ABCA7 dysfunction and LOAD pathogenesis. SIGNIFICANCE STATEMENT: Gene variants
      inABCA7encoding ATP-binding cassette transporter A7 are associated with the
      increased risk for late-onset Alzheimer's disease (AD). Importantly, we found the
      altered brain lipid profile and impaired memory in ABCA7 knock-out mice. The
      accumulation of amyloid-beta (Abeta) peptides cleaved from amyloid precursor
      protein (APP) in the brain is a key event in AD pathogenesis and we also found
      that ABCA7 deficit exacerbated brain Abeta deposition in amyloid AD model APP/PS1
      mice. Mechanistically, we found that ABCA7 deletion facilitated the processing of
      APP and Abeta production by increasing the levels of beta-secretase 1 (BACE1) in
      primary neurons and mouse brains without affecting the Abeta clearance rate in
      APP/PS1 mice. Our study demonstrates a novel mechanism underlying how
      dysfunctions of ABCA7 contribute to the risk for AD.

PMID- 27030770
TI  - The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for
      Development of Circadian Pacemaker Neuron Processes That Support Rhythmic
      Activity in Constant Darkness But Not during Light/Dark Cycles.
AB  - InDrosophila, a transcriptional feedback loop that is activated by CLOCK-CYCLE
      (CLK-CYC) complexes and repressed by PERIOD-TIMELESS (PER-TIM) complexes keeps
      circadian time. The timing of CLK-CYC activation and PER-TIM repression is
      regulated post-translationally, in part through rhythmic phosphorylation of CLK,
      PER, and TIM. Although kinases that control PER, TIM, and CLK levels, activity,
      and/or subcellular localization have been identified, less is known about
      phosphatases that control clock protein dephosphorylation. To identify clock
      relevant phosphatases, clock-cell-specific RNAi knockdowns
      ofDrosophilaphosphatases were screened for altered activity rhythms. One
      phosphatase that was identified, the receptor protein tyrosine phosphatase
      leukocyte-antigen-related (LAR), abolished activity rhythms in constant darkness
      (DD) without disrupting the timekeeping mechanism in brain pacemaker neurons.
      However, expression of the neuropeptide pigment-dispersing factor (PDF), which
      mediates pacemaker neuron synchrony and output, is eliminated in the dorsal
      projections from small ventral lateral (sLNv) pacemaker neurons whenLarexpression
      is knocked down during development, but not in adults. Loss ofLarfunction
      eliminates sLNvdorsal projections, but PDF expression persists in sLNvand large
      ventral lateral neuron cell bodies and their remaining projections. In contrast
      to the defects in lights-on and lights-off anticipatory activity seen in flies
      that lack PDF,LarRNAi knockdown flies anticipate the lights-on and lights-off
      transition normally. Our results demonstrate thatLaris required for sLNvdorsal
      projection development and suggest that PDF expression in LNvcell bodies and
      their remaining projections mediate anticipation of the lights-on and lights-off
      transitions during a light/dark cycle. SIGNIFICANCE STATEMENT: In animals,
      circadian clocks drive daily rhythms in physiology, metabolism, and behavior via
      transcriptional feedback loops. Because key circadian transcriptional activators
      and repressors are regulated by phosphorylation, we screened for phosphatases
      that alter activity rhythms when their expression was reduced. One such
      phosphatase, leukocyte-antigen-related (LAR), abolishes activity rhythms, but
      does not disrupt feedback loop function. Rather,Lardisrupts clock output by
      eliminating axonal processes from clock neurons that release pigment-dispersing
      factor (PDF) neuropeptide into the dorsal brain, but PDF expression persists in
      their cell bodies and remaining projections. In contrast to flies that lack PDF,
      flies that lackLaranticipate lights-on and lights-off transitions normally, which
      suggests that the remaining PDF expression mediates activity during light/dark
      cycles.

PMID- 27030772
TI  - Sticking to the story: outstanding challenges in gecko-inspired adhesives.
AB  - The natural clinging ability of geckos has inspired hundreds of studies seeking
      design principles that could be applied to creating synthetic adhesives with the
      same performance capabilities as the gecko: adhesives that use no glue, are self
      cleaning and reusable, and are insensitive to a wide range of surface chemistries
      and roughness. Important progress has been made, and the basic mechanics of how
      'hairy' adhesives work have been faithfully reproduced, advancing theory in
      surface science and portending diverse practical applications. However, after 15
      years, no synthetic mimic can yet perform as well as a gecko and simultaneously
      meet of all the criteria listed above. Moreover, processes for the production of
      inexpensive and scalable products are still not clearly in view. Here, we discuss
      our perspective on some of the gaps in understanding that still remain; these
      gaps in our knowledge should stimulate us to turn to deeper study of the way in
      which free-ranging geckos stick to the variety of surfaces found in their natural
      environments and to a more complete analysis of the materials composing the gecko
      toe pads.

PMID- 27030773
TI  - Flapping wing aerodynamics: from insects to vertebrates.
AB  - More than a million insects and approximately 11,000 vertebrates utilize flapping
      wings to fly. However, flapping flight has only been studied in a few of these
      species, so many challenges remain in understanding this form of locomotion. Five
      key aerodynamic mechanisms have been identified for insect flight. Among these is
      the leading edge vortex, which is a convergent solution to avoid stall for
      insects, bats and birds. The roles of the other mechanisms - added mass, clap and
      fling, rotational circulation and wing-wake interactions - have not yet been
      thoroughly studied in the context of vertebrate flight. Further challenges to
      understanding bat and bird flight are posed by the complex, dynamic wing
      morphologies of these species and the more turbulent airflow generated by their
      wings compared with that observed during insect flight. Nevertheless, three
      dimensionless numbers that combine key flow, morphological and kinematic
      parameters - the Reynolds number, Rossby number and advance ratio - govern
      flapping wing aerodynamics for both insects and vertebrates. These numbers can
      thus be used to organize an integrative framework for studying and comparing
      animal flapping flight. Here, we provide a roadmap for developing such a
      framework, highlighting the aerodynamic mechanisms that remain to be quantified
      and compared across species. Ultimately, incorporating complex flight maneuvers,
      environmental effects and developmental stages into this framework will also be
      essential to advancing our understanding of the biomechanics, movement ecology
      and evolution of animal flight. 

PMID- 27030771
TI  - Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine
      Cells and Drive the Refinement and Maintenance of Visual Circuits.
AB  - Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal
      patterns are critical for early activity-dependent circuit elaboration and
      refinement in the mammalian visual system. Three separate developmental wave
      epochs or stages have been described, but the mechanism(s) of pattern generation
      of each and their distinct roles in visual circuit development remain
      incompletely understood. We used neuroanatomical,in vitroandin
      vivoelectrophysiological, and optical imaging techniques in genetically
      manipulated mice to examine the mechanisms of wave initiation and propagation and
      the role of wave patterns in visual circuit development. Through deletion of
      beta2 subunits of nicotinic acetylcholine receptors (beta2-nAChRs) selectively
      from starburst amacrine cells (SACs), we show that mutual excitation among SACs
      is critical for Stage II (cholinergic) retinal wave propagation, supporting
      models of wave initiation and pattern generation from within a single retinal
      cell type. We also demonstrate that beta2-nAChRs in SACs, and normal wave
      patterns, are necessary for eye-specific segregation. Finally, we show that Stage
      III (glutamatergic) retinal waves are not themselves necessary for normal eye
      specific segregation, but elimination of both Stage II and Stage III retinal
      waves dramatically disrupts eye-specific segregation. This suggests that
      persistent Stage II retinal waves can adequately compensate for Stage III retinal
      wave loss during the development and refinement of eye-specific segregation.
      These experiments confirm key features of the "recurrent network" model for
      retinal wave propagation and clarify the roles of Stage II and Stage III retinal
      wave patterns in visual circuit development. SIGNIFICANCE STATEMENT: Spontaneous
      activity drives early mammalian circuit development, but the initiation and
      patterning of activity vary across development and among modalities. Cholinergic
      "retinal waves" are initiated in starburst amacrine cells and propagate to
      retinal ganglion cells and higher-order visual areas, but the mechanism
      responsible for creating their unique and critical activity pattern is
      incompletely understood. We demonstrate that cholinergic wave patterns are
      dictated by recurrent connectivity within starburst amacrine cells, and retinal
      ganglion cells act as "readouts" of patterned activity. We also show that eye
      specific segregation occurs normally without glutamatergic waves, but elimination
      of both cholinergic and glutamatergic waves completely disrupts visual circuit
      development. These results suggest that each retinal wave pattern during
      development is optimized for concurrently refining multiple visual circuits.

PMID- 27030774
TI  - Mechanical responses of rat vibrissae to airflow.
AB  - The survival of many animals depends in part on their ability to sense the flow
      of the surrounding fluid medium. To date, however, little is known about how
      terrestrial mammals sense airflow direction or speed. The present work analyzes
      the mechanical response of isolated rat macrovibrissae (whiskers) to airflow to
      assess their viability as flow sensors. Results show that the whisker bends
      primarily in the direction of airflow and vibrates around a new average position
      at frequencies related to its resonant modes. The bending direction is not
      affected by airflow speed or by geometric properties of the whisker. In contrast,
      the bending magnitude increases strongly with airflow speed and with the ratio of
      the whisker's arc length to base diameter. To a much smaller degree, the bending
      magnitude also varies with the orientation of the whisker's intrinsic curvature
      relative to the direction of airflow. These results are used to predict the
      mechanical responses of vibrissae to airflow across the entire array, and to show
      that the rat could actively adjust the airflow data that the vibrissae acquire by
      changing the orientation of its whiskers. We suggest that, like the whiskers of
      pinnipeds, the macrovibrissae of terrestrial mammals are multimodal sensors -
      able to sense both airflow and touch - and that they may play a particularly
      important role in anemotaxis. 

PMID- 27030775
TI  - Starvation stress during larval development facilitates an adaptive response in
      adult worker honey bees (Apis mellifera L.).
AB  - Most organisms are constantly faced with environmental changes and stressors. In
      diverse organisms, there is an anticipatory mechanism during development that can
      program adult phenotypes. The adult phenotype would be adapted to the predicted
      environment that occurred during organism maturation. However, whether this
      anticipatory mechanism is present in eusocial species is questionable because
      eusocial organisms are largely shielded from exogenous conditions by their stable
      nest environment. In this study, we tested whether food deprivation during
      development of the honey bee (Apis mellifera), a eusocial insect model, can shift
      adult phenotypes to better cope with nutritional stress. After subjecting fifth
      instar worker larvae to short-term starvation, we measured nutrition-related
      morphology, starvation resistance, physiology, endocrinology and behavior in the
      adults. We found that the larval starvation caused adult honey bees to become
      more resilient toward starvation. Moreover, the adult bees were characterized by
      reduced ovary size, elevated glycogen stores and juvenile hormone (JH) titers,
      and decreased sugar sensitivity. These changes, in general, can help adult
      insects survive and reproduce in food-poor environments. Overall, we found for
      the first time support for an anticipatory mechanism in a eusocial species, the
      honey bee. Our results suggest that this mechanism may play a role in honey bee
      queen-worker differentiation and worker division of labor, both of which are
      related to the responses to nutritional stress. 

PMID- 27030776
TI  - Larval starvation improves metabolic response to adult starvation in honey bees
      (Apis mellifera L.).
AB  - Environmental changes during development have long-term effects on adult
      phenotypes in diverse organisms. Some of the effects play important roles in
      helping organisms adapt to different environments, such as insect polymorphism.
      Others, especially those resulting from an adverse developmental environment,
      have a negative effect on adult health and fitness. However, recent studies have
      shown that those phenotypes influenced by early environmental adversity have
      adaptive value under certain (anticipatory) conditions that are similar to the
      developmental environment, though evidence is mostly from morphological and
      behavioral observations and it is still rare at physiological and molecular
      levels. In the companion study, we applied a short-term starvation treatment to
      fifth instar honey bee larvae and measured changes in adult morphology,
      starvation resistance, hormonal and metabolic physiology and gene expression. Our
      results suggest that honey bees can adaptively respond to the predicted
      nutritional stress. In the present study, we further hypothesized that
      developmental starvation specifically improves the metabolic response of adult
      bees to starvation instead of globally affecting metabolism under well-fed
      conditions. Here, we produced adult honey bees that had experienced a short-term
      larval starvation, then we starved them for 12 h and monitored metabolic rate,
      blood sugar concentrations and metabolic reserves. We found that the bees that
      experienced larval starvation were able to shift to other fuels faster and better
      maintain stable blood sugar levels during starvation. However, developmental
      nutritional stress did not change metabolic rates or blood sugar levels in adult
      bees under normal conditions. Overall, our study provides further evidence that
      early larval starvation specifically improves the metabolic responses to adult
      starvation in honey bees. 

PMID- 27030777
TI  - Phenotypic differences between the sexes in the sexually plastic mangrove rivulus
      fish (Kryptolebias marmoratus).
AB  - To maximize reproductive success, many animal species have evolved functional sex
      change. Theory predicts that transitions between sexes should occur when the
      fitness payoff of the current sex is exceeded by the fitness payoff of the
      opposite sex. We examined phenotypic differences between the sexes in a sex
      changing vertebrate, the mangrove rivulus fish (Kryptolebias marmoratus), to
      elucidate potential factors that might drive the 'decision' to switch sex.
      Rivulus populations consist of self-fertilizing hermaphrodites and males.
      Hermaphrodites transition into males under certain environmental conditions,
      affording us the opportunity to generate 40 hermaphrodite-male pairs where,
      within a pair, individuals possessed identical genotypes despite being different
      sexes. We quantified steroid hormone levels, behavior (aggression and risk
      taking), metabolism and morphology (organ masses). We found that hermaphrodites
      were more aggressive and risk averse, and had higher maximum metabolic rates and
      larger gonadosomatic indices. Males had higher steroid hormone levels and showed
      correlations among hormones that hermaphrodites lacked. Males also had greater
      total mass and somatic body mass and possessed considerable fat stores. Our
      findings suggest that there are major differences between the sexes in energy
      allocation, with hermaphrodites exhibiting elevated maximum metabolic rates, and
      showing evidence of favoring investments in reproductive tissues over somatic
      growth. Our study serves as the foundation for future research investigating how
      environmental challenges affect both physiology and reproductive investment and,
      ultimately, how these changes dictate the transition between sexes. 

PMID- 27030778
TI  - Stuck in gear: age-related loss of variable gearing in skeletal muscle.
AB  - Skeletal muscles power a broad diversity of animal movements, despite only being
      able to produce high forces over a limited range of velocities. Pennate muscles
      use a range of gear ratios, the ratio of muscle shortening velocity to fiber
      shortening velocity, to partially circumvent these force-velocity constraints.
      Muscles operate with a high gear ratio at low forces; fibers rotate to greater
      angles of pennation, enhancing velocity but compromising force. At higher forces,
      muscles operate with a lower gear ratio; fibers rotate little so limiting muscle
      shortening velocity, but helping to preserve force. This ability to shift gears
      is thought to be due to the interplay of contractile force and connective tissue
      constraints. In order to test this hypothesis, gear ratios were determined in the
      medial gastrocnemius muscles of both healthy young rats, and old rats where the
      interaction between contractile and connective tissue properties was assumed to
      be disrupted. Muscle fiber and aponeurosis stiffness increased with age (P<0.05)
      from 19.1+/-5.0 kPa and 188.5+/-24.2 MPa, respectively, in young rats to 39.1+/
      4.2 kPa and 328.0+/-48.3 MPa in old rats, indicating a mechanical change in the
      interaction between contractile and connective tissues. Gear ratio decreased with
      increasing force in young (P<0.001) but not old (P=0.72) muscles, indicating that
      variable gearing is lost in old muscle. These findings support the hypothesis
      that variable gearing results from the interaction between contractile and
      connective tissues and suggest novel explanations for the decline in muscle
      performance with age. 

PMID- 27030779
TI  - Broadband noise exposure does not affect hearing sensitivity in big brown bats
      (Eptesicus fuscus).
AB  - In many vertebrates, exposure to intense sounds under certain stimulus conditions
      can induce temporary threshold shifts that reduce hearing sensitivity.
      Susceptibility to these hearing losses may reflect the relatively quiet
      environments in which most of these species have evolved. Echolocating big brown
      bats (Eptesicus fuscus) live in extremely intense acoustic environments in which
      they navigate and forage successfully, both alone and in company with other bats.
      We hypothesized that bats may have evolved a mechanism to minimize noise-induced
      hearing losses that otherwise could impair natural echolocation behaviors. The
      hearing sensitivity of seven big brown bats was measured in active echolocation
      and passive hearing tasks, before and after exposure to broadband noise spanning
      their audiometric range (10-100 kHz, 116 dB SPL re. 20 uPa rms, 1 h duration;
      sound exposure level 152 dB). Detection thresholds measured 20 min, 2 h or 24 h
      after exposure did not vary significantly from pre-exposure thresholds or from
      thresholds in control (sham exposure) conditions. These results suggest that big
      brown bats may be less susceptible to temporary threshold shifts than are other
      terrestrial mammals after exposure to similarly intense broadband sounds. These
      experiments provide fertile ground for future research on possible mechanisms
      employed by echolocating bats to minimize hearing losses while orienting
      effectively in noisy biological soundscapes.

PMID- 27030780
TI  - Detection of artificial water flows by the lateral line system of a benthic
      feeding cichlid fish.
AB  - The mechanosensory lateral line system of fishes detects water motions within a
      few body lengths of the source. Several types of artificial stimuli have been
      used to probe lateral line function in the laboratory, but few studies have
      investigated the role of flow sensing in benthic feeding teleosts. In this study,
      we used artificial flows emerging from a sandy substrate to assess the
      contribution of flow sensing to prey detection in the peacock cichlid, Aulonocara
      stuartgranti, which feeds on benthic invertebrates in Lake Malawi. Using a
      positive reinforcement protocol, we trained fish to respond to flows lacking the
      visual and chemical cues generated by tethered prey in prior studies with A.
      stuartgranti Fish successfully responded to artificial flows at all five rates
      presented (characterized using digital particle image velocimetry), and showed a
      range of flow-sensing behaviors, including an unconditioned bite response.
      Immediately after lateral line inactivation, fish rarely responded to flows and
      the loss of vital fluorescent staining of hair cells (with 4-di-2-ASP) verified
      lateral line inactivation. Within 2 days post-treatment, some aspects of flow
      sensing behavior returned and after 7 days, flow-sensing behavior and hair cell
      fluorescence both returned to pre-treatment levels, which is consistent with the
      reported timing of hair cell regeneration in other vertebrates. The presentation
      of ecologically relevant water flows to assess flow-sensing behaviors and the use
      of a positive reinforcement protocol are methods that present new opportunities
      to study the role of flow sensing in the feeding ecology of benthic feeding
      fishes.

PMID- 27030781
TI  - Smithornis broadbills produce loud wing song by aeroelastic flutter of medial
      primary wing feathers.
AB  - Broadbills in the genus Smithornis produce a loud brreeeeet during a distinctive
      flight display. It has been posited that this klaxon-like sound is generated non
      vocally with the outer wing feathers (P9, P10), but no scientific studies have
      previously addressed this hypothesis. Although most birds that make non-vocal
      communication sounds have feathers with a shape distinctively modified for sound
      production, Smithornis broadbills do not. We investigated whether this song is
      produced vocally or with the wings in rufous-sided broadbill (S. rufolateralis)
      and African broad bill (S. capensis). In support of the wing song hypothesis,
      synchronized high-speed video and sound recordings of displays demonstrated that
      sound pulses were produced during the downstroke, subtle gaps sometimes appeared
      between the outer primary feathers P6-P10, and wing tip speed reached 16 m s(-1)
      Tests of a spread wing in a wind tunnel demonstrated that at a specific
      orientation, P6 and P7 flutter and produce sound. Wind tunnel tests on individual
      feathers P5-P10 from a male of each species revealed that while all of these
      feathers can produce sound via aeroelastic flutter, P6 and P7 produce the loudest
      sounds, which are similar in frequency to the wing song, at airspeeds achievable
      by the wing tip during display flight. Consistent with the wind tunnel
      experiments, field manipulations of P6, P7 and P8 changed the timbre of the wing
      song, and reduced its tonality, demonstrating that P6 and P7 are together the
      sound source, and not P9 or P10. The resultant wing song appears to have
      functionally replaced vocal song.

PMID- 27030782
TI  - Radical scavenging reaction kinetics with multiwalled carbon nanotubes.
AB  - Progress in the development of carbon nanotubes (CNTs) has stimulated great
      interest among industries providing new applications. Meanwhile, toxicological
      evaluations on nanomaterials are advancing leading to a predictive exposure limit
      for CNTs, which implies the possibility of designing safer CNTs. To pursue safety
      by design, the redox potential in reactions with CNTs has been contemplated
      recently. However, the chemical reactivity of CNTs has not been explored
      kinetically, so that there is no scheme to express a redox reaction with CNTs,
      though it has been investigated and reported. In addition, the reactivity of CNTs
      is discussed with regard to impurities that consist of transition metals in CNTs,
      which obfuscates the contribution of CNTs to the reaction. The present work aimed
      at modeling CNT scavenging in aqueous solution using a kinetic approach and a
      simple first-order reaction scheme. The results show that CNTs follow the redox
      reaction assumption in a simple chemical system. As a result, the reaction with
      multiwalled CNTs is semi-quantitatively denoted as redox potential, which
      suggests that their biological reactions may also be evaluated using a redox
      potential scheme.

PMID- 27030783
TI  - Evaluation of Patient Needs and Patient Navigator Communication about Cervical
      Cancer Prevention in Appalachian Kentucky.
AB  - Few studies describe the way patient navigation processes may address disparities
      in treatment and follow-up care for medically underserved populations. Using a
      social ecological framework, we analyzed survey assessments of 519 patients
      completing a randomized navigation trial in Appalachia Kentucky to examine
      patient-reported barriers to follow-up cervical cancer care. We also analyzed in
      depth interview transcripts with four lay patient navigators in the trial to
      identify barriers to follow-up care and to learn what communication strategies
      navigators use to successfully (or unsuccessfully) help patients navigate around
      those barriers. Our analysis provides insight into how patient navigation may
      improve adherence to follow-up care through assisted uncertainty management. We
      also discuss opportunities for improving navigator training to address
      disparities in clinical outcomes.

PMID- 27030784
TI  - The influence of sensation-seeking and parental and peer influences in early
      adolescence on risk involvement through middle adolescence: A structural equation
      modeling analysis.
AB  - This study examined the relationships between youth and parental sensation
      seeking, peer influence, parental monitoring and youth risk involvement in
      adolescence using structural equation modeling. Beginning in grade-six,
      longitudinal data were collected from 543 students over three years. Youth
      sensation-seeking in grade six contributed to risk involvement in early
      adolescence (grades six and seven) indirectly through increased peer risk
      influence and decreased parental monitoring but did not have a direct
      contribution. It contributed directly and indirectly to risk involvement in
      middle adolescence (grades eight and nine). Parent sensation-seeking at baseline
      was positively associated with peer risk influence and negatively associated with
      parental monitoring; it had no direct effect on adolescent risk involvement.
      Parental monitoring buffers negative peer influence on adolescent risk
      involvement. Results highlight the need for intervention efforts to provide
      normative feedback about adolescent risky behaviors and to vary among families in
      which parents and/or youth have high sensation-seeking propensities.

PMID- 27030785
TI  - Some tests for detecting trends based on the modified Baumgartner-Weibeta
      Schindler statistics.
AB  - We propose a modified nonparametric Baumgartner-Weibeta-Schindler test and
      investigate its use in testing for trends among K binomial populations. Exact
      conditional and unconditional approaches to p-value calculation are explored in
      conjunction with the statistic in addition to a similar test statistic proposed
      by Neuhauser (2006), the unconditional approaches considered including the
      maximization approach (Basu, 1977), the confidence interval approach (Berger and
      Boos, 1994), and the E + M approach (Lloyd, 2008). The procedures are compared
      with regard to actual Type I error and power and examples are provided. The
      conditional approach and the E + M approach performed well, with the E + M
      approach having an actual level much closer to the nominal level. The E + M
      approach and the conditional approach are generally more powerful than the other
      p-value calculation approaches in the scenarios considered. The power difference
      between the conditional approach and the E + M approach is often small in the
      balance case. However, in the unbalanced case, the power comparison between those
      two approaches based on our proposed test statistic show that the E+ M approach
      has higher power than the conditional approach.

PMID- 27030787
TI  - Computing Critical Values of Exact Tests by Incorporating Monte Carlo Simulations
      Combined with Statistical Tables.
AB  - Various exact tests for statistical inference are available for powerful and
      accurate decision rules provided that corresponding critical values are tabulated
      or evaluated via Monte Carlo methods. This article introduces a novel hybrid
      method for computing p-values of exact tests by combining Monte Carlo simulations
      and statistical tables generated a priori. To use the data from Monte Carlo
      generations and tabulated critical values jointly, we employ kernel density
      estimation within Bayesian-type procedures. The p-values are linked to the
      posterior means of quantiles. In this framework, we present relevant information
      from the Monte Carlo experiments via likelihood-type functions, whereas tabulated
      critical values are used to reflect prior distributions. The local maximum
      likelihood technique is employed to compute functional forms of prior
      distributions from statistical tables. Empirical likelihood functions are
      proposed to replace parametric likelihood functions within the structure of the
      posterior mean calculations to provide a Bayesian-type procedure with a
      distribution-free set of assumptions. We derive the asymptotic properties of the
      proposed nonparametric posterior means of quantiles process. Using the
      theoretical propositions, we calculate the minimum number of needed Monte Carlo
      resamples for desired level of accuracy on the basis of distances between actual
      data characteristics (e.g. sample sizes) and characteristics of data used to
      present corresponding critical values in a table. The proposed approach makes
      practical applications of exact tests simple and rapid. Implementations of the
      proposed technique are easily carried out via the recently developed STATA and R
      statistical packages.

PMID- 27030786
TI  - Conformational Modeling of Continuum Structures in Robotics and Structural
      Biology: A Review.
AB  - Hyper-redundant (or snakelike) manipulators have many more degrees of freedom
      than are required to position and orient an object in space. They have been
      employed in a variety of applications ranging from search-and-rescue to minimally
      invasive surgical procedures, and recently they even have been proposed as
      solutions to problems in maintaining civil infrastructure and the repair of
      satellites. The kinematic and dynamic properties of snakelike robots are captured
      naturally using a continuum backbone curve equipped with a naturally evolving set
      of reference frames, stiffness properties, and mass density. When the snakelike
      robot has a continuum architecture, the backbone curve corresponds with the
      physical device itself. Interestingly, these same modeling ideas can be used to
      describe conformational shapes of DNA molecules and filamentous protein
      structures in solution and in cells. This paper reviews several classes of
      snakelike robots: (1) hyper-redundant manipulators guided by backbone curves; (2)
      flexible steerable needles; and (3) concentric tube continuum robots. It is then
      shown how the same mathematical modeling methods used in these robotics contexts
      can be used to model molecules such as DNA. All of these problems are treated in
      the context of a common mathematical framework based on the differential geometry
      of curves, continuum mechanics, and variational calculus. Both coordinate
      dependent Euler-Lagrange formulations and coordinate-free Euler-Poincare
      approaches are reviewed.

PMID- 27030788
TI  - Gene Expression Profiling of Gastric Cancer.
AB  - Gastric cancer is the second leading cause of cancer death worldwide, both in men
      and women. A genomewide gene expression analysis was carried out to identify
      differentially expressed genes in gastric adenocarcinoma tissues as compared to
      adjacent normal tissues. We used Agilent's whole human genome oligonucleotide
      microarray platform representing ~41,000 genes to carry out gene expression
      analysis. Two-color microarray analysis was employed to directly compare the
      expression of genes between tumor and normal tissues. Through this approach, we
      identified several previously known candidate genes along with a number of novel
      candidate genes in gastric cancer. Testican-1 (SPOCK1) was one of the novel
      molecules that was 10-fold upregulated in tumors. Using tissue microarrays, we
      validated the expression of testican-1 by immunohistochemical staining. It was
      overexpressed in 56% (160/282) of the cases tested. Pathway analysis led to the
      identification of several networks in which SPOCK1 was among the topmost networks
      of interacting genes. By gene enrichment analysis, we identified several genes
      involved in cell adhesion and cell proliferation to be significantly upregulated
      while those corresponding to metabolic pathways were significantly downregulated.
      The differentially expressed genes identified in this study are candidate
      biomarkers for gastric adenoacarcinoma.

PMID- 27030790
TI  - Economic Costs of a Postrelease Intervention for Incarcerated Female Substance
      Abusers: Recovery Management Checkups for Women Offenders (RMC-WO).
AB  - This study estimates the economic costs of Recovery Management Checkups for Women
      Offenders (RMC-WO), highlighting the unique mix of services and differential
      costs between two distinct phases of the intervention. Participants were randomly
      assigned to quarterly outcome monitoring (OM) only (n=242) or OM plus Recovery
      Management Checkups (OM-plus-RMC) (n=238). The OM-only condition has a total
      annual economic cost of $76,010, which equates to $81 quarterly per person. The
      average cost per OM interview completed is $86. OM-plus-RMC generates a total
      annual economic cost of $126,717, or $137 quarterly per person. The cost per
      interview completed is $147 and the cost per intervention session completed is
      $161. RMC-WO has a relatively modest additional cost compared with the average
      costs of post-release supervision, which can range from $3.42 ($1,250) per day
      (year) for probationers to $7.47 ($2,750) per day (year) for parolees. The
      clinical, economic, and policy implications of incorporating RMC-WO into existing
      corrections and/or community-based treatment settings are discussed.

PMID- 27030791
TI  - An Attentional Goldilocks Effect: An Optimal Amount of Social Interactivity
      Promotes Word Learning from Video.
AB  - Television can be a powerful education tool; however, content-makers must
      understand the factors that engage attention and promote learning from screen
      media. Prior research suggests that social engagement is critical for learning
      and that interactivity may enhance the educational quality of children's media.
      The present study examined the effects of increasing the social interactivity of
      television on children's visual attention and word learning. Three- to 5-year-old
      (MAge = 4;5 years, SD = 9 months) children completed a task in which they viewed
      videos of an actress teaching them the Swahili label for an on-screen image. Each
      child viewed these video clips in four conditions that parametrically manipulated
      social engagement and interactivity. We then tested whether each child had
      successfully learned the Swahili labels. Though 5-year-old children were able to
      learn words in all conditions, we found that there was an optimal level of social
      engagement that best supported learning for all participants, defined by engaging
      the child but not distracting from word labeling. Our eye-tracking data indicated
      that children in this condition spent more time looking at the target image and
      less time looking at the actress's face as compared to the most interactive
      condition. These findings suggest that social interactivity is critical to
      engaging attention and promoting learning from screen media up until a certain
      point, after which social stimuli may draw attention away from target images and
      impair children's word learning.

PMID- 27030789
TI  - The Power of Theory, Research Design, and Transdisciplinary Integration in Moving
      Psychopathology Forward.
AB  - While the past few decades have seen much work in psychopathology research that
      has yielded provocative insights, relatively little progress has been made in
      understanding the etiology of mental disorders. We contend that this is due to an
      overreliance on statistics and technology with insufficient attention to adequacy
      of experimental design, a lack of integration of data across various domains of
      research, and testing of theoretical models using relatively weak study designs.
      We provide a conceptual discussion of these issues and follow with a concrete
      demonstration of our proposed solution. Using two different disorders -
      depression and substance use - as examples, we illustrate how we can evaluate
      competing theories regarding their etiology by integrating information from
      various domains including latent variable models, neurobiology, and quasi
      experimental data such as twin and adoption studies, rather than relying on any
      single methodology alone. More broadly, we discuss the extent to which such
      integrative thinking allows for inferences about the etiology of mental
      disorders, rather than focusing on descriptive correlates alone. Greater
      scientific insight will require stringent tests of competing theories and a
      deeper conceptual understanding of the advantages and pitfalls of methodologies
      and criteria we use in our studies.

PMID- 27030792
TI  - Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl)
      valine peptides of beta-hemoglobin for better diagnostics in diabetes.
AB  - BACKGROUND: N-1-(Deoxyfructosyl) valine (DFV) beta-hemoglobin (beta-Hb), commonly
      referred as HbA1c, is widely used diagnostic marker in diabetes, believed to
      provide glycemic status of preceding 90-120 days. However, the turnover of
      hemoglobin is about 120 days, the DFV-beta-Hb, an early and reversible glycation
      product eventually may undergo irreversible advanced glycation modifications such
      as carboxymethylation or carboxyethylation. Hence quantification of N-1
      (carboxymethyl) valine (CMV) and N-1-(carboxyethyl) valine (CEV) peptides of beta
      Hb would be useful in assessing actual glycemic status. RESULTS: Fragment ion
      library for synthetically glycated peptides of hemoglobin was generated by using
      high resolution-accurate mass spectrometry (HR/AM). Using parallel reaction
      monitoring, deoxyfructosylated, carboxymethylated and carboxyethylated peptides
      of hemoglobin were quantified in clinical samples from healthy control, pre
      diabetes, diabetes and poorly controlled diabetes. For the first time, we report
      N-1-beta-valine undergoes carboxyethylation and mass spectrometric quantification
      of CMV and CEV peptides of beta-hemoglobin. Carboxymethylation was found to be
      the most abundant modification of N-1-beta-valine. Both CMV-beta-Hb and CEV-beta
      Hb peptides showed better correlation with severity of diabetes in terms of
      fasting glucose, postprandial glucose and microalbuminuria. CONCLUSIONS: This
      study reports carboxymethylation as a predominant modification of N-1-beta-valine
      of Hb, and quantification of CMV-beta-Hb and CEV-beta-Hb could be useful
      parameter for assessing the severity of diabetes.

PMID- 27030793
TI  - Schools as smoke-free zones? Barriers and facilitators to the adoption of outdoor
      school ground smoking bans at secondary schools.
AB  - BACKGROUND: Whereas smoking bans inside secondary school buildings are relatively
      widespread, a smoking ban for the outdoor school grounds is less common.
      Therefore, this study investigates why many secondary schools fail to adopt an
      outdoor school ground smoking ban. The aim is to elucidate the perceived barriers
      and facilitators of stakeholders at schools without an outdoor school ground
      smoking ban. METHODS: Qualitative data were obtained from 60 respondents of 15
      secondary schools. Semi-structured interviews were held with various key
      stakeholders and a thematic approach was used for analysis of the transcripts.
      RESULTS: The perceived barriers and facilitators of the stakeholders fell into
      four categories: 1) socio-political characteristics (legislation and social
      norm), 2) school characteristics (policy, decision process, enforcement,
      resources, workforce conditions, communication and collaboration), 3) individual
      characteristics (support, knowledge, and target group), and 4) smoking ban
      characteristics (environmental factors, guideline recommendations, outcome
      expectations, and evidence). CONCLUSIONS: These findings highlight the importance
      of legislation for outdoor smoking bans. Moreover, collaboration, communication
      and involving stakeholders during an early stage of the process should be
      stimulated, as this might increase adoption. These results can be applied in
      future studies on outdoor tobacco control policies; moreover, they may facilitate
      tobacco control initiatives leading to more smoke-free environments to further
      protect youth from the harmful effects of tobacco.

PMID- 27030795
TI  - C1D family proteins in coordinating RNA processing, chromosome condensation and
      DNA damage response.
AB  - Research on the involvement of C1D and its yeast homologues Rrp47 (S. cerevisiae)
      and Cti1 (S. pombe) in DNA damage repair and RNA processing has remained mutually
      exclusive, with most studies predominantly concentrating on Rrp47. This review
      will look to reconcile the functions of these proteins in their involvement with
      the RNA exosome, in the regulation of chromatin architecture, and in the repair
      of DNA double-strand breaks, focusing on non-homologous end joining and
      homologous recombination. We propose that C1D is situated in a central position
      to maintain genomic stability at highly transcribed gene loci by coordinating
      these processes through the timely recruitment of relevant regulatory factors. In
      the event that the damage is beyond repair, C1D induces apoptosis in a p53
      dependent manner. 

PMID- 27030796
TI  - Mitochondria-cytoskeleton associations in mammalian cytokinesis.
AB  - BACKGROUND: The role of the cytoskeleton in regulating mitochondrial distribution
      in dividing mammalian cells is poorly understood. We previously demonstrated that
      mitochondria are transported to the cleavage furrow during cytokinesis in a
      microtubule-dependent manner. However, the exact subset of spindle microtubules
      and molecular machinery involved remains unknown. METHODS: We employed
      quantitative imaging techniques and structured illumination microscopy to analyse
      the spatial and temporal relationship of mitochondria with microtubules and actin
      of the contractile ring during cytokinesis in HeLa cells. RESULTS:
      Superresolution microscopy revealed that mitochondria were associated with astral
      microtubules of the mitotic spindle in cytokinetic cells. Dominant-negative
      mutants of KIF5B, the heavy chain of kinesin-1 motor, and of Miro-1 disrupted
      mitochondrial transport to the furrow. Live imaging revealed that mitochondrial
      enrichment at the cell equator occurred simultaneously with the appearance of the
      contractile ring in cytokinesis. Inhibiting RhoA activity and contractile ring
      assembly with C3 transferase, caused mitochondrial mislocalisation during
      division. CONCLUSIONS: Taken together, the data suggest a model in which
      mitochondria are transported by a microtubule-mediated mechanism involving
      equatorial astral microtubules, Miro-1, and KIF5B to the nascent actomyosin
      contractile ring in cytokinesis.

PMID- 27030797
TI  - Analyzing the Chinese landscape in anti-diabetic drug research: leading knowledge
      production institutions and thematic communities.
AB  - BACKGROUND: The discovery of anti-diabetic drugs is an active Chinese medicine
      research area. This study aims to map out anti-diabetic drug research in China
      using a network-based systemic approach based on co-authorship of academic
      publications. We focused on identifying leading knowledge production
      institutions, analyzing interactions among them, detecting communities with high
      internal associations, and exploring future research directions. METHODS: Target
      articles published in 2009-2013 under the topic "diabetes" and subject category
      "pharmacology & pharmacy," with "China," "Taiwan," "Hong Kong," or "Macao" (or
      "Macau") in the authors' address field were retrieved from the science citation
      index expanded database and their bibliographic information (e.g., article title,
      authors, keywords, and authors' affiliation addresses) analyzed. A social network
      approach was used to construct an institutional collaboration network based on co
      publications. Gephi software was used to visualize the network and relationships
      among institutes were analyzed using centrality measurements. Thematic analysis
      based on article keywords and R sc value was applied to reveal the research
      hotspots and directions of network communities. RESULTS: The top 50 institutions
      were identified; these included Shanghai Jiao Tong University, National Taiwan
      University, Peking University, and China Pharmaceutical University. Institutes
      from Taiwan tended to cooperate with institutes outside Taiwan, but those from
      mainland China showed low interest in external collaboration. Fourteen thematic
      communities were detected with the Louvain algorithm and further labeled by their
      high-frequency and characteristic keywords, such as Chinese medicines, diabetic
      complications, oxidative stress, pharmacokinetics, and insulin resistance. The
      keyword Chinese medicines comprised a range of Chinese medicine-related topics,
      including berberine, flavonoids, Astragalus polysaccharide, emodin, and
      ginsenoside. These keywords suggest potential fields for further anti-diabetic
      drug research. The correlation of -0.641 (P = 0.013) between degree centrality
      and the R sc value of non-core keywords indicates that communities concentrating
      on rare research fields are usually isolated by others and have a lower chance of
      collaboration. CONCLUSION: With a better understanding of the Chinese landscape
      in anti-diabetic drug research, researchers and scholars looking for experts and
      institutions in a specific research area can rapidly spot their target community,
      then select the most appropriate potential collaborator and suggest preferential
      research directions for future studies.

PMID- 27030798
TI  - HPV genotype distribution and anomalous association of HPV33 to cervical
      neoplastic lesions in San Luis Potosi, Mexico.
AB  - BACKGROUND: The association of human papillomavirus (HPV) types to neoplastic
      lesions increase as a function of their oncogenicity and the duration of the
      infection since lesion severity progresses from low-grade to high-grade and
      cancer. In an outbreak, the prevalence of the HPV type involved would increase
      and the proportion of the associated low-grade lesions would predominate over
      severe lesions. In this study, the prevalence of HPV types and their association
      to neoplastic lesions was determined in women subjected to colposcopy in San Luis
      Potosi, Mexico. METHODS: DNA from high-risk (HR) and low-risk (LR) HPV types was
      identified by E6 nested multiplex PCR in cervical scrapes from 700 women with
      normal cytology, atypical squamous cells of undetermined significance (ASCUS),
      low-grade squamous intraepithelial lesions (LSIL), high-grade squamous
      intraepithelial lesions (HSIL) or invasive cervical cancer (CC). RESULTS: Overall
      HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was
      21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas
      that of single infections was 52 % and that of multiple infections (i.e., by 2-6
      HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6
      %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal
      cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC.
      Three prevalence trends for HR-HPV types were found in neoplastic lesions of
      increasing severity: increasing (LSIL < HSIL < CC) for HPV16, HPV39, HPV18,
      HPV58, HPV31 and HPV35; asymptotic (LSIL < HSIL ~ CC) for HPV51 and HPV68; U
      shaped (LSIL < HSIL > CC) for HPV33. CONCLUSIONS: Two-thirds of the women
      subjected to colposcopy from 2007 to 2010 in San Luis Potosi have HPV infections
      which predominate in the 15-24 years group. Around half of the infections are by
      one viral type and the rest by 2-6 types. HPV33 is the most prevalent type,
      followed by HPV16. Overall HR-HPV prevalence increases with the severity of
      neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend
      with progressing neoplastic lesions differs from the growing/asymptotic trends of
      other HR-HPV types. An ongoing or recent HPV33 outbreak is consistent with its
      high prevalence and anomalous association to LSIL.

PMID- 27030799
TI  - Transgender men and pregnancy.
AB  - Transgender people have experienced significant advances in societal acceptance
      despite experiencing continued stigma and discrimination. While it can still be
      difficult to access quality health care, and there is a great deal to be done to
      create affirming health care organizations, there is growing interest around the
      United States in advancing transgender health. The focus of this commentary is to
      provide guidance to clinicians caring for transgender men or other gender
      nonconforming people who are contemplating, carrying, or have completed a
      pregnancy. Terms transgender and gender nonconforming specifically refer to those
      whose gender identity (e.g., being a man) differs from their female sex assigned
      at birth. Many, if not most transgender men retain their female reproductive
      organs and retain the capacity to have children. Review of their experience
      demonstrates the need for preconception counseling that includes discussion of
      stopping testosterone while trying to conceive and during pregnancy, and
      anticipating increasing experiences of gender dysphoria during and after
      pregnancy. The clinical aspects of delivery itself fall within the realm of
      routine obstetrical care, although further research is needed into how mode and
      environment of delivery may affect gender dysphoria. Postpartum considerations
      include discussion of options for chest (breast) feeding, and how and when to
      reinitiate testosterone. A positive perinatal experience begins from the moment
      transgender men first present for care and depends on comprehensive affirmation
      of gender diversity.

PMID- 27030794
TI  - The role of cullin 5-containing ubiquitin ligases.
AB  - The suppressor of cytokine signaling (SOCS) box consists of the BC box and the
      cullin 5 (Cul5) box, which interact with Elongin BC and Cul5, respectively. SOCS
      box-containing proteins have ubiquitin ligase activity mediated by the formation
      of a complex with the scaffold protein Cul5 and the RING domain protein Rbx2, and
      are thereby members of the cullin RING ligase superfamily. Cul5-type ubiquitin
      ligases have a variety of substrates that are targeted for polyubiquitination and
      proteasomal degradation. Here, we review the current knowledge on the
      identification of Cul5 and the regulation of its expression, as well as the
      signaling pathways regulated by Cul5 and how viruses highjack the Cul5 system to
      overcome antiviral responses. 

PMID- 27030800
TI  - A complete annotation of the chromosomes of the cellulase producer Trichoderma
      reesei provides insights in gene clusters, their expression and reveals genes
      required for fitness.
AB  - BACKGROUND: Investigations on a few eukaryotic model organisms showed that many
      genes are non-randomly distributed on chromosomes. In addition, chromosome ends
      frequently possess genes that are important for the fitness of the organisms.
      Trichoderma reesei is an industrial producer of enzymes for food, feed and
      biorefinery production. Its seven chromosomes have recently been assembled, thus
      making an investigation of its chromosome architecture possible. RESULTS: We
      manually annotated and mapped 9194 ORFs on their respective chromosomes and
      investigated the clustering of the major gene categories and of genes encoding
      carbohydrate-active enzymes (CAZymes), and the relationship between clustering
      and expression. Genes responsible for RNA processing and modification, amino acid
      metabolism, transcription, translation and ribosomal structure and biogenesis
      indeed showed loose clustering, but this had no impact on their expression. A
      third of the genes encoding CAZymes also occurred in loose clusters that also
      contained a high number of genes encoding small secreted cysteine-rich proteins.
      Five CAZyme clusters were located less than 50 kb apart from the chromosome ends.
      These genes exhibited the lowest basal (but not induced) expression level, which
      correlated with an enrichment of H3K9 methylation in the terminal 50 kb areas
      indicating gene silencing. No differences were found in the expression of CAZyme
      genes present in other parts of the chromosomes. The putative subtelomeric areas
      were also enriched in genes encoding secreted proteases, amino acid permeases,
      enzyme clusters for polyketide synthases (PKS)-non-ribosomal peptide synthase
      (NRPS) fusion proteins (PKS-NRPS) and proteins involved in iron scavenging. They
      were strongly upregulated during conidiation and interaction with other fungi.
      CONCLUSIONS: Our findings suggest that gene clustering on the T. reesei
      chromosomes occurs but generally has no impact on their expression. CAZyme genes,
      located in subtelomers, however, exhibited a much lower basal expression level.
      The gene inventory of the subtelomers suggests a major role of competition for
      nitrogen and iron supported by antibiosis for the fitness of T. reesei. The
      availability of fully annotated chromosomes will facilitate the use of genetic
      crossings in identifying still unknown genes responsible for specific traits of
      T. reesei.

PMID- 27030801
TI  - The high mobility group protein HMO1 functions as a linker histone in yeast.
AB  - BACKGROUND: Eukaryotic chromatin consists of nucleosome core particles connected
      by linker DNA of variable length. Histone H1 associates with the linker DNA to
      stabilize the higher-order chromatin structure and to modulate the ability of
      regulatory factors to access their nucleosomal targets. In Saccharomyces
      cerevisiae, the protein with greatest sequence similarity to H1 is Hho1p.
      However, during vegetative growth, hho1? cells do not show any discernible cell
      growth defects or the changes in bulk chromatin structure that are characteristic
      of chromatin from multicellular eukaryotes in which H1 is depleted. In contrast,
      the yeast high mobility group (HMGB) protein HMO1 has been reported to compact
      chromatin, as evidenced by increased nuclease sensitivity in hmo1? cells. HMO1
      has an unusual domain architecture compared to vertebrate HMGB proteins in that
      the HMG domains are followed by a lysine-rich extension instead of an acidic
      domain. We address here the hypothesis that HMO1 serves the role of H1 in terms
      of chromatin compaction and that this function requires the lysine-rich
      extension. RESULTS: We show here that HMO1 fulfills this function of a linker
      histone. For histone H1, chromatin compaction requires its basic C-terminal
      domain, and we find that the same pertains to HMO1, as deletion of its C-terminal
      lysine-rich extension renders chromatin nuclease sensitive. On rDNA, deletion of
      both HMO1 and Hho1p is required for significantly increased nuclease sensitivity.
      Expression of human histone H1 completely reverses the nuclease sensitivity
      characteristic of chromatin isolated from hmo1? cells. While chromatin remodeling
      events associated with repair of DNA double-strand breaks occur faster in the
      more dynamic chromatin environment created by the hmo1 deletion, expression of
      human histone H1 results in chromatin remodeling and double-strand break repair
      similar to that observed in wild-type cells. CONCLUSION: Our data suggest that S.
      cerevisiae HMO1 protects linker DNA from nuclease digestion, a property also
      characteristic of mammalian linker histone H1. Notably, association with HMO1
      creates a less dynamic chromatin environment that depends on its lysine-rich
      domain. That HMO1 has linker histone function has implications for investigations
      of chromatin structure and function as well as for evolution of proteins with
      roles in chromatin compaction.

PMID- 27030802
TI  - Impact of similarity threshold on the topology of molecular similarity networks
      and clustering outcomes.
AB  - BACKGROUND: Complex network theory based methods and the emergence of "Big Data"
      have reshaped the terrain of investigating structure-activity relationships of
      molecules. This change gave rise to new methods which need to face an important
      challenge, namely: how to restructure a large molecular dataset into a network
      that best serves the purpose of the subsequent analyses. With special focus on
      network clustering, our study addresses this open question by proposing a data
      transformation method and a clustering framework. RESULTS: Using the WOMBAT and
      PubChem MLSMR datasets we investigated the relation between varying the
      similarity threshold applied on the similarity matrix and the average clustering
      coefficient of the emerging similarity-based networks. These similarity networks
      were then clustered with the InfoMap algorithm. We devised a systematic method to
      generate so-called "pseudo-reference" clustering datasets which compensate for
      the lack of large-scale reference datasets. With help from the clustering
      framework we were able to observe the effects of varying the similarity threshold
      and its consequence on the average clustering coefficient and the clustering
      performance. CONCLUSIONS: We observed that the average clustering coefficient
      versus similarity threshold function can be characterized by the presence of a
      peak that covers a range of similarity threshold values. This peak is preceded by
      a steep decline in the number of edges of the similarity network. The maximum of
      this peak is well aligned with the best clustering outcome. Thus, if no reference
      set is available, choosing the similarity threshold associated with this peak
      would be a near-ideal setting for the subsequent network cluster analysis. The
      proposed method can be used as a general approach to determine the appropriate
      similarity threshold to generate the similarity network of large-scale molecular
      datasets.

PMID- 27030803
TI  - Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular
      Neural Networks.
AB  - Ms. Pac-Man is a challenging video game in which multiple modes of behavior are
      required: Ms. Pac-Man must escape ghosts when they are threats and catch them
      when they are edible, in addition to eating all pills in each level. Past
      approaches to learning behavior in Ms. Pac-Man have treated the game as a single
      task to be learned using monolithic policy representations. In contrast, this
      paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve
      modular neural networks. Each module defines a separate behavior. The modules are
      used at different times according to a policy that can be human-designed (i.e.
      Multitask) or discovered automatically by evolution. The appropriate number of
      modules can be fixed or discovered using a genetic operator called Module
      Mutation. Several versions of Module Mutation are evaluated in this paper. Both
      fixed modular networks and Module Mutation networks outperform monolithic
      networks and Multitask networks. Interestingly, the best networks dedicate
      modules to critical behaviors (such as escaping when surrounded after luring
      ghosts near a power pill) that do not follow the customary division of the game
      into chasing edible and escaping threat ghosts. The results demonstrate that MM
      NEAT can discover interesting and effective behavior for agents in challenging
      games.

PMID- 27030804
TI  - Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First
      Degree Relatives".
AB  - We comment on the recent report entitled "Platelet Studies in Autism Spectrum
      Disorder Patients and First-Degree Relatives" [Molecular Autism 2015;6:57]. We
      find it commendable that the authors have investigated platelet factors
      potentially involved in the well-replicated observation of platelet
      hyperserotonemia in autism. However, we believe the results need a fuller
      discussion in the context of prior studies, think that certain aspects of the
      interpretation need to be reassessed, and attempt to provide a framework for
      further research in this area. 

PMID- 27019692
TI  - Developing a wintering waterfowl community baseline for environmental monitoring
      of Narragansett Bay, Rhode Island.
AB  - In 2004, the Atlantic Ecology Division of the US Environmental Protection
      Agency's Office of Research and Development began an annual winter waterfowl
      survey of Rhode Island's Narragansett Bay. Herein, we explore the survey data
      gathered from 2004 to 2011 in order to establish a benchmark understanding of our
      waterfowl communities and to establish a statistical framework for future
      environmental monitoring. The abundance and diversity of wintering waterfowl were
      relatively stable during the initial years of this survey, except in 2010 when
      there was a large spike in abundance and a reciprocal fall in diversity. There
      was no significant change in ranked abundance of most waterfowl species, with
      only Bufflehead ( Bucephala albeola) and Hooded Merganser ( Lophodytes cucllatus)
      showing a slight yet significant upward trend during the course of our survey
      period. Nonmetric multidimensional scaling (NMDS) was used to examine the
      community structure of wintering waterfowl. The results of the NMDS indicate that
      there is a spatial structure to the waterfowl communities of Narragansett Bay and
      this structure has remained relatively stable since the survey began. Our NMDS
      analysis helps to solidify what is known anecdotally about the bay's waterfowl
      ecology, and provides a formalized benchmark for long-term monitoring of
      Narragansett Bay's waterfowl communities. Birds, including waterfowl, are
      preferred bioindicators and we propose using our multivariate approach to monitor
      the future health of the bay. While this research focuses on a specific area of
      New England, these methods can be easily applied to novel areas of concern and
      provide a straightforward nonparametric approach to community-level monitoring.
      The methods provide a statistic test to examine potential drivers of community
      turnover and well-suited visualization tools. 

PMID- 27030806
TI  - Quantitative evaluation of extended-spectrum beta-lactamase-producing Escherichia
      coli strains in the wastewater of a French teaching hospital and relation to
      patient strain.
AB  - BACKGROUND: Extended-spectrum beta-lactamase-producing Escherichia coli has
      become ubiquitous and has been reported in diverse ecosystems. We evaluated the
      potential impact of post-acute and long-term healthcare activities on the
      environment by quantifying ESBL-producing Enterobacteriaceae in wastewaters of a
      French geriatric hospital. METHODS: We collected wastewater specimens
      representative of one-day efflux immediately before the connection with the
      municipal sewer pipe. The sample was processed following two different methods:
      dilution-filtration method and concentration method and was screened for ESBL
      producing Enterobacteriaceae using selective media. ESBL E. coli strains were
      quantified, screened for ESBL genes and compared with ESBL strains isolated from
      patients present in the building at the time of wastewater collection, using
      molecular methods. RESULTS: Six distinct environmental ESBL E. coli clusters were
      identified, two of them related to patient strains. The concentrations in
      hospital wastewater of these strains ranged from 2.5 * 10(4) to 10(6) UFC/L.
      CONCLUSIONS: Our results demonstrate that the presence of ESBL E. coli patients
      leads to a dissemination of ESBL E. coli in the environment and highlights the
      need to improve excreta and wastewater policy in hospitals.

PMID- 27030807
TI  - In-vitro cell treatment with focused shockwaves-influence of the experimental
      setup on the sound field and biological reaction.
AB  - BACKGROUND: To improve understanding of shockwave therapy mechanisms, in vitro
      experiments are conducted and the correlation between cell reaction and shockwave
      parameters like the maximum pressure or energy density is studied. If the
      shockwave is not measured in the experimental setup used, it is usually assumed
      that the device's shockwave parameters (=manufacturer's free field measurements)
      are valid. But this applies only for in vitro setups which do not modify the
      shockwave, e.g., by reflection or refraction. We hypothesize that most setups
      used for in vitro shockwave experiments described in the literature influence the
      sound field significantly so that correlations between the physical parameters
      and the biological reaction are not valid. METHODS: To reveal the components of
      common shockwave in vitro setups which mainly influence the sound field, 32
      publications with 37 setups used for focused shockwave experiments were reviewed
      and evaluated regarding cavitation, cell container material, focal sound field
      size relative to cell model size, and distance between treated cells and air. For
      further evaluation of the severity of those influences, experiments and
      calculations were conducted. RESULTS: In 37 setups, 17 different combinations of
      coupling, cell container, and cell model are described. The setup used mainly is
      a transducer coupled via water to a tube filled with a cell suspension. As
      changes of the shockwaves' maximum pressure of 11 % can already induce changes of
      the biological reaction, the sound field and biological reactions are mainly
      disturbed by use of standard cell containers, use of coupling gel, air within the
      5 MPa focal zone, and cell model sizes which are bigger than half the -6 dB focal
      dimensions. CONCLUSIONS: Until now, correct and sufficient information about the
      shockwave influencing cells in vitro is only provided in 1 of 32 publications.
      Based on these findings, guidelines for improved in vitro setups are proposed
      which help minimize the influence of the setup on the sound field.

PMID- 27030808
TI  - Azoospermia in rabbits following an intravas injection of Vasalgel TM.
AB  - BACKGROUND: Vasectomy is currently the only long-acting contraceptive option
      available for men, despite increasing demand and potentially significant positive
      impacts on human health of additional male contraceptive options. Vasalgel TM is
      a high molecular weight hydrogel polymer being developed as a non-hormonal long
      acting reversible male contraceptive. Vasalgel consists of styrene-alt-maleic
      acid dissolved in dimethyl sulfoxide, which is distinct from styrene-alt-maleic
      anhydride materials previously studied. METHODS: The goal of the study was to
      determine the contraceptive efficacy of two test articles with different levels
      of styrene maleic acid (100 %, and 80 % acid/20 % anhydride). The test articles
      were injected bilaterally in the vasa deferentia of mature male rabbits. Post
      implantation analyses of semen parameters were completed over a 12 month period
      and compared to baseline measures of sperm concentration, motility and forward
      progression. RESULTS: Both test articles were effective in blocking the passage
      of spermatozoa through the vasa deferentia in the 12 subjects completing the
      study. A significant decrease in sperm concentration occurred following
      implantation of the test material, with no measurable sperm concentration except
      for a few samples in one animal that were markedly oligospermic. Vasalgel
      produced a rapid onset of azoospermia, with no sperm in semen samples collected
      as early as 29-36 days post-implantation, and was durable over a 12 month period.
      CONCLUSION: This study indicated that Vasalgel is an effective non-hormonal long
      acting male contraceptive in a rabbit model.

PMID- 27030809
TI  - Mechanisms of wound closure following acute arm injury in Octopus vulgaris.
AB  - BACKGROUND: Octopoda utilise their arms for a diverse range of functions,
      including locomotion, hunting, defence, exploration, reproduction, and grooming.
      However the natural environment contains numerous threats to the integrity of
      arms, including predators and prey during capture. Impressively, octopoda are
      able to close open wounds in an aquatic environment and can fully regenerate
      arms. The regrowth phase of cephalopod arm regeneration has been grossly
      described; however, there is little information about the acute local response
      that occurs following an amputation injury comparable to that which frequently
      occurs in the wild. METHODS: Adult Octopus vulgaris caught in the Bay of Naples
      were anaesthetised, the distal 10 % of an arm was surgically amputated, and
      wounded tissue was harvested from animals sacrificed at 2, 6, and 24 h post
      amputation. The extent of wound closure was quantified, and the cell and tissue
      dynamics were observed histologically, by electron microscopy, as well as using
      ultrasound. RESULTS: Macroscopic, ultrasonic and ultrastructural analyses showed
      extensive and significant contraction of the wound margins from the earliest time
      point, evidenced by tissue puckering. By 6 h post amputation, the wound was 64.0
      +/- 17.2 % closed compared to 0 h wound area. Wound edge epithelial cells were
      also seen to be migrating over the wound bed, thus contributing to tissue repair.
      Temporary protection of the exposed tip in the form of a cellular, non-mucus plug
      was observed, and cell death was apparent within two hours of injury. At earlier
      time-points this was apparent in the skin and deeper muscle layers, but
      ultimately extended to the nerve cord by 24 h. CONCLUSIONS: This work has
      revealed that O. vulgaris ecologically relevant amputation wounds are rapidly
      repaired via numerous mechanisms that are evolutionarily conserved. The findings
      provide insights into the early processes of repair preparatory to regeneration.
      The presence of epithelial, chromatophore, vascular, muscle and neural tissue in
      the arms makes this a particularly interesting system in which to study acute
      responses to injury and subsequent regeneration.

PMID- 27030810
TI  - Defining Molecular Basis for Longevity Traits in Natural Yeast Isolates.
AB  - The budding yeast has served as a useful model organism in aging studies, leading
      to the identification of genetic determinants of longevity, many of which are
      conserved in higher eukaryotes. However, factors that promote longevity in
      laboratory setting often have severe fitness disadvantage in the wild. Here, to
      obtain an unbiased view on longevity regulation we analyzed how replicative
      lifespan is shaped by transcriptional, translational, metabolic, and
      morphological factors across 22 wild-type Saccharomyces cerevisiae isolates. We
      observed significant differences in lifespan across these strains and found that
      their longevity is strongly associated with up-regulation of oxidative
      phosphorylation and respiration and down-regulation of amino acid and nitrogen
      compound biosynthesis. Since calorie restriction and TOR signaling also extend
      lifespan by adjusting many of the identified pathways, the data suggest that
      natural plasticity of yeast lifespan is shaped by processes that not only do not
      impose cost on fitness, but are amenable to dietary intervention.

PMID- 27030812
TI  - Pancreatic Cancer Exosomes: Shedding Off for a Meaningful Journey.

PMID- 27030811
TI  - Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1.
AB  - The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis.
      However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we
      identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are
      dramatically elevated with a strong positive correlation in colon cancer tissues.
      USP22 stabilizes CCNB1 by antagonizing proteasome-mediated degradation in a cell
      cycle-specific manner. Phosphorylation of USP22 by CDK1 enhances its activity in
      deubiquitinating CCNB1. The ubiquitin ligase anaphase-promoting complex (APC/C)
      targets USP22 for degradation by using the substrate adapter CDC20 during cell
      exit from M phase, presumably allowing CCNB1 degradation. Finally, we discover
      that USP22 knockdown leads to slower cell growth and reduced tumor size. Our
      study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that
      targeting USP22 might be an effective approach to treat cancers with elevated
      CCNB1 expression.

PMID- 27030813
TI  - Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased
      survival in ovarian cancer patients.
AB  - BACKGROUND: Malnutrition, weight loss, and muscle wasting (sarcopenia) are common
      among women with advanced ovarian cancer and have been associated with adverse
      clinical outcomes and survival. Our objective is to investigate overall survival
      (OS) related to changes in skeletal muscle (SM) for patients with advanced
      ovarian cancer treated with neoadjuvant chemotherapy and interval debulking.
      METHODS: Ovarian cancer patients (n = 123) treated with neoadjuvant chemotherapy
      and interval debulking in the area of Maastricht (the Netherlands) between 2000
      and 2014 were included retrospectively. Surface areas of SM and adipose tissue
      were defined on computed tomography at the level of the third lumbar vertebra.
      Low SM at baseline and SM changes during chemotherapy were compared with Kaplan
      Meier curves, and Cox-regression models were applied to test predictors of OS.
      RESULTS: Median OS for patients who lost SM (n = 83) was 916 +/- 99 days, which
      was significantly different from median OS for patients who maintained or gained
      SM (n = 40), which was 1431 +/- 470 days (P = 0.004). Loss of SM was also a
      significant predictor of OS in multivariable Cox-regression analysis (hazard
      ratio 1.773 (95%CI: 1.018-3.088), P = 0.043). Low baseline SM did not influence
      survival. CONCLUSIONS: Patients with ovarian cancer have a worse survival when
      they lose SM during neoadjuvant chemotherapy. Evaluation of low SM at a specific
      time point is not prognostic for OS. External and prospective validation of these
      findings is imperative. Nutritional, pharmacological, and/or physical
      intervention studies are necessary to establish whether SM impairment can be
      prevented to prolong ovarian cancer survival.

PMID- 27030814
TI  - Discussion around statin discontinuation in older adults and patients with
      wasting diseases.

PMID- 27030816
TI  - Nutrition in cachexia: from bench to bedside.
AB  - As malnutrition is often present in cachexia, nutritional intervention has been
      one of the widely accepted strategies. A literature review of cachexia models
      with dietary interventions in the present issue of this journal pointed out that
      the majority of nutrient intervention studies were of n-3 fatty acid, mainly
      eicosapentaenoic acid and docosahexaenoic acid. Effect on protein catabolism and
      anti-inflammation are most pronounced benefits of n-3 fatty acid. The
      effectiveness of n-3 fatty acid may depend on control diet or even be attributed
      to the polyunsaturated fatty acid deficiency inadvertently produced in control
      group. However, there is not enough clinical evidence to support a benefit of n-3
      fatty acid substitution in patients with cachexia. The second important result
      from this review is that the majority of studies did not provide information
      about dietary design or did not standardize design, content, source, and overall
      composition. To guide dietary design for researchers in preclinical studies, a
      model has been proposed in this review, which may be useful to predict the
      efficacy of new dietary intervention in cachexia science. From a clinical point
      of view, the limited effectiveness of nutritional support in cachexia may partly
      be explained by the multifactorial nature of this condition. Cachexia differs
      from malnutrition inasmuch as malnutrition can be reversed by adequate nutrition
      and/or by overcoming problems of absorption or utilization of nutrients, but
      cachexia cannot be successfully treated by nutrition alone. Multidisciplinary
      approach including the assessment and intervention in feeding, appetite,
      swallowing, exercise, psychosocial, and psychological issue may be needed to
      improve nutrition in patients with cachexia. 

PMID- 27030815
TI  - Dysfunction of respiratory muscles in critically ill patients on the intensive
      care unit.
AB  - Muscular weakness and muscle wasting may often be observed in critically ill
      patients on intensive care units (ICUs) and may present as failure to wean from
      mechanical ventilation. Importantly, mounting data demonstrate that mechanical
      ventilation itself may induce progressive dysfunction of the main respiratory
      muscle, i.e. the diaphragm. The respective condition was termed 'ventilator
      induced diaphragmatic dysfunction' (VIDD) and should be distinguished from
      peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'.
      Interestingly, VIDD and ICU-AW may often be observed in critically ill patients
      with, e.g. severe sepsis or septic shock, and recent data demonstrate that the
      pathophysiology of these conditions may overlap. VIDD may mainly be characterized
      on a histopathological level as disuse muscular atrophy, and data demonstrate
      increased proteolysis and decreased protein synthesis as important underlying
      pathomechanisms. However, atrophy alone does not explain the observed loss of
      muscular force. When, e.g. isolated muscle strips are examined and force is
      normalized for cross-sectional fibre area, the loss is disproportionally larger
      than would be expected by atrophy alone. Nevertheless, although the exact
      molecular pathways for the induction of proteolytic systems remain incompletely
      understood, data now suggest that VIDD may also be triggered by mechanisms
      including decreased diaphragmatic blood flow or increased oxidative stress. Here
      we provide a concise review on the available literature on respiratory muscle
      weakness and VIDD in the critically ill. Potential underlying pathomechanisms
      will be discussed before the background of current diagnostic options.
      Furthermore, we will elucidate and speculate on potential novel future
      therapeutic avenues.

PMID- 27030817
TI  - Nutritional leucine supplementation attenuates cardiac failure in tumour-bearing
      cachectic animals.
AB  - BACKGROUND: The condition known as cachexia presents in most patients with
      malignant tumours, leading to a poor quality of life and premature death.
      Although the cancer-cachexia state primarily affects skeletal muscle, possible
      damage in the cardiac muscle remains to be better characterized and elucidated.
      Leucine, which is a branched chain amino acid, is very useful for preserving lean
      body mass. Thus, this amino acid has been studied as a coadjuvant therapy in
      cachectic cancer patients, but whether this treatment attenuates the effects of
      cachexia and improves cardiac function remains poorly understood. Therefore,
      using an experimental cancer-cachexia model, we evaluated whether leucine
      supplementation ameliorates cachexia in the heart. METHODS: Male Wistar rats were
      fed either a leucine-rich or a normoprotein diet and implanted or not with
      subcutaneous Walker-256 carcinoma. During the cachectic stage (approximately 21
      days after tumour implantation), when the tumour mass was greater than 10% of
      body weight, the rats were subjected to an electrocardiogram analysis to evaluate
      the heart rate, QT-c, and T wave amplitude. The myocardial tissues were assayed
      for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and
      calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of
      metalloproteinases, and total plasminogen activator inhibitor 1), and caspase-8, 
      9, -3, and -7 activity. RESULTS: Both groups of tumour-bearing rats, especially
      the untreated group, had electrocardiography alterations that were suggestive of
      ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats
      in the untreated tumour-bearing group but not their leucine-supplemented
      littermates exhibited remarkable increases in chymotrypsin activity and all three
      heart failure biomarkers analysed, including an increase in caspase-3 and -7
      activity. CONCLUSIONS: Our data suggest that a leucine-rich diet could modulate
      heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer-cachexia.
      Further studies must be conducted to elucidate leucine's mechanisms of action,
      which potentially includes the modulation of the heart's inflammatory process.

PMID- 27030819
TI  - The ZmRCP-1 promoter of maize provides root tip specific expression of transgenes
      in plantain.
AB  - BACKGROUND: Bananas and plantains (Musa spp.) provide 25 % of the food energy
      requirements for more than 100 million people in Africa. Plant parasitic
      nematodes cause severe losses to the crop due to lack of control options. The
      sterile nature of Musa spp. hampers conventional breeding but makes the crop
      suitable for genetic engineering. A constitutively expressed synthetic peptide in
      transgenic plantain has provided resistance against nematodes. Previous work with
      the peptide in potato plants indicates that targeting expression to the root tip
      improves the efficacy of the defence mechanism. However, a promoter that will
      provide root tip specific expression of transgenes in a monocot plant, such as
      plantain, is not currently available. Here, we report the cloning and evaluation
      of the maize root cap-specific protein-1 (ZmRCP-1) promoter for root tip targeted
      expression of transgenes that provide a defence against plant parasitic nematodes
      in transgenic plantain. RESULTS: Our findings indicate that the maize ZmRCP-1
      promoter delivers expression of beta-glucuronidase (gusA) gene in roots but not
      in leaves of transgenic plantains. In mature old roots, expression of gusA gene
      driven by ZmRCP-1 becomes limited to the root cap. Invasion by the nematode
      Radopholus similis does not modify Root Cap-specific Protein-1 promoter activity.
      CONCLUSIONS: Root cap-specific protein-1 promoter from maize can provide targeted
      expression of transgene for nematode resistance in transgenic plantain.

PMID- 27030818
TI  - Plasma in dentistry.
AB  - This review describes the contemporary aspects of plasma application in
      dentistry. Previous studies on plasma applications were classified into two
      categories, surface treatment and direct applications, and were reviewed,
      respectively according to the approach. The current review discussed modification
      of dental implant surface, enhancing of adhesive qualities, enhancing of
      polymerization, surface coating and plasma cleaning under the topics of surface
      treatment. Microbicidal activities, decontamination, root canal disinfection and
      tooth bleaching were reviewed as direct applications with other miscellaneous
      ones. Non-thermal atmospheric pressure plasma was of particular focus since it is
      gaining considerable attention due to the possibility for its use in living
      tissues. Future perspectives have also been discussed briefly. Although it is
      still not popular among dentists, plasma has shown promises in several areas of
      dentistry and is now opening a new era of plasma dentistry.

PMID- 27030820
TI  - Calcium vitamin D3 supplementation in clinical practice: side effect and
      satisfaction.
AB  - BACKGROUND: The objective of this study was to assess side effects and
      satisfaction about OsteoCalVitFort (500 mg calcium and 400 I.U. of vitamin D3)
      usage. METHODS: A total 186 people were participated with range age from 18 to 65
      years old. Each participant received 1 pack that contains 60 OsteoCalVitFort
      tablet and used two tablet OsteoCalVitFort daily (1 tablet after breakfast and 1
      after dinner). By a phone call, side effects and satisfaction about
      OsteoCalVitFort were assessed. RESULTS: The rate of constipating (8.0 %) and
      bloating (12.5 %) were decreased significantly after OsteoCalVitFort supplement
      intake (1.2 %, and 0.6 %, respectively). Similar results were observed in
      metallic taste in mouth, tiredness, weakness, loss of appetite, bone/muscle pain
      and mental/mood change after Calcium Vitamin D3 supplementation intake. Totally,
      94 % of patients were satisfied about OsteoCalVitFort usage. CONCLUSION: The
      results of the research indicate despite the high quality of OsteoCalVitFort
      supplement, there are no side effects which have been seen in other supplements.

PMID- 27030821
TI  - Combined association analysis of interleukin 1-receptor antagonist (IL-1RN)
      variable number of tandem repeat (VNTR) and Haptoglobin 1/2 polymorphisms with
      type 2 diabetes mellitus risk.
AB  - BACKGROUND: The polymorphism of Interleukin 1 receptor antagonist gene (IL-1RN),
      which encodes a natural antagonist of pro-inflammatory cytokines belonging to IL
      1 family and Haptoglobin (HP) have been studied in various ethnic groups in
      association with Type 2 Diabetes Mellitus (T2DM) risk and related complications.
      However, there was no study available among the Emirati population. Hence, we
      designed a combined study on IL-1RN and HP polymorphism to evaluate their
      association with prevalence of T2DM, related complication and hypertension and
      also its interaction with obesity status among Emirati population. METHODS: IL
      1RN and HP genotypes were determined in total 487 Emiratis divided in two groups
      of T2DM case (n = 271) and healthy controls (n = 215) by polymerase chain
      reaction (PCR) followed by gel electrophoresis. Gene-gene interaction and
      polymorphism-obesity interaction were determined by multivariate logistic
      regression analysis. RESULTS: We found that the frequencies of IL-1RN*1/*1 and
      HP2-2 genotypes were significantly higher in cases than control and were
      associated with increased T2DM risk with an odds ratio (OR) of 1.60 (95 % CI 1.10
      2.36) and 1.63 (95 % CI 1.11-2.64), respectively. The association lack any
      interaction with obesity status. Associations with occurrences of T2DM related
      complications and hypertension were not observed. CONCLUSIONS: We report an
      association of IL-1RN and HP polymorphism with T2DM risk independent of each
      other and of obesity status but no association with related complications and
      hypertension.

PMID- 27030823
TI  - Clinical Comorbidities among Cocaine Users Screened in the Community through
      HealthStreet.
AB  - OBJECTIVES: We investigated the differences in clinical characteristics and
      musculoskeletal (MSK) conditions by cocaine use. METHODS: HealthStreet, a
      community engagement program assessed 7936 adults for medical conditions.
      RESULTS: Among 6145 African Americans (77%) and 1791 (23%) Caucasians, 15.5 % and
      25% reported cocaine use, respectively. African-American cocaine users were older
      (p < .001) and more likely to report hypertension (p < .001) and HIV (p <.001)
      than Caucasian users. Compared to non-users, back pain was reported by 42% of
      African Americans (p < .001) and 48% of Caucasian cocaine users (p < .003).
      African-American cocaine users had significantly higher odds of back pain, 1.60
      (95% CI 1.27, 2.04) and arthritis, 1.40 (95% CI 1.19, 1.64) than Caucasians.
      CONCLUSIONS: Cocaine users are more likely to endorse MSK conditions than non
      users. Racial disparities among users existed; however, how race affects health
      among users requires further research.

PMID- 27030824
TI  - In vitro Ag Cross-presentation and in vivo Ag Cross-presentation by Dendritic
      Cells in the Mouse.
AB  - Antigen cross presentation is important for effective immune responses to tumors
      and viral infections. Dendritic cells are professional antigen presenting cells
      and are unique in their ability to cross-present exogenous antigens on MHC class
      I molecules and activate antigen specific cytotoxic T cells. This protocol
      describes antigen cross presentation by dendritic cells (DCs) (bone marrow
      derived DCs and splenic DCs) in an in vitro and in an in vivo assay system using
      soluble ovalbumin protein.

PMID- 27030822
TI  - Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the
      Retina and Brain?
AB  - Epidemiological studies demonstrate that a high dietary intake of carotenoids may
      offer protection against age-related macular degeneration, cancer and
      cardiovascular and neurodegenerative diseases. Humans cannot synthesize
      carotenoids and depend on their dietary intake. Major carotenoids that have been
      found in human plasma can be divided into two groups, carotenes (nonpolar
      molecules, such as beta-carotene, alpha-carotene or lycopene) and xanthophylls
      (polar carotenoids that include an oxygen atom in their structure, such as
      lutein, zeaxanthin and beta-cryptoxanthin). Only two dietary carotenoids, namely
      lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the
      human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the
      human retina from lutein. Additionally, xanthophylls account for about 70% of
      total carotenoids in all brain regions. Some specific properties of these polar
      carotenoids must explain why they, among other available carotenoids, were
      selected during evolution to protect the retina and brain. It is also likely that
      the selective uptake and deposition of macular xanthophylls in the retina and
      brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that
      the high membrane solubility and preferential transmembrane orientation of
      macular xanthophylls distinguish them from other dietary carotenoids, enhance
      their chemical and physical stability in retina and brain membranes and maximize
      their protective action in these organs. Most importantly, xanthophylls are
      selectively concentrated in the most vulnerable regions of lipid bilayer
      membranes enriched in polyunsaturated lipids. This localization is ideal if
      macular xanthophylls are to act as lipid-soluble antioxidants, which is the most
      accepted mechanism through which lutein and zeaxanthin protect neural tissue
      against degenerative diseases.

PMID- 27030825
TI  - Fulfilling the Promise of Microbiomics to Revolutionize Medicine.

PMID- 27030826
TI  - Conclusions: From peer to peer communication to communicating with policymakers
      and the general public.

PMID- 27030827
TI  - Morphing into Mini.

PMID- 27030828
TI  - Dynamic quantification of antigen molecules with flow cytometry.
AB  - Traditional methods for estimating the number of expressed molecules, based on
      the detection of target antigens bound with fluorescently labeled antibodies,
      assume that the antigen-antibody reaction reaches equilibrium. A calibration
      procedure is used to convert the intensity of the fluorescence signal to the
      number of target molecules. Along with the different limitations of every
      calibration system, this substantially limits the applicability of the
      traditional approaches especially in the case of low affinity antibodies. We
      address this problem here with studies in which we demonstrate a new approach to
      the antigen molecule quantification problem. Instead of using a static
      calibration system, we analyzed mean fluorescence values over time by flow
      cytometry during antibody-antigen binding. Experimental data obtained with an
      LSRII cytometer were fitted by a diffusion-reaction mathematical model using the
      Levenberg-Marquardt nonlinear least squares curve-fitting algorithm in order to
      obtain the number of target antigen molecules per cell. Results were compared
      with the Quanti-BRITE calibration system. We conclude that, instead of using
      experiment-specific calibration, the value of the binding rate constant for each
      particular antibody-antigen reaction can be used to quantify antigen molecules
      with flow cytometry. The radius of CD8 antibody molecule binding site was found,
      that allows recalculating the binding rate constant for other conditions
      (different sizes of reagent molecules, fluorescent label, medium viscosity and
      temperature). This approach is independent of specially prepared calibration
      beads, antibody reagents and the specific dye and can be applied to both low and
      high affinity antibodies, under both saturating and non-saturating binding
      conditions. The method was demonstrated on a human blood sample dataset
      investigating CD8alpha antigen on T cells in stable binding conditions.

PMID- 27030829
TI  - Authors' reply.

PMID- 27030830
TI  - Authors' reply.

PMID- 27030831
TI  - [Neuroanatomical age-related changes in apathy].
AB  - The introduction of new instrumental methods, in particular neuroimaging
      techniques, in academic studies and clinical practice allowed to identify
      neuroanatomical and functional correlates of different clinical syndromes.
      Authors summarized the results of magnetic-resonance tomography (MRI) and one
      photon emission computed tomography (OPECT) studies of apathy of old-age
      developed in the structure of different neurological and mental diseases. The
      literature over that last two decades was reviewed

PMID- 27030832
TI  - WHY THE RARE DISEASES BECOME TO BE A CHALLENGE FOR MEDICINE OF TODAY?

PMID- 27030833
TI  - Reply: To PMID 26248348.

PMID- 27030834
TI  - [Current approaches to treatment of migraine during pregnancy].
AB  - Migraine is one of the most common complaints in the majority of pregnant women.
      Migraine without aura is the most frequent cause of headache. Improvement of this
      disease is reported in 50-80% of patient. However, about one third of pregnant
      women have severe prolonged attacks with marked concomitant symptoms and
      maladaptation that necessarily need treatment. Authors consider the issues of
      differential diagnosis and principles of management of these patients.

PMID- 27030835
TI  - [Maternal alcoholism and its impact on child health].
AB  - Maternal alcoholism hinders the normal development of child and threatens his
      mental and physical health due to three factors: the hereditary transmission of
      predisposition to alcohol abuse; alcohol consumption during pregnancy; adverse
      family environment. The children of mothers suffering from alcoholism revealed
      are characterized by increased risk of depression, anxiety and other mental
      disorders, including alcohol and substance dependence. The adverse impact of
      maternal alcoholism (or, to speak more widely, parents' alcoholism) on the child
      health requires special preventive and treatment programs for both parents and
      children. Separation from the mother (even if the mother is addicted to alcohol)
      seriously injures the child, and therefore treatment programs for alcohol abusing
      women should be focused on the possible continuation of the parental rights of
      patients.

PMID- 27030836
TI  - [Obituary: Professor Rene Loubet (1925-2015)].

PMID- 27030837
TI  - [Trigeminal autonomic cephalgias].
AB  - Review of literature on the trigeminal autonomic cephalgias are presented.
      Trigeminal autonomic cephalgias are primary headaches with phenotype consisting
      of trigeminal pain with autonomic sign including lacrimation, rhinorrhea and
      miosis. Discussed are issues of classification, pathogenesis, clinical picture,
      diagnosis, differential diagnosis and treatment of this headache. Special
      attention is paid to cluster headache, paroxysmal hemicrania, SUNCT syndrome,
      hemicrania continua.

PMID- 27030838
TI  - [Tanakan as a multimodal cytoprotective factor in general medicine].
AB  - The first section of the review provides recent results regarding the mechanism
      of the action of a standardized extract of ginkgo biloba leaves EGb761 (tanakan),
      its effects on apoptosis, neuroplasticity, hemorheology, inhibition of the
      amyloid genesis and inflammatory response it cause, activation of proteasomes in
      conformational diseases. Current experimental and clinical results suggest that
      EGb761 (tanakan) is a high-effective cytoprotective agent in cognitive disorders
      of various genesis, cardiovascular diseases (in the process of rehabilitation and
      as a medicine capable to reduce the volume of brain damage in stroke). The effect
      of tanakan on anxiety and depression in patients with cognitive impairment should
      be considered as clinically significant.

PMID- 27030839
TI  - The herbarium sheet.

PMID- 27030840
TI  - Nobody on the face of the globe lived longer.

PMID- 27030841
TI  - Authors' reply.

PMID- 27030842
TI  - Effects of age on the pharmacokinetics of tramadol and its active metabolite, O
      desmethyltramadol following intravenous administration to foals.
AB  - REASONS FOR PERFORMING STUDY: Tramadol is an analgesic agent used in man and a
      number of veterinary species. The pharmacokinetics and behavioural effects of
      tramadol and its active metabolite have been described in mature horses, but not
      in young foals. OBJECTIVES: To characterise the pharmacokinetics, metabolism and
      some induced behavioural and physiological responses following i.v. tramadol
      administration in the same group of foals on 4 different occasions, from a few
      days after birth to age 43 days. STUDY DESIGN: Experimental. METHODS: Tramadol
      was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasions
      at ages 6-8, 13-15, 20-22 and 40-43 days. Blood samples were collected prior to
      administration and at multiple times until 48 h post administration. Blood
      samples were analysed for tramadol and metabolite concentrations and
      pharmacokinetics determined at each age. Behavioural and physiological effects
      were also assessed. RESULTS: The average volume of distribution was 5.10, 4.63,
      4.02 and 3.84 l/kg bwt and clearance 3.44, 3.08, 3.14 and 2.69 l/h/kg bwt when
      foals were aged 6-8, 13-15, 20-22 and 40-43 days, respectively. There was not a
      significant difference in the elimination half-life between age groups (1.52,
      1.73, 1.13 and 1.51 for ages 6-8, 13-15, 20-22 and 40-43 days, respectively). The
      metabolites produced were the same as in mature horses; however, glucuronidation
      capability, appeared to increase with increasing age. Tramadol administration was
      well tolerated at all ages studied with sedation noted in the 3 older age groups.
      CONCLUSIONS: Tramadol appears to be consistently well tolerated following i.v.
      administration of 3 mg/kg bwt to foals ranging in age from 1 to 6 weeks. Although
      analgesic concentrations in foals have yet to be established, the results of this
      study support further study of tramadol for clinical use in foals.

PMID- 27030843
TI  - Authors' reply.

PMID- 27030844
TI  - Action Recognition Using Rate-Invariant Analysis  of Skeletal Shape Trajectories.
AB  - We study the problem of classifying actions of human subjects using depth movies
      generated by Kinect or other depth sensors. Representing human body as dynamical
      skeletons, we study the evolution of their (skeletons') shapes as trajectories on
      Kendall's shape manifold. The action data is typically corrupted by large
      variability in execution rates within and across subjects and, thus, causing
      major problems in statistical analyses. To address that issue, we adopt a
      recently-developed framework of Su et al. [1], [2] to this problem domain. Here,
      the variable execution rates correspond to re-parameterizations of trajectories,
      and one uses a parameterization-invariant metric for aligning, comparing,
      averaging, and modeling trajectories. This is based on a combination of
      transported square-root vector fields (TSRVFs) of trajectories and the standard
      Euclidean norm, that allows computational efficiency. We develop a comprehensive
      suite of computational tools for this application domain: smoothing and denoising
      skeleton trajectories using median filtering, up- and down-sampling actions in
      time domain, simultaneous temporal-registration of multiple actions, and
      extracting invertible Euclidean representations of actions. Due to invertibility
      these Euclidean representations allow both discriminative and generative models
      for statistical analysis. For instance, they can be used in a SVM-based
      classification of original actions, as demonstrated here using MSR Action-3D, MSR
      Daily Activity and 3D Action Pairs datasets. Using only the skeletal information,
      we achieve state-of-the-art classification results on these datasets.

PMID- 27030845
TI  - Associate Professor Nigel Clarke PhD, MBChB, FRACP (1966-2015).

PMID- 27030846
TI  - Knee joint contact mechanics during downhill gait and its relationship with
      varus/valgus motion and muscle strength in patients with knee osteoarthritis.
AB  - OBJECTIVE: The objective of this exploratory study was to evaluate tibiofemoral
      joint contact point excursions and velocities during downhill gait and assess the
      relationship between tibiofemoral joint contact mechanics with frontal-plane knee
      joint motion and lower extremity muscle weakness in patients with knee
      osteoarthritis (OA). METHODS: Dynamic stereo X-ray was used to quantify
      tibiofemoral joint contact mechanics and frontal-plane motion during the loading
      response phase of downhill gait in 11 patients with knee OA and 11 control
      volunteers. Quantitative testing of the quadriceps and the hip abductor muscles
      was also performed. RESULTS: Patients with knee OA demonstrated larger
      medial/lateral joint contact point excursions (p < 0.02) and greater heel-strike
      joint contact point velocities (p < 0.05) for the medial and lateral compartments
      compared to the control group. The peak medial/lateral joint contact point
      velocity of the medial compartment was also greater for patients with knee OA
      compared to their control counterparts (p = 0.02). Additionally, patients with
      knee OA demonstrated significantly increased frontal-plane varus motion
      excursions (p < 0.01) and greater quadriceps and hip abductor muscle weakness (p
      = 0.03). In general, increased joint contact point excursions and velocities in
      patients with knee OA were linearly associated with greater frontal-plane varus
      motion excursions (p < 0.04) but not with quadriceps or hip abductor strength.
      CONCLUSION: Altered contact mechanics in patients with knee OA may be related to
      compromised frontal-plane joint stability but not with deficits in muscle
      strength.

PMID- 27030847
TI  - Bone of my bones.

PMID- 27030848
TI  - Paul Ichiro Terasaki.

PMID- 27030849
TI  - Author Response.

PMID- 27030850
TI  - Author Response.

PMID- 27030851
TI  - Retraction notice to "The rapid and sustained  responses of dendritic cells to
      influenza virus  infection in a non-human primate model"  [Braz. J. Infect. Dis.
      18 (2014) 406-413].

PMID- 27030879
TI  - Ambulatory Surgery Center Experience: Perioperative Complications After Cervical
      High-Grade Squamous Intraepithelial Lesion Excision.

PMID- 27030880
TI  - Endometriosis of the Perineum: A Rare Diagnosis Usually Associated With
      Episiotomy.

PMID- 27030881
TI  - Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.
AB  - OBJECTIVE: The aim of the study was to evaluate the surgical management and the
      role of different prognostic factors on survival outcomes of women affected by
      genital (i.e., vulvar and vaginal) melanoma. MATERIALS AND METHODS: Data of
      patients undergoing primary surgical treatment for genital melanoma were
      evaluated in this retrospective study. Baseline, pathological, and postoperative
      variables were tested to identify prognostic factors. Five-year disease-free
      survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox
      proportional hazards models. RESULTS: Overall, 98 patients met the inclusion
      criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were
      diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and
      OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors
      influencing DFS, we observed that at multivariate analysis, only vaginal
      localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses
      (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal
      status was the only independent factor influencing 5-year OS in patients with
      vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI =
      1.08-12.3; p = .03) melanoma. CONCLUSIONS: Genital melanomas are characterized by
      a poor prognosis. Number of mitoses and lymph node status are the main factors
      influencing survival. Surgery is the mainstay of treatment. A correct and prompt
      diagnosis is paramount.

PMID- 27030882
TI  - Vulvar Exacerbation of Epidermolysis Bullosa Simplex: A Case Report.

PMID- 27030883
TI  - Clinical Performance Validation of 4 Point-of-Care Cervical Cancer Screening
      Tests in HIV-Infected Women in Zambia.
AB  - OBJECTIVES: We sought to determine the clinical performance of visual inspection
      with acetic acid (VIA), digital cervicography (DC), Xpert human papillomavirus
      (HPV), and OncoE6 for cervical cancer screening in an HIV-infected population.
      MATERIALS AND METHODS: HIV-infected women 18 years or older were included in this
      cross-sectional validation study conducted in Lusaka, Zambia. The screening tests
      were compared against a histological gold standard. We calculated sensitivity,
      specificity, positive and negative predictive values, positive and negative
      likelihood ratios, and odds ratios using cervical intraepithelial neoplasia grade
      2 or worse (CIN 2+) and grade 3 or worse (CIN 3+) thresholds. RESULTS: Between
      January and June 2015, a total of 200 women were enrolled. Fifteen percent were
      screen positive by VIA, 20% by DC, 47% by Xpert HPV, and 6% by OncoE6. Using a
      CIN 2+ threshold, the sensitivity and specificity of VIA were 48% (95% CI = 30%
      67%) and 92% (95% CI = 86%-95%), respectively. Similarly, the sensitivity and
      specificity of DC were 59% (95% CI = 41%-76%) and 88% (95% CI = 82%-93%),
      respectively. The sensitivity and specificity of Xpert HPV were 88% (95% CI = 71%
      97%) and 60% (95% CI = 52%-68%), respectively. Finally, the sensitivity and
      specificity of OncoE6 were 31% (95% CI = 16%-50%) and 99% (95% CI = 97%-100%),
      respectively. CONCLUSIONS: VIA and DC displayed moderate sensitivity and high
      specificity. Xpert HPV performed equivalently to currently approved HPV DNA
      tests, with high sensitivity and moderate specificity. OncoE6 displayed excellent
      specificity but low sensitivity. These results confirm an important role for VIA,
      DC, and Xpert HPV in screen-and-treat cervical cancer prevention in low- and
      middle-income countries, such as Zambia.

PMID- 27030884
TI  - mHealth to Train Community Health Nurses in Visual Inspection With Acetic Acid
      for Cervical Cancer Screening in Ghana.
AB  - OBJECTIVE: There is a shortage of trained health care personnel for cervical
      cancer screening in low-/middle-income countries. We evaluated the feasibility
      and limited efficacy of a smartphone-based training of community health nurses in
      visual inspection of the cervix under acetic acid (VIA). MATERIALS AND METHODS:
      During April to July 2015 in urban Ghana, we designed and developed a study to
      determine the feasibility and efficacy of an mHealth-supported training of
      community health nurses (CHNs, n = 15) to perform VIA and to use smartphone
      images to obtain expert feedback on their diagnoses within 24 hours and to
      improve VIA skills retention. The CHNs completed a 2-week on-site introductory
      training in VIA performance and interpretation, followed by an ongoing 3-month
      text messaging-supported VIA training by an expert VIA reviewer. RESULTS:
      Community health nurses screened 169 women at their respective community health
      centers while receiving real-time feedback from the reviewer. The total agreement
      rate between all VIA diagnoses made by all CHNs and the expert reviewer was 95%.
      The mean (SD) rate of agreement between each CHN and the expert reviewer was
      89.6% (12.8%). The agreement rates for positive and negative cases were 61.5% and
      98.0%, respectively. Cohen kappa statistic was 0.67 (95% CI = 0.45-0.88). Around
      7.7% of women tested VIA positive and received cryotherapy or further services.
      CONCLUSIONS: Our findings demonstrate the feasibility and efficacy of mHealth
      supported VIA training of CHNs and have the potential to improve cervical cancer
      screening coverage in Ghana.

PMID- 27030885
TI  - Cooperative capture synthesis: yet another playground for copper-free click
      chemistry.
AB  - Click chemistry describes a family of modular, efficient, versatile and reliable
      reactions which have acquired a pivotal role as one of the most useful synthetic
      tools with a potentially broad range of applications. While copper(i)-catalysed
      alkyne-azide cycloaddition is the most widely adopted click reaction in the
      family, the fact that it is cytotoxic restricts its practice in certain
      situations, e.g., bioconjugation. Consequently, researchers have been exploring
      the development of copper-free click reactions, the most popular example so far
      being strain-promoted alkyne-azide cycloadditions. An early example of copper
      free click reactions that is rarely mentioned in the literature is the
      cucurbit[6]uril (CB6) catalysed alkyne-azide cycloaddition (CB-AAC). Despite the
      unique ability of CB-AAC to generate mechanically interlocked molecules (MIMs) -
      in particular, rotaxanes - its slow reaction rate and narrow substrate acceptance
      limit its scope. In this Tutorial Review, we describe our efforts of late in
      developing the fundamental principles and practical applications of a new copper
      free click reaction - namely, cooperative capture synthesis, whereby introducing
      a cyclodextrin (CD) as an accelerator in CB-AAC, hydrogen bonding networks are
      formed between the rims of CD and CB6 in a manner that is positively cooperative,
      giving rise to a high level of pre-organisation during efficient and quick
      rotaxane formation. For example, [4]rotaxanes can be prepared nearly
      quantitatively within a minute in water. Furthermore, we have demonstrated that
      CB-AAC can accommodate a wider substrate tolerance by introducing pillararenes as
      promoters. To date, we have put cooperative capture synthesis into practice by
      (i) preparing polyrotaxanes containing up to 200 rings in nearly quantitative
      yields, (ii) trapping conformational isomers of polymacrocycles as rings in
      rotaxanes, (iii) demonstrating solid-state fluorescence and Forster resonance
      energy transfer (FRET) processes by fixing the fluorophores in a rotaxane and
      (iv) establishing the principle of supramolecular encryption in the preparation
      of dynamically and reversibly tunable fluorescent security inks.

PMID- 27030886
TI  - A Nanowire-Based Plasmonic Quantum Dot Laser.
AB  - Quantum dots enable strong carrier confinement and exhibit a delta-function like
      density of states, offering significant improvements to laser performance and
      high-temperature stability when used as a gain medium. However, quantum dot
      lasers have been limited to photonic cavities that are diffraction-limited and
      further miniaturization to meet the demands of nanophotonic-electronic
      integration applications is challenging based on existing designs. Here we
      introduce the first quantum dot-based plasmonic laser to reduce the cross
      sectional area of nanowire quantum dot lasers below the cutoff limit of photonic
      modes while maintaining the length in the order of the lasing wavelength. Metal
      organic chemical vapor deposition grown GaAs-AlGaAs core-shell nanowires
      containing InGaAs quantum dot stacks are placed directly on a silver film, and
      lasing was observed from single nanowires originating from the InGaAs quantum dot
      emission into the low-loss higher order plasmonic mode. Lasing threshold pump
      fluences as low as ~120 MUJ/cm(2) was observed at 7 K, and lasing was observed up
      to 125 K. Temperature stability from the quantum dot gain, leading to a high
      characteristic temperature was demonstrated. These results indicate that high
      performance, miniaturized quantum dot lasers can be realized with plasmonics. 

PMID- 27030887
TI  - Diindenopyrenes: Extended 1,6- and 1,8-Pyrenoquinodimethanes with Singlet
      Diradical Characters.
AB  - Diindenopyrene 4b and its diastereomer, which are extended homologues of 1,6- and
      1,8-pyrenoquinodimethanes fused by indene units, respectively, were synthesized
      by reaction of 1,4,5,8-tetrakis(mesitylethynyl)naphthalene (7) with bis(2,4,6
      trimethylpyridine)iodine(I) hexafluorophosphate via cationic cyclization
      mechanisms at both centers of reaction. Unexpectedly, reaction of 7 with iodine,
      a reagent that typically gives products of cationic cyclization, gave
      cycloheptapentalenoindenophenalene derivative 9b and its diastereomer
      incorporating an azulene unit at one end of the pi framework, via two different
      modes (radical and cationic) of cyclization at each reaction site. The physical
      properties of the products are presented, and the dual modes of cyclization of 7
      and its model compound with only one reaction center are discussed.

PMID- 27030888
TI  - Effect of Gravity on the Configuration of Droplets on Two-Dimensional Physically
      Patterned Surfaces.
AB  - Wetting of solid surfaces is important for many potential applications, including
      the design of low-drag and antifouling/self-cleaning surfaces, and it is usually
      quantified by the contact angle and by contact angle hysteresis. Both the
      chemistry and the physical patterning of the surface are known to affect the
      contact angle. In studying the wetting of such surfaces, most models focus on the
      small Bond number (Bo) limit in which the effect of gravity is negligible, which
      simplifies free energy calculations. In this work, we employ a thermodynamic
      model for surfaces patterned with two-dimensional asperities, which remains
      applicable for nonzero Bo. We employ two versions of the model: one in which we
      require the liquid-vapor interface to remain a circular cap, and another in which
      we allow the liquid-vapor interface to deform. We find that the effects of
      gravity are twofold. First, drops with larger Bo tend to flatten and spread
      across the surface relative to the same size drops with Bo = 0. Second, gravity
      makes it more favorable for drops to penetrate surface asperities compared to the
      case of Bo = 0, which also tends to lower the contact angles. The main effect of
      droplet deformation is to produce larger contact angles for the same wetting
      configuration. Finally, we compare our model predictions with relevant
      experimental observations. We find very close agreement with the experiments,
      thereby validating our theoretical model.

PMID- 27030892
TI  - Hypophosphatasia: diagnosis and clinical signs - a dental surgeon perspective.
AB  - BACKGROUND: Hypophosphatasia (HPP) is a rare inherited metabolic disease in which
      mutations in the ALPL gene (encoding tissue-nonspecific alkaline phosphatase)
      result in varying degrees of enzyme deficiency. HPP manifests in a spectrum of
      symptoms, including early primary tooth loss (root intact) and alveolar bone
      mineralisation defects. OBJECTIVE: To provide an overview of HPP for dental
      professionals to help recognise and differentially diagnose patients for
      appropriate referral to a specialist team. METHODS: A non-systematic review of
      publications on HPP was performed. RESULTS: Different forms of HPP are described,
      along with characteristic symptoms and laboratory findings. Diagnosis is
      challenging due to the rareness and variable presentation of symptoms. Low
      alkaline phosphatase levels are a signature of HPP, but reference ranges vary
      according to gender and age. Key features are defined and management strategies
      discussed, focusing on enzyme replacement therapy. Finally, a patient registry
      aimed at better defining the prevalence of HPP and raising awareness is
      described. CONCLUSIONS: HPP is a rare disease with a wide spectrum of
      manifestations, with orodental symptoms featuring prominently in the natural
      history. Dental professionals may be positioned at the beginning of the
      diagnostic pathway; thus, recognition of HPP features for timely referral and
      optimal disease management is important.

PMID- 27030891
TI  - Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision
      Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients
      with Acute Pulmonary Embolism. A Randomized Clinical Trial.
AB  - RATIONALE: Outpatient treatment of pulmonary embolism (PE) may lead to improved
      patient satisfaction and reduced healthcare costs. However, trials to assess its
      safety and the optimal method for patient selection are scarce. OBJECTIVES: To
      validate the utility and safety of selecting patients with PE for outpatient
      treatment by the Hestia criteria and to compare the safety of the Hestia criteria
      alone with the Hestia criteria combined with N-terminal pro-brain natriuretic
      peptide (NT-proBNP) testing. METHODS: We performed a randomized noninferiority
      trial in 17 Dutch hospitals. We randomized patients with PE without any of the
      Hestia criteria to direct discharge or additional NT-proBNP testing. We
      discharged the latter patients as well if NT-proBNP did not exceed 500 ng/L or
      admitted them if NT-proBNP was greater than 500 ng/L. The primary endpoint was 30
      day adverse outcome defined as PE- or bleeding-related mortality, cardiopulmonary
      resuscitation, or intensive care unit admission. The noninferiority margin for
      the primary endpoint was 3.4%. MEASUREMENTS AND MAIN RESULTS: We randomized 550
      patients. In the NT-proBNP group, 34 of 275 (12%) had elevated NT-proBNP values
      and were managed as inpatients. No patient (0 of 34) with an elevated NT-proBNP
      level treated in hospital (0%; 95% confidence interval [CI], 0-10.2%), versus no
      patient (0 of 23) with a post hoc-determined elevated NT-proBNP level from the
      direct discharge group (0%; 95% CI, 0-14.8%), experienced the primary endpoint.
      In both trial cohorts, the primary endpoint occurred in none of the 275 patients
      (0%; 95% CI, 0-1.3%) subjected to NT-proBNP testing, versus in 3 of 275 patients
      (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.25). During the 3
      month follow-up, recurrent venous thromboembolism occurred in two patients
      (0.73%; 95% CI, 0.1-2.6%) in the NT-proBNP group versus three patients (1.1%; 95%
      CI, 0.2-3.2%) in the direct discharge group (P = 0.65). CONCLUSIONS: Outpatient
      treatment of patients with PE selected on the basis of the Hestia criteria alone
      was associated with a low risk of adverse events. Given the low number of
      patients with elevated NT-proBNP levels, this trial was unable to draw definite
      conclusions regarding the incremental value of NT-proBNP testing in patients who
      fulfill the Hestia criteria. Clinical trial registered with
      www.trialregister.nl/trialreg/admin/rctview.asp?TC=2603 (NTR2603).

PMID- 27030893
TI  - Nano drug delivery systems: a new paradigm for treating metal toxicity.
AB  - INTRODUCTION: The standard medical treatment for metal toxicity is chelation
      therapy. Chelating agents work by forming less toxic complexes with the toxic
      metal ions which are readily excreted from the body. These compounds, based on
      their hydrophilic/lipophilic property, can either remove toxic metal ions from
      extracellular sites or can penetrate the intracellular compartments to facilitate
      the removal of toxic metal ions. However, there are various disadvantages
      associated with this kind of therapy, notably, selectivity. Other problems and
      challenges are that the therapy regime is expensive, time consuming and has poor
      patient compliance. Two chelating agents, dimercaptosuccinic acid (DMSA) and
      dimercaptopropionicsulfonate (DMPS) have gained increased acceptance among
      clinicians, undoubtedly improving the management of metal intoxications. AREAS
      COVERED: The present review provides an insight into the conventional chelating
      agents, new chelators under development, and the new opportunities presented by
      the use of nanotherapy for the treatment of metal poisoning cases. EXPERT
      OPINION: Today's research should not only focus towards development of alternate
      chelators but also targeted therapy such as the nanotherapy.

PMID- 27030894
TI  - Identification of in vivo and in vitro metabolites of 4,5-dimethoxycanthin-6-one
      by HPLC-Q-TOF-MS/MS.
AB  - 4,5-Dimthexycanthin-6-one and 5-hydroxy-4-methoxycanthin-6-one are the main
      active ingredients of Picrasma quassioides, which is a widely used herbal
      medicine for the treatment of gastroenteritis, snakebite, infection and
      hypertension in China. In the present study, the in vitro metabolites of 4,5
      dimethoxycanthin-6-one in rat, mouse, dog and human liver microsomes, as well as
      the in vivo metabolites in rat plasma and urine following a single oral dose of
      4,5-dimethoxycanthin-6-one, were identified by high-performance liquid
      chromatography combined with triple TOF mass spectrometry (HPLC-TOF/MS/MS). The
      metabolites were elucidated based on an accurate mass measurement, the MS/MS
      fragmentation patterns, the retention times of the parent drug and its
      metabolites, and the relevant drug biotransformation rules. After incubation in
      liver mcrosomes for 50 min, 4,5-dimethoxycanthin-6-one produced 8 phase I
      metabolites including 2 mono-demethylated metabolites (M1, M2), 3 mono
      hydroxylated metabolites (M3-M5), and 3 mono-demethylated and mono-hydroxylated
      metabolites (M6-M8) in rat and mouse liver microsomes, 7 phase I metabolites
      (without M7) in dog and human liver microsomes. After a single oral
      administration of 4,5-dimethoxycanthin-6-one to rats, there were 3 phase I
      metabolites (M1, M2 and M5) detected in rat plasma and 5 phase I metabolites (M1
      M5) in rat urine. Phase II metabolites were not detected in rat plasma and urine.
      Among these metabolites, mono-demethylated metabolites (M1 and M2) were the major
      metabolites of 4,5-dimethoxycanthin-6-one, mono-hydroxylated metabolites (M3-M5)
      were the minor metabolites of 4,5-dimethoxycanthin-6-one.

PMID- 27030895
TI  - An HPLC-MS method for the quantification of new acetylcholinesterase inhibitor PC
      48 (7-MEOTA-donepezil like compound) in rat plasma: Application to a
      pharmacokinetic study.
AB  - A simple, rapid and sensitive method based on liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) has been developed and validated for the quantitative
      determination in rat plasma of a new candidate for AD treatment, namely PC 48 (a
      7-MEOTA-donepezil like compound) in rat plasma. Sample preparation involved pH
      adjustment with sodium hydroxide followed by solvent extraction with ethyl
      acetate:dichloromethane (80:20, v/v). The chromatographic separation was achieved
      on an Ascentis Express RP-Amide column (75 mm * 2.1mm, 2.7 MUm) with a gradient
      mobile phase consisting of 0.05 M aqueous formic acid and acetonitrile. Detection
      was carried out using positive-ion electrospray tandem mass spectrometry on an
      LTQ XL system using the MS/MS CID (collision-induced dissociation) mode. The
      method was linear in the range 0.1-1000 ng/ml (r(2)=0.999) with a lower limit of
      quantitation of 0.1 ng/mL. Extraction recovery was in the range 63.5-72.1% for PC
      48 and 70.5% for reserpine (internal standard, IS). Intra- and inter-day
      precisions measured as relative standard deviation were below 10.8% and accuracy
      was from -7.2% to 7.4%. The method was successfully applied to a pharmacokinetic
      study involving intramuscular application of 3.86 mg/kg PC 48 to rats for the
      first time. Pharmacokinetic parameters for PC 48 include Cmax 39.09 +/- 4.45
      ng/mL,Tmax 5.00 +/- 3.08 min, AUC0-t 23374 +/- 4045 min ng/mL and t1/2 1065 +/-
      246 min.

PMID- 27030896
TI  - Childhood adversity and adult health: Evaluating intervening mechanisms.
AB  - Substantial evidence has accumulated supporting a causal link between childhood
      adversity and risk for poor health years and even decades later. One
      interpretation of this evidence is that this linkage arises largely or
      exclusively from a process of biological embedding that is not modifiable by
      subsequent social context or experience - implying childhood as perhaps the only
      point at which intervention efforts are likely to be effective. This paper
      considers the extent to which this long-term association arises from intervening
      differences in social context and/or environmental experiences - a finding that
      would suggest that post-childhood prevention efforts may also be effective. Based
      on the argument that the selected research definition of adult health status may
      have implications for the early adversity-adult health linkage, we use a
      representative community sample of black and white adults (N = 1252) to evaluate
      this relationship across three health indices: doctor diagnosed illnesses, self
      rated health, and allostatic load. Results generally indicate that observed
      relationships between childhood adversity and dimensions of adult health status
      were totally or almost totally accounted for by variations in adult socioeconomic
      position (SEP) and adult stress exposure. One exception is the childhood SEP
      allostatic load association, for which a statistically significant relationship
      remained in the context of adult stress and SEP. This lone finding supports a
      conclusion that the impact of childhood adversity is not always redeemable by
      subsequent experience. However, in general, analyses suggest the likely utility
      of interventions beyond childhood aimed at reducing exposure to social stress and
      improving social and economic standing. Whatever the effects on adult health that
      derive from biological embedding, they appear to be primarily indirect effects
      through adult social context and exposure. 

PMID- 27030898
TI  - Relationships following Neurological Conditions.

PMID- 27030897
TI  - Long-term transportation noise annoyance is associated with subsequent lower
      levels of physical activity.
AB  - Noise annoyance (NA) might lead to behavioral patterns not captured by noise
      levels, which could reduce physical activity (PA) either directly or through
      impaired sleep and constitute a noise pathway towards cardiometabolic diseases.
      We investigated the association of long-term transportation NA and its main
      sources (aircraft, road, and railway) at home with PA levels. We assessed 3842
      participants (aged 37-81) that attended the three examinations (SAP 1, 2, and 3
      in years 1991, 2001 and 2011, respectively) of the population-based Swiss cohort
      on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Participants
      reported general 24-h transportation NA (in all examinations) and source-specific
      NA at night (only SAP 3) on an ICBEN-type 11-point scale. We assessed moderate,
      vigorous, and total PA from a short-questionnaire (SAP 3). The main outcome was
      moderate PA (active/inactive: cut-off>=150min/week). We used logistic regression
      including random effects by area and adjusting for age, sex, socioeconomic
      status, and lifestyles (main model) and evaluated potential effect modifiers. We
      analyzed associations with PA at SAP 3 a) cross-sectionally: for source-specific
      and transportation NA in the last year (SAP 3), and b) longitudinally: for 10-y
      transportation NA (mean of SAP 1+2), adjusting for prior PA (SAP 2) and changes
      in NA (SAP 3-2). Reported NA (score>=5) was 16.4%, 7.5%, 3%, and 1.1% for 1-year
      transportation, road, aircraft, and railway at SAP 3, respectively. NA was
      greater in the past, reaching 28.5% for 10-y transportation NA (SAP 1+2). The 10
      y transportation NA was associated with a 3.2% (95% CI: 6%-0.2%) decrease in
      moderate PA per 1-NA rating point and was related to road and aircraft NA at
      night in cross-sectional analyses. The longitudinal association was stronger for
      women, reported daytime sleepiness or chronic diseases and it was not explained
      by objectively modeled levels of road traffic noise at SAP 3. In conclusion, long
      term NA (related to psychological noise appraisal) reduced PA and could represent
      another noise pathway towards cardiometabolic diseases. 

PMID- 27030899
TI  - Systemic psychotherapy with families where someone has an autism spectrum
      condition.
AB  - BACKGROUND: Families play an important role in facilitating the development and
      well-being of children with autism spectrum conditions. OBJECTIVES: After setting
      the scene with a clinical example, and providing a brief discussion of the
      current thinking about the aetiology of Autism spectrum conditions, this paper
      provides a review of the literature regarding the practice of systemic
      psychotherapy with families in which a child has an autism spectrum condition
      (ASC). METHODS: A search of databases and journals revealed a large number of
      opinion papers regarding how family therapists might work with families of
      children with ASCs and a smaller number of papers that describe or explore actual
      clinical practice. RESULTS: Pilot studies using qualitative methods and practice
      based evidence in the form of descriptions of clinical work offer a solid footing
      on which to develop systemic practice to help families where a person has an ASC.
      CONCLUSION: Given the multifactorial nature of the aetiology of ASCs it is
      suggested that systemic interventions have the potential to influence changes at
      multiple levels of functioning for the child and the family.

PMID- 27030900
TI  - Brain injury family intervention for adolescents: A solution-focused approach.
AB  - BACKGROUND: Strengths-based approaches are increasingly utilized in health care,
      but little is known about their practical application in rehabilitation with
      families after pediatric acquired brain injury (ABI). OBJECTIVE: To describe a
      strengths-based model, Solution-Focused Brief Therapy (SFBT) and its clinical
      application to family intervention for adolescents with ABI. METHODS: A
      literature review highlights a growing movement towards resilience and strengths
      based approaches to family intervention after pediatric ABI. The authors
      introduce the assumptions, tenets, and clinical application of SFBT, which is a
      competency-based and resource-based model that focuses on family strengths and
      successes. A direct comparison is made between the traditional medical model and
      the solution-focused paradigm. RESULTS: Key elements of SFBT are described,
      including specific strategies, techniques, and its clinical application in the
      Brain Injury Family Intervention for Adolescents (BIFI-A). The BIFI-A, designed
      for adolescents with ABI and their families, is a 12-session manualized
      intervention that encompasses education about ABI, skill building, and emotional
      support. CONCLUSIONS: Given the increased interest for research regarding
      strengths-based approaches in pediatric rehabilitation, the utilization of SFBT
      with families of adolescents with ABI warrants further attention and
      investigation. The BIFI-A, with its underpinnings of SFBT, is a promising new
      family system intervention that also merits further research.

PMID- 27030901
TI  - The effectiveness of social communication partner training for adults with severe
      chronic TBI and their families using a measure of perceived communication
      ability.
AB  - BACKGROUND: Training for communication partners of people with traumatic brain
      injury (TBI) is efficacious when using blinded independent ratings of casual
      conversations measured in the clinic. However, the question remains as to whether
      participants with TBI and their significant other perceive changes to everyday
      social communication as a result of training. OBJECTIVE: To determine whether
      treatment focused on improving the conversational skills of everyday
      communication partners of people with severe TBI using a program called TBI
      Express resulted in improvements in perceived communicative ability as measured
      by the La Trobe Communication Questionnaire (LCQ). METHODS: Non randomized
      controlled trial comparing treatment of people with TBI together with
      communication partners (JOINT) with treatment of people with TBI without partner
      involvement (TBI SOLO) and a waitlist control group (CTRL) with follow-up at 6
      months post-treatment. Forty-four outpatients from brain injury units in Sydney
      with severe chronic acquired brain injuries were recruited. A further 27 eligible
      outpatients refused to participate or could not be contacted. A total of 41
      people completed treatment and 38 completed 6 month follow up assessment. The
      measure of perceived communication ability is the report of the participant with
      TBI and their partner on the LCQ. RESULTS: Communication partner training (JOINT)
      improved conversational performance relative to training the person with TBI
      alone and a waitlist control group on the LCQ. The TBI SOLO group improved in
      terms of report on the LCQ relative to the CONTROL group. Results were maintained
      at six months post-training. CONCLUSION: Training communication partners of
      people with chronic severe TBI using TBI Express led to perceived improvements in
      everyday communication ability by both the person with TBI and their family
      member.

PMID- 27030902
TI  - Helping families thrive in the face of uncertainty: Strengths based approaches to
      working with families affected by progressive neurological illness.
AB  - BACKGROUND: Management of the uncertainty inherent in a diagnosis of a
      progressive neurological illness is one of the major adjustment tasks facing
      those affected and their families. A causal relationship has been demonstrated
      between perceived illness uncertainty and negative psychological outcomes for
      individuals with progressive neurological illness. Whilst there is a small and
      promising intervention literature on the use of a range of individually focused
      strengths based psychological interventions there appears to be little guidance
      available how clinicians might help those family members of those affected.
      OBJECTIVE: To undertake a systematic review of the evidence on the use of
      strengths based, family focused interventions that target illness uncertainty.
      METHODS: A systematic literature search was undertaken using the National Library
      for Health abstract database. RESULTS: Five papers were included in the review,
      only two of which were published in peer reviewed journals. All five reported on
      strengths based approaches that could be used with families but only two
      explicitly identified illness uncertainty as a target. Outcome measures were
      heterogeneous so data could not be aggregated for meta-analysis. The results
      suggested that these interventions showed promised but the review highlighted a
      number of methodological issues which mean that the results must be interpreted
      with caution. CONCLUSIONS: There is very little evidence of the use of strengths
      based approaches to helping families manage the uncertainty associated with
      progressive neurological illness despite it having been identified as a key
      target for intervention. The review highlights the need for the development of an
      intervention framework to address this key clinical issue and suggests one model
      that might show promise.

PMID- 27030903
TI  - Marital instability after brain injury: An exploratory analysis.
AB  - BACKGROUND: Spousal caregivers have an important role in recovery after brain
      injury, and there is evidence that injury has an adverse impact on uninjured
      partners as well as survivors. Unfortunately, the impact of brain injury on
      coupled relationships has received limited attention from clinical researchers.
      OBJECTIVE: To characterize marital stability after traumatic brain injury
      considering the perspectives of the patient and the uninjured partner. To
      identify predictors of marital stability. METHODS: Forty-two couples with mild to
      severe injury completed the Marital Status Inventory, a measure of relationship
      stability, and the Revised Dyadic Adjustment Scale (RDAS), a measure of
      relationship quality. RESULTS: Twenty-four percent (24%) of patients viewed their
      marriage as unstable as did 29% of partners. Most individuals (72%) agreed with
      their partner regarding the stability of their relationship. About half of
      patients (52%) and partners (50%) reported clinically significant levels of
      marital dissatisfaction. Multivariate logistic regression indicated that the RDAS
      was a salient predictor of marital stability. Findings indicate relatively high
      levels of marital stability despite high levels of marital distress. CONCLUSIONS:
      Marital stability can be classified beyond labeling couples as married,
      separated, or divorced. Researchers have suggested that postinjury marital
      relationships are prone to instability and divorce in comparison to the general
      population. The present findings suggest otherwise.

PMID- 27030904
TI  - Treating male sexual dysfunction after traumatic brain injury: Two case reports.
AB  - BACKGROUND: Sexual dysfunction is common after traumatic brain injury (TBI) but
      evaluation of treatment interventions have been sparse. OBJECTIVE: To report on
      the treatment of sexual dysfunction for two males with severe TBI. METHODS AND
      RESULTS: Case one was treated for erectile dysfunction (ED). After a medical
      examination which found no underlying physiological problems, Sildenafil was
      prescribed. Scores on the Golombok Rust Inventory of Sexual Satisfaction
      Impotence subscale found that scores had improved from the dysfunction range at
      baseline to the functional range at 6 weeks follow-up. There was some reduction
      in this improvement at 3 months follow-up, maybe associated with a co-morbid
      deterioration of emotional state. Case two was treated for idiopathic delayed
      ejaculation (DE). A standard sex therapy intervention was employed that resulted
      in the resolution of the problem, documented on the Sex Behavior sub-scale of the
      Derogatis Inventory for Sexual Functioning-Self Report (comparing baseline to
      post intervention and follow-up scores). CONCLUSIONS: The case reports show
      promise for the treatment of sexual dysfunction after severe TBI using standard
      medical and sex therapy treatments. In the future, controlled evaluations are
      required to demonstrate the efficacy of such interventions.

PMID- 27030905
TI  - Friendships and intimacy: Promoting the maintenance and development of
      relationships in residential neurorehabilitation.
AB  - BACKGROUND: Social re-integration after acquired brain injury is an important
      part of successful rehabilitation outcome, both in terms of return to work and
      emotional wellbeing. Residential rehabilitation often places individuals at a
      distance from their pre injury social context. Supporting the maintenance or
      development of intimate relationships is therefore a crucial aspect of
      neurobehavioural rehabilitation. However, the development of new relationships is
      not without risk. OBJECTIVE: To provide a framework for considering interventions
      around personal and intimate relationships post brain injury, taking into account
      the complexities of risk assessment and risk management. METHOD: The authors have
      used clinical case examples to develop a framework to support risk assessment and
      intervention planning. The framework has been used in a residential
      rehabilitation service to support the development and maintenance of intimate
      relationships post injury. No formal data collection was used. RESULTS: Case
      examples are used to illustrate how the framework can assist clinical practice.
      CONCLUSIONS: The authors provide a framework to assist clinicians working with
      complex clinical cases to think through options for intervention to maintain or
      develop friendships and intimacy whilst taking account of factors affecting risk
      management.

PMID- 27030906
TI  - Social cognition and executive functioning predictors of supervisors' appraisal
      of interpersonal behaviour in the workplace following acquired brain injury.
AB  - BACKGROUND: Social cognition and executive functioning difficulties following
      acquired brain injury have been linked to negative employment outcomes, such as
      demotion and loss of vocational roles. These are very counter-intuitive and
      challenging difficulties for other employees and work supervisors who have little
      or no brain injury knowledge, whose perceptions of play a key role in their
      responses to these difficulties and the final outcome of such problems for
      vocational status. OBJECTIVES: This study aimed to study the relationship between
      social cognition and executive functioning difficulties and the perceptions of
      work supervisors' appraisal of survivor interpersonal behaviour and social skills
      in the workplace. METHOD: The performance of 73 survivors of acquired brain
      injury (47% TBI, 38% CVA, 15% other ABI type; 73% male; mean age 45.44 years,
      range 19-64 years; mean time since injury 6.36 years, range 10.5-31.33 years),
      currently in a vocational rehabilitation placement) on neuropsychological tests
      of executive functioning and social cognition was measured. Informant ratings on
      the Social Skills Factor subscale from the Work Personality Profile (WPP, Bolton
      & Roessler, 1986) were used as the primary outcome measure, a vocational
      functioning questionnaire assessing social and presentational aspects of
      workplace behaviour. The raters were non-clinical workplace informants acting in
      a supervisory role (supervisory placement providers and job coaches). RESULTS:
      Correlational analysis identified significant associations between the WPP and
      survivor goal-orientated planning and implementation, mentalising ability,
      recognition of positive and negative emotions, and recognition of simple sarcasm
      (all significant at p <  0.05). These correlates were entered into a stepwise
      multiple regression. The combination final of survivor mentalising ability and
      executive functioning explained 32 % of the variance in the WPP ratings (F (2,
      52) =  12.15, p <  0.001). CONCLUSION: Certain limitations of the study
      withstanding, the current findings add to previous literature in highlighting the
      relevance of survivor executive functioning and social cognition difficulties for
      the perceptions and appraisal of work colleagues, consistent with other studies
      that have identified negative vocational outcomes associated with such
      neuropsychological difficulties. The implications for vocational rehabilitation
      are discussed.

PMID- 27030907
TI  - Momentum: A smartphone application to support shared decision making for people
      using mental health services.
AB  - OBJECTIVE: The aim of the pilot study was to examine the use of a smartphone
      application as a modern decision aid to support shared decision making in mental
      health. METHOD: 78 people using mental health services and 116 of their providers
      participated in a 4-month pilot study. At the end of the intervention, we
      conducted 3 focus group interviews with 12 multidisciplinary staff members, 1
      focus group interview with doctors, and 7 individual interviews with consumers.
      Each interview was recorded and systematically reviewed to identify common themes
      and both similar and different traits between respondents through a process of
      induction. RESULTS: Consumers and providers found the application a useful tool
      to support people in recovery in providing an overview and setting an agenda.
      However, the pilot study found more technological obstacles to its use. Some
      results indicate an obstacle perhaps relating to the power asymmetry between
      people using mental health services and staff. Contrary to our hypothesis that
      peer support would be crucial, the use of the application was most widespread
      when it was presented to consumers by providers who found it was a useful tool.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The results indicate the relevance of
      using modern technology to support shared decision making (SDM) and the recovery
      model, though raise the question of how the actual use in the study is to be
      understood. The study thereby points to a need of further research into the
      understanding of the central consumer-provider relationship in SDM and in how
      decision aids are presented. (PsycINFO Database Record

PMID- 27030908
TI  - Employer perceptions of the employability of workers in a social business.
AB  - OBJECTIVE: This study examined employer perceptions of employability of job
      candidates working in a social business for people with mental illnesses. METHOD:
      Using an analogue research design, 99 employers participated in a simulated job
      hiring process, rating 2 applicants on potential to do the job, fit with
      workplace culture and likelihood of hiring. One job applicant worked in a social
      business, and the second was either (a) working in a conventional business, (b)
      with employment lapse attributable to mental health issues, or (c) with an
      unexplained employment lapse. Paired samples t tests were used to compare
      ratings. Qualitative data were collected regarding the rationale for rankings and
      a content analysis was conducted. RESULTS: Employer rankings were significantly
      higher for the applicant working in a social business compared to either
      applicant with an employment lapse. Employers rated the candidate working in a
      conventional business significantly higher compared with the candidate in a
      social business only on ratings of likelihood to hire. Employers valued the
      recency of work experience in the social business, citing concerns about risks
      associated with employment lapses. Their comments suggested a lack of
      understanding of the nature of social business. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Experience in a social business appears to lessen the disadvantage of
      unemployment in the job hiring process, but does not appear to be ranked on par
      with experience in the conventional workforce. The social business sector could
      benefit from considering ways to publically portray these work opportunities to
      enhance acceptance and inclusion. (PsycINFO Database Record

PMID- 27030909
TI  - Mental illness sexual stigma: Implications for health and recovery.
AB  - OBJECTIVE: The majority of people in psychiatric care worldwide are sexually
      active, and studies have revealed sharply elevated rates of HIV infection in that
      group compared with the general population. Recovery-oriented treatment does not
      routinely address sexuality. We examined the relationship between gender, severe
      mental illness diagnosis, and stigma experiences related to sexuality among
      people in psychiatric outpatient care. METHOD: Sexually active adults attending 8
      public outpatient psychiatric clinics in Rio de Janeiro (N = 641) were
      interviewed for psychiatric diagnosis and stigma experiences. Stigma mechanisms
      well-established in the literature but not previously examined in relation to
      sexuality were measured with the Mental Illness Sex Stigma Questionnaire, a 27
      item interview about stigma in sexual situations and activities. RESULTS:
      Experiences of stigma were reported by a majority of participants for 48% of
      questionnaire items. Most people reported supportive attitudes toward their
      sexuality from providers and family members. Those with severe mental illness
      diagnoses showed greater stigma on individual discrimination and structural
      stigma mechanisms than did those with nonsevere mental illness diagnoses, whereas
      there was no difference on the social psychological processes (internalized
      stigma) mechanism. Regardless of diagnosis or gender, a majority of participants
      devalued themselves as sexual partners. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Adults in psychiatric outpatient care frequently reported stigma
      experiences related to aspects of their sexual lives. From the perspectives of
      both HIV prevention and recovery from mental illness, examinations of the
      consequences of stigma in the sexual lives of people in psychiatric care and
      improving their measurement would have wide applicability. (PsycINFO Database
      Record

PMID- 27030910
TI  - Notes from the Field: Imported Cases of Malaria--Puerto Rico, July-October 2015.
AB  - On July 16 2015, the Puerto Rico Department of Health (PRDH) was notified of a
      case of malaria, diagnosed by a hospital parasitology laboratory in a student who
      had traveled to Punta Cana, Dominican Republic, during late June for a school
      organized graduation trip. Malaria is a mosquito-borne parasitic infection,
      characterized by fever, shaking chills, headaches, muscle pains, nausea, general
      malaise, and vomiting (1). Malaria can be clinically difficult to distinguish
      from other acute febrile illnesses, and a definitive diagnosis requires
      demonstration of malaria parasites using microscopy or molecular diagnostic
      tests. The student's initial diagnosis on July 10 was suspected dengue virus
      infection. Puerto Rico eliminated local malaria transmission during the mid-1950s
      (2); however, reintroduction remains a risk because of the presence of a
      competent vector (Anopheles albimanus) and ease of travel to areas where the
      disease is endemic, including Hispaniola, the island shared by the Dominican
      Republic and Haiti, and the only island in the Caribbean with endemic malaria
      (3). During 2014, the Dominican Republic reported 496 confirmed malaria cases and
      four associated deaths; Haiti reported 17,662 confirmed cases and nine deaths
      (4). During 2000-2014, Puerto Rico reported a total of 35 imported malaria cases
      (range = 0-7 per year); three cases were imported from Hispaniola. During June
      August 2015, eight confirmed malaria cases among travelers to the Dominican
      Republic were reported to CDC's National Malaria Surveillance System (CDC,
      unpublished data, 2015). 

PMID- 27030911
TI  - Birefringence-Directed Raman Selection Rules in 2D Black Phosphorus Crystals.
AB  - The incident and scattered light engaged in the Raman scattering process of low
      symmetry crystals always suffer from the birefringence-induced depolarization.
      Therefore, for anisotropic crystals, the classical Raman selection rules should
      be corrected by taking the birefringence effect into consideration. The
      appearance of the 2D anisotropic materials provides an excellent platform to
      explore the birefringence-directed Raman selection rules, due to its controllable
      thickness at the nanoscale that greatly simplifies the situation comparing with
      bulk materials. Herein, a theoretical and experimental investigation on the
      birefringence-directed Raman selection rules in the anisotropic black phosphorus
      (BP) crystals is presented. The abnormal angle-dependent polarized Raman
      scattering of the Ag modes in thin BP crystal, which deviates from the normal
      Raman selection rules, is successfully interpreted by the theoretical model based
      on birefringence. It is further confirmed by the examination of different Raman
      modes using different laser lines and BP samples of different thicknesses.

PMID- 27030912
TI  - Regulation of nuclear shape and size in plants.
AB  - Nuclear shape and size changes have long been used by cytopathologists to
      diagnose, stage, and prognose cancer. However, the underlying causalities and
      molecular mechanisms are largely unknown. The current eukaryotic tree of life
      groups eukaryotes into five supergroups, with all organisms between humans and
      yeast falling into the supergroup Opisthokonta. The emergence of model organisms
      with strong molecular genetic methodology in the other supergroups has recently
      facilitated a broader evolutionary approach to pressing biological questions.
      Here, we review what is known about the control of nuclear shape and size in the
      Archaeplastidae, the supergroup containing the higher plants. We discuss common
      themes as well as differences toward a more generalized model of how eukaryotic
      organisms regulate nuclear morphology.

PMID- 27030913
TI  - Validate or falsify: Lessons learned from a microscopy method claimed to be
      useful for detecting Borrelia and Babesia organisms in human blood.
AB  - BACKGROUND: A modified microscopy protocol (the LM-method) was used to
      demonstrate what was interpreted as Borrelia spirochetes and later also Babesia
      sp., in peripheral blood from patients. The method gained much publicity, but was
      not validated prior to publication, which became the purpose of this study using
      appropriate scientific methodology, including a control group. METHODS: Blood
      from 21 patients previously interpreted as positive for Borrelia and/or Babesia
      infection by the LM-method and 41 healthy controls without known history of tick
      bite were collected, blinded and analysed for these pathogens by microscopy in
      two laboratories by the LM-method and conventional method, respectively, by PCR
      methods in five laboratories and by serology in one laboratory. RESULTS:
      Microscopy by the LM-method identified structures claimed to be Borrelia- and/or
      Babesia in 66% of the blood samples of the patient group and in 85% in the
      healthy control group. Microscopy by the conventional method for Babesia only did
      not identify Babesia in any samples. PCR analysis detected Borrelia DNA in one
      sample of the patient group and in eight samples of the control group; whereas
      Babesia DNA was not detected in any of the blood samples using molecular methods.
      CONCLUSIONS: The structures interpreted as Borrelia and Babesia by the LM-method
      could not be verified by PCR. The method was, thus, falsified. This study
      underlines the importance of doing proper test validation before new or modified
      assays are introduced.

PMID- 27030914
TI  - Microscopy of human blood for Borrelia burgdorferi and Babesia without clinical
      or scientific rationale.

PMID- 27030915
TI  - Healthcare workers mobile phone usage: A potential risk for viral contamination.
      Surveillance pilot study.
AB  - BACKGROUND: Mobile phones are commonly used by healthcare workers (HCW) in the
      working environment, as they allow instant communication and endless resource
      utilisation. Studies suggest that mobile phones have been implicated as
      reservoirs of bacterial pathogens, with the potential to cause nosocomial
      infection. This study aimed to investigate the presence of Respiratory Syncytial
      Virus, Adenovirus and Influenza Virus on HCWs mobile phones and to identify risk
      factors implied by HCWs practice of mobile phones in a clinical paediatric
      environment. METHODS: Fifty HCWs' mobile phones were swabbed over both sides of
      the mobile phone, for testing of viral contamination during 8 days in January
      2015. During the same period, a questionnaire investigating usage of mobile
      phones was given to 101 HCWs. RESULTS: Ten per cent of sampled phones were
      contaminated with viral pathogens tested for. A total of 91% of sampled
      individuals by questionnaire used their mobile phone within the workplace, where
      37% used their phone at least every hour. Eighty-nine (88%) responders were aware
      that mobile phones could be a source of contamination, yet only 13 (13%)
      disinfect their cell phone regularly. CONCLUSION: Mobile phones in clinical
      practice may be contaminated with viral pathogenic viruses. HCWs use their mobile
      phone regularly while working and, although the majority are aware of
      contamination, they do not disinfect their phones.

PMID- 27030916
TI  - Humoral response to influenza vaccination in relation to pre-vaccination antibody
      titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio.
AB  - BACKGROUND: Annual vaccination against influenza virus is generally recommended
      to elderly and chronically ill, but the relative importance of factors
      influencing the outcome is not fully understood. METHODS: In this study of 88
      individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI)
      antibodies to trivalent inactivated influenza vaccine was correlated with HI
      titres before vaccination, prior vaccinations against influenza, cytomegalovirus
      serostatus and, as an estimate of immune risk profile, the ratio between CD4 +
      and CD8 + T cells. RESULTS: Vaccine responses were impaired by high pre-existing
      HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8
      ratio had a negative impact on the vaccine response. Cytomegalovirus
      seropositivity had no apparent effect on HI titres before or after vaccination.
      CONCLUSIONS: It is concluded that both pre-existing HI antibodies and previous
      vaccinations to influenza may influence the humoral response to influenza
      vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to
      respond to repeated antigenic stimulation.

PMID- 27030917
TI  - Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy
      and reduces the overall use of antimicrobial agents during induction therapy for
      acute leukaemia: A single-centre study.
AB  - BACKGROUND: Due to an outbreak of extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli and Klebsiella pneumoniae, the routine use of
      fluoroquinolone prophylaxis was questioned. As a result, this study was conducted
      with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of
      broad-spectrum antibioctics and anti-mycotics. METHODS: A cohort of 139
      consecutive patients with acute leukaemia treated with remission-inducing
      induction chemotherapy between 2004-2012 at the Department of Haematology in
      Uppsala University Hospital was analysed. RESULTS: Fifty-three patients (38%)
      received broad-spectrum antibiotics at the initiation of chemotherapy and were
      not eligible for prophylaxis. Of the remaining patients, the initiation of broad
      spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin
      prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The
      median duration of systemic antibiotic treatment was 6 days shorter in patients
      receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the
      cumulative (total) median days on systemic antibiotic treatment was shortened by
      8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02),
      carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were
      used significantly less often when ciprofloxacin prophylaxis was given.
      CONCLUSIONS: Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and
      reduced overall antibiotic use in this study. These benefits must be evaluated vs
      the risks of development of resistant bacterial strains, making fluoroquinolone
      prophylaxis an open question for debate.

PMID- 27030918
TI  - Prosthetic joint infections secondary to rapidly growing mycobacteria: Two case
      reports and a review of the literature.
AB  - Rapidly growing mycobacteria (RGM) are a rare but treatable cause of prosthetic
      joint infections. This study reports on two patients comprising three prosthetic
      joint infections caused by RGM successfully treated at the institution. With
      removal of the infected prosthetic joint and judicious use of prolonged courses
      of antibiotics, patients with prosthetic joint infections secondary to RGM can
      both be cured and retain function of the affected joint. In addition, this study
      identified 40 additional cases reported during an extensive review of the
      literature and provide a summary of these cases. These infections can present
      within days of arthroplasty or can develop only decades after the index surgery.
      The clinical presentations often mimic those of more routine bacterial prosthetic
      joint infections. 

PMID- 27030920
TI  - Human infection with a highly pathogenic avian influenza A (H5N6) virus in Yunnan
      province, China.
AB  - Highly pathogenic avian influenza A H5N6 virus has caused four human infections
      in China. This study reports the preliminary findings of the first known human
      case of H5N6 in Yunnan province. The patient initially developed symptoms of sore
      throat and coughing on 27 January 2015. The disease rapidly progressed to severe
      pneumonia, multiple organ dysfunctions and acute respiratory distress syndrome
      and the patient died on 6 February. Virological analysis determined that the
      virus belonged to H5 clade 2.3.4.4 and it has obtained partial ability for
      mammalian adaptation and amantadine resistance. Environmental investigation found
      H5 in 63% of the samples including poultry faeces, tissues, cage surface swabs
      and sewage from local live poultry markets by real-time RT-PCR. These findings
      suggest that the expanding and enhancing of surveillance in both avian and humans
      are necessary to monitor the evolution of H5 influenza virus and to facilitate
      early detection of suspected cases. 

PMID- 27030919
TI  - Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly
      virulent Escherichia coli.
AB  - Neonatal meningitis is a rare but devastating condition. Multi-drug resistant
      (MDR) bacteria represent a substantial global health risk. This study reports on
      an aggressive case of lethal neonatal meningitis due to a MDR Escherichia coli
      (serotype O75:H5:K1). Serotyping, MDR pattern and phylogenetic typing revealed
      that this strain is an emergent and highly virulent neonatal meningitis E. coli
      isolate. The isolate was resistant to both ampicillin and gentamicin; antibiotics
      currently used for empiric neonatal sepsis treatment. The strain was also
      positive for multiple virulence genes including K1 capsule, fimbrial adhesion
      fimH, siderophore receptors iroN, fyuA and iutA, secreted autotransporter toxin
      sat, membrane associated proteases ompA and ompT, type II polysaccharide
      synthesis genes (kpsMTII) and pathogenicity-associated island (PAI)-associated
      malX gene. The presence of highly-virulent MDR organisms isolated in neonates
      underscores the need to implement rapid drug resistance diagnostic methods and
      should prompt consideration of alternate empiric therapy in neonates with Gram
      negative meningitis. 

PMID- 27030921
TI  - Comparison of performance of two Treponema pallidum automated chemiluminescent
      immunoassays in blood donors.
AB  - The recrudescence of syphilis is leading to the development of new serological
      tests. The goal of this study was to compare the performance of the more recent
      Elecsys Syphilis assay, the Electro Chemiluminescence Immunoassay (ECLIA), with
      the former Architect Syphilis TP assay, the Chemiluminescent Microparticle
      Immunoassay (CMIA), for the detection of antibodies against Treponema pallidum in
      blood donors. Serum samples of 5543 voluntary blood donors were screened in
      parallel with two tests. All repeatedly reactive (RR) samples by one or both
      assays were further analysed for confirmation by immmunoblot INNO-LIA and TPHA.
      Of 32 RR samples by CMIA, 21 were confirmed positive; of 21 RR samples by ECLIA,
      20 were confirmed positive. The sensitivities of CMIA and ECLIA were 100% and
      95.24% (95% CI = 85.71-100), respectively, not significant (p > 0.05). The
      specificity and predictive positive value (PPV) of CMIA were 99.86% (95% CI =
      99.74-99.94) and 72.41%, respectively, while the specificity and PPV of ECLIA
      were both 100%, being statistically significant (p = 0.01 for both). The overall
      agreement was 99.80% and the Cohen's kappa coefficients was 0.79. In conclusion,
      the recent Elecsys Syphilis assay could represent another reliable assay for
      blood donor screening. 

PMID- 27030922
TI  - Ischemia modified albumin in early neonatal sepsis.

PMID- 27030923
TI  - Adsorption Properties of MFM-400 and MFM-401 with CO2 and Hydrocarbons:
      Selectivity Derived from Directed Supramolecular Interactions.
AB  - ([Sc2(OH)2(BPTC)]) (H4BPTC = biphenyl-3,3',5,5'-tetracarboxylic acid), MFM-400
      (MFM = Manchester Framework Material, previously designated NOTT), and
      ([Sc(OH)(TDA)]) (H2TDA = thiophene-2,5-dicarboxylic acid), MFM-401, both show
      selective and reversible capture of CO2. In particular, MFM-400 exhibits a
      reasonably high CO2 uptake at low pressures and competitive CO2/N2 selectivity
      coupled to a moderate isosteric heat of adsorption (Qst) for CO2 (29.5 kJ mol(
      1)) at zero coverage, thus affording a facile uptake-release process. Grand
      canonical Monte Carlo (GCMC) and density functional theory (DFT) computational
      analyses of CO2 uptake in both materials confirmed preferential adsorption sites
      consistent with the higher CO2 uptake observed experimentally for MFM-400 over
      MFM-401 at low pressures. For MFM-400, the Sc-OH group participates in moderate
      interactions with CO2 (Qst = 33.5 kJ mol(-1)), and these are complemented by weak
      hydrogen-bonding interactions (O...H-C = 3.10-3.22 A) from four surrounding
      aromatic -CH groups. In the case of MFM-401, adsorption is provided by
      cooperative interactions of CO2 with the Sc-OH group and one C-H group. The
      binding energies obtained by DFT analysis for the adsorption sites for both
      materials correlate well with the observed moderate isosteric heats of adsorption
      for CO2. GCMC simulations for both materials confirmed higher uptake of EtOH
      compared with nonpolar vapors of toluene and cyclohexane. This is in good
      correlation with the experimental data, and DFT analysis confirmed the formation
      of a strong hydrogen bond between EtOH and the hydrogen atom of the hydroxyl
      group of the MFM-400 and MFM-401 framework (FW) with H-OEtOH...H-OFW distances of
      1.77 and 1.75 A, respectively. In addition, the accessible regeneration of MFM
      400 and MFM-401 and release of CO2 potentially provide minimal economic and
      environmental penalties. 

PMID- 27030925
TI  - The DoD Global, Laboratory-based, Influenza Surveillance Program: summary for the
      2013-2014 influenza season.
AB  - This report for the 2013-2014 influenza season summarizes the results of
      influenza surveillance carried out by the DoD Global, Laboratory-based, Influenza
      Surveillance Program, which is managed by the U.S. Air Force School of Aerospace
      Medicine Epidemiology Consult Service and Epidemiology Laboratory at Wright
      Patterson Air Force Base, OH. Sentinel sites submitted 3,903 specimens for
      clinical diagnostic testing and 1,163 (29.8%) were positive for influenza virus.
      The predominant influenza subtype was influenza A(H1N1)pdm09, identified in 79.2%
      of all influenza-positive specimens. The other most common subtypes were
      influenza A(H3N2) (10.5%) and influenza B (10.1%). In August 2014, a human case
      of influenza A(H3N2) variant was identified in a patient with a history of
      exposure to swine. Adjusted vaccine effectiveness (VE) was calculated among 1,016
      military dependents and retirees in the U.S. and was found to be 44.8% for all
      vaccine types. Uncertainties and other limitations associated with estimating VE
      are discussed. 

PMID- 27030924
TI  - Assessment of treatment response in tuberculosis.
AB  - Antibiotic treatment of tuberculosis has a duration of several months. There is
      significant variability of the host immune response and the pharmacokinetic
      pharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the
      site of disease. A limitation of sputum-based measures of treatment response may
      be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub
      populations. Potential biomarkers and surrogate endpoints should be benchmarked
      against hard clinical outcomes (failure/relapse/death) and may need tailoring to
      specific patient populations. Here, we assess the evidence supporting currently
      utilized and future potential host and pathogen-based models and biomarkers for
      monitoring treatment response in active and latent tuberculosis. Biomarkers for
      monitoring treatment response in extrapulmonary, pediatric and drug resistant
      tuberculosis are research priorities.

PMID- 27030926
TI  - Correlation between antimicrobial resistance in Escherichia coli infections in
      hospitalized patients and rates of inpatient prescriptions for selected
      antimicrobial agents, Department of Defense hospitals, 2010-2014.
AB  - During the past decade, increasing prevalence of antimicrobial resistance in
      Escherichia coli has complicated treatment of infections. Several studies have
      shown significant correlations between levels of susceptibility and levels of
      prescription use for preferred antimicrobials; however, most of these studies
      were conducted outside the U.S. and are outdated. This analysis aimed to identify
      inpatient E. coli infection trends and correlations between prescriptions and
      antimicrobial resistance observed among hospitalized Department of Defense
      beneficiaries during 2010-2014. A descending trend was observed for E. coli
      infection incidence during 2010-2013, with an upward trend noted for the last
      year of the study. Despite quarterly fluctuations, descending trends were noted
      among prescription rates and stable trends were observed for resistance rates
      throughout the study period. A statistically significant moderate and positive
      correlation (r=0.53; p=0.01) was noted between levels of ciprofloxacin
      prescriptions and ciprofloxacin resistance for E. coli isolates. Stewardship
      programs are encouraged to monitor this relationship. 

PMID- 27030927
TI  - The epidemiology of herpes simplex virus type 2 infections in a large cohort of
      HIV-infected patients, 2006-2014.

PMID- 27030928
TI  - Update: Heat injuries, active component, U.S. Army, Navy, Air Force, and Marine
      Corps, 2015.
AB  - The incidence rate of heat stroke among active component members of the U.S.
      Army, Navy, Air Force, and Marine Corps in 2015 was higher than rates in the
      previous 4 years. Incidence rates of heat stroke were higher among males, those
      younger than 20 years of age, Asian/Pacific Islanders, Marine Corps and Army
      members, and service members in combat-specific occupations, compared to their
      respective counterparts. More service members were treated for "other heat
      injuries" in 2015 (n=1,933) than in either of the previous 2 years. The incidence
      rate of "other heat injuries" was higher among females than males and rates were
      highest among service members younger than 20 years of age, among Army and Marine
      Corps members, among recruit trainees, and among service members in combat
      specific occupations. During 2011-2015, 720 diagnoses of heat injuries were
      documented among service members serving in Iraq/Afghanistan; 6.9% (n=50) of
      those diagnoses were for heat stroke. 

PMID- 27030929
TI  - Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force,
      and Marine Corps, 2011-2015.
AB  - Among active component members of the U.S. Army, Navy, Air Force, and Marine
      Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to
      physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of
      incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and
      2015. In 2015, the highest incidence rates occurred in service members who were
      male; younger than 20 years of age; black, non-Hispanic; members of the Marine
      Corps and Army; recruit trainees; and in combat-specific occupations. Most cases
      of exertional rhabdomyolysis were diagnosed at installations that support basic
      combat/recruit training or major ground combat units of the Army or Marine Corps.
      Medical care providers should consider exertional rhabdomyolysis in the
      differential diagnosis when service members (particularly recruits) present with
      muscular pain and swelling, limited range of motion, or the excretion of dark
      urine (e.g., myoglobinuria) after strenuous physical activity, particularly in
      hot, humid weather. 

PMID- 27030930
TI  - Update: Exertional hyponatremia, active component, U.S. Army, Navy, Air Force,
      and Marine Corps, 2000-2015.
AB  - From 2000 through 2015, there were 1,542 incident diagnoses of exertional
      hyponatremia among active component members of the U.S. Army, Navy, Air Force,
      and Marine Corps. Annual incidence rates rose sharply from 2008 through 2010 but
      then decreased by more than 50% from 2010 through 2013. In 2015, the number of
      cases (n=116) increased by approximately 20% from the previous year. The recent
      increase in rates overall reflects increased rates in the Army and the Marine
      Corps. Relative to their respective counterparts, crude incidence rates of
      exertional hyponatremia for the entire 16-year surveillance period were higher
      among females, those in the youngest age group, Marines, and recruit trainees.
      Service members (particularly recruit trainees) and their supervisors must be
      vigilant for early signs of heat-related illnesses and must be knowledgeable of
      the dangers of excessive water consumption and the prescribed limits for water
      intake during prolonged physical activity (e.g., field training exercises,
      personal fitness training, recreational activities) in hot, humid weather. 

PMID- 27030931
TI  - Functional lumen imaging probe: The FLIP side of esophageal disease.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize use of the functional
      lumen imaging probe (FLIP) for the evaluation and management of esophageal
      diseases. RECENT FINDINGS: The FLIP utilizes high-resolution impedance planimetry
      to evaluate the functional geometry and cross-sectional area/pressure
      relationship (i.e. distensibility) of the esophageal sphincters and body. Recent
      studies have reported the potential utility of FLIP to evaluate esophageal
      diseases, such as achalasia, gastroesophageal reflux disease, and eosinophilic
      esophagitis. SUMMARY: Esophageal distensibility measures provided by the FLIP
      will add to our understanding of the contribution of esophageal mechanical
      properties to esophageal symptoms and function. Application of the FLIP in
      clinical practice complements the diagnostic evaluation of esophageal function
      and may also be a valuable tool to help direct and target clinical management of
      esophageal diseases.

PMID- 27030932
TI  - Functional Outcomes and Physical Impairments in Pediatric Critical Care
      Survivors: A Scoping Review.
AB  - OBJECTIVE: Although more children are surviving critical illness, little is known
      about long-term physical impairment. This scoping review aims to critically
      appraise existing literature on functional outcome measurement tools, prevalence,
      and risk factors for physical impairments in pediatric critical care survivors.
      DATA SOURCES: PubMed, Embase, and Cumulative Index to Nursing and Allied Health
      Literature, using a combination of MeSH terms and keywords (critical illness,
      intensive care, and functional outcomes/status). STUDY SELECTION: All human
      studies reporting functional outcomes in children 0-18 years old admitted to the
      PICU. Non-English language, adult and preterm infant studies were excluded. DATA
      SYNTHESIS: Three global assessment tools and eight multidimensional measures were
      used to measure functional outcome in pediatric survivors of critical illness.
      Rates of acquired functional impairment in a general pediatric intensive care
      cohort ranged from 10% to 36% at discharge and 10% to 13% after more than 2
      years. Risk factors for acquired functional impairment include illness severity,
      the presence of organ dysfunction, length of ICU stay, and younger age. There is
      some evidence that physical impairment may be more severe and persistent than
      psychosocial components. CONCLUSIONS: Functional impairment may be persistent in
      pediatric survivors of critical care. Unfortunately, studies varied largely in
      measurement timing and tools used. The lack of differentiation between impairment
      in different functional domains limited the generalizability of data. Further
      studies using a combination of standardized measures at various time points of
      the disease process can help establish more comprehensive rates of physical
      impairment.

PMID- 27030934
TI  - Photoisomerization of Vibrationally Hot Tetramethylethylene Produced by Ultrafast
      Internal Conversion from the Excited State.
AB  - Isomerization of tetramethylethylene (TME) following ultrafast internal
      conversion was investigated using time-resolved photoelectron spectroscopy with
      vacuum-ultraviolet probe pulses. The difference photoelectron spectrum at tau =
      15 ps was reasonably well reproduced using a linear combination of static
      photoelectron spectra of TME and its isomers. The isomers were produced as a
      consequence of unimolecular reaction of vibrationally hot TME, created by
      internal conversion from the excited state. 

PMID- 27030933
TI  - Species-level persistence probabilities for recovery and conservation status
      assessment.
AB  - Recovery planning for species listed under the U.S. Endangered Species Act has
      been hampered by a lack of consistency and transparency, which can be improved by
      implementing a standardized approach for evaluating species status and developing
      measurable recovery criteria. However, managers lack an assessment method that
      integrates threat abatement and can be used when demographic data are limited. To
      help meet these needs, we demonstrated an approach for evaluating species status
      based on habitat configuration data. We applied 3 established persistence
      measures (patch occupancy, metapopulation capacity, and proportion of population
      lost) to compare 2 conservation strategies (critical habitat designated by the
      U.S. Fish and Wildlife Service and the Forest Service's Carbonate Habitat
      Management Strategy) and 2 threat scenarios (maximum limestone mining, removal of
      all habitat in areas with mining claims; minimum mining, removal of habitat only
      in areas with existing operations and high-quality ore) against a baseline of
      existing habitat for 3 federally listed plant species. Protecting all area within
      the designated critical habitat maintained a similar level (83.9-99.9%) of
      species persistence as the baseline, whereas maximum mining greatly reduced
      persistence (0.51-38.4% maintained). The 3 persistence measures provided
      complementary insights reflecting different aspects of habitat availability
      (total area, number of patches, patch size, and connectivity). These measures can
      be used to link recovery criteria developed following the 3 R principles
      (representation, redundancy, and resilience) to the resulting improvements in
      species viability. By focusing on amount and distribution of habitat, our method
      provides a means of assessing the status of data-poor species to inform decision
      making under the Endangered Species Act.

PMID- 27030935
TI  - Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of
      diabetes mellitus and pancreatic cancer.
AB  - Increasing evidence suggests that vitamin D exerts multiple effects beyond bone
      and calcium metabolism. Vitamin D seems to play a role in pancreatic disease,
      including type 1 and type 2 diabetes mellitus as well as pancreatic cancer.
      Vitamin D's immune-modulatory action suggests that it could help prevent type 1
      diabetes. In type 2 diabetes, vitamin D may influence beta-cell function, insulin
      sensitivity, and systematic inflammation-all characteristic pathways of that
      disease. Data from observational studies correlated vitamin D deficiency with
      risk of type 1 and type 2 diabetes. Prospective and ecological studies of
      pancreatic cancer incidence generally support a beneficial effect of higher 25
      hydroxyvitamin D concentration as well as inverse correlations between UVB dose
      or exposure and incidence and/or mortality rate of pancreatic cancer. This review
      discusses the literature regarding vitamin D's role in risk of diabetes and
      pancreatic cancer. The results to date generally satisfy Hill's criteria for
      causality regarding vitamin D and incidence of these pancreatic diseases.
      However, large randomized, blinded, prospective studies are required to more
      fully evaluate the potential therapeutic role of vitamin D in preventing
      pancreatic diseases.

PMID- 27030936
TI  - Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks.
AB  - Graphene offers promising advantages for biomedical applications. However,
      adoption of graphene technology in biomedicine also poses important challenges in
      terms of understanding cell responses, cellular uptake, or the intracellular fate
      of soluble graphene derivatives. In the biological microenvironment, graphene
      nanosheets might interact with exposed cellular and subcellular structures,
      resulting in unexpected regulation of sophisticated biological signaling. More
      broadly, biomedical devices based on the design of these 2D planar nanostructures
      for interventions in the central nervous system require an accurate understanding
      of their interactions with the neuronal milieu. Here, we describe the ability of
      graphene oxide nanosheets to down-regulate neuronal signaling without affecting
      cell viability.

PMID- 27030937
TI  - Comparison of ACL strain estimated via a data-driven model with in vitro
      measurements.
AB  - Computer modeling and simulation techniques have been increasingly used to
      investigate anterior cruciate ligament (ACL) loading during dynamic activities in
      an attempt to improve our understanding of injury mechanisms and development of
      injury prevention programs. However, the accuracy of many of these models remains
      unknown and thus the purpose of this study was to compare estimates of ACL strain
      from a previously developed three-dimensional, data-driven model with those
      obtained via in vitro measurements. ACL strain was measured as the knee was
      cycled from approximately 10 degrees  to 120 degrees  of flexion at 20 deg s(-1)
      with static loads of 100, 50, and 50 N applied to the quadriceps, biceps femoris
      and medial hamstrings (semimembranosus and semitendinosus) tendons, respectively.
      A two segment, five-degree-of-freedom musculoskeletal knee model was then scaled
      to match the cadaver's anthropometry and in silico ACL strains were then
      determined based on the knee joint kinematics and moments of force. Maximum and
      minimum ACL strains estimated in silico were within 0.2 and 0.42% of that
      measured in vitro, respectively. Additionally, the model estimated ACL strain
      with a bias (mean difference) of -0.03% and dynamic accuracy (rms error) of 0.36%
      across the flexion-extension cycle. These preliminary results suggest that the
      proposed model was capable of estimating ACL strains during a simple flexion
      extension cycle. Future studies should validate the model under more dynamic
      conditions with variable muscle loading. This model could then be used to
      estimate ACL strains during dynamic sporting activities where ACL injuries are
      more common. 

PMID- 27030938
TI  - Selective Androgen Receptor Modulators as Function Promoting Therapies.

PMID- 27030939
TI  - Use of Biomarkers.
AB  - Expanding the concept of frailty to the clinical settings has raised the concern
      about the accuracy of the current definitions for identifying frail individuals
      (not populations). The usual tools to assess frailty show, among other
      characteristics, a low sensitivity and a low Positive Predictive Value. One
      approach to overcome this challenge is using biological biomarkers to improve
      those characteristics, making feasible and accurate the assessment of frailty in
      clinical settings. Many biomarkers of frailty have been identified but few of
      them have been assessed as clinical markers with controversial results. Taking
      into account that frailty is caused by the failure in different systems, it is
      worthy to check if the combination of several of these biomarkers could be of
      help. In this effort, the EU-funded project FRAILOMIC is trying to assess the
      ability of different sets of biomarkers for improving the accuracy of classical
      definitions in determining the risk, the diagnosis and the prognosis of frailty. 

PMID- 27030940
TI  - Frailty and Sarcopaenia Trials in Primary Care - Identifying and Overcoming Key
      Barriers to Successful Clinician Participation.
AB  - Primary care research involving older people brings together a wide range of
      primary care practitioners. Key areas of activity include: health promotion,
      disease prevention, screening and early diagnosis, as well as the management of
      common and long-term conditions such as frailty and sarcopaenia which are under
      researched domains of health in this setting. Few interventional studies have
      identified frail or sarcopaenic patients as the target population based on recent
      definitions of either condition. Several barriers to successful research in the
      primary care area exist and overcoming such barriers is not straightforward but
      involves a multidimensional approach that attempts to enhance the confidence and
      opportunity to engage in research of primary care staff and the consideration of
      factors that allow external leads of research to coordinate their programme. 

PMID- 27030941
TI  - Co-Presence of Multimorbidity and Disability with Frailty: An Examination of
      Heterogeneity in the Frail Older Population.
AB  - BACKGROUND: Frailty is often associated with multimorbidity and disability.
      OBJECTIVES: We investigated heterogeneity in the frail older population by
      characterizing five subpopulations according to quantitative biological markers,
      multimorbidity and disability, and examined their association with mortality and
      nursing home admission. DESIGN: Observational study. PARTICIPANTS: Participants
      (n=4,414) were from the population-based Age Gene/Environment Susceptibility
      Reykjavik Study. MEASUREMENTS: Frailty was defined by >= 3 of five
      characteristics: weight loss, weakness, reduced energy levels, slowness and
      physical inactivity. Multimorbidity was assessed using a simple disease count,
      based on 13 prevalent conditions. Disability was assessed by five activities of
      daily living; participants who had difficulty with one or more tasks were
      considered disabled. Differences among frail subpopulations were based on the co
      presence of multimorbidity and disability. Differences among the following
      subpopulations were examined: 1) Non-frail (reference group); 2) Frail only; 3)
      Frail with disability; 4) Frailty with multimorbidity; 5) Frail with disability
      and multimorbidity. RESULTS: Frailty was present in 10.7% (n=473). Frailty was
      associated with increased risk for mortality (OR 1.40; 95% CI 1.15-1.69) and
      nursing home admission (OR 1.50; 95% CI 1.16-1.93); risks differed by
      subpopulations. Compared to the non-frail, the frail only group had poorer
      cognition and increased inflammation levels but did not have increased risk for
      mortality (OR 1.40; 95% CI 0.84-2.33) or nursing home admission (OR 1.01; 95% CI
      0.46-2.21). Compared to the non-frail, the other frail subpopulations had
      significantly poorer cognition, increased inflammation levels, more white matter
      lesions, higher levels of calcium, glucose and red cell distribution width and
      increased risk for mortality and nursing home admission. CONCLUSIONS: The adverse
      health risks associated with frailty in the general older adult population may
      primarily be driven by increased disease burden and disability.

PMID- 27030942
TI  - Frailty and Pain: Two Related Conditions.
AB  - Frailty is a multidimensional syndrome, involving functional, nutritional,
      biological and psychological aspects. This condition, defined as a decreased
      resistance to internal and external stressors, is predictive of adverse health
      outcomes, including disability and mortality. Importantly, the frailty syndrome
      is usually considered a reversible condition, thus amenable of specific
      preventive interventions. Persistent pain in older adults is very common and has
      multiple determinants. This symptom represents a determinant of accelerated
      aging. In the present paper, we discuss available evidence examining the
      association between these two conditions. Despite the high prevalence of these
      two conditions and their shared underlying mechanisms, our search only retrieved
      few relevant studies. Most of them reported a relationship between pain (or
      analgesics consumption) and different operational definitions of frailty. Pain
      may represent a relevant risk factor as well as a potential target for
      interventions against the frailty syndrome, but further studies are needed. 

PMID- 27030943
TI  - Components of the Risk Instrument for Screening in the Community (RISC) that
      Correlate with Public Health Nurses' Perception of Risk.
AB  - BACKGROUND: Functional decline and frailty are common in community-dwelling older
      adults, leading to an increased risk of adverse outcomes. OBJECTIVE: To examine
      the factors that public health nurses perceive to cause risk of three adverse
      outcomes: institutionalisation, hospitalisation, and death, in older adults,
      using the Risk Instrument for Screening in the Community (RISC). DESIGN: A
      quantitative, correlational, descriptive design was used. SETTING AND
      PARTICIPANTS: A sample of 803 community-dwellers, aged over 65 years receiving
      regular follow-up by public health nurses. Procedure and Measurements: Public
      health nurses (n=15) scored the RISC and the Clinical Frailty Scale (CFS) on
      patients in their caseload. We examined and compared correlations between the
      severity of concern and ability of the caregiver network to manage these concerns
      with public health nurses' perception of risk of the three defined adverse
      outcomes. RESULTS: In total, 782 RISC scores were available. Concern was higher
      for the medical state domain (686/782,88%) compared with the mental state
      (306/782,39%) and activities of daily living (595/782,76%) domains. Concern was
      rated as severe for only a small percentage of patients. Perceived risk of
      institutionalisation had the strongest correlation with concern over patients
      mental state,(r=0.53), while risk of hospitalisation,(r=0.53) and death,(r=0.40)
      correlated most strongly with concern over the medical state. Weaker correlations
      were found for the other domains and RISC scores. The CFS most strongly
      correlated with the ADL domain,(r=0.78). CONCLUSION: Although the prevalence of
      concern was high, it was mostly rated as mild. Perceived risk of
      institutionalisation correlated most with concern over the ability of caregiver
      networks to manage patients' mental state, while risk of hospitalisation and
      death correlated with patients' medical state. The findings suggest the
      importance of including an assessment of the caregiver network when examining
      community-dwelling older adults. Validation of the RISC and public health nurses'
      ratings are now required.

PMID- 27030944
TI  - Effects of Caloric Restriction with or without Resistance Training in Dynapenic
      Overweight and Obese Menopausal Women: A MONET Study.
AB  - OBJECTIVE: The dynapenic (DYN)-obese phenotype is associated with an impaired
      metabolic profile. However, there is a lack of evidences regarding the effect of
      lifestyle interventions on the metabolic profile of individual with dynapenic
      phenotype. The objective was to investigate the impact of caloric restriction
      (CR) with or without resistance training (RT) on body composition, metabolic
      profile and muscle strength in DYN and non-dynapenic (NDYN) overweight and obese
      menopausal women. DESIGN: 109 obese menopausal women (age 57.9 +/- 9.0 yrs; BMI
      32.1 +/- 4.6 kg/m2) were randomized to a 6-month CR intervention with or without
      a RT program. Participants were categorized as DYN or NDYN based on the lowest
      tertile of relative muscle strength in our cohort (< 4.86 kg/BMI). MEASUREMENTS:
      Body composition was measured by DXA, body fat distribution by CT scan, glucose
      homeostasis at fasting state and during an euglycemic-hyperinsulinemic clamp,
      fasting lipids, resting blood pressure, fasting inflammation markers and maximal
      muscle strength. RESULTS: No difference was observed between groups at baseline
      for body composition and the metabolic profile. Overall, a treatment effect was
      observed for all variables of body composition and some variables of the
      metabolic profile (fasting insulin, glucose disposal, triglyceride levels,
      triglycerides/HDL-Chol ratio and resting diastolic blood pressure) (P between
      0.05 and 0.001). No Group X Treatment interaction was observed for variables of
      body composition and the metabolic profile. However, an interaction was observed
      for muscle strength; which significantly improved more in the CR+RT NDYN group
      (all P <= 0.05). CONCLUSIONS: In the present study, dynapenia was not associated
      with a worse metabolic profile at baseline in overweight and obese menopausal
      women. DYN and NDYN menopausal women showed similar cardiometabolic benefit from
      CR or CR+RT interventions. However, our results showed that the addition of RT to
      CR was more effective in improving maximal strength in DYN and NDYN obese
      menopausal women.

PMID- 27030946
TI  - Abstracts from Women's Health 2016: The 24(th) Annual Congress April 14-17, 2016
      Washington, DC.

PMID- 27030945
TI  - Alterations in coagulation following major liver resection.
AB  - The international normalised ratio is frequently raised in patients who have
      undergone major liver resection, and is assumed to represent a potential bleeding
      risk. However, these patients have an increased risk of venous thromboembolic
      events, despite conventional coagulation tests indicating hypocoagulability. This
      prospective, observational study of patients undergoing major hepatic resection
      analysed the serial changes in coagulation in the early postoperative period.
      Thrombin generation parameters and viscoelastic tests of coagulation
      (thromboelastometry) remained within normal ranges throughout the study period.
      Levels of the procoagulant factors II, V, VII and X initially fell, but V and X
      returned to or exceeded normal range by postoperative day five. Levels of factor
      VIII and Von Willebrand factor were significantly elevated from postoperative day
      one (p < 0.01). Levels of the anticoagulants, protein C and antithrombin remained
      significantly depressed on postoperative day five (p = 0.01). Overall, the
      imbalance between pro- and anticoagulant factors suggested a prothrombotic
      environment in the early postoperative period.

PMID- 27030947
TI  - Microbiological Cutoff Values: A Critical Issue in Phenotypic Antibiotic
      Resistance Assessment of Lactobacilli and Bifidobacteria.
AB  - The purpose of this study was to assess the antimicrobial resistance profiles of
      several strains of Lactobacillus and Bifidobacterium spp. of probiotic interest.
      The International Organization for Standardization method was used to determine
      the minimal inhibitory concentrations of the antibiotics recommended by the
      European Food Safety Authority (EFSA). As a result, some of the tested
      microorganisms showed a visible growth up to the microbiological cutoff values
      indicated by EFSA guidelines in 2012. We were not able to categorize these
      strains as susceptible or resistant on the basis of antimicrobial resistance
      phenotypic testing as EFSA document does not explicitly deal with such a
      phenotypic condition where strains grow at antibiotic concentrations up to the
      established cutoff value. Although a few strains have been analyzed for this
      study, our findings highlight a potential challenge in accurately determining the
      antibiotic resistance in specific strains relevant for human and animal health.

PMID- 27030948
TI  - Seventh Report on the Standardisation of Terminology of Lower Urinary Tract
      Function: Lower Urinary Tract Rehabilitation Techniques.

PMID- 27030949
TI  - Long-Term PEG-J Tube Safety in Patients With Advanced Parkinson's Disease.
AB  - OBJECTIVES: The objectives of this study were to present procedure- and device
      associated adverse events (AEs) identified with long-term drug delivery via
      percutaneous endoscopic gastrojejunostomy (PEG-J). Levodopa-carbidopa intestinal
      gel (LCIG, also known in US as carbidopa-levodopa enteral suspension, CLES) is
      continuously infused directly to the proximal small intestine via PEG-J in
      patients with advanced Parkinson's disease (PD) to overcome slow and erratic
      gastric emptying and treat motor fluctuations that are not adequately controlled
      by oral or other pharmacological therapy. METHODS: An independent adjudication
      committee of three experienced (>25 years each) gastroenterologists reviewed
      gastrointestinal procedure- and device-associated AEs reported for PD patients
      (total n=395) enrolled in phase 3 LCIG studies. The rate, clinical significance,
      and causality of the procedure/device events were determined. RESULTS: The
      patient median exposure to PEG-J at the data cutoff was 480 days. Procedure- and
      device-associated serious AEs (SAEs) occurred in 67 (17%) patients. A total of
      42% of SAEs occurred during the first 4 weeks following PEG-J placement. SAEs of
      major clinical significance with the highest procedural incidence were
      peritonitis (1.5%), pneumonia (1.5%), and abdominal pain (1.3%). The most common
      non-serious procedure- and device-associated AEs were abdominal pain (31%), post
      operative wound infection (20%), and procedural pain (23%). In all, 17 (4.3%)
      patients discontinued treatment owing to an AE. CONCLUSIONS: In conclusion,
      incidences of PEG-J AEs with the LCIG delivery system and PEG-J longevity were
      compared favorably with ranges described in the PEG/PEG-J literature. A low
      discontinuation rate in this study suggests acceptable procedural outcomes and AE
      rates in PD patients treated with this PEG-J drug delivery system.

PMID- 27030950
TI  - Harnessing the Power of Posttranscriptional Gene Silencing in Crohn's Disease.

PMID- 27030952
TI  - Autotrophic growth and lipid production of Chlorella sorokiniana in lab batch and
      BIOCOIL photobioreactors: Experiments and modeling.
AB  - A novel mathematical model for the quantitative assessment of the effect of
      dissolved nitrogen on the autotrophic batch-growth and lipid accumulation of
      Chlorella sorokiniana, is proposed in this work. Model results have been
      validated through comparison with suitable experimental data performed in lab
      photobioreactors. Further experiments have been then performed using the BIOCOIL
      photobioreactor operated in fed-batch mode. The experimental results, which show
      that a maximum growth rate of 0.52day(-1) and a lipid content equal to 25%wt can
      be achieved with the BIOICOIL, have been successfully predicted through the
      proposed model. Therefore, the model might represent a first step toward the
      development of a tool for the scale-up and optimization of the operating
      conditions of BIOCOIL photobioreactors. Finally, the fatty acid methyl esters
      obtained by trans-esterification of lipids extracted from C. sorokiniana, have
      been analyzed in view of the assessment of their usability for producing
      biodiesel. 

PMID- 27030951
TI  - Population-Based Breast Cancer Screening With Risk-Based and Universal
      Mammography Screening Compared With Clinical Breast Examination: A Propensity
      Score Analysis of 1 429 890 Taiwanese Women.
AB  - IMPORTANCE: Different screening strategies for breast cancer are available but
      have not been researched in quantitative detail. OBJECTIVE: To assess the
      benefits and the harms of risk-based and universal mammography screening in
      comparison with annual clinical breast examination (CBE). DESIGN: Population
      based cohort study comparing incidences of stage II+ disease and death from
      breast cancer across 3 breast cancer screening strategies, with adjustment for a
      propensity score for participation based on risk factors for breast cancer and
      comparing the 3 strategies for overdetection between January 1999 and December
      2009. Asymptomatic women attending outreach screening in the community or
      undergoing mammography in hospitals were enrolled in the 3 screening programs.
      INTERVENTIONS: Risk-based biennial mammography, universal biennial mammography,
      and annual CBE. MAIN OUTCOMES AND MEASURES: Detection rates, stage II+ disease
      incidence, mortality from breast cancer, and overdiagnosis were compared using a
      time-dependent Cox proportional hazards regression model. RESULTS: A total of 1
      429 890 asymptomatic women attending outreach screening in the community or
      undergoing mammography in hospitals were enrolled in the 3 screening programs.
      Detection rates (prevalent screen and subsequent screens per 1000) were the
      highest for universal biennial mammography (4.86 and 2.98, respectively),
      followed by risk-based mammography (2.80 and 2.77, respectively), and lowest for
      annual CBE (0.97 and 0.70, respectively). Universal biennial mammography
      screening, compared with annual CBE, was associated with a 41% mortality
      reduction (risk ratio, 0.59; 95% CI, 0.48-0.73) and a 30% reduction of stage II+
      breast cancer (RR, 0.70; 95% CI, 0.66-0.74). Risk-based mammography screening was
      associated with an 8% reduction of stage II+ breast cancer (RR, 0.92; 95% CI,
      0.86-0.99) but was not associated with a statistically significant mortality
      reduction (risk ratio [RR], 0.86; 95% CI, 0.73-1.02). Estimates of overdiagnosis
      were no different from CBE for risk-based screening and 13% higher than CBE for
      universal mammography. CONCLUSIONS AND RELEVANCE: Compared with population-based
      screening for breast cancer with annual CBE, universal biennial mammography
      resulted in a substantial reduction in breast cancer deaths, whereas risk-based
      biennial mammography resulted in only a modest benefit. Compared with annual CBE,
      risk-based and universal mammography screening did not result in significant
      overdiagnosis of breast cancer.

PMID- 27030953
TI  - Biofilm activity and sludge characteristics affected by exogenous N-acyl
      homoserine lactones in biofilm reactors.
AB  - This study verified the effect of N-acyl homoserine lactone (AHL) concentrations
      on mature biofilm systems. Three concentrations of an AHL mixture were used in
      the batch test. Introducing of 5nM AHLs significantly increased biofilm activity
      and increased sludge characteristics, which resulted in better pollutant removal
      performance, whereas exogenous 50nM and 500nM AHLs limited pollutant removal,
      especially COD and nitrogen removal. To further identify how exogenous signal
      molecular affects biofilm system nitrogen removal, analyzing of nitrifying
      bacteria through real-time polymerase chain reaction (RT-PCR) revealed that these
      additional signal molecules affect nitrifying to total bacteria ratio. In
      addition, the running state of the system was stable during 15days of operation
      without an AHL dose, which suggests that the changes in the system due to AHL are
      irreversible. 

PMID- 27030954
TI  - Numerical modelling of biophysicochemical effects on multispecies reactive
      transport in porous media involving Pseudomonas putida for potential microbial
      enhanced oil recovery application.
AB  - pH and resident time of injected slug plays a critical role in characterizing the
      reservoir for potential microbial enhanced oil recovery (MEOR) application. To
      investigate MEOR processes, a multispecies (microbes-nutrients) reactive
      transport model in porous media was developed by coupling kinetic and transport
      model. The present work differs from earlier works by explicitly determining
      parametric values required for kinetic model by experimental investigations using
      Pseudomonas putida at different pH conditions and subsequently performing
      sensitivity analysis of pH, resident time and water saturation on concentrations
      of microbes, nutrients and biosurfactant within reservoir. The results suggest
      that nutrient utilization and biosurfactant production are found to be maximum at
      pH 8 and 7.5 respectively. It is also found that the sucrose and biosurfactant
      concentrations are highly sensitive to pH rather than reservoir microbial
      concentration, while at larger resident time and water saturation, the microbial
      and nutrient concentrations were lesser due to enhanced dispersion. 

PMID- 27030955
TI  - Catalytic production of biofuels (butene oligomers) and biochemicals
      (tetrahydrofurfuryl alcohol) from corn stover.
AB  - A strategy is presented that produces liquid hydrocarbon fuels (butene oligomers
      (BO)) from cellulose (C6) fraction and commodity chemicals (tetrahydrofurfuryl
      alcohol (THFA)) from hemicellulose (C5) of corn stover based on catalytic
      conversion technologies using 2-sec-butylphenol (SBP) solvents. This strategy
      integrates the conversion subsystems based on experimental studies and separation
      subsystems for recovery of biomass derivatives and SBP solvents. Moreover, a heat
      exchanger network is designed to reduce total heating requirements to the lowest
      level, which is satisfied from combustion of biomass residues (lignin and
      humins). Based on the strategy, this work offers two possible process designs
      (design A: generating electricity internally vs. design B: purchasing electricity
      externally), and performs an economic feasibility study for both the designs
      based on a comparison of the minimum selling price (MSP) of THFA. This strategy
      with the design B leads to a better MSP of $1.93 per kg THFA. 

PMID- 27030956
TI  - Influence of limiting factors on biomass and lipid productivities of axenic
      Chlorella vulgaris in photobioreactor under chemostat cultivation.
AB  - The understanding of process parameters and limiting conditions on microalgal
      biomass and lipid productivities is scarce especially in chemostat cultivation.
      In this study, the factors limiting growth of axenic Chlorella vulgaris OW-01 in
      cylindrical photobioreactor under chemostat cultivation were overcome in two
      phases. Physiological and physicochemical analyses determined inorganic carbon,
      phosphorous and light intensity as major limiting factors. Their effect on system
      productivity was ascertained and optimized in the first phase resulting in
      maximum biomass and lipid productivities of 538 and 128 (mg/L/d), respectively.
      In the second phase, the effect of dilution rate was evaluated under optimized
      conditions. The biomass and lipid productivities in this phase reached to 1013
      and 270 (mg/L/d), respectively at a dilution rate of 0.75d(-1), yielding >10-fold
      cumulative increase in productivities. The study demonstrates addressing resource
      limitations by constant monitoring and optimization of chemostat cultivation to
      achieve high biomass and lipid productivities in photobioreactors. 

PMID- 27030957
TI  - Adaptive evolution of Schizochytrium sp. by continuous high oxygen stimulations
      to enhance docosahexaenoic acid synthesis.
AB  - Adaptive laboratory evolution (ALE) is an effective method in changing the strain
      characteristics. Here, ALE with high oxygen as a selection pressure was applied
      to improve the production capacity of Schizochytrium sp. Results showed that cell
      dry weight (CDW) of endpoint strain was 32.4% higher than that of starting
      strain. But slight lipid accumulation impairment was observed. These major
      performance changes were accompanied with enhanced isocitrate dehydrogenase
      enzyme activity and reduced ATP:citrate lyase enzyme activity. And a serious
      decrease of 62.6% in SDHA 140rpm->170rpm was observed in the endpoint strain. To
      further study the docosahexaenoic acid (DHA) production ability of evolved
      strain, fed-batch strategy was applied and 84.34g/L of cell dry weight and
      26.40g/L of DHA yield were observed. In addition, endpoint strain produced
      greatly less squalene than starting strain. This work demonstrated that ALE may
      be a promising tool in modifying microalga strains. 

PMID- 27030958
TI  - Microwave-assisted catalytic pyrolysis of lignocellulosic biomass for production
      of phenolic-rich bio-oil.
AB  - Catalytic microwave pyrolysis of peanut shell (PT) and pine sawdust (PS) using
      activated carbon (AC) and lignite char (LC) for production of phenolic-rich bio
      oil and nanotubes was investigated in this study. The effects of process
      parameters such as pyrolysis temperature and biomass/catalyst ratio on the yields
      and composition of pyrolysis products were investigated. Fast heating rates were
      achieved under microwave irradiation conditions. Gas chromatography-mass
      spectrometry (GC-MS) analysis of bio-oil showed that activated carbon
      significantly enhanced the selectivity of phenolic compounds in bio-oil. The
      highest phenolics content in the bio-oil (61.19 %(area)) was achieved at 300
      degrees C. The selectivity of phenolics in bio-oil was higher for PT sample
      compared to that of PS. The formation of nanotubes in PT biomass particles was
      observed for the first time in biomass microwave pyrolysis. 

PMID- 27030959
TI  - Activation of glycerol metabolism in Xanthomonas campestris by adaptive evolution
      to produce a high-transparency and low-viscosity xanthan gum from glycerol.
AB  - Many studies have focused on using crude glycerol from biodiesel to obtain
      valuable products, but few of these studies have focused on obtaining
      polysaccharides. A mutant strain of Xanthomonas campestris CCTCC M2015714 that
      could use glycerol to produce high-transparency and low-viscosity xanthan gum was
      obtained by adaptive evolution, and the yield of xanthan gum reached 11.0g/L. We
      found that transcriptional levels of genes related to glycerol metabolism (glpF,
      glpK, glpD, and fbp) in the mutant strain were all higher than those from the
      parent strain. Using 5g/L sucrose or glucose as starter substrate, cell growth
      time decreased from 36h to 24h and xanthan gum yield increased. Moreover, the
      mutant strain can tolerate high titer glycerol, and its activity was not affected
      by the impurities in crude glycerol. All these results proved that crude glycerol
      from biodiesel industries can be used for xanthan gum production. 

PMID- 27030960
TI  - Observation of uniform ligand environments and (31)P-(197)Au coupling in
      phosphine-terminated Au nanoparticles.
AB  - Here, we use solution and solid-state (31)P NMR to study the ligand environment
      of water soluble, phosphine-terminated gold nanoparticles. The resulting spectra
      indicate that particle-bound phosphine ligands occupy an unexpectedly
      monodisperse ligand environment. This uniformity then facilitates one of the
      first descriptions of distinct (31)P-(197)Au coupling in colloidal nanoparticles.

PMID- 27030961
TI  - Splenic marginal zone lymphoma: Prognostic factors, role of watch and wait
      policy, and other therapeutic approaches in the rituximab era.
AB  - Splenic marginal zone lymphoma (SMZL) is an indolent lymphoma in which watch and
      wait (W&W) approach as well as splenectomy and chemo-immunotherapy are usually
      recommended. The role of the different approaches in relation to risk factors was
      evaluated. One hundred patients with SMZL were retrospectively studied. Median
      age was 65 years. HCV positivity was 3.1%. The 10-year overall-survival was 95.1%
      (CI: 90-100%). Sixty-two asymptomatic, low tumour burden patients were submitted
      to W&W. A low-risk group not requiring treatment was identified. Patients
      requiring treatment received splenectomy (36), chemotherapy-alone (27) and
      rituximab +/- chemotherapy (16). In multivariate analysis, negative predictors
      for starting treatment were female-sex, splenomegaly, ECOG >= 1. Patients with
      low IIL-Score had a better 5-year TFT (24%). The median TFT of the W&W cohort was
      58.5 months; at 10 years, 17% of patients were still on W&W. Splenectomy and
      rituximab +/- chemotherapy showed similar results, while chemotherapy alone
      proved inferior. This real-life single-centre study of SMZL confirmed its very
      good prognosis with a survival likelihood overlapping that of general population.
      The prognostic role of IIL-Score was confirmed. The W&W approach allowed a median
      PFS longer than in follicular lymphoma. Finally, our data confirm the inferiority
      of chemotherapy compared to splenectomy and rituximab+/-chemotherapy.

PMID- 27030962
TI  - Evaluation of gemtuzumab ozogamycin associated sinusoidal obstructive syndrome:
      Findings from an academic pharmacovigilance program review and a pharmaceutical
      sponsored registry.
AB  - BACKGROUND: In 2000, the Food and Drug Administration (FDA) approved gemtuzumab
      ozogamycin for monotherapy for older patients with relapsed AML. A 0.9% rate of
      hepatic sinusoidal obstructive syndrome (SOS) was noted in licensing trials. In
      2001, FDA received reports of 14 GO-associated SOS cases from MD Anderson Cancer
      Center. A State of South Carolina/National Cancer Institute funded
      pharmacovigilance program and a manufacturer sponsored registry independently
      evaluated this concern. METHODS: The manufacturer's registry and the academic
      program focused on risk factors and incidence of GO-associated SOS in routine
      clinical practice and clinical trial settings, respectively. Comparisons were
      made of findings and dissemination efforts from the two studies. RESULTS:
      Retrospective analysis of clinical trials by the academic initiative identified
      99 cases of SOS among 221 GO-treated stem cell patients and 649 patients who did
      not undergo HSCTs. SOS rates were 3% when GO was administered at doses <=6
      mg/m(2) as monotherapy or with non-hepatotoxic agents; 28% when administered with
      6-thioguanine, a hepatotoxic agent; 15% when administered as monotherapy at doses
      at a dose of 9 mg/m(2), and between 15% and 40% if a stem cell transplant (SCT)
      was performed within 3 months of GO administration. Death from SOS occurred in
      33% of the cases. The manufacturer's registry prospectively evaluated 482 GO
      treated patients who received a mean dose of 7.8 mg/m(2). Overall, 41% received
      concomitant chemotherapy, 18% had undergone prior SCT, 9.1% developed SOS, and
      death from SOS occurred in 60% of the SOS cases. Findings from each initiative
      were disseminated at national conferences and in peer-reviewed manuscripts
      beginning in 2003. CONCLUSION: Retrospective review of clinical trials, case
      series, and FDA reports and prospective registries can provide important
      information on safety signals initially identified in licensing trials.

PMID- 27030963
TI  - Discovery of Potential Biomarkers with Dose- and Time-Dependence in Cisplatin
      Induced Nephrotoxicity Using Metabolomics Integrated with a Principal Component
      Based Area Calculation Strategy.
AB  - Cisplatin is a potent chemotherapeutic agent. However, its clinical usage is
      restricted by serious adverse effects, especially nephrotoxicity. For revealing
      the dose- and time-dependence of cisplatin-induced nephrotoxicity, mass
      spectrometry-based metabolomics integrated with a principal component-based area
      calculation (PCAC) strategy was proposed in the present study. Area plots based
      on the first two principal components of the principal component analysis model
      were constructed first. Then, the sums of cumulative areas under PC-T curves
      (AUCPC-T) were calculated. Finally, the fold change of AUCPC-T between
      experimental and control groups at different time points was calculated and used
      as an indicative parameter. With the PCAC approach, dose- and time-dependence of
      cisplatin-induced metabolic change was quantitatively confirmed for the first
      time. Furthermore, 27 potential biomarkers with dose- and time-dependence related
      to nephrotoxicity induced by cisplatin were screened out and tentatively
      identified. Metabolic pathways interrupted by cisplatin mainly included energy,
      amino acid, and lipid metabolism.

PMID- 27030964
TI  - Trajectories of sleepiness and insomnia symptoms in Norwegian nurses with and
      without night work and rotational work.
AB  - Numerous cross-sectional studies report high prevalence rates of sleepiness and
      insomnia in shift workers, but few longitudinal studies exist. We investigated
      trajectories of sleepiness and insomnia symptoms in a sample of Norwegian nurses
      across four measurements, spanning a total of four years (sleepiness) and five
      years (insomnia). The participants completed the Epworth Sleepiness Scale and the
      Bergen Insomnia Scale at each measurement instance. Latent growth curve models
      were used to analyse the data. Separate models examined night work (night work,
      entering and leaving night work) and rotational work (rotational work, entering
      and leaving rotational work) as predictors for trajectories of sleepiness and
      insomnia symptoms, respectively. Baseline values of sleepiness and insomnia were
      higher among rotational shift workers than among workers with fixed shifts (day
      or night). The results showed that night work throughout the period and entering
      night work during the period were not associated with different trajectories of
      sleepiness or insomnia symptoms, compared to not having night work. The same
      results were found for rotational work and entering rotational work, compared to
      not having rotational work. Leaving night work and leaving rotational work were
      associated with a decrease in sleepiness and insomnia symptoms, compared to
      staying in such work.

PMID- 27030965
TI  - Phenotypic Variation in a Family With Pseudodominant Stargardt Disease.
AB  - Importance: Stargardt disease is a phenotypically diverse macular dystrophy
      caused by the autosomal recessive inheritance of mutations in ABCA4.
      Pseudodominant transmission occurs more often than might be expected because of
      the relatively high carrier frequency of pathogenic ABCA4 variants. Genetic
      characterization of affected individuals permits a more precise understanding of
      these genotype-phenotype associations. Observations: In this case series, we
      explore the clinical courses and genotypes of a woman and her 2 daughters with
      pseudodominant transmission of Stargardt disease. The mother had choroidal
      neovascularization that was treated with bevacizumab. Both daughters exhibited
      worse vision than their mother, despite lacking choroidal neovascularization,
      because of the extent of photoreceptor and retinal pigment epithelium atrophy in
      the macula. Genetic testing confirmed pseudodominant inheritance and the presence
      of 3 ABCA4 alleles within the family. Conclusions and Relevance: These cases
      emphasize the clinical relevance of recognizing pseudodominant transmission and
      the resultant phenotypic variability. Differing degrees of visual impairment in
      these patients emphasize the need to continue refining our understanding of how
      individual ABCA4 mutations contribute to phenotype.

PMID- 27030966
TI  - Requirements of Clinical Journals for Authors' Disclosure of Financial and Non
      Financial Conflicts of Interest: A Cross Sectional Study.
AB  - IMPORTANCE: It is unclear how medical journals address authors' financial and non
      financial conflict of interest (COI). OBJECTIVE: To assess the policies of
      clinical journals for disclosure of financial and non-financial COI. METHODS:
      Cross sectional study that included both review of public documents as well as a
      simulation of a manuscript submission for the National Library of Medicine's
      "core clinical journals". The study did not involve human subjects. Investigators
      who abstracted the data, reviewed "instructions for authors" on the journal
      website and, in order to reflect the actual implementation of the COI disclosure
      policy, simulated the submission of a manuscript. Two individuals working in
      duplicate and independently to abstract information using a standardized data
      abstraction form, resolved disagreements by discussion or with the help of a
      third person. RESULTS: All but one of 117 core clinical journals had a COI
      policy. All journals required disclosure of financial COI pertaining to the
      authors and a minority (35%) asked for financial COI disclosure pertaining to the
      family members or authors' institution (29%). Over half required the disclosure
      of at least one form of non-financial COI (57%), out of which only two (3%)
      specifically referred to intellectual COI. Small minorities of journals (17% and
      24% respectively) described a potential impact of disclosed COI and of non
      disclosure of COI on the editorial process. CONCLUSION: While financial COI
      disclosure was well defined by the majority of the journals, many did not have
      clear policies on disclosure of non-financial COI, disclosure of financial COI of
      family members and institutions of the authors, and effect of disclosed COI or
      non-disclosure of COI on editorial policies.

PMID- 27030967
TI  - EGCG Inhibited Lipofuscin Formation Based on Intercepting Amyloidogenic beta
      Sheet-Rich Structure Conversion.
AB  - BACKGROUND: Lipofuscin (LF) is formed during lipid peroxidation and sugar
      glycosylation by carbonyl-amino crosslinks with biomacrolecules, and accumulates
      slowly within postmitotic cells. The environmental pollution, modern dietary
      culture and lifestyle changes have been found to be the major sources of reactive
      carbonyl compounds in vivo. Irreversible carbonyl-amino crosslinks induced by
      carbonyl stress are essentially toxiferous for aging-related functional losses in
      modern society. Results show that (-)-epigallocatechin gallate (EGCG), the main
      polyphenol in green tea, can neutralize the carbonyl-amino cross-linking reaction
      and inhibit LF formation, but the underlying mechanism is unknown. METHODS AND
      RESULTS: We explored the mechanism of the neutralization process from protein,
      cell, and animal levels using spectrofluorometry, infrared spectroscopy,
      conformation antibodies, and electron microscopy. LF demonstrated an
      amyloidogenic beta-sheet-rich with antiparallel structure, which accelerated the
      carbonyl-amino crosslinks formation and disrupted proteolysis in both PC12 cells
      and D-galactose (D-gal)-induced brain aging mice models. Additionally, EGCG
      effectively inhibited the formation of the amyloidogenic beta-sheet-rich
      structure of LF, and prevented its conversion into toxic and on-pathway
      aggregation intermediates, thereby cutting off the carbonyl-amino crosslinks.
      CONCLUSIONS: Our study indicated that the amyloidogenic beta-sheet structure of
      LF may be the core driving force for carbonyl-amino crosslinks further formation,
      which mediates the formation of amyloid fibrils from native state of
      biomacrolecules. That EGCG exhibits anti-amyloidogenic beta-sheet-rich structure
      properties to prevent the LF formation represents a novel strategy to impede the
      development of degenerative processes caused by ageing or stress-induced
      premature senescence in modern environments.

PMID- 27030968
TI  - Investigating the Proton Donor in the NO Reductase from Paracoccus denitrificans.
AB  - Variant nomenclature: the variants were made in the NorB subunit if not indicated
      by the superscript c, which are variants in the NorC subunit (e.g. E122A =
      exchange of Glu-122 in NorB for an Ala, E71cD; exchange of Glu-71 in NorC for an
      Asp). Bacterial NO reductases (NORs) are integral membrane proteins from the heme
      copper oxidase superfamily. Most heme-copper oxidases are proton-pumping enzymes
      that reduce O2 as the last step in the respiratory chain. With electrons from
      cytochrome c, NO reductase (cNOR) from Paracoccus (P.) denitrificans reduces NO
      to N2O via the following reaction: 2NO+2e-+2H+->N2O+H2O. Although this reaction
      is as exergonic as O2-reduction, cNOR does not contribute to the electrochemical
      gradient over the membrane. This means that cNOR does not pump protons and that
      the protons needed for the reaction are taken from the periplasmic side of the
      membrane (since the electrons are donated from this side). We previously showed
      that the P. denitrificans cNOR uses a single defined proton pathway with residues
      Glu-58 and Lys-54 from the NorC subunit at the entrance. Here we further
      strengthened the evidence in support of this pathway. Our further aim was to
      define the continuation of the pathway and the immediate proton donor for the
      active site. To this end, we investigated the region around the calcium-binding
      site and both propionates of heme b3 by site directed mutagenesis. Changing
      single amino acids in these areas often had severe effects on cNOR function, with
      many variants having a perturbed active site, making detailed analysis of proton
      transfer properties difficult. Our data does however indicate that the calcium
      ligation sphere and the region around the heme b3 propionates are important for
      proton transfer and presumably contain the proton donor. The possible
      evolutionary link between the area for the immediate donor in cNOR and the proton
      loading site (PLS) for pumped protons in oxygen-reducing heme-copper oxidases is
      discussed. 

PMID- 27030969
TI  - The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014.
AB  - BACKGROUND: Outbreaks of methanol poisoning occur frequently on a global basis,
      affecting poor and vulnerable populations. Knowledge regarding methanol is
      limited, likely many cases and even outbreaks go unnoticed, with patients dying
      unnecessarily. We describe findings from the first three large outbreaks of
      methanol poisoning where Medecins Sans Frontieres (MSF) responded, and evaluate
      the benefits of a possible future collaboration between local health authorities,
      a Non-Governmental Organisation and international expertise. METHODS:
      Retrospective study of three major methanol outbreaks in Libya (2013) and Kenya
      (May and July 2014). Data were collected from MSF field personnel, local health
      personnel, hospital files, and media reports. FINDINGS: In Tripoli, Libya, over
      1,000 patients were poisoned with a reported case fatality rate of 10%
      (101/1,066). In Kenya, two outbreaks resulted in approximately 341 and 126
      patients, with case fatality rates of 29% (100/341) and 21% (26/126),
      respectively. MSF launched an emergency team with international experts,
      medications and equipment, however, the outbreaks were resolving by the time of
      arrival. INTERPRETATION: Recognition of an outbreak of methanol poisoning and
      diagnosis seem to be the most challenging tasks, with significant delay from time
      of first presentations to public health warnings being issued. In spite of the
      rapid response from an emergency team, the outbreaks were nearly concluded by the
      time of arrival. A major impact on the outcome was not seen, but large
      educational trainings were conducted to increase awareness and knowledge about
      methanol poisoning. Based on this training, MSF was able to send a local
      emergency team during the second outbreak, supporting that such an approach could
      improve outcomes. Basic training, simplified treatment protocols, point-of-care
      diagnostic tools, and early support when needed, are likely the most important
      components to impact the consequences of methanol poisoning outbreaks in these
      challenging contexts.

PMID- 27030970
TI  - A Lower Proportion of Regulatory B Cells in Patients with Henoch-Schoenlein
      Purpura Nephritis.
AB  - BACKGROUND: Henoch-Schoenlein purpura is the one of most common types of systemic
      vasculitis that involves impaired renal function and Henoch-Schoenlein purpura
      nephritis (HSPN). The diagnosis of this condition is largely based on
      immunohistologic detection of immunoglobulin A1-containing immune complex in the
      glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis
      of HSPN is still largely unknown. METHODS: In this study, we enrolled 25 newly
      diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell
      subtypes were determined in venous blood using flow cytometry. The serum
      interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent
      assay. RESULTS: Compared to those in healthy controls, the numbers of CD38+CD19+,
      CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells per microliter of blood were
      significantly higher in HSPN patients. In contrast, the numbers of CD5+CD19+, IL
      10+CD19+, CD5+CD1d+CD19+, and IL-10+CD5+CD1d+CD19+ B cells per microliter of
      blood and the serum IL-10 concentration were significantly lower in HSPN
      patients. Following treatment, the numbers of CD38+CD19+ and CD86+CD19+ B cells
      per microliter of blood were significantly reduced in HSPN patients. However, the
      numbers of CD5+CD1d+CD19+, CD5+CD1d+IL-10+CD19+, and IL-10+CD19+ B cells per
      microliter of blood and the serum IL-10 concentration were significantly
      increased in HSPN patients following treatment. The estimated glomerular
      filtration rate (eGFR) was negatively correlated with the number of CD38+CD19+ B
      cells but positively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+,
      and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10
      concentration. The 24-h urinary protein concentration was positively correlated
      with the number of CD38+CD19+B cells but negatively correlated with the numbers
      of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of
      blood and the serum IL-10 concentration. CONCLUSION: Our results suggest that
      CD38+CD19+ and CD1d+CD5+CD19+ B cells (Bregs) contribute to the pathogenesis of
      HSPN.

PMID- 27030971
TI  - PI3Kgamma Is Critical for Dendritic Cell-Mediated CD8+ T Cell Priming and Viral
      Clearance during Influenza Virus Infection.
AB  - Phosphoinositide-3-kinases have been shown to be involved in influenza virus
      pathogenesis. They are targeted directly by virus proteins and are essential for
      efficient viral replication in infected lung epithelial cells. However, to date
      the role of PI3K signaling in influenza infection in vivo has not been thoroughly
      addressed. Here we show that one of the PI3K subunits, p110gamma, is in fact
      critically required for mediating the host's antiviral response. PI3Kgamma
      deficient animals exhibit a delayed viral clearance and increased morbidity
      during respiratory infection with influenza virus. We demonstrate that p110gamma
      is required for the generation and maintenance of potent antiviral CD8+ T cell
      responses through the developmental regulation of pulmonary cross-presenting
      CD103+ dendritic cells under homeostatic and inflammatory conditions. The defect
      in lung dendritic cells leads to deficient CD8+ T cell priming, which is
      associated with higher viral titers and more severe disease course during the
      infection. We thus identify PI3Kgamma as a novel key host protective factor in
      influenza virus infection and shed light on an unappreciated layer of complexity
      concerning the role of PI3K signaling in this context. 

PMID- 27030972
TI  - Characterization of the N2O-producing soil bacterium Rhizobium azooxidifex sp.
      nov.
AB  - In the context of studying the bacterial community involved in nitrogen
      transformation processes in arable soils exposed to different extents of erosion
      and sedimentation in a long-term experiment (CarboZALF), a strain was isolated
      that reduced nitrate to nitrous oxide without formation of molecular nitrogen.
      The presence of the functional gene nirK, encoding the respiratory copper
      containing nitrite reductase, and the absence of the nitrous oxide reductase gene
      nosZ indicated a truncated denitrification pathway and that this bacterium may
      contribute significantly to the formation of the important greenhouse gas N2O.
      Phylogenetic analysis based on the 16S rRNA gene sequence and the housekeeping
      genes recA and atpD demonstrated that the investigated soil isolate belongs to
      the genus Rhizobium. The closest phylogenetic neighbours were the type strains of
      Rhizobium. subbaraonis and Rhizobium. halophytocola. The close relationship with
      R. subbaraonis was reflected by similarity analysis of the recA and atpD genes
      and their amino acid positions. DNA-DNA hybridization studies revealed genetic
      differences at the species level, which were substantiated by analysis of the
      whole-cell fatty acid profile and several distinct physiological characteristics.
      Based on these results, it was concluded that the soil isolate represents a novel
      species of the genus Rhizobium, for which the name Rhizobium azooxidifex sp. nov.
      (type strain Po 20/26T=DSM 100211T=LMG 28788T) is proposed. 

PMID- 27030973
TI  - Literature Review and Comparison of Two Statistical Methods to Evaluate the
      Effect of Botulinum Toxin Treatment on Gait in Children with Cerebral Palsy.
AB  - AIM: This study aimed at comparing two statistical approaches to analyze the
      effect of Botulinum Toxin A (BTX-A) treatment on gait in children with a
      diagnosis of spastic cerebral palsy (CP), based on three-dimensional gait
      analysis (3DGA) data. Through a literature review, the available expert knowledge
      on gait changes after BTX-A treatment in children with CP is summarized. METHODS:
      Part 1--Intervention studies on BTX-A treatment in children with CP between 4-18
      years that used 3DGA data as an outcome measure and were written in English, were
      identified through a broad systematic literature search. Reported kinematic and
      kinetic gait features were extracted from the identified studies. Part 2--A
      retrospective sample of 53 children with CP (6.1 +/- 2.3years, GMFCS I-III)
      received 3DGA before and after multilevel BTX-A injections. The effect of BTX-A
      on gait was interpreted by comparing the results of paired samples t-tests on the
      kinematic gait features that were identified from literature to the results of
      statistical parametric mapping analysis on the kinematic waveforms of the lower
      limb joints. RESULTS: Part 1-53 kinematic and 33 kinetic features were described
      in literature. Overall, there is no consensus on which features should be
      evaluated after BTX-A treatment as 49 features were reported only once or twice.
      Part 2--Post-BTX-A, both statistical approaches found increased ankle
      dorsiflexion throughout the gait cycle. Statistical parametric mapping analyses
      additionally found increased knee extension during terminal stance. In turn,
      feature analyses found increased outtoeing during stance after BTX-A. CONCLUSION:
      This study confirms that BTX-A injections are a valuable treatment option to
      improve gait function in children with CP. However, different statistical
      approaches may lead to different interpretations of treatment outcome. We suggest
      that a clear, definite hypothesis should be stated a priori and a commensurate
      statistical approach should accompany this hypothesis.

PMID- 27030974
TI  - Correlates of Performance of Healthcare Workers in Emergency, Triage, Assessment
      and Treatment plus Admission Care (ETAT+) Course in Rwanda: Context Matters.
AB  - BACKGROUND: The Emergency, Triage, Assessment and Treatment plus Admission care
      (ETAT+) course, a comprehensive advanced pediatric life support course, was
      introduced in Rwanda in 2010 to facilitate the achievement of the fourth
      Millennium Development Goal. The impact of the course on improving healthcare
      workers (HCWs) knowledge and practical skills related to providing emergency care
      to severely ill newborns and children in Rwanda has not been studied. OBJECTIVE:
      To evaluate the impact of the ETAT+ course on HCWs knowledge and practical
      skills, and to identify factors associated with greater improvement in knowledge
      and skills. METHODS: We used a one group, pre-post test study using data
      collected during ETAT+ course implementation from 2010 to 2013. The paired t-test
      was used to assess the effect of ETAT+ course on knowledge improvement in
      participating HCWs. Mixed effects linear and logistic regression models were
      fitted to explore factors associated with HCWs performance in ETAT+ course
      knowledge and practical skills assessments, while accounting for clustering of
      HCWs in hospitals. RESULTS: 374 HCWs were included in the analysis. On average,
      knowledge scores improved by 22.8/100 (95% confidence interval (CI) 20.5, 25.1).
      In adjusted models, bilingual (French & English) participants had a greater
      improvement in knowledge 7.3 (95% CI 4.3, 10.2) and higher odds of passing the
      practical skills assessment (adjusted odds ratio (aOR) = 2.60; 95% CI 1.25, 5.40)
      than those who were solely proficient in French. Participants who attended a
      course outside of their health facility had higher odds of passing the skills
      assessment (aOR = 2.11; 95% CI 1.01, 4.44) than those who attended one within
      their health facility. CONCLUSIONS: The current study shows a positive impact of
      ETAT+ course on improving participants' knowledge and skills related to managing
      emergency pediatric and neonatal care conditions. The findings regarding key
      factors influencing ETAT+ course outcomes demonstrate the importance of
      considering key contextual factors (e.g., language barriers) that might affect
      HCWs performance in this type of continuous medical education.

PMID- 27030975
TI  - Cheating the Locals: Invasive Mussels Steal and Benefit from the Cooling Effect
      of Indigenous Mussels.
AB  - The indigenous South African mussel Perna perna gapes during periods of aerial
      exposure to maintain aerobic respiration. This behaviour has no effect on the
      body temperatures of isolated individuals, but when surrounded by conspecifics,
      beneficial cooling effects of gaping emerge. It is uncertain, however, whether
      the presence of the invasive mussel Mytilus galloprovincialis limits the ability
      of P. perna for collective thermoregulation. We investigated whether varying
      densities of P. perna and M. galloprovincialis influences the thermal properties
      of both natural and artificial mussel beds during periods of emersion. Using
      infrared thermography, body temperatures of P. perna within mixed artificial beds
      were shown to increase faster and reach higher temperatures than individuals in
      conspecific beds, indicating that the presence of M. galloprovincialis limits the
      group cooling effects of gaping. In contrast, body temperatures of M.
      galloprovincialis within mixed artificial mussel beds increased slower and
      exhibited lower temperatures than for individuals in beds comprised entirely of
      M. galloprovincialis. Interestingly, differences in bed temperatures and heating
      rates were largely dependent on the size of mussels, with beds comprised of
      larger individuals experiencing less thermal stress irrespective of species
      composition. The small-scale patterns of thermal stress detected within
      manipulated beds were not observed within naturally occurring mixed mussel beds.
      We propose that small-scale differences in topography, size-structure, mussel bed
      size and the presence of organisms encrusting the mussel shells mask the effects
      of gaping behaviour within natural mussel beds. Nevertheless, the results from
      our manipulative experiment indicate that the invasive species M.
      galloprovincialis steals thermal properties as well as resources from the
      indigenous mussel P. perna. This may have significant implications for predicting
      how the co-existence of these two species may change as global temperatures
      continue to rise. 

PMID- 27030976
TI  - Stable Voice Clusters Identified When Using the Maximum versus Minimum Intensity
      Curve in the Phonetogram.
AB  - OBJECTIVE: To examine whether the minimum as well as the maximum voice intensity
      (i.e. sound pressure level, SPL) curves of a voice range profile (VRP) are
      required when discovering different voice groups based on a clustering analysis.
      In this approach, no a priori labeling of voice types is used. PATIENTS AND
      METHODS: VRPs of 194 (84 male and 110 female) professional singers were
      registered and processed. Cluster analysis was performed with the use of features
      related to (1) both the maximum and minimum SPL curves and (2) the maximum SPL
      curve only. RESULTS: Features related to the maximum as well as the minimum SPL
      curves showed three clusters in both male and female voices. These clusters, or
      voice groups, are based on voice types with similar VRP features. However, when
      using features related only to the maximum SPL curve, the clusters became less
      obvious. CONCLUSION: Features related to the maximum and minimum SPL curves of a
      VRP are both needed in order to identify the three voice clusters.

PMID- 27030977
TI  - What Is Speciation?
AB  - Concepts and definitions of species have been debated by generations of
      biologists and remain controversial. Microbes pose a particular challenge because
      of their genetic diversity, asexual reproduction, and often promiscuous
      horizontal gene transfer (HGT). However, microbes also present an opportunity to
      study and understand speciation because of their rapid evolution, both in nature
      and in the lab, and small, easily sequenced genomes. Here, we review how
      microbial population genomics has enabled us to catch speciation "in the act" and
      how the results have challenged and enriched our concepts of species, with
      implications for all domains of life. We describe how recombination (including
      HGT and introgression) has shaped the genomes of nascent microbial, animal, and
      plant species and argue for a prominent role of natural selection in initiating
      and maintaining speciation. We ask how universal is the process of speciation
      across the tree of life, and what lessons can be drawn from microbes? Comparative
      genomics showing the extent of HGT in natural populations certainly jeopardizes
      the relevance of vertical descent (i.e., the species tree) in speciation.
      Nevertheless, we conclude that species do indeed exist as clusters of genetic and
      ecological similarity and that speciation is driven primarily by natural
      selection, regardless of the balance between horizontal and vertical descent. 

PMID- 27030978
TI  - Genome analysis shows Bacillus axarquiensis is not a later heterotypic synonym of
      Bacillus mojavensis; reclassification of Bacillus malacitensis and Brevibacterium
      halotolerans as heterotypic synonyms of Bacillus axarquiensis.
AB  - Bacillus axarquiensis and Bacillus malacitensis were previously reported to be
      later heterotypic synonyms of Bacillus mojavensis, based primarily on DNA-DNA
      relatedness values. We have sequenced draft genomes of Bacillus axarquiensis NRRL
      B-41617T and Bacillus malacitensis NRRL B-41618T. Comparative genomics and DNA
      DNA relatedness calculations showed that while Bacillus axarquiensis and Bacillus
      malacitensis are synonymous with each other, they are not synonymous with
      Bacillus mojavensis. In addition, a draft genome was completed for Brevibacterium
      halotolerans, a strain long suspected of being a Bacillus subtilis group member
      based on 16S rRNA similarities (99.8 % with Bacillus mojavensis). Comparative
      genomics and DNA-DNA relatedness calculations showed that Brevibacterium
      halotolerans is synonymous with Bacillus axarquiensis and Bacillus malacitensis.
      The pairwise in silico DNA-DNA hybridization values calculated in comparisons
      between the three conspecific strains were all greater than 92 %, which is well
      above the standard species threshold of 70 %. While the pairwise in silico DNA
      DNA hybridization values calculated in comparisons of the three conspecific
      strains with Bacillus mojavensis were all less than 65 %. The combined results of
      our genotype and phenotype studies showed that Bacillus axarquiensis, Bacillus
      malacitensis and Brevibacterium halotolerans are conspecific and distinct from
      Bacillus mojavensis. Because the valid publication of the name Bacillus
      axarquiensis predates the publication of the name Bacillus malacitensis, we
      propose that Bacillus malacitensis be reclassified as a synonym of Bacillus
      axarquiensis. In addition, we propose to reclassify Brevibacterium halotolerans
      as a synonym of Bacillus axarquiensis. An amended description of Bacillus
      axarquiensis is provided. 

PMID- 27030980
TI  - Genome Wide Association Study Identifies New Loci Associated with Undesired Coat
      Color Phenotypes in Saanen Goats.
AB  - This paper reports a quantitative genetics and genomic analysis of undesirable
      coat color patterns in goats. Two undesirable coat colors have routinely been
      recorded for the past 15 years in French Saanen goats. One fifth of Saanen
      females have been phenotyped "pink" (8.0%) or "pink neck" (11.5%) and
      consequently have not been included in the breeding program as elite animals.
      Heritability of the binary "pink" and "pink neck" phenotype, estimated from
      103,443 females was 0.26 for "pink" and 0.21 for "pink neck". Genome wide
      association studies (using haplotypes or single SNPs) were implemented using a
      daughter design of 810 Saanen goats sired by 9 Artificial Insemination bucks
      genotyped with the goatSNP50 chip. A highly significant signal (-log10pvalue =
      10.2) was associated with the "pink neck" phenotype on chromosome 11, suggesting
      the presence of a major gene. Highly significant signals for the "pink" phenotype
      were found on chromosomes 5 and 13 (-log10p values of 7.2 and, 7.7 respectively).
      The most significant SNP on chromosome 13 was in the ASIP gene region, well known
      for its association with coat color phenotypes. Nine significant signals were
      also found for both traits. The highest signal for each trait was detected by
      both single SNP and haplotype approaches, whereas the smaller signals were not
      consistently detected by the two methods. Altogether these results demonstrated a
      strong genetic control of the "pink" and "pink neck" phenotypes in French Saanen
      goats suggesting that SNP information could be used to identify and remove
      undesired colored animals from the breeding program. 

PMID- 27030981
TI  - Pretreatment PET/CT Standardized Uptake Values Play a Role in Predicting Response
      to Treatment and Survival in Patients with Small Cell Lung Cancer.
AB  - BACKGROUND: We investigated the role of standardized uptake values (SUVs) of the
      primary tumor in small cell lung cancer (SCLC) patients. PATIENTS AND METHODS:
      The relationship between SUV and response to treatment was investigated using
      receiver operating characteristic (ROC) curve analysis, and the efficient cut-off
      value for detecting response to treatment was determined. The effects of SUV on
      response to treatment and survival were investigated. RESULTS: 90 patients with a
      median age of 58 years (range 39-83 years) were included. Median follow-up was 11
      months. The suitable cut-off SUV for determination of response was found to be 10
      in ROC analysis. The sensitivity and specificity of this value were 85.7% (95%
      confidence interval (95% CI) 63-96) and 61.8% (95% CI 49-73) (area under the
      curve 0.783; p = 0.0001), respectively. The overall objective response rate in
      patients with involvement above the cut-off value was 93.3% compared to 59.1% in
      those with involvement below the cut-off value (p < 0.0001). In uni- and
      multivariate analysis, favorable effects of limited-stage disease on response to
      treatment were established (p < 0.05). The effect of an SUV higher than the cut
      off value on progression-free survival was borderline (p = 0.085). CONCLUSION:
      These data may contribute to identifying prognostic disease characteristics and
      response to treatment.

PMID- 27030979
TI  - What we know about nonsteroidal anti-inflammatory drug hypersensitivity.
AB  - Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the
      treatment of inflammatory diseases, but their use is frequently related to
      hypersensitivity reactions. This review outlines our current knowledge of NSAID
      hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic
      mechanisms, as well as diagnosis and treatment. The presentation of NHS varies
      from a local (skin and/or airways) reaction to systemic reactions, including
      anaphylaxis. At the molecular level, NHS reactions can be classified as cross
      reactive (mediated by cyclooxygenase inhibition) or selective (specific
      activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and
      epigenetic factors have been shown to be closely associated with NHS, and may be
      useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests
      are applied, with the exclusion of any cross-reactive NSAIDs. For patients
      diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and
      pharmacological treatment, including biologics, is often used to control their
      respiratory and cutaneous symptoms. Finally, desensitization is recommended only
      for selected patients with NHS. However, further research is required to develop
      new diagnostic methods and more effective treatments against NHS. 

PMID- 27030983
TI  - Simulation of Lake Victoria Circulation Patterns Using the Regional Ocean
      Modeling System (ROMS).
AB  - Lake Victoria provides important ecosystem services including transport, water
      for domestic and industrial uses and fisheries to about 33 million inhabitants in
      three East African countries. The lake plays an important role in modulating
      regional climate. Its thermodynamics and hydrodynamics are also influenced by
      prevailing climatic and weather conditions on diel, seasonal and annual scales.
      However, information on water temperature and circulation in the lake is limited
      in space and time. We use a Regional Oceanographic Model System (ROMS) to
      simulate these processes from 1st January 2000 to 31st December 2014. The model
      is based on real bathymetry, river runoff and atmospheric forcing data using the
      bulk flux algorithm. Simulations show that the water column exhibits annual
      cycles of thermo-stratification (September-May) and mixing (June-August). Surface
      water currents take different patterns ranging from a lake-wide northward flow to
      gyres that vary in size and number. An under flow exists that leads to the
      formation of upwelling and downwelling regions. Current velocities are highest at
      the center of the lake and on the western inshore waters indicating enhanced
      water circulation in those areas. However, there is little exchange of water
      between the major gulfs (especially Nyanza) and the open lake, a factor that
      could be responsible for the different water quality reported in those regions.
      Findings of the present study enhance understanding of the physical processes
      (temperature and currents) that have an effect on diel, seasonal, and annual
      variations in stratification, vertical mixing, inshore-offshore exchanges and
      fluxes of nutrients that ultimately influence the biotic distribution and trophic
      structure. For instance information on areas/timing of upwelling and vertical
      mixing obtained from this study will help predict locations/seasons of high
      primary production and ultimately fisheries productivity in Lake Victoria. 

PMID- 27030982
TI  - Human Pluripotent Stem Cells and Derived Neuroprogenitors Display Differential
      Degrees of Susceptibility to BH3 Mimetics ABT-263, WEHI-539 and ABT-199.
AB  - Human embryonic stem cells (hESCs) are hypersensitive to genotoxic stress and
      display lower survival ability relative to their differentiated progeny. Herein,
      we attempted to investigate the source of this difference by comparing the DNA
      damage responses triggered by the topoisomerase I inhibitor camptothecin, in
      hESCs, human induced pluripotent stem cells (hiPSCs) and hESCs-derived
      neuroprogenitors (NP). We observed that upon camptothecin exposure pluripotent
      stem cells underwent apoptosis more swiftly and at a higher rate than
      differentiated cells. However, the cellular response encompassing ataxia
      telangiectasia mutated kinase activation and p53 phosphorylation both on serine
      15 as well as on serine 46 resulted very similar among the aforementioned cell
      types. Importantly, we observed that hESCs and hiPSCs express lower levels of the
      anti-apoptotic protein Bcl-2 than NP. To assess whether Bcl-2 abundance could
      account for this differential response we treated cells with ABT-263, WEHI-539
      and ABT-199, small molecules that preferentially target the BH3-binding pocket of
      Bcl-xL and/or Bcl-2 and reduce their ability to sequester pro-apoptotic factors.
      We found that in the absence of stress stimuli, NP exhibited a higher sensitivity
      to ABT- 263 and WEHI-539 than hESCs and hiPSCs. Conversely, all tested cell types
      appeared to be highly resistant to the Bcl-2 specific inhibitor, ABT-199.
      However, in all cases we determined that ABT-263 or WEHI-539 treatment
      exacerbated camptothecin-induced apoptosis. Importantly, similar responses were
      observed after siRNA-mediated down-regulation of Bcl-xL or Bcl-2. Taken together,
      our results suggest that Bcl-xL contrary to Bcl-2 contributes to ensure cell
      survival and also functions as a primary suppressor of DNA double-strand brake
      induced apoptosis both in pluripotent and derived NP cells. The emerging
      knowledge of the relative dependence of pluripotent and progenitor cells on Bcl-2
      and Bcl-xL activities may help to predict cellular responses and potentially
      manipulate these cells for therapeutic purposes in the near future. 

PMID- 27030984
TI  - The ORF4 protein of porcine circovirus type 2 antagonizes apoptosis by
      stabilizing the concentration of ferritin heavy chain through physical
      interaction.
AB  - Porcine circovirus type 2 (PCV2) is the primary aetiological agent of porcine
      circovirus-associated disease in swine. The mechanism of PCV2 pathogenesis
      remains largely unknown. A newly identified viral protein of PCV2, ORF4, has been
      suggested to be involved in virus-induced apoptosis. However, there is still no
      information regarding the molecular mechanism by which ORF4 regulates apoptosis.
      In this study, we reveal that a physical interaction between the PCV2 ORF4
      protein and ferritin heavy chain (FHC) in the cytoplasm of host cells reduced the
      cellular concentration of FHC. The ORF4-mediated reduction of FHC inhibited
      reactive oxygen species accumulation in PCV2-infected cells. Consequently, the
      ORF4 protein inhibited apoptosis in host cells. This may be the first report to
      describe the mechanism of ORF4 cytoprotection against apoptosis during the early
      stages of PCV2 infection.

PMID- 27030985
TI  - Upregulation of KLHDC4 Predicts a Poor Prognosis in Human Nasopharyngeal
      Carcinoma.
AB  - Kelch proteins are implicated in the pathogenesis of many human diseases,
      including cancer. Nasopharyngeal carcinoma (NPC) is a rare malignancy in most
      countries, but prevalent in southern China and certain areas of Southeast Asia.
      In this study, we identified Kelch Domain Containing 4 (KLHDC4), an orphan member
      of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the
      expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a
      substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal
      nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T
      classification (P <0.05), N classification (P <0.05) and total staging (P <0.01)
      in NPC, and patients with higher KLHDC4 expression had poorer overall (P <0.01)
      and metastasis-free survival (P <0.05) rates. Knockout (KO) of KLHDC4 via
      CRISPR/Cas9-mediated gene editing in NPC cell line dramatically inhibited cell
      proliferation, colony formation in soft agar and tumor formation in nude mice. In
      addition, cell migration and invasion were also impaired by KLHDC4 depletion as
      revealed by wound healing and Transwell assay. Mechanically, loss of KLHDC4
      markedly induced spontaneous apoptosis in NPC cells, as evidenced by increased
      levels of cleaved caspase-3 and cleaved PARP. Consistently, KLHDC4 knockout cell
      derived xenografts also showed elevated cleaved caspase-3 and PARP but reduced Ki
      67 staining. In conclusion, our results suggest that KLHDC4 promotes NPC
      oncogenesis by suppressing cellular apoptosis. Thus, KLHDC4 may serve as a
      prognosis biomarker and a potential therapeutic target for NPC. 

PMID- 27030986
TI  - An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular
      Therapy of Neuroblastoma and Other Cancers.
AB  - Neuroblastoma is the commonest extra cranial solid cancer of childhood. Despite
      escalation of treatment regimens, a significant minority of patients die of their
      disease. Disialoganglioside (GD2) is consistently expressed at high-levels in
      neuroblastoma tumors, which have been targeted with some success using
      therapeutic monoclonal antibodies. GD2 is also expressed in a range of other
      cancer but with the exception of some peripheral nerves is largely absent from
      non-transformed tissues. Chimeric Antigen Receptors (CARs) are artificial type I
      proteins which graft the specificity of a monoclonal antibody onto a T-cell.
      Clinical data with early CAR designs directed against GD2 have shown some promise
      in Neuroblastoma. Here, we describe a GD2-targeting CAR retroviral cassette,
      which has been optimized for CAR T-cell persistence, efficacy and safety. 

PMID- 27030987
TI  - Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical
      Benefit in Head and Neck Cancer Patients.
AB  - PURPOSE: To compare the clinical benefit of robust optimized Intensity Modulated
      Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation
      Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The
      clinical benefit is quantified in terms of both Normal Tissue Complication
      Probability (NTCP) and target coverage in the case of setup and range errors.
      METHODS AND MATERIALS: For 10 HNC patients, PTV-based IMRT (7 fields), minimax
      and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness.
      Robust optimized plans differed from PTV-based plans in that they target the CTV
      and penalize possible error scenarios, instead of using the static isotropic CTV
      PTV margin. Perturbed dose distributions of all plans were acquired by simulating
      in total 8060 setup (+/-3.5 mm) and range error (+/-3%) combinations. NTCP models
      for xerostomia and dysphagia were used to predict the clinical benefit of IMPT
      versus IMRT. RESULTS: The robustness criterion was met in the IMRT and minimax
      IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV
      based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions
      in minimax IMPT plans compared to IMRT. For these patients, xerostomia and
      dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0-21.1) and 8.1% (95% CI;
      4.9-11.2) on average with minimax IMPT. Increasing the number of fields did not
      contribute to plan robustness, but improved organ sparing. CONCLUSIONS: The
      estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is
      greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the
      target coverage of minimax IMPT plans in the presence of errors was comparable to
      IMRT plans.

PMID- 27030988
TI  - The Principal Forces of Oocyte Polarity Are Evolutionary Conserved but May Not
      Affect the Contribution of the First Two Blastomeres to the Blastocyst
      Development in Mammals.
AB  - Oocyte polarity and embryonic patterning are well-established features of
      development in lower species. Whether a similar form of pre-patterning exists in
      mammals is currently under hot debate in mice. This study investigated this issue
      for the first time in ovine as a large mammal model. Microsurgical trisection of
      unfertilized MII-oocytes revealed that cortical cytoplasm around spindle (S)
      contained significant amounts of total maternal mRNAs and proteins compared to
      matched cytoplast hemispheres that were located either near (NS) or far (FS) -to
      spindle. RT-qPCR provided striking examples of maternal mRNA localized to
      subcellular substructures S (NPM2, GMNN, H19, PCAF, DNMT3A, DNMT1, and STELLA),
      NS (SOX2, NANOG, POU5F1, and TET1), and FS (GCN) of MII oocyte. Immunoblotting
      revealed that specific maternal proteins DNMT3A and NANOG were asymmetrically
      enriched in MII-spindle-half of the oocytes. Topological analysis of sperm entry
      point (SEP) revealed that sperm preferentially entered via the MII-spindle-half
      of the oocytes. Even though, the topological position of first cleavage plane
      with regard to SEP was quite stochastic. Spatial comparison of lipid content
      revealed symmetrical distribution of lipids between 2-cell blastomeres. Lineage
      tracing using Dil, a fluorescent dye, revealed that while the progeny of leading
      blastomere of 2-cell embryos contributed to more cells in the developed
      blastocysts compared to lagging counterpart, the contributions of leading and
      lagging blastomeres to the embryonic-abembryonic parts of the developed
      blastocysts were almost unbiased. And finally, separated sister blastomeres of 2
      cell embryos had an overall similar probability to arrest at any stage before the
      blastocyst (2-cell, 4-cell, 8-cell, and morula) or to achieve the blastocyst
      stage. It was concluded that the localization of maternal mRNAs and proteins at
      the spindle are evolutionarily conserved between mammals unfertilized ovine
      oocyte could be considered polar with respect to the spatial regionalization of
      maternal transcripts and proteins. Even though, the principal forces of this
      definitive oocyte polarity may not persist during embryonic cleavages. 

PMID- 27030989
TI  - Overexpression and Biological Function of Ubiquitin-Specific Protease 42 in
      Gastric Cancer.
AB  - Ubiquitin-specific protease 42 (USP42) is a member of deubiquitinating enzymes
      (DUBs). The alterations of DUBs are implicated in the pathogenesis of a wide
      variety of tumors. However, there are few studies on the expression and
      biological function of USP42 in gastric cancer (GC). Here, the expression levels
      of USP42 were significantly higher in GC tissues than in non-tumorous tissues.
      USP42 expression was significantly correlated with tumor size, TNM stage, lymph
      node metastasis and overall survival of patients with GC. Moreover, USP42
      silencing in two GC cell lines, AGS and MKN-45, notably inhibited cell
      proliferation, but stimulated G1 phase arrest. The proteins promoting cell cycle
      progression (Cyclin D1, Cyclin E1 and PCNA) were down-regulated in USP42
      suppressed cells. Moreover, inhibition of USP42 in GC cells impaired cell
      invasion via affecting the expression of matrix metalloproteinases (MMPs) and
      epithelial-mesenchymal transition (EMT) regulators. In conclusion, USP42
      overexpression could be a potential prognostic marker for GC, regulate the
      survival and invasive properties of GC, and may represent a novel therapeutic
      molecular target for this tumor. 

PMID- 27030990
TI  - The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with
      Nasopharyngeal Carcinoma; A Retrospective Study.
AB  - PURPOSE: In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to
      radiotherapy treatment. Previous study showed a prolonged overall treatment time
      (OTT), due to interruptions during treatment. This study explores the association
      between clinical outcome and OTT. Secondary, the relation between clinical
      outcome and disease stage, waiting time to radiation (WT) and chemotherapy
      schedule was explored. METHODS: In this retrospective cohort, 142 patients who
      started curative intent radiotherapy for NPC between March 2009 and May 2014,
      with or without chemotherapy, were included. The median follow up time was 1.9
      years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule.
      Time factors were log-transformed. Clinical outcome was defined as therapy
      response, loco-regional control (LRC), disease free survival (DFS) and overall
      survival (OS). RESULTS: The median WT was 117 days (range 12-581) and OTT was 58
      days (43-142). OTT and disease stage were not associated to any of the clinical
      outcome parameters. The log-WT was associated to poor therapy outcome (HR 1.68;
      95% ci: 1.09-2.61), LRC (HR 1.66; 95% ci: 1.15-2.39), and DFS (HR 1.4; 95% ci:
      1.09-1.81). In the multivariable analysis, significant hazard risk for poor
      therapy response, LRC, DFS and OS were seen for patients who didn't received
      concurrent chemotherapy. CONCLUSION: Not receiving concurrent chemotherapy showed
      the strongest risk for poor outcome. Since the choice of chemotherapy is related
      to a variety of factors, like the WT and patient's physical condition when
      radiation can start, careful interpretation is needed. Reason for not finding a
      relation between OTT and clinical outcome might be the low number of patients who
      finished radiotherapy within 7 weeks, or by a stronger detrimental effect of
      other factors.

PMID- 27030991
TI  - Predicting dropout using student- and school-level factors: An ecological
      perspective.
AB  - High school dropout has been associated with negative outcomes, including
      increased rates of unemployment, incarceration, and mortality. Dropout rates vary
      significantly depending on individual and environmental factors. The purpose of
      our study was to use an ecological perspective to concurrently explore student-
      and school-level predictors associated with dropout for the purpose of better
      understanding how to prevent it. We used the Education Longitudinal Study of 2002
      dataset. Participants included 14,106 sophomores across 684 public and private
      schools. We identified variables of interest based on previous research on
      dropout and implemented hierarchical generalized linear modeling. In the final
      model, significant student-level predictors included academic achievement,
      retention, sex, family socioeconomic status (SES), and extracurricular
      involvement. Significant school-level predictors included school SES and school
      size. Race/ethnicity, special education status, born in the United States,
      English as first language, school urbanicity, and school region did not
      significantly predict dropout after controlling for the aforementioned
      predictors. Implications for prevention and intervention efforts within a
      multitiered intervention model are discussed. (PsycINFO Database Record

PMID- 27030992
TI  - Notes from the Field: Baseline Assessment of the Use of Ebola Rapid Diagnostic
      Tests--Forecariah, Guinea, October-November 2015.
AB  - The Ebola virus disease (Ebola) epidemic in West Africa began in Guinea in early
      2014. The reemergence of Ebola and risk of ongoing, undetected transmission
      continues because of the potential for sexual transmission and other as yet
      unknown transmission pathways. On March 17, 2016, two new cases of Ebola in
      Guinea were confirmed by the World Health Organization. This reemergence of Ebola
      in Guinea is the first since the original outbreak in the country was declared
      over on December 29, 2015. The prefecture of Forecariah, in western Guinea, was
      considerably affected by Ebola in 2015, with an incidence rate of 159 cases per
      100,000 persons. Guinea also has a high prevalence of malaria; in a nationwide
      2012 survey, malaria prevalence was reported to be 44% among healthy children
      aged <=5 years. Malaria is an important reason for seeking health care; during
      2014, 34% of outpatient consultations were related to malaria.

PMID- 27030993
TI  - Negative emotionality and its facets moderate the effects of exposure to
      Hurricane Sandy on children's postdisaster depression and anxiety symptoms.
AB  - According to diathesis-stress models, temperament traits such as negative
      emotionality (NE) may moderate the effects of stressors on the development of
      symptoms of psychopathology, although little research has tested such models in
      children. Moreover, there are few data on whether specific facets of NE (sadness,
      fear, or anger) may specifically moderate the effects of stress on depression
      versus anxiety. Finally, there is a paucity of research examining whether
      childhood temperament moderates the effect of disaster exposure on depressive or
      anxiety symptoms. Hurricane Sandy, which affected many thousands of people in New
      York State and the surrounding regions in October 2012, offers a unique
      opportunity to address these gaps. Seven to eight years prior to Hurricane Sandy,
      332 children 3 years old completed lab-based measures of NE and its facets. Six
      years later, when they were 9 years old, each mother rated her child's depressive
      and anxiety symptoms. Approximately 8 weeks post-Sandy (an average of 1 year
      after the age 9 assessment), mothers again rated their child's depressive and
      anxiety symptoms, as well as a measure of exposure to stress from Hurricane
      Sandy. Adjusting for symptom levels at age 9, higher levels of stress from
      Hurricane Sandy predicted elevated levels of depressive symptoms only in
      participants with high levels of temperamental sadness and predicted elevated
      levels of anxiety symptoms only in participants high in temperamental
      fearfulness. These findings support the role of early childhood temperament as a
      diathesis for psychopathology and highlight the importance of considering facets
      of temperament when examining their relationship to psychopathology. (PsycINFO
      Database Record

PMID- 27030994
TI  - The network structure of psychopathology in a community sample of preadolescents.
AB  - Psychopathology is often classified according to diagnostic categories or scale
      scores. These ignore potentially important information about associations between
      specific symptoms and, consequently, lead to heterogeneous constructs that may
      mask relevant individual differences. Network analyses focus on these specific
      symptom associations, providing the opportunity to explore the complex structure
      of psychopathology in more detail. We examined the empirical network structure of
      95 emotional and behavioral problems of the Youth Self-Report (YSR) to explore
      how well this structure reflected the predefined YSR domains. The study was
      conducted in a large community sample (N = 2,175) of preadolescents (mean age =
      11.1, SD = 0.6 years), and the network structure was determined by means of the
      recently developed network analysis technique, eLasso. Although problems within
      the same domain, in general, showed more and stronger connections than problems
      belonging to different domains, some problems showed substantially more or
      stronger associations than others; consequently, problems cannot be considered
      interchangeable indicators of their domain. Furthermore, no sharp boundaries were
      found between the domains as specific symptom pairs of different domains showed
      strong connections. Taken together, our findings indicate that network models
      provide a promising addition to the more traditional way of distinguishing
      diagnoses or scale scores. (PsycINFO Database Record

PMID- 27030995
TI  - Visual integration dysfunction in schizophrenia arises by the first psychotic
      episode and worsens with illness duration.
AB  - Visual integration dysfunction characterizes schizophrenia, but prior studies
      have not yet established whether the problem arises by the first psychotic
      episode or worsens with illness duration. To investigate the issue, we compared
      chronic schizophrenia patients (SZs), first episode psychosis patients (FEs), and
      well-matched healthy controls on a brief but sensitive psychophysical task in
      which subjects attempted to locate an integrated shape embedded in noise. Task
      difficulty depended on the number of noise elements co-presented with the shape.
      For half of the experiment, the entire display was scaled down in size to produce
      a high spatial frequency (HSF) condition, which has been shown to worsen patient
      integration deficits. Catch trials-in which the circular target appeared without
      noise-were also added so as to confirm that subjects were paying adequate
      attention. We found that controls integrated contours under noisier conditions
      than FEs, who, in turn, integrated better than SZs. These differences, which were
      at times large in magnitude (d = 1.7), clearly emerged only for HSF displays.
      Catch trial accuracy was above 95% for each group and could not explain the
      foregoing differences. Prolonged illness duration predicted poorer HSF
      integration across patients, but age had little effect on controls, indicating
      that the former factor was driving the effect in patients. Taken together, a
      brief psychophysical task efficiently demonstrates large visual integration
      impairments in schizophrenia. The deficit arises by the first psychotic episode,
      worsens with illness duration, and may serve as a biomarker of illness
      progression. (PsycINFO Database Record

PMID- 27030996
TI  - Gendered contexts: Psychopathy and drug use in relation to sex work and exchange.
AB  - Few scholars have examined psychopathology correlates of sex work. It has been
      suggested that sex work may reflect manifestations of impulsive-antisocial
      psychopathic traits (e.g., reckless disregard, delinquency) in women more than
      men. The current work examined relative contributions of drug dependence and
      distinct psychopathic features in relation to traditional forms of sex work
      (i.e., prostitution) in women, along with gender differences in psychopathy
      relationships with casual forms of sex exchange (i.e., trading sex for
      necessities). Study 1 included 171 community-dwelling women offenders, and Study
      2 included 319 participants (42.3% women) with histories of drug use and/or
      violence. Participants completed the Psychopathy Checklist: Screening Version,
      prostitution was measured as self-report and/or public record data across
      studies, and sex exchange in Study 2 was assessed using a questionnaire based on
      prior research on sexual risk-taking. Findings across both studies demonstrated
      that although psychopathic traits, particularly impulsive-antisocial features,
      were associated with prostitution in women above the use of drugs, drug
      dependence did not moderate the relationship between psychopathic traits and
      prostitution in women. Analyses of Study 2 data revealed that impulsive
      antisocial traits were associated with sex exchange at low, but not high, levels
      of interpersonal-affective traits across participants. As well, interpersonal
      affective traits were significantly positively related to sex exchange in men and
      not significantly (and negatively) related in women. In sum, impulsive-antisocial
      traits related to prostitution among women, suggesting that women may manifest
      these traits within intimate contexts. Moreover, findings indicated gender
      differences in the manifestation of interpersonal-affective traits within sexual
      exchange contexts. (PsycINFO Database Record

PMID- 27030997
TI  - Reduced graphene oxide nanosheets decorated with Au-Pd bimetallic alloy
      nanoparticles towards efficient photocatalytic degradation of phenolic compounds
      in water.
AB  - Reduced graphene oxide nanosheets decorated with Au-Pd bimetallic alloy
      nanoparticles are successfully prepared via a chemical approach consisting of
      reducing the metal precursors using ascorbic acid as reductant at an elevated
      temperature. The prepared nanocomposite is employed as a photocatalyst for the
      degradation of organic contaminants such as phenol, 2-chlorophenol (2-CP), and 2
      nitrophenol (2-NP). The complete degradation of phenol is achieved after 300 min
      under natural sunlight irradiation whereas the degradation of 2-CP and 2-NP is
      completed after 180 min. The activity of the photocatalyst is evaluated
      considering several parameters such as the initial phenol concentration, the
      photocatalyst loading, and the pH of the solution. The degradation kinetics of
      all the compounds is carefully studied and found to follow a linear Langmuir
      Hinshelwood model. Furthermore, the reusability of the photocatalyst is
      successfully achieved up to five cycles and the catalyst exhibits an excellent
      stability. 

PMID- 27030998
TI  - Correction to Monolithically Integrated InGaAs Nanowires on 3D Structured Silicon
      on-Insulator as a New Platform for Full Optical Links.

PMID- 27030999
TI  - Self-oscillating Gel Accelerated while Sensing the Shape of an Aqueous Surface.
AB  - The reciprocating motion of a self-oscillating square gel induced by the Belousov
      Zhabotinsky (BZ) reaction was investigated on an aqueous surface. The chemical
      wave propagated from the side at which the oxidation of the Ru catalyst in the
      gel started. As the chemical wave propagated, the gel moved in either the
      opposite (mode I) or the same (mode II) direction as the chemical wave
      propagation. The gel then went back as the Ru catalyst in the gel was slowly
      reduced. We examined the relationship between the modes of motion (mode I or II)
      and the shape of the aqueous BZ solution surface. The mode selection was
      discussed in relation to the contact angle around the gel which was changed by
      the BZ reaction, i.e., the lateral imbalance of surface tension and the capillary
      interaction.

PMID- 27031000
TI  - HFEPR and Computational Studies on the Electronic Structure of a High-Spin
      Oxidoiron(IV) Complex in Solution.
AB  - Nonheme iron enzymes perform diverse and important functions in biochemistry. The
      active form of these enzymes comprises the ferryl, oxidoiron(IV), [FeO](2+) unit.
      In enzymes, this unit is in the high-spin, quintet, S = 2, ground state, while
      many synthetic model compounds exist in the spin triplet, S = 1, ground state.
      Recently, however, Que and co-workers reported an oxidoiron(IV) complex with a
      quintet ground state, [FeO(TMG3tren)](OTf)2, where TMG3tren = 1,1,1-tris{2-[N2
      (1,1,3,3-tetramethylguanidino)]ethyl}amine and OTf = CF3SO3(-). The trigonal
      geometry imposed by this ligand, as opposed to the tetragonal geometry of earlier
      model complexes, favors the high-spin ground state. Although [FeO(TMG3tren)](2+)
      has been earlier probed by magnetic circular dichroism (MCD) and Mossbauer
      spectroscopies, the technique of high-frequency and -field electron paramagnetic
      resonance (HFEPR) is superior for describing the electronic structure of the
      iron(IV) center because of its ability to establish directly the spin-Hamiltonian
      parameters of high-spin metal centers with high precision. Herein we describe
      HFEPR studies on [FeO(TMG3tren)](OTf)2 generated in situ and confirm the S = 2
      ground state with the following parameters: D = +4.940(5) cm(-1), E = 0.000(5),
      B4(0) = -14(1) * 10(-4) cm(-1), g? = 2.006(2), and g? = 2.03(2). Extraction of a
      fourth-order spin-Hamiltonian parameter is unusual for HFEPR and impossible by
      other techniques. These experimental results are combined with state-of-the-art
      computational studies along with previous structural and spectroscopic results to
      provide a complete picture of the electronic structure of this biomimetic
      complex. Specifically, the calculations reproduce well the spin-Hamiltonian
      parameters of the complex, provide a satisfying geometrical picture of the S = 2
      oxidoiron(IV) moiety, and demonstrate that the TMG3tren is an "innocent" ligand. 

PMID- 27031001
TI  - N(2)-Selective Iodofunctionalization of Olefins with NH-1,2,3-Triazoles to
      provide N(2)-Alkyl-Substituted 1,2,3-Triazoles.
AB  - A new method was developed to synthesize N(2)-alkyl-substituted 1,2,3-triazole
      through N-iodosuccinimide (NIS) mediated iodofuctionalization reaction of the
      alkene group with bi-, mono-, and unsubstituted NH-1,2,3-triazoles. The favored N
      1 type hydrogen bond between the iodonium ion intermediate and 1,2,3-triazole was
      supposed to be generated, which gave the desired N(2)-alkyl triazole with a high
      N(2)-selectivity.

PMID- 27031004
TI  - Language Matters: Race, Trust, and Outcomes in the Pediatric Emergency
      Department.
AB  - OBJECTIVE: Trust in physicians and health care system has been positively
      associated with health care outcomes. The purpose of this study is to explore the
      relationships among race, ethnicity, language, trust, and health care outcomes.
      METHODS: This prospective cross-sectional study took place in the pediatric
      emergency department of an intercity hospital. English- and Spanish-speaking
      guardians were asked to complete a demographic survey, the Pediatric Trust in
      Physicians Scale, and the Group-Based Medical Mistrust Scale. RESULTS: Four
      hundred seventy-five parents were surveyed, of which 21.35% identified as white,
      35.05% as African American, and 53.26% as Hispanic; with respect to language: 88%
      English-speaking and 12% Spanish-speaking. No significant difference was seen in
      trust scores for sex, ethnicity, or religious affiliation. Non-Hispanics and
      English speakers demonstrated an overall higher trust in their physician. English
      speaking participants were found to have higher percentages in all measured
      emergency department variables compared to Spanish speakers, including admittance
      (9.09% and 0.93%, respectively) as well as receiving interventions (42.34% and
      5.53%, respectively). CONCLUSIONS: Our study shows that race and ethnicity
      influence trust and mistrust as well as actual health care outcomes.
      Interestingly, language barrier proved to be one of the greatest causes of health
      care disparities. Therefore, more research is needed to find a way to bridge the
      increasing language barrier between physicians and patients.

PMID- 27031005
TI  - OsWRKY53, a versatile switch in regulating herbivore-induced defense responses in
      rice.
AB  - WRKY proteins, which belong to a large family of plant-specific transcription
      factors, play important roles in plant defenses against pathogens and herbivores
      by regulating defense-related signaling pathways. Recently, a rice WRKY
      transcription factor OsWRKY53 has been reported to function as a negative
      feedback modulator of OsMPK3/OsMPK6 and thereby to control the size of the
      investment a rice plant makes to defend against a chewing herbivore, the striped
      stem borer Chilo suppressalis. We investigated the performance of a piecing
      sucking herbivore, the brown planthopper (BPH) Nilaparvata lugens, on transgenic
      plants that silence or overexpress OsWRKY53, and found that OsWRKY53 activates
      rice defenses against BPH by activating an H2O2 burst and suppressing ethylene
      biosynthesis. These findings suggest that OsWRKY53 functions not only as a
      regulator of plants' investment in specific defenses, but also as a switch to
      initiate new defenses against other stresses, highlighting the versatility and
      importance of OsWRKY53 in herbivore-induced plant defenses. 

PMID- 27031006
TI  - Safety of treatment for gastroparesis.
AB  - INTRODUCTION: Gastroparesis is a syndrome of chronic, often debilitating symptoms
      related to impaired gastric motility, resulting in delayed emptying of the
      stomach, within the setting of a documented absence of any mechanical obstruction
      in the upper gastrointestinal tract. This disorder manifests with the presence of
      early satiety, postprandial fullness, nausea, vomiting, bloating and abdominal
      pain. The past ten years have shown significant advances in knowledge of the
      pathophysiology of this entity as well as in new diagnostic tests. However, in
      the clinical world which requires treatment of gastroparetic symptoms, the
      pharmacological options have been limited and sometimes less than optimal. AREAS
      COVERED: This article provides an overview of the safety of the available
      pharmacological therapies utilized in the treatment of gastroparetic symptoms
      specifically addressing the safety of prokinetics, antiemetics, sensory
      neuromodulators and pain modifying agents. In addition, a brief overview of the
      evolving but yet to be officially approved agents is included. EXPERT OPINION:
      None of the medications used for the treatment of gastroparesis are devoid of
      side effects. Therefore, when prescribing these medications, the risk/benefit
      ratio should be considered. Since those agents are increasingly administered in
      combination, awareness of possible drug interactions must be considered in a
      setting of the patients' medical history, age, systemic diseases and other
      medications.

PMID- 27031007
TI  - Meiotic recombination is suppressed near the histone-defined border of
      euchromatin and heterochromatin on chromosome 2L of Drosophila melanogaster.
AB  - In Drosophila melanogaster, the borders between pericentric heterochromatin and
      euchromatin on the major chromosome arms have been defined in various ways,
      including chromatin-specific histone modifications, the binding patterns of
      heterochromatin-enriched chromosomal proteins, and various cytogenetic
      techniques. Elucidation of the genetic properties that independently define the
      different chromatin states associated with heterochromatin and euchromatin should
      help refine the boundary. Since meiotic recombination is present in euchromatin,
      but absent in heterochromatin, it constitutes a key genetic property that can be
      observed transitioning between chromatin states. Using P element insertion lines
      marked with a su(Hw) insulated mini-white gene, meiotic recombination was found
      to transition in a region consistent with the H3K9me2 transition observed in
      ovaries. 

PMID- 27031008
TI  - Superior efficacy and tolerance of reduced doses of vemurafenib plus anakinra in
      Erdheim-Chester disease: Towards the paradigm of combined targeting and immune
      therapies.

PMID- 27031010
TI  - Epiglottitis: It Hasn't Gone Away.

PMID- 27031009
TI  - Cell and gene therapy strategies to eradicate HIV reservoirs.
AB  - PURPOSE OF REVIEW: Highly active antiretroviral treatment has dramatically
      improved the prognosis for people living with HIV by preventing AIDS-related
      morbidity and mortality through profound suppression of viral replication.
      However, a long-lived viral reservoir persists in latently infected cells that
      harbor replication-competent HIV genomes. If therapy is discontinued, latently
      infected memory cells inevitably reactivate and produce infectious virus,
      resulting in viral rebound. The reservoir is the biggest obstacle to a cure of
      HIV. RECENT FINDINGS: This review summarizes significant advances of the past
      year in the development of cellular and gene therapies for HIV cure. In
      particular, we highlight work done on suppression or disruption of HIV
      coreceptors, vectored delivery of antibodies and antibody-like molecules, T-cell
      therapies and HIV genome disruption. SUMMARY: Several recent advancements in
      cellular and gene therapies have emerged at the forefront of HIV cure research,
      potentially having broad implications for the future of HIV treatment.

PMID- 27031011
TI  - Disseminated Intravascular Coagulation: A Practical Approach.

PMID- 27031012
TI  - A Pilot Study of Age-Related Changes in the Sphingolipid Composition of the Rat
      Sarcoplasmic Reticulum.
AB  - BACKGROUND: Muscle strength declines more rapidly than muscle size, manifesting
      as a loss of muscle quality. One putative contributor to this impairment of
      muscle quality is impaired sarcoplasmic reticulum (SR) function. OBJECTIVES: The
      principal objective of this study was to characterize the sphingolipid
      composition of the SR in adult and aging rat muscles. A secondary, exploratory
      objective was to test for associations between SR sphingolipids and SR function
      (i.e., Ca2+ release). DESIGN: Using an animal model, the objectives were
      evaluated in a pre-clinical, cross-sectional study. SETTING: Data were collected
      in an academic research laboratory. PARTICIPANTS: Medial gastrocnemius muscles of
      adult (n=8; 7-8 months) and aged (n=8; 24-25 months), male F344/BN hybrid rats
      were processed to extract SR. MEASUREMENTS: Sphingolipids in the SR were measured
      using tandem mass spectrometry. Fatty acid concentrations within the major
      sphingolipid classes were evaluated via Principal Component Analysis (PCA). In a
      subset of samples, SR Ca2+ release rates were determined using fluorometric
      methods, and associations with specific (based on results of PCA) fatty acid
      concentrations were evaluated. RESULTS: Aging SR showed an overall decline in the
      ratio of unsaturated to saturated fatty acids. Age-specific differences were
      observed for hexosylceramide and ceramide-1-phosphate. Within subset of samples
      with SR Ca2+ release data, a significant negative association between Ca2+
      release and C1P18:0 and trends for positive associations with hexCER24:0 and 24:1
      were observed. CONCLUSIONS: These preliminary, pre-clinical data suggest that
      changes in SR sphingolipids may play a role in age-related impairment of muscle
      function. Further work is needed to explore this hypothesis, as SR sphingolipids
      may prove a fruitful target for interventions, be they physical (i.e., exercise),
      nutritional or pharmacological.

PMID- 27031013
TI  - Update on Definitions of Sarcopenia.

PMID- 27031014
TI  - The Comparative Frame of Reference in Self-Rated Health Questions Matters When
      Predicting Difficulty with Activities of Daily Living.
AB  - BACKGROUND: Within the assessment of frailty, self-rated health (SRH) questions
      remain frequently used in survey research attempting to quantify a subjective and
      global measure of health. Studies have largely ignored the fact that SRH
      questions may differ in their ability to predict level of difficulty with
      performing activities of daily living (ADLs)-a variance partially influenced by
      whether a comparative frame of reference in used in the SRH question. SPECIFIC
      AIM: Investigate if a Comparative-SRH (C-SRH) question with response options
      ranging on an adjectival scale ranging from 0 to 3; and a Non-Comparative-SRH (NC
      SRH) question with an adjectival response scale from range 0 to 5; differ in
      their ability to predict level of difficulty in performing ADLs after accounting
      for demographic, psychosocial, and related health factors. SETTING AND DESIGN:
      Cross-sectional study of community-dwelling adults (n=275; x age=68; female=54%;
      x BMI=31) from North Carolina participating in the Hispanic Aging Survey (HAS)
      were used in multivariable linear regressions to predict a granular measure of
      level of difficulty performing ADLs. RESULTS: Only C-SRH has a statistically
      significant relationship with ADLs-where each increase in C-SRH (i.e., more
      positively self-rated health) is associated with a decrease in ADL level of
      difficult. CONCLUSIONS: Using a comparative frame of reference in SRH questions
      may have important implications when attempting to understand the statistical
      relationship between self-rated global health and physical function in the
      assessment of frailty in older adults.

PMID- 27031015
TI  - Association of Grip and Knee Extension Strength with Walking Speed of Older Women
      Receiving Home-care Physical Therapy.
AB  - BACKGROUND: Decreased muscle strength and limited physical performance are key
      elements of frailty and sarcopenia. The relative value of grip and knee extension
      strength for explaining walking performance has not been clearly established.
      OBJECTIVES: Compare the ability of grip and knee extension strength to explain
      gait speed. DESIGN: Retrospective use of cross-sectionally obtained data.
      SETTING: Patients' homes. PARTICIPANTS: Forty-four ambulatory women patients at
      least 65 years of age. MEASUREMENTS: Grip and knee extension forces obtained
      bilaterally with dynamometers and comfortable gait speed. RESULTS: Knee extension
      forces were, but grip strength forces were not, correlated significantly with
      gait speed. Knee extension forces were able, but grip strength forces were not
      able, to satisfactorily identify patients with gait speeds <.40 m/sec.
      CONCLUSIONS: For women receiving therapy in a home-care setting, physical
      performance as reflected by gait speed is better explained by knee extension
      strength than by grip strength.

PMID- 27031016
TI  - Relationship between Isometric Strength of Six Lower Limb Muscle Groups and Motor
      Skills among Nursing Home Residents.
AB  - This research aimed to assess the correlation between isometric muscle strength
      of the lower limb and motor skills. This is a cross sectional study performed
      among volunteer nursing home residents included in the SENIOR (Sample of Elderly
      Nursing home Individuals: an Observational Research) cohort. The present analysis
      focused on isometric muscle strength of 6 lower limb muscle groups (i.e. knee
      extensors, knee flexors, hip abductors, hip extensors, ankle flexors and ankle
      extensors), assessed using a validated hand-held dynamometer (i.e. the MicroFET2
      device), and motor skills evaluated using the Tinetti test, the Timed Up and Go
      test, the Short Physical Performance Battery test (SPPB) and the walking speed.
      The relationship between all these parameters was tested by means of a multiple
      correlation, adjusted on age, sex and body mass index. 450 nursing home residents
      (69.8% of women) with a mean age of 83.1+/-9.4 years were included in this study.
      Our results showed a significant inverse correlation between lower limb muscle
      strength and the time required to perform the TUG test or gait speed, except for
      ankle flexors and ankle extensors. The relationship between the Tinetti test or
      the SPPB score, and lower limb muscle strength was significant, except for ankle
      flexors and ankle extensors. In conclusion, a positive association between lower
      limb muscle strength of the four main muscle groups and motor skills of the
      elderly nursing residents was found in this research. Therefore, special
      attention should be given to these muscle groups during rehabilitation programs. 

PMID- 27031017
TI  - Older Adults with Chronic Low Back Pain: A Clinical Population Vulnerable to
      Frailty?
AB  - The purpose of this secondary analysis was to explore the differences in
      proportions of frailty criteria, pre-frailty, and frailty in older adults with
      and without chronic low back pain (CLBP). Among individuals with CLBP, we also
      explored whether the proportions of these outcomes differed based on pain
      intensity status. Using measures to determine weakness, slowness, and exhaustion,
      we determined that older adults with CLBP had higher proportions of frailty
      criteria and were more likely to be classified as pre-frail or frail. Older
      adults with high intensity CLBP had greater proportions of weakness, exhaustion,
      and pre-frailty/frailty compared to those with low intensity CLBP. These
      preliminary findings suggest older adults with CLBP may be at a higher risk for
      frailty than those without pain; pain intensity may be an important factor in
      assessing risk of frailty in this population. 

PMID- 27031018
TI  - Living and Health Conditions Associated with Overweight and Obesity among
      Elderly.
AB  - BACKGROUND: The epidemiological and nutritional transition processes in the last
      decades underlie the rising trend of obesity in the elderly and is related to
      increased risk of chronic non-communicable diseases and decreased functional
      status. OBJECTIVE: To analyze the association of demographic, socioeconomic,
      lifestyle and health-related factors with overweight and obesity in elderly.
      DESIGN: Cross-sectional study. SETTING: Carried out in Campinas-Sao Paulo,
      Brazil, in 2011. PARTICIPANTS: 452 non-institutionalized elderly (aged >=60
      years), half were users of a government-run soup kitchen and the other half were
      neighbors of the same sex. RESULTS: Overweight frequency (BMI >=25 and <30 kg/m2)
      was 44.5% and obesity (BMI >=30 kg/m2) was 21.7%. In the multiple multinomial
      logistic regression model adjusted for sex, age group and economic class, there
      was greater chance of overweight among those that reported dyslipidemia; those
      that reported arthritis/ arthrosis/rheumatism and that once or more per week
      replaced supper by a snack were more likely to be obese. Elderly who did not
      leave home daily and reported diabetes had higher chance of overweight and
      obesity. CONCLUSIONS: Overweight and obesity are associated with worse living and
      health-related conditions, such as physical inactivity, changes in eating
      behaviors, and chronic diseases. Public health policies should encourage regular
      physical activity and healthy eating behaviors, focusing on traditional diet,
      through nutritional education, in order to reduce the prevalence of overweight
      and obesity and chronic diseases.

PMID- 27031019
TI  - Innovative Medicines Initiative: The SPRINT Project.

PMID- 27031020
TI  - The Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCg) Attenuates Skeletal
      Muscle Atrophy in a Rat Model of Sarcopenia.
AB  - OBJECTIVE: Sarcopenia-the loss of muscle mass and functionality occurring with
      age-is a pervasive problem with few effective treatments beyond exercise. We
      examined the ability of the green tea catechin, epigallocatechin-3-gallate
      (EGCg), to impact muscle mass and the molecular pathway involved in muscle
      atrophy in a rat model of sarcopenia. METHODS: 20-month-old Sprague-Dawley rats
      were treated for 8 weeks with control diet or control plus 200mg/kg body weight
      of EGCg diet. RESULTS: EGCg-supplemented animals had significantly greater
      gastrocnemius muscle mass than the aged controls, and showed a trend for
      increased muscle fiber cross-sectional areas (CSA) (p=0.06). These changes were
      associated with significantly lower protein expressions of the intramuscular 19S
      and 20S proteasome subunits and the MuRF1 and MAFbx ubiquitin ligases in the EGCg
      treated animals. Proteasome activity as determined by 'Chymotrypsin-like' enzyme
      activity was also significantly reduced by EGCg. Muscle mRNA expression of IL-15
      and IGF-1 were significantly increased in the EGCg group vs. the aged controls.
      In comparison to younger adult animals (6 month), the protein expression of 19S,
      20S, MuRF1, MAFbx, and myostatin were increased between approximately 4- and 12
      fold in the aged controls, but only up to ~2-fold in the aged EGCg animals.
      CONCLUSIONS: EGCg supplementation was able to preserve muscle in sarcopenic rats,
      partly through attenuating protein degradation via the ubiquitin-proteasome
      pathway, together with increased expression of anabolic factors.

PMID- 27031021
TI  - Changes of Body Composition, Muscular Strength and Physical Performance Due to
      Resistance Training in Older Persons with Sarcopenic Obesity.
AB  - BACKGROUND: At present, it is unclear whether older, obese persons with or
      without sarcopenia respond differently to training. Furthermore, there are no
      differentiated recommendations for resistance training for this special target
      group. OBJECTIVES: The objectives are to investigate the changes in the physical
      parameters of older, obese men caused by training and to reappraise the
      modalities of resistance training for older persons. DESIGN: Pre-test-post-test
      design. PARTICIPANTS: The participants were 33 physically inactive and obese
      older men (>= 65 years, BMI >=30 kg/m2), with-out severe diseases. Subjects were
      divided into two groups: NSAR (no or presarcopenia, n= 15) or SAR (sarcopenia, n=
      18). INTERVENTION: The intervention consisted of progressive resistance training,
      twice a week for 16 weeks with finally 80-85% of maximum strength and three sets
      with 8-12 repetitions. The training contained six exercises for the major muscle
      groups. MEASUREMENTS: Sarcopenia was assessed using the Short Physical
      Performance Battery (SPPB), hand-grip strength, skeletal muscle mass index (SMI),
      and gait speed over a 6-meter walkway. Furthermore, the maximum dynamic strength
      (1 RM) was assessed. RESULTS: At baseline, the NSAR group had significantly
      better values in SMI, SPPB score, hand-grip strength, and 1 RM. After training,
      the results in both groups displayed an increase in 1 RM at the lower limbs (NSAR
      18%, SAR 38%) and the upper limbs (NSAR 12%, SAR 14%). Also, the SPPB score (NSAR
      11%, SAR 15%) and the 6-m-gait speed (NSAR 5%, SAR 10%) increased. The SAR group
      was able to increase their right hand-grip strength by 12%, whereas the NSAR
      group maintained their initial high strength values. SMI did not change in both
      groups. CONCLUSIONS: Both groups show improvements after resistance training with
      slightly more benefits for men with sarcopenia. Results of this study can be used
      to define specific training regimens for N(SAR) subjects.

PMID- 27031022
TI  - Modeling the Losses of Dissolved CO(2) from Laser-Etched Champagne Glasses.
AB  - Under standard champagne tasting conditions, the complex interplay between the
      level of dissolved CO2 found in champagne, its temperature, the glass shape, and
      the bubbling rate definitely impacts champagne tasting by modifying the neuro
      physicochemical mechanisms responsible for aroma release and flavor perception.
      On the basis of theoretical principles combining heterogeneous bubble nucleation,
      ascending bubble dynamics, and mass transfer equations, a global model is
      proposed, depending on various parameters of both the wine and the glass itself,
      which quantitatively provides the progressive losses of dissolved CO2 from laser
      etched champagne glasses. The question of champagne temperature was closely
      examined, and its role on the modeled losses of dissolved CO2 was corroborated by
      a set of experimental data.

PMID- 27031024
TI  - An updated evaluation of reported no-observed adverse effect levels for
      chrysotile asbestos for lung cancer and mesothelioma.
AB  - Although consumption of chrysotile asbestos has decreased since the 1970s, the
      latency period of asbestos-related cancers is thought to be at least 20-30 years,
      and therefore the potential health risks associated with historical exposures is
      still actively researched. This analysis represents an update to a previous paper
      in which we evaluated the exposure-response relationships for lung cancer and
      mesothelioma in chrysotile-exposed cohorts. Here, we review several recently
      published studies as well as updated information from previous studies. For each
      of the 14 studies considered, we identified the "no-observed adverse effect
      level" (NOAEL) for lung cancer and/or mesothelioma. NOAEL values for lung cancer
      ranged from 1.1 to <20 f/cc-years to 1600-3200 f/cc-years, and for mesothelioma
      ranged from 100-400 f/cc-years to 800-1599 f/cc-years. The range of "best
      estimate" NOAELs was estimated to be 89-168 f/cc-years for lung cancer and 208
      415 f/cc-years for mesothelioma. None of the six cohorts of cement or friction
      product manufacturing workers exhibited an increased lung cancer risk at any
      exposure level, while all of the five studies of textile workers reported an
      increased risk at one or more exposure levels. This is likely because friction
      and cement workers were exposed to much shorter chrysotile fibers. Of the seven
      cases of peritoneal mesothelioma reported in the included studies, none were
      observed in the analyses of cement or friction product manufacturing workers in
      the absence of crocidolite exposure. These findings will help characterize
      potential worker and consumer health risks associated with historical and current
      chrysotile exposures.

PMID- 27031025
TI  - Effects of the Selected Iminosugar Derivatives on Pseudomonas aeruginosa Biofilm
      Formation.
AB  - A lack of an effective way to eliminate pathogenic bacteria hidden in the biofilm
      is a major problem in the treatment of chronic bacterial infections. Iminosugar
      derivatives are potential candidates for inhibitors of enzymes taking part in the
      biosynthesis of exopolysaccharides, which are forming bacterial biofilm.
      Investigated iminosugars were studied either at an early stage of biofilm
      formation or later on when the mature biofilm of Pseudomonas aeruginosa was
      already formed. A series of diverse iminosugar structures significantly inhibited
      biofilm formation, whereas they showed no influence on already formed biofilm.
      This indicates a possible mechanism of their action based on inhibition of
      exopolysaccharide backbone synthesis in the early stages of biofilm formation.
      Moreover, iminosugar derivatives did not show significant effect on the viable
      bacterial numbers in both early and mature biofilm forms. Importantly, they were
      not cytotoxic against human Caco-2 cells in vitro, which may be to their
      advantage in case of their medical application in preventing P. aeruginosa
      biofilm formation.

PMID- 27031026
TI  - Leveraging Technology: The Macy Report's Recommendation #4.

PMID- 27031027
TI  - Is Education the Cure?
AB  - Requests for educational programs to address a perceived lack of knowledge or
      skill should be evaluated to identify the most appropriate intervention. Through
      careful analysis of the reasons underlying a practice gap, the most appropriate
      and effective approach can be chosen and implemented.

PMID- 27031028
TI  - Interprofessional Collaborative Practice.
AB  - The need for change in the delivery of health care could not be more imminent due
      to the multiple breaches in patient safety occurring in virtually all health care
      settings across the United States and internationally. The concept of health care
      teams working together is not new; however, implementing a culture of change,
      where concepts such as patient safety, mutual respect, shared decision making,
      and patient-centered care is the norm, remains a novel and often fleeting idea in
      most health care facilities.

PMID- 27031029
TI  - Professional Behavior in Nursing.
AB  - Being clear about what constitutes professional behavior is a pathway to
      effective leadership. Not all nurses come out of educational programs with an
      understanding about what aspects of behavior signal true professionalism. This
      article uses the American Organization of Nurse Executives' Nurse Executive
      Competency for Processional Behavior to help professional development nurse
      faculty identify role modeling behavior and other aspects that new nurses can use
      to help them advance in their careers, while improving care to patients and
      families.

PMID- 27031030
TI  - Probing the Relationship Between Evidence-Based Practice Implementation Models
      and Critical Thinking in Applied Nursing Practice.
AB  - HOW TO OBTAIN CONTACT HOURS BY READING THIS ISSUE Instructions: 1.2 contact hours
      will be awarded by Villanova University College of Nursing upon successful
      completion of this activity. A contact hour is a unit of measurement that denotes
      60 minutes of an organized learning activity. This is a learner-based activity.
      Villanova University College of Nursing does not require submission of your
      answers to the quiz. A contact hour certificate will be awarded after you
      register, pay the registration fee, and complete the evaluation form online at
      http://goo.gl/gMfXaf. In order to obtain contact hours you must: 1. Read the
      article, "Probing the Relationship Between Evidence-Based Practice Implementation
      Models and Critical Thinking in Applied Nursing Practice," found on pages 161
      168, carefully noting any tables and other illustrative materials that are
      included to enhance your knowledge and understanding of the content. Be sure to
      keep track of the amount of time (number of minutes) you spend reading the
      article and completing the quiz. 2. Read and answer each question on the quiz.
      After completing all of the questions, compare your answers to those provided
      within this issue. If you have incorrect answers, return to the article for
      further study. 3. Go to the Villanova website to register for contact hour
      credit. You will be asked to provide your name, contact information, and a VISA,
      MasterCard, or Discover card number for payment of the $20.00 fee. Once you
      complete the online evaluation, a certificate will be automatically generated.
      This activity is valid for continuing education credit until March 31, 2019.
      CONTACT HOURS This activity is co-provided by Villanova University College of
      Nursing and SLACK Incorporated. Villanova University College of Nursing is
      accredited as a provider of continuing nursing education by the American Nurses
      Credentialing Center's Commission on Accreditation. OBJECTIVES: * Describe the
      key components and characteristics related to evidence-based practice and
      critical thinking. * Identify the relationship between evidence-based practice
      and critical thinking. DISCLOSURE STATEMENT Neither the planners nor the author
      have any conflicts of interest to disclose. Evidence-based practice is not a new
      concept to the profession of nursing, yet its application and sustainability is
      inconsistent in nursing practice. Despite the expansion of efforts to teach
      evidence-based practice and practically apply evidence at the bedside, a research
      practice gap still exists. Several critical factors contribute to the successful
      application of evidence into practice, including critical thinking. The purpose
      of this article is to discuss the relationship between critical thinking and the
      current evidence-based practice implementation models. Understanding this
      relationship will help nurse educators and clinicians in cultivating critical
      thinking skills in nursing staff to most effectively apply evidence at the
      bedside. Critical thinking is a key element and is essential to the learning and
      implementation of evidence-based practice, as demonstrated by its integration
      into evidence-based practice implementation models.

PMID- 27031032
TI  - Barriers and Facilitators of Utilizing Research Among Nurses in Nepal.
AB  - BACKGROUND: This study determined the perceived barriers to and facilitators of
      Nepalese nurses in utilizing research in the workplace. Evidence-based nursing
      practice provides the synergy for high-quality patient care, but it does not seem
      to be the case in underdeveloped countries, such as Nepal. METHOD: A descriptive,
      cross-sectional study involving 97 nurses from Nepal was conducted. Data were
      collected using the BARRIERS Scale and a facilitator questionnaire. RESULTS: The
      top three barriers to research utilization in Nepalese nurses are (a) research
      reports and articles are not readily available (80.5%), (b) inadequate facilities
      for implementation (75.3%), and (c) research reports and articles are not
      published fast enough (71.6%). The top three facilitators perceived to encourage
      Nepalese nurses to utilize or participate in research are (a) initiation of
      nursing research projects (27.4%), (b) educational update on research methods
      (16.7%), and (c) provision of funding for research (15.5%). CONCLUSION: Findings
      from this study mirror the barriers to research utilization experienced by nurses
      in other countries. Macro- and micro-level support are needed to foster a culture
      of evidence-based practice among Nepalese nurses to empower them in making
      informed decisions based on research in providing quality patient care.

PMID- 27031033
TI  - Dissemination of Evidence-Based Practice to Directors of Nursing by an Outreach
      Campaign in Taiwan.
AB  - BACKGROUND: Directors of nursing (DONs) have an important influence in the
      dissemination of evidence-based practice (EBP) in hospital settings. The current
      study examined how the knowledge, skills, and behaviors of DONs changed when EBP
      was implemented during a 5-year, nationwide promotional campaign providing EBP
      related information resources and promotional activities in regional hospitals in
      Taiwan. METHOD: Cross-sectional questionnaire surveys for a nationwide
      representative sample of DONs were conducted in 2007, 2009, and 2011 to examine
      views related to EBP, including changes in beliefs, attitudes, knowledge, skills,
      behaviors, and barriers. RESULTS: This study enrolled 267 DONs in 2007, 257 in
      2009, and 287 in 2011. During the study period, DONs' EBP knowledge and skills
      increased, but their beliefs and attitudes did not significantly change.
      Furthermore, the use of Internet-based resources, including web portals,
      electronic textbooks, electronic journals, and evidence-based online databases,
      increased. Most barriers significantly declined after the intervention.
      CONCLUSION: DONs' knowledge, skills, and behaviors regarding EBP increased after
      the multifaceted intervention. The data suggest this outreach program is useful
      in disseminating EBP implementation to DONs.

PMID- 27031034
TI  - Web-Based Assessment of Genomic Knowledge Among Practicing Nurses: A Validation
      Study.
AB  - BACKGROUND: Understanding foundational concepts of genetics and genomics is
      essential to contemporary nursing practice. The Genomic Nursing Concept Inventory
      (GNCI) is a research-based measure designed to assess nurses' knowledge of key
      genetic concepts. Developed and tested among nursing students, the GNCI needs to
      be validated with practicing nurses. A valid assessment of genetic-genomic
      knowledge among nurses is vital to support competency-based continuing education.
      METHOD: This study explored the feasibility of employing a Web-based version of
      the GNCI and tested its psychometric performance among a purposive sample of
      practicing nurses. RESULTS: The psychometric features of the GNCI are described
      in terms of scale, subscale, and concept difficulty and internal consistency
      reliability; these values were in an acceptable range. CONCLUSION: This study
      represents a successful early step in testing the feasibility of using a Web
      based version of the GNCI and validating the GNCI to measure genetic-genomic
      knowledge among practicing nurses.

PMID- 27031035
TI  - The effect of an acute sleep hygiene strategy following a late-night soccer match
      on recovery of players.
AB  - Elite soccer players are at risk of reduced recovery following periods of sleep
      disruption, particularly following late-night matches. It remains unknown whether
      improving sleep quality or quantity in such scenarios can improve post-match
      recovery. Therefore, the aim of this study was to investigate the effect of an
      acute sleep hygiene strategy (SHS) on physical and perceptual recovery of players
      following a late-night soccer match. In a randomised cross-over design, two
      highly-trained amateur teams (20 players) played two late-night (20:45) friendly
      matches against each other seven days apart. Players completed an SHS after the
      match or proceeded with their normal post-game routine (NSHS). Over the ensuing
      48 h, objective sleep parameters (sleep duration, onset latency, efficiency, wake
      episodes), countermovement jump (CMJ; height, force production), YoYo
      Intermittent Recovery test (YYIR2; distance, maximum heart rate, lactate), venous
      blood (creatine kinase, urea and c-reactive protein) and perceived recovery and
      stress markers were collected. Sleep duration was significantly greater in SHS
      compared to NSHS on match night (P = 0.002, d = 1.50), with NSHS significantly
      less than baseline (P < 0.001, d = 1.95). Significant greater wake episodes
      occurred on match night for SHS (P = 0.04, d = 1.01), without significant
      differences between- or within-conditions for sleep onset latency (P = 0.12),
      efficiency (P = 0.39) or wake episode duration (P = 0.07). No significant
      differences were observed between conditions for any physical performance or
      venous blood marker (all P > 0.05); although maximum heart rate during the YYIR2
      was significantly higher in NSHS than SHS at 36 h post-match (P = 0.01; d =
      0.81). There were no significant differences between conditions for perceptual
      "overall recovery" (P = 0.47) or "overall stress" (P = 0.17). Overall, an acute
      SHS improved sleep quantity following a late-night soccer match; albeit without
      any improvement in physical performance, perceptual recovery or blood-borne
      markers of muscle damage and inflammation.

PMID- 27031036
TI  - Risk of Miscarriage in Women Receiving Antidepressants in Early Pregnancy,
      Correcting for Induced Abortions.
AB  - BACKGROUND: Earlier studies on the association between antidepressant use and
      miscarriage have obtained conflicting results after accounting for the role of
      depression, and none have taken into account the high risk of induced abortions
      in women using antidepressants. METHODS: We identified 41,964 pregnant women
      delivering between 1998 and 2002 using Quebec's health administration databases.
      We compared women prescribed antidepressants in the first trimester and with a
      recorded diagnosis of depression before pregnancy to (1) women with neither
      antidepressant use nor a depression diagnosis before or during pregnancy; (2)
      women with a depression diagnosis before pregnancy, but no antidepressants
      prescribed in the first trimester; and (3) women prescribed hypothyroid
      medication in the first trimester, but not antidepressants. We used log binomial
      regression to assess the adjusted relative risk of miscarriage, corrected for
      induced abortion risk. RESULTS: The miscarriage risk uncorrected for induced
      abortions was 16%, 10%, and 9% for depressed women exposed to antidepressants;
      unexposed depressed women; and unexposed, nondepressed women, respectively. These
      decreased to 11%, 8%, and 7% after correction for induced abortions. In
      multivariable analysis, the corrected risk of miscarriage relative to unexposed,
      nondepressed women was 1.3 (1.1-1.5) for antidepressant-exposed women and 1.1
      (1.0-1.2) for unexposed depressed women. The miscarriage relative risk for
      antidepressant users compared with unexposed depressed women was thus 1.2 (1.0
      1.4). CONCLUSIONS: Antidepressant use in the first trimester is associated with
      an increased risk of miscarriage when compared with either nondepressed or
      depressed unexposed women, even after accounting for induced abortions.

PMID- 27031037
TI  - Targeted Maximum Likelihood Estimation for Pharmacoepidemiologic Research.
AB  - BACKGROUND: Targeted maximum likelihood estimation has been proposed for
      estimating marginal causal effects, and is robust to misspecification of either
      the treatment or outcome model. However, due perhaps to its novelty, targeted
      maximum likelihood estimation has not been widely used in pharmacoepidemiology.
      The objective of this study was to demonstrate targeted maximum likelihood
      estimation in a pharmacoepidemiological study with a high-dimensional covariate
      space, to incorporate the use of high-dimensional propensity scores into this
      method, and to compare the results to those of inverse probability weighting.
      METHODS: We implemented the targeted maximum likelihood estimation procedure in a
      single-point exposure study of the use of statins and the 1-year risk of all
      cause mortality postmyocardial infarction using data from the UK Clinical
      Practice Research Datalink. A range of known potential confounders were
      considered, and empirical covariates were selected using the high-dimensional
      propensity scores algorithm. We estimated odds ratios using targeted maximum
      likelihood estimation and inverse probability weighting with a variety of
      covariate selection strategies. RESULTS: Through a real example, we demonstrated
      the double robustness of targeted maximum likelihood estimation. We showed that
      results with this method and inverse probability weighting differed when a large
      number of covariates were included in the treatment model. CONCLUSIONS: Targeted
      maximum likelihood can be used in high-dimensional covariate settings. In high
      dimensional covariate settings, differences in results between targeted maximum
      likelihood and inverse probability weighted estimation are likely due to
      sensitivity to (near) positivity violations. Further investigations are needed to
      gain better understanding of the advantages and limitations of this method in
      pharmacoepidemiological studies.

PMID- 27031038
TI  - Regression Discontinuity Design: Simulation and Application in Two Cardiovascular
      Trials with Continuous Outcomes.
AB  - In epidemiology, the regression discontinuity design has received increasing
      attention recently and might be an alternative to randomized controlled trials
      (RCTs) to evaluate treatment effects. In regression discontinuity, treatment is
      assigned above a certain threshold of an assignment variable for which the
      treatment effect is adjusted in the analysis. We performed simulations and a
      validation study in which we used treatment effect estimates from an RCT as the
      reference for a prospectively performed regression discontinuity study. We
      estimated the treatment effect using linear regression adjusting for the
      assignment variable both as linear terms and restricted cubic spline and using
      local linear regression models. In the first validation study, the estimated
      treatment effect from a cardiovascular RCT was -4.0 mmHg blood pressure (95%
      confidence interval: -5.4, -2.6) at 2 years after inclusion. The estimated effect
      in regression discontinuity was -5.9 mmHg (95% confidence interval: -10.8, -1.0)
      with restricted cubic spline adjustment. Regression discontinuity showed
      different, local effects when analyzed with local linear regression. In the
      second RCT, regression discontinuity treatment effect estimates on total
      cholesterol level at 3 months after inclusion were similar to RCT estimates, but
      at least six times less precise. In conclusion, regression discontinuity may
      provide similar estimates of treatment effects to RCT estimates, but requires the
      assumption of a global treatment effect over the range of the assignment
      variable. In addition to a risk of bias due to wrong assumptions, researchers
      need to weigh better recruitment against the substantial loss in precision when
      considering a study with regression discontinuity versus RCT design.

PMID- 27031039
TI  - Longitudinal Associations of Phthalate Exposures During Childhood and Body Size
      Measurements in Young Girls.
AB  - BACKGROUND: Phthalates are environmental chemicals that may play a role in the
      development of obesity. Few studies have investigated longitudinal associations
      between postnatal phthalate exposures and subsequent anthropometric measurements
      in children. METHODS: We collected data as part of The Breast Cancer and
      Environment Research Program at three US sites. A total of 1,239 girls, aged 6-8
      years, were enrolled in 2004-2007. We categorized baseline phthalate exposures,
      assessed from creatinine-corrected urinary concentrations of low-molecular weight
      phthalate metabolites, as low, <78; medium, 78 to <194; and high, >=194 MUg/g
      creatinine and of high-molecular weight phthalates as low, <111; medium, 111-278;
      and high, >=278 MUg/g creatinine. Anthropometric measurements were collected
      through 2012 (n = 1,017). Linear mixed effects regression estimated how baseline
      low and high-molecular weight phthalate concentrations related to changes in
      girls' body mass index (BMI), height, and waist circumference at ages 7-13 years.
      RESULTS: Low-molecular weight phthalates were positively associated with gains in
      BMI and waist circumference. Predicted differences in BMI and waist circumference
      between girls with high versus low concentrations of low-molecular weight
      phthalates increased from 0.56 (95% confidence interval [CI]: -0.02, 1.1) to 1.2
      kg/m (95% CI: 0.28, 2.1) and from 1.5 (95% CI: -0.38, 3.3) to 3.9 cm (95% CI:
      1.3, 6.5), respectively. High-molecular weight phthalates were negatively
      associated with height but only among girls who were normal weight at baseline
      (BMI <= 85th percentile). CONCLUSION: Phthalates, specifically low-molecular
      weight phthalates, have small but detectable associations with girls'
      anthropometric outcomes. Low-molecular weight phthalates showed stronger
      associations than other types of phthalates.

PMID- 27031040
TI  - Prelabor Cesarean Section and Risk of Childhood Type 1 Diabetes: A Nationwide
      Register-based Cohort Study.
AB  - BACKGROUND: Unfavorable conditions associated with cesarean section may influence
      the risk of type 1 diabetes in offspring, but results from studies are
      conflicting. We aimed to evaluate the association between prelabor cesarean
      section and risk of childhood type 1 diabetes. METHODS: A Danish nationwide
      cohort study followed all singletons born during 1982-2010. Four national
      registers provided information on mode of delivery, outcome, and confounders. The
      risk of childhood type 1 diabetes with onset before the age of 15 years was
      assessed by Cox regression. A total of 1,760,336 singletons contributed
      20,436,684 person-years, during which 4,400 were diagnosed with childhood type 1
      diabetes. RESULTS: The hazard ratio (HR) for childhood type 1 diabetes was
      increased in children delivered by prelabor cesarean section compared with
      vaginal delivery when adjusted for year of birth, parity, sex, parental age, and
      education and paternal type 1 diabetes status at childbirth (HR = 1.2; 95%
      confidence interval [CI] = 1.0, 1.3), but not after additional adjustment for
      maternal type 1 diabetes status at childbirth (HR = 1.1; 95% CI = 0.95, 1.2).
      Delivery by intrapartum cesarean section was not associated with childhood type 1
      diabetes. Paternal type 1 diabetes was a stronger risk factor for childhood type
      1 (HR = 12; 95% CI = 10, 14) than maternal type 1 diabetes (HR = 6.5; 95% CI =
      5.2, 8.0). CONCLUSIONS: Delivery by prelabor cesarean section was not associated
      with an increased risk of childhood type 1 diabetes in the offspring.

PMID- 27031041
TI  - Commentary: Can a Quasi-experimental Design Be a Better Idea than an Experimental
      One?

PMID- 27031042
TI  - Use of Calcium Channel Blockers and Risk of Breast Cancer: A Population-based
      Cohort Study.
AB  - BACKGROUND: Several observational studies have associated use of calcium channel
      blockers with an increased risk of breast cancer, but this association remains
      controversial. The objective of this study was to determine whether these drugs
      are associated with an increased risk of breast cancer overall, and to assess
      whether this risk varies with cumulative duration of use. METHODS: We identified
      a cohort of 273,152 women newly treated with antihypertensive drugs between 1
      January 1995 and 31 December 2009, followed until 31 December 2010, using the UK
      Clinical Practice Research Datalink. We treated calcium channel blocker use as a
      time-varying variable, and lagged exposure by 1 year for latency considerations
      and to minimize reverse causality. We used time-dependent Cox proportional
      hazards models to estimate adjusted hazard ratios with 95% confidence intervals
      of incident breast cancer associated with use of calcium channel blockers overall
      and by cumulative duration of use (<5, 5-10, and >=10 years). RESULTS: During
      1,567,104 person-years of follow-up, 4,520 women were newly diagnosed with breast
      cancer (incidence rate: 2.9 per 1,000 per year). Compared with use of other
      antihypertensive drugs, use of calcium channel blockers was not associated with
      increased risk of breast cancer overall (hazard ratio: 0.97, 95% confidence
      interval: 0.91, 1.03). Similarly, there was no evidence of a duration-response
      relationship in terms of cumulative duration of use (P trend = 0.26).
      CONCLUSIONS: The results of this large population-based study indicate that long
      term use of calcium channel blockers is not associated with an increased risk of
      breast cancer.

PMID- 27031043
TI  - External validity of Concealed Information Test experiment: Comparison of
      respiration, skin conductance, and heart rate between experimental and field card
      tests.
AB  - The Concealed Information Test (CIT) is a memory detection method based on an
      examinee's physiological responses to crime-relevant items (critical items) in
      comparison with crime-irrelevant items (noncritical items). I examined the
      external validity of CIT laboratory experiments by comparing respiratory speed
      (RS), skin conductance response (SCR), and heart rate (HR) between a laboratory
      experiment (n = 30) and a field test (n = 30) in a card test. A linear mixed
      models analysis showed that the critical items in both CIT contexts elicited CIT
      effects: RS repression, SCR increase, and HR deceleration. Additionally, the
      critical items in the field elicited a larger RS suppression than those in the
      laboratory; however, SCR and HR on the critical items showed no statistical
      differences between the laboratory and field CITs. Moreover, the tonic HRs in the
      field tests were higher than in the CIT experiments, but there were no
      significant correlations between the tonic HR and each CIT effect in RS, SCR, and
      HR. These results suggested that CIT detection efficiency was not affected by
      arousal levels and may imply that the CIT effects observed with RS, SCR, and HR
      in the CIT laboratory experiments has adequate external validity and can be
      generalized to the CIT field.

PMID- 27031044
TI  - Novel ESCRT functions in cell biology: spiraling out of control?
AB  - The endosomal sorting complex required for transport (ESCRT), originally
      identified for its role in endosomal protein sorting and biogenesis of
      multivesicular endosomes (MVEs), has proven to be a versatile machinery for
      involution and scission of narrow membrane invaginations filled with cytosol.
      Budding of enveloped viruses and cytokinetic abscission were early described
      functions for the ESCRT machinery, and recently a number of new ESCRT functions
      have emerged. These include cytokinetic abscission checkpoint control, plasma
      membrane repair, exovesicle release, quality control of nuclear pore complexes,
      neuron pruning, and sealing of the newly formed nuclear envelope. Here we review
      these novel ESCRT mechanisms and discuss similarities and differences between the
      various ESCRT-dependent activities.

PMID- 27031046
TI  - A novel TRIM family member, Trim69, regulates zebrafish development through p53
      mediated apoptosis.
AB  - Trim69 contains the hallmark domains of a tripartite motif (TRIM) protein,
      including a Ring-finger domain, B-box domain, and coiled-coil domain. Trim69 is
      structurally and evolutionarily conserved in zebrafish, mouse, rat, human, and
      chimpanzee. The role of this protein is unclear, however, so we investigated its
      function in zebrafish development. Trim69 is extensively expressed in zebrafish
      adults and developing embryos-particularly in the testis, brain, ovary, and heart
      and its expression decreases in a time- and stage-dependent manner. Loss of
      trim69 in zebrafish induces apoptosis and activates apoptosis-related processes;
      indeed, the tp53 pathway was up-regulated in response to the knockdown.
      Expression of human trim69 rescued the apoptotic phenotype, while overexpression
      of trim69 does not increase cellular apoptosis. Taken together, our results
      suggest that trim69 participates in tp53-mediated apoptosis during zebrafish
      development. Mol. Reprod. Dev. 83: 442-454, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27031045
TI  - A model for coordinating nuclear mechanics and membrane remodeling to support
      nuclear integrity.
AB  - A polymer network of intranuclear lamin filaments underlies the nuclear envelope
      and provides mechanical stability to the nucleus in metazoans. Recent work
      demonstrates that the expression of A-type lamins scales positively with the
      stiffness of the cellular environment, thereby coupling nuclear and extracellular
      mechanics. Using the spectrin-actin network at the erythrocyte plasma membrane as
      a model, we contemplate how the relative stiffness of the nuclear scaffold
      impinges on the growing number of interphase-specific nuclear envelope remodeling
      events, including recently discovered, nuclear envelope-specialized quality
      control mechanisms. We suggest that a stiffer lamina impedes these remodeling
      events, necessitating local lamina remodeling and/or concomitant scaling of the
      efficacy of membrane-remodeling machineries that act at the nuclear envelope.

PMID- 27031047
TI  - Kinematic gait patterns and their relationship to pain in mild-to-moderate hip
      osteoarthritis.
AB  - BACKGROUND: Mild-to-moderate hip osteoarthritis is often managed clinically in a
      non-surgical manner. Effective non-surgical management of this population
      requires characterizing the specific impairments within this group. To date, a
      complete description of all lower extremity kinematics in mild-to-moderate hip
      osteoarthritis patients has not been presented. The aim of the present study is
      to describe the lower extremity gait kinematics in mild-to-moderate hip
      osteoarthritis patients and explore the relationship between kinematics and pain.
      METHODS: 22 subjects with mild-to-moderate radiographic hip osteoarthritis
      (Kellgren-Lawrence grade 2-3) and 22 healthy age and BMI matched control subjects
      participated. Kinematic treadmill walking data were collected across all lower
      extremity joints. A two-way repeated measures analysis of variance estimated mean
      differences in gait kinematics between groups. Correlations between gait
      kinematics and pain were assessed using a Spearman correlation coefficient.
      FINDINGS: Hip osteoarthritis subjects hiked their unsupported hemi-pelvis 1.40
      degrees  (P<0.001) more than controls and tilted their pelvis 4.65 degrees  more
      anteriorly (P=0.01). Osteoarthritis subjects walked with 4.30 degrees  more peak
      hip abduction (P<0.001), 8.57 degrees  less peak hip extension (P<0.001), and
      10.54 degrees  more peak hip external rotation (P<0.001). Kinematics were related
      to pain in the ankle frontal plane only (r=-0.43, P<0.05). INTERPRETATION:
      Individuals with mild-to-moderate hip osteoarthritis demonstrate altered gait
      biomechanics not related to pain. These altered biomechanics may represent
      effective therapeutic targets by clinicians working with this population.
      Understanding the underlying patho-anatomic changes that lead to these
      biomechanical changes requires further investigation.

PMID- 27031048
TI  - Chloride Ion Mediated Synthesis of Metal/Semiconductor Hybrid Nanocrystals.
AB  - A synthetic route to prepare metal-semiconductor hybrid nanoparticles is
      presented, along with the possibility to tune the ratio of primary to secondary
      nucleation and the morphology of the semiconductor material grown on the metal
      nanoparticle seeds. Gold and cobalt-platinum nanoparticles are employed as metal
      seeds, on which CdS or CdSe is grown. Using transmission electron microscopy,
      absorption spectroscopy (UV-vis), and powder X-ray diffraction as
      characterization techniques, a significant influence of chloride ions on the type
      of nucleation (that is, secondary or primary nucleation) as well as on the shape
      of the resulting heterostructures is observed. Partially replacing the commonly
      used cadmium precursor CdO by varying amounts of CdCl2 opens access to rod-like,
      multiarmed, flower-like, and bullet-like structures. The results suggest that
      neither pure CdO nor pure CdCl2 as precursors but only a mixture of both make
      these structures obtainable. In this article, the influence of the chloride ion
      concentration during semiconductor growth on metal seeds is investigated in
      depth. The morphology of the resulting heterostructures is characterized
      carefully, and a growth mechanism is suggested. Furthermore, it is shown that
      this synthetic approach can be transferred to seeds of various metals such as
      platinum, gold, and cobalt platinum.

PMID- 27031049
TI  - The INR is only one side of the coagulation cascade: time to watch the clot.

PMID- 27031050
TI  - Embelin inhibits proliferation, induces apoptosis and alters gene expression
      profiles in breast cancer cells.
AB  - PURPOSE: To investigate effect of embelin on proliferation, apoptosis and gene
      expression profile changes in breast cancer cells. METHODS: Cell viability was
      determined by MTT assay and apoptosis assayed using flow cytometry. Differential
      expression of 84 genes commonly involved in breast cancer carcinogenesis was
      assessed by real-time PCR using the Human Breast Cancer RT(2) Profiler PCR Array.
      RESULTS: MCF-7 and MDA-MB-231 cells were treated with embelin (0-25MUM) for 24
      and 96h. Embelin exhibited time and dose dependence in both cell lines and was
      more potent in inhibiting MDA-MB-231 cell proliferation compared to MCF-7 cells.
      IC50 for embelin in MDA-MB-231 cells was ~4.45MUM and 3.28MUM at 24h and 96h,
      respectively. In contrast, IC50 for embelin in MCF-7 cells was ~6.04MUM and
      4.51MUM at 24h and 96h, respectively. Embelin (50MUM) induced apoptosis and
      activated caspase 3 activity in both cell lines when exposed for 72h. Treatment
      of MDA-MB-231 cells with embelin (10MUM) for 24h resulted in significant
      differential expression of 27 genes commonly involved in breast cancer
      carcinogenesis. CONCLUSIONS: Our findings show that embelin inhibits cell
      proliferation, induces apoptosis and alters expression of breast cancer focused
      genes in MCF-7 and MDA-MB-231 cells. Based on RT(2)-PCR array analysis, embelin
      down-regulated expression of pivotal oncogenes. This knowledge could be
      beneficial in the development of effective embelin-based therapies for treating
      breast cancer.

PMID- 27031051
TI  - Involvement of c-Myc-mediated transient receptor potential melastatin 8
      expression in oxaliplatin-induced cold allodynia in mice.
AB  - BACKGROUND: Oxaliplatin, a platinum-based chemotherapeutic agent, induces acute
      cold allodynia and dysesthesia. Cold-sensitive transient receptor potential
      channels (TRPM8 and TRPA1) have been implicated as candidates to mediate
      oxaliplatin-induced cold allodynia and hyperalgesia, but precise roles of these
      channels remain unclear. In this study, we investigated the role of TRPM8 in
      oxaliplatin-induced cold allodynia. METHODS: Oxaliplatin was injected
      intraperitoneally in mice. Cold allodynia was evaluated by the acetone test.
      Expression levels of TRPM8 mRNA and protein were measured using reverse
      transcription-polymerase chain reaction and Western blotting, respectively.
      RESULTS: Oxaliplatin-induced cold allodynia was alleviated by the TRPM8 blockers
      N-(2-aminoethyl)-N-[4-(benzyloxy)-3-methoxybenzyl]-N'-(1S)-1-(phenyl) ethyl] urea
      and TC-I 2014. Oxaliplatin increased the expression levels of TRPM8 mRNA and
      protein in the dorsal root ganglia and plantar skin, respectively. Prophylactic
      administration of the c-Myc inhibitor 10058-F4 prevented cold allodynia and the
      increase of TRPM8 mRNA after oxaliplatin injection. CONCLUSION: These results
      suggest that oxaliplatin induces cold allodynia through the increase of c-Myc
      mediated TRPM8 expression in primary sensory neurons.

PMID- 27031052
TI  - Prazosin-stimulated release of hepatic triacylglyceride lipase from primary
      cultured rat hepatocytes is involved in the regulation of cAMP-dependent protein
      kinase through activation of the Ca(2+)/calmodulin-dependent protein kinase-II.
AB  - BACKGROUND: Prazosin is an alpha1 adrenoceptor antagonist used in pharmacotherapy
      for the treatment of hypertension. Prazosin alters lipid metabolism in vivo, but
      the involved mechanism is not fully understood. In this study, we investigated
      the mechanism underlying the alteration of lipid metabolism. We show that the
      prazosin-stimulated release of hepatic triacylglyceride lipase (HTGL) from
      primary cultured rat hepatocytes involved Ca(2+)/calmodulin-dependent protein
      kinase II (CaMK-II) activation. METHODS: Primary cultured rat hepatocytes were
      incubated with prazosin and other agents. The hepatocytes were used in the CaMK
      II and protein kinase A (PKA) activity assay. The supernatant was used in the
      HTGL activity assay and western blotting. RESULTS: Prazosin-stimulated HTGL
      release was suppressed by the inositol triphosphate receptor inhibitor
      xestospongin C and by the calmodulin inhibitor trifluoperazine but not by the
      protein kinase C inhibitor chelerythrine chloride or a diacylglycerol kinase
      inhibitor (R59949). Furthermore, the calmodulin-dependent protein kinase II (CaMK
      II) activity in prazosin-treated hepatocytes increased in a time- and dose
      dependent manner. The cAMP-dependent PKA activity of prazosin-stimulated
      hepatocytes was suppressed by a phospholipase C (PLC) inhibitor (U-73122),
      trifluoperazine, and a CaMK-II inhibitor (KN-93). CONCLUSIONS: These results
      suggested that prazosin-stimulated HTGL release from hepatocytes was caused by
      activation of PKA associated with stimulation of CaMK-II activity through a
      signal cascade from PLC.

PMID- 27031053
TI  - Feeding during Blood Transfusions and the Association with Necrotizing
      Enterocolitis.
AB  - Objective The aim of this study was to determine whether very low-birth-weight
      (VLBW) infants who had feedings withheld during all blood transfusions had a
      lower incidence of necrotizing enterocolitis (NEC) compared with infants who were
      fed during transfusions. Study Design A retrospective chart review over a 3-year
      period in a level-3 neonatal intensive care unit was conducted. A total of 108
      inborn VLBW infants (weight range: 500-1,500 g) who had received a transfusion
      before 36 weeks were reviewed. Diagnosis of NEC (>= Bell stage II), demographics,
      feeds, transfusions, outcomes, and variables associated with NEC were collected.
      Results The percentage of NEC cases was lower in infants who had feeds withheld
      during transfusions: 5/64 (7.8%) compared with 16/116 (13.8%) infants who were
      fed during transfusions. While potentially clinically important (6% absolute
      difference), this difference was not statistically significant (p = 0.33 by two
      tailed Fisher exact test). Conclusions No significant decrease in the incidence
      of NEC was found when feeds were withheld during blood transfusions. Holding
      feeds during transfusions is not without consequences such as the need for
      intravenous access, additional fluids, and the disruption of optimum nutrition.
      Further studies are needed to establish the relationship between blood
      transfusions, feeds, and NEC.

PMID- 27031054
TI  - Maternal Mortality from Obstructed Labor: A MANDATE Analysis of the Ability of
      Technology to Save Lives in Sub-Saharan Africa.
AB  - Objective The aim of the study is to evaluate clinical interventions to
      significantly reduce maternal mortality from prolonged labor, obstructed labor,
      and prolonged obstructed labor (PL/OL/POL) in sub-Saharan Africa (SSA). Methods A
      mathematical model-Maternal and Neonatal Directed Assessment of Technology
      ("MANDATE")-was created for SSA with estimated prevalence for PL/OL/POL and case
      fatality rates from hemorrhage, infection, and uterine rupture. Based on a
      literature review and expert opinion, the model was populated with estimated
      likelihoods of the current healthcare system ability to diagnose, transfer, and
      treat women with these conditions. Impact on maternal mortality of improved
      diagnosis, transfer, and delivery to relieve PL/OL/POL was assessed. Results
      Without current technologies, the model estimated 8,464 maternal deaths annually
      in SSA from these conditions. Imputing current diagnosis, transfer, and treatment
      of PL/OL/POL, an estimated 7,033 maternal deaths occur annually from these
      complications. With improved PL/OL/POL diagnosis and improved transfer, 1,700 and
      740 lives could be saved, respectively. Improved diagnosis, transfer, and
      treatment for PL/OL/POL reduce the mortality rate to 864 maternal deaths
      annually, saving 6,169 lives. If improved transfusion and antibiotic use were
      added, only 507 women per year would die from PL/OL/POL in SSA. Conclusion In
      SSA, increasing diagnostics, transfer to higher care, and operative delivery
      could substantially reduce maternal mortality from PL/OL/POL. Synopsis A
      computerized model of obstructed labor in SSA was created to explore the
      interventions necessary to reduce maternal mortality from this condition.

PMID- 27031055
TI  - Foley Catheter or Oral Misoprostol for Induction of Labor in Women with Term
      Premature Rupture of Membranes: A Randomized Multicenter Trial.
AB  - Objectives To compare the Foley catheter and misoprostol for induction of labor
      in term women with premature rupture of membranes. Study Design A randomized
      controlled trial was performed in three university hospitals in Finland between
      March 2012 and September 2014. A total of 202 term women with ruptured membranes
      >18 hours, singleton pregnancies in cephalic presentation, unfavorable cervix,
      and no prior cesarean section were enrolled. Participants were randomly allocated
      to induction of labor by Foley catheter or oral misoprostol in a 1:1 ratio. All
      women received prophylactic antibiotics. The main outcomes were cesarean section
      and maternal and neonatal infections. Results Labor induction by Foley catheter
      or misoprostol showed no difference in cesarean delivery rates (23.6 vs. 18.2%;
      odds ratio [OR], 1.39; 95% confidence interval [CI], 0.69-2.82; p = 0.36),
      maternal intrapartum infections (2.2 vs. 2%; OR, 1.12; 95% CI, 0.15-8.9; p =
      1.00), postpartum infections (1.1 vs. 2.0%; OR, 0.55; 95% CI, 0.05-6.18; p =
      1.00), or neonatal infections (1.1 vs. 5.1%; OR, 0.21; 95% CI, 0.24-1.87; p =
      0.22). The total time from induction to delivery was similar (1,311 vs. 1,435
      minutes; p = 0.31) in the two groups. Conclusions Foley catheter or misoprostol
      can both be used for induction of labor in women with term premature rupture of
      membranes.

PMID- 27031056
TI  - Pre-eclampsia and Cardiovascular Disease Risk Assessment in Women.
AB  - The underlying contributors of many cardiovascular events are often present
      decades before the onset of clinical symptoms, and the presence of risk factors
      in early life significantly influences risk of premature cardiovascular disease
      (CVD). The considerable burden of CVD in women and on health care resources
      necessitates an emphasis on prevention and early risk screening in women, before
      the development of the disease itself. The 2011 update to the American Heart
      Association's Effectiveness-Based Guidelines for the prevention of CVD
      acknowledges the contribution of the common pregnancy-related medical
      complications to a woman's cardiovascular risk, identifying pre-eclampsia (PE),
      gestational hypertension, and gestational diabetes mellitus as risk factors for
      heart disease and stroke. The aims of this review are to examine risk factors in
      young women and their role in the development of premature CVD, with particular
      attention paid to PE as a marker of a woman's cardiovascular risk. Current
      screening practices will be discussed, as will their influences on identifying
      and reducing cardiovascular risk and subsequent disease in younger women.

PMID- 27031057
TI  - New insight on the underdrawing of 16th Flemish-Portuguese easel paintings by
      combined surface analysis and microanalytical techniques.
AB  - This paper focusses on the study of the underdrawings of 16th century easel
      paintings attributed to the workshop of the Portuguese-Flemish Master Frei
      Carlos. This investigation encompasses multidisciplinary research that relates
      the results of surface exams (infrared reflectography, standard light photography
      and infrared photography) with analytical investigations. The surface analysis of
      Frei Carlos' underdrawings by infrared reflectography has shown heterogeneous
      work, revealing two different situations: (1) an abundant and expressive
      underdrawing, revealing a Flemish influence and (2) a simple and outlined
      underdrawing. This preliminary research raised an important question related to
      this Portuguese-Flemish workshop and to the analytical approach: Is the
      underdrawing's heterogeneity, as observed in the reflectograms, related to
      different artists or is this rather an effect that is produced due to the use of
      different materials in the underdrawing's execution? Consequently, if different
      materials were used, how can we have access to the hidden underdrawings? In order
      to understand the reasons for this dissemblance, chemical analysis of micro
      samples collected in underdrawing areas and representing both situations were
      carried out by optical microscopy, micro Fourier transform infrared spectroscopy
      (MU-FTIR), scanning electron microscopy coupled with energy dispersive X-ray
      spectrometry (SEM-EDX) and micro-Raman spectroscopy (MU-Raman). Taking into
      account the different possibilities and practical and theoretical limitations of
      surface and punctual examinations in the study of easel painting underdrawings,
      the methodology of research was adjusted, sometimes resulting in a re-analysis of
      experimental results. This research shows the importance of combining
      multispectral surface exams and chemical analysis in the understanding of the
      artistic creative processes of 16th century easel paintings. 

PMID- 27031058
TI  - Bulk Metallic Glasses for Implantable Medical Devices and Surgical Tools.
AB  - With increasing knowledge of the materials science of bulk metallic glasses
      (BMGs) and improvements in their properties and processing, they have started to
      become candidate materials for biomedical devices. A dichotomy in the types of
      medical applications has also emerged, in which some families of BMGs are being
      developed for permanent devices whilst another family - of Mg-based alloys - is
      showing promise in bioabsorbable implants. The current status of these
      metallurgical and technological developments is summarized. 

PMID- 27031059
TI  - Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an
      extended family.
AB  - BACKGROUND: The aim of this study was to describe the pattern of inheritance and
      the clinical features in a large family with Waardenburg syndrome type I (WS1),
      detailing the dental abnormalities and screening for PAX3 mutations. MATERIAL AND
      METHODS: To characterize the pattern of inheritance and clinical features, 29
      family members were evaluated by dermatologic, ophthalmologic,
      otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3
      gene was performed. RESULTS: The pedigree of the family,including the last four
      generations, was constructed and revealed non-consanguineous marriages. Out of 29
      descendants, 16 family members showed features of WS1, with 9 members showing two
      major criteria indicative of WS1. Five patients showed white forelock and iris
      hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation.
      Two patients had hearing loss. Dental abnormalities were identified in three
      family members, including dental agenesis, conical teeth and taurodontism.
      Sequencing analysis failed to identify mutations in the PAX3 gene. CONCLUSIONS:
      These results confirm that WS1 was transmitted in this family in an autosomal
      dominant pattern with variable expressivity and high penetrance. The presence of
      dental manifestations, especially tooth agenesis and conical teeth which resulted
      in considerable aesthetic impact on affected individuals was a major clinical
      feature. CLINICAL RELEVANCE: This article reveals the presence of well-defined
      dental changes associated with WS1 and tries to establish a possible association
      between these two entities showing a new spectrum of WS1.

PMID- 27031060
TI  - The development of proliferative verrucous leukoplakia in oral lichen planus. A
      preliminary study.
AB  - BACKGROUND: Was to describe 14 cases of a proliferative verrucous leukoplakia as
      a clinical evolution of oral lichen planus. MATERIAL AND METHODS: The clinical
      and histopathological characteristics of 14 cases of OLP that progress towards a
      plaque-like and verrucous form were indicated, with monitoring over a period of
      six to 24.3 years. RESULTS: The female/male ratio was 11/3, (78.6 and 21.4%). The
      mean age when the first biopsy was undertaken was 56.4 years old. None of the
      patients smoked during the study. As bilateral reticular was clinically
      diagnostic criterion, the second most frequent clinical form was the plaque form
      (n=10; 71.4%), followed by the atrophic (n=6; 42.8%), and erosive forms (n=4;
      28.5%). Clinically it spread towards attached gingival mucosa and the hard
      palate. In the histopathologic study, there were a predominance of hyperkeratosis
      and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous
      cell carcinoma, and one patient developed two verrucous carcinoma. CONCLUSIONS:
      Further research is needed to demonstrate if proliferative multifocal oral lichen
      planus and proliferative multifocal oral leukoplakia are the same disorder but
      have different behaviour of malignancy for reasons of origin.

PMID- 27031061
TI  - Treatment of xerostomia and hyposalivation in the elderly: A systematic review.
AB  - BACKGROUND: Therapeutic strategies for xerostomia, regardless of etiology, have
      so far not had definitive or clearly effective results. OBJECTIVES: To
      systematically revise the latest scientific evidence available regarding the
      treatment of dry mouth, regardless of the cause of the problem. MATERIAL AND
      METHODS: The literature search was conducted in March 2015, using the Medline and
      Embase databases. The "Clinical Trial", from 2006 to March 2015, was carried out
      in English and only on human cases. The draft of the systematic review and
      assessment of the methodological quality of the trials was carried out following
      the criteria of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) and the "Oxford Quality Scale". RESULTS: Finally, a total of 26 trials
      were identified that met the previously defined selection and quality criteria;
      14 related to drug treatments for dry mouth, 10 with non-pharmacological
      treatment and 2 with alternative treatments. CONCLUSIONS: Pilocarpine continues
      to be the best performing sialogogue drug for subjects with xerostomia due to
      radiation on head and neck cancer or diseases such as Sjogren's Syndrome. For
      patients with dry mouth caused solely by medication, there are some positive
      indications from the use of malic acid, along with other elements that counteract
      the harmful effect on dental enamel. In general, lubrication of oral mucous
      membrane reduces the symptoms, although the effects are short-lived.

PMID- 27031062
TI  - Alterations in 18F-FDG accumulation into neck-related muscles after neck
      dissection for patients with oral cancers.
AB  - BACKGROUND: 18F-fluoro-2-deoxy-D-glucose (18F-FDG) accumulations are commonly
      seen in the neck-related muscles of the surgical and non-surgical sides after
      surgery with neck dissection (ND) for oral cancers, which leads to radiologists
      having difficulty in diagnosing the lesions. To examine the alterations in 18F
      FDG accumulation in neck-related muscles of patients after ND for oral cancer.
      MATERIAL AND METHODS: 18F-FDG accumulations on positron emission tomography (PET)
      computed tomography (CT) in neck-related muscles were retrospectively analyzed
      after surgical dissection of cervical lymph nodes in oral cancers. RESULTS:
      According to the extent of ND of cervical lymph nodes, the rate of patients with
      18F-FDG-PET-positive areas increased in the trapezius, sternocleidomastoid, and
      posterior neck muscles of the surgical and/or non-surgical sides. In addition,
      SUVmax of 18F-FDG-PET-positive areas in the trapezius and sternocleidomastoid
      muscles were increased according to the extent of the ND. CONCLUSIONS: In
      evaluating 18F-FDG accumulations after ND for oral cancers, we should pay
      attention to the 18F-FDG distributions in neck-related muscles including the non
      surgical side as false-positive findings.

PMID- 27031063
TI  - Rapid maxillary expansion and obstructive sleep apnea: A review and meta
      analysis.
AB  - BACKGROUND: OSAS during childhood leads to significant physical and
      neuropsychomotor impairment. Thus, it needs to be recognized and treated early in
      order to avoid or attenuate the chronic problems associated with OSAS, which are
      deleterious to a child's development. Adenotonsillectomy and, in select cases,
      continuous positive airwaypressure (CPAP) have been the preferred treatments for
      OSAS in children, and yet they are ineffective at fully ameliorating the disease.
      Minimally invasive treatments have recently been proposed, comprising intra-oral
      and extra-oral devices as well as speech therapy. Objetive: to conduct a meta
      analysis on studies from around the world that used rapid maxillary expansion
      (RME) to treat OSAS in children. MATERIAL AND METHODS: We performed a meta
      analysis of studies using RME for OSA treatment in children. A literature survey
      was conductedusing PubMed and Medline for English articles published up to
      December 2014 with the following descriptors: SleepApnea, Obstructive, Children,
      Treatment, Orthodontic, Othopaedic, Maxillaryexpansion. Studies were included in
      the meta-analysisif they were case-controlled studies, randomized, and involved
      non-syndromic children aged 0 to 12years old diagnosed with OSA by the
      polysomnography apnea-hypopnea index (AHI) before and after the intervention,
      submitted RME only. RESULTS: In all, 10 articles conformed to the inclusion
      criteria and were included in this meta-analysis. The total sample size across
      all these articles was 215 children, having a mean age of 6.7 years,of
      whom58.6%were male. The mean AHI during the follow-up was -6.86 (p <0.0001).
      CONCLUSIONS: We concluded that rapid maxillary expansion (RME) in children with
      OSAS appears to be an effective treatment for this syndrome. Further randomized
      clinical studies are needed to determine the effectiveness of RME in adults.

PMID- 27031064
TI  - Coronectomy of impacted mandibular third molars: A meta-analysis and systematic
      review of the literature.
AB  - BACKGROUND: Coronectomy is an alternative to complete removal of an impacted
      mandibular third molar. Most authors have recommended coronectomy to prevent
      damage to the inferior alveolar nerve during surgical extraction of lower third
      molars. The present study offers a systematic review and metaanalysis of the
      coronectomy technique. MATERIAL AND METHODS: A systematic review and meta
      analysis was performed based on a PubMed and Cochrane databases search for
      articles published from 2014 and involving coronectomy of mandibular third molars
      located near the inferior alveolar nerve canal, with a minimum of 10 cases and a
      minimum follow-up period of 6 months. After application of the inclusion and
      exclusion criteria, a total of 12 articles were included in the study. RESULTS
      AND DISCUSSION: Coronectomy results in significantly lesser loss of sensitivity
      of the inferior alveolar nerve and prevents the occurrence of dry socket. No
      statistically significant differences were observed in the incidence of pain and
      infection between coronectomy and complete surgical extraction. After
      coronectomy, the remaining tooth fragment migrates an average of 2 mm within two
      years. CONCLUSIONS: Coronectomy is indicated when the mandibular third molar is
      in contact with the inferior alveolar nerve and complete removal of the tooth may
      cause nerve damage.

PMID- 27031065
TI  - Serum zinc levels in 368 patients with oral mucosal diseases: A preliminary
      study.
AB  - BACKGROUND: The aim of this study was to assess the serum zinc levels in patients
      with common oral mucosal diseases by comparing these to healthy controls.
      MATERIAL AND METHODS: A total of 368 patients, which consisted of 156 recurrent
      aphthous stomatitis (RAS) patients, 57 oral lichen planus (OLP) patients, 55
      burning mouth syndrome (BMS) patients, 54 atrophic glossitis (AG) patients, 46
      xerostomia patients, and 115 sex-and age-matched healthy control subjects were
      enrolled in this study. Serum zinc levels were measured in all participants.
      Statistical analysis was performed using a one-way ANOVA, t-test, and Chi-square
      test. RESULTS: The mean serum zinc level in the healthy control group was
      significantly higher than the levels of all other groups (p < 0.001). No
      individual in the healthy control group had a serum zinc level less than the
      minimum normal value. However, up to 24.7% (13/54) of patients with AG presented
      with zinc deficiency, while 21.2% (33/156) of patients with RAS, 16.4% (9/55) of
      patients with BMS, 15.2% (7/46) of patients with xerostomia, and 14.0% (8/57) of
      patients with OLP were zinc deficient. Altogether, the zinc deficiency rate was
      19.02% (70/368) in the oral mucosal diseases (OMD) group (all patients with OMD).
      The difference between the OMD and healthy control group was significant (p
      <0.001). Gender differences in serum zinc levels were also present, although not
      statistically significant. CONCLUSIONS: Zinc deficiency may be involved in the
      pathogenesis of common oral mucosal diseases. Zinc supplementation may be a
      useful treatment for oral mucosal diseases, but this requires further
      investigation; the optimal serum level of zinc, for the prevention and treatment
      of oral mucosal diseases, remains to be determined.

PMID- 27031066
TI  - Association of Toll-like receptors 2, 3, and 4 genes polymorphisms with
      periapical pathosis risk.
AB  - BACKGROUND: The aim of this study was to investigate the role of gene variations
      of Toll-like receptors (TLR) 2, 3, and 4 on genetic susceptibility to periapical
      pathosis. MATERIAL AND METHODS: One hundred patients were included in the study
      and divided into two groups as follows; Control Group (n=50) that have root canal
      treatment and no periapical lesion, Patient Group (n=50) that have root canal
      treatment and periapical lesion. TLR2 Arg753Gln, TLR3 (c.1377C/T) and TLR4
      Asp299Gly and Thr399Ile polymorphisms were genotyped by using PCR-RFLP.
      Genotypical analysis of control and patient groups were investigated to disclose
      whether there is any association between periapical lesions and gene variations.
      RESULTS: There are no significant statistical differences between control and
      patient groups according to TLR 2 and 4 gene sequence. On the contrary, CC allele
      detected 74% for TLR 3 in patient group, and this difference was found to be
      statistically significant (p < 0.005). CONCLUSIONS: According to these results,
      it can be suggested that patients with Toll-like receptor 3 gene polymorphisms
      could be susceptible to periapical pathosis.

PMID- 27031067
TI  - Accelerating orthodontic tooth movement: A new, minimally-invasive corticotomy
      technique using a 3D-printed surgical template.
AB  - BACKGROUND: A reduction in orthodontic treatment time can be attained using
      corticotomies. The aggressive nature of corticotomy due to the elevation of muco
      periosteal flaps and to the duration of the surgery raised reluctance for its
      employ among patients and dental community. This study aims to provide detailed
      information on the design and manufacture of a 3D-printed CAD-CAM (computer-aided
      design and computer-aided manufacturing) surgical guide which can aid the
      clinician in achieving a minimally-invasive, flapless corticotomy. MATERIAL AND
      METHODS: An impression of dental arches was created; the models were digitally
      acquired using a 3D scanner and saved as STereoLithography ( STL ) files. The
      patient underwent cone beam computed tomography (CBCT): images of jaws and teeth
      were transformed into 3D models and saved as an STL file. An acrylic template
      with the design of a surgical guide was manufactured and scanned. The STLs of
      jaws, scanned casts, and acrylic templates were matched. 3D modeling software
      allowed the view of the 3D models from different perspectives and planes with
      perfect rendering. The 3D model of the acrylic template was transformed into a
      surgical guide with slots designed to guide, at first, a scalpel blade and then a
      piezoelectric cutting insert. The 3D STL model of the surgical guide was printed.
      RESULTS: This procedure allowed the manufacturing of a 3D-printed CAD/CAM
      surgical guide, which overcomes the disadvantages of the corticotomy, removing
      the need for flap elevation. No discomfort, early surgical complications or
      unexpected events were observed. CONCLUSIONS: The effectiveness of this minimally
      invasive surgical technique can offer the clinician a valid alternative to other
      methods currently in use.

PMID- 27031068
TI  - Premedication with midazolam in intellectually disabled dental patients:
      intramuscular or oral administration? A retrospective study.
AB  - BACKGROUND: The use of midazolam for dental care in patients with intellectual
      disability is poorly documented. The purpose of this study was to determine which
      method of premedication is more effective for these patients, 0.15 mg/kg of
      intramuscular midazolam or 0.3 mg/kg of oral midazolam. MATERIAL AND METHODS:
      This study was designed and implemented as a non-randomized retrospective study.
      The study population was composed of patients with intellectual disability who
      required dental treatment under ambulatory general anesthesia from August 2009
      through April 2013. Patients were administered 0.15 mg/kg of midazolam
      intramuscularly (Group IM) or 0.3 mg/kg orally (Group PO). The predictor variable
      was the method of midazolam administration. The outcome variables measured were
      Observer's Assessment of Alertness/ Sedation (OAA/S) Scale scores, the level of
      cooperation when entering the operation room and for venous cannulation, post
      anesthetic agitation and recovery time. RESULTS: Midazolam was administered
      intramuscularly in 23 patients and orally in 21 patients. More patients were
      successfully sedated with no resistance behavior during venous cannulation in
      Group PO than in Group IM (p=0.034). There were no differences in demographic
      data and other variables between the groups. CONCLUSIONS: The results of this
      study suggest that oral premedication with 0.3 mg/kg of midazolam is more
      effective than 0.15 mg/kg of midazolam administered intramuscularly, in terms of
      patient resistance to venous cannulation. If both oral and intramuscular routes
      of midazolam are acceptable in intellectually disabled patients, the oral route
      is recommended.

PMID- 27031069
TI  - Wearing complete dental prostheses - Effects on perioral morphology.
AB  - BACKGROUND: To adequately perform rehabilitation of edentulous patients by a
      complete removable dental prosthesis (CRDP) is from basic interest to dentists to
      understand the morphologic changes caused by re-establishment of a physiologic
      jaw relationship. Anthropometric analyses of standardized frontal view and
      profile photographs may help elucidate such changes. MATERIAL AND METHODS:
      Photographs of 31 edentulous patients were compared in relaxed lip closure and
      after insertion of a CRDP in stable occlusion. 2232 anthropometric distances were
      raised. Eighteen anthropometric indices reflecting the perioral morphology and
      its integration in the vertical facial harmony were investigated. RESULTS: The
      intercanthal - mouth width index (p>.001), medial - lateral cutaneous upper lip
      height index (p=.007), lower vermilion contour index (p=.022), vermilion - total
      upper lip height index (p=.018), cutaneous - total upper lip height index
      (p=.023), upper lip - nose height index (p=.001), nose - upper face height index
      (p=.002), chin - mandible height index (p=.013), upper lip - mandible height
      index (p=.045), nose - lower face height index (p=.018), and nose - face height
      index (p=.029) showed significant pre- to post-treatment changes. CONCLUSIONS:
      The investigated anthropometric indices presented reproducible results related to
      an increase in occlusal vertical dimension. Their application may be helpful in
      assessment, planning, and explanation of morphologic effects of CRDPs on the
      perioral and overall facial morphology, which may helps to improve the aesthetic
      outcome.

PMID- 27031070
TI  - Longterm quality of life after oncologic surgery and microvascular free flap
      reconstruction in patients with oral squamous cell carcinoma.
AB  - BACKGROUND: Quality of life (QoL) has become increasingly important in cancer
      treatment. It refers to the patient's perception of the effects of the disease
      and therapy, and their impact on daily functioning and general feeling of well
      being. MATERIAL AND METHODS: In this prospective study, a total of 100 patients
      treated at our institution, completed the European Organization for Research and
      Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific EORTC QLQ
      H&N35 module. The questionnaires were distributed to the patients between 12 and
      60 months postoperatively. RESULTS: Global QoL score was 58.3 deterioration and
      mean score for functioning scale was 76.7. Fatigue (28.7 +/- 26.1), followed by
      financial problems (27.7 +/- 33.5), insomnia (26.7 +/- 34.5) and pain (26.3 +/-
      29.9) had highest symptom score on QLQ-C30. Fatigue (r=-0.488), insomnia (r=
      0.416) and pain (r =-0.448) showed highest value for significantly negative
      correlation to global QoL. In the H&N35 module, restriction of mouth opening
      (43.3 +/- 38.6), dry mouth (40.7 +/- 36.9), sticky saliva (37.3 +/- 37.1) and
      eating in public (33.8 +/- 31.9) were the four worst symptoms. Swallowing problem
      (r=-0.438), eating in public (r=-0.420) and persistent severe speech (r=-0.398)
      ranked as the three worst symptoms with highest value for significantly negative
      correlation to global QoL. CONCLUSIONS: Longterm QoL after oncologic surgery and
      microvascular free flap reconstruction in patients with oral cancer is
      satisfactory. Measurung QoL should be considered as part of the evaluation of
      cancer treatment.

PMID- 27031071
TI  - Comparative study between two different staging systems (AJCC TNM VS
      BALLANTYNE'S) for mucosal melanomas of the Head & Neck.
AB  - BACKGROUND: Mucosal melanoma (MM) of head and neck (H&N) is a rare entity with a
      quite poor prognosis. Ballantyne's staging system has been commonly used since
      1970. In the 7th edition of the AJCC Staging Manual a new chapter for the staging
      of TNM Classification system for mucosal melanoma (MM) of the head and neck (H&N)
      has been introduced to reflect the particularly aggressive biological behavior of
      this neoplasm. The aim of this study was to analyze and compare among
      Ballantyne's staging system vs TNM H&N in terms of overall survival (OS) and
      disease-free survival (DFS) in a consecutive population of patients with MM in a
      cancer centre. MATERIAL AND METHODS: Descriptive analysis of demographic,
      clinical and pathological variables of MM of the Head & Neck were performed. We
      compared the survival curves for both systems according to the Kaplan-Meier
      method using the Log-rank test. RESULTS: An up-staging migration effect from
      Ballantyne's localized disease to moderate-ly and very advanced disease according
      to AJCC staging system. The 5-year DFS and OS for Ballantyne's Localized Disease
      and AJCC Stage III were 31% and 36% vs. 47% and 50%, respectively. For
      locoregional disease the 5-year DFS / OS were 5% / 10% for Ballantyne's system
      vs. 13.8% / 17.8% and 0 / 0% for AJCC Stages IVA and IVB, respectively.
      CONCLUSIONS: In this series, the TNM staging system for MM of the H&N predicted
      the prognosis of the disease when comparing with Ballantyne's system.

PMID- 27031072
TI  - Aesthetic perception of single implants placed in the anterior zone. A cross
      sectional study.
AB  - BACKGROUND: Several aesthetic indexes have been described to assess implant
      aesthetics. The aim of this study was to compare the aesthetic assessment made by
      dental professionals and students of single-tooth implants placed in the upper
      incisors. MATERIALS AND METHODS: A cross-sectional survey study using a
      subjective questionnaire to assess the aesthetics in 3 implant supported single
      tooth cases in the anterior maxilla was performed. The interviewed subjects were
      divided into 4 groups: dentist with experience in implant treatment, dentists
      without experience in implants and 3rd and 5th year dental students. The
      questionnaire consisted of 2 visual analogue scales (VAS) to evaluate aesthetics,
      the pink esthetic score (PES), the white esthetic score (WES) and the simplified
      papilla index (PI). RESULTS: One-hundred dentists and one-hundred dental students
      filled the aesthetic assessment questionnaire. The results showed that the
      subjects were more critical than reference values, specially concerning
      prosthetic issues. The differences between groups were more obvious in the case
      with the best result. On the other hand, few differences were detected in the
      remaining cases. Regarding soft tissue and crown features, experienced dentists
      in implant dentistry were the most demanding. Cronbach's Alpha showed values >=
      0,8 in the questionnaire in every case, which indicates an adequate reliability.
      CONCLUSIONS: Dentists and dental students have different opinions when assessing
      aesthetics of single tooth implant supported cases. Experience and area of
      expertise seem to influence the evaluation of aesthetics in the anterior region.

PMID- 27031073
TI  - The role of angiogenesis in implant dentistry part I: Review of titanium alloys,
      surface characteristics and treatments.
AB  - BACKGROUND: Angiogenesis plays an important role in osseointegration process by
      contributing to inflammatory and regenerative phases of surrounding alveolar
      bone. The present review evaluated the effect of titanium alloys and their
      surface characteristics including: surface topography (macro, micro, and nano),
      surface wettability/energy, surface hydrophilicity or hydrophobicity, surface
      charge, and surface treatments of dental implants on angiogenesis events, which
      occur during osseointegration period. MATERIAL AND METHODS: An electronic search
      was performed in PubMed, MEDLINE, and EMBASE databases via OVID using the
      keywords mentioned in the PubMed and MeSH headings regarding the role of
      angiogenesis in implant dentistry from January 2000-April 2014. RESULTS: Of the
      2,691 articles identified in our initial search results, only 30 met the
      inclusion criteria set for this review. The hydrophilicity and topography of
      dental implants are the most important and effective surface characteristics in
      angiogenesis and osteogenesis processes. The surface treatments or modifications
      of dental implants are mainly directed through the enhancement of biological
      activity and functionalization in order to promote osteogenesis and angiogenesis,
      and accelerate the osseointegration procedure. CONCLUSIONS: Angiogenesis is of
      great importance in implant dentistry in a manner that most of the surface
      characteristics and treatments of dental implants are directed toward creating a
      more pro-angiogenic surface on dental implants. A number of studies discussed the
      effect of titanium alloys, dental implant surface characteristic and treatments
      on agiogenesis process. However, clinical trials and in-vivo studies delineating
      the mechanisms of dental implants, and their surface characteristics or
      treatments, action in angiogenesis processes are lagging.

PMID- 27031075
TI  - The effect of swinging the arms on muscle activation and production of leg force
      during ski skating at different skiing speeds.
AB  - The study investigated the effects of arm swing during leg push-off in V2
      alternate/G4 skating on neuromuscular activation and force production by the leg
      muscles. Nine skilled cross-country skiers performed V2-alternate skating without
      poles at moderate, high, and maximal speeds, both with free (SWING) and
      restricted arm swing (NOSWING). Maximal speed was 5% greater in SWING (P<0.01),
      while neuromuscular activation and produced forces did not differ between
      techniques. At both moderate and high speed the maximal (2% and 5%, respectively)
      and average (both 5%) vertical force and associated impulse (10% and 14%) were
      greater with SWING (all P<0.05). At high speed range of motion and angular
      velocity of knee flexion were 24% greater with SWING (both P<0.05), while average
      EMG of m. biceps femoris was 31% lower (all P<0.05) in SWING. In a similar
      manner, the average EMG of m. vastus medialis and m. biceps femoris were lower
      (17% and 32%, P<0.05) during the following knee extension. Thus, swinging the
      arms while performing V2-alternate can enhance both maximal speed and skiing
      economy at moderate and, in particularly, high speeds. 

PMID- 27031074
TI  - The role of angiogenesis in implant dentistry part II: The effect of bone
      grafting and barrier membrane materials on angiogenesis.
AB  - BACKGROUND: In implant dentistry, bone substitute materials and barrier membranes
      are used in different treatments including guided bone regeneration (GBR), socket
      preservation, alveolar ridge augmentation, maxillary sinus elevation, and filling
      bony defects around the inserted dental implant. One of the most important
      factors in prognosis of treatments using these materials is the growth of new
      blood vessels in applied areas. Present review was performed to evaluate the
      effect of the bone-grafting and barrier membrane materials on angiogenesis
      events. MATERIAL AND METHODS: An electronic search was performed in PubMed,
      MEDLINE, and EMBASE databases via OVID using the keywords mentioned in the PubMed
      and MeSH headings regarding the role of angiogenesis in implant dentistry from
      January 2000-April 2014. RESULTS: Of the 5,622 articles identified in our initial
      search results, only 33 met the inclusion criteria set for this review. Among
      bone substitute materials the autogenous bone-grafts, and among the barrier
      membranes the collagenous membranes, had the highest angiogenic potentials. Other
      bone-grafting materials or membranes were mostly used with pro-angiogenic factors
      to enhance their angiogenic properties. CONCLUSIONS: Angiogenesis is one of the
      key factors, which plays a critical role in success rate of GBR technique and is
      seriously considered in manufacturing bone-grafting and barrier membrane
      materials. However, there is still lack of clinical and in-vivo studies
      addressing the effect of angiogenesis in treatments using bone-grafting and
      barrier membrane materials.

PMID- 27031076
TI  - Rewiring Multidomain Protein Switches: Transforming a Fluorescent Zn(2+) Sensor
      into a Light-Responsive Zn(2+) Binding Protein.
AB  - Protein-based sensors and switches provide attractive tools for the real-time
      monitoring and control of molecular processes in complex biological environments.
      Fluorescent sensor proteins have been developed for a wide variety of small
      molecules, but the construction of genetically encoded light-responsive ligand
      binding proteins remains mostly unexplored. Here we present a generic approach to
      reengineer a previously developed FRET-based Zn(2+) sensor into a light
      activatable Zn(2+) binding protein using a design strategy based on mutually
      exclusive domain interactions. These so-called VividZn proteins consist of two
      light-responsive Vivid domains that homodimerize upon illumination with blue
      light, thus preventing the binding of Zn(2+) between two Zn(2+) binding domains,
      Atox1 and WD4. Following optimization of the linker between WD4 and the N
      terminus of one of the Vivid domains, VividZn variants were obtained that show a
      9- to 55-fold decrease in Zn(2+) affinity upon illumination, which is fully
      reversible following dark adaptation. The Zn(2+) affinities of the switch could
      be rationally tuned between 1 pM and 2 nM by systematic variation of linker
      length and mutation of one of the Zn(2+) binding residues. Similarly,
      introduction of mutations in the Vivid domains allowed tuning of the switching
      kinetics between 10 min and 7 h. Low expression levels in mammalian cells
      precluded the demonstration of light-induced perturbation of cytosolic Zn(2+)
      levels. Nonetheless, our results firmly establish the use of intramolecular Vivid
      dimerization as an attractive light-sensitive input module to rationally engineer
      light-responsive protein switches based on mutually exclusive domain
      interactions.

PMID- 27031077
TI  - Articulating spacers compared to fixed spacers for the treatment of infected knee
      arthroplasty: A follow-up of 37 cases.
AB  - BACKGROUND: The standard treatment of a periprosthetic infection after TKA
      involves a two-stage reimplantation with the intermittent implantation of
      spacers. Different designs of spacers have been described; currently articulating
      spacers and fixed spacers are used. The aim of the present study is to compare
      the advantages/disadvantages of the different spacers. PATIENTS AND METHODS: In
      this retrospective study we analyzed 37 cases after revision surgery of infected
      TKA. All patients that received spacers as part of the two-stage reimplantation
      were included. Exclusion criteria were massive bone loss prior to revision,
      because the implantation of a mobile spacer would not have been possible.
      RESULTS: The average ROM was 98.0 (+/- 14.9) degrees in the articulating spacer
      group (group 1) and 79.3 (+/- 22.5) in the group that received the fixed spacers
      (group 2) before revision surgery started. At a late follow up the average ROM
      for group 1 was 102.0 (+/- 8.4) and 79.0 (+/- 26) for group 2. CONCLUSION: The
      use of articulating spacers in the two-stage revision for infected total knee
      arthroplasty is a safe alternative to fixed spacers, that equally preserves
      ligament balancing and has equal infection eradication rates. A long term
      improvement of the range of motion following reimplantation of the new joint was,
      however, not observed.

PMID- 27031078
TI  - Clinical efficacy and safety of a new flexible interbody spacer system.
AB  - BACKGROUND: Patients with lumbar degenerative disk disease (DDD) often require an
      interbody fusion. Several spacer systems have been developed to achieve an
      adequate fusion. The newly developed flexible interbody spacer system (Luna(r),
      Benvenue Medical Inc.) expands to the disk space and is adjustable to the
      patient's anatomy. OBJECTIVE: Prospective monocentric evaluation of interbody
      fusions performed with the new system in patients with DDD to assess the device's
      efficacy and safety. METHODS: The study includes patients with DDD of one or two
      contiguous lumbar levels. All patients were treated with the new flexible cage
      system. To evaluate the clinical outcome, examinations were conducted
      preoperatively, 6 weeks, 6 months and 12 months postoperatively. At each study
      visit possible implant loosening was assessed by plain radiography and any
      adverse events were documented. Furthermore, back pain was evaluated using the
      visual analogue scale (VAS), functional impairment using the Oswestry-Disability
      Index (ODI) and quality of life using the SF36. RESULTS: A total of 30 patients
      (age: 52.8 +/- 11 years, gender: 53% male) were included. None of the patients
      showed signs of implant loosening and the total number of adverse events was low
      (3%). The VAS improved significantly from 81.2 +/- 9.5 mm at baseline to 28 +/-
      26.2 mm after 12-months (p <= 0.0001). The ODI also improved significantly from
      57.9 +/- 9.6% at baseline to 20 +/- 15.6% after 12-months (p <= 0.0001). The
      physical component score (PCS) of the SF36 improved significantly ongoing from
      29.2 +/- 9.3 at baseline to 56.1 +/- 14.9 after 12-months (p = 0.0079) and the
      mental component score (MCS) improved significantly from 49.2 +/- 20.7 at
      baseline to 62.8 +/- 18.9 after 12 months (p = 0.013). CONCLUSIONS: Minimal
      invasive lumbar interbody fusion with the new flexible system is a safe and
      effective treatment method for patients with DDD. Complication rates are low and
      treatment leads to an improvement of pain, functional impairment and quality of
      life.

PMID- 27031079
TI  - Women with PTSD benefit more from psychotherapy than men.
AB  - OBJECTIVE: This study aimed to examine possible gender differences in therapy
      gain in patients with posttraumatic stress disorder (PTSD). It also aimed to
      examine whether the gender effect could be explained by gender differences in
      dropout rates, trauma type (interpersonal/noninterpersonal), or context of the
      event (work-related/not work-related). METHOD: Seventy-one participants received
      20-session cognitive-behavior therapy for PTSD. They were assessed pre- and
      posttreatment on primary and secondary outcome measures: PTSD symptoms, quality
      of life, avoidance, social support and positive reappraisal copings, and
      supportive and countersupportive interactions. RESULTS: Regression analysis
      showed that gender explained 6%-9% significant variance in the outcome: Women
      statistically benefited more from the treatment than men on quality of life (p <
      .05), avoidance (p < .01), and support seeking (p < .05) copings, supportive (p <
      .05), and countersupportive (p < .05) interactions. However, there was no
      statistically significant gender difference on PTSD symptoms and positive
      reappraisal coping. Dropout rate, trauma type, and context of trauma could not
      explain the gender differences. CONCLUSION: The results might explain ambiguous
      previous results on gender differences in therapy efficacy for PTSD, and
      highlight the importance of using multiple measurements in the evaluation of
      treatment outcome in PTSD. Further research is needed to explain the exact
      mechanisms behind women's getting more of therapy's secondary benefits. (PsycINFO
      Database Record

PMID- 27031080
TI  - Childhood trauma and posttraumatic stress disorder in a real-world Veterans
      Affairs clinic: Examining treatment preferences and dropout.
AB  - OBJECTIVE: The Department of Veterans Affairs (VA) has promoted large-scale
      dissemination efforts of evidence-based psychotherapies (EBPs) for posttraumatic
      stress disorder (PTSD). In spite of efforts to make gold-standard treatments
      available to veterans, few veterans with PTSD receive a full course of
      psychotherapy. It is unclear if type of trauma experienced is related to
      treatment initiation and completion. This study aimed to identify patient
      factors, including experiencing childhood trauma that related to treatment
      preferences and dropout in a real-world VA PTSD clinic. METHOD: A chart review
      was conducted for veterans who were referred for individual EBPs for PTSD (N =
      199). Extracted variables included demographics, PTSD symptoms, treatment
      preferences, and treatment completion/dropout. RESULTS: Veterans choose to engage
      in individual EBP (48%), group treatment (11%), nontrauma focused psychotherapy
      (15%), or no psychotherapy (26%). Slightly over half of the veterans who began
      individual EBP completed it, with no statistical differences in completion rates
      for prolonged exposure and cognitive processing therapy. Childhood trauma was the
      second-most common type of trauma experienced, next to combat exposure. Those who
      completed EBP had higher rates of combat trauma (88%) than noncompleters (70%),
      and noncompleters (50%) had higher rates of childhood trauma than completers
      (29%). Regardless of trauma experienced, those who completed an EBP experienced
      substantial reductions in PTSD symptoms. CONCLUSIONS: Assessing veterans for
      childhood trauma and emotion regulation difficulties may be beneficial even in VA
      clinics where treatment is most often focused on combat trauma. (PsycINFO
      Database Record

PMID- 27031081
TI  - Pathological spirit possession as a cultural interpretation of trauma-related
      symptoms.
AB  - OBJECTIVE: Spirit possession is a phenomenon frequently occurring in war-torn
      countries. It has been shown to be an idiom of distress entailing dissociative
      symptoms. However, its association with trauma exposure and trauma-related
      disorders remains unclear. This study aimed to explore subjective disease models
      and the relationship between pathological spirit possession and trauma-related
      disorders in the Eastern Democratic Republic of the Congo. METHOD: Seventy-three
      (formerly) possessed persons (74% female, mean age = 34 years), referred by
      traditional and spiritual healers, were interviewed about their experiences of
      pathological spirit possession, trauma exposure, posttraumatic stress disorder
      (PTSD) symptoms, depressive symptoms, shame and guilt, psychotic symptoms,
      somatic complaints, and the impairment of psychosocial functioning. RESULTS: The
      most common disease model for pathological spirit possession was another person
      having sent the spirit, mostly a family member or a neighbor, out of jealousy or
      conflict over resources. Significant correlations were found between spirit
      possession over lifetime and PTSD symptom severity, feelings of shame and guilt,
      depressive symptoms, somatic complaints, and psychotic symptoms. Spirit
      possession during the preceding 4 weeks was associated with PTSD symptom
      severity, impairment of psychosocial functioning, and psychotic symptom severity.
      CONCLUSIONS: The results of this study indicate that pathological spirit
      possession is a broad explanatory framework for various subjectively
      unexplainable mental and physical health problems, including but not limited to
      trauma-related disorders. Understanding pathological spirit possession as a
      subjective disease model for various mental and physical health problems may help
      researchers and clinicians to develop culturally sensitive treatment approaches
      for affected individuals. (PsycINFO Database Record

PMID- 27031082
TI  - Announcement: Sudden Death in the Young Case Registry.
AB  - Approximately 3,500 infants die suddenly and unexpectedly each year in the United
      States. Less is known about the incidence in children because epidemiologic
      studies of these deaths in children are rare. The increased mortality risk in
      children with undetected heart conditions or epilepsy highlights the need for
      expanded surveillance to identify sudden unexpected death associated with these
      conditions.

PMID- 27031083
TI  - Phenotype-driven gene target definition in clinical genome-wide sequencing data
      interpretation.
AB  - PURPOSE: Genome-wide sequencing approaches are increasingly being used in place
      of disease gene panel sequencing approaches. Despite the well-recognized benefits
      of these approaches, they also carry with them an increased burden of analyzing
      overwhelmingly large gene targets and an increased possibility of detecting
      incidental findings. METHODS: We propose a novel approach for design of
      individualized phenotype gene panels using the set of signs and symptoms observed
      and selecting relevant genes on the basis of known phenotype-gene associations.
      RESULTS: We used results of diagnostic exome sequencing in 405 cases submitted to
      our institution to show retrospectively that using the phenotype gene panel
      increases the sensitivity of masked exome analysis (increase from 25.4 to 29.7%
      in overall diagnostic yield). We also show that such a strategy enables the
      possibility of masked analysis of genome-wide sequencing data in patients with
      poorly defined and multifaceted clinical presentations. Ultimately, we show that
      this approach enables control over the incidental findings rate (0.25% in
      phenotype gene panels). Finally, we provide a Web tool for customized phenotype
      panel creation (available at http://www.kimg.eu/generator). CONCLUSION: In
      conclusion, we present a novel approach to a phenotype-driven diagnostic process
      of genome scale sequencing data that harnesses the sensitivity of these
      approaches while restricting the analysis to genes relevant to clinical
      presentation in patient.Genet Med 18 11, 1102-1110.

PMID- 27031084
TI  - Low risk of solid tumors in persons with Down syndrome.
AB  - PURPOSE: The aim of this study was to investigate cancer incidence in a large
      cohort of persons with Down syndrome. METHODS: Down syndrome was identified from
      the Danish Cytogenetic Register. Cancer occurrence was identified by linkage to
      the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95%
      confidence intervals (CIs) were calculated based on observed and expected numbers
      from rates for all Danish residents. The cohort consisted of 3,530 persons with
      Down syndrome contributing 89,570 person-years at risk. RESULTS: Acute leukemia
      risk was highest from 1-4 years of age and remained elevated until age 30. The
      overall risk of solid tumors was decreased (SIR 0.45; 95% CI 0.34-0.59),
      especially in persons 50 years or older (SIR 0.27; 95% CI 0.16-0.43). We found a
      significantly lower risk of lung cancer (SIR 0.10; 95% CI 0.00-0.56), breast
      cancer (SIR 0.16; 95% CI 0.03-0.47), and cervical cancer (SIR 0.0; 95% CI 0.00
      0.77). Testicular cancer was the only solid tumor with an increased SIR (2.9; 95%
      CI 1.6-4.8). CONCLUSIONS: The risk of all major groups of solid tumors was
      decreased, except testicular cancer. Altered screening strategies should be
      considered for persons with Down syndrome. This unusual pattern of cancer
      occurrence may help understanding carcinogenesis in the general population.Genet
      Med 18 11, 1151-1157.

PMID- 27031085
TI  - Biobanks and consent with a terminal clause.

PMID- 27031087
TI  - Anticipated effects of alcohol stimulate craving and impair inhibitory control.
AB  - A considerable evidence base has demonstrated that priming doses of alcohol
      impair inhibitory control and activate motivation to consume alcohol. There is,
      however, a lack of studies investigating the effect of placebo-alcohol on these
      processes and their association with alcohol outcome expectancies (AOE). We
      investigated the effect of placebo-alcohol on craving and inhibitory control, and
      the extent to which placebo effects correlated with AOE in 32 nondependent
      drinkers. Participants completed questionnaires assessing typical alcohol use
      (fortnightly alcohol consumption, AUDIT) and AOE (measured using the Alcohol
      Outcome Expectancy Scale). On a within-subjects basis participants consumed a
      placebo-alcohol drink and control drink. Measures of craving were taken pre- and
      postdrink, and participants completed a go/no-go task following the drink.
      Craving was increased by the placebo-alcohol and, importantly, placebo-alcohol
      impaired inhibitory control. Furthermore expectancies of cognitive and behavioral
      impairment were correlated with go/no-go task performance following a placebo.
      Increases in craving were associated with a range of elevated outcome
      expectancies. This suggests that the anticipated effects of alcohol can impair
      inhibitory control and increase craving; therefore studies using placebo versus
      alcohol comparisons relative to studies using a pure no-alcohol control are
      underestimating the real-world effect of alcohol on these processes, which is a
      combination of pharmacological and anticipated effects of alcohol. Furthermore,
      individual differences in AOE may influence reactivity to the anticipated effects
      of alcohol. (PsycINFO Database Record

PMID- 27031086
TI  - Developmental trends in alcohol use initiation and escalation from early to
      middle adolescence: Prediction by urgency and trait affect.
AB  - Studies on adolescent drinking have not always been able to distinguish between
      initiation and escalation of drinking, because many studies include samples in
      which initiation has already occurred; hence, initiation and escalation are often
      confounded. The present study draws from a dual-process theoretical framework to
      investigate: if changes in the likelihood of drinking initiation and escalation
      are predicted by a tendency toward rash action when experiencing positive and
      negative emotions (positive and negative urgency) and whether trait positive and
      negative affect moderate such effects. Alcohol naive adolescents (n = 944; age M
      = 12.16, SD = .96; 52% female) completed 6 semiannual assessments of trait
      urgency and affect (Wave 1) and alcohol use (Waves 2-6). A 2-part random-effects
      model was used to estimate changes in the likelihood of any alcohol use versus
      escalation in the volume of use among initiators. Main effects suggest a
      significant association between positive affect and change in level of alcohol
      use among initiators, such that lower positive affect predicted increased alcohol
      involvement. This main effect was qualified by a significant interaction between
      positive urgency and positive affect predicting changes in the escalation of
      drinking, such that the effect of positive urgency was augmented for those high
      on trait positive affect, though only at extremely high levels of positive
      affect. Results suggest risk factors in the development of drinking depend on
      whether initiation or escalation is investigated. A more nuanced understanding of
      the early developmental phases of alcohol involvement can inform prevention and
      intervention efforts. (PsycINFO Database Record

PMID- 27031088
TI  - The resilience scale for adults in italy: A validation study comparing clinical
      substance abusers with a nonclinical sample.
AB  - This article reports a validation study of the Italian version of the Resilience
      Scale for Adults (RSA), a measure designed to assess individual, family, and
      social resilience protective resources. The RSA was administered to a clinical
      (i.e., substance use disorders, or SUD; N = 437) and a nonclinical sample (N =
      337). A confirmatory factor analyses supported the original 6-factor structure of
      the RSA in both samples. The RSA correlated positively with functional coping
      strategies and negatively with perceived stress and dysfunctional coping
      strategies. Moreover, the RSA subscales discriminated between SUD and non-SUD
      individuals. Factorial invariance testing also confirmed comparable psychometric
      properties across gender. The results confirm good psychometric properties of the
      Italian RSA and provide support for the construct validity of the scale. The RSA
      may be suited for use in studies examining natural course and intervention
      trials. (PsycINFO Database Record

PMID- 27031089
TI  - Time course of attentional bias to drug cues in opioid dependence.
AB  - Prior research indicates attentional bias to drug cues in opioid dependence. As
      this bias may be a marker of vulnerability to relapse following treatment, it is
      useful to clarify its underlying processes. The present study examined whether
      the opioid-related bias operates in early attention processes such as initial
      orienting, or in maintained attention, or both. Evidence from prior research is
      limited and mixed. The time course of attentional bias for drug cues was assessed
      using a dot-probe task with pictorial drug cues presented at 3 stimulus exposure
      durations: 200, 500 and 1,500 ms. There were 2 groups: opioid-dependent (n = 19)
      and healthy controls (n = 20). Individuals in the opioid-dependent group were
      recruited from community drug and alcohol treatment services; 95% were taking
      methadone. Compared with the control group, the opioid-dependent group showed a
      significant attentional bias for opioid-related information presented at 200 ms
      (p = .006). There was a similar trend at 500 ms which was nonsignificant (p =
      .057), and no bias at 1,500 ms (p = .698). The findings indicate an attentional
      bias to drug cues in opioid dependence, which operates in initial orienting
      processes, but not maintained attention. Further research should examine whether
      modification of this bias by treatment reduces risk of relapse. (PsycINFO
      Database Record

PMID- 27031090
TI  - Human immune cell targeting of protein nanoparticles--caveospheres.
AB  - Nanotechnology has the power to transform vaccine and drug delivery through
      protection of payloads from both metabolism and off-target effects, while
      facilitating specific delivery of cargo to immune cells. However, evaluation of
      immune cell nanoparticle targeting is conventionally restricted to monocultured
      cell line models. We generated human caveolin-1 nanoparticles, termed
      caveospheres, which were efficiently functionalized with monoclonal antibodies.
      Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting
      within physiological mixtures of primary human blood immune cells using flow
      cytometry, imaging flow cytometry and confocal microscopy. Antibody
      functionalization enhanced caveosphere binding to targeted immune cells (6.6 to
      43.9-fold) within mixed populations and in the presence of protein-containing
      fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere
      internalization by non-phagocytic CD4+ T cells--an important therapeutic target
      for HIV treatment. This efficient and flexible system of immune cell-targeted
      caveosphere nanoparticles holds promise for the development of advanced
      immunotherapeutics and vaccines.

PMID- 27031091
TI  - Conjunctival Lesions and Vision Impairment After Gastrointestinal Surgery.

PMID- 27031092
TI  - Duration of Adjuvant Therapy for Patients With Gastrointestinal Stromal Tumors:
      Where Is Goldilocks When We Need Her?

PMID- 27031093
TI  - Benzothiazole Sulfinate: a Water-Soluble and Slow-Releasing Sulfur Dioxide Donor.
AB  - Sulfur dioxide (SO2) has long been considered a toxic environmental pollutant and
      byproduct of industrial processing. Recently it has become evident that SO2 may
      also have regulatory functions in mammalian pulmonary systems. However, the study
      of these effects has proven to be challenging due to the difficulty in
      administering SO2 in a reliable manner. In this work, we report the discovery of
      a new pH-dependent and water-soluble SO2 donor, benzothiazole sulfinate (BTS). We
      have found BTS to have slow and sustained SO2 release at physiological pH.
      Additionally, we have explored its vasorelaxation properties as compared to the
      authentic SO2 gas solutions. The slow release of BTS should make it a useful tool
      for the study of endogenously generated SO2.

PMID- 27031094
TI  - Evaluations of Mesogen Orientation in Thin Films of Polyacrylate with
      Cyanobiphenyl Side Chain.
AB  - The orientation behavior of mesogens in a polyacrylate with cyanobiphenyl (CB)
      side chain in thin films was investigated in detail by UV-vis absorption
      spectroscopy and grazing incidence small-angle X-ray scattering (GI-SAXS)
      measurements using both high-energy X-rays of Cu Kalpha line (lambda = 0.154 nm)
      and low-energy synchrotron X-rays (lambda = 0.539 nm). By changing the film
      thickness ranging 7-200 nm, it is concluded that the planar orientation is
      predominant for thin films with thickness below 10-15 nm. This planar mesogen
      orientation near the substrate surface coexists with the homeotropically aligned
      CB mesogens in films thicker than 30 nm. For the thinnest 7 nm film, the planar
      orientation is unexpectedly lost, which is in consort with a disordering of
      smectic layer structure. Peculiar orienting characteristics of CB mesogen are
      suggested, which probably stem from the tendency to form an antiparallel
      arrangement of mesogens due to the strong dipole moment of the terminal cyano
      group. 

PMID- 27031096
TI  - Numerical Simulation of CO2 Flooding of Coalbed Methane Considering the Fluid
      Solid Coupling Effect.
AB  - CO2 flooding of coalbed methane (CO2-ECBM) not only stores CO2 underground and
      reduces greenhouse gas emissions but also enhances the gas production ratio. This
      coupled process involves multi-phase fluid flow and coal-rock deformation, as
      well as processes such as competitive gas adsorption and diffusion from the coal
      matrix into fractures. A dual-porosity medium that consists of a matrix and
      fractures was built to simulate the flooding process, and a mathematical model
      was used to consider the competitive adsorption, diffusion and seepage processes
      and the interaction between flow and deformation. Due to the effects of the
      initial pressure and the differences in pressure variation during the production
      process, permeability changes caused by matrix shrinkage were spatially variable
      in the reservoir. The maximum value of permeability appeared near the production
      well, and the degree of rebound decreased with increasing distance from the
      production well. 

PMID- 27031095
TI  - Epithelium Expressing the E7 Oncoprotein of HPV16 Attracts Immune-Modulatory
      Dendritic Cells to the Skin and Suppresses Their Antigen-Processing Capacity.
AB  - Antigen presenting cells (APCs) in skin can promote either antigen-specific
      effector functions or antigen tolerance, and thus determine clearance or
      persistence of cutaneous viral infections. Human papillomavirus (HPV) infections
      can persist in squamous epithelium in immunocompetent individuals, and some
      persisting HPV infections, particularly with HPV16, promote malignant epithelial
      transformation. Here, we investigate whether local expression of the HPV16
      protein most associated with malignant transformation, HPV16-E7, affects the
      phenotype and function of APC subsets in the skin. We demonstrate an expanded
      population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell
      surface markers which express immune-modulatory enzymes and cytokines not
      expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene
      expression in keratinocytes attracts new APC subsets to the epidermis. In vivo
      migration and transport of antigen to the draining lymph node by these APCs is
      markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as
      measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by
      APCs, is significantly impaired. These data suggest that local expression of
      HPV16-E7 in keratinocytes can contribute to persisting infection with this
      oncogenic virus, by altering the phenotype and function of local APCs. 

PMID- 27031097
TI  - Selective Synthesis and Derivatization of Germasilicon Hydrides.
AB  - Mixed Si/Ge hydrides SixGeyHz are valuable precursors for the deposition of
      binary Si-Ge alloys. This work describes the synthesis and full characterization
      of the previously unknown germaisotetrasilane Ph3GeSi(SiH3)3 (2) on a multigram
      scale from the reaction of the lithium silanide LiSi(SiH3)3 with Ph3GeCl. The
      stability of the Si-Ge bond in 2 versus electrophiles and nucleophiles has been
      investigated with the primary aim of developing new approaches to mixed sila-H
      germanes (H3Ge)xSi(SiH3)4-x. With 1 equiv of MeLi, 2 reacted cleanly under
      cleavage of one Si-Si bond to give Ph3GeSi(SiH3)2Li, which is a valuable synthon
      for further derivatization. In contrast, the dephenylation reaction of 2 with 1
      or 2 equiv of CF3SO3H/iBu2AlH proceeded much less selectively and afforded the
      desired Ph/H-germasilanes Ph2HGeSi(SiH3)3 and PhH2GeSi(SiH3)3 along with
      considerable amounts of Si-Ge scission products. 

PMID- 27031098
TI  - Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF
      Levels in Response to the T Cell Independent Immunogen Pneumovax(r)23.
AB  - Protective immunity against T cell independent (TI) antigens such as
      Streptococcus pneumoniae is characterized by antibody production of B cells
      induced by the combined activation of T cell independent type 1 and type 2
      antigens in the absence of direct T cell help. In mice, the main players in TI
      immune responses have been well defined as marginal zone (MZ) B cells and B-1
      cells. However, the existence of human equivalents to these B cell subsets and
      the nature of the human B cell compartment involved in the immune reaction remain
      elusive. We therefore analyzed the effect of a TI antigen on the B cell
      compartment through immunization of healthy individuals with the pneumococcal
      polysaccharide (PnPS)-based vaccine Pneumovax(r)23, and subsequent
      characterization of B cell subpopulations. Our data demonstrates a transient
      decrease of transitional and naive B cells, with a concomitant increase of IgA+
      but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific
      IgA+ producing plasma cells. No alterations could be detected in T cells, or
      proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI
      immune response, antigen-specific memory responses could not be observed.
      Finally, BAFF, which is supposed to drive class switching to IgA, was
      unexpectedly found to be decreased in serum in response to Pneumovax(r)23. Our
      results demonstrate that a characteristic TI response induced by Pneumovax(r)23
      is associated with distinct phenotypical and functional changes within the B cell
      compartment. Those modulations occur in the absence of any modulations of T cells
      and without the development of a specific memory response. 

PMID- 27031099
TI  - The Effectiveness of Individualized Acupuncture Protocols in the Treatment of
      Gulf War Illness: A Pragmatic Randomized Clinical Trial.
AB  - BACKGROUND: Gulf War Illness is a Complex Medical Illness characterized by
      multiple symptoms, including fatigue, sleep and mood disturbances, cognitive
      dysfunction, and musculoskeletal pain affecting veterans of the first Gulf War.
      No standard of care treatment exists. METHODS: This pragmatic Randomized Clinical
      Trial tested the effects of individualized acupuncture treatments offered in
      extant acupuncture practices in the community; practitioners had at least 5 years
      of experience plus additional training provided by the study. Veterans with
      diagnosed symptoms of Gulf War Illness were randomized to either six months of
      biweekly acupuncture treatments (group 1, n = 52) or 2 months of waitlist
      followed by weekly acupuncture treatments (group 2, n = 52). Measurements were
      taken at baseline, 2, 4 and 6 months. The primary outcome is the SF-36 physical
      component scale score (SF-36P) and the secondary outcome is the McGill Pain
      scale. RESULTS: Of the 104 subjects who underwent randomization, 85 completed the
      protocol (82%). A clinically and statistically significant average improvement of
      9.4 points (p = 0.03) in the SF-36P was observed for group 1 at month 6 compared
      to group 2, adjusting for baseline pain. The secondary outcome of McGill pain
      index produced similar results; at 6 months, group 1 was estimated to experience
      a reduction of approximately 3.6 points (p = 0.04) compared to group 2.
      CONCLUSIONS: Individualized acupuncture treatment of sufficient dose appears to
      offer significant relief of physical disability and pain for veterans with Gulf
      War Illness. This work was supported by the Office of the Assistant Secretary of
      Defense for Health Affairs through the Gulf War Illness Research Program under
      Award No. W81XWH-09-2-0064. Opinions, interpretations, conclusions and
      recommendations are those of the author and are not necessarily endorsed by the
      Department of Defense. TRIAL REGISTRATION: ClinicalTrials.gov NCT01305811.

PMID- 27031100
TI  - Molecular Taxonomic Evidence for Two Distinct Genotypes of Mycobacterium
      yongonense via Genome-Based Phylogenetic Analysis.
AB  - Recently, we introduced a distinct Mycobacterium intracellulare INT-5 genotype,
      distantly related to other genotypes of M. intracellulare (INT-1 to -4). The aim
      of this study is to determine the exact taxonomic status of the M. intracellulare
      INT-5 genotype via genome-based phylogenetic analysis. To this end, genome
      sequences of the two INT-5 strains, MOTT-H4Y and MOTT-36Y were compared with M.
      intracellulare ATCC 13950(T) and Mycobacterium yongonense DSM 45126(T). Our
      phylogenetic analysis based on complete genome sequences, multi-locus sequence
      typing (MLST) of 35 target genes, and single nucleotide polymorphism (SNP)
      analysis indicated that the two INT-5 strains were more closely related to M.
      yongonense DSM 45126(T) than the M. intracellulare strains. These results suggest
      their taxonomic transfer from M. intracellulare into M. yongonense. Finally, we
      selected 5 target genes (argH, dnaA, deaD, hsp65, and recF) and used SNPs for the
      identification of M. yongonese strains from other M. avium complex (MAC) strains.
      The application of the SNP analysis to 14 MAC clinical isolates enabled the
      selective identification of 4 M. yongonense clinical isolates from the other
      MACs. In conclusion, our genome-based phylogenetic analysis showed that the
      taxonomic status of two INT-5 strains, MOTT-H4Y and MOTT-36Y should be revised
      into M. yongonense. Our results also suggest that M. yongonense could be divided
      into 2 distinct genotypes (the Type I genotype with the M. parascrofulaceum rpoB
      gene and the Type II genotype with the M. intracellulare rpoB gene) depending on
      the presence of the lateral gene transfer of rpoB from M. parascrofulaceum.

PMID- 27031101
TI  - Improving Osteoblast Response In Vitro by a Nanostructured Thin Film with
      Titanium Carbide and Titanium Oxides Clustered around Graphitic Carbon.
AB  - INTRODUCTION: Recently, we introduced a new deposition method, based on Ion
      Plating Plasma Assisted technology, to coat titanium implants with a thin but
      hard nanostructured layer composed of titanium carbide and titanium oxides,
      clustered around graphitic carbon. The nanostructured layer has a double effect:
      protects the bulk titanium against the harsh conditions of biological tissues and
      in the same time has a stimulating action on osteoblasts. RESULTS: The aim of
      this work is to describe the biological effects of this layer on osteoblasts
      cultured in vitro. We demonstrate that the nanostructured layer causes an
      overexpression of many early genes correlated to proteins involved in bone
      turnover and an increase in the number of surface receptors for alpha3beta1
      integrin, talin, paxillin. Analyses at single-cell level, by scanning electron
      microscopy, atomic force microscopy, and single cell force spectroscopy, show how
      the proliferation, adhesion and spreading of cells cultured on coated titanium
      samples are higher than on uncoated titanium ones. Finally, the chemistry of the
      layer induces a better formation of blood clots and a higher number of adhered
      platelets, compared to the uncoated cases, and these are useful features to
      improve the speed of implant osseointegration. CONCLUSION: In summary, the
      nanostructured TiC film, due to its physical and chemical properties, can be used
      to protect the implants and to improve their acceptance by the bone.

PMID- 27031103
TI  - Social Justice and Social Order: Binding Moralities across the Political
      Spectrum.
AB  - Two studies explored the relationship between political ideology and endorsement
      of a range of moral principles. Political liberals and conservatives did not
      differ on intrapersonal or interpersonal moralities, which require self
      regulation. However differences emerged on collective moralities, which involve
      social regulation. Contrary to Moral Foundations Theory, both liberals and
      conservatives endorsed a group-focused binding morality, specifically Social
      Justice and Social Order respectively. Libertarians were the group without a
      binding morality. Although Social Justice and Social Order appear conflictual,
      analyses based on earlier cross-cultural work on societal tightness-looseness
      suggest that countries actually benefit in terms of economic success and societal
      well-being when these group-based moralities co-exist and serve as counterweights
      in social regulation. 

PMID- 27031102
TI  - Synergetic Effects of K, Ca, Cu and Zn in Human Semen in Relation to Parameters
      Indicative of Spontaneous Hyperactivation of Spermatozoa.
AB  - We have observed that sperm quality parameters indicative of spermatozoa
      hyperactivation such are lower "linearity" and "straightness", and as showed by
      this research "elongation", were more pronounced in patients with normal
      spermiogram compared to the group of men with reduced sperm motility who were
      undergoing routine in vitro fertilisation. The research encompassed 97 men
      diagnosed with normozoospermia (n = 20), asthenozoospermia (n = 54) and
      oligoasthenozoospermia (n = 23). The findings indicate that sperm quality of
      patients with normal spermiogram diagnosed according to WHO criteria, may be
      compromised by showing premature spontaneous hyperactivation which can decrease
      the chances of natural conception. We assessed synergistic effects of multiple
      chemical elements in ejaculated semen to find if premature spontaneous
      hyperactivation of spermatozoa can be a sign of imbalanced semen composition
      especially of elements K, Ca, Cu and Zn. Human semen samples showing low or high
      baseline status of chemical elements concentrations were found in samples from
      all three diagnostic groups. However, correlation of K/Ca and Cu/Zn ratios,
      taking into account samples from all three groups of men, were negative at
      statistical significance level p = 0.01. We tested if the negative correlation
      between K/Ca and Cu/Zn ratio works for greater number of semen samples. We found
      the negative correlation to be valid for 175 semen samples at statistical
      significance of p = 0.00002. The ratio of K/Ca and Cu/Zn, i.e. increased
      concentrations of K and Zn in comparison to concentrations of Ca and Cu, were
      associated with a decrease of "straightness" in the group of men with normal
      spermiogram and pronounced spontaneous hyperactivation of spermatozoa, implying
      that these elements act in synergy and that the balance of elements and not their
      absolute concentrations plays the major role in premature spermatozoa
      hyperactivation in ejaculated semen. 

PMID- 27031104
TI  - Submergence Tolerance and Germination Dynamics of Roegneria nutans Seeds in Water
      Level Fluctuation Zones with Different Water Rhythms in the Three Gorges
      Reservoir.
AB  - The Three Gorges Dam features two water-level fluctuation zones (WLFZs): the
      preupland drawdown zone (PU-DZ) and the preriparian drawdown zone (PR-DZ). To
      investigate the vegetation potential of Roegneria nutans in WLFZs, we compared
      the submergence tolerance and germination dynamics in the natural riparian zone
      (NRZ), PU-DZ and PR-DZ. We found that the NRZ seeds maintained an 81.3%
      intactness rate and >91% germination rate. The final seed germination rate and
      germination dynamics were consistent with those of the controls. Meanwhile, the
      PU-DZ seeds submerged at 5 m, 10 m, 15 m, and 20 m exhibited intactness rates of
      70.5%, 79.95%, 40.75%, and 39.87%, respectively, and >75% germination.
      Furthermore, the PR-DZ seeds exhibited intactness rates of 22.44%, 61.13%,
      81.87%, and 15.36% at 5 m, 10 m, 15 m, and 17 m, respectively, and 80%
      germination. The germination rates of the intact seeds submerged >10 m were >80%.
      Finally, the intact seeds germinated quickly in all WLFZs. The high proportion of
      intact seeds, rapid germination capacity, and high germination rate permit R.
      nutans seeds to adapt to the complicated water rhythms of the PU-DZ and PR-DZ and
      indicate the potential for their use in vegetation restoration and recovery.
      Thus, perennial seeds can be used for vegetation restoration in the WLFZs of
      large reservoirs and in other regions with water rhythms similar to the Three
      Gorges Reservoir. 

PMID- 27031106
TI  - S-100 B Concentrations Are a Predictor of Decreased Survival in Patients with
      Major Trauma, Independently of Head Injury.
AB  - BACKGROUND: Major trauma remains one of the principle causes of disability and
      death throughout the world. There is currently no satisfactory risk assessment to
      predict mortality in patients with major trauma. The aim of our study is to
      examine whether S-100 B protein concentrations correlate with injury severity and
      survival in patients with major trauma, with special emphasis on patients without
      head injury. METHODS: Our retrospective data analysis comprised adult patients
      admitted to our emergency department between 1.12. 2008 and 31.12 2010 with a
      suspected major trauma. S-100 B concentrations were routinely assessed in major
      trauma patients. RESULTS: A total of 27.7% (378) of all patients had major
      trauma. The median ISS was 24.6 (SD 8.4); 16.6% (63/378) of the patients died. S
      100 B concentrations correlated overall with the ISS (p<0.0001). Patients who
      died had significantly higher S-100 B concentrations than survivors (8.2 MUg/l
      versus 2.2 MUg/l, p<0.0001). Polytraumatised patients with and without head
      trauma did not differ significantly with respect to S-100 B concentration (3.2
      MUg/l (SD 5.3) versus 2.9 MUg/l (SD 3.8), respectively, p = 0.63) or with respect
      to Injury Severity Score (24.8 (SD 8.6) versus 24.2 (SD 8.1), respectively, p =
      0.56). S-100 B concentrations correlated negatively with survival (p<0.0001) in
      all patients and in both subgroups (p = 0.001 and p = 0.006, respectively).
      CONCLUSIONS: S-100 concentrations on admission correlate positively with greater
      injury severity and decreased survival in major trauma patients, independently of
      the presence of a head injury. S-100 B protein levels at admission in patients
      with major trauma may therefore be used to assess outcome in all polytraumatised
      patients. These measurements should be subject to further evaluation.

PMID- 27031107
TI  - Four Decades of Educational Inequalities in Hospitalization and Mortality among
      Older Swedes.
AB  - BACKGROUND: The inverse association between education and mortality has grown
      stronger the last decades in many countries. During the same period, gains in
      life expectancy have been concentrated to older ages; still, old-age mortality is
      seldom the focus of attention when analyzing trends in the education-mortality
      gradient. It is further unknown if increased educational inequalities in
      mortality are preceded by increased inequalities in morbidity of which
      hospitalization may be a proxy. METHODS: Using administrative population
      registers from 1971 and onwards, education-specific annual changes in the risk of
      death and hospital admission were estimated with complimentary log-log models.
      These risk changes were supplemented by estimations of the ages at which 25, 50,
      and 75% of the population had been hospitalized or died (after age 60). RESULTS:
      The mortality decline among older people increasingly benefitted the well
      educated over the less well-educated. This inequality increase was larger for the
      younger old, and among men. Educational inequalities in the age of a first
      hospital admission generally followed the development of growing gaps, but at a
      slower pace than mortality and inequalities did not increase among the oldest
      individuals. CONCLUSIONS: Education continues to be a significant predictor of
      health and longevity into old age. That the increase in educational inequalities
      is greater for mortality than for hospital admissions (our proxy of overall
      morbidity) may reflect that well-educated individuals gradually have obtained
      more possibilities or resources to survive a disease than less well-educated
      individuals have the last four decades.

PMID- 27031105
TI  - Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What
      Are the Lessons for Influenza Vaccination?
AB  - INTRODUCTION: Determining the optimal time to vaccinate is important for
      influenza vaccination programmes. Here, we assessed the temporal characteristics
      of influenza epidemics in the Northern and Southern hemispheres and in the
      tropics, and discuss their implications for vaccination programmes. METHODS: This
      was a retrospective analysis of surveillance data between 2000 and 2014 from the
      Global Influenza B Study database. The seasonal peak of influenza was defined as
      the week with the most reported cases (overall, A, and B) in the season. The
      duration of seasonal activity was assessed using the maximum proportion of
      influenza cases during three consecutive months and the minimum number of months
      with >=80% of cases in the season. We also assessed whether co-circulation of A
      and B virus types affected the duration of influenza epidemics. RESULTS: 212
      influenza seasons and 571,907 cases were included from 30 countries. In tropical
      countries, the seasonal influenza activity lasted longer and the peaks of
      influenza A and B coincided less frequently than in temperate countries. Temporal
      characteristics of influenza epidemics were heterogeneous in the tropics, with
      distinct seasonal epidemics observed only in some countries. Seasons with co
      circulation of influenza A and B were longer than influenza A seasons, especially
      in the tropics. DISCUSSION: Our findings show that influenza seasonality is less
      well defined in the tropics than in temperate regions. This has important
      implications for vaccination programmes in these countries. High-quality
      influenza surveillance systems are needed in the tropics to enable decisions
      about when to vaccinate.

PMID- 27031108
TI  - Protection against SHIV Challenge by Subcutaneous Administration of the Plant
      Derived PGT121 Broadly Neutralizing Antibody in Macaques.
AB  - Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown
      promise for prevention and treatment of HIV infection. However, multiple IV
      administrations in geographic locations with poor accessibility to medical care
      have practical limitations. We have assessed the efficacy of plant-derived PGT121
      delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a
      rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited
      a longer serum half-life than IV administration and was more consistent than
      intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a
      minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six
      macaques when delivered immediately post-challenge. These results suggest the
      utility of plant-derived bnAbs delivered SC for HIV prevention. 

PMID- 27031110
TI  - Understanding Financial Market States Using an Artificial Double Auction Market.
AB  - The ultimate value of theories describing the fundamental mechanisms behind asset
      prices in financial systems is reflected in the capacity of such theories to
      understand these systems. Although the models that explain the various states of
      financial markets offer substantial evidence from the fields of finance,
      mathematics, and even physics, previous theories that attempt to address the
      complexities of financial markets in full have been inadequate. We propose an
      artificial double auction market as an agent-based model to study the origin of
      complex states in financial markets by characterizing important parameters with
      an investment strategy that can cover the dynamics of the financial market. The
      investment strategies of chartist traders in response to new market information
      should reduce market stability based on the price fluctuations of risky assets.
      However, fundamentalist traders strategically submit orders based on fundamental
      value and, thereby stabilize the market. We construct a continuous double auction
      market and find that the market is controlled by the proportion of chartists, Pc.
      We show that mimicking the real state of financial markets, which emerges in real
      financial systems, is given within the range Pc = 0.40 to Pc = 0.85; however, we
      show that mimicking the efficient market hypothesis state can be generated with
      values less than Pc = 0.40. In particular, we observe that mimicking a market
      collapse state is created with values greater than Pc = 0.85, at which point a
      liquidity shortage occurs, and the phase transition behavior is described at Pc =
      0.85. 

PMID- 27031109
TI  - Structural and Genetic Studies Demonstrate Neurologic Dysfunction in
      Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle
      Dynamics.
AB  - Triosephosphate isomerase (TPI) deficiency is a poorly understood disease
      characterized by hemolytic anemia, cardiomyopathy, neurologic dysfunction, and
      early death. TPI deficiency is one of a group of diseases known as glycolytic
      enzymopathies, but is unique for its severe patient neuropathology and early
      mortality. The disease is caused by missense mutations and dysfunction in the
      glycolytic enzyme, TPI. Previous studies have detailed structural and catalytic
      changes elicited by disease-associated TPI substitutions, and samples of patient
      erythrocytes have yielded insight into patient hemolytic anemia; however, the
      neuropathophysiology of this disease remains a mystery. This study combines
      structural, biochemical, and genetic approaches to demonstrate that perturbations
      of the TPI dimer interface are sufficient to elicit TPI deficiency
      neuropathogenesis. The present study demonstrates that neurologic dysfunction
      resulting from TPI deficiency is characterized by synaptic vesicle dysfunction,
      and can be attenuated with catalytically inactive TPI. Collectively, our findings
      are the first to identify, to our knowledge, a functional synaptic defect in TPI
      deficiency derived from molecular changes in the TPI dimer interface. 

PMID- 27031112
TI  - Correction: Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed
      by Metabolomic Profiling of Tuberculosis Patients.

PMID- 27031111
TI  - Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium
      tuberculosis Ligands to MAIT Cells.
AB  - Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway
      and other mucosal tissues, have Th1 effector capacity positioning them to play a
      critical role in the early immune response to intracellular pathogens, including
      Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule
      that presents vitamin B metabolites to MAIT cells. The mechanisms for loading
      these ubiquitous small molecules are likely to be tightly regulated to prevent
      inappropriate MAIT cell activation. To define the intracellular localization of
      MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen
      presenting cells. We found that MR1 localized to endosomes and was translocated
      to the cell surface upon addition of 6-formyl pterin (6-FP). To understand the
      mechanisms by which MR1 antigens are presented, we used a lentiviral shRNA screen
      to identify trafficking molecules that are required for the presentation of Mtb
      antigen to HLA-diverse T cells. We identified Stx18, VAMP4, and Rab6 as
      trafficking molecules regulating MR1-dependent MAIT cell recognition of Mtb
      infected cells. Stx18 but not VAMP4 or Rab6 knockdown also resulted in decreased
      6-FP-dependent surface translocation of MR1 suggesting distinct pathways for
      loading of exogenous ligands and intracellular mycobacterially-derived ligands.
      We postulate that endosome-mediated trafficking of MR1 allows for selective
      sampling of the intracellular environment. 

PMID- 27031113
TI  - All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH,
      Detemir, and Glargine.
AB  - BACKGROUND: Insulin therapy in type 2 diabetes may increase mortality and cancer
      incidence, but the impact of different types of basal insulins on these endpoints
      is unclear. Compared to the traditional NPH insulin, the newer, longer-acting
      insulin analogues detemir and glargine have shown benefits in randomized
      controlled trials. Whether these advantages translate into lower mortality among
      users in real life is unknown. OBJECTIVE: To estimate the differences in all
      cause and cause-specific mortality rates between new users of basal insulins in a
      population-based study in Finland. METHODS: 23 751 individuals aged >=40 with
      type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified
      from national registers, with comprehensive data for mortality, causes of death,
      and background variables. Propensity score matching was performed on
      characteristics. Follow-up time was up to 4 years (median 1.7 years). RESULTS:
      2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause
      mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69)
      for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among
      detemir users. Compared to NPH, the mortality risk for both cardiovascular causes
      as well as cancer were also significantly lower for glargine, and especially for
      detemir in adjusted analysis. Furthermore, the results were robust in various
      sensitivity analyses. CONCLUSION: In real clinical practice, mortality was
      substantially higher among users of NPH insulin as compared to insulins detemir
      or glargine. Considering the large number of patients who require insulin
      therapy, this difference in risk may have major clinical and public health
      implications. Due to limitations of the observational study design, further
      investigation using an interventional study design is warranted.

PMID- 27031115
TI  - Red to Near-Infrared Isoindole BODIPY Fluorophores: Synthesis, Crystal
      Structures, and Spectroscopic and Electrochemical Properties.
AB  - A series of high-performance fluorophores named isoindole boron dipyrromethenes
      (BODIPYs) containing either symmetrical or unsymmetrical alkyl substitution
      patterns on pyrrole rings were synthesized by an efficient process and were
      characterized by X-ray diffraction and spectroscopic and electrochemical
      analyses. Most of these dyes show strong, sharp absorption and bright
      fluorescence emission in the red to near-infrared (NIR) region (up to 805 nm in
      acetonitrile). Pyrrolic alkyl substitutions lead to increases in the HOMO and
      LUMO energy levels and an overall decrease in the energy band gaps of the dye.
      Among the 23 isoindole BODIPY dyes synthesized, solvent-dependent fluorescence
      emission and lifetime decay were only observed for those containing a 3-methyl
      substituent on the uncoordinated pyrrole ring, whereas little variation in the
      fluorescence intensity was observed for the rest of the dyes upon changing the
      polarity of the solvent. These resultant dyes can be further functionalized via
      the Knoevenagel condensation on the alpha-methyl substituent of the chromophore
      to install a variety of functionalities, including a dimethylamine group
      demonstrated in this work. This dimethylamine-functionalized isoindole BODIPY
      shows weak fluorescence at 805 nm in acetonitrile and a ratiometric "turn-on" NIR
      fluorescence response to decreasing pH.

PMID- 27031114
TI  - The Fifth Domain of Beta 2 Glycoprotein I Protects from Natural IgM Mediated
      Cardiac Ischaemia Reperfusion Injury.
AB  - Reperfusion after a period of ischemia results in reperfusion injury (IRI) which
      involves activation of the inflammatory cascade. In cardiac IRI, IgM natural
      antibodies (NAb) play a prominent role through binding to altered neoepitopes
      expressed on damaged cells. Beta 2 Glycoprotein I (beta2GPI) is a plasma protein
      that binds to neoepitopes on damaged cells including anionic phospholipids
      through its highly conserved Domain V. Domain I of beta2GPI binds circulating IgM
      NAbs and may provide a link between the innate immune system, IgM NAb binding and
      cardiac IRI. This study was undertaken to investigate the role of Beta2GPI and
      its Domain V in cardiac IRI using wild-type (WT), Rag-1 -/- and beta2GPI
      deficient mice. Compared with control, treatment with Domain V prior to cardiac
      IRI prevented binding of endogenous beta2GPI to post-ischemic myocardium and
      resulted in smaller myocardial infarction size in both WT and beta2GPI deficient
      mice. Domain V treatment in WT mice also resulted in less neutrophil
      infiltration, less apoptosis and improved ejection fraction at 24 h. Rag-1 -/-
      antibody deficient mice reconstituted with IgM NAbs confirmed that Domain V
      prevented IgM NAb induced cardiac IRI. Domain V remained equally effective when
      delivered at the time of reperfusion which has therapeutic clinical
      relevance.Based upon this study Domain V may function as a universal inhibitor of
      IgM NAb binding in the setting of cardiac IRI, which offers promise as a new
      therapeutic strategy in the treatment of cardiac IRI. 

PMID- 27031118
TI  - Characterising receptive language processing in schizophrenia using word and
      sentence tasks.
AB  - INTRODUCTION: Language dysfunction is proposed to relate to the speech
      disturbances in schizophrenia, which are more commonly referred to as formal
      thought disorder (FTD). Presently, language production deficits in schizophrenia
      are better characterised than language comprehension difficulties. This study
      thus aimed to examine three aspects of language comprehension in schizophrenia:
      (1) the role of lexical processing, (2) meaning attribution for words and
      sentences, and (3) the relationship between comprehension and production.
      METHODS: Fifty-seven schizophrenia/schizoaffective disorder patients and 48
      healthy controls completed a clinical assessment and three language tasks
      assessing word recognition, synonym identification, and sentence comprehension.
      Poorer patient performance was expected on the latter two tasks. RESULTS:
      Recognition of word form was not impaired in schizophrenia, indicating intact
      lexical processing. Whereas single-word synonym identification was not
      significantly impaired, there was a tendency to attribute word meanings based on
      phonological similarity with increasing FTD severity. Importantly, there was a
      significant sentence comprehension deficit for processing deep structure, which
      correlated with FTD severity. CONCLUSIONS: These findings established a receptive
      language deficit in schizophrenia at the syntactic level. There was also evidence
      for a relationship between some aspects of language comprehension and speech
      production/FTD. Apart from indicating language as another mechanism in FTD
      aetiology, the data also suggest that remediating language comprehension problems
      may be an avenue to pursue in alleviating FTD symptomatology.

PMID- 27031119
TI  - Who "jumps to conclusions"? A comprehensive assessment of probabilistic reasoning
      in psychosis following traumatic brain injury (PFTBI), and comparison with TBI,
      schizophrenia, and nonclinical controls.
AB  - INTRODUCTION: The "jumping to conclusions" (JTC) bias has received significant
      attention in the schizophrenia and delusion literature as an important aspect of
      cognition characterising psychosis. The JTC bias has not been explored in
      psychosis following traumatic brain injury (PFTBI). METHODS: JTC was investigated
      in 10 patients with PFTBI using the beads task (ratios 85:15 and 60:40).
      Probabilistic predictions, draws-to-decision, self-rated decision confidence, and
      JTC bias were recorded. Responses from 10 patients with traumatic brain injury
      (TBI), 23 patients with schizophrenia, and 23 nonclinical controls were compared.
      Relationships were explored between draws-to-decision and current intelligence
      quotient, affective state, executive function, delusions (severity and type), and
      illness chronicity (duration). RESULTS: Groups were comparable on JTC measures.
      Delusion severity and type were not related to draws-to-decision for either
      trial. In the entire sample, executive function (reduced mental flexibility) was
      significantly related to more draws-to-decision on the 60:40 ratio trial.
      CONCLUSIONS: We found no evidence for an elevated JTC bias in patients with PFTBI
      or TBI alone. The influence of executive dysfunction should be considered by
      future studies using the beads tasks in patient populations. These findings need
      to be replicated in larger PFTBI and TBI samples.

PMID- 27031120
TI  - Vein imaging laser reduces bruising in bruise-prone botulinum toxin injected
      patients.
AB  - BACKGROUND: Injection-related bruising is a common complication of many
      injectable treatments including facial injections of botulinum toxin (BTX) for
      aesthetic use. OBJECTIVE: We have investigated the use of a vein imaging laser
      (VIL) to observe otherwise non-visible subcutaneous blood vessels in 40 patients
      who had a history of bruising with past BTX injections to the face during the
      previous 12 months. METHODS: Over a 4-month period 40 patients, who previously
      had developed bruising after injectable BTX to the face, were treated with
      further BTX to the same areas as previously, but using a VIL during the
      injections. Patients were evaluated for their severity of bruising. RESULTS: 40
      patients out of 2400 patients had experienced bruising with a severity score
      total of 92 (mean per patient 2.3) with BTX injections before VIL use. On
      injection using the VIL 6 of the 40 patients had bruising with severity score
      total of 7 (mean 1.16). CONCLUSION: The use of a VIL significantly reduced the
      frequency and severity of bruising associated with BTX injections.

PMID- 27031121
TI  - Patients with prolonged effect of succinylcholine or mivacurium had novel
      mutations in the butyrylcholinesterase gene.
AB  - INTRODUCTION: Mutations in the butyrylcholinesterase enzyme (BChE) can result in
      prolonged duration of action of the neuromuscular blocking agents,
      succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low
      BChE activity can cause extensively prolonged apnoea during general anaesthesia
      when these drugs are used. The aim of this study was to describe novel mutations
      in the butyrylcholinesterase gene (BCHE) in patients who have experienced
      prolonged duration of action of mivacurium or succinylcholine. METHODS: The
      Danish Cholinesterase Research Unit registers patients with prolonged duration of
      action to succinylcholine and mivacurium. Patients were studied if they had
      equivocal phenotypes on the basis of BChE activity, biochemical inhibitor
      reactions and with pedigree if possible. Complete nucleotide sequencing was
      performed to describe the genotype and pedigree was used to separate the alleles.
      Multiple sequence alignment of BChE was performed for comparison with other
      species. RESULTS: Genotyping indicated seven novel mutations in the BCHE (I373T,
      G467S, W518R, L184S, V421A, M462I and R577H). CONCLUSION: We have found seven new
      variants of the BCHE, which seem to reduce the activity of BChE in patients
      undergoing anaesthesia involving succinylcholine or mivacurium.

PMID- 27031122
TI  - Targeting Senescent Cells: Possible Implications for Delaying Skin Aging: A Mini
      Review.
AB  - Senescent cells are induced by a wide variety of stimuli. They accumulate in
      several tissues during aging, including the skin. Senescent cells secrete
      proinflammatory cytokines, chemokines, growth factors, and proteases, a
      phenomenon called senescence-associated secretory phenotype (SASP), which are
      thought to contribute to the functional decline of the skin as a consequence of
      aging. Due to the potential negative effects of the SASP in aged organisms, drugs
      that selectively target senescent cells represent an intriguing therapeutic
      strategy to delay aging and age-related diseases. Here, we review studies on the
      role of senescent cells in the skin, with particular emphasis on the age-related
      mechanisms and phenotypes associated with excessive accumulation of cellular
      senescence. We discuss the aberrant behavior of senescent cells in aging and how
      the different signaling pathways associated with survival and secretion of
      senescent cells can be engaged for the development of targeted therapies.

PMID- 27031123
TI  - Long-Lasting Stent Placement in an Elderly Advanced Ovarian Cancer Patient.
AB  - BACKGROUND: Ovarian cancer is usually diagnosed at an advanced stage, most often
      co-occurring with malignant bowel obstruction. Affected patients are generally in
      poor physical condition, and it is important to manage the bowel obstruction to
      improve quality of life. CASE REPORT: We present the case of a 75-year-old woman
      who underwent a left hemicolectomy for an ovarian carcinoma with bowel
      obstruction. 3 years after hemicolectomy, the patient presented with an extrinsic
      anastomotic substenosis. A self-expanding metal stent was placed which remained
      in place for 7 years, rendering other invasive surgical treatments unnecessary.
      CONCLUSION: The placement of a long-lasting stent is an important option in
      patients with bowel obstruction subsequent to recurrent ovarian cancer, since
      this provides a viable alternative to surgery and increases patients' quality of
      life.

PMID- 27031124
TI  - Fabrication of Inkjet-Printed Gold Nanostar Patterns with Photothermal Properties
      on Paper Substrate.
AB  - Inkjet printing technology has brought significant advances in patterning various
      functional materials that can meet important challenges in personalized medical
      treatments. Indeed, patterning of photothermal active anisotropic gold
      nanoparticles is particularly promising for the development of low-cost tools for
      localized photothermal therapy. In the present work, stable inks containing
      PEGylated gold nanostars (GNSs) were prepared and inkjet printed on a pigment
      coated paper substrate. A significant photothermal effect (DeltaT ? 20  degrees
      C) of the printed patterns was observed under near infrared (NIR) excitation of
      the localized surface plasmon resonance (LSPR) of the GNS with low laser
      intensity (I ? 0.2 W/cm(2)). Besides the pronounced photothermal effect, we also
      demonstrated, as an additional valuable effect, the release of a model
      fluorescent thiol-terminated Bodipy dye (BDP-SH) from the printed gold surface,
      both under bulk heating and NIR irradiation. These preliminary results suggest
      the way of the development of a new class of low-cost, disposable, and smart
      devices for localized thermal treatments combined with temperature-triggered drug
      release. 

PMID- 27031125
TI  - Ocular Myasthenia Gravis: Toward a Risk of Generalization Score and Sample Size
      Calculation for a Randomized Controlled Trial of Disease Modification.
AB  - BACKGROUND: There is currently no prognostic test to determine the risk of
      developing generalized myasthenia gravis (GMG) risk in patients who first present
      with ocular disease. Most studies that report risk factors are flawed by the
      inclusion of patients on immunosuppression, which is likely to reduce the risk.
      OBJECTIVE: To create a prognostic score to predict the risk of GMG. METHODS:
      Multicenter retrospective cohort of patients with ocular myasthenia gravis for
      minimum 3 months, untreated with immunosuppression for minimum 2 years or until
      GMG onset. RESULTS: One hundred one (57 female) patients were included, with
      median follow-up of 8.4 years (2-42) from disease onset. Thirty-one developed GMG
      at median of 1.31 years (3.5 months-20.2 years); 19 occurred within 2 years.
      Univariable logistic regression analysis produced 3 significant predictors (P <
      0.10), adjusted odds ratios in a multivariable logistic model (chi P = 0.01) with
      multiple imputations for missing data: seropositivity, 5.64 (95% CI, 1.45-21.97);
      presence of 1 or more comorbidities including autoimmune disorders, 6.49 (95% CI,
      0.78-53.90); thymic hyperplasia, 5.41 (95% CI, 0.39-75.43). Prognostic score was
      derived from the coefficients of the logistic model: sum of the points (1 point
      for the presence of each of the above predictive factors), classified "low risk"
      if <=1 and "high risk" if >=2. Predicted probabilities were 0.07 (SD, 0.03) for
      low risk and 0.39 (SD, 0.09) for high risk. Negative predictive value was 91%
      (95% CI, 79-98), positive predictive value was 38% (95% CI, 23-54), sensitivity
      was 79% (95% CI, 54-94), specificity was 63% (95% CI, 50-74), area under receiver
      operating characteristic curve was 0.74 (95% CI, 0.64-0.85). CONCLUSIONS: In this
      preliminary study, we have shown by proof of principle that it is possible to
      stratify risk of GMG: an approach that may allow us to better counsel patients at
      diagnosis, complement decision-making, and move us toward addressing the question
      of modifying GMG risk in high-risk patients. Furthermore, the effect of
      comorbidities is novel and demands further elucidation.

PMID- 27031126
TI  - Optic Neuropathy and Stroke Secondary to Invasive Aspergillus in an
      Immunocompetent Patient.
AB  - Angioinvasive aspergillosis is an aggressive fungal infection that is potentially
      life threatening without prompt treatment. Optic nerve involvement of Aspergillus
      can mimic optic neuritis commonly seen in demyelinating and other inflammatory
      conditions. Treatment of Aspergillus infection with steroids may worsen the
      clinical course. We describe a unique case of disseminated central nervous system
      aspergillosis, initially presenting as an optic neuropathy, with subsequent
      stroke in multiple vascular territories.

PMID- 27031127
TI  - Might dolutegravir be part of a functional cure for HIV?
AB  - Antiretroviral therapy (ART) has greatly decreased HIV-related morbidity and
      mortality. However, HIV can establish viral reservoirs that evade both the immune
      system and ART. Dolutegravir (DTG) is a second-generation integrase strand
      transfer inhibitor (INSTI) related to the first-generation INSTIs raltegravir
      (RAL) and elvitegravir (EVG). DTG shows a higher genetic barrier to the
      development of HIV-1 resistance than RAL and EVG. More interestingly, clinical
      resistance mutations to DTG in treatment-naive patients have not been observed to
      date. This review summarizes recent studies on strategies toward a cure for HIV,
      explores resistance profiles of DTG, and discusses how DTG might help in finding
      a functional cure for HIV. 

PMID- 27031163
TI  - Cutinisation of tomato fruit epidermis: Structural and morphological details.
AB  - In tomato, the ovary is covered with a thin, electron-dense and uniform cuticle.
      The first 10 d after anthesis are critical in the cutinisation of the outer
      epidermal wall. During this period, singular cytoplasmic domains have been
      identified in the epidermal cells which seem to be involved in lipid
      biosynthesis. Moreover, the inner side of the procuticle showed a globular
      structure with vesicle-like particles of different size that seemed to migrate
      from the cytoplasm to the procuticle. These electron-dense particles are
      postulated to play an important role in early cutin synthesis. 

PMID- 27031164
TI  - Novel therapeutics in metastatic colorectal cancer: molecular insights and
      pharmacogenomic implications.
AB  - Although the survival of metastatic colorectal cancer (mCRC) patients has
      improved five-fold over the last century, CRC remains a significant global health
      burden. Impressive strides have been made in identifying new regimens, employing
      maintenance strategies to limit treatment toxicities, and combining
      multidisciplinary approaches to achieve cure in oligometastatic disease. Attempts
      at personalized integration of targeted agents have been limited by the ability
      to identify molecularly enriched patient populations most likely to benefit. In
      this review, we discuss novel therapeutics and regimens recently approved and in
      development for mCRC. In addition, we discuss using older agents in novel
      combination and maintenance strategies, and highlight evidence for implementing
      pharmacogenomic data and non-invasive monitoring into the personalized management
      of mCRC patients. 

PMID- 27031165
TI  - Effective microorganism - X attenuates circulating superoxide dismutase following
      an acute bout of intermittent running in hot, humid conditions.
AB  - This study determined the effectiveness of antioxidant supplementation on high
      intensity exercise-heat stress. Six males completed a high-intensity running
      protocol twice in temperate conditions (TEMP; 20.4 degrees C), and twice in hot
      conditions (HOT; 34.7 degrees C). Trials were completed following7 days
      supplementation with 70 ml.day(-1) effective microorganism-X (EM-X; TEMPEMX or
      HOTEMX) or placebo (TEMPPLA or HOTPLA). Plasma extracellular Hsp72 (eHsp72) and
      superoxide dismutase (SOD) were measured by ELISA. eHsp72 and SOD increased pre
      post exercise (p < 0.001), with greater eHsp72 (p < 0.001) increases observed in
      HOT (+1.5 ng.ml(-1)) compared to TEMP (+0.8 ng.ml(-1)). EM-X did not influence
      eHsp72 (p > 0.05). Greater (p < 0.001) SOD increases were observed in HOT (+0.22
      U.ml(-1)) versus TEMP (+0.10 U.ml(-1)) with SOD reduced in HOTEMX versus HOTPLA
      (p = 0.001). Physiological and perceptual responses were all greater (p < 0.001)
      in HOT versus TEMP conditions, with no difference followed EM-X (p > 0.05). EM-X
      supplementation attenuated the SOD increases following HOT, potentiating its
      application as an ergogenic aid to ameliorate oxidative stress. 

PMID- 27031166
TI  - Oncologists' non-verbal behavior and analog patients' recall of information.
AB  - Background Information in oncological consultations is often excessive. Those
      patients who better recall information are more satisfied, less anxious and more
      adherent. Optimal recall may be enhanced by the oncologist's non-verbal
      communication. We tested the influence of three non-verbal behaviors, i.e. eye
      contact, body posture and smiling, on patients' recall of information and
      perceived friendliness of the oncologist. Moreover, the influence of patient
      characteristics on recall was examined, both directly or as a moderator of non
      verbal communication. Material and methods Non-verbal communication of an
      oncologist was experimentally varied using video vignettes. In total 194 breast
      cancer patients/survivors and healthy women participated as 'analog patients',
      viewing a randomly selected video version while imagining themselves in the role
      of the patient. Directly after viewing, they evaluated the oncologist. From 24 to
      48 hours later, participants' passive recall, i.e. recognition, and free recall
      of information provided by the oncologist were assessed. Results Participants'
      recognition was higher if the oncologist maintained more consistent eye contact
      (beta = 0.17). More eye contact and smiling led to a perception of the oncologist
      as more friendly. Body posture and smiling did not significantly influence
      recall. Older age predicted significantly worse recognition (beta = -0.28) and
      free recall (beta = -0.34) of information. Conclusion Oncologists may be able to
      facilitate their patients' recall functioning through consistent eye contact.
      This seems particularly relevant for older patients, whose recall is
      significantly worse. These findings can be used in training, focused on how to
      maintain eye contact while managing computer tasks. 

PMID- 27031167
TI  - The relationship between aggression, empathy skills and serum oxytocin levels in
      male children and adolescents with attention deficit and hyperactivity disorder.
AB  - Although attention deficit and hyperactivity disorder (ADHD) are recognized as
      neurodevelopmental disorders characterized by impairment in executive functions,
      impairments in social functioning are often accompanied by ADHD. Oxytocin (OT)
      has been investigated in a number of psychiatric disorders owing to its effects
      on social interactions. The aim of this study was to determine the relationship
      between aggression, empathy and OT levels in children with ADHD. Forty male
      patients with ADHD, ranging in age from 7 to 18 years, and 40 healthy age-matched
      and sex-matched individuals were included in this study. The patients and healthy
      controls filled in the Buss-Perry Aggression Questionnaire and Bryant's Empathy
      Index for Children and Adolescents; the Reading the Mind in the Eyes test was
      then completed. Blood samples were collected for OT at the beginning of the
      study. Lower serum OT levels were observed in patients with ADHD compared with
      the healthy controls. Moreover, there was a negative correlation between serum OT
      level and aggression scores and a positive correlation between the serum OT level
      and empathy scores in patients with ADHD. We conclude that OT may play a role in
      aggression and empathy skills, affecting the social life of those with ADHD.

PMID- 27031168
TI  - Spirosoma aerophilum sp. nov., isolated from an air sample.
AB  - A rod-shaped, yellow, Gram-stain-negative, non-flagellated, aerobic bacterium,
      designated 5516J-17T, was isolated from an air sample collected from Jeju Island,
      Republic of Korea. It grew in the temperature range of 10-37  degrees C (optimum
      28-30  degrees C), pH 6.0-11.0 (optimum, pH 7.0) and 0-1 % NaCl (w/v).
      Phylogenetic trees generated using 16S rRNA gene sequences revealed that strain
      5516J-17T belongs to the genus Spirosoma, showing 96.9 % sequence similarity to
      the most closely related species, Spirosoma linguale DSM 74T. The cellular fatty
      acids comprised large amounts (>10 % of total fatty acids) of summed feature 3
      (C16:1omega7c and/or C16:1omega6c) and C16:1omega5c, and moderate amounts (5-10 %
      of total fatty acids) of iso-C17:0 3-OH, iso-C15:0 and C16:0. The DNA G+C content
      was 55.7 mol % and MK-7 was the predominant isoprenoid quinone. Polar lipids were
      phosphatidylethanolamine, two unknown aminophospholipids, one unknown aminolipid
      and one unknown lipid. On the basis of this phenotypic and polyphasic taxonomy
      study, it is suggested that strain 5516J-17T represents a novel species within
      the genus Spirosoma, with the proposed name Spirosoma aerophilum. The type strain
      is 5516J-17T (= KACC 17323T = DSM 28388T = JCM 19950T). 

PMID- 27031169
TI  - Streptomyces indoligenes sp. nov., isolated from rhizosphere soil of Populus
      euphratica.
AB  - A novel actinobacterium, designated TRM 43006T, was isolated from the rhizosphere
      soil of Populus euphratica in Xinjiang Province, north-west China. Phylogenetic
      and phenotypic analysis demonstrated that strain TRM 43006T belongs to the genus
      Streptomyces. The strain was aerobic and Gram-stain-positive; the aerial mycelium
      branched monopodially, forming chains of arthrospores. The spores were oval to
      cylindrical with smooth surfaces. The whole-cell sugar pattern of strain TRM
      43006T consisted of xylose, mannitol, galactose and ribose. The menaquinones were
      MK-9(H6), MK-9(H8) and MK-9(H10). The polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol,
      phosphatidylinositol mannosides and four unknown phospholipids. Major fatty acids
      were iso-C16 : 0, iso-C16 : 1, iso-C14 : 0 and anteiso-C15 : 0. The G+C content
      of the genomic DNA was 69.0 mol%. Comparative 16S rRNA gene sequence analysis
      indicated that strain TRM 43006T was phylogenetically most closely related to
      Streptomyces roseolilacinus NBRC 12815T (98.6 % similarity) and
      Streptomycessudanensis SD 504T (98.3 %); however, DNA-DNA hybridization studies
      between S. roseolilacinus NBRC 12815T, S. sudanensis SD 504T and TRM 43006T
      showed only 30.28 and 30.65  % relatedness, respectively. Based on the evidence
      from this polyphasic study, strain TRM 43006T represents a novel species of the
      genus Streptomyces, for which the name Streptomyces indoligenes sp. nov. is
      proposed. The type strain is TRM 43006T (=KCTC 39611T=CCTCC AA 2015010T). 

PMID- 27031170
TI  - Characterization of the non-coding control region of polyomavirus KI isolated
      from nasopharyngeal samples from patients with respiratory symptoms or infection
      and from blood from healthy blood donors in Norway.
AB  - Seroepidemiological studies showed that the human polyomavirus KI (KIPyV) is
      common in the human population, with age-specific seroprevalence ranging from 40
      90 %. Genome epidemiological analyses demonstrated that KIPyV DNA is
      predominantly found in respiratory tract samples of immunocompromised individuals
      and children suffering from respiratory diseases, but viral sequences have also
      been detected in brain, tonsil, lymphoid tissue studies, plasma, blood and
      faeces. Little is known about the sequence variation in the non-coding control
      region of KIPyV variants residing in different sites of the human body and
      whether specific strains dominate in certain parts of the world. In this study,
      we sequenced the non-coding control region (NCCR) of naturally occurring KIPyV
      variants in nasopharyngeal samples from patients with respiratory symptoms or
      infection and in blood from healthy donors in Norway. In total 86 sequences were
      obtained, 44 of which were identical to the original isolated Stockholm 60
      variant. The remaining NCCRs contained one or several mutations, none of them
      previously reported. The same mutations were detected in NCCRs amplified from
      blood and nasopharyngeal samples. Some patients had different variants in their
      specimens. Transient transfection studies in HEK293 cells with a luciferase
      reporter plasmid demonstrated that some single mutations had a significant effect
      on the relative early and late promoter strength compared with the Stockholm 60
      promoter. The effect of the NCCR mutations on viral replication and possible
      virulence properties remains to be established.

PMID- 27031171
TI  - Effects of Subclinical Mycobacterium chelonae Infections on Fecundity and Embryo
      Survival in Zebrafish.
AB  - Mycobacteriosis is the second most common infectious disease in zebrafish
      research colonies, and most often this is caused by Mycobacterium chelonae. The
      infection is characterized by multiple granulomas in the kidney, coelomic cavity,
      particularly the ovary. However, most fish still appear clinically normal.
      Developmental genetics remain a primary area of research with the zebrafish
      model, and hence, an important use of adult zebrafish is as brood fish to produce
      embryos. We investigated the effects of experimentally induced M. chelonae
      infections on fecundity. A total of 480 5D wild-type zebrafish were divided into
      four groups: controls, males infected, females infected, and both sexes. Exposed
      fish developed high prevalence of infection, including many females with ovarian
      infections. Fish were then first subjected to four separate group spawns with
      four replicate tanks/group. Then, a third of the fish were subjected to pairwise
      spawns, representing 20 pairs/group, and then the pairs were evaluated by
      histopathology. Overall, the group and pairwise spawns resulted numerous eggs and
      viable embryos. However, we found no statistical correlations between infection
      status and number of eggs or viability. In contrast to Egg Associated
      Inflammation and Fibroplasia, lesions in infected ovaries were more localized,
      with large regions of the ovary appearing normal.

PMID- 27031172
TI  - Eliminating the Term Primary Care "Provider": Consequences of Language for the
      Future of Primary Care.

PMID- 27031173
TI  - Multistep Reaction Based De Novo Drug Design: Generating Synthetically Feasible
      Design Ideas.
AB  - We describe a "multistep reaction driven" evolutionary algorithm approach to de
      novo molecular design. Structures generated by the approach include a proposed
      synthesis path intended to aid the chemist in assessing the synthetic feasibility
      of the ideas that are generated. The methodology is independent of how the design
      ideas are scored, allowing multicriteria drug design to address multiple issues
      including activity at one or more pharmacological targets, selectivity, physical
      and ADME properties, and off target liabilities; the methods are compatible with
      common computer-aided drug discovery "scoring" methodologies such as 2D- and 3D
      ligand similarity, docking, desirability functions based on physiochemical
      properties, and/or predictions from 2D/3D QSAR or machine learning models and
      combinations thereof to be used to guide design. We have performed experiments to
      assess the extent to which known drug space can be covered by our approach. Using
      a library of 88 generic reactions and a database of ~20 000 reactants, we find
      that our methods can identify "close" analogs for ~50% of the known small
      molecule drugs with molecular weight less than 300. To assess the quality of the
      in silico generated synthetic pathways, synthesis chemists were asked to rate the
      viability of synthesis pathways: both "real" and in silico generated. In silico
      reaction schemes generated by our methods were rated as very plausible with
      scores similar to known literature synthesis schemes.

PMID- 27031174
TI  - Entropy Driven Self-Assembly in Charged Lock-Key Particles.
AB  - In this work we study the lock-key model successfully used in supramolecular
      chemistry and particles self-assembly and gain further insight into the infinite
      diluted limit of the lock and key, depletant mediated, effective attraction. We
      discuss the depletant forces and entropy approaches to self-assembly and give
      details on the different contributions to the net force for a charged lock and
      key pair immersed in a solvent plus a primitive model electrolyte. We show a
      strong correlation of the force components behavior and the underlying processes
      of co-ion and solvent release from the cavity. In addition, we put into context
      the universal behavior observed for the energy-distance curves when changing the
      lock and key to solvent size ratio. Basically, we now show that this behavior is
      not always achieved and depends on the particular system geometry. Finally, we
      present a qualitative good agreement with experiments when changing the
      electrolyte concentration, valence, and cavity-key size ratio.

PMID- 27031175
TI  - Healing the damaged mesangium in nodular glomerulosclerosis using mesenchymal
      stem cells (MSCs): Expectations and challenges.
AB  - It has been shown experimentally that mesenchymal stem cells (MSCs) can be
      delivered to the mesangium in some conditions such as amyloidosis to clear debris
      and foreign material, and eventually transform into functional mesangial cells
      (MCs) and change the altered mesangial areas into normal collagen IV-rich matrix.
      A more challenging situation is when the matrix is rich in abnormal extracellular
      matrix proteins, especially those difficult to destroy such as tenascin, and, as
      a result, assumes a nodular appearance - what is known in pathology jargon as
      nodular glomerulosclerosis. MSCs find it difficult to dispose of the altered
      mesangial constituents, an initial step required for mesangial repair to occur
      successfully. The ability of MSCs to repair damaged mesangium represents a novel
      therapeutic intervention to reverse mesangial injury and is potentially a
      powerful and unique approach to prevent progression ending in end-stage renal
      disease (ESRD). This review will highlight progress that has been made in
      glomerular, and more specifically mesangial, repair, and will address future
      expectations and challenges to be confronted as the use of MSCs continues to be
      explored as a potential application for clinical practice. 

PMID- 27031176
TI  - Exosomes in human atherosclerosis: An ultrastructural analysis study.
AB  - Cell-to-cell communication, or signaling, is absolutely essential in
      orchestrating the activities of cells in multicellular organisms, to grow,
      develop, detect environmental changes and compensate for them in an internal,
      coordinated fashion. In the last few years, a considerable amount of new data
      have demonstrated the occurrence of a sophisticated intercellular signaling
      pathway based on the release of specialized vesicular structures, called
      exosomes, whose secretion appears to be regulated by various natural and
      experimental stimuli, physiological states, and disease processes. In the
      cardiovascular system, the study of exosomes is still in its infancy. Here, we
      aim to provide the first ultrastructural evidence for the presence of exosomes in
      human atherosclerotic plaque. We demonstrate by means of transmission electron
      microscopy that both lesional smooth muscle cells and endothelial cells are able
      to generate these membraneous microvesicles within specific compartments of the
      cell, called multivesicular bodies. Notably, in our series no signs of apoptosis
      have been detected in vascular cells secreting exosomes and no evidence of
      calcification has been observed associated with these structures in the
      extracellular space. Our results suggest the possible existence of a new
      mechanism of intercellular communication in the plaque milieu. 

PMID- 27031177
TI  - Unusual lamellar calcifications in two rare cases of splenic aneurysms associated
      with fibromuscular dysplasia.
AB  - Fibromuscular dysplasia (FMD) of the splenic artery is a rare underdiagnosed
      condition. Here, we report two cases of FMD affecting the splenic artery: one
      alone and one concomitantly with the renal artery. Histology revealed
      fibromuscular thickening of the media layer alternating with a circumferential
      calcification of the whole artery thickness. Ultrastructurally, FMD showed matrix
      vesicles and dense bodies in the extracellular matrix. A diagnosis of FMD with
      calcification was made. This is the first report to document circumferential
      lamellar calcifications alternating with the more typical fibrotic medial areas
      in the rare FMD localized to splenic artery. 

PMID- 27031178
TI  - Essential role of ultrastructural examination for spindle cell oncocytoma: Case
      report of a rare neoplasm and review of the literature.
AB  - Spindle cell oncocytoma (SCO) is an extremely rare neoplasm of the sellar region
      recognized as a distinct benign histopathological subtype of pituitary tumors in
      the 2007 World Health Organization classification of tumors of the central
      nervous system. The morphology of its neoplastic cells (spindle cells and
      granular eosinophilic cytoplasm) is common to several other lesions so that
      immunohistochemistry, together with ultrastructural examination, becomes
      essential in solving this differential diagnosis. Despite being labeled as
      benign, recurrence is described. Herein, we report a case of SCO in a 77-year-old
      man and discuss the diagnostic difficulties, ultrastructural aspects, and
      prognostic factors. 

PMID- 27031179
TI  - A dynamical approach to non-adiabatic electron transfers at the bio-inorganic
      interface.
AB  - A methodology is proposed to investigate electron transfer reactions between
      redox-active biomolecular systems (e.g. a protein) and inorganic surfaces. The
      whole system is modelled at the atomistic level using classical molecular
      dynamics - making an extensive sampling of the system's configurations possible -
      and the energies associated with the redox-active complex reduction are
      calculated using a hybrid quantum/classical approach along the molecular dynamics
      trajectory. The non-adiabaticity is introduced a posteriori using a Monte Carlo
      approach based on the Landau-Zener theory extended to treat a metal surface. This
      approach thus allows us to investigate the role of the energy fluctuations,
      determined by the dynamical evolution of the system, as well as the role of non
      adiabaticity in affecting the kinetic rate of the electron transfer reaction.
      Most notably, it allows us to investigate the two contributions separately, hence
      achieving a detailed picture of the mechanisms that determine the rate. The
      analysis of the system configurations also allows us to relate the estimated
      electronic coupling to the structural and dynamic properties of the system. As a
      test case, the methodology is here applied to study the electron transfer
      reaction between cytochrome c and a gold surface. The results obtained explain
      the different electron transfer rates experimentally measured for two different
      concentrations of proteins on the electrode surface. 

PMID- 27031180
TI  - Optimization models for degrouping population data.
AB  - In certain countries population data are available in grouped form only, usually
      as quinquennial age groups plus a large open-ended range for the elderly.
      However, official statistics call for data by individual age since many
      statistical operations, such as the calculation of demographic indicators,
      require the use of ungrouped population data. In this paper a number of
      mathematical models are proposed which, starting from population data given in
      age groups, enable these ranges to be degrouped into age-specific population
      values without leaving a fractional part. Unlike other existing procedures for
      disaggregating demographic data, ours makes it possible to process several years'
      data simultaneously in a coherent way, and provides accurate results
      longitudinally as well as transversally. This procedure is also shown to be
      helpful in dealing with degrouped population data affected by noise, such as
      those affected by the age-heaping phenomenon.

PMID- 27031181
TI  - Short-term tibolone does not interfere with endothelial function: a double
      blinded, randomized, controlled trial.
AB  - Objective To evaluate the effect of short-term hormone replacement therapy with
      tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women,
      using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a
      randomized, double-blinded, placebo-controlled study. A total of 100 healthy
      postmenopausal women were randomly allocated to receive tibolone (n = 50) or
      placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was
      performed before and after the use of tibolone and placebo. Results A total of 31
      women completed the study in the tibolone group, and 32 women completed the study
      in the control group. The results of the FMD measurements obtained from the women
      in the two groups before treatment were similar (0.018 and 0.091, for tibolone
      and placebo, p = 0.57). The values of the FMD in women who used tibolone and
      placebo, before and after the treatment, were similar in both groups. The numbers
      of women who presented an increase in the values of the FMD in both groups were
      also similar. Conclusion Our results demonstrate that the administration of 2.5
      mg tibolone to healthy postmenopausal women for 28 days does not promote
      endothelial-dependent vasodilation, measured by FMD of the brachial artery. 

PMID- 27031182
TI  - Assessment of sit-to-stand movement in nonspecific low back pain: a comparison
      study for psychometric properties of field-based and laboratory-based methods.
AB  - One of the most difficult tasks associated with the management of nonspecific low
      back pain (LBP) is its clinical assessment. Objective functional methods have
      been developed for assessment. However, few studies have used daily activities
      such as sit-to-stand (STS). The aim was to compare the psychometric properties of
      two commonly used STS assessment methods. A test-retest reliability study design
      was used. Participants with nonspecific LBP performed the 30-s chair stand test
      (30CST) and the STS test in Balance Master, which measures weight transfer,
      rising index and centre of gravity sway velocity. The same tests were reperformed
      after 48-72 h. The intraclass correlation coefficient (ICC), standard error of
      measurement (SEM), minimal detectable change and coefficient of variation were
      calculated to compare the reliability. The correlations between the tests, the
      Oswestry Disability Index and pain intensity were examined for validation. The
      30CST had very high intrarater reliability (ICC=0.94). The variables of STS test
      in Balance Master had moderate intrarater reliability (ICC=0.62-0.69). There were
      significant correlations between the 30CST, Oswestry Disability Index and pain
      intensity at activity (P<0.01). The rising index was the only one variable that
      was significantly correlated with pain intensity at activity (P<0.05). The 30CST
      as the field-based method to measure STS movement was better than the laboratory
      based method in terms of their psychometric properties. Moreover, the 30CST was
      associated with disability and pain related to LBP. The 30CST is a simple, cheap,
      less time consuming and psychometrically appropriate method to use in individuals
      with nonspecific LBP. 

PMID- 27031183
TI  - Energy transfer dynamics and kinetics of elementary processes (promoted) by gas
      phase CO2 -N2 collisions: Selectivity control by the anisotropy of the
      interaction.
AB  - In this work, we exploit a new formulation of the potential energy and of the
      related computational procedures, which embodies the coupling between the intra
      and intermolecular components, to characterize possible propensities of the
      collision dynamics in energy transfer processes of interest for simulation and
      control of phenomena occurring in a variety of equilibrium and nonequilibrium
      environments. The investigation reported in the paper focuses on the prototype
      CO2 -N2 system, whose intramolecular component of the interaction is modeled in
      terms of a many body expansion while the intermolecular component is modeled in
      terms of a recently developed bonds-as-interacting-molecular-centers' approach.
      The main advantage of this formulation of the potential energy surface is that of
      being (a) truly full dimensional (i.e., all the variations of the coordinates
      associated with the molecular vibrations and rotations on the geometrical and
      electronic structure of the monomers, are explicitly taken into account without
      freezing any bonds or angles), (b) more flexible than other usual formulations of
      the interaction and (c) well suited for fitting procedures better adhering to
      accurate ab initio data and sensitive to experimental arrangement dependent
      information. Specific attention has been given to the fact that a variation of
      vibrational and rotational energy has a higher (both qualitative and
      quantitative) impact on the energy transfer when a more accurate formulation of
      the intermolecular interaction (with respect to that obtained when using rigid
      monomers) is adopted. This makes the potential energy surface better suited for
      the kinetic modeling of gaseous mixtures in plasma, combustion and atmospheric
      chemistry computational applications. (c) 2016 Wiley Periodicals, Inc.

PMID- 27031184
TI  - Two-stage sample-to-answer system based on nucleic acid amplification approach
      for detection of malaria parasites.
AB  - Rapid, early, and accurate diagnosis of malaria is essential for effective
      disease management and surveillance, and can reduce morbidity and mortality
      associated with the disease. Although significant advances have been achieved for
      the diagnosis of malaria, these technologies are still far from ideal, being time
      consuming, complex and poorly sensitive as well as requiring separate assays for
      sample processing and detection. Therefore, the development of a fast and
      sensitive method that can integrate sample processing with detection of malarial
      infection is desirable. Here, we report a two-stage sample-to-answer system based
      on nucleic acid amplification approach for detection of malaria parasites. It
      combines the Dimethyl adipimidate (DMA)/Thin film Sample processing (DTS)
      technique as a first stage and the Mach-Zehnder Interferometer-Isothermal solid
      phase DNA Amplification (MZI-IDA) sensing technique as a second stage. The system
      can extract DNA from malarial parasites using DTS technique in a closed system,
      not only reducing sample loss and contamination, but also facilitating the
      multiplexed malarial DNA detection using the fast and accurate MZI-IDA technique.
      Here, we demonstrated that this system can deliver results within 60min
      (including sample processing, amplification and detection) with high sensitivity
      (<1 parasite MUL(-1)) in a label-free and real-time manner. The developed system
      would be of great potential for better diagnosis of malaria in low-resource
      settings. 

PMID- 27031185
TI  - Facile fabrication of an electrochemical aptasensor based on magnetic electrode
      by using streptavidin modified magnetic beads for sensitive and specific
      detection of Hg(2.).
AB  - In this work, a novel electrochemical aptasensor was developed for sensitive and
      specific detection of Hg(2+) based on thymine-Hg(2+)-thymine (T-Hg(2+)-T)
      structure via application of thionine (Th) as indicator signal. For the
      fabrication of the aptasensor, streptavidin modified magnetic beads (Fe3O4-SA)
      was firmly immobilized onto the magnetic glassy carbon electrode (MGCE) benefited
      from its magnetic character. Then biotin labeled T-riched single stranded DNA
      (Bio-ssDNA) connected with Fe3O4-SA specifically and steadily because of the
      specific binding capacity between streptavidin and biotin. The stable structure
      of T-Hg(2+)-T formed in the present of Hg(2+) provided convenience for the
      intercalation of Th. The detection of Hg(2+) was achieved by recording the
      differential pulse voltammetry (DPV) signal of Th. Under optimal experimental
      conditions, the linear range of the fabricated electrochemical aptasensor was 1
      200nmol/L, with a detection limit of 0.33nmol/L. Furthermore, the proposed
      aptasensor may find a potential application for the detection of Hg(2+) in real
      water sample analysis. 

PMID- 27031186
TI  - Bioengineering bacteriophages to enhance the sensitivity of phage amplification
      based paper fluidic detection of bacteria.
AB  - Bacteriophage (phage) amplification is an attractive method for the detection of
      bacteria due to a narrow phage-host specificity, short amplification times, and
      the phages' ability to differentiate between viable and non-viable bacterial
      cells. The next step in phage-based bacteria detection is leveraging
      bioengineered phages to create low-cost, rapid, and easy-to-use detection
      platforms such as lateral flow assays. Our work establishes the proof-of-concept
      for the use of bioengineered T7 phage strains to increase the sensitivity of
      phage amplification-based lateral flow assays. We have demonstrated a greater
      than 10-fold increase in sensitivity using a phage-based protein reporter,
      maltose-binding protein, over the detection of replicated T7 phage viron itself,
      and a greater then 100-fold increase in sensitivity using a phage-based enzymatic
      reporter, alkaline phosphatase. This increase in sensitivity enabled us to detect
      10(3)CFU/mL of Escherichia coli in broth after 7h, and by adding a filter
      concentration step, the ability to detect a regulatory relevant E. coli
      concentration of 100CFU/100mL in inoculated river water after 9h, where the
      current standard requires days for results. The combination of the paper fluidic
      format with phage-based detection provides a platform for the development of
      novel diagnostics that are sensitive, rapid, and easy to use. 

PMID- 27031187
TI  - Polythiophene nanofilms for sensitive fluorescence detection of viruses in
      drinking water.
AB  - Molecular imprints of the tobacco necrosis virus (TNV) have been formed within
      polythiophene nanofilms with an approximate thickness of 200nm. These films have
      been electrochemically deposited onto conducting Au surfaces. Upon rebinding, the
      TNV-polythiophene complex changes the fluorescence intensity of the nanofilm. The
      fluorescence intensity at 410nm was observed to be proportional to the
      concentration of viruses in the range of 0.1-10ngL(-1) (0.15-15pg) with the lower
      calculated detection limit of 2.29ngL(-1) (3.4pg). The intensity of the
      fluorescence emission is not affected by the thickness of the polythiophene film
      and the nature of TNV specific binding sites. Kinetic data analyses showed that
      the nanofilm responds to TNV within 2min; and cross-selectivity studies with
      tobacco mosaic virus (TMV) showed an excellent specificity for the targeted TNV.
      These binding experiments demonstrate the potential of fluorescence emission for
      the specific, label free and rapid detection of viruses using nanofilm sensors.
      Taking into account the lower limit of detection, the fluorescence sensing
      reported here is reliable, simple to perform, rapid, cost-effective and offers a
      sensitive analytical method for virus detection in water resources. 

PMID- 27031188
TI  - Turn-on near-infrared electrochemiluminescence sensing of thrombin based on
      resonance energy transfer between CdTe/CdS coresmall/shellthick quantum dots and
      gold nanorods.
AB  - Here we designed a near-infrared electrochemiluminescence (NECL) aptasensor for
      turn-on ultrasensitive determination of thrombin. It was based on the ECL
      resonance energy transfer (ECL-RET) of CdTe/CdS coresmall/shellthick quantum dots
      (QDs) to gold nanorods (AuNRs). AuNRs which functioned as ECL acceptors were
      assembled onto CdTe/CdS film by DNA hybridization between aptamers and their
      complementary oligonucleotides. In the absence of thrombin, the NECL of QDs was
      quenched as a result of the ECL-RET of QDs to AuNRs. In the presence of thrombin,
      the NECL of the system was "turned on" because thrombin can replace the AuNRs
      onto the QDs film, owing to the specific aptamer-protein affinity interactions.
      In this way, the increment of ECL intensity and the concentration of thrombin
      showed a logarithmic linear correlation in the range of 100 aM to 10 fM with a
      detection limit of 31 aM (S/N=3). Importantly, the developed aptasensor was
      successfully applied to thrombin sensing in real serum samples. 

PMID- 27031189
TI  - Practical selection methods for rat and mouse round spermatids without DNA
      staining by flow cytometric cell sorting.
AB  - Round spermatid injection (ROSI) into unfertilized oocytes enables a male with a
      severe spermatogenesis disorder to have children. One limitation of the
      application of this technique in the clinic is the identification and isolation
      of round spermatids from testis tissue. Here we developed an efficient and simple
      method to isolate rodent haploid round spermatids using flow cytometric cell
      sorting, based on DNA content (stained with Hoechst 33342 or Dye Cycle Violet) or
      by cell diameter and granularity (forward and side scatter). ROSI was performed
      with round spermatids selected by flow cytometry, and we obtained healthy
      offspring from unstained cells. This non-invasive method could therefore be an
      effective option for breeding domestic animals and human male infertility
      treatment. Mol. Reprod. Dev. 83: 488-496, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27031190
TI  - Methyl tetra-O-acetyl-alpha-D-glucopyranuronate: crystal structure and influence
      on the crystallisation of the beta anomer.
AB  - Methyl tetra-O-acetyl-beta-D-glucopyranuronate (1) and methyl tetra-O-acetyl
      alpha-D-glucopyranuronate (3) were isolated as crystalline solids and their
      crystal structures were obtained. That of the beta anomer (1) was the same as
      that reported by Root et al., while anomer (3) was found to crystallise in the
      orthorhombic space group P212121 with two independent molecules in the asymmetric
      unit. No other crystal forms were found for either compound upon
      recrystallisation from a range of solvents. The alpha anomer (3) was found to be
      an impurity in initially precipitated batches of beta-anomer (1) in quantities
      <3%; however, it was possible to remove the alpha impurity either by
      recrystallisation or by efficient washing, i.e. the alpha anomer is not
      incorporated inside the beta anomer crystals. The beta anomer (1) was found to
      grow as prisms or needles elongated in the a crystallographic direction in the
      absence of the alpha impurity, while the presence of the alpha anomer (3)
      enhanced this elongation.

PMID- 27031191
TI  - Synthesis and x-ray crystallographic analysis of 4,6-di-O-acetyl-2,3-dideoxy
      alpha-D-threo-hexopyranosyl cyanide.
AB  - The glycopyranosyl cyanide 4,6-di-O-acetyl-2,3-dideoxy-alpha-D-threo
      hexopyranosyl cyanide has been synthesized from tri-O-acetyl-D-galactal by
      reaction with trimethylsilyl cyanide in the presence of boron trifluoride diethyl
      etherate followed by catalytic hydrogenation. The synthesis provides the alpha
      anomer stereoselectively, the structure of which was assigned based on 2D NMR
      techniques and x-ray crystallography.

PMID- 27031192
TI  - Adnexal masses requiring reoperation in women with previous hysterectomy with or
      without adnexectomy.
AB  - OBJECTIVES: To characterize the etiologies of adnexal masses requiring
      reoperation in women with prior hysterectomy and to compare incidence and
      pathology of these masses based upon whether total, partial or no adnexectomy was
      performed at time of hysterectomy. In addition, the average time interval between
      hysterectomy and reoperation for a pelvic mass is ascertained. STUDY DESIGN: A
      single-institution, retrospective review spanning 10 years. Using pertinent ICD-9
      and CPT codes, women with a history of hysterectomy who underwent a subsequent
      surgery for an adnexal or pelvic mass were identified. RESULTS: Over ten years,
      250 women returned for gynecologic surgery due to a pelvic mass after prior
      hysterectomy. Most had undergone hysterectomy only (76%). 64.8% of these women
      had masses of ovarian origin, 12.4% were tubal in origin, 20% of masses involved
      both the ovary and tube and a small proportion arose from non-gynecologic
      processes. 18% of these women had a malignancy; 80% were ovarian and 6.7%
      originated from the fallopian tube. Patients having had a prior hysterectomy and
      bilateral salpingectomy returned soonest (p<0.0001) and patients with malignant
      masses returned after the longest time intervals (HR 0.41, p<0.0001).
      CONCLUSIONS: The majority of adnexal masses requiring reoperation after
      hysterectomy are gynecologic in origin, benign, and arise from the ovary. Women
      returning with malignant masses after hysterectomy present after longer time
      intervals.

PMID- 27031193
TI  - Theoretical Studies of Oxygen Reactivity of Free-Standing and Supported Boron
      Doped Graphene.
AB  - Graphene inertness towards chemical reactivity can be considered as an accepted
      postulate by the research community. This limit has been recently overcome by
      chemically and physically modifying graphene through non-metal doping or
      interfacing with acceptor/donor materials (metals or semiconductors). As a
      result, outstanding performances as catalytic, electrocatalytic, and
      photocatalytic material have been observed. In this critical Review we report
      computational work performed, by our group, on the reactivity of free-standing,
      metal- and semiconductor-supported B-doped graphene towards oxygen, which is at
      the basis of extremely important energy-related chemical processes, such as the
      oxygen reduction reaction. It appears that a combination of doping and
      interfacing approaches for the activation of graphene can open unconventional and
      unprecedented reaction paths, thus boosting the potential of modified graphene in
      many chemical applications.

PMID- 27031194
TI  - Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study
      in the French Pharmacovigilance Database.
AB  - BACKGROUND: Inhibitors of dipeptidyl peptidase (DPP)-IV have been suspected in
      the onset of bullous pemphigoid for several years now. However, comparative
      studies assessing the link between DPP-IV inhibitor exposure and bullous
      pemphigoid have not yet been performed. OBJECTIVES: To detect, from the French
      Pharmacovigilance Database (FPVD), a signal of risk of bullous pemphigoid during
      DPP-IV inhibitor exposure by comparative study. METHODS: All spontaneous reports
      of DPP-IV inhibitor-related bullous pemphigoid recorded in the FPVD between April
      2008 and August 2014 were described. We conducted disproportionality analyses
      (case-noncase method) to assess the link between DPP-IV inhibitors and bullous
      pemphigoid, calculating reporting odds ratios (RORs). We also compared DPP-IV
      inhibitor-induced bullous pemphigoid reports rated per million defined daily
      doses dispensed during the study period. RESULTS: Among 217 331 spontaneous
      adverse drug reaction reports registered in the FPVD, 1297 involved DPP-IV
      inhibitors. Among these observations, 42 were bullous pemphigoid (vildagliptin, n
      = 31; sitagliptin, n = 10; saxagliptin, n = 1). The ROR for pooled DPP-IV
      inhibitors was 67.5 [95% confidence interval (CI) 47.1-96.9]. Disproportionality
      was also observed for each DPP-IV inhibitor: vildagliptin (ROR 225.3, 95% CI
      148.9-340.9), sitagliptin (ROR 17.0, 95% CI 8.9-32.5) and saxagliptin (ROR 16.5,
      95% CI 2.3-119.1). Analyses adjusted on dispensing data led to similar results.
      CONCLUSIONS: These data confirm a strong signal for an increased risk of bullous
      pemphigoid during DPP-IV inhibitor exposure. This adverse drug reaction is
      observed for each DPP-IV inhibitor, suggesting a class effect. The signal was
      higher with vildagliptin than with the other DPP-IV inhibitors.

PMID- 27031195
TI  - Effects of perfluorooctane sulfonate on the conformation and activity of bovine
      serum albumin.
AB  - Perfluorooctane sulfonate (PFOS) is among the most prominent contaminates in
      human serum and has been reported to possess potential toxicity to the human
      body. In this study, the effects of PFOS on the conformation and activity of
      bovine serum albumin (BSA) were investigated in vitro. The results indicated that
      the binding interaction of PFOS with BSA destroyed the tertiary and secondary
      structures of protein with the loss of alpha-helix structure and the increasing
      of hydrophobic microenvironment of the Trp or Tyr residues. During the thermal
      denaturation protein, PFOS increases the protein stability of BSA. The proportion
      of alpha-helix decreased on increasing the PFOS concentration and the
      microenvironment of the Trp or Tyr residues becomes more hydrophobic. The results
      from molecular modeling indicated that BSA had not only one possible binding site
      to bind with PFOS by the polar interaction, hydrogen bonds and hydrophobic
      forces. In addition, the BSA relative activities were decreased with the increase
      of PFOS concentration. Such loss of BSA activity in the presence of PFOS
      indicated that one of the binding sites in BSA is located in subdomain IIIA,
      which is in good agreement with the fluorescence spectroscopic experiments and
      molecular modeling results. This study offers a comprehensive picture of the
      interactions of PFOS with serum albumin and provides insights into the
      toxicological effect of perfluoroalkylated substances. 

PMID- 27031196
TI  - [Digital medicine--a new challenge].

PMID- 27031197
TI  - [Cognitive disorders in elder patients with chronic kidney disease].
AB  - The prevalence of cognitive disorders in CKD-patients is high. A screening of
      dementia is easy to perform. There are increasing possibilities of cognitive
      training in dialysis patients. 

PMID- 27031198
TI  - [Systemic therapy of metastatic renal cell carcinoma].
AB  - In metastatic ccRCC , the treatment options in 1st line treatment are still the
      tyrosinkinase inhibitors (TKI) pazopanib and sunitinib, for patients with low or
      intermediate risk additionally IFNalpha/bevacizumab and for high risk patients
      the mTOR inhibitor temsirolimus. In 2nd line following cytokine therapy, axitinib
      or pazopanib and following TKI /VEGF directed therapy axitinib or everolimus may
      be administered. New upcoming agents in RCC are the PD1 antibody nivolumab and
      the multikinase inhibitor Cabozantinib, which both showed an OS advantage
      compared to everolimus. After marketing authorization in Europe, these agents
      should therefore be preferred in 2nd and 3rd line therapy. Further agents are
      under investigation. 

PMID- 27031199
TI  - [Acute bacterial meningitis: an update].
AB  - In patients with clinically suspected acute bacterial meningitis, physicians
      should aim for a quick diagnostic workup including lumbar puncture. Cerebral
      imaging before lumbar puncture is only indicated in patients with focal
      neurologic deficits, impaired consciousness, epileptic seizures within one week
      before presentation or a history of immunosuppression. One important prognostic
      factor is a rapid initiation of an empiric antibiotic therapy which should best
      be started within 1 hour after hospital admission. 

PMID- 27031200
TI  - [Intensive care and legislation].

PMID- 27031201
TI  - [Medical and interventional treatment of right heart failure].
AB  - New pharmacological approaches are introduced for the treatment of chronic right
      heart failure which aim at reduced mortality. Riociguat is a new drug for the
      treatment of chronic thrombembolic pulmonary hypertension. Transcatheter valve
      interventions are established for treatment of pulmonary valve diseases and
      introduced as promising upcoming therapeutic options for tricuspid regurgitation.
      The management of acute right heart failure is supported by the miniaturization
      of mechanical circulatory support systems with percutaneous cannulation
      applicable in terms of "Bridge to Recovery" and "Bridge to Decision" concepts and
      effective long-term support, respectively.

PMID- 27031202
TI  - [Acute kidney injury: update 2016].
AB  - Acute kidney injury is still defined by the functional parameters diuresis and
      serum creatinine. New biomarkers can be sensible additions for the detection of
      pathogenesis and prognosis. Risk stratification is also very useful for
      identification of patients at risk for the development of acute kidney injury.
      This is of increased importance as usual therapeutic treatments are rare and long
      term effects are devastating.

PMID- 27031203
TI  - [Community-acquired pneumonia].
AB  - Community acquired pneumonia (CAP) is an infection with a limited spectrum of
      pathogens. Pneumonias acquired in a hospital or under immunoincompetence are
      being treated according to different algorithms. The concept of health care
      associated pneumonia (HCAP) is discarted. It is not capable to predict a high
      probability of multiresistant pathogens. 

PMID- 27031204
TI  - [Polymyalgia rheumatic--what's new?].
AB  - Ultrasound, MRI and PET-CT reveal a typical anatomical distribution of
      inflammation in the shoulder and pelvic girdle. MRI and PET-CT may additionally
      show inflammation along the spine. New classification criteria include age >= 50
      years, elevated CRP and / or ESR, and shoulder girdle pain as well as two
      alternative algorithms with or without ultrasound. The algorithm with ultrasound
      is more specific but equally sensitive than the other algorithm. According to new
      recommendations on management diagnosis should be definitely established. Lab
      tests need to be considered as well as comorbidities. A starting dose of 12.5-25
      mg / d prednisone - equivalent is recommended, followed by a dose reduction to 10
      mg / d within 4-8 weeks. Afterwards the dose should be reduced by 1 mg every 4
      weeks. Methotrexate might be added in patients with significant risks and
      comorbidities. Follow-up visits should occur every 4-8 weeks during the first
      year. 

PMID- 27031205
TI  - [Non-alcoholic fatty liver disease--What's new].
AB  - Clinical guidelines are essential in implementing and maintaining nationwide
      stage-specific diagnostic and therapeutic standards. In 2015, the first German
      expert consensus guideline defined the evidence for epidemiology, pathogenesis,
      diagnosis and treatment of non-alcoholic fatty liver diseases in adults and
      children. The German S2k-guideline used an approved development process with de
      novo literature research since 2010, international guideline adaptation, or good
      clinical practice. Other recent evidence-based national guidelines and current
      references were included. 

PMID- 27031206
TI  - [56-year old man with reduced performance].

PMID- 27031208
TI  - [Periodic Repolarization Dynamics--innovative strategies for preventing sudden
      death].
AB  - Sudden cardiac death (SCD) is the most common single cause of death in the
      industrialized world. Survivors of acute myocardial infarction (MI) are at
      increased risk of death. The vast majority of deaths occur in post-MI patients
      with preserved left ventricular ejection fraction (LVEF) for whom no prophylactic
      strategies exist. Periodic repolarization dynamics (PRD) is a novel
      electrocardiographic phenomenon that refers to low frequency (< 0.1 Hz)
      modulations of cardiac repolarization, most likely linked to sympathetic
      activity. Increased PRD is a strong and independent predictor of mortality after
      acute MI. PRD assessment allows to identify a new high risk group of post-MI
      patients with preserved LVEF (35-50 %) who have the same mortality risk as
      patients with LVEF <= 35 %. Future studies are needed to test the efficacy of
      preventive strategies in this new high risk group. 

PMID- 27031207
TI  - [Acute anterior myocardial infarction after rituximab].
AB  - HISTORY: A 36-year-old man with a history of PR3-ANCA positive granulomatosis
      with polyangiitis presented with chest pain at the emergency department. Due to
      his underlying disease, he was treated with Rituximab in regular intervals. The
      last Rituximab infusion was admitted one day before presentation. INVESTIGATION:
      The ECG showed marked ST elevation in V1-V4. DIAGNOSIS, TREATMENT AND COURSE:
      After the diagnosis of an acute anterior myocardial infarction, the patient was
      prepared for acute percutaneous coronary intervention. During transport to the
      cardiac catheterization laboratory, he suffered a cardiac arrest due to
      ventricular fibrillation. After successful resuscitation, the cardiac
      catheterization showed no evidence of relevant coronary stenosis. Because of
      suspected coronary spasm of left anterior descending artery the therapy was
      extended with a calcium channel blocker. A single chamber cardiac defibrillator
      was implanted for secondary prevention. CONCLUSION: Acute coronary syndrome is a
      possible side effect of rituximab therapy. The reported case emphasizes a
      correlation between Rituximab therapy and cardiac event.

PMID- 27031209
TI  - Multilayered Graphene Hydrogel Membranes for Guided Bone Regeneration.
AB  - A multilayered graphene hydrogel (MGH) membrane is used as an excellent barrier
      membrane for guided bone regeneration. The unique multilayered nanostructure of
      the MGH membrane results in improved material properties, which benefits protein
      adsorption, cell adhesion, and apatite deposition, and allows higher quality and
      fast bone regeneration. 

PMID- 27031210
TI  - Clinical Application of High-Resolution Computed Tomographic Imaging Features of
      Community-Acquired Pneumonia.
AB  - BACKGROUND: This article discusses the value of high-resolution computed
      tomography (HRCT) in the diagnosis and treatment of pulmonary infections. Lung
      infection caused by pathogens is an important cause of death. Traditional methods
      to treat lung infection involved empirical antibiotic therapy. Thin-slice CT
      scanning is widely used in the clinical setting, and HRCT scan can very clearly
      show alveolar and bronchiolar involvement of infection. MATERIAL/METHODS: In
      total, 178 patients with community-acquired pneumonia (CAP) were enrolled. All
      the patients underwent CT scan, qualified sputum, and blood samples for culture
      or immunological biochemical tests. CT imaging features, pathogenic bacteria, and
      treatment results were used for statistical analysis. RESULTS: In 77 patients
      with lobar consolidation, the rate of detection was 43.26% (77/178), and in 101
      patients with lobular pneumonia it was 56.74% (101/178). In 51 patients,
      pathogenic bacteria were detected (28.65%, 51/178). Sixteen of 33 patients
      detected with bacteria had cavities (48.5%, 16/33) and 35 of 145 patients
      detected with bacteria had no cavities (24.1%, 35/145). The difference between
      the 2 groups was statistically significant (chi(2)=7.795, P=0.005). According to
      the pathogenic bacteria, 38 patients were cured (74.51%, 38/51), and according to
      the CT imaging features 81 patients were cured (71.05%, 81/114). No statistically
      significant difference was found between them (chi(2)=0.209, P=0.647).
      CONCLUSIONS: Treatment effect of CAP based on HRCT findings is not inferior to
      treatment effect guided by microbial characterization.

PMID- 27031211
TI  - Synthesis, characterization and biological evaluation of benzothiazoles and
      tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and
      inhibitors of the insulin releasing process.
AB  - A series of 1,3-benzothiazoles (series I) and 4,5,6,7-tetrahydro-1,3
      benzothiazoles (series II) bearing an urea or a thiourea moiety at the 2-position
      were synthesized and tested as myorelaxants and inhibitors of insulin secretion.
      Several compounds (i.e. 13u and 13v) from series I showed a marked myorelaxant
      activity. Benzothiazoles bearing a strong electron withdrawing group (NO2, CN) at
      the 6-position and an alkyl group linked to the urea or the thiourea function at
      the 2-position were found to be the most potent compounds. The weak vasorelaxant
      activity of series II compounds evidenced the necessity of the presence of a
      complete aromatic heterocyclic system. The myorelaxant activity of some active
      compounds was reduced when measured on aorta rings precontracted by 80 mM KCl or
      by 30 mM KCl in the presence of 10 MUM glibenclamide, suggesting the involvement
      of KATP channels in the vasorelaxant effect. Some compounds of series I tested on
      rat pancreatic islets provoked a marked inhibition of insulin secretion, among
      which 13a exhibited a clear tissue selectivity for pancreatic beta-cells. 

PMID- 27031212
TI  - Cell-penetrating conjugates of pentaglutamylated methotrexate as potential
      anticancer drugs against resistant tumor cells.
AB  - The emerging resistance of tumor cells against methotrexate (MTX) is one of the
      major limitations of the MTX treatment of tumorous diseases. The disturbance in
      the polyglutamation which is a main step in the mechanism of methotrexate action
      is often the reason of the resistance. Delivery of polyglutamylated MTX into
      cells may evade the mechanisms that are responsible for drug resistance. In this
      study conjugates of methotrexate and its pentaglutamylated derivatives with cell
      penetrating peptides - penetratin and octaarginine - were investigated. The
      cellular-uptake and in vitro cytostatic activity of conjugates were examined on
      breast cancer cell cultures (MDA-MB-231 as resistant and MCF-7 as sensitive cell
      culture). These cell cultures showed very different behaviour towards the
      conjugates. Although the presence of pentaglutamyl moiety significantly decreased
      the internalisation of conjugates, some of them were significantly active in
      vitro. All of the conjugates were able to penetrate in some extent into both cell
      types, but only the conjugates of penetratin showed in vitro cytostatic activity.
      The most effective conjugates were the MTX-Glu5-Penetratin(desMet) and MTX-Glu5
      GFLG-Penetratin(desMet). The latter was effective on both cell cultures while the
      former was active only on the resistant tumor cells. Our results suggest that the
      translocation of polyglutamylated MTX may be a new way to treat sensitive and
      more importantly resistant tumors. While both penetratin and octaarginine
      peptides were successfully used to deliver several kinds of cargos earlier in our
      case the activity of penetratin conjugates was more pronounced. 

PMID- 27031213
TI  - Discovery of a ring-opened derivative of 3-n-butylphthalide bearing NO/H2S
      donating moieties as a potential anti-ischemic stroke agent.
AB  - To search for novel anti-ischemic stroke agents with higher potency than a known
      drug 3-n-butylphthalide (NBP), a series of ring-opened derivatives of NBP bearing
      both nitric oxide (NO) and hydrogen sulfide (H2S)-donating moieties (NO/H2S-NBP)
      (8a-8o) were designed, synthesized, and biologically evaluated. The most active
      compound 8d was more potent than NBP and the corresponding H2S-NBP 10 or NO-NBP
      13 in inhibition of the ADP-induced platelet aggregation in vitro. In addition,
      8d produced moderate levels of NO and H2S, which could be beneficial for
      improving cardiovascular and cerebral circulation. More importantly, in a rat
      model of transient focal cerebral ischemia, oral treatment with 8d improved
      neurobehavioral function, reduced the infarct brain size and brain-water content,
      and enhanced the levels of brain antioxidant SOD, GSH and GSH-Px but diminished
      the level of oxidant MDA. These protective effects of 8d against the
      ischemia/reperfusion (I/R)-related brain damage were greater than that of NBP,
      suggesting that 8d may be a promising agent for further investigation. 

PMID- 27031214
TI  - Novel chromone and xanthone derivatives: Synthesis and ROS/RNS scavenging
      activities.
AB  - Chromones and xanthones are oxygen-containing heterocyclic compounds acknowledged
      by their antioxidant properties. In an effort to develop novel agents with
      improved activity, a series of compounds belonging to these chemical classes were
      prepared. Their syntheses involve the condensation of appropriate 2-methyl-4H
      chromen-4-ones, obtained via Baker-Venkataraman rearrangement, with (E)-3-(3,4
      dimethoxyphenyl)acrylaldehyde to provide the corresponding 2-[(1E,3E)-4-(3,4
      dimethoxyphenyl)buta-1,3-dien-1-yl]-4H-chromen-4-ones. Subsequent
      electrocyclization and oxidation of these compounds led to the synthesis of 1
      aryl-9H-xanthen-9-ones. After cleavage of the protecting groups, hydroxylated
      chromones and xanthones were assessed as scavenging agents against both reactive
      oxygen species (ROS) [superoxide radical (O2(*-)), hydrogen peroxide (H2O2),
      hypochlorous acid (HOCl), singlet oxygen ((1)O2), and peroxyl radical (ROO(*))]
      and reactive nitrogen species (RNS) [nitric oxide ((*)NO) and peroxynitrite anion
      (ONOO(-))]. Generally, all the tested new hydroxylated chromones and xanthones
      exhibited scavenger effects dependent on the concentration, with IC50 values
      found in the micromolar range. Some of them were shown to have improved
      scavenging activity when compared with previously reported analogues, allowing
      the inference of preliminary conclusions on the structure-activity relationship. 

PMID- 27031215
TI  - Synthesis of triazoloquinazolinone based compounds as tubulin polymerization
      inhibitors and vascular disrupting agents.
AB  - A series of 1-phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5-ones designed as
      conformationally restricted CA-4 analogues, were tested for their tubulin
      polymerization and growth inhibitory activities. The 3-hydroxy-4-methoxy
      derivatives 11d and 12d are potent inhibitors of tubulin assembly but only the N
      methylated amid counterpart 12d possesses potent anticancer activity in a large
      panel of cancer cell lines. Upon treatment with compound 12d, remarkable cell
      shape changes as cell migration and tube formation were elicited in HUVECs,
      consistent with vasculature damaging activity. 

PMID- 27031216
TI  - Transfer of SAR information from hypotensive indazole to indole derivatives
      acting at alpha-adrenergic receptors: In vitro and in vivo studies.
AB  - In a search for novel antihypertensive drugs we applied scaffold hopping from the
      previously described alpha1-adrenergic receptor antagonists, 1-[(imidazolin-2
      yl)methyl]indazoles. The aim was to investigate whether the alpha-adrenergic
      properties of the indazole core were transferable to the indole core. The newly
      obtained 1-[(imidazolin-2-yl)methyl]indole analogues were screened in vitro for
      their binding affinities for alpha1-and alpha2-adrenoceptors, which allowed the
      identification of the target-based SAR transfer (T_SAR transfer) as well as
      structure-based SAR transfer (S_SAR transfer) events. However, when screened in
      vivo with use of anaesthetized male Wistar rats, the new indole ligands showed a
      different hemodynamic profile than expected. Instead of the immediate hypotensive
      effect characteristic of peripheral vasodilatator alpha1 blockers, a biphasic
      effect was observed, reminiscent of clonidine-like centrally acting
      antihypertensive agents. This was supported by subsequent in vitro functional
      studies in [(35)S]GTPgammaS binding assay, where the indole analogues displayed
      partial agonist properties at alpha2-adrenergic receptors. Since no correlation
      was found between the in vitro binding to alpha-adrenoceptors and the in vivo
      hemodynamic effects of the two series of indazole and indole bioisosteric
      compounds, in a search for new imidazoline-containing adrenergic drugs, the
      structure-based SAR transfer information obtained from in vitro binding studies
      should be treated with caution.

PMID- 27031217
TI  - Site-Specific Conjugation of Peptides and Proteins via Rebridging of Disulfide
      Bonds Using the Thiol-Yne Coupling Reaction.
AB  - Herein, we describe an extension of our previously reported photomediated
      disulfide rebridging methodology to the conjugation of peptides and proteins. The
      methodology proved to be reproducible with various alkynes and different
      peptides. This study includes the first rebridging of the disulfide bond of a
      peptide through a thiol-yne reaction with a cyclooctyne. In all cases, the
      rebridging was proven by MS analyses and confirmed by the absence of olefinic
      protons on (1)H NMR spectra of the resulting products. Finally, this one-pot
      reduction thiol-yne conjugation was successfully applied to an antibody Fab
      fragment with a promising conversion, which set a good ground for the future
      syntheses of new protein and antibody conjugates. 

PMID- 27031218
TI  - The two faces of reactive oxygen species (ROS) in adipocyte function and
      dysfunction.
AB  - White adipose tissue (WAT) is actively involved in the regulation of whole-body
      energy homeostasis via storage/release of lipids and adipokine secretion. Current
      research links WAT dysfunction to the development of metabolic syndrome (MetS)
      and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients
      prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte
      differentiation. An assumed link between excess levels of reactive oxygen species
      (ROS), WAT dysfunction and T2D has been discussed controversially. While
      oxidative stress conditions have conclusively been detected in WAT of T2D
      patients and related animal models, clinical trials with antioxidants failed to
      prevent T2D or to improve glucose homeostasis. Furthermore, animal studies
      yielded inconsistent results regarding the role of oxidative stress in the
      development of diabetes. Here, we discuss the contribution of ROS to the
      (patho)physiology of adipocyte function and differentiation, with particular
      emphasis on sources and nutritional modulators of adipocyte ROS and their
      functions in signaling mechanisms controlling adipogenesis and functions of
      mature fat cells. We propose a concept of ROS balance that is required for normal
      functioning of WAT. We explain how both excessive and diminished levels of ROS,
      e.g. resulting from over supplementation with antioxidants, contribute to WAT
      dysfunction and subsequently insulin resistance.

PMID- 27031219
TI  - Binary tomography reconstruction from few projections with Total Variation
      regularization for bone microstructure studies.
AB  - Discrete tomography refers to a class of reconstruction methods adapted to
      discrete-valued images. Many different approaches have been investigated to
      address the binary case, when a two-phase object is considered. This
      reconstruction problem is very important in medical or material applications
      where it is crucial to reduce the number of projections. In this paper, we
      address the problem of binary image reconstruction for X-ray CT imaging from a
      small number of projections. We propose a TV (Total Variation) regularization
      approach and compare the results obtained with or without an additional box
      convex constraint. The schemes are applied to a simple disk image and to more
      complex bone cross-sections for various noise levels. The minimization of the
      regularization functional is performed with the state-of-the-art ADMM (Alternate
      Direction Minimization Method) algorithm. The methods perform equally well on a
      simple disk image. The additional box convex constraints improves the
      reconstruction results for complex structures with fine details. 

PMID- 27031220
TI  - Announcement: National Public Health Week--April 4-10, 2016.
AB  - Every year since 1995, the American Public Health Association has led the
      observation of National Public Health Week in the United States during the first
      full week of April. The goal of National Public Health Week is to acknowledge
      contributions made by public health and to raise awareness of issues important to
      improving the nation's health. This year's observance focuses on building a
      nation of safe and healthy communities. Additional information about this year's
      observance is available at http://www.nphw.org. 

PMID- 27031223
TI  - ERRATUM: Cystic fibrosis on the African continent.

PMID- 27031224
TI  - Followers are not followed: Observed group interactions modulate subsequent
      social attention.
AB  - We asked whether previous observations of group interactions modulate subsequent
      social attention episodes. Participants first completed a learning phase with 2
      conditions. In the "leader" condition 1 of 3 identities turned her gaze first,
      followed by the 2 other faces. In the "follower" condition, 1 of the identities
      turned her gaze after the 2 other faces had first shifted their gaze. Thus,
      participants observed that some individuals were consistently leaders and others
      followers of others' attention. In the test phase, the faces of leaders and
      followers were presented in a gaze cueing paradigm. Remarkably, the followers did
      not elicit gaze cueing. Our data demonstrate that individuals who do not guide
      group attention in exploring the environment are ineffective social attention
      directors in later encounters. Thus, the role played in previous group social
      attention interactions modulates the relative weight assigned to others' gaze: we
      ignore the gaze of group followers.

PMID- 27031225
TI  - Thermal characterization of carbon nanotube foam using MEMS microhotplates and
      thermographic analysis.
AB  - Thermal material properties play a fundamental role in the thermal management of
      microelectronic systems. The porous nature of carbon nanotube (CNT) arrays
      results in a very high surface area to volume ratio, which makes the material
      attractive for surface driven heat transfer mechanisms. Here, we report on the
      heat transfer performance of lithographically defined micropins made of carbon
      nanotube (CNT) nanofoam, directly grown on microhotplates (MHPs). The MHP is used
      as an in situ characterization platform with controllable hot-spot and integrated
      temperature sensor. Under natural convection, and equivalent power supplied, we
      measured a significant reduction in hot-spot temperature when augmenting the MHP
      surface with CNT micropins. In particular, a strong enhancement of convective and
      radiative heat transfer towards the surrounding environment is recorded, due to
      the high aspect ratio and the foam-like morphology of the patterned CNTs. By
      combining electrical characterizations with high-resolution thermographic
      microscopy analysis, we quantified the heat losses induced by the integrated CNT
      nanofoams and we found a unique temperature dependency of the equivalent
      convective heat transfer coefficient, Hc. The obtained results with the proposed
      non-destructive characterization method demonstrate that significant improvements
      can be achieved in microelectronic thermal management and hierarchical structured
      porous material characterization. 

PMID- 27031226
TI  - Casp3/7-Instructed Intracellular Aggregation of Fe3O4 Nanoparticles Enhances T2
      MR Imaging of Tumor Apoptosis.
AB  - Large magnetic nanoparticles or aggregates are advantageous in their magnetic
      resonance properties over ultrasmall superparamagnetic iron oxide (USPIO)
      nanoparticles (NPs), but the former are cleared faster from the blood pool.
      Therefore, the "smart" strategy of intracellular aggregation of USPIO NPs is
      required for enhanced T2-weighted MR imaging. Herein, employing an enzyme
      instructed condensation reaction, we rationally designed a small molecule Ac-Asp
      Glu-Val-Asp-Cys(StBu)-Lys-CBT (1) to covalently modify USPIO NPs to prepare
      monodispersive Fe3O4@1 NPs. In vitro results showed that Fe3O4@1 NPs could be
      subjected to caspase 3 (Casp3)-instructed aggregation. T2 phantom MR imaging
      showed that the transverse molar relaxivity (r2) of Fe3O4@1 NPs with Casp3 or
      apoptotic HepG2 cells was significantly larger than those of control groups. In
      vivo tumor MR imaging results indicated that Fe3O4@1 NPs could be specifically
      applied for enhanced T2 MR imaging of tumor apoptosis. We propose that the enzyme
      instructed intracellular aggregation of Fe3O4 NPs could be a novel strategy for
      the design of "smart" probes for efficient T2 MR imaging of in vivo biomarkers. 

PMID- 27031228
TI  - LpMab-12 Established by CasMab Technology Specifically Detects Sialylated O
      Glycan on Thr52 of Platelet Aggregation-Stimulating Domain of Human Podoplanin.
AB  - Podoplanin (PDPN), also known as Aggrus, possesses three tandem repeat of
      platelet aggregation-stimulating (PLAG) domains in its N-terminus. Among the PLAG
      domains, sialylated O-glycan on Thr52 of PLAG3 is essential for the binding to C
      type lectin-like receptor-2 (CLEC-2) and the platelet-aggregating activity of
      human PDPN (hPDPN). Although various anti-hPDPN monoclonal antibodies (mAbs) have
      been generated, no specific mAb has been reported to target the epitope
      containing glycosylated Thr52. We recently established CasMab technology to
      develop mAbs against glycosylated membrane proteins. Herein, we report the
      development of a novel anti-glycopeptide mAb (GpMab), LpMab-12. LpMab-12 detected
      endogenous hPDPN by flow cytometry. Immunohistochemical analyses also showed that
      hPDPN-expressing lymphatic endothelial and cancer cells were clearly labeled by
      LpMab-12. The minimal epitope of LpMab-12 was identified as Asp49-Pro53 of hPDPN.
      Furthermore, LpMab-12 reacted with the synthetic glycopeptide of hPDPN,
      corresponding to 38-54 amino acids (hpp3854: 38-EGGVAMPGAEDDVVTPG-54), which
      carries alpha2-6 sialylated N-acetyl-D-galactosamine (GalNAc) on Thr52. LpMab-12
      did not recognize non-sialylated GalNAc-attached glycopeptide, indicating that
      sialylated GalNAc on Thr52 is necessary for the binding of LpMab-12 to hPDPN.
      Thus, LpMab-12 could serve as a new diagnostic tool for determining whether hPDPN
      possesses the sialylation on Thr52, a site-specific post-translational
      modification critical for the hPDPN association with CLEC-2. 

PMID- 27031227
TI  - Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement
      Revisited.
AB  - The biosynthetic pathway of peptidoglycan, an essential component of bacterial
      cell wall, is a well-recognized target for antibiotic development. Peptidoglycan
      precursors are synthesized in the bacterial cytosol by various enzymes including
      the ATP-hydrolyzing Mur ligases, which catalyze the stepwise addition of amino
      acids to a UDP-MurNAc precursor to yield UDP-MurNAc-pentapeptide. MurD catalyzes
      the addition of D-glutamic acid to UDP-MurNAc-L-Ala in the presence of ATP;
      structural and biochemical studies have suggested the binding of the substrates
      with an ordered kinetic mechanism in which ligand binding inevitably closes the
      active site. In this work, we challenge this assumption by reporting the crystal
      structures of intermediate forms of MurD either in the absence of ligands or in
      the presence of small molecules. A detailed analysis provides insight into the
      events that lead to the closure of MurD and reveals that minor structural
      modifications contribute to major overall conformation alterations. These novel
      insights will be instrumental in the development of new potential antibiotics
      designed to target the peptidoglycan biosynthetic pathway. 

PMID- 27031229
TI  - Healing by Secondary Intention.

PMID- 27031230
TI  - Analyzing the Long Term Cohesive Effect of Sector Specific Driving Forces.
AB  - Financial markets are partially composed of sectors dominated by external driving
      forces, such as commodity prices, infrastructure and other indices. We
      characterize the statistical properties of such sectors and present a novel model
      for the coupling of the stock prices and their dominating driving forces,
      inspired by mean reverting stochastic processes. Using the model we were able to
      explain the market sectors' long term behavior and estimate the coupling strength
      between stocks in financial markets and the sector specific driving forces.
      Notably, the analysis was successfully applied to the shipping market, in which
      the Baltic dry index (BDI), an assessment of the price of transporting the major
      raw materials by sea, influences the shipping financial market. We also present
      the analysis of other sectors-the gold mining market and the food production
      market, for which the model was also successfully applied. The model can serve as
      a general tool for characterizing the coupling between external forces and
      affected financial variables and therefore for estimating the risk in sectors and
      their vulnerability to external stress. 

PMID- 27031231
TI  - Artesunate-Amodiaquine and Artemether-Lumefantrine Therapies and Selection of
      Pfcrt and Pfmdr1 Alleles in Nanoro, Burkina Faso.
AB  - The adoption of Artemisinin based combination therapies (ACT) constitutes a basic
      strategy for malaria control in sub-Saharan Africa. Moreover, since cases of ACT
      resistance have been reported in South-East Asia, the need to understand P.
      falciparum resistance mechanism to ACT has become a global research goal. The
      selective pressure of ACT and the possibility that some specific Pfcrt and Pfmdr1
      alleles are associated with treatment failures was assessed in a clinical trial
      comparing ASAQ to AL in Nanoro. Dried blood spots collected on Day 0 and on the
      day of recurrent parasitaemia during the 28-day follow-up were analyzed using the
      restriction fragments length polymorphism (PCR-RFLP) method to detect single
      nucleotide polymorphisms (SNPs) in Pfcrt (codon76) and Pfmdr1 (codons 86, 184,
      1034, 1042, and 1246) genes. Multivariate analysis of the relationship between
      the presence of Pfcrt and Pfmdr1 alleles and treatment outcome was performed. AL
      and ASAQ exerted opposite trends in selecting Pfcrt K76T and Pfmdr1-N86Y alleles,
      raising the potential beneficial effect of using diverse ACT at the same time as
      first line treatments to reduce the selective pressure by each treatment regimen.
      No clear association between the presence of Pfcrt and Pfmdr1 alleles carried at
      baseline and treatment failure was observed. 

PMID- 27031232
TI  - Analytic Approximate Solutions to the Boundary Layer Flow Equation over a
      Stretching Wall with Partial Slip at the Boundary.
AB  - Analytic approximate solutions using Optimal Homotopy Perturbation Method (OHPM)
      are given for steady boundary layer flow over a nonlinearly stretching wall in
      presence of partial slip at the boundary. The governing equations are reduced to
      nonlinear ordinary differential equation by means of similarity transformations.
      Some examples are considered and the effects of different parameters are shown.
      OHPM is a very efficient procedure, ensuring a very rapid convergence of the
      solutions after only two iterations. 

PMID- 27031234
TI  - Comparing the Information and Support Needs of Different Population Groups in
      Preparation for 2015 Government Approval for HIV Self-testing in France.
AB  - CONTEXT: HIV self-tests are currently being introduced in France with the aim of
      promoting screening both for the general population and for high-risk
      populations. OBJECTIVE: The current study aimed to identify and compare the
      information and support needs of the different target population groups. METHODS:
      The Delphi process was used to synthesize expert opinions for each population
      group. Experts were chosen for their experience and expertise in the area of HIV
      and HIV screening for each population. Each group developed recommendations for a
      specific population: six high HIV prevalence populations (men who have sex with
      men; transgender people; substance users; migrants from sub-Saharan Africa;
      French West Indies; French Guiana) and two low prevalence populations (the
      general population; people under 25). Each group included expertise from four
      areas: research, screening and care, policy-making, and community groups.
      RESULTS: A final total of 263 recommendations were grouped into eight main
      themes: Communicating at both national and community levels about self-test
      arrival (24% of all recommendations); Providing information adapted to the
      different community groups' needs (23%); Providing counselling on self-test use
      and access to care (15%); Making self-tests available to all in terms of
      accessibility and cost (13%); Preparing community healthcare and screening
      systems for the arrival of the self-test (11%); Approving only high quality self
      tests (6%); Defending self-test users' legal rights (5%); Evaluating self-test
      use (3%). Although a large number of recommendations were common to several
      groups of experts, the study highlighted a certain number of recommendations
      specific to each different population group, particularly with regard to
      information content and access both to information and to the self-tests
      themselves. CONCLUSION: Results from the current study should make a significant
      contribution to policy decisions concerning catering for the specific access,
      information and support needs of different potential HIV self-test user groups in
      France.

PMID- 27031233
TI  - Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates
      Establishment of Cell Lines with Reduced mtDNA Copy Number.
AB  - Due to the essential role played by mitochondrial DNA (mtDNA) in cellular
      physiology and bioenergetics, methods for establishing cell lines with altered
      mtDNA content are of considerable interest. Here, we report evidence for the
      existence in mammalian cells of a novel, low- efficiency, presequence-independent
      pathway for mitochondrial protein import, which facilitates mitochondrial uptake
      of such proteins as Chlorella virus ligase (ChVlig) and Escherichia coli LigA.
      Mouse cells engineered to depend on this pathway for mitochondrial import of the
      LigA protein for mtDNA maintenance had severely (up to >90%) reduced mtDNA
      content. These observations were used to establish a method for the generation of
      mouse cell lines with reduced mtDNA copy number by, first, transducing them with
      a retrovirus encoding LigA, and then inactivating in these transductants
      endogenous Lig3 with CRISPR-Cas9. Interestingly, mtDNA depletion to an average
      level of one copy per cell proceeds faster in cells engineered to maintain mtDNA
      at low copy number. This makes a low-mtDNA copy number phenotype resulting from
      dependence on mitochondrial import of DNA ligase through presequence-independent
      pathway potentially useful for rapidly shifting mtDNA heteroplasmy through
      partial mtDNA depletion. 

PMID- 27031235
TI  - Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis
      Involving Twelve Case-Control Studies.
AB  - Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor
      responses, so it is considered as a powerful candidate gene for individual's
      genetic susceptibility to cancer. Recently, some epidemiological studies have
      evaluated the association between PD-1 polymorphisms and cancer risk. However,
      the results of the studies are conflicting. Therefore, a meta-analysis was
      performed. We identified all studies reporting the relationship between PD-1
      polymorphisms and cancers by electronically searches. According to the inclusion
      criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high
      quality studies were included. A total of twelve relevant studies involving 5,206
      cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism,
      significantly decreased cancer risks were obtained among overall population,
      Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC
      genetic models. In addition, a similar result was also found in T vs. C allele
      for overall population. However, there were no significant associations between
      either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all
      genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found
      different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic
      models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A
      vs. G allele and cancer risks. In general, our results firstly indicated that PD
      1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers.
      Additional epidemiological studies are needed to confirm our findings. 

PMID- 27031236
TI  - Comparison of Clinicopathological Features and Treatments between Young (<=40
      Years) and Older (>40 Years) Female Breast Cancer Patients in West China: A
      Retrospective, Epidemiological, Multicenter, Case Only Study.
AB  - The incidence of young cases of breast cancer is higher in China compared to the
      western world. We aimed to explore differences in risk factors,
      clinicopathological features and treatment modes of young female breast cancer
      compared to older patients in West China. We collected clinical information from
      12,209 female breast cancer patients in West China, including risk factors,
      clinicopathological features and treatment modes, from January 2010 to December
      2012. Chi-square tests and the multivariate logistic regression analysis were
      applied for statistical analysis. There were 2,682 young (<=40 years) cases and
      9,527 older cases at the time of breast cancer diagnosis. Young patients had a
      greater tumor diameter at diagnosis, and a higher probability of axillary lymph
      node and distant metastasis (P < 0.05). The progesterone receptor positive
      expression rate, estrogen receptor/progesterone receptor double positive
      expression rate, and human epidermal growth factor receptor 2 (HER2) negative
      expression rate was higher in young patients compared to older patients (P <
      0.05). For young patients, the age at menarche was earlier, they had lower
      marriage rates, fewer pregnancies and births, and a lower breastfeeding rate (P <
      0.05). A higher proportion of young patients underwent advanced operations,
      neoadjuvant and adjuvant chemotherapy, radiotherapy, and endocrine therapy
      compared to older patients (P < 0.05). We found significant differences in the
      clinicopathological features, risk factors and treatment modes between young
      (<=40 years) and older (>40 years) female breast cancer patients in West China.
      As some of these results differ from those found in the western female
      population, it is likely that the mechanism of tumorigenesis of young female
      breast cancer patients in West China may differ from that in western developed
      countries. Further investigation into the regional differences in breast cancer
      tumorigenesis is warranted. 

PMID- 27031237
TI  - Further Evidence That Cataract Surgery Is Not Associated With Macular
      Degeneration Progression.

PMID- 27031238
TI  - Deltamethrin-Mediated Toxicity and Cytomorphological Changes in the Midgut and
      Nervous System of the Mayfly Callibaetis radiatus.
AB  - Immature instars of mayflies are important constituents of the food web in
      aquatic ecosystems (especially in Neotropical regions) and they are among the
      most susceptible arthropods to pyrethroid insecticides. These insecticides have
      been recognized as important stressors of freshwater ecosystems, but their
      cellular effects in aquatic insects have been neglected. Here, we assessed the
      susceptibility to deltamethrin (a typical type II pyrethroid) as well as the
      deltamethrin-mediated cytomorphological changes in the central nervous system and
      midgut of the mayfly Callibaetis radiatus. While the deltamethrin LC50 for 24 h
      of exposure was of 0.60 (0.46-0.78) MUg of a.i/L, the survival of C. radiatus was
      significantly reduced in deltamethrin concentrations >= 0.25 MUg a.i/L at 96 h of
      exposure. Sub-lethal deltamethrin exposure severely affected the cytomorphology
      of C. radiatus midgut (e.g., muscle layer retraction, cytoplasm vacuolation,
      nucleus and striated border disorganization) and also induced slight
      cytomorphological changes in the brain (e.g., presence of pyknotic nuclei) and in
      the thoracic ganglia (e.g., vacuolation of neurons and presence of pyknotic
      nuclei) of these insects. However, DNA damage was absent in all of these organs,
      suggesting that the sublethal cellular stress induced by deltamethrin might
      disrupt physiological processes (e.g., metabolism or electrical signal
      transmission) rather than cause cell death (e.g., apoptosis) in C. radiatus.
      Thus, our findings indicated that deltamethrin actions at cellular levels
      represent a clear indication of sublethal effects on the C. radiatus survival
      abilities.

PMID- 27031239
TI  - Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host
      Disease of the Intestine by Expansion of Regulatory T Cells.
AB  - Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological
      phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host
      disease (GVHD), we previously reported that it was highly efficacious for
      cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg)
      cells induced by NB-UVB might be one of the mechanisms. In order to examine
      whether NB-UVB irradiation through expansion of Treg cells is effective for the
      treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the
      intestine or liver, we conducted experiments in which a murine lethal aGVHD
      model, characterized by severe involvement of the intestine, was irradiated with
      NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival
      rate. The pathological score of aGVHD was improved in all affected organs:
      intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the
      levels of Treg cells-associated cytokines such as transforming growth factor beta
      (TGFbeta) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating
      Treg cells in inflamed tissue of the intestine and those in spleen were increased
      in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB
      phototherapy has the ability to ameliorate intestinal aGVHD through the expansion
      of Treg cells. 

PMID- 27031240
TI  - Evolution of Social Insect Polyphenism Facilitated by the Sex Differentiation
      Cascade.
AB  - The major transition to eusociality required the evolution of a switch to
      canalize development into either a reproductive or a helper, the nature of which
      is currently unknown. Following predictions from the 'theory of facilitated
      variation', we identify sex differentiation pathways as promising candidates
      because of their pre-adaptation to regulating development of complex phenotypes.
      We show that conserved core genes, including the juvenile hormone-sensitive
      master sex differentiation gene doublesex (dsx) and a kruppel homolog 2 (kr-h2)
      with putative regulatory function, exhibit both sex and morph-specific expression
      across life stages in the ant Cardiocondyla obscurior. We hypothesize that genes
      in the sex differentiation cascade evolved perception of alternative input
      signals for caste differentiation (i.e. environmental or genetic cues), and that
      their inherent switch-like and epistatic behavior facilitated signal transfer to
      downstream targets, thus allowing them to control differential development into
      morphological castes. 

PMID- 27031241
TI  - Prevalence of Cryptosporidium spp., Enterocytozoon bieneusi, Encephalitozoon spp.
      and Giardia intestinalis in Wild, Semi-Wild and Captive Orangutans (Pongo abelii
      and Pongo pygmaeus) on Sumatra and Borneo, Indonesia.
AB  - BACKGROUND: Orangutans are critically endangered primarily due to loss and
      fragmentation of their natural habitat. This could bring them into closer contact
      with humans and increase the risk of zoonotic pathogen transmission. AIMS: To
      describe the prevalence and diversity of Cryptosporidium spp., microsporidia and
      Giardia intestinalis in orangutans at seven sites on Sumatra and Kalimantan, and
      to evaluate the impact of orangutans' habituation and location on the occurrence
      of these zoonotic protists. RESULT: The overall prevalence of parasites in 298
      examined animals was 11.1%. The most prevalent microsporidia was Encephalitozoon
      cuniculi genotype II, found in 21 animals (7.0%). Enterocytozoon bieneusi
      genotype D (n = 5) and novel genotype Pongo 2 were detected only in six
      individuals (2.0%). To the best of our knowledge, this is the first report of
      these parasites in orangutans. Eight animals were positive for Cryptosporidium
      spp. (2.7%), including C. parvum (n = 2) and C. muris (n = 6). Giardia
      intestinalis assemblage B, subtype MB6, was identified in a single individual.
      While no significant differences between the different human contact level groups
      (p = 0.479-0.670) or between the different islands (p = 0.992) were reported in
      case of E. bieneusi or E. cuniculi, Cryptosporidium spp. was significantly less
      frequently detected in wild individuals (p < 2*10-16) and was significantly more
      prevalent in orangutans on Kalimantan than on Sumatra (p < 2*10-16). CONCLUSION:
      Our results revealed that wild orangutans are significantly less frequently
      infected by Cryptosporidium spp. than captive and semi-wild animals. In addition,
      this parasite was more frequently detected at localities on Kalimantan. In
      contrast, we did not detect any significant difference in the prevalence of
      microsporidia between the studied groups of animals. The sources and transmission
      modes of infections were not determined, as this would require repeated sampling
      of individuals, examination of water sources, and sampling of humans and animals
      sharing the habitat with orangutans.

PMID- 27031242
TI  - Synchronous Bioimaging of Intracellular pH and Chloride Based on LSS Fluorescent
      Protein.
AB  - Ion homeostasis regulates critical physiological processes in the living cell.
      Intracellular chloride concentration not only contributes in setting the membrane
      potential of quiescent cells but it also plays a role in modulating the dynamic
      voltage changes during network activity. Dynamic chloride imaging demands new
      tools, allowing faster acquisition rates and correct accounting of concomitant pH
      changes. Joining a long-Stokes-shift red-fluorescent protein to a GFP variant
      with high sensitivity to pH and chloride, we obtained LSSmClopHensor, a
      genetically encoded fluorescent biosensor optimized for the simultaneous chloride
      and pH imaging and requiring only two excitation wavelengths (458 and 488 nm).
      LSSmClopHensor allowed us to monitor the dynamic changes of intracellular pH and
      chloride concentration during seizure like discharges in neocortical brain
      slices. Only cells with tightly controlled resting potential revealed a narrow
      distribution of chloride concentration peaking at about 5 and 8 mM, in
      neocortical neurons and SK-N-SH cells, respectively. We thus showed that
      LSSmClopHensor represents a new versatile tool for studying the dynamics of
      chloride and proton concentration in living systems.

PMID- 27031244
TI  - Correction to "Anisotropic Growth of TiO2 onto Gold Nanorods for Plasmon-Enhanced
      Hydrogen Production from Water Reduction".

PMID- 27031243
TI  - Predicting Missing Marker Trajectories in Human Motion Data Using Marker
      Intercorrelations.
AB  - Missing information in motion capture data caused by occlusion or detachment of
      markers is a common problem that is difficult to avoid entirely. The aim of this
      study was to develop and test an algorithm for reconstruction of corrupted marker
      trajectories in datasets representing human gait. The reconstruction was
      facilitated using information of marker inter-correlations obtained from a
      principal component analysis, combined with a novel weighting procedure. The
      method was completely data-driven, and did not require any training data. We
      tested the algorithm on datasets with movement patterns that can be considered
      both well suited (healthy subject walking on a treadmill) and less suited
      (transitioning from walking to running and the gait of a subject with cerebral
      palsy) to reconstruct. Specifically, we created 50 copies of each dataset, and
      corrupted them with gaps in multiple markers at random temporal and spatial
      positions. Reconstruction errors, quantified by the average Euclidian distance
      between predicted and measured marker positions, was <= 3 mm for the well suited
      dataset, even when there were gaps in up to 70% of all time frames. For the less
      suited datasets, median reconstruction errors were in the range 5-6 mm. However,
      a few reconstructions had substantially larger errors (up to 29 mm). Our results
      suggest that the proposed algorithm is a viable alternative both to conventional
      gap-filling algorithms and state-of-the-art reconstruction algorithms developed
      for motion capture systems. The strengths of the proposed algorithm are that it
      can fill gaps anywhere in the dataset, and that the gaps can be considerably
      longer than when using conventional interpolation techniques. Limitations are
      that it does not enforce musculoskeletal constraints, and that the reconstruction
      accuracy declines if applied to datasets with less predictable movement patterns.

PMID- 27031245
TI  - Correction: Host Factors and Biomarkers Associated with Poor Outcomes in Adults
      with Invasive Pneumococcal Disease.

PMID- 27031246
TI  - The E3 Ligase APIP10 Connects the Effector AvrPiz-t to the NLR Receptor Piz-t in
      Rice.
AB  - Although nucleotide-binding domain, leucine-rich repeat (NLR) proteins are the
      major immune receptors in plants, the mechanism that controls their activation
      and immune signaling remains elusive. Here, we report that the avirulence
      effector AvrPiz-t from Magnaporthe oryzae targets the rice E3 ligase APIP10 for
      degradation, but that APIP10, in return, ubiquitinates AvrPiz-t and thereby
      causes its degradation. Silencing of APIP10 in the non-Piz-t background
      compromises the basal defense against M. oryzae. Conversely, silencing of APIP10
      in the Piz-t background causes cell death, significant accumulation of Piz-t, and
      enhanced resistance to M. oryzae, suggesting that APIP10 is a negative regulator
      of Piz-t. We show that APIP10 promotes degradation of Piz-t via the 26S
      proteasome system. Furthermore, we demonstrate that AvrPiz-t stabilizes Piz-t
      during M. oryzae infection. Together, our results show that APIP10 is a novel E3
      ligase that functionally connects the fungal effector AvrPiz-t to its NLR
      receptor Piz-t in rice. 

PMID- 27031248
TI  - Characterizing the Effect of Salt and Surfactant Concentration on the Counterion
      Atmosphere around Surfactant Stabilized SWCNTs Using Analytical
      Ultracentrifugation.
AB  - Accurate characterization of dispersed-phase nanoparticle properties such as
      density, size, solvation, and charge is necessary for their utilization in
      applications such as medicine, energy, and materials. Herein, analytical
      ultracentrifugation (AUC) is used to quantify bile salt surfactant adsorption on
      length sorted (7,6) single-wall carbon nanotubes (SWCNTs) as a function of bulk
      surfactant concentration and in the presence of varying quantities of a
      monovalent salt-sodium chloride. These measurements provide high precision
      adsorbed surfactant density values in the literature for only the second SWCNT
      structure to date and report the quantity of adsorbed surfactant across a broad
      range of bulk surfactant concentrations utilized in SWCNT dispersion processing.
      Second, the measurements presented herein unambiguously demonstrate, via AUC, a
      direct relation between the size of the counterion cloud around a surfactant
      stabilized SWCNT and solution ionic strength. The results show that changes in
      the size of the counterion cloud around surfactant-stabilized SWCNT are
      attributable to electrostatic phenomenon and not to changes in the quantity of
      adsorbed surfactant with salt addition. These results provide important reference
      values for projecting SWCNT dispersion behavior as a function of solution
      conditions and extend the range of nanoparticle properties measurable via AUC.

PMID- 27031247
TI  - AZD2014 Radiosensitizes Oral Squamous Cell Carcinoma by Inhibiting AKT/mTOR Axis
      and Inducing G1/G2/M Cell Cycle Arrest.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common
      malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been
      linked to decreased radiation responsiveness in human oral cancer, thus it limits
      efficacy of radiotherapy. To address this question, we investigated the effect of
      AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2
      kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models.
      METHODS: We isolated primary tumor cells from OSCC tissues and cell lines.
      AZD2014 was administered with and without ionizing radiation. The
      radiosensitizing effect of AZD2014 were then assessed using cell viability
      assays, clonogenic survival assays, and cell cycle analyses. Western blotting was
      used to detect protein expression. RESULTS: Combination treatment with AZD2014
      and irradiation resulted in significant reduction in OSCC cell line and primary
      OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1
      and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells
      induced tumor cell cycle arrest at the G1 and G2/M phases, which led to
      disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014
      synergized with radiation to promote both apoptosis and autophagy by increasing
      caspase-3 and LC3 in primary OSCC cells. CONCLUSIONS: These findings suggest that
      in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and
      mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell
      carcinoma.

PMID- 27031249
TI  - Whole-Genome Sequencing and Comparative Analysis of Mycobacterium brisbanense
      Reveals a Possible Soil Origin and Capability in Fertiliser Synthesis.
AB  - Mycobacterium brisbanense is a member of Mycobacterium fortuitum third biovariant
      complex, which includes rapidly growing Mycobacterium spp. that normally inhabit
      soil, dust and water, and can sometimes cause respiratory tract infections in
      humans. We present the first whole-genome analysis of M. brisbanense UM_WWY which
      was isolated from a 70-year-old Malaysian patient. Molecular phylogenetic
      analyses confirmed the identification of this strain as M. brisbanense and showed
      that it has an unusually large genome compared with related mycobacteria. The
      large genome size of M. brisbanense UM_WWY (~7.7Mbp) is consistent with further
      findings that this strain has a highly variable genome structure that contains
      many putative horizontally transferred genomic islands and prophage. Comparative
      analysis showed that M. brisbanense UM_WWY is the only Mycobacterium species that
      possesses a complete set of genes encoding enzymes involved in the urea cycle,
      suggesting that this soil bacterium is able to synthesize urea for use as plant
      fertilizers. It is likely that M. brisbanense UM_WWY is adapted to live in soil
      as its primary habitat since the genome contains many genes associated with
      nitrogen metabolism. Nevertheless, a large number of predicted virulence genes
      were identified in M. brisbanense UM_WWY that are mostly shared with well-studied
      mycobacterial pathogens such as Mycobacterium tuberculosis and Mycobacterium
      abscessus. These findings are consistent with the role of M. brisbanense as an
      opportunistic pathogen of humans. The whole-genome study of UM_WWY has provided
      the basis for future work of M. brisbanense. 

PMID- 27031253
TI  - Treatment Modification in Young Breast Cancer Patients.
AB  - Patients not older than 40 years are referred to as young patients. These women
      benefit from chemo-, endocrine and anti-HER2 therapy to a similar degree as older
      women. Surgery and radiation therapy also follow the same recommendations. This
      manuscript deals with the following topics that need special consideration in
      young women: endocrine therapy and ovarian suppression; fertility protection and
      family planning; and genetic counselling. There is an on-going debate on whether
      tamoxifen is sufficient as an endocrine treatment in young patients with
      endocrine-responsive tumours or whether suppression of ovarian function in
      combination with tamoxifen or aromatase inhibitor should be preferred. Recent
      data suggest a benefit from ovarian suppression plus exemestane in women of 35
      years or younger with high-risk breast cancer. However, increased side effects
      bear the risk of lesser compliance, which eventually results in higher mortality.
      Child bearing is nowadays frequently postponed to the 4th decade of life, thereby
      increasing the number of women who have not yet finished their reproductive
      desires when diagnosed with breast cancer. These patients are in urgent need of
      counselling for fertility protection. Breast cancer diagnosis at young age is an
      indication for a possible mutation in breast cancer susceptibility genes. This
      has an impact on the cancer risk of the whole family, especially the offspring.
      Drugs that are specifically targeted to cancer cells with genetic alterations
      that impair DNA repair are already entering the arsenal of oncologists. 

PMID- 27031254
TI  - Synthesis of Capsule-like Porous Hollow Nanonickel Cobalt Sulfides via Cation
      Exchange Based on the Kirkendall Effect for High-Performance Supercapacitors.
AB  - To construct a suitable three-dimensional structure for ionic transport on the
      surface of the active materials for a supercapacitor, porous hollow nickel cobalt
      sulfides are successfully synthesized via a facile and efficient cation-exchange
      reaction in a hydrothermal process involving the Kirkendall effect with gamma-MnS
      nanorods as a sacrificial template. The formation mechanism of the hollow nickel
      cobalt sulfides is carefully illustrated via the tuning reaction time and
      reaction temperature during the cation-exchange process. Due to the ingenious
      porous hollow structure that offers a high surface area for electrochemical
      reaction and suitable paths for ionic transport, porous hollow nickel cobalt
      sulfide electrodes exhibit high electrochemical performance. The
      Ni(1.77)Co(1.23)S4 electrode delivers a high specific capacity of 224.5 mAh g(-1)
      at a current density of 0.25 A g(-1) and a high capacity retention of 87.0% at 10
      A g(-1). An all-solid-state asymmetric supercapacitor, assembled with a
      Ni(1.77)Co(1.23)S4 electrode as the positive electrode and a homemade activated
      carbon electrode as the negative electrode (denoted as NCS//HMC), exhibits a high
      energy density of 42.7 Wh kg(-1) at a power density of 190.8 W kg(-1) and even
      29.4 Wh kg(-1) at 3.6 kW kg(-1). The fully charged as-prepared asymmetric
      supercapacitor can light up a light emitting diode (LED) indicator for more than
      1 h, indicating promising practical applications of the hollow nickel cobalt
      sulfides and the NCS//HMC asymmetric supercapacitor.

PMID- 27031255
TI  - Cost per median overall survival month associated with abiraterone acetate and
      enzalutamide for treatment of patients with metastatic castration-resistant
      prostate cancer.
AB  - OBJECTIVE: To calculate costs per median overall survival (OS) month in
      chemotherapy-naive patients with metastatic castration-resistant prostate cancer
      (mCRPC) treated with abiraterone acetate plus prednisone (AA + P) or
      enzalutamide. METHODS: Median treatment duration and median OS data from
      published Phase 3 clinical trials and prescribing information were used to
      calculate costs per median OS month based on wholesale acquisition costs (WACs)
      for patients with mCRPC treated with AA + P or enzalutamide. Sensitivity analyses
      were performed to understand how variations in treatment duration and treatment
      related monitoring recommendations influenced cost per median OS month. Cost
      effectiveness estimates of other Phase 3 trial outcomes were also explored: cost
      per month of chemotherapy avoided and per median radiographic progression-free
      survival (rPFS) month. RESULTS: The results demonstrated that AA + P has a lower
      cost per median OS month than enzalutamide ($3231 vs 4512; 28% reduction), based
      on the following assumptions: median treatment duration of 14 months for AA + P
      and 18 months for enzalutamide, median OS of 34.7 months for AA + P and 35.3
      months for enzalutamide, and WAC per 30-day supply of $8007.17 for AA + P vs
      $8847.98 for enzalutamide. Sensitivity analyses showed that accounting for
      recommended treatment-related monitoring costs or assuming identical treatment
      durations for AA + P and enzalutamide (18 months) resulted in costs per median OS
      month 8-27% lower for AA + P than for enzalutamide. Costs per month of
      chemotherapy avoided were $4448 for AA + P and $5688 for enzalutamide, while
      costs per month to achieve median rPFS were $6794 for AA + P and $7963 for
      enzalutamide. CONCLUSIONS: This cost-effectiveness analysis demonstrated that
      costs per median OS month, along with costs of other Phase 3 trial outcomes, were
      lower for AA + P than for enzalutamide. The findings were robust to sensitivity
      analyses. These results have important implications for population health
      decision-makers evaluating the relative value of therapies for mCRPC patients.

PMID- 27031256
TI  - Lamivudine Monotherapy: Experience of Medium-term Outcomes in HIV-infected
      Children Unable to Adhere to Triple Therapy.
AB  - BACKGROUND: HIV-infected children in resource-poor settings who fail or default
      from first-line antiretroviral therapy have limited alternative options. By
      preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is
      occasionally used while awaiting patient readiness for second- or third-line
      therapy, but this strategy has not been widely studied. METHODS: A retrospective
      review of all eligible LM events (>=3 months) from a cohort of two linked health
      facilities in the Eastern Cape Province, South Africa was undertaken. Events were
      disaggregated according to absolute CD4 count at initiation (Group 1:
      >200cells/MUl, n=64; Group 2: <=200cells/MUl, n=7). Study endpoints were defined
      as a decline of absolute CD4 by >=25% or to <=200 cells/MUl or World Health
      Organization stage 3 or 4 event (immunologic outcomes) or (re)initiation of
      second- or third-line therapy (real-world outcomes). RESULTS: Eligible LM events
      were identified among 71 children (56.4% male; median age at LM initiation 9.6
      years). 71.8% (n = 51) had a drop in CD4 count of >=25%, 15.6% (n = 10) of those
      whose CD4 counts had been >200 cells/MUl dropped to <=200 cells/MUl and 8.1% (n =
      6) experienced a stage 3 or 4 event; CD4 decreases and stage 3 or 4 events did
      not differ significantly between groups. No deaths were recorded. Children
      commencing LM with CD4 counts <=200cells/MUl had a shorter mean "real-world"
      duration of LM before switching to second/third line therapy (11.38 months vs.
      26.1 months, P < 0.0001) and experienced immunologic outcomes at an earlier stage
      (5.29 vs. 9.2 months, P = 0.023). CONCLUSIONS: LM offers a potential alternative
      approach to antiretroviral therapy management in young patients pending
      availability and/or willingness to adhere to second- or third-line therapies but
      is associated with substantial immunologic decline. This strategy should be
      avoided in patients with CD4 <=200 cells/MUl.

PMID- 27031257
TI  - The History and Current Relevance of the Eponymous Signs of Meningitis.
AB  - During the past several decades, researchers have shown that the eponymous signs
      of meningitis have reduced sensitivity and specificity compared with when they
      were originally described. This may be because of the changing epidemiology of
      meningitis and its treatment or it may be because of variations in performance of
      the maneuvers. For example, in the original descriptions, the Kernig sign
      (resistance of leg extension) is best elicited with the patient sitting and the
      Brudzinski nape of the neck sign involves holding down the patient's chest as the
      neck is flexed. These and other lesser-known signs of meningitis by Amoss,
      Bikeles and Edelmann all relate to the mechanics of stretching inflamed meninges,
      and this review will allow the clinician to understand how the history related to
      these maneuvers is still germane to clinical practice today.

PMID- 27031258
TI  - TRACnet Internet and Short Message Service Technology Improves Time to
      Antiretroviral Therapy Initiation Among HIV-infected Infants in Rwanda.
AB  - BACKGROUND: Delays in testing HIV-exposed infants and obtaining results in
      resource-limited settings contribute to delays for initiating antiretroviral
      therapy (ART) in infants. To overcome this challenge, Rwanda expanded its
      national mobile and Internet-based HIV/AIDS informatics system, called TRACnet,
      to include HIV polymerase chain reaction (PCR) results in 2010. This study was
      performed to evaluate the impact of TRACnet technology on the time to delivery of
      test results and the subsequent initiation of ART in HIV-infected infants.
      METHODS: A retrospective cohort study was conducted on 380 infants who initiated
      ART in 190 health facilities in Rwanda from March 2010 to June 2013. Program data
      collected by the TRACnet system were extracted and analyzed. RESULTS: Since the
      introduction of TRACnet for processing PCR results, the time to receive results
      has significantly decreased from a median of 144 days [interquartile range (IQR):
      121-197 days] to 23 days (IQR: 17-43 days). The number of days between PCR
      sampling and health facility receipt of results decreased substantially from a
      median of 90 days (IQR: 83-158 days) to 5 days (IQR: 2-8 days). After receiving
      PCR results at a health facility, it takes a median of 44 days (IQR: 32-77 days)
      before ART initiation. Result turnaround time was significantly associated with
      time to initiating ART (P < 0.001). An increased number of staff trained for HIV
      care and treatment was also significantly associated with decreased time to ART
      initiation (P = 0.004). CONCLUSIONS: The use of mobile technology for
      communication of HIV PCR results, coupled with well-trained and skilled
      personnel, can reduce delays in communicating results to providers. Such
      reductions may improve timely ART initiation in resource-limited settings.

PMID- 27031259
TI  - Etiology, Antibiotic Resistance and Risk Factors for Neonatal Sepsis in a Large
      Referral Center in Zambia.
AB  - BACKGROUND: In sub-Saharan Africa, there is scanty data on the causes of neonatal
      sepsis and antimicrobial resistance among common invasive pathogens that might
      guide policy and practice. METHODS: A cross-sectional observational prevalence
      and etiology study of neonates with suspected sepsis admitted to the neonatal
      intensive care unit, University Teaching Hospital, Lusaka, Zambia, between
      October 2013 and May 2014. Data from blood cultures and phenotypic antibiotic
      susceptibility testing were compared with multivariate analysis of risk factors
      for neonatal sepsis. RESULTS: Of 313 neonates with suspected sepsis, 54%
      (170/313) were male; 20% (62/313) were born to HIV-positive mothers; 33%
      (103/313) had positive blood cultures, of which 85% (88/103) were early-onset
      sepsis. Klebsiella species was the most prevalent isolate, accounting for 75%
      (77/103) of cases, followed by coagulase-negative staphylococci [6% (7/103)],
      Staphylococcus aureus [6% (6/103)], Escherichia coli [5% (5/103)] and Candida
      species [5% (5/103)]. For Klebsiella species, antibiotic resistance ranged from
      96%-99% for World Health Organization-recommended first-line therapy (gentamicin
      and ampicillin/penicillin) to 94%-97% for third-generation cephalosporins. The
      prevalence of culture-confirmed sepsis increased from 0 to 39% during the period
      December 2013 to March 2014, during which time mortality increased 29%-47%; 93%
      (14/15) of late-onset sepsis and 82% (37/45) of early-onset sepsis aged 4-7 days
      were admitted >2 days before the onset of symptoms. Culture results for only 25%
      (26/103) of cases were available before discharge or death. Maternal HIV
      infection was associated with a reduced risk of neonatal sepsis [odds ratio, 0.46
      (0.23-0.93); P = 0.029]. CONCLUSIONS: Outbreaks of nosocomial multiantibiotic
      resistant infections are an important cause of neonatal sepsis and associated
      mortality. Reduced risk of neonatal sepsis associated with maternal HIV infection
      is counterintuitive and requires further investigation.

PMID- 27031260
TI  - Jiulongibacter sediminis gen. nov., sp. nov., a new member of the family
      Cytophagaceae, isolated from the surface sediment of the Jiulong River in China.
AB  - A bacterial strain, designated JN14-9T, was isolated from surface sediment of the
      Jiulong River and characterized in a taxonomic study using a polyphasic approach.
      Strain JN14-9T was Gram-stain-negative, non-motile, rod-shaped and orange
      pigmented. It can grow at 15-37  degrees C (optimum 25-30  degrees C), at pH 7-8
      (optimum pH 7) and in 2-6 % (w/v) NaCl (optimum 3-4 %). Phylogenetic analyses
      based on 16S rRNA gene sequences showed that strain JN14-9T formed an independent
      lineage related to the family Cytophagaceae with low 16S rRNA gene sequence
      similarities (<92.5 %) to members of other genera with validly published names.
      The principal fatty acids of strain JN14-9T were summed feature 3
      (C16:1omega6c/C16:1omega7c) and iso-C15:0. The isoprenoid quinone was identified
      as MK-7. The major polar lipids comprised diphosphatidylglycerol,
      phosphatidylethanolamine, three aminophospholipids and five unidentified
      phospholipids. The DNA G+C content was 41.6 mol%. Results of phenotypic,
      phylogenetic and chemotaxonomic analyses clearly indicate that strain JN14-9T
      represents a novel species of a new genus within the family Cytophagaceae, for
      which the name Jiulongibacter sediminis gen. nov., sp. nov. is proposed. The type
      strain of the type species is JN14-9T (=MCCC 1A00733T=KCTC 42153T). 

PMID- 27031261
TI  - Oceanivirga salmonicida gen. nov., sp. nov., a member of the Leptotrichiaceae
      isolated from Atlantic salmon (Salmo salar).
AB  - A pleomorphic, Gram-negative, rod-shaped, indole-, oxidase- and catalase-
      negative, non-spore-forming, non-motile bacterium was originally isolated in 1992
      from moribund, seawater farmed Atlantic salmon with multifocal tissue necrosis.
      Strain AVG 2115T displayed considerable similarities with Streptobacillus
      moniliformis, one of the two etiological agents of rat bite fever, and has been
      stored as Streptobacillus sp. NCIMB 703044T. On the basis of 16S rRNA gene
      sequence analyses, this strain displayed >99 % sequence similarities with
      uncultured bacterial clones from the digestive tracts of marine mammals, followed
      by Sneathia sanguinegens CCUG 41628T (92.7 %), 'Sneathia amnii' Sn35 (92.5 %),
      Caviibacter abscessus CCUG 39713T (92.2 %), Streptobacillus ratti OGS16T (91.3
      %), Streptobacillus notomytis AHL 370-1T (91.2 %), S. moniliformis DSM 12112T
      (91.0 %), Streptobacillus felis 131000547T (90.9 %) and Streptobacillus
      hongkongensis DSM 26322T (89.7 %). Sequence similarities to all other taxa were
      below 89 %. Phylogenetic analysis for strain NCIMB 703044T revealed highly
      similar results for gyrB, groEL and recA nucleotide and deduced amino acid
      sequence analyses independent of the employed treeing method. Average nucleotide
      identities (ANI) for complete genomes ranged from 66.00 % to 72.08 % between
      strain NCIMB 703044T and the type strains of Sebaldella termitidis,
      Leptotrichiabuccalis, Streptobacillus moniliformis, Sneathia sanguinegens and
      Caviibacter abscessus. Chemotaxonomic and physiological data of strain NCIMB
      703044t were in congruence with closely related members of the family
      Leptotrichiaceae, represented by highly similar enzyme profiles and fatty acid
      patterns. MALDI-TOF MS analysis was capable to clearly discriminate strain NCIMB
      703044T from all currently described taxa of the family Leptotrichiaceae. On the
      basis of these data we propose the novel taxon Oceanivirga salmonicida gen. nov.
      sp. nov. with the type strain AVG 2115T (=NCIMB 703044T) (=DSM 101867T). The G+C
      content is 25.4 %, genome size is 1.77 Mbp. 

PMID- 27031262
TI  - Mitochondrial outer membrane forms bridge between two mitochondria in Arabidopsis
      thaliana.
AB  - Mitochondria are double-membrane organelles that move around and change their
      shapes dynamically. In plants, the dynamics of the outer membrane is not well
      understood. We recently demonstrated that mitochondria had tubular protrusions of
      the outer membrane with little or no matrix, called MOPs (mitochondrial outer
      membrane protrusions; MOPs). Here we show that a MOP can form a bridge between
      two mitochondria in Arabidopsis thaliana. The bridge does not appear to involve
      the inner membranes. Live imaging revealed stretching of the MOP bridge,
      demonstrating the flexibility of the outer membrane. Mitochondria frequently
      undergo fission and fusion. These observations raise the possibility that MOPs
      bridges have a role in these processes.

PMID- 27031263
TI  - Primary mucosal melanoma of the head and neck in Denmark, 1982-2012: Demographic
      and clinical aspects. A retrospective DAHANCA study.
AB  - Background The study was performed to determine the epidemiological, clinical,
      and histopathological characteristics and prognosis of primary mucosal melanoma
      of the head and neck (MMHN) in Denmark. Material and methods This was a national
      retrospective multicenter study of patients diagnosed with MMHN between 1982 and
      2012 in Denmark. Data were retrieved from national databases and patient records.
      Incidence trends were examined for the entire period. We prepared survival curves
      and performed univariate and multivariate analysis for the period 1992-2012 to
      identify possible prognostic factors. Results No significant trends in incidence
      were found in the study period. The three-year overall and disease-free survival
      rates for MMHN were 46.5% and 35.5%, respectively. Negative margins was an
      independent predictor of disease-free survival, and age below 65, absence of
      distant metastases, and low overall TNM stage were predictors of overall
      survival. Radiotherapy did not improve survival significantly. Recurrence rates
      were high, even for patients with negative margins. Conclusions MMHN remains a
      rare disease with a poor prognosis, particularly for patients aged over 65, those
      with distant metastasis, and those with advanced TNM stage. Importantly, the rate
      of recurrence is lowest in patients with negative margins. 

PMID- 27031264
TI  - A Simple Method for Measurement of Femoral Anteversion-Validation and Assessment
      of Reproducibility.
AB  - OBJECTIVES: To propose a simple method for measurement of femoral anteversion
      (AV) with a conventional fluoroscope, to evaluate the interobserver and
      intraobserver reliability of this method on the basis of human cadaver femurs,
      and to validate such method on the basis of computed tomography (CT). METHODS:
      Fourteen human cadavers with 28 intact femurs were included in the study. Three
      blinded observers measured femoral AV of the specimen with a fluoroscope. The
      session was repeated 8 weeks later and CT of the femurs were performed. Mean AV
      values and the difference between single and mean AV values were calculated.
      Interobserver/intraobserver reliability of the proposed method was assessed.
      Correlation between AV values measured with fluoroscope and CT was calculated.
      RESULTS: Mean AV was 18.1 degrees  when measured with fluoroscope and 19.2
      degrees  when measured with CT. Mean differences between single AV values were
      2.2 degrees  with fluoroscope and 2.5 degrees  with CT. The mean maximum observer
      variation per specimen was 8.8 degrees . Interobserver reliability was excellent
      (intraclass correlation coefficient: 0.853) and intraobserver reliability was
      good (intraclass correlation coefficient: 0.682). A high correlation was found
      between AV values measured with fluoroscope and CT (rho = 0.739, P < 0.01).
      CONCLUSION: The presented technique allows reliable and simple measurement of
      femoral AV with a conventional fluoroscope. The mean interobserver variation is
      comparable to what has been reported for CT. Maximum interobserver variation was
      <15 degrees  in all specimens. A clinical study will be necessary to prove the
      value of this technique for intraoperative adjustment of femoral AV according to
      the intact contralateral side.

PMID- 27031265
TI  - Iatrogenic Rhinoliths: Exercise Caution When Undertaking Palatal-Dental
      Impressions in the Cleft Patient With an Incompetent Palate.

PMID- 27031266
TI  - Outcomes of 44 Consecutive Complete Bilateral Cleft Lip and Palate Patients
      Treated With Secondary Alveolar Bone Grafting and Premaxillary Osteotomy.
AB  - OBJECTIVE: To report the surgical outcomes of secondary alveolar bone grafting
      with premaxillary osteotomy in a single surgeon cohort of complete bilateral
      cleft lip and palate patients. DESIGN: Retrospective review of 44 consecutive
      patients using hospital notes and radiographs. SETTING: Single specialist cleft
      lip and palate center, UK. PATIENTS: Consecutive patients with complete bilateral
      cleft lip and palate who were being treated with secondary alveolar bone grafting
      incorporating premaxillary osteotomy. OUTCOME MEASURES: Assessment of success of
      bone graft by Kindelan score; canine eruption; closure of fistulae and assessment
      of morbidity. RESULTS: Between January 6, 2000, and August 8, 2013, 44 patients
      with complete BCLP underwent secondary ABG with a premaxillary osteotomy as a one
      stage procedure. The mean follow-up was 7.3 years (range 1.4 to 14.6). Eighty
      five percent of ABGs were successful (a Kindelan score of 1 or 2), and canine
      eruption was 89%. Failure of the ABG occurred in 7%. Fistulae recurrence rate was
      11%, all of which were asymptomatic. No premaxillae were devitalized. CONCLUSION:
      Incorporating a premaxillary osteotomy into the secondary ABG surgical protocol
      can be a safe technique that gives excellent surgical exposure for fistula
      repair.

PMID- 27031267
TI  - De Novo 1.77-Mb Microdeletion of 10q22.2q22.3 in a Girl With Developmental Delay,
      Speech Delay, Congenital Cleft Palate, and Bilateral Hearing Impairment.
AB  - Interstitial deletions of chromosome band 10q22.1q22.3 are rare. We here report a
      2.5-year-old female patient with developmental delay, speech delay, congenital
      cleft palate, and bilateral hearing impairment. The girl's karyotype was normal.
      Chromosome microarray analysis (CMA) revealed a 1.77-Mb de novo interstitial
      deletion in 10q22.2q22.3. The deletion harbors 9 genes, including KAT6B, DUPD1,
      DUSP13, SAMD8, VDAC2, COMTD1, ZNF503, NCRNA00245, and C10orf11. This is the first
      patient with a deletion of the smallest size in 10q22.2q22.3 as detected using
      single nucleotide polymorphism (SNP) arrays. Comparisons with patients with
      overlapping deletions and in neighboring regions demonstrate the clinical impact
      of each deletion and in the context of other deletions within the 10q22q23
      region. Additionally, KAT6B and C10orf11 could represent disease-associated genes
      that contribute to developmental delay, speech and language delay, and congenital
      cleft palate.

PMID- 27031268
TI  - Velopharyngeal Structural and Functional Assessment of Speech in Young Children
      Using Dynamic Magnetic Resonance Imaging.
AB  - OBJECTIVE: The purpose of this study was to demonstrate a novel method for
      examining the velopharyngeal mechanism using static and dynamic magnetic
      resonance imaging (MRI) at the sentence-level production in young children with
      normal anatomy. This study examined whether velopharyngeal events occurring in
      the midsagittal plane are correlated to muscle events occurring along the plane
      of velopharyngeal closure. Adenoid involvement in velopharyngeal function was
      also explored. METHODS: A high-resolution, T2-weighted turbo-spin-echo three
      dimensional anatomical scan was used to acquire static velopharyngeal data and a
      fast-gradient echo fast low angle shot multishot spiral technique (15.8 frames
      per second) was used to acquire dynamic data on 11 children between 4 and 9 years
      old. RESULTS: Changes in velar knee height from rest to the bilabial /p/
      production was strongly correlated with changes in the velar configuration (r =
      0.680, P = .021) and levator muscle contraction (r = 0.703, P = .016). Velar
      configuration was highly correlated to levator muscle changes (r = 0.685, P =
      .020). Mean alpha angle during bilabial /p/ production was 176 degrees , which
      demonstrated that subjects achieve velopharyngeal closure at or just below the
      palatal plane. Subjects with a larger adenoid pad used significantly less (r = 
      0.660, P = .027) levator muscle contraction compared with individuals with
      smaller adenoids. CONCLUSIONS: This study demonstrates a potentially useful
      technique in dynamic MRI that does not rely on cyclic repetitions or sustained
      phonation. This study lends support to the clinical potential of dynamic MRI
      methods for cleft palate management.

PMID- 27031269
TI  - A Longitudinal Study of the Presence of Dental Anomalies in the Primary and
      Permanent Dentitions of Cleft Lip and/or Palate Patients.
AB  - OBJECTIVE: The aim is to survey primary and permanent dental anomalies:
      hypodontia, microdontia, a supernumerary tooth, and fused teeth in patients with
      cleft lip and/or palate. DESIGN: Retrospective longitudinal study Subjects :  The
      subjects were selected from all 1724 patients with cleft lip and/or palate who
      were registered at the orthodontic clinic of Kyushu University Hospital, Fukuoka,
      Japan, from 1970 to 2009. Finally, 994 subjects were evaluated for primary
      dentition, 1352 for permanent dentition, and 871 for the longitudinal changes
      from primary to permanent dentition. METHODS: The prevalence of dental anomalies
      was compared for each tooth type, among various cleft types, between males and
      females, and between the alveolar cleft area and the noncleft area. RESULTS: The
      prevalence of hypodontia was 16.2% for primary dentition and 52.7% for permanent
      dentition in the subjects with cleft lip and/or palate. Hypodontia increased with
      the severity of the cleft type. Multiple hypodontia was found more frequently in
      the subjects with bilateral cleft lip and palate and the subjects with unilateral
      cleft lip and palate. Microformed lateral incisors were found in 22.7% of
      permanent lateral incisors but not in primary dentition. Supernumerary teeth were
      found in 17.7% of the subjects with cleft lip and/or palate for primary maxillary
      dentition and in 5.7% for permanent maxillary dentition. CONCLUSION: The
      prevalence of hypodontia was greater in permanent dentition than in primary
      dentition; although, it was not much different between males and females or
      between the right and left sides. The prevalence of dental anomalies was
      significantly different among four groups by cleft type: cleft lip, cleft lip and
      alveolus, cleft lip and palate, and cleft palate.

PMID- 27031270
TI  - Children's Attitudes Toward Peers With Unintelligible Speech Associated With
      Cleft Lip and/or Palate.
AB  - OBJECTIVE: The objective of this study was to investigate whether reduced speech
      intelligibility in children with cleft palate affects social and personal
      attribute judgments made by typically developing children of different ages.
      DESIGN: The study (1) measured the correlation between intelligibility scores of
      speech samples from children with cleft palate and social and personal attribute
      judgments made by typically developing children based on these samples and (2)
      compared the attitude judgments made by children of different ages. Participants 
      A total of 90 typically developing children, 30 in each of three age groups (7
      to 8 years, 9 to 10 years, and 11 to 12 years). OUTCOME MEASURES: Speech
      intelligibility scores and typically developing children's attitudes were
      measured using eight social and personal attributes on a three-point rating
      scale. RESULTS: There was a significant correlation between the speech
      intelligibility scores and attitude judgments for a number of traits: "sick
      healthy" as rated by the children aged 7 to 8 years, "no friends-friends" by the
      children aged 9 to 10 years, and "ugly-good looking" and "no friends-friends" by
      the children aged 11 to 12 years. Children aged 7 to 8 years gave significantly
      lower ratings for "mean-kind" but higher ratings for "shy-outgoing" when compared
      with the other two groups. CONCLUSIONS: Typically developing children tended to
      make negative social and personal attribute judgments about children with cleft
      palate based solely on the intelligibility of their speech. Society, educators,
      and health professionals should work together to ensure that children with cleft
      palate are not stigmatized by their peers.

PMID- 27031271
TI  - New developments in proprotein convertase subtilisin-kexin 9's biology and
      clinical implications.
AB  - PURPOSE OF REVIEW: High levels of LDL-cholesterol (LDL-C) are directly associated
      with devastating cardiovascular complications. Statins downregulate cholesterol
      synthesis and upregulate hepatic mRNA levels of LDL receptor (LDLR) and
      proprotein convertase subtilisin-kexin 9 (PCSK9), a validated enhancer of LDLR
      protein degradation. Herein, we summarize recent discoveries of the biological
      properties of PCSK9 in both health and disease states. RECENT FINDINGS: PCSK9
      downregulation of the LDLR protein likely explains the observed protective effect
      of the loss of PCSK9 in reducing lipoprotein(a) and incidence of septic shock.
      Injectable inhibitory PCSK9 monoclonal antibodies are now prescribed to
      hypercholesterolemic patients that do not reach target levels of LDL-C with
      available drugs. PCSK9 also reduces the levels of other receptors, for example,
      VLDL receptor (VLDLR), ApoER2, CD36, and CD81. The efficacy of the upregulation
      of LDLR and VLDLR cell surface levels in the absence of PCSK9 is both tissue and
      sex dependent. As LDLR, CD81, and VLDLR are hepatitis C receptors, PCSK9 may
      protect against certain viral infections. SUMMARY: New functions of PCSK9 and
      other receptor targets are beginning to emerge to explain the observed changes in
      LDL-C and triglycerides. The effect of PCSK9 loss-of-function on glucose
      metabolism, factors that regulate the expression of PCSK9, and the roles of PCSK9
      in other tissues, for example, intestine, kidney, and brain require further
      investigations.

PMID- 27031273
TI  - Glucagon-like peptide-1, glucagon-like peptide-2, and lipid metabolism.
AB  - PURPOSE OF REVIEW: Glucagon-like peptide-1 (GLP-1) is the best known incretin
      hormone able to potentiate glucose-induced insulin secretion. Moreover, GLP-1 is
      currently under intensive investigation as a potential crucial mediator of
      beneficial metabolic effects after bariatric surgery, because of its eating
      inhibitory, antiobesity, and antidiabetes effects. This review briefly summarizes
      recent findings on the specific effects of GLP-1 on lipoprotein metabolism. The
      related hormone GLP-2 is derived from the same precursor gene; its effects on
      lipoprotein metabolism will also be discussed briefly. RECENT FINDINGS:
      Pharmacological activation of the GLP-1 system has beneficial effects on obesity
      induced alterations of lipoprotein metabolism. These benefits can be observed
      with direct GLP-1 receptor agonists like liraglutide or exendin-4, but also with
      inhibitors of dipeptidyl peptidase IV (DPP-IV), which reduce the breakdown of
      endogenous GLP-1. The role of GLP-2-related pathways on lipid levels and
      metabolism are less clear, but some effects (e.g. increased intestinal
      chylomicron output) are opposite to GLP-1. SUMMARY: Activation of the GLP-1
      dependent pathways may perhaps translate into a lower cardiovascular risk.
      Understanding how GLP-1 and GLP-2 regulate and interact in the control of
      lipoprotein metabolism will set the stage for the development of new strategies
      to treat dyslipidaemia in obesity, diabetes, and other cardiometabolic diseases.

PMID- 27031272
TI  - HDLs in crises.
AB  - PURPOSE OF REVIEW: The clinical utility of HDLs has been scrutinized upon the
      publication of Mendelian randomization studies showing no effect of HDL
      cholesterol (HDL-C) modifying variants on cardiovascular disease (CVD) outcome.
      The failures of randomized controlled HDL-C-directed intervention trials have
      further fueled this skepticism. This general criticism originates from
      oversimplification that has equated 'HDL-C' with 'HDL' and misconceived both as
      the 'good cholesterol'. RECENT FINDINGS: HDL particles are heterogeneous and
      carry hundreds of different lipids, proteins, and microRNAs. Many of them but not
      cholesterol, that is, HDL-C, contributes to the multiple protective functions of
      HDLs that probably evolved to manage potentially life-threatening crises.
      Inflammatory processes modify the composition of HDL particles as well as their
      individual protein and lipid components, and, as a consequence, also their
      functionality. Gain of dominant-negative functions makes dysfunctional HDL a part
      rather than a solution of the endangering situation. Quantification of HDL
      particle numbers, distinct proteins or lipids, and modifications thereof as well
      as bioassays of HDL functionality are currently explored toward their diagnostic
      performance in risk prediction and monitoring of treatment response. SUMMARY: Any
      successful clinical exploitation of HDLs will depend on the identification of the
      most relevant (dys)functions and their structural correlates. Stringent or
      prioritized structure-(dys)function relationships may provide biomarkers for
      better risk assessment and monitoring of treatment response. The most relevant
      agonists carried by either functional or dysfunctional HDLs as well as their
      cellular responders are interesting targets for drug development.

PMID- 27031274
TI  - Bile salts in control of lipid metabolism.
AB  - PURPOSE OF REVIEW: The view on bile salts has evolved over the years from being
      regarded as simple detergents that aid intestinal absorption of fat-soluble
      nutrients to being important hormone-like integrators of metabolism. This review
      provides an update on the rapidly developing field of interactions between bile
      salts and lipid metabolism, with a particular emphasis on the underlying
      mechanisms. RECENT FINDINGS: The nuclear receptor farnesoid X receptor (FXR)
      plays major roles in bile salt-mediated signaling pathways. The recent
      identification of novel FXR targets and factors involved in FXR signaling
      highlights the interactions of bile acids with lipid metabolism. Exciting data
      have been reported on the use of intestine-specific FXR agonists as well as
      antagonists. In addition, encouraging results for treatment of hepatic steatosis
      obtained with obeticholic acid in the FLINT trial underline the therapeutic
      potential of bile salt signaling and metabolism for the treatment of lipid
      disorders. SUMMARY: Modulation of FXR activity appears to be a potent target, not
      only for improving bile salt homeostasis, but also to improve lipid metabolism.
      Depending on the metabolic context both, FXR agonists as well as antagonists,
      could prove to be of therapeutic benefit.

PMID- 27031275
TI  - Role of lipoprotein lipase in lipid metabolism.
AB  - PURPOSE OF REVIEW: A major step in energy metabolism is hydrolysis of
      triacylglycerol-rich lipoproteins (TRLs) to release fatty acids that can be used
      or stored. This is accomplished by lipoprotein lipase (LPL) at 'binding lipolysis
      sites' at the vascular endothelium. A multitude of interactions are involved in
      this seemingly simple reaction. Recent advances in the understanding of some of
      these factors will be discussed in an attempt to build a comprehensive picture.
      RECENT FINDINGS: The first event in catabolism of TRLs is that they dock at the
      vascular endothelium. This requires LPL and GPIHBP1, the endothelial transporter
      of LPL.Kinetic studies in rats with labeled chylomicrons showed that once a
      chylomicron has docked in the heart it stays for minutes and a large number of
      triacylglycerol molecules are split. The distribution of binding between tissues
      reflects the amount of LPL, as evident from studies with mutant mice.Clearance of
      TRLs is often slowed down in metabolic disease, as was demonstrated both in mice
      and men. In mice, this was directly connected to decreased amounts of endothelial
      LPL. SUMMARY: The LPL system is central in energy metabolism and results from
      interplay between several factors. Rapid and exciting progress is being made.

PMID- 27031276
TI  - Atherosclerosis: the interplay between lipids and immune cells.
AB  - PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of mortality
      worldwide. The underlying cause of the majority of cardiovascular disease is
      atherosclerosis. In the past, atherosclerosis was considered to be the result of
      passive lipid accumulation in the vessel wall. However, today's picture of the
      pathogenesis of atherosclerosis is much more complex, with a key role for immune
      cells and inflammation in conjunction with hyperlipidemia, especially elevated
      (modified) LDL levels. Knowledge on immune cells and immune responses in
      atherosclerosis has progressed tremendously over the past decades, and the same
      is true for the role of lipid metabolism and the different lipid components.
      However, it is largely unknown how lipids and the immune system interact. In this
      review, we will describe the effect of lipids on immune cell development and
      function, and the effects of immune cells on lipid metabolism. RECENT FINDINGS:
      Recently, novel data have emerged that show that immune cells are affected, and
      behave differently in a hyperlipidemic environment. Moreover, immune cells have
      reported to be able to affect lipid metabolism. SUMMARY: In this review, we will
      summarize the latest findings on the interactions between lipids and the immune
      system, and we will discuss the potential consequences of these novel insights
      for future therapies for atherosclerosis.

PMID- 27031277
TI  - The multifaceted interplay between lipids and epigenetics.
AB  - PURPOSE OF REVIEW: The interplay between lipids and epigenetic mechanisms has
      recently gained increased interest because of its relevance for common diseases
      and most notably atherosclerosis. This review discusses recent advances in
      unravelling this interplay with a particular focus on promising approaches and
      methods that will be able to establish causal relationships. RECENT FINDINGS:
      Complementary approaches uncovered close links between circulating lipids and
      epigenetic mechanisms at multiple levels. A characterization of lipid-associated
      genetic variants suggests that these variants exert their influence on lipid
      levels through epigenetic changes in the liver. Moreover, exposure of monocytes
      to lipids persistently alters their epigenetic makeup resulting in more
      proinflammatory cells. Hence, epigenetic changes can both impact on and be
      induced by lipids. SUMMARY: It is the combined application of technological
      advances to probe epigenetic modifications at a genome-wide scale and
      methodological advances aimed at causal inference (including Mendelian
      randomization and integrative genomics) that will elucidate the interplay between
      circulating lipids and epigenetics. Understanding its role in the development of
      atherosclerosis holds the promise of identifying a new category of therapeutic
      targets, since epigenetic changes are amenable to reversal.

PMID- 27031278
TI  - Expansile Maxillary Sinus Mass in a Young Child.

PMID- 27031279
TI  - A family with factor X deficiency from Argentina: a compound heterozygosis
      because of the combination of a new mutation (Gln138Arg) with an already known
      one (Glu350Lys).
AB  - The objective was to investigate a family from Argentina. The proposita was a 51
      year-old woman who had a moderate bleeding tendency. Some of her children showed
      a mild bleeding tendency. Her mother and the husband were asymptomatic. Clotting,
      immunological and molecular biology techniques were used. Partial thromboplastin,
      prothrombin, Russell Viper venom-clotting times were moderately prolonged in the
      proposita, whereas they were slightly prolonged in the children and in her
      mother. Factor X (FX) activity was about 2-3% of normal in all assay systems. FX
      antigen was less than 5%. Other clotting factors and platelet were normal.
      Genetic analysis showed a compound heterozygosis: combination of a 'new' mutation
      (Gln138Arg) with an already known mutation (Glu350Lys). The children had
      intermediate FX levels (35-63% of normal) and were carriers of one of the two
      mutations present in the proposita. This is the first observation of a FX
      deficiency in Argentina. 

PMID- 27031280
TI  - Investigating the Familial Basis of Heightened Risk-Taking in Adolescents With
      Conduct Disorder and Their Unaffected Relatives.
AB  - Previous studies have demonstrated increased risk-taking in adolescents with
      Conduct Disorder (CD) compared with typically developing controls. Increased risk
      taking may partly mediate the pathway from genetic or environmental risk to CD.
      We investigated the familial basis of risk-taking by examining whether the
      unaffected relatives of CD probands (n = 22) showed heightened risk-taking in a
      gambling task, in common with affected probands (n = 44). Adolescents with CD
      were more likely to select risky options than the typically developing controls
      (n = 37) and unaffected relatives. Our findings confirm the association between
      CD and increased risk-taking, but suggest that this decision-making style may not
      have a familial basis.

PMID- 27031281
TI  - Group B and F Beta Streptococcus Necrotizing Infection-Surgical Challenges with a
      Deep Central Plantar Space Abscess A Diabetic Limb Salvage Case Report.
AB  - We present the case of a 66-year-old, type II diabetic male with a deep wound to
      the plantar-lateral aspect of his right hallux. On examination, the central
      plantar compartment of his right foot was moderately erythematous and tender on
      palpation. After obtaining a deep wound culture, treatment was complicated by a
      progression of a group B and F beta streptococcus, necrotizing infection. The
      patient underwent a right hallux amputation, followed by a plantar medial
      incision for drainage of an abscess to the medial and central plantar
      compartments of the foot. Due to the extent and limb threat of the infection, the
      patient ultimately underwent a transmetatarsal amputation. Advanced healing
      modalities were also employed to decrease wound healing times, which allowed the
      patient to achieve early weightbearing and return to activities of daily living.
      This study depicts how the astute podiatric surgeon needs to make a decision in a
      timely manner to surgically debride all nonviable and necrotic tissue in order to
      minimize further amputation and preserve foot function. 

PMID- 27031282
TI  - Biosecurity and Health Monitoring at the Zebrafish International Resource Center.
AB  - The Zebrafish International Resource Center (ZIRC) is a repository and
      distribution center for mutant, transgenic, and wild-type zebrafish. In recent
      years annual imports of new zebrafish lines to ZIRC have increased tremendously.
      In addition, after 15 years of research, we have identified some of the most
      virulent pathogens affecting zebrafish that should be avoided in large production
      facilities, such as ZIRC. Therefore, while importing a high volume of new lines
      we prioritize safeguarding the health of our in-house fish colony. Here, we
      describe the biosecurity and health-monitoring program implemented at ZIRC. This
      strategy was designed to prevent introduction of new zebrafish pathogens,
      minimize pathogens already present in the facility, and ensure a healthy
      zebrafish colony for in-house uses and shipment to customers.

PMID- 27031284
TI  - Self-Assembly and Critical Aggregation Concentration Measurements of ABA Triblock
      Copolymers with Varying B Block Types: Model Development, Prediction, and
      Validation.
AB  - The dissipative particle dynamics (DPD) simulation technique is a coarse-grained
      (CG) molecular dynamics-based approach that can effectively capture the
      hydrodynamics of complex systems while retaining essential information about the
      structural properties of the molecular species. An advantageous feature of DPD is
      that it utilizes soft repulsive interactions between the beads, which are CG
      representation of groups of atoms or molecules. In this study, we used the DPD
      simulation technique to study the aggregation characteristics of ABA triblock
      copolymers in aqueous medium. Pluronic polymers (PEG-PPO-PEG) were modeled as two
      segments of hydrophilic beads and one segment of hydrophobic beads. Tyrosine
      derived PEG5K-b-oligo(desaminotyrosyl tyrosine octyl ester-suberate)-b-PEG5K
      (PEG5K-oligo(DTO-SA)-PEG5K) block copolymers possess alternate rigid and flexible
      components along the hydrophobic oligo(DTO-SA) chain, and were modeled as two
      segments of hydrophilic beads and one segment of hydrophobic, alternate soft and
      hard beads. The formation, structure, and morphology of the initial aggregation
      of the polymer molecules in aqueous medium were investigated by following the
      aggregation dynamics. The dimensions of the aggregates predicted by the
      computational approach were in good agreement with corresponding results from
      experiments, for the Pluronic and PEG5K-oligo(DTO-SA)-PEG5K block copolymers. In
      addition, DPD simulations were utilized to determine the critical aggregation
      concentration (CAC), which was compared with corresponding results from an
      experimental approach. For Pluronic polymers F68, F88, F108, and F127, the
      computational results agreed well with experimental measurements of the CAC
      measurements. For PEG5K-b-oligo(DTO-SA)-b-PEG5K block polymers, the complexity in
      polymer structure made it difficult to directly determine their CAC values via
      the CG scheme. Therefore, we determined CAC values of a series of triblock
      copolymers with 3-8 DTO-SA units using DPD simulations, and used these results to
      predict the CAC values of triblock copolymers with higher molecular weights by
      extrapolation. In parallel, a PEG5K-b-oligo(DTO-SA)-b-PEG5K block copolymer was
      synthesized, and the CAC value was determined experimentally using the pyrene
      method. The experimental CAC value agreed well with the CAC value predicted by
      simulation. These results validate our CG models, and demonstrate an avenue to
      simulate and predict aggregation characteristics of ABA amphiphilic triblock
      copolymers with complex structures.

PMID- 27031283
TI  - Structural and kinetic analysis of the COP9-Signalosome activation and the cullin
      RING ubiquitin ligase deneddylation cycle.
AB  - The COP9-Signalosome (CSN) regulates cullin-RING ubiquitin ligase (CRL) activity
      and assembly by cleaving Nedd8 from cullins. Free CSN is autoinhibited, and it
      remains unclear how it becomes activated. We combine structural and kinetic
      analyses to identify mechanisms that contribute to CSN activation and Nedd8
      deconjugation. Both CSN and neddylated substrate undergo large conformational
      changes upon binding, with important roles played by the N-terminal domains of
      Csn2 and Csn4 and the RING domain of Rbx1 in enabling formation of a high
      affinity, fully active complex. The RING domain is crucial for deneddylation, and
      works in part through conformational changes involving insert-2 of Csn6. Nedd8
      deconjugation and re-engagement of the active site zinc by the autoinhibitory
      Csn5 glutamate-104 diminish affinity for Cul1/Rbx1 by ~100-fold, resulting in its
      rapid ejection from the active site. Together, these mechanisms enable a dynamic
      deneddylation-disassembly cycle that promotes rapid remodeling of the cellular
      CRL network.

PMID- 27031286
TI  - Insights into How Cyclic Peptides Switch Conformations.
AB  - Cyclic peptides have recently emerged as promising modulators of protein-protein
      interactions. However, it is currently highly difficult to predict the structures
      of cyclic peptides owing to their rugged conformational free energy landscape,
      which prevents sampling of all thermodynamically relevant conformations. In this
      article, we first investigate how a relatively flexible cyclic hexapeptide
      switches conformations. It is found that, although the circular geometry of small
      cyclic peptides of size 6-8 may require rare, coherent dihedral changes to sample
      a new conformation, the changes are rather local, involving simultaneous changes
      of phii and psii or psii and phii+1. The understanding of how these cyclic
      peptides switch conformations enables the use of metadynamics simulations with
      reaction coordinates specifically targeting such coupled two-dihedral changes to
      effectively sample cyclic peptide conformational space. 

PMID- 27031285
TI  - Reliability of spot-check transcutaneous hemoglobin measurement in children.
AB  - BACKGROUND: This study investigated the correlation between spot-check
      transcutaneous hemoglobin (Hb) and simultaneously measured venous Hb in children.
      METHODS: Two hundred and seventeen children weighing 10-30 kg in whom complete
      blood count had been obtained for any reason were enrolled in this study.
      Demographic characteristics and vital signs were recorded. Prior to taking blood
      samples, transcutaneous Hb, heart rate, oxygen saturation, and perfusion index
      were measured using a probe connected to the subject's thumb. To determine the
      reliability of the transcutaneous measurement versus venous blood measurement
      performed via an autoanalyzer device, interclass correlation coefficient (ICC)
      was calculated. The correlation between the two measurements was evaluated on
      Bland-Altman analysis. RESULTS: A total of 59.4% of the patients were boys. The
      average age was 53 months (range, 6-132 months). Average bodyweight was 16 kg
      (range, 10-25 kg). Mean venous Hb, hematocrit, and transcutaneous Hb were 11.94
      +/- 1.15 g/dL, 35.8 +/- 3.2%, and 12.42 +/- 1.24 g/dL, respectively. The ICC for
      the reliability of the transcutaneous measurements versus venous blood
      measurements was r = 0.67 (95%CI: 0.5776-0.7526). The correlation between the two
      sets of measurements was good, as evaluated by the Bland-Altman analysis.
      CONCLUSION: There is good correlation between transcutaneous and venous blood
      measurements of Hb. In the future, transcutaneous measurement, as a non-invasive
      method, may be an alternative for the measurement of Hb in childhood.

PMID- 27031287
TI  - Cbeta-H stretching vibration as a new probe for conformation of n-propanol in
      gaseous and liquid states.
AB  - The development of potential probes to identify molecular conformation is
      essential in organic and biological chemistry. In this work, we investigated a
      site-specific C-H stretching vibration as a conformational probe for a model
      compound, 1,1,3,3,3-deuterated n-propanol (CD3CH2CD2OH), using stimulated
      photoacoustic Raman spectroscopy in the gas phase and conventional spontaneous
      Raman spectroscopy in the liquid state. Along with quantum chemistry
      calculations, the experiment shows that the CH2 symmetric stretching mode at the
      beta-carbon position is very sensitive to the conformational structure of n
      propanol and can serve as a new probe for all five of its conformers. Compared
      with the O-H stretching vibration, a well-established conformational sensor for n
      propanol, the Cbeta-H stretching vibration presented here shows better
      conformational resolution in the liquid state. Furthermore, using this probe, we
      investigated the conformational preference of n-propanol in pure liquid and in
      dilute water solution. It is revealed that in pure liquid, n-propanol molecules
      prefer the trans-OH conformation, and in dilute water solution, this preference
      is enhanced, indicating that the water molecules play a role of further
      stabilizing the trans-OH n-propanol conformers. This leads to conformational
      evolution that n-propanol molecules with gauche-OH structure are transferred to
      the trans-OH structure upon diluting with water. These results not only provide
      important information on structures of n-propanol in different environments, but
      also demonstrate the potential of the C-H stretching vibration as a new tool for
      conformational analysis. This is especially important when considering that
      hydrocarbon chains are structural units in organic and biological molecules.

PMID- 27031288
TI  - Mitochondrial dysfunction bridges negative affective disorders and cardiomyopathy
      in socially isolated rats: Pros and cons of fluoxetine.
AB  - Objectives Depression is tightly associated with cardiovascular comorbidity and
      accounts for high financial and social burden worldwide. Mitochondrial
      dysfunction contributes to the pathophysiology of depression and cardiovascular
      disorders; its contribution to depression-cardiovascular comorbidity has not yet
      been investigated. Methods Adolescent rats were subjected to 4 weeks of isolation
      (social isolation stress or SIS) or social conditions (control), and then they
      were divided into treatment (fluoxetine, 7.5 mg/kg/day for 21 days) and non
      treatment groups. After different housing conditions and treatment, animals were
      evaluated by behavioural tests (n = 6-8) and mitochondrial assessments (n = 3) of
      brain and cardiac tissues. Results We found that juvenile SIS induced behavioural
      abnormalities and mitochondrial dysfunction in adulthood. We showed that juvenile
      SIS was associated with impaired respiratory chain complex, which leads to
      reactive oxygen species formation, oxidative damage and ATP abatement in both
      brain and heart. Administration of FLX (7.5 mg/kg/day) during the isolation
      period attenuated the effects of SIS on the brain mitochondria and behavioural
      abnormalities, but had little or no effect on SIS-induced mitochondrial
      dysfunction in cardiac tissue. Conclusions This suggests that juvenile SIS
      predisposes the co-occurrence of depression and cardiovascular disease through
      mitochondrial dysfunction and that therapeutic effect of fluoxetine is partly
      mediated by its effect on mitochondrial function.

PMID- 27031289
TI  - The role of obesity measures in the development and persistence of major
      depressive disorder.
AB  - BACKGROUND: The role of obesity with the development of major depressive disorder
      (MDD) requires conformation and whether obesity contributes to more chronic
      depression in persons with established (MDD) is unknown. This study examined the
      longitudinal relationship of body mass index (BMI) and waist circumference with
      the incidence and persistence of MDD over 2-year and 6-year periods. METHOD: Data
      were sourced from the Netherlands Study of Depression and Anxiety. MDD was
      established with Composite International Diagnostic Interviews. The relationship
      of BMI and waist circumference with the development of depression two and six
      years later were estimated in the subsample with no current psychopathology at
      baseline. Associations with the persistence of depression was estimated in the
      subsample with current MDD. RESULTS: Higher BMI at baseline, but not waist
      circumference, slightly increased the odds of the development of MDD after two
      years (odds ratio (OR) per standard deviation increase: 1.11; p=0.03), This
      relationship was not significant after adjustment for health and lifestyle
      variables. Conversely, over a 6-year period both BMI and waist circumference
      moderately increased the odds of developing MDD even after adjustment (OR:1.17;
      p=0.05, OR:1.20; p=0.05). Persistence of MDD in currently depressed subjects, is
      not related with BMI or waist circumference (adjusted OR:0.93; p=0.2, OR:0.91;
      p=0.15). LIMITATIONS: Development of depression may differ in participants lost
      to follow-up. CONCLUSION: Over a 6 year period, patients with higher BMI show a
      slightly increased risk of development of depression. However, in depressed
      patients there is no relationship between BMI and the persistence of depression.

PMID- 27031290
TI  - Similarities between emotional dysregulation in adults suffering from ADHD and
      bipolar patients.
AB  - BACKGROUND: Emotional dysregulation in subjects with attention deficit and
      hyperactivity disorder (ADHD) is a topic of growing interest among clinicians and
      researchers. The present study aims at investigating components of emotional
      dysregulation in adults ADHD compared to subjects suffering from bipolar disorder
      (BD). METHODS: A total of 150 adults ADHD, 335 adults BD subjects and 48 controls
      were assessed using the Affective Lability Scale (ALS) and the Affect Intensity
      Measure (AIM), measuring respectively emotion lability and emotion
      responsiveness. RESULTS: ADHD and BD subjects scored significantly higher on the
      ALS compared to controls (p=0.0001). BD subjects scored above ADHD ones (3.07
      (SD=0.66) vs. 2.30 (SD=0.68); p<0.0001). The average total scores achieved on the
      AIM were significantly different for the three groups (p=0.0001) with
      significantly higher scores for ADHD subjects compared to BD ones (3.74 (SD=0.59)
      vs. 3.56 (SD=0.69); p<0.0001). LIMITATIONS: Suspected cases of ADHD in the BD and
      control groups were derived from the Wender Utah Rating Scale (WURS). This study
      is a retrospective one. CONCLUSION: Our study thus highlights the importance of
      emotional dysregulation in adults suffering from ADHD, showing that they display
      higher emotional intensity than bipolar disorder subjects and controls. Although
      the current diagnostic criteria of ADHD do not contain an emotional dimension, a
      better recognition of the significance of emotional responsiveness in ADHD
      patients can improve the care afforded to these patients, beyond the inattentive
      and hyperactive/impulsive components.

PMID- 27031291
TI  - MicroRNA-495 Regulates Migration and Invasion in Prostate Cancer Cells Via
      Targeting Akt and mTOR Signaling.
AB  - Abnormal microRNA (miR) expressions were implicated in prostate cancer
      progression. We identified a novel miR-495, which was downregulated in prostate
      cancer, but not normal prostate cell lines. MiR-495 directly targeted the 3'-UTR
      of Akt and mTOR mRNAs. Expression of miR-495 in prostate cancer cells
      significantly downregulated Akt and mTOR, which further inhibited cancer cell
      proliferation, migration, and invasion in vitro. Function of miR-495 in vivo was
      examined in mouse xenograft model and was found to significantly inhibit the
      growth of tumors, mediated by repressing Akt and mTOR. Our report supported miR
      495 as a novel tumor suppressor microRNA in prostate cancer. 

PMID- 27031292
TI  - Brief Report: Rethinking Data Collection for HIV Prevention Trials.
AB  - There is a strong push to conduct large-scale randomized controlled study designs
      in HIV prevention studies. In these randomized controlled studies, the primary
      research objective is typically to determine the treatment effect based on some
      biological outcome (eg, HIV infection). But many unused self-reported outcomes
      are also being collected. We illustrate the extent of this problem using the
      EXPLORE data as an example.

PMID- 27031293
TI  - Functions, structures, and applications of cellobiose 2-epimerase and glycoside
      hydrolase family 130 mannoside phosphorylases.
AB  - Carbohydrate isomerases/epimerases are essential in carbohydrate metabolism, and
      have great potential in industrial carbohydrate conversion. Cellobiose 2
      epimerase (CE) reversibly epimerizes the reducing end d-glucose residue of beta
      (1->4)-linked disaccharides to d-mannose residue. CE shares catalytic machinery
      with monosaccharide isomerases and epimerases having an (alpha/alpha)6-barrel
      catalytic domain. Two histidine residues act as general acid and base catalysts
      in the proton abstraction and addition mechanism. beta-Mannoside hydrolase and 4
      O-beta-d-mannosyl-d-glucose phosphorylase (MGP) were found as neighboring genes
      of CE, meaning that CE is involved in beta-mannan metabolism, where it epimerizes
      beta-d-mannopyranosyl-(1->4)-d-mannose to beta-d-mannopyranosyl-(1->4)-d-glucose
      for further phosphorolysis. MGPs form glycoside hydrolase family 130 (GH130)
      together with other beta-mannoside phosphorylases and hydrolases. Structural
      analysis of GH130 enzymes revealed an unusual catalytic mechanism involving a
      proton relay and the molecular basis for substrate and reaction specificities.
      Epilactose, efficiently produced from lactose using CE, has superior
      physiological functions as a prebiotic oligosaccharide. 

PMID- 27031294
TI  - Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes
      Mellitus.
AB  - Fibroblast growth factor (FGF) 21 is a distinctive member of the FGF family that
      functions as an endocrine factor. It is expressed predominantly in the liver, but
      is also found in adipose tissue and the pancreas. Pharmacological studies have
      shown that FGF21 normalizes glucose and lipid homeostasis, thereby preventing the
      development of metabolic disorders, such as obesity and diabetes. Despite growing
      evidence for the therapeutic potential of FGF21, paradoxical increases of FGF21
      in different disease conditions point to the existence of FGF21 resistance. In
      this review, we give a critical appraisal of recent advances in the understanding
      of the regulation of FGF21 production under various physiological conditions, its
      antidiabetic actions, and the clinical implications. We also discuss recent
      preclinical and clinical trials using engineered FGF21 analogs in the management
      of diabetes, as well as the potential side effects of FGF21 therapy.

PMID- 27031295
TI  - Ammonia removal from raw manure digestate by means of a turbulent mixing
      stripping process.
AB  - In this study, ammonia stripping by means of a turbulent mixing process followed
      by pH neutralization was investigated as a simple and cost-effective ammonia
      removal technique to treat raw manure digestate. Batch tests conducted using CaO,
      NaOH and H2O2 to control pH and temperature and combinations thereof showed that
      sodium hydroxide was the most suitable chemical, as it is easy to handle,
      minimizes treatment time and costs, does not increase the solid content of the
      sludge and allows to easily control the stripping process. NaOH dosage mainly
      depended on buffering capacity rather than on total solid content. The analysis
      of the ammonia stripping process indicated that ammonia removal was strongly
      dependent on pH, and ammonia removal rate followed the pseudo-first-order
      kinetics. Total solid content slightly influenced TAN removal efficiency. When
      NaOH was applied to treat raw digestate at pH 10 and mean temperature of 23 +/- 2
      degrees C, TAN removal efficiency reached 88.7% after 24 h of turbulent mixing
      stripping, without reaching inhibitory salinity levels. Moreover, pH
      neutralization with sulfuric acid following the stripping process improved raw
      digestate dewaterability. 

PMID- 27031296
TI  - Biotic and abiotic controls on nitrogen leaching losses into waterways during
      successive bovine urine application to soil.
AB  - Cattle waste products high in nitrogen (N) that enter waterways via rainfall
      runoff can contribute to aquatic ecosystem health deterioration. It is well
      established that N leaching from this source can be reduced by plant
      assimilation, e.g. pasture grass. Additionally, N leaching can be reduced when
      there is sufficient carbon (C) in the soil such as plant litterfall to stimulate
      microbial processes, i.e. denitrification, which off-gas N from the soil profile.
      However, the relative importance of these two processes is not well understood. A
      soil microcosm experiment was conducted to determine the role of biotic
      processes, pasture grass and microbial activity, and abiotic processes such as
      soil sorption, in reducing N leaching loss, during successive additions of bovine
      urine. Pasture grass was the most effective soil cover in reducing N leaching
      losses, which leached 70% less N compared to exposed soil. Successive application
      of urine to the soil resulted in N accumulation, after which there was a breaking
      point indicated by high N leaching losses. This is likely to be due to the low
      C:N ratio within the soil profiles treated with urine (molar ratio 8:1) compared
      to water treated soils (30:1). In this experiment we examined the role of C
      addition in reducing N losses and showed that the addition of glucose can
      temporarily reduce N leaching. Overall, our results demonstrated that plant
      uptake of N was a more important process in preventing N leaching than microbial
      processes. 

PMID- 27031297
TI  - Development of a phantom and assessment of (141)Ce as a surrogate radionuclide
      for flood field uniformity testing of gamma cameras.
AB  - This paper describes an indigenous method for development and deployment of
      rechargeable liquid filled phantom with newly proposed radionuclide (141)Ce for
      determination of extrinsic uniformity of gamma cameras. Details about design of
      phantom, neutron irradiation of cerium targets, chemical processing of (141)Ce,
      charging of phantom with (141)Ce solution and their performance evaluation are
      presented. Suitability of (141)Ce in quality assurance of gamma cameras used in
      in-vivo diagnostic imaging procedures has been amply demonstrated.

PMID- 27031298
TI  - Epstein-Barr virus-associated B-cell lymphoproliferative disorder in a patient
      with Sezary syndrome treated by methotrexate.

PMID- 27031299
TI  - Diagnosis of a mucinous pancreatic cyst and resection of an intracystic nodule
      using a novel through-the-needle micro forceps.

PMID- 27031300
TI  - On The Latest Three-Stage Development of Nanomedicines based on Upconversion
      Nanoparticles.
AB  - Following the "detect-to-treat" strategy, by biological engineering, the emerging
      upconversion nanoparticles (UCNPs) have become one of the most promising
      inorganic nanomedicines, and their biomedical applications have gradually shifted
      from multimodal tumor imaging to highly efficient cancer therapy. The past few
      years have witnessed a three-stage development of UCNP-based nanomedicines. On
      one hand, UCNPs can optimize each clinical treatment tool (chemotherapy,
      photodynamic therapy (PDT), radiotherapy (RT)) by controlled drug
      delivery/release, near-infrared (NIR)-excited deep PDT, and radiosensitization,
      respectively, all of which contribute greatly to the optimized treatment efficacy
      along with minimized side effects. On the other hand, several individual
      treatments can be "smartly" integrated into a single UCNP-based nanotheranostic
      system for multimodal synergetic therapy, which can further improve the overall
      therapeutic effectiveness. Especially, UCNPs provide more-effective strategies
      for overcoming tumor hypoxia, thus leading to an ideal treatment efficacy for
      complete eradication of solid tumors. Finally, the critical issues regarding the
      future development of UCNPs are discussed to promote the clinic-translational
      applications of UCNP-based nanomedicines, as well as realization of our "one drug
      fits all" dream. 

PMID- 27031302
TI  - Ontogenetic variations in the diet of two invasive gobies, Neogobius melanostomus
      (Pallas, 1814) and Ponticola kessleri (Gunther, 1861), from the middle Danube
      (Slovakia) with notice on their potential impact on benthic invertebrate
      communities.
AB  - In this study, ontogenetic variations in diet of invasive bighead goby Ponticola
      kessleri and round goby Neogobius melanostomus from the middle Danube were
      analysed. Index of stomach fullness, Fulton's condition factor, index of food
      importance, frequency of occurrence, biomass, electivity, and proportions of
      invasive organisms in their diet were examined. Changes in the diet during
      ontogeny of both species emphasise the differences in their trophic niches. Our
      results combined with literary data suggest that bighead goby may threaten small
      native benthic fish species as a predator (especially in the invasion front),
      whereas round goby can potentially impact native fish species of all ontogenetic
      phases by competing for food. Round goby appear to have strong impact on
      bivalves, especially in the invasion front. High consumption of invasive
      organisms by bighead goby may help the native macroinvertebrate community. Thus,
      in contrast to round goby, bighead goby does not seem to be a hot candidate for
      being a nuisance invader.

PMID- 27031303
TI  - Characteristics of carbonaceous aerosols: Impact of biomass burning and secondary
      formation in summertime in a rural area of the North China Plain.
AB  - To determine the characteristics of carbonaceous aerosols in rural areas of the
      North China Plain, field measurements were conducted at Yucheng (YC) in the
      summers of 2013 and 2014. The concentrations of carbonaceous aerosols at YC
      exhibited clear diurnal variation, with higher concentrations in the early
      morning and at night and lower concentrations during the afternoon hours. The
      mass-balance method designed for particulate matter smaller than 2.5MUm (PM2.5)
      was used to calculate the organic matter (OM)/organic carbon (OC) ratio. The
      value obtained, 2.07+/-0.05, was suggested as a reference to estimate organics in
      PM2.5 in rural areas of the North China Plain. Biomass burning was identified to
      be a significant source of carbonaceous aerosols; approximately half of the
      samples obtained at YC were affected by biomass burning during summer 2013. Case
      studies revealed that biomass burning accounted for up to 52.6% of the OC and
      51.1% of the elemental carbon in PM2.5 samples. The organic coatings observed on
      sulphur-rich and potassium-rich particles indicated the formation of secondary
      organic aerosols (SOA) from the oxidation of precursor volatile organic compounds
      (VOCs) during the aging of smoke released from biomass burning. Based on the
      evolution of the VOCs, the contribution of VOCs oxidation to SOA concentration
      was 3.21 and 1.07MUgm(-3)ppm(-1) CO under conditions of low nitrogen oxide (NOx)
      and high NOx, respectively. Aromatics (e.g. benzene, toluene, xylene and
      ethylbenzene) made the greatest contribution to SOA concentration (88.4% in low
      NOx conditions and 80.6% in high-NOx conditions). The results of the study offer
      novel insights into the effects of biomass burning on the carbonaceous aerosols
      and SOA formation in polluted rural areas.

PMID- 27031301
TI  - Factors Influencing Health Facility Delivery in Predominantly Rural Communities
      across the Three Ecological Zones in Ghana: A Cross-Sectional Study.
AB  - BACKGROUND: Maternal and neonatal mortality indicators remain high in Ghana and
      other sub-Saharan African countries. Both maternal and neonatal health outcomes
      improve when skilled personnel provide delivery services within health
      facilities. Determinants of delivery location are crucial to promoting health
      facility deliveries, but little research has been done on this issue in Ghana.
      This study explored factors influencing delivery location in predominantly rural
      communities in Ghana. METHODS: Data were collected from 1,500 women aged 15-49
      years with live or stillbirths that occurred between January 2011 and April 2013.
      This was done within the three sites operating Health and Demographic
      Surveillance Systems, i.e., the Dodowa (Greater Accra Region), Kintampo (Brong
      Ahafo Region), and Navrongo (Upper-East Region) Health Research Centers in Ghana.
      Multivariable logistic regression was used to identify the determinants of
      delivery location, controlling for covariates that were statistically significant
      in univariable regression models. RESULTS: Of 1,497 women included in the
      analysis, 75.6% of them selected health facilities as their delivery location.
      After adjusting for confounders, the following factors were associated with
      health facility delivery across all three sites: healthcare provider's influence
      on deciding health facility delivery, (AOR = 13.47; 95% CI 5.96-30.48), place of
      residence (AOR = 4.49; 95% CI 1.14-17.68), possession of a valid health insurance
      card (AOR = 1.90; 95% CI 1.29-2.81), and socio-economic status measured by wealth
      quintiles (AOR = 2.83; 95% CI 1.43-5.60). CONCLUSION: In addition to known
      factors such as place of residence, socio-economic status, and possession of
      valid health insurance, this study identified one more factor associated with
      health facility delivery: healthcare provider's influence. Ensuring care
      provider's counseling of clients could improve the uptake of health facility
      delivery in rural communities in Ghana.

PMID- 27031304
TI  - Effects of therapy on masseter activity and chewing kinematics in patients with
      unilateral posterior crossbite.
AB  - OBJECTIVE: To describe the effects of therapy on masseter activity and chewing
      kinematic in patients with unilateral posterior crossbite (UPC). DESIGN: Fifty
      children (age: mean +/- SD: 9.1 +/- 2.3 years) with UPC (34 on the right side, 16
      on the left side) and twenty children (age: 9.5 +/- 2.6 years) with normal
      occlusion were selected for the study. The mandibular motion and the muscular
      activity during chewing soft and hard boli were simultaneously recorded, before
      and after correction with function generating bite, after a mean treatment time
      of 7.3 +/- 2.4 months plus the retention time of 5-6 months. The percentage of
      reverse cycles and the percent difference between ipsilateral and contralateral
      peaks of the masseter electromyography envelopes were computed. RESULTS: Before
      therapy, the percentage of reverse cycles during chewing on the crossbite side
      was greater in patients than in controls (P<0.001) and significantly reduced
      after therapy (P<0.001) towards the reference normal value (soft bolus; pre: 57
      +/- 30%, post:12 +/- 17%; hard bolus; pre: 65 +/- 34%, post: 12 +/- 13%;
      reference value: soft bolus 4 +/- 2%, hard bolus 5 +/- 3%). Before therapy the
      percent difference between electromyography envelope peaks in patients was lower
      than in controls (P<0.01) and significantly increased after therapy (P<0.05)
      becoming similar to the reference normal value. CONCLUSIONS: The correction
      induced a normal-like coordination of masseter muscles activity together with a
      significant reduction of the reverse chewing patterns. The previous altered
      muscular activation corresponded to the altered kinematics of reverse chewing
      cycles that might be considered a useful indicator of the severity of the
      masticatory function involvement.

PMID- 27031306
TI  - Nectin-1 and HVEM: cellular receptors for HSV-1 in skin.

PMID- 27031305
TI  - The role of TGF-beta1 in osteoarthritis of the temporomandibular joint in two
      genetic mouse models.
AB  - OBJECTIVE: The objective of this study is to elucidate osteoarthritis (OA)
      progression in the temporomandibular joint (TMJ) in two genetic mouse models by
      assessing the expression of an identified inflammatory marker associated with OA,
      viz., Tgf-beta1. This study provides mechanistic insight into disease progression
      based on the temporal expression of Tgf-beta1 in the TMJ. DESIGN: The two models
      included the heterozygous chondrodysplasia mutation (cho/+), a Coll11a1 mutation,
      and the autosomal semidominant disproportionate micromelia mutation (Dmm/+), a
      Col2a1 mutation. To determine OA status histologically, TMJs from each mutant
      were fixed, sectioned and stained with Safranin O to identify proteoglycans in
      condylar cartilage and counterstained with Fast Green. The extent of staining and
      onset of OA-like changes were quantified using the Modified Mankin scoring
      system. Using immunofluorescence, selected tissue sections of each genotype were
      stained for the presence of Tgf-beta1, HtrA1, and p-Smad2. RESULTS: The results
      revealed Mankin scores of the condylar cartilage of both mutants that are
      consistent with established histopathological changes of OA. Immunofluorescence
      indicated increased expression of all three molecular markers and their co
      localization within condylar chondrocytes of both mutants. CONCLUSIONS: Elevated
      Tgf-beta1 expression in mutant condylar cartilage supports the hypothesis that
      this inflammatory mediator is mechanistically involved in the pathogenesis of TMJ
      OA. Compared to basal expression in control TMJs, the positive co-localized
      staining for Tgf-beta1, HtrA1, and p-Smad2 in both mutants demonstrates
      involvement of these molecules in the degradative pathway of OA. Tgf-beta1
      therefore is a potential target for further study for the diagnosis and treatment
      of TMJ OA.

PMID- 27031307
TI  - Malignant transformation in non-recurrent peritoneal cystic mesothelioma Our
      experience and review of the literature.
AB  - AIM: Cystic peritoneal mesothelioma is commonly regarded as a benign neoplasm at
      its first manifestation. It can only seldom show malignant transformation, and
      only after repeated postoperative recurrences. MATERIAL OF STUDY: We hereby
      represent a unique case of peritoneal cystic mesothelioma, malignant since its
      first presentation. We observed a 73 year-old man presenting with intermittent
      abdominal pain and periumbilical swelling. At surgery, we found an extensive,
      oval-shaped, multi-lobed cystic formation that was surgically removed. RESULTS:
      Histopathology was consistent with a malignant peritoneal cystic mesothelioma. In
      agreement with oncologists, we decided not to give any further therapy because of
      the few possibilities offered by systemic chemotherapy and the paucity of
      published data from the literature. We planned periodical follow-up including US
      scan every six and CTscan every 12 months. DISCUSSION: Several cases of malignant
      transformation occurring after repeated recurrences of peritoneal mesothelioma
      have been reported. To our knowledge, this is the first case showing "ab initio"
      histological features of malignancy, typical of an active, proliferating and
      infiltrating lesion. In addition, advanced age and male gender of our patient are
      extremely peculiar CONCLUSION: Our observation suggests the possibility, although
      very rare, that peritoneal cystic mesothelioma may present as malignant since its
      first manifestation. KEY WORDS: Peritoneal cystic mesothelioma.

PMID- 27031308
TI  - Erratum: Vol. 65, No. 10.
AB  - In the report, "Human Rabies - Missouri, 2014," on page 255, the second sentence
      of the first full paragraph should read as follows: "The rabies variant
      associated with this bat species occasionally infects other bats (e.g., Tadarida
      braziliensis [Mexican free-tailed bat]) as well as cats, foxes, and other
      species." 

PMID- 27031309
TI  - Complementary and Alternative Medicine in Autism: The Question of Omega-3.
AB  - The use of complementary and alternative medicine is widespread among children
      with autism spectrum disorder (ASD), but methodologically rigorous studies are
      still necessary to establish its effects. In this article, we address the role of
      omega-3 in the treatment of ASD, reviewing the relevant literature highlighted by
      searches of PubMed from 1949 to the present. According to the criteria of
      evidence-based medicine (ie, randomized clinical trials), the data do not support
      the effectiveness of omega-3 treatment in children with ASD. However, based on
      anecdotal experiences and on nonrandomized trials, we cannot exclude that there
      might be a subset of people with ASD who do respond to this type of approach. We
      propose a series of questions to be answered by future studies to clarify the
      possible role of omega-3 in the treatment of ASD.

PMID- 27031310
TI  - Swan Song.

PMID- 27031311
TI  - Adolescent Concussion and Return-to-Learn.
AB  - Concussion is a common diagnosis in adolescents, particularly in those who play
      sports. Physical and cognitive rest is the mainstay of treatment. However, the
      guidelines for returning to full cognitive effort are more nebulous. This article
      examines the existing evidence on return-to-learn guidelines, and offers some
      ideas of school accommodations that can be made for students who have experienced
      a concussion. This article also reviews the situations in which it is recommended
      to seek guidance from a concussion specialist or sports medicine physician.

PMID- 27031312
TI  - An Unusual Cause of Vaginal Bleeding in a Prepubertal Girl.

PMID- 27031313
TI  - A 16-Year-Old Boy with a Rare Respiratory Papillomatosis Complication.

PMID- 27031314
TI  - Youth Athletes and Sports Medicine: Part 2.

PMID- 27031315
TI  - Anticipatory Guidance for Long-Distance Running in Young Athletes.
AB  - More young children are participating in endurance running events such as full
      and half marathons, and the safety of these events for children has been heavily
      debated. There is a paucity of evidence on either side of the debate. However,
      overuse injuries, stress fractures, as well as the potential for psychologic
      burnout are legitimate concerns. Parents who are seeking advice from
      pediatricians about child participation in these endurance events should be made
      aware of these risks. Young children may participate in endurance running events
      under close supervision from health professionals, coaches, and parents, with
      full medical evaluation before initiation of training, throughout training, as
      well as 6 to 12 months post-race. Special attention should be made to the
      psychologic well-being of the child, with the participation in running being
      child-driven, not parent- or coach-driven, and emphasis on enjoyment and fitness,
      not competition.

PMID- 27031316
TI  - Weight Management Counseling for Wrestling Athletes.
AB  - Helping a wrestler manage body weight can be a daunting process for a pediatric
      health care provider. Each high school wrestling program has been mandated by the
      National Federation of State High School Associations to determine an appropriate
      weight classification for each individual wrestler. This article discusses how an
      appropriate weight class is determined, the methods for ascertaining a person's
      hydration status and body density, and the importance of a fully hydrated and
      normally nourished state that will allow for optimal athletic performance for a
      wrestler.

PMID- 27031317
TI  - Approach to the Underperforming Athlete.
AB  - Children and adolescents who participate in intense sports training may face
      physical and psychologic stresses. The pediatric health care provider can play an
      important role in monitoring an athlete's preparation by obtaining a proper
      sports history, assessing sleep hygiene, discussing nutrition and hydration
      guidelines, and evaluating physiologic causes of fatigue. Educating parents and
      athletes on the potential risks of high-intensity training, inadequate rest and
      sleep, and a poor diet may improve the athlete's performance and prevent symptoms
      of overtraining syndrome. Infectious mononucleosis must also be considered a
      cause of fatigue among adolescents. The signs and symptoms of overtraining and
      burnout are discussed in this article.

PMID- 27031318
TI  - Amenorrhea in the Female Athlete: What to Do and When to Worry.
AB  - Functional hypothalamic amenorrhea is a diagnosis of exclusion that is common in
      female athletes, particularly those participating in aesthetic sports (ballet,
      other dance genres, figure skating, and gymnastics) and endurance sports (cross
      country running). Although common, it should be considered abnormal even in the
      high-level elite athlete. Amenorrhea in combination with low energy availability
      and low bone density is labeled "the Female Athlete Triad." Studies have
      demonstrated numerous long-term consequences of athletes suffering from all or a
      portion of this triad, including increased rate of musculoskeletal injuries,
      stress fractures, abnormal lipid profiles, endothelial dysfunction, potential
      irreversible bone loss, depression, anxiety, low self- esteem, and increased
      mortality. This article provides the clinician with the tools to evaluate an
      athlete with secondary amenorrhea, reviews the recommended treatment options for
      affected athletes, and discusses when to return to the activity in an effort to
      facilitate "healthy" participation.

PMID- 27031319
TI  - The association between interdelivery interval and adverse perinatal outcomes in
      a diverse US population.
AB  - OBJECTIVE: The objective of this study was to investigate the association between
      interdelivery interval (IDI) and subsequent perinatal outcomes in a large
      population-based cohort. STUDY DESIGN: Retrospective cohort study of primiparous
      women with singleton gestations giving birth in the US in 2011 to 2012. IDI was
      defined as the time between last live birth and index live birth. IDI was
      categorized as 4 to 17 months, 18 to 36 months (referent), 37 to 60 months and
      >60 months. Statistical comparisons were made using chi-square tests and
      multivariable logistic regression models to control for confounding. Covariates
      included maternal age, prior preterm birth, prior cesarean and medical
      comorbidities. RESULTS: Of the 1 964 523 women meeting study criteria, 9.0% had
      an IDI of 4 to 17 months, 39.7% 18 to 36 months, 26.8% 37 to 60 months and 24.5%
      >60 months. Short IDI was associated with preterm delivery (<37 weeks; 13.8 vs
      8.8%, (adjusted odds ratio (aOR) 1.51, 95% confidence interval (CI) 1.48 to
      1.53)) and adverse perinatal outcomes including low 5-min Apgar, small for
      gestational age (SGA) status and neonatal intensive care unit (NICU) admission.
      Women with long IDI had a higher risk of induction of labor, cesarean delivery,
      chorioamnionitis, maternal ICU admission, preterm delivery and SGA status, 5-min
      Apgar score <4, and NICU admission. CONCLUSIONS: Compared with women with 18 to
      36 month IDIs, women with either shorter or very long IDIs were at an increased
      risk of adverse maternal and neonatal outcomes.

PMID- 27031320
TI  - Inhaled nitric oxide use in preterm infants in California neonatal intensive care
      units.
AB  - OBJECTIVE: To describe inhaled nitric oxide (iNO) exposure in preterm infants and
      variation in neonatal intensive care unit (NICU) use. STUDY DESIGN: This was a
      retrospective cohort study of infants, 22 to 33+6/7 weeks of gestational age
      (GA), during 2005 to 2013. Analyses were stratified by GA and included population
      characteristics, iNO use over time and hospital variation. RESULTS: Of the 65 824
      infants, 1718 (2.61%) received iNO. Infants, 22 to 24+6/7 weeks of GA, had the
      highest incidence of iNO exposure (6.54%). Community NICUs (n=77, median hospital
      use rate 0.7%) used less iNO than regional NICUs (n=23, median hospital use rate
      5.8%). In 22 to 24+6/7 weeks of GA infants, the median rate in regional centers
      was 10.6% (hospital interquartile range 3.8% to 22.6%). CONCLUSION: iNO exposure
      varied with GA and hospital level, with the most use in extremely premature
      infants and regional centers. Variation reflects a lack of consensus regarding
      the appropriate use of iNO for preterm infants.

PMID- 27031321
TI  - Post-event debriefings during neonatal care: why are we not doing them, and how
      can we start?
AB  - Post-event debriefings are a foundational behavior of high performing teams.
      Despite the inherent value of post-event debriefings, the frequency with which
      they are used in neonatal care is extremely low. If post-event debriefings are so
      beneficial, why aren't they conducted more frequently? The reasons are many, but
      solutions are available. In this report, we provide practical advice on
      conducting post-event debriefing in neonatal care. In addition, we examine the
      perceived barriers to conducting post-event debriefings, and offer strategies to
      overcome them. Finally, we consider opportunities to foster a culture change
      within neonatal care which integrates debriefing as standard daily work. By
      establishing a safety culture in neonatal care that encourages and facilitates
      effective post-event debriefings, patient safety can be enhanced and clinical
      outcomes can be improved.

PMID- 27031322
TI  - The effect of glucose administration on perceived fetal movements in women with
      decreased fetal movement, a double-blinded placebo-controlled trial.
AB  - OBJECTIVE: To assess the effect of maternal glucose administration on perceived
      fetal movements. STUDY DESIGN: This was a randomized, double-blinded placebo
      controlled trial. Patients 28-41 weeks singleton gestation complaining of
      decreased fetal movements (DFM) were assigned to receive either 500 cc dextrose
      5% (group A) or 500 cc normal saline (group B) intravenously. Primary outcome was
      number of fetal movements recorded during the following 30 min. Secondary
      outcomes included need for admission or induction of labor owing to persistent
      DFM. Maternal glucose levels were taken before and after intervention. A sample
      size of 50 patients was planned in order to detect a 30% increase in fetal
      movements in group A. RESULTS: Between February 2011 and April 2013, 50 patients
      were recruited. Demographic characteristics were similar among groups. There was
      no difference in the number of fetal movements recorded (7+/-6 vs 8.8+/-6
      movements/30 min, group A and B, respectively, P=0.39). Similar number of
      patients had persistent DFM that required admission (8 vs 10 patients, P=0.77, OR
      1.4, confidence interval (CI) 0.38-5.3); of those admitted, similar number of
      patients had induction of labor (3 vs 6 patients, P=0.64, OR 0.4, CI 0.03-3.8).
      Maternal glucose levels were similar at recruitment (88+/-19 vs 83+/-15 mg dl(-1)
      P=0.36) but were significantly higher in group A (161+/-37 vs 75+/-15 mg dl(-1)
      P<0.0001) after intervention. CONCLUSION: In women with DFM, maternal glucose
      administration has no effect on perceived fetal movement and its clinical use is
      questionable.

PMID- 27031324
TI  - Object selection costs in visual working memory: A diffusion model analysis of
      the focus of attention.
AB  - A central question in working memory research concerns the degree to which
      information in working memory is accessible to other cognitive processes (e.g.,
      decision-making). Theories assuming that the focus of attention can only store a
      single object at a time require the focus to orient to a target representation
      before further processing can occur. The need to orient the focus of attention
      implies that single-object accounts typically predict response time costs
      associated with object selection even when working memory is not full (i.e.,
      memory load is less than 4 items). For other theories that assume storage of
      multiple items in the focus of attention, predictions depend on specific
      assumptions about the way resources are allocated among items held in the focus,
      and how this affects the time course of retrieval of items from the focus. These
      broad theoretical accounts have been difficult to distinguish because
      conventional analyses fail to separate components of empirical response times
      related to decision-making from components related to selection and retrieval
      processes associated with accessing information in working memory. To better
      distinguish these response time components from one another, we analyze data from
      a probed visual working memory task using extensions of the diffusion decision
      model. Analysis of model parameters revealed that increases in memory load
      resulted in (a) reductions in the quality of the underlying stimulus
      representations in a manner consistent with a sample size model of visual working
      memory capacity and (b) systematic increases in the time needed to selectively
      access a probed representation in memory. The results are consistent with single
      object theories of the focus of attention. The results are also consistent with a
      subset of theories that assume a multiobject focus of attention in which resource
      allocation diminishes both the quality and accessibility of the underlying
      representations. (PsycINFO Database Record

PMID- 27031323
TI  - Cardiac time intervals derived by magnetocardiography in fetuses exposed to
      pregnancy hypertension syndromes.
AB  - OBJECTIVE: To test the hypothesis that fetuses exposed to maternal preeclampsia
      or chronic hypertension have deranged development of cardiac time intervals.
      STUDY DESIGN: Pregnancies were divided into three groups: Intrauterine Growth
      Restricted (IUGR), Hypertensive, and Normal. Each group's mean fetal cardiac time
      intervals (P, PR, QRS and RR) derived by magnetocardiography were calculated
      using an analysis of covariance model's regression-adjusted estimates for a
      gestational age of 35 weeks. RESULTS: We reviewed 141 recordings from 21 IUGR, 46
      Hypertensive and 74 Normal patients. The IUGR, Hypertensive and Normal groups,
      respectively, had adjusted mean intervals in milliseconds of 66.4, 66.8 and 76.2
      for P (P=0.001), 95.9, 101.6 and 109.6 for PR (P=0.002), 77.2, 78.7 and 78.7 for
      QRS (P=0.81) and 429.8, 429.2 and 428.5 for RR (P=0.97). CONCLUSION: P and PR
      intervals are abbreviated in normotrophic fetuses exposed to maternal
      hypertension, suggesting shortened atrioventricular conduction times.

PMID- 27031325
TI  - Incidental learning of trust: Examining the role of emotion and visuomotor
      fluency.
AB  - Eye gaze is a powerful directional cue that automatically evokes joint attention
      states. Even when faces are ignored, there is incidental learning of the
      reliability of the gaze cueing of another person, such that people who look away
      from targets are judged less trustworthy. In a series of experiments, we
      demonstrated further properties of the incidental learning of trust from gaze
      direction. First, the emotion of the face, whether neutral or smiling, influenced
      the pattern of trust learning. Second, the effect was specific to judgments of
      trust; reliability of gaze direction did not influence other emotional judgments
      of a person, such as liking. And third, visuomotor fluency was not sufficient for
      learning of trust, whether or not the face served as a target or as a distractor.
      Taken together, incidental learning of trust is influenced by facial emotion, it
      is a specific effect that does not generalize to other emotional assessments, and
      it is not determined solely by processing fluency. (PsycINFO Database Record

PMID- 27031326
TI  - Responsive management of early resistance in cognitive-behavioral therapy for
      generalized anxiety disorder.
AB  - OBJECTIVE: Client resistance limits the efficacy of cognitive-behavioral therapy
      (CBT), rendering it an important process marker for clinicians. Yet, little is
      known about how CBT therapists' responsively navigate resistance. This study
      examined whether differences in therapists' behavior during moments of early
      resistance in CBT predict distal (posttreatment worry) and proximal (subsequent
      resistance) therapy outcomes. We hypothesized that clinicians' use of supportive,
      motivational interviewing (MI)-consistent strategies versus directive CBT methods
      during resistance episodes would relate to more favorable outcomes. METHOD:
      Clients (N = 30) with severe generalized anxiety disorder (GAD) were treated with
      CBT (without MI) in the context of a randomized controlled trial. An adapted
      version of the Client Resistance Code was used to identify moments of client
      disagreement with therapist direction, and these episodes were rated for
      therapist behavior using the Motivational Interviewing Treatment Integrity
      (MITI). Context-specific variations in therapists' MITI ratings during
      disagreement were compared with variations in ratings during randomly selected
      moments to examine whether the timing of therapist use of theoretically indicated
      MI skills differentially impacted outcomes. RESULTS: Clients whose therapists
      displayed greater MI-consistent responses during disagreement had lower levels of
      posttreatment worry, t = -2.84, p = .009, and subsequent resistance, t = -2.96, p
      = .013. Additionally, MI-consistent behavior during disagreement was
      substantially related to treatment outcomes, but MI-like behavior during randomly
      selected therapy segments was not (t = -.15, p = .886 for posttreatment worry,
      and t = -.09, p = .934 for subsequent resistance). CONCLUSIONS: Findings support
      the importance of context-responsivity to resistance markers, suggesting that
      systematic incorporation of MI for managing resistance holds promise for
      improving CBT for GAD. (PsycINFO Database Record

PMID- 27031327
TI  - Synthesis of polymers and nanoparticles bearing polystyrene sulfonate brushes for
      chemokine binding.
AB  - The movement of leukocytes to the site of inflammation in response to injury or
      infection is orchestrated by chemokines binding and signaling through cognate
      receptors. The interaction between sulfated tyrosine residues on the flexible N
      terminal tail of the receptor with positively charged regions of the chemokine is
      one of the key recognition features that facilitates binding. In this manuscript
      we describe the synthesis of polymers and silica nanoparticles bearing
      polystyrene sulfonate brushes to mimic the sulfated tyrosine residues. We show
      that both the polymers and nanoparticles possess high binding affinity for the
      chemokine monocyte chemoattractant protein-1 (MCP-1) in monomeric and dimeric
      form. We also demonstrate key differences in the relative affinity for the
      chemokine for the free polymer versus the polymer-derived nanoparticle system. 

PMID- 27031328
TI  - Rethinking Coal: Thin Films of Solution Processed Natural Carbon Nanoparticles
      for Electronic Devices.
AB  - Disordered carbon materials, both amorphous and with long-range order, have been
      used in a variety of applications, from conductive additives and contact
      materials to transistors and photovoltaics. Here we show a flexible solution
      based method of preparing thin films with tunable electrical properties from
      suspensions of ball-milled coals following centrifugation. The as-prepared films
      retain the rich carbon chemistry of the starting coals with conductivities
      ranging over orders of magnitude, and thermal treatment of the resulting films
      further tunes the electrical conductivity in excess of 7 orders of magnitude.
      Optical absorption measurements demonstrate tunable optical gaps from 0 to 1.8
      eV. Through low-temperature conductivity measurements and Raman spectroscopy, we
      demonstrate that variable range hopping controls the electrical properties in as
      prepared and thermally treated films and that annealing increases the sp(2)
      content, localization length, and disorder. The measured hopping energies
      demonstrate electronic properties similar to amorphous carbon materials and
      reduced graphene oxide. Finally, Joule heating devices were fabricated from coal
      based films, and temperatures as high as 285  degrees C with excellent stability
      were achieved.

PMID- 27031329
TI  - Healing by Secondary Intention-Reply.

PMID- 27031330
TI  - Patient Preferences for Receiving Education on Venous Thromboembolism Prevention 
      A Survey of Stakeholder Organizations.
AB  - IMPORTANCE: Venous thromboembolism (VTE) is a major cause of morbidity and
      mortality among hospitalized patients and is largely preventable. Strategies to
      decrease the burden of VTE have focused on improving clinicians' prescribing of
      prophylaxis with relatively less emphasis on patient education. OBJECTIVE: To
      develop a patient-centered approach to education of patients and their families
      on VTE: including importance, risk factors, and benefit/harm of VTE prophylaxis
      in hospital settings. DESIGN, SETTING AND PARTICIPANTS: The objective of this
      study was to develop a patient-centered approach to education of patients and
      their families on VTE: including importance, risk factors, and benefit/harm of
      VTE prophylaxis in hospital settings. We implemented a three-phase, web-based
      survey (SurveyMonkey) between March 2014 and September 2014 and analyzed survey
      data using descriptive statistics. Four hundred twenty one members of several
      national stakeholder organizations and a single local patient and family advisory
      board were invited to participate via email. We assessed participants'
      preferences for VTE education topics and methods of delivery. Participants wanted
      to learn about VTE symptoms, risk factors, prevention, and complications in a
      context that emphasized harm. Although participants were willing to learn using a
      variety of methods, most preferred to receive education in the context of a
      doctor-patient encounter. The next most common preferences were for video and
      paper educational materials. CONCLUSIONS: Patients want to learn about the harm
      associated with VTE through a variety of methods. Efforts to improve VTE
      prophylaxis and decrease preventable harm from VTE should target the entire
      continuum of care and a variety of stakeholders including patients and their
      families.

PMID- 27031331
TI  - Identification of Multiple Stress Responsive Genes by Sequencing a Normalized
      cDNA Library from Sea-Land Cotton (Gossypium barbadense L.).
AB  - BACKGROUND: Plants often face multiple stresses including drought, extreme
      temperature, salinity, nutrition deficiency and biotic stresses during growth and
      development. All the stresses result in a series of physiological and metabolic
      reactions and then generate reversible inhibition of metabolism and growth and
      can cause seriously irreversible damage, even death. At each stage of cotton
      growth, environmental stress conditions pose devastating threats to plant growth
      and development, especially yield and quality. Due to the complex stress
      conditions and unclear molecular mechanisms of stress response, there is an
      urgent need to explore the mechanisms of cotton response against abiotic
      stresses. METHODOLOGY AND PRINCIPAL FINDINGS: A normalized cDNA library was
      constructed using Gossypium barbadense Hai-7124 treated with different stress
      conditions (heat, cold, salt, drought, potassium and phosphorus deficit and
      Verticillium dahliae infection). Random sequencing of this library generated
      6,047 high-quality expressed sequence tags (ESTs). The ESTs were clustered and
      assembled into 3,135 uniESTs, composed of 2,497 contigs and 638 singletons. The
      blastx results demonstrated 2,746 unigenes showing significant similarity to
      known genes, 74 uniESTs displaying significant similarity to genes of predicted
      proteins, and 315 uniESTs remain uncharacterized. Functional classification
      unveiled the abundance of uniESTs in binding, catalytic activity, and structural
      molecule activity. Annotations of the uniESTs by the plant transcription factor
      database (PlantTFDB) and Plant Stress Protein Database (PSPDB) disclosed that
      transcription factors and stress-related genes were enriched in the current
      library. The expression of some transcription factors and specific stress-related
      genes were verified by RT-PCR under various stress conditions.
      CONCLUSIONS/SIGNIFICANCE: Annotation results showed that a huge number of genes
      respond to stress in our study, such as MYB-related, C2H2, FAR1, bHLH, bZIP,
      MADS, and mTERF. These results will improve our knowledge of stress tolerance in
      cotton. In addition, they are also helpful in discovering candidate genes related
      to stress tolerance. The publicly available ESTs from G. barbadense are a
      valuable genomic resource that will facilitate further molecular study and
      breeding of stress-tolerant cotton.

PMID- 27031332
TI  - Cataract Surgery and Age-Related Macular Degeneration in the 2008-2012 Korea
      National Health and Nutrition Examination Survey.
AB  - IMPORTANCE: In the past, concern has been raised that cataract surgery may be
      associated with the incidence or progression of age-related macular degeneration
      (AMD); inconsistent findings from previous studies have puzzled clinicians. In
      addition, data addressing this association in Asian populations and in the era of
      phacoemulsification are scarce. OBJECTIVE: To determine the associations between
      cataract surgery and AMD in a representative Korean population. DESIGN, SETTING,
      AND PARTICIPANTS: This cross-sectional study used a multistage, probability
      cluster survey sample to produce nationally representative estimates. Data were
      analyzed from the Korea National Health and Nutrition Examination Survey
      (KNHANES), which included results for cataract surgery status and AMD grading
      from 2008 to 2012. A total of 20 419 participants 40 years or older were
      included. Data were analyzed from February 5 to August 20, 2015. MAIN OUTCOMES
      AND MEASURES: The association between cataract surgery and AMD was assessed in
      each right and left eye using logistic regression models and in both eyes using
      generalized estimating equation models. Sample weights were applied to adjust for
      survey design, nonresponse, and stratification to generate nationally
      representative population-based results. RESULTS: From the 20 419 eligible
      individuals (11 642 women [51.9%] and 5777 men [48.1%]; mean [SE] age, 55.83
      [0.14] years), 17 987 had information regarding cataract surgery status and
      gradable fundus photographs of at least 1 eye. A total of 34 863 eyes (17 616
      right eyes and 17 247 left eyes) underwent analysis. Of these, 1264 right eyes
      (5.5%) and 1235 left eyes (5.4%) had cataract surgery. Of 1056 right eyes and 949
      left eyes with any AMD (early or late), 167 right eyes (15.2%) and 147 left eyes
      (13.7%) had cataract surgery. The analyses did not show any association between
      cataract surgery and any form of AMD (early, late, and all) except in left eyes,
      where cataract surgery was associated with late AMD (odds ratio, 2.34; 95% CI,
      1.13-4.85). CONCLUSIONS AND RELEVANCE: The results suggest that the association
      between cataract surgery and AMD is uncertain in the current era of
      phacoemulsification. The association for left eyes might be a chance finding.

PMID- 27031333
TI  - The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3) in
      Huntington's Disease Mice.
AB  - An important epigenetic modification in Huntington's disease (HD) research is
      histone acetylation, which is regulated by histone acetyltransferase and histone
      deacetylase (HDAC) enzymes. HDAC inhibitors have proven effective in HD model
      systems, and recent work is now focused on functional dissection of the
      individual HDAC enzymes in these effects. Histone deacetylase 3 (HDAC3), a member
      of the class I subfamily of HDACs, has previously been implicated in neuronal
      toxicity and huntingtin-induced cell death. Hence, we tested the effects of
      RGFP966 ((E)-N-(2-amino-4-fluorophenyl)-3-(1-cinnamyl-1H-pyrazol-4
      yl)acrylamide), a benzamide-type HDAC inhibitor that selectively targets HDAC3,
      in the N171-82Q transgenic mouse model of HD. We found that RGFP966 at doses of
      10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration,
      accompanied by neuroprotective effects on striatal volume. In light of previous
      studies implicating HDAC3 in immune function, we measured gene expression changes
      for 84 immune-related genes elicited by RGFP966 using quantitative PCR arrays.
      RGFP966 treatment did not cause widespread changes in cytokine/chemokine gene
      expression patterns, but did significantly alter the striatal expression of
      macrophage migration inhibitory factor (Mif), a hormone immune modulator
      associated with glial cell activation, in N171-82Q transgenic mice, but not WT
      mice. Accordingly, RGFP966-treated mice showed decreased glial fibrillary acidic
      protein (GFAP) immunoreactivity, a marker of astrocyte activation, in the
      striatum of N171-82Q transgenic mice compared to vehicle-treated mice. These
      findings suggest that the beneficial actions of HDAC3 inhibition could be
      related, in part, with lowered Mif levels and its associated downstream effects. 

PMID- 27031334
TI  - The Goat (Capra hircus) Mammary Gland Mitochondrial Proteome: A Study on the
      Effect of Weight Loss Using Blue-Native PAGE and Two-Dimensional Gel
      Electrophoresis.
AB  - Seasonal weight loss (SWL) is the most important limitation to animal production
      in the Tropical and Mediterranean regions, conditioning producer's incomes and
      the nutritional status of rural communities. It is of importance to produce
      strategies to oppose adverse effects of SWL. Breeds that have evolved in harsh
      climates have acquired tolerance to SWL through selection. Most of the factors
      determining such ability are related to changes in biochemical pathways as
      affected by SWL. In this study, a gel based proteomics strategy (BN: Blue-Native
      Page and 2DE: Two-dimensional gel electrophoresis) was used to characterize the
      mitochondrial proteome of the secretory tissue of the goat mammary gland. In
      addition, we have conducted an investigation of the effects of weight loss in two
      goat breeds with different levels of adaptation to nutritional stress: Majorera
      (tolerant) and Palmera (susceptible). The study used Majorera and Palmera dairy
      goats, divided in 4 sets, 2 for each breed: underfed group fed on wheat straw
      (restricted diet, so their body weight would be 15-20% reduced by the end of
      experiment), and a control group fed with an energy-balanced diet. At the end of
      the experimental period (22 days), mammary gland biopsies were obtained for all
      experimental groups. The proteomic analysis of the mitochondria enabled the
      resolution of a total of 277 proteins, and 148 (53%) were identified by MALDI
      TOF/TOF mass spectrometry. Some of the proteins were identified as subunits of
      the glutamate dehydrogenase complex and the respiratory complexes I, II, IV, V
      from mitochondria, as well as numerous other proteins with functions in:
      metabolism, development, localization, cellular organization and biogenesis,
      biological regulation, response to stimulus, among others, that were mapped in
      both BN and 2DE gels. The comparative proteomics analysis enabled the
      identification of several proteins: NADH-ubiquinone oxidoreductase 75 kDa subunit
      and lamin B1 mitochondrial (up-regulated in the Palmera breed), Guanine
      nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (up-regulated in the
      Majorera breed) and cytochrome b-c1 complex subunit 1, mitochondrial and Chain D,
      Bovine F1-C8 Sub-Complex Of Atp Synthase (down-regulated in the Majorera breed)
      as a consequence of weight loss. 

PMID- 27031335
TI  - Chemotaxis and Binding of Pseudomonas aeruginosa to Scratch-Wounded Human Cystic
      Fibrosis Airway Epithelial Cells.
AB  - Confocal imaging was used to characterize interactions of Pseudomonas aeruginosa
      (PA, expressing GFP or labeled with Syto 11) with CF airway epithelial cells
      (CFBE41o-, grown as confluent monolayers with unknown polarity on coverglasses)
      in control conditions and following scratch wounding. Epithelia and PAO1-GFP or
      PAK-GFP (2 MOI) were incubated with Ringer containing typical extracellular
      salts, pH and glucose and propidium iodide (PI, to identify dead cells). PAO1 and
      PAK swam randomly over and did not bind to nonwounded CFBE41o- cells. PA migrated
      rapidly (began within 20 sec, maximum by 5 mins) and massively (10-80 fold
      increase, termed "swarming"), but transiently (random swimming after 15 mins), to
      wounds, particularly near cells that took up PI. Some PA remained immobilized on
      cells near the wound. PA swam randomly over intact CFBE41o- monolayers and
      wounded monolayers that had been incubated with medium for 1 hr. Expression of
      CFTR and altered pH of the media did not affect PA interactions with CFBE41o-
      wounds. In contrast, PAO1 swarming and immobilization along wounds was abolished
      in PAO1 (PAO1DeltacheYZABW, no expression of chemotaxis regulatory components
      cheY, cheZ, cheA, cheB and cheW) and greatly reduced in PAO1 that did not express
      amino acid receptors pctA, B and C (PAO1DeltapctABC) and in PAO1 incubated in
      Ringer containing a high concentration of mixed amino acids. Non-piliated
      PAKDeltapilA swarmed normally towards wounded areas but bound infrequently to
      CFBE41o- cells. In contrast, both swarming and binding of PA to CFBE41o- cells
      near wounds were prevented in non-flagellated PAKDeltafliC. Data are consistent
      with the idea that (i) PA use amino acid sensor-driven chemotaxis and flagella
      driven swimming to swarm to CF airway epithelial cells near wounds and (ii) PA
      use pili to bind to epithelial cells near wounds. 

PMID- 27031336
TI  - Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in
      a Chromosome-16 Congenic Rat Model.
AB  - Metabolic syndrome is a highly prevalent human disease with substantial genomic
      and environmental components. Previous studies indicate the presence of
      significant genetic determinants of several features of metabolic syndrome on rat
      chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the
      SHR.BN16 congenic strain by introgression of a limited RNO16 region from the
      Brown Norway congenic strain (BN-Lx) into the genomic background of the
      spontaneously hypertensive rat (SHR) strain. We compared the morphometric,
      metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also
      compared in silico the DNA sequences for the differential segment in the BN-Lx
      and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight,
      decreased concentrations of total triglycerides and cholesterol, and improved
      glucose tolerance compared with SHR rats. The concentrations of insulin, free
      fatty acids, and adiponectin were comparable between the two strains. SHR.BN16
      rats had significantly lower systolic (18-28 mmHg difference) and diastolic (10
      15 mmHg difference) blood pressure throughout the experiment (repeated-measures
      ANOVA, P < 0.001). The differential segment spans approximately 22 Mb of the
      telomeric part of the short arm of RNO16. The in silico analyses revealed over
      1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential
      segment, 44 of which lead to missense mutations, and only eight of which (in
      Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes) are
      predicted to be damaging to the protein product. Furthermore, a number of genes
      within the RNO16 differential segment associated with metabolic syndrome
      components in human studies showed polymorphisms between SHR and BN-Lx (including
      Lpl, Nrg3, Pbx4, Cilp2, and Stab1). Our novel congenic rat model demonstrates
      that a limited genomic region on RNO16 in the SHR significantly affects many of
      the features of metabolic syndrome. 

PMID- 27031337
TI  - Genetic Diversity of Intimin Gene of Atypical Enteropathogenic Escherichia coli
      Isolated from Human, Animals and Raw Meats in China.
AB  - Atypical enteropathogenic Escherichia coli (aEPEC) is considered to be an
      emerging enteropathogen that is more prevalent than typical EPEC in developing
      and developed countries. The major adherence factor, intimin, an outer membrane
      protein encoded by eae, plays a pivotal role in the pathogenesis of aEPEC. This
      study investigated the distribution and polymorphisms of intimin subtypes of 143
      aEPEC strains from diarrheal patients, healthy carriers, animals, and raw meats
      in China. These aEPEC strains belonged to more than 71 different serotypes, which
      comprised 52 O serogroups and 24 H types. Sixty-eight different eae genotypes and
      19 intimin subtypes were detected. Eighteen, eight, seven, and five intimin
      subtypes were identified from 86 diarrheal patients, 14 healthy carriers, 19
      animals, and 24 raw meats strains, respectively. Intimin beta1 was the most
      prevalent subtype in strains from diarrheal patients (34.88%) and animals
      (47.37%). There was a statistically significant difference in the distribution of
      eae-beta1 between diarrheal patients and healthy carriers (P = 0.004). Intimin
      theta was more predominant among raw meat strains (50%) than among diarrheal
      patients strains (12.79%, P = 0.0003), healthy carrier strains (7.14%, P =
      0.007), or animal strains (15.79%, P = 0.020). The two predominant subtypes (eae
      beta1 and eae-theta) had considerable polymorphisms with no significant
      differences among the four sources. PFGE analysis revealed 119 distinct patterns
      and the strains were clustered into 11 groups with similarity indices ranging
      from 63% to 100%. These results suggest that in China, aEPEC strains from
      different sources are highly heterogeneous. Animals and raw meats are important
      sources of genetically diverse intimin-harboring aEPEC, which might serve as
      important transmission vehicles of these bacteria. 

PMID- 27031338
TI  - Evolutionary and Biogeographic Insights on the Macaronesian Beta-Patellifolia
      Species (Amaranthaceae) from a Time-Scaled Molecular Phylogeny.
AB  - The Western Mediterranean Region and Macaronesian Islands are one of the top
      biodiversity hotspots of Europe, containing a significant native genetic
      diversity of global value among the Crop Wild Relatives (CWR). Sugar beet is the
      primary crop of the genus Beta (subfamily Betoideae, Amaranthaceae) and despite
      the great economic importance of this genus, and of the close relative
      Patellifolia species, a reconstruction of their evolutionary history is still
      lacking. We analyzed nrDNA (ITS) and cpDNA gene (matK, trnH-psbA, trnL intron,
      rbcL) sequences to: (i) investigate the phylogenetic relationships within the
      Betoideae subfamily, and (ii) elucidate the historical biogeography of wild beet
      species in the Western Mediterranean Region, including the Macaronesian Islands.
      The results support the Betoideae as a monophyletic group (excluding the
      Acroglochin genus) and provide a detailed inference of relationships within this
      subfamily, revealing: (i) a deep genetic differentiation between Beta and
      Patellifolia species, which may have occurred in Late Oligocene; and (ii) the
      occurrence of a West-East genetic divergence within Beta, indicating that the
      Mediterranean species probably differentiated by the end of the Miocene. This was
      interpreted as a signature of species radiation induced by dramatic habitat
      changes during the Messinian Salinity Crisis (MSC, 5.96-5.33 Mya). Moreover,
      colonization events during the Pleistocene also played a role in shaping the
      current diversity patterns among and within the Macaronesian Islands. The origin
      and number of these events could not be revealed due to insufficient phylogenetic
      resolution, suggesting that the diversification was quite recent in these
      archipelagos, and unravelling potential complex biogeographic patterns with
      hybridization and gene flow playing an important role. Finally, three
      evolutionary lineages were identified corresponding to major gene pools of sugar
      beet wild relatives, which provide useful information for establishing in situ
      and ex situ conservation priorities in the hotspot area of the Macaronesian
      Islands. 

PMID- 27031339
TI  - Assessment of Micro-Basin Tillage as a Soil and Water Conservation Practice in
      the Black Soil Region of Northeast China.
AB  - Micro-basin tillage is a soil and water conservation practice that requires
      building individual earth blocks along furrows. In this study, plot experiments
      were conducted to assess the efficiency of micro-basin tillage on sloping
      croplands between 2012 and 2013 (5 degrees and 7 degrees ). The conceptual,
      optimal, block interval model was used to design micro-basins which are meant to
      capture the maximum amount of water per unit area. Results indicated that when
      compared to the up-down slope tillage, micro-basin tillage could increase soil
      water content and maize yield by about 45% and 17%, and reduce runoff, sediment
      and nutrients loads by about 63%, 96% and 86%, respectively. Meanwhile, micro
      basin tillage could reduce the peak runoff rates and delay the initial runoff
      yielding time. In addition, micro-basin tillage with the optimal block interval
      proved to be the best one among all treatments with different intervals. Compared
      with treatments of other block intervals, the optimal block interval treatments
      increased soil moisture by around 10% and reduced runoff rate by around 15%. In
      general, micro-basin tillage with optimal block interval represents an effective
      soil and water conservation practice for sloping farmland of the black soil
      region. 

PMID- 27031340
TI  - Single Positive Lymph Node Prostate Cancer Can Be Treated Surgically without
      Recurrence.
AB  - PURPOSE/OBJECTIVES: To investigate pN1 prostate cancer (PCa) patients treated
      surgically without immediate adjuvant treatment. MATERIALS AND METHODS: We
      analyzed the database of 2316 patients at our institution who underwent robot
      assisted radical prostatectomy (RARP)/radical prostatectomy (RP) between July
      2005 and November 2012. 87 patients with pN1 PCa and received no neoadjuvant and
      immediate adjuvant therapy were included in the study. Included pN1 PCa patients
      were followed up for median of 60 months. Biochemical recurrence (BCR)-free
      survival, metastasis-free survival (MFS), cancer specific survival (CSS), and
      overall survival (OS) rates were determined by using Kaplan-Meier analysis. Cox
      regression analysis was performed to investigate the impact of prostate-specific
      antigen (PSA) level, Gleason score, extraprostatic extension, seminal vesicle
      invasion, perineural invasion, lymphovascular invasion, positive surgical margin,
      tumor volume, early post-operative PSA(6 weeks), PSA nadir, lymph node yield, and
      number of pathologically positive lymph nodes on survival. RESULTS: The 5-year OS
      rate of patients was 86.1%, while the CSS rate was 89.6%. The metastasis-free and
      BCR-free survival rates were 71% and 19.1%, respectively, and each was
      significantly correlated with the number of positive lymph nodes on log rank
      tests (p = 0.004 and p = 0.039, respectively). The presence of 2 or more
      pathologically positive LNs (HR:2.20; 95% CI 1.30-3.72; p = 0.003) and a Gleason
      score >=8 (HR: 2.40;95% CI: 1.32-4.38; p = 0.04) were significant negative
      predictors of BCR free survival on multivariable regression analysis.
      Furthermore, the presence of 2 or more positive lymph nodes (HR: 1.06; 95% CI
      1.01-1.11; p = 0.029) were significant negative predictors of metastasis-free
      survival on multivariable regression analysis. Additionally, in the patients who
      had no BCR without adjuvant treatment 9 patients out of 10 (90%) had single
      positive LN and 5 patients out of 10 (50%) had Gleason score 7. Therefore, single
      positive LN, and Gleason scores <=7 have significantly low risk of disease
      progression. CONCLUSIONS: pN1 PCa patients have heterogenous clinical courses.
      Patients with single positive LN, and Gleason scores <=7 have low risk of
      recurrence. Close observation with delayed adjuvant hormone therapy can be
      considered in these patients.

PMID- 27031341
TI  - Involvement of Alternative Splicing in Barley Seed Germination.
AB  - Seed germination activates many new biological processes including DNA, membrane
      and mitochondrial repairs and requires active protein synthesis and sufficient
      energy supply. Alternative splicing (AS) regulates many cellular processes
      including cell differentiation and environmental adaptations. However, limited
      information is available on the regulation of seed germination at post
      transcriptional levels. We have conducted RNA-sequencing experiments to dissect
      AS events in barley seed germination. We identified between 552 and 669 common AS
      transcripts in germinating barley embryos from four barley varieties (Hordeum
      vulgare L. Bass, Baudin, Harrington and Stirling). Alternative 3' splicing (34%
      45%), intron retention (32%-34%) and alternative 5' splicing (16%-21%) were three
      major AS events in germinating embryos. The AS transcripts were predominantly
      mapped onto ribosome, RNA transport machineries, spliceosome, plant hormone
      signal transduction, glycolysis, sugar and carbon metabolism pathways.
      Transcripts of these genes were also very abundant in the early stage of seed
      germination. Correlation analysis of gene expression showed that AS hormone
      responsive transcripts could also be co-expressed with genes responsible for
      protein biosynthesis and sugar metabolisms. Our RNA-sequencing data revealed that
      AS could play important roles in barley seed germination. 

PMID- 27031342
TI  - The South China Sea and Its Neglected Tropical Diseases.

PMID- 27031343
TI  - Audio-Visual and Meaningful Semantic Context Enhancements in Older and Younger
      Adults.
AB  - Speech perception is critical to everyday life. Oftentimes noise can degrade a
      speech signal; however, because of the cues available to the listener, such as
      visual and semantic cues, noise rarely prevents conversations from continuing.
      The interaction of visual and semantic cues in aiding speech perception has been
      studied in young adults, but the extent to which these two cues interact for
      older adults has not been studied. To investigate the effect of visual and
      semantic cues on speech perception in older and younger adults, we recruited
      forty-five young adults (ages 18-35) and thirty-three older adults (ages 60-90)
      to participate in a speech perception task. Participants were presented with
      semantically meaningful and anomalous sentences in audio-only and audio-visual
      conditions. We hypothesized that young adults would outperform older adults
      across SNRs, modalities, and semantic contexts. In addition, we hypothesized that
      both young and older adults would receive a greater benefit from a semantically
      meaningful context in the audio-visual relative to audio-only modality. We
      predicted that young adults would receive greater visual benefit in semantically
      meaningful contexts relative to anomalous contexts. However, we predicted that
      older adults could receive a greater visual benefit in either semantically
      meaningful or anomalous contexts. Results suggested that in the most supportive
      context, that is, semantically meaningful sentences presented in the audiovisual
      modality, older adults performed similarly to young adults. In addition, both
      groups received the same amount of visual and meaningful benefit. Lastly, across
      groups, a semantically meaningful context provided more benefit in the audio
      visual modality relative to the audio-only modality, and the presence of visual
      cues provided more benefit in semantically meaningful contexts relative to
      anomalous contexts. These results suggest that older adults can perceive speech
      as well as younger adults when both semantic and visual cues are available to the
      listener. 

PMID- 27031345
TI  - Triggering the Mechanical Release of Mineralized Pickering Emulsion-Based
      Capsules.
AB  - Taking advantage of the benefit of Pickering-based emulsions and sol-gel
      chemistry, we synthesized mineralized Pickering emulsion-based capsules
      constituted of a dodecane core and a siliceous shell. To trigger the oily core
      mechanical release, we first made use of the one-step polycondensation synthesis
      path, reaching limited shell thickness from 43 to 115 nm with a resistance
      against the application of an external pressure from 0.5 to 6 MPa. When
      addressing a sequential mineralization route, we were able to reach both better
      shell homogeneity and higher values of shell thickness from 85 to 135 nm
      associated with a shell breaking pressure varying from 1.2 to 10 MPa. In this
      last configuration, the shell homogeneity and thickness are acting cooperatively
      toward enhancing the shell mechanical toughness and the associated effective
      breaking pressure of the dodecane@SiO2 core-shell particles.

PMID- 27031344
TI  - Use of a Chimeric Hsp70 to Enhance the Quality of Recombinant Plasmodium
      falciparum S-Adenosylmethionine Decarboxylase Protein Produced in Escherichia
      coli.
AB  - S-adenosylmethionine decarboxylase (PfAdoMetDC) from Plasmodium falciparum is a
      prospective antimalarial drug target. The production of recombinant PfAdoMetDC
      for biochemical validation as a drug target is important. The production of
      PfAdoMetDC in Escherichia coli has been reported to result in unsatisfactory
      yields and poor quality product. The co-expression of recombinant proteins with
      molecular chaperones has been proposed as one way to improve the production of
      the former in E. coli. E. coli heat shock proteins DnaK, GroEL-GroES and DnaJ
      have previously been used to enhance production of some recombinant proteins.
      However, the outcomes were inconsistent. An Hsp70 chimeric protein, KPf, which is
      made up of the ATPase domain of E. coli DnaK and the substrate binding domain of
      P. falciparum Hsp70 (PfHsp70) has been previously shown to exhibit chaperone
      function when it was expressed in E. coli cells whose resident Hsp70 (DnaK)
      function was impaired. We proposed that because of its domain constitution, KPf
      would most likely be recognised by E. coli Hsp70 co-chaperones. Furthermore,
      because it possesses a substrate binding domain of plasmodial origin, KPf would
      be primed to recognise recombinant PfAdoMetDC expressed in E. coli. First, using
      site-directed mutagenesis, followed by complementation assays, we established
      that KPf with a mutation in the hydrophobic residue located in its substrate
      binding cavity was functionally compromised. We further co-expressed PfAdoMetDC
      with KPf, PfHsp70 and DnaK in E. coli cells either in the absence or presence of
      over-expressed GroEL-GroES chaperonin. The folded and functional status of the
      produced PfAdoMetDC was assessed using limited proteolysis and enzyme assays.
      PfAdoMetDC co-expressed with KPf and PfHsp70 exhibited improved activity compared
      to protein co-expressed with over-expressed DnaK. Our findings suggest that
      chimeric KPf may be an ideal Hsp70 co-expression partner for the production of
      recombinant plasmodial proteins in E. coli. 

PMID- 27031346
TI  - Correction: Naturally-Acquired Immune Response against Plasmodium vivax Rhoptry
      Associated Membrane Antigen.

PMID- 27031347
TI  - Improvement in Oral Diabetes Medication Adherence after a Comprehensive Wellness
      Assessment in a Dual Eligible Population.
AB  - Medication adherence is often lower among disadvantaged patients. Drivers of
      medication adherence may include the quality of communications between patient
      and medical caregiver. The research objective is to assess whether an annual
      Comprehensive Wellness Assessment (CWA) is associated with improved medication
      adherence. The CWA targeted primarily dual eligible Special Needs Plan (SNP)
      enrollees in a Medicare Advantage plan. This retrospective panel study used
      administrative claims data and member-month level data for members who were newly
      diagnosed with diabetes in 2010, allowing for up to 5 years of follow-up. The
      intervention of interest is whether the member received a CWA in the past 12
      months. Multivariate regression models were estimated using pooled member-month
      data and a difference-in-difference type approach to assess whether CWA visits
      improve oral diabetes medication (ODM) adherence among SNP enrollees. Twenty-six
      percent of pooled member-month observations are from SNP enrollees. Average
      monthly ODM adherence is 77.5%. Approximately 31% of SNP enrollees had a CWA in
      the last 12 months, compared to 5% of regular enrollees. Regression results show
      SNP enrollees with a CWA on average had higher monthly adherence by 3.9
      percentage points (P < 0.01), and were 7% more likely to meet the threshold of at
      least 80% adherence (P < 0.01). Adherence is even higher for the subsample of
      African American SNP enrollees with CWA. CWA appears to be effective in improving
      ODM adherence among SNP patients. Care models with components like wellness
      assessments that include medication review and education may improve medication
      adherence as well as Medicare Advantage plan star ratings.

PMID- 27031352
TI  - HIV, HBV and HCV Coinfection Prevalence in Iran--A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: worldwide, hepatitis C and B virus infections (HCV and HCV), are the
      two most common coinfections with human immunodeficiency virus (HIV) and has
      become a major threat to the survival of HIV-infected persons. The review aimed
      to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple
      coinfections in different subpopulations in Iran. METHOD: Following PRISMA
      guidelines, we conducted a systematic review and meta-analysis of reports on
      prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in
      Iran. We systematically reviewed the literature to identify eligible studies from
      January 1996 to March 2012 in English or Persian/Farsi databases. We extracted
      the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot
      test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main
      primary outcome. We reported the prevalence of the three infections and
      coinfections as point and 95% confidence intervals. FINDINGS: HIV prevalence
      varied from %0.00 (95% CI: 0.00-0.003) in the general population to %17.25 (95%
      CI: 2.94-31.57) in people who inject drugs (PWID). HBV prevalence ranged from %
      0.00 (95% CI: 0.00-7.87) in health care workers to % 30.9 (95% CI: 27.88-33.92)
      in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00-0.66) in health care
      workers to %51.46 (95% CI: 34.30-68.62) in PWID. The coinfection of HIV/HBV and
      also HIV/HCV in the general population and in health care workers was zero, while
      the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple
      infections (1.25%) in PWID. CONCLUSIONS: We found that PWID are severely and
      disproportionately affected by HIV and the other two infections, HCV and HBV.
      Screenings of such coinfections need to be reinforced to prevent new infections
      and also reduce further transmission in their community and to others.

PMID- 27031353
TI  - Cas9 Functionally Opens Chromatin.
AB  - Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces
      chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin
      opening is sufficient to enable adjacent binding and transcriptional activation
      by the settler transcription factor retinoic acid receptor at previously unbound
      motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding
      chromatin accessibility to alter local transcription factor binding. 

PMID- 27031354
TI  - Intrinsic Subtypes of Primary Breast Cancer--Gene Expression Analysis.
AB  - Intrinsic subtypes based on gene expression have substantially improved the
      understanding of the biological diversity and heterogeneity of breast cancer. The
      efficacy of adjuvant therapies depends on the level of risk for an individual
      patient. Because of this, careful estimation of the level of risk is mandatory.
      In addition to well-established clinicopathological factors, validated gene
      expression signatures are useful especially in estrogen receptor-positive and
      HER2-negative patients. Commercially available gene expression signatures like
      Prosigna, MammaPrint, Oncotype DX, and EndoPredict are recommended by the
      Arbeitsgemeinschaft Gynakologische Onkologie (AGO) for use in selected patients. 

PMID- 27031355
TI  - CLABSI Conversations: Lessons From Peer-to-Peer Assessments to Reduce Central
      Line-Associated Bloodstream Infections.
AB  - A national collaborative helped many hospitals dramatically reduce central line
      associated bloodstream infections (CLABSIs), but some hospitals struggled to
      reduce infection rates. This article describes the development of a peer-to-peer
      assessment process (CLABSI Conversations) and the practical, actionable practices
      we discovered that helped intensive care unit teams achieve a CLABSI rate of less
      than 1 infection per 1000 catheter-days for at least 1 year. CLABSI Conversations
      was designed as a learning-oriented process, in which a team of peers visited
      hospitals to surface barriers to infection prevention and to share best practices
      and insights from successful intensive care units. Common practices led to 10
      recommendations: executive and board leaders communicate the goal of zero CLABSI
      throughout the hospital; senior and unit-level leaders hold themselves
      accountable for CLABSI rates; unit physicians and nurse leaders own the problem;
      clinical leaders and infection preventionists build infection prevention training
      and simulation programs; infection preventionists participate in unit-based
      CLABSI reduction efforts; hospital managers make compliance with best practices
      easy; clinical leaders standardize the hospital's catheter insertion and
      maintenance practices and empower nurses to stop any potentially harmful acts;
      unit leaders and infection preventionists investigate CLABSIs to identify root
      causes; and unit nurses and staff audit catheter maintenance policies and
      practices. 

PMID- 27031356
TI  - Expanding Continuous Quality Improvement Capacity in the Medical Intensive Care
      Unit: Prehealth Volunteers as a Solution.
AB  - Health care delivery systems are challenged to support the increasing demands for
      improving patient safety, satisfaction, and outcomes. Limited resources and
      staffing are common barriers for making significant and sustained improvements.
      At Oregon Health & Science University, the medical intensive care unit (MICU)
      leadership team faced internal capacity limitations for conducting continuous
      quality improvement, specifically for the implementation and evaluation of the
      mobility portion of an evidence-based care bundle. The MICU team successfully
      addressed this capacity challenge using the person power of prehealth volunteers.
      In the first year of the project, 52 trained volunteers executed an evidence
      based mobility intervention for 305 critically ill patients, conducting more than
      200 000 exercise repetitions. The volunteers contributed to real-time evaluation
      of the project, with the collection of approximately 26 950 process measure data
      points. Prehealth volunteers are an untapped resource for effectively expanding
      internal continuous quality improvement capacity in the MICU and beyond. 

PMID- 27031357
TI  - Involvement Drivers: A Study of Nurses and Physicians in Improvement Work.
AB  - This article reports on the involvement of nurses and physicians in improvement
      work, with a special focus on the drivers. The purpose was to describe how the
      nurse and physician groups understand involvement drivers for improvement work
      and to explain the differences in how they understand involvement. The study was
      conducted at 2 Swedish hospitals, and a total of 20 nurses and 10 physicians were
      interviewed. The theoretical framework, developed by an interpretative approach,
      identifies and describes a number of involvement drivers. On clustering the
      drivers into larger involvement factors, the study shows clear differences and
      profiles in terms of the 2 groups' perception and understanding of the
      involvement-drivers. Each group's profile was then analyzed on the basis of
      concept of professional culture. 

PMID- 27031358
TI  - Building Systemwide Improvement Capability: Does an Organization's Strategy for
      Quality Improvement Matter?
AB  - OBJECTIVES: Health care organizations have used different strategies to implement
      quality improvement (QI) programs but with only mixed success in implementing and
      spreading QI organization-wide. This suggests that certain organizational
      strategies may be more successful than others in developing an organization's
      improvement capability. To investigate this, our study examined how the primary
      focus of grant-funded QI efforts relates to (1) key measures of grant success and
      (2) organization-level measures of success in QI and organizational learning.
      METHODS: Using a mixed-methods design, we conducted one-way analyses of variance
      to relate Veterans Affairs administrative survey data to data collected as part
      of a 3.5-year evaluation of 29 health care organization grant recipients. We then
      analyzed qualitative evidence from the evaluation to explain our results.
      RESULTS: We found that hospitals that focused on developing organizational
      infrastructure to support QI implementation compared with those that focused on
      training or conducting projects rated highest (at alpha = .05) on all 4
      evaluation measures of grant success and all 3 systemwide survey measures of QI
      and organizational learning success. CONCLUSIONS: This study adds to the
      literature on developing organizational improvement capability and has practical
      implications for health care leaders. Focusing on either projects or staff
      training in isolation has limited value. Organizations are more likely to achieve
      systemwide transformation of improvement capability if their strategy emphasizes
      developing or strengthening organizational systems, structures, or processes to
      support direct improvement efforts.

PMID- 27031359
TI  - Impact of Patient-Centered Care Innovations on Access to Providers, Ambulatory
      Care Utilization, and Patient Clinical Indicators in the Veterans Health
      Administration.
AB  - BACKGROUND: The Veterans Health Administration piloted patient-centered care
      (PCC) innovations beginning in 2010 to improve patient and provider experience
      and environment in ambulatory care. We use secondary data to look at longitudinal
      trends, evaluate system redesign, and identify areas for further quality
      improvement. METHODS: This was a retrospective, observational study using
      existing secondary data from multiple US Department of Veteran Affairs sources to
      evaluate changes in veteran and facility outcomes associated with PCC innovations
      at 2 innovation and matched comparison sites between FY 2008-2010 (pre-PCC
      innovations) and FY 2011-2012 (post-PCC innovations). Outcomes included access to
      primary care providers (PCPs); primary, specialty, and emergency care use; and
      clinical indicators for chronic disease. RESULTS: Longitudinal trends revealed a
      different story at each site. One site demonstrated better PCP access, decrease
      in emergency and primary care use, increase in specialty care use, and
      improvement in diabetic glucose control. The other site demonstrated a decrease
      in PCP access and primary care use, no change in specialty care use, and an
      increase in diastolic blood pressure in relation to the comparison site.
      CONCLUSION: Secondary data analysis can reveal longitudinal trends associated
      with system changes, thereby informing program evaluation and identifying
      opportunities for quality improvement.

PMID- 27031360
TI  - Advancing Payment Reform at the Community Level.
AB  - BACKGROUND: Multistakeholder alliances-groups of payers, purchasers, providers,
      and consumers that voluntarily work together to address local health goals-have
      increasingly been used to improve health care quality within their communities.
      Under the Robert Wood Johnson Foundation's Aligning Forces for Quality (AF4Q)
      initiative, 16 multistakeholder alliances were charged with advancing payment
      reform as part of a larger effort to achieve dramatic and sustainable quality
      improvement. METHODS: Drawing upon key informant interviews with alliance leaders
      and document reviews conducted from 2010 to 2014, we describe the payment reform
      projects undertaken by the AF4Q alliances and the roles that the alliances played
      to advance them. RESULTS: The most common types of projects pursued by alliances
      were those that introduced supplemental payments to fee-for-service reimbursement
      and built upon alliances' ongoing quality improvement initiatives. Alliances
      advanced payment reform through 4 roles: (1) educating and advocating, (2)
      designing payment reform projects, (3) recruiting participants, and (4)
      supporting the operation of projects. However, less than half of alliances'
      payment reform projects were operational by 2014. CONCLUSIONS: Quality
      improvement-focused multistakeholder alliances may play meaningful roles to
      advance payment reform, but they are not a panacea for overcoming well-documented
      barriers to reform.

PMID- 27031364
TI  - Direct Fabrication of Monodisperse Silica Nanorings from Hollow Spheres - A
      Template for Core-Shell Nanorings.
AB  - We report a new type of nanosphere colloidal lithography to directly fabricate
      monodisperse silica (SiO2) nanorings by means of reactive ion etching of hollow
      SiO2 spheres. Detailed TEM, SEM, and AFM structural analysis is complemented by a
      model describing the geometrical transition from hollow sphere to ring during the
      etching process. The resulting silica nanorings can be readily redispersed in
      solution and subsequently serve as universal templates for the synthesis of ring
      shaped core-shell nanostructures. As an example we used silica nanorings (with
      diameter of ~200 nm) to create a novel plasmonic nanoparticle topology, a silica
      Au core-shell nanoring, by self-assembly of Au nanoparticles (<20 nm) on the
      ring's surface. Spectroscopic measurements and finite difference time domain
      simulations reveal high quality factor multipolar and antibonding surface plasmon
      resonances in the near-infrared. By loading different types of nanoparticles on
      the silica core, hybrid and multifunctional composite nanoring structures could
      be realized for applications such as MRI contrast enhancement, catalysis, drug
      delivery, plasmonic and magnetic hyperthermia, photoacoustic imaging, and
      biochemical sensing.

PMID- 27031365
TI  - A lyophilized sterically stabilized liposome-containing docetaxel: in vitro and
      in vivo evaluation.
AB  - OBJECTIVES: In this study, an improved lyophilized PEGylated liposomal
      formulation of docetaxel (DOC) has been developed. METHODS: PEGylated docetaxel
      liposome (PL-DOC) was prepared by thin-film evaporation method and
      lyophilization. The effect of various components of the lipids and their
      compatibility with DOC on the entrapment efficiency (EE) of liposome was
      investigated. The lyophilized PL-DOC was characterized by morphology, particle
      size, zeta potential, EE, release in vitro and stability. Pharmacokinetics and
      biodistribution in vivo of lyophilized PL-DOC were also investigated. RESULTS:
      The optimal liposome formulation was egg phosphatidylcholine (EPC):cholesterol
      (CH):DSPE-PEG2000:DOC = 56:40:4:4 (molar ratio). Sucrose and mannitol were chosen
      as cryoprotectant in the lyophilization (cryoprotectant-to-lipid (C/L) mass ratio
      = 8:1). The size of lyophilized PL-DOC was 152.3 +/- 1.0 nm with negative charge
      and the EE was 89.75 +/- 1.79%. Compared with nonlyophilized PL-DOC, the
      lyophilized PL-DOC was more stable at 4  degrees C for six months. The
      lyophilized PL-DOC also showed the good stability after reconstituted by 5%
      glucose injection. In vitro release study of PL-DOC showed that PL-DOC had a
      sustained release effect. After i.v. administration at the dose of 10 mg/kg in
      rats, a significant increase in the AUC0-infinity, MRT0-infinity and t1/2 was
      observed in PL-DOC group compared with conventional docetaxel liposome (CL-DOC)
      and DOC injection (DOC-I) group. Biodistribution studies in mice showed that PL
      DOC significantly decreased the uptake by the organs of mononuclear phagocytic
      system (MPS), such as liver and spleen, while prolonging the retention time of
      DOC in the plasma. CONCLUSION: Our PEGylated liposome formulation reported in
      this study could potentially produce viable clinical strategies for improved
      delivery of DOC for the treatment of human cancer.

PMID- 27031366
TI  - Fictibacillus halophilus sp. nov., from a microbial mat of a hot spring atop the
      Himalayan Range.
AB  - A Gram-stain-positive staining, motile, endospore forming and moderately
      halophilic bacterium, designated as strain AS8T, was isolated from a microbial
      mat deposited at thermal discharges of Manikaran hot spring (with surface water
      temperature ~95  degrees C) located in Himachal Pradesh, India. 16S rRNA gene
      sequence based phylogenetic analysis revealed that strain AS8T belonged to the
      genus Fictibacillus with the highest sequence similarity to Fictibacillus
      nanhaiensis DSM 23009T (99.9 %) and Fictibacillus phosphorivorans Ca7T (99.9 %),
      followed by Fictibacillus barbaricus V2-BIII-A2T (99.1 %) and Fictibacillus
      arsenicus Con a/3T (97.4 %). The polar lipids fraction consisted of
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The
      cell-wall peptidoglycan was of the type A1gamma based on directly cross-linked
      meso-diaminopimelic acid. The DNA G+C content of strain AS8T was found to be 46.9
      mol%. The quinone system of strain AS8T consisted of MK-7 predominantly, and the
      polyamine pattern primarily contained spermidine and spermine. The major cellular
      fatty acids in strain AS8T were iso-C15:0, anteiso-C15:0 and iso-C16:0. The
      strain showed DNA-DNA relatedness of 52.7 % with F. nanhaiensis DSM 23009T, 50.7
      % with F. phosphorivorans Ca7T, 34.8 % with F. barbaricus V2-BIII-A2T and 38.0 %
      with F. arsenicus Con a/3T. In spite of the high 16S rRNA gene sequence
      similarities, the DNA-DNA hybridization and gyr B gene sequencing results (<=87
      %) supported by physiological and biochemical tests demonstrated that strain AS8T
      is a representative of a novel species, for which the name Fictibacillus
      halophilus sp. nov. is proposed. The type strain is AS8T (=MCC 2765T=DSM
      100124T=KCTC 33758T). 

PMID- 27031367
TI  - In vitro effect of 4-pentylphenol and 3-methyl-4-nitrophenol on murine splenic
      lymphocyte populations and cytokine/granzyme production.
AB  - Gasoline exhaust particles (GEP) and diesel exhaust particles (DEP) are
      considered to be some of the most important air pollutants. Among the many
      constituents in these pollutant particles, 4-pentylphenol (PP) and 3-methyl-4
      nitrophenol (PNMC) are considered important phenolics in GEP and DEP,
      respectively. The aim of this study was to investigate the effect of in vitro
      exposure to commercially-supplied PP and PNMC on populations of, and production
      of interleukin (IL)-2, IL-4 and granzyme-B by, mouse splenic lymphocytes. After
      in vitro exposure to PP or PNMC for 48 h, splenocyte viability was measured, cell
      phenotypes, e.g. B-cell (CD19), T-cells (CD3), T-cell subsets (CD4 and CD8), were
      quantified by flow cytometry and production of IL-2, IL-4 and granzyme-B was
      assessed via ELISA. The oxidative toxicity of PP and PNMC toward the splenocytes
      was also evaluated using measures of hydroxyl radical and malondiadehyde
      production and changes in glutathione peroxidase and superoxide dismutase
      activities. Results showed that in vitro exposure to PP and PNMC inhibited
      splenic cell parameters in a dose-related manner. Exposure to PP and PNMC
      decreased splenic T-lymphocyte populations and splenocyte production of cytokines
      and granzyme B, as well as induced oxidative stress in the splenocytes. The
      results also showed that the percentages of CD3(+) T-cells overall and of CD4(+)
      and CD8(+) T-cells therein, among exposed splenocytes, were reduced; neither
      compound appeared to affect levels of CD19(+) B-cells. Overall, the suppressive
      effects of PP were stronger than PNMC. The data here provide support for the
      proposal that PP-/PNMC-induced toxicity in splenocytes may be due at least in
      part to oxidative damage and that PP and PNMC - as components of GEP and DEP -
      might significantly impact on splenic T-cell formation/release of
      cytokines/granzymes in situ.

PMID- 27031368
TI  - Profile of Ventana ALK (D5F3) companion diagnostic assay for non-small-cell lung
      carcinomas.
AB  - The development of several ALK inhibitors means that the importance of accurately
      identifying ALK-positive lung cancer has never been greater. Therefore, it is
      crucial that ALK testing assays become more standardized. The aim of this review
      is to comment on the recently FDA-approved VENTANA ALK (D5F3) Companion
      Diagnostic (CDx) Assay. This kit provides high sensitivity and specificity for
      the detection of ALK rearrangements and seamless integration into the laboratory
      workflow, with a fully automated analytical phase and fast interpretation. The
      use of controls increases the sensitivity and specificity and a dichotomous
      scoring approach enhances reproducibility.

PMID- 27031369
TI  - Cytokinin signaling promotes differential stability of type-B ARRs.
AB  - Cytokinins control key aspects of plant growth, including shoot and root meristem
      development and the timing of senescence of leaves and stems. Cytokinin
      perception triggers a 2-component signaling mechanism that ultimately leads to
      phosphorylation-dependent activation of a class of transcriptional regulators
      called type-B ARRs (RRBs). We have recently shown that the stability of the RRB
      family member ARR1 is increased in response to elevated cytokinin concentrations.
      In contrast, cytokinin decreases the stability of the closely related RRB member
      ARR2. The molecular mechanism governing the differential stability regulation of
      these 2 closely related RRBs remains unknown. 

PMID- 27031370
TI  - Rhodococcus pedocola sp. nov. and Rhodococcus humicola sp. nov., two antibiotic
      producing actinomycetes isolated from soil.
AB  - Two novel actinobacterial strains, UC12T and UC33T, were isolated from forest
      topsoil in Suwon, Gyeonggi-Do, South Korea. Comparative analysis of nearly full
      length 16S rRNA gene sequences of UC12T and UC33T revealed close pairwise
      similarity with species of the genus Rhodococcus, and the UC12T and UC33T
      sequences were most closely related to Rhodococcus canchipurensis MBRL 353T
      (98.91 % 16S rRNA gene sequence similarity) and Rhodococcus triatomae IMMIB RIV
      085T (97.71 %), respectively. DNA-DNA hybridization showed 33.05-35.60 % genomic
      similarity between strains UC12T and UC33T, while strain UC12T shared DNA-DNA
      relatedness values of 32.71-41.29 % with the closest species of the genus
      Rhodococcus and strain UC33T shared 29.12-37.91 % genomic relatedness with the
      closest species of the genus Rhodococcus. Both strains showed similar
      chemotaxonomic characteristics. The major fatty acids were C16 : 0, summed
      feature 3, C18 : 1omega9c and C18 : 0 10-methyl. The polar lipids were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and
      phosphatidylinositol mannoside. The major quinone derived was MK-8(H2). The cell
      wall peptidoglycan contained meso-diaminopimelic acid, and galactose, glucose,
      arabinose and ribose were detected in whole cells. Mycolic acids were detected.
      The DNA G+C content of strains UC12T and UC33T was 72.7 mol% and 68.8 mol%,
      respectively. Both strains produced antibiotic(s) that inhibited bacterial
      pathogens but not fungi. Based on the physiological, biochemical and genotypic
      features and the DNA-DNA hybridization between the isolates and type strains of
      closely related species, we propose that these bacteria be classified as novel
      species of the genus Rhodococcus with the names Rhodococcus pedocola sp. nov.
      (type strain UC12T=KACC 18499T=NBRC 111580T) and Rhodococcus humicola sp. nov.
      (type strain UC33T=KACC 18500T=NBRC 111581T). 

PMID- 27031371
TI  - Bilateral macular holes and a new onset vitelliform lesion in Best disease.
AB  - BACKGROUND: Best vitelliform macular dystrophy (BVMD) is an autosomal dominant
      hereditary retinal disease caused by BEST1 gene mutations. Macular hole is a rare
      complication of BVMD. We are the first to report a BVMD case with bilateral
      macular holes and a new onset vitelliform lesion after a vitrectomy surgery.
      MATERIALS AND METHODS: A woman with a history of BVMD suffered from a 1-year
      vision loss in both eyes. Complete ophthalmologic examinations and BEST1 gene
      screening were performed on the patient. RESULTS: Ophthalmoscopic examinations
      revealed bilateral macular holes with atrophic photoreceptors and retinal pigment
      epithelium (RPE). A disease-causing BEST1 mutation N296S (c.887A>G) was detected.
      A vitrectomy surgery with internal limiting membrane (ILM) peeling and gas
      tamponade was performed on the right eye. The macular hole closed and maintained
      stable for 1 year. A new extramacular vitelliform lesion was observed during the
      follow-up. CONCLUSIONS: Macular hole is an unusual but severe complication in the
      end stage of BVMD as the macular thinning is accompanied with vitreous traction.
      A vitrectomy surgery is effective to close the hole while further study is
      required to elucidate the pathophysiology of macular hole formation and the new
      vitelliform lesion in such a case.

PMID- 27031372
TI  - Association of Diabetic Microvascular Complications and Parameters of Obstructive
      Sleep Apnea in Patients with Type 2 Diabetes.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in patients with type 2
      diabetes, but the influence of OSA on diabetes complications is not clear. We
      aimed to investigate the association of OSA with chronic diabetes complications
      in Chinese patients with type 2 diabetes. SUBJECTS AND METHODS: In total, 880
      hospitalized patients were enrolled in a multicenter, cross-sectional study that
      involved 12 hospitals from six cities in the People's Republic of China.
      Overnight sleep monitoring with a portable monitor was used to record respiratory
      parameters, including the apnea-hypopnea index (AHI), the oxygen desaturation
      index (ODI), the oxygen saturation (SPO2), and the cumulative time of SPO2 below
      90% or 85% (CT90% and CT85%, respectively). Chronic diabetes complications were
      recorded from medical charts. RESULTS: CT90% was independently associated with
      diabetic nephropathy (DN) after adjusting for age, sex, diabetes duration,
      glycosylated hemoglobin, body mass index, hypertension, and the use of
      angiotensin converting enzyme inhibitor/angiotensin receptor blocker drugs within
      1 week. The associated parameters increased from two (the average SPO2 and CT90%)
      to three (ODI, the lowest SPO2, and CT85%) when the severity of DN increased from
      microalbuminuria to renal insufficiency. The estimated glomerular filtration rate
      was independently correlated with ODI (beta = -0.172, P = 0.029) and the lowest
      SPO2 (beta = 0.354, P = 0.004) after adjustments. The lowest SPO2 was associated
      with proliferative diabetic retinopathy by univariate logistic regression but was
      not significant in multivariate regression after adjustment. CONCLUSIONS:
      Parameters of nocturnal hypoxemia are associated with DN and renal function of
      patients with type 2 diabetes. The parameters of hypoxemia may more sensitively
      reflect the association of OSA and diabetic microvascular complications than AHI.

PMID- 27031373
TI  - Prebiotics and Bioactive Milk Fractions Affect Gut Development, Microbiota, and
      Neurotransmitter Expression in Piglets.
AB  - OBJECTIVE: This study tested the hypothesis that the addition of prebiotics and 2
      functional milk ingredients to infant formula would maintain normal growth and
      gut development, and modify microbiota composition and neurotransmitter gene
      expression in neonatal piglets. METHODS: Two-day-old male piglets (n = 24) were
      fed formula (CONT) or formula with polydextrose (1.2 g/100 g diet),
      galactooligosaccharides (3.5 g/100 g diet), bovine lactoferrin (0.3 g/100 g
      diet), and milk fat globule membrane-10 (2.5 g/100 g diet) (TEST) for 30 days. On
      study day 31, intestinal samples, ileal and colonic contents, and feces were
      collected. Intestinal histomorphology, disaccharidase activity, serotonin (5'HT),
      vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH) were measured.
      Gut microbiota composition was assessed by pyrosequencing of the V3-V5 regions of
      16S rRNA and quantitative polymerase chain reaction. RESULTS: Body weight of
      piglets on TEST was greater (P <= 0.05) than CONT on days 17 to 30. Both groups
      displayed growth patterns within the range observed for sow-reared pigs. TEST
      piglets had greater jejunal lactase (P = 0.03) and higher (P = 0.003) ileal VIP
      expression. TEST piglets tended to have greater (P = 0.09) sucrase activity,
      longer (P = 0.08) ileal villi, and greater (P = 0.06) duodenal TH expression.
      Microbial communities of TEST piglets differed from CONT in ascending colon (AC,
      P = 0.001) and feces (P <= 0.05). CONT piglets had greater relative abundances of
      Mogibacterium, Collinsella, Klebsiella, Escherichia/Shigella, Eubacterium, and
      Roseburia compared with TEST piglets in AC. In feces, CONT piglets harbored lower
      (P <= 0.05) proportions of Parabacteroides, Clostridium IV, Lutispora, and
      Sutterella than TEST piglets. CONCLUSIONS: A mixture of bioactive ingredients
      improved weight gain and gut maturation, modulated colonic and fecal microbial
      composition, and reduced the proportions of opportunistic pathogens.

PMID- 27031374
TI  - Spanish and English Language Symposia to Enhance Activation in Pediatric
      Inflammatory Bowel Disease.
AB  - OBJECTIVES: Patient activation is an important consideration for improved health
      outcomes in the management of chronic diseases. Limited English proficiency among
      patients and primary care providers has been shown to be a predictor for worse
      health across disease states. We aimed to determine the baseline patient
      activation measure (PAM) among Spanish-speaking (SP) and English-speaking (ES)
      pediatric patients with IBD and parents, and to describe the feasibility and
      efficacy of a novel peer-group education symposium designed to enhance patient
      activation as measured with the PAM. METHODS: Two separate half-day educational
      symposia in either Spanish or English were presented and moderated by 2 native SP
      physicians. Content for each of the presentations were highly standardized and
      interactive, designed to address each of the activation domains (self-management,
      collaboration with a health care provider, maintenance of function and prevention
      of disease exacerbation, and appropriate access to high-quality care).
      Descriptive statistics were used to describe changes between pre- and
      postsymposium PAM trends. RESULTS: Eleven primarily SP and 21 ES families
      participated in their respective symposium. Paired pre- and post-PAM scores were
      available from 24 pediatric patients with IBD (8 SP, 16 ES) and 41 parents (15
      SP, 26 ES). The mean age for SP and ES patients was 11.6 and 12.0 years, and
      female sex in 80% and 62%, respectively. Paired pre- and post-PAM scores for all
      participants (n = 65) were analyzed. PAM scores uniformly increased in all 4
      groups after the symposia (SP patients 59.1-70.3, P = 0.05; SP parents 69.8-75.2,
      P = 0.2; ES patients 59.9-64.0, P = 0.08; ES parents 61.9-69.1, P = 0.002),
      although only the ES-parents group had sufficient sample size (n = 26) to achieve
      statistical significance. The overall cohort had an aggregate increase from pre
      PAM of 62.9 (SD 14.5) to post-PAM of 69.4 (SD 13.9) (<0.001). CONCLUSIONS: We
      describe a novel peer-group educational symposium presented in Spanish and
      English languages to increase patient and parent activation in pediatric patients
      with IBD and their caregiving parents. The use of PAM to assess levels of
      activation appears to be feasible and effective in these groups.

PMID- 27031375
TI  - Why all women should freeze their eggs.
AB  - PURPOSE OF REVIEW: The use of oocyte cryopreservation via vitrification has
      increased lately, becoming a common strategy in many IVF centers. This review
      summarizes the current state of oocyte vitrification, by analyzing the most
      recent reports on its use in IVF as part of infertile treatment and its
      contribution to elective fertility preservation (EFP). RECENT FINDINGS: Oocyte
      vitrification has become helpful for managing different clinical situations
      currently providing similar results to fresh oocytes. Owing to satisfactory
      results, oocyte vitrification is being offered to healthy women to extend their
      reproductive options (EFP). Although little is known about outcomes in this
      specific population, new evidence is starting to emerge. Currently, most women
      are motivated by age and lack of partner. Age is strongly related to the
      probability of having a child with better chances when they do EFP younger than
      35. In contrast to the biological efficiency, the majority of studies show that
      EFP is more cost-effective at 37-38 years. SUMMARY: Oocyte vitrification is an
      efficient tool which can be helpful in managing the IVF cycle. Fertility
      preservation providers should inform women about their specific probabilities
      according to their age at vitrification, making emphasis in the fact that egg
      freezing does not guarantee success, but increases the possibilities of having a
      biological child in the future.

PMID- 27031376
TI  - Clinical value of dual-energy spectral imaging with adaptive statistical
      iterative reconstruction for reducing contrast medium dose in CT portal
      venography: in comparison with standard 120-kVp imaging protocol.
AB  - OBJECTIVE: To evaluate the clinical value of dual-energy spectral CT with
      adaptive statistical iterative reconstruction (ASiR) for reducing contrast medium
      dose in CT portal venography (CTPV). METHODS: This prospective study was
      institutional review board-approved, and written informed consent was obtained
      from all patients. 50 patients undergoing abdominal CT were randomized to 2
      groups: Group A (n = 25), using spectral CT and 350 mgI kg(-1) contrast injection
      protocol; Group B (n = 25), using standard 120 kVp and 500 mgI kg(-1) contrast.
      Spectral CT images at 60 keV and standard 120-kVp images were both reconstructed
      with 50% ASiR. CT number and contrast-to-noise ratio (CNR) for intrahepatic and
      extrahepatic portal veins were measured. The maximum intensity projection (MIP)
      and volume-rendering (VR) images were used for subjective evaluation. These two
      kinds of results were statistically analyzed. RESULTS: CNR values for the
      intrahepatic portal vein of the 60-keV spectral images (4.2 +/- 1.1) were higher
      than those of 120-kVp images (3.0 +/- 2.1) (p = 0.03) and were the same for the
      extrahepatic portal vein (5.9 +/- 1.4 vs 5.9 +/- 1.6, p = 0.90). The portal vein
      and left and right branches in the 60-keV spectral images had higher CT number
      and lower standard deviation than the 120-kVp images (p < 0.05). Radiation dose
      (dose-length product and effective dose) and subjective image quality were
      similar for the two groups, while the spectral CT group required 25% less iodine
      dose (23.1 +/- 3.2 g vs 30.5 +/- 5.0 g). CONCLUSION: The 60-keV spectral CT
      images with ASiR allow 25% reduction in the iodine dose while providing better or
      equal image quality as the standard 120-kVp images in portal venography with
      comparable radiation dose. ADVANCES IN KNOWLEDGE: Compared with conventional 120
      kVp CT, the use of 60-keV spectral CT images provides 25% contrast dose reduction
      with similar image quality in CTPV. Compared with conventional 120-kVp CT, the
      use of 60-keV spectral CT images with ASiR algorithm improves CNR values for the
      intrahepatic portal vein.

PMID- 27031377
TI  - Mass of the Anterior Nasal Septum.

PMID- 27031378
TI  - Curriculum Development and Evaluation of a Hemodynamic Critical Care Ultrasound:
      A Systematic Review of the Literature.
AB  - OBJECTIVE: The application of ultrasound to assess a patient's cardiac function
      and volume status is becoming commonplace in the practice of critical care. These
      skills have been taught through varying curricula; however, no consensus on the
      optimal curriculum has been established. The purpose of this systematic review is
      to evaluate the literature regarding critical care ultrasound curriculum
      development and evaluation. DATA SOURCES: Studies were identified using MEDLINE,
      Embase, CINAHL, PsycInfo, the Cochrane Center Register of Controlled Trials, and
      ERIC according to Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines through June 2014. STUDY SELECTION: Included studies were
      limited to those that described adult (age, > 16 yr) cardiac or hemodynamic
      critical care ultrasound curricula for physicians. Two reviewers independently
      screened studies based on predetermined exclusion criteria, and disagreements
      were resolved by a third reviewer. DATA EXTRACTION: Data were abstracted, and
      quality was assessed by two reviewers using the Newcastle-Ottawa Scale. Data
      abstracted from the studies included the learner population, examination type,
      duration, composition, and setting of the curriculum, means of evaluation, and
      outcomes. DATA SYNTHESIS: The search yielded 654 studies; of which, 15 met
      inclusion criteria. All curricula used a combination of didactic and hands-on
      components. The highest agreement between novice and experts, coupled with the
      most time-efficient application, was achieved when the study was limited to a
      basic qualitative approach for the assessment of global function or contractility
      and assessment of inferior vena cava collapsibility. The mode of delivery seemed
      most efficient when a hybrid method was used, including online instruction.
      Minimum scanning competency may be achieved with 30 scans although more rigorous
      study on this element is necessary. CONCLUSIONS: Assessment of cardiac function
      and volume assessment is becoming an essential skill in critical care medicine.
      Physicians can be taught bedside echocardiography in a time-effective manner with
      positive benefit to patients by applying a concise curriculum with limited
      content.

PMID- 27031379
TI  - Treating Life-Threatening Myocarditis by Blocking Interleukin-1.
AB  - OBJECTIVE: Treatment of viral fulminant myocarditis relies on life support
      measures. Based on studies pointing to a role for the proinflammatory cytokine
      interleukin-1 in myocardial inflammation and contractile dysfunction, we treated
      a patient with fulminant viral myocarditis with the interleukin-1 receptor
      blocking agent anakinra. We report the response and discuss the biologic
      rationale of this novel treatment approach. DESIGN: Case report. SETTING: ICU.
      PATIENT: A 36-year-old woman who was hospitalized for fulminant myocarditis with
      biventricular failure and cardiogenic shock, acutely manifested with hypotension
      and dyspnea. INTERVENTIONS: Following the progressive, life-threatening collapse
      of the cardiac function in spite of treatment with venous-arterial extracorporeal
      membrane oxygenation and mechanical circulatory support with a left ventricular
      assist device, treatment with the interleukin-1 receptor blocking agent anakinra
      100 mg/d was started. MEASUREMENTS AND MAIN RESULTS: The severe depression of
      cardiac function responded promptly to interleukin-1 inhibition. Within 4 days of
      treatment initiation, progressive clinical improvement allowed weaning from
      extracorporeal membrane oxygenation and removal of the percutaneous left
      ventricular assist device. The patient was discharged home and remains in
      excellent health at 12 months. CONCLUSIONS: Clinical and experimental evidence
      suggests that interleukin-1 blockade is effective against myocardial inflammation
      and contractile dysfunction, thus representing a promising candidate for the
      treatment of inflammatory heart failure. Although further confirmation is needed,
      these encouraging results indicate that anakinra may be a suitable treatment for
      fulminant myocarditis.

PMID- 27031380
TI  - Delayed Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase
      Inhibition by Trametinib Attenuates Systemic Inflammatory Responses and Multiple
      Organ Injury in Murine Sepsis.
AB  - OBJECTIVE: The mitogen-activated protein kinase/extracellular signal-regulated
      kinase signaling pathway is an essential component of innate immunity necessary
      for mediating proinflammatory responses in the setting of sepsis. We previously
      demonstrated that the mitogen-activated protein kinase 1/2 inhibitor trametinib
      prevents endotoxin-induced renal injury in mice. We therefore assessed efficacy
      of trametinib in a more clinically relevant experimental model of sepsis. DESIGN:
      Controlled in vivo laboratory study. SETTING: University animal research
      laboratory. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Mice were subjected to
      cecal ligation and puncture to induce sepsis or underwent sham operation as
      controls. Six hours after cecal ligation and puncture, mice were randomized to
      four experimental groups as follows: 1) sham control; 2) sham control +
      trametinib (1 mg/kg, IP); 3) cecal ligation and puncture; and 4) cecal ligation
      and puncture + trametinib. All animals received buprenorphine (0.05 mg/kg, SC)
      and imipenem/cilastatin (14 mg/kg, SC) in 1.5 mL of warm saline (40 mL/kg) at the
      6-hour time point. Mice were euthanized at 18 hours after induction of cecal
      ligation and puncture. MEASUREMENTS AND MAIN RESULTS: Trametinib inhibition of
      mitogen-activated protein kinase/extracellular signal-regulated kinase signaling
      6 hours after cecal ligation and puncture attenuated increases in circulating
      proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta,
      interleukin-6, and granulocyte macrophage colony-stimulating factor) and
      hypothermia at 18 hours. Trametinib also attenuated multiple organ injury as
      determined by serum creatinine, alanine aminotransferase, lactate dehydrogenase,
      and creatine kinase. At the organ level, trametinib completely restored
      peritubular capillary perfusion in the kidney. Restoration of microvascular
      perfusion was associated with reduced messenger RNA expression of well
      characterized markers of proximal tubule injury. mitogen-activated protein
      kinase/extracellular signal-regulated kinase blockade attenuated cecal ligation
      and puncture-mediated up-regulation of cytokines (tumor necrosis factor-alpha,
      interleukin-1beta) and restored interleukin-6 to control levels in the renal
      cortex, indicating the protective effects on the proximal tubule occur primarily
      through modulation of the proinflammatory response in sepsis. CONCLUSIONS: These
      data reveal that the mitogen-activated protein kinase/extracellular signal
      regulated kinase inhibitor trametinib attenuates systemic inflammation and
      multiple organ damage in a clinically relevant model of sepsis. Because
      trametinib has been safely used in humans, we propose that this drug might
      represent a translatable approach to limit organ injury in septic patients.

PMID- 27031381
TI  - Derivation of Novel Risk Prediction Scores for Community-Acquired Sepsis and
      Severe Sepsis.
AB  - OBJECTIVE: We sought to derive and internally validate a Sepsis Risk Score and a
      Severe Sepsis Risk Score predicting future sepsis and severe sepsis events among
      community-dwelling adults. DESIGN: National population-based cohort. SETTING:
      United States. SUBJECTS: A total of 30,239 community-dwelling adults 45 years old
      or older in the national REasons for Geographic And Racial Differences in Stroke
      cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over a median of 6.6
      years (interquartile range, 5.1-8.1 yr) of follow-up, there were 1,532 first
      sepsis (prevalence 8.3 per 1,000 person-years) and 1,151 first severe sepsis (6.2
      per 1,000 person-years) events. Risk factors in the best derived Sepsis Risk
      Score and Severe Sepsis Risk Score included chronic lung disease, age 75 years or
      older, peripheral artery disease, diabetes, tobacco use, white race, stroke,
      atrial fibrillation, coronary artery disease, obesity, hypertension, deep vein
      thrombosis, male sex, high-sensitivity C-reactive protein greater than 3.0 mg/dL,
      cystatin C >=1.11 mg/dL, estimated glomerular filtration rate less than 60
      mL/min/1.73 m, and albumin-to-creatinine ratio protein greater than 30 MUg/mg.
      Sepsis Risk Score risk categories were very low (0-3 points; 2.3 events per 1,000
      person-years), low (4-6; 4.1), medium (7-9; 6.5), high (10-12; 9.7), and very
      high (13-38; 21.1). Severe Sepsis Risk Score risk categories were very low (0-5
      points; 1.5 events per 1,000 person-years), low (6-9; 3.4), medium (10-13; 6.7),
      high (14-17; 9.9), and very high (18-45; 22.1). The Sepsis Risk Score and Severe
      Sepsis Risk Score exhibited good discrimination (bootstrapped C index, 0.703 and
      0.742) and calibration (p = 0.65 and 0.06). CONCLUSIONS: The Sepsis Risk Score
      and Severe Sepsis Risk Score predict 10-year sepsis and severe sepsis risk among
      community-dwelling adults and may aid in sepsis prevention or mitigation efforts.

PMID- 27031384
TI  - Doctor, Heal Thyself: Treatment Seeking for Stress and Health Researchers.

PMID- 27031383
TI  - Pharmacokinetic and Pharmacodynamic Investigations of ION-353382, a Model
      Antisense Oligonucleotide: Using Alpha-2-Macroglobulin and Murinoglobulin Double
      Knockout Mice.
AB  - To investigate the pharmacokinetics (PKs) and pharmacodynamics (PDs) for ION
      353382, an antisense oligonucleotide (ASO) targeting scavenger receptor class B
      type I (SRB1) mRNA, using alpha-2-macroglobulin (A2M), murinoglobulin double
      knockout (DKO), and wild-type mice. Wild-type and DKO homozygous mice were
      administered a single subcutaneous injection of ION-353382 at 0, 5, 15, 30, and
      60 mg/kg. Mice were sacrificed at 72 h with plasma and organs harvested. Both
      liquid chromatography-mass spectrometry (LC-MS) and enzyme-linked immunosorbent
      assay (ELISA) were used to determine ASO exposure with real-time PCR for SRB1
      expression. Immunohistochemistry was evaluated to explore hepatic uptake of ASOs.
      The total plasma protein binding and profiling was assessed. Finally, two
      dimensional gel electrophoresis identified protein expression differences. PK
      exposures were comparable between wild-type and DKO mice in plasma, liver, and
      kidney, yet a near twofold reduction in EC50 was revealed for DKO mice based on
      an inhibitory effect liver exposure response model. Total plasma protein binding
      and profiling revealed no major dissimilarities between both groups. Plasma
      proteome fingerprinting confirmed protein expression variations related to A2M.
      Histological examination revealed enhanced ASO distribution into hepatocytes and
      less nonparenchymal uptake for DKO mice compared to wild-type mice. Knocking out
      A2M showed improved PD activities without an effect on total plasma and tissue
      exposure kinetics. Binding to A2M could mediate ASOs to nonproductive
      compartments, and thus, decreased binding of ASOs to A2M could potentially
      improve ASO pharmacology.

PMID- 27031382
TI  - Hospital Variation in Early Tracheostomy in the United States: A Population-Based
      Study.
AB  - OBJECTIVE: Controversy exists regarding perceived benefits of early tracheostomy
      to facilitate weaning among mechanically ventilated patients, potentially leading
      to significant practice-pattern variation with implications for outcomes and
      resource utilization. We sought to determine practice-pattern variation and
      outcomes associated with tracheostomy timing in the United States. DESIGN: In a
      retrospective cohort study, we identified mechanically ventilated patients with
      the most common causes of respiratory failure leading to tracheostomy:
      pneumonia/sepsis and trauma. "Early tracheostomy" was performed within the first
      week of mechanical ventilation. We determined between-hospital variation in early
      tracheostomy utilization and the association of early tracheostomy with patient
      outcomes using hierarchical regression. SETTING: 2012 National Inpatient Sample.
      PATIENTS: A total of 6,075 pneumonia/sepsis patients and 12,030 trauma patients
      with tracheostomy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Trauma
      patients were twice as likely as pneumonia/sepsis patients to receive early
      tracheostomy (44.5% vs 21.7%; p < 0.001). Admission to hospitals with higher
      early tracheostomy-to-total-tracheostomy ratios was associated with increased
      risk for tracheostomy among mechanically ventilated trauma patients (adjusted
      odds ratio = 1.04; 95% CI, 1.01-1.07) but not pneumonia/sepsis (adjusted odds
      ratio =1.00; 95% CI, 0.98-1.02). We observed greater between-hospital variation
      in early tracheostomy rates among trauma patients (21.9-81.9%) compared with
      pneumonia/sepsis (14.9-38.3%; p < 0.0001). We found no evidence of improved
      hospital mortality. Pneumonia/sepsis patients with early tracheostomy had fewer
      feeding tube procedures and higher odds of discharge home. CONCLUSION: Early
      tracheostomy is potentially overused among mechanically ventilated trauma
      patients, with nearly half of tracheostomies performed within the first week of
      mechanical ventilation and large unexplained hospital variation, without clear
      benefits. Future studies are needed to characterize potentially differential
      benefits for early tracheostomy between disease subgroups and to investigate
      factors driving hospital variation in tracheostomy timing.

PMID- 27031385
TI  - Unicameral Bone Cyst of the Medial Cuneiform.
AB  - A unicameral bone cyst is a relatively uncommon, benign bone tumor found in the
      metaphysis of long bones, such as the humerus and the femur, in skeletally
      immature persons. In the foot, these benign, fluid-filled cavities are most
      commonly found within the os calcis. We present a case report of a 10-year-old
      female with a unicameral bone cyst of the medial cuneiform.

PMID- 27031386
TI  - Resistance sans frontieres: containing antimicrobial resistance nationally and
      globally.

PMID- 27031387
TI  - Improving health outcomes for linguistically diverse patients.

PMID- 27031388
TI  - Ethical issues with xenotransplantation clinical trials.

PMID- 27031390
TI  - Affordable access to innovative cancer medicines - don't forget the prices.

PMID- 27031391
TI  - Closing the million patient gap of uncontrolled asthma.

PMID- 27031392
TI  - Alcohol and tax - time for real reform.

PMID- 27031393
TI  - Time to raise the minimum purchasing age for tobacco in Australia.

PMID- 27031394
TI  - Australia's health: being accountable for prevention.

PMID- 27031395
TI  - Antenatal haemoglobinopathy screening in Australia.
AB  - Haemoglobinopathy screening should be performed in women with microcytic indices,
      women from high risk ethnic populations and those with unexplained anaemia. Early
      testing of women and their partners expedites appropriate management prior to and
      during pregnancy. Haemoglobinopathy screening is a multistep process beginning
      with a full blood count, ferritin assay, screening tests for haemoglobinopathies
      (ie, haemoglobin electrophoresis, high performance liquid chromatography,
      capillary electrophoresis) and assessment of clinical risk. Iron deficiency may
      obscure the diagnosis of beta-thalassaemia trait. If possible, haemoglobinopathy
      testing should be performed when the woman is iron-replete. Genetic testing can
      be offered on the basis of the combined risk of the couple; but turnaround times
      are lengthy at present, hence the emphasis on early pregnancy or pre-conception
      screening. Screening processes vary between states and local health districts; a
      uniform approach to screening and genetic testing with a national registry to
      record results would improve management of this growing problem. 

PMID- 27031396
TI  - Serious adverse event reporting in investigator-initiated clinical trials.
AB  - Reporting adverse events (AEs) and serious AEs (SAEs) are practical steps to
      ensure safety for volunteers and patients in medical research involving
      medications, treatments and devices. However, the burden and cost of reporting
      should be proportionate with the public health benefit of this information.
      Unfortunately, in Australia there is clear evidence of ever-increasing
      requirements from sponsors and ethics committees to report AEs and SAEs
      unnecessarily, leading to a decrease in the uptake of research, particularly less
      well funded investigator-initiated trials. We believe that individual AE reports
      to ethics committees serve no useful purpose, because in most cases the study
      group identity (drug exposure) is not known in studies with blinded treatment
      arms and their value is limited. Pragmatic, investigator-initiated Phase IV
      clinical trials of post-marketed drugs or devices are needed to understand their
      role in everyday clinical practice. In this setting, the workload and costs of
      systematic, complete reporting of all AEs and SAEs (independent of whether these
      are treatment-related) is wasteful, and mostly unnecessary. A trial data safety
      and monitoring committee is in the unique position of being able to review safety
      information according to the blinded treatment arms of the study. This enables
      safety data to be analysed appropriately and a summary report provided to the
      trial steering committee, principal investigators and the relevant ethics
      committees in a meaningful way. Defined trial endpoints do not need to be
      reported as safety events (because they are being properly monitored and
      analysed). 

PMID- 27031397
TI  - Primary Health Networks and Aboriginal and Torres Strait Islander health.
AB  - The Australian Government has established that the health of Aboriginal and
      Torres Strait Islander peoples is a priority for the newly established 31 Primary
      Health Networks (PHNs). Efforts to reduce the high hospitalisation rates of
      Aboriginal people will require PHNs to build formal participatory structures with
      Aboriginal health organisations to support best practice service models. There
      are precedents as to how PHNs can build formal partnerships with Aboriginal
      community controlled health services (ACCHSs), establish an Aboriginal and Torres
      Strait Islander steering committee to guide strategic plan development, and work
      towards optimising comprehensive primary care. All health services within PHN
      boundaries can be supported to systematically and strategically improve their
      responsiveness to Aboriginal and Torres Strait Islander people by assessing
      systems of care, adopting best practice models, embedding quality assurance
      activity, and participating in performance reporting. PHNs can be guided to adopt
      an Aboriginal and Torres Strait Islander-specific quality improvement framework,
      agree to local performance measures, review specialist and other outreach
      services to better integrate with primary health care, enhance the cultural
      competence of services, and measure and respond to progress in reducing
      potentially preventable hospitalisations. Through collaborations and capacity
      building, PHNs can transition certain health services towards greater Aboriginal
      community control. These proposals may assist policy makers to develop
      organisational performance reporting on PHN efforts to close the gap in
      Aboriginal health disparity. 

PMID- 27031398
TI  - Cord blood vitamin D and the risk of acute lower respiratory infection in
      Indigenous infants in the Northern Territory.
AB  - OBJECTIVES: To assess vitamin D status in Indigenous mothers and infants in the
      Northern Territory, and to determine whether cord blood vitamin D levels are
      correlated with the risk of infant hospitalisation for acute lower respiratory
      infection (ALRI). DESIGN AND PARTICIPANTS: Within a nested cohort of 109
      Indigenous mother-infant pairs recruited between 2006 and 2011, we used liquid
      chromatography-mass spectrometry to measure vitamin D (25(OH)D3) levels in
      maternal blood during pregnancy (n = 33; median gestation, 32 weeks [range, 28-36
      weeks]) and at birth (n = 106; median gestation, 39 weeks [range, 34-41 weeks]),
      in cord blood (n = 84; median gestation, 39 weeks [range, 36-41 weeks]), and in
      infant blood at age 7 months (n = 37; median age, 7.1 months [range, 6.6-8.1
      months]). MAIN OUTCOME MEASURE: ALRI hospitalisations during the first 12 months
      of infancy, identified using International Classification of Diseases coding (J09
      J22, A37-A37.9). RESULTS: Compared with mean 25(OH)D3 levels in maternal blood
      during pregnancy (104 nmol/L), mean levels were 23% lower in maternal blood at
      birth (80 nmol/L) and 48% lower in cord blood samples (54 nmol/L). The mean cord
      blood 25(OH)D3 concentration in seven infants subsequently hospitalised for an
      ALRI was 37 nmol/L (95% CI, 25-48 nmol/L), lower than the 56 nmol/L (95% CI, 51
      61 nmol/L) in the 77 infants who were not hospitalised with an ALRI (P = 0.025).
      CONCLUSIONS: Cord blood 25(OH)D3 concentrations were about half those in maternal
      blood during the third trimester of pregnancy (about 7 weeks earlier). Most cord
      blood levels (80%) were classified as vitamin D insufficient (< 75 nmol/L) by
      existing guidelines, and were lower among infants who were subsequently
      hospitalised with an ALRI.

PMID- 27031399
TI  - English as a second language and outcomes of patients presenting with acute
      coronary syndromes: results from the CONCORDANCE registry.
AB  - OBJECTIVES: To investigate whether patients with English as their second language
      have similar acute coronary syndrome (ACS) outcomes to people whose first
      language is English. DESIGN: Retrospective, observational study, using
      admissions, treatment and follow-up data. PARTICIPANTS AND SETTING: A total of
      6304 subjects from 41 sites enrolled in the investigator-initiated CONCORDANCE
      ACS registry. MAIN OUTCOME MEASURES: Baseline characteristics, treatments, and in
      hospital and 6-month mortality. RESULTS: English as a second language (ESL) was
      reported by 1005 subjects (15.9%). Patients with English as their first language
      (EFL) were older, and were less likely to have diabetes mellitus or to smoke than
      the ESL patients. Prior myocardial infarction, heart failure and chronic renal
      failure were more common in the ESL group. In-hospital mortality was also higher
      in these patients (7.1% v 3.8% for EFL patients; P < 0.001). Predictors of in
      hospital mortality included presentation in cardiogenic shock, cardiac arrest in
      hospital, a history of renal failure, prior cardiac failure, and ESL. Rates of
      cardiac catheterisation, percutaneous coronary intervention rates, and referral
      to cardiac rehabilitation were lower in the ESL group; at 6 months, all-cause
      mortality was also higher (13.8% v 8.3% for EFL group; P < 0.001). Logistic
      regression identified language, age, in-hospital renal failure, and recurrent
      ischaemia as predictors of 6-month mortality. CONCLUSION: Patients presenting
      with an ACS who report English as their second language have poorer outcomes than
      patients who use English as their first language. This difference may not be
      entirely explained by baseline demographic disparities or management differences.

PMID- 27031400
TI  - Increase in late diagnosed developmental dysplasia of the hip in South Australia:
      risk factors, proposed solutions.
AB  - OBJECTIVES: To review evidence for the increased incidence of late diagnosed
      developmental dysplasia of the hip (DDH) in South Australia; to identify
      perinatal risk factors associated with late DDH in babies born between 2003 and
      2009 in SA. DESIGN: Linkage study of data collected prospectively by the South
      Australian Birth Defects Register (SABDR) and the Pregnancy Outcome Statistics
      Unit (SA Department of Health), supplemented by medical records review.
      PARTICIPANTS: All children born 2003-2009 in whom DDH was diagnosed between 3
      months and 5 years of age and notified to the SABDR (data inclusion range, 2003
      2014). Children with teratological hip dislocations and other major congenital
      abnormalities were excluded. MAIN OUTCOME MEASURES: Uni- and multivariable
      analyses were performed to identify perinatal risk factors for late diagnosed
      DDH. RESULTS: The incidence of late diagnosed DDH in babies born 2003-2009 was
      0.77 per 1000 live births, contrasting with the figure of 0.22 per 1000 live
      births during 1988-2003. Significant perinatal risk factors were birth in a rural
      hospital (v metropolitan public hospital: odds ratio [OR], 2.47; CI, 1.37-4.46; P
      = 0.003), and being the second child (v being the first-born: OR, 1.69; CI, 1.08
      2.66; P = 0.023). Breech presentation was highly significant as a protective
      factor when compared with cephalic presentation (OR, 0.25; CI, 0.12-0.54; P <
      0.001). CONCLUSIONS: The incidence of late DDH has increased in SA despite an
      ongoing clinical screening program. Increased awareness, education, and avoidance
      of inappropriate lower limb swaddling are necessary to reverse this trend.

PMID- 27031401
TI  - Pitfalls of open-access sleep medicine: a case of missed congenital central
      hypoventilation syndrome.

PMID- 27031404
TI  - Influence of Tacticity on Hydrophobicity of Poly(N-isopropylacrylamide): A Single
      Chain Molecular Dynamics Simulation Study.
AB  - Several pieces of experimental evidence show that the water affinity of poly(N
      isopropylacrylamide), PNIPAM, decreases with the increase of the degree of
      isotacticity. To give a rationale to such effect we carried out atomistic
      molecular dynamics simulations of PNIPAM 30-mers with content of meso dyads, m,
      of 45% and 59%, assuming a Bernoullian dyad distribution. The single chain
      behavior of these stereoisomers in water was modeled at 283 and 323 K, i.e.,
      below and above the lower critical solution temperature, LCST. Simulation results
      show that the dyad composition has influence on size and conformation of the
      oligomer below the LCST, the isotactic-rich stereoisomer preferring conformations
      with lower radius of gyration. With reference to the cooperative hydration model
      of PNIPAM, we analyzed the organization and the dynamics of water in the
      surroundings of the polymer. Below the LCST the number of hydrogen bonds per
      water molecule in the first hydration shell and the water surface concentration
      around PNIPAM are affected by the meso/racemo dyad ratio, showing the higher
      hydrophobicity of the isotactic-rich system. Above the LCST the subtle effects
      leading to the modulation of conformation and hydration by means of tacticity are
      overtaken, and the chain collapse is observed for both systems up to a similar
      globular state. The comparison of simulation findings of the m 45% stereoisomer
      with available experimental results of atactic PNIPAM highlights additional
      molecular details of this macromolecule in aqueous environment. The
      characteristic time for motion of water molecules in the PNIPAM first hydration
      shell at 283 K is about 34 ps, in agreement with the experimental value.

PMID- 27031405
TI  - Macrophage activation marker, soluble CD163, is an independent predictor of short
      term mortality in patients with cirrhosis and bacterial infection.
AB  - BACKGROUND & AIMS: Innate immune system dysfunction is common in advanced
      cirrhosis, with a central role of the monocyte/macrophage system. Monocytes and
      macrophages express the scavenger receptor CD163, which is regulated by
      inflammatory mediators. Cleavage of the receptor leads to the formation of
      soluble (s)CD163 that represents an anti-inflammatory response. We aimed to study
      the clinical importance of sCD163 in cirrhosis. METHODS: Sera of 378 patients
      were assayed for sCD163 by ELISA [193 outpatients and 185 patients with acute
      decompensation (AD)]. A 5-year follow-up observational study was conducted to
      assess the possible association between sCD163 level and poor disease outcomes.
      RESULTS: sCD163 level was associated with disease severity, but not with the
      presence of varices or prior variceal bleeding. In outpatients, sCD163 level did
      not predict the development of disease-specific complications or the long-term
      mortality. In patients with AD episode, sCD163 level was significantly higher
      compared to outpatients but only in the presence of bacterial infection (INF) (AD
      INF:4586, AD-NON-INF:3792 and outpatients: 3538 ng/ml, P < 0.015 and P = 0.001,
      respectively). sCD163 level gradually increased according to severity of
      infection. During bacterial infections, high sCD163 level (>7000 ng/ml) was
      associated with increased mortality rate (42% vs. 17%, P < 0.001) and was
      identified as an independent predictor of 28-day mortality (hazard ratio:2.96,
      95% confidence intervals:1.27-6.95) in multivariate Cox-regression model
      comprising aetiology, co-morbidity, model for end-stage liver disease score and
      leucocyte count as covariates. CONCLUSIONS: High sCD163 level is useful to
      identify patients with high-risk of death during an AD episode complicated by
      bacterial infection. This finding serves as an additional hint towards the
      significance of anti-inflammatory response during bacterial infection.

PMID- 27031406
TI  - Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives
      as Potent and Selective alpha1A-Adrenoceptor Antagonists.
AB  - A series of indoline and indole derivatives were designed, synthesized, and
      evaluated as selective alpha1A-adrenergic receptor (alpha1A-AR) antagonists for
      the treatment of benign prostatic hyperplasia (BPH). In this study, two highly
      selective and potent alpha1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM,
      alpha1B/alpha1A = 640.1, alpha1D/alpha1A = 408.2) and (R)-23l (IC50 = 1.9 nM,
      alpha1B/alpha1A = 1506, alpha1D/alpha1A = 249.6), which exhibited similar
      activities and better selectivities in cell-based calcium assays as compared with
      the marketed drug silodosin (IC50 = 1.9 nM, alpha1B/alpha1A = 285.9,
      alpha1D/alpha1A = 14.4), were identified. In the functional assays with isolated
      rat tissues, compounds (R)-14r and (R)-23l also showed high potency and
      uroselectivity. Most importantly, (R)-14r and (R)-23l can significantly decrease
      the micturition frequency and increase the mean voided volume of the BPH rats in
      a dose-dependent manner, making them worthy of further investigation for the
      development of anti-BPH agents.

PMID- 27031407
TI  - Towards understanding the improved stability of palladium supported on TS-1 for
      catalytic combustion.
AB  - A novel Pd supported on TS-1 combustion catalyst was synthesized and tested in
      methane combustion under very lean and under highly humid conditions (<1%). A
      notable increase in hydrothermal stability was observed over 1900 h time-on
      stream experiments, where an almost constant, steady state activity obtaining 90%
      methane conversion was achieved below 500  degrees C. Surface oxygen mobility and
      coverage plays a major role in the activity and stability of the lean methane
      combustion in the presence of large excess of water vapour. We identified water
      adsorption and in turn the hydrophobicity of the catalyst support as the major
      factor influencing the long term stability of combustion catalysts. While
      Pd/Al2O3 catalyst shows a higher turn-over frequency than that of Pd/TS-1
      catalyst, the situation reversed after ca. 1900 h on stream. Two linear regions,
      with different activation energies in the Arrhenius plot for the equilibrium
      Pd/TS-1 catalyst, were observed. The conclusions were supported by catalyst
      characterization using H2-chemisorption, TPD, XPS analyses as well as N2
      adsorption-desorption, XRD, SEM, TEM. The hydrophobicity and competitive
      adsorption of water with oxygen is suggested to influence oxygen surface coverage
      and in turn the apparent activation energy for the oxidation reaction.

PMID- 27031409
TI  - Simulation study compares cat population reduction methods.

PMID- 27031410
TI  - Involving ACVAA diplomates to decrease anesthetic risk.

PMID- 27031411
TI  - What Is Your Diagnosis? Tracheal foreign body (possibly a wood stick) with
      secondary pneumonia in the accessory lung lobe.

PMID- 27031412
TI  - What Is Your Neurologic Diagnosis? Myelopathy in the region of T3 through L2.

PMID- 27031413
TI  - Theriogenology Question of the Month. Anti-Mullerian hormone (AMH).

PMID- 27031414
TI  - Pathology in Practice. Diffuse, invasive, undifferentiated gastric carcinoma in a
      dog.

PMID- 27031415
TI  - Pathology in Practice. Proliferative and necrotizing enterocolitis in a pig
      resulting from coinfection with L intracellularis and S enterica.

PMID- 27031416
TI  - Urinalysis in chinchillas (Chinchilla lanigera).
AB  - OBJECTIVE: To evaluate urine variables in chinchillas (Chinchilla lanigera).
      DESIGN: Evaluation study. SAMPLE: Urine samples from 41 chinchillas. PROCEDURES:
      Voided urine samples were collected from clinically normal chinchillas that were
      exhibited during a breeder exposition. Urinalysis was performed within 1 hour
      after collection. Urine specific gravity (USG) was measured before and after
      centrifugation with a handheld veterinary refractometer. Urine dipstick analysis
      and microscopic sedimentation examination were performed on all samples.
      Additionally, a urine sulfosalicylic acid (SSA) precipitation test and
      quantitative protein analysis were performed on samples with sufficient volume.
      RESULTS: 17 of 41 (41%) samples had a USG >= 1.050, and USG ranged from 1.014 to
      > 1.060. The USG before centrifugation did not differ significantly from that
      after centrifugation. Protein was detected in all urine samples on dipstick
      analysis. The SSA precipitation test yielded negative results for all samples
      tested. Results of the quantitative protein analyses were not correlated with the
      results of the dipstick analyses or SSA tests. The recorded pH for all samples
      was 8.5, which was the upper limit of detection for the reagent strip. Glucose
      and ketones were detected in 5 and 6 samples, respectively. Crystals were
      observed in 28 of 41 (68%) samples; 27 of those samples contained amorphous
      crystals. CONCLUSIONS AND CLINICAL RELEVANCE: Urinalysis results for clinically
      normal chinchillas were provided. For chinchilla urine samples, measurement of
      USG by refractometry prior to centrifugation is acceptable and protein
      concentration should be determined by quantitative protein analysis rather than
      dipstick analysis or the SSA test.

PMID- 27031417
TI  - Characterization of leptospirosis among dogs in Oregon, 2007-2011.
AB  - OBJECTIVE: To characterize the demographics, exposure risks, and outcomes for
      dogs with leptospirosis in Oregon between 2007 and 2011 and to identify
      geographic and temporal distributions of known cases of canine leptospirosis
      within the state during this period. DESIGN: Retrospective descriptive
      epidemiological study. ANIMALS: 72 dogs. PROCEDURES: Reports of laboratory tests
      for leptospirosis and zoonosis reporting forms voluntarily submitted by
      veterinarians to the Oregon Health Authority were evaluated to identify dogs with
      leptospirosis during the study period; data were also collected by examination of
      medical records or by telephone surveys with veterinarians from reporting
      facilities. RESULTS: 72 confirmed cases of leptospirosis were identified; surveys
      were completed for 65 cases. Seasonal and spatial distributions coincided with
      rainfall patterns for the state, with most cases diagnosed in the spring and in
      the western part of the state. Common exposure risks included contact with water
      in the environment (14/65) and contact with wildlife (14); 33 dogs had no history
      of known exposure risks. Among dogs with other conditions at the time of
      diagnosis (26/64), dermatitis, otitis, or both were the most commonly reported
      findings (9/26). Of 65 dogs, 44 recovered, 12 died or were euthanized because of
      leptospirosis, and 9 were lost to follow-up. CONCLUSIONS AND CLINICAL RELEVANCE:
      Distribution of canine leptospirosis cases in Oregon fit the rainfall theory
      pattern. Dermatologic conditions were present in 9 of 64 (14%) dogs that had a
      diagnosis of leptospirosis; however, further investigation is needed to determine
      whether such conditions predispose dogs to the disease.

PMID- 27031418
TI  - Laparoscopic-assisted splenectomy in dogs: 18 cases (2012-2014).
AB  - OBJECTIVE: To describe the operative technique and perioperative outcome for
      laparoscopic-assisted splenectomy (LAS) in dogs. DESIGN: Retrospective case
      series. ANIMALS: 18 client-owned dogs. PROCEDURES: Medical records of dogs with
      naturally occurring disease of the spleen treated by means of LAS between 2012
      and 2014 were reviewed. History, signalment, results of physical examination,
      results of preoperative diagnostic testing, details of surgical technique,
      intraoperative findings including results of abdominal exploration and staging,
      concurrent surgical procedures, complications, histopathologic diagnoses,
      duration of postoperative hospitalization, and perioperative outcome were
      recorded. The perioperative period was defined as the time from hospital
      admission for LAS until discharge or death (within the same visit). RESULTS: All
      dogs underwent initial abdominal exploration and staging via multiple 5-mm
      laparoscopic ports (n = 2) or a single commercially available multichannel port
      (16), followed by minilaparotomy with insertion of a wound retraction device,
      progressive exteriorization of the spleen, sealing of hilar vessels, and
      splenectomy. Splenectomy was performed for treatment of a splenic mass (n = 15),
      suspected neoplasia (2), or refractory immune-mediated disease (1). Median size
      (width * length) of splenic masses was 5 * 5 cm (range, 1.6 to 11.0 cm * 1.5 to
      14.5 cm). Complications were limited to minor intraoperative hemorrhage in 1 dog;
      no patient required conversion to open laparotomy. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that LAS was technically feasible in dogs and not
      associated with major complications. Further evaluation is required; however, in
      appropriately selected patients, LAS may offer the benefits of a minimally
      invasive technique, including a smaller incision and improved illumination and
      magnification during exploration and staging.

PMID- 27031419
TI  - Evaluation and comparison of xylazine hydrochloride and dexmedetomidine
      hydrochloride for the induction of emesis in cats: 47 cases (2007-2013).
AB  - OBJECTIVE: To evaluate and compare i.m. administration of xylazine hydrochloride
      and dexmedetomidine hydrochloride for the induction of emesis in cats. DESIGN:
      Retrospective case series. ANIMALS: 47 cats with a history of suspected ingestion
      of a toxic substance or foreign material between June 2007 and June 2013.
      PROCEDURES: Data collected for analysis from the medical records included
      signalment, drug dose and route of administration, whether a repeated dose of the
      emetic agent was administered, and outcome (emesis, yes or no). RESULTS: Cats in
      the 2 treatment groups did not differ with regard to age, sex, or breed
      distribution. The range of doses of xylazine administered i.m. was 0.36 to 0.64
      mg/kg (0.16 to 0.29 mg/lb). The range of doses of dexmedetomidine administered
      i.m. was 6 to 18 MUg/kg (2.7 to 8.2 MUg/lb). A repeated dose of xylazine or
      dexmedetomidine was given to 3 and 1 cats, respectively. Emesis was successfully
      induced in 24 of the 47 (51.1%) cats. Nine of the 21 (43%) cats that received
      xylazine vomited and 15 of the 26 (58%) cats that received dexmedetomidine
      vomited. Percentage of cats that vomited after either drug administration did not
      differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Following i.m.
      administration in cats, xylazine and dexmedetomidine were similarly effective for
      induction of emesis, indicating that dexmedetomidine is a comparable alternative
      to xylazine for this purpose. Prospective studies are needed to determine the
      optimal i.m. dose of dexmedetomidine for induction of emesis in cats.

PMID- 27031420
TI  - Use of a frameless computed tomography-guided stereotactic biopsy system for
      nasal biopsy in five dogs.
AB  - CASE DESCRIPTION: 5 dogs (median age, 9 years; median body weight, 31 kg [68.2
      lb]) with undefined nasal masses were examined after undergoing CT of the head
      and nasal biopsy via a rostral rhinoscopic or unaided (blind) approach because
      histologic results for collected biopsy specimens (inflammatory, necrotic, or
      hemorrhagic disease) suggested the specimens were nonrepresentative of the
      underlying disease process identified via CT (aggressive or malignant disease).
      CLINICAL FINDINGS: Clinical signs at the time dogs were evaluated included open
      mouth breathing, sneezing, or unilateral epistaxis. Histologic findings
      pertaining to the original biopsy specimens were suggestive of benign processes
      such as inflammation. In an attempt to obtain better representative specimens, a
      frameless CT-guided stereotactic biopsy system (CTSBS) was used to collect
      additional biopsy specimens from masses within the nasal and sinus passages of
      the dogs. The second set of biopsy specimens was histologically evaluated.
      TREATMENT AND OUTCOME: Histologic evaluation of biopsy specimens collected via
      the CTSBS revealed results suggestive of malignant neoplasia (specifically,
      chondrosarcoma, hemangiopericytoma, or undifferentiated sarcoma) for 3 dogs, mild
      mixed-cell inflammation for 1 dog, and hamartoma for 1 dog. No complications were
      reported. These findings resulted in a change in treatment recommendations for 3
      dogs and confirmed that no additional treatment was required for 1 dog (with
      hamartoma). For the remaining dog, in which CT findings and clinical history were
      strongly suggestive of neoplasia, the final diagnosis was rhinitis. CLINICAL
      RELEVANCE: Biopsy specimens were safely collected from masses within the nasal
      and sinus passages of dogs by use of a frameless CTSBS, allowing a definitive
      diagnosis that was unachievable with other biopsy approaches.

PMID- 27031421
TI  - Evaluation of serum amyloid A and haptoglobin concentrations as prognostic
      indicators for horses with colic.
AB  - OBJECTIVE: To evaluate the use of the acute-phase proteins serum amyloid A (SAA)
      and haptoglobin as prognostic indicators in horses with colic with regard to the
      need for surgical intervention, development of complications, and hospitalization
      cost and duration. DESIGN: Prospective observational study. ANIMALS: 20
      clinically normal horses and 42 horses with colic. PROCEDURES: Total WBC and
      neutrophil counts and plasma fibrinogen, SAA, and haptoglobin concentrations were
      compared between healthy (control) horses and horses admitted to a veterinary
      teaching hospital for colic. Clinicopathologic values were compared between
      medical and surgical colic cases to test the ability of acute-phase proteins to
      predict indication for surgical intervention, development of complications, and
      duration and cost of hospitalization. RESULTS: Mean SAA concentration was
      significantly higher in the surgical group, compared with that for both the
      control and medical groups. Haptoglobin concentration did not differ
      significantly among groups. Horses with colic and an abnormally increased SAA
      concentration (> 5 MUg/mL) were more likely to be managed surgically than
      medically (OR, 5.7; 95% confidence interval, 1.4 to 22.8). Horses with small
      intestinal lesions had significantly higher SAA concentrations than did control
      horses. Euthanasia due to a poor prognosis or the development of thrombophlebitis
      was more likely for horses with an SAA concentration > 5 MUg/mL (OR, 7.6; 95%
      confidence interval, 1.1 to 52.4). A weak positive correlation (r = 0.30) was
      observed between cost of treatment and SAA concentration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Horses with colic that had an abnormally increased SAA
      concentration were more likely to require surgical intervention, develop
      thrombophlebitis, or be euthanized because of a poor prognosis despite treatment.

PMID- 27031422
TI  - Mitogen-activated protein kinase phosphatase-1: function and regulation in bone
      and related tissues.
AB  - In this review, we have highlighted work that has clearly demonstrated that
      mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a negative
      regulator of MAPKs, is an important signaling mediator in bone, muscle, and fat
      tissue homeostasis and differentiation. Further, we examined recent studies with
      particular focus on MKP-1 overexpression or deletion and its impact on tissues
      connected to bone. We also summarized regulation of MKP-1 by known skeletal
      regulators like parathyroid hormone (PTH)/PTH-related peptide (PTHrP) and bone
      morphogenic proteins. MKP-1's integration into the pathophysiological state of
      osteoporosis, osteoarthritis, rheumatoid arthritis, obesity, and muscular
      dystrophy are examined to emphasize possible involvement of MKP-1 both at the
      molecular level and in disease complications such as sarcopenia- or diabetes
      related osteoporosis. We predict that understanding the mechanism of MKP-1
      mediated signaling in bone-muscle-fat crosstalk will be a key in coordinating
      their activities and developing therapeutics to improve clinical outcomes for
      diseases associated with advanced age. 

PMID- 27031423
TI  - Maize cytokinin dehydrogenase isozymes are localized predominantly to the
      vacuoles.
AB  - The maize genome encompasses 13 genes encoding for cytokinin dehydrogenase
      isozymes (CKXs). These enzymes are responsible for irreversible degradation of
      cytokinin plant hormones and thus, contribute regulating their levels. Here, we
      focus on the unique aspect of CKXs: their diverse subcellular distribution,
      important in regulating cytokinin homeostasis. Maize CKXs were tagged with green
      fluorescent protein (GFP) and transiently expressed in maize protoplasts. Most of
      the isoforms, namely ZmCKX1, ZmCKX2, ZmCKX4a, ZmCKX5, ZmCKX6, ZmCKX8, ZmCKX9, and
      ZmCKX12, were associated with endoplasmic reticulum (ER) several hours after
      transformation. GFP-fused CKXs were observed to accumulate in putative
      prevacuolar compartments. To gain more information about the spatiotemporal
      localization of the above isoforms, we prepared stable expression lines of all
      ZmCKX-GFP fusions in Arabidopsis thaliana Ler suspension culture. All the ER
      associated isoforms except ZmCKX1 and ZmCKX9 were found to be targeted primarily
      to vacuoles, suggesting that ER-localization is a transition point in the
      intracellular secretory pathway and vacuoles serve as these isoforms' final
      destination. ZmCKX9 showed an ER-like localization pattern similar to those
      observed in the transient maize assay. Apoplastic localization of ZmCKX1 was
      further confirmed and ZmCKX10 showed cytosolic/nuclear localization due to the
      absence of the signal peptide sequence as previously reported. Additionally, we
      prepared GFP-fused N-terminal signal deletion mutants of ZmCKX2 and ZmCKX9 and
      clearly demonstrated that the localization pattern of these mutant forms was
      cytosolic/nuclear. This study provides the first complex model for spatiotemporal
      localization of the key enzymes of the cytokinin degradation/catabolism in
      monocotyledonous plants. 

PMID- 27031425
TI  - Barley (Hordeum distichon L.) roots synthesise volatile aldehydes with a strong
      age-dependent pattern and release (E)-non-2-enal and (E,Z)-nona-2,6-dienal after
      mechanical injury.
AB  - In the context of chemical ecology, the analysis of the temporal production
      pattern of volatile organic compounds (VOCs) in root tissues and the emission
      rate measurement of root-emitted VOCs are of major importance for setting up
      experiments to study the implication of these compounds in biotic interactions.
      Such analyses, however, remain challenging because of the belowground location of
      plant root systems. In this context, this study describes the evolution of the
      root VOC production pattern of barley (Hordeum distichon L.) at five
      developmental stages from germination to the end of tillering and evaluates the
      emission of the identified VOCs in an artificial soil. VOCs produced by crushed
      root tissues and released by unexcavated root systems were analysed using dynamic
      sampling devices coupled to a gas chromatography-mass spectrometry methodology
      (synchronous SCAN/SIM). The results showed that, at each analysed developmental
      stage, crushed barley roots produced mainly four volatile aldehydes: hexanal; (E)
      hex-2-enal; (E)-non-2-enal; and (E,Z)-nona-2,6-dienal. Higher total and
      individual VOC concentrations were measured in 3-day-old seminal roots compared
      with older phenological stages. For each developmental stage, the lipoxygenase
      (LOX) activity was greater for linoleic acid than alpha-linolenic acid and the
      greatest LOX activities using linoleic and alpha-linolenic acids as substrates
      were measured in 7- and 3-day-old roots, respectively. The analysis of VOCs
      released by barley roots into the soil showed that (E)-non-2-enal and (E,Z)-nona
      2,6-dienal were the only VOCs emitted in quantifiable amounts by mechanically
      injured roots. 

PMID- 27031424
TI  - Exogenous application of pectin-derived oligosaccharides to grape berries
      modifies anthocyanin accumulation, composition and gene expression.
AB  - Anthocyanins are secondary metabolites synthesized in grape berry skins via the
      phenylpropanoid pathway, with functions ranging from skin coloration to
      protection against pathogens or UV light. Accumulation of these compounds is
      highly variable depending on genetics, environmental factors and viticultural
      practices. Besides their biological functions, anthocyanins improve wine quality,
      as a high anthocyanin content in berries has a positive impact on the color,
      total phenolic concentration and, ultimately, the price of wine. The present work
      studies the effect of the pre-veraison application of pectin derived
      oligosaccharides (PDO) on the synthesis and accumulation of these compounds, and
      associates the changes observed with the expression of key genes in the
      phenylpropanoid pathways. To this end, pre-veraison Cabernet Sauvignon bunches
      were treated with PDO to subsequently determine total anthocyanin content, the
      anthocyanin profile (by HPLC-DAD) and gene expression (by qRT-PCR), using Ethrel
      and water treatments for comparison. The results show that PDO were as efficient
      as Ethrel in generating a significant rise in total anthocyanin content at 30
      days after treatment (dat), compared with water treatments (1.32, 1.48 and 1.02
      mg e.Mv-3G/g FW respectively) without any undesirable effect on berry size,
      soluble solids, tartaric acid concentration or pH. In addition, a significant
      alteration in the anthocyanin profile was observed. Specifically, a significant
      increase in the relative concentration of malvidin was observed for both PDO and
      Ethrel treatments, compared with water controls (52.8; 55.0 and 48.3%,
      respectively), with a significant rise in tri-hydroxylated forms and a fall in di
      hydroxylated anthocyanins. The results of gene expression analyses suggest that
      the increment in total anthocyanin content is related to a short term increase in
      phenylalanine ammonia-lyase (PAL) expression, mediated by a decrease in MYB4A
      expression. A longer term increase in UDP-glucose flavonoid 3-O
      glucosyltransferase (UFGT) expression, probably mediated by a rise in MYBA1 was
      also observed. Regarding the anthocyanin profile, despite the increase observed
      in MYB5A expression in PDO and Ethrel treatments, no changes in flavonoid 3'
      hydroxylase (F-3'-H); flavonoid 3'5'-hydroxylase (F-3'5'-H) or O
      methyltransferase (OMT) could be related with the profile modifications
      described. Overall, this study highlights that application of PDO is a novel
      means of altering specific grape berry anthocyanins, and could be a means of
      positively influencing wine quality without the addition of agrochemicals. 

PMID- 27031426
TI  - Blue light alters miR167 expression and microRNA-targeted auxin response factor
      genes in Arabidopsis thaliana plants.
AB  - The effect of blue LED (450 nm) on the photomorphogenesis of Arabidopsis thaliana
      Col-0 plants and the transcript levels of several genes, including miRNAs,
      photoreceptors and auxin response factors (ARF) was investigated. It was observed
      that blue light accelerated the generative development, reduced the rosette leaf
      number, significantly reduced the leaf area, dry biomass and led to the
      disruption of conductive tissue formation. The blue LED differentially influenced
      the transcript levels of several phytochromes (PHY a, b, c, d, and e),
      cryptochromes (CRY 1 and 2) and phototropins (PHOT 1 and 2). At the same time,
      the blue LED significantly increased miR167 expression compared to a fluorescent
      lamp or white LEDs. This increase likely resulted in the enhanced transcription
      of the auxin response factor genes ARF4 and ARF8, which are regulated by this
      miRNA. These findings support the hypothesis that the effects of blue light on A.
      thaliana are mediated by auxin signalling pathway involving miRNA-dependent
      regulation of ARF gene expression. 

PMID- 27031427
TI  - Regulation of Arabidopsis thaliana plasma membrane glucose-responsive regulator
      (AtPGR) expression by A. thaliana storekeeper-like transcription factor, AtSTKL,
      modulates glucose response in Arabidopsis.
AB  - Biochemical, genetic, physiological, and molecular research in plants has
      demonstrated a central role of glucose (Glc) in the control of plant growth,
      metabolism, and development, and has revealed networks that integrate light,
      stresses, nutrients, and hormone signaling. Previous studies have reported that
      AtPGR protein as potential candidates for Glc signaling protein. In the present
      study, we characterized transcription factors that bind to the upstream region of
      the AtPGR gene isolated using the yeast one-hybrid screening with an Arabidopsis
      cDNA library. One of the selected genes (AtSTKL) appeared to confer elevated
      sensitivity to Glc response. Overexpression of AtSTKLs (AtSTKL1 and AtSTKL2)
      increased the sensitivity to Glc during the post-germination stages. In contrast,
      atstkl1 and atstkl2 antisense lines displayed reduced sensitivity to high Glc
      concentration during the early seedling stage. Furthermore, we showed that the
      two AtSTKLs bind to the 5'-GCCT-3' element of the upstream promoter region of the
      AtPGR gene in vitro and repress the beta-glucuronidase (GUS) activity in AtPGR
      promoter-GUS (P999-GUS) transgenic plants. Green fluorescent protein (GFP)-tagged
      AtSTKLs were localized in the nuclei of transgenic Arabidopsis cells.
      Collectively, these results suggest that AtSTKL1 and AtSTKL2 function both as
      repressors of AtPGR transcription and as novel transcription factors in the Glc
      signaling pathway. 

PMID- 27031428
TI  - Chitin and carbon nanotube composites as biocompatible scaffolds for neuron
      growth.
AB  - The design of biocompatible implants for neuron repair/regeneration ideally
      requires high cell adhesion as well as good electrical conductivity. Here, we
      have shown that plasma-treated chitin carbon nanotube composite scaffolds show
      very good neuron adhesion as well as support of synaptic function of neurons. The
      addition of carbon nanotubes to a chitin biopolymer improved the electrical
      conductivity and the assisted oxygen plasma treatment introduced more oxygen
      species onto the chitin nanotube scaffold surface. Neuron viability experiments
      showed excellent neuron attachment onto plasma-treated chitin nanotube composite
      scaffolds. The support of synaptic function was evident on chitin/nanotube
      composites, as confirmed by PSD-95 staining. The biocompatible and electrically
      conducting chitin nanotube composite scaffold prepared in this study can be used
      for in vitro tissue engineering of neurons and, potentially, as an implantable
      electrode for stimulation and repair of neurons. 

PMID- 27031429
TI  - Re: Enteral Nutrition Intolerance in Critically Ill Septic Burn Patients.

PMID- 27031430
TI  - Pediatric Burns from Glass-Fronted Fireplaces in Canada: A Growing Issue Over the
      Past 20 Years.
AB  - There is an alarming lack of public awareness surrounding the safety of glass
      fronted fireplaces. This has resulted in an active campaign from the American
      Burn Association Prevention Committee. One issue encountered while advocating for
      prevention among manufacturers is the lack of corroborating and accurate data.
      The purpose of this study was to examine the annual trends and epidemiology of
      glass-fronted fireplace-related burn injuries to children less than 15 years old,
      who presented to Canadian emergency departments between 1990 and 2010. Records of
      pediatric burn injuries related to glass-fronted fireplaces were extracted from
      the Canadian Hospitals Injury Reporting and Prevention Program database for the
      study period (1990-2010). Cases were analyzed in terms of anatomic area affected,
      demographics, seasonality, safety device use, and injury severity. A total of 616
      cases of burns from glass-fronted fireplaces were identified. The incidence
      increased at an average of 2.7 cases per year. This is a greater than 20-fold
      increase over 20 years. Seventy-five percentage of the cases occurred in children
      less than 2 years, and 95% occurred in children less than 5 years. The study
      demonstrated a growing risk from glass-fronted fireplace burns, likely due to the
      increasing popularity of household gas fireplace units. These units are a
      particular risk to children less than 2 years, attributable to their developing
      mobility and reduced reaction time. This is a preventable injury that should be
      addressed through changes to legislation and manufacturing.

PMID- 27031431
TI  - Methyl Iodide Exposure Presenting as Severe Chemical Burn Injury with
      Neurological Complications and Prolonged Respiratory Insufficiency.
AB  - Methyl iodide (iodomethane) is a monohalomethane that is mainly used as an
      intermediate in the manufacturing of different pharmaceuticals and pesticides.
      Until now, only 13 cases of methyl iodide poisoning have been described in the
      literature. The authors present the first case of severe chemical burn injury due
      to methyl iodide exposure in a 36-year-old Caucasian man who suffered superficial
      to partial-thickness burn injuries over 75% of his BSA and developed neurological
      malfunctions and prolonged respiratory insufficiency. Human poisoning with methyl
      iodide is very rare. In addition to the already described neurological symptoms
      and respiratory insufficiency, severe chemical burn injury can cause a life
      threatening medical emergency.

PMID- 27031432
TI  - The Need for a Uniform Deceased Donor Allograft Sharing Guideline.

PMID- 27031433
TI  - Are the Governments Listening? Barriers to Transferring Patients Across State
      Lines During Mass Casualty Events Is a Real Unaddressed Threat.

PMID- 27031434
TI  - Survey of Attitudes to Self-Harm Patients Within a Burns and Plastic Surgery
      Department.
AB  - This study aims to build on the small body of evidence in previously published
      study exploring professional attitudes toward deliberate self-harm (DSH) patients
      from a predominantly burns and plastic surgery perspective. The authors
      distributed a short paper-based questionnaire within the burns and plastics
      department at the Queen Elizabeth Hospital, Birmingham, where the authors
      gathered a mixture of qualitative and quantitative data surrounding this issue.
      Professionals generally agree that DSH patients require input from multiple
      services and that surgery is not always the best option. The most common
      frustration among healthcare professionals regarding the care of DSH patients
      includes inconsistencies in care, lack of training/understanding, and the need
      for a policy to guide and standardize treatment. Improving training in line with
      UK National Institute of Health and Care Excellence (NICE) guidance along with
      introducing guidelines for the care of DSH patients may help smooth out
      inconsistencies in care and reduce frustrations among staff members.

PMID- 27031435
TI  - Ketamine: An Effective Tool for Preventing Suicide in Burned Combat Veterans.

PMID- 27031436
TI  - Re: Utilizing GIS Technology to Improve Fire Prevention Activities in an Urban
      Fire Department.

PMID- 27031437
TI  - Tenascin-C promotes migration of hepatic stellate cells and production of type I
      collagen.
AB  - Tenascin-C (TN-C) is an extracellular matrix glycoprotein markedly upregulated
      during liver fibrosis. The study is performed to explore the role of TN-C during
      the growth and activation of hepatic stellate cells (HSCs). We found that TN-C
      was accumulated accompanying with the HSC activation. Our data on cell migration
      assay revealed that the rTN-C treatment enhanced HSC migration in a dose- and
      time-dependent manner, but did not influence their proliferation. HSCs
      transfected with pTARGET-TN-C overexpression vector displayed increased the type
      I collagen (Col I) production. TN-C overexpression enhanced the process of HSC
      activation through TGF-beta1 signaling. Moreover, the anti-alpha9beta1 integrin
      antibody treatment blocked the TN-C-driven Col I increase in rat HSCs.
      Collectively, TN-C had a positive role in activation of HSCs mediated by TGF
      beta1 and alpha9beta1 integrin, manifesting elevation of Col I production and
      promotion of cell migration. Our results provide a potential insight for the
      therapy of hepatic fibrosis. 

PMID- 27031438
TI  - Removal and speciation of mercury compounds in flue gas from a waste incinerator.
AB  - The management and control of mercury emissions from waste incinerators have
      become more significant, because waste incinerators are sinks to treat mercury
      containing consumer products. This study investigated the effects of mercury
      concentrations and waste incineration temperatures on mercury speciation using a
      lab-scale experimental instrument. The removal characteristics of different
      mercury species were also investigated using an apparatus to simulate the fabric
      filter with a thin layer of additives such as Ca(OH)2 and NaHCO3, activated
      carbon (AC), and fly ash. HgCl2 generation rates peaked at 800 degrees C for
      initial Hg(0) concentrations of 0.08-3.61 mg/Nm(3) in the presence of 400 ppm
      HCl. A linear relationship was established between the generation rate of HgCl2
      and the logarithmic value of initial mercury concentration. Fly ash proved highly
      efficient in mercury removal, being equal or superior to AC. On the other hand,
      Ca(OH)2 and NaHCO3 were shown to have no effects on mercury removal. In the dry
      scrubbing process, alkali agent is often sprayed in amounts beyond those
      stoichiometrically required to aid acidic gas removal. The research suggests,
      however, that this may hinder mercury removal from the flue gas of solid waste
      incinerators. 

PMID- 27031439
TI  - Quantifying the Effects of Expert Selection and Elicitation Design on Experts'
      Confidence in Their Judgments About Future Energy Technologies.
AB  - Expert elicitations are now frequently used to characterize uncertain future
      technology outcomes. However, their usefulness is limited, in part because:
      estimates across studies are not easily comparable; choices in survey design and
      expert selection may bias results; and overconfidence is a persistent problem. We
      provide quantitative evidence of how these choices affect experts' estimates. We
      standardize data from 16 elicitations, involving 169 experts, on the 2030 costs
      of five energy technologies: nuclear, biofuels, bioelectricity, solar, and carbon
      capture. We estimate determinants of experts' confidence using survey design,
      expert characteristics, and public R&D investment levels on which the elicited
      values are conditional. Our central finding is that when experts respond to
      elicitations in person (vs. online or mail) they ascribe lower confidence (larger
      uncertainty) to their estimates, but more optimistic assessments of best-case
      (10th percentile) outcomes. The effects of expert affiliation and country of
      residence vary by technology, but in general: academics and public-sector experts
      express lower confidence than private-sector experts; and E.U. experts are more
      confident than U.S. experts. Finally, extending previous technology-specific
      work, higher R&D spending increases experts' uncertainty rather than resolves it.
      We discuss ways in which these findings should be seriously considered in
      interpreting the results of existing elicitations and in designing new ones.

PMID- 27031440
TI  - Clinical assessment of head orientation profile development and its relationship
      with positional plagiocephaly in healthy term infants - A prospective study.
AB  - BACKGROUND: Positional plagiocephaly refers to atypical development of an uneven
      head shape with asymmetrical head orientation as a post-natal risk factor. The
      development of the head orientation profile and its relationship with positional
      plagiocephaly are lacking. OBJECTIVES: To explore the head orientation profile
      development and its relationship with positional plagiocephaly in healthy full
      term infants. METHODS: A prospective observational study including 94 infants was
      conducted. Head orientation measures including head orientation duration, head
      orientation strength and latency to turn were conducted at three, six and nine
      weeks of age. Plagiocephaly outcome was measured by modified Cranial Vault
      Asymmetry Index at nine weeks. RESULTS: Lateral head orientation duration
      predominated at three weeks, mean (standard deviation) (right=40 [21.7]%; left=41
      [21.5]%; midline=19 [19.9]%). It decreased bilaterally in favour of midline
      positioning at nine weeks (right=30 [22.3]%; left=24 [22.0]%; midline=46 [27]%.
      Although head orientation strength was similar across the three ages after
      accounting for side, head orientation strength to left was decreased from three
      to nine weeks (p=0.031; 95% CI: 0.12-2.06). There was a reduction in left
      consistent with increase in left-bias from 3weeks to 6weeks of age (p=0.011).
      Positional plagiocephaly at nine weeks was associated with head orientation
      duration-right (p<0.001; r(2)=0.20); head orientation duration-left (p<0.001;
      r(2)=0.17); head orientation strength at three and six weeks (p<0.001;
      r(2)=0.22), but not latency to turn. CONCLUSIONS: Healthy infants show
      progressive change from symmetrical lateral head orientation to midline
      orientation from three to nine weeks. There is association of head orientation
      duration and strength with positional plagiocephaly.

PMID- 27031441
TI  - Reconstitution of ST2 (IL-1R4) specific for IL-33 activity; no suppression by IL
      1Ra though a common chain IL-1R3 (IL-1RAcP) shared with IL-1.
AB  - Interleukin-33 (IL-33) receptors are composed of ST2 (also known as IL-1R4), a
      ligand binding chain, and IL-1 receptor accessory protein (IL-1RAcP, also known
      as IL-1R3), a signal transducing chain. IL-1R3 is a common receptor for IL
      1alpha, and IL-1beta, IL-33, and three IL-36 isoforms. A549 human lung epithelial
      cells are highly sensitive to IL-1alpha and IL-1beta but not respond to IL-33.
      The lack of responsiveness to IL-33 is due to ST2 expression. ST2 was stably
      transfected into A549 cells to reconstitute its activity. RT-PCR and FACS
      analysis confirmed ST2 expression on the cell surface of A549/ST2 cells. Upon IL
      33 stimulation, A549/ST2 cells induced IL-8 and IL-6 production in a dose
      dependent manner while A549/mock cells remained unresponsive. There was no
      difference in IL-1alpha and IL-1beta activity in A549/ST2 cells compared to
      A549/mock cells despite the fact that IL-33 shares IL-1R3 with IL-1alpha/beta. IL
      33 activated inflammatory signaling molecules in a time- and dose-dependent
      manner. Anti-ST2 antibody and soluble recombinant ST2-Fc abolished IL-33-induced
      IL-6 and IL-8 production in A549/ST2 cells but the IL-1 receptor antagonist
      failed to block IL-33-induced cytokines. This result demonstrates for the first
      time the reconstitution of ST2 in A549 human lung epithelial cell line and
      verified its function in IL-33-mediated cytokine production and signal
      transduction.

PMID- 27031442
TI  - Recruitment of CD16(+) monocytes to endothelial cells in response to LPS
      treatment and concomitant TNF release is regulated by CX3CR1 and interfered by
      soluble fractalkine.
AB  - Fractalkine (FKN, CX3CL1) is a regulator of leukocyte recruitment and adhesion,
      and controls leukocyte migration on endothelial cells (ECs). We show that FKN
      triggers different effects in CD16(+) and CD16(-) monocytes, the two major
      subsets of human monocytes. In the presence of ECs a lipopolysaccharide (LPS)
      stimulus led to a significant increase in tumor necrosis factor (TNF)-secretion
      by CD16(+) monocytes, which depends on the interaction of CX3CR1 expressed on
      CD16(+) monocytes with endothelial FKN. Soluble FKN that was efficiently shed
      from the surface of LPS-activated ECs in response to binding of CD16(+) monocytes
      to ECs, diminished monocyte adhesion in down-regulating CX3CR1 expression on the
      surface of CD16(+) monocytes resulting in decreased TNF-secretion. In this
      process the TNF-converting enzyme (TACE) acts as a central player regulating FKN
      shedding and TNFalpha-release through CD16(+) monocytes interacting with ECs.
      Thus, the release and local accumulation of sFKN represents a mechanism that
      limits the inflammatory potential of CD16(+) monocytes by impairing their
      interaction with ECs during the initial phase of an immune response to LPS. This
      regulatory process represents a potential target for therapeutic approaches to
      modulate the inflammatory response to bacterial components.

PMID- 27031443
TI  - Alarmin human alpha defensin HNP1 activates plasmacytoid dendritic cells by
      triggering NF-kappaB and IRF1 signaling pathways.
AB  - Human neutrophil peptide 1 (HNP1), a predominant alpha defensin in the
      azurophilic granules of human neutrophils, is an alarmin capable of inducing the
      migration and maturation of human myeloid/conventional dendritic cells. However,
      it is not determined whether it can activate plasmacytoid dendritic cells (pDCs).
      Herein, we found that both human pDCs and CAL-1 cells, a pDC-like cell line,
      produced IFNalpha upon treatment with HNP1. Additionally, HNP1 could promote CpG
      ODN-induced pDC production of proinflammatory cytokines including IFNalpha. HNP1
      triggered activation of NF-kappaB and nuclear translocation of interferon
      regulatory factor 1 (IRF1) in CAL-1 cells. HNP1 upregulation of cytokine
      expression in pDCs was inhibited by blockade of NF-kappaB activation or knockdown
      of IRF1, demonstrating the importance of these two signaling events in HNP1
      induced pDC activation. Using a human pDC-nude mouse model, HNP1 was shown to
      induce IFNalpha production by human pDCs in vivo. Thus, HNP1 can activate human
      pDCs using NF-kappaB and IRF signaling pathways, and HNP-induced IFN production
      may participate in the inflammatory pathogenesis in certain authoimmune diseases
      such as rheumatoid arthritis.

PMID- 27031444
TI  - Gender nonconforming and transgender children/youth: Family, community, and
      implications for practice.
AB  - PURPOSE: The aim of this article is to provide foundational knowledge on gender
      nonconforming/transgender children/youth. With this knowledge, providers'
      confidence and ability to address the needs of patients/families can increase.
      DATA SOURCES: Academic Search Premier, Cinahl, PubMed, World Professional
      Association for Transgender Health. CONCLUSIONS: The number of gender
      nonconforming/transgender children/youth presenting to healthcare providers is
      increasing. The situation presents a myriad of challenges to families. The
      identity trajectory of gender nonconforming children is variable, and watchful
      waiting while providing support to the child and family is advised. If gender
      dysphoria persists as puberty approaches, treatment with puberty blockers is
      recommended. This provides youth time to further explore their identity, while
      alleviating the distress of developing unwanted secondary natal sex
      characteristics. For these individuals, cross-sex hormones may be started at age
      16. IMPLICATIONS FOR PRACTICE: The complexities of providing care to gender
      nonconforming children/youth and their families are best met through an
      interdisciplinary approach. Consultation with and/or referral to specialists
      knowledgeable about transgender health care is advised. Beyond a basic
      understanding of gender nonconformance, of primary importance to
      patients/families is being heard and supported by their providers. Establishing a
      safe and welcome environment is paramount. Resources are provided.

PMID- 27031445
TI  - Discrepant mutational status between naevi and melanomas in naevus-associated
      melanomas: about mutation-specific immunohistochemistry.

PMID- 27031446
TI  - Surfactant assisted control on optical, fluorescence and phonon lifetime in alpha
      Bi2O3 microrods.
AB  - We report preparation of pure and surfactant added alpha-Bi2O3 microrods through
      simple chemical method at moderate temperature. Cetyltrimethyl ammonium bromide
      (CTAB) is used as a surfactant. X-ray diffraction (XRD), scanning electron
      microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, Raman
      spectroscopy, UV-Vis absorption and photoluminescence (PL) measurements were
      carried out to understand the effect of surfactant (CTAB) on structural, phonon
      and optical properties of the prepared material. It is observed that the
      crystallite size, optical band gap and the structural defects (oxygen vacancies)
      decreases due to the effect of surfactant. Raman spectral studies exhibit various
      phonon modes of Bi2O3 and also decrease in the FWHM of the phonon modes is
      observed after the addition of CTAB. 

PMID- 27031447
TI  - MDL and RMSEP assessment of spectral pretreatments by adding different noises in
      calibration/validation datasets.
AB  - In multivariate calibration, the optimization of pretreatment methods is usually
      according to the prediction error and there is a lack of robustness evaluation.
      This study investigated the robustness of pretreatment methods by adding
      different simulate noises to validation dataset, calibration and validation
      datasets, respectively. The root mean squared error of prediction (RMSEP) and
      multivariate detection limits (MDL) were simultaneously calculated to assess the
      robustness of different pretreatment methods. The result with two different near
      infrared (NIR) datasets illustrated that Multiplicative Scatter Correction (MSC)
      and Standard normal variate (SNV) were substantially more robust to additive
      noise with smaller REMSP and MDL value. 

PMID- 27031448
TI  - Reagent-Free Synthesis and Plasmonic Antioxidation of Unique Nanostructured Metal
      Metal Oxide Core-Shell Microfibers.
AB  - A photoresponsive inorganic microfiber with a plasmonic core-shell structure
      responds to visible light to achieve self-protection against oxidation in an open
      environment. The microfibers are synthesized via a newly developed reagent-free
      electrolytic method and have unique interfacial structures and high surface
      activity. 

PMID- 27031449
TI  - Asymptomatic falciparum malaria and genetic polymorphisms of Pfcrt K76T and
      Pfmdr1 N86Y among almajirai in northeast Nigeria.
AB  - INTRODUCTION: Malaria remains a public health challenge, especially in sub
      Saharan Africa where asymptomatic malaria is not uncommon. In the present study,
      the prevalence of asymptomatic falciparum malaria was investigated in almajirai,
      and the genetic polymorphisms of chloroquine (CQ) resistance biomarkers were
      assessed. METHODOLOGY: A total of 440 apparently healthy almajirai between 3 and
      12 years of age were randomly enrolled in Maiduguri, northeast Nigeria, between
      July and December 2010. Parasitemia and gametocytemia were assessed by light
      microscopy, and polymorphisms of Pfcrt K76T and Pfmdr1 N86Y were detected by
      nested polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP) techniques. RESULTS: The mean age of the subjects was 8.3 +/-
      4.5 years, with subjects <= 5 years accounting for 10.7% (47/440) of the
      population. Prevalence of asymptomatic falciparum parasitemia and gametocytemia
      were 12.7% (56/440) and 8.6% (38/440), respectively. Geometric mean parasite
      density (GMPD) was 240 (160-630) parasites/uL, while geometric mean gametocyte
      density (GMGD) was 53 (24-96) gametocytes/uL. The GMPD was higher among subjects
      <= 5 years of age (p = 0.027). Pfcrt 76T was detected in 5.4% (3/56) of the
      isolates, and no isolates harbored Pfmdr1 86Y mutant. CONCLUSIONS: The study
      reveals asymptomatic falciparum malaria in almajirai and low levels of Pfcrt 76T
      and Pfmdr1 86Y alleles. These findings could hinder malaria control measures, and
      hence almajirai should be incorporated into malaria control programs.

PMID- 27031450
TI  - Zika virus: a new pandemic threat.
AB  - Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is
      related to dengue, Chikungunya, West Nile, yellow fever, and Japanese
      encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different
      species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are
      the vectors responsible for ZIKV infection in humans. It is also reported that
      ZIKV is transmitted congenitally, sexually, and through blood donation. Until
      recently, ZIKV outbreaks were sporadic and self-limiting. The first large
      epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika
      fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV
      epidemic which is rapidly spreading across the Americas. ZIKV infection remained
      relatively less studied in view of its low case numbers, and low clinical impact
      relative to other arboviruses. However, all this is set to change with its rapid
      spread in the Western hemisphere and suspected complications particularly
      microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to
      substantially add to both short-term and long-term economic burden of the
      effected countries. Due to the large number of people travelling across the
      borders and some reported cases of transmission of ZIKV via contaminated blood,
      screening and identification of asymptomatic infected individuals are important. 

PMID- 27031451
TI  - A retrospective study of risk factors for carbapenem-resistant Klebsiella
      pneumoniae acquisition among ICU patients.
AB  - INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly
      emerging as a life-threatening nosocomial infection. In this study, we aim to
      identify risk factors, especially antibiotic use, for CRKP infection among
      intensive care unit (ICU) patients. METHODOLOGY: This was a matched case-control
      study of a 67-bed ICU in a tertiary care teaching hospital from 1 January 2011
      through 30 June 2013. The control cases were selected among the patients with
      carbapenem-susceptible Klebsiella pneumoniae (CSKP) and were matched with CRKP
      cases for year of ICU admission and site of infection. The clinical outcomes and
      antibiotic treatments were analyzed. RESULTS: One hundred and thirty patients
      were included in the study (65 cases and 65 controls). Bivariable analysis showed
      that age of patients (p = 0.044), number of antibiotic groups (p = 0.001), and
      exposure to carbapenems (p < 0.001) were associated with CRKP infection. Using
      multivariate analysis adjusted for age, prior hospitalization, number of
      antibiotic groups, and previous exposure to carbapenems, previous carbapenem
      exposure (p < 0.001) was identified as an independent risk factor for CRKP
      infection. CONCLUSIONS: These data suggest that exposure to carbapenems is an
      independent risk factor for CRKP infection. Patients with this clinical factor
      should be targeted for interventions to reduce the subsequent risk of infection.

PMID- 27031452
TI  - Antimicrobial effect of probiotics on bacterial species from dental plaque.
AB  - INTRODUCTION: The antimicrobial role of probiotic Lactobacillus casei subspecies
      casei DG (L. casei DG) and of the mix culture of probiotic Lactobacillus
      acidophilus LA-5 and Bifidobacterium BB-12 was tested on species of
      Staphylococcus, Streptococcus, Pasteurella, and Neisseria genera from
      supragingival sites from dogs with dental disease of different breed, age, sex,
      weight, and diet. The research was conducted on these four genera because of
      their importance in zoonotic infections after dog bites. METHODOLOGY: Species
      from Staphylococcus, Streptococcus, Pasteurella, and Neisseria genera were
      isolated and identified. To test the antimicrobial efficacy of L. casei DG and
      the mixed culture of probiotic L. acidophilus LA-5 and Bifidobacterium bifidum BB
      12 on the pathogenic species, the agar overlay method was used. RESULTS: L. casei
      DG had a bactericidal effect on all analyzed species isolated from
      Staphylococcus, Streptococcus, Pasteurella, and Neisseria genera after 24 hours
      of incubation. The mixed probiotic culture made up of L. acidophilus LA-5 and
      Bifidobacterium BB-12 species had no bactericidal effect on the species of
      Staphylococcus and Streptococcus genera, which were resistant. However, it had a
      bacteriostatic effect on several species of Pasteurella and Neisseria genera.
      CONCLUSIONS: This work highlights the antimicrobial potential of probiotics in
      vitro, demonstrating that the probiotic L. casei DG has a bactericidal effect on
      all analyzed species isolated from dental plaque and that the mix culture of
      probiotic L. acidophilus LA-5 and Bifidobacterium BB-12 has only a bacteriostatic
      effect.

PMID- 27031453
TI  - Screening and genotyping of group B streptococcus in pregnant and non-pregnant
      women in Turkey.
AB  - INTRODUCTION: The purpose of this study was to investigate group B streptococcus
      (GBS) colonization, to compare the methods, to determine the relationship between
      GBS carriage and risk factors, and to genotype the GBS isolates. METHODOLOGY:
      Recto-vaginal swab specimens were obtained from 500 women, and a questionnaire
      was administered to each to assess their risk factors for GBS carriage. A
      culture, GBS antigen test, and polymerase chain reaction (PCR) were performed on
      all samples. Antibiotic susceptibility testing was performed, and the clonal
      relationship was determined by pulsed-field gel electrophoresis (PFGE) on all
      viable isolates. RESULTS: Of the 500 women, sixty-eight (13.6%) women were GBS
      carriers, of whom 9.8% were pregnant and 16.5% not. There was a significant
      difference between GBS carriage and history of premature rupture of membrane
      (PROM). GBS was isolated from 65 (13%) samples. GBS was positive in 70 (14%)
      samples by antigen test and in 62 (12.4%) by PCR. Sixty-eight of the 70 positive
      antigen tests were confirmed by PCR or culture. Fifty-five isolates were
      resistant to tetracycline, 16 to erythromycin and clindamycin, and 13 to
      levofloxacin. Thirteen different pulsotypes and 17 sporadic strains were
      determined by PFGE. CONCLUSIONS: GBS carriage rate in non-pregnant women was
      higher than in pregnant women. The GBS antigen test was more sensitive than
      culture and PCR. GBS isolates did not originate from a single clone and contained
      sporadic strains. There was a significant difference between GBS carriage and
      history of PROM. Epidemiologic data obtained in this study will help future
      studies.

PMID- 27031454
TI  - Role of Chlamydia pneumoniae in community-acquired pneumonia in hospitalized
      Jordanian adults.
AB  - INTRODUCTION: This study investigated the role of Chlamydia pneumoniae in the
      etiology of community-acquired pneumonia (CAP) in Jordanian adults. METHODOLOGY:
      Eighty hospitalized CAP patients and 110 healthy adults were enrolled. Overall
      prevalences of C. pneumoniae IgG antibodies in sera and the rate of acute
      infection were estimated, using the microimmunofluorescence method (MIF), at
      titers of 1:16 and 1:512, respectively. Moreover, a nested polymerase chain
      reaction (PCR) was used to detect C. pneumoniae DNA in nasopharyngeal and blood
      Buffy coat samples. RESULTS: Overall chlamydial IgG prevalence was higher in CAP
      cases than controls (70% versus 61.8%). Similarly, higher rate of acute infection
      was found in patients than in controls (16.3% versus 5.5%). By focusing on
      subjects testing positive at 1:16, acute infection was detectable in 23.2% of CAP
      cases, compared with 8.8% of seropositive controls. Chlamydial DNA was confirmed
      in 8.2% and 8.8% of nasopharyngeal specimens from controls and patients,
      respectively. Moreover, 10.9% and 7.5% of Buffy coats from controls and cases,
      respectively, were PCR-positive. When performances of both assays for detection
      of the pathogen were assessed, the sensitivities of MIF and PCR were low and
      comparable. However, MIF demonstrated higher specificity, positive predictive
      value, and negative predictive value than PCR. CONCLUSIONS: MIF-based data
      indicate that C. pneumoniae could be a potential causal agent of CAP in Jordan.
      This study may serve as a basis to elucidate the exact role C. pneumoniae and
      other co-infecting pathogens in the etiology of respiratory tract disease.

PMID- 27031455
TI  - Genotyping of Indian antigenic, vaccine, and field Brucella spp. using multilocus
      sequence typing.
AB  - INTRODUCTION: Brucellosis is one of the most important zoonotic diseases that
      affects multiple livestock species and causes great economic losses. The highly
      conserved genomes of Brucella, with > 90% homology among species, makes it
      important to study the genetic diversity circulating in the country. METHODOLOGY:
      A total of 26 Brucella spp. (4 reference strains and 22 field isolates) and 1 B.
      melitensis draft genome sequence from India (B. melitensis Bm IND1) were included
      for sequence typing. The field isolates were identified by biochemical tests and
      confirmed by both conventional and quantitative polymerase chain reaction (qPCR)
      targeting bcsp 31Brucella genus-specific marker. Brucella speciation and
      biotyping was done by Bruce ladder, probe qPCR, and AMOS PCRs, respectively, and
      genotyping was done by multilocus sequence typing (MLST). RESULTS: The MLST
      typing of 27 Brucella spp. revealed five distinct sequence types (STs); the B.
      abortus S99 reference strain and 21 B. abortus field isolates belonged to ST1. On
      the other hand, the vaccine strain B. abortus S19 was genotyped as ST5.
      Similarly, B. melitensis 16M reference strain and one B. melitensis field isolate
      were grouped into ST7. Another B. melitensis field isolate belonged to ST8 (draft
      genome sequence from India), and only B. suis 1330 reference strain was found to
      be ST14. CONCLUSION: The sequences revealed genetic similarity of the Indian
      strains to the global reference and field strains. The study highlights the
      usefulness of MLST for typing of field isolates and validation of reference
      strains used for diagnosis and vaccination against brucellosis.

PMID- 27031456
TI  - Helicobacter pylori antibiotic susceptibility patterns in Bangladesh: Emerging
      levofloxacin resistance.
AB  - INTRODUCTION: The most recent study to report Helicobacter pylori antibiotic
      resistance rates in Bangladesh was published 15 years ago and did not include
      levofloxacin. We therefore aimed to determine the current antibiotic
      susceptibility of H. pylori to amoxicillin, clarithromycin, metronidazole,
      tetracycline and levofloxacin in Bangladesh. METHODOLOGY: This study included 133
      consecutive patients who underwent endoscopy examination at Dhaka Medical College
      in November 2014. The serial two-fold agar dilution method was used to determine
      the minimum inhibitory concentrations of the five antibiotics. RESULTS: Among 56
      cultured strains, H. pylori showed high rates of resistance to clarithromycin and
      metronidazole (39.3% and 94.6%, respectively). Moreover, levofloxacin showed an
      emerging antimicrobial resistance pattern (66.1%), which was higher in patients
      with gastritis than that in those with peptic ulcers (p = 0.02). The resistance
      rate of levofloxacin was significantly higher in patients living in Dhaka city
      compared to those living in the village (p = 0.049). However, amoxicillin and
      tetracycline resistance rates were very low. Resistance to both metronidazole and
      levofloxacin was most commonly observed. CONCLUSIONS: The rates of resistance to
      clarithromycin, metronidazole, and levofloxacin were high in Bangladesh, which
      suggests that triple therapy based on these drugs may not be useful as first-line
      therapies in Bangladesh. Alternative strategies such as furazolidone-based triple
      therapy, bismuth-based quadruple therapies, or sequential therapy may be more
      effective for patients in in Bangladesh.

PMID- 27031457
TI  - Healthcare-associated infections in a newly opened pediatric intensive care unit
      in Turkey: Results of four-year surveillance.
AB  - INTRODUCTION: Healthcare-associated infections (HAIs) are important causes of
      morbidity and mortality, especially in critically ill patients in intensive care
      units. The aim of this study was to assess the rate and distribution of HAIs,
      pathogens, and antimicrobial susceptibility patterns in a newly opened pediatric
      intensive care unit (PICU). METHODOLOGY: The infection control team detected and
      recorded HAI cases according to the Centers for Disease Control and Prevention's
      criteria in the PICU of Marmara University Pendik Training and Research Hospital
      over a four-year period following its opening. Laboratory-based HAIs surveillance
      was performed prospectively from 1 January 2011 to 30 November 2014. RESULTS:
      During the study period, 1,007 patients hospitalized in the PICU and 224 HAIs
      were identified. The overall HAI rate was 22.24%, and the incidence density was
      20.71 per 1,000 patient-days. The most commonly observed HAIs were bloodstream
      infection (35.7%), pneumonia (21.4%), and urinary tract infection (20.5%), and
      the three most common HAI pathogens were Klebsiella spp. (19.4%), Pseudomonas
      aeruginosa (13.8%), and Acinetobacter baumanii (12%). Methicillin resistance was
      detected in 78% of coagulase-negative Staphylococcus. Presence of extended
      spectrum beta-lactamases was determined in 45% and 54% of Klebsiella spp. strains
      and Escherichia coli isolates, respectively. CONCLUSIONS: Our rate of HAIs is
      higher than the mean rates reported in PICU studies from developed countries.
      Active surveillance studies of HAIs is an essential component of infection
      control, which may contribute to improving preventive strategies in developing
      countries.

PMID- 27031458
TI  - CD64 index on neutrophils can diagnose sepsis and predict 30-day survival in
      subjects after ventilator-associated pneumonia.
AB  - INTRODUCTION: Sepsis associated with ventilator-associated pneumonia (VAP) causes
      mortality in intensive care unit (ICU) patients. The time of diagnosis is
      crucial, and microbiological cultures take time. In this study, the diagnostic
      accuracy of CD64 index to predict VAP-induced sepsis and survival time in
      subjects requiring mechanical ventilation were evaluated and compared to
      conventional biomarkers and culturing methods. METHODOLOGY: A total of 32
      subjects with VAP were included. Sepsis after VAP was diagnosed in 25 (78.1%)
      patients according to clinical signs, radiographic examination, and samples of
      blood and trachea taken for culturing. Simultaneously with cultures, CD64 index
      on neutrophils, C-reactive protein (CRP), procalcitonin (PCT), and count of
      leucocytes and neutrophils were determined. RESULTS: Biomarker values were
      evaluated in both groups of subjects (with and without sepsis after VAP). The
      values of CD64 index and CRP were significantly higher in the sepsis group.
      Receiver operating characteristic (ROC) curve analysis revealed an area under
      curve (AUC) of 0.929 for CD64 index in differentiating subjects with VAP-induced
      sepsis from those without sepsis. The biomarkers CRP and PCT showed comparable
      results (AUC of 0.869 and 0.909, respectively). Blood cultures were positive in
      12 subjects, endotracheal aspirate in 19. CD64 index and isolation of pathogen
      with positive blood cultures or from endotracheal aspirate (positive in 24 cases)
      could predict survival time before application of more targeted antibiotic
      therapy. CONCLUSIONS: CD64 index may be used as a useful diagnostic tool to
      recognize VAP-induced sepsis; moreover, accompanied with an identified pathogen,
      can predict survival for ICU patients.

PMID- 27031459
TI  - Outbreak of diarrhea among preweaning alpacas (Vicugna pacos) in the southern
      Peruvian highland.
AB  - INTRODUCTION: Infections, particularly diarrheal infections, are a major cause of
      neonatal death in South American camelids. The aim of this study was to identify
      the pathogens that could have caused the recent diarrhea outbreak among the
      alpacas in Silli, Cusco, located in the southern Peruvian highland. METHODOLOGY:
      Spleen, kidney, and intestine tissue along with fecal and intestinal lavage
      samples were obtained from 50 one- to five-week-old alpacas and analyzed for the
      presence of parasites, bacteria, and viruses. RESULTS: Laboratory testing of the
      50 crias included in this study revealed that 80% were infected with Eimeria
      spp., 40% with coronavirus, 34% with E. coli, 32% with rotavirus, 22% with
      Clostridium spp., and 20% with Cryptosporidium spp. Of these 50 alpaca crias, 20
      presented with a single infection (19 positive for Eimeria spp. and 1 positive
      for rotavirus). Co-infections with up to four pathogens occurred in 60% of the
      samples. The significance of such infections is not clear, but it is noteworthy
      that the animals suffering from necrotic and/or hemorrhagic enteritis presented
      with quadruple infections. It is likely that co-infections increase the severity
      of the disease. CONCLUSIONS: These data show that multiple pathogens circulate
      among young alpaca crias and could be associated with diarrheal disease in these
      animals. The findings from this study warrant the provision of subsidies for
      future assessment of the potential economic impact of these infections on the
      productivity of the Peruvian alpaca industry.

PMID- 27031460
TI  - Serologic evidence of the exposure of small mammals to spotted-fever Rickettsia
      and Rickettsia bellii in Minas Gerais, Brazil.
AB  - INTRODUCTION: Sources of pathogenic Rickettsia in wildlife are largely unknown in
      Brazil. In this work, potential tick vectors and seroreactivity of small mammals
      against four spotted-fever group Rickettsia (R. rickettsii, R. parkeri, R.
      amblyommii and R. rhipicephali) and Rickettsia bellii from peri-urban areas of
      Uberlandia, a major town in Brazil, are described for the first time.
      METHODOLOGY: Small mammals were captured and blood samples collected. Ticks were
      collected from the surface of the host and the environment and posteriorly
      identified. Reactivity of small mammal sera to Rickettsia was tested by indirect
      immunofluorescence assay (IFA) using crude antigens from five Brazilian
      Rickettsia isolates. RESULTS: Information was obtained from 416 small mammals (48
      Marsupialia and 368 Rodentia). Forty-eight animals were parasitized and two tick
      species, Ixodes loricatus and Amblyomma dubitatum, were found on several host
      species, with a few tick-host relationships described for the first time. From
      the 416 tested sera, 70 reacted to at least one Rickettsia antigen (prevalence of
      16.8%) and from these, 19 (27.1%) reacted to two or more antigens. Seroprevalence
      was higher for marsupials (39.6%) than for rodents (13.8%). Marsupial and
      Rhipidomys spp. sera reacted mainly (highest seroprevalence and titers) to R.
      bellii, and that of Necromys lasiurus mainly to R. rickettsii. CONCLUSIONS:
      Although the serologic assays poorly discriminate between closely related spotted
      fever group Rickettsia, the observed small mammal seroreactivity suggests the
      circulation of Rickettsia in the peri-urban area of Uberlandia, albeit at low
      levels.

PMID- 27031461
TI  - Respiratory syncytial virus and human metapneumovirus in severe lower respiratory
      tract infections in children under two.
AB  - INTRODUCTION: Viruses are the most important causative agents of acute lower
      respiratory tract infections (ALRTIs), ranked as the second leading cause of
      death and the primary cause of hospitalization in children. Respiratory syncytial
      virus (RSV) and human metapneumovirus (hMPV) are among the commonest viral causes
      of severe ALRTI. In this study, we aimed to study the burden of both RSV and hMPV
      in causing severe ALRTI in children younger than two years of age admitted to the
      pediatric intensive care unit (PICU). METHODOLOGY: Nasopharyngeal swabs were
      collected from children admitted to the PICU with a diagnosis of community
      acquired ALRTI who were two years of age or younger. Real-time polymerase chain
      reaction (RT-PCR) was used to test for RSV and hMPV. RESULTS: A total of 127
      swabs were screened for RSV and hMPV, of which 49.6% were negative for RSV and
      hMPV, 46.4% were positive for RSV, and 3.9% were positive for hMPV. With respect
      to RSV, the mean age of cases (4.01 +/- 5.05) and the monthly distribution
      (mainly January) were the most important risk factors. There were no
      statistically significant differences between the RSV group and control group
      regarding duration of hospital stay, mechanical ventilation need or duration, and
      underlying chronic conditions. CONCLUSIONS: RSV is important viral cause of
      severe ALRTIs in children younger than two years of age during this study period;
      hMPV played a minor role.

PMID- 27031462
TI  - The combined-disk boronic acid test as an accurate strategy for the detection of
      KPC carbapenemase in Central America.
AB  - INTRODUCTION: Carbapenemase-producing Klebsiella pneumoniae (KPC) outbreaks may
      cause a huge economical burden on developing countries. Furthermore, KPC can be
      challenging to detect. We describe the laboratory strategy for the detection of
      KPC from 2011 to 2013 in a tertiary care hospital in Central America with
      approximately 1,000 beds. METHODOLOGY: A retrospective analysis of a clinical
      laboratory database was done to determine the pragmatic application of the
      combined-disk boronic acid test during a KPC outbreak in Panama. A total of 1,026
      Klebsiella pneumoniae isolates were found, of which 133 were positive for KPC.
      The strategy during two phases was described according to the test employed as a
      confirmatory test for KPC. After the K. pneumoniae isolates were detected by the
      VITEK 2 system, blaKPC polymerase chain reaction (PCR) and the combined-disk
      boronic acid test were employed as a confirmatory test during phase one. The
      combined-disk boronic acid test was employed as a confirmatory test for KPC
      during phase two. RESULTS: The sensitivity, specificity, positive predictive
      value, and negative predictive value of the boronic acid test were 100%, 97%,
      91%, and 100%, respectively, when blaKPC PCR was employed as a confirmatory test
      during the start of the outbreak. Afterwards, modified VITEK 2 system parameters
      resulted in 116 suspicious KPC samples and the boronic acid test confirmed 102
      isolates. CONCLUSIONS: The use of an automated bacterial identification system
      and the boronic acid test for the detection of KPC was an effective and low-cost
      strategy for a clinical laboratory in Panama during an outbreak.

PMID- 27031463
TI  - Lactococcus lactis spp lactis infection in infants with chronic diarrhea: two
      cases report and literature review in children.
AB  - Lactococcus lactis is a gram-positive, facultative anaerobic coccus that is
      occasionally isolated from human mucocutaneous surfaces such as the intestines.
      It is used in the dairy industry for milk acidification and is mostly
      nonpathogenic in immunocompetent humans, however a number of cases of infection
      with L. lactis have been reported in recent years. In this article, we describe
      two cases of infection due to L. lactis in patients with chronic diarrhea. The
      first case is a five-month-old boy who was operated on for volvulus on his first
      day of life and had ileostomy with subsequent diagnosis of chronic diarrhea and
      bacteremia due to L. Lactis. The second case is a six-month-old girl with the
      diagnosis of chronic diarrhea that developed after a catheter-related bloodstream
      infection. Both of the infections due to L. Lactis spp lactis were successfully
      treated with intravenous vancomycin therapy. Although Lactococcus species is
      mostly known as nonpathogenic, it should be kept in mind as a potential pathogen,
      especially in patients with gastrointestinal disorders. 

PMID- 27031464
TI  - An Economic Analysis of Strategies to Control Clostridium Difficile Transmission
      and Infection Using an Agent-Based Simulation Model.
AB  - BACKGROUND: A number of strategies exist to reduce Clostridium difficile (C.
      difficile) transmission. We conducted an economic evaluation of "bundling" these
      strategies together. METHODS: We constructed an agent-based computer simulation
      of nosocomial C. difficile transmission and infection in a hospital setting. This
      model included the following components: interactions between patients and health
      care workers; room contamination via C. difficile shedding; C. difficile hand
      carriage and removal via hand hygiene; patient acquisition of C. difficile via
      contact with contaminated rooms or health care workers; and patient antimicrobial
      use. Six interventions were introduced alone and "bundled" together: (a)
      aggressive C. difficile testing; (b) empiric isolation and treatment of
      symptomatic patients; (c) improved adherence to hand hygiene and (d) contact
      precautions; (e) improved use of soap and water for hand hygiene; and (f)
      improved environmental cleaning. Our analysis compared these interventions using
      values representing 3 different scenarios: (1) base-case (BASE) values that
      reflect typical hospital practice, (2) intervention (INT) values that represent
      implementation of hospital-wide efforts to reduce C. diff transmission, and (3)
      optimal (OPT) values representing the highest expected results from strong
      adherence to the interventions. Cost parameters for each intervention were
      obtained from published literature. We performed our analyses assuming low,
      normal, and high C. difficile importation prevalence and transmissibility of C.
      difficile. RESULTS: INT levels of the "bundled" intervention were cost-effective
      at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in all
      importation prevalence and transmissibility scenarios. OPT levels of intervention
      were cost-effective for normal and high importation prevalence and
      transmissibility scenarios. When analyzed separately, hand hygiene compliance,
      environmental decontamination, and empiric isolation and treatment were the
      interventions that had the greatest impact on both cost and effectiveness.
      CONCLUSIONS: A combination of available interventions to prevent CDI is likely to
      be cost-effective but the cost-effectiveness varies for different levels of
      intensity of the interventions depending on epidemiological conditions such as C.
      difficile importation prevalence and transmissibility.

PMID- 27031465
TI  - Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning
      are Impaired Twelve Years Preceding Diagnosis of Alzheimer's Dementia.
AB  - Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with
      cognitive impairments and cortical thinning, and begins in medial perirhinal
      cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction
      (e.g., semantic object memory impairments) may predate or accompany ERC (i.e.,
      episodic memory) dysfunction in the preclinical course of typical AD. We
      developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness)
      using common neuropsychological tests in 31 healthy individuals and 58 early AD
      patients. These formulae estimated the longitudinal courses of mPRC and ERC
      functioning in independent groups of 28 optimally healthy individuals who
      developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy
      individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC
      NC estimated mPRC and ERC functioning at the earliest observation, 12 years
      preceding diagnosis, and a significant decline 4 years preceding the AD
      diagnosis. These findings demonstrate that specific neuropsychological
      impairments occur early in the course of preclinical AD and that tasks measuring
      mPRC functioning may serve as additional, powerful markers of preclinical AD.

PMID- 27031466
TI  - Alcohol Consumption and Incident Dementia: Evidence from the Sydney Memory and
      Ageing Study.
AB  - Alcohol consumption is a potentially modifiable risk factor for dementia, but the
      literature is not completely consistent. This inconsistency may be partly due to
      an interaction with the apolipoprotein E (APOE) genotype, an established risk
      factor for Alzheimer's dementia. The aim of this study was to examine whether
      alcohol consumption is associated with incident dementia or decline in specific
      cognitive domains over 4 years, and if this effect is modified by APOEE4 status.
      Non-demented community dwelling older adults (70-90 years) from an ongoing
      longitudinal study were assessed for cognitive impairment in attention/processing
      speed, language, executive function, visuospatial ability, and memory. Incident
      dementia was diagnosed according to DSM-IV criteria. Compared to those who did
      not drink in the previous 12 months, neither low consumption (HR 0.64 95% CI 0.3
      1.4) or risky consumption (HR 0.58 95% CI 0.2-1.5) was associated with incident
      dementia. Carriers of the APOEE4 allele were more likely to develop dementia, but
      there was no significant interaction with alcohol consumption.

PMID- 27031467
TI  - Impact of Depressive Symptoms on Memory for Emotional Words in Mild Cognitive
      Impairment and Late-Life Depression.
AB  - BACKGROUND: Amnestic mild cognitive impairment (aMCI) and late-life depression
      (LLD) are associated with increased risk of Alzheimer's disease (AD). This is
      also true for aMCI with concomitant depressive symptoms (aMCI/D+), but few
      studies have investigated this syndrome. OBJECTIVES: We aimed to clarify the
      association between cognitive and depressive symptoms in individuals at risk for
      AD by examining episodic memory for emotional stimuli in aMCI, aMCI/D+, and LLD.
      METHODS: Participants were 34 patients with aMCI, 20 patients with aMCI/D+, 19
      patients with LLD, and 28 healthy elderly adults. In an implicit encoding task,
      participants rated the emotional valence of 12 positive, 12 negative, and 12
      neutral words. Immediately and 20 minutes later, participants recalled as many
      words as possible. They were also asked to identify previously presented words
      during a yes/no recognition trial. RESULTS: At immediate recall, aMCI
      participants displayed better recall of emotional words, particularly positive
      words. aMCI/D+ and control participants displayed better recall of positive and
      negative words compared to neutral words. LLD participants recalled more negative
      than neutral words. At delayed recall, emotional words were generally better
      remembered than neutral words by all groups. At recognition, all subjects
      responded more liberally to emotional than to neutral words. CONCLUSION: We find
      that the type of emotional information remembered by aMCI patients at immediate
      recall depends on the presence or absence of depressive symptoms. These findings
      contribute to identifying sources of heterogeneity in individuals at risk for AD,
      and suggest that the cognitive profile of aMCI/D+ is different from that of aMCI
      and LLD. Future studies should systematically consider the presence of depressive
      symptoms in elderly at-risk individuals.

PMID- 27031468
TI  - The Zebrafish Equivalent of Alzheimer's Disease-Associated PRESENILIN Isoform
      PS2V Regulates Inflammatory and Other Responses to Hypoxic Stress.
AB  - Dominant mutations in the PRESENILIN genes PSEN1 and PSEN2 cause familial
      Alzheimer's disease (fAD) that usually shows onset before 65 years of age. In
      contrast, genetic variation at the PSEN1 and PSEN2 loci does not appear to
      contribute to risk for the sporadic, late onset form of the disease (sAD),
      leading to doubts that these genes play a role in the majority of AD cases.
      However, a truncated isoform of PSEN2, PS2V, is upregulated in sAD brains and is
      induced by hypoxia and high cholesterol intake. PS2V can increase gamma-secretase
      activity and suppress the unfolded protein response (UPR), but detailed analysis
      of its function has been hindered by lack of a suitable, genetically manipulable
      animal model since mice and rats lack this PRESENILIN isoform. We recently showed
      that zebrafish possess an isoform, PS1IV, that is cognate to human PS2V. Using an
      antisense morpholino oligonucleotide, we can block specifically the induction of
      PS1IV that normally occurs under hypoxia. Here, we exploit this ability to
      identify gene regulatory networks that are modulated by PS1IV. When PS1IV is
      absent under hypoxia-like conditions, we observe changes in expression of genes
      controlling inflammation (particularly sAD-associated IL1B and CCR5), vascular
      development, the UPR, protein synthesis, calcium homeostasis, catecholamine
      biosynthesis, TOR signaling, and cell proliferation. Our results imply an
      important role for PS2V in sAD as a component of a pathological mechanism that
      includes hypoxia/oxidative stress and support investigation of the role of PS2V
      in other diseases, including schizophrenia, when these are implicated in the
      pathology.

PMID- 27031469
TI  - Detection of Striatal Amyloid Plaques with [18F]flutemetamol: Validation with
      Postmortem Histopathology.
AB  - Amyloid imaging is limited by an inconsistent relationship between cerebral
      cortex amyloid- beta (Abeta) plaques and dementia. Autopsy studies suggest that
      Abeta plaques first appear in the cerebral cortex while subcortical plaques are
      present only later in the disease course. The presence of abundant plaques in
      both cortex and striatum is more strongly correlated with the presence of
      dementia than cortical Abeta plaques alone. Additionally, detection of striatal
      plaques may allow, for the first time, pathology-based clinical staging of AD.
      Striatal plaques are reportedly identifiable by amyloid imaging but the accuracy
      and reliability of striatal amyloid imaging has never been tested against
      postmortem histopathology. To determine this, we correlated the presence of
      histopathologically-demonstrated striatal Abeta deposits with a visually positive
      panel consensus decision of a positive [18F]flutemetamol striatal PET signal in
      68 subjects that later came to autopsy. The sensitivity of [18F]flutemetamol PET
      striatal amyloid imaging, for several defined density levels of histological
      striatal Abeta deposits, ranged between 69% and 87% while the specificity ranged
      between 96% and 100%. Sensitivity increased with higher histological density
      thresholds while the reverse was found for specificity. In general, as compared
      with PET alone, PET with CT had slightly higher sensitivities but slightly lower
      specificities. In conclusion, amyloid imaging of the striatum with
      [18F]flutemetamol PET has reasonable accuracy for the detection of histologically
      demonstrated striatal Abeta plaques when present at moderate or frequent
      densities. Amyloid imaging of the cerebral cortex and striatum together may allow
      for a more accurate clinicopathological diagnosis of AD and enable pathology
      based clinical staging of AD.

PMID- 27031470
TI  - Fibrillar Amyloid-beta Accumulation Triggers an Inflammatory Mechanism Leading to
      Hyperphosphorylation of the Carboxyl-Terminal End of Tau Polypeptide in the
      Hippocampal Formation of the 3*Tg-AD Transgenic Mouse.
AB  - Alzheimer's disease (AD) is a degenerative and irreversible disorder whose
      progressiveness is dependent on age. It is histopathologically characterized by
      the massive accumulation of insoluble forms of tau and amyloid-beta (Abeta)
      asneurofibrillary tangles and neuritic plaques, respectively. Many studies have
      documented that these two polypeptides suffer several posttranslational
      modifications employing postmortem tissue sections from brains of patients with
      AD. In order to elucidate the molecular mechanisms underlying the
      posttranslational modifications of key players in this disease, including Abeta
      and tau, several transgenic mouse models have been developed. One of these models
      is the 3*Tg-AD transgenic mouse, carrying three transgenes encoding APPSWE,
      S1M146V, and TauP301L proteins. To further characterize this transgenicmouse, we
      determined the accumulation of fibrillar Abeta as a function of age in relation
      to the hyperphosphorylation patterns of TauP301L at both its N- and C-terminus in
      the hippocampal formation by immunofluorescence and confocal microscopy.
      Moreover, we searched for the expression of activated protein kinases and
      mediators of inflammation by western blot of wholeprotein extracts from
      hippocampal tissue sections since 3 to 28 months as well. Our results indicate
      that the presence of fibrillar Abeta deposits correlates with a significant
      activation of astrocytes and microglia in subiculum and CA1 regions of
      hippocampus. Accordingly, we also observed a significant increase in the
      expression of TNF-alpha associated to neuritic plaques and glial cells.
      Importantly, there is an overexpression of the stress activated protein kinases
      SAPK/JNK and Cdk-5 in pyramidal neurons, which might phosphorylate several
      residues at the C-terminus of TauP301L. Therefore, the accumulation of Abeta
      oligomers results in an inflammatory environment that upregulates kinases
      involved in hyperphosphorylation of TauP301L polypeptide.

PMID- 27031471
TI  - Do Chinese Researchers Conduct Ethical Research and Use Ethics Committee Review
      in Clinical Trials of Anti-Dementia Drugs? An Analysis of Biomedical Publications
      Originating from China.
AB  - BACKGROUND: Medical research using human participants must conform to the basic
      ethical principles found in the Declaration of Helsinki (DoH) of the World
      Medical Association. OBJECTIVE: The purpose of this review was to assess whether
      journals in China have improved in regard to the fulfillment of ethical
      disclosure procedures for clinical trials of anti-dementia drugs. METHODS: Four
      medical databases were searched for articles reporting clinical trials of oral
      anti-dementia drugs published in China in 2003, 2009, and 2014. The frequencies
      of reporting of informed consent from participants (ICP), approval of a regional
      ethical committee (REC), reference to DoH, and study registration were estimated
      respectively. Statistical analyses were conducted with SPSS v21 software.
      RESULTS: Among those randomized controlled trials published in 2003, 2009, and
      2014, disclosure of REC approval was present for 2.67%, 1.15%, and 6.84%;
      statements of ICP were included in 9.33%, 7.76%, and 17.34%; reference to DoH was
      found for 4.00%, 1.44%, and 7.45%; and study registration reporting was included
      in 2.67%, 2.59%, and 9.28%, respectively. Improvements to reporting rates between
      2009 and 2014 were seen, with more than twice as many trials reporting REC
      approval, ICP, reference to DoH, and study registration compared with 2009.
      CONCLUSION: Compared with 2003 and 2009, reporting rates for REC approval, ICP,
      reference to DoH, and study registration for clinical trials of anti-dementia
      drugs were enhanced in 2014 in the major medical journals of China. However,
      biomedical publications without definite statements of ethical considerations
      remain common, and this continues to be seen in Chinese journals. It is
      imperative that measures are taken to reinforce the ethical protection in
      clinical trials in China.

PMID- 27031473
TI  - Vitamin D Supplementation Appears to Increase Plasma Abeta40 in Vitamin D
      Insufficient Older Adults: A Pilot Randomized Controlled Trial.
AB  - Low plasma amyloid-beta (Abeta) is linked to Alzheimer's disease. Since vitamin D
      cleared brain Abeta in vitro, this 8-week trial examined whether vitamin D
      increased plasma Abeta40. Vitamin D insufficient adults (6/18 M/F; 64.3 +/- 10.9
      y) were randomized to placebo or vitamin (50,000 IU/week) treatments. The vitamin
      group experienced greater plasma Abeta40 change than controls, +14.9 +/- 12.0 and
      +12.8 +/- 12.8 pg/mL (p = 0.045; effect size, 0.228). Change in Abeta40 for older
      participants (>=60 y) was +18.3 +/- 33.6 and -3.2 +/- 44.5 pg/mL for vitamin (n =
      4) and placebo (n = 4) groups (effect size, 0.295). Thus, vitamin D may increase
      plasma Abeta, particularly in older adults, suggesting decreased brain Abeta.

PMID- 27031472
TI  - Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive
      Impairment Subtypes and Interaction with APOE E4 Genotype.
AB  - We examined cortical amyloid-beta (Abeta) levels and interactions with
      apolipoprotein (APOE) E4 genotype status across empirically-derived mild
      cognitive impairment (MCI) subgroups and cognitively normal older adults.
      Participants were 583 ADNI participants (444 MCI, 139 normal controls [NC]) with
      baseline florbetapir positron emission tomography (PET) amyloid imaging and
      neuropsychological testing. Of those with ADNI-defined MCI, a previous cluster
      analysis [1] classified 51% (n = 227) of the current sample as amnestic MCI, 8%
      (n = 37) as dysexecutive/mixed MCI, and 41% (n = 180) as cluster-derived normal
      (cognitively normal). Results demonstrated that the dysexecutive/mixed and
      amnestic MCI groups showed significantly greater levels of amyloid relative to
      the cluster-derived normal and NC groups who did not differ from each other.
      Additionally, 78% of the dysexecutive/mixed, 63% of the amnestic MCI, 42% of the
      cluster-derived normal, and 34% of the NC group exceeded the amyloid positivity
      threshold. Finally, a group by APOE genotype interaction demonstrated that APOE
      E4 carriers within the amnestic MCI, cluster-derived normal, and NC groups showed
      significantly greater amyloid accumulation compared to non-carriers of their
      respective group. Such an interaction was not revealed within the
      dysexecutive/mixed MCI group which was characterized by both greater cognitive
      impairment and amyloid accumulation compared to the other participant groups. Our
      results from the ADNI cohort show considerable heterogeneity in Abeta across all
      groups studied, even within a group of robust NC participants. Findings suggest
      that conventional criteria for MCI may be susceptible to false positive
      diagnostic errors, and that onset of Abeta accumulation may occur earlier in APOE
      E4 carriers compared to non-carriers.

PMID- 27031474
TI  - High Risk of Dementia in Ventricular Enlargement with Normal Pressure
      Hydrocephalus Related Symptoms1.
AB  - BACKGROUND: Differential diagnosis of ventricular enlargement with normal
      pressure hydrocephalus (NPH) related symptoms is challenging. Patients with
      enlarged ventricles often manifest cognitive deterioration but their long-term
      outcome is not well known. OBJECTIVES: We aim to evaluate long-term cognitive
      outcome in patients with enlarged ventricles and clinically suspected NPH.
      METHODS: A neurologist and a neurosurgeon clinically evaluated 468 patients with
      enlarged ventricles and suspected NPH using radiological methods,
      intraventricular pressure monitoring, and frontal cortical brain biopsy. The
      neurologist confirmed final diagnoses after a median follow-up interval of 4.8
      years. RESULTS: Altogether, 232 patients (50%) with enlarged ventricles did not
      fulfill the criteria for shunt surgery. The incidence of dementia among patients
      with enlarged ventricles, and at least one NPH-related symptom with adequate
      follow-up data (n = 446) was high, varying from 77 (iNPH, shunt responders) to
      141/1000 person-years (non-shunted patients with enlarged ventricles). At the end
      of the follow-up, 59% of all these patients were demented. The demented
      population comprised 73% of non-shunted patients with enlarged ventricles, 63% of
      shunted iNPH patients that did not respond to treatment, and 46% of iNPH patients
      that were initially responsive to shunting. The most common cause of dementia was
      Alzheimer's disease (n = 94, 36%), followed by vascular dementia (n = 68, 26%).
      CONCLUSIONS: One-half of patients with enlarged ventricles and clinically
      suspected NPH were not shunted after intraventricular pressure monitoring.
      Dementia caused by various neurodegenerative diseases was frequently seen in
      patients with ventricular enlargement. Thus, careful diagnostic evaluation in
      collaboration with neurologists and neurosurgeons is emphasized.

PMID- 27031475
TI  - Aquaporin-4 and Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia. Although the
      pathogenesis of AD remains unclear, AD is thought to result from an imbalance in
      the production and clearance of amyloid-beta protein (Abeta). Aquaporin-4 (AQP4)
      is the major aquaporin in the mammalian brain, is mostly expressed on astrocytic
      endfeet, and functions as a water transporter. However, the distribution and
      expression of AQP4 are altered in both AD clinical populations and animal models.
      Recent studies have revealed that AQP4 is important to the clearance of Abeta in
      brain via lymphatic clearance, transcytotic delivery, and glial degradation, as
      well as to the synaptic function. Thus, AQP4 likely plays an important role in
      the pathogenesis of AD. Further studies would provide new targets for prevention,
      ultimately leading to improved treatment options for AD.

PMID- 27031476
TI  - Homocysteine and Alzheimer's Disease: Evidence for a Causal Link from Mendelian
      Randomization.
AB  - BACKGROUND/OBJECTIVE: The relationship between plasma homocysteine (Hcy) levels
      and Alzheimer's disease (AD) has been studied for many years, but remains
      controversial. While a recent meta-analysis of epidemiological studies, which
      included observational studies, indicated that homocysteine may be a risk factor
      for AD, there remains a need to further demonstrate this link due to the large
      degree of heterogeneity between studies. Epidemiological studies have certain
      limitations, as their results can be affected by confounding factors and reverse
      causation. In this study, we evaluated the relationship between plasma
      homocysteine and AD by using a Mendelian randomization method to avoid problems
      of confounding bias and reverse causality. METHODS: We searched the PubMed and
      EMBASE databases for reports regarding the MTHFR C677T polymorphism (rs1801133)
      from the time of their inception to September 2015. These reports were combined
      with related observational studies, and used to evaluate the effect of MTHFR
      C677T (rs1801133) on the risk for AD. A recent meta-analysis of genome-wide
      association studies had previously suggested a relationship between homocysteine
      and MTHFR C677T (rs 1801133). RESULTS: Our met-analysis included 34 studies with
      9397 subjects, and demonstrated a significant relationship between plasma total
      homocysteine levels and the risk for AD (OR = 3.37; 95% CI = 1.90-5.95; p =
      2.9*10-5). CONCLUSION: Our meta-analysis demonstrated a causal link between
      plasma total homocysteine and the risk for AD, and provides a new insight into
      the etiology and prevention of AD.

PMID- 27031477
TI  - "Missed" Mild Cognitive Impairment: High False-Negative Error Rate Based on
      Conventional Diagnostic Criteria.
AB  - Mild cognitive impairment (MCI) is typically diagnosed using subjective
      complaints, screening measures, clinical judgment, and a single memory score. Our
      prior work has shown that this method is highly susceptible to false-positive
      diagnostic errors. We examined whether the criteria also lead to "false-negative"
      errors by diagnostically reclassifying 520 participants using novel actuarial
      neuropsychological criteria. Results revealed a false-negative error rate of
      7.1%. Participants' neuropsychological performance, cerebrospinal fluid
      biomarkers, and rate of decline provided evidence that an MCI diagnosis is
      warranted. The impact of "missed" cases of MCI has direct relevance to clinical
      practice, research studies, and clinical trials of prodromal Alzheimer's disease.

PMID- 27031478
TI  - Insight into the Dissociation of Behavior from Histology in Synucleinopathies and
      in Related Neurodegenerative Diseases.
AB  - Recent clinical trials using immunization approaches against Alzheimer's disease
      (AD) have failed to demonstrate improved cognitive functions in patients, despite
      potent suppression in the formation of both senile plaques and other amyloid-beta
      deposits in postmortem brains. Similarly, we observed that treatment with
      ibuprofen, a non-steroidal anti-inflammatory drug, was effective in improving the
      histopathology, such as reducing both protein aggregation and glial activation,
      in the brains of transgenic mice expressing dementia with Lewy bodies-linked
      P123H beta-synuclein. In contrast, only a small improvement in cognitive
      functions was observed in these mice. Collectively, it is predicted that
      histology does not correlate with behavior that is resilient and resistant to
      therapeutic stimuli. Notably, such a 'discrepancy between histology and behavior'
      is reminiscent of AD-like pathologies and incidental Lewy bodies, which are
      frequently encountered in postmortem brains of the elderly who had been
      asymptomatic for memory loss and Parkinsonism during their lives. We suggest that
      'the discrepancy between histology and behavior' may be a universal feature that
      is associated with various aspects of neurodegenerative diseases. Furthermore,
      given that the cognitive reserve is specifically observed in human brains, human
      behavior may be evolutionally distinct from that in other animals, thus,
      contributing to the differential efficiency of therapy between human and lower
      animals, an important issue in the therapy of neurodegenerative diseases.
      Overall, it is important to better understand 'the discrepancy between histology
      and behavior' in the mechanism of neurodegeneration for the development of
      effective therapies against neurodegenerative diseases.

PMID- 27031479
TI  - Development of a Proxy-Free Objective Assessment Tool of Instrumental Activities
      of Daily Living in Mild Cognitive Impairment Using Smart Home Technologies.
AB  - BACKGROUND: The assessment of activities of daily living (ADL) is essential for
      dementia diagnostics. Even in mild cognitive impairment (MCI), subtle deficits in
      instrumental ADL (IADL) may occur and signal a higher risk of conversion to
      dementia. Thus, sensitive and reliable ADL assessment tools are important. Smart
      homes equipped with sensor technology and video cameras may provide a proxy-free
      assessment tool for the detection of IADL deficits. OBJECTIVE: The aim of this
      paper is to investigate the potential of a smart home environment for the
      assessment of IADL in MCI. METHOD: The smart home consisted of a two-room flat
      equipped with activity sensors and video cameras. Participants with either MCI or
      healthy controls (HC) had to solve a standardized set of six tasks, e.g., meal
      preparation, telephone use, and finding objects in the flat. RESULTS: MCI
      participants needed more time (1384 versus 938 seconds, p <  0.001) and scored
      less total points (48 versus 57 points, p <  0.001) while solving the tasks than
      HC. Analyzing the subtasks, intergroup differences were observed for making a
      phone call, operating the television, and retrieving objects. MCI participants
      showed more searching and task-irrelevant behavior than HC. Task performance was
      correlated with cognitive status and IADL questionnaires but not with
      participants' age. CONCLUSION: This pilot study showed that smart home
      technologies offer the chance for an objective and ecologically valid assessment
      of IADL. It can be analyzed not only whether a task is successfully completed but
      also how it is completed. Future studies should concentrate on the development of
      automated detection of IADL deficits.

PMID- 27031480
TI  - Living Alone with Dementia: Prevalence, Correlates and the Utilization of Health
      and Nursing Care Services.
AB  - BACKGROUND: Little is known about the proportion and the characteristics of
      community-dwelling people with dementia (PWD) living alone in Germany.
      OBJECTIVES: To analyze the prevalence of PWD living alone (with and without the
      support of an informal caregiver) and socio-demographical and clinical
      characteristics as well as health and nursing care utilization associated with
      living alone. METHODS: DelpHi-MV (Dementia: Life- and person-centered help in
      Mecklenburg-Western Pomerania) is a general practitioner-based, randomized
      controlled intervention trial. The present analyses are based on baseline data of
      511 patients (>=70 years, community-dwelling) who had screened positive for
      dementia (DemTect <9). RESULTS: N = 251 (51%) of the patients lived alone. PWD
      living alone were statistically significantly more often female, older, and more
      often widowed than those not living alone. About 9% of the patients (n = 24) were
      not supported by any informal caregiver. Regarding the clinical variables
      (cognitive and functional impairment, depression, falls, number of drug-related
      problems, malnutrition, quality of life), there were no statistically significant
      group differences. Patients living alone utilized professional services such as
      home care, help with medication, home-delivered meals, or housekeeping assistance
      significantly more often. Multivariate analyses confirmed these findings.
      CONCLUSION: Our results reveal the high proportion of PWD living alone in
      Germany. PWD living alone did not seem to be at an increased health risk. Our
      findings indicate that living alone with dementia is possible. In order to ensure
      the sufficient provision of health and nursing care services for PWD living
      alone, providers should consider the present results for future planning.

PMID- 27031481
TI  - Community-Dwelling People Screened Positive for Dementia in Primary Care: A
      Comprehensive, Multivariate Descriptive Analysis Using Data from the DelpHi
      Study.
AB  - BACKGROUND: Efficient help and care for people with dementia (PWD) is dependent
      on knowledge about PWD in primary care. OBJECTIVE: This analysis comprehensively
      describes community-dwelling PWD in primary care with respect to various dementia
      care specific variables. METHODS: The analyses are based on baseline data of the
      ongoing general practitioner-based, randomized, controlled intervention trial
      DelpHi-MV (Dementia: life- and person-centered help). 6,838 patients were
      screened for dementia in 136 GP practices; 17.1% were screened positive, 54.4% of
      those agreed to participate and data could be assessed in n = 516 subjects. We
      assessed age, sex, living situation, cognitive status, functional status, level
      of impairment, comorbidities, formal diagnosis of dementia, depression,
      neuropsychiatric symptoms, quality of life, utilization of medical support, and
      pharmacological therapy. RESULTS: Concerning clinical-, dementia-, and health
      related variables, the sample under examination was on average mildly cognitively
      and functionally impaired (MMSE, m = 22.2; BADL, m = 3.7). A level of care was
      assigned in 38.0%. Depression was identified in 15.4% and other frequent
      comorbidities were high blood pressure (83.3%), coronary heart diseases (37.1%),
      cerebrovascular diseases (22.3%), among others. In 48.6%, neuropsychiatric
      symptoms were present in a clinically relevant severity. Pharmacological
      treatment with antidementia medication was received by 25.8% and antidepressant
      medication by 14.0%. Utilization of services was generally low. CONCLUSION: The
      comprehensive description of people screened positive for dementia in primary
      care reveals a complex and unique population of patients. They are considerably
      underdiagnosed and in their majority mildly to moderately affected. More in-depth
      analyses are needed to study relations, associations and interactions between
      different variables.

PMID- 27031482
TI  - Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory
      Performance in Community-Dwelling Older Adults.
AB  - Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region
      specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2
      deoxyglucose positron emission tomography (18F-FDG PET). We investigated
      preclinical disease stage by cross-sectionally examining the association between
      global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake
      value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on
      differences between subjective memory complainers and non-memory complainers. The
      18F-FDG PET regions of interest investigated include the hippocampus, amygdala,
      posterior cingulate, superior parietal, entorhinal cortices, frontal cortex,
      temporal cortex, and inferior parietal region. In the cohort as a whole, verbal
      logical memory immediate recall was positively associated with 18F-FDG PET SUVR
      in both the left hippocampus and right amygdala. There were no associations
      observed between global cognition, delayed recall in logical memory, or visual
      reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into
      subjective memory complainers and non-complainers, verbal logical memory
      immediate recall was positively associated with 18F-FDG PET SUVR in the right
      amygdala in those with subjective memory complaints. There were no significant
      associations observed in non-memory complainers between 18F-FDG PET SUVR in
      regions of interest and cognitive performance. We observed subjective memory
      complaint-specific associations between 18F-FDG PET SUVR and immediate verbal
      memory performance in our cohort, however found no associations between delayed
      recall of verbal memory performance or visual memory performance. It is here
      argued that the neural mechanisms underlying verbal and visual memory performance
      may in fact differ in their pathways, and the characteristic reduction of 18F-FDG
      PET SUVR observed in this and previous studies likely reflects the
      pathophysiological changes in specific brain regions that occur in preclinical
      AD.

PMID- 27031483
TI  - Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in
      Memory Clinic Patients in a Prospective Cohort.
AB  - BACKGROUND: Limited information is available on short-term prognosis of
      Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF) in addition to
      routine diagnostic workup. OBJECTIVE: This study aims to investigate the added
      prognostic value of AD CSF biomarkers. METHODS: In a prospective cohort study,
      clinical experts predicted cognitive and functional symptoms in 114 memory clinic
      patients by assessing comprehensive routine diagnostic test information (patient
      history, and physical, neurological, psychiatric, neuropsychological, and MRI
      examinations), without and with CSF biomarkers. The reference standard was the
      'observed clinically relevant decline' using baseline and 1- and 2-year follow-up
      information. RESULTS: Decline over a 2-year period was observed in 51% of all
      participants (3% in SMC, 48% in MCI, 90% in mild dementia). In the total sample,
      the accuracy of predicted decline did not differ significantly between routine
      assessment without (79% correctly predicted) and with (74% correctly predicted)
      CSF biomarkers. Subgroup analyses revealed 25 (83%) correct predictions in SMC,
      30 (68%) in MCI, and 35 (88%) in dementia without the use of CSF; and 21 (70%),
      27 (61%), and 36 (90%), respectively, with the use of CSF in addition to the
      routine assessment. CONCLUSION: AD CSF biomarkers did not increase accuracy of 2
      year prognosis of cognitive and functional decline when added to routine
      diagnostic workup. This suggests that the standard diagnostic workup without CSF
      biomarkers allows fairly accurate predictions for the short-term course of
      symptoms. Routine AD biomarkers in CSF have limited prognostic value over 2 years
      in persons with a suspected cognitive disorder.

PMID- 27031484
TI  - A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic
      Resonance Imaging.
AB  - Amyloid binding molecules with greater hydrophilicity than existing ligands were
      synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid
      deposits in dog brain and human brain tissue ex vivo. The ligand was used to
      prepare novel amyloid-targeted liposomal nanoparticles. The preparation was
      tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates
      and Indocyanine green were included in the particles for visualization by MRI and
      near-infrared microscopy. Upon intravenous injection, the particles successfully
      traversed the blood-brain barrier in these mice, and bound to the plaques.
      Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated
      elevated signal in the brains of mice with amyloid plaques present. No signal was
      observed in amyloid-negative mice, or in amyloid-positive mice injected with an
      untargeted version of the same agent. The MRI results were confirmed by
      immunohistochemical and fluorescent microscopic examination of mouse brain
      sections, showing colocalization of the fluorescent tags and amyloid deposits.

PMID- 27031485
TI  - Cognitive Reserve in Alzheimer's Dementia: Diagnostic Accuracy of a Testing-the
      Limits Paradigm.
AB  - Individuals with higher cognitive reserve are more able to cope with pathological
      brain alterations, potentially due to the application of more efficient cognitive
      strategies. The extent to which an individual's cognitive performance can be
      increased by advantageous conditions differs substantially between patients with
      Alzheimer's dementia (AD) and healthy older adults and can be assessed with the
      Testing-the-Limits (TtL) approach. Thus, TtL has been proposed as a tool for the
      early diagnosis of AD. Here, we report the diagnostic accuracy of a memory TtL
      paradigm to discriminate between AD patients and controls. The TtL paradigm was
      administered to 57 patients with clinically diagnosed AD and 94 controls. It
      consisted of a pre-test condition, representing baseline cognitive performance,
      the presentation of an encoding strategy, and two subsequent post-test
      conditions, representing learning potential. Receiver operating characteristic
      (ROC) curves were analyzed for each condition in order to receive optimal cutoff
      points along with their sensitivity and specificity and to compare the diagnostic
      accuracy of the conditions. Differentiation between AD patients and controls,
      indicated by the area under the ROC curve, increased significantly for the TtL
      post-test and total error scores compared to the pre-test score. The combined
      error score in the two post-tests could differentiate between AD patients and
      controls with a sensitivity of 0.93 and a specificity of 0.80. The presented
      approach can be carried out in 25 minutes and thus constitutes a time- and cost
      effective way to diagnose AD with high accuracy.

PMID- 27031487
TI  - Low Serum Insulin-Like Growth Factor-I Predicts Cognitive Decline in Alzheimer's
      Disease.
AB  - BACKGROUND: The relationship between the insulin-like growth factor-I (IGF-I)
      system and Alzheimer's disease (AD) is mostly based on transversal studies. It
      remains, however, to demonstrate whether IGF-I is associated with cognitive
      decline over time in AD. OBJECTIVE: The objective of the study was to analyze the
      course of cognitive decline of AD subjects over a 24-month period in relation to
      serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) measured
      at baseline. METHODS: Data are from the SIGAL follow-up study. IGF-I and IGFBP-3
      were measured in AD subjects who performed a Mini-Mental State Examination (MMSE)
      every 6 months for 2 years. MMSE course was analyzed using a mixed model with
      random intercept and slope function. RESULTS: Among the 200 AD participants, 146
      (mean age = 81.1 (standard deviation (SD) = 5.9) years, 62.6% of women) had at
      least one follow-up visit. Mean IGF-I at baseline was 147.8 (74.2) ng/mL. Hundred
      forty-six participants (62.6%) had at least one follow-up visit. Mean MMSE was
      21.7 (4.7)/30 and dropped on average by 2.28 points per year. MMSE decline was
      steeper among participants with lower IGF-I. For each decrease of 1 SD of IGF-I,
      subjects lost an additional 0.63 points per year in MMSE, e.g., participants with
      IGF-I level of 74 ng/mL lost 2.91 MMSE points per year whereas participants with
      IGF-I of 222 ng/mL lost 1.65 MMSE points per year. There was no association
      between IGFBP-3 and cognitive decline. CONCLUSION: Lower baseline serum IGF-I was
      associated with faster cognitive decline in AD over a 2-year period.

PMID- 27031486
TI  - Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non
      Demented Elderly.
AB  - Increasingly, clinical trials for Alzheimer's disease (AD) are being conducted
      earlier in the disease phase and with biomarker confirmation using in vivo
      amyloid PET imaging or CSF tau and Abeta measures to quantify pathology. However,
      making such a pre-clinical AD diagnosis is relatively costly and the screening
      failure rate is likely to be high. Having a blood-based marker that would reduce
      such costs and accelerate clinical trials through identifying potential
      participants with likely pre-clinical AD would be a substantial advance. In order
      to seek such a candidate biomarker, discovery phase proteomic analyses using 2DGE
      and gel-free LC-MS/MS for high and low molecular weight analytes were conducted
      on longitudinal plasma samples collected over a 12-year period from non-demented
      older individuals who exhibited a range of 11C-PiB PET measures of amyloid load.
      We then sought to extend our discovery findings by investigating whether our
      candidate biomarkers were also associated with brain amyloid burden in disease,
      in an independent cohort. Seven plasma proteins, including A2M, Apo-A1, and
      multiple complement proteins, were identified as pre-clinical biomarkers of
      amyloid burden and were consistent across three time points (p <  0.05). Five of
      these proteins also correlated with brain amyloid measures at different stages of
      the disease (q <  0.1). Here we show that it is possible to detect a plasma based
      biomarker signature indicative of AD pathology at a stage long before the onset
      of clinical disease manifestation. As in previous studies, acute phase reactants
      and inflammatory markers dominate this signature.

PMID- 27031488
TI  - Reelin in Alzheimer's Disease, Increased Levels but Impaired Signaling: When More
      is Less.
AB  - In the continuing search for proteins that play a role in Alzheimer's disease
      (AD) and that are related to the pathological hallmarks, those that influence
      cognitive function and that constitute potential therapeutic targets deserve
      special interest. Reelin is a signaling protein that is involved in a cascade of
      cytoplasmic events that control tau phosphorylation and that regulate synaptic
      neurotransmission, plasticity, and memory. Both Reelin expression and
      glycosylation are modulated by amyloid-beta (Abeta), suggesting that the activity
      of Reelin could be affected in AD and hence, its possible influence on this
      pathology should be taken into consideration. The levels of Reelin in the brain
      of AD patients appear to be altered and interestingly, disrupted Reelin signaling
      is associated with increased tau phosphorylation as well as with amyloid-beta
      protein precursor processing. We discuss here the somewhat contradictory data
      regarding Reelin levels in AD and we evaluate the processing of the Reelin
      receptor, ApoER2, and other downstream events, such as the phosphorylation of the
      intracellular adapter Dab1. Together with brain Reelin levels, these changes may
      represent a relevant read-out of Reelin signaling in the human brain.

PMID- 27031489
TI  - Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of
      Practice.
AB  - Zeng et al.'s Ethics Review highlights some of the challenges associated with
      clinical research in China. They found that only a minority of published clinical
      trials of anti-dementia drugs reported that they fulfilled the basic ethical
      principles as outlined in the Declaration of Helsinki. With recent reports of
      scientific misconduct from China, there is an urgent need to find approaches to
      compel researchers to adhere to ethical research practices. This problem does not
      call for a simple solution, but if forces are joined with governmental
      regulations, education in ethics issues for medical researchers, and strong
      reinforcement by Chinese journal editors not to publish studies with these flaws,
      then research ethics and publication standards will probably improve. Other
      solutions to foster ethical practice of drug trials are discussed including
      Chinese initiatives directed at managing conflict of interest from the
      pharmaceutical industry and educating clinical researchers.

PMID- 27031490
TI  - Association between Antipsychotic Drugs and Mortality in Older Persons with
      Alzheimer's Disease: A Systematic Review and Meta-Analysis.
AB  - Antipsychotic drugs have been inconsistently associated with death risk of
      Alzheimer's disease (AD) patients. Herein we review and quantitatively summarize
      the evidence from epidemiological studies. Pertinent studies were identified by
      searching PubMed and Cochrane Library Register of Controlled Trials through 20
      December 2015. The DerSimonian and Laird random effect model was adopted as the
      pooling method. Twelve studies from nine articles with 11,463 participants were
      included. The pooled RR of observational studies was 1.36 (95% CI, 0.83-2.24; I2
      = 94.9%) for antipsychotic drugs users versus individuals who were not exposed to
      antipsychotic drugs. When the three studies that were key contributors to the
      high heterogeneity were excluded, the pooled RR was 2.08 (95% CI 1.39 to 3.13).
      The result of one double-blind randomized clinical trial indicated that
      antipsychotic drugs nearly doubled the risk of death in AD patients. In
      conclusion, there is no evidence of absence of association between antipsychotic
      drugs' use with death risk of AD patients. Careful assessments of potential
      benefits and risks should be made before prescribing antipsychotics for treatment
      of psychosis symptoms and behavioral problems of AD patients.

PMID- 27031491
TI  - Short-Term Effects of Rhythmic Sensory Stimulation in Alzheimer's Disease: An
      Exploratory Pilot Study.
AB  - This study assessed the effect of stimulating the somatosensory system of
      Alzheimer's disease (AD) patients at three stages of their illness with 40 Hz
      sound. In this AB cross-over study design, 18 participants (6 mild, 6 moderate, 6
      severe) each participated in 13 sessions: one intake and 12 treatment. Treatment
      A consisted of 40 Hz sound stimulation and Treatment B consisted of visual
      stimulation using DVDs, each provided twice a week over 6 weeks for a total of 6
      times per treatment. Outcome measures included: St. Louis University Mental
      Status Test (SLUMS), Observed Emotion Rating Scale, and behavioral observation by
      the researcher. Data were submitted to regression analysis for the series of 6
      SLUMS scores in treatment A and 6 scores in B with comparison by group. The
      slopes for the full sample and subgroups in the 40 Hz treatment were all
      significant beyond alpha = 0.05, while those for the DVD were not. A thematic
      analysis of qualitative observations supported the statistical findings. 40 Hz
      treatment appeared to have the strongest impact on persons with mild and moderate
      AD. Results are promising in terms of a potential new treatment for persons with
      AD, and further research is needed.

PMID- 27031492
TI  - Amyloid-Related Imaging Abnormalities (ARIA) in Immunotherapy Trials for
      Alzheimer's Disease: Need for Prognostic Biomarkers?
AB  - At the 8th International Conference on Clinical Trials in Alzheimer's Disease
      held November 5-7, 2015 in Barcelona, Spain, promising data were presented on two
      candidate Alzheimer's disease immunotherapeutic agents, gantenerumab and
      aducanumab. Trial results demonstrated that the implementation of cerebrospinal
      fluid and Abeta-PET biomarkers improves trial enrichment and outcome, which has
      led to a change in targeting strategy as clinical trials would be conducted with
      earlier, even presymptomatic, stages of the disease. Promising findings of
      outcomes, as measured by Abeta-PET and cerebrospinal fluid tau and P-tau, were,
      nevertheless, associated with antibody dose-dependent increased risk of severe
      adverse effects, specifically amyloid-related imaging abnormalities (ARIA).
      Aducanumab was associated with concomitant time-, dose-, and APOE-related
      incidence of ARIA in more than one-half of the patients within the high-dose arm.
      The future challenge will thus be to find biomarkers more favorably balanced
      between effective dosing of antibody to remove Abeta versus dosing to limit
      deleterious side effects. Interest was shown by Roche and Biogen, which promoted
      high-dose phase 3 trials. However, this generated some concerns related to a
      reasonable expected further increase in the incidence of severe side effects.
      What has been learned is challenging primary industry strategies for following-up
      and monitoring safety and effectiveness of anti-Abeta antibodies in clinical
      trials. Here, we debate the issue of what is an acceptable balance of treatment
      side effects, i.e., therapeutic-induced ARIA, versus the positive prospects.
      Indeed, implementation of biomarkers for ARIA might increase value and reduce
      waste in the design of immunotherapy trials of Alzheimer's disease.

PMID- 27031494
TI  - Metalloprobes: Fluorescence imaging of multidrug resistance (MDR1) P-Glycoprotein
      (Pgp)-mediated functional transport activity in cellulo.
AB  - Radiolabeled metalloprobes offer sensitive tools for evaluating quantitative
      accumulation of chemical entities within pooled cell populations. Although
      beneficial in translational nuclear imaging, this method precludes interrogation
      of effects resulting from variations at a single cell level, within the same
      segment of cell population. Compared with radiotracer bioassays, fluorescence
      imaging offers a cost-efficient technique to assess accumulation of metalloprobes
      at a single cell level, and determine their intracellular localization under live
      cell conditions. To evaluate, whether or not radiotracer assay and fluorescence
      imaging provide complementary information on utility of metalloprobes to assess
      functional expression of P-glycoprotein (Pgp) on plasma membrane of tumor cells,
      imaging studies of fluorescent cationic Ga(III)-ENBDMPI (bis(3-ethoxy-2-hydroxy
      benzylidene)-N,N'-bis(2,2-dimethyl-3-amino-propyl)ethylenediamine) and its
      neutral counterpart Zn(II)-ENBDMPI are performed. While the uptake profiles of
      the cationic metalloprobe are inversely proportional to expression of Pgp in
      tumor cells, the accumulation profiles of the neutral Zn(II)-ENBDMPI in non-MDR
      and MDR cells are not significantly impacted. The cationic Ga(III)-ENBDMPI maps
      with Mito-Tracker Red, thereby confirming localization within mitochondria of non
      MDR (Pgp-) cells. Depolarization of both plasmalemmal and mitochondrial
      potentials decreased retention of the cationic Ga(III)-ENBDMPI within the
      mitochondria. Additionally, LY335979, an antagonist-induced accumulation of the
      cationic Ga(III) metalloprobe in MDR (Pgp+) cells indicated specificity of the
      agent. Compared with traits of Ga(III)-ENBDMPI as a Pgp recognized substrate,
      Zn(II)-ENBDMPI demonstrated uptake in both MDR and non-MDR cells thus indicating
      the significance of overall molecular charge in mediating Pgp recognition
      profiles. Combined data indicate that live cell imaging can offer a cost
      effective methodology for monitoring functional Pgp expression.

PMID- 27031495
TI  - Attentional effects on rule extraction and consolidation from speech.
AB  - Incidental learning plays a crucial role in the initial phases of language
      acquisition. However the knowledge derived from implicit learning, which is based
      on prediction-based mechanisms, may become explicit. The role that attention
      plays in the formation of implicit and explicit knowledge of the learned material
      is unclear. In the present study, we investigated the role that attention plays
      in the acquisition of non-adjacent rule learning from speech. In addition, we
      also tested whether the amount of attention during learning changes the
      representation of the learned material after a 24h delay containing sleep. For
      that, we developed an experiment run on two consecutive days consisting on the
      exposure to an artificial language that contained non-adjacent dependencies
      (rules) between words whereas different conditions were established to manipulate
      the amount of attention given to the rules (target and non-target conditions).
      Furthermore, we used both indirect and direct measures of learning that are more
      sensitive to implicit and explicit knowledge, respectively. Whereas the indirect
      measures indicated that learning of the rules occurred regardless of attention,
      more explicit judgments after learning showed differences in the type of learning
      reached under the two attention conditions. 24 hours later, indirect measures
      showed no further improvements during additional language exposure and explicit
      judgments indicated that only the information more robustly learned in the
      previous day, was consolidated.

PMID- 27031496
TI  - Library design and screening protocol for artificial metalloenzymes based on the
      biotin-streptavidin technology.
AB  - Artificial metalloenzymes (ArMs) based on the incorporation of a biotinylated
      metal cofactor within streptavidin (Sav) combine attractive features of both
      homogeneous and enzymatic catalysts. To speed up their optimization, we present a
      streamlined protocol for the design, expression, partial purification and
      screening of Sav libraries. Twenty-eight positions have been subjected to
      mutagenesis to yield 335 Sav isoforms, which can be expressed in 24-deep-well
      plates using autoinduction medium. The resulting cell-free extracts (CFEs)
      typically contain >1 mg of soluble Sav. Two straightforward alternatives are
      presented, which allow the screening of ArMs using CFEs containing Sav. To
      produce an artificial transfer hydrogenase, Sav is coupled to a biotinylated
      three-legged iridium pianostool complex Cp*Ir(Biot-p-L)Cl (the cofactor). To
      screen Sav variants for this application, you would determine the number of free
      binding sites, treat them with diamide, incubate them with the cofactor and then
      perform the reaction with your test compound (the example used in this protocol
      is 1-phenyl-3,4-dihydroisoquinoline). This process takes 20 d. If you want to
      perform metathesis reactions, Sav is coupled to a biotinylated second-generation
      Grubbs-Hoveyda catalyst. In this application, it is best to first immobilize Sav
      on Sepharose-iminobiotin beads and then perform washing steps. Elution from the
      beads is achieved in an acidic reaction buffer before incubation with the
      cofactor. Catalysis using your test compound (in this protocol, 2-(4-(N,N
      diallylsulfamoyl)phenyl)-N,N,N-trimethylethan-1-aminium iodide) is performed
      using the formed metalloenzyme. Screening using this approach takes 19 d. 

PMID- 27031498
TI  - Iridium-Catalyzed Formal [4 + 1] Cycloaddition of Biphenylenes with Alkenes
      Initiated by C-C Bond Cleavage for the Synthesis of 9,9-Disubstituted Fluorenes.
AB  - An Ir-catalyzed intermolecular reaction of biphenylenes as a C4 unit with various
      alkenes as a C1 unit gave 9,9-disubstituted fluorenes in moderate to high yields.
      Preliminary mechanistic studies revealed that this formal [4 + 1] cycloaddition
      probably proceeds via C-C bond cleavage, alkene insertion, beta-hydrogen
      elimination, intramolecular alkene insertion, and then reductive elimination. An
      example of enantioselective reaction was also disclosed. 

PMID- 27031497
TI  - Detecting DNA double-stranded breaks in mammalian genomes by linear amplification
      mediated high-throughput genome-wide translocation sequencing.
AB  - Unbiased, high-throughput assays for detecting and quantifying DNA double
      stranded breaks (DSBs) across the genome in mammalian cells will facilitate basic
      studies of the mechanisms that generate and repair endogenous DSBs. They will
      also enable more applied studies, such as those to evaluate the on- and off
      target activities of engineered nucleases. Here we describe a linear
      amplification-mediated high-throughput genome-wide sequencing (LAM-HTGTS) method
      for the detection of genome-wide 'prey' DSBs via their translocation in cultured
      mammalian cells to a fixed 'bait' DSB. Bait-prey junctions are cloned directly
      from isolated genomic DNA using LAM-PCR and unidirectionally ligated to bridge
      adapters; subsequent PCR steps amplify the single-stranded DNA junction library
      in preparation for Illumina Miseq paired-end sequencing. A custom bioinformatics
      pipeline identifies prey sequences that contribute to junctions and maps them
      across the genome. LAM-HTGTS differs from related approaches because it detects a
      wide range of broken end structures with nucleotide-level resolution. Familiarity
      with nucleic acid methods and next-generation sequencing analysis is necessary
      for library generation and data interpretation. LAM-HTGTS assays are sensitive,
      reproducible, relatively inexpensive, scalable and straightforward to implement
      with a turnaround time of <1 week. 

PMID- 27031499
TI  - Comparison of W-Plasty vs Traditional Straight-Line Techniques for Primary
      Paramedian Forehead Flap Donor Site Closure.
AB  - IMPORTANCE: The paramedian forehead flap (PMFF) donor site scar is hard to
      disguise and may be a source of patient dissatisfaction. OBJECTIVE: To evaluate
      the aesthetic outcome of W-plasty vs traditional straight-line (SL) closure
      techniques of the PMFF donor site. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective cohort study was conducted at the University of California, San
      Francisco Medical Center. Clinical history and operative reports were reviewed
      for 31 patients who underwent a PMFF procedure performed between November 1,
      2011, and May 29, 2014. Blinded photographic analysis of postoperative
      photographs was performed. INTERVENTIONS: The pedicled component of the PMFF was
      raised primarily with either a W-plasty or traditional SL design. MAIN OUTCOMES
      AND MEASURES: Standard photographs of the donor site, obtained at least 90 days
      after surgery, were reviewed and scored in a blinded fashion by 4 dermatologic
      surgeons using a 100-point visual analog scale (from 0 [worst possible outcome]
      to 100 [best possible outcome]) and a 5-point Likert scale (from very poor to
      excellent). Interrater reliability was assessed via Cronbach alpha testing.
      RESULTS: All 31 forehead flaps survived during this study period; 16 PMFFs were
      raised with the W-plasty technique and 15 were raised with the SL technique. The
      W-plasty and SL groups were similar in terms of age, sex, and race/ethnicity
      (mean [SD] age, 68.4 [12.4] vs 61.8 [11.6] years; 13 [84%] vs 9 [60%] men; and 15
      [94%] vs 13 [87%] white). Patients undergoing W-plasty closure had significantly
      higher mean visual analog scale scores compared with those undergoing SL closure
      (72.8 [18.3] vs 65.6 [18.1]; P = .03). Mean Likert scale scores for W-plasty were
      higher than those for SL closure, but the difference was not significant (3.77
      [1.02] vs 3.43 [0.98]; P = .08). Overall interrater reliability for the visual
      analog scale and Likert scale scores were 0.67 and 0.58, respectively.
      CONCLUSIONS AND RELEVANCE: Patients undergoing PMFF donor site closure using a
      primary W-plasty technique demonstrated better mean scar appearance of the
      forehead donor site compared with SL closure. The primary W-plasty technique did
      not result in any PMFF losses and should be considered for appropriate patients.
      LEVEL OF EVIDENCE: 3.

PMID- 27031500
TI  - Chemical Composition and Food Potential of Pachymerus nucleorum Larvae
      Parasitizing Acrocomia aculeata Kernels.
AB  - Insect consumption as food is culturally practiced in various regions of the
      world. In Brazil, there are more than 130 species of edible insects registered,
      from nine orders, among which stands out the Coleoptera. The larva of the beetle
      Pachymerus nucleorum Fabricius, 1792, grows into the bocaiuva fruit (Acrocomia
      aculeata (Jacq.) Lodd. Ex Mart., 1845), which has proven nutritional quality. The
      aim of this work was to evaluate the nutritional potential of P. nucleorum larvae
      compared to bocaiuva kernels for human consumption. Proteins were the second
      largest portion of the larvae nutritional composition (33.13%), with percentage
      higher than the bocaiuva kernels (14.21%). The larval lipid content (37.87%) was
      also high, very close to the kernels (44.96%). The fraction corresponding to
      fatty acids in the oil extracted from the larvae was 40.17% for the saturated and
      46.52% for the unsaturated. The antioxidant activity value was 24.3 uM trolox/g
      of oil extracted from larvae. The larvae tryptic activity was 0.032+/-0.006 nmol
      BAPNA/min. Both the larvae and the bocaiuva kernel presented absence of anti
      nutritional factors. These results favor the use of P. nucleorum larvae as food,
      which are a great protein and lipid sources with considerable concentrations of
      unsaturated fatty acids compared to the bocaiuva kernel. 

PMID- 27031501
TI  - A combined computational and experimental investigation of the oxidative ring
      opening of cyclic ethers by oxoammonium cations.
AB  - The propensity of oxoammonium cations to facilitate the oxidative ring-opening of
      cyclic ethers to their corresponding distal hydroxy ketones is investigated. The
      reaction has been evaluated using experimental and computational methods to gain
      deeper insight into trends in reactivity. 

PMID- 27031502
TI  - Identification of a Tumor Specific, Active-Site Mutation in Casein Kinase 1alpha
      by Chemical Proteomics.
AB  - We describe the identification of a novel, tumor-specific missense mutation in
      the active site of casein kinase 1alpha (CSNK1A1) using activity-based
      proteomics. Matched normal and tumor colon samples were analyzed using an ATP
      acyl phosphate probe in a kinase-targeted LC-MS2 platform. An anomaly in the
      active-site peptide from CSNK1A1 was observed in a tumor sample that was
      consistent with an altered catalytic aspartic acid. Expression and analysis of
      the suspected mutant verified the presence of asparagine in the probe-labeled,
      active-site peptide for CSNK1A1. Genomic sequencing of the colon tumor samples
      confirmed the presence of a missense mutation in the catalytic aspartic acid of
      CSNK1A1 (GAC->AAC). To our knowledge, the D163N mutation in CSNK1A1 is a newly
      defined mutation to the conserved, catalytic aspartic acid of a protein kinase
      and the first missense mutation identified using activity-based proteomics. The
      tumorigenic potential of this mutation remains to be determined. 

PMID- 27031503
TI  - Prevalence and Geographical Variation of Prothrombin G20210A Mutation in Patients
      with Cerebral Vein Thrombosis: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To compare the prevalence of prothrombin G20210A in patients with
      objectively confirmed cerebral vein or cortical vein thrombosis against healthy
      controls, and evaluate geographical variations. DESIGN: Systematic review and
      meta-analysis of case control studies. METHODS: We conducted a systematic review
      of electronic databases including MEDLINE and EMBASE. The main outcome was the
      prevalence of prothrombin G20210A in patients with objectively confirmed cerebral
      vein or cortical vein thrombosis; we also analyzed individual country variations
      in the prevalence. The random-effects model OR was used as the primary outcome
      measure. RESULTS: In total 19 studies evaluated 868 cases of cerebral venous
      thrombosis and 3981 controls. Prothrombin G20210A was found in 103/868 of the
      patients with cerebral venous thrombosis and 105/3999 of the healthy controls
      [random effects pooled OR 5.838, 95% CI 3.96 to 8.58; I217.9%]. The prevalence of
      prothrombin G20210A was significantly elevated in Italian studies (OR 9.69), in
      Brazilian studies (OR 7.02), and in German studies (OR 3.77), but not in Iranian
      studies (OR 0.98). CONCLUSION: Prothrombin G20210A is significantly associated
      with cerebral venous thrombosis when compared to healthy controls, although this
      association is highly dependent on the country of origin.

PMID- 27031504
TI  - Quantification of Ellipsoid Zone Changes in Retinitis Pigmentosa Using en Face
      Spectral Domain-Optical Coherence Tomography.
AB  - IMPORTANCE: New methods are needed to quantify the change in the outer retinal
      structures in retinitis pigmentosa (RP). OBJECTIVE: To implement an alternate
      method for tracking ellipsoid zone (EZ) changes in RP by quantifying the EZ area
      on en face spectral domain-optical coherence tomographic (SD-OCT) images. DESIGN,
      SETTING, AND PARTICIPANTS: Data for this observational case study were collected
      at the Department of Ophthalmology, University of California, Los Angeles, from
      May 1 to July 30, 2015, and included SD-OCT images of a subset of patients from
      the Trial of Oral Valproic Acid for Retinitis Pigmentosa. To be eligible for the
      en face OCT subanalysis, the preserved EZ area was required to be limited to the
      SD-OCT scanning field. Cases in which the EZ band extended to the margins of any
      B-scan or the most superior or inferior B-scan were excluded. The SD-OCT images
      of all included cases were imported into the manufacturer's software to generate
      en face images at the level of the EZ. Two certified SD-OCT graders independently
      delineated the boundaries of the preserved EZ on the en face images. MAIN
      OUTCOMES AND MEASURES: Comparison of the 2 masked gradings of the generated en
      face images of patients with RP for agreement between the graders and the
      validity of the method. RESULTS: Of the 43 available patients with volume SD-OCT
      data, 45 eyes of 24 patients met the eligibility criteria and were included in
      this subanalysis. Every patient had 2 visits that were 1 year apart, which
      included a total of 90 en face OCT images that were graded. The mean (SD)
      absolute difference and percentage difference between the 2 independent graders
      for each visit were 0.08 (0.10) mm2 and 4.5% (5.9%), respectively. The EZ area
      determined by the 2 graders showed excellent agreement with an intraclass
      correlation coefficient of 0.996 (95% CI, 0.995-0.997; P < .001). CONCLUSIONS AND
      RELEVANCE: Quantification of the preserved EZ area on en face SD-OCT images of
      patients with RP is a valid and reproducible method. En face SD-OCT
      quantification may be a useful tool for monitoring the EZ changes of patients
      with advanced RP and a useful outcome measurement variable in therapeutic trials.

PMID- 27031505
TI  - Ultra-Deep Sequencing of HIV-1 near Full-Length and Partial Proviral Genomes
      Reveals High Genetic Diversity among Brazilian Blood Donors.
AB  - BACKGROUND: Here, we aimed to gain a comprehensive picture of the HIV-1 diversity
      in the northeast and southeast part of Brazil. To this end, a high-throughput
      sequencing-by-synthesis protocol and instrument were used to characterize the
      near full length (NFLG) and partial HIV-1 proviral genome in 259 HIV-1 infected
      blood donors at four major blood centers in Brazil: Pro-Sangue foundation (Sao
      Paulo state (SP), n 51), Hemominas foundation (Minas Gerais state (MG), n 41),
      Hemope foundation (Recife state (PE), n 96) and Hemorio blood bank (Rio de
      Janeiro (RJ), n 70). MATERIALS AND METHODS: A total of 259 blood samples were
      obtained from 195 donors with long-standing infections and 64 donors with a lack
      of stage information. DNA was extracted from the peripheral blood mononuclear
      cells (PBMCs) to amplify the HIV-1 NFLGs from five overlapping fragments. The
      amplicons were molecularly bar-coded, pooled, and sequenced by Illumina paired
      end protocol. RESULTS: Of the 259 samples studied, 208 (80%) NFLGs and 49 (18.8%)
      partial fragments were de novo assembled into contiguous sequences and
      successfully subtyped. Of these 257 samples, 183 (71.2%) were pure subtypes
      consisting of clade B (n = 167, 65%), C (n = 10, 3.9%), F1 (n = 4, 1.5%), and D
      (n = 2, 0.7%). Recombinant viruses were detected in 74 (28.8%) samples and
      consist of unique BF1 (n = 41, 15.9%), BC (n = 7, 2.7%), BCF1 (n = 4, 1.5%), CF1
      and CDK (n = 1, 0.4%, each), CRF70_BF1 (n = 4, 1.5%), CRF71_BF1 (n = 12, 4.7%),
      and CRF72_BF1 (n = 4, 1.5%). Evidence of dual infection was detected in four
      patients coinfected with the same subtype (n = 3) and distinct subtype (n = 1).
      CONCLUSION: Based on this work, subtype B appears to be the prevalent subtype
      followed by a high proportion of intersubtype recombinants that appeared to be
      arising continually in this country. Our study represents the largest analysis of
      the viral NFLG ever undertaken worldwide and provides insights into the
      understanding the genesis of the HIV-1 epidemic in this particular area of South
      America and informs vaccine design and clinical trials.

PMID- 27031506
TI  - Assessing Communication Skills of Medical Students in Objective Structured
      Clinical Examinations (OSCE)--A Systematic Review of Rating Scales.
AB  - BACKGROUND: Teaching and assessment of communication skills have become essential
      in medical education. The Objective Structured Clinical Examination (OSCE) has
      been found as an appropriate means to assess communication skills within medical
      education. Studies have demonstrated the importance of a valid assessment of
      medical students' communication skills. Yet, the validity of the performance
      scores depends fundamentally on the quality of the rating scales used in an OSCE.
      Thus, this systematic review aimed at providing an overview of existing rating
      scales, describing their underlying definition of communication skills,
      determining the methodological quality of psychometric studies and the quality of
      psychometric properties of the identified rating scales. METHODS: We conducted a
      systematic review to identify psychometrically tested rating scales, which have
      been applied in OSCE settings to assess communication skills of medical students.
      Our search strategy comprised three databases (EMBASE, PsycINFO, and PubMed),
      reference tracking and consultation of experts. We included studies that reported
      psychometric properties of communication skills assessment rating scales used in
      OSCEs by examiners only. The methodological quality of included studies was
      assessed using the COnsensus based Standards for the selection of health status
      Measurement INstruments (COSMIN) checklist. The quality of psychometric
      properties was evaluated using the quality criteria of Terwee and colleagues.
      RESULTS: Data of twelve studies reporting on eight rating scales on communication
      skills assessment in OSCEs were included. Five of eight rating scales were
      explicitly developed based on a specific definition of communication skills. The
      methodological quality of studies was mainly poor. The psychometric quality of
      the eight rating scales was mainly intermediate. DISCUSSION: Our results reveal
      that future psychometric evaluation studies focusing on improving the
      methodological quality are needed in order to yield psychometrically sound
      results of the OSCEs assessing communication skills. This is especially important
      given that most OSCE rating scales are used for summative assessment, and thus
      have an impact on medical students' academic success.

PMID- 27031507
TI  - Lack of Correlation between Stem-Cell Proliferation and Radiation- or Smoking
      Associated Cancer Risk.
AB  - BACKGROUND: A recent paper by Tomasetti and Vogelstein (Science 2015 347 78-81)
      suggested that the variation in natural cancer risk was largely explained by the
      total number of stem-cell divisions, and that most cancers arose by chance. They
      proposed an extra-risk score as way of distinguishing the effects of the
      stochastic, replicative component of cancer risk from other causative factors,
      specifically those due to the external environment and inherited mutations.
      OBJECTIVES: We tested the hypothesis raised by Tomasetti and Vogelstein by
      assessing the degree of correlation of stem cell divisions and their extra-risk
      score with radiation- and tobacco-associated cancer risk. METHODS: We fitted a
      variety of linear and log-linear models to data on stem cell divisions per year
      and cumulative stem cell divisions over lifetime and natural cancer risk, some
      taken from the paper of Tomasetti and Vogelstein, augmented using current US
      lifetime cancer risk data, and also radiation- and tobacco-associated cancer
      risk. RESULTS: The data assembled by Tomasetti and Vogelstein, as augmented here,
      are inconsistent with the power-of-age relationship commonly observed for cancer
      incidence and the predictions of a multistage carcinogenesis model, if one makes
      the strong assumption of homogeneity of numbers of driver mutations across cancer
      sites. Analysis of the extra-risk score and various other measures (number of
      stem cell divisions per year, cumulative number of stem cell divisions over life)
      considered by Tomasetti and Vogelstein suggests that these are poorly predictive
      of currently available estimates of radiation- or smoking-associated cancer risk
      for only one out of 37 measures or logarithmic transformations thereof is there a
      statistically significant correlation (p<0.05) with radiation- or smoking
      associated risk. CONCLUSIONS: The data used by Tomasetti and Vogelstein are in
      conflict with predictions of a multistage model of carcinogenesis, under the
      assumption of homogeneity of numbers of driver mutations across most cancer
      sites. Their hypothesis that if the extra-risk score for a tissue type is high
      then one would expect that environmental factors would play a relatively more
      important role in that cancer's risk is in conflict with the lack of correlation
      between the extra-risk score and other stem-cell proliferation indices and
      radiation- or smoking-related cancer risk.

PMID- 27031508
TI  - The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary
      Hypertension.
AB  - BACKGROUND: Glycosylated hemoglobin A1c (HbA1c) has been proposed as an
      independent predictor of long-term prognosis in pulmonary arterial hypertension.
      However, the clinical relevance of HbA1c in patients with operable chronic
      thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the
      present study was to investigate the clinical significance of HbA1c as a
      biomarker in CTEPH. METHODS: Prospectively, 102 patients underwent pulmonary
      endarterectomy (PEA) in our national referral center between March 2013 and March
      2014, of which after exclusion 45 patients were analyzed. HbA1c- levels,
      hemodynamic and exercise parameters were analyzed prior and one-year post-PEA.
      RESULTS: 45 patients (BMI: 27.3 +/- 6.0 kg/m2; age: 62.7 +/- 12.3 years) with a
      mean pulmonary arterial pressure (mPAP) of 43.6 +/- 9.4 mmHg, a pulmonary
      vascular resistance (PVR) of 712.1 +/- 520.4 dyn*s/cm5, a cardiac index (CI) of
      2.4 +/- 0.5 l/min/m2 and a mean HbA1c-level of 39.8 +/- 5.6 mmol/mol were
      included. One-year post-PEA pulmonary hemodynamic and functional status
      significantly improved in our cohort. Baseline HbA1c-levels were significantly
      associated with CI, right atrial pressure, peak oxygen uptake and the change of 6
      minute walking distance using linear regression analysis. However, using logistic
      regression analysis baseline HbA1c-levels were not significantly associated with
      residual post-PEA PH. CONCLUSIONS: This is the first prospective study to
      describe an association of HbA1c-levels with pulmonary hemodynamics and exercise
      capacity in operable CTEPH patients. Our preliminary results indicate that in
      these patients impaired glucose metabolism as assessed by HbA1c is of clinical
      significance. However, HbA1c failed as a predictor of the hemodynamic outcome one
      year post-PEA.

PMID- 27031509
TI  - Older Adults with Dementia Are Sedentary for Most of the Day.
AB  - PURPOSE: Self-reported data suggest that older adults with dementia are inactive.
      The purpose of the present study was to objectively assess the physical activity
      (PA) levels of community-dwelling and institutionalized ambulatory patients with
      dementia, and to compare with the PA levels of cognitive healthy older adults.
      METHODS: We used actigraphy to assess the PA levels in institutionalized (n = 83,
      age: 83.0 +/- 7.6, Mini-Mental-State Examination (MMSE): 15.5 +/- 6.5) and
      community-dwelling dementia patients (n = 37, age: 77.3 +/- 5.6, MMSE-score: 20.8
      +/- 4.8), and healthy older adults (n = 26, age: 79.5 +/- 5.6, MMSE-score: 28.2
      +/- 1.6). We characterized PA levels based on the raw data and classified <100
      counts/min as sedentary behavior. RESULTS: Institutionalized dementia patients
      had the lowest daily PA levels (1.69 +/- 1.33 counts/day), spent 72.1% of the day
      sedentary, and were most active between 8:00 and 9:00 am. Institutionalized vs.
      community-dwelling dementia patients had 23.5% lower daily PA levels (difference
      M = 0.52, p = .004) and spent 9.3% longer in sedentariness (difference M = 1.47,
      p = .032). Community-dwelling dementia patients spent 66.0% of the day sedentary
      and were most active between 9:00 to 10:00 am with a second peak between 14:00 to
      15:00. Community-dwelling dementia patients vs healthy older adults' daily PA
      levels and sedentary time were 21.6% lower and 8.9% longer, respectively
      (difference M = 0.61, p = .007; difference M = 1.29, p = .078). CONCLUSIONS:
      Institutionalized and community-dwelling dementia patients are sedentary for most
      of the day and the little PA they perform is of lower intensity compared to their
      healthy peers. Their highest PA peak is when they get out of bed in the morning.
      In addition, it seems that institutionalized living is associated with lower PA
      levels in dementia patients. These are the first results that objectively
      characterize institutionalized as well as community-dwelling dementia patients'
      PA levels and confirm that dementia patients are inactive.

PMID- 27031511
TI  - Uncovering the Roles of Oxygen in Cr(III) Photoredox Catalysis.
AB  - A combined experimental and theoretical investigation aims to elucidate the
      necessary roles of oxygen in photoredox catalysis of radical cation based Diels
      Alder cycloadditions mediated by the first-row transition metal complex
      [Cr(Ph2phen)3](3+), where Ph2phen = bathophenanthroline. We employ a diverse
      array of techniques, including catalysis screening, electrochemistry, time
      resolved spectroscopy, and computational analyses of reaction thermodynamics. Our
      key finding is that oxygen acts as a renewable energy and electron shuttle
      following photoexcitation of the Cr(III) catalyst. First, oxygen quenches the
      excited Cr(3+)* complex; this energy transfer process protects the catalyst from
      decomposition while preserving a synthetically useful 13 MUs excited state and
      produces singlet oxygen. Second, singlet oxygen returns the reduced catalyst to
      the Cr(III) ground state, forming superoxide. Third, the superoxide species
      reduces the Diels-Alder cycloadduct radical cation to the final product and
      reforms oxygen. We compare the results of these studies with those from
      cycloadditions mediated by related Ru(II)-containing complexes and find that the
      distinct reaction pathways are likely part of a unified mechanistic framework
      where the photophysical and photochemical properties of the catalyst species lead
      to oxygen-mediated photocatalysis for the Cr-containing complex but radical chain
      initiation for the Ru congener. These results provide insight into how oxygen can
      participate as a sustainable reagent in photocatalysis.

PMID- 27031510
TI  - Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant
      Nuclear Envelope Phenotype.
AB  - Chromosomal translocations involving the nucleoporin NUP98 have been described in
      several hematopoietic malignancies, in particular acute myeloid leukemia (AML).
      In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C
      terminal region of about 30 different partners, including homeodomain (HD)
      transcription factors. While transcriptional targets of distinct Nup98 chimeras
      related to immortalization are relatively well described, little is known about
      other potential cellular effects of these fusion proteins. By comparing the sub
      nuclear localization of a large number of Nup98 fusions with HD and non-HD
      partners throughout the cell cycle we found that while all Nup98 chimeras were
      nuclear during interphase, only Nup98-HD fusion proteins exhibited a
      characteristic speckled appearance. During mitosis, only Nup98-HD fusions were
      concentrated on chromosomes. Despite the difference in localization, all tested
      Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in
      particular affecting the nuclear lamina and the lamina-associated polypeptide
      2alpha (LAP2alpha). Importantly, such aberrations were not only observed in
      transiently transfected HeLa cells but also in mouse bone marrow cells
      immortalized by Nup98 fusions and in cells derived from leukemia patients
      harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE
      alterations that may contribute to leukemogenesis. 

PMID- 27031512
TI  - Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes.
AB  - Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares
      many features with human type-1 diabetes, there are differences that have cast
      doubt on the immunologic origin of the canine disease. In this study, we examined
      whether peripheral immune responses directed against islet antigens were present
      in dogs with diabetes. Routine diagnostics were used to confirm diabetic status,
      and serum samples from dogs with (N = 15) and without (N = 15) diabetes were
      analyzed for the presence of antibodies against islet antigens (insulin, glutamic
      acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet
      beta-cell zinc cation efflux transporter) using standard radioassays. Interferon
      gamma production from peripheral blood T cells stimulated by porcine insulin and
      by human insulin was tested using Elispot assays. Anti-insulin antibodies were
      detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated
      T cells and incipient insulin-reactive T cells in response to porcine or human
      insulin were identified in non-diabetic dogs and in dogs with diabetes. The data
      show that humoral and cellular anti-insulin immune responses are detectable in
      dogs with diabetes. This in turn provides support for the potential to ethically
      use dogs with diabetes to study the therapeutic potential of antigen-specific
      tolerance. 

PMID- 27031513
TI  - Difference in the late ergosterol biosynthesis between yeast spheroplasts and
      intact cells.
AB  - A comparative study on post-squalene sterol synthesis in intact yeast cells and
      spheroplasts was carried out with strains from three genera (Saccharomyces
      cerevisiae, Schizosaccharomyces pombe, Pichia pastoris) as well as with
      engineered S. cerevisiae cells altered in regard to the late ergosterol synthesis
      pathway. A common outcome of incubation experiments with radioactive acetate was
      that in intact cells the metabolic pathway flows till its specific end product
      (ergosterol and its precursor, depending on the enzyme deficiency), whereas in
      spheroplasts the pathway was stalled some step upstream. For example, in
      spheroplasts from wt strains, non-cyclic triterpenes squalene and oxidosqualene
      accumulated as though the metabolic path was kept from producing steroid-shaped
      molecules different from the end product. Accumulation of non-cyclic triterpenes
      was observed also in spheroplasts from S. cerevisiae cells lacking 3-ketosteroid
      reductase activity, an enzyme belonging to the C4-demethylase complex. When
      production of cyclic triterpenes was compromised by loss or poor functionality of
      oxidosqualene cyclase (EC 5.4.99.7), the difference between intact cells and
      spheroplasts was still remarkable, yet limited to the different
      oxido/dioxidosqualene ratio. The characteristics of spheroplasts as non
      proliferating cells may partially explain the observed differences in post
      squalene pathway from intact cells. We cannot say if the difference in metabolic
      pathways in spheroplasts and intact cells is a rule. We think, however, that it
      is worthwhile to search for an answer, as a wider picture of the points where the
      metabolic pathways are stalled in spheroplasts could provide original ideas about
      the metabolic network in yeast. 

PMID- 27031514
TI  - The Spatial Distribution of Plaque Vulnerabilities in Patients with Acute
      Myocardial Infarction.
AB  - OBJECTIVE: Although the plaque characteristics have been recognized in patients
      with acute myocardial infarction (AMI), the plaque spatial distribution is not
      well clarified. Using color-mapping intravascular ultrasound (iMAP-IVUS), we
      examined culprit lesions to clarify plaque morphology, composition and spatial
      distribution of the sites of potential vulnerability. METHODS: Sixty-eight
      culprit lesions in 64 consecutive AMI patients who underwent angiography and IVUS
      examinations before intervention were analyzed. Plaque morphology and composition
      were quantified with iMAP-IVUS. The spatial distribution of the sites of
      potential vulnerability was assessed with longitudinal reconstruction of the
      consecutive IVUS images. The plaque characteristics were also compared between
      ruptured and non-ruptured lesions, and between totally occlusive (TO) and non-TO
      lesions. RESULTS: The sites with maximum necrotic area (maxNA), maximum plaque
      burden (maxPB) and most severely narrowed (minimal luminal area, MLA) were
      recognized vulnerability. In the majority of cases, maxNA sites were proximal to
      the maxPB sites, and MLA sites were distal to the maxNA and maxPB sites. Ruptures
      usually occurred close to maxNA sites and proximal to maxPB and MLA sites. The
      average distance from the site of rupture to the maxNA site was 0.33 +/- 4.04 mm.
      Ruptured lesions showed significant vessel remodeling, greater plaque volume, and
      greater lipidic volume compared to those of non-ruptured lesions. Both the length
      and plaque burden (PB) of TO lesions were greater than those of non-TO lesions.
      CONCLUSIONS: Instead of overlapping on maxPB sites, most maxNA sites are proximal
      to the maxPB sites and are the sites most likely to rupture. Plaque morphology
      and composition play critical roles in plaque rupture and coronary occlusion.

PMID- 27031515
TI  - Costs Associated with Malaria in Pregnancy in the Brazilian Amazon, a Low Endemic
      Area Where Plasmodium vivax Predominates.
AB  - BACKGROUND: Information on costs associated with malaria in pregnancy (MiP) in
      low transmission areas where Plasmodium vivax predominates is so far missing.
      This study estimates health system and patient costs of MiP in the Brazilian
      Amazon. METHODS/PRINCIPAL FINDINGS: Between January 2011 and March 2012 patient
      costs for the treatment of MiP were collected through an exit survey at a
      tertiary referral hospital and at a primary health care centre in the Manaus
      metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with
      malaria were interviewed after an outpatient consultation or at discharge after
      admission. Seventy-three interviews were included in the analysis. Ninety-six
      percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In
      2010, the total median costs from the patient perspective were estimated at US
      $45.91 and US $216.29 for an outpatient consultation and an admission,
      respectively. When multiple P. vivax infections during the same pregnancy were
      considered, patient costs increased up to US $335.85, representing the costs of
      an admission plus an outpatient consultation. Provider direct and overhead cost
      data were obtained from several sources. The provider cost associated with an
      outpatient case, which includes several consultations at the tertiary hospital
      was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum
      malaria episode. The cost of an inpatient day and average admission of 3 days was
      US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis
      and treatment of all malaria cases reported in pregnant women in Manaus in 2010
      (N = 364) were US $17,038.50, of which 92.4% (US$ 15,741.14) due to P. vivax
      infection. CONCLUSION: Despite being an area of low risk malaria transmission,
      MiP is responsible for a significant economic burden in Manaus. Especially when
      multiple infections are considered, costs associated with P. vivax are higher
      than costs associated with P. falciparum. The information generated may help
      health policy decisions for the current control and future elimination of malaria
      in the area.

PMID- 27031516
TI  - Obstetricians' Opinions of the Optimal Caesarean Rate: A Global Survey.
AB  - BACKGROUND: The debate surrounding the optimal caesarean rate has been ongoing
      for several decades, with the WHO recommending an "acceptable" rate of 5-15%
      since 1997, despite a weak evidence base. Global expert opinion from obstetric
      care providers on the optimal caesarean rate has not been documented. The
      objective of this study was to examine providers' opinions of the optimal
      caesarean rate worldwide, among all deliveries and within specific sub-groups of
      deliveries. METHODS: A global online survey of medical doctors who had performed
      at least one caesarean in the last five years was conducted between August 2013
      and January 2014. Respondents were asked to report their opinion of the optimal
      caesarean rate--defined as the caesarean rate that would minimise poor maternal
      and perinatal outcomes--at the population level and within specific sub-groups of
      deliveries (including women with demographic and clinical risk factors for
      caesareans). Median reported optimal rates and corresponding inter-quartile
      ranges (IQRs) were calculated for the sample, and stratified according to
      national caesarean rate, institutional caesarean rate, facility level, and
      respondent characteristics. RESULTS: Responses were collected from 1,057 medical
      doctors from 96 countries. The median reported optimal caesarean rate was 20%
      (IQR: 15-30%) for all deliveries. Providers in private for-profit facilities and
      in facilities with high institutional rates reported optimal rates of 30% or
      above, while those in Europe, in public facilities and in facilities with low
      institutional rates reported rates of 15% or less. Reported optimal rates were
      lowest among low-risk deliveries and highest for Absolute Maternal Indications
      (AMIs), with wide IQRs observed for most categories other than AMIs. CONCLUSIONS:
      Three-quarters of respondents reported an optimal caesarean rate above the WHO
      15% upper threshold. There was substantial variation in responses, highlighting a
      lack of consensus around which women are in need of a caesarean among obstetric
      care providers worldwide.

PMID- 27031517
TI  - Assessment of Rheumatoid Arthritis Quality Process Measures and Associated Costs.
AB  - The objective was to examine the relationship between health care costs and
      quality in rheumatoid arthritis (RA). Administrative claims were used to
      calculate 8 process measures for the treatment of RA. Associated health care
      costs were calculated for members who achieved or did not achieve each of the
      measures. Medical, pharmacy, and laboratory claims for RA patients (International
      Classification of Diseases, Ninth Revision, Clinical Modification 714.x) were
      extracted from the Optum Clinformatics Datamart database for 2011. Individuals
      were predominately female and in their mid-fifties. Measure achievement ranged
      from 55.9% to 80.8%. The mean cost of care for members meeting the measure was
      $18,644; members who did not meet the measures had a mean cost of $14,973.
      Primary cost drivers were pharmacy and office expenses, accounting for 42.4% and
      26.3% of total costs, respectively. Regression analyses revealed statistically
      significant associations between biologic usage, which was more prevalent in
      groups attaining measures, and total expenditure across all measures (Ps <
      0.001). Pharmacy costs were similar between both groups. Individuals meeting the
      measures had a higher proportion of costs accounted for by office visits; those
      not meeting the measures had a higher proportion of costs from inpatient and
      outpatient visits. These findings suggest that increased quality may lead to
      lower inpatient and outpatient hospital costs. Yet, the overall cost of RA care
      is likely to remain high because of intensive pharmacotherapy regimens.

PMID- 27031522
TI  - Correction: Exome Sequencing of Index Patients with Retinal Dystrophies as a Tool
      for Molecular Diagnosis.

PMID- 27031521
TI  - High Prevalence of New Delhi Metallo-beta-Lactamase-1 (NDM-1) Producers among
      Carbapenem-Resistant Enterobacteriaceae in Kuwait.
AB  - The aim of the study was to determine the prevalence of New Delhi metallo-beta
      lactamase-1 (NDM-1) producing Enterobacteriaceae in Kuwait over a one year
      period. Consecutive Enterobacteriaceae isolates with reduced susceptibility to
      carbapenems were collected from four government hospitals in Kuwait from January
      December 2014. Their susceptibility to 18 antibiotics was performed by
      determining the minimum inhibitory concentration. Isolates resistant to
      carbapenems were tested by PCR for resistant genes. Finger printing of the
      positive isolates was done by DiversiLab(r). Clinical data of patients harboring
      NDM-1 positive isolates were analyzed. A total of 764 clinically significant
      Enterobacteriaceae isolates were studied. Of these, 61 (8%) were carbapenem
      resistant. Twenty one out of these 61 (34.4%) were NDM-1-producers. All patients
      positive for NDM-1-carrying bacteria were hospitalized. About half were females
      (11/21 [52.3%]), average age was 53.3 years and the majority were Kuwaitis (14/21
      [66.6%]). Six patients (28.5%) gave a history of travel or healthcare contact in
      an endemic area. Mortality rate was relatively high (28.6%). The predominant
      organism was Klebsiella pneumoniae (14 [66.6%]) followed by E. coli (4 [19%]).
      All NDM-1-positive isolates were resistant to meropenem, ertapenem, cefotaxime,
      cefoxitin and ampicillin, while 95.2% were resistant to imipenem, cefepime, and
      piperacillin-tazobactam. They were multidrug resistant including resistance to
      tigecycline, but 90% remained susceptible to colistin. About two-thirds of
      isolates (61.9%) co-produced-extended spectrum beta-lactamases. During the study
      period, an outbreak of NDM-1 positive K. pneumoniae occurred in one hospital
      involving 3 patients confirmed by DiversiLab(r) analysis. In conclusion, NDM-1
      producing Enterobacteriaceae is a growing healthcare problem with increasing
      prevalence in Kuwait, especially in hospitalized patients, leaving few
      therapeutic options. A high prevalence of NDM-1 necessitates the implementation
      of strict infection control to prevent the spread of these organisms. 

PMID- 27031523
TI  - Spatial Coding as a Function of Handedness and Responding Hand: Theoretical and
      Methodological Implications.
AB  - The Simon effect shows that choice reactions are faster if the location of the
      stimulus and the response correspond, even when stimulus location is task
      irrelevant. The Simon effect raises the question of what factors influence
      spatial coding. Until now, the effects of handedness, responding hand, and visual
      field were addressed in separate studies that used bimanual and unimanual tasks,
      providing inconclusive results. Here we aimed to close this empirical gap by
      looking at the effects of these variables in the same study. We used a unimanual
      version of a Simon task with four groups of participants: left-handed and right
      handed, responding with the dominant or nondominant hand. Our results show that
      the Simon effect is substantially reduced in the field of the responding hand for
      all groups of participants, except for left-handed individuals responding with
      the left-hand. These findings highlight the importance of attention mechanisms in
      stimulus-response coding. They reflect that stimulus-response interference is
      influenced by hierarchical activation of response units. At a practical level,
      these findings call for a number of methodological considerations (e.g.,
      handedness, responding hand, and visual field) when using stimulus-response
      conflict to address spatial coding and cognitive control functions in
      neurological populations. 

PMID- 27031524
TI  - Prediction of Dengue Outbreaks Based on Disease Surveillance and Meteorological
      Data.
AB  - Research is needed to create early warnings of dengue outbreaks to inform
      stakeholders and control the disease. This analysis composes of a comparative set
      of prediction models including only meteorological variables; only lag variables
      of disease surveillance; as well as combinations of meteorological and lag
      disease surveillance variables. Generalized linear regression models were used to
      fit relationships between the predictor variables and the dengue surveillance
      data as outcome variable on the basis of data from 2001 to 2010. Data from 2011
      to 2013 were used for external validation purposed of prediction accuracy of the
      model. Model fit were evaluated based on prediction performance in terms of
      detecting epidemics, and for number of predicted cases according to RMSE and
      SRMSE, as well as AIC. An optimal combination of meteorology and autoregressive
      lag terms of dengue counts in the past were identified best in predicting dengue
      incidence and the occurrence of dengue epidemics. Past data on disease
      surveillance, as predictor alone, visually gave reasonably accurate results for
      outbreak periods, but not for non-outbreaks periods. A combination of
      surveillance and meteorological data including lag patterns up to a few years in
      the past showed most predictive of dengue incidence and occurrence in Yogyakarta,
      Indonesia. The external validation showed poorer results than the internal
      validation, but still showed skill in detecting outbreaks up to two months ahead.
      Prior studies support the fact that past meteorology and surveillance data can be
      predictive of dengue. However, to a less extent has prior research shown how the
      longer-term past disease incidence data, up to years, can play a role in
      predicting outbreaks in the coming years, possibly indicating cross-immunity
      status of the population. 

PMID- 27031526
TI  - SCLERAL IMBRICATION COMBINED WITH PARS PLANA VITRECTOMY WITHOUT INTERNAL LIMITING
      MEMBRANE PEELING FOR MYOPIC SCHISIS.
AB  - PURPOSE: We investigated whether scleral imbrication combined with pars plana
      vitrectomy without internal limiting membrane peeling would be effective in
      treating eyes with myopic macular schisis. METHODS: In this retrospective,
      interventional case series, 8 eyes of 8 patients with myopic retinoschisis
      without a macular hole were studied. Scleral imbrication was done with 6-mm-wide
      mattress sutures placed at the temporal quadrants. Pars plana vitrectomy and
      removal of the vitreous cortex were performed, but the internal limiting membrane
      was not removed. The best-corrected visual acuity was measured, and the retinal
      morphology was determined by spectral-domain optical coherence tomography before
      and at 6 and 12 months postoperatively. RESULTS: The mean age of the subjects was
      67.1 years. The best-corrected visual acuity improved from 0.71 +/- 0.25 to 0.36
      +/- 0.19 logarithm of the minimum angle of resolution units (Snellen equivalent:
      from 20/100 to 20/50) at 12 months (P = 0.028). The axial length was shortened
      from 29.5 +/- 1.7 to 28.5 +/- 2.5 at 12 months (P = 0.012). The central foveal
      thickness decreased from 540 +/- 171 MUm to 170 +/- 85 MUm at 12 months (P =
      0.012). In the 6 macular-detached eyes, 5 eyes (83%) had a complete resolution.
      The curvature of posterior eye wall was flatter at 12 months (P = 0.049). No
      retinal complications were observed. CONCLUSION: Scleral imbrication combined
      with pars plana vitrectomy can be an effective method of treating myopic schisis.

PMID- 27031525
TI  - Inhibition of p38 Mitogen-Activated Protein Kinase Enhances the Apoptosis Induced
      by Oxidized Low-Density Lipoprotein in Endothelial Progenitor Cells.
AB  - Oxidized low-density lipoprotein (oxLDL) is an important risk factor in the
      development of atherosclerosis. oxLDL has been shown to decrease endothelial
      progenitor cell (EPC) number by inducing apoptosis. p38 mitogen-activated protein
      kinase (MAPK) was shown to be activated by oxLDL and participated in the
      regulation of EPC number and function. However, the role of p38 remains unknown.
      Here, we show that oxLDL-induced p38 phosphorylation in EPCs is time and dose
      dependent. Treatment with antioxidant N-acetyl cysteine restored oxLDL-induced
      p38 phosphorylation to basal levels. LOX-1-blocking antibody also significantly
      decreased oxLDL-induced p38 phosphorylation. Interestingly, TUNEL staining showed
      that pretreatment with the p38 inhibitor SB203580 further increased oxLDL-induced
      apoptosis in EPCs. In accordance with these findings, pretreatment with SB203580
      further attenuated Akt phosphorylation in EPCs challenged with oxLDL, indicating
      an interaction between Akt and p38 MAPK pathways. In agreement, inhibition of p38
      MAPK further attenuated Akt phosphorylation and increased apoptosis in EPCs
      isolated from hypercholesterolemic ApoE-/- mice. In conclusion, p38 MAPK serves
      as an anti-apoptotic pathway by supporting Akt activity when EPCs are challenged
      with oxLDL.

PMID- 27031527
TI  - Pyramidal-Shaped Residual Subretinal Fluid at Fovea After Intravitreal Injection
      of Perfluoro-n-Octane in Eyes With Fovea-Off Rhegmatogenous Retinal Detachment.

PMID- 27031528
TI  - EXTERNAL BEAM RADIATION FOR CHOROIDAL LYMPHOMA: Efficacy and Complications.
AB  - PURPOSE: To determine the efficacy and safety of external beam radiation for
      treatment of choroidal lymphoma (CL). DESIGN: Retrospective case series.
      PARTICIPANTS: Twenty-five eyes of 24 patients with CL treated with external beam
      radiation. METHOD: Review of medical records. MAIN OUTCOME MEASURES: Tumor
      control, visual acuity, and radiation complications. RESULTS: The mean age of the
      patients was 62 years (median, 65; range, 32-89 years). Only 2 patients (8%) had
      a history of systemic lymphoma. The most common symptom was painless blurred
      vision in 14 eyes (58%) and the mean duration of ocular symptoms was 12 months
      (median, 7; range, 1-36 months). Initial best-corrected visual acuity was 20/40
      or better in 10 eyes (40%), 20/50 to 20/150 in 12 eyes (48%), and 20/200 or less
      in the other 3 eyes (12%). The fovea was involved by the CL in 16 eyes (64%).
      Mean tumor thickness was 3.1 mm (median, 3.0; range 1.1-6.3 mm). Anterior and
      posterior transscleral extension of CL were present in 15 (60%) and 14 eyes
      (56%), respectively. All patients, except 3 (13%), had some form of ocular biopsy
      confirming the diagnosis of ocular lymphoma. The mean total radiation dose was
      2,867 cGy (median, 3,000; range, 1,200-3,600 cGy). At final examination, after a
      mean follow-up period of 58 months (median, 35; range, 13-228 months), 18 eyes
      (72%) showed complete regression of CL and 7 eyes (28%) showed partial
      regression. All eyes (100%) with initial serous retinal detachment (14 eyes),
      subfoveal fluid (8 eyes), and macular edema (5 eyes) achieved complete resolution
      of subretinal or intraretinal fluid after treatment. Recurrence of CL after
      initial partial response developed in only 1 eye (4%). Compared with the initial
      evaluation, final best-corrected visual acuity had increased in 11 (44%), was
      stable in 8 (32%), and had decreased in 6 eyes (24%). Only 2 eyes (8%) showed
      signs of mild nonproliferative retinopathy. CONCLUSION: In this study, external
      beam radiation was an effective and safe modality for treatment of CL, achieving
      long-term tumor regression in 96% and stable or improved vision in 76% after mean
      follow-up period of 6 years.

PMID- 27031529
TI  - Novel Technique for Subretinal Injection Using Local Removal of the Internal
      Limiting Membrane.

PMID- 27031530
TI  - Actibacterium ureilyticum sp. nov., isolated from seawater.
AB  - A polyphasic approach was used to characterize a novel marine bacterial strain,
      designated LS-811T, isolated from seawater of the South China Sea (Taiwan). Cells
      of strain LS-811Twere Gram-staining negative, aerobic and rod-shaped with polar
      flagella. The 16S rRNA gene sequence analysis of strain LS-811T showed highest
      sequence similarity to Actibacterium mucosum (96.5 %) and Actibacterium
      atlanticum (95.6 %), and lower sequence similarity (<96.0 %) to members of all
      other related genera. Strain LS-811Twas able to grow at 15-40  degrees C and pH
      5.0-9.0. The quinone system was ubiquinone (Q-10), and the DNA G+C content was
      60.1 mol%. The major fatty acids (>5 %) found in strain LS-811T were C18 : 0, C10
      : 0 3-OH, C19 : 0 cyclo omega8c and C18 : 1omega7c/C18 : 1omega6c. The major
      polar lipid profile consisted of glycolipids, phosphatidylglycerol and one
      unidentified aminolipid. Based on the distinct phylogenetic, phenotypic and
      chemotaxonomic traits together with results of comparative 16S rRNA gene sequence
      analysis, strain LS-811T is considered to represent a novel species in the genus
      Actibacterium, for which the name Actibacterium ureilyticum sp. nov. is proposed.
      The type strain is LS-811T (=BCRC 80823T=JCM 30681T). 

PMID- 27031531
TI  - Streptosporangium jiaoheense sp. nov. and Streptosporangium taraxaci sp. nov.,
      actinobacteria isolated from soil and dandelion root (Taraxacum mongolicum Hand.
      Mazz.).
AB  - Two novel actinobacteria, designated strains NEAU-Jh1-4T and NEAU-Wp2-0T, were
      isolated from muddy soil collected from a riverbank in Jiaohe and a dandelion
      root collected from Harbin, respectively. A polyphasic study was carried out to
      establish the taxonomic positions of these two strains. The phylogenetic analysis
      based on the 16S rRNA gene sequences of strains NEAU-Jh1-4T and NEAU-Wp2-0T
      indicated that strain NEAU-Jh1-4T clustered with Streptosporangium nanhuense NEAU
      NH11T (99.32 % 16S rRNA gene sequence similarity), Streptosporangium purpuratum
      CY-15110T (98.30 %) and Streptosporangium yunnanense CY-11007T (97.95 %) and
      strain NEAU-Wp2-0T clustered with 'Streptosporangium sonchi  ' NEAU-QS7 (99.39
      %), 'Streptosporangium kronopolitis' NEAU-ML10 (99.26 %), 'Streptosporangium
      shengliense' NEAU-GH7 (98.85 %) and Streptosporangium longisporum DSM 43180T
      (98.69 %). Moreover, morphological and chemotaxonomic properties of the two
      isolates also confirmed their affiliation to the genus Streptosporangium.
      However, the low level of DNA-DNA hybridization and some phenotypic
      characteristics allowed the isolates to be differentiated from the most closely
      related species. Therefore, it is proposed that strains NEAU-Jh1-4T and NEAU-Wp2
      0T represent two novel species of the genus Streptosporangium, for which the name
      Streptosporangium jiaoheense sp. nov. and Streptosporangium taraxaci sp. nov. are
      proposed. The type strains are NEAU-Jh1-4T (=CGMCC 4.7213T=JCM 30348T) and NEAU
      Wp2-0T (=CGMCC 4.7217T=JCM 30349T), respectively. 

PMID- 27031532
TI  - Asthma management in New York City schools: A classroom teacher perspective.
AB  - OBJECTIVE: Classroom teachers play an important role in facilitating asthma
      management in school but little is known about their perspectives around asthma
      management. We examined the perspectives of classroom teachers around barriers to
      school asthma management. METHODS: We conducted key informant interviews with 21
      inner-city classroom teachers from 3rd to 5th grades in 10 Bronx, New York
      elementary schools. Sampling continued until thematic saturation was reached.
      Interviews were recorded, transcribed, and independently coded for common themes.
      We used thematic and content review to analyze interview data. RESULTS: Seven
      themes representing teachers' perspectives on in-school asthma management
      emerged: (1) the problematic process of identifying students with asthma; (2)
      poor familiarity with the city health department's asthma initiative and poor
      general knowledge of school policies on asthma management; (3) lack of competency
      in managing an acute asthma attack in the classroom and poor recognition of
      symptoms of an asthma attack; (4) lack of confidence in dealing with a
      hypothetical asthma attack in the classroom; (5) lack of quick access to asthma
      medication in school; (6) limited communication between school staff; and (7)
      enthusiasm about learning more about asthma management. CONCLUSIONS: Our results
      revealed several barriers contributing to suboptimal in-school asthma management:
      ineffective ways of identifying students with asthma, lack of teacher knowledge
      of guidelines on asthma management, lack of comfort in managing students' asthma,
      inadequate access to asthma medication in school, and limited communication
      between school staff. These issues should be considered in the design of
      interventions to improve in-school asthma management.

PMID- 27031533
TI  - Effectiveness of a Staff Promoted Wellness Program to Improve Health in Residents
      of a Mental Health Long-Term Care Facility.
AB  - The current study describes physical and mental health outcomes during a health
      promotion program for individuals with serious mental illness (SMI). A sample of
      43 adults in a long-term residential facility volunteered for an individualized,
      healthy lifestyle program designed to promote physical activity and combat
      premature mortality among individuals with SMI. Nurses and residential counselors
      were trained in the program and encouraged to work collaboratively with the
      program's personal trainers. Weekly nutrition and activity logs were obtained
      over the year-long evaluation. Assessments of physical and psychological health
      indicators were collected quarterly. Qualitative data through focus groups
      described staff experience. Self-report of moderate and vigorous physical
      activity improved over time as did fitness level as measured through a walking
      challenge (p = .001). Significant decreases in weight (p < .001), BMI (p = .001),
      and total cholesterol (p < .001) were observed from baseline through 12 months.
      Mean recovery scores (RMQ) were significantly higher between baseline and all
      time points (p < .001). Participants reported decreasing levels of depression
      (PHQ-9) by the 12-month time point (p < .001). Staff encouraged participation in
      physical activity and observed improved motivation and socialization among
      participants. A health promotion program with participation encouraged by health
      care staff is effective for increasing physical activity and improving physical
      and mental health outcomes in individuals with SMI in long-term residential care.

PMID- 27031534
TI  - Prophylaxis of venous thromboembolism in cancer patients.
AB  - Venous thromboembolism (VTE) is an independent prognostic factor and the second
      leading cause of death in cancer patients. VTE is however a largely preventable
      disease when thromboprophylaxis is appropriately used. As recommended worldwide
      by international Clinical Practice Guidelines, cancer patients undergoing surgery
      or hospitalization for acute medical illness or with reduced mobility should
      benefit from thromboprophylaxis, in the absence of bleeding or other
      contraindications to anticoagulants. Thromboprophylaxis in cancer outpatients
      receiving systemic therapies is still under debate, except for pancreatic
      ambulatory cancer patients where prophylaxis confers a sustained reduction in
      VTE. Numerous strategies are currently developed to improve VTE prophylaxis
      practices in cancer patients, and to elucidate the best appropriate anticoagulant
      regimen for each individual cancer patient. 

PMID- 27031535
TI  - Rhabdomyolysis in adolescent athletes: review of cases.
AB  - Rhabdomyolysis is a syndrome characterized by muscle pain, weakness and
      myoglobinuria and ranges in severity from asymptomatic to life threatening with
      acute kidney failure. While a common condition in adult populations, it is
      understudied in pediatrics and the majority of adolescent cases are likely
      exercise-induced, caused by strenuous exercise in athletes. Recently, in our
      pediatric sports medicine practice, we have seen numerous cases of late
      adolescent high school athletes who present with severe muscle pain and were
      found to have elevated creatine kinase levels. The cases review potential
      contributing factors including characteristics of the workout, use of
      supplements, caffeine, medication, and metabolic or genetic predisposition.
      Treatment for exercised-induced rhabdomyolysis rarely requires more than
      rehydration. Return to play should be progressive, individualized, and include
      acclimatization and monitoring of hydration status, though guidelines require
      further review. 

PMID- 27031536
TI  - Electrostatic Assembly Preparation of High-Toughness Zirconium Diboride-Based
      Ceramic Composites with Enhanced Thermal Shock Resistance Performance.
AB  - The central problem of using ceramic as a structural material is its brittleness,
      which associated with rigid covalent or ionic bonds. Whiskers or fibers of strong
      ceramics such as silicon carbide (SiC) or silicon nitride (Si3N4) are widely
      embedded in a ceramic matrix to improve the strength and toughness. The
      incorporation of these insulating fillers can impede the thermal flow in ceramic
      matrix, thus decrease its thermal shock resistance that is required in some
      practical applications. Here we demonstrate that the toughness and thermal shock
      resistance of zirconium diboride (ZrB2)/SiC composites can be improved
      simultaneously by introducing graphene into composites via electrostatic assembly
      and subsequent sintering treatment. The incorporated graphene creates weak
      interfaces of grain boundaries (GBs) and optimal thermal conductance paths inside
      composites. In comparison to pristine ZrB2-SiC composites, the toughness of
      (2.0%) ZrB2-SiC/graphene composites exhibited a 61% increasing (from 4.3 to 6.93
      MPa.m(1/2)) after spark plasma sintering (SPS); the retained strength after
      thermal shock increased as high as 74.8% at 400  degrees C and 304.4% at 500 
      degrees C. Present work presents an important guideline for producing high
      toughness ceramic-based composites with enhanced thermal shock properties.

PMID- 27031537
TI  - Uprooting an abscisic acid paradigm: Shoots are the primary source.
AB  - In the past, a conventional wisdom has been that abscisic acid (ABA) is a xylem
      transported hormone that is synthesized in the roots, while acting in the shoot
      to close stomata in response to a decrease in plant water status. Now, however,
      evidence from two studies, which we have conducted independently, challenges this
      root-sourced ABA paradigm. We show that foliage-derived ABA has a major influence
      over root development and that leaves are the predominant location for ABA
      biosynthesis during drought stress.

PMID- 27031538
TI  - Ipilimumab-induced acute generalized exanthematous pustulosis in a patient with
      metastatic melanoma.
AB  - Ipilimumab is a new anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody
      that stimulates the immune response against melanoma. A 50-year-old man received
      ipilimumab for metastatic melanoma as part of a clinical trial. Two weeks after
      drug initiation, he developed a widespread oedematous erythema with sterile
      pustules. The histological examination showed subcorneal pustulosis formation
      with eosinophils. The clinical-pathological correlation was consistent with acute
      generalized exanthematous pustulosis. The symptoms resolved within 25 days after
      discontinuation of ipilimumab. We suspect that neutrophilic accumulation under
      the epidermis in this patient is a phenomenon similar to intraepithelial
      neutrophils aggregating on the surface epithelium over laminar propria in
      ipilimumab-induced colitis. To our knowledge, this is the first reported case of
      acute generalized exanthematous pustulosis associated with ipilimumab use in
      metastatic melanoma patients.

PMID- 27031539
TI  - Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related
      adverse event in patients treated with anti-programmed cell death 1 antibodies.
AB  - Anti-programmed cell death 1 (anti-PD1) antibodies such as pembrolizumab have
      shown improved progression-free and overall survival in patients with advanced
      melanoma. Of 124 patients reviewed in Westmead Hospital from May 2012 to November
      2015, treated with pembrolizumab for advanced melanoma, we encountered three
      cases of bullous pemphigoid (BP). We have previously reported a case of BP. In
      two recent cases, BP was diagnosed early and treated promptly with potent topical
      or oral steroid. Patients on anti-PD1 antibodies are at a higher risk of
      developing cutaneous immune-related adverse events such as lichenoid reactions,
      eczema and vitiligo. No cases of BP were encountered in the previously published
      cohort of 260 melanoma patients treated with BRAF inhibitors; as such, it appears
      that BP is associated with anti-PD1 treatment rather than metastatic melanoma. BP
      appears to be another immune-related adverse event, and clinicians should have a
      low threshold for performing cutaneous biopsies and immunofluorescence studies in
      patients on anti-PD1 therapies.

PMID- 27031540
TI  - Comparison of femtosecond and excimer laser platforms available for corneal
      refractive surgery.
AB  - PURPOSE OF REVIEW: The evolution of laser technology has left today's refractive
      surgeon with a choice between multiple laser platforms. The purpose of this
      review is to compare currently available femtosecond and excimer laser platforms,
      providing a summary of current evidence. RECENT FINDINGS: Femtosecond lasers
      create LASIK flaps with better accuracy, uniformity, and predictability than
      mechanical microkeratomes. Newer higher-frequency femtosecond platforms elicit
      less inflammation, producing better visual outcomes. SMILE achieved similar
      safety, efficacy, and predictability as LASIK with greater preservation of
      corneal nerves and biomechanical strength. The emergence of wavefront technology
      has resulted in improved excimer laser treatments. Comparisons of wavefront
      guided and wavefront-optimized treatments suggest that there is an advantage to
      using wavefront-guided platforms in terms of visual acuity and quality of vision.
      Topography-guided ablations are another well tolerated and effective option,
      especially in eyes with highly irregular corneas. SUMMARY: Advances in
      femtosecond and excimer laser technology have not only improved the safety and
      efficacy of refractive procedures, but have also led to the development of
      promising new treatment modalities, such as SMILE and the use of wavefront-guided
      and topography-guided ablation. Future studies and continued technological
      progress will help to better define the optimal use of these treatment platforms.

PMID- 27031541
TI  - A Woman With Bilateral Cervical Lymphadenopathy.

PMID- 27031542
TI  - Liquid Biopsy in Metastasized Breast Cancer as Basis for Treatment Decisions.
AB  - According to current guidelines, the additional biopsy of breast cancer
      metastases to analyze the receptor status for phenotype assessment is
      recommended. However, due to clinical difficulties in performing biopsies of
      metastatic lesions, the phenotype of the primary tumor most often determines the
      treatment decisions in metastatic breast cancer. Liquid biopsy allows the
      analysis of several circulating biomarkers like circulating tumor cells (CTCs) or
      circulating tumor DNA (ctDNA) in peripheral blood samples of cancer patients.
      Thus, it is an elegant and easily practicable technique that delivers information
      on the current disease status. Determination of the CTC phenotype regarding the
      hormone receptor and human epidermal growth factor receptor 2 (HER2) status might
      replace additional tissue biopsy for planning further therapy strategies. Liquid
      biopsy is a crucial step towards a more individualized cancer therapy. In
      contrast to the conventional concept of tissue biopsy, it offers an easy, less
      invasive acquisition of biomaterial. In addition, it allows multiple repetitions
      and real-time monitoring of metastasized disease in the clinical routine.
      However, the clinical utility of liquid biopsy still needs to be evaluated. 

PMID- 27031543
TI  - Contribution Levels of Intrinsic Risk Factors to the Management of Patients with
      Plantar Heel Pain A Pilot Study.
AB  - BACKGROUND: Of all of the lower-extremity injuries with multifactorial causes,
      heel pain represents the most frequent reason for visits to health-care
      professionals. Managing patients with heel pain can be very difficult. The
      purpose of this research was to identify key variables that can influence foot
      health in patients with heel pain. METHODS: A cross-sectional observational study
      was performed with 62 participants recruited from the Educational Welfare Unit of
      the University of Malaga, Malaga, Spain. Therapists, blinded for the study,
      acquired the anthropometric information and the Foot Posture Index, and
      participants completed the Foot Health Status Questionnaire. RESULTS: The most
      significant results reveal that there is a moderate relationship between clinical
      variables such as footwear and Foot Health Status Questionnaire commands such as
      Shoe (r = 0.515; P < .001). The most significant model domain was General Health
      (P < .001), with the highest determination coefficient (beta not standard =
      34.05). The most significant predictable variable was body mass index (-0.110).
      CONCLUSIONS: The variables that can help us manage clinical patients with heel
      pain are age, body mass index, footwear, and Foot Posture Index (left foot).

PMID- 27031544
TI  - Extracorporeal Shockwave Therapy in Patients with Morton's Neuroma A Randomized,
      Placebo-Controlled Trial.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of extracorporeal
      shockwave therapy (ESWT) for the treatment of Morton's neuroma by measuring
      changes in patient pain, function, and neuroma size. METHODS: Patients with
      Morton's neuroma were randomly assigned to either the ESWT group or the sham
      stimulation group. Outcome measures, including visual analog scale (VAS) and
      American Orthopaedic Foot and Ankle Society lesser toes (AOFAS) scores, were
      assessed at baseline and 1 and 4 weeks after treatment. The Johnson satisfaction
      test was also performed 1 and 4 weeks after treatment. The neuroma diameter was
      measured using ultrasonography at baseline and 4 weeks after treatment. RESULTS:
      Patients receiving ESWT exhibited significantly decreased VAS scores 1 and 4
      weeks after treatment relative to baseline, and AOFAS scores were significantly
      improved 4 weeks after treatment relative to baseline. In the sham stimulation
      group, VAS and AOFAS scores showed no significant changes at any time after
      treatment. Neither group showed significant changes in Johnson satisfaction test
      results or neuroma diameter. CONCLUSIONS: These results suggest that ESWT may
      reduce pain in patients with Morton's neuroma.

PMID- 27031545
TI  - Weil and Dorsal Closing Wedge Osteotomy for Freiberg's Disease.
AB  - BACKGROUND: Weil osteotomy is a type of distal osteotomy for the treatment of
      lesser metatarsalgia by shortening the metatarsal length. We applied Weil and
      dorsal closing wedge osteotomy for the treatment of Freiberg's disease. METHODS:
      Between September 1, 2006, and December 31, 2011, we performed Weil and dorsal
      closing wedge osteotomy of the second metatarsal in 15 feet of 15 patients (12
      women, three men) diagnosed as having Freiberg's disease. The mean patient age
      was 29 years (range, 19-51 years), and mean follow-up was 47 months (range, 36-72
      months). Postoperative shortening of the metatarsal length was measured by
      comparing preoperative and postoperative radiographs. Visual analog scale scores,
      American Orthopedic Foot and Ankle Society lesser metatarsophalangeal
      interphalangeal scores, and the passive range of motion of the
      metatarsophalangeal joint were evaluated at 24 months. RESULTS: The mean
      postoperative shortening of the metatarsal length was 3.2 mm. The mean visual
      analog scale and American Orthopedic Foot and Ankle Society scores were 7.2 and
      52.4 points preoperatively and 2.1 and 78.2 points at 24 months, respectively (P
      < .05). The mean range of motion of the metatarsophalangeal joint increased from
      29.4 degrees  preoperatively to 46.5 degrees  postoperatively (P < .05). Various
      degrees of remodeling were observed at the dorsum of the metatarsal head at 24
      months. CONCLUSIONS: Weil and dorsal closing wedge osteotomy of the metatarsal
      seems to be effective for treating Freiberg's disease. It improves pain and
      function in terms of shortening the metatarsal length and restoring the
      metatarsophalangeal joint.

PMID- 27031546
TI  - The Influence of Running on Foot Posture and In-Shoe Plantar Pressures.
AB  - BACKGROUND: Running can be considered a high-impact practice, and most people
      practicing continuous running experience lower-limb injuries. The aim of this
      study was to determine the influence of 45 min of running on foot posture and
      plantar pressures. METHODS: The sample comprised 116 healthy adults (92 men and
      24 women) with no foot-related injuries. The mean +/- SD age of the participants
      was 28.31 +/- 6.01 years; body mass index, 23.45 +/- 1.96; and training time,
      11.02 +/- 4.22 h/wk. Outcome measures were collected before and after 45 min of
      running at an average speed of 12 km/h, and included the Foot Posture Index (FPI)
      and a baropodometric analysis. RESULTS: The results show that foot posture can be
      modified after 45 min of running. The mean +/- SD FPI changed from 6.15 +/- 2.61
      to 4.86 +/- 2.65 (P < .001). Significant decreases in mean plantar pressures in
      the external, internal, rearfoot, and forefoot edges were found after 45 min of
      running. Peak plantar pressures in the forefoot decreased after running. The
      pressure-time integral decreased during the heel strike phase in the internal
      edge of the foot. In addition, a decrease was found in the pressure-time integral
      during the heel-off phase in the internal and rearfoot edges. CONCLUSIONS: The
      findings suggest that after 45 min of running, a pronated foot tends to change
      into a more neutral position, and decreased plantar pressures were found after
      the run.

PMID- 27031547
TI  - Relationship Between Faculty and Standardized Patient Assessment Scores of
      Podiatric Medical Students During a Standardized Performance Assessment
      Laboratory.
AB  - BACKGROUND: Direct assessment of health professional student performance of
      clinical skills can be accurately performed in the standardized performance
      assessment laboratory (SPAL), typically by health professional faculty. However,
      owing to time and economic considerations, nonmedical individuals have been
      specially trained to perform the same function (standardized patients [SPs]).
      This study compared the assessment scores of the history and physical examination
      components of a SPAL designed for second-year podiatric medical students at Des
      Moines University (DMU) by a podiatry medical faculty member and SPs. METHODS: A
      total of 101 students from the classes of 2015 and 2016 were evaluated in 2013
      and 2014 by 11 to 13 SPs from the DMU SPAL program. The video recordings of these
      101 students were then evaluated by one faculty member from the College of
      Podiatric Medicine and Surgery at DMU. RESULTS: The Pearson correlation
      coefficient for each class showed a strong linear relationship between SP and
      faculty assessment scores. The associations between SP and faculty assessment
      scores in the history, physical examination, and combined history and physical
      examination components for the 2016 class (0.706, 0.925, and 0.911, respectively)
      were found to be stronger than those for the 2015 class (0.697, 0.791, and 0.791,
      respectively). CONCLUSIONS: This study indicated that there are strong
      associations between the assessment scores of trained SPs and faculty for the
      history, physical examination, and combined history and physical examination
      components of second-year SPAL activity for podiatric medical students.

PMID- 27031549
TI  - Initial Report on the Use of In-Office Cone Beam Computed Tomography for Early
      Diagnosis of Osteomyelitis in Diabetic Patients.
AB  - Osteomyelitis is one of the most feared sequelae of diabetic foot ulceration,
      which often leads to lower-extremity amputation and disability. Early diagnosis
      of osteomyelitis increases the likelihood of successful treatment and may limit
      the amount of bone resected, preserving ambulatory function. Although a variety
      of techniques exist for imaging the diabetic foot, standard radiography is still
      the only in-office imaging modality used today. However, radiographs lack
      sensitivity and specificity, making it difficult to diagnose bone infection at
      its early stages. In this report, we describe our initial experience with a cone
      beam computed tomography (CBCT)-based device, which may serve as an accurate and
      readily available tool for early diagnosis of osteomyelitis in a patient with
      diabetes. Two patients with infected diabetic foot ulcers were evaluated for
      osteomyelitis using radiography and CBCT. Positive imaging findings were
      confirmed by bone biopsy. In both patients, CBCT captured early osteolytic
      changes that were not apparent on radiographs, leading to early surgical
      intervention and successful treatment. The CBCT was helpful in facilitating
      detection and early clinical intervention for osteomyelitis in two diabetic
      patients with foot ulcers. These results are encouraging and warrant future
      evaluation. 

PMID- 27031548
TI  - Surgical Management of Irreducible Dislocation of the Peroneus Longus Tendon A
      Case Report.
AB  - Peroneal tendon dislocation is often overlooked because the mechanism of injury
      is similar to that of lateral ligament sprains and the frequency of the disease
      is low. Therefore, it is difficult to treat peroneal tendon dislocation when
      diagnosed in the chronic state. Furthermore, because irreducible peroneal tendon
      dislocation has multiple causes, treatment is much harder. Herein, we present a
      rare case of irreducible dislocation caused by a complex pathogenesis. Surgical
      treatment yielded good results. Orthopedic surgeons should be aware of this issue
      and consider it in the preoperative simulation. 

PMID- 27031550
TI  - DermACELL: Human Acellular Dermal Matrix Allograft A Case Report.
AB  - Diabetes often causes ulcers on the feet of diabetic patients. A 56-year-old,
      insulin-dependent, diabetic woman presented to the wound care center with a
      Wagner grade 3 ulcer of the right heel. She reported a 3-week history of
      ulceration with moderate drainage and odor and had a history of ulceration and
      osteomyelitis in the contralateral limb. Rigorous wound care, including
      hospitalization; surgical incision and drainage; intravenous antibiotic drug
      therapy; vacuum-assisted therapy; and a new room temperature, sterile, human
      acellular dermal matrix graft were used to heal the wound, save her limb, and
      restore her activities of daily living. This case presentation involves
      alternative treatment of a diabetic foot ulcer with this new acellular dermal
      matrix, DermACELL. 

PMID- 27031551
TI  - Perniosis A Case Report with Literature Review.
AB  - Perniosis, or chilblain, is an uncommon condition of the acral skin. Presented
      herein is a case report of a 65-year-old otherwise healthy construction worker
      with perniosis. He had a 3-year history of lesions on the fingers and toes
      brought on by cold, damp weather. On initial presentation, a biopsy sample was
      taken of a hallux lesion, and the patient was given a trial course of nifedipine
      therapy. Follow-up at 3 weeks showed complete relief of symptoms with nifedipine
      use, and the biopsy results confirmed the diagnosis. The etiology and
      pathogenesis of perniosis are reviewed. Differential diagnoses and treatment
      options are reviewed and discussed. Nifedipine therapy has been shown to be
      effective and should be considered the standard of care in the treatment of
      perniosis along with avoidance of cold, damp environments, with protection using
      gloves and warm socks. 

PMID- 27031552
TI  - Eccrine Syringofibroadenomatosis of the Soles.
AB  - Eccrine syringofibroadenoma is a rare adnexal tumor with acrosyringeal
      differentiation. It was first described by Mascaro in 1963. Its clinical
      presentation varies from a solitary nodule, keratotic papule, verrucous plaque,
      or palmoplantar keratoderma to multiple lesions with linear or diffuse
      distributions. Age at onset ranges from 16 to 80 years. Lesion distribution is
      wide and includes the face, back, abdomen, buttocks, extremities, and, rarely,
      nails. There are five subtypes of eccrine syringofibroadenoma. Histologically,
      eccrine syringofibroadenoma, independent of the subtype, is characterized by
      anastomosing cords of acrosyringeal cells forming ductal structures in a
      fibrovascular stroma and attached to the undersurface of the epidermis in
      multiple foci. In this article, we describe a 51-year-old woman diagnosed as
      having eccrine syringofibroadenomatosis. 

PMID- 27031553
TI  - Necrotizing Fasciitis of the Lower Extremity Caused by Serratia marcescens A Case
      Report.
AB  - Necrotizing fasciitis is a rare and potentially fatal infection, with mortality
      of up to 30%. This case report describes a patient recovering from a laryngectomy
      for laryngeal squamous cell cancer who developed nosocomial necrotizing fasciitis
      of the lower extremity due to Serratia marcescens . Only eight cases of
      necrotizing fasciitis exclusive to the lower extremity due to S marcescens have
      been previously reported. Patients with S marcescens necrotizing fasciitis of the
      lower extremity often have multiple comorbidities, are frequently
      immunosuppressed, and have a strikingly high mortality rate. 

PMID- 27031554
TI  - Diagnostic Ultrasound of the Soleal Sling.
AB  - The soleal sling may be a site of tibial nerve entrapment. Objective diagnosis of
      this syndrome is difficult with current nerve conduction study techniques,
      magnetic resonance imaging, and neurosensory testing. Diagnostic ultrasound is
      ideally suited to visualize the tibial nerve statically and dynamically as it
      enters the soleal sling, thus making an objective diagnosis of soleal sling
      impingement much easier. 

PMID- 27031555
TI  - Giant Glomus Tumor and Neuroma in the Fifth Ray A Case Report.
AB  - We present the case of a patient with a glomus tumor that was atypical because of
      its large size and histologic characteristics. It was located in the dorsal
      distal zone of the fifth ray of the left foot and was associated with a neuroma
      under the fifth metatarsal head. Although the pain (of a neurologic type) was
      attributed to the neuroma, the unknown nature and evolution of the dorsal lesion
      (glomus tumor) made surgical treatment necessary. Surgery, together with
      compensating treatment of the functional alterations of the patient's feet
      (pronation of the subastragalar joint, supination of the forefoot, and fifth
      metatarsal overload syndrome), resolved the case. 

PMID- 27031556
TI  - Diagnosis and Management of Onychomycosis Perspectives from a Joint Podiatric
      Medicine-Dermatology Roundtable.
AB  - Onychomycosis is a fungal infection, and, as such, one of the goals of treatment
      should be eradication of the infective agent. Despite this, in contrast to
      dermatologists, many podiatric physicians do not include antifungals in their
      onychomycosis treatment plans. Before initiating treatment, confirmation of
      mycologic status via laboratory testing (eg, microscopy with potassium hydroxide
      preparation, histopathology with periodic acid-Schiff staining, fungal culture,
      and polymerase chain reaction) is important; however, more podiatric physicians
      rely solely on clinical signs than do dermatologists. These dissimilarities may
      be due, in part, to differences between specialties in training, reimbursement
      patterns, or practice orientation, and to explore these differences further, a
      joint podiatric medicine-dermatology roundtable was convened. In addition,
      treatment options have been limited owing to safety concerns with available oral
      antifungals and relatively low efficacy with previously available topical
      treatments. Recently approved topical treatments-efinaconzole and tavaborole
      offer additional options for patients with mild-to-moderate disease. Debridement
      alone has no effect on mycologic status, and it is recommended that it be used in
      combination with an oral or topical antifungal. There is little to no clinical
      evidence to support the use of lasers or over-the-counter treatments for
      onychomycosis. After a patient has achieved cure (absence of clinical signs or
      absence of fungus with minimal clinical signs), lifestyle and hygiene measures,
      prophylactic/maintenance treatment, and proactive treatment for tinea pedis,
      including in family members, may help maintain this status. 

PMID- 27031561
TI  - Correction: Human observers have optimal introspective access to perceptual
      processes even for visually masked stimuli.

PMID- 27031562
TI  - CHARMM TIP3P Water Model Suppresses Peptide Folding by Solvating the Unfolded
      State.
AB  - The accuracy of molecular dynamics simulations depends on the underlying force
      field, defined by the form and parametrization of the interparticle potential
      functions and the water model. The treatment of the solvent is crucial in
      molecular dynamics force fields, as hydrophobic interactions and hydrogen bonding
      are important molecular forces. The widely used CHARMM force field was originally
      parametrized using a modified version of the TIP3P water model (mTIP3P),
      including Lennard-Jones interactions between hydrogens and oxygens. The latest
      version, CHARMM36, was optimized using the standard TIP3P water model (sTIP3P)
      for proteins, while mTIP3P is still being used for lipids. Our replica exchange
      molecular dynamics simulations on dynamic peptides show that the CHARMM36 force
      field with mTIP3P water yields less realistic folding than with sTIP3P water.
      Analysis of the dimensions and hydrogen bonding of the unfolded state reveals
      that the peptides are more solvated and extended in mTIP3P, due to a higher
      solvation energy of the peptide in this water model. We recommend using CHARMM36
      with sTIP3P when simulating peptides, folded proteins, and natively unfolded
      proteins, but combinations of proteins with lipids would require a
      reparametrization to make their water models compatible.

PMID- 27031564
TI  - Additional data on the clinical phenotype of Helsmoortel-Van der Aa syndrome
      associated with a novel truncating mutation in ADNP gene.

PMID- 27031565
TI  - Pyrazolylamine Derivatives Reveal the Conformational Switching between Type I and
      Type II Binding Modes of Anaplastic Lymphoma Kinase (ALK).
AB  - Most anaplastic lymphoma kinase (ALK) inhibitors adopt a type I binding mode, but
      only limited type II ALK structural studies are available. Herein, we present the
      structure of ALK in complex with N1-(3-4-[([5-(tert-butyl)-3
      isoxazolyl]aminocarbonyl)amino]-3-methylphenyl-1H-5-pyrazolyl)-4-[(4
      methylpiperazino)methyl]benzamide (5a), a novel ALK inhibitor adopting a type II
      binding mode. It revealed binding of 5a resulted in the conformational change and
      reposition of the activation loop, alphaC-helix, and juxtamembrane domain, which
      are all important domains for the autoinhibition mechanism and downstream signal
      pathway regulation of ALK. A structure-activity relationship study revealed that
      modifications to the structure of 5a led to significant differences in the ALK
      potency and altered the protein structure of ALK. To the best of our knowledge,
      this is the first structural biology study to directly observe how changes in the
      structure of a small molecule can regulate the switch between the type I and type
      II binding modes and induce dramatic conformational changes.

PMID- 27031566
TI  - Surface hopping investigation of benzophenone excited state dynamics.
AB  - We present a simulation of the photodynamics of benzophenone for the first 20 ps
      after n ->pi* excitation, performed by trajectory surface hopping calculations
      with on-the-fly semiempirical determination of potential energy surfaces and
      electronic wavefunctions. Both the dynamic and spin-orbit couplings are taken
      into account, and time-resolved fluorescence emission is also simulated. The
      computed decay time of the S1 state is in agreement with experimental
      observations. The direct S1-> T1 intersystem crossing (ISC) accounts for about
      2/3 of the S1 decay rate. The remaining 1/3 goes through T2 or higher triplets.
      The nonadiabatic transitions within the triplet manifold are much faster than ISC
      and keep the population of T1 at about 3/4 of the total triplet population, and
      that of the other states (mainly T2) at 1/4. Two internal coordinates are
      vibrationally active immediately after n ->pi* excitation: one is the C[double
      bond, length as m-dash]O stretching and the other one is a combination of the
      conrotatory torsion of phenyl rings and of bending involving the carbonyl C atom.
      The period of the torsion-bending mode coincides with oscillations in the time
      resolved photoelectron spectra of Spighi et al. and substantially confirms their
      assignment.

PMID- 27031563
TI  - Diabetic retinopathy: intravitreal vascular endothelial growth factor inhibitors
      for diabetic macular oedema.
AB  - INTRODUCTION: Diabetic retinopathy is the most common microvascular complication
      of diabetes. It is also the most common cause of blindness in working-age adults
      in industrialised nations. Older people and those with worse diabetes control,
      hypertension, and hyperlipidaemia are most at risk. Diabetic macular oedema,
      which can occur at any stage of diabetic retinopathy, is related to increased
      vascular permeability and breakdown of the blood retinal barrier, in part related
      to increased vascular endothelial growth factor (VEGF) levels. About 1% to 3% of
      people with diabetes suffer vision loss because of diabetic macular oedema.
      METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the
      following clinical questions: What are the effects of intravitreal VEGF
      inhibitors versus each other for diabetic macular oedema? What are the effects of
      intravitreal VEGF inhibitors plus laser therapy versus intravitreal VEGF
      inhibitors alone for diabetic macular oedema? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to September 2014 (Clinical
      Evidence overviews are updated periodically; please check our website for the
      most up-to-date version of this overview). RESULTS: At this update, searching of
      electronic databases retrieved 240 studies. After deduplication and removal of
      conference abstracts, 149 records were screened for inclusion in the overview.
      Appraisal of titles and abstracts led to the exclusion of 90 studies and the
      further review of 59 full publications. Of the 59 full articles evaluated, eight
      systematic reviews and four RCTs were added at this update. We performed a GRADE
      evaluation for four PICO combinations. CONCLUSIONS: In this systematic overview,
      we categorised the efficacy for six comparisons based on information about the
      effectiveness and safety of intravitreal VEGF inhibitors aflibercept,
      bevacizumab, and ranibizumab, and each of these intravitreal VEGF inhibitors plus
      laser therapy.

PMID- 27031567
TI  - The Feedback-related Negativity Codes Components of Abstract Inference during
      Reward-based Decision-making.
AB  - Behavioral control is influenced not only by learning from the choices made and
      the rewards obtained but also by "what might have happened," that is, inference
      about unchosen options and their fictive outcomes. Substantial progress has been
      made in understanding the neural signatures of direct learning from choices that
      are actually made and their associated rewards via reward prediction errors
      (RPEs). However, electrophysiological correlates of abstract inference in
      decision-making are less clear. One seminal theory suggests that the so-called
      feedback-related negativity (FRN), an ERP peaking 200-300 msec after a feedback
      stimulus at frontocentral sites of the scalp, codes RPEs. Hitherto, the FRN has
      been predominantly related to a so-called "model-free" RPE: The difference
      between the observed outcome and what had been expected. Here, by means of
      computational modeling of choice behavior, we show that individuals employ
      abstract, "double-update" inference on the task structure by concurrently
      tracking values of chosen stimuli (associated with observed outcomes) and
      unchosen stimuli (linked to fictive outcomes). In a parametric analysis, model
      free RPEs as well as their modification because of abstract inference were
      regressed against single-trial FRN amplitudes. We demonstrate that components
      related to abstract inference uniquely explain variance in the FRN beyond model
      free RPEs. These findings advance our understanding of the FRN and its role in
      behavioral adaptation. This might further the investigation of disturbed abstract
      inference, as proposed, for example, for psychiatric disorders, and its
      underlying neural correlates. 

PMID- 27031568
TI  - The effect of oxytocin on osseointegration of titanium implant in ovariectomized
      rats.
AB  - INTRODUCTION: Oxytocin (OT) was reported to control differentiation of human
      mesenchymal stem cells and reverse osteoporosis (OP). This study investigated the
      effect of systematical treatment of OT on implant osseointegration in
      ovariectomized (OVX) rats. MATERIAL AND METHODS: Twenty female rats received
      bilateral ovariectomy. Twelve weeks later, all animals were randomly assigned to
      control or experimental group. Each rat received two implants at the distal
      femoral metaphysis. From the first postoperative day, rats in experiment group
      received subcutaneous injection of OT (1 mg/kg . d), while animals in control
      group received vehicle. Twelve weeks after implantation, specimens containing
      implants were harvested and evaluated by histology, micro-CT, and push-out test.
      Tibiae were also harvested to evaluate the effect of OT on intact bone tissue of
      OVX rats. RESULTS: Compared with control, OT treatment increased the relative
      bone volume surrounding the implant by 2.2 times, the percent implant
      osseointegration by 0.62 times, and the maximum push-out force by 2.25 times.
      Increased bone mass was also observed in histological sections of distal femur
      with implant and intact bone tissue of the proximal tibiae. CONCLUSION: Systemic
      administration of OT promoted peri-implant bone healing and osseointegration of
      titanium implant and recovered the negative effects of OP in undisturbed bone
      tissue partially.

PMID- 27031569
TI  - Level of Evidence Descriptions With Examples.
AB  - The level of evidence (LOE) method provides journal readers with a quick
      appraisal of study quality. The most widely recognized LOE assessment tool is
      that from the Oxford Centre for Evidence-Based Medicine, and these guidelines are
      often adapted for other purposes. The assigned LOE typically depends on the
      design and quality of the study as well as the impact of the results. Because of
      the differing methods for classifying LOE, the author or journal reader should
      fully understand the criteria before assimilating data. 

PMID- 27031570
TI  - Exposure to widespread environmental endocrine disrupting chemicals and human
      sperm sex ratio.
AB  - In recent years, a trend toward a declining proportion of male births has been
      noted in several, but not all, industrialized countries. The underlying reason
      for the drop in the sex ratio is unclear, but one theory states that widespread
      environmental endocrine disrupting chemicals affecting the male reproductive
      system in a negative manner could be part of the explanation. The present study
      was designed to investigate whether the urinary phthalate, pyrethroids and
      polycyclic aromatic hydrocarbons metabolites concentrations were associated with
      sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of
      age who attended infertility clinic in Lodz, Poland for diagnostic purposes with
      normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen
      concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by
      fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were
      measured by high performance liquid chromatography, phthalate metabolites were
      analyzed using a procedure based on the LC-MS/MS methods and metabolites of
      synthetic pyrethroids were assessed by gas chromatography ion-tap mass
      spectrometry method. After adjustment for potential confounders (past diseases,
      age, abstinence, smoking, alcohol consumption, sperm concentration, motility,
      morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X
      sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively). As this is
      the first study to elucidate the association between the level of metabolites of
      widespread environmental endocrine disrupting chemicals (phthalates, synthetic
      pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm
      therefore, these findings require further replication in other populations. 

PMID- 27031571
TI  - Dynamics and recovery of a sediment-exposed Chironomus riparius population: A
      modelling approach.
AB  - Models can be used to assess long-term risks of sediment-bound contaminants at
      the population level. However, these models usually lack the coupling between
      chemical fate in the sediment, toxicokinetic-toxicodynamic processes in
      individuals and propagation of individual-level effects to the population. We
      developed a population model that includes all these processes, and used it to
      assess the importance of chemical uptake routes on a Chironomus riparius
      population after pulsed exposure to the pesticide chlorpyrifos. We show that
      particle ingestion is an important additional exposure pathway affecting C.
      riparius population dynamics and recovery. Models ignoring particle ingestion
      underestimate the impact and the required recovery times, which implies that they
      underestimate risks of sediment-bound chemicals. Additional scenario studies
      showed the importance of selecting the biologically relevant sediment layer and
      showed population effects in the long term. 

PMID- 27031572
TI  - Agency Problems and Airport Security: Quantitative and Qualitative Evidence on
      the Impact of Security Training.
AB  - We analyze the issue of agency costs in aviation security by combining results
      from a quantitative economic model with a qualitative study based on semi
      structured interviews. Our model extends previous principal-agent models by
      combining the traditional fixed and varying monetary responses to physical and
      cognitive effort with nonmonetary welfare and potentially transferable value of
      employees' own human capital. To provide empirical evidence for the tradeoffs
      identified in the quantitative model, we have undertaken an extensive interview
      process with regulators, airport managers, security personnel, and those tasked
      with training security personnel from an airport operating in a relatively high
      risk state, Turkey. Our results indicate that the effectiveness of additional
      training depends on the mix of "transferable skills" and "emotional" buy-in of
      the security agents. Principals need to identify on which side of a critical
      tipping point their agents are to ensure that additional training, with attached
      expectations of the burden of work, aligns the incentives of employees with the
      principals' own objectives.

PMID- 27031573
TI  - Selective modification of nanoparticle arrays by laser-induced self assembly
      (MONA-LISA): putting control into bottom-up plasmonic nanostructuring.
AB  - Nano-structuring of metals is one of the greatest challenges for the future of
      plasmonic and photonic devices. Such a technological challenge calls for the
      development of ultra-fast, high-throughput and low-cost fabrication techniques.
      Laser processing, accounts for the aforementioned properties, representing an
      unrivalled tool towards the anticipated arrival of modules based in metallic
      nanostructures, with an extra advantage: the ease of scalability. In the present
      work we take advantage of the ability to tune the laser wavelength to either
      match the absorption spectral profile of the metal or to be resonant with the
      plasma oscillation frequency, and demonstrate the utilization of different
      optical absorption mechanisms that are size-selective and enable the fabrication
      of pre-determined patterns of metal nanostructures. Thus, we overcome the
      greatest challenge of Laser Induced Self Assembly by combining simultaneously
      large-scale character with atomic-scale precision. The proposed process can serve
      as a platform that will stimulate further progress towards the engineering of
      plasmonic devices. 

PMID- 27031574
TI  - Comparison of screening questionnaires to identify psoriatic arthritis in a
      primary-care population: a cross-sectional study.
AB  - BACKGROUND: Many questionnaires are available for assessment of psoriatic
      arthritis (PsA), but there is little evidence comparing them. OBJECTIVES: To test
      the proposed CONTEST questionnaire, which was developed to identify patients with
      psoriasis who have undiagnosed PsA, and compare it with the validated Psoriasis
      Epidemiology Screening Tool (PEST) questionnaire in a primary-care setting.
      METHODS: A random sample of adult patients with psoriasis and no diagnosis of
      arthritis was identified from five general practice surgeries in Yorkshire, U.K.
      Consenting patients completed both questionnaires and were assessed by a
      dermatologist and rheumatologist. Diagnosis of PsA was made by the assessing
      rheumatologist. Receiver operator characteristic (ROC) curve analysis examined
      the sensitivity and specificity of potential cut points. RESULTS: In total 932
      packs were sent to recruit 191 (20.5%) participants. Of these, 169 (88.5%) were
      confirmed to have current or previous psoriasis. Using physician diagnosis 17
      (10.1%) were found to have previously undiagnosed PsA, while 90 (53.3%) had
      another musculoskeletal complaint and 62 (36.7%) had no musculoskeletal problems.
      Using ROC curve analysis, all of the questionnaires showed a significant ability
      to identify PsA. The area under the curve (AUC) for the CONTEST questionnaires
      was slightly higher than that of PEST (0.69 and 0.70 vs. 0.65), but there was no
      significant difference identified. Examining the sensitivities and specificities
      for the different cut points suggested that a PEST score >= 2 would perform
      better in this dataset, and the optimal scores for CONTEST and CONTEST plus joint
      manikin were 3 and 4, respectively. CONCLUSIONS: The accuracy of the
      questionnaires to identify PsA appeared similar, with a slightly higher AUC for
      the CONTEST questionnaires. The optimal cut points in this study appeared lower
      than in previous studies.

PMID- 27031575
TI  - Identification of the constituents and metabolites in rat plasma after oral
      administration of HuanglianShangqing pills by ultra high-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry.
AB  - An ultra high-performance liquid chromatography/quadrupole time-of-flight mass
      spectrometry method was established to detect and identify the chemical
      constituents and metabolites of HuanglianShangqing pill (HLSQ) in vitro and in
      vivo. A total of 96 compounds were characterized in HLSQ extracts. In vivo, 45
      prototype components and 53 metabolites of HLSQ were detected in rat plasma and
      tentatively identified, three of which are new. The novel metabolic pathways of
      rhein and hesperetin were revealed. The bioactive compounds of HLSQ undergo phase
      I metabolic routes of hydrogenation, hydroxylation, hydrolysis, demethylation and
      phase II metabolic routes of glucuronide, sulfation, acetylation and methylation.
      Among these, glucuronide conjugation is the main metabolic pathway of the active
      compounds of HLSQ in rat plasma. 

PMID- 27031576
TI  - Fingerprinting of traditional Chinese medicines on the C18-Diol mixed-mode column
      in online or offline two-dimensional liquid chromatography on the single column
      modes.
AB  - In the present study, a mixed-mode stationary phase, C18-Diol, was applied for
      fingerprint analysis of traditional Chinese medicines. Hydrophobic, hydrogen
      bonding and electrostatic interactions were demonstrated to contribute the
      retention separately or jointly, which endowed the C18-Diol stationary phase with
      distinct selectivity compared to the bare C18 one. The separation of total
      alkaloids extracted from Fritillaria hupehensis was compared on the C18-Diol and
      conventional C18 column with the greater resolving power and better symmetry
      responses on the former one. Besides, a novel two-dimensional liquid
      chromatography on the single column (2D-LC-1C) was realized on C18-Diol with the
      offline mode for the alcohol extract of Fritillaria hupehensis and online mode
      for Ligusticum chuanxiong Hort. The early co-eluted extracted components with
      great polarity on the first dimension were reinjected on the same column and well
      separated on the second dimension. The results exhibited that the two
      complementary RPLC and HILIC modes on C18-Diol stationary phase enhanced the
      separation capacity and revealed more abundant chemical information of the
      sample, which was a powerful tool in analyzing complex herbal medicines. 

PMID- 27031577
TI  - Force field development and simulations of senior dialkyl sulfoxides.
AB  - Thermodynamics, structure, and dynamics of diethyl sulfoxide (DESO) and ethyl
      methyl sulfoxide (EMSO) were investigated using ab initio calculations and non
      polarizable potential based molecular dynamics (MD) simulations. The additive
      pairwise force field (FF) for EMSO and DESO was proposed for the first time,
      preserving explicit compatibility with their most known homologue, DMSO. The
      simulations reveal similar structures and thermodynamic properties of DMSO, DESO
      and EMSO. However, the transport properties are significantly different: DESO and
      DMSO are less mobile and an order of magnitude more viscous. Furthermore, dipole
      reorientation in DESO and EMSO occurs ca. 2-4 times slower than in DMSO at room
      temperature. This observation favors applications of higher sulfoxides as
      cryoprotectants and provides a microscopic interpretation of the earlier
      experimental data. 

PMID- 27031579
TI  - Metabolic abnormalities induced by mitochondrial dysfunction in skeletal muscle
      of the renal carcinoma Eker (TSC2+/-) rat model.
AB  - Tuberous sclerosis complex 2 (TSC2) is a mediator of insulin signal transduction,
      and a loss of function in TSC2 induces hyperactivation of mTORC1 pathway, which
      leads to tumorigenesis. We have previously demonstrated that Eker rat model,
      which is heterozygous for a TSC2 mutation, exhibits hyperglycemia and
      hyperketonemia. The present study was to investigate whether these changes also
      can affect metabolism in skeletal muscle of the Eker rat. Wild-type (TSC2+/+) and
      Eker (TSC2+/-) rats underwent an oral glucose tolerance test, and the latter
      showed decrease in whole-body glucose utilization. Additionally, reductions in
      the expression of glycolysis-, lipolysis-, and ketone body-related genes in
      skeletal muscle were observed in Eker rats. Furthermore, ATP content and
      mitochondrial DNA copy number were lower in skeletal muscle of Eker rats. These
      data demonstrate that heterozygous to mutation TSC2 not only affects the liver
      metabolism, but also skeletal muscle metabolism, via mitochondrial dysfunction. 

PMID- 27031580
TI  - Origin and Tunability of Unusually Large Surface Capacitance in Doped Cerium
      Oxide Studied by Ambient-Pressure X-Ray Photoelectron Spectroscopy.
AB  - The volumetric redox (chemical) capacitance of the surface of CeO2-delta films is
      quantified in situ to be 100-fold larger than the bulk values under catalytically
      relevant conditions. Sm addition slightly lowers the surface oxygen
      nonstoichiometry, but effects a 10-fold enhancement in surface chemical
      capacitance by mitigating defect interactions, highlighting the importance of
      differential nonstoichiometry for catalysis. 

PMID- 27031578
TI  - Associations of cortisol/testosterone and cortisol/sex hormone-binding globulin
      ratios with atherosclerosis in middle-age women.
AB  - BACKGROUND AND AIMS: The cortisol/testosterone (C/T) ratio has been hypothesized
      to be a better predictor of atherosclerosis than cortisol alone. No study has
      assessed whether the C/T and C/sex hormone-binding globulin (SHBG) ratios are
      associated with atherosclerosis in a U.S. population sample. METHODS: This
      substudy included 367 women who had both cortisol from year 15 and testosterone
      and SHBG at year 16 of the Coronary Artery Risk Development in Young Adults
      study, an ongoing observational cohort in the United States. Of these, intima
      media thickness (IMT) was available at follow-up year 20 in 339 (n = 332 with
      measurement at carotid bulb), and 303 were free of prevalent coronary artery
      calcium (CAC) at year 15. Area under the curve (AUC) of salivary cortisol was
      available in 302 individuals. Ratios of AUCs of cortisol to total testosterone,
      free testosterone, and SHBG were categorized into tertiles. Associations with CAC
      and IMT were assessed by regression models adjusted for age, race, body mass
      index, systolic blood pressure, menopause, oral contraceptive use, diabetes,
      alcohol, and smoking. RESULTS: Only the highest tertile of the AUC/free
      testosterone ratio was positively associated with carotid bulb IMT (beta = 0.088,
      P = 0.006). This tertile was also positively associated with new onset CAC
      between year 15 and 25 (OR 3.45, 95% CI 1.18-10.06). Tertiles of cortisol or
      testosterone alone were not associated with new onset CAC. CONCLUSION: AUC/Free
      testosterone ratio may be more associated with atherosclerosis in women than
      either indicator alone. The ratio may serve as a suitable biomarker of cortisol
      linked stress.

PMID- 27031582
TI  - The mitral annular displacement by two-dimensional speckle tracking: a new tool
      in evaluating the left atrial function.
AB  - BACKGROUND: The methods used to characterize the volume change and the
      deformation of the left atrium are highly dependent on technical factors and
      difficult to use in a clinical environment. The aim of this study was to
      demonstrate that mitral annular displacement by speckle tracking can be an
      alternative method to studying the longitudinal left atrial function. METHODS:
      Ninety study participants (54% men), with a mean age of 53(+/-15) years,
      underwent a complete echocardiographic examination, comprising two-dimensional,
      three-dimensional and tissue Doppler imaging (TDI). They were divided into normal
      individuals (35) and patients having an abnormal echocardiography (55). RESULTS:
      There was a very strong correlation between three-dimensional volumetric function
      and mitral annular displacement, both for the reservoir (r = 0.78; P < 0.0001)
      and contractile (r = 0.76; P < 0.0001) functions. The correlation with the
      longitudinal strain displayed an r = 0.87, P > 0.0001 for the reservoir and r =
      0.81, P < 0.0001 for the contractile function. The systolic speed in pulsed TDI
      and the systolic displacement had an r = 0.83, P < 0.0001. Mitral annular
      displacement was a very good discriminator for normal versus abnormal
      participants [area under the curve (AUC) for reservoir = 0.872 and for
      contractile = 0.843; P < 0.0001], performing less well than three-dimensional
      (AUC reservoir = 0.892 and contractile = 0.915; P < 0.0001) or deformation (AUC =
      0.921 and 0.903 respectively; P < 0.0001), but better than pulsed TDI (AUC =
      0.807; P < 0.0001). The percentage error was +/-15% for interobserver and +/-12%
      for intraobserver variability. The time taken for displacement analysis was 9 +/-
      3 s for an experienced cardiologist and 12 +/- 4 s for a beginner. CONCLUSION:
      Mitral annular displacement by speckle tracking is a reliable and fast method to
      evaluate left atrial function. Given the strength of the correlations with strain
      parameters, it could be used as a surrogate measure of the deformation of left
      atrium.

PMID- 27031581
TI  - Capture and characterization of influenza A virus from primary samples using
      glycan bead arrays.
AB  - Influenza A viruses (IAVs) utilize sialylated host glycans as ligands for binding
      and infection. The glycan-binding preference of IAV hemagglutinin (HA) is an
      important determinant of host specificity. Propagation of IAV in embryonated
      chicken eggs and cultured mammalian cells yields viruses with amino acid
      substitutions in the HA that can alter the binding specificity. Therefore, it is
      important to determine the binding specificity of IAV directly in primary samples
      since it reflects the actual tropism of virus in nature. We developed a novel
      platform for analysis of IAV binding specificity in samples that contain very low
      virus titers. This platform consists of a high-density flexible glycan display on
      magnetic beads, which promotes multivalent interactions with the viral HA. Glycan
      bound virus is detected by quantifying the viral neuraminidase activity via a
      fluorogenic reporter, 2'-(4-methylumbelliferyl)-alpha-d-N-acetylneuraminic acid.
      This method eliminates the need for labeling the virus and significantly enhances
      the sensitivity of detection.

PMID- 27031584
TI  - Steroid receptors in human ejaculated sperm as molecular markers of the
      detrimental effects related to the pathophysiology of testicular varicocele.
AB  - The exact physiopathologic effect of testicular varicocele on male fertility is
      not defined yet. The detrimental role of the varicocele in fertility is supported
      by the presence of a higher frequency of affected men among the infertile
      population. However, the mechanism/s by which a varicocele impairs sperm
      production, structure and function, is not known. In spite of active interest,
      our understanding of the human male gamete ultrastructural molecular organisation
      is still incomplete and therefore our knowledge of the sperm molecular anatomy is
      very limited. The presence of steroid binding sites on human spermatozoa has been
      evidenced since the 1970s, and afterwards, spermatozoa physiology was linked to
      the action of different steroids. The presence of steroid/steroid receptor
      systems was demonstrated in mature spermatozoa as membrane but also as nuclear
      conventional receptors, suggesting that both systemic and local steroids, through
      sperm receptors, may influence male fertility. From new data, it emerges that
      varicocele may induce damage in the male gamete at molecular level, opening a new
      chapter in the already multifactorial pathophysiology of the varicocele,
      complicating this issue. In sperm from varicocele, a decreased expression of
      steroid receptors and a consequent reduced responsiveness to steroids may
      represent a mechanism involved in the physiopathology of varicocele. Therefore,
      the modulation of these nuclear receptors pave the way for novel therapeutic
      opportunities in the treatment of the male pathologies related to human
      reproduction. The purpose of this review is to gain new insight into the
      physiopathology of varicocele and to study its impact on human sperm molecular
      anatomy. 

PMID- 27031585
TI  - Campylobacter jejuni Infections Associated with Raw Milk Consumption--Utah, 2014.
AB  - In May 2014, the Utah Public Health Laboratory (UPHL) notified the Utah
      Department of Health (UDOH) of specimens from three patients infected with
      Campylobacter jejuni yielding indistinguishable pulsed-field gel electrophoresis
      (PFGE) patterns. All three patients had consumed raw (unpasteurized and
      nonhomogenized) milk from dairy A. In Utah, raw milk sales are legal from farm to
      consumer with a sales permit from the Utah Department of Agriculture and Food
      (UDAF). Raw milk dairies are required to submit monthly milk samples to UDAF for
      somatic cell and coliform counts, both of which are indicators of raw milk
      contamination. Before this cluster's identification, dairy A's routine test
      results were within acceptable levels (<400,000 somatic cells/mL and <10 coliform
      colony forming units/mL). Subsequent enhanced testing procedures recovered C.
      jejuni, a fastidious organism, in dairy A raw milk; the isolate matched the
      cluster pattern. UDAF suspended dairy A's raw milk permit during August 4-October
      1, and reinstated the permit when follow-up cultures were negative. Additional
      cases of C. jejuni infection were identified in October, and UDAF permanently
      revoked dairy A's permit to sell raw milk on December 1. During May 9-November 6,
      2014, a total of 99 cases of C. jejuni infection were identified. Routine somatic
      cell and coliform counts of raw milk do not ensure its safety. Consumers should
      be educated that raw milk might be unsafe even if it meets routine testing
      standards. 

PMID- 27031587
TI  - Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8
      Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United
      States, 2012.
AB  - PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2012.
      DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring
      (ADDM) Network is an active surveillance system that provides estimates of the
      prevalence and characteristics of ASD among children aged 8 years whose parents
      or guardians reside in 11 ADDM Network sites in the United States (Arkansas,
      Arizona, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, South
      Carolina, Utah, and Wisconsin). Surveillance to determine ASD case status is
      conducted in two phases. The first phase consists of screening and abstracting
      comprehensive evaluations performed by professional service providers in the
      community. Data sources identified for record review are categorized as either 1)
      education source type, including developmental evaluations to determine
      eligibility for special education services or 2) health care source type,
      including diagnostic and developmental evaluations. The second phase involves the
      review of all abstracted evaluations by trained clinicians to determine ASD
      surveillance case status. A child meets the surveillance case definition for ASD
      if one or more comprehensive evaluations of that child completed by a qualified
      professional describes behaviors that are consistent with the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnostic
      criteria for any of the following conditions: autistic disorder, pervasive
      developmental disorder-not otherwise specified (including atypical autism), or
      Asperger disorder. This report provides ASD prevalence estimates for children
      aged 8 years living in catchment areas of the ADDM Network sites in 2012, overall
      and stratified by sex, race/ethnicity, and the type of source records (education
      and health records versus health records only). In addition, this report
      describes the proportion of children with ASD with a score consistent with
      intellectual disability on a standardized intellectual ability test, the age at
      which the earliest known comprehensive evaluation was performed, the proportion
      of children with a previous ASD diagnosis, the specific type of ASD diagnosis,
      and any special education eligibility classification. RESULTS: For 2012, the
      combined estimated prevalence of ASD among the 11 ADDM Network sites was 14.6 per
      1,000 (one in 68) children aged 8 years. Estimated prevalence was significantly
      higher among boys aged 8 years (23.6 per 1,000) than among girls aged 8 years
      (5.3 per 1,000). Estimated ASD prevalence was significantly higher among non
      Hispanic white children aged 8 years (15.5 per 1,000) compared with non-Hispanic
      black children (13.2 per 1,000), and Hispanic (10.1 per 1,000) children aged 8
      years. Estimated prevalence varied widely among the 11 ADDM Network sites,
      ranging from 8.2 per 1,000 children aged 8 years (in the area of the Maryland
      site where only health care records were reviewed) to 24.6 per 1,000 children
      aged 8 years (in New Jersey, where both education and health care records were
      reviewed). Estimated prevalence was higher in surveillance sites where education
      records and health records were reviewed compared with sites where health records
      only were reviewed (17.1 per 1,000 and 10.7 per 1,000 children aged 8 years,
      respectively; p<0.05). Among children identified with ASD by the ADDM Network,
      82% had a previous ASD diagnosis or educational classification; this did not vary
      by sex or between non-Hispanic white and non-Hispanic black children. A lower
      percentage of Hispanic children (78%) had a previous ASD diagnosis or
      classification compared with non-Hispanic white children (82%) and with non
      Hispanic black children (84%). The median age at earliest known comprehensive
      evaluation was 40 months, and 43% of children had received an earliest known
      comprehensive evaluation by age 36 months. The percentage of children with an
      earliest known comprehensive evaluation by age 36 months was similar for boys and
      girls, but was higher for non-Hispanic white children (45%) compared with non
      Hispanic black children (40%) and Hispanic children (39%). INTERPRETATION:
      Overall estimated ASD prevalence was 14.6 per 1,000 children aged 8 years in the
      ADDM Network sites in 2012. The higher estimated prevalence among sites that
      reviewed both education and health records suggests the role of special education
      systems in providing comprehensive evaluations and services to children with
      developmental disabilities. Disparities by race/ethnicity in estimated ASD
      prevalence, particularly for Hispanic children, as well as disparities in the age
      of earliest comprehensive evaluation and presence of a previous ASD diagnosis or
      classification, suggest that access to treatment and services might be lacking or
      delayed for some children. PUBLIC HEALTH ACTION: The ADDM Network will continue
      to monitor the prevalence and characteristics of ASD among children aged 8 years
      living in selected sites across the United States. Recommendations from the ADDM
      Network include enhancing strategies to 1) lower the age of first evaluation of
      ASD by community providers in accordance with the Healthy People 2020 goal that
      children with ASD are evaluated by age 36 months and begin receiving community
      based support and services by age 48 months; 2) reduce disparities by
      race/ethnicity in identified ASD prevalence, the age of first comprehensive
      evaluation, and presence of a previous ASD diagnosis or classification; and 3)
      assess the effect on ASD prevalence of the revised ASD diagnostic criteria
      published in the Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition.

PMID- 27031588
TI  - Managing Minor Ailments; The Public's Preferences for Attributes of Community
      Pharmacies. A Discrete Choice Experiment.
AB  - BACKGROUND: Demand for health services continues to rise. Greater use of
      community pharmacy services instead of medical services for minor ailments could
      help relieve pressure on healthcare providers in high-cost settings. Community
      pharmacies are recognised sources of treatment and advice for people wishing to
      manage these ailments. However, increasing the public's use of pharmacy services
      may depend on attributes of pharmacies and their staff. This study aimed to
      determine the general public's relative preferences for community pharmacy
      attributes using a discrete choice experiment (DCE). METHOD: A UK-wide DCE survey
      of the general public was conducted using face-to-face computer-assisted personal
      interviews. Attributes and levels for the DCE were informed by a literature
      review and a cohort study of community pharmacy customers. The context for the
      experiment was a minor ailment scenario describing flu-like symptoms. The DCE
      choice sets described two hypothetical community pharmacy services; respondents
      were asked to choose which (if either) of the two pharmacies they would prefer to
      help them manage symptoms. Data from 1,049 interviews were analysed using an
      error components logit model. Willingness to pay (WTP), a monetary measure of
      benefit, was estimated for the different attribute levels. RESULTS: When seeking
      help or treatment for flu-like symptoms, respondents most valued a pharmacy
      service that would improve their understanding and management of symptoms (WTP =
      L6.28), provided by staff who are trained (WTP (pharmacist) = L2.63: WTP(trained
      assistant) = L3.22), friendly and approachable (WTP = L3.38). Waiting time,
      pharmacy location and availability of parking also contributed to respondents'
      preferences. WTP for a service comprising the best possible combination of
      attributes and levels was calculated as L55.43. CONCLUSION: Attributes of a
      community pharmacy and its staff may influence people's decisions about which
      pharmacy they would visit to access treatment and advice for minor ailments. In
      line with the public's preferences, offering community pharmacy services that
      help people to better understand and manage symptoms, are provided promptly by
      trained staff who are friendly and approachable, and in a local setting with easy
      access to parking, has the potential to increase uptake amongst those seeking
      help to manage minor ailments. In this way it may be possible to shift demand
      away from high-cost health services and make more efficient use of scarce public
      resources.

PMID- 27031589
TI  - Long-Term Outcome Data in Patients following One Year's Use of a Fully
      Implantable Active Middle Ear Implant.
AB  - This study examined the safety and efficacy of a fully implantable active middle
      ear (AMEI) system. Outcome measures assessed AMEI performance compared with an
      optimally fitted conventional hearing aid (CHA). Fifty adults with stable,
      symmetric moderate-to-severe sensorineural hearing loss were implanted at 9
      ambulatory settings. Consonant-Nucleus-Consonant (CNC) words, Bamford-Kowel-Bench
      Speech in Noise test (BKB-SIN), Abbreviated Profile of Hearing Aid Benefit
      (APHAB), and unaided hearing thresholds in the implanted ear were compared to
      baseline measures obtained using a personal CHA. Changes in thresholds were
      observed from pre- to 12-month postoperative assessments. CNC word scores
      decreased (within 10%), and the BKB-SIN showed no change from pre- to 12-month
      postoperative time points. The APHAB revealed improvement. Findings suggest no
      difference in performance between an appropriately fit CHA and the AMEI at 12
      months. This study indicates AMEIs have the potential to help individuals who
      choose not to use CHAs. 

PMID- 27031590
TI  - Design of Poly(L-lactide)-Poly(ethylene glycol) Copolymer with Light-Induced
      Shape-Memory Effect Triggered by Pendant Anthracene Groups.
AB  - A novel light-induced shape-memory material based on poly(l-lactide)
      poly(ethylene glycol) copolymer is developed successfully by dangling the
      photoresponsive anthracene group on the PEG soft segment selectively. For
      synthesis strategy, the preprepared photoresponsive monomer N,N-bis(2
      hydroxyethyl)-9-anthracene-methanamine (BHEAA) is first embedded into PEG chains;
      then, we couple this anthracene-functionalized PEG precursor with PLA precursor
      to result in PLA-PEG-A copolymer. The composition of target product can be well
      defined by simply adjusting the feed ratio. The chemical structures of
      intermediate and final products are confirmed by (1)H NMR. Differential scanning
      calorimetry analysis of material reveals that the PEG soft segment became
      noncrystallizable when 4% or more BHEAA is introduced, and this feature is
      beneficial to the mobility of anthracene groups in polymer matrix. The static
      tensile tests show that the samples exhibit rubberlike mechanical properties
      except for the PLA-dominant one. The reversibility of [4 + 4] cycloaddition
      reaction between pendant anthracene groups in PLA-PEG-A film is demonstrated by
      UV-vis. Eventually, the light-induced shape-memory effect (LSME) is successfully
      realized in PLA-PEG-A. The results of cyclic photomechanical tests also reveal
      that the content of PLA hard segment as well as photosensitive anthracene
      moieties plays a crucial role in LSME. 

PMID- 27031591
TI  - Adrenocorticotropic hormone in serial cerebrospinal fluid in man - Subject to
      acute regulation by the hypothalamic-pituitary-adrenocortical system?
AB  - Acute regulation of adrenocorticotropic hormone (ACTH) in cerebrospinal fluid
      (CSF) by the hypothalamic-pituitary-adrenocortical system has not been
      investigated in man. In a pilot study in healthy male volunteers we measured ACTH
      every twenty minutes in serial CSF for three hours after an intravenous placebo,
      hydrocortisone (100mg) or insulin (2mg/kg) injection. No acute inhibitory or
      stimulatory effects of these interventions were discovered. Our results
      corroborate previous findings in rhesus monkeys. The regulation of CSF ACTH and
      its potential relevance for behavioral alterations in health and disease (e.g.
      major depression or anorexia nervosa) in humans need further study.

PMID- 27031592
TI  - Psychometric properties of the symptom check-list-90-R in prison inmates.
AB  - The aim of this study was to investigate the reliability, construct and criterion
      validity of the Symptom Check-List-90-R (SCL-90-R) for prison inmates. A sample
      of 427 adult prisoners was assessed at admission to the penal justice system in
      the metropolitan region of Santiago de Chile using the SCL-90-R and the mini
      international neuropsychiatric interview. We tested internal consistency using
      Cronbach's alpha. We examined construct validity using Principial Components
      Analysis and Confirmatory Factor Analysis (PCA and CFA) as well as Mokken Scale
      Analysis. Receiver Operating Characteristic (ROC) analysis was conducted to
      examine external criterion validity against diagnoses established using
      structured clinical interviews. The SCL-90-R showed good internal consistency for
      all subscales (alpha=0.76-0.89) and excellent consistency for the global scale
      (alpha=0.97). PCA yielded a 1-factor structure, which accounted for 70.7% of the
      total variance. CFA and MSA confirmed the unidimensional structure. ROC analysis
      indicated useful accuracy of the SCL-90-R to screen for severe mental disorders.
      Optimal cut-off on the Global Severity Index between severe mental disorders and
      not having any severe mental disorder was 1.42. In conclusion, the SCL-90-R is a
      reliable and valid instrument, which may be useful to screen for severe mental
      disorders at admission to the prison system.

PMID- 27031593
TI  - Gambling behaviors and psychopathology related to Attention-Deficit/Hyperactivity
      Disorder (ADHD) in problem and non-problem adult gamblers.
AB  - Previous studies showed that Pathological Gambling and Attention
      Deficit/Hyperactivity Disorder (ADHD) often co-occur. The aim of this study was
      to examine whether ADHD is associated with specific severity patterns in terms of
      gambling behavior, psychopathology and personality traits. 599 problem and non
      problem-gamblers were recruited in addiction clinics and gambling places in
      France. Subjects were assessed with the Wender-Utah Rating Scale-Child, the Adult
      ADHD Self-Report Scale, the Mini International Neuropsychiatric Interview, the
      Temperament and Character Inventory, the South Oaks Gambling Screen and
      questionnaires assessing gambling related cognitive distortions and gambling
      habits. 20.7% (n=124) of gamblers were screened positive for lifetime or current
      ADHD. Results from the multivariate analysis showed that ADHD was associated with
      a higher severity of gambling-related problems and with more psychiatric
      comorbidity. Among problem gamblers, subjects with history of ADHD were also at
      higher risk for unemployment, psychiatric comorbidity and specific dysfunctional
      personality traits. This study supports the link between gambling related
      problems and ADHD in a large sample of problem and non-problem gamblers,
      including problem-gamblers not seeking treatment. This points out the necessity
      to consider this disorder in the prevention and in the treatment of pathological
      gambling.

PMID- 27031594
TI  - Protective factors in Chinese university students at clinical high risk for
      psychosis.
AB  - The role of protective factors in symptom formation and prognosis in
      schizophrenia has been shown in many studies, but research in the early phases of
      psychosis is limited, particularly among the nonclinical subjects. Protective
      factors associated with the severity of symptoms and clinical outcomes might be
      meaningful to the establishment of prevention systems and to the development of
      optimal psychosocial interventions prior to the onset of psychosis. The present
      study compares self-reported levels of self-esteem, social support and resilience
      of 32 university students at clinical high risk for psychosis (CHR) and 32
      healthy controls in a longitudinal study design. Associations between protective
      factors with symptoms of psychosis were assessed in the CHR group. Individuals at
      CHR showed significantly lower self-esteem, social support and resilience
      compared to healthy controls. In the CHR group, lower social support and lower
      self-esteem were associated with more severe positive, negative and depressive
      symptoms. Multiple regression analyses revealed that self-esteem was the only
      significant determinant for negative, depressive symptoms and global functioning.
      In addition, we found that subjects who were fully recovered at a 6-month follow
      up survey were greater resilient and showed lower depressive symptoms at
      baseline. The result implied that resilience intervention could be effective on
      early prevention of the onset of psychosis. Moreover, implications and
      limitations of this study will be discussed.

PMID- 27031595
TI  - Adaptation and initial validation of the Patient Health Questionnaire - 9 (PHQ-9)
      and the Generalized Anxiety Disorder - 7 Questionnaire (GAD-7) in an Arabic
      speaking Lebanese psychiatric outpatient sample.
AB  - The Patient Health Questionnaire - 9 (PHQ-9) and Generalized Anxiety Disorder - 7
      (GAD-7) are short screening measures used in medical and community settings to
      assess depression and anxiety severity. The aim of this study is to translate the
      screening tools into Arabic and evaluate their psychometric properties in an
      Arabic-speaking Lebanese psychiatric outpatient sample. The patients completed
      the questionnaires, among others, prior to being evaluated by a clinical
      psychiatrist or psychologist. The scales' internal consistency and factor
      structure were measured and convergent and discriminant validity were established
      by comparing the scores with clinical diagnoses and the Psychiatric Diagnostic
      Screening Questionnaire - MDD subset (PDSQ - MDD). Results showed that the PHQ-9
      and GAD-7 are reliable screening tools for depression and anxiety and their
      factor structures replicated those reported in the literature. Sensitivity and
      specificity analyses showed that the PHQ-9 is sensitive but not specific at
      capturing depressive symptoms when compared to clinician diagnoses whereas the
      GAD-7 was neither sensitive nor specific at capturing anxiety symptoms. The
      implications of these findings are discussed in reference to the scales
      themselves and the cultural specificity of the Lebanese population.

PMID- 27031597
TI  - Properties and ionic self-assembled structures from mixture of a bola-type strong
      alkali dication and a branched phosphoric acid.
AB  - Ionic self-assembled structures have been prepared successfully between di-(2
      ethylhexyl) phosphoric acid (DEHPA) and hexamethonium hydroxide (HMO(OH)2). The
      DEHPA/HMO(OH)2 complexes show good surface activity at a wide mixing molar ratio
      of DEHPA to HMO(OH)2 (rho), within which the critical micellar concentration
      (cmc) is far below that of any single component. In bulk aqueous solutions, rich
      phase behavior was observed by varying cDEHPA and cHMO(OH)2. When the
      concentration of HMO(OH)2 is in the range of 10-100 mmol L(-1), isotropic L1
      phases, birefringent Lalpha phases and a phase-separated region were successively
      observed with increasing cDEHPA. At high cHMO(OH)2 range (>78 mmol L(-1)), a
      narrow L1/Lalpha two-phase region with the Lalpha phase at the bottom was noticed
      between the single L1 and single Lalpha phase regions. The rheological properties
      of the samples in the single Lalpha phase region at 2.6 ? rho ? 2.8 are quite
      similar. Cryo-TEM and freeze-fracture TEM (FF-TEM) observations revealed the
      presence of multilamellar vesicles with flexible and even branched bilayers. At
      2.2 ? rho ? 2.6, however, the rheological properties are highly sensitive to rho
      due to the sophisticated self-assembly behavior as proved by imaging studies and
      (2)H NMR measurements. Closely-stacked flat structures which look like foams or
      cellular networks have been newly discovered. Interestingly, NaCl could arouse an
      L1 to Lalpha phase transition due to the suppression of the effective area of the
      hydrophilic headgroups of the ionic complexes, leading to an increase of the
      critical packing parameter p. The viscoelasticity properties of the salt
      containing Lalpha phases decreased with increasing salinity. We hope our research
      can provide new ideas for the construction of supramolecular materials by
      surfactant ionic self-assembly (SISA) strategy.

PMID- 27031596
TI  - Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics
      against multi-drug resistant clinical bacterial isolates.
AB  - ZnO nanoparticles (ZnONPs) were synthesised through a simple and efficient
      biogenic synthesis approach, exploiting the reducing and capping potential of
      Aloe barbadensis Miller (A. vera) leaf extract (ALE). ALE-capped ZnO
      nanoparticles (ALE-ZnONPs) were characterized using UV-Vis spectroscopy, X-ray
      diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning
      electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and
      transmission electron microscopy (TEM) analyses. XRD analysis provided the
      average size of ZnONPs as 15 nm. FTIR spectral analysis suggested the role of
      phenolic compounds, terpenoids and proteins present in ALE, in nucleation and
      stability of ZnONPs. Flow cytometry and atomic absorption spectrophotometry (AAS)
      data analyses revealed the surface binding and internalization of ZnONPs in Gram
      +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) cells, respectively.
      Significant antibacterial activity of ALE-ZnONPs was observed against extended
      spectrum beta lactamases (ESBL) positive E. coli, Pseudomonas aeruginosa, and
      methicillin resistant S. aureus (MRSA) clinical isolates exhibiting the MIC and
      MBC values of 2200, 2400 MUg/ml and 2300, 2700 MUg/ml, respectively. Substantial
      inhibitory effects of ALE-ZnONPs on bacterial growth kinetics, exopolysaccharides
      and biofilm formation, unequivocally suggested the antibiotic and anti-biofilm
      potential. Overall, the results elucidated a rapid, environmentally benign, cost
      effective, and convenient method for ALE-ZnONPs synthesis, for possible
      applications as nanoantibiotics or drug carriers.

PMID- 27031598
TI  - Fine particulate (PM2.5) dynamics during rapid urbanization in Beijing, 1973
      2013.
AB  - PM2.5 has been given special concern in recent years when the air quality
      monitoring station started recording. However, long-term PM2.5 concentration
      dynamic analysis cannot be taken with the limited observations. We therefore
      estimated the PM2.5 concentration using meteorological visibility data in
      Beijing. We found that 71 +/- 17% of PM10 were PM2.5, which contributed to
      visibility impairment (y = 332.26e(-0.232x); R(2) = 0.75, P < 0.05). We then
      reconstructed a time series of annual PM2.5 from 1973 to 2013, and examined its
      relationship with urbanization by indicators of population, gross domestic
      production (GDP), energy consumption, and number of vehicles. Concluded that 1)
      Meteorological conditions were not the major cause of PM2.5 increase from 1973 to
      2013; 2) With population and GDP growth, PM2.5 increased significantly (R(2) =
      0.5917, P < 0.05; R(2) = 0.5426, P < 0.05); 3) Intensive human activity could
      change air quality in a short period, as observed changes in the correlations of
      PM2.5 concentration with energy consumption and number of vehicles before and
      after 2004, respectively. The success of this research provides an easy way in
      reconstructing long-term PM2.5 concentration with limited PM2.5 observation and
      meteorological visibility, and insight the impact of urbanization on air quality.

PMID- 27031599
TI  - Scientific issues raised by the use of dogs as laboratory animals.

PMID- 27031600
TI  - A comparative evaluation of six principal IgY antibody extraction methods.
AB  - Egg yolk has been considered a promising source of antibodies. Our study was
      designed to compare six principal IgY extraction methods (water dilution,
      polyethylene glycol [PEG] precipitation, caprylic acid extraction, chloroform
      extraction, phenol extraction, and carrageenan extraction), and to assess their
      relative extraction efficiencies and the purity of the resulting antibodies. The
      results showed that the organic solvents (chloroform or phenol) minimised the
      lipid ratio in the egg yolk. The water dilution, PEG precipitation and caprylic
      acid extraction methods resulted in high yields, and antibodies purified with PEG
      and carrageenan exhibited high purity. Our results indicate that phenol
      extraction would be more suitable for preparing high concentrations of IgY for
      non-therapeutic usage, while the water dilution and carrageenan extraction
      methods would be more appropriate for use in the preparation of IgY for oral
      administration. 

PMID- 27031601
TI  - A training course on laboratory animal science: an initiative to implement the
      Three Rs of animal research in India.
AB  - There is a current need for a change in the attitudes of researchers toward the
      care and use of experimental animals in India. This could be achieved through
      improvements in the provision of training, to further the integration of the
      Three Rs concept into scientific research and into the regulations of the
      Committee for the Purpose of Control and Supervision of Experiments on Animals
      (CPCSEA). A survey was performed after participants undertook the Federation of
      European Laboratory Animal Science Associations (FELASA) Category C-based course
      on Laboratory Animal Science (in 2013 and 2015). It revealed that the
      participants subsequently employed, in their future research, the practical and
      theoretical Three Rs approaches that they had learned. This is of great
      importance in terms of animal welfare, and also serves to benefit their research
      outcomes extensively. All the lectures, hands-on practical sessions and
      supplementary elements of the courses, which also involved the handling of small
      animals and procedures with live animals, were well appreciated by the
      participants. Insight into developments in practical handling and welfare
      procedures, norms, directives, and ethical use of laboratory animals in research,
      was also provided, through the comparison of results from the 2013 and 2015 post
      course surveys. 

PMID- 27031602
TI  - Non-human primates in neuroscience research: The case against its scientific
      necessity.
AB  - Public opposition to non-human primate (NHP) experiments is significant, yet
      those who defend them cite minimal harm to NHPs and substantial human benefit.
      Here we review these claims of benefit, specifically in neuroscience, and show
      that: a) there is a default assumption of their human relevance and benefit,
      rather than robust evidence; b) their human relevance and essential contribution
      and necessity are wholly overstated; c) the contribution and capacity of non
      animal investigative methods are greatly understated; and d) confounding issues,
      such as species differences and the effects of stress and anaesthesia, are
      usually overlooked. This is the case in NHP research generally, but here we
      specifically focus on the development and interpretation of functional magnetic
      resonance imaging (fMRI), deep brain stimulation (DBS), the understanding of
      neural oscillations and memory, and investigation of the neural control of
      movement and of vision/binocular rivalry. The increasing power of human-specific
      methods, including advances in fMRI and invasive techniques such as
      electrocorticography and single-unit recordings, is discussed. These methods
      serve to render NHP approaches redundant. We conclude that the defence of NHP use
      is groundless, and that neuroscience would be more relevant and successful for
      humans, if it were conducted with a direct human focus. We have confidence in
      opposing NHP neuroscience, both on scientific as well as on ethical grounds. 

PMID- 27031603
TI  - Statistics of Scientific Procedures on Living Animals 2014: A new format, and
      hopefully a new era of diminishing animal experimentation?
AB  - The Annual Statistics of Scientific Procedures on Living Animals Great Britain
      2014 reports a welcome decline in animal experimentation in the UK. However,
      caution has to be exercised when interpreting these most recent figures, due to
      the significant changes made to satisfy the requirements of Directive 2010/63/EU
      as to what information is reported and how it is reported. Comparisons to the
      figures and trends reported in previous years is difficult, so this paper focuses
      on the specifics of the current report, providing information on overall animal
      use and highlighting specific issues associated with genetically-altered animals,
      fish and primates. There is a detailed discussion of the extent of the changes,
      commenting on the benefits and disadvantages of the new format, in areas such as
      severity of procedures, legislation and techniques of special interest. It also
      considers the consequences of the changes on the effective monitoring of
      laboratory animal use, the openness and transparency regarding the impacts of
      animal use, and the implementation of Three Rs initiatives. In addition,
      suggestions for further improvements to the new format are made to the Home
      Office.

PMID- 27031604
TI  - Brazilian Center for the Validation of Alternative Methods (BraCVAM) and the
      process of validation in Brazil.
AB  - The need for the creation of a Brazilian centre for the validation of alternative
      methods was recognised in 2008, and members of academia, industry and existing
      international validation centres immediately engaged with the idea. In 2012, co
      operation between the Oswaldo Cruz Foundation (FIOCRUZ) and the Brazilian Health
      Surveillance Agency (ANVISA) instigated the establishment of the Brazilian Center
      for the Validation of Alternative Methods (BraCVAM), which was officially
      launched in 2013. The Brazilian validation process follows OECD Guidance Document
      No. 34, where BraCVAM functions as the focal point to identify and/or receive
      requests from parties interested in submitting tests for validation. BraCVAM then
      informs the Brazilian National Network on Alternative Methods (RENaMA) of
      promising assays, which helps with prioritisation and contributes to the
      validation studies of selected assays. A Validation Management Group supervises
      the validation study, and the results obtained are peer-reviewed by an ad hoc
      Scientific Review Committee, organised under the auspices of BraCVAM. Based on
      the peer-review outcome, BraCVAM will prepare recommendations on the validated
      test method, which will be sent to the National Council for the Control of Animal
      Experimentation (CONCEA). CONCEA is in charge of the regulatory adoption of all
      validated test methods in Brazil, following an open public consultation. 

PMID- 27031605
TI  - Why does our concern for animals cease when we leave the laboratory?

PMID- 27031606
TI  - Interpersonal impacts mediate the association between personality and treatment
      response in major depression.
AB  - Personality, as characterized by the Five-Factor Model, predicts response to
      psychotherapy for depression. To explain how personality impacts treatment
      response, the present study investigated patient and therapist interpersonal
      processes in treatment sessions as an explanatory pathway. A clinical trial was
      conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with
      primary major depressive disorder completed 16-20 weeks of cognitive-behavioral
      or interpersonal therapy. Before treatment, patients completed the Revised NEO
      Personality Inventory to assess personality domains (neuroticism, extraversion,
      openness-to-experience, agreeableness, and conscientiousness). After 3 and 13
      weeks, patient interpersonal behavior was rated by the therapist and vice versa
      to determine levels of patient and therapist communal and agentic behaviors.
      Depression levels were measured before and after treatment. Structural equation
      modeling supported that patients' interpersonal behavior during therapy mediated
      the associations between pretreatment personality and depression treatment
      outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse)
      predicted higher levels of patient communion throughout treatment, which was in
      turn associated with improved treatment outcomes. Furthermore, patient
      agreeableness was inversely associated with agency throughout treatment, which
      was linked to poorer treatment response. Therapist interpersonal behavior was not
      a significant mediator. Results suggest that patient interpersonal behavior
      during treatment may be one way that patient personality impacts clinical
      outcomes in depression. Results underscore the clinical utility of Five-Factor
      Model domains in treatment process and outcome. (PsycINFO Database Record 

PMID- 27031607
TI  - Regioselective Synthesis of 3-Hydroxy-4,5-alkyl-Substituted Pyridines Using 1,3
      Enynes as Alkynes Surrogates.
AB  - The poor regioselectivity of the [4 + 2] cycloaddition of 3-azetidinones with
      internal alkynes bearing two alkyl substituents via nickel-catalyzed carbon
      carbon activation is addressed using 1,3-enynes as substrates. The judicious
      choice of substitution on the enyne enables complementary access to each
      regioisomer of 3-hydroxy-4,5-alkyl-substituted pyridines, which are important
      building blocks in medicinal chemistry endeavors. 

PMID- 27031608
TI  - Real-Time Sharing of Zika Virus Data in an Interconnected World.

PMID- 27031609
TI  - A fluorescent HTS assay for phosphohydrolases based on nucleoside 5'
      fluorophosphates: its application in screening for inhibitors of mRNA decapping
      scavenger and PDE-I.
AB  - Several nucleotide-specific phosphohydrolases can cleave P-F bonds in substrate
      analogues containing a fluorophosphate moiety to release fluoride ions. In this
      work, by employing a fluoride-sensitive molecular sensor, we harnessed this
      cleavage reaction to develop a fluorescence assay to screen for phosphohydrolase
      inhibitors. The assay is rapid, sensitive, and based on simple and synthetically
      available reagents. The assay was adapted to the high-throughput screening (HTS)
      format and its utility was demonstrated by screening an 'in-house' library of
      small nucleotides against two enzymes: DcpS, a metal-independent mRNA decapping
      pyrophosphatase of the histidine triad (HIT) family; and PDE-I, a divalent cation
      dependent nuclease. Our screening results agreed with the known specificities of
      DcpS and PDE-I, and led to the selection of several inhibitors featuring low
      micromolar IC50 values. For DcpS, we also verified the results by using an
      alternative method with the natural substrate. Notably, the assay presented here
      is the first fluorescence-based HTS-adaptable assay for DcpS, an established
      therapeutic target for spinal muscular atrophy. The assay should be useful for
      phosphohydrolase specificity profiling and inhibitor discovery, particularly in
      the context of DcpS and other HIT-family enzymes, which play key roles in
      maintaining cellular functions and have been linked to disease development. 

PMID- 27031610
TI  - Exercise as an Intervention to Reduce Study-Related Fatigue among University
      Students: A Two-Arm Parallel Randomized Controlled Trial.
AB  - BACKGROUND: Many university students experience high levels of study-related
      fatigue. This high prevalence, and the negative impact of fatigue on health and
      academic performance, call for prevention and reduction of these symptoms. The
      primary aim of the current study was to investigate to what extent an exercise
      intervention is effective in reducing three indicators of study-related fatigue
      (emotional exhaustion, overall fatigue, and need for recovery). Effects of
      exercise on secondary outcomes (sleep quality, self-efficacy, physical fitness,
      and cognitive functioning) were also investigated. METHODS: Participants were
      students with high levels of study-related fatigue, currently not exercising or
      receiving other psychological or pharmacological treatments, and with no medical
      cause of fatigue. They were randomly assigned to either a six-week exercise
      intervention (low-intensity running three times a week, n = 49) or wait list (no
      intervention, n = 48). All participants were measured before the intervention
      (T0), and immediately after the intervention (T1). Exercisers were also
      investigated 4 weeks (T2) and 12 weeks (T3) after the intervention. RESULTS:
      Participants in the exercise condition showed a larger decrease in two of the
      three indicators of study-related fatigue (i.e., overall fatigue and need for
      recovery) as compared to controls. Additionally, sleep quality and some
      indicators of cognitive functioning improved more among exercisers than among
      controls. No effects were found for self-efficacy, and physical fitness. The
      initial effects of the exercise intervention lasted at follow-up (T2 and T3). At
      12-week follow up (T3), 80% of participants in the exercise condition still
      engaged in regular exercise, and further enhancements were seen for emotional
      exhaustion, overall fatigue, and sleep quality. CONCLUSIONS: These results
      underline the value of low-intensity exercise for university students with high
      levels of study-related fatigue. The follow-up effects that were found in this
      study imply that the intervention has the potential to promote regular exercise
      and accompanying beneficial effects in the longer run. TRIAL REGISTRATION:
      Netherlands Trial Register NTR4412.

PMID- 27031612
TI  - Institutional Conflict of Interest and the Translational Pathway.

PMID- 27031611
TI  - Borderline Personality and the Detection of Angry Faces.
AB  - BACKGROUND: Many studies have assessed emotion recognition in patients with
      Borderline Personality Disorder and considerable evidence has been accumulated on
      patients' ability to categorize emotions. In contrast, their ability to detect
      emotions has been investigated sparsely. The only two studies that assessed
      emotion detection abilities found contradictory evidence on patients' ability to
      detect angry faces. METHODS: To clarify whether patients with Borderline
      Personality Disorder show enhanced detection of angry faces, we conducted three
      experiments: a laboratory study (n = 53) with a clinical sample and two highly
      powered web studies that measured Borderline features (n1 = 342, n2 = 220).
      Participants in all studies completed a visual search paradigm, and the reaction
      times for the detection of angry vs. happy faces were measured. RESULTS:
      Consistently, data spoke against enhanced detection of angry faces in the
      Borderline groups, indicated by non-significant group (Borderline vs. healthy
      control) * target (angry vs. happy) interactions, despite highly satisfactory
      statistical power to detect even small effects. CONCLUSIONS: In contrast to
      emotion categorization, emotion detection appears to be intact in patients with
      Borderline Personality Disorder and individuals high in Borderline features. The
      importance of distinguishing between these two processes in future studies is
      discussed.

PMID- 27031613
TI  - Daughters at Risk of Female Genital Mutilation: Examining the Determinants of
      Mothers' Intentions to Allow Their Daughters to Undergo Female Genital
      Mutilation.
AB  - Female genital mutilation (FGM) is still a common practice in many countries in
      Africa and the Middle East. Understanding the determinants of FGM can lead to
      more active interventions to prevent this harmful practice. The goal of this
      study is to explore factors associated with FGM behavior among Iranian mothers
      and their daughters. Based on Ajzen's theory of planned behavior, we examined the
      predictive value of attitudes, subjective norms, perceived behavioral control and
      several socio-demographic variables in relation to mothers' intentions to
      mutilate their daughters. A paper-and-pencil survey was conducted among 300
      mothers (mean age = 33.20, SD = 9.09) who had at least one daughter and who lived
      in Ravansar, a county in Kermanshah Province in Iran. Structural equation
      modeling was used to investigate the relationships among the study variables. Our
      results indicate that attitude is the strongest predictor of mothers' intentions
      to allow their daughters to undergo FGM, followed by subjective norms. Compared
      to younger mothers, older mothers have more positive attitudes toward FGM,
      perceive themselves as having more control over their behavior and demonstrate a
      greater intention to allow their daughter to undergo FGM. Furthermore, we found
      that less educated mothers and mothers living in rural areas had more positive
      attitudes toward FGM and feel more social pressure to allow FGM. The model
      accounts for 93 percent of the variance in the mothers' intentions to allow their
      daughters to undergo FGM. Intervention programs that want to decrease FGM might
      focus primarily on converting mothers' neutral or positive feelings toward FGM
      into negative attitudes and on alleviating the perceived social pressure to
      mutilate one's daughter. Based on our findings, we provide recommendations about
      how to curtail mothers' intentions to allow their daughters to undergo FGM. 

PMID- 27031614
TI  - Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast
      Agent in Companion Dogs with Naturally Occurring Cancer.
AB  - OBJECTIVES: Companion dogs with naturally occurring cancer serve as an important
      large animal model in translational research because they share strong
      similarities with human cancers. In this study, we investigated a long
      circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography
      (CT) imaging of solid tumors in companion dogs with naturally occurring cancer.
      MATERIALS AND METHODS: The institutional animal ethics committees approved the
      study and written informed consent was obtained from all owners. Thirteen dogs
      (mean age 10.1 years) with a variety of masses including primary and metastatic
      liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the
      study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after
      intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional
      contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior
      to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained
      for each dog prior to admission into the study. RESULTS: Liposomal-I resulted in
      significant (p < 0.05) enhancement and uniform opacification of the vascular
      compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast
      agent was demonstrated. Liposomal-I enabled visualization of primary and
      metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo
      enhanced compared to the surrounding normal parenchyma with improved lesion
      conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a
      heterogeneous pattern of intra-tumoral signal with visibly higher signal
      enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors,
      including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung
      tumors, were visualized with a heterogeneous enhancement pattern in the post-24
      hour scan. CONCLUSIONS: The long circulating liposomal-iodine contrast agent
      enabled prolonged visualization of small and large tumors in companion dogs with
      naturally occurring cancer. The study warrants future work to assess the
      sensitivity and specificity of the Liposomal-I agent in various types of
      naturally occurring canine tumors.

PMID- 27031615
TI  - Normal Lung Quantification in Usual Interstitial Pneumonia Pattern: The Impact of
      Threshold-based Volumetric CT Analysis for the Staging of Idiopathic Pulmonary
      Fibrosis.
AB  - BACKGROUND: Although several computer-aided computed tomography (CT) analysis
      methods have been reported to objectively assess the disease severity and
      progression of idiopathic pulmonary fibrosis (IPF), it is unclear which method is
      most practical. A universal severity classification system has not yet been
      adopted for IPF. OBJECTIVE: The purpose of this study was to test the correlation
      between quantitative-CT indices and lung physiology variables and to determine
      the ability of such indices to predict disease severity in IPF. METHODS: A total
      of 27 IPF patients showing radiological UIP pattern on high-resolution (HR) CT
      were retrospectively enrolled. Staging of IPF was performed according to two
      classification systems: the Japanese and GAP (gender, age, and physiology)
      staging systems. CT images were assessed using a commercially available CT
      imaging analysis workstation, and the whole-lung mean CT value (MCT), the
      normally attenuated lung volume as defined from -950 HU to -701 Hounsfield unit
      (NL), the volume of the whole lung (WL), and the percentage of NL to WL (NL%),
      were calculated. RESULTS: CT indices (MCT, WL, and NL) closely correlated with
      lung physiology variables. Among them, NL strongly correlated with forced vital
      capacity (FVC) (r = 0.92, P <0.0001). NL% showed a large area under the receiver
      operating characteristic curve for detecting patients in the moderate or advanced
      stages of IPF. Multivariable logistic regression analyses showed that NL% is
      significantly more useful than the percentages of predicted FVC and predicted
      diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV
      [odds ratio, 0.73; 95% confidence intervals (CI), 0.48 to 0.92; P < 0.01]; III/IV
      [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio,
      0.79; 95% CI, 0.56 to 0.97; P < 0.05]). CONCLUSION: The measurement of NL% by
      threshold-based volumetric CT analysis may help improve IPF staging.

PMID- 27031616
TI  - Predictive Modelling to Identify Near-Shore, Fine-Scale Seabird Distributions
      during the Breeding Season.
AB  - During the breeding season seabirds are constrained to coastal areas and are
      restricted in their movements, spending much of their time in near-shore waters
      either loafing or foraging. However, in using these areas they may be threatened
      by anthropogenic activities such as fishing, watersports and coastal developments
      including marine renewable energy installations. Although many studies describe
      large scale interactions between seabirds and the environment, the drivers behind
      near-shore, fine-scale distributions are not well understood. For example,
      Alderney is an important breeding ground for many species of seabird and has a
      diversity of human uses of the marine environment, thus providing an ideal
      location to investigate the near-shore fine-scale interactions between seabirds
      and the environment. We used vantage point observations of seabird distribution,
      collected during the 2013 breeding season in order to identify and quantify some
      of the environmental variables affecting the near-shore, fine-scale distribution
      of seabirds in Alderney's coastal waters. We validate the models with observation
      data collected in 2014 and show that water depth, distance to the intertidal
      zone, and distance to the nearest seabird nest are key predictors in the
      distribution of Alderney's seabirds. AUC values for each species suggest that
      these models perform well, although the model for shags performed better than
      those for auks and gulls. While further unexplained underlying localised
      variation in the environmental conditions will undoubtedly effect the fine-scale
      distribution of seabirds in near-shore waters we demonstrate the potential of
      this approach in marine planning and decision making. 

PMID- 27031617
TI  - Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1
      Function.
AB  - Methamphetamine (MA) and neurotransmitter precursors and metabolites such as
      tyramine, octopamine, and beta-phenethylamine stimulate the G protein-coupled
      trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human
      conditions including obesity, schizophrenia, depression, fibromyalgia, migraine,
      and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes
      involved in inflammation and response to infection. In brain, TAAR1 stimulation
      reduces synaptic dopamine availability and alters glutamatergic function. TAAR1
      is also expressed at low levels in heart, and may regulate cardiovascular tone.
      Taar1 knockout mice orally self-administer more MA than wild type and are
      insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous
      single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2
      mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we
      demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1,
      but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of
      recombinant inbred (RI) strains have been used to characterize the genetic
      etiology of diseases, but contrary to expectations, BXDs derived 30-40 years ago
      express only the functional B6 Taar1 allele whereas some more recently derived
      BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose
      subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs
      in human TAAR1 alter its function, resulting in expressed, but functional, sub
      functional and non-functional receptors. Our findings are important for
      identifying a predisposition to human diseases, as well as for developing
      personalized treatment options. 

PMID- 27031618
TI  - Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis.
AB  - OBJECTIVE: This study aimed to examine the prognostic value of overexpressed
      p16INK4a in vulvar cancer. Although the tumor suppressor p16INK4a has been shown
      to be of prognostic value in a wide variety of cancers and precancerous lesions,
      its role in the vulvar cancer is still unclear. METHODS: All publications in
      English language on the association between p16INK4a and clinicopathological
      features of vulvar cancer were searched from Pubmed, Embase, and Web of Science,
      and those in Chinese language were identified manually and online from the China
      National Knowledge Infrastructure. Strict inclusion and exclusion criteria were
      followed. Odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals
      (CIs) were pooled to assess the strength of association. Publication bias was
      estimated using funnel plots and the Egger's regression test. RESULTS: A total of
      17 studies with 2309 patients were included. The p16INK4a overexpression was
      found to correlate significantly with the lower International Federation of
      Gynecology and Obstetrics stage (I+II vs III+IV; OR = 0.60, 95%CI: 0.41-0.86, P =
      0.006), negative lymph node metastasis(negative vs positive; OR = 0.61, 95%CI:
      0.39-0.95, P = 0.029), patient's age <55 (OR = 0.54, 95%CI: 0.31-0.96, P =
      0.034), human papillomavirus-positive status (OR = 0.01, 95%CI: 0.00-0.11,
      P<0.001), and higher overall survival (RR = 0.53, 95%CI = 0.35-0.80, P = 0.003).
      CONCLUSION: The p16INK4a might be associated with a higher survival and indicates
      better prognosis of vulvar cancer.

PMID- 27031619
TI  - Enhanced Methylation Analysis by Recovery of Unsequenceable Fragments.
AB  - Bisulfite sequencing is a valuable tool for mapping the position of 5
      methylcytosine in the genome at single base resolution. However, the associated
      chemical treatment causes strand scission, which depletes the number of
      sequenceable DNA fragments in a library and thus necessitates PCR amplification.
      The AT-rich nature of the library generated from bisulfite treatment adversely
      affects this amplification, resulting in the introduction of major biases that
      can confound methylation analysis. Here, we report a method that enables more
      accurate methylation analysis, by rebuilding bisulfite-damaged components of a
      DNA library. This recovery after bisulfite treatment (ReBuilT) approach enables
      PCR-free bisulfite sequencing from low nanogram quantities of genomic DNA. We
      apply the ReBuilT method for the first whole methylome analysis of the highly AT
      rich genome of Plasmodium berghei. Side-by-side comparison to a commercial
      protocol involving amplification demonstrates a substantial improvement in
      uniformity of coverage and reduction of sequence context bias. Our method will be
      widely applicable for quantitative methylation analysis, even for technically
      challenging genomes, and where limited sample DNA is available. 

PMID- 27031620
TI  - Population Structure, Diversity and Trait Association Analysis in Rice (Oryza
      sativa L.) Germplasm for Early Seedling Vigor (ESV) Using Trait Linked SSR
      Markers.
AB  - Early seedling vigor (ESV) is the essential trait for direct seeded rice to
      dominate and smother the weed growth. In this regard, 629 rice genotypes were
      studied for their morphological and physiological responses in the field under
      direct seeded aerobic situation on 14th, 28th and 56th days after sowing (DAS).
      It was determined that the early observations taken on 14th and 28th DAS were
      reliable estimators to study ESV as compared to 56th DAS. Further, 96 were
      selected from 629 genotypes by principal component (PCA) and discriminate
      function analyses. The selected genotypes were subjected to decipher the pattern
      of genetic diversity in terms of both phenotypic and genotypic by using ESV QTL
      linked simple sequence repeat (SSR) markers. To assess the genetic structure,
      model and distance based approaches were used. Genotyping of 96 rice lines using
      39 polymorphic SSRs produced a total of 128 alleles with the phenotypic
      information content (PIC) value of 0.24. The model based population structure
      approach grouped the accession into two distinct populations, whereas unrooted
      tree grouped the genotypes into three clusters. Both model based and structure
      based approach had clearly distinguished the early vigor genotypes from non-early
      vigor genotypes. Association analysis revealed that 16 and 10 SSRs showed
      significant association with ESV traits by general linear model (GLM) and mixed
      linear model (MLM) approaches respectively. Marker alleles on chromosome 2 were
      associated with shoot dry weight on 28 DAS, vigor index on 14 and 28 DAS.
      Improvement in the rate of seedling growth will be useful for identifying rice
      genotypes acquiescent to direct seeded conditions through marker-assisted
      selection.

PMID- 27031621
TI  - Rift Valley Fever Vaccine Virus Clone 13 Is Able to Cross the Ovine Placental
      Barrier Associated with Foetal Infections, Malformations, and Stillbirths.
AB  - Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects
      domesticated ruminants and occasionally humans. Classical RVF vaccines are based
      on formalin-inactivated virus or the live-attenuated Smithburn strain. The
      inactivated vaccine is highly safe but requires multiple administrations and
      yearly re-vaccinations. Although the Smithburn vaccine provides solid protection
      after a single vaccination, this vaccine is not safe for pregnant animals. An
      alternative live-attenuated vaccine, named Clone 13, carries a large natural
      deletion in the NSs gene which encodes the major virulence factor of the virus.
      The Clone 13 vaccine was previously shown to be safe for young lambs and calves.
      Moreover, a study in pregnant ewes suggested that the vaccine could also be
      applied safely during gestation. To anticipate on a possible future incursion of
      RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and
      pregnant ewes. In line with the guidelines from the World Organisation for Animal
      health (Office International des Epizooties, OIE) and regulations of the European
      Pharmacopeia (EP), these studies were performed with an overdose. Our studies
      with lambs showed that Clone 13 dissemination within vaccinated animals is very
      limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in
      contact sentinels and did not revert to virulence upon animal-to-animal passage.
      Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13
      virus is able to spread to the fetus, resulting in malformations and stillbirths.
      Altogether, our results suggest that Clone 13 can be applied safely in lambs, but
      that caution should be taken when Clone 13 is used in pregnant animals,
      particularly during the first trimester of gestation. 

PMID- 27031622
TI  - New Perspectives on the Charging Mechanisms of Supercapacitors.
AB  - Supercapacitors (or electric double-layer capacitors) are high-power energy
      storage devices that store charge at the interface between porous carbon
      electrodes and an electrolyte solution. These devices are already employed in
      heavy electric vehicles and electronic devices, and can complement batteries in a
      more sustainable future. Their widespread application could be facilitated by the
      development of devices that can store more energy, without compromising their
      fast charging and discharging times. In situ characterization methods and
      computational modeling techniques have recently been developed to study the
      molecular mechanisms of charge storage, with the hope that better devices can be
      rationally designed. In this Perspective, we bring together recent findings from
      a range of experimental and computational studies to give a detailed picture of
      the charging mechanisms of supercapacitors. Nuclear magnetic resonance
      experiments and molecular dynamics simulations have revealed that the electrode
      pores contain a considerable number of ions in the absence of an applied charging
      potential. Experiments and computer simulations have shown that different
      charging mechanisms can then operate when a potential is applied, going beyond
      the traditional view of charging by counter-ion adsorption. It is shown that
      charging almost always involves ion exchange (swapping of co-ions for counter
      ions), and rarely occurs by counter-ion adsorption alone. We introduce a charging
      mechanism parameter that quantifies the mechanism and allows comparisons between
      different systems. The mechanism is found to depend strongly on the polarization
      of the electrode, and the choice of the electrolyte and electrode materials. In
      light of these advances we identify new directions for supercapacitor research.
      Further experimental and computational work is needed to explain the factors that
      control supercapacitor charging mechanisms, and to establish the links between
      mechanisms and performance. Increased understanding and control of charging
      mechanisms should lead to new strategies for developing next-generation
      supercapacitors with improved performances.

PMID- 27031623
TI  - QTL Mapping of Low-Temperature Germination Ability in the Maize IBM Syn4 RIL
      Population.
AB  - Low temperature is the primary factor to affect maize sowing in early spring. It
      is, therefore, vital for maize breeding programs to improve tolerance to low
      temperatures at seed germination stage. However, little is known about maize QTL
      involved in low-temperature germination ability. 243 lines of the intermated
      B73*Mo17 (IBM) Syn4 recombinant inbred line (RIL) population was used for QTL
      analysis of low-temperature germination ability. There were significant
      differences in germination-related traits under both conditions of low
      temperature (12 degrees C/16 h, 18 degrees C/8 h) and optimum temperature (28
      degrees C/24 h) between the parental lines. Only three QTL were identified for
      controlling optimum-temperature germination rate. Six QTL controlling low
      temperature germination rate were detected on chromosome 4, 5, 6, 7 and 9, and
      contribution rate of single QTL explained between 3.39%~11.29%. In addition, six
      QTL controlling low-temperature primary root length were detected in chromosome
      4, 5, 6, and 9, and the contribution rate of single QTL explained between
      3.96%~8.41%. Four pairs of QTL were located at the same chromosome position and
      together controlled germination rate and primary root length under low
      temperature condition. The nearest markers apart from the corresponding QTL (only
      0.01 cM) were umc1303 (265.1 cM) on chromosome 4, umc1 (246.4 cM) on chromosome
      5, umc62 (459.1 cM) on chromosome 6, bnl14.28a (477.4 cM) on chromosome 9,
      respectively. A total of 3155 candidate genes were extracted from nine separate
      intervals based on the Maize Genetics and Genomics Database
      (http://www.maizegdb.org). Five candidate genes were selected for analysis as
      candidates putatively affecting seed germination and seedling growth at low
      temperature. The results provided a basis for further fine mapping, molecular
      marker assisted breeding and functional study of cold-tolerance at the stage of
      seed germination in maize.

PMID- 27031624
TI  - Advantage of the Dissolution/Permeation System for Estimating Oral Absorption of
      Drug Candidates in the Drug Discovery Stage.
AB  - In order to increase the success rate in the development of oral drugs, an in
      vitro method, which can accurately estimate human oral absorption of a large
      variety of compounds from solid formulations, is required in the drug discovery
      stage. A dissolution/permeation (D/P) system is an in vitro system that
      simultaneously evaluates dissolution and permeation processes of drugs
      administered orally. In this study, we have investigated the advantages of a D/P
      system for use in the provisional estimation of human oral absorption of a drug
      (absorbed fraction, Fa) by applying it in its solid state. The D/P system mounted
      with a Madin-Darby canine kidney (MDCK) II cell monolayer was used to
      simultaneously evaluate the dissolved and the permeated amounts (% of dose) of 48
      marketed drugs. Slightly modified, fasted-state simulated intestinal fluid
      (FaSSIFmod, 8 mL) was used as the apical medium of the D/P system. Each test drug
      was applied to the apical side of the D/P system as a suspension at one-hundredth
      of the clinical dose. The apparent permeability coefficient across the MDCK II
      cell monolayer was estimated in a buffer solution (pH 6.5). The octanol/water
      distribution coefficient (Log D) was measured at pH 6.5 by a flask shaking
      method. Transport medium (TM, pH 6.5), a buffer solution removing lecithin and
      taurocholate from FaSSIFmod, was used to determine the solubility at 24 h after
      applying drugs. The solubility in TM was used as a free drug concentration in
      FaSSIFmod. A good correlation was obtained between observed human Fa and the
      permeated amount in the D/P system. When the sigmoidal curve was obtained by the
      curve fitting to the data, the determination coefficient was R(2) = 0.79 and the
      95% interval of the predicted Fa values was about +/-24% for all drugs tested in
      the present study. For comparison, the permeated amount was calculated by
      multiplying the permeability of each drug (in vitro Papp) by the solubility in
      FaSSIFmod. However, the calculated permeated amount showed a lower correlation
      with the observed human Fa compared to the observed permeated amount in the D/P
      system. The ratio of the observed permeated amount to the calculated permeated
      amount was in inverse proportion to the ratio of solubility in FaSSIFmod to
      solubility in TM. This finding suggests the necessity of determining the free
      fraction of the dissolved drug in the gastrointestinal (GI) tract when
      calculating the human Fa. In the case of the D/P system, since applied drugs
      dissolved in FaSSIFmod first, and then only the free fraction permeated the
      membrane, an accurate estimation of the human Fa was possible from only the
      observed permeated amount. This in vitro system is expected to contribute to the
      selection of better compounds for oral use during the lead- and formulation
      optimization processes in the drug discovery stage.

PMID- 27031625
TI  - Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided
      Bone Regeneration Around Standardized Calvarial Defects in Rats: An In Vivo
      Microcomputed Tomographic Analysis.
AB  - The aim of this in vivo microcomputed tomographic (MUCT) study was to compare the
      efficacy of Mucograft (MG) vs resorbable collagen membranes (RCMs) in
      facilitating guided bone regeneration (GBR) around standardized calvarial defects
      in rats. Forty female Wistar albino rats with a mean age and weight of 6 to 9
      weeks and 250 to 300 g, respectively, were used. With the rats under general
      anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A
      standardized calvarial defect with a 4.6-mm diameter was created in the left
      parietal bone. For treatment, the rats were randomly divided into four groups (n
      = 10 per group): (1) defects covered with MG (MG group); (2) defects covered with
      an RCM (RCM group); (3) defects filled with xenograft bone particles and covered
      by MG (MG + bone group); and (4) defects filled with xenograft bone particles and
      covered by an RCM (RCM + bone group). Primary closure was achieved using
      interrupted resorbable sutures. The animals underwent high-resolution, three
      dimensional MUCT scans at baseline and at 2, 4, 6, and 8 weeks after the surgical
      procedures. Data regarding volume and bone mineral density (BMD) of newly formed
      bone (NFB) and bone particles revealed an increase in the volume of NFB in all
      the groups from baseline to 8 weeks. The MG group had the lowest volume of NFB
      (mean +/- standard deviation [SD], 1.32 +/- 0.22 mm(3)). No significant
      differences in mean +/- SD values for volume of NFB were observed between the RCM
      (3.50 +/- 0.24 mm(3)) and MG + bone (3.87 +/- 0.36 mm(3)) groups, but their
      values were significantly lower than that of the RCM + bone group (2.95 +/- 0.15
      mm(3), F = 131.91, dfN = 2, dfD = 27, P < .001). Significant differences in BMD
      of NFB between the groups (F = 332.46, dfN = 3, dfD = 36, P < .001) and during
      different data collection periods (F = 97.04, dfN = 3, dfD = 36, P < .01) were
      observed, with the RCM group having the highest mean +/- SD BMD of NFB (0.42 +/-
      0.05 g/mm(3)). Significant differences in the bone particle volume between the
      RCM + bone and MG + bone groups (F = 91.04, dfN = 1, dfD = 18, P < .05) and at
      different data collection periods (F = 314.12, P < .01) were observed, with the
      RCM + bone group displaying greater reduction in both volume (36.8%) and BMD
      (19.7%) of bone particles. The present in vivo MUCT study demonstrated that RCM
      is better than MG in enhancing new bone formation in rat calvarial standardized
      defects when used in combination with mineralized particulate graft material. 

PMID- 27031626
TI  - Guided Bone Regeneration Using Biphasic Calcium Phosphate With Adjunct
      Recombinant Human Bone Morphogenetic Protein-2 With and Without Collagen Membrane
      in Standardized Calvarial Defects in Rats: A Histologic and Biomechanical
      Analysis.
AB  - This study aimed to assess the efficacy of biphasic calcium phosphate (BCP) with
      adjunct recombinant human bone morphogenetic protein-2 (rhBMP-2), with and
      without collagen membrane (CM), in regeneration of standardized rat calvarial
      defects. Thirty female Wistar albino rats with a mean age of 12 weeks and mean
      weight of 300 g were used. The skin over the calvaria was exposed using a full
      thickness flap. A standardized defect measuring 4.6 mm in diameter was created in
      the parietal bone. The defects were randomly divided into the following groups:
      (1) no treatment (control group); (2) BCP soaked in rhBMP-2 and then covered with
      a resorbable CM; and (3) BCP soaked in rhBMP-2. Following euthanasia, histologic,
      histomorphometric, and biomechanical assessments of the calvarial specimens were
      performed to assess bone regeneration. The results showed islands of newly formed
      bone (NFB) between the defect edges in the control group. NFB was observed
      bridging the defect edges and around the remnants of BCP in the rhBMP-2 + BCP +
      CM group and only around the BCP remnants in the rhBMP-2 + BCP group.
      Histomorphometric analysis revealed a significantly higher mean +/- standard
      deviation (SD) percentage of NFB per defect in the rhBMP-2 + BCP + CM group
      (46.12 +/- 2.56) compared with the control (11.79 +/- 0.75) and rhBMP-2 + BCP
      (26.65 +/- 1.48) groups. Although no differences were found in the hardness and
      elastic modulus (EM) of NFB between the rhBMP-2 + BCP + CM (hardness: 687.78 +/-
      4.74 MPa; EM: 27.71 +/- 0.063 GPa) and the rhBMP-2 + BCP (hardness: 637.65 +/-
      6.32 MPa; EM: 21.49 +/- 0.095 GPa) groups, the biomechanical parameters of NFB in
      the control group (hardness: 286.17 +/- 9.49 MPa; EM: 12.62 +/- 0.048 GPa) were
      significantly less. The experiment demonstrated the efficiency of rhBMP-2 + BCP
      in GBR, wherein the presence of CM leads to a greater percentage of new bone
      formation within standardized calvarial defects. 

PMID- 27031627
TI  - Effect of Corticotomies with Different Instruments on Cranial Bone Biology Using
      an Ex Vivo Calvarial Bone Organ Culture Model System.
AB  - Different corticotomy surgical procedures have been developed to shorten
      orthodontic treatment times by stimulating bone remodeling. Although all
      corticotomy procedures involve physical injury to the bone, the clinical outcomes
      can vary. Using an ex vivo calvarial bone organ culture model system, the authors
      evaluated the biologic response of bone to different corticotomies. Bone injuries
      were generated in 276 calvaria dissected from 5- to 7-day-old neonatal mice using
      a piezoelectric knife, a bur, and a handheld screw device. The responses were
      evaluated using chemical, biochemical, and global histomorphometric analyses.
      Injuries generated by the three approaches induced varying degrees of bone
      remodeling activities; however, the piezoelectric knife led to the most extensive
      impact in both bone resorption and formation models. 

PMID- 27031628
TI  - Real-Time Assessment of Guided Bone Regeneration in Standardized Calvarial
      Defects in Rats Using Bio-Oss With and Without Collagen Membrane: An In Vivo
      Microcomputed Tomographic and Histologic Experiment.
AB  - In vivo microcomputed tomography (MUCT) enables real-time assessment of bone
      regeneration. The aim of this MUCT and histologic experiment was to assess guided
      bone regeneration (GBR) around standardized calvarial defects in rats using
      particulate graft material (Bio-Oss) with and without collagen membranes (CMs).
      Eighteen female Sprague-Dawley rats aged 6 weeks and weighing 300 g were used.
      With the rats under general anesthesia, calvaria were exposed and a full
      thickness standardized defect was created on the parietal bone. For treatment,
      rats were randomly assigned to the following three groups: (1) CM group; (2) Bio
      Oss group; and (3) Bio-Oss + CM group. Bone volume and bone mineral density (BMD)
      of newly formed bone (NFB) and remnant bone particles were measured at baseline
      and 2, 4, 6, and 10 weeks after the operations using real-time in vivo MUCT. At
      10 weeks, all animals were sacrificed and calvarial tissues were assessed
      histologically. In the CM group, a significant increase in mean +/- standard
      deviation (SD) BMD of NFB was observed at 6 weeks (0.32 +/- 0.02 g/mm(3)) (P <
      .01) compared with baseline. In the Bio-Oss group, mean +/- SD volume (3.03 +/-
      0.14 mm(3)) (P < .05) and BMD (0.14 +/- 0.01 g/mm(3)) of NFB significantly
      increased at 6 weeks compared with baseline (P < .01). In the Bio-Oss + CM group,
      mean +/- SD volume (0.98 +/- 0.19 mm(3)) and BMD (0.13 +/- 0.01 g/mm(3)) of NFB
      significantly increased at 4 weeks compared with baseline (P < .01). In th Bio
      Oss + CM group, mean +/- SD volume (3.5 +/- 0.7 mm(3)) and BMD (0.44 +/- 0.03
      g/mm(3)) of remnant bone particles were significantly reduced at 10 weeks
      compared with baseline values (5.8 +/- 0.96 mm(3) and 1.3 +/- 0.02 g/mm(3)) (P <
      .05). Although histologic analysis revealed NFB in all the study groups, the Bio
      Oss + CM group exhibited the most. The results of this study revealed that, in
      real time, new bone formation starts as early as 4 weeks in standardized
      calvarial defects undergoing GBR with Bio-Oss + CM, compared with new bone
      formation at 6 weeks in defects undergoing GBR with Bio-Oss alone. 

PMID- 27031629
TI  - Radiographic and Histologic Evaluation of a Bone Void that Formed After
      Recombinant Human Bone Morphogenetic Protein-2-Mediated Sinus Graft Augmentation:
      A Case Report.
AB  - In the present case report, the authors describe radiographic and histologic
      observations of a bone void that formed after a sinus augmentation using a graft
      material that contained recombinant human bone morphogenetic protein-2 (rhBMP-2)
      and discuss clinical and histologic implications of their findings. Sinus
      augmentation was performed using a graft material comprising 1 g of
      hydroxyapatite/beta-tricalcium phosphate, which contained 1 mg of rhBMP-2.
      Radiographic evaluation was conducted with panoramic radiographs and computed
      tomography images of the augmented maxillary sinus, which were analyzed using a
      three-dimensional image-reconstruction program. Histologic evaluation was also
      performed on a biopsy specimen obtained 6 months after the sinus augmentation.
      The total augmented volume increased from 1,582.2 mm(3) immediately after the
      sinus augmentation to 3,344.9 mm3 at 6 months after the augmentation because of
      the formation of a bone void. Twenty-six months after the sinus augmentation, the
      bone void remained but had reduced in volume, with the total augmented volume
      reduced to 2,551.7 mm(3). Histologically, new bone was observed to be in contact
      with the grafted particles, and a fatty marrow-like tissue was present in the
      area of the bone void. This case report shows that the bone void that had formed
      after sinus augmentation resolved over time and seemed to be partially replaced
      with new bone. Furthermore, none of the implants failed, and clinical adverse
      events were not observed during the follow-up period. 

PMID- 27031630
TI  - Bone Regeneration Using Bone Morphogenetic Protein-2 and Biphasic Calcium
      Phosphate With and Without Collagen Membrane in Calvarial Standardized Defects:
      An In Vivo Microcomputed Tomographic Experiment in Rats.
AB  - The aim of this in vivo microcomputed tomographic (MUCT) experiment was to assess
      in real time the efficacy of a combination of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) and biphasic calcium phosphate (BCP), with and
      without resorbable collagen membrane (CM), in regeneration of standardized
      calvarial defects (SCDs) in rats. A total of 30 female Wistar albino rats (n =
      10/group) with a mean age and weight of 7.5 months and 275 g, respectively, were
      used. With the rats under general anesthesia, the calvaria were exposed using
      full-thickness periosteal flaps and unilateral SCDs of 4.6 mm diameter were
      created on the left parietal bone. Defects were left untreated (control group) or
      randomly filled with either BCP soaked in rhBMP-2 and then covered with CM (BMP +
      BCP + CM group) or BCP soaked in rhBMP-2 alone (BMP + BCP group). In vivo MUCT
      scans were done at baseline and 2, 4, 6, and 8 weeks. Newly formed bone (NFB) and
      remaining BCP particles were assessed for their volumes (NFBV, BCPV,
      respectively) and mineral densities (NFBMD, BCPMD, respectively). In vivo MUCT
      results showed scanty amounts of new bone at the peripheries of the defect in the
      control group. In the other two groups, near complete defect closure was evident
      at 8 weeks. The mean NFBV after 8 weeks was 4.63 +/- 0.96 mm(3), 11.82 +/- 1.17
      mm(3), and 13.85 +/- 1.89 mm(3) for the control, BMP + BCP + CM, and BMP + BCP
      groups, respectively. After 8 weeks, the mean NFBMD was 0.38 +/- 0.03 g/mm(3),
      0.24 +/- 0.07 g/mm(3), and 0.35 +/- 0.03 g/mm(3) for the control, BMP + BCP + CM,
      and BMP + BCP groups, respectively. After 8 weeks, the mean BCPV and BCPMD values
      for the BMP + BCP + CM and BMP + BCP groups were 2.73 +/- 0.65 mm(3), 0.33 +/-
      0.08 g/mm(3), 2.49 +/- 0.71 mm(3), and 0.28 +/- 0.03 g/mm(3), respectively. The
      present real-time in vivo MUCT experiment demonstrated that BMP + BCP, either
      with or without CM, was effective in promoting bone regeneration within rat SCDs
      and enabled new bone formation starting as early as 2 weeks. 

PMID- 27031631
TI  - Real-Time Assessment of Guided Bone Regeneration in Standardized Calvarial
      Defects Using a Combination of Bone Graft and Platelet-Derived Growth Factor With
      and Without Collagen Membrane: An In Vivo Microcomputed Tomographic and
      Histologic Experiment in Rats.
AB  - The aim of the present in vivo microcomputed tomography (MUCT) and histologic
      experiment was to assess the efficacy of guided bone regeneration (GBR) around
      standardized calvarial defects using recombinant human platelet-derived growth
      factor (rhPDGF) with and without resorbable collagen membrane (RCM). A total of
      50 female Wistar albino rats with a mean age of 7.5 months and mean weight of 275
      g were used. The calvarium was exposed following midsagittal scalp incision and
      flap reflection. A full-thickness standardized calvarial defect (4.6 mm diameter)
      was created. Study animals were randomly divided into five groups based on
      biomaterials used for GBR within the defect: (1) no treatment (negative control),
      (2) bone graft alone (BG), (3) bone graft covered by RCM (BG + RCM), (4) bone
      graft soaked in rhPDGF (BG + rhPDGF), and (5) bone graft soaked in rhPDGF and
      covered with RCM (BG + rhPDGF + RCM). In vivo MUCT for determination of newly
      formed bone volume (NFBV) and mineral density (NFBMD) and remnant bone particles
      volume (RBPV) and mineral density (RBPMD) was done at baseline and at 2, 4, 6,
      and 8 weeks postoperatively. Eight weeks following surgery, the animals were
      sacrificed and harvested calvarial specimens were subjected to histologic and
      biomechanical analysis. There was an increase in NFBV and NFBMD associated with a
      corresponding decrease in RBPV and RBPMD in all the study groups. Two-way
      analysis of variance revealed significant differences in the measured values
      within and between the groups across the timelines examined during the study
      period (P < .05). While the NFBV was significantly higher in the bone graft, BG +
      RCM, and BG + rhPDGF + RCM groups, the NFBMD was similar in all the groups except
      negative control. The greatest decreases in RBPV and RBPMD were observed in the
      BG + rhPDGF + RCM group in comparison to the other groups. Similarly, BG + rhPDGF
      + RCM groups had hardness and elastic modulus similar to that of natural bone.
      The in vivo MUCT results were validated by the qualitative histologic findings.
      In real time, new bone formation starts as early as 2 weeks in rat calvarial
      defects treated with bone graft and rhPDGF, irrespective of the presence or
      absence of RCM. 

PMID- 27031632
TI  - Efficacy of Mesenchymal Stem Cells as Adjunct to Guided Bone Regeneration in
      Standardized Calvarial Defects in Rats: An In Vivo Microcomputed Tomographic and
      Histologic Analysis.
AB  - The aim of the present in vivo microcomputed tomographic (MUCT), histologic, and
      biomechanical study was to assess the efficacy of bone marrow-derived mesenchymal
      stem cells (BMSCs) for promoting guided bone regeneration (GBR) in a standardized
      rat calvarial defect model. Forty female Wistar albino rats with a mean age of
      7.5 months and mean weight of 275 g were used. Following calvarial exposure under
      general anesthesia, a full-thickness standardized calvarial defect (4.6 mm in
      diameter) was created. The study animals were randomly divided into four groups
      based on biomaterials used for GBR: (1) no treatment (negative control); (2) bone
      graft alone; (3) bone graft placed in the defect and covered with a collagen
      membrane (CM); and (4) bone graft soaked in BMSCs and covered with a CM. Bone
      volume and bone mineral density (BMD) of newly formed bone (NFB) and remnant bone
      particles were determined at baseline and at 2, 4, 6, 8, and 24 weeks
      postoperative using real time in vivo MUCT. Histologic and biomechanical analyses
      of calvarial specimens were performed at 24 weeks, when the rats were euthanized.
      Statistically significant differences in volume and BMD of NFB were observed
      between and within the groups at different data collection periods. Significant
      increases in volume and BMD of NFB occurred as early as week 2 in all groups
      except the negative control. While the greatest volume of NFB was observed in the
      bone graft + BMSC + CM group, BMD of NFB was significantly higher in the bone
      graft + CM group. Statistically significant decreases in volume and BMD of
      remnant bone particles were also observed between the groups. Histologic analysis
      revealed NFB in all groups. The hardness and elastic modulus of NFB in the bone
      graft + BMSC + CM group were significantly higher than that in the other groups
      and also similar to adjacent natural bone. This study shows that using adjunct
      BMSCs with bone graft and CM for guided bone regeneration in standardized rat
      calvarial defects resulted in the highest quality and quantity of NFB.

PMID- 27031633
TI  - Cell Response to Surfaces: A Concise Summary.
AB  - Surface nano- and microtexturing techniques have been used to enhance
      osseointegration, but how these surfaces work is not well understood. Using the
      knowledge gained from the cell and molecular biology fields, tissue engineering
      studies, and their own work, the authors and other researchers have developed
      surfaces for in vitro and in vivo control of the function of cells and tissues.
      In the present article, the authors summarize what they know about the process of
      cell response to surfaces, and what they have done and can do to develop surfaces
      that control hard- and soft-tissue formation and integration of implants. This
      article is intended to add to the clinician's understanding of cell and surface
      interactions, explain why certain surfaces are currently used, and describe what
      surfaces clinicians may see in the future. 

PMID- 27031634
TI  - Evaluation of Different Combinations of Biphasic Calcium Phosphate and Growth
      Factors for Bone Formation in Calvarial Defects in a Rabbit Model.
AB  - The aim of the present preclinical study was to investigate the capability of a
      new formulation of biphasic calcium phosphate (BCP) in achieving new bone
      formation either by itself or in combination with different concentrations of
      growth factors. Twenty-four 3-month-old male New Zealand white rabbits (weight
      range, 2.5 to 3.0 kg) that had been bred exclusively for biomedical research
      purposes and obtained from a licensed vendor were used. Four calvarial defects
      were created in each animal, for a total of 96 defects. Each defect received
      alloplastic BCP (Osteon III, Genoss) that was composed of 60% hydroxyapatite and
      40% beta-tricalcium phosphate) (porosity, ~80%; macropore size, 200 to 400 MUm;
      crystallinity, 95%) combined with different concentrations of recombinant human
      platelet-derived growth factor BB (rhPDGF-BB), human recombinant basic fibroblast
      growth factor-2 (rhFGF-2), or recombinant human bone morphogenetic protein-2
      (rhBMP-2). A custom-made polycarbonate tube was fixed to each defect site by
      applying slight pressure, and a mixture of bone graft and growth factor was
      implanted into the tubes. Data were collected 2, 4, and 8 weeks after creation of
      the defects to assess early and late healing. Various amounts of newly formed
      bone and remnant BCP particles formed inside of the tube throughout the study
      period. The BCP + 0.5 mg/mL rhBMP-2 group exhibited the most bone formation. At 8
      weeks, more new bone formation was noted in the Osteon III + rhBMP-2 combined
      group than in other groups. The present study results indicate that BCP can be
      combined with different concentrations of rhBMP-2, rhFGF-2, and rhPDGF-BB to
      produce new bone formation within a polycarbonate tube in calvarial defects in a
      rabbit model. 

PMID- 27031635
TI  - Guided Bone Regeneration in Standardized Calvarial Defects in Rats Using Bio-Oss
      and beta-Tricalcium Phosphate with Adjunct Platelet-Derived Growth Factor
      Therapy: A Real-Time In Vivo Microcomputed Tomographic, Biomechanical, and
      Histologic Analysis.
AB  - The objective of the present real-time in vivo experiment was to assess guided
      bone regeneration (GBR) in standardized calvarial defects using particulate graft
      material (Bio-Oss) and beta-tricalcium phosphate (beta-TCP) with adjunct
      recombinant human platelet-derived growth factor (rhPDGF) therapy. Eighteen
      female Sprague-Dawley rats with a mean age and weight of 8 +/- 0.53 weeks and 250
      +/- 0.49 g, respectively, were used. Following surgical exposure, a full
      thickness standardized calvarial defect was created on the parietal bone using a
      trephine drill with an outer diameter of 4.6 mm. For treatment, rats were
      randomly divided into three groups (six rats per group): (1) control; (2) rhPDGF
      + Bio-Oss, and (3) rhPDGF + beta-TCP. Volume of newly formed bone (NFB), bone
      mineral density (BMD) of NFB, volume of remnant bone particles, and BMD of
      remnant bone particles were assessed using in vivo microcomputed tomography.
      Measurements were made at baseline and at 2, 4, 6, and 10 weeks after the
      surgical procedures. At 10 weeks, all animals were sacrificed and calvarial
      tissues were assessed histologically. In the control group, a significant
      increase in BMD of NFB was observed at 6 weeks (mean +/- standard deviation [SD],
      0.32 +/- 0.002 g/mm(3)) (P < .01) from baseline, and the defect did not
      regenerate completely. In the rhPDGF + Bio-Oss group, mean +/- SD volume (2.40 +/
      0.25 mm(3)) (P < .01) and BMD (0.13 +/- 0.01 g/mm(3)) of NFB significantly
      increased at 4 weeks and 6 weeks, respectively, from baseline (P < .001). In the
      rhPDGF + beta-TCP group, mean +/- SD volume (2.01 +/- 0.7 mm(3)) and BMD (0.12 +/
      0.02 g/mm(3)) of NFB significantly increased at 4 weeks from baseline (P < .01).
      In the rhPDGF + Bio-Oss and rhPDGF + beta-TCP groups, mean +/- SD BMD of remnant
      bone particles (0.31 +/- 0.11 g/mm(3) and 0.23 +/- 0.01 g/mm(3)) showed
      significant reduction at 6 and 10 weeks, respectively, compared with baseline
      values (1.12 +/- 0.06 g/mm(3) and 0.92 +/- 0.01 g/mm(3), respectively) (P <
      .001). Histologic results at 10 weeks showed NBF in the rhPDGF + Bio-Oss and
      rhPDGF + beta-TCP groups. In real time assessment, when rhPDGF was added to beta
      TCP, BMD and bone hardness significantly increased compared with the other two
      groups. 

PMID- 27031636
TI  - Choukroun Platelet-Rich Fibrin as an Autogenous Graft Biomaterial in Preimplant
      Surgery: Results of a Preliminary Randomized, Human Histomorphometric, Split
      Mouth Study.
AB  - This study aimed to test the null hypothesis that platelet-rich fibrin (PRF), as
      an immediate postextraction graft material, produces bone that is
      histomorphometrically no different than bone derived from healing without
      intervention. The authors compared split-mouth human bone biopsy specimens
      derived from PRF with bone that had healed without intervention. Eight human bone
      biopsies were successfully harvested from four patients. The mean +/- standard
      deviation (SD) percent of newly formed osteoid was 9.9% +/- 5.9% for specimens
      derived from PRF, and 4% +/- 2.1% for specimens derived from the control sites (P
      = .089; 95% confidence interval [CI] 4.5-18.1 and 1.6-6.6, respectively). Mean +/
      SD percent of new mineralized bone was 40.8% +/- 10.3% for the PRF specimens and
      43.9% +/- 16.8% for the control specimens (P = .72, 95% CI, 33.4-55.6 and 19.3
      55.5, respectively). Newly formed bone to fibrovascular tissue ratios for
      specimens in the PRF and control groups were 51%:49% and 48%:52%, respectively.
      Within the limitations of this study, the null hypothesis could not be rejected.
      Bone derived from PRF histologically did not differ from bone that healed without
      intervention. 

PMID- 27031637
TI  - Survival and Success Rates of Dental Implants Placed Using Osteotome Sinus Floor
      Elevation Without Added Bone Grafting: A Retrospective Study with a Follow-up of
      up to 10 Years.
AB  - This retrospective study with a follow-up period of 4 months to 10 years
      evaluated survival, success, and complication rates of implants placed using
      osteotome sinus floor elevation (OSFE) without added bone grafting. A total of
      926 implants were placed, including 530 short implants (6 mm to 8.5 mm) and 209
      implants in low residual bone height (RBH) (< 5 mm). Bone levels were evaluated
      at approximately 3 months and at 1, 3, and 5 years, and in some cases up to 10
      years after implants were placed. The implant survival rate was 98.3% at the 5
      year follow-up. Twelve of the 926 implants failed (6 preprosthetic, 6
      postprosthetic). The success rate was 95.4% at a threshold of less than 1 mm of
      bone loss for combined systems (Straumann; Nobel Biocare). Short implant survival
      and success rates were statistically comparable to conventional-length implants.
      Low-RBH implants had a lower but acceptable survival rate of 95.7%. Adverse
      events were rare, with one case of infection and zero cases of vertigo reported.
      The findings of this study indicate that implant placement with OSFE without
      added bone graft is highly successful, even when short implants are used in low
      RBH. 

PMID- 27031638
TI  - Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided
      Bone Regeneration Around Standardized Calvarial Defects in Rats: A Histologic and
      Biomechanical Assessment.
AB  - Guided bone regeneration (GBR) using a porcine-derived collagen matrix (Mucograft
      [MG], Geistlich) has not yet been reported. The aim of this histologic and
      biomechanical study was to compare the efficacy of MG versus resorbable collagen
      membranes (RCMs) in facilitating GBR around standardized rat calvarial defects.
      Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and
      250 to 300 g, respectively, were used. With the rats under general anesthesia,
      the skin over the calvaria was exposed using a full-thickness flap. A 4.6-mm
      diameter standardized calvarial defect was created in the left parietal bone. For
      treatment, the rats were randomly divided into four groups (n = 10 per group):
      (1) MG group: the defect was covered with MG; (2) RCM group: the defect was
      covered with an RCM; (3) MG + bone group: the defect was filled with bone graft
      particles and covered by MG; and (4) RCM + bone group: the defect was filled with
      bone graft particles and covered by an RCM. Primary closure was achieved using
      interrupted resorbable sutures. The animals were sacrificed at 8 weeks after the
      surgical procedures. Qualitative histologic analysis and biomechanical assessment
      to identify hardness and elastic modulus of newly formed bone (NFB) were
      performed. Collected data were statistically analyzed using one-way analysis of
      variance. Histologic findings revealed NFB with fibrous connective tissue in all
      groups. The quantity of NFB was highest in the RCM + bone group. Statistically
      significant differences in the hardness (F = 567.69, dfN = 3, dfD = 36, P < .001)
      and elastic modulus (F = 294.19, dfN = 3, dfD = 36, P < .001) of NFB were found
      between the groups. Although the RCM + bone group had the highest mean +/-
      standard deviation (SD) hardness of NFB (531.4 +/- 24.9 MPa), the RCM group had
      the highest mean +/- SD elastic modulus of NFB (18.63 +/- 1.89 GPa). The present
      study demonstrated that RCMs are better than MG at enhancing new bone formation
      in standardized rat calvarial defects when used along with mineralized
      particulate graft material. 

PMID- 27031640
TI  - Correction: Possible Role of Arginase-1 in Concomitant Tumor Immunity.

PMID- 27031639
TI  - Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus
      Isolates.
AB  - The soil-related Bacillus and Paenibacillus species have increasingly been
      implicated in various human diseases. Nevertheless, their identification still
      poses problems in the clinical microbiology laboratory and, with the exception of
      Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity
      for humans. In this study, we evaluated the use of matrix-assisted laser
      desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in the
      identification of clinical isolates of these genera and conducted genotypic and
      phenotypic analyses to highlight specific virulence properties. Seventy-five
      clinical isolates were subjected to biochemical and MALDI-TOF MS identification.
      16S rDNA sequencing and supplemental tests were used to solve any discrepancies
      or failures in the identification results. MALDI-TOF MS significantly
      outperformed classical biochemical testing for correct species identification and
      no misidentification was obtained. One third of the collected strains belonged to
      the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were
      isolated at high rate. Antimicrobial susceptibility testing showed that all the
      B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus
      glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The
      evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm
      formation revealed that B. cereus displays the highest virulence potential.
      However, although generally considered nonpathogenic, most of the other species
      were shown to swim, swarm, produce biofilms, and secrete proteases that can have
      a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for
      fast and accurate identification of Bacillus and Paenibacillus strains whose
      virulence properties make them of increasing clinical relevance. 

PMID- 27031641
TI  - DTW-MIC Coexpression Networks from Time-Course Data.
AB  - When modeling coexpression networks from high-throughput time course data,
      Pearson Correlation Coefficient (PCC) is one of the most effective and popular
      similarity functions. However, its reliability is limited since it cannot capture
      non-linear interactions and time shifts. Here we propose to overcome these two
      issues by employing a novel similarity function, Dynamic Time Warping Maximal
      Information Coefficient (DTW-MIC), combining a measure taking care of functional
      interactions of signals (MIC) and a measure identifying time lag (DTW). By using
      the Hamming-Ipsen-Mikhailov (HIM) metric to quantify network differences, the
      effectiveness of the DTW-MIC approach is demonstrated on a set of four synthetic
      and one transcriptomic datasets, also in comparison to TimeDelay ARACNE and
      Transfer Entropy. 

PMID- 27031642
TI  - Association between Types of Chronic Conditions and Cancer Stage at Diagnosis
      among Elderly Medicare Beneficiaries with Prostate Cancer.
AB  - The current retrospective observational study was conducted to examine the
      association between types of chronic conditions and cancer stage at diagnosis
      among elderly Medicare beneficiaries with prostate cancer using the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare linked database. The study cohort
      consisted of elderly men (>=66 years) with prostate cancer diagnosed between 2002
      and 2009 (N = 103,820). Cancer stage at diagnosis (localized versus advanced) was
      derived using the American Joint Committee on Cancer classification. Chronic
      conditions were identified during the year before cancer diagnosis and classified
      as: (1) only cardiometabolic (CM); (2) only mental health (MH); (3) only
      respiratory (RESP); (4) CM + MH; (5) CM + RESP; (6) MH + RESP; (7) CM+ MH + RESP;
      and (8) none of the 3 types of conditions. Chi-square tests and multivariable
      logistic regressions were used to test the unadjusted and adjusted associations
      between types of chronic conditions and cancer stage at diagnosis. The highest
      percentage (5.8%) of advanced prostate cancer was observed among elderly men with
      none of the 3 types of chronic conditions (CM, RESP, MH). In the adjusted
      logistic regression, those with none of the 3 types of chronic conditions were
      44% more likely to be diagnosed with advanced prostate cancer compared to men
      with all the 3 types of chronic conditions. Elderly men without any of the
      selected chronic conditions were more likely to be diagnosed with advanced
      prostate cancer; therefore, strategies to reduce the risk of advanced prostate
      cancer should be targeted toward elderly men without these conditions.

PMID- 27031643
TI  - The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is
      Determined by Their Physicochemical Properties.
AB  - Complex engineered nanomaterials (CENs) are a rapidly developing class of
      structurally and compositionally complex materials that are expected to dominate
      the next generation of functional nanomaterials. The development of methods
      enabling rapid assessment of the toxicity risk associated with this type of
      nanomaterial is therefore critically important. We evaluated the toxicity of
      three differently structured nickel-silica nanomaterials as prototypical CENs:
      simple, surface-deposited Ni-SiO2 and hollow and non-hollow core-shell Ni@SiO2
      materials (i.e., ~1-2 nm Ni nanoparticles embedded into porous silica shells with
      and without a central cavity, respectively). Zebrafish embryos were exposed to
      these CENs, and morphological (survival and malformations) and physiological
      (larval motility) endpoints were coupled with thorough characterization of
      physiochemical characteristics (including agglomeration, settling and nickel ion
      dissolution) to determine how toxicity differed between these CENs and equivalent
      quantities of Ni2+ salt (based on total Ni). Exposure to Ni2+ ions strongly
      compromised zebrafish larva viability, and surviving larvae showed severe
      malformations. In contrast, exposure to the equivalent amount of Ni CEN did not
      result in these abnormalities. Interestingly, exposure to Ni-SiO2 and hollow
      Ni@SiO2 provoked abnormalities of zebrafish larval motor function, indicating
      developmental toxicity, while non-hollow Ni@SiO2 showed no toxicity. Correlating
      these observations with physicochemical characterization of the CENs suggests
      that the toxicity of the Ni-SiO2 and hollow Ni@SiO2 material may result partly
      from an increased effective exposure at the bottom of the well due to rapid
      settling. Overall, our data suggest that embedding nickel NPs in a porous silica
      matrix may be a straightforward way to mitigate their toxicity without
      compromising their functional properties. At the same time, our results also
      indicate that it is critical to consider modification of the effective exposure
      when comparing different nanomaterial configurations, because effective exposure
      might influence NP toxicity more than specific "nano-chemistry" effects. 

PMID- 27031645
TI  - Improving Precision and Accuracy of Isotope Ratios from Short Transient Laser
      Ablation-Multicollector-Inductively Coupled Plasma Mass Spectrometry Signals:
      Application to Micrometer-Size Uranium Particles.
AB  - The isotope drift encountered on short transient signals measured by
      multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) is related
      to differences in detector time responses. Faraday to Faraday and Faraday to ion
      counter time lags were determined and corrected using VBA data processing based
      on the synchronization of the isotope signals. The coefficient of determination
      of the linear fit between the two isotopes was selected as the best criterion to
      obtain accurate detector time lag. The procedure was applied to the analysis by
      laser ablation-MC-ICPMS of micrometer sized uranium particles (1-3.5 MUm). Linear
      regression slope (LRS) (one isotope plotted over the other), point-by-point, and
      integration methods were tested to calculate the (235)U/(238)U and (234)U/(238)U
      ratios. Relative internal precisions of 0.86 to 1.7% and 1.2 to 2.4% were
      obtained for (235)U/(238)U and (234)U/(238)U, respectively, using LRS
      calculation, time lag, and mass bias corrections. A relative external precision
      of 2.1% was obtained for (235)U/(238)U ratios with good accuracy (relative
      difference with respect to the reference value below 1%). 

PMID- 27031644
TI  - The Male Fetal Biomarker INSL3 Reveals Substantial Hormone Exchange between
      Fetuses in Early Pig Gestation.
AB  - The peptide hormone INSL3 is uniquely produced by the fetal testis to promote the
      transabdominal phase of testicular descent. Because it is fetal sex specific, and
      is present in only very low amounts in the maternal circulation, INSL3 acts as an
      ideal biomarker with which to monitor the movement of fetal hormones within the
      pregnant uterus of a polytocous species, the pig. INSL3 production by the fetal
      testis begins at around GD30. At GD45 of the ca. 114 day gestation, a time at
      which testicular descent is promoted, INSL3 evidently moves from male to female
      allantoic compartments, presumably impacting also on the female fetal
      circulation. At later time-points (GD63, GD92) there is less inter-fetal
      transfer, although there still appears to be significant INSL3, presumably of
      male origin, in the plasma of female fetuses. This study thus provides evidence
      for substantial transfer of a peptide hormone between fetuses, and probably also
      across the placenta, emphasizing the vulnerability of the fetus to extrinsic
      hormonal influences within the uterus. 

PMID- 27031646
TI  - Niabella aquatica sp. nov., isolated from lake water.
AB  - A Gram-reaction-negative, strictly aerobic, non-motile, yellow and rod-shaped
      bacterium (designated RP-2T) isolated from lake water, was characterized by a
      polyphasic approach to clarify its taxonomic position. Strain RP-2T was observed
      to grow optimally at 30  degrees C and at pH 7.0 on R2A medium. Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that RP-2T represented a
      member of the genus Niabella of the family Chitinophagaceae and was most closely
      related to Niabella yanshanensis KACC 14980T (96.6 %), Niabella ginsengisoliKACC
      13021T (96.5 %), Niabella drilacis DSM 25811T (95.7 %) and Niabella aurantiaca
      KACC 11698T (95.6 %). The DNA G+C content was 44.5 mol%. The major polar lipids
      were diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE). The
      predominant quinone was MK-7. The major fatty acids were iso-C15:0, iso-C15:1G,
      iso-C17:0 3-OH and summed feature 3 (comprising C16:1omega7c and/or C16:1omega6c)
      supported the affiliation of RP-2T to the genus Niabella. However, RP-2T could be
      distinguished genotypically and phenotypically from the species of the genus
      Niabella with validly published names. The novel isolate therefore represents a
      novel species, for which the name Niabella aquatica sp. nov. is proposed, with
      the type strain RP-2T (=KACC 18623T =JCM 30952T). 

PMID- 27031647
TI  - Halanaeroarchaeum sulfurireducens gen. nov., sp. nov., the first obligately
      anaerobic sulfur-respiring haloarchaeon, isolated from a hypersaline lake.
AB  - Anaerobic enrichments with acetate as electron donor and carbon source, and
      elemental sulfur as electron acceptor at 4 M NaCl using anaerobic sediments and
      brines from several hypersaline lakes in Kulunda Steppe (Altai, Russia) resulted
      in isolation in pure culture of four strains of obligately anaerobic haloarchae
      growing exclusively by sulfur respiration. Such metabolism has not yet been
      demonstrated in any known species of Halobacteria, and in the whole archaeal
      kingdom, acetate oxidation with sulfur as acceptor was not previously
      demonstrated. The four isolates had nearly identical 16S rRNA gene sequences and
      formed a novel genus-level branch within the family Halobacteriaceae. The strains
      had a restricted substrate range limited to acetate and pyruvate as electron
      donors and elemental sulfur as electron acceptor. In contrast to aerobic
      haloarchaea, the biomass of anaerobic isolates completely lacked the typical red
      pigments. Growth with acetate+sulfur was observed between 3-5 M NaCl and at a pH
      range from 6.7 to 8.0. The membrane core lipids were dominated by archaeols. On
      the basis of distinct physiological and phylogenetic data, the sulfur-respiring
      isolates represent a novel species of a new genus in the family Halobacteriaceae,
      for which the name Halanaeroarchaeaum sulfurireducens gen. nov., sp. nov. is
      proposed. The type strain of the type species is HSR2T (=JCM 30661T=UNIQEM
      U935T). 

PMID- 27031648
TI  - Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal
      Pathway at Different Stages of Development.
AB  - OBJECTIVE: The development of retinotectal pathways form precise topographical
      maps is usually completed by the third postnatal week. Cytokines participate in
      the development and plasticity of the nervous system. We have previously shown
      that in vivo treatment with interleukin 2 disrupts the retinocollicular
      topographical order in early stages of development. Therefore, we decided to
      study the effect of a single intravitreous injection of IL-6 upon retinotectal
      circuitry in neonates and juvenile rats. MATERIALS AND METHODS: Lister Hooded
      rats received an intravitreous injection of IL-6 (50 ng/ml) or vehicle (PBS) at
      either postnatal day (PND)10 or PND30 and the ipsilateral retinotectal pathway
      was evaluated 4 or 8 days later, respectively. RESULTS: Our data showed that, at
      different stages of development, a single IL-6 intravitreous treatment did not
      produce an inflammatory response and increased retinal axon innervation
      throughout the visual layers of the superior colliculus. CONCLUSIONS: Taken
      together, our data provide the first evidence that a single intravitreous
      injection with IL-6 leads to sprouting in the subcortical visual connections and
      suggest that small changes in IL-6 levels might be sufficient to impair the
      correct neuronal circuitry fine-tuning during brain development.

PMID- 27031649
TI  - A Randomized, Clinical Trial Involving Different Surgical Methods Affecting the
      Sphincter of Oddi in Patients With Choledocholithiasis.
AB  - AIM: The purpose of the current study was to compare pressure changes in the
      sphincter of Oddi (SO) and stone recurrence after surgery in patients with
      choledocholithiasis who underwent laparoscopic common bile duct exploration
      during laparoscopic cholecystectomy (LC) or endoscopic sphincterotomy (EST) with
      LC, which may provide clinical evidence for choledocholithiasis patients to
      choose the appropriate surgical approach. MATERIALS AND METHODS: Fifty-one
      patients with choledocholithiasis were randomized to the EST/LC (group A 26
      cases) or laparoscopic common bile duct exploration during LC group (group B 25
      cases). We performed SO manometry during surgery and 3 months postoperatively on
      all patients. In addition, the duodenobiliary reflux test was performed during
      the third month postoperatively. All patients were followed for 24 to 30 months.
      RESULTS: In group A, the SO basal and contraction pressures were 30.88+/-16.11
      and 77.46+/-23.62 mm Hg intraoperatively and 10.34+/-10.27 and 45.65+/-24.77 mm
      Hg 3 months postoperatively, respectively. In group B, the SO basal and
      contraction pressures were 27.80+/-15.88 and 73.96+/-23.99 mm Hg intraoperatively
      and 15.43+/-7.36 and 59.56+/-22.61 mm Hg 3 months postoperatively, respectively.
      During the third month postoperatively, duodenobiliary reflux was demonstrated in
      16 of 26 and 7 of 25 patients in groups A and B, respectively (P<0.05). During
      follow-up, the stone recurrence rates were 6 of 26 in group A and 1 of 25 in
      group B (P<0.05). CONCLUSIONS: After EST, the SO basal and contraction pressures
      decreased, and the duodenobiliary reflux and stone recurrence rates increased.
      Thus, EST should be selected with care.

PMID- 27031650
TI  - Long-term Survival Analysis of Robotic Versus Conventional Laparoscopic
      Hepatectomy for Hepatocellular Carcinoma: A Comparative Study.
AB  - PURPOSE: Robotic partial hepatectomy has been advocated as an alternative to
      conventional laparoscopic partial hepatectomy, but studies supporting the
      efficacy or oncological outcomes of robotic partial hepatectomy are scarce in the
      last decade. METHODS: This study compared the long-term oncological outcomes of
      robotic (n=100) and conventional laparoscopic hepatectomy (n=35) for
      hepatocellular carcinoma (HCC). RESULTS: Robotic group had a significant higher
      proportion of major hepatectomies (27% vs. 2.9%) and tumors located at or across
      posterosuperior segments (29% vs. 0%) than conventional laparoscopic group. For
      the perioperative outcomes, robotic group had a significant longer mean operation
      time (207.4 vs. 134.2 min). Both groups had similar blood loss (334.6 vs. 336
      mL). There was no difference in morbidity (14% vs. 20%) and mortality rate (0%
      vs. 0%). Concerning oncological outcomes, there was no difference between 2
      groups in R0 resection rate (96% vs. 91.4%), 5-year overall survival (65% vs.
      48%), and disease-free survival (42% vs. 38%). CONCLUSIONS: Robotic approach is
      an acceptable alternative to laparoscopic partial hepatectomy for HCC. With the
      potential advantages of robotic system in performing major hepatectomy and
      resection of tumor in difficult segments, robotic surgery may have an impact on
      the therapeutic strategy of HCC.

PMID- 27031651
TI  - Designing biomedical proteomics experiments: state-of-the-art and future
      perspectives.
AB  - With the current expanded technical capabilities to perform mass spectrometry
      based biomedical proteomics experiments, an improved focus on the design of
      experiments is crucial. As it is clear that ignoring the importance of a good
      design leads to an unprecedented rate of false discoveries which would poison our
      results, more and more tools are developed to help researchers designing
      proteomic experiments. In this review, we apply statistical thinking to go
      through the entire proteomics workflow for biomarker discovery and validation and
      relate the considerations that should be made at the level of hypothesis
      building, technology selection, experimental design and the optimization of the
      experimental parameters.

PMID- 27031652
TI  - Transition-Metal-Mediated Release of Nitric Oxide (NO) from S-Nitroso-N-acetyl-d
      penicillamine (SNAP): Potential Applications for Endogenous Release of NO at the
      Surface of Stents Via Corrosion Products.
AB  - Nitric oxide (NO), identified over the last several decades in many physiological
      processes and pathways as both a beneficial and detrimental signaling molecule,
      has been the subject of extensive research. Physiologically, NO is transported by
      a class of donors known as S-nitrosothiols. Both endogenous and synthetic S
      nitrosothiols have been reported to release NO during interactions with certain
      transition metals, primarily Cu(2+) and Fe(2+). Ag(+) and Hg(2+) have also been
      identified, although these metals are not abundantly present in physiological
      systems. Here, we evaluate Pt(2+), Fe(2+), Fe(3+), Mg(2+), Zn(2+), Mn(2+),
      Co(2+), Ni(2+), and Cu(2+) for their ability to generate NO from S-nitroso-N
      acetyl-d-penicillamine (SNAP) under physiological pH conditions. Specifically, we
      report NO generation from RSNOs initiated by three transition metal ions; Co(2+),
      Ni(2+), and Zn(2+), which have not been previously reported to generate NO.
      Additionally, preliminary in vivo evidence of zinc wires implanted in the rat
      arterial wall and circulating blood is presented which demonstrated inhibited
      thrombus formation after 6 months. One potentially useful application of these
      metal ions capable of generating NO from RSNOs is their use in the fabrication of
      biodegradable metallic stents capable of generating NO at the stent-blood
      interface, thereby reducing stent-related thrombosis and restenosis.

PMID- 27031654
TI  - Vaginal estrogen use and effects on quality of life and urogenital morbidity in
      postmenopausal women after publication of the Women's Health Initiative in New
      York City: Erratum.

PMID- 27031653
TI  - Comparison of nicotinamide adenine dinucleotide phosphate-induced immune
      responses against biotrophic and necrotrophic pathogens in Arabidopsis thaliana.
AB  - The pyridine nucleotide nicotinamide adenine dinucleotide phosphate (NADP) is a
      universal coenzyme in anabolic reactions and also functions in intracellular
      signaling by serving as a substrate for production of the Ca(2+)-mobilizing agent
      nicotinic acid adenine dinucleotide phosphate (NAADP). It has recently been shown
      that, in mammalian cells, cellular NADP can be released into the extracellular
      compartment (ECC) upon environmental stresses by active exocytosis or diffusion
      through transmembrane transporters in living cells or passive leakage across the
      membrane in dying cells. In the ECC, NADP can either serve as a substrate for
      production of NAADP or act directly on purinoceptors to activate transmembrane
      signaling. In the last several years, extracellular NADP has also been suggested
      to function in plant immune responses. Here, we compared exogenous NADP-induced
      immune responses against biotrophic and necrotrophic pathogens in the Arabidopsis
      thaliana ecotype Columbia and found that NADP addition induces salicylic acid
      mediated defense signaling but not jasmonic acid/ethylene-mediated defense
      responses. These results suggest the specificity of exogenous NADP-activated
      signaling in plants.

PMID- 27031655
TI  - TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL
      PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN
      WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN
      COLLEGE OF ENDOCRINOLOGY.
AB  - The American Association of Clinical Endocrinologists (AACE) and American College
      of Endocrinology (ACE) convened their first Workshop for recommendations to
      optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in
      diabetes (focusing on glycemic control), obesity (focusing on weight loss),
      thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on
      postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A
      standardized methodology is presented incorporating various transculturalization
      factors: resource availability (including imaging equipment and approved
      pharmaceuticals), health care professional and patient preferences, lifestyle
      variables, socio-economic parameters, web-based global accessibility, electronic
      implementation, and need for validation protocols. A standardized CPA template
      with node-specific recommendations to assist the local transculturalization
      process is provided. Participants unanimously agreed on the following five
      overarching principles for LA: (1) there is only one level of optimal endocrine
      care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3)
      nutrition education and increased pharmaceutical options are necessary to
      optimize the obesity care model, (4) quality neck ultrasound must be part of an
      optimal thyroid nodule care model, and (5) more scientific evidence is needed on
      osteoporosis prevalence and cost to justify intervention by governmental health
      care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured
      activity that assists local experts in creating culturally sensitive, evidence
      based, and easy-to-implement tools for optimizing endocrine care on a global
      scale.

PMID- 27031656
TI  - Exploring the Life Impact of Treated Low-Risk Thyroid Cancer.

PMID- 27031657
TI  - Correction.

PMID- 27031658
TI  - Cystic fibrosis: a model system for precision medicine.
AB  - PURPOSE OF REVIEW: Development of cystic fibrosis transmembrane conductance
      regulator (CFTR) modulators, small molecule therapies that target the basic
      defect in cystic fibrosis (CF), represents a new era in CF treatment. This review
      highlights recent progress in CF therapeutics as an example of precision medicine
      and personalized approaches to test CFTR modulators using preclinical model
      systems. RECENT FINDINGS: CFTR modulators are now clinically available for
      approximately 50% of the United States CF population. The CFTR potentiator,
      ivacaftor, is approved for people with CF ages 2 years and older with at least
      one gating mutation (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N,
      or S549R) or the R117H conductance mutation. The recent Food and Drug
      Administration approval of the corrector/potentiator combination,
      lumacaftor/ivacaftor, expands modulator therapy to people with CF homozygous for
      the F508del mutation, ages 12 years and older. Ivacaftor and lumacaftor, however,
      do not fully restore CFTR activity. Thus, next-generation correctors and
      potentiators are in development. Read-through agents targeting nonsense mutations
      and genotype agnostic treatments (gene-editing and gene therapy) are also in
      various phases of clinical development. SUMMARY: CFTR modulators promise to
      transform the therapeutic landscape in CF in a precision based fashion. Areas of
      ongoing research include developing drugs for all mutation classes so that all
      persons with CF can benefit from these therapies, and refining preclinical assays
      that allow the selection of the most effective treatments on an individual basis.

PMID- 27031659
TI  - Decontamination of the pediatric patient.
AB  - PURPOSE OF REVIEW: This article will review current guidelines for
      decontamination procedures for chemical, biological, and radiologic exposures
      with a focus on pediatric specific considerations. RECENT FINDINGS: There has
      been a global increase in terrorist incidents that expose large populations to
      toxic agents associated with significant morbidity and mortality. The
      pathophysiology, treatment, and management of these toxic exposures may be
      unfamiliar to the healthcare provider. Additionally, children are particularly
      vulnerable to terrorist threats as they have unique anatomical, physiological,
      psychological, and developmental characteristics distinct from the adult
      population. SUMMARY: Because pediatric patients are at greater risk than the
      general population, providers should be prepared to deliver age-appropriate care.
      Additionally, the ideal decontamination protocol is designed to maintain family
      units to maximize efficiency and minimize psychological trauma.

PMID- 27031660
TI  - Quality improvement in pediatric surgery.
AB  - PURPOSE OF REVIEW: The goal of this review is to provide updates on the evolution
      of conceptual definitions as they relate to quality in healthcare, existing
      measurement platforms for performance benchmarking in pediatric surgery, and
      available tools for quality improvement that are relevant to care of the
      pediatric surgical patient. RECENT FINDINGS: The American College of Surgeon's
      National Surgical Quality Improvement Program-Pediatric has continued to evolve,
      now providing risk-adjusted safety outcomes data to over 70 hospitals and
      broadening its scope of quality measurement to include resource utilization and
      value-based metrics. Increasing use of checklists and other team-based
      communication tools show potential for making surgical care safer for children,
      and thoughtful application of quality improvement methods such as Lean
      methodology, six-sigma and others are helping to improve efficiency and increase
      healthcare value. Finally, efforts to define minimal resource standards for
      pediatric surgical care holds promise to improve outcomes for neonates and other
      children with complex surgical needs. SUMMARY: Over the past decade, significant
      progress has been made in our ability to measure, benchmark and improve quality
      in pediatric surgery. Future efforts will need to facilitate broader
      participation in benchmarking programs and knowledge-sharing collaboratives, and
      to develop multidisciplinary, 'disease-specific' longitudinal care models where
      quality measurement extends before and beyond the 'traditional' 30-day
      perioperative period.

PMID- 27031661
TI  - Scratching the Surface of Suicide in Head and Neck Cancer.

PMID- 27031662
TI  - The effects of cytotoxic therapy in progressive IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is not always benign, and some patients at
      high risk of end-stage renal disease (ESRD) experience a rapid decline in renal
      function. This study retrospectively examined the beneficial effects of cytotoxic
      therapy. METHODS: We identified 102 patients with progressive IgAN despite
      optimal conservative management. Of these, 31 who received cytotoxic therapy and
      55 who were managed conservatively were included. RESULTS: Median eGFR and
      urinary protein-to-creatinine ratio (uPCR) at baseline did not differ between the
      groups (p = 0.475 and 0.259, respectively). Median GFR slope was also similar (p
      = 0.896). Cumulative renal survival was better in the cytotoxic therapy group
      than in the control group (p = 0.009). Cytotoxic therapy was associated with
      lower risk of progression to ESRD, independent of eGFR, uPCR, GFR slope and
      kidney histologic findings (HR 0.13, 95% CI 0.03-0.66). In the cytotoxic therapy
      group, the median GFR slope decreased from -7.8 (-10.5, -5.0) mL/min/1.73 m(2)
      per year to -3.4 (-5.1, -1.8) mL/min/1.73 m(2) per year after treatment (p <
      0.001). Mortality was not observed, but infection requiring hospitalization
      occurred at similar rates in both groups (p = 0.886). CONCLUSIONS: Cytotoxic
      therapy attenuated the rate of GFR decline and was associated with a favorable
      renal outcome in patients with progressive IgAN.

PMID- 27031663
TI  - Differential impact of visual feedback on plantar- and dorsi-flexion maximal
      torque output.
AB  - The effect of visual feedback on enhancing isometric maximal voluntary
      contractions (MVC) was evaluated. Twelve adults performed plantar-flexion and
      dorsi-flexion MVCs in 3 conditions (no visual feedback, visual feedback, and
      visual feedback with target). There was no significant effect of visual
      conditions on dorsi-flexion MVC but there was an effect on plantar-flexion.
      Irrespective of whether a target was evident, visual feedback increased plantar
      flexion MVC by ~15%. This study highlights the importance of optimal feedback to
      enhance MVC. 

PMID- 27031668
TI  - Targeted Therapy of Breast Cancer.

PMID- 27031669
TI  - From Discs to Ribbons Networks: The Second Critical Micelle Concentration in
      Nonionic Sterol Solutions.
AB  - At the critical micelle concentration (CMC), amphiphiles self-assemble into
      spherical micelles, typically followed by a transition at the second CMC to
      cylindrical micelles that are uniform in width but are polydispersed in length
      and have swollen ends. In this Letter, we report on a new structural path of self
      assembly that is based on discoidal (coin-like), rather than spherical, geometry;
      the nonionic sterol ChEO10 is shown to form monodisperse equilibrium disc
      assemblies at the first CMC, transitioning at the second CMC into flat ribbons
      that (like the cylindrical micelles) have uniform width, polydispersed length,
      and swollen ends. Increase in ChEO10 concentration or the temperature leads to
      ribbon elongation, branching, and network formation. This self-assembly path
      reveals that (1) surfactants can form equilibrium nonspherical assemblies at the
      CMC and (2) aggregate progression around the second CMC is similar for the disc
      and sphere geometries. 

PMID- 27031670
TI  - Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor
      Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction with High
      Cell Potency Identified by Fragment-Based Discovery.
AB  - KEAP1 is the key regulator of the NRF2-mediated cytoprotective response, and
      increasingly recognized as a target for diseases involving oxidative stress.
      Pharmacological intervention has focused on molecules that decrease NRF2
      ubiquitination through covalent modification of KEAP1 cysteine residues, but such
      electrophilic compounds lack selectivity and may be associated with off-target
      toxicity. We report here the first use of a fragment-based approach to directly
      target the KEAP1 Kelch-NRF2 interaction. X-ray crystallographic screening
      identified three distinct "hot-spots" for fragment binding within the NRF2
      binding pocket of KEAP1, allowing progression of a weak fragment hit to molecules
      with nanomolar affinity for KEAP1 while maintaining drug-like properties. This
      work resulted in a promising lead compound which exhibits tight and selective
      binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in
      vivo models, thereby providing a high quality chemical probe to explore the
      therapeutic potential of disrupting the KEAP1-NRF2 interaction.

PMID- 27031672
TI  - Errata.

PMID- 27031671
TI  - Enhancing the strain sensitivity of CoFe2O4 at low magnetic fields without
      affecting the magnetostriction coefficient by substitution of small amounts of Mg
      for Fe.
AB  - Attaining high magnetostrictive strain sensitivity (dlambda/dH) with high
      magnetostriction strain (lambda) is desirable for sintered polycrystalline cobalt
      ferrite for various applications. It is shown that substitution of a small amount
      of Fe(3+) by Mg(2+) in CoMgxFe2-xO4 (x < 0.1) gives a comparable maximum
      magnetostriction coefficient to that of the unsubstituted counterpart, with large
      improvement in the strain sensitivity at relatively low magnetic fields. A large
      increase in the magnetostriction coefficient is obtained at low magnetic fields
      for the substituted compositions. The magnetostriction parameters are further
      enhanced by magnetic field annealing of the sintered products. The results are
      analyzed based on powder XRD, Raman spectroscopy, XPS and magnetic measurements
      and based on the results from these studies, the changes in the magnetostriction
      parameters are correlated with the changes in the cation distribution, magnetic
      anisotropy and microstructure.

PMID- 27031673
TI  - Gelatin promotes murine fibrosarcoma L929 cell detachment and protects the cells
      from TNFalpha-induced cytotoxicity.
AB  - PURPOSE: Gelatin has been considered to exist as intermediate substance of
      collagen catabolism in tissue remodeling or under inflammatory conditions. We
      have initiated the study on possible biological functions of gelatin that can
      exist temporally and locally under the conditions of remodeling and inflammation
      Materials and methods: To this purpose, we investigated cell proliferation and
      survival on gelatin-coated dishes and the response to tumor necrosis factor alpha
      (TNFalpha)-induced cytotoxicity in L929 cells. Autophagy level, ATP level, and
      ROS generation are examined. RESULTS: L929 cells detached from the gelatin-coated
      dishes and formed multicellular aggregates. TNFalpha-induced cytotoxicity in L929
      cells was inhibited by gelatin-coating culture. The cells on gelatin-coated
      dishes showed reduced cellular ATP levels and increased adenosine 5'
      monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, leading to
      increased ROS generation and autophagy. CONCLUSION: This study showed that
      gelatin-coated culture protected L929 cells from TNFalpha-induced cytotoxicity
      and suggested for a possible pathophysiological function of gelatin in regulating
      cellular functions.

PMID- 27031674
TI  - Doctor, can I desensitize my food-allergic child using directly the allergenic
      molecules?
AB  - PURPOSE OF REVIEW: Food allergy has risen in prevalence worldwide and is one of
      the main causes of anaphylaxis, especially in children. The only possible
      therapeutic approach is specific immunotherapy. This review describes the recent
      approaches using allergenic molecules for specific immunotherapy. RECENT
      FINDINGS: Hypoallergenic tropomyosins from Metapenaeus ensis have been cloned and
      constructed by direct mutagenesis or epitope deletion and have been successfully
      used in shrimp-sensitized mice. A modified carp parvalbumin is being used in
      phase I/IIa clinical trials in patients with fish allergy. Natural lipid transfer
      protein (Pru p 3) and profilin (Pho d 2) extracts have been used for the
      treatment of patients with plant food allergy. Treatments of egg-sensitized mice
      with glycated-ovalbumin and ovomucoid peptides led to a clinical and
      immunological improvement. A preventive treatment with synthetic beta
      lactoglobulin peptides was effective in reducing skin symptoms in mice sensitized
      to milk whey proteins but no dominant epitopes were found in alpha-lactalbumin.
      Finally peanut desensitization has been attempted using three modified
      recombinant peanuts but the protocol was interrupted and limited to a phase 1
      study because of side-effects. SUMMARY: Many molecules, including allergenic
      peptides or modified proteins are under consideration but clinical trials in food
      allergic study participants are necessary to confirm tolerability and efficacy.

PMID- 27031675
TI  - Registries as useful tools in characterization of allergic manifestations.
AB  - PURPOSE OF REVIEW: Registries are useful to discover the applicability of data
      generated from randomized clinical trials (RCTs) into daily practice, and to
      search for real-life data usually not covered by them. RECENT FINDINGS: In
      allergy, registry research brought clues to important epidemiological and
      clinical problems hardly accessible with other methods. The increase in the
      asthma prevalence in Sweden in contrast with stabilization in Denmark; the
      association of the prevalence of asthma and environmental factors; the knowledge
      of existing rhinitis international guidelines, but the poorly complacence of some
      of their recommendations; the low epinephrine use in anaphylaxis and the
      difference among European and Latin American elicitors; the predominance of beta
      lactams or NSAIDs as drug hypersensitivity reactions inducers in different
      regions; the fact that most of the hereditary angioedema patients were receiving
      long-term prophylaxis with attenuated androgens; all the mentioned are clear
      examples of relevant and important data provided by current registries. SUMMARY:
      Registries in allergy enlighten knowledge in areas not covered by classical
      investigational methods. As the number and importance of registries is growing,
      its contribution to the knowledge and management of allergic diseases will
      increase in the near future.

PMID- 27031676
TI  - Cerebellar cathodal tDCS interferes with recalibration and spatial realignment
      during prism adaptation procedure in healthy subjects.
AB  - The aim of this study is to clarify the specific role of the cerebellum during
      prism adaptation procedure (PAP), considering its involvement in early prism
      exposure (i.e., in the recalibration process) and in post-exposure phase (i.e.,
      in the after-effect, related to spatial realignment). For this purpose we
      interfered with cerebellar activity by means of cathodal transcranial direct
      current stimulation (tDCS), while young healthy individuals were asked to perform
      a pointing task on a touch screen before, during and after wearing base-left
      prism glasses. The distance from the target dot in each trial (in terms of
      pixels) on horizontal and vertical axes was recorded and served as an index of
      accuracy. Results on horizontal axis, that was shifted by prism glasses, revealed
      that participants who received cathodal stimulation showed increased rightward
      deviation from the actual position of the target while wearing prisms and a
      larger leftward deviation from the target after prisms removal. Results on
      vertical axis, in which no shift was induced, revealed a general trend in the two
      groups to improve accuracy through the different phases of the task, and a trend,
      more visible in cathodal stimulated participants, to worsen accuracy from the
      first to the last movements in each phase. Data on horizontal axis allow to
      confirm that the cerebellum is involved in all stages of PAP, contributing to
      early strategic recalibration process, as well as to spatial realignment. On
      vertical axis, the improving performance across the different stages of the task
      and the worsening accuracy within each task phase can be ascribed, respectively,
      to a learning process and to the task-related fatigue.

PMID- 27031677
TI  - Nonverbal auditory working memory: Can music indicate the capacity?
AB  - Different working memory (WM) mechanisms that underlie words, tones, and timbres
      have been proposed in previous studies. In this regard, the present study
      developed a WM test with nonverbal sounds and compared it to the conventional
      verbal WM test. A total of twenty-five, non-music major, right-handed college
      students were presented with four different types of sounds (words, syllables,
      pitches, timbres) that varied from two to eight digits in length. Both accuracy
      and oxygenated hemoglobin (oxyHb) were measured. The results showed significant
      effects of number of targets on accuracy and sound type on oxyHb. A further
      analysis showed prefrontal asymmetry with pitch being processed by the right
      hemisphere (RH) and timbre by the left hemisphere (LH). These findings suggest a
      potential for employing musical sounds (i.e., pitch and timbre) as a
      complementary stimuli for conventional nonverbal WM tests, which can additionally
      examine its asymmetrical roles in the prefrontal regions.

PMID- 27031678
TI  - Systematic review of cases of cutaneous T-cell lymphoma transformation in
      pityriasis lichenoides and small plaque parapsoriasis.

PMID- 27031679
TI  - Colossal magnetoresistance in amino-functionalized graphene quantum dots at room
      temperature: manifestation of weak anti-localization and doorway to spintronics.
AB  - In this work, we have demonstrated the signatures of localized surface
      distortions and disorders in functionalized graphene quantum dots (fGQD) and
      consequences in magneto-transport under weak field regime (~1 Tesla) at room
      temperature. Observed positive colossal magnetoresistance (MR) and its
      suppression is primarily explained by weak anti-localization phenomenon where
      competitive valley (inter and intra) dependent scattering takes place at room
      temperature under low magnetic field; analogous to low mobility disordered
      graphene samples. Furthermore, using ab-initio analysis we show that sub-lattice
      sensitive spin-polarized ground state exists in the GQD as a result of pz orbital
      asymmetry in GQD carbon atoms with amino functional groups. This spin polarized
      ground state is believed to help the weak anti-localization dependent magneto
      transport by generating more disorder and strain in a GQD lattice under applied
      magnetic field and lays the premise for future graphene quantum dot based
      spintronic applications. 

PMID- 27031680
TI  - Risk factors associated with 30-day asthma readmissions.
AB  - OBJECTIVES: Assess factors that increase the odds of 30-day asthma readmissions
      to hospitals. METHODS: Retrospective chart review between 1/1/2002 to 12/31/2012
      of pediatric and adult patients with the primary diagnosis of asthma readmitted
      within 30 days after the index admission was performed. Patients were identified
      from billing database for asthma ICD 9 code (493.9). Inclusion criteria were:
      physician confirmed asthma diagnosis, one or more asthma admissions and
      accessible medical records. RESULTS: A total of 95 patients with multiple asthma
      readmissions were included in the final analysis. Thirty-seven patients (39%)
      were readmitted for asthma within 30 days and 58 patients (61%) had readmission
      in a 30-365-day period. Demographic characteristics were not significantly
      different between groups. Bivariate analysis showed that factors associated with
      higher likelihood of readmissions were a higher frequency of previous admissions,
      ED visits, inpatient hospitalizations, ICU stays, intubations, chest X-rays,
      history of chronic sinusitis, gastroesophageal reflux disease, anxiety, and the
      use of tiotropium or a long-acting beta-agonist (LABA). Multivariable analysis
      confirmed that prior hospital admissions and a history of GERD are the strongest
      predictive factors for early asthma readmissions, yet a history of environmental
      allergies might be a protective factor (p = 0.053). CONCLUSIONS: Non-allergic
      asthma patients with multiple prior admissions, ED visits and inpatient
      hospitalizations, on multiple medications with history of GERD, sinusitis, and
      anxiety are more likely to be readmitted within 30 days irrespective of other
      factors. Patients with these characteristics should be assessed for interventions
      in an effort to reduce early readmissions.

PMID- 27031681
TI  - Pseudofungal PAS-positive inclusion in the pericytes of cutaneous biopsies.

PMID- 27031682
TI  - Mechanistic insights into influenza vaccine-associated narcolepsy.
AB  - We previously reported an increased frequency of antibodies to hypocretin (HCRT)
      receptor 2 in sera obtained from narcoleptic patients who received the European
      AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the
      global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross
      reacted with a particular fragment of influenza nucleoprotein (NP) - one of the
      proteins naturally contained in the virus used to make seasonal influenza vaccine
      and pandemic influenza vaccines. The purpose of this commentary is to provide
      additional insights and interpretations of the findings and share additional data
      not presented in the original paper to help the reader appreciate the key
      messages of that publication. First, a brief background to narcolepsy and vaccine
      induced narcolepsy will be provided. Then, additional insights and clarification
      will be provided on the following topics: 1) the critical difference identified
      in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for
      the discordant association of narcolepsy between the AS03-adjuvanted pandemic
      vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the
      significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish
      control subjects, 4) the approach used for the detection of HCRTr2 antibodies in
      vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism
      involving HCRTr2 modulation in vaccine-associated narcolepsy.

PMID- 27031683
TI  - Self-Propelled and Long-Time Transport Motion of PVC Particles on a Water
      Surface.
AB  - Driven by the Marangoni effect, a poly(vinyl chloride) (PVC) particle runs in its
      orbit (a) with high velocity due to the release of surfactant and heat. The PVC
      particles are also able to efficiently drive an aluminum bulk and to induce
      spinning and quick runs on a water surface (b). 

PMID- 27031684
TI  - Implications of broadly neutralizing antibodies in the development of a universal
      influenza vaccine.
AB  - Serum antibodies are the major correlate of influenza vaccine efficacy, providing
      short-term protection against infection. Recent efforts have been focused on
      studying antibody responses at a monoclonal level to understand their role in
      protection against influenza, and to ultimately improve vaccine strategies to
      provide broader, long-term immunity against influenza virus. These studies have
      shown that broadly neutralizing antibodies specific for the conserved stem domain
      of the hemagglutinin protein can target multiple strains of influenza. These
      antibodies show great promise both from a therapeutic perspective as well as for
      guiding vaccine design efforts. In this review, we will summarize past and recent
      findings about broadly neutralizing antibodies against influenza, and discuss how
      these findings may guide development of universal vaccine strategies.

PMID- 27031685
TI  - Improving the effect of shear on skin viability with wound dressings.
AB  - BACKGROUND: Pressure ulcers are a major healthcare problem and caused by pressure
      and shear-forces. Although shear-force is understood to be a major contributing
      factor, no preventive interventions are specifically aimed at relieving the
      effect of shear on skin to improve skin viability. METHODS: A physical model was
      used to apply a combined loading of 2.4kPa pressure and 14.5N shear-force on skin
      in humans. Loading was applied on the volar aspect of both forearms for 30min in
      ten healthy volunteers. One arm received loading on skin with a wound dressing,
      the other arm (control) received loading directly on skin. The following
      parameters were determined before and after loading: IL-1alpha/Total Protein
      ratio (used as a measure of skin damage); Cutaneous blood cell flux ((CBF)
      measure of reactive hyperaemia); Lactate concentration (measure of tissue
      ischemia). Three different dressings were tested on three different days. The
      order of dressing application, dressing arm and start of the intervention were
      randomized. RESULTS: Participants mean age was 22.5+/-1.6 year with a BMI of
      22.3+/-2.4kg/m(2). IL-1alpha/Total Protein-ratio of the skin was significantly
      lower after the application of pressure and shear when the Mepilex(r) (P<0.01),
      Allevyn (P<0.05) or Aquacel(TM) dressing (P<0.01) was used compared with the
      control measurement. The Mepilex(r) dressing was more effective in reducing post
      load IL-1alpha/Total Protein-ratio compared to the Allevyn dressing (P<0.01).
      Post-load CBF was significantly lower when the Mepilex(r) or Aquacel dressing was
      used (P<0.001). Both dressings induced significantly less post-load CBF than the
      Allevyn dressing (P<0.01 and P<0.001, respectively). The concentration of lactate
      was not significantly increased after the application of pressure and shear and
      could not be used as a measure with this model. CONCLUSION: This is the first in
      vivo study to demonstrate that the effects of pressure in combination with shear
      on skin viability can be improved with foam dressings. In this study, the multi
      layered dressings perform better than the single-layered dressing.

PMID- 27031686
TI  - Artery buckling analysis using a two-layered wall model with collagen dispersion.
AB  - Artery buckling has been proposed as a possible cause for artery tortuosity
      associated with various vascular diseases. Since microstructure of arterial wall
      changes with aging and diseases, it is essential to establish the relationship
      between microscopic wall structure and artery buckling behavior. The objective of
      this study was to developed arterial buckling equations to incorporate the two
      layered wall structure with dispersed collagen fiber distribution. Seven porcine
      carotid arteries were tested for buckling to determine their critical buckling
      pressures at different axial stretch ratios. The mechanical properties of these
      intact arteries and their intima-media layer were determined via pressurized
      inflation test. Collagen alignment was measured from histological sections and
      modeled by a modified von-Mises distribution. Buckling equations were developed
      accordingly using microstructure-motivated strain energy function. Our results
      demonstrated that collagen fibers disperse around two mean orientations
      symmetrically to the circumferential direction (39.02 degrees +/-3.04 degrees )
      in the adventitia layer; while aligning closely in the circumferential direction
      (2.06 degrees +/-3.88 degrees ) in the media layer. The microstructure based two
      layered model with collagen fiber dispersion described the buckling behavior of
      arteries well with the model predicted critical pressures match well with the
      experimental measurement. Parametric studies showed that with increasing fiber
      dispersion parameter, the predicted critical buckling pressure increases. These
      results validate the microstructure-based model equations for artery buckling and
      set a base for further studies to predict the stability of arteries due to
      microstructural changes associated with vascular diseases and aging.

PMID- 27031688
TI  - Structural Studies of Trypanosoma brucei RNA Editing Ligases and Their Binding
      Partner Proteins.
AB  - To study the mechanism of ligating nicked RNA strands, we conducted molecular
      dynamics simulations of Trypanosoma brucei RNA editing ligases L1 and L2
      complexed with double-stranded RNA (dsRNA) fragments. In each resulting model, a
      Mg(2+) ion coordinates the 5'-PO4 of the nicked nucleotide and the 3'-OH of the
      terminal nucleotide for a nucleophilic reaction consistent with the postulated
      step 3 chemistry of the ligation mechanism. Moreover, coordination of the 3'-OH
      to the Mg(2+) ion may lower its pKa, thereby rendering it a more effective
      nucleophile as an oxyanion. Thus, Mg(2+) may play a twofold role: bringing the
      reactants into the proximity of each other and activating the nucleophile. We
      also conducted solvated interaction energy calculations to explore whether
      ligation specificities can be correlated to ligase-dsRNA binding affinity
      changes. The calculated dsRNA binding affinities are stronger for both L1 and L2
      when the terminal nucleotide is changed from cytosine to guanine, in line with
      their experimentally measured ligation specificities. Because the ligation
      mechanism is also influenced by interactions of the ligase with partner proteins
      from the editosome subcomplex, we also modeled the structure of the RNA-bound L2
      in complex with the oligonucleotide binding (OB) domain of largest editosome
      interacting protein A1. The resulting L2-dsRNA-A1 model, which is consistent with
      mutagenesis and binding data recorded to date, provides the first atomic-level
      glimpse of plausible interactions around the RNA ligation site in the presence of
      an OB domain presented in-trans to a nucleic acid ligase.

PMID- 27031689
TI  - Retail Deli Slicer Cleaning Frequency--Six Selected Sites, United States, 2012.
AB  - Listeria monocytogenes (Listeria) causes the third highest number of foodborne
      illness deaths (an estimated 255) in the United States annually, after
      nontyphoidal Salmonella species and Toxoplasma gondii (1). Deli meats are a major
      source of listeriosis illnesses, and meats sliced and packaged at retail delis
      are the major source of listeriosis illnesses attributed to deli meat (4).
      Mechanical slicers pose cross-contamination risks in delis and are an important
      source of Listeria cross-contamination. Reducing Listeria contamination of sliced
      meats in delis will likely reduce Listeria illnesses and outbreaks. Good slicer
      cleaning practices can reduce this foodborne illness risk. CDC's Environmental
      Health Specialists Network (EHS-Net) studied how often retail deli slicers were
      fully cleaned (disassembled, cleaned, and sanitized) at the Food and Drug
      Administration (FDA) Food Code-specified minimum frequency of every 4 hours and
      examined deli and staff characteristics related to slicer cleaning frequency.
      Interviews with staff members in 298 randomly-selected delis in six EHS-Net sites
      showed that approximately half of delis fully cleaned their slicers less often
      than FDA's specified minimum frequency. Chain-owned delis and delis with more
      customers, more slicers, required manager food safety training, food safety
      knowledgeable workers, written slicer-cleaning policies, and food safety
      certified managers fully cleaned their slicers more frequently than did other
      types of delis, according to deli managers or workers. States and localities
      should require deli manager training and certification, as specified in the FDA
      Food Code. They should also consider encouraging or requiring delis to have
      written slicer-cleaning policies. Retail food industry leaders can also implement
      these prevention efforts to reduce risk in their establishments. Because
      independent and smaller delis had lower frequencies of slicer cleaning,
      prevention efforts should focus on these types of delis.

PMID- 27031690
TI  - Molecular pathogenesis of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is an inherited iron overload disorder
      characterized by normal iron-driven erythropoiesis and abnormal iron metabolism,
      leading to excess iron deposited in parenchymal cells of liver, heart, and
      endocrine glands. Iron hormone, hepcidin, plays a critical role in iron
      homeostasis through interaction with ferroportin (FPN), a major cellular iron
      exporter. Hepcidin is encoded by hepcidin antimicrobial peptide (HAMP). Mutations
      in hepcidin and any genes that regulate the biology of hepcidin, including
      hemochromatosis genes (HFE), Hemojuvelin (HJV), transferring receptor 2 (TFR2)
      and FPN, result in hemochromatosis. The identification of hepcidin and its role
      will provide a better understanding for pathogenesis of HH. 

PMID- 27031691
TI  - Neopterin and Soluble CD14 Levels as Indicators of Immune Activation in Cases
      with Indeterminate Pattern and True Positive HIV-1 Infection.
AB  - BACKGROUND: We aimed to evaluate the roles of the plasma immune activation
      biomarkers neopterin and soluble CD14 (sCD14) in the indirect assessment of the
      immune activation status of patients with the indeterminate HIV-1 (IHIV-1)
      pattern and a true HIV-1-positive infection (PCG). METHODS: This cross-sectional
      and descriptive study included eighty-eight patients with the IHIV-1 pattern, 100
      patients in the PCG, and 100 people in a healthy control group (HCG). Neopterin
      and sCD14 levels were determined by competitive and sandwich ELISA methods,
      respectively. RESULTS: Mean neopterin and sCD14 levels among those with the IHIV
      1 pattern were significantly lower than among the PCG (p < 0.001 and p = 0.001,
      respectively), but they were similiar to those in the HCG (p = 0.57 and p = 0.66,
      respectively. Mean neopterin and sCD14 levels among the PCG were found to be
      significantly higher than among those with the IHIV-1 pattern (p < 0.001 and p =
      0.001, respectively) and among those in the HCG (p = 0.001, p < 0.001,
      respectively). Neopterin did not have adequate predictive value for identifying
      those in the PCG (area under the curve [AUC] = 0.534; 95% CI, 0.463-0.605; p =
      0.4256); sCD14 also had poor predictive value but high specificity (100%) for
      identifying those in the PCG (AUC = 0.627; 95% CI, 0.556-0.694; p = 0.0036).
      CONCLUSIONS: While low levels of these two biomarkers were detected among those
      with the IHIV-1 pattern, they were found in high levels among those in the PCG.
      These two markers obviously cannot be used as a sceening test because they have
      low sensitivies. Taken together, we suggest that neopterin and sCD14 may be
      helpful because they both have high specificity (92%-100%) as indirect non
      specific markers for predicting the immune activation status of individuals,
      whether or not they have true positive HIV-1.

PMID- 27031692
TI  - Microalbuminuria and the Combination of MRI Markers of Cerebral Small Vessel
      Disease.
AB  - BACKGROUND: Kidney function has been related to the presence of individual
      markers of cerebral small vessel disease (CSVD), as lacunes, white matter
      hyperintensities (WMH) or microbleeds. We aimed at studying the relationship of
      kidney dysfunction with the combination of several markers of CSVD. METHODS:
      Subjects are those included in the ISSYS cohort (Investigating Silent Strokes in
      hypertensives: a magnetic resonance imaging study). A scale ranging from 0 to 4
      points was applied based on the presence (one point each) of lacunes, deep
      microbleeds, moderate to extensive basal ganglia enlarged perivascular spaces
      (EPVS), and periventricular or deep WMH. We determined the creatinine-based
      glomerular filtration rate and the urinary albumin-to-creatinine ratio (UACR) as
      markers of kidney function and studied their association with the scale of CSVD
      in univariate and ordinal logistic regression analyses. RESULTS: Among the 975
      patients included, 28.2% presented one or more CSVD markers, being the most
      prevalent marker (either alone or in combination) basal ganglia EPVS. The UACR
      was elevated at increasing the scores of the CSVD scale and remained as
      independent predictor of the combination of markers (common OR per natural log
      unit increase in UACR: 1.23, 1.07-1.41) after controlling per age, gender,
      cardiovascular risk, antihypertensive treatment and hypertension duration. In
      contrast, no associations were found between the CSVD scores and the creatinine
      based estimated glomerular filtration rate. CONCLUSIONS: A significant proportion
      of stroke-free hypertensives present at least one imaging marker of CSVD. UACR
      but not creatinine-based glomerular filtration rate is associated with the
      combination of markers of CSVD.

PMID- 27031693
TI  - Remotely Sensed High-Resolution Global Cloud Dynamics for Predicting Ecosystem
      and Biodiversity Distributions.
AB  - Cloud cover can influence numerous important ecological processes, including
      reproduction, growth, survival, and behavior, yet our assessment of its
      importance at the appropriate spatial scales has remained remarkably limited. If
      captured over a large extent yet at sufficiently fine spatial grain, cloud cover
      dynamics may provide key information for delineating a variety of habitat types
      and predicting species distributions. Here, we develop new near-global, fine
      grain (~1 km) monthly cloud frequencies from 15 y of twice-daily Moderate
      Resolution Imaging Spectroradiometer (MODIS) satellite images that expose
      spatiotemporal cloud cover dynamics of previously undocumented global complexity.
      We demonstrate that cloud cover varies strongly in its geographic heterogeneity
      and that the direct, observation-based nature of cloud-derived metrics can
      improve predictions of habitats, ecosystem, and species distributions with
      reduced spatial autocorrelation compared to commonly used interpolated climate
      data. These findings support the fundamental role of remote sensing as an
      effective lens through which to understand and globally monitor the fine-grain
      spatial variability of key biodiversity and ecosystem properties. 

PMID- 27031694
TI  - Design and Implementation of an Interactive Web-Based Near Real-Time Forest
      Monitoring System.
AB  - This paper describes an interactive web-based near real-time (NRT) forest
      monitoring system using four levels of geographic information services: 1) the
      acquisition of continuous data streams from satellite and community-based
      monitoring using mobile devices, 2) NRT forest disturbance detection based on
      satellite time-series, 3) presentation of forest disturbance data through a web
      based application and social media and 4) interaction of the satellite based
      disturbance alerts with the end-user communities to enhance the collection of
      ground data. The system is developed using open source technologies and has been
      implemented together with local experts in the UNESCO Kafa Biosphere Reserve,
      Ethiopia. The results show that the system is able to provide easy access to
      information on forest change and considerably improves the collection and storage
      of ground observation by local experts. Social media leads to higher levels of
      user interaction and noticeably improves communication among stakeholders.
      Finally, an evaluation of the system confirms the usability of the system in
      Ethiopia. The implemented system can provide a foundation for an operational
      forest monitoring system at the national level for REDD+ MRV applications. 

PMID- 27031695
TI  - Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting
      MAPKs and Apoptosis.
AB  - Despite its broad applications, cisplatin affords considerable nephro- and
      hepatotoxicity through triggering inflammatory and oxidative stress cascades. The
      aim of the current investigation was to study the possible protective effects of
      tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on
      cisplatin-evoked hepatic dysfunction and histopathologic changes along with
      oxidative stress, inflammatory and apoptotic biomarkers were investigated
      compared to silymarin. Tangeretin pre-treatment significantly improved liver
      function tests (ALT and AST), inhibited cisplatin-induced lipid profile
      aberrations (total cholesterol and triglycerides) and diminished histopathologic
      structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced
      hepatic inflammatory events as indicated by suppression of tumor necrosis factor
      alpha (TNF-alpha) and enhancement of interleukin-10 (IL-10). Meanwhile, it
      lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2
      related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and
      glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK)
      pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho
      c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase
      (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression
      with augmentation of Bcl-2 promoting liver cell survival. Our results highlight
      the protective effects of tangeretin against cisplatin-induced acute hepatic
      injury via the concerted modulation of inflammation, oxidative stress, MAPKs and
      apoptotic pathways. 

PMID- 27031696
TI  - Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site
      and Involved Proteases.
AB  - RATIONALE: ABCA3 is a lipid transporter in the limiting membrane of lamellar
      bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory
      distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is
      N-terminally cleaved by an as yet unknown protease, a process believed to
      regulate ABCA3 activity. METHODS: The exact site where ABCA3 is cleaved was
      localized using mass spectrometry (MS). Proteases involved in ABCA3 processing
      were identified using small molecule inhibitors and siRNA mediated gene
      knockdown. Results were verified by in vitro digestion of a synthetic peptide
      substrate mimicking ABCA3's cleavage region, followed by MS analysis. RESULTS: We
      found that cleavage of ABCA3 occurs after Lys174 which is located in the
      proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent,
      cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed
      activity against the ABCA3 peptide in vitro with cathepsin L being more active.
      CONCLUSION: We show here that, like some other proteins of the lysosomal
      membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may
      represent a potential target to therapeutically influence ABCA3 activity in ABCA3
      associated lung disease.

PMID- 27031697
TI  - Carbon and Nitrogen Mineralization in Relation to Soil Particle-Size Fractions
      after 32 Years of Chemical and Manure Application in a Continuous Maize Cropping
      System.
AB  - Long-term manure application is recognized as an efficient management practice to
      enhance soil organic carbon (SOC) accumulation and nitrogen (N) mineralization
      capacity. A field study was established in 1979 to understand the impact of long
      term manure and/or chemical fertilizer application on soil fertility in a
      continuous maize cropping system. Soil samples were collected from field plots in
      2012 from 9 fertilization treatments (M0CK, M0N, M0NPK, M30CK, M30N, M30NPK,
      M60CK, M60N, and M60NPK) where M0, M30, and M60 refer to manure applied at rates
      of 0, 30, and 60 t ha(-1) yr(-1), respectively; CK indicates no fertilizer; N and
      NPK refer to chemical fertilizer in the forms of either N or N plus phosphorus
      (P) and potassium (K). Soils were separated into three particle-size fractions
      (2000-250, 250-53, and <53 MUm) by dry- and wet-sieving. A laboratory incubation
      study of these separated particle-size fractions was used to evaluate the effect
      of long-term manure, in combination with/without chemical fertilization
      application, on the accumulation and mineralization of SOC and total N in each
      fraction. Results showed that long-term manure application significantly
      increased SOC and total N content and enhanced C and N mineralization in the
      three particle-size fractions. The content of SOC and total N followed the order
      2000-250 MUm > 250-53 MUm > 53 MUm fraction, whereas the amount of C and N
      mineralization followed the reverse order. In the <53 MUm fraction, the M60NPK
      treatment significantly increased the amount of C and N mineralized (7.0 and 10.1
      times, respectively) compared to the M0CK treatment. Long-term manure
      application, especially when combined with chemical fertilizers, resulted in
      increased soil microbial biomass C and N, and a decreased microbial metabolic
      quotient. Consequently, long-term manure fertilization was beneficial to both
      soil C and N turnover and microbial activity, and had significant effect on the
      microbial metabolic quotient.

PMID- 27031699
TI  - The Unifying Nature of Basic Science Research.

PMID- 27031698
TI  - Critical Endothelial Regulation by LRP5 during Retinal Vascular Development.
AB  - Vascular abnormalities in the eye are the leading cause of many forms of
      inherited and acquired human blindness. Loss-of-function mutations in the Wnt
      binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of
      vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The
      canonical Wnt-beta-catenin pathway is known to regulate retinal vascular
      development. However, it is unclear what precise role LPR5 plays in this process.
      Here, we show that loss of LRP5 function in mice causes retinal
      hypovascularization during development as well as retinal neovascularization in
      adulthood with disorganized and leaky vessels. Using a highly specific Flk1
      CreBreier line for vascular endothelial cells, together with several genetic
      models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the
      retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function
      only in endothelial cells in Lrp5-/- mice rescues their retinal vascular
      abnormalities. Furthermore, we show that retinal vascularization is regulated by
      LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides
      the first direct evidence that endothelium-derived LRP5 is both necessary and
      sufficient to mediate its critical role in the development and maintenance of
      retinal vasculature. 

PMID- 27031700
TI  - Rural Doctors' Views on and Experiences with Evidence-Based Medicine: The FrEEDoM
      Qualitative Study.
AB  - BACKGROUND: Evidence-based medicine is the integration of individual clinical
      expertise, best external evidence and patient values which was introduced more
      than two decades ago. Yet, primary care physicians in Malaysia face unique
      barriers in accessing scientific literature and applying it to their clinical
      practice. AIM: This study aimed to explore the views and experiences of rural
      doctors' about evidence-based medicine in their daily clinical practice in a
      rural primary care setting. METHODS: Qualitative methodology was used. The
      interviews were conducted in June 2013 in two rural health clinics in Malaysia.
      The participants were recruited using purposive sampling. Four focus group
      discussions with 15 medical officers and three individual in-depth interviews
      with family medicine specialists were carried out. All interviews were conducted
      using a topic guide and were audio-recorded, transcribed verbatim, checked and
      analyzed using a thematic approach. RESULTS: Key themes identified were: (1)
      doctors viewed evidence-based medicine mainly as statistics, research and
      guidelines, (2) reactions to evidence-based medicine were largely negative, (3)
      doctors relied on specialists, peers, guidelines and non-evidence based internet
      sources for information, (4) information sources were accessed using novel
      methods such as mobile applications and (5) there are several barriers to
      evidence-based practice, including doctor-, evidence-based medicine-, patient-
      and system-related factors. These included inadequacies in knowledge, attitude,
      management support, time and access to evidence-based information sources.
      Participants recommended the use of online services to support evidence-based
      practice in the rural settings. CONCLUSION: The level of evidence-based practice
      is low in the rural setting due to poor awareness, knowledge, attitude and
      resources. Doctors use non-evidence based sources and access them through new
      methods such as messaging applications. Further research is recommended to
      develop and evaluate interventions to overcome the identified barriers.

PMID- 27031701
TI  - Expression and Localization of Opioid Receptors in Male Germ Cells and the
      Implication for Mouse Spermatogenesis.
AB  - The presence of endogenous opioid peptides in different testicular cell types has
      been extensively characterized and provides evidence for the participation of the
      opioid system in the regulation of testicular function. However, the exact role
      of the opioid system during the spermatogenesis has remained controversial since
      the presence of the mu-, delta- and kappa-opioid receptors in spermatogenic cells
      was yet to be demonstrated. Through a combination of quantitative real-time PCR,
      immunofluorescence, immunohistochemistry and flow cytometry approaches, we report
      for the first time the presence of active mu-, delta- and kappa-opioid receptors
      in mouse male germ cells. They show an exposition time-dependent response to
      opioid agonist, hence suggesting their active involvement in spermatogenesis. Our
      results contribute to understanding the role of the opioid receptors in the
      spermatogenesis and could help to develop new strategies to employ the opioid
      system as a biochemical tool for the diagnosis and treatment of male infertility.

PMID- 27031702
TI  - Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial
      Virus Infection in Pregnancy.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of
      viral pneumonia in children worldwide. A maternal vaccine may protect both the
      mother and infant from RSV illness. The epidemiology and clinical presentation of
      RSV in pregnant and postpartum women is not well-described. METHODS: Data were
      collected from a prospective, randomized trial of influenza immunization in
      pregnant women in rural southern Nepal. Women were enrolled in their second
      trimester of pregnancy and followed until six months postpartum. Active weekly
      home-based surveillance for febrile respiratory illness was performed. Mid-nasal
      swabs collected with episodes of respiratory illness were tested for RSV by real
      time polymerase chain reaction. RESULTS: RSV was detected in 14 (0.4%) illness
      episodes in 3693 women over 3554 person-years of surveillance from 2011-2014. RSV
      incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between
      September and December. Seven (50%) women sought care for RSV illness; none died.
      Of the 7 (50%) illness episodes during pregnancy, all had live births with 2
      (29%) preterm births and a median birthweight of 3060 grams. This compares to 469
      (13%) preterm births and a median birthweight of 2790 grams in women without RSV
      during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was
      detected in 4 (57%) of their infants. CONCLUSIONS: RSV was an uncommon cause of
      febrile respiratory illness in mothers during pregnancy in Nepal. These data will
      inform prevention and therapeutic strategies against RSV in resource-limited
      settings.

PMID- 27031703
TI  - Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome.
AB  - Although cryopreservation has been developed and optimized over the past decades,
      it causes various stresses, including cold shock, osmotic stress, and ice crystal
      formation, thereby reducing fertility. During cryopreservation, addition of
      cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing
      damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause
      damage to spermatozoa. To identify the effects of CPA addition during
      cryopreservation, we assessed the motility (%), motion kinematics, capacitation
      status, and viability of epididymal spermatozoa using computer-assisted sperm
      analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the
      effects of CPA addition were also demonstrated at the proteome level using two
      dimensional electrophoresis. Our results demonstrated that CPA addition
      significantly reduced sperm motility (%), curvilinear velocity, viability (%),
      and non-capacitated spermatozoa, whereas straightness and acrosome-reacted
      spermatozoa increased significantly (p < 0.05). Ten proteins were differentially
      expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA,
      whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta,
      superoxide dismutase 2, and outer dense fiber protein 2 were associated with
      several important signaling pathways (p < 0.05). The present study provides a
      mechanistic basis for specific cryostresses and potential markers of CPA-induced
      stress. Therefore, these might provide information about the development of safe
      biomaterials for cryopreservation and basic ground for sperm cryopreservation. 

PMID- 27031704
TI  - Limited amplification of chronic wasting disease prions in the peripheral tissues
      of intracerebrally inoculated cattle.
AB  - Chronic wasting disease (CWD) is a fatal neurodegenerative disease, classified as
      a prion disease or transmissible spongiform encephalopathy (TSE) similar to
      bovine spongiform encephalopathy (BSE). Cervids affected by CWD accumulate an
      abnormal protease-resistant prion protein throughout the central nervous system
      (CNS), as well as in both lymphatic and excretory tissues - an aspect of prion
      disease pathogenesis not observed in cattle with BSE. Using seeded amplification
      through real-time quaking-induced conversion, we investigated whether the bovine
      host or prion agent was responsible for this aspect of TSE pathogenesis. We
      blindly examined numerous central and peripheral tissues from cattle inoculated
      with CWD for prion seeding activity. Seeded amplification was readily detected in
      the CNS, though rarely observed in peripheral tissues, with a limited
      distribution similar to that of BSE prions in cattle. This seems to indicate that
      prion peripheralization in cattle is a host-driven characteristic of TSE
      infection.

PMID- 27031705
TI  - Klebsiella alba is a later heterotypic synonym of Klebsiella quasipneumoniae
      subsp. similipneumoniae.
AB  - The taxonomic position of Klebsiella alba was re-examined. The reconstructed
      phylogenetic tree based on multilocus sequence analysis showed that Klebsiella
      alba LMG 24441T (=KCTC 12878T) was closely related to Klebsiella quasipneumoniae
      subsp. similipneumoniae 07A044T, showing 99.5-100 % similarities for fusA, gapA,
      gyrA, leuS, pyrG, rpoB, rpoB2, atpD, gyrB and infB gene sequences and
      concatenated partial fusA, gapA, gyrA, leuS, pyrG, rpoB2, atpD, gyrB and infB
      gene sequences. High sequence similarities between Klebsiella alba LMG 24441T and
      Klebsiella quasipneumoniae subsp. similipneumoniae 07A044T indicated that they
      have the same taxonomic position. Klebsiellaalba was reclassified as
      Klebsiellaquasipneumoniae subsp. similipneumoniae and Klebsiella alba is a later
      heterotypic synonym of Klebsiella quasipneumoniae subsp. similipneumoniae. 

PMID- 27031706
TI  - Diagnostic accuracy of a mathematical model to predict apnea-hypopnea index using
      nighttime pulse oximetry.
AB  - The intent of this study is to develop a predictive model to convert an oxygen
      desaturation index (ODI) to an apnea-hypopnea index (AHI). This model will then
      be compared to actual AHI to determine its precision. One thousand four hundred
      and sixty-seven subjects given polysomnograms with concurrent pulse oximetry
      between April 14, 2010, and February 7, 2012, were divided into model development
      (n = 733) and verification groups (n = 734) in order to develop a predictive
      model of AHI using ODI. Quadratic regression was used for model development. The
      coefficient of determination (r(2)) between the actual AHI and the predicted AHI
      (PredAHI) was 0.80 (r = 0.90), which was significant at a p < 0.001. The areas
      under the receiver operating characteristic curve ranged from 0.96 for AHI
      thresholds of >= 10 and >= 15/h to 0.97 for thresholds of >= 5 and >= 30/h. The
      algorithm described in this paper provides a convenient and accurate way to
      convert ODI to a predicted AHI. This tool makes it easier for clinicians to
      understand oximetry data in the context of traditional measures of sleep apnea.

PMID- 27031707
TI  - Statistically Controlling for Confounding Constructs Is Harder than You Think.
AB  - Social scientists often seek to demonstrate that a construct has incremental
      validity over and above other related constructs. However, these claims are
      typically supported by measurement-level models that fail to consider the effects
      of measurement (un)reliability. We use intuitive examples, Monte Carlo
      simulations, and a novel analytical framework to demonstrate that common
      strategies for establishing incremental construct validity using multiple
      regression analysis exhibit extremely high Type I error rates under parameter
      regimes common in many psychological domains. Counterintuitively, we find that
      error rates are highest--in some cases approaching 100%--when sample sizes are
      large and reliability is moderate. Our findings suggest that a potentially large
      proportion of incremental validity claims made in the literature are spurious. We
      present a web application (http://jakewestfall.org/ivy/) that readers can use to
      explore the statistical properties of these and other incremental validity
      arguments. We conclude by reviewing SEM-based statistical approaches that
      appropriately control the Type I error rate when attempting to establish
      incremental validity.

PMID- 27031708
TI  - The Influence of Texting Language on Grammar and Executive Functions in Primary
      School Children.
AB  - When sending text messages on their mobile phone to friends, children often use a
      special type of register, which is called textese. This register allows the
      omission of words and the use of textisms: instances of non-standard written
      language such as 4ever (forever). Previous studies have shown that textese has a
      positive effect on children's literacy abilities. In addition, it is possible
      that children's grammar system is affected by textese as well, as grammar rules
      are often transgressed in this register. Therefore, the main aim of this study
      was to investigate whether the use of textese influences children's grammar
      performance, and whether this effect is specific to grammar or language in
      general. Additionally, studies have not yet investigated the influence of textese
      on children's cognitive abilities. Consequently, the secondary aim of this study
      was to find out whether textese affects children's executive functions. To
      investigate this, 55 children between 10 and 13 years old were tested on a
      receptive vocabulary and grammar performance (sentence repetition) task and
      various tasks measuring executive functioning. In addition, text messages were
      elicited and the number of omissions and textisms in children's messages were
      calculated. Regression analyses showed that omissions were a significant
      predictor of children's grammar performance after various other variables were
      controlled for: the more words children omitted in their text messages, the
      better their performance on the grammar task. Although textisms correlated
      (marginally) significantly with vocabulary, grammar and selective attention
      scores and omissions marginally significantly with vocabulary scores, no other
      significant effects were obtained for measures of textese in the regression
      analyses: neither for the language outcomes, nor for the executive function
      tasks. Hence, our results show that textese is positively related to children's
      grammar performance. On the other hand, use of textese does not affect-
      positively nor negatively--children's executive functions.

PMID- 27031709
TI  - Correction: Potential Cost-Effectiveness of Prenatal Distribution of Misoprostol
      for Prevention of Postpartum Hemorrhage in Uganda.

PMID- 27031711
TI  - Ribonucleases. Possible new approach in cancer therapy.
AB  - In the review, the use of the ribonucleases for cancer therapy is discussed.
      Using of epigenetic mechanisms of regulation--blocking protein synthesis without
      affecting the DNA structure--is a promising direction in the therapy. The
      ribonucleases isolated from different sources, despite of similar mechanism of
      enzymatic reactions, have different biological effects. The use of enzymes
      isolated from new sources, particularly from plants and fungi, shows promising
      results. In this article we discuss the new approach for the use of enzymes
      resistant to inhibitors and ribozymes, that is aimed at the destruction of the
      oncogene specific mRNA and the induction of apoptosis.

PMID- 27031710
TI  - Beneficial Effect of Moderate Exercise in Kidney of Rat after Chronic Consumption
      of Cola Drinks.
AB  - AIM: The purpose of this study was to investigate the effect of moderate
      intensity exercise on kidney in an animal model of high consumption of cola soft
      drinks. METHODS: Forty-eight Wistar Kyoto rats (age: 16 weeks; weight: 350-400 g)
      were assigned to the following groups: WR (water runners) drank water and
      submitted to aerobic exercise; CR (cola runners) drank cola and submitted to
      aerobic exercise; WS (water sedentary) and CS (cola sedentary), not exercised
      groups. The aerobic exercise was performed for 5 days per week throughout the
      study (24 weeks) and the exercise intensity was gradually increased during the
      first 8 weeks until it reached 20 meters / minute for 30 minutes. Body weight,
      lipid profile, glycemia, plasma creatinine levels, atherogenic index of plasma
      (AIP) and systolic blood pressure (SBP) were determined. After 6 months all rats
      were sacrificed. A kidney histopathological score was obtained using a
      semiquantitative scale. Glomerular size and glomerulosclerosis were estimated by
      point-counting. The oxidative stress and pro-inflammatory status were explored by
      immunohistochemistry. A one way analysis of variance (ANOVA) with Tukey-Kramer
      post-hoc test or the Kruskal-Wallis test with Dunn's post-hoc test was used for
      statistics. A value of p < 0.05 was considered significant. RESULTS: At 6 months,
      an increased consumption of cola soft drink was shown in CS and CR compared with
      water consumers (p<0.0001). Chronic cola consumption was associated with
      increased plasma triglycerides, AIP, heart rate, histopathological score,
      glomerulosclerosis, oxidative stress and pro-inflammatory status. On the other
      hand, moderate exercise prevented these findings. No difference was observed in
      the body weight, SBP, glycemia, cholesterol and plasma creatinine levels across
      experimental groups. CONCLUSIONS: This study warns about the consequences of
      chronic consumption of cola drinks on lipid metabolism, especially regarding
      renal health. Additionally, these findings emphasize the protective role of
      exercise training on renal damage.

PMID- 27031712
TI  - HIF-1--a big chapter in the cancer tale.
AB  - Approximately 1.0-1.5% of the genome is transcriptionally regulated by hypoxia,
      and hypoxia-inducible factor (HIF)-1alpha is the transcription factor modulating
      many of these genes. Cancer cells are able to survive hypoxic environments and
      hypoxia itself can activate adaptive cellular responses that contribute to tumor
      progression. Many HIF-1alpha-mediated biological effects are beneficial for tumor
      progression, including metabolic shift toward glycolysis, inhibition of fatty
      acid beta-oxidation, production of cellular reactive oxygen species and altering
      expression of tumor suppressor genes. HIF-1 promotes selective mitochondrial
      autophagy, resistance to T cell mediated lysis of cancer cells, induction of
      pluripotent cancer stem cells, epithelial-mesenchymal and epithelial-mesenchymal
      endothelial transitions beneficial for tumor growth and progression, loss of E
      cadherin. HIF-1 also induces production of signal molecules and cytokines by
      carcinoma-associated fibroblasts and upregulation of certain microRNAs important
      for cancer progression. This minireview focuses on the HIF-1 promoting role in
      tumor initiation and progression and HIF-1 targeting. HIF-1 pathway
      downregulation seems to be promising in future cancer treatment. 

PMID- 27031713
TI  - Inhibition of malignant potential and expression of proteins associated with
      epithelial-mesenchymal transition in Lewis lung carcinoma cells transduced with
      murine ifn-beta gene in recombinant baculovirus.
AB  - AIM: To analyze biological characteristics, malignant potential and expression of
      proteins associated with epithelial-mesenchymal transition in murine lung
      carcinoma cells transduced with interferon-beta (ifn-beta) gene in baculovirus
      vector. MATERIALS AND METHODS: The study was performed on Lewis lung carcinoma
      (LL) cells transduced with ifn-beta gene in recombinant baculovirus vector.
      Biological characteristics of the LL cells were studied with the use of standard
      cell culture methods, cytogenetic and immunocytochemical assays. RESULTS:
      Recombinant baculovirus-mediated transduction of LL cells with ifn-beta gene
      resulted in significant decrease of cell growth rate and density both in complete
      and serum-free medium. Also, LL cells transduction with ifn-beta gene
      significantly inhibited cell migration in vitro. Transduction of LL cells by
      baculovirus vector with or without ifn-beta gene caused significant genotoxic
      effect in these cells. Furthermore, ifn-beta gene transfer to lung carcinoma
      cells resulted in significant increase of nuclear expression of p19(ARF) (p <
      0.01), p21(WAF1) (p < 0.01), cytoplasmic expression of E-cadherin (p < 0.005) and
      inhibition of transcription factors of epithelial-mesenchymal transition (EMT)
      Twist (p < 0.005) and Slug (p < 0.01) expression. CONCLUSIONS: Transduction with
      ifn-beta gene of LL cells in recombinant baculovirus resulted in acquirement of
      less malignant phenotype in vitro and suppressed expression of proteins
      associated with EMT.

PMID- 27031714
TI  - CD40/CD40 ligand interactions and TNFalpha treatment reduce activity of P105
      promoter of the human papilloma virus-18 in vitro.
AB  - BACKGROUND: Cervical carcinoma cells including those infected with the oncogenic
      human papilloma virus (HPV) and several cervical carcinoma cell lines show a
      strong expression of the CD40 receptor, unlike benign cervical epithelial cells
      infected with HPV. The functional relevance of this up-regulated expression in
      the tumor is not fully understood. Nevertheless, it might offer a unique
      possibility to target those malignant cells due to the antiviral and antitumoral
      effects of the CD40/CD40 ligand (CD40L) interactions. AIM: In vitro assessment of
      the effect of CD40L on HPV 18-P105 promoter activity and the subsequent release
      of IL-6 by the promoter transfected HeLa(CD40) cells, which express CD40
      constitutively. MATERIAL AND METHODS: Transfection of HeLa(CD40) cells was
      achieved by electroporation after optimizing the parameters by the pCMV-beta-Gal
      vector and beta-Gal stain. Transfected HeLa(CD40) cells were challenged with
      BHK(CD40L) and TNFalpha, in addition to BHK(wt) and medium alone as controls.
      HPV18-P105 promoter activity was demonstrated by luciferase reporter gene assay
      while IL-6 was assessed by ELISA. RESULTS: CD40/CD40L interactions and TNFalpha
      treatment significantly reduced HPV18-P105 promoter activity (56.0 +/- 10.2% and
      64.1 +/- 9.1% vs. control, respectively; p < 0.001). Likewise, IL-6, which is a
      sensitive cytokine of CD40 activation, was significantly increased in HeLa(CD40)
      cells in the same experiments (2.7 fold after stimulation with BHK(CD40L) and 5.2
      fold after stimulation with TNFalpha vs. control; p < 0.01 and p < 0.001,
      respectively). CONCLUSION: It is likely that the CD40/CD40L interactions and
      TNFalpha are effective against cervical carcinomas by repressing transcriptional
      activity of HPV promoter. This can result in new adjuvant treatments.

PMID- 27031715
TI  - Effect of 5-azacytidine on miRNA expression in human breast cancer cells with
      different sensitivity to cytostatics.
AB  - AIM: To analyze expression of miRNA in human breast cancer cells, sensitive and
      resistant to cisplatin and doxorubicin, and to explore possible modification of
      drug sensitivity via treatment of cells with 5-azacytidine (5-aza), a
      demethylating agent. MATERIALS AND METHODS: The study was performed on wild-type
      MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant
      to doxorubicin and cisplatin, respectively. Cells were treated with 5-aza,
      cisplatin, doxorubicin and their combinations. Relative expression levels of
      miRNA-221, -200b, -320a, -10b, -34a, -122 and -29b were examined, using qRT-PCR.
      The MTT assay was used to monitor cell viability. RESULTS: We compared miRNA
      expression profiles in MCF-7/S and drug resistant MCF-7/Dox and MCF-7/DDP cells.
      Changes of miRNA-221, -200b, -320a, -10b, -34a, -122 and -29b were observed in
      both resistant cell lines. The most significant differences were found for miRNA
      200b (decreased in 50.0 +/- 2.6 and 63.0 +/- 3.1 times for MCF-7/Dox and MCF
      7/DDP cells, respectively) and for oncogenic miRNA-221 levels (increase in 62.0
      +/- 5.7 times for MCF-7/Dox and 83.8 +/- 7.2 times for MCF-7/DDP cells). 5-aza
      treatment caused an increase of miRNA-10b, -122, -200b levels in MCF-7/S cells,
      miRNA-34a, -10b, -122, -200b and -320a levels in MCF-7/Dox cells and miRNA-34a, 
      10b, -200b and -320a levels in MCF-7/DDP cells. Pretreatment of all studied lines
      with 5-aza resulted in the increase of their sensitivity to studied cytostatics.
      In particular, the IC50 of doxorubicin decreased by 2-, 4- and 3-fold for cell
      lines MCF-7/S, MCF-7/Dox and MCF-7/DDP cells, respectively, and IC50 of cisplatin
      in studied cultures decreased by 3-, 2- and 1.5-fold, respectively. CONCLUSIONS:
      It was shown that use of 5-aza can modify sensitivity of breast cancer cells to
      cytotoxic drugs not only by it's demetylation effect, but also by changes in
      expression of miRNAs, involved in cell proliferation, migration and drug
      resistance development.

PMID- 27031716
TI  - Superoxide- and NO-dependent mechanisms of antitumor and antimetastatic effect of
      L-arginine hydrochloride and coenzyme Q10.
AB  - AIM: To study the redox-dependent mechanism of antiradical, antitumor and
      antimetastatic action of L-arginine hydrochloride (L-Arg) and coenzyme Q10
      (CoQ10) in vivo. MATERIALS AND METHODS: The study was performed on S(57)Vl mice
      with transplanted Lewis lung carcinoma treated by intraperitoneal injections of L
      Arg at low or high doses (60 and 360 mg/kg body weight), CoQ10 (0.2 and 1.2 mg/kg
      body weight) or their combinations. Electron paramagnetic resonance was applied
      for analysis of mitochondrial electron transport chain, SoQ10 levels, free iron
      (FI), the level of NO, and the rate of superoxide radical generation. The
      activity of matrix metalloproteinase (MMP)-2 and -9 in tumor tissue was
      determined by zymography method in polyacrylamide gel. RESULTS: Administration of
      L-Arg at high doses caused an inhibition of tumor growth by 48 +/- 8.0%, increase
      of superoxide radical generation rate and NO levels to a value of 1.23 +/- 0.14
      and 2.26 +/- 0.31 nm/g tissue . min, and decreased activity of MMP-2 and -9 (3.55
      +/- 0.8 and 4.8 +/- 1.0 r.u., respectively). Treatment with L-Arg at low doses
      stimulated tumor growth and increased the levels of MMP-2 and -9 activities (8.44
      +/- 2.7 and 9.8 +/- 3.1 r.u., respectively). Administration of SoQ10 at high
      doses significantly decreased superoxide radical generation rate to the values of
      0.44 +/- 0.09 nm/g tissue . min, levels of free iron and NO, and caused tumor
      growth inhibition by 54 +/- 11.3%. The combined use of L-Arg and SoQ10 at high
      doses caused tumor growth inhibition by 51 +/- 7.4% compared to Lewis lung
      carcinoma-bearing untreated animals (p<0.05). CONCLUSIONS: Administration of L
      Arg and SoQ10 caused the dose-dependent effect on the rate of generation of
      superoxide radicals, level of ubisemyquinone, complexes NOFeS-proteins, levels of
      FI and NO. L-Arg at low doses positively modulated MMP-9 activity that promoted
      tumor progression. Upon combined use of L-Arg and SoQ10, superoxide radicals and
      NO form the redox state that causes decrease of MMP-2, -9 activities with
      consequent inhibition of tumor invasion and metastasis.

PMID- 27031717
TI  - Combined use of haemostatic system indices for evaluation of upper respiratory
      tract cancer progression.
AB  - AIM: To analyze whether comprehensive assessment of haemostatic system
      components, in particular, indices of coagulation and fibrinolytic systems along
      with functionally related proteins, could be indicative of upper respiratory
      tract (URT) cancer progression. MATERIALS AND METHODS: Indices of coagulation and
      fibrinolytic systems along with functionally related proteins, in particular,
      trypsin-like amidolytic activity, trypsin-like proteolytic activity, thrombin
      like amidolytic activity, elastase-like amidolytic activity, fibrinolytic
      activity, potential amidolytic plasmin activity, content of fibrinogen,
      antithrombin III, alpha1-proteinase inhibitor, and alpha2-macroglobulin, and
      prothrombin time were evaluated in blood plasma of patients with URT cancer of II
      (n = 10) and III (n = 25) stages with the use of routine biochemical methods.
      RESULTS: For both groups of patients with URT cancer there have been shown
      notable differences for the majority of the studied indices, especially the
      indexes of proteolytic activities, from these of healthy donors, and in the case
      of URT cancer of III stage they reached statistical significance. In contrary,
      the changes in the content of antithrombin III, alpha1-proteinase inhibitor, and
      alpha2-macroglobulin were insignificant. In both groups of patients significant
      increase of fibrinogen content has been registered, while the content of soluble
      fibrinogen didn't change. Also, in both groups of patients there a significant
      increase of potential activity of plasminogen was documented, while clot lysis
      time was significantly increased only in patients with III stage URT cancer.
      Multifactorial analysis of haemostatic system indices evidenced for efficacy of
      their combined use for evaluation of URT cancer progression risk. CONCLUSION:
      Combined use of fibrinogen and alpha2-macroglobulin content and the level of
      amidolytic thrombin-like activity could serve as an indicator of URT cancer
      progression.

PMID- 27031718
TI  - Study of cytogenetic abnormalities in G-CSF stimulated peripheral blood cells and
      non-stimulated bone marrow cells of patients with myelofibrosis.
AB  - The aim of the study was to improve cytogenetic diagnostics and monitoring of
      myelofibrosis and to reveal the spectrum of cytogenetic abnormalities in patients
      from Ukraine. MATERIALS AND METHODS: A total of 42 patients (23 females and 19
      males) with myelofibrosis was studied using different cytogenetic methods.
      Granulocyte colony-stimulating factor (G-CSF) was added by the new method during
      cultivation of peripheral blood (PB) cells from 31 patients for specific
      stimulation of mitotic divisions. Two patients underwent examination by
      fluorescent in situ hybridization method. RESULTS: In cell cultures of PB
      stimulated in vitro with G-CSF and in non-stimulated bone marrow chromosome
      abnormalities were found in 19 (45.2%) of all the patients. The spectrum of
      cytogenetic abnormalities of bone marrow and PB was the same in all of the
      patients. Aspiration of bone marrow was unsuccessful due to significant fibrosis
      in 10 (29.4%) of 34 patients. The study by fluorescent in situ hybridization
      method confirmed cytogenetic abnormalities revealed by G-method and discovered
      additional possibly normal subclone. CONCLUSIONS: Cytogenetic study of PB using
      in vitro G-CSF as a specific stimulant of mitosis instead of phytohemagglutinin
      revealed significant variety of chromosomal abnormalities in Ukrainian patients
      with myelofibrosis. This method could be a less invasive alternative to
      cytogenetic examination of bone marrow in the subgroup of patients with
      considerable fibrosis and consecutive changes. The usage of fluorescent in situ
      hybridization method supplemented karyotyping by G-banding method.

PMID- 27031720
TI  - Correlation between periodontal disease indices and lung cancer in Greek adults:
      a case-control study.
AB  - AIM: The aim of the present case-control study was to examine the possible
      associations between periodontal disease indices and the risk of lung cancer
      development in a sample of Greek out-patients referred to a medical and a dental
      private practice. MATERIALS AND METHODS: A total of 200 individuals were
      interviewed and underwent an oral clinical examination, and 64 of them were
      suffered from several histological types of lung cancer. The estimation of the
      possible associations between lung cancer as a dependent variable and periodontal
      disease indices as independent ones was carried out by using a multiple
      regression analysis model. RESULTS: Probing pocket depth (odds ratio (OR) = 2.72,
      95% confidence interval (CI) 1.05-7.06), clinical attachment loss (OR = 3.51, 95%
      CI 1.30-9.47) bleeding on probing (OR = 1.93, 95% CI 0.98-3.81) were
      significantly associated with the risk of developing lung cancer. Smoking (OR =
      2.49, 95% CI 1.20-5.17) was significantly associated with the mentioned risk,
      whereas it was consisted as a confounder regarding the estimated associations
      between moderate/severe clinical attachment loss and presence of bleeding on
      probing with the risk of developing lung cancer. CONCLUSION: Probing pocket depth
      as an index for periodontal disease severity was statistically significantly
      associated with the risk of developing lung cancer.

PMID- 27031719
TI  - Modelling of survival of patients with colon adenocarcinoma based on
      multivariable analysis of the state of cancer cell nuclear apparatus.
AB  - THE AIM: The creation of a mathematical model of survival in patients with colon
      adenocarcinoma based on multivariable analysis of the state of cancer cell
      nuclear apparatus. PATIENTS AND METHODS: The study was performed on 141 samples
      of biopsy materials or material obtained during surgical treatment of the
      patients with colon adenocarcinoma or benign colon neoplasms with the use of
      histological, morphometric, densitometric, immunohistochemical and mathematical
      methods. RESULTS: It has been shown that each discrete pattern of the state of
      adenocarcinoma cell nuclei (quantity of DNA, the number and volume of nuclear
      organizer regions, expression rates of Ki-67, Bcl-2 and p53) is prognostically
      invalid in the case of its separate use. Combination of these characteristics
      significantly enhances prognostic validity of the survival model. Based on
      equation of Cox proportional hazards, survival model of good quality for the
      patients with moderately and poorly differentiated adenocarcinoma and increased
      average DNA content in tumor cell nuclei has been created. CONCLUSION: The
      proposed survival model for colon adenocarcinoma demonstrates the quality twice
      superior to the model based on the use of tumor grade only (G) which in fact is
      presently used as a sole common independent histological criterion of prognosis.

PMID- 27031721
TI  - A nutrient mixture inhibits glioblastoma xenograft U-87 MG growth in male nude
      mice.
AB  - BACKGROUND: Brain tumors are highly aggressive tumors characterized by secretions
      of high levels of matrix metalloproteinase-2 and -9, leading to tumor growth,
      invasion and metastasis by digesting the basement membrane and extracellular
      matrix components. We previously demonstrated the effectiveness of a nutrient
      mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract in
      vitro: on activity of urokinase plasminogen activator, matrix metalloproteinases
      and TIMPs in various human glioblastoma (LN-18, T-98G and A-172) cell lines and
      on glioblastoma A-172 cell proliferation and Matrigel invasion. AIM: Our main
      objective in this study was to investigate the effect of the NM in vivo on human
      glioblastoma U-87 MG cell line. MATERIALS AND METHODS: Athymic male nude mice
      inoculated with 3.10(6) U-87 MG cells subcutaneously and were fed a regular diet
      or a regular diet supplemented with 0.5% NM. Four weeks later, the mice were
      sacrificed, the tumors were weighed and measured. The samples were studied
      histologically. RESULTS: NM inhibited tumor weight and tumor burden by 53% (p =
      0.015) and 48% (p = 0.010), respectively. CONCLUSIONS: These results suggest the
      therapeutic potential of NM as an adjuvant in the treatment of glioblastoma.

PMID- 27031723
TI  - 70th anniversary of the Lviv scientific school of oncology.
AB  - Contemporary development of scientific thought is fostered not by separate people
      but is a purposeful activity of a group of like-minded people armed with
      progressive ideas and modern technical equipment. Such schools appeared and work
      actively in the majo-rity of research and educational establishments, clinics,
      and universities. The Lviv school established in 1945 by Professor H.P.
      Kovtunovych and developed by Professor A.I. Hnatyshak and his disciples can serve
      as an example of a successful school of oncology that continues its activity and
      yields scientific results. This school appeared not out of the thin air. Medieval
      Lviv could boast of the first university on the territory of the present-day
      Ukraine. Many discoveries and endeavors that made a beneficial impact on the
      development of medicine in Eastern Europe were made in this city. For historical
      reasons, the city of Lviv used to belong to different state formations (Austria
      Hungary, Poland, the USSR; now it is a part of Ukraine), which could not but
      reflect on the staffing of doctor-researchers. This process acquired a special
      intensity in 1939-1945 when the research staff of the university changed
      substantially. Then, in 1945, H.P. Kovtunovych, the disciple of the prominent
      oncologist N.N. Petrov, came to Lviv and brought the ideas of St.-Petersburg onco
      logy to the Lviv ground. The Lviv school was influenced by the two times Nobel
      Prize winner Marie Sklodowska Curie, who facilitated the initiation of
      oncological radiology in Lviv. The article contains data on research done by the
      disciples of Professors H.P. Kovtunovych and A.I. Hnatyshak. The first ever
      teaching chair of oncology in the USSR was founded in Lviv (1966), as well as the
      first Ukrainian hospice--an institution for palliative care for the oncological
      patients. The Lviv oncology center is one of the biggest and best-equipped
      oncology centers in Ukraine. An organic combination of theory and clinical
      practice has always been the guiding principle of the Lviv school of oncology.
      Presently, the Lviv school of oncology unites six doctors of sciences, a large
      collective of educators and researchers, as well as practitioners of the center
      of oncology. The school maintains close scientific and practical ties with
      oncologists of Ukraine as well as with leading oncological centers of Europe and
      America.

PMID- 27031722
TI  - miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an
      Iranian subpopulation.
AB  - AIM: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or
      tumor suppressors. The single nucleotide polymorphisms in miRNAs potentially can
      alter miRNA-binding sites on target genes as well as affecting miRNAs expression.
      The present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant
      on breast cancer (BC) risk. MATERIALS AND METHODS: This case-control study
      conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of
      miR-608 rs4919510 was done using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method. RESULTS: Our findings showed that GC
      genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95%
      confidence interval (CI) 0.28-0.88, p = 0.018) compared to CC genotype.
      Furthermore the G allele decreased the risk of BC (OR = 0.53, 95%CI 0.30-0.92, p
      = 0.024). No significant association was found between miR-609 genotypes and
      clinicopathological characteristics of BC patients (p >0.05). CONCLUSION: Our
      findings indicate that miR-608 polymorphism might be associated with decreased
      risk of BC in an Iranian subpopulation. Further large-scale studies with
      different ethnicities are needed to verify our findings.

PMID- 27031726
TI  - Polarity-Dependent Misperception of Subjective Visual Vertical during and after
      Transcranial Direct Current Stimulation (tDCS).
AB  - Pathologic tilt of subjective visual vertical (SVV) frequently has adverse
      functional consequences for patients with stroke and vestibular disorders.
      Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus
      can produce a transitory tilt on SVV in healthy subjects. However, the effect of
      transcranial direct current stimulation (tDCS) on SVV has never been
      systematically studied. We investigated whether bilateral tDCS over the temporal
      parietal region could result in both online and offline SVV misperception in
      healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot
      study, thirteen healthy subjects performed tests of SVV before, during and after
      the tDCS applied over the temporal-parietal region in three conditions used on
      different days: right anode/left cathode; right cathode/left anode; and sham.
      Subjects were blind to the tDCS conditions. Montage-specific current flow
      patterns were investigated using computational models. SVV was significantly
      displaced towards the anode during both active stimulation conditions when
      compared to sham condition. Immediately after both active conditions, there were
      rebound effects. Longer lasting after-effects towards the anode occurred only in
      the right cathode/left anode condition. Current flow models predicted the
      stimulation of temporal-parietal regions under the electrodes and deep clusters
      in the posterior limb of the internal capsule. The present findings indicate that
      tDCS over the temporal-parietal region can significantly alter human SVV
      perception. This tDCS approach may be a potential clinical tool for the treatment
      of SVV misperception in neurological patients. 

PMID- 27031727
TI  - Management of Severe and Complex Hypopharyngeal and/or Laryngotracheal Stenoses
      by Various Open Surgical Procedures: A Retrospective Study of Seventeen Patients.
AB  - OBJECTIVE: To systematically study various surgical approaches for treating
      complex hypopharyngeal and/or laryngotracheal stenoses at a variety of sites and
      levels. PATIENTS AND METHODS: We retrospectively analyzed the treatment of 17
      patients with severe and complex hypopharyngeal and/or laryngotracheal stenosis
      at various sites and levels of severity. All of the 17 patients initially had a
      tracheostomy. Thirteen had failed the previous laser lysis and/or dilation
      treatment. Given the high severity and complexity of stenosis, all of these
      patients were treated by open surgical reconstruction techniques using repairing
      grafts (flaps), followed by stenting. RESULTS: Thirteen of 17 patients had
      successful decannulation 1-8 months post-operation and had stable airway and
      adequate vocal and swallow function. Two patients with complex hypopharyngeal and
      esophageal stenosis had unsuccessful decannulation. Follow-up was lost in 1
      patient with complex hypopharyngeal and esophageal stenosis and 1 patient with
      original hypopharyngeal stenosis and recurrent thoracotracheal stenosis.
      CONCLUSION: Despite the failure by the regular treatments using laser lysis
      and/or dilation therapy, severe and complex hypopharyngeal and/or laryngotracheal
      stenosis may be successfully treated by variable open surgical reconstruction
      techniques using different grafts (flaps) depending on the site and severity of
      the stenosis.

PMID- 27031728
TI  - Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the
      Antifungal Effects of Terbinafine.
AB  - Terbinafine is a recommended therapeutic alternative for patients with
      sporotrichosis who cannot use itraconazole due to drug interactions or side
      effects. Melanins are involved in resistance to antifungal drugs and Sporothrix
      species produce three different types of melanin. Therefore, in this study we
      evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs.
      Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations
      (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown
      in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to
      the MIC determined by the CLSI standard protocol for S. schenckii susceptibility
      to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were
      determined in the presence of inhibitors to three pathways of melanin synthesis,
      we observed, in four strains, an increase in terbinafine susceptibility in the
      presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii
      strain grown in the presence of L-DOPA had a higher MFC value when compared to
      the control. Growth curves in presence of 2*MIC concentrations of terbinafine
      showed that pyomelanin and, to a lesser extent, eumelanin were able to protect
      the fungi against the fungicidal effect of this antifungal drug. Our results
      suggest that melanin protects the major pathogenic species of the Sporothrix
      complex from the effects of terbinafine and that the development of new
      antifungal drugs targeting melanin synthesis may improve sporotrichosis
      therapies. 

PMID- 27031730
TI  - Cerebrospinal Fluid Biomarkers for Huntington's Disease.
AB  - Cerebrospinal fluid (CSF) is enriched in brain-derived components and represents
      an accessible and appealing means of interrogating the CNS milieu to study
      neurodegenerative diseases and identify biomarkers to facilitate the development
      of novel therapeutics. Many such CSF biomarkers have been proposed for
      Huntington's disease (HD) but none has been validated for clinical trial use.
      Across many studies proposing dozens of biomarker candidates, there is a notable
      lack of statistical power, consistency, rigor and validation. Here we review
      proposed CSF biomarkers including neurotransmitters, transglutaminase activity,
      kynurenine pathway metabolites, oxidative stress markers, inflammatory markers,
      neuroendocrine markers, protein markers of neuronal death, proteomic approaches
      and mutant huntingtin protein itself. We reflect on the need for large-scale,
      standardized CSF collections with detailed phenotypic data to validate and
      qualify much-needed CSF biomarkers for clinical trial use in HD. 

PMID- 27031729
TI  - "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to
      Germany from Vacation in Southern Africa.
AB  - A 26 year-old female patient presented to the Tropical Medicine outpatient unit
      of the Ludwig Maximilians-University in Munich with febrile illness after
      returning from Southern Africa, where she contracted a bite by a large mite-like
      arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained
      blood smears and treatment was started with doxycycline for suspected tick-borne
      relapsing fever. The patient eventually recovered after developing a slight
      Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA
      blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia
      duttonii, and B. parkeri. Further sequences obtained from the flagellin gene
      (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B.
      duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of
      0.086 to B. hermsii in genetic analysis and only distant relations with classic
      Old World relapsing fever species. This revealed the presence of a novel species
      of tick-borne relapsing fever spirochetes that we propose to name "Candidatus
      Borrelia kalaharica", as it was contracted from an arthropod bite in the Kalahari
      Desert belonging to both, Botswana and Namibia, a region where to our knowledge
      no relapsing fever has been described so far. Interestingly, the novel species
      shows more homology to New World relapsing fever Borrelia such as B. parkeri or
      B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. 

PMID- 27031731
TI  - Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3
      Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse
      Model of Huntington's Disease.
AB  - BACKGROUND: Impairments in energy metabolism are implicated in Huntington's
      disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate
      dehydrogenase (SDH), the main element of complex II, are observed post mortem in
      the brains of HD patients, and energy metabolism defects have been identified in
      both presymptomatic and symptomatic HD patients. OBJECTIVE: Chemical
      preconditioning with 3-nitropropionic acid (3-NP), an irreversible inhibitor of
      SDH, has been shown to increase tolerance against experimental hypoxia in both
      heart and brain. Here we studied the effect of chronic preconditioning in the
      R6/2 mouse model of HD using mice carrying CAG repeat lengths of either 250 or
      400 repeats. Both are transgenic fragment models, with 250CAG mice having a more
      rapid disease progression than 400CAG mice. METHODS: Low doses of 3-NP (24 mg/kg)
      were administered via the drinking water and the effect on phenotype progression
      and cognition function assessed. RESULTS: After 3-NP treatment there were
      significant improvements in all aspects of the behavioural phenotype, apart from
      body weight, with timing and magnitude of improvements dependent on both CAG
      repeat length and sex. Specifically, a delay in the deterioration of general
      health (as shown by delayed onset of glycosuria and increased survival) was seen
      in both male and female 400CAG mice and in female 250CAG mice and was consistent
      with improved appearance of 3-NP treated R6/2 mice. Male 250CAG mice showed
      improvements but these were short term, and 3-NP treatment eventually had
      deleterious effects on their survival rate. When cognitive performance of 250CAG
      mice was assessed using a two-choice discrimination touchscreen task, we found
      that female mice showed significant improvements. DISCUSSION: Together, our
      results support the idea that energy metabolism contributes to the pathogenesis
      of HD, and suggest that improving energy deficits might be a therapeutically
      useful target.

PMID- 27031734
TI  - Personality Predicts Utilization of Mindfulness-Based Stress Reduction During and
      Post-Intervention in a Community Sample of Older Adults.
AB  - OBJECTIVES: Mindfulness-based stress reduction (MBSR) is a promising intervention
      for older adults seeking to improve quality of life. More research is needed,
      however, to determine who is most willing to use the four techniques taught in
      the program (yoga, sitting meditation, informal meditation, and body scanning).
      This study evaluated the relationship between the Big Five personality dimensions
      (neuroticism, extraversion, openness to experience, conscientiousness, and
      agreeableness) and use of MBSR techniques both during the intervention and at a 6
      month follow-up. The hypothesis was that those with higher levels of openness and
      agreeableness would be more likely to use the techniques. METHODS: Participants
      were a community sample of 100 older adults who received an 8-week manualized
      MBSR intervention. Personality was assessed at baseline by using the 60-item NEO
      Five-Factor Inventory. Use of MBSR techniques was assessed through weekly
      practice logs during the intervention and a 6-month follow-up survey. Regression
      analyses were used to examine the association between each personality dimension
      and each indicator of MBSR use both during and after the intervention. RESULTS:
      As hypothesized, openness and agreeableness predicted greater use of MBSR both
      during and after the intervention, while controlling for demographic differences
      in age, educational level, and sex. Openness was related to use of a variety of
      MBSR techniques during and after the intervention, while agreeableness was
      related to use of meditation techniques during the intervention. Mediation
      analysis suggested that personality explained postintervention MBSR use, both
      directly and by fostering initial uptake of MBSR during treatment. CONCLUSIONS:
      Personality dimensions accounted for individual differences in the use of MBSR
      techniques during and 6 months after the intervention. Future studies should
      consider how mental health practitioners would use these findings to target and
      tailor MBSR interventions to appeal to broader segments of the population.

PMID- 27031732
TI  - Partial Amelioration of Peripheral and Central Symptoms of Huntington's Disease
      via Modulation of Lipid Metabolism.
AB  - BACKGROUND: Huntington's disease (HD) is a fatal, inherited neurodegenerative
      disorder characterized by uncontrollable dance-like movements, as well as
      cognitive deficits and mood changes. A feature of HD is a metabolic disturbance
      that precedes neurological symptoms. In addition, brain cholesterol synthesis is
      significantly reduced, which could hamper synaptic transmission. OBJECTIVE:
      Alterations in lipid metabolism as a potential target for therapeutic
      intervention in the R6/2 mouse model of HD were examined. METHODS:
      Electrophysiological recordings in vitro examined the acute effects of
      cholesterol-modifying drugs. In addition, behavioral testing, effects on synaptic
      activity, and measurements of circulating and brain tissue concentrations of
      cholesterol and the ketone beta-hydroxybutyrate (BHB), were examined in
      symptomatic R6/2 mice and littermate controls raised on normal chow or a
      ketogenic diet (KD). RESULTS: Whole-cell voltage clamp recordings of striatal
      medium-sized spiny neurons (MSNs) from symptomatic R6/2 mice showed increased
      frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) compared with
      littermate controls. Incubation of slices in cholesterol reduced the frequency of
      large-amplitude sIPSCs. Addition of BHB or the Liver X Receptor (LXR) agonist
      T0901317 reduced the frequency and amplitude of sIPSCs. Surprisingly, incubation
      in simvastatin to reduce cholesterol levels also decreased the frequency of
      sIPSCs. HD mice fed the KD lost weight more gradually, performed better in an
      open field, had fewer stereotypies and lower brain levels of cholesterol than
      mice fed a regular diet. CONCLUSIONS: Lipid metabolism represents a potential
      target for therapeutic intervention in HD. Modifying cholesterol or ketone levels
      acutely in the brain can partially rescue synaptic alterations, and the KD can
      prevent weight loss and improve some behavioral abnormalities.

PMID- 27031736
TI  - Stabilization of a Strained Heteroradialene by Peripheral Electron
      Delocalization.
AB  - Dimethylamine and 2,4,6-triformylphloroglucinol react to form a product with a
      highly contorted nonplanar geometry due to favorable electron delocalization.
      This new heteroradialene compound has been studied by X-ray diffraction, variable
      temperature multinuclear NMR spectroscopy, IR spectroscopy, UV-vis spectroscopy,
      and ab initio calculations. Electron delocalization throughout the periphery of
      the central ring leads to a structure that retains very little of the aromatic
      characteristics of the starting material. 

PMID- 27031737
TI  - Oxygen Evolution Reaction Dynamics, Faradaic Charge Efficiency, and the Active
      Metal Redox States of Ni-Fe Oxide Water Splitting Electrocatalysts.
AB  - Mixed Ni-Fe oxides are attractive anode catalysts for efficient water splitting
      in solar fuels reactors. Because of conflicting past reports, the catalytically
      active metal redox state of the catalyst has remained under debate. Here, we
      report an in operando quantitative deconvolution of the charge injected into the
      nanostructured Ni-Fe oxyhydroxide OER catalysts or into reaction product
      molecules. To achieve this, we explore the oxygen evolution reaction dynamics and
      the individual faradaic charge efficiencies using operando differential
      electrochemical mass spectrometry (DEMS). We further use X-ray absorption
      spectroscopy (XAS) under OER conditions at the Ni and Fe K-edges of the
      electrocatalysts to evaluate oxidation states and local atomic structure motifs.
      DEMS and XAS data consistently reveal that up to 75% of the Ni centers increase
      their oxidation state from +2 to +3, while up to 25% arrive in the +4 state for
      the NiOOH catalyst under OER catalysis. The Fe centers consistently remain in the
      +3 state, regardless of potential and composition. For mixed Ni100-xFex
      catalysts, where x exceeds 9 atomic %, the faradaic efficiency of O2 sharply
      increases from ~30% to 90%, suggesting that Ni atoms largely remain in the
      oxidation state +2 under catalytic conditions. To reconcile the apparent low
      level of oxidized Ni in mixed Ni-Fe catalysts, we hypothesize that a kinetic
      competition between the (i) metal oxidation process and the (ii) metal reduction
      step during O2 release may account for an insignificant accumulation of
      detectable high-valent metal states if the reaction rate of process (ii)
      outweighs that of (i). We conclude that a discussion of the superior catalytic
      OER activity of Ni-FeOOH electrocatalysts in terms of surface catalysis and redox
      inactive metal sites likely represents an oversimplification that fails to
      capture essential aspects of the synergisms at highly active Ni-Fe sites.

PMID- 27031735
TI  - Proteomic study of acute respiratory distress syndrome: current knowledge and
      implications for drug development.
AB  - The acute respiratory distress syndrome (ARDS) is a common cause of acute
      respiratory failure, and is associated with substantial mortality and morbidity.
      Dozens of clinical trials targeting ARDS have failed, with no drug specifically
      targeting lung injury in widespread clinical use. Thus, the need for drug
      development in ARDS is great. Targeted proteomic studies in ARDS have identified
      many key pathways in the disease, including inflammation, epithelial injury,
      endothelial injury or activation, and disordered coagulation and repair. Recent
      studies reveal the potential for proteomic changes to identify novel
      subphenotypes of ARDS patients who may be most likely to respond to therapy and
      could thus be targeted for enrollment in clinical trials. Nontargeted studies of
      proteomics in ARDS are just beginning and have the potential to identify novel
      drug targets and key pathways in the disease. Proteomics will play an important
      role in phenotyping of patients and developing novel therapies for ARDS in the
      future.

PMID- 27031738
TI  - The Economic Impact of Intensive Care Management for High-Cost Medically Complex
      Patients: An Evaluation of New Mexico's Care One Program.
AB  - High-cost, medically complex patients have been a challenging population to
      manage in the US health care system, in terms of both improving health outcomes
      and containing costs. This paper evaluated the economic impact of Care One, an
      intensive care management program (data analysis, evaluation, empanelment,
      specialist disease management, nurse case management, and social support)
      designed to target the most expensive 1% of patients in a university health care
      system. Data were collected for a cohort of high-cost, medically complex patients
      (N = 753) who received care management and a control group (N = 794) of similarly
      complex health system users who did not receive access to the program. A pre-post
      empirical model estimated the Care One program to be associated with a per
      patient reduction in billed charges of $92,227 (95% confidence interval [CI]:
      $83,988 to $100,466). A difference-in-difference model, which utilized the
      control group, estimated a per-patient reduction in billing charges of $44,504
      (95% CI: $29,195 to $59,813). Results suggest that care management for high-cost,
      medically complex patients in primary care can reduce costs compared to a control
      group. In addition, significant reversion to the mean is found, providing support
      for the use of a difference-in-difference estimator when evaluating health
      programs for high-cost, medically complex patients.

PMID- 27031739
TI  - Whole Body Periodic Acceleration Improves Muscle Recovery after Eccentric
      Exercise.
AB  - INTRODUCTION: The aim of this study was to determine whether whole body periodic
      acceleration (pGz) could improve muscle recovery after unaccustomed eccentric
      exercise (EE). METHODS: Downhill treadmill running was used to elicit EE-induced
      muscle damage in mice, and pGz treatment (480 cycles per minute, 1 h.d) was
      applied daily for 10 d after the initial EE bout (day 0). Every 2 d during the
      pGz treatment course starting at day 0, we 1) assessed intracellular Ca and Na
      concentrations and membrane potential (as indicators of intracellular ion
      dysfunction) in vivo in gastrocnemius muscle from anesthetized animals and 2)
      quantified creatine kinase (CK), tumor necrosis factor alpha (TNF-alpha),
      monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and interleukin
      10 (IL-10) concentrations in plasma or muscle lysates (as indicators of muscle
      damage and inflammation). RESULTS: EE significantly increased intracellular Ca
      and Na, CK, TNF-alpha, MCP-1, IL-6, and IL-10, all of which peaked on day 2 with
      the exception of IL-10 and declined slowly over 10 d of recovery. pGz treatment
      after the EE bout mitigated ion dyshomeostasis and expedited recuperation to
      control values after 6 d of treatment. pGz treatment also accelerated the
      normalization of CK, TNF-alpha, MCP-1, and IL-6 while further increasing IL-10
      concentrations. The nitric oxide synthase inhibitor L-N-nitroarginine methyl
      ester, administered in drinking water before and maintained throughout the
      treatment course, was sufficient to abrogate the salutary effects of pGz after
      EE. CONCLUSIONS: The present study demonstrates whole body periodic acceleration
      as an effective therapeutic strategy to accelerate muscle recovery after EE
      induced skeletal muscle injury, as indicated by a faster normalization of all the
      studied parameters.

PMID- 27031740
TI  - Mechanical Alterations to Repeated Treadmill Sprints in Normobaric Hypoxia.
AB  - PURPOSE: Compelling evidence suggests larger performance decrements during
      hypoxic versus normoxic repeated sprinting. Yet the underlying mechanical
      alterations have not been thoroughly investigated. Therefore, we examined the
      effects of different levels of normobaric hypoxia on running mechanical
      performance during repeated treadmill sprinting. METHODS: Thirteen team sport
      athletes performed eight 5-s sprints with 25 s of passive recovery on an
      instrumented treadmill in either normoxia near sea level (SL; FiO2 = 20.9%),
      moderate normobaric hypoxia (MH; FiO2 = 16.8%; corresponding to ~1800 m
      altitude), or severe normobaric hypoxia (SH; FiO2 = 13.3%; ~3600 m). RESULTS: Net
      power output in the horizontal direction did not differ (P > 0.05) between
      conditions for the first sprint (mean +/- SD, pooled values: 13.09 +/- 1.97 W.kg)
      but was lower for the eight sprints in SH compared with SL (-7.3% +/- 5.5%, P <
      0.001) and MH (-7.1% +/- 5.9%, P < 0.01), with no difference between SL and MH
      (+0.1% +/- 8.0%, P = 1.00). Sprint decrement score was similar between conditions
      (pooled values: -11.4% +/- 7.9%, P = 0.49). Mean vertical, horizontal, and
      resultant ground reaction forces decreased (P < 0.001) from the first to the last
      repetition in all conditions (pooled values: -2.4% +/- 1.9%, -8.6% +/- 6.5%, and 
      2.4% +/- 1.9%). This was further accompanied by larger kinematic (mainly contact
      time: +4.0% +/- 2.9%, P < 0.001, and +3.3% +/- 3.6%, P < 0.05, respectively;
      stride frequency: -2.3% +/- 2.0%, P < 0.01, and -2.3% +/- 2.8%, P < 0.05,
      respectively) and spring-mass characteristics (mainly vertical stiffness: -6.0%
      +/- 3.9% and -5.1% +/- 5.7%, respectively, P < 0.01) fatigue-induced changes in
      SH compared with SL and MH. CONCLUSION: In SH, impairments in repeated sprint
      ability and in associated kinetics/kinematics and spring-mass characteristics
      exceed those observed near SL and in MH (i.e., no or minimal difference).
      Specifically, SH accentuates the repeated sprint ability fatigue-related
      inability to effectively apply forward-oriented ground reaction force and to
      maintain vertical stiffness and stride frequency.

PMID- 27031741
TI  - Fatigue: Where Did We Come from and How Did We Get Here?
AB  - : This paper highlights some key concepts related to fatigue and the seminal role
      of the 1981 Ciba Foundation Symposia "Human Muscle Fatigue: Physiological
      Mechanisms" chaired by R.H.T. Edwards in consolidating key ideas that have moved
      the study of fatigue forward since that time. I also consider these concepts in
      their historical context via the pioneering work of the Italian physiologist and
      social activist Angelo Mosso in the late 1800s. Finally, fatigue as a
      multidimensional concept with implications beyond muscle physiology is
      considered.

PMID- 27031743
TI  - The Etiology of Muscle Fatigue Differs between Two Electrical Stimulation
      Protocols.
AB  - PURPOSE: This study aimed at investigating the mechanisms involved in the force
      reduction induced by two electrical stimulation (ES) protocols that were designed
      to activate motor units differently. METHODS: The triceps surae of 11 healthy
      subjects (8 men; age, ~28 yr) was activated using ES applied over the tibial
      nerve. Two ES protocols (conventional [CONV]: 20 Hz, 0.05 ms vs wide-pulse high
      frequency [WPHF]: 80 Hz, 1 ms) were performed and involved 40 trains (6 s on-6 s
      off) delivered at an intensity (IES) evoking 20% of maximal voluntary
      contraction. To analyze the mechanical properties of the motor units activated at
      IES, force-frequency relation was evoked before and after each protocol. H-reflex
      and M-wave responses evoked by the last stimulation pulse were also assessed
      during each ES protocol. Electromyographic responses (?EMG) were recorded after
      each train to analyze the behavior of the motor units activated at IES. Metabolic
      variables, including relative concentrations of phosphocreatine and inorganic
      phosphate as well as intracellular pH, were assessed using P-MR spectroscopy
      during each protocol. RESULTS: Larger H-reflex amplitudes were observed during
      WPHF as compared with CONV, whereas opposite findings were observed for M-wave
      amplitudes. Despite this difference, both the force reduction (-26%) and
      metabolic changes were similar between the two protocols. The CONV protocol
      induced a rightward shift of the force-frequency relation, whereas a significant
      reduction of the ?EMG evoked at IES was observed only for the WPHF. CONCLUSIONS:
      These results suggest that a decreased number of active motor units mainly
      contributed to WPHF-induced force decrease, whereas intracellular processes were
      most likely involved in the force reduction occurring during CONV stimulation.

PMID- 27031742
TI  - Critical Power: An Important Fatigue Threshold in Exercise Physiology.
AB  - : The hyperbolic form of the power-duration relationship is rigorous and highly
      conserved across species, forms of exercise, and individual muscles/muscle
      groups. For modalities such as cycling, the relationship resolves to two
      parameters, the asymptote for power (critical power [CP]) and the so-called W'
      (work doable above CP), which together predict the tolerable duration of exercise
      above CP. Crucially, the CP concept integrates sentinel physiological profiles
      respiratory, metabolic, and contractile-within a coherent framework that has
      great scientific and practical utility. Rather than calibrating equivalent
      exercise intensities relative to metabolically distant parameters such as the
      lactate threshold or VO2max, setting the exercise intensity relative to CP
      unifies the profile of systemic and intramuscular responses and, if greater than
      CP, predicts the tolerable duration of exercise until W' is expended, VO2max is
      attained, and intolerance is manifested. CP may be regarded as a "fatigue
      threshold" in the sense that it separates exercise intensity domains within which
      the physiological responses to exercise can (<CP) or cannot (>CP) be stabilized.
      The CP concept therefore enables important insights into 1) the principal loci of
      fatigue development (central vs. peripheral) at different intensities of exercise
      and 2) mechanisms of cardiovascular and metabolic control and their modulation by
      factors such as O2 delivery. Practically, the CP concept has great potential
      application in optimizing athletic training programs and performance as well as
      improving the life quality for individuals enduring chronic disease.

PMID- 27031744
TI  - Comparison of Sedentary Estimates between activPAL and Hip- and Wrist-Worn
      ActiGraph.
AB  - PURPOSE: Sedentary behavior is an emerging independent health risk factor. The
      accuracy of measuring sedentary time using accelerometers may depend on the wear
      location. This study in older adults evaluated the accuracy of various hip- and
      wrist-worn ActiGraph accelerometer cutoff points to define sedentary time using
      the activPAL as the reference method. METHODS: Data from 62 adults (mean age,
      78.4 yr) of the Aging Research Evaluating Accelerometry study were used.
      Participants simultaneously wore an activPAL accelerometer on the thigh and
      ActiGraph accelerometers on the hip, dominant, and nondominant wrist for 7 d in a
      free-living environment. Using the activPAL as the reference criteria, we
      compared classification of sedentary time to hip-worn and wrist-worn ActiGraph
      accelerometers over a range of cutoff points for both 60-s and 15-s epochs.
      RESULTS: The optimal cutoff point for the hip vertical axis was <22 counts per
      minute with an area under the curve (AUC) of 0.85; the optimal hip vector
      magnitude cutoff point was <174 counts per minute with an AUC of 0.89. For the
      dominant wrist, the optimal vector magnitude cutoff point to define sedentary
      time was <2303 counts per minute (AUC, 0.86) and for the nondominant wrist <1853
      counts per minute (AUC, 0.86). The optimal 15-s cutoff points resulted in lower
      agreements compared with activPAL. CONCLUSIONS: Hip- and wrist-worn ActiGraph
      data may be used to define sedentary time with a moderate to high accuracy when
      compared with activPAL. The observed optimal cutoff point for hip vertical axis
      <22 counts per minute is substantially lower than the standard <100 counts per
      minute. It is unknown how these optimal cutoff points perform in different
      populations. Results on an individual basis should therefore be interpreted with
      caution.

PMID- 27031745
TI  - Muscle Signaling in Exercise Intolerance: Insights from the McArdle Mouse Model.
AB  - INTRODUCTION: We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X)
      of the McArdle disease (myophosphorylase deficiency). One mechanistic approach to
      unveil the molecular alterations caused by myophosphorylase deficiency, which is
      arguably the paradigm of "exercise intolerance," is to compare the skeletal
      muscle tissue of McArdle, heterozygous, and healthy (wild-type [wt]) mice.
      METHODS: We analyzed in quadriceps muscle of p.R50X/p.R50X (n = 4), p.R50X/wt (n
      = 6), and wt/wt mice (n = 5) (all male, 8 wk old) molecular markers of energy
      sensing pathways, oxidative phosphorylation and autophagy/proteasome systems,
      oxidative damage, and sarcoplasmic reticulum Ca handling. RESULTS: We found a
      significant group effect for total adenosine monophosphate-(AMP)-activated
      protein kinase (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P = 0.012 and
      0.033), with higher mean values in p.R50X/p.R50X mice versus the other two
      groups. The absence of a massive accumulation of ubiquitinated proteins,
      autophagosomes, or lysosomes in p.R50X/p.R50X mice suggested no major alterations
      in autophagy/proteasome systems. Citrate synthase activity was lower in
      p.R50X/p.R50X mice versus the other two groups (P = 0.036), but no statistical
      effect existed for respiratory chain complexes. We found higher levels of 4
      hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared
      with the wt/wt group (P = 0.011). Sarco(endo)plasmic reticulum ATPase 1 levels
      detected at 110 kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice
      compared with wt/wt animals (P = 0.076), but their enzyme activity was normal. We
      also found an accumulation of phosphorylated sarco(endo)plasmic reticulum ATPase
      1 in p.R50X/p.R50X animals. CONCLUSION: Myophosphorylase deficiency causes
      alterations in sensory energetic pathways together with some evidence of
      oxidative damage and alterations in Ca handling but with no major alterations in
      oxidative phosphorylation capacity or autophagy/ubiquitination pathways, which
      suggests that the muscle tissue of patients is likely to adapt overall favorably
      to exercise training interventions.

PMID- 27031746
TI  - CA-MRSA Infection Incidence and Care in High School and Intercollegiate
      Athletics.
AB  - PURPOSE: Position papers offer solutions to manage community-associated
      methicillin-resistant Staphylococcus aureus (CA-MRSA), yet few studies establish
      the infection rate, management protocols, and referral practices among student
      athletes. Over the 2012-2013 and 2013-2014 school years, we assessed the annual
      CA-MRSA infection incidence, sport risk, referral practices, and management steps
      among high school and intercollegiate athletics. METHODS: This study targeted
      high school and intercollegiate athletic programs in the Northeastern United
      States. For the 2012-2013 study, 156 athletic trainers completed a one-time
      questionnaire. In the 2013-2014 study, 87 athletic trainers reported data
      bimonthly during the academic year. Each questionnaire targeted demographic
      information, physician-confirmed CA-MRSA infection occurrence, and management of
      CA-MRSA infections and bacterial skin lesions. RESULTS: The CA-MRSA infection
      incidence was 15.5 per 10,000 athletes (95% confidence interval [CI], 13-19) in
      2012-2013 and 16.3 per 10,000 athletes (95% CI, 13-21) in 2013-2014. The CA-MRSA
      infection incidence was higher in wrestling and football compared to the general
      student-athlete population. During the 2012-2013 study, the wrestling incidence
      rate was 90.2 per 10,000 (95% CI, 62-132); the football incidence rate was 42.3
      per 10,000 (95% CI, 31-59). In the 2013-2014 study, the wrestling incidence rate
      was 89.0 per 10,000 (95% CI, 50-158); the football incidence rate was 61.4 per
      10,000 (95% CI, 42-90). In both studies, primary care and general physicians
      received over 60% (2012-2013: 60.5%, n = 133; 2013-2014: 66.5%, n = 125) of
      referrals. In the 2012-2013 study, respondents indicated that student-athlete
      isolation and setting decontamination were common management steps used (58.1%, n
      = 306). CONCLUSIONS: The incidence of CA-MRSA infections among student-athletes
      remains high. Therefore, it is critical that sports medicine providers
      continually reassess management protocols and best practices.

PMID- 27031747
TI  - Double-Poling Biomechanics of Elite Cross-country Skiers: Flat versus Uphill
      Terrain.
AB  - INTRODUCTION: In light of the recent revolutionary change in the use of the
      double-poling (DP) technique in cross-country skiing, our purpose was to compare
      the associated kinetics and kinematics on flat (DPflat) and uphill terrain
      (DPup), as well as to identify factors that determine performance. METHODS:
      Thirteen elite male cross-country skiers completed two incremental speed tests
      (Vpeak) involving roller skiing with the DP technique at moderate (13 and 24
      km.h) and high speed (15 and 28.5 km.h) on a treadmill that was flat (1 degrees )
      or tilted uphill (7 degrees ). Pole forces and three-dimensional whole-body
      kinematics were monitored simultaneously. RESULTS: In comparison to DPflat,
      during DPup, swing times were much shorter (-48%) and peak pole forces greater
      (+13%) and generated later during the poling phase (+68%), with higher impulses
      for all force components (+87%-123%). Furthermore, pole forces were 18% more
      effectively oriented for propulsion. During DPup, the skiers demonstrated more
      flexed elbows, as well as shoulder angles that were less flexed in the forward
      direction and less abducted throughout the poling phase, together with more
      highly flexed knee and ankle joints, a more upright thorax, less flexed hips, and
      a shortened backward swing after pole off. With DPup, the skiers raised their
      center of mass 25% more, attaining maximal heel raise and maximal vertical
      position at a timepoint closer to pole plant compared with flat. On the uphill
      incline, the magnitude of Vpeak was positively related to body mass, relative
      pole length (% body height), and magnitude of heel raise. CONCLUSIONS: The
      present findings provide novel insights into the coordination, kinetics and
      kinematics of elite skiers while DP on flat and uphill terrain.

PMID- 27031748
TI  - The Effect of Physical Activity on Passive Leg Movement-Induced Vasodilation with
      Age.
AB  - INTRODUCTION: Because of reduced nitric oxide (NO) bioavailability with age,
      passive leg movement (PLM)-induced vasodilation is attenuated in older sedentary
      subjects and, unlike the young subjects, cannot be augmented by posture-induced
      elevations in femoral perfusion pressure. However, whether vasodilator function
      assessed with PLM, and therefore NO bioavailability, is preserved in older
      individuals with greater physical activity and fitness is unknown. METHODS: PLM
      was performed on four subject groups: young sedentary (Y, 23 +/- 1 yr, n = 12),
      old sedentary (OS, 73 +/- 2 yr, n = 12), old active (OA, 71 +/- 2 yr, n = 10),
      and old endurance trained (OT, 72 +/- 1 yr, n = 10) in the supine and upright
      seated posture. Hemodynamics were measured using ultrasound Doppler and finger
      photoplethysmography. RESULTS: In the supine posture, PLM-induced peak change in
      leg vascular conductance was significantly attenuated in the OS compared with the
      young subjects (OS = 4.9 +/- 0.5, Y = 6.9 +/- 0.7 mL.min.mm Hg) but was not
      different from the young in the OA and OT (OA = 5.9 +/- 1.0, OT = 5.4 +/- 0.4
      mL.min.mm Hg). The upright-seated posture significantly augmented peak change in
      leg vascular conductance in all but the OS (OS = 4.9 +/- 0.5, Y = 11.8 +/- 1.3,
      OA = 7.3 +/- 0.8, OT = 8.1 +/- 0.8 mL.min.mm Hg), revealing a significant
      vasodilatory reserve capacity in the other groups (Y = 4.92 +/- 1.18, OA = 1.37
      +/- 0.55, OT = 2.76 +/- 0.95 mL.min.mm Hg). CONCLUSIONS: As PLM predominantly
      reflects NO-mediated vasodilation, these findings support the idea that
      augmenting physical activity and fitness can protect NO bioavailability,
      attenuating the deleterious effects of advancing age on vascular function.

PMID- 27031749
TI  - Hepatitis B virus nuclear export elements: RNA stem-loop alpha and beta, key
      parts of the HBV post-transcriptional regulatory element.
AB  - Many viruses contain RNA elements that modulate splicing and/or promote nuclear
      export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus
      (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional
      regulatory element' (PRE). This element promotes expression from these naturally
      intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is
      used to enhance expression in gene therapy and other expression vectors. These
      PRE are likely to act through a combination of mechanisms, including promotion of
      RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2
      conserved RNA cis-acting stem-loop (SL) structures, SLalpha and SLbeta. They are
      within the coding regions of polymerase (P) gene, and both P and X genes,
      respectively. Based on previous studies using mutagenesis and/or nuclear magnetic
      resonance (NMR), here we propose 2 covariance models for SLalpha and SLbeta. The
      model for the 30-nucleotide SLalpha contains a G-bulge and a CNGG(U) apical loop
      of which the first and the fourth loop residues form a CG pair and the fifth loop
      residue is bulged out, as observed in the NMR structure. The model for the 23
      nucleotide SLbeta contains a 7-base-pair stem and a 9-nucleotide loop. Comparison
      of the models with other RNA structural elements, as well as similarity searches
      of human transcriptome and viral genomes demonstrate that SLalpha and SLbeta are
      specific to HBV transcripts. However, they are well conserved among the
      hepadnaviruses of non-human primates, the woodchuck and ground squirrel.

PMID- 27031750
TI  - Raman Analysis of Dilute Aqueous Samples by Localized Evaporation of
      Submicroliter Droplets on the Tips of Superhydrophobic Copper Wires.
AB  - Raman analysis of dilute aqueous solutions is normally prevented by their low
      signal levels. A very general method to increase the concentration to detectable
      levels is to evaporate droplets of the sample to dryness, creating solid deposits
      which are then Raman probed. Here, superhydrophobic (SHP) wires with hydrophilic
      tips have been used as supports for drying droplets, which have the advantage
      that the residue is automatically deposited at the tip. The SHP wires were
      readily prepared in minutes using electroless galvanic deposition of Ag onto
      copper wires followed by modification with a polyfluorothiol
      (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol, HDFT).
      Cutting the coated wires with a scalpel revealed hydrophilic tips which could
      support droplets whose maximum size was determined by the wire diameter.
      Typically, 230 MUm wires were used to support 0.6 MUL droplets. Evaporation of
      dilute melamine droplets gave solid deposits which could be observed by scanning
      electron microscopy (SEM) and Raman spectroscopy. The limit of detection for
      melamine using a two stage evaporation procedure was 1 * 10(-6) mol dm(-3). The
      physical appearance of dried droplets of sucrose and glucose showed that the
      samples retained significant amounts of water, even under high vacuum.
      Nonetheless, the Raman detection limits of sucrose and glucose were 5 * 10(-4)
      and 2.5 * 10(-3) mol dm(-3), respectively, which is similar to the sensitivity
      reported for surface-enhanced Raman spectroscopy (SERS) detection of glucose. It
      was also possible to quantify the two sugars in mixtures at concentrations which
      were similar to those found in human blood through multivariate analysis. 

PMID- 27031764
TI  - Characterization of decavanadate and decaniobate solutions by Raman spectroscopy.
AB  - The decaniobate ion, (Nb10 = [Nb10O28](6-)) being isoelectronic and isostructural
      with the decavanadate ion (V10 = [V10O28](6-)), but chemically and
      electrochemically more inert, has been useful in advancing the understanding of
      V10 toxicology and pharmacological activities. In the present study, the solution
      chemistry of Nb10 and V10 between pH 4 and 12 is studied by Raman spectroscopy.
      The Raman spectra of V10 show that this vanadate species dominates up to pH 6.45
      whereas it remains detectable until pH 8.59, which is an important range for
      biochemistry. Similarly, Nb10 is present between pH 5.49 and 9.90 and this
      species remains detectable in solution up to pH 10.80. V10 dissociates at most pH
      values into smaller tetrahedral vanadate oligomers such as V1 and V2, whereas
      Nb10 dissociates into Nb6 under mildly (10 > pH > 7.6) or highly alkaline
      conditions. Solutions of V10 and Nb10 are both kinetically stable under basic pH
      conditions for at least two weeks and at moderate temperature. The Raman method
      provides a means of establishing speciation in the difficult niobate system and
      these findings have important consequences for toxicology activities and
      pharmacological applications of vanadate and niobate polyoxometalates.

PMID- 27031765
TI  - Increased Pelvic Incidence is Associated With a More Coronal Facet Orientation in
      the Lower Lumbar Spine: A Cadaveric Study of 599 Lumbar Spines.
AB  - STUDY DESIGN: An anatomic study of facet angle orientation and morphology of the
      lumbar spine was performed. OBJECTIVE: The aim of this study was to determine how
      age, gender, race, and pelvic incidence (PI) correlate with facet orientation in
      the lumbar spine. SUMMARY OF BACKGROUND DATA: Lumbar facet orientation has
      important implications in the development of numerous pathologies of the spine,
      including arthritis, spondylolisthesis, and adult spinal deformity. Preliminary
      reports have suggested that sagittal balance of the spine may contribute to facet
      joint orientation. We therefore designed an anatomic study to investigate the
      relationship between PI and facet orientation, within the context of age, gender,
      and race. METHODS: Five hundred ninety-nine cadaveric lumbar spines were obtained
      from the Hamann-Todd osteological collection. It was determined that facet angle
      was most reliably assessed by measuring the angle between the superior articular
      facet and the spinous process. Facet angles were measured bilaterally at each
      level from T12-L1 through L5-S1 in every specimen. Multivariate regression
      analysis was used to determine independent predictors of facet angle at each
      level. RESULTS: Facet angle increased rostrally to caudally, from 22.6 +/- 8.3
      degrees  at T12-L1 to 49.1 +/- 12.4 degrees  at L5-S1. Cadaver age was an
      independent predictor of a more sagittal facet angle at lower spinal levels.
      Caucasian race was an independent predictor of increasing facet angle. Increased
      PI had no effect on facet angle at T12-L1, L1-L2, L2-L3, or L3-L4, although was a
      significant predictor of more coronally oriented facet joints at L4-L5
      (standardized beta 0.096, P = 0.009) and L5-S1 (standardized beta 0.079, P =
      0.032). CONCLUSION: The results of this study provide important data regarding
      differences in facet angle that exists between individuals. Moreover, the results
      of this study suggest that facet joints do possess the ability to remodel over
      time, perhaps in response to perturbations of sagittal balance, osteophyte
      formation, or other yet to be determined factors. LEVEL OF EVIDENCE: N/A.

PMID- 27031766
TI  - Preoperative T1 Slope More Than 40 degrees  as a Risk Factor of Correction Loss
      in Patients With Adult Spinal Deformity.
AB  - STUDY DESIGN: A retrospective study of surgical outcomes of adult spinal
      deformity (ASD) cases. OBJECTIVE: The aim of the study was to investigate the
      effects of high T1 slope (T1S) on surgical outcomes in patients with ASD. SUMMARY
      OF BACKGROUND DATA: Few studies have evaluated the surgical outcomes of patients
      with ASD with cervical deformities. METHODS: Eighty-eight patients with ASD who
      underwent posterior spinal corrective fusion were assigned to either group A (T1S
      <40 degrees ) or group B (T1S >=40 degrees ). Whole-spine standing radiographs of
      both groups were preoperatively assessed: at first standing after the surgery and
      at 1 and 2 years postoperatively. RESULTS: There were 56 patients in group A and
      32 in group B. The preoperative C7 sagittal vertical axis (SVA) improved from 61
      to 41 mm in group A and from 161 to 64 mm in group B at first standing after the
      surgery. C7 SVA at 2 years after the surgery was, however, 57 mm in group A and
      98 mm in group B because of correction loss (P = 0.003). T1S measurements before
      and immediately after the surgery and 2 years after the surgery were, however, 25
      degrees , 23 degrees , and 27 degrees  in group A and 53 degrees , 36 degrees ,
      and 41 degrees  in group B, respectively. There were no significant differences
      among measurements in group A. Those in group B were, however, significantly
      improved in the first standing, but T1S of 40 degrees  or higher deteriorated
      toward 2 years after the surgery. CONCLUSION: Among patients with T1S of 40
      degrees  or higher, C7 SVA improved immediately after the surgery but worsened at
      2 years after the surgery. These results suggested that cervicothoracic
      parameters were important predictors of correction loss. LEVEL OF EVIDENCE: 4.

PMID- 27031767
TI  - Dumbbell Scoring System: A New Method for the Differential Diagnosis of Malignant
      and Benign Spinal Dumbbell Tumors.
AB  - STUDY DESIGN: Retrospective diagnostic analysis. OBJECTIVE: The aim of the study
      was to establish a new scoring system, the dumbbell scoring system (DSS), for
      preoperative evaluation of the malignant potential of spinal dumbbell tumors
      (SDTs). SUMMARY OF BACKGROUND DATA: Among SDTs, benign tumors such as schwannomas
      occur frequently, whereas malignant SDTs, including malignant peripheral nerve
      sheath tumors, are uncommon. No scoring system has been developed to
      preoperatively diagnose the malignant potential of SDTs. METHODS: We
      retrospectively reviewed the records of 59 consecutive patients with SDTs. The
      following imaging features were recorded: tumor size, tumor shape, tumor
      boundary, pattern of enhancement of intratumoral lesions (homogeneous or
      heterogeneous), cyst formation in the tumors on magnetic resonance imaging, and
      enlargement of neural foramina and scalloping or osteolytic destruction of
      surrounding bones on computed tomography. The prevalence of characteristic
      imaging features in malignant and benign SDTs were evaluated, and appropriate cut
      off points for the DSS score were obtained using receiver operating
      characteristics. RESULTS: Twenty cases were confirmed to be malignant tumors.
      Pathological diagnoses of the malignant SDTs were as follows: 11 cases of
      malignant peripheral nerve sheath tumor; 3 cases of malignant lymphoma; and 1
      case each of extraskeletal Ewing sarcoma, hemangiopericytoma,
      hemangioendothelioma, malignant myoepithelioma, neuroblastoma, and plasmacytoma.
      The DSS was based on four characteristic imaging features confirmed as
      significant predictors of malignant SDTs, namely, maximal diameter greater than 5
      cm, irregularly lobulated tumor, tumor boundary indistinguishable from
      surrounding tissues, and osteolytic bone destruction. Malignant SDTs showed a
      higher DSS score (median 5.5 points) than did benign SDTs (median 0 point). The
      optimum cut-off value for the DSS score was 3 points, and the sensitivity and
      specificity for the diagnosis of malignant SDTs were 90% and 84.6%, respectively.
      CONCLUSION: This scoring system may be helpful for preoperative decision making.
      If the DSS score is equal to or higher than 3, biopsies was recommended to
      confirm the histological diagnosis. LEVEL OF EVIDENCE: 4.

PMID- 27031768
TI  - Reoperation Rates After Surgery for Degenerative Cervical Spine Disease According
      to Different Surgical Procedures: National Population-based Cohort Study.
AB  - STUDY DESIGN: National population-based cohort study. OBJECTIVE: To evaluate
      reoperation rates of cervical spine surgery for cervical degenerative conditions
      utilizing a national population database. SUMMARY OF BACKGROUND DATA: There is an
      inherently low incidence of reoperation after surgery for cervical degenerative
      disease. Therefore, it is difficult to sufficiently power studies to detect
      differences between reoperation rates of different cervical surgical procedures.
      National population-based databases provide large, longitudinally followed
      cohorts that may help overcome this challenge. METHODS: We used the Korean Health
      Insurance Review and Assessment Service national database to select our study
      population. We included patients with diagnosis of cervical spondylotic
      radiculopathy or myelopathy who underwent cervical surgeries from January 2009 to
      June 2014. We separated patients into three groups based on surgical procedures:
      discectomy or corpectomy with anterior fusion, laminoplasty, or laminectomy with
      posterior fusion. Age, sex, presence of diabetes, osteoporosis, associated
      comorbidities, number of operated cervical disc levels, and hospital types were
      considered potential confounding factors. Reoperation rates were analyzed over
      early and late periods. RESULTS: The reoperation rate over the entire follow-up
      period was 3.31%. Overall, the reoperation rate was significantly higher after
      laminectomy with posterior fusion or laminoplasty than after discectomy or
      corpectomy with anterior fusion. A similar pattern was seen during the late
      period. In the early period, rates were higher only after laminectomy with
      posterior fusion than after discectomy or corpectomy with anterior fusion. Sex,
      presence of diabetes, associated comorbidities, and hospital types were noted to
      be risk factors for reoperation. CONCLUSION: The reoperation rate was higher
      after laminectomy with posterior fusion or laminoplasty. Given clinical scenarios
      in which either anterior or posterior approaches can be utilized, risk of
      reoperation can be another variable to consider in surgical planning and patient
      education. LEVEL OF EVIDENCE: 3.

PMID- 27031769
TI  - The Economic Implications of an Incidental Durotomy.
AB  - STUDY DESIGN: Case-control. OBJECTIVE: The aim of this study was to determine the
      economic impact of an incidental durotomy in spine surgery. SUMMARY OF BACKGROUND
      DATA: An incidental durotomy during spine surgery does not affect long-term
      outcomes, but as reimbursement moves toward bundled payments, it may
      substantially affect the profitability of spine surgery. METHODS: A retrospective
      review of a prospectively collected morbidity and mortality database identified
      all patients with an incidental durotomy between January 1, 2012, and January 11,
      2013. Subjects with a dural tear were matched to controls (1 : 2) without a dural
      tear, and the total charges for one year were collected. Controls were required
      to meet the following criteria: Age +/-5 years; Charlson Comorbidity Index (CCI)
      +/-1; Date of surgery +/-2 years; Exact region of the spine, but not the exact
      level (i.e., lumbar -> lumbar); Exact type of fusion (i.e., approach,
      instrumentation); Exact number of levels fused; Use of rhBMP-2; Number of levels
      decompressed +/-1. RESULTS: Two controls without a dural tear could be identified
      for 57 patients who sustained an incidental durotomy. No difference in
      demographic data, emergency room visits, hospital readmissions, or revision
      surgeries between the groups was identified. Patients with an incidental durotomy
      had a longer operative time by 30.6 +/- 8.5 minutes (P < 0.01), longer length of
      stay by 0.89 +/- 0.27 days (P = 0.0001), and an increase in their average initial
      hospital charge by 18%. No increase in surgeon-based charges or hospital-based
      charges after the initial visit was identified. CONCLUSION: An incidental
      durotomy significantly increases the initial hospital charges for patients
      undergoing spine surgery; however, in this study it has no effect on surgeon
      based charges or on hospital-based charges after discharge. LEVEL OF EVIDENCE: 3.

PMID- 27031770
TI  - Postoperative Paralysis From Thoracic Ossification of Posterior Longitudinal
      Ligament Surgery Risk Factor of Neurologic Injury: Nationwide Multiinstitution
      Survey.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: The purpose of this
      study was to examine the factors of postoperative paralysis in patients who have
      undergone thoracic ossification of posterior longitudinal ligament (OPLL)
      surgery. SUMMARY OF BACKGROUND DATA: A higher percentage of thoracic OPLL
      patients experience postoperative aggravation of paralysis than cervical OPLL
      patients, including patients that presented great difficulties in treatment.
      However, there were a few reports to prevent paralysis thoracic OPLL. METHODS:
      The 156 patients who had received thoracic OPLL surgery were selected as the
      subjects of this study. The items for review were the duration of disease; the
      preoperative muscle strength (Muscle Manual Testing); OPLL levels (T1/2-4/5:
      high, T5/6-8/9: middle, and T9/10-11/12: low); the spinal canal occupancy ratio;
      the ratio of yellow ligament ossification as a complication; the ratio of
      transcranial-motor evoked potential (Tc-MEP) derivation; the
      preoperative/postoperative kyphotic angles in the thoracic vertebrae; the
      correction angle of kyphosis; the duration of surgery; and the amount of
      bleeding. The subjects were divided into two groups based on the absence or
      presence of postoperative paralysis to determine the factors of postoperative
      paralysis. RESULTS: Twenty-three patients (14.7%) exhibited postoperative
      paralysis. Multivariate analysis identified factors associated with postoperative
      paralysis: the duration of disease (odds ratio, OR = 3.3); the correction angle
      of kyphosis (OR = 2.4); and the ratio of Tc-MEP derivation (OR = 2.2).
      CONCLUSION: The risk factors of postoperative paralysis are a short duration of
      disease and a small correction angle of kyphosis. In addition, ratios of Tc-MEP
      derivation below 50% may anticipate paralysis. LEVEL OF EVIDENCE: 4.

PMID- 27031771
TI  - To the Editor.

PMID- 27031772
TI  - Meta-analysis of the Impact of Patient Characteristics on Estimates of
      Effectiveness and Harms of Recombinant Human Bone Morphogenetic Protein-2 in
      Lumbar Spinal Fusion.
AB  - STUDY DESIGN: Meta-analysis of individual patient data from randomized controlled
      trials of recombinant human bone morphogenetic protein-2 (rhBMP-2) in lumbar
      spinal fusion. OBJECTIVE: To determine how patient characteristics impact
      estimates of effectiveness and harms of rhBMP-2 versus iliac crest bone graft
      (ICBG) in lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Patient
      characteristics are thought to impact rates of fusion in spinal fusion surgery,
      but no analyses examining the effect of patient characteristics on efficacy and
      safety of rhBMP-2 as compared with ICBG have been conducted. METHODS: Using
      individual patient data obtained from the Yale Open Data Access Project, the
      impact of patient characteristics on the effects of rhBMP-2 on fusion, overall
      success, and harms were assessed using linear and generalized linear mixed
      effects models. RESULTS: Ten industry-sponsored randomized controlled trials of
      rhBMP-2 were included in the analysis. There is preliminary support for an
      association between rhBMP-2 and improved outcomes for smokers (P = 0.01),
      individuals under the age of 60 years (P < 0.01), and patients of normal weight
      (P = 0.03), but not in patients who are nonsmokers, over the age of 60 years,
      obese or severely obese. RhBMP-2 usage was associated with decreased harms in
      individuals with no previous back surgeries but this was not seen in individuals
      with a previous back surgery (P < 0.01). CONCLUSION: Effects of rhBMP-2 may vary
      according to patient characteristics. Future studies of rhBMP-2 should include
      planned subgroup analysis in patients over 60 years, smokers, patients that are
      obese and severely obese, and individuals with previous back surgeries to better
      identify those most likely to benefit. LEVEL OF EVIDENCE: 1.

PMID- 27031773
TI  - Incidence and Risk Factors for 30-Day Unplanned Readmissions After Elective
      Posterior Lumbar Fusion.
AB  - STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To
      perform a multiinstitutional assessment on the incidence and risk factors for
      unplanned readmissions following elective posterior lumbar fusion (PLF) surgery.
      SUMMARY OF BACKGROUND DATA: Understanding what may drive rehospitalizations is a
      necessary step toward higher quality care. Identifying risk factors for unplanned
      readmission is especially important for elective PLF, which is a common procedure
      that is known to be associated with significant adverse events. METHODS: Adult
      patients undergoing PLF were identified using current procedure terminology (CPT)
      from the American College of Surgeons National Surgical Quality Improvement
      Program. Both descriptive and comparative statistics were performed for patient
      characteristics, clinical factors, and postoperative complications. Subsequently,
      a step-wise multivariate logistic regression was employed. RESULTS: Of the 2301
      patients who met inclusion criteria for this study, 117 were unplanned
      readmissions (5.1%). These occurred at a mean of 15.9 days (range: 3-30 days)
      after surgery. The risk-adjusted analysis revealed that bleeding disorder (odds
      ratio, OR = 2.8, confidence intervals, CI = 1.0-7.6, P = 0.043), insulin
      dependent diabetes (OR = 2.5, CI = 1.4-4.4, P = 0.004), and total length of stay
      > 5 days (OR = 1.8, CI = 1.2-2.8, P = 0.009) were independent predictors for
      unplanned readmission. Significant postoperative complications included wound
      complications (OR = 27.6, CI = 13.9-54.8, P < 0.0001), pulmonary embolism and/or
      deep vein thrombosis/thrombophlebitis (OR = 11.9, CI = 5.0-28.5, P < 0.0001),
      sepsis (OR = 8.5, CI = 2.3-32.1, P = 0.002), and urinary tract infections (OR =
      2.4, CI = 0.9-6.9, P = 0.094). CONCLUSION: The unplanned readmission rate for
      patients undergoing PLF was low, but this study's findings of potentially
      modifiable risk factors suggest that substantial improvement with this quality
      metric is possible. LEVEL OF EVIDENCE: N/A.

PMID- 27031774
TI  - Scratching the Surface of Suicide in Head and Neck Cancer-Reply.

PMID- 27031775
TI  - Automated Extraction of Formalin-Fixed, Paraffin-Embedded Tissue for High-Risk
      Human Papillomavirus Testing of Head and Neck Squamous Cell Carcinomas Using the
      Roche Cobas 4800 System.
AB  - CONTEXT: -Testing for high-risk human papillomavirus (HR-HPV) in head and neck
      squamous cell carcinomas (HNSCCs) is important for both prognostication and
      clinical management. Several testing platforms are available for HR-HPV; however,
      effective alternative automated approaches are needed. OBJECTIVE: -To assess the
      performance of the automated Roche cobas 4800 HPV real-time polymerase chain
      reaction-based system on formalin-fixed, paraffin-embedded HNSCC specimens and
      compare results with standard methods of in situ hybridization (ISH) and p16
      immunohistochemistry. DESIGN: -Formalin-fixed, paraffin-embedded samples of HNSCC
      were collected from archival specimens in the Department of Pathology,
      Massachusetts General Hospital (Boston), and prepared using the automated system
      by deparaffinization and dehydration followed by tissue lysis. Samples were
      integrated into routine cervical cytology testing runs by cobas. Corresponding
      formalin-fixed, paraffin-embedded samples were evaluated for HR-HPV by ISH and
      p16 by immunohistochemistry. Discrepant cases were adjudicated by polymerase
      chain reaction. RESULTS: -Sixty-two HNSCC samples were analyzed using the
      automated cobas system, ISH, and immunohistochemistry. Fifty-two percent (n = 32
      of 62) of formalin-fixed, paraffin-embedded tumors were positive for HR-HPV by
      cobas. Eighty-eight percent (n = 28 of 32) of cases were the HPV 16 subtype and
      12% (n = 4 of 32) were other HR-HPV subtypes. Corresponding testing with ISH was
      concordant in 92% (n = 57 of 62) of cases. Compared with the adjudication
      polymerase chain reaction standard, there were 3 false-positive cases by cobas.
      CONCLUSIONS: -Concordance in HNSCC HR-HPV status between cobas and ISH was more
      than 90%. The cobas demonstrated a sensitivity of 100% and a specificity of 91%
      for detection of HR-HPV. Advantages favoring cobas include its automation, cost
      efficiency, objective results, and ease of performance.

PMID- 27031776
TI  - Sarcomatoid Urothelial Carcinoma of the Bladder: Analysis of 28 Cases With
      Emphasis on Clinicopathologic Features and Markers of Epithelial-to-Mesenchymal
      Transition.
AB  - CONTEXT: -Sarcomatoid urothelial carcinoma (UCa) is a rare but aggressive variant
      of bladder cancer that can show diagnostic challenges even using ancillary
      techniques. OBJECTIVE: -To examine immunohistochemical markers in the context of
      sarcomatoid UCa, including those associated with epithelial-to-mesenchymal
      transition. DESIGN: -Twenty-eight cases of sarcomatoid UCa were rereviewed.
      Clinical outcomes were obtained through database search. Immunohistochemistry for
      clinical and epithelial-to-mesenchymal transition markers was performed. RESULTS:
      -All patients had biopsy-proven invasive UCa; 61% (17 of 28) had sarcomatoid UCa
      at initial diagnosis. A recognizable epithelial component(s) was present in 17
      lesions. The sarcomatoid component accounted for 65% of the lesion (average),
      with heterologous elements present in 3 of 28 cases (11%). The morphologic
      spectrum of the sarcomatoid element included spindled not otherwise specified,
      myxoid, pseudoangiosarcomatous, and malignant fibrous histiocytoma-like
      undifferentiated features. The sarcomatoid component was immunoreactive for
      pancytokeratin (22 of 26; 85%), p63 (20 of 26; 77%), cytokeratin 903 (17 of 26;
      65%), cytokeratin 7 (16 of 26; 62%), GATA3 (16 of 26; 62%), and cytokeratin 5/6
      (16 of 26; 62%). STAT-6, CD31, CD34, and HMB45 were all nonreactive, whereas
      smooth muscle actin often showed at least focal immunoreactivity (22 of 26; 85%).
      Epithelial-to-mesenchymal transition markers were frequently expressed, including
      vimentin (26 of 26; 100%), FoxC2 (26 of 26; 100%), SNAIL (23 of 26; 88.5%), and
      ZEB1 (18 of 26; 69.2%). Follow-up was available for 24 patients (median, 7
      months). Sixteen of 28 patients (57%) died of disease (overall mean survival, 9.1
      months). The presence of myxoid or chordoid features was associated with reduced
      survival (P < .05). CONCLUSIONS: -Sarcomatoid UCa is an aggressive form of UCa
      that frequently expresses epithelial-to-mesenchymal transition markers,
      suggesting a possible mechanism associated with aggressive tumor behavior.

PMID- 27031778
TI  - An Intraoral Mass Associated With Myelodysplastic Syndrome.

PMID- 27031777
TI  - Dataset for Reporting of Malignant Mesothelioma of the Pleura or Peritoneum:
      Recommendations From the International Collaboration on Cancer Reporting (ICCR).
AB  - CONTEXT: -The International Collaboration on Cancer Reporting is a not-for-profit
      organization formed by the Royal Colleges of Pathologists of Australasia and the
      United Kingdom; the College of American Pathologists; the Canadian Association of
      Pathologists-Association Canadienne des Pathologists, in association with the
      Canadian Partnership Against Cancer; and the European Society of Pathology. Its
      goal is to produce common, internationally agreed upon, evidence-based datasets
      for use throughout the world. OBJECTIVE: -To describe a dataset developed by the
      Expert Panel of the International Collaboration on Cancer Reporting for reporting
      malignant mesothelioma of both the pleura and peritoneum. The dataset is composed
      of "required" (mandatory) and "recommended" (nonmandatory) elements. DESIGN: 
      Based on a review of the most recent evidence and supported by explanatory
      commentary. RESULTS: -Eight required elements and 7 recommended elements were
      agreed upon by the Expert Panel to represent the essential information for
      reporting malignant mesothelioma of the pleura and peritoneum. CONCLUSIONS: -In
      time, the widespread use of an internationally agreed upon, structured, pathology
      dataset for mesothelioma will lead not only to improved patient management but
      also provide valuable data for research and international benchmarks.

PMID- 27031781
TI  - Difficult safety problems.

PMID- 27031782
TI  - Assessing trends over time.

PMID- 27031783
TI  - Operando Measurement of Solid Electrolyte Interphase Formation at Working
      Electrode of Li-Ion Battery by Time-Slicing Neutron Reflectometry.
AB  - We report the first operando measurement of solid electrolyte interphase (SEI)
      formation at an electrode using in situ neutron reflectometry. The results
      revealed the growth of the SEI and intercalation of ions during the charge
      reaction. Furthermore, we propose a way of evaluating the charge used for the SEI
      formation. 

PMID- 27031784
TI  - Association of blood groups with ovarian reserve and outcome of in vitro
      fertilization treatment.
AB  - BACKGROUND: The association between ABO blood groups and ovarian reserve in
      infertile patients has been a point of controversy. OBJECTIVES: The aim of this
      study was to assess the correlation of certain blood groups with ovarian reserve
      and response to treatment in patients undergoing infertility treatment. DESIGN:
      Retrospective medical record review. SETTING: Infertility clinic in the assisted
      reproductive technology (ART) unit at King Faisal Specialist Hospital and
      Research Center, Riyadh Saudi Arabia. PATIENTS AND METHODS: All patients under 40
      years of age who attended the infertility clinic at a tertiary care centre in
      2010 and underwent in vitro fertilization (IVF) treatment in 2010 and 2011 were
      divided into groups according to blood type, and clinical parameters were
      compared. MAIN OUTCOME MEASURE(S): The association between blood groups and
      ovarian reserve using day 3 luteinzing hormone (LH) and follicular stimulating
      hormone (FSH) levels, and antral follical count (AFC). RESULTS: In 424 patients
      who underwent 566 IVF cycles, age, LH, FSH and AFC were similar among the
      different blood groups (P=.9, .1, .5, respectively). with controlled ovarian
      stimulation, no difference was observed among the four groups in menopausal
      gonadotrophin (hMG) dose or the duration of stimulation. The number of oocytes
      retrieved, fertilization rate, cleavage rate, and number of embryos transferred
      were similar. There was no difference in the cancellation rate or pregnancy rate
      among the groups. CONCLUSION: There was no significant association between blood
      type and ovarian reserve or response during IVF treatment in our population.
      LIMITATIONS: Anti-Mullerian hormone levels are best correlated with ovarian
      reserve testing. Unavailability of AMH levels. Retrospective design.

PMID- 27031785
TI  - Crawling towards a map of the brain.
AB  - State-of-the-art techniques reveal a simple circuit of neurons controls the
      muscle contractions that allow fruit fly larvae to crawl.

PMID- 27031786
TI  - Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D
      Tumor Platform.
AB  - Overcoming transport barriers to delivery of therapeutic agents in tumors remains
      a major challenge. Focused ultrasound (FUS), in combination with modern
      nanomedicine drug formulations, offers the ability to maximize drug transport to
      tumor tissue while minimizing toxicity to normal tissue. This potential remains
      unfulfilled due to the limitations of current approaches in accurately assessing
      and quantifying how FUS modulates drug transport in solid tumors. A novel
      acoustofluidic platform is developed by integrating a physiologically relevant 3D
      microfluidic device and a FUS system with a closed-loop controller to study drug
      transport and assess the response of cancer cells to chemotherapy in real time
      using live cell microscopy. FUS-induced heating triggers local release of the
      chemotherapeutic agent doxorubicin from a liposomal carrier and results in higher
      cellular drug uptake in the FUS focal region. This differential drug uptake
      induces locally confined DNA damage and glioblastoma cell death in the 3D
      environment. The capabilities of acoustofluidics for accurate control of drug
      release and monitoring of localized cell response are demonstrated in a 3D in
      vitro tumor mode. This has important implications for developing novel strategies
      to deliver therapeutic agents directly to the tumor tissue while sparing healthy
      tissue.

PMID- 27031787
TI  - A Stromal Cell-Derived Factor 1alpha Analogue Improves Endothelial Cell Function
      in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.
AB  - Endothelial cell (EC) dysfunction is a critical mediator of the acute respiratory
      distress syndrome (ARDS). Recent studies have demonstrated that stromal cell
      derived factor 1alpha (SDF-1alpha) promotes EC barrier integrity. Our previous
      studies used a SDF-1alpha analogue CTCE-0214 (CTCE) in experimental sepsis and
      demonstrated that it attenuated vascular leak and modulated microRNA (miR)
      levels. We examined the hypothesis that CTCE improves EC function in
      lipopolysaccharide (LPS)-induced ARDS through increasing miR-126 expression.
      Human microvascular endothelial cells (HMVECs) were treated with thrombin to
      disrupt the EC integrity followed by incubation with CTCE or SDF-1alpha. Barrier
      function was determined by trans-endothelial electrical resistance assay. CTCE
      induced alterations in miRNA expression and signaling pathways involved in
      barrier function were determined. Thrombin-induced vascular leak was abrogated by
      both CTCE and SDF-1alpha. CTCE also prevented thrombin-induced decreases of
      vascular endothelial (VE)-cadherin cell surface expression and expansion of the
      intercellular space. CTCE increased miR-126 levels and induced activation of
      AKT/Rac 1 signaling. Cotreatment with a miR-126 inhibitor blocked the protective
      effects of CTCE on AKT activation and endothelial permeability. In subsequent in
      vivo studies, ARDS was induced by intratracheal instillation of LPS. Intravenous
      injection of CTCE diminished the injury severity as evidenced by significant
      reductions in protein, immune cells, inflammatory cytokines and chemokines in the
      bronchoalveolar lavage fluid, increased miR-126 expression and decreased
      pulmonary vascular leak and alveolar edema. Taken together, our data show that
      CTCE improves endothelial barrier integrity through increased expression of miR
      126 and activation of Rac 1 signaling and represents an important potential
      therapeutic strategy in ARDS.

PMID- 27031788
TI  - On-Site Renewable Energy and Green Buildings: A System-Level Analysis.
AB  - Adopting a green building rating system (GBRSs) that strongly considers use of
      renewable energy can have important environmental consequences, particularly in
      developing countries. In this paper, we studied on-site renewable energy and
      GBRSs at the system level to explore potential benefits and challenges. While we
      have focused on GBRSs, the findings can offer additional insight for renewable
      incentives across sectors. An energy model was built for 25 sites to compute the
      potential solar and wind power production on-site and available within the
      building footprint and regional climate. A life-cycle approach and cost analysis
      were then completed to analyze the environmental and economic impacts.
      Environmental impacts of renewable energy varied dramatically between sites, in
      some cases, the environmental benefits were limited despite the significant
      economic burden of those renewable systems on-site and vice versa. Our
      recommendation for GBRSs, and broader policies and regulations, is to require
      buildings with higher environmental impacts to achieve higher levels of energy
      performance and on-site renewable energy utilization, instead of fixed
      percentages.

PMID- 27031789
TI  - Physician-Assisted Death Does Not Improve End-of-Life Care.

PMID- 27031790
TI  - Clinical 'Pearls' of maternal critical care: part I.
AB  - PURPOSE OF REVIEW: This review outlines the challenges in looking after pregnant
      women with thromboembolism and sepsis who either become or are at risk of
      becoming critically ill during pregnancy. RECENT FINDINGS: The Pregnancy
      Mortality Surveillance systems in both the USA and UK record the most common
      causes of maternal death as thromboembolism and sepsis. Both of these conditions
      have improved outcomes with timely maternal critical care provided by a
      multidisciplinary team. SUMMARY: In this review, we discuss the pathophysiology,
      diagnosis, and management of thromboembolism and sepsis, two very important
      conditions with high mortality requiring admission to intensive care.

PMID- 27031791
TI  - Obstetric early warning systems to prevent bad outcome.
AB  - PURPOSE OF REVIEW: Early warning scores, early warning systems and rapid response
      systems, were established in 1999. In the UK, a National Early Warning Score was
      launched in 2013 and is now used throughout the National Health Service. In 2007,
      a firm recommendation was made by the maternal confidential death enquiry that
      maternity units should incorporate a modified early obstetric warning score chart
      into clinical practice. Although there was enthusiastic uptake of this
      recommendation, local recording systems vary throughout the country and there is
      now a need to revisit revise and standardize an obstetric early warning system
      (ObsEWS). RECENT PROJECT: The intercollegiate Maternal Critical Care group of the
      Obstetric Anaesthetists' Association have produced an ObsEWS in line with the
      aggregate UK National Early Warning Score. Six physiological parameters are
      incorporated: respiratory rate, oxygen saturations, temperature, systolic blood
      pressure, diastolic blood pressure, and pulse rate. However, robust physiological
      thresholds for the measured parameters are currently lacking but required for a
      more sensitive and specific ObsEWS. SUMMARY: A greater focus and study on the
      management of maternal morbidity (in addition to mortality data) and the
      development of better systems within and across the multidisciplinary team to
      detect early deterioration should improve management of serious illness in
      obstetrics. It is imperative that we undertake robust ObsEWS and data collection,
      including electronic systems with research and evidence-based recommendations to
      underpin this system. This should improve patient safety and result in more
      efficient, cost-effective management of sicker patients in our complex modern
      healthcare systems.

PMID- 27031793
TI  - Reply to Cantrell and Nordt.

PMID- 27031792
TI  - The patient with hypertension undergoing surgery.
AB  - PURPOSE OF REVIEW: General recommendations for the perioperative management of
      patients with hypertensive disease have not evolved much over the past 20 years,
      yet new pathophysiological concepts have emerged and new monitoring techniques
      are available today. In this review, we will discuss their significance and
      potential role in the modern perioperative care of hypertensive patients. RECENT
      FINDINGS: For hypertensive patients, total cardiovascular risk rather than blood
      pressure (BP) alone should determine the preoperative strategy. Except for grade
      3 hypertension, surgery should not be deferred on the basis of an elevated BP in
      the preoperative assessment.New data suggest that even brief hypotensive episodes
      during surgery may have significant impact on outcome. Isolated systolic
      hypertension is the predominant phenotype in elderly patients who may be
      particularly vulnerable to hypoperfusion in the perioperative setting.New
      monitoring techniques such as echocardiography and near-infrared spectroscopy may
      provide crucial information to optimize intraoperative control of BP based on an
      individual patient's pathophysiology. SUMMARY: Hypertension is highly prevalent
      in patients presenting for surgery yet its impact on surgical outcome is still
      debated. Guidelines on risk stratification and perioperative hemodynamic
      management of patients with hypertensive disease remain sparse and cannot rely
      much on solid new evidence. Target organ damage associated with hypertensive
      disease rather than high BP per se appears to determine perioperative risk. In
      the absence of new data, an individualized and pathophysiology-based approach to
      control BP may be the best option to guide these patients through the
      perioperative period.

PMID- 27031794
TI  - Reduced density matrix embedding. General formalism and inter-domain correlation
      functional.
AB  - An embedding method for a one-electron reduced density matrix (1-RDM) is
      proposed. It is based on partitioning of 1-RDM into domains and describing each
      domain in the effective potential of the other ones. To assure N-representability
      of the total 1-RDM N-representability and strong-orthogonality conditions are
      imposed on the domains. The total energy is given as a sum of single-domain
      energies and domain-domain electron interaction contributions. Higher than two
      body inter-domain interaction terms are neglected. The two-body correlation terms
      are approximated by deriving inter-domain correlation from couplings of density
      fluctuations of two domains at a time. Unlike in most density embedding methods
      kinetic energy is treated exactly and it is not required that densities
      pertaining to the domains are only weakly overlapping. We propose to treat each
      domain by a corrected perfect-pairing functional. On a few examples it is shown
      that the embedding reduced density matrix functional method (ERDMF) yields
      excellent results for molecules that are well described by a single Lewis
      structure even if strong static intra-domain or dynamic inter-domain correlation
      effects must be accounted for. 

PMID- 27031795
TI  - Parental stress among parents of toddlers with moderate hearing loss.
AB  - BACKGROUND: The purpose of this study was to examine parental stress in parents
      of toddlers with moderate hearing loss compared to hearing controls. Furthermore,
      the associations between parental stress and child- and parent-related factors
      such as language, social-emotional functioning and social support were examined.
      DESIGN: The study sample consisted of 30 toddlers with moderate hearing loss and
      30 hearing children (mean age 27.4 months). The two groups were compared using
      the Nijmegen Parenting Stress Index (NPSI) and parent-reports to rate the amount
      of social support and the children's social-emotional functioning. Receptive and
      expressive language tests were administered to the children to examine their
      language ability. RESULTS: Parents of toddlers with moderate hearing loss
      reported comparable levels of parental stress to parents of hearing children.
      Individual differences in parental stress were related to child- and parent
      related factors. Poorer social-emotional functioning and language ability of the
      child were related to higher stress levels in parents. Parents who experienced
      less social support reported higher stress levels. CONCLUSIONS: Parents of
      toddlers with moderate hearing loss experience no more parental stress than
      parents of hearing children on average. Given parental stress was found to be
      related to poorer child functioning, early interventionists should be aware of
      signs of elevated stress levels in parents.

PMID- 27031796
TI  - An approach to "escape from flatland": chemo-enzymatic synthesis and biological
      profiling of a library of bridged bicyclic compounds.
AB  - A major reason for the low success rate in current drug development through
      chemical synthesis has been ascribed to the large fraction of quasi planar
      candidate molecules. Therefore, an "escape from flatland" strategy has been
      recommended for the generation of bioactive chemical entities. In a first attempt
      to test this recommendation, we synthesized a small collection of bridged
      bicyclic compounds possessing a rigid spherical core structure by combining a
      group of cyclic dienes with a collection of dienophiles. We started from planar
      biphenyl analogues and, by enzymatic dioxygenation, transformed them into
      hydroxylated diene structures. Using a small library of newly synthesized
      dienophiles, the dienes were converted into bridged bicycles via the Diels-Alder
      reaction. The resulting collection of 78 structures was first tested for
      bioactivity in a generic assay based on interference with the proliferation of
      mammalian cells. A more mechanism-targeted bioactivity profiling method,
      exploiting cellular impedance monitoring, was subsequently used to obtain
      suggestions for the mode of action exerted by those compounds that were the most
      active in the proliferation assay. Proteasome inhibition could be confirmed for 8
      of a series of 9 respective candidates. Whilst 7 of these molecules showed
      relatively weak interference with proteasome activity, one candidate exerted a
      moderate but distinct inhibition. This result appears remarkable in view of the
      small size of the compound library, which was synthesized following a few basic
      considerations. It encourages the application of diverse synthetic approaches to
      further investigate the role of spherical shape for the success of compound
      libraries. 

PMID- 27031797
TI  - Preclinical pharmacokinetics of MHAA4549A, a human monoclonal antibody to
      influenza A virus, and the prediction of its efficacious clinical dose for the
      treatment of patients hospitalized with influenza A.
AB  - MHAA4549A is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds to a
      highly conserved epitope on the stalk of influenza A hemagglutinin and blocks the
      hemagglutinin-mediated membrane fusion in the endosome, neutralizing all known
      human influenza A strains. Pharmacokinetics (PK) of MHAA4549A and its related
      antibodies were determined in DBA/2J and Balb-c mice at 5 mg/kg and in cynomolgus
      monkeys at 5 and 100 mg/kg as a single intravenous dose. Serum samples were
      analyzed for antibody concentrations using an ELISA and the PK was evaluated
      using WinNonlin software. Human PK profiles were projected based on the PK in
      monkeys using species-invariant time method. The human efficacious dose
      projection was based on in vivo nonclinical pharmacological active doses,
      exposure in mouse infection models and expected human PK. The PK profiles of
      MHAA4549A and its related antibody showed a linear bi-exponential disposition in
      mice and cynomolgus monkeys. In mice, clearance and half-life ranged from 5.77 to
      9.98 mL/day/kg and 10.2 to 5.76 days, respectively. In cynomolgus monkeys,
      clearance and half-life ranged from 4.33 to 4.34 mL/day/kg and 11.3 to 11.9 days,
      respectively. The predicted clearance in humans was ~2.60 mL/day/kg. A single
      intravenous dose ranging from 15 to 45 mg/kg was predicted to achieve efficacious
      exposure in humans. In conclusion, the PK of MHAA4549A was as expected for a
      human IgG1 monoclonal antibody that lacks known endogenous host targets. The
      predicted clearance and projected efficacious doses in humans for MHAA4549A have
      been verified in a Phase 1 study and Phase 2a study, respectively.

PMID- 27031798
TI  - Consensus statement on surgical pathology of the aorta from the Society for
      Cardiovascular Pathology and the Association For European Cardiovascular
      Pathology: II. Noninflammatory degenerative diseases - nomenclature and
      diagnostic criteria.
AB  - Surgical aortic specimens are usually examined in Pathology Departments as a
      result of treatment of aneurysms or dissections. A number of diseases, genetic
      syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging
      processes involved in vascular injury can cause both distinct and nonspecific
      histopathologic changes with degeneration of the media as a common denominator.
      Terminology for these changes has varied over time leading to confusion and
      inconsistencies. This consensus document has established a revised, unified
      nomenclature for the variety of noninflammatory degenerative aortic
      histopathologies seen in such specimens. Older terms such as cystic medial
      necrosis and medionecrosis are replaced by more technically accurate terms such
      as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation
      and/or loss, and smooth muscle cell nuclei loss. A straightforward system of
      grading is presented to gauge the extent of medial degeneration and synoptic
      reporting tables are provided. Herein we present a standardized nomenclature that
      is accessible to general pathologists and useful for future publications
      describing these entities. 

PMID- 27031799
TI  - Pseudomonas putida biofilm dynamics following a single pulse of silver
      nanoparticles.
AB  - Pseudomonas putida mono-species biofilms were exposed to silver nanoparticles (Ag
      NPs) in artificial wastewater (AW) under hydrodynamic conditions. Specifically,
      48 h old biofilms received a single pulse of Ag NPs at 0, 0.01, 0.1, 1, 10 and
      100 mg L(-1) for 24 h in confocal laser scanning microscopy (CLSM) compatible
      flow-cells. The biofilm dynamics (in terms of morphology, viability and activity)
      were characterised at 48, 72 and 96 h. Consistent patterns were found across flow
      cells and experiments at 48 h. Dose dependent impacts of NPs were then shown at
      72 h on biofilm morphology (e.g. biomass, surface area and roughness) from 0.01
      mg L(-1). The microbial viability was not altered below 10 mg L(-1) Ag NPs. The
      activity (based on the d-glucose utilisation) was impacted by concentrations of
      Ag NPs equal and superior to 10 mg L(-1). Partial recovery of morphology,
      viability and activity were finally observed at 96 h. Comparatively, exposure to
      Ag salt resulted in ca. one order of magnitude higher toxicity when compared to
      Ag NPs. Consequently, the use of a continuous culture system and incorporation of
      a recovery stage extends the value of biofilm assays beyond the standard acute
      toxicity assessment.

PMID- 27031801
TI  - Microbial bioavailability of 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) in
      natural sediments from major rivers of China.
AB  - Microbial degradation plays a crucial role in eliminating polybrominated diphenyl
      ethers (PBDEs) in environments. However, the microbial bioavailability of PBDEs
      in aquatic sediments is not well understood. In this work, the bioavailability of
      2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a typical PBDE congener, to PBDE
      degrading microorganisms in natural sediments from six Chinese rivers under
      anaerobic conditions was investigated. The contents of black carbon (BC) and
      total organic carbon (TOC) in the six sediment samples were in the range of
      0.025%-0.30% and 0.03%-3.38%, respectively. BDE-47 desorption from various
      sediments was fitted well with the first-order three-compartment desorption
      model. The desorbing fraction of sediment-associated BDE-47 at each desorption
      time interval exhibited a significant negative correlation with the BC content (p
      < 0.01). In the sediments, the anaerobic debromination of BDE-47 by
      microorganisms underwent a stepwise debromination pathway generating mainly three
      lower brominated congeners (BDE-28, -17 and -4). The microbial debromination
      ratio of BDE-47 ranged from 4.21% to 7.89% in various sediments after 120 d
      incubation anaerobically, and it negatively correlated with the content of
      sediment BC significantly (p < 0.01). However, the desorbing fraction and
      microbial debromination ratio of BDE-47 only showed weak correlations with the
      TOC content in sediments (p > 0.05). Furthermore, there was a significant
      positive correlation of desorbing fraction of BDE-47 from sediments with its
      microbial debromination ratio (p < 0.01) as well as with the level of its three
      lower brominated products (p < 0.05) after the first 20 d incubation. This study
      suggests that the BDE-47 bioavailability to microorganisms in anaerobic river
      sediments is mainly influenced by the content of sediment BC which controls the
      desorbing fraction of sediment-associated BDE-47.

PMID- 27031800
TI  - Adsorptive removal of antibiotics from aqueous solution using carbon materials.
AB  - Antibiotics, an important type of environmental contamination, have attracted
      many researchers to the study of their removal from aqueous solutions. Adsorption
      technology is a fast, efficient, and economical physicochemical method that is
      extensively used in wastewater treatment. From original activated carbon and
      carbon nanotubes to the latest graphene-based materials, carbon-based materials
      have been widely used as highly effective adsorbents for contaminant removal from
      aqueous solution because of their large specific surface area, high porosity, and
      high reaction activity. In this article, adsorption removal methods for four
      major types of antibiotic (tetracyclines, sulfonamides, macrolides, and
      quinolones) are reviewed. We also provide an overview of the application
      development of carbon materials as adsorbents for antibiotic removal from aqueous
      solution. The most promising works are discussed, and the main challenges in
      preparing high-performance adsorbents and the development tendency of adsorbents
      are also analyzed. This work provides theoretical guidance for subsequent
      research in the design and modification of carbon materials for applications in
      the adsorption removal of antibiotics from aqueous solution.

PMID- 27031802
TI  - Study on the kinetics and transformation products of salicylic acid in water via
      ozonation.
AB  - As salicylic acid is one of widely used pharmaceuticals, its residue has been
      found in various environmental water systems e.g. wastewater, surface water,
      treated water and drinking water. It has been reported that salicylic acid can be
      efficiently removed by advanced oxidation processes, but there are few studies on
      its transformation products and ozonation mechanisms during ozonation process.
      The objective of this study is to characterize the transformation products,
      investigate the degradation mechanisms at different pH, and propose the ozonation
      pathways of salicylic acid. The results showed that the rate of degradation was
      about 10 times higher at acidic condition than that at alkaline condition in the
      first 1 min when 1 mg L(-1) of ozone solution was added into 1 mg L(-1) of
      salicylic acid solution. It was proposed that ozone direct oxidation mechanism
      dominates at acidic condition, while indirect OH radical mechanism dominates at
      alkaline condition. A two stages pseudo-first order reaction was proposed at
      different pH conditions. Various hydroxylation products, carbonyl compounds and
      carboxylic acids, such as 2,5-dihydroxylbenzoic acid, 2,3-dihydroxylbenzoic acid,
      catechol, formaldehyde, glyoxal, acetaldehyde, maleic acid, acetic acid and
      oxalic acid etc. were identified as ozonation transformation products. In
      addition, acrylic acid was identified, for the first time, as ozonation
      transformation products through high resolution liquid chromatography-time of
      flight mass spectrometer. The information demonstrated in this study will help us
      to better understand the possible effects of ozonation products on the water
      quality. The degradation pathways of salicylic acid by ozonation in water sample
      were proposed. As both O3 and OH radical were important in the reactions, the
      degradation pathways of salicylic acid by ozonation in water sample were proposed
      at acidic and basic conditions. To our knowledge, there was no integrated study
      reported on the ozonation of salicylic acid in water, in terms of transformation
      products, kinetic, mechanism, as well as degradation pathways.

PMID- 27031803
TI  - Solid/liquid extraction equilibria of phenolic compounds with trioctylphosphine
      oxide impregnated in polymeric membranes.
AB  - Trioctylphosphine oxide based extractant impregnated membranes (EIM) were used
      for extraction of phenol and its methyl, hydroxyl and chloride substituted
      derivatives. The distribution coefficients of the phenols varied from 2 to 234,
      in the order of 1-napthol > p-chlorophenol > m-cresol > p-cresol > o-cresol >
      phenol > catechol > pyrogallol > hydroquinone, when initial phenols loadings was
      varied in 100-2000 mg/L. An extraction model, based on the law of mass action,
      was formulated to predict the equilibrium distribution of the phenols. The model
      was in excellent agreement (R(2) > 0.97) with the experimental results at low
      phenols concentrations (<800 mg/L). At higher phenols loadings though, Langmuir
      isotherm was better suited for equilibrium prediction (R(2) > 0.95), which
      signified high mass transfer resistance in the EIMs. Examination of the effects
      of ring substitution on equilibrium, and bivariate statistical analysis between
      the amounts of phenols extracted into the EIMs and factors affecting phenols
      interaction with TOPO, indicated the dominant role of hydrophobicity in
      equilibrium determination. These results improve understanding of the
      solid/liquid equilibrium process between phenols and the EIMs, and these will be
      useful in designing phenol recovery process from wastewater.

PMID- 27031804
TI  - Microcalorimetric studies on the energy release of isolated rat mitochondria
      under different concentrations of gadolinium (III).
AB  - Gadolinium-based compounds are most widely utilized for paramagnetic contrast
      agents, but, the toxicological mechanism of gadolinium (Gd) had not been fully
      elucidated since the first report about Gd anomaly. In this work, we analyzed the
      effect of Gd(3+) on mitochondria in vitro by microcalorimetry. Microcalorimetry
      can provide detailed kinetic and thermodynamic information from thermogenic
      curve. At the tested concentration, Gd(3+) induced the increase of growth rate
      constant (k1). At high concentration (100-500 MUM), the maximum power output time
      (tm), the decline rate constant (-k2) and the time of activity recovery phase
      (tR) decreased with the addition of Gd(3+) and the maximum power output (Pm)
      increased. At low concentration (0-100 MUM), the changes were different from high
      concentration. From the results we concluded that the effect of different
      concentrations of Gd(3+) had a relationship with time, high concentration of
      Gd(3+) induced mitochondrial energy metabolism disturb however low concentration
      may promote mitochondrial adaption to physiological stresses. The effect of low
      concentration of Gd(3+) need more work to elucidate the mechanism. The results of
      total heat output (Q) and mitochondrial respiratory activities suggested high
      concentrations of Gd(3+) could accelerate adenosine triphosphate (ATP)
      consumption under respiratory system damaged.

PMID- 27031805
TI  - Chronic fluoride exposure-induced testicular toxicity is associated with
      inflammatory response in mice.
AB  - Previous studies have indicated that fluoride (F) can affect testicular toxicity
      in humans and rodents. However, the mechanism underlying F-induced testicular
      toxicity is not well understood. This study was conducted to evaluate the sperm
      quality, testicular histomorphology and inflammatory response in mice followed F
      exposure. Healthy male mice were randomly divided into four groups with sodium
      fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the
      end of the exposure, significantly increased percentage of spermatozoa
      abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized
      spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of
      sperm cells were also observed in the NaF treated group. In addition, chronic F
      exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C
      (IL-17RC), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in
      transcriptional levels, as well as IL-17 and TNF-alpha levels in translational
      levels. Interestingly, we observed that F treated group elevated testicular
      inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO)
      concentration. Taken together, these results indicated that testicular
      inflammatory response could contribute to chronic F exposure induced testicular
      toxicity in mice.

PMID- 27031806
TI  - Decline in sediment contamination by persistent toxic substances from the outfall
      of wastewater treatment plant: Effectiveness of legislative actions in Korea.
AB  - Legacy and new persistent organic pollutants (POPs) and polycyclic aromatic
      hydrocarbons (PAHs) were measured in sediments near a wastewater treatment plant
      (WWTP) outfall in a semi-enclosed bay, to investigate the current contamination
      and temporal changes in these contaminants associated with regulation activities
      in Korea. The concentrations of most of the POPs showed clear decreasing trends
      with an increase in the distance from the WWTP outfall, indicating that the WWTP
      discharges greatly contributed to the sediment contamination by POPs. Highly
      significant correlations were found for most of the POPs, indicating a common
      source for sediment contamination. Significant declines were found in the
      concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs),
      dioxin-like polychlorinated biphenyls (DL-PCBs), polybrominated diphenyl ethers
      (PBDEs), and PAHs in the sediments collected between 2005 and 2013. This result
      suggested that legislative actions (regulation of the PCDD/Fs in flue gas, total
      pollution load management, and whole effluent toxicity for WWTP discharges) and
      change of fuels, were likely to be effective at reducing the POP and PAH levels
      in sediments during the past several years. The different compositional profiles
      of the PCDD/Fs and PAHs between 2005 and 2013 implied changes in and/or
      additional sources of these contaminants. Despite a decline in the PCDD/Fs over
      time, the present levels of PCDD/Fs in the sediment exceeded some of the sediment
      quality guidelines suggested by the National Oceanic and Atmospheric
      Administration.

PMID- 27031807
TI  - Cross flow ultrafiltration of Cr (VI) using MCM-41, MCM-48 and Faujasite (FAU)
      zeolite-ceramic composite membranes.
AB  - This work describes the removal of Cr (VI) from aqueous solution in cross flow
      mode using MCM-41, MCM-48 and FAU zeolite membranes prepared on circular shaped
      porous ceramic support. Ceramic support was manufactured using locally available
      clay materials via a facile uni-axial compaction method followed by sintering
      process. A hydrothermal technique was employed for the deposition of zeolites on
      the ceramic support. The porosity of ceramic support (47%) is reduced by the
      formation of MCM-41 (23%), MCM-48 (22%) and FAU (33%) zeolite layers. The pore
      size of the MCM-41, MCM-48 and FAU membrane is found to be 0.173, 0.142, and
      0.153 MUm, respectively, which is lower than that of the support (1.0 MUm). Cross
      flow ultrafiltration experiments of Cr (VI) were conducted at five different
      applied pressures (69-345 kPa) and three cross flow rates (1.11 * 10(-7) - 2.22 *
      10(-7) m(3)/s). The filtration studies inferred that the performance of the
      fabricated zeolite composite membranes is optimum at the maximum applied pressure
      (345 kPa) and the highest rejection is obtained with the lowest cross flow rate
      (1.11 * 10(-7) m(3)/s) for all three zeolite membrane. The permeate flux of MCM
      41, MCM-48 and FAU zeolite composite membranes are almost remained constant in
      the entire duration of the separation process. The highest removal of 82% is
      shown by FAU membrane, while MCM-41 and MCM-48 display 75% and 77% of Cr (VI)
      removal, respectively for the initial feed concentration of 1000 ppm with natural
      pH of the solution at an applied pressure of 345 kPa.

PMID- 27031808
TI  - Snowpack deposition of trace elements in the Athabasca oil sands region, Canada.
AB  - The total recoverable and dissolved concentrations of 29 metals and metalloids
      were analyzed in snowpack collected at 91 sites in the Athabasca oil sands
      region, Canada in winter 2011. Based on deposition pattern from geographical
      centre, three groups were found: Type-1 metals (i.e. dissolved and total
      recoverable V; Mo) showed a significant exponential decrease with distance,
      suggesting oil sands development sources; Type-2 elements (e.g. Al, Sb, As, Ba,
      Fe, Ni, Tl, and Ti and Zn) showed exponentially decline patterns but with some
      local point sources; Type-3 elements (e.g. Cd, Cl, Cr, Mn, Sr and Th) deposition
      pattern represented local sources. A self-organizing map showed that sites with
      the highest elemental concentrations (Cluster I) were mainly located in the
      vicinity of upgrading facilities and along the north-south transects. The lowest
      elemental concentration sites (Cluster III) were the most distal sites or located
      in the western region of the study area.

PMID- 27031809
TI  - The Utilization of Amide Groups To Expand and Functionalize Metal-Organic
      Frameworks Simultaneously.
AB  - A new stepwise ligand-elongation strategy by amide spacers is utilized to prepare
      isoreticularly high-porous metal-organic frameworks (MOFs), namely, quasi
      mesoporous [Cu2 (PDBAD)(H2 O)]n (H4 PDBAD=5,5'-((4,4'-((pyridine-3,5
      dicarbonyl)bis(azanediyl))bis(benzoyl))bis(azanediyl))diisophthalic acid; NJU
      Bai22: NJU-Bai for Nanjing University Bai's group), and mesoporous [Cu2
      (PABAD)(H2 O)]n (H4 PABAD=5,5'-((4,4'-((4,4'-((pyridine-3,5
      dicarbonyl)bis(azanediyl))bis(benzoyl))bis
      (azanediyl))bis(benzoyl))bis(azanediyl))diisophthalic acid; NJU-Bai23). Compared
      with the prototypical MOF of [Cu2 (PDAD)(H2 O)]n (H4 PDAD=5,5'-(pyridine-3,5
      dicarbonyl)bis(azanediyl)diisophthalic acid; NJU-Bai21, also termed as PCN-124),
      both MOFs exhibit almost the same CO2 adsorption enthalpy and CO2 selectivity
      values, and better capacity for CO2 storage under high pressure; these results
      make them promising candidate materials for CO2 capture and sequestration.
      Interestingly, this new method, in comparison with traditional strategies of
      using phenyl or triple-bond spacers, is easier and cheaper, resulting in a better
      ability to retain high CO2 affinity and selectivity in MOFs with large pores and
      high CO2 storage capacity. Additionally, it may lead to the high thermal
      stability of the MOFs and also their tolerance to water, which is related to the
      balance between the density of functional groups and pore sizes. Therefore, this
      strategy could provide new opportunities to explore more functionalized
      mesoporous MOFs with high performance. 

PMID- 27031810
TI  - MiRNA-124 induces neuroprotection and functional improvement after focal cerebral
      ischemia.
AB  - microRNA-124 (miR-124), the most abundant miRNA of the CNS, was recently shown to
      modulate the polarization of activated microglia and infiltrating macrophages
      towards the anti-inflammatory M2 phenotype and protect neurons in various ways
      after brain disease. In ischemic stroke, microglia and macrophages of a
      detrimental and persistent pro-inflammatory M1 phenotype have been shown to
      aggravate the secondary injury. Thus, shifting the polarization of
      microglia/macrophages into the beneficial, anti-inflammatory M2-like phenotype is
      considered neuroprotective after stroke onset. Here, we have induced 30 min
      transient occlusion of the right middle cerebral artery (MCAO) in 34 male,
      C57BL/6 mice. Lesion development was monitored with T2-weighted MRI. Liposomated
      miR-124 was injected in 11 animals at 48 h and in 5 animals at 10 days after
      MCAO. Arg-1, a marker for M2 phenotype, was co-stained with Iba-1, NeuN or GFAP.
      The distribution of astrocytes, neurons and microglia/macrophages and their
      expression of Arg-1 were quantified. Early miR-124 injection resulted in a
      significantly increased neuronal survival and a significantly increased number of
      M2-like polarized microglia/macrophages. Moreover, the lesion core, delineated by
      reactive astrocytes, was significantly reduced over time upon early miR-124
      injection. These neuroprotective and anti-inflammatory effects of the early miR
      124 treatment were pronounced during the first week with Arg-1. Number of Arg-1+
      microglia/macrophages correlated with neuronal protection and with functional
      improvement during the first week. Thus, our present results demonstrate that miR
      124 may serve as a novel therapeutic strategy for neuroprotection and functional
      recovery upon stroke onset.

PMID- 27031811
TI  - ECM hydrogel for the treatment of stroke: Characterization of the host cell
      infiltrate.
AB  - Brain tissue loss following stroke is irreversible with current treatment
      modalities. The use of an acellular extracellular matrix (ECM), formulated to
      produce a hydrogel in situ within the cavity formed by a stroke, was investigated
      as a method to replace necrotic debris and promote the infiltration of host brain
      cells. Based on magnetic resonance imaging measurements of lesion location and
      volume, different concentrations of ECM (0, 1, 2, 3, 4, 8 mg/mL) were injected at
      a volume equal to that of the cavity (14 days post-stroke). Retention of ECM
      within the cavity occurred at concentrations >3 mg/mL. A significant cell
      infiltration into the ECM material in the lesion cavity occurred with an average
      of ~36,000 cells in the 8 mg/mL concentration within 24 h. An infiltration of
      cells with distances of >1500 MUm into the ECM hydrogel was observed, but the
      majority of cells were at the tissue/hydrogel boundary. Cells were typically of a
      microglia, macrophage, or neural and oligodendrocyte progenitor phenotype. At the
      8 mg/mL concentration, ~60% of infiltrating cells were brain-derived phenotypes
      and 30% being infiltrating peripheral macrophages, polarizing toward an M2-like
      anti-inflammatory phenotype. These results suggest that an 8 mg/mL ECM
      concentration promotes a significant acute endogenous repair response that could
      potentially be exploited to treat stroke.

PMID- 27031812
TI  - Melanin nanoparticles derived from a homology of medicine and food for sentinel
      lymph node mapping and photothermal in vivo cancer therapy.
AB  - The use of non-toxic or low toxicity materials exhibiting dual functionality for
      use in sentinel lymph node (SLN) mapping and cancer therapy has attracted
      considerable attention during the past two decades. Herein, we report that the
      natural black sesame melanin (BSM) extracted from black sesame seeds (Sesamum
      indicum L.) shows exciting potential for SLN mapping and cancer photothermal
      therapy. Aqueous solutions of BSM under neutral and alkaline conditions can
      assemble into sheet-like nanoparticles ranging from 20 to 200 nm in size. The BSM
      nanoparticles were encapsulated by liposomes to improve their water solubility
      and the encapsulated and bare BSM nanoparticles were both non-toxic to cells.
      Furthermore, the liposome-encapsulated BSM nanoparticles (liposome-BSM) did not
      exhibit any long-term toxicity in mice. The liposome-BSM nanoparticles were
      subsequently used to passively target healthy and tumor-bearing mice SLNs, which
      were identified by the black color of the nanoparticles. BSM also strongly
      absorbed light in the near-infrared (NIR) range, which was rapidly converted to
      heat energy. Human esophagus carcinoma cells (Eca-109) were killed efficiently by
      liposome-BSM nanocomposites upon NIR laser irradiation. Furthermore, mouse tumor
      tissues grown from Eca-109 cells were seriously damaged by the photothermal
      effects of the liposome-BSM nanocomposites, with significant tumor growth
      suppression compared with controls. Given that BSM is a safe and nutritious
      biomaterial that can be easily obtained from black sesame seed, the results
      presented herein represent an important development in the use of natural
      biomaterials for clinical SLN mapping and cancer therapy.

PMID- 27031813
TI  - Ocular Toxoplasmosis Reactivation in a Patient With Inflammatory Bowel Disease
      Under Treatment With Azathioprine.

PMID- 27031814
TI  - Primary Health Care Research & Development: Official Journal of the European
      Forum for Primary Care.

PMID- 27031815
TI  - Group exercise and self-management for older adults with osteoarthritis: a
      feasibility study.
AB  - BACKGROUND: Osteoarthritis (OA) is a common condition expected to be the fourth
      leading cause of disability by the year 2020. Treatment with non-steroidal anti
      inflammatory drugs is problematic in older adults (>75 years) where the presence
      of comorbidities is more prevalent. Exercise has been recommended irrespective of
      age and comorbidity. The purpose of this project was to develop a combined
      exercise and self-management intervention to help older adults with OA to manage
      their comorbidities. METHODS: Literature reviews were conducted to inform the
      development of an intervention followed by a pilot study to assess feasibility
      and test outcome measures. Participant interviews and session observation were
      used to evaluate the pilot study. RESULTS: Evidence from the literature reviews
      suggested that a combined intervention consisting of behavioural change/self
      management education and exercise was the most appropriate. Each component was
      developed and then tested as a combined package in a pilot study which comprised
      12 sessions delivered over six weeks. Four males and six females aged between 75
      and 92 years took part. The average attendance was 89%. Most participants
      reported some benefit and satisfaction with the programme along with changes in
      physical ability. The majority of participants continued with some form of
      exercise at three months. CONCLUSION: The intervention was well received and has
      encouraged 80% of participants to continue exercising after the programme. The
      small but positive changes seen in comorbidities, benefit of the intervention,
      satisfaction and general health are promising. Randomised controlled trial
      evidence of effectiveness and cost effectiveness is needed before such
      interventions can be recommended.

PMID- 27031816
TI  - MCI circular on research publications: Missing the wood for the trees?
AB  - We read with interest the editorial "Regressive trend: MCI's approach to
      assessment of medical teachers' performance". MCI is the holy cow of medical
      education, and we are yet to see a detailed critique of its various policies.
      India lags behind in evidence-based health policies as well as those that
      regulate education. It was not surprising to see the regulations on research
      publication in the context of promotion. It was shocking that the circular has
      numerous typos, which erode one's credibility. Historically, typos have resulted
      in regime changes and company liquidations.

PMID- 27031817
TI  - Estimating Contraceptive Needs and Increasing Access to Contraception in Response
      to the Zika Virus Disease Outbreak--Puerto Rico, 2016.
AB  - Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes.
      Increasing evidence links Zika virus infection during pregnancy to adverse
      pregnancy and birth outcomes, including pregnancy loss, intrauterine growth
      restriction, eye defects, congenital brain abnormalities, and other fetal
      abnormalities. The virus has also been determined to be sexually transmitted.
      Because of the potential risks associated with Zika virus infection during
      pregnancy, CDC has recommended that health care providers discuss prevention of
      unintended pregnancy with women and couples who reside in areas of active Zika
      virus transmission and do not want to become pregnant. However, limitations in
      access to contraception in some of these areas might affect the ability to
      prevent an unintended pregnancy. As of March 16, 2016, the highest number of Zika
      virus disease cases in the United States and U.S. territories were reported from
      Puerto Rico. The number of cases will likely rise with increasing mosquito
      activity in affected areas, resulting in increased risk for transmission to
      pregnant women. High rates of unintended and adolescent pregnancies in Puerto
      Rico suggest that, in the context of this outbreak, access to contraception might
      need to be improved. CDC estimates that 138,000 women of reproductive age (aged
      15-44 years) in Puerto Rico do not desire pregnancy and are not using one of the
      most effective or moderately effective contraceptive methods, and therefore might
      experience an unintended pregnancy. CDC and other federal and local partners are
      seeking to expand access to contraception for these persons. Such efforts have
      the potential to increase contraceptive access and use, reduce unintended
      pregnancies, and lead to fewer adverse pregnancy and birth outcomes associated
      with Zika virus infection during pregnancy. The assessment of challenges and
      resources related to contraceptive access in Puerto Rico might be a useful model
      for other areas with active transmission of Zika virus.

PMID- 27031818
TI  - Psychological and educational interventions for subfertile men and women.
AB  - BACKGROUND: Approximately one-fifth of all subfertile couples seeking fertility
      treatment show clinically relevant levels of anxiety, depression, or distress.
      Psychological and educational interventions are frequently offered to subfertile
      couples, but their effectiveness, both in improving mental health and pregnancy
      rates, is unclear. OBJECTIVES: To assess the effectiveness of psychological and
      educational interventions for subfertile couples on psychological and fertility
      treatment outcomes. SEARCH METHODS: We searched (from inception to 2 April 2015)
      the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled
      Trials, the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2,
      2015), MEDLINE, EMBASE, PsycINFO, EBSCO CINAHL, DARE, Web of Science, OpenGrey,
      LILACS, PubMed, and ongoing trials registers. We handsearched reference lists and
      contacted experts in the field. SELECTION CRITERIA: We included published and
      unpublished randomised controlled trials (RCTs), cluster randomised trials, and
      cross-over trials (first phase) evaluating the effectiveness of psychological and
      educational interventions on psychological and fertility treatment outcomes in
      subfertile couples. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial risk of bias and extracted data. We contacted study
      authors for additional information. Our primary outcomes were psychological
      measures (anxiety and depression) and fertility rates (live birth or ongoing
      pregnancy). We assessed the overall quality of the evidence using GRADE
      criteria.As we did not consider the included studies to be sufficiently similar
      to permit meaningful pooling, we summarised the results of the individual studies
      by presenting the median and interquartile range (IQR) of effects as well as the
      minimum and maximum values. We calculated standardised mean differences (SMDs)
      for continuous variables and odds ratios (ORs) for dichotomous outcomes. MAIN
      RESULTS: We included 39 studies involving 4925 participants undergoing assisted
      reproductive technology. Studies were heterogeneous with respect to a number of
      factors, including nature and duration of interventions, participants, and
      comparator groups. As a result, we judged that pooling results would not result
      in a clinically meaningful estimate of a treatment effect. There were substantial
      methodological weaknesses in the studies, all of which were judged to be at high
      risk of bias for one or more quality assessment domains. There was concern about
      attrition bias (24 studies), performance bias for psychological outcomes (27
      studies) and fertility outcomes (18 studies), and detection bias for
      psychological outcomes (26 studies). We therefore considered study-specific
      estimates of intervention effects to be unreliable. Thirty-three studies reported
      the outcome mental health. Only two studies reported the outcome live birth, and
      both of these had substantial attrition. One study reported ongoing pregnancy,
      again with substantial attrition. We have combined live birth and ongoing
      pregnancy in one outcome. Psychological outcomesStudies utilised a variety of
      measures of anxiety and depression. In all cases a low score denoted benefit from
      the intervention.SMDs for anxiety were as follows: psychological interventions
      versus attentional control or usual care: median (IQR) = -0.30 (-0.84 to 0.00),
      minimum value -5.13; maximum value 0.84, 17 RCTs, 2042 participants; educational
      interventions versus attentional control or usual care: median = 0.03, minimum
      value -0.38; maximum value 0.23, 4 RCTs, 330 participants.SMDs for depression
      were as follows: psychological interventions versus attentional control or usual
      care: median (IQR) = -0.45 (-0.68 to -0.08), minimum value -3.01; maximum value
      1.23, 12 RCTs, 1160 participants; educational interventions versus attentional
      control or usual care: median = -0.33, minimum value -0.46; maximum value 0.17, 3
      RCTs, 304 participants. Fertility outcomesWhen psychological interventions were
      compared with attentional control or usual care, ORs for live birth or ongoing
      pregnancy ranged from minimum value 1.13 to maximum value 10.05. No studies of
      educational interventions reported this outcome. AUTHORS' CONCLUSIONS: The
      effects of psychological and educational interventions on mental health including
      distress, and live birth or ongoing pregnancy rates is uncertain due to the very
      low quality of the evidence. Existing trials of psychological and educational
      interventions for subfertility were generally poorly designed and executed,
      resulting in very serious risk of bias and serious inconsistency in study
      findings. There is a need for studies employing appropriate methodological
      techniques to investigate the benefits of these treatments for this population.
      In particular, attentional control groups should be employed, that is groups
      receiving a treatment that mimics the amount of time and attention received by
      the treatment group but is not thought to have a specific effect upon the
      participants, in order to distinguish between therapeutic and non-specific
      effects of interventions. Where attrition cannot be minimised, appropriate
      statistical techniques for handling drop-out must be applied. Failure to address
      these issues in study design has resulted in studies that do not provide a valid
      basis for answering questions about the effectiveness of these interventions.

PMID- 27031819
TI  - Long mitral valve leaflets determine left ventricular outflow tract obstruction
      during exercise in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Development of left ventricular outflow tract obstruction (LVOTO) in
      patients with hypertrophic cardiomyopathy (HCM) is important for explaining
      symptoms and designing management. LVOTO is mostly caused by a combination of
      septal hypertrophy and systolic anterior movement of the mitral valve (SAM). The
      aim of the present study was to determine predictors of exercise induced LVOTO in
      a group of HCM patients. METHODS: We performed supine exercise Doppler
      echocardiography, including measurements of LV morphology and function and
      anterior mitral leaflet length, in 51 mildly symptomatic HCM (septal
      thickness>=15mm) and compared them with 50 healthy controls. Measurements were
      made at 1) rest, 2) Valsalva maneuver, 3) peak exercise and 4) post exercise.
      LVOTO was diagnosed as a LVOT gradient of >30mmHg at rest, after Valsalva and
      after exercise or >=50mmHg at peak exercise. RESULTS: All patients stopped
      exercise because of exhaustion. 35% of the patients had resting LVOTO and 48%
      during Valsalva. At peak exercise, only 37% had LVOTO, who increased to 64% post
      exercise. Patients who developed LVOTO at peak exercise were more prone to
      continue having it post exercise (p<0.001), to have attenuated systolic blood
      pressure rise (p=0.011) and to have long anterior mitral valve leaflets
      (p<0.001). Backward multiple regression analysis showed the anterior mitral
      leaflet length as the strongest single independent predictor (beta=0.36, p=0.010)
      for increased LVOT velocities, followed by basal septal thickness. CONCLUSION: In
      patients with HCM, LV outflow tract obstruction seems to be relatively uncommon
      during exercise but rather occurring minutes after stopping exercise. Exercise
      LVOTO seems to be determined by long anterior mitral leaflets in addition to the
      well established septal hypertrophy.

PMID- 27031820
TI  - Carabin: Endogenous calcineurin inhibitor, a potential diagnostic and therapeutic
      target for cardiac hypertrophy in heart failure.

PMID- 27031821
TI  - The nature of P-wave dispersion - A clinically useful parameter that does not
      exist.

PMID- 27031822
TI  - Physical activity with alanine aminotransferase and gamma-glutamyltransferase
      among congestive heart failure patients.

PMID- 27031823
TI  - Clinical and angiographic characteristics of patients undergoing cardiac
      catheterization shortly after coronary bypass grafting: A single center
      experience.

PMID- 27031824
TI  - Cataract surgery is more prevalent and occurs at an earlier age in a high
      cardiovascular risk cohort: Comparison with the Blue Mountains Eye Study.

PMID- 27031825
TI  - Non-metric variation of the middle phalanges of the human toes (II-V): long/short
      types and their evolutionary significance.
AB  - The human lateral toes are characterised by extreme reduction compared with other
      primates, and in particular other hominoids. Some phalangeal non-metric variants
      have been well identified in humans, in particular: triphalangeal/biphalangeal
      patterns, and the presence/absence of phalangeal secondary centres of
      ossification. The purpose of the present study was to describe and analyse an
      original non-metric variation of the middle phalanges of the lateral toes. The
      material consisted of 2541 foot radiographs that came from 2541 different
      European adult individuals. Two morphological types of the middle phalanx were
      defined as a simple binary trait: long type (L) and short type (S). In feet with
      a triphalangeal pattern in all lateral toes (1413 cases), a mediolateral
      increasing gradient was observed in the occurrence of type S: 8.1% in II; 30.7%
      in III; 68.4% in IV; and 99.1% in V. In feet with a biphalangeal pattern in one
      or more lateral toes (III-V; 1128 cases), type S occurred more frequently than in
      triphalangeal feet. Of the 30 theoretical arrangements of the L/S types in the
      lateral toes (II-V) in a complete foot, only 13 patterns were observed. Seven
      patterns represented 95.6% of the population: LLSS (20.9%), LLLS (17.1%), LSS
      (15.9%), SSS (14.5%), LSSS (12.7%), LLS (10.1%) and SSSS (4.4%). Type L can be
      interpreted as the primitive pattern (plesiomorphy), and type S as a derived
      pattern (apomorphy) that seems specific to the human species (i.e. autapomorphy).
      Within the specific evolution of the human foot in relation to the acquisition of
      constant erect posture and bipedalism, the short type of the middle phalanges can
      reasonably be considered as directly linked to the reduction of the lateral toes.

PMID- 27031826
TI  - Pathological evidence of foreign body reaction induced by bee sting therapy.

PMID- 27031827
TI  - The Effects of Anthropogenic Structures on Habitat Connectivity and the Potential
      Spread of Non-Native Invertebrate Species in the Offshore Environment.
AB  - Offshore structures provide habitat that could facilitate species range
      expansions and the introduction of non-native species into new geographic areas.
      Surveys of assemblages of seven offshore oil and gas platforms in the Santa
      Barbara Channel revealed a change in distribution of the non-native sessile
      invertebrate Watersipora subtorquata, a bryozoan with a planktonic larval
      duration (PLD) of 24 hours or less, from one platform in 2001 to four platforms
      in 2013. We use a three-dimensional biophysical model to assess whether larval
      dispersal via currents from harbors to platforms and among platforms is a
      plausible mechanism to explain the change in distribution of Watersipora and to
      predict potential spread to other platforms in the future. Hull fouling is
      another possible mechanism to explain the change in distribution of Watersipora.
      We find that larval dispersal via currents could account for the increase in
      distribution of Watersipora from one to four platforms and that Watersipora is
      unlikely to spread from these four platforms to additional platforms through
      larval dispersal. Our results also suggest that larvae with PLDs of 24 hours or
      less released from offshore platforms can attain much greater dispersal distances
      than larvae with PLDs of 24 hours or less released from nearshore habitat. We
      hypothesize that the enhanced dispersal distance of larvae released from offshore
      platforms is driven by a combination of the offshore hydrodynamic environment,
      larval behavior, and larval release above the seafloor. 

PMID- 27031828
TI  - Weight Loss Associated with Platinum-Based Chemotherapy in Patients with Advanced
      Lung Cancer.
AB  - BACKGROUND: We examined whether the weight loss that occurs with platinum-based
      chemotherapy in lung cancer patients is associated with chemotherapy side
      effects, treatment completion rates and therapeutic effect. METHODS: We
      retrospectively reviewed charts of advanced lung cancer patients treated with >=2
      cycles of platinum-based chemotherapy. Patients were divided into 2 groups based
      on >=5 or <5% weight loss. Relationships between weight loss and other variables
      were investigated. RESULTS: Among 114 patients, 18 (15.8%) experienced >=5%
      weight loss. Significantly more patients with small-cell lung cancer (SCLC) than
      with non-SCLC were found to have >=5% weight loss (30.8 vs. 11.4%, p = 0.023).
      Patients with >=5% weight loss experienced higher incidences of grade 3-4
      leukopenia (p = 0.008) and neutropenia (p = 0.005), and treatment completion
      rates were lower in this group (p = 0.035). Weight loss was not significantly
      associated with therapeutic effect. CONCLUSION: The weight loss in patients with
      advanced lung cancer receiving platinum-based chemotherapy is associated with
      SCLC, grade 3-4 leukopenia, neutropenia and a decrease in treatment completion
      rate.

PMID- 27031829
TI  - Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1
      and the Hepatitis C Virus.
AB  - Hepatitis C virus (HCV) is an oncogenic virus associated with the onset of
      hepatocellular carcinoma (HCC). The present study investigated the possible link
      between HCV infection and Netrin-1, a ligand for dependence receptors that
      sustains tumorigenesis, in particular in inflammation-associated tumors. We show
      that Netrin-1 expression is significantly elevated in HCV+ liver biopsies
      compared to hepatitis B virus (HBV+) and uninfected samples. Furthermore, Netrin
      1 was upregulated in all histological stages of HCV+ hepatic lesions, from
      minimal liver fibrosis to cirrhosis and HCC, compared to histologically matched
      HCV- tissues. Both cirrhosis and HCV contributed to the induction of Netrin-1
      expression, whereas anti-HCV treatment resulted in a reduction of Netrin-1
      expression. In vitro, HCV increased the level and translation of Netrin-1 in a
      NS5A-La-related protein 1 (LARP1)-dependent fashion. Knockdown and forced
      expression experiments identified the receptor uncoordinated receptor-5 (UNC5A)
      as an antagonist of the Netrin-1 signal, though it did not affect the death of
      HCV-infected cells. Netrin-1 enhanced infectivity of HCV particles and promoted
      viral entry by increasing the activation and decreasing the recycling of the
      epidermal growth factor receptor (EGFR), a protein that is dysregulated in HCC.
      Netrin-1 and HCV are, therefore, reciprocal inducers in vitro and in patients, as
      seen from the increase in viral morphogenesis and viral entry, both phenomena
      converging toward an increase in the level of infectivity of HCV virions. This
      functional association involving a cancer-related virus and Netrin-1 argues for
      evaluating the implication of UNC5 receptor ligands in other oncogenic microbial
      species. 

PMID- 27031830
TI  - Effect of the Fatigue Induced by a 110-km Ultramarathon on Tibial Impact
      Acceleration and Lower Leg Kinematics.
AB  - Ultramarathon runners are exposed to a high number of impact shocks and to severe
      neuromuscular fatigue. Runners may manage mechanical stress and muscle fatigue by
      changing their running kinematics. Our purposes were to study (i) the effects of
      a 110-km mountain ultramarathon (MUM) on tibial shock acceleration and lower limb
      kinematics, and (ii) whether kinematic changes are modulated according to the
      severity of neuromuscular fatigue. Twenty-three runners participated in the
      study. Pre- and post-MUM, neuromuscular tests were performed to assess knee
      extensor (KE) and plantar flexor (PF) central and peripheral fatigue, and a
      treadmill running bouts was completed during which step frequency, peak
      acceleration, median frequency and impact frequency content were measured from
      tibial acceleration, as well as foot-to-treadmill, tibia-to-treadmill, and ankle
      flexion angles at initial contact, and ankle range of motion using video
      analysis. Large neuromuscular fatigue, including peripheral changes and deficits
      in voluntary activation, was observed in KE and PF. MVC decrements of ~35% for KE
      and of ~28% for PF were noted. Among biomechanical variables, step frequency
      increased by ~2.7% and the ankle range of motion decreased by ~4.1% post-MUM.
      Runners adopting a non rearfoot strike pre-MUM adopted a less plantarflexed foot
      strike pattern post-MUM while those adopting a rearfoot strike pre-MUM tended to
      adopt a less dorsiflexed foot strike pattern post-MUM. Positive correlations were
      observed between percent changes in peripheral PF fatigue and the ankle range of
      motion. Peripheral PF fatigue was also significantly correlated to both percent
      changes in step frequency and the ankle angle at contact. This study suggests
      that in a fatigued state, ultratrail runners use compensatory/protective
      adjustments leading to a flatter foot landing and this is done in a fatigue dose
      dependent manner. This strategy may aim at minimizing the overall load applied to
      the musculoskeletal system, including impact shock and muscle stretch. 

PMID- 27031831
TI  - MeltMan: Optimization, Evaluation, and Universal Application of a qPCR System
      Integrating the TaqMan qPCR and Melting Analysis into a Single Assay.
AB  - In the present work, we optimised and evaluated a qPCR system integrating 6-FAM
      (6-carboxyfluorescein)-labelled TaqMan probes and melting analysis using the SYTO
      82 (S82) DNA binding dye in a single reaction. We investigated the influence of
      the S82 on various TaqMan and melting analysis parameters and defined its optimal
      concentration. In the next step, the method was evaluated in 36 different TaqMan
      assays with a total of 729 paired reactions using various DNA and RNA templates,
      including field specimens. In addition, the melting profiles of interest were
      correlated with the electrophoretic patterns. We proved that the S82 is fully
      compatible with the FAM-TaqMan system. Further, the advantages of this approach
      in routine diagnostic TaqMan qPCR were illustrated with practical examples. These
      included solving problems with flat or other atypical amplification curves or
      even false negativity as a result of probe binding failure. Our data clearly show
      that the integration of the TaqMan qPCR and melting analysis into a single assay
      provides an additional control option as well as the opportunity to perform more
      complex analyses, get more data from the reactions, and obtain analysis results
      with higher confidence. 

PMID- 27031832
TI  - Comparison of Deconvolution Filters for Photoacoustic Tomography.
AB  - In this work, we compare the merits of three temporal data deconvolution methods
      for use in the filtered backprojection algorithm for photoacoustic tomography
      (PAT). We evaluate the standard Fourier division technique, the Wiener
      deconvolution filter, and a Tikhonov L-2 norm regularized matrix inversion
      method. Our experiments were carried out on subjects of various appearances,
      namely a pencil lead, two man-made phantoms, an in vivo subcutaneous mouse tumor
      model, and a perfused and excised mouse brain. All subjects were scanned using an
      imaging system with a rotatable hemispherical bowl, into which 128 ultrasound
      transducer elements were embedded in a spiral pattern. We characterized the
      frequency response of each deconvolution method, compared the final image quality
      achieved by each deconvolution technique, and evaluated each method's robustness
      to noise. The frequency response was quantified by measuring the accuracy with
      which each filter recovered the ideal flat frequency spectrum of an
      experimentally measured impulse response. Image quality under the various
      scenarios was quantified by computing noise versus resolution curves for a point
      source phantom, as well as the full width at half maximum (FWHM) and contrast-to
      noise ratio (CNR) of selected image features such as dots and linear structures
      in additional imaging subjects. It was found that the Tikhonov filter yielded the
      most accurate balance of lower and higher frequency content (as measured by
      comparing the spectra of deconvolved impulse response signals to the ideal flat
      frequency spectrum), achieved a competitive image resolution and contrast-to
      noise ratio, and yielded the greatest robustness to noise. While the Wiener
      filter achieved a similar image resolution, it tended to underrepresent the lower
      frequency content of the deconvolved signals, and hence of the reconstructed
      images after backprojection. In addition, its robustness to noise was poorer than
      that of the Tikhonov filter. The performance of the Fourier filter was found to
      be the poorest of all three methods, based on the reconstructed images' lowest
      resolution (blurriest appearance), generally lowest contrast-to-noise ratio, and
      lowest robustness to noise. Overall, the Tikhonov filter was deemed to produce
      the most desirable image reconstructions. 

PMID- 27031834
TI  - A decision support tool to determine cost-to-benefit of a family-centered in-home
      program for at-risk adolescents.
AB  - Family-centered program research has demonstrated its effectiveness in improving
      adolescent outcomes. However, given current fiscal constraints faced by
      governmental agencies, a recent report from the Institute of Medicine and
      National Research Council highlighted the need for cost-benefit analyses to
      inform decision making by policymakers. Furthermore, performance management tools
      such as balanced scorecards and dashboards do not generally include cost-benefit
      analyses. In this paper, we describe the development of an Excel-based decision
      support tool that can be used to evaluate a selected family-based program for at
      risk children and adolescents relative to a comparison program or the status quo.
      This tool incorporates the use of an efficient, user-friendly interface with
      results provided in concise tabular and graphical formats that may be interpreted
      without need for substantial training in economic evaluation. To illustrate, we
      present an application of this tool to evaluate use of Boys Town's In-Home Family
      Services (IHFS) relative to detention and out-of-home placement in New York City.
      Use of the decision support tool can help mitigate the need for programs to
      contract experts in economic evaluation, especially when there are financial or
      time constraints.

PMID- 27031833
TI  - DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and
      Reduces Autoimmune Arthritis.
AB  - Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for
      various inflammatory conditions as well as for cancer. Despite its widespread
      use, there is a paucity of data regarding its safety and efficacy as well as its
      mechanism of action in human cells. Herein, we demonstrate that DMSO has ex-vivo
      anti-inflammatory activity using Escherichia coli- (E. coli) and herpes simplex
      virus-1 (HSV-1)-stimulated whole human blood. Specifically, we found that between
      0.5%-2%, DMSO significantly suppressed the expression of many pro-inflammatory
      cytokines/chemokines and prostaglandin E2 (PGE2). However, a significant
      reduction in monocyte viability was also observed at 2% DMSO, suggesting a narrow
      window of efficacy. Anti-inflammatory concentrations of DMSO suppressed E. coli
      induced ERK1/2, p38, JNK and Akt phosphorylation, suggesting DMSO acts on these
      signaling pathways to suppress inflammatory cytokine/chemokine production.
      Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro,
      topical administration of DMSO to mice subcutaneously implanted with B16 melanoma
      cells was ineffective at reducing tumor growth, DMSO was also found to block
      mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may
      contribute to its inability to slow tumor growth. Topical administration of DMSO,
      however, significantly mitigated K/BxN serum-induced arthritis in mice, and this
      was associated with reduced levels of pro-inflammatory cytokines in the joints
      and white blood cell levels in the blood. Thus, while we cannot confirm the
      efficacy of DMSO as an anti-cancer agent, the use of DMSO in arthritis warrants
      further investigation to ascertain its therapeutic potential.

PMID- 27031835
TI  - siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus
      Infection.
AB  - Little is known about the repertoire of cellular factors involved in the
      replication of pathogenic alphaviruses. To uncover molecular regulators of
      alphavirus infection, and to identify candidate drug targets, we performed a high
      content imaging-based siRNA screen. We revealed an actin-remodeling pathway
      involving Rac1, PIP5K1- alpha, and Arp3, as essential for infection by pathogenic
      alphaviruses. Infection causes cellular actin rearrangements into large bundles
      of actin filaments termed actin foci. Actin foci are generated late in infection
      concomitantly with alphavirus envelope (E2) expression and are dependent on the
      activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected
      cells and co-localizes with Rac1-PIP5K1-alpha along actin filaments in the
      context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors
      interfere with E2 trafficking from the trans-Golgi network to the cell surface,
      suggesting a plausible model in which transport of E2 to the cell surface is
      mediated via Rac1- and Arp3-dependent actin remodeling. 

PMID- 27031836
TI  - Dynamic Modelling of Tooth Deformation Using Occlusal Kinematics and Finite
      Element Analysis.
AB  - BACKGROUND: Dental biomechanics based on finite element (FE) analysis is
      attracting enormous interest in dentistry, biology, anthropology and
      palaeontology. Nonetheless, several shortcomings in FE modeling exist, mainly due
      to unrealistic loading conditions. In this contribution we used kinematics
      information recorded in a virtual environment derived from occlusal contact
      detection between high resolution models of an upper and lower human first molar
      pair (M1 and M1, respectively) to run a non-linear dynamic FE crash colliding
      test. METHODOLOGY: MicroCT image data of a modern human skull were segmented to
      reconstruct digital models of the antagonistic right M1 and M1 and the dental
      supporting structures. We used the Occlusal Fingerprint Analyser software to
      reconstruct the individual occlusal pathway trajectory during the power stroke of
      the chewing cycle, which was applied in a FE simulation to guide the M1 3D-path
      for the crash colliding test. RESULTS: FE analysis results showed that the stress
      pattern changes considerably during the power stroke, demonstrating that
      knowledge about chewing kinematics in conjunction with a morphologically detailed
      FE model is crucial for understanding tooth form and function under physiological
      conditions. CONCLUSIONS/SIGNIFICANCE: Results from such advanced dynamic
      approaches will be applicable to evaluate and avoid mechanical failure in
      prosthodontics/endodontic treatments, and to test material behavior for modern
      tooth restoration in dentistry. This approach will also allow us to improve our
      knowledge in chewing-related biomechanics for functional diagnosis and therapy,
      and it will help paleoanthropologists to illuminate dental adaptive processes and
      morphological modifications in human evolution.

PMID- 27031837
TI  - Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous
      Cell Carcinoma.
AB  - BACKGROUND: Cathepsin B (CTSB), a member of the cathepsin family, is a cysteine
      protease that is widely distributed in the lysosomes of cells in various tissues.
      It is overexpressed in several human cancers and may be related to tumorigenesis.
      The main purpose of this study was to analyze CTSB expression in oral squamous
      cell carcinoma (OSCC) and its correlation with patient prognosis.
      METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays were used to detect CTSB
      expression in 280 patients and to examine the association between CTSB expression
      and clinicopathological parameters. In addition, the metastatic effects of the
      CTSB knockdown on two oral cancer cell lines were investigated by transwell
      migration assay. Cytoplasmic CTSB expression was detected in 34.6% (97/280) of
      patients. CTSB expression was correlated with positive lymph node metastasis (p =
      0.007) and higher tumor grade (p = 0.008) but not with tumor size and distant
      metastasis. In addition, multivariate analysis using a Cox proportional hazards
      model revealed a higher hazard ratio, demonstrating that CTSB expression was an
      independent unfavorable prognostic factor in buccal mucosa carcinoma patients.
      Furthermore, the Kaplan-Meier curve revealed that buccal mucosa OSCC patients
      with positive CTSB expression had significantly shorter overall survival.
      Moreover, treatment with the CTSB siRNA exerted an inhibitory effect on migration
      in OC2 and CAL27 oral cancer cells. CONCLUSIONS: We conclude that CTSB expression
      may be useful for determining OSCC prognosis, particularly for patients with
      lymph node metastasis, and may function as a biomarker of the survival of OSCC
      patients in Taiwan.

PMID- 27031838
TI  - Total Retinal Blood Flow in a Nonhuman Primate Optic Nerve Transection Model
      Using Dual-Beam Bidirectional Doppler FD-OCT and Microsphere Method.
AB  - PURPOSE: We validated noninvasive Doppler-optical coherence tomography (OCT)
      blood flow measurements against the terminal microsphere method in a surgical
      induced optic nerve transection nonhuman primate model. METHODS: In 6 nonhuman
      primates, total retinal blood flow (TRBF) was measured with a custom-built dual
      beam bidirectional Doppler Fourier Domain (FD)-OCT. Peripapillary retinal nerve
      fiber layer thickness (RNFLT) was measured by Spectralis spectral-domain (SD)
      OCT. Measurements were performed every 10 to 15 days before and after unilateral
      optic nerve transection (ONT) until RNFLT was reduced by more than 40% from
      baseline. Before the animals were killed, TRBF was measured using the microsphere
      technique. RESULTS: A significant correlation between all arterial and venous
      Doppler OCT TRBF measurements was found in ONT and contralateral control eyes
      (both P < 0.01, n = 6). The Bland-Altman analysis showed a bias of 0.57 in the
      ONT group and 0.02 in the contralateral control group. Also, excellent agreement
      was observed between Doppler OCT and microsphere measurements (P < 0.01, r =
      0.976, bias = 0.54). After ONT, TRBF and RNFLT decreased by -51% +/- 42% and -44%
      +/- 2% (n = 5), respectively. In the contralateral control eyes, TRBF and RNFLT
      were unchanged. CONCLUSIONS: Very good accordance was found between TRBF
      measurements, obtained with dual-beam bidirectional Doppler FD-OCT and the
      microsphere method. It also was possible to monitor changes over time in TRBF
      after ONT with Doppler OCT. These findings highlight the accuracy and potential
      of noninvasive Doppler OCT to provide valuable information for detecting early
      changes in ocular disease in future.

PMID- 27031839
TI  - Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the
      CCR7-CCL19/21 Axis.
AB  - PURPOSE: The graft site microenvironment has a profound effect on alloimmunity
      and graft survival. We aimed to study the kinetics and phenotype of trafficking
      antigen-presenting cells (APC) to the draining lymph nodes (DLNs) in a mouse
      model of corneal transplantation, and to evaluate the homing mechanisms through
      which graft site inflammation controls APC trafficking. METHODS: Allogeneic donor
      corneas were transplanted onto inflamed or quiescent graft beds. Host- (YAe+) and
      donor (CD45.1+ or eGFP+)-derived APCs were analyzed by flow cytometry. Protein
      and mRNA expression of the CC chemokine receptor (CCR)7 ligands CCL19 and CCL21
      were assessed using ELISA and Real-Time qPCR, respectively. Transwell migration
      assay was performed to assess the effect of DLNs isolated from hosts with
      inflamed graft beds on mature bone marrow-derived dendritic cells (BMDCs).
      RESULTS: We found that inflamed graft sites greatly promote the trafficking of
      both recipient- and graft-derived APCs, in particular mature CCR7+ CD11c+
      dendritic cells (DC). CCL19 and CCL21 were expressed at significantly higher
      levels in the DLNs of recipients with inflamed graft beds. The supernatant of
      DLNs from recipients with inflamed graft beds induced a marked increase in mature
      DC migration compared with supernatant from recipients with quiescent graft beds
      in a transwell assay. This effect was abolished by neutralizing CCL19 or CCL21.
      These data suggest that graft site inflammation increases the expression of CCR7
      ligands in the DLNs, which promote mature DC homing and allorejection.
      CONCLUSIONS: We conclude that the graft site microenvironment plays a critical
      role in alloimmunity by determining DC trafficking through the CCR7-CCL19/21
      axis.

PMID- 27031840
TI  - The Relationship of the Clinical Disc Margin and Bruch's Membrane Opening in
      Normal and Glaucoma Subjects.
AB  - PURPOSE: We tested the hypotheses that the mismatch between the clinical disc
      margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA)
      and is affected by the presence of glaucoma. METHODS: A total of 45 normal eyes
      (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent
      radial optic nerve head (ONH) imaging with spectral domain optical coherence
      tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc
      margin were marked on radial scans and optic disc photographs, and were
      coregistered with custom software. The main outcome measure was the difference
      between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a
      function of BMOA and diagnosis. Multivariate regression analyses were used to
      explore the influence of glaucoma and BMOA on the mismatch. RESULTS: Global CDA
      was larger than BMOA in both groups but the difference was statistically
      significant only in the normal group (1.98 +/- 0.37 vs. 1.85 +/- 0.45 mm2, P =
      0.02 in the normal group; 1.96 +/- 0.38 vs. 1.89 +/- 0.56 mm2, P = 0.08 in the
      glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P
      = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized
      CDA-BMOA difference decreased with increasing BMOA in both groups (P < 0.001).
      Presence or severity of glaucoma did not affect the CDA-BMOA difference (P >
      0.14). CONCLUSIONS: Clinical disc area was larger than BMOA in normal and
      glaucoma eyes but reached statistical significance only in the former group. The
      CDA-BMOA mismatch diminished with increasing BMOA but was not affected by
      presence of glaucoma. These findings have important clinical implications
      regarding clinical evaluation of the ONH.

PMID- 27031841
TI  - Depth Perception and Grasp in Central Field Loss.
AB  - PURPOSE: We set out to determine whether individuals with central field loss
      benefit from using two eyes to perform a grasping task. Specifically, we tested
      the hypothesis that this advantage is correlated with coarse stereopsis, in
      addition to binocular summation indices of visual acuity, contrast sensitivity,
      and binocular visual field. METHODS: Sixteen participants with macular
      degeneration and nine age-matched controls placed pegs on a pegboard, while their
      eye and hand movements were recorded. Importantly, the pegboard was placed near
      eye height, to minimize the contribution of monocular cues to peg position. All
      participants performed this task binocularly and monocularly. Before the
      experiment, we performed microperimetry to determine the profile of field loss in
      each eye and the locations of eccentric fixation (if applicable). In addition, we
      measured both acuity and contrast sensitivity monocularly and binocularly, and
      stereopsis by using both a RanDot test and a custom stereo test. RESULTS: Peg
      placement time was significantly shorter and participants made significantly
      fewer errors with binocular than with monocular viewing in both the patient and
      control groups. Among participants with measurable stereopsis, binocular
      advantage in peg-placement time was significantly correlated with stereoacuity
      (rho = -0.78; P = 0.003). In patients without measurable stereopsis, the
      binocular advantage was related significantly to the overlap in the scotoma
      between the two eyes (rho = -0.81; P = 0.032). CONCLUSIONS: The high correlation
      between grasp performance and stereoacuity indicates that coarse stereopsis may
      benefit tasks of daily living for individuals with central field loss.

PMID- 27031843
TI  - Geographic Atrophy and Activity of Neovascularization in Retinal Angiomatous
      Proliferation.
AB  - PURPOSE: To investigate the association between geographic atrophy (GA) and
      neovascular activity in retinal angiomatous proliferation (RAP) during anti-VEGF
      treatment. METHODS: Ninety-one RAP eyes (74 patients) treated with anti-VEGF on
      an as-needed basis for at least 3 years were evaluated. Development of GA, area
      of GA, and injection numbers were assessed. RESULTS: Eighteen eyes that developed
      fibrous scar or massive hemorrhage were excluded. Forty-four eyes (60%) developed
      GA (GA group), and 29 eyes (40%) did not develop GA (non-GA group) at year 3. The
      mean injection number continuously decreased in the GA group (5.1, 3.1, and 1.9
      at years 1, 2, and 3, respectively, P < 0.01, < 0.01), but did not decrease at
      year 3 in the non-GA group (4.6, 3.5, and 3.3 at years 1, 2, and 3, respectively,
      P < 0.01, = 0.64). In both groups, best-corrected visual acuity improved
      significantly at year 1 and declined to baseline level at year 3. During the
      entire follow-up (mean of 48.5 months), 57 eyes developed GA. In those eyes,
      number of injections per year before and after the development of GA was 4.5 and
      2.1 (P < 0.01), and showed continuous decline after GA development as the area of
      GA progressed at a rate of 1.85 mm2 per year. CONCLUSIONS: The activity of RAP
      lesion requiring anti-VEGF treatment diminished as GA developed and progressed.
      Identification of GA and its progression provides further information to tailor
      anti-VEGF treatment for each patient.

PMID- 27031842
TI  - Sox2-Deficient Muller Glia Disrupt the Structural and Functional Maturation of
      the Mammalian Retina.
AB  - PURPOSE: Muller glia (MG), the principal glial cells of the vertebrate retina,
      display quiescent progenitor cell characteristics. They express key progenitor
      markers, including the high mobility group box transcription factor SOX2 and
      maintain a progenitor-like morphology. In the embryonic and mature central
      nervous system, SOX2 maintains neural stem cell identity. However, its function
      in committed Muller glia has yet to be determined. METHODS: We use inducible, MG
      specific genetic ablation of Sox2 in vivo at the peak of MG genesis to analyze
      its function in the maturation of murine MG and effects on other cells in the
      retina. Histologic and functional analysis of the Sox2-deficient retinas is
      conducted at key points in postnatal development. RESULTS: Ablation of Sox2 in
      the postnatal retina results in disorganization of MG processes in the inner
      plexiform layer and mislocalized cell bodies in the nuclear layers. This
      disorganization is concurrent with a thinning of the neural retina and disruption
      of neuronal processes in the inner and outer plexiform layers. Functional
      analysis by electroretinography reveals a decrease in the b-wave amplitude.
      Disruption of MG maturation due to Sox2 ablation therefore negatively affected
      the function of the retina. CONCLUSIONS: These results demonstrate a novel role
      for SOX2 in glial process outgrowth and adhesion, and provide new insights into
      the essential role Muller glia play in the development of retinal
      cytoarchitecture. Prior to this work, SOX2 was known to have a primary role in
      determining cell fate. Our experiments bypass cell fate conversion to establish a
      new role for SOX2 in a committed cell lineage.

PMID- 27031844
TI  - Proposal of Ancylothrix gen. nov., a new genus of Phormidiaceae (Cyanobacteria,
      Oscillatoriales) based on a polyphasic approach.
AB  - During a study about the diversity of Phormidioideae (Phormidiaceae,
      Oscillatoriales) in Brazil, seven strains from southern and southeastern regions
      were isolated in monospecifc cultures and submitted to polyphasic evaluation
      (morphological, ecological, cytological and molecular studies). The populations
      studied were found to be morphologically similar to Kamptonema (filaments
      narrowed and bent at the end) and cytologically different (thylakoids'
      arrangement - radial distribution in Brazilian strains and parietal distribution
      in Kamptonema). The original habitats were very diverse among the Brazilian
      strains (freshwater, wet soil and barks of trees). Phylogenetic analysis based on
      16S rRNA gene sequences revealed that the strains were placed together in a very
      distinctive and highly supported clade. Thus, the set of characteristics of the
      strains resulted in the recognition of the new genus Ancylothrix Martins et
      Branco gen. nov. with two species [Ancylothrix rivularis gen. nov., sp. nov.
      (type species) and Ancylothrix terrestris sp. nov.], distinguishable by
      differences in genetic and ecological characteristics and described under the
      provisions of the International Code of Nomenclature for algae, fungi and plants.
      Secondary structures of D1-D1', box-B and V3 regions were conserved in A.
      rivularis gen. nov. sp. nov. and more variable in A. terrestris sp. nov. 

PMID- 27031845
TI  - Determining Maximum Glycolytic Capacity Using Extracellular Flux Measurements.
AB  - Measurements of glycolytic rate and maximum glycolytic capacity using
      extracellular flux analysis can give crucial information about cell status and
      phenotype during normal operation, development of pathology, differentiation, and
      malignant transformation. They are also of great use when assessing the effects
      of chemical or drug treatments. Here, we experimentally define maximum glycolytic
      capacity, demonstrate how it differs from glycolytic rate, and provide a protocol
      for determining the basal glycolytic rate and maximum glycolytic capacity in
      cells using extracellular flux measurements. The results illustrate the power of
      extracellular flux analysis to describe the energetics of adherent cells in
      culture in a fully quantitative way. 

PMID- 27031846
TI  - Life Course Socioeconomic Position: Associations with Cardiac Structure and
      Function at Age 60-64 Years in the 1946 British Birth Cohort.
AB  - Although it is recognized that risks of cardiovascular diseases associated with
      heart failure develop over the life course, no studies have reported whether life
      course socioeconomic inequalities exist for heart failure risk. The Medical
      Research Council's National Survey of Health and Development was used to
      investigate associations between occupational socioeconomic position during
      childhood, early adulthood and middle age and measures of cardiac structure [left
      ventricular (LV) mass index and relative wall thickness (RWT)] and function
      [systolic: ejection fraction (EF) and midwall fractional shortening (mFS);
      diastolic: left atrial (LA) volume, E/A ratio and E/e' ratio)]. Different life
      course models were compared with a saturated model to ascertain the nature of the
      relationship between socioeconomic position across the life course and each
      cardiac marker. Findings showed that models where socioeconomic position
      accumulated over multiple time points in life provided the best fit for 3 of the
      7 cardiac markers: childhood and early adulthood periods for the E/A ratio and
      E/e' ratio, and all three life periods for LV mass index. These associations were
      attenuated by adjustment for adiposity, but were little affected by adjustment
      for other established or novel cardio-metabolic risk factors. There was no
      evidence of a relationship between socioeconomic position at any time point and
      RWT, EF, mFS or LA volume index. In conclusion, socioeconomic position across
      multiple points of the lifecourse, particularly earlier in life, is an important
      determinant of some measures of LV structure and function. BMI may be an
      important mediator of these associations. 

PMID- 27031847
TI  - Vaccine-associated enhanced respiratory disease is influenced by haemagglutinin
      and neuraminidase in whole inactivated influenza virus vaccines.
AB  - Multiple subtypes and many antigenic variants of influenza A virus (IAV) co
      circulate in swine in the USA, complicating effective use of commercial vaccines
      to control disease and transmission. Whole inactivated virus (WIV) vaccines may
      provide partial protection against IAV with substantial antigenic drift, but have
      been shown to induce vaccine-associated enhanced respiratory disease (VAERD) when
      challenged with an antigenic variant of the same haemagglutinin (HA) subtype.
      This study investigated the role the immune response against HA, neuraminidase
      (NA) and nucleoprotein (NP) may play in VAERD by reverse engineering vaccine and
      challenge viruses on a common backbone and using them in a series of
      vaccination/challenge trials. Mismatched HA between vaccine and challenge virus
      was necessary to induce VAERD. However, vaccines containing a matched NA
      abrogated the VAERD phenomenon induced by the HA mismatch and this was correlated
      with NA-inhibiting (NI) antibodies. Divergence between the two circulating swine
      N2 lineages (92 % identity) resulted in a loss of NI cross-reactivity and also
      resulted in VAERD with the mismatched HA. The NP lineage selected for use in the
      WIV vaccine strains did not affect protection or pathology. Thus the combination
      of HA and NA in the vaccine virus strains played a substantial role in vaccine
      protection versus immunopathology, suggesting that vaccines that target the HA
      protein alone could be more prone to VAERD due to the absence of cross-protective
      NI antibodies.

PMID- 27031848
TI  - Correlations of survival with progression-free survival, response rate, and
      disease control rate in advanced biliary tract cancer: a meta-analysis of
      randomised trials of first-line chemotherapy.
AB  - BACKGROUND: The need to promote novel drug development for advanced biliary tract
      cancer (ABTC) has emphasised the importance of determining whether various
      efficacy end points can act as surrogates for overall survival (OS). METHODS: We
      conducted a literature search of randomised trials of first-line chemotherapy for
      ABTC and investigated correlations between efficacy end points and OS using
      weighted linear regression analysis. The ratios of the median OS, median
      progression-free survival (PFS), response rate, and disease control rate in each
      trial were used to summarise treatment effects. The surrogate threshold effect
      (STE), which was the minimum treatment effect on PFS required to predict a non
      zero treatment effect on OS, was calculated. RESULTS: Seventeen randomised trials
      with 36 treatment arms were identified, and a sample size of 2148 patients with
      19 paired arms was analysed. The strongest correlation between all evaluated
      efficacy end points was observed between median OS and median PFS ratios
      (r(2)=0.66). In trials with gemcitabine-containing therapies and targeted agents,
      the r(2)-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81
      for trials with gemcitabine-containing therapies, and was not calculated for
      trials with targeted agents. CONCLUSIONS: The median PFS ratio correlated well
      with the median OS ratio, and may be useful for planning a clinical trial for
      novel drug development.

PMID- 27031849
TI  - Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer
      models.
AB  - BACKGROUND: The natural polyphenol myricetin induces cell cycle arrest and
      apoptosis in preclinical cancer models. We hypothesised that myricetin-derived
      flavonoids with enhanced redox properties, improved cell uptake and mitochondrial
      targeting might have increased potential as antitumour agents. METHODS: We
      studied the effect of a second-generation flavonoid analogue Oncamex in a panel
      of seven breast cancer cell lines, applying western blotting, gene expression
      analysis, fluorescence microscopy and immunohistochemistry of xenograft tissue to
      investigate its mechanism of action. RESULTS: Proliferation assays showed that
      Oncamex treatment for 8 h reduced cell viability and induced cytotoxicity and
      apoptosis, concomitant with increased caspase activation. Microarray analysis
      showed that Oncamex was associated with changes in the expression of genes
      controlling cell cycle and apoptosis. Fluorescence microscopy showed the
      compound's mitochondrial targeting and reactive oxygen species-modulating
      properties, inducing superoxide production at concentrations associated with
      antiproliferative effects. A preliminary in vivo study in mice implanted with the
      MDA-MB-231 breast cancer xenograft showed that Oncamex inhibited tumour growth,
      reducing tissue viability and Ki-67 proliferation, with no signs of untoward
      effects on the animals. CONCLUSIONS: Oncamex is a novel flavonoid capable of
      specific mitochondrial delivery and redox modulation. It has shown antitumour
      activity in preclinical models of breast cancer, supporting the potential of this
      prototypic candidate for its continued development as an anticancer agent.

PMID- 27031850
TI  - Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the
      randomised phase III AVAGAST trial.
AB  - BACKGROUND: In the phase III AVAGAST trial, the addition of bevacizumab to
      chemotherapy improved progression-free survival (PFS) but not overall survival
      (OS) in patients with advanced gastric cancer. We studied the role of
      Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and
      resistance to antiangiogenic treatment, as a biomarker. METHODS: Previously
      untreated, advanced gastric cancer patients were randomly assigned to receive
      bevacizumab (n=387) or placebo (n=387) in combination with chemotherapy. Plasma
      collected at baseline and at progression was analysed by ELISA. The role of Ang-2
      as a prognostic and a predictive biomarker of bevacizumab efficacy was studied
      using a Cox proportional hazards model. Logistic regression analysis was applied
      for correlations with metastasis. RESULTS: Median baseline plasma Ang-2 levels
      were lower in Asian (2143 pg ml(-1)) vs non-Asian patients (3193 pg ml(-1)),
      P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic
      marker for OS but did not predict bevacizumab efficacy alone or in combination
      with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver
      metastasis (LM) at any time: Odds ratio per 1000 pg ml(-1) increase: 1.19; 95% CI
      1.10-1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13-1.64; P=0.0010 (Asians).
      CONCLUSIONS: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in
      advanced gastric cancer strongly associated with LM. Differences in Ang-2
      mediated vascular response may, in part, account for outcome differences between
      Asian and non-Asian patients; however, data have to be further validated. Ang-2
      is a promising drug target in gastric cancer.

PMID- 27031851
TI  - Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in
      metastatic melanoma patients.
AB  - BACKGROUND: Current approaches for treating metastatic malignant melanoma (MM)
      are not effective enough and are associated with serious adverse events. Due to
      its immunogenicity, melanoma is an attractive target for immunostimulating
      therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy
      was evaluated in patients with MM. METHODS: AdCD40L is an adenovirus carrying the
      gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six
      patients received four weekly intratumoral AdCD40L injections. Next, nine
      patients received low-dose cyclophosphamide conditioning before the first and
      fourth AdCD40L injection. The blood samples were collected at multiple time
      points for chemistry, haematology and immunology evaluations. Radiology was
      performed at enrolment and repeated twice after the treatment. RESULTS: AdCD40L
      was safe with mild transient reactions. No objective responses were recorded by
      MRI, however, local and distant responses were seen on FDG-PET. The overall
      survival at 6 months was significantly better when cyclophosphamide was added to
      AdCD40L. The patients with the best survival developed the highest levels of
      activated T cells and experienced a pronounced decrease of intratumoral IL8.
      CONCLUSIONS: AdCD40L therapy for MM was well tolerated. Local and distant
      responses along with better survival in the low-dose cyclophosphamide group are
      encouraging.

PMID- 27031852
TI  - The clinical implications of gene mutations in chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is a molecularly heterogeneous disease as
      revealed by recent genomic studies. Among genetic lesions that are recurrent in
      CLL, few clinically validated prognostic markers, such as TP53 mutations and 17p
      deletion, are available for the use in clinical practice to guide treatment
      decisions. Recently, several novel molecular markers have been identified in CLL.
      Though these mutations have not yet gained the qualification of predictive
      factors for treatment tailoring, they have shown to be promising to refine the
      prognostic stratification of patients. The introduction of targeted drugs is
      changing the genetics of CLL, and has disclosed the acquisition of previously
      unexpected drug resistant mutations in signalling pathway genes. Ultra-deep next
      generation sequencing has allowed to reach deep levels of resolution of the
      genetic portrait of CLL providing a precise definition of its subclonal genetic
      architecture. This approach has shown that small subclones harbouring drug
      resistant mutations anticipate the development of a chemorefractory phenotype.
      Here we review the recent advances in the definition of the genomic landscape of
      CLL and the ongoing research to characterise the clinical implications of old and
      new molecular lesions in the setting of both conventional chemo-immunotherapy and
      targeted drugs. 

PMID- 27031853
TI  - Acute changes in liver tumour perfusion measured non-invasively with arterial
      spin labelling.
AB  - BACKGROUND: Non-invasive measures of tumour vascular perfusion are desirable, in
      order to assess response to vascular targeting (or modifying) therapies. In this
      study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was
      investigated to measure acute changes in perfusion of colorectal cancer in the
      liver, in response to vascular disruption therapy with OXi4503. METHODS: SW1222
      and LS174T tumours were established in the liver of MF1 nu/nu mice via
      intrasplenic injection. Perfusion and R2(*) MRI measurements were acquired with
      an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg(-1)
      OXi4503. RESULTS: A significant decrease in SW1222 tumour perfusion was observed
      (-43+/-33%, P<0.005). LS174T tumours had a significantly lower baseline level of
      perfusion. Intrinsic susceptibility MRI showed a significant increase in R2(*) in
      LS174T tumours (28+/-25%, P<0.05). An association was found between the change in
      tumour perfusion and the proximity to large vessels, with pre-treatment blood
      flow predictive of subsequent response. Histological evaluation confirmed the
      onset of necrosis and evidence of heterogeneous response between tumour deposits.
      CONCLUSIONS: Hepatic ASL-MRI can detect acute response to targeted tumour
      vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has
      potential for use in a clinical setting.

PMID- 27031854
TI  - Randomised phase III trial of FEC120 vs EC-docetaxel in patients with high-risk
      node-positive primary breast cancer: final survival analysis of the ADEBAR study.
AB  - BACKGROUND: Taxane-containing adjuvant chemotherapy has been established as
      standard treatment in node-positive breast cancer. This study compared efficacy
      and tolerability of epirubicin (E)/cyclophosphamide (C) followed by docetaxel
      (Doc) with a dose-dense 5-fluorouracil (F)+E+ C regimen. METHODS: The ADEBAR
      study was a randomised phase III trial for women with primary invasive breast
      cancer and ?4 metastatic axillary lymph nodes (n=1364). Treatment consisted of
      four 21-day cycles of E plus C, followed by four 21-day cycles of Doc (EC-Doc),
      or six 28-day cycles of E plus F plus C (FEC120). RESULTS: Disease-free survival
      (DFS) was similar in the two treatment arms as shown by multivariate Cox
      regression adjusted for other prognostic factors (EC-Doc vs FEC120, hazard ratio
      (HR): 1.087; 95% confidence interval (CI): 0.878-1.346, P=0.444). In addition,
      there was no significant difference in overall survival (OS) between the two
      groups (HR: 0.974; 95% CI: 0.750-1.264, P=0.841). Haematologic toxicity was more
      common in FEC120 recipients; non-haematologic toxicities occurred more frequently
      in the EC-Doc arm. The serious adverse event rate was significantly higher in the
      FEC120 group (29.7% vs 22.5%). CONCLUSIONS: EC-Doc provides a feasible and
      effective alternative therapy option to FEC120 with a different safety profile in
      this high-risk breast cancer cohort.

PMID- 27031856
TI  - C3-PRO: Connecting ResearchKit to the Health System Using i2b2 and FHIR.
AB  - A renewed interest by consumer information technology giants in the healthcare
      domain is focused on transforming smartphones into personal health data storage
      devices. With the introduction of the open source ResearchKit, Apple provides a
      framework for researchers to inform and consent research subjects, and to readily
      collect personal health data and patient reported outcomes (PRO) from distributed
      populations. However, being research backend agnostic, ResearchKit does not
      provide data transmission facilities, leaving research apps disconnected from the
      health system. Personal health data and PROs are of the most value when presented
      in context along with health system data. Our aim was to build a toolchain that
      allows easy and secure integration of personal health and PRO data into an open
      source platform widely adopted across 140 academic medical centers. We present C3
      PRO: the Consent, Contact, and Community framework for Patient Reported Outcomes.
      This open source toolchain connects, in a standards-compliant fashion, any
      ResearchKit app to the widely-used clinical research infrastructure Informatics
      for Integrating Biology and the Bedside (i2b2). C3-PRO leverages the emerging
      health data standard Fast Healthcare Interoperability Resources (FHIR). 

PMID- 27031855
TI  - Soluble tumour necrosis factor receptor type II and survival in colorectal
      cancer.
AB  - BACKGROUND: Chronic inflammation may play a role in colorectal cancer (CRC)
      pathogenesis. The relationship between soluble tumour necrosis factor receptor
      type II (sTNF-RII) and survival among CRC patients is not well defined. METHODS:
      We prospectively evaluated the association between pre-diagnosis plasma levels of
      sTNF-RII and mortality in 544 CRC patients from the Nurses' Health Study and
      Health Professionals Follow-Up Study diagnosed from 1990 to 2010. Primary and
      secondary end points were overall and CRC-specific mortality, respectively. Cox
      proportional hazards models were used to calculate multivariate hazard ratios for
      mortality. RESULTS: Higher sTNF-RII levels were significantly associated with
      increased overall mortality (multivariate HR=1.48, 95% CI 1.02-2.16, P
      trend=0.006), but not with CRC-specific mortality (HR=1.23, 95% CI 0.72-2.08, P
      trend=0.34). In subgroup analyses, among regular aspirin users, those with higher
      sTNF-RII levels had an adjusted HR of 0.52 (95% CI 0.20-1.33) for overall
      mortality compared with those with lower sTNF-RII levels, whereas among
      nonregular aspirin users the adjusted HR was 2.26 (95% CI 1.23-4.01, P for
      interaction=0.53). CONCLUSIONS: Among CRC patients, higher sTNF-RII levels are
      associated with a significant increase in overall mortality, but not CRC-specific
      mortality. The role of inflammation and anti-inflammatory medications in survival
      of CRC patients warrants further exploration.

PMID- 27031857
TI  - In Silico and Fluorescence In Situ Hybridization Mapping Reveals Collinearity
      between the Pennisetum squamulatum Apomixis Carrier-Chromosome and Chromosome 2
      of Sorghum and Foxtail Millet.
AB  - Apomixis, or clonal propagation through seed, is a trait identified within
      multiple species of the grass family (Poaceae). The genetic locus controlling
      apomixis in Pennisetum squamulatum (syn Cenchrus squamulatus) and Cenchrus
      ciliaris (syn Pennisetum ciliare, buffelgrass) is the apospory-specific genomic
      region (ASGR). Previously, the ASGR was shown to be highly conserved but inverted
      in marker order between P. squamulatum and C. ciliaris based on fluorescence in
      situ hybridization (FISH) and varied in both karyotype and position of the ASGR
      on the ASGR-carrier chromosome among other apomictic Cenchrus/Pennisetum species.
      Using in silico transcript mapping and verification of physical positions of some
      of the transcripts via FISH, we discovered that the ASGR-carrier chromosome from
      P. squamulatum is collinear with chromosome 2 of foxtail millet and sorghum
      outside of the ASGR. The in silico ordering of the ASGR-carrier chromosome
      markers, previously unmapped in P. squamulatum, allowed for the identification of
      a backcross line with structural changes to the P. squamulatum ASGR-carrier
      chromosome derived from gamma irradiated pollen. 

PMID- 27031858
TI  - Correction: Changes in Soil Microbial Community Structure Influenced by
      Agricultural Management Practices in a Mediterranean Agro-Ecosystem.

PMID- 27031859
TI  - Cognitive Load and Self-Determination Theories Applied to E-Learning: Impact on
      Students' Participation and Academic Performance.
AB  - BACKGROUND: Emergency clerkships expose students to a stressful environment that
      require multiple tasks, which may have a direct impact on cognitive load and
      motivation for learning. To address this challenge, Cognitive Load Theory and
      Self Determination Theory provided the conceptual frameworks to the development
      of a Moodle-based online Emergency Medicine course, inspired by real clinical
      cases. METHODS: Three consecutive classes (2013-2015) of sixth-year medical
      students (n = 304) participated in the course, during a curricular and
      essentially practical emergency rotation. "Virtual Rounds" provided weekly
      virtual patients in narrative format and meaningful schemata to chief complaints,
      in order to simulate real rounds at Emergency Unit. Additional activities such as
      Extreme Decisions, Emergency Quiz and Electrocardiographic challenge offered
      different views of emergency care. Authors assessed student's participation and
      its correlation with their academic performance. A survey evaluated students'
      opinions. Students graduating in 2015 answered an online questionnaire to
      investigate cognitive load and motivation. RESULTS: Each student produced 1965
      pageviews and spent 72 hours logged on. Although Clinical Emergency rotation has
      two months long, students accessed the online course during an average of 5.3
      months. Virtual Rounds was the most accessed activity, and there was positive
      correlations between the number of hours logged on the platform and final grades
      on Emergency Medicine. Over 90% of students felt an improvement in their clinical
      reasoning and considered themselves better prepared for rendering Emergency care.
      Considering a Likert scale from 1 (minimum load) to 7 (maximum load), the scores
      for total cognitive load were 4.79+/-2.2 for Virtual Rounds and 5.56+/-1.96 for
      real medical rounds(p<0,01). CONCLUSIONS: A real-world inspired online course,
      based on cognitive and motivational conceptual frameworks, seems to be a strong
      tool to engage students in learning. It may support them to manage the cognitive
      challenges involved in clinical care and increase their motivation for learning.

PMID- 27031860
TI  - Parkinson's Inside Out.

PMID- 27031861
TI  - Impulse Control Disorders - The Continuum Hypothesis.
AB  - The group Parkinson Inside Out is composed of health professionals and academic
      researchers who have been diagnosed with Parkinson's Disease. In our discussions
      we try to make use of both our inside perspective as patients, and our outside
      perspective as professionals. In this paper, we apply the two perspectives to the
      Impulse Control Disorders. These impulsive behaviour patterns are thought to be
      relatively uncommon side effects of some of the medication used in dopamine
      replacement therapy. The phenomenon is usually described as relatively rare
      (<15%), and mainly confined to patients with special vulnerabilities. In
      contrast, we propose that having some problems with controlling impulses is a
      very common experience for patients undergoing dopamine replacement therapy. They
      result from difficulties in decision making engendered by variations in dopamine
      accessibility in the reward centre of the brain. Only in a minority do the
      consequences grow to the damaging proportions of a disorder, but most patients
      are probably affected to some degree. Seeing, and measuring, decision
      difficulties as a continuous dimension, rather than as a discrete category,
      brings increased possibilities for early detection and continuous monitoring.
      With reliable measures of the propensity for impulsive decision making, it may
      become possible to both reap the benefits and avoid the dangers of the dopamine
      agonists. We point to ways of empirically testing our continuity hypothesis. 

PMID- 27031862
TI  - Feasibility of a Randomized Controlled Trial of Self-Administered Acupressure for
      Symptom Management in Older Adults with Knee Osteoarthritis.
AB  - OBJECTIVES: To assess the feasibility of a study to evaluate the efficacy of self
      administered acupressure in pain and related symptom management for older people
      with symptomatic knee osteoarthritis. Feasibility with regard to (1) sample
      recruitment and retention, (2) treatment fidelity and adherence, and (3)
      tolerability and adverse events was examined. METHODS: The study was a randomized
      controlled trial. Community-living older adults were recruited and randomly
      assigned to one of three groups: verum acupressure, sham acupressure, and usual
      care. Participants in the first two groups learned their respective acupressure
      protocol during their first center visit and from a set of materials. They were
      asked to practice the protocol at home once daily, 5 days a week, for 8 weeks.
      Participants attended three center visits and received weekly phone calls from a
      research assistant in an 8-week study period. Both quantitative and qualitative
      data collected from center visits and weekly phone calls were used to examine
      study feasibility. RESULTS: A total of 150 participants (mean age, 73 years; 38%
      men) were enrolled; 83% completed all three center visits. Among those assigned
      to verum and sham acupressure groups, 94% passed a fidelity check at the second
      visit, more than 80% reported performing self-administered acupressure as
      instructed most of the time, and about 10% reported discomfort from performing
      the acupressure. Thirty adverse events were reported; most were related to pre
      existing health conditions. CONCLUSIONS: It is feasible to conduct a study of
      self-administered acupressure for symptom management in community-living older
      adults with knee osteoarthritis, although sample recruitment may be challenging.

PMID- 27031864
TI  - Mechanisms of MicroRNA Deregulation and MicroRNA Targets in Gastric Cancer.
AB  - Gastric cancer is a genetically heterogeneous disease that causes cancer-related
      deaths worldwide. Although many studies on this disease have been performed, the
      molecular mechanisms of gastric tumorigenesis, invasion, and metastasis have
      still not been identified. MicroRNAs (miRNAs) are endogenously coded small RNA
      molecules, 18-25 nucleotides in length, that regulate gene expression at the post
      transcriptional level. They are required for physiological activities in the
      cell, including development, proliferation, differentiation, and apoptosis.
      Research has now indicated their importance in carcinogenesis, with miRNA
      profiling revealing differences in the tumor and the normal tissue in several
      cancers. This difference in the expression pattern might lead to disrupted
      regulation of genes such as tumor suppressor genes and proto-oncogenes that are
      involved in cell cycle control, proliferative pathways, apoptosis, and metastasis
      in gastric carcinogenesis. Genes encoding miRNAs have been characterized as novel
      proto-oncogenes and tumor-suppressor genes based on findings that these miRNAs
      control malignant phenotypes. miRNA deregulation promotes cell-cycle progression,
      confers resistance to apoptosis, and enhances invasiveness and metastasis.
      Deregulated miRNAs affect the regulation of their target genes. Knowing the
      targets of miRNAs is of great importance for identifying the molecular mechanisms
      behind gastric carcinogenesis and forms the focus of this review. 

PMID- 27031863
TI  - Quantitative Modeling of the Alternative Pathway of the Complement System.
AB  - The complement system is an integral part of innate immunity that detects and
      eliminates invading pathogens through a cascade of reactions. The destructive
      effects of the complement activation on host cells are inhibited through
      versatile regulators that are present in plasma and bound to membranes.
      Impairment in the capacity of these regulators to function in the proper manner
      results in autoimmune diseases. To better understand the delicate balance between
      complement activation and regulation, we have developed a comprehensive
      quantitative model of the alternative pathway. Our model incorporates a system of
      ordinary differential equations that describes the dynamics of the four steps of
      the alternative pathway under physiological conditions: (i) initiation (fluid
      phase), (ii) amplification (surfaces), (iii) termination (pathogen), and (iv)
      regulation (host cell and fluid phase). We have examined complement activation
      and regulation on different surfaces, using the cellular dimensions of a
      characteristic bacterium (E. coli) and host cell (human erythrocyte). In
      addition, we have incorporated neutrophil-secreted properdin into the model
      highlighting the cross talk of neutrophils with the alternative pathway in
      coordinating innate immunity. Our study yields a series of time-dependent
      response data for all alternative pathway proteins, fragments, and complexes. We
      demonstrate the robustness of alternative pathway on the surface of pathogens in
      which complement components were able to saturate the entire region in about 54
      minutes, while occupying less than one percent on host cells at the same time
      period. Our model reveals that tight regulation of complement starts in fluid
      phase in which propagation of the alternative pathway was inhibited through the
      dismantlement of fluid phase convertases. Our model also depicts the intricate
      role that properdin released from neutrophils plays in initiating and propagating
      the alternative pathway during bacterial infection. 

PMID- 27031865
TI  - Understanding of Constipation Symptoms and the Diagnosis and Management of
      Constipation in Chinese Physicians.
AB  - BACKGROUND AND AIMS: Although a range of guidelines for the diagnosis and
      treatment of chronic constipation has been carried out, there was very little
      information about the understanding on constipation. The aim of the present study
      was to estimate the understanding of constipation symptoms and the diagnosis and
      management of constipation by clinical physicians in China. METHODS: Participants
      were physicians and researchers in the field of gastroenterology in China who
      were scheduled to attend the National Conference on gastrointestinal motility
      (Constipation). Based on the recommendation of the Rome Foundation Board, the
      self-reported questionnaire was constructed. FINDINGS: Although most of the
      opinions on symptoms of constipation were consistent, there were still some
      differences. Opinions on the Bristol stool form during constipation were
      discordant, 34% of the doctors thought that it was type 1 and type 2, while 46%of
      the doctors suggested that type 3 should also be considered constipation. There
      was no significant difference between them (P = 0.05); We investigated the
      interpretation on the duration of defecation prolonged, 27% of the doctors
      suggested it should be longer than 10 minutes, 22% of the doctors suggested it
      should be longer than 20 minutes, and other 22% of the doctors suggested it
      should be time of defecation became longer compared to previously bowel habits,
      there was no significant difference among them (P = 0.38).Only 36% of the doctors
      thought that psychotherapy was most important in the treatment of severe
      constipation, while 37% of the doctors thought that medication treatment was most
      important in the treatment of severe constipation, there was no significant
      difference between them (P = 0.895). CONCLUSION: We were able to obtain valuable
      information about current views on symptoms of constipation and the diagnosis and
      treatment of constipation among Chinese doctors. Although most of the opinions
      were consistent there were still some differences. This study indicated that in
      practice in China there was a need for further study on the role of constipation
      symptoms and there may also be a need for better establishment of consensus
      guidelines for constipation.

PMID- 27031866
TI  - Protein engineering strategies with potential applications for altering
      clinically relevant cellular pathways at the protein level.
AB  - All diseases can be fundamentally viewed as the result of malfunctioning cellular
      pathways. Protein engineering offers the potential to develop new tools that will
      allow these dysfunctional pathways to be better understood, in addition to
      potentially providing new routes to restore proper function. Here we discuss
      different approaches that can be used to change the intracellular activity of a
      protein by intervening at the protein level: targeted protein sequestration,
      protein recruitment, protein degradation, and selective inhibition of binding
      interfaces. The potential of each of these tools to be developed into effective
      therapeutic treatments will also be discussed, along with any major barriers that
      currently block their translation into the clinic.

PMID- 27031868
TI  - A General Copper-Catalyzed Vinylic Halogen Exchange Reaction.
AB  - An efficient and general system for the halogen exchange reaction in alkenyl
      halides has been developed. Upon reaction with catalytic amounts of copper iodide
      and trans-N,N'-dimethylcyclohexane-1,2-diamine in the presence of
      tetramethylammonium chloride or bromide, a wide range of easily accessible
      alkenyl iodides can be smoothly transformed to their far less available
      chlorinated and brominated derivatives in excellent yields and with full
      retention of the double bond geometry. This reaction also enables the
      chlorination of bromoalkenes and could be extended to the use of gem
      dibromoalkenes. 

PMID- 27031867
TI  - Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira
      Infection.
AB  - Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The
      main reservoirs of Leptospira, which presents an asymptomatic infection, are wild
      rodents, including the brown rat (Rattus norvegicus). Experimental studies of the
      mechanisms of its renal colonization in rats have previously used an
      intraperitoneal inoculation route. However, knowledge of rat-rat transmission
      requires the use of a natural route of inoculation, such as a mucosal or
      subcutaneous route. We investigated for the first time the effects of
      subcutaneous and mucosal inoculation routes compared to the reference
      intraperitoneal route during Leptospira infection in adult rats. Infection
      characteristics were studied using Leptospira renal isolation, serology, and
      molecular and histological analyses. Leptospira infection was asymptomatic using
      each inoculation route, and caused similar antibody production regardless of
      renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5
      out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and
      subcutaneous inoculation routes, respectively. Thus, among the natural infection
      routes studied, mucosal inoculation was more efficient for renal colonization
      associated with urinary excretion than the subcutaneous route and induced a
      slower-progressing infection than the intraperitoneal route. These results can
      facilitate understanding of the infection modalities in rats, unlike the
      epidemiological studies conducted in wild rats. Future studies of other natural
      inoculation routes in rat models will increase our knowledge of rat-rat disease
      transmission and allow the investigation of infection kinetics. 

PMID- 27031869
TI  - Leveraging Health-Related Quality of Life in Population Health Management: The
      Case for Healthy Days.
AB  - Measuring population health with morbidity and mortality data, often collected at
      the site of care, fails to capture the individual's perspective on health and
      well-being. Because health happens outside the walls of medical facilities, a
      holistic and singular measure of health that can easily be captured for an entire
      population could aid in understanding the well-being of communities. This paper
      postulates that Healthy Days, a health-related quality of life measure developed
      and validated by the Centers for Disease Control and Prevention, is an ideal
      survey instrument to advance population health. A systematic literature review
      was conducted and revealed a strong evidence base using Healthy Days with
      significant correlations to chronic disease conditions. Building on the
      literature base and experience, methods for analyzing Healthy Days data are
      discussed, including stratified sampling techniques, statistical measures to
      account for variance, and modeling techniques for skewed distributions. Using
      such analytic techniques, Healthy Days has been used extensively in national
      health surveillance. As the health care system faces increasing costs and
      constrained resources, the Healthy Days survey instrument can be used to inform
      public policies and allocate health service resources. Because Healthy Days
      captures broad dimensions of health from the individual's perspective, it is a
      simple way to holistically measure the health and well-being of a population and
      its trend over time. Expanded use of Healthy Days can aid population health
      managers and contribute to the understanding of the broader determinants of the
      nation's and individual community's health and aid in evaluating progress toward
      health goals.

PMID- 27031870
TI  - Controlled Exfoliation of MoS2 Crystals into Trilayer Nanosheets.
AB  - The controlled exfoliation of transition metal dichalcogenides (TMDs) into
      pristine single- or few-layer nanosheets remains a significant barrier to
      fundamental studies and device applications of TMDs. Here we report a novel
      strategy for exfoliating crystalline MoS2 into suspensions of nanosheets with
      retention of the semiconducting 2H phase. The controlled reaction of MoS2 with
      substoichiometric amounts n-butyllithium results in intercalation of the edges of
      the crystals, which are then readily exfoliated in a 45 vol % ethanol-water
      solution. Surprisingly, the resulting colloidal suspension of nanosheets was
      found (by electron microscopy and atomic force microscopy) to consist mostly of
      trilayers. The efficiency of exfoliation of the pre-intercalated sample is
      increased by at least 1 order of magnitude relative to the starting MoS2
      microcrystals, with a mass yield of the dispersed nanosheets of 11-15%. 

PMID- 27031871
TI  - Remote ischemic postconditioning protects ischemic brain from injury in rats with
      focal cerebral ischemia/reperfusion associated with suppression of TLR4 and NF-kB
      expression.
AB  - Remote ischemic postconditioning (RIPC) has been proven to be a promising
      protective method for brain damage caused by transient focal ischemia/reperfusion
      (I/R) injury. However, the underlying mechanism of RIPC remains elusive. To
      address whether RIPC protects against brain damage by regulating TLR4 and the NF
      kappaB pathway, focal I/R rat (SD) model induced by 1 h transient middle cerebral
      artery occlusion was used in this study. RIPC treatment was generated by three
      cycles of 10 min occlusion and 10 min release of the bilateral hind femoral
      arteries. The Garcia JH score was used to evaluate neurobehavioral function and
      triphenyltetrazolium chloride staining was used to estimate the infarct size of
      the brain. The expression levels of TLR4 and NF-kappaB were determined by
      quantitative PCR and immunohistochemistry. The results showed that RIPC treatment
      significantly improved neurological deficits and decreased infarct volume.
      Furthermore, it also inhibited the overexpression of TLR4 and NF-kappaB induced
      by middle cerebral artery occlusion reperfusion. Thus, we suggested that RIPC
      might protect ischemic brain against I/R injury in rats by suppressing the
      TLR4/NF-kB pathway. 

PMID- 27031872
TI  - Desensitization of leptin receptors is coincident with the upregulation of
      dopamine-related genes in the prefrontal cortex of adolescent mice.
AB  - We have investigated in adolescent mice the effect of subchronic leptin on (i)
      leptin receptor expression and functionality, and (ii) dopamine-related gene
      expression (tyrosine hydroxylase, Th; dopamine type-1 receptor, Drd1; dopamine
      type-2 receptor, Drd2) within the prefrontal cortex (PFC), which is involved in
      sensory perception of food and reward sensitivity, and the hippocampus, a brain
      area sensitive to food composition and pivotal in learning and memory processes
      related to feeding behaviour. Here, we show that leptin treatment triggered
      leptin resistance both in the hippocampus and in the PFC. In contrast, leptin
      induced the upregulation of dopamine-related genes in the PFC, whereas it failed
      to modify the expression of these genes in the hippocampus. The effect of leptin
      was similar irrespective of the time elapsed since the last leptin administration
      (either 2 or 14 h), indicating that the effect detected was not associated with
      leptin withdrawal. Our data show that leptin receptor desensitization is
      coincident with the upregulation of dopamine-related genes in the PFC of
      adolescent mice undergoing hyperleptinaemia triggered by exogenous leptin. 

PMID- 27031873
TI  - Intrinsic intranasal chemosensory brain networks shown by resting-state
      functional MRI.
AB  - The human brain is organized into functional networks for sensory-motor and
      cognitive processing. Intrinsic networks are detectable in the absence of
      stimulation or task demands, whereas extrinsic networks are detectable when
      stimulated by sensory or cognitive demands. Intranasal chemosensory processing
      relies on two dissociable networks for processing incoming trigeminal and
      olfactory stimulation, but it is not known whether these networks are
      intrinsically organized. The aim of this study was to identify whether brain
      networks for intranasal chemosensory processing are detectable in functional
      connectivity resting-state functional MRI (fMRI). Sixteen healthy adults
      participated in a 5-min resting-state fMRI study. Functional connectivity seeds
      were defined from coordinates that anchor olfactory (i.e. bilateral piriform and
      orbitofrontal cortex) and trigeminal (bilateral anterior insula and cingulate
      cortex) networks in published task activation studies, and the resulting networks
      were thresholded at P less than 0.001. The olfactory network showed extended
      functional connectivity to the thalamus, medial prefrontal cortex, caudate,
      nucleus accumbens, parahippocampal gyrus, and hippocampus. The trigeminal network
      showed extended functional connectivity to the precuneus, thalamus, caudate,
      brainstem, and cerebellum. Both networks overlapped in the thalamus, caudate,
      medial prefrontal cortex, and insula. These results show that brain networks for
      intranasal chemosensory processing are intrinsically organized, not just
      extrinsically instantiated in response to task demands, and resemble networks for
      processing olfactory and trigeminal stimulation. As such, it may be possible to
      study the functional organization and dynamics of the olfactory network in
      resting-state fMRI as well as its implications for aging and disease. 

PMID- 27031874
TI  - Characterization of seizures induced by acute exposure to an organophosphate
      herbicide, glufosinate-ammonium.
AB  - Glufosinate-ammonium (GLA), the active component of a widely used herbicide,
      induces convulsions in rodents and humans. In mouse, intraperitoneal treatment
      with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100%
      mortality within 72 h after treatment. In this context, we characterized GLA
      induced seizures, their histological consequences and the effectiveness of
      diazepam treatment. Epileptic discharges on electroencephalographic recordings
      appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam
      treatment at 6 h immediately stopped the seizures and prevented animal death.
      However, intermittent seizures were recorded on electroencephalogram from 6 h
      after diazepam treatment until 24 h, but had disappeared after 15 days. In our
      model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after
      GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal
      cortices, indicating the activation of the limbic system. In these structures,
      Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering.
      However, astroglial activation was clearly observed at 24 h and 15 days after GLA
      treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative,
      western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA
      expression (PCR quantitative), protein expression (western blot) and enzymatic
      activity were upregulated. In conclusion, our study suggests that GLA-induced
      seizures: (a) involved limbic structures and (b) induced astrocytosis without
      neuronal degeneration as an evidence of a reactive astrocyte beneficial effect
      for neuronal protection. 

PMID- 27031875
TI  - The scarcity heuristic impacts reward processing within the medial-frontal
      cortex.
AB  - Objects that are rare are often perceived to be inherently more valuable than
      objects that are abundant - a bias brought about in part by the scarcity
      heuristic. In the present study, we sought to test whether perception of rarity
      impacted reward evaluation within the human medial-frontal cortex. Here,
      participants played a gambling game in which they flipped rare and abundant
      'cards' on a computer screen to win financial rewards while
      electroencephalographic data were recorded. Unbeknownst to participants, reward
      outcome and frequency was random and equivalent for both rare and abundant cards;
      thus, only a perception of scarcity was true. Analysis of the
      electroencephalographic data indicated that the P300 component of the event
      related brain potential differed in amplitude for wins and losses following the
      selection of rare cards, but not following the selection of abundant cards.
      Importantly, then, we found that the perception of card rarity impacted reward
      processing even though reward feedback was independent of and subsequent to card
      selection. Our data indicate a top-down influence of the scarcity heuristic on
      reward evaluation, and specifically the processing of reward magnitude, within
      the human medial-frontal cortex. 

PMID- 27031876
TI  - Novel Uses of Video to Accelerate the Surgical Learning Curve.
AB  - Surgeons are under enormous pressure to continually improve and learn new
      surgical skills. Novel uses of surgical video in the preoperative,
      intraoperative, and postoperative setting are emerging to accelerate the learning
      curve of surgical skill and minimize harm to patients. In the preoperative
      setting, social media outlets provide a valuable platform for surgeons to
      collaborate and plan for difficult operative cases. Live streaming of video has
      allowed for intraoperative telementoring. Finally, postoperative use of video has
      provided structure for peer coaching to evaluate and improve surgical skill.
      Applying these approaches into practice is becoming easier as most of our
      surgical platforms (e.g., laparoscopic, and endoscopy) now have video recording
      technology built in and video editing software has become more user friendly.
      Future applications of video technology are being developed, including possible
      integration into accreditation and board certification. 

PMID- 27031877
TI  - Dopant-Assisted Positive Photoionization Ion Mobility Spectrometry Coupled with
      Time-Resolved Thermal Desorption for On-Site Detection of Triacetone Triperoxide
      and Hexamethylene Trioxide Diamine in Complex Matrices.
AB  - Peroxide explosives, such as triacetone triperoxide (TATP) and hexamethylene
      trioxide diamine (HMTD), were often used in the terrorist attacks due to their
      easy synthesis from readily starting materials. Therefore, an on-site detection
      method for TATP and HMTD is urgently needed. Herein, we developed a stand-alone
      dopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS)
      coupled with time-resolved thermal desorption introduction for rapid and
      sensitive detection of TATP and HMTD in complex matrices, such as white solids,
      soft drinks, and cosmetics. Acetone was chosen as the optimal dopant for better
      separation between reactant ion peaks and product ion peaks as well as higher
      sensitivity, and the limits of detection (LODs) of TATP and HMTD standard samples
      were 23.3 and 0.2 ng, respectively. Explosives on the sampling swab were
      thermally desorbed and carried into the ionization region dynamically within 10
      s, and the maximum released concentration of TATP or HMTD could be time-resolved
      from the matrix interference owing to the different volatility. Furthermore, with
      the combination of the fast response thermal desorber (within 0.8 s) and the
      quick data acquisition software to DAPP-IMS, two-dimensional data related to
      drift time (TATP: 6.98 ms, K0 = 2.05 cm(2) V(-1) s(-1); HMTD: 9.36 ms, K0 = 1.53
      cm(2) V(-1) s(-1)) and desorption time was obtained for TATP and HMTD, which is
      beneficial for their identification in complex matrices. 

PMID- 27031878
TI  - Antibiotic Resistome: Improving Detection and Quantification Accuracy for
      Comparative Metagenomics.
AB  - The unprecedented rise of life-threatening antibiotic resistance (AR), combined
      with the unparalleled advances in DNA sequencing of genomes and metagenomes, has
      pushed the need for in silico detection of the resistance potential of clinical
      and environmental metagenomic samples through the quantification of AR genes
      (i.e., genes conferring antibiotic resistance). Therefore, determining an optimal
      methodology to quantitatively and accurately assess AR genes in a given
      environment is pivotal. Here, we optimized and improved existing AR detection
      methodologies from metagenomic datasets to properly consider AR-generating
      mutations in antibiotic target genes. Through comparative metagenomic analysis of
      previously published AR gene abundance in three publicly available metagenomes,
      we illustrate how mutation-generated resistance genes are either falsely assigned
      or neglected, which alters the detection and quantitation of the antibiotic
      resistome. In addition, we inspected factors influencing the outcome of AR gene
      quantification using metagenome simulation experiments, and identified that
      genome size, AR gene length, total number of metagenomics reads and selected
      sequencing platforms had pronounced effects on the level of detected AR. In
      conclusion, our proposed improvements in the current methodologies for accurate
      AR detection and resistome assessment show reliable results when tested on real
      and simulated metagenomic datasets. 

PMID- 27031879
TI  - Non-parametric photic entrainment of Djungarian hamsters with different rhythmic
      phenotypes.
AB  - To investigate the role of non-parametric light effects in entrainment,
      Djungarian hamsters of two different circadian phenotypes were exposed to
      skeleton photoperiods, or to light pulses at different circadian times, to
      compile phase response curves (PRCs). Wild-type (WT) hamsters show daily rhythms
      of locomotor activity in accord with the ambient light/dark conditions, with
      activity onset and offset strongly coupled to light-off and light-on,
      respectively. Hamsters of the delayed activity onset (DAO) phenotype, in
      contrast, progressively delay their activity onset, whereas activity offset
      remains coupled to light-on. The present study was performed to better understand
      the underlying mechanisms of this phenomenon. Hamsters of DAO and WT phenotypes
      were kept first under standard housing conditions with a 14:10 h light-dark
      cycle, and then exposed to skeleton photoperiods (one or two 15-min light pulses
      of 100 lx at the times of the former light-dark and/or dark-light transitions).
      In a second experiment, hamsters of both phenotypes were transferred to constant
      darkness and allowed to free-run until the lengths of the active (alpha) and
      resting (rho) periods were equal (alpha:rho = 1). At this point, animals were
      then exposed to light pulses (100 lx, 15 min) at different circadian times (CTs).
      Phase and period changes were estimated separately for activity onset and offset.
      When exposed to skeleton-photoperiods with one or two light pulses, the daily
      activity patterns of DAO and WT hamsters were similar to those obtained under
      conditions of a complete 14:10 h light-dark cycle. However, in the case of giving
      only one light pulse at the time of the former light-dark transition, animals
      temporarily free-ran until activity offset coincided with the light pulse. These
      results show that photic entrainment of the circadian activity rhythm is attained
      primarily via non-parametric mechanisms, with the "morning" light pulse being the
      essential cue. In the second experiment, typical photic PRCs were obtained with
      phase delays in the first half of the subjective night, phase advances in the
      second half, and a dead zone during the subjective day. ANOVA indicated no
      significant differences between WT and DAO animals despite a significantly longer
      free-running period (tau) in DAO hamsters. Considering the phase shifts induced
      around CT0 and the different period lengths, it was possible to model the
      entrainment patterns of both phenotypes. It was shown that light-induced phase
      shifts of activity offset were sufficient to compensate for the long tau in WT
      and DAO hamsters, thus enabling a stable entrainment of their activity offsets to
      be achieved. With respect to activity onsets, phase shifts were sufficient only
      in WT animals; in DAO hamsters, activity onset showed increasing delays. The
      results of the present paper clearly demonstrate that, under laboratory
      conditions, the non-parametric component of light and dark leads to circadian
      entrainment in Djungarian hamsters. However, a stable entrainment of activity
      onset can be achieved only if the free-running period does not exceed a certain
      value. With longer tau values, hamsters reveal a DAO phenotype. Under field
      conditions, therefore, non-photic cues/zeitgebers must obviously be involved to
      enable a proper circadian entrainment. 

PMID- 27031880
TI  - Zn2+ Uptake in Streptococcus pyogenes: Characterization of adcA and lmb Null
      Mutants.
AB  - An effective regulation of metal ion homeostasis is essential for the growth of
      microorganisms in any environment and in pathogenic bacteria is strongly
      associated with their ability to invade and colonise their hosts. To gain a
      better insight into zinc acquisition in Group A Streptococcus (GAS) we
      characterized null deletion mutants of the adcA and lmb genes of Streptococcus
      pyogenes strain MGAS5005 encoding the orthologues of AdcA and AdcAII, the two
      surface lipoproteins with partly redundant roles in zinc homeostasis in
      Streptococcus pneumoniae. Null adcA and lmb mutants were analysed for their
      capability to grow in zinc-depleted conditions and were found to be more
      susceptible to zinc starvation, a phenotype that could be rescued by the addition
      of Zn2+ ions to the growth medium. Expression of AdcA, Lmb and HtpA, the
      polyhistidine triad protein encoded by the gene adjacent to lmb, during growth
      under conditions of limited zinc availability was examined by Western blot
      analysis in wild type and null mutant strains. In the wild type strain, AdcA was
      always present with little variation in expression levels between conditions of
      excess or limited zinc availability. In contrast, Lmb and HtpA were expressed at
      detectable levels only during growth in the presence of low zinc concentrations
      or in the null adcA mutant, when expression of lmb is required to compensate for
      the lack of adcA expression. In the latter case, Lmb and HtpA were overexpressed
      by several fold, thus indicating that also in GAS AdcA is a zinc-specific
      importer and, although it shares this function with Lmb, the two substrate
      binding proteins do not show fully overlapping roles in zinc homeostasis. 

PMID- 27031881
TI  - A Pilot Study of Metabolic Effects of Intravenously Given Alpha-Calcidol In
      Patients With Chronicc Renal Failure.
AB  - Disturbances of calcium homeostasis might be involved in the pathogenesis of the
      metabolic derangements associated with uraemia. Indices of glucose and
      lipoprotein metabolism as well as blood pressure were measured in nine patients
      with chronic renal failure who were on regular hemodialysis. Seven of them
      thereafter received alphacal-cidol (a synthetic analogue to active vitamin D)
      intravenously for three months. Prior to therapy the patients had, compared with
      age and sex matched controls, impaired glucose tolerance, hyperlipoproteinemia
      and raised blood pressure. Treatment with alphacalcidol reduced elevated serum
      levels of parathyroid hormone (PTH). Concomitantly there was a reduction of
      fasting blood glucose and HbA1C (glycosylated hemoglobin) concentrations and an
      improvement of the glucose tolerance, whereas insulin concentrations were
      unaffected. There was a reduction of whole serum triglycerides and an increase of
      HDL cholesterol. A significant decrease was also observed for systolic blood
      pressure. This pilot study suggests that treatment with active vitamin D,
      probably through its effects on calcium metabolism, is beneficial with regard to
      the metabolic disturbances in uraemia. 

PMID- 27031882
TI  - Mucinous Adenocarcinoma of the Prostate Presenting as a Retrovesical Cyst.
AB  - A 63-year-old man presented with acute urinary retention due to a retrovesical
      cystic tumor. Investigation revealed mucinous prostatic adenocarcinoma with
      metastatic involvement of testis and epididymis. He was treated with retrovesical
      tube drainage, bilateral orchiectomy and epididymectomy and cyproterone acetate. 

PMID- 27031883
TI  - An empirical Kaiser criterion.
AB  - In exploratory factor analysis (EFA), most popular methods for dimensionality
      assessment such as the screeplot, the Kaiser criterion, or-the current gold
      standard-parallel analysis, are based on eigenvalues of the correlation matrix.
      To further understanding and development of factor retention methods, results on
      population and sample eigenvalue distributions are introduced based on random
      matrix theory and Monte Carlo simulations. These results are used to develop a
      new factor retention method, the Empirical Kaiser Criterion. The performance of
      the Empirical Kaiser Criterion and parallel analysis is examined in typical
      research settings, with multiple scales that are desired to be relatively short,
      but still reliable. Theoretical and simulation results illustrate that the new
      Empirical Kaiser Criterion performs as well as parallel analysis in typical
      research settings with uncorrelated scales, but much better when scales are both
      correlated and short. We conclude that the Empirical Kaiser Criterion is a
      powerful and promising factor retention method, because it is based on
      distribution theory of eigenvalues, shows good performance, is easily visualized
      and computed, and is useful for power analysis and sample size planning for EFA.
      (PsycINFO Database Record

PMID- 27031884
TI  - A National Perspective of the Risk, Presentation, and Outcomes of Pediatric
      Thyroid Cancer.
AB  - IMPORTANCE: Thyroid cancer is the most common endocrine malignant neoplasm in
      children and adolescents. Despite a more advanced presentation of thyroid cancer,
      younger patients tend to have a more favorable prognosis and a lower mortality
      rate than adults with thyroid cancer. OBJECTIVE: To examine the presentation and
      outcomes of thyroid cancer in pediatric patients. DESIGN, SETTING, AND
      PARTICIPANTS: A cross-sectional weighted analysis was performed using data from
      the Nationwide Inpatient Sample from January 1, 2003, to December 31, 2010.
      Patient data were derived from a sample of 20% of community hospitals in the
      United States. Six hundred forty-four children and adolescents (age, <18 years;
      hereinafter referred to as children) with thyroid cancer were compared with 43
      536 adults (age, >=18 years) with thyroid cancer. Data were analyzed from
      December 7, 2014, to November 19, 2015. EXPOSURES: Thyroid cancer and
      thyroidectomy. MAIN OUTCOMES AND MEASURES: Presentation and management
      characteristics of thyroid cancer and thyroidectomy outcomes in relation to
      surgeon volume and specialty. RESULTS: A total of 644 cases of pediatric thyroid
      cancer were included (female, 77.3%; mean [SEM] age, 13.8 [0.2] years),
      corresponding to a weighted sample of 32 563. Compared with adults with thyroid
      cancer, children were more likely to present with cervical lymph node involvement
      (31.5% vs 14.7%; odds ratio [OR], 2.29; 95% CI, 1.76-2.97; P < .001) and lung
      metastases (5.7% vs 2.2%; OR, 2.79; 95% CI, 1.82-4.28; P < .001), whereas bone
      metastases were more frequent in adults (0.3% vs 1.1%; OR, 0.23; 95% CI, 0.06
      0.90; P = .04). Children were more likely to be treated by a low-volume surgeon
      (26.9% vs 16.0%; OR, 2.09; 95% CI, 1.26-3.48; P = .005) or a pediatric surgeon
      (14.5% vs 9.6%; OR, 1.66; 95% CI, 1.04-2.67; P = .04) and in a low-volume
      hospital (20.5% vs 15.2%; OR, 2.97; 95% CI, 1.60-5.54; P < .001) or a teaching
      hospital (81.7% vs 63.1%; OR, 3.61; 95% CI, 2.33-5.60; P < .001). Compared with
      those treated by low-volume surgeons, children treated by high-volume surgeons
      were less likely to experience postoperative complications (14.3% vs 35.9%; OR,
      0.16; 95% CI, 0.05-0.51; P = .002) or a hospital stay of more than 1 day (49.8%
      vs 67.9%; OR, 0.36; 95% CI, 0.15-0.90; P = .03). Management by pediatric surgeons
      did not significantly alter the risk for postoperative complications compared
      with other specialties (21.3% vs 18.5%; OR, 1.71; 95% CI, 0.64-4.53, P = .28).
      Management of thyroid cancer in children was significantly more costly (>$10
      067.08/case) compared with adults (P = .04). CONCLUSIONS AND RELEVANCE: Compared
      with thyroid cancer in adults, pediatric thyroid cancer is more likely to present
      as advanced disease and to be managed by low-volume or pediatric surgeons. In
      addition, within the United States, surgeon volume appears to be more crucial in
      determining thyroidectomy outcomes than the surgeon's field of specialization.

PMID- 27031885
TI  - Nonradiative Energy Transfer from Individual CdSe/ZnS Quantum Dots to Single
      Layer and Few-Layer Tin Disulfide.
AB  - The combination of zero-dimensional (0D) colloidal CdSe/ZnS quantum dots with tin
      disulfide (SnS2), a two-dimensional (2D)-layered metal dichalcogenide, results in
      0D-2D hybrids with enhanced light absorption properties. These 0D-2D hybrids,
      when exposed to light, exhibit intrahybrid nonradiative energy transfer from
      photoexcited CdSe/ZnS quantum dots to SnS2. Using single nanocrystal
      spectroscopy, we find that the rate for energy transfer in 0D-2D hybrids
      increases with added number of SnS2 layers, a positive manifestation toward the
      potential functionality of such 2D-based hybrids in applications such as
      photovoltaics and photon sensing.

PMID- 27031887
TI  - Improving Prostate Cancer Screening and Diagnosis: Health Policy and Biomarkers
      Beyond PSA.

PMID- 27031886
TI  - A Meta-Analysis to Determine if Lower Extremity Muscle Strengthening Should Be
      Included in Military Knee Overuse Injury-Prevention Programs.
AB  - CONTEXT:  Knee overuse injuries are the most common musculoskeletal complaints in
      military trainees and are common in active-duty warfighters. Muscle strengthening
      is usually recommended; however, research is conflicting in this area, which
      makes it difficult to develop effective screening, prevention, and training
      interventions for warfighters. OBJECTIVE:  To determine if lower extremity
      muscular weakness contributes to knee overuse injuries and identify specific
      muscular involvement. DATA SOURCES:  We searched MEDLINE, PubMed, Web of Science,
      SPORTDiscus, CINAHL, and Military & Government Collection and reference lists of
      relevant articles published between January 1, 2000, and January 1, 2013. STUDY
      SELECTION:  For inclusion, requirements were uninjured and injured groups;
      provision of the sample size, means, and standard deviations for all groups;
      identification of the specific muscles assessed; and clearly defined knee injury.
      DATA EXTRACTION:  Sample size, sex, and muscle strength means and standard
      deviations. DATA SYNTHESIS:  Twenty-five studies met these criteria. We used the
      Scottish Intercollegiate Guidelines Network algorithm to determine the
      appropriate tool for appraising article quality. Unweighted random-effects model
      meta-analyses were conducted. Separate meta-analyses were performed for the
      moderators of strength measurement scale (absolute or normalized muscle
      strength), muscle group, and sex. A weighted random-effects model with a Hedges g
      effect metric and 95% confidence intervals were used for comparison across
      studies. CONCLUSIONS:  Our meta-analysis suggests that individuals with symptoms
      of a knee overuse injury have lower absolute and normalized hip muscle strength.
      Specifically, they had lower absolute hip external-rotator, knee-extensor, and
      knee-flexor strength, as well as lower normalized hip external-rotator, hip
      extensor, and hip-abductor strength, compared with asymptomatic control
      participants. The findings suggest a possible link between lower hip and thigh
      strength and knee overuse injuries. Further research is needed to determine if
      weakness is a cause or a result of knee overuse injuries before screening and
      intervention can be developed for at-risk warfighters.

PMID- 27031889
TI  - Thermodynamic Stability of Low- and High-Index Spinel LiMn2O4 Surface
      Terminations.
AB  - Density functional theory calculations are performed within the generalized
      gradient approximation (GGA+U) to determine stable terminations of both low- and
      high-index spinel LiMn2O4 (LMO) surfaces. A grand canonical thermodynamic
      approach is employed, permitting a direct comparison of off-stoichiometric
      surfaces with previously reported stoichiometric surface terminations at various
      environmental conditions. Within this formalism, we have identified trends in the
      structure of the low-index surfaces as a function of the Li and O chemical
      potentials. The results suggest that, under a range of chemical potentials for
      which bulk LMO is stable, Li/O and Li-rich (111) surface terminations are
      favored, neither of which adopts an inverse spinel structure in the subsurface
      region. This thermodynamic analysis is extended to identify stable structures for
      certain high-index surfaces, including (311), (331), (511), and (531), which
      constitute simple models for steps or defects that may be present on real LMO
      particles. The low- and high-index results are combined to determine the relative
      stability of each surface facet under a range of environmental conditions. The
      relative surface energies are further employed to predict LMO particle shapes
      through a Wulff construction approach, which suggests that LMO particles will
      adopt either an octahedron or a truncated octahedron shape at conditions in which
      LMO is thermodynamically stable. These results are in agreement with the
      experimental observations of LMO particle shapes.

PMID- 27031890
TI  - Intrathecal or intraventricular colistin: a review.
AB  - Central Nervous System (CNS) infections related to external ventricular
      derivation are a major complication of patients undergoing neurosurgical
      procedures. Antimicrobial treatment of CNS infections should be based not only on
      the susceptibility of the isolated microorganism, but also on the treatment's
      pharmacokinetic properties demonstrating the passage of the molecule through the
      blood-brain barrier. When CNS infections are caused by multi-drug resistant Gram
      negative bacteria, intrathecal colistin is considered an effective and safe
      option. We review the literature of intrathecal/intraventricular use of colistin,
      comprehensive of both pharmacokinetic data and clinical experiences.

PMID- 27031891
TI  - Detection of HPV and co-infecting pathogens in healthy Italian women by multiplex
      real-time PCR.
AB  - Several pathogens can be transmitted sexually and are an important cause of
      morbidity among sexually active women. The aim of the study was to detect the
      presence of human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria
      gonorrhoeae (NG), Trichomonas vaginalis (TV), Mycoplasma hominis (MH), Mycoplasma
      genitalium (MG), Ureaplasma urealyticum (UU), and Ureaplasma parvum (UP) in a
      group of 309 healthy women enrolled at the San Camillo - Forlanini hospital of
      Rome by using two multiplex real-time PCR assays based on TOCE(r) technology. The
      women's ages ranged from 34 to 60 years, median 49 [IQR 45-54]. Of the 309 women
      tested, HPV DNA was detected in 77/309 (24.9%) patients. Of these, 44 (14.2%)
      harboured a single infection while 33 (10.7%) were infected by multiple
      genotypes. Prevalence of HPV infection was highest among females aged 40-50 years
      (15.2%). Of the other pathogens sought, CT, MG and NG were not detected while
      positive results were found for MH (12/309, 3.9%), TV (4/309, 1.3%), UP (89/309,
      28.8%) and UU (14/309, 4.5%). Co-infections were as follows: 5 MH/HPV, 4 TV/HPV,
      34 UP/HPV and 9 UU/HPV. In HPV-positive women, the probability of being infected
      by UP and UU was 2.5 (p=0.00045) and 6 fold higher (p=0.0016) than in HPV
      negative women. The study supports the use of multiplex real-time PCR assays in a
      routine diagnostic setting. The high sensitivity and specificity of these assays
      along with the simultaneous detection of the most common sexually transmitted
      pathogens confers an advantage with respect to more obsolete methods reducing
      costs and time to diagnosis.

PMID- 27031892
TI  - Anti-infectives for systemic use prescribed in a Spanish hospital between 2009
      2013.
AB  - The overuse and misuse of antimicrobials contribute to the emergence of
      antibiotic-resistant bacteria. The aim of this work was to analyse all the anti
      infectives for systemic use (J ATC group) prescribed at the University Clinic
      Hospital of Valladolid (Spain) for the years 2009-2013. Amounts of anti
      infectives (antibacterials, antifungals and antivirals) used in the period 2009
      2013 were expressed as defined daily doses (DDDs) and as total expenditure, and
      the significance of the difference in consumption of anti-infectives and the
      relevant expenditure between years was evaluated from the overlapping of the
      corresponding confidence intervals at 95% confidence level of DDDs and
      expenditure. The results obtained showed that DDDs and expenditure of
      antibacterials decreased in the period 2009-2013. Antimycotics showed an upward
      trend in expenditure and DDDs in the five-year study period, but with major
      oscillations. The consumption of antivirals was practically constant in the
      period 2009-2011; in 2012, a significant reduction was observed and this
      reduction was conserved in 2013, although their expenditure increased year by
      year. In conclusion, in the period 2009-2013, expenditure on anti-infectives
      increased year to year. However, this increase in expenditure resulted in a
      downward trend of DDDs.

PMID- 27031893
TI  - Characterisation of drug resistance of nosocomial ESBL-producing E. coli isolates
      obtained from a Turkish university hospital between 2009 and 2012 by pulsed field
      gel electrophoresis and antibiotic resistance tests.
AB  - In this study, drug resistance of 28 ESBL-producing Escherichia coli isolates
      obtained from 144 patients hospitalized at the Yuzuncuyil University Hospital at
      Van (YUH), Turkey, between 2009 and 2012 were characterized by pulsed field gel
      electrophoresis and antibiotic susceptibility tests. Antibiotic resistance
      profile was determined by Phoenix automated system (BD, USA). The ratio of ESBL
      producing E. coli strains was determined to be 19.4% (28 out of 144 E. coli
      isolates). It was determined that the anaesthesiology, paediatrics and thoracic
      medicine intensive care units in YUH were cross-contaminated between 2009 and
      2012 by ESBL-producing E. coli strains, which is a sign of nosocomial infection
      in YUH. Analysis of PFGE results gave rise to two main PFGE profiles, profile-A
      with four subprofiles and profile-B with three subprofiles, where profile-A
      predominates over profile-B (14%). Comparison of the antibiotic resistance
      profile with the PFGE profile yielded similarities while some differences also
      exist due to either identical restriction enzyme cutting sites with slightly
      different genetic sequences in between the cutting sites or newly formed
      restriction enzyme cutting sites that do not affect antibiotic resistance genes.
      Enterobacteriaceae, particularly E. coli, have developed resistance in YUH by
      producing ESBLs against oxyimino and non-oxyimino cephalosporins, and penicillin
      type antibiotics. Therefore, more effective antibiotics such as cefoxitin or
      cefoperazone-sulbactam should be used for the treatment of future nosocomial
      infections in YUH while hospital staff should take care with hygiene, such as
      hand washing.

PMID- 27031894
TI  - Hypertransaminasaemia in children with viral gastroenteritis.
AB  - We investigated the rates of increase in serum aspartate aminotransferase (AST)
      and alanine aminotransferase (ALT) levels of patients with rotavirus, norovirus
      and enteric adenovirus gastroenteritis. Two hundred children with viral
      gastroenteritis were evaluated for hypertransaminasaemia retrospectively. The
      patients were between 0 - 17 years (mean +/- SD: 5.10 +/- 3.01) of age. ALT was
      elevated up to 67 IU/L in 7 (8.5%) patients in the rotavirus group (n=82),
      whereas it was elevated in 3 (4.0%) and 1 (2.3%) patients in the norovirus (n=74)
      and adenovirus (n=44) groups, respectively. AST was elevated up to 89 IU/L in 20
      (24.4%) patients in the rotavirus group, whereas it was elevated in 6 (8.1%) and
      1 (2.3%) patients in the norovirus and adenovirus groups, respectively. Both
      transaminases were elevated in 7.3%, 1.4%, and 2.3% of patients in the rotavirus,
      norovirus, and adenovirus groups, respectively. The increases in ALT and AST
      levels were found to be significantly higher in the rotavirus group (n=27) than
      in the norovirus (n=9), and adenovirus group (n=2) (p<0.05). Mean serum ALT and
      AST levels in the rotavirus group were significantly higher than those in the
      norovirus and adenovirus group (p<0.05). Our study investigated the correlation
      between viral gastroenteritis and hypertransaminasaemia. When evaluating a
      patient with hypertransaminasaemia physicians should remember to consider acute
      gastroenteritis due to some viruses as a cause of elevated AST and ALT.

PMID- 27031895
TI  - The role of overweight and obesity in urinary tract infection in children.
AB  - This study was conducted to determine the relationship between overweight/obesity
      and UTI in children. A comparison was made, in terms of overweight and obesity,
      between 135 children with UTI (case group) and 135 healthy children (control
      group). UTI was diagnosed through urine culture. Dimercaptosuccinic acid renal
      scanning (DMSA) was also used to distinguish between lower UTI and acute
      pyelonephritis. Overweight and obesity were determined based on standard body
      mass index (BMI) curves. There were 12 (8.8%) overweight and 26 (19.2%) obese
      children in the case group. Four (3.0%) overweight and five (3.7%) obese children
      were found in the control group. There was a significant difference between the
      two groups regarding overweight and obesity frequencies. However, no such
      difference existed between children with cystitis and acute pyelonephritis. This
      study showed a significant relationship between overweight/obesity and UTI.
      Therefore, overweight and obesity may play a role in the pathogenesis of UTI in
      children.

PMID- 27031896
TI  - Serological survey of Echinococcus granulosus in nomads of southwest Iran using
      the ELISA method during 2014-15.
AB  - Echinococcosis is one of the diseases common to humans and animals worldwide and
      its metacestode form Echinococcus granulosus is the cause of disease. Diagnosis
      based on clinical symptoms is a problem. However, using serological methods such
      as ELISA, specific antibodies can be determined. Based on the medical and
      economic importance of the disease, this study aimed to undertake a serological
      survey of human echinococcosis in Behbahan nomads using the ELISA method during
      2014-15. In a descriptive study, 180 blood samples were collected and analysed
      from the tribes in the four geographic regions of Behbahan city. The obtained
      sera were assessed for the presence of IgG antibodies against hydatid cyst.
      Demographic data were collected using a questionnaire and the results were
      analysed by SPSS software. In all, 175 persons (97.2%) tested negative while five
      (2.8%) were positive. The most frequent was in people over 50 years with three
      persons (1.7%). In the 40-50 years age group, two subjects (1.1%) tested
      positive. 62 (34.4%) of the subjects were female and 118 (65.6%) were male, among
      which four men (2.2%) and one woman (0.6%) were infected. Overall, the most
      infected were men. Of the infected persons, three lived in the East, one in the
      South and one in the West of the city. All subjects had a history of contact with
      dogs. According to the results of this study, the prevalence was high in the area
      and therefore disease control programmes are recommended.

PMID- 27031897
TI  - The investigation of oxacillinase/metallo-beta-lactamase genes and clonal
      analysis in carbapenem-resistant Klebsiella pneumoniae.
AB  - Infections due to carbapenem-resistant Klebsiella pneumoniae represent a growing
      problem nationally. In our study, we aimed to examine carbapenem-resistant K.
      pneumoniae with multiple resistance isolated in the intensive care unit of our
      hospital. Isolates were investigated for the presence of oxacillinase and metallo
      beta lactamase genes with a view to determining the clonal relationship between
      the strains intensely over a short period. Strain identification was completed
      with conventional methods and automated identification kit. OXA-58, OXA-23, OXA
      51, OXA-24 and OXA-48 and metallo-beta lactamase genes IPM, VIM, SPM, SIM, GIM
      and NDM-1 were investigated with PCR. For clonal relationships of carbapenem
      resistant strains, the PFGE experiment was performed. While all of these
      carbapenem-resistant strains were positive for OXA-48, the resistant genes NDM-1,
      VIM, KPC, IPM, SPM, GIM, SIM, OXA-23, OXA-24, OXA-58 and OXA-51 were not
      observed. When molecular typing results were investigated, PFGE determined clonal
      distribution of three pulsotypes. However, it was observed that the strains
      intensified in a single clone and this was assessed as the outbreak isolate. The
      results of this study showed the primary enzyme responsible for carbapenem
      resistance in K. pneumoniae strains in our hospital is still OXA-48. To prevent
      the spread of carbapenem-resistant K. pneumoniae isolates, with epidemic
      potential, national-level monitoring and effective infection control precautions
      should be enforced.

PMID- 27031898
TI  - Metastatic muscle abscesses complicating infected total hip arthroplasty.
AB  - A 73-year-old woman with rheumatoid arthritis presented to our institution with
      infection of her right total hip arthroplasty. On admission, a draining sinus
      tract over the hip and a palpable mass in the left lower posterior region of the
      neck were detected. The contrast CT scan showed a large abscess in the trapezius
      muscle and multiple abscesses involving muscle of the neck and right shoulder.
      Intraoperative specimens from the muscle abscess were positive for presumably the
      same methicillin-resistant Staphylococcus aureus that sustained the prosthetic
      joint infection. Prolonged intravenous daptomycin led to remission of the muscle
      abscess and control of the prosthetic joint infection. The patient refused
      revision total hip arthroplasty and oral cotrimoxazole was prescribed for chronic
      suppression of the infection. Three years after the primary surgery there was
      stable remission of the prosthetic joint infection. This rare case demonstrates
      the severity of prosthetic joint infections sustained by multiresistant bacteria
      in immunocompromised hosts, which may result in their bacteraemic spread.

PMID- 27031899
TI  - Bloodstream infection with Oligella ureolytica: a case report and review of the
      literature.
AB  - Oligella ureolytica is an emerging bacteria rarely implicated as a human
      pathogen. It is mostly recovered from urinary and respiratory tract specimens as
      a commensal organism, but very seldom from bloodstream infections. It is rarely
      reported in the literature, probably due to misidentification of the organism or
      uncertainty of its pathogenicity.

PMID- 27031900
TI  - A life-threatening brainstem compression by cerebral Echinococcus granulosus.
AB  - Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus
      granulosus. It is of worldwide importance, and is widespread in the Mediterranean
      region and Middle East. This tapeworm shows great intraspecific variation in
      relation to host specificity, epidemiology and morphology. This variability led
      in previous years to the identification of ten (G1-G10) different genotypes of
      the parasite. Cerebral localization of E. granulosus is not common: it especially
      affects children and is more frequently located in the supratentorial region. It
      can be life-threatening due to its localization in eloquent areas especially in
      the posterior fossa. Despite the benign nature of hydatid cyst, invasion of
      critical areas may cause significant mortality and morbidity in some patients.
      Urgent surgical decompression and adjuvant medical treatment must be employed as
      soon as possible in these patients. We present a clinical case of life
      threatening brainstem compression in a child due to a rare form of CE which was
      confirmed with biomolecular techniques. She presented with respiratory distress
      and progressive quadriparesis. All cysts were removed by microsurgical technique
      and albendazole was given postoperatively for one year with regular follow-ups.

PMID- 27031901
TI  - An unnoticed origin of fever: periapical tooth abscess. Three case reports and
      literature review.
AB  - Dental infections may lead to severe local or systemic infections such as
      endocarditis, brain abscesses and mediastinitis. Fever may be the only symptom.
      We aim to highlight dental/odontogenic abscesses as the occult source of
      unexplained fever by reporting on three cases and reviewing the relevant
      literature. Early dental evaluation and referral of patients with persistent
      fever (even without any oral symptoms) to a dentist plays a critical role in
      preventing unnecessary, time-consuming and high-cost further diagnostic tests and
      invasive procedures. A simple panoramic dental radiography may suffice to
      establish the diagnosis.

PMID- 27031902
TI  - Report of an immunocompetent case with disseminated infection due to Nocardia
      otitidiscaviarum: Identification by 16S rRNA gene sequencing.
AB  - Nocardia otitidiscaviarum belongs to the agents of opportunistic infections seen
      in immunocompromised patients, but may occur rarely in immunocompetent patients.
      In this report we described a case of a previously healthy 69-year-old woman with
      cerebral and retroperitoneal abscess due to Nocardia otitidiscaviarum. The
      patient was admitted to hospital because of loss of strength in her right arm and
      leg. Nocardia spp. was isolated from the abscess material. The intracranial
      lesions were drained by stereotactic craniotomy. The large abscess located around
      the left kidney was drained and microscopic examination of aspirated material
      showed Nocardia spp. For species identification, 16S rRNA gene sequencing was
      carried out and was 100% concordant with Nocardia otitidiscaviarum. Use of 16S
      rDNA gene sequencing for identification permits detection of rare aetiologic
      agents that cause brain abscesses.

PMID- 27031903
TI  - Historical perspective of brucellosis: a microbiological and epidemiological
      overview.
AB  - The historical process of brucellosis extends back to humankind's first contact
      with animals. Although brucellosis is a sporadic disease observed in animals in
      certain regions of the world, it is an important disease in humans that can
      affect many organs and systems due to the consumption of contaminated milk or
      milk products. Studies have shown that the presence of Brucella dates back to 60
      million years ago. In 450 BC, Hippocrates described a disease similar to
      brucellosis. Since Hippocrates' time, brucellosis has been characterized by
      fever. Our aim is to investigate selfless work undertaken by scientists on the
      epidemiology, diagnosis and clinical findings of brucellosis until today, and to
      gain a historical perspective about the disease that is as old as human history,
      still has importance today, causes economic losses in treated animals and harms
      human health.

PMID- 27031904
TI  - Discrepancy between immunosuppressive status and extensiveness of fungal
      infections?

PMID- 27031905
TI  - Erratum: A probable drug-to-drug interaction between voriconazole and haloperidol
      in a slow metabolizer of CYP2C19 patient.

PMID- 27031906
TI  - Erratum: Evaluation of CHROMagar Candida, VITEK2 YST and VITEK(r) MS for
      identification of Candida strains isolated from blood cultures.

PMID- 27031907
TI  - Co@Co3 O4 @PPD Core@bishell Nanoparticle-Based Composite as an Efficient
      Electrocatalyst for Oxygen Reduction Reaction.
AB  - Durable electrocatalysts with high catalytic activity toward oxygen reduction
      reaction (ORR) are crucial to high-performance primary zinc-air batteries (ZnABs)
      and direct methanol fuel cells (DMFCs). An efficient composite electrocatalyst,
      Co@Co3 O4 core@shell nanoparticles (NPs) embedded in pyrolyzed polydopamine (PPD)
      is reported, i.e., in Co@Co3 O4 @PPD core@bishell structure, obtained via a three
      step sequential process involving hydrothermal synthesis, high temperature
      calcination under nitrogen atmosphere, and gentle heating in air. With Co@Co3 O4
      NPs encapsulated by ultrathin highly graphitized N-doped carbon, the catalyst
      exhibits excellent stability in aqueous alkaline solution over extended period
      and good tolerance to methanol crossover effect. The integration of N-doped
      graphitic carbon outer shell and ultrathin nanocrystalline Co3 O4 inner shell
      enable high ORR activity of the core@bishell NPs, as evidenced by ZnABs using
      catalyst of Co@Co3 O4 @PPD in air-cathode which delivers a stable voltage profile
      over 40 h at a discharge current density of as high as 20 mA cm(-2) .

PMID- 27031908
TI  - Nutrition and Frailty.

PMID- 27031909
TI  - Nutrition, Frailty and Disabilities.

PMID- 27031910
TI  - Prevalence and Types of Anemia and Associations with Functional Decline in
      Geriatric Inpatients.
AB  - BACKGROUND: The prevalence of anemia in hospitalized seniors has been linked to
      poor functional outcomes, increased mortality, and longer hospital stays, and has
      been associated with advancing age, male sex, and cognitive impairment. Despite
      the potential for complications, anemia often is undiagnosed and/or untreated in
      seniors. OBJECTIVES: Examine (a) the distribution of anemia diagnosis and
      treatment in patients in a rehabilitation hospital, and (b) patients' cognitive
      and functional outcomes. DESIGN: Retrospective chart review of medical records of
      132 patients. MEASUREMENTS: The presence and type of anemia were determined based
      on the World Health Organization criteria for adults and Smith's algorithm,
      respectively. The Mini-Mental State Exam (MMSE) was used to measure cognitive
      status. Functional impairment was assessed using the Functional Independence
      Measure (FIM). RESULTS: The mean age of the sample was 82.20 years, with 68%
      being female, the mean MMSE and FIM scores were 23.95 (SD = 4.3) and 82.82 (SD =
      15.63), respectively. In total, 67% of males and 46% of females were anemic (P <
      0.05). The majority of anemias were caused by nutritional deficiencies. The
      percent of anemic females receiving treatment for anemia was higher (71%) than
      the percent of anemic males (46%) (P < 0.05). The majority of the patients
      improved functionally regardless of anemia status. CONCLUSIONS: Results indicated
      that a substantial number of patients in a geriatric hospital were anemic, with
      significant percentage going untreated. The overall improvement in patients'
      functional abilities suggests that remedial rehabilitation of frail seniors has
      an impact on recovery during their hospital stay.

PMID- 27031911
TI  - Nutrition, Frailty and Prevention of Disabilities with Aging.
AB  - The heterogeneous group of older adults may be differentiated into three
      subgroups in order to facilitate the development and implementation of
      personalized healthcare interventions: 1) "disabled individuals" (i.e., those
      needing assistance in the accomplishment of basic activities of daily living), 2)
      "frail individuals" (i.e., those presenting some limitations and impairments in
      the absence of functional disability), and 3) the "robust individuals" (i.e.,
      those who are neither frail or disabled). Despite the growing evidence linking
      frailty to poor outcomes, this syndrome is yet adequately considered in the
      clinical practice. There is indeed a lack of recognition of frail individuals,
      frequently leading to inadequate or inappropriate offer of healthcare services.
      The assessment of frailty in older adults is recommended to preventively act
      before the activation of the irreversible cascade of disability. Characteristic
      features of frailty (e.g., weakness, low energy, slow walking speed, low physical
      activity, and weight loss) clearly suggest the existence of a close link between
      nutrition and the status of extreme vulnerability (to intend both from a physical
      and cognitive viewpoint). Interestingly, recent clinical experiences in the field
      of frailty and nutrition have demonstrated that this syndrome is often related to
      relevant prevalence of malnutrition and risk of becoming malnourished. In the
      present article, it is proposed a review of existing evidence in the field of
      nutrition and frailty. Potential nutritional interventions for preventing frailty
      and age-related disabling conditions are also discussed. 

PMID- 27031912
TI  - Combined Increases in Muscle-Strengthening Activity Frequency and Protein Intake
      Reveal Graded Relationship with Fat-Free Mass Percentage in U.S. Adults, NHANES
      (1999-2004).
AB  - BACKGROUND: Age-related loss of muscle mass and related ailments are of concern
      due to associations with disabilities and morbidity as well as constituting a
      substantial healthcare burden. Muscle-strengthening activities and adequate
      protein ingestion are recommended for all-age adults in an effort to stave off
      age-related muscle atrophy. Muscle building abilities decline with age but most
      research focuses on muscle wasting in the elderly. OBJECTIVES: To examine the
      independent and combined associations of protein intake (g?kg-1?day-1) and muscle
      strengthening frequency (times?week-1, MSF) on fat-free mass percentage (FFM%).
      DESIGN SETTING AND PARTICIPANTS: This cross-sectional analysis of a population
      based sample with data from the non-institutionalized persons in the United
      States participating in the National Health and Nutrition Examination Survey
      (cycles 1999-2000, 2001-2002, 2003-2004) consisted of male (n=2,499) and female
      (n=2,373) participants 20-49 years of age for analyses. MEASUREMENTS: MSF was
      determined by self-report and protein intake was calculated from a 24-hour
      recall. Differences in FFM% from bioelectrical impedance analysis was estimated
      using multiple linear regression models controlling for education, race
      ethnicity, standing height, and total Caloric intake. RESULTS: One unit increase
      in MSF or protein intake (beta-coefficient, +/-E) was associated with
      significantly more FFM% in males (0.6+/-0.1%; 3.5+/-0.4%) and females (0.4+/
      0.1%; 5.9+/-0.4%). Independent of protein intake, males and females with MSF=0
      had mean +/-SE FFM% of 74.4+/-0.4 and 60.7+/-0.3, respectively, while mean +/-SE
      FFM% of males and females who met the recommendation of >=2 times per week were
      77.9+/-0.5 and 63.0+/-0.4. Independent of MSF, males and females with protein
      intakes below the recommended dietary allowance (RDA) of 0.8 g?kg-1?day-1 had
      mean +/-SE FFM% of 74.0+/-0.6 and 58.2+/-0.6, respectively, while mean +/-SE FFM%
      of those whose intakes exceeded the recommendation were 75.6+/-0.4 and 62.0+/
      0.4. The subgroup with the highest mean +/-SE FFM% (80.9 +/-0.73) comprised males
      with MSF >=2 times per week who also consumed >1.4 g?kg-1?day-1. CONCLUSION: The
      MSF-protein intake dose relationship with FFM% suggests that performing muscle
      strengthening activities >2 times per week while consuming protein above the RDA
      may result in more fat-free mass and slow age-related losses of muscle mass.

PMID- 27031913
TI  - Determining the Cut-off Values for Sarcopenia in the Korean Elderly Population
      Using Bioimpedance Analysis.
AB  - BACKGROUND: Bioimpedance analysis (BIA) is known to be a useful method for
      assessing sarcopenia because cost-effective and not involving radiation exposure.
      However, the cut-off values for sarcopenia using BIA have not yet been determined
      in the Korean population. OBJECTIVES: To establish the cut-off values for
      sarcopenia in the Korean elderly population with the use of BIA. METHODS: Body
      composition assessed by BIA was obtained in 7,641 participants aged 20-34 years
      and 3,902 participants aged >=65 years from data routinely collected during
      health examinations at Seoul National University Gangnam Center. Appendicular
      skeletal muscle mass was adjusted for height and weight. Gender-specific cut
      points for class I and class II sarcopenia were defined as 1 and 2 standard
      deviations below the mean in the reference group aged 20-34 years, respectively.
      In addition, the gender-specific, lowest 20th percentile cut-offs for muscle mass
      in participants aged >=65 years were determined. RESULTS: The cut-offs for class
      I and class II sarcopenia in men for height-adjusted appendicular skeletal mass
      were 6.74 kg/m2 and 5.96 kg/m2 and for weight-adjusted appendicular skeletal mass
      were 29.4% and 27.4%, respectively; those in women for height-adjusted
      appendicular skeletal mass were 4.93 kg/m2 and 4.35 kg/m2, and for weight
      adjusted appendicular skeletal mass were 25.6% and 23.9%, respectively. The
      lowest 20th percentile cut-offs for height-adjusted and weight-adjusted
      appendicular skeletal mass were 6.69 kg/m2 and 28.9% in men, and 5.76 kg/m2 and
      24.5% in women, respectively. Based on the derived cut-offs, prevalence of class
      II sarcopenia in participants >=65 years of age for height-adjusted and weight
      adjusted appendicular skeletal mass was 3.7% and 3.5% in men, and 0.2% and 11.2%
      in women, respectively. Among the above-mentioned definitions, sarcopenia by
      height-adjusted appendicular skeletal mass was significantly associated with 2
      year mortality in older participants. CONCLUSIONS: Muscle mass deficit in the
      Korean population can be assessed based on the cut-offs determined in this study
      using BIA.

PMID- 27031914
TI  - Is It Fe(III)-Oxyl Radical That Abstracts Hydrogen in the C-H Activation of TauD?
      A Theoretical Study Based on the DFT Potential Energy Surfaces.
AB  - Taurine:alpha-ketoglutarate dioxygenase (TauD) is one of the most important
      enzymes in the alpha-ketoglutarate dioxygenase family, which are involved in many
      important biochemical processes. TauD converts taurine into amino acetaldehyde
      and sulfite at its nonheme iron center, and a large H/D kinetic isotope effect
      (KIE) has been found in the hydrogen atom transfer (HAT) of taurine suggesting a
      large tunneling effect. Recently, highly electrophilic Fe(III)-oxyl radicals have
      been proposed as a key species for HAT in the catalytic mechanism of C-H
      activation, which might be prepared prior to the actual HAT. In order to
      investigate this hypothesis and large tunneling effect, DFT potential energy
      surfaces along the intrinsic reaction path were generated. The predicted rate
      constants and H/D KIEs using variational transition-state theory including
      multidimensional tunneling, based on these potential surfaces, have excellent
      agreement with experimental data. This study revealed that the reactive processes
      of C-H activation consisted of two distinguishable parts: (1) the substrate
      approaching the Fe(IV)-oxo center without C-H bond cleavage, which triggers the
      catalytic process by inducing metal-to-ligand charge transfer to form the Fe(III)
      oxyl species, and (2) the actual HAT from the substrate to the Fe(III)-oxyl
      species. Most of the activation energy was used in the first part, and the actual
      HAT required only a small amount of energy to overcome the TS with a very large
      tunneling effect. The donor-acceptor interaction between sigmaC-H and sigma*Fe-O
      orbitals reduced the activation energy significantly to make C-H activation
      feasible.

PMID- 27031915
TI  - Special Focus Issue: Transdermal, Topical and Folicular Drug Delivery Systems.

PMID- 27031916
TI  - Intradermal and follicular delivery of adapalene liposomes.
AB  - BACKGROUND: Adapalene is a widely used topical anti-acne drug; however, it has
      many side effects. Liposomal drug delivery can play a major role by targeting
      delivery to pilosebaceous units, reducing side effects and offering better
      patient compliance. OBJECTIVE: To prepare and evaluate adapalene-encapsulated
      liposomes for their physiochemical and skin permeation properties. METHODS: A
      liposomal formulation of adapalene was prepared by the film hydration method and
      characterized for shape, size, polydispersity index (PDI), encapsulation
      efficiency and thermal behavior by techniques such as Zetasizer(r), differential
      scanning calorimetry and transmission electron microscopy. Stability of the
      liposomes was evaluated for three months at different storage conditions. In
      vitro skin permeation studies and confocal laser microscopy were performed to
      evaluate adapalene permeation in pig ear skin and hair follicles. RESULTS: The
      optimized process and formulation parameters resulted in homogeneous population
      of liposomes with a diameter of 86.66 +/- 3.5 nm in diameter and encapsulation
      efficiency of 97.01 +/- 1.84% w/w. In vitro permeation studies indicated
      liposomal formulation delivered more drug (6.72 +/- 0.83 MUg/cm(2)) in hair
      follicles than gel (3.33 +/- 0.26 MUg/cm(2)) and drug solution (1.62 +/- 0.054
      MUg/cm(2)). Drug concentration delivered to the skin layers was also enhanced
      compared to other two formulations. Confocal microscopy images confirmed drug
      penetration in the hair follicles when delivered using the liposomal formulation.
      CONCLUSION: Adapalene was efficiently encapsulated in liposomes and led to
      enhanced delivery in hair follicles, the desired target site for acne.

PMID- 27031917
TI  - See through ECG technology during cardiopulmonary resuscitation to analyze rhythm
      and predict defibrillation outcome.
AB  - PURPOSE OF REVIEW: Automated external defibrillators require preshock
      interruptions in cardiopulmonary resuscitation (CPR) to perform rhythm analysis.
      Artifact filtering technology may provide the opportunity to visualize the
      underlying ECG trace during CPR. Moreover, a continuous ventricular fibrillation
      analysis may be performed such to prioritize CPR interventions, that is, chest
      compression or defibrillation. RECENT FINDINGS: Different ECG filtering
      techniques and ventricular fibrillation analysis algorithms to predict
      defibrillation outcome have been developed. Techniques to analyze ECG rhythm
      during CPR encompass two major solutions: adaptive filters for the suppression of
      chest compression artifacts and algorithms for a direct analysis of the artifact
      contaminated ECG. The above methods achieve overall a high sensitivity of more
      than 99%, but an unacceptable specificity of less than 93%. Among the different
      ventricular fibrillation analysis approaches and defibrillation predictors,
      amplitude spectrum area has appeared as an independent predictor of
      defibrillation success, with an area under the receiver operating curve of 0.86.
      SUMMARY: The feasibility of ventricular fibrillation detection during CPR is a
      challenging issue that, if solved, would enable CPR to continue during the
      automated external defibrillator rhythm analysis. Furthermore, it would allow a
      continuous ventricular fibrillation analysis to optimize the timing of
      defibrillation and maximize the shock success.

PMID- 27031918
TI  - Thermophysical properties of LiCoO2-LiMn2O4 blended electrode materials for Li
      ion batteries.
AB  - Thermophysical properties of two cathode types for lithium-ion batteries were
      measured by dependence on temperature. The cathode materials are commercial
      composite thick films containing LiCoO2 and LiMn2O4 blended active materials,
      mixed with additives (binder and carbon black) deposited on aluminium current
      collector foils. The thermal diffusivities of the cathode samples were measured
      by laser flash analysis up to 673 K. The specific heat data was determined based
      on measured composite specific heat, aluminium specific heat data and their
      corresponding measured mass fractions. The composite specific heat data was
      measured using two differential scanning calorimeters over the temperature range
      from 298 to 573 K. For a comprehensive understanding of the blended composite
      thermal behaviour, measurements of the heat capacity of an additional LiMn2O4
      sample were performed, and are the first experimental data up to 700 K. Thermal
      conductivity of each cathode type and their corresponding blended composite
      layers were estimated from the measured thermal diffusivity, the specific heat
      capacity and the estimated density based on metallographic methods and structural
      investigations. Such data are highly relevant for simulation studies of thermal
      management and thermal runaway in lithium-ion batteries, in which the bulk
      properties are assumed, as a common approach, to be temperature independent.

PMID- 27031919
TI  - Response surface methodology investigation into the interactions between arsenic
      and humic acid in water during the coagulation process.
AB  - Interactions between arsenic and natural organic matter (NOM) are key limiting
      factors during the optimisation of drinking water treatment when significant
      amounts of both must be removed. This work uses Response Surface Methodology
      (RSM) to investigate how they interact during their simultaneous removal by iron
      chloride coagulation, using humic acid (HA) as a model NOM substance. Using a
      three factor Box-Behnken experimental design, As and HA removals were modelled,
      as well as a combined removal response. ANOVA results showed the significance of
      the coagulant dose for all three responses. At high initial arsenic
      concentrations (200MUg/l), As removal was significantly hindered by the presence
      of HA. In contrast, the HA removal response was found to be largely independent
      of the initial As concentration, with the optimum coagulant dose increasing at
      increasing HA concentrations. The combined response was similar to the HA removal
      response, and the interactions evident are most interesting in terms of
      optimising treatment processes during the preparation of drinking water,
      highlighting the importance of utilizing RSM for such investigations. The
      combined response model was successfully validated with two different
      groundwaters used for drinking water supply in the Republic of Serbia, showing
      excellent agreement under similar experimental conditions.

PMID- 27031920
TI  - Investigation of the effect of nanoparticle exposure on the flocculability of
      activated sludge using particle image velocimetry in combination with the
      extended DLVO analysis.
AB  - With the application of nanotechnologies, nanoparticles (NPs) may enter the
      wastewater collection system, threatening the operation and stability of the
      treatment process. The present study investigated the effect of short-term
      exposures of activated sludge (AS) to NPs on the sludge flocculation ability.
      Three types of NPs, ZnO, TiO2 and SiO2, were used at a concentration level of
      100mg/L for the 24-h exposure, and the particle image velocimetry (PIV)
      technology was employed to track the sludge flocculation dynamics during the
      tests. The results showed that a short-term exposure of the AS to NPs did not
      cause deterioration of the sludge in treatment performance and flocculation.
      According to the PIV detections, the flocculability of the AS actually was
      enhanced to some extent after the short-term NPs exposure. Flocs formed after the
      NPs exposure became more fractal with an elongated shape and a rougher surface,
      as a result of the improved cell attachment. The extended DLVO theory in
      combination with the thermodynamic analysis can be well applied to describe the
      enhanced AS flocculation after the NPs exposure. It is apparent that the
      attachment of NPs onto cells and flocs can effectively reduce the interaction
      energy barriers, leading to their improved flocculation ability. 

PMID- 27031921
TI  - A dual-mode signaling response of a AuNP-fluorescein based probe for specific
      detection of thiourea.
AB  - By employing fluorescein and AuNPs as energy donors and acceptors, respectively,
      a novel fluorescence resonance energy transfer (FRET)-based dual-mode sensor for
      selective recognition and quantitative detection of thiourea was designed and
      constructed in this study for the first time. Herein, it is demonstrated that
      fluorescein could be adsorbed on the surface of AuNPs and induce fluorescence
      quenching through the well-known FRET process. The preferential introduction of
      thiourea would reduce the overall surface negative charges of AuNPs by replacing
      the original citrate groups, leading to the aggregation of AuNPs. Meanwhile,
      thiourea could prevent the binding between fluorescein and AuNPs, reduce the as
      formed FRET effect, and then lead to fluorescence recovery of the fluorescein.
      Therefore, a dual-mode sensor with AuNP-related colorimetric and fluorescein
      based fluorescence readout was rationally developed. Under the optimum
      conditions, the detection limits were calculated to be 10 nM and 23 nM for
      fluorescent and colorimetric sensors, individually, and a limit of 0.4 MUM was
      detected by the naked eye. Finally, such a simple, convenient, cost-effective,
      highly selective and sensitive sensing assay was successfully applied in the
      detection of thiourea in tap water and fruit juice samples. 

PMID- 27031922
TI  - Characterization of mAb dimers reveals predominant dimer forms common in
      therapeutic mAbs.
AB  - The formation of undesired high molecular weight species such as dimers is an
      important quality attribute for therapeutic monoclonal antibody formulations.
      Therefore, the thorough understanding of mAb dimerization and the detailed
      characterization mAb dimers is of great interest for future pharmaceutical
      development of therapeutic antibodies. In this work, we focused on the analyses
      of different mAb dimers regarding size, surface properties, chemical identity,
      overall structure and localization of possible dimerization sites. Dimer
      fractions of different mAbs were isolated to a satisfactory purity from bulk
      material and revealed 2 predominant overall structures, namely elongated and
      compact dimer forms. The elongated dimers displayed one dimerization site
      involving the tip of the Fab domain. Depending on the stress applied, these
      elongated dimers are connected either covalently or non-covalently. In contrast,
      the compact dimers exhibited non-covalent association. Several interaction points
      were detected for the compact dimers involving the hinge region or the base of
      the Fab domain. These results indicate that mAb dimer fractions are rather
      complex and may contain more than one kind of dimer. Nevertheless, the overall
      appearance of mAb dimers suggests the existence of 2 predominant dimeric
      structures, elongated and compact, which are commonly present in preparations of
      therapeutic mAbs.

PMID- 27031923
TI  - Inter-observer reliability of the HERDOO2 clinical decision rule.

PMID- 27031924
TI  - Posttraumatic growth in aging individuals who have lost their only child in
      China.
AB  - This article examined the extent of posttraumatic growth (PTG) and factors
      related to PTG in aging individuals who have lost their only child in China. The
      sample included 201 bereaved parents from different families residing in
      Chongqing, China. They were between 49-80 years old (M = 61) and had lost their
      only child. Personal interviews were conducted in their homes. PTG was assessed
      with a revised Posttraumatic Growth Inventory (PTGI-R). Descriptive and multiple
      linear regression analyses were conducted. Overall, the sample showed a positive
      tendency toward PTG. The older the child was at death, the less PTG the parent
      experienced. Time since the child's death was negatively correlated with PTG, and
      parents whose children died by accident/suicide had lower PTG than those whose
      children died of illness. Lower education and poor parental health were
      significantly associated with lower levels of PTG. Community support was
      significantly and positively associated with PTG. A majority of aging parents who
      have lost their only child in China experience PTG. Characteristics related to
      the loss (child's age at death, time since the death, and cause of death),
      personal resources (parent's education and health), and community support are
      associated with the degree of growth.

PMID- 27031925
TI  - Asymmetric Synthesis and Binding Study of New Long-Chain HPA-12 Analogues as
      Potent Ligands of the Ceramide Transfer Protein CERT.
AB  - A series of 12 analogues of the Cer transfer protein (CERT) antagonist HPA-12
      with long aliphatic chains were prepared as their (1R,3S)-syn and (1R,3R)-anti
      stereoisomers from pivotal chiral oxoamino acids. The enantioselective access to
      these intermediates as well as their ensuing transformation relied on a practical
      crystallization-induced asymmetric transformation (CIAT) process. Sonogashira
      coupling followed by triple bond reduction and thiophene ring
      hydrodesulfurization (HDS) into the corresponding alkane moieties was then
      implemented to complete the synthetic routes delivering the targeted HPA-12
      analogues in concise 4- to 6-step reaction sequences. Ten compounds were
      evaluated regarding their ability to bind to the CERT START domain by using the
      recently developed time-resolved FRET-based homogeneous (HTR-FRET) binding assay.
      The introduction of a lipophilic appendage on the phenyl moiety led to an overall
      10- to 1000-fold enhancement of the protein binding, with the highest effect
      being observed for a n-hexyl residue in the meta position. The importance of the
      phenyl ring for the activity was indicated by the reduced potency of the 3
      deoxyphytoceramide aliphatic analogues. The 1,3-syn stereoisomers were
      systematically more potent than their 1,3-anti analogues. In silico studies were
      used to rationalized these trends, leading to a model of protein recognition
      coherent with the stronger binding of (1R,3S)-syn HPAs. 

PMID- 27031926
TI  - Beyond Mg(2+): functional interactions between RNA and transition metals.
AB  - It is well-known that RNA structure and function depend heavily on cations, and
      the ability of Mg(2+) to stabilize RNA structures has been emphasized. Recent
      studies, however, highlight the importance of transition metals in RNA function.
      Riboswitches that selectively bind Ni(2+), Co(2+), and Mn(2+) have been
      discovered with specific RNA-metal sites that influence metal-related gene
      expression. Exogenous metals such as Pt(II) from therapeutics also bind and may
      inhibit cellular RNA. Novel reports that RNA can host Fe(II) in catalytic sites
      are relevant to early life in pre-oxygenic atmospheres. These new observations
      emphasize the importance of transition metals in the field of RNA
      metallobiochemistry.

PMID- 27031927
TI  - Recent advances in designed coiled coils and helical bundles with inorganic
      prosthetic groups-from structural to functional applications.
AB  - Recent contributions to the de novo design of metalloproteins based on coiled
      coils and helical bundles are described herein, with examples covering
      mononuclear, multinuclear, and metallo-porphyrin sites, as well as membrane
      soluble designs. Important progress is being made in the field with a diverse
      range of functionalities, sometimes beyond those found in biology, being
      successfully engineered into these simplified scaffolds and represents an
      exciting prospect for the future.

PMID- 27031928
TI  - In vivo xenogeneic scaffold fate is determined by residual antigenicity and
      extracellular matrix preservation.
AB  - The immunological potential of animal-derived tissues and organs is the critical
      hurdle to increasing their clinical implementation. Glutaraldehyde-fixation cross
      links proteins in xenogeneic tissues (e.g., bovine pericardium) to delay immune
      rejection, but also compromises the regenerative potential of the resultant
      biomaterial. Unfixed xenogeneic biomaterials in which xenoantigenicity has been
      ameliorated and native extracellular matrix (ECM) architecture has been
      maintained have the potential to overcome limitations of current clinically
      utilized glutaraldehyde-fixed biomaterials. The objective of this work was to
      determine how residual antigenicity and ECM architecture preservation modulate
      recipient immune and regenerative responses towards unfixed bovine pericardium
      (BP) ECM scaffolds. Disruption of ECM architecture during scaffold generation,
      with either SDS-decellularization or glutaraldehyde-fixation, stimulated
      recipient foreign body response and resultant fibrotic encapsulation following
      leporine subpannicular implantation. Conversely, BP scaffolds subjected to
      stepwise removal of hydrophilic and lipophilic antigens using amidosulfobetaine
      14 (ASB-14) maintained native ECM architecture and thereby avoided fibrotic
      encapsulation. Removal of hydrophilic and lipophilic antigens significantly
      decreased local and systemic graft-specific, adaptive immune responses and
      subsequent calcification of BP scaffolds compared to scaffolds undergoing
      hydrophile removal only. Critically, removal of antigenic components and
      preservation of ECM architecture with ASB-14 promoted full-thickness recipient
      non-immune cellular repopulation of the BP scaffold. Further, unlike clinically
      utilized fixed BP, ASB-14-treated scaffolds fostered rapid intimal and medial
      vessel wall regeneration in a porcine carotid patch angioplasty model. This work
      highlights the importance of residual antigenicity and ECM architecture
      preservation in modulating recipient immune and regenerative responses towards
      xenogeneic biomaterial generation. 

PMID- 27031929
TI  - Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided
      photothermal therapy.
AB  - Along with intrinsic magnetic resonance imaging (MRI) advantages, iron oxide
      nanomaterials capable of photothermal conversion have been reported very recently
      and have again raised great interest in their designs among biomedical
      researchers. However, like other inorganic nanomaterials, high macrophage uptake,
      short blood retention time and unfavorable biodistributions have strongly
      hampered their applications in vivo. To solve these problems, a rational design
      of red blood cell (RBC) membrane camouflaged iron oxide magnetic clusters
      (MNC@RBCs) is presented in this paper. Our data show that by simply introducing
      an "ultra-stealth" biomimetic coating to iron oxide magnetic nanoclusters (MNCs),
      MNC@RBCs maintain the imaging and photothermal functionalities inherited from
      MNCs cores while achieving much lower nonspecific macrophage uptake and
      dramatically altered fate in vivo. MNC@RBCs with superior prolonged blood
      retention time, preferred high tumor accumulation and relatively lowered liver
      biodistribution are demonstrated when injected intravenously in mice, leading to
      greatly enhanced photothermal therapeutic efficacy by a single treatment without
      further magnetic force manipulation. Our study illustrates a well prepared
      integration of MNCs and RBCs, exploiting advantages of both functionalities
      within a single unit and suggests a promising future for iron-based nanomaterials
      application in vivo.

PMID- 27031930
TI  - Fabrication of dual responsive co-delivery system based on three-armed peptides
      for tumor therapy.
AB  - Introducing drugs into gene delivery systems to fabricate co-delivery systems for
      synergy therapy has become a promising strategy for tumor therapy. In this study,
      a dual responsive co-delivery system RHD/p53 was fabricated to enhance the
      antitumor efficacy with a low dose of doxorubicin (DOX). The reducible branched
      cationic polypeptide (RBCP), which was cross-linked via the thiol groups of two
      three-armed cationic peptides (CRR)2KRRC and (CHH)2KHHC, was designated as RH.
      Then, DOX was immobilized on RH via pH-sensitive hydrazone bonds to obtain RHD.
      The positively charged RHD could compress p53 plasmid to form RHD/p53 complexes.
      After RHD/p53 complexes accumulated in tumor sites, the ability of cell
      penetrating by cationic peptide (CRR)2KRRC would facilitate the cellular
      internalization of complexes. Then, the complexes would be trapped in endosome,
      and the cleavage of hydrazone bonds in the intracellular acidic endosome could
      lead to pH-induced release of DOX. Additionally, the ability of protonation by
      (CHH)2KHHC could promote the escape of complexes from endosome to cytoplasm. Due
      to the cleavage of disulfide bonds triggered by the high-content GSH in
      cytoplasm, the complexes would be degraded and released p53 for co-therapy to
      improve antitumor efficacy. Both in vitro and in vivo studies indicated that dual
      responsive co-delivery system RHD/p53 could enhance antitumor efficacy, which
      provides a useful strategy for co-delivery of different therapeutic agents in
      tumor treatment.

PMID- 27031932
TI  - Dynamic penile peak systolic velocity predicts major adverse cardiovascular
      events in hypertensive patients with erectile dysfunction.
AB  - OBJECTIVE: Hypertension is associated with an abnormal penile blood flow. Reduced
      dynamic penile peak systolic velocity (D-PSV) correlates with adverse
      cardiovascular outcomes. The aim of this study is to investigate whether abnormal
      penile blood flow predicts major adverse cardiovascular events (MACE) in
      hypertensive men. METHODS: In total, 298 hypertensive men (55 +/- 9 y/o) without
      known cardiovascular disease or diabetes were evaluated for cavernous vascular
      disease severity by dynamic penile Doppler ultrasound. The whole population was
      divided into tertiles according to D-PSV reduction (low tertile <25 cm/s; middle
      tertile 25-35 cm/s; and high tertile >35 cm/s). Predictive performance was
      evaluated with calibration, discrimination, and reclassification. RESULTS: During
      the mean follow-up period of 4.9 years, a total of 22 (7%) MACE occurred. D-PSV
      level was associated with MACE and the differences between the tertiles were
      significant (Mantel log-rank test: 6.54; P < 0.01). A Cox proportional hazard
      model showed that study participants in the lowest D-PSV tertile (<25 cm/s) had
      an approximately 3.5-fold higher MACE risk compared with those in the highest D
      PSV tertile (>35 cm/s) after adjustment for age, systolic pressure, metabolic
      parameters, smoking, C-reactive protein, and testosterone levels. Low D-PSV did
      not significantly improve the C-statistic model (0.774 vs. 0.767; P = 0.44),
      whereas the calibration was satisfactory (Hosmer-Lemeshow X = 8.73, P = 0.30).
      When only intermediate-risk patients were evaluated, the risk reclassification
      beyond traditional risk factors resulted in a clinical net reclassification index
      of 9.2% that was marginally significant (P = 0.07). The integrated discrimination
      improvement index showed better performance of the model that included D-PSV
      compared with the reference model in identifying MACE (improvement index: 0.047,
      P = 0.038). CONCLUSION: Low-penile blood flow predicts MACE in hypertensive
      patients free of clinical atherosclerosis. This predictive ability is independent
      of the severity of hypertension and decreased testosterone that is often present
      in such patients.

PMID- 27031931
TI  - Dynamic culture improves cell reprogramming efficiency.
AB  - Cell reprogramming to pluripotency is an inefficient process and various
      approaches have been devised to improve the yield of induced pluripotent stem
      cells. However, the effect of biophysical factors on cell reprogramming is not
      well understood. Here we showed that, for the first time, dynamic culture with
      orbital shaking significantly improved the reprogramming efficiency in adherent
      cells. Manipulating the viscosity of the culture medium suggested that the
      improved efficiency is mainly attributed to convective mixing rather than
      hydrodynamic shear stress. Temporal studies demonstrated that the enhancement of
      reprogramming efficiency required the dynamic culture in the middle but not early
      phase. In the early phase, fibroblasts had a high proliferation rate, but as the
      culture became over-confluent in the middle phase, expression of p57 was
      upregulated to inhibit cell proliferation and consequently, cell reprogramming.
      Subjecting the over confluent culture to orbital shaking prevented the
      upregulation of p57, thus improving reprogramming efficiency. Seeding cells at
      low densities to avoid over-confluency resulted in a lower efficiency, and
      optimal reprogramming efficiency was attained at a high seeding density with
      dynamic culture. Our findings provide insight into the underlying mechanisms of
      how dynamic culture condition regulate cell reprogramming, and will have broad
      impact on cell engineering for regenerative medicine and disease modeling. 

PMID- 27031933
TI  - Diagnostic accuracy of aldosterone and renin measurement by chemiluminescent
      immunoassay and radioimmunoassay in primary aldosteronism.
AB  - OBJECTIVE: Up to 50% of hypertensive patients should be screened for primary
      aldosteronism, using the aldosterone to renin (or plasma renin activity) ratio
      [aldosterone to active renin ratio (AARR) and aldosterone to plasma renin
      activity ratio (ARR), respectively]. Aim of the study was to prospectively
      compare the diagnostic accuracy of AARR (measured by chemiluminescent
      immunoassay) and ARR (measured by radioimmunoassay) as screening tests for
      primary aldosteronism and aldosterone assays (measured by chemiluminescence and
      radioimmunoassay) during confirmatory testing. METHODS: One hundred patients were
      screened for primary aldosteronism and 34 underwent confirmatory testing. The cut
      offs for ARR and AARR were 30 ng/dl/ng/ml/h and 3.7 ng/dl/mU/l, respectively.
      Patients with positive confirmatory test underwent subtype diagnosis. RESULTS:
      Seventy-five patients were essential hypertensive patients, 15 had idiopathic
      hyperaldosteronism, five aldosterone-producing adenoma (APA) and five with
      undefined diagnosis. The AARR displayed a sensitivity of 90% and a specificity of
      99%, the ARR had a sensitivity of 100% and a specificity of 73%. Of the two of 20
      primary aldosteronism patients missed by AARR, none resulted affected by APA. All
      primary aldosteronism patients were correctly diagnosed by chemiluminescence at
      confirmatory testing. In the total sample of 168 measurements both the
      correlation for plasma renin activity with renin and for aldosterone in
      chemiluminescence and radioimmunoassay were highly significant (rho = 0.70, P <
      0.001 and rho = 0.78, P < 0.001, respectively). On receiver operator
      characteristics curves, the area under the curve for AARR was 0.989 [95%
      confidence interval (CI) 0.97-1] and 0.934 for ARR (95% CI 0.89-0.98), which were
      not significantly different. CONCLUSION: The automated aldosterone and renin
      chemiluminescent assay is a reliable alternative to the radioimmunometric method,
      especially for APA detection.

PMID- 27031934
TI  - Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular
      myogenic tone via G protein-coupled receptor 7: Erratum.

PMID- 27031935
TI  - Percutaneous Extracorporeal Membrane Oxygenation: The Newest Iteration of
      Temporary Mechanical Support for the Left Ventricle.

PMID- 27031936
TI  - Percutaneous Coronary Intervention in Severely Calcified Unprotected Left Main
      Coronary Artery Disease: Initial Experience With Orbital Atherectomy.
AB  - OBJECTIVE: We report the clinical outcomes of patients who underwent percutaneous
      coronary intervention (PCI) with orbital atherectomy for severely calcified
      unprotected left main coronary artery (ULMCA) disease. BACKGROUND: Although
      surgical revascularization is the gold standard for patients with ULMCA disease,
      not all patients are candidates for this. PCI is increasingly used to treat
      complex coronary artery disease, including ULMCA disease. The presence of
      severely calcified lesions increases the complexity of PCI. Orbital atherectomy
      can be used to facilitate stent delivery and expansion in severely calcified
      lesions. The clinical outcomes of patients treated with orbital atherectomy for
      severely calcified ULMCA disease have not been reported. METHODS: From May 2014
      to July 2015, a total of 14 patients who underwent PCI with orbital atherectomy
      for ULMCA disease were retrospectively evaluated. The primary endpoint was major
      cardiac and cerebrovascular event (cardiac death, myocardial infarction, stroke,
      and target-lesion revascularization) at 30 days. RESULTS: The mean age was 78.2
      +/- 5.8 years. The mean ejection fraction was 41.8 +/- 19.8%. Distal bifurcation
      disease was present in 9 of 14 patients. Procedural success was achieved in all
      14 patients. The 30-day major adverse cardiac and cerebrovascular event rate was
      0%. One patient had coronary dissection that was successfully treated with
      stenting. No patient had perforation, slow flow, or thrombosis. CONCLUSIONS:
      Orbital atherectomy in patients with severely calcified ULMCA disease is
      feasible, even in high-risk patients who were considered poor surgical
      candidates. Randomized trials are needed to determine the role of orbital
      atherectomy in ULMCA disease.

PMID- 27031937
TI  - Spontaneous Echocardiographic Contrast in the Left Atrium During Transcatheter
      Aortic Valve Replacement is Associated With Worse Outcomes.
AB  - OBJECTIVES: Patients undergoing transcatheter aortic valve replacement (TAVR)
      often have spontaneous echocardiographic contrast (SEC) observed in the left
      atrium (LA). Mid-term prognosis of patients with SEC following TAVR is not well
      studied. We assessed the impact of SEC on outcomes after TAVR. METHODS: Medical
      records of 93 consecutive patients who underwent TAVR at a single center were
      reviewed retrospectively. The primary endpoint was defined as the composite of a
      cardioembolic event, death from any cause, and admission for decompensated heart
      failure within 3 months of TAVR. RESULTS: After excluding 3 patients who had
      procedural complications, 90 patients were included in the study. The mean age
      was 81 +/- 8 years old and 50% were male. There were 12 patients with SEC in the
      LA (group 1) and 78 patients without SEC in the LA (group 2) during the TAVR
      procedure. Atrial fibrillation was more common in group 1 (50% vs 13%,
      respectively; P=.01) and diabetes was more common in group 2 (17% vs 53%,
      respectively; P=.03). The primary endpoint occurred in 22 patients (24%) and
      occurred more in group 1 (58% vs 19%, respectively; P<.01). On regression
      analysis, after adjusting for sex and STS score, SEC had a hazard ratio (HR) of
      5.02 (95% confidence interval [CI], 1.96-12.9; P<.001) and STS >=15 had an HR of
      6.37 (95% CI, 2.02-20.1; P=.01). On survival analysis, group 1 had lower event
      free survival compared with group 2 (log-rank P=.01). CONCLUSION: SEC during TAVR
      procedure is a negative prognostic marker for death, cardioembolic events, or
      admission for decompensated heart failure in the first 3 months post procedure.

PMID- 27031938
TI  - Spontaneous Echo Contrast and TAVR: A Smoking Gun?

PMID- 27031939
TI  - Side-Branch Occlusions in Coronary CTO-PCI: Avoid or Forget?

PMID- 27031940
TI  - Balloon-Assisted Microdissection "BAM" Technique for Balloon-Uncrossable Chronic
      Total Occlusions.
AB  - BACKGROUND: After successful guidewire passage, failure to cross the occluded
      segment with a balloon is the most common cause of procedural failure in coronary
      chronic total occlusion (CTO) intervention. We evaluated the safety and efficacy
      of the balloon-assisted microdissection (BAM) technique for treating these
      complex balloon-uncrossable lesions. METHODS: We identified consecutive cases
      treated with BAM for balloon-uncrossable CTOs between January 2012 and February
      2015 at two experienced CTO percutaneous coronary intervention (PCI) centers and
      reviewed their clinical and angiographic characteristics and procedural outcomes.
      RESULTS: During the study period, a total of 17 patients had BAM performed for
      balloon-uncrossable CTOs. Mean age was 65.5 +/- 8.7 years and 94% of patients
      were males who often had prior myocardial infarction, PCI, and coronary artery
      bypass graft surgery. The most common CTO target vessel was the right coronary
      artery. Mean J-CTO score was 2.6 +/- 1.1. Despite high lesion complexity, overall
      procedural success was 94% and BAM facilitated success in approximately one-half
      of these cases. All BAM failure cases except 1 were successfully recanalized
      utilizing additional techniques. No patient experienced a major complication.
      CONCLUSION: BAM is a simple, inexpensive, and safe technique that can facilitate
      crossing of balloon-uncrossable CTOs and can be considered as first-line
      treatment for these complex lesions.

PMID- 27031941
TI  - A Paradigm Shift Toward Forearm Arterial Access Requires Establishing
      Preprocedure Adequacy of Hand Collateralization or Patency of Collateralizing
      Forearm Arteries.

PMID- 27031942
TI  - Prototype Systems Containing Human Cytochrome P450 for High-Throughput Real-Time
      Detection of DNA Damage by Compounds That Form DNA-Reactive Metabolites.
AB  - The formation of reactive metabolites through biotransformation is the suspected
      cause of many adverse drug reactions. Testing for the propensity of a drug to
      form reactive metabolites has increasingly become an integral part of lead
      optimization strategy in drug discovery. DNA reactivity is one undesirable facet
      of a drug or its metabolites and can lead to increased risk of cancer and
      reproductive toxicity. Many drugs are metabolized by cytochromes P450 in the
      liver and other tissues, and these reactions can generate hard electrophiles.
      These hard electrophilic reactive metabolites may react with DNA and may be
      detected in standard in vitro genotoxicity assays; however, the majority of these
      assays fall short due to the use of animal-derived organ extracts that
      inadequately represent human metabolism. The current study describes the
      development of bacterial systems that efficiently detect DNA-damaging
      electrophilic reactive metabolites generated by human P450 biotransformation.
      These assays use a GFP reporter system that detects DNA damage through induction
      of the SOS response and a GFP reporter to control for cytotoxicity. Two human
      CYP1A2-competent prototypes presented here have appropriate characteristics for
      the detection of DNA-damaging reactive metabolites in a high-throughput manner.
      The advantages of this approach include a short assay time (120-180 min) with
      real-time measurement, sensitivity to small amounts of compound, and adaptability
      to a microplate format. These systems are suitable for high-throughput assays and
      can serve as prototypes for the development of future enhanced versions.

PMID- 27031943
TI  - Update: Interim Guidance for Health Care Providers Caring for Women of
      Reproductive Age with Possible Zika Virus Exposure--United States, 2016.
AB  - CDC has updated its interim guidance for U.S. health care providers caring for
      women of reproductive age with possible Zika virus exposure to include
      recommendations on counseling women and men with possible Zika virus exposure who
      are interested in conceiving. This guidance is based on limited available data on
      persistence of Zika virus RNA in blood and semen. Women who have Zika virus
      disease should wait at least 8 weeks after symptom onset to attempt conception,
      and men with Zika virus disease should wait at least 6 months after symptom onset
      to attempt conception. Women and men with possible exposure to Zika virus but
      without clinical illness consistent with Zika virus disease should wait at least
      8 weeks after exposure to attempt conception. Possible exposure to Zika virus is
      defined as travel to or residence in an area of active Zika virus transmission (
      http://www.cdc.gov/zika/geo/active-countries.html), or sex (vaginal intercourse,
      anal intercourse, or fellatio) without a condom with a man who traveled to or
      resided in an area of active transmission. Women and men who reside in areas of
      active Zika virus transmission should talk with their health care provider about
      attempting conception. This guidance also provides updated recommendations on
      testing of pregnant women with possible Zika virus exposure. These
      recommendations will be updated when additional data become available.

PMID- 27031944
TI  - Influence of different fixation protocols on the preservation and dimensions of
      cardiac tissue.
AB  - Recent extensive progress in invasive cardiac procedures has triggered a wave of
      dozens of heart morphometric anatomical studies that are carried out largely
      using autopsied samples fixed in formaldehyde solution prior to observations and
      measurements. In reality, very little is known about changes in heart tissue
      dimensions during fixation. The aim of this study was therefore to investigate
      how fixation affects the dimensions of cardiac tissue, and if different types and
      concentrations of reagents affect this phenomenon. A total of 40 pig heart
      samples were investigated, and seven different measuring sites were permanently
      marked in every heart prior to fixation. Four study groups (n = 10 each) were
      assembled that differed only in concentration and the type of fixative: (i) 2%
      formaldehyde solution; (ii) 4% formaldehyde solution (formalin); (iii) 10%
      formaldehyde solution; (iv) alcoholic formalin. The samples were measured before
      and after fixation at the following time points: 24 h, 72 h and 168 h. It was
      found that different fixatives significantly affected different parameters.
      Almost all of the heart dimensions that were measured stabilized after 24 h;
      later changes were statistically insignificant in the point-to-point comparison.
      Change in the length of the interatrial septum surface was not altered
      significantly in any of the fixatives after 24 h of preservation. It was found
      that 10% formaldehyde increased the thickness of muscular tissue only after 24 h;
      this thickening was reduced after 72 h and was insignificant at 168 h. Other
      heart parameters in this group do not present significant changes over the entire
      fixation time duration. In conclusion, the 10% formaldehyde phosphate-buffered
      solution appeared to be the best fixative among the fixatives that were studied
      for cardiac morphometric purposes; this solution caused the smallest changes in
      tissue dimensions. Measurements should be obtained at least after 1 week of
      preservation when most parameters exhibit the smallest changes compared with the
      non-preserved samples.

PMID- 27031945
TI  - Osteophyte formation after ACL rupture in mice is associated with joint
      restabilization and loss of range of motion.
AB  - Osteophytes are a typical radiographic finding during osteoarthritis (OA).
      Osteophytes are thought to form in response to joint instability; however, the
      time course of osteophyte formation and joint stabilization following joint
      injury is not well understood. In this study, we investigated the time course of
      osteophyte formation and joint function following non-invasive knee injury in
      mice. We hypothesized that initial joint instability following knee injury would
      initiate osteophyte formation, which would in turn restabilize the joint and
      reduce range of motion (ROM). Mice were subjected to non-invasive anterior
      cruciate ligament (ACL) rupture. Anterior-posterior (AP) joint laxity, ROM, and
      chondro/osteophyte formation were measured immediately after injury, and 2, 4, 6,
      and 8 weeks post-injury. Chondrophyte areas at each time point were measured with
      histology, while mineralized osteophyte volume was determined using micro
      computed tomography. Immediately after ACL rupture, AP joint laxity was increased
      twofold, while ROM was increased 11.7%. Chondrophytes appeared by 2 weeks post
      injury, corresponding with a decrease in AP joint laxity and ROM. By 8 weeks post
      injury, considerable osteophyte formation was observed around the joint, AP joint
      laxity returned to control levels, and joint ROM decreased to 61% of control
      values. These data support a role for chondro/osteophytes in joint
      restabilization after injury, and provide crucial insight into the time course
      and pathology of joint degeneration during OA development in the mouse. Statement
      of Clinical Significance: Results from this study increase understanding of
      conditions leading to osteophyte formation.(c) 2016 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 35:466-473, 2017.

PMID- 27031946
TI  - Counteraction of Trehalose on N, N-Dimethylformamide-Induced Candida rugosa
      Lipase Denaturation: Spectroscopic Insight and Molecular Dynamic Simulation.
AB  - Candida rugosa lipase (CRL) has been widely used as a biocatalyst for non-aqueous
      synthesis in biotechnological applications, which, however, often suffers
      significant loss of activity in organic solvent. Experimental results show that
      trehalose could actively counteract the organic-solvent-induced protein
      denaturation, while the molecular mechanisms still don't unclear. Herein, CRL was
      used as a model enzyme to explore the effects of trehalose on the retention of
      enzymatic activity upon incubation in N,N-dimethylformamide (DMF). Results showed
      that both catalytic activity and conformation changes of CRL influenced by DMF
      solvent were inhibited by trehalose in a dose-dependent fashion. The simulations
      further indicated that the CRL protein unfolded in binary DMF solution, but
      retained the native state in the ternary DMF/trehalose system. Trehalose as the
      second osmolyte added into binary DMF solution decreased DMF-CRL hydrogen bonds
      efficiently, whereas increased the intermolecular hydrogen bondings between DMF
      and trehalose. Thus, the origin of its denaturing effects of DMF on protein is
      thought to be due to the preferential exclusion of trehalose as well as the
      intermolecular hydrogen bondings between trehalose and DMF. These findings
      suggest that trehalose protect the CRL protein from DMF-induced unfolding via
      both indirect and direct interactions. 

PMID- 27031948
TI  - Is It Acute Stroke or Not - A Prospective Observational Study from a
      Multidisciplinary Emergency Department.
AB  - BACKGROUND: Acute stroke is a medical emergency with various clinical
      presentations. Since the introduction of systemic thrombolytic treatment, stroke
      diagnosis has been made quickly and with great caution, and the trend of rapid
      presentation at hospitals has increased. METHODS: In our multidisciplinary
      Emergency Department, we prospectively collected and analysed data of consecutive
      patients presenting with suspected acute stroke (SAS) or transient ischemic
      attack (TIA). RESULTS: Four hundred ten patients (200 men, mean age 68 +/- 16,
      range 17-93 years) with SAS were admitted of which 105 were prehospitally
      announced as within the time-window for thrombolytic treatment (TW). Diagnosis of
      acute stroke/TIA was retained in 147 (35.9%). The initially reported TW <4.5 h
      was wrong in 35.3%. Thrombolysis was performed in 27 patients (23.5% of ischemic
      stroke patients; 6.6% of all SAS). Diagnosis of another neurologic disease was
      made in 62 (15.1%). Major differential diagnoses came from the field of internal
      medicine, psychiatry or otorhinolaryngology. One hundred fifty patients (36.6%)
      were rapidly discharged. CONCLUSION: About half the number of our patients
      admitted for SAS did not suffer from an acute neurologic disease. Residual
      symptoms post-stroke might be partly responsible for initial misinterpretation.
      The crucial difference between symptom onset and symptom recognition needs to be
      emphasized to improve the prehospital assessment of the TW.

PMID- 27031947
TI  - Quantitative and semi-quantitative measurements of axonal degeneration in tissue
      and primary neuron cultures.
AB  - BACKGROUND: Axon viability is critical for maintaining neural connectivity, which
      is central to neural functionality. Many neurodegenerative diseases (e.g.,
      Parkinson's disease (PD) and Alzheimer's disease) appear to involve extensive
      axonal degeneration that often precedes somatic loss in affected neural
      populations. Axonal degeneration involves a number of intracellular pathways and
      characteristic changes in axon morphology (i.e., swelling, fragmentation, and
      loss). NEW METHOD: We describe a relatively simple set of methods to quantify the
      axonal degeneration using the 6-hydroxydopamine neurotoxin model of PD in rats
      and a colchicine-induced model in primary rat neurons. Specifically, approaches
      are described that use the spaceballs stereological probe for tissue sections and
      petrimetrics stereological probe for cultured neurons, and image analysis
      techniques in both tissue sections and cultured neurons. RESULTS: These methods
      provide a mechanism for obtaining quantitative and semi-quantitative data to
      track the extent of axonal degeneration and may prove useful as outcome measures
      in studies aimed at preventing or slowing axonal degeneration in disease models.
      COMPARISON WITH EXISTING METHODS: Existing methods of quantification of axonal
      degeneration use densitometry and manual counts of axonal projections, but they
      do not utilize the random, unbiased systematic sampling approaches that are
      characteristic of stereological methods. The ImageJ thresholding analyses
      described here provide a descriptive method for quantifying the state of axonal
      degeneration. CONCLUSIONS: These methods provide an efficient and effective means
      to quantify the extent and state of axonal degeneration in animal tissue and
      cultured neurons and can be used in other models for the same purposes.

PMID- 27031949
TI  - Dredging in the Spratly Islands: Gaining Land but Losing Reefs.
AB  - Coral reefs on remote islands and atolls are less exposed to direct human
      stressors but are becoming increasingly vulnerable because of their development
      for geopolitical and military purposes. Here we document dredging and filling
      activities by countries in the South China Sea, where building new islands and
      channels on atolls is leading to considerable losses of, and perhaps irreversible
      damages to, unique coral reef ecosystems. Preventing similar damage across other
      reefs in the region necessitates the urgent development of cooperative management
      of disputed territories in the South China Sea. We suggest using the Antarctic
      Treaty as a positive precedent for such international cooperation. 

PMID- 27031950
TI  - Memory-Like Antigen-Specific Human NK Cells from TB Pleural Fluids Produced IL-22
      in Response to IL-15 or Mycobacterium tuberculosis Antigens.
AB  - Our previous result indicated that memory-like human natural killer (NK) cells
      from TB pleural fluid cells (PFCs) produced large amounts of IFN-gamma in
      response to Bacille Calmette Guerin (BCG). Furthermore, recent studies have shown
      that human lymphoid tissues harbored a unique NK cell subset that specialized in
      production of interleukin (IL)-22, a proinflammatory cytokine that mediates host
      defense against pathogens. Yet little information was available with regard to
      the properties of IL-22 production by memory-like human NK cells. In the present
      study, we found that cytokines IL-15 induced and IL-12 enhanced the levels of IL
      22 by NK cells from TB PFCs. In addition, IL-22 but not IL-17 was produced by NK
      cells from PFCs in response to BCG and M.tb-related Ags. More importantly, the
      subset of specific IL-22-producing NK cells were distinct from IFN-gamma
      producing NK cells in PFCs. CD45RO+ or CD45RO- NK cells were sorted, co-cultured
      with autologous monocytes and stimulated with BCG for the production of IL-22.
      The result demonstrated that CD45RO+ but not CD45RO- NK cells produced
      significantly higher level of IL-22. Anti-IL-12Rbeta1 mAbs (2B10) partially
      inhibit the expression of IL-22 by NK cells under the culture with BCG.
      Consistently, BCG specific IL-22-producing NK cells from PFCs expressed
      CD45ROhighNKG2Dhighgranzyme Bhigh. In conclusion, our data demonstrated that
      memory-like antigen-specific CD45RO+ NK cells might participate in the recall
      immune response for M. tb infection via producing IL-22, which display a critical
      role to fight against M. tb. 

PMID- 27031951
TI  - The Sequence and Structure Determine the Function of Mature Human miRNAs.
AB  - Micro RNAs (miRNAs) (19-25 nucleotides in length) belong to the group of non
      coding RNAs are the most abundant group of posttranscriptional regulators in
      multicellular organisms. They affect a gene expression by binding of fully or
      partially complementary sequences to the 3'-UTR of target mRNA. Furthermore,
      miRNAs present a mechanism by which genes with diverse functions on multiple
      pathways can be simultaneously regulated at the post-transcriptional level.
      However, little is known about the specific pathways through which miRNAs with
      specific sequence or structural motifs regulate the cellular processes. In this
      paper we showed the broad and deep characteristics of mature miRNAs according to
      their sequence and structural motifs. We investigated a distinct group of miRNAs
      characterized by the presence of specific sequence motifs, such as UGUGU, GU
      repeats and purine/pyrimidine contents. Using computational function and pathway
      analysis of their targeted genes, we were able to observe the relevance of
      sequence and the type of targeted mRNAs. As the consequence of the sequence
      analysis we finally provide the comprehensive description of pathways, biological
      processes and proteins associated with the distinct group of characterized
      miRNAs. Here, we found that the specific group of miRNAs with UGUGU can activate
      the targets associated to the interferon induction pathway or pathways
      prominently observed during carcinogenesis. GU-rich miRNAs are prone to regulate
      mostly processes in neurogenesis, whereas purine/pyrimidine rich miRNAs could be
      involved rather in transport and/or degradation of RNAs. Additionally, we have
      also analyzed the simple sequence repeats (SSRs). Their variation within mature
      miRNAs might be critical for normal miRNA regular activity. Expansion or
      contraction of SSRs in mature miRNA might directly affect its mRNA interaction or
      even change the function of that distinct miRNA. Our results prove that due to
      the specific sequence features, these molecules can also be involved in well
      defined cellular processes depending on their sequence contents. The pathway
      mapping and theoretical gene target identification allowed us to create a
      biological framework to show the relevance of the specific miRNAs in regulation
      the distinct type of targets. 

PMID- 27031952
TI  - Reactive Oxygen Species Play a Role in the Infection of the Necrotrophic Fungi,
      Rhizoctonia solani in Wheat.
AB  - Rhizoctonia solani is a nectrotrophic fungal pathogen that causes billions of
      dollars of damage to agriculture worldwide and infects a broad host range
      including wheat, rice, potato and legumes. In this study we identify wheat genes
      that are differentially expressed in response to the R. solani isolate, AG8,
      using microarray technology. A significant number of wheat genes identified in
      this screen were involved in reactive oxygen species (ROS) production and redox
      regulation. Levels of ROS species were increased in wheat root tissue following
      R. solani infection as determined by Nitro Blue Tetrazolium (NBT), 3,3'
      diaminobenzidine (DAB) and titanium sulphate measurements. Pathogen/ROS related
      genes from R. solani were also tested for expression patterns upon wheat
      infection. TmpL, a R. solani gene homologous to a gene associated with ROS
      regulation in Alternaria brassicicola, and OAH, a R. solani gene homologous to
      oxaloacetate acetylhydrolase which has been shown to produce oxalic acid in
      Sclerotinia sclerotiorum, were highly induced in R. solani when infecting wheat.
      We speculate that the interplay between the wheat and R. solani ROS generating
      proteins may be important for determining the outcome of the wheat/R. solani
      interaction. 

PMID- 27031953
TI  - Evaluation of the Bladder Stimulation Technique to Collect Midstream Urine in
      Infants in a Pediatric Emergency Department.
AB  - OBJECTIVE: Midstream clean-catch urine is an accepted method to diagnose urinary
      tract infection but is impracticable in infants before potty training. We tested
      the bladder stimulation technique to obtain a clean-catch urine sample in
      infants. MATERIALS AND METHODS: We included 142 infants under walking age who
      required a urine sample in a cross-sectional study carried out during a 3-months
      period, from September to November 2014, in the emergency department of the
      University Children's Hospital of Nice (France). A technique based on bladder
      stimulation and lumbar stimulation maneuvers, with at least two attempts, was
      tested by four trained physicians. The success rate and time to obtain urine
      sample within 3 minutes were evaluated. Discomfort (EVENDOL score >=4/15) was
      measured. We estimated the risk factors in the failure of the technique. Chi
      square test or Fisher's exact test were used to compare frequencies. T-test and
      Wilcoxon test were used to compare quantitative data according to the normality
      of the distribution. Risk factors for failure of the technique were evaluated
      using a multivariate logistic regression model. RESULTS: We obtained midstream
      clean-catch urine in 55.6% of infants with a median time of 52.0 s (10.0; 110.0).
      The success rate decreased with age from 88.9% (newborn) to 28.6% (>1 y) (p =
      0.0001) and with weight, from 85.7% (<4 kg) to 28.6% (>10 kg) (p = 0.0004). The
      success rate was 60.8% for infants without discomfort (p<0.0001). Heavy weight
      and discomfort were associated with failure, with adjusted ORs of 1.47 [1.04
      2.31] and 6.65 [2.85-15.54], respectively. CONCLUSION: Bladder stimulation seems
      to be efficient in obtaining midstream urine with a moderate success rate in our
      study sample. This could be an alternative technique for infants before potty
      training but further randomized multicenter studies are needed to validate this
      procedure.

PMID- 27031955
TI  - Determinants of per diem Hospital Costs in Mental Health.
AB  - INTRODUCTION: An understanding of differences in hospital costs between patient
      groups is relevant for the efficient organisation of inpatient care. The main aim
      of this study was to confirm the hypothesis that eight a priori identified cost
      drivers influence per diem hospital costs. A second aim was to explore further
      variables that might influence hospital costs. METHODS: The study included 667
      inpatient episodes consecutively discharged in 2014 at the psychiatric hospital
      of the Medical Centre-University of Freiburg. Fifty-one patient characteristics
      were analysed. Per diem costs were calculated from the hospital perspective based
      on a detailed documentation of resource use. Mixed-effects maximum likelihood
      regression and an ensemble of conditional inference trees were used to analyse
      data. RESULTS: The study confirmed the a priori hypothesis that not being of
      middle age (33-64 years), danger to self, involuntary admission, problems in the
      activities of daily living, the presence of delusional symptoms, the presence of
      affective symptoms, short length of stay and the discharging ward affect per diem
      hospital costs. A patient classification system for prospective per diem payment
      was suggested with the highest per diem hospital costs in episodes having both
      delusional symptoms and involuntary admissions and the lowest hospital costs in
      episodes having neither delusional symptoms nor somatic comorbidities.
      CONCLUSION: Although reliable cost drivers were identified, idiosyncrasies of
      mental health care complicated the identification of clear and consistent
      differences in hospital costs between patient groups. Further research could
      greatly inform current discussions about inpatient mental health reimbursement,
      in particular with multicentre studies that might find algorithms to split
      patients in more resource-homogeneous groups.

PMID- 27031954
TI  - Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term
      Cognitive Impairment in a Model of Experimental Cerebral Malaria.
AB  - Plasmodium falciparum infection causes a wide spectrum of diseases, including
      cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is
      thought to contribute to cerebral malaria pathogenesis. The vasoactive compound
      endothelin-1, a key participant in many inflammatory processes, likely mediates
      vascular and cognitive dysfunctions in cerebral malaria. We previously
      demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal
      experimental cerebral malaria model, sustained memory loss. Herein, we
      demonstrate that an endothelin type A receptor (ETA) antagonist prevented
      experimental cerebral malaria-induced neurocognitive impairments and improved
      survival. ETA antagonism prevented blood-brain barrier disruption and cerebral
      vasoconstriction during experimental cerebral malaria, and reduced brain
      endothelial activation, diminishing brain microvascular congestion. Furthermore,
      exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model
      generally regarded as a non-cerebral malaria negative control for P. berghei ANKA
      infection, led to experimental cerebral malaria-like memory deficits. Our data
      indicate that endothelin-1 is critical in the development of cerebrovascular and
      cognitive impairments with experimental cerebral malaria. This vasoactive peptide
      may thus serve as a potential target for adjunctive therapy in the management of
      cerebral malaria. 

PMID- 27031956
TI  - Dynamics of Scroll Wave in a Three-Dimensional System with Changing Gradient.
AB  - The dynamics of a scroll wave in an excitable medium with gradient excitability
      is studied in detail. Three parameter regimes can be distinguished by the degree
      of gradient. For a small gradient, the system reaches a simple rotating
      synchronization. In this regime, the rigid rotating velocity of spiral waves is
      maximal in the layers with the highest filament twist. As the excitability
      gradient increases, the scroll wave evolutes into a meandering synchronous state.
      This transition is accompanied by a variation in twisting rate. Filament twisting
      may prevent the breakup of spiral waves in the bottom layers with a low
      excitability with which a spiral breaks in a 2D medium. When the gradient is
      large enough, the twisted filament breaks up, which results in a semi-turbulent
      state where the lower part is turbulent while the upper part contains a scroll
      wave with a low twisting filament. 

PMID- 27031957
TI  - Paravascular pathways contribute to vasculitis and neuroinflammation after
      subarachnoid hemorrhage independently of glymphatic control.
AB  - Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The
      mechanisms underlying its pathological complications have not been fully
      identified. Here, we investigate the potential involvement of the glymphatic
      system in the neuropathology of SAH. We demonstrate that blood components rapidly
      enter the paravascular space following SAH and penetrate into the perivascular
      parenchyma throughout the brain, causing disastrous events such as cerebral
      vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread
      perivascular neuroinflammation. Clearance of the paravascular pathway with tissue
      type plasminogen activator ameliorates the behavioral deficits and alleviates
      histological injury of SAH. Interestingly, AQP4(-/-) mice showed no improvements
      in neurological deficits and neuroinflammation at day 7 after SAH compared with
      WT control mice. In conclusion, our study proves that the paravascular pathway
      dynamically mediates the pathological complications following acute SAH
      independently of glymphatic control. 

PMID- 27031958
TI  - Nupr1/Chop signal axis is involved in mitochondrion-related endothelial cell
      apoptosis induced by methamphetamine.
AB  - Methamphetamine (METH) abuse has been a serious global public health problem for
      decades. Previous studies have shown that METH causes detrimental effects on the
      nervous and cardiovascular systems. METH-induced cardiovascular toxicity has
      been, in part, attributed to its destructive effect on vascular endothelial
      cells. However, the underlying mechanism of METH-caused endothelium disruption
      has not been investigated systematically. In this study, we identified a novel
      pathway involved in endothelial cell apoptosis induced by METH. We demonstrated
      that exposure to METH caused mitochondrial apoptosis in human umbilical vein
      endothelial cells and rat cardiac microvascular endothelial cells in vitro as
      well as in rat cardiac endothelial cells in vivo. We found that METH mediated
      endothelial cell apoptosis through Nupr1-Chop/P53-PUMA/Beclin1 signaling pathway.
      Specifically, METH exposure increased the expression of Nupr1, Chop, P53 and
      PUMA. Elevated p53 expression raised up PUMA expression, which initiated
      mitochondrial apoptosis by downregulating antiapoptotic Bcl-2, followed by
      upregulation of proapoptotic Bax, resulting in translocation of cytochrome c
      (cyto c), an apoptogenic factor, from the mitochondria to cytoplasm and
      activation of caspase-dependent pathways. Interestingly, increased Beclin1,
      upregulated by Chop, formed a ternary complex with Bcl-2, thereby decreasing the
      dissociative Bcl-2. As a result, the ratio of dissociative Bcl-2 to Bax was also
      significantly decreased, which led to translocation of cyto c and initiated more
      drastic apoptosis. These findings were supported by data showing METH-induced
      apoptosis was significantly inhibited by silencing Nupr1, Chop or P53, or by PUMA
      or Beclin1 knockdown. Based on the present data, a novel mechanistic model of
      METH-induced endothelial cell toxicity is proposed. Collectively, these results
      highlight that the Nupr1-Chop/P53-PUMA/Beclin1 pathway is essential for
      mitochondrion-related METH-induced endothelial cell apoptosis and may be a
      potential therapeutic target for METH-caused cardiovascular toxicity. Future
      studies using knockout animal models are warranted to substantiate the present
      findings. 

PMID- 27031959
TI  - Dihydroartemisinin attenuates lipopolysaccharide-induced osteoclastogenesis and
      bone loss via the mitochondria-dependent apoptosis pathway.
AB  - Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the
      plant Artemisia annua. Recent studies suggested that DHA has antitumor effects
      utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported
      that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC)
      differentiation, fusion and bone-resorption activity in vitro. Intracellular ROS
      detection revealed that DHA could remarkably increase ROS accumulation during LPS
      induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA
      treatment. We found that DHA-activated caspase-3 increased Bax/Bcl-2 ratio during
      LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic
      inducing factor (AIF) and the release of cytochrome c from the mitochondria into
      the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction
      is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. In
      vivo study showed that DHA treatment decreased OC number, prevents bone loss,
      rescues bone microarchitecture and restores bone strength in LPS-induced bone
      loss mouse model. Together, our findings indicate that DHA is protective against
      LPS-induced bone loss through apoptosis induction of osteoclasts via ROS
      accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may
      be considered as a new therapeutic candidate for treating inflammatory bone loss.

PMID- 27031960
TI  - Renal cell carcinoma escapes death by p53 depletion through transglutaminase 2
      chaperoned autophagy.
AB  - In renal cell carcinoma, transglutaminase 2 (TGase 2) crosslinks p53 in
      autophagosomes, resulting in p53 depletion and the tumor's evasion of apoptosis.
      Inhibition of TGase 2 stabilizes p53 and induces tumor cells to enter apoptosis.
      This study explored the mechanism of TGase 2-dependent p53 degradation. We found
      that TGase 2 competes with human double minute 2 homolog (HDM2) for binding to
      p53; promotes autophagy-dependent p53 degradation in renal cell carcinoma (RCC)
      cell lines under starvation; and binds to p53 and p62 simultaneously without
      ubiquitin-dependent recognition of p62. The bound complex does not have
      crosslinking activity. A binding assay using a series of deletion mutants of p62,
      p53 and TGase 2 revealed that the PB1 (Phox and Bem1p-1) domain of p62 (residues
      85-110) directly interacts with the beta-barrel domains of TGase 2 (residues 592
      687), whereas the HDM2-binding domain (transactivation domain, residues 15-26) of
      p53 interacts with the N terminus of TGase 2 (residues 1-139). In addition to the
      increase in p53 stability due to TGase 2 inhibition, the administration of a DNA
      damaging anti-cancer drug such as doxorubicin-induced apoptosis in RCC cell lines
      and synergistically reduced tumor volume in a xenograft model. Combination
      therapy with a TGase 2 inhibitor and a DNA-damaging agent may represent an
      effective therapeutic approach for treating RCC. 

PMID- 27031961
TI  - Longitudinal characterization of dysfunctional T cell-activation during human
      acute Ebola infection.
AB  - Data on immune responses during human Ebola virus disease (EVD) are scanty, due
      to limitations imposed by biosafety requirements and logistics. A sustained
      activation of T-cells was recently described but functional studies during the
      acute phase of human EVD are still missing. Aim of this work was to evaluate the
      kinetics and functionality of T-cell subsets, as well as the expression of
      activation, autophagy, apoptosis and exhaustion markers during the acute phase of
      EVD until recovery. Two EVD patients admitted to the Italian National Institute
      for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon
      after symptom onset until recovery and analyzed by flow cytometry and ELISpot
      assay. An early and sustained decrease of CD4 T-cells was seen in both patients,
      with an inversion of the CD4/CD8 ratio that was reverted during the recovery
      period. In parallel with the CD4 T-cell depletion, a massive T-cell activation
      occurred and was associated with autophagic/apoptotic phenotype, enhanced
      expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The
      immunological impairment was accompanied by EBV reactivation. The association of
      an early and sustained dysfunctional T-cell activation in parallel to an overall
      CD4 T-cell decline may represent a previously unknown critical point of Ebola
      virus (EBOV)-induced immune subversion. The recent observation of late occurrence
      of EBOV-associated neurological disease highlights the importance to monitor the
      immuno-competence recovery at discharge as a tool to evaluate the risk of late
      sequelae associated with resumption of EBOV replication. Further studies are
      required to define the molecular mechanisms of EVD-driven activation/exhaustion
      and depletion of T-cells. 

PMID- 27031962
TI  - Preventing cell death with a 'check valve' in mitochondrial complex I?

PMID- 27031963
TI  - Parp mutations protect against mitochondrial dysfunction and neurodegeneration in
      a PARKIN model of Parkinson's disease.
AB  - The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is an essential co
      factor for cellular energy generation in mitochondria as well as for DNA repair
      mechanisms in the cell nucleus involving NAD(+)-consuming poly (ADP-ribose)
      polymerases (PARPs). Mitochondrial function is compromised in animal models of
      Parkinson's disease (PD) associated with PARKIN mutations. Here, we uncovered
      alterations in NAD(+) salvage metabolism in Drosophila parkin mutants. We show
      that a dietary supplementation with the NAD(+) precursor nicotinamide rescues
      mitochondrial function and is neuroprotective. Further, by mutating Parp in
      parkin mutants, we show that this increases levels of NAD(+) and its salvage
      metabolites. This also rescues mitochondrial function and suppresses dopaminergic
      neurodegeneration. We conclude that strategies to enhance NAD(+) levels by
      administration of dietary precursors or the inhibition of NAD(+)-dependent
      enzymes, such as PARP, that compete with mitochondria for NAD(+) could be used to
      delay neuronal death associated with mitochondrial dysfunction. 

PMID- 27031964
TI  - Local proliferation initiates macrophage accumulation in adipose tissue during
      obesity.
AB  - Obesity-associated chronic inflammation is characterized by an accumulation of
      adipose tissue macrophages (ATMs). It is generally believed that those
      macrophages are derived from peripheral blood monocytes. However, recent studies
      suggest that local proliferation of macrophages is responsible for ATM
      accumulation. In the present study, we revealed that both migration and
      proliferation contribute to ATM accumulation during obesity development. We show
      that there is a significant increase in ATMs at the early stage of obesity, which
      is largely due to an enhanced in situ macrophage proliferation. This result was
      obtained by employing fat-shielded irradiation and bone marrow reconstitution.
      Additionally, the production of CCL2, a pivotal chemoattractant of monocytes, was
      not found to be increased at this stage, corroborating with a critical role of
      proliferation. Nonetheless, as obesity proceeds, the role of monocyte migration
      into adipose tissue becomes more significant and those new immigrants further
      proliferate locally. These proliferating ATMs mainly reside in crown-like
      structures formed by macrophages surrounding dead adipocytes. We further showed
      that IL-4/STAT6 is a driving force for ATM proliferation. Therefore, we
      demonstrated that local proliferation of resident macrophages contributes to ATM
      accumulation during obesity development and has a key role in obesity-associated
      inflammation. 

PMID- 27031965
TI  - The fine tuning of metabolism, autophagy and differentiation during in vitro
      myogenesis.
AB  - Although the mechanisms controlling skeletal muscle homeostasis have been
      identified, there is a lack of knowledge of the integrated dynamic processes
      occurring during myogenesis and their regulation. Here, metabolism, autophagy and
      differentiation were concomitantly analyzed in mouse muscle satellite cell (MSC)
      derived myoblasts and their cross-talk addressed by drug and genetic
      manipulation. We show that increased mitochondrial biogenesis and activation of
      mammalian target of rapamycin complex 1 inactivation-independent basal autophagy
      characterize the conversion of myoblasts into myotubes. Notably, inhibition of
      autophagic flux halts cell fusion in the latest stages of differentiation and,
      conversely, when the fusion step of myocytes is impaired the biogenesis of
      autophagosomes is also impaired. By using myoblasts derived from p53 null mice,
      we show that in the absence of p53 glycolysis prevails and mitochondrial
      biogenesis is strongly impaired. P53 null myoblasts show defective terminal
      differentiation and attenuated basal autophagy when switched into differentiating
      culture conditions. In conclusion, we demonstrate that basal autophagy
      contributes to a correct execution of myogenesis and that physiological p53
      activity is required for muscle homeostasis by regulating metabolism and by
      affecting autophagy and differentiation. 

PMID- 27031967
TI  - Cathepsin B pulls the emergency brake on cellular necrosis.

PMID- 27031966
TI  - Pdcd4 restrains the self-renewal and white-to-beige transdifferentiation of
      adipose-derived stem cells.
AB  - The stemness maintenance of adipose-derived stem cells (ADSCs) is important for
      adipose homeostasis and energy balance. Programmed cell death 4 (Pdcd4) has been
      demonstrated to be involved in the development of obesity, but its possible roles
      in ADSC function and adipogenic capacity remain unclear. In this study, we
      demonstrate that Pdcd4 is a key controller that limits the self-renewal and white
      to-beige transdifferentiation of ADSCs. Pdcd4 deficiency in mice caused stemness
      enhancement of ADSCs as evidenced by increased expression of CD105, CD90, Nanog
      and Oct4 on ADSCs, together with enhanced in situ proliferation in adipose
      tissues. Pdcd4 deficiency promoted proliferation, colony formation of ADSCs and
      drove more ADSCs entering the S phase accompanied by AKT activation and cyclinD1
      upregulation. Blockade of AKT signaling in Pdcd4-deficient ADSCs led to a marked
      decline in cyclinD1, S-phase entry and cell proliferation, revealing AKT as a
      target for repressing ADSC self-renewal by Pdcd4. Intriguingly, depletion of
      Pdcd4 promoted the transdifferentiation of ADSCs into beige adipocytes. A
      reduction in lipid contents and expression levels of white adipocyte markers
      including C/EBPalpha, PPAR-gamma, adiponectin and alphaP2 was detected in Pdcd4
      deficient ADSCs during white adipogenic differentiation, substituted by typical
      beige adipocyte characteristics including small, multilocular lipid droplets and
      UCP1 expression. More lactate produced by Pdcd4-deficient ADSCs might be an
      important contributor to the expression of UCP1 and white-to-beige
      transdifferentiation. In addition, an elevation of UCP1 expression was confirmed
      in white adipose tissues from Pdcd4-deficient mice upon high-fat diet, which
      displayed increased energy expenditure and resistance to obesity as compared with
      wild-type obese mice. These findings provide evidences that Pdcd4 produces
      unfavorable influences on ADSC stemness, which contribute to adipose dysfunction,
      obesity and metabolic syndromes, thereby proposing Pdcd4 as a potential
      intervening target for regulating ADSC function. 

PMID- 27031968
TI  - Mitochondrial DNA as an initiator of tumorigenesis.

PMID- 27031969
TI  - alphaTAT1: a potential therapeutic target in cancer?

PMID- 27031971
TI  - Health benefits of Ceylon cinnamon (Cinnamomum zeylanicum): a summary of the
      current evidence.

PMID- 27031972
TI  - A study on silicosis among employees of a silica processing factory in the
      Central Province of Sri Lanka.
AB  - OBJECTIVES: The silica industry is rapidly expanding in Sri Lanka. The main
      objective of this study was to assess the prevalence of silicosis among workers
      exposed to silica dust, and to describe the disease pattern of the affected. We
      also screened the affected workers for tuberculosis. METHODS: Employees of a
      silica factory (n=250) were screened using a questionnaire. Details of duration
      of silica exposure and work category within the industry were recorded. All
      symptomatic workers were investigated with chest radiography and screened for
      tuberculosis. International Labour Organisation criteria for diagnosis of
      silicosis were used for diagnosis. RESULTS: Of the 250 employees 25 (10%) had
      respiratory symptoms. Chest radiographs of 14 workers (5.6%) showed abnormalities
      diagnostic of silicosis. The mean age of the affected workers was 29 years. One
      worker had radiological changes suggestive of progressive massive fibrosis. Of 14
      patients, 13 had duration of exposure less than 10 years suggestive of
      accelerated silicosis. Among the 14 workers diagnosed with silicosis five (35.7%)
      had Mantoux induration of more than 10 mm suggestive of latent tuberculesis.
      CONCLUSIONS: Silica workers at the investigated industrial facility are at a
      significant risk of developing accelerated silicosis. Prevalence of infection
      with mycobacteria was high. Education of workers, improvement of protective
      measures and regular monitoring of the work environment should be undertaken to
      avert this deadly disease.

PMID- 27031970
TI  - Long non-coding RNA C2dat1 regulates CaMKIIdelta expression to promote neuronal
      survival through the NF-kappaB signaling pathway following cerebral ischemia.
AB  - Increasing evidence has demonstrated a significant role of long non-coding RNAs
      (lncRNAs) in diverse biological processes. However, their functions in cerebral
      ischemia remain largely unknown. Through an lncRNA array analysis in a rat model
      of focal cerebral ischemia/reperfusion (I/R), we have identified CAMK2D
      associated transcript 1 (C2dat1) as a novel I/R-induced lncRNA that regulated the
      expression of CaMKIIdelta in murine models of focal cerebral ischemia. C2dat1
      mRNA was upregulated in a time-dependent manner in mouse cortical penumbra after
      focal ischemic brain injury, which was accompanied by increased expression of
      CaMKIIdelta at transcript and protein levels. The expression patterns of C2dat1
      and CAMK2D were confirmed in mouse Neuro-2a cells in response to in vitro
      ischemia (oxygen-glucose deprivation/reoxygenation, OGD/R). Knockdown of C2dat1
      resulted in a significant blockade of CaMKIIdelta expression, and potentiated
      OGD/R-induced cell death. Mechanistically, reduced CaMKIIdelta expression upon
      silencing C2dat1 inhibited OGD/R-induced activation of the NF-kappaB signaling
      pathway. Further analysis showed that the downregulation of IKKalpha and IKKbeta
      expression and phosphorylation, and subsequent inhibition of IkappaBalpha
      degradation accounted for the inhibition of the NF-kappaB signaling activity
      caused by silencing C2dat1. In summary, we discovered a novel I/R-induced lncRNA
      C2dat1 that modulates the expression of CaMKIIdelta to impact neuronal survival,
      and may be a potential target for therapeutic intervention of ischemic brain
      injury. 

PMID- 27031973
TI  - Risk estimates of cardiovascular diseases in a Sri Lankan community.
AB  - OBJECTIVES: Quantifying the risk of cardiovascular disease (CVD) in a community
      is important in planning preventive strategies, but such data are limited from
      developing countries, especially South Asia. We aimed to estimate the risks of
      coronary heart disease (CHD), total CVD, and CVD mortality in a Sri Lankan
      community. METHODS: A community survey was conducted in an urban health
      administrative area among individuals aged 35-64 years, selected by stratified
      random sampling. Their 10-year CHD, total CVD, and CVD mortality risks were
      estimated using three risk prediction tools: National Cholesterol Education
      Program-Adult Treatment Panel III (NCEP-ATP III), Systematic Coronary Risk
      Evaluation (SCORE), and World Health Organisation/ International Society of
      Hypertension (WHO/ISH) charts. RESULTS: Among study participants (n=2985), 54.5%
      were females, and mean age (SD) was 52.4 (7.8) years. According to NCEP-ATP III
      ('hard' CHD risk), WHO/ISH (total CVD risk), and SCORE (CVD mortality risk)
      criteria, 25.4% (95% CI 23.6-27.2), 8.2% (95% CI 7.3-9.2), and 11.8 (95% CI 10.5
      13.1) respectively were classified as at 'high risk'. The proportion of high risk
      participants increased with age. 'High risk' was commoner among males (30.3% vs
      20.6%, p<0.001) according to NCEPATP III criteria, but among females (9.7% vs.
      6.7%, p<0.001) according to WHO/ISH criteria. No significant gender difference
      was noted in SCORE risk categories. CONCLUSIONS: A large proportion of
      individuals in this community are at risk of developing cardiovascular diseases,
      especially in older age groups. Risk estimates varied with the different
      prediction tools, and were comparatively higher with NCEP-ATP III charts.

PMID- 27031974
TI  - Growth hormone releasing hormone receptor codon 72 mutation in a cohort of Sri
      Lankan patients with growth hormone deficiency.
AB  - INTRODUCTION: Growth hormone releasing hormone receptor (GHRH-R) codon 72
      mutation is recognised as a common genetic cause of growth hormone deficiency
      (GHD) in the Indian subcontinent resulting in a characteristic lean phenotype.
      Genetic studies have not been previously carried out in Sri Lankans with GHD.
      METHODS: Patients with GHD presenting to a tertiary care referral centre were
      studied for GHRH-R codon 72 mutation by PCR amplification and sequencing. The
      phenotype of the cohort was described as the BMI SDS (Body mass index standard
      deviation score) based on the anthropometric data at the time of diagnosis.
      RESULTS: Among 91 patients from 88 families studied, eight (6 boys) carried the
      codon 72 mutation. The presence of this mutation was low among the Sinhalese
      ethnicity (3 out of 68) than among Tamil and Moor ethnicities. BMI SDS of <-2 was
      seen in 71% of mutation positive and 45.8% of mutation negative patients.
      CONCLUSIONS: Prevalence of GHRH-R codon 72 mutation in this group of GH deficient
      patients was 8.8%. The lean phenotype observed in 71% of the mutation positive
      patients was not a significant association when compared to a similar phenotype
      in 45.8% of the mutation negative patients.

PMID- 27031975
TI  - Validation of the Sinhala version of the Pittsburgh Sleep Quality Index.
AB  - INTRODUCTION: Pittsburg Sleep Quality Index (PSQI) is a widely used standardized
      instrument to assess sleep quality in clinical and research settings. Objective
      of the study was to translate the PSQI into Sinhala language and validate using a
      combined qualitative and quantitative approach. METHODS: Every fifth patient aged
      18-60 years who attended the out-patients department of a tertiary care hospital
      was recruited. PSQI was translated into Sinhala using a combined qualitative and
      quantitative approach. Internal consistency was measured using Cronbach's alpha.
      Construct validity was assessed by comparing the scores in patients who were
      identified as having depressive disorder according to the Centre for
      Epidemiologic Studies Depression Scale (CES-D) and those without depressive
      disorder. RESULTS: Forty-six participants with depression were compared with 159
      non depressed controls. Mean PSQI component scores were significantly higher in
      depressed patients in 5 components. Factor analysis identified a single component
      explaining 53.53% of the variance. Cronbach's alpha of 0.85 indicated a high
      internal consistency. CONCLUSIONS: The Sinhala translation of the PSQI is a valid
      and reliable tool to assess sleep quality.

PMID- 27031976
TI  - Outcome of early coronary intervention for acute ST elevation myocardial
      infarction in a tertiary care cardiac centre in Sri Lanka.
AB  - OBJECTIVES: To describe the outcomes of early percutaneous coronary intervention
      (PCI) for the treatment of acute ST elevation myocardial infarction (STEMI) in a
      tertiary care cardiac centre in Colombo, Sri Lanka. METHODS: Medical records of
      139 consecutive patients presenting to Cardiology Unit 5, National Hospital of
      Sri Lanka from March 2013 to June 2014 with acute STEMI, and treated with early
      PCI as a mode of reperfusion were reviewed. These patients were then followed up
      for 6 months to determine survival, target-vessel revascularization, in-stent
      thrombosis and other major adverse cardiac events (MACE). RESULTS: Of 139
      patients, 116 (83.5%) were male. Mean age was 52.3+/-SD11.1 years. Eighty eight
      (63.3%) patients underwent primary PCI and 51 (36.7%) underwent rescue PCI. There
      were six deaths (4.3%). One occurred on-table and three occurred after discharge.
      Four patients who died had cardiogenic shock. Mean door-to-balloon (DTB) time was
      147 minutes for the primary PCI patients who were transferred from ETU. At six
      months, of 106 patients who attended follow up, two had been re-hospitalised for
      heart failure but none underwent coronary artery bypass grafting (CABG).
      CONCLUSIONS: This report from the national tertiary care cardiology referral
      centre in Sri Lanka, found that the study population was relatively younger,
      similar to other Asian countries. There was high rate of initial success (98.6%)
      and good short-term survival (95.7%), particularly in the subset presenting
      without cardiogenic shock (98.4%) despite the long DTB time. Loss to follow up at
      6 months in this centre was 23.7% (33 patients).

PMID- 27031977
TI  - A sonographic scoring system to assess the risk of thyroid malignancy.
AB  - Prediction of thyroid malignancy with fine needle aspiration cytology or
      individual ultrasound characteristics has several limitations. This study
      evaluates the usefulness of a combination of ultrasound characteristics in
      predicting malignancy in patients with thyroid nodules. We assessed 189 thyroid
      nodules using ultrasonography and histology. Each nodule was assigned a score
      based on ultrasonographic characteristics. This score was compared with histology
      to identify ability to predict malignancy. There were 28 malignant nodules. The
      scoring system was appropriate for clinical use, obtaining an area under ROC
      curve of 0.822 [p< 0.0001] 95% confidence. FNAC of nodules with a score of more
      than 4 can be recommended (100% sensitivity). Nodules with a score less than 8
      can be offered total thyroidectomy when FNAC is inconclusive (97.5% sensitivity).
      A combination of ultrasonographic criteria increase the accuracy of predicting
      malignancy in thyroid nodules. 

PMID- 27031978
TI  - Predicting acute liver failure in dengue infection.
AB  - In a retrospective study involving 240 patients with dengue infection, we
      attempted to identify early predictors of acute liver failure (ALF). Sixteen out
      of 41 patients with serum AST more than 1000 IU/ml developed ALF compared to none
      with serum AST less than 1000 IU/ml. Among patients with serum AST more than 1000
      IU/ml, presence of two of the three following phenomena, within the first 5 days
      of illness: elevated serum bilirubin, elevated alkaline phosphatise or persistent
      nausea and vomiting, predicted development of ALF (93.8% sensitivity, 98.7%
      specificity, 83.3% positive predictive and 99% negative predictive value). The
      presence of elevated serum bilirubin, alkaline phosphatase and persistent nausea
      and vomiting in patients with very high serum AST during the early phase of
      dengue infection should alert the physician of impending ALF. 

PMID- 27031979
TI  - Psychological morbidity and illness perception among patients receiving treatment
      for tuberculosis in a tertiary care centre in Sri Lanka.
AB  - A descriptive cross sectional study was carried out to determine prevalence of
      depression and anxiety and to describe disease perception among patients with
      tuberculosis (TB) at National Hospital for Respiratory Diseases (NHRD), Welisara.
      Consecutive patients on anti-TB therapy admitted to wards and attending clinic
      were recruited until the estimated sample of 430 was reached. They were assessed
      using Hospital Anxiety and Depression Scale (HADS) and Brief Illness Perception
      Questionnaire (BIPQ). A total of 254 in-ward patients and 176 clinic patients
      were included. Of the inward patients, 25.2% had depression and 12.6% had
      anxiety. Of the clinic patients, 17.6% screened were positive for anxiety and
      8.5% screened were positive for depression. Mean BIPQ score was 27.44 for the
      whole population. Prevalence of depression was significantly higher among in-ward
      patients (25.2%, p<0.0001), elderly age groups (20.5%, p=0.007), patients with
      lower education levels (20.6%, p= 0.012) and previously treated patients (32.3%,
      p=0.004). In-ward group (50.8%, p=0.002), lower education group (48.7%,
      p<0.0001), previously treated group (60%, p=0.005) and patients with depression
      (60.8%, p=0.001) and anxiety (68.3%, p<0.0001) showed significanly higher BIPQ
      scores. Our study shows that depression and anxiety are common among patients
      receiving treatment for TB. 

PMID- 27031980
TI  - Thrombotic microangiopathy in a patient with primary dengue fever.

PMID- 27031981
TI  - A case of severe zinc phosphide poisoning.

PMID- 27031982
TI  - Quadriparesis after a wasp sting.

PMID- 27031983
TI  - Reply: Takotsubo cardiomyopathy after an emotional outburst.

PMID- 27031984
TI  - Immune response to hepatitis B vaccination in a group of medical students in Sri
      Lanka.

PMID- 27031985
TI  - Methylovulum psychrotolerans sp. nov., a cold-adapted methanotroph from low
      temperature terrestrial environments, and emended description of the genus
      Methylovulum.
AB  - Two isolates of aerobic methanotrophic bacteria, strains Sph1T and Sph2, were
      obtained from cold methane seeps in a floodplain of the river Mukhrinskaya,
      Irtysh basin, West Siberia. Another morphologically and phenotypically similar
      methanotroph, strain OZ2, was isolated from a sediment of a subarctic freshwater
      lake, Archangelsk region, northern Russia. Cells of these three strains were Gram
      stain-negative, light-pink-pigmented, non-motile, encapsulated, large cocci that
      contained an intracytoplasmic membrane system typical of type I methanotrophs.
      They possessed a particulate methane monooxygenase enzyme and utilized only
      methane and methanol. Strains Sph1T, Sph2 and OZ2 were able to grow at a pH range
      of 4.0-8.9 (optimum at pH 6.0-7.0) and at temperatures between 2 and 36  degrees
      C. Although their temperature optimum was at 20-25  degrees C, these
      methanotrophs grew well at lower temperatures, down to 4  degrees C. The major
      cellular fatty acids were C16 : 1omega5c, C16 : 1omega6c, C16 : 1omega7c, C16 :
      1omega8c, C16 : 0 and C14 : 0; the DNA G+C content was 51.4-51.9 mol%. Strains
      Sph1T, Sph2 and OZ2 displayed nearly identical (99.1-99.7 % similarity) 16S rRNA
      gene sequences and belonged to the family Methylococcaceae of the class
      Gammaproteobacteria. The most closely related organism was Methylovulum
      miyakonense HT12T (96.0-96.5 % 16S rRNA gene sequence similarity and 90 % pmoA
      sequence similarity). The novel isolates, however, differed from Methylovulum
      miyakonense HT12T by cell morphology, pigmentation, absence of soluble methane
      monooxygenase, more active growth at low temperatures, growth over a broader pH
      range and higher DNA G+C content. On the basis of these differences, we propose a
      novel species, Methylovulum psychrotolerans sp. nov., to accommodate these
      methanotrophs. Strain Sph1T (=LMG 29227T=VKM B-3018T) is the type strain. 

PMID- 27031986
TI  - System-Wide Associations between DNA-Methylation, Gene Expression, and Humoral
      Immune Response to Influenza Vaccination.
AB  - Failure to achieve a protected state after influenza vaccination is poorly
      understood but occurs commonly among aged populations experiencing greater
      immunosenescence. In order to better understand immune response in the elderly,
      we studied epigenetic and transcriptomic profiles and humoral immune response
      outcomes in 50-74 year old healthy participants. Associations between DNA
      methylation and gene expression reveal a system-wide regulation of immune
      relevant functions, likely playing a role in regulating a participant's
      propensity to respond to vaccination. Our findings show that sites of methylation
      regulation associated with humoral response to vaccination impact known cellular
      differentiation signaling and antigen presentation pathways. We performed our
      analysis using per-site and regionally average methylation levels, in addition to
      continuous or dichotomized outcome measures. The genes and molecular functions
      implicated by each analysis were compared, highlighting different aspects of the
      biologic mechanisms of immune response affected by differential methylation. Both
      cis-acting (within the gene or promoter) and trans-acting (enhancers and
      transcription factor binding sites) sites show significant associations with
      measures of humoral immunity. Specifically, we identified a group of CpGs that,
      when coordinately hypo-methylated, are associated with lower humoral immune
      response, and methylated with higher response. Additionally, CpGs that
      individually predict humoral immune responses are enriched for polycomb-group and
      FOXP2 transcription factor binding sites. The most robust associations implicate
      differential methylation affecting gene expression levels of genes with known
      roles in immunity (e.g. HLA-B and HLA-DQB2) and immunosenescence. We believe our
      data and analysis strategy highlight new and interesting epigenetic trends
      affecting humoral response to vaccination against influenza; one of the most
      common and impactful viral pathogens. 

PMID- 27031987
TI  - Cardiac Glycosides Activate the Tumor Suppressor and Viral Restriction Factor
      Promyelocytic Leukemia Protein (PML).
AB  - Cardiac glycosides (CGs), inhibitors of Na+/K+-ATPase (NKA), used clinically to
      treat heart failure, have garnered recent attention as potential anti-cancer and
      anti-viral agents. A high-throughput phenotypic screen designed to identify
      modulators of promyelocytic leukemia protein (PML) nuclear body (NB) formation
      revealed the CG gitoxigenin as a potent activator of PML. We demonstrate that
      multiple structurally distinct CGs activate the formation of PML NBs and induce
      PML protein SUMOylation in an NKA-dependent fashion. CG effects on PML occur at
      the post-transcriptional level, mechanistically distinct from previously
      described PML activators and are mediated through signaling events downstream of
      NKA. Curiously, genomic deletion of PML in human cancer cells failed to abrogate
      the cytotoxic effects of CGs and other apoptotic stimuli such as ceramide and
      arsenic trioxide that were previously shown to function through PML in mice.
      These findings suggest that alternative pathways can compensate for PML loss to
      mediate apoptosis in response to CGs and other apoptotic stimuli. 

PMID- 27031988
TI  - Functional analysis of 'a' determinant mutations associated with occult HBV in
      HIV-positive South Africans.
AB  - Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in
      the absence of hepatitis B surface antigen (HBsAg). Occult HBV is associated with
      the development of hepatocellular carcinoma, reactivation during immune
      suppression, and virus transmission. Viral mutations contribute significantly to
      the occult HBV phenotype. Mutations in the 'a' determinant of HBsAg are of
      particular interest, as these mutations are associated with immune escape,
      vaccine escape and diagnostic failure. We examined the effects of selected occult
      HBV-associated mutations identified in a population of HIV-positive South
      Africans on HBsAg production in vitro. Mutations were inserted into two different
      chronic HBV backbones and transfected into a hepatocyte-derived cell line. HBsAg
      levels were quantified by enzyme-linked immunosorbent assay (ELISA), while the
      detectability of mutant HBsAg was determined using an HA-tagged HBsAg expression
      system. Of the seven mutations analysed, four (S132P, C138Y, N146D and C147Y)
      resulted in decreased HBsAg expression in one viral background but not in the
      second viral background. One mutation (N146D) led to a decrease in HBsAg detected
      as compared to HA-tag, indicating that this mutation compromises the ability of
      the ELISA to detect HBsAg. The contribution of occult-associated mutations to the
      HBsAg-negative phenotype of occult HBV cannot be determined adequately by testing
      the effect of the mutation in a single viral background, and rigorous analysis of
      these mutations is required.

PMID- 27031989
TI  - A Lightweight Radio Propagation Model for Vehicular Communication in Road
      Tunnels.
AB  - Radio propagation models (RPMs) are generally employed in Vehicular Ad Hoc
      Networks (VANETs) to predict path loss in multiple operating environments (e.g.
      modern road infrastructure such as flyovers, underpasses and road tunnels). For
      example, different RPMs have been developed to predict propagation behaviour in
      road tunnels. However, most existing RPMs for road tunnels are computationally
      complex and are based on field measurements in frequency band not suitable for
      VANET deployment. Furthermore, in tunnel applications, consequences of moving
      radio obstacles, such as large buses and delivery trucks, are generally not
      considered in existing RPMs. This paper proposes a computationally inexpensive
      RPM with minimal set of parameters to predict path loss in an acceptable range
      for road tunnels. The proposed RPM utilizes geometric properties of the tunnel,
      such as height and width along with the distance between sender and receiver, to
      predict the path loss. The proposed RPM also considers the additional attenuation
      caused by the moving radio obstacles in road tunnels, while requiring a
      negligible overhead in terms of computational complexity. To demonstrate the
      utility of our proposed RPM, we conduct a comparative summary and evaluate its
      performance. Specifically, an extensive data gathering campaign is carried out in
      order to evaluate the proposed RPM. The field measurements use the 5 GHz
      frequency band, which is suitable for vehicular communication. The results
      demonstrate that a close match exists between the predicted values and measured
      values of path loss. In particular, an average accuracy of 94% is found with R2 =
      0.86. 

PMID- 27031990
TI  - Combination of Bioactive Polymeric Membranes and Stem Cells for Periodontal
      Regeneration: In Vitro and In Vivo Analyses.
AB  - Regeneration of periodontal tissues requires a concerted effort to obtain
      consistent and predictable results in vivo. The aim of the present study was to
      test a new family of bioactive polymeric membranes in combination with stem cell
      therapy for periodontal regeneration. In particular, the novel polyester
      poly(isosorbide succinate-co-L-lactide) (PisPLLA) was compared with poly(L
      lactide) (PLLA). Both polymers were combined with collagen (COL), hydroxyapatite
      (HA) and the growth factor bone morphogenetic protein-7 (BMP7), and their
      osteoinductive capacity was evaluated via in vitro and in vivo experiments.
      Membranes composed of PLLA/COL/HA or PisPLLA/COL/HA were able to promote
      periodontal regeneration and new bone formation in fenestration defects in rat
      jaws. According to quantitative real-time polymerase chain reaction (qRT-PCR) and
      Alizarin Red assays, better osteoconductive capacity and increased extracellular
      mineralization were observed for PLLA/COL/HA, whereas better osteoinductive
      properties were associated with PisPLLA/COL/HA. We concluded that membranes
      composed of either PisPLLA/COL/HA or PLLA/COL/HA present promising results in
      vitro as well as in vivo and that these materials could be potentially applied in
      periodontal regeneration. 

PMID- 27031991
TI  - Endothelial Cells Can Regulate Smooth Muscle Cells in Contractile Phenotype
      through the miR-206/ARF6&NCX1/Exosome Axis.
AB  - Active interactions between endothelial cells and smooth muscle cells (SMCs) are
      critical to maintaining the SMC phenotype. Exosomes play an important role in
      intercellular communication. However, little is known about the mechanisms that
      regulate endothelial cells and SMCs crosstalk. We aimed to determine the
      mechanisms underlying the regulation of the SMC phenotype by human umbilical vein
      endothelial cells (HUVECs) through exosomes. We found that HUVECs overexpressing
      miR-206 upregulated contractile marker (alpha-SMA, Smoothelin and Calponin) mRNA
      expression in SMCs. We also found that the expression of miR-206 by HUVECs
      reduced exosome production by regulating ADP-Ribosylation Factor 6 (ARF6) and
      sodium/calcium exchanger 1 (NCX1). Using real-time PCR and western blot analysis,
      we showed that HUVEC-derived exosomes decreased the expression of contractile
      phenotype marker genes (alpha-SMA, Smoothelin and Calponin) in SMCs. Furthermore,
      a reduction of the miR-26a-containing exosomes secreted from HUVECs affects the
      SMC phenotype. We propose a novel mechanism in which miR-206 expression in HUVECs
      maintains the contractile phenotype of SMCs by suppressing exosome secretion from
      HUVECs, particularly miR-26a in exosomes, through targeting ARF6 and NCX1. 

PMID- 27031993
TI  - Stereoselective, Ag-Catalyzed Cyclizations To Access Polysubstituted Pyran Ring
      Systems: Synthesis of C1-C12 Subunit of Madeirolide A.
AB  - The exploration into the scope of a silver-catalyzed cyclization (AgCC) of
      propargyl benzoates for accessing pyran ring systems has been reported. The
      impact of the degree of substitution, nature of the substitution on the carbon
      backbone/benzoate moiety, and stereochemistry has been evaluated. The application
      of this methodology to the synthesis of the C1-C12 southern fragment of
      madeirolide A is disclosed. 

PMID- 27031992
TI  - Endocannabinoid Signaling Regulates Sleep Stability.
AB  - The hypnogenic properties of cannabis have been recognized for centuries, but
      endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly
      characterized. We report findings from a series of experiments in mice measuring
      sleep with polysomnography after various systemic pharmacological manipulations
      of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was
      achieved using an automated algorithm that we devised and validated. Increasing
      endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase
      (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in
      non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM
      bouts (NREM stability). Similarly, direct activation of type 1 cannabinoid (CB1)
      receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184
      had a secondary effect that reduced NREM sleep time and stability. This secondary
      response to these drugs was similar to the early effect of CB1 blockade with the
      antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of
      the effects produced by JZL184 and AM281 were dependent on the time of day this
      drug was administered. While activation of CB1 resulted in only a slight
      reduction in gamma power, CB1 blockade had dramatic effects on broadband power in
      the EEG, particularly at low frequencies. However, CB1 blockade did not
      significantly reduce the rebound in NREM sleep following total sleep deprivation.
      These results support the hypothesis that endocannabinoid signaling through CB1
      is necessary for NREM stability but it is not necessary for sleep homeostasis. 

PMID- 27031994
TI  - Tumor Heterogeneity in Lung Cancer: Assessment with Dynamic Contrast-enhanced MR
      Imaging.
AB  - Purpose To evaluate histogram and texture parameters on pretreatment dynamic
      contrast material-enhanced (DCE) magnetic resonance (MR) images in lung cancer in
      terms of temporal change, optimal time for analysis, and prognostic potential.
      Materials and Methods This retrospective study was approved by the institutional
      review board, and the requirement to obtain informed consent was waived. Thirty
      eight patients with pathologically proved lung cancer undergoing standard
      pretreatment DCE MR imaging were included. A fat-suppressed, T1-weighted, volume
      interpolated breath-hold MR sequence was performed every 30 seconds for 300 and
      480 seconds after contrast material administration. A region of interest was
      manually drawn in the largest cross-sectional area of the tumor on DCE MR images
      to extract semiquantitative perfusion, histogram, and texture parameters.
      Predictability of 2-year progression-free survival (PFS) was analyzed by using
      the Kaplan-Meier method and Cox regression analysis. Results MR histogram and
      texture parameters increased rapidly 30-60 seconds after contrast material
      administration. Standard deviation and entropy then plateaued, whereas skewness
      and kurtosis rapidly decreased. Univariate Cox regression analysis revealed that
      standard deviation and entropy were significant predictors of survival; their
      statistical significance was preserved from 60 to 300 seconds, with the smallest
      P values (P <= .001) occurring from 120 to 180 seconds. At multivariate Cox
      regression analysis, entropy was the sole significant predictor of 2-year PFS
      (hazard ratio at 180 seconds, 10.098 [95% confidence interval: 1.579, 64.577], P
      = .015; hazard ratio at 120 seconds: 11.202 [95% confidence interval: 1.761,
      71.260], P = .010). Conclusion Histogram and texture parameter changes varied
      after contrast material injection. The 120-180-second window after contrast
      material injection was optimal for MR imaging-derived texture parameter and
      entropy at DCE MR imaging. ((c)) RSNA, 2016 Online supplemental material is
      available for this article.

PMID- 27031995
TI  - Targeted Therapy of HER2-Negative Breast Cancer.
AB  - Personalized and targeted treatments are the most discussed topics in oncology.
      However, how much personalized medicine is standard of care nowadays and how much
      is part of our hope for a better future? So far, only a few targeted therapies
      are available in daily practice for the treatment of human epidermal growth
      factor receptor 2 (HER2)-negative breast cancer. And even for these few targeted
      agents - besides those targeting the estrogen receptor (ER) for endocrine
      treatment - thus far, predictive factors are missing. There are many new drugs
      and strategies under evaluation but, unfortunately, they are being developed
      without any cross-comparison. What drug will we choose for which patient in the
      future? Without answering this question oncologists will not be able to
      individualize treatment. Predictive factors for every new splendid drug are
      eagerly needed before it comes to an approval. 

PMID- 27031996
TI  - Occupational Physical Activity and Body Mass Index: Results from the Hispanic
      Community Health Study/Study of Latinos.
AB  - PURPOSE: To examine the associations between overweight/obesity and occupation
      among Hispanics/Latinos, the largest minority population in the U.S. METHODS:
      This study included 7,409 employed individuals in the Hispanic Community Health
      Study/Study of Latinos (HCHS/SOL), a prospective study of Hispanic/Latino
      individuals aged 18-74 in four communities in the U.S. We independently examined
      the relationships between BMI, Occupational Activity (OA), and Total Hours
      Worked, quantified via self-reported hours worked per week and occupation
      assigned Metabolic Equivalents (METs). RESULTS: More than three quarters of the
      participants were either overweight (39.3%) or obese (37.8%). Individuals with a
      primary occupation and those employed in a secondary occupation worked an average
      of 36.8 and 14.6 hrs/wk, respectively. The overall adjusted odds for being obese
      compared to normal weight were 3.2% (AOR = 1.03, 95% CI 1.01, 1.05) and 14.4%
      (AOR = 1.14 95% Cl 1.07, 1.23) greater for each 10 MET*hrs/wk unit of increased
      OA, and each 10-hrs/wk unit of Total Hours Worked, respectively. CONCLUSION: This
      study presents the first findings on the association between OA with
      overweight/obesity among Hispanic/Latino individuals in the U.S. Increasing OA
      and Total Hours Worked per week were independently associated with increasing
      odds of overweight/obesity suggesting that the workplace is only one part of the
      overall energy expenditure dynamic. Our findings point to the need to emphasize
      engaging employed individuals in greater levels of PA outside of the work
      environment to impact overweight/obesity.

PMID- 27031997
TI  - Salivary Anionic Changes after Radiotherapy for Nasopharyngeal Carcinoma: A 1
      Year Prospective Study.
AB  - OBJECTIVES: To investigate the salivary anionic changes of patients with
      nasopharyngeal carcinoma (NPC) treated by radiotherapy. MATERIAL AND METHODS:
      Thirty-eight patients with T1-4, N0-2, M0 NPC received conventional radiotherapy.
      Stimulated whole saliva was collected at baseline and 2, 6 and 12 months after
      radiotherapy. Salivary anions levels were measured using ion chromatography.
      RESULTS: A reduction in stimulated saliva flow and salivary pH was accompanied by
      sustained changes in anionic composition. At 2 months following radiotherapy,
      there was a significant increase in chloride, sulphate, lactate and formate
      levels while significant reductions in nitrate and thiocyanate levels were found.
      No further changes in these anion levels were observed at 6 and 12 months. No
      significant changes were found in phosphate, acetate, or propionate levels
      throughout the study period. CONCLUSIONS: Conventional radiotherapy has a
      significant and prolonged impact on certain anionic species, likely contributing
      to increased cariogenic properties and reduced antimicrobial capacities of saliva
      in NPC patients post-radiotherapy.

PMID- 27031998
TI  - Down-Regulation of TLR and JAK/STAT Pathway Genes Is Associated with Diffuse
      Cutaneous Leishmaniasis: A Gene Expression Analysis in NK Cells from Patients
      Infected with Leishmania mexicana.
AB  - An important NK-cell inhibition with reduced TNF-alpha, IFN-gamma and TLR2
      expression had previously been identified in patients with diffuse cutaneous
      leishmaniasis (DCL) infected with Leishmania mexicana. In an attempt to pinpoint
      alterations in the signaling pathways responsible for the NK-cell dysfunction in
      patients with DCL, this study aimed at identifying differences in the NK-cell
      response towards Leishmania mexicana lipophosphoglycan (LPG) between patients
      with localized and diffuse cutaneous leishmaniasis through gene expression
      profiling. Our results indicate that important genes involved in the innate
      immune response to Leishmania are down-regulated in NK cells from DCL patients,
      particularly TLR and JAK/STAT signaling pathways. This down-regulation showed to
      be independent of LPG stimulation. The study sheds new light for understanding
      the mechanisms that undermine the correct effector functions of NK cells in
      patients with diffuse cutaneous leishmaniasis contributing to a better
      understanding of the pathobiology of leishmaniasis. 

PMID- 27031999
TI  - Peripheral circadian clocks are diversely affected by adrenalectomy.
AB  - Glucocorticoids are considered to synchronize the rhythmicity of clock genes in
      peripheral tissues; however, the role of circadian variations of endogenous
      glucocorticoids is not well defined. In the present study, we examined whether
      peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we
      tested the circadian rhythmicity of core clock genes (Bmal1, Per1-3, Cry1,
      RevErbalpha, Rora), clock-output genes (Dbp, E4bp4) and a glucocorticoid- and
      clock-controlled gene (Gilz) in liver, jejunum, kidney cortex, splenocytes and
      visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock
      gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was
      partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on
      the level of Per1 mRNA in VAT, liver and jejunum, but not in kidney and
      splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of Per2 in
      splenocytes and VAT, Per3 in jejunum, RevErbalpha in VAT and Dbp in VAT, kidney
      and splenocytes, whereas the mRNA amounts of Per1 and Per2 in kidney and Per3 in
      VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had
      minimal effects on Rora and E4bp4 mRNAs. Adrenalectomy also resulted in decreased
      level of Gilz mRNA but did not alter the phase of its diurnal rhythm.
      Collectively, these findings suggest that adrenalectomy alters the mRNA levels of
      core clock genes and clock-output genes in peripheral organs and may cause tissue
      specific modulations of their circadian profiles, which are reflected in changes
      of the amplitudes but not phases. Thus, the circulating corticosteroids are
      necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks
      in a tissue-specific manner.

PMID- 27032002
TI  - Improvement in quality of life among violently injured youth after a brief
      intervention.
AB  - BACKGROUND: Youth directly exposed to violence are at risk for experiencing
      elevated rates of emotional and behavioral problems, revictimization, and
      becoming future perpetrators of violence. Violence intervention and prevention
      programs throughout the country attempt to alleviate some of this burden. To
      date, outcomes have been positive but largely qualitative. Patient-reported
      outcomes offer objective measures to evaluate well-being in youth victimization.
      Our primary aim was to use objective patient-reported quantitative measures to
      assess the change in health-related quality-of-life (HRQOL) scores of youth who
      attended a violence intervention summer camp. This is the first study to evaluate
      such measures in youth victims of violence during an intervention. METHODS: Eight
      to 18-year-old youth who attended a violence intervention summer camp in a
      Midwest urban city over a two-year period participated in a HRQOL survey at
      baseline and at the end of programming (6 weeks). Consented youth used an
      electronic platform to answer validated HRQOL measures. Mean differences in
      scores from baseline to six weeks were calculated and reported. RESULTS: A total
      of 64 youth were recruited and consented to the study. Average change in scores
      improved in most HRQOL domains with the largest change in scores observed in
      school functioning (mean diff, +5.00), emotional functioning (mean diff, +5.26),
      and patient anxiety (mean diff, +3.04). Only participant anger scored worse
      following the intervention (mean diff, -2.26). CONCLUSION: A community-based
      summer program hosting violently injured youth resulted in overall improved
      HRQOL. This was especially significant in the school, anxiety, and emotional
      domains. Future evaluation into the effectiveness of youth programs should
      measure HRQOL to identify at-risk participants and to measure effectiveness.
      LEVEL OF EVIDENCE: Therapeutic/care management study, level III.

PMID- 27032001
TI  - Raman Imaging Spectroscopy as a Tool To Investigate the Cell Damage on
      Aspergillus ochraceus Caused by an Antimicrobial Packaging Containing Benzyl
      Isothiocyanate.
AB  - Raman imaging spectroscopy is a nondestructive analytical method that can be a
      useful tool to obtain detailed information about the molecular composition and
      morphology of biological samples. Its high spatial resolution was used to collect
      spectra of Aspergillus ochraceus, a mold producer of ochratoxin A (OTA), in order
      to investigate the cell damage caused on it by the action of the antimicrobial
      benzyl isothiocyanate (BITC). The study was performed in both direct contact and
      vapor phase, in order to check the use of BITC as active agent in food packaging
      material. The results showed that there were morphologic alteration and a
      characteristic Raman spectrum on spore and hyphae exposed to BITC. BITC was
      accumulated in the mold cells where it caused an enormous amount of alterations
      in cellular components (lipids, proteins, saccharides, amino acids...) and
      cellular functions (cell cycle, respiration, metabolism, transcription of genes,
      fluidity of the cellular wall). All these structural, composition, and metabolic
      changes will affect the production of OTA. Pattern recognition with chemometrics
      using principal component analysis (PCA) demonstrated an excellent separation
      between control and BITC treated samples, both in spores and hyphae. PCA results
      also showed two different affection levels when samples were exposed to BITC in
      the vapor phase.

PMID- 27032000
TI  - Emergence of Klebsiella pneumoniae ST273 Carrying blaNDM-7 and ST656 Carrying
      blaNDM-1 in Manila, Philippines.
AB  - We sought to determine the epidemiology of carbapenem-resistant
      Enterobacteriaceae and to investigate the emergence of carbapenem-resistant
      Klebsiella pneumoniae in two teaching hospitals in Manila, Philippines. We
      screened 364 Enterobacteriaceae for carbapenem resistance between 2012 and 2013
      and detected four carbapenem-resistant K. pneumoniae isolates from three
      different patients. We used whole genome sequencing to determine the antibiotic
      resistance profiles and confirmed the presence of carbapenemase genes by
      multiplex PCR. We used multilocus sequence typing and PCR-based replicon typing
      to genetically characterize the carbapenem-resistant isolates. The carbapenemase
      gene blaNDM was detected in K. pneumoniae isolates from two patients. The first
      patient had ventilator-associated pneumonia and lumbar shunt infection from K.
      pneumoniae ST273 carrying blaNDM-7. The second patient had asymptomatic
      genitourinary colonization with K. pneumoniae ST656 carrying blaNDM-1. The third
      patient had a gluteal abscess with K. pneumoniae ST1 that did not carry a
      carbapenemase gene, but did carry blaDHA-1, blaOXA-1, and blaSHV-1. In this
      study, we report the first cases of blaNDM-carrying pathogens in the Philippines
      and add to the growing evidence of the worldwide spread of ST273 and NDM-7, a
      more efficient carbapenem hydrolyzer than NDM-1.

PMID- 27032003
TI  - Embedding a trauma hospitalist in the trauma service reduces mortality and 30-day
      trauma-related readmissions.
AB  - BACKGROUND: Recognizing the increasing age and comorbid conditions of patients
      admitted to our trauma service, we embedded a hospitalist on the trauma service
      at our Level I trauma center.This program was initiated in January 2013. This
      study was designed to investigate differences in outcomes between trauma patients
      who received care from the trauma hospitalist (THOSP) program and similarly
      medically complex trauma patients who did not receive THOSP care. METHODS: There
      were 566 patients comanaged with THOSP between December 2013 and November 2014.
      These patients were matched (1:2) with propensity scores to a contemporaneous
      control group based on age, Injury Severity Score (ISS), and comorbid conditions.
      Outcomes examined included mortality, trauma-related readmissions, upgrades to
      the intensive care unit, hospital length of stay, the development of in-hospital
      complications, and the frequency of obtaining medical subspecialist consultation.
      Differences in outcomes were compared with Mann-Whitney U-test or chi test as
      appropriate. RESULTS: High-quality matching resulted in the loss of 97 THOSP
      patients for the final analysis. Table 1 shows the balance between the two groups
      after matching. While there was a 1-day increase in hospital length of stay and
      an increase in upgrades to the intensive care unit, there was a reduction in
      mortality, trauma-related readmissions, and the development of renal failure
      after implementation of the THOSP program (Table 2). Implementation of this
      program made no significant difference in the frequency of cardiology,
      nephrology, neurology, or endocrinology consultations. There was also no
      difference in the development of the complications of venous thromboembolism,
      pneumonia, stroke, urinary tract infection, bacteremia, or alcohol withdrawal.
      CONCLUSION: Our study provides evidence that embedding a hospitalist on the
      trauma service reduces mortality and trauma-related readmissions. A reason for
      these improved outcomes may be related to THOSP "vigilance." LEVEL OF EVIDENCE:
      Therapeutic/care management study, level IV.

PMID- 27032004
TI  - The role of laparoscopy in management of stable patients with penetrating
      abdominal trauma and organ evisceration.
AB  - BACKGROUND: Organ evisceration after penetrating abdominal trauma (PAT) carries a
      high rate of significant intra-abdominal injuries. There is uniform agreement
      that organ evisceration warrants immediate laparotomy. Nonoperative management of
      stable asymptomatic patients with evisceration is associated with a high failure
      rate. Most authors exclude patients with organ evisceration from laparoscopic
      management.The aims of this study were to determine the significance of organ
      evisceration in stable patients with PAT and to assess the feasibility of
      laparoscopic management of this group. MATERIALS AND METHODS: Intraoperative
      findings, performed surgery, and complications in stable patients who underwent
      laparoscopy for PAT and evisceration between January 2012 and December 2014 were
      retrospectively analyzed. All unstable patients underwent laparotomy and were
      excluded. RESULTS: A total of 189 stable patients were treated with laparoscopy
      for PAT. Thirty-nine patients (20.6%) had organ evisceration; 37 patients had
      stab wounds and 2 patients had gunshot wounds. Fifteen patients had bowel
      evisceration and 24 had omental evisceration. In total, 25 patients (64%) had
      significant injuries (colon, small bowel, etc.) and required therapeutic
      laparoscopy. The rate of therapeutic laparoscopy was 73% in patients with bowel
      evisceration and 58% in patients with omental evisceration. This difference was
      not statistically significant. The most commonly injured organ was the small
      bowel. The small-bowel repair, resection, and anastomosis were the most commonly
      performed procedures. We did not have any missed injuries. There were neither
      conversions nor significant complications in the postoperative period. Fourteen
      patients avoided nontherapeutic laparotomy. CONCLUSION: Organ evisceration in
      stable patients with PAT is associated with a high rate of significant intra
      abdominal injuries and mandates abdominal exploration. Laparoscopic management is
      feasible, has a high accuracy in identifying intra-abdominal injuries, provides
      all benefits of minimal invasive surgery, and avoids nontherapeutic laparotomy.
      LEVEL OF EVIDENCE: Therapeutic study, level V.

PMID- 27032005
TI  - Improving geriatric trauma outcomes: A small step toward a big problem.
AB  - BACKGROUND: Because of the unique physiology and comorbidities of injured
      geriatric patients, specific interventions are needed to improve outcomes. The
      purpose of this study was to assess the effect of a change in triage criteria for
      injured geriatric patients evaluated at an American College of Surgeons Level I
      trauma center. METHODS: As of October 1, 2013, all injured patients 70 years or
      older were mandated to have the highest-level trauma activation upon emergency
      department (ED) arrival regardless of physiology or mechanism of injury. Patients
      admitted before that date were designated as PRE; those admitted after were
      designated as POST. The study period was from October 1, 2011, through April 30,
      2015. Data collected included demographics, mechanism of injury, hypotension on
      admission, comorbidities, Injury Severity Score (ISS), ED length of stay (LOS),
      complications, and mortality. Bivariate and multivariable analyses were used to
      compare outcomes between the study groups (p < 0.05 was considered significant).
      chi or Fisher's exact test was used as appropriate for bivariate analyses of
      categorical variables; patients' ages were compared using the Wilcoxon rank-sum
      test. RESULTS: A total of 2,269 patients (mean, 80.63 years; mean ISS, 12.2; PRE,
      1,271; POST, 933) were included in the study. On multivariable analysis,
      increasing age, higher ISS, and hypotension were associated with higher
      mortality. POST patients were more likely to have an ED LOS of 2 hours or shorter
      (odds ratio, 1.614; 95% confidence interval, 1.088-2.394) after controlling for
      hypotension, ISS, and comorbidities. POST mortality significantly decreased (odds
      ratio, 0.689; 95% confidence interval, 0.484-0.979). CONCLUSION: Based on age
      alone, the focused intervention of a higher level of trauma activation decreased
      ED LOS and mortality in injured geriatric patients. LEVEL OF EVIDENCE:
      Therapeutic/care management study, level IV.

PMID- 27032006
TI  - The impact of acute coagulopathy on mortality in pediatric trauma patients.
AB  - BACKGROUND: Traumatic coagulopathy (TC) occurs in 24% to 38% of adults and is
      associated with up to a six-fold increase in mortality. This study's purpose was
      to determine the incidence of pediatric TC and its impact on mortality. METHODS:
      A retrospective review (2004-2009) of all trauma patients from our Level I trauma
      center was performed. Coagulopathy was defined as an international normalized
      ratio of 1.5 or higher or activated partial thromboplastin time of more than 36
      seconds or platelets less than 100,000/mm. Clinical outcomes were compared
      between pediatric (younger than 16 years) and adult patients (>=16 years or
      older). RESULTS: A total of 20,126 patients were identified (7.6% pediatric,
      92.4% adult). Mean +/- SD age was 8.7 +/- 4.8 years for pediatric patients and
      37.6 +/- 16.7 years for adults. The incidence of admission coagulopathy was lower
      in children (5.8% vs. 8.4%; p < 0.001). Pediatric patients were less likely to
      develop coagulopathy (8.4% vs. 12.4%; p < 0.001) and developed coagulopathy later
      than adults (102.3 +/- 123.2 hours vs. 59.2 +/- 1,823.9 hours; p < 0.001).
      Traumatic brain injury (TBI) and non-TBI-related coagulopathy increased in
      stepwise fashion with age (up to 19.5% in elderly). Adult and pediatric TC was
      associated with increased mortality (pediatric: 14.4% vs. 0.5%; p = 0.02; adult:
      18.3% vs. 1.8%; p < 0.001). CONCLUSIONS: Pediatric trauma patients are less
      likely to present with coagulopathy, are less likely to develop coagulopathy
      during their admission, and tend to develop coagulopathy later than adults. If
      they develop coagulopathy, however, mortality increases in a stepwise fashion
      with age and is associated with a two- to four-fold increased risk of death.
      LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 27032007
TI  - Derivation and validation of a novel Emergency Surgery Acuity Score (ESAS).
AB  - BACKGROUND: There currently exists no preoperative risk stratification system for
      emergency surgery (ES). We sought to develop an Emergency Surgery Acuity Score
      (ESAS) that helps predict perioperative mortality in ES patients. METHODS: Using
      the 2011 American College of Surgeons' National Surgical Quality Improvement
      Program (ACS-NSQIP) database (derivation cohort), we identified all surgical
      procedures that were classified as "emergent." A three-step methodology was then
      performed. First, multiple logistic regression models were created to identify
      independent predictors (e.g., patient demographics, comorbidities, and
      preoperative laboratory variables) of 30-day mortality in ES. Second, based on
      the relative impact of each identified predictor (i.e., odds ratio), using
      weighted averages, a novel score was derived. Third, using the 2012 ACS-NSQIP
      database (validation cohort), the score was validated by calculating its C
      statistic and evaluating its ability to predict 30-day mortality. RESULTS: From
      280,801 NSQIP cases, 18,439 ES cases were analyzed, of which 1,598 (8.7%)
      resulted in death at 30 days. The multiple logistic regression analyses
      identified 22 independent predictors of mortality. Based on the relative impact
      of these predictors, ESAS was derived with a total score range of 0 to 29. ESAS
      had a C statistic of 0.86; the probability of death at 30 days gradually
      increased from 0% to 36% then 100% at scores of 0, 11, and 22, respectively. In
      the validation phase, 19,552 patients were included, the mortality rate was 7.2%,
      and the ESAS C statistic stayed at 0.86. CONCLUSION: We have therefore developed
      and validated a novel score, ESAS, that accurately predicts mortality in ES
      patients. Such a score could prove useful for (1) preoperative patient
      counseling, (2) identification of patients needing close postoperative
      monitoring, and (3) risk adjustment in any efforts at benchmarking the quality of
      ES. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

PMID- 27032008
TI  - Performance of a regional trauma network: A state-wide analysis.
AB  - BACKGROUND: The Northern Ohio Trauma System (NOTS), established in 2010, is a
      collaborative regional trauma system composed of one level I and several lower
      level trauma centers (TCs) across multiple hospital systems. Mortalities between
      counties in NOTS and other Ohio counties were compared to assess NOTS
      performance. METHODS: State trauma registry was analyzed for patients 15 years or
      older from 2006 to 2012. Mortality change over time was assessed by comparing all
      counties before and after NOTS establishment. Two analyses were done in the post
      NOTS period: (1) a county analysis, comparing Cuyahoga County, the county
      containing NOTS level I TC (L1TC), with other counties containing L1TCs and (2) a
      regional analysis, comparing Cuyahoga and its adjacent counties (i.e., the NOTS
      region) with other L1TC containing regions. The following subgroups were included
      a priori: Injury Severity Score 15 or greater, age 65 years or older, and trauma
      mechanism. RESULTS: A total of 178,143 patients were analyzed. Cuyahoga was the
      only county that had a decrease in mortality for both the overall group and all
      subgroups over time (all p < 0.05). Both the county and regional analyses showed
      that the overall NOTS patients were 1 to 4 years older (p < 0.05), had similar or
      higher Injury Severity Score (p < 0.05), and were treated more often at lower
      level TCs (p < 0.001). County analysis demonstrated that Cuyahoga County had
      approximately 1% lower mortality in geriatrics patients compared with non-NOTS
      counties. Regional analysis showed lower mortality in the NOTS region for the
      overall patient group, as well as geriatric and blunt injuries subgroups.
      CONCLUSIONS: Cuyahoga was the only county in Ohio that had significant mortality
      reduction for all patient groups over time. Trauma system regionalization was
      associated with greater utilization of lower-level TCs and lower patient
      mortality. These findings suggest that a collaborative regional trauma system may
      be more important than the number of L1TC in an area. LEVEL OF EVIDENCE:
      Therapeutic/care management study, level IV.

PMID- 27032010
TI  - Pediatric gunshot wound recidivism: Identification of at-risk youth.
AB  - BACKGROUND: Although penetrating injury is the most common reason for pediatric
      trauma recidivism, there is a paucity of literature specifically looking at this
      population. The objective of this study was to identify those in the pediatric
      community at the highest levels of risk for experiencing gunshot wound (GSW) on
      multiple occasions. METHODS: A retrospective review querying our urban Level I
      trauma database was performed. Patients aged 0 year to 18 years sustaining GSW
      from 2000 to 2011 were selected. This was further refined to include those who
      returned to the hospital for another firearm injury. Demographic data, including
      age of initial and subsequent presentation, sex, race, zip code, home address,
      and disposition were compiled. RESULTS: During the 12-year study period, 896
      pediatric patients were discharged from the hospital after initial firearm injury
      with subsequent 8.8% recidivism rate. All recidivists were male, and 86% were 16
      years to 18 years old at the time of the first injury. The subsequent incident
      occurs within the first year, 2 years, and 3 years 32%, 53%, and 66% of the time,
      respectively. Nine individuals in our study group experienced GSW on three
      separate occasions, with a mortality rate of 22%. Regarding the domicile, 53% of
      the patients were located in a 3-sq mi area containing four public high schools.
      CONCLUSION: Using demographic data, we have been able to identify an at-risk
      population where there is a greater than 1 in 12 chance of getting shot multiple
      times. Use of this type of demographic data can help target those at highest risk
      by allocating resources that can have the greatest impact on this societal
      burden. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 27032011
TI  - Performance improvement and patient safety program-guided quality improvement
      initiatives can significantly reduce computed tomography imaging in pediatric
      trauma patients.
AB  - BACKGROUND: Morbidity and mortality of cervical spine (C-spine) injury in
      pediatric trauma patients are high, necessitating quick and accurate diagnosis.
      Best practices emphasize minimizing radiation exposure through decreased reliance
      on computed tomography (CT), instead using clinical assessment, physical
      examination, and alternate imaging techniques. We implemented an institutional
      performance improvement and patient safety (PIPS) program initiative for C-spine
      clearance in 2010 because of high rates of CT scans among pediatric trauma
      patients. METHODS: A retrospective review of pediatric trauma patients, aged 0
      years to 14 years, in the pre- and post-PIPS implementation periods was
      conducted. Rates of C-spine CT, overall CT, other imaging modalities, radiation
      exposure, patient characteristics, and injury severity were compared, and
      compliance with PIPS protocol was reviewed. RESULTS: Patient characteristics and
      injury severity were similar before and after PIPS implementation. C-spine CT
      rates decreased significantly between groups (30% vs. 13%, p < 0.001), whereas C
      spine plain x-ray rates increased significantly (7% vs. 25%, p < 0.001). There
      was no difference in C-spine magnetic resonance imaging between groups (12% vs.
      10%, p = 0.11). In 2007, 71% of patients received a CT scan for any reason.
      However, the overall CT rate decreased significantly between groups (60% vs. 45%,
      p < 0.001). There was an estimated 22% decrease in lifetime attributable risk
      (LAR) for any cancer due to ionizing imaging exposure in males and 38% decrease
      in females between the pre- and post-PIPS groups. There was a 54% decrease in LAR
      for thyroid cancer in males and females between groups; 2014 compliance with the
      protocol was excellent (82-90% per quarter). CONCLUSIONS: Performance improvement
      and patient safety program-generated protocol can significantly decrease ionizing
      radiation exposure. We demonstrate that a simple protocol focused on C-spine
      imaging has high compliance, decreased C-spine CT scans, and decreased LAR for
      thyroid cancer. A secondary benefit is a reduction in total CT imaging, with an
      associated decrease in LAR for all cancers. LEVEL OF EVIDENCE: Therapeutic study,
      level IV; diagnostic study, level III.

PMID- 27032012
TI  - Early initiation of extracorporeal membrane oxygenation improves survival in
      adult trauma patients with severe adult respiratory distress syndrome.
AB  - BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in the trauma
      population has been reported to have a mortality benefit in patients with severe
      refractory hypoxic respiratory failure. This study compares the early initiation
      of ECMO for the management of severe adult respiratory distress syndrome (ARDS)
      versus a historical control immediately preceding the use of ECMO for trauma
      patients. METHODS: A retrospective study was conducted at a single verified Level
      I trauma center. The study population was limited to trauma patients diagnosed
      with severe ARDS using the Berlin definition (PaO2/FIO2 ratio < 100). Patients
      managed with ECMO versus conventional ventilation (CONV) were compared. The
      primary outcome of interest was mortality; secondary outcomes included hospital
      length of stay, intensive care unit-free days, and ventilator-free days. RESULTS:
      Fifteen ECMO patients managed from March 2013 to November 2014 were identified,
      as were 14 CONV patients managed from March 2012 to February 2013 who met the
      Berlin definition of severe ARDS. Data related to age, Injury Severity Scores
      (ISSs), admission lactic acid levels, base deficit, the number of transfused red
      blood cell units within the first 24 hours, and presence of severe traumatic
      brain injury were collected and were not statistically different between the
      groups. Likewise, Murray Lung Injury (MLI), Sequential Organ Failure Assessment
      (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores
      determined at the onset of severe ARDS were not statistically different between
      the groups. Median hospital stay (CONV, 28.0 days [14.0-47.0]; ECMO, 43.5 days
      [30.0-93.0]; p = 0.15), intensive care unit-free days (CONV, 0.0 days [0.0-5.0];
      ECMO, 5.0 days [0.0-7.0]; p = 0.26), and ventilator-free days (CONV, 0.0 days
      [0.0-10.0]; ECMO, 8.0 days [0.0-19.0]; p = 0.13) were not statistically different
      between the groups. Mortality in the ECMO group was significantly reduced
      compared with the CONV group (ECMO, 13.3%; CONV, 64%; p = 0.01). Timing from the
      onset of severe ARDS to ECMO intervention occurred at a mean 1.9 +/- 1.4 days.
      CONCLUSION: Patients who were treated with ECMO for severe ARDS had an improved
      mortality compared with historical controls. ECMO should be considered at the
      early onset of severe ARDS to improve survival. LEVEL OF EVIDENCE: Therapeutic
      study, level IV.

PMID- 27032013
TI  - The transforming power of early career acute care surgery research scholarships
      on academic productivity.
AB  - BACKGROUND: More than 75% of respondents to an Eastern Association for the
      Surgery of Trauma survey felt that barriers to research had increased and that
      acute care surgeon (ACS) academic productivity had decreased. Recent data confirm
      this impression and show lower academic productivity of junior ACS faculty
      compared with peers in other general surgical fields. The purpose of this study
      was to determine if early career acute care surgery research scholarships are
      associated with improved ACS academic productivity. METHODS: Faculty data at the
      Top 55 National Institutes of Health (NIH)-funded departments of surgery (Top 55)
      were obtained using SCOPUS, NIH, department, and professional society databases.
      Academic productivity was measured using total publications, citations, and the
      Hirsch index. Scholarship recipients from the American Association for the
      Surgery of Trauma and Eastern Association for the Surgery of Trauma were
      identified. RESULTS: A total of 4,101 surgical faculty (8.3% ACS) who belong to
      the Top 55 NIH-funded departments of surgery and 85 scholarship recipients were
      identified. After merging, 34 scholarship recipients (40%) were current faculty
      at a Top 55 NIH-funded department of surgery, and 24 of those (71%) were ACS
      faculty. Scholarship recipients had higher median total publications compared
      with nonrecipients at assistant and associate ranks but not at full professor
      rank. For all ranks, scholarship recipients were more likely to have NIH funding
      compared with nonrecipients (33% vs. 11%, p < 0.05). On multivariable analysis,
      only NIH funding was associated with increased total publications, with an
      average of 89 more publications over a career (p < 0.05). CONCLUSION: Research
      scholarships granted by acute care surgery professional organizations remain
      largely among ACS faculty in Top 55 NIH-funded departments of surgery. Among
      junior ACS faculty, recipients are associated with increased academic
      productivity and NIH funding. To fill the academic productivity gap among junior
      ACSs, professional organizations should consider increasing research funding
      scholarships for promising investigators.

PMID- 27032014
TI  - Are frailty markers associated with serious thoracic and spinal injuries among
      motor vehicle crash occupants?
AB  - BACKGROUND: While age is a known risk factor in trauma, markers of frailty are
      growing in their use in the critically ill. Frailty markers may reflect
      underlying strength and function more than chronologic age, as many modern
      elderly patients are quite active. However, the optimal markers of frailty are
      unknown. METHODS: A retrospective review of The Crash Injury Research and
      Engineering Network (CIREN) database was performed over an 11-year period.
      Computed tomographic images were analyzed for multiple frailty markers, including
      sarcopenia determined by psoas muscle area, osteopenia determined by Hounsfield
      units (HU) of lumbar vertebrae, and vascular disease determined by aortic
      calcification. RESULTS: Overall, 202 patients were included in the review, with a
      mean age of 58.5 years. Median Injury Severity Score was 17. Sarcopenia was
      associated with severe thoracic injury (62.9% vs. 42.5%; p = 0.03). In
      multivariable analysis controlling for crash severity, sarcopenia remained
      associated with severe thoracic injury (p = 0.007) and osteopenia was associated
      with severe spine injury (p = 0.05). While age was not significant in either
      multivariable analysis, the association of sarcopenia and osteopenia with
      development of serious injury was more common with older age. CONCLUSIONS:
      Multiple markers of frailty were associated with severe injury. Frailty may more
      reflect underlying physiology and injury severity than age, although age is
      associated with frailty. LEVEL OF EVIDENCE: Prognostic and epidemiologic study,
      level IV.

PMID- 27032015
TI  - Deprotonated Dicarboxylic Acid Homodimers: Hydrogen Bonds and Atmospheric
      Implications.
AB  - Dicarboxylic acids represent an important class of water-soluble organic
      compounds found in the atmosphere. In this work we are studying properties of
      dicarboxylic acid homodimer complexes (HO2C(CH2)nCO2(-)[HO2C(CH2)nCO2H], n = 0
      12), as potentially important intermediates in aerosol formation processes. Our
      approach is based on experimental data from negative ion photoelectron spectra of
      the dimer complexes combined with updated measurements of the corresponding
      monomer species. These results are analyzed with quantum-mechanical calculations,
      which provide further information about equilibrium structures, thermochemical
      parameters associated with the complex formation, and evaporation rates. We find
      that upon formation of the dimer complexes the electron binding energies increase
      by 1.3-1.7 eV (30.0-39.2 kcal/mol), indicating increased stability of the
      dimerized complexes. Calculations indicate that these dimer complexes are
      characterized by the presence of strong intermolecular hydrogen bonds with high
      binding energies and are thermodynamically favorable to form with low evaporation
      rates. Comparison with the previously studied HSO4(-)[HO2C(CH2)2CO2H] complex (J.
      Phys. Chem. Lett. 2013, 4, 779-785) shows that HO2C(CH2)2CO2(-)[HO2C(CH2)2CO2H]
      has very similar thermochemical properties. These results imply that dicarboxylic
      acids not only can contribute to the heterogeneous complexes formation involving
      sulfuric acid and dicarboxylic acids but also can promote the formation of
      homogeneous complexes by involving dicarboxylic acids themselves. 

PMID- 27032016
TI  - High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and
      Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma.
AB  - Pretreatment plasma D-dimer levels have been reported to predict survival in
      several types of malignancies. The aim of this study was to evaluate the
      prognostic value of D-dimer levels in patients with newly diagnosed natural
      killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival
      was set as 1.2 MUg/mL based on the receiver operating curve analysis. Patients
      with a D-dimer level >= 1.2 MUg/mL had significantly more adverse clinical
      features, including poor performance status, advanced stage diseases, B symptoms,
      elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes,
      more extranodal diseases, and higher International Prognostic Index and natural
      killer/T-cell lymphoma prognostic index scores. A D-dimer level >= 1.2 MUg/mL was
      significantly associated with inferior 3-year overall survival (OS, 13.0 vs.
      68.5%, P < 0.001). In the multivariate analysis, a D-dimer level >= 1.2 MUg/mL
      remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47-6.68, P =
      0.003) after adjusting for other confounding prognostic factors. Among patients
      with Ann Arbor stage I-II diseases, those with a D-dimer level >= 1.2 MUg/mL had
      a significantly worse survival than those with a D-dimer level < 1.2 MUg/mL (3
      year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high
      D-dimer level was similar to that of the advanced-stage patients. In conclusion,
      pretreatment plasma D-dimer level may serve as a simple but effective predictor
      of prognosis in patients with NKTCL. 

PMID- 27032017
TI  - Ten aspects of the Big Five in the Personality Inventory for DSM-5.
AB  - Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) includes a
      dimensional model of personality pathology, operationalized in the Personality
      Inventory for DSM-5 (PID-5), with 25 facets grouped into 5 higher order factors
      resembling the Big Five personality dimensions. The present study tested how well
      these 25 facets could be integrated with the 10-factor structure of traits within
      the Big Five that is operationalized by the Big Five Aspect Scales (BFAS). In 2
      healthy adult samples, 10-factor solutions largely confirmed our hypothesis that
      each of the 10 BFAS would be the highest loading BFAS on 1 and only 1 factor.
      Varying numbers of PID-5 scales were additional markers of each factor, and the
      overall factor structure in the first sample was well replicated in the second.
      Our results allow Cybernetic Big Five Theory (CB5T) to be brought to bear on
      manifestations of personality disorder, because CB5T offers mechanistic
      explanations of the 10 factors measured by the BFAS. Future research, therefore,
      may begin to test hypotheses derived from CB5T regarding the mechanisms that are
      dysfunctional in specific personality disorders.

PMID- 27032018
TI  - Functional Nerve Preservation in Extracranial Head and Neck Schwannoma Surgery.
AB  - IMPORTANCE: A schwannoma is an uncommon, benign neurogenic tumor of Schwann
      cells. Tumor enucleation is the recommended surgical method to preserve function
      of the original nerve, although enucleation does not guarantee completely intact
      nerve function after the operation. OBJECTIVE: To establish a strategy for
      functional preservation in extracranial head and neck schwannoma treatment by
      using an electromyographic (EMG) system during tumor resection. DESIGN, SETTING,
      AND PARTICIPANTS: A retrospective cohort study was conducted of 15 patients who
      underwent surgery for removal of schwannoma tumors between April 1, 2006, and
      March 31, 2015, at an academic tertiary referral center. Data analysis was
      conducted from April 3, 2006, to September 15, 2015. Neurogenic tumors were
      diagnosed according to preoperative findings, and during surgery tumors were
      exposed and given EMG-controlled electrical stimulation to analyze their origins.
      In motor nerve cases, the electrical activity of the muscle was measured and
      recorded by EMG. The tumor was then enucleated by incision along tumor fibers
      mapped using EMG stimulation. If a nerve bundle was visible, we incised along
      there and enucleated the tumor. INTERVENTIONS: A strategy using electrical
      stimulation to improve preservation of nerve function in extracranial head and
      neck schwannoma operations. MAIN OUTCOMES AND MEASURES: Frequency and duration of
      postoperative neurologic complications associated with functional preservation
      surgery with tumor enucleation was evaluated using EMG monitoring according to
      tumor origin. RESULTS: Of the 15 patients with extracranial schwannoma, 9 (60%)
      were women (mean [SD] age, 36.3 [15.3] years). All 15 patients underwent surgery
      using a transcervical approach. The most common nerves of origin were the vagus
      nerve and the sympathetic chain. In sensory or sympathetic nerve cases, the EMG
      response was absent. Two of 5 patients with vagus schwannoma had postoperative
      temporary vocal nerve palsy. These symptoms showed improvement after 1 year.
      There was no tumor recurrence during the follow-up period in any patient.
      CONCLUSIONS AND RELEVANCE: The strategy used here demonstrated a method of
      diagnosis and nerve preservation surgery for extracranial schwannomas. Nerve
      functionality was preserved in all vagus schwannoma cases. However, preservation
      of nerve function in sympathetic nerve schwannoma cases remains problematic and
      needs further investigation.

PMID- 27032019
TI  - Visual Outcomes After Descemet Membrane Endothelial Keratoplasty Versus Descemet
      Stripping Automated Endothelial Keratoplasty-Comparison of Specific Matched
      Pairs.
AB  - PURPOSE: To compare visual rehabilitation after Descemet membrane endothelial
      keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty
      (DSAEK) for Fuchs endothelial dystrophy. METHODS: The medical records of patients
      undergoing endothelial keratoplasty were retrospectively evaluated. A DMEK (n =
      25 eyes) and a DSAEK (n = 25 eyes) group were formed. Specific matched pairs
      consisting of 1 DMEK and 1 DSAEK eye with the same preoperative best spectacle
      corrected visual acuity (BSCVA) were built and compared with regard to visual
      rehabilitation, subjective refraction, central corneal thickness, and endothelial
      cell density. RESULTS: Preoperative median BSCVA (logarithm of the minimal angle
      of resolution) was for both groups 0.7 (range, 0.2-1.70). At 12 months, median
      BSCVA was 0.0 (range, -0.08 to 0.7) after DMEK and 0.3 (range, 0.1-0.52) after
      DSAEK (P < 0.001). The spherical equivalent changed after DMEK from 0.0 D (range,
      -2.75 to 4.63 D) to 0.5 D (range, -1 to 2.5 D) and after DSAEK from -0.32 D
      (range, -2.50 to 1 D) to 0.63 D (range, -2.38 to 2 D). Central corneal thickness
      decreased from 718 MUm (range, 566-1041 MUm) to 533 MUm (range, 460-605 MUm)
      after DMEK and from 650 MUm (range, 527-749 MUm) to 605 MUm (range, 486-650 MUm)
      after DSAEK. Endothelial cell density decreased from 2448 cells/mm (range, 2106
      3000 cells/mm) to 1263 cells/mm (range, 589-2282 cells/mm) after DMEK and from
      2348 cells/mm (range, 2156-2781 cells/mm) to 1327 cells/mm (range, 664-1972
      cells/mm) after DSAEK. CONCLUSIONS: DMEK patients showed faster rehabilitation
      and higher BSCVA at all postoperative visits; however, the decline in graft's
      endothelial cell count and change in the spherical equivalent were similar for
      both procedures.

PMID- 27032020
TI  - In Situ Corneal Cross-Linking for Recurrent Corneal Melting After Boston Type 1
      Keratoprosthesis.
AB  - PURPOSE: To present a new treatment modality for recurrent corneal melting in a
      patient with a Boston type I keratoprosthesis (B-KPro) including in situ corneal
      cross-linking (CXL) and lamellar keratoplasty (LKP) as combined treatment.
      METHODS: Case report. RESULTS: Our report concerns a 27-year-old man whose case
      history involved a severe chemical burn of his left eye. After failed penetrating
      keratoplasty and limbal stem cell transplantation, the patient underwent B-KPro
      implantation. Starting 1 month after surgery, recurrent corneal melting around
      the B-KPro developed, which was eventually treated by combining LKP, amniotic
      membrane transplantation, and in situ CXL. Optical coherence tomography imaging
      and follow-up for 12 months showed stable corneal healing without new melting or
      erosion. The ultraviolet A treatment did not seem to damage the material of the B
      KPro. CONCLUSIONS: In situ CXL using riboflavin and ultraviolet A light combined
      with LKP and amniotic membrane transplantation can be an effective management
      option to treat recurrent corneal melting after B-KPro implantation.

PMID- 27032021
TI  - Effectiveness of Intraductal Meibomian Gland Probing for Obstructive Meibomian
      Gland Dysfunction.
AB  - PURPOSE: To evaluate the short-term effectiveness of intraductal meibomian gland
      probing using modified Maskin cannulas in patients with obstructive meibomian
      gland dysfunction. METHODS: The study prospectively included 58 eyes of 30
      patients with a diagnosis of meibomian gland dysfunction who were refractory to
      medical treatment for at least 6 months. The patients were divided into 4 groups
      according to the number of probing procedures applied. During probing, sterile
      modified Maskin probes 2, 2.5, 4, and 6 mm in length were used. A tarsal massage
      was recommended after medical treatment. Preoperatively, then postoperatively at
      1 week, 1 month, and 3 months, the Schirmer 1 test was performed, tear break-up
      time was measured, and images of the anterior segment were recorded. In addition,
      the Ocular Surface Disease Index questionnaire was completed at baseline and at 3
      months. RESULTS: In all groups, there were no statistically significant
      differences between Schirmer 1 test results at preoperative and postoperative 3
      months, but tear break-up time values measured at baseline and at 3 months
      differed significantly (5 seconds, 13 seconds, P < 0.001). In the analyses of
      anterior segment photographs of all patients, statistically significant
      postprocedural decreases in conjunctival hyperemia (P < 0.0001) and eyelid margin
      vascularization (P = 0.004) were detected, and the later Ocular Surface Disease
      Index scores showed a significant improvement between preop and 3 months.
      CONCLUSIONS: A procedure using modified Maskin probes was effective and reliable
      in the short term for patients with meibomian gland dysfunction.

PMID- 27032022
TI  - Phototherapeutic Keratectomy in Salzmann Nodular Degeneration With "Optical
      Cornea Plana".
AB  - PURPOSE: Typically, we observe an unintended hyperopic shift after
      phototherapeutic keratectomy (PTK). Despite a clear optical axis, elevations of
      the mid-peripheral cornea often lead to remarkable visual impairment in Salzmann
      nodular degeneration (SND). The aim of this study was to analyze the effect of
      mechanical pannus removal and PTK on the corneal curvature in SND. METHODS:
      Fifteen eyes of 10 patients with visual impairment caused by SND were treated
      with combined pannus removal and PTK using a masking fluid. Mean age was 53
      years. We analyzed best-corrected visual acuity, central corneal power (in
      diopters, D), spherical equivalent (in D), and irregularity of corneal topography
      (Index of Surface Variance, Pentacam). RESULTS: Best corrected visual acuity
      before PTK was 0.64 (median) and improved to 0.85 (median) after the surgical
      procedure. Mean spherical equivalent was reduced by 1.82 +/- 1.4 D from +2.53 D
      preoperatively to +0.75 D postoperatively (P = 0.001). Mean central corneal power
      increased by 3.18 +/- 3.5 D from 39.8 +/- 4.6 D preoperatively to 43 +/- 1.7 D
      postoperatively (P = 0.013). Topographic irregularity normalized from 83.9 +/-
      53.7 (27-204) to 33.3 +/- 14.3 (20-56; Index of Surface Variance) (P = 0.016).
      CONCLUSIONS: In SND, asymmetric tear film pooling caused by nodules located in
      the mid-periphery of the cornea may lead to an "optical cornea plana," which
      results in a marked hyperopic shift accompanied with high irregular astigmatism.
      Pannus removal combined with excimer laser PTK may restore visual performance, at
      least in part, because of a myopic shift and regularization of the corneal
      curvature.

PMID- 27032023
TI  - Bilateral Descemet Membrane Endothelial Keratoplasty: Analysis of Clinical
      Outcome in First and Fellow Eye.
AB  - PURPOSE: To analyze the clinical outcomes, complications, comparability, and
      predictors of sequential bilateral Descemet membrane endothelial keratoplasty
      (DMEK). METHODS: Retrospective analyses were completed on 60 patients (120 eyes)
      with corneal endothelial disorders who underwent bilateral sequential DMEK. Main
      outcome measures were best-corrected visual acuity (BCVA), pachymetry,
      endothelial cell density, rebubbling frequency, and graft or nongraft-associated
      complications-as measured 6 and 12 months after surgery. RESULTS: BCVA,
      pachymetry, and endothelial cell loss did not differ significantly 6 and 12
      months after surgery in first versus fellow eyes (P > 0.05, respectively). Graft
      and nongraft-associated complications such as graft detachment, graft failure,
      graft rejection, anterior chamber inflammation, and intraocular pressure
      decompensation did not differ significantly between first and fellow eyes (P >
      0.05, respectively). The BCVA of first eyes 6 and 12 months after surgery
      correlates significantly with the 12-month BCVA of fellow eyes (r = 0.454, P =
      0.031; r = 0.602, P = 0.001, respectively). Nevertheless, it was not possible to
      identify BCVA as an influencing variable on fellow eye outcome in regression
      modeling. Early sequential DMEK did not increase patients' risk of early immune
      reactions in their fellow eyes. CONCLUSIONS: The clinical outcomes of first and
      fellow eyes were comparable in patients after DMEK. This suggests patients will
      experience good fellow eye outcomes after successful first eye DMEK. When certain
      quality characteristics are maintained, donor differences do not significantly
      affect DMEK results. We found no significant correlation in postoperative
      complications in first and fellow eye DMEK surgeries.

PMID- 27032024
TI  - Increased Straylight in Patients With Keratoconjunctivitis Sicca.
AB  - PURPOSE: (1) To qualify complaints of quality of vision in patients with (severe)
      keratoconjunctivitis sicca by examining straylight values and (2) to check for an
      effect of scleral lens wear on straylight. METHODS: Straylight was measured in 16
      patients with severe keratoconjunctivitis sicca using the Oculus C-Quant. In 9 of
      these patients, scleral lenses were used, and straylight was measured with and
      without scleral lenses. Other tests included the Schirmer test, visual acuity,
      the van Bijsterveld score, and a straylight questionnaire. RESULTS: Patients with
      keratoconjunctivitis sicca had a mean straylight OD of log(s) = 1.36 +/- 0.19 SD
      and OS of log(s) = 1.45 +/- 0.17 SD. Mean age was 56 +/- 9.3 SD. This was
      significantly higher than the mean age-matched normal value of log(s) = 1.10 (P <
      0.001). Such a straylight increase is functionally significant. The difference in
      straylight with and without scleral lenses was 0.06 log units +/- 0.02 SD, but
      this was not statistically significant for OD (P = 0.134) and OS (P = 0.293). No
      correlation was found between straylight and the van Bijsterveld score on the
      corneal section for OD (P = 0.326) and OS (P = 0.433). CONCLUSIONS:
      Keratoconjunctivitis sicca leads to increased straylight. However, this increase
      was not correlated to the amount of surface damage graded with the van
      Bijsterveld score. Further study on the cornea is necessary to determine the
      source of the increased straylight. Scleral lenses do not have a noteworthy
      influence on straylight in these patients.

PMID- 27032025
TI  - Identification of Mutations in the PRDM5 Gene in Brittle Cornea Syndrome.
AB  - BACKGROUND: Brittle cornea syndrome (BCS) is a rare autosomal recessive
      connective tissue disease characterized by variable combinations of corneal
      thinning and fragility, corneal ruptures either spontaneously or after minor
      trauma, blue sclerae, keratoconus, keratoglobus, and high myopia. So far,
      mutations in 2 genes, PRDM5 and ZNF469, have been associated with BCS. The
      purpose of this study is to describe novel mutations in the PRDM5 gene in
      patients with BCS. METHODS AND RESULTS: Using homozygosity mapping with single
      nucleotide polymorphism markers followed by whole-exome sequencing, we identified
      a novel homozygous splice site variant (c.93+5G>A) in the PRDM5 gene in a
      consanguineous Pakistani family with 4 affected individuals. Reverse
      transcription-polymerase chain reaction analysis from lymphocyte-derived RNA
      failed to reveal any exon skipping because of this splice site variant. A
      homozygous variant (c.11T>G; p.Gln4Pro) in SEC24D also segregated with the
      disease in this particular family. One previously known mutation (c.974del;
      p.Cys325LeufsX2) was identified in a sporadic patient with BCS from Serbia.
      CONCLUSIONS: The current study revealed a novel mutation in the PRDM5 gene in a
      BCS family and recurrent mutation in a sporadic BCS patient. A variant in the
      SEC24D gene also segregated in the BCS family, although its role in the disease
      remains unclear.

PMID- 27032026
TI  - Investigation of Glutathione S-Transferase Isoenzyme Protein Expression in
      Patients With Pterygium.
AB  - PURPOSE: We investigated glutathione S-transferase (GST) enzymes in terms of
      their potential effects on the pathogenesis of pterygium. METHODS: Twenty-six
      pterygium specimens and 15 normal conjunctival specimens of 15 control subjects
      were investigated. Expressions of GST (alpha, mu, pi, and theta) enzymes were
      assessed by immunohistochemical staining. A brown color in the cytoplasm and/or
      nuclei of epithelial cells was evaluated as positive staining for GST enzymes.
      For each antibody, the intensity of the reaction [negative (-), weak (1+),
      moderate (2+), or strong (3+)] was determined to describe the immunoreactions.
      RESULTS: The median age was 52 years in the both groups. There was no significant
      difference between the groups in terms of age, sex, and intraocular pressure
      measurements (P > 0.05 for all). Of the 26 pterygium specimens, 15 (57.7%) (8
      weak, 4 moderate, and 3 strong staining) were identified with GST pi-1 (GSTP1)
      expression and 20 (76.9%) (12 weak, 7 moderate, and 1 strong staining) with GST
      theta-1 (GSTT1) expression. Of the 15 control specimens, 4 (26.7%) (4 weak
      staining) were identified with the GSTP1 expression, and 1 (6.7%) with GSTT1
      expression. GSTP1 and GSTT1 expressions were significantly higher in the
      pterygium specimens than in the controls (P = 0.043, P < 0.001; respectively).
      None of tissue specimens had positive staining for GST mu-1 or GST alpha-1 in
      both groups (both; P = 1.00). CONCLUSIONS: The significant increase of GSTP1 and
      GSTT1 expressions in pterygium may be because of the increased activation of GST
      in response to excessive free radical formation from ultraviolet exposure to
      maintain antioxidant capacity in pterygium.

PMID- 27032027
TI  - Effects of Humidity on Tests of Tear Production.
AB  - PURPOSE: To determine if the Schirmer test is affected by environmental humidity,
      to quantify any effects, and to consider the ways in which this may affect the
      diagnosis of dry eye disease. METHODS: All experiments took place within a
      controlled environment chamber at a range of 5% to 95% relative humidity (RH). In
      vitro testing immersed Schirmer strips at 5 mm depth in water for 5 minutes. In
      vivo tests were conducted using the standard clinical method. All experiments
      were conducted using both standard Schirmer strips and Schirmer strips sheathed
      in a plastic film in order to reduce the possible effects of evaporation.
      RESULTS: In vitro results showed a clear decrease in Schirmer wetting length as
      RH was reduced. Schirmer test strips that were encased within a plastic sheathing
      were less affected by changing RH. As well as wetting length, the rate of wetting
      of Schirmer strips was also affected by changes in RH. In vivo data showed that
      Schirmer results in participants with severe dry eye disease were less affected
      by changes in RH than "normal" participants. CONCLUSIONS: Patients with severe
      dry eye disease produce Schirmer test results which are unaffected by
      environmental humidity. However, patients with moderate Schirmer wetting lengths
      may be falsely diagnosed as having dry eye disease if their test is undertaken in
      a low-humidity environment. This phenomenon may be overcome with the use of
      plastic sheathing. Previous studies investigating the effects of environmental
      conditions on the tear film may have been affected by this phenomenon.

PMID- 27032028
TI  - Early Deep Anterior Lamellar Keratoplasty (DALK) for Acanthamoeba Keratitis-How
      to Define Early?

PMID- 27032029
TI  - The intestinal microbiota of piglets fed with wheat bran variants as
      characterised by 16S rRNA next-generation amplicon sequencing.
AB  - The intestinal microbiota of piglets fed with a Control diet low in dietary fibre
      and modified wheat bran variants as an additional source of insoluble dietary
      fibre was characterised. In this context, variances in the microbiota of three
      different gut segments were assessed. Wheat bran was either included in its
      native form or modified by fermentation and extrusion before added at 150 g/kg to
      a basal diet for 48 piglets (12 animals per treatment). Total DNA was extracted
      from digesta samples from the jejunum, the end of the ileum and the colon
      ascendens. Samples were prepared accordingly for subsequent sequencing with the
      Illumina MiSeq. The obtained results revealed distinct location-specific
      differences in microbial composition. While Firmicutes were most predominant in
      all three gut segments, Bacteroidetes were additionally found in the colon at
      high abundance. The parameters of alpha and beta diversity analysis showed
      significant differences (p < 0.01) between the colon and the other two gut
      segments. Specialised bacterial groups like Prevotella and Ruminococcaceae were
      among the most predominant ones found in the colon, as they possess cellulolytic
      properties to degrade (at least partially) non-starch polysaccharides, while
      their abundance was negligible in the jejunum and the ileum. Conversely, the
      genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among
      the most predominant groups in the jejunum and ileum, while in the colon they
      were hardly found. Although statistical taxonomical evaluation, following p-value
      correction, did not reveal pronounced differences in abundance related to bran
      modification, alpha and beta diversity analysis showed an influence regarding the
      various feeding strategies applied. Based on these findings, a more in-depth view
      on intestinal microbial composition within the gastrointestinal tract of young
      pigs fed with low- and high-fibre diets was generated. 

PMID- 27032030
TI  - Effects of diets differing in protein source and technical treatment on
      digestibility, performance and visceral and biochemical parameters of fattening
      pigs.
AB  - The aim of the experiment on 100 cross-bred barrows was to compare commercial
      diets for fattening pigs based on either soya bean meal (SBM) imported from non
      European countries with diets based on a mixture of locally produced rape seed
      meal, distillers' dried grains with solubles and soya beans as main protein
      sources. In addition, these both types of diets were processed by two different
      technical feed treatments, i.e. coarse grinding without hydrothermal treatment or
      fine grinding and pelleting. With only few exceptions, nutrients of the diet
      without SBM were more digestible (p < 0.05) resulting in a higher metabolisable
      energy (ME) content. Fine grinding and pelleting increased also the ME content
      and the nutrient digestibility with the exception of crude fibre. Higher feed
      intake of animals that fed diets without SBM (p < 0.01) resulted in higher
      average daily gain (p < 0.01). However feeding this diet, the higher
      digestibility was not reflected in a decreased feed-to-gain ratio (FGR), but fine
      grinding and pelleting reduced FGR (p < 0.001). A higher pH value and a lower DM
      content of caecal chymus were detected in animals that received coarsely ground
      feed (p < 0.05). Animals that fed finely ground and pelleted feed had higher
      slaughter and relative liver weights and higher blood cholesterol concentrations
      (p = 0.040). The urea concentrations of blood were lower (p = 0.019) after
      feeding diets without SBM. In conclusion, SBM imported from non-European
      countries can be replaced by alternative local protein sources without
      compromising digestibility or performances of animals. Although fine grinding and
      thermal treatment particularly seemed to be advantageous for digestibility and
      performance, the possible risk of development of stomach lesions should be
      considered. 

PMID- 27032031
TI  - Effects of dietary addition of cellulase and a Saccharomyces cerevisiae
      fermentation product on nutrient digestibility, rumen fermentation and enteric
      methane emissions in growing goats.
AB  - This study was designed to assess the effectiveness of dietary cellulase (243
      U/g, derived from Neocallimastix patriciarum) and a Saccharomyces cerevisiae
      fermentation product (yeast product) on ruminal fermentation characteristics,
      enteric methane (CH4) emissions and methanogenic community in growing goats. The
      experiment was conducted in a 5 * 5 Latin square design using five Xiangdong
      black wether goats. The treatments included a Control and two levels of cellulase
      (0.8 g and 1.6 g/kg dry matter intake (DMI), i.e. 194 U/kg and 389 U/kg DMI,
      respectively) crossed over with two levels (6 g or 12 g/kg DMI) of the yeast
      product. There were no significant differences regarding feed intake, apparent
      digestibility of organic matter, neutral detergent fibre and acid detergent fibre
      among all the treatments. In comparison with the Control, the ruminal ammonia N
      concentration was decreased (p = 0.001) by cellulase and yeast product addition.
      The activities of carboxymethylcellulase and xylanase were decreased after
      cellulase addition. Moreover, dietary cellulase and yeast product addition led to
      a significant reduction (p < 0.05) of enteric CH4 emissions although the
      diversity and copy numbers of methanogens among treatments were not dissimilar.
      The present results indicate that the combination of cellulase and yeast
      fermentation product can reduce the production of CH4 energy and mitigate the
      enteric CH4 emissions to a certain degree. 

PMID- 27032032
TI  - Effects of starter feeding and early weaning on GHR mRNA expression in liver and
      rumen of lambs from birth to 84 days of age.
AB  - The growth hormone receptor (GHR) is associated with animal growth and
      development. To investigate such effects on GHR gene expression, a total of 102
      Hu lambs were randomly allocated to one of three groups (Group 1: starter diet
      from 7 d of age, weaning at 56 d of age; Group 2: starter diet from 42 d of age,
      weaning at 56 d of age; Group 3: starter diet from 7 d of age; weaning at 28 d of
      age). Six lambs from each group were sacrificed every 14 d to investigate the
      effects of starter feeding and weaning age on GHR mRNA expression in the liver
      and rumen. The results revealed that GHR mRNA expression was significantly higher
      in the liver and rumen (p < 0.05) than in other tissues. Early starter feeding up
      regulated hepatic GHR mRNA expression on days 14, 28, 42 and 56 and ruminal GHR
      mRNA expression on days 28, 42, 70, and 84 (p < 0.05). Early weaning up-regulated
      hepatic GHR mRNA expression on days 56, 70 and 84 and ruminal GHR mRNA expression
      on days 42, 56, 70 and 84 (p < 0.05). Dietary and weaning regimes and age
      affected the hepatic and ruminal GHR mRNA expression. 

PMID- 27032033
TI  - Stretchable Spin Valve with Stable Magnetic Field Sensitivity by Ribbon-Patterned
      Periodic Wrinkles.
AB  - A strain-relief structure by combining the strain-engineered periodic wrinkles
      and the parallel ribbons was employed to fabricate flexible dual spin valves onto
      PDMS substrates in a direct sputtering method. The strain-relief structure can
      accommodate the biaxial strain accompanying with stretching operation (the
      uniaxial applied tensile strain and the induced transverse compressive strain due
      to the Poisson effect), thus significantly reducing the influence of the residual
      strain on the giant magnetoresistance (GMR) performance. The fabricated GMR dual
      spin-valve sensor exhibits the nearly unchanged MR ratio of 9.9%, magnetic field
      sensitivity up to 0.69%/Oe, and zero-field resistance in a wide range of
      stretching strain, making it promising for applications on a conformal shape or a
      movement part.

PMID- 27032034
TI  - Association of Etonogestrel-Releasing Contraceptive Implant with Reduced Weight
      Gain in an Exclusively Breastfed Infant: Report and Literature Review.
AB  - BACKGROUND: Studies have not found that hormonal contraceptive implants adversely
      affect breastfeeding, but theoretical concerns exist. METHODS: We reported a case
      of reduced weight gain in an exclusively breastfed infant in association with
      placement of (ENG)-releasing contraceptive implant (Nexplanon) to the FDA Adverse
      Events Reporting System (FAERS). We further queried reports to FAERS and reviewed
      published studies of the ENG implant during breastfeeding. RESULTS: A
      breastfeeding mother received an ENG implant at 4 weeks postpartum. Her infant
      was exclusively breastfeeding. One month after implant placement, the infant had
      lost 145 g, dropping from the 44th percentile to the 6th percentile for growth.
      During this period, the mother had not returned to work or decreased frequency of
      feeding. During a 2-year period of FAERS reports, we found one other report of
      reduced milk supply following ENG implant placement. Among 108 breastfeeding
      women studied while using the ENG implant, there was one case of lactation
      failure. If this were not due to chance, the estimated risk of lactation failure
      with the ENG implant would be 0.9% (95% confidence interval 0.2-5.1%).
      CONCLUSION: Given uncertainty regarding the true effect of ENG implants on
      lactation, it seems prudent for providers to counsel each woman about a possible
      effect on milk supply so that she can monitor her infant for signs of impaired
      milk transfer. Patient-centered counseling approaches are needed that allow each
      woman to assess her own individual tolerance of risk of unplanned pregnancy
      versus possible risk of lactation failure.

PMID- 27032035
TI  - A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer
      at Initial Biopsy.
AB  - IMPORTANCE: Overdiagnosis and overtreatment of indolent prostate cancer (PCA) is
      a serious health issue in most developed countries. There is an unmet clinical
      need for noninvasive, easy to administer, diagnostic assays to help assess
      whether a prostate biopsy is warranted. OBJECTIVE: To determine the performance
      of a novel urine exosome gene expression assay (the ExoDx Prostate IntelliScore
      urine exosome assay) plus standard of care (SOC) (ie, prostate-specific antigen
      [PSA] level, age, race, and family history) vs SOC alone for discriminating
      between Gleason score (GS)7 and GS6 and benign disease on initial biopsy. DESIGN,
      SETTING, AND PARTICIPANTS: In training, using reverse-transcriptase polymerase
      chain reaction (PCR), we compared the urine exosome gene expression assay with
      biopsy outcomes in 499 patients with prostate-specific antigen (PSA) levels of 2
      to 20 ng/mL. The derived prognostic score was then validated in 1064 patients
      from 22 community practice and academic urology clinic sites in the United
      States. Eligible participants included PCA-free men, 50 years or older, scheduled
      for an initial or repeated prostate needle biopsy due to suspicious digital
      rectal examination (DRE) findings and/or PSA levels (limit range, 2.0-20.0
      ng/mL). MAIN OUTCOMES AND MEASURES: Evaluate the assay using the area under
      receiver operating characteristic curve (AUC) in discrimination of GS7 or greater
      from GS6 and benign disease on initial biopsy. RESULTS: In 255 men in the
      training target population (median age 62 years and median PSA level 5.0 ng/mL,
      and initial biopsy), the urine exosome gene expression assay plus SOC was
      associated with improved discrimination between GS7 or greater and GS6 and benign
      disease: AUC 0.77 (95% CI, 0.71-0.83) vs SOC AUC 0.66 (95% CI, 0.58-0.72) (P <
      .001). Independent validation in 519 patients' urine exosome gene expression
      assay plus SOC AUC 0.73 (95% CI, 0.68-0.77) was superior to SOC AUC 0.63 (95% CI,
      0.58-0.68) (P < .001). Using a predefined cut point, 138 of 519 (27%) biopsies
      would have been avoided, missing only 5% of patients with dominant pattern 4 high
      risk GS7 disease. CONCLUSIONS AND RELEVANCE: This urine exosome gene expression
      assay is a noninvasive, urinary 3-gene expression assay that discriminates high
      grade (>=GS7) from low-grade (GS6) cancer and benign disease. In this study, the
      urine exosome gene expression assay was associated with improved identification
      of patients with higher-grade prostate cancer among men with elevated PSA levels
      and could reduce the total number of unnecessary biopsies.

PMID- 27032038
TI  - Psychosocial co-morbidities in adolescents and adults with histories of
      communication disorders.
AB  - BACKGROUND: Few studies have considered the long-term psychosocial outcomes of
      individuals with histories of early childhood speech sound disorders (SSD).
      Research on long-term psychosocial outcomes of individuals with language
      impairment (LI) have frequently failed to consider the effects of co-morbid SSD.
      The purpose of this study was to compare individuals with histories of SSD-only
      versus SSD with LI on these outcomes and to examine the contributions of other
      comorbid conditions including reading disorders (RD) and Attention Deficit
      Hyperactivity Disorder (ADHD). METHODS: Participants were adolescents aged 11-17
      years (N=129) and young adults aged 18-33 years (N=98). Probands with SSD were
      originally recruited between 4 and 6 years of age and classified into SSD-only
      and SSD+LI groups. Siblings of these children were also assessed at this time and
      those without SSD or LI were followed as controls. Outcome measures at
      adolescence and adulthood included ratings of hyperactivity, inattention,
      anxiety, and depression, as well as internalizing, externalizing, social, and
      thought problems. Adult outcomes also included educational and employment status
      and quality of life ratings. Regression modeling was performed to examine the
      association of SSD, LI, RD, and ADHD with psychosocial outcomes using Generalized
      Estimating Equations. RESULTS: In the adolescent group, LI was associated with
      poorer ratings of psychosocial problems on all scales except depression.
      Histories of SSD-only, RD and ADHD did not independently predict any of the
      adolescent psychosocial measures. In contrast, LI in the adult sample was not
      significantly associated with any of the behavior ratings, though RD was related
      to higher ratings of hyperactivity and inattention and with higher parent ratings
      of internalizing and externalizing symptoms and thought problems. SSD did not
      predict any of the adult measures once other comorbid conditions were taken into
      account. CONCLUSIONS: Poor adolescent psychosocial outcomes for individuals with
      early childhood SSD were primarily related to comorbid LI and not to SSD per se.
      At adulthood, comorbid RD and ADHD may influence outcomes more significantly than
      LI.

PMID- 27032039
TI  - Reprogramming Caspase-7 Specificity by Regio-Specific Mutations and Selection
      Provides Alternate Solutions for Substrate Recognition.
AB  - The ability to routinely engineer protease specificity can allow us to better
      understand and modulate their biology for expanded therapeutic and industrial
      applications. Here, we report a new approach based on a caged green fluorescent
      protein (CA-GFP) reporter that allows for flow-cytometry-based selection in
      bacteria or other cell types enabling selection of intracellular protease
      specificity, regardless of the compositional complexity of the protease. Here, we
      apply this approach to introduce the specificity of caspase-6 into caspase-7, an
      intracellular cysteine protease important in cellular remodeling and cell death.
      We found that substitution of substrate-contacting residues from caspase-6 into
      caspase-7 was ineffective, yielding an inactive enzyme, whereas saturation
      mutagenesis at these positions and selection by directed evolution produced
      active caspases. The process produced a number of nonobvious mutations that
      enabled conversion of the caspase-7 specificity to match caspase-6. The
      structures of the evolved-specificity caspase-7 (esCasp-7) revealed alternate
      binding modes for the substrate, including reorganization of an active site loop.
      Profiling the entire human proteome of esCasp-7 by N-terminomics demonstrated
      that the global specificity toward natural protein substrates is remarkably
      similar to that of caspase-6. Because the esCasp-7 maintained the core of caspase
      7, we were able to identify a caspase-6 substrate, lamin C, that we predict
      relies on an exosite for substrate recognition. These reprogrammed proteases may
      be the first tool built with the express intent of distinguishing exosite
      dependent or independent substrates. This approach to specificity reprogramming
      should also be generalizable across a wide range of proteases.

PMID- 27032040
TI  - The Perioperative Garden of Eden: Leading Edge or Trailing Edge?

PMID- 27032041
TI  - Perioperative Do-Not-Resuscitate Orders: Opportunity Knocks.

PMID- 27032042
TI  - Does the Modifier "QZ" Accurately Reflect Independent Nurse Anesthetist Practice:
      And Why Does It Matter?

PMID- 27032043
TI  - Correction to "Using FT-IR Spectroscopy to Measure Charge Organization in Ionic
      Liquids".

PMID- 27032045
TI  - Transition Patterns of Frailty Syndrome in Comunity-Dwelling Elderly Individuals:
      A Longitudinal Study.
AB  - BACKGROUND: Little information is available about transitional patterns related
      to frailty syndrome in elderly individuals living in the community. OBJECTIVE: To
      assess transitional patterns and determine which frailty phenotype variables are
      more involved in this process. DESIGN: Longitudinal study. POPULATION: Community
      dwelling elderly individuals in Belo Horizonte, Minas Gerais, Brazil.
      PARTICIPANTS: Two hundred individuals over 65 years old. MEASUREMENTS: The
      frailty phenotype was assessed at two different times, with a mean interval of 13
      months. Comparison of the frequency distributions between the baseline and second
      assessment was conducted through Pearson's chi-squared test, and a binary
      logistic regression was conducted to assess the most important items in this
      transition. RESULTS: Sixty-eight percent of the elderly were women, with an
      average age of 73.7 (+/- 6.1) years. The pre-frail group transitioned the most
      between evaluations. Eighty-five individuals transitioned among frailty levels:
      46 showed improvement while 39 worsened. Individuals who did scored low on the
      handgrip strength test in the first evaluation were more likely to have their
      frailty level worsen. Among individuals who showed improvements, those who were
      positive for weight loss and poor physical activity level in the first evaluation
      were less likely to improve. In this study, a greater number of individuals
      showed improved frailty levels over 13 months than worsened levels. CONCLUSION:
      Poor handgrip strength, weight loss, and poor physical activity are the most
      influential variables in frailty transitioning, leading to worsening levels of
      frailty or difficulty in making improvements.

PMID- 27032044
TI  - Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin
      Receptor Internalization Pathway.
AB  - DNA origami provides rapid access to easily functionalized, nanometer-sized
      structures making it an intriguing platform for the development of defined drug
      delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major
      obstacle in the development of DNA-based delivery platforms. Herein, significant
      strong increase in cellular uptake in an established cancer cell line by
      modifying a planar DNA origami structure with the iron transport protein
      transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled
      to the origami structure using a DNA-directed, site-selective labeling technique
      to retain ligand functionality. A combination of confocal fluorescence microscopy
      and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic
      uptake compared to unmodified structures and with an efficiency that correlates
      to the number of transferrin molecules on the origami surface.

PMID- 27032046
TI  - Gait Speed as a Predictor of Respiratory Muscle Function, Strength, and Frailty
      Syndrome in Community-Dwelling Elderly People.
AB  - BACKGROUND: Gait speed is considered a predictor of adverse health outcomes and
      functional decline in the elderly. This decline is also identified in respiratory
      muscles. OBJECTIVE: To assess the impact of gait speed in maximal inspiratory
      pressure, maximal expiratory pressure, handgrip strength, and the different types
      of frailty syndrome in community-dwelling elderly people. DESIGN: Cross-sectional
      study. PARTICIPANTS: Women (aged >= 65 years) were classified into different
      frailty phenotypes (n = 106). MEASUREMENTS: Gait speed (10 m), handgrip strength
      (Jamar dynamometer), and maximum inspiratory and expiratory pressures (GerAr
      manovacuometer, MV-150/300 model) were measured. Linear regression analyses were
      conducted to determine the influence of gait speed and age on handgrip strength,
      maximal inspiratory pressure, and maximal expiratory pressure. Logistic
      regression was performed to assess the influence of gait speed and frailty age
      (alpha = 0.05). RESULTS: A total of 106 elderly women participated in the study
      (73.96 +/- 6.91 years). Thirty-two subjects were not frail, 42 were pre-frail,
      and 32 were frail. Gait speed and age significantly predicted handgrip strength
      and frailty (p < 0.05). In the multivariate model, gait speed had the greatest
      contribution, while age lost statistical significance. Regarding maximal
      inspiratory and maximal expiratory pressures, gait speed and age were significant
      explanatory variables (p < 0.05). In the multivariate model, gait speed lost
      statistical significance to predict maximal inspiratory pressure. CONCLUSION:
      Gait speed was confirmed to be a predictor of some health outcomes, including
      respiratory muscle function. The results suggest that interventions to increase
      gait speed may contribute to improve respiratory function and muscle strength,
      and decrease the risk of frailty among elderly people.

PMID- 27032047
TI  - From Hospital to Home: Limited Nutritional and Functional Recovery for Older
      Adults.
AB  - BACKGROUND: The post-hospital period may be a vulnerable time for elders
      recovering from acute illness. Few studies have examined nutrition outcomes of
      older people at nutrition risk after acute hospitalisation. OBJECTIVES: This
      study aims to describe a) standard nutrition care received by recently discharged
      older medical patients, b) change in nutritional and functional status at six
      weeks post-discharge and c) clinical outcomes at twelve weeks post discharge.
      DESIGN: Prospective cohort study. SETTING: Two metropolitan teaching hospitals in
      Brisbane, Australia. PARTICIPANTS: Medical patients aged >=65 years at risk of
      malnutrition (Malnutrition Screening Score >=2) and discharged to independent
      living in the community. MEASUREMENT: Nutritional status (Mini Nutritional
      Assessment (MNA), weight, lean body mass), functional status (grip strength, walk
      speed, activities of daily living) and health-related quality of life assessed on
      discharge and six weeks post-discharge. Inpatient and post-discharge nutrition
      intervention was recorded. Death and unplanned admissions were measured at 12
      weeks. RESULTS: Of the 42 consented participants, only 14% (n=6) received post
      discharge dietitian review and 19% (n=8) received practical nutrition supports at
      home (meal delivery, shopping assistance) as part of standard care. While there
      was a small improvement in MNA (18.4+/-4.0 to 20.1+/-4.2, p=0.004) and walk speed
      (0.7+/-0.3 m/s to 0.9+/-0.3, p=0.004) at six weeks, there was no difference in
      mean weight, lean body mass, grip strength or activities of daily living. Five
      (15%) participants lost >=5% body weight. By twelve weeks, 17 participants (46%)
      had at least one unplanned hospital admission and four (10%) had died.
      CONCLUSIONS: Few patients at nutrition risk received nutrition-focussed care in
      the post-hospital period, and most did not improve nutritional or functional
      status at 6 weeks.

PMID- 27032048
TI  - 25-OH-Vitamin D Is Not Associated with Cognitive Performance among Mexican
      Community-Dwelling Older Persons.
AB  - BACKGROUND: Low cognitive performance has been associated with a wide array of
      adverse health-related outcomes in elderly populations. Recently, the effect of
      vitamin D on cognition has been studied; however, its benefits are still
      controversial. Moreover, most studies have been carried out on North-American and
      European populations where vitamin D deficiency could represent a greater public
      health issue when compared to Latin American ones. OBJECTIVE: To investigate the
      association between 25-OH-vitamin D and cognitive performance in Mexican
      community-dwelling elderly. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional
      study sample of 331 community-dwelling elderly aged 70 and older, participating
      in the Mexican Study of Nutritional and Psychosocial Markers of Frailty.
      MEASUREMENTS: Serum 25-OH-vitamin D, cognitive performance as per the Mini-Mental
      State Examination (MMSE) and the IST (Isaacs Set Test), as well as several
      elements from the comprehensive geriatric assessment. RESULTS: Mean age of
      participants was 79.3 years (SD 5.9), 54.1% were women. The mean serum 25-OH
      vitamin D level was 59.0 (SD 23.3) nmol/L while mean MMSE score was 22.3 (SD 3.4)
      and mean IST score was 37.1 (SD 9.1). Although 25-OH-vitamin D levels were lower
      across all the definitions of low cognitive perfomance, the difference between
      groups was not statistically significant in any of them. CONCLUSION: No
      association between 25-OH-vitamin D level and cognitive performance was found in
      this population of Mexican community-dwelling elderly. Further investigation is
      required in order to clarify its existence and if so, to delineate its
      characteristics.

PMID- 27032049
TI  - The Community Assessment of Risk Instrument: Investigation of Inter-Rater
      Reliability of an Instrument Measuring Risk of Adverse Outcomes.
AB  - BACKGROUND: Frailty is increasingly common in community dwelling older adults and
      increases their risk of adverse outcomes. Risk assessment is implicit in the Aged
      Care Assessment Teams process, but few studies have considered the factors that
      influence the assessor's decision making or explored the factors that may
      contribute to their interpretation of risk. OBJECTIVE: to examine the inter-rater
      reliability of the Community Assessment of Risk Instrument (CARI), which is a new
      risk assessment instrument. DESIGN: A cohort study was used. SETTING AND
      PARTICIPANTS: A sample of 50 community dwelling older adults underwent
      comprehensive geriatric assessment by two raters: a geriatrician and a registered
      nurse. Procedure and measurements: Each participant was scored for risk by the
      two raters using the CARI. This instrument ranks risk of three adverse outcomes,
      namely i) institutionalisation, ii) hospitalisation and iii) death within the
      next year from a score of 1, which is minimal risk to 5, which is extreme risk.
      Inter-rater reliability was assessed with Gamma, Spearman correlation and Kappa
      statistics. Internal consistency was assessed with Cronbach's alpha. RESULTS:
      There were 30 female (mean age 82.23 years) and 20 male (mean age 81.75 years)
      participants. Items within domains showed good-excellent agreement. The gamma
      statistic was >0.77 on 6/7 Mental State items, 14/15 items in the Activities of
      Daily Living domain. In the Medical domain, 6/9 items had Gamma scores >0.80. The
      global domain scores correlated well, 0.88, 0.72 and 0.87. Caregiver network
      scores were 0.71, 0.73 and 0.51 for the three domains. Inter-rater reliability
      scores for global risk scales were 0.86 (institutionalisation) and 0.78 (death).
      The gamma statistic for hospitalisation was 0.29, indicative of lower inter-rater
      reliability. Cronbach's alpha was 0.86 and 0.83 for the Activities of Daily
      Living domain, 0.51 and 0.42 for the Mental state domain and 0.23 and 0.10 for
      the Medical state domain. CONCLUSIONS: Overall, the instrument shows good inter
      rater reliability. Poor correlations on some items relate to poor communication
      of clinical data and variable interpretation based on professional background.
      Lack of internal consistency in the medical condition domain confirms the
      discrete nature of these variables.

PMID- 27032050
TI  - Frailty and Novel Technologies - A Step Ahead.
AB  - Dependence and disability are almost inevitable consequences of population aging.
      As these conditions are considered irreversible, a growing interest has been
      directed towards the identification of related conditions that are still amenable
      to preventive interventions. In this context, frailty has attracted an increasing
      scientific interest. Frailty is characterized by decreased homeostatic reserves
      and diminished resistance to stressors. The frail elderly constitutes a complex
      population in terms of assessment, monitoring, adherence to recommendations, and
      follow-up. The use of novel technologies may be considerably helpful for both
      clinical and research purposes. In particular, technologies may support
      interventions preventing disability, improving the quality of life, and enhancing
      the wellbeing of frail people. Traditional assessment instruments can be
      complemented or replaced by mobile devices measuring and monitoring frailty
      domains (e.g., physical performance, cognitive function, physical activity,
      nutritional status). Novel technologies have indeed the potential to benefit,
      assess, monitor, and support frail older people to live independently and improve
      their quality of life. 

PMID- 27032051
TI  - Unaltered Image of Health Maintenance: An Observation of Non-Participants in a
      Swedish Cohort Study of 85 to 86 Year Olds.
AB  - BACKGROUND: Selection bias is often inevitable in epidemiologic studies. It is
      not surprising that study conclusions based on participants' health status are
      frequently questioned. OBJECTIVE: This study aimed to assess whether the non
      participants affected the characteristics of a general population of the very old
      people. DESIGN, SETTING AND PARTICIPANTS: Prospective, cross-sectional (N=650,
      aged 85 years old) analysis and 1-year follow-up (n=273), in Linkoping, Sweden.
      MEASUREMENTS: We analysed data on health-related factors from a postal
      questionnaire, a home visit and a clinic visit at baseline and at the 1-year
      follow-up. We calculated the effect size to evaluate the degree of differences
      between the groups. RESULTS: A greater proportion of non-participants resided in
      sheltered accommodation or nursing homes (participants vs non-response vs
      refusal, 11% vs 22% vs 40, P<0.001, phi=0.24). During the home visit or clinic
      visit, a higher proportion of dropouts reported mid-severe problems in EQ-5D
      domains (mobility and self-care) and limitations in personal activities of daily
      living, but the differences between participants and dropouts were very small
      (phi<0.2). No significant difference was found between the groups with regard to
      emergency room visits or hospital admissions, despite the fact that more
      participants than dropouts (phi=0.23) had multimorbidities (>=2 chronic
      diseases). Living in sheltered accommodation or a nursing home (odds ratio (OR),
      2.8; 95% confidence interval (CI), 1.5-5), female gender (OR, 1.8; 95% CI, 1.1
      3.1) and receiving more home visits in primary care (OR, 1.03; 95% CI, 1-1.06)
      contributed positively to drop out in the data collection stages over the study
      period. CONCLUSION: Non-participants were not considered to be a group with worse
      health. Mobility problems may influence very old people when considering further
      participation, which threatens attrition.

PMID- 27032052
TI  - Nutrition and Frailty: A Review of Clinical Intervention Studies.
AB  - Frailty is one of the major health concerns in aging. It is considered a
      geriatric syndrome characterized by muscle weakness, sarcopenia and fatigue. It
      is also associated with several adverse health outcomes, including disability.
      Literature shows that there are a number of studies conducted to define the
      relationship between frailty and nutrition. The majority is from cross sectional,
      longitudinal, and cohort studies. Few intervention studies using micronutrients,
      macronutrients, nutritional supplement, or food regimens have been found. This
      review examines the nutrition intervention studies targeted towards older adults
      with frailty, and evaluates the effectiveness of nutrition interventions on
      frailty indicators. Twenty-four intervention studies from six electronic
      databases met the inclusion criteria. Sixteen were randomized controlled clinical
      trials; one was a quasi-experimental design, whilst the rest were controlled
      trials. Participants included in the studies differed in terms of age and frailty
      status. The studies were inconsistent in intervention type, duration, and
      targeted outcomes. Most of the studies indicated that modification of nutrition
      quality, either by giving supplements or by improving diet intake, could improve
      strength, walking speed, and nutritional status in majority of frail or pre-frail
      older adults. However, there was limited evidence on the effectiveness of
      intervention on inflammatory status and other biomarkers related to frailty due
      to limited number of studies targeting frailty biomarkers as a major outcome. 

PMID- 27032053
TI  - Erratum.

PMID- 27032054
TI  - Enantioselective Recognition for Many Different Kinds of Chiral Guests by One
      Chiral Receptor Based on Tetraphenylethylene Cyclohexylbisurea.
AB  - A neutral chiral receptor based on TPE cyclohexylbisurea was synthesized and
      could discriminate the enantiomers of many different kinds of chiral reagents,
      including chiral acidic compounds, basic compounds, amino acids, and even neutral
      alcohols. The (1)H NMR spectra disclosed that the ability of chiral recognition
      could be ascribed to the multiple hydrogen bonds and CH-pi interactions between
      the TPE urea receptor and the enantiomer of the chiral guest, which led to the
      selective aggregation of the receptor with one of the two enantiomers. This
      result exhibited a great potential in enantiomer discernment and high-throughput
      analysis of enantiomer composition of these chiral analytes by one chiral AIE
      molecule.

PMID- 27032055
TI  - Hereditary hemochromatosis: Dealing with iron overload.

PMID- 27032056
TI  - Immobilized Particle Imaging for Quantification of Nano- and Microparticles.
AB  - The quantification of nano- and microparticles is critical for diverse
      applications relying on the exact knowledge of the particle concentration.
      Although many techniques are available for counting particles, there are some
      limitations in regards to counting with low-scattering materials and facile
      counting in harsh organic solvents. Herein, we introduce an easy and rapid
      particle counting technique, termed "immobilized particle imaging" (IPI), to
      quantify fluorescent particles with different compositions (i.e., inorganic or
      organic), structures (i.e., solid, porous, or hollow), and sizes (50-1000 nm)
      dispersed in either aqueous or organic solutions. IPI is achieved by immobilizing
      particles of interest in a cell matrix-like scaffold (e.g., agarose) and imaging
      using standard microscopy techniques. Imaging a defined volume of the immobilized
      particles allows for the particle concentration to be calculated from the count
      numbers in a fixed volume. IPI provides a general and facile approach to quantify
      advanced nano- and microparticles, which may be helpful to researchers to obtain
      new insights for different applications (e.g., nanomedicine). 

PMID- 27032057
TI  - Choice of Emergency Contraceptive and Decision Making Regarding Subsequent
      Unintended Pregnancy.
AB  - OBJECTIVES: To prospectively evaluate (1) pregnancy desirability, (2) stated
      intentions should pregnancy occur among emergency contraception (EC) users, and
      (3) explore differences between women selecting the copper T380 intrauterine
      device (Cu IUD) or oral levonorgestrel (LNG) regarding hypothetical pregnancy
      plans and actual pregnancy actions during subsequent unintended pregnancies.
      STUDY DESIGN: In this prospective observational trial, women received the Cu IUD
      or oral LNG for EC without cost barriers. At baseline, participants completed a
      visual analogue scale measuring pregnancy desirability (anchors: 0, "trying hard
      not to get pregnant"; 10, "trying hard to get pregnant") and self-reported plans
      (abortion, adoption, parenting, and unsure) if the pregnancy test were to come
      back positive. Pregnancies were tracked for 12 months, and actions regarding
      unintended pregnancies were compared between EC method groups. RESULTS: Of 548
      enrolled women, 218 chose the Cu IUD and 330 the oral LNG for EC. Pregnancy
      desirability at baseline was low, with no difference between EC groups (IUD
      group: 0.51, SD +/- 1.60; LNG group: 0.68, SD +/- 1.74). Fifty-four (10%) women
      experienced unintended pregnancies. Pregnancy plans from baseline changed for 27
      (50%) women when they became pregnant. EC groups did not differ in hypothetical
      pregnancy intention (p = 0.15) or in agreement of hypothetical pregnancy
      intention with actual pregnancy action (p = 0.80). CONCLUSIONS: Women presenting
      for EC state high desire to prevent pregnancy regardless of method selected. When
      considering a hypothetical pregnancy, half of women had a plan for how they would
      respond to that situation, but when confronting an actual unintended pregnancy,
      half altered their plan. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov
      identifier NCT00966771.

PMID- 27032058
TI  - Thermally Stable Hierarchical Nanostructures of Ultrathin MoS2 Nanosheet-Coated
      CeO2 Hollow Spheres as Catalyst for Ammonia Decomposition.
AB  - MoS2 ultrathin nanosheet-coated CeO2 hollow sphere (CeO2@MoS2) hybrid
      nanostructures with a 3D hierarchical configuration were successfully constructed
      from a facile two-step wet chemistry strategy: first, CeO2 formed on a silica
      core which served as a template and was subsequently removed by NaOH solution to
      attain hollow spheres, and then few-layered ultrathin MoS2 nanosheets were
      deposited on the CeO2 hollow spheres through a hydrothermal process. As a proof
      of concept application, the as-prepared CeO2@MoS2 hybrid nanostructures were used
      as catalytic material, which exhibited enhanced catalytic activity in ammonia
      decomposition for H2 production at high temperature. It was demonstrated that,
      even with a structural transformation from MoS2 to MoNx under harsh conditions of
      ammonia decomposition at high temperature (700  degrees C), the 3D hierarchical
      nanostructures of the CeO2@MoNx were well kept, indicating the important role of
      the CeO2 support. 

PMID- 27032059
TI  - Recent advances and current state of immunotherapy in systemic lupus
      erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune syndrome that
      poses significant challenges in diagnosis and treatment. Dysregulated innate and
      adaptive immune systems are involved in its pathogenesis. A plethora of novel
      immunotherapies have been developed for the treatment of SLE but many have failed
      early clinical trials. AREAS COVERED: This review summarizes immunotherapies
      under recent development with relevance to the targeted cellular or soluble
      factors involved in the pathogenesis of SLE. EXPERT OPINION: SLE is a complicated
      disease with much heterogeneity. Novel immunotherapies with different mechanisms
      of action that are currently under development include biologic agents targeting
      co-stimulatory molecules, cytokines or their receptors and signaling molecules
      and B cells, cell-based therapy and peptide therapy. Together with good
      scientific rationale and advanced biological engineering techniques, optimization
      of clinical trial design, patient selection and disease outcome measures are
      essential to demonstrate the clinical efficacy and safety of these agents.

PMID- 27032060
TI  - The efficacy, safety and ethics of the use of testosterone-suppressing agents in
      the management of sex offending.
AB  - PURPOSE OF REVIEW: The use of endocrine medications to reduce sexual offending
      recidivism is established and may involve clinicians from diverse specialities.
      The present review aims to outline relevant background information and note a
      Medical Ethics framework upon which to facilitate decision-making. RECENT
      FINDINGS: There have been several systematic reviews in recent years. A number of
      problems with research in the area of the medical treatment of sex offenders have
      been highlighted. There remains scope for improvement in the research to answer a
      number of relevant clinical issues. Nonetheless, some very useful indicators of
      relevance to clinical practice have emerged. SUMMARY: The use of medication to
      manage the risk of sex offending in males is appropriate under the right
      circumstances. These include, for example, hypersexuality with sexual deviance
      and psychological-treatment interfering sexual preoccupation.

PMID- 27032061
TI  - Novel treatment strategies in congenital adrenal hyperplasia.
AB  - PURPOSE OF REVIEW: In recent years, important steps have been taken to improve
      the treatment of congenital adrenal hyperplasia (CAH), a relatively stagnant area
      for decades. In this review, we summarize these advances and propose future lines
      of investigation. RECENT FINDINGS: The two main goals of CAH treatment are to
      replace the deficient hormones when necessary and to dampen the
      adrenocorticotropin activation and the ensuing adrenal androgen excess.
      Glucocorticoids have been the mainstay of CAH treatment, but available
      preparations only partially meet the clinical needs. Recent efforts have focused
      on improving the delivery of glucocorticoid replacement agents, to closer mimic
      the physiologic secretion pattern. Examples include modified release oral
      glucocorticoids and continuous subcutaneous hydrocortisone pumps. Furthermore,
      nonglucocorticoid approaches to address the androgen excess have emerged, such as
      inhibition of key androgenic enzymes and adrenocorticotropin secretion blockade
      by corticotropin-releasing hormone receptor antagonists. SUMMARY: The promising
      recent progress made in CAH treatment brings new perspectives for individualized
      care in this complex disease.

PMID- 27032062
TI  - New insights into water oxidation reactions from photocatalysis, electrocatalysis
      to chemical catalysis: an example of iron-based oxides doped with foreign
      elements.
AB  - We have examined the catalytic activity of four different iron-based oxides doped
      with foreign elements using three common driving forces. The data clearly
      demonstrate that their water oxidation catalytic activity differ widely under
      different driving forces. 

PMID- 27032063
TI  - Oxytocin's effect on resting-state functional connectivity varies by age and sex.
AB  - The neuropeptide oxytocin plays a role in social cognition and affective
      processing. The neural processes underlying these effects are not well
      understood. Modulation of connectivity strength between subcortical and cortical
      regions has been suggested as one possible mechanism. The current study
      investigated effects of intranasal oxytocin administration on resting-state
      functional connectivity between amygdala and medial prefrontal cortex (mPFC), as
      two regions involved in social-cognitive and affective processing. Going beyond
      previous work that largely examined young male participants, our study comprised
      young and older men and women to identify age and sex variations in oxytocin's
      central processes. This approach was based on known hormonal differences among
      these groups and emerging evidence of sex differences in oxytocin's effects on
      amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective
      processing. In a double-blind design, 79 participants were randomly assigned to
      self-administer either intranasal oxytocin or placebo before undergoing resting
      state functional magnetic resonance imaging. Using a targeted region-to-region
      approach, resting-state functional connectivity strength between bilateral
      amygdala and mPFC was examined. Participants in the oxytocin compared to the
      placebo group and men compared to women had overall greater amygdala-mPFC
      connectivity strength at rest. These main effects were qualified by a significant
      three-way interaction: while oxytocin compared to placebo administration
      increased resting-state amygdala-mPFC connectivity for young women, oxytocin did
      not significantly influence connectivity in the other age-by-sex subgroups. This
      study provides novel evidence of age-by-sex differences in how oxytocin modulates
      resting-state brain connectivity, furthering our understanding of how oxytocin
      affects brain networks at rest.

PMID- 27032064
TI  - Effects of positive and negative human contacts and intranasal oxytocin on
      cerebrospinal fluid oxytocin.
AB  - Despite the popularity of oxytocin (OT) research for its role in social behavior,
      the relationship between the social environment and endogenous central OT remains
      poorly understood. This study investigated the effects of positive and negative
      human contacts and intranasal OT administration on OT concentration in the
      cerebrospinal fluid (CSF). The pig was used as a model, with repeated CSF
      sampling through a spinal catheter using a within-subject design. Positive human
      contact led to sustained CSF OT elevation in pigs over 120min which outlasted the
      15min interaction. Furthermore, the frequency of positive interactions was
      correlated with CSF OT increase. This provides a neurophysiological basis to
      positive human-animal relationships, with OT preserving bonds within but also
      between species through interactions. Conversely, CSF OT concentration did not
      vary during or after negative contact with an unfamiliar person, supporting CSF
      OT as a biomarker of positive valence in the human-animal relationship context.
      Intranasal OT administration resulted in peak CSF OT within 10min, with
      approximately 0.001% of the administered dose reaching the CSF. The sensitivity
      of the oxytocinergic system to variations in the social environment is a worthy
      area of investigation for its scientific and clinical implications. In
      particular, positive interactions result in outlasting central OT release.

PMID- 27032065
TI  - Microfluidic techniques for high throughput single cell analysis.
AB  - The microfabrication of microfluidic control systems and the development of
      increasingly sensitive molecular amplification tools have enabled the
      miniaturization of single cells analytical platforms. Only recently has the
      throughput of these platforms increased to a level at which populations can be
      screened at the single cell level. Techniques based upon both active and passive
      manipulation are now capable of discriminating between single cell phenotypes for
      sorting, diagnostic or prognostic applications in a variety of clinical
      scenarios. The introduction of multiphase microfluidics enables the segmentation
      of single cells into biochemically discrete picoliter environments. The
      combination of these techniques are enabling a class of single cell analytical
      platforms within great potential for data driven biomedicine, genomics and
      transcriptomics.

PMID- 27032066
TI  - A sensitive and versatile method for characterization of protein-mediated
      transformations of quantum dots.
AB  - We report the development and application of an analytical system consisting of
      capillary electrophoresis (CE) interfaced with inductively coupled plasma mass
      spectrometry (ICP-MS) for sensitive and high-resolution characterization of
      quantum dots (QDs) interacting with serum proteins. Separation resolution between
      the intact CdSeS/ZnS QDs and their protein conjugates was optimized by varying
      the type and concentration of background electrolyte, applied voltage, and sample
      loading. Special attention was paid to the CE system compatibility with
      physiological conditions, avoiding aggregation effects, and analyte recovery.
      Optimization trials allowed for acquiring satisfactory stability of migration
      times (within 6.0% between different days), peak area precision of 5.2-8.0%,
      capillary recoveries in the range of 90-96%, and a lower limit of detection of
      7.5 * 10(-9) mol L(-1) Cd. With the developed method distinct metal-specific
      profiles were obtained for the QDs in combination with individual serum proteins,
      their mixtures, and in human serum. Particularly, it was found that albumin
      binding to the particle surface is completed after 1 h, without noticeable
      disruption of the core-shell integrity. The transferrin adsorption is accompanied
      by the removal of the ZnS shell, resulting in evolving two different metal
      protein conjugated forms. On the other hand, proteinization in real-serum
      environment occurs without binding to major transport proteins, the QDs also lose
      their the shell (the higher the dose the longer is the time they stay unbroken).
      The concomitant changes in migration behavior can be attributed to interactions
      with serum proteins other than albumin and transferrin. Speciation information
      provided by CE-ICP-MS may shed light on the mechanism of QD delivery to the
      target regions of the body. 

PMID- 27032067
TI  - Hydrangenol inhibits lipopolysaccharide-induced nitric oxide production in BV2
      microglial cells by suppressing the NF-kappaB pathway and activating the Nrf2
      mediated HO-1 pathway.
AB  - We previously demonstrated the anti-inflammatory effect of water extract of
      Hydrangea macrophylla in lipopolysaccharide (LPS)-stimulated macrophage cells.
      Here, we investigated whether hydrangenol, a bioactive component of H.
      macrophylla, attenuates the expression of nitric oxide (NO) and its associated
      gene, inducible NO synthase (iNOS), in LPS-stimulated BV2 microglial cells. Our
      data showed that low dosages of hydrangenol inhibited LPS-stimulated NO release
      and iNOS expression without any accompanying cytotoxicity. Hydrangenol also
      suppressed LPS-induced nuclear translocation of nuclear factor-kappaB (NF-kappaB)
      subunits, consequently inhibiting DNA-binding activity of NF-kappaB.
      Additionally, the NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC) and PS
      1145, significantly attenuated LPS-induced iNOS expression, indicating that
      hydrangenol-induced NF-kappaB inhibition might be a key regulator of iNOS
      expression. Furthermore, our data showed that hydrangenol suppresses NO
      production by inducing heme oxygenase-1 (HO-1). The presence of cobalt
      protoporphyrin, a specific HO-1 inducer, potently suppressed LPS-induced NO
      production. Hydrangenol also promoted nuclear translocation of nuclear factor
      erythroid 2-related factor 2 (Nrf2) and subsequently increased its binding
      activity at the specific antioxidant response element sites. Additionally,
      transient knockdown of Nrf2 significantly downregulated hydrangenol-induced HO-1
      expression, indicating that hydrangenol-induced Nrf2 is an upstream regulator of
      HO-1. Taken together, these data suggest that hydrangenol attenuates NO
      production and iNOS expression in LPS-stimulated BV2 microglial cells by
      inhibiting NF-kappaB activation and by stimulating the Nrf2-mediated HO-1
      signaling pathway. Therefore, hydrangenol is a promising therapeutic agent for
      treatment of LPS-mediated inflammatory diseases. 

PMID- 27032068
TI  - Efficient Light-Driven Oxidation of Alcohols Using an Organic Chromophore
      Catalyst Assembly Anchored to TiO2.
AB  - The ligand 5-PO3H2-2,2':5',2"-terthiophene-5-trpy, T3 (trpy = 2,2':6',2"
      terpyridine), was prepared and studied in aqueous solutions along with its metal
      complex assembly [Ru(T3)(bpy)(OH2)](2+) (T3-Ru-OH2, bpy = 2,2'-bipyridine). T3
      contains a phosphonic acid group for anchoring to a TiO2 photoanode under aqueous
      conditions, a terthiophene fragment for light absorption and electron injection
      into TiO2, and a terminal trpy ligand for the construction of assemblies
      comprising a molecular oxidation catalyst. At a TiO2 photoanode, T3 displays
      efficient injection at pH 4.35 as evidenced by the high photocurrents (~350
      uA/cm(2)) arising from hydroquinone oxidation. Addition of [Ru(bpy)(OTf)][OTf]2
      (bpy = 2,2'-bipyridine, OTf(-) = triflate) to T3 at the free trpy ligand forms
      the molecular assembly, T3-Ru-OH2, with the oxidative catalyst fragment:
      [Ru(trpy)(bpy)(OH2)](2+). The new assembly, T3-Ru-OH2, was used to perform
      efficient light-driven oxidation of phenol (230 MUA/cm(2)) and benzyl alcohol (25
      MUA/cm(2)) in a dye-sensitized photoelectrosynthesis cell. 

PMID- 27032069
TI  - Negative regulation of TCR signaling by ubiquitination of Zap-70 Lys-217.
AB  - The tyrosine kinase Zap-70 is a key regulator of T cell receptor (TCR) signaling
      downstream of antigen presentation, with coordinated regulation of Zap-70 kinase
      activity critical for proper T cell proliferation, differentiation, and effector
      function during an immune response. Zap-70 is cytosolic in unstimulated T cells,
      but is rapidly recruited to the TCR complex following receptor stimulation. Its
      activity is regulated both by binding to subunits of the TCR and by
      phosphorylation on multiple tyrosine residues. Zap-70 also has been reported to
      be ubiquitinated following TCR stimulation. Herein, we confirm the ubiquitination
      of Zap-70 in T cell lines and in primary human and mouse T cells, and report the
      identification of nine novel Zap-70 ubiquitination sites. Three sites, including
      Lys-193, Lys-217, and Lys-376, displayed greater than 20-fold increase in
      modification levels following TCR stimulation. Abrogation of Lys-217
      ubiquitination results in increased kinase activation, enhanced activation of
      downstream signaling pathways, and elevated IL-2 production following TCR
      stimulation. These data suggest that Zap-70 ubiquitination contributes to the
      regulation of Zap-70 signaling following TCR stimulation.

PMID- 27032070
TI  - Molecular Gold Wire from Mixed-Valent Au(I/III) Complexes.
AB  - Crystals of mixed-valent Au complexes have been grown from solutions of
      cyclohexanecarbonitrile and a stoichiometric amount of gold(I) and gold(III)
      chloride. The purely obtained compound was characterized as
      bis(cyclohexanecarbonitrile)gold(I) tetrachloridoaurate(III). The crystal packing
      of the mixed valent Au(I/III) compound demonstrates a columnar arrangement of the
      gold(I) and gold(III) atoms. The new structure displays the shortest unsupported
      gold(I)-gold(III) interactions with the sub-van der Waals distance of 324-325 pm,
      which is assumed as an aurophilic bonding interaction. 

PMID- 27032071
TI  - Effects of dietary cadmium on growth, antioxidants and bioaccumulation of sea
      cucumber (Apostichopus japonicus) and influence of dietary vitamin C
      supplementation.
AB  - The effects of dietary cadmium (Cd) supplementation on growth, antioxidant
      capacity and accumulation of Cd in tissues (body wall, digestive tracts, and
      respiratory tree) of sea cucumber, Apostichopus japonicus, exposed to sub-chronic
      concentrations (0, 10, 50, 100, and 500mg Cd/kg dry weight) of Cd were
      investigated. In addition, the potential protective effects of vitamin C (L
      ascorbic acid, AsA) against the effects of Cd on sea cucumbers were investigated.
      Sea cucumbers were exposed to dietary Cd for 30 days, after which another group
      of healthy sea cucumbers was supplied diet supplemented with mixed Cd and AsA for
      another 30 days. Cd exposure for 30 days resulted in increased Cd accumulation in
      tissues of sea cucumbers with exposure time and concentration. The order of Cd
      accumulation in organs was digestive tracts>respiratory tree>body wall. On day
      30, the body weight gain (BWG) and specific growth rate (SGR) decreased
      significantly (P<0.05) in the 500mg Cd/kg treatment. Superoxide dismutase (SOD)
      activity, glutathione peroxidase (GSH-Px) activity and catalase (CAT) activity in
      the coelomic fluid of sea cucumbers decreased with increasing dietary Cd
      concentration, but malondialdehyde (MDA) content in the coelomic fluid increased.
      Providing diet supplemented with Cd and AsA indicated that although sea cucumbers
      exhibited signs of Cd toxicity, no death occurred in response to 50mg Cd/kg for
      30 days. Based on these findings, five treatments were provided: 50mg Cd/kg+0mg
      AsA/kg, 50mg Cd/kg+ 3000mg AsA/kg, 50mg Cd/kg+ 5000mg AsA/kg, 50mg Cd/kg+10,000mg
      AsA/kg, and 50mg Cd/kg+15,000mg AsA/kg. The BWG and SGR of sea cucumbers fed the
      AsA supplemented diet mixed with Cd increased. Additionally, MDA levels in
      coelomic fluid were negatively correlated with dietary AsA levels, while
      antioxidant capacities (SOD, GSH-Px and CAT) were positively correlated with
      dietary AsA levels. Moreover, Cd accumulation in tissues decreased in response to
      dietary AsA supplementation of treatments. Overall, antioxidant capacity and
      bioaccumulation in sea cucumber was found to decrease and be induced in response
      to Cd, but vitamin C mitigated these effects, with 5000mg AsA/kg providing the
      optimum protection against 50mg/kg Cd.

PMID- 27032072
TI  - Chemical multi-contamination drives benthic prokaryotic diversity in the
      anthropized Toulon Bay.
AB  - Investigating the impact of human activities on marine coastal ecosystems remains
      difficult because of the co-occurrence of numerous natural and human-induced
      gradients. Our aims were (i) to evaluate the links between the chemical
      environment as a whole and microbial diversity in the benthic compartment, and
      (ii) to compare the contributions of anthropogenic and natural chemical gradients
      to microbial diversity shifts. We studied surface sediments from 54 sampling
      sites in the semi-enclosed Toulon Bay (NW Mediterranean) exposed to high
      anthropogenic pressure. Previously published chemical data were completed by new
      measurements, resulting in an in depth geochemical characterization by 29
      representative environmental variables. Bacterial and archaeal diversity was
      assessed by terminal restriction fragment length polymorphism profiling on a
      selection of samples distributed along chemical gradients. Multivariate
      statistical analyses explained from 45% to 80% of the spatial variation in
      microbial diversity, considering only the chemical variables. A selection of
      trace metals of anthropogenic origin appeared to be strong structural factors for
      both bacterial and archaeal communities. Bacterial terminal restriction fragment
      (T-RF) richness correlated strongly with both anthropogenic and natural chemical
      gradients, whereas archaeal T-RF richness demonstrated fewer links with chemical
      variables. No significant decrease in diversity was evidenced in relation to
      chemical contamination, suggesting a high adaptive potential of benthic microbial
      communities in Toulon Bay. 

PMID- 27032073
TI  - Orthostatic changes in blood pressure and mortality in a nursing home population.
AB  - OBJECTIVE: Hypertension, orthostatic hypotension and orthostatic hypertension
      (OHT) are highly prevalent in old age. The associations in the very elderly and
      frail patients between blood pressure, and especially orthostatic changes in
      blood pressure, and mortality are unclear. We aimed to investigate the
      relationships between orthostatic changes in blood pressure, blood pressure and
      mortality in nursing home residents. DESIGN AND METHODS: A prospective
      observational cohort study. Cox proportional hazard modelling was used to
      investigate the relation between orthostatic hypotension, OHT, the various blood
      pressure variables and mortality with adjustment for confounders. In the case of
      significant associations in the models, risk prediction capabilities were
      assessed with Harrell's C statistics and the proportion of explained variance
      (R). RESULTS: Two hundred and ninety patients with a mean age of 80.8 (SD 9.9)
      years participated in this study. The overall mortality risk increased by 17%
      [95% confidence interval (CI): 2-34%] for every 10-mmHg increase in DBP. Adding
      DBP did not change Harrell's C values and increased R with 0.03 or less. Only in
      patients at the psychogeriatric department, orthostatic hypotension was
      associated with an increased all-cause mortality risk [hazard ratio (HR) 1.71
      (95% CI: 1.08-2.71%)]. The HR of OHT in this patient group was 0.61 (95% CI: 0.32
      1.19%). CONCLUSION: DBP was related to all-cause mortality in a nursing home
      population. Orthostatic hypotension was related to all-cause mortality in the
      most frail group of nursing home patients. The predictive capabilities of both
      DBP and orthostatic hypotension are rather small with respect to mortality. A
      beneficial effect of OHT could not be excluded on the basis of the width of the
      CI.

PMID- 27032074
TI  - Antihypertensive medications and sexual function in women: baseline data from the
      SBP intervention trial (SPRINT).
AB  - OBJECTIVES: Hypertension is a risk factor for the development of cardiovascular
      and kidney disease, but treatment can substantially reduce risks. Many patients
      avoid antihypertensive medications because of fear of side-effects. Although
      associations between antihypertensives and sexual dysfunction in men have been
      documented, it remains unclear whether antihypertensives are associated with
      sexual dysfunction in women. We conducted a cross-sectional analysis of baseline
      data from women in the Systolic Blood Pressure Intervention Trial (SPRINT) to
      evaluate the relations among class of antihypertensive medication and the
      outcomes: sexual activity and sexual function. METHODS: SPRINT enrolled
      individuals 50 and older with hypertension at high risk for cardiovascular
      disease. A subset of participants completed questionnaires regarding quality of
      life, including sexual function. Antihypertensive class was determined by
      medications taken at baseline. RESULTS: Of 690 women in the quality of life
      subset of SPRINT, 183 (26.5%) were sexually active. There were no significant
      differences in sexual activity among women taking one or more antihypertensives
      and women not taking any. Women taking an angiotensin-converting enzyme inhibitor
      or angiotensin receptor blocker had higher odds of sexual activity [odds ratio
      1.66 (1.12-4.27), P = 0.011]. Among sexually active women, the prevalence of
      sexual dysfunction was high (52.5%). No class of medication was associated with
      sexual dysfunction in the multivariable model. CONCLUSION: Angiotensin-converting
      enzyme inhibitor or angiotensin receptor blocker use was associated with higher
      odds of sexual activity. Although prevalence of sexual dysfunction was high, no
      single class of antihypertensive medication was associated with sexual
      dysfunction.

PMID- 27032075
TI  - Renal hemodynamics and renin-angiotensin system activity in humans with
      multifocal renal artery fibromuscular dysplasia.
AB  - BACKGROUND: Fibromuscular dysplasia (FMD) is the second most common cause of
      renovascular hypertension. Nonetheless, knowledge on the renal microvasculature
      and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given
      the fairly good results of revascularization, we hypothesized that the renal
      microvasculature and RAS are relatively spared in kidneys with FMD. METHOD: In 58
      hypertensive patients with multifocal renal artery FMD (off medication) and 116
      matched controls with essential hypertension, we measured renal blood flow (Xenon
      washout method) per kidney and drew blood samples from the aorta and both renal
      veins to determine renin secretion and glomerular filtration rate per kidney.
      RESULTS: We found that renal blood flow and glomerular filtration rate in FMD
      were comparable to those in controls. Although systemic renin levels were
      somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in
      patients with unilateral FMD, no differences between the affected and unaffected
      kidney were observed with regard to renal blood flow, glomerular filtration rate,
      or renin secretion. In men, renin levels and renin secretion were higher as
      compared with women. The renal blood flow response to RAS modulation (by
      intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type
      1 receptor blocker, or a nitric oxide synthase blocker) was also comparable
      between FMD and controls. CONCLUSION: Renal blood flow, glomerular filtration,
      and the response to vasoactive substances in kidneys with multifocal FMD are
      comparable to patients with essential hypertension, suggesting that microvascular
      function is relatively spared. Renin secretion was not increased and the response
      to RAS modulation was not affected in kidneys with FMD.

PMID- 27032076
TI  - Serum zinc concentrations and incident hypertension: new findings from a
      population-based cohort study.
AB  - OBJECTIVE: Zinc is an essential trace element that plays a key role in several
      cellular processes and has been suggested to be involved in blood pressure
      regulation. We aimed to prospectively investigate the association between
      baseline concentrations of serum zinc and incident hypertension. METHODS: We
      analyzed data involving 1652 men aged 42-61 years without a known history of
      hypertension at baseline in the Kuopio Ischemic Heart Disease population-based
      cohort study, with the assessment of serum zinc concentrations. Hazard ratios
      [95% confidence intervals (CIs)] for incident hypertension were assessed.
      RESULTS: During a median follow-up of 24.7 years, 259 participants developed
      hypertension. Serum zinc was weakly correlated with several risk markers for
      hypertension and nonlinearly associated with incident hypertension. In analyses
      adjusted for age, the hazard ratio (95% CIs) for hypertension in a comparison of
      the top quartile vs. bottom quartiles 1-3 of zinc concentration was 1.65 (1.27
      2.15; P < 0.001), which was minimally attenuated on adjustment for several
      established risk factors 1.48 (1.13-1.93; P = 0.004). The association remained
      unchanged on further adjustment for renal function, socioeconomic status, and
      dietary factors. The findings were generally consistent across several clinical
      subgroups. There was no evidence of an association of dietary zinc intake with
      risk of hypertension. CONCLUSION: This prospective study suggests higher serum
      zinc concentration is positively and independently associated with incident
      hypertension in men. Further evidence from large-scale population-based studies
      is needed to support these findings and assess the mechanisms underlying the
      association.

PMID- 27032077
TI  - Bioactivation of Heterocyclic Aromatic Amines by UDP Glucuronosyltransferases.
AB  - 2-Amino-9H-pyrido[2,3-b]indole (AalphaC) and 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise
      during the burning of tobacco and cooking of meats. UDP-glucuronosyltransferases
      (UGT) detoxicate many procarcinogens and their metabolites. The genotoxic N
      hydroxylated metabolite of AalphaC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH
      AalphaC), undergoes glucuronidation to form the isomeric glucuronide (Gluc)
      conjugates N(2)-(beta-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole
      (AalphaC-HON(2)-Gluc) and O-(beta-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3
      b]indole (AalphaC-HN(2)-O-Gluc). AalphaC-HON(2)-Gluc is a stable metabolite but
      AalphaC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently
      adducts to DNA at levels that are 20-fold higher than HONH-AalphaC. We measured
      the rates of formation of AalphaC-HON(2)-Gluc and AalphaC-HN(2)-O-Gluc in human
      organs: highest activity occurred with liver and kidney microsomes, and lesser
      activity was found with colon and rectum microsomes. AalphaC-HN(2)-O-Gluc
      formation was largely diminished in liver and kidney microsomes, by niflumic
      acid, a selective inhibitor UGT1A9. In contrast, AalphaC-HON(2)-Gluc formation
      was less affected and other UGT contribute to N(2)-glucuronidation of HONH
      AalphaC. UGT were reported to catalyze the formation of isomeric Gluc conjugates
      at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. However, we found that
      the N3-Gluc of HONH-PhIP also covalently bound to DNA at higher levels than HONH
      PhIP. The product ion spectra of this Gluc conjugate acquired by ion trap mass
      spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH
      PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was
      originally proposed. UGT1A9, an abundant UGT isoform expressed in human liver and
      kidney, preferentially forms the O-linked Gluc conjugates of HONH-AalphaC and
      HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. The regioselective O
      glucuronidation of HONH-AalphaC and HONH-PhIP, by UGT1A9, is a mechanism of
      bioactivation of these ubiquitous HAAs.

PMID- 27032078
TI  - Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus-
      United States, 2016.
AB  - CDC issued interim guidance for the prevention of sexual transmission of Zika
      virus on February 5, 2016. The following recommendations apply to men who have
      traveled to or reside in areas with active Zika virus transmission and their
      female or male sex partners. These recommendations replace the previously issued
      recommendations and are updated to include time intervals after travel to areas
      with active Zika virus transmission or after Zika virus infection for taking
      precautions to reduce the risk for sexual transmission. This guidance defines
      potential sexual exposure to Zika virus as any person who has had sex (i.e.,
      vaginal intercourse, anal intercourse, or fellatio) without a condom with a man
      who has traveled to or resides in an area with active Zika virus transmission.
      This guidance will be updated as more information becomes available.

PMID- 27032079
TI  - Pedobacter humi sp. nov., isolated from a playground soil.
AB  - A Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented
      bacterium, designated strain THG S15-2T, was isolated from playground soil in
      Sindorim-dong, Guro-gu, Seoul, South Korea. According to 16S rRNA gene sequence
      comparisons, strain THG S15-2T was found to be related most closely to Pedobacter
      ginsengisoli Gsoil 104T (97.5 % similarity), Pedobacter panaciterrae Gsoil 042T
      (97.4 %), Pedobacter seoulensis THG-G12T (97.1 %) and Pedobacter caeni LMG 22862T
      (97.1 %). The level of DNA-DNA relatedness between strain THG S15-2T and its
      phylogenetically closest neighbours was below 30.0 %. The only isoprenoid quinone
      detected in strain THG S15-2T was menaquinone-7. The DNA G+C content was 45.9
      mol%. The major polar lipid was phosphatidylethanolamine. The major component in
      the polyamine pattern was sym-homospermidine. The major fatty acids were
      identified as summed feature 3 (C16:1omega7c and/or C16:1omega6c), iso-C15:0 and
      C16:0. These data supported the affiliation of strain THG S15-2T to the genus
      Pedobacter. Strain THG S15-2T was distinguished from related Pedobacter species
      by physiological and biochemical tests. Therefore, strain THG S15-2T represents a
      novel species, for which the name Pedobacter humi sp. nov. is proposed. The type
      strain is THG S15-2T (= KCTC 42735T = CCTCC AB 2015293T). 

PMID- 27032080
TI  - The role of digital data entry in participatory environmental monitoring.
AB  - Many argue that monitoring conducted exclusively by scientists is insufficient to
      address ongoing environmental challenges. One solution entails the use of mobile
      digital devices in participatory monitoring (PM) programs. But how digital data
      entry affects programs with varying levels of stakeholder participation, from
      nonscientists collecting field data to nonscientists administering every step of
      a monitoring program, remains unclear. We reviewed the successes, in terms of
      management interventions and sustainability, of 107 monitoring programs described
      in the literature (hereafter programs) and compared these with case studies from
      our PM experiences in Australia, Canada, Ethiopia, Ghana, Greenland, and Vietnam
      (hereafter cases). Our literature review showed that participatory programs were
      less likely to use digital devices, and 2 of our 3 more participatory cases were
      also slow to adopt digital data entry. Programs that were participatory and used
      digital devices were more likely to report management actions, which was
      consistent with cases in Ethiopia, Greenland, and Australia. Programs engaging
      volunteers were more frequently reported as ongoing, but those involving digital
      data entry were less often sustained when data collectors were volunteers. For
      the Vietnamese and Canadian cases, sustainability was undermined by a mismatch in
      stakeholder objectives. In the Ghanaian case, complex field protocols diminished
      monitoring sustainability. Innovative technologies attract interest, but the
      foundation of effective participatory adaptive monitoring depends more on
      collaboratively defined questions, objectives, conceptual models, and monitoring
      approaches. When this foundation is built through effective partnerships, digital
      data entry can enable the collection of more data of higher quality. Without this
      foundation, or when implemented ineffectively or unnecessarily, digital data
      entry can be an additional expense that distracts from core monitoring objectives
      and undermines project sustainability. The appropriate role of digital data entry
      in PM likely depends more on the context in which it is used and less on the
      technology itself.

PMID- 27032081
TI  - A Wormian Bone, Mimicking an Entry Gunshot Wound of the Skull, in an
      Anthropological Specimen.
AB  - Wormian bones (WB) are irregular small cranial ossicles found along suture lines
      and fontanels. In Brazil, gunshot wounds to the skull are quite common in young
      individuals. Nevertheless, as far as we know, this is the first report of a WB
      giving an erroneous aspect of gunshot entrance due to its displacement position.
      The present manuscript describes the case of a Brazilian young man who died due
      to ballistic trauma, where a gaping bony defect on the right side of the skull
      was thought to be the exit wound of an injury related to the destruction found on
      the left side, highly suggestive of firearm injury. Thus, this case study has
      brought to light similarities between a traumatic lesion and an orifice of a WB,
      with emphasis on differential diagnosis during routine anthropological
      examinations.

PMID- 27032082
TI  - The association of serum cathepsin B concentration with age-related
      cardiovascular-renal subclinical state in a healthy Chinese population.
AB  - CONTEXT: Cathepsin B (CTSB) is an important enzyme for many physiological and
      pathological processes, and its activity increases with age. Here, we explored
      the association between serum CTSB and aging-related subclinical cardiovascular
      and renal status in a healthy Chinese population. METHODS: The study included 369
      healthy individuals aged 36-87 years. Cardiovascular structure and function were
      assessed by the left ventricular ejection fraction, the early-diastolic peak flow
      velocity to late-diastolic peak flow velocity ratio at the mitral leaflet tips,
      carotid intima-media thickness (IMT), the diameter of the bilateral common
      carotid artery (D), and blood systolic peak (SPV) and end diastolic velocities,
      which were measured by M-mode ultrasonography. Serum CTSB, insulin-like growth
      factor-1 (IGF-1), 1, 25-dihydroxy vitamin D3, and parathyroid hormone (PTH) were
      measured by enzyme-linked immunosorbent assay. RESULTS: In men, serum CTSB was
      significantly related to IMT and IMT/D in the unadjusted model, and these
      associations were lost after age adjustment. In women, serum CTSB remained
      significantly associated with serum creatinine (SCr) (p=0.009), estimated
      glomerular filtration rate (p=0.048) and IMT/D (p=0.017) following full
      adjustment. PTH was independently associated with SCr. IGF-1 was significantly
      associated with SPV in women. CTSB was correlated with metabolic and endocrine
      biomarkers. CONCLUSION: Serum CTSB was associated with aging-related
      cardiovascular-renal parameters even in healthy people. Measurement of serum CTSB
      alone or in combination with metabolic and endocrine biomarkers can provide
      valuable information for predicting cardiovascular-renal function in healthy
      people, especially in elderly women.

PMID- 27032083
TI  - Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype.
AB  - Platelet-derived growth factor D (PDGF-D) is the most recently discovered member
      of the PDGF family. PDGF-D signals through PDGF receptor beta, but its biological
      role remains largely unknown. In contrast to other members of the PDGF family of
      growth factors, which have been extensively investigated using different knockout
      approaches in mice, PDGF-D has until now not been characterized by gene
      inactivation in mice. Here, we present the phenotype of a constitutive Pdgfd
      knockout mouse model (Pdgfd-/-), carrying a LacZ reporter used to visualize Pdgfd
      promoter activity. Inactivation of the Pdgfd gene resulted in a mild phenotype in
      C57BL/6 mice, and the offspring was viable, fertile and generally in good health.
      We show that Pdgfd reporter gene activity was consistently localized to vascular
      structures in both postnatal and adult tissues. The expression was predominantly
      arterial, often localizing to vascular bifurcations. Endothelial cells appeared
      to be the dominating source for Pdgfd, but reporter gene activity was
      occasionally also found in subpopulations of mural cells. Tissue-specific
      analyses of vascular structures revealed that NG2-expressing pericytes of the
      cardiac vasculature were disorganized in Pdgfd-/- mice. Furthermore, Pdgfd-/-
      mice also had a slightly elevated blood pressure. In summary, the vascular
      expression pattern together with morphological changes in NG2-expressing cells,
      and the increase in blood pressure, support a function for PDGF-D in regulating
      systemic arterial blood pressure, and suggests a role in maintaining vascular
      homeostasis. 

PMID- 27032084
TI  - NREM2 and Sleep Spindles Are Instrumental to the Consolidation of Motor Sequence
      Memories.
AB  - Although numerous studies have convincingly demonstrated that sleep plays a
      critical role in motor sequence learning (MSL) consolidation, the specific
      contribution of the different sleep stages in this type of memory consolidation
      is still contentious. To probe the role of stage 2 non-REM sleep (NREM2) in this
      process, we used a conditioning protocol in three different groups of
      participants who either received an odor during initial training on a motor
      sequence learning task and were re-exposed to this odor during different sleep
      stages of the post-training night (i.e., NREM2 sleep [Cond-NREM2], REM sleep
      [Cond-REM], or were not conditioned during learning but exposed to the odor
      during NREM2 [NoCond]). Results show that the Cond-NREM2 group had significantly
      higher gains in performance at retest than both the Cond-REM and NoCond groups.
      Also, only the Cond-NREM2 group yielded significant changes in sleep spindle
      characteristics during cueing. Finally, we found that a change in frequency of
      sleep spindles during cued-memory reactivation mediated the relationship between
      the experimental groups and gains in performance the next day. These findings
      strongly suggest that cued-memory reactivation during NREM2 sleep triggers an
      increase in sleep spindle activity that is then related to the consolidation of
      motor sequence memories. 

PMID- 27032085
TI  - Proteins in the Cocoon of Silkworm Inhibit the Growth of Beauveria bassiana.
AB  - Silk cocoons are composed of fiber proteins (fibroins) and adhesive glue proteins
      (sericins), which provide a physical barrier to protect the inside pupa.
      Moreover, other proteins were identified in the cocoon silk, many of which are
      immune related proteins. In this study, we extracted proteins from the silkworm
      cocoon by Tris-HCl buffer (pH7.5), and found that they had a strong inhibitory
      activity against fungal proteases and they had higher abundance in the outer
      cocoon layers than in the inner cocoon layers. Moreover, we found that extracted
      cocoon proteins can inhibit the germination of Beauveria bassiana spores.
      Consistent with the distribution of protease inhibitors, we found that proteins
      from the outer cocoon layers showed better inhibitory effects against B. bassiana
      spores than proteins from the inner layers. Liquid chromatography-tandem mass
      spectrometry was used to reveal the extracted components in the scaffold silk,
      the outermost cocoon layer. A total of 129 proteins were identified, 30 of which
      were annotated as protease inhibitors. Protease inhibitors accounted for 89.1% in
      abundance among extracted proteins. These protease inhibitors have many
      intramolecular disulfide bonds to maintain their stable structure, and remained
      active after being boiled. This study added a new understanding to the
      antimicrobial function of the cocoon. 

PMID- 27032087
TI  - Mapping Muscles Activation to Force Perception during Unloading.
AB  - It has been largely proved that while judging a force humans mainly rely on the
      motor commands produced to interact with that force (i.e., sense of effort).
      Despite of a large bulk of previous investigations interested in understanding
      the contributions of the descending and ascending signals in force perception,
      very few attempts have been made to link a measure of neural output (i.e., EMG)
      to the psychophysical performance. Indeed, the amount of correlation between EMG
      activity and perceptual decisions can be interpreted as an estimate of the
      contribution of central signals involved in the sensation of force. In this study
      we investigated this correlation by measuring the muscular activity of eight arm
      muscles while participants performed a quasi-isometric force detection task. Here
      we showed a method to quantitatively describe muscular activity ("muscle-metric
      function") that was directly comparable to the description of the participants'
      psychophysical decisions about the stimulus force. We observed that under our
      experimental conditions, muscle-metric absolute thresholds and the shape of the
      muscle-metric curves were closely related to those provided by the psychophysics.
      In fact a global measure of the muscles considered was able to predict
      approximately 60% of the perceptual decisions total variance. Moreover the inter
      subjects differences in psychophysical sensitivity showed high correlation with
      both participants' muscles sensitivity and participants' joint torques. Overall,
      our findings gave insights into both the role played by the corticospinal motor
      commands while performing a force detection task and the influence of the
      gravitational muscular torque on the estimation of vertical forces. 

PMID- 27032086
TI  - Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of
      Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals.
AB  - OBJECTIVE: In the era of bare metal stents (BMSs), alloys have been considered to
      be better materials for stent design than stainless steel. In the era of
      biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of
      BP-DESs with different metal platforms (stainless steel or alloys) have not yet
      been reported, although their polymers are eventually absorbed, and only the
      metal platforms remain in the body. This study sought to determine the clinical
      safety and efficacy of BP-DESs with different platforms compared with other
      stents (other DESs and BMSs). METHODS: PubMed, Embase and Clinical Trials.gov
      were searched for randomized controlled trials (RCTs) that compared BP-DESs with
      other stents. After performing pooled analysis of BP-DESs and other stents, we
      performed a subgroup analysis using two classification methods: stent platform
      and follow-up time. The study characteristics, patient characteristics and
      clinical outcomes were abstracted. RESULTS: Forty RCTs (49 studies) comprising
      34,850 patients were included. Biodegradable polymer stainless drug-eluting
      stents (BP-stainless DESs) were superior to the other stents [mainly stainless
      drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis
      (ST) (OR [95% CI] = 0.76[0.61-0.95], p = 0.02), long-term definite/probable ST
      (OR [95% CI] = 0.73[0.57-0.94], p = 0.01), very late definite/probable ST (OR
      [95% CI] = 0.56[0.33-0.93], p = 0.03) and long-term definite ST. BP-stainless
      DESs had lower rates of pooled, mid-term and long-term target vessel
      revascularization (TVR) and target lesion revascularization (TLR) than the other
      stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with
      lower rates of long-term death than other stainless DESs and lower rates of mid
      term myocardial infarction than BMSs. However, only the mid-term and long-term
      TVR rates were superior in BP-alloy DESs compared with the other stents.
      CONCLUSION: Our results indirectly suggest that BP-stainless DESs may offer more
      benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs
      comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is
      better.

PMID- 27032089
TI  - Alternatives to the use of animals in research, education and testing.

PMID- 27032088
TI  - Making big sense from big data in toxicology by read-across.
AB  - Modern information technologies have made big data available in safety sciences,
      i.e., extremely large data sets that may be analyzed only computationally to
      reveal patterns, trends and associations. This happens by (1) compilation of
      large sets of existing data, e.g., as a result of the European REACH regulation,
      (2) the use of omics technologies and (3) systematic robotized testing in a high
      throughput manner. All three approaches and some other high-content technologies
      leave us with big data--the challenge is now to make big sense of these data.
      Read-across, i.e., the local similarity-based intrapolation of properties, is
      gaining momentum with increasing data availability and consensus on how to
      process and report it. It is predominantly applied to in vivo test data as a gap
      filling approach, but can similarly complement other incomplete datasets. Big
      data are first of all repositories for finding similar substances and ensure that
      the available data is fully exploited. High-content and high-throughput
      approaches similarly require focusing on clusters, in this case formed by
      underlying mechanisms such as pathways of toxicity. The closely connected
      properties, i.e., structural and biological similarity, create the confidence
      needed for predictions of toxic properties. Here, a new web-based tool under
      development called REACH-across, which aims to support and automate structure
      based read-across, is presented among others.

PMID- 27032090
TI  - 3Rs in Education.

PMID- 27032091
TI  - Toxicology is IN: in silico, in vitro, integrated testing strategy.

PMID- 27032092
TI  - Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal
      Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials.
AB  - OBJECTIVE: The addition of lipophilic opioids to local anesthetics for spinal
      anesthesia has become a widely used strategy for cesarean anesthesia. A meta
      analysis to quantify the benefits and risks of combining sufentanil with
      bupivacaine for patients undergoing cesarean delivery was conducted. METHODS: A
      comprehensive literature search without language or date limitation was performed
      to identify clinical trials that compared the addition of sufentanil to
      bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients
      choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity
      of the data. Data from each trial were combined using relative ratios (RRs) for
      dichotomous data or weighted mean differences (WMDs) for continuous data and
      corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity
      analysis was conducted by removing one study a time to assess the quality and
      consistency of the results. Begg's funnel plots and Egger's linear regression
      test were used to detect any publication bias. RESULTS: This study included 9
      trials containing 578 patients in the final meta-analysis. Sufentanil addition
      provided a better analgesia quality with less breakthrough pain during surgery
      than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block
      onset time was shorter and first analgesic request time was longer in sufentanil
      added group compared with the bupivacaine-alone group (WMD = -1.0 min, 95% CI 
      1.5 to -0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192,
      respectively). There was no significant difference in the risk of hypotension and
      vomiting between these two groups. But pruritus was more frequentely reported in
      the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001).
      CONCLUSION: Bupivacaine and sufentanil combination is superior to that of
      bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia
      quality. Women receiving the combined two drugs had less breakthrough pain,
      shorter sensory block onset time, and longer first analgesic request time.
      However, the addition of sufentanil to bupivacaine increased the incidence of
      pruritus.

PMID- 27032094
TI  - Laboratory Evaluation of the Alere q Point-of-Care System for Early Infant HIV
      Diagnosis.
AB  - INTRODUCTION: Early infant diagnosis (EID) and prompt linkage to care are
      critical to minimise the high morbidity and mortality associated with infant HIV
      infection. Attrition in the "EID cascade" is common; however, point-of-care (POC)
      EID assays with same-day result could facilitate prompt linkage of HIV-infected
      infant to treatment. Despite a number of POC EID assays in development, few have
      been independently evaluated and data on new technologies are urgently needed to
      inform policy. METHODS: We compared Alere q 1/2 Detect POC system laboratory test
      characteristics with the local standard of care (SOC), Roche CAP/CTM HIV-1
      qualitative PCR in an independent laboratory-based evaluation in Cape Town, South
      Africa. Routinely EID samples collected between November 2013 and September 2014
      were each tested by both SOC and POC systems. Repeat testing was done to
      troubleshoot any discrepancy between POC and SOC results. RESULTS: Overall, 1098
      children with a median age of 47 days (IQR, 42-117) were included. Birth PCR (age
      <7 days) comprised of 8% (n = 92) tests while 56% (n = 620) of children tested as
      part of routine EID (ages 6-14 weeks). In the overall direct comparison, Alere q
      Detect achieved sensitivity of 95.5% (95% CI, 91.7-97.9%) and a specificity of
      99.8% (95% CI, 99.1-100%). Following repeat testing of discordant samples and
      exclusion of any inconclusive results, the POC assay sensitivity and specificity
      were 96.9% (95% CI 93.4-98.9%) and 100% (lower 95% CI 98%) respectively. Among
      birth PCR tests the POC assay had slightly lower sensitivity (93.3% vs 96.5% in
      routine EID) and higher assay error rate (10% vs 5% in samples of older children,
      p = 0.04). CONCLUSION: Our results indicate this POC assay performs well for EID
      in the laboratory. The high specificity and thus high positive predictive value
      would suggest a positive POC result may be adequate for immediate infant ART
      initiation. While POC testing for EID may have particular utility for birth
      testing at delivery facilities, the lower sensitivity and error rate requires
      further attention, as does field implementation of POC EID technologies in other
      clinical care settings.

PMID- 27032093
TI  - Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses
      as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.
AB  - The poliovirus vaccine field is moving towards novel vaccination strategies.
      Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional
      Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the
      virulent poliovirus strains currently used for cIPV with attenuated strains is
      preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains
      by serial passage at low temperature and subsequent genetic engineering, which
      contain the capsid sequences of cIPV strains combined with a set of mutations
      identified during cold-adaptation. These viruses displayed a highly temperature
      sensitive phenotype with no signs of productive infection at 37 degrees C as
      visualized by electron microscopy. Furthermore, decreases in infectious titers,
      viral RNA, and protein levels were measured during infection at 37 degrees C,
      suggesting a block in the viral replication cycle at RNA replication, protein
      translation, or earlier. However, at 30 degrees C, they could be propagated to
      high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We
      identified 14 mutations in the IRES and non-structural regions, which in
      combination induced the temperature sensitive phenotype, also when transferred to
      the genomes of other wild-type and attenuated polioviruses. The temperature
      sensitivity translated to complete absence of neurovirulence in CD155 transgenic
      mice. Attenuation was also confirmed after extended in vitro passage at small
      scale using conditions (MOI, cell density, temperature) anticipated for vaccine
      production. The inability of CAVA strains to replicate at 37 degrees C makes
      reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these
      strains can be considered safe for the manufacture of IPV. The CAVA strains were
      immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing
      antibody titers in a dose-dependent manner in response to D-antigen doses used
      for cIPV. In combination with the highly productive PER.C6 cell culture platform,
      the stably attenuated CAVA strains may serve as an attractive low-cost and
      (bio)safe option for the production of a novel next generation IPV. 

PMID- 27032095
TI  - Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A
      Time-Trend Analysis.
AB  - BACKGROUND: Following Food and Drug Administration (FDA) approval, many drugs are
      prescribed for non-FDA-approved ("off-label") uses. If substantial evidence
      supports the efficacy and safety of off-label indications, manufacturers can
      pursue formal FDA approval through supplemental new drug applications (sNDAs). We
      evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic
      drugs on prescribing of these products in children. METHODS: Retrospective,
      segmented time-series analysis using new prescription claims during 2003-2012 for
      three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved
      the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but
      did not approve the sNDA for pediatric use of ziprasidone. RESULTS: During the
      months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine
      decreased for both children and adults. After FDA approval, the increase in
      prescribing trends was similar for both age groups (P = 0.47 for schizophrenia
      and bipolar disorder; P = 0.37 for other indications). Comparable decreases in
      use of quetiapine were observed between pediatrics and adults following FDA
      approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone
      decreased similarly for pediatric and adult patients after FDA non-approval of
      its pediatric sNDA (P = 0.61; P = 0.79). CONCLUSIONS: The FDA's sNDA
      determinations relating to use of antipsychotics in children did not result in
      changes in use that favored the approved sNDAs and disfavored the unapproved
      sNDA. Improved communication may help translate the agency's expert judgments to
      clinical practice.

PMID- 27032096
TI  - Whole-genome-based phylogeny supports the objections against the reclassification
      of Eubacterium rectale to Agathobacter rectalis.

PMID- 27032098
TI  - Dry Eye Disease in Patients with Functioning Filtering Blebs after
      Trabeculectomy.
AB  - PURPOSE: The aim of this study was to analyze dry eye disease (DED) in patients
      with functioning filtering blebs and to explore the relationship between the
      morphology of filtering blebs and ocular surface instability. METHODS: This was a
      cross-sectional, case-comparison study. Seventy glaucomatous patients (70 eyes)
      with functioning blebs who had undergone trabeculectomy more than 6 months prior
      (study group) and 35 control subjects (35 eyes) (control group) were included.
      All subjects completed an ocular symptom questionnaire that referred to the
      Shihpai Eye Study. Evaluation of meibomian gland obstruction, a tear film break
      up time test (TFBUT), fluorescein corneal staining and a Schirmer's tear test
      were then performed. Filtering bleb morphology was analyzed using Wuerzburg bleb
      classification scoring criteria in the study group. The presence of DED was
      defined as the concomitant presence of TFBUT <10 seconds and the presence of
      superficial punctate keratitis. RESULTS: The patients with functioning blebs
      presented higher corneal staining scores (P = 0.012) and lower TFBUT values (P =
      0.043) than the control group. DED was present in 28/70 patients in the study
      group and 6/35 patients in the control group (P = 0.018). More patients in the
      study group complained of dryness (P = 0.001), a gritty or sandy sensation (P <
      0.001) and redness (P = 0.048). In the study group, the patients with DED were
      significantly different from the patients without DED in both TFBUT (P < 0.001)
      and corneal staining (P < 0.001). More patients in the DED group were likely to
      report dryness (P = 0.013) and watery or teary eyes (P = 0.012). The differences
      in meibomian gland obstruction scores between the study and the control group,
      the DED and the non-DED group were not significant (P = 0.105 and P = 0.077,
      respectively). The values for microcysts and bleb heights were significantly
      higher in the DED group (P = 0.040 and P = 0.011, respectively). A Spearman's
      rank correlation showed that microcysts were positively correlated with corneal
      staining (r = 0.270, P = 0.024). Bleb height was negatively correlated with TFBUT
      (r = -0.299, P = 0.012) and positively correlated with corneal staining (r =
      0.275, P = 0.021). The relationships between DED and microcysts and between DED
      and bleb height were significant (r = 0.247, P = 0.039 and r = 0.307, P = 0.010,
      respectively). CONCLUSION: DED is relatively common in patients with functioning
      filtering blebs following trabeculectomy. In DED patients, dryness and watery are
      common symptoms. Microcysts and bleb height are related to ocular surface
      instability and DED.

PMID- 27032099
TI  - Novel bat adenoviruses with an extremely large E3 gene.
AB  - Bats carry diverse RNA viruses, some of which are responsible for human diseases.
      Compared to bat-borne RNA viruses, relatively little information is known
      regarding bat-borne DNA viruses. In this study, we isolated and characterized
      three novel bat adenoviruses (BtAdV WIV9-11) from Rhinolophus sinicus. Their
      genomes, which are highly similar to each other but distinct from those of
      previously sequenced adenoviruses (AdVs), are 37 545, 37 566 and 38 073 bp in
      size, respectively. An unusually large E3 gene was identified in their genomes.
      Phylogenetic and taxonomic analyses suggested that these isolates represent a
      distinct species of the genus Mastadenovirus. Cell susceptibility assays revealed
      a broad cell tropism for these isolates, indicating that they have a potentially
      wide host range. Our results expand the understanding of genetic diversity of bat
      AdVs.

PMID- 27032097
TI  - Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in
      Mozambique and Zambia.
AB  - BACKGROUND: Few data on the virological determinants of hepatitis B virus (HBV)
      infection are available from southern Africa. METHODS: We enrolled consecutive
      HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban
      clinics in Zambia and four rural clinics in Northern Mozambique between May 2013
      and August 2014. HBsAg screening was performed using the Determine(r) rapid test.
      Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive
      patients. Risk factors for HBV infection were evaluated using Chi-square and Mann
      Whitney tests and associations between baseline characteristics and high level
      HBV replication explored in multivariable logistic regression. RESULTS: Seventy
      eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]:
      6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive.
      HBsAg-positive individuals were less likely to be female compared to HBsAg
      negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive
      patients with an available measurement, median HBV viral load was 13,645 IU/mL
      (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values
      (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST
      compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male
      sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below
      200/MUl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1
      (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance
      to lamivudine and/or entecavir. CONCLUSION: One half of HBsAg-positive patients
      demonstrated high HBV viremia, supporting the early initiation of tenofovir
      containing ART in HIV/HBV-coinfected adults.

PMID- 27032100
TI  - Genetic Diversity and Hybridisation between Native and Introduced Salmonidae
      Fishes in a Swedish Alpine Lake.
AB  - Understanding the processes underlying diversification can aid in formulating
      appropriate conservation management plans that help maintain the evolutionary
      potential of taxa, particularly under human-induced activities and climate
      change. Here we assessed the microsatellite genetic diversity and structure of
      three salmonid species, two native (Arctic charr, Salvelinus alpinus and brown
      trout, Salmo trutta) and one introduced (brook charr, Salvelinus fontinalis),
      from an alpine lake in sub-arctic Sweden, Lake Ann. The genetic diversity of the
      three species was similar and sufficiently high from a conservation genetics
      perspective: corrected total heterozygosity, H'T = 0.54, 0.66, 0.60 and allelic
      richness, AR = 4.93, 5.53 and 5.26 for Arctic charr, brown trout and brook charr,
      respectively. There were indications of elevated inbreeding coefficients in brown
      trout (GIS = 0.144) and brook charr (GIS = 0.129) although sibling relationships
      were likely a confounding factor, as a high proportion of siblings were observed
      in all species within and among sampling locations. Overall genetic structure
      differed between species, Fst = 0.01, 0.02 and 0.04 in Arctic charr, brown trout
      and brook charr respectively, and there was differentiation at only a few
      specific locations. There was clear evidence of hybridisation between the native
      Arctic charr and the introduced brook charr, with 6% of individuals being
      hybrids, all of which were sampled in tributary streams. The ecological and
      evolutionary consequences of the observed hybridisation are priorities for
      further research and the conservation of the evolutionary potential of native
      salmonid species. 

PMID- 27032102
TI  - An Ultrastructural and Immunohistochemical Analysis of the Outer Plexiform Layer
      of the Retina of the European Silver Eel (Anguilla anguilla L).
AB  - Here we studied the ultrastructural organization of the outer retina of the
      European silver eel, a highly valued commercial fish species. The retina of the
      European eel has an organization very similar to most vertebrates. It contains
      both rod and cone photoreceptors. Rods are abundantly present and immunoreactive
      for rhodopsin. Cones are sparsely present and only show immunoreactivity for M
      opsin and not for L-, S- or UV-cone opsins. As in all other vertebrate retinas,
      Muller cells span the width of the retina. OFF-bipolar cells express the
      ionotropic glutamate receptor GluR4 and ON-bipolar cells, as identified by their
      PKCalpha immunoreactivity, express the metabotropic receptor mGluR6. Both the ON-
      and the OFF-bipolar cell dendrites innervate the cone pedicle and rod spherule.
      Horizontal cells are surrounded by punctate Cx53.8 immunoreactivity indicating
      that the horizontal cells are strongly electrically coupled by gap-junctions.
      Connexin-hemichannels were found at the tips of the horizontal cell dendrites
      invaginating the photoreceptor synapse. Such hemichannels are implicated in the
      feedback pathway from horizontal cells to cones. Finally, horizontal cells are
      surrounded by tyrosine hydroxylase immunoreactivity, illustrating a strong
      dopaminergic input from interplexiform cells. 

PMID- 27032104
TI  - Male Extragonadal Germ Cell Tumors of the Adult.
AB  - Male extragonadal germ cell tumors (EGCTs) are characterized by a malignant
      transformation of germ cells without the presence of a gonadal primary tumor.
      EGCTs represent up to 5% of all germ cell tumors (GCTs) with an incidence around
      1/1,000,000. It is assumed that EGCTs either derive from a malignant
      transformation of germ cells that were misdirected during embryogenesis, or from
      germ cells that have spread throughout the body during embryogenesis to fulfil
      different roles in immunological processes or distinct organ functions. EGCTs are
      mainly localized along the median axis, especially in the mediastinum and in the
      retroperitoneum. Regarding histology, they have the same subtypes as gonadal GCTs
      (seminomas and non-seminomas). EGCTs are normally diagnosed in advanced stages
      due to tumor-associated symptoms or as incidental finding during routine
      diagnostic or therapeutic procedures. An integral part of EGCT treatment is
      cisplatinum-based chemotherapy: residual tumor resection is only indicated for
      non-seminomatous EGCTs. The prognosis of malignant retroperitoneal EGCTs depends
      on tumor localization and histology. The 5-year overall survival ranges from 40%
      to 90% and is more favorable for retroperitoneal or seminomatous tumors than for
      mediastinal non-seminomatous tumors. Mature teratomas of mediastinal EGCTs are
      benign and are only treated by surgical resection. 

PMID- 27032101
TI  - Estrogen Receptor Expression Is Associated with DNA Repair Capacity in Breast
      Cancer.
AB  - Estrogen-receptor-positive (ER+) tumors employ complex signaling that engages in
      crosstalk with multiple pathways through genomic and non-genomic regulation. A
      greater understanding of these pathways is important for developing improved
      biomarkers that can better determine treatment choices, risk of recurrence and
      cancer progression. Deficiencies in DNA repair capacity (DRC) is a hallmark of
      breast cancer (BC); therefore, in this work we tested whether ER signaling
      influences DRC. We analyzed the association between ER positivity (% receptor
      activation) and DRC in 270 BC patients, then further stratified our analysis by
      HER2 receptor status. Our results show that among HER2 negative, the likelihood
      of having low DRC values among ER- women is 1.92 (95% CI: 1.03, 3.57) times the
      likelihood of having low DRC values among ER+ women, even adjusting for different
      potential confounders (p<0.05); however, a contrary pattern was observed among
      HER2 positives women. In conclusion, there is an association between DRC levels
      and ER status, and this association is modified by HER2 receptor status. Adding a
      DNA repair capacity test to hormone receptor testing may provide new information
      on defective DNA repair phenotypes, which could better stratify BC patients who
      have ER+ tumors. ER+/HER2- tumors are heterogeneous, incompletely defined, and
      clinically challenging to treat; the addition of a DRC test could better
      characterize and classify these patients as well as help clinicians select
      optimal therapies, which could improve outcomes and reduce recurrences. 

PMID- 27032103
TI  - Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial
      Remodeling.
AB  - AIMS: Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms
      alpha and beta) have impaired expansive arterial remodeling due to diminished
      expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a
      target in cardiovascular disease prompted the investigation of the redundancy of
      IL-1alpha and IL-1beta in the induction of MMP-3 and other matrix-remodeling
      enzymes in human cells. METHODS AND RESULTS: Human primary vascular smooth muscle
      cells (VSMCs) and carotid endarterectomy specimens were stimulated with equimolar
      concentrations of IL-1alpha or IL-1beta and analyzed protease expression by
      immunoblot and ELISA. Either IL-1alpha or IL-1beta increased the expression of
      pro-MMP-3 in VSMCs, facilitated VSMC migration through Matrigel, and induced MMP
      3 production in specimens from atheromatous plaques. VSMCs also secreted MMP-1
      and Cathepsin S (CatS) upon stimulation with IL-1alpha or IL-1beta. IL-1 isoforms
      similarly increased MMP-1 and MMP-9 expression in carotid endarterectomy
      specimens. We examined the expression of MMP-3 and IL-1 isoforms by
      immunostaining of carotid atheromata, calculated the % positive areas, and tested
      associations by linear regression. MMP-3 colocalized with IL-1 isoforms in
      atheromata. MMP-3+ area in plaques positively associated with IL-1alpha+ (R2 =
      0.61, P<0.001) and with IL-1beta + areas (R2 = 0.68, P<0.001). MMP-3+ area within
      atheroma also associated with CD68+ area, but not with alpha-smooth muscle actin
      area. CONCLUSIONS: Either IL-1alpha or IL-1beta can induce the expression of
      enzymes implicated in remodeling of the arterial extracellular matrix, and
      facilitate human VSMC migration in vitro. Human atheromata contain both IL-1
      isoforms in association with immunoreactive MMP-3. This redundancy of IL-1
      isoforms suggests that selective blocking of one IL-1 isoform should not impair
      expansive arterial remodeling, a finding with important clinical implications for
      therapeutic targeting of IL-1 in atherosclerosis.

PMID- 27032106
TI  - Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide
      Fragments of the Gut-Derived Hormone Xenin.
AB  - Xenin is a peptide that is co-secreted with the incretin hormone, glucose
      dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response
      to feeding. Studies demonstrate that xenin has appetite suppressive effects and
      modulates glucose-induced insulin secretion. The present study was undertaken to
      determine the bioactivity and antidiabetic properties of two C-terminal fragment
      xenin peptides, namely xenin 18-25 and xenin 18-25 Gln. In BRIN-BD11 cells, both
      xenin fragment peptides concentration-dependently stimulated insulin secretion,
      with similar efficacy as the parent peptide. Neither fragment peptide had any
      effect on acute feeding behaviour at elevated doses of 500 nmol/kg bw. When
      administered together with glucose to normal mice at 25 nmol/kg bw, the overall
      insulin secretory effect was significantly enhanced in both xenin 18-25 and xenin
      18-25 Gln treated mice, with better moderation of blood glucose levels. Twice
      daily administration of xenin 18-25 or xenin 18-25 Gln for 21 days in high fat
      fed mice did not affect energy intake, body weight, circulating blood glucose or
      body fat stores. However, circulating plasma insulin concentrations had a
      tendency to be elevated, particularly in xenin 18-25 Gln mice. Both treatment
      regimens significantly improved insulin sensitivity by the end of the treatment
      period. In addition, sustained treatment with xenin 18-25 Gln significantly
      reduced the overall glycaemic excursion and augmented the insulinotropic response
      to an exogenous glucose challenge on day 21. In harmony with this, GIP-mediated
      glucose-lowering and insulin-releasing effects were substantially improved by
      twice daily xenin 18-25 Gln treatment. Overall, these data provide evidence that
      C-terminal octapeptide fragments of xenin, such as xenin 18-25 Gln, have
      potential therapeutic utility for type 2 diabetes. 

PMID- 27032105
TI  - The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide
      Investigation of Key Phases in Disease Evolution and New Treatment Options.
AB  - The mechanisms leading to disability and the long-term efficacy and safety of
      disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed
      at building a prospective cohort of MS patients with standardized collection of
      demographic, clinical, MRI data and body fluids that can be used to develop
      prognostic indicators and biomarkers of disease evolution and therapeutic
      response. The Swiss MS Cohort (SMSC) is a prospective observational study
      performed across seven Swiss MS centers including patients with MS, clinically
      isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis
      optica. Neurological and radiological assessments and biological samples are
      collected every 6-12 months. We recruited 872 patients (clinically isolated
      syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS
      [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July
      2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274
      serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain
      MRI scans. 158 relapses occurred and expanded disability status scale (EDSS)
      scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS
      patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable
      DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy
      and safety and will serve as a comprehensive infrastructure available for nested
      research projects. 

PMID- 27032107
TI  - Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung
      Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase
      II Study in Caucasian Patients (FIELT).
AB  - INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition
      is the preferred first-line treatment of advanced adenocarcinoma of the lung that
      harbors EGFR activating tyrosine kinase domain mutations. Most data available
      pertain to Asian populations in which such mutations are more prevalent. We
      report on the long-term results of first-line treatment with erlotinib in
      Caucasian patients with advanced adenocarcinoma of the lung that have a somatic
      EGFR mutation in their tumor. METHODS: Multicenter academic prospective phase II
      study with erlotinib in patients with an activating EGFR tyrosine kinase (TK)
      domain somatic mutation (any exon encoding the kinase domain) in the tumor and no
      prior treatment for their advanced disease. RESULTS: Phenotypic preselecting of
      229 patients led to a high EGFR mutation detection rate of 24% of which 46
      patients were included in the phase II study. With a progression free survival
      (PFS) of 81% at three months the study met its primary endpoint for presumed
      superiority over chemotherapy. With an overall median PFS of 11 months and a
      median overall survival (OS) of 23 months, the results compare favorably with
      results obtained in randomized studies using TKI in first line in EGFR mutation
      positive adenocarcinoma of the lung. CONCLUSION: The present study reinforces the
      use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice
      for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The
      mutation rate in preselected Caucasian patients is higher than previously
      reported. Issues relevant for clinical practice are discussed. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00339586.

PMID- 27032108
TI  - Classifying Response Correctness across Different Task Sets: A Machine Learning
      Approach.
AB  - Erroneous behavior usually elicits a distinct pattern in neural waveforms. In
      particular, inspection of the concurrent recorded electroencephalograms (EEG)
      typically reveals a negative potential at fronto-central electrodes shortly
      following a response error (Ne or ERN) as well as an error-awareness-related
      positivity (Pe). Seemingly, the brain signal contains information about the
      occurrence of an error. Assuming a general error evaluation system, the question
      arises whether this information can be utilized in order to classify behavioral
      performance within or even across different cognitive tasks. In the present
      study, a machine learning approach was employed to investigate the outlined
      issue. Ne as well as Pe were extracted from the single-trial EEG signals of
      participants conducting a flanker and a mental rotation task and subjected to a
      machine learning classification scheme (via a support vector machine, SVM).
      Overall, individual performance in the flanker task was classified more
      accurately, with accuracy rates of above 85%. Most importantly, it was even
      feasible to classify responses across both tasks. In particular, an SVM trained
      on the flanker task could identify erroneous behavior with almost 70% accuracy in
      the EEG data recorded during the rotation task, and vice versa. Summed up, we
      replicate that the response-related EEG signal can be used to identify erroneous
      behavior within a particular task. Going beyond this, it was possible to classify
      response types across functionally different tasks. Therefore, the outlined
      methodological approach appears promising with respect to future applications. 

PMID- 27032110
TI  - Estimating the rates of deaths by suicide among adults who attempt suicide in the
      United States.
AB  - BACKGROUND: In 2012, over 1.3 million U.S. adults reported that they attempted
      suicide in the past year, and 39,426 adults died by suicide. This study estimated
      national suicide case fatality rates among adult suicide attempters (fatal and
      nonfatal cases) and examined how they varied by sociodemographic characteristics.
      METHODS: We pooled data on deaths by suicide (n = 147,427, fatal cases in the
      U.S.) from the 2008-2011 U S. mortality files and data on suicide attempters who
      survived (n = 2000 nonfatal cases) from the 2008-2012 National Surveys on Drug
      Use and Health. Descriptive analyses and multivariable logistic regression models
      were applied. RESULTS: Among adult suicide attempters in the U.S., the overall 12
      month suicide case fatality rate was 3.2% (95% confidence interval (CI) = 2.9%
      3.5%). It varied significantly by sociodemographic factors. For those aged 45 or
      older, the adjusted suicide case fatality rate was higher among men (7.6%) than
      among women (2.6%) (suicide case fatality rate ratio (SCFRR) = 3.0, 95% CI = 1.83
      4.79), was higher among non-Hispanic whites (7.9%) than among non-white
      minorities (0.8-2.5%) (SCFRRs = 3.2-9.9), and was higher among those with less
      than high school education (16.0%) than among college graduates (1.8%) (SCFRR =
      8.8, 95% CI = 3.83-20.16). Across male and female attempters, being aged 45 or
      older and non-Hispanic white and having less than secondary school were at a
      higher risk for death by suicide. CONCLUSIONS: Focusing on these demographic
      characteristics can help identify suicide attempters at higher risk for death by
      suicide, inform clinical assessments, and improve suicide prevention and
      intervention efforts by increasing high-risk suicide attempters' access to mental
      health treatment.

PMID- 27032109
TI  - Prolonged Nightly Fasting and Breast Cancer Prognosis.
AB  - IMPORTANCE: Rodent studies demonstrate that prolonged fasting during the sleep
      phase positively influences carcinogenesis and metabolic processes that are
      putatively associated with risk and prognosis of breast cancer. To our knowledge,
      no studies in humans have examined nightly fasting duration and cancer outcomes.
      OBJECTIVE: To investigate whether duration of nightly fasting predicted
      recurrence and mortality among women with early-stage breast cancer and, if so,
      whether it was associated with risk factors for poor outcomes, including
      glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein),
      obesity, and sleep. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from
      2413 women with breast cancer but without diabetes mellitus who were aged 27 to
      70 years at diagnosis and participated in the prospective Women's Healthy Eating
      and Living study between March 1, 1995, and May 3, 2007. Data analysis was
      conducted from May 18 to October 5, 2015. EXPOSURES: Nightly fasting duration was
      estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4.
      MAIN OUTCOMES AND MEASURES: Clinical outcomes were invasive breast cancer
      recurrence and new primary breast tumors during a mean of 7.3 years of study
      follow-up as well as death from breast cancer or any cause during a mean of 11.4
      years of surveillance. Baseline sleep duration was self-reported, and archived
      blood samples were used to assess concentrations of hemoglobin A1c and C-reactive
      protein. RESULTS: The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years)
      reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated
      measures Cox proportional hazards regression models, fasting less than 13 hours
      per night (lower 2 tertiles of nightly fasting distribution) was associated with
      an increase in the risk of breast cancer recurrence compared with fasting 13 or
      more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting
      less than 13 hours was not associated with a statistically significant higher
      risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a
      statistically significant higher risk of all-cause mortality (hazard ratio, 1.22;
      95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour
      increase in the nightly fasting duration was associated with significantly lower
      hemoglobin A1c levels (beta = -0.37; 95% CI, -0.72 to -0.01) and a longer
      duration of nighttime sleep (beta = 0.20; 95% CI, 0.14-0.26). CONCLUSIONS AND
      RELEVANCE: Prolonging the length of the nightly fasting interval may be a simple,
      nonpharmacologic strategy for reducing the risk of breast cancer recurrence.
      Improvements in glucoregulation and sleep may be mechanisms linking nightly
      fasting with breast cancer prognosis.

PMID- 27032111
TI  - Optimal vitamin D plasma levels are associated with lower bacterial DNA
      translocation in HIV/hepatitis c virus coinfected patients.
AB  - OBJECTIVE: Vitamin D has been linked to the immune response modulation and the
      integrity of the intestinal mucosal barrier. Therefore, vitamin D might be
      involved in bacterial translocation related to HIV infection. Our major aim was
      to analyze the association between plasma levels of 25-hydroxy-vitamin D
      [25(OH)D] and bacterial 16S ribosomal DNA (bactDNA) in 120 HIV/hepatitis c virus
      (HCV) coinfected patients. DESIGN: Cross-sectional study. METHODS: Plasma 25(OH)D
      levels were quantified by enzyme immunoassay. The vitamin D status was defined as
      deficient (<25 nmol/l), insufficient (25-74 nmol/l), and optimal (>=75 nmol/l)
      plasma levels. Plasma bactDNA levels were measured by quantitative real-time PCR.
      For bactDNA levels the cutoffs used were as follows: low [<p25th (46
      copies/MUl)], moderate [p25th to p50th (78 copies/MUl)], high [p50th to p75th
      (159 copies/MUl)], and very high (>p75th). RESULTS: Eighteen (15%) patients had
      25(OH)D deficiency, 93 (77.5%) had insufficiency and nine (7.5%) had 25(OH)D
      optimal values. The bactDNA levels were lower in patients with 25(OH)D at least
      75 nmol/l [37 copies/MUl] than in patients with 25(OH)D insufficiency [84.2
      copies/MUl; P = 0.042]. Conversely, low bactDNA levels (<p25th) were found in
      66.7% of patients with 25(OH)D optimal levels, whereas bactDNA levels above p25th
      were found only in 11.1% of them (P = 0.029). The plasma 25(OH)D not less than 75
      nmol/l was associated with low bactDNA levels (<p25th) [adjusted OR = 8.13 (95%
      confidence interval = 1.82; 36.67); P = 0.006)]. The patients with optimal
      vitamin D status [25(OH)D >=75 nmol/l] had lower plasma levels of CCL7 (P =
      0.047) and basic fibroblast growth factor (P = 0.042). CONCLUSION: The optimal
      vitamin D status was associated with low bacterial translocation and inflammation
      in HIV/HCV coinfected patients.

PMID- 27032113
TI  - COST IMPLICATIONS OF UNNECESSARY   COAGULATION SCREENS IN SURGICAL   PATIENTS--A
      MULTI-CENTRE STUDY.

PMID- 27032112
TI  - Transcriptome Analysis of Spartina pectinata in Response to Freezing Stress.
AB  - Prairie cordgrass (Spartina pectinata), a perennial C4 grass native to the North
      American prairie, has several distinctive characteristics that potentially make
      it a model crop for production in stressful environments. However, little is
      known about the transcriptome dynamics of prairie cordgrass despite its unique
      freezing stress tolerance. Therefore, the purpose of this work was to explore the
      transcriptome dynamics of prairie cordgrass in response to freezing stress at -5
      degrees C for 5 min and 30 min. We used a RNA-sequencing method to assemble the
      S. pectinata leaf transcriptome and performed gene-expression profiling of the
      transcripts under freezing treatment. Six differentially expressed gene (DEG)
      groups were categorized from the profiling. In addition, two major consecutive
      orders of gene expression were observed in response to freezing; the first being
      the acute up-regulation of genes involved in plasma membrane modification,
      calcium-mediated signaling, proteasome-related proteins, and transcription
      regulators (e.g., MYB and WRKY). The follow-up and second response was of genes
      involved in encoding the putative anti-freezing protein and the previously known
      DNA and cell-damage-repair proteins. Moreover, we identified the genes involved
      in epigenetic regulation and circadian-clock expression. Our results indicate
      that freezing response in S. pectinata reflects dynamic changes in rapid-time
      duration, as well as in metabolic, transcriptional, post-translational, and
      epigenetic regulation. 

PMID- 27032114
TI  - POST OPERATIVE RECOVERY TIME: AN   INTERNATIONAL SURVEY OF ENT SURGEONS   ADVICE.

PMID- 27032115
TI  - RIVAROXABAN ASSAY:   A SINGLE CENTRE EXPERIENCE MEASURING   RIVAROXABAN LEVELS
      WITH A SPECIFIC ANTI   XA ASSAY AND THE EFFECT ON THE STANDARD   COAGULATION
      SCREEN.

PMID- 27032116
TI  - INFLUENCE OF ETHNIC ORIGIN ON VZV SEROPREVALENCE IN WOMEN OF CHILD-BEARING AGE.

PMID- 27032117
TI  - CHEMICAL BURN FROM CONTACT WITH   SCRUBBING SOLUTION.

PMID- 27032118
TI  - MESOTHELIAL INCLUSIONS MASQUERADING AS   METASTATIC CARCINOMA.

PMID- 27032119
TI  - John Leonard Young, MD, MTh, CSC:   Philosopher, Priest, and Forensic  
      Psychiatrist.

PMID- 27032120
TI  - [Study on Pb-Blood and electrocardiogram changes of the population occupationally
      exposed to paint].

PMID- 27032121
TI  - [The trends on secular growth among Ha' ni ethnicity children and adolescents in
      Hani-Yi autonomous prefecture of Honghe, Yunnan  province].

PMID- 27032123
TI  - Knee Arthroplasty Surgeons: coping with the pressure of treating  patients   with
      high expectations.

PMID- 27032122
TI  - [Relationship between obesity and hypertension/lipids in chef].

PMID- 27032124
TI  - State Policies on Service Dogs for Military Veterans.
AB  - U.S. service members returning home from combat often face physical, mental and
      emotional challenges. Providing service dogs to these veterans is one method
      being used successfully to help address the difficulties they face. Under the
      federal Americans with Disabilities Act (ADA), a service animal is defined as
      "any dog that is individually trained to do work or perform tasks for the benefit
      of an individual with a disability, including a physical, sensory, psychiatric,
      intellectual or other mental disability." The work the dog undertakes must be
      directly related to the person's disability. Examples include guiding people who
      are blind, pulling a wheelchair, alerting a person with hearing loss, protecting
      a person having a seizure, and calming someone with post-traumatic stress
      disorder (PTSD) during an anxiety attack or psychiatric episode.

PMID- 27032125
TI  - Addressing Depression.

PMID- 27032126
TI  - Covering and Reimbursing Telehealth Services.
AB  - Policymakers who are striving to achieve better health care, improved health
      outcomes and lower costs are considering new strategies and technologies.
      Telehealth is a tool that uses technology to provide health services remotely,
      and state leaders are looking to it now more than ever as a way to address
      workforce gaps and reach underserved patients. Among the challenges facing state
      lawmakers who are working to introduce or expand telehealth is how to handle
      covering patients and reimbursing providers.

PMID- 27032127
TI  - Benefits and Limits of Abuse-Deterrent Painkillers.
AB  - Abuse of opioid prescription products, meant to reduce pain, has been making
      headlines in recent years as a growing problem not only in rural and urban areas,
      but also across population groups. Policymakers looking for effective ways to
      reduce such abuse are employing various strategies, including setting up
      prescription drug monitoring programs. Another approach gaining attention
      involves encouraging or requiring the use of prescription drug formulas that can
      help deter abuse of opioid painkiller products.

PMID- 27032128
TI  - Using Peers to Improve Mental Health Treatment.

PMID- 27032129
TI  - Physician Orders for Life-Sustaining Treatment.

PMID- 27032130
TI  - Editorial.

PMID- 27032131
TI  - Superannuation reform aiming to rebalance bias against women.

PMID- 27032132
TI  - The Australian Parliament to examine long service leave.

PMID- 27032133
TI  - GENERATION NEXT. HELPING GRADUATE NURSES AND MIDWIVES FIND JOBS.

PMID- 27032134
TI  - AHPRA--Notifications, investigations, processes and outcomes.

PMID- 27032135
TI  - Questions of science.

PMID- 27032136
TI  - The role of sleep in patient recovery.

PMID- 27032137
TI  - Impact of financial difficulty on health and aged care choices.

PMID- 27032138
TI  - Mental illness: part of the non-communicable diseases epidemic.

PMID- 27032139
TI  - App challenged: Are midwives prepared?

PMID- 27032140
TI  - Minutes matter to save a life.

PMID- 27032141
TI  - Advancing initiatives in care of cognitively impaired patients in acute care
      settings.

PMID- 27032142
TI  - Using sound therapy to ease agitation amongst persons with dementia: a pilot
      study.

PMID- 27032143
TI  - The resilience of aged care nurses.

PMID- 27032144
TI  - Virtual human technology researches decisions about care for patients with
      dementia.

PMID- 27032145
TI  - CRANAplus Position Paper: Older Persons--remote context.

PMID- 27032146
TI  - What do people over 55 want from mobility aids?

PMID- 27032147
TI  - Family focus on bladder cancer research.

PMID- 27032148
TI  - Dementia: Responding to a national and international health priority.

PMID- 27032149
TI  - Community health, aged care and a stable home: an important relationship.

PMID- 27032150
TI  - Costs of complications in hospitalised dementia patients.

PMID- 27032151
TI  - Rates of complications in hospitalised dementia patients.

PMID- 27032152
TI  - Care collaboration.

PMID- 27032154
TI  - Achieving person-centredness with older people in residential aged care.

PMID- 27032153
TI  - Healthy ageing strategies.

PMID- 27032155
TI  - Consumer Directed Care: A client experience.

PMID- 27032156
TI  - The McKellar Guidelines: helping plan care for older people with diabetes.

PMID- 27032157
TI  - Accessing mental health services for older people in rural South Australia.

PMID- 27032158
TI  - Simulation: Preparation of Bachelor of Nursing students for aged care practice.

PMID- 27032159
TI  - Changing clinical education and stamping out the stigma.

PMID- 27032160
TI  - The facts about low dose methotrexate.

PMID- 27032161
TI  - The answer is not RNs.

PMID- 27032162
TI  - Money crunching in aged care makes it impossible.

PMID- 27032163
TI  - Marriage equality and discrimination.

PMID- 27032164
TI  - Increasing reporting in the media of alcohol fuelled violence in Australia.

PMID- 27032165
TI  - Social Media in Health Care: Safeguarding Healthcare Staff.

PMID- 27032166
TI  - Inpatient or observation: Will the difference ever be clear?
AB  - It's been more than two years since the Two-Midnight rule went into effect, but
      the Centers for Medicare & Medicaid Services' attempt to clear up confusion about
      patient status just has people more uncertain. Case managers should monitor
      patients at every access point in the hospital and work with the admitting
      physicians to ensure that patients are in the proper status. Observation patients
      should be easily identified, preferably in a dedicated observation unit, so
      clinicians know to give them priority and either admit or discharge them. Now
      that CMS has agreed that some short stays may qualify as inpatient admissions
      based on physician judgment, case managers should make sure the documentation
      supports the admission.

PMID- 27032167
TI  - Review patients at every entry point to ensure patient status.

PMID- 27032168
TI  - Who's in observation? The treatment team needs to know instantly.

PMID- 27032169
TI  - Ensure that patients meet criteria, documentation supports it.

PMID- 27032170
TI  - CASE MANAGEMENT INSIDER. Case management's role in the new proposed bundled
      payment program.
AB  - The CCJR program is a complex one. It is important that case managers, social
      workers, and case management leaders educate themselves on the program and what
      they can do to be successful partners in this process. Use total joints as a
      pilot to prepare for future bundles. They are on the way!

PMID- 27032171
TI  - Ensure that services observation patients receive are necessary and timely.
AB  - CMS changed the payment methodology for observation services to a flat rate that
      covers most major services patients receive during the observation period.
      Hospitals can no longer bill for individual services such as injections,
      infusions, MRIs, and other services, but will receive a flat fee for the entire
      stay, which in some cases may not cover the observation stay. Case managers
      should monitor observation patients closely and ensure that the services they
      receive are necessary for the physician to make a decision on whether to admit or
      discharge the patient. Collect data on avoidable delays in observation that are
      due to inappropriate tests and procedures and how the cost of the procedures
      affect the hospital's bottom line.

PMID- 27032172
TI  - Hospitals push back against reimbursement cuts due to Two-Midnight rule.
AB  - The American Hospital Association (AHA) and other hospitals are suing CMS,
      challenging the 0.2% cut in Medicare reimbursement that CMS instituted to
      compensate for the financial effect of the Two-Midnight rule. CMS' actuaries
      reported that inpatient claims are likely to increase under the rule, resulting
      in $220 million additional reimbursement for hospitals. Hospitals disagree and a
      study commissioned by the AHA concluded that the CMS study was based on data not
      available to the public and that data from the Medicare Provider and Analysis
      Review (MedPAR) would lead to a different conclusion. The AHA suit asks CMS to
      rescind the cut, restore the base rate for Medicare payments to its previous
      level, and reimburse hospitals retroactively for the reductions.

PMID- 27032173
TI  - Utilization review process calls for assessing patients at every point of entry.
AB  - Dartmouth-Hitchcock Medical Center in Lebanon, NH, reviews patients at every
      point of access to get their status right up front. Case managers cover the
      emergency department, utilization review nurse review surgical patients, and
      physician advisors are on call to the transfer center. Observation patients are
      placed in a clinical decision unit next to the emergency department; surgical
      patients who need a longer-than-normal recovery period are monitored in a short
      stay unit. The electronic medical record allows clinicians to see what the other
      disciplines are doing in real time.

PMID- 27032174
TI  - [The JAID/JSC Guidelines to Clinical Management of Infections Diseases (Urinary
      tract infections and Male genital infections)].

PMID- 27032175
TI  - [The JAID/JSC Guidelines to Clinical Management of Infectious Diseases
      (Intestinal infection)].

PMID- 27032176
TI  - [Two Outbreaks of Yersinia enterocolitica O:8 Infections in Tokyo and the
      Characterization of Isolates].
AB  - Although the number of outbreaks caused by Yersinia enterocolitica has been very
      small in Japan, 4 outbreaks were occurred during the 2 years between 2012 and
      2013. We describe herein 2 outbreaks which were examined in Tokyo in the present
      study. Outbreak 1: A total of 39 people (37 high school students and 2 staff)
      stayed at a hotel in mountain area in Japan had experienced abdominal pain,
      diarrhea and fever in August, 2012. The Y. enterocolitica serogroup O:8 was
      isolated from 18 (64.3%) out of 28 fecal specimens of 28 patients. The infection
      roots could not be revealed because Y. enterocolitica was not detected from any
      meals at the hotel or its environment. Outbreak 2: A total of 52 students at a
      dormitory had diarrhea and fever in April, 2013. The results of the
      bacteriological and virological examinations of fecal specimens of patients
      showed that the Y. enterocolitica serogroup O:8 was isolated from 24 fecal
      specimens of 21 patients and 3 kitchen staff. We performed bacteriological and
      virological examination of the stored and preserved foods at the kitchen of the
      dormitory to reveal the suspect food. For the detection of Y. enterocolitica,
      food samples. together with phosphate buffered saline (PBS) were incubated at 4
      degrees C for 21 days. Then, a screening test for Y. enterocolitica using
      realtime-PCR targeting the ail gene was performed against the PBS culture. One
      sample (fresh vegetable salad) tested was positive on realtime-PCR. No Y.
      enterocolitica was isolated on CIN agar from the PBS culture because many
      bacteria colonies other than Y. enterocolitica appeared on the CIN agar. After
      the alkaline-treatments of the culture broth or the immunomagnetic beads
      concentration method using anti-Y. enterocolitica O:8 antibodies, Y.
      enterocolitica O:8 which was the same serogroup as the patients' isolates was
      successfully isolated from the PBS culture. The fresh vegetable salad was
      confirmed as the incrimination food of this outbreak.

PMID- 27032178
TI  - [Successful Treatment of Seasonal Influenza A (H3N2) infection-related
      Hemophagocytic Lymphocytosis in an Elderly Man].
AB  - A 79-year-old man experienced severe chronic obstructive pulmonary disease (COPD)
      and was receiving treatment for ischemic heart disease. Starting from dizziness
      and chilliness, he lost consciousness after few days. He was taken to our
      emergency department. On initial evaluation, he complained of dyspnea and was
      afebrile with a pulse rate, blood pressure, and respiratory rate of 105
      beats/min, 112/98mmHg, and 28 breath/min, respectively. His respiratory sounds
      were clear and chest radiography did not show any abnormal shadows, but his
      arterial blood gas examination showed type II respiratory failure. Because the
      nasopharyngeal seasonal influenza A virus (IAV) test was positive, the patient
      was admitted with the diagnosis of acute exacerbation of COPD due to IAV. We
      administered peramivir, a specific anti-influenza drug, and started mechanical
      ventilation. Over time, he started to show signs of disseminated intravascular
      coagulation, such as multiple organ failure and thrombocytopenia. Subsequently,
      blood tests showed elevation of ferritin and soluble interleukin 2 receptor
      (sIL2R); microscopic examination of the peripheral blood revealed
      hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis (HLH) due to IAV
      was diagnosed and together with corticosteroid therapy, intravenous gamma
      globulin was administered from the 3rd clinical day. The patint was saved with
      our early diagnosis and treatment of HLH and was discharged on the 92nd clinical
      day. Viral-induced HLH, formerly known as virus-associated hemophagocytic
      syndrome (VAHS), leads to multiple organ failure due to a cytokine storm
      scattered by viral-infected pathogenic inflammatory cells. It is well known that
      pandemic swine flu causes secondary HLH leading to poor outcomes. Currently, not
      much is known about HLH due to seasonal flu; particularly, IAV (H3N2)-related HLH
      cases are rare and reported cases showed poor outcomes as well. With an early
      diagnosis and minimum immunotherapy, we report herein on a case of IAV (H3N2)
      related HLH which was treated successfully.

PMID- 27032177
TI  - [A Case of Peristomal Cutaneous Ulcer Following Amebic Colitis Caused by
      Entamoeba histolytica].
AB  - A 66-year-old Japanese male with a history of a rectal ulcer and rectovesical
      fistula following brachytherapy and radiotherapy for prostate cancer, who had
      undergone colostomy and vesicotomy presented with a painful peristomal ulcer of
      approximately 5 x 2.5cm adjacent to the direction of 6 o'clock of the stoma in
      his left lower abdomen. Although he was admitted to be treated with intravenous
      antibiotics and topical debridement, the ulcer was rapidly increasing. In the
      laboratory findings, WBC was 12,400/MUL, CRP was 16.9 mg/dL, ESR was 105mm in the
      first hour. Contrast enhanced CT images showed a wide high density area of skin
      and subcutaneous tissue around the stoma and dillitation of the transverse and
      descending colon. Colonoscopy showed furred profound ulcers in the rectum. A
      biopsy from the ulcer floor submitted to histopathology showed necrotic tissue
      with a mixed inflammatory infiltrates mainly composed of neutrophils and
      lymphocytes in the dermis. We suspected pyoderma gangrenosum with an inflammatory
      bowel disease in the beginning. Although he was started on oral prednisolone 60
      mg daily, the ulcer did not respond to treatment. Additional methylprednisolone
      pulse therapy, intravenous cyclosporine and granulocytapheresis were also
      ineffective. A biopsy specimen from the skin ulcer margin showed
      erythrophagocytosis by trophozoites of amebae which were identified on PAS
      stained slides. The PCR method and stool examination showed positive for
      Entamoeba histolytica (E. histolytica), but serum antibodies were negative.
      Within two weeks of treatment with oral metronidazole 2,250 mg/day and topical
      metronidazole ointment, resolution of the ulcer was observed, then the
      prednisolone dosage was tapered. A split-thickness skin graft was used to cover
      the ulcer with a successful result. Even though we originally misdiagnosed this
      case, we finally reached a diagnosis of amebiasis. It is important to take
      account of amebiasis in the differential diagnosis of intractable ulcers which
      can be contaminated by feces.

PMID- 27032179
TI  - Pulmonary Histoplasmosis in a Japanese Man Infected During Travel to Mexico and
      Management of His Wife's Condition: A Case Report.
AB  - We report herein on the case of a 33-year-old Japanese man in whom an abnormal
      shadow was detected on chest radiography during a medical checkup after a 1-year
      stay in Mexico. Chest computed tomography showed a nodule in the left lower lobe
      adjacent to the visceral pleura. Histopathologic examination of a thoracoscopic
      partial pulmonary resection specimen showed coagulation necrosis with a number of
      yeast-like forms on Grocott staining. In addition, serum anti-Histoplasma
      antibody positivity was detected with an enzyme-linked immunosorbent assay, and
      Histoplasma-specific nested real-time polymerase chain reaction results were
      positive in the pulmonary region. Finally, pulmonary histoplasmosis was
      diagnosed, and treatment with itraconazole was initiated. The patient's wife who
      had accompanied him to Mexico was asymptomatic and was not found to have
      histoplasmosis based on diagnostic imaging and serological findings. Although
      rare in Japan, histoplasmosis should be considered in the differential diagnosis
      of pulmonary lesions in patients who have returned from travel to endemic areas.

PMID- 27032180
TI  - [Dengue Fever Infection Confirmed with an Epidemiological Survey and Genetic
      Analysis: The Case was Suspected as SFTS Based on the Primary First Information].

PMID- 27032181
TI  - [Comparison of Performance between Stool and Rectal Swab Specimens for the
      Norovirus Rapid-diagnostic Kit].

PMID- 27032182
TI  - Inspiring Nurses to See the Extraordinary in their Ordinary.

PMID- 27032183
TI  - Looking in at Our World: Sharing the Patient-Caregiver Experience.

PMID- 27032184
TI  - Connecting Nebraska--The Nebraska Health Information Initiative.

PMID- 27032185
TI  - Two New Eremophilane Sesquiterpenes and One New Resorcinol from Ligularia
      knorringiana.
AB  - Two new eremophilane sesquiterpenes, 12-oxa-1beta, 5beta,8,9abeta-tetramethyl
      4alpha,5-ethano-4abeta-hydroxy-7beta,10abeta-epoxy-9beta-angeloyloxy
      1,2,3,4,4a,5,6,7,9,9a,10,10a- dodecahydro-anthracen-13-on (knorringianalarin A,
      1) and 6,9-dien-8-oxoeremophil-12-nor-11-ketone (knorringianalarin B, 2), and a
      new resorcinol, 4-acetyl- 6-(2-methylpropionyl)-1,3-resorcinol (knorringianalarin
      C, 3) were isolated from the roots and rhizomes of Ligularia knorringiana,
      together with three known eremophilane sesquiterpenes (4-6). The structures of
      the new compounds were identified by spectroscopic methods including 2D-NMR
      techniques.

PMID- 27032186
TI  - Chemical Lineages of Ligularia fischeri.
AB  - Six Ligularia fischeri samples, two from Sichuan (samples 1 and 2) and four from
      Chongqing (samples 3-6), were examined for root chemicals and the DNA sequence of
      the internal transcribed spacers of the ribosomal RNA gene. Samples 2 and 3
      contained benzofurans. The isolation of benzofurans shows that the chemical
      diversity in L. fischeri is higher than previously reported. Samples 1, 4, 5, and
      6 contained eremophilanes. However, the compounds were different between sample 1
      and samples 4-6, indicating variation within eremophilane producers. DNA data
      indicated that introgression could be a mechanism of benzofuran production in
      sample 2 and that sample 1 and samples 4-6 were genetically separate.

PMID- 27032187
TI  - Diversity in Chemical Constituents of Ligularia longihastata Collected in China.
AB  - Root constituents of Ligularia longihastata were examined for the first time.
      Fourteen eremophilane sesquiterpenes, including two new eremophilanes identified
      as 3alpha-isobutyroyloxy-7betaH-eremophila-9,11-dien-8-one and 3beta-angeloyloxy
      1beta,10beta-epoxyfuranoeremophilan-9-one, and three eudesmanes were isolated.
      From samples collected in Baiyu County, Sichuan Province, furanoeremophilane
      derivatives were isolated, while various eremophilan-8-ones were isolated from
      samples collected in Kangding County, Sichuan. The results suggest chemical
      diversity in the species.

PMID- 27032188
TI  - Chemical Constituents of Ligularia wilsoniana Collected in Chongqing, China.
AB  - The chemical constituents of Ligularia wilsoniana were studied for the first
      time, using four samples collected in Chongqing City, China. Two new compounds,
      6beta-(2',3'-epoxy-2'-methylpropanoyloxy)-beta,10beta-epoxyfuranoeremophilane and
      11alphaH-6beta-(2'-hydroxymethylacryloyloxy)-1beta,10beta;7beta,8beta-
      diepoxyeremophilanolide, as well as eight known compounds, were isolated from one
      of the samples, while three to four known furanoeremophilanes were isolated from
      the other three samples. No compound was common to the two classes of the
      samples, demonstrating the presence of at least two chemotypes of this species.

PMID- 27032189
TI  - Terpenoids, Flavonoids and Acetogenins from Some Malagasy Plants.
AB  - Humulanes, drimanes, ent-kaurane, lupane, cycloartane, flavanone, flavones and
      quinol derivatives were isolated from Malagasy Cussonia vantsilana, Helichrysum
      gymnocephalum, Phyllarthron madagascariense, Gomphocarpus fructicosus, Cinnamosma
      sp. and C. fragrans, and their structures elucidated by using extensive NMR
      analysis. A mixture of a few flavones and/or lupane triterpene showed
      antimicrobial activity against Mycobacterium smegmatis and Pseudomonas
      aeruginosa.

PMID- 27032191
TI  - Further Insight into Polycyclization Cascades of Acyclic Geranylfarnesol and its
      Acetate by Squalene-hopene Cyclase from Alicyclobacillus acidocaldarius.
AB  - The enzymatic reactions of geranylfarnesol (8) and its acetate 9, classified as
      sesterterpenes (C25), using squalene-hopene cyclase (SHC) were investigated. The
      enzymatic reaction of 8 afforded 6/6-fused bicyclic 20, 6/6/6-fused tricyclic 21,
      and 6/6/6/6-fused tetracyclic compounds 22 and 23 as the main products (35%
      yield), whereas that of 9 afforded two 6/6/6-fused tricyclic compounds 24 and 25
      in a high yield (76.3%) and a small amount (5.0%) of 26 (the acetate of 22). A
      significantly higher conversion of 9 indicates that the arrangement of the
      substrate in the reaction cavity changed. The lipophilic nature and/or the
      bulkiness of the acetyl group may have changed its binding with SHC, thus placing
      the terminal double bond of 9 in the vicinity of the DXDD motif of SHC, which is
      responsible for the proton attack on the double bond to initiate the
      polycyclization reaction. The results obtained for 8 are different to some extent
      than those reported by Shinozaki et al. The products obtained in this study were
      deprotonated compounds; however, the products reported by Shinozaki et al. were
      hydroxylated compounds.

PMID- 27032190
TI  - Two New Diterpenoids from Salvia przewarskii.
AB  - One abietane-type and one dinoricetexane-type diterpenoid, salviskin A (1) and
      salviskin B (2), respectively, together with fourteen known diterpenoids, were
      isolated from Salvia przewarskii. Structural elucidation of these compounds was
      performed by spectroscopic methods including 2D NMR. The compounds isolated were
      evaluated for their cytotoxicity against HeLa and HL-60 cells.

PMID- 27032192
TI  - Six New Lanostane Triterpenoids from the Fruiting Body of Tyromyces sambuceus and
      Antiproliferative Activity.
AB  - During the search for secondary metabolites with antiproliferative activity, six
      new lanostane triterpenoids, tyrosamic acids A-F (1-6) together with ten known
      compounds (7-16), were isolated from the fruiting body of Tyromyces sambuceus.
      Their structures were elucidated using MS analyses, extensive 2D-heteronuclear
      NMR data interpretation and the structure of 3 was further confirmed by single
      crystal X-ray data analyses. All lanostane triterpenoids (1-16) possesses a
      carboxy group at C-20 position and their strength of antiproliferative activity
      was affected by the presence or absence of a hydroxy group at C-15 position and
      at the side chain. Four of the compounds (1, 6, 10, 14) showed antiproliferative
      activities against human cancer cell lines with IC50 values of 16.8-48.3 uM (HL
      60).

PMID- 27032193
TI  - Constituents of the Leaves of Pandanus utilis.
AB  - Nineteen compounds, including seven triterpenoids (1-7), five steroids (8-12),
      four cyclohexenone derivatives (13-16), two benzenoid glycosides (17 and 18) and
      one lignan (19), were isolated and separated from the leaves of Pandanus utilis
      through bioactivity-guided fractionation. Among them, one new lanosterol- type
      triterpenoid was found and named as (24R)-24-methyl-5a-4-demethyllanosta-9(11),25
      dien-3beta-ol (1). The structures of the isolates were determined by mass and
      spectroscopic analyses, and the compounds were subjected to anti-inflammatory,
      anti-oxidative and cytotoxic assays.

PMID- 27032194
TI  - Chemical Constituents of the Aerial Parts of Euphorbia nematocypha.
AB  - Chemical constituents of the dried aerial parts of Euphorbia nematocypha were
      investigated. A new oleanane triterpenoid, trans, trans-2',4'- hexadienedioicacid
      1'-beta-amyrin ester (1), together with, beta-amyrin (2), beta-amyrin acetate
      (3), betulinic acid (4), ellagic acid (5), oleanolic acid (6), beta-sitosterol
      (7), kaempferol (8), quercetin (9), lupeol (10) and pseudo-taraxasterol (11) were
      isolated from the methylene chloride extract. Their structures were elucidated on
      the basis of extensive spectroscopic (1D- & 2D-NMR) and ESI-MS analysis and
      comparison with data reported in the literature. The new isolated triterpenoid
      showed moderate cytotoxic activities against HeLa and MCF-7cell lines.

PMID- 27032195
TI  - Triterpene Galloyl Esters from Edible Acorn of Castanopsis cuspidata.
AB  - Polyphenols of edible acorns of Castanopsis cuspidata were examined and two
      triterpene galloyl esters were isolated. Based on two-dimensional NMR
      spectroscopic evidence the structures were determined to be 3,24-di-O-galloyl
      2alpha,3beta-23,24-tetrahydroxyolean-12-en-28-oic acid (1) and 3,24-di-O-galloyl-
      2alpha,3beta-23,24-tetrahydroxyurs-12-en-28-oic acid (2). The triterpene
      hexahydroxydiphenoyl esters, which had been found in the leaves, were not
      detected in the acorns.

PMID- 27032196
TI  - Structure Revision of (22E)-Ergosta-7,22-diene-3beta,5alpha,6beta,9alpha,14alpha-
      pentol from the Spores of the Medicinal Mushroom Ganoderma lucidum.
AB  - Careful reexamination of the published 1H and 13C NMR spectral data of (22E)
      ergosta-7,22-diene-3beta,5alpha,6beta,9alpha,14alpha-pentol (1), isolated from
      the spores of the medicinal mushroom Ganoderma lucidum, indicates that, in
      reality, the compound is (22E)-ergosta-7,22-diene
      3beta,5alpha,6beta,9alpha,14beta-pentol (5).

PMID- 27032197
TI  - Bioassay-Guided Isolation of Compounds from Datura stramonium with TRAIL
      Resistance Overcoming Activity.
AB  - TRAIL is a potent inducer of apoptosis in most cancer cells, but not in normal
      cells, and therefore has deserved intense interest as a promising agent for
      cancer therapy. In the search for bioactive natural products for overcoming TRAIL
      resistance, we previously reported a number of active compounds. In our screening
      program on natural resources targeting overcoming TRAIL-resistance, activity
      guided fractionation of the MeOH extract of Datura stramonium leaves led to the
      isolation of three alkaloids--scopolamine (1), trigonelline (2), and tyramine
      (3). Compounds 1, 2, and 3 exhibited TRAIL-resistance overcoming activity at 50,
      150, and 100 uM, respectively in TRAIL-resistant AGS cells.

PMID- 27032198
TI  - Three New Oxidation Products Produced from Epigallocatechin-3- O-gallate and
      Epicatechin-3-O-gallate.
AB  - During chemical studies on uncharacterized black tea polyphenols, the enzymatic
      oxidation of a mixture of epigallocatechin-3-O-gallate (1) and epicatechin-3-O
      gallate (2) was examined, and three new dimeric products together with six known
      catechin dimers were isolated. Two of the new compounds have
      tricyclo[5.2.2.02,6]undecane and tricyclo[5.2.1.02,6]decane carboxyl structures
      generated by oxidative coupling between two pyrogallol-B-rings of 1. Another new
      product was a dimer connected by a C-C bond between the B-ring of 1 and a galloyl
      group of 2.

PMID- 27032199
TI  - Stereochemistry of a Rhododaurichromanic Acid Derivative.
AB  - A rhododaurichromanic acid A derivative was synthesized from the naturally
      occurring daurichromenic acid in enantiomeric pure form. Its absolute
      configuration was elucidated by applying VCD, ECD and DFT calculations.

PMID- 27032200
TI  - Hydroxylation and Glycosylation of Phenylpropanoids by Cultured Cells of
      Phytolacca americana.
AB  - Hydroxylation and glycosylation of cinnamic acid, p-coumaric acid, caffeic acid,
      and ferulic acid were investigated using cultured plant cells of Phytolacca
      americana as biocatalysts. Regioselective hydroxylation at the 4-position of
      cinnamic acid and 3-position of p-coumaric acid was observed. Although cinnamic
      acid was transformed to mono-glucoside products, di-glycosylation occurred in the
      case of the biotransformation of p-coumaric acid, caffeic acid, and ferulic acid.

PMID- 27032201
TI  - Glycosylation of trans-Resveratrol by Cultured Plant Cells under Illumination of
      LEDs.
AB  - Incubation of cultured cells of Strophanthus gratus with trans-resveratrol gave
      its 4'-O-beta-D-glucoside as the major product in addition to its 3-O-beta-D
      glucoside under white and red light-emitting diodes (LEDs). Use of blue LEDs as
      light sources for biotransformation of trans-resveratrol much improved the yield
      of its beta-D-glycosides and changed the composition of products, that is, 3-O
      beta-D-glucoside was the major product and 4'-O-beta-D-glucoside was the minor
      one.

PMID- 27032202
TI  - Discovery of a Novel Diterpene in Brown Propolis from the State of Parana,
      Brazil.
AB  - Propolis is a resinous substance collected by honeybees from certain plant
      sources. The components of propolis depend on the vegetation of the area in which
      apiculture is practiced. In Brazil, there are several types of propolis including
      'green,' 'red' and 'brown'. Brazilian brown propolis from the state of Parana
      characteristically includes diterpenes, and we discovered a novel clerodane
      diterpene, rel-(5S,6S,8R,9R,10S,18R,19S)-18,19-epoxy-2-oxocleroda-3,12(E),14-
      triene-6,18,19-triol 18,19-diacetate 6-benzoate (3) and five known diterpenes (1,
      2, 4, 5 and 6). The chemical structure of the novel diterpene 3 was determined
      using 1D- and 2D-NMR spectroscopic analyses. Furthermore, the activities of the
      isolated diterpenes on growth inhibition of several human cancer cell lines
      (LNCaP, MCF-7, DLD-1 and A549) were evaluated in vitro; diterpene 3 exhibited a
      potent inhibition of cell growth, and its activity was approximately 15 times
      higher than that of the other diterpenes.

PMID- 27032203
TI  - New 6,6-Spiroketal from the Alga-Derived Fungus Penicillium lividum.
AB  - The new 6,6-spiroketal,sargassopenilline H (1), and known peneciraistin C (2)
      have been isolated from an EtOAc extract of the marine-derived fungus Penicillium
      lividumKMM 4663. The structure of the new metabolite was determined by HR ESIMS
      and 1D and 2D NMR spectroscopy. Sargassopenilline H (1) in non-cytotoxic
      concentration inhibited colony formation of RPMI-7951 and MDA-MB-231 cell lines.

PMID- 27032204
TI  - Comparative Study of Alkaloid Pattern of Four Bulgarian Fumaria species.
AB  - The alkaloid pattern of four Fumaria species (Fumaria kralikii, Fumaria
      rostellata, Fumaria schleicherii, Fumaria thureii) growing in Bulgaria was
      investigated by GC-MS and twenty isoquinoline alkaloids were determined.
      Phytochemical investigation of the alkaloid composition on Fumaria thuretii Boiss
      was made for the first time. The alkaloid profile of the species was compared at
      two levels, between different species and within two species from different
      habitats. Two chemotypical groups, based on the types of isoquinoline alkaloids
      were suggested. To group A belong species F. kralikii, F. rostellata (F. r. 1)
      and F. thuretii containing more than 50% spirobenzylisoquinoline alkaloids of the
      crude alkaloid mixtures. To group B belong species F. rostellata (F. r. 2) and F.
      schleicherii containing more than 40% protopine alkaloids and relatively high
      percentage phthaldeisoquinoline alkaloids (11-19%). In group A
      phthaldeisoquinoline alkaloids were not detected.

PMID- 27032205
TI  - Synthesis of beta-Hydroxytyrosine, A Component of Burkholdines.
AB  - The preparation of four stereoisomers of beta-hydroxytyrosine containing
      burkholdines is described. Enantio-pure syn beta-hydroxytyrosine was synthesized
      using Sharpless aminohydroxylation. To obtain anti beta-hydroxytyrosine, the
      cinnamate derivative was oxidized to give the optical active diol derivative by
      the AD-mix and subsequently, the a-hydroxy group was converted to amine.
      Deprotection of the acid-sensitive beta-hydroxytyrosine derivatives was
      successively accomplished by brief immersion in 4N HCl/dioxane. All prepared
      stereoisomers of beta-hydroxytyrosine were available for solid and solution phase
      peptide synthesis and amino acid analysis.

PMID- 27032206
TI  - Acidiscalide, A New Glycosylated Macrolide from the Marine Actinomycete
      Streptomyces acidiscabies.
AB  - A new macrolide named acidiscalide (2), and a known protein synthesis inhibitor,
      cycloheximide (1), were isolated from the culture broth of a strain of
      actinomycete, Streptomyces acidiscabies, coded SCTA0002 collected from the coast
      of Okinawa. The structure of acidiscalide (2) was elucidated to be a glycosylated
      macrolide having a 24-membered ring on the basis of spectroscopic analysis.
      Although the stereochemistry could not be determined due to decomposition in the
      course of the study, it was confirmed that acidiscalide (2) possessed a new
      molecular scaffold.

PMID- 27032207
TI  - Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition
      and Cellular Localization.
AB  - SMTPs, a family of natural small molecules that effectively treat ischemic
      stroke, are subject to clinical development. SMTPs enhance plasminogen activation
      and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous
      thrombolysis and anti-inflammation. The SMTP molecule consists of atricyclic
      gamma-lactam moiety, an isoprene side-chain, and an N-linked side-chain. Here, we
      investigate the yet-to-be-characterized function of the isoprene side- chain of
      SMTPs in sEH inhibition and cellular distribution. The results demonstrated that
      oxidative modification as well as truncation of the side-chain abolished epoxide
      hydrolase inhibition. The introduction of a terminal hydroxy group exceptionally
      unaffected epoxide hydrolase, but led to impaired cellular localization,
      resulting in diminution of cellular epoxide hydrolase inhibition. Thus, the
      isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase
      inhibition and cellular localization.

PMID- 27032208
TI  - A New Neolignan from Coix lachryma-jobi var. mayuen.
AB  - A new neolignan, named coixide A (1), along with fifteen known compounds, (7R,8S)
      3'-demethyl-dehydrodiconiferyl alcohol-3'-O-beta-glucopyranoside (2), (7R,8)-3'
      demethyl-9'-butoxy-dehydrodiconiferyl-3'-O-beta-glucopyranoside (3),adenosine
      (4), 2-O-caffeoyl isocitricacid (5), pseudolaroside A (6), 2-hydroxy-7-methoxy
      (2H)-1,4-benzoxazin-3(4H)-one (7), 2-O-beta-glucopyranosyl-7-methoxy-2H-1,4
      benzoxazin-3(4H)-one (8), 2-O-beta-glucopyranosyl-4-hydroxy-7- methoxy-2H-1,4
      benzoxazin-3(4H)-one (9), 2-O-beta-D-glucopyranosyl-7-hydroxy-2H-1,4-benzoxazin
      3(4H)-one (10), p-coumaric acid ethyl ester (11), caffeic acid ethyl ester (12),
      p-coumaric acid (13), cis-N-p-coumaroyltyramine (14) trans-N-p-coumaroyltyramine
      (15), and coixol (16) have been isolated from Coix lachryma-jobi var. mayuen.
      Their chemical structures were elucidated by chemical evidence on the basis of
      spectroscopic and MS data, and as well as by comparison with those reported.

PMID- 27032209
TI  - Synthesis and Larvicidal Activity of Phrymarolin Derivatives against Culex
      pipiens pallens.
AB  - Twenty-eight new phrymarolin derivatives, including twenty-one ethers, six esters
      and a dehydroxy phrymarolin, were prepared from phrymarolin I and the structures
      of all the derivatives were confirmed by 1H NMR and 13C NMR spectroscopic and MS
      data analyses. Larvicidal activities of these phrymarolin analogues were assayed
      against 4th instar larvae of Culex pipiens pallens. The ester derivatives of
      phrymarolin showed lower larvicidal activity than phrymarolin I, but some of the
      ether derivatives and dehydroxy phrymarolin showed much higher activity. Two
      ether derivatives, 1-18 and 1-19, showed significant larvicidal activity with
      LC50 values of 1.89 and 7.78 mg/L, respectively.

PMID- 27032210
TI  - Antimicrobial Constituents from Allium hookeri Root.
AB  - In this study, we partially purified the ethyl acetate soluble fraction of the
      ethanol extract of the root of Allum hookeri. We identified seven compounds,
      benzoic acid, tetradecanoic acid, hexadecanoic acid, ferulic acid, cinnamic acid,
      octadecanoic acid and hexanedioic acid, that have antimicrobial activity using GC
      MS, and evaluated the antimicrobial susceptibility and MIC (minimum inhibitory
      concentration) against multidrug-resistant bacteria.

PMID- 27032211
TI  - Profiling of Gallic and Ellagic Acid Derivatives in Different Plant Parts of
      Terminalia arjuna by HPLC-ESI-QTOF-MS/MS.
AB  - Terminalia arjuna is a medicinal plant used in ethnomedicine and the codified
      traditional medicine. A number of active constituents are reported, but there is
      no information on the whole range of gallic and ellagic acid derivatives present
      in this plant A rapid and sensitive analytical method was developed using reverse
      phase high-performance liquid chromatography coupled with quadrupole time-of
      flight mass spectrometry (HPLC-ESI-QTOF-MS/MS) for qualitative analysis to
      determine the array of bioactive phytochemicals and their variations in different
      plant parts viz. bark, unripe fruit, ripe fruit, leaf, root and stem. Separation
      was performed on a Thermo Betasil C8 column (250 mm x 4.5 mm, 5 um) with a mobile
      phase consisted of 0.1% formic acid aqueous solution and acetonitrile at a flow
      rate of 0.5 mL/min in 55 min. A wide range of constituents of T. arjuna were
      characterized and broadly grouped as 27 gallic acid and 52 ellagic acid
      derivatives.

PMID- 27032212
TI  - Bioactive Constituents and Antioxidant Activity of Some Carpathian Basin honeys.
AB  - Unifloral honeys have a high commercial value and should undergo a strict quality
      control before marketing. This study aimed at determining floral origin,
      polyphenolic compounds and antioxidant activity in 7 samples marketed as lavender
      and thyme honeys. The samples were subjected to pollen analysis to confirm their
      botanical origin. Coupled chromatographic techniques (HPLC-DAD-ESI-MS) were
      optimized for the separation and identification of polyphenolic compounds. The
      antioxidant properties of the samples were determined by spectrophotometric
      methods. Pollen profile analysis revealed that only 3 out of 5 alleged lavender
      honeys contained a low percentage (0.6-1.5) of lavender pollen; and there were
      only traces (0.1-0.6%) of thyme pollen in the alleged thyme honeys. Polyphenolic
      constituents did not allow for the clear separation of honey samples, revealing
      no marker compounds previously associated with lavender and thyme honeys. All
      samples contained large amounts of chlorogenic acid, chrysin, hesperetin,
      kaempferol and p-coumaric acid; as well as abscisic acid, a plant hormone known
      to be present in floral nectar and honey. Our results suggest that only one of
      five alleged lavender honeys and neither of the two alleged thyme honeys are true
      unifloral honeys. However, they can still provide various health benefits, such
      as being good sources of antioxidants. There was no relationship between the
      antioxidant activity and the uni- or multifloral character of the honey samples.
      Total phenolic content and antioxidant activity was the lowest in the honey
      sample with lavender and the highest in one of the alleged lavender honeys. Our
      findings highlight the importance of microscopical and phytochemical analyses of
      honeys before marketing, to ensure satisfactory quality for customers.

PMID- 27032213
TI  - Comparative Histological and Phytochemical Study of Fallopia species.
AB  - Fallopia species which belong to the Polygonaceae family have several data
      related to their use in the Asian herbal medicine. In this work, some
      histological and phytochemical parameters of Fallopia japonica, F. sachalinensis,
      and F. x bohemica were analysed and compared. Rhizome and leaf samples were
      collected before, during, and after the flowering period at 3 habitats in
      Szombathely and 4 habitats in Baranya County, Hungary. The main histological
      characteristics of the stem, leaf and petiole were studied by light microscopy in
      cross section. Total tannin and anthraquinone contents were determined according
      to the official methods of the Hungarian Pharmacopoeia VIIIth (equal to the
      European Pharmacopoeia 6th). No species-specific markers were found in any plant
      part. In the rhizome, the highest tannin content was measured in Japanese
      knotweed, followed by Bohemian and giant knotweed in each period. The tannin
      content measured in each plant was higher in the leaves than in the rhizomes
      except F. japonica. The rhizome of F. japonica had the highest anthraquinone
      content before the flowering period, followed by F. x bohemica and F.
      sachalinensis. According to earlier and our preliminary data, Fallopia taxa are
      of great therapeutic promise in the future.

PMID- 27032214
TI  - Coconut Laurels: The Leaf Essential Oils from Four Endemic Australian Cryptocarya
      Species: C. bellendenkerana, C. cocosoides, C. cunninghamii and C. lividula
      (Lauraceae).
AB  - The leaf oils of four species of Cryptocarya, endemic to Australia, were
      examined. These species are known colloquially as 'coconut laurels' due to the
      purported distinctive aroma from the crushed foliage. C. cocosoides produced an
      oil in which bicyclogermacrene (3-26%), spathulenol (16-47%), massoia lactone (6
      pentyl-5,6-dihydro-2H-pyran-2-one) (11-15%), (6-heptyl-5,6-dihydro-2H-pyran-2-one
      (0.3-3%) and benzyl benzoate (0.2-5%) were the principal components. C.
      cunninghamii showed a second chemotype to that previously published, with benzyl
      benzoate (80.2%) being the principal component. C. bellendenkerana gave a leaf
      oil in which the major components were the terpenes limonene (8.3%), beta
      phellandrene (11.8%) and viridiflorene (9.1%). The principal components of the
      leaf oil of C. lividula were bicyclogermacrene (26.1%), spathulenol (21.1%) and
      beta-eudesmol (6.1%). Benzaldehyde and acetophenone were both present in amounts
      of less than 0.7%. Only C. cocosoides and C. cunninghamii have been found to have
      a 'coconut' aroma mainly due to the presence of massoia lactone and homologues.

PMID- 27032215
TI  - Chemical Composition of the Fruit Oils of Five Fortunella Species Grown in the
      Same Pedoclimatic Conditions in Corsica (France).
AB  - Fruit oil from five species of kumquat (Fortunella japonica, F. margarita, F.
      crassifolia, F. obovata, and F. hindsii) grown in the same pedoclimatic
      conditions have been analyzed by a combination of chromatographic and
      spectroscopic techniques. The compositions of the five fruit oils were strongly
      dominated by limonene (84.2-96.3%). Other components present with appreciable
      contents were myrcene (1.3-12.9%) and germacrene D (0.3-2.4%).

PMID- 27032216
TI  - Volatile Components Emitted from the Liverwort Marchantia paleacea subsp.
      diptera.
AB  - The volatile components from the thalloid liverwort, Marchantia paleacea subsp.
      diptera were investigated by HS-SPME-GC-MS analysis. The monocyclic monoterpene
      aldehyde, perillaldehyde was identified for the first time as the major component
      and its content was about 50% of the volatiles, along with beta-pinene, limonene,
      beta-caryophyllene, alpha-selinene and beta-selinene as minor volatiles. Using MD
      (Multi-dimensional) GC-MS analysis equipped with a chiral column as the second
      column, the chirality was determined of both perillaldehyde and limonene, which
      was considered as the precursor of perillaldehyde. Both compounds were (S)-(-)
      enantiomers (over 99.0 %) and (R)-enantiomers (less than 0.5 %). This is the
      first report of the existence of perillaldehyde in liverworts.

PMID- 27032217
TI  - Comparative Study of the Volatile Components of Fresh and Fermented Flowers of
      Alnus sieboldiana (Betulaceae).
AB  - Analysis of the volatile components present in the fresh male and female flowers
      and young leaves shows that 2-phenylethanol is the major component in all these
      three organs, which play a significant role in the strong resinous aromatic odor.
      The male flowers contained styrene as a second major compound. The level of
      styrene does not affect the male flowers odor concentration. The level of beta
      phenylethyl cinnamate and trans-methyl cinnamate in the fermented male flowers
      decreased as the fermentation time increased. This was due to the Penicillium
      enzymatic action on the fermented male flowers.

PMID- 27032218
TI  - Antimicrobial Constituents and Effects of Blended Eucalyptus, Rosemary,
      Patchouli, Pine, and Cajuput Essential Oils.
AB  - The synergistic antimicrobial activities of blended essential oil preparations
      composed of eucalyptus, rosemary, patchouli, pine and cajuput oils were evaluated
      against various pathogenic microorganisms. They exhibited antimicrobial activity
      in the agar disc diffusion assay against the Gram-positive bacteria,
      Staphylococcus aureus and S. epidenidis, the Gram-negative bacteria, Escherichia
      coli and Pseudomonas aeruginosa, and the yeast, Candida albicans. The minimum
      inhibitory concentration (MIC) of these preparations was evaluated by the broth
      microdilution method. We found that the best synergistic antibacterial
      preparation (the sum of fractional inhibitory concentrations, Sigmafic < 1) was
      eucalyptus, rosemary, and mineral oils (volume ratio 4:4:2) without patchouli,
      pine or cajuput oils added, while most preparations showed an antagonistic
      anticandidal effect (Sigmafic > 1). The blended essential oil preparations were
      characterized for their components by GC/MS, and contained 1,8-cineole as a major
      component. However, the preparation containing the highest amount of 1,8-cineole
      did not exhibit the best synergistic effect, which was shown by the preparation
      comprising the highest amount of alpha-pinene. Hence, we concluded that the
      differential antibacterial effect of either blended oil preparations or
      single/pure essential oils was influenced by the amount of alpha-pinene and the
      number of active components in either the blended preparations or single/pure
      essential oils.

PMID- 27032219
TI  - Medication Reconciliation.

PMID- 27032220
TI  - Pill use before or during pregnancy does not raise risk of birth defects.

PMID- 27032221
TI  - Optimising the management of polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) is the most common inherited renal disorder that
      results in chronic kidney disease. PKD has an autosomal dominant pattern of
      inheritance. The prevalence is between 1:500 and 1:1,000. Up to 10% of adults
      with end-stage renal disease (ESRD) have a genetic disorder such as PKD. A family
      history of PKD may be absent in up to 25% of affected individuals. The most
      common clinical features are visible haematuria, loin pain, UTI and hypertension.
      The typical clinical course is a progressive increase in the number and size of
      renal cysts associated with gradual loss of kidney function (falling eGFR). Risk
      factors for progression include: younger age at diagnosis; large kidney volume;
      rapid cyst growth; hypertension; male gender; and visible haematuria.
      Approximately 50% of individuals with PKD will require renal replacement therapy
      by the sixth decade of life. PKD is a multisystem disorder associated with
      multiple bilateral renal cysts, slowly increasing kidney size and progressive
      chronic kidney disease. Diagnosis of PKD is confirmed by ultrasound showing the
      presence of multiple kidney cysts. More than 80% will also have multiple liver
      cysts, which can lead to local pressure effects. Cerebral haemorrhage, secondary
      to rupture of a berry aneurysm, occurs in up to 8% of individuals. Mitral valve
      prolapse occurs in up to 25% of patients.

PMID- 27032222
TI  - Managing acute and chronic renal stone disease.
AB  - Nephrolithiasis, or renal stone disease, is common and the incidence is
      increasing globally. In the UK the lifetime risk is estimated to be 8-10%. On a
      population level, the increase in stone incidence, erosion of gender disparity,
      and younger age of onset is likely to reflect increasing prevalence of obesity
      and a Western diet with a high intake of animal protein and salt. Stones can be
      detected by a variety of imaging techniques. The gold standard is a non-contrast
      CT of kidneys, ureters and bladder (CT KUB) which can identify > 99% of stones.
      CT KUB should be the primary mode of imaging for all patients with colic unless
      contraindicated. In such instances, or if a CT KUB is not available, an
      ultrasound KUB is an alternative. This has advantages in terms of radiation
      exposure and cost, but is limited in sensitivity, particularly for ureteric
      stones. Once diagnosed, a plain film KUB can be used for follow-up of radiopaque
      stones. For most patients diclofenac is a reasonable first choice of analgesia,
      e.g. 50-100 mg rectally, or 75 mg IM. Opioid medication can worsen nausea and be
      less effective, but should be used if there is a contraindication to NSAIDs. A
      combination of diclofenac, paracetamol, and/or codeine regularly can provide
      adequate pain control in many cases. Failure of this analgesic combination should
      prompt consideration of secondary care support. If a ureteric stone < 5 mm in
      diameter is identified, the expectation is that this will pass without
      intervention. Initially medical management is still useful for stones between 5
      and 10mm in diameter, but urology input is more likely to be necessary as up to
      50% of these may require intervention. Stones that are >10 mm in diameter should
      be discussed with the urology service as they are unlikely to pass spontaneously.

PMID- 27032223
TI  - Tailor systemic therapy to the patient with severe psoriasis.
AB  - There is no standard definition regarding the severity of psoriasis, and a number
      of factors should be considered, including the extent and stability of skin
      disease, involvement of joints, response to treatment, and impact on quality of
      life. Erythrodermic psoriasis and pustular psoriasis are severe conditions and
      the patient may be systemically unwell and febrile. NICE recommends that four key
      areas should be evaluated and recorded when assessing patients: severity, using
      the static Physician's Global Assessment (sPGA); disease impact on physical,
      psychological and social wellbeing using the Dermatology Life Quality Index
      (DLQI); the presence of psoriatic arthritis; and comorbidities. Ideally, patients
      should be assessed annually for psoriatic arthritis: the Psoriasis Epidemiology
      Screening Tool is a validated tool to screen for psoriatic arthritis in primary
      and secondary care. Patients with severe psoriasis should undergo cardiovascular
      risk assessment at presentation and every five years, or more frequently if
      indicated. Referral to secondary care should be made for patients with any type
      of psoriasis with poor response to topical therapy (after 2 or 3 months according
      to SIGN) and for extensive psoriasis. Cases where the psoriasis is having a
      significant physical or psychological impact on an individual's quality of life
      warrant early referral, as do those where the diagnosis is uncertain. Patients
      with generalised pustular psoriasis or erythroderma should be referred urgently
      for same-day specialist input. Patients with acute guttate psoriasis who may
      require phototherapy should also be referred. Children and adolescents with any
      type of psoriasis should be referred to a specialist at initial presentation.

PMID- 27032224
TI  - Inherited disorders.

PMID- 27032225
TI  - TREATMENT OF WAR NEUROSES. 1916.

PMID- 27032226
TI  - Communication skills are as important as diagnostic skills.

PMID- 27032227
TI  - [ACTIVATION OF PERIPHERAL NATURAL KILLER CELLS IN WOMEN WITH REPEATED EARLY
      PREGNANCY LOSS].
AB  - The increased number of peripheral blood NK (pNK) cells has been discussed as a
      factor for embryo implantation failure and early pregnancy loss. However, the
      assessment of activated pNK cells with increased cytotoxic activity could be a
      distinct marker for immune dysregulation leading to pregnancy complications. CD69
      membrane receptor expression has been measured by flow cytometry in different
      subtypes of pNK cells in 55 women with two or more pregnancy loss between six and
      twelve week of gestation with absence of any hormonal, anatomical or inherited
      cause for pregnancy loss and in 43 healthy women with at least one delivery at
      term and no history for reproductive failure. Increased expression of CD69 in
      CD56 positive pNK cells was found in the study group compared to controls (12.2%
      versus 6.5%, p<0.005). In addition, the subpopulation of CD56dim and
      CD56brightpNK cells in women with recurrent pregnancy loss showed increased
      percent of CD69 activation marker expression compared to controls (respectively
      13.2% versus 7.2 p<0.005; and 4.6% versus 3.1% p=0.04). CD56brightCD16negative
      pNK cells (identical with those in uterine endometrium) in the investigated group
      has been found with higher CD69 expression compared to controls (3.3% versus
      1.7%, p=0.03). Primary dysregulation in NK cells activity could be supposed in
      women with repeated early pregnancy loss without another underlined pathology.
      Investigation of active status of NK cells but not only NK cell count could be
      evaluation marker of impaired immunology regulation in early pregnancy
      development.

PMID- 27032228
TI  - [SOME DIAGNOSTIC ASPECTS OF CHLAMYDIA TRACHOMATIS UROGENITAL INFECTIONS].
AB  - The following tests were used to make the diagnosis of Chlamydia Trachomatis:
      Ensime Immunoassay (EIA), Enzyme-Linked FluorescentAssay (ELFA), Polymerase Chain
      Reaction DNA amplification for Chlamydia Trachomatis, Neisseria Gonorrhoeae,
      Mycoplasma Genitalium and Ureaplasma Urealyticum. The subject of this study were
      486 outpatients between the ages of 17 and 62, diagnosed with urethritis,
      epidydimitis, prostatitis, cervicitis, endocervicitis, pelvic inflammatory
      disease and sterility. Comparison PCR and EIA showed statistically significant
      difference between the positive results obtained by the two methods (p<0.001).
      Comparing PCR and ELFA on the other hand, did not show any statistically
      significant difference (p>0.1). EIA is the method that gives a higher percentage
      of nonspecific positive reactions, while the results obtained with ELFA are much
      closer to the ones obtained by PCR. According to contemporary evidence based
      medicine, the development of unified standart methods for diagnosis and
      evaluation is of vital importance, not only for the patient and the treating
      physician but also concerns for the healthcare system, the general public and the
      pharmaceutical companies as well.

PMID- 27032229
TI  - [MANAGEMENT OF PLACENTA ACCRETA, DIAGNOSED BEFORE BIRTH].
AB  - The optimal management of placenta accreta and until now remains unclear. The
      reasons for this are a rarity of this condition and the considerable
      heterogeneity of the group under the term "placenta accreta." Total hysterectomy
      during caesarean section is the most common approach to a known placenta accreta.
      Planned or emergency perinatal hysterectomy is associated with several
      complications--damage to the urinary tract, relaparotomiya, massive blood
      transfusions and stay in ICU. The average blood loss is about 3000 ml. To reduce
      blood loss in perinatal hysterectomy contribute: preliminary uterine artery
      occlusion, istmus-coporal longitudinal hysterectomy for extraction of the fetus,
      placental extraction along with the uterus. To save the woman's uterus at
      placenta accreta are using the following methods: cutting the uterine wall on
      which is located the placenta, imposing single stitches covering 2-3 cm in 1 cm,
      around the placental area; removal of the maximum possible part of the placenta;
      using longitudinal hysterectomy. So far, there are no comparative studies of the
      efficacy of different surgical techniques to preserve the uterus cases of
      placenta accreta. Extraction of the placenta to be done after the administration
      of uterotonics and devascularization the uterus. To reduce bleeding from the
      uterus after removal of parts of the placenta and according to the situation can
      be used: x-back hemostatic sutures from internal side of the uterus, tamponade
      with gauze roll, balloon catheters or haemostatic mushrooms. Conservative
      surgical treatment of placenta accreta is not always possible. In hospital
      Maternity Hospital-Sofia for the period 1986-2000 there were 17 cases of placenta
      accreta diagnosed only at birth. Maintaining the uterus was successful in 35% of
      these cases.

PMID- 27032230
TI  - [COMPLICATIONS OF DIAGNOSTIC AND OPERATIVE HYSTEROSCOPY--REVIEW].
AB  - Hysteroscopy is a diagnostic or surgical mini-Invasive gynecologic operating
      procedure. The complications of this standard procedure are relatively rare.
      According to retrospective studies they are 0.95-13.6%. They occur more often by
      an operative rather than a diagnostic hysteroscopy. These complications could be
      divided into two groups of an approximately equal occurrence--due to a dilation
      and passing through the cervix uteri (cervical laceration, creative a false
      cervix uteri, perforation, bleeding, impossibility to pass through the inner
      orifice of the cervical canal, insufficiency of the cervix uteri) and due to the
      operative technique itself (uterine perforation, fluid overload, thermal or
      mechanical trauma of the inner urinaiy and gastrointestinal tract, infection,
      rupture of the uterus during a subsequent pregnancy). The most occurring
      complication is namely the uterine perforation--1-9%, the most severe could
      indeed be the fluid overload--0.01-11%. The gynecologist performing the
      hysteroscopy should be well grounded in the typical complications. Unveiling and
      performing a quick intervention of the latter could prevent unwanted consequences
      for the patient and the legal issues that could follow occur.

PMID- 27032231
TI  - [LAPAROSCOPIC SACROCOLPOPEXY].
AB  - Numerous surgical procedures have been described for the management of pelvic
      organ prolapse. Laparoscopic sacrocolpopexy has evolved from classical abdominal
      sacrocolpopexy and provides the potential to combine the success rate of an
      abdominal approach with faster recovery time associated with a minimally invasive
      technique. Pelvic organ support was assessed objectively using the pelvic organ
      prolapse quantification scale (POP-Q). Tissue dissection and mesh placement are
      facilitated by magnification of the operating field using laparoscopic approach.
      Our results confirm previous findings that laparoscopic sacrocolpopexy is a safe
      and efficacious surgical treatment for pelvic organ prolapse. It provides
      excellent support and good functional outcome with overall improvement in sexual
      function.

PMID- 27032232
TI  - [FETAL PROGRAMMING OF METABOLIC DISORDERS].
AB  - Our knowledge of fetal programming has developed notably over the years and
      recent data suggest that an unbalanced diet prior and during pregnancy can have
      early-onset and long-lasting consequences on the health of the offspring.
      Specific negative influences of high dietary glucose and lipid consumption, as
      well as undernutrition, are associated with development of metabolic syndrome,
      insulin resistance and diabetes in the offspring. The mechanisms underlying the
      effects of maternal hyperglycemia on the fetus may involve structural, metabolic
      and epigenetic changes. The aim of this review is to illustrate how adverse
      intrauterine environment may influence molecular modifications in the fetus and
      cause epigenetic alterations in particular. It has been demonstrated that
      prenatal epigenetic modifications may be linked to the pathogenesis and
      progression of the adult chronic disorders. Studies on epigenetic alterations
      will contribute to a better understanding of the long-term effects of in utero
      exposure and may open new perspectives for disease prevention and treatment.

PMID- 27032233
TI  - [INTRODUCTION OF ENDOSCOPIC LASER THERAPY FOR COMPLICATED MONOCHORIONIC TWINS IN
      BULGARIA].
AB  - OBJECTIVE: The aim of this study is to describe our initial experience of
      endoscopic laser coagulation of inter-twin placental vessels in the treatment for
      severe twin-to-twin transfusion syndrome (TTTS) and selective fetal growth
      restriction (sFGR) at SABBAL "Dr Shterev Hospiat". METHODS: Endoscopic laser
      surgery was carried out in eight cases of TTTS and two cases of sFGR at a median
      gestational age of 21.4 (range 16.4-23.1) weeks. In the group of TTTS there was
      one, three and four cases of Quintero stage 2, 3 and 4, respectively. Both cases
      of sFGR were Gratacos type 2. RESULTS: In the eight cases of TTTS, there was
      survival of both twins in four cases (one, two and one of Quintero stages 2, 3
      and 4, respectively), survival of one twin in one case (Quintero stage 3) and
      death of both twins in three cases (all Quintero stage 4). In the sFGR group,
      both twins survived in one case and one survived in one case. The three cases of
      TTTS with death of both twins were in the first four cases of the series and the
      death occurred during or within 24 hours of the procedure where in 2 cases there
      was SROM with cervical length 7 and 12 mm respectively. In the seven cases with
      survivors, the median gestational age at delivery was 32.3 (range 28.1-37.0)
      weeks. CONCLUSIONS: Our results from endoscopic surgery in TTTS and sFGR are
      encouraging and are likely to improve with increasing experience. There was at
      least one survivor in two of the first four cases and in all six subsequent
      cases.

PMID- 27032234
TI  - [The primary cancer of fallopian tube--a clinical case].
AB  - The primary cancer of the fallopian tube is only 1% of all malignant diseases
      affecting the female genital tract. The etiology is unknown and is assessed with
      untypical symptomatic. It often affects women at age over 50 years old. Recently
      in literature are described about 1200 clinical cases. The primary carcinomaof
      fallopian tube resembles the epithelial ovarian cancers, which defines the
      similarity in the diagnosis, treatment and follow up of the patients with such
      type of pathology. We describe a clinical case of 66 year old woman with primary
      serous low graded cancer of a fallopian tube. The symptoms were presented of dull
      pains in the lower part of the abdomen and a little quantity of free fluid in the
      pelvis. The diagnosis is set after a surgical intervention, based on
      pathoanatomic results. After the radical hysterectomy with bilateral salpingo
      oophorectomy, lymphadenectomy and omentectomy, the patient is treated with
      adjuvant chemotherapy with platinum and taxane.

PMID- 27032235
TI  - [Genital haemorrhage in children and adolescent girls--a management algorythm].

PMID- 27032236
TI  - [CONGENITAL MELANOCYTIC NEVUS OF THE SHOULDER WITH RAPID GROWTH PROGRESSION
      DURING PREGNANCY. SUCCESSFUL SURGICAL APPROACH].
AB  - Congenital melanocytic nevi are common subject of scientific debates nowadays,
      because of their possibility for transformation in malignant melanoma, although
      relatively rare. The diagnosis is difficult, due to their non-specific clinical
      and histological presentation, while the therapeutic methods are varied,
      depending on their size and localization. Surgical excision, however, is the most
      secure among them, because a complete removal of the lesion could be achieved,
      which, firstly provides a prevention of a possible malignant transformation, as
      well as this approach provides material for histological examination. We present
      a case of a 23-year-old female patient with congenital melanocytic nevus, located
      on the upper back, which increased significantly its size during her pregnancy,
      successfully treated by single surgical excision, with excellent aesthetic
      results.

PMID- 27032237
TI  - STOPPING HACKERS.

PMID- 27032238
TI  - GETTING CLINICAL ANALYTICS BARRIERS TO FALL.

PMID- 27032239
TI  - INTEROPERABILITY INCHES FORWARD.

PMID- 27032240
TI  - PROVIDERS EXTEND CLOUD EMBRACE.

PMID- 27032241
TI  - BIG DATA AS A LIFESAVER.

PMID- 27032242
TI  - A CASE FOR ANALYTIC PROFICIENCY.

PMID- 27032243
TI  - BIG IT CHALLENGES FOR GENOMICS.

PMID- 27032244
TI  - COST-JUSTIFYING SECURITY.

PMID- 27032245
TI  - EHRs and Beyond.

PMID- 27032246
TI  - [THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE
      LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND
      APOC-III].
AB  - According to phylogenetic theory of general pathology, the function of low
      density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the
      effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier
      stages of phylogenesis than functioning of insulin-dependent phylogenetically
      late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and
      HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of
      cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and
      linolenic LDL under the effect of cholesteryl ester transfer protein. It is
      reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic
      VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL
      by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not
      converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than
      oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of
      postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is
      uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL
      These LDL increase plasma contents of TG and LDL-cholesterol and form small dense
      palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in
      nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no
      pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an
      indicator of accumulation of non-physiological palmitic LDL and atherosclerosis
      atheromatosis risk factor ApoE content ofpalmitic LDL increases together with
      apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100
      endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests
      for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL
      by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to
      evaluate the efficiency of atherosclerosis prevention when physiological function
      of trophology and biological reaction of exotrophy are normalized.

PMID- 27032247
TI  - [THE BIOMARKERS FOR TIMELY DIAGNOSTICS OF COLORECTAL CANCER].
AB  - The colorectal cancer (CC) is one of the most widespread type of cancer all over
      the world. It is confirmed that the screening procedures intended for timely
      detection of CC and adenomatous polyps, significantly decrease mortality. The
      colonoscopy and analysis offeces for occult blood are widely applied as screening
      procedures. However, they have a number of shortcomings. The studies of the last
      decade revealed number of genetic and epigenetic markers potentially permitting
      revealing patients with CC at early stages of development of disease. The article
      analyzes CC-specific microRNA and their possible interactions with different
      transcriptional factors. These factors, being integrated into the structure of so
      called network s with direct signal propagation, ensure special stability of all
      regulatory system. The derangement of functioning of these networks quite often
      results in pathological alterations.

PMID- 27032248
TI  - [THE ANALYSIS OF INDICATORS OF MINERAL METABOLISM IN PATIENTS WITH DEGENERATIVE
      DYSTROPHIC AFFECTIONS OF JOINTS].
AB  - The analysis of indicators of mineral metabolism in patients with degenerative
      dystrophic affections of joints demonstrated that under development of
      osteoarthrosis process the alteration of indicators of concentration of
      electrolytes in blood serum, urine and synovial fluid occurs. The stage II of
      process is characterized by maximal alterations of indicators. The indicator of
      relationship between concentration of phosphate-ion and index of phosphatases of
      blood serum turned out the significant coefficient of correlation.

PMID- 27032249
TI  - [THE DIFFERENTIAL DIAGNOSTIC OF ANEMIA].
AB  - The article presents analysis of the publications' data of the recent years
      concerning regulation of iron metabolism and possibilities of application of
      indicators of iron metabolism in differential diagnostic of anemia. The original
      results of protein detection are described concerning bivalent transporter of
      metals and ferroportine under iron-deficiency anemia, anemia of chronic
      inflammatory diseases and autoimmune hemolytic anemia. The significance of these
      proteins in more profound comprehension of pathogenesis is demonstrated

PMID- 27032250
TI  - [THE DIAGNOSTIC VALUE OF MODERN METHODS OF MICROBIOLOGICAL VERIFICATION OF
      COMMUNITY-ACQUIRED PNEUMONIA IN CLINICAL PRACTICE].
AB  - The study was carried out to determine etiological structure and informativeness
      of different methods of detection of agents of community-acquired pneumonia, the
      sampling included 274 examined patients aged from 16 to 80 years with community
      acquired pneumonia of different degree of severity and being under hospital
      treatment. Besides of standard laboratory and clinical methods of examination
      ofpatients with community-acquired pneumonia special techniques of etiological
      verification were applied: molecular genetic analysis (polymerase chain reaction)
      of phlegm, qualitative detection of antigen Legionella pneumophila of serogroup 1
      and antigen Streptococcus pneumoniae in samples of urine using quick immune
      chromatographic test, detection of level of serum specific immunoglobulines class
      M and G to Chlamidophilia pneumoniae, Mycoplasma pListeria monocytogenes in
      dynamics using immunoenzyme technique. The etiological structure of community
      acquired pneumonia was established based of study results. The analysis of
      informativeness of different methods of etiological verification of diagnosis of
      community-acquired pneumonia demonstrated that combination ofpolymerase chain
      reaction and serological method is the optimal one.

PMID- 27032251
TI  - [THE DNA DIAGNOSTIC OF PSEUDOMONAS INFECTION].
AB  - The modern laboratory diagnostic of pseudomonas infection, including
      bacteriologic analysis with subsequent identication of agent, is time-consuming
      and it is not every time effective because of modifiability of characteristics of
      the mentioned agent. The article presents the laboratory mode of identification
      of Pseudomonas aeruginosa based on electrophoresis analysis of DNA isolatedfrom
      wound samples or microbial mass grew on solid nutritional medium. The wound
      sample or pure growth is placed into physiological solution and is warmed under
      990C. This action results in DNA releasing into supernatant which sample is
      underwent to standard horizontal electrophoresis in agarose gel with ethidium
      bromide. The presence on electrophoregrams of three bands of DNA fluorescent in
      ultraviolet with size of fragments about 10,000, 6000-8000a and less than 750
      pairs of nucleotides testifies the presence of P. aeruginosa in the analyzed
      biomaterial. The given mode permits to identify both chromogenic and pigment-free
      strains of P. aeruginosa and to differentiate them of other representatives of
      non-fermentative gram-negative bacteria and most significant genera and species
      of family of Enterobacteriaceae. The identification of P. aeruginosa in wound
      sample using the proposed mode implementing without its bacteriological analysis,
      can be used as technique of express diagnostic of pseudomonas infection.

PMID- 27032252
TI  - [THE HIGHLY EFFECTIVE DETECTION OF DNA RICKETTSIA USING TECHNIQUE OF POLYMERASE
      CHAIN REACTION IN REAL-TIME].
AB  - The article considers development of highly effective technique of detection of
      genetic material of ricketsia based on polymerase chain reaction in real-time
      using original primers to the most conservative sites of gene of citrate synthase
      (gItA). The analytical sensitivity of the developed polymerase chain reaction in
      real-time test permits to detect from 80 genome equivalents in analyzed sample
      during three hours. The high specificity of test-system is substantiated by
      detection of nucleotide sequences of amplificated fragments of gene gltA. The
      approbation ofthe polymerase chain reaction in real-time test is carried out on
      collection of 310 ticks of species I. persulcatus, I. pavlovskyi, D. reticulatus.
      It is demonstrated that the developed alternate ofprimers and probe permits with
      high degree of sensitivity and specifcity to detect DNA of different species of
      ricketsia widespread on territory of Russia (R. sibirica, R. raoultii, R.
      helvetica, R. tarasevichiae). The proposed polymerase chain reaction in real-time
      test can be appliedfor isolation of fragment of gene gltA with purpose for
      detecting nucleotide sequence and subsequent genetic typing of ricketsia. The
      application ofthe proposed technique can facilitate task of monitoring hot spots
      of ricketsiosis.

PMID- 27032253
TI  - [THE COMPARATIVE ANALYSIS OF TECHNIQUES OF IDENTIFICATION OF CORYNEBACTERIUM NON
      DIPHTHERIAE].
AB  - The comparative analysis was carried out concerning effectiveness of three
      techniques of identification of Corynebacterium non diphtheriae: bacteriological,
      molecular genetic (sequenation on 16SpRNA) andmass-spectrometric (MALDI-ToFMS).
      The analysis covered 49 strains of Corynebacterium non diphtheriae
      (C.pseudodiphheriticum, C.amycolatum, C.propinquum, C.falsenii) and 2 strains of
      Corynebacterium diphtheriae isolated under various pathology form urogenital
      tract and upper respiratory ways. The corinbacteria were identified using
      bacteriologic technique, sequenation on 16SpRNA and mass-spectrometric technique
      (MALDIToF MS). The full concordance of results of species' identification was
      marked in 26 (51%) of strains of Corynebacterium non diphtheriae at using three
      analysis techniques; in 43 (84.3%) strains--at comparison of bacteriologic
      technique with sequenation on 16S pRNA and in 29 (57%)--at mass-spectrometric
      analysis and sequenation on 16S pRNA. The bacteriologic technique is effective
      for identification of Corynebacterium diphtheriae. The precise establishment of
      species belonging of corynebacteria with variable biochemical characteristics the
      molecular genetic technique of analysis is to be applied. The mass-spectrometric
      technique (MALDI-ToF MS) requires further renewal of data bases for identifying
      larger spectrum of representatives of genus Corynebacterium.

PMID- 27032254
TI  - [THE CHROMATOGRAPHY-MASS SPECTROMETRY ANALYSIS OF MICROBIAL FATTY ACIDS IN HUMAN
      BIOLOGICAL FLUIDS AND THEIR CLINICAL SIGNIFICANCE].
AB  - The technique of mass-spectrometric microbial markers is known for almost 20
      years. The technique is described in a number of research publications,
      dissertations and methodological literature. It passed the registration in
      Roszdravnadzor and is permitted for implementation as a new medical technology in
      medical institutions on the territory of the Russian Federation ("The evaluation
      of microecological human status using technique of mass-spectrometry" license FS
      No 2010/038 of 24.02.2010). The technique of mass-spectrometric microbial markers
      began to be developed as instrument of clinical routine analysis and monitoring
      of microecological status, infection and disbiosises in clinical and out-patient
      practice. The description of technology of mass- spectrometric microbial markers
      in this aspect requires different than before approach to introduction of
      clinical laboratory assistants and physicians into technique application. The
      substantiation given concerning species specificity of composition of fatty acids
      and (fatty) aldehydes of cellular wall of microorganisms as a basis of their
      species differentiation in pure culture. The choice is explained concerning
      molecular markers for their detection in blood and other clinical material with
      the purpose of further reconstruction of composition of human microbial cenosis
      (microecology) on blood or calculation of composition of mixed infection in
      organs om samples of inflammation focus--urine, liquor, phlegm, exudate,
      drainage, and similar samples containing chemical information about microbes.

PMID- 27032255
TI  - [THE MOLECULAR GENETIC CHARACTERISTIC OF SPECIES CONTENT OF SALIVA AND GINGIVAL
      RECESS UNDER PERIODONTITIS].
AB  - The examination was carried out of samplings of 110 patients with periodontitis
      (observation group) and 60 patients without pathology of periodont (comparison
      group). The polymerase chain reaction was used to analyze samples of saliva and
      contents of periodontal recesses for detecting species-specific DNA fragments of
      Porphymmonas gigngivalis, Streptococcus macacae, S. mutans, S. oralis, S.
      salivarius, S. sangis, S. sobrinus, Treponema denticola. In patients with
      periodontitis S. mutans, S. oralis S. sobrinus were reliably more often detected
      in the content of periodontal recesses and S. mutans, S. sobrinus i in saliva. In
      the observation group the rate of detection of association S. mutans--S. oralis-
      S. sangis--S. sobrinus was significantly exceeded (up to 15.6%, X2 = 9.1, p =
      0.004). In ten days of effective treatment of periodontitis reliable decreastng
      of rate of detection of S. wasoralis, S. sobrinus was observed in contents of
      periodontal recesses but not in of saliva. The detection of S.sobrinus using
      technique of polymerase chain reaction in contents of periodontal recesses and/or
      saliva of patients with periodontitis has a diagnostic value. The detection of
      S.sobrinus in contents of periodontal recesses is significant both in monoculture
      and in association S. mutans--S. oralis--S. sangis--S.sobrinus. The absence of S.
      sobrinus in contents of periodontal recesses testifies effectiveness of treatment
      of main disease (periodontitis).

PMID- 27032256
TI  - [THE CHARACTERISTICS OF MORPHOLOGY OF BIOFILM OF PERIODONTIUM UNDER INFLAMMATORY
      DISEASES OF GUMS (CHRONIC CATARRHAL GINGIVITIS, CHRONIC PERIODONTITIS, CANDIDA
      ASSOCIATED PERIODONTITIS) ACCORDING RESULTS OF ELECTRONIC MICROSCOPY].
AB  - The study was carried out to analyze morphology of biofilm of periodontium and to
      develop electronic microscopic criteria of differentiated diagnostic of
      inflammatory diseases of gums. The scanning electronic microscopy was applied to
      analyze samples of bioflm of periodont from 70 patients. Including ten patients
      with every nosologic form of groups with chronic catarrhal periodontitis. of
      light, mean and severe degree, chronic catarrhal gingivitis, Candida-associated
      paroperiodontitis and 20 healthy persons with intact periodontium. The analysis
      was implemented using dual-beam scanning electronic microscope Quanta 200 3D (FEI
      company, USA) and walk-through electronic micJEM 100B (JEOL, Japan). To detect
      marker DNA of periodont pathogenic bacteria in analyzed samples the kit of
      reagentsfor polymerase chain reaction "MultiDent-5" ("GenLab", Russia). The
      scanning electronic microscopy in combination with transmission electronic
      microscopy and polymerase chain reaction permits analyzing structure, composition
      and degree of development of biofilm of periodontium and to apply differentiated
      diagnostic of different nosologic forms of inflammatory diseases of periodontium,
      including light form of chronic periodontitis and gingivitis. The electronic
      microscopical indications of diseases ofperiodontium of inflammatory character
      are established: catarrhal gingivitis, (coccal morphological alternate), chronic
      periodontitis (bacillary morphological alternate), Candida-associated
      periodontitis (Candida morphological alternate of biofilm ofperiodontium).

PMID- 27032258
TI  - Kinetics and Antioxidant Capacity of Proanthocyanidins Encapsulated in Zein
      Electrospun Fibers by Cyclic Voltammetry.
AB  - The proanthocyanidins encapsulated in zein (zein-PA) fibers was via
      electrospinning technique. The kinetics and antioxidant capacity of PA from zein
      fibers was investigated by cyclic voltammetry. Circular dichroism was used to
      investigate the secondary structure change of zein and its influence on the shape
      of fibers. The addition of PA caused a significant increase in viscosity and made
      fibers wider. These hydrogen bonds between zein and PA molecules would favor the
      alpha-helix change and decrease the beta-folds of zein in electrospinning
      solutions, leading to a round-shaped tendency of fibers and enhancing the thermal
      properties slightly. Zein-PA fibers showed high encapsulation efficiency close to
      100%, and the encapsulated PA retained its antioxidant capacity in fibers. Zein
      PA fibers showed a good controlled release toward PA, and the predominant release
      of PA from fibers was Fickian diffusion, which could be well described by first
      order model and Hixson-Crowell model. 

PMID- 27032257
TI  - Hyperoside nanocrystals for HBV treatment: process optimization, in vitro and in
      vivo evaluation.
AB  - The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its
      dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals
      were prepared using high pressure homogenization technique followed by
      lyophilization. A Box-Behnken design approach was employed for process
      optimization. The physicochemical properties, pharmacokinetics and anti-HBV
      activity in vivo of Hyp nanocrystal prepared with the optimized formulation were
      systematically investigated. Hyp nanocrystals prepared with the optimized
      formulation was found to be rod shaped with particle size of 384 +/- 21 nm and
      PDI of 0.172 +/- 0.027. XRPD studies suggested slight crystalline change in drug.
      Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure
      Hyp. The nanocrystals exhibited enhanced Cmax (7.42 +/- 0.73 versus 3.80 +/- 0.66
      mg/L) and AUC0 - t (193.61 +/- 16.30 versus 91.92 +/- 17.95 mg.h/L) with a
      210.63% increase in relative bioavailability. Hyp nanocrystals exhibited
      significantly greater anti-HBV activity than Hyp. These results suggested that
      the developed nanocrystals formulation had a great potential as a viable approach
      to enhance the bioavailability of Hyp. 

PMID- 27032259
TI  - No mystery to revalidation.

PMID- 27032260
TI  - Government wants 'honest' nurses to be treated more leniently.

PMID- 27032262
TI  - Nurses in England will receive 1% pay rise starting this month.

PMID- 27032264
TI  - NHS England wants all GP referrals to be electronic by 2018.

PMID- 27032265
TI  - Trust appoints 30 matrons to provide hands-on care.

PMID- 27032267
TI  - Three quarters of staff work overtime.

PMID- 27032268
TI  - Why research is vital.

PMID- 27032269
TI  - Full steam ahead.

PMID- 27032270
TI  - Listening to feedback.

PMID- 27032273
TI  - Board's eye view - Being in the moment.

PMID- 27032284
TI  - Revalidation and reflective practice.
AB  - From April 2016 nurses must meet the requirements of the new Nursing and
      Midwifery Council (NMC) revalidation process to maintain their registration. It
      is their responsibility to ensure they meet all revalidation requirements, but
      organisations and nurse leaders can support them to do so. Reflection is an
      important part of revalidation, and nurses are required to submit written
      reflective accounts and engage in reflective discussion. This article discusses
      how revalidation encourages a more conscious and active form of reflection. It
      also describes how leaders can help nurses to reflect on practice to identify
      improvements and become more familiar with the NMC Code. 

PMID- 27032285
TI  - Helping nurses through the revalidation process.
AB  - Revalidation can seem challenging for some nurses and managers, but with the
      support of their organisations they can engage confidently with the process. This
      article describes Bupa's approach to creating an infrastructure that embeds
      revalidation in its services. This includes letting nurse leaders know so that
      they can help nurses through the process, and developing a pathway that supports
      nurses' ongoing learning and development. 

PMID- 27032286
TI  - Enhancing nursing students' education by coaching mentors.
AB  - To address some of the recommendations of the Willis Commission ( Royal College
      of Nursing 2012 ), and in response to local evaluation of mentor and nursing
      student experiences, the University of East Anglia has implemented a project to
      teach mentors coaching skills. The aim is to enhance mentor support of nursing
      students during practice placements and improve student learning in practice.
      This article describes the project and discusses the similarities and differences
      between mentoring and coaching. It shows how coaching has reduced the 'burden' of
      mentoring by reducing mentors' workloads, and has helped students to take
      responsibility for identifying learning needs and delivering supervised patient
      care. 

PMID- 27032287
TI  - Nurses' perceptions and experiences of mentoring.
AB  - Pre-registration education programmes provide nursing students with the skills
      and knowledge to become safe and proficient practitioners. Assessment of
      students' competence is a fundamental part of these programmes and mentors play a
      crucial role. Mentors are registered nurses who have completed an appropriate
      mentorship programme in an approved higher education institution, and their main
      role includes teaching, supervising and assessing students' clinical competence.
      The role can be demanding and stressful, and mentors must maintain their
      workloads while supporting students. This article reports the results of the
      qualitative findings of a survey of mentorship practices ( Brown et al 2012 ).
      The findings suggest that mentors value support from link lecturers and practice
      education facilitators, especially when they experience difficulties with nursing
      students who do not have the required competencies to pass their placement. 

PMID- 27032288
TI  - Inspired by patients.

PMID- 27032289
TI  - Concessive and semifactual interpretations during reasoning with multiple
      conditionals.
AB  - The present research evaluates how people integrate factual 'if then' and
      semifactual 'even if' conditional premises in an inference task. The theory of
      mental models establishes that semifactual statements are represented by two
      mental models with different epistemic status: 'A & B' is conjectured and 'not-A
      & B' is presupposed. However, following the principle of cognitive economy in
      tasks with a high working memory load such as reasoning with multiple
      conditionals, people could simplify the deduction process in two ways, by
      discarding: (a) the presupposed case and/or (b) the epistemic status information.
      In Experiment 1 and Experiment 2, we evaluated each of these hypotheses. In
      Experiment 1, participants make inferences from two conditionals: two factual
      conditionals or one factual and one semifactual, with different representations.
      In Experiment 2, participants make inferences with a factual conditional followed
      by two different semifactual conditionals that share the same representations but
      differ in their epistemic status. Accuracy and latency data suggest that people
      think of both the conjectured and the presupposed situations, but do not codify
      the epistemic status of either when the task does not require it. The results are
      discussed through theoretical predictions about how people make inferences from
      different connected conditionals.

PMID- 27032290
TI  - Mitochondrial disease-related mutations at the cytochrome b-iron-sulfur protein
      (ISP) interface: Molecular effects on the large-scale motion of ISP and
      superoxide generation studied in Rhodobacter capsulatus cytochrome bc1.
AB  - One of the important elements of operation of cytochrome bc1 (mitochondrial
      respiratory complex III) is a large scale movement of the head domain of iron
      sulfur protein (ISP-HD), which connects the quinol oxidation site (Qo) located
      within the cytochrome b, with the outermost heme c(1) of cytochrome c(1). Several
      mitochondrial disease-related mutations in cytochrome b are located at the
      cytochrome b-ISP-HD interface, thus their molecular effects can be associated
      with altered motion of ISP-HD. Using purple bacterial model, we recently showed
      that one of such mutations - G167P shifts the equilibrium position of ISP-HD
      towards positions remote from the Qo site as compared to the native enzyme [Borek
      et al., J. Biol. Chem. 290 (2015) 23781-23792]. This resulted in the enhanced
      propensity of the mutant to generate reactive oxygen species (ROS) which was
      explained on the basis of the model evoking "semireverse" electron transfer from
      heme bL to quinone. Here we examine another mutation from that group - G332D
      (G290D in human), finding that it also shifts the equilibrium position of ISP-HD
      in the same direction, however displays less of the enhancement in ROS
      production. We provide spectroscopic indication that G332D might affect the
      electrostatics of interaction between cytochrome b and ISP-HD. This effect, in
      light of the measured enzymatic activities and electron transfer rates, appears
      to be less severe than structural distortion caused by proline in G167P mutant.
      Comparative analysis of the effects of G332D and G167P confirms a general
      prediction that mutations located at the cytochrome b-ISP-HD interface influence
      the motion of ISP-HD and indicates that "pushing" ISP-HD away from the Qo site is
      the most likely outcome of this influence. It can also be predicted that an
      increase in ROS production associated with the "pushing" effect is quite
      sensitive to overall severity of this change with more active mutants being
      generally more protected against elevated ROS. This article is part of a Special
      Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del
      Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

PMID- 27032291
TI  - Erratum.

PMID- 27032292
TI  - Thermodynamics of the formation of Ag(I)-mediated azole base pairs in DNA
      duplexes.
AB  - Isothermal titration calorimetry was applied to determine the thermodynamic
      parameters for the specific binding of Ag(I) ions to a series of DNA duplexes
      comprising Im:Im or Tr:Tr mispairs to form metal-mediated Im-Ag(I)-Im or Tr-Ag(I)
      Tr base pairs (Im=imidazole nucleoside; Tr=1.2,4-triazole nucleoside). A total of
      seven different duplexes are discussed, incorporating one to three artificial
      base pairs in neighboring or non-neighboring positions. The association constant
      related to the formation of Tr-Ag(I)-Tr base pairs is estimated to be <10(3)M(
      1). In contrast, Im-Ag(I)-Im base pairs are much more stable. The intrinsic
      association constant for their formation is in the order of 10(6)M(-1) and is
      therefore larger than that for the formation of T-Hg(II)-T and C-Ag(I)-C base
      pairs consisting of natural nucleobases. Two neighboring Im-Ag(I)-Im base pairs
      form cooperatively, whereas two remotely located Im-Ag(I)-Im base pairs form non
      cooperatively. In general, the specific binding of Ag(I) to Im:Im-containing
      duplexes is enthalpically driven, with a significant additional entropic
      contribution in most cases.

PMID- 27032293
TI  - Concurrent progressive-ratio and fixed-ratio schedule performance under geometric
      and arithmetic progressions by brushtail possums.
AB  - The aim of this study was to compare the demand for food under concurrent
      progressive- and fixed-ratio schedules. Twelve brushtail possums participated in
      16 conditions where schedule, progression and food type were varied. An
      incrementing schedule increased the fixed-ratio requirement within and across
      sessions and was arranged as either a geometric sequence (base 2), or an
      arithmetic sequence (step 5). Two foods were tested: a flaked barley and coco
      pop((r)) mix versus rolled oats. Overall, performance was similar for most
      possums in the within- and across-session incrementing schedules. An analysis of
      the estimates of essential value and break point produced the same account of
      demand for foods under the geometric or arithmetic progressions and within- and
      across-session procedures for 8 of 12 possums. Six possums showed higher demand
      for rolled oats compared to flaked barley, and two possums showed higher demand
      for flaked barley compared to rolled oats. Incrementing ratios within, rather
      than between sessions using an arithmetic progression was demonstrated to be a
      time efficient procedure for investigating demand for different food types
      without affecting conclusions about the relative demand for those foods. 

PMID- 27032294
TI  - Validation of a model of family caregiver communication types and related
      caregiver outcomes.
AB  - OBJECTIVE: Caring for the family is included as one of the eight domains of
      quality palliative care, calling attention to the importance of the family system
      and family communications about cancer during care and treatment of the disease.
      Previously, a model of family caregiver communication defined four caregiver
      communication types-Manager, Carrier, Partner, Lone-each with a unique
      communication pattern. The purpose of the present study was to extend the model
      of family caregiver communication in cancer care to further understand the impact
      of family communication burden on caregiving outcomes. METHOD: This mixed-method
      study employed fieldnotes from a family caregiver intervention focused on quality
      of life and self-reported caregiver communication items to identify a specific
      family caregiver type. Caregiver types were then analyzed using outcome measures
      on psychological distress, skills preparedness, family inventory of needs, and
      quality-of-life domains. RESULTS: Corroboration between fieldnotes and self
      reported communication for caregivers (n = 21, 16 women, mean age of 53 years)
      revealed a definitive classification of the four caregiver types (Manager = 6,
      Carrier = 5, Partner = 6, Lone = 4). Mean scores on self-reported communication
      items documented different communication patterns congruent with the theoretical
      framework of the model. Variation in caregiver outcomes measures confirmed the
      model of family caregiver communication types. Partner and Lone caregivers
      reported the lowest psychological distress, with Carrier caregivers feeling least
      prepared and Manager caregivers reporting the lowest physical quality of life.
      SIGNIFICANCE OF RESULTS: This study illustrates the impact of family
      communication on caregiving and increases our knowledge and understanding about
      the role of communication in caregiver burden. The research provides the first
      evidence-based validation for a family caregiver communication typology and its
      relationship to caregiver outcomes. Future research is needed to develop and test
      interventions that target specific caregiver types.

PMID- 27032295
TI  - Perioperative and oncologic outcomes of robot-assisted vs. open radical
      cystectomy in bladder cancer patients: A comparison of two high-volume referral
      centers.
AB  - OBJECTIVES: To examine perioperative and oncologic outcomes of open (ORC) and
      robot-assisted radical cystectomy (RARC) in bladder cancer (BCa) patients.
      METHODS AND MATERIALS: 368 consecutive patients with cT1-4 M0 BCa treated at two
      high-volume European centers between 2004 and 2013 were evaluated. Data on
      complications, operative time, blood loss, postoperative transfusion,
      reoperation, length of stay (LOS), positive margins, recurrence, cancer-specific
      mortality (CSM), and overall survival were evaluated. Uni- and multivariable
      regression analyses tested the impact of the surgical approach on perioperative
      and oncologic outcomes. RESULTS: Overall, 230 (62.5%) and 138 (37.5%) patients
      were treated with ORC and RARC. In multivariable analyses RARC patients had
      higher odds of prolonged operative time and low-grade complications (all P <=
      0.001). Patients treated with ORC had higher odds of blood loss >500 ml and
      prolonged LOS (all P <= 0.03). No differences were observed in high-grade
      complications and positive margins (all P >= 0.06). No differences were observed
      in 5-year recurrence-free and CSM-free survival rates between patients treated
      with ORC vs. RARC (57.1 vs. 54.2% and 61.9 vs. 73.5%; all P >= 0.3). This was
      confirmed in multivariable analyses, where the surgical approach was not
      associated with the risk of recurrence and CSM (all P >= 0.1). CONCLUSIONS:
      Although ORC might be associated with a shorter operative time, RARC led to lower
      blood loss and shorter LOS. No differences exist in high-grade complications and
      positive margins. RARC and ORC provide similar oncologic control.

PMID- 27032296
TI  - Outpatient Robotic Radical Prostatectomy: Matched-Pair Comparison with Inpatient
      Surgery.
AB  - PURPOSE: To evaluate our initial experience with outpatient robotic radical
      prostatectomy (RRP) and to prospectively compare outcomes with an inpatient RRP
      group. MATERIALS AND METHODS: We conducted a prospective study on 30 carefully
      selected, motivated patients consenting for outpatient RRP (2011-2013). Inclusion
      criteria comprised age<65 years, American Society of Anesthesiologists score<3,
      body mass index<35 kg/m2, localized prostate cancer, and primary treatment.
      Postoperatively, close monitoring was conducted by telephone for the first 24
      hours, with routine follow-up subsequently. This outpatient group was
      prospectively matched 1:1 with a concurrent inpatient RRP group who satisfied
      inclusion criteria for, but did not undergo, outpatient RRP. Validated
      questionnaires were administered prospectively to determine patient satisfaction
      and functional outcomes. RESULTS: All outpatient RRP procedures were performed
      effectively. Twenty-six patients (87%) were discharged the same day of surgery,
      four stayed overnight for various reasons. On comparing outpatient and inpatient
      groups, there were no significant demographic or perioperative differences,
      except for shorter hospital stay (14 hours vs 44 hours, p<0.01). In both groups,
      92% of patients were completely continent (no pads) at 2 months follow-up. Time
      to complete continence in the outpatient and inpatient groups was 32 days vs 43
      days (p=0.09). Validated questionnaires revealed both groups were comparable as
      regards patient/family satisfaction, days of narcotic usage, days to return to
      work, and days to feeling 100% recovered. CONCLUSION: Our initial experience with
      outpatient RRP is promising. Outpatient RRP is associated with excellent patient
      satisfaction and functional outcomes comparable with inpatient RRP. Patient
      motivation and preoperative counseling are vital for success.

PMID- 27032297
TI  - Eosinophilia prevalence and related factors in travel and immigrants of the
      network +REDIVI.
AB  - The population movements during the last decades have resulted in a progressively
      increasing interest in certain infectious diseases. Eosinophilia is a common
      finding in immigrants and travellers. One of the most common causes of
      eosinophilia is helminth infection, and some intestinal protozoa. The aim of this
      paper is to describe the epidemiological characteristics of cases with
      eosinophilia and its association with the presence of parasites in the REDIVI
      data network. This is a multicentre prospective observational study that includes
      patients diagnosed with eosinophilia registered in the cooperative network for
      the study of infectious diseases in travellers and immigrants (+REDIVI) from
      January 2009 to December 2012. A total of 5,255 episodes were recorded in the
      network during the study period, and eosinophilia was observed in 8.1-31.3% of
      cases (depending on the immigration group). There were 60.2% men, with a median
      age of 31years. There were 72.4% immigrants, and 81.2% were asymptomatic. The
      most commonly identified parasites were S.stercoralis (34.4%), Schistosoma sp.
      (11.0%), and hookworm (8.6%). The relationship between eosinophilia and parasite
      infection was significant for all helminths (except for cutaneous larva migrans).
      The symptoms and duration of the journey did not significantly determine the
      presence of eosinophilia. In the case of eosinophilia in a person who has lived
      in helminth endemic areas, it is advisable to carry out targeted studies to
      diagnose the infection, regardless of immigration type, length of stay, or the
      presence of symptoms.

PMID- 27032298
TI  - An outbreak of acute norovirus gastroenteritis in a boarding school in Zamora,
      Spain.

PMID- 27032299
TI  - Developmental proteome dynamics of silk glands in the 5th instar larval stage of
      Bombyx mori L (CSR2*CSR4).
AB  - Bivoltine breed of Bombyx mori (B. mori), CSR2*CSR4 is an Indian high yielding
      silkworm strain. Silk gland proteome of this strain was not studied till now.
      Methods of improving silk production by chemical approaches have reached
      saturation and transgenic methods are needed in further to boost silk production.
      An understanding of proteomic changes during silk gland development helps in
      designing experiments to enhance silk production by transgenic approaches. The
      present study reports comprehensive developmental proteomic analysis of
      CSR2*CSR4, 5th instar whole silk glands. Eighty six unique protein IDs were
      obtained from the analysis of one hundred and twenty protein spots. Among the
      identified proteins, majority of the proteins were involved in metabolism (41%)
      followed by proteins involved in protein homeostasis (30%). Sixty percent of the
      identified proteins showed dynamic nature by expression analysis from day 1, day
      3, day 5 and day 7 gels. In comparison to the published data till now on silk
      gland proteomics this study reports identification of 20 new proteins from the
      silk glands for the first time. SIGNIFICANCE: The paper reports for the first
      time proteomic analysis of high yielding silkworm strain of India. The study
      analyzes whole silk glands to understand the tissue in total during 5th instar
      development. Lowering fibroin content made us to identify a large number of new
      proteins which were not reported till now in the silk gland proteome. Proteins
      which are involved in silk synthesis and release were found to be developmentally
      regulated. The study identified alanine, serine and glycine tRNA ligases for the
      first time and also showed their up-regulation on day 7 of 5th instar larval
      stage. The amino acid repeat of fibroin protein is enriched with the three amino
      acids, glycine, serine and alanine. The identified proteins could be studied
      further to understand their functional role in-depth.

PMID- 27032300
TI  - Inflammatory breast cancer: a new approach.

PMID- 27032301
TI  - Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative
      inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study.
AB  - BACKGROUND: Addition of bevacizumab to standard chemotherapy in the neoadjuvant
      setting in patients with HER2-negative metastatic breast cancer improves
      progression-free survival and the proportion of patients achieving pathological
      complete response. In the BEVERLY-1 (UCBG-0802) trial we aimed to assess the
      addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment
      of patients with HER2-negative inflammatory breast cancer. METHODS: We did this
      phase 2, single-arm trial at 20 hospitals in France. We enrolled women aged 18
      years or older who had non-metastatic HER2-negative inflammatory breast cancer.
      Patients underwent 3-week treatment cycles, receiving neoadjuvant intravenous
      fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), cyclophosphamide (500
      mg/m(2)), and bevacizumab (15 mg/kg) during cycles 1-4, then docetaxel (100
      mg/m(2)) and bevacizumab during cycles 5-8. 2-4 weeks after surgery, patients
      received adjuvant radiotherapy, hormone therapy (if they had a hormone receptor
      positive tumour), and adjuvant intravenous bevacizumab. The primary endpoint was
      pathological complete response in breast and axillary lymph nodes after
      neoadjuvant treatment, determined after centralised review in accordance with
      Sataloff classification and assessed in the intention-to-treat population. Our
      analysis of toxic effects included all patients who received at least one dose of
      bevacizumab. The trial is complete and follow-up is ongoing. This study is
      registered with ClinicalTrials.gov, number NCT00820547. FINDINGS: Between Jan 16,
      2009, and Sept 8, 2010, we enrolled 101 patients, one of whom withdrew consent
      before treatment, leaving 100 patients in the primary endpoint analysis. After
      neoadjuvant therapy, 19 (19% [95% CI 12-28]; p=0.16) of 100 patients achieved a
      pathological complete response according to centralised review. The most frequent
      grade 3-4 events during the neoadjuvant phase were neutropenia (89 [89%] of 100
      patients), febrile neutropenia (37 [37%]), and mucositis (23 [23%]) and during
      the adjuvant phase the most frequent grade 3-4 adverse event was proteinuria (5
      [7%] of 75 patients). One (1%) patient died of thrombotic microangiopathy after
      cycle 1, which was thought to be related to bevacizumab. Two patients (3%)
      developed transitory heart failure. 48 (48%) patients had serious adverse events,
      the most frequent of which was febrile neutropenia (28 [28%]). INTERPRETATION:
      Our results suggest that the addition of bevacizumab to neoadjuvant and adjuvant
      chemotherapy does not provide clinical benefit to patients with non-metastatic
      HER2-negative inflammatory breast cancer. Longer follow-up and correlative
      studies to identify patients who might benefit from bevacizumab are needed.
      FUNDING: Roche, La Ligue Nationale contre le Cancer, UNICANCER, and Chugai
      Pharma.

PMID- 27032302
TI  - Gender and Graft-versus-Host Disease after Hematopoietic Stem Cell
      Transplantation.

PMID- 27032303
TI  - [What's next in glioblastoma treatment: Tumor-targeted or immune-targeted
      therapies?].
AB  - INTRODUCTION: Glioblastoma (GBM) is associated with a poor prognosis. This review
      will discuss different directions of treatment, mostly regarding immunotherapies
      and combinatorial approaches. DEVELOPMENT: Standard treatment for newly diagnosed
      GBM is maximal and safe surgical resection followed by concurrent
      radiochemotherapy (RCT) based on temozolomide, allowing 14.6 months median
      survival. Nowadays, no combination with molecular-targeted therapy had
      significantly improved prognosis. Phases I and II data are emerging, highlighting
      the potential efficacy of associations with other therapies. Studies have
      suggested the potential of targeting tumor stem cells, at less partially
      responsible for resistance to RCT. There is now some evidence that immunotherapy
      is also relevant for brain tumors. Treatment strategies have mainly explored
      vaccines strategies, such as the dendritic cell, heat shock protein or EGFRvIII
      vaccines. Of the work initiated in melanoma, immune checkpoints inhibitors have
      exhibited stimulating results. Others trials have demonstrated potential of
      autologous stimulated lymphocytes. Moreover, strong data indicates that radiation
      therapy has the potential to promote immunogenicity and create a sort of in situ
      personalized vaccine. CONCLUSION: These data provide strong evidence to support
      the potential of associating combinatorial targeted and/or immunotherapeutic
      regimens in patients with GBM that may change patient outcome.

PMID- 27032304
TI  - Frailty prevalence and associated factors in the Mexican health and aging study:
      A comparison of the frailty index and the phenotype.
AB  - BACKGROUND: Frailty is a relatively new phenomenon described mainly in the older
      population. There are a number of different tools that aim at categorizing an
      older adult as frail. Two of the main tools for this purpose are the Fried's
      frailty phenotype (FFP) and the frailty index (FI). The aim of this report is to
      determine the prevalence of frailty and associated factors using both FFP and the
      FI. METHODS: Secondary analysis of 1108 individuals aged 60 or older is
      participating in the third (2012) wave from the Mexican Health and Aging Study
      (MHAS). The FFP and the FI were constructed and a set of variables from different
      domains were used to explore associations. Domains included were: socio
      demographic, health-related, and psychological factors. Regarding prevalence,
      concordance was tested with a kappa statistic. To test significant associations
      when classifying with each of the tools, multiple logistic regression models were
      fitted. RESULTS: Mean (SD) age was 69.8 (7.6) years, and 54.6% (n=606) were
      women. The prevalence of frailty with FFP was 24.9% (n=276) while with FI 27.5%
      (n=305). Kappa statistics for concordance between tools was 0.34 (p<0.001). Age,
      years in school, number of past days in bed due to health problems, number of
      times that consulted a physician last year for health problems, having smoked in
      the past, and life satisfaction were associated with frailty when using any of
      the tools. CONCLUSIONS: There is a persistent heterogeneity on how frailty is
      measured that should be addressed in future research.

PMID- 27032306
TI  - c-Rel in Epidermal Homeostasis: A Spotlight on c-Rel in Cell Cycle Regulation.
AB  - To maintain proper skin barrier function, epidermal homeostasis requires a subtly
      governed balance of proliferating and differentiating keratinocytes. While
      differentiation takes place in the suprabasal layers, proliferation, including
      mitosis, is usually restricted to the basal layer. Only recently identified as an
      important regulator of epidermal homeostasis, c-Rel, an NF-kappaB transcription
      factor subunit, affects the viability and proliferation of epidermal
      keratinocytes. In human keratinocytes, decreased expression of c-Rel causes a
      plethora of dysregulated cellular functions including impaired cell viability,
      increased apoptosis, and abnormalities during mitosis and cell cycle regulation.
      On the other hand, c-Rel shows aberrant expression in many epidermal tumors.
      Here, in the context of its role in different cell types and compared with other
      NF-kappaB subunits, we discuss the putative function of c-Rel as a regulator of
      epidermal homeostasis and mitotic progression. In addition, implications for
      disease pathophysiology with perturbed c-Rel function and abnormal homeostasis,
      such as epidermal carcinogenesis, will be discussed.

PMID- 27032307
TI  - [Not available].

PMID- 27032305
TI  - The Tibetan medicine Zuotai differs from HgCl2 and MeHg in producing liver injury
      in mice.
AB  - Zuotai is composed mainly of beta-HgS, while cinnabar mainly contains alpha-HgS.
      Both forms of HgS are used in traditional medicines and their safety is of
      concern. This study aimed to compare the hepatotoxicity potential of Zuotai and
      alpha-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice
      were orally administrated with Zuotai (30 mg/kg), alpha-HgS (HgS, 30 mg/kg),
      HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene
      expressions related to toxicity, inflammation and Nrf2 were examined. Animal body
      weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg
      produced spotted hepatocyte swelling and inflammation, while such lesions are
      mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in
      HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and
      MeHg increased the expression of liver injury biomarker genes metallothionein-1
      (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth
      response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and
      microphage inflammatory protein (MIP-2), while these changes were insignificant
      in Zuotai and HgS groups. However, all mercury compounds were able to increase
      the Nrf2 pathway genes NAD(P)H: quinone oxidoreductase 1 (Nqo1) and Glutamate
      cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine
      Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2
      and MeHg in hepatic Hg accumulation and toxicological responses.

PMID- 27032308
TI  - [Augmented renal clearance of antibiotics may lead to inadequate dosings for
      patients with sepsis].
AB  - Early, relevant antibiotic treatment is of pivotal significance for survival for
      patients with sepsis. Recent reports reveal, that critically ill patients may
      need substantially higher dosing of antibiotics than the usual standards. The
      background is the newly described augmented renal clearance (ARC), which can be
      observed in critically ill patients with sepsis. ARC results in significantly
      reduced antibiotic concentrations in patients with sepsis and can potentially
      have fatal consequences. The purpose of this paper is to make medical doctors
      aware of the phenomenon and to compensate for the increased antibiotic clearance.

PMID- 27032309
TI  - [Inguinal hernia operation and fertility in men].
AB  - It is still unknown whether or not inguinal hernia repair with or without the use
      of mesh causes infertility in male patients. The objective of this article was to
      discuss the available literature, to ascertain if the preclinical and clinical
      findings point towards a causal relationship. The review showed that the question
      remains difficult to answer due to a limited number of patients included and the
      discordant conclusions drawn in past studies. The largest recent cohort study
      came to the conclusion that there was no clinically significant risk of
      infertility associated with inguinal hernia repair. However, further studies are
      needed. 

PMID- 27032310
TI  - [The use of intermittent pneumatic compression for critical limb ischaemia
      without vascular surgery reconstruction].
AB  - Patients with critical limb ischaemia, without possibility for vascular surgery
      reconstruction, are a high selected population with a wide scale occurrence of co
      morbidity and mortality. We outline the use of intermittent pneumatic compression
      (IPC) to these patients. Impact on both wound healing and cost-effectiveness
      concerning IPC use are recently shown. The overriding purpose of IPC use is to
      decrease the frequency of major and to lower the extent of ischaemic rest pain.
      IPC equipment is currently available around the country, but is not often used on
      the indication critical limb ischaemia. 

PMID- 27032311
TI  - Observation of direction-dependent mechanical properties in the human brain with
      multi-excitation MR elastography.
AB  - Magnetic resonance elastography (MRE) has shown promise in noninvasively
      capturing changes in mechanical properties of the human brain caused by
      neurodegenerative conditions. MRE involves vibrating the brain to generate shear
      waves, imaging those waves with MRI, and solving an inverse problem to determine
      mechanical properties. Despite the known anisotropic nature of brain tissue, the
      inverse problem in brain MRE is based on an isotropic mechanical model. In this
      study, distinct wave patterns are generated in the brain through the use of
      multiple excitation directions in order to characterize the potential impact of
      anisotropic tissue mechanics on isotropic inversion methods. Isotropic inversions
      of two unique displacement fields result in mechanical property maps that vary
      locally in areas of highly aligned white matter. Investigation of the corpus
      callosum, corona radiata, and superior longitudinal fasciculus, three highly
      ordered white matter tracts, revealed differences in estimated properties between
      excitations of up to 33%. Using diffusion tensor imaging to identify dominant
      fiber orientation of bundles, relationships between estimated isotropic
      properties and shear asymmetry are revealed. This study has implications for
      future isotropic and anisotropic MRE studies of white matter tracts in the human
      brain.

PMID- 27032312
TI  - [Is initial success after Monarc((r)) suburethral sling durable at mid-term
      evaluation?].
AB  - OBJECTIVES: Suburethral sling is the gold standard treatment for stress urinary
      incontinence (SUI). Short-term cure rates are high, but only few studies are
      available for longer assessment after transobturator tape procedure. The
      objectives of this study were to assess mid-term functional outcome for
      Monarc((r)) transobturator tape after initial success, and to identify risk
      factors for recurrence. MATERIAL AND METHODS: We conducted a single centre
      retrospective study (2004-2013) on consecutive women with SUI who underwent
      Monarc((r)) transobturator tape procedure and were initially cured at the
      postoperative medical consultation. Pre- and postoperative data (age, weight,
      height, body mass index, hormonal status, surgical history, associated organ
      prolapse [Baden and Walker], associated urinary symptoms, postoperative
      complications [Clavien-Dindo]) were extracted from the electronic medical record.
      Subjective cure was defined by a score of zero from the ICIQ-SF questionnaire, no
      second intervention for recurrent SUI and no need for pads at latest news.
      Statistical analysis was performed using SAS((r)) v9.3 (P<0.05). RESULTS: One
      hundred and thirty-three consecutive women underwent TOT Monarc((r)) procedure,
      and 125 women were cured in the short-term. Among these women, 103 (82%) were
      available for mid-term evaluation. Sixty-four women (62%) had pure stress urinary
      incontinence. The mean follow-up period was 51 months [2-119]. At last follow-up,
      cure rate was 61%. Seventy-eight percent of women with recurrent urinary
      incontinence had SUI. Other women had mixed urinary incontinence (3/40), or de
      novo urgency (6/40). In univariate analysis, we could not identify pejorative
      prognostic factors for mid-term failure. CONCLUSION: In our experience, mid-term
      functional outcome after Monarc((r)) transobturator tape procedure seems to
      deteriorate. After 4 years of follow-up, 61% of the women who were initially
      cured were still free from any leakage. LEVEL OF EVIDENCE: 4.

PMID- 27032313
TI  - [Cryotherapy percutaneous for renal tumors: Our center's beginning experience].
AB  - OBJECTIVE: To evaluate oncologic and functional outcomes after percutaneous
      cryoablation (PCA) for renal masses based on our single center experience.
      PATIENTS AND METHODS: We retrospectively identified 26 patients who underwent PCA
      for 28 tumors between November 2006 and June 2011. Patient's demographics and
      baseline clinical characteristics, tumor features, perioperative information, and
      postoperative outcomes we rerecorded. A biopsy was performed systematically
      before each procedure. Control imaging was obtained at 1, 3, 6 and 12 months, and
      yearly thereafter. Oncological outcomes were determined by radiographic evidence
      of tumor recurrence, which was defined by contrast enhancement at the
      cryoablation site on control imaging at M3. RESULTS: Patients had mean age of
      70.1 years, mean Charlson comorbidity index (CCI) and body mass index) were 6 and
      29 kg/m(2) respectively. There were 11 kidney transplants, including 4 solitary.
      Mean tumor size was 29.5mm and was represented mainly by clear cell renal cell
      carcinomas (16/28), endophytic (17/28) and midkidney (14/28) (+/-9.8). Twenty
      five cryoablations were performed percutaneously by two lumbotomy. Mean clearance
      preoperative MDRD was 66,1 mL/min. Mean length of stay was 3.3 days (+/-2.2).
      Intraoperative complications consisted of 2 pneumothorax and 6 minor
      complications postoperative (Clavien<=2). There were no major complications. Mean
      follow-up was 27.5 months (+/-15.7), MDRD clearance distance was 61.9 mL/min.
      Overall survival and disease-specific survival was 100%, while the recurrence
      free survival was 78.6% (5 recurrences and 1 failure treatment). CONCLUSION: The
      percutaneous cryoablation provides a safe and oncologically to extirpative
      surgery for renal masses in patients with significant medical comorbidities.
      LEVEL OF EVIDENCE: 5.

PMID- 27032314
TI  - Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain,
      cognition and motor function.
AB  - NMDAR antagonism shows analgesic action in humans and animal pain models, but
      disrupts cognitive and motor functions. NMDAR-dependent NO production requires
      tethering of the NMDAR to neuronal NO synthase (nNOS) by the postsynaptic density
      protein-95 (PSD-95). Perturbing the NMDAR/PSD-95/nNOS interaction has therefore
      been proposed as an alternative analgesic mechanism. We recently reported that
      UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier
      permeability, reduced mechanical hypersensitivity in the complete Freund's
      adjuvant (CFA) inflammatory pain model, without disrupting cognitive or motor
      functions. Here, we investigated the analgesic efficacy in the CFA model of
      UCCB01-144, a PSD-95 inhibitor with improved blood-brain-barrier permeability. To
      extend the comparison of UCCB01-125 and UCCB01-144, we also tested both compounds
      in the spared nerve injury (SNI) model of neuropathic pain. Potential cognitive
      effects of UCCB01-144 were examined using the social transmission of food
      preference (STFP) test and the V-maze test, and motor coordination was assessed
      with the rotarod test. UCCB01-144 (10mg/kg) reversed CFA-induced mechanical
      hypersensitivity after 1h, and completely normalised sensitivity after 24h. In
      the SNI model, UCCB01-144 (30mg/kg) partially reversed hypersensitivity after 1h,
      but no effect was observed after 24h. UCCB01-125 did not affect SNI-induced
      hypersensitivity. Rotarod performance was unaffected by UCCB01-144, but 30mg/kg
      UCCB01-144 impaired performance in the STFP test. Collectively, UCCB01-144
      reversed both CFA and SNI-induced hypersensitivity, but the efficacy in the SNI
      model was only transient. This suggests that enhanced BBB permeability of PSD-95
      inhibitors improves the analgesic action in neuropathic pain states. 

PMID- 27032315
TI  - Laparoscopic gastric mobilization and lymphadenectomy during Ivor Lewis
      esophagectomy.

PMID- 27032316
TI  - Isolated injury to the pancreas: The importance of the baseline computed
      tomography scan.

PMID- 27032317
TI  - Pancreaticoduodenectomy with mesenterico-portal vein resection (with video).

PMID- 27032318
TI  - Pulmonary vascular resistance estimated by Doppler echocardiography predicts
      mortality in patients with interstitial lung disease.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a strong predictor of mortality in
      patients with interstitial lung disease (ILD). However, patients with ILD often
      have poor outcomes even in the absence of PH. Pulmonary vascular resistance (PVR)
      assessed by right heart catheterization is a predictor of mortality in patients
      with ILD. However, the clinical utility of PVR assessed by Doppler
      echocardiography (PVRecho) as a predictor of the outcome in patients with ILD
      remains unclear. The aim of this study was to examine whether PVRecho
      independently predicts mortality in patients with ILD. METHODS: Echocardiographic
      examinations were performed in 133 consecutively enrolled patients with ILD (age,
      67+/-9 years; 53% men). Tricuspid annular plane systolic excursion (TAPSE) was
      measured, and PVRecho was calculated by the following formula:
      PVRecho=[TRV*10/time-velocity integral of right ventricular outflow (RVOT
      VTI)]+0.16. Data for parameters of pulmonary functional tests and for serum
      biomarkers, which were measured within 3 months before or after the
      echocardiographic examinations, were collected. RESULTS: During a mean follow-up
      period of 18+/-7 months, 13 patients died due to respiratory failure (n=10),
      heart failure (n=1), or unknown causes (n=2). In univariate analysis, body mass
      index, idiopathic pulmonary fibrosis, use of an antifibrotic drug (AD), RVOT-VTI,
      PVRecho, percentage of predicted vital capacity (%VC), percentage of predicted
      forced expiratory volume in 1second, and percentage of predicted diffusion
      capacity of the lungs for carbon monoxide (%DLco), but not TAPSE or serum
      biomarkers, were significantly associated with mortality. Cox proportional hazard
      multivariate analysis indicated that %VC [hazard ratio (HR): 0.92, p=0.001], use
      of AD (HR: 4.05, p=0.043), and PVRecho (HR: 3.79, p=0.029) independently predict
      mortality in patients with ILD. Replacement of %VC with %DLco in the multivariate
      analysis did not change the results: %DLco (HR: 0.90, p=0.001), use of AD (HR:
      7.53, p=0.029), and PVRecho (HR: 3.65, p=0.020). CONCLUSIONS: In addition to
      parameters of pulmonary function tests and use of AD, increased PVRecho is an
      independent predictor of mortality in patients with ILD who were evaluated for
      screening of PH by echocardiography.

PMID- 27032319
TI  - Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society
      Scientific Statement.
AB  - This Scientific Statement finds that there is no rationale for routine
      prescribing of unregulated, untested, and potentially harmful custom compounded
      bioidentical hormone therapies. 

PMID- 27032322
TI  - Letter to the Editor: Comment on "Reconciling the Log-Linear and Non-Linear
      Aspects of the TSH-Free T4 Relationship: Intra-Individual Analysis of a Large
      Population" by Rothacker K.M., et al.

PMID- 27032323
TI  - Response to the Letter: Comment on "Reconciling the Log-Linear and Non-Log-Linear
      Nature of the TSH-Free T4 Relationship: Intra-Individual Analysis of a Large
      Population" by Rothacker K.M., et al.

PMID- 27032324
TI  - Letter to the Editor: Vitamin D: A Wonder Drug for the Cure of Type 2 Diabetes?

PMID- 27032325
TI  - Response to the Letter by Muscogiuri et al.

PMID- 27032326
TI  - Letter to the Editor: "Dual-5alpha-Reductase Inhibition Promotes Hepatic Lipid
      Accumulation in Man" by Hazlehurst J.M., Oprescu A.I., Nikolaou N., et al.

PMID- 27032327
TI  - Response to the Letter: "Dual-5alpha-Reductase Inhibition Promotes Hepatic Lipid
      Accumulation in Man".

PMID- 27032328
TI  - Letter to the Editor: Eu-Estrogenemia, Hormone Therapy Cessation, and Early
      Mortality.

PMID- 27032329
TI  - Letter to Editor: Comment on"Incidence and Prevalence of Primary
      Hyperparathyroidism in a Racially Mixed Population" by Yeh M.W., Ituarte P.H.,
      Zhou H.C., Nishimoto S., Liu I.L., Harari A., Haigh P.I., Adams A.L.

PMID- 27032330
TI  - Filtered back-projection reconstruction for attenuation proton CT along most
      likely paths.
AB  - This work investigates the attenuation of a proton beam to reconstruct the map of
      the linear attenuation coefficient of a material which is mainly caused by the
      inelastic interactions of protons with matter. Attenuation proton computed
      tomography (pCT) suffers from a poor spatial resolution due to multiple Coulomb
      scattering (MCS) of protons in matter, similarly to the conventional energy-loss
      pCT. We therefore adapted a recent filtered back-projection algorithm along the
      most likely path (MLP) of protons for energy-loss pCT (Rit et al 2013) to
      attenuation pCT assuming a pCT scanner that can track the position and the
      direction of protons before and after the scanned object. Monte Carlo simulations
      of pCT acquisitions of density and spatial resolution phantoms were performed to
      characterize the new algorithm using Geant4 (via Gate). Attenuation pCT assumes
      an energy-independent inelastic cross-section, and the impact of the energy
      dependence of the inelastic cross-section below 100 MeV showed a capping artifact
      when the residual energy was below 100 MeV behind the object. The statistical
      limitation has been determined analytically and it was found that the noise in
      attenuation pCT images is 411 times and 278 times higher than the noise in energy
      loss pCT images for the same imaging dose at 200 MeV and 300 MeV, respectively.
      Comparison of the spatial resolution of attenuation pCT images with a
      conventional straight-line path binning showed that incorporating the MLP
      estimates during reconstruction improves the spatial resolution of attenuation
      pCT. Moreover, regardless of the significant noise in attenuation pCT images, the
      spatial resolution of attenuation pCT was better than that of conventional energy
      loss pCT in some studied situations thanks to the interplay of MCS and
      attenuation known as the West-Sherwood effect. 

PMID- 27032331
TI  - L-Aspartic and l-glutamic acid ester-based ProTides of anticancer nucleosides:
      Synthesis and antitumoral evaluation.
AB  - A series of novel aryloxyphosphoramidate nucleoside prodrugs based on l-aspartic
      acid and l-glutamic acid as amino acid motif has been synthesized and evaluated
      for antitumoral activity. Depending on the cancer cell line studied and on the
      nature of the parent nucleoside compound (gemcitabine, 5-iodo-2'-deoxy-uridine,
      floxuridine or brivudin), the corresponding ProTides are endowed with an improved
      or decreased cytotoxic activity.

PMID- 27032332
TI  - Development and evaluation of a highly reliable assay for SUMO-specific protease
      inhibitors.
AB  - SUMOylation, as a post-translational modification of proteins, plays essential
      regulatory roles in a variety of pathological conditions. In the dynamic process
      of SUMOylation and deSUMOylation, SENPs (SUMO-specific proteases), in charge of
      deconjugation of SUMO (small ubiquitin-related modifier) from substrate proteins,
      have recently been found to be potential therapeutic targets for cancer
      treatment. A reliable and practical assay is much needed to accelerate the
      discovery of SENPs inhibitors. We established a quantitative assay based on
      readily available SDS-PAGE-Coomassie system using RanGAP-SUMO as the substrate,
      thus avoiding the use of expensive fluorescent dyes or the error-prone
      fluorescent reporter. Its reproducibility and reliability were also evaluated in
      this report. 

PMID- 27032333
TI  - A synthetic 2,3-diarylindole induces cell death via apoptosis and autophagy in
      A549 lung cancer cells.
AB  - A series of 2,3-diarylindoles were synthesized via the Larock heteroannulation,
      and evaluated for their anticancer activity against A549 lung cancer cells. The
      most potent compound, PCNT13 with IC50=5.17 MUM, caused the induction of two
      modes of programmed cell death, apoptosis and autophagy.

PMID- 27032334
TI  - Synthesis and evaluation of anticonvulsant properties of new N-Mannich bases
      derived from 3-(1-phenylethyl)- and 3-benzyl-pyrrolidine-2,5-dione.
AB  - Two series of new derivatives of pyrrolidine-2,5-dione were synthesized and
      evaluated for their anticonvulsant properties. Initial screening for their
      anticonvulsant properties was performed in mice after intraperitoneal
      administration, using the maximal electroshock (MES), subcutaneous
      pentylenetetrazole (scPTZ) and 6-Hz seizure tests. Quantitative pharmacological
      research revealed that the highest level of protection was demonstrated by
      compound N-[{4-methylpiperazin-1-yl}-methyl]-3-(1-phenylethyl)-pyrrolidine-2,5
      dione monohydrochloride (22) which was effective both in the scPTZ test (ED50=39
      mg/kg) and in the 6-Hz test (ED50=36 mg/kg). This molecule showed higher potency
      than reference antiepileptic drugs such as ethosuximide, lacosamide and valproic
      acid. With the aim of explaining the possible mechanism of action of the selected
      molecule, its influence on sodium and calcium channels as well as NMDA and GABAA
      receptors binding properties were evaluated in vitro.

PMID- 27032336
TI  - Optical coherence tomography images simulated with an analytical solution of
      Maxwell's equations for cylinder scattering.
AB  - An algorithm for the simulation of image formation in Fourier domain optical
      coherence tomography (OCT) for an infinitely long cylinder is presented. The
      analytical solution of Maxwell's equations for light scattering by a single
      cylinder is employed for the case of perpendicular incidence to calculate OCT
      images. The A-scans and the time-resolved scattered intensities are compared to
      geometrical optics results calculated with a ray tracing approach. The reflection
      peaks, including the whispering gallery modes, are identified. Additionally, the
      Debye series expansion is employed to identify single peaks in the OCT A-scans.
      Furthermore, a Gaussian beam is implemented in order to simulate lateral scanning
      over the cylinder for two-dimensional B-scans. The fields are integrated over a
      certain angular range to simulate a detection aperture. In addition, the solution
      for light scattering by layered cylinders is employed and the various layers are
      identified in the resulting OCT image. Overall, the simulations in this work show
      that OCT images do not always display the real surface of investigated samples.

PMID- 27032337
TI  - Dynamic measurement of local displacements within curing resin-based dental
      composite using optical coherence elastography.
AB  - This study aimed to determine the feasibility of using optical coherence
      elastography to measure internal displacements during the curing phase of a light
      activated, resin-based composite material. Displacement vectors were spatially
      mapped over time within a commercial dental composite. Measurements revealed that
      the orientation of cure-induced displacement vectors varied spatially in a
      complex manner; however, each vector showed a systematic evolution with time.
      Precision of individual displacements was estimated to be ~1 ~1 to 2  MUm 2  MUm
      , enabling submicrometer time-varying displacements to be detected.

PMID- 27032335
TI  - Molecular characterization of a family 5 glycoside hydrolase suggests an induced
      fit enzymatic mechanism.
AB  - Glycoside hydrolases (GHs) play fundamental roles in the decomposition of
      lignocellulosic biomaterials. Here, we report the full-length structure of a
      cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4
      that is entirely dependent on its two ancillary modules (Ig-like module and
      CBM46) for catalytic activity. Using X-ray crystallography, small-angle X-ray
      scattering and molecular dynamics simulations, we propose that the C-terminal
      CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully
      functional active site via a combination of large-scale multidomain
      conformational selection and induced-fit mechanisms. The Ig-like module is
      pivoting the packing and unpacking motions of CBM46 relative to CD in the
      assembly of the binding subsite. This is the first example of a multidomain GH
      relying on large amplitude motions of the CBM46 for assembly of the catalytically
      competent form of the enzyme. 

PMID- 27032339
TI  - Virulence gene profiles in Staphylococcus aureus isolated from cows with
      subclinical mastitis in eastern Poland.
AB  - Staphylococcus aureus is arguably the most important pathogen involved in bovine
      mastitis. The aim of this study was to determine the virulence gene profiles of
      124 Staph. aureus isolates from subclinical mastitis in cows in eastern Poland.
      The presence of 30 virulence genes encoding adhesins, proteases and
      superantigenic toxins was investigated by PCR. The 17 different combinations of
      adhesin genes were identified. Occurrence of eno (91.1%) and fib (82.3%) genes
      was found to be common. The frequency of other adhesion genes fnbA, fnbB, ebps
      were 14.5, 50, 25%, respectively, and for cna and bbp were 1.6%. The etA and etD
      genes, encoding exfoliative toxins, were present in genomes of 5.6 and 8.9%
      isolates, respectively. The splA and sspA, encoding serine protease, were
      detected in above 90% isolates. The most frequent enterotoxin genes were sei
      (21%), sem (19.4%), sen (19.4%), seg (18.5%) and seo (13.7%). The tst gene was
      harboured by 2.4% isolates. The 19 combinations of the superantigenic toxin genes
      were obtained and found in 35.5% of isolates. Three of them (seg, sei, sem, sen,
      seo; sec, seg, sei, sem, sen, seo and seg, sei, sem, sen) were the most frequent
      and found in 16.1% of the isolates. The most common virulotype, present in 17.7%
      of the isolates, was fib, eno, fnbB, splA, splE, sspA. The results indicate the
      variation in the presence of virulence genes in Staph. aureus isolates and
      considerable diversity of isolates that are able to cause mastitis in cows. 

PMID- 27032338
TI  - Role of HIF-1 on phosphofructokinase and fructose 1, 6-bisphosphatase expression
      during hypoxia in the white shrimp Litopenaeus vannamei.
AB  - HIF-1 is a transcription factor that controls a widespread range of genes in
      metazoan organisms in response to hypoxia and is composed of alpha and beta
      subunits. In shrimp, phosphofructokinase (PFK) and fructose bisphosphatase (FBP)
      are up-regulated in hypoxia. We hypothesized that HIF-1 is involved in the
      regulation of PFK and FBP genes in shrimp hepatopancreas under hypoxia. Long
      double stranded RNA (dsRNA) intramuscular injection was utilized to silence
      simultaneously both HIF-1 subunits, and then, we measured the relative expression
      of PFK and FBP, as well as their corresponding enzymatic activities in hypoxic
      shrimp hepatopancreas. The results indicated that HIF-1 participates in the up
      regulation of PFK transcripts under short-term hypoxia since the induction caused
      by hypoxia (~1.6 and ~4.2-fold after 3 and 48h, respectively) is significantly
      reduced in the dsRNA animals treated. Moreover, PFK activity was significantly
      ~2.8-fold augmented after 3h in hypoxia alongside to an ~1.9-fold increment in
      lactate. However, when animals were dsRNA treated, both were significantly
      reduced. On the other hand, FBP transcripts were ~5.3-fold up-regulated in long
      term hypoxic conditions (48h). HIF-1 is involved in this process since FBP
      transcripts were not induced by hypoxia when HIF-1 was silenced. Conversely, the
      FBP activity was not affected by hypoxia, which suggests its possible regulation
      at post-translational level. Taken together, these results position HIF-1 as a
      prime transcription factor in coordinating glucose metabolism through the PFK and
      FBP genes among others, in shrimp under low oxygen environments.

PMID- 27032340
TI  - Size distribution of aerosol particles produced during mining and processing
      uranium ore.
AB  - The aerosol particle size distributions of uranium and its daughter products were
      studied and determined in the area of the Rozna mine, which is the last active
      uranium mine in the Czech Republic. A total of 13 samples were collected using
      cascade impactors from three sites that had the highest expected levels of dust,
      namely, the forefield, the end of the ore chute and an area close to workers at
      the crushing plant. The characteristics of most size distributions were very
      similar; they were moderately bimodal, with a boundary approximately 0.5 MUm
      between the modes. The activity median aerodynamic diameter (AMAD) and geometric
      standard deviation (GSD) were obtained from the distributions beyond 0.39 MUm,
      whereas the sizes of particles below 0.39 MUm were not differentiated. Most AMAD
      and GSD values in the samples ranged between 3.5 and 10.5 MUm and between 2.8 and
      5.0, respectively. The geometric means of the AMADs and GSDs from all of the
      underground sampling sites were 4.2 MUm and 4.4, respectively, and the geometric
      means of the AMADs and GSDs for the crushing plant samplings were 9.8 MUm and
      3.3, respectively. The weighted arithmetic mean of the AMADs was 4.9 MUm, with a
      standard error of 0.7 MUm, according to the numbers of workers at the workplaces.
      The activity proportion of the radon progeny to (226)Ra in the aerosol was 0.61. 

PMID- 27032341
TI  - Influence of water management and fertilizer application on (137)Cs and (133)Cs
      uptake in paddy rice fields.
AB  - Cesium-137 derived from the Tokyo Electric Power Company's Fukushima Dai-ichi
      Nuclear Power Plant (FDNPP) accident contaminated large areas of agricultural
      land in Eastern Japan. Previous studies before the accident have indicated that
      flooding enhances radiocesium uptake in rice fields. We investigated the
      influence of water management in combination with fertilizers on (137)Cs
      concentrations in rice plants at two fields in southern Ibaraki Prefecture.
      Stable Cs ((133)Cs) in the plants was also determined as an analogue for
      predicting (137)Cs behavior after long-term aging of soil (137)Cs. The
      experimental periods comprised 3 y starting from 2012 in one field, and 2 y from
      2013 in another field. These fields were divided into three water management
      sections: a long-flooding section without midsummer drainage, and medial
      flooding, and short-flooding sections with one- or two-week midsummer drainage
      and earlier end of flooding than the long-flooding section. Six or four types of
      fertilizer subsections (most differing only in potassium application) were nested
      in each water management section. Generally, the long-flooding treatment led to
      higher (137)Cs and (133)Cs concentrations in both straw and brown rice than
      medial- and short-flooding treatments, although there were some notable
      exceptions in the first experimental year at each site. Effects of differing
      potassium fertilizer treatments were cumulative; the effects on (137)Cs and
      (133)Cs concentrations in rice plants were not obvious in 2012 and 2013, but in
      2014, these concentrations were highest where potassium fertilizer had been
      absent and lowest where basal dressings of K had been tripled. The relationship
      between (137)Cs and (133)Cs in rice plants was not correlative in the first
      experimental year at each site, but correlation became evident in the subsequent
      year(s). This study demonstrates a novel finding that omitting midsummer drainage
      and/or delaying drainage during the grain-filling period enhances uptake of both
      (137)Cs and (133)Cs. 

PMID- 27032342
TI  - Fukushima Daiichi Nuclear Plant accident: Atmospheric and oceanic impacts over
      the five years.
AB  - The Fukushima Daiichi Nuclear Plant (FDNPP) accident resulted in huge
      environmental and socioeconomic impacts to Japan. To document the actual
      environmental and socioeconomic effects of the FDNPP accident, we describe here
      atmospheric and marine contamination due to radionuclides released from the FDNPP
      accident using papers published during past five years, in which temporal and
      spatial variations of FDNPP-derived radionuclides in air, deposition and seawater
      and their mapping are recorded by local, regional and global monitoring
      activities. High radioactivity-contaminated area in land were formed by the
      dispersion of the radioactive cloud and precipitation, depending on land
      topography and local meteorological conditions, whereas extremely high
      concentrations of (131)I and radiocesium in seawater occurred due to direct
      release of radioactivity-contaminated stagnant water in addition to atmospheric
      deposition. For both of atmosphere and ocean, numerical model simulations,
      including local, regional and global-scale modeling, were extensively employed to
      evaluate source terms of the FDNPP-derived radionuclides from the monitoring
      data. These models also provided predictions of the dispersion and high
      deposition areas of the FDNPP-derived radionuclides. However, there are
      significant differences between the observed and simulated values. Then, the
      monitoring data would give a good opportunity to improve numerical modeling. 

PMID- 27032343
TI  - OOSPORE VARIATION IN CLOSELY RELATED CHARA TAXA(1).
AB  - Charophytes produce a thick-walled zygote, the so-called oospore, the characters
      of which (size, shape, and structure) are used as taxonomic determination
      criteria. In the present study, the variation of length, width, length-to-width
      ratio, and number of striae of oospores collected both from the field and after
      cross-fertilization experiments was compared within and among taxa, populations,
      and individuals belonging to the Chara baltica Bruzelius "species complex."
      Although the oospore characteristics differed significantly among the taxa, the
      variations among populations belonging to the same taxon and even among
      individuals belonging to the same population were still higher. Oospores
      developed by means of allogamy were not significantly different from oospores
      developed by autogamy. Oospores were 5% shorter and 27% narrower when measured
      dry compared with wet material. Information about this treatment is unfortunately
      lacking in charophyte monographs and oospore determination keys. We concluded
      that oospore descriptions of different charophyte taxa should be based on a
      larger amount of data material collected from different populations and
      individuals and accompanied by a detailed method description, and that a
      determination of closely related taxa by means of oospores should be interpreted
      carefully. Ecological aspects of oospore size variation are discussed. 

PMID- 27032344
TI  - MEASUREMENT OF IN SITU SPECIFIC GROWTH RATES OF MICROCYSTIS (CYANOBACTERIA) FROM
      THE FREQUENCY OF DIVIDING CELLS(1).
AB  - Diel changes in the frequency of dividing cells (FDC) of three Microcystis
      species were investigated in a small eutrophic pond from July to October 2005.
      The representative species was M. aeruginosa (Kutz.) Kutz., constituting 57%-86%
      of the Microcystis population throughout the study period, and the remainder were
      M. viridis (A. Braun) Lemmerm. and M. wesenbergii (Komarek) Komarek. The FDC of
      M. aeruginosa and M. wesenbergii increased in the daytime and fell in the
      nighttime in July and August, but this regular variation was not observed in
      September or October. The in situ specific growth rates of Microcystis species
      were estimated based on the assumption that the specific growth rate can be given
      as an absolute value of the derivative of FDC with respect to time. The
      calculated values were similar among species-0.15-0.38 . d(-1) for M. aeruginosa,
      0.14-0.63 . d(-1) for M. viridis, and 0.18-0.61 . d(-1) for M. wesenbergii. The
      specific growth rates in July and August slightly exceeded those in September and
      October. The analysis of the in situ specific growth rate of Microcystis
      indicated that recruitment of the benthic population or morphological change,
      rather than massive growth, was at least partly responsible for the dominance of
      M. aeruginosa in the study pond. 

PMID- 27032345
TI  - NUTRIENT EFFECTS ON SEAGRASS EPIPHYTE COMMUNITY STRUCTURE IN FLORIDA BAY(1).
AB  - A field experiment was employed in Florida Bay investigating the response of
      seagrass epiphyte communities to nitrogen (N) and phosphorus (P) additions. While
      most of the variability in epiphyte community structure was related to
      uncontrolled temporal and spatial environmental heterogeneity, P additions
      increased the relative abundance of the red algae-cyanobacterial complex and
      green algae, with a concomitant decrease in diatoms. When N was added along with
      P, the observed changes to the diatoms and the red algae-cyanobacterial complex
      were in the same direction as P-only treatments, but the responses were decreased
      in magnitude. Within the diatom community, species relative abundances, species
      richness, and diversity responded weakly to nutrient addition. P additions
      produced changes in diatom community structure that were limited to summer and
      were stronger in eastern Florida Bay than in the western bay. These changes were
      consistent with well-established temporal and spatial patterns of P limitation.
      Despite the significant change in community structure resulting from P addition,
      diatom communities from the same site and time, regardless of nutrient treatment,
      remained more similar to one another than to the diatom communities subject to
      identical nutrient treatments from different sites and times. Overall, epiphyte
      communities exhibited responses to P addition that were most evident at the
      division level. 

PMID- 27032346
TI  - VERTICAL MIGRATION OF A MIXED-SPECIES EUGLENA (EUGLENOPHYTA) ASSEMBLAGE
      INHABITING THE HIGH-INTERTIDAL SANDS OF NYE BEACH, OREGON(1).
AB  - Comparatively little is known about the vertical migration of the
      microphytobenthic community forming visible patches on high-energy beaches. We
      collected surface and cored samples to evaluate the timing and extent of downward
      migration of a multispecies Euglena assemblage inhabiting Nye Beach, Oregon.
      Euglena density at the surface was highly variable and was not correlated with
      the time of low tide or instantaneous irradiance measurements; however,
      triplicate cores collected at low and high tides revealed a tidal rhythm in mean
      depth. On average, 95% of the assemblage occurred within 1 cm of the surface
      during low tide, but 54% of the assemblage was collected between 1 and 8 cm below
      the surface during high tide. A midday shading experiment revealed that short
      term changes in irradiance levels altered the Euglena density at the sediment
      surface by inducing vertical migration. This response to short-term fluctuations
      in light may explain the weak correlation between cell density at the surface and
      time of day. The high-intertidal location of these patches prevented the removal
      of nonmigrating cells by daily high tides, which increased the variability in
      surface samples and obscured the tidal migration rhythm detected in the core
      samples. Due in part to the semidiurnal nature of Oregon tides, this study
      provides in situ confirmation of past mesocosm research indicating that sediment
      disturbance during daily submersed periods is an important process in maintaining
      the quasi-tidal rhythm in the appearance and disappearance of Euglena spp. from
      the surface of beaches and intertidal sandflats. 

PMID- 27032347
TI  - SYMBIODINIUM (DINOPHYTA) DIVERSITY AND STABILITY IN AQUARIUM CORALS(1).
AB  - Indo-Pacific reef corals growing for years in closed-system aquaria provide an
      alternate means to investigate host-symbiont specificity and stability. The
      diversity of dinoflagellate endosymbionts (Symbiodinium spp.) from coral
      communities in private and public aquaria was investigated using molecular
      genetic analyses. Of the 29 symbiont types (i.e., species) identified, 90%
      belonged to the most prevalent group of Symbiodinium harbored by Indo-Pacific
      reef corals, Clade C, while the rest belonged to Clade D. Sixty-five percent of
      all types were known from field surveys conducted throughout the Pacific and
      Indian oceans. Because specific coral-dinoflagellate partnerships appear to have
      defined geographic distributions, correspondence of the same symbionts in
      aquarium and field-collected specimens identifies regions where particular
      colonies must have been collected in the wild. Symbiodinium spp. in clade D,
      believed to be "stress-tolerant" and/or "opportunistic," occurred in a limited
      number of individual colonies. The absence of a prevalent, or "weedy," symbiont
      suggests that conditions under which aquarium corals are grown do not favor
      competitive replacements of their native symbiont populations. The finding of
      typical and diverse assemblages of Symbiodinium spp. among aquarium corals living
      many years under variable chemical/physical conditions, artificial and natural
      light, while undergoing fragmentation periodically, indicates that individual
      colonies maintain stable, long-term symbiotic associations. 

PMID- 27032348
TI  - GENETIC POPULATION STRUCTURE OF PSEUDO-NITZSCHIA PUNGENS (BACILLARIOPHYCEAE) FROM
      THE PACIFIC NORTHWEST AND THE NORTH SEA(1).
AB  - Several species of the diatom Pseudo-nitzschia produce the neurotoxin domoic acid
      (DA). Consumption of fish and shellfish that have accumulated this potent
      excitotoxin has resulted in severe illness and even death in humans, marine
      mammals, and seabirds. Pseudo-nitzschia pungens (Grunow ex Cleve) Hasle is a
      cosmopolitan diatom commonly occurring in the waters of the Pacific Northwest
      (PNW) and the eastern North Atlantic, including the North Sea. However, genetic
      and physiological relationships among populations throughout this large
      geographic distribution have not been assessed. Population genetic parameters
      (e.g., Hardy-Weinberg equilibrium, linkage equilibrium, FST ) calculated for P.
      pungens collected from the Juan de Fuca eddy region in the PNW indicated the
      presence of two distinct groups that were more divergent from each other than
      either was from a P. pungens sample from the North Sea. Geographic heterogeneity
      was also detected within each of the two PNW groups. These results suggested that
      the populations of P. pungens recently mixed in the Juan de Fuca eddy region (a
      seasonally retentive feature off the coasts of Washington State, USA, and
      Vancouver Island, Canada) but did not exchange genetic material by sexual
      reproduction. Alternatively, these two groups may be cryptic (morphologically
      identical, but reproductively isolated) species. Identifying cryptic diversity in
      Pseudo-nitzschia is important for bloom prediction and aiding the identification
      of molecular markers that can be used for rapid detection assay development. 

PMID- 27032349
TI  - NO MECHANISTIC DEPENDENCE OF PHOTOSYNTHESIS ON CALCIFICATION IN THE
      COCCOLITHOPHORID EMILIANIA HUXLEYI (HAPTOPHYTA)(1).
AB  - There is still considerable uncertainty about the relationship between
      calcification and photosynthesis. It has been suggested that since calcification
      in coccolithophorids is an intracellular process that releases CO2 , it enhances
      photosynthesis in a manner analogous to a carbon-concentrating mechanism (CCM).
      The ubiquitous, bloom-forming, and numerically abundant coccolithophorid
      Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler was studied in nutrient
      replete, pH and [CO2 ] controlled, continuous cultures (turbidostats) under a
      range of [Ca(2+) ] from 0 to 9 mM. We examined the long-term, fully acclimated
      photosynthesis-light responses and analyzed the crystalline structure of the
      coccoliths using SEM. The E. huxleyi cells completely lost their coccosphere when
      grown in 0 [Ca(2+) ], while thin, undercalcified and brittle coccoliths were
      evident at 1 mM [Ca(2+) ]. Coccoliths showed increasing levels of calcification
      with increasing [Ca(2+) ]. More robust coccoliths were noted, with no discernable
      differences in coccolith morphology when the cells were grown in either 5 or 9 mM
      (ambient seawater) [Ca(2+) ]. In contrast to calcification, photosynthesis was
      not affected by the [Ca(2+) ] in the media. Cells showed no correlation of their
      light-dependent O2 evolution with [Ca(2+) ], and in all [Ca(2+) ]-containing
      turbidostats, there were no significant differences in growth rate. The results
      show unequivocally that as a process, photosynthesis in E. huxleyi is
      mechanistically independent from calcification. 

PMID- 27032350
TI  - INORGANIC CARBON ACQUISITION BY CHRYSOPHYTES(1).
AB  - Twelve species, representing 12 families of the chrysophytes sensu lato, were
      tested for their ability to take up inorganic carbon. Using the pH-drift
      technique, CO2 compensation points generally varied between 1 and 20 MUmol . L(
      1) with a mean concentration of 5 MUmol . L(-1) . Neither pH nor alkalinity
      affected the CO2 compensation point. The concentration of oxygen had a relatively
      minor effect on CO2 -uptake kinetics, and the mean CO2 compensation point
      calculated from the kinetic curves was 3.6 MUmol . L(-1) at 10-15 kPa starting
      oxygen partial pressure and 3.8 MUmol . L(-1) at atmospheric starting oxygen
      partial pressure (21 kPa). Similarly, uptake kinetics were not affected by
      alkalinity, and hence concentration of bicarbonate. Membrane inlet mass
      spectrometry (MIMS) in the presence and absence of acetazolamide suggested that
      external carbonic anhydrase in Dinobryon sertularia Ehrenb. and Synura petersenii
      Korschikov was either very low or absent. Rates of net HCO3 (-) uptake were very
      low (~5% of oxygen evolution) using MIMS and decreased rather than increased with
      increasing HCO3 (-) concentration, suggesting that it was not a real uptake. The
      CO2 compensation points determined by MIMS for CO2 uptake and oxygen evolution
      were similar to those determined in pH-drift and were >1 MUmol . L(-1) . Overall,
      the results suggest that chrysophytes as a group lack a carbon-concentrating
      mechanism (CCM), or an ability to make use of bicarbonate as an alternative
      source of inorganic carbon. The possible evolutionary and ecological consequences
      of this are briefly discussed. 

PMID- 27032351
TI  - DIFFERENT PHYSIOLOGICAL RESPONSES OF FOUR MARINE SYNECHOCOCCUS STRAINS
      (CYANOPHYCEAE) TO NICKEL STARVATION UNDER IRON-REPLETE AND IRON-DEPLETE
      CONDITIONS(1).
AB  - Synechococcus species are important primary producers in coastal and open-ocean
      ecosystems. When nitrate was provided as the sole nitrogen source, nickel
      starvation inhibited the growth of strains WH8102 and WH7803, while it had little
      effect on two euryhaline strains, WH5701 and PCC 7002. Nickel was required for
      the acclimation of Synechococcus WH7803 to low iron and high light. In WH8102 and
      WH7803, nickel starvation decreased the linear electron transport activity,
      slowed down QA reoxidation, but increased the connectivity factor between
      individual photosynthetic units. Under such conditions, the reduction of their
      intersystem electron transport chains was expected to increase, and their cyclic
      electron transport around PSI would be favored. Nickel starvation decreased the
      total superoxide dismutase (SOD) activity of WH8102 and WH7803 by 30% and 15% of
      the control, respectively. The protein-bound (63) Ni of the oceanic strain WH8102
      comigrated with SOD activity on nondenaturing gels and thus provided additional
      evidence for the existence of active NiSOD in Synechococcus WH8102. In WH7803, it
      seems likely that nickel starvation affected other metabolic pathways and thus
      indirectly affected the total SOD activity. 

PMID- 27032352
TI  - STREAM PERIPHYTON PHOTOACCLIMATION RESPONSE IN FIELD CONDITIONS: EFFECT OF
      COMMUNITY DEVELOPMENT AND SEASONAL CHANGES(1).
AB  - The photochemical behavior of intact stream periphyton communities in France was
      evaluated in response to the time course of natural light. Intact biofilms grown
      on glass substrata were collected at three development stages in July and
      November, and structural parameters of the biofilms were investigated (diatom
      density and taxonomy). At each season, physiological parameters based on pigment
      analysis (HPLC) and pulse-amplitude-modulated (PAM) chl fluorescence technique
      were estimated periodically during a day from dawn to zenith. Regardless of the
      community studied, the optimal quantum yield of PSII (Fv /Fm ), the effective
      PSII efficiency (PhiPSII ), the nonphotochemical quenching (NPQ), and the
      relative electron transport rate (rETR) exhibited clear dynamic patterns over the
      morning. Moreover, microalgae responded to the light increase by developing the
      photoprotective xanthophyll cycle. The analysis of P-I parameters and pigment
      profiles suggests that July communities were adapted to higher light environments
      in comparison with November ones, which could be partly explained by a shift in
      the taxonomic composition. Finally, differences between development stages were
      significant only in July. In particular, photoinhibition was less pronounced in
      mature assemblages, indicating that self-shading (in relation to algal biomass)
      could have influenced photosynthesis in older communities. 

PMID- 27032353
TI  - PRIMARY CARBON AND NITROGEN METABOLIC GENE EXPRESSION IN THE DIATOM THALASSIOSIRA
      PSEUDONANA (BACILLARIOPHYCEAE): DIEL PERIODICITY AND EFFECTS OF INORGANIC CARBON
      AND NITROGEN(1).
AB  - Diel periodicity and effects of inorganic carbon (Ci ) and NO3 (-) on the
      expression of 11 key genes for primary carbon and nitrogen metabolism, including
      potential C4 photosynthesis, in the marine diatom Thalassiosira pseudonana Hasle
      et Heimdal were investigated. Target gene transcripts were measured by
      quantitative reverse transcriptase-PCR, and some of the gene-encoded proteins
      were analyzed by Western blotting. The diatom was grown with a 12 h photoperiod
      at two different Ci concentrations maintained by air-equilibration with either
      380 MUL . L(-1) (near-ambient) or 100 MUL . L(-1) (low) CO2 . Transcripts of the
      principal Ci and NO3 (-) assimilatory genes RUBISCO LSU (rbcL) and nitrate
      reductase displayed very strong diel oscillations with peaks at the end of the
      scotophase. Considerable diel periodicities were also exhibited by the beta
      carboxylase genes phosphoenolpyruvate carboxylase (PEPC1 and PEPC2) and
      phosphoenolpyruvate carboxykinase (PEPCK), and the Benson-Calvin cycle gene
      sedoheptulose-bisphosphatase (SBPase), with peaks during mid- to late scotophase.
      In accordance with the transcripts, there were substantial diel periodicities in
      PEPC1, PEPC2, PEPCK, and especially rbcL proteins, although they peaked during
      early to mid-photophase. Inorganic carbon had some transient effects on the beta
      carboxylase transcripts, and glycine decarboxylase P subunit was highly up
      regulated by low Ci concentration, indicating increased capacity for
      photorespiration. Nitrogen-starved cells had reduced amounts of carbon metabolic
      gene transcripts, but the PEPC1, PEPC2, PEPCK, and rbcL transcripts increased
      rapidly when NO3 (-) was replenished. The results suggest that the beta
      carboxylases in T. pseudonana play key anaplerotic roles but show no clear
      support for C4 photosynthesis. 

PMID- 27032354
TI  - TRANSCRIPTOMIC ANALYSIS OF GRACILARIA CHANGII (RHODOPHYTA) IN RESPONSE TO HYPER-
      AND HYPOOSMOTIC STRESSES(1).
AB  - Osmotic stress is one of the most significant natural abiotic stresses that occur
      in the intertidal zones. Seaweeds may physiologically acclimate to changing
      osmolarity by altering their transcriptome. Here, we investigated the
      transcriptomic changes of Gracilaria changii (B. M. Xia et I. A. Abbott) I. A.
      Abbott, J. Zhang et B. M. Xia in response to hyper- and hypoosmotic stresses
      using a cDNA microarray approach. Microarray analysis revealed that 199 and 200
      genes from ~3,300 genes examined were up- and down-regulated by >2-fold in
      seaweed samples treated at 50 parts per thousand (ppt) artificial seawater (ASW)
      compared with those at 30 ppt ASW, respectively. The number of genes that were up
      and down-regulated by >2-fold in seaweed samples treated at 10 ppt ASW compared
      with those at 30 ppt ASW were 154 and 187, respectively. A majority of these
      genes were only differentially expressed under hyper- or hypoosmotic conditions,
      whereas 67 transcripts were affected by both stresses. The findings of this study
      have shed light on the expression profiles of many transcripts during the
      acclimation of G. changii to hyperosmotic and hypoosmotic conditions. This
      information may assist in the prioritization of genes to be examined in future
      studies. 

PMID- 27032355
TI  - CELL CYCLE AND CELL MORTALITY OF ALEXANDRIUM MINUTUM (DINOPHYCEAE) UNDER SMALL
      SCALE TURBULENCE CONDITIONS(1).
AB  - Decreased net population growth rates and cellular abundances have been observed
      in dinoflagellate species exposed to small-scale turbulence. Here, we
      investigated whether these effects were caused by alterations in the cell cycle
      and/or by cell mortality and, in turn, whether these two mechanisms depended on
      the duration of exposure to turbulence. The study was conducted on the toxic
      dinoflagellate Alexandrium minutum Halim, with the same experimental design and
      setup used in previous studies to allow direct comparison among results. A
      combination of microscopy and Coulter Counter measurements allowed us to detect
      cell mortality, based on the biovolume of broken cells and thecae. The turbulence
      applied during the exponential growth phase caused an immediate transitory arrest
      in the G2/M phase, but significant mortality did not occur. This finding suggests
      that high intensities of small-scale turbulence can alter the cell division,
      likely affecting the correct chromosome segregation during the dinomitosis. When
      shaking persisted for >4 d, mortality signals and presence of anomalously swollen
      cells appeared, hinting at the activation of mechanisms that induce programmed
      cell death. Our study suggests that the sensitivity of dinoflagellates to
      turbulence may drive these organisms to find the most favorable (calm) conditions
      to complete their division cycle. 

PMID- 27032356
TI  - NOVEL PROTEINS COMPRISING THE STRAMENOPILE TRIPARTITE MASTIGONEME IN OCHROMONAS
      DANICA (CHRYSOPHYCEAE)(1).
AB  - Two-dimensional (2-D) protein analysis of the mastigoneme fraction of the
      chromophyte alga Ochromonas danica E. G. Pringsh. showed the presence of several
      component proteins of the tubular mastigoneme. Adding to the reported gene Ocm1,
      three new genes (Ocm2, Ocm3, and Ocm4) belonging to the Ocm gene family were
      isolated using degenerate primers designed from predicted Ocm1 amino acid
      sequences. The predicted polypeptides encoded by Ocm2, Ocm3, and Ocm4 were
      smaller in size than Ocm1. However, they shared four highly conserved, cysteine
      rich, epithelial growth factor (EGF)-like motifs, potentially involved in protein
      protein interaction. In addition, Ocm2, Ocm3, and Ocm4 showed homology to the SIG
      protein family in the centric diatom Thalassiosira weissflogii (Grunow) Fryxell
      et Hasle, which is up-regulated during early stages of sexual reproduction.
      Immunofluorescence analysis with a polyclonal antibody against the partial amino
      acid sequences of Ocm2, Ocm3, and Ocm4 showed that Ocm2 and Ocm3 were located in
      the basal segment region of mastigonemes attached on the surface of the anterior
      flagellum, and that Ocm4 was located within the tubular shaft portion similar to
      Ocm1. 

PMID- 27032357
TI  - INHIBITION OF CASPASE-LIKE ACTIVITIES PREVENTS THE APPEARANCE OF REACTIVE OXYGEN
      SPECIES AND DARK-INDUCED APOPTOSIS IN THE UNICELLULAR CHLOROPHYTE DUNALIELLA
      TERTIOLECTA(1).
AB  - When the chlorophyte alga Dunaliella tertiolecta Butcher is placed in darkness, a
      form of programmed cell death with many similarities to apoptosis is induced,
      including the induction of caspase-like proteases. Many uncertainties about the
      regulation and mediators that participate in the process remain. To examine the
      relationship between caspase-like activities and different apoptotic events
      (i.e., phosphatidylserine [PS] translocation), increases in membrane permeability
      and numbers of dead cells revealed by SYTOX-green staining, and the generation of
      reactive oxygen species (ROS), we used the broad-range caspase inhibitor Boc-D
      FMK to block the activity of the whole class of caspase-like proteins
      simultaneously. In the presence of the inhibitor, ROS were not produced, and
      cells did not die. Loss of membrane asymmetry, indicated by external labeling of
      PS by annexin V, was apparent at midstages of light deprivation, although it did
      not conform to the typical pattern for PS exposure observed in metazoans or
      vascular plants, which occurs at early stages of the apoptotic event. Thus, we
      have evidence for a link between ROS and cell death involving caspase-like
      enzymes in an alga. The fact that caspase-like inhibitors prevent not only cell
      death, but also ROS and loss of cell membrane integrity and asymmetry, suggests
      that caspase-like proteases might have regulatory roles early in cell death, in
      addition to dismantling functions. 

PMID- 27032358
TI  - ELLIPTOCHLORIS MARINA SP. NOV. (TREBOUXIOPHYCEAE, CHLOROPHYTA), SYMBIOTIC GREEN
      ALGA OF THE TEMPERATE PACIFIC SEA ANEMONES ANTHOPLEURA XANTHOGRAMMICA AND A.
      ELEGANTISSIMA (ANTHOZOA, CNIDARIA)(1).
AB  - Symbiotic green algae from two species of intertidal Pacific sea anemones,
      Anthopleura elegantissima and Anthopleura xanthogrammica, were collected from the
      northeastern Pacific coast of North America across the known range of the
      symbiont. Freshly isolated Anthopleura symbionts were used for both morphological
      and molecular analyses because Anthopleura symbiont cultures were not available.
      Light and transmission electron microscopy supported previous morphological
      studies, showing the symbionts consist of spherical unicells from 5 to 10 MUm in
      diameter, with numerous vesicles, and a single bilobed chloroplast. Pyrenoids
      were not seen in LM, but a thylakoid-free area was observed in TEM, consistent
      with previous findings. Many algal cells extracted from fresh anemone tissue were
      observed in the process of division, producing two autospores within a maternal
      cell wall. The morphology of the green symbionts matches that of Elliptochloris
      Tscherm.-Woess. Molecular phylogenetic analyses of the nuclear SSU rDNA and the
      plastid encoded gene for the large subunit of RUBISCO (rbcL) support the
      monophyly of these green algal symbionts, regardless of host species and
      geographic origin. Phylogenetically, sequences of the Anthopleura symbionts are
      nested within the genus Elliptochloris and are distinct from sequences of all
      other Elliptochloris spp. examined. Given the ecological and phylogenetic
      distinctions among the green algal symbionts in Anthopleura spp. and the named
      species of Elliptochloris, we designate the green algal symbionts as a new
      species, Elliptochloris marina (Trebouxiophyceae, Chlorophyta). 

PMID- 27032359
TI  - MOLECULAR PHYLOGENY OF SELECTED SPECIES OF THE ORDER DINOPHYSIALES (DINOPHYCEAE)
      TESTING THE HYPOTHESIS OF A DINOPHYSIOID RADIATION(1).
AB  - Almost 80 years ago, a radiation scheme based on structural resemblance was first
      outlined for the marine order Dinophysiales. This hypothetical radiation
      illustrated the relationship between the dinophysioid genera and included several
      independent, extant lineages. Subsequent studies have supplied additional
      information on morphology and ecology to these evolutionary lineages. We have for
      the first time combined morphological information with molecular phylogenies to
      test the dinophysioid radiation hypothesis in a modern context. Nuclear-encoded
      LSU rDNA sequences including domains D1-D6 from 27 species belonging to
      Dinophysis Ehrenb., Ornithocercus F. Stein, Phalacroma F. Stein, Amphisolenia F.
      Stein, Citharistes F. Stein, and Histioneis F. Stein were obtained from the
      Indian Ocean. Previously, LSU rDNA has only been determined from one of these. In
      Bayesian analyses, Amphisolenia formed a long basal clade to the other
      dinophysioids. These diverged into two separate lineages, the first comprised
      species with a classical Phalacroma outline, also including the type species P.
      porodictyum F. Stein. Thus, we propose to reinstate the genus Phalacroma. The
      relationship between the genera in the second lineage was not well resolved.
      However, the molecular phylogeny supported monophyly of Histioneis and
      Citharistes and showed the genus Dinophysis to be polyphyletic and in need of a
      taxonomic revision. Species of Ornithocercus grouped with Citharistes, but this
      relationship remained unresolved. The phylogenetic trees furthermore revealed
      convergent evolution of several morphological characters in the dinophysioids.
      According to the molecular data, the dinophysioids appeared to have evolved quite
      differently from the radiation schemes previously hypothesized. Four dinophysioid
      species had identical LSU rDNA sequences to other well-established species. 

PMID- 27032360
TI  - ISOLATION AND CHARACTERIZATION OF CHLORELLA SOROKINIANA GXNN01 (CHLOROPHYTA) WITH
      THE PROPERTIES OF HETEROTROPHIC AND MICROAEROBIC GROWTH(1).
AB  - Heterotrophic and anaerobic microalgae are of significance in both basic research
      and industrial application. A microalga strain was isolated from a wastewater
      treatment pond and identified as Chlorella sorokiniana Shihira et W. R. Krauss
      GXNN01 in terms of morphology, physiology, and phylogeny. The strain grows
      rapidly in heterotrophic or mixotrophic conditions with addition of various
      carbon sources, and even in anaerobic conditions. The maximum growth rate reached
      0.28 d(-1) when using d,l-malate as the carbon source, and the protein content of
      the microalgae was 75.32% in cell dry weight. The strain was shown to be capable
      of (1) utilizing d,l-malate only with light, (2) inhibiting photosynthesis in
      mixotrophic growth, and (3) growing in anaerobic conditions with regular
      photosynthesis and producing oxygen internally. This study demonstrates the
      influence of oxygen (aerobic vs. anaerobic) and metabolic regime (autotrophy,
      mixotrophy, heterotrophy) on the physiological state of the cell. 

PMID- 27032361
TI  - PHYLOGENY OF FOUR DINOPHYSIACEAN GENERA (DINOPHYCEAE, DINOPHYSIALES) BASED ON
      rDNA SEQUENCES FROM SINGLE CELLS AND ENVIRONMENTAL SAMPLES(1).
AB  - Dinoflagellates are a highly diverse and environmentally important group of
      protists with relatively poor resolution of phylogenetic relationships,
      particularly among heterotrophic species. We examined the phylogeny of several
      dinophysiacean dinoflagellates using samples collected from four Atlantic sites.
      As a rule, 3.5 kb of sequence including the nuclear ribosomal genes SSU, 5.8S,
      LSU, plus their internal transcribed spacer (ITS) 1 and 2 regions were determined
      for 26 individuals, including representatives of two genera for which molecular
      data were previously unavailable, Ornithocercus F. Stein and Histioneis F. Stein.
      In addition, a clone library targeting the dinophysiacean ITS2 and LSU sequences
      was constructed from bulk environmental DNA from three sites. Three phylogenetic
      trees were inferred from the data, one using data from this study for cells
      identified to genus or species (3.5 kb, 28 taxa); another containing
      dinoflagellate SSU submissions from GenBank and the 12 new dinophysiacean
      sequences (1.9 kb, 56 taxa) from this study; and the third tree combing data from
      identified taxa, dinophysiacean GenBank submissions, and the clone libraries from
      this study (2.1 kb, 136 taxa). All trees were congruent and indicated a distinct
      division between the genera Phalacroma F. Stein and Dinophysis Ehrenb. The
      cyanobionts containing genera Histioneis and Ornithocercus were also
      monophyletic. This was the largest molecular phylogeny of dinophysoid taxa
      performed to date and was consistent with the view that the genus Phalacroma may
      not be synonymous with Dinophysis. 

PMID- 27032362
TI  - ULTRASTRUCTURE AND LSU rDNA-BASED REVISION OF PERIDINIUM GROUP PALATINUM
      (DINOPHYCEAE) WITH THE DESCRIPTION OF PALATINUS GEN. NOV.(1).
AB  - The name Peridinium palatinum Lauterborn currently designates a freshwater
      peridinioid with 13 epithecal and six cingular plates, and no apical pore
      complex. Freshwater dinoflagellate floras classify it in Peridinium group
      palatinum together with P. pseudolaeve M. Lefevre. General ultrastructure,
      flagellar apparatus, and pusular components of P. palatinum were examined by
      serial section TEM and compared to P. cinctum (O. F. Mull.) Ehrenb. and
      Peridiniopsis borgei Lemmerm., respectively, types of Peridinium and
      Peridiniopsis. Partial LSU rDNA sequences from P. palatinum, P. pseudolaeve and
      several peridinioids, woloszynskioids, gymnodinioids, and other dinoflagellates
      were used for a phylogenetic analysis. General morphology and tabulation of taxa
      in group palatinum were characterized by SEM. Differences in plate numbers,
      affecting both the epitheca and the cingulum, combine with differences in plate
      ornamentation and a suite of internal cell features to suggest a generic-level
      distinction between Peridinium group palatinum and typical Peridinium. The
      branching pattern of the phylogenetic tree is compatible with this conclusion,
      although with low support from bootstrap values and posterior probabilities, as
      are sequence divergences estimated between species in group palatinum, and
      typical Peridinium and Peridiniopsis. Palatinus nov. gen. is proposed with the
      new combinations Palatinus apiculatus nov. comb. (type species; syn. Peridinium
      palatinum), P. apiculatus var. laevis nov. comb., and P. pseudolaevis nov. comb.
      Distinctive characters for Palatinus include a smooth or slightly granulate, but
      not areolate, plate surface, a large central pyrenoid penetrated by cytoplasmic
      channels and radiating into chloroplast lobes, and the presence of a peduncle
      homologous microtubular strand. Palatinus cells exit the theca through the
      antapical-postcingular area. 

PMID- 27032363
TI  - DESCRIPTION OF TYRANNODINIUM GEN. NOV., A FRESHWATER DINOFLAGELLATE CLOSELY
      RELATED TO THE MARINE PFIESTERIA-LIKE SPECIES(1).
AB  - On the basis of morphological (light and electron microscopy) as well molecular
      data, we show that the widely distributed freshwater dinoflagellate presently
      known as Peridiniopsis berolinensis is a member of the family Pfiesteriaceae, an
      otherwise marine and estuarine family of dinoflagellates. P. berolinensis is a
      close relative of the marine species, which it resembles in morphology, mode of
      swimming, food-uptake mechanism, and partial LSU rRNA sequences. It differs from
      all known genera of the family in plate tabulation. P. berolinensis is only
      distantly related to the type species of Peridiniopsis, P. borgei, and is
      therefore transferred to the new genus Tyrannodinium as T. berolinense comb. nov.
      T. berolinense is a very common freshwater flagellate that feeds vigorously on
      other protists and is able to consume injured metazoans much larger than itself.
      Production of toxins has not been reported. 

PMID- 27032364
TI  - ANALYSIS OF A PLASTID MULTIGENE DATA SET AND THE PHYLOGENETIC POSITION OF THE
      MARINE MACROALGA CAULERPA FILIFORMIS (CHLOROPHYTA)(1).
AB  - Molecular phylogenetic relationships within the Chlorophyta have relied heavily
      on rRNA data. These data have revolutionized our insight in green algal
      evolution, yet some class relationships have never been well resolved. A commonly
      used class within the Chlorophyta is the Ulvophyceae, although there is not much
      support for its monophyly. The relationships among the Ulvophyceae,
      Trebouxiophyceae, and Chlorophyceae are also contentious. In recent years,
      chloroplast genome data have shown their utility in resolving relationships
      between the main green algal clades, but such studies have never included marine
      macroalgae. We provide partial chloroplast genome data (~30,000 bp, 23 genes) of
      the ulvophycean macroalga Caulerpa filiformis (Suhr) K. Herig. We show gene order
      conservation for some gene combinations and rearrangements in other regions
      compared to closely related taxa. Our data also revealed a pseudogene (ycf62) in
      Caulerpa species. Our phylogenetic results, based on analyses of a 23-gene
      alignment, suggest that neither Ulvophyceae nor Trebouxiophyceae are
      monophyletic, with Caulerpa being more closely related to the trebouxiophyte
      Chlorella than to Oltmannsiellopsis and Pseudendoclonium. 

PMID- 27032365
TI  - TAXONOMIC REVISION AND GEOGRAPHIC DISTRIBUTION OF THE SUBGENUS SARGASSUM
      (FUCALES, PHAEOPHYCEAE) IN THE WESTERN AND CENTRAL PACIFIC ISLANDS BASED ON
      MORPHOLOGICAL AND MOLECULAR ANALYSES(1).
AB  - The species diversity of the subgenus Sargassum was reassessed for the
      southwestern Pacific with special focus on the Solomon Islands, Vanuatu, Fiji,
      and Wallis. Five taxa were recognized on the basis of morphological characters
      and corroborated by DNA analyses of the nuclear internal transcribed spacer 2
      (ITS-2), chloroplastic partial rbcLS-operon, and mitochondrial cox3. Based on the
      study of diagnoses and type specimens, four taxa were identified to S.
      polyphyllum J. Agardh, S. polycystum C. Agardh, S. aquifolium (Turner) C. Agardh,
      and S. ilicifolium (Turner) C. Agardh, while one taxon remained unidentified. We
      present a key for identification that includes detailed descriptions of the
      species and illustrations of their morphological variability. In light of our
      findings, we propose to consider several new synonymies for S. aquifolium, S.
      ilicifolium, S. polycystum, and S. polyphyllum. We also include a review of
      Sargassum floras from Samoa, Tonga, and Nauru and discuss species distribution in
      the southwest and central Pacific. Finally, DNA phylogenies pointed to the
      polyphyly of section Acanthocarpicae and underlined the need for a new section in
      which to place S. polycystum, S. herporhizum Setch. et N. L. Gardner, and S.
      stolonifolium Phang et T. Yoshida. The new section Polycystae Mattio et Payri is
      described to fit species of the subgenus Sargassum with stolon-like branches. 

PMID- 27032366
TI  - GENETIC MAPPING OF THE LAMINARIA JAPONICA (LAMINARALES, PHAEOPHYTA) USING
      AMPLIFIED FRAGMENT LENGTH POLYMORPHISM MARKERS(1).
AB  - To establish a molecular-marker-assisted system of breeding and genetic study for
      Laminaria japonica Aresch., amplified fragment length polymorphism (AFLP) was
      used to construct a genetic linkage map of L. japonica featuring 230 progeny of
      F2 cross population. Eighteen primer combinations produced 370 polymorphic loci
      and 215 polymorphic loci segregated in a 3:1 Mendelian segregation ratio (P <=
      0.05). Of the 215 segregated loci, 142 were ordered into 27 linkage groups. The
      length of the linkage groups ranged from 6.7 to 90.3 centimorgans (cM) with an
      average length of 49.6 cM, and the total length was 1,085.8 cM, which covered
      68.4% of the estimated 1,586.9 cM genome. The number of mapped markers on each
      linkage group ranged from 2 to 12, averaging 5.3 markers per group. The average
      density of the markers was 1 per 9.4 cM. Based on the marker density and the
      resolution of the map, the constructed linkage map can satisfy the need for
      quantitative trait locus (QTL) location and molecular-marker-assisted breeding
      for Laminaria. 

PMID- 27032367
TI  - Advancements in quantum cascade laser-based infrared microscopy of aqueous media.
AB  - The large mid-infrared absorption coefficient of water frequently hampers the
      rapid, label-free infrared microscopy of biological objects in their natural
      aqueous environment. However, the high spectral power density of quantum cascade
      lasers is shifting this limitation such that mid-infrared absorbance images can
      be acquired in situ within signal-to-noise ratios of up to 100. Even at sample
      thicknesses well above 50 MUm, signal-to-noise ratios above 10 are readily
      achieved. The quantum cascade laser-based microspectroscopy of aqueous media is
      exemplified by imaging an aqueous yeast solution and quantifying glucose
      consumption, ethanol generation as well as the production of carbon dioxide gas
      during fermentation.

PMID- 27032368
TI  - Age- and brain region-dependent alpha-synuclein oligomerization is attributed to
      alterations in intrinsic enzymes regulating alpha-synuclein phosphorylation in
      aging monkey brains.
AB  - We previously reported that the levels of alpha-syn oligomers, which play pivotal
      pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy
      bodies, increase heterogeneously in the aging brain. Here, we show that exogenous
      alpha-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy
      body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms
      higher amounts of phosphorylated and oligomeric alpha-syn than that in extracts
      from younger monkeys and LBP-insusceptible brain regions (cerebellum and
      occipital cortex). The increased alpha-syn phosphorylation and oligomerization in
      the brain extracts from older monkeys and in LBP-susceptible brain regions were
      associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting
      alpha-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A),
      an enzyme inhibiting alpha-syn phosphorylation, in these brain extracts. Further,
      the extent of the age- and brain-dependent increase in alpha-syn phosphorylation
      and oligomerization was reduced by inhibition of PLK2 and activation of PP2A.
      Inversely, phosphorylated alpha-syn oligomers reduced the activity of PP2A and
      showed potent cytotoxicity. In addition, the activity of GCase and the levels of
      ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts
      from older monkeys and in LBP-susceptible brain regions. Our results suggest a
      role for altered intrinsic metabolic enzymes in age- and brain region-dependent
      alpha-syn oligomerization in aging brains. 

PMID- 27032369
TI  - Biodiversity management of organic farming enhances agricultural sustainability.
AB  - Organic farming (OF) has been believed to be capable of curtailing some hazardous
      effects associated with chemical farming (CF). However, debates also exist on
      whether OF can feed a world with increasing human population. We hypothesized
      that some improvements on OF may produce adequate crops and reduce environmental
      pollutions from CF. This paper makes comparative analysis of crop yield, soil
      organic matter and economic benefits within the practice on Biodiversity
      Management of Organic Farming (BMOF) at Hongyi Organic Farm (HOF) over eight
      years and between BMOF and CF. Linking crop production with livestock to maximal
      uses of by-products from each production and avoid xenobiotic chemicals, we have
      achieved beneficial improvement in soil properties, effective pest and weed
      control, and increased crop yields. After eight years experiment, we have
      obtained a gradual but stable increase in crop yields with a 9.6-fold increase of
      net income. The net income of HOF was 258,827 dollars and 24,423 dollars in 2014
      and 2007 respectively. Thus, BMOF can not only feed more population, but also
      increase adaptive capacity of agriculture ecosystems and gain much higher
      economic benefits. 

PMID- 27032370
TI  - Phylogenetic analysis, genetic diversity and relationships between the recently
      segregated species of Corynandra and Cleoserrata from the genus Cleome using DNA
      barcoding and molecular markers.
AB  - Cleome is the largest genus in the family Cleomaceae and it is known for its
      various medicinal properties. Recently, some species from the Cleome genus
      (Cleome viscosa, Cleome chelidonii, Cleome felina and Cleome speciosa) are split
      into genera Corynandra (Corynandra viscosa, Corynandra chelidonii, Corynandra
      felina), and Cleoserrata (Cleoserrata speciosa). The objective of this study was
      to obtain DNA barcodes for these species for their accurate identification and
      determining phylogenetic relationships. Out of 10 screened barcoding regions,
      rbcL, matK and ITS1 regions showed higher PCR efficiency and sequencing success.
      This study added matK, rbcL and ITS1 barcodes for the identification of
      Corynandra chelidonii, Corynandra felina, Cleome simplicifolia and Cleome aspera
      species in existing barcode data. Corynandra chelidonii and Corynandra felina
      species belong to the Corynandra genus, but they are not grouped with the
      Corynandra viscosa species, however clustered with the Cleome species. Molecular
      marker analysis showed 100% polymorphism among the studied plant samples.
      Diversity indices for molecular markers were ranged from He=0.1115-0.1714 and
      I=0.2268-0.2700, which indicates a significant amount of genetic diversity among
      studied species. Discrimination of the Cleome and Corynandra species from
      Cleoserrata speciosa was obtained by two RAPD primers (OPA-4 and RAPD-17) and two
      ISSR primers (ISSR-1 and ISSR-2). RAPD and ISSR markers are useful for the
      genetic characterization of these studied species. The present investigation will
      be helpful to understand the relationships of Cleome lineages with Corynandra and
      Cleoserrata species.

PMID- 27032372
TI  - Coupled molybdenum carbide and reduced graphene oxide electrocatalysts for
      efficient hydrogen evolution.
AB  - Electrochemical water splitting is one of the most economical and sustainable
      methods for large-scale hydrogen production. However, the development of low-cost
      and earth-abundant non-noble-metal catalysts for the hydrogen evolution reaction
      remains a challenge. Here we report a two-dimensional coupled hybrid of
      molybdenum carbide and reduced graphene oxide with a ternary polyoxometalate
      polypyrrole/reduced graphene oxide nanocomposite as a precursor. The hybrid
      exhibits outstanding electrocatalytic activity for the hydrogen evolution
      reaction and excellent stability in acidic media, which is, to the best of our
      knowledge, the best among these reported non-noble-metal catalysts. Theoretical
      calculations on the basis of density functional theory reveal that the active
      sites for hydrogen evolution stem from the pyridinic nitrogens, as well as the
      carbon atoms, in the graphene. In a proof-of-concept trial, an electrocatalyst
      for hydrogen evolution is fabricated, which may open new avenues for the design
      of nanomaterials utilizing POMs/conducting polymer/reduced-graphene oxide
      nanocomposites. 

PMID- 27032371
TI  - Genome-wide generation and use of informative intron-spanning and intron-length
      polymorphism markers for high-throughput genetic analysis in rice.
AB  - We developed genome-wide 84634 ISM (intron-spanning marker) and 16510 InDel
      fragment length polymorphism-based ILP (intron-length polymorphism) markers from
      genes physically mapped on 12 rice chromosomes. These genic markers revealed much
      higher amplification-efficiency (80%) and polymorphic-potential (66%) among rice
      accessions even by a cost-effective agarose gel-based assay. A wider level of
      functional molecular diversity (17-79%) and well-defined precise admixed genetic
      structure was assayed by 3052 genome-wide markers in a structured population of
      indica, japonica, aromatic and wild rice. Six major grain weight QTLs (11.9-21.6%
      phenotypic variation explained) were mapped on five rice chromosomes of a high
      density (inter-marker distance: 0.98 cM) genetic linkage map (IR 64 x Sonasal)
      anchored with 2785 known/candidate gene-derived ISM and ILP markers. The
      designing of multiple ISM and ILP markers (2 to 4 markers/gene) in an individual
      gene will broaden the user-preference to select suitable primer combination for
      efficient assaying of functional allelic variation/diversity and realistic
      estimation of differential gene expression profiles among rice accessions. The
      genomic information generated in our study is made publicly accessible through a
      user-friendly web-resource, "Oryza ISM-ILP marker" database. The known/candidate
      gene-derived ISM and ILP markers can be enormously deployed to identify
      functionally relevant trait-associated molecular tags by optimal-resource
      expenses, leading towards genomics-assisted crop improvement in rice. 

PMID- 27032373
TI  - Expansion of a bitter taste receptor family in a polyphagous insect herbivore.
AB  - The Insect taste system plays a central role in feeding behaviours and co
      evolution of insect-host interactions. Gustatory receptors form the interface
      between the insect taste system and the environment. From genome and
      transcriptome sequencing we identified 197 novel gustatory receptor (GR) genes
      from the polyphagous pest Helicoverpa armigera. These GRs include a significantly
      expanded bitter receptor family (180 GRs) that could be further divided into
      three categories based on polypeptide lengths, gene structure and amino acid
      sequence. Type 1 includes 29 bitter Gr genes that possess introns. Type 2
      includes 13 long intronless bitter Gr genes, while Type 3 comprises 131 short
      intronless bitter Gr genes. Calcium imaging analysis demonstrated that three Type
      3 GRs (HarmGR35, HarmGR50 and HarmGR195) can be activated by a crude extract of
      cotton leaves. HarmGR195, a GR specifically and selectively expressed in adult
      tarsi, showed a specific response to proline, an amino acid widely present in
      plant tissues. We hypothesise that the expansion in the H. armigera GR family may
      be functionally tied to its polyphagous behavior. Understanding the molecular
      basis of polyphagy may provide opportunities for the development of new
      environmentally friendly pest control strategies. 

PMID- 27032375
TI  - Recurrence and risk of progression to lower genital tract malignancy in women
      with high grade VAIN.
AB  - OBJECTIVE: High-grade vaginal intraepithelial neoplasia (VAIN) II-III has a
      variable clinical course. Due to the rarity of VAIN, existing data on the
      efficacy of treatment, risk of recurrence and progression to carcinoma is
      limited. Our objective was to evaluate predictors of recurrent disease and
      describe the risk of progression to carcinoma. METHODS: Under an IRB-approved
      protocol 42 patients with biopsy-proven VAIN II-III from 1995 to 2015 were
      retrospectively identified. Demographics, treatment, and clinical course were
      abstracted from medical records. Patients were followed with semi-annual
      colposcopy and biopsies at physician discretion. Standard statistical analyses
      were applied. RESULTS: Median patient age was 58years old (range 20-81). Median
      follow-up time was 45months (range 9-195). Management included excision (31%),
      laser ablation (33%), topical agents (19%), and observation (10%), with the
      following rates of recurrence: 38%, 43%, 75%, and 50% (p=0.26). 20 patients (48%)
      had recurrent or persistent disease during treatment follow-up. No specific
      primary treatment was significantly more effective in preventing recurrence.
      Recurrence of VAIN II-III occurred at a median of 17.4months (7-78months) from
      time of initial diagnosis. Five (12%) patients developed invasive cancer of the
      lower genital tract. Median time to cancer diagnosis was 64months (30 to
      101months). CONCLUSIONS: Patients with VAIN II-III are at high risk of recurrence
      and progression, suggesting the need for ongoing evaluation with cytology and
      comprehensive colposcopy by a skilled specialist. There were no clear risk
      factors or histopathologic criteria which predicted recurrence or progression to
      cancer.

PMID- 27032374
TI  - A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific
      Kras activation and Pten deletion.
AB  - Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor
      prognosis and its incidence is increasing worldwide. Recently, several types of
      cells have been considered as the origin of ICC, namely cholangiocytes, liver
      progenitor cells, and hepatocytes. Here, we have established a novel mouse model
      of ICC by liver-specific Kras activation and Pten deletion. An activating
      mutation of Kras in combination with deletion of Pten was introduced in embryonic
      hepatic bipotential progenitor cells (so-called hepatoblasts) and mature
      hepatocytes using the Cre-loxP system. As a result, liver-specific Kras
      activation and homozygous Pten deletion cooperated to induce ICCs exclusively. In
      contrast, Kras activation in combination with heterozygous Pten deletion induced
      both ICCs and HCCs, whereas Kras activation alone resulted in HCCs but not ICCs.
      Furthermore, a cell-lineage visualization system using tamoxifen-inducible Cre
      loxP demonstrated that the ICCs did not originate from hepatocytes but from
      cholangiocytes. Our data suggest that mice carrying liver-specific Kras
      activation in combination with homozygous Pten deletion should be useful for the
      investigation of therapeutic strategies for human ICC. 

PMID- 27032376
TI  - The impact of HPV cervical screening on negative large loop excision of the
      transformation zone (LLETZ): A comparative cohort study.
AB  - OBJECTIVE: To determine the incidence and predictors of negative large loop
      excision of the transformation zone (LLETZ) following the introduction of Human
      Papillomavirus (HPV) cervical screening. METHOD: A retrospective cohort study.
      Two independent cohorts, who attended for a LLETZ procedure, before and after the
      introduction of HPV cervical screening were compared. For each cohort, 401
      individuals were randomly selected from a colposcopy database. Clinical and
      colposcopic variables were extracted. The incidence of negative LLETZ was
      estimated in each cohort. Regression analysis was used to adjust for potential
      confounders and explore predictors of negative LLETZ. RESULTS: Eighty women
      (19.9%) from the pre-HPV testing cohort and 54 women (13.4%) from the post-HPV
      cohort were negative for cervical intraepithelial neoplasia (RR 0.75, CI: 0.55 to
      0.93). In the post-HPV testing cohort, independent predictors of negative LLETZ
      were low grade cytology (RR 3.60, CI: 2.18-5.97) and a type 3 transformation zone
      (TZ) (RR 2.88, CI: 1.76-4.72). Women with both low grade cytology and a TZ type 3
      were 10.4 times more likely to have a negative LLETZ (absolute risk 40%, 95% CI:
      27-54%). CONCLUSIONS: Despite a 25% reduction in negative LLETZ following the
      introduction of HPV cervical screening, the incidence is still high. These
      results highlight the importance of continuing to improve the specificity of
      cervical intraepithelial neoplasia screening; this should include the use of
      biomarkers that detect HPV-transforming infections and techniques that sample an
      entirely endocervical transformation zone.

PMID- 27032378
TI  - Serum markers measured in FNA fluids of medullary thyroid carcinoma occurring as
      a cyst.
AB  - BACKGROUND: Diagnosis of medullary thyroid carcinoma (MTC) is still a challenge,
      and the measurement of calcitonin in fine-needle aspiration (FNA) washout has
      been recently introduced. Rarely, MTC presents as a cyst and its preoperative
      detection is difficult. METHODS: A 66-year-old woman was referred to us with high
      serum calcitonin. Ultrasound evaluation showed one cystic and one solid nodule.
      FNA was performed in both nodules and calcitonin, procalcitonin and CEA were
      measured in the aspirate fluids. RESULTS: The markers showed elevated levels in
      the FNA washout of the cyst and the patient was operated on. Final histology
      demonstrated MTC of the cystic nodule. Four weeks later, all serum markers were
      undetectable. CONCLUSIONS: In the presence of a cystic thyroid lesion the
      diagnosis of MTC should be taken into account, and measuring calcitonin in FNA
      fluid is relevant. The determination in FNA of other markers is technically
      feasible but its role should be evaluated in larger series.

PMID- 27032377
TI  - Prescription of extended-duration thromboprophylaxis after high-risk,
      abdominopelvic cancer surgery.
AB  - OBJECTIVE: Extended-duration thromboprophylaxis for 4weeks after discharge has
      been demonstrated to reduce venous thromboembolic events (VTE) in cancer patients
      undergoing abdominopelvic surgery and is recommended in national guidelines. We
      examined the utilization and effectiveness of extended-duration low molecular
      weight heparin prophylaxis in high-risk cancer patients. METHODS: We analyzed
      patients with colon, ovarian, and uterine cancer who underwent surgery from 2009
      to 2013 and who were recorded in the MarketScan database. Multivariable models
      and propensity score analysis with inverse probability of treatment weight were
      developed to examine uptake and predictors of use of post-discharge low molecular
      weight heparin (LMWH), as well as associated adverse events (transfusion, and
      hemorrhage). RESULTS: A total of 63,280 patients were identified. Use of extended
      duration prophylaxis increased from 2009 to 2013 from 1.4% to 1.7% (P=0.67) for
      colectomy, 5.9% to 18.3% for ovarian cancer surgery (P<0.001), and 6.3% to 12.2%
      (P<0.001) for hysterectomy for endometrial cancer. There was no association
      between use of extended-duration prophylaxis and reductions in VTE for any of the
      procedures: colectomy (2.4% with extended-duration prophylaxis vs. 2.9% without
      prophylaxis, OR=0.84; 95% CI, 0.54-1.31), ovarian cancer-directed surgery (3.7%
      vs. 3.6%, OR=1.01; 95% CI, 0.76-1.33), hysterectomy (2.1% vs. 2.1%; OR=0.96; 95%
      CI, 0.67-1.38). Extended-duration prophylaxis was associated with an increased
      risk of adverse postoperative events: 2.20 (95% CI, 1.51-3.19) after colectomy,
      1.24 (95% CI, 0.92-1.68) following ovarian cancer-directed surgery and 0.99 (95%
      CI, 0.66-1.48) for hysterectomy for endometrial cancer. CONCLUSION: Use of
      extended-duration thromboprophylaxis is low among high-risk cancer patients
      undergoing surgery.

PMID- 27032379
TI  - Expression of MMP and TIMP mRNA in peripheral blood leukocytes of patients with
      invasive ductal carcinoma of the breast.
AB  - PURPOSE: An imbalance between matrix metalloproteinases (MMPs) and tissue
      inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis.
      This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1
      and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs)
      and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated
      with clinicopathological characteristics in invasive ductal carcinoma (IDC) of
      the breast. MATERIALS AND METHODS: Blood samples were collected from women newly
      diagnosed with IDC who had not received prior treatment (n = 102). Gene
      expression in PBLs was analyzed by quantitative real-time polymerase chain
      reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA.
      RESULTS: In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were
      significantly higher in premenopausal compared to postmenopausal patients
      (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated
      with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was
      significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1
      expression ratio was higher in human epidermal growth factor receptor 2 (HER2)
      positive patients (p = 0.022). Low-grade tumors had significantly lower
      MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048,
      respectively). TIMP1 plasma concentration was significantly higher in small
      tumors compared with T2-T3 tumors (p = 0.013). CONCLUSIONS: These findings reveal
      an important association between tumor characteristics and expression ratios of
      MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal
      status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the
      MMP2/TIMP3 expression ratio in IDC of the breast.

PMID- 27032380
TI  - Should we maintain deep-moderate neuromuscular block until the end of
      laparoscopic surgery? The evidence and a clash of strong opinions.

PMID- 27032381
TI  - Tumor necrosis factor receptor-associated factor 5 (Traf5) acts as an essential
      negative regulator of hepatic steatosis.
AB  - BACKGROUND & AIMS: Obesity-related metabolic inflammation, insulin resistance
      (IR), and excessive fat accumulation are linked phenomena that promote the
      progression of nonalcoholic fatty liver disease (NAFLD). Previous research has
      indicated that CD40-TRAF5 signaling protects against obesity-related metabolic
      disorders; however, the precise roles and underlying mechanisms of TRAF5 in
      obesity-induced pathological processes have not been fully elucidated. METHODS:
      TRAF5 expression was evaluated in the livers of NAFLD patients, high-fat diet
      (HFD)-induced or genetically (ob/ob) induced obese mice, and in palmitate-treated
      hepatocytes. Gain- or loss-of-function approaches were used to investigate the
      specific roles and mechanisms of hepatic Traf5 under obesity-related pathological
      conditions. RESULTS: TRAF5 expression was decreased in the fatty livers of both
      NAFLD patients and obese mice, and in palmitate-treated hepatocytes in vitro.
      Traf5 overexpression significantly suppressed nonalcoholic steatohepatitis (NASH)
      like phenotypes in mice after HFD treatment for 24weeks and inhibited the
      progression of NAFLD in ob/ob mice. Conversely, Traf5 deficiency resulted in the
      deterioration of metabolic disorders induced by HFD. Investigations of the
      underlying mechanisms revealed that Traf5 regulates hepatic steatosis by
      targeting Jnk signaling. Specifically, Jnk1 rather than Jnk2 is responsible for
      the function of Traf5 in metabolic disorders, as evidenced by the fact that Jnk1
      ablation markedly ameliorates the detrimental effects of Traf5 deficiency on
      obesity, inflammation, IR, hepatic steatosis and fibrosis. CONCLUSIONS: Traf5
      negatively regulates NAFLD/NASH and related metabolic dysfunctions by blocking
      Jnk1 activity, which represents a potential therapeutic target for obesity
      related metabolic disorders. LAY SUMMARY: Lipid accumulation in the liver induces
      degradation of Traf5. Increasing Traf5 ameliorates nonalcoholic fatty liver by
      blocking Jnk1 activity.

PMID- 27032382
TI  - Proximity ligation-induced assembly of DNAzymes for simple and cost-effective
      colourimetric detection of proteins with high sensitivity.
AB  - A novel colourimetric method for protein assays is proposed based on proximity
      ligation induced assembly of Mg(2+)-dependent DNAzymes, which may offer simple,
      cost-effective, sensitive and selective detection of the target protein. 

PMID- 27032383
TI  - PIAS1 binds p300 and behaves as a coactivator or corepressor of the transcription
      factor c-Myb dependent on SUMO-status.
AB  - The PIAS proteins (Protein Inhibitor of Activated STATs) constitute a family of
      multifunctional nuclear proteins operating as SUMO E3 ligases and being involved
      in a multitude of interactions. They participate in a range of biological
      processes, also beyond their well-established role in the immune system and
      cytokine signalling. They act both as transcriptional corepressors and
      coactivators depending on the context. In the present work, we investigated
      mechanisms by which PIAS1 causes activation or repression of c-Myb dependent
      target genes. Analysis of global expression data shows that c-Myb and PIAS1
      knockdowns affect a subset of common targets, but with a dual outcome consistent
      with a role of PIAS1 as either a corepressor or coactivator. Our mechanistic
      studies show that PIAS1 engages in a novel interaction with the acetyltransferase
      and coactivator p300. Interaction and ChIP analysis suggest a bridging function
      where PIAS1 enhances p300 recruitment to c-Myb-bound sites through interaction
      with both proteins. In addition, the E3 activity of PIAS1 enhances further its
      coactivation. Remarkably, the SUMO status of c-Myb had a decisive role,
      indicating a SUMO-dependent switch in the way PIAS1 affects c-Myb, either as a
      coactivator or corepressor. Removal of the two major SUMO-conjugation sites in c
      Myb (2KR mutant), which enhances its activity significantly, turned PIAS1 into a
      corepressor. Also, p300 was less efficiently recruited to chromatin by c-Myb-2KR.
      We propose that PIAS1 acts as a "protein inhibitor of activated c-Myb" in the
      absence of SUMOylation while, in its presence, PIAS behaves as a "protein
      activator of repressed c-Myb". 

PMID- 27032384
TI  - TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) stable silencing increases late
      apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma
      cell line.
AB  - BACKGROUND: TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) modulates apoptotic
      pathways preventing the formation of the apoptosome complex. Our group previous
      study showed that 90% of patients' multiple myeloma (MM) marrow-derived plasma
      cells present TRIAP1 overexpression as compared to normal plasma cells. Due to
      high prevalence and lack of information on TRIAP1's role in MM biology, we
      decided to explore the impact of TRAIP1 through stable gene silencing in MM cell
      lines and its effect on cell cycle and apoptosis. METHODS: TRIAP1 expression was
      examined in MM cell lines by quantitative real time PCR. Cell lines were
      submitted to transduction with lentiviral vector encoding a TRIAP1-specific short
      hairpin RNA (shRNA) and, as control, encoding a non-targeting shRNA (scramble).
      Apoptosis was assessed by flow cytometry with annexin V and propidium iodide
      staining (the later also used for cell cycle), APAF1 and Caspase 9 apoptosome
      related genes expression and Caspase 9 and Caspase 3/7 activity. RESULTS:
      RPMI8226 and U266 cell lines were chosen for transduction experiments since they
      present higher levels of TRIAP1 expression. Inhibition of TRIAP1 in RPMI8226
      cells increased the percentage of apoptotic cells, accompanied by increased
      expression of APAF1 and Caspase 9, and Caspase 9 and Caspase 3/7 activity.
      Transduced U266 cell line did not show sustained inhibition of TRIAP1 expression
      nor apoptosis induction. CONCLUSION: Stable silencing of TRIAP1 induces late
      apoptosis through APAF1/Caspase 9 pathway at least in RPMI8226 cell line,
      suggesting that it could be exploited as a potential target at least for a
      subgroup of MM patients. GENERAL SIGNIFICANCE: In the present study, we
      demonstrated effects of TRIAP1 silencing on RPMI8226 MM cell line and established
      its mechanism mediated through APAF1 and Caspase 9. No relevant effect was found
      after gene silencing in U266 cell line.

PMID- 27032385
TI  - Ultrasensitive Visual Detection of HIV DNA Biomarkers via a Multi-amplification
      Nanoplatform.
AB  - Methodologies to detect disease biomarkers at ultralow concentrations can
      potentially improve the standard of living. A facile and label-free multi
      amplification strategy is proposed for the ultrasensitive visual detection of HIV
      DNA biomarkers in real physiological media. This multi-amplification strategy not
      only exhibits a signficantly low detection limit down to 4.8 pM but also provides
      a label-free, cost-effective and facile technique for visualizing a few molecules
      of nucleic acid analyte with the naked eye. Importantly, the biosensor is capable
      of discriminating single-based mismatch lower than 5.0 nM in human serum samples.
      Moreover, the visual sensing platform exhibits excellent specificity, acceptable
      reusability and a long-term stability. All these advantages could be attributed
      to the nanofibrous sensing platform that 1) has a high surface-area-to-volume
      provided by electrospun nanofibrous membrane, and 2) combines glucose oxidase
      (GOx) biocatalysis, DNAzyme-catalyzed colorimetric reaction and catalytic hairpin
      assembly (CHA) recycling amplification together. This multi-amplification
      nanoplatform promises label-free and visual single-based mismatch DNA monitoring
      with high sensitivity and specificity, suggesting wide applications that range
      from virus detection to genetic disease diagnosis. 

PMID- 27032386
TI  - Adnexal localization of Crohn's disease and recurrent massive ovary cysts.
AB  - In a recent interesting case report, Saborit et al. reported three cases of
      ovarian involvement in Crohn's disease (CD). In the first two cases, there were
      pelvic abscesses due to fistulae of ileal loops affected by CD, with involvement
      of the right ovary, which also showed abscesses and typical granulomas. In the
      third case there was an ovarian abscess, extension of the process by contiguity.
      Granulomatous affectation of the ovaries is rare, with only 18 cases reported in
      the literature to date. Of this, in 17 cases the proposed mechanism of disease
      manifestation is direct fistulization between the small intestine and the ovary,
      which allows passage of vegetable material and results in the formation of
      reactive granulomas. In only one case a patient that did not demonstrate the
      histological features of either fistula-related disease (an intact ovarian
      capsule was found) or idiopathic granulomatous disease caused by the multiplicity
      of the granulomas and the presence of central necrosis has been reported. The
      authors therefore suggested that their findings were consistent with a diagnosis
      of metastatic CD of the ovary. 

PMID- 27032387
TI  - Level of radiation dose in university hospital noninsured private health
      screening programs in Korea.
AB  - OBJECTIVES: The aim of this study is to evaluate radiation exposure resulting
      from the comprehensive health examinations of selected university hospital
      programs and to present basic data for research and management strategies on the
      health effects of medical radiation exposure. METHODS: Radiation-based diagnostic
      studies of the comprehensive health examination programs of ten university
      hospitals in Seoul, Korea, as introduced in their websites, were analyzed. The
      medical radiation studies of the programs were reviewed by radiologists. Only the
      effective doses of the basic studies were included in the analysis. The optional
      studies of the programs were excluded. RESULTS: Among the 190 comprehensive
      health examination programs, 132 programs (69.5%) included computed tomography
      studies, with an average of 1.4 scans. The average effective dose of radiation by
      program was 3.62 mSv for an intensive program for specific diseases; 11.12 mSv
      for an intensive program for cancer; 18.14 mSv for a premium program; and 24.08
      mSv for an overnight program. A higher cost of a programs was linked to a higher
      effective dose (r=0.812). The effective doses of the examination programs for the
      same purposes differed by as much as 2.1 times by hospital. Inclusion of positron
      emission tomography-computed tomography was the most critical factor in
      determining the level of effective dose. CONCLUSIONS: It was found that radiation
      exposure dose from comprehensive health exam programs targeted for an
      asymptomatic, healthy public reached between 3.6 and 24 times the annual dose
      limit for the general public. Relevant management policies at the national level
      should be provided to minimize medical radiation exposure.

PMID- 27032388
TI  - Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory
      Pathways in a Transgenic Mouse Model of Migraine.
AB  - Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of
      migraine with aura caused by mutations in CACNA1A that encodes the alpha1A
      subunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that
      carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an
      increased susceptibility to cortical spreading depression (CSD), the mechanism
      underlying migraine aura. Here, we analysed gene expression profiles from
      isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD
      in order to identify molecular pathways affected by CSD. Gene expression profiles
      were generated using deep serial analysis of gene expression sequencing. Our data
      reveal a signature of inflammatory signalling upon CSD in the cortex of both
      mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice
      specific genes are up-regulated in response to CSD that are implicated in
      interferon-related inflammatory signalling. Our findings show that CSD modulates
      inflammatory processes in both wild-type and mutant brains, but that an
      additional unique inflammatory signature becomes expressed after CSD in a
      relevant mouse model of migraine.

PMID- 27032390
TI  - Pre-hospital Delay after Acute Ischemic Stroke in Central Urban China: Prevalence
      and Risk Factors.
AB  - Timely thrombolytic treatment is paramount after acute ischemic stroke (AIS);
      however, a large proportion of patients experience substantial delays in
      presentation to hospital. This study evaluates the prevalence and risk factors in
      pre-hospital delays after AIS in central urban China. AIS patients from 66
      hospitals in 13 major cities across Hubei Province, between October 1, 2014 and
      January 31, 2015 were interviewed and their medical records were reviewed to
      identify those who suffered pre-hospital delays. Bivariate and multivariate
      analyses were undertaken to determine the prevalence rates and the risk factors
      associated with pre-hospital delays. A total of 1835 patients were included in
      the analysis, with 69.3 % patients reportedly arrived at hospital 3 or more hours
      after onset and 55.3 % patients arrived 6 or more hours after onset. Factors
      associated with increased pre-hospital delays for 3 or more hours were as
      follows: patient had a history of stroke (odds ratio (OR), 1.319, P = 0.028),
      onset location was at home (OR, 1.573, P = 0.002), and patients rather than
      someone else noticed the symptom onset first (OR, 1.711; P < 0.001). In contrast,
      knowing someone who had suffered a stroke, considering any kind of the symptoms
      as severe, transferring from a community-based hospital factors, calling
      emergency number (120), and shorter distance from the onset place to the first
      hospital were independently associated with decreased pre-hospital delays. These
      findings indicate that pre-hospital delays after AIS are common in urban central
      China, and future intervention programs should be focused on public awareness of
      stroke and appropriate response.

PMID- 27032389
TI  - RBD and Neurodegenerative Diseases.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder
      characterized by enacting one's dreams during the REM sleep, with most of the
      dreams being violent or aggressive, so that patients often come to see the doctor
      complaining hurting themselves or bed partners during sleep. Prevalence of RBD,
      based on population, is 0.38-2.01 %, but much higher in patients with
      neurodegenerative diseases, especially synucleinopathies. RBD may herald the
      emergence of synucleinopathies by decades, such that it may be used as an
      effective early marker of neurodegenerative diseases. Pharmaceutical treatment of
      RBD includes clonazepam, melatonin, pramipexole, and some newly reported
      medications. In this review, we summarized the clinical and PSG features of RBD,
      the pathophysiology and the therapy of it, focusing on the correlation between
      neurodegenerative diseases and RBD, in order to emphasize the significance of RBD
      as an early marker of neurodegenerative diseases.

PMID- 27032391
TI  - Activation of Sigma-1 Receptor Alleviates Postpartum Estrogen Withdrawal-Induced
      "Depression" Through Restoring Hippocampal nNOS-NO-CREB Activities in Mice.
AB  - Postpartum depression affects approximately 15 % of mothers; however, its
      pathological mechanisms still remain unclear. Ovariectomized adult mice received
      the administration of estrogen (E2) and progesterone with a subsequent alone E2,
      termed hormone-simulated pregnancy (HSP). Affective behaviors as assessed by
      forced swim and tail suspension tests, hippocampal neuronal nitric oxide synthase
      (nNOS), nitric oxide (NO), cyclic AMP (cAMP) response element binding protein
      (CREB) phosphorylation (phosphor-CREB), and neurosteroidogenesis were examined
      before E2 withdrawal (EW; HSP mice) and on days 2-4 (early-EW mice) and days 8-10
      (late-EW mice) after EW. Depressive-like behaviors were observed in early-EW mice
      but not in late-EW mice. Levels of nNOS, NO, and phosphor-CREB were increased in
      HSP mice followed by a significant decline in early-EW mice with a subsequent
      restoration in late-EW mice. The treatment of early-EW mice with NO donor
      alleviated depressive-like behaviors and decline of phosphor-CREB. The nNOS
      inhibitor and NO scavenger caused depressive-like behaviors and reduced phosphor
      CREB in HSP mice and late-EW mice. Notably, the levels of steroidogenic enzymes
      StAR and P450scc were elevated in late-EW mice. The sigma-1 receptor (sigma1R)
      agonist could alleviate depressive-like behaviors and decline of nNOS-NO-CREB in
      early-EW mice. The pharmacological blockade or deficiency of sigma1R in late-EW
      mice caused depressive-like behaviors with decline of nNOS-NO-CREB. The reduction
      of hippocampal brain-derived neurotrophic factor (BDNF) or N-methyl-D-aspartic
      acid (NMDA) receptor NR2B phosphorylation in early-EW mice could recover in late
      EW mice, which was sensitive to the blockade of sigma1R. The NMDA receptor
      agonist, but not TrkB receptor activator, could correct the decline of nNOS-NO
      CREB in early-EW mice. The findings indicate that the activation of sigma1R can
      alleviate postpartum "depression" through increasing nNOS-NO-CREB activities.

PMID- 27032392
TI  - The Effects of IFN-beta 1a on the Expression of Inflammasomes and Apoptosis
      Associated Speck-Like Proteins in Multiple Sclerosis Patients.
AB  - This study aims to evaluate the effects of treatment with IFN-beta 1alpha on the
      expressions of NLRP3, NLRP1, NLRC4, and AIM2, as inflammasomes, and caspase-1, IL
      1beta, and IL-18, as the downstream molecules of inflammasomes, in a population
      of Iranian multiple sclerosis (MS) patients. In this study, 30 MS patients (22
      women and 8 men) participated. Before receiving any medication and 6A months
      after treatment with standard doses of IFN-beta 1alpha 30A mcg injected
      intramuscularly once a week, blood samples were taken and then the leukocytes
      isolated, total RNAs extracted, and complementary DNAs (cDNAs) synthesized. Gene
      expressions of NLRP3, NLRP1, NLRC4, AIM2, and ASC were evaluated at messenger RNA
      (mRNA) levels using real-time PCR method; for assessing caspase-1 at protein
      level, the Western blot method was used. The amounts of IL-1beta and IL-18 were
      measured in plasma using enzyme-linked immunosorbent assay method. Analysis of
      the results before and after therapy with IFN-beta 1alpha in all patients shows
      significantly decreased expressions of NLRP3, NLRC4, and AIM2. The plasma levels
      of IL-1beta, after treatment with IFN-beta 1alpha, were significantly decreased
      in the MS patients. Based on our results, it appears that NLRP3, NLRC4, and AIM2
      play critical roles in the progression of MS, probably by mediating Th1 and Th17
      responses. It seems that decreased expression of IL-1beta is related to decreased
      production and also functions of inflammasomes.

PMID- 27032394
TI  - A Foot in the Door: Development of a Summer College Student Internship in
      Community Mental Health.

PMID- 27032393
TI  - SCHLAFEN 5 expression correlates with intestinal metaplasia that progresses to
      gastric cancer.
AB  - BACKGROUND: Intestinal metaplasia (IM) is a gastric cancer precursor lesion
      (GCPL) and an extremely high risk factor for progression to gastric cancer (GC).
      Clinical guidelines recommend that patients with extensive IM undergo a
      gastroscopy every 3 years. However, protein biomarkers that indicate a transition
      from IM to GC are lacking. Our group recently identified an interferon-alpha
      (IFNalpha)-responsive gene, Schlafen 4 (Slfn4), in immune cells that correlates
      with metaplastic changes in Helicobacter-infected mice. We therefore tested the
      hypothesis that a human homolog of Slfn4, namely, Schlafen 5 (SLFN5), correlates
      with progression of GCPL to GC. METHODS: Jurkat T-lymphoid and HL-60 myeloid cell
      lines were treated with IFNalpha, and SLFN5 mRNA was quantified by quantitative
      PCR. SLFN5 protein expression in the inflamed gastric mucosa was co-localized to
      specific immune cell types by immunohistochemistry using CD20, CD2, and MAC2
      antibodies. SLFN5 expression was also determined by immunohistochemistry in
      formalin-fixed paraffin-embedded samples from individuals with non-atrophic
      gastritis, atrophic gastritis, complete IM, incomplete IM, and GC, respectively.
      RESULTS: The IFNalpha treatment of Jurkat and HL-60 cells induced SLFN5 mRNA.
      SLFN5 protein was expressed mainly by T lymphocytes in inflamed gastric mucosa.
      The highest level of SLFN5 expression was observed in patients with IM that
      progressed to GC. Receiver operating characteristic curves demonstrated that
      correlating SLFN5 expression with the histologic diagnosis of IM significantly
      increased the probability of identifying patients who may progress to GC.
      CONCLUSION: In this study population, elevated SLFN5 protein expression in
      patients with IM correlated with progression to GC.

PMID- 27032395
TI  - Medical School Factors Associated with Higher Rates of Recruitment into
      Psychiatry.
AB  - OBJECTIVE: The medical school a student attends appears to be a factor in whether
      students eventually match into psychiatry. Knowledge of which factors are
      associated with medical schools with higher recruitment rates into psychiatry may
      assist in developing strategies to increase recruitment. METHODS: Psychiatry
      leaders in medical student education in the 25 highest and lowest recruiting US
      allopathic schools were surveyed concerning various factors that could be
      important such as curriculum, educational leadership, and presence of anti
      psychiatry stigma. The relationship between the survey results of high recruiting
      schools versus those of low recruiting schools was evaluated using Mann-Whitney U
      tests. RESULTS: Factors significantly associated (p < .05) with higher recruiting
      schools included better reputation of the psychiatry department and residents,
      perceived higher respect for psychiatry among non-psychiatry faculty, less
      perception that students dissuaded other students from pursuing psychiatry, and
      longer clerkship length. CONCLUSIONS: Educational culture and climate factors may
      have a significant impact on psychiatry recruitment rates. Clerkship length was
      associated with higher recruiting schools, but several previous studies with more
      complete samples have not shown this.

PMID- 27032396
TI  - Hypoxia-Inducible Factor-1alpha and Autoimmune Lupus, Arthritis.
AB  - Hypoxia elicits an orchestrated response in cells, tissues, and entire organisms
      to survive a hypoxic challenge. On a molecular level, this response can be
      controlled by oxygen-dependent stabilization of the transcription factor hypoxia
      inducible factor (HIF)-1alpha. Recently, studies have shown that HIF-1alpha plays
      an important role in the development and function of T helper (Th) cells,
      regulatory T (Treg) cells, and dendritic cells (DCs). Because these cells are
      critical in the pathogenesis of autoimmune diseases, such as systemic lupus
      erythematosus and rheumatoid arthritis, the roles of HIF-1alpha in these
      autoimmune disorders cannot be neglected. In this review, we discuss recent
      findings on the important roles of HIF-1alpha in immune cells and the possible
      pathologic roles of HIF-1alpha in autoimmune diseases. The obtained information
      may lead to deeper insights into the roles of HIF-1alpha in these disorders. 

PMID- 27032397
TI  - Limitations of anticholinergic cycling in patients with overactive bladder (OAB)
      with urinary incontinence (UI): results from the CONsequences of Treatment
      Refractory Overactive bLadder (CONTROL) study.
AB  - PURPOSE: To describe treatment patterns and outcomes in wet-overactive bladder
      (OAB) patients treated with anticholinergics. METHODS: This study was a
      retrospective claims analysis linked to a one-time patient survey of members of a
      regional medical group located in California. Participants met the following
      criteria: received anticholinergic therapy between January 2008 and May 2012,
      based on pharmacy claims; had a diagnosis of OAB; and reported having >=1 urinary
      incontinence (UI) episode per day at the time of the survey. Outcomes included
      the number of anticholinergics cycled through from treatment initiation until the
      end of follow-up (May 31, 2013); frequency of UI episodes; and patient requests
      for additional help for their OAB symptoms. RESULTS: A total of 620 patients were
      enrolled into the study. During the follow-up period, patients cycled through 1
      to 6 unique anticholinergics; 65 % of the study population used only 1
      anticholinergic, while 35 % used >=2 anticholinergics. Patients reported
      experiencing an average of 3.5 UI episodes per day (3.6, 3.3, and 3.4 episodes
      for 1, 2, and >=3 anticholinergics used, respectively), and over 80 % of patients
      requested additional help for their OAB symptoms, irrespective of how many
      anticholinergics were attempted. CONCLUSION: UI symptom burden and adherence to
      therapy did not change as patients attempted more anticholinergic therapies.
      These results suggest that for patients who remain incontinent after attempting
      an anticholinergic, cycling on additional anticholinergics may not provide any
      additional benefit, resulting in sub-optimal care.

PMID- 27032398
TI  - Supervisor and Organizational Factors Associated with Supervisor Support of Job
      Accommodations for Low Back Injured Workers.
AB  - Purpose Temporary job accommodations contribute to the prevention of chronic work
      disability due to low back pain (LBP) through the facilitation of early return to
      work; yet, workplace dimensions of job accommodation are poorly understood. The
      objective of this study was to determine supervisor and organizational factors
      associated with supervisors' support for temporary job accommodations for LBP
      injured workers. Methods Supervisors were recruited from 19 workplaces in the USA
      and Canada and completed an online survey regarding job accommodation practices
      and potential associated factors with respect to a case vignette of a worker with
      LBP. Multivariable linear regression was used to identify the most parsimonious
      set of factors associated with supervisors' support for accommodations. Results A
      total of 804 supervisors participated with 796 eligible for inclusion in the
      analysis. The final set of factors explained 21 % of the variance in supervisors'
      support for temporary job accommodations. Considerate leadership style (beta =
      0.261; 95 % CI 0.212, 0.310), workplace disability management policies and
      practices (beta = 0.243; 95 % CI 0.188, 0.298), and supervisor autonomy for
      designing and providing workplace accommodations (beta = 0.156; 95 % CI 0.071,
      0.241) had the largest effect on supervisor support for accommodations.
      Conclusion Factors predicting supervisors' likelihood to accommodate LBP injured
      workers include use of considerate leadership style, workplace disability
      management policies and practices, and supervisor autonomy. Workplace
      interventions targeting these factors should be developed and evaluated for their
      ability to improve work disability prevention outcomes.

PMID- 27032399
TI  - Killer-specific secretory (Ksp37) gene expression in subjects with Down's
      syndrome.
AB  - Down syndrome is characterized by dysmorphic features, mental retardation and
      problems of immune deficiency. Chronic infection by Epstein-Barr virus is
      frequently present in subjects with Down syndrome. Ksp37 gene is commonly
      expressed by NK, CD8(+) T, gammadelta T and CD4(+) T cells; these data suggest
      that Ksp37 have cytotoxic properties. An increase of Ksp37 protein serum levels
      it has been showed during the acute phase of Epstein-Barr virus. In this study,
      we evaluated the expression of Ksp37 mRNA, in fibroblasts and leukocytes of DS
      subjects and in normal subjects with realtime reverse transcription-PCR. This
      analysis shows that in fibroblasts and leukocytes of Down syndrome subjects the
      KSP37 gene expression was increased compared with control subjects. The results
      of this study suggest that the expression of Ksp37 gene might be associated with
      increased susceptibility of individuals with Down syndrome to EBV infections and
      autoimmune problems. 

PMID- 27032400
TI  - Assessment of otoacoustic emission suppression in women with migraine and
      phonophobia.
AB  - Given that the medial olivocochlear efferent system reduces the amplitude of
      otoacoustic emissions (OAE), the aim of this study was to establish whether such
      a pathway is affected in women with migraine and phonophobia by means of OAE
      suppression testing. In this prospective case-control study, 55 women (29 with
      migraine and phonophobia and 26 healthy women) were subjected to transient-evoked
      otoacoustic emission (TEOAE) testing at frequencies from 1 to 4 kHz. The
      amplitudes of the TEOAE response before and after exposure to contralateral noise
      and the magnitude of TEOAE suppression were assessed. The average TEOAE
      amplitudes in conditions with and without exposure to contralateral noise were
      not significantly different between the groups. However, the magnitude of TEOAE
      suppression was lower in the group with migraine; that difference was only
      statistically significant for frequencies 1 and 1.5 kHz (p = 0.042 and p = 0.004,
      respectively). In this study, women with migraine and phonophobia exhibited
      deficits in OAE suppression, which points to a disorder affecting the medial
      olivocochlear efferent system. 

PMID- 27032401
TI  - Psychometric properties of the Italian version of the multifactorial memory
      questionnaire for adults and the elderly.
AB  - Reliable and valid metamemory measures are needed to assess subjective memory
      complaints that can be distinct from objective memory performance. The
      Multifactorial Memory Questionnaire (MMQ) evaluates dimensions of subjective
      memory functioning such as frequency of memory problems (Ability), affect related
      to memory abilities (Contentment), and strategy use in everyday life (Strategy).
      To examine the psychometric properties of the Italian version of the MMQ, six
      hundred Italian healthy individuals (aged 25-91 years) completed MMQ, a
      questionnaire assessing metacognition (Cognitive Failures Questionnaire, CFQ) and
      two batteries assessing cognitive global status (Montreal Cognitive Assessment,
      MoCA; Mini Mental State Examination, MMSE). MMQ was easy to administer,
      acceptable, and had good test-retest reliability (r for the total MMQ score
      0.95), and internal consistency (Cronbach's alpha for the total MMQ score =
      0.83). An exploratory factor analysis provided a four-factor solution: "Ability"
      (alpha = 0.99), "Contentment" (alpha = 0.91), "External Strategies" (alpha =
      0.85) and "Internal Strategies" (alpha = 0.78) factors. MMQ total score and MMQ
      Ability factor score showed good convergent validity when compared to CFQ score
      (r rho >= 0.51), whereas MMQ total score and the four MMQ factors showed good
      divergent validity when compared to MoCA and MMSE score (r rho <= 0.27).
      Demographic variables significantly influenced MMQ total score and most subscale
      scores. From the derived linear equations, we computed correction factors for raw
      scores and percentile distribution of adjusted scores. The Italian version of MMQ
      is reliable and valid to assess dimensions of metamemory in adult and elderly
      subjects. 

PMID- 27032402
TI  - A one-to-one telestroke network: the first Italian study of a web-based
      telemedicine system for thrombolysis delivery and patient monitoring.
AB  - Over 10 years after European approval, thrombolysis is still limited by a
      restricted time window and non-optimal territorial coverage. Implementation of
      telestroke can give a growing number of patients access to treatment. We hereby
      present the first Italian telemedicine study applied to both the acute and the
      monitoring phase of stroke care. From January 2011 to December 2013, we tested a
      web-based, drip, and treat interaction model, connecting the cerebrovascular
      specialist of one hub center to the Emergency Department of a Spoke center. We
      then compared thrombolysis delivered using the telestroke model with thrombolysis
      provided at the Hub Stroke Unit at the time when the telemedicine program was
      activated. Telethrombolysis data were then compared with data from the two main
      international telestroke projects (TEMPiS and REACH), and other European
      telestroke studies performed at the time of writing. We collected a total of 131
      thrombolysis procedures (25 telethrombolysis and 106 thrombolysis patients at the
      Stroke Unit). Statistical analysis with the t test yielded no statistically
      significant differences between the two populations in door-to-scan, door-to
      needle (DTN), and onset-to-treatment times (OTT). Our OTT and DTN pathway times
      were longer than the TEMPiS and REACH studies but comparable with other European
      telemedicine trials, despite different models of interaction and number of
      centers. Our study in a northeastern province of Italy confirms the potential of
      applying telemedicine to a cerebrovascular pathology. 

PMID- 27032403
TI  - Description of Pseudomonas gregormendelii sp. nov., a Novel Psychrotrophic
      Bacterium from James Ross Island, Antarctica.
AB  - During the microbiological research performed within the scope of activities of
      Czech expeditions based at the Johann Gregor Mendel Station at James Ross Island,
      Antarctica, two psychrotrophic gram-stain negative non-fluorescent strains CCM
      8506T and CCM 8507 from soil were extensively characterized using genotypic and
      phenotypic methods. Initial characterization using ribotyping with HindIII
      restriction endonuclease and phenotyping implies that both isolates belong to a
      single Pseudomonas species. Sequencing of rrs, rpoB, rpoD and glnA genes of
      strain CCM 8506(T) confirmed affiliation of investigated strains within the genus
      Pseudomonas. Further investigation using automated ribotyping with EcoRI
      (RiboPrinter((r)) Microbial Characterisation System), whole-cell protein
      profiling using the Agilent 2100 Bioanalyzer system, extensive biochemical
      testing and DNA-DNA hybridization experiments confirmed that both investigated
      strains are members of a single taxon which is clearly separated from all
      hitherto described Pseudomonas spp. Based on all findings, we describe a novel
      species Pseudomonas gregormendelii sp. nov. with the type strain CCM 8506(T)
      (=LMG 28632T). 

PMID- 27032404
TI  - The Regulatory Roles of ncRNA Rli60 in Adaptability of Listeria monocytogenes to
      Environmental Stress and Biofilm Formation.
AB  - Listeria monocytogenes is a facultative anaerobic Gram-positive bacterium. It is
      well adapted to external environments and able to infect both humans and animals.
      To understand the impacts of ncRNA Rli60 on the adaptability of L. monocytogenes
      to environmental stresses and biofilm formation, a rli60 deletion strain of L.
      monocytogenes (LM-Deltarli60) was constructed using splicing by overlap extension
      PCR (SOE-PCR) and homologous recombination and then compared it with wild-type
      strain L. monocytogenes EGD-e in the aspects of adaptability to environmental
      stresses by measuring their growth under stresses of different temperatures, and
      acidic, alkaline, hypertonic and alcoholic conditions, and capability of biofilm
      formation by using crystal violet staining, as well as the transcriptional levels
      of genes (gltB and gltC) related to the biofilm formation by real-time
      quantitative PCR (qRT-PCR). The results showed that (1) the growth of LM
      Deltarli60 strain was significantly slower under environmental stresses of low
      temperature (30  degrees C), high temperature (42  degrees C), as well as
      alkaline and alcoholic conditions, (2) the amount of biofilm formed by LM
      Deltarli60 was attenuated, and (3) the transcriptional levels of gltB and gltC
      genes at 24 h and 48 h in LM-Deltarli60 revealed a significant reduction.
      Overall, the results confirmed that ncRNA Rli60 plays important roles in
      regulating the adaptability of L. monocytogenes to environmental stresses and
      biofilm formation possibly through impacting the expression of gltB and gltC
      genes. 

PMID- 27032405
TI  - Medial to posterior release procedure after failure of functional treatment in
      clubfoot: a prospective study.
AB  - PURPOSE: Two conservative techniques for clubfoot treatment are still being
      debated and depend upon the institution's expertise. For >40 years, the current
      institution has been a pioneer in the development of the physiotherapy method;
      however, some severe deformities remain resistant to this method which causes
      pain, sprains, and difficulties wearing shoes. Therefore, a surgical approach was
      developed simultaneously for the treatment of these residual or recurring
      clubfeet. The procedure reproduces the same chronological steps by performing
      forefoot derotation before correcting hindfoot equinus. The aim of the current
      study was to assess the results of this surgical technique. METHODS: All clubfeet
      undergoing surgery between October 1995 and February 2009 were prospectively
      included. Initial severity was based on Dimeglio's classification and final
      outcomes on the International Clubfoot Study Group (ICFSG) outcome evaluation
      system. Last follow-up results were assessed by physical examination and
      radiographs. RESULTS: A total of 137 patients with severe clubfeet (mean Dimeglio
      score 12.0) underwent surgery. At the mean follow-up of 10.8 years, mean ICFSG
      score was 4.3 (range 0-23), and 12 % required revision surgery. The rate of
      undercorrection and overcorrection was low (17 pes-plano-valgus ft and 11 ft with
      undercorrection). Eight feet had a fixed deformity. CONCLUSIONS: Severe
      deformities are more resistant to conservative techniques even for institutions
      with large experience. These deformities require further treatment, including
      surgery if necessary. The medial to posterior soft-tissue release is a valuable
      technique with stable results. LEVEL OF EVIDENCE: Level IV.

PMID- 27032406
TI  - Issues in the Treatment of Neurological Conditions Caused by Reactivation of
      Varicella Zoster Virus (VZV).
AB  - Varicella zoster virus (VZV) is a ubiquitous neurotropic human herpesvirus.
      Primary infection usually causes varicella (chicken pox), after which virus
      becomes latent in ganglia along the entire neuraxis. Decades later, virus
      reactivates to produce herpes zoster (shingles), a painful dermatomally
      distributed vesicular eruption. Zoster may be further complicated by postherpetic
      neuralgia, VZV vasculopathy, myelitis, and segmental motor weakness. VZV
      reactivation has also been associated with giant cell arteritis. This overview
      discusses treatment of various conditions that often require both corticosteroids
      and antiviral drugs. Treatment for VZV-associated disease is often based on case
      reports and small studies rather than large-scale clinical trials. Issues that
      require resolution include the optimal duration of such combined therapy, more
      effective treatment for postherpetic neuralgia, whether some treatments should be
      given orally or intravenously, the widening spectrum of zoster sine herpete, and
      the role of antiviral therapy in giant cell arteritis.

PMID- 27032407
TI  - Polydopamine-coated magnetic nanoparticles for isolation and enrichment of
      estrogenic compounds from surface water samples followed by liquid chromatography
      tandem mass spectrometry determination.
AB  - Estrogens, phytoestrogens, and mycoestrogens may enter into the surface waters
      from different sources, such as effluents of municipal wastewater treatment
      plants, industrial plants, and animal farms and runoff from agricultural areas.
      In this work, a multiresidue analytical method for the determination of 17
      natural estrogenic compounds, including four steroid estrogens, six
      mycoestrogens, and seven phytoestrogens, in river water samples has been
      developed. (Fe3O4)-based magnetic nanoparticles coated by polydopamine
      (Fe3O4@pDA) were used for dispersive solid-phase extraction, and the final
      extract was analyzed by ultra-high performance liquid chromatography coupled with
      tandem mass spectrometry. The Fe3O4 magnetic nanoparticles were prepared by a co
      precipitation procedure, coated by pDA, and characterized by scanning electron
      microscopy, infrared spectroscopy, and elemental analysis. The sample preparation
      method was optimized in terms of extraction recovery, matrix effect, selectivity,
      trueness, precision, method limits of detection, and method limits of
      quantification (MLOQs). For all the 17 analytes, recoveries were >70 % and matrix
      effects were below 30 % when 25 mL of river water sample was treated with 90 mg
      of Fe3O4@pDA nanoparticles. Selectivity was tested by spiking river water samples
      with 50 other compounds (mycotoxins, antibacterials, conjugated hormones, UV
      filters, alkylphenols, etc.), and only aflatoxins and some benzophenones showed
      recoveries >60 %. This method proved to be simple and robust and allowed the
      determination of natural estrogenic compounds belonging to different classes in
      surface waters with MLOQs ranging between 0.003 and 0.1 MUg L(-1). Graphical
      Abstract Determination of natural estrogenic compounds in water by magnetic solid
      phase extraction followed by liquid chromatography-tandem mass spectrometry
      analysis. 

PMID- 27032408
TI  - Development and application of a QuEChERS-based extraction method for the
      analysis of 55 pesticides in the bivalve Scrobicularia plana by GC-MS/MS.
AB  - A method for quantitative determination of 55 pesticides in a bivalve matrix was
      established, based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe)
      extraction and using gas chromatography (GC)-ion trap (IT) mass spectrometry
      (MS/MS). Accomplishing the European SANCO guidelines, this method was validated
      using 5 g of homogenized soft tissue, allowing the quantification of pesticides
      at ng/g of wet weight (ww). Quantification limits and recovery rates ranged from
      0.33 to 10.3 MUg/L and from 78 to 119 %, respectively. As an important mollusc,
      not only from an ecological perspective but also for food consumption, the
      peppery furrow shell (Scrobicularia plana) was sampled at three strategical sites
      (Ria Formosa Lagoon, in the south of Portugal) during 2012-2013, over six
      campaigns. A total of 2160 animals were pooled by place and sex. No statistical
      differences were found among sites or between sexes. Forty percent of the sampled
      pools were above quantification limits, reaching total annual average
      concentrations of ?800 ng/g ww. Additionally, 83 % of the selected compounds
      showed concentrations above the legal limits set by the European Directive
      2013/39/EU. In conclusion, the applied method was successful and proved that
      bivalves were contaminated by the selected pesticides. In future work, this
      methodology can be used to monitor body burdens and obtain data for predicting
      impacts in shellfish consumers. Graphical Abstract Resume of pesticides
      extraction and analyses process from S. plana.

PMID- 27032409
TI  - Label-free C-reactive protein electronic detection with an electrolyte-gated
      organic field-effect transistor-based immunosensor.
AB  - In this contribution, we propose a label-free immunosensor, based on a novel type
      of electrolyte-gated field-effect transistor (EGOFET), for ultrasensitive
      detection of the C-reactive protein (CRP). The recognition layer of the biosensor
      is fabricated by physical adsorption of the anti-CRP monoclonal antibody onto a
      poly-3-hexyl thiophene (P3HT) organic semiconductor surface. A supplementary
      nonionic hydrophilic polymer is used as a blocking agent preventing nonspecific
      interactions and allowing a better orientation of the antibodies immobilized onto
      the P3HT surface. The whole biomolecule immobilization procedure does not require
      any pretreatment of the organic semiconductor surface, and the whole
      functionalization process is completed in less than 30 min. Surface plasmon
      resonance (SPR) measurements were performed to assess the amount of biomolecules
      physisorbed onto the P3HT and to evaluate the CRP binding proprieties of the
      deposited anti-CRP layer. A partial surface coverage of about 23 % of adsorbed
      antibody molecules was found to most efficiently sense the CRP. The electrical
      performance of the EGOFET immunosensor was comparable to that of a bare P3HT
      EGOFET device, and the obtained CRP calibration curve was linear over six orders
      of magnitude (from 4 pM to 2 MUM). The relative standard deviation of the
      individual calibration points, measured on immunosensors fabricated on different
      chips, ranged between 1 and 14 %, and a detection limit of 2 pM (220 ng/L) was
      established. The novel electronic immunosensor is compatible with low-cost
      fabrication procedures and was successfully employed for the detection of the CRP
      biomarker in the clinically relevant matrix serum. Graphical abstract Schematic
      of the EGOFET immunosensor for CRP detection. The anti-CRP monoclonal antibody
      layer is physisorbed on the P3HT organic semiconductor and the CRP is directly
      measured by a label-free electronic EGOFET transducer. 

PMID- 27032410
TI  - A primerless molecular diagnostic: phosphorothioated-terminal hairpin formation
      and self-priming extension (PS-THSP).
AB  - There are various ways that priming can occur in nucleic acid amplification
      reactions. While most reactions rely on a primer to initiate amplification, a
      mechanism for DNA amplification has been developed in which hairpin sequences at
      the 3' terminus of a single-stranded oligonucleotide fold on themselves to
      initiate priming. Unfortunately, this method is less useful for diagnostic
      applications because the self-folding efficiency is low and only works over a
      narrow range of reaction temperatures. In order to adapt this strategy for
      analytical applications we have developed a variant that we term
      phosphorothioated-terminal hairpin formation and self-priming extension (PS
      THSP). In PS-THSP a phosphorothioate (PS) modification is incorporated into the
      DNA backbone, leading to a reduction in the thermal stability of dsDNA and
      increased self-folding of terminal hairpins. By optimizing the number of PS
      linkages that are included in the initial template, we greatly increased self
      folding efficiency and the range of reaction temperatures, ultimately achieving a
      detection limit of 1 pM. This improved method was readily adapted to the
      detection of single nucleotide polymorphisms and to the detection of non-nucleic
      acid analytes, such as alkaline phosphatase, which was quantitatively detected at
      a limit of 0.05 mU/mL, approximately 10-fold better than commercial assays.
      Graphical abstract Efficient self-folding by phosphorothioate (PS) modification.

PMID- 27032412
TI  - The law is not equipped to consider scientific dispute.

PMID- 27032411
TI  - Applying the Policy Ecology Framework to Philadelphia's Behavioral Health
      Transformation Efforts.
AB  - Raghavan et al. (Implement Sci 3(26):1-9, 2008) proposed that effective
      implementation of evidence-based practices requires implementation strategies
      deployed at multiple levels of the "policy ecology," including the
      organizational, regulatory or purchaser agency, political, and social levels.
      However, much of implementation research and practice targets providers without
      accounting for contextual factors that may influence provider behavior. This
      paper examines Philadelphia's efforts to work toward an evidence-based and
      recovery-oriented behavioral health system, and uses the policy ecology framework
      to illustrate how multifaceted, multilevel implementation strategies can
      facilitate the widespread implementation of evidence-based practices. Ongoing
      challenges and implications for research and practice are discussed.

PMID- 27032413
TI  - Zoonotic tuberculosis in occupationally exposed groups in Pakistan.
AB  - BACKGROUND: Bovine tuberculosis (bTB) remains a public health threat in low
      income countries. Data on human tuberculosis (TB) due to Mycobacterium bovis are
      poorly documented in developing countries. AIMS: To determine the occurrence of
      active pulmonary TB due to M. bovis in abattoir workers, butchers, livestock
      farmers and veterinarians and to document their knowledge and practices regarding
      bTB. METHODS: A cross-sectional study of abattoir workers, butchers, livestock
      farmers, veterinary doctors and veterinary assistants, which obtained data on
      socio-demographic conditions, knowledge and practices regarding TB. Sputum
      samples were collected from respondents with a chronic cough. The chi-squared
      test was used for statistical analysis. RESULTS: A total of 141 abattoir workers,
      317 butchers, 50 livestock farmers, five veterinary doctors and three veterinary
      assistants took part. Four out of 16 abattoir workers and 1 out of 50 livestock
      farmers were positive for M. bovis by PCR analysis. Duration of work as an
      abattoir worker was significantly associated (P < 0.05) with prevalence of
      zoonotic TB. The knowledge of abattoir workers, butchers, livestock farmers and
      veterinary assistants regarding transmission of bTB from animals to humans and
      the symptoms of TB in humans was very poor. Most of these workers did not use
      protective equipment and appropriate safe working techniques and were considered
      at high risk of acquiring zoonotic TB. CONCLUSIONS: Zoonotic TB is a significant
      public health issue among professionally exposed groups in Peshawar, Pakistan and
      suggests a need for further detailed investigations of the disease in this and
      similar areas.

PMID- 27032414
TI  - Childhood household dysfunction and risk of self-harm: a cohort study of 107 518
      young adults in Stockholm County.
AB  - BACKGROUND: Childhood household dysfunction (CHD) is a risk indicator for self-
      harm in young adulthood. However, less is known about the effects of cumulative
      exposure to CHD and the role of school performance and childhood psychopathology
      in the relationship. METHODS: We used a Swedish cohort of 107 518 individuals
      born in 1987-91. Register-based CHD indicators included familial death, parental
      substance abuse and psychiatric morbidity, parental somatic disease, parental
      criminality, parental separation/single-parent household, public assistance
      receipt and residential instability. Estimates of risk of self-harm from age 15
      [measured as registered diagnosis of self-harm according to the International
      Classification of Disease (ICD)] were calculated as hazard ratios (HR) with 95%
      confidence intervals (CIs). RESULTS: CHD indicators, with exceptions of familial
      death and parental somatic disease, were associated with an increased risk of
      self-harm. Accumulating CHD indicators increased the risk of self-harm in a
      graded manner, and individuals exposed to five or more indicators had a f5-fold
      risk [hazard ratio (HR): 4.9, 95% CI 3.8-6.4) after adjustment for school
      performance, childhood psychopathology and confounders. Exposure to five or more
      CHD indicators and poor school performance conferred a 20-fold increased risk,
      compared with non-exposed individuals in the highest grade group. The risk was
      elevated by 9-fold for those with five or more CHD indicators and a history of
      childhood psychopathology. CONCLUSION: Childhood household dysfunction is
      associated with the risk of self-harm in young adults, particularly when
      accumulated. The risk is markedly increased in the subgroup of disadvantaged
      children that fail in school or develop childhood psychopathology.

PMID- 27032416
TI  - Surveillance for Heartland Virus (Bunyaviridae: Phlebovirus) in Missouri During
      2013: First Detection of Virus in Adults of Amblyomma americanum (Acari:
      Ixodidae).
AB  - During 2013, we collected and tested ticks for Heartland virus (HRTV), a recently
      described human pathogen in the genus Phlebovirus (Bunyaviridae), from six sites
      in northwestern Missouri. Five sites were properties owned by HRTV patients, and
      the sixth was a conservation area that yielded virus in ticks during 2012. We
      collected 39,096 ticks representing five species; however, two species, Amblyomma
      americanum (L.) (97.6%) and Dermacentor variabilis (Say) (2.3%), accounted for
      nearly all ticks collected. We detected 60 HRTV-positive tick pools and all were
      composed of A americanum: 53 pools of nymphs, six pools of male adults, and one
      pool of female adults. This is the first record of HRTV in adult ticks. Virus was
      detected at five properties that yielded A. americanum ticks, including
      properties owned by four of five patients. Virus was detected at two sites that
      yielded virus in 2012. Detection of virus in multiple years indicates that the
      virus persists in ticks within a relatively small geographic area, although
      infection rates (IR) may vary greatly among sites and between years at a site. IR
      per 1,000 A. americanum in northwestern Missouri during the April-July 2013 study
      period were as follows: all adults, IR = 1.13; adult females, IR = 0.33; adult
      males, IR = 1.90; and nymphs, IR = 1.79. The IR in nymphs, the stage with the
      largest data set, corresponds to 1/559 infected ticks. Having robust estimates of
      IR in various stages for A. americanum should lead to more accurate public health
      messaging and a better understanding of virus transmission.

PMID- 27032417
TI  - Expansion of the Knockdown Resistance Frequency Map for Human Head Lice
      (Phthiraptera: Pediculidae) in the United States Using Quantitative Sequencing.
AB  - Pediculosis is a prevalent parasitic infestation of humans, which is increasing
      due, in part, to the selection of lice resistant to either the pyrethrins or
      pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine
      the extent and magnitude of the kdr-type mutations responsible for this
      resistance, lice were collected from 138 collection sites in 48 U.S. states from
      22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously
      published data were used for comparisons of the changes in the frequency of the
      kdr-type mutations over time. Mean percent resistance allele frequency (mean %
      RAF) values across the three mutation loci were determined from each collection
      site. The overall mean % RAF (+/-SD) for all analyzed lice was 98.3 +/- 10%.
      132/138 sites (95.6%) had a mean % RAF of 100%, five sites (3.7%) had
      intermediate values, and only a single site had no mutations (0.0%). Forty-two
      states (88%) had a mean % RAF of 100%. The frequencies of kdr-type mutations did
      not differ regardless of the human population size that the lice were collected
      from, indicating a uniformly high level of resistant alleles. The loss of
      efficacy of the Nix formulation (Prestige Brand, Tarrytown, NY) from 1998 to 2013
      was correlated to the increase in kdr-type mutations. These data provide a
      plausible reason for the decrease in the effectiveness of permethrin in the Nix
      formulation, which is the parallel increase of kdr-type mutations in lice over
      time.

PMID- 27032418
TI  - Implications of Extracellular Vesicle Transfer on Cellular Heterogeneity in
      Cancer: What Are the Potential Clinical Ramifications?
AB  - The functional and phenotypic heterogeneity of tumor cells represents one of the
      greatest challenges in the successful treatment of cancer patients, because it
      increases the risk that certain individual tumor cells possess the ability to,
      for example, metastasize or to tolerate cytotoxic drugs. This heterogeneity in
      cellular behavior is driven by genetic and epigenetic changes and environmental
      differences. Recent studies suggest that an additional layer of complexity of
      tumor heterogeneity exists, based on the ability of cells to share functional
      biomolecules through local and systemic transfer of extracellular vesicles (EV),
      with profound effects on cellular behavior. The transfer of functional
      biomolecules between various populations of tumor cells and between tumor cells
      and nontumor cells has large consequences for both the tumor cells and the
      microenvironment that support the cellular behavior of tumor cells, and therefore
      for the clinical outcome of cancer. Here, we discuss the latest findings on EV
      transfer and the potential implications of EV-mediated local and systemic
      transmission of phenotypic behavior, particularly in the context of tumor
      heterogeneity, metastatic disease, and treatment response. Cancer Res; 76(8);
      2071-5. (c)2016 AACR.

PMID- 27032420
TI  - Conservation and diversification of polycomb repressive complex 2 (PRC2) proteins
      in the green lineage.
AB  - The polycomb group (PcG) proteins are key epigenetic regulators of gene
      expression in animals and plants. They act in multiprotein complexes, of which
      the best characterized is the polycomb repressive complex 2 (PRC2), which
      catalyses the trimethylation of histone H3 at lysine 27 (H3K27me3) at chromatin
      targets. In Arabidopsis thaliana, PRC2 proteins are involved in the regulation of
      diverse developmental processes, including cell fate determination, vegetative
      growth and development, flowering time control and embryogenesis. Here, we
      systematically analysed the evolutionary conservation and diversification of PRC2
      components in lower and higher plants. We searched for and identified PRC2
      homologues from the sequenced genomes of several green lineage species, from the
      unicellular green alga Ostreococcus lucimarinus to more complicated angiosperms.
      We found that some PRC2 core components, e.g. E(z), ESC/FIE and MSI/p55, are
      ancient and have multiplied coincidently with multicellular evolution. For one
      component, some members are newly formed, especially in the Cruciferae. During
      evolution, higher plants underwent copy number multiplication of various PRC2
      components, which occurred independently for each component, without any obvious
      co-amplification of PRC2 members. Among the amplified members, usually one was
      well-conserved and the others were more diversified. Gene amplification occurred
      at different times for different PcG members during green lineage evolution.
      Certain PRC2 core components or members of them were highly conserved. Our study
      provides an insight into the evolutionary conservation and diversification of PcG
      proteins and may guide future functional characterization of these important
      epigenetic regulators in plants other than Arabidopsis.

PMID- 27032421
TI  - Progress on the role of DNA methylation in aging and longevity.
AB  - Aging is a major risk factor for individuals' health problems. Moreover,
      environmental signals have a widespread influence on the aging process.
      Epigenetic modification, e.g. DNA methylation, represents a link between genetic
      and environmental signals via the regulation of gene transcription. An abundance
      of literature indicates that aberrant epigenetic change occurs throughout the
      aging process at both the cellular and the organismal level. In particular, DNA
      methylation presents globally decreasing and site-specific increasing in aging.
      In this review, we focus on the crucial roles of DNA methylation in aging and age
      related disease and highlight the great potential of DNA methylation as a
      therapeutic target in preventing age-related diseases and promoting healthy
      longevity.

PMID- 27032419
TI  - p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic
      Neoplasia.
AB  - Aberrant regulation of cellular extrusion can promote invasion and metastasis.
      Here, we identify molecular requirements for early cellular invasion using a
      premalignant mouse model of pancreatic cancer with conditional knockout of p120
      catenin (Ctnnd1). Mice with biallelic loss of p120 catenin progressively develop
      high-grade pancreatic intraepithelial neoplasia (PanIN) lesions and neoplasia
      accompanied by prominent acute and chronic inflammatory processes, which is
      mediated, in part, through NF-kappaB signaling. Loss of p120 catenin in the
      context of oncogenic Kras also promotes remarkable apical and basal epithelial
      cell extrusion. Abundant single epithelial cells exit PanIN epithelium basally,
      retain epithelial morphology, survive, and display features of malignancy.
      Similar extrusion defects are observed following p120 catenin knockdown in vitro,
      and these effects are completely abrogated by the activation of S1P/S1pr2
      signaling. In the context of oncogenic Kras, p120 catenin loss significantly
      reduces expression of genes mediating S1P/S1pr2 signaling in vivo and in vitro,
      and this effect is mediated at least, in part, through activation of NF-kappaB.
      These results provide insight into mechanisms controlling early events in the
      metastatic process and suggest that p120 catenin and S1P/S1pr2 signaling enhance
      cancer progression by regulating epithelial cell invasion. Cancer Res; 76(11);
      3351-63. (c)2016 AACR.

PMID- 27032422
TI  - Novel WO3/Sb2S3 Heterojunction Photocatalyst Based on WO3 of Different
      Morphologies for Enhanced Efficiency in Photoelectrochemical Water Splitting.
AB  - We report the fabrication of tungsten trioxide (WO3) with different morphologies
      applied in photoelectrochemical (PEC) water splitting. The antimony sulfide
      (Sb2S3) was incorporated onto WO3 for the first time with the aim of improving
      its photoelectrocatalytic activity under visible-light illumination. In the
      present work, WO3 of different morphologies were fabricated on FTO glass via
      adjusting the pH value via a facile hydrothermal method and the morphological
      effect on the photoelectrocatalytic activity of the obtained samples has been
      discussed. WO3/Sb2S3 heterojunction photoelectrocatalysts were subsequently
      synthesized successfully to further improve the photoelectrocatalytic activity.
      Among them, WO3/Sb2S3 heterojunction photoelectrocatalyst based on WO3 micro
      crystals achieved an enhanced photocurrent of 1.79 mA/cm(2) at 0.8 V versus RHE
      under simulated sunlight, compared to 0.45 mA/cm(2) of pristine WO3 micro
      crystals. This excellent PEC performance benefits from the enhanced light
      absorbance, construction of suitable energy band gap, the improved photogenerated
      electron-hole pairs separation and transfer efficiency, which potentially
      provides new insights into PEC water splitting systems. 

PMID- 27032423
TI  - The value of routine creatine kinase and thyroid stimulating hormone testing in
      patients with suspected fibromyalgia: a cross-sectional study.
AB  - OBJECTIVE: The aim was to examine the prevalence of abnormal creatine kinase (CK)
      and thyroid stimulating hormone (TSH) values and previously unknown myopathy or
      thyroid disease in patients with suspected FM syndrome (FMS). METHODS: All adult
      patients with suspected FMS referred to the study hospital between November 2011
      and April 2014 could participate. Patients with a history of myopathy or a
      previous diagnosis of thyroid disorder were excluded. Outcome measures were the
      percentages of abnormal CK and TSH values and the final diagnosis in those
      patients. RESULTS: Three hundred and seventy-three patients were included in this
      study (94% female, mean age 42 years). Of these patients, 7.5% (95% CI: 5.2,
      10.6%) had an abnormal CK according to the local reference values. Applying the
      European Federation of the Neurological Societies guideline, this changed to 0.5%
      (95% CI: 0.2, 1.9%). In none of these patients was hyperCKaemia-related myopathy
      diagnosed, and the final diagnosis was FMS in 89% of the patients. Of the total
      number of patients, 3.5% (95% CI: 2.1, 5.9%) had an elevated TSH and 1.4% (95 CI:
      0.6, 3.1%) a lowered TSH, with one patient having a somewhat lowered free thyroid
      hormone level. The final diagnosis was FMS in all these patients. CONCLUSION:
      Abnormal CK and TSH values are rare in patients with suspected FMS and do not
      result in an alternative diagnosis. Therefore, it seems that routine testing of
      CK and TSH levels in patients with suspected FMS referred to secondary care does
      not contribute to the diagnostic process.

PMID- 27032426
TI  - Persistent Reliance on Facial Appearance Among Older Adults When Judging
      Someone's Trustworthiness.
AB  - Objectives: When judging someone's trustworthiness, facial appearance is a
      salient but nondiagnostic cue. Such judgments should ideally be based on the
      memory of that person's past behaviors during social interaction. Aging may
      impair memory-based decision making, predicting an age-related decline in
      individuals' adjustment of trustworthiness judgment using such behavioral
      information. However, aging may also facilitate the use of diagnostic information
      for social inference, predicting an age-related improvement. I tested these
      competing predictions to obtain insight into the effects of aging on fraud
      victimization. Method: Thirty-six older adults (OAs) and 36 younger adults (YAs)
      played four rounds of a trust game wherein they were the truster and had to learn
      the distinction between "good" and "bad" trustees who always cooperated with and
      cheated participants, respectively. The trustee's facial appearance (trustworthy-
      and untrustworthy looking) and character (good and bad) were manipulated
      orthogonally. Results: A memory test of the trustees' characters revealed that
      even after four rounds of the game, OAs, but not YAs, were biased to guess that
      trustworthy-looking persons were good trustees. Discussion: Persistent reliance
      on facial trustworthiness could increase one's risk of repeated fraud
      victimization among OAs, because fraudulent people can pretend to look
      trustworthy to acquire another's trust.

PMID- 27032425
TI  - The interaction between physical activity and amount of baseline knee cartilage.
AB  - OBJECTIVES: Conflicting reports of the effect of physical activity on knee
      cartilage may be due to the heterogeneity of populations examined and, in
      particular, the underlying health of the knee joint. This study examined the
      influence of recreational and occupational physical activity on cartilage volume
      loss. METHODS: A total of 250 participants with no significant musculoskeletal
      disease were recruited. A gender-specific median cartilage volume split was used
      to define people in the lowest and highest 50% of baseline cartilage volume.
      Baseline recreational and occupational activity was examined by questionnaire,
      while cartilage volume was assessed by MRI at baseline and 2.4 years later.
      RESULTS: Significant interactions were demonstrable between physical activity and
      cartilage volume loss based on stratification of baseline cartilage volume (all P
      ? 0.03). There was a dose-response relationship between frequently performed
      baseline occupational activities and medial cartilage volume loss in both the low
      (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum,
      95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for
      interaction). Individuals with low baseline cartilage volume who were active in
      their occupation and/or recreational activity had greater medial cartilage volume
      loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P =
      0.02). CONCLUSION: Whereas people with less baseline cartilage volume are more at
      risk of structural knee damage with either heavy occupational or recreational
      workloads or both, individuals with high baseline cartilage volume may
      advantageously modify their risk for knee OA by participating in more frequent
      occupational physical activities.

PMID- 27032424
TI  - Effects of the neutrophil elastase inhibitor EL-17 in rat adjuvant-induced
      arthritis.
AB  - OBJECTIVES: Neutrophil elastase (NE), a granule-associated enzyme, participates
      in connective tissue breakdown and promotes cytokine release and specific
      receptor activation during various inflammatory diseases like RA. NE is increased
      in the SF and cartilage of RA patients and represents a target for the
      development of new therapeutic possibilities. The present research aimed to
      evaluate the preclinical pharmacological profile of the N-benzoylpyrazole
      derivative EL-17, a potent and selective NE inhibitor, in a rat model of RA.
      METHODS: Complete Freund's Adjuvant (CFA) was injected in the tibiotarsal joint
      and the effect of acute or repeated treatments with EL-17 (1-30 mg/kg by mouth)
      were evaluated. RESULTS: On day 14 after CFA injection, a single administration
      of EL-17 significantly reduced CFA-dependent hypersensitivity to mechanical
      noxious stimuli and the postural unbalance related to spontaneous pain. To
      evaluate the preventive efficacy, EL-17 was administered daily starting from the
      day of CFA treatment. Behavioural measurements performed on days 7 and 14 showed
      a progressive efficacy of EL-17 against hypersensitivity to mechanical noxious
      and non-noxious stimuli, as well as a decrease of hind limb weight-bearing
      alterations. Histological evaluation of the tibiotarsal joint (day 14)
      demonstrated significant prevention of articular derangement after EL-17 (30
      mg/kg) treatment. The protective effects of EL-17 directly correlated with a
      complete reversion of the plasma NE activity increase induced by CFA.
      CONCLUSIONS: The NE inhibitor EL-17 relieved articular pain after acute
      administration. Furthermore, repeated treatment reduced the development of
      hypersensitivity and protected joint tissue, revealing a disease-modifying
      profile.

PMID- 27032427
TI  - Adult Age Differences in Eye Movements During Reading: The Evidence From Chinese.
AB  - Objectives: Substantial evidence indicates that older readers of alphabetic
      languages (e.g., English and German) compensate for age-related reading
      difficulty by employing a more risky reading strategy in which words are skipped
      more frequently. The effects of healthy aging on reading behavior for
      nonalphabetic languages, like Chinese, are largely unknown, although this would
      reveal the extent to which age-related changes in reading strategy are universal.
      Accordingly, the present research used measures of eye movements to investigate
      adult age differences in Chinese reading. Method: The eye movements of young (18
      30 years) and older (60+ years) Chinese readers were recorded. Results: The older
      adults exhibited typical patterns of age-related reading difficulty. But rather
      than employing a more risky reading strategy compared with the younger readers,
      the older adults read more carefully by skipping words infrequently, making
      shorter forward eye movements, and fixating closer to the beginnings of two
      character target words in sentences. Discussion: In contrast with the findings
      for alphabetic languages, older Chinese readers appear to compensate for age
      related reading difficulty by employing a more careful reading strategy. Age
      related changes in reading strategy therefore appear to be language specific,
      rather than universal, and may reflect the specific visual and linguistic
      requirements of the writing system.

PMID- 27032428
TI  - Survival Advantage Mechanism: Inflammation as a Mediator of Positive Self
      Perceptions of Aging on Longevity.
AB  - Objective : Previous studies have found that positive self-perceptions of aging
      (SPA) are associated with longer survival; however, a biological mechanism was
      unknown. We examined whether C-reactive protein (CRP), a marker of cumulative
      stress-related inflammation, mediates the relationship between SPA and survival.
      Method : The SPA of participants aged 50 and older in the Health and Retirement
      Study (N = 4,149) were assessed at baseline. Inflammation was measured by the
      level of CRP 4 years later. Survival was followed for up to 6 years. Results : As
      hypothesized, CRP mediated the impact of SPA on survival. Following the steps of
      a mediation analysis, positive SPA at baseline predicted lower CRP after 4 years
      (beta = -.29, p = .03) and longer survival in the 2 years following the CRP
      measurement (beta = .20, p =.003); additionally, lower CRP predicted longer
      survival, after adjusting for positive SPA (beta = -.02, p = .0001). All models
      adjusted for baseline age, CRP, health, sex, race, and education. Discussion : It
      was found that lower CRP partially mediates the relationship between positive SPA
      and longer survival. Hence, this study presents a novel pathway to explain the
      process by which positive SPA extend longevity.

PMID- 27032429
TI  - [Not Available].

PMID- 27032430
TI  - [Not Available].

PMID- 27032431
TI  - [Zika virus epidemic].
AB  - Zika virus is endemic in several parts of the world. February 1, 2016 Zika virus
      was declared a public health emergency by the WHO. This declaration is mainly due
      to a convincing association between Zika virus infection during pregnancy and
      birth defects, like microcephaly, among some of the newborns. Imported cases of
      Zika virus infection to North America, Europe and Denmark have been described.
      The infection in itself is mild and self-limiting. The available diagnostic
      methods are under development, validation and evaluation. In Denmark, some
      promising diagnostics are available at Statens Serum Institut. 

PMID- 27032432
TI  - [Complications in pregnant women with polycystic ovary syndrome].
AB  - Pregnant women with polycystic ovary syndrome (PCOS) are at increased risk of
      pregnancy-related disorders such as gestational diabetes (GDM), gestational
      hypertension and preeclampsia in the 2nd and 3rd trimester. In addition, the risk
      of preterm birth, children who are small and large for gestational age, caesarean
      section and poorer neonatal outcome seem to be elevated, however with less clear
      evidence. Except for the screening for GDM, there is no evidence of a benefit of
      increased surveillance during pregnancy for women with PCOS. 

PMID- 27032433
TI  - [Adrenal insufficiency and treatment with glucocorticosteroid].
AB  - Lately, it has been revealed that cortisol (hydrocortisone) secretion is lower
      than previously thought. Replacement doses of 10-15 mg/24 h seem sufficient in
      non-obese individuals. The day-night variation and in particular the fast
      oscillations in plasma cortisol concentration may be important for the patient's
      well-being. The lack of these fluctuations may explain why quality of life in
      some patients is unsatisfactory despite seemingly adequate substitution. It has
      been assumed that critical disease and stress such as major surgery require
      increased doses of hydrocortisone. Recently, this notion has been questioned, and
      in many patients with serious diseases the amount of hydrocortisone secreted is
      not increased. At present, there is no documentation for the benefit of high
      doses (100-400 mg hydrocortisone) in patients with critical disease and adrenal
      insufficiency. 

PMID- 27032434
TI  - [Perimortem caesarean section and timely decision making].
AB  - Perimortem caesarean section can be decisive for the outcome of a cardiac arrest
      in pregnancy for both mother and fetus. We describe a case story of the
      management of cardiac arrest in early labour where perimortem caesarean section
      proved to be life-saving for both mother and child. The child was delivered alive
      seven minutes after recorded cardiac arrest, and the mother had return of
      spontaneous circulation one minute after delivery. The mother recovered well with
      no serious sequelae to the resuscitation. We discuss the importance of timely
      decision and execution of perimortem caesarean. 

PMID- 27032435
TI  - Therapeutic Potential of Human-Derived Endothelial Colony-Forming Cells in Animal
      Models.
AB  - PURPOSE OF REVIEW: Tissue regeneration requires proper vascularization. In vivo
      studies identified that the endothelial colony-forming cells (ECFCs), a subtype
      of endothelial progenitor cells that can be isolated from umbilical cord or
      peripheral blood, represent a promising cell source for therapeutic
      neovascularization. ECFCs not only are able to initiate and facilitate
      neovascularization in diseased tissue but also can, by acting in a paracrine
      manner, contribute to the creation of favorable conditions for efficient and
      appropriate differentiation of tissue-resident stem or progenitor cells. This
      review outlines the progress in the field of in vivo regenerative and tissue
      engineering studies and surveys why, when, and how ECFCs can be used for tissue
      regeneration. RECENT FINDINGS: Reviewed literature that regard human-derived
      ECFCs in xenogeneic animal models implicates that ECFCs should be considered as
      an endothelial cell source of preference for induction of neovascularization.
      Their neovascularization and regenerative potential is augmented in combination
      with other types of stem or progenitor cells. Biocompatible scaffolds
      prevascularized with ECFCs interconnect faster and better with the host
      vasculature. The physical incorporation of ECFCs in newly formed blood vessels
      grants prolonged release of trophic factors of interest, which also makes ECFCs
      an interesting cell source candidate for gene therapy and delivery of bioactive
      compounds in targeted area. SUMMARY: ECFCs possess all biological features to be
      considered as a cell source of preference for tissue engineering and repair of
      blood supply. Investigation of regenerative potential of ECFCs in autologous
      settings in large animal models before clinical application is the next step to
      clearly outline the most efficient strategy for using ECFCs as treatment.

PMID- 27032436
TI  - 3-methylcytosine in cancer: an underappreciated methyl lesion?

PMID- 27032437
TI  - Validity testing and neuropsychology practice in the VA healthcare system:
      results from recent practitioner survey (.).
AB  - OBJECTIVE: A survey of neuropsychologists in the Veterans Health Administration
      examined symptom/performance validity test (SPVT) practices and estimated base
      rates for patient response bias. METHOD: Invitations were emailed to 387
      psychologists employed within the Veterans Affairs (VA), identified as likely
      practicing neuropsychologists, resulting in 172 respondents (44.4% response
      rate). Practice areas varied, with 72% at least partially practicing in general
      neuropsychology clinics and 43% conducting VA disability exams. RESULTS: Mean
      estimated failure rates were 23.0% for clinical outpatient, 12.9% for inpatient,
      and 39.4% for disability exams. Failure rates were the highest for mTBI and PTSD
      referrals. Failure rates were positively correlated with the number of cases seen
      and frequency and number of SPVT use. Respondents disagreed regarding whether one
      (45%) or two (47%) failures are required to establish patient response bias, with
      those administering more measures employing the more stringent criterion.
      Frequency of the use of specific SPVTs is reported. CONCLUSIONS: Base rate
      estimates for SPVT failure in VA disability exams are comparable to those in
      other medicolegal settings. However, failure in routine clinical exams is much
      higher in the VA than in other settings, possibly reflecting the hybrid nature of
      the VA's role in both healthcare and disability determination. Generally
      speaking, VA neuropsychologists use SPVTs frequently and eschew pejorative terms
      to describe their failure. Practitioners who require only one SPVT failure to
      establish response bias may overclassify patients. Those who use few or no SPVTs
      may fail to identify response bias. Additional clinical and theoretical
      implications are discussed.

PMID- 27032438
TI  - Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide
      based microspheres for nasal drug delivery.
AB  - OBJECTIVE: This work describes the application of natural plant polysaccharide as
      pharmaceutical mucoadhesive excipients in delivery systems to reduce the
      clearance rate through nasal cavity. METHODS: Novel natural polysaccharide
      (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using
      emulsion crosslinking method for the delivery of rizatriptan benzoate (RB)
      through nasal route. Mucoadhesive microspheres were characterized for different
      parameters and nasal clearance of technetium-99m ((99m)Tc)-radiolabeled
      microspheres was determined by using gamma-scintigraphy. RESULTS: Their Fourier
      transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed
      that the drug was stable during preparation of microspheres. Aerodynamic diameter
      of microspheres was in the range 13.23 +/- 1.83-33.57 +/- 3.69 um. Change in drug
      and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency
      and in-vitro release property. Scintigraphs taken at regular interval indicate
      that control solution was cleared rapidly from nasal cavity, whereas microspheres
      showed slower clearance (p < 0.005) with half-life of 160 min. CONCLUSION:
      Natural polysaccharide-based microspheres achieved extended residence by
      minimizing effect of mucociliary clearance with opportunity of sustained delivery
      for longer duration.

PMID- 27032439
TI  - Is obesity linked with episodic memory impairment? A commentary on Cheke, Simons,
      and Clayton (2016).

PMID- 27032440
TI  - Correction to: The role of MRI in the evaluation of secondary progressive
      multiple sclerosis.

PMID- 27032442
TI  - Kafirin Protein Based Electrospun Fibers with Tunable Mechanical Property,
      Wettability, and Release Profile.
AB  - Kafirin (KAF), the prolamine protein from sorghum grain, is a promising resource
      for fabricating renewable and biodegradable materials. However, research efforts
      in fulfilling its potentials are still lacking. In this work, electrospun kafirin
      fibers from acetic acid/dichloromethane solutions are reported for the first
      time. Biodegradable polycaprolactone (PCL) was blended with kafirin to obtain
      hybrid KAF/PCL fiber mats with desirable physical properties. Hydrogen bonding
      between the N-H group of kafirin and the C?O group of PCL was detected in each
      blended formulation. Our small-angle X-ray scattering results indicated that the
      long spacing decreased and the average spacing between crystalline lamellae of
      PCL increased with the increase of kafirin content. Compared to the hydrophobic
      surface of neat PCL fiber mat, KAF/PCL fiber mats under most of the blend ratios
      showed hydrophilic surface character, and the swelling property was composition
      dependent. The fiber mats evolved from brittle ones to flexible ones with the
      increase of relative content of PCL. The most desirable mechanical performance
      was obtained at a kafirin/PCL mass blend ratio of 1:2. To simulate the
      nutraceutical release in body fluid, carnosic acid (CA) was selected as a
      nutraceutical model, and release behaviors in selected KAF/PCL fiber mats were
      found to be diffusion controlled. Whereas the amorphous region of kafirin
      dominated the release rate, PCL functioned as a hydrophobic skeleton to maintain
      the 3D scaffold of the fiber matrix. The fabricated KAF/PCL fiber mats open up
      new applications of underutilized cereal protein in nutraceutical delivery. 

PMID- 27032443
TI  - Silent Brain Infarction in Patients With Asymptomatic Carotid Artery
      Atherosclerotic Disease.
AB  - BACKGROUND AND PURPOSE: The relationship between carotid atherosclerosis and
      ipsilateral silent brain infarction (SBI) is unclear. We tested the hypothesis
      that extracranial internal carotid artery (ICA) stenosis is associated with a
      greater prevalence of SBI in the cerebral hemisphere ipsilateral to ICA disease
      compared with the unaffected, contralateral side. METHODS: We identified patients
      with unilateral extracranial ICA stenosis >=50% on angiography by standard
      imaging criteria. We included patients with recent brain magnetic resonance
      imaging who had no previous history of stroke or transient ischemic attack.
      Blinded readers ascertained the presence of anterior circulation SBIs. SBI was
      defined as either a cavitary lacunar infarction in the white or deep gray matter
      or cortical infarction defined by T2 hyperintense signal in cortical gray matter.
      The Wilcoxon signed-rank test was used to compare SBI in the cerebral hemispheres
      and Cohen kappa to assess inter-rater reliability of SBI evaluation. RESULTS:
      Among 104 patients, we found a higher prevalence of SBIs ipsilateral to ICA
      disease (33%) compared with the contralateral side (20.8%; P=0.0067). There was
      no significant difference in the prevalence of lacunar SBIs (including both white
      and deep gray matter) between hemispheres (P=0.109), but there was a
      significantly higher prevalence of cortical SBIs occurring downstream from ICA
      disease (P=0.0045). High inter-rater reliability was observed (kappa=0.818).
      CONCLUSIONS: Patients with asymptomatic ICA disease demonstrate a higher
      prevalence of SBI downstream from their ICA atherosclerotic disease compared with
      the contralateral side but only of the cortical and not lacunar SBI subtype.

PMID- 27032444
TI  - Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke: A Retrospective
      Pooled Analysis.
AB  - BACKGROUND AND PURPOSE: The debate over the fact that experimental drugs proposed
      for the treatment of stroke fail in the translation to the clinical situation has
      attracted considerable attention in the literature. In this context, we present a
      retrospective pooled analysis of a large data set from preclinical studies, to
      examine the effects of early versus late administration of intravenous
      recombinant tissue-type plasminogen activator. METHODS: We collected data from 26
      individual studies from 9 international centers (13 researchers; 716 animals)
      that compared recombinant tissue-type plasminogen activator with controls, in a
      unique mouse model of thromboembolic stroke induced by an in situ injection of
      thrombin into the middle cerebral artery. Studies were classified into early (<3
      hours) versus late (>=3 hours) drug administration. Final infarct volumes,
      assessed by histology or magnetic resonance imaging, were compared in each study,
      and the absolute differences were pooled in a random-effect meta-analysis. The
      influence of time of administration was tested. RESULTS: When compared with
      saline controls, early recombinant tissue-type plasminogen activator
      administration was associated with a significant benefit (absolute difference, 
      6.63 mm(3); 95% confidence interval, -9.08 to -4.17; I(2)=76%), whereas late
      recombinant tissue-type plasminogen activator treatment showed a deleterious
      effect (+5.06 mm(3); 95% confidence interval, +2.78 to +7.34; I(2)=42%;
      Pint<0.00001). Results remained unchanged after subgroup analyses. CONCLUSIONS:
      Our results provide the basis needed for the design of future preclinical studies
      on recanalization therapies using this model of thromboembolic stroke in mice.
      The power analysis reveals that a multicenter trial would require 123 animals per
      group instead of 40 for a single-center trial.

PMID- 27032446
TI  - Clinical Outcome of Anticoagulant Treatment in Head or Neck Infection-Associated
      Cerebral Venous Thrombosis.
AB  - BACKGROUND AND PURPOSE: Local infections of the head or neck are a cause of
      cerebral venous thrombosis. Treatment of infectious cerebral venous thrombosis
      with heparin is controversial. We examined whether this treatment was associated
      with intracranial hemorrhagic complications and poor clinical outcome. METHODS:
      We retrieved data from a prospective cohort study of 624 cerebral venous
      thrombosis patients. We compared patients with and without an infection of the
      head or neck and anticoagulated versus not anticoagulated. We examined death or
      dependency and new intracerebral hemorrhages. RESULTS: Six hundred four of 624
      patients were eligible for the study. Fifty-seven patients had an infection of
      the head or neck (9.4%). Comparing data between infection and noninfection
      patients, the frequency of therapeutic doses of heparin was similar in both
      groups (82.5% versus 83.7%). New intracerebral hemorrhages were more common in
      patients with an infection (12.3% versus 5.3%; P=0.04), but death or dependency
      did not differ between patients with and without an infection (15.8% versus
      13.7%). In patients with an infection of the head or neck, there was no
      significant difference in the frequency of new intracerebral hemorrhages and poor
      outcome between patients who did or did not receive therapeutic doses of heparin.
      CONCLUSIONS: New intracerebral hemorrhages were more frequent in patients with an
      infection. The use of therapeutic doses of heparin did not seem to influence the
      risk of new intracranial hemorrhages or poor clinical outcome, but the number of
      patients who did not receive anticoagulation was too small to draw firm
      conclusions about safety of heparin in adults with cerebral venous thrombosis and
      an infection of the head or neck.

PMID- 27032445
TI  - Access to Endovascular Treatment in Remote Areas: Analysis of the Reperfusion
      Treatment Registry of Catalonia.
AB  - BACKGROUND AND PURPOSE: Since demonstration of the benefit of endovascular
      treatment (EVT) in acute ischemic stroke patients with proximal arterial
      occlusion, stroke care systems need to be reorganized to deliver EVT in a timely
      and equitable way. We analyzed differences in the access to EVT by geographical
      areas in Catalonia, a territory with a highly decentralized stroke model.
      METHODS: We studied 965 patients treated with EVT from a prospective multicenter
      population-based registry of stroke patients treated with reperfusion therapies
      in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health
      areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily
      covered by local stroke centers located less than hour away from a Comprehensive
      Stroke Center, and (C) areas primarily covered by local stroke centers located
      more than hour away from a Comprehensive Stroke Center. We compared the number of
      EVT*100 000 inhabitants/year and time from stroke onset to groin puncture between
      groups. RESULTS: Baseline characteristics were similar between groups. Throughout
      the study period, there were significant differences in the population rates of
      EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area,
      3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes
      longer in group B (312 minutes [245-435]) and 120 minutes longer in group C (350
      minutes [284-408]) compared with group A (230 minutes [160-407]; P<0.001).
      CONCLUSIONS: Accessibility to EVT from remote areas is hampered by lower rate and
      longer time to treatment compared with areas covered directly by Comprehensive
      Stroke Centers.

PMID- 27032447
TI  - Increasing the sensitivity for stem cell monitoring in system-function based
      magnetic particle imaging.
AB  - The use of superparamagnetic iron oxide nanoparticles (SPIONs) has provided new
      possibilities in biophysics and biomedical imaging technologies. The
      magnetization dynamics of SPIONs, which can be influenced by the environment, are
      of central interest. In this work, different biological SPION environments are
      used to investigate three different calibration methods for stem cell monitoring
      in magnetic particle imaging. It is shown that calibrating using SPIONs
      immobilized via agarose gel or intracellular uptake results in superior stem cell
      image quality compared to mobile SPIONs in saline. This superior image quality
      enables more sensitive localization and identification of a significantly smaller
      number of magnetically labeled stem cells. The results are important for cell
      tracking and monitoring of future SPION based therapies such as hyperthermia
      based cancer therapies, targeted drug delivery, or tissue regeneration approaches
      where it is crucial to image a sufficiently small number of SPIONs interacting
      with biological matter. 

PMID- 27032449
TI  - Effectiveness of a Web-Based Guided Self-help Intervention for Outpatients With a
      Depressive Disorder: Short-term Results From a Randomized Controlled Trial.
AB  - BACKGROUND: Research has convincingly demonstrated that symptoms of depression
      can be reduced through guided Internet-based interventions. However, most of
      those studies recruited people form the general population. There is insufficient
      evidence for the effectiveness when delivered in routine clinical practice in
      outpatient clinics. OBJECTIVE: The objective of this randomized controlled trial
      was to study patients with a depressive disorder (as defined by the Diagnostic
      and Statistical Manual of Disorders, fourth edition), as assessed by trained
      interviewers with the Composite International Diagnostic Interview, who
      registered for treatment at an outpatient mental health clinic. We aimed to
      examine the effectiveness of guided Internet-based self-help before starting face
      to-face treatment. METHODS: We recruited 269 outpatients, aged between 18 and 79
      years, from outpatient clinics and randomly allocated them to Internet-based
      problem solving therapy (n=136), with weekly student support, or to a control
      condition, who remained on the waitlist with a self-help booklet (control group;
      n=133). Participants in both conditions were allowed to take up face-to-face
      treatment at the outpatient clinics afterward. We measured the primary outcome,
      depressive symptoms, by Center for Epidemiological Studies Depression scale (CES
      D). Secondary outcome measures were the Hospital Anxiety and Depression Scale
      Anxiety subscale (HADS-A), Insomnia Severity Index questionnaire (ISI), and
      EuroQol visual analog scale (EQ-5D VAS). All outcomes were assessed by telephone
      at posttest (8 weeks after baseline). RESULTS: Posttest measures were completed
      by 184 (68.4%) participants. We found a moderate to large within-group effect
      size for both the intervention (d=0.75) and the control (d=0.69) group. However,
      the between-group effect size was very small (d=0.07), and regression analysis on
      posttreatment CES-D scores revealed no significant differences between the groups
      (b=1.134, 95% CI -2.495 to 4.763). The per-protocol analysis (>=4 sessions
      completed) results were also not significant (b=1.154, 95% CI -1.978 to 7.637).
      Between-group differences were small and not significant for all secondary
      outcomes. Adherence to the intervention was low. Only 36% (49/136) received an
      adequate dosage of the intervention (>=4 of 5 sessions). The overall treatment
      satisfaction was moderate. CONCLUSIONS: Internet-based problem solving therapy is
      not more effective in reducing symptoms of depression than receiving an unguided
      self-help book during the waitlist period at outpatient mental health clinics.
      The effect sizes are much smaller than those found in earlier research in the
      general population, and the low rates of adherence indicate that the
      acceptability of the intervention at this stage of treatment for depressed
      outpatients is low. However, taking into account that there is much evidence for
      the efficacy of Internet-based treatments, it is too early to draw firm
      conclusions about the effectiveness of these treatments in outpatient clinics as
      a whole. TRIAL REGISTRATION: Netherlands Trial Register NTR2824;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2824 (Archived by
      WebCite at http://www.webcitation/ 6g3WEuiqH).

PMID- 27032448
TI  - Sex-specific effects of cytotoxic chemotherapy agents cyclophosphamide and
      mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations
      in the prefrontal cortex and hippocampus - an aging connection.
AB  - Recent research shows that chemotherapy agents can be more toxic to healthy brain
      cells than to the target cancer cells. They cause a range of side effects,
      including memory loss and cognitive dysfunction that can persist long after the
      completion of treatment. This condition is known as chemo brain. The molecular
      and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the
      effects of two cytotoxic chemotherapy drugs-cyclophosphamide (CPP) and mitomycin
      C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal
      cortex (PFC) and hippocampal regions. We for the first time showed that CPP and
      MMC treatments led to profound sex- and brain region-specific alterations in gene
      expression profiles. Gene expression changes were most prominent in the PFC
      tissues of female mice 3 weeks after MMC treatment, and the gene expression
      response was much greater for MCC than CPP exposure. MMC exposure resulted in
      oxidative DNA damage, evidenced by accumulation of 8-oxo-2'-deoxyguanosine (8
      oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of
      female animals 3 weeks after treatment. MMC treatment decreased global DNA
      methylation and increased DNA hydroxymethylation in the PFC tissues of female
      mice. The majority of the changes induced by chemotherapy in the PFC tissues of
      female mice resembled those that occur during the brain's aging processes.
      Therefore, our study suggests a link between chemotherapy-induced chemo brain and
      brain aging, and provides an important roadmap for future analysis.

PMID- 27032450
TI  - Are early cannulation arteriovenous grafts (ecAVG) a viable alternative to
      tunnelled central venous catheters (TCVCs)? An observational "virtual study" and
      budget impact analysis.
AB  - BACKGROUND: Early cannulation arteriovenous grafts (ecAVGs) are advocated as an
      alternative to tunnelled central venous catheters (TCVCs). A real-time
      observational "virtual study" and budget impact model was performed to evaluate a
      strategy of ecAVG as a replacement to TCVC as a bridge to definitive access
      creation. METHODOLOGY: Data on complications and access-related bed days was
      collected prospectively for all TCVCs inserted over a six-month period (n = 101).
      The feasibility and acceptability of an alternative strategy (ecAVGs) was also
      evaluated. A budget impact model comparing the two strategies was performed.
      Autologous access in the form of native fistula was the goal wherever possible.
      RESULTS: We found 34.7% (n = 35) of TCVCs developed significant complications
      (including 17 culture-proven bacteraemia and one death from line sepsis).
      Patients spent an average of 11.9 days/patient/year in hospital as a result of
      access-related complications. The wait for TCVC insertion delayed discharge in 35
      patients (median: 6 days). The ecAVGs were a practical and acceptable alternative
      to TCVCs in over 80% of patients. Over a 6-month period, total treatment costs
      per patient wereGBP5882 in the TCVC strategy and GBP4954 in the ecAVG strategy,
      delivering potential savings ofGBP927 per patient. The ecAVGs had higher
      procedure and re-intervention costs (GBP3014 vs. GBP1836); however, these were
      offset by significant reductions in septicaemia treatment costs (GBP1322 vs.
      GBP2176) and in-patient waiting time bed costs (GBP619 vs. GBP1870). CONCLUSIONS:
      Adopting ecAVGs as an alternative to TCVCs in patients requiring immediate access
      for haemodialysis may provide better individual patient care and deliver cost
      savings to the hospital.

PMID- 27032451
TI  - A technique for ultrasound-guided blood sampling from a dry and gel-free puncture
      area.
AB  - PURPOSE: Vein punctures are performed daily to sample blood. Ultrasound (US)
      offers an alternative to the blind landmark technique for difficult vascular
      access. A challenge for this procedure is the presence of US gel in the puncture
      area. We present a technique for US-guided puncture from extremity veins not
      palpable or visible to the human eye, while keeping the puncture area dry and gel
      free. METHODS: Ten healthy volunteers underwent two US-guided vein punctures from
      veins that were neither palpable nor visible. One was drawn from an antebrachial
      vein and another from a brachial vein. A sterile barrier drape was made from a
      commercially available dressing and a piece of transparent sterile plastic. The
      barrier drape consists of an adhesive part placed on the skin designed for
      sonography and a free transparent flap constituting the barrier between the
      unsterile sonographic site and the sterile gel-free puncture site. RESULTS: The
      success rate for vein puncture was 100% in both locations. A total of 22 skin
      punctures were performed (11 antebrachial and 11 brachial). Gain output was
      increased 7% (4-12%), and 8% (4-15%), respectively, to compensate for attenuation
      of the US signal due to the drape. Alignment of the centre of the transducer with
      the long-axis of the target vein during the procedure was reported as a
      challenge. CONCLUSIONS: US-guided blood sampling from a brachial and antebrachial
      vein was possible with a 100% success rate, while ensuring a dry and gel-free
      venipuncture area on one side and the transducer on the other side of a sterile
      barrier.

PMID- 27032452
TI  - Improved arterial exposure and ergonomics with use of elasticated retractors in
      vascular surgery.
AB  - Traditional self-retaining retraction devices do not always provide adequate
      exposure and, on occasion, hamper economy of movement during vascular surgical
      procedures. We report the novel use of elasticated retractors to improve surgical
      exposure for vascular access procedures that may be transferable to other
      vascular surgical procedures. 

PMID- 27032453
TI  - Ankle arteriovenous fistula - a rare site of choice for hemodialysis.
AB  - PURPOSE: Native arteriovenous fistula (AVF) is the ideal vascular access for
      hemodialysis. Once upper extremity vessels are exhausted or not suitable for AVF
      creation, the remaining options were either arteriovenous graft (AVG) or lower
      limb arteriovenous fistula. METHODS: A 45-year-old male patient with chronic
      kidney disease (CKD) stage V was initiated on hemodialysis through a central
      venous catheter. He was referred for AVF creation after failed left radiocephalic
      AVF. In view of poor caliber of upper limb veins and unaffordability of AVG, a
      lower limb AVF was considered. The patient underwent left lower limb AVF creation
      between the great saphenous vein and the posterior tibial artery at the ankle and
      perforator ligation of leg. AVF was cannulated after 6 weeks with achieved blood
      flow rate of 300 mL/min during dialysis. He had been continuing hemodialysis
      through lower limb AVF for almost 12 months at the last follow-up. CONCLUSIONS:
      Ankle AVF could be a viable alternative to the other sites of AVF for CKD in
      patients where upper limb AVF is not possible. This could be an alternative in
      resource-limited settings; however, its long-term patency and complications will
      need to be assessed in large studies.

PMID- 27032454
TI  - Transradial access for visceral endovascular interventions in morbidly obese
      patients: safety and feasibility.
AB  - PURPOSE: Transradial access (TRA) has been shown to lower morbidity and bleeding
      complications compared to transfemoral access in percutaneous coronary
      interventions. Morbid obesity, commonly defined as a body mass index (BMI) >=40
      kg/m2, has been shown to be a risk factor for access site complications
      irrespective of access site. This study evaluates the safety and feasibility of
      performing visceral endovascular interventions in morbidly obese patients via
      TRA. METHODS: Procedural details, technical success, and 30-day major and minor
      access site, bleeding, and neurological adverse events were prospectively
      recorded in a database of 1057 procedures performed via the radial artery. From
      this database we identified 22 visceral interventions performed with TRA in 17
      morbidly obese patients (age: 53 +/- 11 years, female: 71%) with a median BMI of
      42.7 kg/m2. RESULTS: Interventions included radio-embolization (n = 7, 31.8%),
      chemo-embolization (n = 6, 27.3%), uterine fibroid embolization (n = 4, 18.2%),
      renal embolization (n = 2, 9.1%), hepatic embolization (n = 1, 4.5%), lumbar
      artery embolization (n = 1, 4.5%), and renal angioplasty (n = 1, 4.5%). The
      technical success was 100%. There were no major or minor adverse access site,
      bleeding, or neurological complications at 30 days. CONCLUSIONS: This study
      suggests visceral endovascular interventions performed in morbidly obese patients
      are safe and feasible.

PMID- 27032455
TI  - A two-year experience with a rapid access, self-sealing, polycarbonate urethane
      nanofiber vascular access graft for hemodialysis.
AB  - OBJECTIVE: Evaluating the safety and efficacy of the AVfloTM graft in terms of
      patency and complications (early and late) over 2 years. MATERIALS AND METHODS:
      Twelve end-stage renal disease (ESRD) patients (age: mean 68.5 +/- 10 years) were
      followed up for a mean period of 946 +/- 570 days after receiving an implantation
      of the graft for HD. The grafts were implanted at the lower arm (loop
      configuration), upper arm (straight configuration) and the thigh (loop
      configuration). First dialysis was performed at day 7 (3-21) following
      implantation. RESULTS AND DISCUSSION: After a mean follow up of 24 months, the
      primary patency was 56% and the secondary patency was 82%. In this group, AVfloTM
      shows similar if not superior efficacy and safety to that of available grafts in
      terms of safety, complications, and long-term patency.

PMID- 27032456
TI  - Assessment of micro-mechanical variations in experimental arteriovenous fistulae
      using atomic force microscopy.
AB  - PURPOSE: This study presents a method to quantify micro-stiffness variations in
      experimental arteriovenous fistulae (AVF). METHODS: AVF created by anastomosing
      the superficial epigastric vein to the femoral artery in Sprague-Dawley rats were
      allowed to remodel for 21 days before being harvested and preserved in culture
      medium. A custom atomic force microscope was used to measure microvascular
      stiffness (Young's modulus) in three areas of the AVF: the inflow artery, the
      juxta-anastomotic area, and the outflow vein. Morphometric measurements and
      collagen and elastin contents were also determined. RESULTS: Atomic force
      microscopy indentation revealed an increased stiffness in the juxta-anastomotic
      area of the AVF compared to the outflow vein and inflow artery. The juxta
      anastomotic area was also significantly stiffer than the contralateral vein. The
      lack of elasticity (higher Young's modulus) of the juxta-anastomotic region was
      associated with a thicker vascular wall that was rich in collagen but poor in
      elastin. CONCLUSIONS: This study demonstrates for the first time the feasibility
      of using atomic force microscopy to measure local stiffness variations in
      experimental AVF. This technique could be instrumental in advancing our
      understanding of how micro-spatial organization of the AVF wall determines the
      overall biomechanical performance of this type of vascular access.

PMID- 27032457
TI  - Rumen-protected methionine and lysine: effects on milk production and plasma
      amino acids of dairy cows with reference to metabolisable protein status.
AB  - Two experiments were conducted to study the effects of rumen-protected Met (RPM)
      alone or with rumen-protected Lys (RPL) on milk yield and plasma amino acids of
      dairy cows. In experiment 1, 24 multiparous Holstein cows (154 DIM) were assigned
      to one of 3 groups where each cow received 0 g/d of RPM and RPL (C), 30 g/d of
      RPM (M), or 30 g/d of RPM plus 25 g of RPL (ML). The study lasted for 8 weeks
      where milk yield and composition were determined weekly. Daily milk yield
      averaged 28.0, 27.8, and 29.7 kg/cow for the C, M, and ML groups, respectively.
      Dietary treatments had no effects (P >= 0.54) on milk contents of fat, lactose,
      solid non-fat or total solids. Milk protein content in the ML group was greater
      (P < 0.05) than the C and M groups. Plasma levels of all AA were not
      significantly (P >= 0.09) affected by supplemental RPL and/or RPM. In experiment
      2, 30 multiparous Holstein cows (100 DIM) were assigned to one of 3 groups where
      each cow received 0 g/d of RPM and RPL (C), 50 g/d of RPM (M), or 50 g/d of RPM
      plus 25 g/d of RPL (ML). The study lasted for 5 weeks. Cows in the M (30.5 kg)
      and ML (31.4 kg) groups produced (P < 0.05) more milk than those of the C group
      (29.1 kg). Under conditions of this study, RPM plus RPL improved milk yield and
      protein contents of dairy cows and was better than supplying RPM alone. Response
      in milk yield to RPM and RPL was affected by the MP status of cows which deserves
      further investigation. 

PMID- 27032458
TI  - Quarantine for Zika Virus? Where is the Science?
AB  - In January 2016, the World Health Organization warned that Zika virus is
      "spreading explosively" in the Americas and that up to 4 million infections could
      be present worldwide within a year. Soon thereafter, some politicians and authors
      publicly advocated for quarantine of travelers returning from regions where
      mosquitoes carrying Zika virus are prevalent. The public health tool of
      quarantine can be used to prevent the spread of infection by restricting the
      movement of persons who have been exposed to a deadly disease that can be
      transmitted from person to person before symptom onset. With 80% of Zika virus
      infections being asymptomatic, no rapid test being available to detect the virus,
      and primary transmission being via the bites of certain mosquitoes, application
      of quarantine in this setting is not scientifically sound or practically
      feasible. Rather, public health interventions should focus on preventing bites
      from infected mosquitoes, counseling pregnant women on the risks of fetal
      microcephaly and other birth defects, and identifying patients with signs and
      symptoms of Guillain-Barre syndrome. As was seen in the Ebola virus disease
      outbreak of 2014, non-evidence-based factors can influence policy decisions.
      Public health experts must ensure that policy makers are informed that quarantine
      is not a scientifically sound approach for the control of Zika virus. (Disaster
      Med Public Health Preparedness. 2016;0:1-3).

PMID- 27032459
TI  - Diabetic peripheral neuropathy class prediction by multicategory support vector
      machine model: a cross-sectional study.
AB  - OBJECTIVES: Diabetes is increasing in worldwide prevalence, toward epidemic
      levels. Diabetic neuropathy, one of the most common complications of diabetes
      mellitus, is a serious condition that can lead to amputation. This study used a
      multicategory support vector machine (MSVM) to predict diabetic peripheral
      neuropathy severity classified into four categories using patients' demographic
      characteristics and clinical features. METHODS: In this study, the data were
      collected at the Diabetes Center of Hamadan in Iran. Patients were enrolled by
      the convenience sampling method. Six hundred patients were recruited. After
      obtaining informed consent, a questionnaire collecting general information and a
      neuropathy disability score (NDS) questionnaire were administered. The NDS was
      used to classify the severity of the disease. We used MSVM with both one-against
      all and one-against-one methods and three kernel functions, radial basis function
      (RBF), linear, and polynomial, to predict the class of disease with an unbalanced
      dataset. The synthetic minority class oversampling technique algorithm was used
      to improve model performance. To compare the performance of the models, the mean
      of accuracy was used. RESULTS: For predicting diabetic neuropathy, a classifier
      built from a balanced dataset and the RBF kernel function with a one-against-one
      strategy predicted the class to which a patient belonged with about 76% accuracy.
      CONCLUSIONS: The results of this study indicate that, in terms of overall
      classification accuracy, the MSVM model based on a balanced dataset can be useful
      for predicting the severity of diabetic neuropathy, and it should be further
      investigated for the prediction of other diseases.

PMID- 27032460
TI  - Cloning and characterization of metallothionein gene (HcMT) from Halostachys
      caspica and its expression in E. coli.
AB  - Halostachys caspica is a short shrub distributed in the semi-arid and saline
      alkali area, which evolved various mechanisms for modulating salt and metal
      level. In the present study, a Type 2 metallothionein (HcMT) gene was cloned from
      the salt induced suppression subtractive hybridization (SSH) cDNA library of
      H.caspica. Quantitative real time PCR (qRT-PCR) analysis indicated that HcMT gene
      was up-regulated under the stress of Cu(2+), Zn(2+) and Cd(2+), and the tolerance
      of E. coli strain harboring with the recombinant HcMT (pET-32a-HcMT) to Cu(2+),
      Zn(2+) and Cd(2+) was enhanced compared to strain with control vector (pET-32a).
      Moreover, the purified TrxA-HcMT fusion protein from E. coli cells grown in the
      presence of 0.3mM CuSO4, 0.3mM ZnSO4, or 0.1mM CdCl2 could bind more metal ions
      than TrxA alone. The predicted 3D structure showed that HcMT could form a single
      metal-thiolate cluster, which confers the ability to bind five divalent metal
      ions through fourteen cysteine residues. These data indicate that HcMT may be
      involved in processes of metal tolerance in H. caspica and could be employed as a
      potential candidate for heavy metal phytoremediation.

PMID- 27032461
TI  - Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic
      pathways in SH-SY5Y neuroblastoma cells.
AB  - Neuroblastoma is one of the most common types of pediatric tumors that can spread
      quickly in neuronal tissues. Oleuropein which is active compound of olive leaves,
      belongs to polyphenols group and has antioxidant, anti-microbial, anti
      inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the
      study is to determine the therapeutic effects of oleuropein on cell
      proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in
      SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of
      oleuropein on cell viability was determined by XTT method. 84 cell cycle control
      and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on
      apoptosis were researched by TUNEL assay. Protein expressions were determined by
      western blot analysis. Effects of oleuropein on cell invasion, colony formation
      and migration were detected by matrigel-chamber, colony formation assay and wound
      healing assay, respectively. IC50 value of oleuropein in SH-SY5Y cells was
      detected as 350 MUM at 48th hours. It is determined that oleuropein causes cell
      cycle arrest by down-regulating of CylinD1,CylinD2,CyclinD3,CDK4,CDK6 and up
      regulating of p53 and CDKN2A, CDKN2B, CDKN1A gene expressions. Oleuropein also
      induces apoptosis by inhibiting of Bcl-2 and activating of Bax,caspase-9 and
      caspase-3 gene expressions. Apoptotic cell ratio was found 36.4 +/- 3.27% in
      oleuropein dose group. Oleuropein decreased invasion in SH-SY5Y cells and
      suppressed colony numbers in ratio of 53.6 +/- 4.71%.Our results demonstrated
      that oleuropein can be a therapeutic agent in the treatment of neuroblastoma.

PMID- 27032462
TI  - Differential effects of short co-incubation of gametes and early removal of
      cumulus cells in patients with different fertilizing capabilities.
AB  - The objective of this retrospective study was to evaluate the embryological and
      clinical outcomes of short co-incubation of gametes and early removal of cumulus
      cells (SCGERCC) in patients with good IVF capability and those with complete
      fertilization failure treated by rescue intracytoplasmic sperm injection (ICSI).
      The study included 257 couples with >60% fertilization rate (SCGERCC group) in
      the SCGERCC cycle, 72 couples with complete fertilization failure in the SCGERCC
      cycle given early rescue ICSI treatment (early rescue group), and 219 couples who
      underwent IVF cycles with overnight co-incubation of gametes with >60%
      fertilization rate (traditional IVF group). The results showed that the SCGERCC
      group had a higher multi-pronuclei rate (13.34%, P < 0.001) than the early rescue
      ICSI (5.15%) and traditional IVF (6.15%) groups. The good quality embryo rate was
      higher in the SCGERCC group, but implantation, clinical pregnancy and live-birth
      rates (37.21%, 36.92% and 38.20% for SCGERCC, early rescue and traditional IVF
      groups, respectively) were comparable in all three groups. The study indicated
      that SCGERCC followed by rescue ICSI helped couples with initial complete
      fertilization failure attain clinical outcomes comparable with the other two
      groups, but it significantly increased the multi-pronuclei rate in couples with
      good fertilizing capabilities. 

PMID- 27032463
TI  - In vitro potency determination of botulinum neurotoxin B based on its receptor
      binding and proteolytic characteristics.
AB  - Botulinum neurotoxins (BoNTs) are the most potent toxins known. However, the
      paralytic effect caused by BoNT serotypes A and B is taken advantage of to treat
      different forms of dystonia and in cosmetic procedures. Due to the increasing
      areas of application, the demand for BoNTs A and B is rising steadily. Because of
      the high toxicity, it is mandatory to precisely determine the potency of every
      produced BoNT batch, which is usually accomplished by performing toxicity testing
      (LD50 test) in mice. Here we describe an alternative in vitro assay for the
      potency determination of the BoNT serotype B. In this assay, the toxin is first
      bound to its specific receptor molecules. After the proteolytic subunit of the
      toxin has been released and activated by chemical reduction, it is exposed to
      synaptobrevin, its substrate protein. Finally the proteolytic cleavage is
      quantified by an antibody-mediated detection of the neoepitope, reaching a
      detection limit below 0.1mouseLD50/ml. Thus, the assay, named BoNT/B binding and
      cleavage assay (BoNT/B BINACLE), takes into account the binding as well as the
      protease function of the toxin, thereby measuring its biological activity. 

PMID- 27032464
TI  - Influence of Gender and Gender-Specific Recommendations on Adolescent Human
      Papillomavirus Vaccination.
AB  - INTRODUCTION: The human papillomavirus (HPV) vaccine was introduced for female
      adolescents prior to male adolescents. Understanding coverage patterns related to
      gender-specific recommendations and factors associated with early adoption and
      timely completion may be important for future vaccines. METHODS: Retrospective
      analysis of HPV vaccine initiation (one or more dose) and completion (three or
      more doses) patterns in adolescents aged 11-18 years using 2009-2013 New York
      Citywide Immunization Registry data. Log binomial models assessed patient
      specific (age, insurance) and practice-specific (facility type, number of
      adolescents, poverty level) variables on early adoption (within 1 year of
      recommendation) and timely completion (within 12 months) by gender. RESULTS: Of
      1,494,767 adolescents, 50.2% were male, 57.5% were vaccinated in private
      practices, 58.7% in practices with more adolescents, and 48.8% in highest poverty
      locations. More female (54.0%) than male (33.5%) adolescents initiated
      vaccination (p<0.001). Of those, 56.1% received three or more doses, 34.1% within
      12 months (30.0% male, 36.8% female, p<0.001). In 2009-2012, the proportion of
      still-eligible male adolescents who newly initiated increased from 0.1% to 17.0%;
      rates for female adolescents increased from 15.4% to 17.3%. Vaccination
      initiation within 1 year of gender-specific recommendations was similar (27.4%
      female, 27.3% male). For both genders, the uninsured were less likely to have
      early adoption and timely completion. Being publicly insured was associated with
      early adoption in both genders, but with timely completion in male adolescents
      only. Being seen in a public facility and in a practice with more adolescents was
      also associated with early adoption. CONCLUSIONS: Changing HPV vaccine
      recommendations had minimal cross-gender impact. Early adoption and timely
      completion patterns were mostly similar across genders.

PMID- 27032465
TI  - Brucellosis vaccines for livestock.
AB  - Brucellosis is a livestock disease responsible for fetal loss due to abortions.
      Worldwide, this disease has profound economic and social impact by reducing the
      ability of livestock producers to provide an adequate supply of disease-free meat
      and dairy products. In addition to its presence in domesticated animals,
      brucellosis is harbored in a number of wildlife species creating new disease
      reservoirs, which adds to the difficulty of eradicating this disease. Broad and
      consistent use of the available vaccines would contribute in reducing the
      incidence of brucellosis. Unfortunately, this practice is not common. In
      addition, the current brucellosis vaccines cannot provide sterilizing immunity,
      and in certain circumstances, vaccinated livestock are not protected against co
      mingling Brucella-infected wildlife. Given that these vaccines are inadequate for
      conferring complete protection for some vaccinated livestock, alternatives are
      being sought, and these include genetic modifications of current vaccines or
      their reformulations. Alternatively, many groups have sought to develop new
      vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus
      adjuvant or the heterologous expression of Brucella epitopes by different vaccine
      vectors are currently being tested. New live attenuated Brucella vaccines are
      also being developed and tested in their natural hosts. Yet, what is rarely
      considered is the route of vaccination which could improve vaccine efficacy.
      Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a
      vaccine has the potential of eliciting a more robust protective immune response
      for improved efficacy. Hence, this review will examine these questions and
      provide the status of new vaccines for livestock brucellosis.

PMID- 27032466
TI  - [Prevalence of human papillomavirus infection in squamous cell carcinoma of the
      oral cavity, oropharynx and larynx].
AB  - BACKGROUND: Cancer of the head and neck comprises a group of neoplasms that share
      a similar anatomical origin. Most originate from the epithelium of the
      aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15
      years, an increase in the incidence of squamous cell carcinoma induced by human
      papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most
      frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11
      in laryngeal cancer. There are reports in the literature that show HPV as the
      leading cause of oropharyngeal squamous cell carcinoma. OBJECTIVE: Determine the
      prevalence of infection with high-risk HPV in patients diagnosed with squamous
      cell carcinoma of the oral cavity, oropharynx and larynx. MATERIAL AND METHODS:
      An observational, cross-sectional, descriptive, unblinded study was performed.
      Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in
      DNA samples from tumour tissue of patients with squamous cell carcinoma of the
      oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV
      positive samples in order to detect types 18, 16, 11 and 6, using custom primers.
      RESULTS: A total of 45 patients were included. The association between laryngeal
      squamous cell carcinoma and HPV was established in two patients, which
      represented an overall prevalence of 4.4% in our population, and 10% for
      laringeal tumours. CONCLUSIONS: There is a low prevalence of HPV infection in
      squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our
      population. Prospective studies on younger patients could provide more
      information.

PMID- 27032467
TI  - Discrepancy of epidermal growth factor receptor mutation in lung adenocarcinoma
      presenting as multiple ground-glass opacities.
AB  - OBJECTIVES: To identify epidermal growth factor receptor (EGFR) mutation status
      between different lesions in lung adenocarcinoma presenting as multiple ground
      glass opacity (GGO) lesions and analyse its association with clinical
      characteristics. METHODS: Seventy-eight patients with lung adenocarcinoma
      presenting as multiple GGO lesions were identified to investigate EGFR mutation
      in exon 18-21. Lesions with the largest size in diameter were defined as the
      primary lesions; the others were defined as the secondary lesions. One hundred
      and fifty-nine lesions of these patients were classified into pure GGO and mixed
      GGO by computed tomography scan images. RESULTS: The EGFR mutation rate in the
      patients was 48.7% (38 of 78). Patients with high frequency of EGFR mutation were
      females and non-smokers. The EGFR mutation rate of invasive adenocarcinoma was
      higher than that of atypical adenomatous hyperplasia/adenocarcinoma in situ and
      minimally invasive adenocarcinoma (P = 0.001). Although 19-deletion and L858R
      were the most common EGFR mutations, there was no difference of EGFR mutation in
      pathological subtypes of adenocarcinoma. Of the 38 paired lesions in patients
      harbouring EGFR mutation, the discordance rate of EGFR mutation was 92.1%.
      CONCLUSIONS: The study showed different EGFR mutational profiles in multiple GGO
      lesions, suggesting that lesions seem to arise as independent events. It would
      offer useful information for determining the appropriate treatment strategy for
      lung adenocarcinoma presenting as multiple GGO lesions.

PMID- 27032468
TI  - Modified Blalock-Taussig shunt: simple but unpredictable.

PMID- 27032469
TI  - Expectations and limitations after bilateral pulmonary artery banding.
AB  - OBJECTIVES: Bilateral pulmonary artery banding (bil-PAB) has been developed as a
      part of a hybrid procedure for hypoplastic left heart syndrome (HLHS). We use
      this procedure for palliation of complex congenital heart disease, particularly
      in patients with arch anomaly. We reviewed our experience with bil-PAB. METHODS:
      Sixty-six consecutive cases between 2003 and 2014 were reviewed retrospectively.
      RESULTS: Fifty-one patients (77%) had single ventricle physiology (HLHS: 37, HLHS
      variant: 13, others: 1). Twelve patients had biventricular physiology [5
      interrupted aortic arch with ventricular septal defect (VSD); 4 coarctation of
      the aorta with VSD; 2 truncus arteriosus; 1 other]. In 3 patients, it was
      difficult to determine if the physiology was single ventricle or biventricle due
      to borderline left ventricle size. Age and body weight at the time of operation
      were 4.3 +/- 3.4 days and 2.7 +/- 0.5 kg, respectively. Overall hospital
      mortality was 11% (7/66). Of the 42 patients from 2010, only 1 with multiple
      anomalies died between bil-PAB and the second-stage operation. Thirteen patients
      (20%) required reoperation of bil-PAB. The mean waiting time for the next
      operation was 44.3 +/- 42.8 days. The body weight at the second-stage operation
      was 3.2 +/- 0.8 kg. Seven (11%) patients developed patent ductus arteriosus
      obstruction during the waiting period. Twenty-four patients were 2.5 kg or less;
      20 patients in this group progressed to the second-stage operation and of these
      19 gained body weight. Forty-two patients were above 2.5 kg, but of these only 23
      patients gained body weight. Ten patients underwent bil-PAB because of shock and
      8 of these recovered from shock. In 2 borderline cases, the patients underwent
      the Norwood procedure and 1 patient had arch repair and VSD closure. CONCLUSIONS:
      Bil-PAB could be applied to a wide variety of complex diseases. Our mortality
      rates with bil-PAB improved significantly post-2010. Good indications for bil-PAB
      were shock and situations where it was unclear whether the physiology was single
      ventricle or biventricular. Body weight gain was difficult to predict, but
      patients weighing less than 2.5 kg could be expected to gain body weight after
      the procedure.

PMID- 27032470
TI  - Era effect on survival following paediatric heart transplantation.
AB  - OBJECTIVES: Paediatric heart transplantation is performed to salvage children
      with end-stage heart failure from various underlying pathologies. Despite several
      developments in all management aspects of transplantation candidates, the effect
      of those advances on outcomes has not been consistent. We report our
      institutional experience with focus on examining era effect on early and late
      survival. METHODS: Between 1988 and 2015, 320 children underwent heart
      transplantation. Competing risk analysis modelled events after transplantation
      (retransplantation, death without retransplantation). Multivariable parametric
      risk hazard analysis examined the risk factors affecting survival. RESULTS:
      Patients were divided to three groups based on underlying pathology: congenital
      group (n = 132, 41%), acquired group (n = 153, 48%) and retransplant group (n =
      35, 11%). Competing risk analysis showed that at 10 years following
      transplantation, 11% of patients had undergone retransplantation, 39% had died
      without retransplantation and 44% were alive without retransplantation. Ten-year
      survival was 61, 51 and 45% for acquired, congenital and retransplant groups,
      respectively. Overall, survival following heart transplantation for the late era
      (2005-15) was 63% compared with 49% for the early era (1988-2004) at 10 years (P
      = 0.022). Compared with early era, 1-year survival in the late era was 84 vs 79%
      {odds ratio (OR): 0.72 [95% confidence interval (CI) 0.3-1.8], P = 0.470} for
      congenital, 98 vs 86% [OR: 0.14 (95% CI 0.03-0.68), P = 0.006] for acquired and
      73 vs 88% [OR: 2.6 (95% CI 0.4-1.9), P = 0.282] for retransplant. The effect of
      late era on survival was not significant for congenital [hazard ratio (HR) 0.6
      (95% CI 0.2-1.4), P = 0.206] or retransplant patients [HR: 1.7 (95% CI 0.5-5.5),
      P = 0.400], but showed improvement trend for acquired patients [HR: 0.53 (95% CI
      0.3-1.0), P = 0.052]. CONCLUSIONS: The era effect on early survival following
      heart transplantation is related to underlying pathology; there is a significant
      improvement in early survival in children with acquired pathology, whereas there
      is no significant change in early survival in children with congenital pathology
      or failed prior transplantation. This suggests a potential area for improvement
      that might include pretransplant stabilization and management of
      immunosuppression. On the other hand, era effect on late survival is not
      significant. This demonstrates that advances in the care of paediatric heart
      transplantation patients have not affected ongoing problems that diminish late
      survival.

PMID- 27032471
TI  - Results of surgical treatment and impact on T staging of non-small-cell lung
      cancer adjacent lobe invasion.
AB  - OBJECTIVES: To assess the results of surgical treatment of T-ALI (adjacent lobe
      invasion) tumours in patients with non-small-cell lung carcinoma. METHODS:
      Multicentric retrospective analysis of a prospectively maintained database of 13
      065 patients, aged 32-89 years (mean 52.9, median 63 years), who underwent
      resection between January 2009 and September 2014. RESULTS: In the whole study
      group, T-ALI was observed in 324 patients (2.5%): 201 patients (62.0%) with a
      tumour invading the pleura in the inter-lobar fissure (T-ALI-A), and 123 patients
      (38.0%) with a tumour in the adjacent lobe but without pleural invasion in the
      fissure (T-ALI-D). With regard to N0 patients, the 3- and 5-year survival rates
      in the T2 group were significantly higher than that of the T-ALI group (76.1 and
      68.4%, P = 0.002 vs 58.3 and 51.0%, P = 0.008, respectively). On the other hand,
      when the N1 group was analysed, the 5-year survival rates were 54.3 and 48%,
      respectively (P = 0.041). In the N2 group, the 5-year survival rates in the T2
      and T-ALI groups were 40.2 and 35.0%, respectively (P = 0.241). The comparison of
      the T-ALI and T3 groups for stages N0, N1 and N2 revealed differences in 5-year
      survival rates as follows: 68.4 vs 62.9% (P = 0.048), 48.0 vs 37.6% (P = 0.08)
      and 35.0 vs 27.6% (P = 0.121), respectively. In the whole group, the difference
      in survival rate between T-ALI N0 and T2N0 was statistically significant (P =
      0.008) and statistically significant for the T3N0 group (P = 0.048). The 3-year
      survival rate in the T-ALI N0 group was statistically lower following
      pneumonectomy than following lobectomy (56.4 vs 61.3%, P = 0.03). The best
      survival rate was observed following bilobectomy (75.6%). CONCLUSIONS: In our
      study, a tumour with ALI (T-ALI) represented a separate stage of cancer between
      T2 and T3. The survival rate in the T-ALI-A group was significantly poorer than
      that in the T-ALI-D group. Overall treatment results were similar for stage T3,
      suggesting that it may be necessary to divide this group into T3a and T3b. We
      would suggest that all tumours between 5 and 7 cm be classified as T3b, and any
      tumour smaller than 5 cm but with ALI be classified as T3a. Treatment of choice
      should include lobectomy or bilobectomy. Pneumonectomy should be performed only
      in a selected group of patients.

PMID- 27032472
TI  - Endovascular resection of the native aortic valve before transcatheter aortic
      valve implantation: state of the art and review.
AB  - Transcatheter aortic valve implantation was introduced into clinical practice in
      2002 as a rescue approach in patients presenting with symptomatic severe aortic
      stenosis but not eligible for conventional aortic valve replacement. This
      technique allows implantation of a balloon expandable bioprosthesis without
      resection of the native aortic valve. Several complications are described as a
      consequence of the residual highly calcified valve being squeezed against the
      aortic wall by the stent of the implant. This can result in deformation of the
      metal stent and paravalvular leakage, risk of occlusion of the coronary ostia, or
      central and peripheral embolization of valvular debris. To avoid these
      complications, many authors suggest the possibility to resect and remove the
      native aortic valve before transcatheter aortic valve implantation. In this
      field, different authors have described possible techniques and different sources
      of energy to resect the calcified valve. In this article, we review the
      development of these experimental techniques and discuss future prospects in this
      field. 

PMID- 27032473
TI  - Comparison of outcomes between neuroendocrine thymic tumours and other subtypes
      of thymic carcinomas: a joint analysis of the European Society of Thoracic
      Surgeons and the International Thymic Malignancy Interest Group.
AB  - OBJECTIVES: The latest World Health Organization (WHO) histological
      classification divides thymic epithelial tumours in thymomas and thymic
      carcinomas (TCs), the latter also including the neuroendocrine thymic tumours
      (NETTs). NETTs and other TC histotypes have been described to have a
      significantly lower survival than thymomas, but these two groups of tumours have
      rarely been compared directly. Using the European Society of Thoracic Surgeons
      and the International Thymic Malignancy Interest Group datasets, we wanted to
      study this issue. METHODS: This is a retrospective multicentre cohort study of
      patients operated for TC. Outcome measures were overall survival (OS) and
      recurrence-free survival (RFS). OS was analysed using the Kaplan-Meier method and
      RFS was assessed using competing risk analysis. The association with clinical and
      prognostic factors for OS and RFS was evaluated with log-rank test and Gray's
      test, respectively. RESULTS: A total of 1247 tumours (1042 TCs) were collected
      between 1984 and 2012. A R0 resection was performed in 363 TCs and in 52 NETTs.
      The median follow-up was 4.4 years for TCs and 4.1 years for NETTs. Owing to the
      missing values for survival information, a total of 728 TC patients and 132 NETTs
      were included in the OS analysis. Among them, 262 TC and 39 NETT patients died.
      The median OS was 6.6 years for TC and 7.5 years for NETTs. The overall 5-year
      survival rates were 60% for TC and 68% for NETTs; 10-year survival rates were 40%
      for TCs and 39% for NETTs (P = 0.19). Five-year RFS was 0.35 and 0.34 for TCs and
      NETTs (P = 0.36). On multivariate analysis, histology did not influence either OS
      (P = 0.79) or RFS (P = 0.59). CONCLUSIONS: This represents the largest clinical
      series of TCs and NETTs collected. Despite the biological aggressiveness of these
      rare neoplasms, the 5-year survival rate after resection is over 60% and TCs and
      NETT showed a similar rate of survival and recurrences after surgery.

PMID- 27032474
TI  - Personalized external aortic root support: a review of the current status.
AB  - Personalized external aortic root support (PEARS) is an emerging technology. It
      is a pre-emptive operation to halt aortic root expansion and maintain aortic
      valve function in Marfan syndrome and is also applicable to aortic root aneurysms
      of other aetiologies. To fully evaluate PEARS, awareness of all those who advise
      these patients is necessary to ensure that patients are fully informed of the
      alternative operations, to carefully build experience, to ensure safety and
      quality and to monitor outcomes. Herein, we present a summary of published
      methods and outcomes and the arrangements in place for fuller evaluation. 

PMID- 27032475
TI  - Evolution of mammalian sound localization circuits: A developmental perspective.
AB  - Localization of sound sources is a central aspect of auditory processing. A
      unique feature of mammals is the smooth, tonotopically organized extension of the
      hearing range to high frequencies (HF) above 10kHz, which likely induced positive
      selection for novel mechanisms of sound localization. How this change in the
      auditory periphery is accompanied by changes in the central auditory system is
      unresolved. I will argue that the major VGlut2(+) excitatory projection neurons
      of sound localization circuits (dorsal cochlear nucleus (DCN), lateral and medial
      superior olive (LSO and MSO)) represent serial homologs with modifications, thus
      being paramorphs. This assumption is based on common embryonic origin from an
      Atoh1(+)/Wnt1(+) cell lineage in the rhombic lip of r5, same cell birth, a
      fusiform cell morphology, shared genetic components such as Lhx2 and Lhx9
      transcription factors, and similar projection patterns. Such a parsimonious
      evolutionary mechanism likely accelerated the emergence of neurons for sound
      localization in all three dimensions. Genetic analyses indicate that auditory
      nuclei in fish, birds, and mammals receive contributions from the same progenitor
      lineages. Anatomical and physiological differences and the independent evolution
      of tympanic ears in vertebrate groups, however, argue for convergent evolution of
      sound localization circuits in tetrapods (amphibians, reptiles, birds, and
      mammals). These disparate findings are discussed in the context of the genetic
      architecture of the developing hindbrain, which facilitates convergent evolution.
      Yet, it will be critical to decipher the gene regulatory networks underlying
      development of auditory neurons across vertebrates to explore the possibility of
      homologous neuronal populations.

PMID- 27032476
TI  - Event-related potentials demonstrate deficits in acoustic segmentation in
      schizophrenia.
AB  - Segmentation of the acoustic environment into discrete percepts is an important
      facet of auditory scene analysis (ASA). Segmentation of auditory stimuli into
      perceptually meaningful and localizable groups is central to ASA in everyday
      situations; for example, separation of discrete words from continuous sentences
      when processing language. This is particularly relevant to schizophrenia, where
      deficits in perceptual organization have been linked to symptoms and cognitive
      dysfunction. Here we examined event-related potentials in response to grouped
      tones to elucidate schizophrenia-related differences in acoustic segmentation. We
      report for the first time in healthy subjects a sustained potential that begins
      with group initiation and ends with the last tone of the group. These potentials
      were reduced in schizophrenia, with the greatest differences in responses to
      first and final tones. Importantly, reductions in sustained potentials in
      schizophrenia patients were associated with greater negative symptoms and
      deficits in IQ, working memory, learning, and social cognition. These results
      suggest deficits in auditory pattern segmentation in schizophrenia may compound
      deficits in many higher-order facets of the disorder. 

PMID- 27032477
TI  - Oxidative state and oxidative metabolism of the heart from rats with adjuvant
      induced arthritis.
AB  - The aim of the present work was to investigate, in a more extensive way, the
      oxidative state and parameters related to energy metabolism of the heart tissue
      of rats using the model of adjuvant-induced arthritis. The latter is a model for
      the human arthritic disease. Measurements were done in the total tissue
      homogenate, isolated mitochondria and cytosolic fraction. The adjuvant-induced
      arthritis caused several modifications in the oxidative state of the heart which,
      in general, indicate an increased oxidative stress (+80% reactive oxygen
      species), protein damage (+53% protein carbonyls) and lipid damage (+63%
      peroxidation) in the whole tissue. The distribution of these changes over the
      various cell compartments was frequently unequal. For example, protein carbonyls
      were increased in the whole tissue and in the cytosol, but not in the
      mitochondria. No changes in GSH content of the whole tissue were found, but it
      was increased in the mitochondria (+33%) and decreased in the cytosol (-19%). The
      activity of succinate dehydrogenase was 77% stimulated by arthritis; the
      activities of glutamate dehydrogenase, isocitrate dehydrogenase and cytochrome c
      oxidase were diminished by 31, 25 and 35.3%, respectively. In spite of these
      alterations, no changes in the mitochondrial respiratory activity and in the
      efficiency of energy transduction were found. It can be concluded that the
      adjuvant-induced arthritis in rats causes oxidative damage to the heart with an
      unequal intracellular distribution. Compared to the liver and brain the
      modifications caused by arthritis in the heart are less pronounced on variables
      such as GSH levels and protein integrity. Possibly this occurs because the
      antioxidant system of the heart is less impaired by arthritis than that reported
      for the former tissues. Even so, the modifications caused by arthritis represent
      an imbalanced situation that probably contributes to the cardiac symptoms of the
      arthritis disease.

PMID- 27032478
TI  - Signal exchange and integration during self-fusion in filamentous fungi.
AB  - Growth and propagation of filamentous ascomycete fungi commonly involves
      vegetative cell fusion. In the red bread mold Neurospora crassa and many other
      ascomycete species, fusion occurs between germinating spores during colony
      formation and between hyphal branches in established mycelia. Both fusion
      processes promote the development and behavior of the fungal colony as a supra
      cellular network. Germling and hyphal fusion in N. crassa rely on an unusual mode
      of cellular communication, in which the two fusion partners likely alternate
      between signal emission and reception, thereby establishing a kind of "cell
      dialog". In recent years, numerous molecular factors mediating this unique
      cellular behavior have been identified, including several conserved signal
      transmission pathways, as well as proteins specific for ascomycete fungi.
      Analysis of their molecular interactions revealed the presence of an intricate
      signaling network, whose sophisticated interconnections are still unfolding.
      Despite this complexity, germling and hyphal fusion provide experimentally easily
      amenable model systems and might therefore advance as paradigms for signal
      transmission and cell fusion. In this article, we strive to highlight some of the
      recent advances in this field of research and to discuss the current working
      model of the "cell dialog".

PMID- 27032479
TI  - Virulence-specific cell cycle and morphogenesis connections in pathogenic fungi.
AB  - To initiate pathogenic development, pathogenic fungi respond to a set of
      inductive cues. Some of them are of an extracellular nature (environmental
      signals), while others are intracellular (developmental signals). These signals
      must be integrated into a single response whose major outcome is changes in the
      morphogenesis of the fungus. The regulation of the cell cycle is pivotal during
      these cellular differentiation steps; therefore, cell cycle regulation would
      likely provide control points for infectious development by fungal pathogens.
      Here, we provide clues to understanding how the control of the cell cycle is
      integrated with the morphogenesis program in pathogenic fungi, and we review
      current examples that support these connections.

PMID- 27032480
TI  - Amino acid-based anti-fouling functionalization of silica nanoparticles using
      divinyl sulfone.
AB  - Natural amino acids are zwitterionic molecules and the good biocompatibility
      promises them potential candidates as anti-fouling materials. Here, we developed
      a new method to functionalize silica nanoparticles with a natural amino acid
      based anti-fouling layer. Amino acids were covalently immobilized on 3
      aminopropyltriethoxysilane modified silica nanoparticles using divinyl sulfone
      through a two-step reaction in aqueous solution at room temperature. The progress
      was monitored with NMR, X-ray photoelectron spectroscopy (XPS), transmission
      electron microscope (TEM) and zeta potential measurements. A library of amino
      acids was screened and the nonspecific protein adsorption of bovine serum albumin
      (BSA) and fetal bovine serum (FBS) were investigated using dynamic light
      scattering method. The results showed that cysteine, lysine and arginine
      functionalized silica nanoparticles can effectively resist protein adsorption due
      to the zwitterionic structure. Among them, lysine functionalized silica
      nanoparticles had the best anti-fouling performance, which showed hydrodynamic
      diameter increases of only 10% after incubated in BSA solution and 20% after
      incubated in FBS solution for 24h. The neat aqueous modification process can
      conveniently create a thin zwitterionic layer on silica particles, and it has a
      great potential in biomolecule immobilization and biofunctional surface
      preparation. STATEMENT OF SIGNIFICANCE: Zwitterionic polymer is an outstanding
      class of anti-fouling material; but the difficulty in synthesis is challenging
      its spread utilization. In this study, we developed a new method to create an
      amino acid-based zwitterionic layer on APTES functionalized silica nanoparticles
      through a two-step reaction in aqueous solution at room temperature. The surface
      chemistry was monitored with NMR, XPS, TEM and zeta potential measurements. With
      this method, a library of amino acid conjugated-silica nanoparticles was
      synthesized and their anti-fouling performance was evaluated using dynamic light
      scattering method. The results showed that the cysteine, lysine and arginine
      conjugated nanoparticles all can effectively resist nonspecific protein
      adsorption. Among them, lysine conjugated nanoparticles show the best anti
      fouling performance, which showed hydrodynamic diameter increases of only 10%
      after incubated in BSA solution and 20% after incubated in FBS solution for 24
      hours. These results indicates that the anti-fouling silica nanoparticles are of
      great potential in many biomedical applications, especially biosensing and
      diagnose imaging. The modification reactions in aqueous solution at room
      temperature are easily conducted in laboratory, indicating high potential in the
      functionalization of silica particles/surfaces with other biomolecules.

PMID- 27032481
TI  - Profile of patients with mild-to-moderate acne in Europe: a survey.
AB  - Although acne is almost universal in teenagers, few large cohort studies have
      investigated the profile of acne patients. To identify the profile of European
      patients with mild-to-moderate acne. an epidemiological study was performed using
      inclusion data from a prospective, international, observational phase IV study
      conducted in patients prescribed an anti-acne cream containing retinaldehyde,
      glycolic acid, modified rhamnose and Avene Thermal Spring Water. A total of 2926
      patients (73.1% female) with mild to moderate acne (mean Global Evaluation of
      Acne score of 2.55 +/- 0.7), aged 22.5 +/- 8.0 years, were included in France,
      Switzerland, Italy and Portugal. A family history of acne was present in 62.9% of
      patients and mean age at acne onset was 16.0 +/- 4.9 years. In total, 69.6% of
      patients had moderate to severe hyperseborrhoea, 35.6% acne lesions on both face
      and trunk, 23.6% facial pigmentation and 46% scars. The extent of acne was
      significantly associated with sex, age at acne onset, history of acne and
      presence of scars. In women, acne onset was delayed (p<0.0001) and a family
      history of acne and extension to the trunk were less common than in men (p =
      0.0118, and p<0.0001), as were scars (p = 0.0042). In subjects with a family
      history of acne, the frequency in men was higher (p = 0.0118), acne onset was
      earlier (p<0.0001) and extension to the trunk and presence of scars were more
      common (both p<0.0001). Further epidemiological studies would help define
      specific risk factors for acne occurrence or progression, which may be modified. 

PMID- 27032482
TI  - [The clinical impact of treatment discrepancies recorded for 200 patients in an
      acute geriatric unit].
AB  - INTRODUCTION: Medication reconciliation is a process used to identify and prevent
      medication errors at care transition points in hospitals. The present study's
      main objectives were to quantify the frequency of inadvertent discrepancies (IDs)
      per patient and estimate the seriousness of the IDs' clinical impact. PATIENTS
      AND METHODS: This was a prospective, single-center study performed in a 38-bed
      acute geriatric unit. All patients hospitalized over a 70-day period were
      included in the study. RESULTS: Over a 70-day period, 200 patients were included
      (mean+/-SD age: 85.5+/-5.9). A total of 316 IDs were recorded in 117 patients
      (58.5%, i.e. 1.58 per patient). One third of the IDs were considered to be
      serious or even life-threatening. Omission was the most common type of ID (58%).
      Cardiovascular drugs were most frequently involved in IDs (33%). CONCLUSION: We
      observed an average of more than one ID per patient, when comparing drug
      treatment at home and drug treatment upon admission to hospital. A third of these
      IDs may be clinically significant. Geriatric populations with polypharmacy and
      multiple comorbidities are particularly sensitive to this type of error.
      Medication reconciliation can detect and correct IDs. Collaboration between
      physicians and pharmacists will improve the quality of patient care and reduce
      the iatrogenic risk.

PMID- 27032483
TI  - [Relevance of eosinopenia as marker of sepsis in the Emergency Department].
AB  - BACKGROUND: Several studies in internal medicine departments and in intensive
      care units have shown the interest of eosinopenia in the diagnosis of infected
      patients. The aim of the present study was to test the value of this marker in
      the Emergency Department (ED), either alone or associated with other common
      sepsis markers. METHODS: We report on a retrospective and monocentric study. We
      reviewed the complete blood count (CBC) of all patients visiting the ED during
      one-week duration (in February 2014). Every element of the CBC and other
      inflammation markers (such as CRP) were analyzed. RESULTS: During the week of our
      study, 725 patients had a CBC (33 exclusions) and 692 patients were included for
      analysis. The median age was 59 years (IQR: 16-100). One hundred and twenty-five
      patients (18.1%) had a sepsis. The ROC curve demonstrated a cut off level of
      10/mm3 eosinophils for which the specificity for sepsis was 91%. The association
      of eosinopenia (< 10/mm3) and white blood cells (WBC) or CRP elevation also
      showed a good specificity in patients with sepsis. CONCLUSION: In the ED, with a
      "simple" CBC, a profound eosinopenia appears to be very specific for sepsis,
      alone or in association with other markers of inflammation. Eosinopenia may
      become a helpful tool in our daily practice in the ED. Further studies are needed
      to further evaluate this marker.

PMID- 27032484
TI  - [Diagnosis and treatment of urea cycle disorders in adult patients].
AB  - Urea cycle disorders (UCDs) are inborn errors of metabolism in which the clinical
      picture is mostly due to ammonia intoxication. UCD onset may be observed at any
      age. Acute decompensations of UCDs include neuro-psychiatric symptoms such as
      headache, confusion, convulsions, ataxia, agitation or delirium, as well as
      digestive symptoms, namely nausea and vomiting along with abdominal pain. Acute
      decompensations may lead to an irreversible coma in the absence of specific
      therapy. The first step is to measure promptly ammonemia in such patients, and
      start appropriate therapy on an emergency basis.

PMID- 27032485
TI  - [Zika virus in a New World].

PMID- 27032486
TI  - [Septic shock secondary to non-congenital chikungunya fever in a young infant: A
      clinical case].
AB  - INTRODUCTION: A chikungunya outbreak took place in the State of Yucatan starting
      in the second half of 2015 OBJECTIVE: To analyse the clinical course of a case of
      chikungunya in a previously healthy infant, providing practical evidence to guide
      future diagnoses and treatment during outbreak seasons in endemic areas CASE
      REPORT: Clinical manifestation started with a sudden onset of fever and a diffuse
      macular-papillary erythema, originally treated in the community with non
      steroidal anti-inflammatory drugs. Two days later, the fever relapsed with
      hypoactivity, severe thrombocytopenia and neutropenia (without lymphopenia),
      respiratory distress, liver dysfunction, sepsis, followed by septic shock with a
      fatal outcome. IgM test was positive to chikungunya, while her mother tested
      negative. Pseudomonas aeruginosa was isolated from the blood culture possible due
      to contamination, without ruling out the possibility of a mixed origin sepsis.
      CONCLUSIONS: Chikungunya is a disease in which the manifestations in neonates and
      young infants can be severe, and even fatal. It is important to suspect it in
      this age group at risk of vector contact, in the presence of fever without
      apparent source of infection and cutaneous manifestations. It is important to use
      the antipyretics cautiously, considering the possibility of aggravating the
      underlying infection, and the potential hepatic and haematological damage.

PMID- 27032488
TI  - Polysaccharide extraction from Sphallerocarpus gracilis roots by response surface
      methodology.
AB  - The extraction process of Sphallerocarpus gracilis root polysaccharides (SGRP)
      was optimized using response surface methodology with two methods [hot-water
      extraction (HWE) and ultrasonic-assisted extraction (UAE)]. The antioxidant
      activities of SGRP were determined, and the structural features of the untreated
      materials (HWE residue and UAE residue) and the extracted polysaccharides were
      compared by scanning electron microscopy. Results showed that the optimal UAE
      conditions were extraction temperature of 81 degrees C, extraction time of 1.7h,
      liquid-solid ratio of 17ml/g, ultrasonic power of 300W and three extraction
      cycles. The optimal HWE conditions were 93 degrees C extraction temperature, 3.6h
      extraction time, 21ml/g liquid-solid ratio and three extraction cycles. UAE
      offered a higher extraction yield with a shorter time, lower temperature and a
      lower solvent consumption compared with HWE, and the extracted polysaccharides
      possessed a higher antioxidant capacity. Therefore, UAE could be used as an
      alternative to conventional HWE for SGRP extraction. 

PMID- 27032487
TI  - Changes in Adolescents' Receipt of Sex Education, 2006-2013.
AB  - PURPOSE: Updated estimates of adolescents' receipt of sex education are needed to
      monitor changing access to information. METHODS: Using nationally representative
      data from the 2006-2010 and 2011-2013 National Survey of Family Growth, we
      estimated changes over time in adolescents' receipt of sex education from formal
      sources and from parents and differentials in these trends by adolescents'
      gender, race/ethnicity, age, and place of residence. RESULTS: Between 2006-2010
      and 2011-2013, there were significant declines in adolescent females' receipt of
      formal instruction about birth control (70% to 60%), saying no to sex (89% to
      82%), sexually transmitted disease (94% to 90%), and HIV/AIDS (89% to 86%). There
      was a significant decline in males' receipt of instruction about birth control
      (61% to 55%). Declines were concentrated among adolescents living in
      nonmetropolitan areas. The proportion of adolescents talking with their parents
      about sex education topics did not change significantly. Twenty-one percent of
      females and 35% of males did not receive instruction about methods of birth
      control from either formal sources or a parent. CONCLUSIONS: Declines in receipt
      of formal sex education and low rates of parental communication may leave
      adolescents without instruction, particularly in nonmetropolitan areas. More
      effort is needed to understand this decline and to explore adolescents' potential
      other sources of reproductive health information.

PMID- 27032489
TI  - Nano-encapsulation of capsaicin on lipid vesicle and evaluation of their
      hepatocellular protective effect.
AB  - The intention of the study was to evaluate the effectiveness of nanocapsulated
      food constituent capsaicin in protection of liver oxidative stress. We had
      prepared phospholipid vesicle (nanoliposome) by formation of thin lipid film
      followed by hydration when the mean vesicle diameter was found to be 277.7nm.
      Protection from sodium fluoride (NaF) induced oxidative stress by capsaicin
      loaded nanoliposomal formulation were tested in rats where a single dose of
      capsaicin in free and nanoliposome forms were administered after two hour of
      exposure to NaF. Membrane in hepatic cells were damaged by NaF and it was
      evaluated by estimating reactive oxygen species (ROS), lipid peroxidation, and
      catalase activity when it was observed that free capsaicin produced mild
      protection whereas liposomal capsaicin exerted a significant result. This can be
      suggested that liposome encapsulating capsaicin acts as a promising therapeutic
      agent in reducing liver oxidative stress produced by different stress factors. 

PMID- 27032490
TI  - Structural study on methacrylamide-grafted Tussah silk fibroin fibres.
AB  - Tussah silk fibroin fibres were modified by grafting with methacrylamide (MAA),
      with weight gains ranging between 2.6% and 71.4%. Raman and IR spectroscopic
      analyses showed that upon grafting the fibres underwent slight conformational
      changes towards a more unordered state, due to the covalent and hydrogen bonds
      interactions occurring between the polymer (polyMAA) and the amorphous domains of
      silk fibres. To test the stability towards alkaline hydrolysis, the untreated and
      MAA-grafted silk fibres (weight gain of 71.4%) were immersed in NaOH 5% at 50
      degrees C for different times; the IR and Raman spectroscopic techniques were
      utilized to elucidate the degradation mechanism as well as the rearrangements of
      the fibres induced by the treatment. Upon hydrolysis, both the untreated and
      grafted fibres underwent an enrichment in beta-sheet conformation, due to the
      preferential removal of the unordered domains. As a result of the covalent
      interactions with silk fibroin, the polymer increased its stability towards
      alkaline hydrolysis, since its complete solubilization was avoided and the
      transformation of its CONH2 groups into COO(-) and COOH was delayed. Vibrational
      spectroscopy proved to be a valid technique to investigate the mechanism and the
      effects of the hydrolytic attack, which are both fundamental to design new
      generation silk-based materials. 

PMID- 27032491
TI  - The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day
      Humans.
AB  - Some present-day humans derive up to ~5% [1] of their ancestry from archaic
      Denisovans, an even larger proportion than the ~2% from Neanderthals [2]. We
      developed methods that can disambiguate the locations of segments of Denisovan
      and Neanderthal ancestry in present-day humans and applied them to 257 high
      coverage genomes from 120 diverse populations, among which were 20 individual
      Oceanians with high Denisovan ancestry [3]. In Oceanians, the average size of
      Denisovan fragments is larger than Neanderthal fragments, implying a more recent
      average date of Denisovan admixture in the history of these populations (p =
      0.00004). We document more Denisovan ancestry in South Asia than is expected
      based on existing models of history, reflecting a previously undocumented mixture
      related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal
      ancestry, has been deleterious on a modern human genetic background, as reflected
      by its depletion near genes. Finally, the reduction of both archaic ancestries is
      especially pronounced on chromosome X and near genes more highly expressed in
      testes than other tissues (p = 1.2 * 10(-7) to 3.2 * 10(-7) for Denisovan and 2.2
      * 10(-3) to 2.9 * 10(-3) for Neanderthal ancestry even after controlling for
      differences in level of selective constraint across gene classes). This suggests
      that reduced male fertility may be a general feature of mixtures of human
      populations diverged by >500,000 years.

PMID- 27032492
TI  - Epidemiology of hepatitis B and hepatitis C in Lebanon.
AB  - BACKGROUND AND STUDY AIMS: Hepatitis B and C are two potentially life threatening
      liver infections. Lebanon is ranked as a zone of moderate endemicity. This study
      aimed to determine the prevalence of hepatitis B and C in Lebanon and their
      distribution according to age, region and sex. PATIENTS AND METHODS: This
      national prospective cross-sectional study was conducted from January 2011 till
      December 2012 in the six Lebanese Governorates in collaboration with
      municipalities, the Ministry of Public Health, Health Centres and dispensaries.
      An upcoming screening for hepatitis B and C was announced? in different districts
      of each Governorate. All individuals presenting to local laboratory, not known to
      have chronic hepatitis, were asked for a blood sample and answered a
      questionnaire addressing sex, age, place of birth and residence. Screening tests
      were "Abbots" for hepatitis B and "Human Hexagon" for hepatitis C. PCR testing
      was used to confirm the positivity of the previous tests. RESULTS: Of 31147
      individuals screened, 542 had a rapid test positive for HBV (prevalence 1.74%,
      95% CI 1.6-1.89) with a male to female ratio of 1.08. This prevalence was higher
      in the South and Nabatieh (1.9%) compared to Beirut (0.73%). Of 31,147
      individuals screened, 64 had a rapid test positive for HCV (prevalence 0.21%, 95%
      CI 0.16-0.27) with a male to female ratio of 0.85. This prevalence was higher in
      Nabatieh (0.61%) compared to Mount Lebanon (0.08%). CONCLUSIONS: The prevalence
      of HBV and HCV in Lebanon is 1.74% and 0.21%, respectively with a higher
      prevalence in South and Nabatieh districts. These data rank Lebanon amongst
      countries with low endemicity for both viruses. Decrease in the prevalence of HBV
      is due to awareness campaign as well as success of the MOPH National Hepatitis
      Program in vaccinating all new born since 1998 and in screening and vaccinating
      high risk groups.

PMID- 27032493
TI  - Prevalence of inflammatory bowel disease among patients with primary sclerosing
      cholangitis in Iran.
AB  - BACKGROUND AND STUDY AIMS: In Iran, the epidemiology of primary sclerosing
      cholangitis (PSC) and its association with inflammatory bowel disease (IBD) have
      not been studied thoroughly. This study investigates the epidemiology and
      prevalence of IBD among patients with PSC. PATIENTS AND METHODS: A retrospective
      study of 154 patients with PSC was conducted. The demographic and clinical data
      were collected, and the variables were analysed in the following two patient
      groups: patients with both PSC and IBD, and patients with PSC and without IBD.
      RESULTS: A total of 154 patients with a mean age of 40.3years (range 20-81years)
      were included, of whom 57 (37%) were female and 97 (63%) male. Ninety-six
      patients (62.3%) were diagnosed with IBD, 92 (59.7%) with ulcerative colitis, and
      four (2.6%) with Crohn's disease. In this study, elevated alkaline phosphatase
      levels were found in 90.8% of patients. The intra-hepatic duct (IHD) and
      extrahepatic duct (EHD) were involved in 70.5% of patients, isolated intrahepatic
      bile duct in 24.4%, and isolated extrahepatic duct in 3.8%. Small-duct PSC
      (normal results of imaging and PSC proved by histology of liver biopsy) was
      observed only in 1.3% of patients. CONCLUSION: PSC has become increasingly
      diagnosed in Iran. This is possibly because of better diagnostics and the
      increasing prevalence of IBD in this country. For diagnosing PSC and identifying
      the presence of IHD strictures, the results of both magnetic resonance
      cholangiopancreatography (MRCP) and endoscopic retrograde
      cholangiopancreatography (ERCP) showed good interobserver agreement, but the ERCP
      results could be used to evaluate the presence and severity of EHD strictures.

PMID- 27032495
TI  - Norisoboldine, an isoquinoline alkaloid, acts as an aryl hydrocarbon receptor
      ligand to induce intestinal Treg cells and thereby attenuate arthritis.
AB  - OBJECTIVE: Norisoboldine (NOR), an isoquinoline alkaloid with very poor oral
      bioavailability, was previously proven to have a unique anti-arthritis activity
      in rats by inducing intestinal Treg cells. Herein, we explored its underlying
      mechanism in view of aryl hydrocarbon receptor (AhR). METHODS: The
      differentiation of regulatory T cells (Treg cells) and IL-17-producing T cells
      (Th17 cells) from naive T cells was analyzed in vitro. The key role of AhR was
      ascertained using siRNA transfection. AhR agonistic effect was verified based on
      the activation of downstream signaling pathway and target genes. The correlation
      between AhR activation and Treg cell induction as well as pathological changes of
      joints was confirmed in collagen-induced arthritis (CIA) mouse model. RESULTS:
      NOR promoted intestinal Treg cell differentiation and function in an AhR
      dependent manner. It acted as an AhR agonist, as evidenced by induction of CYP1A1
      expression and activity, promotion of AhR/Hsp90 dissociation and AhR nuclear
      translocation, induction of XRE reporter activity, and facilitation of AhR/XRE
      binding. In CIA mice, NOR exerted substantial anti-arthritic effect through
      enhancing AhR activation in intestinal tissues and inducing intestinal Treg cell
      generation, which could be largely abolished by resveratrol (a antagonist of
      AhR). An adoptive transfer of Treg cells from NOR-treated mice could successfully
      alleviate arthritis symptoms in CIA mice. CONCLUSION: Oral NOR induces the
      generation of intestinal Treg cells by the activation of AhR, and thereby exerts
      anti-arthritic effect.

PMID- 27032494
TI  - Dissecting lipid metabolism in meibomian glands of humans and mice: An
      integrative study reveals a network of metabolic reactions not duplicated in
      other tissues.
AB  - Lipids comprise the bulk of the meibomian gland secretion (meibum) which is
      produced by meibocytes. Complex arrays of lipogenic reactions in meibomian
      glands, which we collectively call meibogenesis, have not been explored on a
      molecular level yet. Our goals were to elucidate the possible biosynthetic
      pathways that underlie the generation of meibum, reveal similarities in, and
      differences between, lipid metabolism in meibomian glands and other organs and
      tissues, and integrate meibomian gland studies into the field of general
      metabolomics. Specifically, we have conducted detailed analyses of human and
      mouse specimens using genomic, immunohistochemical, and lipidomic approaches.
      Among equally highly expressed genes found in meibomian glands of both species
      were those related to fatty acid elongation, branching, desaturation,
      esterification, reduction of fatty acids to alcohols, and cholesterol
      biosynthesis. Importantly, corresponding lipid products were detected in meibum
      of both species using lipidomic approaches. For the first time, a cohesive,
      unifying biosynthetic scheme that connects genomic, lipidomic, and
      immunohistochemical observations is outlined and discussed. 

PMID- 27032496
TI  - CpG DNA facilitate the inactivated transmissible gastroenteritis virus in
      enhancing the local and systemic immune response of pigs via oral administration.
AB  - Transmissible gastroenteritis virus (TGEV) replicates in the small intestine and
      induces enteritis and watery diarrhea. Establishment of local immunity in the
      intestine would thus prevent TGEV transmission. CpG DNA has been reported as a
      promising mucosal adjuvant in some animals. The effects of oral immunization of
      CpG DNA together with inactivated TGEV (ITGEV) were investigated in this study.
      Pigs (6 weeks old) were orally immunized with ITGEV plus CpG DNA. The TGEV
      specific IgA level in the intestinal tract and the TGEV-specific IgG level in
      serum significantly increased following immunization with ITGEV plus CpG DNA (P
      <= 0.05). Moreover, populations of IgA-secreting cells, CD3+ T lymphocytes and
      intraepithelial lymphocytes (IELs), in the intestine increased significantly
      after immunization with ITGEV plus CpG DNA (P <= 0.05). Furthermore, the
      expression of IL-6, IL-12 and interferon-gamma (IFN-gamma) in ligated intestine
      segments increased significantly after injection with ITGEV plus CpG DNA (P <=
      0.05). Taken together, these data suggest that oral immunization of ITGEV plus
      CpG DNA elicits a local immune response. Further studies are required to
      determine whether this immunity provides protection against TGEV in pigs.

PMID- 27032497
TI  - Innate immune responses of young bulls to a novel environment.
AB  - Animal welfare during transportation has been investigated in several studies, as
      opposed to post-transportation phases. In this study, we evaluated the effect of
      a novel environment after transportation on 26 Friesian bulls, 242 +/- 42 day
      old, from ten different dairy farms. Animals were shipped to a breeding center in
      different seasons, and selected parameters of innate immunity (serum bactericidal
      activity, hemolytic complement, serum albumin, alpha, beta, and gamma-globulins,
      interleukin-6, TNF-alpha) were monitored before and after the arrival at days-
      4/0/4/15/30. Our results showed significant differences of IL-6 and TNF-alpha
      protein levels at destination in December (94 +/- 1.3 pg/ml) and June (+788
      pg/ml), respectively. Moreover, the serum levels of these cytokines increased
      between days 0 and 15 after the arrival, the modulation of IL-6 being in
      agreement with established models of physical and/or psychological stress.
      Concerning the modulation of albumin, alpha and beta-globulins, the highest
      levels were detected in April, whereas a significant decrease was observed
      between day 15 and 30 after arrival; on the contrary, gamma-globulin levels
      significantly increased after day 15. The results of this study highlight the
      occurrence of innate immune responses of young bulls to the combined effects of
      climate (season) and novel farming conditions.

PMID- 27032498
TI  - A preventive immunization approach against insect bite hypersensitivity:
      Intralymphatic injection with recombinant allergens in Alum or Alum and
      monophosphoryl lipid A.
AB  - Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused
      by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland
      and exported to Culicoides-rich areas are frequently affected with IBH. The aims
      of the study were to compare immunization with recombinant allergens using the
      adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A
      (MPLA) for development of a preventive immunization against IBH. Twelve healthy
      Icelandic horses were vaccinated intralymphatically three times with 10 MUg each
      of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA.
      Injection with allergens in both Alum and Alum/MPLA resulted in significant
      increase in specific IgG subclasses and IgA against all r-allergens with no
      significant differences between the adjuvant groups. The induced antibodies from
      both groups could block binding of allergen specific IgE from IBH affected horses
      to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated
      PBMC from Alum/MPLA horses but not from Alum only horses produced significantly
      more IFNgamma and IL-10 than PBMC from non-vaccinated control horses. In
      conclusion, intralymphatic administration of small amounts of pure allergens in
      Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a
      promising approach for immunoprophylaxis and immunotherapy against IBH.

PMID- 27032499
TI  - Oral administration of heat-inactivated Mycobacterium bovis reduces the response
      of farmed red deer to avian and bovine tuberculin.
AB  - Orally delivered mycobacterial antigens may not sensitize the immunized animals
      causing a positive tuberculin skin test response. As the first step to address
      this critical issue, we characterized the response of farmed red deer (Cervus
      elaphus) to orally delivered heat-inactivated Mycobacterium bovis. Thirty-two
      adult red deer hinds from a farm known to be free of tuberculosis (TB) were
      randomly assigned to two different treatment groups, immunized (n=24) and control
      (n=8). Immunized hinds were dosed orally with 2 ml of PBS containing 6 * 10(6)
      heat-inactivated M. bovis. The mean skin test response of immunized deer to both
      avian purified protein derivative (aPPD) and bovine PPD (bPPD) was consistently
      lower in immunized than in control hinds. One year after immunization, immunized
      hinds had a significant reduction in the skin test response to aPPD and in the
      ELISA antibody levels against both aPPD and bPPD (24-36% reduction; P<0.05). By
      contrast, no significant change was observed in the skin test response to
      phytohaemagglutinin, or in the ELISA antibody levels against the M. bovis
      specific antigen MPB70. The mRNA levels for C3, IFN-gamma and IL-1beta and serum
      protein levels for IFN-gamma and IL-1beta did not vary between immunized and
      control deer. However, serum C3 protein levels were significantly higher
      (P=0.001) in immunized than in control deer six months after immunization. These
      results confirm that oral heat-inactivated M. bovis does not sensitize farmed red
      deer and therefore does not cause false-positive responses in the tuberculin skin
      test. The absence of sensitization in orally immunized deer opens the possibility
      of testing the vaccine in deer and possibly other ruminants without the risk of
      causing false-positive reactions in TB-tests. This study also provided the first
      evidence that orally-delivered inactivated mycobacterial antigens elicit some
      kind of immune response in a ruminant.

PMID- 27032500
TI  - Tracing the evolutionary lineage of pattern recognition receptor homologues in
      vertebrates: An insight into reptilian immunity via de novo sequencing of the
      wall lizard splenic transcriptome.
AB  - Reptiles remain a deprived class in the area of genomic and molecular resources
      for the vertebrate classes. The transition of squamates from aquatic to
      terrestrial mode of life caused profound changes in their immune system to combat
      the altered variety of pathogens on land. The current study aims at delineating
      the evolution of defence mechanisms in wall lizard, Hemidactylus flaviviridis, by
      exploring its immunome. De novo sequencing of splenic transcriptome from wall
      lizard on the Illumina Hi-Seq platform generated 258,128 unique transcripts with
      an average GC content of 45%. Annotation of 555,557 and 6812 transcripts was
      carried out against NCBI (non-redundant database) and UniProt databases,
      respectively. The KEGG pathway annotation of transcripts classified them into 39
      processes of six pathway function categories. A total of 3824 transcripts,
      involved in 23 immune-related pathways, were identified in the immune-relevant
      cluster built by harvesting the genes under KEGG pathways of immune system and
      immune diseases. Forty-two percent of the immune-relevant cluster was represented
      by pattern-recognition receptors (PRRs), of which the maximum number of
      transcripts was attributed to the Toll-like receptor (TLR) signalling pathway.
      Nine PRRs with potential full-length coding sequences were sorted for
      phylogenetic analysis and comparative domain analysis across the vertebrate
      lineage. They included DEC205/lymphocyte antigen 75 (ly75), nucleotide-binding
      oligomerisation domain-containing protein 1 (NOD1), NOD-like receptor family CARD
      domain-containing 3 (NLRC3), nucleotide-binding oligomerisation domain, leucine
      rich repeat-containing X1 (NLRX1), DDX58/retinoic acid-inducible gene 1 (RIG-1),
      Toll-like receptor 3 (TLR3), TLR4, TLR5 and TLR7. From selection studies of these
      genes, we inferred positive selection for ly75, NOD1, RIG-1, TLR3 and TLR4. Apart
      from contributing to the scarce genomic resources available for reptiles and
      giving a broad scope for the immune-relevant pathways operative in wall lizards,
      this study will also pave way for evolutionary studies on comparative immunomics.

PMID- 27032501
TI  - Identification of a suitable internal control for fluorescence analysis on canine
      peripheral blood samples.
AB  - Reliable detection of fluorescence intensity (FI) by flow cytometry (FC) is
      fundamental. FI depends on instrument settings and sample processing procedures:
      thus, measurements should be done using internal controls with known FI.
      Commercially available beads-based standards are expensive, thus reducing their
      usability in the veterinary practice. Cell subsets with stable mean FI (MFI)
      within the population have been proposed as acceptable surrogates in human
      medicine. In veterinary medicine, no data exist about stability of antigen
      expression among different subjects or upon sample storage. The aim of the
      present study was to evaluate MFI variability of main lymphocytes antigens among
      the lymphoid cells within each subject, among different subjects, and upon 24-h
      storage, in order to identify the antigen most suitable as stable internal
      control in MFI analyses. Peripheral blood samples from 18 healthy dogs were
      analysed by FC within 3h from sampling to assess the expression of CD3, CD5, CD4,
      CD8, CD21 and cyCD79b using conjugated monoclonal antibodies. Analyses were
      restricted to the lymphoid population. Fluorescent microbeads were added to each
      tube, and antigen MFI was calculated as Relative Fluorescence Intensity RFI
      (CD/beads). Fluorescence histogram CV (fhCV) for each CD was regarded as an index
      of the variability of expression among lymphocytes within each subject (cell-to
      cell variability); whereas the CV of RFI was regarded as an index of inter
      subjects variability (dog-to-dog variability). In 11 cases, FC analyses were
      repeated after 24h storage at 4 degrees C and RFI and CVs of fresh and stored
      samples were compared to assess variability linked to storage. CD4 was identified
      as the best antigen to be used as an internal control for MFI analyses in canine
      peripheral blood samples because of low cell-to-cell and dog-to-dog variability,
      and optimal stability upon 24-h storage. Blood samples from a second group of 21
      healthy dogs were labelled only with CD4, in order to assess the influence of
      breed, sex and age on the expression of CD4 in a larger case series. Based on
      univariate GLMs, none of these variables influenced CD4 RFI. Normalizing
      fluorescence data using lymphoid CD4 MFI as a reference would improve the
      comparison of results obtained by different laboratories, patients or times in
      diagnostic and research analyses of FI. Further studies are needed to confirm our
      results with different FC approaches. 

PMID- 27032502
TI  - Efficacy of commercial genotype 1 porcine reproductive and respiratory syndrome
      virus (PRRSV) vaccine against field isolate of genotype 2 PRRSV.
AB  - Although several recent studies have found that type 1 porcine reproductive and
      respiratory syndrome virus (PRRSV) modified live virus (MLV) vaccine showed
      appreciable levels of cross-protection against type 2 PRRSV infection, the
      possibility of cross-protection between two genotype of PRRSV is still
      controversial. To determine potential protective efficacy against hetero-genotype
      field strain of PRRSV and to improve understandings of the mechanisms underlying
      performance improvement after infection in vaccinated animals, piglets were
      vaccinated with type 1 PRRSV MLV vaccine and challenged with type 2 field strain
      of PRRSV. As a result, vaccinated animals gained on average 8.45 kg in comparison
      to 4.77 kg measured in non-vaccinated animals during a 3-week period after viral
      challenge, which shows using a certain PRRSV vaccine could be clinically
      effective against heterologous genotypic virus challenge. In vaccinated animals,
      viremia was reduced and cleared rapidly, whilst viral load was much higher and
      reduced more slowly, indicating rebound viremia in non-vaccinated animals. The
      titers of neutralizing antibody against the type 2 PRRSV did not exceed the
      protective level in any animal from both vaccinated and control groups. Instead,
      antibody avidity of vaccinated animals was much higher than in the control group
      clearly. Furthermore, a strong negative correlation between antibody avidity and
      viremia was noted in 80% of vaccinated animals. Through those results from tests
      evaluating degree of antibody maturation and its relevance with clearing viremia,
      it could be suggested that non-neutralizing antibodies induced by vaccination
      prior to challenge might play a key role in protection against PRRSV infection,
      especially in early time course.

PMID- 27032503
TI  - Development of single dilution immunoassay to detect E2 protein specific
      classical swine fever virus antibody.
AB  - Classical swine fever virus (CSFV) is the causative agent of a highly contagious
      disease in swine. The disease is endemic in different parts of the world and
      vaccination is the only way to protect pigs from CSFV infection. The virus
      surface protein E2 is the major immunogenic protein eliciting protective immunity
      against CSFV infection in swine. The whole virus antigen cannot differentiate
      CSFV from other pestiviruses as it cross reacts with border disease and bovine
      viral diarrhoea viruses. Commercial available ELISA is based on the whole CSFV
      particle and can lead to false positive results. Moreover, the available
      commercial ELISA is not cost effective. In the present study, a recombinant E2
      protein based single serum dilution ELISA was developed which showed enhanced
      sensitivity, specificity and accuracy as compared to commercial CSFV detection
      ELISA. The recombinant E2 protein based ELISA could be an alternate to existing
      diagnostics against CSFV infection in pigs. 

PMID- 27032504
TI  - Protective effects of Lactobacillus plantarum on epithelial barrier disruption
      caused by enterotoxigenic Escherichia coli in intestinal porcine epithelial
      cells.
AB  - Tight junctions (TJs) play an important role in maintaining the mucosal barrier
      function and gastrointestinal health of animals. Lactobacillus plantarum (L.
      plantarum) was reported to protect the intestinal barrier function of early
      weaned piglets against enterotoxigenic Escherichia coli (ETEC) K88 challenge;
      however, the underlying cellular mechanism of this protection was unclear. Here,
      an established intestinal porcine epithelia cell (IPEC-J2) model was used to
      investigate the protective effects and related mechanisms of L. plantarum on
      epithelial barrier damages induced by ETEC K88. Epithelial permeability,
      expression of inflammatory cytokines, and abundance of TJ proteins, were
      determined. Pre-treatment with L. plantarum for 6h prevented the reduction in
      transepithelial electrical resistance (TEER) (P<0.05), inhibited the increased
      transcript abundances of interleukin-8 (IL-8) and tumor necrosis factor (TNF
      alpha) (P<0.05), decreased expression of claudin-1, occludin and zonula occludens
      (ZO-1) (P<0.05) and protein expression of occludin (P<0.05) of IPEC-J2 cells
      caused by ETEC K88. Moreover, the mRNA expression of negative regulators of toll
      like receptors (TLRs) [single Ig Il-1-related receptor (SIGIRR), B-cell
      CLL/lymphoma 3 (Bcl3), and mitogen-activated protein kinase phosphatase-1 (MKP
      1)] in IPEC-J2 cells pre-treated with L. plantarum were higher (P<0.05) compared
      with those in cells just exposed to K88. Furthermore, L. plantarum was shown to
      regulate proteins of nuclear factor kappaB (NF-kappaB) and mitogen-activated
      protein kinase (MAPK) signaling pathways. These results indicated that L.
      plantarum may improve epithelial barrier function by maintenance of TEER,
      inhibiting the reduction of TJ proteins, and reducing the expression of
      proinflammatory cytokines induced by ETEC K88, possibly through modulation of
      TLRs, NF-kappaB and MAPK pathways. 

PMID- 27032506
TI  - Portfolios and 'the competent clinician': past, present and future assessment.

PMID- 27032505
TI  - Low-dose oral interferon modulates expression of inflammatory and autoimmune
      genes in cattle.
AB  - While the safety and efficacy profiles of orally administered bovine interferon
      (IFN) alpha have been documented, the mechanism(s) that result in clinical
      benefits remain elusive. One approach to delineating the molecular pathways of
      IFN efficacy is through the use of gene expression profiling technologies. In
      this proof-of-concept study, different (0, 50, 200 and 800 units) oral doses of
      natural bovine IFN (type I) were tested in cattle to determine if oral IFN
      altered the expression of genes that may be pivotal to the development of
      systemic resistance to viral infections such as foot-and-mouth disease (FMD).
      Oral IFN was administered twice: Time 0 and 8h later. Blood was collected at 0, 8
      and 24h after the first IFN administration, and DNA isolated from peripheral
      blood mononuclear cells (PBMCs) was employed in quantitative polymerase chain
      reaction (qPCR) microarray assays. Within 8h, 50 and 200 units of oral IFN
      induced significant (P<0.05) changes in expression of 41 of 92 tested autoimmune
      and inflammatory response-associated genes. These data suggest that orally
      administered IFN is a viable approach for providing short-term antiviral immunity
      to livestock exposed to viruses such as FMD virus (FMDV) until such a time that
      an effective vaccine can be produced and distributed to producers. 

PMID- 27032507
TI  - X chromosome abnormal inactivation: a unique factor for women's diseases?

PMID- 27032508
TI  - Matching phosphate and maleate buffer systems for dissolution of weak acids:
      Equivalence in terms of buffer capacity of bulk solution or surface pH?
AB  - The development of in vitro dissolution tests able to anticipate the in vivo fate
      of drug products has challenged pharmaceutical scientists over time, especially
      in the case of ionizable compounds. In the seminal model proposed by Mooney et
      al. thirty-five years ago, the pH at the solid-liquid interface (pH0) was
      identified as a key parameter in predicting dissolution rate. In the current work
      it is demonstrated that the in vitro dissolution of the weak acid ibuprofen in
      maleate and phosphate buffer systems is a function of the pH0, which in turn is
      affected by properties of the drug and the medium. The reported pH0 for ibuprofen
      dissolution in bicarbonate buffer, the predominant buffer species in the human
      small intestine under fasting conditions, can be achieved by reducing the
      phosphate buffer concentration to 5.0mM or the maleate buffer concentration to
      2.2mM. Using this approach to identify the appropriate buffer/buffer capacity
      combination for in vitro experiments in FaSSIF-type media, it would be possible
      to increase the physiological relevance of this important biopharmaceutics tool.
      However, the necessity of monitoring and adjusting the bulk pH during the
      experiments carried out in 5.0mM phosphate or 2.2mM maleate buffers must also be
      taken into consideration. 

PMID- 27032509
TI  - Novel gold nanoparticles coated with somatostatin as a potential delivery system
      for targeting somatostatin receptors.
AB  - Targeting of G-protein coupled receptors (GPCRs) like somatostatin-14 (SST-14)
      could have a potential interest in delivery of anti-cancer agents to tumor cells.
      Attachment of SST to different nano-carriers e.g. polymeric nanoparticles is
      limited due to the difficulty of interaction between SST itself and those nano
      carriers. Furthermore, the instability problems associated with the final
      formulation. Attaching of SST to gold nanoparticles (AuNPs) using the positive
      and negative charge of SST and citrate-AuNPs could be considered a new technique
      to get stable non-aggregated AuNPs coated with SST. Different analyses techniques
      have been performed to proof the principle of coating between AuNPs and SST.
      Furthermore, cellular uptake studies on HCC-1806, HELA and U-87 cell lines has
      been investigated to show the ability of AuNPs coated SST to enter the cells via
      SST receptors. Dynamic light scattering (DLS) indicated a successful coating of
      SST on the MUA-AuNPs surface. Furthermore, all the performed analysis including
      DLS, SDS-PAGE and UV-VIS absorption spectra indicated a successful coating of
      AuNPs with SST. Cellular uptake studies on HCC-1806, HELA and U-87 cell lines
      showed that the number of AuNPs-SST per cell is signiflcantly higher compared to
      citrate-AuNPs when quantified using inductively coupled plasma spectroscopy.
      Moreover, the binding of AuNPs-SST to cells can be suppressed by addition of
      antagonist, indicating that the binding of AuNPs-SST to cells is due to receptor
      specific binding. In conclusion, AuNPs could be attached to SST via adsorption to
      get stable AuNPs coated SST. This new formulation has a potential to target SST
      receptors localized in many normal and tumor cells. 

PMID- 27032510
TI  - An effective addition of uterine balloon tamponade (condom-balloon) in rural
      settings.

PMID- 27032511
TI  - Psychometric properties of the Trauma and Distress Scale, TADS, in an adult
      community sample in Finland.
AB  - BACKGROUND: There is increasing evidence that a history of childhood abuse and
      neglect is not uncommon among individuals who experience mental disorder and that
      childhood trauma experiences are associated with adult psychopathology. Although
      several interview and self-report instruments for retrospective trauma assessment
      have been developed, many focus on sexual abuse (SexAb) rather than on multiple
      types of trauma or adversity. METHODS: Within the European Prediction of
      Psychosis Study, the Trauma and Distress Scale (TADS) was developed as a new self
      report assessment of multiple types of childhood trauma and distressing
      experiences. The TADS includes 43 items and, following previous measures
      including the Childhood Trauma Questionnaire, focuses on five core domains:
      emotional neglect (EmoNeg), emotional abuse (EmoAb), physical neglect (PhyNeg),
      physical abuse (PhyAb), and SexAb.This study explores the psychometric properties
      of the TADS (internal consistency and concurrent validity) in 692 participants
      drawn from the general population who completed a mailed questionnaire, including
      the TADS, a depression self-report and questions on help-seeking for mental
      health problems. Inter-method reliability was examined in a random sample of 100
      responders who were reassessed in telephone interviews. RESULTS: After minor
      revisions of PhyNeg and PhyAb, internal consistencies were good for TADS totals
      and the domain raw score sums. Intra-class coefficients for TADS total score and
      the five revised core domains were all good to excellent when compared to the
      interviewed TADS as a gold standard. In the concurrent validity analyses, the
      total TADS and its all core domains were significantly associated with depression
      and help-seeking for mental problems as proxy measures for traumatisation. In
      addition, robust cutoffs for the total TADS and its domains were calculated.
      CONCLUSIONS: Our results suggest the TADS as a valid, reliable, and clinically
      useful instrument for assessing retrospectively reported childhood
      traumatisation.

PMID- 27032512
TI  - When deception influences memory: the implication of theory of mind.
AB  - When deceiving, one should remember to whom a falsified story was previously
      told; otherwise he or she may include inconsistencies, and the deception will
      probably be discovered. Bearing this in mind, we investigated the potential
      relationship between deception and the ability to remember to whom a piece of
      information was previously told (i.e., destination memory). Forty-one adults were
      given a destination memory task in which they had to decide to whom proverbs had
      previously been told. They were also given a questionnaire about deception (e.g.,
      "I sometimes tell lies if I have to) and a cognitive theory of mind task in which
      they had to predict the behaviour of protagonists who hold a mistaken belief
      about the state of the world. Results showed a positive correlation between
      deception and destination memory (p < .001), a relationship that was further
      mediated by cognitive theory of mind ability (p < .01). Deception requires
      monitoring and inferring what targets know, suspect, and believe. This monitoring
      ability (i.e., cognitive theory of mind) results in better processing of the
      target and consequently better destination memory. By showing the involvement of
      deception and theory of mind in destination memory, our findings emphasize the
      memory variations in social and interpersonal interactions.

PMID- 27032513
TI  - Present state of the Aral Sea: diverging physical and biological characteristics
      of the residual basins.
AB  - Latest data on the hydrophysical and biological state of the residual basins of
      the Aral Sea are presented and compared. Direct, quasi-simultaneous observations
      were carried out in the central part of the Western Large Aral Sea, the northern
      extremity of the Large Aral known as Chernyshev Bay, Lake Tshchebas, and the
      Small Aral Sea in October 2014. The Large Aral Sea and Lake Tshchebas transformed
      into hyperhaline water bodies with highly special taxocene structure. The Small
      Aral Sea was a relatively diverse brackish ecosystem, which was rather similar to
      the pre-desiccation environment. The Small Aral Sea and Lake Tshchebas exhibited
      a fully-mixed vertical structure, whereas the Western Large Aral Sea was strongly
      stratified. Our data show that during desiccation, different parts of the Aral
      Sea experienced different environmental conditions, resulting in qualitative and
      quantitative differences in the physical and biological regimes among the
      different residual basins. 

PMID- 27032514
TI  - Membrane bound Indian clade C HIV-1 envelope antigen induces antibodies to
      diverse and conserved epitopes upon DNA prime/protein boost in rabbits.
AB  - The partial success of RV144 human clinical trial demonstrated that ALVAC
      prime/envelope protein boost vaccine regimen may represent a promising strategy
      for the development of an effective HIV-1 vaccine. Our earlier study demonstrated
      that a trimeric HIV-1 envelope gp145 from an Indian clade C isolate elicited
      cross clade neutralizing antibodies primarily towards Tier 1 isolates. In the
      present study, we examined the immunogenicity of DNA prime/envelope protein boost
      vaccine in rabbits using gp160 DNA of the Indian clade C isolate with various
      cytoplasmic tail truncations and trimeric gp145 protein. Cytoplasmic tail mutants
      of gp160 exposed epitopes that reacted strongly with a number of broadly
      neutralizing human monoclonal antibodies against HIV-1. Overall, envelope
      specific titers were found to be similar in all rabbit groups with higher
      pseudovirus neutralization in protein only immunized rabbits. The complete linear
      epitope mapping of rabbit immune sera revealed strong binding to C1, C2, V3, C3
      and C4 domains of gp145. Importantly, reactivity of gp41 ecto-domain peptides was
      observed in DNA prime/protein boost sera but not in the sera of rabbits immunized
      with protein alone. Moreover, membrane anchored but not soluble envelope encoding
      DNA immunization elicited antibodies against linear epitopes on the conserved
      gp41 ecto-domain. Together, these results suggest that priming with DNA encoding
      cytoplasmic domains of Env alters the quality of antibodies elicited following
      protein boost and hence may be utilized to generate protective immunity by HIV-1
      vaccine.

PMID- 27032515
TI  - Status of research and development of vaccines for Streptococcus pyogenes.
AB  - Streptococcus pyogenes is an important global pathogen, causing considerable
      morbidity and mortality, especially in low and middle income countries where
      rheumatic heart disease and invasive infections are common. There is a number of
      promising vaccine candidates, most notably those based on the M protein, the key
      virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are
      considered as impeded vaccines because of a number of crucial barriers to
      development. Considerable effort is needed by key players to bring current
      vaccine candidates through phase III clinical trials and there is a clear need to
      develop a roadmap for future development of current and new candidates.

PMID- 27032516
TI  - A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja
      brasiliensis) induces specific immune responses and protects against lethal
      challenge.
AB  - Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from
      southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q.
      saponaria, which provides most of the saponins used as immunoadjuvants in
      vaccines. The immunostimulating capacities of aqueous extract (AE) and purified
      saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably
      comparable to those of a commercial saponin-based adjuvant preparation (Quil-A)
      in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and
      bovine viral diarrhea virus in mice model. Herein, the immunogenicity and
      protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its
      saponin fractions were compared with vaccines adjuvanted with either commercial
      Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of
      one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were
      quantified over time. A challenge experiment with a lethal dose of rabies virus
      was carried out with the formulations. Viral RNA detection in the brain of mice
      was performed by qPCR, and RNA copy-numbers were quantified using a standard
      curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted
      vaccines significantly enhanced levels of specific IgG isotypes when compared
      with the no adjuvant group (P <= 0.05). Overall, one or two doses of saponin
      based vaccine were efficient to protect against the lethal rabies exposure. Both
      AE and saponin fractions from Q. brasiliensis leaves proved potent immunological
      adjuvants in vaccines against a lethal challenge with a major livestock pathogen,
      hence confirming their value as competitive or complementary sustainable
      alternatives to saponins of Q. saponaria.

PMID- 27032517
TI  - Nontyphoidal salmonella disease: Current status of vaccine research and
      development.
AB  - Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica
      serovar Typhimurium and S. enterica serovar Enteritidis account for approximately
      fifty percent of all human isolates of NTS reported globally. The global
      incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases,
      approximately 80 million of which were contracted via food-borne transmission. It
      is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes
      severe, extra-intestinal, invasive bacteremia, referred to as invasive
      nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a
      febrile illness, frequently without gastrointestinal symptoms, in both adults and
      children. Symptoms of iNTS are similar to malaria, often including fever (>90%)
      and splenomegaly (>40%). The underlying reasons for the high rates of iNTS
      disease in Africa are still being elucidated. Evidence from animal and human
      studies supports the feasibility of developing a safe and effective vaccine
      against iNTS. Both antibodies and complement can kill Salmonella species in
      vitro. Proof-of-principle studies in animal models have demonstrated efficacy for
      live attenuated and subunit vaccines that target the O-antigens, flagellin
      proteins, and other outer membrane proteins of serovars Typhimurium and
      Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been
      developed: the Generalized Modules for Membrane Antigens (GMMA) technology which
      presents surface polysaccharides and outer membrane proteins in their native
      conformation. GMMA technology is self-adjuvanting, as it delivers multiple
      pathogen-associated molecular pattern molecules. GMMA may be particularly
      relevant for low- and middle-income countries as it has the potential for high
      immunologic potency at a low cost and involves a relatively simple production
      process without the need for complex conjugation. Several vaccines for the
      predominant NTS serovars Typhimurium and Enteritidis, are currently under
      development.

PMID- 27032518
TI  - Prevalence of Aneurysmal Subarachnoid Hemorrhage Safety Indicators and Their
      Relation with Health Care Outcomes in a Mexican Population.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (ASAH) is a serious and unstable
      condition. Patient safety indicators (PSI) are a group of potentially preventable
      events in patient health care. The aim of this study is to determine the
      prevalence of 8 relevant PSI in a group of patients with ASAH and their relation
      with 2 health care outcomes. METHODS: We performed a retrospective review of all
      patients admitted with ASAH. A total of 35 patients were selected with the
      following variables: age, sex, Hunt and Hess scale at admission, brain aneurysm
      treatment, length of hospital stay, and Glasgow Outcome Scale (GOS) score with
      the presence or absence of all 8 PSI: decubitus ulcer, pneumothorax, bacteremia,
      perioperative hematoma, postoperative respiratory failure, deep vein thrombosis
      (DVT), pulmonary thromboembolism, and accidental puncture or laceration. RESULTS:
      Average age (+/-standard deviation) was 53 +/- 13.9 years, with a female
      predominance of 63%. The most common PSI was decubitus ulcer followed by central
      line-related bacteremia. Prolonged hospital stay was increased for inpatients
      with DVT. Males had a risk effect (odds ratio, 6.25) in relation to the
      appearance of pulmonary thromboembolism as well as a poor neurologic condition
      according to the GOS (GOS score <4) related to the appearance of DVT (odds ratio,
      8.0). CONCLUSIONS: In our study population, we found 3 PSI related to a poor
      outcome measured with the GOS or to a longer hospital stay: decubitus ulcer,
      central line-related bacteremia, and DVT. PSI have been academically considered
      as useful tools in clinical, epidemiologic, and research outcome scenarios. An
      adequate prevention protocol for these indicators could produce better outcomes
      in medical care for patients with ASAH.

PMID- 27032519
TI  - Preoperative Volumetric Assessment Matched with High-Field Intraoperative
      Magnetic Resonance Imaging-Guided Stereotactic Evacuation of Brain Abscesses.
AB  - OBJECTIVE AND BACKGROUND: Stereotactic evacuation is currently accepted as a
      minimally invasive surgical procedure for the management of brain abscesses.
      Intraoperative magnetic resonance imaging (Io-MRI) is well established in neuro
      oncology but its role has not been completely outlined for brain abscess surgery.
      The objective of this work is to analyze radiologic, clinical, and laboratory
      results in a cohort of patients with brain abscesses treated with an original
      protocol in which the minimally invasiveness of a stereotactic technique is
      matched with preoperative volumetric evaluation and Io-MRI. METHODS: For each of
      the 12 patients included in this cohort, the following data were recorded: age,
      sex, location, presentation, grade of evacuation, duration of follow-up, mean
      preoperative and postoperative Glasgow Outcome Scale score, functional outcome,
      number of abscess loculations, number of Io-MRI, duration of antibiotic therapy,
      preoperative and postoperative laboratory findings, pathogen strains and possible
      recurrences. RESULTS: The operative time was in 10/12 patients under 90 minutes.
      A total of 8/12 patients needed no more than 30 days of antibiotics; 9/12
      patients had minor or no sequelae and returned to normal activities; only 1
      recurrence of brain abscess was recorded in the sample. Only 1 death was recorded
      in the sample. CONCLUSIONS: Although this work is intended to present preliminary
      results of an original protocol for the management of brain abscess, the role of
      a precise preoperative volumetric evaluation matched with Io-MRI in the treatment
      of this disease seems of great benefit, as in surgical neuro-oncology.

PMID- 27032520
TI  - Complications of Epilepsy Surgery: A Single Surgeon's Experience from South
      India.
AB  - OBJECTIVE: Epilepsy surgery is largely underused in developing counties as a
      result of many misconceptions. The current study evaluates complications of
      epilepsy surgery performed by a single surgeon from South India. METHODS: A
      retrospective analysis was performed of 697 consecutive patients who underwent
      epilepsy surgery. Complications were classified as minor and major medical,
      neurologic, and psychiatric complications. The study population was divided into
      groups of surgery for temporal lobe epilepsy (TLE), extratemporal lobe epilepsy
      (ETLE), and other procedures. Incidence of complications was compared in children
      aged <=12 years and those aged >12 years. Engel class I and IIA was classified as
      favorable outcomes. RESULTS: The average age of the cohort was 21.9 +/- 11.15
      years, with 300 (42.8%) females. The mortality was 0.14%. Medical complications
      were observed in 2%: minor in 10 patients (1.43%) and major in 4 patients
      (0.57%). In patients with TLE (n = 467), minor and major neurologic complications
      were observed in 18 patients (3.9%) and 4 patients (0.9%), respectively, and 14
      patients (2.9%) had psychiatric complications. In 175 patients with ETLE, the
      lesion was in noneloquent area in 108; no patients had major and 20 patients
      (18.5%) had minor neurologic complications. In the remaining 67 patients with
      ETLE with eloquent area surgery, 29 patients (43.2%) had neurologic deficits as
      expected, and 12 (17.9%) had major neurologic deficit. Age did not influence
      complications. Engel favorable outcome was reported in 400 patients with TLE
      (85.7%) and 116 patients with ETLE (65.2%). CONCLUSIONS: In the current study,
      risk of mortality was 0.1% and rate of overall major complications was 1.4%.
      Epilepsy surgery should be increasingly used in developing countries.

PMID- 27032521
TI  - Tranexamic Acid for Treatment of Residual Subdural Hematoma After Bedside Twist
      Drill Evacuation.
AB  - BACKGROUND: Management of nonemergent, nonacute subdural hematomas (SDHs) ranges
      from observation to burr-hole evacuation or craniotomy, but recurrence rates are
      high. We evaluated the safety and efficacy of tranexamic acid (TXA) for the
      treatment of residual SDHs after bedside twist-drill evacuation. METHODS: We
      performed a retrospective analysis of a prospectively maintained database from
      November 2013 to November 2014 for all patients who underwent placement of a
      bedside subdural evacuating port system (SEPS) followed by treatment with oral
      TXA (650 mg daily). All demographics, evidence of venous thromboembolism, and
      volumes of pertinent computed tomography were obtained. RESULTS: Twenty subdural
      hematomas in 14 patients met the inclusion criteria for this study. Most SDHs
      were mixed density. Mean SDH volume on presentation was 145.96 +/- 40.22 cm(3)
      with a mean midline shift of 9.44 +/- 4.84 mm. Mean volumes decreased to 80.00 +/
      31.96 cm(3) and midline shift improved to 4.44 +/- 3.29 mm after SEPS placement
      (P < 0.0001 and P = 0.0046). All patients were placed on TXA after their
      procedure. Mean follow-up with computed tomography was 92.1 +/- 27.5 days, and
      mean SDH volume at last follow-up was 7.41 +/- 15.54 cm(3) with a mean midline
      shift of 0.19 +/- 0.69 mm (P < 0.0001 and P = 0.0002). Percent volume reduction
      was significantly higher after TXA than after SEPS (91.31% vs. 40.74%; P <
      0.0001). No increase or delayed recurrence of the SDH was noted during TXA
      treatment. All but 1 clinical presenting symptom improved at follow-up. No venous
      thromboembolisms were noted among the patients. CONCLUSIONS: In our pilot study,
      chronic SDH volumes were reduced by 40.74% after SEPS drainage. The residual
      volume was reduced by an additional 91.31% during oral TXA treatment. No patients
      developed delayed recurrence or expansion of their SDHs. Further prospective
      studies are needed to evaluate the role of TXA for adjunctive treatment of
      chronic SDHs.

PMID- 27032522
TI  - Ultrasonic Observation and Clinical Application of Arcade of Struthers in the Mid
      Arm.
AB  - BACKGROUND: The mid-arm structure named arcade of Struthers has been shrouded in
      controversy since it was identified. Most specimens in previous studies were
      European. The occurrence, component, extent, and position of this structure in
      the xanthoderm are not clear. Moreover, research into the arcade of Struthers has
      been at the anatomic level and there has been no ultrasonic research. The aim of
      this study was to elucidate and measure this anatomy by both anatomic dissection
      and ultrasonic observation to provide clear and definite criteria to classify the
      arcade of Struthers, as well as operation guidelines for identifying the arcade
      of Struthers in ultrasonic imaging and surgical decompression. METHODS: Sixty
      four upper limb specimens of 32 adult cadavers were dissected. The tendinous
      arcade of Struthers (TAS) and muscular arcade of Struthers (MAS) were observed
      and measured, as well as the position at which the medial intermuscular septum
      was pierced by the ulnar nerve. The position at which the concomitant blood
      vessel began to accompany the ulnar nerve was also recorded. Twenty healthy adult
      participants were enrolled for ultrasonic research. The ulnar nerve was scanned
      from the cubital tunnel to the fossa axillaris for the anatomic structure
      crossing it. Once the arcade of Struthers was found, the distal and proximal
      limits were marked on the skin and it was then measured. RESULTS: Anatomic study
      showed TASs in 21 limbs, and MASs were found in 16 limbs. The total incidence of
      the arcade of Struthers was 57.8%. The length of TAS (2.12 +/- 0.62 cm) and MAS
      (4.46 +/- 1.96 cm) had a significant difference and the distance between its
      proximal limit and the medial humeral epicondyle were 8.93 +/- 1.38 cm and 9.50
      +/- 1.69 cm, respectively. Ultrasonic study showed that the incidence of the
      arcade of Struthers was 50.0%. The distance between its proximal limit and the
      medial humeral epicondyle was 8.52 +/- 1.88 cm and 9.45 +/- 1.76 cm. The length
      was 1.85 +/- 1.8 cm and 4.23 +/- 1.93 cm, respectively. CONCLUSIONS: We believed
      that an arcade of Struthers described by multiple investigators did exist in
      Chinese people, and based on our study, it was classified into 2 types: TAS and
      MAS. Caution should be used to preserve the superior ulnar collateral artery when
      incising the arcade of Struthers. Ultrasonography can detect the existence ratio,
      dimension, and location of the arcade of Struthers.

PMID- 27032523
TI  - Pediatric Head Injury: A Global Tragedy and a Public Policy Challenge.

PMID- 27032524
TI  - Short Segment Stabilization by Protecting the Alar Ligaments in a Case of
      Eosinophilic Granuloma Involving the C2 Spine.
AB  - BACKGROUND: The craniocervical junction is a complex anatomic location that
      contains the occipital bone, atlas, axis, and important complex ligamentous
      structures. The stability of this region is ensured only with the help of
      ligaments. CASE DESCRIPTION: A 6-year-old boy was admitted to our clinic for neck
      pain. Computed tomography and magnetic resonance imaging revealed a lytic bone
      lesion involving the C2 vertebral body and pedicle without odontoid tip. The
      tumor was resected using an anterior retropharyngeal approach and a wide marginal
      resection method. The odontoid tip and alar ligaments were protected, and the
      costal autografts were located between the C1-odontoid tip and the C3 body. The
      costal graft was stabilized in the C3 body with a miniplate. Then, C1-C3
      posterior fixation with fusion was performed. The craniocervical junction was not
      considered unstable because the occipital bone was not involved in the fusion.
      Histologic examination confirmed the diagnosis of eosinophilic granuloma. Fusion
      was detected on a 1-year postoperative cervical computed tomography scan.
      CONCLUSIONS: The occiput should not be involved in the fusion area when the alar
      ligaments are preserved during surgery for a C2 lesion.

PMID- 27032525
TI  - The Autoclaving of Autologous Bone is a Risk Factor for Surgical Site Infection
      After Cranioplasty.
AB  - BACKGROUND: This retrospective study was designed to evaluate the effectiveness
      of autoclaving for the prevention of surgical site infection (SSI) after
      cranioplasty. METHODS: Patients who underwent cranioplasty with autologous bone
      were enrolled. SSI was defined as an infection requiring bone flap removal. Risk
      factors of SSI, as reported by other researchers, and microbiologic features of
      SSI were analyzed. All bone flaps were preserved in a deep freezer (-70 degrees
      C). Autoclaving of the preserved autologous bone flap before cranioplasty was
      performed for 5 minutes at 135 degrees C in the 26 patients. RESULTS: Eighty
      patients were enrolled. The mean age was 53.3 years and the male/female ratio was
      3:2. Causes of craniectomy included trauma (n = 37) and nontrauma (n = 43). The
      mean time interval between craniectomy and cranioplasty was 49.7 days. The SSI
      rate after cranioplasty with autologous bone was 17.5% (n = 14). In univariate
      analysis, the cranioplasty operation time (P = 0.09) and the use of autoclaved
      bone (P = 0.00) were supposed to be risk factors for SSI. The use of autoclaved
      autologous bone was found to be the only risk factor of SSI (P = 0.01; hazard
      ratio = 8.88) in binary logistic regression analysis. Non-methicillin-resistant
      Staphylococcus aureus (MRSA) causes were more frequent in the autoclaved group
      (MRSA, 30%; non-MRSA, 70%) compared with the nonautoclaved group (MRSA, 100%) (P
      = 0.07). A microscopic examination showed that autoclaving after long-term
      cryopreservation may result in a loss of bone viability. CONCLUSIONS: Autoclaving
      of autologous bone causes SSI after cranioplasty and it seems to increase the
      risk of non-MRSA infection by normal skin flora.

PMID- 27032527
TI  - Iterative feature refinement for accurate undersampled MR image reconstruction.
AB  - Accelerating MR scan is of great significance for clinical, research and advanced
      applications, and one main effort to achieve this is the utilization of
      compressed sensing (CS) theory. Nevertheless, the existing CSMRI approaches still
      have limitations such as fine structure loss or high computational complexity.
      This paper proposes a novel iterative feature refinement (IFR) module for
      accurate MR image reconstruction from undersampled K-space data. Integrating IFR
      with CSMRI which is equipped with fixed transforms, we develop an IFR-CS method
      to restore meaningful structures and details that are originally discarded
      without introducing too much additional complexity. Specifically, the proposed
      IFR-CS is realized with three iterative steps, namely sparsity-promoting
      denoising, feature refinement and Tikhonov regularization. Experimental results
      on both simulated and in vivo MR datasets have shown that the proposed module has
      a strong capability to capture image details, and that IFR-CS is comparable and
      even superior to other state-of-the-art reconstruction approaches. 

PMID- 27032526
TI  - A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid beta
      Aggregates.
AB  - A major challenge in the Alzheimer's disease (AD) is its timely diagnosis.
      Amyloid beta (Abeta) aggregates have been proposed as the most viable biomarker
      for the diagnosis of AD. Here, we demonstrate hemicyanine-based benzothiazole
      coumarin (TC) as a potential probe for the detection of highly toxic Abeta42
      aggregates through switch-on, enhanced (~30 fold) red fluorescence (Emax = 654
      nm) and characteristic colorimetric (light red to purple) optical outputs.
      Interestingly, TC exhibits selectivity towards Abeta42 fibrils compared to other
      abnormal protein aggregates. TC probe show nanomolar binding affinity (Ka = 1.72
      * 10(7) M(-1)) towards Abeta42 aggregates and also displace ThT bound to Abeta42
      fibrils due to its high binding affinity. The Abeta42 fibril-specific red-shift
      in the absorption spectra of TC responsible for the observed colorimetric optical
      output has been attributed to micro-environment change around the probe from
      hydrophilic-like to hydrophobic-like nature. The binding site, binding energy and
      changes in optical properties observed for TC upon interaction with Abeta42
      fibrils have been further validated by molecular docking and time dependent
      density functional theory studies. 

PMID- 27032528
TI  - 2015 JOSPT Awards: Back Pain and Anterior Cruciate Ligament Injuries Are a
      Continued Focus of Research and Clinical Attention in Physical Therapy.
AB  - During the American Physical Therapy Association's Combined Sections Meeting in
      Anaheim, California in February 2016, JOSPT recognized the authors of the most
      outstanding research and clinical practice manuscripts published in JOSPT during
      the 2015 calendar year. The 2015 JOSPT Excellence in Research Award was presented
      to Bjorn Aasa, Lars Berglund, Peter Michaelson, and Ulrika Aasa for their paper
      titled "Individualized Low-Load Motor Control Exercises and Education Versus a
      High-Load Lifting Exercise and Education to Improve Activity, Pain Intensity, and
      Physical Performance in Patients With Low Back Pain: A Randomized Controlled
      Trial." The 2015 George J. Davies-James A. Gould Excellence in Clinical Inquiry
      Award was presented to Anne Benjaminse, Alli Gokeler, Bert Otten, Ariel V.
      Dowling, Avery Faigenbaum, Kevin R. Ford, Timothy E. Hewett, James A. Onate, and
      Gregory D. Myer for their work titled "Optimization of the Anterior Cruciate
      Ligament Injury Prevention Paradigm: Novel Feedback Techniques to Enhance Motor
      Learning and Reduce Injury Risk."

PMID- 27032529
TI  - Patellofemoral Osteoarthritis: Are We Missing an Important Source of Symptoms
      After Anterior Cruciate Ligament Reconstruction?
AB  - Anterior cruciate ligament (ACL) rupture is a well-established risk factor for
      knee osteoarthritis (OA). Fifty to ninety percent of individuals will develop
      radiographic tibiofemoral OA within a decade after ACL injury and anterior
      cruciate ligament reconstruction (ACLR). Although less well recognized,
      radiographic patellofemoral OA is present in approximately 50% of individuals at
      more than 10 years after ACLR. This early-onset OA and its associated pain and
      functional limitations pose a particular challenge to younger adults with OA
      compared to an older OA population. Targeted interventions need to be developed
      to reduce the burden of early-onset OA following ACLR. Emerging evidence suggests
      that such interventions should target both the patellofemoral and tibiofemoral
      joints.

PMID- 27032531
TI  - April 2016 Erratum.
AB  - Corrections to an article published in March 2016 of JOSPT: Courtney CA, Steffen
      AD, Fernandez-de-Las-Penas C, Kim J, Chmell SJ. Joint mobilization enhances
      mechanisms of conditioned pain modulation in individuals with osteoarthritis of
      the knee. J Orthop Sports Phys Ther 2016;46(3):168-176.
      doi:10.2519/jospt.2016.6259.

PMID- 27032530
TI  - Cauda Equina Compression in the Absence of Neurologic Signs.
AB  - The patient was a 45-year-old man with a 4-year history of chronic low back pain,
      intensifying insidiously over the previous 8 months. On physical examination,
      generalized, severe low back pain was increased with all motions, with no
      abnormal neurologic signs. The initial physical therapy diagnosis was nonspecific
      low back pain; however, when the patient reported worsening symptoms at 2-week
      follow-up, he was advised to complete his previously scheduled magnetic resonance
      imaging and physician follow-up before further physical therapy. Magnetic
      resonance imaging revealed a mass at L5 consistent with benign nerve sheath
      tumor.

PMID- 27032532
TI  - Effect of solution treatment on the fatigue behavior of an as-forged Mg-Zn-Y-Zr
      alloy.
AB  - Through investigating and comparing the fatigue behavior of an as-forged Mg-6.7Zn
      1.3Y-0.6Zr (wt.%) alloy before and after solid solution treatment (T4) in
      laboratory air, the effect of T4 treatment on fatigue crack initiation was
      disclosed. S-N curves illustrated that the fatigue strength of as-forged samples
      was 110 MPa, whereas the fatigue strength of T4 samples was only 80 MPa.
      Observations to fracture surfaces demonstrated that for as-forged samples,
      fatigue crack initiation sites were covered with a layer of oxide film. However,
      due to the coarse grain structure and the dissolution of MgZn2 precipitates, the
      activation and accumulation of {10-12} twins in T4 samples were much easier,
      resulting in the preferential fatigue crack initiation at cracked twin boundaries
      (TBs). Surface characterization demonstrated that TB cracking was mainly ascribed
      to the incompatible plastic deformation in the twinned area and nearby alpha-Mg
      matrix. 

PMID- 27032533
TI  - Disentangling effects of abiotic factors and biotic interactions on cross-taxon
      congruence in species turnover patterns of plants, moths and beetles.
AB  - High cross-taxon congruence in species diversity patterns is essential for the
      use of surrogate taxa in biodiversity conservation, but presence and strength of
      congruence in species turnover patterns, and the relative contributions of
      abiotic environmental factors and biotic interaction towards this congruence,
      remain poorly understood. In our study, we used variation partitioning in
      multiple regressions to quantify cross-taxon congruence in community
      dissimilarities of vascular plants, geometrid and arciinid moths and carabid
      beetles, subsequently investigating their respective underpinning by abiotic
      factors and biotic interactions. Significant cross-taxon congruence observed
      across all taxon pairs was linked to their similar responses towards elevation
      change. Changes in the vegetation composition were closely linked to carabid
      turnover, with vegetation structure and associated microclimatic conditions
      proposed causes of this link. In contrast, moth assemblages appeared to be
      dominated by generalist species whose turnover was weakly associated with
      vegetation changes. Overall, abiotic factors exerted a stronger influence on
      cross-taxon congruence across our study sites than biotic interactions. The weak
      congruence in turnover observed particularly between plants and moths highlights
      the importance of multi-taxon approaches based on groupings of taxa with similar
      turnovers, rather than the use of single surrogate taxa or environmental proxies,
      in biodiversity assessments. 

PMID- 27032534
TI  - Capillarity ion concentration polarization as spontaneous desalting mechanism.
AB  - To overcome a world-wide water shortage problem, numerous desalination methods
      have been developed with state-of-the-art power efficiency. Here we propose a
      spontaneous desalting mechanism referred to as the capillarity ion concentration
      polarization. An ion-depletion zone is spontaneously formed near a nanoporous
      material by the permselective ion transportation driven by the capillarity of the
      material, in contrast to electrokinetic ion concentration polarization which
      achieves the same ion-depletion zone by an external d.c. bias. This capillarity
      ion concentration polarization device is shown to be capable of desalting an
      ambient electrolyte more than 90% without any external electrical power sources.
      Theoretical analysis for both static and transient conditions are conducted to
      characterize this phenomenon. These results indicate that the capillarity ion
      concentration polarization system can offer unique and economical approaches for
      a power-free water purification system. 

PMID- 27032535
TI  - Irreversible electroporation of the liver: is there a safe limit to the ablation
      volume?
AB  - Irreversible electroporation is a fast-growing liver ablation technique. Although
      safety has been well documented in small ablations, our aim is to assess its
      safety and feasibility when a large portion of liver is ablated. Eighty-seven
      mice were subjected to high voltage pulses directly delivered across parallel
      plate electrodes comprising around 40% of mouse liver. One group consisted in 55
      athymic-nude, in which a tumor from the KM12C cell line was grown and the other
      thirty-two C57-Bl6 non-tumoral mice. Both groups were subsequently divided into
      subsets according to the delivered field strength (1000 V/cm, 2000 V/cm) and
      whether or not they received anti-hyperkalemia therapy. Early mortality (less
      than 24 hours post-IRE) in the 2000 V/cm group was observed and revealed
      considerably higher mean potassium levels. In contrast, the animals subjected to
      a 2000 V/cm field treated with the anti-hyperkalemia therapy had higher survival
      rates (OR = 0.1, 95%CI = 0.02-0.32, p < 0.001). Early mortality also depended on
      the electric field magnitude of the IRE protocol, as mice given 1000 V/cm
      survived longer than those given 2000 V/cm (OR = 4.7, 95%CI = 1.8-11.8, p =
      0.001). Our findings suggest that ionic disturbances, mainly due to potassium
      alterations, should be warned and envisioned when large volume ablations are
      performed by IRE. 

PMID- 27032536
TI  - Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by
      releasing PGE2.
AB  - Chemotherapies often induce drug-resistance in cancer cells and simultaneously
      stimulate proliferation and activation of Myeloid-Derived Suppressor Cells
      (MDSCs) to inhibit anti-tumor T cells, thus result in poor prognosis of patients
      with breast cancers. To date, the mechanism underlying the expansion of MDSCs in
      response to chemotherapies is poorly understood. In the present study, we used in
      vitro cell culture and in vivo animal studies to demonstrate that doxorubicin
      resistant breast cancer cells secret significantly more prostaglandin E2 (PGE2)
      than their parental doxorubicin-sensitive cells. The secreted PGE2 can stimulate
      expansion and polymerization of MDSCs by directly target to its receptors,
      EP2/EP4, on the surface of MDSCs, which consequently triggers production of miR
      10a through activating PKA signaling. More importantly, activated MDSCs can
      inhibit CD4(+)CD25(-) T cells as evidenced by reduced proliferation and IFN-gamma
      release. In order to determine the molecular pathway that involves miR-10a
      mediated activation of MDSCs, biochemical and pharmacological studies were
      carried out. We found that miR-10a can activate AMPK signaling to promote
      expansion and activation of MDSCs. Thus, these results reveal, for the first
      time, a novel role of PGE2/miR-10a/AMPK signaling axis in chemotherapy-induced
      immune resistance, which might be targeted for treatment of chemotherapy
      resistant tumors. 

PMID- 27032537
TI  - Raman spectroscopy for cytopathology of exfoliated cervical cells.
AB  - Cervical cancer is the fourth most common cancer affecting women worldwide but
      mortality can be decreased by early detection of pre-malignant lesions. The Pap
      smear test is the most commonly used method in cervical cancer screening
      programmes. Although specificity is high for this test, it is widely acknowledged
      that sensitivity can be poor mainly due to the subjective nature of the test.
      There is a need for new objective tests for the early detection of pre-malignant
      cervical lesions. Over the past two decades, Raman spectroscopy has emerged as a
      promising new technology for cancer screening and diagnosis. The aim of this
      study was to evaluate the potential of Raman spectroscopy for cervical cancer
      screening using both Cervical Intraepithelial Neoplasia (CIN) and Squamous
      Intraepithelial Lesion (SIL) classification terminology. ThinPrep(r) Pap samples
      were recruited from a cervical screening population. Raman spectra were recorded
      from single cell nuclei and subjected to multivariate statistical analysis.
      Normal and abnormal ThinPrep(r) samples were discriminated based on the
      biochemical fingerprint of the cells using Principal Component Analysis (PCA).
      Principal Component Analysis - Linear Discriminant Analysis (PCA-LDA) was
      employed to build classification models based on either CIN or SIL terminology.
      This study has shown that Raman spectroscopy can be successfully applied to the
      study of routine cervical cytology samples from a cervical screening programme
      and that the use of CIN terminology resulted in improved sensitivity for high
      grade cases.

PMID- 27032538
TI  - The importance of high quality trials of cognitive interventions in Alzheimer's
      disease.
AB  - Currently available treatments for Alzheimer's disease (AD) are disappointing and
      their modest benefits do not reflect the increased understanding of the condition
      that has arisen from the last 50 years of research or the huge investments made
      by the pharmaceutical industry and academia in developing therapies.
      Cholinesterase inhibitors and memantine are evidence-based symptomatic treatments
      that offer benefits at the margins of clinical significance, but successive
      failures in trials of putative disease-modifying drugs have led researchers to
      investigate the potential efficacy of non-drug interventions. Exercise and
      cognitive-based interventions have received the most attention, but we are still
      a long way from understanding whether any can offer real benefit to patients with
      AD (Huntley et al., 2015). 

PMID- 27032539
TI  - Design of a confined environment using protein cages and crystals for the
      development of biohybrid materials.
AB  - There is growing interest in the design of protein assemblies for use in
      materials science and bionanotechnology. Protein assemblies, such as cages and
      crystalline protein structures, provide confined chemical environments that allow
      immobilization of metal complexes, nanomaterials, and proteins by metal
      coordination, assembly/disassembly reactions, genetic manipulation and
      crystallization methods. Protein assembly composites can be used to prepare
      hybrid materials with catalytic, magnetic and optical properties for cellular
      applications due to their high stability, solubility and biocompatibility. In
      this feature article, we focus on the recent development of ferritin as the most
      promising molecular template protein cage and in vivo and in vitro engineering of
      protein crystals as solid protein materials with functional properties.

PMID- 27032540
TI  - Milk fat globule is an alternative to mammary epithelial cells for gene
      expression analysis in buffalo.
AB  - Owing to the difficulty in obtaining mammary gland tissue from lactating animals,
      it is difficult to test the expression levels of genes in mammary gland. The aim
      of the current study was to identify if milk fat globule (MFG) in buffalo milk
      was an alternative to mammary gland (MG) and milk somatic cell (MSC) for gene
      expression analysis. Six buffalos in late lactation were selected to collect MFG
      and MSC, and then MG was obtained by surgery. MFG was stained with acridine
      orange to successfully visualise RNA and several cytoplasmic crescents in MFG.
      The total RNA in MFG was successfully isolated and the integrity was assessed by
      agarose gel electrophoresis. We analysed the cellular components in MFG, MG and
      MSC through testing the expression of cell-specific genes by qRT-PCR. The results
      showed that adipocyte-specific gene (AdipoQ) and leucocyte-specific genes (CD43,
      CSF1 and IL1alpha) in MFG were not detected, whereas epithelial cell marker genes
      (Keratin 8 and Keratin 18) in MFG were higher than in MSC and lower than in MG,
      fibroblast marker gene (vimentin) in MFG was significantly lower than in MG and
      MSC, milk protein genes (LALBA, BLG and CSN2) and milk fat synthesis-related
      genes (ACC, BTN1A1, FABP3 and FAS) in MFG were higher than in MG and MSC. In
      conclusion, the total RNA in MFG mainly derives from mammary epithelial cells and
      can be used to study the functional gene expression of mammary epithelial cells. 

PMID- 27032541
TI  - Development of a Weight Loss Mobile App Linked With an Accelerometer for Use in
      the Clinic: Usability, Acceptability, and Early Testing of its Impact on the
      Patient-Doctor Relationship.
AB  - BACKGROUND: Although complications of obesity are well acknowledged and managed
      by clinicians, management of obesity itself is often difficult, which leads to
      its underdiagnosis and undertreatment in hospital settings. However, tools that
      could improve the management of obesity, including self-monitoring, engagement
      with a social network, and open channels of communication between the patient and
      doctor, are limited in a clinic-based setting. OBJECTIVE: The objective of our
      study was to evaluate the usability and acceptability of a newly developed mobile
      app linked with an accelerometer and its early effects on patient-doctor
      relationships. METHODS: From September 2013 to February 2014, we developed a
      mobile app linked with an accelerometer as a supportive tool for a clinic-based
      weight loss program. The app used information from electronic health records and
      delivered tailored educational material. Personal goal setting, as well as
      monitoring of weight changes and physical activity combined with feedback, are
      key features of the app. We also incorporated an interactive message board for
      patients and doctors. During the period of March 2014 to May 2014, we tested our
      mobile app for 1 month in participants in a hospital clinic setting. We assessed
      the app's usability and acceptability, as well as the patient-doctor
      relationship, via questionnaires and analysis of app usage data. RESULTS: We
      recruited 30 individuals (18 male and 12 female) for the study. The median number
      of log-ins per day was 1.21, with the most frequently requested item being
      setting goals, followed by track physical activities and view personal health
      status. Scales of the depth of the patient-doctor relationship decreased from
      27.6 (SD 4.8) to 25.1 (SD 4.5) by a Wilcoxon signed rank test (P=.02).
      CONCLUSIONS: A mobile phone app linked with an accelerometer for a clinic-based
      weight loss program is useful and acceptable for weight management but exhibited
      less favorable early effects on patient-doctor relationships.

PMID- 27032542
TI  - Irritable Bowel Syndrome: Is It Really a Functional Disorder? A New Perspective
      on Alteration of Enteric Nervous System.

PMID- 27032543
TI  - Dysregulated MicroRNA Expression in Irritable Bowel Syndrome.

PMID- 27032545
TI  - Esophagogastric Junction Outflow Obstruction Transformed to Type II Achalasia.

PMID- 27032546
TI  - Progression of Jackhammer Esophagus to Achalasia.

PMID- 27032544
TI  - Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could
      Play a Role in Neuropsychiatric Health and Diseases.
AB  - Gut microbiome is an integral part of the Gut-Brain axis. It is becoming
      increasingly recognized that the presence of a healthy and diverse gut microbiota
      is important to normal cognitive and emotional processing. It was known that
      altered emotional state and chronic stress can change the composition of gut
      microbiome, but it is becoming more evident that interaction between gut
      microbiome and central nervous system is bidirectional. Alteration in the
      composition of the gut microbiome can potentially lead to increased intestinal
      permeability and impair the function of the intestinal barrier. Subsequently,
      neuro-active compounds and metabolites can gain access to the areas within the
      central nervous system that regulate cognition and emotional responses.
      Deregulated inflammatory response, promoted by harmful microbiota, can activate
      the vagal system and impact neuropsychological functions. Some bacteria can
      produce peptides or short chain fatty acids that can affect gene expression and
      inflammation within the central nervous system. In this review, we summarize the
      evidence supporting the role of gut microbiota in modulating neuropsychological
      functions of the central nervous system and exploring the potential underlying
      mechanisms. 

PMID- 27032547
TI  - Progression of Jackhammer Esophagus to Achalasia: Author's Reply.

PMID- 27032548
TI  - Pharmacologic Management of Type 2 Diabetes: 2016 Interim Update.

PMID- 27032549
TI  - Learning From Heart Failure: How Will We Lead Bladder Failure Into the Future?

PMID- 27032550
TI  - Interstitial Cystitis/Bladder Pain Syndrome: A Urologic Mystery.

PMID- 27032551
TI  - Rescue of Heart Failure by Mitochondrial Recovery.
AB  - Heart failure (HF) is a multifactorial disease brought about by numerous, and
      oftentimes complex, etiological mechanisms. Although well studied, HF continues
      to affect millions of people worldwide and current treatments can only prevent
      further progression of HF. Mitochondria undoubtedly play an important role in the
      progression of HF, and numerous studies have highlighted mitochondrial components
      that contribute to HF. This review presents an overview of the role of
      mitochondrial biogenesis, mitochondrial oxidative stress, and mitochondrial
      permeability transition pore in HF, discusses ongoing studies that attempt to
      address the disease through mitochondrial targeting, and provides an insight on
      how these studies can affect future research on HF treatment. 

PMID- 27032552
TI  - Update on the Pathology and Diagnosis of Interstitial Cystitis/Bladder Pain
      Syndrome: A Review.
AB  - Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder
      discomfort, urinary frequency, urgency, and pelvic pain. The etiology and
      pathogenesis of this condition is still unknown and remains diagnosed by
      exclusion. The histologic findings are also neither specific for diagnosis nor
      correlated with symptoms. However, the definition and diagnostic criteria for the
      condition was established in the last decade. In this paper, we review the
      changes in the definition, terminology, and diagnostic scheme of IC/BPS, and
      summarize the histologic findings. We also briefly discuss some new pathologic
      suggestions and new urinary markers, focusing on the most promising ones. 

PMID- 27032553
TI  - 17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat
      Whole Bladder.
AB  - PURPOSE: To investigate the effect of estrogen on the expression of calcium
      activated potassium (KCa) channels in an overactive bladder rat model. To this
      end, mRNA and protein levels of KCa channel subtypes in the bladder of
      ovariectomized rats were measured by reverse transcription polymerase chain
      reaction and western blotting, respectively. METHODS: Ten-week-old female Sprague
      Dawley rats were divided randomly into 3 groups: sham-operated control group
      (n=11), ovariectomy group (n=11), and the group treated with estrogen after
      ovariectomy (n=12). Rats in the last group were subcutaneously injected with
      17beta-estradiol (50 MUg/kg) every other day for 2 weeks, whereas rats in the
      other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment,
      the whole bladder was excised for mRNA and protein measurements. RESULTS: Protein
      levels of the large-conductance KCa (BK) channels in the ovariectomy group were
      1.5 folds higher than those in the sham-operated control group. However, the
      protein levels of the other KCa channel subtypes did not change significantly
      upon bilateral ovariectomy. Treatment with 17beta-estradiol after ovariectomy
      restored BK channel protein levels to the control value. In contrast, BK channel
      mRNA levels were not significantly affected by either ovariectomy alone or 17beta
      estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and
      protein levels decreased to 75% of control levels upon 17beta-estradiol
      treatment. CONCLUSIONS: These results suggest that 17beta-estradiol may influence
      urinary bladder function by modulating BK and SK3 channel expression.

PMID- 27032554
TI  - Changes in Synaptic Transmission and Long-term Potentiation Induction as a
      Possible Mechanism for Learning Disability in an Animal Model of Multiple
      Sclerosis.
AB  - PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease
      of the central nervous system. It has been shown that memory deficits is common
      in patients with MS. Recent studies using experimental autoimmune
      encephalomyelitis (EAE) as an animal model of MS have shown that indicated that
      EAE causes hippocampal-dependent impairment in learning and memory. Thus far,
      there have been no in vivo electrophysiological reports describing synaptic
      transmission in EAE animals. The aim of the present work is to evaluate the
      synaptic changes in the CA1 region of the hippocampus of EAE rats. METHODS: To
      evaluate changes in synaptic transmission in the CA1 region of the hippocampus of
      EAE rats, field excitatory postsynaptic potentials (fEPSPs) from the stratum
      radiatum of CA1 neurons, were recorded following Schaffer collateral stimulation.
      RESULTS: The results showed that EAE causes deficits in synaptic transmission and
      long-term potentiation (LTP) in the hippocampus. In addition, paired-pulse index
      with a 120 msec interstimulus interval was decreased in the EAE group. These
      findings indicate that EAE might induce suppression in synaptic transmission and
      LTP by increasing the inhibitory effect of GABAB receptors on the glutamate
      mediated EPSP. CONCLUSIONS: In conclusion, influence of inflammation-triggered
      mechanisms on synaptic transmission may explain the negative effect of EAE on
      learning abilities in rats.

PMID- 27032555
TI  - Lower Levels of Urinary Nerve Growth Factor Might Predict Recurrent Urinary Tract
      Infections in Women.
AB  - PURPOSE: To investigate the changes in urinary nerve growth factor (uNGF) levels
      after acute urinary tract infection (UTI) and to assess the role of uNGF in
      predicting UTI recurrence in women. METHODS: Women with uncomplicated,
      symptomatic UTIs were enrolled. Cephalexin 500 mg (every 6 hours) was
      administered for 7-14 days to treat acute UTIs. Subsequently, the patients were
      randomized to receive either sulfamethoxazole/trimethoprim 800 mg/160 mg daily at
      bedtime, or celecoxib 200 mg daily for 3 months and were monitored for up to 12
      months. NGF levels in the urine were determined at baseline, 1, 4, and 12 weeks
      after the initiation of prophylactic therapy, and were compared between women
      with first-time UTIs and recurrent UTIs, sulfamethoxazole/trimethoprim and
      celecoxib-treated women, and no UTI recurrence and UTI recurrence that occurred
      during the follow-up period. Twenty women free of UTIs served as controls.
      RESULTS: A total of 139 women with UTI and 20 controls were enrolled in the
      study, which included 50 women with a first-time UTI and 89 women with recurrent
      UTIs. Thirty-seven women completed the study. Women with recurrent UTIs (n=23)
      had a trend of lower uNGF levels than women with first-time UTIs (n=14). During
      follow-up, 9 women had UTI recurrence. The serial uNGF levels in women with UTI
      recurrence were significantly lower than those in women who did not have UTI
      recurrence during the follow-up period. CONCLUSIONS: The lower levels of uNGF in
      women with recurrent UTI and the incidence of UTI recurrence during follow-up
      suggest that lower uNGF might reflect the defective innate immunity in women with
      recurrent UTI.

PMID- 27032556
TI  - Eight-Year Experience With Botulinum Toxin Type-A Injections for the Treatment of
      Nonneurogenic Overactive Bladder: Are Repeated Injections Worthwhile?
AB  - PURPOSE: To investigate the efficacy and safety of repeated botulinum toxin type
      A (BTX-A) injections for patients with drug-refractory nonneurogenic overactive
      bladder (NNOAB) and explore factors predictive of outcome. METHODS: Data were
      collected from all patients receiving repeated BTX-A injections for drug
      refractory NNOAB between 2004 and 2012. Trigone-sparing injections were
      administered under sedation with antibiotic prophylaxis. Patient characteristics
      including age, sex, preoperative urodynamics, injection number, BTX-A dose,
      complications, and patient global impression of improvement (PGI-I) scores were
      collected. Correlations between patient factors and outcomes were assessed by
      using Pearson's chi-square tests. RESULTS: Fifty-two patients with a mean age of
      67.4 years (range, 26-93 years) received 140 BTX-A injections in total; 33 (64%),
      15 (29%), and 4 patients (7%) received 2, 3 to 4, and 5 to 8 injections,
      respectively. Mean follow-up time was 49 months (range, 9-101 months). Nine
      patients developed urinary tract infection; additionally, 3 patients experienced
      transient urinary retention. Median PGI-I score was 2 out of 7 (interquartile
      range [IQR], 2). For 46 patients, the PGI-I score remained stable with the
      administration of each injection. Pearson chi-square tests revealed that male
      patients or reduced bladder compliance was associated with a higher (worse) PGI-I
      score. Median PGI-I scores for men and women were 3 (IQR, 1) and 2 (IQR, 1),
      respectively; additionally, median PGI-I scores for those with normal bladder
      compliance and those with reduced bladder compliance were 2 (IQR, 2) and 4.5
      (IQR, 1), respectively. Median PGI-I scores and complication rates were the same
      in the older patient (>=70 years) and younger (<70 years) patient cohorts.
      CONCLUSIONS: Efficacy is maintained with repeated BTX-A injections. Patients
      including the elderly show a good degree of tolerability with a low complication
      rate. Male patients or reduced bladder compliance is associated with poorer
      outcomes.

PMID- 27032557
TI  - Assessment of Proportion of Hidden Patients Having Symptoms of Overactive Bladder
      and Why Has It Been Hidden in Female Outpatients Admitted to Hospital.
AB  - PURPOSE: To determine the proportion of patients with undetected symptoms of
      overactive bladder by using the overactive bladder-validated 8 (OAB-V8) screening
      questionnaire and investigate these symptoms were undetected in female patients
      who were hospitalized. METHODS: We invited 2,250 female patients hospitalized in
      the Aegean region of Turkey to answer a self-administered questionnaire. The
      questionnaire included questions on evidence of lower urinary tract symptoms (OAB
      V8), relevant medical history, and demographic data. Patients with a total OAB-V8
      score>=8 were defined as having OAB symptoms. RESULTS: The proportion of patients
      with OAB symptoms in this study was 40.6%. Nearly 57% of the patients with OAB
      symptoms had not been previously admitted to any hospital for lower urinary tract
      symptoms (LUTS). The two most common reasons why women with OAB symptoms did not
      admit themselves to a hospital because of LUTS were as follows: "I did not think
      I had a disease" and "The symptoms did not bother me," with a response rate of
      74.7%. The mean OAB-V8 scores of the patients with these two responses were
      significantly lower than those of the other patients (P<0.001). CONCLUSIONS: This
      is the first study to demonstrate a significant proportion of women with
      undetected OAB symptoms. The main reasons the women did not admit themselves to a
      hospital were their unawareness of the disease and because the LUTS were not
      bothersome. Public awareness programs on this disease may resolve this problem.

PMID- 27032558
TI  - Weakness of the Pelvic Floor Muscle and Bladder Neck Is Predicted by a Slight
      Rise in Abdominal Pressure During Bladder Filling: A Video Urodynamic Study in
      Children.
AB  - PURPOSE: To investigate the significance of slowly rising abdominal pressure
      (SRAP), which is often observed in nonneurogenic children during bladder filling
      in video urodynamic studies (VUDSs). METHODS: The records of patients who
      underwent VUDS from July 2011 to June 2013 were reviewed. SRAP was defined as a
      rising curve over 5 cm H2O from the baseline abdominal pressure during the
      filling phase in VUDS. Bladder descent was defined when the base of the bladder
      was below the upper line of the pubic symphysis. An open bladder neck was defined
      as the opening of the bladder neck during the filling phase. RESULTS: Of the 488
      patients, 285 were male patients. The mean age at VUDS was 3.7 years (range, 0.2
      17.6 years). The VUDS findings were as follows: SRAP, 20.7% (101 of 488);
      descending bladder, 14.8% (72 of 488); and bladder neck opening, 4.3% (21 of
      488). Of the 72 patients with a descending bladder, 84.7% had SRAP. A significant
      difference in the presence of SRAP was found between the descending bladder and
      the normal bladder (P<0.001). Of the 101 patients with SRAP, 40 (39.6%) did not
      have a descending bladder. Of the 40 patients, 14 (35.0%) had a bladder neck
      opening, which was a high incidence compared with the 4.3% in all subjects
      (P<0.001). CONCLUSIONS: SRAP was associated with a descending bladder or a
      bladder neck opening, suggesting that SRAP is a compensatory response to urinary
      incontinence. SRAP may also predict decreased function of the bladder neck or
      pelvic floor muscle.

PMID- 27032559
TI  - Comparison of Predictive Factors for Postoperative Incontinence of Holmium Laser
      Enucleation of the Prostate by the Surgeons' Experience During Learning Curve.
AB  - PURPOSE: To detect predictive factors for postoperative incontinence following
      holmium laser enucleation of the prostate (HoLEP) according to surgeon experience
      (beginner or experienced) and preoperative clinical data. METHODS: Of 224
      patients, a total of 203 with available data on incontinence were investigated.
      The potential predictive factors for post-HoLEP incontinence included clinical
      factors, such as patient age, and preoperative urodynamic study results,
      including detrusor overactivity (DO). We also classified the surgeons performing
      the procedure according to their HoLEP experience: beginner (<21 cases) and
      experienced (>=21 cases). RESULTS: Our statistical data showed DO was a
      significant predictive factor at the super-short period (the next day of catheter
      removal: odds ratio [OR], 3.375; P=0.000). Additionally, patient age, surgeon
      mentorship (inverse correlation), and prostate volume were significant predictive
      factors at the 1-month interval after HoLEP (OR, 1.072; P=0.004; OR, 0.251;
      P=0.002; and OR, 1.008; P=0.049, respectively). With regards to surgeon
      experience, DO and preoperative International Prostate Symptom Score (inverse) at
      the super-short period, and patient age and mentorship (inverse correlation) at
      the 1-month interval after HoLEP (OR, 3.952; P=0.002; OR, 1.084; P=0.015; and
      OR,1.084; P=0.015; OR, 0.358; P=0.003, respectively) were significant predictive
      factors for beginners, and first desire to void (FDV) at 1 month after HoLEP (OR,
      1.009; P=0.012) was a significant predictive factor for experienced surgeons in
      multivariate analysis. CONCLUSIONS: Preoperative DO, IPSS, patient age, and
      surgeon mentorship were significant predictive factors of postoperative patient
      incontinence for beginner surgeons, while FDV was a significant predictive
      factors for experienced surgeons. These findings should be taken into account by
      surgeons performing HoLEP to maximize the patient's quality of life with regards
      to urinary continence.

PMID- 27032560
TI  - Effect of Nerve-Sparing Radical Prostatectomy on Urinary Continence in Patients
      With Preoperative Erectile Dysfunction.
AB  - PURPOSE: We aimed to assess whether nerve-sparing radical prostatectomy (nsRP) is
      associated with improved recovery of urinary continence compared to non-nerve
      sparing radical prostatectomy (nnsRP) in patients with localized prostate cancer
      and preoperative erectile dysfunction. METHODS: A total of 360 patients with
      organ-confined prostate cancer and an International Index of Erectile Function
      score of less than 17 were treated with nsRP or nnsRP in Seoul St. Mary's
      Hospital. Patients who received neoadjuvant or adjuvant androgen deprivation
      therapy or had a history of prostate-related surgery were excluded. Recovery of
      urinary continence was assessed at 0, 1, 3, 6, and 12 months. Postoperative
      recovery of continence was defined as zero pad usage. The association between
      nerve-sparing status and urinary continence was assessed by using univariate and
      multivariate Cox regression analyses after controlling for known predictive
      factors. RESULTS: Urinary continence recovered in 279 patients (77.5%) within the
      mean follow-up period of 22.5 months (range, 6-123 months). Recovery of urinary
      continence was reported in 74.6% and 86.4% of patients after nnsRP and nsRP,
      respectively, at 12 months (P=0.022). All groups had comparable perioperative
      criteria and had no significant preoperative morbidities. Age, American Society
      of Anesthesiologists score, and nerve-sparing status were significantly
      associated with recovery of urinary continence on univariate analysis. On
      multivariate analysis, age (hazard ratio [HR], 1.254; 95% confidence interval
      [CI], 1.002-1.478; P=0.026) and nerve-sparing status (HR, 0.713; 95% CI, 0.548
      0.929; P=0.012) were independently associated with recovery of urinary
      continence. CONCLUSIONS: nsRP, as compared to nnsRP, improves recovery rates of
      urinary incontinence and decreases surgical morbidity without compromising
      pathologic outcomes.

PMID- 27032561
TI  - Clinical Significance of the Resistive Index of Prostatic Blood Flow According to
      Prostate Size in Benign Prostatic Hyperplasia.
AB  - PURPOSE: The authors evaluated the relationships between the clinical factors and
      resistive indexes (RIs) of prostate and urethral blood flows by using power
      Doppler transrectal ultrasonography (PDUS) in men with benign prostatic
      hyperplasia (BPH). METHODS: The data of 110 patients with BPH and lower urinary
      tract symptoms (LUTS) treated between January 2015 and July 2015 were
      prospectively collected. PDUS was used to identify the capsular and urethral
      arteries of the prostate in order to measure RIs. International Prostate Symptom
      Score (IPSS), maximal flow rate (Qmax), total prostate volume (TPV), transition
      zone volume (TZV), transition zone index (=TZV/TPV), presence of intravesical
      prostatic protrusion (IPP), and the RIs of capsular and urethral arteries were
      evaluated for all of the patients by one urologist. RESULTS: The 110 patients
      were categorized according to IPSS (mild symptoms, 0-7; moderate symptoms, 8-19;
      and severe symptoms, 20-35), Qmax (<10 and >=10 mL/sec), TPV (<30 and >=30 mL),
      and presence or absence of IPP. No significant relationship was found between the
      mean RI of any artery and IPSS or Qmax. The mean RIs of the urethral artery, and
      left and right capsular arteries were significantly dependent on prostate size
      and the presence of IPP. CONCLUSIONS: RI obtained by using PDUS correlated with
      the presence of IPP and prostate size. The RI of prostate blood flow can be used
      as a noninvasive diagnostic tool for BPH with LUTS.

PMID- 27032562
TI  - Intravesical OnabotulinumtoxinA Injection for Overactive Orthotopic Ileal
      Neobladder: Feasibility and Efficacy.
AB  - The efficacy of intravesical onabotulinumtoxinA (BTXA) in the treatment of
      overactive bladder (OAB) has been well documented. The use of BTXA injection in
      orthotopic neobladders is yet to be studied. We present 4 cases of patients
      injected with intravesical BTXA for overactive orthotopic ileal neobladder. We
      recorded patient demographics, presenting and follow-up symptoms, urodynamic
      profiles, and Patient Global Impression of Improvement (PGI-I) scores. The 4
      patients reported varying degrees of subjective improvements in the symptoms,
      including urgency, urge incontinence, and pad usage. Mean follow-up duration was
      8.3 months (range, 5-14 months). Average PGI-I score was 3 ("a little better")
      (range, 2-4). To our knowledge, the current study is the first case series
      examining BTXA injection for orthotopic neobladder overactivity. BTXA injection
      yielded varying degrees of objective and subjective improvements, without
      significant complications. Intravesical BTXA injection is feasible and may be
      considered as a potential treatment alternative for OAB in orthotopic
      neobladders, although further study is warranted. 

PMID- 27032563
TI  - In vitro and in vivo evaluation of sandwich-like mesoporous silica nanoflakes as
      promising anticancer drug delivery system.
AB  - We present the new promising nanostructure- sandwich-like mesoporous silica
      nanoflakes synthesized on graphene oxide sheets core. In the first step
      biocompatibility of the nanoflakes with PEG and without functionalization in
      human fibroblast, melanoma and breast cancer cells was assessed. In order to
      define the cellular uptake in vitro and biodistribution in vivo the
      nanostructures were labelled with fluorescent dye. In the next step, the silica
      nanostructures were filled by the anticancer drug- methotrexate (MTX) and
      cytotoxicity of the complex in reference to MTX was evaluated. The WST-1 assay
      shows mild, but concentration dependent, cytotoxicity of the nanoflakes, most
      significant for the non-functionalized structures. PEG-modified silica nanoflakes
      didn't produce a disruption of cell membranes and lactate dehydrogenase (LDH)
      release. Cell imaging revealed efficient internalization of the silica nanoflakes
      in cells. Ex vivo organ imaging showed high accumulation of the nanostructures in
      lungs, bladder and gall bladder, whereas confocal imaging revealed wide nanoflake
      distribution in all tested tissues, especially at 1h and 4h post intravenous
      injection. Cytotoxicity of the nanoflake-MTX complex in reference to MTX showed
      similar cytotoxic potential against cancer cells. These findings may provide
      useful information for designing drug delivery systems, which may improve
      anticancer efficacy and decrease side effects. 

PMID- 27032564
TI  - FITC-Dextran entrapped and silica coated gadolinium oxide nanoparticles for
      synchronous optical and magnetic resonance imaging applications.
AB  - We report, microemulsion mediated synthesis of FITC-dextran dye entrapped and
      silica coated Gd2O3 nanoparticles (NPs) for dual purpose of optical and magnetic
      resonance imaging, in the present study. TEM image revealed that the average size
      of the NPs is 18nm and hydrodynamic diameter of the particles as measured by DLS
      comes out to be about 16nm. Gd2O3 core show paramagnetism which is affirmed by
      the NMR line broadening effect on neighboring water proton spectrum and also by
      magnetization curve obtained in VSM analysis. The fluorescence of the entrapped
      dye is confirmed by the UV-vis and fluorescence spectroscopy. Nanoencapsulation
      of FITC-dextran fluorophore was found to increase its optical activity and
      provided a blanket against quenching. Moreover, TGA data revealed that entrapment
      of dye imparts thermal stability to it and enhances its fluorescence in
      comparison to bare dye. The release kinetic pattern (at pH 7.4) of the entrapped
      dye revealed that these particles behave as non-releasing system. The in-vitro
      cell viability (SRB) assay of the particles done on normal cell line (HEK-293) as
      well as cancerous cell line (A-549) indicated non-cytotoxic nature of the
      particles. In a nut-shell, these particles have the potential to be efficiently
      used for optical and magnetic resonance imaging. We anticipate that further
      optimization of these particles can be done by either conjugating or entrapping a
      drug for targeted drug delivery which would open more prospective options in
      biomedical field. 

PMID- 27032565
TI  - Effect of the deformability of guest particles on the tensile strength of tablets
      from interactive mixtures.
AB  - In this study, we investigated the influence of deformability of specifically
      engineered guest particles on the tensile strength of tablets of interactive
      mixtures. The binder polyvinylpyrrolidone (PVP) of different molecular weights
      were spray dried with l-leucine to create guest particle formulations. The guest
      particle formulations were characterized by their particle size, surface l
      leucine concentration and glass transition temperature (Tg). These spray-dried
      particles were then blended with paracetamol to form interactive mixtures, which
      were compacted into tablets and tablet tensile strength and elastic recovery were
      determined. The guest particles had particle diameters in the range of 1-10MUm,
      and surfaces that were l-leucine enriched. The Tg of guest particle formulations
      increased with increasing molecular weight of the PVP. All the guest particle
      formulations formed an observed homogeneous interactive mixture with paracetamol.
      The tensile strength of the tablets of interactive mixtures increased with
      decreasing Tg of the guest particles. In these interactive mixtures, higher
      tensile strength was also associated with lower tablet elastic recovery. The
      elastic recovery of the tablets showed a correlation with the elastic recovery of
      the tablets of guest particles. Thus, our results indicated that the
      deformability of guest particles dictates the tensile strength of the tablets of
      these interactive mixtures.

PMID- 27032566
TI  - Impact of PAMAM delivery systems on signal transduction pathways in vivo:
      Modulation of ERK1/2 and p38 MAP kinase signaling in the normal and diabetic
      kidney.
AB  - The in vivo impact of two generation 6 cationic polyamidoamine (PAMAM) dendrimers
      on cellular signaling via extracellular-regulated kinase 1/2 (ERK1/2) and p38
      mitogen-activated protein kinase (p38 MAPK), as well as their relationship to
      epidermal growth factor receptor (EGFR), were studied in the normal and/or
      diabetic rat kidney. A single 10mg/kg/i.p administration of Polyfect (PF; with an
      intact branching architecture) or Superfect (SF; with a fragmented branching
      architecture) modulated renal ERK1/2 and p38 MAPK phosphorylation in a dendrimer
      specific and animal model-dependent manner. AG1478 treatment (a selective EGFR
      inhibitor) confirmed that renal ERK1/2 and p38 MAPK signaling was downstream of
      EGFR. Surprisingly, both PAMAMs induced hyperphosphorylation of ERK1/2 and p38
      MAPK (at 1 or 5mg/kg) despite inhibiting EGFR phosphorylation in the diabetic
      kidney. PAMAMs did not alter renal morphology but their effects on p38 MAPK and
      EGFR phosphorylation were reversed by ex vivo treatment of kidneys with the anti
      oxidant, Tempol. Thus, PAMAMs can intrinsically modulate signaling of mitogen
      activated protein kinases (MAPKs) depending on the type of dendrimer (fragmented
      vs intact branching architecture) and animal model (normal vs diabetic) used and
      likely occurs via an EGFR-independent and oxidative-stress dependent mechanism.
      These findings might have important toxicological implications for PAMAM-based
      delivery systems.

PMID- 27032567
TI  - Biocompatible hybrid silica nanobiocomposites for the efficient delivery of anti
      staphylococcal drugs.
AB  - This work reports the non-surfactant templated synthesis and characterization of
      a new tyrosine-silica/antibiotics (TyR-SiO2/ATBs) nanocomposite, as well as both
      in vitro and in vivo cytotoxicity and antimicrobial activity against the
      microbial pathogen Staphylococcus aureus. The in vitro microbiological tests
      proved that the obtained nanobiostructure significantly enhance the antimicrobial
      activity of three commonly used antibiotics against S. aureus (i.e. erythromycin
      (ERI), gentamicin (GEN), and cloxacillin (CLO)) as revealed by the increased
      diameters of the growth inhibition zones and the decreased minimal inhibitory
      concentration values, as well as by the inhibitory effect of sub-lethal
      antibiotic concentrations on the ability of the respective pathogenic strains to
      adhere and colonize different substrata. These results, correlated with the lack
      of toxicity against mesenchymal stem cells along with an appropriate in vivo
      biodistribution highlight the promising therapeutic potential of this carrier
      that allows a decrease of the required active doses while significantly lessening
      the harmful side effects of the medication on the host organism. 

PMID- 27032569
TI  - Majocchi Granuloma of the Breast: A Rare Clinical Entity.

PMID- 27032568
TI  - Exposure to an inflammatory challenge enhances neural sensitivity to negative and
      positive social feedback.
AB  - Inflammation, part of the body's innate immune response, can lead to "sickness
      behaviors," as well as alterations in social and affective experiences. Elevated
      levels of pro-inflammatory cytokines have been associated with increased neural
      sensitivity to social rejection and social threat, but also decreased neural
      sensitivity to rewards. However, recent evidence suggests that inflammation may
      actually enhance sensitivity to certain social rewards, such as those that signal
      support and care. Despite a growing interest in how inflammation influences
      neural reactivity to positive and negative social experiences, no known studies
      have investigated these processes in the same participants, using a similar task.
      To examine this issue, 107 participants were randomly assigned to receive either
      placebo or low-dose endotoxin, which safely triggers an inflammatory response.
      When levels of pro-inflammatory cytokines were at their peak, participants were
      scanned using fMRI while they received positive, negative, and neutral feedback
      from an "evaluator" (actually a confederate) about how they came across in an
      audio-recorded interview. In response to negative feedback (vs. neutral),
      participants in the endotoxin condition showed heightened neural activity in a
      number of threat-related neural regions (i.e., bilateral amygdala, dorsal
      anterior cingulate cortex) and a key mentalizing-related region (i.e.,
      dorsomedial PFC), compared to placebo participants. Interestingly, when receiving
      positive feedback (vs. neutral), endotoxin (vs. placebo) led to greater neural
      activity in the ventral striatum and ventromedial PFC, regions often implicated
      in processing reward, as well as greater activity in dorsomedial PFC. Together,
      these results reveal that individuals exposed to an inflammatory challenge are
      more "neurally sensitive" to both negative and positive social feedback,
      suggesting that inflammation may lead to a greater vigilance for both social
      threats and social rewards. 

PMID- 27032570
TI  - Monetary incentive moderates the effect of implicit fear on effort-related
      cardiovascular response.
AB  - Integrating the implicit-affect-primes-effort model (Gendolla, 2012, 2015) with
      the principles of motivational intensity theory (Brehm & Self, 1989) we
      investigated if the effort mobilization deficit observed in people exposed to
      fear primes (vs. anger primes) in a difficult short-term memory task could be
      compensated by high monetary incentive. Effort was operationalized as cardiac
      response. We expected that fear primes should lead to the strongest cardiac pre
      ejection period (PEP) reactivity when incentive was high (high subjective demand
      and high justified effort) and to the weakest response when incentive was low
      (high subjective demand but only low justified effort). PEP reactivity in the
      anger-prime conditions should fall in between (high but feasible demand). We
      obtained the predicted pattern on responses of PEP and systolic blood pressure.
      The present findings show for the first time that the effort mobilization deficit
      of participants exposed to fear primes in a difficult cognitive task could be
      compensated by a high incentive.

PMID- 27032571
TI  - Role of miRNAs and alternative mRNA 3'-end cleavage and polyadenylation of their
      mRNA targets in cardiomyocyte hypertrophy.
AB  - miRNAs play critical roles in heart disease. In addition to differential miRNA
      expression, miRNA-mediated control is also affected by variable miRNA processing
      or alternative 3'-end cleavage and polyadenylation (APA) of their mRNA targets.
      To what extent these phenomena play a role in the heart remains unclear. We
      sought to explore miRNA processing and mRNA APA in cardiomyocytes, and whether
      these change during cardiac hypertrophy. Thoracic aortic constriction (TAC) was
      performed to induce hypertrophy in C57BL/6J mice. RNA extracted from
      cardiomyocytes of sham-treated, pre-hypertrophic (2 days post-TAC), and
      hypertrophic (7 days post-TAC) mice was subjected to small RNA- and poly(A)-test
      sequencing (PAT-Seq). Differential expression analysis matched expectations;
      nevertheless we identified ~400 mRNAs and hundreds of noncoding RNA loci as
      altered with hypertrophy for the first time. Although multiple processing
      variants were observed for many miRNAs, there was little change in their relative
      proportions during hypertrophy. PAT-Seq mapped ~48,000 mRNA 3'-ends, identifying
      novel 3' untranslated regions (3'UTRs) for over 7000 genes. Importantly,
      hypertrophy was associated with marked changes in APA with a net shift from
      distal to more proximal mRNA 3'-ends, which is predicted to decrease overall
      miRNA repression strength. We independently validated several examples of 3'UTR
      proportion change and showed that alternative 3'UTRs associate with differences
      in mRNA translation. Our work suggests that APA contributes to altered gene
      expression with the development of cardiomyocyte hypertrophy and provides a rich
      resource for a systems-level understanding of miRNA-mediated regulation in
      physiological and pathological states of the heart.

PMID- 27032572
TI  - Dosimetric predictors of hematologic toxicity in patients undergoing concurrent
      gemcitabine-based chemoradiation for localized pancreatic cancer.
AB  - PURPOSE: This study was undertaken to identify parameters associated with
      hematologic toxicity or chemotherapy dose modification in patients undergoing
      concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer.
      METHODS AND MATERIALS: We reviewed patients with localized pancreatic cancer
      undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of
      nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic
      indices. The T11-L3 vertebrae were contoured as bone marrow region at risk.
      Linear and logistic regression models were used to test associations between
      dosimetric parameters and gemcitabine dose modification or hematologic toxicity
      during or within 3 months following CRT. Receiver operator curves were generated
      to identify threshold doses for hematologic toxicity. RESULTS: Forty-nine
      patients were included. During CRT, the maximum thoracolumbar dose was associated
      with grade 2+ neutropenia during CRT (P = .017) and the volume receiving 5 Gy
      (V5) was associated with grade 2+ leukopenia (P = .041). Post-CRT, thoracolumbar
      mean dose (P = .015), V5 (P = .01), and V10 (P = .012) were associated with
      increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar
      maximum dose (P = .045) and V5 (P = .045) were associated with grade 2+
      neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean
      dose (P = .046), V5 (P = .019), and V10 (P = .037) were associated with increased
      grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified
      as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose
      of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post
      CRT, there was a trend toward increased dose modifications with increased V5 (P =
      .065). CONCLUSIONS: In our dataset, the thoracolumbar mean dose, maximum dose,
      V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in
      patients with localized pancreatic cancer. Because of the high rates of distant
      failure and importance of systemic therapy in these patients, this may be an
      important consideration during treatment planning.

PMID- 27032573
TI  - Improving target volume delineation in intact cervical carcinoma: Literature
      review and step-by-step pictorial atlas to aid contouring.
AB  - PURPOSE: Accurate delineation of target volume and normal tissue is critical for
      intensity modulated radiation therapy (IMRT) use in cervical cancer. Phase III
      Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard
      Chemoradiation versus Standard Chemoradiation Alone in Patients With Locally
      Advanced Cervical Cancer (INTERLACE) radiation therapy quality assurance (RTQA)
      has highlighted significant interobserver delineation variation. Prescriptive
      guidelines reduce interobserver variation in other cancers. METHODS AND
      MATERIALS: A literature search using PubMed/Medline database of guidelines for
      target anatomy delineation in cervical cancer was undertaken. Differences in
      practice in these publications and INTERLACE trial RTQA were identified.
      Consensus best practice delineation was derived and a pictorial atlas produced.
      The proportion of outlines complying with protocol in test and real-time cases
      was compared before and after atlas implementation within the INTERLACE RTQA
      pack. RESULTS: Seven key papers were reviewed. Eleven areas of variation were
      identified. These included the definition and editing of bowel, definition of the
      femur, vagina, parametria, inferior and superior nodal borders, nodal clinical
      target volume (CTV) editing, para-aortic nodal CTV definition, and the margin to
      be used around enlarged nodes. The average proportion of outlines (of 4; primary
      CTV, nodal CTV, bladder, rectum) complying with protocol in test and real-time
      cases improved from 1.8 to 2.7 (difference, 0.9; 95% confidence interval, 0.3
      1.5; P = .003) with atlas use. CONCLUSION: Differences exist in the published
      literature and clinical practice. This pictorial atlas reflects consensus
      recommendations and is now available to INTERLACE participating centers. Atlas
      use has reduced interobserver delineation variation in this trial setting.

PMID- 27032574
TI  - Inhibition of MAPK signaling pathways enhances cell death induced by 5
      Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells.
AB  - Combination of a photosensitizer, 5-aminolevulinic acid (ALA), with photodynamic
      therapy (PDT) has been widely used to treat skin squamous cell carcinoma (SCC).
      However, a portion of SCC patients do not respond well to PDT. The molecular
      reason for this resistance is not clear. We hypothesize that mitogen-activated
      phosphorylation kinase (MAPK) plays a key role in mediating SCC resistance to
      PDT. To determine whether inhibition of MAPK signaling enhances the anti-tumor
      effect of ALA-PDT in SCC. The human squamous carcinoma cell line, SCL-1, was
      either untreated or treated with various combinations of ALA, PDT light source
      and inhibitors of MAPK signaling components. ALA-PDT treatment significantly
      decreased cell viability, increased the percentage of annexin-V positive cells
      and resulted in formation of apoptotic bodies. ALA-PDT treated cells showed
      increased levels of p-MEK, p-ERK1/2, p-p38, p-Elk-1, p-JNK and p-c-Jun. Addition
      of inhibitors for ERK1/2 (PD98059), p38 (SB203580) and JNK (SP60125) reversed the
      changes and led to a more dramatic decrease in SCL-1 cell viability than seen
      with ALA-PDT alone. Inhibition of the MAPK pathway enhances the cytotoxic effect
      of ALA-PDT on SCL-1. 

PMID- 27032575
TI  - A homeobox protein, NKX6.1, up-regulates interleukin-6 expression for cell growth
      in basal-like breast cancer cells.
AB  - Among breast cancer subtypes, basal-like breast cancer is particularly
      aggressive, and research on the molecules involved in its pathology might
      contribute to therapy. In this study, we found that expression of NKX6.1, a
      homeobox transcription factor, is higher in basal-like breast cancer than in
      other subtypes. In loss-of-function experiments on basal-like breast cancer cell
      lines, NKX6.1-depleted cells exhibited reduced cell growth. Because cytokine
      interleukin-6 (IL-6) is expressed in basal-like breast cancer, and increases cell
      growth, we analyzed expression levels of IL6, an IL-6 gene, and observed reduced
      IL6 expression in NKX6.1-depleted cells. In a reporter assay, IL6 promoter
      activity was reduced by loss of NKX6.1 function. A pull-down assay showed that
      NKX6.1 binds to the proximal region in IL6 promoter. These results indicate that
      NKX6.1 directly up-regulates IL6 expression. To investigate further, we
      established cells with forced expression of IL-6. We observed that exogenous IL-6
      expression restored the reduced cell growth of NKX6.1-depleted cells.
      Furthermore, orthotopic xenografts showed that NKX6.1-depleted cells lost the
      capacity for tumor formation. We therefore conclude that NKX6.1 is a factor for
      IL-6-regulated growth and tumor formation in basal-like breast cancer. Our
      findings facilitate profound understanding of basal-like breast cancer, and the
      development of suitable therapy.

PMID- 27032576
TI  - Involvement of PI3K/Akt, ERK and p38 signaling pathways in emodin-mediated
      extrinsic and intrinsic human hepatoblastoma cell apoptosis.
AB  - As a natural anthraquinone derivative, 1,3,8-trihydroxy-6-methylanthraquinone,
      known as emodin, has recently been reported to possess potential chemopreventive
      capacity, but the underlying molecular mechanism of its hepatocyte toxicity
      remains poorly clarified. The present research indicated that emodin targeted
      HepG2 cells without being cytotoxic to primary human hepatocyte cells in
      comparison with chrysophanol and rhein. The anti-proliferative effect of emodin
      was ascribed to occurrence of apoptosis, which characterized by higher ethidium
      bromide signal, brighter DAPI fluorescence, cleavages of procaspase-3 and poly
      (ADP-ribose) polymerase as well as quantitative result from Annexin V-FITC/PI
      double staining. Furthermore, emodin improved Bax/Bcl-2 ratio, elicited
      disruption of mitochondrial membrane potential and promoted efflux of cytochrome
      c to cytosol, indicative of features of mitochondria-dependent apoptotic signals.
      Emodin concurrently led to activations of Fas, Fas-L, caspase-8 and tBid, which
      provoked death receptor apoptotic signals. Notably, activated tBid relayed the
      Fas apoptotic signal to the mitochondrial pathway. Besides, emodin effectively
      attenuated phosphorylations of Akt and ERK and promoted phosphorylation of p38.
      Inhibitions of PI3K/Akt and ERK and activation of p38 mediated emodin-induced
      apoptosis through modulating the mitochondrial pathway and/or death receptor
      pathway. Additionally, there was a cross-talk between PI3K/Akt and MAPKs pathways
      in emodin-induced apoptosis. 

PMID- 27032577
TI  - Comment on: Koppelman SJ, Jayasena S, Luykx D, Schepens E, Apostolovic D, de Jong
      GA, et al. Allergenicity attributes of different peanut market types. Food and
      chemical toxicology: An international journal published for the British
      Industrial Biological Research Association 2016.

PMID- 27032578
TI  - LUIGI PROVASOLI AWARD RECIPIENTS.

PMID- 27032579
TI  - TESTING THE EFFECTS OF OCEAN ACIDIFICATION ON ALGAL METABOLISM: CONSIDERATIONS
      FOR EXPERIMENTAL DESIGNS(1).
AB  - Ocean acidification describes changes in the carbonate chemistry of the ocean due
      to the increased absorption of anthropogenically released CO2 . Experiments to
      elucidate the biological effects of ocean acidification on algae are not
      straightforward because when pH is altered, the carbon speciation in seawater is
      altered, which has implications for photosynthesis and, for calcifying algae,
      calcification. Furthermore, photosynthesis, respiration, and calcification will
      themselves alter the pH of the seawater medium. In this review, algal
      physiologists and seawater carbonate chemists combine their knowledge to provide
      the fundamental information on carbon physiology and seawater carbonate chemistry
      required to comprehend the complexities of how ocean acidification might affect
      algae metabolism. A wide range in responses of algae to ocean acidification has
      been observed, which may be explained by differences in algal physiology,
      timescales of the responses measured, study duration, and the method employed to
      alter pH. Two methods have been widely used in a range of experimental systems:
      CO2 bubbling and HCl/NaOH additions. These methods affect the speciation of
      carbonate ions in the culture medium differently; we discuss how this could
      influence the biological responses of algae and suggest a third method based on
      HCl/NaHCO3 additions. We then discuss eight key points that should be considered
      prior to setting up experiments, including which method of manipulating pH to
      choose, monitoring during experiments, techniques for adding acidified seawater,
      biological side effects, and other environmental factors. Finally, we consider
      incubation timescales and prior conditioning of algae in terms of regulation,
      acclimation, and adaptation to ocean acidification. 

PMID- 27032580
TI  - LAMINARIOCOLAX SP. (PHAEOPHYCEAE) ASSOCIATED WITH GALL DEVELOPMENTS IN LESSONIA
      NIGRESCENS (PHAEOPHYCEAE)(1).
AB  - As part of a long-term study on the biology and ecology of the intertidal kelp
      Lessonia nigrescens Bory, we report on the occurrence of gall development on this
      alga, identified the possible causal agent, and assessed the extent of the
      phenomenon in two wild stands of the host. Our results showed that galls
      affecting natural populations of L. nigrescens were associated with the infection
      by a filamentous brown algal endophyte of the genus Laminariocolax. Assignment to
      Laminariocolax of the endophytes isolated from cultured gall tissue was based on
      the (i) high internal transcribed spacer 1 (ITS1) sequence similarity and
      phylogenetic relationship between the Chilean isolates and several species of the
      genus Laminariocolax endophytic in other kelps, (ii) reproductive and vegetative
      features of the endophyte in culture, and (iii) anatomical agreement of fully
      developed galls of Lessonia with those described for other kelp galls caused by
      endophytic members of Laminariocolax. Unequivocal identification at the species
      level of the endophytes infecting Lessonia, however, awaits further studies. 

PMID- 27032581
TI  - DISTRIBUTION OF OLIGOPEPTIDE CHEMOTYPES OF THE CYANOBACTERIUM PLANKTOTHRIX AND
      THEIR PERSISTENCE IN SELECTED LAKES IN FENNOSCANDIA(1).
AB  - Eighty-seven Planktothrix (Anagnostidis and Komarek 1988) strains isolated from
      13 lakes in Scandinavia and Finland between 1964 and 2007 were screened for
      oligopeptides. Forty-six individual compounds were detected in total, belonging
      to the structural classes anabaenopeptins (six variants), aeruginosins (six
      variants), cyanopeptolins (21 variants), microcystins (five variants),
      microginins (two variants), and microviridins (two variants). Oscillatorin was
      also found. Three additional compounds could not be assigned to known
      oligopeptide classes. Thirty oligopeptides have not been described in previous
      studies. Of these new compounds, five were aeruginosins and 20 cyanopeptolins.
      The number of oligopeptides per strain ranged from one to 13. No oligopeptide
      free strains were found, suggesting that oligopeptide production is vital for
      Planktothrix. On the basis of their oligopeptide patterns, the Planktothrix
      strains of the present study were assigned to 17 chemotypes. Three major
      chemotypes occurred in up to six lakes. One chemotype occurred in lakes around
      the city of Oslo (Norway), on the Finnish island Fasta Aland, which is situated
      in the Baltic Sea, and on the Finnish mainland. This wide distribution suggests
      that chemotypes can be subjects of recurrent dispersal and/or strong directional
      selection. Lake size, maximum depth, and nutrient availability appeared to be of
      minor importance for the ability of some chemotypes to colonize a water body
      successfully as long as the general requirements of Planktothrix were met. Four
      chemotypes were reisolated from the Oslo lake district over a period of 33-40
      years, suggesting that they have been members of local Planktothrix populations
      for decades. 

PMID- 27032582
TI  - PHENOTYPIC PLASTICITY RECONCILES INCONGRUOUS MOLECULAR AND MORPHOLOGICAL
      TAXONOMIES: THE GIANT KELP, MACROCYSTIS (LAMINARIALES, PHAEOPHYCEAE), IS A
      MONOSPECIFIC GENUS(1).
AB  - The giant kelp genus Macrocystis C. Agardh (Laminariales, Phaeophyceae) is one of
      the world's most ecologically and economically important seaweed taxa, yet its
      taxonomy remains uncertain. Although the genus currently contains four accepted
      species based on variable holdfast and blade morphology [M. pyrifera (L.) C.
      Agardh, M. integrifolia Bory, M. angustifolia Bory, and M. laevis C. H. Hay],
      numerous recent studies on Macrocystis interfertility, genetic relatedness, and
      morphological plasticity all suggest that the genus is monospecific. We reviewed
      this evidence and present an explanation for the extreme phenotypic plasticity
      that results in morphological variability within Macrocystis, driven by the
      effects of environmental factors on early development of macroscopic sporophytes.
      We propose that the genus be collapsed back to a single species, with
      nomenclatural priority given to M. pyrifera. 

PMID- 27032583
TI  - THE CONCHOCELIS OF PORPHYRA HAITANENSIS (RHODOPHYTA) IS PROTECTED FROM HARMFUL UV
      RADIATION BY THE COVERING CALCAREOUS MATRIX(1).
AB  - Previous study has shown that Porphyra conchocelis is sensitive to high levels of
      PAR (400-700 nm) as well as ultraviolet radiation (UVR: 280-400 nm), resulting in
      high inhibition of photosynthesis. However, little is known about whether the
      inner covering layer of the shell, in which the conchocelis lives, may provide
      protection against solar UVR. Our study indicates that the covering calcareous
      matrix is about 0.06 mm thick, transmitting 63, 47, and 28% of PAR, ultraviolet
      radiation A (UVA: 315-400 nm), and ultraviolet radiation B (UVB: 280-315 nm),
      respectively. We used a shading layer that simulated the above transmissions, and
      the effective quantum yield of PSII and photosynthetic carbon fixation in the
      conchocelis increased to greater extents in the presence of UVA or UVB.
      Attenuation of UVA by 19% and UVB by 37% due to the shading layer increased the
      PSII yield by 44%-77% and photosynthetic carbon fixation by about 60%. Our study
      clearly shows that the photosynthetic machinery of Porphyra haitanensis T. J.
      Chang et B. F. Zheng conchocelis was efficiently protected from harmful UVR by
      the covering calcareous matrix. 

PMID- 27032584
TI  - ECOLOGICAL DIFFERENTIATION BETWEEN SYMPATRIC PSEUDOCRYPTIC SPECIES IN THE
      ESTUARINE BENTHIC DIATOM NAVICULA PHYLLEPTA (BACILLARIOPHYCEAE)(1).
AB  - The occurrence of cryptic and pseudocryptic species, often living in sympatry, is
      widespread among microalgae. This phenomenon raises important questions about
      niche partitioning between these closely related species. To date, however, few
      studies have addressed the ecological mechanisms underlying sympatry in cryptic
      and pseudocryptic species. As a result, we have only a limited understanding of
      the factors that govern their distribution along environmental gradients. Here,
      we used the ribosomal internal transcribed spacer (ITS), 18S rRNA gene, and the
      RUBISCO LSU (rbcL) chloroplast gene sequence data together with cell wall
      morphology to show that estuarine populations of the widespread and common
      benthic diatom Navicula phyllepta Kutz. consist of pseudocryptic species. Growth
      rate measurements in function of salinity showed that N. phyllepta strains
      assigned to the different species differed in their tolerance to low salinities
      (<5 practical salinity units, psu), which was reflected by their different (but
      widely overlapping) distribution in the Westerschelde estuary (the Netherlands).
      Multiple regression analyses of the factors determining the abundance of the
      different species in field samples revealed that, in addition to salinity,
      sediment type and ammonium concentrations were probably equally important. Our
      results show that N. phyllepta sensu lato comprises different species with
      specialized ecophysiological characteristics rather than generalists with a broad
      adaptability to different environmental conditions. 

PMID- 27032585
TI  - THE SHORT-TERM EFFECT OF IRRADIANCE ON THE PHOTOSYNTHETIC PROPERTIES OF ANTARCTIC
      FAST-ICE MICROALGAL COMMUNITIES(1).
AB  - Although sea-ice represents a harsh physicochemical environment with steep
      gradients in temperature, light, and salinity, diverse microbial communities are
      present within the ice matrix. We describe here the photosynthetic responses of
      sea-ice microalgae to varying irradiances. Rapid light curves (RLCs) were
      generated using pulse amplitude fluorometry and used to derive photosynthetic
      yield (PhiPSII ), photosynthetic efficiency (alpha), and the irradiance (Ek ) at
      which relative electron transport rate (rETR) saturates. Surface brine algae from
      near the surface and bottom-ice algae were exposed to a range of irradiances from
      7 to 262 MUmol photons . m(-2)  . s(-1) . In surface brine algae, PhiPSII and
      alpha remained constant at all irradiances, and rETRmax peaked at 151 MUmol
      photons . m(-2)  . s(-1) , indicating these algae are well acclimated to the
      irradiances to which they are normally exposed. In contrast, PhiPSII , alpha, and
      rETRmax in bottom-ice algae reduced when exposed to irradiances >26 MUmol photons
      . m(-2)  . s(-1) , indicating a high degree of shade acclimation. In addition,
      the previous light history had no significant effect on the photosynthetic
      capacity of bottom-ice algae whether cells were gradually exposed to target
      irradiances over a 12 h period or were exposed immediately (light shocked). These
      findings indicate that bottom-ice algae are photoinhibited in a dose-dependent
      manner, while surface brine algae tolerate higher irradiances. Our study shows
      that sea-ice algae are able to adjust to changes in irradiance rapidly, and this
      ability to acclimate may facilitate survival and subsequent long-term acclimation
      to the postmelt light regime of the Southern Ocean. 

PMID- 27032586
TI  - EXTRACELLULAR ENZYMES OF THE MICROCYSTIS AERUGINOSA PCC 7813 STRAIN ARE INHIBITED
      IN THE PRESENCE OF HYDROQUINONE AND PYROGALLOL, ALLELOCHEMICALS PRODUCED BY
      AQUATIC PLANTS(1).
AB  - Several cyanobacterial species have a high potential to dominate in marine
      environments and freshwater reservoirs, and the ecological and physiological
      reasons for this phenomenon are not understood comprehensively. In this study,
      the ability of a Microcystis aeruginosa Kutz. strain to produce free dissolved
      enzymes was documented. We have observed that this highly toxic strain releases
      alkaline phosphatase, leucine aminopeptidase, and beta-glucosidase into the
      ambient environment. Additionally, the inhibitory activity of selected phenols
      produced by aquatic plants on the activity of these enzymes was analyzed. The
      investigated compounds, pyrogallol and, to a lesser degree, hydroquinone,
      decreased the activity of extracellular enzymes produced by M. aeruginosa, with
      leucine aminopeptidase being the most sensitive to the inhibitors. The
      noncompetitive character of enzymatic inhibition suggests that the polyphenols
      produced by aquatic plants are able to influence the activity of different
      extracellular or membrane-bound enzymes. 

PMID- 27032587
TI  - MICROSPECTROPHOTOMETRY AS A METHOD TO IDENTIFY KLEPTOPLASTIDS IN THE NAKED
      FRESHWATER DINOFLAGELLATE GYMNODINIUM ACIDOTUM(1).
AB  - A relatively small number of freshwater dinoflagellates are involved in symbiotic
      association with cryptophytes. The chloroplasts of the cryptophytes are retained
      by the dinoflagellate and give it the characteristic phycobilin pigmentation,
      either phycoerythrin or phycocyanin. The pigment characterization of the retained
      chloroplasts can give precise and accurate information about the type of
      cryptophyte preyed upon by the dinoflagellate. For this purpose, we performed
      microspectrophotometric evaluation of the pigments of Gymnodinium acidotum
      Nygaard and three different cryptophytes present in samples collected from a
      tributary of the river Arno, in Tuscany (Italy). The comparison of the different
      spectroscopic data allowed us to discriminate effectively among the cryptophytes
      preyed upon by the dinoflagellate. 

PMID- 27032588
TI  - IDENTIFICATION OF THE MINUS MATING-TYPE SPECIFIC GENE MTD1 FROM GONIUM PECTORALE
      (VOLVOCALES, CHLOROPHYTA)(1).
AB  - Gonium pectorale O. F. Mull. (Volvocales, Chlorophyta), a colonial 8- or 16
      cellular alga, is phylogenetically important as an intermediate form between
      isogametic unicellular Chlamydomonas and oogamous Volvox. We identified the
      mating-type specific gene GpMTD1, from G. pectorale, the first homologue of
      Chlamydomonas reinhardtii MTD1 (CrMTD1). The GpMTD1 gene was found to be present
      only in the minus mating-type locus and was expressed specifically in the gametic
      phase as is the case for CrMTD1, suggested to participate in development of the
      minus gametes. This gene is useful as a probe in analyzing the bacterial
      artificial chromosome (BAC) library for resolving genomic structures of the
      mating-type loci in isogamous and oogamous colonial volvocaleans. 

PMID- 27032589
TI  - GENETIC VARIATION AMONG STRAINS OF PSEUDOPFIESTERIA SHUMWAYAE AND PFIESTERIA
      PISCICIDA (DINOPHYCEAE)(1).
AB  - The putatively toxic dinoflagellates Pseudopfiesteria shumwayae (Glasgow et J. M.
      Burkh.) Litaker, Steid., P. L. Mason, Shields et P. A. Tester and Pfiesteria
      piscicida Steid. et J. M. Burkh. have been implicated in massive fish kills and
      of having negative impacts on human health along the mid-Atlantic seaboard of the
      USA. Considerable debate still remains as to the mechanisms responsible for fish
      mortality (toxicity vs. micropredation) caused by these dinoflagellates. Genetic
      differences among these cultures have not been adequately investigated and may
      account for or correlate with phenotypic variability among strains within each
      species. Genetic variation among strains of Ps. shumwayae and P. piscicida was
      examined by PCR-RFLP analysis using cultures obtained from the Provasoli-Guillard
      National Center for Culture of Marine Phytoplankton (CCMP), as well as those from
      our own and other colleagues' collection efforts. Examination of restriction
      digest banding profiles for 22 strains of Ps. shumwayae revealed the presence of
      10 polymorphic restriction endonuclease sites within the first and second
      internal transcribed spacers (ITS1 and ITS2) and the 5.8S gene of the rDNA
      complex, and the cytochrome oxidase subunit I (COI) gene. Three compound
      genotypes were represented within the 22 Ps. shumwayae strains. Conversely, PCR
      RFLP examination of 14 strains of P. piscicida at the same ITS1, 5.8S, and ITS2
      regions revealed only one variable restriction endonuclease site, located in the
      ITS1 region. In addition, a dinoflagellate culture listed as P. piscicida (CCMP
      1928) and analyzed as part of this study was identified as closely related to
      Luciella masanensis P. L. Mason, H. J. Jeong, Litaker, Reece et Steid. 

PMID- 27032590
TI  - MITOCHONDRIAL DNA IN THE OOGAMOCHLAMYS CLADE (CHLOROPHYCEAE): HIGH GC CONTENT AND
      UNIQUE GENOME ARCHITECTURE FOR GREEN ALGAE(1).
AB  - Most mitochondrial genomes in the green algal phylum Chlorophyta are AT-rich,
      circular-mapping DNA molecules. However, mitochondrial genomes from the
      Reinhardtii clade of the Chlorophyceae lineage are linear and sometimes
      fragmented into subgenomic forms. Moreover, Polytomella capuana, from the
      Reinhardtii clade, has an elevated GC content (57.2%). In the present study, we
      examined mitochondrial genome conformation and GC bias in the Oogamochlamys clade
      of the Chlorophyceae, which phylogenetic data suggest is closely related to the
      Reinhardtii clade. Total DNA from selected Oogamochlamys taxa, including four
      Lobochlamys culleus (H. Ettl) Proschold, B. Marin, U. G. Schloss. et Melkonian
      strains, Lobochlamys segnis (H. Ettl) Proschold, B. Marin, U. G. Schloss. et
      Melkonian, and Oogamochlamys gigantea (O. Dill) Proschold, B. Marin, U. G.
      Schloss. et Melkonian, was subjected to Southern blot analyses with cob and cox1
      probes, and the results suggest that the mitochondrial genome of these taxa is
      represented by multiple-sized linear DNA fragments with overlapping homologies.
      On the basis of these data, we propose that linear mitochondrial DNA with a
      propensity to become fragmented arose in an ancestor common to the Reinhardtii
      and Oogamochlamys clades or even earlier in the evolutionary history of the
      Chlorophyceae. Analyses of partial cob and cox1 sequences from these
      Oogamochlamys taxa revealed an unusually high GC content (49.9%-65.1%) and
      provided evidence for the accumulation of cob and cox1 pseudogenes and truncated
      sequences in the mitochondrial genome of all L. culleus strains examined. 

PMID- 27032591
TI  - MOLECULAR DIVERSITY OF MARINE PHYTOPLANKTON COMMUNITIES BASED ON KEY FUNCTIONAL
      GENES(1).
AB  - The phylogeny and diversity of two key functional genes were investigated as the
      basis for improved understanding of the community structure of natural
      phytoplankton assemblages in marine environments. New partial NR (encoding
      eukaryotic assimilatory nitrate reductase) and rbcL (encoding LSU of RUBISCO)
      sequences from 10 cultured phytoplankton strains are reported. Phytoplankton
      community composition from Monterey Bay (MB), a coastal upwelling site on the
      California coast, and the Western English Channel (EC), a North Atlantic spring
      bloom environment, was elucidated based on NR and rbcL sequences. Diatoms were by
      far the most frequently detected group in both environments, consistent with
      their importance as a major bloom-forming group. Both NR and rbcL libraries
      contained sequences representing cosmopolitan types such as Emiliania huxleyi
      (Lohmann) W. W. Hay et H. P. Mohler, Phaeocystis, and Pseudo-nitzschia. The NR
      and rbcL libraries also contained sequences from other chromophytic algal groups
      and the Dinophyceae (alveolates). Sequences showing identity with key bloom
      forming organisms including E. huxleyi, Phaeocystis pouchetii (Har.) Lagerh.,
      Pseudo-nitzschia sp., and Thalassiosira sp. in the rbcL libraries confirm
      previous studies from these environments based on traditional approaches.
      Diversity/pattern analyses detected significant compositional differences among
      the libraries, which were consistent with patterns identified by phylogenetic
      analysis, but these patterns were not strongly correlated with obvious
      environmental variables such as temperature and nitrate concentration. Many new
      and divergent NR and rbcL sequences are reported, but the extent to which they
      represent unknown types cannot be determined until greater effort is made to
      sequence the existing culture collections. 

PMID- 27032592
TI  - DIVERSITY AND MORPHOLOGY OF SKELETONEMA SPECIES IN SOUTHERN BRAZIL, SOUTHWESTERN
      ATLANTIC OCEAN(1).
AB  - We examined the morphology of Skeletonema species occurring in coastal waters of
      southern Brazil, on the basis of LM, SEM, and TEM analyses of six isolated
      strains and of 13 field samples from the Patos Lagoon estuary and the adjacent
      Cassino Beach. We concluded that the genus Skeletonema is highly diverse in
      coastal waters of southern Brazil, with the occurrence of four confirmed species:
      S. costatum, S. pseudocostatum, S. potamos, and S. tropicum. In addition, EM
      details must still be provided for S. menzelii, and genetic studies should be
      conducted to confirm the identity of S. cf. grethae and S. subsalsum. The high
      diversity in this geographic area can be attributed to the proximity of the
      Subtropical Convergence and to the freshwater ecosystems of Patos Lagoon and La
      Plata River that favor the presence of warm-, cold-, and brackish-water species. 

PMID- 27032593
TI  - MICROMORPHOGENESIS DURING DIATOM WALL FORMATION PRODUCES SILICEOUS NANOSTRUCTURES
      WITH DIFFERENT PROPERTIES(1).
AB  - Micromorphogenesis within the silica deposition vesicle (SDV) of the diatom
      Pinnularia viridis (Nitzsh) Ehrenb. resulted in distinct silica nanostructures
      and layers within forming valves and girdle bands. These siliceous components
      were similarly disclosed following alkaline etching of mature valves/girdle
      bands, where their different susceptibilities to dissolution over time resulted
      from apparent differences in silica density and/or chemistry. The bulk of silica
      appeared to be deposited at the interface of the forming valve or girdle band
      with the silicalemma and occurred by the outward expansion of microfibrils of
      silica that aligned perpendicularly to the silicalemma. Microfibrils originated
      from both sides of the "silica lamella," the first nanostructure formed within
      the SDV, and several silica species of distinct nanostructure and density
      resulted, including distinctive inner and outermost silica "coverings" of mature
      valves/girdle bands and the central and terminal nodules. Not all silica
      deposition and micromorphogenesis occurred in contact with the expanding
      silicalemma, but was somehow directed within the SDV cavity, and resulted in the
      distinct silica layers that lined the raphe fissures and poroids. Following
      alkaline etching, the inner surfaces of valves/girdle bands, as well as the
      silica layers lining the raphes, poroids, and slits, were determined to be
      significantly more resistant to alkaline etching than the exterior surfaces,
      while the outer silica coating and the nodules were quickly dissolved. The
      processes of micromorphogenesis must have exerted precise control over the
      chemical nature of the silica formed at different positions within the SDV and
      affected the overall structure and function of the diatom wall. 

PMID- 27032594
TI  - POLYPHASIC CHARACTERIZATION OF THREE STRAINS OF ANABAENA RENIFORMIS AND
      APHANIZOMENON APHANIZOMENOIDES (CYANOBACTERIA) AND THEIR RECLASSIFICATION TO
      SPHAEROSPERMUM GEN. NOV. (INCL. ANABAENA KISSELEVIANA)(1).
AB  - Occurrences of rare cyanobacteria Anabaena reniformis Lemmerm. and Aphanizomenon
      aphanizomenoides (Forti) Horecka et Komarek were recently detected at several
      localities in the Czech Republic. Two monoclonal strains of An. reniformis and
      one strain of Aph. aphanizomenoides were isolated from distant localities and
      different sampling years. They were characterized by a combination of
      morphological, genetic, and biochemical approaches. For the first time, partial
      16S rRNA gene sequences were obtained for these morphospecies. Based on this
      gene, all of these strains clustered separately from other planktonic Anabaena
      and Aphanizomenon strains. They appeared in a cluster with Cylindrospermopsis
      Seenaya et Subba Raju and Raphidiopsis F. E. Fritsch et M. F. Rich, clustered
      closely together with two An. kisseleviana Elenkin strains available from
      GenBank. A new generic entity was defined (Sphaerospermum gen. nov., with the
      type species S. reniforme, based on the traditional species An. reniformis).
      These results contribute significantly to the knowledge base about genetic
      heterogeneity among planktonic Anabaena-like and Aphanizomenon-like
      morphospecies. Accordingly, the subgenus Dolichospermum, previously proposed for
      the group of planktonic Anabaena, should be revaluated. Secondary metabolite
      profiles of the An. reniformis and Aph. aphanizomenoides strains differed
      considerably from 17 other planktonic Anabaena strains of eight morphospecies
      isolated from Czech water bodies. Production of puwainaphycin A was found in both
      of the An. reniformis strains. Despite the relatively short phylogenetic distance
      from Cylidrospermopsis, the production of cylindrospermopsin was not detected in
      any of our strains. 

PMID- 27032595
TI  - TAXONOMIC REVISION OF SARGASSUM SPECIES (FUCALES, PHAEOPHYCEAE) FROM NEW
      CALEDONIA BASED ON MORPHOLOGICAL AND MOLECULAR ANALYSES(1).
AB  - Sargassum C. Agardh (1820) is a taxonomically difficult genus distributed
      worldwide and reported as the most species-rich genus of the Fucales. It is
      especially abundant in the Pacific where decreasing species richness is reported
      to occur from west to east. New Caledonia has been recognized as one of the
      hotspots of Sargassum diversity; however, species lists available for this region
      are old and incomplete and have not yet been updated with regard to the latest
      taxonomic revisions published. This study aimed at revising Sargassum diversity
      in New Caledonia and to assess its geographic affinities with neighboring Pacific
      regions. We used combined morphological and DNA analyses on new collections and
      examined numerous type specimens. Although 45 taxa have been listed in the
      literature, most of them have been either transferred to synonymy since or
      misidentified, and in this study, only 12 taxa were recognized as occurring in
      New Caledonia. They belong to the subgenus Sargassum sect. Binderianae (Grunow)
      Mattio et Payri (2), sect. Ilicifoliae (J. Agardh) Mattio et Payri (2), sect.
      Polycystae Mattio et Payri. (1), sect. Sargassum (4), sect. Zygocarpicae (J.
      Agardh) Setch. (2), and subgenus Phyllotrichia (Aresh.) J. Agardh (1). New
      Caledonian Sargassum flora appeared as the second richest in the region after the
      Pacific coast of Australia, with which it has shown high similarity, and shared
      species with all neighboring regions. One species, S. turbinarioides Grunow, is
      considered as endemic to New Caledonia. The low genetic diversity detected among
      several polymorphic species belonging to sect. Sargassum is also discussed. 

PMID- 27032596
TI  - AN EXAMINATION OF PACHYMENIA AND AEODES (HALYMENIACEAE, RHODOPHYTA) IN NEW
      ZEALAND AND THE TRANSFER OF TWO SPECIES OF AEODES IN SOUTH AFRICA TO
      PACHYMENIA(1).
AB  - A phylogenetic study was conducted of species of Halymeniaceae from New Zealand
      presently placed in Aeodes or Pachymenia, based on maximum-likelihood (ML),
      maximum-parsimony (MP), and Bayesian analyses of rbcL and nuclear internal
      transcribed spacer (ITS) rDNA sequences. We used molecular and morphological data
      in combination with exhaustive sampling of herbarium collections to clarify the
      taxonomy and distributions of New Zealand members of Pachymenia and Aeodes. Our
      study confirms the presence of three erect species of Pachymenia on the New
      Zealand mainland, and we resurrect the name Pachymenia dichotoma J. Agardh for
      the widely distributed, southernmost species. Species of Aeodes from South Africa
      are shown to be closely related to Pachymenia carnosa (J. Agardh) J. Agardh, the
      type species of Pachymenia, and are accordingly transferred to Pachymenia. 

PMID- 27032597
TI  - LOCALIZATION OF MICROCYSTIN SYNTHETASE GENES IN COLONIES OF THE CYANOBACTERIUM
      MICROCYSTIS USING FLUORESCENCE IN SITU HYBRIDIZATION(1).
AB  - To better understand the production of microcystins (MCs) in Microcystis
      colonies, fluorescence in situ hybridization (FISH) methods were developed to
      detect DNA involved in the synthesis of these cyanobacterial hepatotoxins. Using
      colonies of Microcystis aeruginosa (Kutz.) Kutz. isolated from environmental
      blooms of cyanobacteria and from a colony-forming, MC-producing laboratory strain
      of Microcystis, amplified PCR products were observed, coincident with positive
      controls. The total MC content of individual colonies of Microcystis, determined
      by ELISA, showed a positive correlation with colony cross-sectional area. FISH
      analysis of Microcystis colonies gave high fluorescence in comparison to negative
      controls, indicating the presence of MC synthetase DNA (mcyA) in situ. FISH
      analysis for MC synthetase genes has the potential to be developed into an
      effective early warning tool for drinking and recreational water management. 

PMID- 27032599
TI  - JOURNAL OF PHYCOLOGY REVIEWERS.

PMID- 27032598
TI  - OPTIMAL GROWTH CONDITIONS AND ANTIOXIDATIVE ACTIVITIES OF CYLINDROTHECA
      CLOSTERIUM (BACILLARIOPHYCEAE)(1).
AB  - We isolated the unialgal strain of Cylindotheca closterium (Ehrenb.) Reimann et
      J. C. Lewin and produced an axenic strain using an antibiotic cocktail of
      enriched f/2 artificial seawater medium. The optimal growth conditions were
      estimated under 27 different combinations of temperature, salinity, and
      nutrients, and mass culture was performed based on the best specific growth
      conditions. Its antioxidant activities were determined from the extracts of
      methanol, water, and enzymes (proteases and carbohydrases). The maximum specific
      growth rate (MUmax ) varied from 0.63 to 0.97 . d(-1) . The maximum cell density
      was 7.20 * 10(4) cells . mL(-1) , while the MUmax was 0.82 . d(-1) in culture
      conditions of 20 degrees C, 30 psu (practical salinity unit), and "F" nutrient
      concentrations on day 10 of the culture period. The scavenging rates for 1,1
      diphenyl-2-picrylhydrazyl (DPPH) free radical were 72.5% and 69.4% from Viscozyme
      and methanol extracts, respectively. The enzymatic extracts of C. closterium
      prepared by the hydrolyses of Amyloglucosidase (AMG) and Viscozyme showed 45.8%
      and 45.5% nitric-oxide-scavenging rates, slightly lower than the activity of
      alpha-tocopherol (alpha-tocopherol) but similar to butylated hydroxytoluene
      (BHT). The extract from methanol and water showed 44.8% and 44.4% scavenging
      rates, statistically similar with BHT. The metal-chelating activities of the
      Kojizyme, Alcalase, methanol, Viscozyme, and Neutrase extracts were 67.1, 53.9,
      53.2, 52.1, and 50.2 %, respectively, five to six times higher than the
      commercial antioxidants. The AMG, Viscozyme, and Neutrase extracts showed a
      remarkable linoleic acid peroxidation inhibition, which was higher than BHT and
      statistically similar with alpha-tocopherol. 

PMID- 27032600
TI  - Ghostbusting-Taking the sheet off the ghost.

PMID- 27032601
TI  - Proliferation and Differentiation Deficits are a Major Convergence Point for
      Neurodevelopmental Disorders.
AB  - Several lines of evidence suggest that proliferation and differentiation in
      neural stem cells (NSCs) are a major convergence point of neurodevelopmental
      disorders (NDDs). Most genes with truncating mutations are implicated in NSC
      proliferation and differentiation (e.g., MBD5, CDKL5, and MECP2). Similarly,
      reciprocal deletion/duplication copy-number variants (CNVs), such as 1q21.1 and
      16p11.2, are inversely correlated with head size. In addition, pathways such as
      MAPK, mTOR, and RAS, which are important in cancer, a disease of uncontrolled
      cell proliferation, are implicated in NDDs. These deficits are a measurable
      output of patient-derived induced neural progenitor cells, and may represent a
      diagnostic tool and a possible clinical intervention point for molecular
      therapies, irrespective of genotype.

PMID- 27032602
TI  - A novel siglec (CgSiglec-1) from the Pacific oyster (Crassostrea gigas) with
      broad recognition spectrum and inhibitory activity to apoptosis, phagocytosis and
      cytokine release.
AB  - Sialic acid binding immunoglobulin-type lectin (siglec) belongs to the
      immunoglobulin superfamily (IgSF), which acts as regulator involved in glycan
      recognition and signal transduction in the immune and nervous systems. In the
      present study, a siglec gene (designated CgSiglec-1) was characterized from the
      Pacific oyster, Crassostrea gigas. The cDNA of CgSiglec-1 was of 1251 bp encoding
      a predicted polypeptide of 416 amino acids. CgSiglec-1 was composed of two I-set
      immunoglobulin (Ig) domains, one transmembrane (TM) domain and two ITIM motifs,
      sharing a sequence similarity with vertebrate CD22 homologs. The mRNA expression
      of CgSiglec-1 could be detected in all the selected tissues, with the highest
      level in hemocytes and labial palps. The confocal analysis revealed that CgSiglec
      1 mainly distributed on the cytoplasmic membrane of the oyster hemocytes. In
      addition, the mRNA transcripts of CgSiglec-1 in hemocytes increased significantly
      (4.29-fold to that of control group, p < 0.05) after Vibrio splendidus
      stimulation. The recombinant CgSiglec-1 protein (rCgSiglec-1) could bind to poly
      sialic acid (pSIAS), lipopolysaccharides (LPS) and peptidoglycan (PGN) in a dose
      dependent manner. The blockade of CgSiglec-1 by specific polyclonal antibodies
      could enhance the LPS-induced cell apoptosis, phagocytosis towards V. splendidus
      and the release of cytokines, such as CgTNF-1, CgIFNLP and CgIL-17. The results
      collectively indicated that CgSiglec-1 could act as a bridge molecule between
      invader recognition and signal transduction cascade, and modulate the immune
      response by inhibiting various important processes of immunity in oyster.

PMID- 27032603
TI  - Medial Patellofemoral Ligament Reconstruction Combined With Bony Procedures for
      Patellar Instability: Current Indications, Outcomes, and Complications.
AB  - PURPOSE: The aim of this literature review is to analyze current indications,
      outcomes, and complication rates of medial patellofemoral ligament (MPFL)
      reconstruction associated with bony procedures in order to clarify efficacy and
      adoptability in selected patients with patellar instability. METHODS: A
      systematic review of the literature was performed following the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A
      search on PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases
      was performed, using various combinations of the keywords patellar instability,
      MPFL reconstruction, tibial tubercle osteotomy, and trochleoplasty. RESULTS:
      Fourteen of 501 articles were included. Indications for surgery included
      dysplasia and malalignment. All studies reported significant improvements in
      overall clinical outcomes. The most frequently used score was the Kujala score,
      with a mean value of 83.26. Functional failures ranged from 0% to 8.8%. Major
      complications were not described. Minor complications ranged from 0% to 40%.
      Reoperations ranged from 4.5% to 17.7%. CONCLUSIONS: A combined approach seems
      indicated in patients with patellar instability, especially among those with high
      tibial tuberosity-trochlear groove or severe trochlea dysplasia. Indications for
      combined MPFL and bony procedure are influenced by anatomy, including dysplasia
      and malalignment. We are unable to identify an absolute indication. Bony
      procedures are associated with increased morbidity. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level I to IV studies.

PMID- 27032604
TI  - Quality and Variability of Online Available Physical Therapy Protocols From
      Academic Orthopaedic Surgery Programs for Anterior Cruciate Ligament
      Reconstruction.
AB  - PURPOSE: To assess the quality and variability found across anterior cruciate
      ligament (ACL) rehabilitation protocols published online by academic orthopaedic
      programs. METHODS: Web-based ACL physical therapy protocols from United States
      academic orthopaedic programs available online were included for review. Main
      exclusion criteria included concomitant meniscus repair, protocols aimed at
      pediatric patients, and failure to provide time points for the commencement or
      recommended completion of any protocol components. A comprehensive, custom
      scoring rubric was created that was used to assess each protocol for the presence
      or absence of various rehabilitation components, as well as when those activities
      were allowed to be initiated in each protocol. RESULTS: Forty-two protocols were
      included for review from 155 U.S. academic orthopaedic programs. Only 13
      protocols (31%) recommended a prehabilitation program. Five protocols (12%)
      recommended continuous passive motion postoperatively. Eleven protocols (26%)
      recommended routine partial or non-weight bearing immediately postoperatively.
      Ten protocols (24%) mentioned utilization of a secondary/functional brace. There
      was considerable variation in range of desired full-weight-bearing initiation (9
      weeks), as well as in the types of strength and proprioception exercises
      specifically recommended. Only 8 different protocols (19%) recommended return to
      sport after achieving certain strength and activity criteria. CONCLUSIONS: Many
      ACL rehabilitation protocols recommend treatment modalities not supported by
      current reports. Moreover, high variability in the composition and time ranges of
      rehabilitation components may lead to confusion among patients and therapists.
      LEVEL OF EVIDENCE: Level II.

PMID- 27032605
TI  - Nonanatomic Tibial Tunnel Placement for Single-Bundle Posterior Cruciate Ligament
      Reconstruction Leads to Greater Posterior Tibial Translation in a Biomechanical
      Model.
AB  - PURPOSE: To determine the effect of varying proximal-distal tibial tunnel
      placement on posterior cruciate ligament (PCL) laxity. METHODS: Nine matched
      pairs (18 total) of cadaveric knees (mean age 79.3 years, range 60 to 89), were
      studied. The specimens from each pair were randomly divided into 2 groups based
      on tibial tunnel placement: (1) anatomic tunnel and (2) proximal nonanatomic
      tunnel. A 150-N cyclic posterior tibial load was applied using a Materials
      Testing System machine at 0 degrees , 30 degrees , 60 degrees , and 90 degrees 
      of knee flexion. Each specimen completed 50 cycles at a rate of 0.2 Hz at each
      knee flexion angle. In 10 specimens, a static 250-N posterior tibial load was
      applied at 90 degrees  of knee flexion. Posterior tibial translation was
      recorded. Load to failure for all specimens was recorded. RESULTS: With
      application of a 150-N posteriorly directed cyclic force, the anatomic tunnel
      group had significantly less posterior tibial translation (millimeters, mean
      [standard deviation (SD)]) than the proximal nonanatomic tunnel group at 0
      degrees , 30 degrees , 60 degrees , and 90 degrees  of knee flexion: 1.1 (0.3) v
      1.5 (0.4), P = .031; 1.1 (0.6) v 2.2 (0.9), P = .019; 0.9 (0.4) v 2.0 (0.6), P =
      .001; 0.9 (0.6) v 2.9 (0.7), P < .001, respectively. The anatomic tunnel group
      also demonstrated significantly less posterior tibial translation (millimeters,
      mean [SD]) than the nonanatomic tunnel group at 90 degrees  with a static 250-N
      posteriorly directed force applied (P <.05): 2.3 (1.3) v 6.1 (2.3), P = .016.
      Four pairs were excluded from the 250-N results because of prior load to failure
      testing. CONCLUSIONS: Anatomic tibial tunnel placement re-creating the tibial
      origin of the PCL results in significantly less posterior tibial translation than
      proximal nonanatomic tibial tunnel placement. Correct placement of the tibial
      tunnel during PCL reconstruction is essential for avoidance of posterior laxity.
      CLINICAL RELEVANCE: Anatomic tibial tunnel placement during PCL reconstruction
      may ensure a more stable reconstruction.

PMID- 27032606
TI  - Desmosomes and corneodesmosomes are enclosed by tight junctions at the periphery
      of granular cells and corneocytes, suggesting a role in generation of a
      peripheral distribution of corneodesmosomes in corneocytes.

PMID- 27032607
TI  - Television viewing and alcohol advertising with alcohol expectancies among school
      aged children in Taiwan.
AB  - OBJECTIVES: This study is aimed to examine the strength of association between
      television watching and potential exposure to alcohol advertising with
      multidimensional alcohol expectancies in school-aged children. METHODS: A total
      of 779 4th (age 10) and 768 6th (age 12) grade students were recruited from 17
      public elementary schools in northern Taiwan in 2006, with two waves of follow-up
      at 6 months apart. Self-administered questionnaires were used to collect
      information concerning individual characteristics, parental attributes, past-week
      screen time, drinking behaviors, and alcohol expectancies. Data of aired alcohol
      advertisements at baseline were obtained from the Nielsen Media Research
      Advertising Information Services; parenting styles were ascertained from the 1st
      follow-up. Alcohol Expectancies Questionnaire-Children version was used to
      measure alcohol expectancies (AEs) at baseline and the 2nd follow-up. RESULTS:
      Nearly 27% of students reported watching television for more than two hours per
      day and 58% watching television after 9 p.m. Dimension-related heterogeneity
      exists in the relationship between TV viewing and alcohol advertising with AEs.
      With statistical adjustment for covariates, spending more than two hours watching
      TV per day was associated with increased levels of positive AEs "Promoting
      Relaxation or Tension Reduction [PRTR]" (beta=1.52, 95% CI=0.92, 2.12; p<0.001);
      the exposure to alcohol advertising was associated with decline in negative AEs
      "Deteriorated Cognitive and Behavioral Function" (e.g., >8.0 ads: beta=-1.06, 95%
      CI=-1.66, -0.47, p<0.01). CONCLUSIONS: Greater screen time is associated with
      elevated positive expectancies of PRTR and alcohol advertising exposure is linked
      with lowered negative expectancies in late childhood. School-based anti-underage
      drinking programs may consider integrating the media literacy curriculum.

PMID- 27032608
TI  - Fluoroscopic balloon dilatation for anastomotic strictures in patients with
      esophageal atresia: A fifteen-year single centre UK experience.
AB  - AIM OF THE STUDY: To assess the safety and effectiveness of fluoroscopic balloon
      dilatation (FBD) in children with esophageal anastomotic stricture after surgical
      repair of esophageal atresia. METHODS: All patients undergoing surgery for
      esophageal atresia and requiring dilatation(s) during a consecutive 15-year
      period [April 2000-September 2014] were analyzed. Dilatations were performed as
      day case procedures under general anesthesia using a radial force generating
      balloon device (Boston Scientific Corporation) by surgeons. Outcomes assessed
      included - (1) the number of dilatations/patient, (2) effectiveness and (3) need
      for surgery and (4) complications. RESULTS: One hundred thirty seven patients
      underwent 625 FBD sessions (median 3 dilations per patient; range 1-24
      dilatations). Median age at 1st FBD was 0.74years (range 0.05-16.1years). Balloon
      catheter sizes ranged from 6mm to 20mm. FBD yielded excellent results in 99
      patients (74%), while 17 cases (13%) had mild ongoing dysphagia/dysmotility. Ten
      patients (7%) required further dilatation(s) to control symptoms. No patient(s)
      required esophageal stenting. Five cases required G-tube feeds as a result of
      oral aversion behavior - all of these cases were complex/VACTERL patients. Only 1
      minor radiological leak occurred after a dilatation session and this did not
      require surgical intervention. A single patient (long gap EA TEF) with severe
      neurological impairment having multiple dilatations and stricture resection
      ultimately required esophageal replacement. Anti-reflux surgery was performed in
      36 patients (26%) for medical therapy resistant GER. CONCLUSION: FBD for
      anastomotic stricture(s) following esophageal atresia repair achieved very good
      outcomes for the majority of EA TEF patients. The procedure can be accomplished
      safely as indicated by the low complication rate herein reported. Although some
      children may require more than one dilatation session prompt relief of symptoms
      can be achieved with a vigilant care program co-ordinated by a multidisciplinary
      specialist EA TEF team.

PMID- 27032609
TI  - Harvesting the benefits of biofilms: A novel probiotic delivery system for the
      prevention of necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: Probiotics reduce the incidence of necrotizing enterocolitis
      (NEC) albeit only when administered at high frequency (at least daily). We have
      developed a novel probiotic delivery system in which probiotics are grown as a
      biofilm on microspheres, allowing enhanced efficacy with only a single treatment.
      METHODS: Neonatal rats were subjected to experimental NEC. Pups received a single
      enteral dose of: (1) vehicle only, (2) unloaded microspheres, (3) MRS (broth)
      loaded microspheres, (4) Lactobacillus reuteri, (5) L. reuteri grown on unloaded
      microspheres, or (6) L. reuteri grown on MRS-loaded microspheres. Intestinal
      injury was graded histologically and intestinal permeability determined by serum
      levels of enterally administered fluorescein isothiocyanate-labeled dextran.
      RESULTS: 69% of untreated pups developed NEC, whereas 32% of pups treated with L.
      reuteri grown as a biofilm on unloaded microspheres (p=0.009) and 33% of pups
      treated with L. reuteri grown as a biofilm on MRS-loaded microspheres (p=0.005)
      developed NEC. No other group had a significant reduction in NEC. Furthermore,
      pups treated with L. reuteri grown as a biofilm had significantly reduced
      intestinal permeability. CONCLUSIONS: A single dose of Lactobacillus biofilm
      grown on biocompatible microspheres significantly reduces NEC incidence and
      severity. This novel probiotic delivery system may be beneficial in the
      prevention of NEC in the future.

PMID- 27032610
TI  - Gastroschisis: Bellwether for neonatal surgery capacity in low resource settings?
AB  - INTRODUCTION: Economic disadvantage may adversely influence the outcomes of
      infants with gastroschisis (GS). Gastroschisis International (GiT) is a network
      of seven paediatric surgical centres, spanning two continents, evaluating GS
      treatment and outcomes. MATERIAL AND METHODS: A 2-year retrospective review of GS
      infants at GiT centres. Primary outcome was mortality. Sites were classified into
      high, middle and low income country (HIC, MIC, and LIC). MIC and LIC were
      sometimes combined for analysis (LMIC). Disability adjusted life years (DALYs)
      were calculated and centres with the highest mortality underwent a needs
      assessment. RESULTS: Mortality was higher in the LICs and LMICs: 100% in Uganda
      and Cote d'Ivoire, 75% in Nigeria and 60% in Malawi. 29% and 0% mortality was
      reported in South Africa and the UK, respectively. Septicaemia was the commonest
      cause of death. Averted and non-avertable DALYs were nil in Uganda and Cote
      d'Ivoire (no survivors). In the UK (100% survival) averted DALYs (met need) was
      highest, representing death and disability prevented by surgical intervention.
      Performance improvement measures were agreed: a prospectively maintained GS
      register; clarification of the key team members of a GS team and management
      pathway. CONCLUSIONS: We propose the use of GS as a bellwether condition for
      assessing institutional capacity to deliver newborn surgical care. Early access
      to care, efficient multidisciplinary team working, appropriate resuscitation,
      avoidance of abdominal compartment syndrome, stabilization prior to formal
      closure and proactive nutritional interventions may reduce GS-associated burden
      of disease in low resource settings.

PMID- 27032611
TI  - Trends in treatment of infectious parapneumonic effusions in U.S. children's
      hospitals, 2004-2014.
AB  - PURPOSE: The purpose of this study was to examine trends in the treatment of
      patients with infectious parapneumonic effusions in U.S. children's hospitals
      over the past decade. METHODS: The PHIS database was queried for patients younger
      than 18years old with pneumonia and pleural effusion in three yearlong periods
      over the past decade. Variables included age, gender, payer, race/ethnicity,
      hospital region, hospital type, markers of illness severity, and treatment group
      (antibiotics alone, chest tube thoracostomy+/-thrombolytics, video-assisted
      thoracoscopy (VATS), or thoracotomy). RESULTS: 5569 patients were included in the
      final analysis. The proportion of patients treated with antibiotics alone
      increased from 62% to 74% from 2004 to 2014 (p<0.001). Among patients requiring
      pleural space drainage, the frequency of VATS peaked in 2009 (50.8%), dropping to
      36.4% in 2014 (p<0.001), while tube thoracostomy, usually with fibrinolytics,
      rose from 39.0% in 2009 to 53.2% in 2014 (p<0.001). CONCLUSION: In a select
      cohort of free-standing, tertiary care U.S. children's hospitals, antibiotic
      administration alone remains the most common treatment approach to infectious
      parapneumonic effusions. VATS treatment for those patients requiring pleural
      space drainage is being gradually supplanted by thoracostomy tube placement with
      instillation of fibrinolytics.

PMID- 27032612
TI  - Vector serotype screening for use in ovine perinatal lung gene therapy.
AB  - PURPOSE: Successful in utero or perinatal gene therapy for congenital lung
      diseases, such as cystic fibrosis and surfactant protein deficiency, requires
      identifying clinically relevant viral vectors that efficiently transduce airway
      epithelial cells. The purpose of the current preclinical large animal study was
      to evaluate lung epithelium transduction of adeno-associated viral (AAV) vector
      serotypes following intratracheal delivery. METHODS: Six different AAV vector
      serotypes (AAV1, AAV5, AAV6, AAV8, AAV9, and AAVrh10) expressing the green
      fluorescent protein (GFP) as the transgene were injected into the right upper
      lobe of perinatal sheep via bronchoscopy. At 1 week, samples were harvested,
      analyzed by fluorescent stereomicroscopy and immunohistochemistry, and quantified
      using a radial grid and quantitative real-time polymerase chain reaction (qPCR).
      RESULTS: Fluorescent stereomicroscopy demonstrated GFP expression in the right
      upper lobe following injection of all AAV serotypes assessed except AAV5.
      Immunohistochemistry analysis confirmed GFP expression in small- and medium-sized
      airways following intratracheal injection of AAV1, 6, 8, 9, and rh10. However,
      only AAV8 and AAVrh10 resulted in transgene expression in large airways. These
      results were confirmed by qPCR, yet, after 40 cycles, AAV1 did not show GFP gene
      amplification. CONCLUSION: Adeno-associated viral vector serotypes 6, 8, 9, and
      rh10 demonstrated efficient GFP transgene expression at early time points, and
      AAV8 demonstrated efficient transduction of all airway sizes with high pulmonary
      GFP expression tested using qPCR.

PMID- 27032613
TI  - Tumor risk of children with 45,X/46,XY gonadal dysgenesis in relation to their
      clinical presentations: Further insights into the gonadal management.
AB  - OBJECTIVE: To investigate the risk of gonadal germ cell neoplasms (GCN) in
      children with 45,X/46,XY gonadal dysgenesis and its relation to the clinical
      presentations. METHODS: We conducted a retrospective study reviewing the clinical
      and gonadal features of all consecutive children with 45,X/46,XY gonadal
      dysgenesis who received gonadal management in a tertiary center from 1985 to
      2015. Study subjects were divided into Group I(significant genitalia anomaly),
      Group II(female phenotype) and Group III(male phenotype). RESULTS: 21 children
      were studied (Group I=8; Group II=11; Group III=2). All 19 children of Group I
      and II eventually underwent bilateral gonadectomy. One patient of Group III
      underwent gonadal biopsy which showed increase in fibrous tissue in the testes
      without any GCN. 3/8(37.5%) and 6/11(54.5%) of patients in Group I and II
      respectively had either gonadoblastoma (GB) or carcinoma-in-situ (CIS) or both
      affecting one or both gonads. Among Group I patients, the 4 dysgenetic testes
      affected by CIS in 3 patients were intraabdominal (n=1), inguinal (n=1) and
      scrotal (n=2) in positions. Among Group II patients, 6/20 streak gonads had GB
      and 2/2 dysgenetic testes had GB or CIS. CONCLUSIONS: 45,X/46,XY children with
      significant genitalia anomaly or female phenotype are both at high risk of
      gonadal GCN.

PMID- 27032614
TI  - Suction rectal biopsy yields adequate tissue in children.
AB  - BACKGROUND/PURPOSE: Hirschsprung disease (HD) is diagnosed by rectal biopsy, with
      suction rectal biopsy (SRB), the preferred technique in neonates. Reported SRB
      adequacy has varied overall with concern for decreased diagnostic yield in older
      children. The study aim was to assess SRB adequacy by age in children with the
      current device used at our institution. METHODS: Following IRB approval, a
      retrospective cohort of children (1 to 18years) evaluated by SRB for HD was
      identified through billing records. Data regarding demographics, procedure,
      results, and complications were collected and analyzed using SPSS. RESULTS: 56
      children (median age 3.9years) underwent SRB with an 80.4% overall success rate.
      Patients older than 5years had 90.5% adequacy rate compared to 74.3% in those
      younger. Univariate analysis revealed weak association of inadequate specimens
      with younger age and males, and no association with insurance, race/ethnicity,
      weight-height or BMI percentile, sedation type, or procedure location. SRB under
      general anesthesia (GA) had 100% adequacy (n=6). Patients with inadequate initial
      biopsy achieved diagnosis by SRB with increased sedation (n=5) or full thickness
      biopsy under GA (n=5). CONCLUSION: With adequacy of 80.4% overall and 90.5% for
      patients greater than 5years, SRB is effective in evaluating the older child for
      HD.

PMID- 27032615
TI  - Fluorescently labeled bacteria provide insight on post-mortem microbial
      transmigration.
AB  - Microbially mediated mechanisms of human decomposition begin immediately after
      death, and are a driving force for the conversion of a once living organism to a
      resource of energy and nutrients. Little is known about post-mortem microbiology
      in cadavers, particularly the community structure of microflora residing within
      the cadaver and the dynamics of these communities during decomposition. Recent
      work suggests these bacterial communities undergo taxa turnover and shifts in
      community composition throughout the post-mortem interval. In this paper we
      describe how the microbiome of a living host changes and transmigrates within the
      body after death thus linking the microbiome of a living individual to post
      mortem microbiome changes. These differences in the human post-mortem from the
      ante-mortem microbiome have demonstrated promise as evidence in death
      investigations. We investigated the post-mortem structure and function dynamics
      of Staphylococcus aureus and Clostridium perfringens after intranasal inoculation
      in the animal model Mus musculus L. (mouse) to identify how transmigration of
      bacterial species can potentially aid in post-mortem interval estimations. S.
      aureus was tracked using in vivo and in vitro imaging to determine colonization
      routes associated with different physiological events of host decomposition,
      while C. perfringens was tracked using culture-based techniques. Samples were
      collected at discrete time intervals associated with various physiological events
      and host decomposition beginning at 1h and ending at 60 days post-mortem. Results
      suggest that S. aureus reaches its highest concentration at 5-7 days post-mortem
      then begins to rapidly decrease and is undetectable by culture on day 30. The
      ability to track these organisms as they move in to once considered sterile space
      may be useful for sampling during autopsy to aid in determining post-mortem
      interval range estimations, cause of death, and origins associated with the
      geographic location of human remains during death investigations.

PMID- 27032617
TI  - Rearing Mozambique tilapia in tidally-changing salinities: Effects on growth and
      the growth hormone/insulin-like growth factor I axis.
AB  - The growth hormone (GH)/insulin-like growth factor (IGF) axis plays a central
      role in the regulation of growth in teleosts and has been shown to be affected by
      acclimation salinity. This study was aimed at characterizing the effects of
      rearing tilapia, Oreochromis mossambicus, in a tidally-changing salinity on the
      GH/IGF axis and growth. Tilapia were raised in fresh water (FW), seawater (SW),
      or in a tidally-changing environment, in which salinity is switched between FW
      (TF) and SW (TS) every 6h, for 4months. Growth was measured over all time points
      recorded and fish reared in a tidally-changing environment grew significantly
      faster than other groups. The levels of circulating growth hormone (GH), insulin
      like growth factor I (IGF-I), pituitary GH mRNA, gene expression of IGF-I, IGF
      II, and growth hormone receptor 2 (GHR) in the muscle and liver were also
      determined. Plasma IGF-I was higher in FW and TS than in SW and TF tilapia.
      Pituitary GH mRNA was higher in TF and TS than in FW and SW tilapia. Gene
      expression of IGF-I in the liver and of GHR in both the muscle and liver changed
      between TF and TS fish. Fish growth was positively correlated with GH mRNA
      expression in the pituitary, and GHR mRNA expression in muscle and liver tissues.
      Our study indicates that rearing fish under tidally-changing salinities elicits a
      distinct pattern of endocrine regulation from that observed in fish reared in
      steady-state conditions, and may provide a new approach to increase tilapia
      growth rate and study the regulation of growth in euryhaline fish.

PMID- 27032616
TI  - Signaling by Cellular Protrusions: Keeping the Conversation Private.
AB  - Information exchange between different cells makes multicellular life possible.
      Signaling between cells can occur over long distances, as in the case of hormone
      signaling, or it can take place over short distances between immediately
      juxtaposed neighbors, as in the case of stem cell-niche signaling. The ability of
      signal-sending and -receiving cells to communicate with one another in a specific
      manner is of paramount importance in the proper development and function of
      tissues. Growing evidence indicates that different cellular protrusions help to
      achieve specificity in signaling that occurs between distinct cell types. Here,
      we focus on new roles for cellular protrusions in cell-to-cell communication,
      drawing special attention to how stem cells use specialized extensions to promote
      reception of self-renewing signals emanating from the niche.

PMID- 27032618
TI  - Anatomic cadaveric study of the extensile extensor digitorum communis splitting
      approach for exposing the ulnar coronoid process.
AB  - BACKGROUND: The extensile extensor digitorum communis (EDC) splitting approach
      can access the ulnar coronoid process (UCP), which can be used to treat terrible
      triad injuries. The present study anatomically examined the extensile EDC
      splitting approach for exposing the UCP. METHODS: Twenty fresh frozen cadaveric
      upper limbs were dissected. The splitting length of the EDC and detachment length
      of the extensor carpi radialis brevis (ECRB)-extensor carpi radialis longus
      (ECRL)-brachioradialis (BR) origin were measured to expose the UCP. The distance
      between the most distal site of the EDC splitting and the point at which the
      posterior interosseous nerve (PIN) crosses the anterior aspect of the radial
      shaft, and the distance between the most proximal site of the ECRB-ECRL-BR origin
      detachment and the point at which the radial nerve crosses the anterior aspect of
      the humeral shaft were measured. RESULTS: The splitting length of the EDC was
      45.4 +/- 4.8 mm, the detachment length of the ECRB-ECRL-BR origin was 30.2 +/-
      4.7 mm, the distance between the distal site of the EDC splitting and PIN was
      10.6 +/- 6.1 mm (minimum distance, 1.1 mm), and the distance between the proximal
      site of the ECRB-ECRL-BR origin detachment and the radial nerve was 49.5 +/- 9.7
      mm (minimum distance, 31.7 mm). CONCLUSIONS: The extensile EDC splitting approach
      can sufficiently expose the UCP. However, splitting must be performed carefully
      because the most distal site of the EDC splitting is close to the point at which
      the PIN crosses the anterior aspect of the radial shaft (average distance, 10 mm;
      minimum distance, 1 mm).

PMID- 27032619
TI  - [Biomarkers of severe bacterial infection: Do they help in clinical practice?].

PMID- 27032620
TI  - A national study of kidney graft tumor treatments: Toward ablative therapy.
AB  - BACKGROUND: Results of the conservative treatment of renal cell carcinomas
      arising in functional renal transplants are unknown compared to transplant
      nephrectomy. Only small series or case reports have been reported. METHODS: Data
      were collected from 32 transplantation centers nationwide on cases of de novo
      tumors in functional renal transplants presumed to be malignant between January
      1988 and December 2013. RESULTS: Among 116 de novo transplant tumors, 62 were
      treated conservatively including: 48 by partial nephrectomy (PN) and 14 by
      thermal ablation (TA). These patients were compared to 30 other patients who were
      treated by transplant nephrectomy. The median age of the transplanted kidneys at
      the time of diagnosis was 43.5 years old as calculated from the donor's age.
      Tumors treated by transplant nephrectomy presented more often with symptoms
      (pain, fever, impaired condition, hematuria) than tumors treated conservatively
      (P = .019). After PN, final histology showed 27 (47.5%) papillary carcinomas, 19
      (32.2%) clear cell carcinomas, 1 mixed carcinoma, and 2 oncocytomas. The median
      tumor size treated by PN was 24 mm with no difference in comparison to the TA
      group. Nine patients treated by PN had postoperative complications (21%),
      including 4 requiring operative intervention (Clavien IIIb). None of the patients
      treated by TA had complications. Specific survival was 100% at the time of last
      follow-up (median time after treatment 37 months) for patients treated by PN or
      TA. CONCLUSION: PN proved to be efficient in the treatment of small tumors of
      transplanted kidneys with good long-term functional and oncologic outcomes,
      including avoiding return to dialysis. TA seems to be an alternative therapy with
      good results in selected patients.

PMID- 27032621
TI  - Modified associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) procedure with right anterior liver sector congestion: Friend
      or foe?

PMID- 27032622
TI  - Precision medical communication to optimize stakeholder information exchange: a
      '4M-Quadrant' approach.
AB  - Personalized and precision medicine concepts have transformed the healthcare
      delivery environment from research and development to commercialization.
      Precision medical communication (PMC) represents a strategy to maximize
      personalized healthcare elements in medical-related exchanges to optimize value
      from the activity for the associated stakeholders. It is a discipline of
      developing the right message through the right mechanism at the right moment to
      the right healthcare member. PMC enhances the value of information exchange among
      stakeholders because it integrates data, analytics, and environmental and medical
      insights to efficiently disseminate more precise content to specified audiences
      in a balanced and compliant manner.

PMID- 27032623
TI  - Distribution behaviour of acaricide cyflumetofen in tomato during home canning.
AB  - The distribution behaviour of cyflumetofen in tomatoes during home canning was
      studied. The targeted compound cyflumetofen was determined by ultra-performance
      liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) after
      each process step, which included washing, peeling, homogenisation, simmering and
      sterilisation. Results indicated that more cyflumetofen was removed by washing
      with detergent solution compared with tap water, 2% NaCl solution and 2% CH3COOH
      solution. Peeling resulted in 90.2% loss of cyflumetofen and was the most
      effective step at removing pesticide residues from tomatoes. The processing
      factors (PFs) of tomato samples after each step were generally less than 1; in
      particular, the PF of the peeling process for cyflumetofen was 0.28. 

PMID- 27032624
TI  - [Prevention and treatment of mucositis in children with oral cancers: Practical
      recommendations].
AB  - Oral mucositis is an inflammation of the mucosa of the oral cavity of various
      etiologies. This is a common and debilitating complication in children treated
      with chemoradiotherapy for cancer. Its management remains a major concern both
      for the doctor than the patient. It affects the quality of life of patients and
      families. It may initiate the functional and vital prognosis because of the
      judgment of cancer treatment. Several treatment options are available, but there
      is no clear consensus therapeutic especially for the pediatric population. We
      have identified, through a comprehensive literature search indexed publications
      on this subject in order to review the pharmacological and non-pharmacological
      approaches that have been used to prevent and treat oral mucositis. Thus, current
      recommendations for the management of oral mucositis are very limited, and
      therefore the standard of care for this complication was palliative. In recent
      years several studies have revealed that the use of low-energy laser was
      particularly interesting in the prevention and treatment of radiation-induced or
      chemically induced mucositis. It significantly reduces the pain, the severity and
      duration of the ulcer by promoting wound healing. Randomized controlled trials
      with a large number of patients are expected to establish preventive and
      therapeutic protocols. Treatment with low power laser, known devoid of side
      effects, is a very promising oncology care to support radio-induced mucositis and
      chemotherapy. 

PMID- 27032626
TI  - Spray-dried solid dispersions containing ferulic acid: comparative analysis of
      three carriers, in vitro dissolution, antioxidant potential and in vivo anti
      platelet effect.
AB  - This article aimed to improve the relative solubility and dissolution rate of
      ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to
      ensure its in vitro antioxidant potential and to enhance its in vivo anti
      platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug
      concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000
      (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures
      (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray
      dried SDs containing FA were successfully obtained. Relative solubility of FA was
      improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations
      showed suitable drug content values close to 100%, whereas PLX-188 presented mean
      values between 70 and 90%. Agglomerates were observed depending on the carrier
      used. XRPD patterns and thermograms indicated that spray-drying led to drug
      amorphization and provided appropriate thermal stability, respectively. FTIR
      spectra demonstrated no remarkable interaction between carrier and drug for PEG
      6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which
      denoted intermolecular O-H***O = C bonds. Spray-dried SDs played an important
      role in enhancing dissolution rate of FA when compared to pure drug. The free
      radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10%
      SDs was kept. This formulation also provided a statistically increased in vivo
      anti-platelet effect compared to pure drug. In summary, these formulations
      enhanced relative solubility and dissolution rate of FA and chosen formulation
      demonstrated suitable in vitro antioxidant activity and improved in vivo anti
      platelet effect. 

PMID- 27032627
TI  - Interpersonal Psychotherapy for Mental Health Problems: A Comprehensive Meta
      Analysis.
AB  - OBJECTIVE: Interpersonal psychotherapy (IPT) has been developed for the treatment
      of depression but has been examined for several other mental disorders. A
      comprehensive meta-analysis of all randomized trials examining the effects of IPT
      for all mental health problems was conducted. METHOD: Searches in PubMed,
      PsycInfo, Embase, and Cochrane were conducted to identify all trials examining
      IPT for any mental health problem. RESULTS: Ninety studies with 11,434
      participants were included. IPT for acute-phase depression had moderate-to-large
      effects compared with control groups (g=0.60; 95% CI=0.45-0.75). No significant
      difference was found with other therapies (differential g=0.06) and
      pharmacotherapy (g=-0.13). Combined treatment was more effective than IPT alone
      (g=0.24). IPT in subthreshold depression significantly prevented the onset of
      major depression, and maintenance IPT significantly reduced relapse. IPT had
      significant effects on eating disorders, but the effects are probably slightly
      smaller than those of cognitive-behavioral therapy (CBT) in the acute phase of
      treatment. In anxiety disorders, IPT had large effects compared with control
      groups, and there is no evidence that IPT was less effective than CBT. There was
      risk of bias as defined by the Cochrane Collaboration in the majority of studies.
      There was little indication that the presence of bias influenced outcome.
      CONCLUSIONS: IPT is effective in the acute treatment of depression and may be
      effective in the prevention of new depressive disorders and in preventing
      relapse. IPT may also be effective in the treatment of eating disorders and
      anxiety disorders and has shown promising effects in some other mental health
      disorders.

PMID- 27032628
TI  - Effects of Citalopram on Neuropsychiatric Symptoms in Alzheimer's Dementia:
      Evidence From the CitAD Study.
AB  - OBJECTIVE: Citalopram has been shown to improve agitation in patients with
      Alzheimer's disease. The authors evaluated whether other neuropsychiatric
      symptoms improve with citalopram treatment compared with placebo. METHOD: In this
      planned secondary analysis of the Citalopram for Agitation in Alzheimer's Disease
      study, the authors evaluated the effect of citalopram on the 12 neuropsychiatric
      symptom domains assessed by the Neuropsychiatric Inventory (NPI). They compared
      caregiver-reported NPI scores at week 9 in patients receiving citalopram (30
      mg/day) or placebo with regard to both the presence or absence of individual
      neuropsychiatric symptoms and individual domain scores (reflecting severity) in
      participants who had symptoms at week 9. RESULTS: At week 9, participants treated
      with citalopram were significantly less likely to be reported as showing
      delusions (odds ratio=0.40), anxiety (odds ratio=0.43), and irritability/lability
      (odds ratio=0.38). A comparison of median scores of participants with symptoms
      present at week 9 showed significant differences favoring citalopram for
      hallucinations and favoring placebo for sleep/nighttime behavior disorders.
      CONCLUSIONS: While dosage constraints must be considered because of citalopram's
      adverse effect profile, this agent's overall therapeutic effects in patients with
      Alzheimer's disease and agitation, in addition to efficacy for
      agitation/aggression, included reductions in the frequency of irritability,
      anxiety, and delusions; among patients who had these symptoms at week 9, they
      included a reduction in the severity of hallucinations but an increase in the
      severity of sleep/nighttime behavior disorders.

PMID- 27032629
TI  - Fatigue in the first year after traumatic brain injury: course, relationship with
      injury severity, and correlates.
AB  - The objectives of this study were to document the evolution of fatigue in the
      first year after traumatic brain injury (TBI), and to explore correlates of
      fatigue. Participants were 210 adults who were hospitalised following a TBI. They
      completed questionnaires 4, 8, and 12 months post-injury, including the
      Multidimensional Fatigue Inventory (MFI). Participants with severe TBI presented
      greater mental and physical fatigue, and reduced activity compared to
      participants with moderate TBI. For all MFI subscales except reduced motivation,
      the general pattern was a reduction of fatigue levels over time after mild TBI,
      an increase of fatigue after severe TBI, and stable fatigue after moderate TBI.
      Fatigue was significantly associated with depression, insomnia, cognitive
      difficulties, and pain at 4 months; the same variables and work status at 8
      months; and depression, insomnia, cognitive difficulties, and work status at 12
      months. These findings suggest that injury severity could have an impact on the
      course of fatigue in the first year post-TBI. Depression, insomnia, and cognitive
      difficulties remain strong correlates of fatigue, while for pain and work status
      the association with fatigue evolves over time. This could influence the
      development of intervention strategies for fatigue, implemented at specific times
      for each severity subgroup.

PMID- 27032630
TI  - Constructing "Packages" of Evidence-Based Programs to Prevent Youth Violence:
      Processes and Illustrative Examples From the CDC's Youth Violence Prevention
      Centers.
AB  - This paper describes the strategic efforts of six National Centers of Excellence
      in Youth Violence Prevention (YVPC), funded by the U.S. Centers for Disease
      Control and Prevention, to work in partnership with local communities to create
      comprehensive evidence-based program packages to prevent youth violence. Key
      components of a comprehensive evidence-based approach are defined and examples
      are provided from a variety of community settings (rural and urban) across the
      nation that illustrate attempts to respond to the unique needs of the communities
      while maintaining a focus on evidence-based programming and practices. At each
      YVPC site, the process of selecting prevention and intervention programs
      addressed the following factors: (1) community capacity, (2) researcher and
      community roles in selecting programs, (3) use of data in decision-making related
      to program selection, and (4) reach, resources, and dosage. We describe systemic
      barriers to these efforts, lessons learned, and opportunities for policy and
      practice. Although adopting an evidence-based comprehensive approach requires
      significant upfront resources and investment, it offers great potential for
      preventing youth violence and promoting the successful development of children,
      families and communities. 

PMID- 27032631
TI  - Pilot project at Hazira, India, for capture of carbon dioxide and its biofixation
      using microalgae.
AB  - The objective of the present study was to set up a small-scale pilot reactor at
      ONGC Hazira, Surat, for capturing CO2 from vent gas. The studies were carried out
      for CO2 capture by either using microalgae Chlorella sp. or a consortium of
      microalgae (Scenedesmus quadricauda, Chlorella vulgaris and Chlorococcum
      humicola). The biomass harvested was used for anaerobic digestion to produce
      biogas. The carbonation column was able to decrease the average 34 vol.% of CO2
      in vent gas to 15 vol.% of CO2 in the outlet gas of the carbonation column. The
      yield of Chlorella sp. was found to be 18 g/m2/day. The methane yield was 386 l
      CH4/kg VSfed of Chlorella sp. whereas 228 l CH4/kg VSfed of the consortium of
      algae.

PMID- 27032632
TI  - Evaluation of the treatment of reverse osmosis concentrates from municipal
      wastewater reclamation by coagulation and granular activated carbon adsorption.
AB  - Reverse osmosis concentrate (ROC) from municipal wastewater reclamation reverse
      osmosis (mWRRO) contains elevated concentrations of contaminants which pose
      potential risks to aquatic environment. The treatment of ROC from an mWRRO using
      granular activated carbon (GAC) combined pretreatment of coagulation was
      optimized and evaluated. Among the three coagulants tested, ferric chloride
      (FeCl3) presented relatively higher DOC removal efficiency than polyaluminium
      chloride and lime at the same dosage and coagulation conditions. The removal
      efficiency of DOC, genotoxicity, and antiestrogenic activity concentration of the
      ROC could achieve 16.9, 18.9, and 39.7 %, respectively, by FeCl3 coagulation
      (with FeCl3 dosage of 180.22 mg/L), which can hardly reduce UV254 and
      genotoxicity normalized by DOC of the DOM with MW <5 kDa. However, the post-GAC
      adsorption column (with filtration velocity of 5.7 m/h, breakthrough point
      adsorption capacity of 0.22 mg DOC/g GAC) exhibited excellent removal efficiency
      on the dominant DOM fraction of MW <5 kDa in the ROC. The removal efficiency of
      DOC, UV254, and TDS in the ROC was up to 91.8, 96, and 76.5 %, respectively, by
      the FeCl3 coagulation and post-GAC adsorption. Also, the DOM with both
      genotoxicity and antiestrogenic activity were completely eliminated by the GAC
      adsorption. The results suggest that GAC adsorption combined pretreatment of
      FeCl3 coagulation as an efficient method to control organics, genotoxicity, and
      antiestrogenic activity in the ROC from mWRRO system. 

PMID- 27032634
TI  - Erratum to: Biodegradation of a commercial mixture of the herbicides atrazine and
      S-metolachlor in a multi-channel packed biofilm reactor.

PMID- 27032633
TI  - Antibiofouling potential of quercetin compound from marine-derived
      actinobacterium, Streptomyces fradiae PE7 and its characterization.
AB  - An attempt has been made to isolate, purify and characterize antifouling compound
      from Streptomyces fradiae PE7 isolated from Vellar estuarine sediment,
      Parangipettai, South India. The microbial identification was done at species
      level based on its phenotypic, cell wall and molecular characteristics. Strain
      PE7 produced high quantity of antifouling compounds in agar surface fermentation
      when compared to submerged fermentation. In fermentation optimization, wide range
      of sugars, amino acids, minerals, pH, temperature and NaCl concentration was
      found to influence the antifouling compound production from the strain PE7.
      Antifouling compound PE7-C was purified from the crude extract by preparative
      TLC, and its activity against biofouling bacteria was confirmed by bioautography.
      Based on the physico-chemical characteristics, the chemical structure of the
      antifouling compound PE7-C was identified as quercetin (C15H10O7), a flavonoid
      class of compound with the molecular weight 302.23 g/mol. The purified quercetin
      was active against 18 biofouling bacteria with MIC range between 1.6 and 25
      MUg/ml, algal spore germination and mollusc foot adherence found at 100 MUg/ml
      and 306 +/- 19.6 MUg ml(-1) respectively. The present study, for the first time,
      reported quercetin from marine-derived Streptomyces sp. PE7 with antifouling
      activity. This also leads to the repurposing of quercetin for the development of
      antifouling agent. 

PMID- 27032635
TI  - Influence of selected environmental factors on the abundance of aerobic
      anoxygenic phototrophs in peat-bog lakes.
AB  - Aerobic anoxygenic phototrophs (AAPs) are photoheterotrophic prokaryotes that are
      widespread in many limnic and marine environments. So far, little is known about
      their distribution in peat-bog lakes. Seventeen peat-bog lakes were sampled
      during three summer seasons 2009, 2011, and 2012, and the vertical distribution
      of AAPs was determined by infrared epifluorescence microscopy. The analysis
      demonstrated that in the surface layers of the studied lakes, AAP abundance
      ranged from 0.3 to 12.04 * 10(5) cells mL(-1), which represents <1 to 18.3 % of
      the total bacteria. The vertical distribution of AAPs confirmed their presence in
      the upper parts of the water column with minimum numbers in the anoxic bottom
      waters. We have shown that the AAP abundance was significantly positively
      correlated with the water pH, and the highest proportion of photoheterotrophs was
      found in peat-bog lakes with a pH between 6.7 and 7.6. Our results demonstrated
      an influence of water acidity on the abundance of AAPs, which may reflect a
      fundamental difference in the microbial composition between acidic and pH neutral
      peat-bog lakes. 

PMID- 27032636
TI  - Sources and environmental processes of polycyclic aromatic hydrocarbons and
      mercury along a southern slope of the Central Himalayas, Nepal.
AB  - Semi-volatile pollutants can undergo long-range atmospheric transport from low
      altitude source regions to high-altitude regions and then accumulate in surface
      matrices (soil and plants). The Himalayas is the highest mountain range
      worldwide, but there have been limited studies on the source, transport, and
      deposition of polycyclic aromatic hydrocarbons (PAHs) and mercury (Hg) in the
      region. In this study, atmospheric PAHs, and the PAHs and Hg in soil and foliage
      were determined along a transect on a southern slope of the Himalayas, Nepal. The
      study showed anthropogenic emissions of PAHs and Hg occurred in the lowland areas
      of Nepal, and upslope transport to the high-altitude regions happened for both
      pollutants. During the upslope transport, forest filter effect and snow
      scavenging may be the important factors that enhance the deposition of PAHs,
      contributing to the negative pattern between concentrations of PAHs and
      altitudes. On the contrary, more Hg accumulated in the high Himalayas, relating
      to the enhanced deposition in the high altitude caused by the higher input from
      upper atmosphere. Graphical abstract Distribution and environmental processes of
      PAHs and Hg along the southern slope of Himalayan mountain. 

PMID- 27032637
TI  - Endocrine disruptors in blue mussels and sediments from the Gulf of Gdansk
      (Southern Baltic).
AB  - Samples of blue mussel (Mytilus trossulus) and sediment were collected in the
      Gulf of Gdansk (Southern Baltic Sea) to assess the extent of their contamination
      with two groups of endocrine disruptors: 4-nonylphenols and organotins (butyl-
      and phenyltins). Five sampling stations were chosen along the coastline of the
      Tricity Agglomeration (Gdansk, Sopot, Gdynia) in 2008, 2012, and 2013. No evident
      differences between the three campaigns were found in either the mussel or the
      sediment samples. The mussels were moderately contaminated with 4-nonylphenols
      (30-111 ng g(-1) d.w.), whereas the levels of these compounds in the sediment
      samples were very low (0.8-2.7 ng g(-1) d.w.). Total concentrations of butyltin
      compounds in the mussels and sediments ranged between 41 and 164 ng Sn g(-1)
      d.w., and from below the limit of detection to 22 ng Sn g(-1) d.w., respectively,
      whereas phenyltins were not detected in any of the samples. Butyltin degradation
      indices indicate an old tributyltin input into the coastal environment, which is
      characterized by intense maritime activity. The results obtained from this work
      demonstrate that 5 years after the total ban on using organotin-based antifouling
      paints was imposed, butyltins are still present in mussels and sediments of the
      Gulf of Gdansk. 

PMID- 27032638
TI  - Clinical Profile of Atypical Manifestations of Dengue Fever: Correspondence.

PMID- 27032639
TI  - Montelukast as an add-on treatment in steroid dependant nephrotic syndrome,
      randomised-controlled trial.
AB  - BACKGROUND: The underlying mechanisms of nephrotic syndrome (NS) are still under
      debate and the need for more effective and less toxic treatment is challenging.
      We aimed to evaluate the efficacy of montelukast, a leukotriene receptor
      antagonist as an add-on therapy, and to explore the leukotriene (LT) biology in
      steroid-dependent nephrotic syndrome (SDNS). METHODS: A randomized controlled
      trial was conducted including 32 patients with SDNS who were randomly assigned to
      receive standard steroid treatment only [low-dose steroid (LDS) group] or
      standard steroid therapy plus montelukast (Montelukast group). Urine
      protein/creatinine ratio, serum albumin, creatinine, cholesterol, and plasma LTs
      (LTB4/C4/D4/E4) were evaluated in all patients before and after treatment.
      RESULTS: After treatment, both groups showed a significant decrease of LTB4 and
      LTC4/D4/E4. Further, the Montelukast group showed a significant decrease in serum
      creatinine and a significant increase in diastolic blood pressure and
      protein/creatinine ratio. It also showed a marked decrease in plasma LTC4/D4/E4
      compared to the LDS group, although not statistically significant. CONCLUSIONS:
      Our findings highlight the effect of montelukast on renal function, but suggest
      that the clinical and laboratory efficacy of the addition of montelukast to
      steroids in maintenance treatment of SDNS is debatable.

PMID- 27032640
TI  - The ability of external immobilizers to restrict movement of the cervical spine:
      a systematic review.
AB  - PURPOSE: To review the ability of various types of external immobilizers to
      restrict cervical spine movement. METHODS: With a systematical review of original
      scientific articles, data on range of motion, type of used external
      immobilization device and risk of bias were extracted. The described external
      immobilization devices were grouped and the mean restriction percentage and
      standard deviation were calculated. Finally, each device was classified based on
      its ability to restrict movement of the cervical spine, according to five levels
      of immobilization: poor (MIL <20 %), fair (MIL 20-40 %), moderate (MIL 40-60 %),
      substantial (MIL 60-80 %), and nearly complete (MIL >=80 %). RESULTS: The ability
      to reduce the range of motion by soft collars was poor in all directions. The
      ability of cervico-high thoracic devices was moderate for flexion/extension but
      poor for lateral bending and rotation. The ability of cervico-low thoracic
      devices to restrict flexion/extension and rotation was moderate, while their
      ability to restrict lateral bending was poor. All cranio-thoracic devices for non
      ambulatory patients restricted cervical spine movement substantial in all
      directions. The ability of vests with non-invasive skull fixation was substantial
      in all directions. No studies with healthy adults were identified with respect to
      cranial traction and halo vests with skull pins and their ability to restrict
      cervical movement. CONCLUSIONS: Soft collars have a poor ability to reduce
      mobility of the cervical spine. Cervico-high thoracic devices primarily reduce
      flexion and extension, but they reduce lateral bending and rotation to a lesser
      degree. Cervico-low thoracic devices restrict lateral bending to the same extent
      as cervico-high thoracic devices, but are considerably more effective at
      restricting flexion, extension, and rotation. Finally, cranio-thoracic devices
      nearly fully restrict movement of the cervical spine.

PMID- 27032641
TI  - Resistance to antibiotics: limit theorems for a stochastic SIS model structured
      by level of resistance.
AB  - The rise of bacterial resistance to antibiotics is a major Public Health concern.
      It is the result of two interacting processes: the selection of resistant
      bacterial strains under exposure to antibiotics and the dissemination of
      bacterial strains throughout the population by contact between colonized and
      uncolonized individuals. To investigate the resulting time evolution of bacterial
      resistance, Temime et al. (Emerg Infect Dis 9:411-417, 2003) developed a
      stochastic SIS model, which was structured by the level of resistance of
      bacterial strains. Here we study the asymptotic properties of this model when the
      population size is large. To this end, we cast the model within the framework of
      measure valued processes, using point measures to represent the pattern of
      bacterial resistance in the compartments of colonized individuals. We first show
      that the suitably normalized model tends in probability to the solution of a
      deterministic differential system. Then we prove that the process of fluctuations
      around this limit tends in law to a Gaussian process in a space of distributions.
      These results, which generalize those of Kurtz (CBMS-NSF regional conference
      series in applied mathematics, vol 36. Society for Industrial and Applied
      Mathematics (SIAM), Philadelphia, 1981, chap. 8) on SIR models, support the
      validity of the deterministic approximation and quantify the rate of convergence.

PMID- 27032642
TI  - Options in Prophylactic Surgery to Prevent Ovarian Cancer in High-Risk Women: How
      New Hypotheses of Fallopian Tube Origin Influence Recommendations.
AB  - OPINION STATEMENT: In women at increased risk of developing ovarian cancer, risk
      reducing salpingo-oophorectomy is the only intervention that has been shown to
      decrease mortality from ovarian cancer and is the standard of care for risk
      reduction. Prophylactic salpingectomy with delayed oophorectomy should be
      considered in high-risk premenopausal women in the setting of a clinical trial.

PMID- 27032643
TI  - Esophagogastric Adenocarcinoma: Is More Chemotherapy Better?
AB  - OPINION STATEMENT: Two cycles of neoadjuvant cisplatin and fluoropyrimidine (CF)
      and 6 cycles of perioperative CF with or without epirubicin are an evidence-based
      approach in operable esophageal and esophagogastric junctional adenocarcinomas.
      Three-drug regimens with anthracycline or taxane are associated with
      significantly higher tumor regression rates, with an expected increase in
      toxicity. In order to achieve an R0 resection and consequently a survival
      advantage, in selected patients having a risk of a threatened margin or
      incomplete resection, chemotherapy might be continued beyond 2 cycles if a
      response has been demonstrated. In metastatic setting, multidrug combination
      regimens have demonstrated a significant survival benefit when compared to single
      agent regimes. A three-drug regimen should be considered for fit patients and/or
      when a response is required for symptom control. The expected increase in
      toxicity needs to be carefully considered and discussed with patients. The choice
      to use a taxane in first-line setting may limit the options of second-line
      treatment to irinotecan-containing regimens and also precludes the use of
      anthracyclines in the first line. For this reason, we prefer to reserve taxane
      based therapy for the second-line setting.

PMID- 27032644
TI  - Watch and Wait: Is Surgery Always Necessary for Rectal Cancer?
AB  - OPINION STATEMENT: Despite decades of high-quality research, the treatment of
      rectal cancer remains a work in progress. The interplay between chemotherapy,
      radiotherapy, and surgery is under constant rearrangement and refinement. Through
      this all, the desire to preserve the anal sphincters and quality of life remains
      at the forefront. In the past decade, standard of care for stage II or III rectal
      cancers in the USA has been neoadjuvant chemoradiation therapy (CRT) followed by
      radical surgical resection of the rectum. While timing and sequence of the CRT
      continues to evolve, surgical resection has remained essential in treatment. This
      stands in contrast to anal cancer, where surgery is reserved purely for salvage.
      This article describes a treatment strategy that attempts to treat rectal
      adenocarcinoma with CRT alone, reserving surgery for failure or salvage. Of the
      studies performed to date, a number are methodologically sound and show promise.
      However, the body of evidence has yet to reach a size to sway practitioners from
      the established trinity of chemotherapy, radiotherapy, and surgery.
      Interestingly, few trials administer post treatment full-dose systemic
      chemotherapy, which is the standard of care in patients undergoing surgical
      resection. Better identification of patients that will have complete cure from
      this approach, combined with long-term outcome data on salvage patients, is
      necessary for this therapy to be universally embraced.

PMID- 27032645
TI  - Integrated Palliative Care and Oncologic Care in Non-Small-Cell Lung Cancer.
AB  - OPINION STATEMENT: Palliative care integrated into standard medical oncologic
      care will transform the way we approach and practice oncologic care. Integration
      of appropriate components of palliative care into oncologic treatment using a
      pathway-based approach will be described in this review. Care pathways build on
      disease status (early, locally advanced, advanced) as well as patient and family
      needs. This allows for an individualized approach to care and is the best means
      for proactive screening, assessment, and intervention, to ensure that all
      palliative care needs are met throughout the continuum of care. Components of
      palliative care that will be discussed include assessment of physical symptoms,
      psychosocial distress, and spiritual distress. Specific components of these
      should be integrated based on disease trajectory, as well as clinical assessment.
      Palliative care should also include family and caregiver education, training, and
      support, from diagnosis through survivorship and end of life. Effective
      integration of palliative care interventions have the potential to impact quality
      of life and longevity for patients, as well as improve caregiver outcomes.

PMID- 27032646
TI  - PET-CT in Staging, Response Evaluation, and Surveillance of Lymphoma.
AB  - OPINION STATEMENT: Lymphoma represents a broad spectrum of diseases with diverse
      biology, clinical behavior, and imaging features. Functional imaging with 18-F
      fluorodeoxyglucose (FDG)-positron emission tomography combined with computed
      tomography (PET-CT) is widely recognized as the most sensitive and specific
      imaging modality for patients with lymphoma and is used as part of staging,
      response evaluation, and surveillance in patients with Hodgkin (HL) and non
      Hodgkin lymphoma (NHL). Recent efforts at standardizing the conduct and consensus
      interpretation of PET-CT have facilitated its use in patients on clinical studies
      and beyond. The role of PET-CT has been affirmed in some clinical situations,
      such as staging and end-of-treatment evaluation in Hodgkin lymphoma and diffuse
      large B cell lymphoma (DLBCL), and in the evaluation of aggressive transformation
      of an indolent lymphoma. However, the role of functional imaging in other
      histologies and clinical settings is not as clear given the higher rate of false
      positive results and the costs inherent to PET-CT. There is little evidence to
      suggest its utility or impact on outcome in most indolent lymphomas, or in the
      setting of post-treatment surveillance. In addition, there remains controversy
      about the value of PET-CT in early response assessment during active therapy,
      particularly in DLBCL. This review will evaluate the evidence surrounding the
      role of PET-CT in staging, response evaluation and surveillance of Hodgkin and
      non-Hodgkin lymphoma.

PMID- 27032648
TI  - Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences:
      A Comparative Study of HIV-1 Nef Allelic Variants.
AB  - Hydrogen exchange mass spectrometry can be used to compare the conformation and
      dynamics of proteins that are similar in tertiary structure. If relative
      deuterium levels are measured, differences in sequence, deuterium forward- and
      back-exchange, peptide retention time, and protease digestion patterns all
      complicate the data analysis. We illustrate what can be learned from such data
      sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of
      the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain.
      Regions with similar sequence could be compared between variants. Although much
      of the hydrogen exchange features were preserved across the five proteins, the
      kinetics of Nef binding to Hck SH3 were not the same. These observations may be
      related to biological function, particularly for ELI Nef where we also observed
      an impaired ability to downregulate CD4 surface presentation. The data illustrate
      some of the caveats that must be considered for comparison experiments and
      provide a framework for investigations of other protein relatives, families, and
      superfamilies with HX MS. Graphical Abstract ?.

PMID- 27032649
TI  - Static, Mixed-Array Total Evaporation for Improved Quantitation of Plutonium
      Minor Isotopes in Small Samples.
AB  - Actinide isotope measurements are a critical signature capability in the modern
      nuclear forensics "toolbox", especially when interrogating anthropogenic
      constituents in real-world scenarios. Unfortunately, established methodologies,
      such as traditional total evaporation via thermal ionization mass spectrometry,
      struggle to confidently measure low abundance isotope ratios (<10(-6)) within
      already limited quantities of sample. Herein, we investigate the application of
      static, mixed array total evaporation techniques as a straightforward means of
      improving plutonium minor isotope measurements, which have been resistant to
      enhancement in recent years because of elevated radiologic concerns. Results are
      presented for small sample (~20 ng) applications involving a well-known plutonium
      isotope reference material, CRM-126a, and compared with traditional total
      evaporation methods. Graphical Abstract ?.

PMID- 27032650
TI  - Experimental Characterization of Secular Frequency Scanning in Ion Trap Mass
      Spectrometers.
AB  - Secular frequency scanning is implemented and characterized using both a benchtop
      linear ion trap and a miniature rectilinear ion trap mass spectrometer.
      Separation of tetraalkylammonium ions and those from a mass calibration mixture
      and from a pesticide mixture is demonstrated with peak widths approaching unit
      resolution for optimized conditions using the benchtop ion trap. The effects on
      the spectra of ion trap operating parameters, including waveform amplitude, scan
      direction, scan rate, and pressure are explored, and peaks at black holes
      corresponding to nonlinear (higher-order field) resonance points are
      investigated. Reverse frequency sweeps (increasing mass) on the Mini 12 are shown
      to result in significantly higher ion ejection efficiency and superior resolution
      than forward frequency sweeps that decrement mass. This result is accounted for
      by the asymmetry in ion energy absorption profiles as a function of AC frequency
      and the shift in ion secular frequency at higher amplitudes in the trap due to
      higher order fields. We also found that use of higher AC amplitudes in forward
      frequency sweeps biases ions toward ejection at points of higher order parametric
      resonance, despite using only dipolar excitation. Higher AC amplitudes also
      increase peak width and decrease sensitivity in both forward and reverse
      frequency sweeps. Higher sensitivity and resolution were obtained at higher trap
      pressures in the secular frequency scan, in contrast to conventional resonance
      ejection scans, which showed the opposite trend in resolution on the Mini 12.
      Mass range is shown to be naturally extended in secular frequency scanning when
      ejecting ions by sweeping the AC waveform through low frequencies, a method which
      is similar, but arguably superior, to the more usual method of mass range
      extension using low q resonance ejection. Graphical Abstract ?.

PMID- 27032651
TI  - MicroRNA-30 inhibits antiapoptotic factor Mcl-1 in mouse and human hematopoietic
      cells after radiation exposure.
AB  - We previously reported that microRNA-30 (miR-30) expression was initiated by
      radiation-induced proinflammatory factor IL-1beta and NFkB activation in mouse
      and human hematopoietic cells. However, the downstream effectors of miR-30 and
      its specific role in radiation-induced cell death are not well understood. In the
      present study, we evaluated effects of radiation on miR-30 expression and
      activation of intrinsic apoptotic pathway Bcl-2 family factors in in vivo mouse
      and in vitro human hematopoietic cells. CD2F1 mice and human CD34+ cells were
      exposed to different doses of gamma-radiation. In addition to survival studies,
      mouse blood, bone marrow (BM) and spleen cells and human CD34+ cells were
      collected at 4 h, and 1, 3 and 4 days after irradiation to determine apoptotic
      and stress response signals. Our results showed that mouse serum miR-30, DNA
      damage marker gamma-H2AX in BM, and Bim, Bax and Bak expression, cytochrome c
      release, and caspase-3 and -7 activation in BM and/or spleen cells were
      upregulated in a radiation dose-dependent manner. Antiapoptotic factor Mcl-1 was
      significantly downregulated, whereas Bcl-2 was less changed or unaltered in the
      irradiated mouse cells and human CD34+ cells. Furthermore, a putative miR-30
      binding site was found in the 3' UTR of Mcl-1 mRNA. miR-30 directly inhibits the
      expression of Mcl-1 through binding to its target sequence, which was
      demonstrated by a luciferase reporter assay, and the finding that Mcl-1 was
      uninhibited by irradiation in miR-30 knockdown CD34+ cells. Bcl-2 expression was
      not affected by miR-30. Our data suggest miR-30 plays a key role in radiation
      induced apoptosis through directly targeting Mcl-1in hematopoietic cells.

PMID- 27032652
TI  - Junior doctors' dispute: a pollster's view.

PMID- 27032654
TI  - Mental Health Service Use in Adolescence: Findings From the National Survey on
      Drug Use and Health.
AB  - OBJECTIVE: This study examined mental health service use, by service type, of
      adolescents ages 12-17. METHODS: Data were from approximately 113,000 adolescents
      who participated in the 2008-2012 National Survey on Drug Use and Health, an
      annual nationally representative survey of the civilian, noninstitutionalized
      U.S. POPULATION: Polynomial contrasts tested for linear and quadratic changes
      across age in the use of three types of past-year mental health services: school
      based services, outpatient therapist or clinic, and overnight hospital stay.
      RESULTS: Although mental health service use increased from age 12 to age 14
      across all service types, it decreased or stabilized from age 15 to 17. School
      based services were the most commonly used service and showed the steepest
      decline in use from age 12 to 17. CONCLUSIONS: Although adolescence can be marked
      by an increasing prevalence of mental disorders, mental health service use
      declined or leveled off for many service types by age 14 or 15.

PMID- 27032653
TI  - Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in
      Subjects with Environmental Asbestos Exposure.
AB  - INTRODUCTION: The purpose of this study was to investigate the potential value of
      certain biomarkers in predicting the presence of malignant pleural mesothelioma
      (MPM) in individuals environmentally exposed to asbestos. METHODS: This
      prospective study investigated three groups; a control group composed of 41
      healthy subjects, an asbestos exposure group consisting of 48 individuals, and a
      MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related
      peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR),
      fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined. RESULTS: Benign
      pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos
      exposure group. The asbestos exposure group had significantly higher mean TRX,
      SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011,
      and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM
      group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p =
      0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly
      lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX
      levels increased in a graded fashion among the control, asbestos exposure, and
      MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86
      and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI
      0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l
      (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2
      %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml
      (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The
      combination of the biomarkers reached a sensitivity of 100 %, but had lower
      specificity (as high as 27.7 %). CONCLUSIONS: Serum biomarkers may be helpful for
      early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a
      graded fashion from the controls to asbestos exposure and MPM groups. These two
      seem to be the most valuable biomarkers for the diagnosis of MPM, both
      individually and in combination.

PMID- 27032655
TI  - Incorporating Individualized Placement and Support Principles Into Vocational
      Rehabilitation for Formerly Incarcerated Veterans.
AB  - OBJECTIVE: This study evaluated the six-month outcomes of incorporating the
      principles of supported employment, specifically Individual Placement and Support
      (IPS), into the About Face program, an existing standardized group-based
      vocational program for previously incarcerated veterans. METHODS: Participants
      (N=84) with a history of at least one felony conviction and a substance use
      disorder (88%) or mental illness or combination (59%) were recruited from a large
      urban veterans hospital. Veterans were randomly assigned to either the About Face
      program (AF) or to that program plus a modification of IPS (AF+IPS). Veterans
      were followed for six months. Employment outcomes, including time to employment,
      hours worked, and income earned, were evaluated with survival analyses and
      nonparametric tests. RESULTS: Rates of employment over the follow-up period were
      significantly higher for those receiving AF+IPS, with 21 of 46 (46%) finding
      employment, compared with only eight of 38 (21%) who received AF alone. As a
      group, those receiving AF+IPS worked more hours and earned more wages than those
      receiving AF alone. CONCLUSIONS: Incorporating many of the principles and
      techniques of IPS into an existing vocational program was associated with
      improved employment outcomes over the six-month follow-up period and should be
      considered a viable rehabilitation option when working with this vulnerable
      population.

PMID- 27032656
TI  - Predictors of Antidepressant Nonadherence Among Older Veterans With Depression.
AB  - OBJECTIVE: Most depression among older adults is treated in primary care, and
      many patients do not adhere to medication treatment. The U.S. Department of
      Veterans Affairs (VA) has recently introduced initiatives to address such
      treatment gaps. This study examined patient-reported antidepressant nonadherence
      during the acute treatment period (first four months after a prescription) and
      identified predictors of nonadherence in a sample of older veterans. METHODS:
      This was a prospective, observational study of 311 participants ages 60 and older
      who received care at three VA medical centers and who had a diagnosis of
      clinically significant depression and were given a new outpatient antidepressant
      prescription. Participants completed an initial interview and a follow-up
      interview at four months after treatment recommendation. Antidepressant adherence
      was measured with a well-validated self-report measure. RESULTS: At four months,
      29% of participants reported nonadherence to their antidepressant medication. In
      unadjusted analyses, nonadherence was significantly associated with being African
      American, having no spouse or significant other, having greater general medical
      comorbidity, and receiving the prescription in a primary care setting (versus a
      specialty mental health setting). In logistic regression models controlling for
      several variables (demographic, illness, and functional status variables; type of
      antidepressant; contact with a therapist; medical setting; and site of
      recruitment), two predictors remained significantly associated with nonadherence:
      African-American race (odds ratio [OR]=4.23, p<.001) and general medical
      comorbidity (OR=1.33, p=.002). CONCLUSIONS: The two main predictors of
      nonadherence among older adults with depression were African-American race and
      general medical comorbidity. Results suggest that significant needs remain for
      important patient subgroups to improve antidepressant adherence.

PMID- 27032658
TI  - Associations Between Magnitude of Child Maltreatment and Medicaid Expenditures
      for Psychotropic Medications.
AB  - OBJECTIVE: This study examined relationships between various measures of the
      severity of child maltreatment and expenditures on psychotropic drugs among
      children in the welfare system. METHODS: Child participants (N=4,453) in the
      first National Survey of Child and Adolescent Well-Being (NSCAW) were linked to
      their Medicaid claims from 36 states. Three specifications for severity of
      maltreatment were developed. A two-part regression of logistic and generalized
      linear models of expenditures on psychotropic medications was estimated for each
      specification. RESULTS: Physically abused children had higher odds (odds ratio
      [OR]=1.34) and neglected children had lower odds (OR=.76) of incurring
      psychotropic drug expenditures. Children who experienced the most severe level of
      harm had higher odds (OR=1.33) of medication use, compared with children without
      appreciable harm. No maltreatment specifications were associated with increased
      expenditures on psychotropic drugs. CONCLUSIONS: The magnitude of maltreatment
      affected odds of use of psychotropic drugs but had no effect on Medicaid
      expenditures for these drugs.

PMID- 27032657
TI  - Glucose Testing for Adults Receiving Medicaid and Antipsychotics: A Population
      Based Prescriber Survey on Behaviors, Attitudes, and Barriers.
AB  - OBJECTIVE: This study aimed to assess provider attitudes about glucose testing
      for adults prescribed second-generation antipsychotic medication. METHODS:
      Missouri Medicaid prescribers of antipsychotics in 2011 were surveyed (N=924, 25%
      response rate). Pearson's chi square test was used to compare responses between
      prescriber specialty setting. Multivariable log-binomial regression evaluated the
      association of factors hypothesized as barriers to screening. RESULTS:
      Prescribers in community mental health centers were more likely than primary care
      providers to report that they would definitely order baseline testing (57% versus
      39%, p<.001) and were greater promoters of screening to colleagues (76% versus
      49%, p<.001). The strongest predictor of screening intent was disagreeing
      strongly that "metabolic screening is not a priority for me or my organization"
      (94% more likely to screen at drug initiation and 74% more likely at annual
      evaluation, both p<.001). CONCLUSIONS: Establishing organizational priority
      across all treatment settings is important for achieving population-based
      diabetes screening goals for all Medicaid patients receiving antipsychotics.

PMID- 27032659
TI  - Comparative Effectiveness of a Burnout Reduction Intervention for Behavioral
      Health Providers.
AB  - OBJECTIVES: Prior research found preliminary effectiveness for Burnout Reduction:
      Enhanced Awareness, Tools, Handouts, and Education (BREATHE), a daylong workshop
      for reducing burnout among behavioral health providers. Using a longer follow-up
      compared with prior research, this study compared the effectiveness of BREATHE
      and a control condition. METHODS: Behavioral health providers (N=145) from three
      U.S. Department of Veterans Affairs facilities and two social service agencies
      were randomly assigned to BREATHE or person-centered treatment planning. Burnout
      and other outcomes were compared across groups over time. RESULTS: Analyses
      yielded no significant differences between groups. However, BREATHE participants
      showed small but statistically significant improvements in cynicism (six weeks)
      and in emotional exhaustion and positive expectations for clients (six months).
      Participants in the control condition showed no significant changes over time.
      CONCLUSIONS: Although it did not demonstrate comparative effectiveness versus a
      control condition, BREATHE could be strengthened and targeted toward both
      distressed providers and their organizations.

PMID- 27032660
TI  - Factors Associated With Veterans' Access to Permanent Supportive Housing.
AB  - OBJECTIVE: The objective of this study was to identify individual- and program
      level characteristics associated with veterans' ability to move into permanent
      housing following receipt of a housing voucher and to identify factors associated
      with more rapid placement into housing. METHODS: This study used secondary
      quantitative and primary quantitative and qualitative data collected from
      veterans participating in the U.S. Department of Housing and Urban Development
      and U.S. Department of Veterans Affairs Supportive Housing program at four
      locations between 2008 and 2014 (N=9,967). Interviewers conducted in-person
      surveys with a subsample of the cohort (N=508). The study assessed two outcomes:
      whether a veteran accessed permanent supportive housing and the number of days
      required for veterans to move in. A logistic regression analysis identified
      predictors of becoming housed and a multiple regression model determined factors
      that influenced the time required for veterans to move into housing after
      admission to the program. RESULTS: Most (85%) veterans who received a permanent
      housing subsidy identified and moved into permanent housing. Receipt of
      outpatient behavioral health care in the 90 days before program admission and use
      of outpatient medical, behavioral health, or substance use care in the 90 days
      after increased the odds of becoming housed. CONCLUSIONS: Program-level policies
      may contribute to enhanced access to housing among veterans seeking permanent
      supportive housing, specifically a holistic approach to the frequent provision of
      supportive services-including both health care and case management-immediately
      after program admission.

PMID- 27032661
TI  - The IPS Learning Community: A Longitudinal Study of Sustainment, Quality, and
      Outcome.
AB  - OBJECTIVE: Implementations of evidence-based mental health practices often
      disappear quickly, and few studies have examined sustainment. Since 2001, the
      Individual Placement and Support (IPS) learning community has promoted
      dissemination, implementation, sustainment, and expansion of IPS by using
      multiple strategies: online training, in-person training and technical
      assistance, technical assistance teleconferences, annual meetings, stakeholder
      conference calls, fidelity assessments, and transparency of outcomes. This study
      examined sustainment of IPS over a two-year period among programs in the learning
      community in the United States. METHODS: The authors interviewed IPS team leaders
      in 129 programs actively participating in the learning community in 2012 and
      2014. The structured interview addressed questions about program status, funding,
      and quality improvement activities. Simultaneously, the learning community
      tracked program-level data on IPS fidelity and employment rates. The study
      examined two-year program sustainment and changes in employment rates, fidelity,
      funding, and quality improvement activities. RESULTS: In 2012, 129 participating
      sites had been active for an average of 4.5 years. At two-year follow-up, 124
      (96%) sites were sustained. The sustaining sites maintained quality improvement
      activities, expanded funding sources, and increased employment rates (41% to 43%;
      p=.04) and fidelity scores (103.8 to 108.4; p=.002). CONCLUSIONS: Nearly all
      programs participating in a learning community in 2012 continued to provide IPS
      services over the next two years, exceeding sustainment rates for evidence-based
      practices reported in the literature. Quality indicators also improved,
      suggesting that learning community activities fostered sustainment and quality.
      Controlled studies must compare specific learning community approaches with usual
      methods of sustainment.

PMID- 27032662
TI  - Factors Affecting Mental Health Service Utilization Among California Public
      College and University Students.
AB  - OBJECTIVE: Unmet need for mental health treatment among college students is a
      significant public health issue. Despite having access to campus mental health
      providers and insurance to cover services, many college students do not receive
      necessary services. This study examined factors influencing college students' use
      of mental health services. METHODS: Online survey data for 33,943 students and
      14,018 staff and faculty at 39 college campuses in California were analyzed by
      using logistic regressions examining the association between students' use of
      mental health services and student characteristics, campus environment, and the
      presence of a formal network of campus mental health clinics. RESULTS: Nineteen
      percent of students reported current serious psychological distress in the past
      30 days, and 11% reported significant mental health-related academic impairment
      in the past year. Twenty percent reported using mental health services while at
      their current college, 10% by using campus services and 10% off-campus services.
      Students on campuses with a formal network of mental health clinics were more
      likely than students at community colleges to receive mental health services
      (odds ratio [OR] range=1.68-1.69), particularly campus services (OR=3.47-5.72).
      Students on campuses that are supportive of mental health issues were more likely
      to receive mental health services (OR=1.22), particularly on campus (OR=1.65).
      Students with active (versus low) coping skills were consistently more likely to
      use mental health services. CONCLUSIONS: Establishing more campus mental health
      clinics, fostering supportive campus environments, and increasing students'
      coping skills may reduce unmet need for mental health services among college
      students.

PMID- 27032663
TI  - Exploring Personal Medicine as Part of Self-Directed Care: Expanding Perspectives
      on Medical Necessity.
AB  - OBJECTIVE: Self-directed care (SDC) offers flexibility in and control over mental
      health services. This study examined the types of goods and services that
      individuals with serious mental illness request in an SDC intervention. METHODS:
      Data were from a randomized controlled trial that enrolled adult participants
      receiving Medicaid-reimbursed services, with two years of expenditures at the 50%
      90% level of all Medicaid enrollees in the county and no hospitalizations within
      six months of the study. Data were analyzed for 60 participants randomly assigned
      to an SDC intervention, who were allowed to make requests for and purchase
      nontraditional goods and services through a noncapitated fund. Requests were
      coded by using the section on activities and participation of the World Health
      Organization's International Classification of Function, Disability, and Health
      (ICF) model. Descriptive statistics are presented for the categories of requests
      made by participants. RESULTS: The 60 participants made a total of 507 requests,
      representing 621 ICF codes. Requests ranged from 0 to 37 requests per person,
      with a mean of 8.45 requests. The average time to first request was 95.5 days.
      Most codes were in the area of self-care (19%) and general tasks and demands
      (19%). Among the 52 participants who made requests, the mean was 11.94 requests,
      which addressed an average of 5.60 unique needs. CONCLUSIONS: Individuals with
      serious mental illness identified personal-medicine strategies to address needs
      that are currently unmet by traditional mental health services. Self-directed
      care may be a service delivery option that allows consumers to access their own
      personal medicine and better address their needs.

PMID- 27032664
TI  - Prison and Community Populations at Ultra-High Risk of Psychosis: Differences and
      Challenges for Service Provision.
AB  - OBJECTIVE: The aim of the study was to explore the feasibility of expanding a
      community service for early detection of psychosis into a local London prison for
      men in the United Kingdom. METHODS: All new receptions to a local prison for men
      in South London were approached for routine screening. Those who met criteria for
      being at ultra-high-risk of psychosis were compared with a help-seeking sample
      from the community who met the same criteria. Clinical and sociodemographic
      characteristics were compared to determine whether the prison and community
      populations had similar profiles and mental health needs. RESULTS: Of 891
      prisoners screened, 44 (5%) met criteria for being at ultra-high risk of
      psychosis. The community sample consisted of 42 participants. Compared with the
      community group, prison participants had lower scores on almost all symptom
      measures, were less likely to have remained in school and completed exams, and
      were more likely to be in short-term accommodations and to be of black race
      ethnicity. Lifetime use of illicit drugs was similar between the groups, but
      recent use was much higher in the prison group. CONCLUSIONS: Expanding community
      services into custodial settings should take into account the different
      environment and needs of the prisoner population. Specifically, early detection
      and intervention services should target a broad range of mental health problems
      rather than psychosis alone.

PMID- 27032665
TI  - Development and Testing of the First-Episode Psychosis Services Fidelity Scale.
AB  - OBJECTIVE: The purpose of this study was to test the reliability and validity of
      the First-Episode Psychosis Services Fidelity Scale (FEPS-FS) and compare it with
      similar scales. METHODS: A fidelity scale was developed from previously
      identified essential components of first-episode psychosis services. The scale
      was tested in six programs in two countries and compared with three existing
      scales. RESULTS: Program data collection from multiple sources indicated the
      feasibility and reliability of the FEPS-FS (intraclass correlation coefficient
      for interrater reliability=.842; 95% confidence interval=.795-.882). Satisfactory
      programs scored an average of 86% of the maximum total score; the single
      unsatisfactory program scored 70%. Compared with the other scales, the FEPS-FS
      has fewer items, but it has the highest proportion of items common to all scales.
      CONCLUSIONS: The FEPS-FS is a feasible, compact, reliable, and valid measure of
      adherence to evidence-based practices for first-episode psychosis services that
      can be applied to any first-episode psychosis service.

PMID- 27032666
TI  - The Future of Psychiatric Collaboration in Federally Qualified Health Centers.
AB  - Federally qualified health centers (FQHCs) provide comprehensive care to
      underserved and disadvantaged populations. FQHCs now comprise the largest primary
      care network in the United States. Currently, many FQHCs provide limited access
      to psychiatric services; and when such services are available, most use
      traditional on-site psychiatric clinics. The author reviews the rationale for
      increasing access to behavioral health care in FQHCs by adopting collaborative
      models of care, describes challenges to adopting these models in FQHCs, and
      discusses ways to increase the primary care team's ability to support patient
      self-care and family functioning.

PMID- 27032668
TI  - Facial cutaneous squamous cell carcinoma.

PMID- 27032667
TI  - Facilitating Action for Suicide Prevention by Learning Health Care Systems.
AB  - The Mental Health Research Network (MHRN), funded by the National Institute of
      Mental Health to serve as a national laboratory to improve mental health care,
      includes researchers embedded in 13 health systems in 15 states. This column
      describes practice changes and effectiveness and exploratory research undertaken
      by MHRN partners when they found a sustained elevated risk of suicide attempts
      among patients who reported suicidal ideation on the nine-item Patient Health
      Questionnaire. Challenges described include finding common ground between what
      health care systems and funding agencies find compelling, choosing study designs
      that balance research and clinical tensions, and implementing studies in ways
      that minimize disruption to health systems. The authors conclude that the
      greatest benefit to working collaboratively with care system partners is the
      opportunity to improve care and to simultaneously measure the impact of change.

PMID- 27032669
TI  - Biological profiling of novel tricyclic inhibitors of bacterial DNA gyrase and
      topoisomerase IV.
AB  - OBJECTIVES: The objective of this study was to characterize the in vitro and in
      vivo biological properties of a novel series of small-molecule bacterial type IIA
      topoisomerase inhibitors. METHODS: Bacterial susceptibility testing was performed
      by broth microdilution. Resistance frequencies were determined by plating
      bacteria onto agar containing test compound and enumerating mutants. Bacteria
      were passaged using subinhibitory concentrations of antibacterials to generate
      resistance. Target enzyme inhibition was determined by exposure to antibacterials
      and DNA; topoisomers were visualized by gel electrophoresis. Oral and intravenous
      pharmacokinetic profiles were determined in mice. In vivo efficacy was determined
      using a mouse model of septicaemia and thigh infection with MSSA and MRSA,
      respectively. RESULTS: Representative compounds REDX04139, REDX05604 and
      REDX05931 demonstrated in vitro potency against a range of Gram-positive and
      fastidious Gram-negative pathogens. Clinical isolate testing revealed REDX04139
      and REDX05931 had MIC90 values of 0.25 and 0.5 mg/L, respectively, for MRSA and
      MIC90 values of 2 mg/L for streptococci. REDX04139 was bactericidal in vitro
      against Staphylococcus aureus at 8* MIC over 6 h. Pharmacokinetic profiling of
      REDX04139 and REDX05604 in mice revealed low clearance and excellent
      bioavailability (>=71%). REDX04139 provided 100% survival against S. aureus in a
      mouse septicaemia model, while REDX05604 reduced bacterial load by up to 3.7 log
      units in the MRSA mouse thigh infection model. CONCLUSIONS: Redx Pharma has
      discovered a novel series of topoisomerase inhibitors that are being further
      developed for drug-resistant bacteria.

PMID- 27032670
TI  - Enteral sesame oil therapeutically relieves disease severity in rat experimental
      osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common cause of joint pain, affecting
      approximately 15% of the population. Recent studies indicate that quadriceps
      muscle weakness is directly involved in the pathogenesis of OA-associated joint
      pain. Oxidative stress plays an important role in skeletal muscle dysfunction.
      Sesame oil is a natural product with excellent antioxidative property. However,
      whether sesame oil can decrease OA-induced joint pain has never been
      investigated. OBJECTIVE: The aim of the present study was to examine the effect
      of sesame oil on OA-induced joint pain in rats. DESIGN: OA-associated joint pain
      in rats was induced by medial meniscal transection in rats. Sesame oil (0, 1, 2,
      or 4 ml/kg/day, orally) was given to rats 7 days after OA induction, while the
      parameters were determined 7 days after sesame oil administration. RESULTS: Daily
      sesame oil treatment for 7 days significantly decreased OA-associated joint pain.
      Sesame oil decreased muscular interleukin-6 and increased citrate synthase
      activity and myosin heavy chain IIa mRNA expression. Furthermore, sesame oil
      decreased muscular lipid peroxidation, nuclear Nrf2 protein expression, and
      reactive oxygen species generations as well as increased glutathione production
      and glutathione peroxidase activity in OA rats. CONCLUSIONS: Sesame oil may
      relieve OA-associated joint pain by inhibiting quadriceps muscular oxidative
      stress, at least partially, in rats.

PMID- 27032671
TI  - Dietary supplementation of germinated pigmented rice (Oryza sativa L.) lowers
      dyslipidemia risk in ovariectomized Sprague-Dawley rats.
AB  - BACKGROUND: In the recent years, cases of elderly women suffering from metabolic
      diseases such as dyslipidemias brought about by hormonal imbalance after
      menopause are continuously increasing. In this regard, a continuous and
      escalating demand to develop a more functional and highly nutritional food
      product as an adjunct supplement that can help alleviate these diseases is still
      being sought. OBJECTIVE: This study investigated the effects of germinated
      blackish-purple rice cultivars Keunnunjami, Superjami, and reddish-brown cultivar
      Superhongmi in the lipid metabolism of ovariectomized Sprague-Dawley rats.
      METHOD: The animals were randomly divided into nine groups (n=5) and were
      supplemented with either non-germinated or germinated rice for 9 weeks. Then the
      plasma, liver, and fat samples were collected for the lipid metabolism effects
      analyses. RESULTS: Animals fed with germinated rice cultivars had improved lipid
      profile levels relative to the groups supplemented with non-germinated rice
      cultivars. The germinated rice groups, Keununjami and Superjami in particular,
      showed a low total cholesterol levels, high levels of high-density lipoproteins
      cholesterol, high fecal lipid output, low hepatic lipid values, and low hepatic
      adipocyte accumulation. There was also an increase in the rate of lipolysis and
      decrease in lipogenesis based on the lipid-regulating enzyme activity profiles
      obtained for the groups that fed on germinated rice. Also, results revealed that
      pigmented rice cultivars had superior effects in improving the lipid metabolism
      relative to the non-pigmented normal brown rice variety. CONCLUSION: Based on the
      results, this study suggests that germinated pigmented rice consumption can
      confer better lipid metabolism than ordinary white rice and constitutes as an
      effective functional food in alleviating the risk of having dyslipidemias like
      those suffering from menopausal co-morbidities.

PMID- 27032672
TI  - Granuphilin exclusively mediates functional granule docking to the plasma
      membrane.
AB  - In regulated exocytosis, it is generally assumed that vesicles must stably "dock"
      at the plasma membrane before they are primed to become fusion-competent.
      However, recent biophysical analyses in living cells that visualize fluorescent
      secretory granules have revealed that exocytic behaviors are not necessarily
      uniform: some granules beneath the plasma membrane are resistant to Ca(2+)
      triggered release, while others are accelerated to fuse without a pause for
      stable docking. These findings suggest that stable docking is unnecessary, and
      can even be inhibitory or nonfunctional, for fusion. Consistently, pancreatic
      beta cells deficient in the Rab27 effector, granuphilin, lack insulin granules
      directly attached to the plasma membrane in electron micrographs but nevertheless
      exhibit augmented exocytosis. Here we directly compare the exocytic behaviors
      between granuphilin-positive and -negative insulin granules. Although granuphilin
      makes granules immobile and fusion-reluctant beneath the plasma membrane, those
      granuphilin-positive, docked granules release a portion of granuphilin upon
      fusion, and fuse at a frequency and time course similar to those of granuphilin
      negative undocked granules. Furthermore, granuphilin forms a 180-nm cluster at
      the site of each docked granule, along with granuphilin-interacting Rab27a and
      Munc18-1 clusters. These findings indicate that granuphilin is an exclusive
      component of the functional and fusion-inhibitory docking machinery of secretory
      granules.

PMID- 27032673
TI  - Cathepsin A mediates susceptibility to atrial tachyarrhythmia and impairment of
      atrial emptying function in Zucker diabetic fatty rats.
AB  - AIMS: Type 2 diabetes (T2D) is an independent risk factor for atrial fibrillation
      (AF) and stroke. The serine protease cathepsin A (CatA) is up-regulated in
      diabetes and plays an important role in the degradation of extracellular
      peptides. This study sought to delineate the role of CatA for the development of
      atrial remodelling under diabetic conditions. METHODS AND RESULTS: Zucker
      Diabetic Fatty rats (ZDF) were treated with vehicle (n = 20) or CatA-inhibitor
      (SAR; 50 mg/kg; n = 20), and compared with age-matched non-diabetic littermates
      (Ctr, n = 20). Left-atrial (LA) emptying function [magnetic resonance imaging
      (MRI)] and atrial electrophysiological parameters were measured before sacrifice
      for histological and biochemical analysis. The impact of enhanced cardiac CatA
      expression on atrial remodelling was determined using CatA-transgenic mice. At
      the age of 9.5 months, atrial tissues of ZDF rats showed increased CatA gene
      expression and CatA-activity, along with increased AF-susceptibility and impaired
      LA-emptying function. CatA-inhibition reduced CatA-activity in ZDF comparable to
      Ctr values and decreased LA-fibrosis formation and connexin 43 lateralization.
      This was associated with shorter median duration of LA-tachyarrhythmia (12.0 +/-
      1.7 vs. 1.2 +/- 0.47 s, P < 0.01) induced by burst pacing and diminished regions
      of slow conduction. Cardiac MRI revealed better LA-emptying function parameters
      (active per cent emptying: 29 +/- 1 vs. 23 +/- 2%, P < 0.01) after CatA
      inhibition. CatA-inhibition reduced LA bradykinin-degrading activity in ZDF.
      Transgenic mice overexpressing CatA demonstrated enhanced atrial fibrosis
      formation and increased AF-susceptibility. CONCLUSION: T2D leads to
      arrhythmogenic atrial remodelling in ZDF rats. CatA-inhibition reduces LA
      bradykinin-degrading activity in ZDF and suppresses the development of atrial
      structural changes and AF-promotion, implicating CatA as an important mediator
      for AF-substrate in T2D.

PMID- 27032674
TI  - Preservation Macroscopic Entanglement of Optomechanical Systems in non-Markovian
      Environment.
AB  - We investigate dynamics of an optomechanical system under the non-Markovian
      environment. In the weak optomechanical single-photon coupling regime, we provide
      an analytical approach fully taking into account the non-Markovian memory
      effects. When the cavity-bath coupling strength crosses a certain threshold, an
      oscillating memory state for the classical cavity field is formed. Due to the
      existence of the non-decay optical bound state, a nonequilibrium optomechanical
      thermal entanglement is preserved even without external driving laser. Our
      results provide a potential usage to generate and protect entanglement via non
      Markovian environment. 

PMID- 27032675
TI  - Hb Belluno [beta111(G13)Val->Gly;beta133(H11)Val->Val (HBB: c.335T > G;402G >
      C)]: Incidental Detection of a New Clinically Silent beta Chain Variant During Hb
      A1c Determination by High Performance Liquid Chromatography.
AB  - A previously unreported beta chain variant, Hb Belluno [beta111(G13)Val
      >Gly;beta133(H11)Val->Val (HBB: c.335T > G;402G > C)], was incidentally
      discovered in a woman suffering from diabetes, during glycated hemoglobin (Hb
      A1c) assay. Its presence was suspected because of a small abnormal peak with a
      retention time just shorter than that of normal Hb A1c. Standard high performance
      liquid chromatography (HPLC), capillary zone electrophoresis (CZE) and agarose
      gel electrophoresis did not allow to separate the variant from Hb A. The reversed
      phase HPLC of globin chains showed the presence of a heterozygous beta-globin
      variant amounting to approximately 43.5% of the total beta chains. Later, this
      variant was found in five other members of the same family and DNA sequencing
      analysis confirmed a beta-globin gene mutation. The variant is clinically silent
      in all patients and showed a slight instability with both heat and isopropanol
      tests. The other three mutations at this locus also affect stability. Hemoglobin
      (Hb) variants may invalidate the results of Hb A1c analysis and could result in
      mismanagement of diabetes. A comment alerting the requesting clinician to the
      presence of the Hb variant must be appended to the Hb A1c result. Additionally,
      many Hb variants can be chromatographically and/or electrophoretically silent.
      Therefore, when the clinician suspects a variant Hb, it is not sufficient to get
      a negative response from an HPLC screening test to rule it out. A dialogue with
      the pathologist is essential, involving exchange of information and sharing a
      diagnostic work-up including surveys to assess Hb stability and oxygen affinity,
      as much as DNA sequencing. 

PMID- 27032676
TI  - Investigation of cone-beam CT image quality trade-off for image-guided radiation
      therapy.
AB  - It is well-known that projections acquired over an angular range slightly over
      180 degrees  (so-called short scan) are sufficient for fan-beam reconstruction.
      However, due to practical imaging conditions (projection data and reconstruction
      image discretization, physical factors, and data noise), the short-scan
      reconstructions may have different appearances and properties from the full-scan
      (scans over 360 degrees ) reconstructions. Nevertheless, short-scan
      configurations have been used in applications such as cone-beam CT (CBCT) for
      head-neck-cancer image-guided radiation therapy (IGRT) that only requires a small
      field of view due to the potential reduced imaging time and dose. In this work,
      we studied the image quality trade-off for full, short, and full/short scan
      configurations with both conventional filtered-backprojection (FBP)
      reconstruction and iterative reconstruction algorithms based on total-variation
      (TV) minimization for head-neck-cancer IGRT. Anthropomorphic and Catphan phantoms
      were scanned at different exposure levels with a clinical scanner used in IGRT.
      Both visualization- and numerical-metric-based evaluation studies were performed.
      The results indicate that the optimal exposure level and number of views are in
      the middle range for both FBP and TV-based iterative algorithms and the
      optimization is object-dependent and task-dependent. The optimal view numbers
      decrease with the total exposure levels for both FBP and TV-based algorithms. The
      results also indicate there are slight differences between FBP and TV-based
      iterative algorithms for the image quality trade-off: FBP seems to be more in
      favor of larger number of views while the TV-based algorithm is more robust to
      different data conditions (number of views and exposure levels) than the FBP
      algorithm. The studies can provide a general guideline for image-quality
      optimization for CBCT used in IGRT and other applications. 

PMID- 27032677
TI  - Origin of Boundary Populations in Medaka (Oryzias latipes Species Complex).
AB  - The Japanese wild population of the medaka fish (Oryzias latipes species complex)
      comprises two genetically distinct groups, the Northern and the Southern
      Populations, with boundary populations having a unique genotype. It is thought
      that the boundary populations have been formed through introgressive
      hybridization between the two groups, because they are fixed with the Northern
      alleles at two allozymic loci, with the Southern alleles at two other loci, and
      have a unique allele at one locus. In this study, we examined the genetic
      population structure of the boundary populations using genome-wide single
      nucleotide polymorphism (SNP) data. Most SNPs of the Toyooka population, a
      typical boundary population, were shared with the Northern Population, some were
      shared with the Southern Population, and the remaining SNPs were unique to this
      population, suggesting that the boundary populations originated and diverged from
      the Northern Population. Further analyses of different populations using SNPs at
      eight genomic loci indicated that the boundary populations at different locations
      share similar genomic constitutions, and can be genetically distinguished from
      typical Northern Populations by unique SNPs. In addition, the boundary
      populations in the Maruyama River Basin had Northern mitochondrial DNA (mtDNA),
      while others, from the Fukuda and Kishida River Basins and from the Kumihama Bay
      area, had Southern mtDNA. These findings suggested that the boundary populations
      originated from the Northern Population, and then their genomes diverged as a
      result of geographical isolation, followed by mtDNA introgression from the
      Southern Population that occurred independently in some populations. 

PMID- 27032678
TI  - Geographic Variation in Skull Morphology of the Large Japanese Field Mice,
      Apodemus speciosus (Rodentia: Muridae) Revealed by Geometric Morphometric
      Analysis.
AB  - We analyzed geographic variation in skull morphology of the large Japanese field
      mouse (Apodemus speciosus) and determined changes in skull morphology that
      occurred during the evolutionary history of A. speciosus in relation to the
      estimated distribution range in the last glacial maximum (LGM). We analyzed 1,416
      specimens from 78 localities using geometric morphometric techniques applied to
      the dorsal side of the cranium and mandible. While large variations within and
      among the populations in Honshu, Shikoku, and Kyushu were observed, geographic
      patterns were not observed. Hokkaido and peripheral island populations showed
      shared differentiation from the Honshu, Shikoku, and Kyushu populations with a
      larger skull and distinct mandible shape. In addition, these two groups also
      differed from each other in accumulated random shape variation. Common
      characteristics found in Hokkaido and peripheral island populations were
      considered to be the ancestral states, which were retained by geographic
      isolation from the main islands. Random variations in Hokkaido and the peripheral
      island populations were formed through stochastic processes in relation to their
      isolation. Characteristic morphologies widely found in the populations of Honshu,
      Shikoku, and Kyushu were considered to be derived states that expanded after
      separation from the peripheral islands. Complex geomorphology and a shift in
      distribution range related to climate change and altitudinal distribution are
      suggested to have formed the complex geographic variation in this species. 

PMID- 27032679
TI  - Origin of Japanese White-Eyes and Brown-Eared Bulbuls on the Volcano Islands.
AB  - The Ogasawara Archipelago comprises two groups of oceanic islands: the Bonin
      Islands, formed in the Paleogene, and the Volcano Islands, formed in the
      Quaternary. These groups are located within a moderate distance (ca. 160-270 km)
      of one another; thus, most land bird species are not distinguished as different
      subspecies. Two land birds, however, show unusual distribution. The Japanese
      white-eyes Zosterops japonicus originally inhabited only the Volcano Islands, but
      has been introduced to the Bonin Islands. The brown-eared bulbuls Hypsipetes
      amaurotis are distributed as a different subspecies. We investigated their
      genetic differences and divergences in the Ogasawara Archipelago using
      mitochondria DNA. The Volcano population of white-eyes had four endemic
      haplotypes that were divergent from one another, except for the Bonin population,
      which shared three haplotypes with the Volcano, Izu, and Ryukyu Islands and did
      not have any endemic haplotype. This is the first genetic suggestion that the
      Bonin population is a hybrid of introduced populations. With respect to bulbuls,
      the Volcano and Bonin Islands each had a single endemic haplotype. The Volcano
      haplotype is closest to a haplotype shared with Izu, the Japanese mainland, Daito
      and Ryukyu, whereas the Bonin haplotype is closest to one endemic to the south
      Ryukyu Islands. This indicates that the sources of the two bulbul populations can
      be geologically and temporally distinguished. The populations of the two species
      in the Ogasawara Archipelago are irreplaceable, owing to their genetic
      differences and should be regarded as evolutionarily significant units. In order
      to prevent introgression between the two populations, we must restrict
      interisland transfers. 

PMID- 27032680
TI  - Distribution of Holtodrilus truncatus, a Branchiobdellidan Ectosymbiotic on Atyid
      Shrimps in the Kii Peninsula, Western Japan, with Reference to Salinity Tolerance
      and Host Preference.
AB  - The distribution of the branchiobdellidan Holtodrilus truncatus (Liang, 1963),
      which is symbiotic on atyid shrimps, was surveyed in 26 river catchments,
      covering almost all of the Kii Peninsula, western Japan. Holtodrilus truncatus
      has been recorded in 10 rivers located from the southwest to northeast regions of
      the peninsula. Paratya compressa was the dominant host species in all rivers,
      with a lower prevalence on Caridina leucosticta, C. multidentata, C. typus, and
      Neocaridina denticulata. The longitudinal distribution of H. truncatus was
      limited to the middle and upper reaches, while its main host P. compressa
      occurred widely from the lower to the upper reaches. The numbers of H. truncatus
      and their cocoons per host increased in summer and decreased in winter, in
      accordance with the abundance of the host P. compressa. The body size of P.
      compressa was larger in individuals with H. truncatus than those without H.
      truncatus in some rivers, while in another river, sizes of the two groups were
      not different. A salinity tolerance experiment revealed that the threshold of
      salinity tolerance of H. truncatus occurred between 0-0.5%. A choice experiment
      between two host species showed that H. truncatus preferred C. leucosticta to C.
      multidentata, P. compressa to C. multidentata, and P. compressa to C.
      leucosticta. 

PMID- 27032681
TI  - Molecular Evidence for the Expansion of the Asian Cryptic Invader Hediste
      diadroma (Nereididae: Annelida) into the Northeast Pacific Habitats of the Native
      H. limnicola.
AB  - We used previously established molecular methods to determine how far the Asian
      invader nereidid worm Hediste diadroma has spread into northeast Pacific
      estuaries that are inhabited by the native congener H. limnicola. Further, we
      analyzed the mitochondrial DNA of 702 Hediste specimens collected from 27
      estuaries along 1,350 km of coastline in Washington, Oregon, and California, USA,
      to distinguish between the morphologically indistinguishable immature stages of
      these two species. In total, 377 specimens were identified as the invader H.
      diadroma and 325 were identified as the native H. limnicola. The invader H.
      diadroma was dominant at many sites in Puget Sound, Washington, and in the
      Columbia River estuary, Washington, and Oregon, suggesting that this species
      initially invaded estuaries in Washington or northern Oregon. In contrast, the
      native H. limnicola was dominant at intertidal sites in California and at
      subtidal sites in the Columbia River estuary. We also analyzed a partial
      nucleotide sequence from the mitochondrial cytochrome oxidase subunit I gene of
      H. diadroma in specimens collected from seven sites in the US and 11 sites in
      Japan, which showed no marked geographic differentiation between 18 US and 31
      Japanese haplotypes. This finding suggests that H. diadroma have been introduced
      repeatedly into US estuaries from many regions in Japan. 

PMID- 27032682
TI  - Diversity of Lipid Distribution in Fish Skeletal Muscle.
AB  - Adipose tissue is a lipid storage organ characterized by the pronounced
      accumulation of adipocytes. Although adipose tissues are found in various parts
      of the vertebrate body, it is unclear whether these tissues have a common
      ancestral origin or have evolved in several phylogenetic lineages by independent
      adipocyte accumulation events. To gain insight into the evolutionary history of
      vertebrate adipose tissues, we determined the distribution of adipocytes by oil
      red O staining in skeletal muscle of 10 teleost species spanning eight orders:
      Tetraodontiformes, Pleuronectiformes, Spariformes, Salmoniformes, Clupeiformes,
      Beloniformes, Osmeriformes, and Cypriniformes. Accumulation of adipocytes in the
      myoseptum was observed in many species, including red seabream, rainbow trout,
      Pacific herring, Pacific saury, zebrafish and giant danio. We also found some
      order-, species-, and swimming mode-specific distribution patterns of adipocytes:
      1) almost complete absence of intramuscular adipocytes in the order
      Tetraodontiformes (torafugu and spotted green pufferfish), 2) clear adipocyte
      accumulation in the inclinator muscles of fin in Japanese flounder, 3) a large
      intramuscular adipose tissue at the root of the dorsal fin in ayu, and 4) thick
      lipid layers consisting of subcutaneous adipose tissue and red muscle lipids in
      pelagic migratory fish (Pacific herring and Pacific saury). Of note, Pacific
      herring and Pacific saury are phylogenetically distinct species sharing a similar
      niche and swimming mode, suggesting that their analogous adipocyte/lipid
      distribution patterns are the consequence of convergent evolution. The
      potentially heterogeneous origin of adipose tissues has significant implications
      for the interpretation of their functional diversity. 

PMID- 27032683
TI  - Molecular Phylogeny of Cypridoid Freshwater Ostracods (Crustacea: Ostracoda),
      Inferred from 18S and 28S rDNA Sequences.
AB  - With the aim of exploring phylogenetic relationships within Cypridoidea, the most
      species-rich superfamily among the podocopidan ostracods, we sequenced nearly the
      entire 18S rRNA gene (18S) and part of the 28S rRNA gene (28S) for 22 species in
      the order Podocopida, with representatives from all the major cypridoid families.
      We conducted phylogenetic analyses using the methods of maximum likelihood,
      minimum evolution, and Bayesian analysis. Our analyses showed monophyly for
      Cyprididae, one of the four families currently recognized in Cypridoidea.
      Candonidae turned out to be paraphyletic, and included three clades corresponding
      to the subfamilies Candoninae, Paracypridinae, and Cyclocypridinae. We propose
      restricting the name Candonidae s. str. to comprise what is now Candoninae, and
      raising Paracypridinae and Cyclocyprininae to family rank within the superfamily
      Cypridoidea. 

PMID- 27032684
TI  - Antioxidant Defense System of Tadpoles (Eupemphix nattereri) Exposed to Changes
      in Temperature and pH.
AB  - Amphibians are highly susceptible to environmental changes, mainly at the larval
      stage during which they are restricted to small and ephemeral aquatic habitats,
      which are subject to large fluctuations of abiotic parameters, such as
      temperature and pH. Consequently, tadpoles experience changes in biochemical,
      physiological, and molecular processes related to the maintenance of homeostasis,
      which may lead them to an oxidative stress state. In the present study, we
      investigated the effects of stress caused by changes in temperature and pH on the
      antioxidant enzymes catalase (CAT), glucose-6-phosphate dehydrogenase (G6PDH),
      glutathione reductase (GR) and glutathione-S-transferase (GST) in tadpoles of
      Eupemphix nattereri. The results show that changes in temperature and pH
      conditions induce an antioxidant response in tadpoles. GST and GR showed
      temperature-dependent activities; GST activity was higher in tadpoles exposed to
      28 degrees C, whereas GR exhibited increased activity in response to 28 degrees C
      and 36 degrees C. At 32 degrees C, both GST and GR had the lowest activity. CAT
      was induced by treatments with acidic (pH 5.0) and alkaline (pH 8.5) pH. Tadpoles
      exposed to acidic pH also had increased GR activity. The G6PDH was not changed in
      either experiment. Our data demonstrate that E. nattereri possesses an efficient
      antioxidant defense system for coping with the damaging effects of heat and
      acidity/alkalinity conditions in water. The alterations in antioxidant enzymes
      are probably a result of immediate physiological adaptation of individuals in
      response to increased production of ROS under environmental stress conditions. 

PMID- 27032685
TI  - Molecular Cloning of Spergen-4, Encoding a Spermatogenic Cell-Specific Protein
      Associated with Sperm Flagella and the Acrosome Region in Rat Spermatozoa.
AB  - We used a differential display in combination with complementary DNA (cDNA)
      cloning approach to isolate a novel rat gene LOC690919 with an open reading frame
      of 1227-length nucleotides encoding a protein of 409 amino acids. This gene was
      designated as Spergen-4 (a spermatogenic cell-specific gene-4). Spergen-4 mRNA
      was highly expressed in testis, and its expression was detected in rat testis
      starting at three weeks of postnatal development and persisting up to adulthood.
      Mouse and human orthologs, which lack N-terminal 77 amino acid residues of rat
      Spegen-4, were found in the database. Immunofluorescence microscopy and
      immunoblot analysis demonstrated that Spergen-4 was not expressed in
      spermatogonia, spermatocytes, and round spermatids, but was restrictedly detected
      at sperm head, cytoplasm, and developing flagella of elongated spermatids in rat
      testis. In mature spermatozoa, Spergen-4 was detected at the acrosome region as
      well as the principal piece of flagella. Spergen-4 immunosignal disappeared from
      sperm heads on acrosome reaction induced by progesterone. These data suggest that
      Spergen-4 integrated into elongated spermatids during spermiogenesis serves as a
      constituent for acrosome region and flagella of rat spermatozoa. 

PMID- 27032686
TI  - On a New Species of Parasitic Barnacle (Crustacea: Rhizocephala), Sacculina
      shiinoi sp. nov., Parasitizing Japanese Mud Shrimps Upogebia spp. (Decapoda:
      Thalassinidea: Upogebiidae), Including a Description of a Novel Morphological
      Structure in the Rhizocephala.
AB  - The rhizocephalan Sacculina shiinoi sp. nov. parasitizes three species of
      Upogebia in Japan. It is described morphologically and compared with another
      Upogebia parasite, Sacculina upogebiae Shiino, 1943 from Japan and Korea. These
      two species are the only sacculinids that parasitize mud shrimps. DNA analyses
      clearly show the two species to be separate and not closely related. The cuticle
      differs in being provided with close-set, branched, and spiny excrescences in S.
      shiinoi, while it lacks excrescences, but forms small scales in S. upogebiae. In
      S. upogebiae, the bulbous sperm-producing part and the narrow receptacle duct are
      separated by a compartmentalized mid portion, which is missing in S. shiinoi. A
      ridge, having a thickened, fluffy cuticle with a U-shaped course, passes across
      the visceral mass between the two receptacle openings in S. shiinoi. Such a
      structure has never been described in other rhizocephalans, and its function is
      uncertain. 

PMID- 27032688
TI  - Energy correlations of photon pairs generated by a silicon microring resonator
      probed by Stimulated Four Wave Mixing.
AB  - Compact silicon integrated devices, such as micro-ring resonators, have recently
      been demonstrated as efficient sources of quantum correlated photon pairs. The
      mass production of integrated devices demands the implementation of fast and
      reliable techniques to monitor the device performances. In the case of time
      energy correlations, this is particularly challenging, as it requires high
      spectral resolution that is not currently achievable in coincidence measurements.
      Here we reconstruct the joint spectral density of photons pairs generated by
      spontaneous four-wave mixing in a silicon ring resonator by studying the
      corresponding stimulated process, namely stimulated four wave mixing. We show
      that this approach, featuring high spectral resolution and short measurement
      times, allows one to discriminate between nearly-uncorrelated and highly
      correlated photon pairs. 

PMID- 27032687
TI  - Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced
      glycation end-products in rhesus macaques with spontaneous hypertensive metabolic
      syndrome.
AB  - Hypertension is often associated with metabolic syndrome (MetS), and serves as a
      risk factor of MetS and its complications. Blood pressure circadian rhythm in
      hypertensive patients has been suggested to contribute to cardiovascular
      consequences and organ damage of hypertension. But circadian changes of BP and
      their response to drugs have not been clearly investigated in non-human primates
      (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive
      MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we
      investigate BP changes and its circadian rhythm, together with the effect of
      antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive
      monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We
      also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys.
      Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple
      beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP
      circadian rhythm restoration, and decreased plasma concentration of inflammation
      factors and advanced glycation end-products. In summary, we identified a
      naturally-developed hypertensive MetS NHP model, which is of great value in the
      studies on pathogenesis of MetS-associated hypertension and development of novel
      therapeutic strategies. We also provided multiple novel mechanistic insights of
      the beneficial effect of Eplerenone on MetS with hypertension. 

PMID- 27032689
TI  - A protein and mRNA expression-based classification of gastric cancer.
AB  - The overall survival of gastric carcinoma patients remains poor despite improved
      control over known risk factors and surveillance. This highlights the need for
      new classifications, driven towards identification of potential therapeutic
      targets. Using sophisticated molecular technologies and analysis, three groups
      recently provided genetic and epigenetic molecular classifications of gastric
      cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer
      Research Group). Suggested by these classifications, here, we examined the
      expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and
      performed unsupervised hierarchical clustering analysis using less expensive and
      widely available immunohistochemistry and in situ hybridization. Ultimately, we
      identified five groups of gastric cancers based on Epstein-Barr virus (EBV)
      positivity, microsatellite instability, aberrant E-cadherin, and p53 expression;
      the remaining cases constituted a group characterized by normal p53 expression.
      In addition, the five categories correspond to the reported molecular subgroups
      by virtue of clinicopathologic features. Furthermore, evaluation between these
      clusters and survival using the Cox proportional hazards model showed a trend for
      superior survival in the EBV and microsatellite-instable related adenocarcinomas.
      In conclusion, we offer as a proposal a simplified algorithm that is able to
      reproduce the recently proposed molecular subgroups of gastric adenocarcinoma,
      using immunohistochemical and in situ hybridization techniques.

PMID- 27032690
TI  - Striatal 5-HT6 Receptors Regulate Cocaine Reinforcement in a Pathway-Selective
      Manner.
AB  - The nucleus accumbens (NAc) in the ventral striatum integrates many neurochemical
      inputs including dopamine and serotonin projections from midbrain nuclei to
      modulate drug reward. Although D1 and D2 dopamine receptors are differentially
      expressed in the direct and indirect pathway medium spiny neurons (dMSNs and
      iMSNs, respectively), 5-HT6 receptors are expressed in both pathways, more
      strongly than anywhere else in the brain, and are an intriguing target for
      neuropsychiatric disorders. In the present study, we used viral vectors utilizing
      dynorphin or enkephalin promoters to drive expression of 5-HT6 receptors or green
      fluorescent protein (GFP) selectively in the dMSNs or iMSNs of the NAc shell.
      Rats were then trained to self-administer cocaine. Increased 5-HT6 receptor
      expression in dMSNs did not change any parameter of cocaine self-administration
      measured. However, increasing 5-HT6 receptors in iMSNs reduced the amount of
      cocaine self-administered under fixed-ratio schedules, especially at low doses,
      increased the time to the first response and the length of the inter-infusion
      interval, but did not alter motivation as measured by progressive ratio 'break
      point' analysis. Modeling of cocaine pharmacokinetics in NAc showed that
      increased 5-HT6 receptors in iMSNs reduced the rat's preferred tissue cocaine
      concentration at each dose. Finally, increased 5-HT6 receptors in iMSNs
      facilitated conditioned place preference for a low dose of cocaine. We conclude
      that 5-HT6 receptors in iMSNs of NAcSh increase the sensitivity to the
      reinforcing properties of cocaine, particularly at low doses, suggesting that
      these receptors may be a therapeutic target for the treatment of cocaine
      addiction.

PMID- 27032692
TI  - Shift work and 20-year incidence of acute myocardial infarction: results from the
      Kuopio Ischemic Heart Disease Risk Factor Study.
AB  - OBJECTIVES: It remains unclear whether different types of shift work impose
      similar risks for cardiovascular events in middle-aged workers, especially those
      with pre-existing ischaemic heart disease (IHD). This study investigated the
      relations between different shift types and incident acute myocardial infarction
      (AMI) among men with and without pre-existing IHD, respectively. METHODS: We
      analysed data on 1891 men, aged 42-60 years at baseline, in the prospective
      Kuopio Ischemic Heart Disease Risk Factor Study cohort, using Cox proportional
      hazard models with adjustment for demographic, biological, behavioural and
      psychosocial job factors. We evaluated the associations of baseline shift work
      with 20-year incidence of AMI, and their modification by pre-existing IHD, using
      both stratified analysis and models with product terms between shift work and
      IHD. RESULTS: Travelling work (at least 3 nights per week away from home) was
      strongly positively associated with AMI among men with IHD (HR=2.45, 95% CI 1. 08
      to 5.59) but not among men without (HR=0.93, 95% CI 0.43 to 2.00). No clear
      associations were found between other types of shift work and AMI for both men
      with and without IHD. On both additive and multiplicative scales, baseline IHD
      status positively modified the association of travelling work with AMI (relative
      excess risk for interaction=3.23, 95% CI -0.50 to 6.97, p for multiplicative
      interaction=0.044). CONCLUSIONS: We found mixed results for the associations
      between different types of shift work and AMI among those with and without pre
      existing IHD. Future research should investigate these associations and effect
      modification for a broad spectrum of work schedules.

PMID- 27032691
TI  - The first description of complete invertebrate arginine metabolism pathways
      implies dose-dependent pathogen regulation in Apostichopus japonicus.
AB  - In this study, three typical members representative of different arginine
      metabolic pathways were firstly identified from Apostichopus japonicus, including
      nitric oxide synthase (NOS), arginase, and agmatinase. Spatial expression
      analysis revealed that the AjNOS transcript presented negative expression
      patterns relative to those of Ajarginase or Ajagmatinase in most detected
      tissues. Furthermore, Vibrio splendidus-challenged coelomocytes and intestine,
      and LPS-exposed primary coelomocytes could significantly induce AjNOS expression,
      followed by obviously inhibited Arginase and AjAgmatinase transcripts at the most
      detected time points. Silencing the three members with two specific siRNAs in
      vivo and in vitro collectively indicated that AjNOS not only compete with
      Ajarginase but also with Ajagmatinase in arginine metabolism. Interestingly,
      Ajarginase and Ajagmatinase displayed cooperative expression profiles in arginine
      utilization. More importantly, live pathogens of V. splendidus and Vibrio
      parahaemolyticus co-incubated with primary cells also induced NO production and
      suppressed arginase activity in a time-dependent at an appropriate multiplicity
      of infection (MOI) of 10, without non-pathogen Escherichia coli. When increasing
      the pathogen dose (MOI = 100), arginase activity was significantly elevated, and
      NO production was depressed, with a larger magnitude in V. splendidus co
      incubation. The present study expands our understanding of the connection between
      arginine's metabolic and immune responses in non-model invertebrates. 

PMID- 27032693
TI  - THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves'
      orbitopathy.
AB  - Management of Graves' orbitopathy (GO) must be based on the correct assessment of
      activity and severity of the disease. Activity is usually assessed with the
      Clinical Activity Score, whereas severity is classified according to a European
      Group On Graves' Orbitopathy (EUGOGO) consensus statement as mild, moderate-to
      severe, and sight-threatening. Myopathic and chronic congestive forms are
      uncommon clinical presentations of GO. Restoration and maintenance of stable
      euthyroidism are recommended in the presence of GO.In moderate-to-severe disease,
      steroids have been widely employed and have shown to possess an anti-inflammatory
      activity, but about 20-30% of patients are not responsive and present recurrence.
      Some novel immunosuppressors have already been employed in clinical studies and
      have shown interesting results, although the lack of randomized and controlled
      trials suggests caution for their use in clinical practice. Potential targets for
      therapy in GO are the thyroid-stimulating hormone and the insulin-like growth
      factor 1 receptor on the fibroblasts, inflammatory cytokines, B and T cells, and
      the PIK3/mTORC1 signaling cascades for adipogenesis. A recent open study has
      shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent
      reports on the efficacy of rituximab have recently been challenged by randomized
      controlled trials.As the main goal of treatment is the well-being of the patient,
      the therapeutic strategy should be addressed to better suit the patient needs,
      more than improving one or more biological parameters. The increasing
      availability of new therapies will expand the therapeutic options for GO patients
      and allow the clinician to really personalize the treatment to better suit the
      patients' personal needs. 

PMID- 27032694
TI  - 'Incidental' and 'non-incidental' thyroid papillary microcarcinomas are two
      different entities.
AB  - OBJECTIVE: Papillary thyroid microcarcinomas (microPTC) may be 'incidental' (Inc
      microPTC), occasionally found at histology after surgery for benign disease or
      'non-incidental' (Non-Inc-microPTC), diagnosed on clinical grounds. It is unclear
      whether these different microPTC reflect the same disease. The aim of the study
      was to compare Inc-microPTC and Non-Inc-microPTC for clinical and histological
      features as well as for serum TSH, a known factor involved in PTC development.
      DESIGN: We evaluated histology and serum TSH levels of consecutive patients
      submitted to thyroidectomy for goiter with compressive symptoms or for
      cytological diagnosis suspicious/indicative of PTC. METHODS: In total, 665
      consecutive patients (259 with a single thyroid nodule, SN and 406 with a
      multinodular gland, MN) were included in the study. According to histology,
      patients were classified as: benign nodular goiter (Benign, n=291); Inc-microPTC
      (n=92); Non-Inc-microPTC (n=67) and PTC>=1cm (macroPTC, n=215). RESULTS: Inc
      microPTC were significantly more frequent in MN than in SN (66/406, 16.2% vs
      26/259, 10.0%, P=0.02). Patients with Inc-microPTC compared with Non-Inc-microPTC
      were older (mean age+/-s.d. 53.3+/-13.2 years vs 44.9+/-14.8 years, P=0.0002),
      had a smaller tumor size (median 4mm vs 9mm, P<0.0001), a higher frequency of
      multifocality (70/92, 76.1% vs 35/67, 52.2% P=0.001) and lower levels of TSH
      (median 0.6mIU/L, IR: 0.4-1.0mIU/L vs value 1. mIU/L, IR: 0.6-1.4mIU/L vs
      P=0.0001). CONCLUSION: Incidental and non-incidental papillary thyroid
      microcarcinomas appear to be two different entities.

PMID- 27032695
TI  - Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of
      Hsp90 by Designed Ligands.
AB  - Controlling biochemical pathways through chemically designed modulators may
      provide novel opportunities to develop therapeutic drugs and chemical tools. The
      underlying challenge is to design new molecular entities able to act as
      allosteric chemical switches that selectively turn on/off functions by modulating
      the conformational dynamics of their target protein. We examine the origins of
      the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90
      by allosteric modulators through atomistic molecular dynamics (MD) simulations
      and analysis of protein-ligand interactions. In particular, we focus on the cross
      talk between allosteric ligands and protein conformations and its effect on the
      dynamic properties of the chaperone's active state. We examine the impact of
      different allosteric modulators on the stability, structural and internal
      dynamics properties of Hsp90 closed state. A critical aspect of this study is the
      development of a quantitative model that correlates Hsp90 activation to the
      presence of a certain compound, making use of information on the dynamic
      adaptation of protein conformations to the presence of the ligand, which allows
      to capture conformational states relevant in the activation process. We discuss
      the implications of considering the conformational dialogue between allosteric
      ligands and protein conformations for the design of new functional modulators. 

PMID- 27032696
TI  - SERS as a tool for in vitro toxicology.
AB  - Measuring markers of stress such as pH and redox potential are important when
      studying toxicology in in vitro models because they are markers of oxidative
      stress, apoptosis and viability. While surface enhanced Raman spectroscopy is
      ideally suited to the measurement of redox potential and pH in live cells, the
      time-intensive nature and perceived difficulty in signal analysis and
      interpretation can be a barrier to its broad uptake by the biological community.
      In this paper we detail the development of signal processing and analysis
      algorithms that allow SERS spectra to be automatically processed so that the
      output of the processing is a pH or redox potential value. By automating signal
      processing we were able to carry out a comparative evaluation of the toxicology
      of silver and zinc oxide nanoparticles and correlate our findings with qPCR
      analysis. The combination of these two analytical techniques sheds light on the
      differences in toxicology between these two materials from the perspective of
      oxidative stress.

PMID- 27032697
TI  - Neighbourhood characteristics and the incidence of first-episode psychosis and
      duration of untreated psychosis.
AB  - BACKGROUND: The incidence of psychotic disorders varies between geographical
      areas and it has been hypothesized that neighbourhood-level factors may influence
      this variation. It is also plausible that the duration of untreated psychosis
      (DUP) is associated with neighbourhood characteristics. The aims of this study
      were to determine whether the incidence of first-episode psychosis (FEP) and the
      DUP are associated with the level of social deprivation, fragmentation, social
      capital and population density. METHOD: All individuals with a FEP from a
      geographical defined catchment area over a 5-year period were included. Age
      standardized incidence rates were calculated for each neighbourhood factor.
      RESULTS: A total of 292 cases of FEP were included in the study and 45% had a
      diagnosis of a schizophrenia-spectrum disorder. The age standardized incidence
      rate of FEP in the most deprived area was 72.4 [95% confidence interval (CI) 26.4
      162.7] per 100 000 person-years compared with 21.5 (95% CI 17.6-26.0) per 100 000
      person-years in the most affluent areas. This represents a 3.4-fold increase in
      FEP incidence in the most deprived areas. The incidence of FEP was also increased
      in neighbourhoods that were more socially fragmented [incidence rate ratio (IRR)
      = 2.40, 95% CI 1.05-5.51, p = 0.04] and there was a trend for the incidence to be
      increased in neighbourhoods with lower social capital (IRR = 1.43, 95% CI 0.99
      2.06, p = 0.05). The median DUP was 4 months and was higher in more socially
      fragmented neighbourhoods. CONCLUSIONS: The incidence of psychotic disorders is
      related to neighbourhood factors and it may be useful to consider neighbourhood
      factors when allocating resources for early intervention services.

PMID- 27032698
TI  - Trajectories of depressive symptoms after hip fracture.
AB  - BACKGROUND: Hip fracture is often complicated by depressive symptoms in older
      adults. We sought to characterize trajectories of depressive symptoms arising
      after hip fracture and examine their relationship with functional outcomes and
      walking ability. We also investigated clinical and psychosocial predictors of
      these trajectories. METHOD: We enrolled 482 inpatients, aged ?60 years, who were
      admitted for hip fracture repair at eight St Louis, MO area hospitals between
      2008 and 2012. Participants with current depression diagnosis and/or notable
      cognitive impairment were excluded. Depressive symptoms and functional recovery
      were assessed with the Montgomery-Asberg Depression Rating Scale and Functional
      Recovery Score, respectively, for 52 weeks after fracture. Health, cognitive, and
      psychosocial variables were gathered at baseline. We modeled depressive symptoms
      using group-based trajectory analysis and subsequently identified correlates of
      trajectory group membership. RESULTS: Three trajectories emerged according to the
      course of depressive symptoms, which we termed 'resilient', 'distressed', and
      'depressed'. The depressed trajectory (10% of participants) experienced a
      persistently high level of depressive symptoms and a slower time to recover
      mobility than the other trajectory groups. Stressful life events prior to the
      fracture, current smoking, higher anxiety, less social support, antidepressant
      use, past depression, and type of implant predicted membership of the depressed
      trajectory. CONCLUSIONS: Depressive symptoms arising after hip fracture are
      associated with poorer functional status. Clinical and psychosocial variables
      predicted membership of the depression trajectory. Early identification and
      intervention of patients in a depressive trajectory may improve functional
      outcomes after hip fracture.

PMID- 27032700
TI  - Impact on survival of timing and duration of adjuvant chemotherapy in radically
      resected gastric cancer.
AB  - PURPOSE: Adjuvant chemotherapy improves survival of patients with gastric cancer.
      Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA
      S) was a phase III study comparing sequential FOLFIRI followed by
      docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was
      not superior in terms of disease-free survival (DFS) and overall survival (OS).
      METHODS: The treatment was to be started within 8 weeks from surgery. This
      analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on
      outcomes. RESULTS: Out of 1,106 randomized, 1,072 patients without major
      violations of eligibility criteria and receiving at least one treatment cycle
      were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201
      (18.8%) cases, whereas it was completed without or with modifications in 277
      (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513
      progressions and 472 deaths occurred. A longer TSC was significantly associated
      with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00;
      p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for
      treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor
      stage. Better treatment compliance was associated with improved survival.
      CONCLUSIONS: Our findings suggest that longer TSC had at least no detrimental
      effect on DFS and OS, whereas treatment completion had a protective effect. Our
      findings need to be confirmed prospectively.

PMID- 27032701
TI  - "There's no reason why": a campaign to raise cancer awareness among adolescents.
AB  - INTRODUCTION: Adolescents with cancer often experience a longer diagnostic delay
      than children, mainly because they take longer to go to a doctor. The Italian
      Society for Adolescents with Oncohematological Diseases (SIAMO) has launched an
      information campaign focusing on raising adolescents' awareness of the importance
      of diagnosing cancer early. METHODS: The concepts of the campaign were developed
      by a scientific committee of clinicians, cancer patients and their parents, and
      marketing experts. The title of the campaign is "There's no reason why". A video
      has been launched on TV channels and the Internet, and the final frame refers
      viewers to the SIAMO website, which provides advice to help adolescents interpret
      any symptoms they experience. RESULTS: The video has had 12,181 views. In the 6
      months following the launch of the campaign, the SIAMO website page dedicated to
      the campaign was opened by 9,767 viewers for a total of 13,632 views.
      CONCLUSIONS: Though it remains very difficult to judge the efficacy of this
      initiative, the value of a campaign focusing on improving the adolescent
      population's cancer awareness is supported by the large number of studies
      published on the diagnostic delay in this age group. Our campaign goes to show
      the importance of ensuring cooperation between the different stakeholders
      involved in the global care of adolescents with cancer.

PMID- 27032702
TI  - To what extent is risk grouping method successful in deciding surgical staging in
      endometrial cancer?
AB  - PURPOSE: The aim of this investigation was to evaluate the success rate of risk
      grouping method for staging surgery by exploring the rate of lymph node
      metastasis (LNM) in patients with endometrial cancer (EC) according to low-risk
      (LR) and high-risk (HR) groups. METHODS: Patient files were reviewed
      retrospectively and the data of 268 patients were included in the study who
      underwent lymph node dissection (LND) for EC. Nodal status, histopathologic type,
      myometrial invasion (MI), tumor size (TS), and grade (G) were evaluated. In the
      LR group, all the criteria were required (G 1-2, <1/2 MI, type 1 histology, <2 cm
      TS), but in the HR group, one of them was enough (G 3 or >=1/2 MI or type 2
      histology or >=2 cm TS). RESULTS: A total of 84 (31.3%) and 184 (68.7%) patients
      were grouped LR and HR, respectively. In total, 23 patients had LNM (8.5%) out of
      268 surgically staged EC patients. Lymph node metastasis was significantly (p =
      0.001) more common in the HR group of patients (2.4%, 2/84 LR vs 11.4%, 21/184
      HR). Cancer-specific survival (CSS) rates in groups were 96.8% and 88.6%,
      respectively (p = 0.009). CONCLUSIONS: In patients with EC, there is a
      significant difference between LR and HR groups for LNM and CSS rates. But this
      method of stratification is not adequate to separate them for deciding whether
      surgical staging is mandatory. Moreover, even most of the HR patients (163/184,
      88.6%) are exposed to unnecessary LND. Perhaps they are not really HR and the HR
      definition needs to be revised.

PMID- 27032703
TI  - Cytotoxic extravasation: an issue disappearing or a problem without solution?
AB  - PURPOSE: The incidence and management of antitumoral compound extravasation that
      occurred in our medical day hospital unit were registered in a 10-year period.
      METHODS: A total of 114 episodes were consecutively recorded out of an estimated
      number of 211,948 administrations performed (0.05%). Type of compound,
      localization, timing, symptoms, treatment, resolution, or sequelae were
      documented. RESULTS: Extravasations after anthracyclines (17/114), platinum
      compounds (34/114), vinca alkaloids (7/114), and taxanes (34/114) were more
      frequently associated with edema and erythema +/- pain. Five cases of monoclonal
      antibodies extravasation were observed without sequelae. With the involvement of
      an interdisciplinary task force and the use of dedicated guidelines, conservative
      management was successful in all patients. In the great majority of cases,
      recovery was complete within 48 hours after antidote administration. The support
      of our pharmacy was crucial. Physiatric evaluation was considered in several
      cases. No patients required surgery. CONCLUSIONS: We confirm that the adopted
      standardized approach to this event resulted in a satisfactory outcome and could
      be suggested as appropriate for managing extravasation in a large clinical
      context.

PMID- 27032704
TI  - Chemically synthesized lithium peroxide composite cathodes for closed system Li
      O2 batteries.
AB  - A binder-free lithium peroxide-carbon nanofiber composite cathode was synthesized
      chemically to be used in a closed system lithium-oxygen battery without external
      supply of oxygen. This cathode enhances the closed system performance and
      exhibits good rechargeability with cyclability up to 50 cycles. This composite
      cathode provides scope for full cell development. 

PMID- 27032699
TI  - Immune responses against protozoan parasites: a focus on the emerging role of Nod
      like receptors.
AB  - Nod-like receptors (NLRs) have gained attention in recent years because of the
      ability of some family members to assemble into a multimeric protein complex
      known as the inflammasome. The role of NLRs and the inflammasome in regulating
      innate immunity against bacterial pathogens has been well studied. However,
      recent studies show that NLRs and inflammasomes also play a role during
      infections caused by protozoan parasites, which pose a significant global health
      burden. Herein, we review the diseases caused by the most common protozoan
      parasites in the world and discuss the roles of NLRs and inflammasomes in host
      immunity against these parasites.

PMID- 27032705
TI  - Effect of postpartum propylene glycol allocation to over-conditioned Holstein
      cows on concentrations of milk metabolites.
AB  - The objective of the study was to investigate the effect of propylene glycol (PG)
      allocation on concentrations of milk metabolites with potential use as indicators
      of glucogenic status in high yielding postpartum dairy cows. At time of calving,
      nine ruminally cannulated Holstein cows were randomly assigned to ruminal dosing
      of 500 g/d tap water (CON, n = 4) or 500 g/d PG (PPG, n = 5). The PG was given
      with the morning feeding week 1-4 postpartum (treatment period) and cows were
      further followed during week 5-8 postpartum (follow-up period). All cows were fed
      the same postpartum diet. Milk samples were obtained at each milking (3 times/d)
      in the treatment period, and at morning milking during the follow-up period.
      Weekly blood samples were obtained from -4 to +8 weeks relative to calving and
      daily blood samples from -7 until +7 d relative to calving. The main effect of PG
      allocation was an increased glucogenic status, e.g. visualised by a prompt marked
      increase in blood fructosamine. During the treatment period, milk concentration
      of free glucose tended to be greater, whereas milk concentrations of isocitrate
      and BHBA were lower for PPG compared with CON. It is proposed that the ratio
      between free glucose and isocitrate in milk may be a potential biomarker for
      glucogenic status in the vulnerable early postpartum period. We will pursue this
      issue in the future. 

PMID- 27032706
TI  - Application of Microwave-Induced Combustion and Isotope Dilution Strategies for
      Quantification of Sulfur in Coals via Sector-Field Inductively Coupled Plasma
      Mass Spectrometry.
AB  - In recent years, microwave-induced combustion (MIC) has proved to be a robust
      sample preparation technique for difficult-to-digest samples containing high
      carbon content, especially for determination of halogens and sulfur. National
      Institute of Standards and Technology (NIST) has applied the MIC methodology in
      combination with isotope dilution analysis for sulfur determinations,
      representing the first-reported combination of this robust sample preparation
      methodology and high-accuracy quantification approach. Medium-resolution mode
      sector-field inductively coupled plasma mass spectrometry was invoked to avoid
      spectral interferences on the sulfur isotopes. The sample preparation and
      instrumental analysis scheme was used for the value assignment of total sulfur in
      Standard Reference Material (SRM) 2682c Subbituminous Coal (nominal mass fraction
      0.5% sulfur). A description of the analytical procedures required is provided,
      along with metrological results, including an estimation of the overall method
      uncertainty (<1.5% relative expanded uncertainty) calculated using the IDMS
      measurement function and a Kragten spreadsheet approach.

PMID- 27032707
TI  - A Disease That Is Often Missed Without Gastrointestinal Symptoms.

PMID- 27032708
TI  - Massive Transfusion of 5 U Packed Redblood Cells, 3 U Fresh Frozen Plasma, and
      160 cc of Platelets in a 14-Month-Old Patient.
AB  - BACKGROUND: We present a case in which extremely rapid massive transfusion was
      successfully used to combat severe acute bleeding during a parietooccipital tumor
      resection in a 14-month-old patient. CASE REPORT: An 8-kg patient was found to
      have a 4 * 5 * 5-cm parietooccipital tumor on computed tomography scan, for which
      resection was urgently planned. Sudden acute bleeding was encountered, which was
      communicated to the anesthesia team. Transfusion was initiated and a total of 5
      units of packed red blood cells, 3 units of fresh frozen plasma, 160 ml of
      platelets, 200 ml of albumin, and 500 ml of 0.9% normal saline were transfused
      during a 4-h period. We administered 4 g of mannitol and 0.8 mg of furosemide to
      deal with anticipated fluid overload. The patient was sent to the intensive care
      unit and extubated the next day. No clinically significant hemostatic or fluid
      overload complications were noted after the treatment. CONCLUSIONS: Massive
      transfusion (MT) was found to be safe and effective in this case. Most of what we
      know about pediatric MT is an extrapolation of data from adult studies. Although
      practical, it might not be ideal due to the differences in the physiology and
      incomplete development of hemostatic mechanisms in children, especially those
      younger than 12 months. Studies evaluating the use of pediatric MT protocols have
      not shown a significant advantage over transfusion per clinician discretion.

PMID- 27032709
TI  - Muscle fiber type diversification during exercise and regeneration.
AB  - The plasticity of skeletal muscle can be traced down to extensive metabolic,
      structural and molecular remodeling at the single fiber level. Skeletal muscle is
      comprised of different fiber types that are the basis of muscle plasticity in
      response to various functional demands. Resistance and endurance exercises are
      two external stimuli that differ in their duration and intensity of contraction
      and elicit markedly different responses in muscles adaptation. Further, eccentric
      contractions that are associated with exercise-induced injuries, elicit varied
      muscle adaptation and regenerative responses. Most adaptive changes are fiber
      type-specific and are highly influenced by diverse structural, metabolic and
      functional characteristics of individual fiber types. Regulation of signaling
      pathways by reactive oxygen species (ROS) and oxidative stress also plays an
      important role in muscle fiber adaptation during exercise. This review focuses on
      cellular and molecular responses that regulate the adaptation of skeletal muscle
      to exercise and exercise-related injuries.

PMID- 27032710
TI  - Belamcanda chinensis (L.) DC-An ethnopharmacological, phytochemical and
      pharmacological review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Belamcanda chinensis (L.) DC is the sole species
      in the genus Belamcanda Adans. (Iridaceae), found mainly in Northeast Asia.
      Bombus chinensis has long been used in traditional Chinese medicine for its
      multiple therapeutic uses in the form of antipyretic agents, antidote,
      expectorant, antiphlogistic and analgesic. AIM OF THE REVIEW: This manuscript
      comprehensively summarizes the various studies published in recent years on the
      botany, ethnopharmacology, phytochemistry, biological activity and toxicology of
      B. chinensis. We hope to provide a foundation for future studies on the mechanism
      of action and development of better therapeutic agents based on B. chinensis.
      MATERIAL AND METHODS: All information available on B. chinensis was collected
      using electronic search engines, such as PubMed, SciFinder Scholar, CNKI, TPL
      (www.theplantlist.org), Google Scholar and Web of Science. RESULTS: The analysis
      shown that ethno-medical uses of B. chinensis have been recorded in China, Japan
      and Korea since a long time. Based on a phytochemical investigation, this plant
      contains flavonoids, terpenoids, quinones, phenolic compounds, ketones, organic
      acids, etc. Crude extracts and pure compounds isolated from B. chinensis
      exhibited various biological effects. CONCLUSIONS: In light of its long
      traditional use and the modern phytochemical and pharmacological studies
      summarized here, B. chinensis is known to be a promising medicinal plant with the
      isolated extracts and chemical components showing a wide range of biological
      activities. Thus, it is imperative that the necessary programs and value
      assessment of B. chinensis be established for further studies. It is also
      important that the synergistic or antagonistic effects of this traditional herbal
      medicine are investigated in depth to identify more bioactive components by
      bioactivity-guided isolation strategies, and to illustrate the mechanisms of
      action targeting on ethnomedical uses. Future clinical studies can also focus on
      the main therapeutic aspects, toxicity and adverse effects of B. chinensis.

PMID- 27032711
TI  - Exercise-Induced Systemic Venous Hypertension in the Fontan Circulation.
AB  - Increasingly end-organ injury is being demonstrated late after institution of the
      Fontan circulation, particularly liver fibrosis and cirrhosis. The exact
      mechanisms for these late phenomena remain largely elusive. Hypothesizing that
      exercise induces precipitous systemic venous hypertension and insufficient
      cardiac output for the exercise demand, that is, a possible mechanism for end
      organ injury, we sought to demonstrate the dynamic exercise responses in systemic
      venous perfusion (SVP) and concurrent end-organ perfusion. Ten stable Fontan
      patients and 9 control subjects underwent incremental cycle ergometry-based
      cardiopulmonary exercise testing. SVP was monitored in the right upper limb, and
      regional tissue oxygen saturation was monitored in the brain and kidney using
      near-infrared spectroscopy. SVP rose profoundly in concert with workload in the
      Fontan group, described by the regression equation 15.97 + 0.073 watts per mm Hg.
      In contrast, SVP did not change in healthy controls. Regional renal (p <0.01) and
      cerebral tissue saturations (p <0.001) were significantly lower and decrease more
      rapidly in Fontan patients. We conclude that in a stable group of adult patients
      with Fontan circulation, high-intensity exercise was associated with systemic
      venous hypertension and reduced systemic oxygen delivery. This physiological
      substrate has the potential to contribute to end-organ injury. 

PMID- 27032712
TI  - Effects of nutritional manipulation on body composition in the developing
      marsupial, Macropus eugenii.
AB  - When 60-day-old tammar wallaby pouch young (Macropus eugenii) are fostered to
      mothers at 120 days of lactation, their growth, developmental rate and maturation
      of their GH/IGF axes are markedly accelerated. To determine the effect of
      fostering on energy intake, body composition and fat accretion, we first measured
      total body fat and lean mass in these young. Next, we mimicked the triglyceride
      oleic and palmitic acid composition of 120-day milk by supplementing 60 day young
      with these fatty acids and comparing their growth with that of growth accelerated
      young. There was no difference in the weight or growth axis maturation of
      supplemented young but there was significantly more body fat in these and in the
      growth-accelerated fostered young than in controls. We conclude that the
      accelerated growth and GH/IGF axis maturation observed previously in fostered
      young is most likely due to increased milk consumption and earlier access to
      specific nutrients.

PMID- 27032713
TI  - A potential role of endoplasmic reticulum stress in development of ovarian
      hyperstimulation syndrome.
AB  - Vascular endothelial growth factor A (VEGFA) is crucial for ovarian angiogenesis,
      but its excess production induces ovarian hyperstimulation syndrome (OHSS). The
      aim of this study was to determine whether endoplasmic reticulum (ER) stress
      regulates VEGFA expression in granulosa cells, and whether its activation is
      involved in OHSS development. The expression of the spliced form of X-box-binding
      protein 1 [XBP1(S)], induced by ER stress, in cumulus cells from OHSS patients
      was higher than that in cumulus cells from non-OHSS patients. The ER stress
      inducer tunicamycin increased human chorionic gonadotropin-induced VEGFA
      production in human granulosa cells through the induction of XBP1(S), and
      pretreatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA)
      abrogated the effect of tunicamycin. In OHSS model rats, TUDCA administration
      prevented the OHSS development, reducing ovarian VEGFA production. Our findings
      suggest ER stress upregulates hCG-induced VEGFA production in granulosa cells,
      indicating that ER stress might be involved in OHSS development.

PMID- 27032716
TI  - Foreword.

PMID- 27032715
TI  - The impact of microgravity on bone in humans.
AB  - Experiencing real weightlessness in space is a dream for many of us who are
      interested in space research. Although space traveling fascinates us, it can
      cause both short-term and long-term health problems. Microgravity is the most
      important influence on the human organism in space. The human body undergoes
      dramatic changes during a long-term spaceflight. In this review, we will mainly
      focus on changes in calcium, sodium and bone metabolism of space travelers.
      Moreover, we report on the current knowledge on the mechanisms of bone loss in
      space, available models to simulate the effects of microgravity on bone on Earth
      as well as the combined effects of microgravity and cosmic radiation on bone. The
      available countermeasures applied in space will also be evaluated.

PMID- 27032714
TI  - Admixture mapping of serum vitamin D and parathyroid hormone concentrations in
      the African American-Diabetes Heart Study.
AB  - Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between
      individuals of African and European descent and may play a role in observed
      racial differences in bone mineral density (BMD). These findings suggest that
      mapping by admixture linkage disequilibrium (MALD) may be informative for
      identifying genetic variants contributing to these ethnic disparities. Admixture
      mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D,
      vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations
      and computed tomography measured thoracic and lumbar vertebral volumetric BMD in
      552 unrelated African Americans with type 2 diabetes from the African American
      Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry
      informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1,
      or 2 copies of a European-derived allele was determined. Non-parametric linkage
      analysis was performed by testing for association between each AIM using these
      probabilities among phenotypes, accounting for global ancestry, age, and gender.
      Fine-mapping of MALD peaks was facilitated by genome-wide association study
      (GWAS) data. VDBP levels were significantly linked in proximity to the protein
      coding locus (rs7689609, LOD=11.05). Two loci exhibited significant linkage
      signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD=3.20) and 12q13.2
      (rs11171526, LOD=3.10). iPTH was significantly linked on 9q31.3 (rs7854368,
      LOD=3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with
      VDBP, P=1.38*10(-82)) and novel (rs12741813 and rs10863774 with VDBP, P<6.43*10(
      5)) loci with plausible biological roles. Admixture mapping in combination with
      fine-mapping has focused efforts to identify loci contributing to ethnic
      differences in vitamin D-related traits.

PMID- 27032717
TI  - Foreword.

PMID- 27032718
TI  - Attributable fractions, modifiable risk factors and risk stratification using a
      risk score for peri-implant pathology.
AB  - PURPOSE: This study aimed to estimate the impact of risk factors for peri-implant
      pathology, to identify potentially modifiable factors, and to evaluate the
      accuracy of the risk algorithm, risk scores and risk stratification. METHODS:
      This retrospective case-control study with 1275 patients (255 cases; 1020
      controls) retrieved a model according to the predictors: history of
      Periodontitis, bacterial plaque, bleeding, bone level, lack of passive fit or non
      optimal screw joint, metal-ceramic restoration, proximity to other
      implants/teeth, and smoking habits. Outcome measures were the attributable
      fraction; the positive and negative likelihood ratios at different disease cut
      off points illustrated by the area under the curve statistic. RESULTS: Six
      predictors may be modified or controlled directly by either the patient or the
      clinician, accounting for a reduction in up to 95% of the peri-implant pathology
      cases. The positive and negative likelihood ratios were 9.69 and 0.13,
      respectively; the area under the curve was 0.96; a risk score was developed,
      making the complex statistical model useful to clinicians. CONCLUSIONS: Based on
      the results, six predictors for the incidence of peri-implant pathology can be
      modified to significantly improve the outcome. It was possible to stratify
      patients per risk category according to the risk score, providing a tool for
      clinicians to support their decision-making process.

PMID- 27032719
TI  - Barriers to Adoption of Mineralocorticoid Receptor Antagonists in Patients With
      Heart Failure: A Mixed-Methods Study.
AB  - BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are the most
      underutilized pharmacotherapy for heart failure. Minimal data are available on
      the barriers to MRA adoption from the perspective of prescribing clinicians.
      METHODS AND RESULTS: A mixed-methods study consisting of a survey (n=50), focus
      groups (n=39), interviews (n=6) with clinicians at a single US Department of
      Veterans Affairs medical center served to ascertain barriers to optimal use of
      MRAs. Participants were drawn from 6 groups: cardiology providers, cardiology
      fellows, hospitalists, clinical pharmacists, internal medicine residents, and
      primary care providers. Qualitative data were iteratively coded with qualitative
      data analysis software. The survey response rate was 17.3%. Overall, 51% of
      survey respondents were unfamiliar with eplerenone, and 6% were unfamiliar with
      spironolactone. In addition, 30% of respondents reported that they would order a
      laboratory test >2 weeks after a new MRA prescription, although that is beyond
      the guideline recommendation. Most providers correctly identified New York Heart
      Association class 3 and 4 patients as MRA eligible, but only 42% identified class
      2 patients as MRA eligible. Through analysis of focus groups, we identified 8
      barriers to MRA use in 3 categories: patient-based barriers (concerns about
      polypharmacy and comorbidities, adverse effects, perceived patient nonadherence),
      provider-based barriers (unclear roles and responsibilities, coordination and
      transitions of care, lack of experience or familiarity with MRAs), and system
      based barriers (system overload and provider time constraints, lack of systematic
      follow-up procedures). CONCLUSIONS: Eight primary barriers to MRA adoption at the
      provider, patient, and health system levels were identified from the prescriber
      perspective. These barriers can inform the creation of multilevel interventions
      that will be required to close the gap in MRA adoption.

PMID- 27032720
TI  - Bilateral areolar sebaceous hyperplasia in a post-menopausal woman.

PMID- 27032722
TI  - Effect of xylitol varnishes on remineralization of artificial enamel caries
      lesions in situ.
AB  - OBJECTIVES: Analyze the effect of varnishes containing xylitol compared to
      commercial fluoridated varnishes on the remineralization of artificial enamel
      caries lesions in situ. METHODS: Twenty subjects took part in this crossover,
      double-blind study performed in four phases of 5days each. Each subject worn
      palatal appliances containing four predemineralized bovine enamel specimens.
      Artificial caries lesions were produced by immersion in 30ml of lactic acid
      buffer containing 3mM CaCl2.2H2O, 3mM KH2PO4, 6MUM tetraetil metil diphosphanate
      (pH 5.0) for 6days. The specimens in each subject were treated once with the
      following varnishes: 20% xylitol (experimental); DuofluoridTM (6% NaF, 6% CaF2),
      DuraphatTM (5% NaF, positive control) and placebo (no-F/xylitol, negative
      control). The varnishes were applied in a thin layer and removed after 6h.
      Fifteen subjects were able to finish all phases. The enamel alterations were
      quantified by surface hardness and transversal microradiography. The percentage
      of surface hardness recovery (%SHR), the integrated mineral loss and lesion depth
      were statistically analyzed by Friedmann and Dunn's tests test (p<0.05). RESULTS:
      Enamel surface remineralization was significantly increased by DuraphatTM,
      DuofluoridTM and 20% xylitol formulations. Significant subsurface mineral
      remineralization could also be seen for the experimental and commercial
      varnishes, except for DuraphatTM, when the parameter "lesion depth" was
      considered. CONCLUSIONS: 20% xylitol varnish seem to be a promising alternative
      to increase surface and subsurface remineralization of artificial caries lesions
      in situ. CLINICAL SIGNIFICANCE: effective vehicles are desirable for caries
      control. Xylitol varnishes seem to be promising alternatives to increase enamel
      remineralization in situ, which should be confirmed by clinical studies.

PMID- 27032721
TI  - Human neural progenitors differentiate into astrocytes and protect motor neurons
      in aging rats.
AB  - Age-associated health decline presents a significant challenge to healthcare,
      although there are few animal models that can be used to test potential
      treatments. Here, we show that there is a significant reduction in both spinal
      cord motor neurons and motor function over time in the aging rat. One explanation
      for this motor neuron loss could be reduced support from surrounding aging
      astrocytes. Indeed, we have previously shown using in vitro models that aging rat
      astrocytes are less supportive to rat motor neuron function and survival over
      time. Here, we test whether rejuvenating the astrocyte niche can improve the
      survival of motor neurons in an aging spinal cord. We transplanted fetal-derived
      human neural progenitor cells (hNPCs) into the aging rat spinal cord and found
      that the cells survive and differentiate into astrocytes with a much higher
      efficiency than when transplanted into younger animals, suggesting that the aging
      environment stimulates astrocyte maturation. Importantly, the engrafted
      astrocytes were able to protect against motor neuron loss associated with aging,
      although this did not result in an increase in motor function based on behavioral
      assays. We also transplanted hNPCs genetically modified to secrete glial cell
      line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this
      combination of cell and protein delivery can protect motor neurons in animal
      models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons,
      though to the same extent as hNPCs alone, and again had no effect on motor
      function. We conclude that hNPCs can survive well in the aging spinal cord,
      protect motor neurons and mature faster into astrocytes when compared to
      transplantation into the young spinal cord. While there was no functional
      improvement, there were no functional deficits either, further supporting a good
      safety profile of hNPC transplantation even into the older patient population.

PMID- 27032723
TI  - PSA Abstracts.

PMID- 27032724
TI  - Functional neuroanatomy of meditation: A review and meta-analysis of 78
      functional neuroimaging investigations.
AB  - Meditation is a family of mental practices that encompasses a wide array of
      techniques employing distinctive mental strategies. We systematically reviewed 78
      functional neuroimaging (fMRI and PET) studies of meditation, and used activation
      likelihood estimation to meta-analyze 257 peak foci from 31 experiments involving
      527 participants. We found reliably dissociable patterns of brain activation and
      deactivation for four common styles of meditation (focused attention, mantra
      recitation, open monitoring, and compassion/loving-kindness), and suggestive
      differences for three others (visualization, sense-withdrawal, and non-dual
      awareness practices). Overall, dissociable activation patterns are congruent with
      the psychological and behavioral aims of each practice. Some brain areas are
      recruited consistently across multiple techniques-including insula,
      pre/supplementary motor cortices, dorsal anterior cingulate cortex, and
      frontopolar cortex-but convergence is the exception rather than the rule. A
      preliminary effect-size meta-analysis found medium effects for both activations
      (d=0.59) and deactivations (d=-0.74), suggesting potential practical
      significance. Our meta-analysis supports the neurophysiological dissociability of
      meditation practices, but also raises many methodological concerns and suggests
      avenues for future research.

PMID- 27032725
TI  - Measurements of air dose rates in and around houses in the Fukushima Prefecture
      in Japan after the Fukushima accident.
AB  - Measurements of air dose rates for 192 houses in a less contaminated area (<0.5
      MUSv h-1) of the Fukushima Prefecture in Japan were conducted in both living
      rooms and/or bedrooms using optically stimulated luminescence (OSL) dosimeters
      and around the houses via a man-borne survey at intervals of several meters. The
      relation of the two air dose rates (inside and outside) for each house, including
      the background from natural radionuclides, was divided into several categories,
      determined by construction materials (light and heavy) and floor number, with the
      dose reduction factors being expressed as the ratio of the dose inside to that
      outside the house. For wooden and lightweight steel houses (classed as light),
      the dose rates inside and outside the houses showed a positive correlation and
      linear regression with a slope-intercept form due to the natural background,
      although the degree of correlation was not very high. The regression coefficient,
      i.e., the average dose reduction factor, was 0.38 on the first floor and 0.49 on
      the second floor. It was found that the contribution of natural radiation cannot
      be neglected when we consider dose reduction factors in less contaminated areas.
      The reductions in indoor dose rates are observed because a patch of ground under
      each house is not contaminated (this is the so-called uncontaminated effect)
      since the shielding capability of light construction materials is typically low.
      For reinforced steel-framed concrete houses (classed as heavy), the dose rates
      inside the houses did not show a correlation with those outside the houses due to
      the substantial shielding capability of these materials. The average indoor dose
      rates were slightly higher than the arithmetic mean value of the outdoor dose
      rates from the natural background because concrete acts as a source of natural
      radionuclides. The characteristics of the uncontaminated effect were clarified
      through Monte Carlo simulations. It was found that there is a great variation in
      air dose rates even within one house, depending on the height of the area and its
      closeness to the outside boundary. Measurements of outdoor dose rates required
      consideration of local variations depending on the environment surrounding each
      house. The representative value was obtained from detailed distributions of air
      dose rates around the house, as measured by a man-borne survey. Therefore, it is
      imperative to recognize that dose reduction factors fluctuate in response to
      various factors such as the size and shape of a house, construction materials
      acting as a shield and as sources, position (including height) within a room,
      floor number, total number of floors, and surrounding environment.

PMID- 27032726
TI  - Erratum.

PMID- 27032727
TI  - Erratum.

PMID- 27032728
TI  - Erratum.

PMID- 27032729
TI  - Erratum.

PMID- 27032730
TI  - Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static
      Networks.
AB  - Engineered tissues need a vascular network to supply cells with nutrients and
      oxygen after implantation. A network that can connect to the vasculature of the
      patient after implantation can be included during in vitro culture. For optimal
      integration, this network needs to be highly organized, including venules,
      capillaries, and arterioles, to supply all of the cells with sufficient
      nutrients. Owing to the importance of vascularization for the clinical
      applicability of tissue engineering, many approaches have been investigated to
      include an organized vascular network in tissue constructs. This review will give
      an overview of recent efforts, and will propose future perspectives to engineer
      the optimal, functional vascular network.

PMID- 27032733
TI  - Listening.

PMID- 27032732
TI  - Subpubic Cartilaginous Cyst: A Rare Sub-Clitoral Mass.

PMID- 27032734
TI  - Timing of Excessive Weight Gain During Pregnancy Modulates Newborn Anthropometry.
AB  - OBJECTIVE: Excessive gestational weight gain (GWG) is associated with increased
      birth weight and neonatal adiposity. However, timing of excessive GWG may have a
      differential impact on birth outcomes. The objective of this study was to compare
      the effect of early and mid/late excessive GWG on newborn anthropometry in the
      context of the Canadian clinical recommendations that are specific for first
      trimester and for second/third trimesters based on maternal pre-pregnancy BMI.
      METHODS: We included 607 glucose-tolerant women in our main analyses, after
      excluding women who had less than the recommended total GWG. Maternal body weight
      was measured in early pregnancy, mid-pregnancy, and late pregnancy. Maternal and
      fetal clinical outcomes were collected, including newborn anthropometry. Women
      were divided into four groups according to the Canadian guidelines for GWG in the
      first and in the second/third trimesters: (1) "overall non-excessive" (reference
      group); (2) "early excessive GWG"; (3) "mid/late excessive GWG"; and (4) "overall
      excessive GWG." Differences in newborn anthropometry were tested across GWG
      categories. RESULTS: Women had a mean (+/-SD) pre-pregnancy BMI of 24.7 +/- 5.2
      kg/m(2) and total GWG of 15.3 +/- 4.4 kg. Women with mid/late excessive GWG gave
      birth to heavier babies (gestational age-adjusted birth weight z-score 0.33 +/-
      0.91) compared with women in the reference group (0.00 +/- 0.77, P = 0.007),
      whereas women with early excessive GWG gave birth to babies of similar weight
      (gestational age-adjusted z-score 0.01 +/- 0.86) to the reference group (0.00 +/-
      0.77, P = 0.84). When we stratified our analyses and investigated women who
      gained within the recommendations for total GWG, mid/late excessive GWG
      specifically was associated with greater newborn size, similar to our main
      analyses. CONCLUSION: Excessive GWG in mid/late pregnancy in women who did not
      gain weight excessively in early pregnancy is associated with increased birth
      size, even in those who gained within the Canadian recommendations for total GWG.

PMID- 27032735
TI  - Delivery at Term: Impact of University Education by Week of Gestation.
AB  - OBJECTIVE: Data on risk factors for early term delivery are scant despite greater
      complications in infants born at 37 and 38 weeks' gestation. We determined the
      probability of delivery by gestational week at term according to level of
      maternal education, an established risk factor for preterm birth. METHODS: We
      analyzed 2 319 697 live singleton births at term (>=37 weeks) in Quebec from 1981
      to 2010. We estimated hazard ratios with 95% confidence intervals (CI) of
      delivery according to level of maternal education, adjusting for individual
      characteristics. The main outcome measure was the probability of delivery at term
      by week of gestation for women with university education versus high school
      education. RESULTS: Early term birth at 37 and 38 weeks of gestation was less
      common for university-educated women (23.1%) than for high school-educated women
      (25.8%; P < 0.001). Compared with women with a high school education, university
      educated women had a 15% lower probability of delivery at 37 to 38 weeks (95% CI:
      0.84 to 0.86), a 4% lower probability of delivery at 39 weeks (95% CI: 0.96 to
      0.97) and a 2% lower probability of delivery at 40 weeks (95% CI: 0.97 to 0.98).
      University-educated women were, however, more likely to deliver at 41 weeks.
      CONCLUSION: A higher level of education was associated with longer duration of
      pregnancy at term. Women who were university-educated had a lower chance of
      delivery at 37, 38, 39, and even 40 weeks of gestation. Clinicians should be
      aware that women with lower levels of education are more likely to deliver
      earlier at term.

PMID- 27032736
TI  - Acuity Assessment in Obstetrical Triage.
AB  - OBJECTIVE: A five-category Obstetrical Triage Acuity Scale (OTAS) was developed
      with a comprehensive set of obstetrical determinants. The purposes of this study
      were: (1) to compare the inter-rater reliability (IRR) in tertiary and community
      hospital settings and measure the intra-rater reliability (ITR) of OTAS; (2) to
      establish the validity of OTAS; and (3) to present the first revision of OTAS
      from the National Obstetrical Triage Working Group. METHODS: To assess IRR,
      obstetrical triage nurses were randomly selected from London Health Sciences
      Centre (LHSC) (n = 8), Stratford General Hospital (n = 11), and Chatham General
      Hospital (n= 7) to assign acuity levels to clinical scenarios based on actual
      patient visits. At LHSC, a group of nurses were retested at nine months to
      measure ITR. To assess validity, OTAS acuity level was correlated with measures
      of resource utilization. RESULTS: OTAS has significant and comparable IRR in a
      tertiary care hospital and in two community hospitals. Repeat assessment in a
      cohort of nurses demonstrated significant ITR. Acuity level correlated
      significantly with performance of routine and second order laboratory
      investigations, point of care ultrasound, nursing work load, and health care
      provider attendance. A National Obstetrical Triage Working Group was formed and
      guided the first revision. Four acuity modifiers were added based on
      hemodynamics, respiratory distress, cervical dilatation, and fetal well-being.
      CONCLUSION: OTAS is the first obstetrical triage scale with established
      reliability and validity. OTAS enables standardized assessments of acuity within
      and across institutions. Further, it facilitates assessment of patient care and
      flow based on acuity.

PMID- 27032737
TI  - Ultrasound Assessment of Lower Uterine Segment Thickness During Pregnancy,
      Labour, and the Postpartum Period.
AB  - OBJECTIVES: To evaluate the normal ranges of lower uterine segment (LUS)
      thickness throughout pregnancy in women without a previous cesarean and to
      evaluate the relationship between ultrasound and intraoperative LUS thickness.
      METHODS: We assessed LUS thickness using transabdominal and transperineal
      longitudinal scan at each week of gestation, during labour, and in the postpartum
      period in 1000 pregnant women without previous CS. Secondly, we assessed LUS
      thickness immediately before CS (using ultrasound) and intraoperatively (using
      ophthalmic calipers) immediately before delivery of the fetus in 35 women with a
      previous CS and 29 women without previous CS undergoing elective CS before
      labour. RESULTS: We performed 20 307 LUS thickness measurements in between 119
      and 944 women at each week of gestation, in 944 women during labour, and in 936
      women after delivery. We observed a strong relationship between transabdominal
      and transperineal ultrasound (P < 0.001) and an inverse correlation between LUS
      thickness and gestational age (P < 0.001), with a mean thickness of 5.1 +/- 1.4
      mm at 20 weeks, 3.6 +/- 1.3 mm at 30 weeks, and 2.3 +/- 0.6 mm at 40 weeks of
      gestation. In women undergoing elective CS, we observed a strong relationship
      between antepartum and intraoperative LUS thickness (P < 0.001), with mean
      thicknesses of 2.2 +/- 0.7 mm in 28 women without thinning of LUS; 0.8 +/- 0.1 mm
      in four women with grade II uterine scar dehiscence; and 0.4 +/- 0.1 mm in three
      women with grade III dehiscence. A LUS myometrial thickness less than 1.2 mm
      could have predicted all grade II and grade III uterine scar dehiscences without
      false-positive cases. CONCLUSION: LUS thickness decreases with gestational age
      and correlates strongly with the intraoperative LUS thickness in women with a
      previous CS.

PMID- 27032738
TI  - Increasing Minimally Invasive Hysterectomy: A Canadian Academic Health Centre
      Experience.
AB  - OBJECTIVE: An institution wide strategic plan was established to improve
      minimally invasive surgery (MIS) across all surgical divisions at The Ottawa
      Hospital (TOH). The primary objective of this study is to determine the change in
      MIS hysterectomy rate between 2005 and 2012 at this centre. Secondary objectives
      include determining the impact on overall length of stay (LOS) in hospital,
      complications, return to hospital, operating room time, and cost. METHODS: We
      performed a retrospective analysis of all hysterectomies for benign disease
      performed at TOH between 2005 and 2012. Cases were excluded if they were related
      to pregnancy or classified as "partial hysterectomy." The outcomes and cost of
      the approaches were compared. RESULTS: A total of 4337 hysterectomy cases were
      reviewed. The MIS hysterectomy rate increased from 40.1% in 2005 to 74.2% in
      2012. There was a decrease in mean LOS from 2.5 to 1.6 days. This translated to a
      saving of 1898 inpatient bed days. Compared with laparotomy, laparoscopic
      hysterectomy was associated with a reduced risk of transfusion and a reduced risk
      of ileus, and vaginal hysterectomy was associated with an increased risk of
      postoperative abscess. There was no difference in rates of returning to hospital
      or other complications between women undergoing abdominal hysterectomy and women
      undergoing MIS hysterectomy (which included both laparoscopic and vaginal
      approaches). The mean (SD) cost per approach was $7241 ($1985), $4532 ($1718),
      and $5637 ($1579) for abdominal hysterectomy, vaginal hysterectomy, and
      laparoscopic hysterectomy, respectively. CONCLUSION: The initiatives implemented
      at TOH in 2007 resulted in a significant increase in the MIS hysterectomy rate, a
      decrease in mean LOS, and substantial theoretical cost savings for the hospital.

PMID- 27032739
TI  - Analgesia for Medically Induced Second Trimester Termination of Pregnancy: A
      Randomized Trial.
AB  - OBJECTIVE: To compare the efficacy between intravenous patient-controlled
      analgesia (IVPCA) and patient-controlled epidural analgesia (PCEA) in women
      undergoing medically induced second trimester termination of pregnancy (TOP).
      METHODS: We conducted a randomized trial in a Canadian quaternary care hospital.
      We included in the study women of gestational age 12 weeks to 23+6 weeks who were
      undergoing second trimester induction of labour between June 2012 and January
      2014. Participants were computer-randomized to receive either IVPCA with fentanyl
      or PCEA with bupivacaine and fentanyl, with the option to cross over between
      treatment groups. We administered Quality of Recovery-40 (QoR-40) questionnaires
      pre-procedure, at the time of discharge, and 24 hours after discharge. Pain
      scores, satisfaction scores, and obstetrical complications also were noted.
      RESULTS: One hundred thirty-eight women were approached for participation in the
      study; 80 declined and 16 were ineligible, leaving 42 participants. Three women
      subsequently withdrew consent, and two were not included in the results because
      of protocol violations. A total of 37 women completed the study. Twenty (54%)
      were allocated to the IVPCA group and 17 (46%) to the PCEA group. Although the
      QoR-40 values at the time of discharge and at 24 hours after discharge were
      significantly higher in the PCEA group, they also were significantly higher
      before the procedure in that group. The within-group differences in QoR-40
      (between QoR-40 at discharge and QoR pre-procedure, and between QoR-40 at 24
      hours after discharge and QoR pre-procedure), maximum pain scores, satisfaction,
      and obstetrical complication rates did not differ significantly between the two
      groups. CONCLUSION: IVPCA and PCEA provide similar quality of recovery, quality
      of analgesia, and satisfaction for women undergoing second trimester TOP.

PMID- 27032740
TI  - Abdominal Wall Pain in Women With Chronic Pelvic Pain.
AB  - OBJECTIVE: To investigate the role of abdominal wall pain (AWP) in women with
      pelvic pain. METHODS: We conducted a retrospective review of consecutive patients
      with pelvic pain seen in a tertiary referral centre between January and December
      2012. AWP was defined as abdominal wall tenderness with a positive Carnett test
      (i.e., tenderness that worsened or remained the same with abdominal wall
      contraction). Pairwise comparisons were carried out between clinical variables
      (e.g., chronic pelvic pain) and AWP. This was followed by multiple logistic
      regression to identify the clinical variables with an independent association
      with AWP. RESULTS: The prevalence of AWP in women with pelvic pain was 67%
      (127/190). On multiple logistic regression, AWP was independently associated with
      chronic pelvic pain (OR 13.8; 95% CI 3.71 to 51.2, P < 0.001), but not with other
      symptoms including dysmenorrhea, deep and superficial dyspareunia, or bowel and
      bladder symptomology. In a corollary analysis, women with AWP were more likely to
      require opioids or pain adjuvants than women without AWP (P = 0.015 and P <
      0.001). CONCLUSION: AWP is common in women with pelvic pain and may contribute
      specifically to the symptom of chronic pelvic pain.

PMID- 27032741
TI  - Management of Labour and Delivery in a Patient With Acquired Factor VII
      Deficiency With Inhibitor: A Case Report.
AB  - BACKGROUND: Acquired factor VII (FVII) deficiency with inhibitor increases the
      risk of hemorrhage during pregnancy. However, there are no published reports
      guiding its management in the peripartum period. CASE: A 24-year-old woman with
      inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was
      administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no
      bleeding-related complications; however, the FVII level was supratherapeutic. The
      patient returned during a second pregnancy. A reduced dose of rFVIIa was
      administered. The delivery was complicated by postpartum hemorrhage, which
      resolved with the addition of uterotonic agents. CONCLUSION: Recombinant FVIIa
      and tranexamic acid offer an effective peripartum treatment in women with
      inhibitory antibody to FVII. Further research should delineate the optimal time
      of administration.

PMID- 27032742
TI  - The Investigations Required Before Referring a Patient to a Gynaecologic
      Oncologist.
AB  - OBJECTIVE: To provide guidance for referring physicians regarding what
      gynaecologic oncologists want and do not require in the referral package for a
      new patient. METHODS: An email survey was circulated to all members of the
      Society of Gynecologic Oncology of Canada (GOC) asking what they felt was
      required in a new patient referral package so that they could provide a timely
      consultation and management plan. RESULTS: The survey had a 79% response rate
      among 121 GOC members. Before referral of patients with endometrial cancer, 50%
      of respondents did not want additional investigations; only 4% wanted an MRI
      performed prior to them seeing the patient. For patients with high-grade cancers
      of the uterus (including serous), 40% wanted to see the patient without further
      investigations, while 42% wanted a CT scan report to be included in the referral
      package. For patients with cervical cancer, 56% of respondents wanted to see the
      patient without any further investigations, while 24% wished to have an MRI
      report included in the referral package. For patients with vulvar cancer, 50% of
      respondents did not want any further investigations; for patients with a pelvic
      mass, the majority of respondents wanted a serum CA 125 level in the referral
      package, while 0% to 3% only wanted an MRI. The preferred modality for imaging of
      the chest was a chest X-ray only. CONCLUSION: Our survey indicated that
      gynaecologic oncologists want little information in the referral package beyond
      the biopsy result. MRI is not required in the workup of most patients with a
      pelvic mass or uterine cancer.

PMID- 27032743
TI  - Implementation of an Interprofessional Team Review of Adverse Events in
      Obstetrics Using a Standardized Computer Tool: A Mixed Methods Study.
AB  - OBJECTIVE: As part of a larger study, an interprofessional team piloted a
      computer tool called Standardized Clinical Outcome Review (SCOR) to review
      adverse obstetric events that occurred at a tertiary care hospital over a 12
      month period. We sought to understand whether the SCOR tool offered a feasible,
      acceptable, and appropriate strategy for improving patient safety through
      improved review of incidents. METHODS: We designed a mixed methods implementation
      study. Following completion of the 12-month pilot period, team members completed
      a questionnaire and participated in a focus group. Quantitative data analysis was
      performed using descriptive statistics, and qualitative data were analyzed using
      grounded theory to generate themes. RESULTS: The SCOR tool was easy to implement
      with an interprofessional team. Despite technical challenges with the software,
      the tool was quicker and more efficient than traditional case review methods. The
      content was appropriate for an obstetric unit and provided objective
      identification of factors contributing to adverse events. Team members were
      positive about the use of the tool in their institution and in wider contexts and
      believed that it was a valuable tool for raising awareness and addressing patient
      safety at their unit. CONCLUSIONS: SCOR was an acceptable and appropriate tool
      for the interprofessional team review of adverse outcomes, and its use represents
      a significant advance in the quality assurance process for formal peer review of
      incidents.

PMID- 27032744
TI  - Exercise During Pregnancy: Current Recommendations by Canadian Maternity Health
      Care Providers.

PMID- 27032745
TI  - Rural Perinatal Surgical Services: Time for an Alliance Between Providers.

PMID- 27032747
TI  - [Smoking and electronic cigarettes in France].
AB  - France is one of the developed countries where the prevalence of tobacco use is
      the highest. The reduction of incidence and prevalence of tobacco use in the near
      future would considerably decrease tobacco associated mortality and morbidity.
      The electronic cigarette, a consumer product that delivers pharmacologically
      active substances, is used by several millions of persons in France. The benefit
      risk ratio of electronic cigarette use is unknown, as of today.

PMID- 27032746
TI  - Canadian Contraception Consensus (Part 3 of 4): Chapter 7--Intrauterine
      Contraception.
AB  - OBJECTIVE: To provide guidelines for health care providers on the use of
      contraceptive methods to prevent pregnancy and on the promotion of healthy
      sexuality. OUTCOMES: Overall efficacy of cited contraceptive methods, assessing
      reduction in pregnancy rate, safety, ease of use, and side effects; the effect of
      cited contraceptive methods on sexual health and general well-being; and the
      relative cost and availability of cited contraceptive methods in Canada.
      EVIDENCE: Published literature was retrieved through searches of Medline and The
      Cochrane Database from January 1994 to January 2015 using appropriate controlled
      vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g.,
      contraception, family planning, hormonal contraception, emergency contraception).
      Results were restricted to systematic reviews, randomized control
      trials/controlled clinical trials, and observational studies published in English
      from January 1994 to January 2015. Searches were updated on a regular basis in
      incorporated in the guideline to June 2015. Grey (unpublished) literature was
      identified through searching the websites of health technology assessment and
      health technology-related agencies, clinical practice guideline collections,
      clinical trial registries, and national and international medical specialty
      societies. VALUES: The quality of the evidence in this document was rated using
      the criteria described in the Report of the Canadian Task Force on Preventive
      Health Care (Table 1). CHAPTER 7: INTRAUTERINE CONTRACEPTION: SUMMARY STATEMENTS:
      1. Intrauterine contraceptives are as effective as permanent contraception
      methods. (II-2) 2. The use of levonorgestrel-releasing intrauterine system (LNG
      IUS) 52 mg by patients taking tamoxifen is not associated with recurrence of
      breast cancer. (I) 3. Intrauterine contraceptives have a number of
      noncontraceptive benefits. The levonorgestrel-releasing intrauterine system (LNG
      IUS) 52 mg significantly decreases menstrual blood loss (I) and dysmenorrhea. (II
      2) Both the copper intrauterine device and the LNG-IUS significantly decrease the
      risk of endometrial cancer. (II-2) 4. The risk of uterine perforation decreases
      with inserter experience but is higher in postpartum and breastfeeding women. (II
      2) 5. The risk of pelvic inflammatory disease (PID) is increased slightly in the
      first month after intrauterine contraceptive (IUC) insertion, but the absolute
      risk is low. Exposure to sexually transmitted infections and not the IUC itself
      is responsible for PID occurring after the first month of use. (II-2) 6.
      Nulliparity is not associated with an increased risk of intrauterine
      contraceptive expulsion. (II-2) 7. Ectopic pregnancy with an intrauterine
      contraceptive (IUC) is rare, but when a pregnancy occurs with an IUC in situ, it
      is an ectopic pregnancy in 15% to 50% of the cases. (II-2) 8. In women who
      conceive with an intrauterine contraceptive (IUC) in place, early IUC removal
      improves outcomes but does not entirely eliminate risks. (II-2) 9. Intrauterine
      contraceptives do not increase the risk of infertility. (II-2) 10. Immediate
      insertion of an intrauterine contraceptive (10 minutes postplacental to 48 hours)
      postpartum or post-Caesarean section is associated with a higher continuation
      rate compared with insertion at 6 weeks postpartum. (I) 11. Immediate insertion
      of an intrauterine contraceptive (IUC; 10 minutes postplacental to 48 hours)
      postpartum or post-Caesarean section is associated with a higher risk of
      expulsion. (I) The benefit of inserting an IUC immediately postpartum or post
      Caesarean section outweighs the disadvantages of increased risk of perforation
      and expulsion. (II-C) 12. Insertion of an intrauterine contraceptive in
      breastfeeding women is associated with a higher risk of uterine perforation in
      the first postpartum year. (II-2) 13. Immediate insertion of an intrauterine
      contraceptive (IUC) post-abortion significantly reduces the risk of repeat
      abortion (II-2) and increases IUC continuation rates at 6 months. (I) 14.
      Antibiotic prophylaxis for intrauterine contraceptive insertion does not
      significantly reduce postinsertion pelvic infection. (I) RECOMMENDATIONS: 1.
      Health care professionals should be careful not to restrict access to
      intrauterine contraceptives (IUC) owing to theoretical or unproven risks. (III-A)
      Health care professionals should offer IUCs as a first-line method of
      contraception to both nulliparous and multiparous women. (II-2A) 2. In women
      seeking intrauterine contraception (IUC) and presenting with heavy menstrual
      bleeding and/or dysmenorrhea, health care professionals should consider the use
      of the levonorgestrel intrauterine system 52 mg over other IUCs. (I-A) 3.
      Patients with breast cancer taking tamoxifen may consider a levonorgestrel
      releasing intrauterine system 52 mg after consultation with their oncologist. (I
      A) 4. Women requesting a levonorgestrel-releasing intrauterine system or a copper
      intrauterine device should be counseled regarding changes in bleeding patterns,
      sexually transmitted infection risk, and duration of use. (III-A) 5. A health
      care professional should be reasonably certain that the woman is not pregnant
      prior to inserting an intrauterine contraceptive at any time during the menstrual
      cycle. (III-A) 6. Health care providers should consider inserting an intrauterine
      contraceptive immediately after an induced abortion rather than waiting for an
      interval insertion. (I-B) 7. In women who conceive with an intrauterine
      contraceptive (IUC) in place, the diagnosis of ectopic pregnancy should be
      excluded as arly as possible. (II-2A) Once an ectopic pregnancy has been
      excluded, the IUC should be removed without an invasive procedure. The IUC may be
      removed at the time of a surgical termination. (II-2B) 8. In the case of pelvic
      inflammatory disease, it is not necessary to remove the intrauterine
      contraceptive unless there is no clinical improvement after 48 to 72 hours of
      appropriate antibiotic treatment. (II-2B) 9. Routine antibiotic prophylaxis for
      intrauterine contraceptive (IUC) insertion is not indicated. (I-B) Health care
      providers should perform sexually transmitted infection (STI) testing in women at
      high risk of STI at the time of IUC insertion. If the test is positive for
      chlamydia and/or gonorrhea, the woman should be appropriately treated
      postinsertion and the IUC can remain in situ. (II-2B) 10. Unscheduled bleeding in
      intrauterine contraception users, when persistent or associated with pelvic pain,
      should be investigated to rule out infection, pregnancy, gynecological pathology,
      expulsion or malposition. (III-A)

PMID- 27032748
TI  - The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the
      host cell.
AB  - AS1411 is a G-rich aptamer that forms a stable G-quadruplex structure and
      displays antineoplastic properties both in vitro and in vivo. This
      oligonucleotide has undergone phase 2 clinical trials. The major molecular target
      of AS1411 is nucleolin (NCL), a multifunctional nucleolar protein also present in
      the cell membrane where it selectively mediates the binding and uptake of AS1411.
      Cell-surface NCL has been recognised as a low-affinity co-receptor for human
      immunodeficiency virus type 1 (HIV-1) anchorage on target cells. Here we assessed
      the anti-HIV-1 properties and underlying mechanism of action of AS1411. The
      antiviral activity of AS1411 was determined towards different HIV-1 strains, host
      cells and at various times post-infection. Acutely, persistently and latently
      infected cells were tested, including HIV-1-infected peripheral blood mononuclear
      cells from a healthy donor. Mechanistic studies to exclude modes of action other
      than virus binding via NCL were performed. AS1411 efficiently inhibited HIV-1
      attachment/entry into the host cell. The aptamer displayed antiviral activity in
      the absence of cytotoxicity at the tested doses, therefore displaying a wide
      therapeutic window and favourable selectivity indexes. These findings, besides
      validating cell-surface-expressed NCL as an antiviral target, open the way for
      the possible use of AS1411 as a new potent and promisingly safe anti-HIV-1 agent.

PMID- 27032749
TI  - Lumbar paraganglioma.
AB  - Spinal paragangliomas (SP) are benign and overall rare extra-adrenal
      neuroendocrine tumors often diagnosed during workup for lower back pain. Complete
      surgical resection achieves both symptomatic relief and cure. We present a 32
      year-old man with a longstanding history of lumbago and bilateral lower extremity
      pain found to have a lumbar paraganglioma at the level of the L3 vertebrae. The
      clinical, histopathological, and radiological characteristics are described,
      including the rare finding of superficial siderosis on MRI of the brain. A
      laminectomy with microscopic dissection of the intradural mass achieved complete
      debulking without evidence of residual tumor. Excellent prognosis can be achieved
      with complete surgical resection of SP without the need for adjuvant therapy.
      Therefore, care should be taken to distinguish these spinal tumors from those
      that appear similar but are more aggressive. As such, the radiological finding of
      superficial siderosis should raise the suspicion for SP when a vascular
      intradural extramedullary spinal tumor is observed. 

PMID- 27032750
TI  - A Patient with Attention Deficit Hyperactivity Disorder and Hypertension.

PMID- 27032751
TI  - Phorbol 12-myristate 13-acetate promotes nuclear translocation of hepatic steroid
      response element binding protein-2.
AB  - Sterol regulatory element-binding protein (SREBP)-2 is a pivotal transcriptional
      factor in cholesterol metabolism. Factors interfering with the proper functioning
      of SREBP-2 potentially alter plasma lipid profiles. Phorbol 12-myristate 13
      acetate (PMA), which is a common protein kinase C (PKC) activator, was shown to
      promote the post-translational processing and nuclear translocation of SREBP-2 in
      hepatic cells in the current study. Following SREBP-2 translocation, the
      transcripts of its target genes HMGCR and LDLR were upregulated as demonstrated
      by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay.
      Electrophoretic mobility shift assays (EMSA) also demonstrated an induced DNA
      binding activity on the sterol response element (SRE) domain under PMA treatment.
      The increase of activated Srebp-2 without the concurrent induced mRNA expression
      was also observed in an animal model. As the expression of SREBP-2 was not
      increased by PMA, the activation of PKC was the focus of investigation. Specific
      PKC isozyme inhibition and overexpression supported that PKCbeta was responsible
      for the promoting effect. Further studies showed that the mitogen-activated
      protein kinases (MAPKs) extracellular signal-regulated kinases (ERK) and c-Jun N
      terminal kinases (JNK), but not 5' adenosine monophosphate-activated protein
      kinase (AMPK), were the possible downstream signaling proteins of PKCbeta. In
      conclusion, this study illustrated that PKCbeta increased SREBP-2 nuclear
      translocation in a pathway mediated by MEK/ERK and JNK, rather than the one
      dictated by AMPK. These results revealed a novel signaling target of PKCbeta in
      the liver cells.

PMID- 27032752
TI  - Bitter taste receptors: Extraoral roles in pathophysiology.
AB  - Over the past decade tremendous progress has been made in understanding the
      functional role of bitter taste receptors (T2Rs) and bitter taste perception.
      This review will cover the recent advances made in identifying the role of T2Rs
      in pathophysiological states. T2Rs are widely expressed in various parts of human
      anatomy and have been shown to be involved in physiology of respiratory system,
      gastrointestinal tract and endocrine system. Empirical evidence has shown T2Rs to
      be an integral component of antimicrobial immune responses in upper respiratory
      tract infections. The studies on human airway smooth muscle cells have shown that
      a potent bitter tastant induced bronchodilatory effects mediated by bitter taste
      receptors. Clinical data suggests a role for T2R38 polymorphism in predisposition
      of individuals to chronic rhinosinusitis. The role of genetic variation in T2Rs
      and its impact on disease susceptibility have been investigated in various other
      disease risk factors such as alcohol dependence, head and neck cancers.
      Preliminary reports have demonstrated differential expression of functional T2Rs
      in breast cancer cell lines. Studies on the role of T2Rs in pathophysiology of
      diseases including chronic rhinosinusitis, asthma, cystic fibrosis, and cancer
      have been promising. However, research in this field is in its nascent stages,
      and more confirmatory studies on animal models and in clinical settings are
      required.

PMID- 27032753
TI  - The surgical management of necrotising enterocolitis (NEC).
AB  - Necrotising enterocolitis (NEC) is a neonatal surgical emergency. At its early
      stages, the management of NEC is largely medical using broad-spectrum
      antibiotics, gut rest and total parental nutrition. The only absolute indication
      for surgery is an intra-abdominal perforation. There are several relative
      indications for surgery based on clinical, biochemical and radiological
      parameters. Once the decision to intervene is made, several approaches may be
      taken. Peritoneal lavage can be used as a salvage procedure or definitive
      management in some cases. The most common approach taken is bowel resection with
      enterostomy formation. There is a role for primary anastomosis of bowel in
      limited NEC. In severe, multi-focal NEC a high diverting jejunostomy or "clip and
      drop technique" can be used. Laparoscopy has a limited role and is not
      widespread. The surgical complications of NEC include stoma related morbidity,
      anastomotic leak/stricture and short-bowel syndrome. Long-term data on
      neurodevelopmental outcomes is sparse but the present literature is suggestive of
      a negative impact in cases of surgically managed NEC.

PMID- 27032754
TI  - Polymyositis in a patient with ulcerative colitis.

PMID- 27032755
TI  - Value of body mass index in the diagnosis of obesity according to DEXA in well
      controlled RA patients.
AB  - BACKGROUND: Rheumatoid arthritis (RA) has an indirect effect on body composition.
      Body mass index (BMI) is not a valid predictor of body fat in RA patients.
      OBJECTIVE: To evaluate the accuracy of BMI in identifying obesity diagnosed
      according to dual energy X-ray absorptiometry (DXA) in well-controlled RA
      patients. METHODS: An observational, cross-sectional, descriptive, analytical
      study. We used 3 different cutoffs for obesity as determined by DXA: >35% total
      fat, >40% total fat, and >35% central fat mass (central obesity). RESULTS: One
      hundred one patients were included. We found that 35% total fat corresponded to a
      BMI of 24kg/m2, with a sensitivity of 90% and specificity of 75% (area under the
      curve [AUC] 0.917); 40% total fat to a BMI of 25kg/m2, with a sensitivity of 86%
      and specificity of 39% (AUC 0.822); and 35% central fat mass to a BMI of 22kg/m2,
      with a sensitivity of 97% and specificity of 84% (AUC 0.951). CONCLUSION: Obesity
      according to DXA was underdiagnosed when the classic BMI cutoffs were used in
      well-controlled RA patients.

PMID- 27032756
TI  - Participation of prostaglandin D2 in the mobilization of the nuclear-localized
      CTP:phosphocholine cytidylyltransferase alpha in renal epithelial cells.
AB  - Phosphatidylcholine (PC) is the main constituent of mammalian cell membranes.
      Consequently, preservation of membrane PC content and composition - PC
      homeostasis - is crucial to maintain cellular life. PC biosynthetic pathway is
      generally controlled by CTP:phosphocholine cytidylyltransferase (CCT), which is
      considered the rate-limiting enzyme. CCTalpha is an amphitropic protein, whose
      enzymatic activity is commonly associated with endoplasmic reticulum
      redistribution. However, most of the enzyme is located inside the nuclei. Here,
      we demonstrate that CCTalpha is the most abundant isoform in renal collecting
      duct cells, and its redistribution is dependent on endogenous prostaglandins.
      Previously we have demonstrated that PC synthesis was inhibited by indomethacin
      (Indo) treatment, and this effect was reverted by exogenous PGD(2). In this work
      we found that Indo induced CCTalpha distribution into intranuclear Lamin A/C
      foci. Exogenous PGD(2) reverted this effect by inducing CCTalpha redistribution
      to nuclear envelope, suggesting that PGD(2) maintains PC synthesis by CCTalpha
      mobilization. Interestingly, we found that the effect of PGD(2) was dependent on
      ERK1/2 activation. In conclusion, our previous observations and the present
      results lead us to suggest that papillary cells possess the ability to maintain
      their structural integrity through the synthesis of their own survival molecule,
      PGD(2), by modulating CCTalpha intracellular location.

PMID- 27032757
TI  - [Quality is not a problem: It is a solution].

PMID- 27032758
TI  - [Second General Assembly of the WATOG (World Association of Trainees in
      Obstetrics and Gynecology) at the XXI FIGO World Congress in Vancouver (Canada)
      from October 5 to 9, 2015].

PMID- 27032759
TI  - [Trisomy 21 and breast cancer: A genetic abnormality which protects against
      breast cancer?].
AB  - INTRODUCTION: Trisomy 21 (T21) is the most common chromosomal abnormality and one
      of the main causes of intellectual disability. The tumor profile of T21 patients
      is characterized by the low frequency of solid tumors including breast cancer.
      METHODS: The objective of this work was to analyze the literature to find
      possible clues for the low frequency of breast cancer in T21 persons with a focus
      on one hand to the various risks and protective factors against breast cancer for
      women T21, and on the other hand to changes in the expression of different genes
      located on chromosome 21. RESULTS: T21 women have hormonal and societal risk
      factors for breast cancer: frequent nulliparity, lack of breastfeeding, physical
      inactivity and high body mass index. The age of menopause, earlier in T21 women,
      has a modest protective effect against breast cancer. The low rate of breast
      tumors in T21 women is probably mainly linked to the reduced life expectancy
      compared to the general population (risk of death before the age of onset of the
      majority of breast cancers) and the presence of a third chromosome 21,
      characterizing the disease. It might lead to the increased expression of a number
      of genes contributing directly or undirectly to tumor suppression, decreased
      tumor angiogenesis and increased cell apoptosis. Moreover, changes in the mammary
      stroma of persons T21 could have an inhibitory role on the development of breast
      tumors. CONCLUSION: The low frequency of breast cancers for T21 patients may not
      only be explained by hormonal and societal factors, but also by genetic
      mechanisms which could constitute an interesting axis of research in breast
      cancer.

PMID- 27032760
TI  - [Partial cystectomy for bladder endometriosis: Robotic assisted laparoscopy
      versus standard laparoscopy].
AB  - OBJECTIVES: To compare robot-assisted laparoscopy (RL) and conventional
      laparoscopy (CL) in surgery for bladder endometriosis. METHODS: A retrospective
      study was conducted between January 2007 and December 2013, including patients
      with bladder endometriosis receiving at least a partial cystectomy by RL or CL.
      The primary endpoint was the presence of a radiological recurrence at bladder
      level. RESULTS: We included 15 patients in the RL group and 22 in the CL group.
      The median age was 29 years+/-7 years. The symptoms were similar in the 2 groups.
      Pre-surgical mapping of the lesions was carried out with MRI. Sixty percent of
      patients in the RL group vs 91% in the CL group had other associated
      endometriosis lesions, P=0.04. The median size of the bladder lesion was 30+/-8mm
      in the RL group vs 23+/-7mm in the CL group, P=0.03. The median operative time
      was 210 vs 225min, P=0.8. We did not find any significant difference in
      intraoperative and early and late postoperative complications between the 2
      groups. The median length of stay was 5 days vs 6 days. The proportion of relapse
      was 20 vs 23%, P>0.05. Clinical improvement was similar between the groups, i.e.
      93 vs 86%, P=0.6 and the pregnancy rate was 93 vs 86%, P=0.6. CONCLUSIONS: Robot
      assisted laparoscopy in the surgical treatment of bladder endometriosis as
      compared to traditional laparoscopy does not seem to have an adverse effect
      neither on the risk of recurrence nor on the occurrence of intra- and
      postoperative complications.

PMID- 27032761
TI  - [Prenatal and clinicopathological study of 6 cases of Pallister-Killian syndrome
      and review].
AB  - OBJECTIVE: In multidisciplinary prenatal diagnosis centers, the search for a
      tetrasomy 12p mosaic is requested following the discovery of a diaphragmatic
      hernia in the antenatal period. Thus, the series of Pallister Killian syndromes
      (PKS: OMIM 601803) probably overestimate the prevalence of diaphragmatic hernia
      in this syndrome to the detriment of other morphological abnormalities. METHODS:
      A multicenter retrospective study was conducted with search for assistance from
      members of the French society for Fetal Pathology. For each identified case, we
      collected all antenatal and postnatal data. Antenatal data were compared with
      data from the clinicopathological examination to assess the adequacy of
      sonographic signs of PKS. A review of the literature on antenatal morphological
      anomalies in case of PKS completed the study. RESULTS: Ten cases were referred to
      us: 7 had cytogenetic confirmation and 6 had ultrasound screening. In the
      prenatal as well as post mortem period, the most common sign is facial
      dysmorphism (5 cases/6). A malformation of limbs is reported in half of the cases
      (3 out of 6). Ultrasound examination detected craniofacial dysmorphism in 5 cases
      out of 6. We found 1 case of left diaphragmatic hernia. Our results are in
      agreement with the malformation spectrum described in the literature. CONCLUSION:
      Some malformation associations could evoke a SPK without classical diaphragmatic
      hernia.

PMID- 27032763
TI  - Corrigendum.

PMID- 27032762
TI  - [How I perform... a uterine morcellation in an isolation bag?].

PMID- 27032764
TI  - Impact on CYP19A1 activity by mutations in NADPH cytochrome P450 oxidoreductase.
AB  - Cytochrome P450 aromatase (CYP19A1), in human placenta metabolizes androgens to
      estrogens and uses reduced nicotinamide adenine dinucleotide phosphate through
      cytochrome P450 oxidoreductase (POR) for the energy requirements of its metabolic
      activities. Mutations in the human POR lead to congenital adrenal hyperplasia due
      to loss of activities of several steroid metabolizing enzymatic reactions
      conducted by the cytochrome P450 proteins located in the endoplasmic reticulum.
      Effect of POR mutations on different P450 activities depend on individual partner
      proteins. In this report we have studied the impact of mutations found in the POR
      on the enzymatic activity of CYP19A1. We expressed wild type as well mutant human
      POR proteins in bacteria and purified the recombinant proteins, which were then
      used in an in vitro reconstitution system in combination with CYP19A1 and lipids
      for enzymatic analysis. We found that several mutations as well as polymorphisms
      in human POR can cause reduction of CYP19A1 activity. This would affect
      metabolism of estrogens in people with variations of POR allele. The POR mutants
      Y181D and R616X were found to have no activity in supporting CYP19A1 reactions.
      The POR mutations Y607C and delF646 showed a loss of 60-90% activity and two
      polymorphic forms of POR, R316W and G413S showed similar to WT activity. One POR
      variant, Q153R had almost double the activity of WT. Loss of CYP19A1 activity may
      contribute to disordered steroidogenesis in female patients with POR mutations as
      well as in mothers with POR variants carrying a male child.

PMID- 27032765
TI  - Corrigendum.
AB  - Loh B, Chen JY, Yew AKS, et al. Prevalence of metatarsus adductus in symptomatic
      hallux valgus and its influence on functional outcome.Foot Ankle
      Int.2015;36(11):1316-1321. (Original DOI:10.1177/1071100715595618). 

PMID- 27032767
TI  - Effect of pH on the structure, function, and stability of human
      calcium/calmodulin-dependent protein kinase IV: combined spectroscopic and MD
      simulation studies.
AB  - Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of
      Ser/Thr protein kinase family. It is regulated by the calcium-calmodulin
      dependent signal through a secondary messenger, Ca(2+), which leads to the
      activation of its autoinhibited form. The over-expression and mutation in CAMKIV
      as well as change in Ca(2+) concentration is often associated with numerous
      neurodegenerative diseases and cancers. We have successfully cloned, expressed,
      and purified a functionally active kinase domain of human CAMKIV. To observe the
      effect of different pH conditions on the structural and functional properties of
      CAMKIV, we have used spectroscopic techniques such as circular diachroism (CD)
      absorbance and fluorescence. We have observed that within the pH range 5.0-11.5,
      CAMKIV maintained both its secondary and tertiary structures, along with its
      function, whereas significant aggregation was observed at acidic pH (2.0-4.5). We
      have also performed ATPase activity assays under different pH conditions and
      found a significant correlation between the structure and enzymatic activities of
      CAMKIV. In-silico validations were further carried out by modeling the 3
      dimensional structure of CAMKIV and then subjecting it to molecular dynamics (MD)
      simulations to understand its conformational behavior in explicit water
      conditions. A strong correlation between spectroscopic observations and the
      output of molecular dynamics simulation was observed for CAMKIV.

PMID- 27032768
TI  - Turn down genes for WAT? Activation of anti-apoptosis pathways protects white
      adipose tissue in metabolically depressed thirteen-lined ground squirrels.
AB  - During hibernation, the metabolic rate of thirteen-lined ground squirrels
      (Ictidomys tridecemlineatus) can drop to <5 % of normal resting rate at 37 
      degrees C, core body temperature can decrease to as low as 1-5  degrees C, and
      heart rate can fall from 350-400 to 5-10 bpm. Energy saved by hibernating allows
      squirrels to survive the winter when food is scarce, and living off lipid
      reserves in white adipose tissue (WAT) is crucial. While hibernating, some energy
      must be used to cope with conditions that would normally be damaging for mammals
      (e.g., low core body temperatures, ischemia) and could induce cell death via
      apoptosis. Cell survival is largely dependent on the relative amounts and
      activities of pro- and anti-apoptotic Bcl-2 family proteins. The present study
      analyzed how anti-apoptotic proteins respond to protect WAT cells during
      hibernation. Relative levels of several anti-apoptotic proteins were quantified
      in WAT via immunoblotting over six time points of the torpor-arousal cycle. These
      included anti-apoptotic Bcl-2 family members Bcl-2, Bcl-xL, and Mcl-l, as well as
      caspase inhibitors x-IAP and c-IAP. Changes in the relative protein levels and/or
      phosphorylation levels were also observed for various regulators of apoptosis (p
      JAKs, p-STATs, SOCS, and PIAS). Mcl-1 and x-IAP protein levels increased whereas
      Bcl-xL, Bcl-2, and c-IAP protein/phosphorylation levels decreased signifying
      important roles for certain Bcl-2 family members in cell survival over the torpor
      arousal cycle. Importantly, the relative phosphorylation of selected STAT
      proteins increased, suggesting a mechanism for Bcl-2 family activation. These
      results suggest that an increase in WAT cytoprotective mechanisms supports
      survival efforts during hibernation. 

PMID- 27032769
TI  - Novel anti-cancer agent myrtucommulone-A and thymoquinone abrogate epithelial
      mesenchymal transition in cancer cells mainly through the inhibition of PI3K/AKT
      signalling axis.
AB  - Epithelial-mesenchymal transition (EMT) plays a prominent role in cancer
      progression and metastasis. Inhibition of EMT-associated regulators may hold a
      huge promise for cancer therapy. Although TGF-beta signalling has a pivotal role
      in the induction of EMT, alterations during the EMT process are usually initiated
      and controlled by the cross-talk of multiple signalling pathways, and in most
      cases this is context-dependent. In the present study, we aimed at identifying
      the molecular mechanisms during the inhibition of EMT by novel anti-cancer agent
      myrtucommulone-A (MC-A) and thymoquinone (TQ). We used epithelial cancer cells to
      study the effects of MC-A and TQ on EMT. We first showed the functional
      inhibition of EMT by MC-A or TQ using migration assays and confirmed the EMT
      inhibition by analysing the expression of EMT markers with RT-PCR,
      immunocytochemistry and Western blotting. We evaluated the changes in
      intracellular dynamics by Western blotting and compared the effects of MC-A and
      TQ with the effects of selective inhibitors of PI3K (LY294002), ERK 1/2 (U0126)
      and TGF-betaR (SB431542). We demonstrate that both MC-A and TQ treatment
      negatively regulate the EMT process through modulation of signalling pathways in
      cancer cells. MC-A and TQ treatment inhibited phosphorylation of multiple
      proteins in a context-dependent manner. Novel anti-cancer agent MC-A and TQ
      regulate distinct signalling pathways for the repression of EMT which emphasises
      the significance of combinational therapies in cancer treatment. MC-A and TQ
      could be considered as candidate molecules for combinational therapies with their
      ability to interfere signalling pathways regulating cancer cell behaviour. 

PMID- 27032770
TI  - Central Venous Access in the Pediatric Population With Emphasis on Complications
      and Prevention Strategies.
AB  - Central venous catheters are often necessary in the pediatric population. Access
      may be challenging, and each vessel presents its own unique set of risks and
      complications. Central venous catheterization is useful for hemodynamic
      monitoring, rapid fluid infusion, and administration of hyperosmolar medications,
      including vasopressors, antibiotics, chemotherapy, and parenteral nutrition.
      Recent advances have improved the catheters used as well as techniques for
      insertion. A serious complication of central access is infection, which is
      associated with morbidity, mortality, and significant financial costs. Reduction
      of catheter-related bloodstream infections is realized with use of ethanol locks,
      single lumens when appropriate, and prudent adherence to insertion and
      maintenance bundles. Ultrasound guidance used for central venous catheter
      placement improves accuracy of placement, reducing time and unsuccessful
      insertion and complication rates. Patients with central venous catheters are best
      served by multidisciplinary team involvement. 

PMID- 27032772
TI  - Erratum to: Reliability and validity of Japanese versions of KIDSCREEN-27 and
      KIDSCREEN-10 questionnaires.

PMID- 27032771
TI  - HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a
      Mitochondrial Pathway.
AB  - Addictive stimulant drugs, such as cocaine, are known to increase the risk of
      exposure to HIV-1 infection and hence predispose towards the development of AIDS.
      Previous findings suggested that the combined effect of chronic cocaine
      administration and HIV-1 infection enhances cell death. Neuronal survival is
      highly dependent on the health of mitochondria providing a rationale for
      assessing mitochondrial integrity and functionality following cocaine treatment,
      either alone or in combination with the HIV-1 viral protein Tat, by monitoring
      ATP release and mitochondrial membrane potential (DeltaPsim). Our results
      indicate that exposing human and rat primary hippocampal neurons to cocaine and
      HIV-1 Tat synergistically decreased both mitochondrial membrane potential and ATP
      production. Additionally, since previous studies suggested HIV-1 infection alters
      autophagy in the CNS, we investigated how HIV-1 Tat and cocaine affect autophagy
      in neurons. The results indicated that Tat induces an increase in LC3-II levels
      and the formation of Parkin-ring-like structures surrounding damaged
      mitochondria, indicating the possible involvement of the Parkin/PINK1/DJ-1 (PPD)
      complex in neuronal degeneration. The importance of mitochondrial damage is also
      indicated by reductions in mitochondrial membrane potential and ATP content
      induced by HIV-1 Tat and cocaine.

PMID- 27032773
TI  - Quantitative effects of a declaration of a state of emergency on foot-and-mouth
      disease.
AB  - OBJECTIVES: The law in Japan requires the declaration of a state of emergency and
      implementation of countermeasures for an epidemic of a new infectious disease.
      However, because a state of emergency has never been declared in Japan, its
      effects remain unknown. The required countermeasures are similar to those
      implemented in the foot-and-mouth disease epidemic in Miyazaki in 2010. This
      study aimed to quantitatively estimate the effect of the declaration in 2010 and
      investigate the nature of the epidemic based on the day on which the declaration
      took effect. METHODS: Only publicly available data were used. Data for farms in
      the most affected town were analyzed. A modified susceptible-infected-recovered
      model was used to estimate the effect and for the simulation. Another model was
      used to estimate the effective reproduction number. RESULTS: After the
      declaration, the intra-bovine transmission rate decreased by 18.1 %, and there
      were few days when the effective reproduction number was >1.0. A few weeks delay
      in the declaration significantly increased the possibility of epidemic, number of
      farms at peak, and final infection scale. CONCLUSIONS: Based on the substantial
      decrease in the transmission rate after the declaration of a state of emergency
      in 2010, a future declaration will have a similar effect for a new infectious
      disease even though a direct extrapolation is not valid. Although a declaration
      should be carefully considered owing to the potential socioeconomic effects, it
      is essential to prepare for the implementation given that a delay of only a few
      weeks should be acceptable.

PMID- 27032774
TI  - Long-term treatment of chronic migraine with OnabotulinumtoxinA: efficacy,
      quality of life and tolerability in a real-life setting.
AB  - Botulinum toxin was shown to be effective in treatment of chronic migraine. We
      wanted to explore its efficacy and tolerability in chronic application under real
      life conditions. For this, 27 consecutive patients (age 45.6 +/- 10.8 years, 25
      females, 2 males) received altogether 176 injection series (IS) with 189.7 +/-
      45.8MU onabotulinumtoxinA (Botox((r))) according to the PREEMPT scheme. During
      the study period altogether 6.5 +/- 2.9 (min 4, max 13) IS were applied per
      patient (total treatment time of 73.1 +/- 36.9 weeks). 96 % of the patients
      reported benefit. Monthly headache days were reduced from 18.9 +/- 3.9 to 8.7 +/-
      4.5 (p < 0.001, -53.7 %), migraine days from 16.8 +/- 4.9 to 7.4 +/- 4.6 (p <
      0.001, -55.1 %), autonomic days from 8.6 +/- 7.5 to 2.7 +/- 4.2 (p < 0.001, -71.9
      %) and medication days from 14.2 +/- 4.6 to 8.3 +/- 4.2 (p < 0.001, -71.1 %).
      Health-related quality of life improved by 0.6-1.5 standard deviations (SD)
      (Short Form Health Survey), migraine-related quality of life by 1.4-2.0 SD
      (Migraine-Specific Quality of Life Questionnaire) and by 1.9 SD (Headache Impact
      Test), depression by 1.1 SD (Beck Depression Inventory). Subjective global
      clinical improvement was 2.6 +/- 0.6 (Global Clinical Improvement Scale). All
      improvements were stable throughout the entire study period. Adverse effects were
      infrequent, mild and transient. Botulinum toxin provides highly effective and
      safe long-term treatment of chronic migraine.

PMID- 27032775
TI  - Secondary task performance during challenging walking tasks and freezing episodes
      in Parkinson's disease.
AB  - Parkinson's disease (PD) patients likely use attentional strategies to compensate
      for their gait deficits, which increases the cognitive challenge of walking. The
      interplay between cognitive functions and gait can be investigated by evaluating
      the subject's attendance to a secondary task during walking. We hypothesized that
      the ability to attend to a secondary task decreases during challenging walking
      conditions in PD, particularly during freezing of gait (FOG)-episodes. Twenty
      nine PD patients and 14 age-matched controls performed a simple reaction task
      that involved squeezing a ball as fast as possible in response to an auditory
      stimulus. Participants performed this reaction task during four conditions: (1)
      walking at preferred speed; (2) walking with short steps at preferred speed; (3)
      walking with short steps, as rapidly as possible; (4) making rapid full turns. We
      used surface electromyography to determine reaction times, and a pressure sensor
      located within the ball to determine movement onset. Reaction times of PD
      patients were slower (on average by 42 ms) compared to controls, regardless of
      the walking task. In both groups, reaction times were significantly longer during
      the turning condition compared to all other conditions. FOG-episodes were most
      often seen during the turning condition. In PD patients, reaction times were
      significantly longer during FOG-episodes compared to trials without FOG. Our
      results suggest that turning requires more attentional resources than other
      walking tasks. The observation of delayed reaction times during FOG-episodes
      compared to trials without FOG suggests that freezers use additional resources to
      overcome their FOG-episodes.

PMID- 27032777
TI  - ASSESSMENT OF AGE-DEPENDENT RADIATION DOSE DUE TO INTAKE OF URANIUM AND THORIUM
      IN DRINKING WATER FROM SIKAR DISTRICT, RAJASTHAN, INDIA.
AB  - The concentrations of 238U and 232Th have been determined in drinking water
      samples collected from the Sikar district of Rajasthan State, India. The samples
      have been analysed by using high-resolution inductively coupled plasma mass
      spectrometry. 238U content in water samples ranged from 8.20 to 202.63 ug l-1 and
      232Th content ranged from 0.57 to 1.46 ug l-1 The measured 238U content in 25 %
      of the analysed samples exceeded the World Health Organization (WHO) and United
      States Environmental Protection Agency drinking water guidelines of 30 ug l-1 and
      12.5 % of the samples exceeded the 60 ug l-1 Indian maximum acceptable
      concentration recommended by the Atomic Energy Regulatory Board, India. The
      annual effective doses (uSv y-1) due to ingestion of 238U and 232Th for different
      age groups were also calculated. The results compared with the recommended value
      reported by the WHO.

PMID- 27032776
TI  - Protein aggregation as a mechanism of adaptive cellular responses.
AB  - Coalescence of proteins into different types of intracellular bodies has surfaced
      as a widespread adaptive mechanism to re-organize cells and cellular functions in
      response to specific cues. These structures, composed of proteins or protein-mRNA
      complexes, regulate cellular processes through modulating enzymatic activities,
      gene expression or shielding macromolecules from damage. Accordingly, such bodies
      are associated with a wide-range of processes, including meiosis, memory
      encoding, host-pathogen interactions, cancer, stress responses, as well as
      protein quality control, DNA replication stress and aneuploidy. Importantly,
      these distinct coalescence responses are controlled, and in many cases regulated
      by chaperone proteins. While cells can tolerate and proficiently coordinate
      numerous distinct types of protein bodies, some of them are also intimately
      linked to diseases or the adverse effects of aging. Several protein bodies that
      differ in composition, packing, dynamics, size, and localization were originally
      discovered in budding yeast. Here, we provide a concise and comparative review of
      their nature and nomenclature.

PMID- 27032778
TI  - RADIUM AND RADON EXHALATION RATE IN SOIL SAMPLES OF HASSAN DISTRICT OF SOUTH
      KARNATAKA, INDIA.
AB  - The radon exhalation rate was measured in 32 soil samples collected from Hassan
      district of South Karnataka. Radon exhalation rate of soil samples was measured
      using can technique. The results show variation of radon exhalation rate with
      radium content of the soil samples. A strong correlation was observed between
      effective radium content and radon exhalation rate. In the present work, an
      attempt was made to assess the levels of radon in the environment of Hassan.
      Radon activities were found to vary from 2.25+/-0.55 to 270.85+/-19.16 Bq m-3 and
      effective radium contents vary from 12.06+/-2.98 to 1449.56+/-102.58 mBq kg-1
      Surface exhalation rates of radon vary from 1.55+/-0.47 to 186.43+/-18.57 mBq m-2
      h-1, and mass exhalation rates of radon vary from 0.312+/-0.07 to 37.46+/-2.65
      mBq kg-1 h-1.

PMID- 27032779
TI  - A COMPARATIVE STUDY OF DIURNAL VARIATION OF RADON AND THORON CONCENTRATIONS IN
      INDOOR ENVIRONMENT.
AB  - The diurnal measurements of radon and thoron concentrations were performed in the
      indoor environment of Nuclear Research Laboratory, Badshahi Thaul, Tehri Garhwal,
      Uttarakhand, India by using AlphaGUARD, Portable Radon Monitor (SMART RnDuo) and
      RAD7. Using AlphaGUARD, the radon concentration was found to vary from 8 to 94 Bq
      m-3 with an average of 41.5+/-22.2 Bq m-3 Using Portable Radon Monitor (SMART
      RnDuo), the concentration was found to vary from 2 to 101 Bq m-3 with an average
      of 41.7+/-23.6 Bq m-3, and with RAD7, the concentration was found to vary from 3
      to 99 Bq m-3 with an average of 40+/-20.3 Bqm-3 While the thoron concentration
      using Portable Radon Monitor (SMART RnDuo) was found to vary from 4 to 65 Bq m-3
      with an average of 17.3+/-12.9 Bqm-3, and using RAD7, the concentration was found
      to vary from 5 to 90 Bq m-3 with an average of 29.8+/-17.3 Bq m-3.

PMID- 27032780
TI  - EMISSION OF SOIL GAS RADON CONCENTRATION AROUND MAIN CENTRAL THRUST IN UKHIMATH
      (RUDRAPRAYAG) REGION OF GARHWAL HIMALAYA.
AB  - In this paper, the result of systematic measurement of the soil gas radon
      concentrations is discussed and the background values are defined along and
      around the Main Central Thrust (MCT) in Ukhimath region of Garhwal Himalaya,
      India. The Ukhimath region is being subjected to intense neotectonic activities
      like earthquake and landslide. For the systematic study, the measurement has been
      done in grid pattern form along and across the MCT. The soil gas radon
      concentrations were measured using RAD7 with appropriate accessories and followed
      proper protocol proposed by the manufacturer. The soil gas concentration was
      measured at different depths 10, 30 and 50 cm with a wide range of different
      points from the MCT. At 10 cm depth, the soil gas radon concentration was found
      to vary from 125 to 800 Bq m-3 with an average of 433 Bq m-3; at 30 cm, it was
      found to vary from 203 to 32 500 Bq m-3 with an average of 2387 Bq m-3; and at 50
      cm, it was found to vary from 1330 to 46 000 Bq m-3 with an average of 15 357 Bq
      m-3 The data analysis clearly reveals anomalous values along the fault.

PMID- 27032781
TI  - MEASUREMENT OF RADON CONCENTRATION IN DWELLINGS IN THE REGION OF HIGHEST LUNG
      CANCER INCIDENCE IN INDIA.
AB  - Indoor radon/thoron concentration has been measured in Aizawl district, Mizoram,
      India, which has the highest lung cancer incidence rates among males and females
      in India. Simultaneously, radon flux emanated from the surrounding soil of the
      dwellings was observed in selected places. The annual average value of
      concentration of radon(thoron) of Aizawl district is 48.8(22.65) Bq m-3 with a
      geometric standard deviation of 1.25(1.58). Measured radon flux from the soil has
      an average value of 22.6 mBq m-2 s-1 These results were found to be much below
      the harmful effect or action level as indicated by the World Health Organisation.
      On the other hand, food habit and high-level consumption of tobacco and its
      products in the district have been found to increase the risk of lung cancer
      incidence in the district.

PMID- 27032782
TI  - RADIATION DOSE DUE TO RADON AND HEAVY METAL ANALYSIS IN DRINKING WATER SAMPLES OF
      JAMMU DISTRICT, JAMMU & KASHMIR, INDIA.
AB  - In the present investigation, radon concentration and heavy metal analysis were
      carried out in drinking water samples in Jammu district, Jammu & Kashmir, India.
      The radon concentration was measured by using RAD-7, portable alpha particle
      detector. The values of radon concentration in drinking water samples were also
      compared within the safe limit recommended by different health agencies. The
      total annual effective dose ranged from 53.04 to 197.29 uSv y-1 The annual
      effective dose from few locations from the studied area was found to be greater
      than the safe limit (100 uSv y-1) suggested by World Health Organisation (WHO)
      and EU Council. Heavy metal concentration was determined by atomic absorption
      spectrophotometer. A total of eight elements were analysed, viz. arsenic,
      mercury, zinc, iron, copper, chromium, manganese and cadmium. Heavy metals are
      considered to be the major pollutants of water sources. The results were compared
      with the limits of WHO, EU and Indian organisations. The trace metal analysis is
      not on the exceeding side of the permissible limit in all the samples.

PMID- 27032783
TI  - DISTRIBUTION OF 210PO IN HEMAVATHI RIVERINE ENVIRONMENT.
AB  - In the present investigation, the concentration of 210Po was measured in soil and
      sediment samples from riverine environment of Hemavathi river of south Karnataka.
      The 210Po in the samples was separated by radiochemical method, and the activity
      was counted using ZnS(Ag) alpha counter. Seasonal variation of 210Po was studied
      for soil and sediment samples. The mean activity of 210Po in monsoon was higher
      than that in pre-monsoon samples. The granulometric contents (sand, silt and
      clay), organic matter and pH contents were measured in soil, and sediment,
      respectively. The organic matter content and clay positively correlated with
      210Po activity. There is a good correlation between activity concentration of
      210Po and organic matter in both monsoon and pre-monsoon samples. Using the SPSS
      22 statistical software, the median, skewness, kurtosis, variance and frequency
      distribution were calculated.

PMID- 27032784
TI  - Childhood Emotional Maltreatment as a Robust Predictor of Suicidal Ideation: A 3
      Year Multi-Wave, Prospective Investigation.
AB  - Despite literature suggesting a relationship between child maltreatment and
      suicidal ideation, few studies have examined the prospective course of this
      relationship. The current study examined this relationship in a sample of 682
      community youth who were followed over the course of 3 years. Repeated measures
      of suicidal ideation, emotional maltreatment, and depressive symptom severity
      were examined in multi-wave path analysis models. Overall, results suggest that
      emotional maltreatment over time contributes uniquely to the prospective
      prediction of suicidal ideation, even when controlling for age, previous suicidal
      ideation, biological sex, and depression symptom severity. Unlike previous
      studies that have only measured emotional maltreatment at one-time point, the
      current study demonstrates that emotional maltreatment contributes unique risk to
      suicidal ideation prospectively among youth. Results speak to the importance of
      examining emotional maltreatment and suicidal ideation within prospective models
      of risk and suggest that emotional maltreatment is a robust predictor of suicidal
      ideation, over and above history of suicidal ideation and depression.

PMID- 27032786
TI  - Is There a Role for Diet in the Therapy of Rheumatoid Arthritis?
AB  - Patients with rheumatoid arthritis (RA) often inquire about dietary interventions
      to improve RA symptoms. Although the majority of studies of diet and RA were
      published prior to the start of the twenty-first century, this review discusses
      the evidence for a relationship between diet, in particular omega-3 fatty acid
      supplements, vitamin D supplements, alcohol, and the Mediterranean diet and RA
      disease activity. We review possible mechanisms by which these dietary intakes
      may affect RA disease activity. Given the complexity of studying the relationship
      between diet and RA disease activity, we highlight areas deserving further study
      before specific recommendations can be made to RA patients.

PMID- 27032785
TI  - Wheat miRNA ancestors: evident by transcriptome analysis of A, B, and D genome
      donors.
AB  - MicroRNAs are critical players of post-transcriptional gene regulation with
      profound effects on the fundamental processes of cellular life. Their
      identification and characterization, together with their targets, hold great
      significance in exploring and exploiting their roles on a functional context,
      providing valuable clues into the regulation of important biological processes,
      such as stress tolerance or environmental adaptation. Wheat is a hardy crop,
      extensively harvested in temperate regions, and is a major component of the human
      diet. With the advent of the next generation sequencing technologies considerably
      decreasing sequencing costs per base-pair, genomic, and transcriptomic data from
      several wheat species, including the progenitors and wild relatives have become
      available. In this study, we performed in silico identification and comparative
      analysis of microRNA repertoires of bread wheat (Triticum aestivum L.) and its
      diploid progenitors and relatives, Aegilops sharonensis, Aegilops speltoides,
      Aegilops tauschii, Triticum monococcum, and Triticum urartu through the
      utilization of publicly available transcriptomic data. Over 200 miRNA families
      were identified, majority of which have not previously been reported. Ancestral
      relationships expanded our understanding of wheat miRNA evolution, while T.
      monococcum miRNAs delivered important clues on the effects of domestication on
      miRNA expression. Comparative analyses on wild Ae. sharonensis accessions
      highlighted candidate miRNAs that can be linked to stress tolerance. The miRNA
      repertoires of bread wheat and its diploid progenitors and relatives provide
      important insight into the diversification and distribution of miRNA genes, which
      should contribute to the elucidation of miRNA evolution of Poaceae family. A
      thorough understanding of the convergent and divergent expression profiles of
      miRNAs in different genetic backgrounds can provide unique opportunities to
      modulation of gene regulation for better crop performance.

PMID- 27032788
TI  - The Role of ANK in Calcium Pyrophosphate Deposition Disease.
AB  - The protein product of the progressive ankylosis gene, known as ANK, is a 492
      amino acid multi-pass transmembrane protein. This protein is critical for the
      regulation of pyrophosphate, and gain of function ANK mutations is associated
      with calcium pyrophosphate deposition disease. Much about the structure,
      function, and regulation of ANK remain unstudied. This review of the current
      literature examines recent contributions to our understanding of ANK. We focus on
      new work on the function, binding partners, and regulators of ANK. A more
      complete understanding of this important protein may help to identify future
      therapeutic targets for the treatment of calcium pyrophosphate deposition
      disease.

PMID- 27032787
TI  - Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence.
AB  - Cognitive difficulties represent a common and debilitating feature of the
      enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self
      reported problems with attention, memory, and concentration and present
      objectively as slowed information processing speed particularly on complex tasks
      requiring sustained attention. The mechanisms underlying cognitive dysfunction
      remain to be established; however, alterations in autonomic nervous system
      activity and cerebral blood flow have been proposed as possibilities.
      Heterogeneity in the experience of cognitive impairment, as well as differences
      in the methods utilised to quantify dysfunction, may contribute to the
      difficulties in establishing plausible biological underpinnings. The development
      of a brief neurocognitive battery specifically tailored to CFS and adoption by
      the international research community would be beneficial in establishing a
      profile of cognitive dysfunction. This could also provide better insights into
      the underlying biological mechanisms of cognitive dysfunction in CFS and enhance
      the development of targeted treatments.

PMID- 27032789
TI  - Prevention of Recurrent Thrombosis in Antiphospholipid Syndrome: Different from
      the General Population?
AB  - Antiphospholipid syndrome (APS) is characterized by arterial and/or venous
      thrombosis with or without pregnancy morbidity in the presence of autoantibodies
      targeting proteins that associate with membrane phospholipids, termed
      "antiphospholipid antibodies" (aPL). Management of arterial and venous thromboses
      shares some similarities with management of arterial and venous thromboses in the
      general population; however, there are key differences. The majority of studies
      addressing management of thrombotic APS focus on secondary prevention. Vitamin K
      antagonists (VKA) are typically used for secondary prevention of venous
      thromboembolism in APS. Optimal management of isolated arterial thrombosis, in
      particular ischemic stroke, in patients with APS is controversial, and proposed
      therapeutic options have included antiplatelet agents and VKA. Primary
      prophylaxis in aPL-positive patients should be an individualized decision taking
      into account patient-specific risks. There may be a role for adjuvant therapies
      such as hydroxychloroquine, vitamin D, statins, or novel therapeutics in specific
      patient populations.

PMID- 27032791
TI  - Pediatric Mixed Connective Tissue Disease.
AB  - Pediatric-onset mixed connective tissue disease is among the rare disease
      entities in pediatric rheumatology and includes features of arthritis,
      polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic
      sclerosis. Accurate recognition and diagnosis of the disease is paramount to
      prevent long-term morbidity. Advances in the genetic and immunologic
      understanding of the factors involved in the etiopathogenesis provide an
      opportunity for improvements in prognostication and targeted therapy. The
      development of a multinational cohort of patients with mixed connective tissue
      disease would be invaluable to provide more updated data regarding the clinical
      presentation, to develop a standardized treatment approach, disease activity and
      outcome tools, and to provide data on long-term outcomes and comorbidities.

PMID- 27032792
TI  - Fungal Infections and New Biologic Therapies.
AB  - The development of biologic therapies targeting proinflammatory mediators has led
      to significant advances in the treatment of immune-mediated inflammatory diseases
      (IMIDs). Blocking undesired inflammatory effects also has the potential to
      disrupt the body's immune response and increase the risk for infections,
      including fungal infections. This review summarizes the published data on the
      frequency and risk for fungal infections among patients treated with biologics,
      with a focus on the newer therapies approved for use with IMIDs in the last 10
      years. The use of biologics is associated with a small but important risk of
      fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and
      candidiasis are some of the most common fungal infections associated with
      biologics. Providers should be vigilant for fungal infection among patients
      taking biologics, be aware that biologic agents may alter the typical
      presentation of fungal infections, and take timely steps to diagnose and treat
      fungal infection to reduce resultant morbidity and mortality.

PMID- 27032790
TI  - Rheumatoid Arthritis Pharmacotherapies: Do They Have Anti-Atherosclerotic
      Activity?
AB  - Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular
      disease (CVD) events, presumably related to a greater burden of atherosclerosis,
      as well as atherosclerotic plaques that tend to be inflamed and rupture prone.
      Many of the inflammatory pathways underlying the pathobiology of RA are also
      recognized contributors to atherosclerosis. Immunomodulation is the mainstay for
      RA therapy, and a variety of biologic and non-biologic pharmacotherapies are used
      either singly or in combination to control articular and systemic inflammation
      and prevent joint destruction. Almost all of these agents have theoretical
      potential to favorably affect atherogenesis and atherothrombosis, but mechanisms
      by which they exert effects have been incompletely studied, to date. However,
      whether clinical control of RA disease activity is associated with a reduction in
      CVD events regardless of agent used or whether the potency of anti-atherogenic
      effects varies between disease-modifying anti-rheumatic drugs (DMARDs) is an area
      of current interest in RA research. More broadly, RA immunotherapies are
      currently being tested in high-CVD-risk patients in proof-of-concept clinical
      trials that could alter the paradigm for CVD treatment and prevention in the
      general population. In this review, we will summarize the current evidence
      ascribing atheroprotective effects to RA pharmacotherapies.

PMID- 27032793
TI  - Mental Health Courts: Does Treatment Make a Difference?

PMID- 27032795
TI  - Protecting the Rights of Persons With Disabilities: An International Convention
      and Its Problems.
AB  - The Convention on the Rights of Persons with Disabilities, adopted by the United
      Nations in 2007, aims to protect the rights and dignity of persons with
      disabilities. However, several of its provisions are susceptible to
      interpretations that would negate traditional approaches to the protection of
      people with mental disorders. Guardianship, civil commitment, and even medical
      treatment of delirious patients appear to be precluded by the convention. This
      column describes the reactions to restrictive interpretations of the convention
      and lessons that can be learned for the development of similar documents. 

PMID- 27032796
TI  - Correction to Freidl et al.

PMID- 27032797
TI  - Perhaps I Touched the Minaret, or How Patient-Centered Care Remains a Dream.

PMID- 27032798
TI  - Psychiatric Pharmacists: Key Allies to Improve Antipsychotic Metabolic
      Monitoring.

PMID- 27032799
TI  - Implementation Academy Model for Integrating Behavioral Health Care for Service
      Members, Veterans, and Their Families.

PMID- 27032801
TI  - Metacontrast masking and attention do not interact.
AB  - Visual masking and attention have been known to control the transfer of
      information from sensory memory to visual short-term memory. A natural question
      is whether these processes operate independently or interact. Recent evidence
      suggests that studies that reported interactions between masking and attention
      suffered from ceiling and/or floor effects. The objective of the present study
      was to investigate whether metacontrast masking and attention interact by using
      an experimental design in which saturation effects are avoided. We asked
      observers to report the orientation of a target bar randomly selected from a
      display containing either two or six bars. The mask was a ring that surrounded
      the target bar. Attentional load was controlled by set-size and masking strength
      by the stimulus onset asynchrony between the target bar and the mask ring. We
      investigated interactions between masking and attention by analyzing two
      different aspects of performance: (i) the mean absolute response errors and (ii)
      the distribution of signed response errors. Our results show that attention
      affects observers' performance without interacting with masking. Statistical
      modeling of response errors suggests that attention and metacontrast masking
      exert their effects by independently modulating the probability of "guessing"
      behavior. Implications of our findings for models of attention are discussed.

PMID- 27032802
TI  - Identification and characterization of a novel bifunctional Delta(12)/Delta(15)
      fatty acid desaturase gene from Rhodosporidium kratochvilovae.
AB  - OBJECTIVES: To elucidate the biosynthesis pathway of linoleic acid and alpha
      linolenic acid in Rhodosporidium kratochvilovae YM25235 and investigate the
      correlation of polyunsaturated fatty acids with its cold adaptation. RESULTS: A
      1341 bp cDNA sequence, designated as RKD12, putatively encoding a Delta(12)
      desaturase was isolated from YM25235. Sequence analysis indicated that this
      sequence comprised a complete ORF encoding 446 amino acids of 50.6 kDa. The
      encoded amino acid sequence shared higher similarity to known fungal Delta(12)
      desaturases that are characteristic of three conserved histidine-rich motifs.
      RKD12 was further transformed into Saccharomyces cerevisiae INVScl for functional
      characterization. Fatty acid analysis showed the yeast transformants accumulated
      two new fatty acids: linoleic acid and alpha-linolenic acid. Furthermore, mRNA
      expression level of RKD12 and the content of linoleic acid and alpha-linolenic
      acid were increased significantly with the culture temperature downshift from 30
      to 15  degrees C, which might be helpful for the cold adaptation of YM25235.
      CONCLUSION: RKD12 is a novel bifunctional ?(12)/?(15)-desaturase gene, and the
      increased RKD12 mRNA expression level and PUFAs content at low temperature might
      be helpful for the cold adaptation of YM25235.

PMID- 27032803
TI  - Improving the management of Inherited Retinal Dystrophies by targeted sequencing
      of a population-specific gene panel.
AB  - Next-generation sequencing (NGS) has overcome important limitations to the
      molecular diagnosis of Inherited Retinal Dystrophies (IRD) such as the high
      clinical and genetic heterogeneity and the overlapping phenotypes. The purpose of
      this study was the identification of the genetic defect in 32 Spanish families
      with different forms of IRD. With that aim, we implemented a custom NGS panel
      comprising 64 IRD-associated genes in our population, and three disease
      associated intronic regions. A total of 37 pathogenic mutations (14 novels) were
      found in 73% of IRD patients ranging from 50% for autosomal dominant cases, 75%
      for syndromic cases, 83% for autosomal recessive cases, and 100% for X-linked
      cases. Additionally, unexpected phenotype-genotype correlations were found in 6
      probands, which led to the refinement of their clinical diagnoses. Furthermore,
      intra- and interfamilial phenotypic variability was observed in two cases.
      Moreover, two cases unsuccessfully analysed by exome sequencing were resolved by
      applying this panel. Our results demonstrate that this hypothesis-free approach
      based on frequently mutated, population-specific loci is highly cost-efficient
      for the routine diagnosis of this heterogeneous condition and allows the unbiased
      analysis of a miscellaneous cohort. The molecular information found here has aid
      clinical diagnosis and has improved genetic counselling and patient management. 

PMID- 27032804
TI  - Age differences in reactive strategies and execution time during choice stepping
      with visual interference.
AB  - PURPOSE: We aimed to explore the effects of visual interference from a flanker
      task on a reactive strategy and execution speed of choice stepping among young
      and older adults. METHODS: Twenty-two healthy young (21.9 +/- 1.4 years) and 21
      older participants (72.6 +/- 4.9 years) were instructed to execute forward
      stepping as quickly and accurately as possible on the side indicated by a central
      arrow (<-left vs. right->) of a visual cue during a neutral condition. During a
      flanker condition, participants were additionally required to ignore flanker
      arrows on each side of the central arrow (->->->->-> congruent or incongruent ->
      ><-->->). Errors in the direction of the initial weight transfer [anticipatory
      postural adjustment (APA) errors], step execution time, and divided phases
      (reaction, APA, and swing phases) were measured from the data of vertical force.
      RESULTS: Incongruence had larger effects on step execution times and APA phase in
      older adults than in young adults, while incongruence had smaller effects on
      reaction phase in older adults than in young adults. Step execution times were
      prolonged for trials with APA errors relative to trials without those in both
      groups. Only older adults showed that step execution times during trials with APA
      errors increased prominently in the incongruent condition as compared to the
      other conditions. CONCLUSION: Older adults might have a tendency to make hastier
      judgments, and might be vulnerable to potential motor program errors caused by an
      interference effect. Composite measurement of inhibition and stepping in a
      functional context may increase discriminative ability for age-related deficits
      in postural control.

PMID- 27032805
TI  - Unique activation of the quadriceps femoris during single- and multi-joint
      exercises.
AB  - PURPOSE: This study aimed to examine whether muscle activation of the quadriceps
      femoris differs between single- and multi-joint exercises, and to explore the
      factors resulting in muscle and exercise specificity in activation. METHODS:
      Eleven adults developed isometric hip extension torque gradually while
      maintaining submaximal isometric knee extension torque (Experiment 1). In
      Experiment 2, 15 men performed knee extension and leg press separately at
      intensities of 20, 40, 60 and 80 % of their one repetition maximum (1RM) load,
      and 14 men conducted leg press at intensities of 40 and 80 % of 1RM until
      exhaustion (Experiment 3). Muscle activation during exercises was measured using
      surface electromyography from the rectus femoris, vastus lateralis and medialis.
      RESULTS: The addition of isometric hip extension torque significantly decreased
      rectus femoris activation (Experiment 1). In Experiment 2, the rectus femoris
      activation was significantly higher during knee extension than during leg press,
      whereas no differences were observed in the vasti. The rectus femoris activation
      was not significantly different between leg press at 80 % and knee extension at
      20 % of 1RM. The results of Experiment 3 showed significant increases in vasti
      activation at both intensities, whereas rectus femoris activation did not change
      at 80 % of 1RM. CONCLUSION: The results revealed that even at high intensity, the
      rectus femoris activation during multi-joint exercise is low and does not
      increase with fatigue, unlike the vasti, and that the inter-muscle and inter
      exercise differences in activation depend on whether hip extension torque is
      exerted in the exercise.

PMID- 27032807
TI  - We need "healthy towns" across all of England.

PMID- 27032806
TI  - Effect of muscle length on voluntary activation of the plantar flexors in boys
      and men.
AB  - PURPOSE: The aim of the present study was to compare the effect of muscle length
      on the maximal voluntary activation level (VA) of the plantar-flexors between
      children and adults. METHODS: Fourteen boys (10.0 +/- 1.0 years) and fifteen men
      (24.6 +/- 4.2 years) performed 5-s maximal isometric voluntary contractions (MVC)
      of the plantar-flexor muscles at seven ankle angles [from 10 degrees  in dorsi
      flexion (DF) to 20 degrees  in plantar-flexion (PF); 0 degrees  = reference
      position; the angle between the plantar surface and leg is a right angle]. Single
      magnetic stimulations were delivered to the posterior tibial nerve during MVCs to
      determine VA. RESULTS: Results showed a higher absolute torque of the plantar
      flexor muscles at long (10 degrees  DF) than at short muscle length (20 degrees 
      PF) in men (89.4 +/- 19.4 vs. 46.8 +/- 17.0 N m, P < 0.001) and boys (44.9 +/-
      18.5 vs. 26.6 +/- 12.8 N m, P < 0.001). On average, VA was significantly higher
      in men than in boys (92.4 +/- 1.7 vs. 87.6 +/- 1.6 %, P < 0.05). However, no
      significant main effect of the ankle angle was observed on VA. CONCLUSIONS: The
      VA partly accounts for the plantar-flexors MVC torque difference between children
      and adults but is not affected by the muscle length changes in both groups.
      Therefore, VA cannot account for the shape of the torque-angle relationship on
      the plantar-flexor muscles.

PMID- 27032808
TI  - Factors associated with cognitive function in older adults in Mexico.
AB  - BACKGROUND: As populations age, cognitive decline and dementia pose significant
      burdens for societies and health care systems, including low- and middle-income
      countries such as Mexico. Minor age-related declines in cognitive function appear
      to represent a stable but heterogeneous phase in the continuum between normal
      cognitive ageing and dementia. Loss of cognitive function has impacts at societal
      and individual levels and understanding the risk factors can help provide a
      framework for health policies and interventions to target at-risk groups. DESIGN:
      A cohort of older Mexican adults (50+) from the World Health Organization's Study
      on global AGEing and adult health (WHO SAGE) was used to examine cognitive
      function, including a total of 2315 respondents, with 325 respondents aged 80
      years and older. Cognition was objectively evaluated using verbal recall, verbal
      fluency, forward digit span and backward digit span, with differences in an
      overall cognitive score assessed against sociodemographic variables, and
      associated factors using linear regression. RESULTS: The most significant
      predictors of poorer cognitive function were found to be older age (beta=-13.88),
      rural living (beta=-2.25), low income (beta=-8.28), self-reported severe or
      extreme memory difficulties (beta=-6.62), and difficulty with two or more
      activities of daily living (beta=-2.02). CONCLUSIONS: These findings can inform
      public health initiatives to address cognitive impairment in ageing populations
      in Mexico and other middle-income countries.

PMID- 27032810
TI  - Remote monitoring of building oscillation modes by means of real-time Mid
      Infrared Digital Holography.
AB  - Non-destructive measurements of deformations are a quite common application of
      holography but due to the intrinsic limits in the interferometric technique,
      those are generally confined only to small targets and in controlled environment.
      Here we present an advanced technique, based on Mid Infrared Digital Holography
      (MIR DH), which works in outdoor conditions and provides remote and real-time
      information on the oscillation modes of large engineering structures. Thanks to
      the long wavelength of the laser radiation, large areas of buildings can be
      simultaneously mapped with sub-micrometric resolution in terms of their amplitude
      and frequency oscillation modes providing all the modal parameters vital for all
      the correct prevention strategies when the functionality and the health status of
      the structures have to be evaluated. The existing experimental techniques used to
      evaluate the fundamental modes of a structure are based either on seismometric
      sensors or on Ground-based Synthetic Aperture Radar (GbSAR). Such devices have
      both serious drawbacks, which prevent their application at a large scale or in
      the short term. We here demonstrate that the MIR DH based technique can fully
      overcome these limitations and has the potential to represent a breakthrough
      advance in the field of dynamic characterization of large structures. 

PMID- 27032809
TI  - Determinants of unmet needs for healthcare and sexual health counselling among
      Ugandan university students with same-sex sexuality experience.
AB  - BACKGROUND: Research from sub-Saharan Africa has shown that persons with same-sex
      sexuality experience are at elevated risk for ill health due to sexual risk
      taking, stigma, and discrimination. However, studies of healthcare seeking among
      young people in this region with same-sex sexuality experience are limited.
      OBJECTIVE: To identify determinants of unmet healthcare and sexual health
      counselling needs, respectively, among Ugandan university students with
      experience of same-sex sexuality. DESIGN: In 2010, 1,954 Ugandan university
      students completed a questionnaire assessing socio-demographic factors, mental
      health, alcohol usage, sexual behaviours, and healthcare seeking. The study
      population consisted of those 570 who reported ever being in love with, sexually
      attracted to, sexually fantasised about, or sexually engaged with someone of the
      same sex. RESULTS: Findings showed that 56% and 30% reported unmet healthcare and
      sexual health counselling needs, respectively. Unmet healthcare needs were
      associated with poor mental health and exposure to sexual coercion (OR 3.9, 95%
      confidence intervals [CI]: 2.7-5.7; OR 2.0, 95% CI: 1.3-3.0, respectively). Unmet
      sexual health counselling needs were significantly associated with poor mental
      health (OR 3.2, 95% CI: 2.1-4.8), exposure to sexual coercion (OR 2.6, 95% CI:
      1.7-3.9), frequent heavy episodic drinking (OR 3.3, 95% CI: 1.9-5.8), and number
      of sexual partners (OR 1.9, 95% CI: 1.04-3.3). The associations between poor
      mental health, sexual coercion, and unmet healthcare needs (AOR 4.2, 95% CI: 2.1
      8.5; AOR 2.8, 95% CI: 1.3-5.8) and unmet needs for sexual health counselling (AOR
      3.3, 95% CI: 1.6-7.1; AOR 2.7, 95% CI: 1.4-5.4) persisted after adjustment for
      socio-demographic factors, number of sexual partners, and frequent heavy episodic
      drinking. CONCLUSIONS: These findings indicate that exposure to sexual coercion
      and poor mental health may influence healthcare seeking behaviours of same-sex
      sexuality experienced students. Targeted interventions that integrate mental
      health and trauma response are critical to meet the health needs of this
      population.

PMID- 27032811
TI  - "Shaken baby" expert with unconventional views struck off.

PMID- 27032812
TI  - An open comparative study of nail drilling as adjunctive treatment for toenail
      onychomycosis (.).
AB  - Introduction Novel treatment regimens are being developed to improve drug
      penetration through the nail plate. This study investigated the efficacy of nail
      drilling regimens for the treatment of onychomycosis. Methods Participants were
      assigned to holes with combination (oral plus topical terbinafine) therapy (Group
      1), holes with topical terbinafine (Group 2) or topical terbinafine only (Group
      3). Measurement of clear nail and mycology was performed at baseline and at weeks
      4, 10, 16, 22 and 28. Mixed linear models were used to compare mean percent clear
      nail. Mycological cure rates were also tabulated for each group. Tolerability and
      adverse events were documented. Results Ninety-eight participants were enrolled
      (106 nails). Both groups with holes had significantly higher percentage of clear
      nail compared with topical terbinafine alone. Although no significant difference
      between the two groups where holes were drilled in the nail plate, Group 1
      demonstrated improvement over Group 3 earlier than Group 2 (visit 2 versus visit
      4). Group 1 also had the highest mycological cure rates. Conclusion Treatment
      with holes plus topical terbinafine produces significantly greater improvement in
      toenails' appearance and higher mycological cure rates compared to treating the
      dorsal aspect of the nail plate with topical terbinafine alone. 

PMID- 27032813
TI  - New hybrid voxelized/analytical primitive in Monte Carlo simulations for medical
      applications.
AB  - Monte Carlo simulations (MCS) applied in particle physics play a key role in
      medical imaging and particle therapy. In such simulations, particles are
      transported through voxelized phantoms derived from predominantly patient CT
      images. However, such voxelized object representation limits the incorporation of
      fine elements, such as artificial implants from CAD modeling or anatomical and
      functional details extracted from other imaging modalities. In this work we
      propose a new hYbrid Voxelized/ANalytical primitive (YVAN) that combines both
      voxelized and analytical object descriptions within the same MCS, without the
      need to simultaneously run two parallel simulations, which is the current gold
      standard methodology. Given that YVAN is simply a new primitive object, it does
      not require any modifications on the underlying MC navigation code. The new
      proposed primitive was assessed through a first simple MCS. Results from the YVAN
      primitive were compared against an MCS using a pure analytical geometry and the
      layer mass geometry concept. A perfect agreement was found between these
      simulations, leading to the conclusion that the new hybrid primitive is able to
      accurately and efficiently handle phantoms defined by a mixture of voxelized and
      analytical objects. In addition, two application-based evaluation studies in
      coronary angiography and intra-operative radiotherapy showed that the use of YVAN
      was 6.5% and 12.2% faster than the layered mass geometry method, respectively,
      without any associated loss of accuracy. However, the simplification advantages
      and differences in computational time improvements obtained with YVAN depend on
      the relative proportion of the analytical and voxelized structures used in the
      simulation as well as the size and number of triangles used in the description of
      the analytical object meshes. 

PMID- 27032814
TI  - Clinical response and tolerability of fampridine in clinical practice.
AB  - BACKGROUND: Gait disorder is very prevalent in multiple sclerosis. After 15 years
      of disease progression, 50% of patients need assistive devices for walking.
      MATERIALS & METHODS: We performed a multicenter observational study, including
      multiple sclerosis patients with an Expanded Disability Status Scale score
      between 4.0 and 7.0, normal kidney function and no previous history of seizures.
      RESULTS: The study sample comprised 138 patients with average age of 50.3 years
      median Expanded Disability Status Scale of 6.0. After treatment, a significant
      reduction was observed in both the Timed 25-Foot Walk test (baseline, 20.3 s; 14
      days, 13.2 s; p < 0.001; 3 months, 12.1 s; p < 0.001) and the 12-Item Multiple
      Sclerosis Walking Scale score (baseline, 82.3; 14 days, 59.4; p < 0.001; 3
      months, 57.2; p < 0.001). Adverse events were recorded in 39.9% of patients.

PMID- 27032816
TI  - Developmental venous anomaly: a rare cause of cerebellar ataxia.

PMID- 27032815
TI  - Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of
      Mouse Revealed by a High-throughput Targeted Metabolomics Approach.
AB  - Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in
      hepatotoxicity and neurobehavioral effects in animals. The metabolome, which
      serves as a connection among transcriptome, proteome and toxic effects, provides
      pathway-based insights into effects of PFOA. Since understanding of changes in
      the metabolic profile during hepatotoxicity and neurotoxicity were still
      incomplete, a high-throughput targeted metabolomics approach (278 metabolites)
      was used to investigate effects of exposure to PFOA for 28 d on brain and liver
      of male Balb/c mice. Results of multivariate statistical analysis indicated that
      PFOA caused alterations in metabolic pathways in exposed individuals. Pathway
      analysis suggested that PFOA affected metabolism of amino acids, lipids,
      carbohydrates and energetics. Ten and 18 metabolites were identified as potential
      unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain,
      PFOA affected concentrations of neurotransmitters, including serotonin, dopamine,
      norepinephrine, and glutamate in brain, which provides novel insights into
      mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids
      revealed involvement of beta-oxidation and biosynthesis of saturated and
      unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in
      metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation
      response in liver. These results provide insight into the mechanism and
      biomarkers for PFOA-induced effects. 

PMID- 27032817
TI  - Distinct disruptions of resting-state functional brain networks in familial and
      sporadic schizophrenia.
AB  - Clinical and brain structural differences have been reported between patients
      with familial and sporadic schizophrenia; however, little is known about the
      brain functional differences between the two subtypes of schizophrenia. Twenty
      six patients with familial schizophrenia (PFS), 26 patients with sporadic
      schizophrenia (PSS) and 26 healthy controls (HC) underwent a resting-state
      functional magnetic resonance imaging. The whole-brain functional network was
      constructed and analyzed using graph theoretical approaches. Topological
      properties (including global, nodal and edge measures) were compared among the
      three groups. We found that PFS, PSS and HC exhibited common small-world
      architecture of the functional brain networks. However, at a global level, only
      PFS showed significantly lower normalized clustering coefficient, small
      worldness, and local efficiency, indicating a randomization shift of their brain
      networks. At a regional level, PFS and PSS disrupted different neural circuits,
      consisting of abnormal nodes (increased or decreased nodal centrality) and edges
      (decreased functional connectivity strength), which were widely distributed
      throughout the entire brain. Furthermore, some of these altered network measures
      were significantly correlated with severity of psychotic symptoms. These results
      suggest that familial and sporadic schizophrenia had segregated disruptions in
      the topological organization of the intrinsic functional brain network, which may
      be due to different etiological contributions. 

PMID- 27032818
TI  - Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses
      autoantibody-induced inflammation in vivo.
AB  - Neutrophils are terminally differentiated cells with limited transcriptional
      activity. The biological function of their gene expression changes is poorly
      understood. CARD9 regulates transcription during antifungal immunity but its role
      in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates
      pro-inflammatory chemokine/cytokine but not lipid mediator release during non
      infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody
      induced arthritis and dermatitis in mice. Neutrophil-specific deletion of CARD9
      is sufficient to induce that phenotype. Card9(-/-) neutrophils show defective
      immune complex-induced gene expression changes and pro-inflammatory
      chemokine/cytokine release but normal LTB4 production and other short-term
      responses. In vivo deletion of CARD9 reduces tissue levels of pro-inflammatory
      chemokines and cytokines but not LTB4. The CARD9-mediated signalling pathway
      involves Src-family kinases, Syk, PLCgamma2, Bcl10/Malt1 and NFkappaB.
      Collectively, CARD9-mediated gene expression changes within neutrophils play
      important roles during non-infectious inflammation in vivo and CARD9 acts as a
      divergence point between chemokine/cytokine and lipid mediator release. 

PMID- 27032819
TI  - Human DNA polymerase alpha in binary complex with a DNA:DNA template-primer.
AB  - The Polalpha/primase complex assembles the short RNA-DNA fragments for priming of
      lagging and leading strand DNA replication in eukaryotes. As such, the Polalpha
      polymerase subunit encounters two types of substrates during primer synthesis: an
      RNA:DNA helix and a DNA:DNA helix. The engagement of the polymerase subunit with
      the DNA:DNA helix has been suggested as the of basis for primer termination in
      eukaryotes. However, there is no structural information on how the Polalpha
      polymerase subunit actually engages with a DNA:DNA helix during primer synthesis.
      We present here the first crystal structure of human Polalpha polymerase subunit
      in complex with a DNA:DNA helix. Unexpectedly, we find that portion of the
      DNA:DNA helix in contact with the polymerase is not in a B-form but in a hybrid A
      B form. Almost all of the contacts observed previously with an RNA primer are
      preserved with a DNA primer--with the same set of polymerase residues tracking
      the sugar-phosphate backbone of the DNA or RNA primer. Thus, rather than loss of
      specific contacts, the free energy cost of distorting DNA from B- to hybrid A-B
      form may augur the termination of primer synthesis in eukaryotes.

PMID- 27032820
TI  - Putting translational science on to a global stage.
AB  - Global collaboration in translational science promises to accelerate the
      discovery, development and dissemination of new medical interventions. Here, we
      introduce a new international collaboration of translational science
      organizations and highlight our initial strategy to reduce or remove bottlenecks
      in translation.

PMID- 27032821
TI  - Deuterated drugs draw heavier backing.

PMID- 27032822
TI  - European Lead Factory hits its stride.

PMID- 27032825
TI  - Patent watch: Modulating the human microbiome with live biotherapeutic products:
      intellectual property landscape.

PMID- 27032826
TI  - Market watch: Upcoming market catalysts in Q2 2016.

PMID- 27032827
TI  - Arthur Caplan.

PMID- 27032828
TI  - The non-small-cell lung cancer drug market.

PMID- 27032829
TI  - Drug delivery: Nanoparticles improve profile of molecularly targeted cancer drug.

PMID- 27032830
TI  - Antifungals: Protein-protein interaction inhibitor tackles drug resistance.

PMID- 27032831
TI  - Antimalarials: Novel proteasome inhibitor combats malaria.

PMID- 27032832
TI  - Autoimmunity: Nanoparticles engineered for antigen-specific immunotherapy.

PMID- 27032835
TI  - Infectious diseases: Cattle engineered to produce human antibodies against
      coronavirus.

PMID- 27032839
TI  - Where are the males? Diversity, proportionality and Health Sciences admissions.

PMID- 27032838
TI  - Effect of alternating bioremediation and electrokinetics on the remediation of n
      hexadecane-contaminated soil.
AB  - This study demonstrated the highly efficient degradation of n-hexadecane in soil,
      realized by alternating bioremediation and electrokinetic technologies. Using an
      alternating technology instead of simultaneous application prevented competition
      between the processes that would lower their efficiency. For the consumption of
      the soil dissolved organic matter (DOM) necessary for bioremediation by
      electrokinetics, bioremediation was performed first. Because of the utilization
      and loss of the DOM and water-soluble ions by the microbial and electrokinetic
      processes, respectively, both of them were supplemented to provide a basic carbon
      resource, maintain a high electrical conductivity and produce a uniform
      distribution of ions. The moisture and bacteria were also supplemented. The
      optimal DOM supplement (20.5 mg.kg(-1) glucose; 80-90% of the total natural DOM
      content in the soil) was calculated to avoid competitive effects (between the DOM
      and n-hexadecane) and to prevent nutritional deficiency. The replenishment of the
      water-soluble ions maintained their content equal to their initial
      concentrations. The degradation rate of n-hexadecane was only 167.0 mg.kg(-1).d(
      1) (1.9%, w/w) for the first 9 days in the treatments with bioremediation or
      electrokinetics alone, but this rate was realized throughout the whole process
      when the two technologies were alternated, with a degradation of 78.5% +/- 2.0%
      for the n-hexadecane after 45 days of treatment. 

PMID- 27032840
TI  - Unpacking the new proposed regulations for South African traditional health
      practitioners.
AB  - South Africa (SA) has legislation that regulates almost all of its healthcare
      systems. The Traditional Health Practitoners Act finally provides legitimisation
      of an overwhelmingly popular indigenous healthcare system. However, as a
      consequence of the legal acknowledgement of traditional health practitioners,
      traditional medicine products must now also be brought under regulatory measures.
      If traditional medicines are to be prescribed, marketed and sold as part of a
      healthcare system recognised under SA law, they must meet the same stringent
      standards. 

PMID- 27032841
TI  - A call to action: Addressing the reproductive health needs of women with drug
      resistant tuberculosis.
AB  - Although there is substantial risk to maternal and neonatal health in the
      situation of pregnancy during treatment for rifampicin-resistant tuberculosis (RR
      TB), there is little evidence to guide clinicians as to how to manage this
      complexity. Of the 49 680 patients initiated on RR-TB treatment from 2009 to 2014
      in South Africa, 47% were women and 80% of them were in their reproductive years
      (15 - 44). There is an urgent need for increased evidence of the safety of RR-TB
      treatment during pregnancy, increased access to contraception during RR-TB
      treatment, and inclusion of reproductive health in research on the prevention and
      treatment of TB. 

PMID- 27032842
TI  - A multifaceted hospital-wide intervention increases hand hygiene compliance.
AB  - BACKGROUND: Hand hygiene is an important and basic practice that should be used
      by all healthcare staff to protect both themselves and their patients against
      infection. Unfortunately hand hygiene compliance remains poor. OBJECTIVE: To show
      an improvement in hand hygiene compliance using a multifaceted approach. METHODS:
      This was a quasiexperimental pre-post intervention study design with a number of
      standardised interventions to promote hand hygiene. The World Health Organization
      hand hygiene multimodal (five-step) intervention approach was used. The study ran
      from June 2015 to August 2015 in 11 selected wards of a 975-bed tertiary and
      quaternary care public hospital (Groote Schuur Hospital, Cape Town, South
      Africa). The outcome was to assess improvement in hand hygiene compliance monthly
      over the 3 months, compared with non-intervention wards and compared with the
      wards' own performance measured in 2014. The study included both descriptive and
      analytical components. RESULTS: Post intervention, hand hygiene compliance showed
      a statistically significant improvement for before patient contact from 34% in
      2014 to 76% in 2015 (p<0.05) and for after patient contact from 47% in 2014 to
      82% in 2015 (p<0.05). CONCLUSION: The intervention improved hand hygiene
      compliance and can easily be replicated in other wards, resulting in sustaining a
      culture of hand hygiene improvement and behavioural change throughout the
      hospital.

PMID- 27032843
TI  - Intracranial complications of Serratia marcescens infection in neonates.
AB  - Even though Serratia marcescens is not one of the most common causes of infection
      in neonates, it is associated with grave morbidity and mortality. We describe the
      evolution of brain parenchymal affectation observed in association with S.
      marcescens infection in neonates. This retrospective case series details brain
      ultrasound findings of five neonates with hospital-acquired S. marcescens
      infection. Neonatal S. marcescens infection with or without associated meningitis
      can be complicated by brain parenchymal affectation, leading to cerebral abscess
      formation. It is recommended that all neonates with this infection should undergo
      neuro-imaging more than once before discharge from hospital; this can be achieved
      using bedside ultrasonography.

PMID- 27032844
TI  - Biofilms associated with bowel necrosis: A newly recognised phenomenon in
      infants.
AB  - BACKGROUND: A biofilm is defined as a collection of organisms attached to a
      surface and surrounded by a matrix. OBJECTIVE: To present three cases in which
      bowel necrosis coexisted with biofilm. METHODS: The medical records,
      bacteriological findings and tissue biopsies from three infants with bowel
      necrosis who subsequently died from sepsis were analysed. Tissue sent for
      histological evaluation was prepared for light microscopy. Haematoxylin and eosin
      (H&E), Sandiford and Alcian blue/periodic acid Schiff (ABPAS) stains were
      performed. Tissue samples were ex-waxed for electron microscopy in one case.
      RESULTS: The three patients described all had necrotic bowel at laparotomy, all
      cultured Klebsiella pneumoniae from peritoneal pus swabs, and all died despite
      appropriate antibiotics. All specimens showed varying degrees of bowel necrosis
      and an organising acute peritoneal reaction. In addition, all showed colonies of
      Gram-negative bacteria within a mucopolysaccharide matrix. CONCLUSIONS: The
      identification of biofilms in necrotic bowel has raised questions regarding their
      clinical implications. Further studies are needed to evaluate all resected
      necrotic bowel for biofilms and the clinical implications of this finding.

PMID- 27032845
TI  - A child's potential claim for negligent misdiagnosis: The case of H v Fetal
      Assessment Centre.
AB  - South African law recognises a financial claim against a health provider for
      negligently failing to advise an expectant mother that she might give birth to a
      child suffering from a severe health condition or congenital disability. In
      December 2014, the Constitutional Court handed down a judgment that could lead to
      financial claims by the child, who was subsequently born with a severe health
      condition or disability. This judgment thus creates a framework to legally
      recognise a claim by a child whose current health condition was negligently
      misdiagnosed before birth. The contents and effects of the judgment are discussed
      in this article. 

PMID- 27032846
TI  - The impact of the Medicines Control Council backlog and fast-track review system
      on access to innovative and new generic and biosimilar medicines of public health
      importance in South Africa.
AB  - The fast-track registration policy of the South African National Department of
      Health allows for rapid registration of new medicines of public health importance
      and of all medicines on the Essential Medicines List, most of which are generics.
      No limit is placed on the number of generic brands of a medicine that can be
      submitted for fast-track registration. This, together with resource constraints
      at the regulator, may delay access to important new medicines, new fixed-dose
      combinations of critical medicines or affordable versions of biological medicines
      (biosimilars). One reason for not limiting the number of fast-track generic
      applications was to promote price competition among generic brands. We found this
      not to be valid, since market share correlated poorly with price. Generic brands
      with high market share were, mostly, those that were registered first. We propose
      that the number of generic brands accepted for fast-tracking be limited to not
      more than seven per medicine. 

PMID- 27032847
TI  - Oribital apex syndrome caused by aspergilloma in an immunocompromised patient
      with cutaneous lymphoma: A case report of a rare entity.
AB  - A 57-year-old man with a history of chemotherapy because of cutaneous lymphoma
      presented with an orbital apex syndrome. The cranial computed tomography scan
      revealed a tumour in the orbital apex, extending intradurally. With a suspected
      diagnosis of a neoplastic lesion, the patient underwent orbital surgery with
      optic nerve decompression. Histology revealed an aspergilloma. No other foci were
      seen and treatment with antifungals was started. In immunocompromised patients
      with intracranial tumours, infection is always a major consideration in the
      differential diagnosis, even if the reason for immunosuppression (in this case
      chemotherapy) dates back several months. Misdiagnosing an orbital apex lesion as
      a cancer and treating patients primarily with corticosteroids can be life
      threatening. Removal or biopsy of such lesions is essential in further treatment
      since antifungals have to be administered as fast as possible. 

PMID- 27032849
TI  - Where do children die and what are the causes? Under-5 deaths in the Metro West
      geographical service area of the Western Cape, South Africa, 2011.
AB  - BACKGROUND: Accurate child mortality data are essential to plan health
      interventions to reduce child deaths. OBJECTIVES: To review the deaths of
      children aged <5 years during 2011 in the Metro West geographical service area
      (GSA) of the Western Cape Province (WC), South Africa, from routine data sources.
      METHODS: A retrospective study of under-5 deaths in the Metro West GSA was done
      using the WC Local Mortality Surveillance System (LMSS), the Child Healthcare
      Problem Identification Programme (Child PIP) and the Perinatal Problem
      Identification Programme (PPIP), and linking where possible. RESULTS: The LMSS
      reported 700 under-5 deaths, Child PIP 99 and PPIP 252, with an under-5 mortality
      rate of 18 deaths per 1 000 live births. The leading causes of death were
      pneumonia (25%), gastroenteritis (10%), prematurity (9%) and injuries (9%). There
      were 316 in-hospital deaths (45%) and 384 out-of-hospital deaths (55%). Among
      children aged <1 year, there were significantly more pneumonia deaths out of
      hospital than in hospital (144 (49%) v. 16 (6%); p<0.001). Among children aged 1 
      4 years there were significantly more injury-related deaths out of hospital than
      in hospital (43 (47%) v. 4 (9%); p<0.001). In 56 (15%) of the cases of out-of
      hospital death the child had visited a public healthcare facility within 1 week
      of death. Thirty-six (64%) of these children had died of pneumonia or
      gastroenteritis. CONCLUSIONS: Health interventions targeted at reducing under-5
      deaths from pneumonia, gastroenteritis, prematurity and injuries need to be
      implemented across the service delivery platform in the Metro West GSA. It is
      important to consider all routine data sources in the evaluation of child
      mortality.

PMID- 27032848
TI  - Autoimmune progesterone dermatitis: Case report with history of urticaria,
      petechiae and palpable pinpoint purpura triggered by medical abortion.
AB  - Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised
      endogenous progesterone levels that occur during the luteal phase of the
      menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations
      develop cyclically during the luteal phase of the menstrual cycle when
      progesterone levels are elevated. APD symptoms usually start 3 - 10 days before
      menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old
      woman presented with urticaria, petechiae and palpable pinpoint purpura lesions
      of the legs, forearms, neck and buttocks 1 week prior to her menses starting and
      2 months after a medical abortion. She was diagnosed with allergic contact
      dermatitis and topical steroids were prescribed. Her skin conditions did not
      improve and were associated with her menstrual cycle. We performed an intradermal
      test using progesterone, which was positive. She was treated with oral
      contraceptive pills and the symptoms were resolved. This is a typical case of APD
      triggered by increased sensitivity to endogenous progesterone induced a few
      months after medical abortion. 

PMID- 27032850
TI  - Antiretroviral therapy programme outcomes in Tshwane district, South Africa: A 5
      year retrospective study.
AB  - BACKGROUND: Scaling up of antiretroviral therapy (ART) in South Africa (SA) has
      resulted in an increase in the number of patients on the national ART programme
      and an increased workload for ART service providers nationwide. OBJECTIVES: To
      ascertain patient retention on ART after 5 years on treatment in one district of
      Gauteng Province, SA, establish the number of patients who remained alive on ART
      after 5 years of treatment, and identify patient-related factors that contributed
      towards the outcome of each indicator. METHODS: A retrospective cohort study of
      patients initiated on highly active antiretroviral therapy (HAART) between
      January and March 2007 was carried out. A sample of 381 patients was randomly
      selected from 1 004 records, and their records were reviewed for visits over the
      previous 60 months. Summary statistics, Pearson's chi2 test and linear regression
      tests were performed. RESULTS: Of 381 patients, 156 (40.9%) remained alive and
      active on HAART at their initial sites. The overall mortality rate was 5.0% and
      the rate of long-term retention in care was 57.4%, excluding those transferred to
      another site. After 6 months on HAART the mean rise in CD4 count was 113
      cells/uL, and after 60 months it was 288 cells/uL. Viral load suppression to <400
      copies/mL was achieved in 74.0% of patients at 6 months and 91.0% at 60 months.
      CONCLUSIONS: Immunological and virological outcomes after 5 years on treatment
      were good. Both these positive outcomes showed that the ART programme was a
      success. Improved data quality and patient follow-up will further strengthen
      programme outcomes.

PMID- 27032851
TI  - Clinician compliance with laboratory monitoring and prescribing guidelines in HIV
      1-infected patients receiving tenofovir.
AB  - BACKGROUND: Tenofovir is part of the preferred first-line regimen for HIV
      infected patients in South Africa (SA), but is associated with kidney toxicity.
      SA antiretroviral therapy (ART) guidelines recommend creatinine monitoring at
      baseline (ART start) and at 3, 6 and 12 months, and substituting tenofovir with
      zidovudine, stavudine or abacavir should creatinine clearance (CrCl) decrease to
      <50 mL/min. OBJECTIVE: To assess clinician compliance with tenofovir monitoring
      and prescribing guidelines. METHODS: We described the proportion of adult
      patients on tenofovir-based first-line ART who were screened for baseline renal
      impairment, were monitored according to the SA antiretroviral treatment
      guidelines, and were switched from tenofovir if renal function declined. RESULTS:
      We included 13 168 patients who started ART from 2010 to 2012. Creatinine
      concentrations were recorded in 11 712 (88.9%) patients on tenofovir at baseline,
      9 135/11 657 (78.4%) at 3 months, 5 426/10 554 (51.4%) at 6 months, and 5 949/ 8
      421 (70.6%) at 12 months. At baseline, 227 (1.9%) started tenofovir despite a
      CrCl <50 mL/min. While on tenofovir, 525 patients had at least one CrCl of <50
      mL/min. Of 382 patients with >=3 months' follow-up after a CrCl <50 mL/min, 114
      (29.8%) stopped tenofovir within 3 months. Clinicians were more likely to stop
      tenofovir in patients with lower CrCl and CD4 count. Of 226 patients who
      continued to receive tenofovir and had further CrCls available, 156 (69.0%) had a
      CrCl >=50 mL/min at their next visit. CONCLUSIONS: Creatinine monitoring is
      feasible where access to laboratory services is good. Kidney function recovered
      in most patients who continued to receive tenofovir despite a CrCl <50 mL/min.
      Further research is needed to determine how best to monitor renal function with
      tenofovir in resource-limited settings.

PMID- 27032852
TI  - The S'Khokho 'bushcan' initiative: Kick a bush and condoms fall out.
AB  - BACKGROUND: People living in rural areas have limited access to condoms owing to
      distance, cost and time involved in travelling to public health facilities,
      around which most condom distribution efforts are centralised. OBJECTIVE: In an
      effort to increase access to condoms in these areas, we explored the feasibility
      and efficacy of condom distribution by placing 'condocans' on trees along
      informal footpaths used by residents. METHODS: From October 2012, steel
      condocans, typically seen in clinic settings, were erected on trees along
      pathways in bushy areas with high levels of foot traffic at several rural
      locations in the Umgungundlovu district of KwaZulu-Natal Province, South Africa
      (SA). Because of their location, the condocans were referred to as 'bushcans'.
      Condom uptake was closely monitored, and the bushcans were restocked when
      necessary. RESULTS: Following the introduction of the bushcans, male condom
      distribution increased by 237% from October 2012 to December 2012. Condom
      distribution in these areas increased on average by 187% from October 2012 to
      October 2015, with more than 408 000 condoms distributed over the 3-year period
      using the bushcans alone. Discussions with residents revealed that they were
      pleased about the increased access to condoms via the bushcans, and they
      recommended other areas for potential implementation of this initiative.
      CONCLUSIONS: The bushcan initiative highlighted the fact that condoms are not as
      easily accessible to all South Africans as is often thought. By providing access
      to condoms in a discreet and convenient manner, the bushcans have the potential
      to increase access to condoms in other rural and periurban areas in SA where
      communities face similar barriers to access.

PMID- 27032853
TI  - Piloting a national laboratory electronic programme status reporting system in
      Ekurhuleni health district, South Africa.
AB  - BACKGROUND: The National Health Laboratory Service (NHLS) performs ~4 million CD4
      tests per annum for the public health sector at 61 CD4 testing laboratories
      across South Africa. Currently, CD4 laboratory data captured do not differentiate
      between antiretroviral treatment (ART) and pre-ART care. METHODS: A cross
      sectional study was undertaken to evaluate a redesigned Comprehensive Care,
      Management and Treatment of HIV and AIDS (CCMT) request form, incorporating a two
      tick collection procedure linking the CD4 test request to patient CCMT programme
      status. Field testing was undertaken at three health facilities, where healthcare
      personnel were required to capture whether the CD4 count requested was a 'first
      ever CD4', 'CD4 taken previously, not yet in ART care' or 'in ART care'. All data
      were extracted from the NHLS Corporate Data Warehouse and analysed using
      Microsoft Excel and Stata-12. RESULTS: A substantial increase in the number of
      request forms with a CCMT programme status (28.1% v. 84.4%) was reported pre- and
      post-implementation. Post-implementation data (N=1 004) revealed that 30.8%
      patients were ART naive ('first-ever CD4'), with 7.4% 'not yet on ART' (median
      CD4 counts of 150 and 328 cells/uL, respectively). Patients on ART comprised
      61.9% of the study group (median CD4 count ~346 cells/uL). Sixty percent of
      patients were aged between 30 and 44 years, and females predominated (male/female
      ratio 0.7:1). CONCLUSIONS: A simple modification to the CCMT request form can
      successfully facilitate collection of programme status. For national
      implementation, it would be advantageous to have a unique patient identifier to
      further enhance laboratory-based programmatic monitoring and evaluation.

PMID- 27032854
TI  - A deadly combination - HIV and diabetes mellitus: Where are we now?
AB  - BACKGROUND: The combination of HIV infection and diabetes mellitus (DM)
      represents a collision of two chronic conditions. Both HIV and DM increase the
      risk of developing tuberculosis (TB). Health resources in developing countries
      are already under strain as a result of the TB epidemic and poor diabetic control
      would further worsen this epidemic. Optimal diabetic control provides one avenue
      of curbing the TB epidemic in developing countries. OBJECTIVES: To establish if
      there is a difference in blood pressure, lipid and glycaemic control and
      complications between HIV-infected and uninfected diabetic patients; and to
      compare characteristics among HIV-infected diabetic patients between those with
      optimal and sub- optimal glycaemic control. METHODS: This was a retrospective
      chart review of all patients who visited the Edendale Hospital diabetic clinic,
      Pietermaritzburg, from 1 October 2012 to 30 September 2013. RESULTS: There were
      statistically significant differences noted in the following parameters between
      HIV-infected and uninfected diabetic patients: (i) mean HbA1c% (11.08% v. 10.14%,
      respectively); (ii) nephropathy defined by proteinuria (25.66% v. 15.43%); (iii)
      neuropathy (48.68% v. 42.10%); and (iv) Kidney Disease Outcomes Quality
      Initiative (KDOQI) stage >=2 chronic kidney disease (30.87% v. 41.67%). There
      were no significant differences noted in the percentage of patients achieving the
      following target parameters between the two cohorts: (i) blood pressure (42.11%
      v. 35.62%); (ii) total cholesterol (36.84% v. 34.67%); and (iii) triglycerides
      (42.76% v. 40.19%). Within the HIV-infected diabetic cohort 85.23% displayed
      suboptimal glycaemic control. A significant percentage of HIV-infected diabetic
      patients on antiretroviral (ARV) therapy (89.36%) had suboptimal glycaemic
      control. HIV-infected female diabetic patients showed a significant increased
      waist circumference when compared with their HIV-uninfected counterparts.
      CONCLUSION: HIV-infected diabetic patients had significantly poorer blood sugar
      control and a higher incidence of neuropathy and nephropathy (when defined by
      overt proteinuria). There was a non-significant difference noted between the HIV
      infected and uninfected diabetic patients with regard to blood pressure and lipid
      control. The majority of HIV-infected patients on ARVs failed to achieve target
      glycaemic control. Obesity remains a global challenge, as noted in both the HIV
      infected and uninfected diabetic patients.

PMID- 27032857
TI  - The other side of surveillance: Monitoring, application, and integration of
      tuberculosis data to guide and evaluate programme activities in South Africa.
AB  - BACKGROUND: The importance of using surveillance data to monitor and evaluate
      programme activities has been emphasised in international policies for
      tuberculosis (TB) control. OBJECTIVES: A survey was conducted to assess the use
      of TB surveillance data to monitor and guide TB programme activities in South
      Africa (SA). METHODS: As part of an evaluation of the SA national TB surveillance
      system, semi-structured interviews were conducted among TB staff at health
      facilities and offices in three provinces. At each site, all persons involved
      with TB care, management and surveillance were invited to participate. RESULTS:
      At least one person (range 1 - 4) was interviewed at 47/54 health facilities
      (87.0%), 11/13 subdistrict and district TB offices (84.6%), 2/3 provincial TB
      offices (66.7%), and at the national level (1/1, 100.0%). Of 119 TB staff, 64.7%
      recognised the purpose of TB surveillance as guiding programme planning,
      implementation and evaluation. However, only 16.0% reported using data to measure
      disease burden, 8.4% to monitor trends, and 9.2% to inform resource allocation.
      The majority reported using TB management tools provided by the national
      programme, but 44.5% also described using additional tools. Personnel mentioned
      the need for dedicated surveillance staff, training on recording and reporting,
      improved computer access, and methods to apply information from surveillance data
      to the programme. CONCLUSIONS: The majority of TB staff understood the purpose of
      surveillance but did not routinely use data to guide programme planning,
      implementation and evaluation. Training and supporting TB staff to utilise
      surveillance data will help improve the TB surveillance system.

PMID- 27032858
TI  - A randomised controlled trial comparing oxytocin and oxytocin + ergometrine for
      prevention of postpartum haemorrhage at caesarean section.
AB  - BACKGROUND: Globally 166 000 women die annually as a result of obstetric
      haemorrhage. More than 50% of these deaths occur in sub-Saharan Africa. Uterine
      atony is the commonest cause of severe postpartum haemorrhage (PPH). Bleeding at
      or after caesarean section (CS) is responsible for >30% of maternal deaths due to
      obstetric haemorrhage in South Africa (SA). OBJECTIVE: To compare oxytocin alone
      with oxytocin + ergometrine in terms of primary prophylaxis for PPH at the time
      of CS. METHODS: This was a double-blind randomised controlled interventional
      study comparing oxytocin with oxytocin + ergometrine administered during CS.
      Patients were randomised to receive oxytocin alone intravenously as a bolus or
      oxytocin + ergometrine intramuscularly, with the placebo being an injection of
      sterile water. The study population consisted of women undergoing CS at Kalafong
      Provincial Tertiary Hospital in Atteridgeville, Gauteng, SA. RESULTS: Five
      hundred and forty women were randomised and data for 416 women, of whom 214
      received oxytocin and 202 oxytocin + ergometrine, were available for analysis. In
      the oxytocin group 19 women (8.9%) required blood transfusion, compared with
      seven (3.5%) in the oxytocin + ergometrine group (p=0.01; relative risk = 2.78;
      95% confidence interval 1.21 - 6.4). There were no statistically significant
      differences in the mean estimated visual and mean calculated blood loss.
      CONCLUSIONS: The overall need for blood transfusion was significantly reduced by
      about two-thirds in women receiving the oxytocin + ergometrine combination.
      Consideration should be given to using oxytocin + ergometrine for prophylaxis of
      PPH at CS.

PMID- 27032859
TI  - Evaluating current knowledge of legislation and practice of obstetricians and
      gynaecologists in the management of fetal remains in South Africa.
AB  - BACKGROUND: In the clinical setting, the main legislative provisions governing
      the management and 'disposal' of fetal remains in South Africa are the Choice on
      Termination of Pregnancy Act 92 of 1996 and the Births and Deaths Registration
      Act 51 of 1992. OBJECTIVES: To determine obstetricians' and gynaecologists'
      current knowledge of this legislation. Current practice with regard to
      certification of death and methods of disposal of fetal material was also
      reviewed. METHODS: A questionnaire-based study was conducted. The data collected
      included demographic details, qualifications, years of experience, working
      environment (public/private practice), responses to general questions reviewing
      knowledge of current legislation, and practical experience. RESULTS: Seventy-six
      questionnaires were returned, with practitioners from the private and public
      sectors nearly equally represented. It was found that there is a concerning gap
      in obstetricians' and gynaecologists' knowledge of the law, and that some
      practitioners are acting outside the scope of the law. The study further revealed
      that patients' needs are not properly accommodated under the current legislative
      provisions, because the law prevents certain remains from being respectfully
      managed. Conclusions. The study findings suggest that improved training of
      practitioners, together with possible law reform, are required to better serve
      the needs of patients.

PMID- 27032860
TI  - Socioeconomic factors associated with asthma prevalence and severity among
      children living in low-income South African communities.
AB  - BACKGROUND: Rates of asthma, poverty and social deprivation are high among young
      people in South Africa (SA), yet asthma interventions largely remain focused on
      biomedical factors. OBJECTIVE: To investigate associations between socioeconomic
      factors and childhood asthma. METHODS: We recruited 6 002 children aged 10 - 17
      years from six low-income urban and rural sites in three SA provinces. Self
      report questionnaires measured health status, sociodemographics and socioeconomic
      factors. Logistic regression and mediation analyses were used to test models of
      risk factors for asthma prevalence and severity (frequency of attacks). RESULTS:
      Child anxiety (odds ratio (OR) 1.08; 95% confidence interval (CI) 1.04 - 1.12)
      and community violence (OR 1.14; 95% CI 1.00 - 1.30) were associated with
      increased odds of having asthma. Children doing more outdoor housework (OR 0.83;
      95% CI 0.71 - 0.98) and living in greater poverty (OR 0.93; 95% CI 0.88 - 0.99)
      had lower odds of having asthma. Severe asthma was predicted by child depression
      (OR 1.14; 95% CI 1.03 - 1.26) and greater household poverty (OR 1.14; 95% CI 1.01
      - 1.28). Most socioeconomic factors operated in 'risk pathways', wherein
      structural factors (e.g. urban living) were associated with individual factors
      (e.g. fewer outdoor tasks), which predicted greater odds of having asthma or
      severe exacerbations. CONCLUSIONS: This study suggests the need to consider the
      context of childhood asthma in SA for improved prevention and treatment. A
      multidisciplinary approach may be more effective than a biomedical model, given
      the plausible effects of psychosocial stress and poverty on asthma outcomes.

PMID- 27032864
TI  - Synthesis variants of quaternary ammonium polyethyleneimine nanoparticles and
      their antibacterial efficacy in dental materials.
AB  - BACKGROUND: Resin-based dental materials allow bacterial growth on their surface
      and lack antibacterial activity, leading to functional and esthetic failure.
      Quaternary ammonium polyethyleneimine (QPEI) nanoparticles (NPs) incorporated in
      resin-based composite at 2% wt/wt have demonstrated prolonged and complete
      inhibition of bacterial growth. This study focused on optimization of QPEI NP
      synthesis to reduce the concentration required for bacterial growth inhibition.
      The objective here was to enhance antimicrobial efficacy by excess base
      neutralization, using phosphoric or hydrochloric acid, and by using surfactants.
      METHODS: QPEI NP variants were prepared (i) under controlled neutralization of
      acid, using NaHCO3, (ii) under controlled carbonate ion neutralization with HCl
      or H3PO4 and (iii) by treatment with N-lauroylsarcosine or glycerol monostearate.
      NPs incorporated in the dental materials were examined for their antibacterial
      effect against Enterococcus faecalis. RESULTS: Controlled addition of NaHCO3
      resulted in modified QPEI NPs with an increased ability to inhibit bacterial
      growth. Surface treatment with N-lauroylsarcosine resulted in enhanced
      antibacterial activity at 0.5% wt/wt concentration in acrylate and epoxy resin
      based dental materials. CONCLUSIONS: The antimicrobial efficacy of QPEI NP may be
      improved significantly by controlling the addition of NaHCO3, neutralization of
      excess base and the surface-agent effect.

PMID- 27032865
TI  - Vertebroplasty and kyphoplasty for the treatment of thoracic fractures in
      osteoporotic patients: a finite element comparative analysis.
AB  - BACKGROUND: Vertebral compression fractures occur in the thoracolumbar junction,
      causing the collapse of the vertebral body. For their treatment, vertebroplasty
      and kyphoplasty are used, but it is still unknown which technique is to be
      preferred. METHODS: Finite element models of the thoracic spine were developed to
      evaluate the outcomes of vertebroplasty and kyphoplasty. A mild and severe
      collapse of T10 treated with vertebroplasty or kyphoplasty was studied. Stresses
      on the endplates and intradiscal pressures were extrapolated to determine the
      stress distribution in the adjacent structures. RESULTS: The validation ensured a
      correct stiffness and a proper kinematic of each functional spinal unit. The
      results demonstrated that a consolidation following vertebroplasty caused slight
      variations of intradiscal pressures and stresses. If a kyphoplasty was performed
      after a mild collapse of the vertebral body, a 25% stress reduction on endplates
      was found. In cases of severe collapse, when a partial height restoration was
      achieved, a 15% stress reduction was obtained, while with a full recovery of the
      anterior wall of the collapsed vertebra, there was a further reduction of 40%.
      CONCLUSIONS: To reduce the stresses on the adjacent endplates and the risk of
      fracture, the results suggest a kyphoplasty is to be preferred, trying to restore
      the initial vertebral body height.

PMID- 27032866
TI  - Acetazolamide polymorphism: a case of hybridization induced polymorphism?
AB  - The unusual phenomenon of the formation of the kinetic form as against the
      thermodynamic form upon slow cooling of boiling aqueous solution in the case of
      diuretic drug acetazolamide is rationalized in terms of "hybridization induced
      polymorphism" based on extensive experimental and theoretical investigations. 

PMID- 27032867
TI  - Morphological and molecular analyses of the spiruroid nematode, Falcaustra
      araxiana Massino, 1924 (= Spironoura araxiana) from the European pond turtle
      (Emys orbicularis).
AB  - There is little information on the phylogenetic position and life cycle of family
      Kathlaniidae. Falcaustra araxiana is a member of this family which infects the
      large intestine of the European pond turtle (Emys orbicularis). In the present
      study, morphological data and molecular analyses based on the 18S rDNA were
      performed on different types of F. araxiana originating from the large intestine
      and gastric nodules in the turtle. Morphological data revealed both larvae and
      adult stages in the gastric nodules. In addition, all nematodes recovered in the
      large intestine were adult worms. GenBank accession numbers KM200715 and KM200716
      were provided for adult F. araxiana located in the intestine and stomach,
      respectively, of E. orbicularis. The results of sequencing proved that these two
      types are completely similar. Accordingly, it can be hypothesized that nodule
      formation is a part of the life cycle of the parasite or a survival strategy.
      Furthermore, F. araxiana develops to the adult stage in the gastric mucosa prior
      to migrating to the large intestine. Phylogenetic analysis revealed that F.
      araxiana unexpectedly branched away from other members of the superfamily
      Seuratoidea (Truttaedacnitis truttae, Cucullanus robustus and C. baylisi) and
      showed a closer relationship with Paraquimperia africana, a member of the
      Ascaridoidea. It seems that phylogenetic reconstruction for the present parasite
      needs more detailed morphology, life cycle and molecular studies.

PMID- 27032869
TI  - Capillary Dielectric Barrier Discharge: Transition from Soft Ionization to
      Dissociative Plasma.
AB  - A capillary He dielectric barrier discharge was investigated with respect to its
      performance as a soft or dissociative ionization source. Spatiotemporal
      measurements of the plasma emission showed that in one voltage duty cycle the
      plasma evolved from a soft to dissociative ionization source. At the earliest
      time, the soft plasma was generated between the electrodes as well as outside the
      capillary forming the plasma jet. It was characterized by significant radiation
      arising only from He and N2(+), which are known to be important in the process of
      the soft ionization of the analyte. Later in time, the plasma capable of
      dissociating molecules develops. It is characterized by appreciable radiation
      from analyte dissociation products and is restricted to the interelectrode region
      in the capillary. Thus, for the soft ionization purposes, it is feasible to
      introduce the analyte exclusively in the plasma jet. For elemental analysis, the
      interelectrode plasma is appropriate.

PMID- 27032868
TI  - Access, treatment and outcomes of care: a study of ethnic minorities in Europe.
AB  - OBJECTIVES: Recent research has shown that ethnic minorities still have less
      access to medical care and are less satisfied with the treatment they receive and
      the outcomes of the health care process. This article assesses how migrants in
      Europe experience access, treatment and outcomes in the European health care
      systems. METHODS: Data were obtained from the QUALICOPC study (Quality and Costs
      of Primary Care in Europe). Regression analyses were used to estimate the access,
      treatment and outcomes of care for ethnic minorities. RESULTS: In several
      countries, migrants experience that the opening hours of their GP practice were
      too limited and indicate that the practice was too far away from their work or
      home (lower access). They are more likely to report negative patient-doctor
      communication and less continuity of care than native patients (worse treatment).
      In addition, they are less satisfied with the care they received and are more
      likely to postpone care (worse outcomes). CONCLUSIONS: In general, migrants are
      still disadvantaged during the health care process. However, our results also
      indicate that satisfaction with the health care process improves for second
      generation migrants in comparison with first-generation migrants.

PMID- 27032871
TI  - Vision for the Global Health and Cancer Section.

PMID- 27032870
TI  - Best Practices in Chronic Myeloid Leukemia Monitoring and Management.
AB  - : Optimal use of current therapeutic opportunities for chronic myeloid leukemia
      patients requires integration of clinical and laboratory monitoring. Assessment
      of molecular response (MR) by real-time quantitative polymerase chain reaction is
      the most sensitive way to monitor tyrosine kinase inhibitor (TKI) treatment
      efficacy. Besides major molecular response, which has emerged as a safe haven for
      survival since the initial studies of first-line imatinib treatment, two
      additional MR milestones have recently been defined: early molecular response and
      deep molecular response. The achievement of such MR milestones within defined
      time points during therapy is thought to draw the ideal trajectory toward optimal
      long-term outcome and, possibly, successful treatment discontinuation. Sensitive
      and reproducible MR measurement and proper interpretation of MR results are
      therefore critical to correctly inform therapeutic decisions. In patients who do
      not achieve an optimal response to TKI therapy, BCR-ABL1 mutation screening
      should also be performed, because it may deliver useful information for TKI
      choice. This review aims to help clinicians apply and translate the latest
      response definitions and clinical recommendations into practice. We provide a
      critical update on how these recommendations have incorporated MR levels in the
      clinical decision algorithms and how detection of BCR-ABL1 mutations should be
      interpreted. We also include a practical guide for pathologists and molecular
      biologists to best perform molecular testing and for hematologists and
      oncologists to best integrate it into routine practice. IMPLICATIONS FOR
      PRACTICE: Ever-more-potent therapeutic strategies have been developed for chronic
      myeloid leukemia (CML) in parallel with the evolution of therapeutic goals and
      the refinement of response definitions and monitoring schemes and procedures.
      Terminology and methodology continue to evolve rapidly, making it difficult for
      busy hematology/oncology professionals to keep abreast of the newest
      developments. Optimal CML patient management results from the timely and rational
      use of molecular testing, the critical assessment of the power and pitfalls of
      current technology, and the appropriate interpretation and contextualization of
      results.

PMID- 27032873
TI  - The Prognostic Significance of the Hedgehog Signaling Pathway in Colorectal
      Cancer.
AB  - Despite significant advances in the management of colorectal cancer (CRC) the
      identification of new prognostic biomarkers continues to be a challenge. Since
      its initial discovery, the role of the Hedgehog (Hh) signaling pathway in
      carcinogenesis has been extensively studied. We herein review and comment on the
      prognostic significance of the Hh signaling pathway in CRC. The differential
      expression of Hh pathway components between malignant and nonmalignant conditions
      as well as correlation of Hh activation markers with various clinicopathological
      parameters and the effect on disease-free survival, overall survival, and disease
      recurrence in patients with CRC is summarized and discussed. According to the
      studies reviewed herein the activation of the Hh pathway seems to be correlated
      with adverse clinicopathological features and worse survival. However, to date
      study results show significant variability with regard to the effect on outcomes.
      Such results need to be interpreted carefully and emphasize the need for further
      well designed studies to characterize the actual influence of the Hh pathway in
      CRC prognosis.

PMID- 27032872
TI  - Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor
      Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma
      Patients.
AB  - BACKGROUND: The use of gemcitabine as an adjuvant modality for cholangiocarcinoma
      (CC) is increasing, but limited data are available on predictive biomarkers of
      response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major
      transporter involved in gemcitabine intracellular uptake. This study investigated
      the putative predictive role of hENT-1 localization in tumor cells of CC patients
      undergoing treatment with adjuvant gemcitabine. METHODS: Seventy-one consecutive
      patients with resected CC receiving adjuvant gemcitabine at our center were
      retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor
      cells. The main outcome measure was disease-free survival (DFS). Hazard ratios
      (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from
      proportional hazards regression models stratified on quintiles of propensity
      score. RESULTS: Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%)
      were positive in the cytoplasm only, and 26 (36.6%) showed concomitant
      cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR
      0.49, 95% CI 0.24-0.99, p = .046) than those who were negative or positive only
      in the cytoplasm of tumor cells. Notably, the association between DFS and
      membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two
      cycles: HR 0.96, 95% CI 0.34-2.68; three to four cycles: HR 0.99, 95% CI 0.34
      2.90; five to six cycles: HR 0.27, 95% CI 0.10-0.77). CONCLUSION: hENT-1
      localization on tumor cell membrane may predict response to adjuvant gemcitabine
      in CC patients receiving more than four cycles of chemotherapy. Further
      prospective randomized trials on larger populations are required to confirm these
      preliminary results, so that optimal gemcitabine-based chemotherapy may be
      tailored for CC patients in the adjuvant setting. IMPLICATIONS FOR PRACTICE:
      Gemcitabine is becoming an increasingly used adjuvant modality in
      cholangiocarcinoma (CC), but limited data are available on predictive biomarkers
      of response. In this study, patients receiving more than four cycles of adjuvant
      gemcitabine and harboring Human equilibrative nucleoside transporter 1 (hENT-1,
      the major transporter involved in gemcitabine intracellular uptake) on tumor cell
      membrane had a longer disease-free survival compared with patients negative or
      positive for hENT-1 only in the cytoplasm of tumor cells. Overall these results
      may lay the basis for further prospective randomized trials based on a larger
      population of patients and may prove useful for tailoring appropriate gemcitabine
      based chemotherapy for CC patients in the adjuvant setting.

PMID- 27032874
TI  - Active recruitment and limited participant-load related to high participation in
      large population-based biobank studies.
AB  - OBJECTIVES: Insight into baseline participation rates and their determinants is
      crucial for designing future population-based biobank studies. We therefore
      conducted a systematic review and meta-analysis of baseline participation rates
      and their determinants in large longitudinal population-based biobank studies.
      STUDY DESIGN AND SETTING: We screened studies registered within the Public
      Population Project in Genomics and Society and in the Biobanking and Biomolecular
      Resources Research Infrastructure catalogues to find potentially eligible
      studies. We retrieved data with regard to participation rate, biobank design,
      performed measurements, and specific strategies for improving participation. We
      calculated weighted pooled proportions for each determinant using random-effects
      models. RESULTS: We included 25 studies (participation rates 5-96%).
      Participation rates were highest for studies involving face-to-face recruitment
      [82.6%; 95% confidence interval (CI): 72.2%, 90.9%], for studies in which
      participants were visited for an examination (77.5%; 95% CI: 64.0%, 88.6%) and
      for studies in which at maximum four measurements were performed (78.2%; 95% CI:
      69.7%, 85.7%). Specific strategies to improve participation were not found to be
      associated with higher participation rates. CONCLUSION: Specific choices of
      recruitment methods and design have consequences for participation rates. These
      insights may help to increase participation in future studies, thereby enhancing
      the validity of their findings.

PMID- 27032875
TI  - High quality of the evidence for medical and other health-related interventions
      was uncommon in Cochrane systematic reviews.
AB  - OBJECTIVES: To appraise the quality of evidence in systematic reviews (SRs)
      within the Cochrane Database of Systematic Reviews (CDSRs) across diverse topics
      and to explore the relationship between the strength of evidence using Grades of
      Recommendation, Assessment, Development, and Evaluation (GRADE) and the
      probability that authors would interpret that an intervention may be of value.
      STUDY DESIGN AND SETTING: We evaluated the SRs published on the CDSR from January
      1, 2013, to June 30, 2014. Two authors identified relevant SRs by independent
      searching of the Cochrane register. We further focused on SRs that incorporated
      tables with GRADE [summary of findings (SoF)]. Data were extracted independently
      by two authors. The quality of the evidence for the first listed primary outcome
      in SoF tables in each review and reasons for upgrade or downgrade were recorded.
      RESULTS: Overall, 1,394 SRs were identified. Of these, 608 (43.6%) incorporated
      GRADE. Within these reviews, only 13.5% (n = 82) reported a high quality and
      30.8% (n = 187) a moderate quality of evidence for the first listed primary
      outcome, whereas 31.7% (n = 193) had low level and 24% (n = 146) had very low
      level of evidence. High quality of evidence was more common in updated compared
      to new reviews and in pharmacologic than other types of interventions. Even when
      all outcomes listed in the SoFs were considered, only 116/608 (19.1%) of SRs had
      at least one outcome with high quality of evidence. Overall, only 4.1% (25/608)
      of SRs incorporating GRADE in SoF tables had high quality of evidence, allied
      both to significant results and a favorable interpretation of the intervention by
      the reviewers. CONCLUSION: Evidence of high quality is uncommon for medical and
      health-related interventions assessed with GRADE within the CDSR, and favorable
      evidence of high quality is even more uncommon.

PMID- 27032877
TI  - Kidney and aging - A narrative review.
AB  - The kidney undergoes age-related changes, reaching full functionality after the
      age of 5years and suffering a slow but progressive decline in its regulatory
      range of function (e.g. matching sodium and potassium excretion to dietary
      intake), starting at the age of ~20years, as well as in function (e.g. glomerular
      filtration) starting at a higher age. Age-related decline in renal function is
      also a matter of gender, race and genetic background. Pathogenetically, mediators
      of chronic inflammation, oxidative stress and the renin-angiotensin-aldosterone
      (RAAS) system are relevant factors determining renal aging, due to an enhanced
      incidence of cellular damage combined with reduced repair capacities. In addition
      cardiovascular diseases play a significant role. Features of renal aging include
      several functional alterations, like reduction of glomerular filtration rate,
      sodium reabsorption, potassium secretion, vitamin D3 synthesis, titratable acid
      excretion, responsiveness to hormones, and regulatory flexibility. Assessment of
      renal function has to account for age-related changes and is confronted with the
      challenge to differentiate between age-based physiological alterations and true
      pathological situations that require appropriate intervention.

PMID- 27032878
TI  - Editorial foreword special issue: "Angiogenesis-convergent or divergent, that is
      the question: Research toward targeted strategies in oncology".

PMID- 27032876
TI  - Effects of Silk Sericin on Incision Wound Healing in a Dorsal Skin Flap Wound
      Healing Rat Model.
AB  - BACKGROUND: The wound healing process is complex and still poorly understood.
      Sericin is a silk protein synthesized by silk worms (Bombyx mori). The objective
      of this study was to evaluate in vivo wound healing effects of a sericin
      containing gel formulation in an incision wound model in rats. MATERIAL/METHODS:
      Twenty-eight Wistar-Albino rats were divided into 4 groups (n=7). No intervention
      or treatment was applied to the Intact control group. For other groups, a dorsal
      skin flap (9*3 cm) was drawn and pulled up with sharp dissection. The Sham
      operated group received no treatment. The Placebo group received placebo gel
      without sericin applied to the incision area once a day from day 0 to day 9. The
      Sericin Group 3 received 1% sericin gel applied to the incision area once a day
      from day 0 to day 9. Hematoxylin and eosin stain was applied for histological
      analysis and Mallory-Azan staining was applied for histoimmunochemical analysis
      of antibodies and iNOS (inducible nitric oxide synthase), and desmin was applied
      to paraffin sections of skin wound specimens. Parameters of oxidative stress were
      measured in the wound area. RESULTS: Epidermal thickness and vascularization were
      increased, and hair root degeneration, edema, cellular infiltration, collagen
      discoloration, and necrosis were decreased in Sericin group in comparison to the
      Placebo group and the Sham operated group. Malonyldialdehyde (MDA) levels were
      decreased, but superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GPx) activities were increased in the sericin group. CONCLUSIONS: We
      found that sericin had significant positive effects on wound healing and
      antioxidant activity. Sericin-based formulations can improve healing of incision
      wounds.

PMID- 27032879
TI  - High prevalence of toxoplasmosis in free-range chicken of the Fernando de Noronha
      Archipelago, Brazil.
AB  - The present study aimed to determine the prevalence of toxoplasmosis in free
      range chickens of the Fernando de Noronha Archipelago, Brazil and to identify
      risk factors associated with Toxoplasma gondii infection. Blood samples were
      collected from all the adult chickens raised in the Archipelago and screened by
      Indirect Fluorescent Antibody Test (430 samples, in total). Univariate analysis
      (Chi-square) and logistic regression were used to investigate the relationship
      between various variables possibly predictive of an increased likelihood of T.
      gondii infection. The overall prevalence of T. gondii infection in chickens of
      the Fernando de Noronha Archipelago was 88.4% (380/430; 84.6%-91.0%; 95% CI),
      ranging from 57.1% to 100.0% among the studied properties. The risk factors
      associated with T. gondii infection were the number of domestic cats in the
      properties (p=0.022), the presence of feral cats (p=0.006) and the presence of an
      open water source (p=0.046). Domestic and feral cats should be prevented from
      accessing the water and food supplied to chickens. 

PMID- 27032880
TI  - Are we considering the QTc interval of our patients?

PMID- 27032881
TI  - Coexistence of cutaneous phosphaturic mesenchymal tumour and postoperative
      hypoparathyroidism.

PMID- 27032882
TI  - Dual device cannulation of an intradiverticular minor papilla.

PMID- 27032883
TI  - Surveillance of guideline practices for duodenoscope and linear echoendoscope
      reprocessing in a large healthcare system.
AB  - BACKGROUND AND AIMS: To assess the adequacy of currently recommended duodenoscope
      and linear echoendoscope (DLE) automatic endoscope reprocessing (AER) and high
      level disinfection (HLD), we collected daily post-reprocessing surveillance
      cultures of 106 DLEs in 21 Providence and Affiliate Hospitals. METHODS: Daily
      qualitative surveillance of dried, post-HLD DLEs was conducted for a minimum of
      30 days at each facility. Positivity rates for any microbial growth and growth of
      high-concern pathogens were reported. Potential effects of DLE manufacturer, age,
      and AER processor on culture-positivity rate were assessed. RESULTS: Microbial
      growth was recovered from 201 of 4032 specimens (5%) or 189 of 2238 encounters
      (8.4%), including 23 specimens (.6%) or 21 encounters (.9%) for a high-concern
      pathogen. Wide variations in culture-positivity rate were observed across
      facilities. No striking difference in culture-positivity rate was seen among 8
      DLE models, 3 DLE manufacturers, DLE age, manual or bedside cleanser, or
      automatic flushing system use. However, there was suggestive evidence that Custom
      Ultrasonics AER (Warminster, Pa, USA) had a lower culture-positivity rate than
      Medivators AER (Cantel Medical Corp., Little Falls, NJ, USA) for high-concern
      pathogen growth (0/1079 vs 21/2735 specimens or 0/547 vs 20/1582 encounters). Two
      endoscopes grew intestinal flora on several occasions despite multiple HLD. No
      multidrug-resistant organism was detected. CONCLUSIONS: In this multicenter DLE
      surveillance study, microbial growth was recovered in 5.0% of specimens (8.4% of
      encounters), with most being environmental microbes. Enteric bacterial flora was
      recovered in .6% of specimens (.9% of encounters), despite compliance with 2014
      U.S. guidelines and manufacturers' recommendations for cleaning and HLD process.
      The observed better performance of Custom Ultrasonics AER deserves further
      investigation.

PMID- 27032884
TI  - Prevention of esophageal strictures after endoscopic submucosal dissection with
      the injection of botulinum toxin type A.
AB  - BACKGROUND AND AIMS: The use of endoscopic submucosal dissection (ESD) for
      management of widespread superficial esophageal squamous carcinoma is closely
      associated with esophageal stenosis. We investigated the efficacy and feasibility
      of endoscopic injection of botulinum toxin type A (BTX-A) for preventing
      esophageal strictures after ESD for superficial esophageal squamous carcinoma.
      METHODS: Sixty-seven patients with superficial esophageal squamous cell
      carcinomas with mucosal defects that exceeded one half of the circumference of
      the esophagus after ESD treatment were enrolled and randomly divided into 2
      groups (group A, n = 33; group B, n = 34). Patients in group A (BTX-A group) were
      immediately injected with BTX-A after ESD, whereas patients in group B (control
      group) received ESD only. Endoscopy was performed when patients reported
      dysphagia symptoms and at 12 weeks post-ESD in patients without symptoms.
      Patients who experienced post-ESD esophageal strictures in both groups received
      bougie dilation. RESULTS: The number of patients who experienced esophageal
      strictures in group A (per protocol analysis, 6.1%, 2/33; intention to treat
      analysis, 11.4%, 4/35) was significantly less than that seen in group B (per
      protocol analysis, 32.4%, 11/34; intention to treat analysis, 37.8%, 14/37) (P <
      .05). Moreover, the number of bougie dilation procedures was significantly lower
      in group A (mean, 1.5; range, 0-2) than in group B (mean, 2.8; range, 0-5) (P <
      .05). CONCLUSIONS: Endoscopic injection of BTX-A was effective in preventing post
      ESD esophageal strictures and decreasing the times of bougie dilation procedures.
      ( CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-12003188.).

PMID- 27032885
TI  - Studies on the influence of CCK-8 on the ability of obestatin to reduce food
      intake, gain in body weight and related lipid parameters.
AB  - In an effort to mimic in part the redundancy of satiety peptides involved in
      energy homeostasis, the combined benefits of the well-established satiety peptide
      CCK8 and an apparently anorectic peptide obestatin were studied in Swiss albino
      mice. The optimal dose of obestatin that was required to give the most pronounced
      effect with CCK8 was worked out by varying the concentration of obestatin while
      keeping CCK8 concentration constant at 200 nmol/KgBW. Mice administered 160 nmol
      obestatin and 200 nmol CCK8 per kilogram body weight showed the most drastic
      reduction in food intake. Gain in body weight was arrested after day four during
      the eight day experiment. These studies reemphasize the beneficial effects
      imparted by co-administration of obestatin and CCK8 and their potential use
      towards countering obesity. 

PMID- 27032886
TI  - Early Change in Urine Protein as a Surrogate End Point in Studies of IgA
      Nephropathy: An Individual-Patient Meta-analysis.
AB  - BACKGROUND: The role of change in proteinuria as a surrogate end point for
      randomized trials in immunoglobulin A nephropathy (IgAN) has previously not been
      thoroughly evaluated. STUDY DESIGN: Individual patient-level meta-analysis.
      SETTING & POPULATION: Individual-patient data for 830 patients from 11 randomized
      trials evaluating 4 intervention types (renin-angiotensin system [RAS] blockade,
      fish oil, immunosuppression, and steroids) examining associations between changes
      in urine protein and clinical end points at the individual and trial levels.
      SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of IgAN with
      measurements of proteinuria at baseline and a median of 9 (range, 5-12) months
      follow-up, with at least 1 further year of follow-up for the clinical outcome.
      PREDICTOR: 9-month change in proteinuria. OUTCOME: Doubling of serum creatinine
      level, end-stage renal disease, or death. RESULTS: Early decline in proteinuria
      at 9 months was associated with lower risk for the clinical outcome (HR per 50%
      reduction in proteinuria, 0.40; 95% CI, 0.32-0.48) and was consistent across
      studies. Proportions of treatment effect on the clinical outcome explained by
      early decline in proteinuria were estimated at 11% (95% CI, -19% to 41%) for RAS
      blockade and 29% (95% CI, 6% to 53%) for steroid therapy. The direction of the
      pooled treatment effect on early change in proteinuria was in accord with the
      direction of the treatment effect on the clinical outcome for steroids and RAS
      blockade. Trial-level analyses estimated that the slope for the regression line
      for the association of treatment effects on the clinical end points and for the
      treatment effect on proteinuria was 2.15 (95% Bayesian credible interval, 0.10
      4.32). LIMITATIONS: Study population restricted to 11 trials, all having fewer
      than 200 patients each with a limited number of clinical events. CONCLUSIONS:
      Results of this analysis offer novel evidence supporting the use of an early
      reduction in proteinuria as a surrogate end point for clinical end points in IgAN
      in selected settings.

PMID- 27032887
TI  - Pharmacological Provocation of Outflow-Tract Tachycardia in a Patient With
      Brugada Syndrome.
AB  - We present a case of a symptomatic patient with Brugada syndrome, who had
      sustained right ventricular outflow tract tachycardia after pronounced exercise
      induced ST segment elevation in V1 and V2. In electrophysiological study he
      developed right ventricular outflow tract tachycardia provoked by combined
      infusion of ajmaline and orciprenaline. After ablation no further arrhythmia was
      provoked by pharmacological stimulation.

PMID- 27032888
TI  - Beyond Stenosis With Fractional Flow Reserve Via Computed Tomography and Advanced
      Plaque Analyses for the Diagnosis of Lesion-Specific Ischemia.
AB  - In the treatment of stable coronary artery disease (CAD), the determination of
      stenosis severity by invasive coronary angiography (ICA) is a critical procedure,
      and for borderline lesions, the detection of ischemia through invasive fractional
      flow reserve (FFR) is the gold standard. With advances in computational fluid
      dynamics, FFR can now be calculated noninvasively using anatomic data from
      coronary computed tomographic angiography (CCTA). This technique is known as
      FFRCT. The purpose of this review is to summarize the science of FFRCT, describe
      its diagnostic accuracy, discuss its clinical and economic impact, and elucidate
      factors beyond stenosis severity that may mechanistically relate to lesion
      specific ischemia. These factors include adverse atherosclerotic plaque
      characteristics such as positive remodelling, low-attenuation plaque, and spotty
      calcification, as well as aggregate plaque volume. These factors can be
      appreciated noninvasively by CCTA but not by ICA. The diagnostic accuracy of
      FFRCT, compared with the gold standard of FFR, has been validated in 3
      prospective multicentre blinded core laboratory-controlled trials, and as a
      result FFRCT has been approved by the US Food and Drug Administration for
      clinical use. FFRCT has also been shown in a clinical utility trial to better
      identify patients without obstructive CAD when compared with standard noninvasive
      assessment of stable CAD, thereby avoiding unnecessary angiograms. In addition,
      the use of FFRCT has been shown to allow for a significant cost savings compared
      with traditional care. It is therefore important for cardiologists to appreciate
      the value of this important new methodology.

PMID- 27032889
TI  - Reply to Letter From Kroll et al.-Risk of Death With Conducted Energy Weapons.

PMID- 27032891
TI  - Synthesis and evaluation of 6-(3-[(18)F]fluoro-2-hydroxypropyl)-substituted 2
      pyridylbenzothiophenes and 2-pyridylbenzothiazoles as potential PET tracers for
      imaging Abeta plaques.
AB  - 3-[(18)F]Fluoro-2-hydroxypropyl substituted compounds were synthesized and
      evaluated as novel (18)F-labeled PET tracers for imaging Abeta plaque in a living
      brain. All compounds exhibited high binding affinities toward the synthetic
      Abeta1-42 aggregate and/or Alzheimer's disease brain homogenate. In the microPET
      study with normal mice, the 3-[(18)F]fluoro-2-hydroxypropyl substituted compounds
      resulted in fast brain washout by reducing the lipophilicities of the compounds.
      Intriguingly, (S)-configured PET tracers, (S)-[(18)F]1b and (S)-[(18)F]1c,
      exhibited a 2.8 and 4.0-fold faster brain washout rate at a peak/30 min in the
      mouse brain than the corresponding (R)-configured PET tracers despite there being
      no meaningful difference in binding affinities toward Abeta plaque. A further
      evaluation of (S)-[(18)F]1c with healthy rhesus monkeys also revealed excellent
      clearance from the frontal cortex with ratios of 7.0, 16.0, 30.0 and 49.0 at a
      peak/30, 60, 90, and 120 min, respectively. These results suggest that (S)
      [(18)F]1c may be a potential PET tracer for imaging Abeta plaque in a living
      brain.

PMID- 27032890
TI  - Tetrahydroprotoberberine alkaloids with dopamine and sigma receptor affinity.
AB  - Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (+/-)
      stepholidine that (a) contain various alkoxy substituents at the C10 position
      and, (b) were de-rigidified with respect to (+/-)-stepholidine, were synthesized
      and evaluated for affinity at dopamine and sigma receptors in order to evaluate
      effects on D3 and sigma2 receptor affinity and selectivity. Small n-alkoxy groups
      are best tolerated by D3 and sigma2 receptors. Among all compounds tested, C10
      methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest
      affinity for sigma2 receptors as well as sigma2 versus sigma1 selectivity and
      also showed the highest D3 receptor affinity. De-rigidification of stepholidine
      resulted in decreased affinity at all receptors evaluated; thus the tetracyclic
      THPB framework is advantageous for affinity at dopamine and sigma receptors.
      Docking of the C10 analogues at the D3 receptor, suggest that an ionic
      interaction between the protonated nitrogen atom and Asp110, a H-bond interaction
      between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and
      Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and
      Phe345, are critical for high affinity of the compounds. 

PMID- 27032892
TI  - Role of Ragulator in the Regulation of Mechanistic Target of Rapamycin Signaling
      in Podocytes and Glomerular Function.
AB  - Aberrant activation of mechanistic target of rapamycin complex 1 (mTORC1) in
      glomerular podocytes leads to glomerular insufficiency and may contribute to the
      development of glomerular diseases, including diabetic nephropathy. Thus, an
      approach for preventing mTORC1 activation may allow circumvention of the onset
      and progression of mTORC1-dependent podocyte injury and glomerular diseases.
      mTORC1 activation requires inputs from both growth factors and nutrients that
      inactivate the tuberous sclerosis complex (TSC), a key suppressor of mTORC1, on
      the lysosome. Previous studies in mice revealed that the growth factor
      phosphatidylinositol 3-kinase pathway and mTORC1 are essential for maintaining
      normal podocyte function, suggesting that direct inhibition of the
      phosphatidylinositol 3-kinase pathway or mTORC1 may not be an ideal approach to
      sustaining physiologic podocyte functions under certain disease conditions. Here,
      we report the role of the Ragulator complex, which recruits mTORC1 to lysosomes
      in response to nutrient availability in podocytes. Notably, podocytes lacking
      Ragulator maintain basal mTORC1 activity. Unlike podocyte-specific mTORC1
      knockout mice, mice lacking functional Ragulator in podocytes did not show
      abnormalities in podocyte or glomerular function. However, aberrant mTORC1
      activation induced by active Rheb in podocyte-specific TSC1-knockout (podo-TSC1
      KO) mice did require Ragulator. Moreover, ablation of Ragulator in the podocytes
      of podo-TSC1 KO mice or streptozotocin-induced diabetic mice significantly
      blocked the development of pathologic renal phenotypes. These observations
      suggest that the blockade of mTORC1 recruitment to lysosomes may be a useful
      clinical approach to attenuate aberrant mTORC1 activation under certain disease
      conditions.

PMID- 27032893
TI  - Residual Host Cell Protein Promotes Polysorbate 20 Degradation in a Sulfatase
      Drug Product Leading to Free Fatty Acid Particles.
AB  - This study investigated the root cause behind an observed free fatty acid
      particle formation and resulting Polysorbate 20 (PS20) loss for a sulfatase drug
      product upon long-term storage at 5 +/- 3 degrees C. Reversed- phase
      chromatography with mass spectrometric analysis as well as charged aerosol
      detection was used to characterize the peaks associated with the intact and
      degraded PS20. Additionally, a proteomics study was undertaken to identify the
      residual host cell proteins in the sulfatase drug substance. PS20 stability
      studies were conducted in the presence of sulfatase, a sulfatase inhibitor,
      putative phospholipase B-like 2, and mock drug substance produced using a null
      cell line vector under experimental conditions optimized for PS20 degradation.
      This study provides the first published evidence where the residual host cell
      protein present in the drug substance was identified and experimentally shown to
      catalyze the breakdown of PS20 in a protein formulation over time, resulting in
      free fatty acid particles and PS20 loss. This study demonstrates the importance
      of early detection of potential impurities in the protein drug substance that may
      contribute to polysorbate degradation to make a judicious selection of the
      surfactant and its optimized concentration for the final drug product.

PMID- 27032894
TI  - Protein crystallization screens developed at the MRC Laboratory of Molecular
      Biology.
AB  - In order to solve increasingly challenging protein structures with
      crystallography, crystallization reagents and screen formulations are regularly
      investigated. Here, we briefly describe 96-condition screens developed at the MRC
      Laboratory of Molecular Biology: the LMB sparse matrix screen, Pi incomplete
      factorial screens, the MORPHEUS grid screens and the ANGSTROM optimization
      screen. In this short review, we also discuss the difficulties and advantages
      associated with the development of protein crystallization screens.

PMID- 27032895
TI  - Chronic hepatitis B infection and risk of antituberculosis drug-induced liver
      injury: Systematic review and meta-analysis.
AB  - BACKGROUND: Antituberculosis drug-induced liver injury (ATDILI) is a major safety
      concern for the treatment of tuberculosis (TB). The impact of chronic hepatitis B
      infection (CHBI) on the risk of ATDILI is still controversial. In this study, we
      aimed to assess systematically the influence of CHBI on the susceptibility to
      ATDILI. METHODS: We reviewed all English-language medical literature with the
      medical subject search headings hepatitis B and antitubercular agents from the
      major medical databases. Thereafter, a systematic review and meta-analysis was
      performed on those publications that qualified. RESULTS: A total of 938 citations
      were retrieved on the initial major database search, from which 15 studies were
      determined to be eligible for analysis. While undergoing anti-TB treatment, 575
      cases with drug-induced liver injury (DILI) and 4128 controls without DILI were
      enrolled into this analysis. The pooled odds ratio of all studies for the CHBI to
      ATDILI was 2.18 (95% confidence interval, 1.41-3.37). Among the studies with a
      strict definition of DILI (alanine aminotransferase > 5 * upper limit of normal
      value) and combination anti-TB regimen, the impact of CHBI on ATDILI was
      significant only in the prospective studies (odds ratio, 3.41; 95% confidence
      interval, 1.77-6.59), but not in the case-control studies. However, in the
      studies with a strict definition of DILI and isoniazid only treatment, the
      association between CHBI and ATDILI was not statistically significant.
      CONCLUSION: This meta-analysis suggests that CHBI may increase the risk of ATDILI
      in the standard combination therapy for active TB. Close follow-up and regular
      liver test monitoring are mandatory to treat TB in chronic hepatitis B carriers.

PMID- 27032896
TI  - Metric sex estimation from the postcranial skeleton for the Colombian population.
AB  - This research explores the best univariate and multivariate indicators for sex
      estimation using 51 standard osteometric measurements of all six major
      postcranial long bones, bones of the shoulder girdle, pelvic girdle, and the
      calcaneus from a modern, Colombian skeletal collection. The hypotheses being
      tested are (1) that postcrania will yield accurate sex classification rates and
      (2) the shoulder girdle will demonstrate the highest discrimination, based on
      results from previous research. The sample consists of 134 individuals (50
      females, 84 males) between the ages of 19 and 93 with a mean age of 47 years. The
      sample is from the Colombian Skeletal Collection, consisting of skeletons from
      cemeteries in Bogota, with recent years of death. The methods include univariate
      and multivariate discriminant function analysis (DFA). The results for this
      sample indicate the same general pattern of univariate classification
      effectiveness as found in research on North Americans; however, here the humerus
      performs better than the distal femur and proximal tibia as demonstrated in some
      North American samples. The cross-validated percent correct univariate
      classification for the postcranial elements ranges from 64.8% to 86.1% (p<0.05).
      The highest univariate classification rates were for the scapular height (86.1%)
      and the humeral head diameter (86.0%). The highest multivariate classification
      rates are with the scapula (93.5%), os coxa (92.0%), clavicle (89.9%), humerus
      (89.1%), and ulna (89.1%). This study provides sectioning points to easily
      estimate sex using Colombian population-specific formulae. This research aids in
      forensic individuation, as the long bones of the postcranial elements are
      relatively resistant to taphonomic processes. Furthermore, the ability to achieve
      such a high degree of success from a single bone is preferable for the fast-paced
      forensic anthropology laboratories in Colombia that process hundreds to thousands
      of cases each year. This research plays an important role in the development of
      population standards in Colombia and South America and provides a robust method
      that can withstand courtroom scrutiny. 

PMID- 27032897
TI  - Klippel-Feil syndrome with butterfly vertebrae: rare case.

PMID- 27032898
TI  - A comparison of two methods to evaluate a narrow spinal canal: routine magnetic
      resonance imaging versus three-dimensional reconstruction.
AB  - BACKGROUND CONTEXT: In routine clinical practice, the presence of lumbar spinal
      stenosis (LSS) is assessed on axial magnetic resonance images (MRI) typically
      acquired using a preselected spine sagittal angle. Given the natural lordosis of
      the lumbar spine, not all axial slices will be parallel to the disc and
      perpendicular to the spinal canal and, thus, are not optimal for the assessment
      of dural sac cross-sectional area (DCSA). PURPOSE: The objective of this study
      was to compare DCSA measurements from routinely acquired clinical images with
      three-dimensional (3D)-reconstructed images. STUDY DESIGN: This is a cross
      sectional study. PATIENT SAMPLE: The sample consists of 390 patients referred for
      lumbar imaging with some aspect of anatomical LSS found, with no prior back
      surgery, 40 years of age or older, and with available volumetric MR images to
      allow 3D reconstruction of the spine. OUTCOME MEASURES: The outcome of interest
      in this study was dural sac cross sectional area. METHODS: Spine images were 3D
      reconstructed at the level of the disc, perpendicular to the spinal canal. Dural
      sac cross-sectional area was measured for both 3D-reconstructed and routinely
      acquired clinical images using the slice orientation captured. RESULTS: Dural sac
      cross-sectional area for the lower lumbar levels (L4-L5 and L5-S1) was
      significantly different between routinely acquired clinical images and 3D
      reconstructed images, with a standard error of measurement of 12.98 and 19.73
      mm(2), respectively. CONCLUSIONS: When canal size is of interest, particularly
      when LSS affecting the lower lumbar levels is of concern, 3D reconstruction of
      clinical images should be considered.

PMID- 27032899
TI  - Chronic endurance exercise training offsets the age-related attenuation in
      contraction-induced rapid vasodilation.
AB  - Aging is associated with attenuated contraction-induced rapid onset vasodilation
      (ROV). We sought to examine whether chronic exercise training would improve ROV
      in older adults. Additionally, we examined whether a relationship between
      cardiorespiratory fitness and ROV exists in young and older adults. Chronically
      exercise-trained older adults (n = 16; 66 +/- 2 yr, mean +/- SE) performed single
      muscle contractions in the forearm and leg at various intensities. Brachial and
      femoral artery diameter and blood velocity were measured using Doppler
      ultrasound. Vascular conductance (VC) was calculated as the quotient of blood
      flow (ml/min) and mean arterial pressure (mmHg). These data were compared with
      our previously published work from an identical protocol in 16 older untrained
      (66 +/- 1 yr, mean +/- SE) and 14 young (23 +/- 1 yr) adults. Peak (DeltaVCpeak)
      and total vasodilator (VCtotal) responses were greater in trained compared with
      untrained older adults across leg exercise intensities (P < 0.05). There were no
      differences in responses between trained older and young adults in the arm or leg
      at any exercise intensity (P > 0.05). Comparison of DeltaVCpeak in a subset of
      subjects at an absolute workload in the leg revealed that trained older adults
      exhibited augmented responses relative to untrained older adults. Exercise
      capacity (Vo2 peak) was associated with DeltaVCpeak and VCtotal across arm (r =
      0.59-0.64) and leg exercise intensities (r = 0.55-0.68, P < 0.05) in older
      adults. Our data demonstrate that 1) chronic exercise training improves ROV in
      the arm and leg of trained older adults, such that age-related differences in ROV
      are abolished, and 2) VO2peak is associated with DeltaVCpeak responses in both
      limbs of older adults. 

PMID- 27032900
TI  - Transcutaneous electrical acupoint stimulation alleviates adverse cardiac
      remodeling induced by overload training in rats.
AB  - Electroacupuncture has been shown previously to alleviate cardiac ischemia
      reperfusion injury. Overload training (OT) exercise can result in profound
      cardiac damage and remodeling. In this study, we aimed to examine whether
      transcutaneous electrical acupoint stimulation (TEAS), a novel noninvasive and
      low-risk alternative to electroacupuncture, could counteract short-term OT
      induced cardiac remodeling, fibrosis, autophagy, and apoptosis. Sixty rats were
      randomly divided into eight groups (n = 7 or 8/group): control, regular exercise,
      OT, OT plus low-, moderate- or high-frequency TEAS preconditioning, OT plus
      moderate-frequency TEAS postconditioning, or transcutaneous electrical
      nonacupoint stimulation (TENAS) preconditioning. The cardiac weight index (heart
      weight/body weight) was determined. Left ventricular morphology was examined by
      hematoxylin and eosin staining. Cardiac fibrosis and apoptosis were determined by
      Masson's trichrome and TUNEL staining, respectively. The presence of
      autophagosomes was observed by transmission electron microcopy. The expressions
      of autophagic markers (LC3 II/I and Beclin-1) were determined by Western blot.
      The results showed that 1) OT induced adverse cardiac structure changes but did
      not affect the cardiac weight index; 2) OT increased cardiac fibrosis and
      apoptosis and induced autophagosome formation with upregulated LC3 II/I and
      Beclin-1 expression; 3) TEAS preconditioning effectively alleviated OT-induced
      cardiac structure changes, fibrosis, apoptosis, and autophagy; 4) TEAS
      preconditioning produced better protective effects than TEAS postconditioning or
      TENAS preconditioning. Our results demonstrate that TEAS preconditioning protects
      the heart from OT-induced cardiac injury/remodeling, probably by inhibition of
      fibrosis, autophagy, and apoptosis. 

PMID- 27032902
TI  - Short-term aerobic exercise training improves gut peptide regulation in
      nonalcoholic fatty liver disease.
AB  - Obesity-related nonalcoholic fatty liver disease (NAFLD) is now the most common
      chronic liver disease. Exercise and diet are uniformly prescribed treatments for
      NAFLD; however, there are limited empirical data on the effects of exercise
      training on metabolic function in these patients. The purpose of this study was
      to investigate the fasting and glucose-stimulated adaptation of gut peptides to
      short-term aerobic exercise training in patients with NAFLD. Twenty-two obese
      subjects, 16 with NAFLD [body mass index (BMI), 33.2 +/- 1.1 (SE) kg/m(2)] and 6
      obese controls (BMI, 31.3 +/- 1.2 kg/m(2)), were enrolled in a supervised aerobic
      exercise program (60 min/day, 85% of their heart rate maximum, for 7 days).
      Fasting and glucose-stimulated glucagon-like peptide-1 (GLP-17-36) and peptide
      tyrosine tyrosine (PYYTotal) concentrations in plasma were assessed before and
      after the exercise program. Initially, the NAFLD group had higher fasting PYY
      (NAFLD = 117 +/- 18.6, control = 47.2 +/- 6.4 pg/ml, P < 0.05) and GLP-1 (NAFLD =
      12.4 +/- 2.2, control = 6.2 +/- 0.2 pg/ml, P < 0.05) and did not significantly
      increase GLP-1 or PYY in response to glucose ingestion. After the exercise
      program, fasting GLP-1 was reduced in the NAFLD group (10.7 +/- 2.0 pg/ml, P <
      0.05). Furthermore, exercise training led to significant increase in the acute (0
      30 min) PYY and GLP-1 responses to glucose in the NAFLD group, while the total
      area under the glucose-stimulated GLP-1 response curve was reduced in both NAFLD
      and controls (P < 0.05). In summary, 7 days of vigorous aerobic exercise
      normalized the dynamic PYY and GLP-1 responses to nutrient stimulation and
      reduced the GLP-1 response in NAFLD, suggesting that exercise positively
      modulates gut hormone regulation in obese adults with NAFLD.

PMID- 27032903
TI  - Effects of intramuscular administration of 1alpha,25(OH)2D3 during skeletal
      muscle regeneration on regenerative capacity, muscular fibrosis, and
      angiogenesis.
AB  - The recent discovery of the vitamin D receptor (VDR) in regenerating muscle
      raises the question regarding the action of vitamin D3 on skeletal muscle
      regeneration. To investigate the action of vitamin D3 on this process, the
      tibialis anterior muscle of male C57BL/6 mice (10 wk of age) was injected with
      1.2% BaCl2 to induce extensive muscle injury. The bioactive form of vitamin D3
      [1alpha,25(OH)2D3] was administered daily via intramuscular injections during the
      regenerative phase (days 4-7 postinjury). Physiological and supraphysiological
      doses of 1alpha,25(OH)2D3 relative to 1 MUg/kg muscle wet weight and mouse body
      weight were investigated. Muscle samples were collected on day 8 postinjury to
      examine proteins related to vitamin D3 metabolism (VDR, CYP24A1, and CYP27B1),
      satellite cell differentiation and regenerative muscle fiber formation [myogenin
      and embryonic myosin heavy chain (EbMHC)], protein synthesis signaling (Akt, p70
      S6K1, 4E-BP1, and myostatin), fiber-type composition (fast and slow MHCs),
      fibrous formation (vimentin), and angiogenesis (CD31). Administration of
      1alpha,25(OH)2D3 at physiological and supraphysiological doses enhanced VDR
      expression in regenerative muscle. Moreover, CYP24A1 and vimentin expression was
      increased, accompanying decreased myogenin and EbMHC expression at the
      supraphysiological dose. However, there was no change in CYP27B1, Akt, p70 S6K1,
      4E-BP1, myostatin, fast and slow MHCs, or CD31 expression at any dose
      investigated. Taken together, administration of 1alpha,25(OH)2D3 at a
      supraphysiological dose decreased satellite cell differentiation, delayed
      regenerative muscle fiber formation, and increased muscular fibrosis. However,
      protein synthesis signaling, fiber-type composition, and angiogenesis were not
      affected by either 1alpha,25(OH)2D3 administration at a physiological or
      supraphysiological dose.

PMID- 27032901
TI  - Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to
      insulin sensitivity and respond to acute exercise in humans.
AB  - Several recent reports indicate that the balance of skeletal muscle
      phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant
      of muscle contractile function and metabolism. The purpose of this study was to
      determine relationships between skeletal muscle PC, PE and insulin sensitivity,
      and whether PC and PE are dynamically regulated in response to acute exercise in
      humans. Insulin sensitivity was measured via intravenous glucose tolerance in
      sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n =
      15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle
      biopsies were obtained at rest, immediately after 90 min of cycle ergometry at
      50% maximal oxygen consumption (Vo2 max), and 2-h postexercise (recovery).
      Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass
      spectrometry analysis. ATH had greater levels of muscle PC and PE compared with
      OB and T2D (P < 0.05), with total PC and PE positively relating to insulin
      sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D
      compared with OB and ATH (P < 0.05), tended to be elevated in OB vs. ATH (P =
      0.07), and was inversely related to insulin sensitivity among the entire cohort
      (r = -0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly
      after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE
      ratio remained unchanged in all groups. In summary, total muscle PC and PE are
      positively related to insulin sensitivity while PC:PE ratio is inversely related
      to insulin sensitivity in humans. A single session of exercise significantly
      alters skeletal muscle PC and PE levels, but not PC:PE ratio. 

PMID- 27032904
TI  - Vervets and macaques: Similarities and differences in their responses to l-BMAA.

PMID- 27032905
TI  - Influences of rapid pacing-induced electrical remodeling on pharmacological
      manipulation of the atrial refractoriness in rabbits.
AB  - Electrical remodeling plays a pivotal role in maintaining the reentry during
      atrial fibrillation. In this study, we assessed influence of electrical
      remodeling on pharmacological manipulation of the atrial refractoriness in
      rabbits. We used an atrial electrical remodeling model of the rabbit, subjected
      to rapid atrial pacing (RAP; 600 beats/min) for 2-4 weeks, leading to shortening
      of atrial effective refractory period (AERP). Intravenous administration of dl
      sotalol (6 mg/kg), bepridil (1 mg/kg), amiodarone (10 mg/kg) or vernakalant (3
      mg/kg) significantly prolonged the AERP both in the control and RAP rabbits. The
      extents in the RAP rabbits were similar to those in the control animals. On the
      other hand, prolonging effects of intravenously administered ranolazine (10
      mg/kg) or tertiapin-Q (0.03 mg/kg) on the AERP in the RAP rabbits were more
      potent than those in the control animals. These results suggest that rapid pacing
      induced electrical remodeling effectively modified the prolonging effects of
      ranolazine and tertiapin-Q on the AERP in contrast to those of clinically
      available antiarrhythmic drugs, dl-sotalol, bepridil amiodarone and vernakalant. 

PMID- 27032906
TI  - Trichosanthin-induced autophagy in gastric cancer cell MKN-45 is dependent on
      reactive oxygen species (ROS) and NF-kappaB/p53 pathway.
AB  - Trichosanthin (TCS), isolated from the root tuber of Trichosanthes kirilowii
      tubers in the Cucurbitaceae family, owns a great deal of biological and
      pharmacological activities including anti-virus and anti-tumor. TCS has been
      reported to induce cell apoptosis of a diversity of cancers, including cervical
      cancer, choriocarcinoma, and gastric cancer, etc. However, whether TCS would
      induce autophagy in gastric cancer cells was seldom investigated. In current
      study, human gastric cancer MKN-45 cell growth was significantly inhibited by
      TCS. The anti-proliferation effect of TCS was due to an increased autophagy,
      which was confirmed by monodansylcadervarine (MDC) staining, up-regulation of
      Autophagy protein 5 (Atg5), and conversion of LC3 I to LC3 II (autophagosome
      marker). In addition, TCS induced reactive oxygen species (ROS) in MKN-45 cells
      and ROS scavenger N-acetylcysteine (NAC) significantly reversed TCS-induced
      autophagy. Furthermore, NF-kappaB/p53 pathway was activated during the process of
      autophagy induced by TCS and the ROS generation was mediated by it in MKN-45
      cells. In vivo results showed that TCS exerted significantly anti-tumor effect on
      MKN-45 bearing mice. Considering the clinical usage of TCS on other human
      diseases, these research progresses provided a new insight into cancer research
      and new therapeutic avenues for patients with gastric cancer. 

PMID- 27032907
TI  - Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian
      cancer cells.
AB  - Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta
      prostrata, have been reported to possess various biological activities such as
      anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the
      cytotoxicity of the triterpenoids in human cancer cells and their molecular
      mechanism of action are poorly understood. In the present study, we found that
      eclalbasaponin II with one glucose moiety has potent cytotoxicity in three
      ovarian cancer cells and two endometrial cancer cells compared to an aglycone
      echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II
      treatment dose-dependently increased sub G1 population. Annexin V staining
      revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian
      cancer cells. In addition, eclalbasaponin II-induced cell death was associated
      with characteristics of autophagy; an increase in acidic vesicular organelle
      content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor
      BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin
      II activated JNK and p38 signaling and inhibited the mTOR signaling. We further
      demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator
      attenuated the eclalbasaponin II-induced autophagy. This suggests that
      eclalbasaponin II induces apoptotic and autophagic cell death through the
      regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

PMID- 27032908
TI  - The prostaglandin E2/EP4 receptor/cyclic AMP/T-type Ca(2+) channel pathway
      mediates neuritogenesis in sensory neuron-like ND7/23 cells.
AB  - We investigated mechanisms for the neuritogenesis caused by prostaglandin E2
      (PGE2) or intracellular cyclic AMP (cAMP) in sensory neuron-like ND7/23 cells.
      PGE2 caused neuritogenesis, an effect abolished by an EP4 receptor antagonist or
      inhibitors of adenylyl cyclase (AC) or protein kinase A (PKA) and mimicked by the
      AC activator forskolin, dibutyryl cAMP (db-cAMP), and selective activators of PKA
      or Epac. ND7/23 cells expressed both Cav3.1 and Cav3.2 T-type Ca(2+) channels (T
      channels). The neuritogenesis induced by db-cAMP or PGE2 was abolished by T
      channel blockers. T-channels were functionally upregulated by db-cAMP. The
      PGE2/EP4/cAMP/T-channel pathway thus appears to mediate neuritogenesis in sensory
      neurons. 

PMID- 27032909
TI  - Neuroprotective effect of S-allyl-l-cysteine derivatives against endoplasmic
      reticulum stress-induced cytotoxicity is independent of calpain inhibition.
AB  - S-allyl-l-cysteine (SAC) is known to have neuroprotective properties. We
      synthesized various SAC derivatives and tested their effects on endoplasmic
      reticulum stress-induced neurotoxicity in cultured hippocampal neurons (HPNs).
      Among the compounds tested, S-propyl-l-cysteine (SPC) exhibited the strongest
      neuroprotective activity in HPNs, followed by S-ethyl-l-cysteine (SEC) and S
      methyl-l-cysteine (SMC). Unlike SAC and SMC, SPC and SEC did not have inhibitory
      activity on MU-calpain, suggesting that the mechanism underlying the protective
      activity of SPC and SEC differs from that of SAC. 

PMID- 27032910
TI  - The effects of castration followed testosterone supplementation in prostatic
      complex of Artibeus planirostris (Chiroptera: Phyllostomidae).
AB  - The prostatic complex (ventral and dorsal regions) of Artibeus planirostris
      exhibits seasonal variations throughout the year. Circulating testosterone was
      correlated with prostate weight, showing an increase from autumn to summer, with
      the highest peak in summer corresponding to the largest breeding season. This
      indicates that the level of serum testosterone influences variations in both
      testicular and prostatic weights. Serum testosterone levels seem to be closely
      related to the different responses of these glands throughout the year. The
      castration (consequent suppression of testosterone) and subsequent hormone
      supplementation may elucidate the relationship of these two glandular types with
      testosterone. Thus, the aim of this study was to evaluate the effect of
      castration and the testosterone supplementation in the male prostatic complex of
      A. planirostris. The results indicated that both prostatic regions were affected
      by the ablation of testosterone, presenting a decrease in cell proliferation and
      an increase in apoptosis. Similarly, the prostate was responsive to hormonal
      supplementation, having a recovery of the active morphophysiological pattern with
      testosterone supplementation. However, data have shown that the ventral region
      was more sensitive to changes in testosterone than the dorsal, presenting greater
      cell renewal. 

PMID- 27032912
TI  - Editorial: Neurosurgical Focus: first among equals in online, freely accessible
      journals.

PMID- 27032913
TI  - Cervical spine surgery in professional athletes: a systematic review.
AB  - Cervical surgery is one of the most common surgical spinal procedures performed
      around the world. The authors performed a systematic review of the literature
      reporting the outcomes of cervical spine surgery in high-level athletes in order
      to better understand the nuances of cervical spine pathology in this population.
      A search of the MEDLINE database using the search terms "cervical spine" AND
      "surgery" AND "athletes" yielded 54 abstracts. After exclusion of publications
      that did not meet the criteria for inclusion, a total of 8 papers reporting the
      outcome of cervical spine surgery in professional or elite athletes treated for
      symptoms secondary to cervical spine pathology (focusing in degenerative
      conditions) remained for analysis. Five of these involved the management of
      cervical disc herniation, 3 were specifically about traumatic neurapraxia. The
      majority of the patients included in this review were American football players.
      Anterior cervical discectomy and fusion (ACDF) was commonly performed in high
      level athletes for the treatment of cervical disc herniation. Most of the studies
      suggested that return to play is safe for athletes who are asymptomatic after
      ACDF for cervical radiculopathy due to disc herniation. Surgical treatment may
      provide a higher rate of return to play for these athletes than nonsurgical
      treatment. Return to play after cervical spinal cord contusion may be possible in
      asymptomatic patients. Cervical cord signal changes on MRI may not be an absolute
      contraindication for return to play in neurologically intact patients, according
      to some authors. Cervical contusions secondary to cervical stenosis may be
      associated with a worse outcome and a higher recurrence rate than those those
      secondary to disc herniation. The evidence is low (Level IV) and individualized
      treatment must be recommended. 

PMID- 27032914
TI  - Craniofacial injuries in professional cricket: no more a red herring.
AB  - The issue of head injury in a noncontact sport like cricket is a matter of great
      debate and it carries more questions than answers. Recent incidents of fatal head
      injuries in individuals wearing a helmet have caused some to question the
      protective value of the helmet. The authors discuss the pattern, type of injury,
      incidents, and location of cranio-facio-ocular injuries in professional cricket
      to date. They evaluate the history of usage of the helmet in cricket, changes in
      design, and the protective value, and they compare the efficacy of various
      sports' helmets with injury profiles similar to those in cricket. The drop test
      and air cannon test are compared for impact energy attenuation performance of
      cricket helmets. A total of 36 cases of head injuries were identified, of which 5
      (14%) were fatal and 9 (22%) were career-terminating events. Batsmen are the most
      vulnerable to injury, bearing 86% of the burden, followed by wicketkeepers (8%)
      and fielders (5.5%). In 53% of cases, the ball directly hit the head, while in
      19.5% of cases the ball entered the gap between the peak and the faceguard.
      Ocular injuries to 3 wicketkeepers proved to be career-terminating injuries. The
      air cannon test is a better test for evaluating cricket helmets than the drop
      test. Craniofacial injuries are more common than popularly believed. There is an
      urgent need to improve the efficacy and compliance of protective restraints in
      cricket. A strict injury surveillance system with universal acceptance is needed
      to identify the burden of injuries and modes for their prevention. 

PMID- 27032915
TI  - Rugby headgear and concussion prevention: misconceptions could increase
      aggressive play.
AB  - OBJECTIVE Multiple studies have illustrated that rugby headgear offers no
      statistically significant protection against concussions. However, there remains
      concern that many players believe rugby headgear in fact does prevent
      concussions. Further investigation was undertaken to illustrate that
      misconceptions about concussion prevention and rugby headgear may lead to an
      increase in aggressive play. METHODS Data were constructed by Internet survey
      solicitation among United States collegiate rugby players across 19 teams.
      Initial information given was related to club, age, experience, use of headgear,
      playing time, whether the rugger played football or wrestling in high school, and
      whether the player believed headgear prevented concussion. Data were then
      constructed as to whether wearing headgear would increase aggressive playing
      style secondary to a false sense of protection. RESULTS A total of 122 players
      responded. All players were male. The average player was 19.5 years old and had
      2.7 years of experience. Twenty-three of 122 players (18.9%) wore protective
      headgear; 55.4% of players listed forward as their primary position. Overall,
      45.8% (55/120) of players played 70-80 minutes per game, 44.6% (54/121) played
      football or wrestled in high school, 38.1% (45/118) believed headgear prevented
      concussions, and 42.2% (51/121) stated that if they were using headgear they
      would be more aggressive with their play in terms of running or tackling.
      Regression analysis illustrated that those who believed headgear prevented
      concussions were or would be more likely to engage in aggressive play (p =
      0.001). CONCLUSIONS Nearly 40% of collegiate rugby players surveyed believed
      headgear helped to prevent concussions despite no scientific evidence that it
      does. This misconception about rugby headgear could increase aggressive play.
      Those who believed headgear prevented concussion were, on average, 4 times more
      likely to play with increased aggressive form than those who believed headgear
      did not prevent concussions (p = 0.001). This can place all players at increased
      risk without providing additional protection. Further investigation is warranted
      to determine if headgear increases the actual measured incidence of concussion
      among rugby players in the United States. 

PMID- 27032916
TI  - Predictors of postconcussion syndrome in collegiate student-athletes.
AB  - OBJECTIVE Sport-related concussion (SRC) has emerged as a public health problem,
      especially among student-athletes. Whereas most concussions resolve by 2 weeks, a
      minority of patients experience postconcussion syndrome (PCS), in which symptoms
      persist for months. The objective of this study was to elucidate factors
      predictive of PCS among a sample of National Collegiate Athletic Association
      (NCAA) student-athletes in the academic years 2009-2010 to 2014-2015. METHODS The
      SRC data originated from the NCAA Injury Surveillance Program (ISP) in the 2009
      2010 to 2014-2015 academic seasons. The NCAA ISP is a prospective database made
      up of a convenience sample of schools across all divisions. All SRCs are reported
      by certified athletic trainers. The PCS group consisted of concussed student
      athletes with concussion-related symptoms that lasted >= 4 weeks. The non-PCS
      group consisted of concussed student-athletes with symptom resolution in <= 2
      weeks. Those with symptoms that resolved in the intermediate area of 2-4 weeks
      were excluded. Odds ratios (ORs) were estimated using logistic regression.
      RESULTS During the 2009-2010 to 2014-2015 seasons, 1507 NCAA student-athletes
      sustained an SRC, 112 (7.4%) of whom developed PCS (i.e., concussion-related
      symptoms that lasted >= 4 weeks). Men's ice hockey contributed the largest
      proportion of concussions to the PCS group (28.6%), whereas men's football
      contributed the largest proportion of concussions in the non-PCS group (38.6%).
      In multivariate analysis, recurrent concussion was associated with increased odds
      of PCS (OR 2.08, 95% CI 1.28-3.36). Concussion symptoms that were also associated
      with increased odds of PCS included retrograde amnesia (OR 2.75, 95% CI 1.34
      5.64), difficulty concentrating (OR 2.35, 95% CI 1.23-4.50), sensitivity to light
      (OR 1.97, 95% CI 1.09-3.57), and insomnia (OR 2.19, 95% CI 1.30-3.68). Contact
      level, sex, and loss of consciousness were not associated with PCS. CONCLUSIONS
      Postconcussion syndrome represents one of the most impactful sequelae of SRC. In
      this study of exclusively collegiate student-athletes, the authors found that
      recurrent concussions and various concussion-related symptoms were associated
      with PCS. The identification of initial risk factors for the development of PCS
      may assist sports medicine clinicians in providing timely interventions and
      treatments to prevent morbidity and shorten recovery time after SRC. 

PMID- 27032917
TI  - Sports-related brain injuries: connecting pathology to diagnosis.
AB  - Brain injuries are becoming increasingly common in athletes and represent an
      important diagnostic challenge. Early detection and management of brain injuries
      in sports are of utmost importance in preventing chronic neurological and
      psychiatric decline. These types of injuries incurred during sports are referred
      to as mild traumatic brain injuries, which represent a heterogeneous spectrum of
      disease. The most dramatic manifestation of chronic mild traumatic brain injuries
      is termed chronic traumatic encephalopathy, which is associated with profound
      neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be
      diagnosed by postmortem examination, new diagnostic methodologies are needed for
      early detection and amelioration of disease burden. This review examines the
      pathology driving changes in athletes participating in high-impact sports and how
      this understanding can lead to innovations in neuroimaging and biomarker
      discovery. 

PMID- 27032918
TI  - The science and questions surrounding chronic traumatic encephalopathy.
AB  - Recently, the pathobiology, causes, associated factors, incidence and prevalence,
      and natural history of chronic traumatic encephalopathy (CTE) have been debated.
      Data from retrospective case series and high-profile media reports have fueled
      public fear and affected the medical community's understanding of the role of
      sports-related traumatic brain injury (TBI) in the development of CTE. There are
      a number of limitations posed by the current evidence that can lead to confusion
      within the public and scientific community. In this paper, the authors address
      common questions surrounding the science of CTE and propose future research
      directions. 

PMID- 27032919
TI  - Introduction: Sports injuries: diagnosis and management strategies.

PMID- 27032920
TI  - Pediatric sports-related traumatic brain injury in United States trauma centers.
AB  - OBJECTIVE Traumatic brain injury (TBI) in children is a significant public health
      concern estimated to result in over 500,000 emergency department (ED) visits and
      more than 60,000 hospitalizations in the United States annually. Sports
      activities are one important mechanism leading to pediatric TBI. In this study,
      the authors characterize the demographics of sports-related TBI in the pediatric
      population and identify predictors of prolonged hospitalization and of increased
      morbidity and mortality rates. METHODS Utilizing the National Sample Program of
      the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports
      related TBI data from children (age 0-17 years) across 5 sports categories: fall
      or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian
      sports, and aquatic sports. Multivariable regression analysis was used to
      identify predictors of prolonged length of stay (LOS) in the hospital or
      intensive care unit (ICU), medical complications, inpatient mortality rates, and
      hospital discharge disposition. Statistical significance was assessed at alpha <
      0.05, and the Bonferroni correction (set at significance threshold p = 0.01) for
      multiple comparisons was applied in each outcome analysis. RESULTS From 2003 to
      2012, in total 3046 pediatric sports-related TBIs were recorded in the NTDB, and
      these injuries represented 11,614 incidents nationally after sample weighting.
      Fall or interpersonal contact events were the greatest contributors to sports
      related TBI (47.4%). Mild TBI represented 87.1% of the injuries overall. Mean (+/
      SEM) LOSs in the hospital and ICU were 2.68 +/- 0.07 days and 2.73 +/- 0.12
      days, respectively. The overall mortality rate was 0.8%, and the prevalence of
      medical complications was 2.1% across all patients. Severities of head and
      extracranial injuries were significant predictors of prolonged hospital and ICU
      LOSs, medical complications, failure to discharge to home, and death. Hypotension
      on admission to the ED was a significant predictor of failure to discharge to
      home (OR 0.05, 95% CI 0.03-0.07, p < 0.001). Traumatic brain injury incurred
      during roller sports was independently associated with prolonged hospital LOS
      compared with FIC events (mean increase 0.54 +/- 0.15 days, p < 0.001).
      CONCLUSIONS In pediatric sports-related TBI, the severities of head and
      extracranial traumas are important predictors of patients developing acute
      medical complications, prolonged hospital and ICU LOSs, in-hospital mortality
      rates, and failure to discharge to home. Acute hypotension after a TBI event
      decreases the probability of successful discharge to home. Increasing TBI
      awareness and use of head-protective gear, particularly in high-velocity sports
      in older age groups, is necessary to prevent pediatric sports-related TBI or to
      improve outcomes after a TBI. 

PMID- 27032921
TI  - Adult sports-related traumatic brain injury in United States trauma centers.
AB  - OBJECTIVE Sports-related traumatic brain injury (TBI) is an important public
      health concern estimated to affect 300,000 to 3.8 million people annually in the
      United States. Although injuries to professional athletes dominate the media,
      this group represents only a small proportion of the overall population. Here,
      the authors characterize the demographics of sports-related TBI in adults from a
      community-based trauma population and identify predictors of prolonged
      hospitalization and increased morbidity and mortality rates. METHODS Utilizing
      the National Sample Program of the National Trauma Data Bank (NTDB), the authors
      retrospectively analyzed sports-related TBI data from adults (age >= 18 years)
      across 5 sporting categories-fall or interpersonal contact (FIC), roller sports,
      skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable
      regression analysis was used to identify predictors of prolonged hospital length
      of stay (LOS), medical complications, inpatient mortality rates, and hospital
      discharge disposition. Statistical significance was assessed at alpha < 0.05, and
      the Bonferroni correction for multiple comparisons was applied for each outcome
      analysis. RESULTS From 2003 to 2012, in total, 4788 adult sports-related TBIs
      were documented in the NTDB, which represented 18,310 incidents nationally.
      Equestrian sports were the greatest contributors to sports-related TBI (45.2%).
      Mild TBI represented nearly 86% of injuries overall. Mean (+/- SEM) LOSs in the
      hospital or intensive care unit (ICU) were 4.25 +/- 0.09 days and 1.60 +/- 0.06
      days, respectively. The mortality rate was 3.0% across all patients, but was
      statistically higher in TBI from roller sports (4.1%) and aquatic sports (7.7%).
      Age, hypotension on admission to the emergency department (ED), and the severity
      of head and extracranial injuries were statistically significant predictors of
      prolonged hospital and ICU LOSs, medical complications, failure to discharge to
      home, and death. Traumatic brain injury during aquatic sports was similarly
      associated with prolonged ICU and hospital LOSs, medical complications, and
      failure to be discharged to home. CONCLUSIONS Age, hypotension on ED admission,
      severity of head and extracranial injuries, and sports mechanism of injury are
      important prognostic variables in adult sports-related TBI. Increasing TBI
      awareness and helmet use-particularly in equestrian and roller sports-are
      critical elements for decreasing sports-related TBI events in adults. 

PMID- 27032922
TI  - Sports-related concussions: diagnosis, complications, and current management
      strategies.
AB  - Sports-related concussions (SRCs) are traumatic events that affect up to 3.8
      million athletes per year. The initial diagnosis and management is often
      instituted on the field of play by coaches, athletic trainers, and team
      physicians. SRCs are usually transient episodes of neurological dysfunction
      following a traumatic impact, with most symptoms resolving in 7-10 days; however,
      a small percentage of patients will suffer protracted symptoms for years after
      the event and may develop chronic neurodegenerative disease. Rarely, SRCs are
      associated with complications, such as skull fractures, epidural or subdural
      hematomas, and edema requiring neurosurgical evaluation. Current standards of
      care are based on a paradigm of rest and gradual return to play, with decisions
      driven by subjective and objective information gleaned from a detailed history
      and physical examination. Advanced imaging techniques such as functional MRI, and
      detailed understanding of the complex pathophysiological process underlying SRCs
      and how they affect the athletes acutely and long-term, may change the way
      physicians treat athletes who suffer a concussion. It is hoped that these
      advances will allow a more accurate assessment of when an athlete is truly safe
      to return to play, decreasing the risk of secondary impact injuries, and provide
      avenues for therapeutic strategies targeting the complex biochemical cascade that
      results from a traumatic injury to the brain. 

PMID- 27032923
TI  - The Sport Concussion Assessment Tool: a systematic review.
AB  - OBJECTIVE Over the last 2 decades, sport-related concussion (SRC) has garnered
      significant attention. Even with increased awareness and athlete education,
      sideline recognition and real-time diagnosis remain crucial. The need for an
      objective and standardized assessment of concussion led to the eventual
      development of the Sport Concussion Assessment Tool (SCAT) during the Second
      International Conference on Concussion in Sport in 2004, which is now in its
      third iteration (SCAT3). In an effort to update our understanding of the most
      well-known sideline concussion assessment, the authors conducted a systematic
      review of the SCAT and the evidence supporting its use to date. METHODS English
      language titles and abstracts published between 1995 and October 2015 were
      searched systematically across 4 electronic databases and a review was conducted
      in accordance with the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines adapted for the review of a heterogeneous collection
      of study designs. Peer-reviewed journal articles were included if they reported
      quantitative data on any iteration of the SCAT, Standardized Assessment of
      Concussion (SAC), or modified Balance Error Scoring System (mBESS) data at
      baseline or following concussion in an exclusively athlete population with any
      portion older than 13 years of age. Studies that included nonathletes, only
      children less than 13 years old, exclusively BESS data, exclusively symptom scale
      data, or a non-SCAT-related assessment were excluded. RESULTS The database search
      process yielded 549 abstracts, and 105 full-text articles were reviewed with 36
      meeting criteria for inclusion. Nineteen studies were associated with the SAC, 1
      was associated with the mBESS exclusively, and 16 studies were associated with a
      full iteration of the SCAT. The majority of these studies (56%) were prospective
      cohort studies. Male football players were the most common athletes studied. An
      analysis of the studies focused on baseline differences associated with age, sex,
      concussion history, and the ability to detect an SRC. CONCLUSIONS Looking toward
      the upcoming Concussion in Sport Group meeting in fall 2016, one may expect
      further revision to the SCAT3. However, based on this systematic review, the
      authors propose further, in-depth study of an already comprehensive concussion
      test, with acute, diagnostic, as well as long-term use. 

PMID- 27032924
TI  - Clinical evaluation of concussion: the evolving role of oculomotor assessments.
AB  - Sports-related concussion is a change in brain function following a direct or an
      indirect force to the head, identified in awake individuals and accounting for a
      considerable proportion of mild traumatic brain injury. Although the neurological
      signs and symptoms of concussion can be subtle and transient, there can be
      persistent sequelae, such as impaired attention and balance, that make affected
      patients particularly vulnerable to further injury. Currently, there is no
      accepted definition or diagnostic criteria for concussion, and there is no single
      assessment that is accepted as capable of identifying all patients with
      concussion. In this paper, the authors review the available screening tools for
      concussion, with particular emphasis on the role of visual function testing. In
      particular, they discuss the oculomotor assessment tools that are being
      investigated in the setting of concussion screening. 

PMID- 27032925
TI  - Retirement-from-sport considerations following pediatric sports-related
      concussion: case illustrations and institutional approach.
AB  - The decision to advise an athlete to retire from sports following sports-related
      concussion (SRC) remains a persistent challenge for physicians. In the absence of
      strong empirical evidence to support recommendations, clinical decision making
      must be individualized and should involve a multidisciplinary team of experts in
      concussion and traumatic brain injury. Although previous authors have advocated
      for a more conservative approach to these issues in child and adolescent
      athletes, there are few reports outlining considerations for this process among
      this unique population. Here, the authors use multiple case illustrations to
      discuss 3 subgroups of clinical considerations for sports retirement among
      pediatric SRC patients including the following: those with structural brain
      abnormalities identified on neuroimaging, those presenting with focal
      neurological deficits and abnormalities on physical examination, and those in
      whom the cumulative or prolonged effects of concussion are suspected or
      demonstrated. The authors' evolving multidisciplinary institutional approach to
      return-to-play and retirement decision making in pediatric SRC is also presented.

PMID- 27032926
TI  - Sport-related structural brain injury associated with arachnoid cysts: a
      systematic review and quantitative analysis.
AB  - OBJECTIVE Arachnoid cysts (ACs) are congenital lesions bordered by an arachnoid
      membrane. Researchers have postulated that individuals with an AC demonstrate a
      higher rate of structural brain injury after trauma. Given the potential
      neurological consequences of a structural brain injury requiring neurosurgical
      intervention, the authors sought to perform a systematic review of sport-related
      structural-brain injury associated with ACs with a corresponding quantitative
      analysis. METHODS Titles and abstracts were searched systematically across the
      following databases: PubMed, Embase, CINAHL, and PsycINFO. The review was
      conducted in accordance with the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) statement. Peer-reviewed case reports, case series, or
      observational studies that reported a structural brain injury due to a sport or
      recreational activity (hereafter referred to as sport-related) with an associated
      AC were included. Patients were excluded if they did not have an AC, suffered a
      concussion without structural brain injury, or sustained the injury during a non
      sport-related activity (e.g., fall, motor vehicle collision). Descriptive
      statistical analysis and time to presentation data were summarized. Univariate
      logistic regression models to assess predictors of neurological deficit, open
      craniotomy, and cystoperitoneal shunt were completed. RESULTS After an initial
      search of 994 original articles, 52 studies were found that reported 65 cases of
      sport-related structural brain injury associated with an AC. The median age at
      presentation was 16 years (range 4-75 years). Headache was the most common
      presenting symptom (98%), followed by nausea and vomiting in 49%. Thirteen
      patients (21%) presented with a neurological deficit, most commonly hemiparesis.
      Open craniotomy was the most common form of treatment (49%). Bur holes and cyst
      fenestration were performed in 29 (45%) and 31 (48%) patients, respectively.
      Seven patients (11%) received a cystoperitoneal shunt. Four cases reported
      medical management only without any surgical intervention. No significant
      predictors were found for neurological deficit or open craniotomy. In the
      univariate model predicting the need for a cystoperitoneal shunt, the odds of
      receiving a shunt decreased as age increased (p = 0.004, OR 0.62 [95% CI 0.45
      0.86]) and with male sex (p = 0.036, OR 0.15 [95% CI 0.03-0.88]). CONCLUSIONS
      This systematic review yielded 65 cases of sport-related structural brain injury
      associated with ACs. The majority of patients presented with chronic symptoms,
      and recovery was reported generally to be good. Although the review is subject to
      publication bias, the authors do not find at present that there is
      contraindication for patients with an AC to participate in sports, although
      parents and children should be counseled appropriately. Further studies are
      necessary to better evaluate AC characteristics that could pose a higher risk of
      adverse events after trauma. 

PMID- 27032927
TI  - Characterizing the Zika Virus Genome - A Bioinformatics Study.
AB  - BACKGROUND: The recent epidemic of Zika virus infections in South and Latin
      America have raised serious concern on its ramifications for the population in
      the Americas and spread of the virus worldwide. The Zika virus disease is a
      relatively new phenomenon for which sufficient and comprehensive data and
      investigative reports have not been available to date. OBJECTIVE: To carry out a
      bioinformatics study of the available Zika virus genomic sequences to
      characterize the virus. METHOD: 2D graphical representation method is used for
      visual rendering and compute sequence parameters and descriptors of the African
      and Asian-American groups of the Zika viruses to characterize the sequences. We
      also used MEGA5.2 and other software to compute various biological properties of
      interest like phylogenetic relationships, transition-transversion ratios, amino
      acid usage, codon usage bias and hydropathy index of the Zika genomes and
      virions. RESULTS: The phylogenetic relationships show that the African and Asian
      American Zika virus genomes are grouped in two clades. The 2D plots of typical
      genomes of these types also show dramatic differences indicating that the gene
      sequences at the 5'-end coding regions for the structural proteins are rather
      strongly conserved. Among other characteristics, the transition/transversion
      ratio matrices for the sequences in each of the two clades show that analogous to
      the dengue virus, the transition rates are about 10 to 15 times the transversion
      rates. CONCLUSION: These findings are important for computer-assisted approaches
      towards surveillance of emerging Zika virus strains as well as in the design of
      drugs and vaccines to combat the growth and spread of the Zika virus.

PMID- 27032928
TI  - Expansion of CRISPR targeting sites in Bombyx mori.
AB  - The CRISPR/Cas9 system has been proven as a revolutionary genome engineering
      tool. In most cases, single guide RNA (sgRNA) targeting sites have been designed
      as GN19NGG or GGN18NGG, because of restriction of the initiation nucleotide for
      RNA Pol III promoters. Here, we demonstrate that the U6 promoter from a
      lepidopteran model insect, Bombyx mori, effectively expressed the sgRNA initiated
      with any nucleotide bases (adenine, thymine, guanine or cytosine), which further
      expands the CRISPR targeting space. A detailed expansion index in the genome was
      analysed when N20NGG was set as the CRISPR targeting site instead of GN19NGG, and
      revealed a significant increase of suitable targets, with the highest increase
      occurring on the Z sex chromosome. Transfection of different types of N20NGG
      sgRNAs targeting the enhanced green fluorescent protein (EGFP) combined with
      Cas9, significantly reduced EGFP expression in the BmN cells. An endogenous gene,
      BmBLOS2, was also disrupted by using various types of N20NGG sgRNAs, and the
      cleavage efficiency of N20NGG sgRNAs with different initial nucleotides and GC
      contents was evaluated in vitro. Furthermore, transgenic silkworms expressing
      Cas9 and sgRNAs targeting the BmBLOS2 gene were generated with many types of
      mutagenesis. The typical transparent skin phenotype in knock-out silkworms was
      stable and inheritable, suggesting that N20NGG sgRNAs function sufficiently in
      vivo. Our findings represent a renewal of CRISPR/Cas9 target design and will
      greatly facilitate insect functional genetics research. 

PMID- 27032929
TI  - CXCL6 promotes human hepatocyte proliferation through the CXCR1-NFkappaB pathway
      and inhibits collagen I secretion by hepatic stellate cells.
AB  - Hepatocyte proliferation and collagen I (COLI) secretion are important processes
      during liver regeneration. This study aimed to investigate the role of CXCL6 in
      hepatocyte proliferation and COLI secretion. Serum CXCL6 levels in patients with
      chronic hepatitis B (CHB) were examined and the effects of CXCL6 on the
      proliferation of L02 hepatocytes and the secretion of COLI from LX2 human hepatic
      stellate cells were evaluated. We found that serum CXCL6 levels increased
      gradually with disease progression of CHB, and there was positive correlation
      between serum CXCL6 level and alanine transaminase (ALT) and aspartate
      transaminase (AST). In vitro, CXCL6 promoted L02 proliferation but this was
      blocked upon CXCR1 knockdown. The level of phospho-IkappaBalpha was upregulated
      by CXCL6 but downregulated by CXCR1 siRNA in L02 cells. CXCL6 inhibited the
      secretion of COLI by LX2 cells, dependent on CXCR1 and CXCR2. Taken together,
      these data suggest that increased expression of CXCL6 during CHB could promote
      hepatocyte proliferation through the CXCR1-NFkappaB pathway and inhibit the
      secretion of COLI by hepatic stellate cells.

PMID- 27032930
TI  - Impact of depressive symptoms and hepatic encephalopathy on health-related
      quality of life in cirrhotic hepatitis C patients.
AB  - Depression, common in chronic medical conditions, and hepatic encephalopathy
      (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are
      associated with impaired health-related quality of life (HRQOL) in cirrhosis and
      hepatitis C (HCV). This study investigated the impact of depression and HE on
      HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory
      patients, with varying degrees of cirrhosis secondary to HCV, was prospectively
      enrolled in this study. Participants were assessed for any current depressive,
      fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation
      to determine the presence of HE symptoms. Participants reported current HRQOL on
      general health and liver disease-specific questionnaires. Diagnosis and current
      health status were confirmed via medical records. The associations between
      disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were
      measured. Predictors of HRQOL in this sample were determined. Depressive symptoms
      (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively
      experiencing both conditions at the time of study participation. A significant
      positive association was found between depressive symptoms and HE severity (P =
      .05). Depressive symptoms were significantly associated with fatigue (P < .001),
      daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific
      HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general
      HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and
      HE were significant predictors of reduced HRQOL (P < .001), with depressive
      symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE
      accounted for 68.0 % of the variance. Findings suggest a possible
      pathophysiological link between depression and HE in cirrhosis, and potentially a
      wider-reaching benefit of treating minimal and overt HE than previously
      appreciated.

PMID- 27032931
TI  - Optimal training dataset composition for SVM-based, age-independent, automated
      epileptic seizure detection.
AB  - Automated seizure detection is a valuable asset to health professionals, which
      makes adequate treatment possible in order to minimize brain damage. Most
      research focuses on two separate aspects of automated seizure detection: EEG
      feature computation and classification methods. Little research has been
      published regarding optimal training dataset composition for patient-independent
      seizure detection. This paper evaluates the performance of classifiers trained on
      different datasets in order to determine the optimal dataset for use in
      classifier training for automated, age-independent, seizure detection. Three
      datasets are used to train a support vector machine (SVM) classifier: (1) EEG
      from neonatal patients, (2) EEG from adult patients and (3) EEG from both
      neonates and adults. To correct for baseline EEG feature differences among
      patients feature, normalization is essential. Usually dedicated detection systems
      are developed for either neonatal or adult patients. Normalization might allow
      for the development of a single seizure detection system for patients
      irrespective of their age. Two classifier versions are trained on all three
      datasets: one with feature normalization and one without. This gives us six
      different classifiers to evaluate using both the neonatal and adults test sets.
      As a performance measure, the area under the receiver operating characteristics
      curve (AUC) is used. With application of FBC, it resulted in performance values
      of 0.90 and 0.93 for neonatal and adult seizure detection, respectively. For
      neonatal seizure detection, the classifier trained on EEG from adult patients
      performed significantly worse compared to both the classifier trained on EEG data
      from neonatal patients and the classier trained on both neonatal and adult EEG
      data. For adult seizure detection, optimal performance was achieved by either the
      classifier trained on adult EEG data or the classifier trained on both neonatal
      and adult EEG data. Our results show that age-independent seizure detection is
      possible by training one classifier on EEG data from both neonatal and adult
      patients. Furthermore, our results indicate that for accurate age-independent
      seizure detection, it is important that EEG data from each age category are used
      for classifier training. This is particularly important for neonatal seizure
      detection. Our results underline the under-appreciated importance of training
      dataset composition with respect to accurate age-independent seizure detection. 

PMID- 27032932
TI  - Biomechanical performance of retrograde nail for supracondylar fractures
      stabilization.
AB  - The study compared the biomechanical performance of retrograde nail used to
      stabilize supracondylar fracture (three different levels) by means of finite
      element analysis. Three different nail lengths (200, 260, and 300 mm) of
      stainless steel and titanium nails were under consideration. Intact femur model
      was reconstructed from Digital Imaging and Communications in Medicine images of
      Thai cadaveric femur scanned by computed tomography spiral scanner, whereas
      geometry of retrograde nail was reconstructed with the data obtained from three
      dimensional laser scanner. The retrograde nail was virtually attached to the
      femur before nodes and elements were generated for finite element model. The
      finite element models were analyzed in two stages, the early stage of fracture
      healing and the stage after fracture healing. The finding indicated that
      purchasing proximal locking screw in the bowing region of the femur may be at
      risk due to the high stresses at the implant and bone. There were no differences
      in stress level, elastic strain at a fracture gap, and bone stress between
      stainless steel and titanium implant. Since the intramedullary canal requires
      reaming to accommodate the retrograde nail, the length of retrograde nail should
      be as long as necessary. However, in case that the retrograde nail can be
      accommodated into the intramedullary canal without reaming, the longer retrograde
      nail can be used. 

PMID- 27032933
TI  - Quantifying Parkinson's disease finger-tapping severity by extracting and
      synthesizing finger motion properties.
AB  - We propose a novel index of Parkinson's disease (PD) finger-tapping severity,
      called "PDFTsi," for quantifying the severity of symptoms related to the finger
      tapping of PD patients with high accuracy. To validate the efficacy of PDFTsi,
      the finger-tapping movements of normal controls and PD patients were measured by
      using magnetic sensors, and 21 characteristics were extracted from the finger
      tapping waveforms. To distinguish motor deterioration due to PD from that due to
      aging, the aging effect on finger tapping was removed from these characteristics.
      Principal component analysis (PCA) was applied to the age-normalized
      characteristics, and principal components that represented the motion properties
      of finger tapping were calculated. Multiple linear regression (MLR) with stepwise
      variable selection was applied to the principal components, and PDFTsi was
      calculated. The calculated PDFTsi indicates that PDFTsi has a high estimation
      ability, namely a mean square error of 0.45. The estimation ability of PDFTsi is
      higher than that of the alternative method, MLR with stepwise regression
      selection without PCA, namely a mean square error of 1.30. This result suggests
      that PDFTsi can quantify PD finger-tapping severity accurately. Furthermore, the
      result of interpreting a model for calculating PDFTsi indicated that motion
      wideness and rhythm disorder are important for estimating PD finger-tapping
      severity. 

PMID- 27032934
TI  - Finding New Tricks for Old Drugs: Tumoricidal Activity of Non-Traditional
      Antitumor Drugs.
AB  - Chemotherapy, a traditional method, plays an important role in tumor therapy.
      Currently, common clinical antitumor drugs have several defects like poor
      efficacy, side effects, etc. Furthermore, developing new antitumor drugs takes a
      long time and requires many resources. Recent studies have found that oldies are
      newbies for the oncologist, such as flavonoid, metformin, aspirin, etc. These non
      traditional antitumor drugs (NTADs) are widely used in management of non-cancer
      diseases, which gained FDA approval for treatment of patients. Increasingly,
      studies about antitumor action of NTADs have attracted many researchers'
      interests. A giant amount of studies showed a decrease in cancer incidence in
      NTAD-treated patients. Several reports outlined a direct inhibitory effect of
      NTADs on cancer cell growth and antitumoral actions. This review summarized the
      research progress on antitumor effects of ten NTADs. Retrospective and meta
      analyses of trials also showed that these NTADs had preventive effects against
      cancer in vitro and in vivo. These drugs represent a promising option for cancer
      treatment, which have clear benefits including clinical safety, obvious curative
      effect, and saving medical and health resources. Judged from previous reports,
      future studies will yield valuable data about the profitable effects of these
      drugs. With a better understanding of its mechanisms of antitumor activity, NTADs
      may become available for combination with chemotherapy or targeted therapy in
      clinic. 

PMID- 27032935
TI  - Assessment of Small Intestinal Transit Times in Ulcerative Colitis and Crohn's
      Disease Patients with Different Disease Activity Using Video Capsule Endoscopy.
AB  - Small intestinal transit times (SITT) influence drug bioavailability. This study
      aimed to compare SITT in Crohn's disease and ulcerative colitis patients with non
      inflammatory bowel disease (IBD) and to determine influence of disease activity
      on transit times, and in addition, to establish the utility of small bowel video
      capsule endoscopy (SB-VCE) in investigation of SITT in IBD patients. A
      retrospective review was performed on consecutive patients who had undergone SB
      VCE at a university hospital out-patient clinic. In total, 125 non-IBD patients,
      55 Crohn's disease patients, and 23 ulcerative colitis patients were included.
      SITT were calculated from the first duodenal image to the first cecal image.
      Disease activity was assessed based on endoscopy results and inflammatory markers
      (calprotectin, C-reactive protein, erythrocyte sedimentation rate). SITT were
      longer in ulcerative colitis patients compared to non-IBD patients (median 264
      min vs. 216 min, p = 0.010). Patients with active Crohn's disease (n = 33) also
      displayed prolonged SITT compared to non-IBD patients (median 253 min vs 216 min,
      p = 0.017) and patients with quiescent Crohn's disease (n = 22) (p = 0.005). SITT
      can be prolonged in IBD patients depending on disease activity which may alter
      the drug release profiles and clinical response to colonic drug delivery systems.
      SB-VCE is a simple, non-invasive tool that can be utilized in pharmacokinetic
      studies to understand drug bioavailability in different patient groups. Moreover,
      this variability in transit times needs to be simulated in dissolution testing
      for in vitro in vivo correlations.

PMID- 27032936
TI  - Conflict in the intensive care unit: Nursing advocacy and surgical agency.
AB  - BACKGROUND: Nurses and surgeons may experience intra-team conflict during
      decision making about the use of postoperative life-sustaining treatment in the
      intensive care unit due to their perceptions of professional roles and
      responsibilities. Nurses have a sense of advocacy-a responsibility to support the
      patient's best interest; surgeons have a sense of agency-a responsibility to keep
      the patient alive. OBJECTIVES: The objectives were to (1) describe the discourse
      surrounding the responsibilities of nurses and surgeons, as "advocates" and
      "agents," and (2) apply these findings to determine how differences in role
      responsibilities could foster conflict during decision making about postoperative
      life-sustaining treatment in the intensive care unit. RESEARCH DESIGN: Articles,
      books, and professional documents were explored to obtain descriptions of nurses'
      and surgeons' responsibilities to their patients. Using discourse analysis,
      responsibilities were grouped into themes and then compared for potential for
      conflict. Ethical considerations: No data were collected from human participants
      and ethical review was not required. The texts were analyzed by a surgeon and a
      nurse to minimize profession-centric biases. FINDINGS: Four themes in nursing
      discourse were identified: responsibility to support patient autonomy regarding
      treatment decisions, responsibility to protect the patient from the physician,
      responsibility to act as an intermediary between the physician and the patient,
      and the responsibility to support the well-being of the patient. Three themes in
      surgery discourse were identified personal responsibility for the patient's
      outcome, commitment to patient survival, and the responsibility to prevent harm
      to the patient from surgery. DISCUSSION: These responsibilities may contribute to
      conflict because each profession is working toward different goals and each
      believes they know what is best for the patient. It is not clear from the
      existing literature that either profession understands each other's
      responsibilities. CONCLUSION: Interventions that improve understanding of each
      profession's responsibilities may be helpful to reduce intra-team conflict in the
      intensive care unit.

PMID- 27032938
TI  - Maintenance of Skin Epithelial Stem Cells by Wnt-3a In Vitro.
AB  - CD49f+ CD34+ cells, a population rich in skin epithelial stem cells (EpSCs), were
      obtained from adult mouse skin and cultured with Wnt-3a for 10 days. On day 10,
      CD49f+ CD34+ cells were sorted and subjected to a second 10-day culture with Wnt
      3a. The same procedures were repeated until fifteenth 10-day culture. CD49f+
      CD34+ cells obtained from each 10-day culture retained the same EpSC
      characteristics as seen in the original EpSCs from adult mouse skin. Here,
      wedescribe the culture protocol using Wnt-3a for successful maintenance of EpSCs.

PMID- 27032937
TI  - Insights into spermine-induced combined high temperature and drought tolerance in
      mung bean: osmoregulation and roles of antioxidant and glyoxalase system.
AB  - High temperature and drought stress often occur simultaneously, and due to global
      climate change, this kind of phenomenon occurs more frequently and severely,
      which exerts devastating effects on plants. Polyamines (PAs) play crucial roles
      in conferring abiotic stress tolerance in plants. Present study investigated how
      exogenous pretreatment of spermine (Spm, 0.2 mM) enhances mung bean (Vigna
      radiata L. cv. BARI Mung-2) seedlings tolerance to high temperature (HT, 40 
      degrees C) and drought [induced by 5 % polyethyleneglycol (PEG)] stress
      individually and in combination. Spm pretreatment reduced reactive oxygen species
      (ROS) production including H2O2 and O2*-, lipoxygenase (LOX) activity, and
      membrane lipid peroxidation (indicated by malondialdehyde, MDA) under HT and/or
      drought stress. Histochemical staining of leaves with diaminobenzidine and nitro
      blue tetrazolium chloride also confirmed that Spm-pretreated seedlings
      accumulated less H2O2 and O2*- under HT and/or drought stress. Spermine
      pretreatment maintained the ascorbate (AsA) and glutathione (GSH) levels high,
      and upregulated the activities of superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPX), dehydroascorbate reductase (DHAR), and glutathione
      reductase (GR) which were vital for imparting ROS-induced oxidative stress
      tolerance under HT and/or drought stress. The cytotoxic compound methylglyoxal
      (MG) was overproduced due to HT and/or drought, but exogenous Spm pretreatment
      reduced MG toxicity enhancing the glyoxalase system. Spermine pretreatment
      modulated endogenous PA levels. Osmoregulation and restoration of plant water
      status were other major contributions of Spm under HT and/or drought stress.
      Preventing photosynthetic pigments and improving seedling growth parameters, Spm
      further confirmed its influential roles in HT and/or drought tolerance.

PMID- 27032939
TI  - Maintenance of Dermal Papilla Cells by Wnt-10b In Vitro.
AB  - Dermal papilla cells (DPCs) are associated with development of hair follicles
      (HFs) and regulation of the hair cycle. However, primary DPCs are known to lose
      their ability to induce HFs after culture in standard media for fibroblasts. We
      examined a new culture condition for DPCs including addition of Wnt-10b, which
      promoted proliferation and maintained their HF induction ability for more than
      ten passages. These results suggest that Wnt-10b plays a pivotal role in
      proliferation and maintenance of DPCs in vitro.

PMID- 27032940
TI  - Isolation and Expansion of Muscle Precursor Cells from Human Skeletal Muscle
      Biopsies.
AB  - One of the major issues concerning human skeletal muscle progenitor cells is
      represented by the efficient isolation and in vitro expansion of cells retaining
      the ability to proliferate, migrate and differentiate once transplanted. Here we
      describe a method (1) effective in obtaining human muscle precursor cells both
      from fresh and frozen biopsies coming from different muscles, (2) selective to
      yield cells uniformly positive for CD56 and negative for CD34 without FACS
      sorting, (3) reliable in maintaining proliferative and in vitro differentiative
      capacity up to passage 10.

PMID- 27032941
TI  - Induction of a Tumor-Metastasis-Receptive Microenvironment as an Unwanted Side
      Effect After Radio/Chemotherapy and In Vitro and In Vivo Assays to Study this
      Phenomenon.
AB  - Besides surgical removal of tumor tissue, chemotherapy and radiotherapy are the
      most important and efficient treatment modalities employed to treat therapy
      susceptible malignancies. The main aim of this treatment-to destroy tumor cells
      is unfortunately usually associated with toxicity to nontumor cells and different
      degrees of tissue and organ damage. In damaged tissues several chemoattractants
      are upregulated and released that may attract tumor cells. Moreover, highly
      migratory radio/chemotherapy treatment may endow cells with several properties of
      cancer stem cells which survive and respond to these chemoattractants upregulated
      in collateral tissues. Based on this, one of the unwanted and underappreciated
      side effects of chemotherapy or radiotherapy is the creation of a metastasis
      receptive microenvironment in bones as well as in other organs of the body.
      Herein we describe methods and assays that can be employed to study migratory
      properties of cancer cells in in vitro (chemotaxis) and in vivo (seeding
      efficiency assay) conditions in response to the induction of pro-metastatic
      microenvironments in various organs and tissues.

PMID- 27032942
TI  - An Effective and Reliable Xeno-free Cryopreservation Protocol for Single Human
      Pluripotent Stem Cells.
AB  - Efficient cryopreservation of human pluripotent stem cells (hPSCs) in chemically
      defined, xeno-free conditions is highly desirable for medical research and
      clinical applications such as cell-based therapies. Here we present a simple and
      effective slow freezing-rapid thawing protocol for the cryopreservation of feeder
      free, single hPSCs. This cryopreservation protocol involves the supplementation
      of 10 % dimethyl sulfoxide (DMSO) and 10 MUM Rho-associated kinase inhibitor Y
      27632 into two types of xeno-free, defined media supplements (Knockout Serum
      Replacement and TeSR2). High post-thaw cell recovery (~90 %) and cell expansion
      (~70 %) can be achieved using this protocol. The cryopreserved single cells
      retain the morphological characteristics of hPSCs and differentiation
      capabilities of pluripotent stem cells.

PMID- 27032943
TI  - Stencil Micropatterning for Spatial Control of Human Pluripotent Stem Cell Fate
      Heterogeneity.
AB  - Human pluripotent stem cells (hPSCs) have the intrinsic ability to differentiate
      and self-organize into distinct tissue patterns, although this requires the
      presentation of spatial environmental cues, i.e., biochemical and mechanical
      gradients. Cell micropatterning technologies potentially offer the means to
      spatially control stem cell microenvironments and organize the resultant
      differentiation fates. Here, we describe stencil micropatterning as a simple and
      robust method to generate hPSC micropatterns for controlling hPSC differentiation
      patterns. hPSC micropatterns are specified by the geometries of the cell stencil
      through-holes, which physically confine the locations where the underlying
      extracellular matrix and hPSCs can access and attach to the substrate. This
      confers the unique capability of stencil micropatterning to work with a variety
      of culture substrates and extracellular matrices for optimal hPSC culture. We
      present the detailed steps of stencil micropatterning to successfully generate
      hPSC micropatterns, which can be used to investigate how spatial polarization of
      cell adhesion results in cell fate heterogeneity.

PMID- 27032944
TI  - Induction of Inner Ear Hair Cells from Mouse Embryonic Stem Cells In Vitro.
AB  - Inner ear hair cells (HCs) function as the primary transducers for perception of
      sound and balance, while a defect in their formation or their loss results in
      sensory deficits. In mammals, once HCs are lost, they are not regenerated, and
      thus, various medical strategies have been proposed for their reproduction.
      Although embryonic stem (ES) cells are a promising source for cell therapy,
      little is known about efficient generation of hair cell-like cells (HCLs) from
      mouse ES cells. In the present protocol, we describe a simple method for
      obtaining ES-derived murine HCLs (HIST2 method).

PMID- 27032945
TI  - Isolation and Characterization of Cancer Stem Cells of the Non-Small-Cell Lung
      Cancer (A549) Cell Line.
AB  - Cancer is a major health problem worldwide. The failure of current treatments to
      completely eradicate cancer cells often leads to cancer recurrence and
      dissemination. Studies have suggested that tumor growth and spread are driven by
      a minority of cancer cells that exhibit characteristics similar to those of
      normal stem cells, thus these cells are called cancer stem cells (CSCs). CSCs are
      believed to play an important role in initiating and promoting cancer. CSCs are
      resistant to currently available cancer therapies, and understanding the
      mechanisms that control the growth of CSCs might have great implications for
      cancer therapy. Cancer cells are consist of heterogeneous population of cells,
      thus methods of identification, isolation, and characterisation of CSCs are
      fundamental to obtain a pure CSC populations. Therefore, this chapter describes
      in detail a method for isolating and characterizing a pure population of CSCs
      from heterogeneous population of cancer cells and CSCs based on specific cell
      surface markers.

PMID- 27032946
TI  - In Vitro Culture of Human Hematopoietic Stem Cells in Serum Free Medium and Their
      Monitoring by Flow Cytometry.
AB  - Hematopoietic stem cells can be isolated from human blood cells trapped in
      leukoreduction systems. The leukoreduction systems filters or chambers are
      usually discarded from routine blood or platelet donations in blood banks around
      the world. These CD34+ cells are a good source of normal stem cells and can be
      used as models to characterize the blood stem cells before and after culture in
      vitro. This chapter contains detailed methodologies for the isolation of stem
      cells from peripheral blood, the culture of these cells in a medium exempt of
      animal proteins and for the flow cytometry analysis of the resulting cell
      population for the characterization of their differentiation.

PMID- 27032947
TI  - The Gut Microbiome in the NOD Mouse.
AB  - The microbiome (or microbiota) are an ecological community of commensal,
      symbiotic, and pathogenic microorganisms that outnumber the cells of the human
      body tenfold. These microorganisms are most abundant in the gut where they play
      an important role in health and disease. Alteration of the homeostasis of the gut
      microbiota can have beneficial or harmful consequences to health. There has
      recently been a major increase in studies on the association of the gut
      microbiome composition with disease phenotypes.The nonobese diabetic (NOD) mouse
      is an excellent mouse model to study spontaneous type 1 diabetes development. We,
      and others, have reported that gut bacteria are critical modulators for type 1
      diabetes development in genetically susceptible NOD mice.Here we present our
      standard protocol for gut microbiome analysis in NOD mice that has been routinely
      implemented in our research laboratory. This incorporates the following steps:
      (1) Isolation of total DNA from gut bacteria from mouse fecal samples or
      intestinal contents; (2) bacterial DNA sequencing, and (3) basic data analysis.

PMID- 27032948
TI  - Perfusion Stirred-Tank Bioreactors for 3D Differentiation of Human Neural Stem
      Cells.
AB  - Therapeutic breakthroughs in neurological disorders have been hampered by the
      lack of accurate central nervous system (CNS) models. The development of these
      models allows the study of the disease onset/progression mechanisms and the
      preclinical evaluation of new therapeutics. This has traditionally relied on
      genetically engineered animal models that often diverge considerably from the
      human phenotype (developmental, anatomic, and physiological) and 2D in vitro cell
      models, which fail to recapitulate the characteristics of the target tissue (cell
      cell and cell-matrix interactions, cell polarity, etc.). Recapitulation of CNS
      phenotypic and functional features in vitro requires the implementation of
      advanced culture strategies, such as 3D culture systems, which enable to mimic
      the in vivo structural and molecular complexity. Models based on differentiation
      of human neural stem cells (hNSC) in 3D cultures have great potential as
      complementary tools in preclinical research, bridging the gap between human
      clinical studies and animal models. The development of robust and scalable
      processes for the 3D differentiation of hNSC can improve the accuracy of early
      stage development in preclinical research. In this context, the use of software
      controlled stirred-tank bioreactors (STB) provides an efficient technological
      platform for hNSC aggregation and differentiation. This system enables to monitor
      and control important physicochemical parameters for hNSC culture, such as
      dissolved oxygen. Importantly, the adoption of a perfusion operation mode allows
      a stable flow of nutrients and differentiation/neurotrophic factors, while
      clearing the toxic by-products. This contributes to a setting closer to the
      physiological, by mimicking the in vivo microenvironment. In this chapter, we
      address the technical requirements and procedures for the implementation of 3D
      differentiation strategies of hNSC, by operating STB under perfusion mode for
      long-term cultures. This strategy is suitable for the generation of human 3D
      neural in vitro models, which can be used to feed high-throughput screening
      platforms, contributing to expand the available in vitro tools for drug screening
      and toxicological studies.

PMID- 27032950
TI  - Expansion of Human Mesenchymal Stem Cells in a Microcarrier Bioreactor.
AB  - Human mesenchymal stem cells (hMSCs) are considered as a primary candidate in
      cell therapy owing to their self-renewability, high differentiation capabilities,
      and secretions of trophic factors. In clinical application, a large quantity of
      therapeutically competent hMSCs is required that cannot be produced in
      conventional petri dish culture. Bioreactors are scalable and have the capacity
      to meet the production demand. Microcarrier suspension culture in stirred-tank
      bioreactors is the most widely used method to expand anchorage dependent cells in
      a large scale. Stirred-tank bioreactors have the potential to scale up and
      microcarriers provide the high surface-volume ratio. As a result, a spinner flask
      bioreactor with microcarriers has been commonly used in large scale expansion of
      adherent cells. This chapter describes a detailed culture protocol for hMSC
      expansion in a 125 mL spinner flask using microcarriers, Cytodex I, and a
      procedure for cell seeding, expansion, metabolic sampling, and quantification and
      visualization using microculture tetrazolium (MTT) reagent.

PMID- 27032949
TI  - A Bioreactor to Apply Multimodal Physical Stimuli to Cultured Cells.
AB  - Cells residing in the cardiac niche are constantly experiencing physical stimuli,
      including electrical pulses and cyclic mechanical stretch. These physical signals
      are known to influence a variety of cell functions, including the secretion of
      growth factors and extracellular matrix proteins by cardiac fibroblasts, calcium
      handling and contractility in cardiomyocytes, or stretch-activated ion channels
      in muscle and non-muscle cells of the cardiovascular system. Recent progress in
      cardiac tissue engineering suggests that controlled physical stimulation can lead
      to functional improvements in multicellular cardiac tissue constructs. To study
      these effects, aspects of the physical environment of the myocardium have to be
      mimicked in vitro. Applying continuous live imaging, this protocol demonstrates
      how a specifically designed bioreactor system allows controlled exposure of
      cultured cells to cyclic stretch, rhythmic electrical stimulation, and controlled
      fluid perfusion, at user-defined temperatures.

PMID- 27032952
TI  - Retraction Note to: Correlation of ESR, C3, C4, anti-DNA and lupus activity based
      on British Isles Lupus Assessment Group Index in patients of rheumatology clinic.
      Rheumatol Int (2010)30:1605-9.

PMID- 27032951
TI  - Molecular Methods and Protein Synthesis for Definition of Autoantibody Epitopes.
AB  - Epitope mapping is the process of experimentally identifying the binding sites,
      or "epitopes," of antibodies on their target antigens. Understanding the antibody
      epitope interaction provides a basis for the rational design of potential
      preventative vaccines. Islet autoantibodies are currently the best available
      biomarkers for predicting future type 1 diabetes. These include autoantibodies to
      the islet beta cell proteins, insulin and the tyrosine phosphatase islet antigen
      2 (IA-2) which selectively bind to a small number of dominant epitopes associated
      with increased risk of disease progression. The major epitope regions of insulin
      and IA-2 autoantibodies have been identified, but need to be mapped more
      precisely. In order to characterize these epitopes more accurately, this article
      describes the methods of cloning and mutagenesis of insulin and IA-2 and
      subsequent purification of the proteins that can be tested in displacement
      analysis and used to monitor immune responses, in vivo, to native and mutated
      proteins in a humanized mouse model carrying the high-risk HLA class II
      susceptibility haplotype DRB1*04-DQ8.

PMID- 27032953
TI  - Multiple domains of parental secure base support during childhood and adolescence
      contribute to adolescents' representations of attachment as a secure base script.
AB  - Although attachment theory claims that early attachment representations
      reflecting the quality of the child's "lived experiences" are maintained across
      developmental transitions, evidence that has emerged over the last decade
      suggests that the association between early relationship quality and adolescents'
      attachment representations is fairly modest in magnitude. We used aspects of
      parenting beyond sensitivity over childhood and adolescence and early security to
      predict adolescents' scripted attachment representations. At age 18 years, 673
      participants from the NICHD Study of Early Child Care and Youth Development
      completed the Attachment Script Assessment from which we derived an assessment of
      secure base script knowledge. Measures of secure base support from childhood
      through age 15 years (e.g., parental monitoring of child activity, father
      presence in the home) were selected as predictors and accounted for an additional
      8% of the variance in secure base script knowledge scores above and beyond direct
      observations of sensitivity and early attachment status alone, suggesting that
      adolescents' scripted attachment representations reflect multiple domains of
      parenting. Cognitive and demographic variables also significantly increased
      predicted variance in secure base script knowledge by 2% each.

PMID- 27032954
TI  - Factors Affecting Age at ASD Diagnosis in UK: No Evidence that Diagnosis Age has
      Decreased Between 2004 and 2014.
AB  - Clinical initiatives have aimed to reduce the age at ASD diagnosis in the UK.
      This study investigated whether the median age at diagnosis in childhood has
      reduced in recent years, and identified the factors associated with earlier
      diagnosis in the UK. Data on 2134 children with ASD came from two large family
      databases. Results showed that the age of ASD diagnosis has not decreased. The
      median age of diagnosis of all ASDs was 55 months. Factors associated with
      earlier age of diagnosis were autism diagnosis (compared with other ASD),
      language regression, language delay, lower socioeconomic status, and greater
      degree of support required. Effective clinical strategies are needed to identify
      children with characteristics that have in the past delayed ASD diagnosis.

PMID- 27032955
TI  - Cloning and molecular characterization of a putative voltage-gated sodium channel
      gene in the crayfish.
AB  - Voltage-gated sodium channel genes and associated proteins have been cloned and
      studied in many mammalian and invertebrate species. However, there is no data
      available about the sodium channel gene(s) in the crayfish, although the animal
      has frequently been used as a model to investigate various aspects of neural
      cellular and circuit function. In the present work, by using RNA extracts from
      crayfish abdominal ganglia samples, the complete open reading frame of a putative
      sodium channel gene has firstly been cloned and molecular properties of the
      associated peptide have been analyzed. The open reading frame of the gene has a
      length of 5793 bp that encodes for the synthesis of a peptide, with 1930 amino
      acids, that is 82% similar to the alpha-peptide of a sodium channel in a
      neighboring species, Cancer borealis. The transmembrane topology analysis of the
      crayfish peptide indicated a pattern of four folding domains with several
      transmembrane segments, as observed in other known voltage-gated sodium channels.
      Upon analysis of the obtained sequence, functional regions of the putative sodium
      channel responsible for the selectivity filter, inactivation gate, voltage
      sensor, and phosphorylation have been predicted. The expression level of the
      putative sodium channel gene, as defined by a qPCR method, was measured and found
      to be the highest in nervous tissue.

PMID- 27032956
TI  - Small Bowel Endoscopy.
AB  - OPINION STATEMENT: The small bowel is a challenging area for endoscopic
      evaluation and therapy due to its length and angulated configuration. A small
      lumen diameter and segmental peristalsis made it a perfect fit for examination by
      a novel ingestible wireless camera in a capsule. The development of capsule
      endoscopy changed the diagnosis and management of bleeding lesions, ulcers, and
      tumors deep in the small bowel, allowing earlier diagnosis with excellent patient
      acceptance. Device-assisted enteroscopy revolutionized small bowel therapy,
      particularly management of bleeding, Peutz-Jeghers polyposis, and tumor marking
      for minimally invasive surgery. Small bowel stricture dilation in select patients
      is safe and effective. Tools for a spectrum of small bowel therapies are
      available but remain suboptimal to tackle lesions on angulated folds deep in the
      small bowel. Universal terminology to describe the endoscopic appearance of
      vascular lesions will facilitate studies of endoscopic and medical therapy. The
      future holds improvements in imaging, easier advancement through the small bowel,
      and therapeutic capacity. This review focuses on methods of small bowel
      endoscopy, therapy, and outcomes.

PMID- 27032957
TI  - Inherently-Forced Tensile Strain in Nanodiamond-Derived Onion-like Carbon:
      Consequences in Defect-Induced Electrochemical Activation.
AB  - We analyzed the nanodiamond-derived onion-like carbon (OLC) as function of
      synthesis temperature (1000~1400  degrees C), by high-resolution electron
      microscopy, electron energy loss spectroscopy, visible-Raman spectroscopy,
      ultraviolet photoemission spectroscopy, impedance spectroscopy, cyclic
      voltammetry and differential pulse voltammetry. The temperature dependences of
      the obtained properties (averaged particle size, tensile strain, defect density,
      density of states, electron transfer kinetics, and electrochemical oxidation
      current) unanimously coincided: they initially increased and saturated at 1200 
      degrees C. It was attributed to the inherent tensile strains arising from (1) the
      volume expansion associated with the layer-wise diamond-to-graphite
      transformation of the core, which caused forced dilation of the outer shells
      during their thermal synthesis; (2) the extreme curvature of the shells. The
      former origin was dominant over the latter at the outermost shell, of which the
      relevant evolution in defect density, DOS and electron transfer kinetics
      determined the electrochemical performances. In detection of dopamine (DA), uric
      acid (UA) and ascorbic acid (AA) using the OLC as electrode, their oxidation peak
      currents were enhanced by factors of 15~60 with annealing temperature. Their
      limit of detection and the linear range of detection, in the post-treatment-free
      condition, were as excellent as those of the nano-carbon electrodes post-treated
      by Pt-decoration, N-doping, plasma, or polymer. 

PMID- 27032958
TI  - ERP evidence for own-age effects on late stages of processing sad faces.
AB  - Faces convey important information on interaction partners, such as their
      emotional state and age. Faces of the same age are, according to recent research,
      preferentially processed. The aim of the present study was to investigate whether
      the neural processes underlying this own-age effect are influenced by the
      emotional expression of the face, and to explore possible explanations such as
      the frequency or quality of contact to own-age versus other-age groups. Event
      related potentials were recorded while 19 younger (18-30 years) and 19 older (64
      86 years) observers watched younger and older sad and happy faces. Sad but not
      happy faces elicited higher late positive potential amplitudes for own-age than
      for other-age faces. This own-age effect was significant for older, but not for
      younger, observers, and correlated with the quality of contact with the own-age
      versus the other-age group. This pattern suggests that sad own-age faces are
      motivationally more relevant.

PMID- 27032959
TI  - Prior exposure to extreme pain alters neural response to pain in others.
AB  - In the extant literature examining the brain mechanisms implicated in pain
      perception, researchers have theorized that the overlapping responses to pain in
      the self and in others mark the human capacity for empathy. Here we investigated
      how prior exposure to extreme pain affects pain perception, by assessing the
      dynamics of pain processing in veterans who were previously exposed to severe
      injury. Forty-three participants (28 pain-exposed and 15 controls) underwent
      whole-head magnetoencephalography (MEG) while viewing photographs of limbs in
      painful and nonpainful (neutral) conditions. Among controls, an early (0-220 ms)
      "pain effect" in the posterior cingulate and sensorimotor cortices, and a later
      (760-900 ms) "pain effect" in the posterior cingulate cortex, superior temporal
      gyrus/insula, and fusiform gyrus were found, indicated by enhanced alpha
      suppression to the pain versus nonpain conditions. Importantly, pain-exposed
      participants exhibited an atypical pain response in the posterior cingulate
      cortex, indicated by a normative response to pain, but no pain-to-no-pain
      differentiation. This may suggest that individuals exposed to extreme pain may
      perceive neutral stimuli as potentially threatening. Our findings demonstrate
      alterations in pain perception following extreme pain exposure, chart the
      sequence from automatic to evaluative pain processing, and emphasize the
      importance of considering past experiences in studying the neural response to
      others' states.

PMID- 27032960
TI  - Determination of optimal excitation patterns for local mechanical inner ear
      stimulation using a physiologically-based model.
AB  - Within the field of hearing prosthetics it is known that patients with sufficient
      residual hearing benefit from the simultaneous employment of hearing aid and
      cochlear implant. Several attempts have been proposed to combine the sources of
      the corresponding acoustic and electric stimuli in a single, implantable device.
      However, since only little is known about the effect of also applying the
      acoustic stimulus locally from within the inner ear, the current state of
      research lacks detailed knowledge on the optimal stimulation at the corresponding
      bionic interface. Within this manuscript, a simple but yet physiologically-based
      inner ear model is presented which was designed specifically for the analysis of
      local acoustic or mechanical inner ear stimulation. A detailed model analysis is
      performed showing that it is capable of mirroring the known mechanical phenomena
      of this particular stimulation approach. Using the model, it is demonstrated how
      amplitude and phase shift values of stimuli applied from within the inner ear
      should be chosen for optimal inner ear stimulation. 

PMID- 27032961
TI  - The management of large staghorn renal stones by percutaneous versus laparoscopic
      versus open nephrolithotomy: a comparative analysis of clinical efficacy and
      functional outcome.
AB  - The objective of this study was to analyze the outcome of percutaneous
      nephrolithotomy (PCNL), laparoscopic and open anatrophic nephrolithotomy (AN) for
      management of patients with large staghorn renal stones. We analyzed the peri
      operative parameters, overall treatment costs and changes in the function of the
      affected kidney on technetium-99 dimercaptosuccinic acid renal scintigraphy, done
      before the operation and before the final follow-up visit, in 45 adults who
      underwent PCNL (n = 16) versus laparoscopic (n = 15) versus open (n = 14) AN for
      large staghorn renal stones. All three groups had statistically similar
      preoperative characteristics, including the function of the operated kidney on
      renal scan. On the discharge day, the PCNL group had the lowest stone-free rate
      (43.75 %) compared to the laparoscopic (80 %) and open AN groups (92.85 %) (P =
      0.009). After a mean follow-up period of 12.1 months, the decrease in the
      function of the operated kidney was greatest in the open AN group (-8.66 +/-
      4.97) compared to the laparoscopic AN (-6.04 +/- 6.52) and PCNL group (-2.12 +/-
      2.77) (P = 0.003). The need for ancillary procedures to manage residual stones
      was greatest in the PCNL group and lowest in the open AN group. A similar trend
      was seen in overall treatment costs (P < 0.001). For management of large staghorn
      renal stones, the more invasive the procedure, the higher the one-session stone
      free rate and the lower the need for ancillary procedures; however, greater renal
      functional loss can be anticipated. The need for ancillary procedures is a major
      determining factor in the overall cost of treatment, which was highest in the
      PCNL group.

PMID- 27032962
TI  - Size and shape-integration of morphometrics, mathematical modelling,
      developmental and evolutionary biology.

PMID- 27032963
TI  - Bus fare discounts for senior citizens should be taken and used.

PMID- 27032964
TI  - Irritable bowel syndrome among nurses working in King Abdulaziz University
      Hospital, Jeddah, Saudi Arabia.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal
      disorder that can cause disability and economic burden. Nurses are a vital part
      of the medical team and their well-being is an important issue. Yet, few studies
      have been done concerning IBS among nurses. OBJECTIVES: To determine the
      prevalence, severity, and predictors of IBS among nurses working at King
      Abdulaziz University Hospital, Jeddah, Saudi Arabia. MATERIALS AND METHODS: A
      cross-sectional study was conducted among 229 nurses who fulfilled the
      eligibility criteria. They were selected by stratified random sampling during
      2014-2015. A validated, confidential, self-administered data collection sheet was
      used for collection of personal and sociodemographic data. Rome III Criteria, IBS
      Severity Scoring System (IBS-SSS), Hospital Anxiety and Depression Scale (HADS),
      and Pittsburgh Sleep Quality Index (PSQI) were included. Both descriptive and
      inferential statistics were done. A multiple logistic regression analysis was
      done to determine the predictors of IBS. RESULTS: The prevalence of IBS among
      nurses was 14.4%, and IBS-Mixed type was the commonest variety (54.5%). Positive
      family history of IBS, working in outpatient clinics, having day shift, poor
      sleep quality, and high anxiety and depression scale scores were significantly
      associated with IBS. After controlling for confounding factors in regression
      analysis, the predictors of IBS were food hypersensitivity (aOR=4.52; 95% CI:
      1.80-11.33), morbid anxiety (aOR=4.34; 95% CI: 1.49-12.67), and positive family
      history of IBS (aOR=3.38; 95% CI: 1.12-13.23). CONCLUSION: The prevalence of IBS
      was 14.4%. Food hypersensitivity, morbid anxiety, and family history were the
      predictors of IBS. Screening and management of IBS, food hypersensitivity, and
      psychological problems among nurses are recommended.

PMID- 27032965
TI  - Asymmetric Formal Aza-Diels-Alder Reaction of Trifluoromethyl Hemiaminals with
      Enones Catalyzed by Primary Amines.
AB  - A primary amine-catalyzed asymmetric formal aza-Diels-Alder reaction of
      trifluoromethyl hemiaminals with enones was developed via a chiral gem-diamine
      intermediate. This novel protocol allowed facile access to structurally diverse
      trifluoromethyl-substituted piperidine scaffolds with high stereoselectivity. The
      utility of this method was further demonstrated through a concise approach to
      biologically active 4-hydroxypiperidine. More importantly, a stepwise mechanism
      involving an asymmetric induction process was proposed to rationalize the
      positive correlation between the chirality of the gem-diamine intermediate and
      the formal aza-Diels-Alder product. 

PMID- 27032967
TI  - Comparison of medical costs and healthcare resource utilization of post
      menopausal women with HR+/HER2- metastatic breast cancer receiving everolimus
      based therapy or chemotherapy: a retrospective claims database analysis.
AB  - OBJECTIVE: To analyze medical costs and healthcare resource utilization (HRU)
      associated with everolimus-based therapy or chemotherapy among post-menopausal
      women with hormone-receptor-positive, human-epidermal-growth-factor-receptor-2
      negative (HR+/HER2-) metastatic breast cancer (mBC). METHODS: Patients with
      HR+/HER2- mBC who discontinued a non-steroidal aromatase inhibitor and began a
      new line of treatment with everolimus-based therapy or chemotherapy (index
      therapy/index date) between July 20, 2012 and April 30, 2014 were identified from
      two large claims databases. All-cause, BC-related, and adverse event (AE)-related
      medical costs (in 2014 USD) and all-cause HRU per patient per month (PPPM) were
      analyzed for both treatment groups across patients' first four lines of therapies
      for mBC. Adjusted differences in costs and HRU between the everolimus and
      chemotherapy treatment group were estimated pooling all lines and using
      multivariable generalized linear models, accounting for difference in patient
      characteristics. RESULTS: A total of 3298 patients were included: 902 everolimus
      treated patients and 2636 chemotherapy-treated patients. Compared to
      chemotherapy, everolimus was associated with significantly lower all-cause
      (adjusted mean difference = $3455, p < 0.01) and BC-related ($2510, p < 0.01)
      total medical costs, with inpatient ($1344, p < 0.01) and outpatient costs
      ($1048, p < 0.01) as the main drivers for cost differences. Everolimus was also
      associated with significantly lower AE-related medical costs ($1730, p < 0.01),
      as well as significantly lower HRU (emergency room incidence rate ratio [IRR] =
      0.83; inpatient IRR = 0.74; inpatient days IRR = 0.65; outpatient IRR = 0.71; BC
      related outpatient IRR = 0.57; all p < 0.01). CONCLUSIONS: This retrospective
      claims database analysis of commercially-insured patients with HR+/HER2- mBC in
      the US showed that everolimus was associated with substantial all-cause, BC
      related, and AE-related medical cost savings and less utilization of healthcare
      resources relative to chemotherapy.

PMID- 27032966
TI  - Controlled rotation mechanism of DNA strand exchange by the Hin serine
      recombinase.
AB  - DNA strand exchange by serine recombinases has been proposed to occur by a large
      scale rotation of halves of the recombinase tetramer. Here we provide the first
      direct physical evidence for the subunit rotation mechanism for the Hin serine
      invertase. Single-DNA looping assays using an activated mutant (Hin-H107Y) reveal
      specific synapses between two hix sites. Two-DNA "braiding" experiments, where
      separate DNA molecules carrying a single hix are interwound, show that Hin-H107Y
      cleaves both hix sites and mediates multi-step rotational relaxation of the
      interwinding. The variable numbers of rotations in the DNA braid experiments are
      in accord with data from bulk experiments that follow DNA topological changes
      accompanying recombination by the hyperactive enzyme. The relatively slow Hin
      rotation rates, combined with pauses, indicate considerable rotary friction
      between synapsed subunit pairs. A rotational pausing mechanism intrinsic to
      serine recombinases is likely to be crucial for DNA ligation and for preventing
      deleterious DNA rearrangements. 

PMID- 27032968
TI  - Analytic TOF PET reconstruction algorithm within DIRECT data partitioning
      framework.
AB  - Iterative reconstruction algorithms are routinely used for clinical practice;
      however, analytic algorithms are relevant candidates for quantitative research
      studies due to their linear behavior. While iterative algorithms also benefit
      from the inclusion of accurate data and noise models the widespread use of time
      of-flight (TOF) scanners with less sensitivity to noise and data imperfections
      make analytic algorithms even more promising. In our previous work we have
      developed a novel iterative reconstruction approach (DIRECT: direct image
      reconstruction for TOF) providing convenient TOF data partitioning framework and
      leading to very efficient reconstructions. In this work we have expanded DIRECT
      to include an analytic TOF algorithm with confidence weighting incorporating
      models of both TOF and spatial resolution kernels. Feasibility studies using
      simulated and measured data demonstrate that analytic-DIRECT with appropriate
      resolution and regularization filters is able to provide matched bias versus
      variance performance to iterative TOF reconstruction with a matched resolution
      model. 

PMID- 27032969
TI  - Electrophysiologic Validation of Diffusion Tensor Imaging Tractography during
      Deep Brain Stimulation Surgery.
AB  - BACKGROUND AND PURPOSE: Diffusion tensor imaging fiber tractography-assisted
      planning of deep brain stimulation is an emerging technology. We investigated its
      accuracy by using electrophysiology under clinical conditions. We hypothesized
      that a level of concordance between electrophysiology and DTI fiber tractography
      can be reached, comparable with published modeling approaches for deep brain
      stimulation surgery. MATERIALS AND METHODS: Eleven patients underwent subthalamic
      nucleus deep brain stimulation. DTI scans and high-resolution T1- and T2-weighted
      MR imaging was performed at 3T. Corticospinal tracts were traced. We studied
      electrode positions and current amplitudes that elicited corticospinal tract
      effects during the operation to determine relative corticospinal tract distance.
      Postoperatively, 3D deep brain stimulation electrode contact locations and
      stimulation patterns were applied for the same corticospinal tract distance
      estimation. RESULTS: Intraoperative electrophysiologic (n = 40) clinical effects
      in 11 patients were detected. The mean intraoperative electrophysiologic
      corticospinal tract distance was 3.0 +/- 0.6 mm; the mean image-derived
      corticospinal tract distance (DTI fiber tractography) was 3.0 +/- 1.3 mm. The 95%
      limits of agreement were +/-2.4 mm. Postoperative electrophysiology (n = 44)
      corticospinal tract activation effects were encountered in 9 patients; 39 were
      further evaluated. Mean electrophysiologic corticospinal tract distance was 3.7
      +/- 0.7 mm; for DTI fiber tractography, it was 3.2 +/- 1.9 mm. The 95% limits of
      agreement were +/-2.5 mm. CONCLUSIONS: DTI fiber tractography depicted the medial
      corticospinal tract border with proved concordance. Although the overall range of
      measurements was relatively small and variance was high, we believe that further
      use of DTI fiber tractography to assist deep brain stimulation procedures is
      advisable if inherent limitations are respected. These results confirm our
      previously published electric field simulation studies.

PMID- 27032970
TI  - Do Radiologists Report the TNM Staging in Radiology Reports for Head and Neck
      Cancers? A National Survey Study.
AB  - BACKGROUND AND PURPOSE: CT and MR imaging are widely used for the staging of head
      and neck cancer. Currently, there are no data regarding whether the primary
      tumor, nodes, metastasis (TNM) staging is routinely incorporated into radiology
      reports. We conducted a national survey to determine whether radiologists
      routinely address staging, in particular regarding T (primary tumor) and N
      (nodal). MATERIALS AND METHODS: The survey was sent to 782 members of the
      American Society of Head and Neck Radiology. The survey asked whether they assign
      TN staging in reports. If they do assign TN staging, what are the reasons for
      doing so, and if not, what are the barriers or reasons for not including it in
      the radiology report? The method of measuring the size of the primary tumor and
      pathologic lymph nodes was also queried. RESULTS: A total of 229 responses were
      returned (29.3% response rate). Approximately half (49%; 95% confidence interval,
      43.55-54.5%) of the responders thought that incorporating TN staging is
      important. However, only 24.5% (95% confidence interval, 19.8%-29.2%) stated that
      they routinely assigned TN staging in their radiology reports. The most common
      barriers were being afraid of being inaccurate (59%) and being unable to remember
      the staging classifications (58.2%); 76.9% indicated that they measure a primary
      tumor in 3D. CONCLUSIONS: Staging head and neck cancer based on imaging presents
      unique challenges. Nearly half of the responding radiologists think it is
      important to incorporate TN staging in radiology reports, though only a quarter
      of them routinely do so in practice.

PMID- 27032971
TI  - Assessment of Collateral Status by Dynamic CT Angiography in Acute MCA Stroke:
      Timing of Acquisition and Relationship with Final Infarct Volume.
AB  - BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of
      collateral filling in patients with acute ischemic stroke. Our aim was to
      describe collateral filling with dynamic CTA and assess the relationship with
      infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with
      acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT,
      single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after
      stroke onset. For each patient, a detailed assessment of the extent and velocity
      of arterial filling was obtained. Poor radiologic outcome was defined as an
      infarct volume of >=70 mL. The association between collateral score and follow-up
      infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients
      with a mean age of 67 years were included. For all patients combined, the
      interval that contained the peak of arterial filling in both hemispheres was
      between 11 and 21 seconds after ICA contrast entry. Poor collateral status as
      assessed with dynamic CTA was more strongly associated with infarct volume of
      >=70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk
      ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus
      slow collaterals) were analyzed separately; the results showed that compared with
      good and fast collaterals, a similar risk ratio was found for patients with good
      but-slow collaterals (risk ratio, 1.3; 95% CI, 0.7-2.4). CONCLUSIONS: Dynamic CTA
      provides a more detailed assessment of collaterals than single-phase CTA and has
      a stronger relationship with infarct volume at follow-up. The extent of
      collateral flow is more important in determining tissue fate than the velocity of
      collateral filling. The timing of dynamic CTA acquisition in relation to
      intravenous contrast administration is critical for the optimal assessment of the
      extent of collaterals.

PMID- 27032972
TI  - T1 Signal-Intensity Increase in the Dentate Nucleus after Multiple Exposures to
      Gadodiamide: Intraindividual Comparison between 2 Commonly Used Sequences.
AB  - BACKGROUND AND PURPOSE: Different T1-weighted sequences have been used for
      qualitative and quantitative evaluation of T1 signal intensity related to
      gadolinium deposition in the dentate nucleus in patients who underwent several
      enhanced MR imaging studies. Our purpose was to perform an intraindividual
      qualitative and quantitative comparison between T1-weighted spin-echo and 3D
      magnetization-prepared rapid acquisition of gradient echo sequences in patients
      who had multiple exposures to gadodiamide. MATERIALS AND METHODS: Our
      retrospectively selected population included 18 patients who underwent at least 3
      administrations of gadodiamide and had a baseline and a final MR imaging
      performed with both T1-weighted sequences. Qualitative and quantitative analyses
      were independently performed. Dentate nucleus/middle cerebellar peduncle signal
      intensity ratios and signal changes between the baseline and final examinations
      were compared by using the Wilcoxon signed rank test. Correlation between
      quantitative and qualitative evaluations was assessed by using a polyserial
      correlation test. RESULTS: The differences between the 2 sequences for both
      baseline and last examination dentate nucleus/middle cerebellar peduncle ratios
      were statistically significant (P = .008 and P = .006, respectively); however,
      the signal-intensity changes of the ratios with time were not (P = .64). The
      correlation between the qualitative and quantitative analysis was very strong
      (near-perfect) (r = 0.9) for MPRAGE and strong (r = 0.63) for spin-echo
      sequences. CONCLUSIONS: T1-weighted spin-echo and MPRAGE sequences cannot be used
      interchangeably for qualitative or quantitative analysis of signal intensity in
      the dentate nucleus in patients who received gadodiamide. Baseline and final
      examination ratios should be evaluated across time by using the same sequence.
      Qualitative analysis performed with MPRAGE correlated better with quantitative
      analysis and may offer advantages over spin-echo sequences for research purposes.

PMID- 27032973
TI  - Limitations of T2*-Gradient Recalled-Echo and Susceptibility-Weighted Imaging in
      Characterizing Chronic Subdural Hemorrhage in Infant Survivors of Abusive Head
      Trauma.
AB  - A possible misconception among radiologists is that chronic subdural hemorrhage
      should show some degree of blooming on T2*-gradient recalled-echo or
      susceptibility-weighted sequences such as SWI and susceptibility-weighted
      angiography, which is not necessarily true. We present 5 cases of chronic
      subdural hemorrhages in infants, demonstrating intensity near or greater than
      that of CSF with variable amounts of hemosiderin staining along the neomembranes.
      We review the physiology and MR imaging physics behind the appearance of a
      chronic subdural hemorrhage, highlighting that the absence of a BBB can allow
      hemosiderin to be completely removed from the subdural compartment. Finally, we
      stress the importance of reviewing all multiplanar sequences for the presence of
      neomembranes, which can be quite subtle in the absence of hemosiderin staining
      and are critical for making the diagnosis of chronic subdural hemorrhage.

PMID- 27032974
TI  - Development of the Fetal Vermis: New Biometry Reference Data and Comparison of 3
      Diagnostic Modalities-3D Ultrasound, 2D Ultrasound, and MR Imaging.
AB  - BACKGROUND AND PURPOSE: Normal biometry of the fetal posterior fossa rules out
      most major anomalies of the cerebellum and vermis. Our aim was to provide new
      reference data of the fetal vermis in 4 biometric parameters by using 3 imaging
      modalities, 2D ultrasound, 3D ultrasound, and MR imaging, and to assess the
      relation among these modalities. MATERIALS AND METHODS: A retrospective study was
      conducted between June 2011 and June 2013. Three different imaging modalities
      were used to measure vermis biometry: 2D ultrasound, 3D ultrasound, and MR
      imaging. The vermian parameters evaluated were the maximum superoinferior
      diameter, maximum anteroposterior diameter, the perimeter, and the surface area.
      Statistical analysis was performed to calculate centiles for gestational age and
      to assess the agreement among the 3 imaging modalities. RESULTS: The number of
      fetuses in the study group was 193, 172, and 151 for 2D ultrasound, 3D
      ultrasound, and MR imaging, respectively. The mean and median gestational ages
      were 29.1 weeks, 29.5 weeks (range, 21-35 weeks); 28.2 weeks, 29.05 weeks (range,
      21-35 weeks); and 32.1 weeks, 32.6 weeks (range, 27-35 weeks) for 2D ultrasound,
      3D ultrasound, and MR imaging, respectively. In all 3 modalities, the biometric
      measurements of the vermis have shown a linear growth with gestational age. For
      all 4 biometric parameters, the lowest results were those measured by MR imaging,
      while the highest results were measured by 3D ultrasound. The inter- and
      intraobserver agreement was excellent for all measures and all imaging
      modalities. Limits of agreement were considered acceptable for clinical purposes
      for all parameters, with excellent or substantial agreement defined by the
      intraclass correlation coefficient. CONCLUSIONS: Imaging technique-specific
      reference data should be used for the assessment of the fetal vermis in
      pregnancy.

PMID- 27032975
TI  - MRI Appearance of Intracerebral Iodinated Contrast Agents: Is It Possible to
      Distinguish Extravasated Contrast Agent from Hemorrhage?
AB  - BACKGROUND AND PURPOSE: Hyperattenuated cerebral areas on postinterventional CT
      are a common finding after endovascular stroke treatment. There is uncertainty
      about the extent to which these hyperattenuated areas correspond to hemorrhage or
      contrast agent that extravasated into infarcted parenchyma during angiography. We
      evaluated whether it is possible to distinguish contrast extravasation from blood
      on MR imaging. MATERIALS AND METHODS: We examined the influence of iodinated
      contrast agents on T1, T2, and T2* and magnetic susceptibility in a phantom model
      and an ex vivo animal model. We determined T1, T2, and T2* relaxation times and
      magnetic susceptibility of iopamidol and iopromide in dilutions of 1:1; 1:2; 1:4;
      1:10; and 1:100 with physiologic saline solution. We then examined the appearance
      of intracerebral iopamidol on MR imaging in an ex vivo animal model. To this end,
      we injected iopamidol into the brain of a deceased swine. RESULTS: Iopamidol and
      iopromide cause a negative susceptibility shift and T1, T2, and T2* shortening.
      The effects, however, become very small in dilutions of 1:10 and higher.
      Undiluted iopamidol, injected directly into the brain parenchyma, did not cause
      visually distinctive signal changes on T1-weighted spin-echo, T2-weighted turbo
      spin-echo, and T2*-weighted gradient recalled-echo imaging. CONCLUSIONS: It is
      unlikely that iodinated contrast agents extravasated into infarcted brain
      parenchyma cause signal changes that mimic hemorrhage on T1WI, T2WI, and T2*WI.
      Our results imply that extravasated contrast agents can be distinguished from
      hemorrhage on MR imaging.

PMID- 27032976
TI  - The use of facial expressions for pain assessment purposes in dementia: a
      narrative review.
AB  - Facial expressions convey reliable nonverbal signals about pain and thus are very
      useful for assessing pain in patients with limited communicative ability, such as
      patients with dementia. In this review, we present an overview of the available
      pain observation tools and how they make use of facial expressions. Utility and
      reliability of facial expressions to measure pain in dementia are discussed,
      together with the effect of dementia severity on these facial expressions. Next,
      we present how behavioral alterations may overlap with facial expressions of
      pain, and may even influence the extent to which pain is facially expressed. The
      main focus is on disinhibition, apathy and emotional changes. Finally, an
      overview of theoretical considerations and practical implications is presented
      for assessing pain using facial expressions in clinical settings. 

PMID- 27032977
TI  - Fines for breaching NHS performance targets are "counterproductive".

PMID- 27032978
TI  - Extending the applicability of the Goldschmidt tolerance factor to arbitrary
      ionic compounds.
AB  - Crystal structure determination is essential for characterizing materials and
      their properties, and can be facilitated by various tools and indicators. For
      instance, the Goldschmidt tolerance factor (T) for perovskite compounds is
      acknowledged for evaluating crystal structures in terms of the ionic packing.
      However, its applicability is limited to perovskite compounds. Here, we report on
      extending the applicability of T to ionic compounds with arbitrary ionic
      arrangements and compositions. By focussing on the occupancy of constituent
      spherical ions in the crystal structure, we define the ionic filling fraction
      (IFF), which is obtained from the volumes of crystal structure and constituent
      ions. Ionic compounds, including perovskites, are arranged linearly by the IFF,
      providing consistent results with T. The linearity guides towards finding
      suitable unit cell and composition, thus tackling the main obstacle for
      determining new crystal structures. We demonstrate the utility of the IFF by
      solving the structure of three hydrides with new crystal structures. 

PMID- 27032979
TI  - Real-time high dynamic range laser scanning microscopy.
AB  - In conventional confocal/multiphoton fluorescence microscopy, images are
      typically acquired under ideal settings and after extensive optimization of
      parameters for a given structure or feature, often resulting in information loss
      from other image attributes. To overcome the problem of selective data display,
      we developed a new method that extends the imaging dynamic range in optical
      microscopy and improves the signal-to-noise ratio. Here we demonstrate how real
      time and sequential high dynamic range microscopy facilitates automated three
      dimensional neural segmentation. We address reconstruction and segmentation
      performance on samples with different size, anatomy and complexity. Finally, in
      vivo real-time high dynamic range imaging is also demonstrated, making the
      technique particularly relevant for longitudinal imaging in the presence of
      physiological motion and/or for quantification of in vivo fast tracer kinetics
      during functional imaging. 

PMID- 27032980
TI  - Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter.
AB  - The serotonin transporter (SERT) is an integral membrane protein that exploits
      preexisting sodium-, chloride-, and potassium ion gradients to catalyze the
      thermodynamically unfavorable movement of synaptic serotonin into the presynaptic
      neuron. SERT has garnered significant clinical attention partly because it is the
      target of multiple psychoactive agents, including the antidepressant paroxetine
      (Paxil), the most potent selective serotonin reuptake inhibitor known. However,
      the binding site and orientation of paroxetine in SERT remain controversial. To
      provide molecular insight, we constructed SERT homology models based on the
      Drosophila melanogaster dopamine transporter and docked paroxetine to these
      models. We tested the predicted binding configurations with a combination of
      radioligand binding and flux assays on wild-type and mutant SERTs. Our data
      suggest that the orientation of paroxetine, specifically its fluorophenyl ring,
      in SERT's substrate binding site directly depends on this pocket's charge
      distribution, and thereby provide an avenue toward understanding and enhancing
      high-affinity antidepressant activity. 

PMID- 27032983
TI  - Innovation: Sweat-sensing patch for glucose monitoring and drug delivery.

PMID- 27032981
TI  - Micronutrient deficiencies in pregnancy worldwide: health effects and prevention.
AB  - Micronutrients, vitamins and minerals accessible from the diet, are essential for
      biologic activity. Micronutrient status varies widely throughout pregnancy and
      across populations. Women in low-income countries often enter pregnancy
      malnourished, and the demands of gestation can exacerbate micronutrient
      deficiencies with health consequences for the fetus. Examples of efficacious
      single micronutrient interventions include folic acid to prevent neural tube
      defects, iodine to prevent cretinism, zinc to reduce risk of preterm birth, and
      iron to reduce the risk of low birth weight. Folic acid and vitamin D might also
      increase birth weight. While extensive mechanistic and association research links
      multiple antenatal micronutrients with plausible materno-fetal health advantages,
      hypothesized benefits have often been absent, minimal or unexpected in trials.
      These findings suggest a role for population context in determining health
      responses and filling extensive gaps in knowledge. Multiple micronutrient
      supplements reduce the risks of being born with low birth weight, small for
      gestational age or stillborn in undernourished settings, and justify
      micronutrient interventions with antenatal care. Measurable health effects of
      gestational micronutrient exposure might persist into childhood but few data
      exists on potential long-term benefits. In this Review, we discuss micronutrient
      intake recommendations, risks and consequences of deficiencies, and the effects
      of interventions with a particular emphasis on offspring. 

PMID- 27032984
TI  - Effects of Additional Intra-aortic Balloon Counter-Pulsation Therapy to
      Cardiogenic Shock Patients Supported by Extra-corporeal Membranous Oxygenation.
AB  - Extra-corporeal membranous oxygenation (ECMO) has been applied in patients with
      cardiopulmonary failure. One critical drawback of peripheral ECMO is an increase
      in left ventricular (LV) afterload which could be counterbalanced by the
      combination of intra-aortic balloon counter-pulsation (IABP) therapy. We
      hypothesized that an add-on therapy with IABP could improve outcomes in patients
      receiving ECMO support. We included patients (>18 years old) from 2002 to 2013
      requiring ECMO support due to cardiogenic shock in a medical center. A total of
      529 patients (227 ECMO alone and 302 combined IABP plus ECMO) were included. The
      mortality rates at 2 weeks (48.5 vs. 47.7%) after ECMO implantation were not
      different between the two groups (ECMO vs. combined group). After adjustment for
      propensity score and potential confounders, the odds ratios of outcomes within 14
      days (combined group vs. ECMO) for poor LV systolic function, high preload, multi
      organ failure and mortality were not different. The results remained similar for
      subgroup analysis. Compared with ECMO alone, combined IABP and ECMO treatment did
      not improve outcomes in patients with circulatory failure. 

PMID- 27032985
TI  - A morphospace for synthetic organs and organoids: the possible and the actual.
AB  - Efforts in evolutionary developmental biology have shed light on how organs are
      developed and why evolution has selected some structures instead of others. These
      advances in the understanding of organogenesis along with the most recent
      techniques of organotypic cultures, tissue bioprinting and synthetic biology
      provide the tools to hack the physical and genetic constraints in organ
      development, thus opening new avenues for research in the form of completely
      designed or merely altered settings. Here we propose a unifying framework that
      connects the concept of morphospace (i.e. the space of possible structures) with
      synthetic biology and tissue engineering. We aim for a synthesis that
      incorporates our understanding of both evolutionary and architectural constraints
      and can be used as a guide for exploring alternative design principles to build
      artificial organs and organoids. We present a three-dimensional morphospace
      incorporating three key features associated to organ and organoid complexity. The
      axes of this space include the degree of complexity introduced by developmental
      mechanisms required to build the structure, its potential to store and react to
      information and the underlying physical state. We suggest that a large fraction
      of this space is empty, and that the void might offer clues for alternative ways
      of designing and even inventing new organs. 

PMID- 27032986
TI  - A Customizable Model for Chronic Disease Coordination: Lessons Learned From the
      Coordinated Chronic Disease Program.
AB  - In 2012, the Centers for Disease Control and Prevention provided funding and
      technical assistance to all states and territories to implement the Coordinated
      Chronic Disease Program, marking the first time that all state health departments
      had federal resources to coordinate chronic disease prevention and control
      programs. This article describes lessons learned from this initiative and
      identifies key elements of a coordinated approach. We analyzed 80 programmatic
      documents from 21 states and conducted semistructured interviews with 7 chronic
      disease directors. Six overarching themes emerged: 1) focused agenda, 2)
      identification of functions, 3) comprehensive planning, 4) collaborative
      leadership and expertise, 5) managed resources, and 6) relationship building.
      These elements supported 4 essential activities: 1) evidence-based interventions,
      2) strategic use of staff, 3) consistent communication, and 4) strong program
      infrastructure. On the basis of these elements and activities, we propose a
      conceptual model that frames overarching concepts, skills, and strategies needed
      to coordinate state chronic disease prevention and control programs. 

PMID- 27032982
TI  - Late endocrine effects of childhood cancer.
AB  - The cure rate for paediatric malignancies is increasing, and most patients who
      have cancer during childhood survive and enter adulthood. Surveillance for late
      endocrine effects after childhood cancer is required to ensure early diagnosis
      and treatment and to optimize physical, cognitive and psychosocial health. The
      degree of risk of endocrine deficiency is related to the child's sex and their
      age at the time the tumour is diagnosed, as well as to tumour location and
      characteristics and the therapies used (surgery, chemotherapy or radiation
      therapy). Potential endocrine problems can include growth hormone deficiency,
      hypothyroidism (primary or central), adrenocorticotropin deficiency,
      hyperprolactinaemia, precocious puberty, hypogonadism (primary or central),
      altered fertility and/or sexual function, low BMD, the metabolic syndrome and
      hypothalamic obesity. Optimal endocrine care for survivors of childhood cancer
      should be delivered in a multidisciplinary setting, providing continuity from
      acute cancer treatment to long-term follow-up of late endocrine effects
      throughout the lifespan. Endocrine therapies are important to improve long-term
      quality of life for survivors of childhood cancer.

PMID- 27032987
TI  - Tailoring Care to Vulnerable Populations by Incorporating Social Determinants of
      Health: the Veterans Health Administration's "Homeless Patient Aligned Care Team"
      Program.
AB  - INTRODUCTION: Although the clinical consequences of homelessness are well
      described, less is known about the role for health care systems in improving
      clinical and social outcomes for the homeless. We described the national
      implementation of a "homeless medical home" initiative in the Veterans Health
      Administration (VHA) and correlated patient health outcomes with characteristics
      of high-performing sites. METHODS: We conducted an observational study of 33 VHA
      facilities with homeless medical homes and patient- aligned care teams that
      served more than 14,000 patients. We correlated site-specific health care
      performance data for the 3,543 homeless veterans enrolled in the program from
      October 2013 through March 2014, including those receiving ambulatory or acute
      health care services during the 6 months prior to enrollment in our study and 6
      months post-enrollment with corresponding survey data on the Homeless Patient
      Aligned Care Team (H-PACT) program implementation. We defined high performance as
      high rates of ambulatory care and reduced use of acute care services. RESULTS:
      More than 96% of VHA patients enrolled in these programs were concurrently
      receiving VHA homeless services. Of the 33 sites studied, 82% provided hygiene
      care (on-site showers, hygiene kits, and laundry), 76% provided transportation,
      and 55% had an on-site clothes pantry; 42% had a food pantry and provided on-site
      meals or other food assistance. Six-month patterns of acute-care use pre
      enrollment and post-enrollment for 3,543 consecutively enrolled patients showed a
      19.0% reduction in emergency department use and a 34.7% reduction in
      hospitalizations. Three features were significantly associated with high
      performance: 1) higher staffing ratios than other sites, 1) integration of social
      supports and social services into clinical care, and 3) outreach to and
      integration with community agencies. CONCLUSION: Integrating social determinants
      of health into clinical care can be effective for high-risk homeless veterans.

PMID- 27032988
TI  - Disparities in Health Insurance Coverage and Health Status Among Farmworkers,
      Sonoma County, California, 2013-2014.
AB  - INTRODUCTION: The Sonoma County Farmworker Health Survey (FHS) was conducted to
      describe the health and well-being of adult farmworkers in Sonoma County,
      California, and to identify preventable health disparities for this population.
      METHODS: From September 2013 through January 2014, venue-based and convenience
      sampling were used to survey 293 farmworkers aged 18 years or older. The
      questions included self-rated general health, diabetes and hypertension, and body
      mass index. To identify disparities between surveyed farmworkers and Sonoma
      County residents overall, age-adjusted prevalence estimates were developed by
      using indirect standardization to the adult (>=18 years) Sonoma County sample
      from the California Health Interview Survey for 2011-2012. RESULTS: Surveyed
      farmworkers were mostly male (91%) and Latino or Hispanic (95%), and 54% had an
      educational attainment of 8th grade or less. Most (81%) farmworkers reported
      their families earned less than $30,000 in 2012. After adjusting for age, 30% of
      farmworkers had US-based health insurance as compared with the 86% of Sonoma
      County adults in 2011-2012 (P < .001), and 15% of farmworkers reported ever being
      diagnosed with diabetes after adjusting for age as compared with 5% of Sonoma
      County adults (P = .002). After adjusting for age, 44% of farmworkers reported
      poor or fair health in general as compared with 13% of Sonoma County adults (P <
      .001). CONCLUSION: We identified significant health disparities between Sonoma
      County farmworkers and Sonoma County adults overall. Additional research and new
      health policies are necessary to eliminate these health disparities and to
      facilitate farmworker access to the health care system.

PMID- 27032989
TI  - Graphdiyne oxide as a platform for fluorescence sensing.
AB  - Graphdiyne (GD), a new kind of two-dimensional carbon allotrope consisting of a
      hexagonal ring and a diacetylenic linkage unit, is observed to exhibit a high
      fluorescence quenching ability and can be used as a new platform for fluorescence
      sensing, where GD oxide, the oxidized form of GD, is found to exhibit higher
      quenching ability than GD. As a proof-of-concept demonstration, GD oxide is used
      to establish a new platform for effective fluorescence sensing of DNA and
      thrombin with a high sensitivity and selectivity. 

PMID- 27032990
TI  - Optimising preterm nutrition: present and future.
AB  - The goal of preterm nutrition in achieving growth and body composition
      approximating that of the fetus of the same postmenstrual age is difficult to
      achieve. Current nutrition recommendations depend largely on expert opinion, due
      to lack of evidence, and are primarily birth weight based, with no consideration
      given to gestational age and/or need for catch-up growth. Assessment of growth is
      based predominately on anthropometry, which gives insufficient attention to the
      quality of growth. The present paper provides a review of the current literature
      on the nutritional management and assessment of growth in preterm infants. It
      explores several approaches that may be required to optimise nutrient intakes in
      preterm infants, such as personalising nutritional support, collection of
      nutrient intake data in real-time, and measurement of body composition. In
      clinical practice, the response to inappropriate nutrient intakes is delayed as
      the effects of under- or overnutrition are not immediate, and there is limited
      nutritional feedback at the cot-side. The accurate and non-invasive measurement
      of infant body composition, assessed by means of air displacement
      plethysmography, has been shown to be useful in assessing quality of growth. The
      development and implementation of personalised, responsive nutritional management
      of preterm infants, utilising real-time nutrient intake data collection, with
      ongoing nutritional assessments that include measurement of body composition is
      required to help meet the individual needs of preterm infants. 

PMID- 27032991
TI  - Biological antivirals for treatment of adenovirus infections.
AB  - Adenovirus (Ad) infections are usually mild and self-limiting, but severe
      systemic infections and fatal diseases can occur, especially in immunosuppressed
      patients. Anti-adenoviral pharmacotherapy has been proven to inhibit Ad
      infection, but its efficiency is limited. This review addresses biological
      antiviral agents as a new class of therapeutics for treatment of Ad infections.
      One group of agents is composed of short double-stranded RNA molecules that have
      been developed to inhibit Ad receptor and Ad protein expression. The second group
      of agents includes soluble virus receptor traps which inhibit Ad uptake into
      cells. Anti-Ad-adoptive T-cell therapy constitutes a third approach. We also
      outline how the combination of biological antiviral agents and combinations of
      these agents with the classical antiviral drugs can increase therapeutic
      efficiency in anti-adenoviral treatments.

PMID- 27032992
TI  - Tailoring Catalytic Activity of Pt Nanoparticles Encapsulated Inside Dendrimers
      by Tuning Nanoparticle Sizes with Subnanometer Accuracy for Sensitive
      Chemiluminescence-Based Analyses.
AB  - Here, we report the size-dependent catalysis of Pt dendrimer-encapsulated
      nanoparticles (DENs) having well-defined sizes over the range of 1-3 nm with
      subnanometer accuracy for the highly enhanced chemiluminescence of the
      luminol/H2O2 system. This size-dependent catalysis is ascribed to the differences
      in the chemical states of the Pt DENs as well as in their surface areas depending
      on their sizes. Facile and versatile applications of the Pt DENs in diverse
      oxidase-based assays are demonstrated as efficient catalysts for sensitive
      chemiluminescence-based analyses.

PMID- 27032993
TI  - [On the formation-process of the Atmospheric Sciences in the FRG since 1968].

PMID- 27032994
TI  - A simple technique to minimize needle displacement in gynecologic interstitial
      brachytherapy: Use of fully stretched elastic tapes.
AB  - PURPOSE: Previous studies on reproducibility in gynecologic high-dose-rate
      interstitial brachytherapy (HDRIB) have reported caudal needle displacements as
      high as 14-27.9 mm. The needle-template units in these studies were, however,
      sutured to the perineum, which gradually moved away from the target due to edema.
      To overcome the caudal force from the edema, we have been using fully stretched
      elastic tapes that exert cranial force on the template. To evaluate the
      effectiveness of our technique, caudal needle displacements relative to the
      target were investigated using CT coordinates. METHODS AND MATERIALS: Twenty-nine
      gynecologic cancer patients were treated using HDRIB. The template was pressed
      into the perineum using two elastic tapes. All patients underwent pretreatment
      and posttreatment CTs to obtain craniocaudal coordinates for the needles and the
      clinical target volume. RESULTS: The median displacements for the 533 needles
      relative to the clinical target volume were -0.8 mm (range, -5.7 to +4.7 mm).
      Absolute craniocaudal displacement >3 mm was observed in only 14.4% of the
      needles, with a maximum displacement of only 5.7 mm. CONCLUSIONS: The use of
      elastic tapes achieved smaller displacements compared to those in previous
      reports. This was a simple but effective technique to minimize needle
      displacement for gynecologic HDRIB.

PMID- 27032995
TI  - Rectal and bladder dose reduction with the addition of intravaginal balloons to
      vaginal packing in intracavitary brachytherapy for cervical cancer.
AB  - PURPOSE: The use of intravaginal Foley balloons in addition to conventional
      packing during high-dose-rate (HDR) tandem and ovoids intracavitary brachytherapy
      (ICBT) is a means to improve displacement of organs at risk, thus reducing dose
      dependent complications. The goal of this project was to determine the reduction
      in dose achieved to the bladder and rectum with intravaginal Foley balloons with
      CT-based planning and to share our packing technique. METHODS AND MATERIALS: One
      hundred and six HDR-ICBT procedures performed for 38 patients were analyzed for
      this report. An uninflated Foley balloon was inserted into the vagina above and
      below the tandem flange separately and secured in place with vaginal packing. CT
      images were then obtained with both inflated and deflated Foley balloons. Plan
      optimization occurred and dose volume histogram data were generated for the
      bladder and rectum. Maximum dose to 0.1, 1.0, and 2.0 cm(3) volumes for the
      rectum and bladder were analyzed and compared between inflated and deflated
      balloons using parametric statistical analysis. RESULTS: Inflation of
      intravaginal balloons allowed significant reduction of dose to the bladder and
      rectum. Amount of reduction was dependent on the anatomy of the patient and the
      placement of the balloons. Displacement of the organs at risk by the balloons
      allowed an average of 7.2% reduction in dose to the bladder (D0.1 cm(3)) and 9.3%
      to the rectum (D0.1 cm(3)) with a maximum reduction of 41% and 43%, respectively.
      CONCLUSIONS: For patients undergoing HDR-ICBT, a significant dose reduction to
      the bladder and rectum could be achieved with further displacement of these
      structures using intravaginal Foley balloons in addition to conventional vaginal
      packing.

PMID- 27032996
TI  - A systematic review of studies in the contributions of the work environment to
      ischaemic heart disease development.
AB  - BACKGROUND: There is need for an updated systematic review of associations
      between occupational exposures and ischaemic heart disease (IHD), using the GRADE
      system. METHODS:  INCLUSION CRITERIA: (i) publication in English in peer-reviewed
      journal between 1985 and 2014, (ii) quantified relationship between occupational
      exposure (psychosocial, organizational, physical and other ergonomic job factors)
      and IHD outcome, (iii) cohort studies with at least 1000 participants or
      comparable case-control studies with at least 50 + 50 participants, (iv)
      assessments of exposure and outcome at baseline as well as at follow-up and (v)
      gender and age analysis. Relevance and quality were assessed using predefined
      criteria. Level of evidence was then assessed using the GRADE system. Consistency
      of findings was examined for a number of confounders. Possible publication bias
      was discussed. RESULTS: Ninety-six articles of high or medium high scientific
      quality were finally included. There was moderately strong evidence (grade 3 out
      of 4) for a relationship between job strain and small decision latitude on one
      hand and IHD incidence on the other hand. Limited evidence (grade 2) was found
      for iso-strain, pressing work, effort-reward imbalance, low support, lack of
      justice, lack of skill discretion, insecure employment, night work, long working
      week and noise in relation to IHD. No difference between men and women with
      regard to the effect of adverse job conditions on IHD incidence. CONCLUSIONS:
      There is scientific evidence that employees, both men and women, who report
      specific occupational exposures, such as low decision latitude, job strain or
      noise, have an increased incidence of IHD.

PMID- 27032997
TI  - A dual-species microbial model for studying the dynamics between oral
      streptococci and periodontal pathogens during biofilm development on titanium
      surfaces by flow cytometry.
AB  - The association of the pioneer organisms Streptococcus mutans ATCC 25175 or
      Streptococcus oralis ATCC 9811 with secondary colonizers Fusobacterium nucleatum
      ATCC 25586 or Porphyromonas gingivalis ATCC 33277 during biofilm development on
      titanium surfaces was evaluated by flow cytometry (FCM) using specific polyclonal
      antibodies. ELISA and FCM were employed, revealing high antibody sensitivity and
      specificity. Biofilm formation of four dual-species combinations was analyzed by
      crystal violet staining, while the association between streptococci and
      periodontal pathogens was assessed using FCM. Dual-species association between S.
      oralis and P. gingivalis or F. nucleatum showed a proportional decrease in S.
      oralis during biofilm development, with a concomitant increase in P. gingivalis
      or F. nucleatum. This trend was not observed in either of the dual-species
      associations of S. mutans with the periodontal pathogens. Our dual-species
      microbial model, which employed FCM, proved to be useful in the study of
      partnerships between bacteria in oral associations, showing that the presence of
      primary colonizers is required for the establishment of secondary colonizers in
      biofilms. The proposed experimental approach is technically simple to prepare and
      analyze, and also proved to be reproducible; hence, it is well-suited for
      investigating the development and dynamics of oral communities. 

PMID- 27032998
TI  - [Prevalence of Hypertension and Associated Factors in Population Aged 16 to 90
      Years Old in Valencia Region, Spain].
AB  - OBJECTIVE: Hypertension is one of the main risk factor in terms of attributable
      mortality and the most common modifiable cardiovascular risk factor. The aim of
      the study was to estimate the prevalence of hypertension in population more than
      fifteen years of Valencia region and describe the strength of association between
      specific factors and the presence of hypertension. METHODS: Cross-sectional
      population-based study in 413 men and 415 women between 16 and 90 years
      participants in Nutrition Survey of Valencia held in 2010. Data were collected
      through household survey and blood pressure was measured using an automated
      sphygmomanometer. Hypertension was defined according to criteria established in
      2007 by the European Society of Hypertension and the European Society of
      Cardiology. Strength of association between hypertension and associated factors
      was measured by binary logistic regression for demographic explanatory variables,
      family history, lifestyle, anthropometric variables and others. RESULTS: The
      prevalence of hypertension estimated for Valencia region was 38,2% [95% CI 34,9
      to 41,5]; 40,7% in men [95% CI 35,0 to 45,5] and 35,7% in women [95% CI 31,1 to
      40,3]. Remained as associated variables with hypertension: age [45-64 years OR
      4.3, IC 95% 2.1-8.8; 65 or more years, OR 15.5, IC 95% 7.2-33.2], body mass index
      [overweight OR 2.1 95% CI 1.3 to 3.2; obesity OR 5.3, 95% CI 3.3 to 8.5] and
      diabetes [OR 2.4, 95% CI 1.2-4.8]. CONCLUSIONS: More than a third of the study
      population suffers from hypertension. Its risk increases with age. Overweight and
      diabetes mellitus double the likelihood of developing hypertension.

PMID- 27032999
TI  - GeneXpert assay for rapid detection of Mycobacterium tuberculosis complex in
      respiratory specimens from a high TB endemic area of Pakistan.
AB  - Tuberculosis is a global health problem, and its early diagnosis is the ultimate
      strategy for prevention and control. The current study was undertaken to evaluate
      conventional and molecular diagnostic assays for the detection of mycobacteria in
      pulmonary tuberculosis (TB) patients from Khyber Pakhtunkhwa region of Pakistan.
      A total of 259 clinically suspected patients of TB were processed for Zeihl
      Neelsen (ZN) microscopy, BACTEC MGIT liquid culture and GeneXpert assay. Among
      259 samples, 28 (10.81%) were positive for acid fast bacilli (AFB) on ZN
      microscopy. In liquid culture, the growth of mycobacterium species was obtained
      in 36 (13.89%) samples while the GeneXpert assay detected Mycobacterium
      tuberculosis (MTB) in 49 (18.91%) samples. Detection rate of MTB was
      significantly high (n = 49, p < 0.0095) on GeneXpert as compared to microscopy (n
      = 28); however no significant difference (p = 0.1230) was observed on GeneXpert
      (n = 49) and culture (n = 36) based detection of MTB. The strength of agreement
      between GeneXpert and microscopy was also poor (Kappa value < 0.114, 95% CI: 
      0.72 - 0.301) which support our results. MTB detection rate among female was high
      as compared to male TB patients while in age wise, the age group 55-64 years has
      almost high detection rate on microscopy, culture and GeneXpert assay. Findings
      of the present study highlighted that GeneXpert is more efficient tool for timely
      diagnosis and proper TB control in high TB endemic area. 

PMID- 27033000
TI  - Potentiation of antibiotic activity of aminoglycosides by natural products from
      Cordia verbenacea DC.
AB  - Medicinal plants are often the only therapeutic resource for many communities and
      ethnic groups. Cordia verbenacea DC., "Erva-baleeira," is one of the species of
      plants currently used to produce a phytotherapeutic product extracted from its
      leaves. The present study aimed to establish its chemical profile, antibacterial
      activity and resistance-modulating potential. The C. verbenacea extracts were
      prepared from fresh leaves using solvents as methanol and hexane. Ethyl Acetate
      was used for the preparation of the fraction. Phytochemical screening was carried
      out using HPLC-DAD for determination and quantification of the secondary
      metabolites present in the fractions. Antibacterial and resistance-modulation
      assays were performed to determine minimum inhibitory concentration (MIC) using a
      microdilution assay. The data were subjected to statistical analysis with two-way
      ANOVA and Bonferroni posttests. Results of phytochemical prospecting and HPLC
      analysis of the fractions were in agreement with the literature. The natural
      products presented moderate antibacterial activity when considering the clinical
      relevance of a MIC of 256 MUg/mL against Staphylococcus aureus, Escherichia coli
      and Pseudomonas aeruginosa, and 512 MUg/mL against P. aeruginosa. However, when
      the fractions were combined with antibiotics we observed a synergic effect, as
      natural products enhanced the antibacterial effect of aminoglycosides,
      significantly decreasing the MIC of antibiotics at 12.5%-98.4%. We believe that
      the data obtained from phytochemical analysis and from antibacterial and
      resistance modulation assays of C. verbenacea extracts new can open perspectives
      in the search for new alternatives for the treatment of bacterial infections and
      stimulate the renewed use of antibiotics with reduced effectiveness due to
      resistance. 

PMID- 27033001
TI  - Metabolic role of lactobacilli in weight modification in humans and animals.
AB  - Obesity represents a worldwide public health crisis. Trials suggested that
      intestinal microbiota may contribute to the development of obesity and
      highlighted the involvement of bacteria, including Lactobacillus spp., in changes
      to the host metabolism. Several experiments have shown significant effects of
      Lactobacillus probiotics on weight modification. Lactobacillus spp. are involved
      in the digestion of complex carbohydrates not digested by the host in the colon
      and also participate in the degradation of lipids and simple sugars in the
      duodenum and jejunum. Moreover, Lactobacillus species survive throughout the
      gastrointestinal tract, as they are able to survive in the presence of bile and
      low pH, and produce an antimicrobial agent, allowing them to reduce the number of
      bacteria in the gut. Hence, Lactobacillus spp. can have a significant impact on
      microbiota and, consequently, on weight change. Here, we review current studies
      of Lactobacillus spp. involved in weight change and discuss the different
      mechanisms of action by which Lactobacillus spp. acts on host digestion and
      appears to influence weight.

PMID- 27033002
TI  - Antidepressant-like effect of low dose ketamine and scopolamine co-treatment in
      mice.
AB  - Current medications for depression typically require weeks of treatment before
      significant clinical improvement is observed, and are only effective in a
      relatively small subset of patients. Recent human clinical studies have
      demonstrated that ketamine, an NMDA receptor antagonist, and scopolamine, a
      muscarinic acetylcholine receptor antagonist, produce rapid antidepressant
      responses within hours of administration, and are effective in treatment
      resistant patients. We hypothesize that efficacy and tolerability may be improved
      by combining lower doses of both drugs in the treatment of depression. We
      therefore conducted a preclinical study in mice to assess whether co-treatment of
      low doses of scopolamine and ketamine that alone are ineffective has
      antidepressant-like effects in the forced swim test (FST), an assay with
      predictive validity for antidepressant drugs. Whereas single administration of
      ketamine (3mg/kg intraperitoneal [i.p.]) or scopolamine (0.1mg/kg i.p.) did not
      reduce immobility time in the FST, co-administration of both drugs at these doses
      significantly reduced immobility time by 45% compared to vehicle treated
      controls. These results suggest that the combination of subeffective doses of
      ketamine and scopolamine may prove efficacious for the treatment of depression
      and should be evaluated in human clinical trials.

PMID- 27033003
TI  - The effect of explosive blast loading on human neuroblastoma cells.
AB  - Diagnosis of mild to moderate traumatic brain injury is challenging because brain
      tissue damage progresses slowly and is not readily detectable by conventional
      imaging techniques. We have developed a novel in vitro model to study primary
      blast loading on dissociated neurons using nitroamine explosives such as those
      used on the battlefield. Human neuroblastoma cells were exposed to single and
      triple 50-psi explosive blasts and single 100-psi blasts. Changes in membrane
      permeability and oxidative stress showed a significant increase for the single
      and triple 100-psi blast conditions compared with single 50-psi blast and
      controls.

PMID- 27033004
TI  - Separation of plasmid DNA topoisomers by multimodal chromatography.
AB  - The ability to analyze the distribution of topoisomers in a plasmid DNA sample is
      important when evaluating the quality of preparations intended for gene therapy
      and DNA vaccination or when performing biochemical studies on the action of
      topoisomerases and gyrases. Here, we describe the separation of supercoiled (sc)
      and open circular (oc) topoisomers by multimodal chromatography. A medium
      modified with the ligand N-benzyl-N-methyl ethanolamine and an elution scheme
      with increasing NaCl concentration are used to accomplish the baseline separation
      of sc and oc plasmid. The utility of the method is demonstrated by quantitating
      topoisomers in a purified plasmid sample.

PMID- 27033005
TI  - Cellometer image cytometry as a complementary tool to flow cytometry for
      verifying gated cell populations.
AB  - Traditionally, many cell-based assays that analyze cell populations and
      functionalities have been performed using flow cytometry. However, flow
      cytometers remain relatively expensive and require highly trained operators for
      routine maintenance and data analysis. Recently, an image cytometry system has
      been developed by Nexcelom Bioscience (Lawrence, MA, USA) for automated cell
      concentration and viability measurement using bright-field and fluorescent
      imaging methods. Image cytometry is analogous to flow cytometry in that gating
      operations can be performed on the cell population based on size and fluorescent
      intensity. In addition, the image cytometer is capable of capturing bright-field
      and fluorescent images, allowing for the measurement of cellular size and
      fluorescence intensity data. In this study, we labeled a population of cells with
      an enzymatic vitality stain (calcein-AM) and a cell viability dye (propidium
      iodide) and compared the data generated by flow and image cytometry. We report
      that measuring vitality and viability using the image cytometer is as effective
      as flow cytometric assays and allows for visual confirmation of the sample to
      exclude cellular debris. Image cytometry offers a direct method for performing
      fluorescent cell-based assays but also may be used as a complementary tool to
      flow cytometers for aiding the analysis of more complex samples.

PMID- 27033006
TI  - The utility of stable isotope labeled (SIL) analogues in the bioanalysis of
      endogenous compounds by LC-MS applied to the study of bile acids in a
      metabolomics assay.
AB  - The growing field of biomarker bioanalysis by liquid chromatography mass
      spectrometry (LC-MS) is challenged with the selection of suitable matrices to
      construct relevant and valid calibration curves resulting in not only precise but
      also accurate data. Because surrogate matrices are often employed with the
      associated concerns about the accuracy of the obtained data, here we present an
      assay using surrogate analytes in naive biological matrices. This approach is
      illustrated with the analysis of endogenous bile acids (e-BAs) in serum and
      plasma using stable isotope-labeled (SIL) analogues as calibration standards to
      address the matrix concerns. Several deuterated BAs (d-BAs) were used as
      standards representing respectively grouped e-BAs with structural similarity
      allowing for the simultaneous bioanalysis of 16 e-BA. The utility of this LC-MS
      assay employing d-BAs is demonstrated with the analysis of samples resultant of a
      controlled metabolomics study where a cohort of rats was fed/fasted to
      investigate the change of e-BAs dependent on food consumption and fasting time.

PMID- 27033008
TI  - Analysis of the length distribution of amyloid fibrils by centrifugal
      sedimentation.
AB  - The aggregation of normally soluble peptides and proteins into amyloid fibrils is
      a process associated with a wide range of pathological conditions, including
      Alzheimer's and Parkinson's diseases. It has become apparent that aggregates of
      different sizes possess markedly different biological effects, with aggregates of
      lower relative molecular weight being associated with stronger neurotoxicity.
      Yet, although many approaches exist to measure the total mass concentration of
      aggregates, the ability to probe the length distribution of growing aggregates in
      solution has remained more elusive. In this work, we applied a differential
      centrifugation technique to measure the sedimentation coefficients of amyloid
      fibrils produced during the aggregation process of the amyloid beta (M1-42)
      peptide (Abeta42). The centrifugal method has the advantage of providing
      structural information on the fibril distribution directly in solution and
      affording a short analysis time with respect to alternative imaging and
      analytical centrifugation approaches. We show that under quiescent conditions
      interactions between Abeta42 fibrils lead to lateral association and to the
      formation of entangled clusters. By contrast, aggregation under shaking generates
      a population of filaments characterized by shorter lengths. The results, which
      have been validated by cryogenic transmission electron microscopy (cryo-TEM)
      analysis, highlight the important role that fibril-fibril assembly can play in
      the deposition of aggregation-prone peptides.

PMID- 27033007
TI  - Surface plasmon resonance biosensor assay for the analysis of small-molecule
      inhibitor binding to human and parasitic phosphodiesterases.
AB  - In the past decade, surface plasmon resonance (SPR) biosensor-based technology
      has been exploited more and more to characterize the interaction between drug
      targets and small-molecule modulators. Here, we report the successful application
      of SPR methodology for the analysis of small-molecule binding to two
      therapeutically relevant cAMP phosphodiesterases (PDEs), Trypanosoma brucei PDEB1
      which is implicated in African sleeping sickness and human PDE4D which is
      implicated in a plethora of disease conditions including inflammatory pulmonary
      disorders such as asthma, chronic obstructive pulmonary disease and central
      nervous system (CNS) disorders. A protocol combining the use of directed capture
      using His-tagged PDE_CDs with covalent attachment to the SPR surface was
      developed. This methodology allows the determination of the binding kinetics of
      small-molecule PDE inhibitors and also allows testing their specificity for the
      two PDEs. The SPR-based assay could serve as a technology platform for the
      development of highly specific and high-affinity PDE inhibitors, accelerating
      drug discovery processes.

PMID- 27033009
TI  - A new formula to calculate activity of superoxide dismutase in indirect assays.
AB  - To calculate superoxide dismutase (SOD) activity rapidly and accurately by
      indirect SOD assays, a formula based on the ratio of the catalytic speed of SOD
      to the reaction speed of the indicator with superoxide anion was deduced. The
      accuracy of this formula was compared with the conventional formula based on
      inhibition in five indirect SOD assays. The new formula was validated in nearly
      the entire SOD activity range, whereas the conventional formula was validated
      only during inhibition of 40-60%. This formula might also be used for the assays
      of other enzymes. 

PMID- 27033010
TI  - Successful treatment with anti-TNF-alpha antibody for localised lipodystrophy.

PMID- 27033011
TI  - Audio-visual integration effect in lateral occipital cortex during an object
      recognition task: An interference pilot study.
AB  - BACKGROUND: Recent neuroimaging data support the hypothesis of a multisensory
      interplay at low-level sensory-specific cortex. OBJECTIVE: We used an on-line
      interference approach by rTMS to investigate the role of the left lateral
      occipital cortex (LOC) in audio-visual (AV) object recognition process. METHODS:
      Fifteen healthy volunteers performed a visual identification task of degraded
      pictures presented alone or simultaneously to coherent or non-coherent sounds.
      Focal 10-Hz rTMS at an intensity of 100% resting motor threshold was delivered
      simultaneously to the picture. Two blocks of 60 pictures were randomly displayed
      in two different experimental conditions: rTMS of the left LOC and over Cz.
      RESULTS: rTMS of the left LOC produced a worsening of the accuracy compared to
      rTMS over Cz specifically in the coherent AV condition. CONCLUSION: These data
      support the view that audio-visual interaction effect may occur at early stage of
      recognition processing.

PMID- 27033012
TI  - Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant
      Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02).
AB  - BACKGROUND: Various brain stimulation techniques are in use to treat epilepsy.
      These methods usually require surgical implantation procedures. Transcutaneous
      vagus nerve stimulation (tVNS) is a non-invasive technique to stimulate the left
      auricular branch of the vagus nerve at the ear conch. OBJECTIVE: We performed a
      randomized, double-blind controlled trial (cMPsE02) to assess efficacy and safety
      of tVNS vs. control stimulation in patients with drug-resistant epilepsy.
      METHODS: Primary objective was to demonstrate superiority of add-on therapy with
      tVNS (stimulation frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37)
      in reducing seizure frequency over 20 weeks. Secondary objectives comprised
      reduction in seizure frequency from baseline to end of treatment, subgroup
      analyses and safety evaluation. RESULTS: Treatment adherence was 84% in the 1 Hz
      group and 88% in the 25 Hz group, respectively. Stimulation intensity
      significantly differed between the 1 Hz group (1.02 +/- 0.83 mA) and the 25 Hz
      group (0.50 +/- 0.47 mA; p = 0.006). Mean seizure reduction per 28 days at end of
      treatment was -2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146).
      In contrast to controls, we found a significant reduction in seizure frequency in
      patients of the 25 Hz group who completed the full treatment period (20 weeks; n
      = 26, 34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups.
      Subgroup analyses for seizure type and baseline seizure frequency revealed no
      significant differences. Adverse events were usually mild or moderate and
      comprised headache, ear pain, application site erythema, vertigo, fatigue, and
      nausea. Four serious adverse events were reported including one sudden
      unexplained death in epilepsy patients (SUDEP) in the 1 Hz group which was
      assessed as not treatment-related. CONCLUSIONS: tVNS had a high treatment
      adherence and was well tolerated. Superiority of 25 Hz tVNS over 1 Hz tVNS could
      not be proven in this relatively small study, which might be attributed to the
      higher stimulation intensity in the control group. Efficacy data revealed results
      that justify further trials with larger patient numbers and longer observation
      periods.

PMID- 27033013
TI  - Exogenous RNA interference exposes contrasting roles for sugar exudation in host
      finding by plant pathogens.
AB  - Plant parasitic nematodes (PPN) locate host plants by following concentration
      gradients of root exudate chemicals in the soil. We present a simple method for
      RNA interference (RNAi)-induced knockdown of genes in tomato seedling roots,
      facilitating the study of root exudate composition, and PPN responses. Knockdown
      of sugar transporter genes, STP1 and STP2, in tomato seedlings triggered
      corresponding reductions of glucose and fructose, but not xylose, in collected
      root exudate. This corresponded directly with reduced infectivity and stylet
      thrusting of the promiscuous PPN Meloidogyne incognita, however we observed no
      impact on the infectivity or stylet thrusting of the selective Solanaceae PPN
      Globodera pallida. This approach can underpin future efforts to understand the
      early stages of plant-pathogen interactions in tomato and potentially other crop
      plants.

PMID- 27033014
TI  - Deficient aversive-potentiated startle and the triarchic model of psychopathy:
      The role of boldness.
AB  - This study examined the contribution of the phenotypic domains of boldness,
      meanness, and disinhibition of the triarchic conceptualization of psychopathy
      (Patrick, Fowles, & Krueger, 2009) to deficient aversive-potentiated startle in a
      mixed-gender sample of 180 undergraduates. Eyeblink responses to noise probes
      were recorded during a passive picture-viewing task (erotica, neutral, threat,
      and mutilation). Deficient threat vs. neutral potentiation was uniquely related
      to increased boldness scores, thus suggesting that the diminished defensive
      reaction to aversive stimulation is specifically linked to the charm, social
      potency and venturesomeness features of psychopathy (boldness), but not to
      features such as callousness, coldheartedness and cruelty traits (meanness), even
      though both phenotypes theoretically share the same underlying low-fear
      disposition. Our findings provide further evidence of the differential
      association between distinct psychopathy components and deficits in defensive
      reactivity and strongly support the validity of the triarchic model of
      psychopathy in disentangling the etiology of this personality disorder.

PMID- 27033015
TI  - Targeting frequent users of emergency departments: Prominent risk factors and
      policy implications.
AB  - This study investigates the characteristics of frequent users of accident and
      emergency departments (AEDs) and recommends alternative medical services for such
      patients. Prominent demographic and clinical risk factors for individuals
      accessing seven AEDs located in the metropolitan area of Genoa, Italy are
      identified and analysed. A truncated count data model is implemented to establish
      the determinants of access, while a multinomial logistic regression is used to
      highlight potential differences among different user categories. According to
      previous studies, empirical findings suggest that despite the relevance of
      demographic drivers, vulnerability conditions (e.g. abuse of alcohol and drugs,
      chronic conditions, and psychological distress) are the main reasons behind
      frequent AED use; the analysis seems to confirm an association between AED
      frequent use and lower level of urgency. Since frequent and highly frequent users
      are found responsible for disproportionate resource absorption with respect to
      total amount of AED costs (they represent roughly 10% of the total number of
      patients, but contribute to more than 19% of the total annual AED cost), policies
      aiming to reduce frequent use of AEDs could bring significant savings in economic
      resources. Thus, efficient actions could be oriented toward extending primary
      care services outside AED and toward instituting local aid services specifically
      addressed to people under the influence of substances or in conditions of mental
      distress. 

PMID- 27033016
TI  - Cardiopulmonary Exercise Tests in Patients With Heart Failure and Chronic
      Obstructive Pulmonary Disease: Moving Beyond Risk Assessment.

PMID- 27033017
TI  - Gait Speed: Stepping Towards Improved Assessment of Heart Failure Patients.

PMID- 27033019
TI  - Why Negative Trials Are Positive for Heart Failure Patients.

PMID- 27033018
TI  - 3D Printing to Guide Ventricular Assist Device Placement in Adults With
      Congenital Heart Disease and Heart Failure.
AB  - As the population of adults with congenital heart disease continues to grow, so
      does the number of these patients with heart failure. Ventricular assist devices
      are underutilized in adults with congenital heart disease due to their complex
      anatomic arrangements and physiology. Advanced imaging techniques that may
      increase the utilization of mechanical circulatory support in this population
      must be explored. Three-dimensional printing offers individualized structural
      models that would enable pre-surgical planning of cannula and device placement in
      adults with congenital cardiac disease and heart failure who are candidates for
      such therapies. We present a review of relevant cardiac anomalies, cases in which
      such models could be utilized, and some background on the cost and procedure
      associated with this process. 

PMID- 27033020
TI  - Reply: The AVOID-HF Trial: Points to Consider.

PMID- 27033021
TI  - The AVOID-HF Trial: Points to Consider.

PMID- 27033022
TI  - Prolonged controlled mechanical ventilation in humans triggers myofibrillar
      contractile dysfunction and myofilament protein loss in the diaphragm.
AB  - BACKGROUND: Prolonged controlled mechanical ventilation (CMV) in humans and
      experimental animals results in diaphragm fibre atrophy and injury. In animals,
      prolonged CMV also triggers significant declines in diaphragm myofibril
      contractility. In humans, the impact of prolonged CMV on myofibril contractility
      remains unknown. The objective of this study was to evaluate the effects of
      prolonged CMV on active and passive human diaphragm myofibrillar force generation
      and myofilament protein levels. METHODS AND RESULTS: Diaphragm biopsies were
      obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain
      dead organ donors (CMV group). Subjects in each group had been mechanically
      ventilated for 2-4 and 12-74 h, respectively. Specific force generation of
      diaphragm myofibrils was measured with atomic force cantilevers. Rates of force
      development (Kact), force redevelopment after a shortening protocol (Ktr) and
      relaxation (Krel) in fully activated myofibrils (pCa(2+)=4.5) were calculated to
      assess myosin cross-bridge kinetics. Myofilament protein levels were measured
      with immunoblotting and specific antibodies. Prolonged CMV significantly
      decreased active and passive diaphragm myofibrillar force generation, Kact, Ktr
      and Krel. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T,
      tropomyosin and titin protein levels significantly decreased in response to
      prolonged CMV, but no effects on alpha-actin, alpha-actinin or nebulin levels
      were observed. CONCLUSIONS: Prolonged CMV in humans triggers significant
      decreases in active and passive diaphragm myofibrillar force generation. This
      response is mediated, in part, by impaired myosin cross-bridge kinetics and
      decreased myofibrillar protein levels.

PMID- 27033023
TI  - Lesson of the month: selective use of cyclophosphamide in pregnancy for severe
      autoimmune respiratory disease.
AB  - We present the cases of two pregnant women who developed severe respiratory
      compromise in mid pregnancy, one due to rapidly progressive interstitial lung
      disease associated with mixed connective tissue disease and one secondary to
      diffuse alveolar haemorrhage due to antiglomerular basement membrane disease.
      Both were treated with high-dose steroids followed by pulsed intravenous
      cyclophosphamide. Both women went onto have live births although one baby was
      growth restricted and preterm. Neither baby had any evidence of congenital
      abnormalities.

PMID- 27033024
TI  - Neglect of Postoperative Pain Management in Children: A Qualitative Study Based
      on the Experiences of Parents.
AB  - Identifying parents' experiences of barriers to optimal postoperative pain
      management in children. DESIGN AND METHODS: This qualitative-content analysis
      study was conducted with 16 parents whose school-age children had undergone
      emergency abdominal surgery in university hospitals of Ahvaz, southern Iran. A
      purposive sampling method was used to select the participants. The semi
      structured interviews with all of the participants were recorded, transcribed,
      and analysed. RESULTS: After data analysis, neglect emerged as the main theme.
      This neglect consisted of three categories including the healthcare system's
      disregard, insufficient sensitivity of the healthcare providers, and hesitance or
      delays of parents and children in asking for care. CONCLUSION: The optimal
      management of children's postoperative pain requires the provision of relevant
      infrastructures by the healthcare system, responsible performance of the health
      professionals beyond the routine, and active and informed participation of both
      parents and children.

PMID- 27033025
TI  - A post hoc analysis of saxagliptin efficacy and safety in patients with type 2
      diabetes stratified by UKPDS 10-year cardiovascular risk score.
AB  - BACKGROUND AND AIMS: To assess the efficacy and safety of saxagliptin 2.5 and 5
      mg/d in patients with type 2 diabetes mellitus (T2DM) and high risk of coronary
      heart disease (CHD) or stroke as estimated by the United Kingdom Prospective
      Diabetes Study (UKPDS) risk engine. METHODS AND RESULTS: Post hoc analysis of
      data pooled from 5 previously reported phase 3, randomized, placebo-controlled,
      24-week studies was conducted. Patients were stratified into subgroups by UKPDS
      10-year CHD and/or stroke risk >=20% and CHD and stroke risk <20%. End points
      were adjusted mean change from baseline in glycated hemoglobin (HbA1c), fasting
      plasma glucose (FPG), 120-min postprandial glucose (PPG), and body weight and the
      proportion of patients achieving HbA1c <7% and <=8% at week 24. Pooled safety
      data were analyzed for adverse events (AEs) and hypoglycemia. Both doses of
      saxagliptin reduced HbA1c, FPG, and PPG to a greater extent than placebo
      regardless of UKPDS risk score. The proportions of patients achieving HbA1c <7%
      and <=8% were greater with saxagliptin than placebo and consistent across risk
      score groups. AE profile and hypoglycemia incidence were similar for saxagliptin
      and placebo across UKPDS risk score groups. CONCLUSION: Saxagliptin was well
      tolerated and improved glycemic control in patients with T2DM regardless of their
      CHD and stroke UKPDS risk score. Clinical trial registration numbers:
      Clinicaltrials.gov NCT00121641, NCT00316082, NCT00121667, NCT00313313, and
      NCT00295633.

PMID- 27033027
TI  - Excision of anomalous muscle bundles as an important addition to extended septal
      myectomy for treatment of left ventricular outflow tract obstruction.
AB  - OBJECTIVE: This study aims to report our preliminary experience and anatomic
      findings in the surgical treatment and postoperative management of hypertrophic
      obstructive cardiomyopathy. METHODS: This study included 277 patients with
      hypertrophic obstructive cardiomyopathy (168 [60.65%] were male), with a median
      age of 47 years (interquartile range, 35-54 years), who underwent surgical
      myectomy performed by 1 surgeon in Fuwai Hospital between May 2010 and April
      2015. The median follow-up was 14 months (interquartile range, 7-24 months).
      RESULTS: A total of 127 patients (45.85%) underwent concomitant procedures, and 2
      patients (0.72%) died in the early perioperative days. The left ventricular
      outflow gradient decreased from 78 mm Hg (interquartile range, 61-100 mm Hg) to
      11 mm Hg (interquartile range, 8-15 mm Hg) when discharged (P < .001). Of the 228
      patients with well-documented anatomic description, more than 80% had various
      intraventricular anomalies. The cumulative survival was 99.28% (95% confidence
      interval, 97.15-99.82) at 1 year and 96.98% (95% confidence interval, 92.56
      98.79) at 5 years. Of the surviving 272 patients, 268 (98.53%) were categorized
      with functional class I and II of the New York Heart Association classification
      at the latest evaluation. CONCLUSIONS: Anomalous muscle bundles are common in
      hypertrophic obstructive cardiomyopathy, and they may lead to middle-apical
      obstruction. Surgical myectomy provides excellent clinical outcomes with low risk
      for sufficient relief of obstruction and radical correction of intraventricular
      anomalies in patients with hypertrophic obstructive cardiomyopathy.

PMID- 27033028
TI  - Assessment of breast absorbed doses during thoracic computed tomography scan to
      evaluate the effectiveness of bismuth shielding.
AB  - During a lung computed tomography (CT) examination, breast and nearby
      radiosensitive organs are unnecessarily irradiated because they are in the path
      of the primary beam. The purpose of this paper is to determine the absorbed dose
      in breast and nearby organs for unshielded and shielded exposures with bismuth.
      The experiment was done with a female anthropomorphic phantom undergoing a
      typical thoracic CT scan, with TLD-100 thermoluminescent detectors insert at
      breast, lung and thyroid positions. Results showed that dose reduction due to
      bismuth shielding was approximately 30% and 50% for breast and thyroid,
      respectively; however, the influence of the bismuth on the image quality needs to
      be considered.

PMID- 27033026
TI  - Beneficial effects of omega-3 and vitamin E coadministration on gene expression
      of SIRT1 and PGC1alpha and serum antioxidant enzymes in patients with coronary
      artery disease.
AB  - BACKGROUND AND AIM: SIRT1 and PGC1alpha are two important genes, which play
      critical roles in regulating oxidative stress and inflammation processes. The
      study aimed assess the effects of coadministration of omega-3 and vitamin E
      supplements on SIRT1 and PGC1alpha gene expression and serum levels of
      antioxidant enzymes in coronary artery disease (CAD) patients. METHODS AND
      RESULTS: Participants of this randomized controlled trial included 60 CAD male
      patients who were categorized into three groups: Group 1 received omega-3 (4
      g/day) and vitamin E placebo (OP), group 2 omega-3 (4 g/day) and vitamin E (400
      IU/day; OE), and group 3 omega-3 and vitamin E placebos (PP) for 2 months. Gene
      expression of SIRT1 and PGC1alpha in peripheral blood mononuclear cells (PBMCS)
      was assessed by reverse transcription polymerase chain reaction (RT-PCR).
      Furthermore, serum antioxidant enzyme and high-sensitivity C-reactive protein
      (hsCRP) levels were assessed at the beginning and end of the intervention. Gene
      expression of SIRT1 and PGC1alpha increased significantly in the OE group (P =
      0.039 and P = 0.050, respectively). Catalase and hsCRP levels increased
      significantly in the OE and OP groups. However, glutathione peroxidase (GPX) and
      superoxide dismutase (SOD) levels did not statistically change in all groups. The
      total antioxidant capacity (TAC) increased significantly in the OE group (P =
      0.009) but not in OP and PP groups. CONCLUSION: Supplementation of omega-3 fatty
      acids in combination with vitamin E may have beneficial effects on CAD patients
      by increasing gene expression of SIRT1 and PGC1alpha and improving oxidative
      stress and inflammation in these patients.

PMID- 27033029
TI  - Continuous in vivo culture and indirect fluorescent antibody test for zoonotic
      protozoa of Babesia microti.
AB  - Babesiosis has attracted attention as a zoonotic disease. The disease is caused
      in immunocompetent individuals almost solely by Babesia microti, a rodent
      babesia. Most cases of human babesiosis by B. microti have been reported in the
      endemic foci of the Northeastern coastal areas and upper Midwest regions of the
      United States, while some sporadic cases have recently been reported in several
      Asian countries including Japan. Our previous surveys identified that four small
      subunit ribosomal RNA gene (SSUrDNA) types of B. microti parasitize Japanese
      rodents. Indirect fluorescent antibody test (IFAT) is often performed for the
      diagnosis of babesiosis together with microscopical examination of thin blood
      smears and PCR. We established IFAT against four SSUrDNA-types of B. microti
      using erythrocytes of SCID mice or Syrian hamsters infected with each SSUrDNA
      type B. microti. The results of IFAT for sera of ICR mice or Syrian hamsters
      infected with each SSUrDNA-type B. microti demonstrated that the four SSUrDNA
      types of B. microti have different serotypes. Here, we report technical or
      practical procedures of IFAT, which gains sufficiently stable results, including
      procedures of continuous in vivo culture of B. microti.

PMID- 27033030
TI  - Hormonal changes following a low-salt diet in patients with Meniere's disease.
AB  - OBJECTIVE: A low-salt diet has been the main treatment modality for Meniere's
      disease (MD) since the 1930s, although the mechanisms behind this therapy have
      not yet been elucidated. Salt reduction is associated with a physiological
      increase in plasma aldosterone concentration. Several experimental reports have
      suggested that aldosterone may increase endolymph absorption in the inner ear,
      particularly in the endolymphatic sac. Therefore, aldosterone elevations due to a
      low-salt diet may increase endolymph absorption in the endolymphatic sac. In this
      study, urinary sodium excretion, plasma aldosterone, and other hormones were
      measured during low-salt diet therapy in patients with MD. METHODS: We included
      13 patients with unilateral definite MD diagnosed at the Kagawa University
      Hospital. A national registered dietitian provided nutritional guidance initially
      for 14 enrolled patients with MD and prescribed them a low-salt diet (2g Na/day).
      Twenty-four hour urine was sampled at baseline, at 2, 4, 6, and 8 weeks, and at
      6, 12, 18, and 24 months after initiating the low-salt diet. Urine osmotic
      pressure, and Na, K, and Cl levels were measured, and 24-h urinary Na, K, and Cl
      excretion was estimated. Aldosterone, cortisol, hormones (including anti-diuretic
      hormone), Na, K, and Cl in the blood were measured, alongside plasma osmotic
      pressure. A total of 13 patients followed the low salt diet therapy for more than
      2 years, while one patient dropped out. RESULTS: Group 1 (n=7) included patients
      with a mean urinary sodium excretion amount lower than 3g/day and Group 2 (n=6)
      included those with more than 3g/day. Vertiginous states of all Group 1 patients
      comprised complete control (Class A, 100%), while Group 2 patients included Class
      A (four patients, 66%), Class C (one patient, 17%), and Class D (one patients,
      17%). Plasma aldosterone concentrations significantly increased during the 2-year
      low-salt diet; concentrations in Group 1 tended to be higher than that in Group
      2. Hearing improvements after 2 years in Group 1 were significantly better than
      that in Group 2. The plasma concentration of the hormones except aldosterone was
      not significantly changed during 2-year low-salt diet. CONCLUSION: A low-salt
      diet was an effective treatment for patients with Meniere's disease. This
      treatment will have a greater effect, when sodium intake is reduced to less than
      3g/day. A low-salt diet may induce an increase in the plasma aldosterone
      concentration that can activate ion transport and absorbing endolymph in the
      endolymphatic sac.

PMID- 27033031
TI  - Plant fluid proteomics: Delving into the xylem sap, phloem sap and apoplastic
      fluid proteomes.
AB  - The phloem sap, xylem sap and apoplastic fluid play key roles in long and short
      distance transport of signals and nutrients, and act as a barrier against local
      and systemic pathogen infection. Among other components, these plant fluids
      contain proteins which are likely to be important players in their
      functionalities. However, detailed information about their proteomes is only
      starting to arise due to the difficulties inherent to the collection methods.
      This review compiles the proteomic information available to date in these three
      plant fluids, and compares the proteomes obtained in different plant species in
      order to shed light into conserved functions in each plant fluid. Inter-species
      comparisons indicate that all these fluids contain the protein machinery for self
      maintenance and defense, including proteins related to cell wall metabolism,
      pathogen defense, proteolysis, and redox response. These analyses also revealed
      that proteins may play more relevant roles in signaling in the phloem sap and
      apoplastic fluid than in the xylem sap. A comparison of the proteomes of the
      three fluids indicates that although functional categories are somewhat similar,
      proteins involved are likely to be fluid-specific, except for a small group of
      proteins present in the three fluids, which may have a universal role, especially
      in cell wall maintenance and defense. This article is part of a Special Issue
      entitled: Plant Proteomics--a bridge between fundamental processes and crop
      production, edited by Dr. Hans-Peter Mock.

PMID- 27033032
TI  - The secretion, synthesis, and metabolism of cortisol and its downstream genes in
      the H-P-I axis of rare minnows (Gobiocypris rarus) are disrupted by acute
      waterborne cadmium exposure.
AB  - The H (hypothalamic)-P (pituitary)-I (interrenal) axis plays a critical role in
      the fish stress response and is regulated by several factors. Cadmium (Cd) is one
      of the most toxic heavy metals in the world, but its effects on the H-P-I axis of
      teleosts are largely unknown. Using rare minnow (Gobiocypris rarus) as an
      experimental animal, we found that Cd only disrupted the secretion and synthesis
      of cortisol. Neither hormones at the H or P level nor the expressions of their
      receptor genes (corticotropin-releasing hormone receptor (CRHR) and melanocortin
      receptor 2 (MC2R)) were affected. Steroidogenic acute regulator (StAR), CYP11A1
      and CYP11B1, which encode the key enzymes in the cortisol synthesis pathway, were
      significantly up-regulated in the kidney (including the head kidney). The level
      of 11beta-HSD2, which is required for the conversion of cortisol to cortisone,
      was increased in the kidney, intestine, brain, and hepatopancreas, whereas the
      expression of 11beta-HSD1, which encodes the reverse conversion enzyme, was
      increased in the gill, kidney and almost unchanged in other tissues. The enzyme
      activity concentration of 11beta-HSD2 was increased in the kidney as well. The
      level of glucocorticoid receptor (GR) decreased in the intestine, gill and
      muscle, and the key GR regulator FK506 binding protein5 (FKBP5) was up-regulated
      in the GR-decreased tissues, whereas the level of nuclear receptor co-repressor 1
      (NCoR1), another GR regulator remained almost unchanged. Thus, GR, FKBP5 and
      11beta-HSD2 may be involved in Cd-induced cortisol disruption. 

PMID- 27033033
TI  - Thermal emissivity of avian eggshells.
AB  - The hypothesis has been tested that evolution has resulted in lower thermal
      emissivity of eggs of birds breeding openly in cold climates than of eggs of
      birds that nest under protective covering or in warmer climates. Directional
      thermal emissivity has been estimated from directional-hemispherical reflectance
      spectra. Due to several methodological difficulties the absolute emissivity is
      not accurately determined, but differences between species are obvious. Most
      notably, small waders of the genus Calidris, breeding in cold climates on the
      tundra, and in most cases with uniparental nest attendance, have low directional
      emissivity of their eggshells, about 0.92 when integration is carried out for
      wavelengths up to 16MUm. Species belonging to Galloanserinae have the highest
      directional emissivity, about 0.96, of their eggs. No differences due to climate
      or breeding conditions were found within this group. Eggs of most other birds
      tested possess intermediate emissivity, but the values for Pica pica and Corvus
      corone cornix are as low as for Calidris. Large species-dependent differences in
      spectral reflectance were found at specific wavelengths. For instance, at
      4.259MUm the directional-hemispherical reflectance for galliforms range from 0.05
      to 0.09, while for Fratercula arctica and Fulmarus glacialis it is about 0.3. The
      reflection peaks at 6.5 and 11.3MUm due to calcite are differentially attenuated
      in different species. In conclusion, the hypothesis that evolution has resulted
      in lower thermal emissivity of bird eggs being exposed in cold climates is not
      supported by our results. The emissivity is not clearly related to nesting habits
      or climate, and it is unlikely that the small differences observed are
      ecologically important. The spectral differences between eggs that nevertheless
      exist should be taken into account when using infrared thermometers for
      estimating the surface temperature of avian eggs. 

PMID- 27033034
TI  - Temperature requirements for seed germination of Pereskia aculeata and Pereskia
      grandifolia.
AB  - Pereskia aculeata and Pereskia grandifolia have been studied widely due to their
      high nutritional and therapeutic values. However, little is known about the
      biological requirements of their seeds for the various germination factors. Thus,
      this experiment aimed to evaluate the thermal effects on the germination of these
      species at the temperatures of 24 degrees C, 27 degrees C, 30 degrees C, 33
      degrees C and 36 degrees C. After verification of the existence of differences in
      the performance of germination, a non-linear regression was carried out, relating
      the germination to temperature and identifying its point of maximum efficiency.
      We found that the lowest synchronization indexes of germination were observed
      close to 30 degrees C. The best germination response of the P. aculeata and P.
      grandifolia was observed at 30 degrees C and 33 degrees C, respectively, with
      greater germination strength and fewer days to attain 63.21% of germinations. The
      results obtained from the germination of P. aculeata and P. grandifolia can be
      described by the Weindull distribution model with three parameters, as proposed
      by Carneiro and Guedes (1992). 

PMID- 27033035
TI  - The effects of increased constant incubation temperature and cumulative acute
      heat shock exposures on morphology and survival of Lake Whitefish (Coregonus
      clupeaformis) embryos.
AB  - Increasing incubation temperatures, caused by global climate change or thermal
      effluent from industrial processes, may influence embryonic development of fish.
      This study investigates the cumulative effects of increased incubation
      temperature and repeated heat shocks on developing Lake Whitefish (Coregonus
      clupeaformis) embryos. We studied the effects of three constant incubation
      temperatures (2 degrees C, 5 degrees C or 8 degrees C water) and weekly, 1-h heat
      shocks (+3 degrees C) on hatching time, survival and morphology of embryos, as
      these endpoints may be particularly susceptible to temperature changes. The
      constant temperatures represent the predicted magnitude of elevated water
      temperatures from climate change and industrial thermal plumes. Time to the pre
      hatch stage decreased as constant incubation temperature increased (148d at 2
      degrees C, 92d at 5 degrees C, 50d at 8 degrees C), but weekly heat shocks did
      not affect time to hatch. Mean survival rates and embryo morphometrics were
      compared at specific developmental time-points (blastopore, eyed, fin flutter and
      pre-hatch) across all treatments. Constant incubation temperatures or +3 degrees
      C heat-shock exposures did not significantly alter cumulative survival percentage
      (~50% cumulative survival to pre-hatch stage). Constant warm incubation
      temperatures did result in differences in morphology in pre-hatch stage embryos.
      8 degrees C and 5 degrees C embryos were significantly smaller and had larger
      yolks than 2 degrees C embryos, but heat-shocked embryos did not differ from
      their respective constant temperature treatment groups. Elevated incubation
      temperatures may adversely alter Lake Whitefish embryo size at hatch, but weekly
      1-h heat shocks did not affect size or survival at hatch. These results suggest
      that intermittent bouts of warm water effluent (e.g., variable industrial
      emissions) are less likely to negatively affect Lake Whitefish embryonic
      development than warmer constant incubation temperatures that may occur due to
      climate change. 

PMID- 27033036
TI  - Fish pre-acclimation temperature only modestly affects cadmium toxicity in
      Atlantic salmon hepatocytes.
AB  - An emerging focus in environmental toxicology is how climate change will alter
      bioavailability and uptake of contaminants in organisms. Ectothermic animals
      unable to adjust their temperature by local migration, such as farmed fish kept
      in net pens, may become more vulnerable to contaminants in warmer seas. The aim
      of this work was to study cadmium (Cd) toxicity in cells obtained from fish
      acclimated to sub-optimal growth temperature. Atlantic salmon hepatocytes,
      harvested from fish pre-acclimated either at 15 degrees C (optimal growth
      temperature) or 20 degrees C (heat-stressed), were exposed in vitro to two
      concentrations of Cd (control, 1 and 100uM Cd) for 48h. Cd-induced cytotoxicity,
      determined with the xCELLigence system, was more pronounced in cells from fish
      pre-acclimated to a high temperature than in cells from fish grown at optimal
      temperature. A feed spiked with antioxidants could not ameliorate the Cd-induced
      cytotoxicity in cells from temperature-stressed fish. At the transcriptional
      level, Cd exposure affected 11 out of 20 examined genes, of which most are linked
      to oxidative stress. The transcriptional levels of a majority of the altered
      genes were changed in cells harvested from fish grown at sub-optimal temperature.
      Interaction effects between Cd exposure and fish pre-acclimation temperature were
      seen for four transcripts, hmox1, mapk1, fth1 and mmp13. Overall, this study
      shows that cells from temperature-stressed fish are modestly more vulnerable to
      Cd stress, and indicate that mechanisms linked to oxidative stress may be
      differentially affected in temperature-stressed cells. 

PMID- 27033037
TI  - Leptin regulates energy intake but fails to facilitate hibernation in fattening
      Daurian ground squirrels (Spermophilus dauricus).
AB  - Body fat storage before hibernation affects the timing of immergence in Daurian
      ground squirrels (Spermophilus dauricus). Leptin is an adipose signal and plays
      vital role in energy homeostasis mainly by action in brain. To test the
      hypothesis that leptin plays a role in facilitating the process of hibernation,
      squirrels were administrated with recombinant murine leptin (1MUg/day) through
      intracerebroventricular (ICV) injection for 12 days during fattening. From day 7
      to 12, animals were moved into a cold room (5+/-1 degrees C) with constant
      darkness which functioned as hibernaculum. Energy intake, body mass and core body
      temperature (Tb) were continuously monitored throughout the course of experiment.
      Resting metabolic rate (RMR) was measured under both warm and cold conditions. At
      the end of leptin administration, we measured the serum concentration of hormones
      related to energy regulation, mRNA expression of hypothalamic neuropeptides and
      uncoupling protein 1 (UCP1) levels in brown adipose tissue (BAT). Our results
      showed that during leptin administration, the cumulative food intake and increase
      of body mass were suppressed while Tb and RMR were unaltered. The proportion of
      torpid squirrels was not different between two groups. At the end of leptin
      administration, the expressions of hypothalamic neuropeptide Y and agouti gene
      related protein were suppressed. There were no differences in UCP1 mRNA
      expression or protein content in BAT between groups. Our data suggest that leptin
      can affect energy intake via hypothalamic neuropeptides, but is not involved in
      the initiation of hibernation in fattening Daurian ground squirrels. 

PMID- 27033038
TI  - Temperature-induced changes in fatty acid dynamics of the intertidal grazer
      Platychelipus littoralis (Crustacea, Copepoda, Harpacticoida): Insights from a
      short-term feeding experiment.
AB  - Dietary lipids, and in particular the essential fatty acids (EFA), EPA
      (20:5omega3) and DHA (22:6omega3), guarantee the well-being of animals and are
      recognized for their potential bottom-up control on animal populations. They are
      introduced in marine ecosystems through primary producers and when grazed upon,
      they are consumed, incorporated or modified by first-level consumers. As the
      availability of EFA in the ecosystem is affected by ambient temperature, the
      predicted rise in ocean temperature might alter the availability of these EFA at
      the basis of marine food webs. Despite the FA bioconversion capacity of certain
      benthic copepod species, their lipid (FA) response to varying temperatures is
      understudied. Therefore, the temperate, intertidal copepod Platychelipus
      littoralis was offered a mono and mixed diatom diet at 4, 15  degrees C (normal
      range) and at 24  degrees C (elevated temperature) to investigate the combined
      effects of temperature and resource availability on its FA content and
      composition. P. littoralis showed a flexible thermal acclimation response. Cold
      exposure increased the degree of FA unsaturation and the EPA%, and induced a
      shift towards shorter chain FA in the copepod's membranes. Furthermore, a mixed
      diet reduced the impact of heat stress on the copepod's membrane FA composition.
      Temperature affected the trophic transfer of EPA and DHA differently. While
      dietary resources could fully compensate for the temperature effects on total
      lipid and EPA content in the copepods, no such counterweigh was observed for the
      DHA dynamics. Heat stress lowered the DHA concentration in copepods regardless of
      the resources available and this implies negative effects for higher trophic
      levels. 

PMID- 27033039
TI  - Novel approaches to the calculation and comparison of thermoregulatory
      parameters: Non-linear regression of metabolic rate and evaporative water loss in
      Australian rodents.
AB  - The calculation and comparison of physiological characteristics of
      thermoregulation has provided insight into patterns of ecology and evolution for
      over half a century. Thermoregulation has typically been explored using linear
      techniques; I explore the application of non-linear scaling to more accurately
      calculate and compare characteristics and thresholds of thermoregulation,
      including the basal metabolic rate (BMR), peak metabolic rate (PMR) and the lower
      (Tlc) and upper (Tuc) critical limits to the thermo-neutral zone (TNZ) for
      Australian rodents. An exponentially-modified logistic function accurately
      characterised the response of metabolic rate to ambient temperature, while
      evaporative water loss was accurately characterised by a Michaelis-Menten
      function. When these functions were used to resolve unique parameters for the
      nine species studied here, the estimates of BMR and TNZ were consistent with the
      previously published estimates. The approach resolved differences in rates of
      metabolism and water loss between subfamilies of Australian rodents that haven't
      been quantified before. I suggest that non-linear scaling is not only more
      effective than the established segmented linear techniques, but also is more
      objective. This approach may allow broader and more flexible comparison of
      characteristics of thermoregulation, but it needs testing with a broader array of
      taxa than those used here. 

PMID- 27033040
TI  - Urban roost temperatures of large-spotted-genets: The effect of anthropogenic
      structures.
AB  - Generally, large-spotted genets (Genetta tigrina) use tree hollows and canopies
      as daytime roosts during their inactive phase. However, there has been an
      increasing tendency for individuals to make use of anthropogenic structures, such
      as roofs, within urban landscapes in KwaZulu-Natal, South Africa. This study
      investigated the roosting thermal dynamics of large-spotted genets within the
      urban suburbs of Kloof. Roost temperatures were recorded with i-Button(r)
      temperature loggers at known large-spotted genet roosts in anthropogenic
      structures as well as in natural roost sites. Over the seasons, temperatures
      varied significantly between months and among different roosts. However,
      anthropogenic roost temperatures were higher than ambient temperatures throughout
      the study period. Furthermore, anthropogenic roosts had higher temperatures (with
      lower variability) than natural roost sites. This study highlighted the
      importance of anthropogenic structures as daytime roosts for large-spotted genets
      within an urban mosaic. However, high temperatures experienced during the summer
      can be detrimental to juvenile large-spotted genets resulting in plasticity of
      breeding behaviour and a switch to producing young in cooler months. 

PMID- 27033041
TI  - Do female newts modify thermoregulatory behavior to manipulate egg size?
AB  - Reproductive females manipulate offspring phenotypes by modifying conditions
      during embryogenesis. In ectotherms, the environmental control over embryogenesis
      is often realized by changes in maternal thermoregulation during gravidity. To
      determine if reproduction influences thermoregulatory behavior in species where
      females lay eggs shortly after fertilization (strict oviparity), we compared
      preferred body temperatures (Tp) between reproductive (egg-laying) and non
      reproductive female newts, Ichthyosaura alpestris. Next, we exposed reproductive
      females to temperatures mimicking Tp ranges of reproductive and non-reproductive
      individuals to find out whether the maternally modified thermal regime influences
      ovum and jelly coat volume, and early cleavage rates at the time of oviposition.
      In the thermal gradient, reproductive females maintained their body temperatures
      within a narrower range than non-reproductive individuals. The exposure of
      ovipositing females to temperatures preferred during their reproductive and non
      reproductive period had a negligible influence on egg size and early cleavage
      rates. We conclude that the modification of maternal thermoregulatory behavior
      provides a limited opportunity to manipulate egg traits in newts. 

PMID- 27033042
TI  - An instantaneous approach for determining the infrared emissivity of swine
      surface and the influencing factors.
AB  - Infrared thermal imaging technology has been widely employed in temperature
      measurements of human and animals and its accuracy relies on the determination
      process of the emissivity of the target to a large extent. However, common used
      methods were unable to determine the emissivity of the surface of living animals
      and thus lower the accuracy. In this paper, we suggested a new approach to
      acquire the infrared emissivity of living swine in real time. In the approach,
      the surface temperature of swine and reference body were measured to compute the
      emissivity and the measurement process was completed in a non-contact and non
      invasive manner. We changed the surface reflection energy of animals and
      reference body by changing the ambient radiant energy and obtain the surface
      emissivity in real time without confirming the actual temperature of animal
      surface. In this way, the infrared emissivity of the animal surface can be
      determined instantaneously and without knowing the real temperature. Both swine
      specimen and a living swine were used in this study. Using this method, we
      measured the emissivity of different body sites of the swine. The results showed
      that the emissivity values at different body sites show the significant
      differences. The emissivity values at trotter and eye were respectively 0.895 and
      0.930 and the emissivity on swine surface varied from 0.945 to 0.978. More
      important, the distribution of the infrared emissivity on a living swine was
      explored and the detailed differences of the emissivity on a swine surface can be
      cleanly seen. Furthermore, we studied the influencing factors on the emissivity
      of animal surface, through measuring the emissivity distribution on swine surface
      when pig specimens were sprayed with water on the surface or heated using this
      method. This study is of great significance for the accurate measurement of swine
      surface temperature. 

PMID- 27033043
TI  - Prenatal heat stress reduces male anogenital distance at birth and adult testis
      size, which are rescued by concurrent maternal Artemisia absinthium consumption.
AB  - Boars from sows with elevated plasma cortisol during pregnancy have shorter
      anogenital distance (AGD), a trait associated with subfertility. Since gestating
      sows often experience summer heat stress (HS), a mouse model was used to evaluate
      the effect of prenatal HS on AGD and fertility; efficacy of the heat stress
      mitigating supplement Artemisia absinthium (AB) was also evaluated. Dams were
      treated from d 8-18 of gestation, residing in ambient temperatures from 0700 to
      1900h. From 1900 to 0700h females were exposed to 34.13+/-0.27 degrees C (HS)
      with access to water (HSW; n=9), HS with access to a 1% w/v decoction of AB (HSA;
      n=9), 20.81+/-0.20 degrees C (thermal neutral; TN) with water (TNW; n=10) or TN
      with AB (TNA; n=10). Daily liquid consumption was measured from d 6-18, and tail
      temperature was recorded at 0700 and 1900h from d 8-18. Progeny weight and AGD
      were recorded at birth and weaning. At maturity, males were mated to non
      littermate females from each treatment; these females were euthanized after 16 d
      of TN gestation. Reproductive traits were compared among all male/female
      treatment combinations; testes were weighed. Average liquid intake differed among
      treatments with HS and AB animals drinking more (P<0.0004). A treatment by time
      interaction for tail temperature (P<0.001) was observed; HS increased tail
      temperature of HSA and HSW animals similarly compared to TNA and TNW. Treatment
      affected (P<0.01) male birth AGD (HSW shortest; P<0.07). At maturity, HSW males
      also had the smallest testes (P<0.02). However, we observed no differences in
      fertility (P>0.10). These data indicate that in utero HS decreases both male
      birth AGD and adult testis size, effects which maternal AB consumption mitigates.

PMID- 27033044
TI  - Exposure to solar radiation drives organismal vulnerability to climate: Evidence
      from an intertidal limpet.
AB  - Understanding the physiological abilities of organisms to cope with heat stress
      is critical for predictions of species' distributions in response to climate
      change. We investigated physiological responses (respiration and heart beat rate)
      of the ectotherm limpet Patella vulgata to heat stress events during emersion and
      the role of seasonal and microclimatic acclimatization for individual thermal
      tolerance limits. Individuals were collected from 5 microhabitats characterized
      by different exposure to solar radiation in the high intertidal zone of a semi
      exposed rocky shore in winter and summer of 2014. Upper thermal tolerance limits
      (heat coma temperatures - HCTs, and heart rate Arrhenius break temperatures -
      ABTs) were determined for individuals from each microhabitat in both seasons
      under laboratory conditions. While we found a clear seasonal acclimatization,
      i.e., higher HCTs and ABTs in summer than in winter, we did not find evidence for
      microhabitat-specific responses that would suggest microclimatic acclimatization.
      However, operative limpet temperatures derived from in-situ temperature
      measurements suggest that individuals from sun exposed microhabitats have a much
      narrower thermal safety margins than those from less exposed surfaces or within
      crevices. Microhabitat specific thermal safety margins caused by high thermal
      heterogeneity at small spatial scales and the lack of short term acclimatization
      will likely shape small scale distribution patterns of intertidal species in
      response to the predicted increase in the frequency and intensity of heat waves. 

PMID- 27033045
TI  - Thermal biology of Pacific cicada killers, Sphecius convallis Patton, in the
      Upper Sonoran Desert.
AB  - A comprehensive investigation of the Pacific cicada killer, Sphecius convallis
      Patton, was undertaken to examine the behavioral and physiological mechanisms by
      which they are able to complete their life cycle in the thermal extremes of the
      Upper Sonoran Desert. S. convallis were endothermic, exhibiting elevated and
      relatively constant thorax temperatures during many activities. Males basked in
      trees at dawn to warm up, then used a variety of behaviors and perching
      strategies to maintain thorax temperature during territorial behavior. The thorax
      temperature of females was highest during provisioning and orientation flights,
      somewhat lower while investigating burrows, and lowest while digging burrows. The
      optimal thorax temperature for flight was about 40 degrees C, which was
      approximated most closely by males resting in the shade during the afternoon. In
      mating clusters, the mated male was the hottest, the female was coolest and the
      other males were intermediate. Wasps lost about 5% of body mass during heating
      treatments, and may use evaporative water loss for cooling. Pacific cicada
      killers use a complex suite of behavioral and physiological adaptations to
      regulate body temperature during their nesting season. 

PMID- 27033046
TI  - Identification, genomic organization and expression profiles of four heat shock
      protein genes in the western flower thrips, Frankliniella occidentalis.
AB  - The western flower thrips, Frankliniella occidentalis, is an important invasive
      pest with a strong tolerance for extreme temperatures; however, the molecular
      mechanisms that regulate thermotolerance in this insect remain unclear. In this
      study, four heat shock protein genes were cloned from F. occidentalis and named
      Fohsp90, Fohsc701, Fohsc702 and Fohsp60. These four Hsps exhibited typical
      characteristics of heat shock proteins. Subcellular localization signals and
      phylogenetic analysis indicated that FoHsp90 and FoHsc701 localize to the
      cytosol, whereas FoHsc702 and FoHsp60 were located in the endoplasmic reticulum
      and mitochondria, respectively. Analysis of genomic sequences revealed the
      presence of introns in the four genes (three, four, seven, and five introns for
      Fohsp90, Fohsc701, Fohsc702 and Fohsp60, respectively). Both the number and
      position of introns in these four genes were quite different from analogous genes
      in other species. qRT-PCR indicated that the four Fohsps were detected in second
      stage larvae, one-day-old pupae, and one-day-old adults, and mRNA expression
      levels were lowest in larvae and highest in pupae. Fohsc701 and Fohsc702
      possessed similar expression patterns and were not induced by cold or heat
      stress. Expression of Fohsp60 was significantly elevated by heat, and Fohsp90 was
      rapidly up-regulated after exposure to both cold and heat stress. Exposure to -8
      degrees C had no effect on expression of the four Fohsps; however, expression of
      Fohsp90 and Fohsp60 was highest after a 2-h incubation at 39 degrees C.
      Furthermore, cold and heat hardening led to significant up-regulation of the four
      Fohsps compared to their respective controls. Collectively, our results indicate
      that the four FoHsps contribute to insect development and also function in rapid
      cold or heat hardening; furthermore, FoHsp90 and FoHsp60 contribute to
      thermotolerance in F. occidentalis. 

PMID- 27033047
TI  - Trends of acute kidney injury after radical or partial nephrectomy for renal cell
      carcinoma.
AB  - OBJECTIVES: To investigate the prevalence, temporal trends, and predictors of
      postoperative acute kidney injury (AKI) in a large cohort of patients with renal
      cell carcinoma treated with radical or partial nephrectomy. METHODS: Between
      January 1998 and December 2010, patients who underwent radical or partial tumor
      nephrectomy were identified within the Nationwide Inpatient Sample. First,
      prevalence and temporal trends of AKI were analyzed. Second, predictors of AKI
      were identified using multivariable regression analyses. Third, associations
      between AKI and in-hospital complications, length of stay, hospital costs, and in
      hospital mortality were evaluated using logistic regression models adjusted for
      clustering. RESULTS: Of total 253,046 patients, 5.5% (14,303 in radical and 3,525
      in partial nephrectomy) experienced AKI. Rates of AKI significantly increased
      from 2.0% in 1998 to 10.4% in 2010 (P<0.001). Predictors of AKI included male
      sex, radical nephrectomy, more contemporary years (2004-2010), older age, black
      race, higher comorbidities, higher preoperative chronic kidney disease stage,
      Medicare insurance status, and nephrectomy at urban hospitals (all P<0.01).
      Postoperative AKI during hospitalization was associated with an increased rate of
      in-hospital mortality, any complications, transfusion, prolonged length of stay,
      and higher hospital costs (all P<0.001). CONCLUSIONS: Rising rates of in-hospital
      AKI after radical and partial nephrectomy were observed. Increasing awareness of
      AKI, identification of patients at risk before surgery, early postoperative AKI
      diagnosis, collaboration with nephrologists, implementation of renoprotective
      strategies, long-term renal functional follow-up, and a well-designed prospective
      study, may be warranted.

PMID- 27033048
TI  - Diagnostic performance of procalcitonin for bacteremia in patients with severe
      dengue infection in the intensive care unit.

PMID- 27033049
TI  - Esophageal dilatation and interstitial lung disease in systemic sclerosis: A
      cross-sectional study.
AB  - OBJECTIVE: A patulous esophagus on high-resolution computed tomography (HRCT) of
      the thorax is frequently observed in patients with systemic sclerosis (SSc).
      Microaspiration has been purported to play a role in the development and
      progression of SSc interstitial lung disease (ILD), but studies examining the
      role of microaspiration in SSc ILD have yielded conflicting results. This study
      was conducted to determine the association between esophageal diameter and SSc
      ILD. METHODS: A cross-sectional study of Northwestern Scleroderma Registry
      patients with available HRCT exams was conducted. The predictor variable was the
      widest esophageal diameter (WED) on HRCT, and the primary and secondary outcome
      variables were radiographic ILD and pulmonary function tests respectively. The
      degree of radiographic ILD was assessed using a semi-quantitative score adapted
      from published methods. Estimated regression coefficients adjusted for age, sex,
      race, body mass index, smoking; SSc disease subtype, serum autoantibodies, and
      disease duration; modified Rodnan skin score, proton pump inhibitor, and immune
      suppressant medication use and erythrocyte sedimentation rate were calculated.
      RESULTS: A total of 270 subjects were studied. In the adjusted analyses, there
      were positive associations between WED and total ILD score (beta = 0.27; 95% CI:
      0.09-0.41), fibrosis (beta = 0.15; 95% CI: 0.07-0.23), and ground glass opacities
      (beta = 0.12; 95% CI: 0.04-0.20); there were negative associations between WED
      and FVC % predicted (beta = -0.42; 95% CI: -0.69 to -0.13), and adjusted DLCO %
      predicted (beta = -0.45; 95% CI: -0.80 to -0.09) after adjusting for potential
      confounders. CONCLUSIONS: Increasing esophageal diameter on HRCT in patients with
      SSc is associated with more severe radiographic ILD, lower lung volumes, and
      lower DLCO % predicted. Longitudinal studies are needed to determine if
      esophageal dilatation is associated with the incidence and/or progression of ILD
      in patients with SSc.

PMID- 27033050
TI  - Expression of miRNA-26b in the diagnosis and prognosis of patients with non-small
      cell lung cancer.
AB  - OBJECTIVE: To investigate the correlation between miR-26b and non-small-cell lung
      cancer (NSCLC). MATERIALS & METHODS: NSCLC tissues and normal lung tissues that
      were more than 7 cm adjacent from tumor were collected from 154 NSCLC patients.
      Additionally, 63 normal specimens from benign lung disease were selected as the
      control group. Real-time fluorescent quantitative PCR was used to detect miR-26b
      expression in tissues. RESULT: miR-26b expression in NSCLC tissues was
      significantly lower than in other two types of tissues. Receiver operating
      characteristic curve analysis showed that the area under the curve was 0.856 with
      sensitivity and specificity of 79.9 and 79.4%, respectively. miR-26b expression
      was a risk factor for poor prognosis of NSCLC. CONCLUSION: The expression of miR
      26b is downregulated in NSCLC tissues, and it might be useful in the diagnosis
      and prognosis of NSCLC patients.

PMID- 27033051
TI  - Restructuring of the extracellular matrix in diabetic wounds and healing: A
      perspective.
AB  - Diabetic foot ulcers are a complication of diabetes for which treatment options
      are limited and not effective, resulting in 73,000 lower-limb amputations in the
      United States every year. Wound healing is a complex process with a highly
      orchestrated cascade of events, in which the extracellular matrix (ECM) interacts
      with growth factors and cells. Matrix metalloproteinases (MMPs) are involved in
      all wound healing events, in particular MMP-8 and MMP-9, whose physiological
      functions are to degrade damaged collagen type I and to facilitate keratinocyte
      migration and re-epithelialization, respectively. MMP substrate redundancy
      permits another MMP to substitute for MMP-9 during normal wound healing. Under
      the hypoxic and inflammatory environment of diabetic wounds, increased reactive
      oxygen species (ROS) and upregulation of MMP-9 results in wounds that are
      recalcitrant to healing. We have determined that MMP-8 plays a role in the body's
      response to wound healing and that MMP-9 is the pathological consequence of the
      disease with detrimental effects. Thus, selective inhibition of MMP-9, while
      leaving MMP-8 activity unaffected, is desirable. ND-336 has such inhibitory
      profile and is a promising strategy for treatment of diabetic foot ulcers.

PMID- 27033052
TI  - Association of Apolipoprotein E (ApoE) Polymorphism with Alzheimer's Disease in
      Chinese Population.
AB  - Apolipoprotein E (ApoE) plays a vital role in cholesterol metabolism and its
      allele polymorphisms have been associated with several diseases including
      Alzheimer's disease (AD). There are few systematic studies on ApoE polymorphism
      and its association with AD in Chinese population. To examine this issue,
      participants included 4251 subjects and 404 AD patients with 390 healthy elderly
      residing in Chongqing city were genotyped. The results showed that the epsilon3
      allele presented the highest frequency (82%), followed by epsilon4 (6.25%) and
      epsilon2 (11.75%) in general population. epsilon3/epsilon3 genotype carriers are
      the most common ones (64.19%) and the epsilon4/epsilon4 had the lowest frequency
      (0.59%). The frequency of ApoEepsilon4 allele frequency in AD (15.35%) was
      significantly higher than control (10.00%). Those carriers of two epsilon4 allele
      have five time higher risk to develop AD. Our study demonstrate that ApoEepsilon4
      allele is a risk factor of AD for Chinese population.

PMID- 27033054
TI  - DNA Double Strand Breaks: A Common Theme in Neurodegenerative Diseases.
AB  - Accumulation of DNA damage and impairment of DNA repair systems are involved in
      the pathogenesis of different neurodegenerative diseases. Whenever DNA damage is
      too extensive, the DNA damage response pathway provides for triggering cellular
      senescence and/or apoptosis. However, whether the increased level of DNA damage
      in neurodegenerative disorders is a cause rather than the consequence of
      neurodegenerative events remains to be established. Among possible DNA lesions,
      DNA double strand breaks (DSBs) are rare events, nevertheless they are the most
      lethal form of DNA damage. In neurons, DSBs are particularly deleterious because
      of their reduced DNA repair capability as compared to proliferating cells. Here,
      we provide a description of DSB repair systems and describe human studies showing
      the presence of several types of DNA lesions in three major neurodegenerative
      diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and
      Huntington's disease (HD). Then, we analyze the role of DSB accumulation and
      deficiency of DSB repair systems in neurodegeneration by examining studies on
      animal models of neurodegenerative diseases.

PMID- 27033053
TI  - Alzheimer's Disease Genetic Risk Factor APOE-epsilon4 Also Affects Normal Brain
      Function.
AB  - APOE-epsilon4 is the strongest genetic risk factor for Alzheimer's disease (AD),
      and is associated with an increase in the levels of amyloid deposition and an
      early age of onset. Recent data demonstrate that AD pathological changes occur
      decades before clinical symptoms, raising questions about the precise onset of
      the disease. Now a convergence of approaches in mice and humans has demonstrated
      that APOE-epsilon4 affects normal brain function even very early in life in the
      absence of gross AD pathological changes. Normal mice expressing APOE4 have task
      specific spatial learning deficits, as well as reduced NMDAR-dependent signaling
      and structural changes to presynaptic and postsynaptic compartments in neurons,
      particularly in hippocampal regions. Young humans possessing APOE-epsilon4 are
      more adept than APOE-epsilon4 negative individuals at some behavioral tasks, and
      functional magnetic resonance imaging has shown that inheritance of APOE-epsilon4
      has specific effects on medial temporal brain activities. These findings suggest
      that inheritance of APOE-epsilon4 causes life long changes to the brain that may
      be related to the late risk of AD. Several possible mechanisms of how APOE
      epsilon4 could affect brain neurochemistry, structure, and function are reviewed.

PMID- 27033055
TI  - Glucagon-Like Peptide-1-Mediated Modulation of Inflammatory Pathways in the
      Diabetic Brain: Relevance to Alzheimer's Disease.
AB  - Neuroinflammation has emerged as an important cause of cognitive decline during
      aging and in Alzheimer's disease (AD). Chronic low-grade inflammation is observed
      in obesity and diabetes, which are important risk factors for AD. Therefore, we
      examined the markers of inflammation in the brain hippocampal samples of Zucker
      diabetic fatty (ZDF) rats. Pathway-specific gene expression profiling revealed
      significant increases in the expression of oxidative stress and inflammatory
      genes. Western blot analysis further showed the activation of NF-kB, defective
      CREB phosphorylation, and decreases in the levels of neuroprotective CREB target
      proteins, including Bcl-2, BDNF, and BIRC3 in the diabetic rat brain samples, all
      of which are related to AD pathology. As therapies based on glucagon-like peptide
      1 (GLP-1) are effective in controlling blood glucose levels in type 2 diabetic
      patients, we tested the in vivo actions of GLP-1 in the diabetic brain by a 10-wk
      treatment of ZDF rats with alogliptin, an inhibitor of dipeptidyl peptidase.
      Alogliptin increased the circulating levels of GLP-1 by 125% and decreased blood
      glucose in diabetic rats by 59%. Normalization of defective signaling to CREB in
      the hippocampal samples of treated diabetic rats resulted in the increased
      expression of CREB targets. Dual actions of GLP-1 in the pancreatic beta cells
      and in the brain suggest that incretin therapies may reduce cognitive decline in
      the aging diabetic patients and also have the potential to be used in treating
      Alzheimer's patients.

PMID- 27033056
TI  - Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling
      Imbalance in Aluminum-Overload Rats.
AB  - Although COX-2 inhibition in animal models of neurodegenerative diseases has
      shown neuroprotection, recent studies have revealed some serious side effects
      (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits
      of COX-2 inhibitors. A more focused approach is necessary to explore the
      therapeutic effect of the COX downstream signaling pathway in neurological
      research. The aim of this study was to explore the alterations of the PGES-PGE2
      EP signal pathway and the effect of misoprostol on neurodegeneration by chronic
      aluminum-overload in rats. Adult rats were treated by intragastric administration
      of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the
      hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis,
      respectively. The content of malondialdehyde (MDA) and the activity of superoxide
      dismutase (SOD) in the rat hippocampi were also detected. The misoprostol
      treatment dose-dependently improved spatial learning and memory function as well
      as healing after hippocampal neuron damage induced by chronic aluminum-overload
      in rats. Meanwhile, the administration of misoprostol resulted in a decrease in
      the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels,
      while there was a dosedependent up-regulation of EP3 expression. These results
      suggest that misoprostol possesses a neuroprotective property, and the mechanism
      involves affecting the EP3 level and reducing the endogenous production of PGE2
      through a negative feedback mechanism, increasing the EP3 expression level,
      decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1
      4 signal pathway balance. In this way, misoprostol has a counteractive effect on
      oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs
      signaling pathway is a potential therapeutic strategy for treating
      neurodegeneration in patients.

PMID- 27033057
TI  - Inflammation, Oxidation, Caloric Expenditure and Cognitive Impairment in
      Brazilian Elderly Assisted at Primary Care.
AB  - Cognitive impairment (CI) has a multifactorial etiology. Some studies have
      suggested that inflammatory, oxidative and antioxidant status and physical
      activity are associated with CI. However, the evidence on this subject is still
      controversial. The goal of this study was to verify the association of caloric
      expenditure by physical activity, oxidative, antioxidant power and inflammatory
      biomarkers with CI in older adults. We performed a cross-sectional study of 424
      elderly (224 with normal cognitive function and 200 with CI) patients from the
      Family Health Strategy in Porto Alegre, Rio Grande do Sul, Brazil. The variables
      investigated were sociodemographic, biochemical, inflammatory (hs-CRP, IL-6),
      oxidative (TBARS, AOPP), antioxidant power (FRAP) biomarkers, energy expenditure,
      and cognitive function. The instruments used were the Minnesota Leisure Time
      Physical Activity Questionnaire + Compendium of Physical Activities,
      classification of energy costs of human physical activities (for physical
      activity evaluation and measurement of energy expenditure in METs), and a battery
      of neuropsychiatric instruments (for cognitive ability assessment). We found
      statistically significant differences only with respect to HDL-c and age (higher
      averages in the CI group; P<0.05). We observed no differences between the groups
      with respect to biochemical, inflammatory, oxidative and FRAP biomarkers or
      caloric expenditure. Logistic regression showed that HDL-c (OR=1.02 [IC=95%; 1.01
      1.04]; P=0.011), and age (OR=1.05 [IC=95%; 1.02-1.08]; P=0.004) are independent
      factors associated with CI. Our results suggest that the biochemical (except HDL
      c), inflammatory, oxidative, and FRAP biomarkers investigated and caloric
      expenditure are not associated with CI in the elderly assisted at primary care.

PMID- 27033058
TI  - Substance P and Alzheimer's Disease: Emerging Novel Roles.
AB  - Alzheimer's disease (AD) is an irreversible neurodegenerative disease, clinically
      characterized by progressive impairments of memory and cognition. The hallmarks
      of AD are neurofibrillary tangles, mainly constituted by altered phosphorylated
      and truncated portions of tau protein, and the abnormal extracellular deposition
      of neurotoxic beta amyloid (Abeta) peptides, derived from the proteolytic
      processing of amyloid precursor protein (APP). According to the amyloid
      hypothesis, Abeta is considered to be linked to the selective neurodegeneration
      seen in AD. Recent evidence points to an increase in voltage-gated potassium (Kv)
      channel currents in the etiology of Abeta-induced neuronal apoptosis. Substance P
      (SP) is an 11-aa neuropeptide, member of the tachykinin family, broadly
      distributed in the Central Nervous System where it acts as a neurotransmitter,
      neuromodulator, and neurotrophic factor. This peptide may play an important role
      in neurodegenerative disorders, since reduced levels of SP were found in brain
      areas and spinal fluid of AD patients. In addition to its neuroprotective
      properties, it was recently demonstrated that SP is able to stimulate non
      amyloidogenic APP processing, thereby reducing the possibility of generation of
      toxic Abeta peptides in the brain. Recent studies, using in vitro and in vivo
      models, have also shown that the neuroprotective role of SP against Abeta could
      be related to its ability of modulate Kv channel currents. In this review, we
      briefly summarized the current findings on the neurotrophic and neuroprotective
      effects of SP, providing information about its anti-amyloidogenic and anti-Abeta
      toxicity role.

PMID- 27033059
TI  - Radiation-induced CT number changes in GTV and parotid glands during the course
      of radiation therapy for nasopharyngeal cancer.
AB  - OBJECTIVE: To investigate the changes in CT number (CTN) in gross tumour volume
      (GTV) and organs at risk (OARs) during the course of radiation therapy (RT) for
      nasopharyngeal cancer (NPC). METHODS: Daily megavoltage CT (MVCT) data collected
      from 30 patients with NPC treated with a prescription dose of 70 Gy in 30-33
      fractions using helical tomotherapy were retrospectively analyzed. The contours
      of GTV and OARs on daily MVCTs were obtained by populating the planning contours
      from planning CT to daily MVCTs with manual editing, if necessary. The changes of
      GTV and OAR volumes and the histograms of CTN in the GTV and OARs during the
      course of RT delivery were analyzed. RESULTS: Volumes of GTV and parotid glands
      were reduced during the course of radiation treatment, with an average shrinkage
      rate of 0.23% per day (range, 0.02-0.8%) and 1.2% per day (range, 0.2-2.3%),
      respectively. The mean CTN changes in GTV and ipsilateral and contralateral
      parotid glands were reduced by 52 +/- 35 HU, 18 +/- 20 HU and 17 +/- 22 HU,
      respectively. For GTV, the CTN and GTV volume decreases were found to be
      correlated with each other (p < 0.0001). No noticeable CTN change was found in
      the spinal cord and non-specified tissue irradiated with low doses. CONCLUSION:
      The CTN changes in GTV and parotids are measurable during the delivery of
      fractionated radiotherapy for NPC, were associated with the doses received (the
      number of fractions delivered) and were patient specific. ADVANCES IN KNOWLEDGE:
      The CTN change during radiotherapy is dose dependent and is measurable for NPC.

PMID- 27033060
TI  - Executive dysfunction is associated with poorer health-related quality of life in
      pediatric brain tumor survivors.
AB  - Children with a brain tumor (BT) are at risk for a number of physical and
      cognitive problems that may lower their health-related quality of life (HRQoL).
      Executive functioning (EF) and intellectual ability are hypothesized to associate
      with HRQoL and deficits in these areas may be amenable to interventions. This
      study aimed to investigate intellectual function, EF, and HRQoL following
      conformal radiation therapy (CRT) for pediatric BT. Forty-five BT survivors (age
      12.68 +/- 2.56) treated with CRT participated. Thirty-six siblings of BT patients
      (age 12.36 +/- 2.13) and 33 survivors of non-CNS solid tumors (ST; age 12.18 +/-
      2.88) were comparison groups. IQ estimate (Wechsler Abbreviated Scale of
      Intelligence; WASI), EF ratings (Behavior Rating Inventory of Executive Function;
      BRIEF), and HRQoL ratings (KINDL-R) were obtained. BT survivors reported lower
      overall HRQoL than ST survivors (p = .012). Parents reported lower overall HRQoL
      for BT survivors than siblings (p = .014). Parent-report on individual areas of
      HRQoL was higher than self-report for most subscales. IQ and HRQoL ratings were
      not related (Parent r = .17, p = .27; Child r = .11, p = .49). EF ratings
      correlated with Parent (r = -.15 to -.73) but not Child HRQoL ratings. Children
      with BT experienced poorer HRQoL than controls. Children's HRQoL was consistently
      rated higher by parent- than self-report across all domains. HRQoL was associated
      with EF, but not with IQ. These findings identify interventions targeting EF
      (e.g., cognitive rehabilitation, medication) as a possible avenue for improving
      HRQoL in childhood BT survivors.

PMID- 27033061
TI  - Diffuse astrocytoma arising within a demyelinating plaque.

PMID- 27033062
TI  - Reduction in Hepatocyte Growth Factor Serum Levels is Associated with Improved
      Prognosis in Advanced Lung Adenocarcinoma Patients Treated with Afatinib: a Phase
      II Trial.
AB  - BACKGROUND: C-met and its ligand, hepatocyte growth factor (HGF) have been
      associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a
      clinical-marker of response in NSCLC patients treated with afatinib. METHODS:
      Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any
      line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status
      were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF
      content was measured by ELISA before and 2 months after the start of treatment.
      HGF levels were assessed with the objective response rate (ORR), progression-free
      survival (PFS), and overall survival (OS). This trial was registered on
      ClinicalTrials.gov: NCT01542437. RESULTS: Fifty patients (75 %) were EGFR
      mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR
      mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9
      18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5
      28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients,
      respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44
      %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS
      (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was
      an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR
      0.31; p = 0.006) in all and EGFR mutated patients. CONCLUSIONS: A reduction in
      serum HGF levels was associated with improved outcomes in patients treated with
      afatinib. These results suggest HGF might have a role as a mechanism of
      resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to
      prevent or reverse resistance particularly in EGFR mutated patients.

PMID- 27033063
TI  - The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and
      Laboratory Parameters in Stage IV Colorectal Cancer.
AB  - Our aim was to evaluate the predictive and prognostic influence of BRAF mutation
      and other molecular, clinical and laboratory parameters in stage IV colorectal
      cancer (CRC). 60 patients were included in this retrospective analysis, and 17
      variables were examined for their relation with treatment response and survival.
      KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and
      10.5 % respectively. 29.8 % of patients responded to treatment. Median survival
      time was 14.3 months. Weight loss, fever, abdominal metastases, blood
      transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were
      associated with survival. In multivariate analysis, male patients had 3.8 times
      higher probability of response, increased DNA Index was inversely correlated with
      response and one unit raise of DNA Index augmented 6 times the probability of
      death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and
      ploidy in advanced CRC. 

PMID- 27033064
TI  - Users' participation in nursing care: an element of the Theory of Goal
      Attainment.
AB  - BACKGROUND: Users' participation in care has been acknowledged as a key factor to
      improve health services. AIM: To analyze the Theory of Goal Attainment and to
      discuss the explicit and implicit relations between the Theory and the phenomenon
      of users' participation in nursing care. DESIGN: Theoretical analysis of the
      Theory of Goal Attainment. METHODS: The analysis phase of the Framework for
      Analysis and Evaluation of Nursing Theories was applied. Then, the explicit and
      implicit relations between the Theory and the phenomenon of users' participation
      were analyzed. RESULTS: Users' participation in nursing care is an element of the
      Theory of Goal Attainment, although limited to the goal setting and the means to
      achieve them. CONCLUSION: The choice for users' participation in care is a right
      defended in health policies around the world. The Theory of Goal Attainment is an
      appropriate guide to nurses in defense of users' participation in nursing care.

PMID- 27033065
TI  - Amino acid profiling as a method of discovering biomarkers for early diagnosis of
      cancer.
AB  - Cancer is one of the main causes of mortality in the world and its early
      detection significantly increases chances of patients' survival. High cancer
      mortality rate is caused mainly by late-stage diagnosis and lack of non-invasive
      and reliable methods for early diagnosis, such as plasma biomarkers. The
      incidence of cancers in the world still grows so it is crucial to develop a new,
      faster, high specificity and more sensitive diagnostic technologies. Several
      recent researchers indicate amino acids as a potential marker for cancer
      detection. An ideal cancer biomarker should be characterized by high specificity
      and sensitivity, reliability, ease of measurement and, what is important, ability
      to detect disease in its early stage. This study is focused on indicating
      metabolic amino acid profiling as a method of identifying biomarkers for cancer
      early detection and screening. Presented results are derived from the most recent
      studies where patients in early, often asymptomatic stages of disease constituted
      a large percentage of all the patients and, what is important, where researchers
      have observed alterations in these patients' amino acid profiles. This review is
      concentrated on analyzing studies on the most common cancers with high mortality
      rate. Inventing effective methods of early diagnosis is particularly important in
      case of such diseases. Research presented in this publication is focused on
      patients with lung, breast and colon cancer. In all analyzed cases, significant
      changes in the amino acid profile in cancer patients comparing to healthy
      controls were observed. This study indicates potential of amino acid profiling as
      method for early cancer detection.

PMID- 27033066
TI  - PTEN: History of a Tumor Suppressor.
AB  - Starting from the discovery of "inhibitory chromosomes" by Theodor Boveri to the
      finding by Henry Harris that fusing a normal cell to a cancer cell reduced
      tumorigenic potential, the notion of tumor suppression was recognized well before
      any tumor-suppressor genes were discovered. Although not the first to be
      revealed, PTEN has been demonstrated to be one of the most frequently altered
      tumor suppressors in cancer. This introductory chapter provides a historical
      perspective on our current understanding of PTEN including some of the seminal
      discoveries in the tumor suppressor field, the events leading to PTEN's
      discovery, and an introduction to some of the most important researchers and
      their studies which have shed light on PTEN biology and function as we know it
      today. 

PMID- 27033067
TI  - PTEN at 18: Still Growing.
AB  - Discovered in 1997, PTEN remains one of the most studied tumor suppressors. In
      this issue of Methods in Molecular Biology, we assembled a series of papers
      describing various clinical and experimental approaches to studying PTEN
      function. Due to its broad expression, regulated subcellular localization, and
      intriguing phosphatase activity, methodologies aimed at PTEN study have often
      been developed in the context of mutations affecting various aspects of its
      regulation, found in patients burdened with PTEN loss-driven tumors. PTEN's
      extensive posttranslational modifications and dynamic localization pose unique
      challenges for studying PTEN features in isolation and necessitate considerable
      development of experimental systems to enable controlled characterization.
      Nevertheless, ongoing efforts towards the development of PTEN knockout and knock
      in animals and cell lines, antibodies, and enzymatic assays have facilitated a
      huge body of work, which continues to unravel the fascinating biology of PTEN.

PMID- 27033068
TI  - Immunopathologic Assessment of PTEN Expression.
AB  - Immunohistochemistry (IHC) is an excellent technique used routinely to define the
      phenotype in pathology laboratories through the analysis of molecular expression
      in cells and tissues. The PTEN protein is ubiquitously expressed in the majority
      of human tissues, and allelic or complete loss of PTEN is frequently observed in
      different types of malignancies leading to an activation of the AKT/mTOR
      pathways. IHC-based analyses are best to determine the level of PTEN expression
      in histological samples, but not to assess partial or heterozygous deletions, for
      which FISH analyses are more appropriate. Interpretation of the IHC results is
      the most critical point in the assessment of PTEN expression, since it is used
      both as a prognostic factor and as a tool to guide therapeutic intervention and
      response to therapy. Importantly, analyses of well-known downstream markers, such
      as AKT or mTOR, may be used to further analyze PTEN functional status.

PMID- 27033069
TI  - Measurement of PTEN by Flow Cytometry.
AB  - Recent advancements have driven the development of smaller footprint, less
      expensive, and user-friendly flow cytometers introducing the technology to more
      users.Flow cytometry is an established tool for multiparametric analysis of
      various important cellular characteristics. Fluorescent dyes or fluorophore
      conjugated antibodies allow for measurement of protein expression, identification
      of cell populations, or DNA content analysis. This is combined with analysis of
      light-scattering detection to determine cell size and complexity to allow for the
      study of complex cell samples, such as whole blood. Through antibody staining for
      a variety of surface markers as well as intracellular proteins we can also
      elucidate intracellular signaling, and phosphor-signaling, on a single-cell
      basis.Here we describe the application of flow cytometry analysis to the tumor
      suppressor PTEN in various cancer cell lines and a mouse model. 

PMID- 27033070
TI  - Detecting PTEN and PI3K Signaling in Brain.
AB  - The central nervous system is comprised of multiple cell types including neurons,
      glia, and other supporting cells that may differ dramatically in levels of
      signaling pathway activation. Immunohistochemistry in conjunction with drug
      interference are powerful tools that allow evaluation of signaling pathways in
      different cell types of the mouse central nervous system in vivo. Here we provide
      detailed protocols for immunohistochemistry to evaluate three essential
      components in the PI3K pathway in mouse brain: Pten, p-Akt, and p-4ebp1, and for
      rapamycin treatment to modulate mTOR signaling in vivo.

PMID- 27033071
TI  - Germline PTEN Mutation Analysis for PTEN Hamartoma Tumor Syndrome.
AB  - Clinically, deregulation of PTEN function resulting in reduced PTEN expression
      and/or activity is implicated in human disease. Cowden syndrome (CS) is an
      autosomal dominant disorder characterized by benign and malignant tumors. CS
      related individual features occur commonly in the general population.
      Approximately 25 % of patients diagnosed with CS have pathogenic germline PTEN
      mutations, which increase lifetime risks of breast, thyroid, uterine, renal, and
      other cancers. PTEN testing and intensive cancer surveillance allow for early
      detection and treatment of these cancers for mutation-positive patients and their
      relatives. In this methods chapter, we highlight our protocol for identifying
      patients at risk of harboring a germline PTEN mutation. 

PMID- 27033072
TI  - Methods for Assessing the In Vivo Role of PTEN in Glucose Homeostasis.
AB  - PTEN plays an important role in diabetes pathogenesis not only as a key negative
      regulator of the PI3K/Akt pathway required for insulin action, but also via its
      role in other cell processes required to maintain metabolic homeostasis. We
      describe the generation of tissue-specific PTEN knockout mice and models of both
      type 1 and type 2 diabetes, which we have found useful for the study of diabetes
      pathogenesis. We also outline common methods suitable for the characterization of
      glucose homeostasis in rodent models, including techniques to measure beta cell
      function and insulin sensitivity.

PMID- 27033073
TI  - Rapid Detection of Dynamic PTEN Regulation in Living Cells Using Intramolecular
      BRET.
AB  - Tumor suppressor PTEN phosphatase acts to inhibit the PI3K/AKT pathway and thus
      regulates cell proliferation, survival, and migration. Dysregulation of PTEN
      function is observed in a wide range of cancers. In addition to alterations of
      the PTEN gene, repression of PTEN function can also occur at the protein level
      through changes in PTEN conformation, localization, activity, and stability. The
      ability to follow switches in PTEN conformation in live cells provides a rapid
      approach to study changes in PTEN function and may provide a basis to screen
      pharmacological agents aimed at enhancing or reestablishing PTEN-dependent
      signaling pathways that have gone awry in cancer. Here, we describe methods to
      use an intramolecular bioluminescent resonance energy transfer (BRET)-based
      biosensor that reports dynamic signal-dependent changes in PTEN conformational
      rearrangement and function.

PMID- 27033074
TI  - Methods for the Identification of PTEN-Targeting MicroRNAs.
AB  - The identification of PTEN-targeting microRNAs usually starts from an in silico
      bioinformatic prediction and then requires a careful experimental validation that
      exploits both heterologous and endogenous systems. Here we describe the methods
      used to carry on these analyses and experiments, examining pitfalls and
      alternatives for each step. Moreover, we give an overview of the latest high
      throughput microRNA target identification techniques which offer a more
      comprehensive view of the microRNAs that can bind a fundamental tumor suppressor
      such as PTEN. 

PMID- 27033075
TI  - Posttranscriptional Regulation of PTEN by Competing Endogenous RNAs.
AB  - PTEN expression can be dysregulated in cancers via multiple mechanisms including
      genomic loss, epigenetic silencing, transcriptional repression, and
      posttranscriptional regulation by microRNAs. MicroRNAs are short, noncoding RNAs
      that regulate gene expression by binding to recognition sites on target
      transcripts. Recent studies have demonstrated that the competition for shared
      microRNAs between both protein-coding and noncoding transcripts represents an
      additional facet of gene regulation. Here, we describe in detail an integrated
      computational and experimental approach to identify and validate these competing
      endogenous RNA (ceRNA) interactions. 

PMID- 27033076
TI  - In Cell and In Vitro Assays to Measure PTEN Ubiquitination.
AB  - The lipid and protein tyrosine phosphatase, PTEN, is one of the most frequently
      mutated tumor suppressors in human cancers and is essential for regulating the
      oncogenic pro-survival PI3K/AKT signaling pathway. Because of its diverse
      physiological functions, PTEN has attracted great interest from researchers in
      multiple research fields. The functional diversity of PTEN demands a collection
      of delicate regulatory mechanisms, including transcriptional control and
      posttranslational mechanisms that include ubiquitination. Addition of ubiquitin
      to PTEN can have several effects on PTEN function, potentially regulating its
      stability, localization, and activity. In cell and in vitro ubiquitination assays
      are employed to study the ubiquitination-mediated regulation of PTEN. However,
      PTEN ubiquitination assays are challenging to perform and the data published from
      these assays has been of mixed quality. Here we describe protocols to detect PTEN
      ubiquitination in cultured cells expressing epitope tagged ubiquitin (in cell
      PTEN ubiquitination assay) and also using purified proteins (in vitro PTEN
      ubiquitination assay). 

PMID- 27033077
TI  - Assessing PTEN Subcellular Localization.
AB  - PTEN subcellular localization is fundamental in the execution of the distinct
      PTEN biological activities, including not only its PI(3,4,5)P3 phosphatase
      activity when associated to membranes but also its subcellular compartment
      specific interactions with regulatory and effector proteins, including those
      exerted in the nucleus. As a consequence, PTEN subcellular localization is
      tightly regulated in vivo by both intrinsic and extrinsic mechanisms. The plasma
      membrane/nucleus/cytoplasm partitioning of PTEN has been the focus of several
      studies, both from a mechanistic and from a disease-association point of view.
      Here, we summarize the current knowledge on PTEN plasma
      membrane/nucleus/cytoplasm distribution, and present subcellular fractionation,
      immunofluorescence, and immunohistochemical methods to study the distribution and
      shuttling of PTEN between these subcellular compartments. 

PMID- 27033078
TI  - Methods to Study PTEN in Mitochondria and Endoplasmic Reticulum.
AB  - Although PTEN has been widely described as a nuclear and cytosolic protein, in
      the last 2 years, alternative organelles, such as the endoplasmic reticulum (ER),
      pure mitochondria, and mitochondria-associated membranes (MAMs), have been
      recognized as pivotal targets of PTEN activity.Here, we describe different
      methods that have been used to highlight PTEN subcellular localization.First, a
      protocol to extract nuclear and cytosolic fractions has been described to assess
      the "canonical" PTEN localization. Moreover, we describe a protocol for
      mitochondria isolation with proteinase K (PK) to further discriminate whether
      PTEN associates with the outer mitochondrial membrane (OMM) or resides within the
      mitochondria. Finally, we focus our attention on a subcellular fractionation
      protocol of cells that permits the isolation of MAMs containing unique regions of
      ER membranes attached to the outer mitochondrial membrane (OMM) and mitochondria
      without contamination from other organelles. In addition to biochemical
      fractionations, immunostaining can be used to determine the subcellular
      localization of proteins; thus, a detailed protocol to obtain good
      immunofluorescence (IF) is described. The employment of these methodological
      approaches could facilitate the identification of different PTEN localizations in
      several physiopathological contexts.

PMID- 27033079
TI  - Methods in the Study of PTEN Structure: X-Ray Crystallography and Hydrogen
      Deuterium Exchange Mass Spectrometry.
AB  - Despite its small size and deceptively simple domain organization, PTEN remains a
      challenging structural target due to its N- and C-terminal intrinsically
      disordered segments, and the conformational heterogeneity caused by
      phosphorylation of its C terminus. Using hydrogen/deuterium exchange mass
      spectrometry (HDX-MS), it is possible to probe the conformational dynamics of the
      disordered termini, and also to determine how PTEN binds to lipid membranes.
      Here, we describe how to purify recombinant, homogenously dephosphorylated PTEN
      from a eukaryotic system for subsequent investigation with HDX-MS or
      crystallography. 

PMID- 27033080
TI  - Methods for PTEN in Stem Cells and Cancer Stem Cells.
AB  - PTEN (phosphatase and tensin homologue) is the first tumor suppressor identified
      to have phosphatase activity and its gene is the second most frequently deleted
      or mutated tumor-suppressor gene associated with human cancers. Germline PTEN
      mutations are the cause of three inherited autosomal dominant disorders.
      Phosphatidylinositol 3,4,5,-triphosphate (PIP3), the product of the PI3 kinase,
      is one of the key intracellular targets of PTEN's phosphatase activity, although
      PTEN's phosphatase-independent activities have also been identified. PTEN is
      critical for stem cell maintenance, which contributes to its controlled
      tumorigenesis. PTEN loss leads the development of cancer stem cells (CSCs) that
      share properties with somatic stem cells, including the capacity for self-renewal
      and multi-lineage differentiation. Methods to isolate and functionally test stem
      cells and CSCs are important for understanding PTEN functions and the development
      of therapeutic approaches to target CSCs without having adverse effects on normal
      stem cells. Here, we describe protocols for the isolation and functional analysis
      of PTEN deficient embryonic stem cells, hematopoietic stem cells and leukemia
      initiating cells (LICs), neural stem cells, and prostate stem cells and CSCs.

PMID- 27033081
TI  - Modeling Cancer-Associated Mutations of PTEN in Mice.
AB  - Manipulation of mammalian genome and generation of genetically engineered mouse
      models (GEMMs) has revolutionized the scientific approach to address biological
      questions. To date, a number of gene-targeting strategies have been devised and
      are available to investigators for the generation of genetically modified mouse
      lines. Nevertheless, irrespective of the methodological approach selected, there
      remain critical molecular steps that need to be performed and put in place in
      order to obtain controlled and well-characterized new animal models. Here we
      provide technical details for the (1) handling and maintenance of mouse embryonic
      stem (ES) cells; (2) analysis of genomic DNA by Southern Blot; and (3) sequencing
      and PCR analysis of recombined genomic DNA. These experimental steps have been
      undertaken for the generation of new mouse models harboring cancer-associated
      PTEN mutations. 

PMID- 27033082
TI  - C. elegans Methods to Study PTEN.
AB  - C. elegans encodes a PTEN homolog called DAF-18 and human PTEN can functionally
      replace DAF-18. Thus C. elegans provides a valuable model organism to study PTEN.
      This chapter provides methods to study DAF-18/PTEN function in C. elegans. We
      provide methods to genotype daf-18/Pten mutants, visualize and quantify DAF
      18/PTEN in C. elegans, as well as to study physiological and developmental
      processes that will provide molecular insight on DAF-18/PTEN function. 

PMID- 27033083
TI  - How can a ureteral stone cause pain without hydronephrosis?

PMID- 27033084
TI  - Endoscopic description of renal papillary abnormalities in stone disease by
      flexible ureteroscopy: a proposed classification of severity and type.
AB  - INTRODUCTION: The goal of this original work was to describe papillary
      abnormalities using flexible ureteroscopy into a new classification and to assess
      their relation with stone composition. PATIENTS AND METHODS: We performed a
      prospective monocentric single-operator study aiming to describe various aspects
      of renal papillae. Data have been prospectively collected during consecutive 164
      sequential flexible ureterorenoscopies required for the treatment of renal stones
      from May 2011 to March 2015. The collected stones have been examined by
      microscopy and infrared spectrometry. Serum and urine biochemical samples have
      been systematically analyzed. RESULTS: A total of 74 patients (45.1 %) had renal
      papillary abnormalities on at least one papilla, excluding typical Randall's
      deposits alone. Various abnormalities were reported, some of them being present
      in the same patient: tip papillary erosions (51.3 %), anchored papillae calculi
      (47.3 %), subepithelial stones (18.9 %), cryptic papillae (10.8 %), extrophic
      papillae (9.46 %) and intraductal deposits (2.7 %). Associations between
      papillary abnormalities and stone types were found. Intraductal deposits were
      systematically associated with carbonate apatite IVa2 stones and hypocitraturia.
      A "first step" classification has been established to standardize the description
      of these papillary abnormalities for future reports and studies. CONCLUSIONS:
      This study highlights the necessity of papillary abnormalities description in
      further multicentric studies and ureteroscopy's reports. The established
      classification needs multicentric evaluation and validation. The endoscopic
      observation and knowledge of pathological aspects of the papillae should help to
      better understand pathogenesis of nephrolithiasis. Medical or surgical treatments
      of some abnormalities should be also discussed and evaluated to improve the
      prevention of stone recurrence.

PMID- 27033085
TI  - Basic Geriatrics Knowledge Among Internal Medicine Trainees in a Teaching
      Hospital in Saudi Arabia.
AB  - To assess the basic knowledge of medical trainees, in the absence of a structured
      geriatrics curriculum, around a variety of geriatric medicine components that are
      considered essential for the care of the rapidly increasing elderly population.
      Eighty-three trainees at different levels of training in internal medicine were
      asked about a variety of common geriatric conditions. Those included: delirium,
      falls, geriatric syndromes, pain, cognitive impairment, and medications. The
      trainees' knowledge about common geriatric condition was overall poor. The most
      pronounced deficits included: the lack of familiarity in diagnosing geriatric
      syndromes (63 %) or managing them (67 %), the underestimation of the prevalence
      of delirium (49 %), and the tendency to undertreat pain (64 %). Poor familiarity
      with polypharmacy and its impact, as well as inappropriate prescription practices
      in the elderly were also observed. In the absence of a structured geriatric
      medicine curriculum, internal medicine trainees' knowledge about important
      geriatric conditions is poor, even if their internal medicine knowledge is
      overall adequate. This would translate into suboptimal care for this vulnerable
      and rapidly expanding segment of the population. 

PMID- 27033086
TI  - Induced Loudness Reduction and Enhancement in Acoustic and Electric Hearing.
AB  - The loudness of a tone can be reduced by preceding it with a more intense tone.
      This effect, known as induced loudness reduction (ILR), has been reported to last
      for several seconds. The underlying neural mechanisms are unknown. One possible
      contributor to the effect involves changes in cochlear gain via the medial
      olivocochlear (MOC) efferents. Since cochlear implants (CIs) bypass the cochlea,
      investigating whether and how CI users experience ILR should help provide a
      better understanding of the underlying mechanisms. In the present study, ILR was
      examined in both normal-hearing listeners and CI users by examining the effects
      of an intense precursor (50 or 500 ms) on the loudness of a 50-ms target, as
      judged by comparing it to a spectrally remote 50-ms comparison sound. The
      interstimulus interval (ISI) between the precursor and the target was varied
      between 10 and 1000 ms to estimate the time course of ILR. In general, the
      patterns of results from the CI users were similar to those found in the normal
      hearing listeners. However, in the short-precursor short-ISI condition, an
      enhancement in the loudness of target was observed in CI subjects that was not
      present in the normal-hearing listeners, consistent with the effects of an
      additional attenuation present in the normal-hearing listeners but not in the CI
      users. The results suggest that the MOC may play a role but that it is not the
      only source of these loudness context effects.

PMID- 27033087
TI  - Six Degrees of Auditory Spatial Separation.
AB  - The location of a sound is derived computationally from acoustical cues rather
      than being inherent in the topography of the input signal, as in vision. Since
      Lord Rayleigh, the descriptions of that representation have swung between
      "labeled line" and "opponent process" models. Employing a simple variant of a two
      point separation judgment using concurrent speech sounds, we found that spatial
      discrimination thresholds changed nonmonotonically as a function of the overall
      separation. Rather than increasing with separation, spatial discrimination
      thresholds first declined as two-point separation increased before reaching a
      turning point and increasing thereafter with further separation. This "dipper"
      function, with a minimum at 6  degrees  of separation, was seen for regions
      around the midline as well as for more lateral regions (30 and 45  degrees ). The
      discrimination thresholds for the binaural localization cues were linear over the
      same range, so these cannot explain the shape of these functions. These data and
      a simple computational model indicate that the perception of auditory space
      involves a local code or multichannel mapping emerging subsequent to the binaural
      cue coding.

PMID- 27033088
TI  - Applying Nanoscale Kirkendall Diffusion for Template-Free, Kilogram-Scale
      Production of SnO2 Hollow Nanospheres via Spray Drying System.
AB  - A commercially applicable and simple process for the preparation of aggregation
      free metal oxide hollow nanospheres is developed by applying nanoscale Kirkendall
      diffusion to a large-scale spray drying process. The precursor powders prepared
      by spray drying are transformed into homogeneous metal oxide hollow nanospheres
      through a simple post-treatment process. Aggregation-free SnO2 hollow nanospheres
      are selected as the first target material for lithium ion storage applications.
      Amorphous carbon microspheres with uniformly dispersed Sn metal nanopowder are
      prepared in the first step of the post-treatment process under a reducing
      atmosphere. The post-treatment of the Sn-C composite powder at 500  degrees C
      under an air atmosphere produces carbon- and aggregation-free SnO2 hollow
      nanospheres through nanoscale Kirkendall diffusion. The hollow and filled SnO2
      nanopowders exhibit different cycling performances, with their discharge
      capacities after 300 cycles being 643 and 280 mA h g(-1), respectively, at a
      current density of 2 A g(-1). The SnO2 hollow nanospheres with high structural
      stability exhibit superior cycling and rate performances for lithium ion storage
      compared to the filled ones. 

PMID- 27033089
TI  - Quercetin-3-O-rhamnoside from Euphorbia hirta protects against snake Venom
      induced toxicity.
AB  - BACKGROUND: The plant Euphorbia hirta is widely used against snake envenomations
      in rural areas and it was proved to be effective in animal models. Therefore, the
      scientific validation of its phytoconstituents for their antiophidian activity is
      aimed in the present study. METHODS: E. hirta extract was subjected to
      bioactivity guided fractionation and the fractions that inhibited different
      enzyme activities of Naja naja venom in vitro was structurally characterized
      using UV, FT-IR, LC-MS and NMR spectroscopy. Edema, hemorrhage and lethality
      inhibition activity of the compound were studied in mice model. In addition,
      molecular docking and molecular dynamic simulations were also performed in
      silico. RESULTS: The bioactive fraction was identified as Quercetin-3-O-alpha
      rhamnoside (QR, 448.38 Da). In vitro experiments indicated that protease,
      phospholipase-A(2), hemolytic activity and hemorrhage inducing activity of the
      venom were inhibited completely at a ratio of 1:20 (venom: QR) w/w. At the same
      concentration, the edema ratio was drastically reduced from 187% to 107%.
      Significant inhibition (93%) of hyaluronidase activity was also observed at a
      slightly higher concentration of QR (1:50). Further, in in vivo analysis, QR
      significantly prolonged the survival time of mice injected with snake venom.
      CONCLUSION: For the first time Quercetin-3-O-alpha-rhamnoside, isolated from E.
      hirta, has been shown to exhibit anti-snake venom activity against Naja naja
      venom induced toxicity. GENERAL SIGNIFICANCE: Exploring such multifunctional lead
      molecules with anti-venom activity would help in developing complementary
      medicine for snakebite treatments especially in rural areas where anti-snake
      venom is not readily available.

PMID- 27033090
TI  - Glycerol Dehydratases: Biochemical Structures, Catalytic Mechanisms, and
      Industrial Applications in 1,3-Propanediol Production by Naturally Occurring and
      Genetically Engineered Bacterial Strains.
AB  - To date, two types of glycerol dehydratases have been reported: coenzyme B12
      dependent and coenzyme B12-independent glycerol dehydratases. The three
      dimensional structure of the former is a dimer of alphabetagamma heterotrimer,
      while that of the latter is a homodimer. Their mechanisms of reaction are
      typically enzymatic radical catalysis. Functional radical in both the glycerol
      dehydratases is the adenosyl radical. However, the adenosyl radical in the former
      originates from coenzyme B12 by homolytic cleavage, and that in the latter from S
      adenosyl-methionine. Until some years ago, Clostridium butyricum VPI 1718 was the
      only microorganism known to possess B12-independent glycerol dehydratase, but
      since then, several other bacteria with this unique capability have been
      identified. This article focuses on the glycerol dehydratases and on 1,3
      propanediol production from glycerol by naturally occurring and genetically
      engineered bacterial strains containing glycerol dehydratase. 

PMID- 27033091
TI  - Covalent Immobilization and Characterization of a Novel Pullulanase from
      Fontibacillus sp. Strain DSHK 107 onto Florisil(r) and Nano-silica for Pullulan
      Hydrolysis.
AB  - A novel pullulanase partially purified from Fontibacillus sp. was covalently
      immobilized on Florisil(r) and nano-silica through both glutaraldehyde and (3
      glycidyloxypropyl)trimethoxysilane spacer arms. The pullulanase immobilized on
      Florisil(r) and nano-silica through glutaraldehyde spacer arm showed 85 and 190 %
      activity of its free form, respectively, whereas no activity was observed when it
      was immobilized on the same supports through (3
      glycidyloxypropyl)trimethoxysilane spacer arm. The maximum working pHs of both
      the immobilized pullulanases on Florisil(r) and nano-silica through
      glutaraldehyde spacer arm were determined as 5.0; however, the maximum working pH
      of the free pullulanase was pH 6.0. The maximum temperatures of all the
      pullulanase preparations were determined as 35  degrees C. The apparent K m
      values were 1.49, 1.54, and 0.59 mg/mL pullunan, respectively, for the free and
      immobilized pullulanases on Florisil(r) and nano-silica. The corresponding
      apparent V max values were 0.59, 1.53, and 1.57 U mg prot.(-1) min.(-1). Thermal
      stability of pullulanases immobilized on Florisil(r) and nano-silica was enhanced
      6.5- and 15.6-folds, respectively at 35  degrees C and 6.6- and 16.0-folds,
      respectively, at 50  degrees C. The pullulanases immobilized on Florisil(r) and
      nano-silica protected 71 and 90 % of their initial activities after 10 reuses. 

PMID- 27033092
TI  - Being paid relatively well most of the time: Negatively skewed payments are more
      satisfying.
AB  - How does the structure of a series of payments influence its recipient's
      satisfaction? A common hypothesis is that each payment will be compared with a
      single "standard" or "reference" payment (e.g., the average payment). Cognitive
      models of judgment such as range frequency theory predict in contrast that the
      entire payment distribution will influence evaluation of each individual payment.
      Two experiments examined satisfaction with a series of payments. In both
      experiments, most payments were either relatively high in the experienced
      distribution (the distribution was negatively skewed) or relatively low
      (positively skewed). The total and average payment was held constant. Experiment
      1 found that average satisfaction with individual payments was higher when the
      payments were negatively skewed, consistent with range frequency theory, and
      earlier findings were extended by comparing range frequency theory with a range
      based model, a rank-based model, and a reference point model at the individual
      level. Experiment 2 examined satisfaction with whole sequences of payments and
      found that receiving a negatively skewed sequence was more satisfying overall
      than receiving a positively skewed sequence. It is concluded that negatively
      skewed payment distributions are more satisfying, as predicted by cognitive
      models of judgment.

PMID- 27033093
TI  - Breast cancer risk in Chinese women with BRCA1 or BRCA2 mutations.
AB  - BRCA1/2 mutations represent approximately 5 % of unselected Chinese women with
      breast cancer. However, the breast cancer risk of Chinese women with BRCA1/2
      mutations is unknown. Therefore, the aim of this study was to estimate the age
      specific cumulative risk of breast cancer in Chinese women who carry a BRCA1 or
      BRCA2 mutation. Our study included 1816 unselected Chinese women with breast
      cancer and 5549 female first-degree relatives of these probands. All probands
      were screened for BRCA1/2 mutation. The age-specific cumulative risks of BRCA1/2
      carriers were estimated using the kin-cohort study by comparing the history of
      breast cancer in first-degree female relatives of BRCA1/2 carriers and non
      carriers. Among the 1816 probands, 125 BRCA1/2 pathogenic mutations were
      identified (70 in the BRCA1 gene and 55 in the BRCA2 gene). The incidence of
      breast cancer in the first-degree female relatives of BRCA1/2 mutation carriers
      was significantly higher (3.7-fold and 4.4-fold for BRCA1 and BRCA2 mutation
      carriers, respectively) than in non-carriers. The estimated cumulative risks of
      breast cancer by age 70 years were 37.9 % [95 % confidence interval (CI) 24.1
      54.4 %] for BRCA1 mutation carriers and 36.5 % (95 % CI 26.7-51.8 %) for BRCA2
      mutation carriers, respectively. Our study suggests that the breast cancer risk
      of Chinese women with BRCA1/2 mutations appears to be relatively high by the age
      of 70. Therefore, genetic counseling, enhanced surveillance, and individual
      preventive strategies should be provided for Chinese women who carry a BRCA1/2
      mutation.

PMID- 27033095
TI  - An unusual variation of carotid-vertebrobasilar arteries: An anatomical case
      report.
AB  - BACKGROUND AND PURPOSE: Having no obvious clinical symptoms and signs, it is
      difficult to find head and neck vascular variations without the aid of vascular
      imaging techniques. SUMMARY OF CASE: A 66-year-old female patient underwent head
      and neck computed tomographic angiography examination. Her computed tomographic
      angiography examination revealed that the internal carotid artery directly
      migrated to the ophthalmic artery. Brain blood supply is provided by the
      vertebrobasilar artery independently. CONCLUSION: To the best of the author's
      knowledge, this is a very rare anatomical vascular variation of the head and neck
      found by computed tomographic angiography.

PMID- 27033094
TI  - Bilateral transfer phenomenon: A functional magnetic resonance imaging pilot
      study of healthy subjects.
AB  - BACKGROUND: The bilateral transfer of a motor skill is a physiological
      phenomenon: the development of a motor skill with one hand can trigger the
      development of the same ability of the other hand. OBJECTIVE: The purpose of this
      study was to verify whether bilateral transfer is associated with a specific
      brain activation pattern using functional magnetic resonance imaging (fMRI).
      METHODS: The motor task was implemented as the execution of the Nine Hole Peg
      Test. Fifteen healthy subjects (10 right-handers and five left-handers) underwent
      two identical fMRI runs performing the motor task with the non-dominant hand.
      Between the first and the second run, each subject was intensively trained for
      five minutes to perform the same motor task with the dominant hand. RESULTS:
      Comparing the two functional scans across the pool of subjects, a change of the
      motor activation pattern was observed. In particular, we observed, in the second
      run, a change in the activation pattern both in the cerebellum and in the
      cerebral cortex. We found activations in cortical areas involved in somatosensory
      integration, areas involved in procedural memory. CONCLUSIONS: Our study shows,
      in a small group of healthy subjects, the modification of the fMRI activation
      pathway of a motor task performed by the non-dominant hand after intensive
      exercise performing the same task with the dominant hand.

PMID- 27033096
TI  - Graphitic Carbon-Coated FeSe2 Hollow Nanosphere-Decorated Reduced Graphene Oxide
      Hybrid Nanofibers as an Efficient Anode Material for Sodium Ion Batteries.
AB  - A novel one-dimensional nanohybrid comprised of conductive graphitic carbon (GC)
      coated hollow FeSe2 nanospheres decorating reduced graphene oxide (rGO) nanofiber
      (hollow nanosphere FeSe2@GC-rGO) was designed as an efficient anode material for
      sodium ion batteries and synthesized by introducing the nanoscale Kirkendall
      effect into the electrospinning method. The electrospun nanofibers transformed
      into hollow nanosphere FeSe2@GC-rGO hybrid nanofibers through a Fe@GC-rGO
      intermediate. The discharge capacities of the bare FeSe2 nanofibers, nanorod
      FeSe2-rGO-amorphous carbon (AC) hybrid nanofibers, and hollow nanosphere FeSe2@GC
      rGO hyrbid nanofibers at a current density of 1 A g(-1) for the 150th cycle were
      63, 302, and 412 mA h g(-1), respectively, and their corresponding capacity
      retentions measured from the 2nd cycle were 11, 73, and 82%, respectively. The
      hollow nanosphere FeSe2@GC-rGO hybrid nanofibers delivered a high discharge
      capacity of 352 mA h g(-1) even at an extremely high current density of 10 A g(
      1). The enhanced electrochemical properties of the hollow nanosphere FeSe2@GC-rGO
      composite nanofibers arose from the synergetic effects of the FeSe2 hollow
      morphology and highly conductive rGO matrix. 

PMID- 27033097
TI  - Oxidative and nitrosative stress pathways in the brain of socially isolated adult
      male rats demonstrating depressive- and anxiety-like symptoms.
AB  - Various stressors may disrupt the redox homeostasis of an organism by causing
      oxidative and nitrosative stress that may activate stressor-specific pathways and
      provoke specific responses. Chronic social isolation (CSIS) represents a mild
      chronic stress that evokes a variety of neurobehavioral changes in rats similar
      to those observed in people with psychiatric disorders, including depression.
      Most rodent studies have focused on the effect of social isolation during weaning
      or adolescence, while its effect in adult rats has not been extensively examined.
      In this review, we discuss the current knowledge regarding the involvement of
      oxidative/nitrosative stress pathways in the prefrontal cortex and hippocampus of
      adult male rats exposed to CSIS, focusing on hypothalamic-pituitary
      adrenocortical (HPA) axis activity, behavior parameters, antioxidative defense
      systems, stress signaling mediated by nuclear factor-kappa B (NF-kappaB), and
      mitochondria-related proapoptotic signaling. Although increased concentrations of
      corticosterone (CORT) have been shown to induce oxidative and nitrosative stress,
      we suggest a mechanism underlying the glucocorticoid paradox whereby a state of
      oxidative/nitrosative stress may exist under basal CORT levels. This review also
      highlights the differential susceptibility of prefrontal cortex and hippocampus
      to oxidative stress following CSIS and suggests a possible cellular pathway of
      stress tolerance that preserves the hippocampus from molecular damage and
      apoptosis. The differential regulation of the transcriptional factor NF-kappaB,
      and the enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX
      2) following CSIS may be one functional difference between the response of the
      prefrontal cortex and hippocampus, thus identifying potentially relevant targets
      for antidepressant treatment.

PMID- 27033098
TI  - Polynuclear Aromatic Hydrocarbons in Port Valdez Shrimp and Sediment.
AB  - Polynuclear aromatic hydrocarbons (PAHs) from oil were present in some shrimp
      from Port Valdez, site of a ballast water treatment facility at the Alyeska
      Alaska Marine Terminal (AMT). Low-level petrogenic PAH concentrations were
      generally restricted to shrimp eggs in the vicinity of the AMT and extended along
      the southern shore of Port Valdez to Anderson Bay. Eggs had greater lipid content
      than other tissues and thus were the most vulnerable biological compartment to
      hydrocarbon accumulation. Petrogenic hydrocarbons were not observed in shrimp
      muscle and cephalothoraxes; thus, these tissues do not pose a human health risk.
      Risk for children older than age 2 years and adults consuming eggs also was low
      except for two unusual samples (of 32), collected about 17 km west of the
      treatment facility. In general, PAH loads were consistent with local time series
      data in other species. We infer that the accumulation mechanism was dissolved
      uptake from water, consistent with passive sampler observations completed more
      than a decade earlier. Hydrocarbon levels in the majority of samples were below
      toxic thresholds. Total PAH accumulation was substantially greater in some pink
      shrimp than in other species, thus differences in habitat utilization (muddy vs.
      rocky substrate) are potentially important. 

PMID- 27033099
TI  - Effects of Endosulfan on Predator-Prey Interactions Between Catfish and
      Schistosoma Host Snails.
AB  - The effect of the pesticide endosulfan on predator-prey interactions between
      catfish and Schistosoma host snails was assessed in static tank experiments.
      Hybrid catfish (Clarias gariepinus * C. ngamensis) and Bulinus globosus were
      subjected to various endosulfan concentrations including an untreated control.
      The 48- and 96-h LC50 values for catfish were 1.0 and <0.5 ug/L, respectively,
      whereas the 48- and 96-h LC50 values for snails were 1137 and 810 ug/L. To assess
      sublethal effects on the feeding of the catfish on B. globosus, endosulfan
      concentrations between 0.03 and 1.0 ug/L were used. Predation was significantly
      greater (p < 0.001) in control tanks than in all other treatments. There was
      progressively decreasing predation with increasing toxicant concentration.
      Biological control of Schistosoma host snails using fish may be affected in
      endosulfan-polluted aquatic systems of Southern Africa because it has been found
      present at concentrations that are indicated to cause lethal effects on the
      evaluated hybrid catfish and to inhibit the predation of snails by this hybrid
      catfish. 

PMID- 27033100
TI  - Fetal abnormalities leading to termination of twin pregnancies: the 17-year
      experience of a single medical center.
AB  - OBJECTIVE: To assess fetal abnormalities leading to termination of pregnancy
      (TOP) performed in twin pregnancies. METHOD: The current study consisted of all
      women with dichorionic twin pregnancies (study group) who underwent TOP due to
      fetal abnormalities in our institute from 1999 to 2015. The data were compared to
      our registry of all parturient women with a singleton pregnancy (control group)
      that underwent TOP due to fetal anomalies at the same period. RESULTS: There were
      2495 cases of TOP because of fetal indications during the study period. Of them,
      86 (3.4%) and 2409 (96.6%) were from the study and control group, respectively.
      Structural anomalies were the leading indication for TOP in twins compared with
      singleton pregnancies (81.4% versus 50.9%, respectively, p < 0.0001). For twins,
      the leading indication for TOP was central nervous system (CNS) abnormalities and
      it was more common compared with singleton pregnancies (26.1% versus 12.2%,
      respectively, p < 0.0001). This was followed by chromosomal/genetic abnormalities
      (16.3% versus 40.4%, respectively, p < 0.0001). CONCLUSIONS: We found a different
      distribution for fetal anomalies leading to TOP in twins versus singleton
      pregnancies. The main indication for TOP in the study group was structural
      malformations, with a predominance of CNS abnormalities.

PMID- 27033101
TI  - The relationship between hyperhomocysteinemia and neurodegeneration.
AB  - Homocysteine (Hcy) is a key junction in methionine metabolism. In inherited forms
      of hyperhomocysteinemia patients develop early vascular damage and cognitive
      decline. Hyperhomocysteinemia is a common consequence of dietary, behavioral and
      pathological conditions and is epidemiologically related to different diseases,
      among them neurodegenerative ones are receiving progressively more attention in
      the last years. Several detrimental mechanisms that see in Hcy a possible
      promoter seem to be implicated in neurodegeneration (protein structural and
      functional modifications, oxidative stress, cellular metabolic derangements,
      epigenetic modifications, pathological aggregates deposition, endothelial damage
      and atherothrombosis). Interventional studies exploring B group vitamins
      administration in terms of prevention of Hcy-related cognitive decline and
      cerebrovascular involvement have shown scant results. In this review, current and
      possible alternative/complementary approaches are discussed. 

PMID- 27033102
TI  - Consolidation of regulation in Europe is needed for the ICMJE's data sharing
      proposal to work.

PMID- 27033103
TI  - DNA damage regulation and its role in drug-related phenotypes in the malaria
      parasites.
AB  - DNA of malaria parasites, Plasmodium falciparum, is subjected to extraordinary
      high levels of genotoxic insults during its complex life cycle within both the
      mosquito and human host. Accordingly, most of the components of DNA repair
      machinery are conserved in the parasite genome. Here, we investigated the genome
      wide responses of P. falciparum to DNA damaging agents and provided
      transcriptional evidence of the existence of the double strand break and excision
      repair system. We also showed that acetylation at H3K9, H4K8, and H3K56 play a
      role in the direct and indirect response to DNA damage induced by an alkylating
      agent, methyl methanesulphonate (MMS). Artemisinin, the first line antimalarial
      chemotherapeutics elicits a similar response compared to MMS which suggests its
      activity as a DNA damaging agent. Moreover, in contrast to the wild-type P.
      falciparum, two strains (Dd2 and W2) previously shown to exhibit a mutator
      phenotype, fail to induce their DNA repair upon MMS-induced DNA damage. Genome
      sequencing of the two mutator strains identified point mutations in 18 DNA repair
      genes which may contribute to this phenomenon. 

PMID- 27033105
TI  - US taskforce will push for parity in mental health and substance misuse
      treatment.

PMID- 27033104
TI  - p53 downregulates the Fanconi anaemia DNA repair pathway.
AB  - Germline mutations affecting telomere maintenance or DNA repair may,
      respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically
      related bone marrow failure syndromes. Mice expressing p53(Delta31), a mutant p53
      lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased
      p53 activity in p53(Delta31/Delta31) fibroblasts correlated with a decreased
      expression of 4 genes implicated in telomere syndromes. Here we show that these
      cells exhibit decreased mRNA levels for additional genes contributing to telomere
      metabolism, but also, surprisingly, for 12 genes mutated in Fanconi anaemia.
      Furthermore, p53(Delta31/Delta31) fibroblasts exhibit a reduced capacity to
      repair DNA interstrand crosslinks, a typical feature of Fanconi anaemia cells.
      Importantly, the p53-dependent downregulation of Fanc genes is largely conserved
      in human cells. Defective DNA repair is known to activate p53, but our results
      indicate that, conversely, an increased p53 activity may attenuate the Fanconi
      anaemia DNA repair pathway, defining a positive regulatory feedback loop. 

PMID- 27033106
TI  - Encouraging Parental Trust and Honesty to Promote Food Security for All Children.

PMID- 27033109
TI  - Zhang et al, Nebulized Hypertonic Saline for Acute Bronchiolitis: A Systematic
      Review. Pediatrics. 2015;136(4):687-701; doi:10.1542/peds.2015-1914.

PMID- 27033108
TI  - Author's Response: Re: Encouraging Parental Trust and Honesty to Promote Food
      Security for All Children.

PMID- 27033107
TI  - Role of p53, Mitochondrial DNA Deletions, and Paternal Age in Autism: A Case
      Control Study.
AB  - BACKGROUND: The tumor suppressor p53 responds to a variety of environmental
      stressors by regulating cell cycle arrest, apoptosis, senescence, DNA repair,
      bioenergetics and mitochondrial DNA (mtDNA) copy number maintenance.
      Developmental abnormalities have been reported in p53-deficient mice, and altered
      p53 and p53-associated pathways in autism (AU). Furthermore, via the Pten-p53
      crosstalk, Pten haploinsufficient-mice have autisticlike behavior accompanied by
      brain mitochondrial dysfunction with accumulation of mtDNA deletions. METHODS:
      mtDNA copy number and deletions, and p53 gene copy ratios were evaluated in
      peripheral blood monocytic cells from children aged 2-5 years with AU (n = 66),
      race-, gender-, and age-matched typically neurodeveloping children (n = 46), and
      both parents from each diagnostic group, recruited by the Childhood Autism Risk
      from Genes and Environment study at the University of California, Davis. RESULTS:
      mtDNA deletions and higher p53 gene copy ratios were more common in children with
      AU and their fathers. The incidence of mtDNA deletions in fathers of children
      with AU was increased 1.9-fold over fathers of typically neurodeveloping
      children, suggesting a role for deficient DNA repair capacity not driven by
      paternal age. Deletions in mtDNA and altered p53 gene copy ratios seem to result
      from genetics (children with severity scores >=8) and/or act in concert with
      environmental factors (children with 6-7 severity scores). CONCLUSIONS: Given pro
      and antioxidant activities of p53, and associations of genomic instability with
      disorders other than AU, our study suggests a link between DNA repair capacity,
      genomic instability in the 17p13.1 region influenced by environmental triggers,
      and AU diagnosis.

PMID- 27033110
TI  - McCormick et al. A Case of a Central Conducting Lymphatic Anomaly Responsive to
      Sirolimus. Pediatrics. 2016;137(1):e20152694.

PMID- 27033111
TI  - Whatever Happened to First Do No Harm?

PMID- 27033112
TI  - Reason and Autonomy.

PMID- 27033113
TI  - Mitochondrial Copy Number as a Biomarker for Autism?

PMID- 27033114
TI  - Rosen et al. Utility of Symptoms to Predict Treatment Outcomes in Obstructive
      Sleep Apnea Syndrome. Pediatrics. 2015;135(3):e662-671; doi:10.1542/peds.2014
      3099).

PMID- 27033115
TI  - [Existential questions prior to elective surgery. Survey in a preoperative
      anesthesia consultation service].
AB  - BACKGROUND: Existential questions concerning the limitation of treatment must be
      answered when a major complication occurs after an elective operation. In these
      situations, the patient himself/herself cannot be asked about his/her will.
      Therefore, medical professionals must attempt to determine the patient's presumed
      will either through an existing advance directive (AD) or by consulting with the
      patient's relatives. Only one-fifth of all patients create an AD in advance, and
      the relatives cannot always reliably reproduce the patient's presumed will. Thus,
      it is important to talk about issues such as do-not-resuscitate before a patient
      undergoes elective major surgery. However, such discussions may unsettle and
      frighten the patient. This study aimed to determine if patients are willing to
      talk about difficult questions such as resuscitation before major surgery. How
      many patients create an AD? Who should decide when patients themselves are no
      longer capable? OBJECTIVES: Between March 1 and October 30, 2014, patients who
      attended the preoperative anaesthesia consultation service received a one-page
      questionnaire. In addition to a few personal questions (e.g. sex, age, surgery,
      health status), the questionnaire included four questions that could be answered
      according to a four-point Likert scale, with a yes or no response, or a with a
      selection of answers. RESULTS: 272 men (45.5%) and 321 women (53.7%) with a mean
      age of 52.9 years (standard deviation: 17.8 years) completed a questionnaire. 312
      patients (52.2%) claimed to be healthy, while 116 patients (19.4%) observed a
      minimal health restriction. 125 patients (19.4%) suffered from a chronic illness
      that markedly (n = 108) or strongly (n = 17) limited daily life. More than three
      fourths of the respondents were very ready (377/63.0%) or ready (79
      patients/13.2%) to talk about the treatment of severe complications after an
      elective operation. 12.7% of the patients would rather not to talk about this
      topic (n = 47) or refused (n = 37). 58 patients (9.7%) checked the box "I do not
      know" or gave no answer. There was no significant difference between men and
      women (p = 0.58). The patient's state of health did not significantly affect the
      patient's willingness to talk (p = 0.61). 110 patients (18.4%) had already
      completed an AD. The probability of having an AD is highly dependent on the age
      and state of health. The likelihood of having one increases by 4% for each year
      of life, and in health-impaired patients it is 73% higher than in healthy ones.
      If the patient could no longer decide for himself/herself, the following options
      were selected from multiple possible answers: a relative decides (n = 272),
      discussing this with a physician prior to surgery (n = 212), previously created
      AD (n = 198), the treatment team decides (n = 28), I do not know/not (n = 48).
      CONCLUSIONS: Although the majority of the respondents were willing to talk about
      difficult issues before an operation, it remains unclear to what extent these
      results can be generalized. However, the results justify efforts to carefully
      inquire about and document the will of sick patients prior to major surgery. Both
      the treatment team and the relatives are relieved if the patient's will is known
      when difficult decisions have to be made.

PMID- 27033116
TI  - Prevention of gallbladder hypomotility via FATP2 inhibition protects from
      lithogenic diet-induced cholelithiasis.
AB  - Gallstone disease is a widespread disorder costing billions for annual treatment
      in the United States. The primary mechanisms underlying gallstone formation are
      biliary cholesterol supersaturation and gallbladder hypomotility. The relative
      contribution of these two processes has been difficult to dissect, as
      experimental lithogenic diets cause both bile supersaturation and alterations in
      gallbladder motility. Importantly, there is no mechanistic explanation for
      obesity as a major risk factor for cholelithiasis. We discovered that lithogenic
      diets induce ectopic triacylglycerol (TAG) accumulation, a major feature of
      obesity and a known muscle contraction impairing condition. We hypothesized that
      prevention of TAG accumulation in gallbladder walls may prevent gallbladder
      contractile dysfunction without impacting biliary cholesterol saturation. We
      utilized adeno-associated virus-mediated knock down of the long-chain fatty acid
      transporter 2 (FATP2; Slc27A2), which is highly expressed by gallbladder
      epithelial cells, to downregulate lithogenic diet-associated TAG accumulation.
      FATP2-knockdown significantly reduced gallbladder TAG, but did not affect key
      bile composition parameters. Importantly, measurements with force displacement
      transducers showed that contractile strength in FATP2-knockdown gallbladders was
      significantly greater than in control gallbladders following lithogenic diet
      administration, and the magnitude of this effect was sufficient to prevent the
      formation of gallstones. FATP2-driven fatty acid uptake and the subsequent TAG
      accumulation in gallbladder tissue plays a pivotal role in cholelithiasis, and
      prevention of this process can protect from gallstone formation, even in the
      context of supersaturated bile cholesterol levels, thus pointing to new treatment
      approaches and targets.

PMID- 27033117
TI  - High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate
      sodium-induced colon cancer.
AB  - High-fat-diet (HFD) consumption is associated with colon cancer risk. However,
      little is known about how the lipid composition of a HFD can influence
      prooncogenic processes. We examined the effects of three HFDs differing in the
      percentage of total calories from saturated fat (SF) (6, 12, and 24% of total
      caloric intake), but identical in total fat (40%), and a commercially available
      Western diet (26 and 41% saturated and total fat, respectively) on colon cancer
      development using the azoxymethane (AOM)/dextran sulfate sodium (DSS) murine
      model. A second dose-response experiment was performed using diets supplemented
      with the saturated-fatty-acid (SFA)-rich coconut oil. In experiment 1, we found
      an inverse association between SF content and tumor burden. Furthermore,
      increased SF content was associated with reduced inflammation, increased
      apoptosis, and decreased proliferation. The second dose-response experiment was
      performed to test whether this effect may be attributed to the SF content of the
      diets. Consistent with the initial experiment, we found that high SF content was
      protective, at least in male mice; there was a decrease in mortality in mice
      consuming the highest concentration of SFAs. To explore a potential mechanism for
      these findings, we examined colonic mucin 2 (Muc2) protein content and found that
      the HFDs with the highest SF content had the greatest concentration of Muc2. Our
      data suggest that high dietary SF is protective in the AOM/DSS model of colon
      cancer, which may be due, at least in part, to the ability of SF to maintain
      intestinal barrier integrity through increased colonic Muc2.

PMID- 27033119
TI  - Periodontal dysbiosis linked to periodontitis is associated with cardiometabolic
      adaptation to high-fat diet in mice.
AB  - Periodontitis and type 2 diabetes are connected pandemic diseases, and both are
      risk factors for cardiovascular complications. Nevertheless, the molecular
      factors relating these two chronic pathologies are poorly understood. We have
      shown that, in response to a long-term fat-enriched diet, mice present particular
      gut microbiota profiles related to three metabolic phenotypes: diabetic-resistant
      (DR), intermediate (Inter), and diabetic-sensitive (DS). Moreover, many studies
      suggest that a dysbiosis of periodontal microbiota could be associated with the
      incidence of metabolic and cardiac diseases. We investigated whether
      periodontitis together with the periodontal microbiota may also be associated
      with these different cardiometabolic phenotypes. We report that the severity of
      glucose intolerance is related to the severity of periodontitis and cardiac
      disorders. In detail, alveolar bone loss was more accentuated in DS than Inter,
      DR, and normal chow-fed mice. Molecular markers of periodontal inflammation, such
      as TNF-alpha and plasminogen activator inhibitor-1 mRNA levels, correlated
      positively with both alveolar bone loss and glycemic index. Furthermore, the
      periodontal microbiota of DR mice was dominated by the Streptococcaceae family of
      the phylum Firmicutes, whereas the periodontal microbiota of DS mice was
      characterized by increased Porphyromonadaceae and Prevotellaceae families.
      Moreover, in DS mice the periodontal microbiota was indicated by an abundance of
      the genera Prevotella and Tannerella, which are major periodontal pathogens.
      PICRUSt analysis of the periodontal microbiome highlighted that prenyltransferase
      pathways follow the cardiometabolic adaptation to a high-fat diet. Finally, DS
      mice displayed a worse cardiac phenotype, percentage of fractional shortening,
      heart rhythm, and left ventricle weight-to-tibia length ratio than Inter and DR
      mice. Together, our data show that periodontitis combined with particular
      periodontal microbiota and microbiome is associated with metabolic adaptation to
      a high-fat diet related to the severity of cardiometabolic alteration.

PMID- 27033120
TI  - New partners and phosphorylation sites of focal adhesion kinase identified by
      mass spectrometry.
AB  - The regulation of focal adhesion kinase (FAK) involves phosphorylation and
      multiple interactions with other signaling proteins. Some of these pathways are
      relevant for nervous system functions such as branching, axonal guidance, and
      plasticity. In this study, we screened mouse brain to identify FAK-interactive
      proteins and phosphorylatable residues as a first step to address the neuronal
      functions of this kinase. Using mass spectrometry analysis, we identified new
      phosphorylated sites (Thr 952, Thr 1048, and Ser 1049), which lie in the FAT
      domain; and putative new partners for FAK, which include cytoskeletal proteins
      such as drebrin and MAP 6, adhesion regulators such as neurabin-2 and plakophilin
      1, and synapse-associated proteins such as SynGAP and a NMDA receptor subunit.
      Our findings support the participation of brain-localized FAK in neuronal
      plasticity. 

PMID- 27033118
TI  - Src kinases play a novel dual role in acute pancreatitis affecting severity but
      no role in stimulated enzyme secretion.
AB  - In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the
      activation of several signaling cascades that are implicated in mediating
      cellular processes (growth, cytoskeletal changes, apoptosis). However, the role
      of SFKs in various physiological responses such as enzyme secretion or in
      pathophysiological processes such as acute pancreatitis is either controversial,
      unknown, or incompletely understood. To address this, in this study, we
      investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme
      release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro
      acute-pancreatitis-like changes induced by supramaximal COOH-terminal octapeptide
      of cholecystokinin (CCK). SFK involvement assessed using the chemical SFK
      inhibitor (PP2) with its inactive control, 4-amino-7-phenylpyrazol[3,4
      d]pyrimidine (PP3), under experimental conditions, markedly inhibiting SFK
      activation. In CCK-stimulated pancreatic acinar cells, activation occurred of
      trypsinogen, various MAP kinases (p42/44, JNK), transcription factors (signal
      transducer and activator of transcription-3, nuclear factor-kappaB, activator
      protein-1), caspases (3, 8, and 9) inducing apoptosis, LDH release reflective of
      necrosis, and various chemokines secreted (monocyte chemotactic protein-1,
      macrophage inflammatory protein-1alpha, regulated on activation, normal T cell
      expressed and secreted). All were inhibited by PP2, not by PP3, except caspase
      activation leading to apoptosis, which was increased, and trypsin activation,
      which was unaffected, as was CCK-induced amylase release. These results
      demonstrate SFK activation is playing a dual role in acute pancreatitis,
      inhibiting apoptosis and promoting necrosis as well as chemokine/cytokine release
      inducing inflammation, leading to more severe disease, as well as not affecting
      secretion. Thus, our studies indicate that SFK is a key mediator of inflammation
      and pancreatic acinar cell death in acute pancreatitis, suggesting it could be a
      potential therapeutic target in acute pancreatitis.

PMID- 27033121
TI  - Clinical Characteristics of Posterior Staphylomas in Myopic Eyes With Axial
      Length Shorter Than 26.5 Millimeters.

PMID- 27033122
TI  - Reply.

PMID- 27033123
TI  - Measurement of Foveal Avascular Zone Dimensions and its Reliability in Healthy
      Eyes Using Optical Coherence Tomography Angiography.

PMID- 27033124
TI  - Liver: Hepatocytes induced from myofibroblasts in vivo.

PMID- 27033125
TI  - Gut microbiota: Gut bacteria affect post-ischaemic inflammation in stroke by
      modulating intestinal T cells.

PMID- 27033127
TI  - Pancreatitis: NETs clog pancreatic ducts.

PMID- 27033128
TI  - Developmental biology: Liver vasculature cells are derived from cardiac tissue.

PMID- 27033126
TI  - Diagnosis and management of chronic constipation in adults.
AB  - Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute
      or transient constipation can be due to changes in diet, travel or stress, and
      secondary constipation can result from drug treatment, neurological or metabolic
      conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation
      is made after exclusion of secondary causes of constipation and encompasses
      several overlapping subtypes. Slow-transit constipation is characterized by
      prolonged colonic transit in the absence of pelvic floor dysfunction. This
      subtype of constipation can be identified using either the radio-opaque marker
      test or wireless motility capsule test, and is best treated with laxatives such
      as polyethylene glycol or newer agents such as linaclotide or lubiprostone. If
      unsuccessful, subspecialist referral should be considered. Dyssynergic defecation
      results from impaired coordination of rectoanal and pelvic floor muscles, and
      causes difficulty with defecation. The condition can be identified using
      anorectal manometry and balloon expulsion tests and is best managed with
      biofeedback therapy. Opioid-induced constipation is an emerging entity, and
      several drugs including naloxegol, methylnaltrexone and lubiprostone are approved
      for its treatment. In this Review, we provide an overview of the burden and
      pathophysiology of chronic constipation, as well as a detailed discussion of the
      available diagnostic tools and treatment options.

PMID- 27033130
TI  - Introduction to Interpersonal Synchronization.

PMID- 27033129
TI  - Therapy: Metformin protective against colorectal cancer?

PMID- 27033131
TI  - Movement Coordination in Psychotherapy: Synchrony of Hand Movements is Associated
      with Session Outcome. A Single-Case Study.
AB  - Previous work has shown that nonverbal behavior was associated with both session
      level outcome and global outcome in psychotherapy. Nonverbal synchrony--here the
      coordination between patient's and psychotherapist's movement behavior--is a
      facet of nonverbal behavior that has recently been studied with video-based
      motion energy analysis (MEA). The present study aimed to replicate and extend
      these findings by using direct acquisition of movement data. In a single-case
      analysis, we monitored patient's and therapist's hand movements with a high
      resolution accelerometric measurement system (Vitaport (r)). In addition to these
      behavioral data, both patient and therapist provided session-level ratings of
      various factors relevant to the psychotherapy process, which were assessed with
      post-session questionnaires. The patient-therapist coordination of hand
      movements, i.e. nonverbal synchrony, in (N = 27) sessions of this dyadic
      psychotherapy was positively associated with progress reported in post-session
      questionnaires. Sessions with good evaluations concerning the quality of
      therapeutic alliance were characterized by high movement coordination. Thus,
      accelerometric data of this therapy dyad confirmed previous findings gained
      through video analyses: The coordination of nonverbal behavior shown by patient
      and therapist was an indicator of beneficial processes occurring within sessions.
      This replication study showed that nonverbal synchrony embodies important aspects
      of the alliance. Its assessment and quantification may provide therapists
      important additional information on processes that usually occur outside
      conscious awareness, but that nevertheless influence core aspects of the therapy.

PMID- 27033132
TI  - Synchronization Analysis of Language and Physiology in Human Dyads.
AB  - We studied the synchronization dynamics of a therapist and patient during a
      psychotherapy session. This investigation was developed in order to explore a new
      possible perspective and methodology for studying the expression of emotions.
      More specifically, literature concerning synchronization of in-session non-verbal
      variables emphasises its positive correlation with empathy and therapeutic
      outcomes. We compared the dynamics of galvanic skin response (GSR) and linguistic
      prosody, chosen as indicators of emotional expression in different domains. We
      studied their synchronization through complementary methodologies: Recurrence
      Quantification Analysis (RQA) and Principal Component Analysis (PCA), Markov
      Transition Matrix (MTM) and Cross-Recurrence Quantification Analysis (CRQA). We
      investigated the nonlinearity of GSR in terms of self-similarity and power-law,
      as emerged in autocorrelation functions and signal variations. We considered time
      lagged correlations as a measure of dynamical systems' memory. This article
      concludes by highlighting the importance of a deeper study of all variables
      related to the psychotherapeutic process and their synchronization in order to
      extend our knowledge of general human dynamics. 

PMID- 27033133
TI  - Top-down (Prior Knowledge) and Bottom-up (Perceptual Modality) Influences on
      Spontaneous Interpersonal Synchronization.
AB  - Coordination with others is such a fundamental part of human activity that it can
      happen unintentionally. This unintentional coordination can manifest as
      synchronization and is observed in physical and human systems alike. We
      investigated the role of top-down influences (prior knowledge of the perceptual
      modality their partner is using) and bottom-up factors (perceptual modality
      combination) on spontaneous interpersonal synchronization. We examine this
      phenomena with respect to two different theoretical perspectives that differently
      emphasize top-down and bottom-up factors in interpersonal synchronization: joint
      action/shared cognition theories and ecological-interactive theories. In an
      empirical study twelve dyads performed a finger oscillation task while attending
      to each other's movements through either visual, auditory, or visual and auditory
      perceptual modalities. Half of the participants were given prior knowledge of
      their partner's perceptual capabilities for coordinating across these different
      perceptual modality combinations. We found that the effect of top-down influence
      depends on the perceptual modality combination between two individuals. When
      people used the same perceptual modalities, top-down influence resulted in less
      synchronization and when people used different perceptual modalities, top-down
      influence resulted in more synchronization. Furthermore, persistence in the
      change in behavior as a result of having perceptual information about each other
      ('social memory') was stronger when this top-down influence was present. 

PMID- 27033134
TI  - Physiological Synchronization in Emergency Response Teams: Subjective Workload,
      Drivers and Empaths.
AB  - Behavioral and physiological synchronization have important implications for work
      teams with regard to workload management, coordinated behavior and overall
      functioning. This study extended previous work on the nonlinear statistical
      structure of GSR series in dyads to larger teams and included subjective ratings
      of workload and contributions to problem solving. Eleven teams of 3 or 4 people
      played a series of six emergency response (ER) games against a single opponent.
      Seven of the groups worked under a time pressure instruction at the beginning of
      the first game. The other four groups were not given that instruction until the
      beginning of the fourth game. The optimal lag length for the teams, which
      appeared to be phase-locked, was substantially shorter than that obtained
      previously for loosely-coupled dyads. There was a complex nonlinear effect from
      the time pressure manipulation on the autocorrelation over time that reflected
      workload and fatigue dynamics that were operating. The R2 values for linear and
      nonlinear statistical models differed by less than .01. The average amount of
      influence from one ER team member to another was 4.5-4.7% of the variance in GSR
      readings. ER team members were classified as drivers and empaths, based on the
      autocorrelations and transfer influences to and from other players in the GSR
      time series. Empaths were rated by their peers as making more types of positive
      contributions to the problem solving discussions than others, and drivers
      received the lowest ratings. Larger Lyapunov exponents that were calculated from
      the GSR time series were positively correlated with individuals' ratings of
      subjective workload and were negatively correlated with leadership indicators.
      Several directions for further research are outlined. 

PMID- 27033135
TI  - Tracing Neurodynamic Information Flows during Teamwork.
AB  - The goal of this study was to evaluate different neurodynamic representations for
      their ability to describe the interactions of team members with each other and
      with the changing task. Electroencephalography (EEG) data streams were collected
      from six crew members of a submarine piloting and navigation team while they
      performed a required training simulation. A representation of neurodynamic
      organization was first generated by creating symbols every second that showed the
      EEG power levels of each crew member. The second-by-second expression of these
      symbols continuously varied with the changing task, and the magnitude, duration
      and frequency of these variations could be quantitated using a moving window of
      Shannon entropy over the symbol stream. These changes in neurodynamic
      organization (i.e. entropy) were seen in the alpha, beta and gamma EEG frequency
      bands. A representation of team members' synchrony was created by measuring the
      mutual information in the EEG power levels for fourteen dyad combinations. Mutual
      information was present in the gamma EEG band, and elevated levels were
      distributed throughout the task. These discrete periods of synchrony were poorly
      correlated at zero lag with either changes in the team's neurodynamic
      organization, or speech patterns. 

PMID- 27033136
TI  - Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional
      Cellular Automata.
AB  - Synchronization has a long history in physics where it refers to the phase
      matching of two identical oscillators. This notion has been extensively studied
      in physics as well as in biology, where it has been applied to such widely
      varying phenomena as the flashing of fireflies and firing of neurons in the
      brain. Human behavior, however, may be recurrent but it is not oscillatory even
      though many physiological systems do exhibit oscillatory tendencies. Moreover,
      much of human behaviour is collaborative and cooperative, where the individual
      behaviours may be distinct yet contemporaneous (if not simultaneous) and taken
      collectively express some functionality. In the context of behaviour, the
      important aspect is the repeated co-occurrence in time of behaviours that
      facilitate the propagation of information or of functionality, regardless of
      whether or not these behaviours are similar or identical. An example of this
      weaker notion of synchronization is transient induced global response
      synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous
      phenomenon among complex systems, enabling them to stably parse environmental
      transients into salient units to which they stably respond. This leads to the
      notion of Sulis machines, which emergently generate a primitive linguistic
      structure through their dynamics. This article reviews the notion of TIGoRS and
      its expression in several complex systems models including tempered neural
      networks, driven cellular automata and cocktail party automata. The emergent
      linguistics of Sulis machines are discussed. A new class of complex systems
      model, the dispositional cellular automaton is introduced. A new metric for
      TIGoRS, the excess synchronization, is introduced and applied to the study of
      TIGoRS in dispositional cellular automata. It is shown that these automata
      exhibit a nonlinear synchronization response to certain perturbing transients. 

PMID- 27033137
TI  - A case of refractory eosinophilic fasciitis with eosinophilic vasculitis.

PMID- 27033138
TI  - Limiting the Number of Lumens in Peripherally Inserted Central Catheters to
      Improve Outcomes and Reduce Cost: A Simulation Study.
AB  - BACKGROUND The number of peripherally inserted central catheter (PICC) lumens is
      associated with thrombotic and infectious complications. Because multilumen PICCs
      are not necessary in all patients, policies that limit their use may improve
      safety and cost. OBJECTIVE To design a simulation-based analysis to estimate
      outcomes and cost associated with a policy that encourages single-lumen PICC use.
      METHODS Model inputs, including risk of complications and costs associated with
      single- and multilumen PICCs, were obtained from available literature and a
      multihospital collaborative quality improvement project. Cost savings and
      reduction in central line-associated bloodstream infection and deep vein
      thrombosis events from institution of a single-lumen PICC default policy were
      reported. RESULTS According to our model, a hospital that places 1,000 PICCs per
      year (25% of which are single-lumen and 75% multilumen) experiences annual PICC
      related maintenance and complication costs of $1,228,598 (95% CI, $1,053,175
      $1,430,958). In such facilities, every 5% increase in single-lumen PICC use would
      prevent 0.5 PICC-related central line-associated bloodstream infections and 0.5
      PICC-related deep vein thrombosis events, while saving $23,500. Moving from 25%
      to 50% single-lumen PICC utilization would result in total savings of $119,283
      (95% CI, $74,030-$184,170) per year. Regardless of baseline prevalence, a single
      lumen default PICC policy would be associated with approximately 10% cost
      savings. Findings remained robust in multiway sensitivity analyses. CONCLUSION
      Hospital policies that limit the number of PICC lumens may enhance patient safety
      and reduce healthcare costs. Studies measuring intended and unintended
      consequences of this approach, followed by rapid adoption, appear necessary.
      Infect Control Hosp Epidemiol 2016;37:811-817.

PMID- 27033139
TI  - Possible mast cell activation syndrome in a patient undergoing long-term
      hemodialysis.

PMID- 27033140
TI  - The Open Payments Program and the Emergency Physician.

PMID- 27033141
TI  - Examining Reliability and Validity of an Online Score (ALiEM AIR) for Rating Free
      Open Access Medical Education Resources.
AB  - STUDY OBJECTIVE: Since 2014, Academic Life in Emergency Medicine (ALiEM) has used
      the Approved Instructional Resources (AIR) score to critically appraise online
      content. The primary goals of this study are to determine the interrater
      reliability (IRR) of the ALiEM AIR rating score and determine its correlation
      with expert educator gestalt. We also determine the minimum number of educator
      raters needed to achieve acceptable reliability. METHODS: Eight educators each
      rated 83 online educational posts with the ALiEM AIR scale. Items include
      accuracy, usage of evidence-based medicine, referencing, utility, and the Best
      Evidence in Emergency Medicine rating score. A generalizability study was
      conducted to determine IRR and rating variance contributions of facets such as
      rater, blogs, posts, and topic. A randomized selection of 40 blog posts
      previously rated through ALiEM AIR was then rated again by a blinded group of
      expert medical educators according to their gestalt. Their gestalt impression was
      subsequently correlated with the ALiEM AIR score. RESULTS: The IRR for the ALiEM
      AIR rating scale was 0.81 during the 6-month pilot period. Decision studies
      showed that at least 9 raters were required to achieve this reliability. Spearman
      correlations between mean AIR score and the mean expert gestalt ratings were 0.40
      for recommendation for learners and 0.35 for their colleagues. CONCLUSION: The
      ALiEM AIR scale is a moderately to highly reliable, 5-question tool when used by
      medical educators for rating online resources. The score displays a fair
      correlation with expert educator gestalt in regard to the quality of the
      resources. The score displays a fair correlation with educator gestalt.

PMID- 27033142
TI  - The Association Between Limited English Proficiency and Unplanned Emergency
      Department Revisit Within 72 Hours.
AB  - STUDY OBJECTIVE: Language barriers are known to negatively affect many health
      outcomes among limited English proficiency patient populations, but little is
      known about the quality of care such patients receive in the emergency department
      (ED). This study seeks to determine whether limited English proficiency patients
      experience different quality of care than English-speaking patients in the ED,
      using unplanned revisit within 72 hours as a surrogate quality indicator.
      METHODS: We conducted a retrospective cohort study in an urban adult ED in 2012,
      with a total of 41,772 patients and 56,821 ED visits. We compared 2,943 limited
      English proficiency patients with 38,829 English-speaking patients presenting to
      the ED after excluding patients with psychiatric complaints, altered mental
      status, and nonverbal states, and those with more than 4 ED visits in 12 months.
      Two main outcomes-the risk of inpatient admission from the ED and risk of
      unplanned ED revisit within 72 hours-were measured with odds ratios from
      generalized estimating equation multivariate models. RESULTS: Limited English
      proficiency patients were more likely than English speakers to be admitted (32.0%
      versus 27.2%; odds ratio [OR]=1.20; 95% confidence interval [CI] 1.11 to 1.30).
      This association became nonsignificant after adjustments (OR=1.04; 95% CI 0.95 to
      1.15). Included in the analysis of ED revisit within 72 hours were 32,857
      patients with 45,546 ED visits; 4.2% of all patients (n=1,380) had at least 1
      unplanned revisit. Limited English proficiency patients were more likely than
      English speakers to have an unplanned revisit (5.0% versus 4.1%; OR=1.19; 95% CI
      1.02 to 1.45). This association persisted (OR=1.24; 95% CI 1.02 to 1.53) after
      adjustment for potential confounders, including insurance status. CONCLUSION: We
      found no difference in hospital admission rates between limited English
      proficiency patients and English-speaking patients. Yet limited English
      proficiency patients were 24% more likely to have an unplanned ED revisit within
      72 hours, with an absolute difference of 0.9%, suggesting challenges in ED
      quality of care.

PMID- 27033143
TI  - Saving Lives and Protecting People From Injuries and Violence.
AB  - Emergency physicians witness the effects of injury and violence every day.
      Traumatic brain injury, assault-related trauma, motor vehicle crashes, and opioid
      overdoses make up only some of these injuries-many of which can be prevented and
      better understood. The Centers for Disease Control and Prevention's National
      Center for Injury Prevention and Control (Injury Center) is uniquely poised to
      measure the toll of injury and violence on the lives of Americans, to communicate
      this public health burden, and to reduce the factors that increase their risk.
      Injury is the leading cause of death for persons aged 1 to 44 years in the United
      States. The Injury Center seeks to prevent violence and injuries and to reduce
      their consequences. For more than 20 years, Injury Center researchers have
      investigated factors that put Americans at risk through surveillance and research
      and translated these findings into evidence-based strategies and interventions.
      Many of these efforts are directly relevant to emergency medicine through
      preventing injuries and violence to save lives.

PMID- 27033144
TI  - Per-oral endoscopic myotomy (with video).

PMID- 27033145
TI  - Photo-activation of d(0) niobium imido azides: en route to nitrido complexes.
AB  - We report the synthesis and photo-reactivity of d(0) niobium imido azido
      complexes supported by beta-diketiminate ligands, which leads to the
      unprecedented formation of nitrides through a photo-assisted intramolecular
      rearrangement. This provides a new entry to metal nitrides that does not require
      low-valent metal centers and is a rare example in which the metal-imido moiety in
      group 5 complexes participates in reactivity. 

PMID- 27033146
TI  - Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical
      efficacy.
AB  - The scope of this review focuses on recent applications in preclinical and
      clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early
      detection and responses to therapy in animal models of Alzheimer's disease (AD).
      Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging
      Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD
      imaging has been to assess changes in brain anatomy, specifically assessing brain
      shrinkage and regional changes in white matter tractography using diffusion
      tensor imaging. However, advances in MRI have led to multiple efforts toward
      imaging amyloid beta plaques first without and then with the use of MRI contrast
      agents. These technological advancements have met with limited success and are
      not yet appropriate for the clinic. Recent developments in molecular imaging
      inclusive of high-power liposomal-based MRI contrast agents as well as fluorine
      19 ((19)F) MRI and manganese enhanced MRI have begun to propel promising advances
      toward not only plaque imaging but also using MRI to detect perturbations in
      subcellular processes occurring within the neuron. This review concludes with a
      discussion about the necessity for the development of novel preclinical models of
      AD that better recapitulate human AD for the imaging to truly be meaningful and
      for substantive progress to be made toward understanding and effectively treating
      AD. Furthermore, the continued support of outstanding programs such as ADNI as
      well as the development of novel molecular imaging agents and MRI fast scanning
      sequences will also be requisite to effectively translate preclinical findings to
      the clinic.

PMID- 27033147
TI  - Novel minimal physiologically-based model for the prediction of passive tubular
      reabsorption and renal excretion clearance.
AB  - PURPOSE: Develop a minimal mechanistic model based on in vitro-in vivo
      extrapolation (IVIVE) principles to predict extent of passive tubular
      reabsorption. Assess the ability of the model developed to predict extent of
      passive tubular reabsorption (Freab) and renal excretion clearance (CLR) from in
      vitro permeability data and tubular physiological parameters. METHODS: Model
      system parameters were informed by physiological data collated following
      extensive literature analysis. A database of clinical CLR was collated for 157
      drugs. A subset of 45 drugs was selected for model validation; for those, Caco-2
      permeability (Papp) data were measured under pH6.5-7.4 gradient conditions and
      used to predict Freab and subsequently CLR. An empirical calibration approach was
      proposed to account for the effect of inter-assay/laboratory variation in Papp on
      the IVIVE of Freab. RESULTS: The 5-compartmental model accounted for regional
      differences in tubular surface area and flow rates and successfully predicted the
      extent of tubular reabsorption of 45 drugs for which filtration and reabsorption
      were contributing to renal excretion. Subsequently, predicted CLR was within 3
      fold of the observed values for 87% of drugs in this dataset, with an overall
      gmfe of 1.96. Consideration of the empirical calibration method improved overall
      prediction of CLR (gmfe=1.73 for 34 drugs in the internal validation dataset), in
      particular for basic drugs and drugs with low extent of tubular reabsorption.
      CONCLUSIONS: The novel 5-compartment model represents an important addition to
      the IVIVE toolbox for physiologically-based prediction of renal tubular
      reabsorption and CLR. Physiological basis of the model proposed allows its
      application in future mechanistic kidney models in preclinical species and human.

PMID- 27033148
TI  - Red blood cell coagulation induced by low-temperature plasma treatment.
AB  - Low-temperature plasma (LTP) treatment promotes blood clot formation by
      stimulation of the both platelet aggregation and coagulation factors. However,
      the appearance of a membrane-like structure in clots after the treatment is
      controversial. Based on our previous report that demonstrated characteristics of
      the form of coagulation of serum proteins induced by LTP treatment, we sought to
      determine whether treatment with two plasma instruments, namely BPC-HP1 and PN
      110/120TPG, formed clots only from red blood cells (RBCs). LTP treatment with
      each device formed clots from whole blood, whereas LTP treatment with BPC-HP1
      formed clots in phosphate-buffered saline (PBS) containing 2 * 10(9)/mL RBCs.
      Light microscopic analysis results showed that hemolysis formed clots consisting
      of materials with membrane-like structures from both whole blood and PBS
      suspended RBCs. Moreover, electron microscopic analysis results showed a
      monotonous material with high electron density in the formed clots, presenting a
      membrane-like structure. Hemolysis disappeared with the decrease in the current
      through the targets contacting with the plasma flare and clot formation ceased.
      Taken together, our results and those of earlier studies present two types of
      blood clot formation, namely presence or absence of hemolysis capability
      depending on the current through the targets.

PMID- 27033149
TI  - Oral health-related quality of life and implant therapy: A prospective
      multicenter study of preoperative, intermediate, and posttreatment assessment.
AB  - PURPOSE: Loss of teeth is associated with a significant reduction in quality of
      life. The aim of this prospective multicenter study was to assess the impact of
      dental implants on oral health-related quality of life (OHRQoL). MATERIAL AND
      METHODS: Patients with various kinds of indications for dental implants ranging
      from single-tooth loss to edentulous jaws were included. Quality of life related
      to dental implants was assessed through the Oral Health Impact Profile (OHIP-G
      21), which has a score from 0 to 20 in healthy patients. RESULTS: In total, 8689
      patients from 17 centers from 2009 to 2014 were enrolled in the study. The sex
      distribution was almost even (53.3% men, 46.7% women). The most frequent
      indications for the insertion of dental implants were free-end gaps (30.6%) and
      posterior single-tooth gaps (27%). In all, 12.4% of patients had an edentulous
      jaw. For all indications, patients reported significant changes in mean OHIP
      scores after prosthetic reconstruction. The most significant improvements in the
      OHIP score occurred in the groups of patients with edentulous jaws (pretreatment
      score: 42.3) after prosthodontic reconstruction (score: 24.8) and in the patient
      group with an anterior single-tooth gap (pretreatment score: 36.4) after
      prosthodontic reconstruction (score: 24.8). CONCLUSION: The insertion of dental
      implants and prosthodontic rehabilitation led to an improved OHRQoL for patients
      with all indications for dental implants, with the most significant improvements
      in patients with edentulous jaws and anterior single-tooth gaps.

PMID- 27033150
TI  - Growth Retardation, Loss of Desmosomal Adhesion, and Impaired Tight Junction
      Function Identify a Unique Role of Plakophilin 1 In Vivo.
AB  - Desmosomes mediate strong intercellular adhesion through desmosomal cadherins
      that interact with intracellular linker proteins including plakophilins (PKPs) 1
      3 to anchor the intermediate filaments. PKPs show overlapping but distinct
      expression patterns in the epidermis. So far, the contribution of individual PKPs
      in differentially regulating desmosome function is incompletely understood. To
      resolve the role of PKP1 we ablated the PKP1 gene. Here, we report that PKP1(-/-)
      mice were born at the expected mendelian ratio with reduced birth weight, but
      they otherwise appeared normal immediately after birth. However, their condition
      rapidly declined, and the mice died within 24 hours, developing fragile skin with
      lesions in the absence of obvious mechanical trauma. This was accompanied by
      sparse and small desmosomes. Newborn PKP1(-/-) mice showed disturbed tight
      junctions with an impaired inside-out barrier, whereas the outside-in barrier was
      unaffected. Keratinocytes isolated from these mice showed strongly reduced
      intercellular cohesion, delayed tight junction formation, and reduced
      transepithelial resistance and reduced proliferation rates. Our study shows a
      nonredundant and essential role of PKP1 in desmosome and tight junction function
      and supports a role of PKP1 in growth control, a function that is crucial in
      wound healing and epidermal carcinogenesis.

PMID- 27033151
TI  - The effects of co-medications on lamotrigine clearance in Japanese children with
      epilepsy.
AB  - PURPOSE: Although it has been reported that some antiepileptic drugs have
      inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have
      the same effects in Asian epilepsy patients as in those in other countries has
      not been clarified, especially in children. The aim of this study was to
      determine the effects of co-medications on LTG clearance in Japanese children
      with epilepsy. METHODS: A total of 342 routine serum concentration measurements
      of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The
      dose-corrected concentration (DCC) of LTG was calculated as
      [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co
      medication. The difference in the DCC of LTG was compared between patients with
      and without valproic acid (VPA) and between those with and without drugs inducing
      glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and
      phenobarbital (PB)). RESULTS: The DCC of LTG was significantly higher in patients
      on VPA and significantly lower in patients on drugs inducing glucuronic acid
      conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly
      higher in patients on CBZ than in patients on PHT or PB. There was no correlation
      between the DCC of LTG and the concentration of VPA or metabolic inducers within
      the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam,
      zonisamide, and levetiracetam had little effect on LTG concentration. CONCLUSION:
      LTG concentration changes dramatically with concomitant antiepileptic drugs in
      Japanese children, as previously reported from other countries, and special
      attention is required. Although the dose of LTG should be adjusted when starting
      or discontinuing VPA or metabolic inducers, no adjustment is needed when changing
      the dose of VPA or metabolic inducers in the therapeutic range.

PMID- 27033152
TI  - Lipids in pollen - They are different.
AB  - During evolution, the male gametophyte of Angiosperms has been severely reduced
      to the pollen grain, consisting of a vegetative cell containing two sperm cells.
      This vegetative cell has to deliver the sperm cells from the stigma through the
      style to the ovule. It does so by producing a pollen tube and elongating it to
      many centimeters in length in some species, requiring vast amounts of fatty acid
      and membrane lipid synthesis. In order to optimize this polar tip growth, a
      unique lipid composition in the pollen has evolved. Pollen tubes produce
      extraplastidial galactolipids and store triacylglycerols in lipid droplets,
      probably needed as precursors of glycerolipids or for acyl editing. They also
      possess special sterol and sphingolipid moieties that might together form
      microdomains in the membranes. The individual lipid classes, the proteins
      involved in their synthesis as well as the corresponding Arabidopsis knockout
      mutant phenotypes are discussed in this review. This article is part of a Special
      Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. 

PMID- 27033154
TI  - A partly-contacted epitaxial lateral overgrowth method applied to GaN material.
AB  - We have discussed a new crystal epitaxial lateral overgrowth (ELO) method, partly
      contacted ELO (PC-ELO) method, of which the overgrowth layer partly-contacts with
      underlying seed layer. The passage also illustrates special mask structures with
      and without lithography and provides three essential conditions to achieve the PC
      ELO method. What is remarkable in PC-ELO method is that the tilt angle of
      overgrowth stripes could be eliminated by contacting with seed layer. Moreover,
      we report an improved monolayer microsphere mask method without lithography of PC
      ELO method, which was used to grow GaN. From the results of scanning electron
      microscopy, cathodoluminescence, x-ray diffraction (XRD), transmission electron
      microscopy, and atomic force microscope (AFM), overgrowth layer shows no tilt
      angle relative to the seed layer and high quality coalescence front (with average
      linear dislocation density <6.4 * 10(3) cm(-1)). Wing stripes peak splitting of
      the XRD rocking curve due to tilt is no longer detectable. After coalescence,
      surface steps of AFM show rare discontinuities due to the low misorientation of
      the overgrowth regions. 

PMID- 27033153
TI  - Serotonin modulates glutamatergic transmission to neurons in the lateral
      habenula.
AB  - The lateral habenula (LHb) is bilaterally connected with serotoninergic raphe
      nuclei, and expresses high density of serotonin receptors. However, actions of
      serotonin on the excitatory synaptic transmission to LHb neurons have not been
      thoroughly investigated. The LHb contains two anatomically and functionally
      distinct regions: lateral (LHbl) and medial (LHbm) divisions. We compared
      serotonin's effects on glutamatergic transmission across the LHb in rat brains.
      Serotonin bi-directionally and differentially modulated glutamatergic
      transmission. Serotonin inhibited glutamatergic transmission in higher percentage
      of LHbl neurons but potentiated in higher percentage of LHbm neurons. Magnitude
      of potentiation was greater in LHbm than in LHbl. Type 2 and 3 serotonin receptor
      antagonists attenuated serotonin's potentiation. The serotonin reuptake blocker,
      and the type 2 and 3 receptor agonists facilitated glutamatergic transmission in
      both LHbl and LHbm neurons. Thus, serotonin via activating its type 2, 3
      receptors, increased glutamate release at nerve terminals in some LHb neurons.
      Our data demonstrated that serotonin affects both LHbm and LHbl. Serotonin might
      play an important role in processing information between the LHb and its
      downstream-targeted structures during decision-making. It may also contribute to
      a homeostatic balance underlying the neural circuitry between the LHb and raphe
      nuclei. 

PMID- 27033155
TI  - Association Between Symptom Burden and Time to Hospitalization, Nursing Home
      Placement, and Death Among the Chronically Ill Urban Homebound.
AB  - CONTEXT: Homebound adults experience significant symptom burden. OBJECTIVES: To
      examine demographic and clinical characteristics associated with high symptom
      burden in the homebound, and to examine associations between symptom burden and
      time to hospitalization, nursing home placement, and death. METHODS: Three
      hundred eighteen patients newly enrolled in the Mount Sinai Visiting Doctors
      Program, an urban home-based primary care program, were studied. Patient
      sociodemographic characteristics, symptom burden (measured via the Edmonton
      Symptom Assessment Scale), and incidents of hospitalization, nursing home
      placement, and death were collected via medical chart review. Multivariate Cox
      proportional hazards models were used to analyze the effect of high symptom
      burden on time to first hospitalization, nursing home placement, and death.
      RESULTS: Of the study sample, 45% had severe symptom burden (i.e., Edmonton
      Symptom Assessment Scale score >6 on at least one symptom). Patients with severe
      symptom burden were younger (82.0 vs. 85.5 years, P < 0.01), had more comorbid
      conditions (3.2 vs. 2.5 Charlson score, P < 0.01), higher prevalence of
      depression (43.4% vs. 12.0%, P < 0.01), lower prevalence of dementia (34.3% vs.
      60.6%, P < 0.01), and used fewer hours of home health services (73.6 vs. 94.4
      hours/wk, P < 0.01). Severe symptom burden was associated with a shorter time to
      first hospitalization (hazard ratio = 1.51, 95% CI 1.06-2.15) in adjusted models
      but had no association with time to nursing home placement or death. CONCLUSION:
      The homebound with severe symptom burden represents a unique cohort of patients
      who are at increased risk of hospitalization. Tailored symptom management via
      home-based primary and palliative care programs may prevent unnecessary health
      care utilization in this population.

PMID- 27033156
TI  - Novel Data Sharing Between a Comprehensive Cancer Center and a Private Payer to
      Better Understand Care at the End of Life.
AB  - CONTEXT: Understanding end-of-life (EOL) care patterns is a prerequisite to
      improving the experience for cancer patients. EOL measures endorsed by the
      National Quality Forum (NQF) have been examined in older patients using Medicare
      claims. OBJECTIVES: To evaluate EOL care for patients treated at a comprehensive
      cancer center, using private payer claims data. METHODS: A retrospective cohort
      study was conducted of Dana-Farber Cancer Institute (DFCI) patients who died
      between July 2010 and December 2012, and were insured by Blue Cross Blue Shield
      of Massachusetts. Primary data sources included Blue Cross Blue Shield of
      Massachusetts claims information and DFCI administrative data. We assessed NQF
      endorsed measures of EOL care related to emergency department visits,
      hospitalizations, and intensive care unit admissions in the last 30 days,
      chemotherapy in the last 14 days, hospice stay, and death in an acute care
      setting. Patterns of care by cancer type and service location were determined.
      RESULTS: Among 674 patients (mean age 58 years), event rates for NQF-endorsed EOL
      measures were similar to those reported using Medicare claims. Decedents with
      hematologic malignancies received significantly more intensive care and were less
      likely to have enrolled in hospice, compared to decedents with solid tumors.
      Thirty to 45% of EOL events occurred outside of DFCI and its affiliated
      hospitals. CONCLUSION: Data sharing between a private payer and a large cancer
      center proved feasible and informative. High rates of hospital service use
      outside of our sites of care were unexpected. The findings suggest opportunities
      to better manage care at the end of life.

PMID- 27033157
TI  - Re: The Influence of Low Salivary Flow Rates on Sublingual Fentanyl Absorption
      for Breakthrough Cancer Pain.

PMID- 27033158
TI  - Immigrants Accessing End-of-Life Care in Italy: The Tuscany Tumor Association
      Experience.

PMID- 27033159
TI  - High Symptom Burden Among Patients With Newly Diagnosed Incurable Cancer in a
      Developing Country.

PMID- 27033160
TI  - Reply to Meijler.

PMID- 27033161
TI  - Peer Mentorship Programs for Breast Cancer Patients.

PMID- 27033162
TI  - Occupational Dose and Dose Limits: Experience in a Large Multisite Hospital
      System.
AB  - PURPOSE: The Nuclear Regulatory Commission (NRC) has recently proposed changes
      that reduce the occupational dose limits for lens dose equivalent (LDE),
      embryo/fetus dose, and administrative control levels (ACLs) related to deep dose
      equivalent (DDE). This study collected occupational dose data from a large
      hospital system and determined how proposed NRC regulatory changes may affect
      worker and hospital workflow. METHODS: Radiation badge data were collected for
      1,305 workers, from between 2013 and 2014, and 180 pregnancies, from between 2009
      and 2014. Median values for LDE, DDE, and embryo/fetus dose were determined.
      Current and proposed NRC regulations were applied, and the percentage of workers
      exceeding regulatory limits/ACLs was recorded. Fisher's exact test was applied to
      determine if physicians were disproportionately affected by dose regulations.
      RESULTS: Median doses were one to two orders of magnitude lower than current
      annual dose limits prescribed by the NRC. Proposed NRC regulations significantly
      increased the percentage of workers who exceeded limits and ACLs. Interventional
      radiologists, pain medicine physicians, and cardiologists working in catheter
      laboratories were most affected by LDE limits and DDE ACLs. Nuclear medicine
      technologists were most affected by embryo/fetus limits. Physicians were
      disproportionately affected by regulations (odds ratio 26.86; P < .0001).
      CONCLUSIONS: Proposed NRC regulatory changes will cause a small increase in the
      number of workers who exceed ACLs and limits. Physicians and pregnant nuclear
      medicine workers are most affected and may need to alter their workloads.
      Practical difficulties in implementing cumulative dose tracking, and use of an
      LDE shielding factor, should be considered.

PMID- 27033163
TI  - Transient potential receptor melastatin-2 (Trpm2) does not influence murine MLL
      AF9-driven AML leukemogenesis or in vitro response to chemotherapy.
AB  - Transient potential receptor melastatin-2 (TRPM2) is a nonselective cationic,
      Ca(2+)-permeable transmembrane pore that is preferentially expressed in cells of
      the myeloid lineage and modulates signaling pathways converging into NF-kB. This
      is of potential interest for acute myeloid leukemia (AML) therapy, as NF-kappaB
      signaling is emerging as a key pathway, mediating drug resistance and leukemia
      initiating cell survival in AML. Inhibition of NF-kappaB signaling has been found
      to be synergistic with chemotherapy. TRPM2 is overexpressed in AML compared with
      normal bone marrow, with the highest levels in the FAB M3-6 subtypes. To
      determine the effect of TRPM2 depletions in a defined genetic model, we
      established MLL-AF9-driven AML on a Trpm2(-/-) genetic background. Trpm2(-/-) MLL
      AF9 leukemias displayed reduced NF-kappaB phosphorylation as well as nuclear
      translocation. In vivo, primary and secondary recipients of Trpm2(-/-) MLL-AF9
      leukemias exhibit increased latency compared with recipients of wild-type
      leukemia cells. However, the difference in latency was small and was lost in
      tertiary transplants. The effect of loss of Trpm2 in a BCR-ABL/NUP98-HOXA9 fusion
      model was even smaller. Given reports that loss or inhibition of TRPM2 enhanced
      killing by DNA-damaging agents in neuroblastoma, breast cancer, and prostate
      cancer cell lines, we exposed Trpm2(-/-) and Trpm2(wt) primary MLL-AF9 leukemias
      to doxorubicin, cytarabine, and etoposide, but found no difference in IC50
      values. The in vitro response to decitabine was also unaffected. In summary,
      Trpm2 does not seem to play a major role in myeloid leukemogenesis. Additionally,
      loss of Trpm2 does not augment the cytotoxicity of standard AML chemotherapeutic
      agents.

PMID- 27033164
TI  - Essential role of Ufm1 conjugation in the hematopoietic system.
AB  - Protein modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins plays a
      pivotal role in a wide range of cellular functions and signaling pathways. The
      Ufm1 conjugation system is a novel ubiquitin-like system that consists of Ufm1,
      Uba5 (E1), Ufc1 (E2), and less defined E3 ligase(s) and targets. Despite its
      discovery more than a decade ago, its biological functions and working mechanism
      remains poorly understood. Recent genetic studies using knockout mouse models
      provide unambiguous evidence for the indispensable role of the Ufm1 system in
      animal development and hematopoiesis, especially erythroid development. In this
      short review, we summarize the recent progress on this important protein
      modification system and highlight potential challenges ahead. Further elucidation
      of the function and working mechanism of the ufmylation pathway would provide
      insight into disease pathogenesis and novel therapeutic targets for blood-related
      diseases such as anemia.

PMID- 27033165
TI  - Improving the Sensitivity, Resolution, and Peak Capacity of Gradient Elution in
      Capillary Liquid Chromatography with Large-Volume Injections by Using Temperature
      Assisted On-Column Solute Focusing.
AB  - Capillary HPLC (cLC) with gradient elution is the separation method of choice for
      the fields of proteomics and metabolomics. This is due to the complementary
      nature of cLC flow rates and electrospray or nanospray ionization mass
      spectrometry (ESI-MS). The small column diameters result in good mass
      sensitivity. Good concentration sensitivity is also possible by injection of
      relatively large volumes of solution and relying on solvent-based solute
      focusing. However, if the injection volume is too large or solutes are poorly
      retained during injection, volume overload occurs which leads to altered peak
      shapes, decreased sensitivity, and lower peak capacity. Solutes that elute early
      even with the use of a solvent gradient are especially vulnerable to this
      problem. In this paper, we describe a simple, automated instrumental method,
      temperature-assisted on-column solute focusing (TASF), that is capable of
      focusing large volume injections of small molecules and peptides under gradient
      conditions. By injecting a large sample volume while cooling a short segment of
      the column inlet at subambient temperatures, solutes are concentrated into narrow
      bands at the head of the column. Rapidly raising the temperature of this segment
      of the column leads to separations with less peak broadening in comparison to
      solvent focusing alone. For large volume injections of both mixtures of small
      molecules and a bovine serum albumin tryptic digest, TASF improved the peak shape
      and resolution in chromatograms. TASF showed the most dramatic improvements with
      shallow gradients, which is particularly useful for biological applications.
      Results demonstrate the ability of TASF with gradient elution to improve the
      sensitivity, resolution, and peak capacity of volume overloaded samples beyond
      gradient compression alone. Additionally, we have developed and validated a
      double extrapolation method for predicting retention factors at extremes of
      temperature and mobile phase composition. Using this method, the effects of TASF
      can be predicted, allowing determination of the usefulness of this technique for
      a particular application.

PMID- 27033166
TI  - Production possibility frontiers and socioecological tradeoffs for restoration of
      fire adapted forests.
AB  - We used spatial optimization to analyze alternative restoration scenarios and
      quantify tradeoffs for a large, multifaceted restoration program to restore
      resiliency to forest landscapes in the western US. We specifically examined
      tradeoffs between provisional ecosystem services, fire protection, and the
      amelioration of key ecological stressors. The results revealed that attainment of
      multiple restoration objectives was constrained due to the joint spatial patterns
      of ecological conditions and socioeconomic values. We also found that current
      restoration projects are substantially suboptimal, perhaps the result of
      compromises in the collaborative planning process used by federal planners, or
      operational constraints on forest management activities. The juxtaposition of
      ecological settings with human values generated sharp tradeoffs, especially with
      respect to community wildfire protection versus generating revenue to support
      restoration and fire protection activities. The analysis and methods can be
      leveraged by ongoing restoration programs in many ways including: 1) integrated
      prioritization of restoration activities at multiple scales on public and
      adjoining private lands, 2) identification and mapping of conflicts between
      ecological restoration and socioeconomic objectives, 3) measuring the efficiency
      of ongoing restoration projects compared to the optimal production possibility
      frontier, 4) consideration of fire transmission among public and private land
      parcels as a prioritization metric, and 5) finding socially optimal regions along
      the production frontier as part of collaborative restoration planning. 

PMID- 27033167
TI  - Enzyme replacement therapy with laronidase (Aldurazyme((r))) for treating
      mucopolysaccharidosis type I.
AB  - BACKGROUND: Mucopolysaccharidosis type I can be classified as three clinical sub
      types; Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome, with the
      scale of severity being such that Hurler syndrome is the most severe and Scheie
      syndrome the least severe. It is a rare, autosomal recessive disorder caused by a
      deficiency of alpha-L-iduronidase. Deficiency of this enzyme results in the
      accumulation of glycosaminoglycans within the tissues. The clinical
      manifestations are facial dysmorphism, hepatosplenomegaly, upper airway
      obstruction, skeletal deformity and cardiomyopathy. If Hurler syndrome is left
      untreated, death ensues by adolescence. There are more attenuated variants termed
      Hurler-Scheie or Scheie syndrome, with those affected potentially not presenting
      until adulthood. Enzyme replacement therapy has been used for a number of years
      in the treatment of Hurler syndrome, although the current gold standard would be
      a haemopoietic stem cell transplant in those diagnosed by 2.5 years of age. This
      is an updated version of the original Cochrane review published in 2013.
      OBJECTIVES: To evaluate the effectiveness and safety of treating
      mucopolysaccharidosis type I with laronidase enzyme replacement therapy as
      compared to placebo. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, MEDLINE
      via OVID and Embase.Date of most recent search: 05 October 2015. SELECTION
      CRITERIA: Randomised and quasi-randomised controlled studies of laronidase enzyme
      replacement therapy compared to placebo. DATA COLLECTION AND ANALYSIS: Two
      authors independently screened the identified studies. The authors then appraised
      and extracted data. MAIN RESULTS: One study of 45 patients met the inclusion
      criteria. This double-blind, placebo-controlled, randomised, multinational study
      looked at laronidase at a dose of 0.58 mg/kg/week versus placebo in patients with
      mucopolysaccharidosis type I. All primary outcomes listed in this review were
      studied in this study. The laronidase group achieved statistically significant
      improvements in per cent predicted forced vital capacity compared to placebo, MD
      5.60 (95% confidence intervals 1.24 to 9.96) and in the six-minute-walk test
      (mean improvement of 38.1 metres in the laronidase group; P = 0.039, when using a
      prospectively planned analysis of covariance). The levels of urinary
      glycoaminoglycans were also significantly reduced. In addition, there were
      improvements in hepatomegaly, sleep apnoea and hypopnoea. Laronidase antibodies
      were detected in nearly all patients in the treatment group with no apparent
      clinical effect and titres were reducing by the end of the study. Infusion
      related adverse reactions occurred in both groups but all were mild and none
      necessitated medical intervention or infusion cessation. AUTHORS' CONCLUSIONS:
      The current evidence demonstrates that laronidase is effective when compared to
      placebo in the treatment of mucopolysaccharidosis type I. The included study was
      comprehensive and of good quality, although there were few participants. The
      study included all of the key outcome measures we wished to look at. It
      demonstrated that laronidase is efficacious in relation to reducing biochemical
      parameters (reduced urine glycosaminoglycan excretion) and improved functional
      capacity as assessed by forced vital capacity and the six-minute-walk test. In
      addition glycosaminoglycan storage was reduced as ascertained by a reduction in
      liver volume. Laronidase appeared to be safe and, while antibodies were
      generated, these titres were reducing by the end of the study. More studies are
      required to determine long-term effectiveness and safety and to assess the impact
      upon quality of life. Enzyme replacement therapy with laronidase can be used pre-
      and peri-haemopoietic stem cell transplant, which is now the gold standard
      treatment in those patients diagnosed under 2.5 years of age.

PMID- 27033168
TI  - Host genetics is associated with the gut microbial community membership rather
      than the structure.
AB  - The issue of what factors shape the gut microbiota has been studied for years.
      However, questions on the contribution of host genetics to the colonizing process
      of the gut microbiota and to the extent that host genetics affect the gut
      microbiota have not yet been clearly answered. Most recently published reports
      have concluded that host genetics make a smaller contribution than other factors,
      such as diet, in determining the gut microbiota. Here we have exploited the
      increasing amount of fecal 16S rRNA gene sequencing data that are becoming
      available to conduct an analysis to assess the influence of host genetics on the
      diversity of the gut microbiota. By re-analyzing data obtained from over 5000
      stool samples, representing individuals living on five continents and ranging in
      age from 3 days to 87 years, we found that the strength of the various factors
      affecting the membership or structure of the gut microbiota are quite different,
      which leads us to a hypothesis that the presence or absence of taxa is largely
      controlled by host genetics, whereas non-genetic factors regulate the abundance
      of each taxon. This hypothesis is supported by the finding that the genome
      similarity positively correlates with the similarity of community membership.
      Finally, we showed that only severe perturbations are able to alter the gut
      microbial community membership. In summary, our work provides new insights into
      understanding the complexities of the gut microbial community and how it responds
      to changes imposed on it.

PMID- 27033169
TI  - Chemical composition and antimicrobial activity of the essential oils of
      Onychopetalum amazonicum R.E.Fr.
AB  - The essential oils from leaves, twigs and trunk bark of Onychopetalum amazonicum
      R.E. Fr. (Annonaceae), obtained by hydrodistillation, were analysed by GC and GC
      MS, and also were evaluated for in vitro antimicrobial activity. Forty-one
      compounds, which correspond to 75.0-92.2% of the oil components, were identified.
      Major compounds were sesquiterpenes, including (E)-caryophyllene, caryophyllene
      oxide, spathulenol, alpha-gurjunene, allo-aromadendrene and alpha-epi-cadinol.
      The oils were evaluated for antimicrobial activities against four bacteria
      strains and five pathogenic fungi. The oil of the trunk bark exhibited good
      activity against Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC
      10538 and Kocuria rhizophila ATCC 9341, with a minimal inhibitory concentration
      of 62.5 MUg/mL. The essential oil composition and the antimicrobial evaluation
      are reported for the first time for the genus Onychopetalum. 

PMID- 27033171
TI  - Retraction notice to "S14G-humanin Ameliorates Abeta 25-35-induced Behavioral
      Deficits by Reducing Neuroinflammatory Responses and Apoptosis in Mice"
      [Neuropeptides 42/5-6 (2008) 557-567].

PMID- 27033170
TI  - Repeated FcepsilonRI triggering reveals modified mast cell function related to
      chronic allergic responses in tissue.
AB  - BACKGROUND: Activation of mast cells through FcepsilonRI plays an important role
      in acute allergic reactions. However, little is known about the function of mast
      cells in patients with chronic allergic inflammation or the effect of repeated
      FcepsilonRI triggering occurring in such responses. OBJECTIVE: We aimed to
      identify changes in mast cell function after repeated FcepsilonRI triggering and
      to correlate these changes to chronic allergic responses in tissue. METHODS:
      Human cord blood-derived mast cells were treated for 2 weeks with anti-IgE. The
      function of naive or treated mast cells was analyzed by means of RNA sequencing,
      quantitative RT-PCR, flow cytometry, and functional assays. Protein secretion was
      measured with ELISAs and multiplex assays. RESULTS: We observed several changes
      in mast cell function after repeated anti-IgE triggering. Although the acute
      response was dampened, we identified 289 genes significantly upregulated after
      repeated anti-IgE. Most of these genes (84%) were not upregulated after a single
      anti-IgE stimulus, indicating a significantly different response mode
      characterized by increased antigen presentation, response to bacteria, and
      chemotaxis. Changes in mast cell function were related to changes in expression
      of the transcription factors RXRA and BATF and others. Importantly, we found a
      substantial overlap between genes upregulated after repeated anti-IgE triggering
      and genes upregulated in tissue from patients with chronic allergy, in particular
      those of patients with chronic rhinosinusitis. CONCLUSION: Our study provides
      evidence for intrinsic modulation of mast cell function on repeated FcepsilonRI
      mediated activation. The overlap with gene expression in tissues is suggestive of
      a direct link between repeated IgE-mediated activation of mast cells and chronic
      allergy.

PMID- 27033173
TI  - IFN-beta differentially regulates the function of T cell subsets in MS and EAE.
AB  - Multiple sclerosis (MS) is considered as a T cell mediated autoimmune disease of
      the CNS, although a pathogenic role has also been attributed to other immune cell
      types as well as to environmental and genetic factors. Considering that T cells
      are interesting from an immunopathogenic point of view and consequently from a
      therapeutic perspective, various T cell targeted therapies have been approved for
      MS. Interferon beta (IFN-beta) is widely used as first-line intervention for
      modulating T cell responses, although its pleiotropic and multifaceted activities
      influence its effectiveness on the disease development, with mechanisms that are
      not yet fully understood. Since different T cell populations, including pro
      inflammatory and regulatory T cells, might affect the course of MS, the effects
      of IFN-beta become even more complex. This review will summarize recent findings
      regarding the T cell targeted effect of IFN-beta in MS and its animal model EAE,
      with emphasis on the direct actions of endogenous and exogenous IFN-beta on each
      T cell subpopulation involved in CNS autoimmunity. Delineating how IFN-beta
      exerts its action on different T cell types may eventually contribute to the
      designing of therapeutic strategies aiming to improve the effectiveness of this
      drug for MS treatment.

PMID- 27033172
TI  - Dyslipidemia and its risk factors among urban middle-aged Iranians: A population
      based study.
AB  - AIMS: Dyslipidemia is a known risk factor for cardiovascular disease and is a
      leading cause of mortality in developed and developing countries. This study was
      aimed to determine the prevalence of dyslipidemia and its risk factors in an
      urban group of Iranian adult population. METHODS: In this study, based on the
      criteria set by the National Cholesterol Education Program, the prevalence of
      dyslipidemia was evaluated in a population of 4737 people aged 45-69 years who
      participated in the second phase of an ophthalmology cohort study in Shahroud.
      Dyslipidemia prevalence was determined by age, sex, and risk factors of the
      disease; the findings were tested by using simple and multiple logistic
      regression. RESULTS: The prevalence of dyslipidemia was 66.5% (CI 95%: 64.4-68.6)
      in males, 61.3% (CI 95%: 59.5-63.2) in females, and 63.4% (CI 95%: 62.0-64.9%) in
      both sexes. The prevalence of hypertriglyceridemia, hypercholesterolemia, low HDL
      C, and high LDL-C, respectively, was 28.8%, 13.4%, 42.3%, and 13.4%,
      respectively. In multivariate logistic regression model, increase of age (for
      females), abdominal obesity, overweight and obesity, hypertension, and diabetes
      were associated with an increased odd of dyslipidemia. CONCLUSION: The prevalence
      of dyslipidemia in middle-aged urban population in Iran is high, and with
      increasing age there is an increased risk of dyslipidemia. Hence, considering the
      growing trend of aging in Iran, there is need for taking special measures to deal
      with dyslipidemia as a health priority. Furthermore, the need for planning in
      order to reduce the risk of dyslipidemia and prevent its complications is greater
      than ever.

PMID- 27033174
TI  - The IL-17A/IL-17RA axis in pulmonary defence and immunopathology.
AB  - The interleukin (IL)-17A/IL-17 receptor A (IL-17RA) axis is emerging as a key
      player in host defence. Several studies have demonstrated that IL-17A-mediated
      responses play a critical role in both acute and chronic inflammation induced by
      infectious agents, environmental stimuli and genetic diseases in the airways. In
      this regard, it is becoming evident that IL-17A/IL-17RA signalling may have a
      protective and beneficial impact on health, but that it can also result in
      detrimental outcomes. On one hand, the IL-17A/IL-17RA axis can contribute to the
      elimination of noxious stimuli and to the resolution of acute inflammatory
      processes; on the other hand, it can exacerbate immunopathological responses,
      contributing to the development and progression of chronic respiratory illnesses.
      In addition, cellular and molecular signatures underlying IL-17A/IL-17RA
      signalling have been increasingly identified, although further studies are needed
      to clarify such complex responses. Here, we discuss the latest discoveries on the
      role of the IL-17A/IL-17RA axis in driving host pulmonary defence and
      immunopathology.

PMID- 27033175
TI  - Information system end-user satisfaction and continuance intention: A unified
      modeling approach.
AB  - CONTEXT: Permanent evaluation of end-user satisfaction and continuance intention
      is a critical issue at each phase of a clinical information system (CIS) project,
      but most validation studies are concerned with the pre- or early post-adoption
      phases. OBJECTIVE: The purpose of this study was twofold: to validate at the
      Pompidou University Hospital (HEGP) an information technology late post-adoption
      model built from four validated models and to propose a unified metamodel of
      evaluation that could be adapted to each context or deployment phase of a CIS
      project. METHODS: Five dimensions, i.e., CIS quality (CISQ), perceived usefulness
      (PU), confirmation of expectations (CE), user satisfaction (SAT), and continuance
      intention (CI) were selected to constitute the CI evaluation model. The validity
      of the model was tested using the combined answers to four surveys performed
      between 2011 and 2015, i.e., more than ten years after the opening of HEGP in
      July 2000. Structural equation modeling was used to test the eight model
      associated hypotheses. RESULTS: The multi-professional study group of 571
      responders consisted of 158 doctors, 282 nurses, and 131 secretaries. The
      evaluation model accounted for 84% of variance of satisfaction and 53% of CI
      variance for the period 2011-2015 and for 92% and 69% for the period 2014-2015.
      In very late post adoption, CISQ appears to be the major determinant of
      satisfaction and CI. Combining the results obtained at various phases of CIS
      deployment, a Unified Model of Information System Continuance (UMISC) is
      proposed. CONCLUSION: In a meaningful CIS use situation at HEGP, this study
      confirms the importance of CISQ in explaining satisfaction and CI. The proposed
      UMISC model that can be adapted to each phase of CIS deployment could facilitate
      the necessary efforts of permanent CIS acceptance and continuance evaluation.

PMID- 27033176
TI  - Hashimoto Encephalopathy Presenting With Stroke-Like Episodes in an Adolescent
      Female: A Case Report and Literature Review.
AB  - BACKGROUND: Hashimoto encephalopathy is a rare form of encephalopathy thought to
      be of autoimmune etiology. Cognitive changes and seizures are the most commonly
      reported presenting manifestation. Stroke-like episodes have also been documented
      in these individuals. We describe a rare adolescent with Hashimoto encephalopathy
      who presented with stroke-like symptoms. PATIENT DESCRIPTION: A previously well
      15-year-old girl experienced sudden-onset language disturbance and right
      hemiparesis. Her symptoms resolved, but weeks later, she began experiencing
      refractory seizures, episodes of status epilepticus, and cognitive decline. An
      extensive evaluation was unremarkable, but thyroid peroxidase antibodies were
      elevated, and a diagnosis of Hashimoto encephalitis was made. Steroid therapy was
      initiated, and her symptoms resolved with return to baseline cognitive function.
      CONCLUSION: Hashimoto encephalopathy is a highly treatable condition that may be
      considered in the differential diagnosis of children and adolescents presenting
      with stroke-like symptoms.

PMID- 27033177
TI  - Applications of PLOR in labeling large RNAs at specific sites.
AB  - Incorporation of modified or labeled nucleotides at specific sites in RNAs is
      critical for gaining insights into the structure and function of RNAs.
      Preparation of site-specifically labeled large RNAs in amounts suitable for
      structural or functional studies is extremely difficult using current
      methodologies. The position-selective labeling of RNA, PLOR, is a recently
      developed method that makes such syntheses possible. PLOR allows incorporation of
      various probes, including (2)D/(13)C/(15)N-isotopic labels,
      Cy3/Cy5/Alexa488/Alexa555 fluorescent dyes, biotin and other chemical groups,
      into specific positions in long RNAs. Here, we describe in detail the use of PLOR
      to label RNAs at specific segment(s) or discrete sites.

PMID- 27033179
TI  - Treatment of experimental furcation perforations with mineral trioxide aggregate,
      platelet rich plasma or platelet rich fibrin in dogs' teeth.
AB  - This work evaluates the effect of mineral trioxide aggregate (MTA), platelet rich
      plasma (PRP) or platelet rich fibrin (PRF) on healing of non-contaminated and
      contaminated furcation perforations. A total of 192 teeth of 12 dogs was divided
      into three equal groups according to evaluation period. Each group was further
      subdivided into MTA, PRP, PRF, negative and positive control subgroups. Each
      experimental subgroup was further subdivided according to perforation status into
      non-contaminated and contaminated subdivisions. Root canal therapy was carried
      out and furcation perforation was made in all teeth except in negative control
      subgroup. The furcation perforation was repaired immediately in subdivision (1)
      and after 4 weeks in subdivision (2). The change in vertical bone loss was
      measured by radiography. Inflammatory cell count, cemental deposition, new bone
      formation, bone resorption and epithelial proliferation were assessed. Both PRP
      and PRF demonstrated statistically significant reduction in vertical bone loss
      and inflammatory cell count than MTA. No significant difference was found between
      MTA, PRP and PRF in cemental deposition, new bone formation, bone resorption and
      epithelial proliferation. The non-contaminated teeth demonstrated better
      treatment outcomes than the contaminated teeth. In conclusion, PRP and PRF are
      successful treatment options for repairing of furcation perforation in both non
      contaminated and contaminated teeth in dogs with superior outcomes in non
      contaminated teeth. 

PMID- 27033178
TI  - Sequence mapping of transfer RNA chemical modifications by liquid chromatography
      tandem mass spectrometry.
AB  - Mass spectrometry is a powerful analytical tool for identifying and
      characterizing structural modifications to the four canonical bases in RNA,
      information that is lost when using techniques such as PCR for RNA analysis. Here
      we described an updated method for sequence mapping of modified nucleosides in
      transfer RNA. This modification mapping approach utilizes knowledge of the
      modified nucleosides present in the sample along with the genome-derived tRNA
      sequence to readily locate modifications site-specifically in the tRNA sequence.
      The experimental approach involves isolation of the tRNA of interest followed by
      separate enzymatic digestion to nucleosides and oligonucleotides. Both samples
      are analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and the
      data sets are then combined to yield the modification profile of the tRNA. Data
      analysis is facilitated by the use of unmodified sequence exclusion lists and new
      developments in software that can automate MS/MS spectral annotation. The method
      is illustrated using tRNA-Asn isolated from Thermus thermophilus.

PMID- 27033182
TI  - Optimizing a custom tiling microarray for low input detection and identification
      of unamplified virus targets.
AB  - Viruses are major pathogens causing foodborne illnesses and are often present at
      low levels in foods, thus requiring sensitive techniques for their detection in
      contaminated foods. The lack of efficient culture methods for many foodborne
      viruses and the potential for multi-species viral contamination have driven
      investigation toward non-amplification based methods for virus detection and
      identification. A custom DNA microarray (FDA_EVIR) was assessed for its
      sensitivity in the detection and identification of low-input virus targets, human
      hepatitis A virus, norovirus, and coxsackievirus, individually and in
      combination. Modifications to sample processing were made to accommodate low
      input levels of unamplified virus targets, which included addition of carrier
      cDNA, RNase treatment, and optimization of DNase I-mediated target fragmentation.
      Amplification-free detection and identification of foodborne viruses were
      achieved in the range of 250-500 copies of virus RNA. Alternative data analysis
      methods were employed to distinguish the genotypes of the viruses particularly at
      lower levels of target input and the single probe-based analysis approach made it
      possible to identify a minority species in a multi-virus complex. The
      oligonucleotide array is shown to be a promising platform to detect foodborne
      viruses at low levels close to what are anticipated in food or environmental
      samples.

PMID- 27033181
TI  - Click labeling of unnatural sugars metabolically incorporated into viral envelope
      glycoproteins enables visualization of single particle fusion.
AB  - Enveloped viruses infect target cells by fusing their membrane with cellular
      membrane through a process that is mediated by specialized viral glycoproteins.
      The inefficient and highly asynchronous nature of viral fusion complicates
      studies of virus entry on a population level. Single virus imaging in living
      cells has become an important tool for delineating the entry pathways and for
      mechanistic studies of viral fusion. We have previously demonstrated that
      incorporation of fluorescent labels into the viral membrane and trapping
      fluorescent proteins in the virus interior enables the visualization of single
      virus fusion in living cells. Here, we implement a new approach to non-invasively
      label the viral membrane glycoproteins through metabolic incorporation of
      unnatural sugars followed by click-reaction with organic fluorescent dyes. This
      approach allows for efficient labeling of diverse viral fusion glycoproteins on
      the surface of HIV pseudoviruses. Incorporation of a content marker into surface
      labeled viral particles enables sensitive detection of single virus fusion with
      live cells. 

PMID- 27033180
TI  - Assessment of a carbon fibre MRI flatbed insert for radiotherapy treatment
      planning.
AB  - OBJECTIVE: The purpose of this work was to assess heating and radiofrequency (RF)
      deposition and image quality effects of a prototype three-section carbon fibre
      flatbed insert for use in MRI. METHODS: RF deposition was assessed using two
      different thermometry techniques, infrared thermometry and Bragg-grating
      thermometry. Image quality effects were assessed with and without the flatbed
      insert in place by using mineral oil phantoms and a human subject. RESULTS:
      Neither technique detected heating of the insert in typical MRI examinations. We
      found that the insert was less suitable for MRI applications owing to severe RF
      shielding artefact. For spin-echo (SE), turbo spin-echo (TSE) and gradient-echo
      sequences, the reduction in signal-to-noise ratio (SNR) was as much as 89% when
      the insert was in place compared with the standard couch, making it less suitable
      as a patient-support material. Turning on the MultiTransmit switch together with
      using the scanner's quadrature body coil improved the reduction in SNR from 89%
      to 39% for the SE sequence and from 82% to 12% for the TSE sequence. CONCLUSION:
      No evidence was found to support reports in the literature that carbon fibre is
      an unsuitable material for use in MRI because of heating. ADVANCES IN KNOWLEDGE:
      This study suggests that carbon fibre is less suitable for large-scale MRI
      applications owing to it causing severe RF shading. Further research is needed to
      establish the suitability of the flatbed for treatment planning using alternative
      sequences or whether an alternative carbon fibre composite for large-scale MRI
      applications or a design that can minimize shielding can be found.

PMID- 27033183
TI  - During early to mid adolescence, moderate to vigorous physical activity is
      associated with restoring sleep, psychological functioning, mental toughness and
      male gender.
AB  - Numerous studies showed that regular physical activity (PA) is associated with
      both favourable and restorative sleep and improved psychological functioning
      (PF). However, there is little research on the topic covering the early to mid
      adolescence period. Moreover, curiosity and exploratory behaviour (CEB) and
      mental toughness (MT) as a result of PA remains thus far uninvestigated, as do
      possible gender differences. The aim of the present study was to explore the
      associations between PA, subjective sleep (sS), PF, CEB, and MT during early to
      mid-adolescence. A total of 1361 participants (mean age = 13.37 years; range: 11
      16 years; 51.2% female) took part in the study. They completed questionnaires
      covering PA, sS, PF, CEB, and MT. Greater PA was related to improved PF, better
      sS, and increased CEB and MT. Compared to male participants, females reported
      less PA, poorer sS, and had lower PF and MT scores. The present pattern of
      results suggests that during early and mid-adolescence greater PA was associated
      with more favourable sS and better PF, including CEB and MT, and that female
      participants reported lower scores in PA, sS, and PF. Accordingly, if PA has a
      favourable impact on sleep and psychological functioning, then data suggest that
      sports participation should be more tailored to increase motivation among female
      adolescents.

PMID- 27033184
TI  - Are Food Deserts Also Play Deserts?
AB  - Although food deserts are areas that lack easy access to food outlets and
      considered a barrier to a healthy diet and a healthy weight among residents, food
      deserts typically comprise older urban areas which may have many parks and street
      configurations that could facilitate more physical activity. However, other
      conditions may limit the use of available facilities in these areas. This paper
      assesses the use of parks in two Pittsburgh food desert neighborhoods by using
      systematic observation. We found that while the local parks were accessible, they
      were largely underutilized. We surveyed local residents and found that only a
      minority considered the parks unsafe for use during the day, but a substantial
      proportion suffered from health limitations that interfered with physical
      activity. Residents also felt that parks lacked programming and other amenities
      that could potentially draw more park users. Parks programming and equipment in
      food desert areas should be addressed to account for local preferences and
      adjusted to meet the needs and limitations of local residents, especially
      seniors.

PMID- 27033185
TI  - Can we Monitor a Patient with Inflammatory Bowel Disease and Adapt Treatment
      without Endoscopy?
AB  - BACKGROUND: While predictors of disease course in inflammatory bowel diseases
      (IBD) are not accurate, we adapt therapies reactively, after objective
      demonstration of the presence of active disease, complications, or an inadequate
      response to a therapeutic intervention. In this context, adequate monitoring is
      essential to make timely management decisions. OBJECTIVE: To review the role of
      clinical assessment, biomarkers, radiology and endoscopy in monitoring patients
      with IBD. RESULTS: Assessment of clinical symptoms is the cornerstone of
      monitoring in IBD; in ulcerative colitis (UC) there is acceptable correspondence
      between mucosal lesions and presence of symptoms, but in Crohn's disease (CD)
      there is a considerable disconnection between these two, and monitoring requires
      complementary tests. Blood and stool markers such as C-reactive protein and fecal
      calprotectin are increasingly used. However, the operating properties of these
      biomarkers are different according to disease type (UC vs. CD), age (pediatric or
      adult), and disease location (small bowel vs. colonic disease). Cross-sectional
      imaging has a similar accuracy to endoscopy to detect inflammation in CD, and a
      higher accuracy to detect stenosing and penetrating complications. It has also
      been shown that magnetic resonance imaging is accurate for measuring response to
      therapeutic interventions. CONCLUSION: Cross-sectional imaging is one of the
      preferred monitoring options in patients with CD. Endoscopy continues to be the
      preferred examination for assessing UC, and should still be considered in
      patients with CD who have symptoms or altered biomarkers and cross-sectional
      imaging is negative.

PMID- 27033186
TI  - Rational Design of Multi-Target Estrogen Receptors ERalpha and ERbeta by QSAR
      Approaches.
AB  - Estrogens play a crucial role in the growth, development, and homeostasis of
      various target tissues, their biological effects being mediated by the estrogen
      receptor (ER). In order to get a better understanding of the structural features
      of the modulators associated with the binding to ER, this paper provides an
      overview of the Quantitative Structure-Activity (QSAR) studies performed so far
      for estimating or predicting the activity of different ligands towards its two
      known subtypes (ERalpha and ERbeta). Recent progresses in the application of
      these modeling studies are additionally pointed out. Finally, ongoing challenges
      that may lead to new and exciting directions for QSAR modeling studies in this
      field are discussed.

PMID- 27033187
TI  - Modelling Chemotherapy-induced Cardiotoxicity by Human Pluripotent Stem Cells.
AB  - Novel antineoplastic therapies have greatly improved cancer survival;
      nevertheless they are bringing in new forms of cardiomyopathy, that can often
      limit proper cancer treatments. Novel cardioprotective therapies are therefore
      needed, for improving clinical outcomes in cancer patients. In order to test
      novel therapeutic strategies, there is an increasing need for appropriate
      experimental models of chemotherapy-induced cardiomyopathy. Induced pluripotent
      stem (iPS) cell- and human embryonic stem cell (hESC )-derived cardiomyocytes may
      be used as alternative in vitro models for studying mechanisms that underly
      chemotherapy-induced cardiomyopathy. In this review we discuss the use of iPS-
      and hESC-derived cardiomyocytes for evaluating additional pharmacological targets
      and for predicting chemotherapy-induced cardiotoxicity.

PMID- 27033188
TI  - The Role of MicroRNA in Pathogenesis and as Markers of HCV Chronic Infection.
AB  - Hepatitis C virus (HCV) is a worldwide major cause of chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma (HCC). Accumulating evidence indicates
      that a number of microRNAs (miRNAs), which are able to exert an effect on liver
      biology and pathology, can regulate or be regulated by HCV infection. Many
      studies demonstrate that HCV utilizes host miRNAs and modulates expression of
      miRNAs in infected hepatocytes for its infection and propagation. In turn, host
      miRNAs can directly regulate HCV replication through interaction with the HCV RNA
      genome or by indirectly controlling the host pathways associated with the virus
      replication, which eventually induce HCV-related liver diseases such as liver
      fibrosis, hepatic cirrhosis, or HCC. Recently, extracellular miRNAs (circulating
      miRNAs) detected in human serum and plasma are proposed as biomarker candidates
      for pathological conditions due to their remarkably stable nature and the non
      invasiveness of their detection. Since these circulating miRNAs exhibit
      consistent levels between healthy individuals but significantly changed profiles
      in disease conditions, considerable effort has been employed to investigate the
      alteration in the circulating miRNA pattern that is related with HCV infection
      and associated liver diseases. In this review, we summarize the features of
      miRNAs critical for HCVassociated liver disease initiation and progress, and
      discuss growing evidence that distinctive circulating miRNA patterns are related
      with HCV infection and associated liver diseases. These will shed light on the
      development of miRNA-based therapeutic modalities and non-invasive biomarkers for
      the diagnosis and prognosis of HCV infection and associated diseases.

PMID- 27033189
TI  - Smart Triggered Release in Controlled Drug Delivery.
AB  - BACKGROUND: Smart triggered release in controlled drug delivery has met an
      astonishing interest from the scientific community in the past few years due to
      the obvious medical benefits this type of systems represents. The reduction in
      toxicity due to a non-systemic administration is not the only reason for this
      increase, although it is a major reason for concern typically in anti-cancer
      therapy, but also the fact that some good therapeutic substances cannot be used
      either due to their high hydrophobicity or due to a very poor absorption at the
      required site of delivery. OBJECTIVE: This review article aims to highlight the
      efforts made by the scientific community in order to more efficiently trigger the
      drug payload at its destination, thus avoiding systemic exposure to the drug's
      toxic effect. RESULTS: In this review article several types of triggers have been
      evaluated, pH triggered delivery, thermally triggered delivery, REDOX change
      triggered delivery, as well as modifications made to trigger at a specific
      location based on the affinity of the receptors for a certain chemical moiety,
      such as folic acid. CONCLUSIONS: Through a proper nano-formulation the obstacles
      encountered by systemic delivery strategies can be circumvented, and through
      minor modifications hydrophobic drugs can be delivered through minor
      modifications to their structure, ensuring in the meantime that the therapeutic
      form is broken down by the human body's own internal systems. The main advantages
      in triggered drug delivery are the better healthcare strategy and the topical
      delivery, the main person winning in this case being the patient, the one person
      that should always be at the heart of the medical system.

PMID- 27033190
TI  - Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic
      Review.
AB  - Phytometabolites are functional elements derived from plants and most of them
      exhibit therapeutic characteristics such as anti-cancer, anti-inflammatory and
      anti-oxidant effects. Phytometabolites exert their anti-cancer effect by
      targeting multiple signaling pathways. One of the remarkable phenomena targeted
      by phytometabolites is the Warburg effect. The Warburg effect describes the
      observation that cancer cells exhibit an increased rate of glycolysis and
      aberrant redox activity compared to normal cells. This phenomenon promotes
      further cancer development and progression. Recent observations revealed that
      some phytometabolites could target metabolic-related enzymes (e.g. Hexokinase,
      Pyruvate kinase M2, HIF-1) in cancer cells, with little or no harm to normal
      cells. Since hyper-proliferation of cancer cells is fueled by higher cellular
      metabolism, phytometabolites targeting these metabolic pathways can create
      synergistic crosstalk with induced apoptotic pathways and sensitize cancer cells
      to chemotherapeutic agents. In this review, we discuss phytometabolites that
      target the Warburg effect and the underlying molecular mechanism that leads to
      tumor growth suppression.

PMID- 27033191
TI  - Smart Drug Delivery Systems in Cancer Therapy.
AB  - BACKGROUND: Smart nanocarriers have been designed for tissue-specific targeted
      drug delivery, sustained or triggered drug release and co-delivery of synergistic
      drug combinations to develop safer and more efficient therapeutics. OBJECTIVE:
      Advances in drug delivery systems provide reduced side effects, longer
      circulation half-life and improved pharmacokinetics. RESULTS: Smart drug delivery
      systems have been achieved successfully in the case of cancer. These nanocarriers
      can serve as an intelligent system by considering the differences of tumor
      microenvironment from healthy tissue, such as low pH, low oxygen level, or high
      enzymatic activity of matrix metalloproteinases. CONCLUSION: The performance of
      anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced
      cellular internalization of smart nanocarriers and controlled drug release. Here,
      we review targeting, cellular internalization; controlled drug release and
      toxicity of smart drug delivery systems. We are also emphasizing the stimulus
      responsive controlled drug release from smart nanocarriers.

PMID- 27033192
TI  - Nosocomial Infections and Antimicrobial Treatment in Coiled Patients with
      Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: Nosocomial infections are common in patients with spontaneous
      subarachnoid hemorrhage (SAH). The aim of this retrospective cohort study was to
      determine the incidence of infections during SAH and to evaluate the course of
      inflammation parameters and its implications for long term outcome. OBJECTIVE:
      Ninety-nine consecutive coiled SAH patients were included. Laboratory and
      clinical parameters as well as culture positive infections were followed over the
      disease course. Long-term outcome was assessed at 6-month by the Glasgow Outcome
      score (GOS) and dichotomized in favorable (GOS>3) and unfavorable outcome
      (GOS<=3). RESULTS: The most frequent infections were pulmonary (30.3%) urinary
      tract (25.3%), blood stream infections (20.2%) and ventriculitis (5.1%). The
      incidence of infections did not significantly differ between outcome groups. In
      contrast, patients with unfavorable outcome had a higher incidence of sepsis
      (46.7% versus 24.6%). C-reactive protein (CRP) and leukocytes were significantly
      higher in patients with unfavorable outcome. A CRP increase of 6 mg/dl or more in
      the first 3 days after SAH was independently associated with unfavorable outcome
      (OR 7.19 CI 1.7-30.52; p=0.008). Patients with an early CRP increase were more
      frequently treated with antimicrobial therapy in the first 3 days after admission
      which led to a significantly lower incidence of culture positive infections in
      the later course. CONCLUSION: A sharp CRP-increase in the acute phase of SAH
      could potentially aid the intensivist in the early identification of patients at
      high risk for neurological morbidity. Early antimicrobial treatment reduces the
      rate of patients showing culture positive infections in the course of the
      disease.

PMID- 27033193
TI  - Recent Advances in Nanosystems and Strategies for Managing Leishmaniasis.
AB  - BACKGROUND: Parasitic infection such as leishmaniasis, a neglected tropical
      disease, presents a significant global burden which is responsible for high
      mortality rate especially in less developed countries. Its intracellular nature
      and disseminated locations of parasite, limited number of chemotherapeutic
      agents, increasing incidences of resistance to first line drugs and toxicities,
      pose a great challenge to formulation scientists that have necessitated effective
      management of leishmanial infection by modulating the delivery of existing drugs.
      Over the past decade, research on development of alternative treatments such as
      nanotechnology-based drug delivery systems (nanoparticles, nanosuspensions,
      liposomes etc.), use of natural products as well as development of
      antileishmanial vaccine has been extensively investigated. OBJECTIVE: The present
      review focuses on different facets of therapeutic strategies, existing
      miscellaneous drug delivery systems and approaches intended for management, as
      well as treatment of the infection, with an objective to summarize the current
      trends and strategies adopted for antileishmanial therapy in a systematic manner.
      Moreover, the article encloses an eclectic collection of patents allied to new
      fangled chemotherapeutics for antileishmanial therapy. CONCLUSION: The reported
      miscellaneous novel drug delivery systems along with the diverse approaches are
      seem to be precise, secure and relatively effective; and in an outcome, could
      lead to the new track for management of leishmaniasis.

PMID- 27033194
TI  - ROCK in CNS: Different Roles of Isoforms and Therapeutic Target for
      Neurodegenerative Disorders.
AB  - Rho-associated protein kinase (ROCK) is a serine-threonine kinase originally
      identified as a crucial regulator of actin cytoskeleton. Recent studies have
      defined new functions of ROCK as a critical component of diverse signaling
      pathways in neurons. In addition, inhibition of ROCK causes several biological
      events such as increase of neurite outgrowth, axonal regeneration, and activation
      of prosurvival Akt. Thus, it has attracted scientist's strong attentions and
      considered ROCK as a promising therapeutic target for the treatment of
      neurodegenerative disorders including Alzheimer disease, Parkinson's disease,
      Huntington';s disease, multiple sclerosis, and amyotrophic lateral sclerosis.
      However, ROCK has two highly homologous isoforms, ROCK1 and ROCK2. Accumulated
      evidences indicate that ROCK1 and ROCK2 might involve in distinct cellular
      functions in central nervous system (CNS) and neurodegenerative processes. This
      review summarizes recent updates regarding ROCK isoformspecific functions in CNS
      and the progress of ROCK inhibitors in preclinical studies for neurodegenerative
      diseases.

PMID- 27033195
TI  - The Role of Statins in the Activation of Heme Oxygenase-1 in Cardiovascular
      Diseases.
AB  - Cardiovascular diseases (CVD) are associated with the dysfunction of endothelium
      that regulates the contractile state of vascular walls and cellular composition.
      Recent large clinical trials indicated that lipid-modifying interventions
      decrease the risk of CVD in patients with hypercholesterolemia and in those with
      relatively normal levels of LDL cholesterol. They also highlighted lipid
      independent role of well-established lipid-lowering drugs- statins- which inhibit
      3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and are used in the
      treatment of hypercholesterolemia and reduction of atherosclerosis. Novel
      therapeutic approaches of statins include their influence on heme oxygenase 1 (HO
      1) and HO-1 related signaling pathways such as activator protein (AP)-1, protein
      kinase G (PKG), extracellular matrix-regulated kinase (ERK), p38 MAPK or NFkappaB
      in vascular wall cells. This review aimed to describe the molecular mechanisms
      involved in the induction of HO-1 under different statins in the most common CVD.

PMID- 27033196
TI  - Advances in Drug Delivery Systems, from 0 to 3D superstructures.
AB  - BACKGROUND: Nanomedicine is currently exploited for manufacturing therapeutic DDS
      and treatments protocols for various diseases and disorders. To obtain DDS,
      different types of materials are used, from organic to inorganic, polar to non
      polar, micro to nanomaterials from 0D to 3D structured materials, respectively.
      Many of these materials were extensively studied and reviewed in the literature.
      OBJECTIVE: The objectives of this review is to make a clear overview on drug
      delivery systems depending several aspects related to delivery mechanisms, the
      type of supports, the active agents ant the potential applications in the
      prevention or treatment of various diseases. RESULTS: Following aspects are
      extensively debated: synthesis issues, characteristics and potential uses of 0,
      1, 2 and 3D drug delivery systems according to their nature and applications.
      These systems can be can be tailored according to the delivery mechanism (0-3D
      delivery) as well as by using more active agents, with more therapeutic activity
      or same activity but with different mechanisms of action. The size and morphology
      of the drug delivery system is essential, especially when talking about the
      internalization into the tumor cells while the mobility is especially dependent
      on the size. The influence of the nature of the supports and their polarity was
      extensively studied during the last decades, as well as the importance of the
      porosity and pore size, but only limited papers are devoted to the holistic
      analysis of the dimensionality of the support and the ways of delivering the
      active agents. CONCLUSION: This review is devoted to a holistic insight into the
      drug delivery systems, from a new, only marginally studied point of view, meaning
      the dimensionality of the drug delivery systems and the characteristics of the
      delivery.

PMID- 27033197
TI  - Withdrawn: Paroxysmal nocturnal haemoglobinuria from the prespective of
      paediatric haematologists.
AB  - Withdrawn by the publisher.

PMID- 27033198
TI  - Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope?
AB  - Oxidative stress is a pathological feature common to a multitude of neurological
      diseases. The production of reactive oxygen species (ROS) is the main mechanism
      underlying this cellular redox imbalance. Antioxidants protect biological targets
      against ROS, therefore, they have been considered as attractive potential
      therapeutic agents to counteract ROS-mediated neuronal damage. However, despite
      encouraging in vitro and preclinical in vivo data, the clinical efficacy of
      antioxidant treatment strategies is marginal and most clinical trials using
      antioxidants as therapeutic agents in neurodegenerative diseases have yielded
      disappointing outcomes. This might in part be due to the need of adjustment in
      concentrations and time parameters between preclinical studies and clinical
      settings. Moreover new efficient delivery methods need to be investigated,
      particularly taking into account that a successful therapeutic agent for
      neurological diseases should readily cross the blood-brain barrier (BBB). In that
      sense, the use of compounds that cross the BBB and boost the endogenous
      antioxidant defense machinery, by activating for instance the Nrf2 pathway, or
      compounds that are able to modulate ROS production, such as NOX enzyme
      inhibitors, seems to represent a more promising approach to combat oxidative
      stress in the central nervous system (CNS). Here we present a brief overview of
      the main players in oxidative stress and outline evidences of their involvement
      in Parkinson's disease, Alzheimer's disease, Huntington's disease and multiple
      sclerosis. Finally, we review and critically discuss the potential of
      antioxidants as therapeutics for central nervous system disorders with a special
      focus on emerging novel therapeutic strategies.

PMID- 27033199
TI  - Progress in Therapies for Myocardial Ischemia Reperfusion Injury.
AB  - BACKGROUND: Experimental studies of acute myocardial infarction have revealed
      that up to half of the final infarct size may be due to reperfusion injury rather
      than the initial ischemic incident. Research over the past three decades has
      deepened our understanding of the molecular mechanisms underlying ischemic
      reperfusion injury and several therapeutic strategies to decrease the incidence
      and severity of reperfusion injury have been explored. OBJECTIVE: To discuss the
      promising therapies and future perspectives on methods to attenuate myocardial
      reperfusion injury. RESULTS: Existing therapies that address reperfusion can be
      divided into two major groups comprising nonpharmacological and pharmacological
      interventions. Myriad pharmacological and nonpharmacological approaches to reduce
      lethal reperfusion injury have been employed. Although many initial clinical
      studies were negative, more recent proof-of-concept clinical trials are
      promising. To date, the most encouraging results are with ischemic
      postconditioning, remote ischemic preconditioning, ANP, adenosine, cyclosporine
      and exenatide. CONCLUSION: Studies demonstrate that nonpharmacological and
      pharmacological conditioning can be used together as part of a multifaceted
      approach to improve clinical outcomes in patients with ischemic heart disease.

PMID- 27033200
TI  - Highly efficient organic tandem solar cell with a SubPc interlayer based on
      TAPC:C70 bulk heterojunction.
AB  - We report a small molecule tandem organic photovoltaic (OPV) cell with a high
      power conversion efficiency (PCE) of 7.27%. This cell contains two subcells with
      an identical mixed active layer of C70:5 wt%TAPC (1,1-bis-(4-bis(4-methyl-phenyl)
      amino-phenyl)-cyclohexane). The performance was dramatically improved by simply
      inserting a thin boron subphthalocyanine chloride (SubPc) interlayer, which
      results in an increase of the short-circuit current and open-circuit voltage as
      well as a decrease of the series resistance of the tandem cell. The response of
      the cell only contributed from the absorption of C70. The high PCE was attributed
      to the high absorption efficiency of C70 and improved holes extraction efficiency
      at the anode due to the band bending occurs at both MoO3/SubPc and SubPc/C70:5
      wt%TAPC interfaces. 

PMID- 27033201
TI  - BIOMEX Experiment: Ultrastructural Alterations, Molecular Damage and Survival of
      the Fungus Cryomyces antarcticus after the Experiment Verification Tests.
AB  - The search for traces of extinct or extant life in extraterrestrial environments
      is one of the main goals for astrobiologists; due to their ability to withstand
      stress producing conditions, extremophiles are perfect candidates for
      astrobiological studies. The BIOMEX project aims to test the ability of
      biomolecules and cell components to preserve their stability under space and Mars
      like conditions, while at the same time investigating the survival capability of
      microorganisms. The experiment has been launched into space and is being exposed
      on the EXPOSE-R2 payload, outside of the International Space Station (ISS) over a
      time-span of 1.5 years. Along with a number of other extremophilic
      microorganisms, the Antarctic cryptoendolithic black fungus Cryomyces antarcticus
      CCFEE 515 has been included in the experiment. Before launch, dried colonies
      grown on Lunar and Martian regolith analogues were exposed to vacuum, irradiation
      and temperature cycles in ground based experiments (EVT1 and EVT2). Cultural and
      molecular tests revealed that the fungus survived on rock analogues under space
      and simulated Martian conditions, showing only slight ultra-structural and
      molecular damage.

PMID- 27033202
TI  - Hydroxylation of methane through component interactions in soluble methane
      monooxygenases.
AB  - Methane hydroxylation through methane monooxygenases (MMOs) is a key aspect due
      to their control of the carbon cycle in the ecology system and recent
      applications of methane gas in the field of bioenergy and bioremediation.
      Methanotropic bacteria perform a specific microbial conversion from methane, one
      of the most stable carbon compounds, to methanol through elaborate mechanisms.
      MMOs express particulate methane monooxygenase (pMMO) in most strains and soluble
      methane monooxygenase (sMMO) under copper-limited conditions. The mechanisms of
      MMO have been widely studied from sMMO belonging to the bacterial multicomponent
      monooxygenase (BMM) superfamily. This enzyme has diiron active sites where
      different types of hydrocarbons are oxidized through orchestrated hydroxylase,
      regulatory and reductase components for precise control of hydrocarbons, oxygen,
      protons, and electrons. Recent advances in biophysical studies, including
      structural and enzymatic achievements for sMMO, have explained component
      interactions, substrate pathways, and intermediates of sMMO. In this account,
      oxidation of methane in sMMO is discussed with recent progress that is critical
      for understanding the microbial applications of C-H activation in one-carbon
      substrates. 

PMID- 27033203
TI  - Hymenobacter sedentarius sp. nov., isolated from a soil.
AB  - A novel Gram-negative and red-pinkish bacterium designated DG5B(T) was isolated
      from a dry soil. Cells were rods that were catalase- and oxidase-positive, and
      non-motile. The strain was found to grow at temperatures from 10 to 30 degrees C
      (optimum 25 degrees C) and pH 6.0-8.0, (optimum pH 7) on R2A broth. 16S rRNA gene
      sequence (1,452 bp) analysis of this strain identified it as a member of the
      genus Hymenobacter that belongs to the class Cytophagia. The highest gene
      sequence similarities were with Hymenobacter arizonensis OR362-8(T) (98.3%),
      Hymenobacter humi DG31A(T) (97.6%), and Hymenobacter glaciei VUG-A130(T) (96.6%).
      Strain DG5B(T) exhibited <70% DNA-DNA relatedness with H. arizonensis (34.7 +/-
      7.0%; reciprocally, 29.7 +/- 1.2%) and H. humi (39.4 +/- 4.3%; reciprocally, 39.5
      +/- 3.3%) as a different genomic species, and its genomic DNA G+C content was
      59.8%. Strain DG5B(T) had the following chemotaxonomic characteristics: the major
      fatty acids are iso-C15:0, anteiso-C15:0, C16:1 omega5c, and summed feature 3
      (C16:1 omega7c / C16:1 omega6c); polar lipid profile contained
      phosphatidylethanolamine (PE), unknown aminophospholipid (APL), unknown
      glycolipids (GL), unknown phospholipids (PL), and unknown polar lipids (L); the
      major quinone is MK-7. The absorbance peak of pigment is at 481.0 nm. Strain
      DG5B(T) showed low-level resistance to gamma-ray irradiation. Phenotypic,
      chemotaxonomic, and genotypic properties indicated that isolate DG5B(T)
      represents a novel species within the genus Hymenobacter for which the name
      Hymenobacter sedentarius sp. nov. is proposed. The type strain is DG5B(T) (=KCTC
      32524(T) =JCM 19636(T)). 

PMID- 27033204
TI  - Species identity of Phellinus linteus (sanghuang) extensively used as a medicinal
      mushroom in Korea.
AB  - Sanghuang is a medicinal mushroom that has gained particular attention in Korea.
      It has been extensively studied for the past few decades as a natural immune
      booster and cancer suppressor. Although the scientific name, Phellinus linteus,
      has been commonly used to refer to the sanghuang mushroom, the species identity
      of sanghuang has been called into question due to the ambiguity of its
      circumscription and the inadequacy of morphological distinctions within allied
      species. Because the species concept of sanghuang has been elucidated by recent
      molecular phylogenetic studies, it has become necessary to clarify the taxonomic
      positions of sanghuang strains extensively utilized in Korea. We conducted a
      phylogenetic analysis of 74 strains belonging to the P. linteus-baumii complex
      based on ITS nrDNA sequences. Parental stains of sanghuang varieties formally
      registered in the Korea Seed & Variety Service, including ASI 26046 (Corea
      sanghuang), 26114 (Boolro), and 26115 (HK 1-ho) were grouped with Sanghuangporus
      sanghuang instead of P. linteus in the inferred phylogeny. 

PMID- 27033205
TI  - Uncultured bacterial diversity in a seawater recirculating aquaculture system
      revealed by 16S rRNA gene amplicon sequencing.
AB  - Bacterial diversity in a seawater recirculating aquaculture system (RAS) was
      investigated using 16S rRNA amplicon sequencing to understand the roles of
      bacterial communities in the system. The RAS was operated at nine different
      combinations of temperature (15 degrees C, 20 degrees C, and 25 degrees C) and
      salinity (200/00, 250/00, and 32.50/00). Samples were collected from five or six
      RAS tanks (biofilters) for each condition. Fifty samples were analyzed.
      Proteobacteria and Bacteroidetes were most common (sum of both phyla: 67.2% to
      99.4%) and were inversely proportional to each other. Bacteria that were present
      at an average of >= 1% included Actinobacteria (2.9%) Planctomycetes (2.0%),
      Nitrospirae (1.5%), and Acidobacteria (1.0%); they were preferentially present in
      packed bed biofilters, mesh biofilters, and maturation biofilters. The three
      biofilters showed higher diversity than other RAS tanks (aerated biofilters,
      floating bed biofilters, and fish tanks) from phylum to operational taxonomic
      unit (OTU) level. Samples were clustered into several groups based on the
      bacterial communities. Major taxonomic groups related to family Rhodobacteraceae
      and Flavobacteriaceae were distributed widely in the samples. Several taxonomic
      groups like [Saprospiraceae], Cytophagaceae, Octadecabacter, and Marivita showed
      a cluster-oriented distribution. Phaeobacter and Sediminicola-related reads were
      detected frequently and abundantly at low temperature. Nitrifying bacteria were
      detected frequently and abundantly in the three biofilters. Phylogenetic analysis
      of the nitrifying bacteria showed several similar OTUs were observed widely
      through the biofilters. The diverse bacterial communities and the minor taxonomic
      groups, except for Proteobacteria and Bacteroidetes, seemed to play important
      roles and seemed necessary for nitrifying activity in the RAS, especially in
      packed bed biofilters, mesh biofilters, and maturation biofilters. 

PMID- 27033206
TI  - Effects of blue light on pigment biosynthesis of Monascus.
AB  - The influence of different illumination levels of blue light on the growth and
      intracellular pigment yields of Monascus strain M9 was investigated. Compared
      with darkness, constant exposure to blue light of 100 lux reduced the yields of
      six pigments, namely, rubropunctatamine (RUM), monascorubramine (MOM),
      rubropunctatin (RUN), monascorubrin (MON), monascin (MS), and ankaflavin (AK).
      However, exposure to varying levels of blue light had different effects on
      pigment production. Exposure to 100 lux of blue light once for 30 min/day and to
      100 lux of blue light once and twice for 15 min/day could enhance RUM, MOM, MS,
      and AK production and reduce RUN and MON compared with non-exposure. Exposure to
      100 lux twice for 30 min/day and to 200 lux once for 45 min/day decreased the
      RUM, MOM, MS, and AK yields and increased the RUN and MON. Meanwhile, the
      expression levels of pigment biosynthetic genes were analyzed by real-time
      quantitative PCR. Results indicated that gene MpPKS5, mppR1, mppA, mppB, mmpC,
      mppD, MpFasA, MpFasB, and mppF were positively correlated with the yields of RUN
      and MON, whereas mppE and mppR2 were associated with RUM, MOM, MS, and AK
      production. 

PMID- 27033207
TI  - Structural insight for substrate tolerance to 2-deoxyribose-5-phosphate aldolase
      from the pathogen Streptococcus suis.
AB  - 2-deoxyribose-5-phosphate aldolase (DERA) is a class I aldolase that catalyzes
      aldol condensation of two aldehydes in the active site, which is particularly
      germane in drug manufacture. Structural and biochemical studies have shown that
      the active site of DERA is typically loosely packed and displays broader
      substrate specificity despite sharing conserved folding architecture with other
      aldolases. The most distinctive structural feature of DERA compared to other
      aldolases is short and flexible C-terminal region. This region is also
      responsible for substrate recognition. Therefore, substrate tolerance may be
      related to the C-terminal structural features of DERA. Here, we determined the
      crystal structures of full length and C-terminal truncated DERA from
      Streptococcus suis (SsDERA). In common, both contained the typical (alpha/beta)8
      TIM-barrel fold of class I aldolases. Surprisingly, C-terminal truncation
      resulting in missing the last alpha9 and beta8 secondary elements, allowed DERA
      to maintain activity comparable to the fulllength enzyme. Specifically, Arg186
      and Ser205 residues at the C-terminus appeared mutually supplemental or less
      indispensible for substrate phosphate moiety recognition. Our results suggest
      that DERA might adopt a shorter C-terminal region than conventional aldolases
      during evolution pathway, resulting in a broader range of substrate tolerance
      through active site flexibility. 

PMID- 27033208
TI  - Antibacterial effects of N-acetylcysteine against endodontic pathogens.
AB  - The success of endodontic treatment depends on the eradication of microorganisms
      from the root canal system and the prevention of reinfection. The purpose of this
      investigation was to evaluate the antibacterial and antibiofilm efficacy of N
      acetylcysteine (NAC), an antioxidant mucolytic agent, as an intracanal medicament
      against selected endodontic pathogens. Minimum inhibitory concentrations (MICs)
      of NAC for Actinomyces naeslundii, Lactobacillus salivarius, Streptococcus
      mutans, and Enterococcus faecalis were determined using the broth microdilution
      method. NAC showed antibacterial activity, with MIC values of 0.78-1.56 mg/ml.
      The effect of NAC on biofilm formation of each bacterium and a multispecies
      culture consisting of the four bacterial species was assessed by crystal violet
      staining. NAC significantly inhibited biofilm formation by all the monospecies
      and multispecies bacteria at minimum concentrations of 0.78-3.13 mg/ml. The
      efficacy of NAC for biofilm disruption was evaluated by scanning electron
      microscopy and ATP-bioluminescence quantification using mature multispecies
      biofilms. Preformed mature multispecies biofilms on saliva-coated hydroxyapatite
      disks were disrupted within 10 min by treatment with NAC at concentrations of 25
      mg/ml or higher. After 24 h of treatment, the viability of mature biofilms was
      reduced by > 99% compared with the control. Moreover, the biofilm disrupting
      activity of NAC was significantly higher than that of saturated calcium hydroxide
      or 2% chlorhexidine solution. Within the limitations of this in vitro study, we
      conclude that NAC has excellent antibacterial and antibiofilm efficacy against
      endodontic pathogens and may be used as an alternative intracanal medicament in
      root canal therapies. 

PMID- 27033209
TI  - A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host
      macrophages infected with Mycobacterium tuberculosis.
AB  - Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival
      pathways. Some studies indicated that the expression of Mcl-1 was upregulated in
      host cells during infection with the virulent Mycobacterium tuberculosis strain,
      H37Rv. The present study was designed to investigate the effect of inhibiting Mcl
      1 expression both in vivo and in vitro on apoptosis of host macrophages infected
      with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected
      by the real time-polymerase chain reaction, western blotting, and
      immunohistochemistry. Flow cytometry and transmission electron microscopy were
      used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host
      macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was
      downregulated efficiently in H37Rv-infected host macrophages using shRNA.
      Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host
      macrophages significantly. The increased apoptosis correlated with a decrease in
      M. tuberculosis colony forming units recovered from H37Rv-infected cells that
      were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced
      accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the
      pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed
      that specific knockdown of Mcl-1 expression increased apoptosis of host
      macrophages significantly and decreased the intracellular survival of a virulent
      strain of M. tuberculosis. These data indicate that interference with Mcl-1
      expression may provide a new avenue for tuberculosis therapy. 

PMID- 27033210
TI  - Structural and functional characterization of an iron-sulfur cluster assembly
      scaffold protein-SufA from Plasmodium vivax.
AB  - Iron-sulfur (Fe-S) clusters are utilized as prosthetic groups in all living
      organisms for diverse range of cellular processes including electron transport in
      respiration and photosynthesis, sensing of ambient conditions, regulation of gene
      expression and catalysis. In Plasmodium, two Fe-S cluster biogenesis pathways are
      reported, of which the Suf pathway in the apicoplast has been shown essential for
      the erythrocytic stages of the parasite. While the initial components of this
      pathway detailing the sulfur mobilization have been elucidated, the components
      required for the assembly and transfer of Fe-S clusters are not reported from the
      parasite. In Escherichia coli, SufB acts as a scaffold protein and SufA traffics
      the assembled Fe-S cluster from SufB to target apo-proteins. However, in
      Plasmodium, the homologs of these proteins are yet to be characterized for their
      function. Here, we report a putative SufA protein from Plasmodium vivax with
      signature motifs of A-type scaffold proteins, which is evolutionarily conserved.
      The presence of the [Fe4S4](3+) cluster under reduced conditions was confirmed by
      UV-visible and EPR spectroscopy and the interaction of these clusters with the
      conserved cysteine residues of chains A and B of PvSufA, validates its existence
      as a dimer, similar to that in E. coli. The H-bond interactions at the PvSufA
      SufB interface demonstrate SufA as a scaffold protein in conjunction with SufB
      for the pre-assembly of Fe-S clusters and their transfer to the target proteins.
      Co-localization of the protein to the apicoplast further provides an experimental
      evidence of a functional scaffold protein SufA for the biogenesis of Fe-S
      clusters in apicoplast of Plasmodium.

PMID- 27033211
TI  - ATMPs for Cancer Immunotherapy: A Regulatory Overview.
AB  - This chapter discusses European regulatory requirements for development of
      advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches,
      describing the framework for clinical trials and for marketing
      authorization.Regulatory critical issues and challenges for developing ATMP are
      also discussed, with focus on potency determination, long-term follow-up,
      comparability, and insertional mutagenesis issues. Some of the most critical
      features of GMP application to ATMP are also described. 

PMID- 27033212
TI  - Natural Antibodies to Tumor-Associated Antigens.
AB  - Natural autoantibodies raised by humoral immune response to cancer can be
      exploited to identify potential tumor-associated antigens (TAAs), and might
      constitute new putative prognostic and/or diagnostic biomarkers. Here we describe
      how sera from tumor patients can be used to identify TAAs by screening antibody
      immunoreactivity against the cancer proteome resolved by two-dimensional gel
      electrophoresis. 

PMID- 27033213
TI  - Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded
      Dendritic Cell Vaccines for Cancer Immunotherapy.
AB  - First described in the 1970s, dendritic cells (DC) are currently subjects of
      intense investigation to exploit their unique antigen-presenting and
      immunoregulatory capacities. In cancer, DC show promise to elicit or amplify
      immune responses directed against cancer cells by activating natural killer (NK)
      cells and tumor antigen-specific T cells. Wilms' tumor 1 (WT1) protein is a tumor
      associated antigen that is expressed in a majority of cancer types and has been
      designated as an antigen of major interest to be targeted in clinical cancer
      immunotherapy trials. In this chapter, we describe the generation,
      cryopreservation, and thawing of clinical grade autologous monocyte-derived DC
      vaccines that are loaded with WT1 by messenger RNA (mRNA) electroporation. This
      in-house-developed transfection method gives rise to presentation of multiple
      antigen epitopes and can be used for all patients without restriction of human
      leukocyte antigen (HLA) type.

PMID- 27033214
TI  - Quantitative and Qualitative Analysis of Tumor-Associated CD4+ T Cells.
AB  - CD4(+) T cells comprise a significant portion of tumor-infiltrating lymphocytes.
      Different subsets of CD4(+) T cells exist and they exert different effector
      functions in tumor immunity depending on the cytokines produced going from
      antitumor to pro-tumor. Methods that use small aliquots of cells to identify ex
      vivo the frequency and functional orientation of tumor-specific CD4(+) T cells in
      the blood and visualization of the presence of different CD4(+) T cell subsets
      and their localization at the tumor site are valuable tools to determine their
      clinical impact in neoplastic diseases. 

PMID- 27033215
TI  - Detection and Functional Analysis of Tumor-Derived LXR Ligands.
AB  - There is growing evidence highlighting the ability of nuclear receptors to
      control not only metabolism, but also inflammation and cancer progression. In
      particular liver X receptors (LXRs), the nuclear receptors physiologically
      involved in cholesterol homeostasis, have been shown to regulate innate and
      adaptive immune responses in many pathological conditions, including cancer.We
      have recently demonstrated that LXR ligands (oxysterols) released by tumor cells
      may have an immunomodulatory role, affecting the immune cells involved in the
      antitumor immune response. Indeed, oxysterols inhibit the expression of the
      chemokine receptor CCR7 on dendritic cells (DC) in an LXR-dependent manner, thus
      impairing DC migration to secondary lymphoid organs, and therefore dampening the
      induction of successful antitumor responses.We have resorted to direct (i.e.,
      luciferase-based LXR activation assay) and indirect (i.e., activation of LXR
      target genes in dendritic cells) methods in order to assess the presence of LXR
      ligands (oxysterols) in tumor-conditioned media.These two methods are also
      suitable to study strategies to block oxysterol release by tumor cells. 

PMID- 27033216
TI  - In Vitro Generation of Antigen-Specific T Cells from Induced Pluripotent Stem
      Cells of Antigen-Specific T Cell Origin.
AB  - Induced pluripotent stem (iPS) cells derived from T lymphocyte (T-iPS cells)
      preserve the T cell receptor (TCR) alpha and beta gene rearrangements identical
      to the original T cell clone. Re-differentiated CD8 single positive alphabeta T
      cells from the T-iPS cells exhibited antigen-specific cytotoxicity, improved
      proliferative response, and elongation of telomere indicating rejuvenation of
      antigen specific T cell immunity in vitro. To regenerate antigen specific
      cytotoxic T lymphocytes (CTL), first, we have optimized a method for
      reprogramming-resistant CD8 T cell clones into T-iPS cells by using sendaiviral
      vectors. Second, we have optimized stepwise differentiation methods for inducing
      hematopoietic progenitor cells, T cell progenitors, and functionally matured CD8
      single positive CTL. These protocols provide useful in vitro tools and models
      both for research of antigen-specific T cell immunotherapy and for research of
      normal and pathological thymopoiesis. 

PMID- 27033217
TI  - Chimeric Antigen Receptors for Cancer Immunotherapy.
AB  - The adoptive transfer of T lymphocytes expressing chimeric antigen receptors
      (CARs) has emerged as a promising treatment for various lymphoid and solid
      malignancies. Patients treated with CAR-T cells have achieved dramatic responses
      and in some cases, complete tumor eradication. Given that CARs combine the
      specificity of a monoclonal antibody with the internal signaling domains of T
      cells, there is flexibility for choice of target antigen and strength of T-cell
      activation. This targeting mechanism also relinquishes the need for antigen
      processing and presentation via the major histocompatibility complex (MHC),
      making CARs a very attractive therapeutic option for the majority of patients.
      This review describes current methodological strategies used to generate CAR
      molecules, how to insert these molecules in T lymphocytes and how to evaluate the
      functionality of these CAR-T cells using various in vitro and in vivo
      experiments. 

PMID- 27033218
TI  - Cancer and Chemokines.
AB  - Chemokines are a large family of secreted cytokines whose main function is to
      mediate leukocyte directional migration. Most cancers contain chemokines and
      express chemokine receptors as a consequence of the activity of deregulated
      transcription factors or tumor-suppressor genes. Indeed chemokines expression at
      the tumor site dictates leukocyte infiltration and angiogenesis, while chemokine
      receptors expression by tumor cells promotes their growth and matastatization.
      Chemokines also have several indirect effects on tumor growth and are a relevant
      element in the cancer-related inflammation. In this chapter we will describe
      technical approaches available to study the role of chemokines in leukocyte
      infiltration and tumor metastatization in murine tumor models. 

PMID- 27033219
TI  - T Cells as Antigen Carriers for Anti-tumor Vaccination.
AB  - The exploitation of the physiologic processing and presenting machinery of
      dendritic cells (DCs) by in vivo loading of tumor-associated antigens may improve
      the immunogenic potential and clinical efficacy of DC-based cancer vaccines. The
      approach developed by our group was based on the clinical observation that some
      patients treated with the infusion of donor lymphocytes transduced to express the
      HSV-TK suicide gene for relapse of hematologic malignancies, after allogeneic
      hematopoietic stem cell transplantation, developed a T cell-mediated immune
      response specifically directed against the HSV-TK gene product.We demonstrated
      that lymphocytes genetically modified to express HSV-TK as well as self/tumor
      antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor
      bearing mice. The infusion of TRP-2-transduced lymphocytes induced the
      establishment of protective immunity and long-term memory in tumor-bearing mice
      by cross-presentation of the antigen mediated by the CD11c(+)CD8a(+) DCs subset.
      A similar approach was applied in a clinical setting. Ten patients affected by
      MAGE-3(+) metastatic melanoma were treated with autologous lymphocytes
      retrovirally transduced to express the MAGE-3 tumor antigen. In three patients,
      the treatment led to the increase of MAGE-3 specific CD8+ and CD4+ effectors and
      the development of long-term memory, which ultimately correlated with a favorable
      clinical outcome. Transduced lymphocytes represent an efficient way for in vivo
      loading of tumor-associated antigens of DCs. 

PMID- 27033220
TI  - Exploiting Secreted Luciferases to Monitor Tumor Progression In Vivo.
AB  - Secreted luciferases provide a simple, accurate, and cost-effective tool to
      monitor tumor response after treatment in small animal models. This protocol
      describes all the steps required to generate human tumor cell lines expressing
      this reporter gene and to monitor in vivo tumor progression after injection in
      immunocompromised mice by means of serial peripheral blood sampling and analysis.

PMID- 27033221
TI  - Efficient RNA Interference of Primary Leukemic Cells for Loss-of-Function Studies
      in Xenograft Mouse Models.
AB  - RNA interference (RNAi) is a powerful tool for efficient and highly specific gene
      silencing. Transduction with lentiviral vectors provides stable and long-term
      gene expression in slowly and non-dividing cells. This chapter describes how to
      couple these two technologies to efficiently silence specific genes in primary
      acute myeloid leukemia (AML) cells for subsequent xenotransplantation in
      immunocompromised mice. This approach could be used for loss-of-function studies
      aimed at identifying oncogenic targets in AML.

PMID- 27033222
TI  - Modeling Human Graft-Versus-Host Disease in Immunocompromised Mice.
AB  - Hematopoietic stem cell transplantation (HSCT) from an allogeneic donor is an
      effective form of cancer immunotherapy, especially for acute leukemias. HSCT is
      however frequently complicated by the occurrence of graft-versus-host disease
      (GVHD). Immunocompromised mice infused with human T cells often develop a
      clinical syndrome resembling human GVHD (xenogeneic or X-GVHD). Herein, we
      describe a method for inducing X-GVHD in a highly reproducible manner. Given the
      human nature of immune effectors, this xenogeneic model can be routinely adopted
      for screening the efficacy of new treatments for GVHD. 

PMID- 27033223
TI  - ICOS Expression as Immunologic Marker in Immune Activating Monoclonal Antibodies.
AB  - Compelling experimental evidences point to monitoring of the absolute number of
      circulating ICOS-positive T cells as an early predictive marker of clinical
      activity of anti-CTLA-4 antibodies in cancer patients. Here, we report available
      data focusing on this issue and operative procedures to detect ICOS expression on
      circulating peripheral blood mononuclear cells during CTLA-4 blockade therapy. 

PMID- 27033224
TI  - Identifying NK Alloreactive Donors for Haploidentical Hematopoietic Stem Cell
      Transplantation.
AB  - NK cell alloreactivity mediated by donor NK cells is a fundamental therapeutic
      tool in HLA haplotype mismatched hematopoietic transplantation in adult acute
      myeloid leukemia and pediatric acute lymphoblastic leukemias. NK cell is mediated
      by donor NK cells recovering very early after transplant. The self donor KIR
      ligands educates the donor NK repertoire and arms functional NK cells which
      express inhibitory killer cell immunoglobulin-like receptor(s) (KIRs) for self
      class I ligand(s), They sense missing expression of donor KIR ligand(s) in the
      recipient and mediate alloreactivity. Donor-versus-recipient NK cell
      alloreactivity is evaluated by KIR genotyping and phenotyping and functional
      assay.

PMID- 27033225
TI  - Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of
      Cancer Immunotherapies.
AB  - Cellular immunotherapy targeting human tumor antigens is a promising strategy to
      treat solid tumors. Yet clinical results of cellular immunotherapy are
      disappointing. Moreover, the currently available in vitro human tumor models are
      not designed to study the optimization of T-cell therapies of solid tumors. Here,
      we describe a novel assay for multiparametric in situ analysis of therapeutic
      effects on individual human three-dimensional (3D) tumors. In this assay, tumors
      of several millimeter diameter are generated from human cancer cell lines of
      different tumor entities in a collagen type I microenvironment. A newly developed
      approach for efficient morphological analysis reveals that these in vitro tumors
      resemble many characteristics of the corresponding clinical cancers such as
      histological features, immunohistochemical staining patterns, distinct tumor
      growth compartments and heterogeneous protein expression. To assess the response
      to therapy with tumor antigen specific T-cells, standardized protocols are
      described to determine T-cell infiltration and tumor destruction by monitoring
      soluble factors and tumor growth. Human tumors engineered in 3D collagen
      scaffolds are excellent in vitro surrogates for avascular tumor stages allowing
      integrated analyses of the antitumor efficacy of cancer specific immunotherapy in
      situ. 

PMID- 27033227
TI  - [Cataract development after electrical injury].
AB  - Cataract development is one of the most common complications of ocular electrical
      injury. Our patient reported an electrical injury of his face 13 years ago that
      affected both eyes. Since that time he noticed progressive visual impairment of
      both eyes. At the time of first presentation in 2014, slit lamp examination
      showed characteristic opacities within the anterior and posterior subcapsular
      area of the lens. Cataract surgery led to full recovery of visual acuity.

PMID- 27033226
TI  - Glass hybrid, but not calcium hydroxide, remineralized artificial residual caries
      lesions in vitro.
AB  - OBJECTIVES: For deep carious lesions, less invasive carious tissue removal is
      recommended. The resulting residual carious lesions might benefit from
      remineralization by lining or restoration materials. We aimed to compare mineral
      gains in artificial residual lesions provided by calcium hydroxide and glass
      hybrid materials in combination with pulpal fluid simulation. METHODS: On the
      coronal aspect of human dentin discs (n = 20), artificial carious lesions were
      induced using acetic acid. Median mineral loss DeltaZ [25th/75th percentiles] of
      resulting lesions was 1643 [1301/1858] vol% MUm. One third of each disc served as
      baseline sample. The remaining disc was divided into four groups, each being
      covered with one experimental material (n = 20/group): flowable composite
      (control (CO)), setting or non-setting calcium hydroxide liner plus flowable
      composite (CH-S, CH-NS), and glass hybrid (GH). Samples were mounted in a dual
      chamber device. Pulpal surfaces were exposed to simulated pulpal fluid at 2.94
      kPa. Coronal surfaces were exposed to artificial saliva and rinsed with 200 ppm
      NaF every 2 weeks. After 12 weeks, mineral loss differences (DeltaDeltaZ) were
      assessed using transverse microradiography. Electron probe microscopic analysis
      was used to measure fluoride and strontium concentrations. RESULTS: Mineral gains
      were not significantly different between CO (DeltaDeltaZ = 372 [115/501] vol%
      MUm), CH-S (DeltaDeltaZ = 317 [229/919] vol% MUm), or CH-NS (DeltaDeltaZ = 292
      [130/579] vol% MUm; p > 0.05/Wilcoxon test) but significantly increased in GH
      (DeltaDeltaZ = 1044 [751/1264] vol% MUm, p < 0.001). Samples in GH showed
      fluoride and strontium enrichment deep into the dentin. Such enrichment was not
      found in CO. CONCLUSIONS: Within the limitations of this study, GH, but not
      calcium hydroxide, provided coronal remineralization of residual carious lesions.
      CLINICAL RELEVANCE: Glass hybrids might provide additional remineralization of
      residual carious lesions. The functional implications of this mineral gain need
      to be evaluated.

PMID- 27033228
TI  - [Nodular eyelid margin and lip tumors without MEN2b syndrome in a 29 year old
      man].
AB  - Neuromas of the eyelid margin and lower lip were diagnosed in a 29-year-old man.
      As the combination of these lesions is indicative of multiple endocrine neoplasia
      type 2b (MEN2b) syndrome, the presence of a medullary thyroid carcinoma or a
      pheochromocytoma were excluded by a systematic work-up. A mutation in the RET
      proto-oncogene was not found by genetic testing. In summary, the patient
      presented with neuromas on the eyelid margin and lower lip without an association
      to a syndrome; however, patients with such neuromas should be screened for MEN2b
      syndrome due to the high mortality.

PMID- 27033229
TI  - Cross-cultural adaptation and validation of the Italian version of the Western
      Ontario Osteoarthritis of the Shoulder index (WOOS).
AB  - BACKGROUND: The Western Ontario Osteoarthritis of the Shoulder index (WOOS) has
      been introduced as a disease-specific quality of life measurement in patients
      with glenohumeral arthritis. The aim of the present study was to perform a cross
      cultural adaptation of the English version of the WOOS to Italian and to assess
      its validity, reliability and responsiveness in patients with glenohumeral joint
      osteoarthritis treated conservatively. MATERIAL AND METHODS: The adaptation
      process was carried out following the simplified Guillemin criteria. The English
      version was translated into Italian by two bilingual orthopaedic surgeons and
      then translated back into English by two different bilingual orthopaedic
      surgeons. The original version was compared with the back-translation. The
      questionnaire was prospectively administered to 30 patients with glenohumeral
      osteoarthritis at baseline and again after 5 days for retest reliability. After 6
      months of conservative treatment, the responsiveness of the questionnaire was
      assessed in a subsample of 20 patients. The level of statistical significance was
      set at 0.05. RESULTS: The interclass correlation coefficient between test and
      retest of the WOOS was 0.99 (P < 0.001). Pearson's correlation coefficient
      between the WOOS and disability of the arm, shoulder and hand (DASH)
      preoperatively was 0.73 (P < 0.01) and the correlation between the changes of
      score for the WOOS and DASH was 0.75 (P < 0.01). There were no floor or ceiling
      effects. Responsiveness, calculated by standardized response mean, was 1.1 and
      effect size was 1.3. CONCLUSIONS: The Italian version of the WOOS questionnaire
      has shown to be equivalent to its English version and demonstrated good validity,
      reliability and responsiveness to conservative treatment of glenohumeral
      osteoarthritis. LEVEL OF EVIDENCE: Level II.

PMID- 27033230
TI  - From global to local: exploring the relationship between parameters and behaviors
      in models of electrical excitability.
AB  - Models of electrical activity in excitable cells involve nonlinear interactions
      between many ionic currents. Changing parameters in these models can produce a
      variety of activity patterns with sometimes unexpected effects. Further more,
      introducing new currents will have different effects depending on the initial
      parameter set. In this study we combined global sampling of parameter space and
      local analysis of representative parameter sets in a pituitary cell model to
      understand the effects of adding K (+) conductances, which mediate some effects
      of hormone action on these cells. Global sampling ensured that the effects of
      introducing K (+) conductances were captured across a wide variety of contexts of
      model parameters. For each type of K (+) conductance we determined the types of
      behavioral transition that it evoked. Some transitions were counterintuitive, and
      may have been missed without the use of global sampling. In general, the wide
      range of transitions that occurred when the same current was applied to the model
      cell at different locations in parameter space highlight the challenge of making
      accurate model predictions in light of cell-to-cell heterogeneity. Finally, we
      used bifurcation analysis and fast/slow analysis to investigate why specific
      transitions occur in representative individual models. This approach relies on
      the use of a graphics processing unit (GPU) to quickly map parameter space to
      model behavior and identify parameter sets for further analysis. Acceleration
      with modern low-cost GPUs is particularly well suited to exploring the moderate
      sized (5-20) parameter spaces of excitable cell and signaling models.

PMID- 27033231
TI  - Polymorphism 2184A/G in the AGER gene is not associated with diabetic retinopathy
      in Han Chinese patients with type 2 diabetes.
AB  - OBJECTIVE: To assess the association between the 2184A/G polymorphism in the
      advanced glycosylation end product-specific receptor (AGER) gene and the
      susceptibility to diabetic retinopathy (DR) in Han Chinese patients with type 2
      diabetes mellitus (T2DM). METHODS: This cross-sectional genotyping study included
      patients with T2DM with and without DR. Genotype and allele frequencies of the
      2184A/G polymorphism were detected using polymerase chain reaction-restriction
      fragment-length polymorphism analysis. RESULTS: This study included 943 patients
      with T2DM (285 with DR [DR group] and 658 without DR [NDR group]). There were no
      significant differences in age, sex, body mass index, total cholesterol, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol, diastolic
      blood pressure, glycosylated haemoglobin, fasting blood glucose, postprandial 2
      hour blood glucose, and triglycerides between the two groups. The duration of
      T2DM and systolic blood pressure were significantly increased in the DR group
      compared with the NDR group. No significant differences were found in allele (A
      and G) and genotype (AA, AG and GG) frequencies of the 2184A/G polymorphism
      between the two groups. CONCLUSION: The 2184A/G polymorphism in the AGER gene is
      not associated with DR in Han Chinese patients with T2DM.

PMID- 27033232
TI  - Developmental Hypothyroxinemia and Hypothyroidism Reduce Parallel Fiber-Purkinje
      Cell Synapses in Rat Offspring by Downregulation of Neurexin1/Cbln1/GluD2
      Tripartite Complex.
AB  - Iodine is a significant micronutrient. Iodine deficiency (ID)-induced
      hypothyroxinemia and hypothyroidism during developmental period can cause
      cerebellar dysfunction. However, mechanisms are still unclear. Therefore, the
      present research aims to study effects of developmental hypothyroxinemia caused
      by mild ID and hypothyroidism caused by severe ID or methimazole (MMZ) on
      parallel fiber-Purkinje cell (PF-PC) synapses in filial cerebellum. Maternal
      hypothyroxinemia and hypothyroidism models were established in Wistar rats using
      ID diet and deionized water supplemented with different concentrations of
      potassium iodide or MMZ water. Birth weight and cerebellum weight were measured.
      We also examined PF-PC synapses using immunofluorescence, and western blot
      analysis was conducted to investigate the activity of Neurexin1/cerebellin1
      (Cbln1)/glutamate receptor d2 (GluD2) tripartite complex. Our results showed that
      hypothyroxinemia and hypothyroidism decreased birth weight and cerebellum weight
      and reduced the PF-PC synapses on postnatal day (PN) 14 and PN21. Accordingly,
      the mean intensity of vesicular glutamate transporter (VGluT1) and Calbindin
      immunofluorescence was reduced in mild ID, severe ID, and MMZ groups. Moreover,
      maternal hypothyroxinemia and hypothyroidism reduced expression of
      Neurexin1/Cbln1/GluD2 tripartite complex. Our study supports the hypothesis that
      developmental hypothyroxinemia and hypothyroidism reduce PF-PC synapses, which
      may be attributed to the downregulation of Neurexin1/Cbln1/GluD2 tripartite
      complex. 

PMID- 27033233
TI  - Paclitaxel-Coated Balloons: Investigation of Drug Transfer in Healthy and
      Atherosclerotic Arteries - First Experimental Results in Rabbits at Low Inflation
      Pressure.
AB  - PURPOSE: Beyond antiproliferative properties, paclitaxel exhibits anti
      inflammatory activity, which might be beneficial in the local treatment of
      nonocclusive coronary artery disease. Paclitaxel release and tissue
      concentrations after paclitaxel-coated balloon treatment using different
      pressures have not been investigated so far. The aim of the study was to
      investigate in an atherosclerotic rabbit model whether drug transfer from
      paclitaxel-coated balloons into the vessel wall is affected by the presence of
      atherosclerotic lesions and to which extent it depends on the inflation pressure
      used. METHODS: Paclitaxel-coated balloons (3.5 MUg/mm(2) paclitaxel) were
      inflated with pressures of 1, 2, or 6 atm (60s) in healthy (n = 39) and
      atherosclerotic (n = 22) arteries of New Zealand White Rabbits. Paclitaxel
      content in arterial walls (10 min after interventions) and paclitaxel remaining
      on balloons after treatment were analyzed using high-performance liquid
      chromatography. RESULTS: Median paclitaxel tissue concentrations were 829.3 MUg/g
      (IQR 636.5-1487 MUg/g) in healthy and 375.7 MUg/g (IQR 169.8-771.6 MUg/g) in
      atherosclerotic arteries (p = 0.0002). The paclitaxel tissue concentration was
      dependent on inflation pressure (1 atm vs. 2 atm vs. 6 atm) in atherosclerotic
      arteries (p = 0.0106) but not in healthy arteries (p >= 0.05). CONCLUSIONS:
      Atherosclerotic lesions impede the transfer of paclitaxel into arterial walls.
      Higher inflation pressures resulted in an increased paclitaxel transfer in
      atherosclerotic but not in healthy arteries. However, it is assumed that the
      tissue concentrations achieved with an inflation pressure of 2 atm are
      potentially effective in this model.

PMID- 27033234
TI  - Inadequate weight gain in obese women and the risk of small for gestational age
      (SGA): a systematic review and meta-analysis.
AB  - OBJECTIVES: To examine the association between small for gestational age (SGA)
      and inadequate gestational weight gain (GWG) in obese women (compared with
      Institute of Medicine [IOM] guidelines) stratified by obesity classes. METHODS:
      We conducted a meta-analysis of original researches with sufficient information
      about inadequate GWG in obese women stratified by obesity classes. SGA as the
      chief outcome was extracted and assessed in our analysis. MEDLINE and EMBASE were
      searched through Ovid from 28 May 2009 to 1 December 2015. Quality was assessed
      using a modified Newcastle-Ottawa scale. RESULTS: 480 citations were screened and
      13 studies (437 512 obese women) were included. Obese women who gained weight
      below the guidelines had higher risks of SGA than those who gained weight within
      the guidelines (OR 1.28; 95% CI 1.14-1.43). The same conclusions were also
      confirmed in Class I, Class II and Class III of obese women: Class I (OR 1.37;
      95% CI 1.22-1.54); Class II (OR 1.38; 95% CI 1.24-1.54); Class III (OR 1.25; 95%
      CI 1.14-1.36). CONCLUSIONS: From our analysis, the guidelines of IOM can be
      applied to all the classes of obesity. More accurate boundaries for each obesity
      class should be established to evaluate the maternal and fetal risks. Diverse
      populations are thus necessary for more studies in the future.

PMID- 27033235
TI  - On mice and humans: the role of thymic stromal lymphopoietin in human B-cell
      development and leukemia.

PMID- 27033236
TI  - Innovation in hematology: morphology and flow cytometry at the crossroads.

PMID- 27033238
TI  - New and emerging prognostic and predictive genetic biomarkers in B-cell precursor
      acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic
      level. Chromosomal abnormalities are used as diagnostic, prognostic and
      predictive biomarkers to provide subtype, outcome and drug response information.
      t(12;21)/ETV6-RUNX1 and high hyper-diploidy are good-risk prognostic biomarkers
      whereas KMT2A(MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low
      hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1 patients require targeted
      treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes
      when treated intensively. High-risk genetic biomarkers are four times more
      prevalent in adults compared to children. The application of genomic technologies
      to cases without an established abnormality (B-other) reveals copy number
      alterations which can be used either individually or in combination as prognostic
      biomarkers. Transcriptome sequencing studies have identified a network of fusion
      genes involving kinase genes -ABL1,ABL2,PDGFRB,CSF1R,CRLF2,JAK2 and EPOR in-vitro
      and in-vivo studies along with emerging clinical observations indicate that
      patients with a kinase-activating aberration may respond to treatment with small
      molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is
      required to determine the true frequency of these abnormalities across the age
      spectrum and the optimal way to incorporate such inhibitors into protocols. In
      conclusion, genetic biomarkers are playing an increasingly important role in the
      management of patients with ALL.

PMID- 27033237
TI  - Treatment of relapsed and refractory multiple myeloma.
AB  - The approach to the patient with relapsed or relapsed/refractory multiple myeloma
      (RRMM) requires a careful evaluation of the results of previous treatments, the
      toxicities associated with them and an assessment of prognostic factors. Since
      the majority of patients will have received prior therapy with drug combinations
      including a proteasome inhibitor and/or an immunomodulatory drug (IMiD), it is
      the physician's task to choose the right moment for the start of therapy and
      define with the patient which goals need to be achieved. The choice of regimen is
      usually based on prior responsiveness, drugs already received, prior adverse
      effects, the condition of the patient and expected effectiveness and
      tolerability. Many double and triple drug combinations are available. In
      addition, promising new drugs like pomalidomide, carfilzomib and monoclonal
      antibodies are, or will be, available shortly, while other options can be tried
      in clinical studies. Finally, supportive care and palliative options need to be
      considered in some patients. It is becoming increasingly more important to
      consider the therapeutic options for the whole duration of the disease rather
      than take a step by step approach, and to develop a systematic approach for each
      individual patient. 

PMID- 27033239
TI  - Endotoxemia as a trigger of thrombosis in cirrhosis.

PMID- 27033240
TI  - Practical respiratory management in amyotrophic lateral sclerosis: evidence,
      controversies and recent advances.
AB  - In amyotrophic lateral sclerosis, the onset of respiratory muscle weakness is
      silent, but survival following symptom recognition may only be a few weeks.
      Consequently, respiratory function and symptoms should be assessed every 2-3
      months. Noninvasive ventilation improves symptoms, quality of life and survival,
      without increasing carer burden. Lung volume recruitment helps to reverse and
      prevent atelectasis, improving gas exchange, while techniques to enhance sputum
      clearance reduce the risk of mucus plugging and lower respiratory tract
      infections. When noninvasive support fails, often due to severe bulbar
      impairment, tracheostomy ventilation prolongs life. Most patients receiving
      tracheostomy ventilation at home report satisfactory quality of life, but at the
      expense of high carer burden. Diaphragmatic pacing is associated with an
      increased risk of death. 

PMID- 27033241
TI  - Associations of NKX2-5 Genetic Polymorphisms with the Risk of Congenital Heart
      Disease: A Meta-analysis.
AB  - The NKX2-5 gene is a vital regulator of cardiac formation and development.
      Recently, the roles of NKX2-5 63A>G polymorphism and 606G>C polymorphism in
      congenital heart disease (CHD) have been extensively studied, with conflicting
      results. The aim of the present study was to better elucidate the associations
      between NKX2-5 genetic polymorphisms and CHD risk through a meta-analysis.
      Eligible articles were searched in PubMed, MEDLINE, EMBASE, Google Scholar and
      CNKI up to December 2015. Odds ratios (ORs) and 95 % confidence intervals were
      used to detect any potential associations between NKX2-5 genetic polymorphisms
      and CHD risk. Heterogeneity between studies was assessed with Q test and I (2)
      statistic. Subgroup analysis and sensitivity analysis were performed to test the
      reliability and stability of the results, and funnel plots were applied to
      estimate publication bias. A total of 13 case-control studies including 2245 CHD
      patients and 1953 healthy controls were analyzed. The overall meta-analysis
      results showed that NKX2-5 63A>G polymorphism and 606G>C polymorphism were not
      significantly associated with CHD risk. Subgroup analysis was further performed
      for NKX2-5 63A>G polymorphism based on types of CHD and ethnicity of study
      population, and similar negative results were found in all subgroups. Our
      findings suggested that NKX2-5 63A>G polymorphism and 606G>C polymorphism may not
      be implicated in the pathogenesis of CHD. 

PMID- 27033242
TI  - Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.
AB  - Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality
      of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal
      echocardiography. A review of 106 published cases showed that 46 cases with
      prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course
      of cases with prenatally LVHT after publication is unknown, we aimed to collect
      follow-up-information. Information regarding vital status, cardiac and
      extracardiac morbidity was gathered by contacting the authors of the 46 cases.
      Fourteen of the 28 authors answered and gave information about 18 cases (six
      females, seven males, five gender-unknown, age 18 months to 10 years, mean follow
      up 60 months). No differences were found between the 18 cases with follow-up and
      the 28 cases without follow-up regarding age, gender, cardiac or extracardiac
      comorbidities, and interventions. Three of the 18 cases had died subsequently
      from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or
      chromosomal abnormalities were found in six of the seven examined patients,
      extracardiac abnormalities in nine patients. Three patients received a pacemaker
      because of complete AV block, and two patients underwent heart transplantation.
      Cardiac surgical or interventional procedures were carried out in four patients.
      None suffered from malignant arrhythmias or had a cardioverter-defibrillator
      implanted. Based on the limited information, there are indications that cases
      with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if
      they receive appropriate care. Since fetal LVHT is frequently associated with
      genetic abnormalities, further research about survival and underlying genetic
      causes is needed. 

PMID- 27033243
TI  - Complex Chronic Conditions Among Children Undergoing Cardiac Surgery.
AB  - Children with complex chronic conditions (CCCs) require a disproportionate amount
      of inpatient resources and are at increased risk of mortality during hospital
      admissions. This study examines the impact of non-cardiac, comorbid complex
      chronic conditions on outcomes in children undergoing congenital heart surgery.
      All admissions associated with a congenital cardiac surgical procedure in the
      Kids' Inpatient Database from 1997 to 2012 were examined. Children were
      classified by the number as well as type (genetic vs. non-genetic) of CCC.
      Baseline demographics as well as proportion of total inpatient days and total
      hospitalization charges was assessed. Multivariate regression models examining
      occurrence of a complication, mortality, prolonged length of stay and high
      hospitalization charges were constructed. In multivariate models, an increasing
      number of CCC was associated with increased risk of mortality and complications
      (mortality: 1 CCC: odds ratio (OR) = 1.17, 95 % CI = 1.03-1.33); >=2 CCC: OR =
      1.54, 95 % CI = 1.26-1.87). Additionally, the presence of a genetic CCC was
      protective against mortality (OR = 0.71, 95 % CI = 0.56-0.89) while non-genetic
      CCCs were associated with mortality (OR = 1.62, 95 % CI = 1.41-1.88) and high
      resource utilization. Over time, the proportion of genetic CCC remained stable
      while non-genetic CCC increased in prevalence. Complex chronic conditions have a
      varying association with mortality, morbidity and resource utilization in
      children undergoing congenital heart surgery. While genetic CCCs were not
      associated with poor outcomes, non-genetic CCCs were risk factors for morbidity
      and mortality. These findings suggest that pre-surgical counseling and surgical
      planning should account for the type of non-cardiac comorbid conditions. 

PMID- 27033244
TI  - Variation in Antiarrhythmic Management of Infants Hospitalized with
      Supraventricular Tachycardia: A Multi-Institutional Analysis.
AB  - Supraventricular tachycardia (SVT) is the most frequent form of symptomatic
      tachyarrhythmia in infants. The purposes of this study were to describe practice
      patterns of the management of infants hospitalized with SVT and factors
      associated with 30-day hospital readmission. This was a multi-institutional,
      retrospective review of the pediatric health information system database of SVT
      hospitalizations from 2003 to 2013. High-volume centers (HVC) were defined as
      those at the upper quartile of admissions. Infants with an ICD-9 code of
      paroxysmal SVT were included. Antiarrhythmics investigated included amiodarone,
      atenolol, digoxin, esmolol, flecainide, procainamide, propafenone, propranolol,
      and sotalol. Frequency of antiarrhythmic use based on center volume was the
      primary end point. Rate of 30-day SVT readmission was the secondary end point.
      Analysis of factors associated with readmission was assessed by Chi-square
      analysis and expressed as odds ratio and 95 % confidence interval. A total of 851
      patients (60 % male, 44 % neonates) were hospitalized at 43 hospitals.
      Propranolol, digoxin, and amiodarone were the most frequently utilized
      antiarrhythmics. HVCs represented 12 hospitals comprising 494 (58 %) patients.
      Although HVCs were more likely to utilize propranolol (OR 2.5, CI 1.5-4.1), there
      was no significant difference in the 30-day readmission rate between patients
      treated at HVCs versus non-HVCs (p = 0.9). The majority of infants with SVT are
      treated with a small number of antiarrhythmic medications during index
      hospitalization. Although hospital-to-hospital variation in antiarrhythmic choice
      exists, there appears to be no difference in readmission. The remaining practice
      variation may be related to intrinsic patient characteristics. 

PMID- 27033245
TI  - Intervention in Patients with Critical Pulmonary Stenosis in the Ductal Stenting
      Era.
AB  - We aimed to assess early and midterm outcomes of balloon valvuloplasty (BVP)
      procedure in patients with critical pulmonary stenosis (CPS) and to describe the
      predictors of the need for additional pulmonary flow and reintervention in this
      subgroup of patients. From 2005 to 2014, 56 neonates were diagnosed with CPS and
      were included in this study. All echocardiographic, catheterization and
      angiographic data obtained prior to the initial BVP and at follow-up were
      reviewed. BVP was successful in 55 neonates (98 %). Twenty-one neonates needed
      pulmonary blood flow augmentation after BVP (38 %). Ductal stenting (DS) was
      performed in 20. The patients' mean tricuspid valve (TV) annulus diameter was
      10.4 +/- 2 mm, and the Z score was -1.29 +/- 1 (-3.7 to 0.78). The mean pulmonary
      valve (PV) annulus diameter was 6 +/- 0.9 mm, and the Z score was -1.74 +/- 1 (
      4.34 to 0.05). A transcatheter or surgical reintervention was performed in 11
      patients. A TV Z score < -1.93 SD predicted the need for pulmonary blood flow
      augmentation after a successful BVP, with a sensitivity of 63.2% and a
      specificity of 84.4%. A PV Z score < -1.69 SD predicted the need for pulmonary
      flow augmentation, with a sensitivity of 74 %. The presence of bipartite RV was
      found to be a significant predictor of the need for reintervention (odds ratio
      9.6). Our study showed the excellent immediate outcomes of BPV and DS in a pure
      cohort of patients with CPS. Prophylactic DS in selected cases seems reasonable
      and safe. 

PMID- 27033246
TI  - Superior Mesenteric Arterial Flow Pattern is Associated with Major Adverse Events
      in Adults with Fontan Circulation.
AB  - Factors contributing to the failure of Fontan circulation in adults are poorly
      understood. Reduced superior mesenteric arterial (SMA) flow has been identified
      in pediatric Fontan patients with protein-losing enteropathy. SMA flow has not
      been profiled in an adult Fontan population and its association with adverse
      events is unknown. We aimed to examine associations between SMA flow patterns and
      adverse events in adult Fontan patients. We performed a retrospective review of
      adult Fontan patients who underwent echocardiograms between 2008 and 2014. SMA
      Doppler data included peak systolic and end-diastolic velocity and velocity time
      integral (VTI). Systolic/diastolic (S/D) ratio and resistive index were
      calculated. The relationship between SMA flow parameters and major adverse events
      (death or transplantation) was examined using proportional hazard Cox regression
      analyses. Kaplan-Meyer analysis was conducted to construct survival curve of
      patients with and without adverse events. 91 post-Fontan adult patients (76 %
      systemic left ventricle, 20 % atriopulmonary Fontan, mean age 27.9 years) were
      analyzed. Adverse events occurred in nine patients (death = 4, transplant = 5).
      When compared with the non-event group, the event group had increased end
      diastolic velocity [hazard ratio (HR) 1.5, 95 % confidence interval (CI) 1.1-1.8;
      p = 0.002], increased systolic VTI (HR 1.5, 95 % CI 1.1-2.2, p = 0.02), increased
      diastolic VTI (HR 1.7, 95 % CI 1.2-2.4, p = 0.004), decreased S/D velocity ratio
      (HR 0.32, 95 % CI 0.14-0.71, p = 0.006), decreased S/D VTI ratio (HR 0.76, 95 %
      CI 0.61-0.97, p = 0.02), and decreased resistive index (HR 0.29, 95 % CI 0.14
      0.60, p = 0.0007). Increased end-diastolic velocity and VTI in mesenteric
      arterial flow, with lower systolic/diastolic ratio and resistive index, were
      associated with death and need for heart transplant in adult Fontan patients. The
      mesenteric hyperemic flow was also associated with clinical signs of portal
      venous outflow obstruction, suggesting the presence of vasodilatory state in end
      stage adult Fontan circulation. 

PMID- 27033248
TI  - Conducting LaAlO3/SrTiO3 heterointerfaces on atomically-flat substrates prepared
      by deionized-water.
AB  - We have investigated how the recently-developed water-leaching method for
      atomically-flat SrTiO3 (STO) substrates affects the transport properties of
      LaAlO3 (LAO) and STO heterointerfaces. Using pulsed laser deposition at identical
      growth conditions, we have synthesized epitaxial LAO thin-films on two different
      STO substrates, which are prepared by water-leaching and buffered hydrofluoric
      acid (BHF) etching methods. The structural, transport, and optical properties of
      LAO/STO heterostructures grown on water-leached substrates show the same high
      quality as the samples grown on BHF-etched substrates. These results indicate
      that the water-leaching method can be used to grow complex oxide heterostructures
      with atomically well-defined heterointerfaces without safety concerns. 

PMID- 27033247
TI  - The Prevalence of Left Ventricular Hypertrophy in Obese Children Varies Depending
      on the Method Utilized to Determine Left Ventricular Mass.
AB  - Obesity and left ventricular hypertrophy (LVH) have been identified as
      independent risk factors for cardiovascular events. The definition of LVH depends
      on the geometric algorithm used to calculate LV mass (LVM) by echocardiography
      and the method used to normalize LVM for body size. This study evaluates the
      effect of these methods on the prevalence of LVH in obese children. LVM for 109
      obese and 109 age-matched non-obese children was calculated using M-mode or two
      dimensional echocardiography (2DE). LVM was then normalized to height 2.7 as
      indexed LVM (LVMI), to body surface area (BSA), height, and lean body mass (LBM)
      as LVM Z-scores. LVH was defined as LVMI >95th 0/00 using age-specific normal
      reference values or LVM Z-scores >=2. The prevalence of LVH by LVMI and LVM Z
      scores was compared. There was a correlation between LVM determined by M-mode and
      by 2DE (R (2) = 0.91), although M-mode LVM was greater than 2DE LVM. However, the
      difference between these values was greater in obese children than in non-obese
      children. Based on the method of normalization, the prevalence of LVH among obese
      children was 64 % using LVMI, 15 % using LVM Z-scores for height, 8 % using LVM Z
      scores for BSA and 1 % using LVM Z-scores for LBM. Height-based normalization
      correlates with obesity and hypertension. The methods used to measure and
      normalize LVM have a profound influence on the diagnosis of LVH in obese
      children. Further study is needed to determine which method identifies children
      at risk for cardiovascular morbidity and mortality. 

PMID- 27033249
TI  - Efficient and stable perovskite solar cells prepared in ambient air irrespective
      of the humidity.
AB  - Poor stability of organic-inorganic halide perovskite materials in humid
      condition has hindered the success of perovskite solar cells in real applications
      since controlled atmosphere is required for device fabrication and operation, and
      there is a lack of effective solutions to this problem until now. Here we report
      the use of lead (II) thiocyanate (Pb(SCN)2) precursor in preparing perovskite
      solar cells in ambient air. High-quality CH3NH3PbI3-x(SCN)x perovskite films can
      be readily prepared even when the relative humidity exceeds 70%. Under optimized
      processing conditions, we obtain devices with an average power conversion
      efficiency of 13.49% and the maximum efficiency over 15%. In comparison with
      typical CH3NH3PbI3-based devices, these solar cells without encapsulation show
      greatly improved stability in humid air, which is attributed to the incorporation
      of thiocyanate ions in the crystal lattice. The findings pave a way for realizing
      efficient and stable perovskite solar cells in ambient atmosphere. 

PMID- 27033250
TI  - The question should be whether the timing of vaccination optimises the impact on
      child health.

PMID- 27033252
TI  - Systematic review in The BMJ leads to changes to Australian guidelines on
      hydrolysed formula.

PMID- 27033251
TI  - Therapeutic hypothermia protects against ischemia-induced impairment of synaptic
      plasticity following juvenile cardiac arrest in sex-dependent manner.
AB  - Pediatric cardiac arrest (CA) often leads to poor neurologic outcomes, including
      deficits in learning and memory. The only approved treatment for CA is
      therapeutic hypothermia, although its utility in the pediatric population remains
      unclear. This study analyzed the effect of mild therapeutic hypothermia after CA
      in juvenile mice on hippocampal neuronal injury and the cellular model of
      learning and memory, termed long-term potentiation (LTP). Juvenile mice were
      subjected to cardiac arrest and cardiopulmonary resuscitation (CA/CPR) followed
      by normothermia (37 degrees C) and hypothermia (30 degrees C, 32 degrees C).
      Histological injury of hippocampal CA1 neurons was performed 3days after
      resuscitation using hematoxylin and eosin (H&E) staining. Field excitatory post
      synaptic potentials (fEPSPs) were recorded from acute hippocampal slices 7days
      after CA/CPR to determine LTP. Synaptic function was impaired 7days after CA/CPR.
      Mice exposed to hypothermia showed equivalent neuroprotection, but exhibited
      sexually dimorphic protection against ischemia-induced impairment of LTP.
      Hypothermia (32 degrees C) protects synaptic plasticity more effectively in
      females, with males requiring a deeper level of hypothermia (30 degrees C) for
      equivalent protection. In conclusion, male and female juvenile mice exhibit
      equivalent neuronal injury following CA/CPR and hypothermia protects both males
      and females. We made the surprising finding that juvenile mice have a sexually
      dimorphic response to mild therapeutic hypothermia protection of synaptic
      function, where males may need a deeper level of hypothermia for equivalent
      synaptic protection.

PMID- 27033253
TI  - Cancer stem cell marker expression alone and in combination with microvascular
      invasion predicts poor prognosis in patients undergoing transplantation for
      hepatocellular carcinoma.
AB  - BACKGROUND: The cancer stem cell hypothesis provides an explanation for
      hepatocellular carcinoma (HCC) heterogeneity. We investigated the expression of
      CD44 and CD133 alone and in combination with microvascular invasion (MVI) as
      predictors of prognosis in patients undergoing liver transplantation for HCC.
      METHODS: Explanted livers from 95 patients transplanted for HCC were analyzed.
      Marker expression was evaluated by immunofluorescence. RESULTS: Seventy-seven
      patients were male with a mean age of 56 years. The most common etiologies of
      cirrhosis were hepatitis C (50%) and alcoholic liver disease (41%). Forty-one
      patients had laboratory model for end-stage liver disease score greater than 15.
      Overall survival (OS) at 1-, 3-, and 5-years was 86%, 75%, and 64%, respectively.
      Recurrence rate was 13% with a median follow-up of 64 months. The 5-year OS was
      significantly lower in those patients with MVI and CD44 (36.9%) or CD133 (40%).
      CD44(+) and CD133(+) correlated with increased risk of poorly differentiated HCC,
      and elevated alpha-fetoprotein levels. In combination with MVI, both markers were
      independently associated with increased recurrence and worse OS (recurrence P <
      .003, odds ratio = 8.05; P = .001, odds ratio = 9.5, survival P = .001, HR = 3.7;
      P = .004, HR = 3.2 respectively). CONCLUSIONS: CD44 or CD133 alone and in
      combination with MVI are independent predictors of poor prognosis in patients
      undergoing transplantation for HCC.

PMID- 27033254
TI  - Local resection for duodenal gastrointestinal stromal tumors.
AB  - BACKGROUND: Duodenal gastrointestinal tumors (GIST) present infrequently, and
      surgical resection with negative margins remains the mainstay of therapy;
      however, given the lack of lymphatic and submucosal spread and anatomic location
      near the bile duct and pancreas, the optimal approach for resection is unknown.
      Options include local resection (LR), segmental resection, and
      pancreaticoduodenectomy (PD). METHODS: All cases of gastrointestinal stromal
      tumors originating from the duodenum from 2000 to 2015 were identified from
      administrative databases. Clinical and pathologic information was abstracted from
      the medical record and compared between patients who received LR vs PD. The chi
      square with Fisher's exact test was used to detect differences between groups.
      RESULTS: Fifteen patients met the inclusion criteria, of which 7 had an LR and 8
      had a PD. The second portion of the duodenum was the most common origin of GIST
      in the PD group, whereas the third portion was most common in the LR group.
      Patients who underwent LR tended to be younger, but there was no difference in
      tumor size, mitotic rate, margin positivity, readmission rate, or recurrence. PD
      was associated with more complications, higher blood loss, and longer length of
      stay. CONCLUSIONS: Local resection is a reasonable option for resection of
      duodenal GIST and should be routinely considered if technically feasible.

PMID- 27033255
TI  - CLEC5A is critical for dengue virus-induced osteoclast activation and bone
      homeostasis.
AB  - Osteoclasts are bone tissue macrophages critical to maintain bone homeostasis.
      However, whether osteoclasts are susceptible to flaviviral infections and
      involved in dengue virus (DV)-induced disease pathogenesis is still unknown. In
      this study, we found that osteoclasts were preferentially susceptible to DV
      infection and produced similar amounts of cytokines and infectious virions as
      macrophages. Interestingly, DV-induced cytokine secretion and nuclear
      translocation of the transcription factor NFATc1 in osteoclast via the Syk
      coupled myeloid C-type lectin member 5A (CLEC5A). Moreover, DV caused transient
      inflammatory reaction in bone tissue and upregulated osteolytic activity to
      release C-telopeptide of type I collagen (CTX-1) from bone tissue. Furthermore,
      DV-induced osteolytic activity was attenuated in CLEC5A-deficient mice, and
      administration of antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic
      activity and reduced CTX-1 serum level in vivo. This observation suggests that
      osteoclasts serve as a novel target for DV, and transient upregulation of
      osteolytic activity may contribute to the clinical symptoms in dengue patients.
      KEY MESSAGES: Cultured osteoclasts were susceptible to DV infection. Osteoclasts
      produced similar amounts of cytokines and infectious virions as macrophages. DV
      induced nuclear translocation of NFATc1 in osteoclast via CLEC5A. DV caused
      transient inflammatory reaction in bone tissue and upregulated osteolytic
      activity. Antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity
      in vivo.

PMID- 27033258
TI  - Beadle and Tatum and the origins of molecular biology.

PMID- 27033259
TI  - Editorial comment on 'Effects of neoadjuvant chemotherapy with or without
      zoledronic acid on pathological response: A meta-analysis of randomised trials'.

PMID- 27033256
TI  - Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases.
AB  - The roles of cyclins and their catalytic partners, the cyclin-dependent kinases
      (CDKs), as core components of the machinery that drives cell cycle progression
      are well established. Increasing evidence indicates that mammalian cyclins and
      CDKs also carry out important functions in other cellular processes, such as
      transcription, DNA damage repair, control of cell death, differentiation, the
      immune response and metabolism. Some of these non-canonical functions are
      performed by cyclins or CDKs, independently of their respective cell cycle
      partners, suggesting that there was a substantial divergence in the functions of
      these proteins during evolution.

PMID- 27033260
TI  - Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal
      stromal tumour - Does it increase the risk for tumour cell seeding and
      recurrence?
AB  - PURPOSE: Preoperative percutaneous transabdominal wall biopsy may be considered
      to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative
      treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not
      possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding
      and conversion of a local GIST to a disseminated one. We investigated the
      influence of preoperative needle biopsy on survival outcomes. METHODS: We
      collected the clinical data from hospital case records of the 397 patients who
      participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft
      Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine
      needle and/or core needle biopsy carried out prior to study entry. The SSG
      XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient
      population with a high risk of GIST recurrence after macroscopically radical
      surgery. The primary end-point was recurrence-free survival (RFS), and the
      secondary end-points included overall survival (OS). RESULTS: A total of 47
      (12.0%) out of the 393 patients with data available underwent a percutaneous
      biopsy. No significant difference in RFS or OS was found between the patients who
      underwent or did not undergo a percutaneous biopsy either in the entire series or
      in subpopulation analyses, except for a statistically significant RFS advantage
      for patients who had a percutaneous biopsy and a tumour >=10 cm in diameter.
      CONCLUSION: A preoperative diagnostic percutaneous biopsy of a suspected GIST may
      not increase the risk for GIST recurrence in a patient population who receive
      adjuvant imatinib after the biopsy.

PMID- 27033257
TI  - VRACs and other ion channels and transporters in the regulation of cell volume
      and beyond.
AB  - Cells need to regulate their volume to counteract osmotic swelling or shrinkage,
      as well as during cell division, growth, migration and cell death. Mammalian
      cells adjust their volume by transporting potassium, sodium, chloride and small
      organic osmolytes using plasma membrane channels and transporters. This generates
      osmotic gradients, which drive water in and out of cells. Key players in this
      process are volume-regulated anion channels (VRACs), the composition of which has
      recently been identified and shown to encompass LRRC8 heteromers. VRACs also
      transport metabolites and drugs and function in extracellular signal
      transduction, apoptosis and anticancer drug resistance.

PMID- 27033261
TI  - Variation in the HFE gene is associated with the development of bleomycin-induced
      pulmonary toxicity in testicular cancer patients.
AB  - BACKGROUND: Bleomycin and cisplatin are of key importance in testicular cancer
      treatment. Known potential serious adverse effects are bleomycin-induced
      pulmonary toxicity (BIP) and cisplatin-induced renal toxicity. Iron handling may
      play a role in development of this toxicity. Carriage of allelic variants of the
      HFE gene induces altered iron metabolism and may contribute to toxicity. We
      investigated the association between two common allelic variants of the HFE gene,
      H63D and C282Y, with development of pulmonary and renal toxicity during and after
      treatment with bleomycin- and cisplatin-containing chemotherapy. METHODS: In 369
      testicular cancer patients treated with bleomycin and cisplatin at the University
      Medical Center Groningen between 1978 and 2006, H63D and/or C282Y genotypes were
      determined with an allelic discrimination assay. Data were collected on
      development of BIP, pulmonary function parameters, renal function, and survival.
      RESULTS: BIP developed more frequently in patients who were heterozygote (16 in
      75, 21%) and homozygote (2 in 4, 50%) for the H63D variant, compared with those
      who had the HFE wild-type gene (31 in 278, 11%) (p = 0.012). Overall survival,
      testicular cancer-related survival, and change in renal function were not
      associated with the H63D variant. CONCLUSION: We observed an association between
      presence of one or both H63D alleles and development of BIP in testicular cancer
      patients treated with bleomycin combination chemotherapy. In patients
      heterozygote and homozygote for the H63D variant, BIP occurred more frequently
      compared with wild-type patients. When validated and confirmed, HFE H63D
      genotyping may be used to identify patients with increased risk for pulmonary
      bleomycin toxicity.

PMID- 27033263
TI  - How to improve the outcome of patients with traumatic brain injury in China.

PMID- 27033262
TI  - Maternal exercise during pregnancy promotes physical activity in adult offspring.
AB  - Previous rodent studies have shown that maternal voluntary exercise during
      pregnancy leads to metabolic changes in adult offspring. We set out to test
      whether maternal voluntary exercise during pregnancy also induces persistent
      changes in voluntary physical activity in the offspring. Adult C57BL/6J female
      mice were randomly assigned to be caged with an unlocked (U) or locked (L)
      running wheel before and during pregnancy. Maternal running behavior was
      monitored during pregnancy, and body weight, body composition, food intake,
      energy expenditure, total cage activity, and running wheel activity were measured
      in the offspring at various ages. U offspring were slightly heavier at birth, but
      no group differences in body weight or composition were observed at later ages
      (when mice were caged without access to running wheels). Consistent with our
      hypothesis, U offspring were more physically active as adults. This effect was
      observed earlier in female offspring (at sexual maturation). Remarkably, at 300 d
      of age, U females achieved greater fat loss in response to a 3-wk voluntary
      exercise program. Our findings show for the first time that maternal physical
      activity during pregnancy affects the offspring's lifelong propensity for
      physical activity and may have important implications for combating the worldwide
      epidemic of physical inactivity and obesity.-Eclarinal, J. D., Zhu, S., Baker, M.
      S., Piyarathna, D. B., Coarfa, C., Fiorotto, M. L., Waterland, R. A. Maternal
      exercise during pregnancy promotes physical activity in adult offspring.

PMID- 27033264
TI  - Traumatic brain injury: Changing concepts and approaches.
AB  - Traumatic brain injury (TBI) represents a huge global medical and public health
      problem across all ages and in all populations. In this review, we discussed the
      changing concepts and approaches. Globally, the incidence is increasing and in
      high income countries epidemiologic patterns are changing with consequences for
      prevention campaigns. TBI should not be viewed as an event, but as a progressive
      and chronic disease with lifetime consequences. In the clinical field, precision
      approaches to treatment are being developed, which require more accurate disease
      phenotyping. Recent advances in genomics, neuroimaging and biomarker development
      offer great opportunities to develop improved phenotyping and better disease
      characterization. In clinical research, randomized controlled clinical trials are
      being complemented by large data collections in broad TBI populations in
      comparative effectiveness designs. Global collaborations are being developed
      among funding agencies, research organizations and researchers. Only by combining
      efforts and collaboration will we be able to advance the field by providing long
      needed evidence to support practice recommendations and to improve treatment. 

PMID- 27033265
TI  - Anatomy and physiology of cisternostomy.
AB  - Cisternostomy is defined as opening the basal cisterns to atmospheric pressure.
      This technique helps to reduce the intracranial pressure in severe head trauma as
      well as other conditions when the so-called sudden "brain swelling" troubles the
      surgeon. We elaborated the surgical anatomy of this procedure as well as the
      proposed physiology of how cisternostomy works. This novel technique may change
      the current trends in neurosurgery. 

PMID- 27033266
TI  - Alteration of microRNA expression in cerebrospinal fluid of unconscious patients
      after traumatic brain injury and a bioinformatic analysis of related single
      nucleotide polymorphisms.
AB  - PURPOSE: It is becoming increasingly clear that genetic factors play a role in
      traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or
      determining susceptibility to it. MicroRNAs are small RNA molecules involved in
      various pathophysiological processes by repressing target genes at the post-
      transcriptional level, and TBI alters microRNA expression levels in the
      hippocampus and cortex. This study was designed to detect differentially
      expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining
      unconscious two weeks after initial injury and to explore related single
      nucleotide polymorphisms (SNPs). METHODS: We used a microarray platform to detect
      differential microRNA expression levels in CSF samples from patients with post
      traumatic coma compared with samples from controls. A bioinformatic scan was
      performed covering microRNA gene promoter regions to identify potential
      functional SNPs. RESULTS: Totally 26 coma patients and 21 controls were included
      in this study, with similar distribution of age and gender between the two
      groups. Microarray showed that fourteen microRNAs were differentially expressed,
      ten at higher and four at lower expression levels in CSF of traumatic coma
      patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was
      identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region.
      CONCLUSION: The altered microRNA expression levels in CSF after brain injury
      together with SNP identified within the microRNA gene promoter area provide a new
      perspective on the mechanism of impaired consciousness after TBI. Further studies
      are needed to explore the association between the specific microRNAs and their
      related SNPs with post-traumatic unconsciousness.

PMID- 27033267
TI  - Improved neurite outgrowth on central nervous system myelin substrate by siRNA
      mediated knockdown of Nogo receptor.
AB  - PURPOSE: To investigate the in vitro effect of short interfering RNAs (siRNAs)
      against Nogo receptor (NgR) on neurite outgrowth under an inhibitory substrate of
      central nervous system (CNS) myelin. METHODS: Three siRNA sequences against NgR
      were designed and transfected into cerebellar granule cells (CGCs) to screen for
      the most effcient sequence of NgR siRNA by using reverse transcription polymerase
      chain reaction (RT-PCR) and immunofluorescence staining. NgR siRNA sequence 1 was
      found the most efficient which was then transfected into the CGCs grown on CNS
      myelin substrate to observe its disinhibition for neurite outgrowth. RESULTS:
      Compared with the scrambled control sequence of siRNA, the NgR siRNA sequence 1
      significantly decreased NgR mRNA level at 24 h and 48 h (p <0.05), which was
      recovered by 96 h after transfection. NgR immunoreactivity was also markedly
      reduced at 24 and 48 h after the transfection of siRNA sequence 1 compared with
      that before transfection (p<0.05). The NgR immunoreactivity was recovered after
      72 h post-transfection. Moreover, the neurite outgrowth on the myelin substrate
      was greatly improved within 72 h after the transfection with siRNA sequence 1
      compared with the scrambled sequence-transfected group or non-transfected group
      (p<0.05). CONCLUSION: siRNA-mediated knockdown of NgR expression contributes to
      neurite outgrowth in vitro.

PMID- 27033268
TI  - A comparative study between Marshall and Rotterdam CT scores in predicting early
      deaths in patients with traumatic brain injury in a major tertiary care hospital
      in Nepal.
AB  - PURPOSE: CT plays a crucial role in the early assessment of patients with
      traumatic brain injury (TBI). Marshall and Rotterdam are the mostly used scoring
      systems, in which CT findings are grouped differently. We sought to determine the
      values of the scoring system and initial CT findings in predicting the death at
      hospital discharge (early death) in patients with TBI. METHODS: There were
      consecutive 634 traumatic neurosurgical patients with mild-to-severe TBI admitted
      to the emergency department of College of Medical Sciences. Their initial CT and
      status at hospital discharge (dead or alive) were reviewed, and both CT scores
      were calculated. We examined whether each score is related to early death;
      compared the two scoring systems' performance in predicting early death, and
      identified the CT findings that are independent predictors for early death.
      RESULTS: Both imaging score (Marshall) and clinical score (Rotterdam) can be used
      to reliably predict mortality in patients with acute traumatic brain injury with
      high prognostic accuracy. Other specific CT characteristics that can be used to
      predict early mortality are traumatic subarachnoid hemorrhage, midline shift and
      status of the peri-mesencephalic cisterns. CONCLUSIONS: Marshall CT
      classification has strong predictive power, but greater discrimination can be
      obtained if the individual CT parameters underlying the CT classification are
      included in a prognostic model as in Rotterdam score. Consequently, for
      prognostic purposes, we recommend the use of individual characteristics rather
      than the CT classification. Performance of CT models for predicting outcome in
      TBI can be significantly improved by including more details of variables and by
      adding other variables to the models.

PMID- 27033269
TI  - Aspiration of coagulated hematoma in the third and fourth ventricles via paracele
      anterior horn puncture.
AB  - Intraventricular hemorrhage (IVH) is a neurological urgency with a high mortality
      and unfavorable prognosis. Fast removal of intraventricular blood should be
      considered as a priority. The current treatments of IVH mainly focus on external
      ventricular drain and endoscopic aspiration, but neither way can remove the blood
      in the fourth ventricle easily and relieve the compression of brainstem. Here we
      report a unique procedure to solve this problem. A 41-year-old male patient who
      had suffered sudden attack of headache and disturbance of consciousness for 2 h
      was diagnosed as having high density lesion in the whole ventricular system by
      computed tomographic (CT) imaging. An emergent bilateral ventriculopuncture and
      intraventricular hematoma removal under non-line-of-sight was performed
      immediately; the catheter was extended to the fourth ventricle to maximally
      remove the hematoma. Postoperative CT scan demonstrated total removal of IVH and
      no sign of extra brain damage. 

PMID- 27033270
TI  - Clinical application of three-dimensional printing in the personalized treatment
      of complex spinal disorders.
AB  - PURPOSE: To investigate the usefulness of three-dimensional (3D) printing in
      complex spinal surgery. METHODS: The study was conducted from October 2014 to
      March 2015 in Shenzhen Second Peoples' Hospital and 4 cases of complex severe
      spinal disorders were selected from our department. Among them one patient
      combined with congenital scoliosis, one with atlas neoplasm, one with
      atlantoaxial dislocation, and the rest one with atlantoaxial fracture
      dislocation. The data of the diseased region was collected from computerized
      tomography scans for 3D digital reconstruction and rapid prototyping to prepare
      photosensitive resin models, which were applied in the treatment of these cases.
      RESULTS: The use of 3D models reduced operating time and intraoperative blood
      loss as well as the risk of postoperative complications. Furthermore, no pedicle
      penetrations or screw misplacement occurred according to the postoperative planar
      radiographic images. CONCLUSION: The tactile models from 3D printing allow direct
      observation and measurement, helping the orthopedists to have accurate
      morphometric information to provide personalized surgical planning and better
      communication with the patient and coworkers. Moreover, the photosensitive resin
      models can also guide the actual surgery with the drilling of pedicle screws and
      safe resection of tumor.

PMID- 27033271
TI  - Subfascial drainage for management of cerebrospinal fluid leakage after posterior
      spine surgeryd---A prospective study based on Poiseuille's law.
AB  - PURPOSE: Up to date, some approaches retarding the flow of cerebrospinal fluid
      (CSF) could be regarded as direct applications of the fluid mechanics
      (Poiseuille's law). However, there is a lack of the research on the efficacy of
      subfascial drainage for management of CSF leak after spine surgery based on the
      law. This is a prospective and comparative study on subfascial drainage for CSF.
      METHODS: Every four months in the three years from January 2010 to December 2012,
      the patients were enrolled respectively in Group A, Group B and Group C, in
      which, the drainage tube was discontinued within postoperative 3-4 days, 5-6
      days, 7-10 days. Results and complications of postoperative CSF leak were
      investigated, and mean wound healing time (MWHT) of the three groups was
      compared. RESULTS: A total of 108 cases (Group A/B/C:35/32/41) of CSF leak
      following posterior spine surgery were admitted to Tianjin Union Medicine Center,
      and 92 cases have been followed up for more than 1 year (follow-up rate of
      85.2%). Preoperative demographics were similar among the 3 groups. In Group A, 7
      patients developed CSF leak through the wound (CSFLW), of which 5 cases had to
      undergo reoperation. One case in Group A was confirmed to have pseudomeningocele
      at the 1st month after surgery. The MWHT was (16.6+/-3.6) days. In Group B, 3
      patients developed CSFLWand cured by reoperation, in which 1 case of superficial
      infection recovered well after reoperation. MWHT was (11.4+/-2.2) days. In Group
      C, CSFLWwas not found and MWHT was (10.1+/-2.9) days. The differences of MWHT
      among Groups A, B and C were statistically significant. CONCLUSION: Postoperative
      subfascial drainage, which is used to decrease the subfascial space pressure
      (P2), would help wound healing. When it is placed for more than 7 days, the wound
      resistance (Rw) would be strong enough to withstand the subarachnoid pressure
      (P1). Meanwhile, the power trans- duction in a sequence of Rw > P2 > P1 will
      indirectly retard CSF leak at the durotomy site and accordingly facilitate the
      healing of damaged spinal dura mater.

PMID- 27033272
TI  - Minimally invasive osteosynthesis of distal tibial fractures using anterolateral
      locking plate: Evaluation of results and complications.
AB  - PURPOSE: Soft tissue healing is of paramount importance in distal tibial
      fractures for a successful outcome. There is an increasing trend of using
      anterolateral plate due to an adequate soft tissue cover on ante- rolateral
      distal tibia. The aim of this study was to evaluate the results and complications
      of minimally invasive anterolateral locking plate in distal tibial fractures.
      METHODS: This is a retrospective study of 42 patients with distal tibial
      fractures treated with minimally invasive anterolateral tibial plating. This
      study evaluates the bone and soft tissue healing along with emphasis on
      complications related to bone and soft tissue healing. RESULTS: Full weight
      bearing was allowed in mean time period of 4.95 months (3-12 months). A major
      local complication of a wound which required revision surgery was seen in one
      case. Minor complications were identified in 9 cases which comprised 4 cases of
      marginal necrosis of the surgical wound, 1 case of superficial infection, 1 case
      of sensory disturbance over the anterolateral foot, 1 case of muscle hernia and 2
      cases of delayed union. Mean distance between the posterolateral and
      anterolateral incision was 5.7 cm (4.5-8 cm). CONCLUSION: The minimally invasive
      distal tibial fixation with anterolateral plating is a safe method of
      stabilization. Distance between anterolateral and posterolateral incision can be
      placed less than 7 cm apart depending on fracture pattern with proper surgical
      timing and technique.

PMID- 27033273
TI  - Bedside ultrasonography for verification of shoulder reduction: A long way to go.
AB  - PURPOSE: Shoulder dislocation is a common joint dislocation managed by the
      emergency physicians in the emergency departments. Pre- and post-reduction
      radiographic examinations have long been the standard practice to confirm the
      presence of dislocation and the successful reduction. However, shoulder
      ultrasonography has recently been proposed as an alternative to the radiographic
      examination. This study aimed to assess the accuracy of ultrasonography in
      evaluating proper reduction of the dislocated joint. METHODS: This was a
      prospective observational study. All patients with confirmed anterior shoulder
      dislocation were examined by both ultrasonography and radiography after the
      attempt for reduction of the dislocated joint. The examiners were blinded to the
      result of the other imaging modality. Results of the two methods were then
      compared. RESULTS: Overall, 108 patients with confirmed anterior shoulder
      dislocation were enrolled in the study. Ninety-one (84.3%) of the patients were
      males. Mean age of the participants was (30.11 +/- 11.41) years. The majority of
      the patients had a recurrent dislocation. Bedside ultrasonography showed a
      sensitivity of 53.8% (95% CI: 29.1%-76.8%) and a specificity of 100% (95% CI:
      96.1%-100%) in detecting inadequate reductions. The results of ultrasonography
      had a statistically significant agreement with the results of radiography (Kappa
      = 0.672, p < 0.001). CONCLUSION: The results suggest that the sensitivity of post
      reduction ultrasound is not sufficient for it to serve as a substitute for
      radiography.

PMID- 27033274
TI  - The instability of wrist joint and total wrist replacement.
AB  - Total wrist arthroplasty are not used as widely as total knee and hip
      replacement. The functional hands are requiring surgeons to design a durable and
      functional satisfying prosthesis. This article will list the main reasons that
      cause the failure of the prosthesis. Some remarkable and representative
      prostheses are listed to show the devolvement of total wrist prosthesis and their
      individual special innovations to fix the problems. And the second part we will
      discuss the part that biomechanical elements act in the total wrist replacement
      (TWA). Summarize and find out what the real problem is and how we can find a way
      to fix it. 

PMID- 27033275
TI  - Treatment of thoracic hemorrhage due to rupture of traumatic mediastinal
      hematoma.
AB  - Patients in traffic accidents are usually presented with pain and bleeding due to
      fractures or soft tissue injury. On some occasions, more severe complications may
      be triggered by the trauma. A review of the published English language literature
      reveals no survival case once the traumatic mediastinal hematoma is ruptured. In
      our case, a 54-year-old man suffering motorcycle accident was admitted to
      emergency department. Computed tomography scan revealed subdural hematoma
      combined with posterior mediastinal hematoma. The patient was saved and
      discharged with a satisfactory outcome. Here we hope to share our treatment
      experience in dealing with the patient with severe multiple trauma. 

PMID- 27033276
TI  - Uncontrolled haemorrhage in pelvic fracturesd---Can the inevitable be avoided?
AB  - Pelvic fractures carry a considerable risk for morbidity and mortality. Half or
      more of the early deaths in these patients have been attributed directly to
      haemorrhage. The transfusional requirements are four times higher for open pelvic
      fractures compared with a similar group of closed pelvic fractures. The loss of
      the tamponade effect by disruption of the pelvic soft tissues and the energy
      imparted play a central role in this potentially life threatening situation. We
      reported a case of open pelvic fracture in which persistent haemorrhage was
      stopped by giving recombinant activated coagulation factor VIIa as our last
      resort. 

PMID- 27033277
TI  - Brachymetatarsia with accessory navicular in right foot: A rare coincidental
      finding.
AB  - A 33 years old female patient presented with posttraumatic pain in the right foot
      for which radiographs of the right foot was advised. No fracture was detected on
      radiographs and patient was managed conservatively on medications and posterior
      splint immobilization. We found coincidentally a short fourth metatarsal and an
      accessory navicular bone in the right foot radiographs. After 3 weeks of
      immobilization, she underwent mobilization of the right foot, weight bearing and
      intensive physio- therapy for 6 weeks. After two months of injury she was still
      complaining of pain on the plantar aspect of right foot which was diagnosed as
      metatarsalgia and operated on by excision of the neuroma present in the 3rd web
      space of the right foot. After surgery she was completely relieved of pain and
      could do activities well related to the right foot. 

PMID- 27033278
TI  - Simultaneous bilateral shoulder and bilateral central acetabular fracture
      dislocation: What to do?
AB  - Musculoskeletal injuries following seizures have a high morbidity and mortality.
      These injuries are often missed and the diagnosis is delayed due to a lack of
      clinical suspicion and appropriate investigations.We report a case of 72 years
      old male with simultaneous bilateral central acetabular fracture dislocation and
      bilateral posterior shoulder fracture dislocation secondary to an epileptic
      seizure. Present study high- lights the significance of clinical suspicion and
      clinico-radiological evaluation for diagnosis of a rare injury following episode
      of seizures. Simultaneous fracture dislocation of all four limbs treated with a
      holistic approach can lead to a good functional recovery. Surgical management
      with open reduction and internal fixation is preferred and replacement
      arthroplasty should be reserved for cases with implant failure and elderly
      patients. 

PMID- 27033279
TI  - Nasal septal perforation in the course of anti-MDA5 dermatomyositis.

PMID- 27033280
TI  - A neoteric multidrug combination: novel approach to limited cutaneous systemic
      scleroderma involving the face.
AB  - Limited cutaneous scleroderma is a subtype of scleroderma limited to the skin of
      the face, hands, feet and forearms. We present a case of a 45-year-old woman
      affected by limited cutaneous systemic scleroderma involving the orofacial region
      and causing restricted mouth opening. The patient showed noteworthy improvement
      of the skin lesion by use of a combination of intralesional corticosteroid with
      hyaluronidase and various multiantioxidants, resulting in amelioration of her
      mouth opening problem. The patient gave her full informed written consent to this
      report being published. 

PMID- 27033281
TI  - Perivascular parenchymal extension of the ablation zone following liver microwave
      ablation.
AB  - A 69-year-old man who presented with abdominal discomfort was, on examination,
      found to have a palpable abdominal mass. Contrast-enhanced CT showed a mass
      arising from the inferior vena cava, which biopsy confirmed to be a
      leiomyosarcoma. One month after chemoradiotherapy, CT demonstrated a new 15 mm
      solitary central right liver metastasis. Microwave ablation (MWA) of the
      metastasis was performed using an Acculis Sulis V system (Angiodynamics, USA) at
      a power of 140 Watts for 4 min, with no immediate complications. After 1 month,
      MRI with gadolinium was performed to assess the liver ablation zone. The MRI
      demonstrated thrombosis of a right inferior hepatic vein branch leading to the
      ablation zone and extension of the ablation zone 1 cm into the tissue around the
      thrombosed vessel.

PMID- 27033282
TI  - Pilocytic astrocytoma.

PMID- 27033283
TI  - Unusual aetiology of abdominal wall abscess: cholecystocutaneous fistula
      presenting 20 years after open subtotal cholecystectomy.
AB  - A 68-year-old woman presented to the emergency department, with an abscess in the
      right upper anterior abdominal wall. She had a medical history of an open
      cholecystectomy 20 years prior, diabetes, obesity and a laparotomy for perforated
      sigmoid diverticular disease complicated by a large parastomal hernia. CT
      revealed this subcutaneous abscess to track intra-abdominally through the liver
      and communicate with the gallbladder fossa. The abscess was incised and drained.
      The wound initially drained pus, and then bile. Magnetic resonance
      cholangiopancreatogram (MRCP) demonstrated a remnant gallbladder containing 2
      gallstones, a cholecystocutaneous fistula, portal vein thrombosis and cavernous
      transformation of the bile duct. The patient improved and was discharged. The
      patient's case history and imaging were discussed with the tertiary referral
      centre, in a multidisciplinary team. After an extensive and balanced discussion,
      the patient declined a completion cholecystectomy and continues to have
      occasional discharge from the fistula in her right upper quadrant.

PMID- 27033284
TI  - Spontaneous internal jugular vein thrombosis in rhabdomyosarcoma of the
      nasopharynx.

PMID- 27033285
TI  - Bacillus Calmette-Guerin reactivation as a sign of incomplete Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute, self-limited, systemic vasculitis of unknown
      aetiology, extremely rare in infants younger than 6 months old. Younger infants
      are more likely to present with incomplete KD (IKD) and are at higher risk of
      developing coronary abnormalities. An early and specific clinical sign, not
      included in the classical diagnosis criteria, but that can be very useful in the
      diagnosis of KD, is the reaction at the Bacillus Calmette-Guerin (BCG)
      inoculation site. We describe a case of a 4-month-old boy, fully immunised, whose
      BCG scar reactivation led to the diagnosis of IKD. This case-report emphasises
      the importance of BCG site reactivation in establishing a diagnosis of IKD that
      clinicians should be aware of, especially in countries where BCG vaccination is
      still part of the immunisation schedule.

PMID- 27033286
TI  - Distributive shock, cardiac arrhythmias and multiple organ failure following
      surgery of a fourth ventricular epidermoid.
AB  - A 33-years-old male patient presented with cardiac arrhythmias, acute shock and
      multiple organ dysfunction after the surgical removal of a massive epidermoid
      posterior to the brainstem. The patient initially presented with paraesthesia
      along the right C6 dermatome due to a big tumour at the brain stem. Surgical
      removal was performed without adverse events and he was transferred to our
      intensive care unit (ICU) immediately after the operation. Though initially
      showing a stable postsurgical course he developed cardiac arrhythmias and a state
      of acute distributive shock with consecutive multi organ failure. Extensive
      diagnostic measures could not identify a specific cause for this rapid
      deterioration. However, under carefully monitored symptomatic therapy the patient
      improved quickly, was extubated 72 h after admission and discharged from the ICU
      6 days later. The follow-up did not show any persisting neurological deficits and
      no evidence of a residual tumour in the MRI-study.

PMID- 27033287
TI  - Lower gastrointestinal bleeding in the elderly: a rare aetiology masquerading as
      a diverticular bleed.
AB  - Bleeding per rectum is a relatively common acute surgical presentation. Common
      causes include diverticular disease, colitis, haemorrhoids, polyps, etc. An 83
      year-old man with a history of recurrent rectosigmoid diverticulitis and
      bilateral internal iliac artery aneurysms for 2 years presented with rectal
      bleeding. He was suspected to have a diverticular bleed based on history and
      examination. A CT scan revealed a large haematoma adjacent to the right isolated
      internal iliac artery aneurysm (IIIAA) almost indistinguishable from the adjacent
      rectosigmoid, consistent with a ruptured IIIAA and an ileorectal fistula. The
      fistula was of a primary vascular enteric type and was accentuated by the
      inflammation arising from the diverticulitis. Hence, presence of more common or
      apparently obvious causes should not deter clinicians from thoroughly
      investigating the case. Rare causes should be kept in mind while dealing with
      common acute presentations, especially in elderly patients with multiple
      comorbidities.

PMID- 27033288
TI  - A curious case of stress fracture in a transsexual athlete.
AB  - Femoral neck stress fractures in young healthy individuals are rare and occur in
      those who take part in physical training with repetitive loading and those with
      osteoporosis. Bone density is related to sex hormone status, which is
      artificially manipulated during gender reassignment. Conflicting evidence
      currently exists on the effect of cross sex hormone treatment on bone density,
      with no literature suggesting a link between hormone treatment in gender
      reassignment and stress fractures. Our aim is to highlight the potential risk of
      stress fractures amongst transsexual patients receiving cross sex hormones as
      part of gender reassignment. The patient presented with groin pain after
      competing in a running event. Despite a number of risk factors, there was a delay
      in diagnosis, which could have led to complications compromising outcome. Femoral
      neck stress fractures should be considered in the differential diagnosis of
      transsexual patients receiving hormone treatment with non-specific groin/thigh
      pain following exercise. 

PMID- 27033289
TI  - Neonatal ventricular fibrillation and an elusive ALCAPA: things are not always as
      they seem.
AB  - An anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare
      congenital cardiac condition that typically presents with poor feeding and
      failure to thrive from progressive myocardial ischaemia. Previous reports of
      ALCAPA presenting with ventricular fibrillation (VF) have suggested a causative
      relationship. In this case, we present a neonate with VF without apparent cause
      after an extensive evaluation. Following implantable cardioverter-defibrillator
      placement for presumed idiopathic VF, at which time she also underwent surgical
      ligation of a patent ductus arteriosus (PDA), the neonate developed haemodynamic
      instability that ultimately was found to be due to ALCAPA. Numerous
      echocardiograms had missed the ALCAPA in the setting of mildly elevated pulmonary
      artery pressure. We discuss the limitations of current ultrasound technology in
      diagnosing ALCAPA in the setting of pulmonary hypertension and explain why the
      relationship between this patient's diagnosis of ALCAPA and her episode of VF is
      not clearly causative. 

PMID- 27033290
TI  - T-wave inversions with a difference.

PMID- 27033291
TI  - Hepatosplenic T-cell lymphoma in a young immunocompetent man.
AB  - Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive type of peripheral T
      cell lymphoma that is characterised by extranodal disease, with infiltration and
      proliferation of malignant T-cells within the liver, spleen and bone marrow. The
      authors report the case of a young immunocompetent man, who was admitted to the
      hospital with a history of prolonged, unexplained fever, fatigue and weight loss.
      Initial blood work showed mild pancytopaenia and imaging studies revealed
      hepatosplenomegaly. The diagnosis was challenging, initially mimicking infectious
      disease, and it required an extensive investigation that ultimately revealed the
      characteristic clinical, histopathological and cytogenetic features of HSTCL. The
      clinical course was aggressive, and despite multiagent chemotherapy, the patient
      died 4 months after the diagnosis. This case highlights the difficulty of
      diagnosing HSTCL and the importance of considering it in a differential diagnosis
      of hepatosplenomegaly in young men who present with constitutional symptoms and
      no lymphadenopathy.

PMID- 27033292
TI  - Mimicker of necrotising fasciitis with systemic inflammatory response syndrome:
      recurrent necrotising Sweet's syndrome associated with chronic myelogenous
      leukaemia.
AB  - A 73-year-old man presented with severe right upper quadrant abdominal pain,
      overlying erythema, hypotension and fever. CT scan revealed fasciitis and
      myositis of the right rectus abdominis muscle with subcutaneous inflammation
      involving the fasciae and muscle. Laboratory studies showed extreme leucocytosis.
      The combination of his symptoms, CT findings and laboratory results suggested
      necrotising fasciitis with systemic inflammatory response syndrome. Subsequent
      negative cultures on skin and muscle biopsy led to a diagnosis of necrotising
      neutrophilic panniculitis. Recurrent episodes of fever, and abdominal and
      buttocks pain at various sites, suggested an underlying haematological condition.
      Bone marrow biopsy and genetic analysis revealed chronic myelogenous leukaemia.
      The patient's symptoms of Sweet's syndrome resolved with glucocorticoid treatment
      and did not recur after starting treatment with a tyrosine kinase inhibitor. 

PMID- 27033293
TI  - An anterior jugular vein variant in a patient requiring tracheostomy,
      demonstrating the importance of preoperative/procedural ultrasound.
AB  - A 50-year-old woman was admitted to the intensive care unit (ICU) for a life
      threatening exacerbation of asthma requiring intubation and ventilation for 7
      days. On day 8, she was stepped down from the ventilator via the insertion of a
      tracheostomy to aid weaning. It was initially decided that a percutaneous
      tracheostomy would be attempted on ICU, however, following further consideration,
      it was decided that due to anatomical factors (short neck) a surgical
      tracheostomy would be performed by the ear, nose and throat (ENT) team. A
      periprocedural USS was not performed. At surgery, instead of identifying two
      superficial anterior jugular veins lying on each side of the trachea, one large
      anterior jugular vein (median vein) was found overlying the entire anterior
      surface of the trachea. Had a PCT been attempted without an ultrasound scan being
      performed, this vessel would have been punctured, creating a significant bleed
      that could have placed the patient's airway and/or circulatory system at risk.

PMID- 27033294
TI  - Cerebellar atrophy and muscle weakness: late-onset Tay-Sachs disease outside
      Jewish populations.

PMID- 27033295
TI  - PHACE syndrome with lip haemangioma, microphthalmos and persistent fetal
      vasculature.
AB  - An 11-month-old baby girl presented with white reflex in her left eye. On
      examination, there was a 6.5*5 mm(2)haemangioma present over her face involving
      on her lower lip. Systemic examinations were within normal limits. The left eye
      was small, with an axial length of 16.08 mm and had a cataract. Ultrasonography
      of the left eye was suggestive of the presence of a vascular stalk, persistent
      hyperplasia of a primary vitreous, or persistent fetal vasculature with vitreous
      haemorrhage. On MRI, the left eye was small with vitreous haemorrhage. Left eye
      lens aspiration was performed and the bleeding vascular stalk behind the lens was
      cauterised with diathermy. The right eye was normal. The patient was diagnosed as
      having PHACE syndrome (Posterior fossa malformations, Hemangiomas, Arterial
      anomalies, Coarctation of the aorta and other cardiac defects, and Eye
      abnormalities syndrome). On follow-up, she was able to follow light with her left
      eye.

PMID- 27033296
TI  - Cervical vertebral actinomycosis mimicking malignancy in a paediatric patient.
AB  - Actinomyces spp are found in the flora of the oral cavity and vagina and may
      cause infection with abscess formation and draining sinuses. Cervicofacial
      manifestations of actinomycosis involve head and neck soft tissue, however,
      spread to the cervical spine is rare. We report a case of an 8-year-old boy,
      presenting with neck pain for 1 month and denying a history of trauma or
      procedures. Radiography revealed an ulceration of the posterior oropharyngeal
      mucosa with a defect extending to the C1-C2 vertebra, mimicking a neoplastic
      process. The patient underwent laryngoscopy and multiple biopsies were taken from
      the ulcer and bone, showing severe osteomyelitis and intraosseous filamentous
      organisms, morphologically consistent with Actinomyces spp. The boy received long
      term antibiotics with response to treatment. Actinomycosis has rarely been
      reported in the cervical vertebrae of paediatric patients. This should be
      considered as a differential diagnosis for such a presentation as prompt
      antibiotic treatment may be lifesaving.

PMID- 27033297
TI  - Abdominal wall metastasis following open nephroureterectomy for upper tract
      urothelial carcinoma in a patient with Lynch syndrome.
AB  - A 74-year-old man developed the rare complication of an abdominal wall metastasis
      following open nephroureterectomy for upper tract urothelial carcinoma (UTUC).
      This occurred in the setting of synchronous contralateral ureteric and
      metachronous colorectal carcinomas. Immunohistochemistry demonstrated loss of the
      mutS homolog 6 (MSH6) mismatch repair (MMR) protein in the metastatic abdominal
      wall and colonic lesions, which in conjunction with meeting the Amsterdam II
      criteria, is strongly suggestive of Lynch syndrome (LS). Surgical resection of
      the recurrence was performed with clear margins and neither recurrence nor spread
      during short-term follow-up. 

PMID- 27033298
TI  - Combined particle-image velocimetry and force analysis of the three-dimensional
      fluid-structure interaction of a natural owl wing.
AB  - Low-speed aerodynamics has gained increasing interest due to its relevance for
      the design process of small flying air vehicles. These small aircraft operate at
      similar aerodynamic conditions as, e.g. birds which therefore can serve as role
      models of how to overcome the well-known problems of low Reynolds number flight.
      The flight of the barn owl is characterized by a very low flight velocity in
      conjunction with a low noise emission and a high level of maneuverability at
      stable flight conditions. To investigate the complex three-dimensional flow field
      and the corresponding local structural deformation in combination with their
      influence on the resulting aerodynamic forces, time-resolved stereoscopic
      particle-image velocimetry and force and moment measurements are performed on a
      prepared natural barn owl wing. Several spanwise positions are measured via PIV
      in a range of angles of attack [Formula: see text] 6 degrees  and Reynolds
      numbers 40 000 [Formula: see text] 120 000 based on the chord length.
      Additionally, the resulting forces and moments are recorded for -10 degrees  <=
      alpha <= 15 degrees  at the same Reynolds numbers. Depending on the spanwise
      position, the angle of attack, and the Reynolds number, the flow field on the
      wing's pressure side is characterized by either a region of flow separation,
      causing large-scale vortical structures which lead to a time-dependent deflection
      of the flexible wing structure or wing regions showing no instantaneous
      deflection but a reduction of the time-averaged mean wing curvature. Based on the
      force measurements the three-dimensional fluid-structure interaction is assumed
      to considerably impact the aerodynamic forces acting on the wing leading to a
      strong mechanical loading of the interface between the wing and body. These time
      depending loads which result from the flexibility of the wing should be taken
      into consideration for the design of future small flying air vehicles using
      flexible wing structures. 

PMID- 27033300
TI  - High-throughput screening of antibiotic-resistant bacteria in picodroplets.
AB  - The prevalence of clinically-relevant bacterial strains resistant to current
      antibiotic therapies is increasing and has been recognized as a major health
      threat. For example, multidrug-resistant tuberculosis and methicillin-resistant
      Staphylococcus aureus are of global concern. Novel methodologies are needed to
      identify new targets or novel compounds unaffected by pre-existing resistance
      mechanisms. Recently, water-in-oil picodroplets have been used as an alternative
      to conventional high-throughput methods, especially for phenotypic screening.
      Here we demonstrate a novel microfluidic-based picodroplet platform which enables
      high-throughput assessment and isolation of antibiotic-resistant bacteria in a
      label-free manner. As a proof-of-concept, the system was used to isolate fusidic
      acid-resistant mutants and estimate the frequency of resistance among a
      population of Escherichia coli (strain HS151). This approach can be used for
      rapid screening of rare antibiotic-resistant mutants to help identify novel
      compound/target pairs.

PMID- 27033299
TI  - Modelling intracellular competition for calcium: kinetic and thermodynamic
      control of different molecular modes of signal decoding.
AB  - Frequently, a common chemical entity triggers opposite cellular processes, which
      implies that the components of signalling networks must detect signals not only
      through their chemical natures, but also through their dynamic properties. To
      gain insights on the mechanisms of discrimination of the dynamic properties of
      cellular signals, we developed a computational stochastic model and investigated
      how three calcium ion (Ca(2+))-dependent enzymes (adenylyl cyclase (AC),
      phosphodiesterase 1 (PDE1), and calcineurin (CaN)) differentially detect Ca(2+)
      transients in a hippocampal dendritic spine. The balance among AC, PDE1 and CaN
      might determine the occurrence of opposite Ca(2+)-induced forms of synaptic
      plasticity, long-term potentiation (LTP) and long-term depression (LTD). CaN is
      essential for LTD. AC and PDE1 regulate, indirectly, protein kinase A, which
      counteracts CaN during LTP. Stimulations of AC, PDE1 and CaN with artificial and
      physiological Ca(2+) signals demonstrated that AC and CaN have Ca(2+)
      requirements modulated dynamically by different properties of the signals used to
      stimulate them, because their interactions with Ca(2+) often occur under kinetic
      control. Contrarily, PDE1 responds to the immediate amplitude of different Ca(2+)
      transients and usually with the same Ca(2+) requirements observed under steady
      state. Therefore, AC, PDE1 and CaN decode different dynamic properties of Ca(2+)
      signals.

PMID- 27033301
TI  - Reasons for Removal of Emergency Department-Inserted Peripheral Intravenous
      Cannulae in Admitted Patients: A Retrospective Medical Chart Audit in Australia.

PMID- 27033302
TI  - Multidimensional approach to teaching anatomy-Do gender and learning style
      matter?
AB  - BACKGROUND: The aim of this study was to assess the impact of two teaching
      interventions (ultrasound and arthroscopy) in a peer teaching (PT) environment on
      anatomy examination scores and also to examine the influence of gender and
      learning style on these scores. METHODS: We randomly assigned 484 second year
      medical students to one of three groups: musculoskeletal ultrasound (MSUS),
      arthroscopy (ASC) and control (CON). The MSUS- and the ASC-group attended two
      additional training sessions in ultrasound or arthroscopy; the CON-group received
      no additional lessons. Students were asked to complete Kolb's Learning Style
      Inventory test. We assessed differences in anatomical knowledge (multiple choice
      (MC) exam) and subjective evaluation with respect to gender and learning style.
      RESULTS: There were no relevant differences between the three groups regarding
      the MC exam. Acceptance of the peer teaching concept was good. All students
      preferred ultrasound to arthroscopy and thought that they learned more from
      ultrasound despite the fact that they rated the instructors as less competent and
      needed more time to gain in-depth knowledge. There was no significant effect of
      gender on evaluation results. Arthroscopy was best enjoyed by accommodators
      according to Kolb's Inventory and least by divergers, who found that they had
      learned a lot through ultrasound. The improvement in spatial conceptualization
      was greatest for accommodators and worst for assimilators. CONCLUSION: Gender and
      learning style had no impact on quantitative parameters. Qualitative analysis,
      however, revealed differences for learning style and further evaluation is
      warranted to assess the impact on medical education.

PMID- 27033303
TI  - Coupling between protonation and conformation in cytochrome c oxidase: Insights
      from constant-pH MD simulations.
AB  - Cytochrome c oxidases (CcOs) are the terminal enzymes of the respiratory chain in
      mitochondria and most bacteria. These enzymes reduce dioxygen (O(2)) to water
      and, simultaneously, generate a transmembrane electrochemical proton gradient.
      Despite their importance in the aerobic metabolism and the large amount of
      structural and biochemical data available for the A1-type CcO family, there is
      still no consensually accepted description of the molecular mechanisms operating
      in this protein. A substantial number of questions about the CcO's working
      mechanism remain to be answered, including how the protonation behavior of some
      key residues is modulated during a reduction cycle and how is the conformation of
      the protein affected by protonation. The main objective of this work was to study
      the protonation-conformation coupling in CcOs and identify the molecular factors
      that control the protonation state of some key residues. In order to directly
      capture the interplay between protonation and conformational effects, we have
      performed constant-pH MD simulations of an A1-type CcO inserted into a lipid
      bilayer in two redox states (oxidized and reduced) at physiological pH. From the
      simulations, we were able to identify several groups with unusual titration
      behavior that are highly dependent on the protein redox state, including the A
      propionate from heme a and the D-propionate from heme a3, two key groups possibly
      involved in proton pumping. The protonation state of these two groups is heavily
      influenced by subtle conformational changes in the protein (notably of R481(I)
      and R482(I)) and by small changes in the hydrogen bond network.

PMID- 27033304
TI  - Emerging role of Lon protease as a master regulator of mitochondrial functions.
AB  - Lon protease is a nuclear-encoded, mitochondrial ATP-dependent protease highly
      conserved throughout the evolution, crucial for the maintenance of mitochondrial
      homeostasis. Lon acts as a chaperone of misfolded proteins, and is necessary for
      maintaining mitochondrial DNA. The impairment of these functions has a deep
      impact on mitochondrial functionality and morphology. An altered expression of
      Lon leads to a profound reprogramming of cell metabolism, with a switch from
      respiration to glycolysis, which is often observed in cancer cells. Mutations of
      Lon, which likely impair its chaperone properties, are at the basis of a genetic
      inherited disease named of the cerebral, ocular, dental, auricular, skeletal
      (CODAS) syndrome. This article is part of a Special Issue entitled 'EBEC 2016:
      19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016',
      edited by Prof. Paolo Bernardi. 

PMID- 27033305
TI  - Probing S-state advancements and recombination pathways in photosystem II with a
      global fit program for flash-induced oxygen evolution pattern.
AB  - The oxygen-evolving complex (OEC) in photosystem II catalyzes the oxidation of
      water to molecular oxygen. Four decades ago, measurements of flash-induced oxygen
      evolution have shown that the OEC steps through oxidation states S(0), S(1),
      S(2), S(3) and S(4) before O(2) is released and the S(0) state is reformed. The
      light-induced transitions between these states involve misses and double hits.
      While it is widely accepted that the miss parameter is S state dependent and may
      be further modulated by the oxidation state of the acceptor side, the traditional
      way of analyzing each flash-induced oxygen evolution pattern (FIOP) individually
      did not allow using enough free parameters to thoroughly test this proposal.
      Furthermore, this approach does not allow assessing whether the presently known
      recombination processes in photosystem II fully explain all measured oxygen
      yields during Si state lifetime measurements. Here we present a global fit
      program that simultaneously fits all flash-induced oxygen yields of a standard
      FIOP (2 Hz flash frequency) and of 11-18 FIOPs each obtained while probing the
      S(0), S(2) and S(3) state lifetimes in spinach thylakoids at neutral pH. This
      comprehensive data treatment demonstrates the presence of a very slow phase of
      S(2) decay, in addition to the commonly discussed fast and slow reduction of S(2)
      by YD and QB(-), respectively. Our data support previous suggestions that the
      S(0)->S(1) and S(1)->S(2) transitions involve low or no misses, while high misses
      occur in the S(2)->S(3) or S(3)->S(0) transitions.

PMID- 27033306
TI  - The cyanobacterial cytochrome b6f subunit PetP adopts an SH3 fold in solution.
AB  - PetP is a peripheral subunit of the cytochrome b(6)f complex (b(6)f) present in
      both, cyanobacteria and red algae. It is bound to the cytoplasmic surface of this
      membrane protein complex where it greatly affects the efficiency of the linear
      photosynthetic electron flow although it is not directly involved in the electron
      transfer reactions. Despite the crystal structures of the b(6)f core complex,
      structural information for the transient regulatory b(6)f subunits is still
      missing. Here we present the first structure of PetP at atomic resolution as
      determined by solution NMR. The protein adopts an SH3 fold, which is a common
      protein motif in eukaryotes but comparatively rare in prokaryotes. The structure
      of PetP enabled the identification of the potential interaction site for b(6)f
      binding by conservation mapping. The interaction surface is mainly formed by two
      large loop regions and one short 310 helix which also exhibit an increased
      flexibility as indicated by heteronuclear steady-state {(1)H}-(15)N NOE and
      random coil index parameters. The properties of this potential b(6)f binding site
      greatly differ from the canonical peptide binding site which is highly conserved
      in eukaryotic SH3 domains. Interestingly, three other proteins of the
      photosynthetic electron transport chain share this SH3 fold with PetP: NdhS of
      the photosynthetic NADH dehydrogenase-like complex (NDH-1), PsaE of the
      photosystem 1 and subunit alpha of the ferredoxin-thioredoxin reductase have,
      similar to PetP, a great impact on the photosynthetic electron transport.
      Finally, a model is presented to illustrate how SH3 domains modulate the
      photosynthetic electron transport processes in cyanobacteria.

PMID- 27033307
TI  - Mast cells in lymphomas.
AB  - Tumor microenvironment is involved in the pathogenesis and progression of human
      lymphomas. The lymphoma microenvironment is composed by stromal cells, immune
      cells (macrophages, plasma cells, mast cells, eosinophils, basophils, T- and B
      cells), blood vessels and extracellular matrix proteins. This article is focused
      on the role of mast cells in lymphoma progression and angiogenesis. Mast cells
      might be regarded in a future perspective as a new target for the adjuvant
      treatment of tumors, including lymphomas. 

PMID- 27033310
TI  - Tanycytic ependymoma of cervical cord presenting with spontaneous intratumoral
      hemorrhage.

PMID- 27033308
TI  - miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2.
AB  - Cardiac dysfunction with sepsis is a major cause of death in intensive care
      units. Several lines of evidence have revealed the potential of microRNAs
      (miRNAs, miRs) as biomarkers for detecting sepsis, though direct evidence of
      their functional roles in septic cardiac dysfunction is still lacking. In this
      study, C57BL/6 mice were exposed to lipopolysaccharide (LPS) to induce sepsis
      associated cardiac dysfunction, as evidenced by reduced fractional shortening
      (FS) and ejection fraction (EF) and detrimental changes in cardiac contractility,
      inflammation, and energy metabolism. Microarray analysis and qRT-PCRs revealed
      that miR-21-3p was significantly induced in heart samples challenged with LPS.
      Impressively, pharmacological inhibition of miR-21-3p using antagomiR was able to
      preserve FS and EF and prevent mitochondria ultrastructural damage and autophagy
      in LPS-treated mice, while forced expression of miR-21-3p using agomiR aggravated
      that. Besides that, miR-21-3p antagomiR improved the survival of mice treated
      with LPS. Meanwhile, our data showed that SH3 domain-containing protein 2
      (SORBS2) was inversely correlated with miR-21-3p expression level in mice hearts,
      and was repressed in hearts challenged with LPS, suggesting SORBS2 as a target
      gene of miR-21-3p. Additionally, plasma miR-21-3p was markedly elevated in septic
      patients with cardiac dysfunction as compared to septic patients without cardiac
      dysfunction. The ROC curve showed that plasma miR-21-3p could be a specific
      predictor of septic patients developing cardiac dysfunction with an area under
      the curve of 0.939. Collectively, the present study provides strong evidence that
      miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2.
      Inhibition of miR-21-3p might be a protective strategy to treat sepsis-induced
      cardiac dysfunction.

PMID- 27033311
TI  - Are allogeneic blood transfusions associated with decreased survival after
      surgical treatment for spinal metastases?
AB  - BACKGROUND CONTEXT: Perioperative allogeneic blood transfusions have been
      associated with decreased survival after surgical resection of primary and
      metastatic cancer. Studies investigating this association for patients undergoing
      resection of bone metastases are scarce and controversial. PURPOSE: We assessed
      (1) whether exposure to perioperative allogeneic blood transfusions was
      associated with decreased survival after surgery for spinal metastases and (2) if
      there was a dose-response relationship per unit of blood transfused.
      Additionally, we explored the risk factors associated with survival after surgery
      for spinal metastases. STUDY DESIGN/SETTING: This is a retrospective cohort study
      from two university medical centers. PATIENT SAMPLE: There were 649 patients who
      had operative treatment for metastatic disease of the spine between 2002 and
      2014. Patients with lymphoma or multiple myeloma were also included. We excluded
      patients with a revision procedure, kyphoplasty, vertebroplasty, and radiosurgery
      alone. OUTCOME MEASURES: The outcome measure was survival after surgery. The date
      of death was obtained from the Social Security Death Index and medical charts.
      METHODS: Blood transfusions within 7 days before and 7 days after surgery were
      considered perioperative. A multivariate Cox proportional hazard model was used
      to assess the relationship between allogeneic blood transfusion as exposure
      versus non-exposure, and subsequently as continuous value; we accounted for
      clinical, laboratory, and treatment factors. RESULTS: Four hundred fifty-three
      (70%) patients received perioperative blood transfusions, and the median number
      of units transfused was 3 (interquartile range: 2-6). Exposure to perioperative
      blood transfusion was not associated with decreased survival after accounting for
      all explanatory variables (hazard ratio [HR]: 1.03; 95% confidence interval [CI]:
      0.80-1.31; p=.841). Neither did we find a dose-response relationship (HR: 1.01;
      95% CI: 0.98-1.04; p=.420). Other factors associated with worse survival were
      older age, more severe comorbidity status, lower preoperativehemoglobin level,
      higher white blood cell count, higher calcium level, primary tumor type, previous
      systemic therapy, poor performance status, presence of lung, liver, or brain
      metastasis, and surgical approach. CONCLUSIONS: Perioperative allogeneic blood
      transfusions were not associated with decreased survival after surgery for spinal
      metastases. More liberal transfusion policies might be warranted for patients
      undergoing surgery for spinal metastasis, although careful consideration is
      needed as other complications may occur.

PMID- 27033312
TI  - A new extensile anterolateral retroperitoneal approach for lumbar interbody
      fusion from L1 to S1: a prospective series with clinical outcomes.
AB  - BACKGROUND CONTEXT: A variety of surgical approaches have been used for cage
      insertion in lumbar interbody fusion surgery. The direct anterior approach
      requires mobilization of the great vessels to access the intervertebral disc
      spaces cranial to L5/S1. With the lateral retroperitoneal transpsoas approach, it
      is difficult to access the L4/L5 intervertebral disc space due to the lumbar
      plexus and iliac crest, and L5/S1 is inaccessible. We describe a new
      anterolateral retroperitoneal approach, which is safe and reproducible to access
      the disc spaces from L1 to S1 inclusive, obviating the need for a separate direct
      anterior approach to access L5/S1. PURPOSE: This paper had the following
      objectives: first, to report a reproducible novel single-incision, muscle
      splitting, anterolateral pre-psoas surgical approach to the lumbar spine from L1
      to S1; second, to highlight the technical challenges of this approach and
      highlight approach-related complications; and third, to evaluate clinical
      outcomes using this surgical technique in a prospective series of L1 to S1
      anterior lumbar interbody fusions (ALIFs) performed as part of a 360-degree
      fusion for adult spinal deformity correction. STUDY DESIGN: This report used a
      prospective cohort study. PATIENT SAMPLE: A prospective series of patients (n=64)
      having ALIF using porous tantalum cages as part of a two-stage complex spinal
      reconstruction from L1 to S1 were studied. OUTCOME MEASURES: Data collected
      included blood loss, operative time, incision size, technical challenges,
      perioperative complications, and secondary procedures. Clinical outcome measures
      used included visual analogue scale (VAS) Back Pain, VAS Leg Pain, EuroQoL-5
      Dimensions (EQ-5D), EQ-5D VAS, Oswestry Disability Index (ODI), and Scoliosis
      Research Society-22 (SRS-22). METHODS: Pre- and postoperative radiographic
      parameters and clinical outcome measures were assessed. Mean follow-up time was
      1.8 years. RESULTS: Mean blood loss was 68+/-9.6 mL. The mean VAS Back Pain score
      improved from 7.5+/-1.25 preoperatively to 2.5+/-1.7 at 3 months (p=.02), 1.2+/
      0.5 at 6 months (p=.01), and 1.4+/-0.6 at 1 year (p=.02). The mean ODI improved
      from 64.3+/-31.8 preoperatively to 16.6+/-14.7 at 3 months (p>.05), 10.7+/-6.0 at
      6 months (p=.02), and 6.7+/-6.1 at 1 year (p=.01). There were no permanent
      neurologic, vascular, or visceral injuries. One revision anterior procedure was
      required on a patient with rheumatoid arthritis and advanced systemic disease
      that sustained a sacral fracture and required revision ALIF at L5/S1.
      CONCLUSIONS: The technique described is a safe, new, muscle-splitting, psoas
      preserving, one-incision approach to provide access from L1 to S1 for multilevel
      anterior or oblique lumbar interbody fusion surgery.

PMID- 27033313
TI  - p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but
      does not impact on body weight or glucose homeostasis in diet-induced obesity.
AB  - BCL-2 proteins have been implicated in the control of glucose homeostasis and
      metabolism in different cell types. Thus, the aim of this study was to determine
      the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of
      apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using
      PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either
      continued consuming a low fat chow diet (6% fat), or were fed with a high fat
      diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin
      tolerance, insulin response in peripheral tissues, energy expenditure, oxygen
      consumption, and respiratory exchange ratio in vivo. All these parameters were
      indistinguishable between wild type and knockout mice on chow diet and were
      modified equally by diet-induced obesity. Interestingly, we observed decreased
      food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This
      was associated with increased adipocyte size and fasted leptin concentration in
      the blood. Our findings suggest that although PUMA is dispensable for glucose
      homeostasis in lean and obese mice, it can affect leptin levels and food intake
      during obesity. 

PMID- 27033314
TI  - Metal-Insulator Transition Driven by Vacancy Ordering in GeSbTe Phase Change
      Materials.
AB  - Phase Change Materials (PCMs) are unique compounds employed in non-volatile
      random access memory thanks to the rapid and reversible transformation between
      the amorphous and crystalline state that display large differences in electrical
      and optical properties. In addition to the amorphous-to-crystalline transition,
      experimental results on polycrystalline GeSbTe alloys (GST) films evidenced a
      Metal-Insulator Transition (MIT) attributed to disorder in the crystalline phase.
      Here we report on a fundamental advance in the fabrication of GST with out-of
      plane stacking of ordered vacancy layers by means of three distinct methods:
      Molecular Beam Epitaxy, thermal annealing and application of femtosecond laser
      pulses. We assess the degree of vacancy ordering and explicitly correlate it with
      the MIT. We further tune the ordering in a controlled fashion attaining a large
      range of resistivity. Employing ordered GST might allow the realization of cells
      with larger programming windows. 

PMID- 27033315
TI  - MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity.
AB  - Anthracyclines, such as doxorubicin, are well-established, highly efficient anti
      neoplastic drugs used for treatment of a variety of cancers, including solid
      tumors, leukemia, lymphomas, and breast cancer. The successful use of doxorubicin
      has, however, been hampered by severe cardiotoxic side-effects. In order to
      prevent or reverse negative side-effects of doxorubicin, it is important to find
      early biomarkers of heart injury and drug-induced cardiotoxicity. The high
      stability under extreme conditions, presence in various body fluids, and tissue
      specificity, makes microRNAs very suitable as clinical biomarkers. The present
      study aimed towards evaluating the early and late effects of doxorubicin on the
      microRNA expression in cardiomyocytes derived from human pluripotent stem cells.
      We report on several microRNAs, including miR-34a, miR-34b, miR-187, miR-199a,
      miR-199b, miR-146a, miR-15b, miR-130a, miR-214, and miR-424, that are
      differentially expressed upon, and after, treatment with doxorubicin.
      Investigation of the biological relevance of the identified microRNAs revealed
      connections to cardiomyocyte function and cardiotoxicity, thus supporting the
      findings of these microRNAs as potential biomarkers for drug-induced
      cardiotoxicity. 

PMID- 27033316
TI  - Unraveling the biogeographic origins of the Eurasian watermilfoil (Myriophyllum
      spicatum) invasion in North America.
AB  - PREMISE OF THE STUDY: Using phylogeographic analyses to determine the geographic
      origins of biological invaders is important for identifying environmental
      adaptations and genetic composition in their native range as well as biocontrol
      agents among indigenous herbivores. Eurasian watermilfoil (Myriophyllum spicatum)
      and its hybrid with northern watermilfoil (M. sibiricum) are found throughout the
      contiguous United States and southern Canada, forming one of the most
      economically costly aquatic plant invasions in North America, yet the geographic
      origin of the invasion remains unknown. The objectives of our study included
      determining the geographic origin of Eurasian watermilfoil in North America as
      well as the maternal lineage of the hybrids. METHODS: DNA sequence data from a
      cpDNA intron and the nrDNA ITS region were compiled for accessions from 110
      populations of Eurasian watermilfoil and hybrids from North America and the
      native range (including Europe, Asia, and Africa). Datasets were analyzed using
      statistical parsimony and Bayesian phylogenetics to assess the geographic origin
      of the invasion. KEY RESULTS: The two Eurasian watermilfoil cpDNA haplotypes in
      North America are also found from China and Korea, but not elsewhere in the
      native range. These haplotypes did not overlap and were limited in native
      geographic range. The ovule parent for hybrids can come from either parental
      lineage, and multiple haplotypes from both parental species were found.
      CONCLUSIONS: The geographic origin of this prolific aquatic plant invasion of
      North America is in Asia. This provides critical information to better understand
      the invasion pathway and inform management into the future.

PMID- 27033317
TI  - Unraveling the origin of the Appalachian gametophyte, Vittaria appalachiana.
AB  - PREMISE OF STUDY: Ferns and lycophytes are distinct among plants in producing two
      free-living life stages: a long-lived sporophyte phase and a (usually) short
      lived gametophyte phase. Notably, however, some species have perennial,
      vegetatively reproducing gametophytes. Vittaria appalachiana is one of just three
      species in which mature sporophytes are unknown. It has a wide range throughout
      the Appalachian Mountains and Plateau, where it reproduces asexually via gemmae.
      The origin of V. appalachiana, however, has long been a mystery, with most
      previous studies suggesting it may have resulted from hybridization of two
      closely related Vittaria species (V. graminifolia and V. lineata). METHODS: A
      four-gene plastid data set including 32 samples of six Vittaria species, plus
      samples of five outgroup species, was analyzed to uncover phylogenetic
      relationships. Additional analyses of nuclear DET1 gene sequences allowed for the
      examination of hypotheses involving a hybrid origin for V. appalachiana. KEY
      RESULTS: In the plastid phylogeny, V. appalachiana is well supported as
      monophyletic, but is embedded within V. graminifolia. With the exception of a
      single aberrant allele, this result is mirrored in the nuclear tree. CONCLUSIONS:
      Through analyses of plastid and nuclear data sets, this study demonstrates that a
      hybrid origin for V. appalachiana is unlikely. Instead, it appears that this
      species emerged from within the V. graminifolia lineage. Further work is needed
      to fully elucidate the genetic structure within this group.

PMID- 27033318
TI  - The cobra's tongue: Rethinking the function of the "fishtail appendage" on the
      pitcher plant Darlingtonia californica.
AB  - PREMISE OF STUDY: Carnivorous pitcher plants employ a variety of putative
      adaptations for prey attraction and capture. One example is the peculiar forked
      "fishtail appendage", a foliar structure widely presumed to function as a prey
      attractant on adult leaves of Darlingtonia californica (Sarraceniaceae). This
      study tests the prediction that the presence of the appendage facilitates prey
      capture and can be considered an example of an adaptation to the carnivorous
      syndrome. METHODS: In a field experiment following a cohort of Darlingtonia
      leaves over their growing season, before the pitcher traps opened, the fishtail
      appendages from half of the leaves were removed. Additionally, all appendages
      were removed from every plant at two small, isolated populations. After 54 and
      104 d, prey items were collected to determine whether differences in prey
      composition and biomass existed between experimental and unmanipulated control
      leaves. KEY RESULTS: Removal of the fishtail appendage did not reduce pitcher
      leaves' prey biomass nor alter their prey composition at either the level of
      individual leaves or entire populations. Fishtail appendages on plants growing in
      shaded habitats contained significantly greater chlorophyll concentrations than
      those on plants growing in full sun. CONCLUSIONS: These results call into
      question the longstanding assumption that the fishtail appendage on Darlingtonia
      is an adaptation critical for the attraction and capture of prey. I suggest
      alternative evolutionary explanations for the role of the fishtail structure and
      repropose a hypothesis on the mutualistic nature of pitcher plant-arthropod
      trophic interactions.

PMID- 27033319
TI  - [In Process Citation].

PMID- 27033320
TI  - Massage for Low-back Pain.
AB  - FURLAN AD, GIRALDOM, BASKWILL A, IRVIN E, IMAMURA M. MASSAGE FOR LOW-BACK PAIN.
      COCHRANE DATABASE SYST REV 2015, ISSUE 9. ART. NO.: CD001929. DOI:
      10.1002/14651858.CD001929.PUB3. BACKGROUND: Low back pain (LPB) is one of the
      most common and costly musculoskeletal problems in modern society. It is
      experienced by 70-80% of adults at some time in their lives. Massage therapy has
      the potential to minimize pain and speed return to normal function. OBJECTIVES:
      To assess the effects of massage therapy for people with non-specific LBP. SEARCH
      METHODS: We searched PubMed to August 2014, and the following databases to July
      2014: MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Index to Chiropractic Literature,
      and Proquest Dissertation Abstracts.We also checked reference lists. There were
      no language restrictions used. SELECTION CRITERIA: We included only randomized
      controlled trials of adults with non-specific LBP classified as acute, sub-acute,
      or chronic. Massage was defined as soft-tissue manipulation using the hands or
      amechanical device.We grouped the comparison groups into two types: inactive
      controls (sham therapy, waiting list, or no treatment), and active controls
      (manipulation, mobilization, TENS, acupuncture, traction, relaxation, physical
      therapy, and exercises or self-care education). DATA COLLECTION AND ANALYSIS: We
      used standard Cochrane methodological procedures and followed CBN guidelines. Two
      independent authors performed article selection, data extraction, and critical
      appraisal. MAIN RESULTS: In total we included 25 trials (3096 participants) in
      this review update. The majority was funded by not-for-profit organizations. One
      trial included participants with acute LBP, and the remaining trials included
      people with sub-acute or chronic LBP (CLBP). In three trials massage was done
      with a mechanical device, and the remaining trials used only the hands. The most
      common type of bias in these studies was performance and measurement bias because
      it is difficult to blind participants, massage therapists and the measuring
      outcomes. We judged the quality of the evidence to be "low" to "very low," and
      the main reasons for downgrading the evidence were risk of bias and imprecision.
      There was no suggestion of publication bias. For acute LBP, massage was found to
      be better than inactive controls for pain (SMD = -1.24, 95% CI: -1.85 to -.64;
      participants = 51; studies = 1) in the short-term, but not for function (SMD = 
      .50, 95% CI: -1.06 to .06; participants = 51; studies = 1). For sub-acute and
      chronic LBP, massage was better than inactive controls for pain (SMD = -.75, 95%
      CI: -.90 to -.60; participants = 761; studies = 7) and function (SMD = -.72, 95%
      CI: -1.05 to -.39; 725 participants; 6 studies) in the short-term, but not in the
      long-term; however, when compared to active controls, massage was better for
      pain, both in the short (SMD = -.37, 95% CI: -.62 to -.13; participants = 964;
      studies = 12) and long-term follow-up (SMD = -.40, 95% CI: -.80 to -.01;
      participants = 757; studies = 5), but no differences were found for function
      (both in the short and longterm). There were no reports of serious adverse events
      in any of these trials. Increased pain intensity was the most common adverse
      event reported in 1.5-25% of the participants. AUTHORS' CONCLUSIONS: We have very
      little confidence that massage is an effective treatment for LBP. Acute, sub
      acute, and chronic LBP had improvements in pain outcomes with massage only in the
      short-term follow-up. Functional improvement was observed in participants with
      sub-acute and chronic LBP when compared with inactive controls, but only for the
      short-term follow-up. There were only minor adverse effects with massage.

PMID- 27033321
TI  - Relationships, Priorities, and a Life Worth Living.

PMID- 27033324
TI  - Identification of novel inhibitors of the steroid sulfate carrier 'sodium
      dependent organic anion transporter' SOAT (SLC10A6) by pharmacophore modelling.
AB  - The sodium-dependent organic anion transporter SOAT specifically transports
      sulfated steroid hormones and is supposed to play a role in testicular steroid
      regulation and male fertility. The present study aimed to identify novel specific
      SOAT inhibitors for further in vitro and in vivo studies on SOAT function. More
      than 100 compounds of different molecular structures were screened for inhibition
      of the SOAT-mediated transport of dehydroepiandrosterone sulfate in stably
      transfected SOAT-HEK293 cells. Twenty-five of these with IC50 values covering
      four orders of magnitude were selected as training set for 3D pharmacophore
      modelling. The SOAT pharmacophore features were calculated by CATALYST and
      consist of three hydrophobic sites and two hydrogen bond acceptors. By substrate
      database screening, compound T 0511-1698 was predicted as a novel SOAT inhibitor
      with an IC50 of 15 MUM. This value was confirmed by cell-based transport assays.
      Therefore, the developed SOAT pharmacophore model demonstrated its suitability in
      predicting novel SOAT inhibitors.

PMID- 27033323
TI  - Laughter Yoga, Adults Living With Parkinson's Disease, and Caregivers: A Pilot
      Study.
AB  - OBJECTIVE: This study explored outcomes of Laughter Yoga in adults with
      Parkinson's disease (PD) and their caregivers. Laughter has been shown to
      generally improve mood in physically healthy adults, and specifically in adults
      with heart disease or cancer, but little research exists regarding the impact of
      laughter in adults with Parkinson's disease. Low mood is frequently a co-morbid
      condition for adults with Parkinson's disease, and can negatively affect their
      caregivers. DESIGN: Pre-experimental (O1 * O2) pretest-posttest design.
      SETTINGS/LOCATION: Data collection occurred at six unique PD support groups in
      Southern California. SUBJECTS: Participants (N = 85) comprised a convenience
      sample of adults diagnosed with Parkinson's disease (n = 47) and accompanying
      caregivers (n = 38). INTERVENTION: Subjects participated in a 45-min Laughter
      Yoga (LY) session conducted by a Certified Laughter Yoga Teacher. OUTCOME
      MEASURES: This study utilized the Laughter Yoga "How Do You Feel?" (HDYF) form.
      The form consists of a series of 10 scales labeled "well-being" measures
      including enthusiasm, energy level, mood, optimism, stress level, level of
      friendship with group members, level of awareness about breathing, level of
      muscle relaxation, level of mental relaxation, and ability to laugh without a
      reason. RESULTS AND CONCLUSION: Paired sample t-tests reveal statistically
      significant improvements in well-being for adults with PD and their caregivers
      after attending an LY session. Therapists and other clinicians should consider
      utilizing this unique technique with adults with PD to address co-morbid low-mood
      conditions and include caregivers in the LY sessions for support and their own
      benefit.

PMID- 27033325
TI  - Clomiphene citrate down-regulates estrogen receptor-alpha through the ubiquitin
      proteasome pathway in a human endometrial cancer cell line.
AB  - We examined how clomiphene citrate (CC) reduces estrogen receptor-alpha (ERalpha)
      in a human endometrial cancer cell line. Ishikawa human endometrial cancer cells
      were treated with ERalpha ligands such as 17beta-estradiol (E2), CC, and the pure
      antiestrogen, ICI 182,780 (ICI). Thereafter, the expression levels of ERalpha
      protein and mRNA were analyzed by western blot and real-time quantitative PCR,
      respectively, and those of ubiquitinated ERalpha were analyzed by
      immunoprecipitation of ERalpha followed by immunoblotting with an anti-ubiquitin
      antibody. The expression levels of ERalpha protein after treatment with E2, CC,
      and ICI were significantly decreased compared to pre-treatment levels without a
      corresponding decrease in ERalpha mRNA. These ligands significantly increased the
      levels of ubiquitinated ERalpha compared to vehicle treatment. Co-treatment with
      the proteasome inhibitor, MG132, abrogated the decrease in ERalpha levels caused
      by treatment with the ligands only. We demonstrated, for the first time, a CC
      induced decrease in ERalpha mediated by the ubiquitin-proteasome pathway in human
      endometrial cancer cells.

PMID- 27033326
TI  - Angiopoietin-1 attenuates angiotensin II-induced ER stress in glomerular
      endothelial cells via a Tie2 receptor/ERK1/2-p38 MAPK-dependent mechanism.
AB  - Research has indicated that endoplasmic reticulum (ER) stress in endothelial
      cells affects vascular pathologies and induces cellular dysfunction and
      apoptosis. Angiopoietin1 (Angpt1) has been shown to have therapeutic potential in
      some vascular diseases, including chronic kidney disease. This study showed that
      Angpt1 is a powerful factor that attenuated ER stress-induced cellular
      dysfunction and apoptosis in glomerular endothelial cells (GEnCs). Furthermore,
      Angpt1 significantly decreased the angiotensin II (Ang II)-induced expression of
      the ER stress response proteins GRP78, GRP94, p-PERK and CHOP. These results
      suggest that the Angpt1-mediated cellular protection may occur downstream of the
      ER stress response. In addition, both specific inhibitors and siRNAs for Tie2
      reversed these changes, implying the importance of Tie2 receptor activation in
      the signalling pathways that prevent ER stress. The protective effects of Angpt1
      are related to the activation of two downstream signalling pathways, ERK1/2 and
      p38 MAPK. The inhibition of these pathways with specific inhibitors, PD98059 and
      SB203580, respectively, partially increased the expression of chaperones that
      assist in folding proteins in the ER and reduce the protective effects of Angpt1.
      In conclusion, Angpt1 attenuated ER stress-induced cellular dysfunction and
      apoptosis via the Tie2 receptor/ERK1/2-p38 MAPK pathways in GEnCs. This study may
      provide insights into a novel underlying mechanism and a strategy for alleviating
      ER stress-induced injury.

PMID- 27033327
TI  - Comprehensive Profiling of Glycosphingolipid Glycans Using a Novel Broad
      Specificity Endoglycoceramidase in a High-Throughput Workflow.
AB  - The biological function of glycosphingolipids (GSLs) is largely determined by
      their glycan headgroup moiety. This has placed a renewed emphasis on detailed GSL
      headgroup structural analysis. Comprehensive profiling of GSL headgroups in
      biological samples requires the use of endoglycoceramidases with broad substrate
      specificity and a robust workflow that enables their high-throughput analysis. We
      present here the first high-throughput glyco-analytical platform for GSL
      headgroup profiling. The workflow features enzymatic release of GSL glycans with
      a novel broad-specificity endoglycoceramidase I (EGCase I) from Rhodococcus
      triatomea, selective glycan capture on hydrazide beads on a robotics platform,
      2AB-fluorescent glycan labeling, and analysis by UPLC-HILIC-FLD. R. triatomea
      EGCase I displayed a wider specificity than known EGCases and was able to
      efficiently hydrolyze gangliosides, globosides, (n)Lc-type GSLs, and
      cerebrosides. Our workflow was validated on purified GSL standard lipids and was
      applied to the characterization of GSLs extracted from several mammalian cell
      lines and human serum. This study should facilitate the analytical workflow in
      functional glycomics studies and biomarker discovery.

PMID- 27033328
TI  - Somatic Comorbidity in Schizophrenia: Some Possible Biological Mechanisms Across
      the Life Span.
AB  - Schizophrenia is associated with decreased life expectancy (15-25 y) compared to
      the general population, with comorbid somatic diseases and in particular
      cardiovascular diseases being a major cause. Life style and medication probably
      account for much of the increased mortality risk due to somatic diseases in
      schizophrenia, but the evidence implicating biological pathways potentially
      affecting both body and brain is increasing. This includes overlapping genes
      between schizophrenia and somatic diseases, prenatal risk factors such as hypoxia
      and infections, and increased cardiovascular disease risk in drug-naive patients
      at illness onset. Although environmental bias increases throughout the disease
      course, there are also some studies on chronic schizophrenia and postmortem brain
      samples that warrant further attention. In the following, we will attempt to move
      beyond environmental impact and explore some of the shared pathophysiological
      mechanisms potentially underlying both schizophrenia and somatic diseases.

PMID- 27033329
TI  - Cognitive Function in Individuals With Psychosis: Moderation by Adolescent
      Cannabis Use.
AB  - Prior cannabis use, compared to nonuse, is reported to be associated with less
      cognitive impairment in schizophrenia. The age of cannabis use and the persistent
      influence of cannabis use on cognitive function has not been examined across the
      psychosis dimension. Ninety-seven volunteers with psychosis (schizophrenia,
      schizoaffective, or bipolar psychosis) and 64 controls were recruited at the
      Dallas site of the Bipolar-Schizophrenia Network on Intermediate Phenotypes
      consortium. Cannabis use history obtained in a semi-structured manner was used to
      categorize subjects into nonusers, adolescent-onset users, and late-onset users.
      The a priori hypothesis tested was that individuals with psychosis and a history
      of adolescent cannabis use (ACU) would have better global neuropsychological
      performance, as measured by the Brief Assessment of Cognition in Schizophrenia
      (BACS) battery, compared to those with psychosis and no cannabis use history.
      BACS Composite scores were significantly higher in individuals with psychosis
      with ACU compared to individuals with psychosis and no prior cannabis use. In
      subgroup analyses, ACU influenced global cognition in the
      schizophrenia/schizoaffective (SCZ) subgroup but not the bipolar psychosis
      subgroup. Exploratory analyses within the SCZ group, suggest that ACU was
      associated with better performance in specific domains compared to non-ACU
      groups. There are distinct associations between age of cannabis use and
      neuropsychological function across psychotic illnesses. Specifically, ACU is
      associated with better cognitive function in SCZ but not bipolar psychosis. This
      age-dependent and diagnosis-specific influence of cannabis may need to be
      factored into the design of future cognitive studies in SCZ.

PMID- 27033331
TI  - An Advanced Quantitative Echosound Methodology for Femoral Neck Densitometry.
AB  - The aim of this paper was to investigate the clinical feasibility and the
      accuracy in femoral neck densitometry of the Osteoporosis Score (O.S.), an
      ultrasound (US) parameter for osteoporosis diagnosis that has been recently
      introduced for lumbar spine applications. A total of 377 female patients (aged 61
      70 y) underwent both a femoral dual X-ray absorptiometry (DXA) and an echographic
      scan of the proximal femur. Recruited patients were sub-divided into a reference
      database used for ultrasound spectral model construction and a study population
      for repeatability assessments and accuracy evaluations. Echographic images and
      radiofrequency signals were analyzed through a fully automatic algorithm that
      performed a series of combined spectral and statistical analyses, providing as a
      final output the O.S. value of the femoral neck. Assuming DXA as a gold standard
      reference, the accuracy of O.S.-based diagnoses resulted 94.7%, with k = 0.898 (p
      < 0.0001). Significant correlations were also found between O.S.-estimated bone
      mineral density and corresponding DXA values, with r(2) up to 0.79 and root mean
      square error = 5.9-7.4%. The reported accuracy levels, combined with the proven
      ease of use and very good measurement repeatability, provide the adopted method
      with a potential for clinical routine application in osteoporosis diagnosis.

PMID- 27033330
TI  - A Two-Criterion Model for Microvascular Bio-Effects Induced In Vivo by Contrast
      Microbubbles Exposed to Medical Ultrasound.
AB  - The mechanical index (MI) is a theoretical exposure parameter for cavitational
      bio-effects of diagnostic ultrasound. The theory for the MI assumed that bubbles
      of all relevant sizes exist in tissue, a condition that is approximated for
      tissues that include a microbubble contrast agent. Therefore, the MI should allow
      science-based safety guidance for contrast-enhanced diagnostic ultrasound.
      However, theoretical predictions of bio-effects thresholds based on the MI
      typically do not concur with the frequency dependence of experimentally measured
      thresholds for bio-effects. For example, experimental thresholds for glomerular
      capillary hemorrhage in rats infused with contrast microbubbles increased
      approximately linearly with frequency, whereas the MI predicted a square root
      dependence. Here, cavitation thresholds were computed for linear versions of the
      acoustic pulses used in that study assuming bubbles containing either air, C3F8,
      or a 1:1 mixture of the two and surrounded by either blood or kidney tissue.
      Although no single threshold criterion was successful, combining results for one
      criterion that maximized circumferential stress in the capillary wall with
      another that ensured an inertial collapse produced thresholds that were
      consistent with experimental data. This suggests that a contrast-specific safety
      metric may be achieved following validation of this two-criterion model.

PMID- 27033332
TI  - Detection of Early Tumor Response to Axitinib in Advanced Hepatocellular
      Carcinoma by Dynamic Contrast Enhanced Ultrasound.
AB  - This study aimed to evaluate the utility of dynamic contrast-enhanced ultrasound
      (DCE-US) in measuring early tumor response of advanced hepatocellular carcinoma
      to axitinib. Twenty patients were enrolled (aged 18-78 y; median 65). DCE-US was
      performed with bolus injection and infusion/disruption replenishment. Median
      overall survival was 7.1 mo (1.8-27.3) and progression free survival was 3.6 mo
      (1.8-17.4). Fifteen patients completed infusion scans and 12 completed bolus
      scans at 2 wk. Among the perfusion parameters, fractional blood volume at
      infusion (INFBV) decreased at 2 wk in 10/15 (16%-81% of baseline, mean 47%) and
      increased in 5/15 (116%-535%, mean 220%). This was not significantly associated
      with progression free survival (p = 0.310) or progression at 16 wk (p = 0.849),
      but was borderline statistically significant (p = 0.050) with overall survival,
      limited by a small sample size. DCE-US is potentially useful in measuring early
      tumor response of advanced hepatocellular carcinoma to axitinib, but a larger
      trial is needed.

PMID- 27033333
TI  - Interventions for treating ankle fractures in children.
AB  - BACKGROUND: Ankle fractures, which usually occur after a twisting incident, are a
      diverse collection of injuries with different levels of complexity and severity.
      They have an incidence of 1 in 1000 a year in children. Treatment generally
      involves splints and casts for minor fractures and surgical fixation with screws,
      plates and pins followed by immobilisation for more serious fractures.
      OBJECTIVES: To assess the effects (benefits and harms) of different interventions
      for treating ankle fractures in children. SEARCH METHODS: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (22 September
      2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue
      8), MEDLINE (1946 to September Week 2 2015), MEDLINE In-Process & Other Non
      Indexed Citations (21 September 2015), EMBASE (1980 to 2015 Week 38), CINAHL
      (1937 to 22 September 2015), trial registers (17 February 2015), conference
      proceedings and reference lists of articles. SELECTION CRITERIA: We included
      randomised and quasi-randomised controlled trials evaluating interventions for
      treating ankle fractures in children. DATA COLLECTION AND ANALYSIS: Two review
      authors independently screened titles, abstracts and full articles for inclusion,
      assessed risk of bias and collected data. We undertook no meta-analysis. MAIN
      RESULTS: We included three randomised controlled trials reporting results for 189
      children, all of whom had a clinical diagnosis of a "low risk" ankle fracture.
      These were predominantly classified as undisplaced Salter-Harris type I fractures
      of the distal fibula. All three trials compared non-surgical management options.
      The three trials were at high risk of bias, primarily relating to the
      impracticality of blinding participants and treating clinicians to the allocated
      interventions.Two trials compared the Aircast Air-Stirrup ankle brace versus a
      rigid cast, which was a removable fibreglass posterior splint in one trial (trial
      A) and a below-knee fibreglass walking cast in the other trial (trial B). In
      trial A, both devices were removed at around two weeks. In trial B, removal of
      the brace was optional after five days, while the walking cast was removed after
      three weeks. There was low-quality evidence of clinically important differences
      in function scores at four weeks in favour of the brace groups of both trials.
      Function was measured using the Activities Scale for Kids-performance (ASKp;
      score range 0 to 100, higher scores mean better function) in trial A and using a
      modified version of the ASKp score (range 0 to 100%, higher percentages mean
      better function) in trial B. The results for trial A (40 participants) were
      median 91.9 in the brace group versus 84.2 in the splint group. The results for
      trial B (104 participants) were 91.3% versus 85.3%; mean difference (MD) 6.00%
      favouring brace (95% confidence interval (CI) 1.38% to 10.62%). Trial B indicated
      that 5% amounted to a clinically relevant difference in the modified ASKp score.
      Neither trial reported on unacceptable anatomy or related outcomes or long-term
      follow-up. There was very low-quality evidence relating to adverse events, none
      of which were serious. Trial A found twice as many children with pressure-related
      complications in the brace group (10 of 20 versus 5 of 20). In contrast, trial B
      found four times as many children in the cast group had adverse outcomes assessed
      in terms of an unscheduled visit to a healthcare provider (4 of 54 versus 16 of
      50). Both trials linked some of the adverse events in the brace group with the
      failure to wear a protective sock. There was very low-quality evidence indicating
      an earlier return to pre-injury activity in the brace groups in both trials.
      Trial B provided low-quality evidence that children much prefer five days or more
      wearing an ankle brace than three weeks immobilised in a walking ankle cast.
      There was moderate-quality evidence of a lack of difference between the two
      groups in pain at four weeks.The third trial compared the Tubigrip bandage plus
      crutches and advice versus a plaster of Paris walking cast for two weeks and
      reported results at four weeks' follow-up for 45 children with an inversion
      injury of the ankle. The trial found very low-quality evidence of little
      difference in pain and function between the two groups, measured using a non
      validated pain and function score at four weeks. The trial did not report on
      adverse effects. There was very low-quality evidence of an earlier return to
      normal activities, averaging six days, in children treated with Tubigrip (mean
      14.17 days for Tubigrip versus 20.19 days for cast; MD -6.02 days, 95% CI -8.92
      to -3.12 days).Recent evidence from magnetic resonance imaging studies of the
      main category of injury evaluated in these three trials suggests that most of the
      injuries in these trials were sprains or bone bruises rather than fractures of
      the distal fibular growth plate. AUTHORS' CONCLUSIONS: There is low-quality
      evidence of a quicker recovery of self reported function at four weeks in
      children with clinically diagnosed low-risk ankle fractures who are treated with
      an ankle brace compared with those treated with a rigid cast, especially a non
      removable walking cast. There is otherwise a lack of evidence from randomised
      controlled trials to inform clinical practice for children with ankle fractures.
      Research to identify and address priority questions on the treatment of these
      common fractures is needed.

PMID- 27033336
TI  - Improving Sepsis Recognition and Utilization of Early Goal-Directed Therapy in
      the Prehospital Environment: A Review of the Literature.

PMID- 27033335
TI  - A Quality Improvement Initiative for Designing and Implementing a Military
      Service Screening Tool for a Community Emergency Department.
AB  - PROBLEM: Veterans eligible for health care in the Veterans Administration (VA)
      health system often receive care in community emergency Departments. In line with
      initiatives from Joining Forces and the American Academy of Nursing, emergency
      departments have an opportunity to screen for veterans during routine ED visits
      and provide resource information regarding various VA services. METHODS: Our aims
      were to design and implement a screening process to identify veterans during an
      ED visit, notify ED providers of veteran status, and develop a Veteran Resource
      Guide to be distributed at the time of discharge. We embedded the mandatory
      question, "Have you ever served in the military?" in the electronic medical
      record (EMR). This question was asked of all patients 18 years and older.
      RESULTS: During an 80-day period, we screened 9364 patients and identified 415
      veterans who would not be known to the providers using standard methods. We were
      able to deliver the Veteran Resource Guide to 77 of the 277 veterans discharged
      home. IMPLICATIONS FOR PRACTICE: The addition of the mandatory question about
      military service to the EMR during the primary care assessment successfully
      identified veterans who presented for care in a community emergency department.
      Future initiatives should include automated processes to ensure that the Veteran
      Resource Guide is provided and to foster collaboration between community
      emergency departments and the VA.

PMID- 27033334
TI  - Preclinical evaluation of RNAi as a treatment for transthyretin-mediated
      amyloidosis.
AB  - ATTR amyloidosis is a systemic, debilitating and fatal disease caused by
      transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically
      validated technology that may be a promising approach to the treatment of ATTR
      amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is
      expressed and synthesized in the liver. RNAi technology enables robust hepatic
      gene silencing, the goal of which would be to reduce systemic levels of TTR and
      mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR
      expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a
      murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic
      TTR expression inhibited TTR deposition and facilitated regression of existing
      TTR deposits in pathologically relevant tissues. Further, the extent of deposit
      regression correlated with the level of RNAi-mediated knockdown. In comparison to
      the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater
      regression of TTR deposits across a broader range of affected tissues. Together,
      the data presented herein support the therapeutic hypothesis behind TTR lowering
      and highlight the potential of RNAi in the treatment of patients afflicted with
      ATTR amyloidosis. 

PMID- 27033337
TI  - Against Medical Advice: A Survey of ED Clinicians' Rationale for Use.

PMID- 27033338
TI  - Emergency Nurses' Perceptions of Providing End-of-Life Care in a Hong Kong
      Emergency Department: A Qualitative Study.
AB  - INTRODUCTION: Provision of end-of-life (EOL) care in the emergency department has
      improved globally in recent years and has a different scope of interventions than
      traditional emergency medicine. In 2010, a regional hospital established the
      first ED EOL service in Hong Kong. METHODS: The aim of this study was to
      understand emergency nurses' perceptions regarding the provision of EOL care in
      the emergency department. A qualitative approach was used with purposive sampling
      of 16 nurses who had experience in providing EOL care. Semi-structured, face-to
      face interviews were conducted from May to October, 2014. All the interviews were
      transcribed verbatim for content analysis. RESULTS: Four themes were identified:
      (1) doing good for the dying patients, (2) facilitating family engagement and
      involvement, (3) enhancing personal growth and professionalism, and (4)
      expressing ambiguity toward resource deployment. DISCUSSION: Provision of EOL
      care in the emergency department can enhance patients' last moment of life,
      facilitate the grief and bereavement process of families, and enhance the
      professional development of staff in emergency department. It is substantiated
      that EOL service in the emergency department enriches EOL care in the health care
      system. Findings from this study integrated the perspectives on ED EOL services
      from emergency nurses. The integration of EOL service in other emergency
      departments locally and worldwide is encouraged.

PMID- 27033339
TI  - Acupuncture in Premenopausal Women With Hypoactive Sexual Desire Disorder: A
      Prospective Cohort Pilot Study.
AB  - INTRODUCTION: Female sexual dysfunction affects up to 43% of women in the United
      States and hypoactive sexual desire disorder (HSDD) is the most common type;
      however, we lack treatment options showing improvement for this condition. AIMS:
      To investigate whether acupuncture therapy could improve HSDD. METHODS:
      Premenopausal women with a primary diagnosis of HSDD were included in a single
      arm prospective pilot study that was approved by the institutional review board.
      After providing informed consent, subjects completed validated questionnaires.
      Participants underwent 25-minute twice-weekly acupuncture sessions for 5 weeks
      with one certified acupuncturist. Questionnaires were completed again 6 weeks
      after onset of treatment. MAIN OUTCOME MEASURES: Based on a statistically
      significant change in the desire domain of the Female Sexual Function Index from
      2.0 (at baseline) to 2.4 (after intervention with a specialist) in our population
      of patients diagnosed with HSDD, a sample of 13 was determined, with 90% power
      and alpha 0.05. RESULTS: Fifteen women were enrolled and 13 completed the study.
      Mean age was 36.9 +/- 11.4 years. Most were white (n = 9, 60%), heterosexual (n =
      15, 100%), and non-smokers (n = 14, 93%). Most were sexually active more than
      four times per month (n = 8, 53%) and none had a history of sexual abuse (n = 15,
      100%). Participants received a mean acupuncture needle application of 17 +/- 2 at
      each session. Sexual function improved after intervention, particularly desire
      (2.1 +/- 0.6 to 3.3 +/- 1.2, P < .0001), arousal (P < .0001), lubrication (P =
      .03), and orgasm (P = .005). CONCLUSION: In this cohort of premenopausal women
      with HSDD, 5 weeks of acupuncture therapy was associated with significant
      improvements in sexual function, particularly desire. This supports a role for
      acupuncture as a therapeutic option for women with low desire.

PMID- 27033340
TI  - Writing the history of virology in the twentieth century: Discovery, disciplines,
      and conceptual change.
AB  - Concerned with the study of viruses and the diseases they cause, virology is now
      a well-established scientific discipline. Whereas aspects of its history from the
      late nineteenth to the mid-twentieth century have often been recounted through a
      number of detailed case studies, few general discussions of the historiography of
      virology have been offered. Looking at the ways in which the history of virology
      has been told, this article examines a number of debates among scientists and
      historians of biology and show how they are based on a different understanding of
      notions such as "discipline", of processes such as "scientific discovery" as well
      as on distinct views about what the history of science is and how it should be
      written (the opposition between "longue duree" and "micro-history" or between
      history of "concepts" versus "experimental methods"). The analysis provided here
      also suggests that a richer historiography of virology will require looking at
      the variations over time of the relations between conceptual, technological, and
      institutional factors that fostered its development at the intersection of
      several other scientific fields in the life sciences. 

PMID- 27033341
TI  - Effect of flecainide on suppression of ventricular fibrillation in a patient with
      early repolarization syndrome.

PMID- 27033342
TI  - Effect of suboptimal anticoagulation treatment with antiplatelet therapy and
      warfarin on clinical outcomes in patients with nonvalvular atrial fibrillation: A
      population-wide cohort study.
AB  - BACKGROUND: The actual consequence of suboptimal anticoagulation management in
      patients with nonvalvular atrial fibrillation (NVAF) is unclear in the real-life
      practice. OBJECTIVE: The purpose of this study was to identify the prevalence of
      suboptimally anticoagulated patients with NVAF and compare the effectiveness and
      safety of antiplatelet drugs with warfarin. METHODS: We performed a retrospective
      cohort study using a population-wide database managed by the Hong Kong Hospital
      Authority. Patients newly diagnosed with NVAF during 2010-2013 were included in
      the analysis. A Cox proportional hazards regression model with 1:1 propensity
      score matching was used to compare the risk of ischemic stroke, intracranial
      hemorrhage, gastrointestinal bleeding, and all-cause mortality between patients
      receiving antiplatelet drugs and those receiving warfarin stratified by level of
      international normalized ratio (INR) control. RESULTS: Of the 35,551 patients
      with NVAF, 30,294 (85.2%) had a CHA2DS2-VASc (congestive heart failure,
      hypertension, age >=75 years [doubled], diabetes mellitus, age 65-74 years, prior
      stroke/transient ischemic attack [doubled], vascular disease, and sex category
      [female]) score of >=2 (target group for anticoagulation). Of these, 7029 (23.2%)
      received oral anticoagulants and 18,508 (61.1%) received antiplatelet drugs
      alone. There were 1541 (67.7%) of warfarin users who had poor INR control (time
      in therapeutic range [2.0-3.0] <60%). Patients receiving warfarin had comparable
      risks of intracranial hemorrhage (hazard ratio [HR] 1.24; 95% confidence interval
      [CI] 0.65-2.34) and gastrointestinal bleeding (HR 1.23; 95% CI 0.84-1.81) and
      lower risk of ischemic stroke (HR 0.40; 95% CI 0.28-0.57) and all-cause mortality
      (HR 0.45; 95% CI 0.36-0.57) than did patients receiving antiplatelet drugs alone.
      Good INR control was associated with a reduced risk of ischemic stroke (HR 0.48;
      95% CI 0.27-0.86) as compared with poor INR control. Modeling analyses suggested
      that ~40,000 stroke cases could be potentially prevented per year in the Chinese
      population if patients were optimally treated. CONCLUSION: More than three
      quarters of high-risk patients among this Chinese population with NVAF were not
      anticoagulated or had poor INR control. There is an urgent need to improve the
      optimization of anticoagulation for stroke prevention in patients with atrial
      fibrillation.

PMID- 27033343
TI  - Optimization of cold-adapted alpha-galactosidase expression in Escherichia coli.
AB  - alpha-Galactosidase (alpha-PsGal) of the cold-adapted marine bacterium
      Pseudoalteromonas sp. KMM 701 was cloned into the pET-40b(+) vector to study its
      properties and to develop an effective method for modifying human B-erythrocytes
      into O-blood group. The use of heat-shock as a pre-induction treatment, IPTG
      concentration of 0.2 mM and post-induction cultivation at 18  degrees C for 20 h
      in the developed MX-medium allowed increasing the recombinant Escherichia coli
      Rosetta (DE3)/40Gal strain productivity up to 30 times and the total soluble
      alpha-PsGal yield up to 40 times.

PMID- 27033344
TI  - MDCT evaluation of acute aortic syndrome (AAS).
AB  - Non-traumatic acute thoracic aortic syndromes (AAS) describe a spectrum of life
      threatening aortic pathologies with significant implications on diagnosis,
      therapy and management. There is a common pathway for the various manifestations
      of AAS that eventually leads to a breakdown of the aortic intima and media.
      Improvements in biology and health policy and diffusion of technology into the
      community resulted in an associated decrease in mortality and morbidity related
      to aortic therapeutic interventions. Hybrid procedures, branched and fenestrated
      endografts, and percutaneous aortic valves have emerged as potent and viable
      alternatives to traditional surgeries. In this context, current state-of-the art
      multidetector CT (MDCT) is actually the gold standard in the emergency setting
      because of its intrinsic diagnostic value. Management of acute aortic disease has
      changed with the increasing realization that endovascular therapies may offer
      distinct advantages in these situations. This article provides a summary of AAS,
      focusing especially on the MDCT technique, typical and atypical findings and
      common pitfalls of AAS, as well as recent concepts regarding the subtypes of AAS,
      consisting of aortic dissection, intramural haematoma, penetrating
      atherosclerotic ulcer and unstable aortic aneurysm or contained aortic rupture.
      MDCT findings will be related to pathophysiology, timing and management options
      to achieve a definite and timely diagnostic and therapeutic definition. In the
      present article, we review the aetiology, pathophysiology, clinical presentation,
      outcomes and therapeutic approaches to acute aortic syndromes. 

PMID- 27033346
TI  - Effects of a kindergarten-based, family-involved intervention on motor
      performance ability in 3- to 6-year-old children: the ToyBox-study.
AB  - : This study targeted to examine the effect of the ToyBox-intervention, a
      kindergarten-based, family-involved intervention, aiming to improve preschooler's
      energy-related behaviours (e.g., physical activity) on motor performance ability.
      Physical activity sessions, classroom activities, environmental changes and tools
      for parents were the components of the 1-year intervention. The intervention and
      control were cluster-randomised, and children's anthropometry and two motor test
      items (jumping from side to side, JSS and standing long jump, SLJ) were assessed.
      A total of 1293 (4.6 +/- 0.69 years; 52% boys) from 45 kindergartens in Germany
      were included (intervention, n = 863; control, n = 430). The effect was assessed
      using generalised estimating equation. The intervention group showed a better
      improvement in JSS (Estimate 2.19 jumps, P = 0.01) and tended to improve better
      in SLJ (Estimate 2.73 cm, P = 0.08). The intervention was more effective in boys
      with respect to SLJ (P of interaction effect = 0.01). Children aged <4.5 years
      did not show a significant benefit while older children improved (JSS, Estimate
      3.38 jumps, P = 0.004; SLJ, Estimate 4.18 cm, P = 0.04). Children with low socio
      economic status improved in JSS (Estimate 5.98 jumps, P = 0.0001). The ToyBox
      intervention offers an effective strategy to improve specific components of motor
      performance ability in early childhood. Future programmes should consider
      additional strategies specifically targeting girls and younger aged children.
      ABBREVIATIONS: BMI: body mass index; SES: socio-economic status; JSS: jumping
      from side to side; SLJ: standing long jump; SD: standard deviation; GEE:
      generalised estimating equation.

PMID- 27033345
TI  - Awake behaving electrophysiological correlates of forelimb hyperreflexia,
      weakness and disrupted muscular synchronization following cervical spinal cord
      injury in the rat.
AB  - Spinal cord injury usually occurs at the level of the cervical spine and results
      in profound impairment of forelimb function. In this study, we recorded awake
      behaving intramuscular electromyography (EMG) from the biceps and triceps muscles
      of the impaired forelimb during volitional and reflexive forelimb movements
      before and after unilateral cervical spinal cord injury (cSCI) in rats. C5/C6
      hemicontusion reduced volitional forelimb strength by more than 50% despite
      weekly rehabilitation for one month post-injury. Triceps EMG during volitional
      strength assessment was reduced by more than 60% following injury, indicating
      reduced descending drive. Biceps EMG during reflexive withdrawal from a thermal
      stimulus was increased by 500% following injury, indicating flexor withdrawal
      hyperreflexia. The reduction in volitional forelimb strength was significantly
      correlated with volitional and reflexive biceps EMG activity. Our results support
      the hypothesis that biceps hyperreflexia and descending volitional drive both
      significantly contribute to forelimb strength deficits after cSCI and provide new
      insight into dynamic muscular dysfunction after cSCI. The use of multiple
      automated quantitative measures of forelimb dysfunction in the rodent cSCI model
      will likely aid the search for effective regenerative, pharmacological, and
      neuroprosthetic treatments for spinal cord injury.

PMID- 27033347
TI  - 4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted
      Selective Plane Illumination Microscopy (2PE-iSPIM).
AB  - In the last decade light sheet fluorescence microscopy techniques, such as
      selective plane illumination microscopy (SPIM), has become a well established
      method for developmental biology. However, conventional SPIM architectures hardly
      permit imaging of certain tissues since the common sample mounting procedure,
      based on gel embedding, could interfere with the sample morphology. In this work
      we propose an inverted selective plane microscopy system (iSPIM), based on non
      linear excitation, suitable for 3D tissue imaging. First, the iSPIM architecture
      provides flexibility on the sample mounting, getting rid of the gel-based
      mounting typical of conventional SPIM, permitting 3D imaging of hippocampal
      slices from mouse brain. Moreover, all the advantages brought by two photon
      excitation (2PE) in terms of reduction of scattering effects and contrast
      improvement are exploited, demonstrating an improved image quality and contrast
      compared to single photon excitation. The system proposed represents an optimal
      platform for tissue imaging and it smooths the way to the applicability of light
      sheet microscopy to a wider range of samples including those that have to be
      mounted on non-transparent surfaces. 

PMID- 27033348
TI  - SIS Epidemic Propagation on Hypergraphs.
AB  - Mathematical modelling of epidemic propagation on networks is extended to
      hypergraphs in order to account for both the community structure and the
      nonlinear dependence of the infection pressure on the number of infected
      neighbours. The exact master equations of the propagation process are derived for
      an arbitrary hypergraph given by its incidence matrix. Based on these, moment
      closure approximation and mean-field models are introduced and compared to
      individual-based stochastic simulations. The simulation algorithm, developed for
      networks, is extended to hypergraphs. The effects of hypergraph structure and the
      model parameters are investigated via individual-based simulation results.

PMID- 27033349
TI  - Liposomes as Delivery System of a Sn(IV) Complex for Cancer Therapy.
AB  - PROPOSE: Tin complexes demonstrate antiproliferative activities in some case
      higher than cisplatin, with IC50 at the low micromolar range. We have previously
      showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic
      oximehydroxamic acid group [nBu2Sn(L)]3 (L=N,2-dihydroxy-5-[N
      hydroxyethanimidoyl]benzamide) (MG85) shows high anti-proliferative activity,
      induces apoptosis and oxidative stress, and causes destabilization of tubulin
      microtubules, particularly in colorectal carcinoma cells. Despite the great
      efficacy towards cancer cells, this complex still shows some cytotoxicity to
      healthy cells. Targeted delivery of this complex specifically towards cancer
      cells might foster cancer treatment. METHODS: MG85 complex was encapsulated into
      liposomal formulation with and without an active targeting moiety and cancer and
      healthy cells cytotoxicity was evaluated. RESULTS: Encapsulation of MG85 complex
      in targeting PEGylated liposomes enhanced colorectal carcinoma (HCT116) cancer
      cell death when compared to free complex, whilst decreasing cytotoxicity in non
      tumor cells. Labeling of liposomes with Rhodamine allowed assessing
      internalization in cells, which showed significant cell uptake after 6 h of
      incubation. Cetuximab was used as targeting moiety in the PEGylated liposomes
      that displayed higher internalization rate in HCT116 cells when compared with non
      targeted liposomes, which seems to internalize via active binding of Cetuximab to
      cells. CONCLUSIONS: The proposed formulation open new avenues in the design of
      innovative transition metal-based vectorization systems that may be further
      extended to other novel metal complexes towards the improvement of their anti
      cancer efficacy, which is usually hampered by solubility issues and/or toxicity
      to healthy tissues.

PMID- 27033350
TI  - Prevalence of Drug Resistance Associated Mutations Among the Anti Retroviral
      Therapy Exposed HIV-1 Infected Individuals in Manipur, Northeast India.
AB  - BACKGROUND: Manipur is one of the highest HIV prevalence states of India because
      of its geographical location at the international border near the golden triangle
      of South-East Asia, but no study on drug resistance associated mutations (DRAMs)
      has been reported yet. OBJECTIVE: A population-based study on DRAMs of HIV-1
      among the anti-retroviral therapy (ART) exposed HIV-1 infected individuals of
      Manipur was conducted. METHODS: 110 HIV-1 positive individuals who had initially
      exposed to first line anti-HIV drugs were recruited for the surveillance of
      DRAMs. Reverse transcriptase and protease genes of HIV-1 were amplified,
      sequenced and analyzed. RESULTS: Significant prevalence of DRAMs of HIV-1 was
      found among the ART exposed HIV-1 infected individuals of Manipur. The results
      revealed that 37%, 29% and 7% individuals harbor HIV-1 strains mutated at the
      target sites of nonnucleoside reverse transcriptase inhibitors, nucleoside
      reverse transcriptase inhibitors and protease inhibitors respectively.
      Predominant DRAMs at RT genes were M184V, T215Y, M41L and V108I and H221Y while
      at PR genes were M46I and I47V. Among the high risk groups, intravenous drug
      users have the highest number of DRAMs followed by heterosexual individuals.
      Analysis of viral subtype based on pol gene revealed 83% subtype C, 11.8%
      recombinant forms and 5.2% subtype B. CONCLUSION: DRAMs at the target sites of
      reverse transcriptase inhibitors are high and these were found to have developed
      resistance to the primary ART drugs that are used in Manipur. The findings of
      this study will help the clinicians to guide patients during the course of ART
      treatment regimes.

PMID- 27033351
TI  - Guiding coronary revascularization using PET stress myocardial perfusion imaging:
      The proof is in the pudding.

PMID- 27033352
TI  - Dose reduction in half-time myocardial perfusion SPECT-CT with multifocal
      collimation.
AB  - BACKGROUND: Recent technological advances in myocardial perfusion imaging may
      warrant the use of lower injected activity. We evaluated whether quantitative
      measures of stress myocardial perfusion defects using Tc-99m sestamibi and low
      energy high-resolution (LEHR) collimators are equivalent to lower dose SPECT-CT
      with cardiac multifocal collimators and software (IQ.SPECT). METHODS: 93 patients
      underwent one-day rest-stress gated SPECT-CT. Following conventional rest
      imaging, 925-1100 MBq (25-30 mCi) of Tc-99m sestamibi was injected during stress
      testing. Stress SPECT-CT images were acquired two ways: with LEHR (13 minutes)
      and IQ.SPECT (7 minutes). Low-dose IQ.SPECT stress was simulated by subsampling
      the full-dose data to half-, quarter-, and eighth-count levels. Abnormalities
      were quantified using the total perfusion deficit (TPD) score and dose-specific
      databases. RESULTS: The mean +/- SD of the differences between LEHR and IQ.SPECT
      TPD scores were -1.01 +/- 5.36%, -0.10 +/- 5.81%, 1.78 +/- 4.81%, and 1.75 +/-
      6.05% at full, half, quarter, and eighth doses, respectively. Differences were
      statistically significant for quarter and eighth doses. Correlation between LEHR
      and IQ.SPECT was excellent at all doses (R >= 0.93). Bland-Altman plots
      demonstrated minimal bias. CONCLUSIONS: With IQ.SPECT, quantitative stress SPECT
      CT imaging is possible with half of the standard injected activity in half the
      time.

PMID- 27033353
TI  - A naturalistic examination of negative affect and disorder-related rumination in
      anorexia nervosa.
AB  - In anorexia nervosa (AN), volitional inhibition of rewarding behaviors, such as
      eating, involves a conflict between the desire to suppress appetite and the
      inherent motive to consume. This conflict is thought to have costs that carry
      over into daily life, e.g., triggering negative affect and/or recurring
      ruminations, which may ultimately impact long term outcome. Hence, increasing
      research effort is being dedicated to understand the link between emotional and
      ruminative processes in the etiology and maintenance of AN. We investigated
      whether affective states influence disorder-related rumination in AN applying
      "ecological momentary assessment", a method which allows the experimenter to gain
      insight into psychological processes in the natural environment and assess data
      in real time. Participants (AN = 37, healthy controls = 33) were given a
      smartphone for 14 days. A ringtone signaled at six random time-points each day to
      fill in a questionnaire, which gauged disorder-typical thoughts about food and
      weight as well as affective state. Analyses, applying hierarchical linear models
      confirmed that AN patients spend more time thinking about food, body shape and
      weight than controls (p < 0.001). Additionally, the results support the
      hypothesis that momentary negative affect (but not baseline depression (p = 0.56)
      or anxiety symptoms (p = 0.60) are positively associated with a higher amount of
      disorder-related rumination in patients (p < 0.001). Our findings are in line
      with theories which claim that ruminative thinking induces a vulnerability to
      negative stimuli which, in turn, fosters heightened negative affect. Thus,
      therapeutic interventions could be improved by implementing modules that
      specifically target disorder-related rumination.

PMID- 27033354
TI  - Difference between the vocalizations of two sister species of pigeons explained
      in dynamical terms.
AB  - Vocal communication is an unique example, where the nonlinear nature of the
      periphery can give rise to complex sounds even when driven by simple neural
      instructions. In this work we studied the case of two close-related bird species,
      Patagioenas maculosa and Patagioenas picazuro, whose vocalizations differ only in
      the timbre. The temporal modulation of the fundamental frequency is similar in
      both cases, differing only in the existence of sidebands around the fundamental
      frequency in the P. maculosa. We tested the hypothesis that the qualitative
      difference between these vocalizations lies in the nonlinear nature of the
      syrinx. In particular, we propose that the roughness of maculosa's vocalizations
      is due to an asymmetry between the right and left vibratory membranes, whose
      nonlinear dynamics generate the sound. To test the hypothesis, we generated a
      biomechanical model for vocal production with an asymmetric parameter Q with
      which we can control the level of asymmetry between these membranes. Using this
      model we generated synthetic vocalizations with the principal acoustic features
      of both species. In addition, we confirmed the anatomical predictions by making
      post mortem inspection of the syrinxes, showing that the species with tonal song
      (picazuro) has a more symmetrical pair of membranes compared to maculosa.

PMID- 27033355
TI  - Interaction with gravitropism, reversibility and lateral movements of
      phototropically stimulated potato shoots.
AB  - Phototropic (PT) and gravitropic (GT) bending are the two major tropic movements
      that determine the spatial position of potato shoots. We studied PT bending of
      potato plantlets grown under long-day photoperiods in several prearranged
      position setups providing different interactions with the GT response. Starting
      with the standard PT stimulation setup composed of unilateral irradiation of
      vertically positioned shoots, experiments were also done in antagonistic and
      synergistic setups and in treatments with horizontal displacement of the light
      source. In the standard setup, PT bending suppressed the GT bending, which could
      occur only if the PT stimulation was cancelled. The antagonistic position, with
      phototropism and gravitropism attempting to bend shoots in opposite directions,
      showed phototropism and gravitropism as independent bending events with the
      outcome varying throughout the day reflecting diurnal changes in the competence
      of individual tropic components. Whilst gravitropism was constant, phototropism
      had a marked daily fluctuation of its magnitude with a prominent morning maximum
      starting an hour after the dawn in the growth room and lasting for the next 6 h.
      When phototropism and gravitropism were aligned in a synergistic position,
      stimulating shoot bending in the same direction, there was little quantitative
      addition of their individual effects. The long period of morning PT bending
      maximum enabled multiple PT bending events to be conducted in succession, each
      one preceded by a separate lag phase. Studies of secondary PT events showed that
      potato plantlets can follow and adjust their shoot position in response to both
      vertical and horizontal movements of a light source. PT bending was reversible,
      since the 180 degrees  horizontal change of a blue light (BL) source position
      resulted in reversal of bending direction after a 20-min-long lag phase. 

PMID- 27033357
TI  - Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental
      ENU-induced gliomas.
AB  - Nestin+cells from spheroid aggregates display typical histopathological features
      compatible with cell stemness. Nestin and CD133+cells found in glioblastomas,
      distributed frequently around aberrant vessels, are considered as potential
      cancer stem cells. They are possible targets for antitumoral therapy because they
      lead the tumorigenesis, invasiveness and angiogenesis. However, little is known
      about their role and presence in low-grade gliomas. The aim of this work is to
      localize and characterize the distribution of these cells inside tumors during
      the development of experimental endogenous glioma. For this study, a single dose
      of Ethyl-nitrosourea was injected into pregnant rats. Double immunofluorescences
      were performed in order to identify stem-like and differentiated cells. Low-grade
      gliomas display Nestin+cells distributed throughout the tumor. More malignant
      gliomas show, in addition to that, a perivascular location with some Nestin+cells
      co-expressing CD133 or VEGF, and the intratumoral spheroid aggregates of
      Nestin/CD133+cells. These structures are encapsulated by well-differentiated
      VEGF/GFAP+cells. Spheroid aggregates increase in size in the most malignant
      stages. Spheroid aggregates have morphological and phenotypic similarities to in
      vitro neurospheres and could be an in vivo analogue of them. These arrangements
      could be a reservoir of undifferentiated cells formed to escape adverse
      microenvironments. 

PMID- 27033356
TI  - Leaf age dependent changes in within-canopy variation in leaf functional traits:
      a meta-analysis.
AB  - Within-canopy variation in leaf structural and photosynthetic characteristics is
      a major means by which whole canopy photosynthesis is maximized at given total
      canopy nitrogen. As key acclimatory modifications, leaf nitrogen content (N A)
      and photosynthetic capacity (A A) per unit area increase with increasing light
      availability in the canopy and these increases are associated with increases in
      leaf dry mass per unit area (M A) and/or nitrogen content per dry mass and/or
      allocation. However, leaf functional characteristics change with increasing leaf
      age during leaf development and aging, but the importance of these alterations
      for within-canopy trait gradients is unknown. I conducted a meta-analysis based
      on 71 canopies that were sampled at different time periods or, in evergreens,
      included measurements for different-aged leaves to understand how within-canopy
      variations in leaf traits (trait plasticity) depend on leaf age. The analysis
      demonstrated that in evergreen woody species, M A and N A plasticity decreased
      with increasing leaf age, but the change in A A plasticity was less suggesting a
      certain re-acclimation of A A to altered light. In deciduous woody species, M A
      and N A gradients in flush-type species increased during leaf development and
      were almost invariable through the rest of the season, while in continuously leaf
      forming species, the trait gradients increased constantly with increasing leaf
      age. In forbs, N A plasticity increased, while in grasses, N A plasticity
      decreased with increasing leaf age, reflecting life form differences in age
      dependent changes in light availability and in nitrogen resorption for growth of
      generative organs. Although more work is needed to improve the coverage of age
      dependent plasticity changes in some plant life forms, I argue that the age
      dependent variation in trait plasticity uncovered in this study is large enough
      to warrant incorporation in simulations of canopy photosynthesis through the
      growing period. 

PMID- 27033358
TI  - Clinical experience with contact-force and flexible-tip ablation catheter
      designs.
AB  - PURPOSE: Lesion formation is a critical determinant of technical and clinical
      success of pulmonary vein isolation. Different catheter designs aim to enhance
      tissue contact during ablation to enable optimized lesion formation. We analyzed
      procedural characteristics and predictors of clinical success in patients ablated
      with three different contemporary ablation catheters. METHODS: Two hundred sixty
      eight sequentially included patients receiving pulmonary vein isolation (PVI)
      with conventional (n = 122), contact-force (n = 96) and flexible-tip (n = 60)
      catheters were followed for a median of 14.1 months with 7d-Holter-monitoring and
      TTE at 3, 6, 12, and 24 months. Baseline characteristics and follow-up times were
      homogeneous across all groups. RESULTS: Multivariable Cox proportional hazard
      regression for arrhythmia recurrence demonstrated a favorable hazard ratio for
      contact-force and flexible-tip catheters vs. conventional open irrigation
      catheters. Procedure time and fluoroscopy time were shorter for contact-force and
      flexible-tip catheters versus conventional catheters, but equal between. Linear
      lesions were applied in 58 % of contact-force and 66 % of flexible-tip cases, and
      CFAEs were targeted in 26 % of either. CONCLUSIONS: Our non-randomized
      prospectively collected data do not show a difference in observed procedure
      characteristics and in clinical outcome for flexible-tip versus contact-force
      catheter designs, while both display improved performance against conventional
      open irrigated-tip catheters. Linear lesions and CFAEs ablation were not
      associated with improved arrhythmia-free survival.

PMID- 27033359
TI  - Lipid-Based Liquid Crystals As Carriers for Antimicrobial Peptides: Phase
      Behavior and Antimicrobial Effect.
AB  - The number of antibiotic-resistant bacteria is increasing worldwide, and the
      demand for novel antimicrobials is constantly growing. Antimicrobial peptides
      (AMPs) could be an important part of future treatment strategies of various
      bacterial infection diseases. However, AMPs have relatively low stability,
      because of proteolytic and chemical degradation. As a consequence, carrier
      systems protecting the AMPs are greatly needed, to achieve efficient treatments.
      In addition, the carrier system also must administrate the peptide in a
      controlled manner to match the therapeutic dose window. In this work, lyotropic
      liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water
      and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers
      for AMPs. These LC structures have the capability of solubilizing both
      hydrophilic and hydrophobic substances, as well as being biocompatible and
      biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes
      and hexosomes) have been studied. Three AMPs have been investigated with respect
      to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060,
      and LL-37. Characterization of the LC structures was performed using small-angle
      X-ray scattering (SAXS), dynamic light scattering, zeta-potential, and cryogenic
      transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra
      performance liquid chromatography. The antimicrobial effect of the LCNPs was
      investigated in vitro using minimum inhibitory concentration (MIC) and time-kill
      assay. The most hydrophobic peptide (AP114) was shown to induce an increase in
      negative curvature of the cubic LC system. The most polar peptide (DPK-060)
      induced a decrease in negative curvature while LL-37 did not change the LC phase
      at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover,
      cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial
      activity, whereas particles loaded with peptide LL-37 displayed a loss in its
      broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction
      in antimicrobial activity.

PMID- 27033361
TI  - [(18)F]FE@SNAP-a specific PET tracer for melanin-concentrating hormone receptor 1
      imaging?
AB  - BACKGROUND: The melanin-concentrating hormone receptor 1 (MCHR1), which is highly
      expressed in the lateral hypothalamus, plays a key role in energy homeostasis,
      obesity and other endocrine diseases. Hence, there is a major interest in in vivo
      imaging of this receptor. A PET tracer would allow non-invasive in vivo
      visualization and quantification of the MCHR1. The aim of the study was the ex
      vivo evaluation of the MCHR1 ligand [(18)F]FE@SNAP as a potential PET tracer for
      the MCHR1. METHODS: [(18)F]FE@SNAP was injected directly into the jugular vein of
      awake naive rats for ex vivo brain autoradiography, biodistribution and
      additional blood metabolite analysis. Blocking experiments were conducted using
      the unlabeled MCHR1 ligand SNAP-7941. RESULTS: A high uptake of [(18)F]FE@SNAP
      was observed in the lateral hypothalamus and the ventricular system. Both regions
      were significantly blocked by SNAP-7941. Biodistribution evinced the highest
      uptake in the kidneys, adrenals, lung and duodenum. Specific blocking with SNAP
      7941 led to a significant tracer reduction in the heart and adrenals. In plasma
      samples, 47.73 +/- 6.1 % of a hydrophilic radioactive metabolite was found 45 min
      after tracer injection. CONCLUSIONS: Since [(18)F]FE@SNAP uptake was
      significantly blocked in the lateral hypothalamus, there is strong evidence that
      [(18)F]FE@SNAP is a highly suitable agent for specific MCHR1 imaging in the
      central nervous system. Additionally, this finding is supported by the specific
      blocking in the ventricular system, where the MCHR1 is expressed in the ependymal
      cells. These findings suggest that [(18)F]FE@SNAP could serve as a useful imaging
      and therapy monitoring tool for MCHR1-related pathologies.

PMID- 27033360
TI  - Neuro-protective Mechanisms of Lycium barbarum.
AB  - Neuronal diseases, including retinal disorders, stroke, Alzheimer's disease,
      Parkinson's disease and spinal cord injury, affect a large number of people
      worldwide and cause heavy social and economic burdens. Although many efforts have
      been made by scientists and clinicians to develop novel drug and healthcare
      strategies, few of them received satisfactory outcomes to date. Lycium barbarum
      is a traditional homology of medicine and food in Chinese medicine, with the
      capability to nourish the eyes, liver and kidneys. Recent studies have also
      explored its powerful neuro-protective effects on a number of neuronal diseases.
      In the current review, we collected key recent findings regarding the neuro
      protective effects and mechanisms of L. barbarum derivatives, primarily its
      polysaccharide (LBP) , in some common diseases of the nervous system. A
      comprehensive comparison with currently available drugs has also been discussed.
      In general, LBP is a promising neuronal protector with potent ameliorative
      effects on key pathological events, such as oxidative stress, inflammation,
      apoptosis and cell death with minimal side effects. 

PMID- 27033362
TI  - Yeast-containing feed additive alters gene expression profiles associated with
      innate immunity in whole blood of a rodent model.
AB  - Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses
      in ruminant livestock and reduces subsequent production losses. The objective was
      to identify molecular pathways by which dietary YCA may modify immune responses
      using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet
      containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7
      (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group)
      d. At the end of the feeding periods, whole blood was collected and the isolated
      RNA was analyzed for the expression of 84 genes involved in innate and cell
      mediated adaptive immune responses. Three bacterial pattern recognition receptors
      TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%:
      + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33)
      and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%:
      +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates.
      In conclusion, feeding YCA may potentially increase recognition and responses to
      bacterial pathogens and T-cell activation and differentiation and thereby
      maintain health and prevent production losses.

PMID- 27033365
TI  - Assessing the place of nicotine vaporisers in tobacco control.

PMID- 27033364
TI  - Replacing risk-based early-onset-disease prevention with intrapartum group B
      streptococcus PCR testing.
AB  - OBJECTIVE: To evaluate the effect of a rapid PCR-based group B streptococcus
      (GBS) test on length of stay in hospital among newborns, antibiotic use, and GBS
      early-onset-disease (EOD) incidence. METHODS: We conducted a before and after
      service evaluation including term deliveries between 1st January and 12th
      November 2014 (6688 deliveries). Length of stay in the hospital, GBS-EOD
      incidence and antibiotic use were evaluated. RESULTS: We recorded three confirmed
      and 74 possible cases of GBS-EOD in Phase 1, and 85 possible cases in Phase 2. In
      newborns with suspected infection, the introduction of the rapid test was related
      to a decreased length of stay on the pediatric care unit by 1.16 days (p = 0.01),
      and an increase in the length of stay on the mother-and-baby ward by 1.11 days (p
      < 0.001). No increase in antibiotics was noted. CONCLUSION: The introduction of a
      point of care test was associated with a reduction in length of stay in the
      pediatric care unit, without an increase in antibiotic use. This test could
      improve the accuracy of GBS colonization detection, and help to prevent
      intrapartum transmission as no verified GBS-EOD cases were recorded with the
      intrapartum PCR algorithm.

PMID- 27033366
TI  - Use of traditional medicine in middle-income countries: a WHO-SAGE study.
AB  - It is frequently stated in the scientific literature, official reports and the
      press that 80% of Asian and African populations use traditional medicine (TM) to
      meet their healthcare needs; however, this statistic was first reported in 1983.
      This study aimed to update knowledge of the prevalence of TM use and the
      characteristics of those who access it, to inform health policy-makers as
      countries seek to fulfil the WHO TM strategy 2014-23 and harness TM for
      population health. Prevalence of reported use of TM was studied in 35 334
      participants of the WHO-SAGE, surveyed 2007-10. TM users were compared with users
      of modern healthcare in univariate and multivariate analyses. Characteristics
      examined included age, sex, geography (urban/rural), income quintile, education,
      self-reported health and presence of specific chronic conditions. This study
      found TM use was highest in India, 11.7% of people reported that their most
      frequent source of care during the previous 3 years was TM; 19.0% reported TM use
      in the previous 12 months. In contrast <3% reported TM as their most frequent
      source of care in China, Ghana, Mexico, Russia and South Africa; and <2% reported
      using TM in the previous year in Ghana, Mexico, Russia and South Africa. In
      univariate analyses, poorer, less educated and rural participants were more
      likely to be TM-users. In the China multivariate analysis, rurality, poor self
      reported health and presence of arthritis were associated with TM use; whereas
      diagnosed diabetes, hypertension and cataracts were less prevalent in TM users.
      In Ghana and India, lower income, depression and hypertension were associated
      with TM use. In conclusion, TM use is less frequent than commonly reported. It
      may be unnecessary, and perhaps futile, to seek to employ TM for population
      health needs when populations are increasingly using modern medicine. 

PMID- 27033363
TI  - Association of Reactive-Proactive Aggression and Anxiety Sensitivity with
      Internalizing and Externalizing Symptoms in Children with Attention
      Deficit/Hyperactivity Disorder.
AB  - This study evaluates the associations among the symptoms of anxiety, depression,
      and disruptive behavioral disorders (DBD) in the context of their relationships
      with reactive-proactive aggression and anxiety sensitivity in children with
      attention-deficit/hyperactivity disorder (ADHD). The sample consisted of 342
      treatment-naive children with ADHD. The severity of ADHD and DBD symptoms were
      assessed via parent- and teacher-rated inventories. Anxiety sensitivity, reactive
      proactive aggression and severity of anxiety and depression symptoms of children
      were evaluated by self-report inventories. According to structural equation
      modeling, depression and anxiety scores had a relation with the DBD scores
      through reactive-proactive aggression. Results also showed a negative relation of
      the total scores of anxiety sensitivity on DBD scores, while conduct disorder
      scores had a positive relation with anxiety scores. This study suggests that
      examining the relations of reactive-proactive aggression and anxiety sensitivity
      with internalizing and externalizing disorders could be useful for understanding
      the link among these disorders in ADHD.

PMID- 27033367
TI  - A mixed-method outcome evaluation of a specialist Alcohol Hospital Liaison Team.
AB  - AIMS: To evaluate the effectiveness of an Alcohol Hospital Liaison Team at
      reducing alcohol-specific hospital attendances and admissions. METHODS: In a
      mixed-method evaluation, 96 patients who accessed the team were monitored using
      data for alcohol-specific hospital attendances and Accident and Emergency (A&E)
      admissions before, during, and after engaging with the team. A feedback survey
      was sent to patients and a focus group was held with staff from the team to
      identify barriers and facilitators to the successful delivery of this service.
      RESULTS: No differences were observed when looking at alcohol admissions or A&E
      attendances before patients engaged with the service to those after discharge.
      While hospital admissions decreased slightly and A&E attendances increased
      slightly, these differences were not significant. Hospital admissions and A&E
      attendances increased significantly during engagement with the service. The focus
      group identified confusion over who should be delivering brief interventions and
      that the team was holding onto patients for too long. CONCLUSION: The results of
      this evaluation demonstrated that this team was not effective at reducing alcohol
      attendances or admissions due to a number of factors. Policy makers should make
      note of the barriers to effectiveness highlighted in this article, before
      commissioning alcohol care teams in the future.

PMID- 27033368
TI  - Erratum to: A hydrodynamic view of the first-passage folding of Trp-cage
      miniprotein.

PMID- 27033369
TI  - Classic Spotlight: Dynamics of the Bacterial Cytoplasm.

PMID- 27033370
TI  - Classic Spotlight: Discovery of ftsZ.

PMID- 27033373
TI  - DNA cytophotometric and histological analysis of N-butyl-N-(4
      hydroxybutyl)nitrosamine-induced precancerous lesions of the bladder urothelium.
AB  - PURPOSE: The morphology of experimentally induced urinary bladder precancerous
      lesions has been differentially interpreted in the literature. Here, we aimed to
      describe the development of precancerous lesions of the urothelium histologically
      and by DNA cytophotometric analysis. METHODS: We induced precancerous lesions of
      the urothelium in 60 Wistar rats with 0.05 % N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN) solution as drinking water. After exposure for 2
      20 weeks, each animal received tap water for 2 weeks. Subsequently, six animals
      were killed every 2 weeks, and urothelia of three urinary bladders per time point
      were examined by DNA cytophotometry of smear preparations. An additional three
      urinary bladders were processed for histological analysis. RESULTS: Over 20
      weeks, BBN exposure led to a significant difference between the control group and
      most of the BBN-exposed 2-week groups and to differences between most of these
      time point groups. After week 4, this difference included a higher proportion of
      cells with increased nuclear DNA content. At the end of the experiment, DNA
      cytophotometric values of the urothelium in experimental rats corresponded to
      those of poorly differentiated urothelial carcinomas. CONCLUSIONS: Biologically
      significant stages of precancerous lesions were already detectable after 4 weeks
      of BBN exposure, considerably earlier than previously described in the
      literature.

PMID- 27033374
TI  - Safety of vaginal microbial transfer in infants delivered by caesarean, and
      expected health outcomes.

PMID- 27033375
TI  - [Emergencies of the external genital area].
AB  - BACKGROUND: In addition to epididymitis and testicular torsion, emergencies of
      the external genital are rare. Rapid diagnosis and therapy are essential so that
      immediate therapy can be provided, which is important for survival (Fournier
      gangrene) of the patient or for the preservation of erectile function (priapism
      and penile fracture). A detailed patient history and clinical examination are
      generally sufficient for correct diagnosis. RESULTS: Under certain circumstances,
      it might be useful to perform ultrasound, computed tomography scan or magnetic
      resonance imaging or retrograde urethrography. A urine analysis is obligatory. In
      case of penetrating injuries and genital trauma in females, additional imaging
      should be performed because these are often associated with concomitant injuries
      of the rectum, vagina, or bladder. Special cases are gunshot wounds, in which
      caliber and type of weapon play an important role for the degree of damage, and
      animal or human bites. For animal bites, the risk for rabies infection and in
      case of a human bite the risk for transmission of HIV and hepatitis should be
      taken into consideration and post-exposure prophylaxis should possibly be
      offered.

PMID- 27033377
TI  - Can microbiota research change our understanding of neurodegenerative diseases?

PMID- 27033376
TI  - Limb-girdle muscular dystrophies - international collaborations for translational
      research.
AB  - The limb-girdle muscular dystrophies (LGMDs) are a diverse group of genetic
      neuromuscular conditions that usually manifest in the proximal muscles of the hip
      and shoulder girdles. Since the identification of the first gene associated with
      the phenotype in 1994, an extensive body of research has identified the genetic
      defects responsible for over 30 LGMD subtypes, revealed an increasingly varied
      phenotypic spectrum, and exposed the need to move towards a systems-based
      understanding of the molecular pathways affected. New sequencing technologies,
      including whole-exome and whole-genome sequencing, are continuing to expand the
      range of genes and phenotypes associated with the LGMDs, and new computational
      approaches are helping clinicians to adapt to this new genomic medicine paradigm.
      However, 60 years on from the first description of LGMD, no curative therapies
      exist, and systematic exploration of the natural history is still lacking. To
      enable rapid translation of basic research to the clinic, well-phenotyped and
      genetically characterized patient cohorts are a necessity, and appropriate
      outcome measures and biomarkers must be developed through natural history
      studies. Here, we review the international collaborations that are addressing
      these translational research issues, and the lessons learned from large-scale
      LGMD sequencing programmes.

PMID- 27033378
TI  - Johann Malawana: we must maintain doctors' goodwill.

PMID- 27033379
TI  - Two cases of squamous cell carcinoma of the lower leg treated with a pasteurized
      bone graft.

PMID- 27033380
TI  - Uniform and accelerated degradation of pure iron patterned by Pt disc arrays.
AB  - Pure iron has been confirmed as a promising biodegradable metal. However, the
      degradation rate of pure iron should be accelerated to meet the clinical
      requirements. In this work, two different designs of platinum disc arrays,
      including sizes of Phi20 MUm * S5 MUm and Phi4 MUm * S4 MUm, have been coated on
      the surface of pure iron. Corrosion tests showed the platinum discs formed plenty
      of galvanic cells with the iron matrix which significantly accelerated the
      degradation of pure iron. Simultaneously, due to the designability of the shape,
      size as well as distribution of Pt discs, the degradation rate as well as
      degradation uniformity of pure iron can be effectively controlled by coating with
      platinum discs. The cytotoxicity test results unveiled that Pt discs patterned
      pure iron exhibited almost no toxicity to human umbilical vein endothelial cells,
      but a significant inhibition on proliferation of vascular smooth muscle cells. In
      addition, the hemolysis rate of Pt discs patterned pure iron was lower than 1%.
      Moreover, Pt discs also effectively reduced the number of adhered platelets. All
      these results indicated that Pt discs patterning is an effective way to
      accelerate degradation and improve biocompatibility of pure iron. 

PMID- 27033381
TI  - Aqueous reactive species induced by a surface air discharge: Heterogeneous mass
      transfer and liquid chemistry pathways.
AB  - Plasma-liquid interaction is a critical area of plasma science and a knowledge
      bottleneck for many promising applications. In this paper, the interaction
      between a surface air discharge and its downstream sample of deionized water is
      studied with a system-level computational model, which has previously reached
      good agreement with experimental results. Our computational results reveal that
      the plasma-induced aqueous species are mainly H(+), nitrate, nitrite, H2O2 and
      O3. In addition, various short-lived aqueous species are also induced, regardless
      whether they are generated in the gas phase first. The production/loss pathways
      for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm,
      of which heterogeneous mass transfer and liquid chemistry are found to play a
      dominant role. The short-lived reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an
      important precursor for short-lived ROS, and in turn OH, O2(-) and HO2 play a
      crucial role for the production of short-lived RNS. Also, heterogeneous mass
      transfer depends strongly on the air gap width, resulting in two distinct
      scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is
      significantly different in these two scenarios. 

PMID- 27033382
TI  - [Consensus on epidermal growth factor receptor gene mutation detection in non
      small cell lung carcinoma].

PMID- 27033383
TI  - [Correlation of clinicopathologic features and driver gene mutation in non-small
      cell lung cancer].
AB  - OBJECTIVE: To study the relationship between mutations of well-known driver genes
      and clinicopathologic characteristics of non-small cell lung cancers (NSCLC).
      METHODS: Scorpions amplification refractory mutation system (scorpions ARMS)
      fluorescence quantitative PCR was performed to investigate 205 driver gene
      mutation status in NSCLC in correlation with clinicopathological characteristics
      of the patients. RESULTS: Driver gene mutations were detected in 146 of 205
      (71.2%) patients with NSCLC, including 81.7%(138/169) adenocarcinomas, in which
      mutations of nine genes were found: EGFR (63.3%, 107/169), KRAS (5.9%, 10/169),
      PIK3CA (4.1%, 7/169), ALK (4.1%, 7/169), ROS1 (3.0%, 5/169), RET (3.6%, 6/169),
      HER2 (1.8%, 3/169), NRAS (0.6%, 1/169) and BRAF (0.6%, 1/169). The frequencies of
      driver gene mutations were higher in adenocarcinomas, female patients and non
      smokers (P<0.01, P=0.003, P<0.01, respectively). Driver gene mutation status
      showed no correlation with either the age or the clinical stage (P=0.281,
      P=0.490, respectively). However, EGFR mutations tended to occur in
      adenocarcinoma, female, non-smokers, and patients of >=62 years of age (P<0.01,
      P<0.01, P=0.002, P=0.012, respectively). The frequency of EGFR mutation was
      positively correlated with the tumor histology of lepidic, acinar, papillary and
      micropapillary predominant growth patterns. There was no relationship between
      EGFR mutation and the clinical stage (P=0.237). The frequency of KRAS mutation
      was higher in solid predominant and invasive mucinous adenocarcinomas (P=0.015);
      that of PIK3CA mutation was higher in patients of >=62 years of age, invasive
      mucinous adenocarcinoma and fetal adenocarcinoma (P=0.015, P=0.006,
      respectively). ALK, ROS1 or RET mutation positive NSCLC tended to occur in
      nonsmokers and have solid predominant tumors and invasive mucinous adenocarcinoma
      (P=0.012, P=0.017 respectively). The frequency of EML4-ALK mutation was higher in
      the early stage patients with solid predominant tumors and invasive mucinous
      adenocarcinomas (P=0.025, P=0.014, respectively); that of ROS1 rearrangement was
      higher in invasive mucinous adenocarcinomas (P=0.049). NRAS, BRAF and HER2 gene
      mutations were infrequent and their clinical significance remained to be
      elucidated. CONCLUSIONS: The relationship between mutations of well-known driver
      genes and clinicopathological characteristics in patients with NSCLC has
      diversity, the rate of mutations is higher in non-smoking female patients with
      adenocarcinoma.

PMID- 27033384
TI  - [Mutation status of epidermal growth factor receptor and KRAS gene in non-small
      cell lung cancers at Xuanwei regions of Yunnan Province].
AB  - OBJECTIVE: To investigate the mutation status of epidermal growth factor receptor
      (EGFR) and KRAS gene in patients with non-small cell lung cancer (NSCLC) in
      Xuanwei, Yunnan and to correlate the mutation status with clinicopathologic
      features. METHODS: Mutation status of exons 18, 19, 20 and 21 of EGFR, and codons
      12, 13 of KRAS in 63 cases of NSCLC were analyzed by gene sequencing and ARMS
      Taqman probe method. Correlation with patients' clinicopathological
      characteristics was performed. RESULTS: EGFR and KRAS mutations were present in
      55.6% (35/63) and 6.3% (4/63), respectively. EGFR gene mutations were present,
      including exon 18 G719X in 14.3% (5/35), exon 19 in 14.3% (5/35), exon 20 S768I
      and T790M in 20.0% (7/35), exon 21 L858R in 31.4% (11/35), exon 18 G719X and exon
      20 S768I double mutation in 17.1% (6/35), and exon 20 T790M and exon 21 L858R
      double mutation in 2.9% (1/35). KRAS mutations were seen in codon 12 in 3 of 4
      cases, and codon 13 in 1 of 4 cases. EGFR mutations were mutually exclusive with
      KRAS mutations. According to statistic analysis, EGFR mutations were associated
      with the histological types of NSCLC(P<0.05), but without correlation with
      patient's gender, age, smoking status and lymph node metastasis(P>0.05). KRAS
      mutations in NSCLC had no correlation with the clinical pathologic
      characteristics of the patients. CONCLUSIONS: A higher frequency of EGFR exon 18
      G719X and 20 exon S768I mutations are found in the patients in Xuanwei, Yunnan.
      EGFR mutations are associated with histologic types of NSCLC, but without
      correlation with patient's gender, age, smoking status and lymph node metastasis.
      KRAS mutation in NSCLC has no correlation with the clinicopathologic
      characteristics of the patients.

PMID- 27033385
TI  - [Large-cell lung carcinoma by the 2015 WHO classification: a clinicopathologic
      analysis of 93 cases].
AB  - OBJECTIVE: To analyze the clinicopathologic characteristics of large-cell lung
      carcinoma (LCC) subtypes according to the 2015 WHO classification. METHODS: A
      total of 93 cases of LCC were identified among 1 634 cases of morphologically
      undifferentiated non-small cell lung carcinoma. Clinicopathologic and
      immunohistochemical characteristics were retrospectively reviewed. RESULTS: Among
      93 cases of LCC, 50 cases were solid adenocarcinoma (53.8%), 21 cases were non
      keratinzing squamous cell carcinoma (22.6%), 3 cases were adenosquamous carcinoma
      (3.2%), 8 cases were large cell carcinoma with unclear immunohistochemical
      features (8.6%), and 11 cases were large cell carcinoma with null
      immunohistochemical features (11.8%). No significant differences in clinical
      features were found among various immunophenotypes. The overall survival of 1, 3
      and 5 years of all cases was 51.0%, 5.4% and 1.1%, respectively and the mean
      survival was (15.2+/-1.2)months. Notably the null type had the lowest survival
      rate of 18% in one year, significantly worse than those of solid adenocarcinoma
      and non-keratinzing squamous cell carcinoma. CONCLUSIONS: The 2015 WHO
      classification based on immunohistochemical phenotype replaces the morphological
      approach in separating poorly differentiated non-small cell lung carcinoma from
      the former large cell lung carcinoma. The null immunohistochemical subtype may
      represent a distinct subtype of undifferentiated carcinoma with the worst
      prognosis.

PMID- 27033386
TI  - [Cytology of basaloid squamous cell carcinoma and small cell carcinoma of lung: a
      comparative study].
AB  - OBJECTIVE: To evaluate the roles of cytomorphology and immunohistochemistry in
      distinguishing between basaloid squamous cell carcinoma (BSC) and small cell
      carcinoma (SCC) of lung. METHODS: The direct smears and/or liquid-based cytology
      preparation (ThinPrep) of bronchial brushing/washing and fine-needle aspiration
      (FNA) specimens from 17 cases of biopsy-proven BSC of lung were retrospectively
      reviewed and compared with those from 17 cases of SCC. The cytomorphologic
      parameters analyzed included proportion of cohesive cell clusters, cell
      palisades/rosettes, adenoid cystic features, crushing artifact, nuclear maximum
      diameter, nuclear molding, scantiness of cytoplasm,"salt-and-pepper"nuclei,
      distinct nucleoli, spindly configuration, individual cell keratinization,
      necrosis, hyaline material, apoptosis and mitotic activity.
      Immunocytochemical/immunohistochemical study of 25 cases was performed. Ten FNA
      samples of basaloid squamous cell carcinoma were also analyzed for epidermal
      growth factor receptor mutations in exons 18, 19, 20 and 21 using amplification
      refractory mutation system. RESULTS: Most of the 17 BSC cases (15/17) showed a
      predominance of tightly cohesive tumor cell clusters. The proportion of isolated
      tumor cells was high in SCC (more than 60% in 14 cases). The nuclear maximum
      diameter of BSC was slightly larger than that of SCC (9 to 11 MUm in BSC versus 7
      to 9 MUm in SCC)."Salt-in-pepper"nuclei, nuclear molding and crushing artifact
      were detected in all SCC cases (15/17, 17/17 and 14/17, respectively). These
      features were only occasionally found in BSC group. Nucleoli were present in BSC
      and rarely (2/17) in SCC. Only 9 of 17 BSC cases showed individual cell
      keratinization. The differences in the above-mentioned cytomorphologic features
      were statistically significance (P<0.05). The results of immunohistochemistry
      performed on the cell block sections and immunocytochemistry performed on the
      ThinPrep slides were identical to that performed on the corresponding biopsy
      specimens. The tumor cells in BSC were consistently positive for CK5, p40 and
      p63. TTF1, chromogranin A, synaptophysin and CD56 were positive in most of SCC.
      One of SCC cases showed focal PAX5 expression. No EGFR mutations were detected in
      the 10 BSC cases studied. CONCLUSIONS: Selected cytomorphologic features,
      including presence of cohesive cell clusters, larger nuclear size, distinct
      nucleoli, lack of crushing artifact, absence of nuclear molding and presence of
      individual cell keratinization, are helpful in diagnosing BSC on cytology
      specimens. Immunohistochemistry using a panel of TTF1, CK5, p40/p63 and
      chromogranin A/synaptophysin/CD56 provides further clues in differential
      diagnosis between BSC and SCC. EGFR mutation study is often negative in lung BSC.

PMID- 27033387
TI  - [Intraductal papillary neoplasms of intrahepatic bile duct: a clinicopathologic
      study of 25 cases].
AB  - OBJECTIVE: To study the clinicopathologic and immunohistochemical features of
      intraductal papillary neoplasms of the bile duct (IPNB) of the intrahepatic bile
      duct. METHODS: The clinical findings, morphologic features and immunophenotype of
      25 cases of IPNB were investigated. RESULTS: Of the 25 cases of IPNB, 18 were in
      the left lobe, 6 were in the hilar bile duct, and 1 was in the right lobe. The
      average age was 60.6 (26-73) years. The presenting symptom was abdominal pain in
      15 cases. Imaging results were variable, including multilobular cysts, mass
      lesions within the dilated ducts, cholangiolithiasis with dilated bile duct, and
      solid mass. Gross examinations were concordant with imaging findings.
      Microscopically, all the IPNB could be divided into four papillary patterns,
      including 12 gastric type, 8 intestinal type, 4 pancreatobiliary type and 1
      oncocytic type. Five IPNB showed mild to moderate atypia, 10 showed high-grade
      atypia and 10 IPNB were associated with carcinomas.The invasive IPNB were mainly
      bile duct adenocarcinomas(9 cases), and rarely colloid carcinoma (1 case).
      Immunohistochemically, IPNB expressed MUC5AC (96.0%, 24/25), MUC2 (32.0%, 8/25),
      MUC6 (40.0%, 10/25) and MUC1 (12.0%, 3/25). The different MUC expression was
      commonly associated with specific histological subtype. CONCLUSIONS: IPNBs are
      rare cystic and premalignant neoplasms of the liver. The imaging features vary,
      but show a common feature of dilated bile duct. The pathologic types and
      classifications are similar to intraductal papillary mucinous neoplasm of the
      pancreas. The MUC stains are helpful in diagnosis and histological subtyping.

PMID- 27033388
TI  - [Clinicopathologic features of solitary fibrous tumor in urogenital system].
AB  - OBJECTIVE: To study the clinicopathologic features and differential diagnosis of
      solitary fibrous tumor (SFT) in the urogenital system. METHODS: The clinical data
      and pathologic characteristics of eight cases of SFT in the urogenital system
      were analyzed, and the relevant literature was reviewed. RESULTS: The cohort
      included six male and two female patients, with age of onset ranging from 25 to
      80 years. Five occurred in the kidney (three in the right kidney), one case each
      occurred in the bladder, the prostate and the spermatic cord. Most patients
      showed no obvious clinical symptoms or only had low back pain and swelling. The
      diameter of the tumor was ranged from 2.5 to 11.8 cm (median 5.2 cm). Microscopy
      showed at low magnification, the tumor cells were spindle-shaped and arranged in
      bundles or helicoid pattern. The regional mesenchymal fibroblasts showed
      hyperplasia, with obvious collagenization and formed hemangiopericytoma-like
      structure. One case showed increased mitotic figures (>5 cells/10 HPF) and focal
      necrosis. By immunohistochemistry, the tumor cells were positive for CD34 and
      STAT6 in all eight cases, CD99 and vimentin in six cases, bcl-2 in four cases and
      SMA in one case. All seven cases with follow-up did not show any tumor recurrence
      or metastasis. CONCLUSIONS: SFT is rare in the urogenital system and most
      patients show good prognosis. SFT expresses CD34 and STAT6 and needs to be
      distinguished from other spindle cell tumors.

PMID- 27033389
TI  - [Clinicopathologic study of pediatric vascular anomalies: a report of 117 cases].
AB  - OBJECTIVE: To study the clinicopathologic features of pediatric vascular
      anomalies and application of ISSVA classification. METHODS: The clinical
      features, histopathologic findings and immunohistochemical results were analyzed
      in 117 cases of pediatric vascular anomalies encountered during the period from
      May 2014 to May 2015. RESULTS: A total of 117 cases of vascular anomalies were
      studied. The age of patients ranged from 18 hours after birth to 11 years (mean
      age =34 months and median age =27 months). There were 73 male patients and 44
      female patients, with the male-to-female ratio being 1.7?1.0. Congenital skin
      lesions were found in 37 cases (31.6%). The common sites of involvement included
      head and neck region (46 cases, 39.3%), trunk (28 cases, 23.9%), extremities (14
      cases, 12.0%) and internal viscera (31 cases, 26.5%). According to the new ISSVA
      classification, there were 74 cases of vascular malformations and 43 cases of
      vascular neoplasms (ratio=1.7?1.0). The commonest vascular tumor encountered was
      infantile hemangioma (21 cases, 48.8%), including 17 cases in proliferative phase
      and 4 cases in involutive phase. Thirteen cases (23.3%) of congenital hemangioma
      were found, with 8 cases of rapidly involuting congenital hemangioma and 5 cases
      of non-involutive congenital hemangioma. Three of the congenital hemangioma
      occurred in liver. There were 5 cases (11.6%) of pyogenic granuloma, 3 cases
      (7.0%) of tufted angioma and 1 case (2.3%) of Kaposiform hemangioendothelioma.
      Amongst the 74 cases of vascular malformations encountered, lymphatic
      malformation was found in 47 cases (63.5%), venous malformation in 15 cases
      (20.2%), lymphatic-venous malformation in 11 cases (14.9%) and arteriovenous
      malformation in 1 case (1.4%). All cases of vascular anomalies were all positive
      for CD31 on immunostaining. Glut1 and CD15 were positive both in proliferative
      and involutive phases of the 21 cases of infantile hemangioma, while other
      vascular tumors and vascular malformations were negative. Forty-seven cases of
      lymphatic malformation and 11 cases of lymphatic-venous malformation showed D2-40
      expression. Focal positivity for D2-40 was demonstrated in 3 cases of tufted
      angioma and 1 case of Kaposiform hemangioendothelioma. CONCLUSIONS: Vascular
      anomalies affecting infants and children include tumors and malformations.
      Accurate histopathologic diagnosis and ISSVA classification of the various types
      of vascular anomalies play an important role in clinical management.

PMID- 27033390
TI  - [Clinicopathologic analysis of tubulocystic renal cell carcinoma with poorly
      differentiated foci].

PMID- 27033391
TI  - [Inflammatory myofibroblastic tumor in breast:a clinicopathologic study of 2
      cases].

PMID- 27033392
TI  - [Comparative analysis of different hematoxylin and eosin staining systems].

PMID- 27033393
TI  - [Application of PDCA circulation in sustainable quality improvement of paraffin
      embedded sections].

PMID- 27033394
TI  - [Different epidermal growth factor receptor gene mutations in a patient with
      multiple synchronous adenocarcinomas of lung:report of a case].

PMID- 27033395
TI  - [Metaplastic thymoma:report of 2 cases].

PMID- 27033396
TI  - [Tubulovillous adenoma of prostatic urethra:report of a case].

PMID- 27033397
TI  - [Spindle cell carcinoid tumor of kidney:report of a case].

PMID- 27033398
TI  - [Hepatocellular carcinoma with squamous features:report of a case].

PMID- 27033399
TI  - [Dendritic fibromyxolipoma of jaw: report of a case].

PMID- 27033400
TI  - [Pathologic diagnosis and differential diagnosis of urothelial carcinoma with
      chordoid features or abundant myxoid stroma].

PMID- 27033401
TI  - [Significance and evaluation of tumor-infiltrating lymphocytes in breast cancer].

PMID- 27033402
TI  - [Research progress on RNA-induced transcriptional gene regulation].

PMID- 27033403
TI  - Adsorption sites of single noble metal atoms on the rutile TiO2 (1 1 0) surface
      influenced by different surface oxygen vacancies.
AB  - Atomic adsorption of Au and Pt on the rutile (1 1 0) surface was investigated by
      atomic-resolution aberration-corrected scanning transmission electron microscopy
      (STEM) measurements combined with density functional theory calculations. Au
      single atoms were deposited on the surface in a vacuum condition, and the
      observed results were compared with Pt single atoms on the same surface prepared
      by the same experimental manner. It was found that Au single atoms are stably
      adsorbed only at the bridging oxygen vacancy sites, which is quite different from
      Pt single atoms exhibiting the most frequently observed adsorption at the basal
      oxygen vacancy sites. Such a difference in oxygen-vacancy effect between Au and
      Pt can be explained by electronic structures of the surface vacancies as well as
      characters of outermost atomic orbitals of Au and Pt.

PMID- 27033404
TI  - Peimine, a main active ingredient of Fritillaria, exhibits anti-inflammatory and
      pain suppression properties at the cellular level.
AB  - Fritillaria is one of the most important herbs in Chinese traditional medicine
      and represents an annual ?700 million industry. It is often used as an anti
      inflammatory, pain relieving and antitussive medicine. However, the mechanisms of
      these effects are still unclear. Peimine is one of active ingredients of
      Fritillaria. Using the patch-clamp technique, we profiled the action of Peimine
      against selected ion channels stably expressed in HEK 293 cell lines. Our data
      indicated that Peimine was not only able to block the Nav1.7 ion channel but also
      preferably inhibited the Kv1.3 ion channel. Thus, the study suggested potential
      mechanisms of Fritillaria as a pain relieving and anti-inflammatory herb. 

PMID- 27033405
TI  - Practical carbon-carbon bond formation from olefins through nickel-catalyzed
      reductive olefin hydrocarbonation.
AB  - New carbon-carbon bond formation reactions expand our horizon of retrosynthetic
      analysis for the synthesis of complex organic molecules. Although many methods
      are now available for the formation of C(sp(2))-C(sp(3)) and C(sp(3))-C(sp(3))
      bonds via transition metal-catalyzed cross-coupling of alkyl organometallic
      reagents, direct use of readily available olefins in a formal fashion of
      hydrocarbonation to make C(sp(2))-C(sp(3)) and C(sp(3))-C(sp(3)) bonds remains to
      be developed. Here we report the discovery of a general process for the
      intermolecular reductive coupling of unactivated olefins with alkyl or aryl
      electrophiles under the promotion of a simple nickel catalyst system. This new
      reaction presents a conceptually unique and practical strategy for the
      construction of C(sp(2))-C(sp(3)) and C(sp(3))-C(sp(3)) bonds without using any
      organometallic reagent. The reductive olefin hydrocarbonation also exhibits
      excellent compatibility with varieties of synthetically important functional
      groups and therefore, provides a straightforward approach for modification of
      complex organic molecules containing olefin groups. 

PMID- 27033406
TI  - Dual mode adaptive fractional order PI controller with feedforward controller
      based on variable parameter model for quadruple tank process.
AB  - The Quadruple Tank Process (QTP) is a well-known benchmark of a nonlinear coupled
      complex MIMO process having both minimum and nonminimum phase characteristics.
      This paper presents a novel self tuning type Dual Mode Adaptive Fractional Order
      PI controller along with an Adaptive Feedforward controller for the QTP. The
      controllers are designed based on a novel Variable Parameter Transfer Function
      model. The effectiveness of the proposed model and controllers is tested through
      numerical simulation and experimentation. Results reveal that the proposed
      controllers work successfully to track the reference signals in all ranges of
      output. A brief comparison with some of the earlier reported similar works is
      presented to show that the proposed control scheme has some advantages and better
      performances than several other similar works. 

PMID- 27033408
TI  - Midterm Follow-Up of the Stentless Freedom Solo Bioprosthesis in 350 Patients.
AB  - BACKGROUND: The stentless Freedom Solo aortic bioprosthesis is implanted
      supraannularly using one running suture line in the sinuses of Valsalva. We
      report our 9-year experience with this bioprosthesis. METHODS: From April 2005 to
      July 2014, 350 consecutive patients at our institution underwent aortic valve
      replacement with the Freedom Solo bioprosthesis. Follow-up and echocardiographic
      data were collected retrospectively from referring cardiology centers. RESULTS:
      The mean age was 76 +/- 6 years, 48% were male, and 46% underwent a concomitant
      procedure. Median EuroSCORE II was 3.0 (interquartile range, 1.9 to 4.9).
      Operative mortality was 5.1% for all procedures and 2.1% for isolated aortic
      valve replacement. The 1-, 5-, and 9-year overall survival was 92%, 74%, and 47%,
      respectively. At 6 years, freedom from structural valve deterioration and freedom
      from aortic valve reoperation were 98% and 96%, respectively. Prosthetic valve
      endocarditis occurred at a rate of 0.8% per patient-year. Permanent pacemaker
      implantation was necessary in 2.3% (n = 8), and moderate and severe prosthesis
      patient mismatch occurred in 30 patients overall (9.6%). Postoperative maximum
      and mean valvular gradients were 17 mm Hg and 10 mm Hg, respectively, and
      remained stable during follow-up. CONCLUSIONS: Aortic valve replacement with the
      Freedom Solo is safe and has a low rate of permanent pacemaker implantations and
      prosthesis-patient mismatch. Survival is comparable to that with other aortic
      bioprostheses, and structural valve deterioration and aortic valve reoperation
      are infrequent during midterm follow-up. Hemodynamic performance is excellent,
      with low valvular gradients that remain stable during follow-up.

PMID- 27033407
TI  - Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein
      epsilon4 on memory decline in older adults.
AB  - Apolipoprotein epsilon4 (ApoE4) is a strong genetic risk factor for sporadic
      Alzheimer's disease and memory decline in older adults. A single-nucleotide
      polymorphism in the cholesteryl ester transfer protein (CETP) gene (isoleucine to
      valine; V405) is associated with slower memory decline and a lower risk of
      Alzheimer's disease. As both genes regulate cholesterol, we hypothesized that the
      favorable CETPV405 allele may buffer the effect of ApoE4 on memory decline in
      older adults. Using linear regression, we examined the interactive effect of
      ApoE4 by CETPV405 on memory decline among 909 community-dwelling, nondemented,
      older adults (>=70 years) from the Einstein Aging Study. Episodic memory was
      measured using the picture version of the Free and Cued Selective Reminding Test
      with immediate recall (pFCSRT+IR). There was a significant ApoE * CETP
      interaction on decline in pFCSRT+IR scores (p = 0.01). ApoE4 carriers experienced
      faster decline than noncarriers among CETPI405I homozygotes (p = 0.007) and in
      CETPI405V heterozygotes (p = 0.015) but not in CETPV405V homozygotes (p = 0.614).
      Results suggest that the CETPV405 allele buffers ApoE4-associated memory decline
      in a gene dose-dependent manner. 

PMID- 27033409
TI  - What is the utility of using syndromic surveillance systems during large
      subnational infectious gastrointestinal disease outbreaks? An observational study
      using case studies from the past 5 years in England.
AB  - Syndromic surveillance systems in England have demonstrated utility in the early
      identification of seasonal gastrointestinal illness (GI) tracking its spatio
      temporal distribution and enabling early public health action. There would be
      additional public health utility if syndromic surveillance systems could detect
      or track subnational infectious disease outbreaks. To investigate using syndromic
      surveillance for this purpose we retrospectively identified eight large GI
      outbreaks between 2009 and 2014 (four randomly and four purposively sampled). We
      then examined syndromic surveillance information prospectively collected by the
      Real-time Syndromic Surveillance team within Public Health England for evidence
      of possible outbreak-related changes. None of the outbreaks were identified
      contemporaneously and no alerts were made to relevant public health teams.
      Retrospectively, two of the outbreaks - which happened at similar times and in
      proximal geographical locations - demonstrated changes in the local trends of
      relevant syndromic indicators and exhibited a clustering of statistical alarms,
      but did not warrant alerting local health protection teams. Our suite of
      syndromic surveillance systems may be more suited to their original purposes than
      as means of detecting or monitoring localized, subnational GI outbreaks. This
      should, however, be considered in the context of this study's limitations;
      further prospective work is needed to fully explore the use of syndromic
      surveillance for this purpose. Provided geographical coverage is sufficient,
      syndromic surveillance systems could be able to provide reassurance of no or
      minor excess healthcare systems usage during localized GI incidents.

PMID- 27033410
TI  - Pallidal stimulation for medically intractable blepharospasm.
AB  - Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an
      established procedure to improve generalised, segmental craniofacial dystonia.
      However, no studies have addressed the applicability of DBS for blepharospasm as
      a focal craniofacial dystonia. A 52-year-old man developed medically intractable
      involuntary eye closure. Because the abnormal movement was observed exclusively
      in the eyelids, he was diagnosed not with Meige's syndrome but with blepharospasm
      as a focal craniofacial dystonia. He underwent stereotactic surgery under general
      anaesthesia for bilateral GPi-DBS. Continuous GPi stimulation almost completely
      abolished the blepharospasm. 15 months after the operation, his preoperative
      scores on the Burke-Fahn-Marsden Dystonia Rating Scale (=8 points) decreased to 1
      (87.5% improvement). The present study demonstrates the applicability of GPi-DBS
      for treating blepharospasm presenting as focal dystonia. Further studies with
      accumulated case series are needed to confirm the effect of DBS on blepharospasm
      and other focal craniofacial dystonias.

PMID- 27033411
TI  - Hypoxia inhibits pulmonary artery endothelial cell apoptosis via the e
      selectin/biliverdin reductase pathway.
AB  - Hypoxia-induced inhibition of apoptosis in pulmonary artery endothelial cells
      (PAECs) has an important role in pulmonary arterial remodeling leading to
      aggravated hypoxic pulmonary arterial hypertension. However, the mechanisms
      involved in the hypoxia-induced inhibition of PAEC apoptosis have not been
      elucidated. e-selectin and biliverdin reductase (BVR) have been reported to
      contribute to the cascade of apoptosis in several cell lines but not in PAECs. In
      the present study, we show that the expression of e-selectin and BVR was both up
      regulated by hypoxia in PAECs. Moreover, hypoxia attenuated the decreased cell
      survival and apoptotic protein expression, and increased DNA fragmentation
      induced by serum deprivation in the PAECs, which was mediated by the e
      selectin/BVR pathway. In addition, by examining the mitochondrial membrane
      potential and mitochondrial membrane proteins (Bcl-2 and BAX), we show that the
      mitochondrial-dependent apoptosis pathway was necessary for the e-selectin/BVR
      pathway inducing the anti-apoptotic effect of hypoxia in PAECs. Taken all
      together, our data show that the e-selectin/BVR pathway participates in the
      inhibitory process of hypoxia in PAEC apoptosis which is mediated by the
      mitochondrial-dependent apoptosis pathway.

PMID- 27033412
TI  - Precise quantification of cellular uptake of cell-penetrating peptides using
      fluorescence-activated cell sorting and fluorescence correlation spectroscopy.
AB  - Cell-penetrating peptides (CPPs) have emerged as a potentially powerful tool for
      drug delivery due to their ability to efficiently transport a whole host of
      biologically active cargoes into cells. Although concerted efforts have shed some
      light on the cellular internalization pathways of CPPs, quantification of CPP
      uptake has proved problematic. Here we describe an experimental approach that
      combines two powerful biophysical techniques, fluorescence-activated cell sorting
      (FACS) and fluorescence correlation spectroscopy (FCS), to directly, accurately
      and precisely measure the cellular uptake of fluorescently-labeled molecules.
      This rapid and technically simple approach is highly versatile and can readily be
      applied to characterize all major CPP properties that normally require multiple
      assays, including amount taken up by cells (in moles/cell), uptake efficiency,
      internalization pathways, intracellular distribution, intracellular degradation
      and toxicity threshold. The FACS-FCS approach provides a means for quantifying
      any intracellular biochemical entity, whether expressed in the cell or introduced
      exogenously and transported across the plasma membrane. 

PMID- 27033413
TI  - Estradiol-17beta increases 12- and 15-lipoxygenase (type2) expression and
      activity and reactive oxygen species in human umbilical vascular smooth muscle
      cells.
AB  - The net vascular effect of estrogens on the vasculature is still under debate.
      Here we tested the effects of estradiol- 17beta (E2) as well as estrogen-receptor
      subtype specific and non-specific agonists and antagonists on the expression and
      eicosanoid production of lipoxygenase (LO) enzymes expressed in culture human
      umbilical vascular smooth muscle cells (VSMC), the platelet type 12LO and 15LO
      type 2. E2 increased 12 and 15LO mRNA expression by 2-3 folds and elicited an
      acute 50% increase 12 and 15 hydroxyeicosatetraenoic acid (HETE) production.
      Neither estrogen receptor ERalpha nor ERbeta-specific agonists were able to
      reproduce the induction of LO expression, but E2-induced expression was
      effectively blocked by ER non-specific and receptor subtype specific antagonists.
      Because 12 and 15HETE can increase reactive oxygen species in other cell types,
      we tested the possibility that E2 could raise ROS through LO. Indeed, E2 as well
      as the LO products 12 and 15HETE increased reactive oxygen species (ROS) in VSMC.
      E2-dependent and HETE-induced ROS could be blocked by NAD (P) H-oxidase
      inhibitors and by the ER general antagonist ICI. E2-induced ROS was partially
      (~50%) blocked by the LO inhibitor baicalein, but the LO blocker had no effect on
      12 or 15HETE- induced ROS formation, thus suggesting that part of E2-dependent
      ROS generation resulted from E2-induced 12 and 15HETE. Collectively these
      findings unveil an unrecognized effect of E2 in human VSMC, to induce 12 and 15LO
      type 2 expression and activity and suggest that E2-dependent ROS formation in
      VSMC may be partially mediated by the induction of 12 and 15HETE.

PMID- 27033415
TI  - Incoming Editor-in-Chief.

PMID- 27033416
TI  - A response to Lindsey et al. "Wolbachia pipientis should not be split into
      multiple species: A response to Ramirez-Puebla et al.".

PMID- 27033414
TI  - Regulation of microglial survival and proliferation in health and diseases.
AB  - Microglia play an important role in the development and maintenance of the
      central nervous system (CNS) under homeostatic conditions as well as during
      neurodegenerative diseases. Recent observations in human genomics and advances in
      genetic mouse models have provided insights into signaling pathways that control
      development, survival, proliferation and function of microglia. Alteration of
      these pathways contributes to the pathogenesis of CNS diseases. Here we review
      the current literature regarding the roles of these microglial pathways in both
      the normal and diseased brain and discuss areas that require further
      investigation.

PMID- 27033417
TI  - Evaluating the efficacy of the new Ion PGM Hi-Q Sequencing Kit applied to
      bacterial genomes.
AB  - Benchtop NGS platforms are constantly evolving to follow new advances in
      genomics. Thus, the manufacturers are making improvements, such as the recent Ion
      PGM Hi-Q chemistry. We evaluate the efficacy of this new Hi-Q approach by
      comparing it with the former Ion PGM kit and the Illumina MiSEQ Nextera 3rd
      version. The Hi-Q chemistry showed improvement on mapping reads, with 49 errors
      for 10kbp mapped; in contrast, the former kit had 89 errors. Additionally, there
      was a reduction of 80% in erroneous variant detection with the Torrent Variant
      Caller. Also, an enhancement was observed in de novo assembly with a more
      confident result in whole-genome MLST, with up to 96% of the alleles assembled
      correctly for both tested microbial genomes. All of these advantages result in a
      final genome sequence closer to the performance with MiSEQ and will contribute to
      turn comparative genomic analysis a reliable task.

PMID- 27033418
TI  - Exchange Interactions on the Highest-Spin Reported Molecule: the Mixed-Valence
      Fe42 Complex.
AB  - The finding of high-spin molecules that could behave as conventional magnets has
      been one of the main challenges in Molecular Magnetism. Here, the exchange
      interactions, present in the highest-spin molecule published in the literature,
      Fe42, have been analysed using theoretical methods based on Density Functional
      Theory. The system with a total spin value S = 45 is formed by 42 iron centres
      containing 18 high-spin Fe(III) ferromagnetically coupled and 24 diamagnetic low
      spin Fe(II) ions. The bridging ligands between the two paramagnetic centres are
      two cyanide ligands coordinated to the diamagnetic Fe(II) cations. Calculations
      were performed using either small Fe4 or Fe3 models or the whole Fe42 complex,
      showing the presence of two different ferromagnetic couplings between the
      paramagnetic Fe(III) centres. Finally, Quantum Monte Carlo simulations for the
      whole system were carried out in order to compare the experimental and simulated
      magnetic susceptibility curves from the calculated exchange coupling constants
      with the experimental one. This comparison allows for the evaluation of the
      accuracy of different exchange-correlation functionals to reproduce such magnetic
      properties. 

PMID- 27033419
TI  - The influence of n-3 fatty acids on maternal behavior and brain monoamines in the
      perinatal period.
AB  - The aim of this study was to use n-3 fatty acid-deficient pregnant mice to assess
      maternal behavior in the perinatal period. Female mice were fed either an n-3
      fatty acid-deficient (n-3 Def) or -adequate (n-3 Adq) diet for two generations.
      The nest score and volume of the n-3 Def dams were lower than those of the n-3
      Adq dams. In the observation of the post-delivery conditions, 40% of the n-3 Def
      dams attacked their newborns or did not nurse them. The brain docosahexaenoic
      acid (DHA) levels of the n-3 Def dams were lower than those of the n-3 Adq dams.
      In the hippocampus, moreover, positive correlations were observed between the DHA
      and the 5-HT or 5-HIAA, and a negative correlation was observed between the DHA
      and the DA. These results suggest that dietary n-3 fatty acids may normalize the
      development of maternal behavior and prevent postpartum depression. 

PMID- 27033420
TI  - Importance of adequate sample sizes in fatty acid intervention trials.
AB  - Randomised controlled trials are the ideal way to assess the effects of
      interventions. Small trials are useful for generating pilot data to determine
      samples sizes for larger trials, but can produce unreliable or biased results if
      they are considered in their own right. We investigate the impact of small sample
      sizes due to either inadequate recruitment targets or high attrition rates on the
      results of fatty acid intervention trials. Data from our large trial of DHA
      supplementation during pregnancy with minimal attrition are used for
      illustration. Our findings demonstrate that recruiting fewer participants or
      neglecting to follow up difficult participants can lead to substantially
      different results and alter conclusions about the effectiveness of the
      intervention. Developing strategies for overcoming these inadequacies should be a
      top priority in fatty acid intervention trials. 

PMID- 27033421
TI  - Impact of simultaneous stimulation of 5-lipoxygenase and myeloperoxidase in human
      neutrophils.
AB  - Human neutrophil 5-lipoxygenase (5-LOX) oxidizes arachidonic acid (AA) to 5S
      hydro(pero)xy-6E,8Z,11Z, 14Z-eicosatetraenoic acid (5-H(p)ETE) and leukotriene
      (LT)A4, which is further converted to the chemoattractant LTB4. These cells
      contain also the heme enzyme myeloperoxidase (MPO) producing several potent
      oxidants such as hypochlorous acid (HOCl). Previously, it was shown that MPO
      metabolites influence 5-LOX product formation. Here, we addressed the question,
      whether a simultaneous activation of MPO and 5-LOX in neutrophils results in
      comparable changes of 5-LOX activity. Human neutrophils were stimulated with H2O2
      or phorbol 12-myristate 13-acetate (PMA) for MPO activation and subsequently
      treated with calcium ionophore A23187 inducing 5-LOX product formation on
      endogenous AA. Special attention was drawn to neutrophil vitality, formation of
      MPO-derived metabolites and redox status. The pre-stimulation with H2O2 resulted
      in a concentration-dependent increase in the ratio of 5-HETE to the sum of LTB4+6
      trans-LTB4 in consequence of MPO activation. Thereby no impairment of cell
      vitality and only a slightly reduction of total glutathione level was observed.
      An influence of MPO on 5-LOX product formation could be suggested using an MPO
      inhibitor. In contrast, the pre-stimulation with PMA resulted in different
      changes of 5-LOX product formation leading to a reduced amount of 5-HETE
      unaffected by MPO inhibition. Furthermore, impaired cell vitality and diminished
      redox status was detected after PMA stimulation. Nevertheless, a MPO-induced
      diminution of LTB4 was obvious. Further work is necessary to define the type of 5
      LOX modification and investigate the effect of physiological MPO activators. 

PMID- 27033422
TI  - Comment on Dornellas et al., Deleterious effects of lard-enriched diet on tissues
      fatty acids composition and hypothalamic insulin actions, Prostaglandins, Leukot.
      Essent. Fat. Acids., 102-103 (2015) 21-29.

PMID- 27033423
TI  - Specialised pro-resolving mediators of inflammation in inflammatory arthritis.
AB  - INTRODUCTION: Specialised pro-resolving mediators (SPM) are derived from n-3 long
      chain polyunsaturated fatty acids (n-3FA). They promote resolution of
      inflammation and may contribute to the beneficial effects of n-3FA in patients
      with arthritis. This study compared SPM in knee effusions and plasma of patients
      with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA.
      METHODS: Thirty six patients taking n-3FA undergoing arthrocentesis for an
      inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA
      (2.4g/day) for 4 weeks were studied. SPM in synovial fluid and plasma were
      measured by liquid chromatography-tandem mass spectrometry included 18
      hydroxyeicosapentaenoic acid (18-HEPE), the precursor of the E-series SPM (RvE1,
      RvE2, RvE3, 18R-RvE3), and 17-hydroxydocosahexaenoic acid (17-HDHA), the
      precursor of the D-series SPM (RvD1, 17R-RvD1, RvD2). Other SPM included
      protectin D1 (PD1), 10S,17S-dihydroxydocosahexaenoic acid (10,17S-DHDHA), maresin
      1 (MaR-1) and 14-hydroxydocosahexaenoic acid (14-HDHA) derived from
      docosahexaenoic acid (DHA). RESULTS: E- and D-series SPM and the precursors 18
      HEPE and 17-HDHA were present in synovial fluid and plasma of the patients with
      inflammatory arthritis. Plasma SPM were negatively related to erythrocyte
      sedimentation rate in arthritis patients (P<0.01) and synovial fluid RvE2 was
      negatively associated with pain score (P=0.02). Conversion from 18-HEPE and 17
      HDHA to E- and D-series SPM was greater in synovial fluid (P<0.01). Most plasma
      SPM in arthritis patients were elevated (P<0.05) compared with healthy
      volunteers, and conversion to E- and D-series SPM was greater (P<0.01).
      CONCLUSIONS: SPM are present in chronic knee effusions and although the levels
      are lower than in plasma, the association between synovial fluid RvE2 and reduced
      pain scores suggests that synthesis of SPM at the site of inflammation is a
      relevant mechanism by which n-3FA alleviate the symptoms of arthritis.

PMID- 27033424
TI  - Characteristics and Surgical Outcomes for Primary Malignant Melanoma of the
      Esophagus.
AB  - Primary malignant melanoma of the esophagus (PMME) is an extremely rare disease
      with poor prognosis. We summarized and analyzed the characteristics of 17 PMME
      patients (with average age of 57.5 +/- 10.3 years) who had received surgical
      resection in our center. The majority (13/17, 76.5%) of the patients were male.
      The percentage of patients with smoking and alcohol consumption was 41.2% and
      23.5%, respectively. The preoperative diagnosis rate was 35.3%. Lymph node
      metastasis mainly involved the mid-lower mediastinal and upper abdominal area.
      Primary tumors that invaded beyond the submucosa layer (T2-T4) had much higher
      tendency of lymph node metastasis than those restricted to the submucosa layer
      (T1) (6/8, 75.0% vs. 3/9, 33.3%, p = 0.086). The 1-year and 5-year survival rate
      of the patients was 51% and 10%, respectively, with median survival time being
      18.1 months. Survival analysis showed that TNM stage was a predictor for PMME
      prognosis (median survival time of 47.3 months vs. 8.0 months for stage I/II vs.
      stage III, respectively, p = 0.018), and multivariable Cox regression analysis
      revealed the independence of its prognostic value [HR (95% CI): 5.678 (1.125
      28.658), p = 0.035]. 

PMID- 27033425
TI  - Incident Ischemic Heart Disease After Long-Term Occupational Exposure to Fine
      Particulate Matter: Accounting for 2 Forms of Survivor Bias.
AB  - Little is known about the heart disease risks associated with occupational,
      rather than traffic-related, exposure to particulate matter with aerodynamic
      diameter of 2.5 um or less (PM2.5). We examined long-term exposure to PM2.5 in
      cohorts of aluminum smelters and fabrication workers in the United States who
      were followed for incident ischemic heart disease from 1998 to 2012, and we
      addressed 2 forms of survivor bias. Left truncation bias was addressed by
      restricting analyses to the subcohort hired after the start of follow up. Healthy
      worker survivor bias, which is characterized by time-varying confounding that is
      affected by prior exposure, was documented only in the smelters and required the
      use of marginal structural Cox models. When comparing always-exposed participants
      above the 10th percentile of annual exposure with those below, the hazard ratios
      were 1.67 (95% confidence interval (CI): 1.11, 2.52) and 3.95 (95% CI: 0.87,
      18.00) in the full and restricted subcohorts of smelter workers, respectively. In
      the fabrication stratum, hazard ratios based on conditional Cox models were 0.98
      (95% CI: 0.94, 1.02) and 1.17 (95% CI: 1.00, 1.37) per 1 mg/m(3)-year in the full
      and restricted subcohorts, respectively. Long-term exposure to occupational PM2.5
      was associated with a higher risk of ischemic heart disease among aluminum
      manufacturing workers, particularly in smelters, after adjustment for survivor
      bias.

PMID- 27033426
TI  - A systematic review in select countries of the role of the pharmacist in
      consultations and sales of non-prescription medicines in community pharmacy.
AB  - BACKGROUND: Much has been studied in regard to non-prescription medicines (NPMs),
      but the impact of greater emphasis toward patient self-selection of such agents
      is still not well understood, and evidence in the literature might be equivocal.
      OBJECTIVE: The aim was to examine whether or not pharmacist interventions are
      important in the sale of NPMs and to summarize the evidence of pharmacists'
      contribution in maintaining patient safety and improving the quality of
      consultations involving NPMs. METHODS: Seven online databases were searched to
      identify the literature on studies conducted within the UK and in countries
      comparable to the UK reporting on consultations and selling of NPMs published
      between 1980 and 2013. All study designs except for quantitative surveys were
      eligible for inclusion into the review. The data extraction and quality
      assessment were performed according to the National Institute for Health and Care
      Excellence guidelines. The data extracted from the studies were analyzed and
      presented qualitatively. RESULTS: Eighty-three studies from an original 12,879
      citations were included in this review. Just under half of the studies were
      published between 2000 and 2009 (n = 38; 46%). Thirty-three (44%) of the studies
      were conducted in the UK. The review showed that in terms of the contribution of
      community pharmacy staff in consultations for NPMs, non-pharmacist staff dealt
      with a large proportion of the consultations and pharmacists were usually
      involved in the consultation through referral from non-pharmacist staff member.
      Counseling was not consistently offered to everyone. Where counseling was
      provided it was not always of sufficient quality. Consultations were performed
      much better when symptoms were presented compared to when people made a direct
      product request. Pharmacists were reported to conduct better consultations than
      non-pharmacist staff. There was evidence to suggest that where counseling was
      appropriately provided this afforded the person a safe environment to utilize
      their NPMs. CONCLUSIONS: Seeking methods to develop better engagement with
      customers accessing pharmacy services for NPMs is necessary to enhance the
      interaction between these two parties. Efforts to enhance the community pharmacy
      environment to bring about a more positive experience for people using pharmacy
      is needed at present and will be important if the model for the selection of NPMs
      is modified in the UK. More studies are needed to allow a better understanding of
      the impact self-selection may have on patient safety in the community pharmacy
      context.

PMID- 27033427
TI  - Prevalence and predictors of non-evidence based proton pump inhibitor use among
      elderly nursing home residents in the US.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) can lead to several adverse effects
      among the elderly, particularly when used inappropriately or in contrast to
      evidence suggested protocols. OBJECTIVE: The aim of this study was to examine the
      prevalence and predictors of non-evidence based PPI use in elderly nursing home
      residents. METHODS: A cross-sectional study was conducted using data from the
      2004 National Nursing Home Survey (NNHS). The study sample included nursing home
      residents 65 years and older. Descriptive statistics were used to examine the
      prevalence of non-evidence based PPI use. Multivariable logistic regression was
      used to evaluate the patient and facility-level factors associated with non
      evidence based PPI use among the elderly nursing home residents. RESULTS: A total
      of 355,600 elderly nursing home residents received at least one PPI for an
      overall prevalence of 26.99%. Among those elderly receiving PPIs, 48.59% of the
      use was not evidence based. Multivariable logistic regression revealed that
      residents with osteoporosis (Odds Ratio (OR): 0.55, 95% CI: 0.45-0.68), SSRI
      users (OR: 0.81, 95% CI: 0.68-0.97) and those residing in micropolitan area (OR:
      0.79, 95% CI: 0.63-0.98) were negatively associated with prescription of PPIs
      without an indication. Patients with chronic cough (OR: 2.10, 95% CI: 1.12-3.96)
      and Medicare insurance (OR: 1.23, 95% CI: 1.01-1.50) were positively associated
      with prescription of PPIs without an indication. CONCLUSIONS: The current study
      found that almost half of the elderly nursing home residents used PPIs for non
      evidence based indications. Given the safety concerns and high non-evidence based
      use of PPIs in nursing homes, there is an urgent need to optimize PPI use in the
      elderly.

PMID- 27033429
TI  - Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients
      With Refractory Celiac Disease.
AB  - Refractory celiac disease is characterized by mucosal damage in patients with
      celiac disease despite a gluten-free diet. Little is known about the mechanisms
      that cause persistent intestinal inflammation in these patients. We performed a
      case-control study of 17 consecutive patients diagnosed with refractory celiac
      disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with
      uncomplicated celiac disease (controls) to determine whether refractory disease
      is associated with infection by lymphotropic oncogenic viruses. We performed real
      time PCR analyses of duodenal biopsy samples from all patients to detect Epstein
      Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, 
      II, or -III. We used in situ hybridization and immunohistochemical analyses to
      identify infected cells and viral proteins. We did not detect human herpesvirus-8
      or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12
      of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were
      positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P
      < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of
      latency- and replication-associated proteins confirmed active infection. Further
      studies are needed to determine whether EBV infection contributes to the
      pathogenesis of refractory celiac disease and enteropathy-associated T-cell
      lymphoma.

PMID- 27033430
TI  - Duodenal Glomus Tumor: A Rare Cause of Upper GI Bleeding.

PMID- 27033428
TI  - A Scoring System to Determine Risk of Delayed Bleeding After Endoscopic Mucosal
      Resection of Large Colorectal Lesions.
AB  - BACKGROUND & AIMS: After endoscopic mucosal resection (EMR) of colorectal
      lesions, delayed bleeding is the most common serious complication, but there are
      no guidelines for its prevention. We aimed to identify risk factors associated
      with delayed bleeding that required medical attention after discharge until day
      15 and develop a scoring system to identify patients at risk. METHODS: We
      performed a prospective study of 1214 consecutive patients with nonpedunculated
      colorectal lesions 20 mm or larger treated by EMR (n = 1255) at 23 hospitals in
      Spain, from February 2013 through February 2015. Patients were examined 15 days
      after the procedure, and medical data were collected. We used the data to create
      a delayed bleeding scoring system, and assigned a weight to each risk factor
      based on the beta parameter from multivariate logistic regression analysis.
      Patients were classified as being at low, average, or high risk for delayed
      bleeding. RESULTS: Delayed bleeding occurred in 46 cases (3.7%, 95% confidence
      interval, 2.7%-4.9%). In multivariate analysis, factors associated with delayed
      bleeding included age >=75 years (odds ratio [OR], 2.36; P < .01), American
      Society of Anesthesiologist classification scores of III or IV (OR, 1.90; P <=
      .05), aspirin use during EMR (OR, 3.16; P < .05), right-sided lesions (OR, 4.86;
      P < .01), lesion size >=40 mm (OR, 1.91; P <= .05), and a mucosal gap not closed
      by hemoclips (OR, 3.63; P <= .01). We developed a risk scoring system based on
      these 6 variables that assigned patients to the low-risk (score, 0-3), average
      risk (score, 4-7), or high-risk (score, 8-10) categories with a receiver
      operating characteristic curve of 0.77 (95% confidence interval, 0.70-0.83). In
      these groups, the probabilities of delayed bleeding were 0.6%, 5.5%, and 40%,
      respectively. CONCLUSIONS: The risk of delayed bleeding after EMR of large
      colorectal lesions is 3.7%. We developed a risk scoring system based on 6 factors
      that determined the risk for delayed bleeding (receiver operating characteristic
      curve, 0.77). The factors most strongly associated with delayed bleeding were
      right-sided lesions, aspirin use, and mucosal defects not closed by hemoclips.
      Patients considered to be high risk (score, 8-10) had a 40% probability of
      delayed bleeding.

PMID- 27033431
TI  - Xylarinase: a novel clot busting enzyme from an endophytic fungus Xylaria curta.
AB  - Xylarinase is a bi-functional fibrinolytic metalloprotease isolated from the
      culture filtrate of endophytic fungus Xylaria curta which is monomeric with a
      molecular mass of ~33.76 kDa. The enzyme displayed both plasmin and tissue
      plasminogen activator like activity under in vitro conditions. It hydrolyses
      Aalpha and Bbeta chains of the fibrinogen. Optimal fibrinolytic activity of
      xylarinase is observed at 35  degrees C, pH 8. Ca(2+) stimulated the fibrinolytic
      activity of xylarinase while Fe(2+) and Zn(2+) inhibited suggesting it to be a
      metalloprotease. The Km and Vmax values of xylarinase were 240.9 MUM and 1.10
      U/ml for fibrinogen and 246 MUM and 1.22 U/ml for fibrin, respectively.
      Xylarinase was found to prolong the activated partial thromboplastin time and
      prothrombin time. The N-terminal sequence of xylarinase (SNGPLPGGVVWAG) did not
      show any homology with previously known fibrinolytic enzymes. Thus xylarinase is
      a novel fibrinolytic metalloprotease which could be possibly used as a new clot
      busting enzyme. 

PMID- 27033432
TI  - [Training doctors for the future: A review 10 years later].

PMID- 27033433
TI  - [Health literacy: Implications for the health system].

PMID- 27033434
TI  - [Importance of multidisciplinary monitoring in Medicine: CHARGE syndrome].

PMID- 27033435
TI  - [Stress echocardiogram in the early diagnosis of systemic sclerosis-associated
      pulmonary hypertension].

PMID- 27033436
TI  - [Symptom alternatives in recurrent oral aphthosis].

PMID- 27033437
TI  - [JAK2 inhibitors].
AB  - Pharmacological inhibition of the kinase activity of JAK proteins can interfere
      with the signaling of immunomodulatory cytokines and block the constitutive
      activation of the JAK-STAT pathway that characterizes certain malignancies,
      including chronic myeloproliferative neoplasms. JAK inhibitors may, therefore, be
      useful to treat malignancies as well as inflammatory or immune disorders.
      Currently, the most significant advances have been made in the treatment of
      myelofibrosis, where these drugs may lead to a remarkable improvement in the
      control of hyperproliferative manifestations. However, available data suggest
      that this treatment is not curative of myelofibrosis. In general, JAK2 inhibition
      induces cytopaenias, with this being considered a class side-effect. By contrast,
      the extrahaematologic toxicity profile varies significantly among the different
      JAK inhibitors. At present, there are several clinical trials evaluating the
      combination of ruxolitinib with other drugs, in order to improve its therapeutic
      activity as well as reducing haematologic toxicity. 

PMID- 27033438
TI  - [Cutaneous and mucosal manifestations associated with cocaine use].
AB  - Complications due to cocaine are a public health problem. The typical cutaneous
      disease is leukocytoclastic vasculitis and/or thrombotic vasculopathy affecting
      mainly the ears. No intense systemic involvement is usually present, but there
      may be several cutaneous, mucosal and systemic manifestations. Other findings
      associated as arthralgia, neutropaenia or agranulocytosis, low titer positive
      antinuclear antibodies, antiphospholipid antibody positivity and neutrophil
      cytoplasmic antibodies against multiple antigens help the diagnosis. This disease
      requires a clinical suspicion with a clinical history, a complete physical
      examination and a broad differential diagnosis for an early and correct
      diagnosis. The course is usually self-limited. In most cases the only treatment
      is to discontinue the use of cocaine associated with symptomatic treatment, no
      proven benefit of systemic corticosteroids. 

PMID- 27033439
TI  - [Giant cell temporal arteritis and carotidynia].

PMID- 27033440
TI  - [Heart failure caused by ovarian carcinoid: Successful management with tumor
      resection].

PMID- 27033441
TI  - Thermodynamics of the Electron Acceptors in Heliobacterium modesticaldum: An
      Exemplar of an Early Homodimeric Type I Photosynthetic Reaction Center.
AB  - The homodimeric type I reaction center in heliobacteria is arguably the simplest
      known pigment-protein complex capable of conducting (bacterio)chlorophyll-based
      conversion of light into chemical energy. Despite its structural simplicity, the
      thermodynamics of the electron transfer cofactors on the acceptor side have not
      been fully investigated. In this work, we measured the midpoint potential of the
      terminal [4Fe-4S](2+/1+) cluster (FX) in reaction centers from Heliobacterium
      modesticaldum. The FX cluster was titrated chemically and monitored by (i) the
      decrease in the level of stable P800 photobleaching by optical spectroscopy, (ii)
      the loss of the light-induced g ~ 2 radical from P800(+*) following a single
      turnover flash, (iii) the increase in the low-field resonance at 140 mT
      attributed to the S = (3)/2 ground spin state of FX(-), and (iv) the loss of the
      spin-correlated P800(+) FX(-) radical pair following a single-turnover flash.
      These four techniques led to similar estimations of the midpoint potential for FX
      of -502 +/- 3 mV (n = 0.99), -496 +/- 2 mV (n = 0.99), -517 +/- 10 mV (n = 0.65),
      and -501 +/- 4 mV (n = 0.84), respectively, with a consensus value of -504 +/- 10
      mV (converging to n = 1). Under conditions in which FX is reduced, the long-lived
      (~15 ms) P800(+) FX(-) state is replaced by a rapidly recombining (~15 ns)
      P800(+)A0(-) state, as shown by ultrafast optical experiments. There was no
      evidence of the presence of a P800(+) A1(-) spin-correlated radical pair by
      electron paramagnetic resonance (EPR) under these conditions. The midpoint
      potentials of the two [4Fe-4S](2+/1+) clusters in the low-molecular mass
      ferredoxins were found to be -480 +/- 11 mV/-524 +/- 13 mV for PshBI, -453 +/- 6
      mV/-527 +/- 6 mV for PshBII, and -452 +/- 5 mV/-533 +/- 8 mV for HM1_2505 as
      determined by EPR spectroscopy. FX is therefore suitably poised to reduce one
      [4Fe-4S](2+/1+) cluster in these mobile electron carriers. Using the measured
      midpoint potential of FX and a quasi-equilibrium model of charge recombination,
      the midpoint potential of A0 was estimated to be -854 mV at room temperature. The
      midpoint potentials of A0 and FX are therefore 150-200 mV less reducing than
      their respective counterparts in Photosystem I of cyanobacteria and plants. This
      places the redox potential of the FX cluster in heliobacteria approximately
      equipotential to the highest-potential iron-sulfur cluster (FA) in Photosystem I,
      consistent with its assignment as the terminal electron acceptor.

PMID- 27033442
TI  - Ejaculation Frequency and Risk of Prostate Cancer: Updated Results with an
      Additional Decade of Follow-up.
AB  - BACKGROUND: Evidence suggests that ejaculation frequency may be inversely related
      to the risk of prostate cancer (PCa), a disease for which few modifiable risk
      factors have been identified. OBJECTIVE: To incorporate an additional 10 yr of
      follow-up into an original analysis and to comprehensively evaluate the
      association between ejaculation frequency and PCa, accounting for screening,
      clinically relevant disease subgroups, and the impact of mortality from other
      causes. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of
      participants in the Health Professionals Follow-up Study utilizing self-reported
      data on average monthly ejaculation frequency. The study includes 31925 men who
      answered questions on ejaculation frequency on a 1992 questionnaire and followed
      through to 2010. The average monthly ejaculation frequency was assessed at three
      time points: age 20-29 yr, age 40-49 yr, and the year before questionnaire
      distribution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence of total
      PCa and clinically relevant disease subgroups. Cox models were used to estimate
      hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS AND LIMITATIONS:
      During 480831 person-years, 3839 men were diagnosed with PCa. Ejaculation
      frequency at age 40-49 yr was positively associated with age-standardized body
      mass index, physical activity, divorce, history of sexually transmitted
      infections, and consumption of total calories and alcohol. Prostate-specific
      antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of
      prostate biopsy were similar across frequency categories. In multivariable
      analyses, the hazard ratio for PCa incidence for >=21 compared to 4-7
      ejaculations per month was 0.81 (95% confidence interval [CI] 0.72-0.92; p<0.0001
      for trend) for frequency at age 20-29 yr and 0.78 (95% CI 0.69-0.89; p<0.0001 for
      trend) for frequency at age 40-49 yr. Associations were driven by low-risk
      disease, were similar when restricted to a PSA-screened cohort, and were unlikely
      to be explained by competing causes of death. CONCLUSIONS: These findings provide
      additional evidence of a beneficial role of more frequent ejaculation throughout
      adult life in the etiology of PCa, particularly for low-risk disease. PATIENT
      SUMMARY: We evaluated whether ejaculation frequency throughout adulthood is
      related to prostate cancer risk in a large US-based study. We found that men
      reporting higher compared to lower ejaculatory frequency in adulthood were less
      likely to be subsequently diagnosed with prostate cancer.

PMID- 27033443
TI  - Ketamine decreases inflammatory and immune pathways after transient hypoxia in
      late gestation fetal cerebral cortex.
AB  - Transient hypoxia in pregnancy stimulates a physiological reflex response that
      redistributes blood flow and defends oxygen delivery to the fetal brain. We
      designed the present experiment to test the hypotheses that transient hypoxia
      produces damage of the cerebral cortex and that ketamine, an antagonist
      ofNMDAreceptors and a known anti-inflammatory agent, reduces the damage. Late
      gestation, chronically catheterized fetal sheep were subjected to a 30-min period
      of ventilatory hypoxia that decreased fetal PaO2from 17 +/- 1 to 10 +/- 1 mmHg,
      or normoxia (PaO217 +/- 1 mmHg), with or without pretreatment (10 min before
      hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after
      hypoxia/normoxia, fetal cerebral cortex was removed andmRNAextracted for
      transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia
      stimulated a transcriptomic response consistent with a reduction in cellular
      metabolism and an increase in inflammation. Ketamine pretreatment reduced both of
      these responses. The inflammation response modeled with transcriptomic systems
      biology was validated by immunohistochemistry and showed increased abundance of
      microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine
      significantly reduced. We conclude that transient hypoxia produces inflammation
      of the fetal cerebral cortex and that ketamine, in a standard clinical dose,
      reduces the inflammation response. 

PMID- 27033444
TI  - A key role of PGC-1alpha transcriptional coactivator in production of VEGF by a
      novel angiogenic agent COA-Cl in cultured human fibroblasts.
AB  - We previously demonstrated a potent angiogenic effect of a newly developed
      adenosine-like agent namedCOA-Cl.COA-Cl exerted tube forming activity in human
      umbilical vein endothelial cells in the presence of normal human dermal
      fibroblasts (NHDF). We therefore explored whether and howCOA-Cl modulates gene
      expression and protein secretion ofVEGF, a master regulator of angiogenesis,
      inNHDFRT-PCRandELISArevealed thatCOA-Cl upregulatedVEGF mRNAexpression and
      protein secretion inNHDFHIF1alpha(hypoxia-inducible factor 1alpha), a
      transcription factor, andPGC-1alpha(peroxisome proliferator-activated receptor
      gammacoactivator-1alpha), a transcriptional coactivator, are known to positively
      regulate theVEGFgene. Immunoblot andRT-PCRanalyses revealed thatCOA-Cl markedly
      upregulated the expression ofPGC-1alphaprotein andmRNACOA-Cl had no effect on the
      expression ofHIF1alphaprotein andmRNAin both hypoxia and normoxia. SilencingPGC
      1alphagene, but notHIF1alphagene, by small interferingRNAattenuated the ability
      ofCOA-Cl to promoteVEGFsecretion. When an N-terminal fragment ofPGC-1alphawas
      cotransfected with its partner transcription factorERRalpha(estrogen-related
      receptor-alpha) inCOS-7 cells,COA-Cl upregulated the expression of the
      endogenousVEGF mRNA However,COA-Cl had no effect on the expression ofVEGF,
      whenHIF1alphawas transfected.COA-Cl inducesVEGFgene expression and protein
      secretion in fibroblasts. The transcriptional coactivatorPGC-1alpha, in concert
      withERRalpha, plays a key role in theCOA-Cl-inducedVEGFproduction.COA-Cl-induced
      activation ofPGC-1alpha-ERRalpha-VEGFpathway has a potential as a novel means for
      therapeutic angiogenesis. 

PMID- 27033445
TI  - Similar degrees of obesity induced by diet or aging cause strikingly different
      immunologic and metabolic outcomes.
AB  - In obesity, adipose tissue (AT) and liver are infiltrated with Th-1 polarized
      immune cells, which are proposed to play an important role in the pathogenesis of
      the metabolic abnormalities of obesity. Aging is also associated with increased
      adiposity, but the effects of this increase on inflammation and associated
      metabolic dysfunction are poorly understood. To address this issue, we assessed
      insulin resistance (IR) andATand liver immunophenotype in aged, lean (AL) and
      aged, obese (AO) mice, all of whom were maintained on a standard chow diet (11%
      fat diet) throughout their lives. For comparison, these variables were also
      assessed in young, lean (YL) and young diet-induced obese mice (41% fat diet,YO).
      Despite similar body weight and fat accumulation,YOmice were substantially
      moreIRand had greater liver steatosis compared toAOmice.YOalso had elevated
      infiltration of macrophages/dendritic cells inATand liver, but these increases
      were absent inAO Furthermore, liver immune cells ofYOwere more Th-1 polarized
      thenAO Notably, aging was associated with accumulation of T cells, but this
      occurred independent of obesity. Together, the data suggest that reduced
      inflammation inAOunderlies the improved insulin sensitivity and lowered steatosis
      compared toYO. 

PMID- 27033446
TI  - Luminal flow induces NADPH oxidase 4 translocation to the nuclei of thick
      ascending limbs.
AB  - Superoxide (O2 (-)) exerts its physiological actions in part by causing changes
      in gene transcription. In thick ascending limbs flow-induced O2 (-)production is
      mediated byNADPHoxidase 4 (Nox4) and is dependent on protein kinase C (PKC).
      Polymerase delta interacting protein 2 (Poldip2) increases Nox4 activity, but it
      is not known whether Nox4 translocates to the nucleus and whether Poldip2
      participates in this process. We hypothesized that luminal flow causes Nox4
      translocation to the nuclei of thick ascending limbs in aPKC-dependent process
      facilitated by Poldip2. To test our hypothesis, we studied the subcellular
      localization of Nox4 and Poldip2 using confocal microscopy and O2 (-)production
      in the absence and presence of luminal flow. Luminal flow increased the ratio of
      nuclear to cytoplasmic intensity of Nox4 (N/C) from 0.3 +/- 0.1 to 0.7 +/- 0.1 (P
      < 0.01) and O2 (-)production from 89 +/- 15 to 231 +/- 16AU/s (P < 0.001). In the
      presence of flowPKCinhibition reduced N/C from 0.5 +/- 0.1 to 0.2 +/- 0.1 (P <
      0.01). Flow-induced O2 (-)production was also blocked (flow: 142 +/- 20AU/s; flow
      plusPKCinhibition 26 +/- 12AU/s;P < 0.01). The cytoskeleton disruptor
      cytochalasin D (1 MUmol/L) decreased flow-induced Nox4 translocation by 0.3 +/-
      0.01 (P < 0.01); however, it did not reduce flow-induced O2 (-) Flow did not
      alter Poldip2 localization. We conclude that: (1) luminal flow elicits Nox4
      translocation to the nucleus in aPKC- and cytoskeleton-dependent process; (2)
      Nox4 activation occurs before translocation; and (3) Poldip2 is not involved in
      Nox4 nuclear translocation. Flow-induced Nox4 translocation to the nucleus may
      play a role in O2 (-)-dependent changes in thick ascending limbs. 

PMID- 27033447
TI  - Indomethacin injury to the rat small intestine is dependent upon biliary
      secretion and is associated with overgrowth of enterococci.
AB  - NSAIDuse is limited due to the drugs' toxicity to the gastrointestinal mucosa, an
      action incompletely understood. Lower gut injury induced byNSAIDs is dependent on
      bile secretion and is reported to increase the growth of a number of bacterial
      species, including an enterococcal species,Enterococcus faecalis This study
      examined the relationships between indomethacin (INDO)-induced intestinal
      injury/bleeding, small bowel overgrowth (SBO) and dissemination of enterococci,
      and the contribution of bile secretion to these pathological responses. Rats
      received either a sham operation (SO) or bile duct ligation (BDL) prior to
      administration of two daily subcutaneous doses of saline orINDO, and 24 h later,
      biopsies of ileum and liver were collected for plating on selective bacterial
      media. Fecal hemoglobin (Hb) and blood hematocrit (Hct) were measured to assess
      intestinal bleeding. Of the four treatment groups, onlySO/INDOrats experienced a
      significant 10- to 30-fold increase in fecal Hb and reduction in Hct, indicating
      thatBDLattenuatedINDO-induced intestinal injury/bleeding. Ileal enterococcal
      colony-forming units were significantly increased (500- to 1000-fold)
      inSO/INDOrats. Of all groups, only theSO/INDOrats demonstrated gut injury, and
      this was associated with enterococcal overgrowth of the gut and dissemination to
      the liver. We also demonstrated thatINDO-induced intestinal injury andE.
      faecalisovergrowth was independent of the route of administration of the drug, as
      similar findings were observed in rats orally dosed with theNSAID Bile secretion
      plays an important role inINDO-induced gut injury and appears to support
      enterococcal overgrowth of the intestine.NSAID-induced enterococcalSBOmay be
      involved either as a compensatory response to gut injury or with the pathogenic
      process itself and the subsequent development of sepsis. 

PMID- 27033448
TI  - Increased presence of oxidized low-density lipoprotein in the left ventricular
      blood of subjects with cardiovascular disease.
AB  - OxidizedLDL(Ox-LDL) and oxidative stress have been implicated in both
      atherosclerosis and congestive heart failure (HF) development. Here, we tested
      whether Ox-LDLlevels in left ventricular blood (LVB) might differ from those of
      venous peripheral blood (PB), and whether the level might depend on cardiac
      function. We also tested whether theLDLmolecule is likely to have a longer
      residence time in the left ventricle ofHFsubjects with low ejection fraction
      (EF). The aim of this study was to determine Ox-LDLlevels, paraoxonase 1 (PON1)
      activity, and cholesterol efflux capacity (CEC) ofPBandLVB, and correlate these
      values withLVEF Sixty-oneHFpatients underwent preoperative transthoracic
      echocardiographic assessment of ventricular function.LVEFs were determined using
      Simpson's biplane technique.LVBandPBlevels of Ox-LDLwere determined, andPON1
      activity and plasma cholesterol efflux capacity were measured. A significant
      increase in the levels of Ox-LDLinLVBwas noted as compared to levels inPB, even
      whenEFwas near normal. However, as ejection fraction decreased, the level of Ox
      LDLinPBapproached that of theLVBPON1 activity and cholesterol efflux studies
      indicated increased oxidative stress inLVBand a decreased ability to promote
      cholesterol efflux from lipid-enriched macrophages. The results suggest thatLVBis
      more oxidatively stressed compared toPB, and thereforeLVtissue might be affected
      differently than peripheral tissues. We recently reported that brain natriuretic
      peptide (BNP), a marker forHF, is induced by Ox-LDL, so it is possible localized
      factors within theLVcould profoundly affect markers ofHF. 

PMID- 27033449
TI  - High glucose induces platelet-derived growth factor-C via carbohydrate response
      element-binding protein in glomerular mesangial cells.
AB  - Persistent high concentration of glucose causes cellular stress and damage in
      diabetes via derangement of gene expressions. We previously reported high glucose
      activates hypoxia-inducible factor-1alphaand downstream gene expression in
      mesangial cells, leading to an extracellular matrix expansion in the glomeruli. A
      glucose-responsive transcription factor carbohydrate response element-binding
      protein (ChREBP) is a key mediator for such perturbation of gene regulation. To
      provide insight into glucose-mediated gene regulation in mesangial cells, we
      performed chromatin immunoprecipitation followed byDNAmicroarray analysis and
      identified platelet-derived growth factor-C (PDGF-C) as a novel target gene of
      ChREBP In streptozotocin-induced diabetic mice, glomerular cells showed a
      significant increase inPDGF-C expression; the ratio ofPDGF-C-positive cells to
      the total number glomerular cells demonstrated more than threefold increase when
      compared with control animals. In cultured human mesangial cells, high glucose
      enhanced expression ofPDGF-C protein by 1.9-fold. Knock-down of ChREBPabrogated
      this induction response. UpregulatedPDGF-C contributed to the production of
      typeIVand typeVIcollagen, possibly via an autocrine mechanism. Interestingly,
      urinaryPDGF-C levels in diabetic model mice were significantly elevated in a
      fashion similar to urinary albumin. Taken together, we hypothesize that a high
      glucose-mediated induction ofPDGF-C via ChREBPin mesangial cells contributes to
      the development of glomerular mesangial expansion in diabetes, which may provide
      a platform for novel predictive and therapeutic strategies for diabetic
      nephropathy. 

PMID- 27033450
TI  - The contribution of Kv2.2-mediated currents decreases during the postnatal
      development of mouse dorsal root ganglion neurons.
AB  - Delayed rectifier voltage-gated K(+)(Kv) channels play an important role in the
      regulation of the electrophysiological properties of neurons. In mouse dorsal
      root ganglion (DRG) neurons, a large fraction of the delayed rectifier current is
      carried by both homotetrameric Kv2 channels and heterotetrameric channels
      consisting of Kv2 and silent Kv (KvS) subunits (i.e., Kv5-Kv6 and Kv8-Kv9).
      However, little is known about the contribution of Kv2-mediated currents during
      the postnatal development ofDRGneurons. Here, we report that the Stromatoxin-1
      (ScTx)-sensitive fraction of the total outward K(+)current (IK) from
      mouseDRGneurons gradually decreased (~13%,P < 0.05) during the first month of
      postnatal development. Because ScTx inhibits both Kv2.1- and Kv2.2-mediated
      currents, this gradual decrease may reflect a decrease in currents containing
      either subunit. However, the fraction of Kv2.1 antibody-sensitive current that
      only reflects the Kv2.1-mediated currents remained constant during that same
      period. These results suggested that the fractional contribution of Kv2.2
      mediated currents relative toIKdecreased with postnatal age. SemiquantitativeRT
      PCRanalysis indicated that this decrease can be attributed to developmental
      changes in Kv2.2 expression as themRNAlevels of the Kv2.2 subunit decreased
      gradually between 1 and 4 weeks of age. In addition, we observed age-dependent
      fluctuations in themRNAlevels of the Kv6.3, Kv8.1, Kv9.1, and Kv9.3 subunits.
      These results support an important role of both Kv2 and KvS subunits in the
      postnatal maturation ofDRGneurons. 

PMID- 27033451
TI  - Heterozygous caveolin-3 mice show increased susceptibility to palmitate-induced
      insulin resistance.
AB  - Insulin resistance and diabetes are comorbidities of obesity and affect one in 10
      adults in the United States. Despite the high prevalence, the mechanisms of
      cardiac insulin resistance in obesity are still unclear. We test the hypothesis
      that the insulin receptor localizes to caveolae and is regulated through binding
      to caveolin-3 (CAV3). We further test whether haploinsufficiency forCAV3
      increases the susceptibility to high-fat-induced insulin resistance. We used in
      vivo and in vitro studies to determine the effect of palmitate exposure on global
      insulin resistance, contractile performance of the heart in vivo, glucose uptake
      in the heart, and on cellular signaling downstream of theIR We show that
      haploinsufficiency forCAV3 increases susceptibility to palmitate-induced global
      insulin resistance and causes cardiomyopathy. On the basis of fluorescence energy
      transfer (FRET) experiments, we show thatCAV3 andIRdirectly interact in
      cardiomyocytes. Palmitate impairs insulin signaling by a decrease in insulin
      stimulated phosphorylation of Akt that corresponds to an 87% decrease in insulin
      stimulated glucose uptake inHL-1 cardiomyocytes. Despite loss of Akt
      phosphorylation and lower glucose uptake, palmitate increased insulin-independent
      serine phosphorylation ofIRS-1 by 35%. In addition, we found lipid induced
      downregulation ofCD36, the fatty acid transporter associated with caveolae. This
      may explain the problem the diabetic heart is facing with the simultaneous
      impairment of glucose uptake and lipid transport. Thus, these findings suggest
      that loss ofCAV3 interferes with downstream insulin signaling and lipid uptake,
      implicatingCAV3 as a regulator of theIRand regulator of lipid uptake in the
      heart. 

PMID- 27033452
TI  - Exploring the mechanisms underpinning sweating: the development of a specialized
      ventilated capsule for use with intradermal microdialysis.
AB  - Many studies have aimed to identify the controllers of sweating using ventilated
      capsules with intradermal microdialysis. It is unclear, however, if the surface
      area covered by the capsule influences the observed response as a result of
      differences in the number of sweat glands affected by the infused pharmacological
      agent relative to the total glands captured by the capsule. We evaluated the area
      of skin perfused with agents delivered via microdialysis. Thereafter, we
      developed a specialized sweat capsule (1.1 cm(2)) and compared the sweating
      response with a classic capsule (2.8 cm(2)). InProtocol 1(n = 6), methacholine
      was delivered to forearm skin in a dose-dependent manner (1-2000 mmol L(-1)). The
      area of activated sweat glands was assessed via the modified iodine-paper
      technique. InProtocol 2(n = 6), the area of inhibited sweat glands induced by
      ouabain and atropine was assessed during moderate-intensity cycling. Marked
      variability in the affected skin area was observed (0.9 +/- 0.4 to 5.2 +/- 1.1
      cm(2)). InProtocol 3(n = 6), we compared the attenuation in local sweat rate
      (LSR) induced by atropine between the new and classic capsule during moderate
      intensity cycling. Atropine attenuated sweating as assessed using the new
      (control: 0.87 +/- 0.23 mg min(-1) cm(-2)vs. atropine: 0.54 +/- 0.22 mg min(-1)
      cm(-2);P < 0.01) and classic (control: 0.85 +/- 0.33 mg min(-1) cm(-2)vs.
      atropine: 0.60 +/- 0.26 mg min(-1) cm(-2);P = 0.05) capsule designs. Importantly,
      responses did not differ between capsule designs (P = 0.23). These findings
      provide critical information regarding the skin surface area perfused by
      microdialysis and suggest that use of a larger capsule does not alter the
      mechanistic insight into the sweating response gained when using microdialysis. 

PMID- 27033453
TI  - Lithium decreases the effects of neuronal calcium sensor protein 1 in
      pedunculopontine neurons.
AB  - Human postmortem studies reported increased expression of neuronal calcium sensor
      protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or
      aberrant gamma band activity is present in the same disorder. Bipolar disorder is
      characterized by sleep dysregulation, suggesting a role for the reticular
      activating system (RAS). Lithium (Li(+)) has been shown to effectively treat the
      mood disturbances in bipolar disorder patients and was proposed to act by
      inhibiting the interaction betweenNCS-1 and inositol 1,4,5-triphosphate receptor
      protein (InsP3R).NCS-1 is known to enhance the activity of InsP3R, and of Ca(2+)
      mediated gamma oscillatory activity in the pedunculopontine nucleus (PPN), part
      of theRAS This study aimed to determine the nature of some of the intracellular
      mechanisms of Li(+)on ratPPNcells and to identify the interaction between
      Li(+)andNCS-1. Since Li(+)has been shown to act by inhibiting the enhancing
      effects ofNCS-1, we tested the hypothesis that Li(+)would reduced the effects of
      overexpression ofNCS-1 and prevent the downregulation of gamma band activity.
      Li(+)decreased gamma oscillation frequency and amplitude by downregulating
      Ca(2+)channel activity, whereasNCS-1 reduced the effect of Li(+)on
      Ca(2+)currents. These effects were mediated by a G-protein overinhibition of
      Ca(2+)currents. These results suggest that Li(+)affected intracellular pathways
      involving the activation of voltage-gated Ca(2+)channels mediated by an
      intracellular mechanism involving voltage-dependent activation of G proteins,
      thereby normalizing gamma band oscillations mediated by P/Q-type calcium channels
      modulated byNCS-1. 

PMID- 27033454
TI  - Ovarian cancer stem-like cells differentiate into endothelial cells and
      participate in tumor angiogenesis through autocrine CCL5 signaling.
AB  - Cancer stem cells (CSCs) are well known for their self-regeneration and
      tumorigenesis potential. In addition, the multi-differentiation potential of CSCs
      has become a popular issue and continues to attract increased research attention.
      Recent studies demonstrated that CSCs are able to differentiate into functional
      endothelial cells and participate in tumor angiogenesis. In this study, we found
      that ovarian cancer stem-like cells (CSLCs) activate the NF-kappaB and STAT3
      signal pathways through autocrine CCL5 signaling and mediate their own
      differentiation into endothelial cells (ECs). Our data demonstrate that CSLCs
      differentiate into ECs morphologically and functionally. Anti-CCL5 antibodies and
      CCL5-shRNA lead to markedly inhibit EC differentiation and the tube formation of
      CSLCs, both in vitro and in vivo. Recombinant human-CCL5 significantly promotes
      ovarian CSLCs that differentiate into ECs and form microtube network. The CCL5
      mediated EC differentiation of CSLCs depends on binding to receptors, such as
      CCR1, CCR3, and CCR5. The results demonstrated that CCL5-CCR1/CCR3/CCR5 activates
      the NF-kappaB and STAT3 signal pathways, subsequently mediating the
      differentiation of CSLCs into ECs. Therefore, this study was conducted based on
      the theory that CSCs improve tumor angiogenesis and provides a novel strategy for
      anti-angiogenesis in ovarian cancer.

PMID- 27033455
TI  - Scinderin promotes the invasion and metastasis of gastric cancer cells and
      predicts the outcome of patients.
AB  - Invasion and metastasis are major malignant characteristics of human gastric
      cancer (GC), but the underlying molecular mechanisms are poorly understood.
      Recent studies have shown that scinderin (SCIN), an actin severing and capping
      protein that regulates the actin cytoskeleton, is involved in the proliferation
      and migration of certain cancer cells. Accordingly, this study aimed to
      investigate the potential role of SCIN in the invasion and metastasis of human GC
      cells and to evaluate its prognostic value for GC patients. We found that high
      levels of SCIN expression in GC tumors were correlated with poor overall survival
      of patients. Silencing of SCIN effectively suppressed the migratory and invasive
      capabilities of human GC cells in vitro and tumorigenicity and metastasis in
      vivo. Furthermore, knockdown of SCIN markedly inhibited the formation of
      filopodia, decreasing GC cell migration and the expression of Cdc42, an important
      regulator of filopodia by GC cells. These findings suggest that SCIN may be a
      novel prognostic marker and a potential therapeutic target in human GC.

PMID- 27033456
TI  - The phytoestrogen genistein enhances multidrug resistance in breast cancer cell
      lines by translational regulation of ABC transporters.
AB  - Breast cancer is the most frequent malignancy in women. Multidrug resistance due
      to overexpression of ABC drug transporters is a common cause of chemotherapy
      failure and disease recurrence. Genistein (GNT) is a phytoestrogen present in
      soybeans and hormone supplements. We investigated the effect of GNT on the
      expression and function of ABC transporters in MCF-7 and MDA-MB-231 breast cancer
      cell lines. Results demonstrated an induction at the protein level of ABCC1 and
      ABCG2 and of ABCC1 in MCF-7 and MDA-MB-231, respectively. MCF-7 cells showed a
      concomitant increase in doxorubicin and mitoxantrone efflux and resistance,
      dependent on ABCG2 activity. ABCC1 induction by GNT in MDA-MB-231 cells modified
      neither drug efflux nor chemoresistance due to simultaneous acute inhibition of
      the transporter activity by GNT. All inductions took place at the translational
      level, as no increment in mRNA was observed and protein increase was prevented by
      cycloheximide. miR-181a, already demonstrated to inhibit ABCG2 translation, was
      down-regulated by GNT, explaining translational induction. Effects were
      independent of classical estrogen receptors. Results suggest potential nutrient
      drug interactions that could threaten chemotherapy efficacy, especially in ABCG2
      expressing tumors treated with substrates of this transporter.

PMID- 27033457
TI  - Affinity purification lipase from wheat germ: comparison of hydrophobic and metal
      chelation effect.
AB  - Cryogels are used quite a lot nowadays for adsorption studies as synthetic
      adsorbents. In this study, lipase enzyme (obtained from Candida cylindracea)
      adsorption capacity of poly(2-hydroxyethyl methacrylate-N-methacryloyl-L
      tryptophan), poly(HEMA-MATrp), and Cu(II) ions immobilized poly(HEMA-MATrp),
      poly(HEMA-MATrp)-Cu(II), cryogel membranes were synthesized to determine and
      compare the adsorption behavior of lipase enzyme. In this regard, the effect of
      pH, interaction time, lipase initial concentration, temperature and ionic
      strength on the adsorption capacity of these membranes was investigated. Maximum
      lipase enzyme adsorption capacities of poly(HEMA-MATrp) and poly(HEMA-MATrp)
      Cu(II) cryogel membranes were determined as 166.4 mg/g and 196.4 mg/g,
      respectively.

PMID- 27033458
TI  - VEGF121 and VEGF165 differentially promote vessel maturation and tumor growth in
      mice and humans.
AB  - Tumor angiogenesis depends on the vascular endothelial growth factor (VEGF),
      which exists in multiple splicing isoforms, including the most abundant VEGF165
      and VEGF121. We have previously shown that the differential capacity of these two
      VEGF isoforms to bind Neuropilin-1 accounts for their diverse ability to recruit
      Nrp1-expressing monocytes (NEMs), resulting in a different arteriogenic
      potential. Here we measure the expression of VEGF165 and VEGF121 in human cancer
      and their influence on tumor growth and vascularization. We measured the
      expression levels of VEGF165 and VEGF121 in human colorectal cancer and found
      that VEGF121 was more expressed than VEGF165, particularly in patients with
      extensive lymph node infiltration. Overexpressing either VEGF165 or VEGF121 in a
      cancer mouse model, we observed that the former decreased, whereas the latter
      increased tumor growth. In both clinical and experimental tumors, VEGF165
      expression resulted in the recruitment of NEMs, paralleled by maturation of the
      tumor vascular network. Finally, hypoxia induced a shift toward the VEGF165
      isoform in the central core of human cancers, as well as in various types of
      cultured cells. These results demonstrate that the two VEGF splicing isoforms are
      differentially expressed in colorectal cancers, exerting opposite effects on
      tumor growth and vessel maturation.

PMID- 27033459
TI  - Development of novel strontium containing bioactive glass based calcium phosphate
      cement.
AB  - OBJECTIVE: The aim of this study was to investigate the effect on properties of
      increasing strontium substitution for calcium in bioactive glasses used as
      precursors for novel calcium phosphate cements. METHODS: Glasses were produced by
      progressively substituting strontium for calcium. Cements were prepared by mixing
      the glass powder with Ca(H2PO4)2 powder with a 2.5% solution of Na2HPO4. Setting
      times and compressive strength were measured after 1h, 1 day, 7 days and 28 days
      immersion in Tris buffer solution. X-ray diffraction (XRD), Fourier transform
      infrared spectroscopy and radiopacity were measured and crystal morphology was
      assessed using scanning electron microscopy. RESULTS: A correlation between the
      phases formed, morphology of the crystallites, setting time and compressive
      strength were analyzed. Setting time increased proportionally with strontium
      substitution in the glass up to 25%, whereas for higher substitutions it
      decreased. Compressive strength showed a maximum value of 12.5MPa and was
      strongly influenced by the interlocking of the crystals and their morphology. XRD
      showed that the presence of strontium influenced the crystal phases formed.
      Octacalcium phosphate (Ca8H2(PO4)6.5H2O, OCP) was the main phase present after 1h
      and 1 day whereas after 28 days OCP was completely transformed to strontium
      containing hydroxyapatite (SrxCa(10-x)(PO4)6(OH)2, SrHA). Radiopacity increased
      proportionally to strontium substitution in the glass. SIGNIFICANCE: A novel
      method to develop a bone substitute forming in vitro SrHA as a final product by
      using a bioactive glass as a precursor was shown. These novel injectable
      bioactive glass cements are promising materials for dental and orthopedic
      applications. Further in vivo characterizations are being conducted.

PMID- 27033460
TI  - Two-body wear rate of PEEK, CAD/CAM resin composite and PMMA: Effect of specimen
      geometries, antagonist materials and test set-up configuration.
AB  - OBJECTIVE: To test and compare the two-body wear rate of three CAD/CAM polymer
      materials and the influence of specimen geometry, antagonist material and test
      set-up configuration. METHODS: Three CAD/CAM polymeric materials were assessed: a
      thermoplastic polyetheretherketone (PEEK), an experimental nanohybrid composite
      (COMP) and a PMMA-based material (PMMA). Crown-shaped and flat specimens were
      prepared from each material. The specimens underwent thermo-mechanical loading
      (50N, 5/55 degrees C; 600,000 chewing cycles) opposed to human enamel and
      stainless steel antagonists. Half of the specimens of each group were loaded with
      a sliding movement of 0.7mm, the remaining half without. Thereby, 24 different
      test set-ups were investigated (n=12). Wear of the materials and antagonists was
      evaluated with a match-3D procedure. The topography of all surfaces was examined
      with scanning electron microscopy (SEM). Data were statistically evaluated with
      four-/one-way ANOVA followed by Scheffe post hoc test and unpaired t-test
      (p<0.05). RESULTS: All PEEK specimens showed significantly less material loss
      than COMP and PMMA specimens when loaded laterally. Within the axial loaded
      groups this was only true for the flat specimens tested with enamel antagonists.
      Crown specimens of these groups exhibited lower loss values than flat ones.
      Lateral force application led mostly to significantly higher material loss than
      the axial load application. On the antagonist side, no impact of CAD/CAM polymer
      material, antagonist material, force application and specimen geometry was found.
      SIGNIFICANCE: Wear of PEEK was lower than that of the resin-based materials when
      lateral forces were applied, but showed comparable antagonist wear rates at the
      same time.

PMID- 27033461
TI  - Anatomic variations of popliteal artery: Evaluation with 128-section CT
      angiography in 1261 lower limbs.
AB  - PURPOSE: The purpose of this study was to evaluate the variations in popliteal
      artery branching in a large population on computed tomography angiography (CTA)
      using a 128-section configuration. MATERIALS AND METHODS: A total of 652 patients
      (532 men, 120 women) with a mean age of 61.7+/-18.1 (SD) years (range: 11-93
      years) who had CTA of the lower limbs with a total of 1261 lower limbs (bilateral
      limbs in 609 patients, unilateral limb in 43 patients) were retrospectively
      included. CTA images were reviewed for popliteal artery branching and possible
      variations. RESULTS: The usual pattern of popliteal artery branching was observed
      in 1118 limbs (88.7%) (type IA) whereas branching variations without the usual
      pattern were found in 143 limbs (11.3%). Forty limbs (3.2%) were categorized as
      type I with non-classical patterns. Forty limbs (3.2%) showed type II high-level
      bifurcation and 63 limbs (4.9%) showed type III aplasia or hypoplasia. The type
      IIC pattern was not observed. Importantly, one single case considered as
      hypoplasia of the peroneal artery and another case identified with a long
      tibioperoneal artery were categorized into new subgroups. CONCLUSIONS:
      Recognizing and evaluating variations in popliteal artery branches is important
      in terms of vascular surgery approaches and interventional vascular procedures.
      CTA is an effective screening method to show the vascular frame of lower
      extremities and variations of popliteal artery. Our study allowed identifying two
      new branching patterns of the popliteal artery not previously described in the
      literature.

PMID- 27033462
TI  - Right ventricular systolic function in heart failure: A long story but still the
      same question.

PMID- 27033463
TI  - Triple antioxidant SNEDDS formulation with enhanced oral bioavailability:
      Implication of chemoprevention of breast cancer.
AB  - The present study aimed to develop quercetin, resveratrol and genistein loaded
      self-nanoemulsifying drug delivery system (SNEDDS) by QbD approach in order to
      improve their oral bioavailability and antioxidant potential. The size and PDI of
      the optimized formulation were found to be <200nm and <0.3, respectively. DPPH
      scavenging assay showed comparable antioxidant activity of antioxidant loaded
      SNEDDS to free antioxidants combination. Furthermore, coumarin-6 loaded SNEDDS
      formulation showed rapid internalization within 1h of incubation by Caco-2 cells.
      Moreover, the pharmacokinetic studies in rats for the optimized formulation and
      free antioxidant suspension were performed. SNEDDS have significantly increased
      the Cmax and area under curve (AUC) of all three antioxidants. The SNEDDS
      demonstrated ~4.27 fold enhancement in oral bioavailability of quercetin, ~1.5
      fold in case of resveratrol and ~2.8 fold in case of genistein as compared to
      free antioxidants suspension. Finally, the prophylactic antitumor efficacy of
      developed formulation was tested against DMBA induced breast cancer model in
      rats, which demonstrated enhanced abeyance towards the tumor growth as compared
      to free antioxidants.

PMID- 27033464
TI  - AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against
      ischemic memory improving cutaneous wound healing.
AB  - Peripheral vasculopathies cause severe wound hypoxia inducing the hypoxamiR miR
      210. High level of miR-210, persisting in wound-edge tissue as ischemic memory,
      suppresses oxidative metabolism and inhibits cell proliferation necessary for
      healing. In wound-edge tissue of chronic wound patients, elevated miR-210 was
      tightly associated with inhibition of epidermal cell proliferation as evident by
      lowered Ki67 immunoreactivity. To inhibit miR-210 in murine ischemic wound-edge
      tissue, we report the formulation of antihypoxamiR functionalized gramicidin
      lipid nanoparticles (AFGLN). A single intradermal delivery of AFGLN encapsulating
      LNA-conjugated anti-hypoximiR-210 (AFGLNmiR-210) lowered miR-210 level in the
      ischemic wound-edge tissue. In repTOPTMmitoIRE mice, AFGLNmiR-210 rescued
      keratinocyte proliferation as visualized by in vivo imaging system (IVIS). 31P
      NMR studies showed elevated ATP content at the ischemic wound-edge tissue
      following AFGLNmiR-210 treatment indicating recovering bioenergetics necessary
      for healing. Consistently, AFGLNmiR-210 improved ischemic wound closure. The
      nanoparticle based approach reported herein is effective for miR-directed wound
      therapeutics warranting further translational development.

PMID- 27033465
TI  - The modulation of haemolymph arginine kinase on the extracellular ATP induced
      bactericidal immune responses in the Pacific oyster Crassostrea gigas.
AB  - Arginine kinase is an important phosphagen kinase (PK) which plays an essential
      role in ATP buffering systems in invertebrates. In the present study, an arginine
      kinase (designated CgAK) was isolated by the lipopolysaccharide (LPS) affinity
      chromatography from the haemolymph of Crassostrea gigas. CgAK could directly bind
      to LPS in a concentration-dependent manner with the dissociation constant (Kd) of
      2.46 * 10(-6) M. The interaction with LPS significantly decreased the ATP
      hydrolytic activity of CgAK, which in turn lead to the accumulation of ATP in
      vitro. The extracellular ATP stimulation could induce Ca(2+) influx, reactive
      oxygen species (ROS) production, and the release of lysosomal enzyme in the
      cellular immune response. In addition, ATP stimulation provoked the bactericidal
      activity towards Escherichia coli, and the scavenging ROS with N-acetyl-l
      cysteine (NAC) abrogated the bactericidal activity, indicating that ATP
      stimulation could induce ROS-dependent antimicrobial activity in haemocytes.
      Collectively, the results demonstrated that the haemolymph CgAK could serve as an
      important purinergic regulator to modulate extracellular ATP, which might further
      have an important effect on the purinergic signaling-activated innate immune
      response of oyster. 

PMID- 27033466
TI  - Molecular characterization of a novel nitric oxide synthase gene from Portunus
      trituberculatus and the roles of NO/O2(-)- generating and antioxidant systems in
      host immune responses to Hematodinium.
AB  - Increasing evidences have established that the nitric oxide synthase (NOS) and
      NADPH oxidase (NOX) play important roles in host defense system by catalyzing the
      production of nitrogen oxide (NO) and superoxide anions (O2(-)), respectively.
      While, there are limited studies to explore the roles of NOS/NOX enzymes in
      crustacean immunity, and no studies as yet were attempted to elucidate their
      functions in host immune responses to parasites. In the present study, we cloned
      a full-length cDNA of NOS and two partial cDNA fragments of NOX and GPx from the
      economic valuable crab Portunus trituberculatus. The full-length cDNA of NOS was
      4002 bp in length that encoded 1203 amino acids containing motifs of the NOS
      protein and conserved domains. The phylogenetic analysis showed that the NOS
      protein sequence was clustered together with those of crustacean species in the
      phylogenetic tree. All of the three novel genes showed high mRNA transcripts in
      the immune-related tissues (e.g. hemocytes, hepatopancreas) of P.
      trituberculatus. Striking fluctuation in the transcripts of the critical NO/O2(-)
      generating/scavenging related genes (NOS, NOX, CuZnSOD, CAT, GPx) as well as in
      the enzymatic activities of NOS, NOX, SOD, CAT and GPx were observed in the
      hemocytes and hepatopancreas of P. trituberculatus post challenged with the
      parasitic dinoflagellate Hematodinium, indicating that the NO/O2(-)- generating
      and the antioxidant systems played vital roles in the crustacean innate immunity
      against the parasitic intrusion. The results indicated a novel respect of the
      host-parasite interaction between the crab host and the parasitic dinoflagellate
      Hematodinium.

PMID- 27033467
TI  - Antimicrobial peptide, hdMolluscidin, purified from the gill of the abalone,
      Haliotis discus.
AB  - A 4.7 kDa antimicrobial peptide was purified from the acidified gill extract of
      the Abalone, Haliotis discus, by cation-exchange and C18 reversed-phase high
      performance liquid chromatography (HPLC). Comparison of the amino acid sequences
      and molecular weight of this peptide with those of other known antimicrobial
      peptides revealed that this antimicrobial peptide have high sequence homology
      with that of cgMolluscidin and was designated hdMolluscidin. hdMolluscidin is
      composed of 46 amino acid residues containing several dibasic residue repeats
      like KK or K-R. hdMolluscidin showed potent antimicrobial activity against both
      Gram-positive bacteria including Bacillus subtilis and Staphylococcus aureus
      (minimal effective concentrations [MECs]; 0.8-19.0 MUg/mL) and Gram-negative
      bacteria including Aeromonas hydrophila, Escherichia coli, Pseudomonas
      aeruginosa, Salmonella enterica, Shigella flexneri, and Vibrio parahemolyticus
      ([MECs]; 1.0-4.0 MUg/mL) without hemolytic activity. However, hdMolluscidin did
      not show any significant activity against Candida albicans. The secondary
      structural prediction suggested that hdMolluscidin might not form an ordered or
      an amphipathic structure. hdMolluscidin did not show membrane permeabilization or
      leakage ability. The full-length hdMolluscidin cDNA contained 566-bp, including a
      5'-untranslated region (UTR) of 63-bp, a 3'-UTR of 359-bp, and an open reading
      frame of 144-bp encoding 47 amino acids (containing Met). cDNA study of
      hdMolluscidin suggests that it is expressed as a mature peptide. Our results
      indicate that hdMolluscidin could relate to the innate immune defenses in abalone
      and it may not act directly on bacterial membrane.

PMID- 27033468
TI  - Copper-induced oxidative damage to the prophenoloxidase-activating system in the
      freshwater crayfish Procambarus clarkii.
AB  - Previous studies have demonstrated copper-induced proteins damage in gill and
      hepatopancreas of the freshwater crayfish Procambarus clarkii, but little
      information is available about its effects on key component of the innate defense
      in haemolymph. In the present study, we evaluated the relationship between
      oxidative carbonylation and prophenoloxidase-activating system (proPO-AS)
      activity, by exposing P. clarkii to sub-lethal concentrations (1/50, 1/12, 1/6
      and 1/3 of the 96 h LC50) Cu(2+) up to 96 h. Six biomarkers of oxidative stress,
      i.e. reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT),
      protein carbonyl (PC), malondialdehyde (MDA) and DNA-protein crosslinks (DPCs),
      and six indicators of immune status, i.e. total hemocyte counts (THCs),
      differential hemocyte counts (DHCs), hemocyanin (HC), prophenoloxidase (proPO),
      serine protease (SP) and phenoloxidase (PO), were determined in haemolymph. The
      results indicated that there was a significant increase (P < 0.05) in the levels
      of ROS, PC, MDA and DPCs accompanied by markedly decreased (P < 0.05) activities
      of proPO, SP, PO and HC in a dose and time dependent manner. The significant and
      positive correlations (P < 0.01) between ROS production and the formation of PC,
      MDA and DPCs were observed in crayfish at 96 h. There was a significant negative
      correlation (P < 0.01) between the levels of protein carbonyls and the activities
      of proPO and SP in hemocyte lysate supernatant and PO and HC in haemolymph.
      Carbonylated proteins may be recognized not merely as a specific signal in
      oxidative stress pathways but also as a "non-self" molecule in proPO-AS. In
      crayfish species, copper-catalyzed protein carbonylation may be one of the main
      mechanisms for immunity dysfunction in proPO-AS.

PMID- 27033469
TI  - Identification and characterization of transforming growth factor beta-activated
      kinase 1 from Litopenaeus vannamei involved in anti-bacterial host defense.
AB  - LvTAK1, a member of transforming growth factor beta-activated kinase 1 (TAK1)
      families, has been identified from Litopenaeus vannamei in this study. The full
      length of LvTAK1 is 2670 bp, including a 2277 bp open reading frame (ORF) that
      encoded a putative protein of 758 amino acids with a calculated molecular weight
      of ~83.4 kDa LvTAK1 expression was most abundant in muscles and was up-regulated
      in gills after LPS, Vibrio parahaemolyticus, Staphylococcus aureus, Poly (I:C)
      and WSSV challenge. Both in vivo and in vitro experiments indicated that LvTAK1
      could activate the expression of several antimicrobial peptide genes (AMPs). In
      addition, the dsRNA-mediated knockdown of LvTAK1 enhanced the susceptibility of
      shrimps to Vibrio parahaemolyticus, a kind of Gram-negative bacteria. These
      results suggested LvTAK1 played important roles in anti-bacterial infection. CoIP
      and subcellular localization assay demonstrated that LvTAK1 could interact with
      its binding protein LvTAB2, a key component of IMD pathway. Moreover, over
      expression of LvTAK1 in Drosophila S2 cell could strongly induce the promoter
      activity of Diptericin (Dpt), a typical AMP which is used to read out of the
      activation of IMD pathway. These findings suggested that LvTAK1 could function as
      a component of IMD pathway. Interestingly, with the over-expression of LvTAK1 in
      S2 cell, the promoter activity of Metchnikowin (Mtk), a main target gene of
      Toll/Dif pathway, was up-regulated over 30 times, suggesting that LvTAK1 may also
      take part in signal transduction of the Toll pathway. In conclusion, we provided
      some evidences that the involvement of LvTAK1 in the regulation of both Toll and
      IMD pathways, as well as innate immune against bacterial infection in shrimp.

PMID- 27033470
TI  - Impact of date palm fruits extracts and probiotic enriched diet on antioxidant
      status, innate immune response and immune-related gene expression of European
      seabass (Dicentrarchus labrax).
AB  - The application of additives in the diet as plants or extracts of plants as
      natural and innocuous compounds has potential in aquaculture as an alternative to
      antibiotics and immunoprophylactics. The aim of the current study was to evaluate
      the potential effects of dietary supplementation of date palm fruit extracts
      alone or in combination with Pdp11 probiotic on serum antioxidant status, on the
      humoral and cellular innate immune status, as well as, on the expression levels
      of some immune-related genes in head-kidney and gut of European sea bass
      (Dicentrarchus labrax) after 2 and 4 weeks of administration. This study showed
      for the first time in European sea bass an immunostimulation in several of the
      parameters evaluated in fish fed with date palm fruits extracts enriched diet or
      fed with this substance in combination with Pdp 11 probiotic, mainly after 4
      weeks of treatment. In the same way, dietary supplementation of mixture diet has
      positive effects on the expression levels of immune-related genes, chiefly in
      head-kidney of Dicentrarchus labrax. Therefore, the combination of both could be
      considered of great interest as potential additives for farmed fish. 

PMID- 27033471
TI  - Accelerated MRI for the assessment of cardiac function.
AB  - Heart disease is a worldwide public health problem; assessment of cardiac
      function is an important part of the diagnosis and management of heart disease.
      MRI of the heart can provide clinically useful information on cardiac function,
      although it is still not routinely used in clinical practice, in part because of
      limited imaging speed. New accelerated methods for performing cardiovascular MRI
      (CMR) have the potential to provide both increased imaging speed and robustness
      to CMR, as well as access to increased functional information. In this review, we
      will briefly discuss the main methods currently employed to accelerate CMR
      methods, such as parallel imaging, k-t undersampling and compressed sensing, as
      well as new approaches that extend the idea of compressed sensing and exploit
      sparsity to provide richer information of potential use in clinical practice. 

PMID- 27033472
TI  - Iron chelation in the treatment of neurodegenerative diseases.
AB  - Disturbance of cerebral iron regulation is almost universal in neurodegenerative
      disorders. There is a growing body of evidence that increased iron deposits may
      contribute to degenerative changes. Thus, the effect of iron chelation therapy
      has been investigated in many neurological disorders including rare genetic
      syndromes with neurodegeneration with brain iron accumulation as well as common
      sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple
      sclerosis. This review summarizes recent advances in understanding the role of
      iron in the etiology of neurodegeneration. Outcomes of studies investigating the
      effect of iron chelation therapy in neurodegenerative disorders are
      systematically presented in tables. Iron chelators, particularly the blood brain
      barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in
      areas with abnormally high concentrations as documented by MRI. Yet, currently,
      there is no compelling evidence of the clinical effect of iron removal therapy on
      any neurological disorder. However, several studies indicate that it may prevent
      or slow down disease progression of several disorders such as aceruloplasminemia,
      pantothenate kinase-associated neurodegeneration or Parkinson's disease.

PMID- 27033473
TI  - Transcatheter arterial chemical infusion for advanced non-small-cell lung cancer:
      long-term outcome and predictor of survival.
AB  - PURPOSE: To evaluate the long-term outcome and the predictor of survival in
      patients treated with transcatheter arterial chemical infusion for advanced non
      small-cell lung cancer (NSCLC). MATERIALS AND METHODS: From May 2008 to August
      2014, a total of 40 consecutive patients with advanced NSCLC who underwent
      transcatheter arterial chemical infusion were enrolled in this retrospective
      study. Data on patients' characteristics, treatment response and follow-up were
      collected and analyzed. RESULTS: A total of 142 cycles of transcatheter arterial
      chemical infusion were administered to the 40 patients (3.55 cycles per case). In
      21 patients, only the bronchial artery was the tumor feeding artery, while in the
      remaining 19 patients, other arteries in addition to the bronchial artery served
      as the tumor feeding arteries. Five patients underwent bronchial arterial
      embolization after transcatheter arterial chemical infusion. There was no serious
      procedure-related complication. During 1-60 months (mean 11.5 +/- 10.0 months)
      follow-up, 33 patients died. The objective response and disease control rates
      were 32.5 and 92.5 %, respectively. The mean time to tumor progression and
      overall survival was 9.2 +/- 1.4 and 13.1 +/- 2.0 months, respectively. Based on
      univariate and multivariate analyses, the independent predictors of decreasing
      overall survival were airway, esophagus, or superior vena cava involvement (P =
      0.037) and more tumor feeding arteries in addition to the bronchial artery (P =
      0.003). CONCLUSION: Transcatheter arterial chemical infusion is an easy and
      effective method for treating patients with advanced NSCLC and it can provide a
      favorable long-term outcome.

PMID- 27033476
TI  - Hard Times.

PMID- 27033474
TI  - Comparison of retrospective PET and MRI-DWI (PET/MRI-DWI) image fusion with
      PET/CT and MRI-DWI in detection of cervical and endometrial cancer lymph node
      metastases.
AB  - OBJECTIVES: The aim of this study was to compare the accuracy of retrospective
      image fusion of PET/MRI-DWI with that of PET/CT and MRI-DWI alone in detecting
      metastatic lymph nodes in patients with cervical and endometrial carcinoma.
      MATERIALS AND METHODS: Twenty-seven patients with endometrial (n = 14) and
      cervical (n = 13) cancer who had undergone preoperative MRI-DWI and PET/CT for
      staging were retrospectively evaluated. The accuracy, sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of PET/CT,
      MRI-DWI, and PET/MRI-DWI image fusion were calculated on a per-patient basis and
      on a per-node basis. Histopathological and follow-up imaging results were used as
      the gold standard. RESULTS: On a per-patient basis PET/MRI-DWI had the same
      sensitivity (87.5 %), specificity (84.2 %), diagnostic accuracy (85.1 %), PPV (70
      %), and NPV (94.1 %) as PET-CT, but on a per-node basis PET/MRI-DWI showed better
      sensitivity (89 vs 70.2 %), specificity (91.6 vs 90.5 %), diagnostic accuracy
      (91.2 vs 87 %), PPV (68.7 vs 60.4 %), and NPV (97.6 vs 93.6 %) than PET-CT.
      Comparison of the areas under the ROC curves for the detection of metastatic
      lymph nodes demonstrated a non-significant difference (p = 0.055) between PET/CT
      and fused PET/MRI-DWI. CONCLUSION: PET/MRI-DWI may be a valuable technique for N
      staging patients with endometrial and cervical cancer, but more studies are
      needed to investigate its potential clinical utility.

PMID- 27033475
TI  - Factors associated with breast screening radiologists' annual mammogram reading
      volume in Italy.
AB  - PURPOSE: Screening mammogram reading volume (SMRV) and total (screening and
      clinical) mammogram reading volume (TMRV) per year are strongly associated with
      the radiologist's diagnostic performance in breast cancer screening. The current
      article reports the prevalence and correlates of a SMRV and a TMRV >=5000 among
      Italian breast screening radiologists. MATERIALS AND METHODS: A questionnaire
      survey was carried out in 2013-2014 by the Italian Group for Mammography
      Screening (GISMa). The questionnaire included items of information for
      radiologist's experience-related characteristics and for facility-level factors
      supposedly associated with SMRV and TMRV. Multivariate analysis was performed
      using backward stepwise multiple logistic regression models. RESULTS: Data for
      235 radiologists from 51 local screening programmes were received. Of the 222
      radiologists who were eligible, 133 (59.9 %) reported a SMRV >=5000 and 163 (73.4
      %) a TMRV >=5000. Multivariate factors positively associated with both
      characteristics included: the number of years of experience reading mammograms;
      the percentage of total working time dedicated to breast imaging and breast care;
      the participation in diagnostic assessment; and the availability of digital
      tomosynthesis at facility. Full-time dedication to breast imaging and breast care
      was associated with the highest odds ratio for a SMRV and a TMRV >=5000, i.e.
      11.80 and 46.74, respectively, versus a percentage of time <=50 %. An early
      (<2000) year of implementation of the screening programme and the availability of
      vacuum-assisted biopsy at facility were associated with a SMRV and, respectively,
      a TMRV >=5000. CONCLUSIONS: Increasing the proportion of radiologists with full
      time dedication to breast imaging and breast care qualified as the most effective
      approach to improve SMRV and TMRV.

PMID- 27033477
TI  - The dangers of NSAIDs: look both ways.

PMID- 27033478
TI  - Damaged doctors: it's time for a binding covenant of care between the NHS and its
      doctors.

PMID- 27033479
TI  - Accelerate, Coordinate, Evaluate Programme: a new approach to cancer diagnosis.

PMID- 27033480
TI  - Bright young things.

PMID- 27033481
TI  - Asthma overdiagnosed in the Netherlands.

PMID- 27033482
TI  - Obstructive sleep apnoea.

PMID- 27033483
TI  - Lack of a RCGP Research Committee.

PMID- 27033484
TI  - Discontinuation of benzodiazepines.

PMID- 27033485
TI  - Viewpoint: The politicisation of a generation.

PMID- 27033486
TI  - Inadequate glycaemic control in LMIC: health system failures in Peru.

PMID- 27033487
TI  - Asylum seekers with complex needs: an enhanced role for primary care specialists?

PMID- 27033489
TI  - Houldsworth Centre, Lanarkshire, Scotland: a new civic facility.

PMID- 27033488
TI  - Yonder: Rosacea, youth mental health, diagnosing arthritis, and telephone triage.

PMID- 27033490
TI  - The coffee-shop model.

PMID- 27033491
TI  - Dangerous Ideas: SAPC competition winner!

PMID- 27033497
TI  - Film: The Closer We Get.

PMID- 27033498
TI  - Back to the future in general practice.

PMID- 27033499
TI  - Patient- and carer-held health records: can they improve annual health checks for
      patients with learning disability?

PMID- 27033500
TI  - Where now for proteinuria testing in chronic kidney disease?: Good evidence can
      clarify a potentially confusing message.

PMID- 27033501
TI  - Guillain-Barre syndrome in general practice: clinical features suggestive of
      early diagnosis.

PMID- 27033502
TI  - Multiple drug-intolerant hypertension: a case series utilising a novel-treatment
      algorithm.

PMID- 27033503
TI  - Building the House of Care for people with long-term conditions: the foundation
      of the House of Care framework.

PMID- 27033504
TI  - Health-Related Quality of Life of Children with Asthma: Self and Parental
      Perceptions.
AB  - PURPOSE: This study aimed to explore whether age, gender, asthma severity, asthma
      duration, and exposure to parental smoking were associated with levels of asthma
      specific health-related quality of life (HRQoL) among Greek children with asthma
      and to identify any differences between self- and proxy ratings of asthma
      specific HRQoL. METHOD: One hundred and seventy-three (173) children with asthma
      (8-12 years old) and their parents completed the Pediatric Quality of Life Asthma
      Module self- and proxy measures. RESULTS: Asthma severity, age, and asthma
      duration explained almost half of the variance in asthma-specific HRQoL scores
      according to self- and proxy reports. Older male children with more severe asthma
      who were diagnosed for a longer period of time and had at least one smoking
      parent reported lower asthma-specific HRQoL according to self- and proxy reports.
      Although children and their parents seemed to agree in their views of asthma
      specific HRQoL, there were significant differences in ratings of specific
      parameters of asthma-specific HRQoL. CONCLUSION: This study identifies the
      factors that account for a significant variance in asthma-specific HRQoL scores
      according to self- and proxy reports and is among the first to record the effect
      of parental smoking on children's and parents' perceptions of asthma-specific
      HRQoL.

PMID- 27033505
TI  - Impact of clinical pharmacy services in a short stay unit of a hospital emergency
      department in Qatar.
AB  - Background The presence of a clinical pharmacist in a hospital's Emergency
      Department (ED) is important to decrease the potential for medication errors. To
      our knowledge, no previous studies have been conducted to evaluate the impact of
      implementing clinical pharmacy services in the ED in Qatar. Objective To
      characterize the contributions of clinical pharmacists in a short stay unit of ED
      in order to implement and scale-up the service to all ED areas in the future.
      Methods A retrospective study conducted for 7 months in the ED of Hamad General
      Hospital, Qatar. The intervention recommendations were made by clinical
      pharmacists to the physician in charge during medical rounds. Results A total of
      824 documented pharmacist recommendations were analyzed. The interventions
      included the following: Providing information to the physician (24.4 %) and
      recommending medication discontinuation (22.0 %), dose adjustment (19.3 %),
      medication addition (16.0 %), changes in frequency of medications (7.6 %),
      medication resumption (5.7 %), and patient education (5.0 %). Conclusion Clinical
      pharmacists in the ED studied play an important role in patient care. 

PMID- 27033506
TI  - Nutraceuticals as Lipid-Lowering Treatment in Pregnancy and Their Effects on the
      Metabolic Syndrome.
AB  - Maternal nutrition and lifestyle before and during pregnancy influence both
      mother and offspring's health and can be correlated with the metabolic syndrome
      in later life. Findings from animal and human studies indicate that nutrition
      during pregnancy has an important role in microbiological, metabolic, physiologic
      and immunologic development and homeostasis. A low nutritional intake in early
      pregnancy may represent a risk for adverse effects during pregnancy as well as on
      birth outcome. It seems that dietary supplementation with probiotics in perinatal
      period may represent safe and practical approach in dealing with the most common
      adverse pregnancy outcomes such as obesity and gestational diabetes. The SPRING
      (Study of Probiotics in the prevention of Gestational diabetes) will give
      important answers about potential benefits of probiotics in pregnant women who
      are obese and overweight and otherwise at the high risk for complications during
      pregnancy. Fish oil supplementation during the last trimester of pregnancy showed
      no effects on plasma lipids and lipoproteins in offspring, as well as on their
      adiposity. The effect of hypercholesterolemia during pregnancy on both mothers
      and child needs to be further investigated as it could have a biological role.
      The guidelines for the eventual clinical approach currently do not exist.
      Potential benefits of nutraceuticals on several metabolic parameters have been
      suggested. Limited evidence does not allow to draw final conclusions on
      preventive health strategies and dietary patterns that should be promoted during
      pregnancy. Further prospective and intervention studies are needed to establish
      it. Healthy lifestyle and dietary advice with appropriate supplements usage
      should be considered. 

PMID- 27033507
TI  - Prospects of Nanocarriers for Oral Delivery of Bioactives Using Targeting
      Strategies.
AB  - The oral route is the preferred mode of administration, however the poor
      intestinal absorption of many bioactive compounds limit their efficacy. Several
      strategies have been developed to overcome the low oral bioavailability of
      bioactive compounds. Nanocarriers present a unique opportunity to overcome this
      limitation due to their diverse bioactive carriage potential, surface
      functionality and design flexibility. Despite these favorable characteristics,
      the oral delivery of nanocarriers faces several challenges which are discussed in
      this review. The review addresses the different mechanisms of transport across
      the intestinal epithelium. In addition, we will comment on the various methods
      and models for evaluating the intestinal permeability, with a critical discussion
      of the uniformity of these models in investigating the oral bioavailability of
      nanocarrier systems. Finally, we will discuss some of the recently developed
      nanocarriers for oral delivery of bioactives that show promising results. 

PMID- 27033508
TI  - Janus Nano- and Microparticles as Smart Drug Delivery Systems.
AB  - Research has been lately prospering in the field of Janus nanoparticles, focusing
      on new synthesis techniques and their application in various fields. This is due
      to the unique characteristics possessed by this type of particles such as their
      anisotropic nature, and their synergistic potential for combination therapy in
      addition to the multilevel targeting. These unique features are essential in
      several biomedical applications, especially the controlled drug delivery. Various
      techniques have been used for the synthesis of Janus nanoparticles including;
      masking, self-assembly, microfluidic and phase separation. They are all aiming at
      production of uniformly sized Janus particles with spatially separated
      functionalities. Herein, the main synthesis approaches of various Janus
      nanoparticles are briefly reviewed with the provision of examples of studies
      focusing on the potential applications of Janus particles in controlled drug
      delivery. 

PMID- 27033509
TI  - Lipid-based siRNA Delivery Systems: Challenges, Promises and Solutions Along the
      Long Journey.
AB  - RNA interference (RNAi) is an evolutionary conserved highly specific gene
      silencing mechanism initiated by small interfering RNA (siRNA) molecules. Fast
      paced preclinical and clinical studies helped the siRNA technology become an
      efficient tool for undruggable targets in different diseases including genetic
      diseases, viral diseases and cancer. Despite great feature of siRNAs that can
      down-regulate any protein in the cells, the full potential and the success of the
      preclinical studies could not be translated into largely successful clinical
      outcomes. It has become clear that the possibility of overcoming the pitfalls for
      in vivo siRNA therapy fully depends on delivery systems. In this review, we start
      with the challenges and barriers for in vivo siRNA delivery. Then we briefly
      discuss the recent developments in siRNA modification technology. We specifically
      focused on siRNA lipidation and delivery approaches with special emphasis on the
      lipid based hybrid systems. Here we summarize the journey of lipid-based micelle
      like nanoparticle systems that combine longevity in blood, effective cellular
      uptake and endosomal escape for successful siRNA delivery and discuss the
      multifunctional stimuli-sensitive systems based on lipids as the next generation
      smart systems. 

PMID- 27033510
TI  - Nucleic-Acid Delivery Using Lipid Nanocapsules.
AB  - Lipid nanocapsules (LNCs) were designed more than 15 years ago to deliver
      lipophilic drugs to cells with non toxic excipients by mimicking lipoproteins.
      During the last 5 years these promising nanocarriers were re-designed to deliver
      nucleic acids to cancer cells. This short review sums up the features of LNCs and
      describes how DNAs or RNAs can be associated or encapsulated in these lipid
      carriers. The results of transfection effects on cells in vitro or in vivo are
      also presented. These new therapeutic strategies have been mainly proposed for
      glioma and melanoma treatment because these cancers are characterized by multiple
      acquired resistances, which can be reversed by DNA transfection or siRNA
      interference as it is discussed in this paper. In conclusion, LNCs are very good
      candidates to deliver nucleic acids to cells in the course of anti-cancer
      therapies. 

PMID- 27033512
TI  - Biopharmaceutical Potential of Two Ramalina Lichens and their Metabolites.
AB  - This paper studies the phytochemical analysis of the acetone extracts of the
      Ramalina fraxinea and Ramalina fastigiata lichens and the antioxidant,
      antimicrobial and antitumour activities of these species and their constituents.
      The phytochemical analysis of two Ramalina species was evaluated using HPLC-UV
      test. The depsides (evernic acid, obtusatic acid, sekikaic acid and atranorin),
      depsidones (protocetraric acid) and dibenzofurane (usnic acid) were identified
      from these lichens. Antioxidant activity was evaluated by DPPH assay, reducing
      power assay and by measuring the amounts of total phenolics in extracts.
      Antimicrobial activity was tested towards five bacterial and 10 fungal species,
      using broth microdilution method to determine the minimum inhibitory
      concentration. Cytotoxic activity was tested using MTT method on the human
      epithelial carcinoma (Hela), human lung carcinoma (A549) and human colon
      carcinoma (LS174) cells. As a result of the study, tested samples showed strong
      free radical scavenging activity with I50 values within the range of 285.45
      423.51 MUg/mL. Absorbance for reducing power was found to be from 0.0043 to
      0.1747. The total amount of phenol concentrations in extracts of Ramalina
      fraxinea and Ramalina fastigiata was 32.63 and 33.49 MUg PE/mg, respectively.
      Methyl evernate showed the strongest antimicrobial properties with the least
      measured MIC value being 0.125 mg/mL. In addition, all samples exhibited strong
      anticancer activities against tested cells (I50 values were between 24.63 and
      161.37 MUg/mL). These results indicate that lichen appears to be a possible
      natural biopharmaceutical. 

PMID- 27033511
TI  - Characterization of Pharmaceutical IgG and Biosimilars Using Miniaturized
      Platforms and LC-MS/MS.
AB  - Therapeutic monoclonal antibodies (mAbs) have made a tremendous impact in
      treating patients with various diseases. MAbs are designed to specifically target
      a cell and illicit a response from the immune system to destroy the cell. As
      originator mAb drug patents are coming to an end, generic pharmaceutical
      companies are poised to replicate and produce so-called biosimilar drugs. MAbs
      are significantly more complicated than small drugs to analyze and produce. The
      mAb proteoform and glycoform must be as similar to the original drug as possible
      to be a viable replacement. The mAb proteoform is well characterized but can be
      altered through various undesirable reactions such as deamidation. The mAb
      glycoform is harder to replicate as the glycan formation is a complicated
      templateless one; it is proving difficult for the originator companies to produce
      a homogenous population of mAbs from batch to batch. Severe side-effects have
      occurred in patients taking mAbs with immunogenic glycans, highlighting the
      importance of quality control mechanisms. The complex nature of mAbs requires
      sensitive and robust tools amenable to the highthroughput analysis required by a
      manufacturing setting. Miniaturized analytical platforms for complex biosimilar
      analysis are still in their infancy but have shown great promise for sample
      preparation. Capillary electrophoresis-laser induced fluorescence remains a
      powerful and fast technique for routine glycan analysis. Mass spectrometry is the
      method of choice for the analysis of mAb proteoforms and is emerging as a
      powerful tool for glycoform analysis. 

PMID- 27033513
TI  - Synergistic Combination of Doxorubicin and Paclitaxel Delivered by Blood Brain
      Barrier and Glioma Cells Dual Targeting Liposomes for Chemotherapy of Brain
      Glioma.
AB  - Brain glioma has become a great threat to human health in decades. To maximize
      the therapeutic efficacy of brain glioma as well as minimize the side effects,
      drugs should be penetrated through the blood brain barrier (BBB) and then
      targeted to the brain carcinoma cells with effective concentration. A dual-ligand
      delivery strategy was employed to achieve both of these goals. Herein, both
      specific targeting ligand transferrin and cell-penetrating peptide TAT were
      conjugated onto liposomes (TF/TAT-LP) to develop a brain glioma dual-ligand
      delivery system. Synergistic combination of doxorubicin (DOX) and paclitaxel
      (PTX), compared with using them separately, could more efficiently suppress tumor
      aggravation. In vitro studies including cellular uptake and three-dimensional
      (3D) tumor spheroid penetration assays proved that TF/TAT-LP could target brain
      endothelial and carcinoma cells with deeply penetration through the endothelial
      monolayers and target to the core of the tumor spheroids. In vivo imaging proved
      that the TF/TAT-LP possesses the highest tumor distribution, which was also
      confirmed by fluorescent images of the brain section. Ultimately, the DOX and PTX
      loaded TF/TAT-LP (TF/TAT-PTX/DOX-LP) shows the best anti-glioma effect with
      improvement of glioma bearing survival time. In conclusion, synergistic
      combination of doxorubicin and paclitaxel delivered by the TF/TAT-LP could
      efficiently target to the brain glioma with satisfying treatment efficiency,
      which may be a promising formulation for glioma therapy. 

PMID- 27033514
TI  - Synthesis of Iron Oxide Micro and Nanoparticles from Aluminum Industry Waste and
      Its Application in the Decolorization of Reactive Blue 235 Dye.
AB  - Iron oxide micro and nanoparticles were successfully synthesized from Red Mud
      (RM) using a simple twostep process. RM was characterized using various
      techniques such as X-Ray Diffractometer (XRD), Fourier Transform- Infra Red
      (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray
      (EDX) analysis and Carbon Hydrogen Nitrogen (CHN) microanalysis. Red mud derived
      iron oxide micro and nanoparticles (RIMNP) were characterized using techniques
      such as XRD, FTIR, SEM/EDX, Transmission Electron Microscopy (TEM) and Vibrating
      Sample Magnetometry (VSM). RIMNP were employed as a Fenton like catalyst for the
      decolorization of a commonly used textile dye Reactive Blue 235 (RB235) from
      aqueous solution. The dynamical data obtained at different concentrations of
      RIMNP fit well with pseudo-second-order kinetic model and 100% dye removal
      efficiency was obtained at 200 mg L-1 concentration of RIMNP. 

PMID- 27033515
TI  - Spatial attention can be biased towards an expected dimension.
AB  - A commonly held view in both exogenous and endogenous orienting is that spatial
      attention is associated with enhanced processing of all stimuli at the attended
      location. However, we often search for a specific target at a particular
      location, so an observer should be able to jointly specify the target identity
      and expected location. Whether attention can bias dimension-specific processes at
      a particular location is not yet clear. We used a dual task to examine the
      effects of endogenous spatial cues on the accuracy of perceptual judgments of
      different dimensions. Participants responded to a motion target and a colour
      target, presented at the same or different locations. We manipulated a central
      cue to predict the location of the motion or colour target. While overall
      performance in the two tasks was comparable, cueing effects were larger for the
      target whose location was predicted by the cue, implying that when attending a
      particular location, processing of the likely dimension was preferentially
      enhanced. Additionally, an asymmetry between the motion and colour tasks was
      seen; motion was modulated by attention, and colour was not. We conclude that
      attention has some ability to select a dimension at a particular location,
      indicating integration of spatial and feature-based attention. 

PMID- 27033516
TI  - Characterization of the prokaryotic diversity through a stratigraphic permafrost
      core profile from the Qinghai-Tibet Plateau.
AB  - Permafrost on the Qinghai-Tibet Plateau is one of the most sensitive regions to
      climate warming, thus characterizing its microbial diversity and community
      composition may be important for understanding their potential responses to
      climate changes. Here, we investigated the prokaryotic diversity in a 10-m-long
      permafrost core from the Qinghai-Tibet Plateau by restriction fragment length
      polymorphism analysis targeting the 16S rRNA gene. We detected 191 and 17
      bacterial and archaeal phylotypes representing 14 and 2 distinct phyla,
      respectively. Proteobacteria was the dominant bacterial phylum, while archaeal
      communities were characterized by a preponderance of Thaumarchaeota. Some of
      prokaryotic phylotypes were closely related to characterized species involved in
      carbon and nitrogen cycles, including nitrogen fixation, methane oxidation and
      nitrification. However, the majority of the phylotypes were only distantly
      related to known taxa at order or species level, suggesting the potential of
      novel diversity. Additionally, both bacterial alpha diversity and community
      composition changed significantly with sampling depth, where these communities
      mainly distributed according to core horizons. Arthrobacter-related phylotypes
      presented at high relative abundance in two active layer soils, while the deeper
      permafrost soils were dominated by Psychrobacter-related clones. Changes in
      bacterial community composition were correlated with most measured soil
      variables, such as carbon and nitrogen contents, pH, and conductivity. 

PMID- 27033517
TI  - Sng1 associates with Nce102 to regulate the yeast Pkh-Ypk signalling module in
      response to sphingolipid status.
AB  - All cells are delimited by biological membranes, which are consequently a primary
      target of stress-induced damage. Cold alters membrane functionality by decreasing
      lipid fluidity and the activity of membrane proteins. In Saccharomyces
      cerevisiae, evidence links sphingolipid homeostasis and membrane phospholipid
      asymmetry to the activity of the Ypk1/2 proteins, the yeast orthologous of the
      mammalian SGK1-3 kinases. Their regulation is mediated by different protein
      kinases, including the PDK1 orthologous Pkh1/2p, and requires the function of
      protein effectors, among them Nce102p, a component of the sphingolipid sensor
      machinery. Nevertheless, the mechanisms and the actors involved in Pkh/Ypk
      regulation remain poorly defined. Here, we demonstrate that Sng1, a transmembrane
      protein, is an effector of the Pkh/Ypk module and identify the phospholipid
      asymmetry as key for yeast cold adaptation. Overexpression of SNG1 impairs
      phospholipid flipping, reduces reactive oxygen species (ROS) and improves, in a
      Pkh-dependent manner, yeast growth in myriocin-treated cells, suggesting that
      excess Sng1p stimulates the Pkh/Ypk signalling. Furthermore, we link these
      effects to the association of Sng1p with Nce102p. Indeed, we found that Sng1p
      interacts with Nce102p both physically and genetically. Moreover, mutant nce102?
      sng1? cells show features of impaired Pkh/Ypk signalling, including increased ROS
      accumulation, reduced life span and defects in Pkh/Ypk-controlled regulatory
      pathways. Finally, myriocin-induced hyperphosphorylation of Ypk1p and Orm2p,
      which controls sphingolipid homeostasis, does not occur in nce102? sng1? cells.
      Hence, both Nce102p and Sng1p participate in a regulatory circuit that controls
      the activity of the Pkh/Ypk module and their function is required in response to
      sphingolipid status. 

PMID- 27033518
TI  - The multifaceted roles of the invariant chain CD74--More than just a chaperone.
AB  - The invariant chain (CD74) is well known for its essential role in antigen
      presentation by mediating assembly and subcellular trafficking of the MHCII
      complex. Beyond this, CD74 has also been implicated in a number of processes
      independent of MHCII. These include the regulation of endosomal trafficking, cell
      migration and cellular signalling as surface receptor of the pro-inflammatory
      cytokine macrophage migration inhibitory factor (MIF). In several forms of
      cancer, CD74 is up-regulated and associated with enhanced proliferation and
      metastatic potential. In this review, an overview of the diverse biological
      functions of the CD74 protein is provided with a particular focus on how these
      may be regulated. In particular, proteolysis of CD74 will be discussed as a
      central mechanism to control the actions of this important protein at different
      levels. 

PMID- 27033520
TI  - Calcium regulation of mitochondrial carriers.
AB  - Mitochondrial function is regulated by calcium. In addition to the long known
      effects of matrix Ca(2+), regulation of metabolite transport by
      extramitochondrial Ca(2+) represents an alternative Ca(2+)-dependent mechanism to
      regulate mitochondrial function. The Ca(2+) regulated mitochondrial transporters
      (CaMCs) are well suited for that role, as they contain long N-terminal extensions
      harboring EF-hand Ca(2+) binding domains facing the intermembrane space. They
      fall in two groups, the aspartate/glutamate exchangers, AGCs, major components of
      the NADH malate aspartate shuttle (MAS) and urea cycle, and the ATP-Mg(2+)/Pi
      exchangers or short CaMCs (APCs or SCaMCs). The AGCs are activated by relatively
      low Ca(2+) levels only slightly higher than resting Ca(2+), whereas all SCaMCs
      studied so far require strong Ca(2+) signals, above micromolar, for activation.
      In addition, AGCs are not strictly Ca(2+) dependent, being active even in Ca(2+)
      free conditions. Thus, AGCs are well suited to respond to small Ca(2+) signals
      and that do not reach mitochondria. In contrast, ATP-Mg(2+)/Pi carriers are
      inactive in Ca(2+) free conditions and activation requires Ca(2+) signals that
      will also activate the calcium uniporter (MCU). By changing the net content of
      adenine nucleotides of the matrix upon activation, SCaMCs regulate the activity
      of the permeability transition pore, and the Ca(2+) retention capacity of
      mitochondria (CRC), two functions synergizing with those of the MCU. The
      different Ca(2+) activation properties of the two CaMCs are discussed in relation
      to their newly obtained structures. This article is part of a Special Issue
      entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and
      Jean-Claude Martinou.

PMID- 27033519
TI  - Oxidative folding in the mitochondrial intermembrane space: A regulated process
      important for cell physiology and disease.
AB  - Mitochondria are fundamental organelles with a complex internal architecture that
      fulfill important diverse functions including iron-sulfur cluster assembly and
      cell respiration. Intense work for more than 30 years has identified the key
      protein import components and the pathways involved in protein targeting and
      assembly. More recently, oxidative folding has been discovered as one important
      mechanism for mitochondrial proteostasis whilst several human disorders have been
      linked to this pathway. We describe the molecular components of this pathway in
      view of their putative redox regulation and we summarize available evidence on
      the connections of these pathways to human disorders.

PMID- 27033521
TI  - Genome-wide screen identifies novel machineries required for both ciliogenesis
      and cell cycle arrest upon serum starvation.
AB  - Biogenesis of the primary cilium, a cellular organelle mediating various
      signaling pathways, is generally coordinated with cell cycle exit/re-entry.
      Although the dynamic cell cycle-associated profile of the primary cilium has been
      largely accepted, the mechanism governing the link between ciliogenesis and cell
      cycle progression has been poorly understood. Using a human genome-wide RNAi
      screen, we identify genes encoding subunits of the spliceosome and proteasome as
      novel regulators of ciliogenesis. We demonstrate that 1) the mRNA processing
      related hits are essential for RNA expression of molecules acting in cilia
      disassembly, such as AURKA and PLK1, and 2) the ubiquitin-proteasome systems
      (UPS)-involved hits are necessary for proteolysis of molecules acting in cilia
      assembly, such as IFT88 and CPAP. In particular, we show that these screen hit
      associated mechanisms are crucial for both cilia assembly and cell cycle arrest
      in response to serum withdrawal. Finally, our data suggest that the mRNA
      processing mechanism may modulate the UPS-dependent decay of cilia assembly
      regulators to control ciliary resorption-coupled cell cycle re-entry. 

PMID- 27033522
TI  - Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein and has
      multiple functions.
AB  - Phosphatidylethanolamine binding proteins (PEBP) represent a superfamily of
      proteins that are conserved from bacteria to humans. In mammals, four members
      have been identified, PEBP1-4. To determine the functional differences among
      PEBP1-4 and the underlying mechanism for their actions, we performed a sequence
      alignment and found that PEBP4 contains a signal peptide and potential
      glycosylation sites, whereas PEBP1-3 are intracellular proteins. To test if PEBP4
      is secreted, we made constructs with Myc epitope at the amino (N) terminus or
      carboxyl (C) terminus to mask the signal sequence or keep it free, respectively.
      Our data revealed that both mouse and human PEBP4 were secreted when the epitope
      was tagged at their C-terminus. To our surprise, secretion was dependent upon the
      C-terminal conserved domain in addition to the N-terminal signal sequence. When
      the epitope was placed to the N-terminus, the recombinant protein failed to
      secrete and instead, was retained in the cytoplasm. Mass spectrometry detected
      asparagine (N)-glycosylation on the secreted PEBP4. Although overexpression of N
      terminal tagged PEBP4 resulted in an inhibition of ERK activation by EGF, that
      with a C-terminal epitope tag did not have such an effect. Likewise, transfection
      of PEBP4 shRNA did not appear to affect ERK activation, suggesting that PEBP4
      does not participate in the regulation of this pathway. In contrast, PEBP4 siRNA
      suppressed phosphorylation of Act at S473. Therefore, our results suggest that
      PEBP4 is a multifunctional protein and can be secreted. It will be important to
      investigate the mechanism by which PEBP4 is secreted and regulates cellular
      events. 

PMID- 27033523
TI  - Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP
      IP5/IP7, not IP6, is essential for virulence.
AB  - Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to
      inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of
      Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the
      kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase
      encoding gene (IPK1) alone (ipk1Delta), and in combination with KCS1
      (ipk1Deltakcs1Delta), profoundly reduced virulence in mice. However, deletion of
      KCS1 and IPK1 had a greater impact on virulence attenuation than that of IPK1
      alone. ipk1Deltakcs1Delta and kcs1Delta lung burdens were also lower than those
      of ipk1Delta. Unlike ipk1Delta, ipk1Deltakcs1Delta and kcs1Delta failed to
      disseminate to the brain. IP profiling confirmed Ipk1 as the major IP5 kinase in
      C. neoformans: ipk1Delta produced no IP6 or PP-IP5/IP7 and, in contrast to
      ipk1Deltakcs1Delta, accumulated IP5 and its pyrophosphorylated PP-IP4 derivative.
      Kcs1 is therefore a dual specificity (IP5 and IP6) kinase producing PP-IP4 and PP
      IP5/IP7. All mutants were similarly attenuated in virulence phenotypes including
      laccase, urease and growth under oxidative/nitrosative stress. Alternative carbon
      source utilisation was also reduced significantly in all mutants except
      ipk1Delta, suggesting that PP-IP4 partially compensates for absent PP-IP5/IP7 in
      ipk1Delta grown under this condition. In conclusion, PP-IP5/IP7, not IP6, is
      essential for fungal virulence. 

PMID- 27033524
TI  - Intestinal transplantation in children: current status.
AB  - Intestinal transplantation (IT) is the least common form of organ
      transplantation; however, it has shown exceptional growth and improvement in
      graft survival rates over the past two decades mainly due to better outcomes
      achieved during the first year of transplantation (76 % at 1 year), due to
      improvement in surgical techniques and the development of better immunosupressive
      therapies as we understand more about the relationship between the recipient and
      host immune system. There are still ongoing issues with chronic rejection and
      long-term survival. Intestinal transplantation is still an acceptable therapy for
      patients with intestinal failure (IF), but it is generally reserved for patients
      who develop severe and life-threatening complications despite standard therapies,
      or those who are not able to maintain a good quality of life. The purpose of this
      review is to describe the current status, indications, outcomes and advances in
      the field of intestinal transplantation. 

PMID- 27033525
TI  - Arborisidine and Arbornamine, Two Monoterpenoid Indole Alkaloids with New
      Polycyclic Carbon-Nitrogen Skeletons Derived from a Common Pericine Precursor.
AB  - Two new monoterpene indole alkaloids, characterized by previously unencountered
      natural product skeletons, viz., arborisidine (1), incorporating indolizidine and
      cyclohexanone moieties fused to an indole unit, and arbornamine (2),
      incorporating an unprecedented 6/5/6/5/6 "arbornane" skeleton (distinct from the
      eburnan or tacaman skeleton), were isolated from a Malayan Kopsia arborea. The
      structures of the alkaloids were determined based on analysis of the NMR and MS
      data. Possible biogenetic pathways to these alkaloids from a common pericine
      precursor (3) are presented. 

PMID- 27033526
TI  - Report on religious slaughter practices in Italy.
AB  - The term 'religious slaughter' commonly refers to the practice of killing animals
      without stunning, according to the precepts of Jewish and Muslim religions. The
      aim of this paper is to assess the situation concerning ritual slaughtering in
      not-stun bovines, small ruminants, and poultry in Italy in 2012. The study was
      divided into 2 phases. During the rst phase, preliminary data about all
      slaughterhouses authorized for ritual slaughter in Italy in 2012 are collected
      through the compilation of a questionnaire sent to each plants. The second step
      involved a sampling of not-stun animals religiously slaughtered in 5 selected
      plants. Authors collected and compiled all informations about management,
      restrain system and rite taking into account in particular animal welfare. 

PMID- 27033527
TI  - Seroprevalence study of the main causes of abortion in dairy cattle in Morocco.
AB  - Sera from 221 cattle were collected in 25 farms in Morocco to investigate the
      evidence and circulation of some of the main bovine abortive agents in the dairy
      cattle farming, where abortions are often reported. All sera were examined for
      brucellosis, 176 for neosporosis, 88 for leptospirosis, and 42 for Bovine viral
      diarrhoea (BVD/MD), Bovine Herpesvirus 1 (BHV-1) (Infectious bovine
      rhinotracheitis, IBR/IPV), and Bovine Herpesvirus 4 (BHV-4) infections (at least
      1 sample per herd). Abortions were reported in 23 (10.4%) of the 221 tested
      cattle. Antibodies against the investigated pathogens were detected in all
      samples tested, with an overall seroprevalence of 33.48% for Brucella, 9.09% for
      Leptospira, 8.52% for Neospora, 37.71% for BVDV, 50% for BHV-1, 9.52% for BHV-4.
      As for Leptospira antibodies against serovars Hardjo, Pomona, and Tarassovi were
      identified. Mixed infections were common. The lack of evidence of non-infectious
      factors epidemiologically related to abortions suggested that the investigated
      agents are to be considered important risk factors in the dynamic of the abortion
      syndrome, even if further investigations are necessary to identify the abortion
      cause. Particular attention should be paid on brucellosis, considering the high
      seroprevalence and its zoonotic relevance.

PMID- 27033528
TI  - Hygienic characteristics and microbiological hazard identification in horse and
      donkey raw milk.
AB  - Today the interest toward horse (Equus caballus) and donkey (Equus asinus) milk
      for human consumption is receiving a renewed attention because of its particular
      composition, hypoallergenicity, and nutraceutical properties. The realistic
      perspective of global use of this aliment in balanced diets, especially for
      infancy and geriatrics, poses the need for a more in depth knowledge on milk
      hygiene and on the health status of dairy animals, as a prerequisite of
      consumers' safety. The aim of this paper was to review the available literature
      on the health and hygiene parameters as well as on the potential microbiological
      hazards in horse and donkey milk and the risks related to their consumption. Both
      microbial contamination and somatic cell count are reasonably low in equine milk
      and also the presence of pathogens, like Escherichia coli O157, Salmonella spp.,
      Campylobacter spp., Yersinia enterocolitica, Brucella spp., Mycobacterium spp.,
      Bacillus cereus, Cronobacter sakazakii, Streptococcus equi subsp. zooepidemicus,
      Rhodococcus equi, Streptococcus dysgalactiae subsp. equisimilis, Clostridium
      difficile and Burkholderia mallei is low. However, in those regions of the world
      where the prevalence of Brucella spp. and Rhodococcus equi is high, the
      alimentary risks could increase. Similarly, in areas with higher incidence of
      immunocompromised people, the increased risks should be warned not only for
      pathogens but also for opportunistic microbiota.

PMID- 27033529
TI  - Magnetic resonance imaging features of progressive ethmoid hematoma in 2 horses.
AB  - Progressive ethmoid hematoma is frequently reported among the pathologies of the
      upper airways in horses. While several hypotheses have been proposed such as
      repeated trauma, inflammatory processes and/or chronic infections, congenital
      phenomena, complication of hemangiomas, and neoplastic processes, the aetiology
      of this condition is yet unknown. Clinical symptoms are non-specific and includes
      haemorrhagic nasal discharge, respiratory noise not related to physical exercise
      and, in most severe cases, phenomena of coughing. The purpose of this case report
      is to contribute to a correct diagnostic approach to this particular pathology of
      upper respiratory tract in horses. Magnetic Resonance allows for a very detailed
      imaging of the development of the disease and suggests appropriate therapeutic
      choices.

PMID- 27033530
TI  - First report of Polycystic kidney disease occurrence in Persian cats in Serbia.
AB  - Polycystic kidney disease (PKD) is an inherited autosomal disorder in cats,
      mostly diagnosed in Persian cats. Renal cysts can be diagnosed by ultrasound, but
      cats must be at least 16 weeks old. The goals of this study were to assess the
      occurrence of PKD in Serbia using a randomly selected group of Persian cats, to
      compare the diagnostic efficacy of ultrasound and genetic tests, and to measure
      haematological and selected biochemical parameters. We examined 70 cats of
      Persian breed, between 4 months and 8 years of age. Complete blood count and
      selected biochemical parameters were measured, renal ultrasound was performed.
      Swabs of the oral cavity were obtained for genetic testing. Percentage of PKD
      positive cats identified by genetic testing was 48.6%, whilst only 18.6% were
      detected through ultrasound. Animals that were polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) positive and ultrasound
      negative ranged from 4 months to 3.5 years. All haematological and biochemical
      parameters were within the the normal range values in all examined cats. Genetic
      methods proved to be the most effective for reliable and early diagnosis of PKD
      in Persian cats. DNA analysis can be used right after birth, and excludes the
      need for other diagnostic procedures, such as ultrasound.

PMID- 27033531
TI  - Canine adenovirus type 1 and Pasteurella pneumotropica co-infection in a puppy.
AB  - In 2008, a 2 months-old male German shepherd was presented with fever,
      depression, and evident organic wasting. The puppy died within 48 hours after the
      onset of clinical signs. A complete necropsy was performed. Bacteriological
      examination of samples from the brain, lung, liver, spleen, and bone marrow
      tested positive for Pasteurella pneumotropica. Histopathology demonstrated
      inflammatory and vascular lesions in the central nervous system and internal
      organs. Canine adenovirus type 1 nucleic acid was detected by polymerase chain
      reaction in the frozen brain but not in the formalin-fixed, paraffin-embedded
      liver and lung samples. The positive PCR was subsequently confirmed by indirect
      fluorescent antibody testing of the paraffin-embedded brain and liver sections.
      Although the liver is the primary site of viral damage, these laboratory findings
      suggest that Canine adenovirus type 1 infection should be included in the
      differential diagnosis of neuropathological diseases in dogs and that adenoviral
      infections could promote septicaemia caused by opportunistic pathogens.

PMID- 27033532
TI  - A promising new ELISA diagnostic test for cattle babesiosis based on Babesia
      bigemina Apical Membrane Antigen-1.
AB  - Babesiosis due to Babesia bigemina is a relevant tick-borne disease, affecting
      cattle worldwide. Many surface proteins of the pathogen including the Apical
      Membrane Antigen 1 (AMA-1) - have been analysed for vaccine and diagnostic
      purposes. This study focused on B. bigemina AMA-1 and on its use for the
      assessment of diagnostic tests. After bioinformatic analyses, AMA-1 codifying
      region was amplified and cloned into an expression vector used to induce protein
      synthesis in Escherichia coli cells. AMA-1 was purified by affinity
      chromatography and used to set up the best condition for an ELISA protocol.
      Bovine field sera positive to B. bigemina were used to evaluate the presence of
      anti-AMA-1 antibodies. In order to verify the assay specificity, sera positive to
      Babesia bovis or to the piroplasm Theileria annulata were also included.
      Significant differences were obtained between sera negative to both B. bigemina
      and B. bovis and samples positive to B. bigemina, to B. bovis or to both
      pathogens. No significant reaction was observed with T. annulata positive sera.
      The results showed that AMA-1 protein is suitable to be used as antigen in
      diagnostic assays for babesiosis diagnosis in cattle, as it does not show any
      cross reaction with anti-T. annulata antibodies.

PMID- 27033533
TI  - Molecular characterization of Leishmania infantum strains by kinetoplast DNA RFLP
      PCR.
AB  - Multilocus enzyme electrophoresis is the tool most frequently used to classify
      Leishmania spp., although it is time consuming and, sometimes, a not enough
      discriminative method. In the present study a kinetoplast DNA polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) was used to
      characterize 16 zymodeme MON-1 Leishmania infantum strains: 15 were from dogs
      housed in public kennels of 7 geographical areas in the Emilia-Romagna region,
      Northern Italy, 1 was the L. infantum reference strain MHOM/TN/1980/IPT1. Six
      enzymatic patterns were observed. Kinetoplast DNA RFLP-PCR confirmed to have a
      good discriminatory power within the same zymodeme and proved to be useful for
      comparing few strains or discriminating between relapse and reinfection in the
      same host. We therefore recommend it use for discriminating between relapse and
      reinfection in the same host rather than supporting large-scale epidemiological
      studies.

PMID- 27033534
TI  - First evidence of West Nile virus lineage 2 circulation in Turkey.
AB  - In August 2014, a West Nile virus (WNV) strain belonging to lineage 2 was
      detected in the brain tissues of a 9 year old mare euthanised after showing
      severe clinical signs in Bursa region, Turkey. Phylogenetic analyses of 290 bp of
      NS3 coding region clustered the Turkish strain together with the 2010-2012 Greek
      isolates. Either IgG and IgM or IgG only WNV antibodies were detected in 2 and 11
      horses, respectively, which were in the outbreak surrounding. No WNV RNA was
      detected in pools of 50 individuals of Culex pipiens (n = 2), Ochlerotatus
      caspius (n = 2), and Culex theileri (n = 1) collected in the infected premises. 

PMID- 27033536
TI  - Very high gravity ethanol and fatty acid production of Zymomonas mobilis without
      amino acid and vitamin.
AB  - Very high gravity (VHG) fermentation is the mainstream technology in ethanol
      industry, which requires the strains be resistant to multiple stresses such as
      high glucose concentration, high ethanol concentration, high temperature and
      harsh acidic conditions. To our knowledge, it was not reported previously that
      any ethanol-producing microbe showed a high performance in VHG fermentations
      without amino acid and vitamin. Here we demonstrate the engineering of a xylose
      utilizing recombinant Zymomonas mobilis for VHG ethanol fermentations. The
      recombinant strain can produce ethanol up to 136 g/L without amino acid and
      vitamin with a theoretical yield of 90 %, which is significantly superior to that
      produced by all the reported ethanol-producing strains. The intracellular fatty
      acids of the bacterial were about 16 % of the bacterial dry biomass, with the
      ratio of ethanol:fatty acids was about 273:1 (g/g). The recombinant strain was
      achieved by a multivariate-modular strategy tackles with the multiple stresses
      which are closely linked to the ethanol productivity of Z. mobilis. The over
      expression of metB/yfdZ operon enabled the growth of the recombinant Z. mobilis
      in a chemically defined medium without amino acid and vitamin; and the fatty
      acids overproduction significantly increased ethanol tolerance and ethanol
      production. The coupled production of ethanol with fatty acids of the Z. mobilis
      without amino acid and vitamin under VHG fermentation conditions may permit a
      significant reduction of the production cost of ethanol and microbial fatty
      acids.

PMID- 27033535
TI  - Metagenomic analysis of denitrifying wastewater enrichment cultures able to
      transform the explosive, 3-nitro-1,2,4-triazol-5-one (NTO).
AB  - Removal of 3-nitro-1,2,4-triazol-5-one (NTO) was investigated in conjunction with
      heterotrophic and autotrophic denitrifying growth conditions by a microbial
      consortium from a wastewater treatment plant. Microcosms were supplemented with
      molasses, methanol, or thiosulfate. Cultures were passaged twice by transferring
      10 % of the culture volume to fresh media on days 11 and 21. Rates of NTO removal
      were 18.71 +/- 0.65, 9.04 +/- 2.61, and 4.34 +/- 2.72 mg/L/day while rates of
      nitrate removal were 20.08 +/- 1.13, 21.58 +/- 1.20, and 24.84 +/- 1.26 mg/L/day,
      respectively, for molasses, methanol, or thiosulfate. Metagenomic analysis showed
      that Proteobacteria and Firmicutes were the major phyla in the microbial
      communities. In molasses supplemented cultures, the community profile at the
      family level changed over time with Pseudomonadaceae the most abundant (67.4 %)
      at day 11, Clostridiaceae (65.7 %) at day 21, and Sporolactobacillaceae (35.4 %)
      and Clostridiaceae (41.0 %) at day 29. Pseudomonadaceae was the dominant family
      in methanol and thiosulfate supplemented cultures from day 21 to 29 with 76.6 and
      81.6 % relative abundance, respectively.

PMID- 27033537
TI  - A novel conditional gene silencing method using a tumor-specific and heat
      inducible siRNA system.
AB  - RNAi technology is an invaluable tool for investigating gene function. However,
      the non-temporal and non-spatial control is the primary limitation, which leads
      to siRNA leakiness and off-target effects. In this study, we inserted three kinds
      of HSE into tumor specific promoter hTERT, which aims to construct a temperature
      inducible and tumor-specific RNAi plasmid vector. In our system, the expression
      of mature siRNA is tightly controlled by the heat shock-inducible and tumor
      specific promoters. From the expression level of RNA and protein, we determined
      the efficiency of the inducible siRNA system by targeting SNCG gene in HepG2 and
      MCF-7 cells. Results showed that the controllable siRNA system could be induced
      to initiate siRNA expression by heat-induce. The silencing effect of SNCG is on a
      relative low level (10 %) at 37  degrees C, while it is significantly increased
      to 50 or 60 % after heat inducing at 43  degrees C. This new conditional siRNA
      system provides a novel approach to drive the siRNA expression by heat-inducible
      and tumor-specific promoter.

PMID- 27033538
TI  - Characterization of aspartate kinase and homoserine dehydrogenase from
      Corynebacterium glutamicum IWJ001 and systematic investigation of L-isoleucine
      biosynthesis.
AB  - Previously we have characterized a threonine dehydratase mutant TD(F383V)
      (encoded by ilvA1) and an acetohydroxy acid synthase mutant AHAS(P176S, D426E,
      L575W) (encoded by ilvBN1) in Corynebacterium glutamicum IWJ001, one of the best
      L-isoleucine producing strains. Here, we further characterized an aspartate
      kinase mutant AK(A279T) (encoded by lysC1) and a homoserine dehydrogenase mutant
      HD(G378S) (encoded by hom1) in IWJ001, and analyzed the consequences of all these
      mutant enzymes on amino acids production in the wild type background. In vitro
      enzyme tests confirmed that AK(A279T) is completely resistant to feed-back
      inhibition by L-threonine and L-lysine, and that HD(G378S) is partially resistant
      to L-threonine with the half maximal inhibitory concentration between 12 and 14
      mM. In C. glutamicum ATCC13869, expressing lysC1 alone led to exclusive L-lysine
      accumulation, co-expressing hom1 and thrB1 with lysC1 shifted partial carbon flux
      from L-lysine (decreased by 50.1 %) to L-threonine (4.85 g/L) with minor L
      isoleucine and no L-homoserine accumulation, further co-expressing ilvA1
      completely depleted L-threonine and strongly shifted carbon flux from L-lysine
      (decreased by 83.0 %) to L-isoleucine (3.53 g/L). The results demonstrated the
      strongly feed-back resistant TD(F383V) might be the main driving force for L
      isoleucine over-synthesis in this case, and the partially feed-back resistant
      HD(G378S) might prevent the accumulation of toxic intermediates. Information
      exploited from such mutation-bred production strain would be useful for metabolic
      engineering.

PMID- 27033539
TI  - Masculine norms about emotionality and social constraints in young and older
      adult men with cancer.
AB  - Beliefs that men should restrict their display of emotions, or restrictive
      emotionality, might contribute to adjustment to cancer and this might be
      sensitive to social receptivity to disclosure. The present research examined
      relationships of restrictive emotionality, social constraints, and psychological
      distress in young adults with testicular cancer (N = 171; Study 1) and older men
      with prostate cancer (N = 66; Study 2). Study 1: positive associations were
      observed for social constraints and restrictive emotionality with depressive
      symptoms. Social constraints moderated the relationship, such that high
      restrictive emotionality was associated with higher depressive symptoms in those
      with high constraints. Study 2: only social constraints (and not restrictive
      emotionality) was positively associated with depressive symptoms and cancer
      related intrusive thoughts. The social constraints * restrictive emotionality
      interaction approached significance with depressive symptoms, such with high
      social constraints low restrictive emotionality was associated with higher
      depressive symptoms compared to those with less constraints. No significant
      associations were found for intrusive thoughts in either study. Findings
      demonstrate unique relationships with psychological distress across the lifespan
      of men with cancer given perception of constraints and adherence to masculine
      norms about emotionality.

PMID- 27033540
TI  - Microsleeps are Associated with Stage-2 Sleep Spindles from Hippocampal-Temporal
      Network.
AB  - Behavioral microsleeps are associated with complete disruption of responsiveness
      for [Formula: see text][Formula: see text]s to 15[Formula: see text]s. They can
      result in injury or death, especially in transport and military sectors. In this
      study, EEGs were obtained from five nonsleep-deprived healthy male subjects
      performing a 1[Formula: see text]h 2D tracking task. Microsleeps were detected in
      all subjects. Microsleep-related activities in the EEG were detected,
      characterized, separated from eye closure-related activity, and, via source-space
      independent component analysis and power analysis, the associated sources were
      localized in the brain. Microsleeps were often, but not always, found to be
      associated with strong alpha-band spindles originating bilaterally from the
      anterior temporal gyri and hippocampi. Similarly, theta-related activity was
      identified as originating bilaterally from the frontal-orbital cortex. The alpha
      spindles were similar to sleep spindles in terms of frequency, duration, and
      amplitude-profile, indicating that microsleeps are equivalent to brief instances
      of Stage-2 sleep. 

PMID- 27033541
TI  - AIP mutations in young patients with acromegaly and the Tampico Giant: the
      Mexican experience.
AB  - Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare
      in sporadic acromegaly, their prevalence among young patients is nonnegligible.
      The objectives of this study were to evaluate the frequency of AIP mutations in a
      cohort of Mexican patients with acromegaly with disease onset before the age of
      30 and to search for molecular abnormalities in the AIP gene in teeth obtained
      from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly
      (51 females) with disease onset <30 years was analysed (median age of disease
      onset of 23 years) and correlated with clinical, biochemical and imaging
      characteristics. Sequencing was also carried out in DNA extracted from teeth of
      the Tampico Giant. Five patients (7 %) harboured heterozygous, germline mutations
      of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man
      with symptoms of GH excess since age 14) the c.910C>T (p.Arg304Ter), well-known
      truncating mutation was identified; in one of these two cases and her identical
      twin sister, the mutation proved to be a de novo event, since neither of their
      parents were found to be carriers. In the remaining three patients, new mutations
      were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in
      frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A
      > T, p.Lys290Ter), which are predicted to be pathogenic based on in silico
      analysis. Patients with AIP mutations tended to have an earlier onset of
      acromegaly and harboured larger and more invasive tumours. A previously described
      genetic variant of unknown significance (c.869C > T, p.Ala299Val) was identified
      in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican
      patients with acromegaly is similar to that of European cohorts. Our results
      support the need for genetic evaluation of patients with early onset acromegaly. 

PMID- 27033542
TI  - Impact of vitamin D deficiency on the clinical and biochemical phenotype in women
      with sporadic primary hyperparathyroidism.
AB  - The purpose of the study was to evaluate the relationship between serum 25(OH)D
      and the clinical phenotype in 215 consecutive Italian Caucasian women with
      sporadic primary hyperparathyroidism (PHPT) not taking vitamin D supplements. The
      study was performed at a single Italian tertiary center. PHPT-related
      manifestations, serum 25(OH)D, and other parameters of calcium metabolism and
      bone mineral density (BMD) by DXA were recorded. Serum 25(OH)D was negatively
      correlated with age (r = -0.18; P = 0.006), BMI (r = -0.20; P = 0.002), PTH (r = 
      0.21; P = 0.001), bone-specific alkaline phosphatase (BSAP) (r = -0.27; P <
      0.001), and eGFR (r = -0.22; P = 0.01), and positively with serum creatinine and
      1/3 distal radius BMD (R-BMD; r = 0.17; P = 0.015). In a multivariate regression
      analysis, serum 25(OH)D remained significantly correlated with age (r = -0.18; P
      = 0.005), BMI (r = -0.23; P = 0.049), serum PTH (r = -0.01; P = 0.023), BSAP (r =
      -0.01; P = 0.023) and eGFR (r = -0.09; P = 0.001), but not with R-BMD. Serum
      25(OHD) was higher in patients with nephrolithiasis than in those without
      nephrolithiasis (18.5 +/- 8.8 vs. 15.6 +/- 8.0 ng/ml; P = 0.029), whereas no
      difference was found between fractured and unfractured patients (16.8 +/- 9.3 vs.
      16.0 +/- 7.7; P = 0.663). There was a statistically significant inverse
      correlation between vitamin D status [defined by quartiles of measured values as
      well as commonly accepted cutoffs of serum 25(OH)D] and severity of the disease,
      as reflected by higher PTH and BSAP, but not by meeting the latest guidelines for
      parathyroidectomy. In conclusion, a low vitamin D status is associated with some
      features reflecting a more severe biochemical and clinical phenotype of PHPT in
      Italian women not taking vitamin D supplements.

PMID- 27033543
TI  - Engineering a filamentous fungus for L-rhamnose extraction.
AB  - L-Rhamnose is a high value rare sugar that is used as such or after chemical
      conversions. It is enriched in several biomass fractions such as the pectic
      polysaccharides rhamnogalacturonan I and II and in naringin, hesperidin, rutin,
      quercitrin and ulvan. We engineered the filamentous fungus Aspergillus niger to
      not consume L-rhamnose, while it is still able to produce the enzymes for the
      hydrolysis of L-rhamnose rich biomass. As a result we present a strain that can
      be used for the extraction of L-rhamnose in a consolidated process. In the
      process the biomass is hydrolysed to the monomeric sugars which are consumed by
      the fungus leaving the L-rhamnose. 

PMID- 27033544
TI  - Petroselinic acid purification and its use for the fermentation of new
      sophorolipids.
AB  - Petroselinic acid, a positional isomer of oleic acid, was isolated from the
      vegetable oil of Coriandrum sativum fruits. This uncommon fatty acid was
      subsequently used as substrate for sophorolipid fermentation with a Starmerella
      bombicola lactone esterase overexpression (oe sble) strain. A petroselinic acid
      based diacetylated sophorolipid lactone was obtained in high purity without
      incorporation of de novo synthesized fatty acids such as oleic acid. A total
      production of 40 g/L was obtained. The petroselinic acid based sophorolipid
      lactone was subsequently hydrolyzed towards the petroselinic acid based
      sophorolipid acid. For both compounds, their critical micelle concentration (CMC)
      and corresponding surface tension were compared to their oleic acid based
      counterparts. Both petroselinic acid based sophorolipids displayed a much lower
      CMC value than their oleic acid based counterparts, although their minimal
      surface tension was the same. Besides, the sophorolipid fermentation product was
      chemically modified towards a novel C12 sophorolipid aldehyde. This derivative
      constitutes an interesting building block for further modification towards new-to
      nature sophorolipids with high potential for self-assembly applications. 

PMID- 27033545
TI  - A Case Series: Outcomes of Endoscopic Biliary Self-Expandable Metal Stent for
      Malignant Biliary Obstruction with Surgically Altered Anatomy.
AB  - BACKGROUND: Few studies have reported the outcomes of self-expandable metal stent
      (SEMS) placement for malignant biliary obstruction in patients with surgically
      altered anatomy. AIMS: To evaluate the outcomes of biliary metal stent placement
      with the use of a short-type single-balloon enteroscope (working length, 1520 mm;
      channel diameter, 3.2 mm) in such patients. METHODS: We retrospectively studied
      13 malignant biliary obstructions treated by SEMS placement. Technical success
      rate, functional success rate, time to recurrent biliary obstruction (RBO), and
      complications were evaluated. RESULTS: Technical success rate was 100 % (13/13),
      functional success rate was 92 % (12/13), and the median time to RBO was 247 days
      (95 % CI 205.6-285.5). Complications comprised mild pancreatitis in one patient.
      Uncovered SEMSs were placed in three obstructions, partially covered SEMS in five
      obstructions, and fully covered SEMSs in five obstructions. Three stents occluded
      (two ingrowths and one mucosal hyperplasia), and one symptomatic distal stent
      migration occurred after more than 30 days from placement. CONCLUSIONS: A short
      type single-balloon enteroscope was useful for the placement of various SEMS in
      this patient population with satisfactory outcomes.

PMID- 27033546
TI  - Conformational photoswitching of a synthetic peptide foldamer bound within a
      phospholipid bilayer.
AB  - The dynamic properties of foldamers, synthetic molecules that mimic folded
      biomolecules, have mainly been explored in free solution. We report on the
      design, synthesis, and conformational behavior of photoresponsive foldamers bound
      in a phospholipid bilayer akin to a biological membrane phase. These molecules
      contain a chromophore, which can be switched between two configurations by
      different wavelengths of light, attached to a helical synthetic peptide that both
      promotes membrane insertion and communicates conformational change along its
      length. Light-induced structural changes in the chromophore are translated into
      global conformational changes, which are detected by monitoring the solid-state
      (19)F nuclear magnetic resonance signals of a remote fluorine-containing residue
      located 1 to 2 nanometers away. The behavior of the foldamers in the membrane
      phase is similar to that of analogous compounds in organic solvents. 

PMID- 27033547
TI  - The 3.8 A resolution cryo-EM structure of Zika virus.
AB  - The recent rapid spread of Zika virus and its unexpected linkage to birth defects
      and an autoimmune neurological syndrome have generated worldwide concern. Zika
      virus is a flavivirus like the dengue, yellow fever, and West Nile viruses. We
      present the 3.8 angstrom resolution structure of mature Zika virus, determined by
      cryo-electron microscopy (cryo-EM). The structure of Zika virus is similar to
      other known flavivirus structures, except for the ~10 amino acids that surround
      the Asn(154) glycosylation site in each of the 180 envelope glycoproteins that
      make up the icosahedral shell. The carbohydrate moiety associated with this
      residue, which is recognizable in the cryo-EM electron density, may function as
      an attachment site of the virus to host cells. This region varies not only among
      Zika virus strains but also in other flaviviruses, which suggests that
      differences in this region may influence virus transmission and disease.

PMID- 27033549
TI  - Organocatalyzed atom transfer radical polymerization driven by visible light.
AB  - Atom transfer radical polymerization (ATRP) has become one of the most
      implemented methods for polymer synthesis, owing to impressive control over
      polymer composition and associated properties. However, contamination of the
      polymer by the metal catalyst remains a major limitation. Organic ATRP photoredox
      catalysts have been sought to address this difficult challenge but have not
      achieved the precision performance of metal catalysts. Here, we introduce diaryl
      dihydrophenazines, identified through computationally directed discovery, as a
      class of strongly reducing photoredox catalysts. These catalysts achieve high
      initiator efficiencies through activation by visible light to synthesize polymers
      with tunable molecular weights and low dispersities. 

PMID- 27033548
TI  - Complement and microglia mediate early synapse loss in Alzheimer mouse models.
AB  - Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline.
      Involvement of microglia and complement in AD has been attributed to
      neuroinflammation, prominent late in disease. Here we show in mouse models that
      complement and microglia mediate synaptic loss early in AD. C1q, the initiating
      protein of the classical complement cascade, is increased and associated with
      synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial
      complement receptor CR3 reduces the number of phagocytic microglia, as well as
      the extent of early synapse loss. C1q is necessary for the toxic effects of
      soluble beta-amyloid (Abeta) oligomers on synapses and hippocampal long-term
      potentiation. Finally, microglia in adult brains engulf synaptic material in a
      CR3-dependent process when exposed to soluble Abeta oligomers. Together, these
      findings suggest that the complement-dependent pathway and microglia that prune
      excess synapses in development are inappropriately activated and mediate synapse
      loss in AD. 

PMID- 27033552
TI  - The Impact of Lung Ventilation on Some Cytokines after Coronary Artery Bypass
      Grafting.
AB  - BACKGROUND AND AIMS: Cardiopulmonary bypass induces a systematic inflammatory
      response, which is partly understood by investigation of peripheral blood
      cytokine levels alone; the lungs may interfere with the net cytokine
      concentration. We investigated whether lung ventilation influences lung passage
      of some cytokines after coronary artery bypass grafting. MATERIAL AND METHODS: In
      total, 47 patients undergoing coronary artery bypass grafting were enrolled, and
      37 were randomized according to the ventilation technique: (1) No-ventilation
      group, with intubation tube detached from the ventilator; (2) low tidal volume
      group, with continuous low tidal volume ventilation; and (3) continuous 10 cm H2O
      positive airway pressure. Ten selected patients undergoing surgery without
      cardiopulmonary bypass served as a referral group. Representative pulmonary and
      radial artery blood samples were collected for the evaluation of calculated lung
      passage (pulmonary/radial artery) of the pro-inflammatory cytokines (interleukin
      6 and interleukin 8) and the anti-inflammatory interleukin 10 immediately after
      induction of anesthesia (T1), 1 h after restoring ventilation/return of flow in
      all grafts (T2), and 20 h after restoring ventilation/return of flow in all
      grafts (T3). RESULTS: Pulmonary/radial artery interleukin 6 and pulmonary/radial
      artery interleukin 8 ratios ( p = 0.001 and p = 0.05, respectively) decreased,
      while pulmonary/radial artery interleukin 10 ratio ( p = 0.001) increased in
      patients without cardiopulmonary bypass as compared with patients with
      cardiopulmonary bypass. CONCLUSIONS: The pulmonary/radial artery equation is an
      innovative means for the evaluation of cytokine lung passage after coronary
      artery bypass grafting. The mode of lung ventilation has no impact on some
      cytokines after coronary artery bypass grafting in patients treated with
      cardiopulmonary bypass.

PMID- 27033550
TI  - Spatial sequestration and detoxification of Huntingtin by the ribosome quality
      control complex.
AB  - Huntington disease (HD) is a neurological disorder caused by polyglutamine
      expansions in mutated Huntingtin (mHtt) proteins, rendering them prone to form
      inclusion bodies (IB). We report that in yeast, such IB formation is a factor
      dependent process subjected to age-related decline. A genome-wide, high-content
      imaging approach, identified the E3 ubiquitin ligase, Ltn1 of the ribosome
      quality control complex (RQC) as a key factor required for IB formation,
      ubiquitination, and detoxification of model mHtt. The failure of ltn1? cells to
      manage mHtt was traced to another RQC component, Tae2, and inappropriate control
      of heat shock transcription factor, Hsf1, activity. Moreover, super-resolution
      microscopy revealed that mHtt toxicity in RQC-deficient cells was accompanied by
      multiple mHtt aggregates altering actin cytoskeletal structures and retarding
      endocytosis. The data demonstrates that spatial sequestration of mHtt into IBs is
      policed by the RQC-Hsf1 regulatory system and that such compartmentalization,
      rather than ubiquitination, is key to mHtt detoxification. 

PMID- 27033551
TI  - Altered potassium channel distribution and composition in myelinated axons
      suppresses hyperexcitability following injury.
AB  - Neuropathic pain following peripheral nerve injury is associated with
      hyperexcitability in damaged myelinated sensory axons, which begins to normalise
      over time. We investigated the composition and distribution of shaker-type
      potassium channels (Kv1 channels) within the nodal complex of myelinated axons
      following injury. At the neuroma that forms after damage, expression of Kv1.1 and
      1.2 (normally localised to the juxtaparanode) was markedly decreased. In contrast
      Kv1.4 and 1.6, which were hardly detectable in the naive state, showed increased
      expression within juxtaparanodes and paranodes following injury, both in rats and
      humans. Within the dorsal root (a site remote from injury) we noted a
      redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels
      with alpha-DTX after injury reinstated hyperexcitability of A-fibre axons and
      enhanced mechanosensitivity. Changes in the molecular composition and
      distribution of axonal Kv1 channels, therefore represents a protective mechanism
      to suppress the hyperexcitability of myelinated sensory axons that follows nerve
      injury. 

PMID- 27033553
TI  - AtMYB12 regulates flavonoids accumulation and abiotic stress tolerance in
      transgenic Arabidopsis thaliana.
AB  - In plants, transcriptional regulation is the most important tool for modulating
      flavonoid biosynthesis. The AtMYB12 gene from Arabidopsis thaliana has been shown
      to regulate the expression of key enzyme genes involved in flavonoid
      biosynthesis, leading to the increased accumulation of flavonoids. In this study,
      the codon-optimized AtMYB12 gene was chemically synthesized. Subcellular
      localization analysis in onion epidermal cells indicated that AtMYB12 was
      localized to the nucleus. Its overexpression significantly increased accumulation
      of flavonoids and enhanced salt and drought tolerance in transgenic Arabidopsis
      plants. Real-time quantitative PCR (qRT-PCR) analysis showed that overexpression
      of AtMYB12 resulted in the up-regulation of genes involved in flavonoid
      biosynthesis, abscisic acid (ABA) biosynthesis, proline biosynthesis, stress
      responses and ROS scavenging under salt and drought stresses. Further analyses
      under salt and drought stresses showed significant increases of ABA, proline
      content, superoxide dismutase (SOD) and peroxidase (POD) activities, as well as
      significant reduction of H2O2 and malonaldehyde (MDA) content. The results
      demonstrate the explicit role of AtMYB12 in conferring salt and drought tolerance
      by increasing the levels of flavonoids and ABA in transgenic Arabidopsis. The
      AtMYB12 gene has the potential to be used to enhance tolerance to abiotic
      stresses in plants. 

PMID- 27033554
TI  - Identification of candidate genes for an early-maturing soybean mutant by genome
      resequencing analysis.
AB  - Flowering is indicative of the transition from vegetative to reproductive phase,
      a critical event in the life cycle of plants. In this study, we performed whole
      genome resequencing by Illumina HiSeq to identify changes in flowering genes
      using an early-flowering phenotype of soybean mutant line Josaengserori (JS)
      derived from Korean landrace, Seoritae (SR), and we obtained mapped reads of
      131,769,690 and 167,669,640 bp in JS and SR, respectively. From the whole genome
      sequencing results between JS and SR, we identified 332,821 polymorphic SNPs and
      65,178 indels, respectively. Among these, 30 flowering genes were in SNPs and 25
      were in indels. Among 30 flowering genes detected in SNPs, Glyma02g33040,
      Glyma06g22650, Glyma10g36600, Glyma13g01290, Glyma14g10530, Glyma16g01980,
      Glyma17g11040, Glyma18g53690, and Glyma20g29300 were non-synonymous substitutions
      between JS and SR. Changes in Glyma10g36600 (GI), Glya02g33040 (AGL18),
      Glyma17g11040 (TOC1), and Glyma14g10530 (ELF3) in JS affected the expression of
      GmFT2a and resulted in early flowering. These results provide insight into the
      regulatory pathways of flowering in soybean mutants and help to improve our
      knowledge of soybean mutation breeding. 

PMID- 27033555
TI  - Perceptual versus motor spatiotemporal interactions in duration reproduction
      across two hands.
AB  - The possibility of spatiotemporal interactions in motor action that are
      comparable with the perceptual kappa effect was tested in the present study. In
      the kappa effect, the empty duration between two successive stimuli is
      overestimated when the spatial distance between these stimuli is increased.
      Indeed, when participants reproduced the standard (empty) duration, delivering
      two tactile stimuli to different hands resulted in a longer reproduced duration
      than delivering both stimuli to the same hand, regardless of how long the
      standard was. However, when a spatial factor during motor action (reproduction)
      was manipulated by letting participants use an identical hand or different hands
      for two button pushes reproducing the standard, the different-hand condition
      yielded a shorter reproduced duration than the identical-hand condition when the
      standard was 1000 ms or more. More specifically, this decrement in the reproduced
      duration grew linearly with the standard, suggesting that a given space increases
      the "rate" of an internal timer during motor action. Because each tick of the
      timer was accelerated, the total error causing an earlier push of the second
      button was increased with the standard. A pacemaker-counter model was adopted to
      explain the differences between the perceptual and the motor spatiotemporal
      interactions. 

PMID- 27033556
TI  - Electroconvulsive therapy for depression in Parkinson's disease: systematic
      review of evidence and recommendations.
AB  - AIM: We performed a systematic review of evidence regarding treatment of
      depression in Parkinson's disease (PD) utilizing electroconvulsive therapy.
      METHODS: The search led to the inclusion of 43 articles, mainly case reports or
      case series, with the largest number of patients totaling 19. RESULTS: The
      analysis included 116 patients with depression and PD; depression improved in
      93.1%. Where motor symptoms' severity was reported, 83% of patients improved.
      Cognition did not worsen in the majority (94%). Many patients experienced
      delirium or transient confusion, sometimes necessitating discontinuation of
      electroconvulsive therapy (ECT). Little is known about maintenance ECT in this
      population. CONCLUSION: ECT can benefit patients suffering from PD and
      depression. We recommend an algorithm for treatment of depression in PD,
      utilizing ECT sooner rather than later.

PMID- 27033557
TI  - Telangiectatic lichen sclerosus on the cheek successfully treated with topical
      tacrolimus.

PMID- 27033558
TI  - Engineering entangled microwave photon states through multiphoton interactions
      between two cavity fields and a superconducting qubit.
AB  - It has been shown that there are not only transverse but also longitudinal
      couplings between microwave fields and a superconducting qubit with broken
      inversion symmetry of the potential energy. Using multiphoton processes induced
      by longitudinal coupling fields and frequency matching conditions, we design a
      universal algorithm to produce arbitrary superpositions of two-mode photon states
      of microwave fields in two separated transmission line resonators, which are
      coupled to a superconducting qubit. Based on our algorithm, we analyze the
      generation of evenly-populated states and NOON states. Compared to other
      proposals with only single-photon process, we provide an efficient way to produce
      entangled microwave photon states when the interactions between superconducting
      qubits and microwave fields are in the strong and ultrastrong regime. 

PMID- 27033559
TI  - Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by
      the mutation and duration of diabetes.
AB  - AIMS/HYPOTHESIS: The finding that patients with diabetes due to potassium channel
      mutations can transfer from insulin to sulfonylureas has revolutionised the
      management of patients with permanent neonatal diabetes. The extent to which the
      in vitro characteristics of the mutation can predict a successful transfer is not
      known. Our aim was to identify factors associated with successful transfer from
      insulin to sulfonylureas in patients with permanent neonatal diabetes due to
      mutations in KCNJ11 (which encodes the inwardly rectifying potassium channel
      Kir6.2). METHODS: We retrospectively analysed clinical data on 127 patients with
      neonatal diabetes due to KCNJ11 mutations who attempted to transfer to
      sulfonylureas. We considered transfer successful when patients completely
      discontinued insulin whilst on sulfonylureas. All unsuccessful transfers received
      >=0.8 mg kg(-1) day(-1) glibenclamide (or the equivalent) for >4 weeks. The in
      vitro response of mutant Kir6.2/SUR1 channels to tolbutamide was assessed in
      Xenopus oocytes. For some specific mutations, not all individuals carrying the
      mutation were able to transfer successfully; we therefore investigated which
      clinical features could predict a successful transfer. RESULTS: In all, 112 out
      of 127 (88%) patients successfully transferred to sulfonylureas from insulin with
      an improvement in HbA1c from 8.2% (66 mmol/mol) on insulin, to 5.9% (41 mmol/mol)
      on sulphonylureas (p = 0.001). The in vitro response of the mutation to
      tolbutamide determined the likelihood of transfer: the extent of tolbutamide
      block was <63% for the p.C166Y, p.I296L, p.L164P or p.T293N mutations, and no
      patients with these mutations successfully transferred. However, most individuals
      with mutations for which tolbutamide block was >73% did transfer successfully.
      The few patients with these mutations who could not transfer had a longer
      duration of diabetes than those who transferred successfully (18.2 vs 3.4 years,
      p = 0.032). There was no difference in pre-transfer HbA1c (p = 0.87), weight-for
      age z scores (SD score; p = 0.12) or sex (p = 0.17). CONCLUSIONS/INTERPRETATION:
      Transfer from insulin is successful for most KCNJ11 patients and is best
      predicted by the in vitro response of the specific mutation and the duration of
      diabetes. Knowledge of the specific mutation and of diabetes duration can help
      predict whether successful transfer to sulfonylureas is likely. This result
      supports the early genetic testing and early treatment of patients with neonatal
      diabetes aged under 6 months.

PMID- 27033560
TI  - Islet-intrinsic effects of CFTR mutation.
AB  - Cystic fibrosis-related diabetes (CFRD) is the most significant extra-pulmonary
      comorbidity in cystic fibrosis (CF) patients, and accelerates lung decline. In
      addition to the traditional view that CFRD is a consequence of fibrotic
      destruction of the pancreas as a whole, emerging evidence may implicate a role
      for cystic fibrosis transmembrane-conductance regulator (CFTR) in the regulation
      of insulin secretion from the pancreatic islet. Impaired first-phase insulin
      responses and glucose homeostasis have also been reported in CF patients. CFTR
      expression in both human and mouse beta cells has been confirmed, and recent
      studies have shown differences in endocrine pancreatic morphology from birth in
      CF. Recent experimental evidence suggests that functional CFTR channels are
      required for insulin exocytosis and the regulation of membrane potential in the
      pancreatic beta cell, which may account for the impairments in insulin secretion
      observed in many CF patients. These novel insights suggest that the pathogenesis
      of CFRD is more complicated than originally thought, with implications for
      diabetes treatment and screening in the CF population. This review summarises
      recent emerging evidence in support of a primary role for endocrine pancreatic
      dysfunction in the development of CFRD. Summary * CF is an autosomal recessive
      disorder caused by mutations in the CFTR gene * The vast majority of morbidity
      and mortality in CF results from lung disease. However CFRD is the largest extra
      pulmonary co-morbidity and rapidly accelerates lung decline * Recent experimental
      evidence shows that functional CFTR channels are required for normal patterns of
      first phase insulin secretion from the pancreatic beta cell * Current clinical
      recommendations suggest that insulin is more effective than oral glucose-lowering
      drugs for the treatment of CFRD. However, the emergence of CFTR corrector and
      potentiator drugs may offer a personalised approach to treating diabetes in the
      CF population.

PMID- 27033562
TI  - Study provides evidence that "vaginal seeding" of infants born by caesarean
      partially restores microbiota.

PMID- 27033561
TI  - Urinary biomarkers are associated with incident cardiovascular disease, all-cause
      mortality and deterioration of kidney function in type 2 diabetic patients with
      microalbuminuria.
AB  - AIMS/HYPOTHESIS: We evaluated two urinary biomarkers reflecting different aspects
      of renal pathophysiology as potential determinants of incident cardiovascular
      disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients
      with type 2 diabetes and microalbuminuria but without clinical features of
      coronary artery disease. METHODS: In a prospective study of 200 patients, all
      received multifactorial treatment. Baseline measurements of urinary hepatocyte
      growth factor (HGF) and adiponectin were available for 191 patients. Cox models
      were adjusted for sex, age, LDL-cholesterol, smoking, HbA1c, plasma creatinine,
      systolic BP and urinary AER (UAER). The pre-defined endpoint of chronic kidney
      disease progression was a decline in the eGFR of >30% during follow-up. HRs per 1
      SD increment of log-transformed values are presented. RESULTS: Patients had a
      mean +/- SD age of 59 +/- 9 years with a median (interquartile range) UAER of 103
      (39-230) mg/24 h. During a median 6.1 years of follow-up, there were 40 incident
      CVD events, 26 deaths and 42 patients reached the pre-defined chronic kidney
      disease progression endpoint after 4.9 years (median). Higher urinary HGF was a
      determinant of CVD in unadjusted (HR 1.9 [95% CI 1.3, 2.8], p = 0.001) and
      adjusted (HR 2.0 [95% CI 1.2, 3.2], p = 0.004) models, and of all-cause mortality
      in unadjusted (HR 2.3 [95% CI 1.3, 3.9], p = 0.003) and adjusted (HR 2.5 [95% CI
      1.3, 4.8], p = 0.005) models. A higher adiponectin level was associated with CVD
      in unadjusted (HR 1.4 [95% CI 1.0, 1.9], p = 0.04) and adjusted (HR 1.4 [95% CI
      1.1, 2.3], p = 0.013) models, and with a decline in the eGFR of >30% in
      unadjusted (HR 1.6 [95% CI 1.2, 2.2], p = 0.008) and adjusted (HR 1.5 [95% CI
      1.1, 2.2], p = 0.007) models. CONCLUSIONS/INTERPRETATION: In patients with type 2
      diabetes and microalbuminuria receiving multifactorial treatment, higher urinary
      HGF was associated with incident CVD and all-cause mortality, and higher
      adiponectin was associated with CVD and deterioration in renal function.

PMID- 27033563
TI  - Quantum oscillations from generic surface Fermi arcs and bulk chiral modes in
      Weyl semimetals.
AB  - We re-examine the question of quantum oscillations from surface Fermi arcs and
      chiral modes in Weyl semimetals. By introducing two tools--semiclassical phase
      space quantization and a numerical implementation of a layered construction of
      Weyl semimetals--we discover several important generalizations to previous
      conclusions that were implicitly tailored to the special case of identical Fermi
      arcs on top and bottom surfaces. We show that the phase-space quantization
      picture fixes an ambiguity in the previously utilized energy-time quantization
      approach and correctly reproduces the numerically calculated quantum oscillations
      for generic Weyl semimetals with distinctly curved Fermi arcs on the two
      surfaces. Based on these methods, we identify a 'magic' magnetic-field angle
      where quantum oscillations become independent of sample thickness, with striking
      experimental implications. We also analyze the stability of these quantum
      oscillations to disorder, and show that the high-field oscillations are expected
      to persist in samples whose thickness parametrically exceeds the quantum mean
      free path.

PMID- 27033564
TI  - The Impact of Information on Doctors' Attitudes Toward Generic Drugs.
AB  - The objective of this study is to assess the impact of information on doctors'
      attitudes and perceptions toward generics. A cross-sectional survey based on a
      specially designed 21-item questionnaire was conducted. The survey involved
      doctors of different specialties working in a public hospital in Greece. The
      analysis includes descriptive and inferential statistics, reliability and
      validity tests, as well as structural equation modeling to evaluate the causal
      model. Statistical analysis was accomplished by using SPSS 20 and Amos 20. A
      total of 134 questionnaires out of 162 were received, providing a response rate
      of 82.71%. A number of significant associations were found between information
      and perceptions about generic medicines with demographic characteristics. It
      seems that the provision of quality information on generic drugs influences
      doctors' attitudes and prescription practices toward generic drugs. This is not a
      static process but a rather dynamic issue involving information provision
      policies for strengthening the proper doctors' attitudes toward generic drugs. 

PMID- 27033565
TI  - Agreement Between HEDIS Performance Assessments in the VA and Medicare Advantage:
      Is Quality in the Eye of the Beholder?
AB  - Medicare Advantage (MA) plans and the Veterans Affairs (VA) health care system
      assess quality of care using standardized Healthcare Effectiveness Data and
      Information Set (HEDIS) performance measures. Little is known, however, about the
      relative accuracy of quality indicators for persons receiving care in more than
      one health care system. Among Veterans dually enrolled in an MA plan, we examined
      the agreement between MA and VA HEDIS assessments. Our study tested the
      hypothesis that private health plans underreport quality of care relative to a
      fully integrated delivery system utilizing a comprehensive electronic health
      record. Despite assessing the same individuals using identical measure
      specifications, reported VA performance was significantly better than reported MA
      performance for all 12 HEDIS measures. The VA's performance advantage ranged from
      9.8% (glycosylated hemoglobin [HbA1c] < 7.0% in diabetes) to 54.7% (blood
      pressure < 140/90 mm Hg in diabetes). The overall agreement between VA and MA
      HEDIS assessments ranged from 38.5% to 62.6%. Performance rates derived from VA
      and MA aggregate data were 1.6% to 14.3% higher than those reported by VA alone.
      This analysis suggests that neither MA plans nor the VA fully capture quality of
      care information for dually enrolled persons. However, the VA's system-wide
      electronic health record may allow for more complete capture of quality
      information across multiple providers and settings. 

PMID- 27033566
TI  - Remarkable reduction of thermal conductivity in phosphorene phononic crystal.
AB  - Phosphorene has received much attention due to its interesting physical and
      chemical properties, and its potential applications such as thermoelectricity. In
      thermoelectric applications, low thermal conductivity is essential for achieving
      a high figure of merit. In this work, we propose to reduce the thermal
      conductivity of phosphorene by adopting the phononic crystal structure,
      phosphorene nanomesh. With equilibrium molecular dynamics simulations, we find
      that the thermal conductivity is remarkably reduced in the phononic crystal. Our
      analysis shows that the reduction is due to the depressed phonon group velocities
      induced by Brillouin zone folding, and the reduced phonon lifetimes in the
      phononic crystal. Interestingly, it is found that the anisotropy ratio of thermal
      conductivity could be tuned by the 'non-square' pores in the phononic crystal, as
      the phonon group velocities in the direction with larger projection of pores is
      more severely suppressed, leading to greater reduction of thermal conductivity in
      this direction. Our work provides deep insight into thermal transport in phononic
      crystals and proposes a new strategy to reduce the thermal conductivity of
      monolayer phosphorene. 

PMID- 27033567
TI  - [Management of chronic rhinosinusitis: on the path to precision medicine].

PMID- 27033568
TI  - [In-vitro study of photodynamic therapy of antibiotic-resistant staphylococcus
      from patients with chronic rhinosinusitis].
AB  - OBJECTIVE: To evaluate the photodynamic therapy (PDT) against multi-antibiotic
      resistant Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis
      (S.epidermidis) obtained from patients with chronic rhinosinusitis (CRS).
      METHODS: Forty-five CRS patients who had been given medical treatment but still
      needed endoscopic surgery were included in this study. The mucus from middle
      meatus was collected from these patients during surgery, followed by separation
      of S. aureus and S. epidermidis and drug sensitive test. The strains which could
      form biofilm were selected. Light emitting diode (LED) array with a major
      wavelength of (633+/-10) nm was used as light source and 5-Aminolevulinic acid
      (ALA) was used as photosensitizer in this PDT experiment. The safe range of LED
      dose and ALA concentration which were not toxic to bacteria by themselves were
      confirmed, and then did PDT experiment on S. aureus and S. epidermidis. The data
      of bacterial colony forming unit were transformed to lgCFU before statistical
      analysis.The Graph Pad Prism 5 software was used to analyzed the data. RESULTS:
      Thirteen S. aureus and 16 S. epidermidis were included in this experiment(from 45
      patients), all of them were multi-antibiotic-resistant bacteria, and four of S.
      aureus and five of S. epidermidis could form biofilm in each group. In planktonic
      S. aureus experiment, the mean lgCFU was 8.32+/-0.31 in control group whereas the
      experiment group was 6.47+/-0.67 (t=9.01, P<0.01), and in planktonic S.
      epidermidis experiment the final data was 8.34+/-0.20 (control group) and 6.97+/
      0.59 (experiment group) (t=8.84, P<0.01). In biofilm S. aureus experiment, the
      mean lgCFU was 8.68+/-0.05 (control group), 6.90+/-0.96(experiment group)
      (t=3.68, P<0.05); and in biofilm S. epidermidis experiment the data was 8.67+/
      0.05 (control group), 7.29+/-0.61 (experiment group, t=5.07, P<0.01). CONCLUSION:
      Our results demonstrated that ALA-mediated PDT on multi-antibiotic-resistant S.
      aureus and S. epidermidis from CRS patients was effective in vitro. Additional
      work defining if the PDT treatment would damage the nasal mucosa and further
      checking the effectiveness of PDT in vivo is still needed.

PMID- 27033569
TI  - [Expression of heme oxygenase-1 in nasal polyps and regulation by
      glucocorticoid].
AB  - OBJECTIVE: To evaluate the expression and possible modulation of heme oxygenase-1
      (HO-1) in nasal polyps of patients with chronic rhinosinusitis with nasal polyps
      (CRSwNP). METHODS: Nasal polyps and uncinate process tissues were collected from
      25 CRSwNP patients and 19 healthy controls with nasal septal deviation. HO-1
      expression was examined using qRT-PCR, immunohistochemistric staining and Western
      blot analysis. Moreover, additional uncinate process mucosal samples of 15
      healthy controls with nasal septal deviation were harvested for nasal explant
      culture experiments. HO-1 expression was measured in cultured nasal explant in
      response to specific inflammatory and glucocorticoid stimulation. SPSS 20.0
      software was used to analyze the data. RESULTS: The mRNA and protein expression
      of HO-1 was significantly increased in polyp tissues, 1.220+/-0.397 in mRNA and
      1.409+/-0.701 in protein, compared with healthy controls 0.464+/-0.318 in mRNA
      and 0.017+/-0.1147 in protein (U=22.00 in mRNA and U=1.00 in protein, both P<
      0.05). The immunohistochemical results showed that HO-1 was mainly distributed in
      the epithelial layer, submucosal glands and inflammatory cells in nasal tissues.
      Nasal explant culture experiments demonstrated that HO-1 mRNA was upregulated by
      IL-17A. The HO-1 mRNA level before the stimulation was 1.000, and 17.264+/-4.275
      after the stimulation of 1 ng/ml IL-17A (U=0, P<0.05), 19.128+/-4.605 after the
      stimulation of 10 ng/ml IL-17A (U=0, P<0.05), but was significantly suppressed
      after stimulation with glucocorticoids (dexamethasone, DEX). The mRNA level after
      the glucocorticoids stimulation was 0.370+/-0.101 (U=0, P<0.05) and 0.316+/-0.167
      (U=0, P<0.05) respectively. Furthermore, the HO-1 mRNA was inhibited by TGF
      beta1, the mRNA level was 0.217+/-0.322 (U=0, P<0.05), 0.070+/-0.070 (U=0,
      P<0.05), respectively. CONCLUSION: Increased HO-1 expression may play a role in
      the pathogenesis of CRSwNP, which may be considered as the therapeutic target.

PMID- 27033570
TI  - [Features of epithelial-to-mesenchymal transition in nasal polyposis].
AB  - OBJECTIVE: To detect the expression of epithelial-to-mesenchymal transition (EMT)
      biomarkers in nasal polyposis (NP) and to determine the effect of transforming
      growth factor beta1 (TGF-beta1) on EMT in cultured nasal epithelial cells.
      METHODS: The specimens were obtained from sinus mucosa of 10 NP patients and
      inferior turbinate mucosa of 10 nasal septum deviation patients. The difference
      of mRNA expression of E-cadherin, beta-catenin , zonula occludens 1 (ZO-1),
      vimentin and alpha-smooth muscle actin (alpha-SMA) in tissue and cultured nasal
      epithelial cells was detected by real-time PCR. The difference of protein
      exprssion of E-cadherin and vimentin in cultured nasal epithelial cells was
      detected by Western blot.SPSS 16.0 software was used to analyze the data.
      RESULTS: The relative expression of E-cadherin and ZO-1 in NP tissues (0.012+/
      0.007; 0.006+/-0.003) was higher than in normal nasal mucosa (0.041+/-0.024;
      0.011+/-0.005), the difference was significant (t=3.675, P<0.01; t=2.956,
      P<0.05). However, there was no significant difference in the relative expression
      of beta-catenin, vimentin and alpha-SMA between two groups (t value was 0.990,
      0.429, 0.326, all P>0.05). In cultured nasal epithelial cells both from two
      groups, TGF-beta1 induced the decreased E-cadherin, ZO-1 (tcontrol value was
      3.639, 3.430, both P<0.05; tNP value was 3.279, 2.864, both P<0.05) and increased
      alpha-SMA, vimentin mRNA expression (tcontrol value was -6.393, -3.085, all
      P<0.05; tNP value was -2.981, -3.087, both P<0.05). Also, TGF-beta1 induced the
      decreased E-cadherin and increased vimentin protein expression (tcontrol value
      was 3.583, -3.844, both P<0.05; tNP value was 5.113, -3.642, both P<0.05).
      CONCLUSION: EMT is likely to contribute to nasal polyposis and TGF-beta1 is
      involved in this process.

PMID- 27033571
TI  - [Cervical esophagostomy improves the life quality of patients with dysphagia
      induced by radiotherapy for nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the effect of cervical esophagostomy for the treatment of
      patients with dysphagia induced by radiotherapy, in order to improve the
      therapeutic effects. METHODS: A retrospective study was performed on 53
      nasopharyngeal carcinoma (NPC) patients with dysphagia, who received cervical
      esophagostomy. The nutritional status of these patients was measured at five
      given time before and after operation. The occurrence of pneumonia and reflux
      esophagitis before and after operation was recorded, and the quality of life
      based on SF-36 quality of life (QOL) scale was studied. RESULTS: After operation,
      the nutritional status of these patients improved substantially, including the
      weight, levels of hemoglobin, total protein, albumin and transferring (P<0.05).
      The pneumonia-infection decreased from 60.38% (32/53) before operation to 15.22%
      (7/46) after operation (chi(2)=21.04, P<0.01). The incidences of reflux
      esophagitis decreased from 26.42% (14/53)without operation to 6.52% (3/46) after
      operation (chi(2)=5.00, P<0.01). Meanwhile, the status of physical health, mental
      health as well as physical function and social function of these patients were
      improved significantly at 1 month, 6 months, 1 year and 2 years after operation
      (P<0.05). CONCLUSION: Cervical esophagostomy can improve the life quality of
      patients with dysphagia induced by radiotherapy for nasopharyngeal carcinoma.

PMID- 27033572
TI  - [Treatment and outcome of recurrent cervical lymph nodes in patients with
      nasopharyngeal carcinoma after radiotherapy].
AB  - OBJECTIVE: To evaluate the efficacies of different treatments for recurrent
      cervical lymph nodes and the factors contributing to prognosis in patients with
      nasopharyngeal carcinoma after radiotherapy. METHODS: Clinical data of 79
      patients with nasopharyngeal carcinoma after radiotherapy were retrospectively
      analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes
      by pathological examination. The factors including sex, age, the interval between
      completion of radiotherapy and recurrence, rN stage, treatment methods, and the
      location relationship between recurrent lesion and primary tumor in the neck were
      analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional
      hazards regression mode were used in the statistical analysis. RESULTS: The
      median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival
      rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode
      analysis indicated that age, rN stage, treatment methods, and the location
      relationship between recurrent lesion and primary tumor were significantly
      prognostic factors. CONCLUSIONS: Neck dissection is superior to re-radiotherapy
      in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after
      radiotherapy. The patients younger than 45 years old, in early rN stage and for
      recurrence in the center region of primary tumor have a better prognosis.

PMID- 27033573
TI  - [miR-140-5p affects the migration and invasion of hypopharyngeal carcinoma cells
      by downregulating ADAM10 expression].
AB  - OBJECTIVE: To investigate the expression of miR-140-5p and ADAM10 in
      hypopharyngeal carcinoma tissues and their effects on the migration and invasion
      of FaDu cells and underlying mechanism. METHODS: The miR-140-5p and ADAM10 mRNA
      levels in 33 cases of hypopharyngeal carcinoma tissues and adjacent normal
      tissues were measured by real-time quantitative polymerase chain reaction (RT
      qPCR). Transwell migration assay and transwell invasion assay were used to test
      the metastasis ability of FaDu cells after upregulation or downregulation of miR
      140-5p and downregulation of ADAM10. The protein expression levels of ADAM10 in
      hypopharyngeal carcinoma tissues and the FaDu cells after transfection were
      determined by Western blot assays. RESULTS: The expression level of miR-140-5p
      was significantly downregulated in hypopharyngeal carcinoma tissues compared with
      adjacent tissues (t=-4.016, P<0.01), which was significantly correlated with
      tumor classification and lymph node metastasis (P<0.05). Conversely, mRNA and
      protein expressions of ADAM10 were significantly upregulated in tumor tissues
      (t=3.960, P<0.01; t=12.089, P<0.01), and were significantly downregulated in the
      FaDu cells after tranfected with si-ADAM10 (t=8.653, P<0.05; t=5.191, P<0.05).
      Transwell assay showed that compare with control group, the migration and
      invasive cells decreased significantly in hsa-mir-140-5p group (t=3.255, P<0.05;
      t=2.942, P<0.05), while increased significantly in anti-hsa-mir-140-5p group, (t=
      13.521, P<0.05; t=-6.223, P<0.05). The migration and invasive cells in si-ADAM10
      group were less than those in control group (t=4.759, P<0.05; t=3.663, P<0.05).
      The downregulation of ADAM10 attenuated the effect of anti-mir-140-5p in FaDu
      cells. Western blot assay showed that ADAM10 expression was apparently decreased
      in hsa-mir-140-5p group and increased in anti-mir-140-5p group compared with
      control group. CONCLUSIONS: The expression of miR-140-5p was significantly
      downregulated in hypopharyngeal carcinoma tissues and correlated with tumor
      classification and lymph node metastasis. ADAM10 was upregulated in tumor
      tissues. MiR-140-5p suppresses the migration and invasion abilities of FaDu
      cells, possibly through downregulation of ADAM10.

PMID- 27033574
TI  - [Effect of CD14 promoter variants on the susceptibility to laryngeal cancer].
AB  - OBJECTIVE: To investigate the effects of -260C>T and -651C>T genetic variants in
      the promoter region of CD14 on the susceptibility to laryngeal cancer. METHODS: A
      total of 163 patients with laryngeal cancer and 326 healthy subjects as controls
      were included. Genotypes of CD14 -260C>T (rs2569190) and -651C>T (rs5744455)
      variants were determined by polymerase chain reaction-based restriction fragment
      length polymorphism (PCR-RFLP). Odd ratios (OR) and 95% confidence intervals
      (95%CI) were calculated with logistic regression analysis. RESULTS: Compared with
      CD14 -651CC genotype carriers, -651TT genotype carriers had the increased risk of
      laryngeal cancer with the OR (95%CI) of 5.79 (2.38-14.11). When the -651TT
      genotype carriers were stratified by smoking status, the OR (95%CI) for laryngeal
      cancer was 8.64 (1.88-39.77) in nonsmokers and 4.74 (1.69-13.25) in smokers; the
      OR (95%CI) was 5.40 (1.10-26.45) in the light smokers and 4.30 (1.10-16.75) in
      the hevey smokers. When the -651TT genotype carriers were stratified by drinking
      status, the OR (95%CI) for laryngeal cancer was 6.48 (2.81-14.95) in nondrinkers
      and 2.01 (0.65-6.26) in drinkers. There was no significant difference in CD14 
      260C>T genotype distribution between patients and controls. CONCLUSION:
      Polymorphisms of -651C>T in CD14 promoter contribute to the susceptibility to
      laryngeal cancer in Chinese population.

PMID- 27033575
TI  - [A novel technique for simultaneous multi-gene mutation screening in 225 patients
      with nonsyndromic hearing loss].
AB  - OBJECTIVE: Using simultaneous multi-gene mutation screening to investigate the
      new method molecular epidemiological basis of 225 patients with nonsyndromic
      hearing loss in Tianjin, and verifying the for simultaneous multi-gene mutation
      screening. METHODS: Two hundred and twenty-five patients with severe non
      syndromic deafness from Tianjin CDPF and Association of the Deaf were included in
      the study. The single nucleotide polymorphisms scan, (SNPscan) technique was used
      for screening the 115 spots mutations in three common deafness-related genes
      (GJB2, SLC26A4, mtDNA 12S rRNA) of patients with nonsyndromic hearing loss in
      Tianjin. We verified the results by Sanger sequencing. RESULTS: Among the 225
      patients, there were 111 cases of deafness caused by mutation (49.3%). Using this
      method, up to 50% of the patients in our study were identified to have hereditary
      HL caused by mutations in the three genes. 56 patients with the GJB2 mutations
      were detected (24.9%), including 30 cases of homozygous mutations (13.3%), 26
      patients (11.6%) of compound heterozygous mutations, and 21 cases (9.33%) of
      single heterozygous mutations. 50 patients with the SLC26A4 mutations were
      detected (22.2%), including 22 cases of homozygous mutations(9.8%), 28 patients
      (12.4%) of compound heterozygous mutations, and 22 cases (9.8%) of single
      heterozygous mutations. mtDNA 12S rRNA A1555G mutation was detected in 5 patients
      (2.2%). mtDNA 12S rRNA 1494C>T mutation was not detected. We verified the results
      by Sanger sequencing. The accuracy of the sequencing results was 100%. The
      SNPscan cost eight hours and 160 yuan (each sample). CONCLUSIONS: Applying
      SNPscan technology can be accurate, rapid and cost-effective diagnostic screening
      in patients with hearing loss for etiology investigation. It is expected to
      become an effective means of large-scale genetic testing for hereditary deafness.

PMID- 27033576
TI  - [Diagnostic value of portable monitor device in patients with potential
      obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To evaluate the diagnostic value of portable monitor device (PMD) in
      potential obstructive sleep apnea hypopnea syndrome (OSAHS) patients. METHODS:
      All patients met the inclusion criteria were asked to finish the questionniar and
      underwent anthropometric measurements, and then completed polysomnography (PSG)
      test and PMD test simultaneously. The correlation between AHI-PMD and AHI-PSG,
      between MinSaO2-PMD and MinSaO2-PSG were analyzed by Spearman analysis. T test
      was used to compare the correlation coefficient between the two groups; ROC
      analysis was used to evaluate the sensitivity and specificity of PMD in diagnosis
      of OSAHS, and got the Cut-off value between moderate and severe OSAHS and mild
      OSAHS. RESULTS: Through PSG test, of all the 111 cases, including 4 simple
      snoring cases, accounting for 3.6%, OSAHS patients with 107 cases, accounting for
      96.4% which including 11 patients (9.9%) with mild, 17 patients (15.3%) with
      moderate, 79 patients (71.2%) with severe. The correlation of AHI-PMD and AHI-PSG
      between moderate and severe OSAHS patients was stronger than simple snoring and
      mild OSAHS patients. The coefficient test between the two groups was
      statistically significant (P=0.026). The correlation of MinSaO2-PMD and MinSaO2
      PSG was statistically significant (P<0.001), the correlation of MinSaO2-PMD and
      MinSaO2-PSG between moderate and severe OSAHS group and snoring and mild OSAHS
      group was not statistically significant (P=0.270). A statistically significant
      correlation between AHI-PMD and AHI-PSG was found (P<0.001). PMD had a
      sensitivity and specificity of 96.9% and 86.7%, respectively (AUC=0.990, 95%CI
      0.970-1.000). The cut-off value between moderate and severe OSAHS and mild OSAHS
      was AHI-PMD>=12 times/h. CONCLUSION: PMD had a satisfactory sensitivity and
      specificity for diagnosing and judging the severity of moderate and severe OSAHS.

PMID- 27033577
TI  - [Analysis of 33 children with deep neck infection].
AB  - OBJECTIVE: To analyze the effective treatment of deep neck infection in children.
      METHODS: Thirty-three cases of deep neck infection treated from September 2005 to
      May 2015 were retrospectively reviewed. To observe the effect of antibiotics and
      surgical drainage. RESULTS: All cases were cured, including one case who was
      complicated with carotid artery rupture and was timely cured by vascular
      interventional therapy, and the cure rate was 100%. CONCLUSION: Combined
      application of broad-spectrum antibiotics and effective surgical drainage are key
      to treat deep neck infection in children. The emergence of repeated small amount
      of bleeding in the nose and throat in children is an indicator for big neck
      vessel rupture and interventional vascular therapy may be considered.

PMID- 27033578
TI  - [Clinical analysis and treatment of 2 examples of recurrent esophageal abscess
      around neck and breast part from operations for extraction of foreign body in
      esophagus].

PMID- 27033579
TI  - [A case of mental cell lymphoma first diagnosed at otorhinolaryngology].

PMID- 27033580
TI  - [Actinomyces infection in post-operation of laryngeal papilloma: one case
      report].

PMID- 27033581
TI  - [Giant nodular goiter presented as a mass in chest wall: a case report].

PMID- 27033582
TI  - [Advances in hereditary hearing loss caused by TMC1 mutations].
AB  - Hearing loss is the most frequent sensorineural disorder worldwild, among which
      about 50% are caused by genetic factors. TMC1 is one of the common genes causing
      hereditary hearing loss. TMC1 mutations can cause pre-lingual profound/severe
      autosomal recessive (DFNB7/11) and post-lingual progressive autosomal dominant
      (DFNA36) non-syndromic hearing loss. Murine models studies show that TMC1, 2 are
      expressed in cochlea inner and outer hair cells and maintain normal
      mechanoelectrical transduction (MET) functions of the hair cells. A growing
      number of evidence indicate that TMC1, 2 are components of the MET complex. It is
      necessary to definite the precise distribution and exact function of TMC1, 2,
      because it is important to understand the regulating mechanism of auditory
      function. 

PMID- 27033583
TI  - [Three applications and the challenge of the big data in otology].
AB  - With the expansion of human practical activities, more and more areas have
      suffered from big data problems. The emergence of big data requires people to
      update the research paradigm and develop new technical methods. This review
      discussed that big data might bring opportunities and challenges in the area of
      auditory implantation, the deafness genome, and auditory pathophysiology, and
      pointed out that we needed to find appropriate theories and methods to make this
      kind of expectation into reality. 

PMID- 27033584
TI  - [Chronic rhinosinusitis with bronchial asthma, what should we concern about?].
AB  - There is a strong association between chronic rhinosinusitis (CRS) and asthma.
      Approximately 10%-50% of CRS patients also have comorbid asthma. These patients
      are more likely to have severe CRS and asthma and higher recurrence rates after
      sinus surgery. Also there may be acute asthma attack during the perioperative
      period. Therefore, we should pay more attention to these patients. Assessment of
      the control level of asthma and pulmonary function should be performed
      preoperatively. And asthma needs to be fully managed in the perioperative period
      to avoid acute asthma attack. Extensive sinus surgery is recommended in these
      patients to reduce the inflammation load. Long-term medical treatment and regular
      follow-up are suggested to achieve well control of CRS and asthma. 

PMID- 27033585
TI  - Discovery, structural characterization and functional analysis of alpha-2
      macroglobulin, a novel immune-related molecule from Holothuria atra.
AB  - The non-specific protease inhibitor alpha-2-macroglobulin (A2M) is a key
      macromolecular glycoprotein that involved in host immune defense against
      pathogens in vertebrates and invertebrates. However, no research regarding A2M
      has been developed in echinoderms to date. In this study, the full-length cDNA of
      A2M was cloned from the sea cucumber (Holothuria atra), which is a tropical
      species widely distributed along the coasts of the South China Sea and designated
      HaA2M. HaA2M possesses all three conserved functional domains of known A2M
      proteins, including the bait region domain, thioester domain and receptor-binding
      domain. Compared to fish and shrimp A2Ms, the histidine residue from the
      catalytical regions is well conserved in HaA2M. HaA2M mRNA was predominantly
      expressed in coelomocytes and, to a lesser extent, in the body wall, intestine
      and respiratory tree. A2M activity was detected in the coelomic fluids of H.
      atra. The mRNA expression and activity levels were investigated in the major
      immune tissues and coelomic fluids of H. atra after challenge with inactivated
      Vibrio alginolyticus or polyriboinosinic polyribocytidylic acid [Poly (I: C)].
      RNA interference (RNAi)-mediated knockdown of HaA2M resulted in a significant
      reduction of HaA2M gene transcript level (86%). RNAi-mediated silencing of HaA2M
      gene significantly decreased the A2M activity (38%) and increased the number of
      viable bacteria (2.8-fold) in the coelomic fluids of H. atra infected by V.
      alginolyticus. Our study, as a whole, supplied the evidences for HaA2M as an
      immune-relevant molecule and it might have multiple functions in the innate
      immune system of H. atra.

PMID- 27033586
TI  - Population Genetic data for 15 Autosomal STR markers in Eastern Turkey.
AB  - The allelic frequency distribution and statistical genetic parameters of forensic
      relevance for 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01,
      D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) in a
      population sample of 802 unrelated individuals in Eastern Turkey. The expected
      performance of these loci for personal identification and paternity testing in
      this population was estimated. Eastern Turkey and other 12 country population
      data were compared using allele frequencies. 

PMID- 27033587
TI  - Transcriptome differences in the rumen of beef steers with variation in feed
      intake and gain.
AB  - BACKGROUND: Feed intake and gain are economically important traits in beef
      production. The rumen wall interacts with feed, microbial populations, and
      fermentation products important to cattle nutrition. As such, it is likely to be
      a critical component in the beef steer's ability to utilize feedstuffs
      efficiently. To identify genes associated with steer feed intake and body weight
      gain traits, and to gain an understanding of molecules and pathways involved in
      feed intake and utilization, RNA sequencing (RNA-Seq) was performed on rumen
      papillae from 16 steers with variation in gain and feed intake. Four steers were
      chosen from each of the four Cartesian quadrants for gain*feed intake and used to
      generate individual RNA-Seq libraries. RESULTS: Normalized read counts from all
      of the mapped reads from each of the four groups of animals were individually
      compared to the other three groups. In addition, differentially expressed genes
      (DEGs) between animals with high and low gain, as well as high and low intake
      were also evaluated. A total of 931 genes were differentially expressed in the
      analyses of the individual groups. Eighty-nine genes were differentially
      expressed between high and low gain animals; and sixty-nine were differentially
      expressed in high versus low intake animals. Several of the genes identified in
      this study have been previously associated with feed efficiency. Among those are
      KLK10, IRX3, COL1A1, CRELD2, HDAC10, IFITM3, and VIM. CONCLUSIONS: Many of the
      genes identified in this study are involved with immune function, inflammation,
      apoptosis, cell growth/proliferation, nutrient transport, and metabolic pathways
      and may be important predictors of feed intake and gain in beef cattle.

PMID- 27033588
TI  - Symmetry-protected ideal Weyl semimetal in HgTe-class materials.
AB  - Ideal Weyl semimetals with all Weyl nodes exactly at the Fermi level and no
      coexisting trivial Fermi surfaces in the bulk, similar to graphene, could feature
      deep physics such as exotic transport phenomena induced by the chiral anomaly.
      Here, we show that HgTe and half-Heusler compounds, under a broad range of in
      plane compressive strain, could be materials in nature realizing ideal Weyl
      semimetals with four pairs of Weyl nodes and topological surface Fermi arcs.
      Generically, we find that the HgTe-class materials with nontrivial band inversion
      and noncentrosymmetry provide a promising arena to realize ideal Weyl semimetals.
      Such ideal Weyl semimetals could further provide a unique platform to study
      emergent phenomena such as the interplay between ideal Weyl fermions and
      superconductivity in the half-Heusler compound LaPtBi. 

PMID- 27033589
TI  - Patients having breast reconstruction should enter into surgery with as much
      information as possible.

PMID- 27033590
TI  - Towards a proposal for a universal diagnostic definition of protein-losing
      enteropathy in Fontan patients: a systematic review.
AB  - OBJECTIVE: A standardised diagnostic definition of protein-losing enteropathy
      (PLE) in Fontan patients serves both patient care and research. The present study
      determined whether a diagnostic definition of PLE was routinely used in published
      clinical Fontan studies, and to identify potentially relevant diagnostic criteria
      for composing a uniform PLE definition. METHODS: A systematic review was
      conducted in adherence to the PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) recommendations. Published clinical Fontan studies
      that were written in English and included at least four patients with PLE were
      selected. PLE definitions were quantitatively analysed using a lateral thinking
      tool in which definitions were fractionated into constituent pieces of
      information (building blocks or diagnostic criteria). RESULTS: We identified 364
      papers. In the final analysis, data from 62 published articles were extracted. A
      diagnostic definition of PLE was used in only 27/62 (43.5%) of selected studies,
      and definitions were very heterogeneous. We identified eight major diagnostic
      criteria. Hypoalbuminaemia (n=23 studies, 85.2%), clinical presentation (n=18,
      66.7%), documentation of enteric protein loss (n=16, 59.3%) and exclusion of
      other causes of hypoproteinaemia (n=17, 63.0%), were the most frequently used
      diagnostic criteria. Most studies used three diagnostic variables (n=13/27,
      48.1%). Cut-off values for laboratory parameters (serum albumin, protein or
      faecal alpha-1-antitrypsin) were frequently incorporated in the PLE definition
      (n=16, 59.3%). CONCLUSIONS: Establishment of a universally accepted PLE
      definition for routine use in clinical research and daily practice is required.
      The diagnostic criteria may help constitute a diagnostic PLE definition.

PMID- 27033591
TI  - Epigenetic conversion of adult dog skin fibroblasts into insulin-secreting cells.
AB  - Diabetes is among the most frequently diagnosed endocrine disorder in dogs and
      its prevalence continues to increase. Medical management of this pathology is
      lifelong and challenging because of the numerous serious complications. A therapy
      based on the use of autologous viable insulin-producing cells to replace the lost
      beta cell mass would be very advantageous. A protocol to enable the epigenetic
      conversion of canine dermal fibroblasts, obtained from a skin biopsy, into
      insulin-producing cells (EpiCC) is described in the present manuscript. Cells
      were briefly exposed to the DNA methyltransferase inhibitor 5-azacytidine (5-aza
      CR) in order to increase their plasticity. This was followed by a three-step
      differentiation protocol that directed the cells towards the pancreatic lineage.
      After 36 days, 38 +/- 6.1% of the treated fibroblasts were converted into EpiCC
      that expressed insulin mRNA and protein. Furthermore, EpiCC were able to release
      insulin into the medium in response to an increased glucose concentration. This
      is the first evidence that generating a renewable autologous, functional source
      of insulin-secreting cells is possible in the dog. This procedure represents a
      novel and promising potential therapy for diabetes in dogs. 

PMID- 27033592
TI  - Field use of N-butylscopolammonium bromide to facilitate thorough ophthalmic
      examination in horses.
AB  - N-butylscopolammonium bromide (NBB), an anticholinergic muscarinic antagonist,
      was assessed as a mydriatic agent for field examination of equine eyes. Six adult
      horses were randomly assigned to four treatments with 2 weeks washout between
      treatments: (1) topical saline/IV saline (negative control); (2) topical
      tropicamide/IV saline (positive control); (3) topical NBB/IV saline; or (4)
      topical saline/IV NBB. Horizontal and vertical pupil diameters, temperature,
      pulse, respiration, pupillary light reflexes (PLRs) and mydriasis sufficient to
      perform complete fundic examination were recorded. Tropicamide induced mydriasis
      in all horses. Topical NBB induced mydriasis in one horse, and IV NBB enabled
      thorough fundic examination in two horses, delayed PLRs without allowing thorough
      examination in two horses and had no effect in two horses. 

PMID- 27033593
TI  - Cytokine expression in peripheral blood mononuclear cells of dogs with mitral
      valve disease.
AB  - Inflammation plays an important role in the pathogenesis of congestive heart
      failure (CHF). In humans with CHF, increased production and high plasma
      concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6,
      IL-1, IL-8 and transforming growth factor-beta (TGF-beta) have been associated
      with disease progression and a negative prognosis. The aim of this study was to
      investigate whether differences in cytokine blood mRNA expression exist between
      clinically healthy dogs and dogs with myxomatous mitral valve disease (MMVD); to
      determine if the expression was related to the severity of MMVD, and to detect
      any correlations with echocardiographic parameters of cardiac remodelling. Twenty
      three dogs with MMVD of varying severity and six clinically healthy dogs were
      included in the study. Whole blood samples were obtained for measurement of mRNA
      expression of IL-1alpha, IL-1beta, IL-6, IL-8, TGF-beta1, TNF-alpha by reverse
      transcriptase-PCR (RT-PCR). There were statistically significant differences
      between clinically healthy dogs and dogs with MMVD for IL-8 and TGF-beta1 gene
      expression. IL-8 expression increased with increasing MMVD severity and TGF-beta1
      expression was higher in asymptomatic dogs with echocardiographic signs of
      cardiac remodelling (American College Veterinary Internal Medicine class B2) than
      in all other groups. These results could suggest the involvement of these
      cytokines at different stages of the disease. 

PMID- 27033594
TI  - Serum insulin concentration in horses: Effect of storage and handling.
AB  - Serum insulin concentration is commonly measured during investigation of
      suspected endocrinopathic disease in horses, but immediate analysis is frequently
      unavailable. The aim of this study was to examine the effect of storing samples
      at room temperature for 72 h as serum and as whole blood, compared to immediate
      separation and freezing. Samples from 14 horses were evaluated. Correlation was
      excellent for all comparisons (>=0.992). Bland-Altman plots revealed a negative
      bias (mean difference 2.16 uIU/mL) in samples stored as whole blood compared to
      serum, but this difference was not considered clinically significant. At two
      commonly used diagnostic cut-offs, there was no effect of storage on result. This
      study indicates that storage at room temperature for 72 h, either as serum or
      whole blood, has minimal effect on measured serum insulin concentration in
      horses. 

PMID- 27033595
TI  - Characteristics and consequences of medical care interruptions in HIV-infected
      patients in France.
AB  - To describe the consequences of medical care interruptions (MCIs) we selected
      patients with at least two medical encounters between January 2006 and June 2013
      in the Dat'AIDS cohort. Patients with any time interval >15 months between two
      visits were defined as having a MCI, as opposed to uninterrupted follow-up (UFU).
      Patients' characteristics at the time of HIV diagnosis and at the censoring date
      were compared between groups. Cox proportional hazards models were built to
      assess the role of interruptions on survival (total and AIDS-free). Of 11 116
      patients, 824 had at least one MCI. These patients were younger at the time of
      HIV diagnosis (30 vs. 33 years, P < 0.0001). MCI was less frequent in men having
      sex with men vs. heterosexual patients [odds ratio (OR) 0.81, 95% confidence
      interval (CI) 0.69-0.96)], and a centre effect was described. MCI was
      independently associated with AIDS (OR 2.54, 95% CI 2.10-3.09) and death (OR
      2.65, 95% CI 1.94-3.61). At the censoring date, 52.2% of patients with at least
      one MCI had viral load below detection vs. 85.3% of the UFU group (P < 0.0001).
      In conclusion, MCIs were associated with patients' survival and with the
      proportion of viral loads below detection in our cohort, compromising individual
      and collective treatment benefits.

PMID- 27033596
TI  - The mood stabilizer valproic acid opposes the effects of dopamine on circadian
      rhythms.
AB  - Endogenous circadian (~24 h) clocks regulate key physiological and cognitive
      processes via rhythmic expression of clock genes. The main circadian pacemaker is
      the hypothalamic suprachiasmatic nucleus (SCN). Mood disorders, including bipolar
      disorder (BD), are commonly associated with disturbed circadian rhythms. Dopamine
      (DA) contributes to mania in BD and has direct impact on clock gene expression.
      Therefore, we hypothesized that high levels of DA during episodes of mania
      contribute to disturbed circadian rhythms in BD. The mood stabilizer valproic
      acid (VPA) also affects circadian rhythms. Thus, we further hypothesized that VPA
      normalizes circadian disturbances caused by elevated levels of DA. To test these
      hypotheses, we examined locomotor rhythms and circadian gene cycling in mice with
      reduced expression of the dopamine transporter (DAT-KD mice), which results in
      elevated DA levels and mania-like behavior. We found that elevated DA signaling
      lengthened the circadian period of behavioral rhythms in DAT-KD mice and clock
      gene expression rhythms in SCN explants. In contrast, we found that VPA shortened
      circadian period of behavioral rhythms in DAT-KD mice and clock gene expression
      rhythms in SCN explants, hippocampal cell lines, and human fibroblasts from BD
      patients. Thus, DA and VPA have opposing effects on circadian period. To test
      whether the impact of VPA on circadian rhythms contributes to its behavioral
      effects, we fed VPA to DAT-deficient Drosophila with and without functioning
      circadian clocks. Consistent with our hypothesis, we found that VPA had potent
      activity-suppressing effects in hyperactive DAT-deficient flies with intact
      circadian clocks. However, these effects were attenuated in DAT-deficient flies
      in which circadian clocks were disrupted, suggesting that VPA functions partly
      through the circadian clock to suppress activity. Here, we provide in vivo and in
      vitro evidence across species that elevated DA signaling lengthens the circadian
      period, an effect remediated by VPA treatment. Hence, VPA may exert beneficial
      effects on mood by normalizing lengthened circadian rhythm period in subjects
      with elevated DA resulting from reduced DAT.

PMID- 27033597
TI  - Aldose reductase mediates retinal microglia activation.
AB  - Retinal microglia (RMG) are one of the major immune cells in charge of
      surveillance of inflammatory responses in the eye. In the absence of an
      inflammatory stimulus, RMG reside predominately in the ganglion layer and inner
      or outer plexiform layers. However, under stress RMG become activated and migrate
      into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in
      cell culture secrete pro-inflammatory cytokines in a manner sensitive to
      downregulation by aldose reductase inhibitors. In this study, we utilized
      CX3CR1(GFP) mice carrying AR mutant alleles to evaluate the role of AR on RMG
      activation and migration in vivo. When tested on an AR(WT) background, IP
      injection of LPS induced RMG activation and migration into the INL and ONL.
      However, this phenomenon was largely prevented by AR inhibitors or in AR null
      mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced
      increases in ocular levels of TNF-alpha and CX3CL-1 in WT mice were substantially
      lower in AR null mice or were reduced by AR inhibitor treatment. These studies
      demonstrate that AR expression in RMG may contribute to the proinflammatory
      phenotypes common to various eye diseases such as uveitis and diabetic
      retinopathy. 

PMID- 27033598
TI  - Salinomycin simultaneously induces apoptosis and autophagy through generation of
      reactive oxygen species in osteosarcoma U2OS cells.
AB  - Salinomycin, a polyether antibiotic, acts as a highly selective potassium
      ionophore. It was reported to anticancer activity on various cancer cell lines.
      In this study, salinomycin was examined on apoptosis and autophagy through
      generation of reactive oxygen species (ROS) in osteosarcoma U2OS cells.
      Apoptosis, autophagy, mitochondrial membrane potential (MMP) and ROS were
      analyzed using flow cytometry. Also, expressions of apoptosis- and autophagy
      related proteins were determined by western blotting. As a result, salinomycin
      triggered apoptosis of U2OS cells, which was accompanied by change of MMP and
      cleavage of caspases-3 and poly (ADP-ribose) polymerase. And salinomycin
      increased the expression of autophagy-related protein and accumulation of acidic
      vesicular organelles (AVO). Salinomycin-induced ROS production promotes both
      apoptosis and autophagy, as evidenced by the result that treatment of N-acetyl-l
      cysteine (NAC), a ROS scavenger, attenuated both apoptosis and autophagy. In
      addition, inhibition of autophagy by 3-methyladenine (3 MA) enhanced the
      salinoymcin-induced apoptosis. Taken together, these results suggested that
      salinomycin-induced autophagy, as a survival mechanism, might be a potential
      strategy through ROS regulation in cancer therapy. 

PMID- 27033599
TI  - Downregulation of HDAC9 inhibits cell proliferation and tumor formation by
      inducing cell cycle arrest in retinoblastoma.
AB  - Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a
      wide variety of normal and abnormal physiological functions. Recently, HDAC9 has
      been found to be overexpressed in some types of human cancers. However, the role
      of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9
      was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in
      prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79
      and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively
      related to cell proliferation in vitro. Further investigation indicated that
      knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in
      retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could
      significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in
      nude mice showed that downregulation of HDAC9 inhibited tumor growth and
      development in vivo. Therefore, our results suggest that HDAC9 could serve as a
      novel potential therapeutic target in the treatment of retinoblastoma. 

PMID- 27033600
TI  - Cafeteria diet-induced obesity causes oxidative damage in white adipose.
AB  - Obesity continues to be one of the most prominent public health dilemmas in the
      world. The complex interaction among the varied causes of obesity makes it a
      particularly challenging problem to address. While typical high-fat purified
      diets successfully induce weight gain in rodents, we have described a more robust
      model of diet-induced obesity based on feeding rats a diet consisting of highly
      palatable, energy-dense human junk foods - the "cafeteria" diet (CAF, 45-53% kcal
      from fat). We previously reported that CAF-fed rats became hyperphagic, gained
      more weight, and developed more severe hyperinsulinemia, hyperglycemia, and
      glucose intolerance compared to the lard-based 45% kcal from fat high fat diet
      fed group. In addition, the CAF diet-fed group displayed a higher degree of
      inflammation in adipose and liver, mitochondrial dysfunction, and an increased
      concentration of lipid-derived, pro-inflammatory mediators. Building upon our
      previous findings, we aimed to determine mechanisms that underlie physiologic
      findings in the CAF diet. We investigated the effect of CAF diet-induced obesity
      on adipose tissue specifically using expression arrays and immunohistochemistry.
      Genomic evidence indicated the CAF diet induced alterations in the white adipose
      gene transcriptome, with notable suppression of glutathione-related genes and
      pathways involved in mitigating oxidative stress. Immunohistochemical analysis
      indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared
      to rats that remained lean on control standard chow diet. Our data indicates that
      the CAF diet drives an increase in oxidative damage in white adipose tissue that
      may affect tissue homeostasis. Oxidative stress drives activation of inflammatory
      kinases that can perturb insulin signaling leading to glucose intolerance and
      diabetes. 

PMID- 27033601
TI  - Mitochondrial DNA triplication and punctual mutations in patients with
      mitochondrial neuromuscular disorders.
AB  - Mitochondrial diseases are a heterogeneous group of disorders caused by the
      impairment of the mitochondrial oxidative phosphorylation system which have been
      associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear
      gene mutations. The clinical phenotypes are very diverse and the spectrum is
      still expanding. As brain and muscle are highly dependent on OXPHOS,
      consequently, neurological disorders and myopathy are common features of mtDNA
      mutations. Mutations in mtDNA can be classified into three categories: large
      scale rearrangements, point mutations in tRNA or rRNA genes and point mutations
      in protein coding genes. In the present report, we screened mitochondrial genes
      of complex I, III, IV and V in 2 patients with mitochondrial neuromuscular
      disorders. The results showed the presence the pathogenic heteroplasmic m.9157G>A
      variation (A211T) in the MT-ATP6 gene in the first patient. We also reported the
      first case of triplication of 9 bp in the mitochondrial NC7 region in Africa and
      Tunisia, in association with the novel m.14924T>C in the MT-CYB gene in the
      second patient with mitochondrial neuromuscular disorder. 

PMID- 27033602
TI  - Cyanine-based 1-amino-1-deoxyglucose as fluorescent probes for glucose
      transporter mediated bioimaging.
AB  - Two novel cyanine-based 1-amino-1-deoxy-beta-glucose conjugates (Glu-1N-Cy3 and
      Glu-1N-Cy5) were designed, synthesized and their fluorescence characteristics
      were studied. Both Glu-1N-Cy3 and Glu-1N-Cy5 accumulate in living HT29 human
      colon cancer cells, which overexpress glucose transporters (GLUTs). The cellular
      uptake of the bioprobes was inhibited by natural GLUT substrate d-glucose and 2
      deoxy-d-glucose. The GLUT specificity of the probes was validated with quercetin,
      which is both a permeant substrate via GLUTs and a high-affinity inhibitor of
      GLUT-mediated glucose transport. Competitive fluorometric assay for GLUT
      substrate cell uptake revealed that Glu-1N-Cy3 and Glu-1N-Cy5 are 5 and 10 times
      more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. This study
      provides fundamental data supporting the potential of these two conjugates as new
      powerful tools for GLUT-mediated theranostics, in vitro and in vivo molecular
      bioimaging and drug R&D.

PMID- 27033603
TI  - Enriched environment housing enhances the sensitivity of mouse pancreatic cancer
      to chemotherapeutic agents.
AB  - Living in an enriched housing environment is an established model of eustress and
      has been consistently shown to reduce the growth of transplanted tumors,
      including pancreatic cancer. Here, we further investigate the influence of an
      enriched environment (EE) on the efficacy of chemotherapy in pancreatic cancer.
      Male C57BL/6 mice were housed in EE or standard environment (SE) conditions and
      transplanted with syngeneic Panc02 pancreatic cancer cells. Tumor-bearing mice
      were treated with 5-fluorouracil (5-FU) or gemcitabine (GEM) to examine their
      sensitivities to chemotherapy. The results showed that both 5-FU and GEM exerted
      the dose dependent inhibition of tumor growth. The tumor inhibition rates of low
      dose 5-FU and GEM were improved from 17.7% and 23.6% to 46.3% and 49.9% by EE
      housing. Importantly, tumor cells isolated from the pancreatic cancer xenografts
      of EE mice had significantly enhanced sensitivities to both 5-FU and GEM (IC50
      for 5-FU: 2.8 MUM versus 27.3 MUM; IC50 for GEM: 0.8 MUM versus 5.0 MUM).
      Furthermore, using microarray analyses, we identified the "ATP-binding cassette
      (ABC) transporter" that was overrepresented among EE-induced down-regulated genes
      in pancreatic cancer. Particularly, the tumoral expression of ABC transporter A8b
      (ABCA8b) was confirmed to be significantly decreased by EE. Over-expression of
      ABCA8b in mouse pancreatic cancer cells led to a marked decrease in the
      sensitivity to chemotherapeutic drugs both in vitro and in vivo. In conclusion,
      our data indicate that benign stressful stimulation can synergistically boost the
      efficiency of chemotherapeutics in pancreatic cancer, which suggests a novel
      strategy for adjuvant cancer therapy. 

PMID- 27033604
TI  - Sphingosine inhibits the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)
      activity.
AB  - The increase in the intracellular Ca(2+) concentration ([Ca(2+)]i) is the key
      variable for many different processes, ranging from regulation of cell
      proliferation to apoptosis. In this work we demonstrated that the sphingolipid
      sphingosine (Sph) increases the [Ca(2+)]i by inhibiting the sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a
      specific inhibitor of this Ca(2+) pump. The results showed that addition of
      sphingosine produced a release of Ca(2+) from the endoplasmic reticulum followed
      by a Ca(2+) entrance from the outside mileu. The results presented in this work
      support that this sphingolipid could control the activity of the SERCA, and hence
      sphingosine may participate in the regulation of [Ca(2+)]I in mammalian cells. 

PMID- 27033605
TI  - Bakuchiol sensitizes cancer cells to TRAIL through ROS- and JNK-mediated
      upregulation of death receptors and downregulation of survival proteins.
AB  - We investigated whether bakuchiol, an analog of resveratrol enhances the
      apoptosis ability of tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL) in cancer cells. Bakuchiol enhanced expression of cell death
      receptor (DR) in TRAIL-sensitive and -resistant colon cancer cells in a dose
      dependent manner. A combination of bakuchiol with TRAIL significantly inhibited
      cell growth of TRAIL sensitive HCT116 and TRAIL resistant HT-29 cells. The
      expression of TRAIL receptors; DR4 and DR5 was significantly increased by
      treatment of bakuchiol, however, the expression of survival proteins (e.g.,
      cFLIP, survivin, XIAP and Bcl2) was suppressed. Moreover, the expression of
      apoptosis related proteins such as cleaved caspase-3, -8, -9 and PARP was
      increased by combination treatment of bakuchiol and TRAIL. Depletion of DR4 or
      DR5 by small interfering RNA significantly reversed the cell growth inhibitory
      effects of bakuchiol in HCT116 and HT-29 cells. Pretreatment with the c-Jun N
      terminal kinase (JNK) inhibitor SP600125 and the reactive oxygen species (ROS)
      scavenger N-acetylcysteine reduced the bakuchiol induced cell growth inhibitory
      effects. The collective results suggest that bakuchiol facilitates TRAIL-induced
      apoptosis in colon cancer cells through up-regulation of the TRAIL receptors; DR4
      and DR5 via ROS/JNK pathway signals. 

PMID- 27033606
TI  - Spontaneous decidualization in pseudopregnant rats with vitamin E deficiency.
AB  - Successful implantation of an embryo requires adequate depth of invasion in the
      endometrium, which depends upon decidualization. The aim of the present study was
      to elucidate why humans experience spontaneous decidualization and menstruation
      while most other mammals do not. We established a spontaneous decidualization
      model in pseudopregnant rats with vitamin E deficiency (VED) to investigate
      mechanisms associated with spontaneous decidualization. Vaginal smears were used
      to monitor bleeding while vitamin E levels were analyzed with a commercial
      vitamin E assay kit. Trypan blue staining was used to observe the implantation
      site at 5.5 days post-coitum (dpc). Uterine morphology, estradiol (E2) and
      progesterone levels, and the anti-oxidation system were evaluated at 5.5, 7.5,
      and 9.5 dpc. The proportion of rats in the VED group exhibiting endometrial
      bleeding gradually increased (5.9%, 32.3%, and 50%) over three consecutive cycles
      of pseudopregnancy. Vitamin E levels in the VED group were markedly lower
      compared to the control group in both the plasma and uterus, while the level of
      vitamin E in the liver did not differ between the control and VED groups.
      Spontaneous decidualization in the VED group was validated by histological
      examination and immunohistochemistry. At 5.5 dpc, the mean serum E2 level in the
      VED group was more than twice that of the control group. The mean total anti
      oxidizing capability, catalase level, and glutathione peroxidase activity were
      significantly reduced in the decidualized portion of the VED group compared to
      controls, while the malondialdehyde level was also significantly higher in the
      decidualized portion of the VED group. We hypothesize that the E2 surge at 5.5
      dpc and increasing levels of reactive oxygen species are responsible for
      spontaneous decidualization in VED rats.

PMID- 27033607
TI  - DDX21 translocates from nucleus to cytoplasm and stimulates the innate immune
      response due to dengue virus infection.
AB  - Successful DENV infection relies on its ability to evade the host innate immune
      system. By using iTRAQ labeling followed by LC-MS/MS analysis, DDX21 was
      identified as a new host RNA helicase involved in the DENV life cycle. In DENV
      infected cells, DDX21 translocates from nucleus to cytoplasm to active the innate
      immune response and thus inhibits DENV replication in the early stages of
      infection. DDX21 is then degraded by the viral NS2B-NS3 protease complex and the
      innate immunity is thus subverted to facilitate DENV replication. The results
      reveal a new mechanism in which DENV subverts the host innate immune system to
      facilitate its replication in host cells. 

PMID- 27033608
TI  - Production in stirred-tank bioreactor of recombinant bovine chymosin B by a high
      level expression transformant clone of Pichia pastoris.
AB  - An intense screening of Pichia pastoris clones transformed with the gene of
      bovine chymosin under methanol-inducible AOX1 promoter was performed, obtaining a
      transformant clone with a higher milk-clotting activity value in comparison with
      our previous studies. The scaling of recombinant-chymosin production was carried
      out by a fed-batch strategy in a stirred-tank bioreactor using biodiesel
      byproduct crude glycerol as the carbon source and pure methanol for the induction
      of chymosin expression, achieving a biomass concentration of 158 g DCW/L and a
      maximum coagulant activity of 192 IMCU/ml after 120 h of methanol induction.
      Recombinant bovine chymosin was purified from bioreactor-fermentation culture by
      a procedure including anion-exchange chromatography which allowed obtaining
      heterologous chymosin with high level of purity and activity; suggesting that
      this downstream step could be scaled up in a successful manner for chymosin
      purification. Thermoestability assay permitted to establish that unformulated
      recombinant chymosin could be stored at 5  degrees C without decrease of enzyme
      activity throughout at least 120 days. Finally, reiterative methanol-inductions
      of recombinant chymosin expression in bioreactor demonstrated that the
      reutilization of cell biomass overcame the low enzyme productivity usually
      reached by P. pastoris system.

PMID- 27033609
TI  - The priority of Antonino D'Antona in describing rhabdomyolysis with acute kidney
      injury, following the Messina earthquake (December 28, 1908). Commentary.
AB  - Following the Messina-Reggio Calabria earthquake (December 28, 1908) outstanding
      medical reports were published by Franz von Colmers (1875-1960), Antonino
      D'Antona (1842-1913), and Rocco Caminiti (1868-1940). The reports of D'Antona and
      Caminiti were heretofore neglected. Colmers, D'Antona and Caminiti described
      crush-syndrome. D'Antona who cured patients in shock also described two deaths
      due to uraemia. This gives him a priority in the description of crush syndrome
      with renal injury which has been traditionally attributed to Bywaters and Beall. 

PMID- 27033610
TI  - Hypochondria, or, the awareness of death that goes against the cure. Commentary.
AB  - Fifteen years after the publication of G. Braddock's paper "Epicureanism, death,
      and the good life" in Philosophical inquiry the time has come to think of what
      actually prevents Epicureanism from taking root in Western societies, thereby
      facilitating our relationship with disease and care: hypochondria. In this
      commentary I analyse the philosophical problem of hypochondria overturning
      Heidegger's idea that awareness of death is positive and calling for medical
      therapies that, through the help of psychology, would act on the causes and
      elimination of hypochondria. 

PMID- 27033611
TI  - Asbestos contamination in feldspar extraction sites: a failure of prevention?
      Commentary.
AB  - Fibrous tremolite is a mineral species belonging to the amphibole group. It is
      present almost everywhere in the world as a natural contaminant of other
      minerals, like talc and vermiculite. It can be also found as a natural
      contaminant of the chrysotile form of asbestos. Tremolite asbestos exposures
      result in respiratory health consequences similar to the other forms of asbestos
      exposure, including lung cancer and mesothelioma. Although abundantly distributed
      on the earth's surface, tremolite is only rarely present in significant deposits
      and it has had little commercial use. Significant presence of amphibole asbestos
      fibers, characterized as tremolite, was identified in mineral powders coming from
      the milling of feldspar rocks extracted from a Sardinian mining site (Italy).
      This evidence raises several problems, in particular the prevention of
      carcinogenic risks for the workers. Feldspar is widespread all over the world and
      every year it is produced in large quantities and it is used for several
      productive processes in many manufacturing industries (over 21 million tons of
      feldspar mined and marketed every year). Until now the presence of tremolite
      asbestos in feldspar has not been described, nor has the possibility of such a
      health hazard for workers involved in mining, milling and handling of rocks from
      feldspar ores been appreciated. Therefore the need for a wider dissemination of
      knowledge of these problems among professionals, in particular mineralogists and
      industrial hygienists, must be emphasized. In fact both disciplines are necessary
      to plan appropriate environmental controls and adequate protections in order to
      achieve safe working conditions. 

PMID- 27033612
TI  - For an alliance between science, ethics and politics in promoting paediatric
      trials. Commentary.
AB  - After several decades during which children tended to be excluded from clinical
      trials, provisions to encourage trials with children have been in place for some
      years both at international level and in individual countries. The Nuffield
      Council on Bioethics has published a broad-ranging report on the subject, which
      makes concrete proposals for decision-makers and comes at a crucial moment in the
      definition of European Union regulations on this topic. 

PMID- 27033613
TI  - Preface, Social aspects and well-being for improving healing processes'
      effectiveness. Preface.

PMID- 27033614
TI  - Social sustainability in healthcare facilities: a rating tool for analysing and
      improving social aspects in environments of care.
AB  - INTRODUCTION: Nowadays several rating systems exist for the evaluation of the
      sustainability of buildings, but often their focus is limited to environmental
      and efficiency aspects. Hospitals are complex constructions in which many
      variables affect hospital processes. Therefore, a research group has developed a
      tool for the evaluation of sustainability in healthcare facilities. METHODOLOGY:
      The paper analyses social sustainability issues through a tool which evaluates
      users' perception from a the quality and well-being perspective. It presents a
      hierarchical structure composed of a criteria and indicators system which is
      organised through a weighing system calculated by using the Analytic Network
      Process. RESULTS AND DISCUSSION: The output is the definition of a tool which
      evaluates how Humanisation, Comfort and Distribution criteria can affect the
      social sustainability of a building. CONCLUSION: Starting from its application,
      it is evident that the instrument enables the improvement of healthcare
      facilities through several design and organisational suggestions for achieving
      healing and sustainable architectures.

PMID- 27033615
TI  - A study of human behavior simulation in architectural design for healthcare
      facilities.
AB  - INTRODUCTION: Current tools and methods in architectural design do not allow
      predicting and evaluating how people will use designed environments before their
      actual realization. OBJECTIVE: To investigate how computational simulation can
      help in evaluating design proposals as far as their use by people is concerned.
      METHODS: Simulation of a medicine distribution procedure in a general hospital
      facility, while accounting for serendipitous social interactions made possible by
      the presence of different users in the same space, at the same time. DISCUSSION:
      The simulation shows how use patterns are influenced by the social and physical
      context in which actors are situated, and demonstrates the significance of the
      proposed method of evaluating hospital designs before construction. The system
      allows simulating use patterns with different degrees of complexity, and enables
      architects to ask new types of questions related to the interactions between
      people and physical settings.

PMID- 27033616
TI  - Health facilities humanisation: design guidelines supported by statistical
      evidence.
AB  - BACKGROUND: Healthcare building humanisation is currently a widely debated issue
      and the development of patient centered and evidence based design is growing
      worldwide. Many international health organizations and researchers understand the
      importance of Patient Centred Design and leading architects incorporate it into
      the design process. In Italy this design approach is still at an early stage. The
      article refers to research commissioned by the Italian Health Ministry and
      carried out by R. Del Nord (Universita degli Studi di Firenze) and G. Peretti
      (Politecnico di Torino) with their collaborators. The scope of the research was
      the definition of design guidelines for healthcare facilities humanisation.
      METHOD: The methodology framework adopted is the well established need and
      performance approach in architectural design. The article deals with the results
      of statistical investigations for the definition and ranking of users' needs and
      the consistent expression of their requirements. The investigations were carried
      out with the cooperation of psychologists of the Universita degli Studi di Torino
      and researchers of the Universita degli Studi di Cagliari. The proposed
      evaluation system allows ranking of health facilities according to the level of
      humanisation achieved. RESULTS: The statistical investigation evidence collected
      allowed the definition of humanisation design guidelines for health-care
      facilities and for the assessment of their specific level of humanisation.

PMID- 27033617
TI  - Humanisation and soft qualities in emergency rooms.
AB  - Scenario. Currently, there are few evaluation methods that analyse social aspects
      in healthcare issues, especially humanisation and well-being, as perceived by
      users in emergency departments which are places in which patients' psycho
      physical well-being is decisive. For this reason, research was conducted to
      create a tool to improve the quality of these areas. METHODOLOGY: In order to
      conduct the research, the work was structured in three phases: the first, based
      on the analysis of State-of-the-Art and the current studies on the interactions
      established between the physical and emotional conditions of the structure and
      the users; the second, through the definition of a questionnaire which explores
      humanisation and comfort aspects; the third, through the application of the
      instrument. RESULTS: The paper presents and analyses data collected from the
      application on a case study in Milan, analysing the responses and proposing
      design suggestions for increasing the quality of emergency environments.
      CONCLUSIONS: In anticipation of future works, the application of such a tool can
      provide the opportunity to improve and enhance quality and staff efficiency in
      emergency department spaces.

PMID- 27033618
TI  - Architectures for paediatric palliative care: how to improve quality of life and
      environmental well-being.
AB  - INTRODUCTION: The influence of the environment on wellness, not only for patients
      themselves but for all care-givers as well, refers to the humanisation principles
      of spaces of care. Commencing with an analysis of existing paediatric hospices,
      the paper examines design suggestions for prosthetic environments, considered as
      a fundamental component in the healing process. METHODOLOGY: A prosthetic
      environment can be created only through a specific knowledge of the real needs of
      users. Therefore, some scholars have conducted research work for defining the
      best practices for healing environments, supported by an assessment and
      comparison of case studies. The methodology is based on two phases: the first is
      based on interviews with experts in hospice design and management and the second,
      through the application of a questionnaire to several users. Discussion and
      Results. The output of the work is the achievement of a logical, sequential and
      participatory broad-spectrum process in the design of health facilities in order
      to cause a sustainable awareness in paediatric hospices. CONCLUSION: Starting
      from the research work, it is necessary to define a scientific method for
      implementing knowledge on health, psychological, perceptual and behavioural needs
      to contribute towards proper planning for meeting the real requirements of users.

PMID- 27033619
TI  - Water use and water saving in Italian hospitals. A preliminary investigation.
AB  - AIM: The aim of this work is to investigate about water use, wastage, saving and
      reuse in hospitals. METHODS: An anonymous ad hoc questionnaire was tested in a
      sample of 36 public hospitals of Lombardy Region (21% of total public hospitals).
      Daily water consumption reported is on average equal to 481 m3, ranging from 30
      to 2280 m3. There is a strong correlation between water consumption and number of
      hospital beds (p < 0.005). In 33 hospitals (92%) water consumption is measured
      and, among them, in about 48% more than one flow meter is installed; 86% consider
      "important" the reduction of water consumption and about 55% recognize that
      wastewater could be minimized within the structures. DISCUSSION: There is
      consensus about the need to train health personnel and to implement technical
      measures to improve the water resources management, but initiatives to raise
      knowledge and awareness of health personnel have been promoted only in 10% of
      hospitals. RESULTS: Results show not only a lack of awareness regarding water use
      and saving among the personnel in general, but also among heads of the hospitas'
      technical office and energy managers as well. For this reason, it will be of
      interest to carry out this investigation at national level and also to develop
      recommendations to support and promote a safe reuse of water in all the
      hospitals.

PMID- 27033620
TI  - Open building and flexibility in healthcare: strategies for shaping spaces for
      social aspects.
AB  - INTRODUCTION: The fast development of technology and medicine influences the
      functioning of healthcare facilities as health promoter for the society, making
      the flexibility a fundamental requirement. Among the many ways to ensure
      adaptability, one that allows change without increasing the building's overall
      size is the Open Building approach. METHODOLOGY: Starting from the analysis of
      the State-of-the-Art and many case-studies, eight parameters of evaluation were
      defined, appraising their relative importance through a weighting system defined
      with several experts. The resulting evaluation tool establishes in what measure
      healthcare facilities follow the Open Building principles. RESULTS AND
      DISCUSSION: The tool is tested to ten case-studies, chosen for their flexible
      features, in order to determine his effectiveness and to identify projects'
      weaknesses and strengths. CONCLUSIONS: The results suggest that many Open
      Building's principles are already in use but, only through a good design
      thinking, it will be possible to guarantee architectures for health adaptable for
      future social challenges.

PMID- 27033621
TI  - The implementation of a Community Health Centre-based primary care model in
      Italy. The experience of the Case della Salute in the Emilia-Romagna Region.
AB  - BACKGROUND: The Comunity Health Centre (CHC) primary care model is a team-based
      health care delivery model intended to provide comprehensive and continuous
      medical care to patients within a defined community. The CHC, Case della Salute
      in Italian, model was introduced in the Emilia-Romagna Region in 2010. METHODS:
      We present updated data on the implementation on the CHC Case della Salute
      primary care model in the Emilia-Romagna Region. RESULTS: There are 67 operating
      CHCs in Emilia-Romagna (update March 2015); 26 small (39%), 24 medium (36%) and
      17 large (25%). Since 2011 the number of operating CHCs has increased by 60%,
      reaching 55% of the target planned CHCs (n. = 122). There is, on average, one
      running CHC per 66.524 inhabitants. 16% of total general practitioners (GPs) and
      8.4% of total family paediatricians working in Emilia-Romagna have their practice
      in CHCs. CHCs offer primary and specialist integrated care, prevention services,
      health education and social care. DISCUSSION: Although preliminary results
      suggest CHCs have fostered primary care's quality and efficiency, more research
      is needed to assess their impact on improving clinical, social and economic
      outcomes.

PMID- 27033622
TI  - Addressing decisions about new hospitals' siting: a multidimensional evaluation
      approach.
AB  - BACKGROUND: Site selection for urban facilities is a crucial topic in planning
      decision processes for the several side effects they produce and the multiple
      criteria involved, especially for healthcare facilities. Nevertheless, the
      location problem has been ignored by most of the existing evaluation systems.
      METHODS: Starting from a deep literature review and the analysis of hospitals in
      10 European cities, the paper proposes an evaluation system divided into four
      macro-areas (Functional quality, Location quality, Environmental quality,
      Economical aspects), each in turn composed by criteria and sub-criteria. RESULTS:
      The evaluation system has been applied for the site selection of "La Citta della
      Salute" in Milan, Italy. Furthermore, the ShOS (Selection hospitals' Site)
      Evaluation Tool has been defined, with the aim of assessing the land suitability
      for new healthcare structures. CONCLUSION: The ShOS evaluation tool improves the
      transparency and robustness of the decision-making process and it could be
      broadly applied.

PMID- 27033623
TI  - Healthcare for all in emerging countries: a preliminary investigation of
      facilities in Kolkata, India.
AB  - INTRODUCTION: India is one of the five countries with the lowest public health
      spending levels: the private medical services are one of the most developed
      fields, meanwhile public health ones are totally inadequate with the most number
      of health facilities concentrated in cities, where only the 25% of the population
      lives. Public facilities are mainly made up of primary level and not well
      distributed on the territories, so they do not guarantee accessibility to a wide
      sample of population, who live in rural areas of India. METHODOLOGY: Starting
      from the analysis of three different health care levels in the Indian context,
      the research team developed a meta-project that considers all the current
      criticisms and the Indian customs through a flexible layout that responds to the
      healthcare needs of population. RESULT AND DISCUSSION: The research work is aimed
      to develop a meta-project that considers all the current criticisms and the
      Indian customs through flexible layouts that responds to the healthcare needs of
      population. CONCLUSION: The innovation of the research work is to develop the
      hygienic aspects, the layout and the distribution, the sub-division of the
      medical functions through the Indian culture and the needs of the country. The
      choice of lowly technologies permits to promote the usage of local materials,
      their maintenance and skills for creating a virtuous economic system.

PMID- 27033624
TI  - Risk factors for dysmenorrhea among young adult female university students.
AB  - OBJECTIVES: The aim of this study was to investigate associated risk factors for
      dysmenorrhea in a sample of Serbian university students. METHODS: A case-control
      study was conducted among undergraduate students (n = 288) attending lectures
      during 2014/2015 academic year at the Faculty of Medical Sciences, University of
      Kragujevac. RESULTS: The only significant associations were between dysmenorrhea
      and age at menarche (OR adjusted = 0.74; 95% CI 0.58-0.95; p = 0.017), family
      history of dysmenorrhea (OR adjusted = 3.39; 95% CI 1.74-6.63; p = 0.000),
      duration of menstrual flow (OR adjusted = 1.52; 95% CI 1.16-1.99; p = 0.002) and
      smoking at least one cigarette a day (OR adjusted = 5.09; 95% CI 1.83-14.15; p =
      0.002). The factors associated with dysmenorrhea were not interacting with each
      other. CONCLUSION: Our results suggest that earlier age at menarche, longer
      duration of menstrual flow, prior family history of dysmenorrhea and smoking at
      least one cigarette a day are important risk factors associated with
      dysmenorrhea. Smoking cessation should be strongly encouraged.

PMID- 27033626
TI  - Health services and health literacy: from the rationale to the many facets of a
      fundamental concept. A literature review.
AB  - BACKGROUND: The aim of this study is to make a critical analysis of the different
      definitions of health literacy to provide a framework of the concept. METHODS: A
      literature search was conducted in PubMed, Embase, PsycINFO, ERIC, Health
      Evidence, Centre for Reviews and Dissemination and Cochrane Library. Google and
      OpenGrey were searched to find additional papers and unpublished works. RESULTS:
      Among 7000 papers founded, we selected 26 works. During the 1990s, authors began
      to systematically study the relationship between health literacy and health
      status, according to a public health view. In the first decade of the new
      century, a new fundamental definition established three progressive degrees of
      health literacy: functional, interactive and critical health literacy. Sorensen
      (in 2012) provided a framework for the development of new assessment tools and
      interventions. CONCLUSION: The improvement of health literacy is a powerful tool
      for the development of a new type of relationship between individuals and the
      health system.

PMID- 27033625
TI  - Emerging trends in consuming behaviours for non-controlled substances by Italian
      urban youth: a cross sectional study.
AB  - INTRODUCTION: We investigated emerging trends in consuming behaviours for non
      controlled substances in a cross sectional study on urban Italian adolescents and
      young adults, the reasons for consumption and risk perception as function of age,
      the relation with lifestyles and finally risk factors associated. METHODS: The
      survey methodology involved the administration of an anonymous questionnaire. It
      consisted of 68 questions, divided into five sections: personal details,
      socioeconomic characteristics, family and peer group, free time and lifestyles,
      and substances use. RESULTS: A total of 2621 adolescents and young adults (14-35
      years old) from seven different Italian cities answered the questionnaire. The
      substances examined were mainly used recreationally (alcohol, energy drinks and
      smart-drugs) or to improve physical and sexual performance (physical performance
      enhancing drugs, anabolic steroids and male sexual enhancement). The knowledge of
      the health related harm arising from the use of these products was very high for
      alcohol (> 90%), high for smart-drugs (> 70%), but significantly lower for
      anabolic steroids, drugs for sexual enhancement (~ 60%), physical performance
      enhancing drugs or energy drinks (~ 55%). The principal risks factors for
      consumption were: the influence of friends (OR: 8.8), attending recreational
      places (OR: 5.4) aged between 25-35 years (OR: 3.0), be male (OR: 2.5) and having
      a bad relationship with the mother (OR: 2.1). CONCLUSIONS: These results have
      implication for prevention and early intervention programs of "physically and
      psychologically enhancing" non controlled substances use, which similarly to what
      is frequently advised for classical illicit drugs should focus on information
      campaigns and awareness initiatives especially addressed to young male adults who
      go clubbing, live outside the family and showed closed links with peers.

PMID- 27033627
TI  - The right to food, food donation and microbiological problems of food safety: an
      experience in the territory of Florence.
AB  - AIM: The aim of this study is to understand whether the freezing without a rapid
      blast chiller represents a storage method for food at the end of shelf life that
      guarantees microbiological food safety, so to be considered an effective tool for
      the appropriate management of food in charitable organizations. METHODS: The
      study has been performed on 90 food samples, among those that a charitable
      foodservice trust receives by the large-scale distribution. The products have
      been frozen using a domestic refrigerator. The indicators used were: total
      aerobic microbial count, Escherichia coli, Salmonella spp, Staphylococcus aureus,
      Campylobacter spp, sulphite reducing clostridia. RESULTS: The results show that
      the preservation of the chosen fresh products at the end of shelf life in
      refrigerators, frozen without the use of chillers, is a potential management
      strategy to avoid the loss of edible food, while maintaining the safety
      standards.

PMID- 27033628
TI  - Technology-based intervention for healthy lifestyle promotion in Italian
      adolescents.
AB  - INTRODUCTION: Healthy lifestyle promotion programs are essential to prevent
      metabolic diseases such as obesity and diabetes. Adolescents could represent the
      ideal target population especially using serious web games. OBJECTIVE: To test
      the improvement of knowledge about healthy nutrition in adolescents and to
      analyze participants' enjoyment in playing the web game "Gustavo in Gnam's
      Planet" in comparison with a leisure web game. SUBJECTS AND METHODS: Sixty-five
      adolescents were engaged in three supervised group sessions. Measures about
      healthy food knowledge and games' enjoyment were collected during the three
      stages of assessment. RESULTS: After playing Gustavo in Gnam's Planet,
      participants significantly improved their knowledge on a healthy diet, compared
      to the recreational web games; whereas the level of fun experienced while playing
      the recreational and the educational games was not significantly different.
      CONCLUSIONS: Gustavo in Gnam's Planet is an important promising tool, with
      entertainment property, to promote a healthy lifestyle in Italian adolescents.

PMID- 27033629
TI  - Health risks related to illegal and on-line sale of drugs and food supplements:
      results of a survey on marketed products in Italy from 2011 to 2013.
AB  - OBJECTIVES: The increasing illegal and on-line market of medicines and food
      supplements is helping the widespread diffusion of harmful counterfeit and
      forbidden products among consumers of developed countries. The objectives of this
      survey were the description of the main frauds recognized by public officers and
      the detection of illegal or counterfeit drugs and food supplements. METHODS:
      Medicines and food supplements found by Police forces on the illegal market or
      resulting from seizures made by Italian Customs authorities were visually
      inspected and analysed to evaluate their quality and the presence of other
      undeclared substances. RESULTS: The visual inspection and the chemical analysis
      revealed unsuitable packaging (mostly lacking of adequate information for
      consumers), absence of the declared active substances and presence of undeclared
      active substances. Products containing doping agents, illegal substances and
      active ingredients requiring medical supervision were found. CONCLUSION: The
      present work confirmed the health risk associated with assumption of medicines
      purchased on the Internet and from the illegal supply chain and evidenced a new
      threat to consumer safety related to the presence of pharmaceutical active
      ingredients in food supplements claiming to contain only "natural ingredients".

PMID- 27033630
TI  - Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti
      viral Therapy.
AB  - Cyclophilin A (CypA) is a key member of immunophilins that has peptidyl-prolyl
      cis/trans isomerase (PPIase) activity. Besides acting as a cellular receptor for
      immunosuppressive drug cyclosporine A (CsA), CypA is involved in various cellular
      activities. CypA has an important role in viral infection which either
      facilitates or inhibits their replication. Inhibition of CypA via inhibitors is
      useful for overcoming several viral infections, indicating that CypA is an
      attractive target for anti-viral therapy. Collectively, these facts demonstrate
      the critical roles of CypA in mediating or inhibiting viral infections,
      suggesting that CypA can be an attractive cellular target for the development of
      anti-viral therapy.

PMID- 27033631
TI  - Emerging trends in epidemiology and management of infections caused by carbapenem
      resistant Enterobacteriaceae.
AB  - The recent emergence and spread of infections caused by carbapenem-resistant
      Enterobacteriaceae (CRE) are concerning because carbapenems have represented a
      last line of defense against resistant strains of gram-negative pathogens.
      Existing therapies against CRE include tigecycline, the recently approved drug
      ceftazidime-avibactam, and older drugs not widely used in recent years, such as
      colistin, fosfomycin, and aminoglycosides. Best practices for use of the
      available drugs are not well defined. New therapeutic options with activity
      against CRE offer the opportunity to enhance our current approach to managing
      patients with infections due to CRE. The purpose of this report is to review the
      evolving epidemiology and treatment of infections due to CRE. As part of the
      treatment overview, this manuscript will discuss supportive data for antibiotics
      currently being used in the treatment of infections due to CRE, as well as those
      recently approved and in late-stage development. 

PMID- 27033632
TI  - BlaB-15, a new BlaB metallo-beta-lactamase variant found in an Elizabethkingia
      miricola clinical isolate.
AB  - A multidrug-resistant strain of Elizabethkingia miricola was isolated from the
      urine of a 2-year-old boy hospitalized for severe clinical conditions. The strain
      produces 2 metallo-beta-lactamases belonging to subclasses B1 and B3: a new BlaB
      variant (BlaB-15) and a GOB-7-like enzyme. 

PMID- 27033633
TI  - Nafamostat mesilate improves function recovery after stroke by inhibiting
      neuroinflammation in rats.
AB  - Inflammation plays an important role in stroke pathology, making it a promising
      target for stroke intervention. Nafamostat mesilate (NM), a wide-spectrum serine
      protease inhibitor, is commonly used for treating inflammatory diseases, such as
      pancreatitis. However, its effect on neuroinflammation after stroke was unknown.
      Hence, the effects of NM on the inflammatory response post stroke were
      characterized. After transient middle cerebral artery occlusion (tMCAO) in rats,
      NM reduced the infarct size, improved behavioral functions, decreased the
      expression of proinflammatory mediators (TNF-alpha, IL-1beta, iNOS and COX-2) in
      a time-dependent manner and promoted the expression of different anti
      inflammatory factors (CD206, TGF-beta, IL-10 and IL-4) at different time points.
      Furthermore, NM could inhibit the expression of proinflammatory mediators and
      promote anti-inflammatory mediators expression in rat primary microglia following
      exposure to thrombin combined with oxygen-glucose deprivation (OGD). The immune
      modulatory effect of NM might be partly due to its inhibition of the NF-kappaB
      signaling pathway and inflammasome activation after tMCAO. In addition, NM
      significantly inhibited the infiltration of macrophage, neutrophil and T
      lymphocytes, which was partly mediated by the inhibition of monocyte chemotactic
      protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1). Taken together, our results indicated that NM can
      provide long-term protection of the brain against tMCAO by modulating a broad
      components of the inflammatory response. 

PMID- 27033634
TI  - Seasonal Trivalent Influenza Vaccination During Pregnancy and the Incidence of
      Stillbirth: Population-Based Retrospective Cohort Study.
AB  - BACKGROUND: Although antenatal influenza vaccination is an important public
      health intervention for preventing serious infection in pregnant women and
      newborns, reported vaccine coverage is often <50%. Concern for the safety to the
      fetus is a commonly cited reason for vaccine hesitancy and refusal. The incidence
      of stillbirth following pandemic vaccination has been previously studied;
      however, no population-based study has evaluated the incidence of stillbirth
      following seasonal trivalent influenza vaccination. METHODS: We used
      probabilistic linking of perinatal and maternal vaccination records to establish
      a cohort of 58 008 births occurring between April 2012 and December 2013.
      Stillbirth was defined as birth >=20 weeks' gestation with an Apgar score of zero
      at 1 and 5 minutes following delivery. Cox regression models adjusted for
      maternal smoking, Indigenous status, and propensity for vaccination were used to
      calculate adjusted hazard ratios (aHRs) in vaccinated and unvaccinated mothers.
      RESULTS: A total of 5076 (8.8%) pregnant women received trivalent influenza
      vaccine and 377 stillbirths occurred. There were 5.0 and 3.0 stillbirths per 100
      000 pregnancy-days among unvaccinated and vaccinated women, respectively. After
      adjustment, stillbirth was 51% less likely among vaccinated vs unvaccinated
      mothers (aHR, 0.49; 95% confidence interval [CI], .29-.84). The largest relative
      reduction in stillbirths was observed for births occurring just after influenza
      season (aHR, 0.33; 95% CI, .12-.88). CONCLUSIONS: Mothers who received seasonal
      TIV during pregnancy were significantly less likely to experience stillbirth
      compared with unvaccinated mothers. These results support the safety of seasonal
      influenza immunization during pregnancy and suggest a protective effect.

PMID- 27033635
TI  - Ambient air pollution, weather changes, and outpatient visits for allergic
      conjunctivitis: A retrospective registry study.
AB  - Allergic conjunctivitis is a common problem that significantly impairs patients'
      quality of life. Whether air pollution serves as a risk factor for the
      development of allergic conjunctivitis remains elusive. In this paper, we assess
      the relationship between air pollutants and weather conditions with outpatient
      visits for allergic conjunctivitis. By using a time-series analysis based on the
      largest dataset ever assembled to date, we found that the number of outpatient
      visits for allergic conjunctivitis was significantly correlated with the levels
      of NO2, O3, and temperature, while its association with humidity was
      statistically marginal. No associations between PM10, PM2.5, SO2, or wind
      velocity and outpatient visits were seen. Subgroup analyses showed that sex
      seemed to modify the effects of humidity on outpatient visits for allergic
      conjunctivitis, but not for NO2, O3, or temperature. People younger than 40 were
      found to be susceptible to changes of all four parameters, while those older than
      40 were only consistently affected by NO2 levels. Our findings revealed that
      higher levels of ambient NO2, O3, and temperature increase the chances of
      outpatient visits for allergic conjunctivitis. Ambient air pollution and weather
      changes may contribute to the worsening of allergic conjunctivitis. 

PMID- 27033636
TI  - Coexpression network analysis of the genes regulated by two types of resistance
      responses to powdery mildew in wheat.
AB  - Powdery mildew disease caused by Blumeria graminis f. sp. tritici (Bgt) inflicts
      severe economic losses in wheat crops. A systematic understanding of the
      molecular mechanisms involved in wheat resistance to Bgt is essential for
      effectively controlling the disease. Here, using the diploid wheat Triticum
      urartu as a host, the genes regulated by immune (IM) and hypersensitive reaction
      (HR) resistance responses to Bgt were investigated through transcriptome
      sequencing. Four gene coexpression networks (GCNs) were developed using
      transcriptomic data generated for 20 T. urartu accessions showing IM, HR or
      susceptible responses. The powdery mildew resistance regulated (PMRR) genes whose
      expression was significantly correlated with Bgt resistance were identified, and
      they tended to be hubs and enriched in six major modules. A wide occurrence of
      negative regulation of PMRR genes was observed. Three new candidate immune
      receptor genes (TRIUR3_13045, TRIUR3_01037 and TRIUR3_06195) positively
      associated with Bgt resistance were discovered. Finally, the involvement of
      TRIUR3_01037 in Bgt resistance was tentatively verified through cosegregation
      analysis in a F2 population and functional expression assay in Bgt susceptible
      leaf cells. This research provides insights into the global network properties of
      PMRR genes. Potential molecular differences between IM and HR resistance
      responses to Bgt are discussed. 

PMID- 27033637
TI  - Prognostic significance of fever-induced Brugada syndrome.
AB  - BACKGROUND: In Brugada syndrome (BrS), spontaneous type 1 electrocardiogram (ECG)
      is an established risk marker for fatal arrhythmias whereas drug-induced type 1
      ECG shows a relatively benign prognosis. No study has analyzed the prognosis of
      fever-induced type 1 ECG (F-type1) in a large BrS cohort. OBJECTIVES: The
      objectives of this study were to assess the prognosis of F-type1 in asymptomatic
      BrS and to compare the effects of fever and drugs on ECG parameters. METHODS: One
      hundred twelve patients with BrS who developed F-type1 were retrospectively
      enrolled. Prognosis was evaluated in 88 asymptomatic patients. In a subgroup (n =
      52), ECG parameters of multiple ECGs (at baseline, during fever, and after drug
      challenge) were analyzed. RESULTS: Eighty-eight asymptomatic patients had a mean
      age of 45.8 +/- 18.7 years, and 71.6% (67 of 88) were men. Twenty-one percent (18
      of 88) had a family history of sudden cardiac death, and 26.4% (14 of 53) carried
      a pathogenic SCN5A mutation. Drug challenge was positive in 29 of 36 patients
      tested (80.6%). The risk of ventricular fibrillation in asymptomatic patients was
      0.9%/y (3 of 88; 43.6 +/- 37.4 months). ST-segment elevation in lead V2 during
      fever and after drug challenge was not significantly different (0.41 +/- 0.21 ms
      during fever and 0.40 +/- 0.30 ms after drug challenge; P > .05). Fever shortened
      the PR interval compared to baseline, whereas drug challenge resulted in
      prolonged PR interval and QRS duration (PR interval: 169 +/- 29 ms at baseline,
      148 +/- 45 ms during fever, and 202 +/- 35 ms after drug challenge; QRS duration:
      97 +/- 18 ms at baseline, 92 +/- 28 ms during fever, and 117 +/- 21 ms after drug
      challenge). CONCLUSION: Patients with BrS who develop F-type1 are at risk of
      arrhythmic events. F-type1 appears to develop through a more complex mechanism as
      compared with drug-induced type 1 ECG.

PMID- 27033638
TI  - Design and synthesis of antimicrobial, anticoagulant, and anticholinesterase
      hybrid molecules from 4-methylumbelliferone.
AB  - We designed and synthesized new series of diverse triazoles, isoxazoles,
      isoxazolines, and aziridines linked 4-methylumbelliferone 1 using intermolecular
      1,3-dipolar cycloaddition reactions. Structures of these compounds were
      established on the basis of (1)H NMR, (13)C NMR, and ESI-HRMS. All prepared
      compounds were evaluated for their antimicrobial, anticoagulant, and
      anticholinesterase activities. Interestingly, among the tested molecules, some of
      the analogs displayed better activities than the parent 4-methylumbelliferone 1
      such as 6a and 6d for their antifungal properties. Moreover, compounds 4, 5, 6,
      and 7 showed the importance of the added fragments to 4-methylumbelliferone 1 via
      the linker methylene to have good activity. 

PMID- 27033639
TI  - Noncovalent Functionalization of Graphene and Graphene Oxide for Energy
      Materials, Biosensing, Catalytic, and Biomedical Applications.
AB  - This Review focuses on noncovalent functionalization of graphene and graphene
      oxide with various species involving biomolecules, polymers, drugs, metals and
      metal oxide-based nanoparticles, quantum dots, magnetic nanostructures, other
      carbon allotropes (fullerenes, nanodiamonds, and carbon nanotubes), and graphene
      analogues (MoS2, WS2). A brief description of pi-pi interactions, van der Waals
      forces, ionic interactions, and hydrogen bonding allowing noncovalent
      modification of graphene and graphene oxide is first given. The main part of this
      Review is devoted to tailored functionalization for applications in drug
      delivery, energy materials, solar cells, water splitting, biosensing, bioimaging,
      environmental, catalytic, photocatalytic, and biomedical technologies. A
      significant part of this Review explores the possibilities of graphene/graphene
      oxide-based 3D superstructures and their use in lithium-ion batteries. This
      Review ends with a look at challenges and future prospects of noncovalently
      modified graphene and graphene oxide.

PMID- 27033640
TI  - HABITAT DIFFERENCES IN THE TIMING OF REPRODUCTION OF THE INVASIVE ALGA SARGASSUM
      MUTICUM (PHAEOPHYTA, SARGASSACEAE) OVER TIDAL AND LUNAR CYCLES(1).
AB  - Sargassum muticum (Yendo) Fensholt is an invasive species that is firmly
      established on intertidal and subtidal rocky shores of Europe and the Pacific
      coast of North America. Local success and spread of S. muticum is thought to rely
      on its reproductive potential that seems dependent on exogenous factors like
      tidal and lunar cycles. This study is the first to compare the reproductive
      patterns (periodicity of egg expulsion and embryo settlement) of this invader in
      two different habitats: the middle and low intertidal. The combination of
      monthly, daily, and tidal samples at triplicate sites within each habitat showed
      a semilunar periodicity of egg expulsion and embryo settlement coincident with
      increasing tidal amplitude just before full and new moons. In both habitats,
      duration of each egg expulsion event was ~1 week, and embryo settlement occurred
      during the first daily low tide and with the incoming high tide during spring
      tides. However, both expulsion and settlement started 1-2 d earlier, expulsion
      saturation was faster, and settlement was higher in the mid- compared to the low
      intertidal. Our results suggest that the exact timing of gamete expulsion and
      embryo release of S. muticum responds to local factors, including tidal cues,
      which result in differences between mid- and low-intertidal habitats. 

PMID- 27033641
TI  - EFFECT OF CARBONIC ANHYDRASE INHIBITORS ON THE INORGANIC CARBON UPTAKE BY
      PHYTOPLANKTON NATURAL ASSEMBLAGES(1).
AB  - The role of carbonic anhydrase (CA) in inorganic carbon acquisition (dissolved
      inorganic carbon, DIC) was examined in Alboran Sea phytoplankton assemblages. The
      study area was characterized by a relatively high variability in nutrient
      concentration and in abundance and taxonomic composition of phytoplankton.
      Therefore, the relationship between environmental variability and capacity for
      using HCO3 (-) via external CA (eCA) was examined. Acetazolamide (AZ, an
      inhibitor of eCA) inhibited the primary productivity (PP) in 50% of the samples,
      with inhibition percentages ranging from 13% to 60%. The AZ effect was more
      prominent in the samples that exhibited PP >1 mg C . m(-3)  . h(-1) , indicating
      that the contribution of eCA to the DIC photosynthetic flux was irrelevant at low
      PP. The inhibition of primary productivity by AZ was significantly correlated to
      the abundance of diatoms. However, there was no a relationship between AZ effect
      and CO2 partial pressure (pCO2 ) or nutrient concentration, indicating that the
      variability in the PP percentage supported by eCA was mainly due to differences
      in taxonomic composition of the phytoplankton assemblages. Ethoxyzolamide (EZ, an
      inhibitor of both external and internal CA) affected 13 of 14 analyzed samples,
      with PP inhibition percentages varying from 50% to 95%. The effects of AZ and EZ
      were partially reversed by doubling DIC concentration. These results imply that
      CA activity (external and/or internal) was involved in inorganic carbon
      acquisition in most the samples. However, EZ effect was not correlated with pCO2
      or taxonomic composition of the phytoplankton. 

PMID- 27033642
TI  - GROWTH AND PHOTOPROTECTION IN THREE DINOFLAGELLATES (INCLUDING TWO STRAINS OF
      ALEXANDRIUM TAMARENSE) AND ONE DIATOM EXPOSED TO FOUR WEEKS OF NATURAL AND
      ENHANCED ULTRAVIOLET-B RADIATION(1).
AB  - Long-term growth response to natural solar radiation with enhanced ultraviolet-B
      (UVB) exposure was examined in two species of dinoflagellates [Alexandrium
      tamarense (M. Lebour) Balech, At, and Heterocapsa triquetra (Ehrenb.) F. Stein,
      Ht], including two strains of A. tamarense, one from Spain and another from UK,
      and one diatom species (Thalassiosira pseudonana Hasle et Heimdal). We examined
      whether variable photoprotection (mycosporine-like amino acids [MAAs] and
      xanthophyll-cycle pigments) affected photosynthetic performance, phytoplankton
      light absorption, and growth. Growth rate was significantly reduced under
      enhanced UVB for the UK strain of At and for Ht (both grew very little) as well
      as for the diatom (that maintained high growth rates), but there was no effect
      for the Spanish strain of At. MAA concentration was high in the dinoflagellates,
      but undetectable in the diatom, which instead used the xanthophyll cycle for
      photoprotection. The highest cell concentrations of MAAs and photoprotective
      pigments were observed in the UK strain of At, along with lowest growth rates and
      Fv /Fm , indicating high stress levels. In contrast, the Spanish strain showed
      progressive acclimation to the experimental conditions, with no significant
      difference in growth between treatments. Increase in total MAAs followed linearly
      the cumulative UVB of the preceding day, and both total and primary MAAs were
      maintained at higher constitutive levels in this strain. Acclimation to enhanced
      UVB in the diatom resulted in an increase in PSII activity and reduction in
      nonphotochemical quenching, indicating an increased resistance to photoinhibition
      after a few weeks. All four species showed increased phytoplankton light
      absorption under enhanced UVB. Large intrastrain differences suggest a need to
      consider more closely intraspecific variability in UV studies. 

PMID- 27033643
TI  - ECTOCELLULAR GLUCOSIDASE AND PEPTIDASE ACTIVITY OF THE MIXOTROPHIC DINOFLAGELLATE
      PROROCENTRUM MINIMUM (DINOPHYCEAE)(1).
AB  - The activities of the enzymes alpha- and beta-glucosidase, and leucine
      aminopeptidase were measured in cultures of the dinoflagellate Prorocentrum
      minimum (Pavill.) J. Schiller and in field samples collected during
      dinoflagellate blooms occurring in tributaries of the Chesapeake Bay, Maryland,
      USA. Activities were measured using fluorogenic artificial substrates and
      partitioned among the >5 MUm size fraction, small microbes fraction (0.1-5 MUm),
      and dissolved phase (<0.1 MUm). P. minimum and most other photosynthetic
      dinoflagellates are >5 MUm in size and thus can be separated from the small
      microbes fraction, which contains most bacteria. Little to no glucosidase
      activity was detected associated with the >5 MUm size fraction in cultures or in
      field samples, with most of the activity (67% to 93% in cultures, 54% to 100% in
      field samples) in the small microbes size fraction for both alpha and beta
      glucosidase. In contrast, 67% to 90% of the total leucine aminopeptidase (LAP)
      activity in cultures was measured in the >5 MUm fraction. Within a culture, LAP
      activity in the size fraction containing P. minimum decreased in response to
      ammonium and urea additions, but not in response to nitrate. In field samples,
      LAP activity was positively correlated with dinoflagellate abundance and chl a,
      and negatively correlated with ammonium concentration. During blooms, up to 34%
      of LAP activity was associated with the >5 MUm fraction, indicating that when
      abundant, dinoflagellates may make a substantial contribution to ectocellular LAP
      activity in the water column. 

PMID- 27033644
TI  - SEASONAL VARIABILITY IN POLYUNSATURATED ALDEHYDE PRODUCTION POTENTIAL AMONG
      STRAINS OF SKELETONEMA MARINOI (BACILLARIOPHYCEAE)(1).
AB  - The cosmopolitan bloom-forming diatom Skeletonema marinoi Sarno et Zingone is
      known to produce toxic polyunsaturated aldehydes (PUAs) in response to cell
      damage that can affect a diverse suite of organisms, including grazing species
      and competitor plankton species. The production of PUAs in nine different S.
      marinoi strains isolated at three different times of the year (spring, summer,
      and autumn) was assessed in relation to the predominant conditions at the time of
      isolation from Gullmar Fjord, Skagerrak. During the initial stages of growth, PUA
      production potential of S. marinoi was generally the highest in summer strains,
      although there was a substantial variation among strains isolated at the same
      time. Spring strains, however, showed a strong capacity for increased PUA
      production potential in later stage cultures with diminishing nutrient levels,
      reaching amounts similar to those observed in summer strains. In contrast, PUA
      production potentials of summer and autumn strains did not change significantly
      from the original values. There is negligible grazing pressure during the spring
      bloom in Gullmar Fjord, but a potential for high competition for resources, such
      as nutrients, toward the later stages of the bloom. In contrast, grazing pressure
      is much greater during summer and autumn, and there may also be nutrient
      limitation at this time. The PUA production potentials of S. marinoi appear to
      reflect the ecological conditions at the time of isolation with higher production
      potentials in strains isolated when conditions were likely to be less beneficial
      for survival. 

PMID- 27033645
TI  - COASTAL DIATOM-ENVIRONMENT RELATIONSHIPS IN THE BRACKISH BALTIC SEA(1).
AB  - High-quality calibration data sets are required when diatom assemblages are used
      for monitoring ecological change or reconstructing palaeo-environments. The
      quality of such data sets can be validated, in addition to other criteria, by the
      percentage of significant unimodal species responses as a measure of the length
      of an environmental gradient. This study presents diatom-environment
      relationships analyzed from a robust data set of diatom communities living on
      submerged stones along a 2,000 km long coastline in the Baltic Sea area,
      including 524 samples taken at 135 sites and covering a salinity gradient from
      0.4 to 11.4. Altogether, 487 diatom taxa belonging to 102 genera were recorded.
      Detrended canonical correspondence analysis showed that salinity was the
      overriding environmental factor regulating diatom community composition, while
      exposure to wave action and nutrient concentrations were of secondary importance.
      Modeling the abundances of the 58 most common diatom taxa yielded significant
      relationships with salinity for 57 taxa. Twenty-three taxa showing monotonic
      responses were species with optimum distributions in freshwater or marine waters.
      Thirty-four taxa showing unimodal responses were brackish-water species with
      maximum distributions at different salinities. Separate analyses for small (cell
      biovolume <1,000 MUm(3) ) and large (>=1,000 MUm(3) ) taxa yielded similar
      results. In previous studies along shorter salinity gradients, large and small
      epilithic diatom taxa responded differently. From our large data, we conclude
      that counts of large diatom taxa alone seem sufficient for indicating salinity
      changes in coastal environments with high precision. 

PMID- 27033646
TI  - SEASONAL CHANGES IN SIZE STRUCTURE OF SARGASSUM AND TURBINARIA POPULATIONS
      (PHAEOPHYCEAE) ON TROPICAL REEF FLATS IN THE SOUTHERN RED SEA(1).
AB  - Seasonal variation in density, thallus length and biomass, population size
      structure, and allometric length-biomass relationships was investigated in
      populations of Sargassum ilicifolium (Turner) C. Agardh, Sargassum subrepandum
      (Forssk.) C. Agardh, and Turbinaria triquetra (J. Agardh) Kutz. (Phaeophyceae) on
      shallow reef flats in the southern Red Sea. Thallus length and biomass varied
      strongly with season, with the highest values occurring in the cooler months.
      Thallus densities showed no significant temporal variation. Log-total biomass
      versus log-density relationships were positive throughout the growth season
      without any decrease in the slope of the relationship. In two populations,
      biomass-density combinations approached the interspecific biomass-density line,
      but the massive annual shedding of modules occurred before self-thinning would
      set in. Allometric length-biomass relationships varied with season in all
      populations and were associated with seasonal module initiation, growth, and
      shedding. Evidence of a strong asymmetric competition was found in two high
      density populations. These populations showed a predominance of small thalli
      during peak development, asymmetrical Lorenz curves, increasing Gini
      coefficients, and increasing thallus length relative to biomass during the main
      growth phase. In two other less crowded populations, small thalli were absent
      during peak development, Lorenz curves were symmetrical, and Gini coefficients
      decreased during the main growth phase. In these populations, size equalization
      appears to be due to responses at the modular level rather than size-dependent
      mortality. We conclude that changes in size structure in this highly seasonal
      environment are determined by module dynamics, modified by asymmetric competition
      in some populations, with a minor role of recruitment and no regulatory effect of
      self-thinning. 

PMID- 27033647
TI  - PHENOTYPIC PLASTICITY INDUCED IN TRANSPLANT EXPERIMENTS IN A MUTUALISTIC
      ASSOCIATION BETWEEN THE RED ALGA JANIA ADHAERENS (RHODOPHYTA, CORALLINALES) AND
      THE SPONGE HALICLONA CAERULEA (PORIFERA: HAPLOSCLERIDA): MORPHOLOGICAL RESPONSES
      OF THE ALGA(1).
AB  - The association between the red macroalga Jania adhaerens J. V. Lamour. and the
      sponge Haliclona caerulea is the most successful life-form between 2 and 4 m
      depth in Mazatlan Bay (Mexican Pacific). J. adhaerens colonizes the rocky
      intertidal area and penetrates into deeper areas only when it lives in
      association with H. caerulea. The aposymbiotic form of the sponge has not been
      reported in the bay. To understand the ecological success of this association, we
      examined the capacity of J. adhaerens to acclimate in Mazatlan Bay using
      transplant experiments. The transplanted aposymbiotic J. adhaerens did not
      survive the first 2 weeks; however, J. adhaerens when living in association with
      H. caerulea, acclimated easily to depth, showing no sign of mortality during the
      103 d of the experiment. We conclude that the ability of J. adhaerens to colonize
      in deeper areas in this hydrodynamic environment may in part rely on the
      protection provided by the sponge to the algal canopy. Both species contribute to
      the shape of the associated form. Nevertheless, the morphological variation in
      the association appears to be dominated by the variation in J. adhaerens canopy
      to regulate pigment self-shading under light-limited conditions and/or tissue
      resistance under high hydrodynamics. Consequently, our results are consistent
      with light as the abiotic controlling factor, which regulates the lower depth
      distribution of the association in Mazatlan Bay, through limiting the growth rate
      of J. adhaerens. Hydrodynamics may determine the upper limit of the association
      by imposing high mass losses. 

PMID- 27033648
TI  - PHYSIOLOGICAL RESPONSES OF ECKLONIA RADIATA (LAMINARIALES) TO A LATITUDINAL
      GRADIENT IN OCEAN TEMPERATURE(1).
AB  - We tested the ability of sporophytes of a small kelp, Ecklonia radiata (C.
      Agardh) J. Agardh, to adjust their photosynthesis, respiration, and cellular
      processes to increasingly warm ocean climates along a latitudinal gradient in
      ocean temperature (~4 degrees C). Tissue concentrations of pigment and nutrients
      decreased with increasing ocean temperature. Concurrently, a number of gradual
      changes in the metabolic balance of E. radiata took place along the latitudinal
      gradient. Warm-acclimatized kelps had 50% lower photosynthetic rates and 90%
      lower respiration rates at the optimum temperature than did cool-acclimatized
      kelps. A reduction in temperature sensitivity was also observed as a reduction in
      Q10 -values from cool- to warm-acclimatized kelps for gross photosynthesis (Q10 :
      3.35 to 1.45) and respiration (Q10 : 3.82 to 1.65). Respiration rates were more
      sensitive to increasing experimental temperatures (10% higher Q10 -values) than
      photosynthesis and had a higher optimum temperature, irrespective of sampling
      location. To maintain a positive carbon balance, E. radiata increased the
      critical light demand (Ec ) exponentially with increasing experimental
      temperature. The temperature dependency of Ec was, however, weakened with
      increasing ocean temperature, such that the critical light demand was relaxed in
      kelp acclimated to higher ocean temperatures. Nevertheless, calculations of
      critical depth limits suggested that direct effects of future temperature
      increases are unlikely to be as strong as effects of reduced water clarity,
      another globally increasing problem in coastal areas. 

PMID- 27033649
TI  - HOMOTHALLIC AUXOSPORULATION IN PSEUDO-NITZSCHIA BRASILIANA (BACILLARIOPHYTA)(1).
AB  - Most pennate diatoms are allogamous, and various types of mating systems have
      been described. In Pseudo-nitzschia, reproductive stages have been identified in
      some species, and it is generally accepted that the genus is mainly
      heterothallic. Here we report homothallic auxosporulation of Pseudo-nitzschia
      brasiliana Lundholm, Hasle et G. A. Fryxell. To our knowledge, this is the first
      verified description of homothallic sexual reproduction in the genus. Auxospore
      formation was observed in all 16 subclones derived from three initial clonal
      cultures of P. brasiliana. Pairing was followed by production of two gametes per
      gametangium, which fused to give two zygotes. Each zygote (early auxospore) was
      initially spherical and adhered to one girdle band of the parental frustule. The
      two auxospores tended to expand parallel to each other and perpendicular to the
      parental frustule. Elongation was synchronous, slightly asynchronous, or totally
      asynchronous. The entire process of sexual reproduction, from gamete formation to
      the appearance of the initial vegetative cells, took 2-4 d. The occurrence of sex
      in a homothallic species seems an advantageous life strategy for this species in
      that any encounter between cells of the right size class is potentially sexual. 

PMID- 27033650
TI  - HIGH-THROUGHPUT SCREENING TECHNOLOGY FOR MONITORING PHYTOHORMONE PRODUCTION IN
      MICROALGAE(1).
AB  - New miniaturized techniques for multiplying microalgae and estimating their
      phytohormone production were developed; in these methods, the strains to be
      tested are cultivated in microtitre plates, and the phytohormones in suspensions
      of the cultures are measured by direct ELISAs. Specific and sensitive ELISAs for
      determining abscisic acid (ABA), indole-3-acetic acid (IAA), cis- and trans
      zeatin riboside, isopentenyladenosine (iPR), and other less common cytokinins
      were developed for this purpose. Polyclonal antibodies used in the ABA and IAA
      assays were raised against C1- and C1'- conjugates of the compounds with BSA,
      respectively, and thus were specific for the free acids and their respective C1
      derivatives. The use of cytokinin ribosides coupled via their sugar residues to
      BSA as haptens generally led to antibodies that bound free bases, 9-glycosides
      and nucleotides, but with high specificity for the corresponding N(6) -side
      chains. Using internal standards, dilution assays, and authentic [(2) H] and [(3)
      H] recovery markers, it was shown that the ELISAs could be used to estimate
      contents of the selected phytohormones in the cultures. The ELISAs provided
      reliable and very fast estimates of the selected phytohormones, at concentrations
      ranging from 0.01 to 10 pmol . mL(-1) in various microalgal strains. In addition,
      a recently developed HPLC selected ion monitoring mass spectrometry (HPLC-SIM-MS)
      method was used to calibrate and validate the ELISA results and confirm the
      presence of the detected phytohormones in immunoaffinity-purified extracts. Where
      independent validation of results is deemed necessary, the use of quantitative
      HPLC-MS is recommended for each new microalgal strain to be tested. 

PMID- 27033651
TI  - RESPONSES TO SOLAR UV RADIATION OF THE DIATOM SKELETONEMA COSTATUM
      (BACILLARIOPHYCEAE) GROWN AT DIFFERENT Zn(2+) CONCENTRATIONS(1).
AB  - Zn availability in the ocean has been suggested to limit primary production by
      affecting CO2 acquisition processes for photosynthesis, therefore influencing the
      global carbon cycle. Also, UV radiation (UVR, 280-400 nm) is known to affect
      primary production in different ways. It remains to be ascertained whether Zn
      availability and UVR can act synergistically, antagonistically, or independently
      on oceanic primary production. We cultured the cosmopolitan diatom Skeletonema
      costatum (Grev.) Cleve under different radiation treatments with or without UVR
      (only photosynthetically active radiation), at 0, 3, and 10 pmol . L(-1) Zn(2+) .
      Specific growth rate, photosynthetic carbon assimilation, external carbonic
      anhydrase (eCA) activity, and estimated cell abundance increased with increasing
      concentrations of Zn(2+) from 0 to 3 and 10 pmol . L(-1) , irrespective of the
      radiation treatment. Higher eCA activity was observed in the cells grown at the
      high level of Zn(2+) in the presence of UVR. An approximately linear relationship
      between MU and the daily dose of PAR was observed at 3 and 10 pmol . L(-1) Zn(2+)
      concentrations. However, the dependency of MU on the daily PAR dose disappeared
      when the cells were grown in the presence of UVR, which overall depressed both MU
      and photosynthetic carbon assimilation. The inhibitory effect of UVR was
      inversely related to Zn(2+) concentrations. The ultraviolet-B (UVB)-related
      inhibition of growth and photosynthesis decreased with time, reflecting a faster
      acclimation of the cells to UVR at replete Zn(2+) levels. Overall, growth in the
      presence of higher Zn(2+) concentrations reduced the sensitivity to UV radiation
      in Skeletonema costatum. 

PMID- 27033652
TI  - NOVEL ICE-BINDING PROTEINS FROM A PSYCHROPHILIC ANTARCTIC ALGA
      (CHLAMYDOMONADACEAE, CHLOROPHYCEAE)(1).
AB  - Many cold-adapted unicellular plants express ice-active proteins, but at present,
      only one type of such proteins has been described, and it shows no resemblance to
      higher plant antifreezes. Here, we describe four isoforms of a second and very
      active type of extracellular ice-binding protein (IBP) from a unicellular
      chlamydomonad alga collected from an Antarctic intertidal location. The alga is a
      euryhaline psychrophile that, based on sequences of the alpha tubulin gene and an
      IBP gene, appears to be the same as a snow alga collected on Petrel Island,
      Antarctica. The IBPs, which do not resemble any known antifreezes, have strong
      recrystallization inhibition activity and have an ability to slow the drainage of
      brine from sea ice. These properties, by maintaining liquid environments, may
      increase survival of the cells in freezing environments. The IBPs have a
      repeating TXT motif, which has previously been implicated in ice binding in
      insect antifreezes and a ryegrass antifreeze. 

PMID- 27033653
TI  - STRAIN VARIATION IN KARLODINIUM VENEFICUM (DINOPHYCEAE): TOXIN PROFILES,
      PIGMENTS, AND GROWTH CHARACTERISTICS(1).
AB  - Karlodinium veneficum (D. Ballant.) J. Larsen strains, 16 from the U.S. Atlantic
      eastern seaboard and two from New Zealand (CAWD66 and CAWD83), were used to
      characterize toxin profiles during batch culture. All 18 strains were determined
      as the same species based on ITS sequence analyses, a positive signal in a
      chloroplast real-time PCR assay and pigment composition. Five karlotoxin 1 (KmTx
      1) containing strains were analyzed from the Chesapeake Bay, and 10 karlotoxin 2
      (KmTx 2) strains were analyzed from Florida to North Carolina. One strain (MD5)
      from the Chesapeake Bay produced no detectable toxin. The two cultures from New
      Zealand contained both novel karlotoxins with lower masses and earlier elution
      times. Toxin type did not change during batch culture, although the KmTx
      phenotype did change in some strains under extensive (months) phototrophic growth
      in replete media. KmTx cell quota did not change during batch culture for most
      strains. The mass spectrum for every KmTx examined showed a pattern of multiple
      coeluting congeners within each HPLC peak, with masses typically differing by 16
      amu. KmTx congeners tested showed nearly a 500-fold range in specific hemolytic
      activity, with KmTx 1 (typically occurring at lower cellular levels) most
      hemolytic and CAWD66 toxin least hemolytic, while KmTx 2 and the CAWD83 toxin had
      similar intermediate specific activity. Despite morphological, genetic, and
      photopigment indicators consistent with species homogeneity among the 18 strains
      of K. veneficum, the high degree of toxin variability suggests different
      functional roles among strains that likely coexist in situ. 

PMID- 27033654
TI  - LIPID CLASS, CAROTENOID, AND TOXIN DYNAMICS OF KARENIA BREVIS (DINOPHYCEAE)
      DURING DIEL VERTICAL MIGRATION(1).
AB  - The internal lipid, carotenoid, and toxin concentrations of Karenia brevis (C. C.
      Davis) Gert Hansen and Moestrup are influenced by its ability to use ambient
      light and nutrients for growth and reproduction. This study investigated changes
      in K. brevis toxicity, lipid class, and carotenoid concentrations in low-light,
      nitrate-replete (250 MUmol quanta . m(-2)  . s(-1) , 80 MUM NO3 ); high-light,
      nitrate-replete (960 MUmol quanta . m(-2)  . s(-1) , 80 MUM NO3 ); and high
      light, nitrate-reduced (960 MUmol quanta . m(-2)  . s(-1) , <5 MUM NO3 )
      mesocosms. Reverse-phase HPLC quantified the epoxidation state (EPS) of the
      xanthophyll-cycle pigments diadinoxanthin and diatoxanthin, and a Chromarod
      Iatroscan thin layer chromatography/flame ionization detection (TLC/FID) system
      quantified changes in lipid class concentrations. EPS did not exceed 0.20 in the
      low-light mesocosm, but increased to 0.65 in the high-light mesocosms.
      Triacylglycerol and monogalactosyldiacylglycerol (MGDG) were the largest lipid
      classes consisting of 9.3% to 48.7% and 37.3% to 69.7% of total lipid,
      respectively. Both lipid classes also experienced the greatest concentration
      changes in high-light experiments. K. brevis increased EPS and toxin
      concentrations while decreasing its lipid concentrations under high light. K.
      brevis may mobilize its toxins into the surrounding environment by reducing lipid
      concentrations, such as sterols, limiting competition, or toxins are released
      because lipids are decreased in high light, reducing any protective mechanism
      against their own toxins. 

PMID- 27033655
TI  - SURVEY FOR KARLOTOXIN PRODUCTION IN 15 SPECIES OF GYMNODINIOID DINOFLAGELLATES
      (KARENIACEAE, DINOPHYTA)(1).
AB  - Toxin analysis of 15 species of Kareniaceae revealed the presence of karlotoxin,
      KmTx 2, in only a single species (Karlodinium veneficum) but with variable
      activity in strains from the Swan (Km(Swan) Tx 2-1, 2.1 pg . cell(-1) ; and
      Km(Swan) Tx 2-2, 0.53 pg . cell(-1) ), Huon (Km(Huon) Tx 2, 0.86 pg . cell(-1) ),
      and Derwent rivers (<0.001 pg . cell(-1) ) in Australia. A newly isolated
      Southern Ocean species, Karlodinium conicum, contained a novel poorly hemolytic
      karlotoxin analogue (Kmconicum Tx, 2.8 pg . cell(-1) ). The hemolytic potency
      (HD50%) of the Australian karlotoxins were as follows: Km(Swan) Tx 2-1 (65.9 +/-
      4.8 ng) and Km(Swan) Tx 2-2 (63.4 +/- 3.7 ng), Km(Huon) Tx 2 (343 +/- 4.9 ng),
      and Kmconicum Tx (>4,000 ng). Species from the closely related genera Takayama
      (T. helix, T. tasmanica, T. tuberculata), Karenia (K. asterichroma, K. brevis, K.
      mikimotoi, K. papilionacea, K. umbella), and Karlodinium (Ka. australe, Ka.
      antarcticum, Ka. ballantinum, Ka. corrugatum, Ka. decipiens) were all
      consistently negative for karlotoxin production. Brevetoxin (PbTx) was only
      detected in K. brevis, and hemolytic activity was only observed in Ka. veneficum
      strains. 

PMID- 27033656
TI  - ENVIRONMENTAL MODULATION OF KARLOTOXIN LEVELS IN STRAINS OF THE COSMOPOLITAN
      DINOFLAGELLATE, KARLODINIUM VENEFICUM (DINOPHYCEAE)(1).
AB  - We examined the influence of N or P depletion, alternate N- or P-sources,
      salinity, and temperature on karlotoxin (KmTx) production in strains of
      Karlodinium veneficum (D. Ballant.) J. Larsen, an ichthyotoxic dinoflagellate
      that shows a high degree of variability of toxicity in situ. The six strains
      examined represented KmTx 1 (CCMP 1974, MD 2) and KmTx 2 (CCMP 2064, CCMP 2283,
      MBM1) producers, and one strain that did not produce detectable karlotoxin under
      nutrient-replete growth conditions (MD 5). We hypothesized that growth-limiting
      conditions would result in higher cell quotas of karlotoxin. KmTx was present in
      toxic strains during all growth phases and increased in stationary and senescent
      phase cultures under low N or P, generally 2- to 5-fold but with some
      observations in the 10- to 15-fold range. No karlotoxin was observed under low-N
      or low-P conditions in the nontoxic strain MD 5. Nutrient-quality (NO3 , NH4 ,
      urea, and glycerophosphate) did not affect growth rate, but growth on NH4
      produced 2- to 3-fold higher cellular toxicity and a 50% higher ratio of KmTx 1
      1:KmTx 1-3 in CCMP 1974. CCMP 1974 showed higher cellular toxicity at low
      salinity (<=5 ppt) and high temperature (25 degrees C). Our results suggested
      that given the presence of a toxic strain of K. veneficum in situ, the existence
      of environmental conditions that favor cellular accumulation of karlotoxin is
      likely a significant factor underlying K. veneficum-related fish kills that
      require both high cell densities (10(4)  . mL(-1) ) and high cellular toxin
      quotas relative to those generally observed in nutrient-replete cultures. 

PMID- 27033657
TI  - A VANADIUM BROMOPEROXIDASE CATALYZES THE FORMATION OF HIGH-MOLECULAR-WEIGHT
      COMPLEXES BETWEEN BROWN ALGAL PHENOLIC SUBSTANCES AND ALGINATES(1).
AB  - The interaction between phenolic substances (PS) and alginates (ALG) has been
      suggested to play a role in the structure of the cell walls of brown seaweeds.
      However, no clear evidence for this interaction was reported. Vanadium
      bromoperoxidase (VBPO) has been proposed as a possible catalyst for the binding
      of PS to ALG. In this work, we studied the interaction between PS and ALG from
      brown algae using size exclusion chromatography (SEC) and optical tweezers
      microscopy. The analysis by SEC revealed that ALG forms a high-molecular-weight
      complex with PS. To study the formation of this molecular complex, we
      investigated the in vitro interaction of purified ALG from Fucus vesiculosus L.
      with purified PS from Padina gymnospora (Kutz.) Sond., in the presence or absence
      of VBPO. The interaction between PS and ALG only occurred when VBPO was added,
      indicating that the enzyme is essential for the binding process. The interaction
      of these molecules led to a reduction in ALG viscosity. We propose that VBPO
      promotes the binding of PS molecules to the ALG uronic acids residues, and we
      also suggest that PS are components of the brown algal cell walls. 

PMID- 27033658
TI  - A CELLULOSE SYNTHASE (CESA) GENE FROM THE RED ALGA PORPHYRA YEZOENSIS
      (RHODOPHYTA)(1).
AB  - The cell walls of Porphyra species, like those of land plants, contain cellulose
      microfibrils that are synthesized by clusters of cellulose synthase enzymes
      ("terminal complexes"), which move in the plasma membrane. However, the
      morphologies of the Porphyra terminal complexes and the cellulose microfibrils
      they produce differ from those of land plants. To characterize the genetic basis
      for these differences, we have identified, cloned, and sequenced a cellulose
      synthase (CESA) gene from Porphyra yezoensis Ueda strain TU-1. A partial cDNA
      sequence was identified in the P. yezoensis expressed sequence tag (EST) index
      using a land plant CESA sequence as a query. High-efficiency thermal asymmetric
      interlaced PCR was used to amplify sequences upstream of the cDNA sequence from
      P. yezoensis genomic DNA. Using the resulting genomic sequences as queries, we
      identified additional EST sequences and a full-length cDNA clone, which we named
      PyCESA1. The conceptual translation of PyCESA1 includes the four catalytic
      domains and the N- and C-terminal transmembrane domains that characterize CESA
      proteins. Genomic PCR demonstrated that PyCESA1 contains no introns. Southern
      blot analysis indicated that P. yezoensis has at least three genomic sequences
      with high similarity to the cloned gene; two of these are pseudogenes based on
      analysis of amplified genomic sequences. The P. yezoensis CESA peptide sequence
      is most similar to cellulose synthase sequences from the oomycete Phytophthora
      infestans and from cyanobacteria. Comparing the CESA genes of P. yezoensis and
      land plants may facilitate identification of sequences that control terminal
      complex and cellulose microfibril morphology. 

PMID- 27033659
TI  - COCCOLITH FUNCTION AND MORPHOGENESIS: INSIGHTS FROM APPENDAGE-BEARING
      COCCOLITHOPHORES OF THE FAMILY SYRACOSPHAERACEAE (HAPTOPHYTA)(1).
AB  - The morphology of three remarkable genera of coccolithophores, Ophiaster,
      Michaelsarsia, and Calciopappus, is reviewed based on new images using field
      emission scanning electron microscopy. Each of these genera characteristically
      forms coccospheres with long appendages formed of highly modified coccoliths,
      which radiate from either the circum-flagellar pole of the coccosphere
      (Calciopappus and Michaelsarsia) or the antapical pole (Ophiaster). For each
      genus, it is shown that the appendage coccoliths can also occur in an alternative
      orientation appressed to the main coccosphere. It is hypothesized that the
      appendage coccoliths are initially deployed in the appressed orientation and that
      extension of the appendages is a dynamic response to environmental stress. The
      observations suggest that coccoliths are more sophisticatedly adapted to specific
      functions than has been assumed and that the cytoskeleton plays more active roles
      in coccolith morphogenesis and deployment than has previously been inferred. 

PMID- 27033660
TI  - MORPHOLOGICAL AND MOLECULAR CHARACTERIZATION OF SPECIES OF THE GENUS CENTROCERAS
      (CERAMIACEAE, CERAMIALES), INCLUDING TWO NEW SPECIES(1).
AB  - Centroceras clavulatum (C. Agardh) Montagne is widely reported as being a prime
      example of a cosmopolitan red algal species. Instead, C. clavulatum is here
      determined as restricted to northern Chile, Peru, southern California, southern
      Australia, and New Zealand. Specimens identified using the current species
      concept for "C. clavulatum" fall into nine morphological groups that correspond
      to highly supported clades in phylogenetic analyses. Three of these clades
      correspond to the resurrected species Centroceras gasparrinii (Meneghini)
      Kutzing, C. hyalacanthum Kutzing, and C. micracanthum Kutzing. Two others are
      recognized as new species: Centroceras rodmanii sp. nov. from southern Chile,
      which is characterized by hooked spines arranged in a whorl at the node, a spine
      or flattened gland cell cut off from the first cortical initials, and a single
      acropetal cortical cell issued from the second cortical initials; and C.
      tetrachotomum sp. nov. from South Africa, which has a tetrachotomous branching
      pattern, straight spines in a whorl, an acropetal cortical cell and a spine or a
      flattened gland cell cut off from the first cortical initials, and a two-celled
      acropetal filament cut off from the second cortical initials. Three additional
      species from South Africa are also recognized as distinct species. All
      phylogenetic analyses of the rbcL gene, LSU rDNA, and SSU rDNA were consistent
      with the vegetative and tetrasporangial morphological distinctions, thus
      supporting the resurrection of three species and the description of two new
      species. 

PMID- 27033661
TI  - SYMBIODINIUM NATANS SP. NOV.: A "FREE-LIVING" DINOFLAGELLATE FROM TENERIFE
      (NORTHEAST-ATLANTIC OCEAN)(1).
AB  - We examined a free-living Symbiodinium species by light and electron microscopy
      and nuclear-encoded partial LSU rDNA sequence data. The strain was isolated from
      a net plankton sample collected in near-shore waters at Tenerife, the Canary
      Islands. Comparing the thecal plate tabulation of the free-living Symbiodinium to
      that of S. microadriaticum Freud., it became clear that a few but significant
      differences could be noted. The isolate possessed two rather than three antapical
      plates, six rather than seven to eight postcingular plates, and finally four
      rather than five apical plates. The electron microscopic study also revealed the
      presence of an eyespot with brick-shaped contents in the sulcal region and a
      narrow anterior plate with small knob-like structures. Bayesian analysis revealed
      the free-living Symbiodinium to be a member of the earliest diverging clade A.
      However, it did not group within subclade AI (=temperate A) or any other
      subclades within clade A. Rather, it occupied an isolated position, and this was
      also supported by sequence divergence estimates. On the basis of comparative
      analysis of the thecal plate tabulation and the inferred phylogeny, we propose
      that the Symbiodinium isolate from Tenerife is a new species (viz. S. natans). To
      elucidate further the species diversity of Symbiodinium, particularly those
      inhabiting coral reefs, we suggest combining morphological features of the thecal
      plate pattern with gene sequence data. Indeed, future examination of motile
      stages originating from symbiont isolates will demonstrate if this proves a
      feasible way to identify and characterize additional species of Symbiodinium and
      thus match ribotypes or clusters of ribotypes to species. 

PMID- 27033662
TI  - LAURENCIA MARILZAE SP. NOV. (CERAMIALES, RHODOPHYTA) FROM THE CANARY ISLANDS,
      SPAIN, BASED ON MORPHOLOGICAL AND MOLECULAR EVIDENCE(1).
AB  - Laurencia marilzae Gil-Rodriguez, Senties et M.T. Fujii sp. nov. is described
      based on specimens that have been collected from the Canary Islands. This new
      species is characterized by distinctive yellow-orange as its natural habitat
      color, a terete thallus, four pericentral cells per vegetative axial segment,
      presence of secondary pit-connections between adjacent cortical cells, markedly
      projecting cortical cells, and also by the presence of corps en cerise (one per
      cell) present in all cells of the thallus (cortical, medullary, including
      pericentral and axial cells, and trichoblasts). It also has a procarp-bearing
      segment with five pericentral cells and tetrasporangia that are produced from the
      third and fourth pericentral cells, which are arranged in a parallel manner in
      relation to fertile branchlets. The phylogenetic position of this taxon was
      inferred based on chloroplast-encoded rbcL gene sequence analyses. Within the
      Laurencia assemblage, L. marilzae formed a distinctive lineage sister to all
      other Laurencia species analyzed. Previously, a large number of unique diterpenes
      dactylomelane derivatives were isolated and identified from this taxon. L.
      marilzae is morphologically, genetically, and chemically distinct from all other
      related species of the Laurencia complex described. 

PMID- 27033663
TI  - CHUKCHIA PEDICELLATA GEN. ET SP. NOV. AND C. ENDOPHYTICA NOV. COMB., ARCTIC
      ENDEMIC BROWN ALGAE (PHAEOPHYCEAE)(1).
AB  - Study of the north Alaskan brown algal epiphyte Chukchia pedicellata sp. nov.
      suggests an apparently close relationship to Phaeostroma. Phaeostroma
      endophyticum S. Lund from east Greenland, Bylot Island, Nunavut, Canada, shows
      generic identity with Chukchia and specific differences from C. pedicellata.
      Comparison of C. pedicellata and P. pustulosum Kuck. (the type species of
      Phaeostroma) shows morphological, cytological, reproductive, and distributional
      differences. We recognize novelty of C. pedicellata and necessity to broaden the
      species description of P. endophyticum, which becomes Chukchia endophytica. C.
      endophytica is distinguished by its dimorphic vegetative habit, its large
      plurilocular sporangia, and the putative ability of the sporangia to digest host
      tissue to accommodate development within the host. Absence of pyrenoids and novel
      plurilocular sporangia in both species suggests that they are not members of the
      Ectocarpales, sensu lato. 

PMID- 27033664
TI  - BIODIVERSITY OF CORALLINE ALGAE IN THE NORTHEASTERN ATLANTIC INCLUDING CORALLINA
      CAESPITOSA SP. NOV. (CORALLINOIDEAE, RHODOPHYTA)(1).
AB  - The Corallinoideae (Corallinaceae) is represented in the northeastern Atlantic by
      Corallina officinalis L.; Corallina elongata J. Ellis et Sol.; Haliptilon
      squamatum (L.) H. W. Johans., L. M. Irvine et A. M. Webster; and Jania rubens
      (L.) J. V. Lamour. The delimitation of these geniculate coralline red algae is
      based primarily on morphological characters. Molecular analysis based on cox1 and
      18S rRNA gene phylogenies supported the division of the Corallinoideae into the
      tribes Janieae and Corallineae. Within the Janieae, a sequence difference of 46
      48 bp (8.6%-8.9%) between specimens of H. squamatum and J. rubens in the cox1
      phylogeny leads us to conclude that they are congeneric. J. rubens var. rubens
      and J. rubens var. corniculata (L.) Yendo clustered together in both phylogenies,
      suggesting that for those genes, there was no genetic basis for the morphological
      variation. Within the Corallineae, it appears that in some regions, the name C.
      elongata has been misapplied. C. officinalis samples formed two clusters that
      differed by 45-54 bp (8.4%-10.0%), indicating species-level divergence, and
      morphological differences were sufficient to define two species. One of these
      clusters was consistent with the morphology of the type specimen of C.
      officinalis (LINN 1293.9). The other species cluster is therefore described here
      as Corallina caespitosa sp. nov. This study has demonstrated that there is a
      clear need for a revision of the genus Corallina to determine the extent of
      "pseudocryptic" diversity in this group of red algae. 

PMID- 27033665
TI  - USING A NONANALYTICAL APPROACH TO MODEL NONLINEAR DYNAMICS IN PHOTOSYNTHESIS AT
      THE PHOTOSYSTEM LEVEL(1).
AB  - Nonlinear dynamics in photon capture and uptake at the photosystem level may have
      a strong effect on photosynthetic yield. However, the magnitude of such effects
      is difficult to estimate theoretically because nonlinear systems often cannot be
      represented accurately using equations. A nonanalytical simulation was developed
      that used a simple decision tree and Monte Carlo methods, instead of equations,
      to model how a population of photosystems absorbs and utilizes photons from an
      ambient light field. This simulation replicated realistic kinetics in the closure
      and variable fluorescence yield of PSII on the single-turnover timescale, as well
      as the saturating behavior in light-driven electron flow that is observed in
      nature with increasing irradiance. This simulation indicated that the transfer of
      absorbed photon energy among PSII units can introduce strong nonlinear
      enhancement in light-driven electron flow. However, this effect was seen only in
      populations with particular photosynthetic states as determined by physiological
      properties of PSII. Other populations with the same degree of energy transfer but
      with different photosynthetic states exhibited little enhancement in electron
      flow and, in some cases, a reduction. This nonanalytical approach provides a
      simple means to quantify theoretically how nonlinear dynamics in photosynthesis
      arise at the photosystem level and how these dynamics may act to enhance or
      constrain photosynthetic rates and yields. Such simulations can provide
      quantitative insight into different physiological bases of nonlinear light
      harvesting dynamics and identify those that would have the strongest theoretical
      influence and thus warrant closer experimental examination. 

PMID- 27033666
TI  - Meta-analysis of association between Helicobacter pylori infection and multiple
      sclerosis.
AB  - Despite recent research focus on the association between Helicobacter pylori (H.
      pylori) infection and multiple sclerosis (MS) there is no consensus about the
      findings. To obtain a more comprehensive estimate of the association we conducted
      a meta-analysis to determine the prevalence of H. pylori infection in MS patients
      and healthy controls. Pubmed and EMBASE were searched to identify eligible
      studies. Nine studies were selected for inclusion, involving 2806 cases (1553
      patients with MS and 1253 controls). Overall, the prevalence of H. pylori
      infection in MS patients was lower than that in control groups (24.66% vs.
      31.84%, OR=0.69, 95% CI: 0.57-0.83, P<0.0001). Subgroup analysis revealed that
      the levels of H.pylori infection among MS patients were lower than for control
      subjects in Western countries (11.90% vs. 16.08%, OR=0.63, 95% CI: 0.43-0.91,
      P=0.01), but were not statistically significant in Eastern countries (39.39% vs.
      43.82%, OR=0.79, 95% CI: 0.55-1.14, P=0.20). Our data show that H. pylori
      infection and MS is negatively correlated, especially in Western countries.
      Whether H. pylori infection is a protective factor against MS risk should thus be
      addressed in large-scale and prospective studies.

PMID- 27033667
TI  - Interplay of orientation selectivity and the power of low- and high-gamma bands
      in the cat primary visual cortex.
AB  - Gamma oscillations are ubiquitous in brain and are believed to be inevitable for
      information processing in brain. Here, we report that distinct bands (low, 30
      40Hz and high gamma, 60-80Hz) of stimulus-triggered gamma oscillations are
      systematically linked to the orientation selectivity index (OSI) of neurons in
      the cat primary visual cortex. The gamma-power is high for the highly selective
      neurons in the low-gamma band, whereas it is high for the broadly selective
      neurons in the high-gamma band. We suggest that the low-gamma band is principally
      implicated in feed-forward excitatory flow, whereas the high-gamma band governs
      the flow of this excitation.

PMID- 27033668
TI  - A GABBR2 gene variant modifies pathophysiology in Huntington's disease.
AB  - Striatal degeneration in Huntington's disease (HD) causes changes in cortico
      subcortical pathways. Transcranial magnetic stimulation (TMS) is a valuable tool
      for assessing pathophysiology within these pathways, yet has had limited
      application in HD. As cortico-subcortical pathways are largely mediated by GABA
      and dopamine receptor genes, understanding how these genes modulate
      neurophysiology in HD may provide new insights into how underlying pathology maps
      onto clinical phenotype. Twenty-nine participants with HD underwent motor cortex
      stimulation, while corticospinal excitability, cortical inhibition and
      intracortical facilitation were indexed via peripheral electromyography. Single
      nucleotide polymorphism mapping was performed across six genes that are known to
      modulate cortico-subcortical pathways (GABRA2, GABBR1, GABBR2, DRD1, DRD2, DRD4).
      Genetic associations with six TMS measures and age at onset were investigated.
      Our hierarchical multiple regression analysis, controlling for CAG and age,
      revealed that a GABBR2 variant, predicted to be disease-causative, was
      significantly associated with corticospinal excitability at corrected levels. A
      subsequent uncorrected exploratory analysis revealed associations between GABBR2,
      GABRA2 and DRD2 variants with TMS measures of corticospinal excitability and
      cortical inhibition in HD, as well as with age at onset. Our findings support the
      notion that uncovering genetic associations with pathophysiological measures and
      age at onset is an important way forward in terms of generating meaningful
      biomarkers with diagnostic and prognostic sensitivity, and identifying novel
      human-validated targets for future clinical trials.

PMID- 27033669
TI  - Positive selection rather than relaxation of functional constraint drives the
      evolution of vision during chicken domestication.
AB  - As noted by Darwin, chickens have the greatest phenotypic diversity of all birds,
      but an interesting evolutionary difference between domestic chickens and their
      wild ancestor, the Red Junglefowl, is their comparatively weaker vision. Existing
      theories suggest that diminished visual prowess among domestic chickens reflect
      changes driven by the relaxation of functional constraints on vision, but the
      evidence identifying the underlying genetic mechanisms responsible for this
      change has not been definitively characterized. Here, a genome-wide analysis of
      the domestic chicken and Red Junglefowl genomes showed significant enrichment for
      positively selected genes involved in the development of vision. There were
      significant differences between domestic chickens and their wild ancestors
      regarding the level of mRNA expression for these genes in the retina. Numerous
      additional genes involved in the development of vision also showed significant
      differences in mRNA expression between domestic chickens and their wild
      ancestors, particularly for genes associated with phototransduction and
      photoreceptor development, such as RHO (rhodopsin), GUCA1A, PDE6B and NR2E3.
      Finally, we characterized the potential role of the VIT gene in vision, which
      experienced positive selection and downregulated expression in the retina of the
      village chicken. Overall, our results suggest that positive selection, rather
      than relaxation of purifying selection, contributed to the evolution of vision in
      domestic chickens. The progenitors of domestic chickens harboring weaker vision
      may have showed a reduced fear response and vigilance, making them easier to be
      unconsciously selected and/or domesticated.

PMID- 27033670
TI  - MLKL forms cation channels.
AB  - The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor
      necrosis factor-induced necroptosis. Recent studies on necroptosis execution
      revealed a commitment role of MLKL in membrane disruption. However, our knowledge
      of how MLKL functions on membrane remains very limited. Here we demonstrate that
      MLKL forms cation channels that are permeable preferentially to Mg(2+) rather
      than Ca(2+) in the presence of Na(+) and K(+). Moreover, the N-terminal domain
      containing six helices (H1-H6) is sufficient to form channels. Using the
      substituted cysteine accessibility method, we further determine that helix H1,
      H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the
      cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a
      positive correlation to its channel activity. The Mg(2+)-preferred permeability
      and five transmembrane segment topology distinguish MLKL from previously
      identified Mg(2+)-permeable channels and thus establish MLKL as a novel class of
      cation channels.

PMID- 27033671
TI  - Spontaneous resolution of an eosinophilic granuloma of the mandible following
      open biopsy.
AB  - Langerhans cell histiocytosis X is a clonal proliferation of dendritic cells of
      the immune system, which can affect multiple organ systems and range in behavior
      from a benign inflammatory process to a much more aggressive process. Only few
      isolated cases have been reported in the jaws. This case represents an example of
      Langerhans cell histiocytosis X in the mandible, which resolved following
      incisional biopsy without any further surgical intervention. 

PMID- 27033672
TI  - Cost-effectiveness of Gemcitabine Plus Modern Radiotherapy in Locally Advanced
      Pancreatic Cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of
      gemcitabine plus modern radiotherapy versus gemcitabine alone in the treatment of
      locally advanced pancreatic cancer in Taiwan. METHODS: A Markov decision-analytic
      model was performed to compare the cost-effectiveness of 3 treatment regimens;
      gemcitabine alone (gem-alone), gemcitabine plus intensity-modulated radiotherapy
      (gem-IMRT), and gemcitabine plus stereotactic body radiotherapy (gem-SBRT).
      Patients transitioned between 5 health states: stable disease, local progression,
      distant metastasis, local and distant metastasis, and death. FINDINGS: The
      incremental cost-effectiveness ratio for gem-IMRT and gem-SBRT compared with gem
      alone were NT$27,120,168 and NT$2,145,683 per quality-adjusted life-year gained,
      respectively. A willingness to pay threshold of 3 times the per capita gross
      domestic product was adopted according to the definition of the World Health
      Organization. The Taiwan per capita gross domestic product in 2015 was NT$673,920
      (US$22,464; 1 NT$ = US$0.03333 in Taiwan); thus, a threshold was considered as
      NT$2,021,760 (US$67,392). The Monte-Carlo simulation found that the probability
      of cost-effectiveness at a willingness to pay threshold of NT$2,021,760 per
      quality-adjusted life-year was 0% chance for gem-IMRT and 50% for gem-SBRT.
      IMPLICATIONS: This study indicated that gem-IMRT or gem-SBRT in locally advanced
      pancreatic cancer is not cost-effective at a willingness to pay as defined by
      World Health Organization guideline in Taiwan.

PMID- 27033673
TI  - Alleviation of temperature-sensitive secretion defect of Pseudomonas fluorescens
      ATP-binding cassette (ABC) transporter, TliDEF, by a change of single amino acid
      in the ABC protein, TliD.
AB  - An ABC transporter, TliDEF, from Pseudomonas fluorescens SIK W1, mediates the
      secretion of its cognate lipase, TliA, in a temperature-dependent secretion
      manner; the TliDEF-mediated secretion of TliA was impossible at the temperatures
      over 33 degrees C. To isolate a mutant TliDEF capable of secreting TliA at 35
      degrees C, the mutagenesis of ABC protein (TliD) was performed. The mutated tliD
      library where a random point mutation was introduced by error-prone PCR was
      coexpressed with the wild-type tliE, tliF and tliA in Escherichia coli. Among
      approximately 10,000 colonies of the tliD library, we selected one colony that
      formed transparent halo on LB-tributyrin plates at 35 degrees C. At the growth
      temperature of 35 degrees C, the selected mutant TliD showed 1.75 U/ml of the
      extracellular lipase activity, while the wild-type TliDEF did not show any
      detectable lipase activity in the culture supernatant of E. coli. Moreover, the
      mutant TliD also showed higher level of TliA secretion than the wild-type TliDEF
      at other culture temperatures, 20 degrees C, 25 degrees C and 30 degrees C. The
      mutant TliD had a single amino acid change (Ser287Pro) in the predicted
      transmembrane region in the membrane domain of TliD, implying that the
      corresponding region of TliD was important for causing the temperature-dependent
      secretion of TliDEF. These results suggested that the property of ABC transporter
      could be changed by the change of amino acid in the ABC protein. 

PMID- 27033674
TI  - Rhythm experience and Africana culture trial (REACT!): A culturally salient
      intervention to promote neurocognitive health, mood, and well-being in older
      African Americans.
AB  - The Rhythm Experience and Africana Culture Trial (REACT!) is a multi-site
      randomized controlled intervention study designed to examine the efficacy of
      using African Dance as a form of moderate-intensity physical activity to improve
      cognitive function in older African Americans. African Americans are almost two
      times more likely than Caucasians to experience cognitive impairment in late
      adulthood. This increased risk may be attributed to lower level and quality of
      education, lower socioeconomic status, and higher prevalence of vascular
      diseases, type 2 diabetes, hypertension, and obesity, all of which are recognized
      as risk factors for dementia. Fortunately, interventions targeting cardiovascular
      health (i.e., physical activity) are associated with improved neurocognitive
      function and a reduced risk for dementia, so African Americans may be
      particularly suited for interventions targeting cardiovascular health and
      cognitive function. Here, we describe a randomized intervention protocol for
      increasing physical activity in older (65-75years) African Americans.
      Participants (n=80) at two study locations will be randomized into one of two
      groups. The treatment group will participate in African Dance three times per
      week for six months and the control group will receive educational training on
      Africana history and culture, as well as information about health behaviors,
      three times per week for six months. If successful, the REACT! study may
      transform community interventions and serve as a platform and model for testing
      other populations, age groups, and health outcomes, potentially identifying novel
      and creative methods for reducing or eliminating health disparities.

PMID- 27033675
TI  - A refined definition improves the measurement reliability of the tip-apex
      distance.
AB  - BACKGROUND: Tip-apex distance (TAD) is reported as a good predictor for cut-outs
      of lag screws and spiral blades in the treatment of intertrochanteric fractures,
      and surgeons are advised to strive for TAD within 20 mm. However, the femoral
      neck axis and the position of the lower limb in the lateral radiograph are not
      clearly defined and can lead to measurement errors. We propose a refined TAD by
      defining these factors. The objective of this study was to analyze the
      reliability of this refined TAD. METHODS: The radiographs of 130 prospective
      cases with unstable trochanteric fractures were used for the analysis of the
      refined TAD. The refined TAD was independently measured by 2 raters with clinical
      experience of more than 10 years (rater 1, 2) and 2 raters with much less
      clinical experience (rater 3, 4) after they received a training about the new
      measurement method. Intraclass correlation coefficient (ICC [2,4]) was calculated
      to assess the interrater reliability. RESULTS: The mean refined TADs were
      18.2:18.4:18.2:18.2 mm for rater 1:2:3:4. There was a strong correlation among
      all four raters (ICC 0.998, (95% CI: 0.998, 0.999). CONCLUSIONS: Regardless of
      the clinical experience of raters, the refined TAD is a reliable tool and can be
      used to develop new TAD recommendations for predicting failure of fixation.
      Future studies with larger samples are needed to evaluate the predictive value of
      the refined TAD.

PMID- 27033676
TI  - A persistent antimicrobial resistance pattern and limited methicillin-resistance
      associated genotype in a short-term Staphylococcus aureus carriage isolated from
      a student population.
AB  - The aim of the present study was to assess and compare the antimicrobial
      susceptibility pattern against a panel of antibiotics and molecular and
      methicillin resistance-associated genotypes of 120 carriage S. aureus isolates
      previously isolated from a student population at two isolation events within a
      one-month interval. The antibiotic susceptibility of isolates was determined
      using the Kirby-Bauer disc-diffusion method (cefoxitin by Etest). The MRSA was
      screened using polymerase chain reaction for the presence of the mecA gene. The
      mecA-positive isolates were subjected to staphylococcal cassette chromosome (SCC)
      mec typing, multilocus sequence typing (MLST) and eBURST analysis. All isolates
      were characterized for the presence of the Panton-Valentine leukocidin (PVL)
      gene, an enterobacterial repetitive intergenic consensus-polymerase chain
      reaction (ERIC-PCR) pattern and the spa type. For the two occasions where S.
      aureus was isolated, the highest frequency of resistance was observed for
      penicillin (70% and 65%, respectively), with a lower rate against erythromycin
      and tetracycline (<12%). All isolates were susceptible to ciprofloxacin and
      gentamycin. As for methicillin resistance, eight isolates had minimum inhibitory
      concentrations (MIC) of resistant categories, but 10 isolates (8.33%) were
      positive for the mecA gene. The mecA-positive isolates belonged to SCCmec types I
      (n=9) and V (n=1). MLST was resolved for only three MRSAs, ST508 (n=1), ST88
      (n=1) and ST96 (n=1). The results of the eBURST analysis showed that the MRSA
      isolates analyzed in the present study were potentially related to MRSA
      identified in other countries. Approximately half of the persistent S. aureus
      carriers harbored S. aureus of a similar spa type in the respective individuals
      during both isolation events. A persistent antimicrobial pattern and limited
      distinct MRSAs were observed over the short study period. The latter frequently
      exhibited SCCmec type I, commonly associated with hospital-acquired (HA)
      characteristics, but further delineation is needed to justify the origins of
      these bacteria.

PMID- 27033677
TI  - A retrospective study of the epidemiology and clinical manifestation of invasive
      aspergillosis in a major tertiary care hospital in Bahrain.
AB  - Limited data are available on the epidemiology, clinical manifestations and
      outcomes of patients with invasive aspergillosis in Bahrain. This study was
      conducted retrospectively to determine the epidemiology of invasive aspergillosis
      and its risk factors, clinical presentation, underlying conditions, and outcomes
      over the past five years in a major hospital. The medical records of patients
      with positive Aspergillus cultures admitted to a major tertiary care hospital in
      Bahrain during 2009-2013 were reviewed. Cases were classified according to (1)
      the European Organization for the Research and Treatment of Cancer/Mycoses Study
      Group (MSG) criteria (proven, probable, possible IA or not classifiable) and (2)
      "validated" criteria to distinguish Aspergillus colonization from IA (putative or
      proven IA). Demographic, microbiologic and diagnostic data were collected, and
      outcomes were recorded. A total of 60 patients were included, of whom 44 were
      colonized (73.3%), and 16 had probable IA (26.7%); no proven or possible IA cases
      were identified according to the EORTC/Mycoses Study Group (MSG) criteria. In
      comparison, with the alternative "validated" criteria, 32 were colonized (53.3%),
      28 had putative IA (46.7%), and none had proven IA (0%). The lung was the most
      common site of infection, and Aspergillus fumigatus was the most commonly
      isolated species (53%). Mortality was 25% among colonized patients, 44% in
      probable cases and 32% in those with putative IA. All patients were
      immunocompromised or had one or more predisposing factors. Independent risk
      factors for death among patients with IA included older age, history of
      mechanical ventilation, renal replacement therapy and higher sequential organ
      failure assessment scores at diagnosis.

PMID- 27033679
TI  - Correction to Youssef et al., 2015.

PMID- 27033678
TI  - Suicide Among Refugees--A Mockery of Humanity.

PMID- 27033680
TI  - Obituary: Norman Farberow, 1918-2015.

PMID- 27033682
TI  - Space-by-time decomposition for single-trial decoding of M/EEG activity.
AB  - We develop a novel methodology for the single-trial analysis of multichannel time
      varying neuroimaging signals. We introduce the space-by-time M/EEG decomposition,
      based on Non-negative Matrix Factorization (NMF), which describes single-trial
      M/EEG signals using a set of non-negative spatial and temporal components that
      are linearly combined with signed scalar activation coefficients. We illustrate
      the effectiveness of the proposed approach on an EEG dataset recorded during the
      performance of a visual categorization task. Our method extracts three temporal
      and two spatial functional components achieving a compact yet full representation
      of the underlying structure, which validates and summarizes succinctly results
      from previous studies. Furthermore, we introduce a decoding analysis that allows
      determining the distinct functional role of each component and relating them to
      experimental conditions and task parameters. In particular, we demonstrate that
      the presented stimulus and the task difficulty of each trial can be reliably
      decoded using specific combinations of components from the identified space-by
      time representation. When comparing with a sliding-window linear discriminant
      algorithm, we show that our approach yields more robust decoding performance
      across participants. Overall, our findings suggest that the proposed space-by
      time decomposition is a meaningful low-dimensional representation that carries
      the relevant information of single-trial M/EEG signals.

PMID- 27033683
TI  - MRI of brain tissue oxygen tension under hyperbaric conditions.
AB  - The brain depends on a continuous supply of oxygen to maintain its structural and
      functional integrity. This study measured T1 from MRI under normobaric air,
      normobaric oxygen, hyperbaric air, and hyperbaric oxygen (HBO) conditions as a
      marker of tissue pO2 since dissolved molecular oxygen acts as an endogenous
      contrast agent. Brain tissue T1 decreased corresponding to increased pO2 with
      increasing inhaled oxygen concentrations, and tissue oxygenation was estimated
      from the T1 changes between different inhaled oxygen levels. Tissue pO2
      difference maps between different oxygen conditions showed heterogeneous pO2
      changes in the brain. MRI-derived tissue pO2 was markedly lower than the arterial
      pO2 but was slightly higher than venous pO2. Additionally, for comparison with
      published extracellular tissue pO2 data obtained using oxygen electrodes and
      other invasive techniques, a model was used to estimate extracellular and
      intracellular pO2 from the MRI-derived mean tissue pO2. This required multiple
      assumptions, and so the effects of the assumptions and parameters used in
      modeling brain pO2 were evaluated. MRI-derived pO2 values were strongly dependent
      on assumptions about the extra- and intracellular compartments but were
      relatively less sensitive to variations in the relaxivity constant of oxygen and
      contribution from oxygen in the cerebral blood compartment. This approach may
      prove useful in evaluating tissue oxygenation in disease states such as stroke.

PMID- 27033685
TI  - Complex interplay between brain function and structure during cerebral
      amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI
      comparison.
AB  - Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging
      population. Neuroimaging methods, in particular magnetic resonance imaging (MRI),
      have helped reveal alterations in the brain structure, metabolism, and function
      of patients and in groups at risk of developing AD, yet the nature of these
      alterations is poorly understood. Neuroimaging in mice is attractive for
      investigating mechanisms underlying functional and structural changes associated
      with AD pathology. Several preclinical murine models of AD have been generated
      based on transgenic insertion of human mutated APP genes. Depending on the
      specific mutations, mouse strains express different aspects of amyloid pathology,
      e.g. intracellular amyloid-beta (Abeta) aggregates, parenchymal plaques, or
      cerebral amyloid angiopathy. We have applied multi-parametric MRI in three
      transgenic mouse lines to compare changes in brain function with resting-state
      fMRI and structure with diffusion tensor imaging and high resolution anatomical
      imaging. E22DeltaAbeta developing intracellular Abeta aggregates did not present
      functional or structural alterations compared to their wild-type littermates.
      PSAPP mice displaying parenchymal amyloid plaques displayed mild functional
      changes within the supplementary and barrel field cortices, and increased
      isocortical volume relative to controls. Extensive reduction in functional
      connectivity in the sensory-motor cortices and within the default mode network,
      as well as local volume increase in the midbrain relative to wild-type have been
      observed in ArcAbeta mice bearing intracellular Abeta aggregates as well as
      parenchymal and vascular amyloid deposits. Patterns of functional and structural
      changes appear to be strain-specific and not directly related to amyloid
      deposition.

PMID- 27033686
TI  - Mindful attention to breath regulates emotions via increased amygdala-prefrontal
      cortex connectivity.
AB  - Mindfulness practice is beneficial for emotion regulation; however, the neural
      mechanisms underlying this effect are poorly understood. The current study
      focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice
      on aversive emotions at behavioral and brain levels. A key finding across
      different emotion regulation strategies is the modulation of amygdala and
      prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal
      cortex integrate with amygdala activation during emotional stimulation. We
      proposed that, during emotional stimulation, ATB down-regulates activation in the
      amygdala and increases its integration with prefrontal regions. To address this
      hypothesis, 26 healthy controls were trained in mindfulness-based attention-to
      breath meditation for two weeks and then stimulated with aversive pictures during
      both attention-to-breath and passive viewing while undergoing fMRI. Data were
      controlled for breathing frequency. Results indicate that (1) ATB was effective
      in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was
      associated with ATB in general. (3) A fronto-parietal network was additionally
      recruited during emotional stimulation. (4) ATB down regulated amygdala
      activation and increased amygdala-prefrontal integration, with such increased
      integration being associated with mindfulness ability. Results suggest amygdala
      dorsal prefrontal cortex integration as a potential neural pathway of emotion
      regulation by mindfulness practice.

PMID- 27033684
TI  - The effect of preprocessing pipelines in subject classification and detection of
      abnormal resting state functional network connectivity using group ICA.
AB  - Resting state functional network connectivity (rsFNC) derived from functional
      magnetic resonance (fMRI) imaging is emerging as a possible biomarker to identify
      several brain disorders. Recently it has been pointed out that methods used to
      preprocess head motion variance might not fully remove all unwanted effects in
      the data. Proposed processing pipelines locate the treatment of head motion
      effects either close to the beginning or as one of the final steps. In this work,
      we assess several preprocessing pipelines applied in group independent component
      analysis (gICA) methods to study the rsFNC of the brain. The evaluation method
      utilizes patient/control classification performance based on linear support
      vector machines and leave-one-out cross validation. In addition, we explored
      group tests and correlation with severity measures in the patient population. We
      also tested the effect of removing high frequencies via filtering. Two real data
      cohorts were used: one consisting of 48 mTBI and one composed of 21 smokers, both
      with their corresponding matched controls. A simulation procedure was designed to
      test the classification power of each pipeline. Results show that data
      preprocessing can change the classification performance. In real data, regressing
      motion variance before gICA produced clearer group differences and stronger
      correlation with nicotine dependence.

PMID- 27033687
TI  - Look who's judging-Feedback source modulates brain activation to performance
      feedback in social anxiety.
AB  - It is as yet unknown if behavioral and neural correlates of performance
      monitoring in socially anxious individuals are affected by whether feedback is
      provided by a person or a computer. This fMRI study investigated modulation of
      feedback processing by feedback source (person vs. computer) in participants with
      high (HSA) (N=16) and low social anxiety (LSA) (N=16). Subjects performed a
      choice task in which they were informed that they would receive positive or
      negative feedback from a person or the computer. Subjective ratings indicated
      increased arousal and anxiety in HSA versus LSA, most pronounced for social and
      negative feedback. FMRI analyses yielded hyperactivation in ventral medial
      prefrontal cortex (vmPFC)/anterior cingulate cortex (ACC) and insula for social
      relative to computer feedback, and in mPFC/ventral ACC for positive relative to
      negative feedback in HSA as compared to LSA. These activation patterns are
      consistent with increased interoception and self-referential processing in social
      anxiety, especially during processing of positive feedback. Increased ACC
      activation in HSA to positive feedback may link to unexpectedness of (social)
      praise as posited in social anxiety disorder (SAD) psychopathology. Activation in
      rostral ACC showed a reversed pattern, with decreased activation to positive
      feedback in HSA, possibly indicating altered action values depending on feedback
      source and valence. The present findings corroborate a crucial role of mPFC for
      performance monitoring in social anxiety.

PMID- 27033689
TI  - Impact of reading habit on white matter structure: Cross-sectional and
      longitudinal analyses.
AB  - Psychological studies showed the quantity of reading habit affects the
      development of their reading skills, various language skills, and knowledge.
      However, despite a vast amount of literature, the effects of reading habit on the
      development of white matter (WM) structures critical to language and reading
      processes have never been investigated. In this study, we used the fractional
      anisotropy (FA) measure of diffusion tensor imaging to measure WM microstructural
      properties and examined cross-sectional and longitudinal correlations between
      reading habit and FA of the WM bundles in a large sample of normal children. In
      both cross-sectional and longitudinal analyses, we found that greater strength of
      reading habit positively affected FA in the left arcuate fasciculus (AF), in the
      left inferior fronto-occipital fasciculus (IFOF), and in the left posterior
      corona radiata (PCR). Consistent with previous studies, we also confirmed the
      significance or a tendency for positive correlation between the strength of
      reading habit and the Verbal Comprehension score in cross-sectional and
      longitudinal analyses. These cross-sectional and longitudinal findings indicate
      that a healthy reading habit may be directly or indirectly associated with the
      advanced development of WM critical to reading and language processes. Future
      intervention studies are needed to determine the causal effects of reading habits
      on WM in normal children.

PMID- 27033688
TI  - The neural representation of objects formed through the spatiotemporal
      integration of visual transients.
AB  - Oftentimes, objects are only partially and transiently visible as parts of them
      become occluded during observer or object motion. The visual system can integrate
      such object fragments across space and time into perceptual wholes or
      spatiotemporal objects. This integrative and dynamic process may involve both
      ventral and dorsal visual processing pathways, along which shape and spatial
      representations are thought to arise. We measured fMRI BOLD response to
      spatiotemporal objects and used multi-voxel pattern analysis (MVPA) to decode
      shape information across 20 topographic regions of visual cortex. Object identity
      could be decoded throughout visual cortex, including intermediate (V3A, V3B, hV4,
      LO1-2,) and dorsal (TO1-2, and IPS0-1) visual areas. Shape-specific information,
      therefore, may not be limited to early and ventral visual areas, particularly
      when it is dynamic and must be integrated. Contrary to the classic view that the
      representation of objects is the purview of the ventral stream, intermediate and
      dorsal areas may play a distinct and critical role in the construction of object
      representations across space and time.

PMID- 27033691
TI  - Echocardiographic guidance for MitraClip implantation.

PMID- 27033690
TI  - Latex sensitization in patients with myelomeningocele undergoing urological
      procedures: prevalence and associated factors.

PMID- 27033693
TI  - Visual field defect classification in the Zhongshan Ophthalmic Center-Brien
      Holden Vision Institute High Myopia Registry Study.
AB  - PURPOSE: To describe a new combined myopia and glaucoma visual field
      classification system in order to report the visual field defects in a population
      of mostly young Chinese high myopes aged 7-70 years. METHODS: A total of 1434
      visual fields (including confirmatory repeats of abnormal defects) from 487 high
      myopes (sphere <=-6.0 D) were analysed from the prospective Zhongshan Ophthalmic
      Center-Brien Holden Vision Institute (ZOC-BHVI) High Myopia Registry Study. The
      predefined classification definitions covering high myopia and glaucoma
      categories were: normal, enlarged blind spot, abnormal suspect and abnormal with
      nine subtypes. Two independent graders reviewed the first 150 of 1434 fields for
      initial grading calibration and the remaining 1284 fields were used to assess
      intergrader agreement. For the percentage distribution of visual fields, the
      repeats and unreliable fields were excluded, leaving 894 fields. RESULTS: The
      intergrader agreement of this combined classification system was a kappa value of
      0.61 (95% CI 0.59 to 0.63). Among the 894 unique fields, the most common visual
      field was normal at 33.7% followed by enlarged blind spot at 25.6%. The per cent
      of 'arcuate-like' field defects (combining nasal step, early arcuate and advanced
      arcuate) was 16.1% with advanced arcuate at 3.4%. CONCLUSIONS: A proposed
      combined visual field classification for high myopia and glaucoma demonstrates
      acceptable intergrader agreement. A total of 16.1% of defects in young high
      myopes were found to mimic classic glaucomatous defects. These subjects are being
      followed prospectively to assess which ones will progress to differentiate myopic
      from glaucomatous field defects.

PMID- 27033694
TI  - Integrative bacterial artificial chromosomes for DNA integration into the
      Bacillus subtilis chromosome.
AB  - Bacillus subtilis is a well-characterized model bacterium frequently used for a
      number of biotechnology and synthetic biology applications. Novel strategies
      combining the advantages of B. subtilis with the DNA assembly and editing tools
      of Escherichia coli are crucial for B. subtilis engineering efforts. We combined
      Gibson Assembly and lambda red recombineering in E. coli with RecA-mediated
      homologous recombination in B. subtilis for bacterial artificial chromosome
      mediated DNA integration into the well-characterized amyE target locus of the B.
      subtilis chromosome. The engineered integrative bacterial artificial chromosome
      iBAC(cav) can accept any DNA fragment for integration into B. subtilis chromosome
      and allows rapid selection of transformants by B. subtilis-specific antibiotic
      resistance and the yellow fluorescent protein (mVenus) expression. We used the
      developed iBAC(cav)-mediated system to integrate 10kb DNA fragment from E. coli
      K12 MG1655 into B. subtilis chromosome. iBAC(cav)-mediated chromosomal
      integration approach will facilitate rational design of synthetic biology
      applications in B. subtilis.

PMID- 27033692
TI  - General health status and intelligence scores of children of mothers with
      acromegaly do not differ from those of healthy mothers.
AB  - PURPOSE: To determine the physical status and intelligence scores of children of
      acromegalic mothers and to compare them with those of children from mothers
      without acromegaly. METHODS: Six women with acromegaly who became pregnant under
      follow-up between 2010 and 2014 and their 16 children (group A) were assessed and
      compared with 16 children of healthy women (group B) and 15 children of women
      with prolactinoma (group C). The physical examinations of children were performed
      by the department of pediatric endocrinology and intelligence quotient (IQ)
      testing was undertaken by adult and pediatric psychiatry departments, using
      appropriate scales for their ages. RESULTS: Six of the 16 children (girls/boys:
      7/9) were born after the diagnosis of acromegaly. Five of the 6 pregnancies
      occured when the patients were taking somatostatin analogs, none continued taking
      the drugs during pregnancy. The mean IQ of groups A, B, and C were 106.4 +/-
      12.5, 105.3 +/- 12.5, and 103.2 +/- 16.1 respectively (p > 0.05). The mean ages,
      birth percentiles, recent weight and height standard deviation scores were
      similar between groups (p > 0.05). Two siblings from group A and 1 child from
      group B were large for gestational age at birth. At recent follow-up, two
      children from group A were found tall for their age and one from group C was
      short for his age and was placed under the care of pediatric endocrinology
      clinic. CONCLUSIONS: Pregnancies in acromegaly seems to be uneventful and the
      general health status and IQ scores of children from women with and without
      acromegaly were found similar.

PMID- 27033695
TI  - Switching Power Universality in Unipolar Resistive Switching Memories.
AB  - We investigate the resistive switching power from unipolar resistive switching
      current-voltage characteristics in various binary metal oxide films sandwiched by
      different metal electrodes, and find a universal feature (the so-called
      universality) in the switching power among these devices. To experimentally
      derive the switching power universality, systematic measurements of the switching
      voltage and current are performed, and neither of these correlate with one
      another. As the switching resistance (R) increases, the switching power (P)
      decreases following a power law P ? R(-beta), regardless of the device
      configurations. The observed switching power universality is indicative of the
      existence of a commonly applicable switching mechanism. The origin of the power
      universality is discussed based on a metallic filament model and thermo-chemical
      reaction. 

PMID- 27033696
TI  - Characterization of NADP(+)-dependent isocitrate dehydrogenase isozymes from a
      psychrophilic bacterium, Colwellia psychrerythraea strain 34H.
AB  - NADP(+)-dependent isocitrate dehydrogenase (IDH) isozymes of a psychrophilic
      bacterium, Colwellia psychrerythraea strain 34H, were characterized. The
      coexistence of monomeric and homodimeric IDHs in this bacterium was confirmed by
      Western blot analysis, the genes encoding two monomeric (IDH-IIa and IDH-IIb) and
      one dimeric (IDH-I) IDHs were cloned and overexpressed in Escherichia coli, and
      the three IDH proteins were purified. Both of the purified IDH-IIa and IDH-IIb
      were found to be cold-adapted enzymes while the purified IDH-I showed mesophilic
      properties. However, the specific activities of IDH-IIa and IDH-IIb were lower
      even at low temperatures than that of IDH-I. Therefore, IDH-I was suggested to be
      important for the growth of this bacterium. The results of colony formation of E.
      coli transformants carrying the respective IDH genes and IDH activities in their
      crude extracts indicated that the expression of the IDH-IIa gene is cold
      inducible in the E. coli cells. 

PMID- 27033697
TI  - Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials
      Based Drug Delivery Strategies.
AB  - The current epoch has witnessed a lifestyle impregnated with stress, which is a
      major cause of several neurological disorders. High morbidity and mortality rate
      due to neurological diseases and disorders have generated a huge social impact.
      Despite voluminous research, patients suffering from fatal and/or debilitating
      CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy,
      Parkinson's, migraine and multiple sclerosis outnumbered those suffering from
      systemic cancer or heart diseases. The brain being a highly sensitive neuronal
      organ, has evolved with vasculature barriers, which regulates the efflux and
      influx of substances to CNS. Treatment of CNS diseases/disorders is challenging
      because of physiologic, metabolic and biochemical obstacles created by these
      barriers which comprise mainly of BBB and BCFB. The inability of achieving
      therapeutically active concentration has become the bottleneck level difficulty,
      hampering the therapeutic efficiency of several promising drug candidates for CNS
      related disorders. Parallel maturation of an effective CNS drug delivery strategy
      with CNS drug discovery is the need of the hour. Recently, the focus of the
      pharmaceutical community has aggravated in the direction of developing novel and
      more efficient drug delivery systems, giving the potential of more effective and
      safer CNS therapies. The present review outlines several hurdles in drug delivery
      to the CNS along with ideal physicochemical properties desired in drug
      substance/formulation for CNS delivery. The review also focuses on different
      conventional and novel strategies for drug delivery to the CNS. The article also
      assesses and emphasizes on possible benefits of biomaterial based formulations
      for drug delivery to the CNS.

PMID- 27033698
TI  - Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine.
AB  - Chlamydia trachomatis is the most common cause of sexually transmitted bacterial
      infection globally. These infections translate to a significant public health
      burden, particularly women's healthcare costs due to serious disease sequelae
      such as pelvic inflammatory disease (PID), tubal factor infertility, chronic
      pelvic pain, and ectopic pregnancy. There is no evidence that natural immunity
      can provide complete, long-term protection necessary to prevent chronic
      pathology, making human vaccine development critical. Vaccine design will require
      careful consideration of protective versus pathological host-response mechanisms
      in concert with elucidation of optimal antigens and adjuvants. Evidence suggests
      that a Th1 response, facilitated by IFN-gamma-producing CD4 T cells, will be
      instrumental in generating long-term, sterilizing immunity. Although the role of
      antibodies is not completely understood, they have exhibited a protective effect
      by enhancing chlamydial clearance. Future work will require investigation of
      broadly neutralizing antibodies and antibody-augmented cellular immunity to
      successfully design a vaccine that potently elicits both arms of the immune
      response. Sterilizing immunity is the ultimate goal. However, vaccine-induced
      partial immunity that prevents upper genital tract infection and inflammation
      would be cost-effective compared to current screening and treatment strategies.
      In this chapter, we examine evidence from animal and human studies demonstrating
      protective adaptive immune responses to Chlamydia and discuss future challenges
      and prospects for vaccine development.

PMID- 27033699
TI  - Abdominoperineal resection and perineal wound healing in recurrent, persistent,
      or primary anal carcinoma.
AB  - PURPOSE: Chemoradiotherapy is the standard treatment for squamous cell anal
      cancer. Salvage abdominoperineal resection (APR) is usually reserved for patients
      presenting with recurrent or persistent disease. Aim of our study was to review
      the outcomes of salvage surgery and perineal wound healing with or without a
      vertical rectus abdominis myocutaneous (VRAM) flap in a single institution over a
      6-year period. METHODS: Data of all patients with biopsy-proven squamous cell
      anal cancer treated with chemoradiation at the University Medical Center Mannheim
      were recorded prospectively. Medical records of all patients who underwent
      salvage surgery for anal carcinoma between June 2008 and June 2014 were reviewed
      with regard to surgical and oncological outcomes. RESULTS: One hundred twenty
      four patients received chemoradiation with a 5-year overall survival of 79 %.
      Seventeen patients required (salvage) APR for recurrent (n = 8), persistent (n =
      7), or primary anal carcinoma (n = 2). Median overall survival was 33.4 months.
      Median duration until completion of perineal wound healing was shorter in the
      VRAM group (17 vs. 24.5 weeks; p = 0.0541). CONCLUSIONS: Salvage APR has a
      reasonable chance of long-time survival. Perineal reconstruction with a VRAM flap
      may reduce the duration until completion of perineal wound healing.

PMID- 27033700
TI  - Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of
      Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14.
AB  - The four tissue inhibitors of metalloproteinases (TIMPs) are potent inhibitors of
      the many matrixins (MMPs), except that TIMP1 weakly inhibits some MMPs, including
      MMP14. The broad-spectrum inhibition of MMPs by TIMPs and their N-domains
      (NTIMPs) is consistent with the previous isothermal titration calorimetric
      finding that their interactions are entropy-driven but differ in contributions
      from solvent and conformational entropy (DeltaSsolv, DeltaSconf), estimated using
      heat capacity changes (DeltaCp). Selective engineered NTIMPs have potential
      applications for treating MMP-related diseases, including cancer and
      cardiomyopathy. Here we report isothermal titration calorimetric studies of the
      effects of selectivity-modifying mutations in NTIMP1 and NTIMP2 on the
      thermodynamics of their interactions with MMP1, MMP3, and MMP14. The weak
      inhibition of MMP14 by NTIMP1 reflects a large conformational entropy penalty for
      binding. The T98L mutation, peripheral to the NTIMP1 reactive site, enhances
      binding by increasing DeltaSsolv but also reduces DeltaSconf However, the same
      mutation increases NTIMP1 binding to MMP3 in an interaction that has an unusual
      positive DeltaCp This indicates a decrease in solvent entropy compensated by
      increased conformational entropy, possibly reflecting interactions involving
      alternative conformers. The NTIMP2 mutant, S2D/S4A is a selective MMP1 inhibitor
      through electrostatic effects of a unique MMP-1 arginine. Asp-2 increases
      reactive site polarity, reducing DeltaCp, but increases conformational entropy to
      maintain strong binding to MMP1. There is a strong negative correlation between
      DeltaSsolv and DeltaSconf for all characterized interactions, but the data for
      each MMP have characteristic ranges, reflecting intrinsic differences in the
      structures and dynamics of their free and inhibitor-bound forms. 

PMID- 27033701
TI  - Molecular Basis of the Ligand Binding Specificity of alphavbeta8 Integrin.
AB  - alphavbeta8 is an integrin that recognizes an Arg-Gly-Asp (RGD) motif and
      interacts with fibronectin, vitronectin, and latent TGF-beta1. We comprehensively
      determined the binding activity of the alphavbeta8 integrin toward 25 secreted
      proteins having an RGD motif. The alphavbeta8 integrin strongly bound to latent
      TGF-beta1 but showed marginal activity for other RGD-containing proteins,
      including fibronectin and vitronectin. Site-directed mutagenesis of latent TGF
      beta1 demonstrated that the high affinity binding of alphavbeta8 integrin to
      latent TGF-beta1 was defined by Leu-218 immediately following the RGD motif
      within the latency-associated peptide of TGF-beta1. Consistent with the critical
      role of Leu-218 in latent TGF-beta1 recognition by alphavbeta8 integrin, a 9-mer
      synthetic peptide containing an RGDL sequence strongly inhibited interactions of
      latent TGF-beta1 with alphavbeta8 integrin, whereas a 9-mer peptide with an RGDA
      sequence was ~60-fold less inhibitory. Because alphavbeta3 integrin did not
      exhibit strong binding to latent TGF-beta1 or distinguish between RGDL- and RGDA
      containing peptides, we explored the mechanism by which the integrin beta8
      subunit defines the high affinity binding of latent TGF-beta1 by alphavbeta8
      integrin. Production of a series of swap mutants of integrin beta8 and beta3
      subunits indicated that the high affinity binding of alphavbeta8 integrin with
      latent TGF-beta1 was ensured by interactions between the Leu-218 residue and the
      beta8 I-like domain, with the former serving as an auxiliary recognition residue
      defining the restricted ligand specificity of alphavbeta8 integrin toward latent
      TGF-beta1. In support of this conclusion, high affinity binding toward the
      alphavbeta8 integrin was conferred on fibronectin by substitution of its RGDS
      motif with an RGDL sequence.

PMID- 27033702
TI  - Site-specific Acetylation of Histone H3 Decreases Polymerase beta Activity on
      Nucleosome Core Particles in Vitro.
AB  - Histone posttranslational modifications have been associated with changes in
      chromatin structure necessary for transcription, replication, and DNA repair.
      Acetylation is one of the most studied and best characterized histone
      posttranslational modifications, but it is not known if histone acetylation
      modulates base excision repair of DNA lesions in chromatin. To address this
      question, we generated nucleosome core particles (NCPs) containing site
      specifically acetylated H3K14 or H3K56 and measured repair of uracil and single
      nucleotide gaps. We find that H3K56Ac and H3K14Ac do not significantly contribute
      to removal of uracils by uracil DNA glycosylase regardless of the translational
      or rotational position of the lesions within NCPs. In repair of single-nucleotide
      gaps, however, the presence of H3K56Ac or H3K14Ac in NCPs decreases the gap
      filling activity of DNA polymerase beta near the dyad center, with H3K14Ac
      exhibiting stronger inhibition. To a lesser extent, H3K56Ac induces a similar
      effect near the DNA ends. Moreover, using restriction enzyme accessibility, we
      detect no changes in NCP structure or dynamics between H3K14Ac-NCPs and WT-NCPs
      containing single-nucleotide gaps. Thus, acetylation at H3K56 and H3K14 in
      nucleosomes may promote alternative gap-filling pathways by inhibiting DNA
      polymerase beta activity. 

PMID- 27033703
TI  - Lactation Is a Risk Factor of Postpartum Heart Failure in Mice with Cardiomyocyte
      specific Apelin Receptor (APJ) Overexpression.
AB  - The G protein-coupled receptor APJ and its ligand apelin are highly expressed in
      cardiovascular tissues and are associated with the regulation of blood pressure
      and cardiac function. Although accumulating evidence suggests that APJ plays a
      crucial role in the heart, it remains unclear whether up-regulation of APJ
      affects cardiac function. Here we generated cardiomyocyte-specific APJ
      overexpressing (APJ-TG) mice and investigated the cardiac phenotype in APJ-TG
      mice. Male and non-pregnant APJ-TG mice showed cardiac hypertrophy, contractile
      dysfunction, and elevation of B-type natriuretic peptide gene expression in the
      heart but not cardiac fibrosis and symptoms of heart failure, including breathing
      abnormality and pleural effusion. We further examined the influence of APJ
      overexpression in response to physiological stress induced by pregnancy and
      lactation in the heart. Interestingly, repeating pregnancy and lactation
      (pregnancy-lactation cycle) exacerbated cardiac hypertrophy and systolic
      dysfunction and induced cardiac fibrosis, lung congestion, pleural effusion, and
      abnormal breathing in APJ-TG mice. These data indicate that female APJ-TG mice
      develop postpartum cardiomyopathy. We showed that lactation, but not parturition,
      was critical for the onset of postpartum cardiomyopathy in APJ-TG mice.
      Furthermore, we found that lactating APJ-TG mice showed impaired myocardial
      angiogenesis and imbalance of pro- and antiangiogenic gene expression in the
      heart. These results demonstrate that overexpression of APJ in cardiomyocytes has
      adverse effects on cardiac function in male and non-pregnant mice and that
      lactation contributes to the development of postpartum cardiomyopathy in the
      heart with APJ overexpression. 

PMID- 27033704
TI  - Oxidative Stress and Nuclear Factor kappaB (NF-kappaB) Increase Peritoneal
      Filtration and Contribute to Ascites Formation in Nephrotic Syndrome.
AB  - Water accumulation in the interstitium (edema) and the peritoneum (ascites) of
      nephrotic patients is classically thought to stem from the prevailing low plasma
      albumin concentration and the decreased transcapillary oncotic pressure gradient.
      However, several clinical and experimental observations suggest that it might
      also stem from changes in capillary permeability. We addressed this hypothesis by
      studying the peritoneum permeability of rats with puromycin aminonucleoside
      induced nephrotic syndrome. The peritoneum of puromycin aminonucleoside rats
      displayed an increase in the water filtration coefficient of paracellular and
      transcellular pathways, and a decrease in the reflection coefficient to proteins.
      It also displayed oxidative stress and subsequent activation of NF-kappaB.
      Scavenging of reactive oxygen species and inhibition of NF-kappaB prevented the
      changes in the water permeability and reflection coefficient to proteins and
      reduced the volume of ascites by over 50%. Changes in water permeability were
      associated with the overexpression of the water channel aquaporin 1, which was
      prevented by reactive oxygen species scavenging and inhibition of NF-kappaB. In
      conclusion, nephrotic syndrome is associated with an increased filtration
      coefficient of the peritoneum and a decreased reflection coefficient to proteins.
      These changes, which account for over half of ascite volume, are triggered by
      oxidative stress and subsequent activation of NF-kappaB. 

PMID- 27033705
TI  - Nephrin Suppresses Hippo Signaling through the Adaptor Proteins Nck and WTIP.
AB  - Podocytes are key components of the kidney blood filtration barrier, and their
      ability to withstand hemodynamic strain is proposed to be closely tied to their
      unique and flexible cytoarchitecture. However, the mechanisms that control such
      mechanotransduction are poorly understood. We have previously established that
      tyrosine phosphorylation of the transmembrane protein nephrin promotes
      recruitment of the Nck1/2 cytoskeletal adaptor proteins and downstream actin
      remodeling. We now reveal that Nck integrates nephrin with the Hippo kinase
      cascade through association with the adaptor protein WTIP. Using mutational
      analysis, we show that Nck sequesters WTIP and its binding partner Lats1 to
      phosphorylated nephrin, resulting in decreased phospho-activation of Lats1. We
      further demonstrate that, coincident with nephrin dephosphorylation in a
      transient model of podocyte injury in mice, Lats1 is rapidly activated, and this
      precedes significant down-regulation of the transcription regulator Yap.
      Moreover, we show reduced levels of Yap protein in mice with chronic disruption
      of nephrin phospho-signaling. Together, these findings support the existence of a
      dynamic molecular link between nephrin signaling and the canonical Hippo pathway
      in podocytes, which may facilitate the conversion of mechanical cues to
      biochemical signals promoting podocyte viability.

PMID- 27033707
TI  - One operator's experience of ultrasound guided lumbar plexus block for paediatric
      hip surgery.
AB  - Lumbar plexus block has been shown to be effective for providing postoperative
      analgesia after major hip surgeries in children. The goal of the study was to
      evaluate the feasibility of ultrasound guidance during lumbar plexus block in
      children undergoing hip surgery for congenital hip dislocation. After obtaining
      local institutional ethical committee approval and parental informed consent, ASA
      I or II, 1-6 years old children undergoing hip surgery were included into the
      study. Lumbar plexus block was performed after general anaesthesia using
      ultrasound guided Shamrock Method. Bupivacaine 0.25 % was used during block
      performance. Dose of the local anaesthetic was 1 ml/kg and the maximum dose was
      limited to 20 ml. In the postoperative period pain was assessed using modified
      CHEOPS (Children's Hospital Eastern Ontario Pain Scale) pain score. If pain score
      in the postoperative period exceeded 3, patients received IV paracetamol 15 mg/kg
      1. Morphine 0.1 mg/kg-1 IV was planned to administer if pain scores were still
      higher than 3 despite paracetamol treatment. 75 patients whose mean age was 47
      months were enrolled into the study. All blocks were performed successfully and
      without complications. Mean time for the first analgesic is found as 10 h after
      surgery. Only one patient required morphine in the recovery unit and 23 patients
      received paracetamol. US guided lumbar plexus block using Shamrock Method is an
      effective technique for providing postoperative analgesia after hip surgeries in
      children and it's effect lasts for 8-12 h after surgery.

PMID- 27033708
TI  - Identifying and individuating cognitive systems: a task-based distributed
      cognition alternative to agent-based extended cognition.
AB  - This article argues for a task-based approach to identifying and individuating
      cognitive systems. The agent-based extended cognition approach faces a problem of
      cognitive bloat and has difficulty accommodating both sub-individual cognitive
      systems ("scaling down") and some supra-individual cognitive systems ("scaling
      up"). The standard distributed cognition approach can accommodate a wider variety
      of supra-individual systems but likewise has difficulties with sub-individual
      systems and faces the problem of cognitive bloat. We develop a task-based variant
      of distributed cognition designed to scale up and down smoothly while providing a
      principled means of avoiding cognitive bloat. The advantages of the task-based
      approach are illustrated by means of two parallel case studies: re-representation
      in the human visual system and in a biomedical engineering laboratory. 

PMID- 27033706
TI  - Divergent Evolution of Nuclear Localization Signal Sequences in Herpesvirus
      Terminase Subunits.
AB  - The tripartite terminase complex of herpesviruses assembles in the cytoplasm of
      infected cells and exploits the host nuclear import machinery to gain access to
      the nucleus, where capsid assembly and genome-packaging occur. Here we analyzed
      the structure and conservation of nuclear localization signal (NLS) sequences
      previously identified in herpes simplex virus 1 (HSV-1) large terminase and human
      cytomegalovirus (HCMV) small terminase. We found a monopartite NLS at the N
      terminus of large terminase, flanking the ATPase domain, that is conserved only
      in alpha-herpesviruses. In contrast, small terminase exposes a classical NLS at
      the far C terminus of its helical structure that is conserved only in two genera
      of the beta-subfamily and absent in alpha- and gamma-herpesviruses. In addition,
      we predicted a classical NLS in the third terminase subunit that is partially
      conserved among herpesviruses. Bioinformatic analysis revealed that both location
      and potency of NLSs in terminase subunits evolved more rapidly than the rest of
      the amino acid sequence despite the selective pressure to keep terminase gene
      products active and localized in the nucleus. We propose that swapping NLSs among
      terminase subunits is a regulatory mechanism that allows different herpesviruses
      to regulate the kinetics of terminase nuclear import, reflecting a mechanism of
      virus:host adaptation. 

PMID- 27033709
TI  - Group-Based Trajectory Modeling of Suppression Ratio After Cardiac Arrest.
AB  - BACKGROUND: Existing studies of quantitative electroencephalography (qEEG) as a
      prognostic tool after cardiac arrest (CA) use methods that ignore the
      longitudinal pattern of qEEG data, resulting in significant information loss and
      precluding analysis of clinically important temporal trends. We tested the
      utility of group-based trajectory modeling (GBTM) for qEEG classification,
      focusing on the specific example of suppression ratio (SR). METHODS: We included
      comatose CA patients hospitalized from April 2010 to October 2014, excluding CA
      from trauma or neurological catastrophe. We used Persyst(r)v12 to generate SR
      trends and used semi-quantitative methods to choose appropriate sampling and
      averaging strategies. We used GBTM to partition SR data into different
      trajectories and regression associate trajectories with outcome. We derived a
      multivariate logistic model using clinical variables without qEEG to predict
      survival, then added trajectories and/or non-longitudinal SR estimates, and
      assessed changes in model performance. RESULTS: Overall, 289 CA patients had >=36
      h of EEG yielding 10,404 h of data (mean age 57 years, 81 % arrested out-of
      hospital, 33 % shockable rhythms, 31 % overall survival, 17 % discharged to home
      or acute rehabilitation). We identified 4 distinct SR trajectories associated
      with survival (62, 26, 12, and 0 %, P < 0.0001 across groups) and CPC (35, 10, 4,
      and 0 %, P < 0.0001 across groups). Adding trajectories significantly improved
      model performance compared to adding non-longitudinal data. CONCLUSIONS:
      Longitudinal analysis of continuous qEEG data using GBTM provides more predictive
      information than analysis of qEEG at single time-points after CA.

PMID- 27033710
TI  - Poor outcome is associated with less negative fluid balance in patients with
      aneurysmal subarachnoid hemorrhage treated with prophylactic vasopressor-induced
      hypertension.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a serious condition
      associated with high mortality rates and long-term disability. We investigated
      the impact of fluid balance on neurologic outcome after adjustment for possible
      confounders related to intensive care therapy and extra-cerebral organ failure
      during the early phase after SAH. METHODS: In this retrospective study, we
      analyzed data from all 142 adult patients admitted to our university hospital
      surgical intensive care unit (ICU) with SAH between March 2004 and November 2010.
      RESULTS: The mean patient age was 54 +/- 14 years, 62.7 % were female, and the
      median Hunt and Hess score was 3. The proportions of patients with poor outcome
      (Glasgow Outcome Score <=3) were 58.4, 54.2, and 52.1 % at 3, 6, and 12 months,
      respectively, after the SAH. The ICU and hospital mortality rates were both 12.7
      %, and the median lengths of stay in the ICU and the hospital were 16 (IQ 7-25)
      and 26 (IQ 18-34) days, respectively. In multivariable analysis, older age and
      greater cumulative fluid balance within the first 7 days in the ICU were
      independently associated with a greater risk of poor outcome. CONCLUSION: In this
      cohort of patients, older age and greater cumulative fluid balance were
      independently associated with a greater risk of poor outcome up to 1 year after
      the initial insult. Our data suggest that mild hypovolemia may be beneficial in
      the management of these patients.

PMID- 27033711
TI  - Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia:
      a prospective, randomised trial.
AB  - BACKGROUND: Cases of ventilator-associated pneumonia (VAP) due to multidrug
      resistant (MDR) gram-negative bacilli (GNB) mainly Acinetobacter baumannii,
      Pseudomonas aeruginosa and enterobacteria are common in hospitalised patients of
      Tunisian intensive care units (ICUs). Parenteral colistin has been used for the
      therapy of VAP caused by MDR GNB at Tunisian hospitals over the past few years
      with a favourable clinical response. However, its use fell out of favour because
      of the reported drug-related nephrotoxicity and neurotoxicity. OBJECTIVES: To
      determine whether aerosolised (AS) colistin was beneficial and safe in therapy of
      gram-negative VAP. METHODS: This was a randomised, single-blind study, in 149
      critically ill adults who developed gram-negative VAP. Included patients were
      divided into two groups whether they received AS colistin (intervention group; n
      = 73) or intravenous (IV) colistin (control group; n = 76). AS colistin was given
      as 4 million units (MU) by nebulisation three times per 24 h. IV colistin was
      given as a loading dose of 9 MU followed by 4.5 MU two times per 24 h. Patients
      were followed during 28 days. Primary outcome was cure of VAP assessed at day 14
      of therapy and defined as resolution of clinical signs of VAP and bacteriological
      eradication. Secondary outcomes were incidence of acute renal failure (ARF),
      mechanical ventilation length, ICU length of stay and 28-day mortality. Results
      were analysed based on intention-to-treat concept. RESULTS: The patient's
      baseline characteristics and distribution of pathogens VAP in both groups were
      similar. The clinical cure rate was 67.1 % in AS group and 72 % in IV group (p =
      0.59). When administered in monotherapy or in combination, the AS regimen was as
      effective as IV regimen. Patients in AS group had significantly lower incidence
      of ARF (17.8 vs 39.4 %, p = 0.004), more favourable improvement of P/F ratio (349
      vs 316 at day 14, p = 0.012), shortened time to bacterial eradication (TBE) (9.89
      vs 11.26 days, p = 0.023) and earlier weaning from ventilator in ICU survivors
      with a mean gain in ventilator-free days of 5 days. No difference was shown in
      the length of stay and the 28-day mortality. CONCLUSION: Aerosolised colistin
      seems to be beneficial. It provided a therapeutic effectiveness non-inferior to
      parenteral colistin in therapy of MDR bacilli VAP with a lower nephrotoxicity, a
      better improvement of P/F ratio, a shortened bacterial eradication time and
      earlier weaning from ventilator in ICU survivors. Trial registration
      ClinicalTrials.gov Identifier: NCT02683603.

PMID- 27033712
TI  - Understanding the formation of supported lipid bilayers via vesicle fusion-A case
      that exemplifies the need for the complementary method approach (Review).
AB  - In this review, the authors discuss the challenges of studying supported lipid
      bilayers (SLBs) deposited by vesicle fusion in terms of (1) evaluating SLB
      formation and quality using quartz crystal microbalance with dissipation and (2)
      analyzing the composition and asymmetry of SLBs composed by lipid mixtures using
      complementary surface sensitive techniques. An overview of the literature is
      presented and the inconsistencies on this topic are discussed with the objective
      to expand beyond simple lipid compositions and set the basis for forming and
      analyzing SLBs of complex natural lipid extracts formed via the vesicle fusion
      method. The authors conclude by providing some guidelines to successfully form
      SLBs of complex lipid mixtures including natural extracts. 

PMID- 27033713
TI  - Two-color pupillometry in enhanced S-cone syndrome caused by NR2E3 mutations.
AB  - PURPOSE: The purpose of this study was to evaluate pupillary light reflexes
      (PLRs) mediated by rod, cone, and intrinsically photosensitive retinal ganglion
      cell pathways as indices of outer- and inner-retinal function in patients who
      have enhanced S-cone syndrome (ESCS) due to NR2E3 mutations. METHODS: Four
      patients with ESCS (ages 16-23 years) participated in the study. Subjects were
      tested with long- and short-wavelength single-flash full-field ERG stimuli under
      light-adapted conditions. They were also tested with an established pupillometry
      protocol involving 1-s duration, long- and short-wavelength stimuli under dark-
      and light-adapted conditions. The PLR was measured as a function of stimulus
      luminance. Transient PLRs were measured under all conditions, and sustained PLRs
      were measured under the highest luminance dark-adapted condition. RESULTS: Two
      color light-adapted full-field ERGs demonstrated larger amplitude responses for
      short-wavelength stimuli relative to long-wavelength stimuli of the same photopic
      luminance, with three of four ESCS patients having super-normal a-wave amplitudes
      to the short-wavelength stimulus. b/a wave ratios were reduced in all four cases.
      Transient PLRs elicited by low-luminance stimuli under dark-adapted conditions
      (rod-mediated) were unrecordable, whereas the sustained PLRs elicited by high
      luminance stimuli (melanopsin-mediated) were normal. Cone-mediated PLRs were
      recordable for all four patients, but generally lower than normal in amplitude.
      However, the cone-mediated PLR was larger for the short-wavelength stimulus
      compared to the photopically matched long-wavelength stimulus at high luminances,
      a pattern that was not observed for control subjects. None of the PLR conditions
      demonstrated "super-normal" responses. CONCLUSION: ESCS patients appear to have
      generally well-preserved cone- and melanopsin-mediated PLRs, indicating intact
      inner-retinal function. Two-color pupillometry demonstrates greater sensitivity
      to short-wavelength light under higher-luminance conditions and could complement
      the ERG as a tool for evaluating retinal function in ESCS.

PMID- 27033714
TI  - Enhanced biodegradation of antibiotic combinations via the sequential treatment
      of the sludge resulting from pharmaceutical wastewater treatment using white-rot
      fungi Trametes versicolor and Bjerkandera adusta.
AB  - While anaerobic treatment is capable of treating pharmaceutical wastewater and
      removing antibiotics in liquid phases, solid phases may still contain significant
      amounts of antibiotics following this treatment. The main goal of this study was
      to evaluate the use of white-rot fungi to remove erythromycin, sulfamethoxazole,
      and tetracycline combinations from biosolids. The degradation potential of
      Trametes versicolor and Bjerkandera adusta was evaluated via the sequential
      treatment of anaerobic sludge. Polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE) analyses were used to identify competition between the
      autochthonous microbial communities and white-rot fungi. Solid-phase treatment
      using white-rot fungi substantially reduced antibiotic concentrations and
      toxicity in sludge. According to PCR-DGGE results, there is an association
      between species of fungus and antibiotic type as a result of the different
      transformation pathways of fungal strains. Fungal post-treatment of sludge
      represents a promising method of removing antibiotic combinations, therefore
      holding a significant promise as an environmentally friendly means of degrading
      the antibiotics present in sludge. 

PMID- 27033715
TI  - Design of evidence-based gardens and garden therapy for neurodisability in
      Scandinavia: data from 14 sites.
AB  - AIM: A total of 14 Scandinavian therapy gardens were visited and data collected
      on plantings, therapeutic activities and assessment of effectiveness in Spring
      2014. METHODOLOGY: Data were gathered by a questionnaire and by interviewing
      staff in Sweden, Denmark and Norway. The data collection structured proforma used
      the post-occupation assessment method. RESULTS: Gardening promoted physical
      movement, presented cognitive challenges and provided opportunities for social
      participation. Half the gardens were enclosed with sensory plants and 85% were
      adapted for wheelchairs. A total of 57% of gardens visited had simple designs
      with flowers, shrubs, lawns and trees. A social center was important especially
      for dementia clients. Planted pots were used in 79% of gardens. The effectiveness
      of therapy gardens was assessed at 71% of sites.

PMID- 27033716
TI  - Prognosis for term breech presentations in Africa (Bobo Dioulasso, Burkina Faso).
AB  - to describe the mode of delivery and the fetal prognosis for breech presentations
      in Bobo Dioulasso, Burkina Faso. this prospective, descriptive, cross-sectional
      study covered the entire year 2013 and included patients from the city's three
      principal maternity units. The sample included 184 women who gave birth at term
      to fetuses in breech presentation and a control group of 368 women with infants
      in cephalic presentation. Data were collected with standardized case report
      forms. The analysis was conducted with Epi-Info 3.5.1 software. We used the Chi
      square test to compare percentages and the Chi-square test for trend to study the
      variation in frequencies. Differences were considered significant when P <= 0.05.
      during the study period, the prevalence of breech presentation at term was 1.74%.
      In the breech group, 55.5% of the women had vaginal deliveries versus 92% in the
      cephalic group (P = 0.04). The comparative analysis of fetal and neonatal
      morbidity in the two groups found greater morbidity in the breech group, marked
      by complications including uterine rupture (P = 0.0045), cord prolapse (P =
      0.02), dynamic dystocia (P = 0.001), fetal distress (P = 0.0001), postpartum
      hemorrhage (P = 0.003), and perinatal death (P = 0.006). vaginal delivery remains
      the most frequent mode of delivery for breech presentations in Bobo Dioulasso,
      and perinatal morbidity and mortality are relatively high. Improvement of
      hospital protocols and staff training for breech deliveries should help to
      improve this situation. 

PMID- 27033717
TI  - Heat Management in Thermoelectric Power Generators.
AB  - Thermoelectric power generators are used to convert heat into electricity. Like
      any other heat engine, the performance of a thermoelectric generator increases as
      the temperature difference on the sides increases. It is generally assumed that
      as more heat is forced through the thermoelectric legs, their performance
      increases. Therefore, insulations are typically used to minimize the heat losses
      and to confine the heat transport through the thermoelectric legs. In this paper
      we show that to some extend it is beneficial to purposely open heat loss channels
      in order to establish a larger temperature gradient and therefore to increase the
      overall efficiency and achieve larger electric power output. We define a modified
      Biot number (Bi) as an indicator of requirements for sidewall insulation. We show
      cooling from sidewalls increases the efficiency for Bi values less than one, and
      decreases the efficiency for Bi values larger than one. 

PMID- 27033718
TI  - Phase transitions via selective elemental vacancy engineering in complex oxide
      thin films.
AB  - Defect engineering has brought about a unique level of control for Si-based
      semiconductors, leading to the optimization of various opto-electronic properties
      and devices. With regard to perovskite transition metal oxides, O vacancies have
      been a key ingredient in defect engineering, as they play a central role in
      determining the crystal field and consequent electronic structure, leading to
      important electronic and magnetic phase transitions. Therefore, experimental
      approaches toward understanding the role of defects in complex oxides have been
      largely limited to controlling O vacancies. In this study, we report on the
      selective formation of different types of elemental vacancies and their
      individual roles in determining the atomic and electronic structures of
      perovskite SrTiO3 (STO) homoepitaxial thin films fabricated by pulsed laser
      epitaxy. Structural and electronic transitions have been achieved via selective
      control of the Sr and O vacancy concentrations, respectively, indicating a
      decoupling between the two phase transitions. In particular, O vacancies were
      responsible for metal-insulator transitions, but did not influence the Sr vacancy
      induced cubic-to-tetragonal structural transition in epitaxial STO thin film. The
      independent control of multiple phase transitions in complex oxides by exploiting
      selective vacancy engineering opens up an unprecedented opportunity toward
      understanding and customizing complex oxide thin films.

PMID- 27033719
TI  - Expressed emotion in panic disorder: Relationship with demographic and clinical
      variables and quality of life.
AB  - OBJECTIVE: Expressed emotion (EE) predicts the outcome of treatment in patients
      with anxiety disorders. We aimed to investigate the relationship between EE and
      demographic and clinical characteristics of patients with panic disorder (PD), to
      determine whether there is a difference between PD, major depressive disorder
      (MDD) patients and healthy controls (HC) in terms of EE and to investigate the
      effect of EE on quality of life (QOL) in patients with PD. METHODS: Our study
      involved a total of 150 participants (50 patients in each group). All
      participants were given the Level of Expressed Emotion (LEE) scale and the short
      form health survey (SF)-36 . Furthermore, the EE scale was completed by the
      participant's key relatives. RESULTS: EE was associated with some
      sociodemographic and clinical variables in patients with PD. There was no
      significant difference between PD and MDD and between PD and HC in terms of the
      LEE and the EE and their subscale scores. It was also demonstrated that EE had no
      effect on the QOL in patients with PD. CONCLUSION: EE was not different in PD
      compared to MDD and HC. Additionally, EE was not related to QOL in PD.

PMID- 27033720
TI  - Spatial variation in senescence rates in a bird metapopulation.
AB  - Investigating factors which affect the decline in survival with age, i.e.
      actuarial senescence, is important in order to understand how demographic rates
      vary in wild populations. Although the evidence for the occurrence of actuarial
      senescence in wild populations is growing, very few studies have compared
      actuarial senescence rates between wild populations of the same species. We used
      data from a long-time study of demography of house sparrows (Passer domesticus)
      to investigate differences in rates of actuarial senescence between habitats and
      sub-populations. We also investigated whether rates of actuarial senescence
      differed between males and females. We found that rates of actuarial senescence
      showed large spatial variation. We also found that the onset of actuarial
      senescence varied between sub-populations. However, these differences were not
      significantly explained by a general difference in habitat type. We also found no
      significant difference in actuarial senescence rates between males and females.
      This study shows that senescence rates in natural populations may vary
      significantly between sub-populations and that failing to account for such
      differences may give a biased estimate of senescence rates of a species.

PMID- 27033721
TI  - [Management of prosthetic joint infections].
AB  - Infections of prosthetic joints with biofilm-forming pathogens are one of the
      most devastating complications for patients and surgeons. Although the incidence
      is low they result in massive restrictions in the quality of life and mobility
      for patients as well as high costs for the treatment. Crucial for an adequate
      management of prosthetic joint infections are primarily comprehensive diagnostics
      to be able to exclude an aseptic loosening and secondarily in the presence of an
      infection to identify the pathogen responsible for forming the biofilm. The
      correct grading of the infection is crucial for selecting the appropriate form of
      infection management. Established standards in surgical treatment as well as in
      microbiology have be considered. 

PMID- 27033722
TI  - Hispanic Acculturation and Gender Differences in Support and Self-Efficacy for
      Managing Diabetes.
AB  - PURPOSE: The purpose of this study was to determine whether perceived support,
      social norms, and their association with self-efficacy varied by gender and
      language-based acculturation in Hispanic men and women with uncontrolled type 2
      diabetes mellitus (T2DM). METHODS: A cross-sectional, secondary analysis of
      baseline survey data from a randomized control trial. Participants were 248
      Hispanic patients from 4 community health centers who participated in a
      culturally targeted intervention for diabetes management. Quantitative
      statistical methods were used, including chi-square analyses, one-way ANOVA, and
      multiple regression. RESULTS: Gender and language both moderated the relationship
      between social factors and self-efficacy. Regardless of language, better
      perceived support was associated with improved self-efficacy in women but not
      men. Dietary norms were associated with self-efficacy in English-speaking men and
      women, while physical activity norms were associated with self-efficacy for
      Spanish-speaking women only. CONCLUSIONS: This study builds on previous research
      by exploring the extent to which the social context of diabetes self-management
      may vary in its effects depending on gender and acculturation. The findings
      revealed potentially important differences based on both gender and language,
      suggesting that interventions must be designed with these differences in mind.
      Diabetes-specific support from family members, especially spouses, may be
      especially important for Hispanic women. For both men and women, it may be
      effective to find creative ways of involving the family in creating healthier
      social norms and expectations.

PMID- 27033723
TI  - Changes in Body Weight Among People With Type 2 Diabetes Mellitus in the United
      States, NHANES 2005-2012.
AB  - PURPOSE: To understand weight loss strategies, weight changes, goals, and
      behaviors in people with type 2 diabetes mellitus (T2DM) and whether these differ
      by ethnicity. METHODS: T2DM was identified by self-reported diagnosis using the
      NHANES 2005-2012 data, which also included measured and self-reported current
      body weight and height, self-reported weight the prior year, and self-reported
      aspired weight. Nineteen weight loss strategies were evaluated for association
      with >=5% weight loss or weight gain versus <5% weight change. RESULTS: Among
      people with T2DM, 88.0% were overweight/obese (body mass index [BMI] >=25
      kg/m(2)) in the prior year and 86.1% the current year. About 60% of the
      overweight/obese took weight loss actions, mostly using diet-related methods with
      average weight lost <5%. Two most "effective" methods reported (smoking, taking
      laxatives/vomiting) are also potentially most harmful. Similar BMI distributions
      but different goals and behaviors about weight and weight loss were observed
      across ethnicity. Only physical activity meeting the recommended level and
      changing eating habits were consistently associated with favorable and
      statistically significant weight change. CONCLUSIONS: Weight management in T2DM
      is an ongoing challenge, regardless of ethnicity/race. Among overweight/obese
      T2DM subjects, recommended level of physical activity and changing eating habits
      were associated with statistically significant favorable weight change.

PMID- 27033725
TI  - Novartis wined and dined doctors at 80,000 "sham events" to increase prescribing,
      US alleges.

PMID- 27033724
TI  - Targeted disruption of influenza A virus hemagglutinin in genetically modified
      mice reduces viral replication and improves disease outcome.
AB  - Influenza A virus can cause acute respiratory infection in animals and humans
      around the globe, and is still a major threat to animal husbandry and public
      health. Due to antigenic drift and antigenic shift of the virus, development of
      novel anti-influenza strategies has become an urgent task. Here we generated
      transgenic (TG) mice stably expressing a short-hairpin RNA specifically targeting
      hemagglutinin (HA) of influenza A virus, and investigated the susceptibility of
      the mice to influenza virus infection. We found that HA expression was
      dramatically disrupted in TG mice infected with WSN or PR8 virus. Importantly,
      the animals showed reduced virus production in lungs, slower weight loss,
      attenuated acute organ injury and consequently increased survival rates as
      compared to wild type (WT) mice after the viral infection. Moreover, TG mice
      exhibited a normal level of white blood cells following the virus infection,
      whereas the number of these cells was significantly decreased in WT mice with
      same challenge. Together, these experiments demonstrate that the TG mice are less
      permissive for influenza virus replication, and suggest that shRNA-based
      efficient disruption of viral gene expression in animals may be a useful strategy
      for prevention and control of a viral zoonosis. 

PMID- 27033727
TI  - Peripherin-2 differentially interacts with cone opsins in outer segments of cone
      photoreceptors.
AB  - Peripherin-2 is a glycomembrane protein exclusively expressed in the light
      sensing compartments of rod and cone photoreceptors designated as outer segments
      (OS). Mutations in peripherin-2 are associated with degenerative retinal diseases
      either affecting rod or cone photoreceptors. While peripherin-2 has been
      extensively studied in rods, there is only little information on its
      supramolecular organization and function in cones. Recently, we have demonstrated
      that peripherin-2 interacts with the light detector rhodopsin in OS of rods. It
      remains unclear, however, if peripherin-2 also binds to cone opsins. Here, using
      a combination of co-immunoprecipitation analyses, transmission electron
      microscopy (TEM)-based immunolabeling experiments, and quantitative fluorescence
      resonance energy transfer (FRET) measurements in cone OS of wild type mice, we
      demonstrate that peripherin-2 binds to both, S-opsin and M-opsin. However, FRET
      based quantification of the respective interactions indicated significantly less
      stringent binding of peripherin-2 to S-opsin compared to its interaction with M
      opsin. Subsequent TEM-studies also showed less co-localization of peripherin-2
      and S-opsin in cone OS compared to peripherin-2 and M-opsin. Furthermore,
      quantitative FRET analysis in acutely isolated cone OS revealed that the cone
      degeneration-causing V268I mutation in peripherin-2 selectively reduced binding
      to M-opsin without affecting the peripherin-2 interaction to S-opsin or
      rhodopsin. The differential binding of peripherin-2 to cone opsins and the mutant
      specific interference with the peripherin-2/M-opsin binding points to a novel
      role of peripherin-2 in cones and might contribute to understanding the
      differential penetrance of certain peripherin-2 mutations in rods and cones.
      Finally, our results provide a proof-of-principle for quantitative FRET
      measurements of protein-protein interactions in cone OS.

PMID- 27033728
TI  - High resolution bone material property assignment yields robust subject specific
      finite element models of complex thin bone structures.
AB  - Accurate finite element (FE) modeling of complex skeletal anatomy requires high
      resolution in both meshing and the heterogeneous mapping of material properties
      onto the generated mesh. This study introduces Node-based elastic Modulus
      Assignment with Partial-volume correction (NMAP) as a new approach for FE
      material property assignment to thin bone structures. The NMAP approach
      incorporates point spread function based deblurring of CT images, partial-volume
      correction of CT image voxel intensities and anisotropic interpolation and
      mapping of CT intensity assignment to FE mesh nodes. The NMAP procedure combined
      with a derived craniomaxillo-facial skeleton (CMFS) specific density-isotropic
      elastic modulus relationship was applied to produce specimen-specific FE models
      of 6 cadaveric heads. The NMAP procedure successfully generated models of the
      complex thin bone structures with surface elastic moduli reflective of cortical
      bone material properties. The specimen-specific CMFS FE models were able to
      accurately predict experimental strains measured under in vitro temporalis and
      masseter muscle loading (r=0.93, slope=1.01, n=5). The strength of this
      correlation represents a robust validation for CMFS FE modeling that can be used
      to better understand load transfer in this complex musculoskeletal system. The
      developed methodology offers a systematic process-flow able to address the
      complexity of the CMFS that can be further applied to create high-fidelity models
      of any musculoskeletal anatomy.

PMID- 27033726
TI  - A multi-ethnic genome-wide association study identifies novel loci for non
      syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.
AB  - Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without
      cleft palate (CL/P), are among the most common birth defects in humans, affecting
      approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a
      complex etiology caused by genetic and environmental factors. Previous genome
      wide association studies (GWASs) have identified at least 15 risk loci for CL/P.
      As these loci do not account for all of the genetic variance of CL/P, we
      hypothesized the existence of additional risk loci. We conducted a multiethnic
      GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319
      case-parent trios) with European, Asian, African and Central and South American
      ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of
      unknown function (P = 4.22 * 10-8), and 19q13 near RHPN2, a gene involved in
      organizing the actin cytoskeleton (P = 4.17 * 10-8). Other regions reaching
      genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and
      17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group
      revealed a novel association with a region on 17q23 (P = 2.92 * 10-8) among
      individuals with European ancestry. This region included several promising
      candidates including TANC2, an oncogene required for development, and DCAF7, a
      scaffolding protein required for craniofacial development. In the Central and
      South American ancestry group, significant associations with loci previously
      identified in Asian or European ancestry groups reflected their admixed ancestry.
      In summary, we have identified novel CL/P risk loci and suggest new genes
      involved in craniofacial development, confirming the highly heterogeneous
      etiology of OFCs.

PMID- 27033729
TI  - Multiphasic modeling of charged solute transport across articular cartilage:
      Application of multi-zone finite-bath model.
AB  - Charged and uncharged solutes penetrate through cartilage to maintain the
      metabolic function of chondrocytes and to possibly restore or further breakdown
      the cartilage tissue in different stages of osteoarthritis. In this study the
      transport of charged solutes across the various zones of cartilage was
      quantified, taken into account the physicochemical interactions between the
      solute and the cartilage constituents. A multiphasic finite-bath finite element
      (FE) model was developed to simulate equine cartilage diffusion experiments that
      used a negatively charged contrast agent (ioxaglate) in combination with serial
      micro-computed tomography (micro-CT) to measure the diffusion. By comparing the
      FE model with the experimental data both the diffusion coefficient of ioxaglate
      and the fixed charge density (FCD) were obtained. In the multiphasic model,
      cartilage was divided into multiple (three) zones to help understand how
      diffusion coefficient and FCD vary across cartilage thickness. The direct effects
      of charged solute-FCD interaction on diffusion were investigated by comparing the
      diffusion coefficients derived from the multiphasic and biphasic-solute models.
      We found a relationship between the FCD obtained by the multiphasic model and
      ioxaglate partitioning obtained from micro-CT experiments. Using our multi-zone
      multiphasic model, diffusion coefficient of the superficial zone was up to ten
      fold higher than that of the middle zone, while the FCD of the middle zone was up
      to almost two-fold higher than that of the superficial zone. In conclusion, the
      developed finite-bath multiphasic model provides us with a non-destructive method
      by which we could obtain both diffusion coefficient and FCD of different
      cartilage zones. The outcomes of the current work will also help understand how
      charge of the bath affects the diffusion of a charged molecule and also predict
      the diffusion behavior of a charged solute across articular cartilage.

PMID- 27033730
TI  - Phylogenetic Analyses of Three Genes of Pedinomonas noctilucae, the Green
      Endosymbiont of the Marine Dinoflagellate Noctiluca scintillans, Reveal its
      Affiliation to the Order Marsupiomonadales (Chlorophyta, Pedinophyceae) under the
      Reinstated Name Protoeuglena noctilucae.
AB  - In the last decade, field studies in the northern Arabian Sea showed a drastic
      shift from diatom-dominated phytoplankton blooms to thick and widespread blooms
      of the green dinoflagellate, Noctiluca scintillans. Unlike the exclusively
      heterotrophic red form, which occurs widely in tropical to temperate coastal
      waters, the green Noctiluca contains a large number of endosymbiotic algal cells
      that can perform photosynthesis. These symbiotic microalgae were first described
      under the genus Protoeuglena Subrahmanyan and further transferred to Pedinomonas
      as P. noctilucae Sweeney. In this study, we used the 18S rDNA, rbcL and
      chloroplast 16S rDNA as gene markers, in combination with the previously reported
      morphological features, to re-examine the phylogenetic position of this
      endosymbiotic algal species. Phylogenetic trees inferred from these genes
      consistently indicated that P. noctilucae is distantly related to the type
      species of Pedinomonas. The sequences formed a monophyletic clade sister to the
      clade of Marsupiomonas necessitating the placement of the algal symbionts as an
      independent genus within the family Marsupiomonadaceae. Based on the phylogenetic
      affiliation and ecological characteristics of this alga as well as the priority
      rule of nomenclature, we reinstate the genus Protoeuglena and reclassify the
      endosymbiont as Protoeuglena noctilucae.

PMID- 27033731
TI  - Persulfate initiated ultra-low cross-linked poly(N-isopropylacrylamide) microgels
      possess an unusual inverted cross-linking structure.
AB  - Cross-linking density and distribution are decisive for the mechanical and other
      properties of stimuli-sensitive poly(N-isopropylacrylamide) microgels. Here we
      investigate the structure of ultra-low cross-linked microgels by static light
      scattering and scanning force microscopy, and show that they have an inverted
      cross-linking structure with respect to conventional microgels, contrary to what
      has been assumed previously. The conventional microgels have the largest polymer
      volume fraction in the core from where the particle density decays radially
      outwards, whereas ultra-low cross-linked particles have the highest polymer
      volume fraction close to the surface. On a solid substrate these particles form
      buckled shapes at high surface coverage, as shown by scanning force micrographs.
      The special structure of ultra-low cross-linked microgels is attributed to cross
      linking of the particle surface, which is exposed to hydrogen abstraction by
      radicals generated from persulfate initiators during and after polymerization.
      The particle core, which is less accessible to the diffusion of radicals, has
      consequently a lower polymer volume fraction in the swollen state. By systematic
      variation of the cross-linker concentration it is shown that the cross-linking
      contribution from peroxide under typical synthesis conditions is weaker than that
      from the use of 1 mol% N,N'-methylenebisacrylamide. Soft deformable hydrogel
      particles are of interest because they emulate biological tissues, and
      understanding the underlying synthesis principle enables tailoring the microgel
      structure for biomimetic applications. Deformability of microgels is usually
      controlled by the amount of added cross-linker; here we however highlight an
      alternative approach through structural softness.

PMID- 27033732
TI  - Electron-phonon coupling in Ni-based binary alloys with application to
      displacement cascade modeling.
AB  - Energy transfer between lattice atoms and electrons is an important channel of
      energy dissipation during displacement cascade evolution in irradiated materials.
      On the assumption of small atomic displacements, the intensity of this transfer
      is controlled by the strength of electron-phonon (el-ph) coupling. The el-ph
      coupling in concentrated Ni-based alloys was calculated using electronic
      structure results obtained within the coherent potential approximation. It was
      found that Ni0.5Fe0.5, Ni0.5Co0.5 and Ni0.5Pd0.5 are ordered ferromagnetically,
      whereas Ni0.5Cr0.5 is nonmagnetic. Since the magnetism in these alloys has a
      Stoner-type origin, the magnetic ordering is accompanied by a decrease of
      electronic density of states at the Fermi level, which in turn reduces the el-ph
      coupling. Thus, the el-ph coupling values for all alloys are approximately 50%
      smaller in the magnetic state than for the same alloy in a nonmagnetic state. As
      the temperature increases, the calculated coupling initially increases. After
      passing the Curie temperature, the coupling decreases. The rate of decrease is
      controlled by the shape of the density of states above the Fermi level.
      Introducing a two-temperature model based on these parameters in 10 keV molecular
      dynamics cascade simulation increases defect production by 10-20% in the alloys
      under consideration. 

PMID- 27033733
TI  - Outcomes of cases with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency -
      Report from the Inborn Errors of Metabolism Information System.
AB  - INTRODUCTION: 3-Methyl crotonyl CoA carboxylase (3MCC) deficiency is an inborn
      error of leucine metabolism whose detection was increased with the advent of
      expanded newborn screening. While most NBS-identified infants appear clinically
      normal, prior studies suggest a possible increased risk for developmental or
      metabolic abnormalities. As yet, no predictive markers are known that can
      identify children at risk for biochemical or developmental abnormalities. METHOD:
      All available 3-MCC cases diagnosed by newborn screening in the Inborn Errors of
      Metabolism Information System (IBEM-IS) were reviewed for markers that might be
      predictive of outcome. RESULTS: A limited number of cases were identified with
      traditional biochemical symptoms including acidosis, hyperammonemia or lactic
      acidosis, and 15% of those with available developmental information had recorded
      developmental disabilities not clearly attributable to other causes. There was no
      correlation between newborn screening (NBS) C5OH level and presence of metabolic,
      newborn, later-life or developmental abnormalities in these cases. DISCUSSION:
      This sample, obtained from the IBEM-IS database, attempts to avoid some of the
      ascertainment bias present in retrospective studies. An increase in developmental
      abnormalities and in traditionally described metabolic symptoms remains apparent,
      although no specific biochemical markers appear predictive of outcome. The role
      that prevention of fasting plays in outcome cannot be ascertained. These data
      suggest that C5OH level found on newborn screening by itself is not sufficient
      for diagnostic or predictive purposes.

PMID- 27033734
TI  - Synthesis and biological evaluation of novel 2-phenylquinazoline-4-amine
      derivatives: identification of 6-phenyl-8H-benzo[g]quinazolino[4,3-b]quinazolin-8
      one as a highly potent inducer of NAD(P)H quinone oxidoreductase 1.
AB  - A novel series of quinazoline compounds (2-14) incorporating biologically active
      heterocyclic moieties were designed and synthesized. The structure of the newly
      synthesized compounds was recognized on the basis of elemental analyses, IR, 1H
      NMR, 13C-NMR and mass spectral data. All compounds were evaluated for their
      ability to induce the cytoprotective enzyme NAD(P)H:quinone oxidoreductase 1
      (NQO1) using a quantitative bioassay and a docking study was performed in the
      Kelch domain of Keap1 obtained from the Protein Data Bank (PDB ID: 4IQK) to
      explore the ability of the synthesized compounds to block the Nrf2-binding site
      of Keap1. All of the synthesized compounds showed concentration-dependent inducer
      activity with potencies in the low- or sub-micromolar range. Compound 12 was the
      most potent inducer in this new series, with a concentration that doubles the
      specific activity of NQO1 (CD value) of 70 nM. The identification of this
      compound offers a new chemical scaffold for future development of highly potent
      inducers.

PMID- 27033735
TI  - Costs of living: weighing the numerous variables involved.

PMID- 27033736
TI  - Comparison between systemic and catheter thrombolysis in patients with pulmonary
      embolism.
AB  - BACKGROUND: Although systemic thrombolysis (ST) or catheter-directed therapy
      (CDT) is performed in patients with acute massive or submassive pulmonary
      embolism (PE), clinical data comparing between both therapies remain limited. We
      compared clinical outcomes between ST and CDT in patients with acute massive and
      submassive PE. METHODS: From January 2005 to June 2015, clinical outcomes of
      patients with acute massive or submassive PE receiving ST or CDT were evaluated
      and compared retrospectively. RESULTS: Of 72 patients, 44 were treated with ST;
      and 28, with CDT. The mean age was 63.9 +/- 17 years old. The proportion of male
      sex was higher in patients receiving CDT compared to that with ST (46.4% vs
      20.5%; P = .02). Half of patients presented with massive PE, and cardiac arrest
      occurred in 11 patients (15.3%). No difference was observed between the 2 groups
      with respect to 7-day mortality (13.6% in ST vs 10.7% in CDT), inhospital
      mortality (13.6% in ST vs 14.3% in CDT), and major bleeding complication (16.7%
      in ST vs 16.7% in CDT). Cardiac arrest (odds ratio, 6.286; 95% confidence
      interval, 1.081-36.555; P = .041) was associated with 14-day mortality.
      CONCLUSIONS: Similar clinical outcomes were shown between ST and CDT in patients
      with acute massive or submassive PE.

PMID- 27033737
TI  - Comparison of NIO and EZ-IO intraosseous access devices in adult patients under
      resuscitation performed by paramedics: a randomized crossover manikin trial.

PMID- 27033738
TI  - An unusual cause of acute chest pain: rupture of the noncoronary sinus of
      Valsalva into the right atrium.

PMID- 27033739
TI  - Meta-analysis of outcomes of the 2005 and 2010 cardiopulmonary resuscitation
      guidelines for adults with in-hospital cardiac arrest.
AB  - OBJECTIVES: The post-cardiac arrest survival rate has remained low since the 2010
      cardiopulmonary resuscitation (CPR) guidelines were published. The present study
      aimed to review the 2010 vs 2005 CPR guideline outcomes in adults with in
      hospital cardiac arrest. METHODS: The Pub Med, EMBASE, and Cochrane Library
      databases were searched for articles published between January 2006 and July
      2015. We extracted the following from observational studies and intervention
      studies: first author's name, publication year, study duration, age of study
      population, and sample size. The primary outcome variables were return of
      spontaneous circulation (ROSC) and survival to discharge. The data were divided
      into 2005 (data collected before December 2010) and 2010 (data collected in
      December 2010 or later) CPR guidelines groups. RESULTS: Twenty-four original
      articles (77,605 patients) were included. Statistically significant heterogeneity
      (ROSC: P<.01, I(2)=97.9%; survival to discharge: P<.01, I(2)=98.3%) was seen, and
      a random-effects model was used to pool the outcomes. The pooled ROSC rate for
      the 2010 group (n=5; mean, 48%; 95% confidence interval [CI], 0.38-0.58) was only
      slightly higher than that of the 2005 group (n=19; mean, 47%; 95% CI, 0.38-0.57).
      The opposite result was noted in the pooled survival to discharge rates (2010:
      n=5, mean, 14%; 95% CI, 0.08-0.20 vs 2005: n=19; mean, 15%; 95% CI, 0.10-0.20).
      There was actually no significant difference in ROSC or survival to discharge
      outcomes between the 2 groups. CONCLUSIONS: The 2010 CPR guidelines emphasized
      that high-quality chest compressions can increase the ROSC rate but did not show
      to improve long-term results.

PMID- 27033740
TI  - Zinc attenuates ethanol-induced Sertoli cell toxicity and apoptosis through
      caspase-3 mediated pathways.
AB  - Ethanol enhances apoptosis in testicular germ cells. Zinc reduces ethanol-induced
      apoptosis of somatic cells through inhibition of caspase-mediated pathways.
      Little is known about the effects of ethanol on Sertoli cells and the effects of
      Zinc on ethanol-induced testicular injury. The hypothesis tested was that ethanol
      enhances apoptosis of Sertoli cells through up-regulation of caspase-3 and Zinc
      inhibits ethanol-induced effects. Cultured Sertoli cells (TM4) were exposed to
      ethanol (160mM), Zinc (8MUM) and Zinc prior to ethanol for duration of 24 or 48h
      and their effects on TM4 cell viability was then investigated by MTT assay.
      Caspase-3 mRNA expression was also investigated using real-time RT-PCR. Cell
      viability decreased and caspase-3 mRNA expresstion increased in cells exposed to
      ethanol, while exposure to Zinc showed opposite effects. Pretreatment with Zinc
      recovered ethanol-induced anti-proliferative effects and over-expression of
      caspase-3. Zinc reduced ethanol-induced Sertoli cell toxicity and apoptosis via
      caspase-3 mediated pathways.

PMID- 27033741
TI  - The impact of stress on motor performance in skilled musicians suffering from
      focal dystonia: Physiological and psychological characteristics.
AB  - Recent investigations have suggested that stress can modulate motor function.
      However, the impact of stress on motor performance of musicians suffering from
      focal dystonia (FDM) remains unknown. The current study assessed motor
      performance in 20 FDM patients and 16 healthy musicians (HM) before and under
      stress. Stress was manipulated using the Trier Social Stress Test (TSST). Motor
      performance was evaluated based on analysis of electromyographic (EMG) activity
      and temporal variability, while electrocardiography (ECG) and the level of free
      cortisol were used to test for objective alterations of the hypothalamic
      pituitary-adrenal (HPA) axis. Finally, the psychological profiles of both groups
      were analyzed using three psycho-diagnostic standardized questionnaires. Results
      showed that patients' motor impairments did not change under acute stressful
      conditions. However, an increase in muscular co-contractions was observed,
      reflecting a physiological muscular response under stressful conditions. Psycho
      diagnostic analysis revealed higher levels of psychological traits related to
      elevated anxiety, stress and perfectionism in 40% of the patients. Although the
      motor outcome between those patients and those with an opposing psychological
      profile did not differ, patients characterized by stressful and perfectionistic
      personalities had, on average, developed dystonia about ten years earlier than
      the rest of the patients. The current study suggests that acute stress conditions
      may not have any direct impact on fine motor control of FDM patients. However
      psychological traits associated with increased stress, anxiety and perfectionism
      may have a long-lasting effect on the motor function of affected musicians, by
      promoting the acceleration or even the triggering of dystonia.

PMID- 27033742
TI  - Associative memory and underlying brain correlates in older adults with mild
      cognitive impairment.
AB  - This study investigated associative recognition memory by using unique features
      of the Chinese language and the underlying neuroanatomical correlates. The study
      participants were 22 Chinese speakers with mild cognitive impairment (MCI) and 25
      cognitively normal (CN) Chinese speakers. The results revealed that the MCI group
      demonstrated impaired associative memory performance, despite exhibiting item
      memory performance comparable with that of the CN group, and that associative
      memory performance in older adults was associated with gray matter integrity in
      the medial temporal regions as well as executive function. An abnormal elevation
      was also observed in false-positive errors related to features unique to Chinese
      characters, namely orthographical errors, in addition to rearranged and semantic
      errors in the MCI group relative to the CN group, and the three error subtypes
      were differentially associated with gray matter integrity in the hippocampus or
      lateral prefrontal regions. Overall, these results demonstrate the value of
      evaluating associative memory in people with prodromal Alzheimer's disease (AD),
      and further elucidate the underlying neural substrates related to associative
      recognition memory in older adults.

PMID- 27033743
TI  - Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting
      Pathogen Transmission.
AB  - Preventing pathogen transmission to a new host is of major interest to the
      immunologist and could benefit from a detailed investigation of pathogen immune
      evasion strategies. The first line of defense against pathogen invasion is
      provided by macrophages. When they sense pathogens, macrophages initiate signals
      to inflammatory and pro-inflammatory cytokines through pattern recognition
      receptors (PRRs) subsequently mediating phagocytosis and inflammation. The
      macrophage immune machinery classically includes two subsets: the activated M1
      and the activated M2 that respond accordingly in diverse immune challenges. The
      lipid and glycogen metabolic pathways work together with the lysosome to help the
      mature phagosome to degrade and eliminate intracellular pathogens in macrophages.
      The viral evasion strategies are even more complex due to the interplay between
      autophagy and apoptosis. However, pathogens evolve several strategies to
      camouflage themselves against immune responses in order to ensure their survival,
      replication and transmission. These strategies include the muting of PRRs
      initiated inflammatory responses, attenuation of M1 and/or induction of M2
      macrophages, suppression of autophago-lysosomal formation, interference with
      lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis
      cross-talk to enhance viral replication. This review focuses on pathogen immune
      evasion methods and on the strategies used by the host against camouflaged
      pathogens.

PMID- 27033744
TI  - Acute cholangitis: An unexpected cause of fever of unknown origin diagnosed by
      (18)F-FDG PET/CT.

PMID- 27033745
TI  - (18)F-FDG PET/CT in a case of primary hepatic adenosquamous carcinoma.

PMID- 27033746
TI  - Age-specific percentile-based reference curve of serum procalcitonin
      concentrations in Japanese preterm infants.
AB  - Procalcitonin (PCT) levels are elevated early after birth in newborn infants;
      however, the physiological features and reference of serum PCT concentrations
      have not been fully studied in preterm infants. The aims of the current study
      were to establish an age-specific percentile-based reference curve of serum PCT
      concentrations in preterm infants and determine the features. The PCT
      concentration peaked in infants at 1 day old and decreased thereafter. At 1 day
      old, serum PCT concentrations in preterm infants <34 weeks' gestational age were
      higher than those in late preterm infants between 34 and 36 weeks' gestational
      age or term infants >=37 weeks' gestational age. Although the 50-percentile value
      in late preterm and term infants reached the adult normal level (0.1 ng/mL) at 5
      days old, it did not in preterm infants. It took 9 weeks for preterm infants to
      reach it. Serum PCT concentrations at onset in late-onset infected preterm
      infants were over the 95-percentile value. We showed that the physiological
      feature in preterm infants was significantly different from that in late preterm
      infants, even in those <37 weeks' gestational age. To detect late-onset bacterial
      infection and sepsis, an age-specific percentile-based reference curve may be
      useful in preterm infants. 

PMID- 27033747
TI  - Impact of non-medical switching on clinical and economic outcomes, resource
      utilization and medication-taking behavior: a systematic literature review.
AB  - OBJECTIVE: To evaluate current knowledge of the impact of non-medical switching
      on clinical and economic outcomes, resource utilization and medication-taking
      behavior. METHODS: The literature was searched (Medline and Web of Science,
      January 2000-November 2015) to identify United States' studies evaluating >=25
      patients and measuring the impact of non-medical switching of drugs (switching to
      a chemically distinct but similar medication for reasons other than lack of
      clinical efficacy/response, side effects or poor adherence) on >=1 clinical,
      economic, resource utilization or medication-taking behavior outcome. The
      direction of association between non-medical switching and outcomes was
      classified as negative or positive if a statistically significant worsening or
      improvement was reported, or neutral if no significant difference was observed.
      RESULTS: Twenty-nine studies contributed 96 outcomes (60.4% clinical; 21.9%
      resource utilization; 13.5% economic; 4.2% medication-taking behavior) within six
      disease categories (cardio-metabolic, immune-mediated, acid suppression,
      psychiatric, hormone replacement therapy and pain). The direction of association
      was more frequently negative (33.3%) or neutral (55.2%) than it was positive
      (11.5%). Stratified by outcome type, non-medical switching was negatively
      associated with clinical, economic, healthcare utilization and medication-taking
      behavior outcomes in 20.7%, 69.2%, 38.1% and 75.0% of cases, respectively; and
      positively in only 4.8%-17.2% of outcomes subgroups. Of 32 outcomes in patients
      demonstrating stable/well controlled disease, 68.8% and 31.3% had a negative and
      neutral direction of association. In patients without demonstrated disease
      stability, outcomes were negatively, neutrally and positively impacted by non
      medical switching in 15.6%, 67.2% and 17.2% of 64 outcomes. LIMITATIONS: Our
      inability to evaluate specific disease state categories and studies/outcomes
      received equal weight regardless of sample size or magnitude of effect.
      CONCLUSIONS: Non-medical switching was more often associated with negative or
      neutral effects than positive effects on an array of important outcomes. Among
      patients with stable/well controlled disease, non-medical switching was
      associated with mostly negative effects.

PMID- 27033748
TI  - [Syringomas].

PMID- 27033749
TI  - [Aplasia cutis congenita and antithyroid drugs during pregnancy: Case series and
      literature review].
AB  - BACKGROUND: Aplasia cutis congenita (ACC) following in utero exposure to
      antithyroid drugs such as methimazole/carbimazole (MTZ/CMZ) has been reported
      since 1972. Though currently included in MTZ/CMZ embryopathy, it remains poorly
      characterized and is little discussed. Having seen two cases within a short
      period of time, we carried out a literature review and searched the French
      pharmacovigilance database for notification of cases. PATIENTS AND METHODS: We
      performed a search of the literature in the Medline database using the following
      keywords: "aplasia cutis congenita", "birth skin defects", "pregnancy" and
      "drug". All articles reporting cases of ACC following in utero exposure to
      antithyroid drugs were included. All cases of ACC under antithyroid drugs
      reported to French pharmacovigilance centres were analysed. RESULTS: Three
      hundred and sixty-eight articles were retrieved and 31 were analysed, including a
      further 4, mentioned in selected articles, giving 59 cases of ACC under MTZ/CMZ
      reported in the literature and having an intrinsic accountability score of
      plausible or dubious. ACC was typically isolated, single, small in size, and
      localised on the median scalp area. Exposure occurred in the first weeks of
      gestation. There were 6 familial cases involving siblings. Ten ACC and MTZ/CMZ
      cases were reported to pharmacovigilance centres in France. DISCUSSION:
      Practitioners should be aware of ACC following MTZ/CMZ exposure in utero, whether
      it occurs in isolation or not. It is likely a teratogenic effect of MTZ/CMZ
      enhanced by a genetic predisposition.

PMID- 27033750
TI  - Image of an extensive aneurysm in a young patient.

PMID- 27033751
TI  - Multispecies reassortant bovine rotavirus strain carries a novel simian G3-like
      VP7 genotype.
AB  - Rotavirus-A (RVAs), are the major cause of severe gastroenteritis in the young of
      mammals and birds. RVA strains possessing G6, G8, and G10 genotypes in
      combination with P[1] or P[11] have been commonly detected in cattle. During a
      routine surveillance for enteric viruses in a bovine population on North-Western
      temperate Himalayan region of India, an uncommon bovine RVA strain, designated as
      RVA/Cow-wt/IND/M1/09/2009 was detected in a diarrhoeic crossbred calf. The
      examination of nearly complete genome sequence of this RVA strain revealed an
      unusual G-P combination (G3P[11]) on a typical bovine RVA genotype backbone (I2
      R2-C2-M2-A11-N2-T6-E2-H3). The VP7 gene of M1/09 isolate displayed a maximum
      nucleotide sequence identity of 73.8% with simian strain (RVA/Simian
      tc/USA/RRV/1975/G3P[3]). The VP4 and NSP5 genes clustered with an Indian pig
      strain, RVA/Pig-wt/IND/AM-P66/2012/G10P[11] (99.6%), and a caprine strain,
      RVA/Goat-tc/BGD/GO34/1999/G6P[1] (98.9%) from Bangladesh, respectively, whilst
      the, VP6, NSP1, NSP3 and NSP4 genes were identical or nearly identical to Indian
      bovine strains (RVA/Cow-wt/IND/B-72/2008/G10P[X], RVA/Cow-wt/IND/B85/2010/GXP[X],
      and RVA/Cow-wt/IND/C91/2011/G6P[X]). The remaining four genes (VP1, VP2, VP3 and
      NSP2) were more closely related to RVA/Human-wt/ITA/PAI11/1996/G2P[4] (93.5%),
      RVA/Sheep-wt/CHN/LLR/1985/G10P[15] (88.8%), RVA/Human-tc/SWE/1076/1983/G2P2A[6]
      (93.2%) and RVA/Human-wt/AUS/CK20003/2000/G2P[4] (91.2%), respectively.
      Altogether, these findings are suggestive of multiple independent interspecies
      transmission and reassortment events between co-circulating bovine, porcine,
      ovine and human rotaviruses. The complete genome sequence information is
      necessary to establish the evolutionary relationship, interspecies transmission
      and ecological features of animal RVAs from different geographical regions.

PMID- 27033752
TI  - [Epidemiology of febrile neutropenia in patients with hematological disease-a
      prospective multicentre survey in China].
AB  - OBJECTIVE: To investigate the incidence, clinical and microbiological features of
      febrile, and risk factors during neutropenia periods in patients with
      hematological diseases. METHODS: From October 20, 2014 to March 20, 2015,
      consecutive patients who had hematological diseases and developed neutropenia
      during hospitalization were enrolled in the prospective, multicenter and
      observational study. RESULTS: A total of 784 episodes of febrile occurred in 1
      139 neutropenic patients with hematological diseases. The cumulative incidence of
      febrile was 81.9% at 21 days after neutropenia. Multivariate analysis suggested
      that central venous catheterization (P<0.001, HR=3.407, 95% CI 2.276-4.496),
      gastrointestinal mucositis (P<0.001, HR=10.548, 95% CI 3.245-28.576), previous
      exposure to broad-spectrum antibiotics within 90 days (P<0.001, HR=3.582, 95% CI
      2.387-5.770) and duration of neutropenia >7 days (P<0.001,HR=4.194, 95% CI 2.572
      5.618) were correlated with higher incidence of febrile during neutropenia. With
      the increase of the risk factors, the incidence of febrile increased gradually
      (35.4%, 69.2%, 86.1%, 95.6%, P<0.001). Of 784 febrile cases, 253 (32.3%) were
      unknown origin, 429 (54.7% )of clinical documented infections and 102(13.0%) of
      microbiological documented infections. The most common sites of infection were
      pulmonary (49.5%), upper respiratory (16.0%), crissum (9.8%), blood stream
      (7.7%). The most common pathogens were gram-negative bacteria (44.54%), followed
      by gram-positive bacteria (37.99% ) and fungi (17.47% ). There was no significant
      difference in mortality rates between cases with febrile and cases without
      febrile (9.2% vs 4.8%, P=0.099). Multivariate analysis also suggested that >40
      years old (P=0.047, HR=5.000, 95% CI 0.853-28.013), hemodynamic instability
      (P=0.001, HR=13.185, 95% CI 2.983-54.915), prior colonization or infection by
      resistant pathogens (P=0.005, HR=28.734, 95% CI 2.921-313.744), blood stream
      infection (P=0.038, HR=9.715, 95% CI 1.110-81.969) and pulmonary infection
      (P=0.031, HR=25.905, 95% CI 1.381-507.006) were correlated with higher mortality
      rate in cases with febrile. CONCLUSIONS: Febrile was the common complication
      during neutropenia periods in patients with hematological disease. There was
      different distribution of organisms in different sites of infection. Moreove, the
      duration of neutropenia >7 days, central venous catheterization, gastrointestinal
      mucositis and previous exposure to broad-spectrum antibiotics within 90 days were
      the risk factors for the higher incidence of febrile.

PMID- 27033753
TI  - [Homoharringtonine in newly diagnosed acute promyelocytic leukemia treatment: a
      prospective, randomized controlled trial].
AB  - OBJECTIVE: To compare the efficacy and toxicities of combining homoharringtonine
      (HHT)+/-daunorubicin (DNR) with all-trans-retinoic acid (ATRA) based therapy and
      DNR plus ATRA based therapy in newly diagnosed low/intermediate risk acute
      promyelocytic leukemia (APL). METHODS: A total of 96 newly diagnosed patients
      with APL were randomized to HHT group, DNR group and HHT+ DNR group
      prospectively. The complete remission (CR) rate, the overall survival (OS) and
      event-free survival (EFS) of three groups were analyzed. RESULTS: There were 31
      patients in HHT group, 33 patients in DNR group and 32 patients in HHT+ DNR
      group. The baseline characteristics of three groups were similar. No patient died
      during induction therapy. The morphologic CR rate was 100.0%. The median time to
      peak WBC counts in HHT+DNR group (4 days, range: 1-23 days) was significantly
      shorter than that in HHT group (9 days, range: 1-27 days) (P=0.008) and DNR group
      (7 days, range: 1-27 days) (P=0.240). There was no difference among three groups
      about the incidence of differentiation syndrome, the median interval to achieve
      CR, peak WBC counts and transfusions (P >0.05). All patients achieved complete
      molecular remission (CMR) during consolidation therapy. The interval to achieve
      CMR was no significantly difference among three groups (P >0.05). The 3-year OS
      rates for HHT group, DNR group and HHT+DNR group were 95.0%, 100.0% and 91.0%,
      respectively (P=0.595). The 3-year EFS rates for three groups were 93.0%, 90.0%
      and 85.0% (P=0.382). No difference was found in the incidence of adverse events
      among three groups (P >0.05). CONCLUSIONS: Similar to DNR plus ATRA based
      therapy, HHT plus ATRA based induction and consolidation therapy should be one of
      highly-efficient treatment options for newly diagnosed APL. Clinical trial
      registration Chinese Clinical Trial Registry, ChiCTR-TRC-12002628.

PMID- 27033754
TI  - [Effects of iron chelation therapy on allogeneic hematopoietic stem cell
      transplantation in myelodysplastic syndrome patients with iron overload].
AB  - OBJECTIVE: To investigate the effects of iron chelation therapy on hematopoietic
      reconstitution and related complications of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) in patients with myelodysplastic syndrome (MDS).
      METHODS: Various clinical parameters were analyzed retrospectively in 57 MDS
      patients with iron overload who received allo-HSCT. According to the level of
      serum ferritin (SF) before transplantation divided patients into two groups: the
      effective treatment group (SF<1 000 MUg/L) and iron overload group (SF>=1 000
      MUg/L). RESULTS: 130/57 cases were received iron chelation treatment, 27/57
      patients didn' t received iron chelating therapy before transplantation. 19/30
      cases were in the effective treatment group, and the median SF level before
      transplantation was 561 (223-846) MUg/L. 11/30 cases were in the iron overload
      group, and the median SF level before transplantation was 1 262 (1 100-2 352)
      MUg/L. The median SF level was 1 540 (1 320-3 112) MUg/L of 27 patients didn't
      received iron chelating therapy before transplantation. 2 The rate of fully
      engraftment in the effective treatment group and iron overload group was 19 cases
      (100.0% ) and 34 cases (89.5% ), myeloid reconstitution of 12(10-18) and 12(11
      30) days respectively (P=0.441), and platelet reconstitution of 13(12-30) and 15
      (10-32) days respectively (P=0.579). 3The infection risk rate of the effective
      treatment group was less than iron overload group [36.8% (7/19) vs 82.4% (28/34),
      P=0.002]. 4The incidence of aGVHD in effective treatment group was less than iron
      overload group [26.3%(5/19) vs 64.7%(22/34), P= 0.010]. All patients of the
      effective treatment group were I/II degree. 16 cases were I/II degree and 6 cases
      were III/IV degree in the iron overload group. 5 6 cases of iron overload group
      accepted iron chelation treatment early post-transplantation, and SF level
      decreased from 2 870 (2 205-3 580) MUg/L to 1 270 (1 020-1 650) MUg/L. 6The
      difference of median disease-free survival time between the effective treatment
      group and iron overload group was not statistically significant [28.9 (0.3-89.5)
      months vs 21.2(0.1-81.0) months, chi(2)=3.751, P=0.053]. CONCLUSIONS: Iron
      overload obviously increased transplant-related complications, and effective iron
      chelation therapy before transplantation significantly decreased the incidence of
      infection and degree of aGVHD, thereby reduced the non-relapse mortality in
      patients with MDS.

PMID- 27033755
TI  - [Comparison of efficacy and prognostic factors in elderly acute myelogenous
      patients with MA or CAG induction chemotherapy regimen].
AB  - OBJECTIVE: To analyze the difference of efficacy and prognostic factors between
      MA and CAG induction chemotherapy in elderly acute myelogenous leukemia (AML)
      patients. METHODS: From April 2009 to September 2015, 103 consecutive
      hospitalized 60-plus-year-old AML patients were retrospectively analyzed. NPM1
      positive FLT3-ITD negative accounted for 17 cases (16.7%). Sixty-five patients
      received MA regimen and thirty-eight patients received CAG regimen. MA group had
      higher WBC and FLT3-ITD positive mutations at diagnosis compared with CAG group
      (P=0.001, P=0.005; respectively). The median follow-up was 13 months for all
      patients and 17 months for the survivors. RESULTS: Six patient (5.8%) died in
      early phase. Complete remission (CR) rate after the first cycle of induction
      chemotherapy was 51.5% (50/97). Overall CR rate was 70.1% (68/97). CR rate after
      the first cycle of induction chemotherapy and overall CR rate were indiscriminate
      between MA and CAG regimen. The time to neutrophil count recovery, the time to
      platelet count recovery and the number of platelet transfusions were
      indiscriminate between MA and CAG regimen. Among 68 CR patients, 23 patients
      relapsed at median 9 months, and cumulative incidence of relapse (CIR) at 3 years
      was (52.5+/-10.1)%. Median overall survival (OS) was 20 months. OS rate at 3
      years was 32.2%. Median disease-free survival (DFS) was 28 months. DFS rate at 3
      years was 43.7%. CIR, DFS and OS at 3 years were indiscriminate between MA and
      CAG regimen. Multivariate analysis showed that less than 70 years of age
      (P=0.001), achieved CR (P<0.001), and NPM1 (+) FLT3-ITD(-) mutation (P=0.044)
      were the independent factors for increasing OS. NPM1(+) FLT3-ITD(-) mutation was
      the independent factor for increasing DFS (P=0.042). Patients were classified by
      three prognosis factors: <70 ages, CR, and NPM1(+)FLT3-ITD(-) mutation. Patients
      with no poor prognosis factors were classified as low risk (n=13), with one
      factor as medium risk (n=52) and with two and more factors as high risk (n=31).
      There were significant differences in OS rate and DFS rate at 3 years for 3
      groups patients (60.5% vs 48.1% vs 0, P<0.001; 60.2% vs 39.4% vs 0, P=0.045;
      respectively). OS and DFS at 3 years for 3 groups' patients were indiscriminate
      between MA and CAG regimen. CONCLUSIONS: There was indiscrimination of efficacy
      among MA and CAG induction chemotherapy in old AML patients. Less than 70 years
      of age, CR and NPM1(+)FLT3-ITD(-) mutation were the independent factors for
      better survival.

PMID- 27033756
TI  - [Autologous peripheral blood hematopoietic stem cell transplantation for patients
      with primary light chain amyloidosis: experience of 31 cases in a single center].
AB  - OBJECTIVE: To evaluate the efficacy and safety of autologous peripheral blood
      hematopoietic stem cell transplantation (ASCT) for patients with primary light
      chain (AL) amyloidosis. METHODS: Clinical data, hematological and organ response,
      safety and survival status of 31 patients with AL amyloidosis who had received
      ASCT from January 2009 to June 2015 were retrospectively analyzed. RESULTS: Among
      31 patients, there were 18 males and 13 females with the median age of 55 (range,
      43-66) years old. Involvement of 1 organ was presented in 20 patients. 80.6%
      patients were defined as Mayo stage 1. The median time from diagnosis to ASCT was
      3 (range, 0.5-26) months. The median time to neutrophil and platelet engraftment
      was 11 (range, 9-12) days and 11 (range, 8-14) days, respectively. No one patient
      had transplantation related death. Among 27 evaluable patients, overall best
      hematological response was 85.2% with complete response of 63.0% and very good
      partial response of 7.4%. The median time to the best hematological response was
      4 (range, 1-21) months. 59.2% patients archived organ response and the median
      time to organ response was 8 (range, 3-18) months. After the median follow up
      time of 21 months, one patient had died and three patients had progressed.
      Therefore, the estimated 3 years progress free survival and overall survival was
      92.8% and 96.4%, respectively. CONCLUSIONS: ASCT was an effective and safe
      treatment for patients with primary AL amyloidosis in early stage.

PMID- 27033757
TI  - [Comparison of efficacy and safety of two different dose of recombinant human
      thrombopoietin regimens in severe aplastic anemia patients with immunosuppressive
      therapy].
AB  - OBJECTIVE: To compare the short-term therapeutic effect of different regimens
      combining recombinant human thrombopoietin (rhTPO) with immunosuppressive therapy
      (IST) applied in severe aplastic anemia (SAA). METHODS: The clinical data of
      newly diagnosed adult SAA patients treated with first-line IST, including 18
      patients with rhTPO daily and 43 patients with rhTPO every other day, was
      analyzed retrospectively. RESULTS: There was no significant difference between
      the basic clinical characteristics of the patients classified in different
      groups. The therapeutic effect was assessed 3 months and 6 months after IST. The
      statistical data revealed that the overall responses (OR) were not significantly
      different in daily group and every other day group (3 months: 50.0% vs 51.2%,
      P=0.934; 6 months: 77.8% vs 69.8%, P=0.525), while the good hematological
      response (CR+GPR) in SAA treated with rhTPO daily was significantly higher than
      that of patients treated with rhTPO every other day at 3 month after IST (38.9%
      vs 9.3%,P=0.011). RBC transfusion independence were not significantly different
      between the two groups after 4 weeks as well as 8 weeks treatment(4 weeks: 22.2%
      vs 18.6%,P=0.736; 8 weeks: 55.6% vs 46.5%,P=0.519), while platelet transfusion
      independence in rhTPO daily treated group was significantly higher than that in
      every other day group (88.9% vs 48.8%,P=0.003). In addition, there were no more
      adverse events observed in rhTPO daily group. CONCLUSIONS: It's more effective to
      promote hematopoietic recovery and reduce platelet transfusion dependence when
      rhTPO was daily used other than used every other day.

PMID- 27033758
TI  - [Clinical characteristics of acute myeloid leukemia with t (16;21) (p11;q22):nine
      cases report and literature review].
AB  - OBJECTIVE: To analyze the biological and clinical characteristics of acute
      myeloid leukemia (AML) with t (16;21) (p11;q22), and the curative effect and
      prognosis. METHODS: A retrospective study was conducted in nine cases with AML
      with t(16;21) (p11;q22) from January, 2009 to December, 2014 in People's Hospital
      of Peking University. RESULTS: Of 1 372 AML patients, 9 cases with t(16;21)
      (p11;q22), 4 males and 5 females, were identified. According to the FAB
      classification, 1 case was classified as M1, 5 as M2, 1 as M4, 2 as M5. Three
      patients have morphological cavity at the time of diagnosis. Immunophenotypic
      features showed the positive CD117, CD13, CD33 and CD34, especially CD56. 5 cases
      were identified as complex karyotype abnormalities, besides from t (16;21)
      (p11;q22). All cases could be detected TLS/FUS-ERG fusion genes. 9 cases acquired
      complete remission (CR) after chemotherapy. 2 cases were only treated with
      chemotherapy and relapsed after 5 months and 16 months, and died at 10 months and
      27 months after diagnosis. 7 of 9 cases accepted allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) after chemotherapy, the median survival for 21
      months (11-46 months). Summarized the 42 cases of adult AML with t (16;21)
      (p11;q22) from literature, 27 cases with chemotherapy alone, 15 cases underwent
      HSCT, the median survival for 10 (95% CI 1-17) months and 18(95% CI 2-76) months,
      respectively. The difference was statistically significant (P<0.001).
      CONCLUSIONS: AML with t (16;21) (p11;q22) was rare, it has a special form and
      distinct immunophenotypic characteristics and poor prognosis, allo-HSCT could
      improve the prognosis and should be considered after CR.

PMID- 27033759
TI  - [Clinical and genetic features of dyskeratosis congenital with bone marrow
      failure in eight patients].
AB  - OBJECTIVE: To summary clinical and genetic features of childhood dyskeratosis
      congenital (DC) patients with bone marrow failure. METHODS: The clinical data of
      8 DC patients with bone marrow failure diagnosed between September 2010 and
      September 2015 were collected. Whole exons with flanking regions of the 16
      telomere-related genes, including DKC1, TERC, TERT, NOP10, NHP2, TINF2 and so on,
      were analyzed by next generation sequence. RESULTS: Six males and two females
      were included, with a median age of 42(15-60) months. The median blood cell count
      at onset were as follow: WBC 3.99 (1.26-5.44) * 10(9)/L, ANC 1.11 (0.38-2.15) *
      10(9)/L, RBC 2.45 (0.37-3.56) * 10(12)/L, HGB 82.5(15-127) g/L, PLT 27 (2-112)
      *10(9)/L. Hypoplastic or marked hypoplastic bone marrow were seen in 6 patients.
      DKC1 mutiaton were indentified in 3 patients: one c.961C>A mutation, and two
      c.1058C>T mutation. TINF2 mutations were identified in 4 patients: c.849delC,
      c.844C>T, c.811C>T, c.862T>A combined c.871delA. One patient had TINF2 mutation
      c.848C>A combined TERT mutation c.1138C>T. DKC1 c.961C>A mutation, TINF2
      c.849delC mutation and TINF2 c.871delA mutaion were not reported so far. 5 of 7
      patients got better after androgen administration. During follow-up, one patient
      died of serious infection, the other seven patients continued the treatment.
      CONCLUSIONS: TINF2 and DKC1 mutations were the main genetic phenotypes in
      childhood DC with marrow failure patients. Androgen is effetive in some cases.

PMID- 27033760
TI  - [Clinical characteristics and prognosis of 35 patients with therapy-related
      hematological neoplasms].
AB  - OBJECTIVE: To investigate the morbidity, treatment outcomes and prognosis of 35
      therapy-related hematological neoplasms patients. METHODS: A total of 35 cases of
      therapy-related hematological neoplasms were examined genetically and
      immunologically using flow cytometry, karyotype analysis and FISH, and their
      clinical data were retrospective analyzed and literatures were reviewed. RESULTS:
      Among 35 patients, there were 20 cases of therapy-related acute myeloid leukemia
      (t-AML), 4 cases of therapy-related acute lymphoblastic leukemia (t-ALL), 1 case
      of acute mixed leukemia, therapy-related non-hodgkin' s lymphoma (t-NHL) in 8
      cases and myelodysplastic syndrome (t-MDS) in 2 cases. The median onset of t-HN
      was 29(16-90) months, the median OS of t-HN was 14(1-60) months, and 3 years of
      OS was 17.1%. Among therapy-related acute leukemia (t-AL) patients, 40% (10/25)
      patients had combined complex karyotype, 36% (9/25) patients with MLL gene
      rearrangement, 12% (3/25) patients with combined AML/ETO fusion gene, 1 case with
      NPM1 point mutation and 1 case with P16 gene deletion. CONCLUSIONS: Therapy
      related hematological neoplasms had a worse prognosis.

PMID- 27033761
TI  - [Expression of porforin and granzyme B in familial hemophagocytic
      lymphohistiocytosis].
AB  - OBJECTIVE: To analyze the correlation between genetic variants of PRF1 and
      expression level of perforin and granzyme B protein, and further determine the
      relationship between PRF1 gene variants and cytotoxic T lymphocyte/natural killer
      (CTL/NK) cell function in famililal hemophagocytic lymphohistiocytosis (FHL2).
      METHODS: Eight children of FHL2 (P1-P8) after treatment, as well as parents and
      siblings of P1-P5 were included, and thirty healthy children came for physical
      examination were designated as controls. PRF1, Unc13D, STX11, STXBP2, RAB27A,
      LYST, SH2D1A, BIRC4 exons were amplified by PCR and followed by direct
      sequencing. Bioinformatics analysis of mutant PRF1 was performed by ExPASy online
      system. Perforin and granzyme B expression on cytotoxic lymphocyte was detected
      by flow cytometry. RESULTS: 1 Three of eight FHL2 children harbored heterozygous
      missense of PRF1 exons: P1 had compound heterozygous missense mutations (R4C and
      R33H) and P2 had heterozygous mutations (V50L), P3 had heterozygous mutations
      (R489W), which confirmed the diagnosis of FHL2. The father (F1) and younger
      brother (B1) of P1 also had compound heterozygous missense mutation (R4C/R33H),
      the mother (M2) and younger brother (B2) of P2 had V50L mutation, the father (F3)
      of P3 had no R489W mutation and the mother of P3 did not participate in this
      research, so mutation of R4C/R33H of P1 inherited from paternal line, and V50L
      mutation of P2 came from maternal line, R489W mutation of P3 came from maternal
      line. 2 Comparing to control group, perforin expression of CD8(+) T cells and
      natural killer (NK) cells of P1, F1, B1, P2, M2 and B2 decreased significantly,
      but there was no significant difference between two groups in terms of granzyme B
      expression. CONCLUSIONS: R4C/R33H compound heterozygous mutation and V50L
      heterozygous mutation all cause lower expression of perforin on CTL/NK cells, and
      may be causative mutations for familial hemophagocytic lymphohistiocytosis.

PMID- 27033762
TI  - [Clinical profile of autoimmune hemolytic anemia with monoclonal gammopathy
      IgMkappa].
AB  - OBJECTIVE: To explore the clinical features of autoimmune hemolytic anemia (AIHA)
      with monoclonal gammopathy IgMkappa. METHODS: The clinical and laboratory
      features of 12 AIHA with monoclonal gammopathy IgMkappa were retrospectively
      analyzed. RESULTS: 12 cases with monoclonal immunoglobulin IgMkappa were found in
      85 patients with AIHA by immune-fixation electrophoresis from June 2012 to June
      2014. There were 4 (5.7% ) cases of warm AIHA and 8 (80.0% ) cases of cold
      agglutinin syndrome (CAS). The 4 warm AIHA were primary type, and 4 CAS cases
      were secondary to lymphoproliferative disorder (small-cell lymphocytic lymphoma)
      and the other 4 CAS were primary type. Positive TCR gene rearrangements were
      detected in 2 warm AIHA patients; IgH rearrangements positive were detected in 6
      CAS patients, and TCR/IgH rearrangements positive were seen in 1 CAS patient.
      Four warm AIHA cases received glucocorticoid treatment, three cases of complete
      remission, one case of partial response. Three CAS cases were treated with low
      dose of rituximab, two cases of partial response and one case of invalid. Two CAS
      patients received chemotherapy of COP regimen, one case of partial response and
      one case of invalid. Two CAS patients of normal hemoglobin were suggested to keep
      warm, and one case died of infection after splenectomy. CONCLUSIONS: Mostly, CAS
      patients had monoclonal immunoglobulin IgMkappa, but warm AIHA patients with
      monoclonal IgM were fewer.

PMID- 27033763
TI  - [Acute myeloid leukemia complicated with complex karyotypes and T-lymphoblastic
      lymphoma: a case report].

PMID- 27033764
TI  - [Study on the expression of T, B lymphocyte antigen and platelet antibodies in
      patients with platelet transfusion refractoriness].
AB  - OBJECTIVE: To explore whether T lymphocytes subgroup, B lymphocytes, platelet
      antigen CD41a, CD61 or platelet antibodies are involved in the platelet
      transfusion refractoriness. METHODS: Forty-seven patients diagnosed as platelet
      transfusion refractoriness and 32 patients that achieved effective platelet
      therapy were ennolled in this study. Flow cytometry was performed to detect the
      proportion of cytotoxic T cell (CD3(+)CD4(-)CD8(+)), helper T cell
      (CD3(+)CD4(+)CD8(-)) and B lymphocytes (CD19 (+) ), and the expression of
      platelet glycoproteins, including CD41a and CD61, while platelet antibodies were
      also measured by solid-phase agglutination. RESULTS: The significant lower level
      of helper T cell (36.60% vs 48.53%), higher level of cytotoxic T cell (53.26% vs
      44.02%) and lower cytotoxic/helper T cell ratio (0.85 vs 1.31) were observed in
      platelet refractoriness group when compared with effective platelet therapy group
      (P<0.05). However, the significant difference was not observed in B lymphocytes
      between the two group (3.02% vs 2.85%, P>0.05). Platelet glycoproteins CD41a and
      CD61 and antibodies were both expressed at high levels in platelet refractoriness
      group (88.10% vs 51.69%, 88.36% vs 51.83%, 85.37% vs 14.82%, respectively,
      P<0.05). CONCLUSIONS: Activation of cytotoxic T cells, suppression of helper T
      cells, higher expression level of platelet glycoproteins CD41a and CD61 as well
      as the development of anti-platelet antibodies are involved in the immunologic
      mechanism of platelet refractoriness.

PMID- 27033765
TI  - [High-dose pemetrexed in combination with temolozomide for the treatment of newly
      diagnosed primary central nervous system lymphoma].

PMID- 27033766
TI  - [Clinical analysis of thromboembolism associated with lenalidomide-based regimens
      for multiple myeloma patients].

PMID- 27033767
TI  - [Study of the effect of natural killer cells kill dendritic cells by blockade of
      CD158 receptor epitipe].

PMID- 27033768
TI  - [Mott cells in multiple myeloma: a case report and literature review].

PMID- 27033769
TI  - [MRI feature of the primary spinal lymphoma].

PMID- 27033770
TI  - [Angioimmunoblastic T-cell lymphoma-induced linitis plastica and literatures
      review].

PMID- 27033771
TI  - [Role of extracellular vesicles in hematological malignancies].

PMID- 27033772
TI  - [Advances on immunomodulatory drugs against multiple myeloma].

PMID- 27033773
TI  - Universal real-time PCR assay for quantitation and size evaluation of residual
      cell DNA in human viral vaccines.
AB  - Residual host cellular DNA (rcDNA) is one of the principal risk associated with
      continuous cell lines derived medicines such as viral vaccines. To assess rcDNA
      degradation, we suggest two quantitative real-time PCR assays designed to
      separately quantify target sequences shorter and longer than the 200 bp risk
      limit, the relative abundance of both targets reflecting the extent of rcDNA
      fragmentation. The conserved multicopy ribosomal 18S RNA gene was targeted to
      detect host cell templates from most mammalian cell substrates commonly used in
      the manufacture of human viral vaccines. The detection range of the method was
      assessed on purified DNA templates from different animal origins. The standard
      calibrator origin and structural conformation were shown crucial to achieve
      accurate quantification. Artificial mixtures of PCR products shorter and longer
      than 200 bp were used as a model to check the ability of the assay to estimate
      the fragment size distribution. The method was successfully applied to a panel of
      Vero cell derived vaccines and could be used as a universal method for
      determination of both content and size distribution of rcDNA in vaccines. 

PMID- 27033774
TI  - The formation mechanism for printed silver-contacts for silicon solar cells.
AB  - Screen-printing provides an economically attractive means for making Ag
      electrical contacts to Si solar cells, but the use of Ag substantiates a
      significant manufacturing cost, and the glass frit used in the paste to enable
      contact formation contains Pb. To achieve optimal electrical performance and to
      develop pastes with alternative, abundant and non-toxic materials, a better
      understanding the contact formation process during firing is required. Here, we
      use in situ X-ray diffraction during firing to reveal the reaction sequence. The
      findings suggest that between 500 and 650  degrees C PbO in the frit etches the
      SiNx antireflective-coating on the solar cell, exposing the Si surface. Then,
      above 650  degrees C, Ag(+) dissolves into the molten glass frit - key for
      enabling deposition of metallic Ag on the emitter surface and precipitation of Ag
      nanocrystals within the glass. Ultimately, this work clarifies contact formation
      mechanisms and suggests approaches for development of inexpensive, nontoxic solar
      cell contacting pastes. 

PMID- 27033775
TI  - On-site analysis of acetylcholinesterase and butyrylcholinesterase activity with
      the ChE check mobile test kit-Determination of reference values and their
      relevance for diagnosis of exposure to organophosphorus compounds.
AB  - Poisoning by organophosphorus compounds (OP) still poses a major medical
      challenge. Diagnosis of clinical signs of OP poisoning is still the most
      important parameter for the initiation of specific treatment. However, in case of
      unspecific signs and of delayed onset of cholinergic crisis a rapid, reliable and
      on-site analysis of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
      activity would be of great value. Recently the ChE check mobile, a CE-certified
      ready to use kit for the determination of whole blood AChE and BChE activities,
      was developed. Here, we evaluated whole blood AChE and BChE reference values with
      samples taken from 181 male and 61 female volunteers and analyzed them on-site
      with the ChE check mobile test kit. The analysis of the data revealed a large
      inter-individual variability (BChE>AChE), only a small sex difference for AChE
      but a significant difference for BChE activities. The now available normal range
      values enable an evaluation of determined AChE and BChE activities in case of
      suspected exposure to OP nerve agents and pesticides. However, the large inter
      individual variability of AChE and BChE activities calls for the determination of
      pre-exposure values in specific subpopulations in order to enable the diagnosis
      of low-level OP exposure. 

PMID- 27033776
TI  - Drugs and driving in China: Status and challenge.

PMID- 27033777
TI  - Research and Evaluations of the Health Aspects of Disasters, Part IX: Risk
      Reduction Framework.
AB  - A disaster is a failure of resilience to an event. Mitigating the risks that a
      hazard will progress into a destructive event, or increasing the resilience of a
      society-at-risk, requires careful analysis, planning, and execution. The Disaster
      Logic Model (DLM) is used to define the value (effects, costs, and outcome(s)),
      impacts, and benefits of interventions directed at risk reduction. A Risk
      Reduction Framework, based on the DLM, details the processes involved in hazard
      mitigation and/or capacity-building interventions to augment the resilience of a
      community or to decrease the risk that a secondary event will develop. This
      Framework provides the structure to systematically undertake and evaluate risk
      reduction interventions. It applies to all interventions aimed at hazard
      mitigation and/or increasing the absorbing, buffering, or response capacities of
      a community-at-risk for a primary or secondary event that could result in a
      disaster. The Framework utilizes the structure provided by the DLM and consists
      of 14 steps: (1) hazards and risks identification; (2) historical perspectives
      and predictions; (3) selection of hazard(s) to address; (4) selection of
      appropriate indicators; (5) identification of current resilience standards and
      benchmarks; (6) assessment of the current resilience status; (7) identification
      of resilience needs; (8) strategic planning; (9) selection of an appropriate
      intervention; (10) operational planning; (11) implementation; (12) assessments of
      outputs; (13) synthesis; and (14) feedback. Each of these steps is a
      transformation process that is described in detail. Emphasis is placed on the
      role of Coordination and Control during planning, implementation of risk
      reduction/capacity building interventions, and evaluation. Birnbaum ML , Daily EK
      , O'Rourke AP , Loretti A . Research and evaluations of the health aspects of
      disasters, part IX: Risk-Reduction Framework. Prehosp Disaster Med.
      2016;31(3):309-325. 

PMID- 27033778
TI  - The impact of transrectal prostate biopsy on erectile function.
AB  - OBJECTIVE: To assess erectile function at different periods of time in patients
      who undergo transrectal prostate biopsy (TRPB). MATERIAL AND METHODS: A total of
      364 patients underwent TRPB. All of the patients were assessed using the
      International Index of Erectile Function-5 (IIEF-5). All patients with a positive
      result for cancer or with previous erectile dysfunction in the initial assessment
      were excluded. Ninety-three patients were included and were assessed before the
      biopsy and at 4, 12 and 24 weeks after the TRPB, using the IIEF-5 and assessing
      erectile function across these time periods. RESULTS: We assessed 93 patients.
      During the first prebiopsy assessment, 100% of the patients scored >=22 points.
      In the first postbiopsy evaluation at 4 weeks, 66.6% scored >= 22 points, and
      33.3% had erectile dysfunction, thereby indicating a statistically significant
      reduction in the IIEF-5 score (P=.001). In the second postbiopsy evaluation, only
      9.1% patients still had mild to moderate erectile dysfunction (P=.04). By the
      end, 92.48% of the patients scored >= 22 points, and 7.52% still had mild
      erectile dysfunction, without presenting a significant difference (P=.1).
      CONCLUSIONS: After a TRPB, the drop in IIEF-5 scores and the presence of erectile
      dysfunction are temporary and transient, with greater impairment during the first
      month following the procedure and improvement starting after the first month,
      with almost total recovery at 6 months.

PMID- 27033779
TI  - Comment to "Laparoscopic access overview: Is there a safest entry method?".

PMID- 27033780
TI  - How completely are physiotherapy interventions described in reports of randomised
      trials?
AB  - BACKGROUND: Incomplete descriptions of interventions are a common problem in
      reports of randomised controlled trials. To date no study has evaluated the
      completeness of the descriptions of physiotherapy interventions. OBJECTIVES: To
      evaluate the completeness of the descriptions of physiotherapy interventions in a
      random sample of reports of randomised controlled trials (RCTs). DATA SOURCES: A
      random sample of 200 reports of RCTs from the PEDro database. STUDY SELECTION OR
      ELIGIBILITY CRITERIA: We included full text papers, written in English, and
      reporting trials with two arms. We included trials evaluating any type of
      physiotherapy interventions and subdisciplines. DATA EXTRACTION AND DATA
      SYNTHESIS: The methodological quality was evaluated using the PEDro scale and
      completeness of intervention description using the Template for Intervention
      Description and Replication (TIDieR) checklist. The proportion and 95% confidence
      interval were calculated for intervention and control groups, and used to present
      the relationship between completeness and methodological quality, and
      subdisciplines. RESULTS: Completeness of intervention reporting in physiotherapy
      RCTs was poor. For intervention groups, 46 (23%) trials did not describe at least
      half of the items. Reporting was worse for control groups, 149 (75%) trials
      described less than half of the items. There was no clear difference in the
      completeness across subdisciplines or methodological quality. LIMITATIONS: Our
      sample were restricted to trials published in English in 2013. CONCLUSION AND
      IMPLICATIONS OF KEY FINDINGS: Descriptions of interventions in physiotherapy RCTs
      are typically incomplete. Authors and journals should aim for more complete
      descriptions of interventions in physiotherapy trials.

PMID- 27033782
TI  - Identifying barriers and facilitators to participation in pressure ulcer
      prevention in allied healthcare professionals: a mixed methods evaluation.
AB  - OBJECTIVES: To evaluate the barriers and facilitators for allied health
      professional's participation in pressure ulcer prevention. DESIGN: Mixed method
      cohort study. SETTING: Single centre study in an acute university hospital trust.
      PARTICIPANTS: Five physiotherapists and four occupational therapists were
      recruited from the hospital trust. Therapists had been working in the National
      Health Service (NHS) for a minimum of one year. MAIN OUTCOME MEASURES: Therapist
      views and experiences were collated using an audio recorded focus group. This
      recording was analysed using constant comparison analysis. Secondary outcomes
      included assessment of attitudes and knowledge of pressure ulcer prevention using
      questionnaires. RESULTS: Key themes surrounding barriers to participation in
      pressure ulcer prevention included resources (staffing and equipment), education
      and professional boundaries. Fewer facilitators were described, with new training
      opportunities and communication being highlighted. Results from the
      questionnaires showed the therapists had a positive attitude towards pressure
      ulcer prevention with a median score of 81% (range 50 to 83%). However, there
      were gaps in knowledge with a median score of 69% (range 50 to 77%). CONCLUSIONS:
      The therapist reported several barriers to pressure ulcer prevention and few
      facilitators. The primary barriers were resources, equipment and education.
      Attitudes and knowledge in AHPs were comparable to data previously reported from
      experienced nursing staff.

PMID- 27033781
TI  - Feasibility of a physical activity pathway for Irish primary care physiotherapy
      services.
AB  - OBJECTIVES: To establish consensus on a physical activity pathway suitable for
      use by physiotherapists in Irish primary care. The physical activity pathway
      "Let's Get Moving" was examined to agree recruitment criteria and seek consensus
      on component parts. DESIGN: Modified Delphi approach which attempts to achieve a
      convergence of opinion, over a series of iterations. Three rounds of
      questionnaires were used. SETTING: Primary care. PARTICIPANTS: 41 senior
      physiotherapists working in primary care for a median of 6 years (IQR 3.7 to
      8.5). MAIN OUTCOME MEASURES: Statements achieving consensus; defined as at least
      70% of participants scoring a 6 or a 7, indicating high agreement, on a 7 point
      Likert scale. RESULTS: The response rate was 98%. There was a high degree of
      consensus for many components of the pathway. Participants agreed that all
      patients attending physiotherapy should be eligible for recruitment onto the
      pathway as well as accepting referrals from other health professionals and direct
      access from the public. Private physiotherapists highlighted concerns about
      recruiting fee paying patients onto the pathway. The pathway should be integrated
      into other preventative and chronic disease programmes in primary care.
      Modifications to the original pathway included the use of a pedometer in addition
      to the General Practice Physical Activity Questionnaire. Training needs in
      physical activity screening and motivational interviewing, as well as additional
      staffing were identified to support implementation. CONCLUSIONS: The Physical
      Activity Pathway "Let's Get Moving" was accepted as a clinically feasible
      resource to primary care physiotherapists with some modifications and with the
      support of additional resources.

PMID- 27033783
TI  - Patient reported outcome measures (PROMs) for goalsetting and outcome measurement
      in primary care physiotherapy, an explorative field study.
AB  - OBJECTIVES: Routine use of patient reported outcome measures (PROMs) may provide
      an effective way of monitoring patient valued outcomes. In this study we explored
      (1) the current use of PROMs; (2) to what extent the goals correspond with the
      selected PROMs; (3) the health outcomes based on PROMs. DESIGN: Observational
      clinical cohort study. SETTING: Dutch primary care physiotherapy practices
      (n=43). PARTICIPANTS: Patients (n=299) with neck pain or low back pain. MAIN
      OUTCOME MEASURES: The number of PROMs used per patient were calculated. The
      International Classification of Functioning, Disability and Health was used to
      map the patients' goals and the percentages of PROMS selected that match the
      domains of the goals were calculated. Health outcomes were assessed using two
      approaches for estimating the minimal clinically important difference (MCID).
      RESULTS: Repeated measurements with the Visual Analogue Scale, the Patient
      Specific Complaints questionnaire, the Quebec Back Pain Disability Scale, or the
      Neck Disability Index were completed by more than 60% of the patients. The PROMs
      used matched in 46% of the cases with goals for pain improvement, and in 43% with
      goals set at activity/participation level. The mean differences between baseline
      and follow up scores for all PROMs were statistically significant. Improvements
      of patients based on MCID varied from 57% to 90%. CONCLUSIONS: PROMs were used in
      the majority of the patients, showed improved health outcomes and fitted
      moderately with goals. The results of this study can be used for future research
      assessing the routine use of outcome measurements with PROMs.

PMID- 27033784
TI  - [Immunoregulative effect of Fasudil on encephalomyelitic T cells in experimental
      autoimmune encephalomyelitis mice].
AB  - OBJECTIVE: To explore the therapeutic effect of Fasudil-modified splenic
      mononuclear cells (MNCs) in experimental autoimmune encephalomyelitis (EAE) and
      the possible mechanisms.? METHODS: C57BL/6 female mice were immunized with myelin
      oligodendrocyte glycoprotein peptide 35-55 to establish active immunity EAE
      model. Splenic MNCs were isolated on the 9th day after immunization and treated
      with or without Fasudil for 72 h in vitro. These cells were collected for
      analysis of the variance of T cell subtypes, the level of cytokines and the
      activity of Rho kinase (ROCK). MNCs (5*107 cells) were resuspended in 500 uL of
      phosphate buffer solution (PBS) and transferred into EAE model (intraperitoneal
      injection), which was divided into a PBS-MNCs group and a Fasudil-MNCs group.
      Changes of body weight and clinical symptom scores were observed.? RESULTS:
      Splenic encephalitogenic MNCs from EAE mice on the 9th day after immunization
      could establish passive transfer EAE model. But Fasudil-treated MNCs did not
      trigger EAE development. Compared with the PBS-MNCs group, the loss of body
      weight was less in the Fasudil-MNCs group. The in vitro experiment indicated that
      Fasudil could suppress the activity of ROCK on MNCs (P<0.01), decrease the
      percentage of CD4+ T cells with the expression of interferon-gamma (IFN-gamma)
      and interleukin-17 (IL-17) (IFN-gamma: P<0.01; IL-17: P<0.05), while increase the
      secretion of CD4+ T cells with the expression of transforming growth factor-beta
      (TGF-beta) and IL-10 (all P<0.001) . Furthermore, Fasudil could inhibit the
      release of IL-17 (P<0.001) and enhance the level of IL-10 (P<0.05).? CONCLUSION:
      Fasudil-modified cell therapy affects the occurrence and development of EAE by
      inhibiting the inflammatory reaction of helper T cell 1 (Th1) and Th17 while
      enhancing the immunoregulative effect of Th2.

PMID- 27033785
TI  - [Effect of polymorphisms of NF-kappaB and PXR on platinum-based chemotherapy for
      non-small cell lung cancer].
AB  - OBJECTIVE: To investigate the effect of polymorphisms of NF-kappaB rs230521, NF
      kappaB rs4648068 and pregnane X receptor (PXR) rs3814058 on platinum-based
      chemotherapy for non-small cell lung cancer patients. ? METHODS: We collected 262
      cases of non-small cell lung cancer patients, and then analyzed the genotypes of
      NF-kappaB and PXR by MassARRAY method. The impact of polymorphisms on efficacy,
      gastrointestinal toxicity and hematological toxicity was analyzed by logistic
      regression.? RESULTS: Compared to patients with GG genotype, patients with NF
      kappaB rs230521 CC genotype had the higher risk to suffer hematological toxicity
      (OR=3.485, P=0.011). Patients with PXR rs3814058 CC and CT genotype exhibited
      higher possibility to suffer hematological toxicity than those with TT (OR=2.045,
      P=0.048). Polymorphism of NF-kappaB rs4648068 did not show significant effect on
      chemotherapy efficacy and occurrence of gastrointestinal toxicity and
      hematological toxicity.? CONCLUSION: Patients with NF-kappaB rs230521 CC, PXR
      rs3814058 CC and CT had higher risk to suffer hematological toxicity during
      platinum-based chemotherapy for non-small cell lung cancer. A rational dosage and
      course of treatment should be chosen to protect the patients with high risk
      genotype suffering hematological toxicity during their platinum-based therapy.

PMID- 27033786
TI  - [Expression of miR-21 in peripheral blood serum and mononuclear cells in patients
      with chronic obstructive pulmonary disease and its clinical significance].
AB  - OBJECTIVE: To explore expression of miR-21 in peripheral blood serum and
      mononuclear cells of patients with chronic obstructive pulmonary disease (COPD),
      and to discuss the significance and underlying mechanisms.? METHODS: The subjects
      were divided into a healthy control group (n=41) and a COPD group (n=49). The miR
      21 level was detected by quantitative real-time PCR. The correlations between miR
      21 and lung function or forced expiratory volume in one second (FEV1) were
      analyzed.? RESULTS: The expression levels of miR-21 in the serum and mononuclear
      cells in the COPD group were significantly elevated compared with those in the
      healthy group (P<0.05). The expression of miR-21 was correlated with the lung
      function of COPD patients. The expression level of miR-21 in the COPD patients
      was positively correlated with FEV1. ? CONCLUSION: The upregulation of miR-21 in
      peripheral blood serum and mononuclear cells of COPD patients may contribute to
      the pathogenesis of COPD and the severity of this disease.

PMID- 27033787
TI  - [Effects of aconitine poisoning and Shuang-huang-lian treatment on the expression
      of myocardial ?ryanodine receptor].
AB  - OBJECTIVE: To study the impact of aconitine and Shuang-huang-lian injection on
      the expression of myocardial ryanodine receptor (RyR2) and to discuss the anti
      arrhythmic mechanisms of Shuanghuanglian against aconitine poisoning.? METHODS: A
      total of 52 SD rats were randomly divided into 3 groups: aconitine group (group
      A, n=20), Shuang-huang-lian group (group B, n=20) and control group (group C,
      n=12). Aconitine at a dose of 0.3 mg/kg was firstly administrated to the rats of
      group A and group B through gavage. 30 minutes later, normal saline was delivered
      to rats in group A through intraperitoneal injection, while rats in group B
      received Shuang-huang-lian at a dose of 100 mg/kg through intraperitoneal
      injection. Group C accepted twice administration of normal saline by gavage and
      intraperitoneal injection. The disposals for each group were implemented for 10
      consecutive days. The rats' electrocardiograms (ECG) were recorded on day 1, 3, 6
      and 10. Immunofluorescent staining technique and real-time quantitative PCR
      technique was used to detect the protein and mRNA expression of myocardial RyR2.?
      RESULTS: The arrhythmia scores of group B at different time were lower than group
      A and the difference was statistically significant (P<0.05 or P<0.01). The
      protein and mRNA expression of RyR2 in group A was slightly increased on the
      first day compared to group B and group C, with no statistical significance
      (P>0.05). On day 3, 6 and 10, the expression of RyR2 protein and mRNA in group A
      was dramatically increased compared to group B and group C (P<0.01). ?
      CONCLUSION: Shuang-huang-lian injection can effectively prevent the arrhythmia
      caused by aconitine, which is related to suppressing the aconitine-induced RyR2
      expression.

PMID- 27033788
TI  - [Mechanism of inhibitory effects of silencing high mobility group box-1 on
      invasion and migration of ?endometrial carcinoma of uterus].
AB  - OBJECTIVE: To determine the effects of p38 mitogen-activated protein kinase
      (MAPK) signal pathway after small hairpin RNA on inhibiting the expression of
      high mobility group box-1 (HMGB1), and to explore the mechanism responsible for
      the effects of HMGB1 on invasion and migration of endometrial carcinoma of
      uterus.? METHODS: Based on RNA interference technology, we designed and
      synthetized HMGB1 small hairpin RNA (HMGB1 shRNA-1, HMGB1 shRNA-2, HMGB1 shRNA-3,
      HMGB1 shRNA-1), and then transfected HMGB1 shRNA plasmids into HEC-1A cells. The
      expression of genes and proteins was examined by RT-PCR and Western blot. The
      activity of HEC-1A cells was evaluated by the methyl thiazolyl tetrazolium (MTT)
      method.? RESULTS: HMGB1 shRNA effectively inhibited the expression of the HMGB1
      and p38MAPK in HEC-1A cells (P<0.05). Among the shRNAs, the inhibitory effect of
      HMGB1 shRNA-3 was the best (P<0.05). According to the results of MTT, the growth
      of HEC-1A cells was obviously inhibited after transfection of HEC-1A HMGB1 shRNA
      (P<0.05). ? CONCLUSION: Downregulation of HMGB1 may effectively inhibit
      proliferation, invasion and migration of HEC-1A cells in endometrial carcinoma of
      uterus, which is dependent on p38MAPK signal pathway.

PMID- 27033789
TI  - [Expression of epithelial cell adhesion molecule and molecular subtypes and
      prognosis of breast cancer].
AB  - OBJECTIVE: To investigate clinicopathological and prognostic significance of
      epithelial cell adhesion molecule (EpCAM) expression in breast cancer and its
      molecular subtypes.? METHODS: The expression of EpCAM in 835 patients with breast
      invasive ductal carcinoma was detected by immunohistochemical Max VisionTM
      method, and its correlation with clinical pathological features and prognosis was
      analyzed.? RESULTS: The positive expression of EpCAM was related to histological
      grade, lymph node metastasis, tumor size, clinical stage, the expression of
      estrogen receptor (ER), progesterone receptor (PR) and HER2 (P<0.05). The
      positive expression rates of EpCAM were 19.2%, 73%, 48.9%, 72.2%, and 62.1%, in
      Luminal A, Luminal B (HER2-), Luminal B(HER2+), HER2+, and triple-negative
      subtype, respectively. Log-rank test and univariate COX analysis showed that the
      EpCAM expression was associated with a poor prognosis in all patients (P<0.001),
      as well as the triple-negative subtype, luminal B subtype (HER2-), and HER2+
      subtype (P<0.05). Multivariate COX analysis showed that EpCAM expression was
      associated with the survival in patients with the triple-negative or HER2+
      subtype (P<0.05).? CONCLUSION: EpCAM may be associated with progress of breast
      cancer. It is an independent prognostic factor in breast cancer, especially in
      the triple-negative and HER2+ subtypes.

PMID- 27033790
TI  - [Mechanisms for inhibitory effect of ALDH2 on doxorubicin-induced cytotoxicity in
      C2C12 myogenic cell line].
AB  - OBJECTIVE: To investigate the mechanisms for inhibitory effect of aldehyde
      dehydrogenase 2 (ALDH2) on doxorubicin (DOX)-induced cytotoxicity in C2C12
      myogenic cell line.? METHODS: Cell apoptosis was evaluated by flow cytometry and
      the activity of capase-3/7. The relative content of reactive oxygen species (ROS)
      and 4-hydroxynonenal (4-HNE) were detected by chemical fluorometric enzyme
      immunoassay. The protein and mRNA expression of ALDH2, Bcl-2, NADPH oxidase 2
      (NOX2) and the cytoplasmic subunit p-p47PHOX were evaluated by Western blot and
      quantitative PCR, respectively. ? RESULTS: Overexpression of ALDH2 attenuated DOX
      induced cell toxicity (increase in apoptosis and inhibition of proliferation),
      which were reversed by downregulation of ALDH2. Overexpression of ALDH2 reduced
      p47PHOX phosphorylation levels, and suppressed activation of NOX2 and ROS
      production, which were reversed by downregulation of ALDH2. Moreover, apocynin,
      an inhibitor of NOX, reduced the cytotoxicity of DOX concomitantly with a
      decrease in phosphorylation of p47PHOX, ROS production and caspase-3/7 activity,
      and an increase in the activity and expression of ALDH2. ? CONCLUSION: DOX
      induced cytotoxicity is related to increase of intracellular oxidative stress,
      which is involved in unregulation of NOX2 and downregulation of ALDH2. Activation
      of ALDH2 could exert cytoprotection via inhibiting NOX2-dependent ROS production.

PMID- 27033791
TI  - [Interaction between polymorphisms of TLR4 gene ?G11367C in 3' untranslated
      region and IkappaB-alpha Hae III in ?acute pancreatitis and the degree of
      severity].
AB  - OBJECTIVE: To investigate the interaction between polymorphism of Toll-like
      receptor 4 (TLR4) gene G11367C in 3' untranslated region (UTR) and inhibitor of
      nuclear factor kappaB (IkappaB)-alpha ?Hae III in acute pancreatitis (AP) and the
      degree of severity.? METHODS: A total of 450 patients with confirmed AP (AP
      group), who came from the First Affiliated Hospital of Xinxiang Medical College
      from May 2013 to June 2015, were divided into a mild AP subgroup (MAP subgroup),
      a moderately severe AP (MSAP subgroup), and a severe acute AP (SAP subgroup)
      (n=150 in each group). One hundred fifty healthy persons were served as a control
      group. There was no significant difference in age, gender, ethnicity and
      birthplace among all groups. The genetic polymorphisms of TLR4 gene G11367C in 3'
      untranslated region and IkappaB-alpha Hae III were analyzed by polymerase chain
      reaction (PCR). Eligible participants were personally interviewed by a
      questionnaire. Unconditional logistic regression model and single factor analysis
      were performed to calculate the adjusted odds ratios (OR) and 95% confidence
      intervals (95% CI) of G11367C and IkappaB-alpha Hae III polymorphisms,
      respectively. The interaction of nucleotide polymorphisms was analyzed.? RESULTS:
      The frequencies of G11367C (GC), IkappaB-alpha Hae III (AG) and IkappaB-alpha Hae
      III (GG) were 69.56%, 33.78% and 36.22% in the AP group; 49.33%, 24.67% and
      26.00% in the MAP subgroup; 70.67%, 34.67% and 36.67% in the MSAP subgroup;
      88.67%, 42.00% and 46.00% in the SAP subgroup and 26.67%, 14.00% and 14.67% in
      the control group, respectively. There was significant difference in the
      frequencies betweenc the AP group and the control group, or among each AP
      subgroup (all P<0.01). The risk of AP was significantly increased in the subjects
      with G11367C (GC) genotype (ORAP=6.2828, ORMAP=2.6776, ORMSAP=6.6250,
      ORSAP=21.5147), which was also increased in those with IkappaB-alpha Hae III (AG)
      genotype (ORAP=5.7369, ORMAP=2.5277, ORMSAP=6.1824, ORSAP=17.8572) and in those
      with IkappaB-alpha Hae III (GG) genotype (ORAP=5.8724, ORMAP=2.5902,
      ORMSAP=6.4027, ORSAP=18.9022). The combined analysis of the polymorphisms showed
      that the percentage of G11367C (GC)/ IkappaB-alpha Hae III (GG) in the AP group,
      the MAP subgroup, the MSAP subgroup, the SAP subgroup and the control groups was
      26.44%, 12.67%, 26.00%, 40.67% and 4.00%, respectively, with significant
      difference in the frequency among all groups (all P<0.01). The people who carried
      with Pro12Ala (AA)/Pro198Leu (LL) had a high risk of AP (ORAP=30.1314,
      ORMAP=6.7612, ORMSAP=39.5000, ORSAP=401.5833), and the statistical analysis
      suggested a positive interaction between Pro12Ala (AA) and Pro198Leu (LL) in
      increasing the risk of AP (All gamma>1). Similarly, there were also positive
      interactions in the pathogenesis of AP between G11367C (GC) and IkappaB-alpha Hae
      III (AG) (All gamma>1). ? CONCLUSION: These carriers of G11367C(GC), IkappaB
      alpha Hae III(AG) and IkappaB-alpha Hae III (GG) genotypes may have a high risk
      of AP occurency, and there are significant interactions between genetic
      polymorphisms of G11367C and IkappaB-alpha Hae III, which increaes the risk of
      the occurrence and development of AP.

PMID- 27033792
TI  - [Application of endoscopic full-thickness resection in the treatment of gastric
      tumors originated from?the muscularis propria].
AB  - OBJECTIVE: To evaluate the curative effect and safety of endoscopic full
      thickness resection (EFR) in the treatment of gastric tumor originated from the
      muscularis propria.? METHODS: Clinical data were collected from 34 patients, who
      underwent EFR of gastric tumor originated from muscularis propria, to observe the
      resection rate and complications from November 2012 to August 2014.? RESULTS: Of
      the 34 patients, 15 were male, 19 were female, with the age of 38.3-70.6 (52.3+/
      4.3) years old. The lesions of 25 patients located in the fundus of stomach and
      the rest was in the gastric body. EFR was successfully performed in the 34
      patients with no need for surgery. The complete resection rate was 100%. Lesion
      diameter ranged from 1.0 to 5.0 (2.8+/-1.2) centimeters. The operation time was
      50-100 (76.5+/-18.2) min. Patients with pneumoperitoneum were relieved after
      abdominal puncture exhaust, without post-operation bleeding and perforation. The
      hospitalization duration was 3-5 (3.6+/-0.8) days. Except 1 case, the remaining
      33 cases were spindle cell tumors, consistent with the results of
      immunohistochemistry. The risk for two lesions with 4.5 cm and 5.0 cm was
      moderate. The risk of invasion was low or very low in the remaining 31 cases.
      Among them, 2 stromal tumors near the cardia showed a differentiation tendency
      toward smooth muscle. No lesion residual or recurrence happened during the follow
      up period (range 5-23 months) in 34 cases. ? CONCLUSION: EFR is a safe and
      effective method for gastric tumor originated from muscularis propria.

PMID- 27033793
TI  - [Analysis of mortality among children under 5 years old ?in Hunan in 2013].
AB  - OBJECTIVE: To analyze the main causes and characteristics for death among
      children under 5 years old so as to provide the basis for taking strategic
      measures for child survival, development, protection.? METHODS: The data of 5 747
      dead children, who were under 5 years old in different cities of Hunan Province
      in 2013, were retrospectively analyzed. Descriptive statistic methods were used
      to analyze the causes and characteristics of death among the children. Chi-square
      test was used to analyze the differences of mortality rate.? RESULTS: In 2013,
      the under-5 mortality rate (U5MR) was 7.000/00. By linear trend chi-square test,
      the U5MR from 2002 to 2013 showed a tendency toward decrease (P<0.05). Among the
      death causes, drowning was the major one and it accounted for 13.35% of death,
      following by congenital heart disease, premature birth or low birth weight,
      pneumonia and accidental suffocation, with a ratio at 12.65%, 11.66%, 10.82%, and
      8.13%, respectively. After chi-square test, there were differences in U5MR in the
      cities of Hunan Province in 2013 (chi2=163.185, P<0.05).? CONCLUSION: Compared
      with previous data, the U5MR in 2013 is decreased significantly. There are
      differences in U5MR in the cities, and there are also difference in U5MR between
      city and rural area in Hunan Province in 2013. Among the death causes for
      children under 5 years old in Hunan Province in 2013, drowning is in the major
      one, and pneumonia is the fourth one.

PMID- 27033794
TI  - [Application of cryoablation in ?minimally invasive mitral valve surgery].
AB  - OBJECTIVE: To summarize the clinical data of patients who experienced
      cryoablation in minimally invasive mitral valve surgery and to explore safety and
      effectiveness of the surgery.? METHODS: We retrospectively collected the clinical
      data of patients who experienced cryoablation in minimally invasive mitral valve
      surgery in Department of Cardiovascular of Second Xiangya Hospital from August
      2013 to July 2015. Through a right side (4-6 cm) thoracotomy, femoral cannulation
      and aortic cross-clamp by Chitwood clamper was performed, left atrium was entered
      from interatrial groove. Modified left and right side cryomaze followed by valve
      surgery was finished. The left atrial appendage was excluded by oversewing from
      endocardial surface. The cardiopulmonary bypass time, cross-clamp time, duration
      in hospital were recorded. The heart rhythm of 3 consecutive post operation days,
      at 7th day, 3 months, 6 months, 12 months or 18 months after the surgery was
      monitered by 12-leads electrical cardiogram.? RESULTS: No death was observed in
      this group. Reexploration for bleeding was conducted for one case. Operation
      time, CBP time and cross-clamp time was (197.4+/-27.2), (103.6+/-20.3)and (65.3+/
      15.7) min, respectively. Duration in ICU and hospital was (1.2+/-0.4) and (9.2+/
      1.6) d, respectively. The ratio of sinus rhythm restoration right after surgery
      was 97.1%. The ratio of sinus rhythm restoration at the time of hospital
      discharge was 94.3%. No motality was found in follow-up. The ratio of sinus
      rhythm restoration at 3, 6, 12,18 months after the surgery was 94.3%, 93.5%,
      90.5%, 93.3%, respectively.? CONCLUSION: Right minimal invasive thoracoscopic
      assisted cryoablation in mitral valve surgery is quite effective in the treatment
      of atrial fibrillation, displaying the advantages of less complications, motality
      and hospitalization.

PMID- 27033795
TI  - [Effect of T4 thoracoscopic sympathectomy on ?plantar hyperhidrosis in patients
      with ?primary palmoplantar hyperhidrosis].
AB  - OBJECTIVE: To evaluate the effect of video-assisted thoracoscopic sympathectomy
      at the T4 level on plantar hyperhidrosis in the treatment of palmoplantar
      hyperhidrosis.? METHODS: The clinical data of 28 patients with primary
      palmoplantar hyperhidrosis, who were admited in our hospital from June 2009 to
      May 2014, was analyzed. All patients were qualified to bilateral thoracoscopic
      transaction of the sympathetic chain at the thoracic level T4. Patients completed
      a self-administered hyperhidrosis questionnaire and scoring before and after
      procedure. Follow-up data were obtained at 1 and 6 months after the surgery.?
      RESULTS: Endoscopic thoracic sympathectomy at the thoracic level T4 was performed
      successfully for all cases. Palmar hyperhidrosis was completely alleviated after
      the operation and no recurrence was observed during follow-up. The ratio for
      initial improvement of plantar hyperhidrosis was 28.6% (8/28) at 1 month after
      the surgery followed by a recurrence of plantar hyperhidrosis. No case continued
      to show the improvement of palmoplantar hyperhidrosis at 6 months after the
      sympathectomy. Twenty-seven patients (96.4%) were very satisfied with the outcome
      of the operation, 1 patient (3.6%) satisfied and no patient regretted the
      surgical procedure.? CONCLUSION: T4 thoracoscopic sympathectomy could initialliy
      alleviate plantar hyperhidrosis in some patients with palmoplantar hyperhidrosis,
      but the improvement was not sustained over a long period. It could not be used to
      treat plantar hyperhidrosis.

PMID- 27033796
TI  - [Clinical study on ambulatory surgery for thyroid].
AB  - OBJECTIVE: To evaluate the advantages and clinical value regarding the ambulatory
      surgery for thyroid.? METHODS: A total of 66 patients (including 16 cases of
      differentiated thyroid cancer, 50 cases of benign thyroid tumors) from June 2014
      to April 2015 in Center for Ambulatory Surgery of Xiangya Hospital were enrolled
      for this study and served as an exprimental group. All patients met pre
      established ambulatory surgery criteria for thyroid. According to medical
      records, 133 patients with similar conditions to the experimental group were
      chosen as a control group. All of operations in two groups were completed by the
      same doctors. The time of operation, amount of bleeding during operation,
      drainage after the operation, operation method, resection range, histological
      features, surgical complications, average days of hospitalization, average
      hospitalization cost, the rate of re-admission and the satisfaction of patients
      were compared between the 2 groups. ? RESULTS: Time of operation and amount of
      bleeding during operation were not significantly different between the 2 groups
      (P>0.05). In terms of drainage after operation and resection range, there were
      obvious differences between the 2 groups (P<0.05). The resection range and the
      amounts of drainage in the experimental group were less than those in the control
      group. More patients in the experimental group chose endoscopic thyroid surgery
      compared with those in the control group (P<0.05). The rate of surgical
      complications and re-admission was not different (P>0.05), but average days of
      hospitalization and average hospitalization cost were less in the experimental
      group (P<0.05). Patients were satisfied with ambulatory thyroid surgery
      (P<0.05).? CONCLUSION: Under certain criteria, ambulatory surgery for thyroid is
      a new operation method, which is safe, high-efficient, convenient, economy and
      time-efficient. It can decrease average days of hospitalization and average
      hospitalization cost obviously, and provide a reasonable choice for certain
      patients. The selection of endoscopic thyroid surgery was not conflict with
      selection of ambulatory thyroid surgery.

PMID- 27033797
TI  - [Diagnostic analysis for 52 cases of gastrointestinal neuroendocrine tumor].
AB  - OBJECTIVE: To investigate the clinical features, diagnosis, treatments and
      prognosis for gastrointestinal neuroendocrine tumors (GI-NETs).? METHODS: Clincal
      data of 52 patients, who were diagnosed as GI-NETs between January 2004 and
      October 2014, were reviewed. The patients were divided into a local excision
      group (n=21) and a transabdominal excision group (n=30), and the major clinical
      features, treatment modalities and outcomes were analyzed.? RESULTS: The clinical
      features of GI-NETs were nonspecific, and most of the clinical manifestation were
      local invasiveness. CT scan was lack of specific findings. GI-NETs greater than 1
      cm often showed local incrassation, upheaval and soft tissue shadow. In the case
      of lager GI-NETs, necrosis and moderate enhancement could be seen. Positive ratio
      for expression of chromogranin A (CgA) and synaptophysin (Syn) in the 52 cases of
      specimen were 63.5% and 88.5%, respectively. Except 1 patient, whose surgery was
      canceled because of poor health, other 51 patients were treated with surgery
      through different approaches. Among them, 30 cases were transabdominal resection
      (57.7%) and 21 were local resection (40.4%). Chemotherapy and/or radiotherapy was
      only applied for 7 patients. After a follow-up of 40 (3-132) months, 7 patients
      died, the rest were alive. The median survival in the local resection group and
      the transabdominal resection group was 43.0 and 39.5 months, respectively
      (P>0.05).? CONCLUSION: Under the condition of fully understanding the biological
      characteristics of GI-NETs, early diagnosis and timely personalized treatment is
      hopeful to reach the relative good prognosis and survival.

PMID- 27033798
TI  - [Therapeutic effect of long-term noninvasive positive pressure ventilation on
      stable chronic obstructive pulmonary disease: a systematic review].
AB  - OBJECTIVE: To determine the efficacy of long-term noninvasive positive pressure
      ventilation (NPPV) on stable chronic obstructive pulmonary disease (COPD). ?
      METHODS: Information was collected from the database of China National Knowledge
      Infrastructure (CNKI), WanFang, WeiPu, PubMed, EMbase, CBM (from the begining to
      October 2014). Statistical analysis was performed with the Cochrane
      Collaboration's software RevMan 5.2.? RESULTS: A total of 23 trials involving 1
      200 patients were included. RESULTS showed that NPPV can reduce PaCO2 and improve
      PaO2 in patients with stable COPD; two years of NPPV can delay the decline in
      forced expiratory volume in one second (FEV1) and forced vital capacity (FVC),
      increase six-minutes walk distance (6MWD) and reduce mortality in patients with
      stable COPD (OR=0.62, 95% CI 0.47 to 0.82).? CONCLUSION: NPPV can improve the
      arterial blood gas in patients, and the longer the application of NPPV, the
      better effect; NPPV can increase exercise endurance and improve the quality of
      life for the patients; long application of NPPV can delay the decline in FEV1and
      FVC (2 years or longer); NPPV can reduce the mortality of COPD patients.

PMID- 27033799
TI  - [Progress in study on effect of harmine on bone and cartilage metabolism].
AB  - Harmine, a beta-carboline alkaloid, is widely distributed in the plants, animals
      as well as in human tissues and body fluids. Harmine has various types of
      pharmacological activities including antimicrobial, antiplasmodial,
      antioxidative, antitumor, antimutagenic, antidiabetic, vasorelaxant and central
      excitation properties. Moreover, it can exert regenerative and protective effects
      on bone and cartilage tissues by regulating the proliferation, differentiation
      and metabolism of osteoclasts, osteoblasts and chondrocytes. These features make
      harmine a novel candidate for the prevention and treatment of bone and cartilage
      diseases, such as osteoporosis, bone fracture and osteoarthritis. 

PMID- 27033800
TI  - [TRPM7 and tumor].
AB  - The transient receptor potential (TRP) family is a superfamily of cation channels
      located on the cell membrane. Transient receptor potential melastatin (TRPM) 7, a
      member of the TRPM subgroup of TRP channels, and was the most representative
      biofunctional membrane protein. It conducts calcium and monovalent cations to
      depolarize cells and increase intracellular calcium. It is capable of
      phosphorylating TRPM7 and other substrates. TRPM7 can mediate sensory
      transmission, regulate cellular Ca2+ and Mg2+ homeostasis and affect embryonic
      development. Abnormal expression and/or activity of the TRPM7 channel kinase is
      involved in a variety of diseases, particularly the development and progression
      of cancer. TRPM7 channel-kinase is essential for cellular processes, such as
      proliferation, survival, differentiation, growth, and migration. 

PMID- 27033801
TI  - Generation of cloned mice and nuclear transfer embryonic stem cell lines from
      urine-derived cells.
AB  - Cloning animals by nuclear transfer provides the opportunity to preserve
      endangered mammalian species. However, there are risks associated with the
      collection of donor cells from the body such as accidental injury to or death of
      the animal. Here, we report the production of cloned mice from urine-derived
      cells collected noninvasively. Most of the urine-derived cells survived and were
      available as donors for nuclear transfer without any pretreatment. After nuclear
      transfer, 38-77% of the reconstructed embryos developed to the morula/blastocyst,
      in which the cell numbers in the inner cell mass and trophectoderm were similar
      to those of controls. Male and female cloned mice were delivered from cloned
      embryos transferred to recipient females, and these cloned animals grew to
      adulthood and delivered pups naturally when mated with each other. The results
      suggest that these cloned mice had normal fertility. In additional experiments,
      26 nuclear transfer embryonic stem cell lines were established from 108 cloned
      blastocysts derived from four mouse strains including inbreds and F1 hybrids with
      relatively high success rates. Thus, cells derived from urine, which can be
      collected noninvasively, may be used in the rescue of endangered mammalian
      species by using nuclear transfer without causing injury to the animal. 

PMID- 27033802
TI  - The experience of scar management for adults with burns: An interpretative
      phenomenological analysis.
AB  - Burns can have both physical and psychological effects on individuals. Pressure
      garments and silicone gels are used to improve the aesthetic appearance and
      functions of the skin, but these treatments have been associated with various
      physical, emotional, sexual and social difficulties. Interpretative
      phenomenological analysis (IPA) was used to explore participants' experiences of
      scar management. IPA examines individual experiences before comparing results
      across cases, and is suited to capture the different ways in which individuals
      experience a phenomena as well as cautiously looking at patterns across cases.
      Eight burn patients who had experienced scar management, including pressure
      garments, were interviewed. Two superordinate themes were identified:
      Assimilation of Pressure Garment Identity, and Psychosocial Functions of the
      Pressure Garments. The findings offered insight into the positive and negative
      experiences of scar management, describing the diverse personal and social
      functions of the pressure garments and how they became integrated into
      participants' identities. By understanding the individual nature of these
      experiences, healthcare professionals can enhance support around these issues and
      potentially aid adherence to treatment. Further research with different
      demographic groups as well as for other burn treatments would be useful to
      develop and contextualise these findings. 

PMID- 27033803
TI  - Disturbed diurnal rhythm of three classical phase markers in the chronic mild
      stress rat model of depression.
AB  - Disturbances of circadian rhythms have been suggested to be a causal factor in
      the development of major depressive disorder. However, the mechanisms underlying
      the association between circadian rhythm abnormalities and mood disorders are
      still unknown. In the current study the association between diurnal pattern of
      key phase markers (melatonin, corticosterone, and core body temperature) and
      anhedonic-like behavior was investigated using the highly validated rat chronic
      mild stress (CMS) model of depression. Phase marker measurements were done after
      3.5 weeks of CMS in 48 control rats and 48 anhedonic-like rats at 6 time points
      within 24h. The results showed that anhedonic-like behavior associates with
      changes in all three phase markers: an increased dark phase melatonin secretion,
      an additional peak in corticosterone level in the beginning of the light phase,
      and hypothermia in the dark phase. The result adds to the validity of the CMS
      model in general and in particular to be adequate as a model for studying the
      chronobiology of depressive disorder. 

PMID- 27033804
TI  - Molecular and functional characterization of peptidoglycan-recognition protein
      SC2 (PGRP-SC2) from Nile tilapia (Oreochromis niloticus) involved in the immune
      response to Streptococcus agalactiae.
AB  - PGRP-SC2, the member of PGRP family, plays an important role in regulation of
      innate immune response. In this paper, a PGRP-SC2 gene of Nile tilapia,
      Oreochromis niloticus (designated as On-PGRP-SC2) was cloned and its expression
      pattern under the infection of Streptococcus agalactiae was investigated.
      Sequence analysis showed main structural features required for amidase activity
      were detected in the deduced amino acid sequence of On-PGRP-SC2. In healthy
      tilapia, the On-PGRP-SC2 transcripts could be detected in all the examined
      tissues, with the most abundant expression in the muscle. When infected with S.
      agalactiae, there was a clear time-dependent expression pattern of On-PGRP-SC2 in
      the spleen, head kidney and brain. The assays for the amidase activity suggested
      that recombinant On-PGRP-SC2 protein had a Zn(2+)-dependent PGN-degrading
      activity. Moreover, our works showed that recombinant On-PGRP-SC2 protein could
      significantly reduce bacterial load in target organs attacked by S. agalactiae.
      These findings indicated that On-PGRP-SC2 may play important roles in the immune
      response to S. agalactiae in Nile tilapia. 

PMID- 27033805
TI  - Differential expression of CuZnSOD gene under low temperature stress in noble
      scallop Chlamys nobilis with different carotenoid content.
AB  - The noble scallop Chlamys nobilis belongs to a warm-water mollusk and has been
      cultured in the sea of southern China since 1980s'. However, accidents of massive
      mortality have often occurred during the winter, and one of the reasons could be
      accumulation of harmful reactive oxygen species caused by lower temperature.
      Carotenoids are well known for their anti-oxidant function. To investigate
      whether carotenoids do play a role in mollusks' antioxidant defense system under
      lower temperature stress, an acute lower temperature experiment was conducted by
      using two types of scallops: the orange with higher carotenoids content and the
      brown with lower carotenoids content. Their CuZnSOD gene was cloned, mRNA
      expression levels were determined, and SOD activity and carotenoids content were
      measured. The complete CuZnSOD cDNA consists of 1078 nucleotides with an open
      reading frame encoding 154 amino acid residues, which has high identity with that
      of its sister species Chlamys farreri. The mRNA expression levels in both the
      mantle and gill from the orange scallops were significantly higher (P < 0.05)
      than that of the brown ones, but the result was the opposite in the blood. SOD
      activity in the mantle and gill from the orange scallops was significantly higher
      than (P < 0.05) that from the brown ones. Further, significantly positive
      correlations were found among CuZnSOD gene transcript levels, SOD activity and
      total carotenoids content in the orange scallops. The present results suggested
      that carotenoids could play roles in antioxidant defense system by upregulating
      gene expression under lower temperature stress in the noble scallop. 

PMID- 27033806
TI  - Multi-species protein similarity clustering reveals novel expanded immune gene
      families in the eastern oyster Crassostrea virginica.
AB  - Comparative genomics research in non-model species has highlighted how
      invertebrate hosts possess complex diversified repertoires of immune molecules.
      The levels of diversification in particular immune gene families appear to differ
      between invertebrate lineages and even between species within lineages,
      reflecting differences not only in evolutionary histories, but also in life
      histories, environmental niches, and pathogen exposures. The goal of this
      research was to identify immune-related gene families experiencing high levels of
      diversification in eastern oysters, Crassostrea virginica. Families containing 1)
      transcripts differentially expressed in eastern oysters in response to bacterial
      challenge and 2) a larger number of transcripts compared to other species
      included those coding for the C1q and C-type lectin domain containing proteins
      (C1qDC and CTLDC), GTPase of the immune-associated proteins (GIMAP), scavenger
      receptors (SR), fibrinogen-C domain containing proteins (also known as FREPs),
      dopamine beta-hydrolase (DBH), interferon-inducible 44 (IFI44), serine protease
      inhibitors, apextrin, and dermatopontin. Phylogenetic analysis of two of the
      families significantly expanded in bivalves, IFI44 and GIMAP, showed a patchy
      distribution within both protostomes and deuterostomes, suggesting multiple
      independent losses and lineage-specific expansions. Increased availability of
      genomic information for a broader range of non-model species broadly distributed
      through vertebrate and invertebrate phyla will likely lead to improved knowledge
      on mechanisms of immune-gene diversification. 

PMID- 27033808
TI  - ES&T's Best Papers of 2015.

PMID- 27033807
TI  - Recent progress in ubiquitin and ubiquitin-like protein (Ubl) signaling.

PMID- 27033809
TI  - PSA ANNUAL MEETING 2009.

PMID- 27033810
TI  - IMPACTS OF SOLAR UV RADIATION ON THE PHOTOSYNTHESIS, GROWTH, AND UV-ABSORBING
      COMPOUNDS IN GRACILARIA LEMANEIFORMIS (RHODOPHYTA) GROWN AT DIFFERENT NITRATE
      CONCENTRATIONS(1).
AB  - Solar ultraviolet radiation (UVR, 280-400 nm) is known to affect macroalgal
      physiology negatively, while nutrient availability may affect UV-absorbing
      compounds (UVACs) and sensitivity to UVR. However, little is known about the
      interactive effects of UVR and nitrate availability on macroalgal growth and
      photosynthesis. We investigated the growth and photosynthesis of the red alga
      Gracilaria lemaneiformis (Bory) Grev. at different levels of nitrate (natural or
      enriched nitrate levels of 41 or 300 and 600 MUM) under different solar radiation
      treatments with or without UVR. Nitrate-enrichment enhanced the growth, resulted
      in higher concentrations of UVACs, and led to negligible photoinhibition of
      photosynthesis even at noon in the presence of UVR. Net photosynthesis during the
      noon period was severely inhibited by both ultraviolet-A radiation (UVA) and
      ultraviolet-B radiation (UVB) in the thalli grown in seawater without enriched
      nitrate. The absorptivity of UVACs changed in response to changes in the PAR dose
      when the thalli were shifted back and forth from solar radiation to indoor low
      light, and exposure to UVR significantly induced the synthesis of UVACs. The
      thalli exposed to PAR alone exhibited higher growth rates than those that
      received PAR + UVA or PAR + UVA + UVB at the ambient or enriched nitrate
      concentrations. UVR inhibited growth approximately five times as much as it
      inhibited photosynthesis within a range of 60-120 MUg UVACs . g(-1) (fwt) when
      the thalli were grown under nitrate-enriched conditions. Such differential
      inhibition implies that other metabolic processes are more sensitive to solar UVR
      than photosynthesis. 

PMID- 27033811
TI  - PHOTOPHYSIOLOGY OF A TURF ALGAL COMMUNITY: INTEGRATED RESPONSES TO AMBIENT LIGHT
      AND STANDING BIOMASS(1).
AB  - This study investigated the variation in the relationship between photosynthesis
      and ambient light (P-E curves) for turf algal communities on a temperate reef off
      the coast of South Australia, analyzing the integrated effects of ambient light
      and standing biomass. The photophysiology of turfs was studied in situ on a
      seasonal basis, examining algal communities growing on artificial substrate
      (plates) at depths of 4 m and 10 m. P-E curves and estimates for the photokinetic
      parameters (Pm , Rd , alpha, Ek , and Ec ) were obtained through oxygen evolution
      methods, using an automated underwater respirometer. Photoacclimation responses
      to changes in ambient light were strongly affected by the biomass of the
      community. Pm showed an inverse relationship to standing biomass, irrespective of
      depth and season, which was considered to be a response to self-shading and
      boundary layer effects. Biomass effects imposed a high variance on estimates for
      all photosynthetic parameters, overshadowing differences observed for season and
      depth. Biomass also affected photoinhibition on turf communities, where
      significant afternoon depression of photosynthesis was observed in sparse turf
      patches when compared to denser patches. High areal productivity rates were
      maintained across all seasons with a significant decrease only being observed
      during winter. 

PMID- 27033812
TI  - SPATIAL AND TEMPORAL COMPARISON OF ALGAL BIODIVERSITY AND BENTHIC COVER AT
      GARDNER PINNACLES, NORTHWESTERN HAWAI'IAN ISLANDS(1).
AB  - Papahanaumokuakea Marine National Monument in the Northwestern Hawai'ian Islands
      is the second largest marine protected area in the world, providing an
      opportunity for scientists to understand natural ecosystem fluctuations in
      subtropical marine communities with little anthropogenic impact. Gardner
      Pinnacles is composed of two emergent basaltic rocks and has the smallest land
      area of any island in the Northwestern Hawai'ian Island chain but has among the
      largest submerged reef area. Gardner Pinnacles is also among the least
      anthropogenically impacted island in the Hawai'ian Archipelago, although a
      thriving lobster and bottomfish industry existed in the area for many years. This
      study assesses nearshore algal biodiversity and percent cover at Gardner
      Pinnacles to examine interannual differences in community dynamics and places
      them in an ecosystem context by also examining associated invertebrate and fish
      communities. Biodiversity surveys increased the number of known eukaryotic algal
      species occurring in marine environments immediately adjacent to the emergent
      portion of Gardner Pinnacles from 31 to 77. Algal percent cover, specifically
      populations of the green alga Microdictyon setchellianum M. Howe, varied
      dramatically between sampling years, possibly in response to seasonal
      differences. Towed-diver surveys revealed that macroalgae covered >90% of the
      substrate during the 2003 sampling period but returned to 2000 levels (1%-35%
      cover) by 2004 without any detectable damage to other reef organisms. Fish
      communities remained statistically similar between sampling years, and percent
      cover of live coral around the island did not exceed 7%. 

PMID- 27033813
TI  - DISINTEGRATION OF THE CELLS OF SIPHONOUS GREEN ALGA CODIUM EDULE (BRYOPSIDALES,
      CHLOROPHYTA) UNDER MILD HEAT STRESS(1).
AB  - The siphonous green alga Codium edule P. C. Silva (Bryopsidales, Chlorophyta) has
      the highest covering ratio among the macroalgae on the coral reef of Nanwan Bay
      in southern Taiwan, but its population in the subtidal region drastically
      decreases from July to September each year. The objective of this study was to
      determine whether the high temperature of summer could be the basis for this
      population decrease. Chlorophyll fluorescence measurements revealed that when the
      algae were incubated at 35 degrees C (a temperature that can be reached in
      southern Taiwan during the summer), their photosynthetic activities were almost
      completely inhibited after about 8 h. The circadian rhythm of photosynthesis was
      disrupted at a temperature as low as 32 degrees C. TEM studies showed that 4 h
      incubation at 35 degrees C induced a decrease in turgidity accompanied by vacuole
      shrinkage and plasmolysis. The marked disintegrative changes, including damage to
      organelles, such as chloroplasts and nuclei, occurred after about 8 h, at which
      time central vacuoles collapsed and the cell interior was then filled with
      numerous small vesicles. Our results suggested that the rise in seawater
      temperature during the summer could be one of the major causes of the massive
      death of C. edule in the field. 

PMID- 27033814
TI  - EFFECTS OF MODERATE HEAT STRESS AND DISSOLVED INORGANIC CARBON CONCENTRATION ON
      PHOTOSYNTHESIS AND RESPIRATION OF SYMBIODINIUM SP. (DINOPHYCEAE) IN CULTURE AND
      IN SYMBIOSIS(1).
AB  - The influence of temperature and inorganic carbon (Ci ) concentration on
      photosynthesis was examined in whole corals and samples of cultured symbiotic
      dinoflagellates (Symbiodinium sp.) using combined measurements from a membrane
      inlet mass spectrometer and chl a fluorometer. In whole corals, O2 production at
      26 degrees C was significantly limited at Ci concentrations below ambient
      seawater (~2.2 mM). Further additions of Ci up to ~10 mM caused no further
      stimulation of oxygenic photosynthesis. Following exposure to 30 degrees C (2 d),
      net oxygen production decreased significantly in whole corals, as a result of
      reduced production of photosynthetically derived oxygen rather than increased
      host consumption. Whole corals maintained a rate of oxygen evolution around eight
      times lower than cultured Symbiodinium sp. at inorganic carbon concentrations <2
      mM, but cultures displayed greater levels of photoinhibition following heat
      treatment (30 degrees C, 2 d). Whole corals and cultured zooxanthellae differed
      considerably in their responses to Ci concentration and moderate heat stress,
      demonstrating that cultured Symbiodinium make an incongruous model for those in
      hospite. Reduced net oxygen evolution, in whole corals, under conditions of low
      Ci (<2 mM) has been interpreted in terms of possible sink limitation leading to
      increased nonphotochemical energy dissipation. The advantages of combined
      measurement of net gas exchange and fluorometry offered by this method are
      discussed. 

PMID- 27033815
TI  - OCCURRENCE OF LOROXANTHIN, LOROXANTHIN DECENOATE, AND LOROXANTHIN DODECENOATE IN
      TETRASELMIS SPECIES (PRASINOPHYCEAE, CHLOROPHYTA)(1).
AB  - The pigment composition of six species of Tetraselmis (Prasinophyceae) was
      analyzed using improved HPLC methods. All pigment extracts showed three peaks
      corresponding to unknown carotenoids. The isolated pigments were analyzed using
      UV-Vis spectroscopy, electrospray ionization-mass spectrometry (ESI-MS), and when
      carotenoid esters were suspected, gas chromatography-mass spectrometry (GC-MS) of
      the methyl ester and dimethyloxazoline derivative of the corresponding fatty
      acid. The new pigments were determined to be loroxanthin, loroxanthin 19-(2
      decenoate), and loroxanthin 19-(2-dodecenoate); this is the first time these
      pigments have been described in the genus Tetraselmis. Moreover, this is the
      first report of esterification of 2-decenoic acid to loroxanthin. The relative
      contents of these pigments depended on the light regime, with the lowest
      proportions measured at the highest photon flux density assayed. The implications
      of the identification of these pigments in the genus Tetraselmis for the pigment
      types previously described in the class Prasinophyceae are discussed. 

PMID- 27033816
TI  - DINOFLAGELLATE HOST-PARASITE STEROL PROFILES DICTATE KARLOTOXIN SENSITIVITY(1).
AB  - We examined the sterol profile of Karlodinium veneficum (D. Ballant.) J. Larsen,
      Akashiwo sanguinea (Hiraska) Ge. Hansen et Moestrup, Alexandrium tamarense (M.
      Lebour) Balech, Alexandrium affine (H. Inoue et Fukuyo) Balech, Gonyaulax
      polygramma F. Stein, and Gymnodinium instriatum (Freud. et J. J. Lee) Coats,
      along with their Amoebophyra parasites. There were no consistent sterol profiles
      that characterized the genus Amoebophyra. Instead, in five out of six
      comparisons, the host and parasite sterol profiles where highly correlated. The
      one exception, Amoebophyra sp. ex Alex. tamarense, was least like its host in
      sterol profile and also possessed the widest host range for infection. There was
      little correlation between host and parasite in fatty acid profiles, with the
      parasite being deficient in fatty acids characteristic of the plastid [e.g.,
      18:5(n-3) associated with galactolipids of the thylakoids, as previously
      published by Adolf et al. (2007)]. Those hosts and parasites with sterol profiles
      dominated by desmethyl sterols were most sensitive to karlotoxin toxicity. In the
      host-parasite pairs most sensitive to karlotoxin addition, recovery of the intact
      karlotoxin molecule was poorest. Given the sensitivity to karlotoxin, some
      species of Amoebophyra may avoid infection of K. veneficum. 

PMID- 27033817
TI  - EFFECT OF CHROMIUM(VI) ON PHOTOSYSTEM II ACTIVITY AND HETEROGENEITY OF
      SYNECHOCYSTIS SP. (CYANOPHYTA): STUDIED WITH IN VIVO CHLOROPHYLL FLUORESCENCE
      TESTS(1).
AB  - The inhibitory effect of Cr(VI) on the PSII of Synechocystis sp. was studied.
      Cr(VI) reduced O2 evolution and inhibited the water-splitting system in PSII. S
      states test and flash induction test showed that Cr(VI) exposure increased the
      proportion of inactivated PSII (PSIIX ) and PSIIbeta reaction centers, which
      increased the fluxes of dissipated energy. JIP test and QA (-) reoxidation test
      demonstrated that Cr(VI) treatment induces inhibition of electron transport from
      QA (-) to QB /QB (-) and accumulation of P680 (+) . More QA (-) had to be
      oxidized through S2 (QA QB )(-) charge recombination and oxidation by PQ9
      molecules in PSII under Cr(VI) stress. These changes finally decreased the index
      of photosynthesis performance. 

PMID- 27033818
TI  - NITZSCHIA OVALIS (BACILLARIOPHYCEAE) MONO LAKE STRAIN ACCUMULATES 1,4/2,5
      CYCLOHEXANETETROL IN RESPONSE TO INCREASED SALINITY(1).
AB  - The growth of microalgae in hypersaline conditions requires that cells accumulate
      osmoprotectants. In many instances, these are polyols. We isolated the diatom
      Nitzschia ovalis H. J. Arn. from the saline and alkaline water body Mono Lake
      (CA, USA). This isolate can grow in salinities ranging from 5 to 120 parts per
      thousand (ppt) of salt but normally at 90 ppt salinity. In this report, we
      identified the major polyol osmoprotectant as 1,4/2,5 cyclohexanetetrol by
      electron ionization-mass spectrometry (EI-MS), (1) H, (13) C nuclear magnetic
      resonance spectroscopy (NMR), and infrared (IR) and showed an increase in
      cellular concentration in response to rising salinity. This increase in the
      cyclitol concentration was evaluated by gas chromatography of the derived
      tetraacetylated cyclohexanetetrol obtaining an average of 0.7 fmol . cell(-1) at
      5 ppt and rising to 22.5 fmol . cell(-1) at 120 ppt. The 1,4/2,5
      cyclohexanetetrol was also detected in the red alga Porphyridium purpureum.
      Analysis of the free amino acid content in N. ovalis cultures exposed to changes
      in salinity showed that proline and lysine also accumulate with increased
      salinity, but the cellular concentration of these amino acids is about 10-fold
      lower than the concentration of 1,4/2,5 cyclohexanetetrol. The comparison of
      amino acid concentration per cell with cyclitol suggests that this polyol is
      important in compensating the cellular osmotic pressure due to increased
      salinity, but other physiological functions could also be considered. 

PMID- 27033819
TI  - EFFECT OF LATRUNCULIN B AND BREFELDIN A ON CYTOKINESIS IN THE BROWN ALGA
      SCYTOSIPHON LOMENTARIA (SCYTOSIPHONALES, PHAEOPHYCEAE)(1).
AB  - In zygotes of the brown alga Scytosiphon lomentaria (Lyngb.) Link, cytokinesis
      proceeds by growth of membranous sacs, which are formed by fusion of Golgi
      vesicles and flat cisternae accumulated at the future cytokinetic plane. It has
      been reported that depolymerization of actin filaments by latrunculin B does not
      inhibit mitosis. However, this molecule prevents the formation of the actin
      plate, which appears at the region of intermingled microtubules from each
      centrosome just before and during cytokinesis. In this study, zygotes treated
      with latrunculin B were observed using EM. Remarkably, this reagent inhibited the
      formation of flat cisternae. Golgi vesicles gathered around the midzone between
      the two daughter nuclei and fused with the plasma membrane there. As a result,
      the plasma membrane invaginated, in a complicated manner, into the cytoplasm.
      However, these invaginations of the plasma membrane never produced a continuous
      partition membrane. The ultrastructure of zygotes treated with brefeldin A, which
      prevents Golgi-mediated secretion, was also examined. Flat cisternae appeared at
      the future cytokinetic plane, and a new cell partition membrane was formed.
      However, the partition membrane became thick, because it was filled with
      amorphous material rather than the normal rigid fibrous material. These results
      suggested that actin is involved in the formation of flat cisternae, where it is
      necessary for completion of the new cell partition membrane, and that Golgi
      vesicles may play an important role in the deposition of cell wall material. 

PMID- 27033820
TI  - UNRAVELING THE REGULATION OF NITROGEN ASSIMILATION IN THE MARINE DIATOM
      THALASSIOSIRA PSEUDONANA (BACILLARIOPHYCEAE): DIURNAL VARIATIONS IN TRANSCRIPT
      LEVELS FOR FIVE GENES INVOLVED IN NITROGEN ASSIMILATION(1).
AB  - We examined the diurnal expression of five genes encoding nitrogen-assimilating
      enzymes in the marine diatom Thalassiosira pseudonana (Hust.) Hasle et Heimdal
      following a transition from NH4 (+) - to NO3 (-) -supplemented media. The
      accumulation of nia transcripts (encoding nitrate reductase, NR) following the
      transition to NO3 (-) -supplemented media was similar to previously reported
      changes in NR abundance and activity. Nia mRNA levels varied diurnally, and the
      diurnal oscillations were abolished when cells were transferred to continuous
      light. Genes encoding chloroplastic (niiA) and cytosolic (nirB) nitrite
      reductases were identified in the genome of T. pseudonana. NiiA and nirB
      transcript levels increased within 2 h following the addition of NO3 (-) and
      varied diurnally. Patterns of diurnal variation in nia, niiA, and glnII (encoding
      the chloroplast-localized glutamine synthetase) mRNA abundances were similar.
      NirB and glnN (encoding the cytosolic-localized glutamine synthetase) mRNA levels
      also oscillated diurnally; however, the oscillation was out of phase with nia,
      niiA, and glnII. We propose that NO3 (-) is assimilated into organic molecules in
      both the chloroplast and cytosol of diatoms and that enzymes encoded by nirB and
      glnN contribute to the ecologically important dark assimilation of NO3 (-)
      observed in marine diatoms. As with nia, the diurnal variations in niiA, nirB,
      glnII, and glnN were abolished when cells were transferred to continuous light.
      Our results demonstrate that transcript accumulation is not circadian controlled,
      but, rather, changes in metabolic pools triggered by light:dark (L:D) transitions
      may be important in regulating the cellular mRNA levels encoding these key
      nitrogen assimilating enzymes. 

PMID- 27033821
TI  - METAL-INDUCED REACTIVE OXYGEN SPECIES PRODUCTION IN CHLAMYDOMONAS REINHARDTII
      (CHLOROPHYCEAE)(1).
AB  - Toxic effects of metals appear to be partly related to the production of reactive
      oxygen species (ROS), which can cause oxidative damage to cells. The ability of
      several redox active metals [Fe(III), Cu(II), Ag(I), Cr(III), Cr(VI)], nonredox
      active metals [Pb(II), Cd(II), Zn(II)], and the metalloid As(III) and As(V) to
      produce ROS at environmentally relevant metal concentrations was assessed. Cells
      of the freshwater alga Chlamydomonas reinhardtii P. A. Dang. were exposed to
      various metal concentrations for 2.5 h. Intracellular ROS accumulation was
      detected using an oxidation-sensitive reporter dye, 5-(and-6)-carboxy-2',7'
      dihydrodifluorofluorescein diacetate (H2 DFFDA), and changes in the fluorescence
      signal were quantified by flow cytometry (FCM). In almost all cases, low
      concentrations of both redox and nonredox active metals enhanced intracellular
      ROS levels. The hierarchy of maximal ROS induction indicated by the increased
      number of stained cells compared to the control sample was as follows: Pb(II) >
      Fe(III) > Cd(II) > Ag(I) > Cu(II) > As(V) > Cr(VI) > Zn(II). As(III) and Cr(III)
      had no detectable effect. The effective free metal ion concentrations ranged from
      10(-6) to 10(-9)  M, except in the case of Fe(III), which was effective at 10(
      18)  M. These metal concentrations did not affect algal photosynthesis.
      Therefore, a slightly enhanced ROS production is a general and early response to
      elevated, environmentally relevant metal concentrations. 

PMID- 27033822
TI  - GENETIC AND MORPHOLOGICAL ANALYSES OF THE SOUTHERN BULL KELP DURVILLAEA
      ANTARCTICA (PHAEOPHYCEAE: DURVILLAEALES) IN NEW ZEALAND REVEAL CRYPTIC
      SPECIES(1).
AB  - Many macroalgae exhibit considerable intraspecific morphological variation, but
      whether such variation reflects phenotypic plasticity or underlying genetic
      differences is often poorly understood. We quantified both morphological and
      genetic variation of 96 plants from seven field sites across eastern South
      Island, New Zealand, to assess genetic differences between morphotypes of the
      southern bull kelp Durvillaea antarctica (Cham.) Har. Consistent DNA sequence
      differentiation across mitochondrial, plastid, and nuclear loci was correlated
      with two broadly sympatric morphotypes: "cape" and "thonged." These ecologically,
      morphologically, and genetically distinct bull-kelp lineages were previously
      considered to be environmentally determined phenotypes with no underlying genetic
      basis. Interestingly, the sheltered "cape" lineage appears essentially
      genetically uniform across its South Island range, whereas the exposed "thonged"
      lineage exhibits marked phylogeographic structure across its range. Results
      suggest that D. antarctica in New Zealand comprises two reproductively isolated
      species. 

PMID- 27033823
TI  - PHYLOGENETIC POSITION OF ATTHEYA LONGICORNIS AND ATTHEYA SEPTENTRIONALIS
      (BACILLARIOPHYTA)(1).
AB  - The phylogenetic position of diatoms belonging to the genus Attheya is presently
      under debate. Species belonging to this genus have been placed in the subclasses
      Chaetocerotophycidae and Biddulphiophycidae, but published phylogenetic trees
      based on 18S rDNA, morphology, and sexual reproduction indicate that this group
      of diatoms may be a sister group of the pennates. To clarify the position of
      Attheya, we studied the morphology, 18S rDNA, 16S rDNA of the chloroplasts, the
      rbcL large subunit (LSU) sequences of the chloroplasts, and the sterol
      composition of three different strains of Attheya septentrionalis (Ostrup) R. M.
      Crawford and one strain of Attheya longicornis R. M. Crawford et C. Gardner.
      These data were compared with data from more than 100 other diatom species,
      covering the whole phylogenetic tree, with special emphasis on species belonging
      to the genera that have been suggested to be related to the genus Attheya. All
      data suggest that the investigated Attheya species form a separate group of
      diatoms, and there is no indication that they belong to either the
      Chaetocerotophycidae or the Biddulphiophycidae. Despite applying these various
      approaches, we were unable to determine the exact phylogenetic position of the
      investigated Attheya species within the diatoms. 

PMID- 27033824
TI  - BIOGEOGRAPHIC ANALYSIS OF THE GLOBALLY DISTRIBUTED HARMFUL ALGAL BLOOM SPECIES
      ALEXANDRIUM MINUTUM (DINOPHYCEAE) BASED ON rRNA GENE SEQUENCES AND MICROSATELLITE
      MARKERS(1).
AB  - The toxic dinoflagellate Alexandrium minutum Halim is one of three species that
      comprise the "minutum" species complex. This complex is notable due to its role
      in the etiology of paralytic shellfish poisoning (PSP). Recent increases in PSP
      incidence and the geographic expansion of toxin-producing Alexandrium
      dinoflagellates have prompted the intensive examination of genetic relationships
      among globally distributed strains to address questions regarding their present
      distribution and reasons for their apparent increase. The biogeography of A.
      minutum was studied using large subunit ribosomal DNA gene (LSU rRNA) and
      internal transcribed spacer (ITS) sequences and genotypic data from 12
      microsatellite loci. rRNA gene and ITS sequencing data distinguished between two
      clades, herein termed the "Global" and the "Pacific"; however, little to no
      resolution was seen within each clade. Genotypic data from 12 microsatellite loci
      provided additional information regarding genetic relationships within the Global
      clade, but it was not possible to amplify DNA from the Pacific clade using these
      markers. With the exception of isolates from Italy and Spain, strains generally
      clustered according to origin, revealing geographic structuring within the Global
      clade. Additionally, no evidence supported the separation of A. lusitanicum and
      A. minutum as different species. With the use of microsatellites, it is now
      possible to initiate studies on the origin, history, and genetic heterogeneity of
      A. minutum that were not previously possible using only rRNA gene sequence data.
      This study demonstrates the power of combining a marker with intermediate
      resolution (rRNA sequences) with finer-scale markers (microsatellites) to examine
      intraspecies variability among globally distributed isolates and represents the
      first effort to employ this technique in A. minutum. 

PMID- 27033825
TI  - PHYLOGENY AND SYSTEMATICS OF EUGLENA (EUGLENACEAE) SPECIES WITH AXIAL, STELLATE
      CHLOROPLASTS BASED ON MORPHOLOGICAL AND MOLECULAR DATA-NEW TAXA, EMENDED
      DIAGNOSES, AND EPITYPIFICATIONS(1).
AB  - Morphological and molecular studies, as well as original literature
      reexamination, necessitate establishment of five Euglena species with a single
      axial, stellate chloroplast [Euglena viridis (O. F. Muller) Ehrenberg 1830,
      Euglena pseudoviridis Chadefaud 1937, Euglena stellata Mainx 1926, Euglena
      pseudostellata sp. nov., and Euglena cantabrica Pringsheim 1956], three species
      with two chloroplasts (Euglena geniculata Dujardin ex Schmitz 1884, Euglena
      chadefaudii Bourrelly 1951, and Euglena pseudochadefaudii sp. nov.), and one
      species with three chloroplasts (Euglena tristella Chu 1946). The primary
      morphological features, allowing distinction of the considered species are the
      presence and the shape of mucocysts, as well as the number of chloroplasts.
      Spherical mucocysts occur in E. cantabrica and E. geniculata, while spindle
      shaped mucocysts are present in E. stellata, E. pseudostellata, E. chadefaudii,
      E. pseudochadefaudii, and E. tristella. No mucocysts are observed in E. viridis
      and E. pseudoviridis. Two new species (E. pseudochadefaudii sp. nov. and E.
      pseudostellata sp. nov.) differ from the respective species, E. chadefaudii and
      E. stellata, only at the molecular level. Molecular signatures and characteristic
      sequences are designated for nine distinguished species. Emended diagnoses for
      all and delimitation of epitypes for seven species (except E. viridis and E.
      tristella) are proposed. 

PMID- 27033826
TI  - TAXONOMIC STUDY OF TWO NEW GENERA OF FUSIFORM GREEN FLAGELLATES, TABRIS GEN. NOV.
      AND HAMAKKO GEN. NOV. (VOLVOCALES, CHLOROPHYCEAE)(1).
AB  - On the basis of LM, we isolated strains of two species of fusiform green
      flagellates that could be assigned to former Chlorogonium (Cg.) Ehrenb. One
      species, "Cg."heimii Bourr., lacked a pyrenoid in its vegetative cells and
      required organic compounds for growth. The other was similar to Cg. elongatum (P.
      A. Dang.) France and "Cg."acus Nayal, but with slightly smaller vegetative cells.
      Their molecular phylogeny was also studied based on combined 18S rRNA, RUBISCO
      LSU (rbcL), and P700 chl a-apoprotein A2 (psaB) gene sequences. Both species were
      separated from Chlorogonium emend., Gungnir Nakada and Rusalka Nakada, which were
      formerly assigned to Chlorogonium. They were accordingly assigned to new genera,
      Tabris Nakada gen. nov. and Hamakko (Hk.) Nakada gen. nov. as T. heimii (Bourr.)
      Nakada comb. nov. and Hk. caudatus Nakada sp. nov., respectively. Tabris is
      differentiated from other genera of fusiform green flagellates by its vegetative
      cells, which only have two apical contractile vacuoles and lack a pyrenoid in the
      chloroplast. Hamakko, on the other hand, is distinguishable by the fact that its
      pyrenoids in vegetative cells are penetrated by flattened thylakoid lamellae. 

PMID- 27033827
TI  - GENETIC DIVERSITY AND INTROGRESSION IN TWO CULTIVATED SPECIES (PORPHYRA YEZOENSIS
      AND PORPHYRA TENERA) AND CLOSELY RELATED WILD SPECIES OF PORPHYRA (BANGIALES,
      RHODOPHYTA)(1).
AB  - We investigated the genetic variations of the samples that were tentatively
      identified as two cultivated Porphyra species (Porphyra yezoensis Ueda and
      Porphyra tenera Kjellm.) from various natural populations in Japan using
      molecular analyses of plastid and nuclear DNA. From PCR-RFLP analyses using
      nuclear internal transcribed spacer (ITS) rDNA and plastid RUBISCO spacer regions
      and phylogenetic analyses using plastid rbcL and nuclear ITS-1 rDNA sequences,
      our samples from natural populations of P. yezoensis and P. tenera showed
      remarkably higher genetic variations than found in strains that are currently
      used for cultivation. In addition, it is inferred that our samples contain four
      wild Porphyra species, and that three of the four species, containing Porphyra
      kinositae, are closely related to cultivated Porphyra species. Furthermore, our
      PCR-RFLP and molecular phylogenetic analyses using both the nuclear and plastid
      DNA demonstrated the occurrence of plastid introgression from P. yezoensis to P.
      tenera and suggested the possibility of plastid introgression from cultivated P.
      yezoensis to wild P. yezoensis. These results imply the importance of collecting
      and establishing more strains of cultivated Porphyra species and related wild
      species from natural populations as genetic resources for further improvement of
      cultivated Porphyra strains. 

PMID- 27033828
TI  - GRACILARIA HUMMII SP. NOV. (GRACILARIALES, RHODOPHYTA), A NEW NAME FOR THE
      AGAROPHYTE "GRACILARIA CONFERVOIDES" HARVESTED IN NORTH CAROLINA DURING WORLD WAR
      II(1).
AB  - Gracilaria hummii Hommers. et Freshwater is proposed as a new name for the
      inshore cylindrical species found in North Carolina that was treated as
      Gracilaria confervoides (L.) Grev. during World War II, and more recently as G.
      verrucosa (Huds.) Papenf. Molecular evidence places G. hummii in the Gracilis
      group in Gracilaria together with G. gracilis (Stackh.) Steentoft, L. M. Irvine
      et Farnham, the name currently applied to specimens formerly identified as G.
      confervoides and G. verrucosa. G. hummii differs from G. gracilis in possessing
      shallower male conceptacles in which the spermatangial filament originates from a
      surface cortical cell rather than from a subcortical cell. The cystocarps are
      similar, except that the gonimoblasts of G. hummii are attached to the base of
      the pericarp by numerous, prominent thickened terminal tubular cells and because
      terminal tubular cells are absent above the midregion of the cystocarp or in the
      vicinity of the ostiole. The gonimoblasts are subtended by a bundle of
      longitudinally oriented, thick-walled secondary filaments of a type that has not
      been described before in Gracilaria but that may be characteristic of some other
      species. G. hummii occupies a basal position in the Gracilis-group and is
      distinct from all other cylindrical North Carolina Gracilaria species, according
      to the molecular and morphological evidence. 

PMID- 27033829
TI  - IMPROVED METHODS FOR THE ISOLATION OF CYANOBACTERIAL DNA FROM ENVIRONMENTAL
      SAMPLES(1).
AB  - DNA isolated from environmental samples often contains enzyme inhibitors
      disruptive to downstream molecular applications. Most of the existing methods of
      cyanobacterial DNA isolation do not effectively eliminate these inhibitors from
      sediment samples or cells collected from freshwater ecosystems. We describe
      improved methods based on the xanthogenate-SDS nucleic acid isolation (XS) method
      of Tillett and Neilan (2000). Our improved methods provided high-quality
      cyanobacterial DNA that could be amplified in PCR and digested with a restriction
      enzyme. Results were superior to several commercial kits. The DNA yield was also
      similar to that obtained via the standard XS method. These methods should provide
      valuable new tools for the expanded application of molecular genetics to
      limnological and oceanographic research. 

PMID- 27033830
TI  - FOURIER TRANSFORM INFRARED SPECTROSCOPY OF MICROALGAE AS A NOVEL TOOL FOR
      BIODIVERSITY STUDIES, SPECIES IDENTIFICATION, AND THE ASSESSMENT OF WATER
      QUALITY(1).
AB  - Fourier transform infrared (FTIR) spectrometry was used to study the spectral
      features of 12 eukaryotic and two prokaryotic species of microalgae. The algae
      were cultured in liquid media containing either NO3 (-) or NH4 (+) as the sole N
      source; for the NH4 (+) treatment, the algae were subjected to short-term (24 h)
      or long-term (1 month) incubations; for the hypersaline species, cells were also
      grown in the presence of 2 M NaCl. Over 500 spectra, acquired from at least three
      distinct cultures for each species, in each growth regime, were subjected to
      hierarchical cluster analysis (HCA) and were successfully separated according to
      their taxonomy, showing that the overall spectra were characteristic of each
      species and that this technique could be fruitfully employed to separate
      microalgal species living in a similar condition (as would be the case for a
      natural assemblage). In addition, in most cases, it was possible to differentiate
      between algae subjected to different growth treatments although belonging to the
      same species. We also demonstrated that it is possible to accurately identify
      species and determine the nutritional status of their environment of origin
      (e.g., N-source), provided that suitable FTIR spectral libraries are available.
      This study aims to provide the basis for the development of rapid, easy, and
      inexpensive methods for the evaluation of biodiversity in natural phytoplankton
      samples and to monitor the water quality of natural environments. 

PMID- 27033832
TI  - Processing of self-related kinematic information embedded in static handwritten
      characters.
AB  - Handwritten characters are generated by our own motor actions, and previous
      studies have shown that the manner in which such characters are perceived and
      generated is related. However, the temporal course of the neural activation
      involved in the processing of self-related kinematic information embedded in
      static handwritten characters remains to be identified. We applied event-related
      potential (ERP) recording while participants judged whether handwritten
      characters were self- or non-self-generated. To test the effects of the self
      related kinematic characteristics of static handwritten characters, we conducted
      two experiments in which the styles or familiarity of characters were
      manipulated. The ERP results indicated differences in brain activation between
      self- and non-self-written characters for the P250 component (250-350ms after
      stimulus onset) in right posterior regions and for the late positive component
      (LPC; 350-500ms after stimulus onset) in anterior midline regions; this was the
      case even when the handwritten characters were not generated in their usual form
      or were written for the first time. Therefore, our data indicate that self
      information embedded in handwritten characters involves both right-lateralized
      brain activation associated with bodily self-processing and anterior midline
      brain activation related to self-referential processing.

PMID- 27033831
TI  - Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis.
AB  - Recent advances in the genetics of amyotrophic lateral sclerosis (ALS) have
      provided key mechanistic insights to the pathogenesis of this devastating
      neurodegenerative disease. Among many etiologies for ALS, the identification of
      mutations and proteinopathies in two RNA binding proteins, TDP-43 (TARDBP or TAR
      DNA binding protein 43) and its closely related RNA/DNA binding protein FUS
      (fused in sarcoma), raises the intriguing possibility that perturbations to the
      RNA homeostasis and metabolism in neurons may contribute to the pathogenesis of
      these diseases. Although the similarities between TDP-43 and FUS suggest that
      mutations and proteinopathy involving these two proteins may converge on the same
      mechanisms leading to neurodegeneration, there is increasing evidence that FUS
      mutations target distinct mechanisms to cause early disease onset and aggressive
      progression of disease. This review focuses on the recent advances on the
      molecular, cellular and genetic approaches to uncover the mechanisms of wild type
      and mutant FUS proteins during development and in neurodegeneration. These
      findings provide important insights to understand how FUS mutations may perturb
      the maintenance of dendrites through fundamental processes in RNA splicing, RNA
      transport and DNA damage response/repair. These results contribute to the
      understanding of phenotypic manifestations in neurodegeneration related to FUS
      mutations, and to identify important directions for future investigations. This
      article is part of a Special Issue entitled SI:RNA Metabolism in Disease.

PMID- 27033833
TI  - Proteostasis impairment in ALS.
AB  - In physiological conditions the maintenance of the cellular proteome is a
      prerequisite for optimal cell functioning and cell survival. Additionally, cells
      need to constantly sense and adapt to their changing environment and associated
      stressors. Cells achieve this via a set of molecular chaperones, protein
      clearance pathways as well as stress-associated signaling networks which work
      together to prevent protein misfolding, its aggregation and accumulation in
      subcellular compartments. These processes together form the proteostasis network
      which helps in maintaining cellular proteostasis. Imbalance or impairment in this
      processes is directly linked to ageing associated disorders such as diabetes,
      cancer, stroke, metabolic disorders, pulmonary fibrosis, inflammation and
      neurodegenerative diseases. In this review, we provide insights into the
      proteostasis process and how its failure governs neurodegenerative disorders with
      a special focus on Amyotrophic lateral sclerosis (ALS). This article is part of a
      Special Issue entitled SI:ER stress.

PMID- 27033834
TI  - Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and
      challenges.
AB  - The inhaled delivery of nanomedicines can provide a novel, non-invasive
      therapeutic strategy for the more localised treatment of lung-resident diseases
      and potentially also enable the systemic delivery of therapeutics that are
      otherwise administered via injection alone. However, the clinical translation of
      inhalable nanomedicine is being hampered by our lack of understanding about their
      disposition and clearance from the lungs. This review provides a comprehensive
      overview of the biodegradable nanomaterials that are currently being explored as
      inhalable drug delivery systems and our current understanding of their
      disposition within, and clearance from the lungs. The safety of biodegradable
      nanomaterials in the lungs is discussed and latest updates are provided on the
      impact of inflammation on the pulmonary pharmacokinetics of inhaled
      nanomaterials. Overall, the review provides an in-depth and critical assessment
      of the lung clearance mechanisms for inhaled biodegradable nanomedicines and
      highlights the opportunities and challenges for their translation into the
      clinic.

PMID- 27033836
TI  - T1 Mapping in Athletes: A Novel Tool to Differentiate Physiological Adaptation
      From Pathology?

PMID- 27033835
TI  - Athletic Cardiac Adaptation in Males Is a Consequence of Elevated Myocyte Mass.
AB  - BACKGROUND: Cardiac remodeling occurs in response to regular athletic training,
      and the degree of remodeling is associated with fitness. Understanding the
      myocardial structural changes in athlete's heart is important to develop tools
      that differentiate athletic from cardiomyopathic change. We hypothesized that
      athletic left ventricular hypertrophy is a consequence of increased myocardial
      cellular rather than extracellular mass as measured by cardiovascular magnetic
      resonance. METHODS AND RESULTS: Forty-five males (30 athletes and 15 sedentary
      age-matched healthy controls) underwent comprehensive cardiovascular magnetic
      resonance studies, including native and postcontrast T1 mapping for extracellular
      volume calculation. In addition, the 30 athletes performed a maximal exercise
      test to assess aerobic capacity and anaerobic threshold. Participants were
      grouped by athleticism: untrained, low performance, and high performance (O2max
      <60 or>60 mL/kg per min, respectively). In athletes, indexed cellular mass was
      greater in high- than low-performance athletes 60.7+/-7.5 versus 48.6+/-6.3
      g/m(2); P<0.001), whereas extracellular mass was constant (16.3+/-2.2 versus
      15.3+/-2.2 g/m(2); P=0.20). Indexed left ventricular end-diastolic volume and
      mass correlated with O2max (r=0.45, P=0.01; r=0.55, P=0.002) and differed
      significantly by group (P=0.01; P<0.001, respectively). Extracellular volume had
      an inverse correlation with O2max (r=-0.53, P=0.003 and left ventricular mass
      index (r=-0.44, P=0.02). CONCLUSIONS: Increasing left ventricular mass in
      athlete's heart occurs because of an expansion of the cellular compartment while
      the extracellular volume becomes relatively smaller: a difference which becomes
      more marked as left ventricular mass increases. Athletic remodeling, both on a
      macroscopic and cellular level, is associated with the degree of an individual's
      fitness. Cardiovascular magnetic resonance ECV quantification may have a future
      role in differentiating athlete's heart from change secondary to cardiomyopathy.

PMID- 27033837
TI  - Efficiency of locking-plate fixation in isolated talonavicular fusion.
AB  - INTRODUCTION: Talonavicular (TN) fusion is an effective means of treating
      hindfoot deformity and pain. At the cost of a certain limited morbidity, it
      allows lasting stabilization of all of the torque joints. Non-union rates,
      however, are high, due to insufficient mechanical stability of the fixation. The
      present study assessed radiological and clinical results in TN fusion fixed by
      two retrograde compression screws and a dorsal locking plate. MATERIAL AND
      METHOD: A retrospective single-surgeon study recruited 26 TN fusions performed in
      25 patients (13 male, 12 female; mean age, 54.6+/-15.4years) between March 1st,
      2010 and February 28th, 2014. Mean follow-up was 14.9+/-8.7months. Bone fusion
      and anatomic results were assessed on dorsoplantar, lateral and Meary weight
      bearing radiographs. RESULTS: Radiologic fusion was achieved in all cases, at a
      mean 2.7+/-0.7months. Mean TN coverage angle was 21.7+/-10.5 degrees 
      preoperatively and 3.8+/-1.8 degrees  at follow-up. Mean AOFAS score improved
      significantly, from 37.2+/-11.8 (range, 20-53) preoperatively to 79.4+/-11.4
      (range, 45-98) at follow-up. CONCLUSION: TN fusion fixed by two retrograde
      compression screws and a dorsal locking plate provided a high rate of
      consolidation without loss of angular correction and with satisfactory clinical
      results. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective.

PMID- 27033838
TI  - Radiographic outcomes in the coronal plane with iASSISTTM versus optical
      navigation for total knee arthroplasty: A preliminary case-control study.
AB  - BACKGROUND: The new navigation system iASSISTTM for total knee arthroplasty (TKA)
      relies on accelerometers and gyroscopes. The objective of this prospective study
      was to compare the accuracy of iASSISTTM to that of the conventional optical
      navigation system NavitrackTM by determining the rate of mechanical axis
      restoration (+/-3 degrees ), postoperative mean mechanical alignment, rate of
      adequate femoral and tibial component positioning, mean operative time, and
      occurrence of navigation-related adverse events. HYPOTHESIS: The rate of
      mechanical axis restoration (+/-3 degrees ) is not lower with iASSISTTM than with
      the conventional navigation system NavitrackTM. MATERIAL AND METHODS: Of 40
      patients who underwent primary TKA between October 2013 and March 2014, 20 had
      navigation using iASSISTTM and 20 using NavitrackTM. Six months after TKA, an
      independent observer measured three parameters on coronal radiographs: the hip
      knee-ankle angle (HKA), the mechanical lateral distal femoral angle (mLDFA), and
      the mechanical medial proximal tibial angle (mMPTA). RESULTS: The two groups
      showed no significant differences for the rates of HKA restoration (P=0.3),
      adequate coronal positioning of the femoral component (P=0.12) and tibial
      component (P=0.12), or optimal success (P=0.09). Significant differences in
      favour of iASSISTTM were demonstrated for the values and angular deviations of
      the HKA (P=0.02) and mMPTA (P=0.01), whereas no significant difference was found
      for mLDFA. There were no significant differences regarding the mean operative
      time (P=0.06) or the occurrence of navigation-related adverse events (P=0.18).
      DISCUSSION: The iASSISTTM system provides a neutral mechanical axis and optimal
      component position in the coronal plane in 95% of cases, indicating that it is as
      accurate as the optical navigation system NavitrackTM. LEVEL OF EVIDENCE: III,
      prospective case-control study.

PMID- 27033839
TI  - Analysis of risk factors of the postoperative complications of surgical treatment
      of ankle fractures in the elderly: A series of 477 patients.
AB  - INTRODUCTION: The surgical strategy of ankle fractures in elderly subjects is
      controversial because of the high rate of local and general complications. The
      goal of this study was to identify the risk factors of complications of ankle
      fractures in elderly subjects. MATERIALS AND METHODS: Four hundred and seventy
      seven patients operated between 2008 and 2014 were included in this retrospective
      study. The minimum age was 60 years old for women and 70 for men. Patients
      presenting with a pilon fracture or with less than 3 months of follow up were
      excluded. A clinical evaluation of autonomy based on the Parker score and a
      radiographic assessment were performed preoperatively and during follow up The
      characteristics of the fracture, comorbidities and the type of internal fixation
      used were reported. RESULTS: This series included 384 women (81%), mean age 74
      years old (60-99). Most fractures were Weber type B (n=336). Four hundred and
      thirty-one patients (90.4%) received so-called standard internal fixation and 46
      patients (9.6%) received so-called atypical fixation. The rate of general
      complications was 4.6%, and local complications was 23.9%. Univariate analysis of
      the risk factors of general complications identified 2 significant criteria: age
      older than 80 (OR=3.46, P=0.012) and more than 2 comorbidities 2 (OR=10.6,
      P<0.0001). Univariate analysis of risk factors of local complications identified
      2 criteria: an open fracture (OR=4.90, P=0.0016) and age over 80 (OR=1.85,
      P=0.024). Multivariate analysis of risk factors of local complications confirmed
      the relationship with open fractures (OR=4.67, P<0.001). DISCUSSION: The results
      of the management of ankle fractures in elderly subjects is satisfactory. The use
      of standard internal fixation techniques is recommended. The risk of
      complications increases with age, the severity of the fracture and the number of
      associated diseases. LEVEL OF EVIDENCE: Level 4.

PMID- 27033840
TI  - Ankle fractures in the elderly: Treatment and results in 477 patients.
AB  - INTRODUCTION: In the elderly, ankle fractures are likely to cause specific
      complications and have a major impact on their autonomy. The goal of this
      multicentre study was to assess these outcomes in a geriatric population treated
      operatively. MATERIAL AND METHODS: This retrospective study included 477 patients
      with ankle fractures treated surgically between 2008 and 2014. The minimum age
      was 60years for women and 70 for men. Patients with a tibial pilon fracture or
      less than 3months' follow-up were excluded. Functional (autonomy and
      comorbidities) and radiological assessments were performed before surgery and at
      the review. RESULTS: The cohort was 81% female (384 women, 93 men) and had median
      age of 74years. The preoperative autonomy was 7.8 points on average using the
      Parker score. Most of the fractures were either Weber type B (n=336) or type C
      (n=114). At the follow-up, the mean autonomy score was 7.3 points. The fibula was
      fixed with a plate and screws in 69% of cases (n=325), with additional internal
      malleolar fixation was carried out in some cases. A satisfactory result, defined
      as 2 points or less reduction in the Parker score, was found in 89.9% of
      patients; 71.8% had not lost any autonomy. The main risk factors for loss of
      autonomy were being more than 80years of age (OR=2.93, P<0.001), poor surgical
      reduction (OR=2.8, P<0.01), the presence of two or more comorbidities (OR=2.71,
      P<0.001), being female (OR=2.19, P<0.043) or having a Weber type C fracture
      (OR=2.05, P=0.023). DISCUSSION: The functional results are satisfactory overall
      following standard surgical treatment consisting of internal malleolar and
      fibular fixation for ankle fractures in the elderly. We identified five factors
      that greatly impact functional recovery. LEVEL OF EVIDENCE: IV.

PMID- 27033841
TI  - Cross-finger flap for reconstruction of fingertip amputations: Long-term results.
AB  - Fingertip amputations are severe hand injuries. Their treatment must restore the
      sensation and metabolic activity needed for pain-free finger function. The cross
      finger flap (CFF) can be used for this purpose. The goal of this study was to
      assess the long-term clinical outcome following use of this flap. METHODS: This
      was a retrospective analysis of 28 patients operated because of fingertip
      amputation: 16 type 3, 8 type 2 and 4 type 4. The CFF was harvested from an
      adjacent finger on the dorsal side of the middle phalanx down to the epitenon. A
      dorsopalmar hinge was preserved to ensure vascularisation. The CFF was divided an
      average of 18.7 days later. The following parameters were evaluated: pulp volume
      (injured compared to contralateral finger), presence of neuroma, occurrence of
      complications (necrosis, infection, and donor site morbidity), cold discomfort,
      static and tactile discrimination, and patient satisfaction (0 to 10 on VAS).
      RESULTS: The average follow-up was 19.7 years; 22 patients (78.6%) were re
      examined in person or contacted by telephone. The average healthy pulp to
      reconstructed pulp ratio was 1.03. No postoperative complications such as neuroma
      were found. Cold sensitivity was present in 7 patients. The flap was re
      sensitised in all the patients. There was no donor site morbidity. The average
      patient satisfaction score was 9 (range 8-10). CONCLUSIONS: Over the long-term,
      use of the CFF results in nearly normal fingertip metabolism, no complications
      and good distal sensitivity without pain or neuromas. This is a simple, reliable,
      long-lasting reconstruction technique. LEVEL OF EVIDENCE: IV.

PMID- 27033842
TI  - ACL reconstruction in 11 children using the Clocheville surgical technique:
      Objective and subjective evaluation.
AB  - INTRODUCTION: The over-the-top position of the femoral metaphyseal tunnel during
      extraphyseal ligament reconstruction of the anterior cruciate ligament (ACL)
      according to Clocheville may be responsible for negative anisometry. Until now,
      the follow-up of children operated using this pediatric technique was limited to
      screening for iatrogenic epiphysiodesis and the search for postoperative clinical
      instability. The objective of this study was to measure residual laxity using
      objective tests, to quantify muscle recovery, and to evaluate the quality of life
      of these patients in terms of the sports activities. MATERIAL AND METHODS: Eleven
      patients with a mean age of 13.5years were seen at a mean 2.1years of follow-up.
      They underwent objective clinical tests (GNRB((r)) arthrometer and CON-TREX((r))
      dynamometer) as well as subjective questionnaires (IKDC and KOOS). RESULTS: No
      significant difference was found between the healthy knee and the operated knee
      for either the GNRB((r)) at 134N (P=0.79) or at 200N (P=0.98). The CON-TREX((r))
      system allowed us to measure a median percentage of quadriceps recovery of 80.7%
      (range, 52.2-114.5) in terms of muscle power (60 degrees /s) and 81.2% (range,
      51.6-109.6) for muscle response (180 degrees /s). The median subjective IKDC
      score was 94.73/100 (range, 73.68-98.93); 72.7% of the patients resumed
      competitive sports. DISCUSSION: This study's lack of statistical power did not
      show a significant difference in terms of residual laxity at rest of GNRB((r))
      transplants, while a mean differential of +0.4mm was observed. Although pediatric
      transphyseal ligament reconstruction techniques are increasingly used, the
      Clocheville technique remains, in our opinion, an attractive surgical alternative
      in the youngest subjects, with no major risk of iatrogenic epiphysiodesis even
      though it is theoretically anisometric. LEVEL OF EVIDENCE: IV.

PMID- 27033843
TI  - A numerical model to reproduce squeaking of ceramic-on-ceramic total hip
      arthroplasty. Influence of design and material.
AB  - BACKGROUND: Modern ceramic (CoC) bearings for hip arthroplasty (THA) have been
      used in younger patients who expect improved survivorship. However, audible
      squeaking produced by the implant is an annoying complication. Previous numerical
      simulations were not able to accurately reproduce in vitro and in vivo
      observations. Therefore, we developed a finite element model to: (1) reproduce in
      vitro squeaking and validate the model by comparing it with in vivo recordings,
      (2) determine why there are differences between in vivo and in vitro squeaking
      frequencies, (3) identify the stem's role in this squeaking, (4) predict which
      designs and materials are more likely to produce squeaking. HYPOTHESIS: A CoC THA
      numerical model can be developed that reproduces the squeaking frequencies
      observed in vivo. MATERIAL AND METHODS: Numerical methods (finite element
      analysis [ANSYS]) and experimental methods (using a non-lubricated simulated hip
      with a cementless 32mm CoC THA) were developed to reproduce squeaking. Numerical
      analysis was performed to identify the frequencies that cause vibrations
      perceived as an acoustic emission. The finite element analysis (FEA) model was
      enhanced by adjusting periprosthetic bone and soft tissue elements in order to
      reproduce the squeaking frequencies recorded in vivo. A numerical method (complex
      eigenvalue analysis) was used to find the acoustic frequencies of the squeaking
      noise. The frequencies obtained from the model and the hip simulator were
      compared to those recorded in vivo. RESULTS: The numerical results were validated
      by experiments with the laboratory hip simulator. The frequencies obtained (mean
      2790Hz with FEA, 2755Hz with simulator, decreasing to 1759Hz when bone and soft
      tissue were included in the FEA) were consistent with those of squeaking hips
      recorded in vivo (1521Hz). The cup and ceramic insert were the source of the
      vibration, but had little influence on the diffusion of the noise required to
      make the squeaking audible to the human ear. The FEA showed that diffusion of
      squeaking was due to an unstable vibration of the stem during frictional contact.
      The FEA predicted a higher rate of squeaking (at a lower coefficient of friction)
      when TZMFTM alloy is used instead of Ti6Al4V and when an anatomic press-fit stem
      is used instead of straight self-locking designs. DISCUSSION: The current FEA
      model is reliable; it can be used to assess various stem designs and alloys to
      predict the different rates of squeaking that certain stems will likely produce.
      LEVEL OF EVIDENCE: Level IV in vitro study.

PMID- 27033844
TI  - Colitis induced by sodium polystyrene sulfonate in sorbitol: A report of six
      cases.
AB  - Drug-related injury has been noted in virtually all organ systems, and
      recognition of the patterns of injury associated with medication enables
      modification of treatment and reduces the morbidity associated with the side
      effects of drugs. With the large number of new drugs being developed,
      documentation of the morphology of the changes seen as an adverse effect becomes
      important to characterize the pattern of injury. The pathologist is often the
      first to identify these abnormalities and correlate them with a particular drug.
      Kayexalate or sodium polystyrene sulfonate (SPS), a linear polymer derived from
      polystyrene containing sulfonic acid and sulfonate functional groups is used to
      treat hyperkalemia. It is usually administered with an osmotic laxative sorbitol
      orally or as retention enema. This combination has been implicated in causing
      damage to different parts of the gastrointestinal (GI) tract especially the colon
      and causes an established pattern of injury, recognizable by the presence of
      characteristic crystals, is presented to create a greater awareness of the
      Kayexalate colitis. This entity should be included in the differential diagnosis
      of lower GI mucosal injury in a setting of uremia and hyperkalemia. 

PMID- 27033845
TI  - Induced membrane technique for the treatment of bone defects due to post
      traumatic osteomyelitis.
AB  - OBJECTIVES: Induced membrane technique is a relatively new technique in the
      reconstruction of large bone defects. It involves the implantation of
      polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation
      of membranes after radical debridement and reconstruction of bone defects using
      an autologous cancellous bone graft in a span of four to eight weeks. The purpose
      of this study was to explore the clinical outcomes of the induced membrane
      technique for the treatment of post-traumatic osteomyelitis in 32 patients.
      METHODS: A total of 32 cases of post-traumatic osteomyelitis were admitted to our
      department between August 2011 and October 2012. This retrospective study
      included 22 men and ten women, with a mean age of 40 years (19 to 70). Within
      this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to
      12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical
      debridement. After approximately eight weeks, the defects were implanted with
      bone graft. RESULTS: The patients were followed for 27.5 months (24 to 32).
      Radiographic bone union occurred at six months for 26 cases (81%) and clinical
      healing occurred in 29 cases (90%) at ten months. A total of six cases had a
      second debridement before bone grafting because of recurrence of infection and
      one patient required a third debridement. No cases of osteomyelitis had recurred
      at the time of the last follow-up visit. CONCLUSION: The induced membrane
      technique for the treatment of post-traumatic osteomyelitis is a simple, reliable
      method, with good early results. However, there are many challenges in
      determining the scope of the debridement, type of limb fixation and source of
      bone graft to be used.Cite this article: Dr Z. Xie. Induced membrane technique
      for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint
      Res 2016;5:101-105. DOI: 10.1302/2046-3758.53.2000487.

PMID- 27033846
TI  - Pinhole Effect on the Melting Behavior of Ag@Al2O3 SERS Substrates.
AB  - High-temperature surface-enhanced Raman scattering (SERS) sensing is significant
      for practical detections, and pinhole-containing (PC) metal@oxide structures
      possessing both enhanced thermal stability and superior SERS sensitivity are
      served as promising SERS sensors at extreme sensing conditions. Through tuning
      the Al2O3 precursors' exposure time during atomic layer deposition (ALD), Al2O3
      shells with different amount of pinholes were covered over Ag nanorods (Ag NRs).
      By virtue of these unique PC Ag@Al2O3 nanostructures, herein we provide an
      excellent platform to investigate the relationship between the pinhole rate of
      Al2O3 shells and the melting behavior, high-temperature SERS performances of
      these core-shell nanostructures. Pinhole effect on the melting procedures of PC
      Ag@Al2O3 substrates was characterized in situ via their reflectivity variations
      during heating, and the specific melting point was quantitatively estimated. It
      is found that the melting point of PC Ag@Al2O3 raised along with the decrement of
      pinhole rate, and substrates with less pinholes exhibited better thermal
      stability but sacrificed SERS efficiency. This work achieved highly reliable and
      precise control of the pinholes over Al2O3 shells, offering sensitive SERS
      substrates with intensified thermal stability and superior SERS performances at
      extreme sensing conditions. 

PMID- 27033847
TI  - Heating-up Synthesis of MoS2 Nanosheets and Their Electrical Bistability
      Performance.
AB  - Molybdenum disulfide (MoS2) nanosheets were synthesized by using a simple heating
      up approach, in which 1-dodecanethiol (DDT) was used not only as a sulfur source
      but also as the surface ligand. The sheet-like morphology was confirmed by the
      transmission electron microscopy (TEM) and atomic force microscopy (AFM) results,
      and the X-ray diffraction (XRD) patterns and Raman spectrum were employed to
      characterize the structure of the as-synthesized MoS2 nanosheets. The as-obtained
      MoS2 nanosheets blending with a polymer could be used to fabricate an
      electrically bistable device through a simple spin-coating method, and the device
      exhibited an obvious electrical bistability in the I-V curve. The charge
      transport of the device was discussed based on the organic electronic models. 

PMID- 27033848
TI  - Copper Nanoparticle-Incorporated Carbon Fibers as Free-Standing Anodes for
      Lithium-Ion Batteries.
AB  - Copper-incorporated carbon fibers (Cu/CF) as free-standing anodes for lithium-ion
      batteries are prepared by electrospinning technique following with calcination at
      600, 700, and 800  degrees C. The structural properties of materials are
      characterized by X-ray diffraction (XRD), Raman, thermogravimetry (TGA), scanning
      electron microscopy (SEM), transmission electron microscope (TEM), and energy
      dispersive X-ray spectrometry (EDS). It is found that the Cu/CF composites have
      smooth, regular, and long fibrous morphologies with Cu nanoparticles uniformly
      dispersed in the carbon fibers. As free-standing anodes, the unique structural
      Cu/CF composites show stable and high reversible capacities, together with
      remarkable rate and cycling capabilities in Li-ion batteries. The Cu/CF calcined
      at 800  degrees C (Cu/CF-800) has the highest charge/discharge capacities, long
      term stable cycling performance, and excellent rate performance; for instance,
      the Cu/CF-800 anode shows reversible charge/discharge capacities of around 800
      mAh g(-1) at a current density of 100 mA g(-1) with stable cycling performance
      for more than 250 cycles; even when the current density increases to 2 A g(-1),
      the Cu/CF-800 anode can still deliver a capacity of 300 mAh g(-1). This excellent
      electrochemical performance is attributed to the special 1D structure of Cu/CF
      composites, the enhanced electrical conductivity, and more Li(+) active positions
      by Cu nanoinclusion. 

PMID- 27033849
TI  - Creatinine Deiminase Adsorption onto Silicalite-Modified pH-FET for Creation of
      New Creatinine-Sensitive Biosensor.
AB  - In the work, silicalite particles were used for the surface modification of pH
      sensitive field-effect transistors (pH-FETs) with the purpose of developing new
      creatinine-sensitive biosensor. Creatinine deiminase (CD) adsorbed on the surface
      of silicalite-coated pH-FET served as a bioselective membrane. The biosensor
      based on CD immobilized in glutaraldehyde vapor (GA) was taken as control. The
      creatinine-sensitive biosensor obtained by adsorption on silicalite was shown to
      have better analytical characteristics (two- to threefold increased sensitivity
      to creatinine, three- to fourfold lesser response and recovery times, a decrease
      of the detection limit of creatinine determination to 5 MUM, etc.).Additionally,
      the biosensor based on CD adsorbed on silicalite (Sil/CD) was characterized by
      high signal reproducibility (relative standard deviation (RSD) for creatinine
      measurement = 2.6 %) and stability during storage (over 13 months). It was
      experimentally confirmed that the proposed biosensor was not sensitive either to
      high concentrations of sodium chloride or to the macromolecular protein fractions
      and can be used for direct quantitative analysis of creatinine in the blood
      serum.It was concluded that the method of CD adsorption on silicalite is well
      suited for the creation of creatinine-sensitive biosensor with improved working
      characteristics. 

PMID- 27033850
TI  - Sol-Gel Synthesis of Ordered beta-Cyclodextrin-Containing Silicas.
AB  - New approaches for beta-cyclodextrin-containing silicas synthesis were
      demonstrated. Materials with hexagonally ordered mesoporous structure were
      prepared by postsynthesis grafting and by co-condensation methods. beta
      Cyclodextrin activated by a N,N'-carbonyldiimidazole was employed for
      postsynthesis treatment of 3-aminopropyl-modified MCM-41 support as well as for
      sol-gel synthesis with beta-cyclodextrin-containing organosilane and tetraethyl
      orthosilicate participation in the presence of cetyltrimethylammonium bromide.
      The successful incorporation of cyclic oligosaccharide moieties in silica surface
      layer was verified by means of FT-IR spectroscopy and chemical analysis. Obtained
      beta-cyclodextrin-containing materials were characterized by X-ray diffraction,
      transmission electron microscopy, and low-temperature adsorption-desorption of
      nitrogen. In spite of commensurable loading of beta-cyclodextrin groups attained
      by both proposed approaches (up to 0.028 MUmol . m(-2)), it was found that co
      condensation procedure provides uniform distribution of beta-cyclodextrin
      functionalities in silica framework, whereas postsynthesis grafting results in
      modification of external surface of silica surface. Adsorption of benzene from
      aqueous solutions onto the surface of beta-cyclodextrin-containing materials
      prepared by co-condensation method was studied as the function of time and
      equilibrium concentration. Langmuir and Freundlich models were used to evaluate
      adsorption processes and parameters. Adsorption experiments showed that beta
      cyclodextrin-containing silicas could be promising for the trace amount removal
      of aromatics from water. 

PMID- 27033851
TI  - Controllable Growth of Ultrathin P-doped ZnO Nanosheets.
AB  - Ultrathin phosphor (P)-doped ZnO nanosheets with branched nanowires were
      controllably synthesized, and the effects of oxygen and phosphor doping on the
      structural and optical properties were systematically studied. The grown ZnO
      nanosheet exhibits an ultrathin nanoribbon backbone with one-side-aligned
      nanoteeth. For the growth of ultrathin ZnO nanosheets, both oxygen flow rate and
      P doping are essential, by which the morphologies and microstructures can be
      finely tuned. P doping induces strain relaxation to change the growth direction
      of ZnO nanoribbons, and oxygen flow rate promotes the high supersaturation degree
      to facilitate the growth of nanoteeth and widens the nanoribbons. The growth of P
      doped ZnO in this work provides a new progress towards the rational control of
      the morphologies for ZnO nanostructures. 

PMID- 27033852
TI  - The Many Faces of MTA3 Protein in Normal Development and Cancers.
AB  - As a family of chromatin remodeling proteins, metastasis-associated proteins
      (MTAs) have shown to be the master regulators in both physiological and
      pathological contexts. Although MTA3 is the latest being identified in MTA
      family, it has started to draw as much attention as the other family members.
      MTA3 is expressed in various tissues and is associated with different
      physiological functions. In cancerous context, both MTA1 and MTA2 are generally
      considered as oncogenes because they are capable of enhancing metastasis.
      However, MTA3 appears to play more complicated roles in cancers depending on the
      contexts. As a tumor suppressor, MTA3 usually down-regulates Snail, the master
      regulator of epithelium-mesenchymal transition, and subsequently represses cancer
      cell invasion and migration. Additionally, MTA3 may function by enhancing cancer
      cell differentiation without affecting proliferation in certain cancers. On the
      other hand, MTA3 might function in oncogene - related properties similarly as
      MTA1 and MTA2. In this review, we summarize our current understanding about MTA3
      in normal development, cancers as well as other human diseases by comparing the
      similarities and differences between MTA3 and the other members of the MTA
      family.

PMID- 27033853
TI  - Two Defensive Lines in Juvenile Leaf Beetles; Esters of 3-nitropropionic Acid in
      the Hemolymph and Aposematic Warning.
AB  - Juveniles of the leaf beetles in subtribe Chrysomelina have efficient defense
      strategies against predators. When disturbed, they transiently expose volatile
      deterrents in large droplets from nine pairs of defensive glands on their back.
      Here, we report on an additional line of defense consisting of the non-volatile
      isoxazolin-5-one glucoside and its 3-nitropropanoyl ester in the larval
      hemolymph. Because isoxazolin-5-one derivatives were not detectable in related
      leaf beetle taxa, they serve as a diagnostic marker for the Chrysomelina
      subtribe. Conjugation of isotopically labelled 3-nitropropionic acid to
      isoxazolin-5-one glucoside in vivo demonstrates its function as a carrier for the
      3-nitropropanoyl esters. The previous identification of characteristic glucosides
      as precursors of the volatile deterrents underlines the general importance of
      glucosides for sequestration from food plants, and the subsequent transport in
      the hemolymph to the defense system. The combination of repellent volatiles with
      non-volatile toxic compounds in the hemolymph has the potential to create
      synergistic effects since the odorant stimulus may help predators learn to avoid
      some foods. The combination of the two defense lines has the advantage, that the
      hemolymph toxins provide reliable and durable protection, while the repellents
      may vary after a host plant change.

PMID- 27033854
TI  - A scoping review of perineural steroids for the treatment of chronic
      postoperative inguinal pain.
AB  - PURPOSE: To review the literature on the efficacy and safety of perineural
      steroid injections around the ilioinguinal, iliohypogastric, and genitofemoral
      nerves for chronic postoperative inguinal pain (CPIP). METHODS: A scoping review
      was performed to find all relevant case reports, case series, prospective or
      retrospective cohort studies, case-control studies, and randomized controlled
      trials (RCTs) where a steroid was used for perineural procedures around
      ilioinguinal, iliohypogastric, and/or genitofemoral nerves for CPIP. Databases
      searched included Ovid MEDLINE, EMBASE, CINHAL, Cochrane CENTRAL, and Google
      Scholar. RESULTS: A total of five publications were found-three studies were
      prospective case series, one a retrospective cohort study, and one a RCT. The
      most common steroids used were methylprednisolone and triamcinolone. The average
      methylprednisolone-equivalent dose used per procedure was 46 mg (SD 21.9).
      Procedural guidance included anatomic landmarks (three studies), nerve
      stimulation and ultrasound (one study), and computed tomography guidance (one
      study). Four studies reported analgesic benefit in 55-75 % of included patients,
      with one study documenting an effect up to 50 months later after steroid
      perineural injections. The RCT demonstrated no benefit of adding steroid to a
      local anesthetic in the perioperative setting but it did not enroll patients with
      existing neuropathic pain. No adverse outcomes of perineural steroids were
      documented within reviewed studies. CONCLUSIONS: The paucity of data,
      heterogeneity and lack of appropriate control groups in the available literature
      precludes firm conclusions on the efficacy and safety of perineural steroids for
      CPIP. Future adequately powered, high-quality, placebo-controlled studies are
      needed.

PMID- 27033855
TI  - Juvenile roach (Rutilus rutilus) increase their anaerobic metabolism in response
      to copper exposure in laboratory conditions.
AB  - This study aims to determine the potential impairment of cell energy synthesis
      processes (glycolysis and respiratory chain pathways) by copper in juvenile roach
      at different regulation levels by using a multi-marker approach. Juvenile roach
      were exposed to 0, 10, 50, and 100 ug/L of copper for 7 days in laboratory
      conditions. The glycolysis pathway was assessed by measuring the relative
      expression levels of 4 genes encoding glycolysis enzymes. The respiratory chain
      was studied by assessing the electron transport system and cytochrome c oxidase
      gene expression. Muscle mitochondria ultrastructure was studied, and antioxidant
      responses were measured. Furthermore, the main energy reserves-carbohydrates,
      lipids, and proteins-were measured, and cellular energy was evaluated by
      measuring ATP, ADP, AMP and IMP concentrations. This study revealed a disturbance
      of the cell energy metabolism due to copper exposure, with a significant decrease
      in adenylate energy charge in roach exposed to 10 MUg/L of copper after 1 day.
      Moreover, ATP concentrations significantly decreased in roach exposed to 10 MUg/L
      of copper after 1 day. This significant decrease persisted in roach exposed to 50
      ug/L of copper after 7 days. AMP concentrations increased in all contaminated
      fish after 1 day of exposure. In parallel, the relative expression of 3 genes
      encoding for glycolysis enzymes increased in all contaminated fish after 1 day of
      copper exposure. Focusing on the respiratory chain, cytochrome c oxidase gene
      expression also increased in all contaminated fish at the two time-points. The
      activity of the electron transport system was not disturbed by copper, except in
      roach exposed to 100 ug/L of copper after 1 day. Copper induced a metabolic
      stress. Juvenile roach seemed to respond to the ensuing high energy demand by
      increasing their anaerobic metabolism, but the energy produced by the anaerobic
      metabolism is unable to compensate for the stress induced by copper after 7 days.
      This multi-marker approach allows us to reach a greater understanding of the
      effects of copper on the physiological responses of juvenile roach. 

PMID- 27033856
TI  - Accumulation of heavy metals and antioxidant responses in Pinus sylvestris L.
      needles in polluted and non-polluted sites.
AB  - The purpose of this study was to determine the concentrations of heavy metals
      (cadmium, iron, manganese, lead and zinc) in current-year, 1-year old and 2-year
      old needles of Pinus sylvestris L. Trees were from three heavily polluted
      (immediate vicinity of zinc smelter, iron smelter and power plant) and three
      relatively clean sites (nature reserve, ecologically clean site and unprotected
      natural forest community) in southern Poland. Analysis also concerned the
      antioxidant response and contents of protein, proline, total glutathione, non
      protein thiols and activity of guaiacol peroxidase (GPX) in the needles.
      Generally, in pine needles from the polluted sites, the concentrations of the
      metals were higher and increased with the age of needles, and in most cases,
      antioxidant responses also were elevated. The highest levels of Cd, Pb and Zn
      were found in 2-year old pine needles collected near the polluted zinc smelter
      (respectively: 6.15, 256.49, 393.5 mg kg(-1)), Fe in 2-year old pine needles in
      the vicinity of the iron smelter (206.82 mg kg(-1)) and Mn in 2-year old needles
      at the ecologically clean site (180.32 mg kg(-1)). Positive correlations were
      found between Fe, Mn and Pb and the content of proteins and NPTs, between Cd and
      non-protein -SH groups, and between Zn and proline levels. The activity of GPX
      increased under the influence of Mn, while glutathione levels tended to decrease
      as Mn levels rose. The data obtained show that the levels of protein and non
      protein -SH groups may be useful in biological monitoring, and that these
      ecophysiological parameters seem to be good evidence of elevated oxidative stress
      caused by heavy metals. 

PMID- 27033857
TI  - Stackable and submergible microbial fuel cell modules for wastewater treatment.
AB  - The stackable and submergible microbial fuel cell (SS-MFC) system was fabricated
      consisting of three MFC modules (#1, #2 and #3) that were immersed in an
      anaerobic tank as a 30 L anode compartment. Each module consisted of the anion
      exchange membrane-membrane electrode assembly (A-MEA) and cation exchange
      membrane-MEA (C-MEA). Two MEAs shared a cathode compartment in the module and the
      three modules shared a anode compartment The SS-MFC system was operated with two
      phase. After batch feeding (phase I), the system was operated under continuous
      mode (phase II) with different organic concentrations (from 50 to 1000 mg/L) and
      different hydraulic retention times (HRT; from 3.4 to 7.2 h). The SS-MFC system
      successfully produced a stable voltage. A-MEA generated a lower power density
      than the C-MEA because of the former's high activation and resistance loss. C-MEA
      showed a higher average maximum power density (3.16 W/m(3)) than A-MEA (2.82
      W/m(3)) at 70 mL/min (HRT of 7.2 h). The current density increased as the organic
      concentration was increased from 70 to 1000 mg/L in a manner consistent with
      Monod kinetics. When the HRT was increased from 3.4 to 7.2 h, the power densities
      of the C-MEAs increased from 34.3-40.9 to 40.7-45.7 mW/m(2), but those of the A
      MEAs decreased from 25.3-48.0 to 27.7-40.9 mW/m(2). Although power generation was
      affected by HRT, organic concentrations, and separator types, the proposed SS-MFC
      modules can be applied to existing wastewater treatment plants. 

PMID- 27033858
TI  - Performances of low-dose dual-energy CT in reducing artifacts from implanted
      metallic orthopedic devices.
AB  - OBJECTIVES: The objective was to evaluate the performances of dose-reduced dual
      energy computed tomography (DECT) in decreasing metallic artifacts from
      orthopedic devices compared with dose-neutral DECT, dose-neutral single-energy
      computed tomography (SECT), and dose-reduced SECT. MATERIALS AND METHODS: Thirty
      implants in 20 consecutive cadavers underwent both SECT and DECT at three fixed
      CT dose indexes (CTDI): 20.0, 10.0, and 5.0 mGy. Extrapolated monoenergetic DECT
      images at 64, 69, 88, 105, 120, and 130 keV, and individually adjusted monoenergy
      for optimized image quality (OPTkeV) were generated. In each group, the image
      quality of the seven monoenergetic images and of the SECT image was assessed
      qualitatively and quantitatively by visually rating and by measuring the maximum
      streak artifact respectively. RESULTS: The comparison between SECT and OPTkeV
      evaluated overall within all groups showed a significant difference (p <0.001),
      with OPTkeV images providing better images. Comparing OPTkeV with the other DECT
      images, a significant difference was shown (p <0.001), with OPTkeV and 130-keV
      images providing the qualitatively best results. The OPTkeV images of 5.0-mGy
      acquisitions provided percentages of images with scores 1 and 2 of 36 % and 30 %
      respectively, compared with 0 % and 33.3 % of the corresponding SECT images of 10
      and 20-mGy acquisitions. Moreover, DECT reconstructions at the OPTkeV of the low
      dose group showed higher CT numbers than the SECT images of dose groups 1 and 2.
      CONCLUSIONS: This study demonstrates that low-dose DECT permits a reduction of
      artifacts due to metallic implants to be obtained in a similar manner to neutral
      dose DECT and better than reduced or neutral-dose SECT.

PMID- 27033859
TI  - External validity of the "all-comers" design: insights from the BIOSCIENCE trial.
AB  - OBJECTIVES: We sought to systematically evaluate the external validity of a
      contemporary randomized controlled stent trial (BIOSCIENCE). METHODS: Baseline
      characteristics and clinical outcomes of patients enrolled into the BIOSCIENCE
      trial at Bern University Hospital (n = 1216) were compared to those of patients
      included in the CARDIOBASE Bern PCI Registry at the same institution (n = 1045).
      The primary study endpoint was the rate of target lesion failure (TLF), defined
      as a composite of cardiac death, target vessel-myocardial infarction (MI) or
      target lesion revascularization (TLR), at 1 year. RESULTS: Women were
      underrepresented in the RCT compared to the registry (25 vs. 29.4 %, p = 0.020).
      Non-participants were older compared to study participants (69.2 +/- 12.4 vs.
      67.0 +/- 11.6, p < 0.001), and had a higher prevalence of previous
      cerebrovascular events (10.8 vs. 5.2 %, p < 0.001), and chronic renal failure
      (35.5 vs. 15.6 %, p < 0.001). ST-segment elevation myocardial infarction (STEMI)
      and Killip class IV at presentation were more common among non-participants than
      participants (30.7 vs. 21.1 %, p < 0.001 and 7.8 vs. 0.4 %, p < 0.001,
      respectively). At 1 year, non-participants experienced a significantly higher
      rate of TLF, (15.0 vs. 6.5 %, p < 0.001), and patient-oriented composite endpoint
      (POCE), including death, MI or any repeat revascularization (21.6 vs. 11.2 %, p <
      0.001). There was a significant interaction between POCE and presence or absence
      of an acute coronary syndrome in participants versus non-participants,
      respectively (p = 0.009). CONCLUSIONS: Non-participants of this all-comers trial
      had a higher risk profile and adverse prognosis compared to study participants.
      Further efforts are needed to improve the external validity of contemporary RCTs.

PMID- 27033860
TI  - Percutaneously Assisted "Two-Ports" Transperitoneal Radical Nephrectomy: Initial
      Series.
AB  - Looking for a virtually "scarless" surgery mini-laparoscopy (ML) could be a
      viable alternative to conventional laparoscopy. ML is a reproducible technique
      and allows for the preservation of the triangulation concept, the cornerstone of
      laparoscopic surgery. Drawback of ML could be the poor performance of
      miniaturized instruments that could affect the confidence of the surgeon and
      limit the indications. The recent availability of a novel mini-laparoscopic
      platform in our center expanded the indications of ML to radical nephrectomy even
      in cases of large renal tumors in kidneys with abundant perirenal fat. The
      platform is composed by mini-instruments with the peculiarity of a 2.9-mm shaft
      that is mounted on a handle and a jaw that are comparable in size and performance
      to those of conventional instruments, increasing the ergonomy and the confidence
      perceived by the surgeon. Allowing for inclusion criteria, nine consecutive
      patients were enrolled in our prospective study and underwent percutaneously
      assisted "two-ports" radical nephrectomy. Preliminary data showed that the novel
      platform allowed us to perform a safe and effective procedure with acceptable
      perioperative outcomes and apparent improvements in cosmesis. Larger sample size
      and comparative studies are needed to confirm these findings.

PMID- 27033861
TI  - Impact of laboratory cost display on resident attitudes and knowledge about
      costs.
AB  - AIM: Cost awareness has been proposed as a strategy for curbing the continued
      rise of healthcare costs. However, most physicians are unaware of the cost of
      diagnostic tests, and interventions have had mixed results. We sought to assess
      resident physician cost awareness following sustained visual display of costs
      into electronic health record (EHR) order entry screens. STUDY DESIGN: We
      completed a preintervention and postintervention web-based survey. Participants
      were physicians in internal medicine, paediatrics, combined medicine and
      paediatrics, obstetrics and gynaecology, emergency medicine, and orthopaedic
      surgery at one tertiary co are academic medical centre. Costs were displayed in
      the EHR for 1032 unique laboratory orders. We measured attitudes towards costs
      and estimates of Medicare reimbursement rates for 11 common laboratory and
      imaging tests. RESULTS: We received 209 survey responses during the
      preintervention period (response rate 71.1%) and 194 responses during the
      postintervention period (response rate 66.0%). The proportion of residents that
      agreed/strongly agreed that they knew the costs of tests they ordered increased
      after the cost display (8.6% vs 38.2%; p<0.001). Cost estimation accuracy among
      residents increased after the cost display from 24.0% to 52.4% for laboratory
      orders (p<0.001) and from 37.7% to 49.6% for imaging orders (p<0.001).
      CONCLUSIONS: Resident cost awareness and ability to accurately estimate
      laboratory order costs improved significantly after implementation of a
      comprehensive EHR cost display for all laboratory orders. The improvement in cost
      estimation accuracy for imaging orders, which did not have costs displayed,
      suggested a possible spillover effect generated by providing a cost context for
      residents.

PMID- 27033862
TI  - General practitioners' perspectives on the management of gout: a qualitative
      study.
AB  - BACKGROUND: Many quantitative studies globally have identified suboptimal
      management of gout. PURPOSE: To explore management of gout from the perspective
      of general practitioners (GPs), while identifying the barriers and possible
      strategies for improvement. STUDY DESIGN: This descriptive qualitative study used
      semistructured interviews with 14 purposely selected GPs from four separate
      general practices in Townsville. The questions focused on management strategies,
      practicalities in managing gout, barriers and possible strategies to improve
      management. RESULTS: Indomethacin was commonly reported to be used in acute gout
      with progression to allopurinol after the acute stage had subsided. There were
      differences with the initial allopurinol dose and follow-up periods. GPs reported
      lack of patient adherence to allopurinol and lifestyle modifications, mainly due
      to lack of education. Most suggested the need for allied health input and
      improved patient education. CONCLUSIONS: Tailor-made plan in terms of education
      and lifestyle advice could help adherence to gout management.

PMID- 27033863
TI  - Relearning the importance of routines from rugby player Goromaru.

PMID- 27033864
TI  - Assessment of a needle-tracking system for bipolar radiofrequency ablation.
AB  - PURPOSE: The purpose of this study was to assess the accuracy and efficacy of a
      needle-tracking system in phantom and clinical studies using bipolar electrodes.
      METHODS: To observe the tip of the electrode, a needle-tracking system with a
      volume navigation system was used. In the phantom study, the electrode was
      inserted at various angles and the error was verified. In the clinical study, 21
      nodules close to extrahepatic organs or major vessels were enrolled between May
      and October 2014. After puncturing with the needle-tracking system, computed
      tomography (CT) was performed. The distances between the electrode tip and
      extrahepatic organs or major vessels were measured on both B-mode ultrasound (US)
      and CT. By comparing these distances, the accuracy of this system was evaluated.
      RESULTS: In the phantom study, the deviation between the tip of the electrode and
      the virtual tip of the electrode was analyzed. The median values were within 2 mm
      at each puncture angle. In the clinical study, the difference between B-mode US
      and CT was less (mean value 1.17 +/- 1.76 mm; range 0-3.5 mm). CONCLUSION: The
      needle-tracking system is an accurate and useful system for bipolar
      radiofrequency ablation.

PMID- 27033865
TI  - Contrast-enhanced ultrasonography with Sonazoid for diagnosis of gangrenous
      cholecystitis.
AB  - PURPOSE: This prospective study investigated the ability of contrast-enhanced
      ultrasonography (CEUS) with Sonazoid to diagnose gangrenous cholecystitis and
      determined the inter-observer agreement. METHODS: From September 2012 to August
      2014, 27 patients with acute cholecystitis underwent preoperative CEUS
      (registration number 1277). After Sonazoid injection, harmonic imaging of the
      gallbladder wall was performed, and the findings were recorded using movie clips.
      The signal intensity was classified as absence (uncomplicated) or presence of
      perfusion defects (gangrenous). The physician performing CEUS recorded the
      findings immediately after the examination. Another physician (blinded to the
      clinical information) then reviewed the movie clips and recorded the findings.
      The final diagnosis was determined by histological examination in all 27
      patients. RESULTS: The final diagnosis was gangrenous cholecystitis in 15
      patients and uncomplicated cholecystitis in 12. On CEUS examination, perfusion
      defects were detected in 10 patients with gangrenous cholecystitis, giving a
      sensitivity of 66.7 %, specificity of 100 %, positive predictive value of 100 %,
      and negative predictive value of 70.6 %. On review of the movie clips, these
      values were 73.3, 100, 100, and 75.0 %, respectively. The inter-observer
      agreement between physicians was good (kappa coefficient, 0.64). CONCLUSIONS:
      CEUS with Sonazoid is a useful and reproducible modality for diagnosing
      gangrenous cholecystitis.

PMID- 27033866
TI  - Discordance between conventional ultrasonography and ElastPQ for assessing
      hepatic fibrosis in chronic hepatitis B: frequency and independent factors.
AB  - PURPOSE: To investigate the frequency of discordance and to identify factors
      associated with discordance between ultrasonographic and elastographic grades for
      assessing hepatic fibrosis in Asian patients with chronic hepatitis B. METHODS:
      Three hundred thirty-four patients with chronic hepatitis B for which both
      conventional ultrasonography and liver stiffness measurements using elastography
      were available were included. Patients were graded as 'normal', 'chronic liver
      disease', or 'liver cirrhosis' by ultrasonography, and as 'no significant
      fibrosis', 'significant fibrosis', or 'liver cirrhosis' by elastography, and the
      results of these two modalities were compared. Logistic regression analyses were
      performed to identify independent factors associated with discordant results.
      RESULTS: Of the 334 patients, 153 (45.8 %), 115 (34.4 %), and 66 (19.8 %)
      patients were 'normal', 'chronic liver disease', and 'liver cirrhosis',
      respectively, based on the ultrasonographic grades, and 290 (86.8 %), 29 (8.7 %),
      and 15 (4.5 %) patients were 'no significant fibrosis,' 'significant fibrosis',
      and 'liver cirrhosis', respectively, based on the elastographic values. Among
      them, 173 (51.8 %) showed discordance with respect to severity of hepatic
      fibrosis. In multivariable analysis, discordance was more frequent in patients
      with ultrasonographic grades of 'chronic liver disease' [adjusted odds ratio
      (AOR), 1924; P < 0.001] and 'liver cirrhosis' (AOR, 4498; P < 0.001), whereas
      patients with an elastographic grade of 'liver cirrhosis' showed a negative
      association with discordance (AOR, 0.002; P = 0.007). CONCLUSION: There was a
      high rate of discordance between hepatic fibrosis grades determined by
      ultrasonography and elastography. Considering the accuracy of liver stiffness
      evaluation by elastography, conventional ultrasonography might overestimate
      hepatic fibrosis in chronic hepatitis B.

PMID- 27033867
TI  - Low mechanical index contrast mode versus high mechanical index contrast mode:
      which is a more sensitive method for detecting Sonazoid microbubbles in the liver
      of normal subjects?
AB  - PURPOSE: Using the low mechanical index (MI) contrast mode and the high MI
      contrast mode of contrast-enhanced ultrasonography, we evaluated which method is
      more sensitive for detecting Sonazoid microbubbles in the liver of normal
      subjects. METHODS: Thirteen normal subjects received an intravenous bolus
      injection of 0.2 mL of Sonazoid. We defined the intensity difference as the
      intensity post-injection minus the intensity pre-injection. We evaluated the
      intensity difference at the portal vein using both the low MI (0.21-0.23) and the
      high MI (0.7-1.2) at 1 min, at every 10 min between 10 to 60 min, and at every 30
      min between 60 to 300 min post-injection. The intensity difference at the liver
      parenchyma was also evaluated at eight points (1, 10, 30, 60, 120, 180, 240, and
      300 min) using the low MI and at three points (1, 10, and 300 min) using the high
      MI. RESULTS: The intensity differences at the portal vein measured using high MI
      were significantly higher than those measured using the low MI at each point
      between 1 and 240 min (P < 0.01) and at 270 min post-injection (P < 0.05). The
      intensity differences at the liver parenchyma measured using the high MI were
      also significantly higher than those measured using the low MI at each time point
      (P < 0.01). CONCLUSION: Compared with the low MI, the high MI is more sensitive
      for detecting Sonazoid microbubbles in the liver of normal subjects.

PMID- 27033868
TI  - Changes in uterine flexion caused by cesarean section: correlation between post
      flexion and deficient cesarean section scars.
AB  - PURPOSE: To investigate changes in uterine flexion after cesarean delivery in
      comparison with vaginal delivery, and their relationship with the presence of
      deficient cesarean section scars. METHODS: In 147 women who had a vaginal
      delivery and 101 women who had a cesarean delivery, transvaginal ultrasonographic
      photographs of the uterus were obtained at the first trimester of pregnancy and
      at 1 month postpartum, and they were reviewed to determine changes in uterine
      flexion. The presence of a deficient cesarean section scar was also reviewed in
      women with a cesarean section. RESULTS: Changes in uterine flexion were observed
      more frequently among the woman with a cesarean delivery than in those with a
      vaginal delivery. The incidence of post-flexed uterus during puerperium tended to
      increase depending on the number of cesarean sections the woman had undergone. In
      the women with a cesarean section, changes in uterine flexion were more
      frequently observed in the women with a deficient cesarean section scar than in
      those without one. CONCLUSION: Changes in uterine flexion after birth occurred
      more frequently in the women who had a cesarean delivery than in those who had a
      vaginal delivery, especially in the presence of a deficient cesarean section
      scar.

PMID- 27033869
TI  - Prediction of spontaneous vaginal delivery by transperineal ultrasound performed
      just after full cervical dilatation is determined.
AB  - PURPOSE: To investigate whether transperineal ultrasound examination just after
      full cervical dilatation is determined can predict the mode of delivery. METHODS:
      This was a prospective observational study of pregnant women. After full cervical
      dilatation was determined by vaginal examination during labor, transperineal
      ultrasound was immediately performed, and the head direction (HD), progression
      distance (PD), and angle of progression (AoP) were measured. The cases were
      divided into two groups: spontaneous vaginal delivery and operative delivery due
      to failure of progression. Differences between the groups were statistically
      analyzed using Student's t test and Fisher's exact test. RESULTS: Of the 50
      women, 42 had spontaneous vaginal deliveries and 8 had vacuum extractions. The
      spontaneous delivery group had significantly higher HD, PD, and AoP values than
      the vacuum extraction group. The areas under the receiver-operating
      characteristic curves for the prediction of spontaneous vaginal delivery were
      0.850 for HD, 0.827 for PD, and 0.783 for AoP. The optimum cut-off points and
      positive predictive values were 83 degrees  and 92.9 % for HD, 56 mm and 94.9 %
      for PD, and 146 degrees  and 94.3 % for AoP, respectively. CONCLUSION:
      Transperineal ultrasound examination just after full cervical dilatation was
      determined was useful in predicting spontaneous vaginal delivery.

PMID- 27033870
TI  - Associations between increased renal resistive index and cardiovascular events.
AB  - BACKGROUND AND PURPOSE: Chronic kidney disease is a risk factor for
      cardiovascular disease (CVD). Renal resistive index (RI) measured by Doppler
      ultrasonography is associated with renal impairment. We investigated the
      relationship between RI and cardiac function, and evaluated the utility of RI for
      predicting cardiac events in patients with CVD. METHODS AND RESULTS: Renal
      Doppler ultrasonography and echocardiography were performed in a total of 452
      patients with CVD. Correlations of RI with serum creatinine and estimated
      glomerular filtration rate (eGFR) were significant but not strong (r = 0.37, p <
      0.001; r = -0.42, p < 0.001, respectively). RI correlated positively with age,
      left atrial volume index, left ventricular mass index, and early transmitral
      velocity to mitral annular early diastolic velocity (e') ratio (E/e'), and showed
      significant negative correlations with e' and diastolic blood pressure. Between
      two subgroups-112 patients hospitalized with cardiovascular events (Group A) and
      200 age- and eGFR-matched controls (Group B)-RI was significantly higher in Group
      A than in Group B, although age and eGFR were similar. CONCLUSIONS: RI reflects
      the impairment of intrarenal hemodynamics that cannot be adequately elucidated by
      eGFR alone. Assessment of renal RI may be useful in conjunction with prognostic
      estimates for patients with CVD.

PMID- 27033871
TI  - Two cases of immunoglobulin G4-related sclerosing cholangitis in which
      transabdominal ultrasonography was useful in diagnosis and follow-up observation.
AB  - Immunoglobulin G4-related disease (IgG4-RD) represents a group of disorders that
      share features of inflammation, plasma cell infiltrates, and fibrosis. Sclerosing
      cholangitis is a disorder involving inflammation, scarring, and destruction of
      the bile ducts. IgG4-related sclerosing cholangitis (IgG4-SC) has been proposed
      as a bile duct lesion associated with IgG4-RD. This disease entity can be
      distinguished from other types of sclerosing cholangitis and classified into four
      types based upon the region of strictures revealed by cholangiography. Here, we
      present two cases in which the finding of bile duct wall thickening visualized
      with transabdominal ultrasonography was useful in the diagnosis of patients with
      IgG4-SC. At present, transabdominal ultrasonography is not included in the
      diagnostic algorithm for IgG4-SC. We are certain that detailed observation of the
      bile duct wall with transabdominal ultrasonography can make a significant
      contribution to the diagnosis of IgG4-SC. Furthermore, we propose that
      transabdominal ultrasonography may be useful in following clinical improvement in
      cases where a steroid trial is the best option for treatment. Both cases
      emphasize the practicality of transabdominal ultrasonography in the diagnosis and
      follow-up observation of IgG4-SC. 

PMID- 27033872
TI  - High-intensity focused ultrasound treatment for intra-abdominal desmoid tumors: a
      report of four cases.
AB  - Desmoid tumors are rare clonal fibroblastic proliferations that can arise at
      abdominal or extra-abdominal sites. Complete surgical resection is the primary
      treatment for resectable desmoid tumors, but a high rate of local recurrence has
      been reported even after complete resection. For patients with a recurrent tumor,
      the goals of treatment are to control the recurrence, maintain quality of life,
      and prolong survival. Radiofrequency ablation, radiotherapy, chemotherapy, and
      other medical therapies can be used as alternative methods, but there are
      considerable controversies over the roles of these methods in the management of
      desmoid tumors. High-intensity focused ultrasound (HIFU) is a minimally invasive
      and effective method for treatment of solid tumors. We used HIFU to treat four
      patients with intra-abdominal desmoid tumors from June 2011 to September 2013.
      Post-procedural pain was seen in all patients. One patient had an intra-abdominal
      abscess and another suffered a slight injury to the femoral nerve. The patients
      were followed up for 19-46 months (mean 34 months) until April 2015. The tumor in
      one patient disappeared, and no tumor progression was observed in the other
      patients.

PMID- 27033873
TI  - Ultrasonographic characteristics of congenital corneal staphyloma.
AB  - This case report describes the ultrasonographic characteristics of congenital
      corneal staphyloma (CCS) in a neonate on the birth day, with a massively
      staphylomatous and ectatic left cornea, which was forward protrusive between the
      eyelids. Ultrasound biomicroscopy (UBM) revealed the cornea of the left eye as
      thin and ectatic, with an irregular contour and unidentified layers. The anterior
      chamber was extraordinarily deep. Apart from histology, UBM can be used for
      understanding the microstructure of the anterior ocular segment, which may
      directly guide the diagnosis of CCS in a timely manner.

PMID- 27033874
TI  - Effectiveness of the Young-Laplace equation at nanoscale.
AB  - Using molecular dynamics (MD) simulations, a new approach based on the behavior
      of pressurized water out of a nanopore (1.3-2.7 nm) in a flat plate is developed
      to calculate the relationship between the water surface curvature and the
      pressure difference across water surface. It is found that the water surface
      curvature is inversely proportional to the pressure difference across surface at
      nanoscale, and this relationship will be effective for different pore size,
      temperature, and even for electrolyte solutions. Based on the present results, we
      cannot only effectively determine the surface tension of water and the effects of
      temperature or electrolyte ions on the surface tension, but also show that the
      Young-Laplace (Y-L) equation is valid at nanoscale. In addition, the contact
      angle of water with the hydrophilic material can be further calculated by the
      relationship between the critical instable pressure of water surface (burst
      pressure) and nanopore size. Combining with the infiltration behavior of water
      into hydrophobic microchannels, the contact angle of water at nanoscale can be
      more accurately determined by measuring the critical pressure causing the
      instability of water surface, based on which the uncertainty of measuring the
      contact angle of water at nanoscale is highly reduced. 

PMID- 27033875
TI  - Blood and guts: a case of early childhood Crohn's disease.

PMID- 27033876
TI  - Nutrition Assistance Programs: Cause or Solution to Obesity.
AB  - Three nutrition assistance programs-Supplemental Nutrition Assistance Program
      (SNAP), Special Nutrition Program for Women, Infants and Children (WIC), and
      National School Lunch Program (NSLP)-serve as the backbone of the nutrition
      safety net in the USA. These programs have been successful in achieving many of
      their initial goals of improving food purchases, food intake, and/or nutritional
      status of low-income, vulnerable Americans. The emphasis in these programs has
      now broadened to also include an obesity prevention focus. Recent changes in
      program components demonstrate the revised objectives of the program. SNAP, WIC,
      and NSLP increase economic access to an adequate diet but access alone is
      unlikely to be the total solution to obesity prevention. An ecological approach,
      incorporating the nutrition programs, appears to be a more promising strategy to
      leverage the impact of SNAP, WIC, and NSLP. 

PMID- 27033877
TI  - Obesity Prevention in the Nordic Countries.
AB  - Previous studies have shown that mean BMI and prevalences of overweight/obesity
      and obesity have increased over the last decades in the Nordic countries, despite
      highly regulated societies with a focus on obesity prevention. We review recent
      overweight/obesity and obesity prevention initiatives within four of the five
      Nordic countries: Sweden, Denmark, Finland, and Iceland. Moreover, we analyze the
      current situation based on monitoring data on BMI collected in 2011 and 2014, and
      obtain overall estimates of overweight/obesity and obesity prevalences for the
      Nordic Region. Data analysis shows that obesity in adults has increased from 2011
      to 2014, while no significant changes were found for children. No significant
      increases were found for mean BMI and overweight/obesity prevalence. Obesity
      prevention initiatives among the Nordic countries are highly similar although
      minor differences are present, which is rooted in transnational Nordic
      cooperation and comparable societal structures. 

PMID- 27033878
TI  - Characteristics of Clostridium difficile infection in patients with discordant
      diagnostic test results.
AB  - BACKGROUND: Clinical features of Clostridium difficile infection (CDI) cases
      diagnosed by detection of polymerase chain reaction (PCR), with negative toxin
      enzyme immunoassay results (EIA) have not been fully elucidated. The purpose of
      this study was to determine the magnitude of CDI patients who had negative EIA
      toxin determinations but positive PCR tests, and their differences in clinical
      presentation. METHODS: We performed a retrospective study comparing the clinical
      features of CDI cases detected by EIA (toxins A + B) with cases detected by PCR
      (toxin negative, PCR positive) over a 16-month period. Only patients with an
      initial Clostridium difficile infection episode that fulfilled a standardized
      definition were included. RESULTS: During the study period, 107 episodes of CDI
      were detected. Seventy-four patients (69%) had positive glutamate dehydrogenase
      (GDH) antigen and EIA determinations (EIA positive patients). Thirty-three
      patients (31%) had GDH positive, negative toxin EIA and positive PCR
      determination (PCR positive patients). PCR positive patients were younger, 57
      (27) years (mean [SD]), than EIA positive patients, 71 (16) years, (p < 0.001).
      Fewer PCR positive patients were receiving proton pump inhibitors (21 patients,
      64%) than EIA positive patients (61 patients, 82%, p = 0.034). The clinical
      presentation was similar in both groups. In the multivariate analysis, lower age
      was identified as the only independent variable associated with PCR positive
      patients. CONCLUSIONS: One third of Clostridium difficile infection patients
      present negative toxin EIA and PCR positive tests. Performing PCR determination
      after the negative EIA test is more relevant in younger patients.

PMID- 27033879
TI  - The effects of forest therapy on depression and anxiety in patients with chronic
      stroke.
AB  - OBJECTIVE: To assess whether forest therapy is effective for treating depression
      and anxiety in patients with chronic stroke by using several psychological tests.
      We measured reactive oxygen metabolite (d-ROM) levels and biological antioxidant
      potentials (BAPs) associated with psychological stress. METHODS: Fifty-nine
      patients with chronic stroke were randomly assigned to either a forest group
      (staying at a recreational forest site) or to an urban group (staying in an urban
      hotel); the duration and activities performed by both groups were the same.
      Scores on the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale
      (HAM-D17), Spielberger State-Trait Anxiety Inventory (STAI), d-ROMs and BAPs were
      evaluated both before and after the treatment programs. RESULTS: In the forest
      group, BDI, HAM-D17 and STAI scores were significantly lower following treatment,
      and BAPs were significantly higher than baseline. In the urban group, STAI scores
      were significantly higher following treatment. Moreover, BDI, HAM-D17 and STAI
      scores of the forest group were significantly lower, and BAPs were significantly
      higher following treatment (ANCOVA, p <0.05). CONCLUSION: Forest therapy is
      beneficial for treating depression and anxiety symptoms in patients with chronic
      stroke, and may be particularly useful in patients who cannot be treated with
      standard pharmacological or electroconvulsive therapies.

PMID- 27033880
TI  - ADHD Is Highly Prevalent in Patients Seeking Treatment for Cannabis Use
      Disorders.
AB  - OBJECTIVE: To estimate the prevalence of ADHD and determine an effective
      screening test for ADHD in a population-seeking treatment for cannabis use
      disorders. METHOD: The Conners Adult ADHD Diagnostic Interview forDiagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV; CAADID) was used
      to generate sensitivity and specificity data for ADHD screening tests, which were
      then administered to 99 participants seeking treatment for cannabis use disorders
      to estimate ADHD prevalence. RESULTS: The prevalence estimated from the Wender
      Utah Rating Scale (WURS) was 45% (sensitivity = 0.88, sensitivity of 0.75), from
      the Conners Adult ADHD Rating Scale (CAARS) 34% (sensitivity = 0.80, specificity
      = 0.91), from the WURS + CAARS 36% (sensitivity = 0.71, specificity = 0.95), and
      from the Adult ADHD Self-Report Scale (ASRS) 46% (sensitivity = 0.61, specificity
      = 0.86). CONCLUSION: The prevalence of ADHD in adults seeking treatment for
      cannabis use disorders is estimated to be between 34% and 46%. The WURS paired
      with the CAARS provides excellent sensitivity and specificity for the diagnosis
      of ADHD in this population.

PMID- 27033881
TI  - The Norwegian Translation of the Adult Attention-Deficit/Hyperactivity Disorder
      Quality of Life Scale: Validation and Assessment of QoL in 313 Adults With ADHD.
AB  - OBJECTIVE: The aim of the study was to validate the Norwegian version of the
      Adult Attention-Deficit/Hyperactivity Disorder Quality of Life (AAQoL) scale and
      to explore Quality of Life (QoL) and functional outcomes in adults with ADHD.
      METHOD: A total of 313 adults with ADHD participated in the study. Data were
      collected from medical records and self-report questionnaires. Confirmatory
      factor analysis was performed to assess the model fit of the translated AAQoL.
      Chi-square statistics andttests were used to investigate sample characteristics.
      RESULTS: The analyses showed acceptable model fit between data and the model. Chi
      square = 863.179 (371df, p< .0000), root mean square error of approximation
      (RMSEA) = 0.069 (90% confidence interval [CI]), comparative fit index (CFI) =
      0.873, and Tucker-Lewis index (TLI) = 0.821. Cronbach's alpha range for the
      scales was .761 to .869. The sample was characterized by poor QoL and impairment.
      CONCLUSION: The translated AAQoL is showing good initial indications of validity
      with acceptable psychometric properties in the sample. ADHD was associated with
      impairments in QoL, symptoms, and functional outcomes.

PMID- 27033883
TI  - Internal reporting system: we must look behind the curtain.

PMID- 27033882
TI  - Imaging in acute respiratory distress syndrome.
AB  - PURPOSE: Imaging has become increasingly important across medical specialties for
      diagnostic, monitoring, and investigative purposes in acute respiratory distress
      syndrome (ARDS). METHODS: This review addresses the use of imaging techniques for
      the diagnosis and management of ARDS as well as gaining knowledge about its
      pathogenesis and pathophysiology. The techniques described in this article are
      computed tomography, positron emission tomography, and two easily accessible
      imaging techniques available at the bedside-ultrasound and electrical impedance
      tomography (EIT). RESULTS: The use of computed tomography has provided new
      insights into ARDS pathophysiology, demonstrating that ARDS does not
      homogeneously affect the lung parenchyma and that lung injury severity is widely
      distributed in the ARDS population. Positron emission tomography is a functional
      imaging technique whose value resides in adding incremental insights to
      morphological imaging. It can quantify regional perfusion, ventilation, aeration,
      lung vascular permeability, edema, and inflammation. Lung ultrasound and EIT are
      radiation-free, noninvasive tools available at the bedside. Lung ultrasound can
      provide useful information on ARDS diagnosis when x-rays or CT scan are not
      available. EIT is a useful tool to monitor lung ventilation and to assess the
      regional distribution of perfusion. CONCLUSIONS: The future of imaging in
      critical care will probably develop in two main directions: easily accessible
      imaging techniques that can be used at the bedside and sophisticated imaging
      methods that will be used to aid in difficult diagnostic cases or to advance our
      understanding of the pathogenesis and pathophysiology of an array of critical
      illnesses.

PMID- 27033884
TI  - Daily sedation interruption in children warrants further study.

PMID- 27033885
TI  - Effects of chest physiotherapy by expiratory flow increase on secretion removal
      and lung mechanics in ventilated patients: a randomized crossover study.

PMID- 27033886
TI  - Role of aspirin in patients with septic shock: a complex and intriguing
      relationship.

PMID- 27033887
TI  - Striving for an effective but parsimonious use of sedation in pediatric intensive
      care.

PMID- 27033888
TI  - Alternatives to antibiotics.

PMID- 27033889
TI  - Erratum to: Authors' response: Origin of the 24-h rest arm.

PMID- 27033890
TI  - Understanding variability of end-of-life care in the ICU for the elderly.

PMID- 27033891
TI  - Ultrasonographic diagnosis of tracheal compression.

PMID- 27033892
TI  - Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.
AB  - Our goal is to develop minimally invasive biomarkers for predicting radiation
      induced lung injury before symptoms develop. Currently, there are no biomarkers
      that can predict radiation pneumonitis. Radiation damage to the whole lung is a
      serious risk in nuclear accidents or in radiologic terrorism. Our previous
      studies have shown that a single dose of 15 Gy of x-rays to the thorax causes
      severe pneumonitis in rats by 6-8 wk. We have also developed a mitigator for
      radiation pneumonitis and fibrosis that can be started as late as 5 wk after
      radiation. METHODS: We used 2 functional SPECT probes in vivo in irradiated rat
      lungs. Regional pulmonary perfusion was measured by injection of (99m)Tc
      macroaggregated albumin. Perfused volume was determined by comparing the volume
      of distribution of (99m)Tc-macroaggregated albumin to the anatomic lung volume
      obtained by small-animal CT. A second probe, (99m)Tc-labeled Duramycin, which
      binds to apoptotic cells, was used to measure pulmonary cell death in the same
      rat model. RESULTS: The perfused volume of lung was decreased by about 25% at 1,
      2, and 3 wk after receipt of 15 Gy, and (99m)Tc-Duramycin uptake was more than
      doubled at 2 and 3 wk. There was no change in body weight, breathing rate, or
      lung histology between irradiated and nonirradiated rats at these times.
      Pulmonary vascular resistance and vascular permeability measured in isolated
      perfused lungs ex vivo increased at 2 wk after 15 Gy of irradiation. CONCLUSION:
      Our results suggest that SPECT biomarkers have the potential to predict radiation
      injury to the lungs before substantial functional or histologic damage is
      observed. Early prediction of radiation pneumonitis in time to initiate
      mitigation will benefit those exposed to radiation in the context of therapy,
      accidents, or terrorism.

PMID- 27033893
TI  - Serial 18F-FET PET Imaging of Primarily 18F-FET-Negative Glioma: Does It Make
      Sense?
AB  - PET with O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) has gained increasing
      importance for glioma management. With regard to the occurrence of (18)F-FET
      negative glioma, we investigated the value of (18)F-FET PET monitoring of
      primarily (18)F-FET-negative gliomas concerning the detection of progression and
      malignant transformation. METHODS: We included 31 patients (26 World Health
      Organization [WHO] grade II, 5 WHO grade III) with primarily (18)F-FET-negative
      glioma and available (18)F-FET PET follow-up. (18)F-FET PET analysis comprised
      maximal tumor-to-background ratio (TBRmax) and dynamic analysis of tumoral (18)F
      FET uptake over time (increasing vs. decreasing) including minimal time to peak
      (TTPmin). PET findings were correlated with MRI and clinical findings of
      progression as well as histology of recurrent tumors. RESULTS: Twenty-three of 31
      patients experienced tumor progression (median progression-free survival, 41.7
      mo). Fourteen of 23 patients showed tumoral (18)F-FET uptake concurrent to and 4
      of 23 before MRI-derived or clinical signs of tumor progression; 2 of 23 patients
      presented signs of progression in MRI when no concomitant (18)F-FET PET was
      available, but subsequent follow-up PET was positive. In 3 of 23 patients, no
      (18)F-FET uptake was detected at tumor progression. Overall, 20 of 31 primarily
      (18)F-FET-negative glioma turned (18)F-FET-positive during the follow-up. At
      first occurrence of tumoral (18)F-FET uptake, TBRmax was significantly higher in
      patients with malignant transformation (11/20) than in those without malignant
      progression (3.2 +/- 0.9 vs. 1.9 +/- 0.5; P = 0.001), resulting in a high
      detection rate for malignant transformation (for TBRmax > 2.46: sensitivity, 82%;
      specificity, 89%; negative predictive value, 80%; positive predictive value, 90%;
      and accuracy, 85%). Although static evaluation was superior to dynamic analysis
      for the detection of malignant transformation (for TTPmin <= 17.5 min:
      sensitivity, 73%; specificity, 67%; negative predictive value, 67%; positive
      predictive value, 73%; and accuracy, 70%), short TTPmin was associated with an
      early malignant transformation in the further disease course. Overall, 18 of 31
      patients experienced malignant transformation; of these, 16 of 17 (94%) evaluable
      patients showed (18)F-FET uptake at the time of malignant transformation.
      CONCLUSION: (18)F-FET PET monitoring with static and dynamic evaluation is useful
      even in primarily (18)F-FET-negative glioma, providing a high detection rate of
      both tumor progression and malignant transformation, partly before further signs
      of progression in MRI. Hence, (18)F-FET uptake indicating malignant
      transformation might influence the patient management.

PMID- 27033894
TI  - Standardization of Administered Activities in Pediatric Nuclear Medicine: A
      Report of the First Nuclear Medicine Global Initiative Project, Part 2-Current
      Standards and the Path Toward Global Standardization.
AB  - The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of
      13 international organizations with direct involvement in nuclear medicine. The
      underlying objectives of the NMGI are to promote human health by advancing the
      field of nuclear medicine and molecular imaging, encourage global collaboration
      in education, and harmonize procedure guidelines and other policies that
      ultimately lead to improvements in quality and safety in the field throughout the
      world. For its first project, the NMGI decided to consider the issues involved in
      the standardization of administered activities in pediatric nuclear medicine. It
      was decided to divide the final report of this project into 2 parts. Part 1 was
      published in this journal in the spring of 2015. This article presents part 2 of
      the final report. It discusses current standards for administered activities in
      children and adolescents that have been developed by various professional
      organizations. It also presents an evaluation of the current practice of
      pediatric nuclear medicine specifically with regard to administered activities as
      determined by an international survey of 313 nuclear medicine clinics and centers
      from 29 countries. Lastly, it provides recommendations for a path toward global
      standardization of the administration of radiopharmaceuticals in children. 

PMID- 27033895
TI  - A New Theranostic Paradigm for Advanced Thyroid Cancer.

PMID- 27033896
TI  - The Prognostic Impact of Early Change in 18F-FDG PET SUV After Neoadjuvant
      Chemotherapy in Patients with Locally Advanced Breast Cancer.
AB  - SUV, which is an indicator of the degree of glucose uptake in (18)F-FDG PET, can
      be applied as a prognostic factor in various malignant tumors. We investigated
      the prognostic impact of early changes in (18)F-FDG PET uptake in patients with
      locally advanced breast cancer who received neoadjuvant chemotherapy. METHODS: We
      retrospectively identified 87 patients who were treated with neoadjuvant
      chemotherapy followed by surgery for locally advanced breast cancer. All patients
      underwent (18)F-FDG PET at baseline and after 3 cycles of neoadjuvant
      chemotherapy, and the SUVmax of the primary tumor was assessed in each scan.
      Pathologic slides were retrospectively reviewed, and the residual cancer burden
      (RCB) index was calculated to estimate pathologic response. RCB-0 indicates no
      residual disease; patients with residual disease were categorized as RCB-1
      (minimal residual disease), RCB-2 (moderate residual disease), or RCB-3
      (extensive residual disease). RESULTS: There was a negative correlation between
      reduction in SUVmax and RCB index (r = -0.408; P < 0.001). On multivariate
      analysis, DeltaSUVmax was a significant independent prognostic factor for
      recurrence-free and overall survival, and the respective adjusted hazard ratios
      were 0.97 (95% confidence interval, 0.95-0.99; P = 0.001) and 0.97 (95%
      confidence interval, 0.95-0.99; P = 0.015). When patients were categorized into
      groups according to pathologic response (RCB index <= 1 vs. >= 2) and metabolic
      response (DeltaSUVmax <= 66.4% vs. > 66.4%), metabolic responders had
      significantly better recurrence-free and overall survival than metabolic
      nonresponders among poor-pathologic-response patients. In contrast, among
      metabolic responders, there was no survival difference according to pathologic
      response. CONCLUSION: The early change in (18)F-FDG PET SUVmax after third-cycle
      neoadjuvant chemotherapy is an independent and good prognostic marker beyond
      pathologic response in patients with locally advanced breast cancer. We suggest
      that in these patients, the use of DeltaSUVmax should be considered not only for
      the assessment of tumor response but for the prediction of posttreatment outcome.

PMID- 27033897
TI  - 68Ga-DOTATOC PET/CT in Patients with Iodine- and 18F-FDG-Negative Differentiated
      Thyroid Carcinoma and Elevated Serum Thyroglobulin.
AB  - : This study evaluated the impact of 68Ga-DOTATOC PET/CT in detecting recurrence
      or metastases in differentiated thyroid carcinoma (DTC) patients with elevated
      serum thyroglobulin and both negative radioiodine imaging and negative 18F-FDG
      PET/CT. METHODS: 68Ga-DOTATOC PET/CT (CT without contrast, low-dose) was
      performed on average 6 wk after negative 18F-FDG PET/CT (CT contrast-enhanced,
      full-dose) in 15 consecutive radioiodine-negative DTC patients with elevated and
      rising thyroglobulin. Visual assessment of 68Ga-DOTATOC PET/CT images used a 4
      point scale for classification of lesions (0, no pathologic findings; 1, benign;
      2, equivocal; 3, malignant). PET findings were correlated with the histologic
      subtype of tumor, levels of serum thyroglobulin, and morphologic findings on full
      dose CT and neck ultrasound. Histology or clinical and imaging follow-up served
      as a reference standard. Analysis was performed on a patient and lesion basis.
      RESULTS: 68Ga-DOTATOC PET/CT was true-positive in 5 patients (10 tumor lesions)
      and was false-positive in 1 patient. The rate of positive 68Ga-DOTATOC PET/CT was
      significantly higher in poorly differentiated/oxyphilic carcinomas (4/4 patients)
      than in papillary (1/5) or follicular (0/6) tumors. Thyroglobulin levels tended
      to be higher in patients with tumor localization on 68Ga-DOTATOC PET/CT, but
      differences were not significant. In 2 of 5 patients with true-positive findings
      on 68Ga-DOTATOC PET/CT, CT alone but not ultrasound identified 2 of 10 tumor
      lesions, but in both patients 68Ga-DOTATOC-PET/CT revealed further tumor lesions
      not detected on CT alone. CONCLUSION: 68Ga-DOTATOC PET/CT should be considered in
      the case of negative 18F-FDG PET/CT in radioiodine-negative DTC patients with
      elevated and rising thyroglobulin. Imaging with 68Ga-DOTATOC appears promising
      especially in poorly differentiated and oxyphilic subtypes of DTC.

PMID- 27033898
TI  - Identification and functional analysis of porcine basic helix-loop-helix
      transcriptional factor 3 (TCF3) and its alternative splicing isoforms.
AB  - The transcription factor 3 (TCF3) is a basic helix-loop-helix transcription
      factor and is essential for lymphocyte development and epithelial-mesenchymal
      transition. The splicing isoform, genomic organization and physiological roles of
      TCF3 have not been elucidated well in pig. Based on RNA-seq database, four
      alternative splicing isoforms were identified. Splicing isoforms TCF3(E12),
      TCF3(E47), and TCF3A expressed globally in porcine tissues, but TCF3B mainly
      expressed in spleen and endoderm derived tissues, such as pancreas and lung. The
      functional analysis showed that TCF3(E12), TCF3(E47), and TCF3B were translocated
      exclusively into nuclei, yet TCF3A was distributed in cytoplasm. The
      investigation of clinical specimens showed that TCF3 expression was significantly
      reduced in spleen tissues that were infected by classical swine fever virus
      (CSFV). This study is for the first time to report two novel splicing isoforms
      TCF3A and TCF3B, which may play an important role in lymphocyte maturation and
      have the correlation with CSFV evasion. 

PMID- 27033899
TI  - Effect of alpha-Amylase, Papain, and Spermfluid treatments on viscosity and semen
      parameters of dromedary camel ejaculates.
AB  - Ejaculates from five clinically healthy dromedary camels (Camelus dromedarius)
      were used to evaluate the effects of different enzymatic treatments (Amylase,
      Papain, Spermfluid) on liquefaction and seminal parameters. After collection,
      ejaculates were divided into 5 aliquots: (1) kept undiluted (control); or diluted
      1:1 with: (2) Tris-Citrate-Fructose (TCF), (3) TCF containing Amylase, (4) TCF
      containing Papain or (5) Spermfluid containing Bromelain. At 120 min after
      dilution, each aliquot was evaluated, at 20-min intervals, for viscosity,
      motility, viability and agglutination. Only the aliquots diluted with TCF
      containing Papain underwent complete liquefaction. Sperm motility decreased
      significantly during the observation times, except for the samples diluted with
      Spermfluid (P=0.005). Diluted samples showed different levels of agglutination,
      with the lowest being observed in the control and the highest in the Papain
      treated samples. The viscosity of dromedary camel ejaculates could be effectively
      reduced by using the proteolytic enzyme Papain.

PMID- 27033900
TI  - Serum starvation and thymidine double blocking achieved efficient cell cycle
      synchronization and altered the expression of p27, p53, bcl-2 in canine breast
      cancer cells.
AB  - Cell synchronization is an approach to obtain cell populations of the same stage,
      which is a prerequisite to studying the regulation of cell cycle progression in
      vivo. Serum starvation and thymidine double blocking (TdR) are two important
      practices in studying cell cycle synchronization. However, their effects on
      canine cancer cells as well as the regulatory mechanisms by these two methods are
      poorly understood. In this study, we determined the optimum conditions of serum
      starvation and TdR and their effects on cell cycle synchronization. We further
      explored the involvement of PI3K/Akt signaling pathway in the cell cycle
      synchronization by investigating the expression of three key genes (p27, p53 and
      bcl-2). Serum starvation resulted in a reversible cell cycle arrest and
      synchronously progress through G0/G1. The highest percentage of CHMm cells
      (87.47%) in G0/G1 stage was obtained after 42 h incubation with 0.5% fetal bovine
      serum (FBS). TdR double blocking could arrest 98.9% of CHMm cells in G1/S phase
      (0 h of release), and could arrest 93.74% of CHMm cells in S phase after 4h of
      release. We also found that the p27, p53, bcl-2 genes were most highly expressed
      in G0/G1 phase. Our current work revealed that serum starvation and TdR methods
      could achieve sufficient synchronization of CHMm cells. Moreover, the expression
      of p27, p53 and bcl-2 genes was related to cyclical movements and apoptosis. Our
      results will provide a new insight into cell cycle regulation and reprogramming
      of canine cancer cells induced by serum starvation and TdR blocking.

PMID- 27033901
TI  - Experimental infection of IS/885/00-like infectious bronchitis virus in specific
      pathogen free and commercial broiler chicks.
AB  - Pathogenesis of an IS/885/00-like (IS/885) strain of variant infectious
      bronchitis virus (IBV) was examined in one day old specific pathogen free (SPF)
      and commercial broiler chicks. Chicks were humanely euthanized at 3, 6, 9, 12,
      15, 21 and 28 days post infection (dpi) for necropsy examination, and tissues
      were collected for histopathology and virus detection by reverse transcription
      polymerase chain reaction (RT-PCR). Respiratory clinical signs and gross lesions
      consisting of tracheal caseous exudate and plugs, and swollen kidneys (with or
      without) urate deposits were observed in SPF and broiler chicks. The onset of
      disease developed more slowly and were of lesser severity in broiler compared to
      SPF chicks, reflecting the inhibitory effects of the IBV maternal-antibodies in
      the broiler chicks or genetic/strain susceptibility, or both. Head swelling was
      observed in one infected broiler chick at 15 dpi and the virus was recovered by
      RT-PCR and isolation. In the IS/885-infected SPF chicks, cystic oviducts were
      found in two female chicks. IS/885 was isolated from the cystic fluid. Using
      ELISA, low to moderate levels of the antibodies to IBV was detected in the SPF
      compared to broiler infected chicks.

PMID- 27033902
TI  - Genome sequencing of a virulent avian Pasteurella multocida strain GX-Pm reveals
      the candidate genes involved in the pathogenesis.
AB  - Pasteurella multocida (P. multocida) was first shown to be the causative agent of
      fowl cholera by Louis Pasteur in 1881. First genomic study was performed on an
      avirulent avian strain Pm70, and until 2013, two genomes of virulent avian
      strains X73 and P1059 were sequenced. Comparative genome study supplied important
      information for further study on the pathogenesis of fowl cholera. In the
      previous study, a capsular serotype A strain GX-Pm was isolated from the liver of
      a chicken, which died during an outbreak of fowl cholera in 2011. The strain
      showed multiple drug resistance and was highly virulent to chickens. Therefore,
      the present study performed the genome sequencing and a comparative genomic
      analysis to reveal the candidate genes involved in virulence of P. multocida.
      Sequenced draft genome sequence of GX-Pm was 2,292,886 bp, contained 2941 protein
      coding genes, 5 genomic islands, 4 IS elements and 2 prophage regions.
      Notability, all the predicted drug-resistance genes were included in predicted
      genomic islands. A comparative genome study on virulent avian strains P1059, X73
      and GX-Pm with the avirulent avian strain Pm 70 indicated that 475 unique genes
      were only identified in either of virulent strains but absent in the avirulent
      strain. Among these genes, 20 genes were contained within genomes of all three
      virulent strains, including a few of putative virulence genes. Further
      characterization of the pathogenic functions of these genes would benefit the
      understanding of pathogenesis of fowl cholera.

PMID- 27033903
TI  - African swine fever virus introduction into the EU in 2014: Experience of Latvia.
AB  - African swine fever (ASF) virus was introduced in Latvia in June 2014. Thirty-two
      outbreaks in domestic pigs and 217 cases in wild boar were notified in 2014.
      Twenty-eight outbreaks (87.5%) were primary outbreaks. The contagiosity within
      pig herds was low. Failure to use simple biosecurity measures to reduce the
      chance of virus introduction, for example by inadvertent feeding of locally
      produced virus contaminated fodder were the main causes for the outbreaks in
      backyard holdings. The infection in wild boar survived locally in two different
      areas with a low prevalence and a slow spread. The persistence of the infection
      in wild boar within an area was most probably linked to wild boar scavenging the
      carcasses of infected wild boar. 

PMID- 27033904
TI  - The influence of prostaglandin E2 on the production of IFN-gamma by bovine
      CD4(+), CD8(+) and WC1(+) T cells.
AB  - The aim of these studies was to assess the influence of prostaglandin E2 (PGE2)
      on the production of interferon-gamma (IFN-gamma) by bovine CD4(+), CD8(+), and
      WC1(+) T cells and furthermore, should this effect exist, to identify the E
      prostanoid (EP) receptor subtype(s) responsible for this influence. We here
      report that exposure of bovine peripheral blood mononuclear cells (PBMCs) to PGE2
      significantly and dose-dependently decreased the percentage of IFN-gamma
      producing CD4(+) and CD8(+) T cells. It was also shown that PGE2 reduced IFN
      gamma production by WC1(+) T cells, but this effect was not dose dependent. The
      impairment of IFN-gamma production should be recognized as an anti-inflammatory
      and immunosuppressive action, thus the obtained results confirm the paradoxical
      status of PGE2 as a proinflammatory factor with immunosuppressive activity. The
      blockade of EP1, EP2, EP3, and EP4 receptors did not prevent PGE2-induced
      reduction of IFN-gamma production by CD4(+) and CD8(+) T cells, indicating that
      this effect of PGE2 is not mediated through EP receptors. On the contrary, the
      blockade of either EP2 or EP4 receptors, but not EP1 or EP3 receptors, prevented
      the PGE2-induced reduction of percentage of IFN-gamma-producing WC1(+) T cells.
      These findings indicate that the ability of PGE2 to impair IFN-gamma production
      by WC1(+) T cells is mediated via EP2 and EP4 receptors. These results suggest
      the possibility of pharmacological manipulation of IFN-gamma production by WC1(+)
      T cells via selective antagonists and agonists of EP2 and EP4 receptors. 

PMID- 27033905
TI  - Comparison of the isoflurane concentration of using dexketoprofen or methadone at
      premedication during orthopedic surgery in dogs.
AB  - Thirty-two dogs were used in this prospective, randomized, clinical and double
      blinded study. Dexmedetomidine was administered at 1 MUg/kg IV, and randomly each
      dog received dexketoprofen 1 mg/kg IV (group DK) or methadone 0.2 mg/kg IV (group
      M). Dogs were induced with propofol and maintained with isoflurane in 100%
      oxygen. During surgery, the isoflurane concentration was changed depending on
      clinical signs of depth of anesthesia. Fentanyl and propofol could be used as
      required. Qualities of sedation and recovery were evaluated. A generalized linear
      mixed model or Mann-Whiney U test was used, and P<0.05 was considered
      statistically significant. No significant differences were observed between
      groups in the qualities of sedation and recovery, isoflurane concentration and in
      the total amount of fentanyl and propofol used intraoperatively. This study shows
      that the administration of dexketoprofen at 1 mg/kg IV at premedication required
      a similar isoflurane concentration to maintain anesthesia as methadone at 0.2
      mg/kg IV during orthopedic surgery in dogs. Further analgesia is recommended
      intraoperatively, because of the need of fentanyl and propofol in same animals in
      both groups.

PMID- 27033906
TI  - Fecal dysbiosis in miniature dachshunds with inflammatory colorectal polyps.
AB  - Chronic gastrointestinal disease is associated with the alteration of
      gastrointestinal microbiota. Inflammatory colorectal polyps (ICRPs) are commonly
      observed in miniature dachshunds (MDs) in Japan and are characterized by multiple
      polyps that are restricted in the colorectal mucosa with severe neutrophil
      infiltration. This study was aimed to compare the fecal microbiota of ICRP
      affected MDs with that of healthy MDs. High-throughput sequencing of amplicons
      derived from the V3-V4 region of the 16S rRNA gene was applied using the Illumina
      MiSeq system. Principal coordinates analysis revealed that fecal microbiota of
      ICRP-affected MDs was significantly altered compared with that of healthy MDs.
      Proportions of Fusobacteriaceae, Helicobacteraceae, Porphyromonadaceae, and
      Turicibacteraceae were significantly more abundant in ICRP-affected MDs, while
      those of Lachnospiraceae were significantly less abundant in ICRP-affected MDs
      compared with healthy MDs. These results suggest that the dysbiosis is associated
      with ICRPs and is a potential therapeutic target, though further investigations
      are needed. 

PMID- 27033907
TI  - Ligation of porcine Fc gamma receptor III inhibits levels of antiviral cytokine
      in response to PRRSV infection in vitro.
AB  - PRRSV infection ADE facilitates the attachment and internalization of the virus
      onto macrophages through Fc receptor-mediated endocytosis. FcgammaR III is the
      activating receptor with a tyrosine-based activating motif (ITAM) in its
      cytoplasmic tail, where up-regulates phagocytosis. However, porcine FcgammaR
      III's role in the antiviral immune response to PRRSV infection has not been
      studied. In this study, our results indicated that selective activation of
      porcine FcgammaR III in PAM cells down-regulated significantly mRNA levels of IFN
      alpha and TNF-alpha post-pretreatment, and up-regulated significantly mRNA level
      of IL-10 post-pretreatment, suggesting that porcine FcgammaR III signal can
      inhibit the transcriptional levels of innate antiviral cytokine in host cells.
      Simultaneously, PRRSV infection assay mediated by FcgammaR III indicated that
      selective activation of porcine FcgammaR III in PAM cells inhibited significantly
      mRNA levels of IFN-alpha and TNF-alpha, and enhanced significantly mRNA level of
      IL-10, and increased significantly viral mRNA levels, in response to PRRSV
      infection, suggesting that FcgammaR III ligation can inhibit the antiviral immune
      response to PRRSV infection. These results elucidated that the one mechanism of
      PRRSV-ADE regulated via porcine FcgammaRIII may be by decreasing antiviral
      cytokine levels, facilitating viral replication. 

PMID- 27033908
TI  - Distribution of bovine alpha-herpesviruses and expression of toll-like receptors
      in the respiratory system of experimentally infected calves.
AB  - This study provides an initial analysis of the toll-like receptors (TLRs) that
      might be implicated in alpha-herpesvirus infection of the bovine respiratory
      system. A significant variation in the expression of TLR3 and TLRs 7-9 during
      bovine herpesvirus type 1 (BoHV-1) and 5 (BoHV-5) acute infections and
      particularly an up-regulation during viral reactivation in respiratory tissues
      has been demonstrated. Furthermore, viral distribution in the respiratory tract
      of BoHV-1- and BoHV-5-infected calves at different stages of the infectious cycle
      was analysed. The wide distribution of BoHV DNA in the respiratory tract during
      acute infection was restricted during latent infection and the subsequent
      reactivation of BoHV-1 and BoHV-5. Overall, the findings presented here
      contribute to the knowledge on the replication and dissemination of bovine alpha
      herpesviruses. Furthermore, some of the immune factors triggered in the host that
      determine the different outcomes of infection by two closely related pathogens of
      cattle have been elucidated. 

PMID- 27033909
TI  - The effects of Mycoplasma hyopneumoniae on porcine circovirus type 2 replication
      in vitro PK-15 cells.
AB  - Porcine circovirus type 2 (PCV2) is the causative agent of postweaning
      multisystemic wasting syndrome (PMWS). Mycoplasma hyopneumoniae (Mhp) is a very
      well-known co-factor that potentially enhances PCV2 replication and thus the
      development of PMWS. However, co-infection with Mhp and PCV2 in vivo under
      different conditions can produce divergent clinical signs and lesions. In this
      study, PCV2 replication could be enhanced by subsequent co-inoculation with Mhp
      (PCV2+Mhp) in a time and dose dependent method, but not by prior (Mhp+PCV2) or
      simultaneous (Mhp/PCV2) co-inoculation. Furthermore, different magnitudes of PCV2
      infected cells, varying from 150% +/- 14% to 351% +/- 28%, were detected when co
      infected with different Mhp strains. The relative percentage of PCV2-infected
      cells greatly decreased from 351% +/- 28 to 141% +/- 18 when the Mhp strain was
      treated with UV light for 12 h. These results offer the evidences to better
      understand the complex clinical syndromes in Mhp/PCV2 co-infection cases, and the
      occurrence of PMWS.

PMID- 27033910
TI  - Isolation and characterization of bacteria with antibacterial properties from
      Nile tilapia (Oreochromis niloticus).
AB  - One hundred and twenty bacterial isolates were obtained from the intestinal mucus
      of Nile tilapia (Oreochromis niloticus) and screened for antagonistic activity
      and adherence abilities. Based on in vitro antagonism against two pathogens
      (Streptococcus iniae and Edwardsiella piscicida), five isolates were selected and
      identified by 16S rRNA gene sequence analysis. All antagonistic isolates were
      affiliated to the genus Bacillus, which showed inhibitory activity against S.
      iniae. Only the isolate B191 (closely related to Bacillus mojavensis) inhibited
      the growth of both pathogens. Moreover, isolate B191 adhered significantly better
      to fish intestinal mucus than other antagonistic isolates. According to our
      results, these bacterial isolates, particularly isolate B191, should be further
      studied to explore their probiotic effects under in vivo conditions. 

PMID- 27033911
TI  - The effects of melamine on humoral immunity with or without cyanuric acid in
      mice.
AB  - Melamine is an industrial chemical with high nitrogen content. When added to the
      pet food and milk it can falsely elevate the apparent protein concentration
      readings. Cyanuric acid related structurally to melamine has a strong mutual
      affinity with melamine. The combined ingestion of melamine and cyanuric acid was
      considered to be responsible for the crystalluria, kidney stones and subsequent
      renal failure in animals. In our previous investigation, we demonstrated that
      melamine alone or its combination with cyanuric acid appears to be toxic to the
      immune system in mice. The objective of this study was to investigate the
      potential effects of melamine on humoral immunity with or without cyanuric acid
      in mice. In comparison to control group, a significantly lower content of plasma
      cells expressing CD138 were observed in mixture groups of melamine and cyanuric
      acid with both middle and high doses. The co-administration of melamine and
      cyanuric acid resulted in a significant decreasing in blimp-1 protein expression
      and the contents of sIgA, C3, IL-21 and IL-4 compared with the control group.
      Moreover, our data clearly showed that melamine-related toxicity suppressed the
      production of IL-6 and IL-10 in a dose-dependent manner. Also, the animals from
      mixture of melamine and cyanuric acid with high dose group exhibited a
      significantly lower expression of gata-3 protein, The results from the present
      study suggested that the exposure to melamine alone or combination with cyanuric
      acid had certain humoral immunotoxicity in mice, especially when ingested in high
      dosage. 

PMID- 27033912
TI  - Subtilase cytotoxin-encoding subAB2 variants in verotoxin-producing Escherichia
      coli strains isolated from goats and sheep.
AB  - Subtilase cytotoxin (SubAB) is a cytotoxin which might contribute to the
      virulence of verotoxin-producing Escherichia coli (VTEC) strains in humans. Three
      variants of SubAB encoding genes have been described (subAB1, subAB2-1, and
      subAB2-2) and it has been suggested that the strains positive for two variants of
      subAB may be more pathogenic for humans. In this study, 188 subAB2-positive VTEC
      strains isolated from goats and sheep were investigated for the presence of the
      subAB2-1 and subAB2-2 variants by PCR. Eighty-one of the 132 (61.4%) caprine
      strains and 36 of the 56 (64.3%) ovine strains possessed the subAB2-1 variant and
      all ovine and caprine strains, except one, were positive for the subAB2-2
      variant. The results of this study show for first time that the subAB2-1 and
      subAB2-2 variants are found in caprine subAB2-positive VTEC strains and confirm
      that both subAB2 variants are detected in ovine subAB2-positive VTEC strains.
      Since no significant difference in the presence of both subAB2 variants was found
      among strains belonging to serotypes associated with severe illness in humans and
      strains not belonging to these serotypes, the occurrence of two subAB2 variants
      seems not to be associated with a higher risk of severe disease in humans. 

PMID- 27033913
TI  - The effects of ryanodine receptor (RYR1) mutation on natural killer cell
      cytotoxicity, plasma cytokines and stress hormones during acute intermittent
      exercise in pigs.
AB  - Stress susceptibility has been mapped to a single recessive gene, the ryanodine
      receptor 1 (RYR1) gene or halothane (Hal) gene. Homozygous (Hal(nn)), mutated
      pigs are sensitive to halothane and susceptible to Porcine Stress Syndrome (PSS).
      Previous studies have shown that stress-susceptible RYR1 gene mutated homozygotes
      in response to restraint stress showed an increase in natural killer cell
      cytotoxicity (NKCC) accompanied by more pronounced stress-related hormone and
      anti-inflammatory cytokine changes. In order to determine the relationship of a
      RYR1 gene mutation with NKCC, plasma cytokines and stress-related hormones
      following a different stress model - exercise - 36 male pigs (representing
      different genotypes according to RYR1 gene mutation: NN, homozygous dominant; Nn,
      heterozygous; nn, homozygous recessive) were submitted to an intermittent
      treadmill walking. During the entire experiment the greatest level of NKCC and
      the greatest concentrations of interleukin (IL-) 6, IL-10, IL-12, interferon (IFN
      )gamma and tumor necrosis factor-alpha and stress-related hormones (adrenaline,
      prolactin, beta-endorphin) were observed in nn pigs, and the greatest
      concentration of IL-1 and growth hormone in NN pigs. Immunostimulatory effects of
      intermittent exercise on NKCC in nn pigs were concomitant with increases in IL-2,
      IL-12 and IFN-gamma, the potent NKCC activators. Our findings suggest that stress
      susceptible pigs RYR1 gene mutated pigs develop a greater level of NKCC and
      cytokine production in response to exercise stress. These results suggest that
      the heterogeneity of immunological and neuroendocrine response to exercise stress
      in pigs could be influenced by RYR1 gene mutation. 

PMID- 27033914
TI  - Inter- and intraobserver variability of (semi-)quantitative parameters commonly
      used in feline thyroid scintigraphy.
AB  - The aim of this study was to assess inter- and intraobserver variability of
      commonly used semi-quantitative and quantitative parameters in feline thyroid
      scintigraphy: thyroid to salivary gland ratio (T/S), thyroid to background ratio
      (T/B) and the percentage technetium pertechnetate uptake for the thyroid glands
      (%TcUT). These parameters are being used to diagnose thyroid disease and to
      assess its severity, but may be influenced by operator related factors when
      processing the images. Additionally, inter- and intraobserver variability of the
      percentage technetium pertechnetate uptake for the salivary glands was determined
      (%TcUSG). The study included technetium pertechnetate scans of 100 hyperthyroid
      cats. Variability within and between three observers was determined using a
      random effects model and variance components were estimated by the restricted
      maximum likelihood procedure. The %TcU for the thyroid and salivary glands, as
      well as the T/S ratio, showed little to no difference in inter- and intraobserver
      variability, whereas this was clearly present for the T/B ratio. Overall, the T/S
      ratio and %TcUSG showed a good repeatability and reproducibility with low inter-
      and intraobserver variabilities. Inter- and intraobserver variability was higher
      for the %TcUT, however variations were still considered to be acceptable. On the
      contrary, inter- and intraobserver variability was clearly larger for the T/B
      ratio. These findings suggest the preferential use of the T/S ratio or %TcU,
      especially in facilities with a less experienced staff. 

PMID- 27033915
TI  - M1 and M2 macrophage recruitment during tendon regeneration induced by amniotic
      epithelial cell allotransplantation in ovine.
AB  - Recently, we have demonstrated that ovine amniotic epithelial cells (oAECs)
      allotransplanted into experimentally induced tendon lesions are able to stimulate
      tissue regeneration also by reducing leukocyte infiltration. Amongst leukocytes,
      macrophages (Mphi) M1 and M2 phenotype cells are known to mediate inflammatory
      and repairing processes, respectively. In this research it was investigated if,
      during tendon regeneration induced by AECs allotransplantation, M1Mphi and M2Mphi
      phenotype cells are recruited and differently distributed within the lesion site.
      Ovine AECs treated and untreated (Ctr) tendons were explanted at 7, 14, and 28
      days and tissue microarchitecture was analyzed together with the distribution and
      quantification of leukocytes (CD45 positive), Mphi (CD68 pan positive), and
      M1Mphi (CD86, and IL12b) and M2Mphi (CD206, YM1 and IL10) phenotype related
      markers. In oAEC transplanted tendons CD45 and CD68 positive cells were always
      reduced in the lesion site. At day 14, oAEC treated tendons began to recover
      their microarchitecture, contextually a reduction of M1Mphi markers, mainly
      distributed close to oAECs, and an increase of M2Mphi markers was evidenced.
      CD206 positive cells were distributed near the regenerating areas. At day 28
      oAECs treated tendons acquired a healthy-like structure with a reduction of
      M2Mphi. Differently, Ctr tendons maintained a disorganized morphology throughout
      the experimental time and constantly showed high values of M1Mphi markers. These
      findings indicate that M2Mphi recruitment could be correlated to tendon
      regeneration induced by oAECs allotransplantation. Moreover, these results
      demonstrate oAECs immunomodulatory role also in vivo and support novel insights
      into their allogeneic use underlying the resolution of tendon fibrosis.

PMID- 27033916
TI  - Assessment of right ventricular function by feature-tracking echocardiography in
      conscious healthy dogs.
AB  - Advanced two-dimensional echocardiographic techniques allow strain (S) analysis
      of regional function and thus can provide information on regional myocardial
      deformation. Feature-tracking echocardiography (FTE) is based on a mono
      dimensional technology and may offer more detailed information about septal
      deformation because it can analyse the activity of left- and right-sided septal
      fibres separately. The present study aimed to quantify global and regional (free
      wall and septal) right ventricular (RV) longitudinal S and strain rate (SR). We
      also investigated the relationships of S and SR with age, sex, weight, breed
      (sighthound breed vs other breeds), and heart rate. Cine loops were acquired from
      the left apical four-chamber view, optimized for the RV, in 60 dogs. The within
      day and between-day intra-observer coefficient of variation for global RV S and
      SR in normal dogs using FTE was acceptable (<8.5%). Global longitudinal S (GLS)
      and SR showed a significant correlation with breed. GLS showed a significant weak
      positive correlation with weight. Global longitudinal SR showed a significant
      moderate negative correlation with heart rate. No correlation was found between
      GLS/SR and age. There was no significant difference between male and female dogs.
      This study shows, for the first time, that a novel FTE algorithm represents a
      promising and feasible non-invasive technique to assess RV myocardial function
      (free wall and septal deformation) in dogs. Based on our results, sighthound
      breeds appear to need specific reference values. 

PMID- 27033917
TI  - Coinfection by Ureaplasma spp., Photobacterium damselae and an Actinomyces-like
      microorganism in a bottlenose dolphin (Tursiops truncatus) with pleuropneumonia
      stranded along the Adriatic coast of Italy.
AB  - A case of pleuropneumonia is reported in an adult male bottlenose dolphin
      (Tursiops truncatus) found stranded in 2014 along the Central Adriatic coast of
      Italy. A severe pyogranulomatous pneumonia and thoracic lymphadenopathy were
      present at necropsy. Numerous Splendore-Hoeppli bodies were found microscopically
      scattered throughout the lung. Histochemical evidence of Actinomyces-like
      organisms was obtained from the pulmonary parenchyma, with a strain of
      Photobacterium damselae subsp. piscicida and Ureaplasma spp. being also isolated
      from the same tissue. For the latter, a genome fragment of approximately 1400 bp
      from the 16s rDNA was amplified and sequenced. BLAST analysis revealed 100%
      identity with an uncultured Ureaplasma spp. (JQ193826.1).

PMID- 27033918
TI  - Evaluation of endothelin-1 and MMPs-2, -9, -14 in cerebrospinal fluid as indirect
      indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism.
AB  - Chronic canine hypothyroidism is associated with blood-brain barrier (BBB)
      disruption. We hypothesized that this change is mediated by endothelin-1(ET-1)
      and matrix metalloproteinases (MMP) -2, -9, and -14, as evidenced by increased
      concentrations of these proteins in cerebrospinal fluid (CSF) compared to
      controls. CSF from 18 dogs, 9 controls and 9 with experimentally induced
      hypothyroidism was collected before and 6, 12, and 18 months after induction of
      hypothyroidism. Concentrations of ET-1 using an ELISA kit, and for MMP-2, -9, and
      -14 using gelatinase zymography were measured in CSF. ET-1 was undetectable in
      CSF of control and hypothyroid dogs at all time-points. Constitutively expressed
      MMP-2 was detectable in CSF samples in all dogs at all time-points. No other MMPs
      were detectable in CSF. No differences in CSF concentrations of ET-1 and MMP-2,
      9, and 14 were found between hypothyroid and euthyroid dogs. Therefore, ET-1 and
      MMP-2, 9, and 14 are unlikely to be primary mediators of BBB damage in
      chronically hypothyroid dogs.

PMID- 27033919
TI  - Effects of oral administration of caffeine on some physiological parameters and
      maternal behaviour of sows at farrowing.
AB  - Caffeine has been demonstrated to have a protective effect on neonatal viability
      of piglets. In order to assess whether caffeine, administered to parturient sows,
      also affects maternal behaviour, respiratory rate, and dopamine, nitric oxide and
      serotonin plasma levels, 20 sows, with induced parturition, received orally 27
      mg/kg of body weight of caffeine (T group; n=10) or not (NT group; n=10), on day
      113 of gestation. Treatment did not affect the farrowing length. There were less
      stillborn piglets in T group than NT group (0.67 vs 2.44; P<0.05), whereas no
      differences in dead piglets at 24h from birth was observed. Caffeine did not
      affect physiological parameters of sows, as the behaviour score of sows laying on
      belly was reduced (P<0.05). In conclusion, although the present study was carried
      out with a limited number of sows, administration of caffeine to parturient sows
      has the potential for reducing the number of stillborn.

PMID- 27033920
TI  - Evaluation of apoptosis-associated protein (Bcl-2, Bax, cleaved caspase-3 and
      p53) expression in canine mammary tumors: An immunohistochemical and prognostic
      study.
AB  - Apoptosis is an important process involved in pathogenesis and progression of
      neoplasia. However, it has been not so far extensively investigated in canine
      mammary tumors (CMTs). Therefore the aim of our study was to determine Bcl-2,
      Bax, cleaved caspase-3 (CC3) and p53 expression in CMTs and evaluate their
      correlation with host/tumor factors, and overall survival (OS). Bcl-2 expression
      was often found in benign lesions and in patients with low TNM stage. Expression
      of Bax, CC3 and p53 was observed in malignant CMTs. The expression of apoptosis
      associated proteins was not significantly associated with OS. A positive-p53
      status was significantly related with poorer tumor differentiation, higher
      mitotic index (MI), more invasive growth, necrosis, and occurred often in CMTs
      from large breed dogs. In the shorter-survival group of dogs (<=18 months), a
      positive correlation was found between CC3 and Bcl-2 expression; CC3 and MI,
      ERalpha and p53 expression, while in the longer-survival group (>18 months) CC3
      expression was negatively correlated with ERalpha, whereas p53 expression was
      positively correlated with MI. We confirmed the usefulness of such parameters as:
      tumor size, MI, type of growth, tumor metastasis and TNM stage in predicting OS
      in a univariate analysis. In multivariate analysis we identified age as an
      independent prognostic factor for OS. Expression of single apoptosis-associated
      protein should not be used as a prognostic marker. However, we showed significant
      correlation patterns of expression of proteins involved in apoptotic-signaling
      pathways in shorter- and longer survival groups. So far, there have been only a
      few similar reports published.

PMID- 27033921
TI  - Detection of plasmid mediated colistin resistance (MCR-1) in Escherichia coli and
      Salmonella enterica isolated from poultry and swine in Spain.
AB  - Recent findings suggest that use of colistin as a last resort antibiotic is
      seriously threatened by the rise of a new plasmid mediated mechanism of
      resistance (MCR-1). This work identifies, for the first time in Southern Europe,
      the gene mcr-1 in nine strains from farm animals (poultry and swine)
      corresponding to five Escherichia coli and four Salmonella enterica, among which
      three belong to serovar Typhimurium and one to Rissen. The MCR-1 was found
      encoded by a plasmid highly mobilizable by conjugation to the E. coli J53 strain.
      Two E. coli strains carried two determinants, mcr-1 plus pmrA or pmrB mutations,
      known to confer colistin resistance. 

PMID- 27033922
TI  - Risk factors for cluster seizures in canine idiopathic epilepsy.
AB  - Cluster seizures (CS), two or more seizures within a 24-hour period, are reported
      in 38-77% of dogs with idiopathic epilepsy (IE). Negative outcomes associated
      with CS include a reduced likelihood of achieving seizure freedom, decreased
      survival time and increased likelihood of euthanasia. Previous studies have found
      factors including breed, sex and neuter status are associated with CS in dogs
      with IE; however, only one UK study in a multi-breed study of CS in IE patients
      exists to the author's knowledge, and thus further data is required to confirm
      these results. Data from 384 dogs treated at a multi-breed canine specific
      epilepsy clinic were retrospectively collected from electronic patient records.
      384 dogs were included in the study, of which nearly half had a history of CS
      (49.1%). Dogs with a history of CS had a younger age at onset than those without
      (p = 0.033). In a multivariate model, three variables predicted risk of CS: a
      history of status epilepticus (p = 0.047), age at seizure onset (p = 0.066) and
      breed (German Shepherd Dog) (p < 0.001). Dogs with a history of status
      epilepticus and dogs with an older age at seizure onset were less likely to be
      affected by cluster seizures. German Shepherd Dogs (71% experiencing CS) were
      significantly more likely to suffer from CS compared to Labrador Retrievers (25%)
      (p < 0.001). There was no association between sex, neuter status, body size and
      CS. Further studies into the pathophysiology and genetics of CS are required to
      further understand this phenomenon.

PMID- 27033923
TI  - The origin of Pasteurella multocida impacts pathology and inflammation when
      assessed in a mouse model.
AB  - Host-pathogen interactions of Pasteurella multocida isolates of different origin
      were studied in a mouse model, focusing on pathology, bacterial load and
      expression of the metalloproteinase MMP9 and its inhibitor TIMP1. Intranasal
      inoculation with one of three doses (10(6), 10(4), 10(2)CFU) of an isolate from
      porcine pneumonia or fowl cholera showed marked differences between the two
      isolates. The avian isolate was highly pathogenic with severe signs of
      necrotizing pneumonia, liver necrosis and high bacterial load in lung and liver.
      Clinical signs and pathology related to the porcine isolate were dose dependent
      and consisted of exudative bronchopneumonia, abscess formation in liver and a
      lower bacterial load in lung and liver. Both isolates caused increased expression
      of MMP9 and TIMP1. In conclusion, evaluation and comparison of pathogenicity and
      host-pathogen interaction of P. multocida isolates from different hosts is
      possible in the intranasal murine model. 

PMID- 27033924
TI  - Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease
      model as a tool for vaccine testing under controlled conditions.
AB  - Snatch farrowed, colostrum deprived piglets were inoculated with different
      combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix
      rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following
      virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum,
      all animals were monitored and samples taken for serology, immunohistochemistry
      and qPCR. At 24 dpc all non-vaccinated animals remaining were exhibiting signs of
      post-weaning multi-systemic wasting syndrome which was confirmed by laboratory
      analysis. Details of the study, analysis of samples and performance of the
      candidate vaccines are described.

PMID- 27033925
TI  - Prospective evaluation of Doppler echocardiography, tissue Doppler imaging and
      biomarkers measurement for the detection of doxorubicin-induced cardiotoxicity in
      dogs: A pilot study.
AB  - The purpose of this pilot study was to evaluate the usefulness of selected
      echocardiographic parameters, NT-proBNP and cardiac troponin I (cTnI) in the
      detection of cardiotoxicity in dogs treated with doxorubicin for various
      malignancies. Echocardiographic studies and biomarker measurements were performed
      before each administration of doxorubicin, then 1 and 3 months after completion
      of therapy. Thirteen dogs were included, with a total cumulative dose of
      doxorubicin ranging from 30 to 150 mg/m(2). E/A ratio significantly decreased
      during doxorubicin administration (p=0.047). cTnI level was also significantly
      affected by treatment (p=0.046), increasing above normal at least at one time
      point in 11 of 13 dogs. The results of this pilot study suggest that monitoring
      of left ventricular diastolic function and cTnI level measurement might be useful
      in the early detection of cardiotoxic signs of doxorubicin therapy in dogs.

PMID- 27033926
TI  - Pharmacokinetics of moxidectin in alpacas following administration of an oral or
      subcutaneous formulation.
AB  - The purpose of this study was to evaluate the pharmacokinetics of moxidectin in
      alpacas after single subcutaneous injection of a non-aqueous formulation or oral
      administration of an aqueous drench at 0.2 mg*kg(-1). Plasma moxidectin
      concentrations were measured with reverse phase HPLC, and data analyzed using non
      compartmental methods. Half-life was longer (p=0.02) after subcutaneous
      administration than oral (292+/-170 vs 33+/-39 h). The area under the
      concentration-time curve was greater (p=0.04) following subcutaneous
      administration (1484.8+/-1049.5 h*ng*ml(-1)) than oral (157.6+/-85.9 h*ng*ml(
      1)). The peak concentration (Cmax) was higher and the after subcutaneous
      administration, but the difference was not statistically significant (p=0.18).
      The relative bioavailability of the oral moxidectin to the subcutaneous
      moxidectin was 11%. The data suggest a higher relative bioavailability following
      subcutaneous compared to oral administration. Further studies are needed to
      determine the therapeutic concentrations of moxidectin in alpacas.

PMID- 27033927
TI  - Behavior of plastic and metal ameroid constrictors during in vitro incubation in
      physiologic solutions of varying glucose concentration.
AB  - The objective of this study was to evaluate the influence of ameroid constrictor
      (AC) composition as well as glucose concentration in the surrounding fluid on the
      rate and completeness of AC closure. In a pilot study, four ACs (two metal, two
      plastic) were incubated in a solution containing 100 mg/dL glucose, and in a
      follow-up study, two additional ACs (one metal, one plastic) were incubated in a
      solution of 100 mg/dL glucose and six ACs (three metal, three plastic) were
      incubated in a solution of 50 mg/dL glucose. Dimensions of the ACs were analyzed
      weekly for 57 days. No significant difference was found in the rate or overall
      proportionate closure for either metal versus plastic ACs or ACs incubated in 50
      mg/dL versus 100 mg/dL glucose. As there was no statistically significant
      difference in the proportionate closure of metal and plastic ACs, both types are
      clinically suitable for gradual attenuation of portosystemic shunts in animal
      patients. The lack of a significant difference in rate and completeness of
      closure of ACs incubated in different concentrations of glucose provides evidence
      that the glucose concentration of the surrounding fluid likely does not have a
      significant effect on AC closure. However, a significant difference in the
      proportionate closure of ACs occurred within the first week of the study between
      constrictors incubated in 50 mg/dL glucose and those incubated in 100 mg/dL
      glucose, and additional studies are indicated to determine the significance of
      this early difference in vivo.

PMID- 27033928
TI  - Proteomic and ultrastructural analysis of the effect of a new nitazoxanide-N
      methyl-1H-benzimidazole hybrid against Giardia intestinalis.
AB  - In an effort to develop alternative drugs for the treatment of giardiasis our
      research group has synthesized and evaluated a novel nitazoxanide and N-methyl-1H
      benzimidazole hybrid molecule, named CMC-20. It showed an IC50 of 0.010 MUM on
      Giardia intestinalis, lower than the IC50 values of 0.015, 0.037 and 1.224 MUM
      for nitazoxanide, albendazole and metronidazole, respectively. In addition, we
      report studies carried out on its mechanism of action and effect at the
      ultrastructural level on G. intestinalis. The proteomic analysis of trophozoites
      treated with CMC-20 revealed significant changes in the expression level of
      proteins of the cytoskeleton, alpha and beta tubulin, alpha-1, beta giardin and
      axoneme-associated protein, among other molecules. Ultrastructural studies
      demonstrated that CMC-20 induces morphological changes on the parasite that loses
      its characteristic pear shape. Uncommon large bulbous structure at the flagella
      end, and parasites showing flange membrane bending and a concave depression in
      the ventral region, resembling an encystation process, were also observed. In
      addition, some apoptotic and autophagic-like features, such as membrane blebbing,
      intense vacuolation, chromatin condensation and multilamellar bodies were
      detected. Phosphatidylserine externalization was determined as an apoptotic
      marker by flow cytometry and immunofluorescence microscopy; however, a typical
      ladder-like DNA fragmentation profile was not detected. Although it was found
      that CMC-20 triggers the encystation process, damage to the cyst wall indicates
      loss of viability.

PMID- 27033929
TI  - Relationships between leptin, KiSS-1/GPR54 expression and TSH secretion from
      pituitary cells of pubertal ewes in vitro.
AB  - Kisspeptin and leptin play a crucial role in the puberty of sheep as they
      initiate the activity of hypothalamic-pituitary-ovarian axis. Also hormones of
      thyrotropic axis are probably involved in this process. The aim of study was to
      analyze the impact of leptin on kisspeptin-10 secretion as well as kisspeptin-1
      and G protein-coupled receptor (GPR54) mRNA expression in pituitary cells of
      pubertal ewes in vitro. The influence of kisspeptin on TSH secretion was also
      examined. Cells were cultured in McCoy's 5A medium without hormones; with 10(-10)
      10(-5)M of leptin; with 10(-11)-10(-5)M of kisspeptin-10; with peptide 234 (10(
      7)M, antagonist of GPR54) or 10(-11)-10(-5)M of kisspeptin-10 and peptide 234.
      Then, kisspeptin-10 and TSH secretion as well as KiSS-1 and GPR54 expression were
      analyzed. We found that leptin directly affected kisspeptin-10 secretion and
      kisspeptin-1/GPR54 expression in pituitary cells of pubertal ewes. Kisspeptin-10
      did not change TSH secretion, except exerting a short-term influence after 2h. 

PMID- 27033930
TI  - Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie
      results in PrP(Sc) accumulation in sheep with the PRNP ARQ/ARQ but not the
      ARQ/ARR genotype.
AB  - Scrapie is a transmissible spongiform encephalopathy that can be transmitted
      amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences
      the susceptibility of sheep to the scrapie agent. This study reports the failure
      to detect PrP(Sc) in nervous or lymphoid tissues of Suffolk sheep of the PRNP
      ARQ/ARR genotype after oral inoculation with a U.S. scrapie isolate. Lambs were
      inoculated within the first 24 h of birth with 1 ml of a 10% (wt./vol.) brain
      homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep
      were observed daily throughout the experiment for clinical signs suggestive of
      scrapie until they were necropsied at 86 months post inoculation. Tissues were
      collected for examination by immunohistochemistry and enzyme immunoassay, but all
      failed to demonstrate evidence of scrapie infection. Neonatal sheep of the
      ARQ/ARQ genotype receiving the same inoculum developed scrapie within 24 months.
      Lambs of the ARQ/ARR genotype that received the same inoculum by intracranial
      inoculation develop scrapie with a prolonged incubation period and with abnormal
      prion present within the central nervous system, but not peripheral lymphoid
      tissues. Results of this study suggest that ARQ/ARR sheep are resistant to oral
      infection with the scrapie isolate used even during the neonatal period.

PMID- 27033931
TI  - Dissemination of metal resistance genes among animal methicillin-resistant
      coagulase-negative Staphylococci.
AB  - The use of metals as feed supplement has been recognized as a potential driver
      for co-selection of methicillin-resistant Staphylococcus aureus in pigs. However,
      the prevalence of these determinants in methicillin-resistant coagulase-negative
      staphylococci (MRCoNS) is largely unknown. In this study, a collection of 130
      MRCoNS from pigs and veal calves were investigated for the presence of metal
      resistance genes (czrC, copB, cadD, arsA) associated to SCCmec. Near half of the
      isolates carried metal resistance genes (czrC 5.4%, copB 38.5%, cadD 7.7%, arsA
      26.2%) regardless of their SCCmec type. The increased use of metals in livestock
      animals, especially zinc in pigs in several European countries may co-select for
      methicillin-resistance in several staphylococcal species. 

PMID- 27033932
TI  - Altered expression of p53, but not Rb, is involved in canine prostatic
      carcinogenesis.
AB  - Abnormalities in the retinoblastoma (Rb) and p53 tumour suppressor gene have been
      frequently detected in human and canine cancers, but never investigated in canine
      prostate cancer, considered a good model for the advanced and aggressive androgen
      resistant prostate cancer in men. Therefore, the aim of this study was to
      evaluate the immunohistochemical expression of Rb and p53 in 6 normal canine
      prostates, 15 canine prostates with benign prostatic hyperplasia (BPH) and 10
      prostatic carcinomas (PCs). In all normal samples, p53 was expressed in low
      number of epithelial cells, while a greater number of positive cells were
      observed in BPH and PC. The mean number of positive cells was statistically
      significantly higher in PCs than normal and hyperplastic prostates. A cytoplasmic
      or nucleo-cytoplasmic staining was observed in 5 out of 10 PCs. Rb protein was
      expressed in high number of normal, hyperplastic and neoplastic cells without a
      statistically significant differences. Considering that Rb is frequently lost in
      human prostate cancer, we suggest that Rb is not involved in canine prostatic
      carcinogenesis. On the other hand, the increased expression of p53 that
      corresponds to genetic defects in the p53 gene may be associated with the
      malignant growth of canine prostate cancer, conferring an apoptosis-resistant
      phenotype. 

PMID- 27033933
TI  - Aberrant expression of miR-127, miR-21 and miR-16 in placentas of deceased cloned
      sheep.
AB  - Placental deficiencies are associated with developmental abnormalities of animal
      produced by somatic cell nuclear transfer (SCNT). It is reported that aberrant
      expression of microRNAs (miRNAs) in the common placenta is associated with fetal
      growth restriction and placental deficiencies. However, an understanding of the
      expression and function of miRNAs in the placentas of cloned animal is lacking.
      In this study, we characterized the expression of five growth-associated miRNAs
      (miR-127, miR-16, miR-21, miR-93 and miR-182) in placentas of deceased transgenic
      cloned sheep (deceased group, n=7), live transgenic cloned sheep (live group,
      n=5) and conventionally produced sheep (control group, n=10). Expression levels
      of miR-127 (P<0.01), miR-21 (P<0.01) and miR-16 (P<0.05) were significantly up
      regulated in the placentas of deceased group compared to that of control group.
      In contrast, the expression of these miRNAs was largely normal in the placentas
      of live group, except for the expression of miR-21. Furthermore, we confirmed
      that retrotransposon-like gene (Rtl1), a key gene in placental development, was
      down-regulated by miR-127 as a target in placenta cells. Our results suggested
      that the abnormal expression of miR-127, miR-21 and miR-16 in placentas of
      deceased sheep, through dysregulation of target genes, may result in
      developmental deficiencies of transgenic cloned sheep. 

PMID- 27033934
TI  - Early events of canine herpesvirus 1 infections in canine respiratory and genital
      mucosae by the use of ex vivo models.
AB  - Canine herpesvirus 1 (CaHV-1) causes a systemic disease in newborn puppies,
      kennel cough at all ages and genital lesions in adult dogs. The aim of the
      present study was to elucidate the viral behavior during the early stage of
      infection in respiratory and genital mucosae, the portals of entry for CaHV-1 by
      the use of ex vivo explants. CaHV-1 infected and replicated in respiratory and
      vaginal mucosae in a plaque wise manner. CaHV-1 started to penetrate the basement
      membrane (BM) only after 48 h post inoculation (hpi) in respiratory mucosal
      explants, but already after 24 hpi in vaginal explants. The plaque latitude and
      penetration depth increased over time and both were larger in the vaginal
      explants compared to the respiratory mucosal explants. The canine respiratory and
      genital mucosal explants were suitable to study the early pathogenesis of CaHV-1.
      CaHV-1 showed a better capacity to replicate and invade vaginal mucosa compared
      to respiratory mucosa, based on the latitude and penetration depth of the plaques
      of viral antigen positive cells.

PMID- 27033935
TI  - Polymerization-dependent activation of porcine gammadelta T-cells by
      proanthocyanidins.
AB  - Plant-derived proanthocyanidins (PAC) have been promoted as a natural method of
      improving health and immune function in livestock. It has previously been shown
      that PAC are effective agonists for activating ruminant gammadelta T-cells in
      vitro, however effects on other livestock species are not yet clear. Moreover,
      the fine structural characteristics of the PAC which contribute to this
      stimulatory effect have not been elucidated. Here, we demonstrate activation of
      porcine gammadelta T-cells by PAC via up-regulation of CD25 (IL-2Ralpha) and show
      that 1) activation is dependent on degree of polymerization (DP), with PAC
      fractions containing polymers with mean DP >6 significantly more effective than
      fractions with mean DP <6, whilst flavan-3-ol monomers (the constituent monomeric
      units of PAC) did not induce CD25 expression and 2) both procyanidin and
      prodelphinidin-type PAC are effective agonists. Furthermore, we show that this
      effect of PAC is restricted to the gammadelta T-cell population within porcine
      peripheral mononuclear cells as significant CD25 up-regulation was not observed
      in non gammadelta T-cells, and no activation (via CD80/86 up-regulation) was
      evident in monocytes. Our results show that dietary PAC may contribute to
      enhancement of innate immunity in swine via activation of gammadelta T-cells. 

PMID- 27033936
TI  - Randomized, non-inferiority trial comparing a nitric oxide releasing solution
      with a macrolide antibiotic for control of bovine respiratory disease in beef
      feedlot calves at high-risk of developing respiratory tract disease.
AB  - Nitric oxide, a molecule produced in most mammalian cells, has bactericidal and
      virucidal properties. Nasal instillation of a nitric oxide releasing solution
      (NORS) on arrival at the feedlot was recently reported as non-inferior to a
      parenteral injection of a macrolide antibiotic, tilmicosin, for control of bovine
      respiratory disease (BRD) in cattle at low-to-moderate risk of developing BRD.
      The objective of this study was to evaluate whether NORS was non-inferior to
      tilmicosin for control of BRD in cattle at high-risk of developing BRD (the
      target population for many BRD control programs). High-risk Angus-cross heifers
      (n=840) were randomly allocated to 2 treatment groups on arrival at a feedlot and
      received either NORS or tilmicosin for BRD control. Non-inferiority was assessed
      by calculating the difference in prevalence of heifers diagnosed with BRD during
      the first 40 d after arrival between NORS and tilmicosin treatment groups. The
      non-inferiority margin (delta) was set at 8.5%. Thirty-six and 19% of heifers
      were diagnosed with BRD in the NORS and tilmicosin groups, respectively. Because
      the lower bound of the 2-sided 95% confidence interval (CI) of the difference in
      BRD prevalence between the 2 treatment groups (17%; 95% CI=11-23%) was higher
      than delta, an inferiority of NORS was concluded. Although on-arrival nasal
      administration of NORS can be viewed as a more rational control strategy than
      parental injection of antibiotics, further research is needed to improve NORS
      efficacy before it can be recommended to prevent BRD in high-risk cattle.

PMID- 27033937
TI  - Plasma biomarkers of SIRS and MODS associated with canine babesiosis.
AB  - Canine babesiosis is a tick-borne disease caused by the haemoprotozoan parasites
      of the genus Babesia. Early detection of systemic inflammatory response syndrome
      (SIRS) and multiple organ dysfunction syndrome (MODS) is of major importance in
      clinical practice for providing information about severity and outcomes of the
      disease and therapy. Plasma samples were taken at admission from five dogs with
      uncomplicated babesiosis caused by B. canis canis, five dogs with babesiosis and
      SIRS, five dogs with babesiosis and MODS, and five healthy dogs. After two
      dimensional electrophoresis and capillary reversed - phase liquid chromatography
      coupled online with tandem mass spectrometry, 68 differentially expressed spots
      with level of significance P<0.05 were detected between groups. SIRS in
      babesiosis was characterised by increases in paraoxonase 1 and apoA-I, whereas
      MODS with decrease of complement inhibitors leading to prolonged complement
      activation and decrease of vitamin D binding protein due to haemolysis and
      activation of the coagulation cascade. 

PMID- 27033938
TI  - Immune response, productivity and quality of milk from grazing goats as affected
      by dietary polyunsaturated fatty acid supplementation.
AB  - This study was undertaken to assess how diet supplemented with fish oil and
      linseed improve the immune profile, the production performance, and milk quality
      of grazing goats by a diet supplementation of fish oil or linseed. Twenty-four
      Garganica grazing goats were divided into three groups named control (CON), fish
      oil (FO) and linseed (LIN) according to the fat supplement received in their
      diet. In vivo immune responses were evaluated by monitoring cell-mediated and
      humoral immune responses in order to verify the effects of polyunsaturated fatty
      acids supplementation on goats' health status. Goat milk samples were analysed
      weekly to determine milk chemical composition, fatty acid profile, and somatic
      cell count. Diet based on linseed supplementation (LIN) significantly increased
      milk yield by 30%, milk fat yield by 67%, protein yield by 34%, and casein yield
      by 41% as compared with CON. Fat content increased by 30% in LIN milk as compared
      with CON milk, and by 12% as compared with FO milk. Linseed modified milk fatty
      acid profile; LIN milk showed lower SFA and higher PUFA than FO milk. The
      modified fatty acid composition of LIN milk resulted in lower AI and TI indexes
      than FO and CON milk. Linseed and fish oil administration can reduce humoral
      immunity of goats, but has no effect in their cellular immunity. Dietary linseed
      supplementation in grazing dairy goat supports feeding programs to improve milk
      composition and quality, and a modulation of their immune responses. 

PMID- 27033939
TI  - Correlation of brain Magnetic Resonance Imaging of spontaneously lead poisoned
      bald eagles (Haliaeetus leucocephalus) with histological lesions: A pilot study.
AB  - Six bald eagles with severe, acute lead poisoning based on blood lead values were
      analyzed by Magnetic Resonance Imaging (MRI) of the brain and histopathology. The
      aims of the study were to use MRI to locate brain lesions and correlate the
      changes in MRI signal with the histological character of the lesions at necropsy.
      All of the bald eagles presented with neurologic and non-neurologic signs
      suggestive of severe lead poisoning and had blood lead levels in excess of 1.0
      ppm. Areas of change in image intensity in the brainstem, midbrain and cerebellum
      were detected in the MRI scans. Histopathology confirmed the presence of all
      suspected lesions. The character of the lesions suggested vascular damage as the
      primary insult. MRI was useful for detecting lesions and defining their three
      dimensional distribution and extent. Future studies are needed to evaluate the
      utility of MRI for detection of lesions in less severely lead poisoned eagles and
      determining prognosis for treatment.

PMID- 27033940
TI  - Methanol extract of Nyctanthes arbortristis seeds enhances non-specific immune
      responses and protects Oreochromis mossambicus (Peters) against Aeromonas
      hydrophila infection.
AB  - Immunostimulation using medicinal plant extracts is a promising approach for
      prevention and control of diseases with reference to sustainable fish farming.
      Oreochromis mossambicus, dubbed as aquatic chicken is a cultured fish worldwide
      and a laboratory model organism. Aeromonas hydrophila is one of the major
      bacterial pathogens in fish farming that causes huge loss to aquaculture
      industries. In this study, we investigated the efficacy of methanol extract of
      Nyctanthes arbortristis seeds on disease resistance of O. mossambicus against
      live virulent A. hydrophila. We also investigated its effect on the non-specific
      immune parameters such as serum lysozyme, myeloperoxidase, antiprotease and
      specific immune parameters in terms of specific serum antibody titres assayed by
      bacterial agglutination test. Our studies indicate that intra-peritoneal
      administration of 20mg/kg methanol extract increases the Relative Percent
      Survival (RPS) of O. mossambicus challenged with LD80 of A. hydrophila. Further,
      both non-specific and specific immune parameters were enhanced by the methanol
      extract. Further experiments at molecular levels in the laboratory and also
      efficacy testing at field level are essential before applying this plant product
      in aquaculture industry. 

PMID- 27033941
TI  - Molecular analysis of leptospires from serogroup Sejroe obtained from
      asymptomatic cattle in Rio de Janeiro - Brazil reveals genetic proximity to
      serovar Guaricura.
AB  - Bovine leptospirosis causes substantial reproductive failure in cattle, mainly
      due to infections with serovar (sv) Hardjo infection. Notwithstanding, other
      serovars from the serogroup (sg) Sejroe could also have important roles in bovine
      leptospirosis. The objective was to investigate genetic diversity of serogroup
      Sejroe isolates obtained from asymptomatic cattle in the state of Rio de Janeiro,
      Brazil. Urine and vaginal fluid (VF) were collected from clinically healthy
      cattle immediately after slaughter. Five isolates were recovered and
      characterized (serogrouping) as belonging to sg Sejroe. Sequencing of rrs and
      secY genes further identified them as Leptospira santarosai. Analysis of secY
      sequences indicated a high level of sequence homology to sv Guaricura strains.
      Based on culture and sequence data, we inferred that other members of sg Sejroe
      may be important in bovine leptospiral infection, particularly genotypes of L.
      santarosai serovar Guaricura. 

PMID- 27033942
TI  - Psychiatric disorders in persons aged 60 years or older treated as inpatients ou
      outpatients in hospitals in Togo: epidemiological, clinical, and therapeutic
      aspects.
AB  - The objective of this study was to describe the social, demographic, and clinical
      profile of inpatients and outpatients 60 years or older treated for psychiatric
      disorders. This descriptive and analytic retrospective study took place at the
      inpatient and outpatient psychiatry departments at two university hospital
      centers in Lome: Campus and Sylvanus Olympio of Lome. It included patients aged
      60 years or older seen during the 10-year period 2004-2013 who met ICD-10
      diagnostic criteria for psychiatric disease. This series comprised 224 patients
      with a mean age of 67.6 +/- 7.37 years (range: 60-97). Insomnia (16%),
      hallucinations (8.53%), and somatic complaints (7.73%) were the most frequent
      motives for consultation. Family or friends accompanied 80.36% of these patients
      to the consultation. Among the patients, 66.96% were aware of their disorder, and
      60.71% showed an adherence to treatment. The main diagnoses were depressive
      disorders (25.89%) and various forms of dementia (23.66%) The prevention of
      depression disorders in this population requires real work on mourning. 

PMID- 27033943
TI  - Mutational analysis of structural elements in a class-I cyclic di-GMP riboswitch
      to elucidate its regulatory mechanism.
AB  - The Vc2 riboswitch possesses an aptamer domain belonging to the class-I c-di-GMP
      riboswitch family. This domain has been analysed and the molecular mechanism by
      which it recognizes the c-di-GMP ligand has been elucidated. On the other hand,
      the regulatory mechanism of the full-length Vc2 riboswitch to control its
      downstream open reading frame (ORF) remains largely unknown. In this study, we
      performed in vivo reporter assays and in vitro biochemical analyses of the full
      length riboswitch and its aptamer domain. We evaluated the results of in vivo and
      in vitro analyses to elucidate the regulatory mechanism of the Vc2 riboswitch.
      The present results suggest that recognition of c-di-GMP ligand by the Vc2
      riboswitch aptamer domain downregulates expression of its downstream ORF
      primarily at the translational level. 

PMID- 27033944
TI  - Long noncoding RNA POU6F2-AS2 is associated with oesophageal squamous cell
      carcinoma.
AB  - Oesophageal carcinoma is one of the most lethal cancer types in the world,
      especially in some part of China. Oesophageal squamous cell carcinoma (OSCC) is a
      major subtype, which has been shown to be associated with unhealthy diet habit,
      smoking, environmental carcinogens etc. The OSCC often progress slowly, however,
      it is often diagnosed at an advanced stage. Thus it is imperative to elucidate
      the molecular mechanisms involved in the initiation and progression of OSCC. Long
      noncoding RNAs (lncRNA) has emerged as a novel functional player transcribed from
      the genome. Here, we describe a novel lncRNA POU6F2-AS2 specifically expressed in
      OSCC. POU6F2-AS2 is involved in the DNA damage response and regulates cells
      survival after ionizing radiation. POU6F2-AS2 interacts with Ybx1 protein and
      regulates its chromatin localization. Our current study represents the first
      description of an OSCC associated lncRNA that modulates DNA repair.

PMID- 27033946
TI  - Author's reply to Banda and Lokugamage.

PMID- 27033947
TI  - Cryptic diversity and symbiont interactions in rock-posy lichens.
AB  - Identifying factors that influence species interactions is central to research in
      symbiotic systems. While lichens represent iconic models of symbiosis and play
      important roles in understanding the biology of symbiotic interactions, patterns
      of interactions in lichen symbionts and mechanisms governing these relationships
      are not well characterized. This is due, in part to the fact that current
      taxonomic approaches for recognizing diversity in lichen symbionts commonly fail
      to accurately reflect actual species diversity. In this study, we employed DNA
      based approaches to circumscribed candidate species-level lineages in rock-posy
      lichen symbionts (mycobiont=Rhizoplaca s. lat. species; photobiont=Trebouxia
      species). Our results revealed a high degree of cryptic diversity in both the
      myco- and photobionts in these lichens. Using the candidate species circumscribed
      here, we investigated the specificity of the symbionts toward their partners and
      inferred the relative importance of various factors influencing symbiont
      interactions. Distinct mycobiont species complexes, ecozones, and biomes are
      significantly correlated with the occurrence of photobiont OTUs, indicating that
      complex interactions among mycobiont lineages, ecogeography, and microhabitat
      determine interactions between photobionts and their mycobionts in lichen
      symbiosis. One-to-one specificity between mycobiont and photobiont species was
      not found, with the exception of R. maheui that associated with a single
      Trebouxia OTU that was not found with other Rhizoplaca s. lat. species. We
      estimated the most recent common ancestor of the core Rhizoplaca group at c.
      62.5Ma, similar in age to the diverse parmelioid core group in the well-studied
      family Parmeliaceae. However, in contrast to Parmeliaceae, species in Rhizoplaca
      were found to associate with a narrow range of photobionts. Our study provides
      important perspectives into species diversity and interactions in iconic lichen
      symbiotic systems and establishes a valuable framework for continuing research
      into rock-posy lichens.

PMID- 27033948
TI  - The evolutionary history of the E2F and DEL genes in Viridiplantae.
AB  - The E2 promoter binding factor (E2F) proteins are present in almost all
      eukaryotic organisms and are essential to control several processes, such as the
      cell cycle progression, cell division, DNA replication, and apoptosis. The E2F
      family comprises two different types of proteins: the typical E2Fs and atypical
      E2Fs, which differ structurally and have specific functions. The E2F gene family
      was described for the first time in plants in 1999, and since then several
      studies have focused on the functional aspects, but the evolutionary history of
      this gene family is still unknown. Here, we investigated the evolutionary history
      of the E2F gene family in plants. Our findings suggest that E2F proteins arose
      early after the emergence of the eukaryotic species, while DEL proteins appear to
      have arisen before the metazoan and plants origin probably through a partial
      duplication of an ancient E2F protein. Our data also suggest that E2Fs activators
      and repressors appeared twice during evolution, once in the metazoan lineage and
      again in the embryophyte lineage.

PMID- 27033945
TI  - Optic disk drusen in children.
AB  - Optic disk drusen occur in 0.4% of children and consist of acellular
      intracellular and extracellular deposits that often become calcified over time.
      They are typically buried early in life and generally become superficial, and
      therefore visible, later in childhood, at the average age of 12 years. Their main
      clinical significance lies in the ability of optic disk drusen, particularly when
      buried, to simulate true optic disk edema. Misdiagnosing drusen as true disk
      edema may lead to an invasive and unnecessary workup for elevated intracranial
      pressure. Ancillary testing, including ultrasonography, fluorescein angiography,
      fundus autofluorescence, and optical coherence tomography, may aid in the correct
      diagnosis of optic disk drusen. Complications of optic disk drusen in children
      include visual field defects, hemorrhages, choroidal neovascular membrane,
      nonarteritic anterior ischemic optic neuropathy, and retinal vascular occlusions.
      Treatment options for these complications include ocular hypotensive agents for
      visual field defects and intravitreal anti-vascular endothelial growth factor
      agents for choroidal neovascular membranes. In most cases, however, children with
      optic disk drusen can be managed by observation with serial examinations and
      visual field testing once true optic disk edema has been excluded.

PMID- 27033949
TI  - Phylogenetic distribution and evolutionary pattern of an alpha-proteobacterial
      small RNA gene that controls polyhydroxybutyrate accumulation in Sinorhizobium
      meliloti.
AB  - It has become clear that sRNAs play relevant regulatory functions in bacteria.
      However, a comprehensive understanding of their biological roles considering
      evolutionary aspects has not been achieved for most of them. Thus, we have
      characterized the evolutionary and phylogenetic aspects of the Sinorhizobium
      meliloti mmgR gene encoding the small RNA MmgR, which has been recently reported
      to be involved in the regulation of polyhydroxybutyrate accumulation in this
      bacterium. We constructed a covariance model from a multiple sequence and
      structure alignment of mmgR close homologs that allowed us to extend the search
      and to detect further remote homologs of the sRNA gene. From our results, mmgR
      seemed to evolve from a common ancestor of the alpha-proteobacteria that diverged
      from the order of Rickettsiales. We have found mmgR homologs in most current
      species of alpha-proteobacteria, with a few exceptions in which genomic reduction
      events or gene rearrangements seem to explain its absence. Furthermore, a strong
      microsyntenic relationship was found between a large set of mmgR homologs and
      homologs of a gene encoding a putative N-formyl glutamate amidohydrolase (NFGAH)
      that allowed us to trace back the evolutionary path of this group of mmgR
      orthologs. Among them, structure and sequence traits have been completely
      conserved throughout evolution, namely a Rho-independent terminator and a 10-mer
      (5'-UUUCCUCCCU-3') that is predicted to remain in a single-stranded region of the
      sRNA. We thus propose the definition of the new family of alpha-proteobacterial
      sRNAs alphar8, as well as the subfamily alphar8s1 which encompass S. meliloti
      mmgR orthologs physically linked with the downstream open reading frame encoding
      a putative NFGAH. So far, mmgR is the trans-encoded small RNA with the widest
      phylogenetic distribution of well recognized orthologs among alpha
      proteobacteria. Expression of the expected MmgR transcript in rhizobiales other
      than S. meliloti (Sinorhizobium fredii, Rhizobium leguminosarum and Rhizobium
      etli) was confirmed by Northern blot. These findings will contribute to the
      understanding of the biological role(s) of mmgR in the alpha-proteobacteria.

PMID- 27033950
TI  - A multilocus molecular phylogeny of Fasciolariidae (Neogastropoda: Buccinoidea).
AB  - The neogastropod family Fasciolariidae Gray, 1853 - tulips, horse-conchs,
      spindles, etc., comprises important representatives of tropical and subtropical
      molluscan assemblages, with over 500 species in the subfamilies Fasciolariinae
      Gray, 1853, Fusininae Wrigley, 1927 and Peristerniinae Tryon, 1880. Fasciolariids
      have had a rather complicated taxonomical history, with several genus names for a
      long time used as waste baskets to group many unrelated species; based on shell
      characters, recent taxonomic revisions have, however, began to set some order in
      its taxonomy. The present work is the first molecular approach to the phylogeny
      of Fasciolariidae based on a multigene dataset, which provides support for
      fasciolariids, an old group with a fossil record dating back to the Cretaceous.
      Molecular markers used were the mitochondrial genes 16S rRNA and cytochrome c
      oxidase subunit I, and the nuclear genes 18S rRNA, 28S rRNA and histone H3,
      sequenced for up to 116 ingroup taxa and 17 outgroups. Phylogenetic analyses
      revealed monophyly of Dolicholatirus Bellardi, 1884 and Teralatirus Coomans,
      1965, however it was not possible to discern if the group is the sister clade to
      the remaining fasciolariids; the latter, on the other hand, proved monophyletic
      and contained highly supported groups. A first split grouped fusinines and
      Pseudolatirus Bellardi, 1884; a second split grouped the peristerniine genera
      Peristernia Morch, 1852 and Fusolatirus Kuroda and Habe, 1971, while the last
      group comprised fasciolariines and the remaining peristerniines. None of these
      clades correspond to the present-day accepted circumscription of the three
      recognized subfamilies.

PMID- 27033951
TI  - Reassessing the phylogenetic position of the epizoic earwigs (Insecta:
      Dermaptera).
AB  - Dermaptera is a relatively small order of free-living insects that typically feed
      on detritus and other plant material. However, two earwig lineages - Arixeniidae
      and Hemimeridae - are epizoic on Cheiromeles bats and Beamys and Cricetomys rats
      respectively. Both of these epizoic families are comprised of viviparous species.
      The monophyly of these epizoic lineages and their placement within dermapteran
      phylogeny has remained unclear. A phylogenetic analyses was performed on a
      diverse sample of 47 earwig taxa for five loci (18S rDNA, 28S rDNA, COI, Histone
      3, and Tubulin Alpha I). Our results support two independent origins of the
      epizoic lifestyle within Dermaptera, with Hemimeridae and Arixeniidae each
      derived from a different lineage of Spongiphoridae. Our analyses places Marava, a
      genus of spongiphorids that includes free-living but viviparous earwigs, as
      sister group to Arixeniidae, suggesting that viviparity evolved prior to the
      shift to the epizoic lifestyle. Additionally, our results support the monophyly
      of Forficulidae and Chelisochidae and the paraphyly of Labiduridae,
      Pygidicranidae, Spongiphoridae, and Anisolabididae.

PMID- 27033952
TI  - Impact of aging on mitochondrial function in cardiac and skeletal muscle.
AB  - Both skeletal muscle and cardiac muscle are subject to marked structural and
      functional impairment with aging and these changes contribute to the reduced
      capacity for exercise as we age. Since mitochondria are involved in multiple
      aspects of cellular homeostasis including energetics, reactive oxygen species
      signaling, and regulation of intrinsic apoptotic pathways, defects in this
      organelle are frequently implicated in the deterioration of skeletal and cardiac
      muscle with aging. On this basis, the purpose of this review is to evaluate the
      evidence that aging causes dysfunction in mitochondria in striated muscle with a
      view towards drawing conclusions about the potential of these changes to
      contribute to the deterioration seen in striated muscle with aging. As will be
      shown, impairment in respiration and reactive oxygen species emission with aging
      are highly variable between studies and seem to be largely a consequence of
      physical inactivity. On the other hand, both skeletal and cardiac muscle
      mitochondria are more susceptible to permeability transition and this seems a
      likely cause of the increased recruitment of mitochondrial-mediated pathways of
      apoptosis seen in striated muscle. The review concludes by examining the role of
      degeneration of mitochondrial DNA versus impaired mitochondrial quality control
      mechanisms in the accumulation of mitochondria that are sensitized to
      permeability transition, whereby the latter mechanism is favored as the most
      likely cause.

PMID- 27033953
TI  - Cytoplasmic localization of Nrf2 promotes colorectal cancer with more aggressive
      tumors via upregulation of PSMD4.
AB  - Differences in subcellular localization of Nuclear factor (erythroid-derived 2)
      like 2 (Nrf2) have been associated with poor outcomes in human cancers. However,
      the prognostic value of subcellular localization of Nrf2 in colorectal cancer and
      the underlying mechanism in tumor invasion remain unknown. We enrolled tumors
      from colorectal patients to evaluate Nrf2, NQO1, and HO-1 expression by
      immunohistochemistry. NQO1 and HO-1 positive tumors showed nearly complete
      expression of Nrf2 in the nucleus and/or showed partial expression in the
      nucleus/cytoplasm (nNrf2); however, tumors negative for NQO1 and HO-1 showed
      almost complete expression of Nrf2 in the cytoplasm and/or partial expression in
      the nucleus/cytoplasm (cNrf2). Kaplan-Meier and Cox regression analysis indicated
      poorer overall survival in patients with cNrf2 tumors than with nNrf2 tumors.
      Cell models provided evidence that cNrf2, rather than nNrf2, was responsible for
      cell invasion and soft agar growth triggered by activation of the NF
      kappaB/AKT/beta-catenin cascade. Mechanistically, cNrf2 persistently increased
      PSMD4 expression by the HIF1alpha/beta-catenin axis, whereas PSMD4 reciprocally
      enhanced Nrf2 nuclear export by increasing CRM1 expression through p53
      degradation. The mechanistic action of the cell model was further confirmed with
      a nude mouse animal model in which xenograft tumors induced by cNrf2 were nearly
      completely suppressed by the proteasomal inhibitor carfilzomib or the beta
      catenin inhibitor XAV939. We therefore suggest that PSMD4 or beta-catenin might
      be potential targets for suppressing tumor aggressiveness, and consequently,
      improving outcomes in patients whose tumors express cNrf2.

PMID- 27033954
TI  - MicroRNA-mediated regulation of glutathione and methionine metabolism and its
      relevance for liver disease.
AB  - The discovery of the microRNA (miRNA) family of small RNAs as fundamental
      regulators of post-transcriptional gene expression has fostered research on their
      importance in every area of biology and clinical medicine. In the particular area
      of liver metabolism and disease, miRNAs are gaining increasing importance. By
      focusing on two fundamental hepatic biosynthetic pathways, glutathione and
      methionine, we review recent advances on the comprehension of the role of miRNAs
      in liver pathophysiology and more specifically of models of hepatic
      cholestasis/fibrosis and hepatocellular carcinoma.

PMID- 27033955
TI  - Key role of lattice symmetry in the metal-insulator transition of NdNiO3 films.
AB  - Bulk NdNiO3 exhibits a metal-to-insulator transition (MIT) as the temperature is
      lowered that is also seen in tensile strained films. In contrast, films that are
      under a large compressive strain typically remain metallic at all temperatures.
      To clarify the microscopic origins of this behavior, we use position averaged
      convergent beam electron diffraction in scanning transmission electron microscopy
      to characterize strained NdNiO3 films both above and below the MIT temperature.
      We show that a symmetry lowering structural change takes place in case of the
      tensile strained film, which undergoes an MIT, but is absent in the compressively
      strained film. Using space group symmetry arguments, we show that these results
      support the bond length disproportionation model of the MIT in the rare-earth
      nickelates. Furthermore, the results provide insights into the non-Fermi liquid
      phase that is observed in films for which the MIT is absent. 

PMID- 27033956
TI  - Effectiveness of implementation strategies in improving physician adherence to
      guideline recommendations in heart failure: a systematic review protocol.
AB  - INTRODUCTION: The uptake of Clinical Practice Guideline (CPG) recommendations
      that improve outcomes in heart failure (HF) remains suboptimal. We will conduct a
      systematic review to identify implementation strategies that improve physician
      adherence to class I recommendations, those with clear evidence that benefits
      outweigh the risks. We will use American, Canadian and European HF guidelines as
      our reference. METHODS AND ANALYSIS: We will conduct a literature search in the
      databases of MEDLINE, EMBASE, HEALTHSTAR, CINAHL, Cochrane Library, Campbell
      Collaboration, Joanna Briggs Institute Evidence Based Practice, Centre for
      Reviews and Dissemination and Evidence Based Practice Centres. We will include
      prospective studies evaluating implementation interventions aimed at improving
      uptake of class I CPG recommendations in HF. We will extract data in duplicate.
      We will classify interventions according to their level of application (ie,
      provider, organisation, systems level) and common underlying characteristics (eg,
      education, decision-support, financial incentives) using the Cochrane Effective
      Practice and Organisation of Care Taxonomy. We will assess the impact of the
      intervention on adherence to the CPGs. Outcomes will include proportion of
      eligible patients who were: prescribed a CPG-recommended pharmacological
      treatment; referred for device consideration; provided self-care education at
      discharge; and provided left ventricular function assessment. We will include
      clinical outcomes such as hospitalisations, readmissions and mortality, if data
      is available. We will identify the common elements of successful and failing
      interventions, and examine the context in which they were applied, using the
      Process Redesign contextual framework. We will synthesise the results narratively
      and, if appropriate, will pool results for meta-analysis. DISCUSSION AND
      DISSEMINATION: In this review, we will assess the impact of implementation
      strategies and contextual factors on physician adherence to HF CPGs. We will
      explore why some interventions may succeed in one setting and fail in another. We
      will disseminate our findings through briefing reports, publications and
      presentations. TRIAL REGISTRATION NUMBER: CRD42015017155.

PMID- 27033957
TI  - Temperature measurements with a temporal scanner: systematic review and meta
      analysis.
AB  - OBJECTIVES: Systematic review and meta-analysis on the diagnostic accuracy of
      temporal artery thermometers (TAT). DESIGN: Systematic review and meta-analysis.
      The index test consisted of temperature measurement with TAT. The reference test
      consisted of an estimation of core temperature. PARTICIPANTS: Clinical patients
      as well as healthy participants, with or without fever. INTERVENTIONS: Literature
      search in PubMed, Embase, Cinahl and Web of Science. Three reviewers selected
      articles for full-text reading after which a further selection was made. Risk of
      bias was assessed with QUADAS-2. Pooled difference and limits of agreement (LoA)
      were estimated with an inverse variance weighted approach. Subgroup and
      sensitivity analyses were performed. Sensitivity and specificity were estimated
      using hierarchical models. Quality of evidence was assessed according to the
      GRADE system. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was
      measurement accuracy expressed as mean difference +/- 95% LoA. A secondary
      outcome was sensitivity and specificity to detect fever. If tympanic thermometers
      were assessed in the same population as TAT, these results were recorded as well.
      RESULTS: 37 articles comprising 5026 participants were selected. Pooled
      difference was -0.19  degrees C (95% LoA -1.16 to 0.77  degrees C), with moderate
      quality of evidence. Pooled sensitivity was 0.72 (95% CI 0.61 to 0.81) with a
      specificity of 0.94 (95% CI 0.87 to 0.97). The subgroup analysis revealed a trend
      towards underestimation of the temperature for febrile patients. There was a
      large heterogeneity among included studies with wide LoA which reduced the
      quality of evidence. CONCLUSIONS: TAT is not sufficiently accurate to replace one
      of the reference methods such as rectal, bladder or more invasive temperature
      measurement methods. The results are, however, similar to those with tympanic
      thermometers, both in our meta-analysis and when compared with others. Thus, it
      seems that TAT could replace tympanic thermometers with the caveat that both
      methods are inaccurate. TRIAL REGISTRATION NUMBER: CRD42014008832.

PMID- 27033958
TI  - Intravesical administration of combined hyaluronic acid (HA) and chondroitin
      sulfate (CS) for the treatment of female recurrent urinary tract infections: a
      European multicentre nested case-control study.
AB  - OBJECTIVES: To compare the clinical effectiveness of the intravesical
      administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus
      current standard management in adult women with recurrent urinary tract
      infections (RUTIs). SETTING: A European Union-based multicentre, retrospective
      nested case-control study. PARTICIPANTS: 276 adult women treated for RUTIs
      starting from 2009 to 2013. INTERVENTIONS: Patients treated with either
      intravesical administration of HA+CS or standard of care
      (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). PRIMARY AND
      SECONDARY OUTCOME MEASURES: The primary outcome was occurrence of
      bacteriologically confirmed recurrence within 12 months. Secondary outcomes were
      time to recurrence, total number of recurrences, health-related quality of life
      and healthcare resource consumption. Crude and adjusted results for unbalanced
      characteristics are presented. RESULTS: 181 patients treated with HA+CS and 95
      patients treated with standard of care from 7 centres were included. The crude
      and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and
      0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms
      of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to
      1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)).
      The benefit of intravesical HA+CS therapy improves when the number of
      instillations is >= 5. CONCLUSIONS: Our results show that bladder instillations
      of combined HA+CS reduce the risk of bacteriologically confirmed recurrences
      compared with the current standard management of RUTIs. Total incidence rates and
      hazard rates were instead non-significantly different between the 2 groups after
      adjusting for unbalanced factors. In contrast to what happens with antibiotic
      prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over
      time. TRIAL REGISTRATION NUMBER: NCT02016118.

PMID- 27033959
TI  - Utero-placental vascularisation in normal and preeclamptic and intra-uterine
      growth restriction pregnancies: third trimester quantification using 3D power
      Doppler with comparison to placental vascular morphology (EVUPA): a prospective
      controlled study.
AB  - INTRODUCTION: Preeclampsia (PE) and intra-uterine growth restriction (IUGR) are
      two major pregnancy complications related to chronic utero-placental
      hypoperfusion. Three-dimensional power Doppler (3DPD) angiography has been used
      for the evaluation of utero-placental vascularisation and three vascular indices
      have been calculated: the vascularisation index (VI), flow index (FI) and
      vascularisation-FI (VFI). However, several technical endpoints hinder the
      clinical use of 3DPD as physical characteristics and machine settings may affect
      3DPD indices, and so its clinical significance is not yet clear. OBJECTIVES: The
      primary objective is to better understand the clinical significance of 3DPD
      indices by evaluating the relationship between these indices and placental
      morphometry. Secondary objectives are (i) to determine the impact of machine
      settings and physical characteristics on 3DPD indices, and (ii) to evaluate
      physio-pathological placental vascularisation patterns. METHODS AND ANALYSIS:
      This is a prospective controlled study. We expect to include 112 women: 84 with
      normal pregnancies and 28 with PE and/or IUGR (based on our former cohort study
      on 3DPD indices for PE and/or IUGR prediction (unpublished data)). Within 72 h
      before planned or semi-urgent caesarean section, utero-placental 3DPD images with
      five different machine settings will be acquired. Placentas will be collected and
      examined after surgery and stereological indices (volume density, surface
      density, length density) calculated. The 3DPD indices (VI, FI and VFI) of the
      placenta and adjacent myometrium will be calculated. Correlation between Doppler
      and morphological indices will be evaluated by Pearson or Spearman tests.
      Agreement between 3DPD indices and morphological indices will be assessed by
      Bland and Altman plots. The impact of Doppler settings and maternal
      characteristics on 3DPD indices will be evaluated with a multivariate linear
      regression model. ETHICS: The study and related consent forms have been approved
      by the French Ethics Committee (CPP, Comite de Protection des Personnes) Est III
      on 4 March 2014.

PMID- 27033960
TI  - Prevalence of multimorbidity and its association with outcomes in older emergency
      general surgical patients: an observational study.
AB  - OBJECTIVES: Multimorbidity is the presence of 2 or more medical conditions. This
      increasingly used assessment has not been assessed in a surgical population. The
      objectives of this study were to assess the prevalence of multimorbidity and its
      association with common outcome measures. DESIGN: A cross-sectional observational
      study. SETTING: A UK-based multicentre study, included participants between July
      and October 2014. PARTICIPANTS: Consecutive emergency (non-elective) general
      surgical patients admitted to hospital, aged over 65 years. OUTCOME MEASURES: The
      outcome measures were (1) the prevalence of multimorbidity and (2) the
      association between multimorbidity and frailty; the rate and severity of surgery;
      length of hospital stay; readmission to hospital within 30 days of discharge; and
      death at 30 and 90 days. RESULTS: Data were collected on 413 participants aged 65
      98 years (median 77 years, (IQR (70-84)). 51.6% (212/413) participants were
      women. Multimorbidity was present in 74% (95% CI 69.7% to 78.2%) of the
      population and increased with age (p<0.0001). Multimorbidity was associated with
      increasing frailty (p for trend <0.0001). People with multimorbidity underwent
      surgery as often as those without multimorbidity, including major surgery
      (p=0.03). When comparing multimorbid people with those without multimorbidity, we
      found no association between length of hospital stay (median 5 days, IQR (1-54),
      vs 6 days (1-47), (p=0.66)), readmission to hospital (64 (21.1%) vs 18 (16.8%)
      (p=0.35)), death at 30 days (14 (4.6%) vs 6 (5.6%) (p=0.68)) or 90-day mortality
      (28 (9.2%) vs 8 (7.6%) (p=0.60)). CONCLUSIONS AND IMPLICATIONS: Multimorbidity is
      common. Nearly three-quarters of this older emergency general surgical population
      had 2 or more chronic medical conditions. It was strongly associated with age and
      frailty, and was not a barrier to surgical intervention. Multimorbidity showed no
      associations across a range of outcome measures, as it is currently defined.
      Multimorbidity should not be relied on as a useful clinical tool in guidelines or
      policies for older emergency surgical patients.

PMID- 27033962
TI  - Resident reflections on end-of-life education: a mixed-methods study of the 3
      Wishes Project.
AB  - OBJECTIVE: The objectives of this study were to describe residents' experiences
      with end-of-life (EOL) education during a rotation in the intensive care unit
      (ICU), and to understand the possible influence of the 3 Wishes Project. DESIGN:
      We enrolled dying patients, their families and 1-3 of their clinicians in the 3
      Wishes Project, eliciting and honouring a set of 3 wishes to bring peace to the
      final days of a critically ill patient's life, and ease the grieving process for
      families. We conducted semistructured interviews with 33 residents who had cared
      for 50 dying patients to understand their experiences with the project.
      Interviews were recorded, transcribed verbatim, then analysed using a qualitative
      descriptive approach. SETTING: 21-bed medical surgical ICU in a tertiary care,
      university-affiliated hospital. RESULTS: 33 residents participated from internal
      medicine (24, 72.7%), anaesthesia (8, 24.2%) and laboratory medicine (1, 3.0%)
      programmes in postgraduate years 1-3. 3 categories and associated themes emerged.
      (1) EOL care is a challenging component of training in that (a) death in the ICU
      can invoke helplessness, (b) EOL education is inadequate, (c) personal
      connections with dying patients is difficult in the ICU and (d) EOL skills are
      valued by residents. (2) The project reframes the dying process for residents by
      (a) humanising this aspect of practice, (b) identifying that family engagement is
      central to the dying process, (c) increasing emotional responsiveness and (d)
      showing that care shifts, not stops. (3) The project offers experiential
      education by (a) intentional role modelling, (b) facilitating EOL dialogue, (c)
      empowering residents to care in a tangible way and (d) encouraging reflection.
      CONCLUSIONS: For residents, the 3 Wishes Project integrated many forms of active
      learning for residents. Practice-based rather than classroom-based programmes may
      engage trainees to develop EOL skills transferable to other settings.

PMID- 27033961
TI  - A multicenter randomised, 1-year comparative effectiveness, parallel-group trial
      protocol of a physical therapy approach compared to corticosteroid injection on
      pain and function related to knee osteoarthritis (PTA Trial)
AB  - INTRODUCTION: Corticosteroid injections (CSIs) are commonly used as an initial or
      a primary intervention for knee osteoarthritis (OA). Consistent evidence
      indicates CSIs offer symptom relief with conflicting reports regarding long-term
      efficacy. Physical therapy (PT) offers a non-invasive alternative. There is
      moderate evidence suggesting short-term and long-term symptom relief and
      functional improvement with PT interventions. Patients with knee OA are more
      commonly prescribed CSI than PT prior to total joint replacement.
      UnitedHealthcare and Military Health System data show substantially more total
      knee replacement patients receive preoperative CSI than PT. There are no studies
      comparing CSI to a PT approach in individuals with knee OA. The primary objective
      of this study is to compare the effectiveness of CSI to PT in individuals with
      knee OA at 1, 2 and 12 months. METHODS AND ANALYSIS: We plan to recruit 156
      participants meeting established knee OA criteria. Following informed consent,
      participants will be randomised to receive either CSI or PT. All participants
      will receive instruction on recommended exercise and weight control strategies
      plus usual medical care. The CSI intervention consisting of 3 injections and the
      PT intervention consisting of 8-12 sessions will be spaced over 12 months.
      Measures of the dependent variables (DVs) will occur at baseline, 4 weeks, 8
      weeks, 6 months and 12 months post enrolment. This pragmatic, randomised clinical
      trial will be a mixed-model 2*5 factorial design. The independent variables are
      treatment (CSI and PT) and time with five levels from baseline to 1 year. The
      primary DV is the Western Ontario & McMaster Universities Arthritis Index
      (WOMAC). We will also compare healthcare utilisation between the 2 groups. ETHICS
      AND DISSEMINATION: The protocol was approved by the Madigan Army Medical Center
      Institutional Review Board. The authors intend to publish the results in a peer
      reviewed source. TRIAL REGISTRATION NUMBER: NCT01427153.

PMID- 27033963
TI  - Development and validation of a 21-item challenges to stopping smoking (CSS-21)
      scale.
AB  - OBJECTIVE: Identification of challenges associated with quitting and overcoming
      them may improve cessation outcomes. This study describes the development and
      initial validation of a scale for measuring challenges to stopping smoking.
      METHODS: The item pool was generated from empirical and theoretical literature
      and existing scales, expert opinion and interviews with smokers and ex-smokers.
      The questionnaire was administered to smokers and recent quitters who
      participated in a hospital-based smoking cessation trial. Exploratory factor
      analysis was performed to identify subscales in the questionnaire. Internal
      consistency, validity and robustness of the subscales were evaluated. RESULTS: Of
      a total of 182 participants with a mean age of 55 years (SD 12.8), 128 (70.3%)
      were current smokers and 54 (29.7%) ex-smokers. Factor analysis of the 21-item
      questionnaire resulted in a 2-factor solution representing items measuring
      intrinsic (9 items) and extrinsic (12 items) challenges. This structure was
      stable in various analyses and the 2 factors accounted for 50.7% of the total
      variance of the polychoric correlations between the items. Internal consistency
      (Cronbach's alpha) coefficients for the intrinsic and extrinsic subscales were
      0.86 and 0.82, respectively. Compared with ex-smokers, current smokers had a
      higher mean score (+/- SD) for intrinsic (24.0 +/- 6.4 vs 20.5 +/- 7.4, p=0.002)
      and extrinsic subscales (22.3 +/- 7.5 vs 18.6 +/- 6.0, p=0.001). CONCLUSIONS:
      Initial evaluation suggests that the 21-item challenges to stopping smoking scale
      is a valid and reliable instrument that can be used in research and clinical
      settings to assess challenges to stopping smoking.

PMID- 27033964
TI  - Surgical outcomes in children with primary congenital glaucoma: a 20-year
      experience.
AB  - PURPOSE: To describe demographic criteria of primary congenital glaucoma (PCG)
      subjects and to evaluate the surgical outcomes of children who underwent angle
      surgery over a 20-year period. METHODS: This is a retrospective study of patients
      diagnosed with PCG who underwent trabeculotomy, trabeculectomy, or combined
      trabeculotomy-trabeculectomy (CTT). The surgery was considered to be successful
      if intraocular pressure (IOP) was 21 mm Hg or less with or without treatment.
      RESULTS: A total of 148 eyes (85 patients) were included in the study. The
      majority of the patients were younger than 6 months of age (78.9%), with a median
      age of 2 months. Sex distribution was relatively even between girls and boys
      (45:40) (53%/47%). Bilateral disease was seen in 63 patients (74%). The overall
      success rate was achieved in 80.4%. The majority of the eyes needed only one
      surgery (105 [70.9%]), 34 eyes (23.0%) needed 2 surgeries, and 7 eyes (4.7%) had
      3 surgeries. There was no statistically significant difference in success rate
      between types of surgery and number of performed procedures. A progressive
      decline in success rate over time was evident, as success rate dropped from 96.6%
      at 5 months to less than 50% after 11 years of follow-up. CONCLUSIONS: Excellent
      IOP control can be achieved in a majority of patients with equally effective
      results from all 3 surgical procedures. The surgical outcome of PCG was more
      favorable in infants presenting before the age of 6 months. Adjuvant topical
      antiglaucoma medications can augment the surgical success rate.

PMID- 27033965
TI  - The role of computed tomography in the immediate workup of open globe injury.
AB  - PURPOSE: Immediate primary closure is indicated in cases of traumatic open globe
      injury. Orbital computed tomography (CT) is performed prior to primary closure in
      order to rule out possible intraocular foreign bodies (IOFB) and/or damage to
      adjacent extraocular as well as intraocular structures. The aim of the present
      study is to evaluate the yield of orbital CT scan in immediate clinical decision
      making in cases of open globe injury. METHODS: All cases of open globe injury
      treated in our institute during a 10-year period were reviewed. All underwent a
      CT scan before any surgical intervention, regardless of trauma severity. The
      influence of the CT scan results on decisions regarding the immediate treatment
      of the open globe injury was analyzed. RESULTS: A total of 125 cases of open
      globe injury were included in the present study. In none of these cases did the
      CT scan results have any influence on immediate treatment. The CT scan results
      did influence decisions that were made after the immediate operative stage.
      CONCLUSIONS: Computed tomography scan has limited value in immediate clinical
      decision-making in cases of open globe injury scheduled for primary closure.
      While not crucial prior to the initial procedure, it is of value in managing the
      case during the following few days as well as later on. This study suggests that
      a CT scan performed after the initial globe exploration and suturing procedure is
      a valid alternative to stalling the definite globe suturing process until a CT
      scan is obtained and interpreted.

PMID- 27033966
TI  - Epitope mapping and identification of amino acids critical for mouse IgG-binding
      to linear epitopes on Gly m Bd 28K.
AB  - Gly m Bd 28K is one of the major allergens in soybeans, but there is limited
      information on its IgG-binding epitopes. Thirty-four overlapping peptides that
      covered the entire sequence of Gly m Bd 28K were synthesized, and 3 monoclonal
      antibodies against Gly m Bd 28K were utilized to identify the IgG-binding regions
      of Gly m Bd 28K. Three dominant peptides corresponding to
      (28)GDKKSPKSLFLMSNS(42)(G28-S42), (56)LKSHGGRIFYRHMHI(70)(L56-I70), and
      (154)ETFQSFYIGGGANSH(168)(E154-H168) were recognized. L56-I70 is the most
      important epitope, and a competitive ELISA indicated that it could inhibit the
      binding of monoclonal antibody to Gly m Bd 28K protein. Alanine scanning of L56
      I70 documented that F64, Y65, and R66 were the critical amino acids of this
      epitope. Two bioinformatics tools, ABCpred and BepiPred, were used to predict the
      epitopes of Gly m Bd 28K, and the predictions were compared with the epitopes
      that we had located by monoclonal antibodies. 

PMID- 27033967
TI  - Molecular dynamics simulations of uniaxial deformation of thermoplastic
      polyimides.
AB  - The results of atomistic molecular-dynamics simulations of mechanical properties
      of heterocyclic polymer subjected to uniaxial deformation are reported. A new
      amorphous thermoplastic polyimide R-BAPO with a repeat unit consisting of
      dianhydride 1,3-bis-(3',4,-dicarboxyphenoxy)diphenyl (dianhydride R) and diamine
      4,4'-bis-(4''-aminophenoxy)diphenyloxide (diamine BAPO) was chosen for the
      simulations. Our primary goal was to establish the impact of various factors
      (sample preparation method, molecular mass, and cooling and deformation rates) on
      the elasticity modulus. In particular, we found that the elasticity modulus was
      only slightly affected by the degree of equilibration, the molecular mass and the
      size of the simulation box. This is most likely due to the fact that the main
      contribution to the elasticity modulus is from processes on scales smaller than
      the entanglement length. Essentially, our simulations reproduce the logarithmic
      dependence of the elasticity modulus on cooling and deformation rates, which is
      normally observed in experiments. With the use of the temperature dependence
      analysis of the elasticity modulus we determined the flow temperature of R-BAPO
      to be 580 K in line with the experimental data available. Furthermore, we found
      that the application of high external pressure to the polymer sample during
      uniaxial deformation can improve the mechanical properties of the polyimide.
      Overall, the results of our simulations clearly demonstrate that atomistic
      molecular-dynamics simulations represent a powerful and accurate tool for
      studying the mechanical properties of heterocyclic polymers and can therefore be
      useful for the virtual design of new materials, thereby supporting cost-effective
      synthesis and experimental research.

PMID- 27033968
TI  - Rumination and self-control interact to predict bulimic symptomatology in college
      students.
AB  - Recent studies suggest that a ruminative response style may contribute to the
      development and maintenance of Bulimia nervosa. However it is not clear what
      factors may contribute to the relationship between rumination and BN. One factor
      may be self-control, as studies suggest that BN symptomatology relates to
      deficits in self-control. In the present study, we hypothesized that the
      association between rumination and BN symptomatology would be the strongest among
      individuals with lower self-control relative to those with higher self-control.
      Participants were 353 students at a large university. Participants completed
      measures of self-control, rumination, and eating disorder symptomology as part of
      an online study. A hierarchical regression supported an interaction between
      rumination and self-control predicting bulimic symptomatology, controlling for
      BMI. Individuals with higher levels of rumination presented more bulimic symptoms
      if they also had lower levels of self-control, supporting our hypothesis. Based
      on these findings, assessing rumination in conjunction with self-control among
      individuals who present with eating concerns may help to direct treatment.
      Additionally, clinical interventions increasing self-control may also alleviate
      some BN symptoms in ruminators.

PMID- 27033969
TI  - CUB and Sushi multiple domains 3 regulates dendrite development.
AB  - CUB and Sushi multiple domains 3 (CSMD3) is a large protein expressed in fetal
      and adult brain. Recently, mutations of the CSMD3 gene were identified in
      schizophrenia and autism patients. However, biochemical properties and functions
      of the CSMD3 protein remain unknown. Here, we demonstrate that CSMD3 is an
      oligomeric type I transmembrane protein localized in the apical dendrites of
      hippocampal pyramidal neurons in the postnatal brain. In cultured hippocampal
      neurons, CSMD3 is expressed only after 7 days in vitro. Overexpression of CSMD3
      induced dendritic branching in hippocampal neurons. Regulation of dendritic
      morphology by CSMD3 depended on the presence of its extracellular region, while
      CSMD3 intracellular region was dispensable for this activity. These results
      suggest that CSMD3 acts as a co-receptor of an unidentified membrane protein to
      regulate dendrite development. Therefore, malfunctions of CSMD3 may be one of the
      factors in the pathogenesis of psychiatric disorders. 

PMID- 27033970
TI  - Special series: "N=1s".

PMID- 27033971
TI  - Mutagenicity and preclinical safety assessment of the aqueous extract of
      Clinacanthus nutans leaves.
AB  - CONTEXT: Clinacanthus nutans (CN) is used traditionally for treating various
      illnesses. Robust safety data to support its use is lacking. OBJECTIVE: To
      evaluate the adverse effects of aqueous extract of CN leaves (AECNL). MATERIALS
      AND METHODS: The oral toxicity of the AECNL was tested following Organisation for
      Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test)
      of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains.
      RESULTS: No mortality or morbidity was found in the animals upon single and
      repeated dose administration. However, significant body weight loss was observed
      at 2000 mg/kg during sub-chronic (90 d) exposure. In addition, increased
      eosinophil at 500 mg/kg and decreased serum alkaline phosphatase levels at 2000
      mg/kg were observed in male rats. Variations in glucose and lipid profiles in
      treated groups were also observed compared to control. Ames test revealed no
      evidence of mutagenic or carcinogenic effects at 500 MUg/well of AECNL.
      CONCLUSION: The median lethal dose (LD50) of the AECNL is >5000 mg/kg and the no
      observed-adverse-effect level is identified to be greater than 2000 mg/kg/day in
      90-d study.

PMID- 27033972
TI  - Modelling potential photovoltaic absorbers Cu3MCh4(M = V, Nb, Ta; Ch = S, Se, Te)
      using density functional theory.
AB  - The geometric and electronic properties of a series of potential photovoltaic
      materials, the sulvanite structured Cu3MCh4(M = V, Nb, Ta; Ch = S, Se, Te), have
      been computationally examined using both PBEsol+U and HSE06 methods to assess the
      materials' suitability for solar cell application and to compare the predictions
      of the two theoretical approaches. The lattice parameters, electronic density of
      states, and band gaps of the compounds have been calculated to ascertain the
      experimental agreement obtained by each method and to determine if any of the
      systems have an optical band gap appropriate for photovoltaic absorber materials.
      The PBEsol+U results are shown to achieve better agreement with experiment than
      HSE06 in terms of both lattice constants and band gaps, demonstrating that higher
      level theoretical methods do not automatically result in a greater level of
      accuracy than their computationally less expensive counterparts. The PBEsol+U
      calculated optical band gaps of five materials suggest potential suitability as
      photovoltaic absorbers, with values of 1.72 eV, 1.49 eV, 1.19 eV, 1.46 eV, and
      1.69 eV for Cu3VS4, Cu3VSe4, Cu3VTe4, Cu3NbTe4, and Cu3TaTe4, respectively,
      although it should be noted that all fundamental band gaps are indirect in
      nature, which could lower the open-circuit voltage and hence the efficiency of
      prospective devices.

PMID- 27033973
TI  - Phonon-mediated generation of quantum correlations between quantum dot qubits.
AB  - We study the generation of quantum correlations between two excitonic quantum dot
      qubits due to their interaction with the same phonon environment. Such generation
      results from the fact that during the pure dephasing process at finite
      temperatures, each exciton becomes entangled with the phonon environment. We find
      that for a wide range of temperatures quantum correlations are created due to the
      interaction. The temperature-dependence of the level of correlations created
      displays a trade-off type behaviour; for small temperatures the phonon-induced
      distrubance of the qubit states is too small to lead to a distinct change of the
      two-qubit state, hence, the level of created correlations is small, while for
      large temperatures the pure dephasing is not accompanied by the creation of
      entanglement between the qubits and the environment, so the environment cannot
      mediate qubit-qubit quantum correlations. 

PMID- 27033974
TI  - Who decides? The decision-making process of juvenile judges concerning minors
      with mental disorders.
AB  - Previous research on juvenile judges' decision-making process has neglected the
      role of the different actors involved in judicial procedures. The decision can be
      considered as a result of information exchange between the different actors
      involved. The process of making a decision is equally important as the decision
      itself, especially when the decision considers minors with mental disorders. The
      presence and the type of interaction determine the information available to the
      juvenile judges to make their final decision. The overall aim of this study is to
      gain insight into the role of all actors, including the juvenile judge, in the
      juvenile judge's decision-making process in cases relating to minors with mental
      disorders. Semi-structured interviews were carried out with professional actors
      (n=32), minors (n=31) and parents (n=17). The findings indicated that the judge's
      decision is overall the result of an interaction between the juvenile judge, the
      social services investigator and the youth psychiatrist. The other professional
      actors, the minors and the parents had only a limited role in the decision-making
      process. The research concludes that the judge's decision-making process should
      be based on dialogue, and requires enhanced collaboration between the juvenile
      court and youth psychiatrists from mental health services. Future decision-making
      research should pay more attention to the interactions of the actors that guide a
      juvenile judge's decision.

PMID- 27033975
TI  - Exploring and explaining involuntary care: The relationship between psychiatric
      admission status, gender and other demographic and clinical variables.
AB  - Involuntary admission and treatment are features of psychiatric care in many
      countries, but the relationship between involuntary status and gender (among
      other factors) is not clear. We examined demographic and diagnostic factors
      associated with involuntary admission in a general adult psychiatry service in a
      deprived area of Dublin's north inner-city over a 7-year period (2008 to 2014
      inclusive). Over this period, there were 1099 admissions, yielding an annual
      admission rate of 504.8 admissions per 100,000 population per year. When adjusted
      for deprivation, this rate (387.7) was lower than the national rate (413.9).
      Consistent with other inner-city areas in Dublin, 14.1% of admissions were
      involuntary, yielding an involuntary admission rate of 71.2 per 100,000
      population per year (deprivation-adjusted rate: 54.8), which is higher than the
      national rate (39.4). After controlling for age, occupation, marital status and
      diagnosis, the only independent predictors of admission status were place of
      origin (p<0.001) and male gender (p=0.001). These findings are consistent with
      studies showing associations between male gender and involuntary status in the
      United States, New Zealand, Netherlands, Norway, Belgium, France, and Luxembourg.
      In contrast, female gender is associated with involuntary status in Switzerland,
      Brazil, and China. These cross-national differences are likely related to
      differing legal traditions and different criteria for involuntary admission,
      possibly related to varying emphases placed on "dangerousness" as a mandatory
      criterion for involuntary hospitalization. This merits further, cross-national
      study.

PMID- 27033976
TI  - An alternative strategy for targeted gene replacement in plants using a dual
      sgRNA/Cas9 design.
AB  - Precision DNA/gene replacement is a promising genome-editing tool that is highly
      desirable for molecular engineering and breeding by design. Although the
      CRISPR/Cas9 system works well as a tool for gene knockout in plants, gene
      replacement has rarely been reported. Towards this end, we first designed a
      combinatory dual-sgRNA/Cas9 vector (construct #1) that successfully deleted miRNA
      gene regions (MIR169a and MIR827a). The deletions were confirmed by PCR and
      subsequent sequencing, yielding deletion efficiencies of 20% and 24% on MIR169a
      and MIR827a loci, respectively. We designed a second structure (construct #2)
      that contains sites homologous to Arabidopsis TERMINAL FLOWER 1 (TFL1) for
      homology-directed repair (HDR) with regions corresponding to the two sgRNAs on
      the modified construct #1. The two constructs were co-transformed into
      Arabidopsis plants to provide both targeted deletion and donor repair for
      targeted gene replacement by HDR. Four of 500 stably transformed T0 transgenic
      plants (0.8%) contained replaced fragments. The presence of the expected
      recombination sites was further confirmed by sequencing. Therefore, we
      successfully established a gene deletion/replacement system in stably transformed
      plants that can potentially be utilized to introduce genes of interest for
      targeted crop improvement. 

PMID- 27033977
TI  - Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone
      development.
AB  - How lineage specifiers are regulated during development is an outstanding
      question, and the molecular regulation of osteogenic factor RUNX2 remains to be
      fully understood. Here we report that the Mediator subunit MED23 cooperates with
      RUNX2 to regulate osteoblast differentiation and bone development. Med23 deletion
      in mesenchymal stem cells or osteoblast precursors results in multiple bone
      defects similar to those observed in Runx2(+/-) mice. In vitro, Med23-deficient
      progenitor cells are refractory to osteoblast differentiation, and Med23
      deficiency reduces Runx2-target gene activity without changing Runx2 expression.
      Mechanistically, MED23 binds to RUNX2 and modulates its transcriptional activity.
      Moreover, Med23 deficiency in osteoprogenitor cells exacerbates the skeletal
      abnormalities observed in Runx2(+/-) mice. Collectively, our results establish a
      genetic and physical interaction between RUNX2 and MED23, suggesting that MED23
      constitutes a molecular node in the regulatory network of anabolic bone formation
      and related diseases. 

PMID- 27033978
TI  - Association of disclosure of HIV status with medication adherence.
AB  - OBJECTIVE: Disclosure may affect adherence to antiretroviral treatment. In a
      medication adherence program, this cross-sectional study describes disclosure,
      perceived reaction after disclosure, living situations, and the relationship of
      disclosure with antiretroviral adherence. METHODS: A combination of a
      questionnaire to measure disclosure and longitudinal electronic monitoring of
      medication adherence was used. RESULTS: A total of 103 out of 159 eligible
      patients gave informed consent. The characteristics differed between participants
      and nonparticipants (race, education, sexual orientation, medication adherence).
      Thirteen participants did not disclose their HIV status. Seventy-three (81%)
      participants judged the reaction after disclosure positive. Among the 62
      participants cohabiting, 52% disclosed to all co-residents. Adherence was high
      (median 100%). HIV disclosure was negatively associated with adherence, when
      disclosing to the mother (OR=2.46, p-value=0.086) and to siblings (OR=2.89, p
      value=0.029). Living alone was associated to a lower adherence than cohabitation
      (Rate Ratio=1.42, p-value=0.007). CONCLUSION: HIV disclosure and adherence are
      sensitive issues, which may explain the reason for refusal. Nonparticipants may
      be those with the most difficulties disclosing. PRACTICE IMPLICATIONS: An
      unbiased collection of sensitive information, as HIV disclosure, is a difficult
      task. A cohort design, with research data collected systematically by a trusted
      healthcare provider, may better describe the association between adherence and
      disclosure.

PMID- 27033979
TI  - Enhanced immune response to MMP3 stimulation in microglia expressing mutant
      huntingtin.
AB  - Huntington's Disease (HD) is an inherited neurodegenerative disease caused by a
      polyglutamine expansion in the huntingtin protein. The YAC128 mouse model of HD
      expresses the full-length human huntingtin protein with 128 CAG repeats and
      replicates the phenotype and neurodegeneration that occur in HD. Several studies
      have implicated a role for neuroinflammation in HD pathogenesis. Studies on
      presymptomatic HD patients have illustrated microgliosis (activated microglia) in
      brain regions affected in HD. Mutant huntingtin expressing isolated primary
      monocytes (human HD patients) and primary macrophages (YAC128) are overactive in
      response to lipopolysaccharide (LPS) stimulation. In this study we demonstrate
      that cultured primary microglia (the resident immune cells of the brain cells)
      from YAC128 mice differentially express a wide number of cytokines compared to
      wildtype microglia cultures in response to LPS. Furthermore, this study outlines
      a direct interaction between mutant huntingtin and cytokine secretion in HD
      microglia. Increased cytokine release in YAC128 microglia can be blocked by
      cannabinoid activation or by mutant huntingtin knockdown with anti-sense
      oligonucleotide treatment. Matrix metalloprotease 3 (MMP3), an endogenous
      neuronal activator of microglia, also induces increased cytokine release from
      YAC128 microglia compared to wildtype microglia. We found elevated MMP levels in
      HD CSF, and MMP levels correlate with disease severity in HD. These data support
      a novel role for MMPs and microglial activation in HD pathogenesis. With an
      improved understanding of the specific cellular processes involved in HD
      neuroinflammation, novel therapeutic agents targeting these processes can be
      developed and hold great promise in the treatment of HD.

PMID- 27033980
TI  - Electromembrane surrounded solid phase microextraction using electrochemically
      synthesized nanostructured polypyrrole fiber.
AB  - Electromembrane surrounded solid phase microextraction using conductive polymers
      as the sorbent is carried out for the first time for extraction of two
      antidepressants including amitriptyline (AMI) and doxepin (DOX), as model
      analytes. The polypyrrole coating was prepared and utilized as both cathode and
      SPME sorbent. Different variables such as the conditions for preparation of
      polypyrrole fiber, pH of the donor and the acceptor phases, applied voltage, and
      extraction time were optimized. Under the optimized conditions, figures of merit
      of the proposed method were investigated in human whole blood and urine samples.
      Intra- and inter-assay precisions ranged between 3.1-7.5% and 7.6-12.3%,
      respectively were obtained in different extraction media. Detection limits of
      0.15 and 0.05 for AMI and 0.3 and 0.1 ng mL(-1) for DOX were achieved in the
      urine and blood samples, respectively. Linearity of the method was studied up to
      50.0 ng mL(-1) for both analytes and coefficients of determination better than
      0.9966 were achieved. Regardless of the high sample cleanup, which makes the
      proposed method suitable for analysis of drugs from complicated matrices, clean
      chromatograms were obtained. Finally, the proposed method was applied for
      analysis of AMI and DOX in different real samples and reasonable data were
      obtained.

PMID- 27033981
TI  - Fast environment-friendly ball mill-assisted deep eutectic solvent-based
      extraction of natural products.
AB  - A fast environment-friendly extraction method, ball mill-assisted deep eutectic
      solvent-based extraction, was used for the extraction of natural products from
      plants. In this study, tanshinones were selected as target compounds to evaluate
      the efficiency of the developed extraction method. Under the optimized
      experimental conditions, cryptotanshinone (0.176 mg/g), tanshinone I (0.181
      mg/g), and tanshinone II A (0.421 mg/g) were extracted from Salvia miltiorrhiza
      Bunge, and the developed method was found to be greener, more efficient, and
      faster than conventional, environmentally harmful extraction methods such as
      methanol-based ultrasound-assisted extraction and heat reflux extraction. The
      analytical performances including recovery, reproducibility (RSD, n=5),
      correlation of determination (r(2)), and the limit of detection, with the ranges
      of 96.1-103.9%, 1.6-1.9%, 0.9973-0.9984, and 5-8 ng/mL, were respectively
      obtained. Application of ball mill-assisted deep eutectic solvent-based
      extraction may fundamentally shape the future development of extraction methods.

PMID- 27033982
TI  - A simple method for the synthesis of a polar-embedded and polar-endcapped
      reversed-phase chromatographic packing with low activity of residue silanols.
AB  - Octadecyl bonded silica (ODS) is the most popular packing for reversed-phase
      chromatography. However, it generally demonstrates bad resolution for polar
      analytes because of the residue silanols and its poor stability in aqueous mobile
      phase. To address the problem, a new reversed-phase packing containing both polar
      embedded and polar-endcapped moieties was proposed. It was prepared by a very
      simple method, in which the epoxide addition reaction of 3
      glycidoxypropyltrimethoxysilane with 1-octadecanethiol proceeded simultaneously
      with the reaction of silane coupling onto silica particles. By controlling the
      molecular ratio of 3-glycidoxypropyltrimethoxysilane to 1-octadecanethiol higher
      than 1.0 (1.56 for the present study), both polar-embedded and polar-endcapped
      moieties were achieved onto the packing. The performance of the packing was
      evaluated in detail. The results demonstrated that neutral, acidic and basic
      analytes were well separated on the packing. The column efficiency for
      phenanthrene was 34,200 theoretical plates per meter. In addition, four
      nucleotides can be separated in 100% phosphate buffered saline solution with good
      reproducibility, which indicates the packing has good stability in aqueous mobile
      phase. Amitriptyline, a typical basic analytes, was eluted out with relatively
      symmetric peak shape (asymmetry factor of 1.36), which implies that the packing
      has not suffered from the negative effect of residue silanols significantly. Good
      stability in buffer solution of pH ranging from 2.0 to 10.0 was also documented
      for the packing. 

PMID- 27033983
TI  - Ferrite nanospheres-based magnetic solid-phase extraction for determination of
      domoic acid in seawater samples using high-performance liquid chromatography with
      tandem mass spectrometry.
AB  - A simple, rapid and sensitive method for determination of trace levels of domoic
      acid (DA) in seawater was developed, based on a magnetic solid-phase extraction
      (MSPE) followed by high-performance liquid chromatography with tandem mass
      spectrometry (HPLC-MS/MS). Five kinds of ferrite magnetic nanospheres (MFe2O4;
      M=Fe, Co, Ni, Cu and Zn) were prepared and first used as sorbents for MSPE of DA
      and removal of salt interference. Under the same extraction and elution
      conditions, CuFe2O4 magnetic nanospheres provided the best pretreatment
      performance, which were then characterized in detail. After further optimization
      of conditions, the developed method showed good linearity (r(2)=0.9991) with the
      range of 5-1000 pg mL(-1), low limit of detection (2.5 pg mL(-1); S/N=3:1), low
      limit of quantification (5.0 pg mL(-1); S/N=10:1), and good recoveries (86.0
      98.1%) with acceptable repeatability (RSD <= 6.5%; n=3) in seawater samples. The
      results demonstrated that the ferrite magnetic nanospheres are promising sorbents
      for efficient extraction of highly polar analytes from high ionic strength
      solutions.

PMID- 27033984
TI  - Poly(o-anisidine)/graphene oxide nanosheets composite as a coating for the
      headspace solid-phase microextraction of benzene, toluene, ethylbenzene and
      xylenes.
AB  - A poly(o-anisidine)/graphene oxide nanosheets (PoA/GONSs) coating is fabricated
      by a simple and efficient electrochemical deposition method on steel wire. The
      incorporation of PoA and GONSs allows preparing a nanocomposite that can
      successfully integrate the advantages of both. Then, the prepared fiber is
      applied to the headspace solid-phase microextraction (HS-SPME) and gas
      chromatographic analysis of benzene, toluene, ethylbenzene and xylenes. In order
      to obtain an adherent, stable and efficient fiber to extract target analytes,
      experimental parameters related to the coating process such as deposition
      potential, deposition time, concentration of the monomer and concentration of
      GONSs were studied. The prepared composite fiber were characterized by Fourier
      transform infrared spectroscopy, powder X-ray diffraction and scanning electron
      microscopy. The effect of various parameters on the efficiency of HS-SPME process
      consisting of desorption temperature and time, extraction temperature and time
      and ionic strength were also optimized. Under the optimal conditions, the method
      was linear for orders of magnitude with correlation coefficients varying from
      0.9888 to 0.9993. Intra- and inter-day precisions of the method were determined
      from mixed aqueous solutions containing 5.0 ng mL(-1) of each BTEX. The intra-day
      precisions varied from 3.1% for toluene to 5.7% for ethylbenzene, while the inter
      day precisions varied from 4.9% for o-xylene to 7.3% for m,p-xylene. Limits of
      detection were in the range 0.01-0.06 ng mL(-1). The proposed method was applied
      to monitor BTEX compounds in some water samples and the accuracies found through
      spiking river water samples showed high recoveries between 92.0 and 101.2%.

PMID- 27033985
TI  - The best papers of Georges Guiochon.

PMID- 27033986
TI  - Rapid determination of moisture content in paper materials by multiple headspace
      extraction gas chromatography.
AB  - This paper describes a new method for the rapid determination of the moisture
      content in paper materials. The method is based on multiple headspace extraction
      gas chromatography (MHE-GC) at a temperature above the boiling point of water,
      from which an integrated water loss from the tested sample due to evaporation can
      be measured and from which the moisture content in the sample can be determined.
      The results show that the new method has a good precision (with the relative
      standard deviation <0.96%), high sensitivity (the limit of quantitation=0.005%)
      and good accuracy (the relative differences <1.4%). Therefore, the method is
      quite suitable for many uses in research and industrial applications. 

PMID- 27033987
TI  - The coupling between spatial attention and other components of task-set: A task
      switching investigation.
AB  - Is spatial attention reconfigured independently of, or in tandem with, other task
      set components when the task changes? We tracked the eyes of participants cued to
      perform one of three digit-classification tasks, each consistently associated
      with a distinct location. Previously we observed, on task switch trials, a
      substantial delay in orientation to the task-relevant location and tendency to
      fixate the location of the previously relevant task-"attentional inertia". In the
      present experiments the cues specified (and instructions emphasized) the relevant
      location rather than the current task. In Experiment 1, with explicit spatial
      cues (arrows or spatial adverbs), the previously documented attentional handicaps
      all but disappeared, whilst the performance "switch cost" increased. Hence,
      attention can become decoupled from other aspects of task-set, but at a cost to
      the efficacy of task-set preparation. Experiment 2 used arbitrary single-letter
      cues with instructions and a training regime that encouraged participants to
      interpret the cue as indicating the relevant location rather than task. As in our
      previous experiments, and unlike in Experiment 1, we now observed clear switch
      induced attentional delay and inertia, suggesting that the natural tendency is
      for spatial attention and task-set to be coupled and that only quasi-exogenous
      location cues decouple their reconfiguration. 

PMID- 27033988
TI  - Understanding the natural history and clinical implications of airways infections
      in CF - Moving beyond the classics.

PMID- 27033989
TI  - End of life critical patients: A multicenter study in Spanish Intensive Care
      Units.

PMID- 27033990
TI  - Finding Your WayTM: a collaborative approach to increase awareness of missing
      person events among persons with dementia.
AB  - AIM: To describe an innovative community-wide program aimed at increasing
      awareness of risks of missing person events among persons with dementia targeting
      various cultural groups and to present preliminary evaluation findings. METHODS:
      Review of program records to describe program implementation and a community
      partner survey. RESULTS: Over 23 months, 386 partnerships were established to
      implement the program; 941 awareness-raising sessions were conducted reaching
      23,495 individuals. There is an upward trend in number of sessions conducted in
      various languages and attendance. Community partners' (>85%) responded positively
      to the program and consultation process. CONCLUSION: This partnership experience
      demonstrates the effectiveness of a collaborative approach to the development and
      widespread dissemination of information and resource materials aimed at ensuring
      the safety of a vulnerable population.

PMID- 27033991
TI  - Direct green waste land application: How to reduce its impacts on greenhouse gas
      and volatile organic compound emissions?
AB  - Direct land application as an alternative to green waste (GW) disposal in
      landfills or composting requires an understanding of its impacts on greenhouse
      gas (GHG) and volatile organic compound (VOC) emissions. We investigated the
      effects of two approaches of GW direct land application, surface application and
      soil incorporation, on carbon dioxide (CO2), nitrous oxide (N2O) and methane
      (CH4), and VOC emissions for a 12month period. Five treatments were applied in
      fall 2013 on fallow land under a Mediterranean climate in California: 30cm height
      GW on surface; 15cm height GW on surface; 15cm height GW tilled into soil;
      control+till; control+no till. In addition, a laboratory experiment was conducted
      to develop a mechanistic understanding of the influence of GW application on soil
      O2 consumption and GHG emission. The annual cumulative N2O, CO2 and VOC emissions
      ranged from 1.6 to 5.5kgN2O-Nha(-1), 5.3 to 40.6MgCO2-Cha(-1) and 0.6 to
      9.9kgVOCha(-1), respectively, and were greatly reduced by GW soil incorporation
      compared to surface application. Application of GW quickly consumed soil O2
      within one day in the lab incubation. These results indicate that to reduce GHG
      and VOC emissions of GW direct land application, GW incorporation into soil is
      recommended. 

PMID- 27033992
TI  - Potential reuse of small household waste electrical and electronic equipment:
      Methodology and case study.
AB  - This study proposes a general methodology for assessing and estimating the
      potential reuse of small waste electrical and electronic equipment (sWEEE),
      focusing on devices classified as domestic appliances. Specific tests for visual
      inspection, function and safety have been defined for ten different types of
      household appliances (vacuum cleaner, iron, microwave, toaster, sandwich maker,
      hand blender, juicer, boiler, heater and hair dryer). After applying the tests,
      reuse protocols have been defined in the form of easy-to-apply checklists for
      each of the ten types of appliance evaluated. This methodology could be useful
      for reuse enterprises, since there is a lack of specific protocols, adapted to
      each type of appliance, to test its potential of reuse. After applying the
      methodology, electrical and electronic appliances (used or waste) can be
      segregated into three categories: the appliance works properly and can be
      classified as direct reuse (items can be used by a second consumer without prior
      repair operations), the appliance requires a later evaluation of its potential
      refurbishment and repair (restoration of products to working order, although with
      possible loss of quality) or the appliance needs to be finally discarded from the
      reuse process and goes directly to a recycling process. Results after applying
      the methodology to a sample of 87.7kg (96 units) show that 30.2% of the
      appliances have no potential for reuse and should be diverted for recycling,
      while 67.7% require a subsequent evaluation of their potential refurbishment and
      repair, and only 2.1% of them could be directly reused with minor cleaning
      operations. This study represents a first approach to the "preparation for reuse"
      strategy that the European Directive related to Waste Electrical and Electronic
      Equipment encourages to be applied. However, more research needs to be done as an
      extension of this study, mainly related to the identification of the feasibility
      of repair or refurbishment operations. 

PMID- 27033993
TI  - Valorisation of ferric sewage sludge ashes: Potential as a phosphorus source.
AB  - Sewage sludge ashes (SSA), although a waste, contain elements with socio-economic
      and environmental potential that can be recovered. This is the case of phosphorus
      (P). SSA from two Danish incinerators were collected during two years and
      characterized. The sampling was done immediately after incineration (fresh SSA)
      or from an outdoor deposit (deposited SSA). Although morphology and mineral
      composition were similar, physico-chemical and metal concentration differences
      were found between incinerator plants and sampling periods. No differences were
      observed between deposited and fresh SSA, except for the parameters directly
      influenced by disposal conditions (e.g. moisture content). All the SSAs had high
      concentrations of P (up to 16wt%), but they all exceeded Danish EPA Cd and Ni
      thresholds for direct application at agricultural soil. Fresh and deposited SSA
      were acid washed aiming P extraction, achieving 50gP/kg (approx. 37% of total P),
      but metals were also co-extracted to the liquid phase. To avoid and/or minimize
      the metals pollution of the extracted P, selective P recovery from the SSA was
      tested, using the electrodialytic (ED) process. ED laboratory cells, with 3
      compartments (3c) and 2 compartments (2c), and two acid concentrations (H2SO4,
      0.08M and 0.19M) were used for 7days. The most concentrated acid solution
      increased P solubilization. The 2c-cell combined with the higher acid
      concentration resulted in higher P recoveries, 125g of P/kg of SSA in the
      anolyte. The obtained results showed that the ED process is a valuable tool for
      the SSA valorisation as it promotes simultaneous P recovery and metals extraction
      from the SSA. 

PMID- 27033994
TI  - An easy-to-use tool for the evaluation of leachate production at landfill sites.
AB  - A simulation program for the evaluation of leachate generation at landfill sites
      is herein presented. The developed tool is based on a water balance model that
      accounts for all the key processes influencing leachate generation through
      analytical and empirical equations. After a short description of the tool,
      different simulations on four Italian landfill sites are shown. The obtained
      results revealed that when literature values were assumed for the unknown input
      parameters, the model provided a rough estimation of the leachate production
      measured in the field. In this case, indeed, the deviations between observed and
      predicted data appeared, in some cases, significant. Conversely, by performing a
      preliminary calibration for some of the unknown input parameters (e.g. initial
      moisture content of wastes, compression index), in nearly all cases the model
      performances significantly improved. These results although showed the potential
      capability of a water balance model to estimate the leachate production at
      landfill sites also highlighted the intrinsic limitation of a deterministic
      approach to accurately forecast the leachate production over time. Indeed,
      parameters such as the initial water content of incoming waste and the
      compression index, that have a great influence on the leachate production, may
      exhibit temporal variation due to seasonal changing of weather conditions (e.g.
      rainfall, air humidity) as well as to seasonal variability in the amount and type
      of specific waste fractions produced (e.g. yard waste, food, plastics) that make
      their prediction quite complicated. In this sense, we believe that a tool such as
      the one proposed in this work that requires a limited number of unknown
      parameters, can be easier handled to quantify the uncertainties. 

PMID- 27033995
TI  - A novel method for material characterization of reusable products.
AB  - Product reuse contributes favorably to waste management and resource recovery by
      diverting products from terminal disposal to second-hand urban markets. Many
      organizations with social mission incorporate in their activities the process of
      reuse, thus making valuable products available to second-hand customers through
      their thrift stores. Data management and product classification are an important
      aspect of quantitative analysis of second-hand products circulating through reuse
      organizations. The New York City Center for Materials Reuse has, for the last
      10years, organized the reuse activities of most not for profit organizations, and
      collected valuable information on the strengths and weaknesses of their
      operations. One such finding is the casual, and inconsistent approach used by
      these organizations to keep a record of the level and value of the reuse efforts
      they undertake. This paper describes a novel methodology developed to standardize
      record keeping and characterize commonly reused post-consumer products by
      assessing the outgoing product flow from reuse organizations. The approach groups
      material composition of individual products into main product categories,
      creating a simplified method to characterize products. Furthermore, by linking
      product categories and material composition, the method creates a matrix to help
      identify the material composition of products handled by reuse organizations. As
      part of the methodology, whenever adequate data are not available about certain
      types of products, a process identified as "field characterization study" is
      proposed and incorporated in the implementation to develop meaningful and useful
      data on the weight and material composition. Finally, the method incorporates the
      estimation of the environmental impact of reuse using standard models available
      through the U.S. Environmental Protection Agency and other worldwide entities.
      The diversified weight and size of products poses a challenge to the statistical
      significance of the estimated weights. A case study is presented, illustrating
      how the proposed methodology can be applied to estimate environmental benefits
      from the sale of second-hand products in reuse organizations. 

PMID- 27033996
TI  - [Chronic spontaneous diploic haematoma].

PMID- 27033997
TI  - [Neuromonitoring in severe paediatric head injury].

PMID- 27033998
TI  - Birth mode-dependent association between pre-pregnancy maternal weight status and
      the neonatal intestinal microbiome.
AB  - The intestinal microbiome is a unique ecosystem that influences metabolism in
      humans. Experimental evidence indicates that intestinal microbiota can transfer
      an obese phenotype from humans to mice. Since mothers transmit intestinal
      microbiota to their offspring during labor, we hypothesized that among vaginal
      deliveries, maternal body mass index is associated with neonatal gut microbiota
      composition. We report the association of maternal pre-pregnancy body mass index
      on stool microbiota from 74 neonates, 18 born vaginally (5 to overweight or obese
      mothers) and 56 by elective C-section (26 to overweight or obese mothers).
      Compared to neonates delivered vaginally to normal weight mothers, neonates born
      to overweight or obese mothers had a distinct gut microbiota community structure
      (weighted UniFrac distance PERMANOVA, p < 0.001), enriched in Bacteroides and
      depleted in Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus. We
      show that these microbial signatures are predicted to result in functional
      differences in metabolic signaling and energy regulation. In contrast, among
      elective Cesarean deliveries, maternal body mass index was not associated with
      neonatal gut microbiota community structure (weighted UniFrac distance PERMANOVA,
      p = 0.628). Our findings indicate that excess maternal pre-pregnancy weight is
      associated with differences in neonatal acquisition of microbiota during vaginal
      delivery, but not Cesarean delivery. These differences may translate to altered
      maintenance of metabolic health in the offspring. 

PMID- 27033999
TI  - Polymeric microcontainers improve oral bioavailability of furosemide.
AB  - Microcontainers with an inner diameter of 223 MUm are fabricated using the
      polymer SU-8, and evaluated in vitro, in situ and in vivo for their application
      as an advanced oral drug delivery system for the poorly water soluble drug
      furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the
      microcontainers followed by applying a lid using Eudragit L100. It is possible to
      control the drug release in vitro, and in vitro absorption studies show that the
      microcontainers are not a hindrance for absorption of ASSF. In situ perfusion
      studies in rats are performed with ASSF-filled microcontainers coated with
      Eudragit and compared to a furosemide solution. The absorption rate constant of
      ASSF confined in microcontainers is found to be significantly different from the
      solution, and by light microscopy, it is observed that the microcontainers are
      engulfed by the intestinal mucus. An oral bioavailability study in rats is
      performed with ASSF confined in microcontainers coated with Eudragit and a
      control group with ASSF in Eudragit-coated capsules. A relative bioavailability
      of 220% for the ASSF in microcontainers compared to ASSF in capsules is found.
      These studies indicate that the microcontainers could serve as a promising oral
      drug delivery system.

PMID- 27034000
TI  - Formulation of insulin-loaded N-trimethyl chitosan microparticles with improved
      efficacy for inhalation by supercritical fluid assisted atomization.
AB  - Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation
      mixer (SAA-HCM) was proposed as a green technique to fabricate insulin-loaded dry
      powders for inhalation administration. N-trimethyl chitosan (TMC), a polymeric
      mucoadhesive absorption enhancer, was synthesized and successfully micronized
      from aqueous solution using SAA-HCM. The prepared well-defined spherical TMC
      microparticles with preserved structure and thermal stability were potential
      carriers for delivery of proteins. Then, insulin-loaded TMC microparticles with
      high loading efficiency were coprecipitated from aqueous solutions using SAA-HCM
      without use of any organic solvents. The polymer/protein ratio revealed to be a
      factor influencing the particle morphology, and non-coalescing composite
      microparticles in amorphous state mainly ranging from 1MUm to 5MUm could be
      obtained in this work. Aerodynamic properties were assessed by next generation
      impactor (NGI) and the mass median aerodynamic diameter (MMAD) lied inside the
      inhalable range of 1-5MUm, while fine particle fraction (FPF) reached above 60%.
      The structural integrity of encapsulated insulin was confirmed by HPLC, circular
      dichroism and fluorescence spectroscopy. In vivo study demonstrated that TMC
      could enhance the absorption and bioavailability of the pulmonarily administered
      insulin formulation for SD rats. These results suggest that TMC microparticles
      could be efficiently prepared as a promising vehicle for drug delivery, and SAA
      HCM is a promising technique to prepare inhalable polymer/protein composite dry
      powders. 

PMID- 27034001
TI  - Drug permeation and cellular interaction of amino acid-coated drug combination
      powders for pulmonary delivery.
AB  - The effect of three amino acid coatings (L-leucine, L-valine and L-phenylalanine)
      on particle integrity, aerosolization properties, cellular interaction,
      cytocompatibility, and drug permeation properties of drug combination powder
      particles (beclomethasone dipropionate and salbutamol sulphate) for dry powder
      inhalation (DPI) was investigated. Particles with crystalline L-leucine coating
      resulted in intact separated particles, with crystalline L-valine coating in
      slightly sintered particles and with amorphous L-phenylalanine coating in
      strongly fused particles. The permeation of beclomethasone dipropionate across a
      Calu-3 differentiated cell monolayer was increased when compared with its
      physical mixture. Drug crystal formation was also observed on the Calu-3 cell
      monolayer. The L-leucine coated particles were further investigated for
      cytocompatibility in three human pulmonary (Calu-3, A549 and BEAS-2B) and one
      human macrophage (THP-1) cell lines, where they showed excellent tolerability.
      The l-leucine coated particles were also examined for their ability to elicit
      reactive oxygen species in pulmonary BEAS-2B and macrophage THP-1 cell lines. The
      study showed the influence of the amino acid coatings for particle formation and
      performance and their feasibility for combination therapy for pulmonary delivery.

PMID- 27034002
TI  - Novel nanoemulsion based lipid nanosystems for favorable in vitro and in vivo
      characteristics of curcumin.
AB  - The goal of this study was to assess the enhanced elementary characteristics, in
      vitro release, anti-cancer cytotoxicity, in situ absorption and in vivo
      bioavailability of a novel nanoemulsion based lipid nanosystems containing
      curcumin (CNELNs) when administered orally. The CNELNs were first fabricated by
      loading water-in-oil nanoemulsions into lipid nanosystems using a nanoemulsion
      film dispersion-sonication method. The gastro-intestinal absorption, in vitro
      release and in vivo kinetic property of CNELNs were investigated using an in situ
      perfusion method, a dialysis method and a concentration-time curve based method,
      respectively. The inhibitory effects of CNELNs on human lung cancer A549 cell
      growth were determined using MTT assay. The absorption constants and effective
      permeabilities of CNELNs in different gastro-intestinal tracts increased 2.29
      4.04 times and 4.06-8.27 times that of curcumin (CUR), respectively. The relative
      bioavailability of CNELNs to free CUR was 733.59%. CNELNs inhibited A549 growth
      in a dose- and time-dependent manner. CNELNs markedly improved the oral
      bioavailability of CUR which was probably due to the increased gastro-intestinal
      absorption. CNELNs had stronger inhibitory effects on the viabilities of A549
      cells than that of free CUR. CNELNs might be promising nanosystems for oral
      delivery of CUR to satisfy clinical requirements. 

PMID- 27034003
TI  - Preparation, characterization and in vivo evaluation of amorphous tacrolimus
      nanosuspensions produced using CO2-assisted in situ nanoamorphization method.
AB  - Unlike conventional 'top-down' and 'bottom-up' techniques, a novel low-cost CO2
      assisted in situ nanoamorphization (ISN) method has been developed to prepare
      amorphous drug nanosuspensions. In order to improve the dissolution rate and oral
      bioavailability of tacrolimus (FK506), herein FK506 nanosuspensions with
      different particle size were successfully prepared using ISN method through
      adjusting the amount of acid-base pair and the stabilizer, the mean particle
      sizes of obtained FK506 nanosuspensions were 167.3+/-2.8nm (FK506-NA), 302.8+/
      2.0nm (FK506-NB) and 513.5+/-15.1nm (FK506-NC), respectively. Differential
      scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) confirmed the
      amorphous state of FK506 in all nanosuspensions that would be beneficial to the
      improvement of drug bioavailability because the amorphous drug form is more
      soluble and has a higher dissolution rate than the crystalline state. In vitro
      dissolution studies showed that the dissolution rate order of different
      formulation is as follows: FK506-NB>FK506-NA>FK506-NC>FK506-D (without acid-base
      pair included)>Prograf((r)) (commercial hard capsule). In vivo pharmacokinetic
      studies showed that all FK506 nanosuspensions clearly increased the oral
      bioavailability of FK506 in comparison with Prograf((r)), especially for FK506
      NB. The Cmax and AUC0-12h of FK506-NB were about 2.05-fold (p<0.01) and 1.5-fold
      (p<0.05) higher than that of Prograf((r)). These findings suggest that this
      simple and versatile ISN technique has great potential for use in the preparation
      of nanosuspensions to increase drug oral bioavailability. 

PMID- 27034004
TI  - Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer.
AB  - Therapeutic resistance to trastuzumab caused by dysregulation of long noncoding
      RNAs (lncRNAs) is a major obstacle to clinical management of HER2-positive breast
      cancer. To investigate which lncRNAs contribute to trastuzumab resistance, we
      screened a microarray of lncRNAs involved in the malignant phenotype of
      trastuzumab-resistant SKBR-3/Tr cells. Expression of the lncRNA GAS5 was
      decreased in SKBR-3/Tr cells and in breast cancer tissue from trastuzumab-treated
      patients. Inhibition of GAS5 promoted SKBR-3 cell proliferation, and GAS5
      knockdown partially reversed lapatinib-induced inhibition of SKBR-3/Tr cell
      proliferation. GAS5 suppresses cancer proliferation by acting as a molecular
      sponge for miR-21, leading to the de-repression of phosphatase and tensin
      homologs (PTEN), the endogenous target of miR-21. Moreover, mTOR activation
      associated with reduced GAS5 expression was required to suppress PTEN. This work
      identifies GAS5 as a novel prognostic marker and candidate drug target for HER2
      positive breast cancer. 

PMID- 27034005
TI  - Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory
      principles.
AB  - B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK
      pathway and a pharmacological target of growing clinical relevance, in particular
      in oncology. To understand how B-Raf itself is regulated, we combined mass
      spectrometry with genetic approaches to map its interactome in MCF-10A cells as
      well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1
      double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf
      expression vectors. Using a multi-protease digestion approach, we identified a
      novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly,
      we identify two evolutionary conserved phosphorylation clusters around T401 and
      S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up
      revealed that these clusters are phosphorylated in the contexts of oncogenic Ras,
      sorafenib induced Raf dimerization and in the background of the V600E mutation.
      We further show that the vemurafenib sensitive phosphorylation of the T401
      cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues
      of this cluster by alanine residues enhances the transforming potential of B-Raf,
      indicating that these phosphorylation sites suppress its signaling output.
      Moreover, several B-Raf phosphorylation sites, including T401 and S419, are
      somatically mutated in tumors, further illustrating the importance of
      phosphorylation for the regulation of this kinase. 

PMID- 27034006
TI  - Human papillomavirus oncogenic E6 protein regulates human beta-defensin 3 (hBD3)
      expression via the tumor suppressor protein p53.
AB  - Human beta-defensin-3 (hBD3) is an epithelial cell-derived innate immune
      regulatory molecule overexpressed in oral dysplastic lesions and fosters a tumor
      promoting microenvironment. Expression of hBD3 is induced by the epidermal growth
      factor receptor signaling pathway. Here we describe a novel pathway through which
      the high-risk human papillomavirus type-16 (HPV-16) oncoprotein E6 induces hBD3
      expression in mucosal keratinocytes. Ablation of E6 by siRNA induces the tumor
      suppressor p53 and diminishes hBD3 in HPV-16 positive CaSki cervical cancer cells
      and UM-SCC-104 head and neck cancer cells. Malignant cells in HPV-16-associated
      oropharyngeal cancer overexpress hBD3. HPV-16 E6 induces hBD3 mRNA expression,
      peptide production and gene promoter activity in mucosal keratinocytes. Reduction
      of cellular levels of p53 stimulates hBD3 expression, while activation of p53 by
      doxorubicin inhibits its expression in primary oral keratinocytes and CaSki
      cells, suggesting that p53 represses hBD3 expression. A p53 binding site in the
      hBD3 gene promoter has been identified by using electrophoretic mobility shift
      assays and chromatin immunoprecipitation (ChIP). In addition, the p63 protein
      isoform DeltaNp63alpha, but not TAp63, stimulated transactivation of the hBD3
      gene and was co-expressed with hBD3 in head and neck cancer specimens. Therefore,
      high-risk HPV E6 oncoproteins may stimulate hBD3 expression in tumor cells to
      facilitate tumorigenesis of HPV-associated head and neck cancer. 

PMID- 27034007
TI  - Behavioral alterations following blood-brain barrier disruption stimulated by
      focused ultrasound.
AB  - The purpose of this study was to investigate the behavioral alterations and
      histological changes of the brain after FUS-induced BBB disruption (BBBD). Rats
      were behaviorally tested using the open field, hole-board, and grip strength
      tests from day 1 through day 32 after undergoing BBBD induced by FUS with either
      a mild or heavy parameter. In the open field test, we found an increase in center
      entries on day 1 and day 9 following heavy FUS treatment and a decrease in center
      entries at day 18 following mild FUS treatment. With regard to memory-related
      alterations, rats subjected to heavy FUS treatment exhibited longer latency to
      start exploring and to find the first baited hole. However, rats subjected to
      mild FUS treatment exhibited no significant differences in terms of memory
      performance or grip force. The obtained data suggest that heavy FUS treatment
      might induce hyperactivity, spatial memory impairment, and forelimb gripping
      deficits. Furthermore, while mild FUS treatment may have an impact on anxiety
      related behaviors, the data suggested it had no impact on locomotor activity,
      memory, or grip force. Thus, the behavioral alterations following FUS-induced
      BBBD require further investigation before clinical application. 

PMID- 27034009
TI  - The degree of intratumor mutational heterogeneity varies by primary tumor sub
      site.
AB  - In an era where mutational profiles inform treatment options, it is critical to
      know the extent to which tumor biopsies represent the molecular profile of the
      primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise
      primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive
      therapy the 5-year survival rate is at 50%. The primary objective of this study
      is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We
      used multi-region sequencing of paired primary and metastatic tumor DNA of 24
      spatially distinct samples from seven patients with HNSCC of larynx, floor of the
      mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes
      implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2%
      unique SNVs between the paired primary and metastatic lesions. In contrast, the
      oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition,
      HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These
      findings were validated on the Affymetrix whole genome 6.0 array platform and
      were consistent with data from The Cancer Genome Atlas (TCGA). This is the first
      report demonstrating differences in mutational heterogeneity varying by subsite
      in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an
      underestimation of the genetic abnormalities within tumors and may foster
      resistance to standard treatment protocols. These findings are relevant to
      investigators and clinicians developing personalized cancer treatments based on
      identification of specific mutations in tumor biopsies. 

PMID- 27034010
TI  - Molecular classification of cancer with the 92-gene assay in cytology and limited
      tissue samples.
AB  - BACKGROUND: Detailed molecular evaluation of cytology and limited tissue samples
      is increasingly becoming the standard for cancer care. Reproducible and accurate
      diagnostic approaches with reduced demands on cellularity are an ongoing unmet
      need. This study evaluated the performance of a 92-gene assay for molecular
      diagnosis of tumor type/subtype in cytology and limited tissue samples. METHODS:
      Clinical validation of accuracy for the 92-gene assay in limited tissue samples
      such as cytology cell blocks, core biopsies and small excisions was conducted in
      a blinded multi-institutional study (N = 109, 48% metastatic, 53% grade II and
      III). Analytical success rate and diagnostic utility were evaluated in a
      consecutive series of 644 cytology cases submitted for clinical testing. RESULTS:
      The 92-gene assay demonstrated 91% sensitivity (95% CI [0.84, 0.95]) for tumor
      classification, with high accuracy maintained irrespective of specimen type
      (100%, 92%, and 86% in FNA/cytology cell blocks, core biopsies, and small
      excisions, respectively; p = 0.26). The assay performed equally well for
      metastatic versus primary tumors (90% vs 93%, p = 0.73), and across histologic
      grades (100%, 90%, 89%, in grades I, II, and III, respectively; p = 0.75). In the
      clinical case series, a molecular diagnosis was reported in 87% of the 644
      samples, identifying 23 different tumor types and allowing for additional
      mutational analysis in selected cases. CONCLUSIONS: These findings demonstrate
      high accuracy and analytical success rate of the 92-gene assay, supporting its
      utility in the molecular diagnosis of cancer for specimens with limited tissue.

PMID- 27034008
TI  - The biology of DHX9 and its potential as a therapeutic target.
AB  - DHX9 is member of the DExD/H-box family of helicases with a "DEIH" sequence at
      its eponymous DExH-box motif. Initially purified from human and bovine cells and
      identified as a homologue of the Drosophila Maleless (MLE) protein, it is an NTP
      dependent helicase consisting of a conserved helicase core domain, two double
      stranded RNA-binding domains at the N-terminus, and a nuclear transport domain
      and a single-stranded DNA-binding RGG-box at the C-terminus. With an ability to
      unwind DNA and RNA duplexes, as well as more complex nucleic acid structures,
      DHX9 appears to play a central role in many cellular processes. Its functions
      include regulation of DNA replication, transcription, translation, microRNA
      biogenesis, RNA processing and transport, and maintenance of genomic stability.
      Because of its central role in gene regulation and RNA metabolism, there are
      growing implications for DHX9 in human diseases and their treatment. This review
      will provide an overview of the structure, biochemistry, and biology of DHX9, its
      role in cancer and other human diseases, and the possibility of targeting DHX9 in
      chemotherapy.

PMID- 27034011
TI  - Curcumin elevates sirtuin level but does not postpone in vitro senescence of
      human cells building the vasculature.
AB  - It is believed that curcumin, a component of the turmeric that belongs to
      hormetins, possesses anti-aging propensity. This property of curcumin can be
      partially explained by its influence on the level of sirtuins. Previously, we
      have shown that relatively high (2.5-10 uM) doses of curcumin induce senescence
      of cancer cells and cells building the vasculature. In the present study we
      examined whether curcumin at low doses (0.1 and 1 uM) is able to delay cell
      senescence and upregulate the level of sirtuins in human cells building the
      vasculature, namely vascular smooth muscle (VSMC) and endothelial (EC) cells. To
      this end we used cells senescing in a replicative and premature manner. We showed
      that low doses of curcumin in case of VSMC neither postponed the replicative
      senescence nor protected from premature senescence induced by doxorubicin.
      Moreover, curcumin slightly accelerated replicative senescence of EC. Despite
      some fluctuations, a clear increasing tendency in the level of sirtuins was
      observed in curcumin-treated young, senescing or already senescent cells. Sirtuin
      activation could be caused by the activation of AMPK resulting from superoxide
      elevation and ATP reduction. Our results show that curcumin at low doses can
      increase the level of sirtuins without delaying senescence of VSMC. 

PMID- 27034012
TI  - Capsules of virulent pneumococcal serotypes enhance formation of neutrophil
      extracellular traps during in vivo pathogenesis of pneumonia.
AB  - Neutrophil extracellular traps (NETs) are released by activated neutrophils to
      ensnare and kill microorganisms. NETs have been implicated in tissue injury since
      they carry cytotoxic components of the activated neutrophils. We have previously
      demonstrated the generation of NETs in infected murine lungs during both primary
      pneumococcal pneumonia and secondary pneumococcal pneumonia after primary
      influenza. In this study, we assessed the correlation of pneumococcal capsule
      size with pulmonary NETs formation and disease severity. We compared NETs
      formation in the lungs of mice infected with three pneumococcal strains of
      varying virulence namely serotypes 3, 4 and 19F, as well as a capsule-deficient
      mutant of serotype 4. In primary pneumonia, NETs generation was strongly
      associated with the pneumococcal capsule thickness, and was proportional to the
      disease severity. Interestingly, during secondary pneumonia after primary
      influenza infection, intense pulmonary NETs generation together with elevated
      myeloperoxidase activity and cytokine dysregulation determined the disease
      severity. These findings highlight the crucial role played by the size of
      pneumococcal capsule in determining the extent of innate immune responses such as
      NETs formation that may contribute to the severity of pneumonia. 

PMID- 27034013
TI  - Liang-Ge-San, a classic traditional Chinese medicine formula, protects against
      lipopolysaccharide-induced inflammation through cholinergic anti-inflammatory
      pathway.
AB  - Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is
      widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in
      clinic. However, the underlying mechanisms remain poorly defined. In this study,
      we discovered that LGS exerted potent anti-inflammatory effects in
      lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly
      depressed the production of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7
      macrophage cells. The degradation and phosphorylation of IkappaBalpha and the
      nuclear translocation of NF-kappaB p65 were also inhibited. Moreover, LGS
      activated alpha7 nicotinic cholinergic receptor (alpha7nAchR). The blockage of
      alpha7nAchR by selective inhibitor methyllycaconitine (MLA) or alpha7nAchR siRNA
      attenuated the inhibitory effects of LGS on IkappaBalpha, NF-kappaB p65, IL-6 and
      TNF-alpha. Critically, LGS significantly inhibited inflammation in LPS-induced
      ALI rats through the activation of NF-kappaB signaling pathway. However, these
      protective effects could be counteracted by the treatment of MLA. Taken together,
      we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo
      through cholinergic anti-inflammatory pathway. The study provides a rationale for
      the clinical application of LGS as an anti-inflammatory agent and supports the
      critical role of cholinergic anti-inflammatory pathway in inflammation. 

PMID- 27034014
TI  - Epithelial-to-endothelial transition and cancer stem cells: two cornerstones of
      vasculogenic mimicry in malignant tumors.
AB  - Vasculogenic mimicry (VM) is a functional microcirculation pattern in malignant
      tumors accompanied by endothelium-dependent vessels and mosaic vessels. VM has
      been identified in more than 15 solid tumor types and is associated with poor
      differentiation, late clinical stage and poor prognosis. Classic anti-angiogenic
      agents do not target endothelium-dependent vessels and are not efficacious
      against tumors exhibiting VM. Further insight into the molecular signaling that
      triggers and promotes VM formation could improve anti-angiogenic therapeutics.
      Recent studies have shown that cancer stem cells (CSCs) and epithelium-to
      endothelium transition (EET), a subtype of epithelial-to-mesenchymal transition
      (EMT), accelerate VM formation by stimulating tumor cell plasticity, remodeling
      the extracellular matrix (ECM) and connecting VM channels with host blood
      vessels. VM channel-lining cells originate from CSCs due to expression of EMT
      inducers such as Twist1, which promote EET and ECM remodeling. Hypoxia and high
      interstitial fluid pressure in the tumor microenvironment induce a specific type
      of cell death, linearly patterned programmed cell necrosis (LPPCN), which
      spatially guides VM and endothelium-dependent vessel networks. This review
      focuses on the roles of CSCs and EET in VM, and on possible novel anti-angiogenic
      strategies against alternative tumor vascularization.

PMID- 27034015
TI  - Photo-induced reduction of graphene oxide coating on optical waveguide and
      consequent optical intermodulation.
AB  - Increased absorption of transverse-magnetic (TM)-polarised light by a graphene
      oxide (GO) coated polymer waveguide has been observed in the presence of
      transverse-electric (TE)-polarised light. The GO-coated waveguide exhibits very
      strong photo-absorption of TE-polarised light--and acts as a TM-pass waveguide
      polariser. The absorbed TE-polarised light causes a significant temperature
      increase in the GO film and induces thermal reduction of the GO, resulting in an
      increase in optical-frequency conductivity and consequently increased optical
      propagation loss. This behaviour in a GO-coated waveguide gives the action of an
      inverted optical switch/modulator. By varying the incident TE-polarised light
      power, a maximum modulation efficiency of 72% was measured, with application of
      an incident optical power level of 57 mW. The GO-coated waveguide was able to
      respond clearly to modulated TE-polarised light with a pulse duration of as
      little as 100 MUs. In addition, no wavelength dependence was observed in the
      response of either the modulation (TE-polarised light) or the signal (TM
      polarised light).

PMID- 27034016
TI  - Clinical effectiveness and cost-effectiveness of interventions for the treatment
      of anogenital warts: systematic review and economic evaluation.
AB  - BACKGROUND: Typically occurring on the external genitalia, anogenital warts
      (AGWs) are benign epithelial skin lesions caused by human papillomavirus
      infection. AGWs are usually painless but can be unsightly and physically
      uncomfortable, and affected people might experience psychological distress. The
      evidence base on the clinical effectiveness and cost-effectiveness of treatments
      for AGWs is limited. OBJECTIVES: To systematically review the evidence on the
      clinical effectiveness of medical and surgical treatments for AGWs and to develop
      an economic model to estimate the cost-effectiveness of the treatments. DATA
      SOURCES: Electronic databases (MEDLINE, MEDLINE In-Process & Other Non-Indexed
      Citations, EMBASE, The Cochrane Library databases and Web of Science) were
      searched from inception (or January 2000 for Web of Science) to September 2014.
      Bibliographies of relevant systematic reviews were hand-searched to identify
      potentially relevant studies. The World Health Organization International
      Clinical Trials Registry Platform and ClinicalTrials.gov were searched for
      ongoing and planned studies. REVIEW METHODS: A systematic review of the clinical
      effectiveness literature was carried out according to standard methods and a
      mixed-treatment comparison (MTC) undertaken. The model implemented for each
      outcome was that with the lowest deviance information criterion. A de novo
      economic model was developed to assess cost-effectiveness from the perspective of
      the UK NHS. The model structure was informed through a systematic review of the
      economic literature and in consultation with clinical experts. Effectiveness data
      were obtained from the MTC. Costs were obtained from the literature and standard
      UK sources. RESULTS: Of 4232 titles and abstracts screened for inclusion in the
      review of clinical effectiveness, 60 randomised controlled trials (RCTs)
      evaluating 19 interventions were included. Analysis by MTC indicated that
      ablative techniques were typically more effective than topical interventions at
      completely clearing AGWs at the end of treatment. Podophyllotoxin 0.5% solution
      (Condyline((r)), Takeda Pharmaceutical Company Ltd; Warticon((r)) solution,
      Stiefel Laboratories Ltd) was found to be the most effective topical treatment
      evaluated. Networks for other outcomes included fewer treatments, which restrict
      conclusions on the comparative effectiveness of interventions. In total, 84
      treatment strategies were assessed using the economic model. Podophyllotoxin 0.5%
      solution first line followed by carbon dioxide (CO2) laser therapy second line if
      AGWs did not clear was most likely to be considered a cost-effective use of
      resources at a willingness to pay of L20,000-30,000 per additional quality
      adjusted life-year gained. The result was robust to most sensitivity analyses
      conducted. LIMITATIONS: Limited reporting in identified studies of baseline
      characteristics for the enrolled population generates uncertainty around the
      comparability of the study populations and therefore the generalisability of the
      results to clinical practice. Subgroup analyses were planned based on type,
      number and size of AGWs, all of which are factors thought to influence treatment
      effect. Lack of data on clinical effectiveness based on these characteristics
      precluded analysis of the differential effects of treatments in the subgroups of
      interest. Despite identification of 60 studies, most comparisons in the MTC are
      informed by only one RCT. Additionally, lack of head-to-head RCTs comparing key
      treatments, together with minimal reporting of results in some studies, precluded
      comprehensive analysis of all treatments for AGWs. CONCLUSIONS: The results
      generated by the MTC are in agreement with consensus opinion that ablative
      techniques are clinically more effective at completely clearing AGWs after
      treatment. However, the evidence base informing the MTC is limited. A head-to
      head RCT that evaluates the comparative effectiveness of interventions used in
      clinical practice would help to discern the potential advantages and
      disadvantages of the individual treatments. The results of the economic analysis
      suggest that podophyllotoxin 0.5% solution is likely to represent a cost
      effective first-line treatment option. More expensive effective treatments, such
      as CO2 laser therapy or surgery, may represent cost-effective second-line
      treatment options. No treatment and podophyllin are unlikely to be considered
      cost-effective treatment options. There is uncertainty around the cost
      effectiveness of treatment with imiquimod, trichloroacetic acid and cryotherapy.
      STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005457. FUNDING:
      The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 27034017
TI  - HOXB13 and other high penetrant genes for prostate cancer.

PMID- 27034018
TI  - Alcoholic beverage intake throughout the week and contribution to dietary energy
      intake in Australian adults.
AB  - OBJECTIVE: To assess alcoholic beverage intake among Australian adults and its
      contribution to dietary energy intake. DESIGN: Secondary analysis of a national
      dietary survey using 24 h dietary recall. SETTING: Australian National Nutrition
      and Physical Activity Survey (NNPAS) conducted from May 2011 to June 2012.
      SUBJECTS: Adults (n 9341) aged 19 years and over. RESULTS: On the day preceding
      the survey, 32.8% of Australian adults consumed one or more alcoholic drinks. The
      median contribution to total energy intake for consumers did not differ
      significantly between males and females (13.7% and 12.9%, respectively; P=0.10).
      The prevalence of consumption of alcoholic drinks on Friday, Saturday and Sunday
      was 38.8 (95% CI 37.1, 40.5)%, higher than the other days (28.6 (95% CI 27.5,
      29.8)%). Consumers had a median daily intake of 4.0 standard drinks on the
      weekend compared with 3.0 standard drinks during the week (P<0.001). Beer was the
      most commonly consumed alcoholic beverage for men and white wine for women. The
      highest prevalence of alcoholic beverage intake occurred in the highest quintile
      of adjusted household income (42.7 (95% CI 40.4, 45.0)%) and the 'overweight' BMI
      category (40.3 (95% CI 38.5, 42.0)%). Alcoholic beverage intake among consumers
      was significantly different by household income quintile (median 3.84 (highest)
      v. 3.05 standard drinks (lowest); P<0.05) and by waist circumference category
      (median 4.09 standard drinks (highest)). CONCLUSIONS: Alcoholic drinks contribute
      substantially to the dietary energy intake of Australian adults. The type and
      pattern of consumption of alcoholic beverage intake should be considered in the
      development of strategies to improve dietary intake.

PMID- 27034019
TI  - Complete genome sequence of opine-utilizing Variovorax sp. strain PAMC28711
      isolated from an Antarctic lichen.
AB  - We report the complete genome sequence of Variovorax sp. strain PAMC28711
      isolated from the Antarctic lichen Himantormia sp. Whole genome sequencing
      revealed opine oxidase- and octopine dehydrogenase-related gene clusters that are
      involved in octopine utilization. These data will lead to future genetic and
      biochemical studies on the unusual catabolic traits of opine and octopine
      utilization in extremely cold environments. 

PMID- 27034020
TI  - Analysis and optimization of triacylglycerol synthesis in novel oleaginous
      Rhodococcus and Streptomyces strains isolated from desert soil.
AB  - As oleaginous microorganisms represent an upcoming novel feedstock for the
      biotechnological production of lipids or lipid-derived biofuels, we searched for
      novel, lipid-producing strains in desert soil. This was encouraged by the
      hypothesis that neutral lipids represent an ideal storage compound, especially
      under arid conditions, as several animals are known to outlast long periods in
      absence of drinking water by metabolizing their body fat. Ten lipid-accumulating
      bacterial strains, affiliated to the genera Bacillus, Cupriavidus, Nocardia,
      Rhodococcus and Streptomyces, were isolated from arid desert soil due to their
      ability to synthesize poly(beta-hydroxybutyrate), triacylglycerols or wax esters.
      Particularly two Streptomyces sp. strains and one Rhodococcus sp. strain
      accumulate significant amounts of TAG under storage conditions under optimized
      cultivation conditions. Rhodococcus sp. A27 and Streptomyces sp. G49 synthesized
      approx. 30% (w/w) fatty acids from fructose or cellobiose, respectively, while
      Streptomyces isolate G25 reached a cellular fatty acid content of nearly 50%
      (w/w) when cultivated with cellobiose. The stored triacylglycerols were composed
      of 30-40% branched fatty acids, such as anteiso-pentadecanoic or iso-hexadecanoic
      acid. To date, this represents by far the highest lipid content described for
      streptomycetes. A biotechnological production of such lipids using
      (hemi)cellulose-derived raw material could be used to obtain sustainable
      biodiesel with a high proportion of branched-chain fatty acids to improve its
      cold-flow properties and oxidative stability. 

PMID- 27034021
TI  - Complete genome sequence of Burkholderia sp. strain PAMC28687, a potential
      octopine-utilizing bacterium isolated from Antarctica lichen.
AB  - We report the complete genome sequence of Burkholderia sp. PAMC28687, which was
      isolated from the Antarctica lichen Useea sp., for better understanding of its
      catabolic traits in utilizing octopine as a source of carbon/nitrogen between
      Burkholderia and lichen. The genome consists of three circular chromosomes with
      five circular plasmids for the total 6,881,273bp sized genome with a G+C content
      of 58.14%. 

PMID- 27034022
TI  - Complete genome of Zhongshania aliphaticivorans SM-2(T), an aliphatic hydrocarbon
      degrading bacterium isolated from tidal flat sediment.
AB  - Zhongshania aliphaticivorans SM-2(T), a degrader of aliphatic hydrocarbons, is a
      Gram-negative, rod-shaped, flagellated, facultatively aerobic bacterium. Here, we
      report the genome sequence of strain SM-2(T), which has a size of 4,204,359bp
      with 44 tRNAs, 9 rRNAs, and 3664 protein-coding genes. In addition, several genes
      encoding aliphatic hydrocarbon degraders (alkane 1-monooxygenase, haloalkane
      dehalogenase, and cytochrome P450) were detected in the genome shedding light on
      the function of pollutants degradation. 

PMID- 27034023
TI  - Complete genome sequence of Frondihabitans sp. strain PAMC28766, a novel
      carotenoid-producing and radiation-resistant strain isolated from an Antarctic
      lichen.
AB  - Here, we report the first complete genome sequence of Frondihabitans sp. strain
      PAMC28766, which was found to consist of three plasmids, one chromosome
      (4,345,897bp), and a series of genes involved in carotenoid biosynthesis and
      nucleotide excision repair. An analysis of the Frondihabitans sp. PAMC28766
      genome will improve our understanding of the carotenoid biosynthesis pathway.
      Furthermore, the sequence data will provide novel insight into UV radiation
      resistance in extremely cold environments. 

PMID- 27034024
TI  - Voxel-based morphometry in opera singers: Increased gray-matter volume in right
      somatosensory and auditory cortices.
AB  - In contrast to instrumental musicians, professional singers do not train on a
      specific instrument but perfect a motor system that has already been extensively
      trained during speech motor development. Previous functional imaging studies
      suggest that experience with singing is associated with enhanced somatosensory
      based vocal motor control. However, experience-dependent structural plasticity in
      vocal musicians has rarely been studied. We investigated voxel-based morphometry
      (VBM) in 27 professional classical singers and compared gray matter volume in
      regions of the "singing-network" to an age-matched group of 28 healthy volunteers
      with no special singing experience. We found right hemispheric volume increases
      in professional singers in ventral primary somatosensory cortex (larynx S1) and
      adjacent rostral supramarginal gyrus (BA40), as well as in secondary
      somatosensory (S2) and primary auditory cortices (A1). Moreover, we found that
      earlier commencement with vocal training correlated with increased gray-matter
      volume in S1. However, in contrast to studies with instrumental musicians, this
      correlation only emerged in singers who began their formal training after the age
      of 14years, when speech motor development has reached its first plateau.
      Structural data thus confirm and extend previous functional reports suggesting a
      pivotal role of somatosensation in vocal motor control with increased experience
      in singing. Results furthermore indicate a sensitive period for developing
      additional vocal skills after speech motor coordination has matured.

PMID- 27034025
TI  - Differential effect of age on posterior and anterior hippocampal functional
      connectivity.
AB  - Aging is associated with declines in cognitive performance and multiple changes
      in the brain, including reduced default mode functional connectivity (FC).
      However, conflicting results have been reported regarding age differences in FC
      between hippocampal and default mode regions. This discrepancy may stem from the
      variation in selection of hippocampal regions. We therefore examined the effect
      of age on resting state FC of anterior and posterior hippocampal regions in an
      adult life-span sample. Advanced age was associated with lower FC between the
      posterior hippocampus and three regions: the posterior cingulate cortex, medial
      prefrontal cortex, and lateral parietal cortex. In addition, age-related
      reductions of FC between the left and right posterior hippocampus, and
      bilaterally along the posterior to anterior hippocampal axis were noted. Age
      differences in medial prefrontal and inter-hemispheric FC significantly differed
      between anterior and posterior hippocampus. Older age was associated with lower
      performance in all cognitive domains, but we observed no associations between FC
      and cognitive performance after controlling for age. We observed a significant
      effect of gender and a linear effect of COMT val158met polymorphism on
      hippocampal FC. Females showed higher FC of anterior and posterior hippocampus
      and medial prefrontal cortex than males, and the dose of val allele was
      associated with lower posterior hippocampus - posterior cingulate FC, independent
      of age. Vascular and metabolic factors showed no significant effects on FC. These
      results suggest differential age-related reduction in the posterior hippocampal
      FC compared to the anterior hippocampus, and an age-independent effect of gender
      and COMT on hippocampal FC.

PMID- 27034026
TI  - AMPK activators: mechanisms of action and physiological activities.
AB  - AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis,
      which coordinates metabolic pathways and thus balances nutrient supply with
      energy demand. Because of the favorable physiological outcomes of AMPK activation
      on metabolism, AMPK has been considered to be an important therapeutic target for
      controlling human diseases including metabolic syndrome and cancer. Thus,
      activators of AMPK may have potential as novel therapeutics for these diseases.
      In this review, we provide a comprehensive summary of both indirect and direct
      AMPK activators and their modes of action in relation to the structure of AMPK.
      We discuss the functional differences among isoform-specific AMPK complexes and
      their significance regarding the development of novel AMPK activators and the
      potential for combining different AMPK activators in the treatment of human
      disease. 

PMID- 27034027
TI  - Myosin heavy chain is stabilized by BCL-2 interacting cell death suppressor (BIS)
      in skeletal muscle.
AB  - BCL-2 interacting cell death suppressor (BIS), which is ubiquitously expressed,
      has important roles in various cellular processes, such as apoptosis, the
      cellular stress response, migration and invasion and protein quality control. In
      particular, BIS is highly expressed in skeletal and cardiac muscles, and BIS gene
      mutations result in human myopathy. In this study, we show that mRNA and protein
      levels of BIS were markedly increased during skeletal myogenesis in C2C12 cells
      and mouse satellite cells. BIS knockdown did not prevent the early stage of
      skeletal myogenesis, but did induce muscle atrophy and a decrease in the diameter
      of myotubes. BIS knockdown significantly suppressed the expression level of
      myosin heavy chain (MyHC) without changing the expression levels of myogenic
      marker proteins, such as Mgn, Cav-3 and MG53. In addition, BIS endogenously
      interacted with MyHC, and BIS knockdown induced MyHC ubiquitination and
      degradation. From these data, we conclude that molecular association of MyHC and
      BIS is necessary for MyHC stabilization in skeletal muscle. 

PMID- 27034028
TI  - Peat Bogs as Hotspots for Organoarsenical Formation and Persistence.
AB  - Peatlands have received significant atmospheric inputs of As and S since the
      onset of the Industrial Revolution, but the effect of S deposition on the fate of
      As is largely unknown. It may encompass the formation of As sulfides and
      organosulfur-bound As, or the indirect stimulation of As biotransformation
      processes, which are presently not considered as important As immobilization
      pathways in wetlands. To investigate the immobilization mechanisms of
      anthropogenically derived As in peatlands subjected to long-term atmospheric
      pollution, we explored the solid-phase speciation of As, Fe, and S in English
      peat bogs by X-ray absorption spectroscopy. Additionally, we analyzed the
      speciation of As in pore- and streamwaters. Linear combination fits of extended X
      ray absorption fine structure (EXAFS) data imply that 62-100% (average: 82%) of
      solid-phase As (Astot: 9-92 mg/kg) was present as organic As(V) and As(III). In
      agreement with appreciable concentrations of organoarsenicals in surface waters
      (pH: 4.0-4.4, Eh: 165-190 mV, average Astot: 1.5-129 MUg/L), our findings reveal
      extensive biotransformation of atmospheric As and the enrichment of
      organoarsenicals in the peat, suggesting that the importance of
      organometal(loid)s in wetlands subjected to prolonged air pollution is higher
      than previously assumed.

PMID- 27034029
TI  - ROLE OF SURFACE WOUNDS AND BROWN ALGAL EPIPHYTES IN THE COLONIZATION OF
      ASCOPHYLLUM NODOSUM (PHAEOPHYCEAE) FRONDS BY VERTEBRATA LANOSA (RHODOPHYTA)(1).
AB  - Ascophyllum nodosum (L.) Le Jol. forms extensive beds in wave-sheltered, rocky
      intertidal habitats on the northwestern Atlantic coast. This fucoid seaweed is
      host to an obligate red algal epiphyte, Vertebrata lanosa (L.) T. A. Chr.
      [=Polysiphonia lanosa (L.) Tandy], and two facultative brown algal epiphytes,
      Elachista fucicola (Velley) Aresch. and Pylaiella littoralis (L.) Kjellm.
      Although V. lanosa can occur throughout most of the length of host fronds, it
      largely predominates in midfrond segments. The two brown algal epiphytes are
      restricted to distal segments. Through field experiments conducted in Nova
      Scotia, Canada, we tested the hypothesis that surface wounds are required for the
      colonization of distal segments of host fronds by V. lanosa. Distal tissues
      normally have a smooth surface because of their young age (A. nodosum fronds grow
      apically). By creating small wounds that mimicked grazing wounds distributed
      elsewhere on host fronds, we demonstrated that V. lanosa can colonize distal
      frond segments during the growth and reproductive season (summer and autumn).
      Approximately half of the artificial wounds were colonized by V. lanosa during
      this time. The experimental exclusion of both brown algal epiphytes from distal
      frond segments did not affect colonization by V. lanosa. Thus, we conclude that
      the absence of surface irregularities on distal segments of host fronds,
      specifically small wounds, is the main factor explaining the absence of V. lanosa
      there. We propose that further experimental work clarifying epiphyte distribution
      in host beds will enhance our ability to understand the functional role of
      epiphytes in intertidal ecosystems. 

PMID- 27034030
TI  - PULSES OF PHOSPHATE PROMOTE DOMINANCE OF THE TOXIC CYANOPHYTE CYLINDROSPERMOPSIS
      RACIBORSKII IN A SUBTROPICAL WATER RESERVOIR(1).
AB  - The role of dissolved inorganic phosphorus (DIP) in promoting dominance of the
      toxic nitrogen (N)-fixing cyanobacterium Cylindrospermopsis raciborskii (Wolosz.)
      Seenayya et Subba Raju was examined in a subtropical water reservoir, Lake
      Samsonvale (=North Pine reservoir). A novel in situ bioassay approach, using
      dialysis tubing rather than bottles or bags, was used to determine the change in
      C. raciborskii dominance with daily additions of DIP. A statistically significant
      increase in dominance of C. raciborskii was observed when DIP was added at two
      concentrations (0.32 MUM and 16 MUM) in a daily pulse over a 4 d period in three
      separate experiments in the summer of 2006/2007. There was an increase in both C.
      raciborskii cell concentrations and biovolume in two DIP treatments, but not in
      the ammoniacal N + DIP treatment. In addition, overall phytoplankton cell
      concentrations increased with DIP addition, indicating that Lake Samsonvale was
      DIP limited at the time of experiments. Given the bioassay response, it is likely
      that dominance of C. raciborskii could increase in Lake Samsonvale with periodic
      injections of DIP such as inflow events. 

PMID- 27034031
TI  - EFFECT OF TEMPERATURE AND GRAZING ON GROWTH AND REPRODUCTION OF FLOATING
      MACROCYSTIS SPP. (PHAEOPHYCEAE) ALONG A LATITUDINAL GRADIENT(1).
AB  - Macroalgal rafts frequently occur floating in coastal waters of temperate regions
      of the world's oceans. These rafts are considered important dispersal vehicles
      for associated organisms with direct development. However, environmental factors
      may limit the floating potential of kelp and thereby the dispersal of associated
      organisms. To examine the effect of water temperature and grazing on growth,
      reproductive output, and survival of floating Macrocystis spp., experiments were
      conducted in outdoor tanks during austral summer 2006/2007 at three sites along
      the Chilean Pacific coast (20 degrees  S, 30 degrees  S, 40 degrees  S). At each
      site, Macrocystis spp. was maintained individually at three different water
      temperatures (ambient, ambient - 4 degrees C, ambient + 4 degrees C) and in the
      presence or absence of the amphipod grazer Peramphithoe femorata for 14 d. High
      water temperatures (>20 degrees C) provoked rapid degradation of Macrocystis spp.
      rafts. At moderate temperatures (15 degrees C-20 degrees C), algal survival
      depended on the presence of associated grazers. In the absence of grazers, algal
      rafts gained in biomass while grazing caused considerable losses of algal
      biomass. Algal survival was the highest under cooler conditions (<15 degrees C),
      where raft degradation was slow and grazer-induced biomass losses were
      compensated by continuing algal growth. Our results indicate that floating kelp
      rafts can survive for long time periods at the sea surface, but survival depends
      on the interaction between temperature and grazing. We suggest that these
      processes limiting the survival of kelp rafts in warmer temperatures may act as a
      dispersal barrier for kelp and its associated passengers. 

PMID- 27034032
TI  - FOURIER TRANSFORM INFRARED MICROSPECTROSCOPY AS A TOOL TO IDENTIFY MACROALGAL
      PROPAGULES(1).
AB  - Understanding of macroalgal dispersal has been hindered by the difficulty in
      identifying propagules. Different carrageenans typically occur in gametophytes
      and tetrasporophytes of the red algal family Gigartinaceae, and we may expect
      that carpospores and tetraspores also differ in composition of carrageenans.
      Using Fourier transform infrared (FT-IR) microspectroscopy, we tested the model
      that differences in carrageenans and other cellular constituents between nuclear
      phases should allow us to discriminate carpospores and tetraspores of Chondrus
      verrucosus Mikami. Spectral data suggest that carposporophytes isolated from the
      pericarp and female gametophytes contained kappa-carrageenan, whereas
      tetrasporophytes contained lambda-carrageenan. However, both carpospores and
      tetraspores exhibited absorbances in wave bands characteristic of kappa-, iota-,
      and lambda-carrageenans. Carpospores contained more proteins and may be more
      photosynthetically active than tetraspores, which contained more lipid reserves.
      We draw analogies to planktotrophic and lecithotrophic larvae. These differences
      in cellular chemistry allowed reliable discrimination of spores, but pretreatment
      of spectral data affected the accuracy of classification. The best classification
      of spores was achieved with extended multiplicative signal correction (EMSC)
      pretreatment using partial least squares discrimination analysis, with correct
      classification of 86% of carpospores and 83% of tetraspores. Classification may
      be further improved by using synchrotron FT-IR microspectroscopy because of its
      inherently higher signal-to-noise ratio compared with microspectroscopy using
      conventional sources of IR. This study demonstrates that FT-IR microspectroscopy
      and bioinformatics are useful tools to advance our understanding of algal
      dispersal ecology through discrimination of morphologically similar propagules
      both within and potentially between species. 

PMID- 27034033
TI  - BIOLOGICAL WEIGHTING FUNCTIONS FOR UV INHIBITION OF PHOTOSYNTHESIS IN THE KELP
      LAMINARIA HYPERBOREA (PHAEOPHYCEAE)(1).
AB  - Different wavelengths of sunlight either drive or inhibit macroalgal production.
      Ultraviolet radiation (UVR) effectively disrupts photosynthesis, but since UVR is
      rapidly absorbed in coastal waters, macroalgal photoinhibition and tolerance to
      UVR depend on the depth of attachment and acclimation state of the individual.
      The inhibition response to UVR is quantified with a biological weighting function
      (BWF), a spectrum of empirically derived weights that link irradiance at a
      specific wavelength to overall biological effect. We determined BWFs for shallow
      (0 m, mean low water [MLW]) and deep (10 m) Laminaria hyperborea (Gunnerus)
      Foslie collected off the island of Finnoy, Norway. For each replicate sporophyte,
      we concurrently measured both O2 evolution and (13) C uptake in 48 different
      light treatments, which varied in UV spectral composition and irradiance. The
      relative shape of the kelp BWF was most similar to that of a land plant, and the
      absolute spectral weightings and sensitivity were typically less than
      phytoplankton, particularly in the ultraviolet radiation A (UVA) region.
      Differences in BWFs between O2 and (13) C photosynthesis and between shallow
      (high light) and deep (low light) kelp were also most significant in the UVA.
      Because of its greater contribution to total incident irradiance, UVA was more
      important to daily loss of production in kelp than ultraviolet radiation B (UVB).
      Photosynthetic quotient (PQ) also decreased with increased UVR stress, and the
      magnitude of PQ decline was greater in deepwater kelp. Significantly, BWFs assist
      in the comparison of biological responses to experimental light sources versus in
      situ sunlight and are critical to quantifying kelp production in a changing
      irradiance environment. 

PMID- 27034034
TI  - RELEASE OF CARBOHYDRATES AND PROTEINS BY A SUBTROPICAL STRAIN OF RAPHIDIOPSIS
      BROOKII (CYANOBACTERIA) ABLE TO PRODUCE SAXITOXIN AT THREE NITRATE
      CONCENTRATIONS(1).
AB  - Raphidiopsis brookii P. J. Hill (cyanobacteria) was isolated from a small
      subtropical eutrophic pond (Bigua Pond) located in the grounds of Rio Grande
      University in the extreme south of Brazil, following a toxic bloom of this
      species. Growth, saxitoxin production, and release of carbohydrates and protein
      were monitored at three sodium nitrate concentrations (500, 1,000, and 1,500
      MUM), from inoculation up to the stationary growth phase. Growth was monitored by
      determining the biovolume, chl content, and trichome count. Growth was better
      described in terms of biovolume and chl measurements, because trichome
      fragmentation was observed to increase at the stationary growth phase.
      Carbohydrates and proteins were released in small amounts during most of the
      experiment, with a significant increase during the stationary phase.
      Extracellular polysaccharides were essentially composed of glucose, galactose, N
      acetyl-glucosamine, mannose, xylose, rhamnose, arabinose, and fucose. The
      relative proportions of these units showed no significant variation during
      growth. Small quantities of extracellular free carbohydrates were also detected,
      and only fucose was released in significant amounts at the lowest nitrate
      concentration (500 MUM). R. brookii produced both saxitoxin and dc-saxitoxin, the
      former at four times the rate of the latter. This was the first study
      demonstrating saxitoxin production and the release of both carbohydrate and
      protein by R. brookii. 

PMID- 27034035
TI  - LIGHT-INDUCED MOTILE RESPONSES OF THE ESTUARINE BENTHIC DIATOMS NAVICULA
      PERMINUTA AND CYLINDROTHECA CLOSTERIUM (BACILLARIOPHYCEAE)(1).
AB  - Motility of estuarine epipelic (mud-inhabiting) diatoms is an important
      adaptation to living in biofilms present within fine sediments. Motility allows
      cells to migrate within the photic zone in response to a wide range of
      environmental stimuli. The motile responses of two species of benthic diatoms to
      photon fluence rates and spectral quality were investigated. Cultures of Navicula
      perminuta (Grunow) in van Heurck and Cylindrotheca closterium (Ehrenb.) J. C.
      Lewin et Reimann both exhibited photoaccumulation at ~200 MUmol . m(-2)  . s(-1)
      and photodispersal from photon flux densities (PFDs) of ~15 MUmol . m(-2)  . s(
      1) . Photokinesis (changing cell speed) contributed toward photodispersal for
      both species, and red light (lambda = 681-691 nm) was most effective at inducing
      this process. N. perminuta showed a phototactic (directional) response, with
      active movement in response to a light gradient. Although this response was
      exhibited in white light, these directional responses were only elicited by
      wavelengths from 430 to 510 nm. In contrast, C. closterium did not exhibit
      phototaxis under any light conditions used in this study. Motile benthic diatoms
      thus exhibit complex and sophisticated responses to light quantity and quality,
      involving combinations of photokinesis and phototaxis, which can contribute
      toward explaining the patterns of large-scale cell movements observed in natural
      estuarine biofilms. 

PMID- 27034036
TI  - SENSITIVITY OF ANTARCTIC UROSPORA PENICILLIFORMIS (ULOTRICHALES, CHLOROPHYTA) TO
      ULTRAVIOLET RADIATION IS LIFE-STAGE DEPENDENT(1).
AB  - The sensitivity of different life stages of the eulittoral green alga Urospora
      penicilliformis (Roth) Aresch. to ultraviolet radiation (UVR) was examined in the
      laboratory. Gametophytic filaments and propagules (zoospores and gametes)
      released from filaments were separately exposed to different fluence of radiation
      treatments consisting of PAR (P = 400-700 nm), PAR + ultraviolet A (UVA) (PA, UVA
      = 320-400 nm), and PAR + UVA + ultraviolet B (UVB) (PAB, UVB = 280-320 nm).
      Photophysiological indices (ETRmax , Ek , and alpha) derived from rapid light
      curves were measured in controls, while photosynthetic efficiency and amount of
      DNA lesions in terms of cyclobutane pyrimidine dimers (CPDs) were measured after
      exposure to radiation treatments and after recovery in low PAR; pigments of
      propagules were quantified after exposure treatment only. The photosynthetic
      conversion efficiency (alpha) and photosynthetic capacity (rETRmax ) were higher
      in gametophytes compared with the propagules. The propagules were slightly more
      sensitive to UVB-induced DNA damage; however, both life stages of the eulittoral
      inhabiting turf alga were not severely affected by the negative impacts of UVR.
      Exposure to a maximum of 8 h UVR caused mild effects on the photochemical
      efficiency of PSII and induced minimal DNA lesions in both the gametophytes and
      propagules. Pigment concentrations were not significantly different between PAR
      exposed and PAR + UVR-exposed propagules. Our data showed that U. penicilliformis
      from the Antarctic is rather insensitive to the applied UVR. This amphi
      equatorial species possesses different protective mechanisms that can cope with
      high UVR in cold-temperate waters of both hemispheres and in polar regions under
      conditions of increasing UVR as a consequence of further reduction of
      stratospheric ozone. 

PMID- 27034037
TI  - TRANSCRIPTIONAL ANALYSIS OF THE UNICELLULAR, DIAZOTROPHIC CYANOBACTERIUM
      CYANOTHECE SP. ATCC 51142 GROWN UNDER SHORT DAY/NIGHT CYCLES(1).
AB  - Cyanothece sp. strain ATCC 51142 is a unicellular, diazotrophic cyanobacterium
      that demonstrates extensive metabolic periodicities of photosynthesis,
      respiration, and nitrogen fixation when grown under N2 -fixing conditions. We
      have performed a global transcription analysis of this organism using 6 h
      light:dark (L:D) cycles in order to determine the response of the cell to these
      conditions and to differentiate between diurnal and circadian-regulated genes. In
      addition, we used a context-likelihood of relatedness (CLR) analysis with these
      data and those from 2 d L:D and L:D plus continuous light experiments to better
      differentiate between diurnal and circadian-regulated genes. Cyanothece sp.
      acclimated in several ways to growth under short L:D conditions. Nitrogen was
      fixed in every second dark period and only once in each 24 h period. Nitrogen
      fixation was strongly correlated to the energy status of the cells and glycogen
      breakdown, and high respiration rates were necessary to provide appropriate
      energy and anoxic conditions for this process. We conclude that glycogen
      breakdown is a key regulatory step within these complex processes. Our results
      demonstrated that the main metabolic genes involved in photosynthesis,
      respiration, nitrogen fixation, and central carbohydrate metabolism have strong
      (or total) circadian-regulated components. The short L:D cycles enable us to
      identify transcriptional differences among the family of psbA genes, as well as
      the differing patterns of the hup genes, which follow the same pattern as
      nitrogenase genes, relative to the hox genes, which displayed a diurnal, dark
      dependent gene expression. 

PMID- 27034038
TI  - PATERNAL LEAKAGE OF MITOCHONDRIAL DNA IN A FUCUS (PHAEOPHYCEAE) HYBRID ZONE(1).
AB  - Eukaryotic mitochondria are mostly uniparentally (maternally) inherited, although
      mtDNA heteroplasmy has been reported in all major lineages. Heteroplasmy, the
      presence of more than one mitochondrial genome in an individual, can arise from
      recombination, point mutations, or by occasional transmission of the paternal
      mtDNA (=paternal leakage). Here, we report the first evidence of mtDNA paternal
      leakage in brown algae. In Denmark, where Fucus serratus L. and Fucus evanescens
      C. Agardh have hybridized for years, we found eight introgressed individuals that
      possessed the very distinct haplotypes of each parental species. The finding of
      heteroplasmy in individuals resulting from several generations of backcrosses
      suggests that paternal leakage occurred in earlier generations and has persisted
      through several meiotic bottlenecks. 

PMID- 27034039
TI  - UREASE GENE SEQUENCES FROM ALGAE AND HETEROTROPHIC BACTERIA IN AXENIC AND
      NONAXENIC PHYTOPLANKTON CULTURES(1).
AB  - While urea has long been recognized as an important form of nitrogen in
      planktonic ecosystems, very little is known about how many or which phytoplankton
      and bacteria can use urea as a nitrogen source. We developed a method, targeting
      the gene encoding urease, for the direct detection and identification of
      ureolytic organisms and tested it on seven axenic phytoplankton cultures (three
      diatoms, two prymnesiophytes, a eustigmatophyte, and a pelagophyte) and on three
      nonaxenic Aureococcus anophagefferens Hargraves et Sieburth cultures (CCMP1784
      and two CCMP1708 cultures from different laboratories). The urease amplicon
      sequences from axenic phytoplankton cultures were consistent with genomic data in
      the three species for which both were available. Seven of 12 phytoplankton
      species have one or more introns in the amplified region of their urease gene(s).
      The 63 urease amplicons that were cloned and sequenced from nonaxenic A.
      anophagefferens cultures grouped into 17 distinct sequence types. Eleven types
      were related to alpha-Proteobacteria, including three types likely belonging to
      the genus Roseovarius. Four types were related to gamma-Proteobacteria, including
      two likely belonging to the genus Marinobacter, and two types were related to
      beta-Proteobacteria. Terminal restriction fragment length polymorphism (TRFLP)
      analyses suggested that the sequenced amplicons represented approximately half of
      the diversity of bacterial urease genes present in the nonaxenic cultures. While
      many of the bacterial urease sequence types were apparently lab- or culture
      specific, others were found in all three nonaxenic cultures, suggesting the
      possibility of specific relationships between these bacteria and A.
      anophagefferens. 

PMID- 27034040
TI  - HIGH-LIGHT AND SODIUM CHLORIDE STRESS DIFFERENTIALLY REGULATE THE BIOSYNTHESIS OF
      ASTAXANTHIN IN CHLORELLA ZOFINGIENSIS (CHLOROPHYCEAE)(1).
AB  - Although light and salt stresses are known to enhance the biosynthesis of
      astaxanthin in certain green algae, the mechanism of their action remains largely
      unknown. Here we report the regulation of the genes encoding phytoene desaturase
      (PDS), carotenoid hydroxylase (CHYb), and carotenoid ketolase (BKT) in the green
      alga Chlorella zofingiensis Donz under light or sodium chloride (NaCl) stress.
      High-light illumination (150 MUmol photons . m(-2)  . s(-1) ) up-regulated the
      transcripts of PDS, CHYb, and BKT and greatly enhanced the biosynthesis of
      zeaxanthin, canthaxanthin, and astaxanthin. In contrast, sodium chloride stress
      only up-regulated the transcript of BKT and enhanced the biosynthesis of
      canthaxanthin and astaxanthin. High-light and NaCl stresses were revealed to
      result in an increase in the intracellular reactive oxygen species (ROS) level.
      By applying chemically generated ROS to the algal cells, we determined that (1)
      O2 specifically up-regulated the CHYb gene, whereas *OH up-regulated the PDS and
      BKT genes. We suggest that high-light and NaCl stresses may stimulate the
      generation of different ROS, which in turn trigger the up-regulation of specific
      carotenogenic genes and the enhanced biosynthesis of carotenoids in C.
      zofingiensis. 

PMID- 27034041
TI  - AGROBACTERIUM-MEDIATED TRANSFORMATION IN THE GREEN ALGA HAEMATOCOCCUS PLUVIALIS
      (CHLOROPHYCEAE, VOLVOCALES)(1).
AB  - The first successful Agrobacterium-mediated transformation of the green alga
      Haematococcus pluvialis Flot. using the binary vectors hosting the genes coding
      for GUS (beta-glucuronidase), GFP (green fluorescent protein), and hpt
      (hygromycin phosphotransferase) is reported here. Colonies resistant to
      hygromycin at 10 mg . L(-1) expressed beta-glucuronidase. The greenish yellow
      fluorescence of GFP was observed when the hygromycin-resistant cells were viewed
      with a fluorescent microscope. PCR was used to successfully amplify fragments of
      the hpt (407 bp) and GUS (515 bp) genes from transformed cells, while Southern
      blots indicated the integration of the hygromycin gene into the genome of H.
      pluvialis. SEM indicated that the cell wall of H. pluvialis was altered on
      infection with Agrobacterium. The transformation achieved here by Agrobacterium
      does not need treatment with acetosyringone or the wounding of cells. A robust
      transformation method for this alga would pave the way for manipulation of many
      important pathways relevant to the food, pharmaceutical, and nutraceutical
      industries. 

PMID- 27034042
TI  - MOLECULAR CHARACTERIZATION AND ANTIBODY DETECTION OF A NITROGEN-REGULATED CELL
      SURFACE PROTEIN OF THE COCCOLITHOPHORE EMILIANIA HUXLEYI (PRYMNESIOPHYCEAE)(1).
AB  - Dissolved organic nitrogen (DON) can account for a significant portion of total
      nitrogen in some aquatic environments, and many species of phytoplankton are able
      to scavenge nitrogen from this pool especially when inorganic nitrogen is
      limiting. Emiliania huxleyi (Lohmann) H. W. Hay et H. Mohler is able to use
      various forms of DON for growth, including several amino acids, purines, and
      pyrimidines. A cell-surface protein up-regulated in the absence of inorganic
      nitrogen, NRP1, is hypothesized to play a role in the metabolism of one or more
      of these organic nitrogen forms. Here, the genomic and cDNA sequence of NRP1 is
      reported. Structural predictions based on the amino acid sequence suggest a
      pyridoxal-5'-phosphate-dependent enzyme that may have a role in acquiring
      nitrogen from amino acids. Further evidence for the function of NRP1 is measured
      in spent media from nitrogen-limited cultures, which contain NRP1 and have
      glutaminase and formamidase activity. Field studies using an antibody to NRP1
      show that it is expressed in E. huxleyi during bloom conditions in a Norwegian
      fjord. 

PMID- 27034043
TI  - GLYCOCONJUGATE ORGANIZATION OF ENTEROMORPHA (=ULVA) FLEXUOSA AND ULVA FASCIATA
      (CHLOROPHYTA) ZOOSPORES(1).
AB  - Ecologically successful algae that colonize natural and artificial substrates in
      the marine environment have distinct strategies for opportunistic dispersal and
      settlement. The objective of this research was to visualize molecular
      architecture of zoospores from Enteromorpha (=Ulva) flexuosa (Wulfen) J. Agardh
      and Ulva fasciata Delile that coexist but alternate in dominance on an intertidal
      bench. Multiple fluorescent lectins were used to stabilize and probe for diverse
      zoospore glycoconjugates (GC) that could be involved in cell and substrate
      interactions. Results from epifluorescence microscopy showed distinct cellular
      and extracellular polymeric substance (EPS) domains of GC relative to settlement
      morphologies. Glycoconjugates were similar for both species with (1) alpha-d
      mannose and/or glucose moieties localized on flagella, the anterior domes and
      anterior regions, the plasma membranes, and EPS; (2) alpha-fucose localized on
      flagella and anterior regions; (3) N or alpha,beta-N acetylglucosamine localized
      on flagella, the anterior regions, and EPS; and (4) varied N-acetylgalactosamine
      and/or galactose moieties localized on each domain for both species excluding the
      plasma membranes. Some differences in lectin binding were observed for each
      species at the flagella, the anterior domes, and the plasma membranes.
      Glycoconjugate distributions shifted with morphological changes that followed
      initial adhesion. TEM of E. flexuosa zoospore stages following carbohydrate
      stabilizing fixations and gold-conjugated lectin probes resolved GC with alpha-d
      mannose and/or glucose, and/or N-acetylglucosamine at the plasma membrane, ER and
      diverse vesicles of the anterior pole, EPS, and discontinuous regions or knobs
      associated with flagellar surfaces. The distinct distribution and diversity of
      zoospore GC may be central to recognition and attachment on diverse substrata by
      these algae. 

PMID- 27034044
TI  - CHARACTERIZATION OF MARTENSIA (DELESSERIACEAE, RHODOPHYTA) BASED ON A
      MORPHOLOGICAL AND MOLECULAR STUDY OF THE TYPE SPECIES, M. ELEGANS, AND M.
      NATALENSIS SP. NOV. FROM SOUTH AFRICA(1).
AB  - An examination of a series of collections from the coast of Natal, South Africa,
      has revealed the presence of two species of Martensia C. Hering nom. cons: M.
      elegans C. Hering 1841, the type species, and an undescribed species, M.
      natalensis sp. nov. The two are similar in gross morphology, with both having the
      network arranged in a single band, and with reproductive thalli of M. elegans
      usually larger and more robust than those of M. natalensis. Molecular studies
      based on rbcL sequence analyses place the two in separate, strongly supported
      clades. The first assemblage occurs primarily in the Indo-West Pacific Ocean, and
      the second is widely distributed in tropical and warm-temperate waters. Criteria
      that have been used in the past for separating the two, namely, the number and
      shape of the blades, the presence of a single- versus a multiple-banded network,
      and blade margins entire or toothed, were determined to be unreliable. Although
      the examination of additional species is required, the morphology and position of
      procarps and cystocarps, whether at or near the corners of the longitudinal
      lamellae and the cross-connecting strands or along the lobed, membranous edges of
      the longitudinal lamellae or on the thallus margins, may prove to be diagnostic
      at the subgenus level. We recognize subg. Martensia, including the type of
      Martensia: M. elegans and subg. Mesotrema (J. Agardh) De Toni based on Martensia
      pavonia (J. Agardh) J. Agardh. 

PMID- 27034045
TI  - IDENTIFICATION AND TOXICITY OF ALEXANDRIUM TAMARENSE (DINOPHYCEAE) IN SCOTTISH
      WATERS(1).
AB  - Contamination of shellfish with paralytic shellfish poisoning (PSP) toxins
      produced by Alexandrium species poses a potential threat to the sustainability of
      the Scottish aquaculture industry. Routine LM analysis of water samples from
      around the Scottish coast has previously identified Alexandrium (Dinophyceae) as
      a regular part of the spring and summer phytoplankton communities in Scottish
      coastal waters. In this study, Alexandrium tamarense (M. Lebour) Balech isolated
      from sediment and water samples was established in laboratory culture. Species
      identification of these isolates was confirmed using thecal plate dissections and
      by molecular characterization based on their LSU and, in some cases, ITS rDNA
      sequence. Molecular characterization and phylogenetic analysis showed the
      presence of two ribotypes of A. tamarense: Group I (North American ribotype) and
      Group III (Western European ribotype). Assessment of PSP toxin production using
      hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC
      MS/MS) showed that A. tamarense Group I produced a complex array of toxins
      (~2,000 fg STX equivalents . cell(-1) ) with the major toxins being C2,
      neosaxitoxin (NEO), saxitoxin (STX), gonyautoxin-4 (GTX-4), and GTX-3, while A.
      tamarense Group III did not produce toxins. Historically, it was considered that
      all Alexandrium species occurring in Scottish waters produce potent PSP toxins.
      This study has highlighted the presence of both PSP toxin-producing and benign
      species of A. tamarense and questions the ecological significance of this
      finding. 

PMID- 27034046
TI  - SYSTEMATICS OF THE BATRACHOSPERMALES (RHODOPHYTA)-A SYNTHESIS(1).
AB  - Recent molecular and morphological data necessitate a major taxonomic revision of
      the Batrachospermales, an order of red algae, distributed in freshwater habitats
      throughout the world. This article is a synthesis of available information with
      some targeted additional sequence data, resulting in a few relatively
      conservative taxonomic changes to begin the process of creating a natural
      taxonomy for the Batrachospermales. To increase the information content of our
      taxonomic categories, and in particular to reduce paraphyly, we describe one new
      genus (Kumanoa) and a new section in Batrachospermum (section Macrospora), and we
      amend the circumscriptions of the family Batrachospermaceae (to include
      Lemaneaceae and Psilosiphonaceae), the genus Batrachospermum (to exclude the
      sections Contorta and Hybrida, raised to genus level as Kumanoa), and the
      sections Aristata, Helminthoidea, and Batrachospermum of Batrachospermum. We also
      provide a new name, B. montagnei, for the illegitimate B. guyanense, and
      recognize an informal paraphyletic grouping of taxa within Batrachospermum, the
      "Australasica Group." This taxonomic synthesis increases the level of monophyly
      within the Batrachospermales but minimizes taxonomic change where data are still
      inadequate. 

PMID- 27034047
TI  - GEITLERINEMA SPECIES (OSCILLATORIALES, CYANOBACTERIA) REVEALED BY CELLULAR
      MORPHOLOGY, ULTRASTRUCTURE, AND DNA SEQUENCING(1).
AB  - Geitlerinema amphibium (C. Agardh ex Gomont) Anagn. and G. unigranulatum (Rama N.
      Singh) Komarek et M. T. P. Azevedo are morphologically close species with
      characteristics frequently overlapping. Ten strains of Geitlerinema (six of G.
      amphibium and four of G. unigranulatum) were analyzed by DNA sequencing and
      transmission electronic and optical microscopy. Among the investigated strains,
      the two species were not separated with respect to cellular dimensions, and
      cellular width was the most varying characteristic. The number and localization
      of granules, as well as other ultrastructural characteristics, did not provide a
      means to discriminate between the two species. The two species were not separated
      either by geography or environment. These results were further corroborated by
      the analysis of the cpcB-cpcA intergenic spacer (PC-IGS) sequences. Given the
      fact that morphology is very uniform, plus the coexistence of these populations
      in the same habitat, it would be nearly impossible to distinguish between them in
      nature. On the other hand, two of the analyzed strains were distinct from all
      others based on the PC-IGS sequences, in spite of their morphological similarity.
      PC-IGS sequences indicate that these two strains could be a different species of
      Geitlerinema. Using morphology, cell ultrastructure, and PC-IGS sequences, it is
      not possible to distinguish G. amphibium and G. unigranulatum. Therefore, they
      should be treated as one species, G. unigranulatum as a synonym of G. amphibium. 

PMID- 27034048
TI  - PHYLOGENETIC ANALYSIS OF PSEUDOCHLORODESMIS STRAINS REVEALS CRYPTIC DIVERSITY
      ABOVE THE FAMILY LEVEL IN THE SIPHONOUS GREEN ALGAE (BRYOPSIDALES,
      CHLOROPHYTA)(1).
AB  - The genus Pseudochlorodesmis (Bryopsidales) is composed of diminutive siphons of
      extreme morphological simplicity. The discovery of Pseudochlorodesmis-like
      juveniles in more complex Bryopsidales (e.g., the Halimeda microthallus stage)
      jeopardized the recognition of this genus. Confronted with this uncertainty,
      taxonomists transferred many simple siphons into a new genus, Siphonogramen. In
      this study, we used a multimarker approach to clarify the phylogenetic and
      taxonomic affinities of the Pseudochlorodesmis-Siphonogramen (PS) complex within
      the more morphologically complex bryopsidalean taxa. Our analyses reveal a new
      layer of diversity largely distinct from the lineages containing the structurally
      complex genera. The PS complex shows profound cryptic diversity exceeding the
      family level. We discuss a potential link between thallus complexity and the
      prevalence and profundity of cryptic diversity. For taxonomic simplicity and as a
      first step toward clarifying the taxonomy of these simple siphons, we propose to
      maintain Pseudochlorodesmis as a form genus and subsume Siphonogramen and
      Botryodesmis therein. 

PMID- 27034049
TI  - MICROFISSURATA GEN. NOV. (BACILLARIOPHYTA), A NEW DIATOM GENUS FROM DYSTROPHIC
      AND INTERMITTENTLY WET TERRESTRIAL HABITATS(1).
AB  - A new freshwater benthic diatom genus, Microfissurata gen. nov., was identified
      from light and scanning electron micrographs. The most characteristic
      morphological feature (referred to also by the name of the new genus) is the
      structure of the striae/alveoli, which are simple, mostly uninterrupted,
      transapical slits. The combination of characteristics of the new genus is unique.
      It includes two new species: Microfissurata paludosa Cantonati et Lange-Bert. sp.
      nov. and M. australis Van de Vijver et Lange-Bert. sp. nov., distributed in
      Europe and on an austral island, respectively. The new genus occurs in freshwater
      dystrophic lakes, pools, seepage springs, mires, and in intermittently wet
      terrestrial habitats. It is not abundant but widespread wherever these habitat
      types are well developed, in Nordic-alpine and sub-Antarctic areas. Overall, the
      new genus appears to be mostly epiphytic (bryophilous) and capable of tolerating
      a wide range of moisture conditions (xerotolerant). The finding of the type
      species (M. paludosa) in a well-investigated area like central Europe highlights
      the diatom species richness of dystrophic habitats and their importance for
      diatom biodiversity conservation. 

PMID- 27034050
TI  - NITZSCHIA ALICAE SP. NOV. AND N. PURIFORMIS SP. NOV., NEW DIATOMS FROM EUROPEAN
      RIVERS AND COMPARISON WITH THE TYPE MATERIAL OF N. SUBLINEARIS AND N. PURA(1).
AB  - Nitzschia sublinearis Hustedt and N. pura Hustedt are common oligosaprobic
      freshwater diatom species that frequently occur in diatom inventories, thus being
      important in water quality studies. Both are considered as species with
      overlapping diagnostic criteria in several floras, which is typical of the whole
      genus Nitzschia. The type material of Hustedt of N. sublinearis and N. pura was
      examined using LM and EM in order to document the range of variation within the
      type populations and to compare it with populations occurring in different
      European rivers. Detailed observations allowed recognition of two new freshwater
      diatom species: N. alicae sp. nov., occurring in mesotrophic up to eutrophic
      conditions, and N. puriformis sp. nov., mostly occurring in oligotrophic
      habitats, both in rivers and streams at middle and high altitudes. The most
      reliable taxonomic features that separate both new species from the most similar
      taxa are the density of fibulae and striae, valve shape, and valve width as well
      as the shape of areolae. Morphological examination of different populations
      indicates that N. puriformis is relatively common in European rivers and has been
      overlooked to date and confounded with N. pura by several researchers. By
      contrast, N. alicae has, to date, been collected only in Slovakia and Northern
      Italy, but with a high frequency of occurrence and sometimes in high abundance at
      sites. 

PMID- 27034051
TI  - SHORT-TERM MEASUREMENT OF CARBON STABLE ISOTOPE DISCRIMINATION IN PHOTOSYNTHESIS
      AND RESPIRATION BY AQUATIC MACROPHYTES, WITH MARINE MACROALGAL EXAMPLES(1).
AB  - Progress in the study of stable isotope discrimination in carbon assimilation by
      aquatic macrophytes has been slower than for other groups of primary producers,
      such as phytoplankton and terrestrial plants. A probable reason has been the
      methodologies employed for such a study: field collections or long-term
      incubations, both relying on the observation of changes in carbon isotope
      composition of plant tissue. Here, we present a short-term incubation method
      based on the change in carbon stable isotope composition in water. Its
      fundamental advantage over the other approaches is that the change in stable
      isotope composition in water in a closed system is much faster than in the plant
      tissue. We applied the method to investigate the relationship between carbon
      assimilation intensity and isotope discrimination. The results included a
      relatively small discrimination in respiration, a significant influence of carbon
      assimilation rate on discrimination, and the suggestion of HCO3 (-) or CO2 uptake
      in photosynthesis. The information gathered using this method would be difficult
      to obtain in other ways, and so we believe that it should contribute to a better
      understanding of the physiology and ecology of aquatic macrophytes. 

PMID- 27034053
TI  - GENETIC AND MORPHOLOGICAL ANALYSES OF THE SOUTHERN BULL KELP DURVILLAEA
      ANTARCTICA (PHAEOPHYCEAE: DURVILLAEALES) IN NEW ZEALAND REVEAL CRYPTIC SPECIES
      (VOL 45:436-43).

PMID- 27034052
TI  - DEVELOPMENT OF IMMUNOASSAYS FOR THE IRON-REGULATED PROTEINS FERREDOXIN AND
      FLAVODOXIN IN POLAR MICROALGAE(1).
AB  - While the growth of Southern Ocean phytoplankton is often limited by iron
      availability, there are no comparable experiments on sea-ice algae. Here we
      assess the use of ferredoxin and flavodoxin to investigate the iron nutritional
      status of sea-ice algae and describe the development of a quantitative
      immunoassay for both proteins in marine diatoms. High-affinity monoclonal
      antibodies toward both proteins were produced from Cylindrotheca closterium
      (Ehrenb.) J. M. Lewin et Reimann, and these were used to develop Western blots.
      Western blots run on whole protein extracts detected both proteins with little
      cross-reactivity toward other proteins. The two proteins could be successfully
      quantitated when applied to gels at between 5 and 50 ng in a volume of 25 MUL
      (0.2-2 MUg . mL(-1) ). Flavodoxin and ferrodoxin expression was examined in the
      Antarctic diatoms Entomoneis kjellmannii (Cleve) Poulin et Cardinal, Navicula
      directa (W. Sm.) Ralfs, Fragilariopsis curta (Van Heurck) Hust., Pseudo-nitzschia
      sp., Porosira glacialis (Grunow) E. G. Jorg., Fragilariopsis cylindrus (Grunow)
      Willi Krieg., Fragilariopsis sublinearis (Van Heurck) Heiden et Kolbe, C.
      closterium, Nitzschia lecointei Van Heurck, and the dinoflagellate Polarella
      glacialis Montresor, Procaccini et Stoecker. Two Arctic isolates were also
      examined, Nitzschia frigida (Grunow) and Fragilariopsis oceanica (Cleve) Hasle.
      Significant heterogeneity of protein expression was observed despite all cultures
      being grown in iron-replete f/2 medium. Only one species, F. cylindrus, displayed
      the expected expression of ferredoxin only in iron-replete medium. Four were
      observed to produce both proteins under iron-replete conditions. Ferredoxin was
      not detected at all in F. curta and Pseudo-nitzschia sp., but distinct flavodoxin
      bands were observed in both of these organisms. All species examined were
      observed to express either flavodoxin or ferredoxin or both of the proteins as
      determined by Western immunoblotting. 

PMID- 27034054
TI  - Association of neurotrophins, inflammation and stress with suicide risk in young
      adults.
AB  - BACKGROUND: Stress, anxiety and various neurobiological changes have been
      postulated to be associated with increased suicidal ideation. Hence, this study
      was undertaken to evaluate the serum concentrations of neurotrophins,
      inflammatory markers and stress concentrations as predictors of suicidal risk
      among young adults. METHODS: This cross-sectional study was conducted in a
      tertiary care referral center in South India from March 2014 to February 2015. We
      recruited 42 suicide attempters and 42 age- and gender-matched healthy controls.
      The serum concentrations of neurotrophins (BDNF and NT-3), inflammatory markers
      (hs-CRP and IL-6) were assessed. Stress severity was assessed by Presumptive
      Stressful Life Events scale (PSLE) and Daily Hassles and Uplifts Scale-revised
      (DHUS-R). Psychological distress and Suicide risk was assessed using Hospital
      Anxiety and Depression Scale (HADS) and Mini International Neuropsychiatric
      Interview (MINI) respectively. RESULTS: Suicide attempters tend to show
      significantly lower concentrations of neurotrophins and significantly higher
      concentrations of inflammatory markers. We observed significant negative
      correlation of neurotrophins with inflammatory markers, stress, and suicide risk.
      In multivariate linear regression model, hs-CRP [adjusted beta=0.333, p<0.0001],
      PSLE [adjusted beta=0.133, p=0.029], DHUS-R [adjusted beta=0.159, p=0.018]
      emerged as independent predictors of suicide risk (R(2)=0.76). CONCLUSION: Our
      results suggest that inflammation and stress scores have a moderate association
      with suicidal ideation.

PMID- 27034055
TI  - Neutrophil left shift and white blood cell count as markers of bacterial
      infection.
AB  - Neutrophil left shift and white blood cell (WBC) count are routine laboratory
      tests used to assess neutrophil state, which depends on supply from the bone
      marrow and consumption in the tissues. If WBC count is constant, the presence of
      left shift indicates an increase of neutrophil consumption that is equal to an
      increase of production. A decrease in WBC count indicates that neutrophil
      consumption surpasses supply. During a bacterial infection, large numbers of
      neutrophils are consumed. Thus, from onset of infection to recovery, dynamic
      changes occur in WBC count and left shift data, reflecting the mild to serious
      condition of the bacterial infection. Although various stimuli in healthy and
      pathological conditions also cause left shift, a change as sudden and significant
      is only seen in bacterial infection. Left shift does not occur in the extremely
      early or late phases of infection; therefore, assessing data from a single time
      point is unsuitable for diagnosing a bacterial infection. We argue that time
      series data of left shift and WBC count reflect real-time neutrophil consumption
      during the course of a bacterial infection, allowing more accurate evaluation of
      patient condition. 

PMID- 27034056
TI  - Geographic distribution of human Blastocystis subtypes in South America.
AB  - Blastocystis is a cosmopolitan enteric protist colonizing probably more than 1
      billion people. This protozoan exhibits genetic diversity and is subdivided into
      subtypes (STs). The aim of this study was to determine the distribution of
      Blastocystis STs in symptomatic and asymptomatic human samples from different
      countries of South America. A total of 346 fecal samples were genotyped by SSU
      rDNA showing ST1 (28.3%), ST2 (22.2%), ST3 (36.7%), ST4 (2%), ST5 (2.3%), ST6
      (2%), ST7 (2.3%), ST8 (0.6%), ST12 (0.9%) and a novel ST (2.7%). These findings
      update the epidemiology of Blastocystis in South America and expand our knowledge
      of the phylogeographic differences exhibited by this stramenopile.

PMID- 27034057
TI  - The burden of cutaneous melanoma and status of preventive measures in Central and
      South America.
AB  - RATIONALE AND OBJECTIVE: Very little is known about the burden of cutaneous
      melanoma in Central and South America, despite the existence of a reasonable
      amount of population-based data. We present data on melanoma incidence calculated
      in a standardized way for Central and South America, as well as an overview of
      primary and secondary prevention issues in the region. METHODS: Cancer registry
      data on all incident cases reported in the different registries present in
      Central and South America were combined to provide registry-based country
      estimates of age-standardized, sex-specific cutaneous melanoma incidence overall,
      and by histological subtype and anatomical site. A literature search provided
      additional information. RESULTS: Age-standardized incidence rates were between 1
      and 5 per 100,000 and tended to be higher further away from the equator.
      Cutaneous melanomas of the acral type, mostly occurring on the lower limbs, are a
      distinguishing feature of melanoma in Central and South America in comparison
      with high-incidence areas. Several preventive measures, both primary and
      secondary, are in place, albeit largely without evaluation. CONCLUSION: Due to
      incomplete registration and different registration practices, reliable and
      comparable data on melanoma were difficult to obtain; thus it is likely that the
      true burden of melanoma in Central and South America has been underestimated. The
      different characteristics of the cutaneous melanoma patient population in terms
      of anatomical site and histological type distribution imply a need for adapted
      primary and secondary prevention measures. The generally high ambient ultraviolet
      radiation levels require sufficient sun protection measures.

PMID- 27034058
TI  - Mild protein hydrolysation of lactose-free milk further reduces milk-related
      gastrointestinal symptoms.
AB  - Gastrointestinal symptoms associated with milk are common. Besides lactose, milk
      proteins may cause symptoms in sensitive individuals. We have developed a method
      for mild enzymatic hydrolysation of milk proteins and studied the effects of
      hydrolysed milk on gastrointestinal symptoms in adults with a self-diagnosed
      sensitive stomach. In a double blind, randomised placebo-controlled study, 97
      subjects consumed protein-hydrolysed lactose-free milk or commercially available
      lactose-free milk for 10 d. Frequency of gastrointestinal symptoms during the
      study period was reported and a symptom score was calculated. Rumbling and
      flatulence decreased significantly in the hydrolysed milk group (P < 0.05). Also,
      the total symptom score was lower in subjects who consumed hydrolysed milk (P <
      0.05). No difference between groups was seen in abdominal pain (P = 0.47) or
      bloating (P = 0.076). The results suggest that mild enzymatic protein
      hydrolysation may decrease gastrointestinal symptoms in adults with a sensitive
      stomach. 

PMID- 27034059
TI  - Learning process and improvement of point-of-care ultrasound technique for
      subxiphoid visualization of the inferior vena cava.
AB  - BACKGROUND: Medical residents' training in ultrasonography usually follows the
      recommendations of the American College of Emergency Physicians (ACEP), even
      though these do not provide specific technical guidelines. Adequate training is
      considered to require 25 practical iterations in the majority of ultrasound
      procedures. However, the effectiveness of this approach has not been verified
      experimentally. We set out to determine the number of repetitions required for an
      acceptable ultrasound procedure of the inferior vena cava (IVC), as an important
      and emerging ultrasound procedure in cardiology. METHODS: Using three human
      models, each of eight medical residents in the Emergency Medicine (EM) Program at
      the Universidad del Rosario performed 25 iterations of the recommended procedure,
      with image quality evaluation by an EM physician expert in the technique.
      Logistic regression analysis was used to determine the lowest number of
      repetitions required to achieve an adjusted probability of success of 80 and 90
      %, respectively. RESULTS: We obtained 200 ultrasound images. The percentage
      success by each resident ranged from 52 to 96 %. There was no statistical
      significance in the relation between gender and success (p = 0.83), but there was
      an association between year of residency and success (p < 0.001). The average
      time taken for each procedure was 17.3 s (SD 8.1); there was no association
      between the time taken and either repetition number or image quality. We
      demonstrate that eleven repetitions are required to achieve acceptable image
      quality in 80 %, and that 21 repetitions are required to achieve acceptable image
      quality in 90 %. CONCLUSIONS: This is the first study to formally evaluate the
      effectiveness of recommended training in ultrasound techniques. Our findings
      demonstrate that training comprising 25 procedural repetitions is easily
      sufficient to achieve optimal image quality, and they also provide empiric
      knowledge toward elucidating the times and minimum repetitions needed to acquire
      and improve ultrasonographic technique in novice operators to a level which
      fulfills quality requirements for interpretation.

PMID- 27034060
TI  - Laparoscopic Sleeve Gastrectomy in the Postpartum Period: Increased Risk of
      Bleeding, a Challenging Situation.
AB  - The female population represents three-fourths of patients undergoing a bariatric
      procedure and could be scheduled for surgery in their postpartum period. We
      report a difficult case of a female patient who underwent a laparoscopic sleeve
      gastrectomy 6 weeks postpartum. The postpartum period is accompanied by
      pronounced vasodilatation with transient portal hypertension. Most of the
      hemodynamic alterations occurring during pregnancy return to baseline within 6-8
      weeks after delivery. Bariatric surgery in the postpartum period should be
      avoided in order for the cardiovascular system to regain its normality.

PMID- 27034061
TI  - An Exploration of System-Level Factors and the Geographic Variation in Bariatric
      Surgery Utilization.
AB  - There is wide geographic variation in bariatric surgery rates, although higher
      regional rates of obesity are not correlated with higher rates of surgery. In
      this study, four system-level factors were explored as contributors to this
      geographic variation. Geographic utilization rates of bariatric surgery showed no
      correlation to the number of bariatric surgeons, number of accredited centers,
      and the percentage of patients with a recent primary care visit. The total number
      of surgical discharges was weakly correlated with bariatric surgery rates (r =
      0.26, p = <0.001). As surgeon supply, accredited bariatric centers, overall
      surgical volume, and access to primary care do not appear to heavily influence
      bariatric surgery rates, future studies are needed to identify additional factors
      that may explain the underutilization of bariatric surgery.

PMID- 27034062
TI  - Copper Deficiency after Gastric Bypass for Morbid Obesity: a Systematic Review.
AB  - A large number of patients undergoing bariatric surgery are deficient in copper,
      and Roux-en-Y gastric bypass can further aggravate it. Delays in diagnosis and
      treatment of copper deficiency can leave patients with residual neurological
      disability. This has led to recommendation from the British Obesity and Metabolic
      Surgery Society that copper levels should be monitored annually after gastric
      bypass. This review concludes that copper deficiency in adequately supplemented
      patients is rare and can be adequately treated if a related haematological or
      neurological disorder is diagnosed. The cost of routine monitoring may therefore
      not be justified for adequately supplemented, asymptomatic patients who have
      undergone Roux-en-Y gastric bypass. The screening may however be necessary for
      high-risk patient groups to prevent severe complications and permanent
      disability.

PMID- 27034063
TI  - A Fluorescence Immunochromatographic Assay Using Europium (III) Chelate
      Microparticles for Rapid, Quantitative and Sensitive Detection of Creatine Kinase
      MB.
AB  - The isoenzyme creatine kinase MB is very important for diagnosis of acute
      myocardial infarction (AMI). Some CK-MB immunoassays are sensitive, accurate and
      available for clinical application, but they are expensive and time-consuming
      procedures. Furthermore, conventional fluorescence immunochromatographic assays
      (FL-ICAs) have suffered from background fluorescence interference and low
      analytical sensitivity. A rapid and simple FL-ICA with Eu (III) chelate
      polystyrene microparticles was developed to determine CK-MB in 50uL serum samples
      using a portable test strip reader by measuring the fluorescence peak heights of
      the test line (HT) and the control line (HC) in 12 min. The assay was reliable
      with a good correlation coefficient between HT/HC ratio and CK-MB concentration
      in samples. A linear range was 0.85-100.29 ng/mL for CK-MB, and the LOD was 0.029
      ng/mL. The intra- and inter-assay coefficients of variation (CV) were both <10 %
      and the average recoveries were from 90.17 % -112.63 % for CK-MB. The system
      performed well in interference experiments. Furthermore, a highly significant
      correlation (r = 0.9794, P < 0.001) between this method and the commercially
      available bioMerieux mini VIDAS system were attained for measuring 120 CK-MB
      samples. These results indicated that the Eu (III) chelate microparticles-based
      FL-ICA is simple, fast, highly sensitive, reliable, and reproducible for point-of
      care testing of CK-MB concentrations in serum. Graphical Abstract ?. 

PMID- 27034064
TI  - A Reversible Pyrene-based Turn-on Luminescent Chemosensor for Selective Detection
      of Fe(3+) in Aqueous Environment with Logic Gate Application.
AB  - A new Schiff-base, HL luminescent chemosensor of 1-amino pyrene and 8-hydroxy
      quinoline-2-carboxaldehyde was synthesized which demonstrates selective
      fluorimetric detection of Fe(3+) in aqueous medium with detection limit of 2.52 *
      10(-8) M. The receptor shows selective 'turn-on' response towards Fe(3+) over
      other metal ions. This gradual 'turn-on' fluorescence response for Fe(3+) may be
      induced via CHEF (chelation-enhanced fluorescence) through close proximity of
      pyrene rings. The stoichiometry and binding property of HL with Fe(3+) was
      examined by emission studies. In presence of Fe(3+), HL also exhibits reversible
      change in emission pattern with EDTA and thus offers an interesting property of
      molecular 'INHIBIT' logic gate with Fe(3+) and EDTA as chemical inputs. 

PMID- 27034065
TI  - Effect of light intensity and various organic acids on the growth of Rhodobacter
      sphaeroides LHII-deficient mutant in a turbidostat culture.
AB  - The composition of photosynthetic apparatus of Rhodobacter sphaeroides wild
      strain 2.4.1 and its LHII-deficient mutant DBCOmega was compared. The absence of
      LHII in the mutant was confirmed by comparison of chromatophores spectra and by
      the absence of electrophoretic band corresponding to LHII complex. Continuous
      turbidostat cultures of wild strain and its LHII-deficient mutant were compared
      in response to different light intensities. Cultures were grown using lactate,
      mixture of lactate and acetate or succinate as carbon source. For comparative
      analysis, an approximation of experimental data by Monod and Gompertz equations
      were used. Cultures of DBCOmega had lower growth rates than wild strain when
      grown on lactate as electron donor and carbon source. Cultures of both strains
      grown on lactate and acetate or on succinate had similar growth rates. The
      cultures showed maximum growth rates when grown with succinate.
      Bacteriochlorophyll a content increased in both strains with decrease of incident
      light intensity. However, the variation of Bchl a content in wild strain was much
      more significant. Under light-limiting conditions, bacteriochlorophyll a content
      in DBCOmega was 4-5 times lower than in the wild strain. Under light-saturating
      conditions, it was only 1.5-2.5 times lower. Growing with lactate or with lactate
      and acetate, the mutant switched from light limitation under low light
      intensities to limitation by organic acids under higher light, whereas the
      parental strain had similar switch of limiting factor only when growing with
      lactate and acetate mixture. DBCOmega mutant has higher minimal light intensity
      enabling growth on any organic acid as a substrate. When growing with lactate or
      with lactate and acetate, the mutant reached maximum growth rate at lower light
      intensities than the wild strain. This phenomenon was observed for the first
      time. Taking into account the concentration of BChl a under light-limiting
      conditions, the thickness of the suspension capable of effective light absorption
      could be increased by 4-5 times, which is favorable for intensive cultivation.

PMID- 27034066
TI  - Effects of exogenous beta-carotene, a chemical scavenger of singlet oxygen, on
      the millisecond rise of chlorophyll a fluorescence of cyanobacterium
      Synechococcus sp. PCC 7942.
AB  - Singlet-excited oxygen (1O 2* ) has been recognized as the most destructive
      member of the reactive oxygen species (ROS) which are formed during oxygenic
      photosynthesis by plants, algae, and cyanobacteria. ROS and 1O 2* are known to
      damage protein and phospholipid structures and to impair photosynthetic electron
      transport and de novo protein synthesis. Partial protection is afforded to
      photosynthetic organism by the beta-carotene (beta-Car) molecules which accompany
      chlorophyll (Chl) a in the pigment-protein complexes of Photosystem II (PS II).
      In this paper, we studied the effects of exogenously added beta-Car on the
      initial kinetic rise of Chl a fluorescence (10-1000 MUs, the OJ segment) from the
      unicellular cyanobacterium Synechococcus sp. PCC7942. We show that the added beta
      Car enhances Chl a fluorescence when it is excited at an intensity of 3000 MUmol
      photons m-2 s-1 but not when excited at 1000 MUmol photons m-2 s-1. Since beta
      Car is an efficient scavenger of 1O 2* , as well as a quencher of 3Chl a *
      (precursor of 1O 2* ), both of which are more abundant at higher excitations, we
      assume that the higher Chl a fluorescence in its presence signifies a protective
      effect against photo-oxidative damages of Chl proteins. The protective effect of
      added beta-Car is not observed in O2-depleted cell suspensions. Lastly, in
      contrast to beta-Car, a water-insoluble molecule, a water-soluble scavenger of 1O
      2* , histidine, provides no protection to Chl proteins during the same time
      period (10-1000 MUs).

PMID- 27034067
TI  - Mitochondrial Dysfunction in Schizophrenia: Determination of Mitochondrial
      Respiratory Activity in a Two-Hit Mouse Model.
AB  - Schizophrenia is a chronic mental illness in which mitochondrial dysfunction has
      been suggested. Our laboratory recently developed a juvenile murine two-hit model
      (THM) of schizophrenia based on the combination of gestational inflammation,
      followed by juvenile restraint stress. We previously reported that relevant
      behaviors and neurochemical disturbances, including oxidative stress, were
      reversed by the antioxidant lipoic acid (LA), thereby pointing to the central
      role played by oxidative abnormalities and prompting us to investigate
      mitochondrial function. Mitochondrial activity was determined with the
      MitoXpress(r) commercial kit in two schizophrenia-relevant regions (prefrontal
      cortex (PFC) and striatum). Measurements were performed in state 3, with
      substrates for complex I- and complex II-induced respiratory activity (IRA). We
      observed an increase in complex I IRA in the PFC and striatum in both sexes but
      an increase in complex II activity only in males. LA treatment prevented this
      increase only in complex II IRA in males. Expression levels of the different
      respiratory chain complexes, as well as fission/fusion proteins and protein
      carbonylation, were unchanged. In conclusion, our juvenile schizophrenia THM
      shows an increase in mitochondrial activity reversed by LA, specifically in
      complex II IRA in males. Further investigations are required to determine the
      mechanisms of these modifications. 

PMID- 27034068
TI  - Expression Profile of Long Non-Coding RNAs in Serum of Patients with Multiple
      Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the
      central nervous system (CNS) that leads to severe neurological disability. There
      is an interest in potential biomarkers that could provide information predicting
      disease activity and progression. Long non-coding RNAs (lncRNAs) have been
      reported to be involved in the pathogenesis of various human disorders, such as
      oncologic, cardiovascular, and neurodegenerative diseases. No studies have so far
      explored a potential link between lncRNAs and MS pathology. We screened 84
      lncRNAs, involved in autoimmunity and human inflammatory response, in the serum
      of relapsing-remitting MS (RR-MS) patients (n = 12), age-matched controls (n =
      12), and in patients with idiopathic inflammatory myopathy (IIM) (n = 12). We
      used the following criteria for lncRNAs analysis: fold change >2 and p < 0.05.
      According to these criteria, by real-time PCR, we identified three lncRNAs up
      regulated in RR-MS patients respectively to controls: nuclear paraspeckle
      assembly transcript 1 (NEAT1), taurine up-regulated 1 (TUG1), and 7SK small
      nuclear (RN7SK RNA). Literature data showed that NEAT1, TUG1, and RN7SK RNA play
      an important role in neurodegenerative processes. Our results indicate that these
      lncRNAs may be involved in MS pathogenesis. Additional experimental data are
      needed to clarify the molecular mechanisms through which lncRNAs up-regulation
      may have a role in MS. 

PMID- 27034069
TI  - Effects of protein leakage on online monitoring of ultraviolet absorbance in
      spent dialysate.
AB  - Recently, dialysis dose during hemodialysis treatment has been monitored by
      measuring the concentration of urea-like solutes such as uric acid in spent
      dialysate using near-ultraviolet (UV) light. The measured absorbance has been
      shown to have a good correlation with the time course of urea level even if the
      absorbance does not result from urea. However, the spent dialysate includes
      various solutes such as uric acid and albumin as well as unknown solutes that
      also absorb UV light. The effects of these solutes on monitored absorbance values
      are not clear. In this study, we evaluated the effect of protein leakage on data
      from the UV monitoring of spent dialysate. Albumin leakage in the earlier stage
      of the treatment may result in an increase in absorbance greater than the
      expected value. As a result, there is a possibility that the dialysis dose is
      overestimated. On the other hand, the quantity of albumin leakage could be
      estimated by a spent dialysate monitoring technique combined with a protein
      removal process. 

PMID- 27034071
TI  - Morphometric and chronological behavior of 2.45 GHz microwave ablation zones for
      colorectal cancer metastases and hepatocellular carcinoma in the liver:
      preliminary report.
AB  - BACKGROUND: Percutaneous microwave ablation (MWA) is increasingly utilized in the
      treatment of primary and secondary hepatic malignancy. As an in-situ treatment
      appreciation of any signs of recurrence is critical for improving long-term
      oncological outcomes. Volumetry has been recognized as having advantages over
      orthogonal measurements in the response assessment of malignant lesions. Our
      study set out to look at the normal involution of an ablation zone (AZ) both
      volumetrically and morphologically to see if this information might aid the
      detection of local tumor progression. METHODS: Cases were identified
      retrospectively from our database of liver MWA. We identified 34 AZs in total, 18
      AZs in 16 hepatocellular carcinoma (HCC) patients with cirrhosis on imaging
      grounds and 13 AZs in patients with metastatic colorectal cancer. How these AZs
      developed over time was analyzed both morphologically and quantitatively using
      Siemens Syngo Via post-processing software. We used the software to produce
      volume measurements and short axis orthogonal measurements. A baseline
      measurement was taken on the first <30 day post-ablation scan and the
      chronological changes were then plotted. RESULTS: We saw differences between the
      cirrhotic and non-cirrhotic patients both in terms of morphological and
      volumetric changes. 12/13 non-cirrhotic AZs had a volume of <50% of the baseline
      scan within the first year. The cirrhotic patients were less predictable, but
      14/18 still shrunk to less than 50% of baseline volume in the first year.
      Orthogonal measurements were less useful in both groups. Qualitatively, there was
      initially a slightly less well-defined border to the AZ in the first 3 months,
      which became better defined over time and certainly over the first year of AZ
      involution. CONCLUSION: Volumetric analysis is a useful adjunct to conventional
      measurements and qualitative analysis of AZs. This can be reassuring when
      orthogonal measurements are static or difficult to interpret. Our preliminary
      data suggest that the normal pattern in a non-cirrhotic liver is that the AZ
      volume should drop below 50% of baseline at 1 year. Volumes in cirrhotic livers
      are less predictable, but the majority will still follow a similar pattern.
      Future studies could evaluate if failure to follow these patterns correlates with
      local tumor progression.

PMID- 27034070
TI  - The spectrum of autosomal dominant polycystic kidney disease in children and
      adolescents.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common
      hereditary renal disorder. It is characterized by the development of renal cysts
      and kidney enlargement and ultimately leads to renal failure typically in the
      sixth decade of life. Although most patients are asymptomatic until well into
      adulthood, renal cysts develop much earlier, often in utero. Significant renal
      anatomic and cystic expansion typically occurs before clinical manifestations in
      children and young adults with AKPKD. The cyst burden detected by imaging
      represents the minority of cyst burden, and renal and cardiovascular
      abnormalities are the most common manifestations in children with ADPKD. Here we
      review the molecular pathogenesis of ADPKD, discuss the screening, diagnosis and
      clinical manifestations of this renal disorder in childhood and adolescents and
      review treatment options and potential therapies currently being tested.

PMID- 27034072
TI  - The comparison of CT fistulography and MR imaging of perianal fistulae with
      surgical findings: a case-control study.
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic efficacies of
      CT fistulography and MRI, in the diagnostic work-up of perianal fistula patients.
      MATERIALS AND METHODS: All 41 patients who were included in the study (36 males
      and 5 females, with an average age of 41 years) underwent CT fistulography and
      MRI examinations prior to surgery. The fistula characteristics obtained from
      these examinations were compared with the surgical findings. The comparative
      results were evaluated by means of the Kappa analysis method. RESULTS: CT
      fistulography predicted the correct perianal fistula classification in 30 (73.1%)
      of the 41 patients, whereas MRI correctly defined fistula classification in 38
      (92.7%) of these patients (the K values were 0.621 and 0.896, respectively; with
      p < 0.001). CT fistulography depicted 29 secondary extensions in 16 patients,
      whereas MR imaging revealed 28 secondary extensions in 15 patients. A substantial
      agreement was found between surgical findings and two modalities (K value was
      0.789 and 0.793 for CT fistulography and MRI, respectively, with a p value <
      0.001). In terms of locations of internal openings, CT fistulography was able to
      detect the locations in 28 patients (68.2%), whereas MRI was more successful in
      this aspect, with a number of 35 patients (85.3%). Granulation tissues,
      inflammation and edema around the fistula, abscesses, and fistular wall fibrosis
      were also evaluated. CONCLUSION: CT fistulography and MRI have different
      advantages in the diagnosis of perianal fistulas. A good command of knowledge
      concerning the issue may be a key factor in modality decision.

PMID- 27034073
TI  - Abbreviation of Percutaneous Nephrolithotomy: PCNL or PNL?

PMID- 27034074
TI  - Chemical composition of groundwater/drinking water and oncological disease
      mortality in Slovak Republic.
AB  - This study deals with the analysis of relationship between chemical composition
      of the groundwater/drinking water and the data on mortality from oncological
      diseases (MOD) in the Slovak Republic. Primary data consist of the Slovak
      national database of groundwater analyses (20,339 chemical analyses, 34 chemical
      elements/compounds) and data on MOD (17 health indicators) collected for the 10
      year period (1994-2003). The chemical and health data were unified in the same
      form and expressed as the mean values for each of 2883 municipalities within the
      Slovak Republic. Pearson and Spearman correlation as well as artificial neural
      network (ANN) methods were used for analysis of the relationship between chemical
      composition of groundwater/drinking water and MOD. The most significant chemical
      elements having influence on MOD were identified together with their limit values
      (limit and optimal contents). Based on the results of calculations, made through
      the neural networks, the following eight chemical elements/parameters in the
      groundwater were defined as the most significant for MOD: Ca + Mg (mmol l-1), Ca,
      Mg, TDS, Cl, HCO3, SO4 and NO3. The results document the highest relationship
      between MOD and groundwater contents of Ca + Mg (mmol l-1), Ca and Mg. We observe
      increased MOD with low (deficit) contents of these three parameters of
      groundwater/drinking water. The following limit values were set for the most
      significant groundwater chemicals/parameters: Ca + Mg 1.73-5.85 mmol l-1, Ca 60.5
      196.8 mg l-1 and Mg 25.6-35.8 mg l-1. At these concentration ranges, the
      mortality for oncological diseases in the Slovak Republic is at the lowest
      levels. These limit values are about twice higher in comparison with the current
      Slovak valid guideline values for the drinking water.

PMID- 27034075
TI  - On the small angle twist sub-grain boundaries in Ti3AlC2.
AB  - Tilt-dominated grain boundaries have been investigated in depth in the
      deformation of MAX phases. In stark contrast, another important type of grain
      boundaries, twist grain boundaries, have long been overlooked. Here, we report on
      the observation of small angle twist sub-grain boundaries in a typical MAX phase
      Ti3AlC2 compressed at 1200  degrees C, which comprise hexagonal screw dislocation
      networks formed by basal dislocation reactions. By first-principles
      investigations on atomic-scale deformation and general stacking fault energy
      landscapes, it is unequivocally demonstrated that the twist sub-grain boundaries
      are most likely located between Al and Ti4f (Ti located at the 4f Wyckoff sites
      of P63/mmc) layers, with breaking of the weakly bonded Al-Ti4f. The twist angle
      increases with the increase of deformation and is estimated to be around 0.5
      degrees  for a deformation of 26%. This work may shed light on sub-grain
      boundaries of MAX phases, and provide fundamental information for future atomic
      scale simulations. 

PMID- 27034078
TI  - [Cryoglobulinemic vasculitis].
AB  - Cryoglobulinemic vasculitis is a disease of the small arteries and affects the
      skin, joints, peripheral nerves, kidneys and other organs. Even small amounts of
      cryoglobulins can lead to severe impairment for the patient but the detection of
      such low amounts of cryoglobulins can be difficult. The causes of
      cryoglobulinemic vasculitis include monoclonal hematological diseases, autoimmune
      diseases and chronic infections. Therapy involves treatment of the underlying
      disease and glucocorticoids, rituximab and plasmapheresis depending on the
      severity of the vasculitis. Recognition of typical clinical symptoms is essential
      in order to initiate appropriate laboratory diagnostic procedures. Sometimes many
      investigations are necessary. In the absence of clinical trials treatment
      recommendations can often only be derived from registry data. 

PMID- 27034076
TI  - [Caspase-1 regulates autoinflammation in rheumatic diseases].
AB  - Caspase-1 is an integral regulator of the innate immune system. Its core
      functions are the processing and secretion of the proinflammatory cytokines
      interleukin 1beta (IL-1 beta) and IL-18 and the initiation of proinflammatory
      cell death, which is referred to as pyroptosis. Activation of caspase-1 plays a
      pivotal role during immune defense mechanisms against infections by the innate
      immune system. Dysregulated activation of caspase-1 has been recognized to be
      involved in the pathophysiology of a constantly increasing number of inflammatory
      diseases. This article gives an overview of the regulation and function of
      caspase-1 and its involvement in monogenic, polygenic and/or polyetiological
      rheumatic diseases. 

PMID- 27034079
TI  - Additional Cavity Shaving at the Time of Breast-Conserving Surgery Enhances
      Accuracy of Margin Status Examination.
AB  - PURPOSE: We addressed the impact of separate cavity margin excision (shaving)
      during breast-conserving surgery (BCS) for breast cancer on specimen volume,
      tumor margin clearance, re-excision rate, local recurrence and survival. METHODS:
      A retrospective case-matched study was performed on 298 women with stage 0-III
      breast cancer; 179 patients received shaving (shaving + lumpectomy group; SLG)
      and 119 patients did not (lumpectomy group; LG). RESULTS: The two groups had
      similar baseline characteristics. The median volume of surgical specimen was
      131.9 cc in the SLG versus 134.8 cc in the LG (p = 0.81), and surgical margins
      were tumor-free in 90.7 % of cases in the LG versus 92.7 % in the SLG (87.1 %
      before shaving) (p = 0.69). The re-excision rate was 14.3 % in the LG versus 10.6
      % in the SLG (p = 0.44). In the SLG, shaving spared 10 (5.6 %) patients from
      reoperation (positive lumpectomy margins but tumor-free shaving margins) (p =
      0.11), and only 2/19 (10.5 %) patients in the SLG had tumor-free response at
      histological examination of re-excised margins compared with 10/17 (58.8 %) cases
      in the LG (p = 0.004). Tumor in shavings was found in 44/156 (28.2 %) patients
      having tumor-free lumpectomy margins. At multivariate analysis, distance of tumor
      from lumpectomy margins, tumor multifocality, receptor status, and tumor size
      were related to tumor persistence in shavings. Median follow-up was 27 months
      (range 23-35), and two patients had tumor relapse in the SLG versus none in the
      LG (p = 0.16). Overall survival was 100 % in both groups. CONCLUSIONS: Shaving
      does not significantly decrease the re-excision rate but provides wider clear
      margins in most procedures. It ensures more accurate margin examination and
      decreases false-positive margin rate, without any increase in removed breast
      tissue volume.

PMID- 27034080
TI  - Results and Survival of Locally Advanced AJCC 7th Edition T4a Laryngeal Squamous
      Cell Carcinoma Treated with Primary Total Laryngectomy and Postoperative
      Radiotherapy.
AB  - PURPOSE: The objective of this study was to analyze the results and survival of
      patients with T4a laryngeal squamous cell carcinoma (SCC) treated, according to
      clinical practice guidelines, with total laryngectomy and postoperative
      radiotherapy (TL-PORT) in a large and homogeneous series. METHODS: Initial
      staging assessment, treatment details, pathologic features, follow-up, and
      patterns of recurrence were retrospectively reviewed in a large series of 100
      patients treated in our center between 2001 and 2013 for T4a laryngeal SCC with
      TL-PORT. RESULTS: Two-, 5-, and 10-year overall survival rates were 65, 52.4, and
      33.3 %, respectively, while 2-, 5-, and 10-year disease-free survival rates were
      55, 42.6, and 31.8 %, respectively. In addition, 2-, 5-, and 10-year locoregional
      control rates were 77, 74, and 65.9 %, respectively. Central lymph node
      involvement was associated with pathologic subglottic extension (p = 0.01), lysis
      of the cricoid cartilage (p = 0.03), and tracheal extension (p = 0.02).
      Extracapsular spread of central lymph node metastases, the main prognostic factor
      identified by multivariate analysis, was associated with decreased locoregional
      control and survival rates. CONCLUSION: In this homogenously treated cohort, with
      consistent guideline application, surgery for T4a larynx cancer remains a
      standard of care, with current results used as a benchmark.

PMID- 27034081
TI  - Mechanistic studies of the agmatine deiminase from Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive food-borne pathogen that is capable of
      living within extreme environments (i.e. low temperatures and pH). This ability
      to survive in such conditions may arise, at least in part, from agmatine
      catabolism via the agmatine deiminase system (AgDS). This catabolic pathway
      utilizes an agmatine deiminase (AgD) to hydrolyse agmatine into N
      carbamoylputrescine (NCP), with concomitant release of ammonia, which increases
      the pH, thus mitigating the ill effects of the acidic environment. Given the
      potential significance of this pathway for cell survival, we set out to study the
      catalytic mechanism of the AgD encoded by L. monocytogenes In the present paper,
      we describe the catalytic mechanism employed by this enzyme based on pH profiles,
      pKa measurements of the active site cysteine and solvent isotope effects (SIE).
      In addition, we report inhibition of this enzyme by two novel AgD inhibitors,
      i.e. N-(4-aminobutyl)-2-fluoro-ethanimidamide (ABFA) and N-(4-aminobutyl)-2
      chloro-ethanimidamide (ABCA). In contrast with other orthologues, L.
      monocytogenes AgD does not use the reverse protonation or substrate-assisted
      mechanism, which requires an active site cysteine with a high pKa and has been
      commonly seen in other members of the guanidinium-modifying enzyme (GME)
      superfamily. Instead, the L. monocytogenes AgD has a low pKa cysteine in the
      active site leading to an alternative mechanism of catalysis. This is the first
      time that this mechanism has been observed in the GME superfamily and is
      significant because it explains why previously developed mechanism-based
      inactivators of AgDs are ineffective against this orthologue.

PMID- 27034082
TI  - Proton-pump inhibitors adverse effects: a review of the evidence and position
      statement by the Sociedad Espanola de Patologia Digestiva.
AB  - INTRODUCTION: In the last few years a significant number of papers have related
      the use of proton-pump inhibitors (PPIs) to potential serious adverse effects
      that have resulted in social unrest. OBJECTIVE: The goal of this paper was to
      provide a literature review for the development of an institutional position
      statement by Sociedad Espanola de Patologia Digestiva (SEPD) regarding the safety
      of long-term PPI use. MATERIAL AND METHODS: A comprehensive review of the
      literature was performed to draw conclusions based on a critical assessment of
      the following: a) current PPI indications; b) vitamin B12 deficiency and
      neurological disorders; c) magnesium deficiency; d) bone fractures; e) enteric
      infection and pneumonia; f) interactions with thienopyridine derivatives; e)
      complications in cirrhotic patients. RESULTS: Current PPI indications have
      remained unchanged for years now, and are well established. A general screening
      of vitamin B12 levels is not recommended for all patients on a PPI; however, it
      does seem necessary that magnesium levels be measured at therapy onset, and then
      monitored in subjects on other drugs that may induce hypomagnesemia. A higher
      risk for bone fractures is present, even though causality cannot be concluded for
      this association. The association between PPIs and infection with Clostridium
      difficile is mild to moderate, and the risk for pneumonia is low. In patients
      with cardiovascular risk receiving thienopyridines derivatives it is prudent to
      adequately consider gastrointestinal and cardiovascular risks, given the absence
      of definitive evidence regardin potential drug-drug interactions; if
      gastrointestinal risk is found to be moderate or high, effective prevention
      should be in place with a PPI. PPIs should be cautiously indicated in patients
      with decompensated cirrhosis. CONCLUSIONS: PPIs are safe drugs whose benefits
      outweigh their potential side effects both short-term and long-term, provided
      their indication, dosage, and duration are appropriate.

PMID- 27034083
TI  - Efficacy and safety of helical tomotherapy with daily image guidance in anal
      canal cancer patients.
AB  - Background and purpose Intensity-modulated radiotherapy (IMRT), also using
      volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques,
      has been only recently introduced for treating anal cancer patients. We report
      efficacy and safety HT, and daily image-guided RT (IGRT) for anal cancer.
      Materials and methods We retrospectively analyzed efficacy and toxicity of HT
      with or without chemotherapy for anal cancer patients. Local control (LC) and
      grade 3 or more toxicity rate (CTC-AE v.4.0) were the primary endpoints. Overall
      (OS), disease-free (DFS), and colostomy-free survival (CFS) are also reported.
      Results Between October 2007 and May 2014, 78 patients were treated. Fifty
      patients presented a stage II or stage IIIA (UICC 2002), and 33 presented a N1-3
      disease. Radiotherapy consisted of 36 Gy (1.8 Gy/fraction) delivered on the
      pelvis and on the anal canal, with a sequential boost up to 59.4 Gy (1.8
      Gy/fraction) delivered to the anal and to nodal gross tumor volumes. Concomitant
      chemotherapy was delivered in 73 patients, mainly using mitomycin C and 5
      fluorouracil (n = 30) or mitomycin C and capecitabine combination (n = 37). After
      a median follow-up period of 47 months (range 3-75), the five-year LC rate was
      83.8% (95% CI 76.2-91.4%). Seven patients underwent a colostomy because of local
      recurrence (n = 5) or pretreatment dysfunction (n = 2). Overall incidence of
      grade 3 acute toxicity was 24%, mainly as erythema (n = 15/19) or diarrhea (n =
      7/19). Two patients presented a late grade 3 gastrointestinal toxicity (anal
      incontinence). No grade 4 acute or late toxicity was recorded. Conclusions HT
      with daily IGRT is efficacious and safe in the treatment of anal canal cancer
      patients, and is considered in our department standard of care in this clinical
      setting. 

PMID- 27034084
TI  - Tibiofemoral forces for the native and post-arthroplasty knee: relationship to
      maximal laxity through a functional arc of motion.
AB  - PURPOSE: Accurate soft tissue balance must be achieved to improve functional
      outcome after total knee arthroplasty (TKA). Sensor-integrated tibial trials have
      been introduced that allow real-time measurement of tibiofemoral kinematics
      during TKA. This study examined the interplay between tibiofemoral force and
      laxity, under defined intraoperative conditions, so as to quantify the kinematic
      behaviour of the CR femoral single-radius knee. METHODS: TKA was undertaken in
      eight loaded cadaveric specimens. Computer navigation in combination with sensor
      data defined laxity and tibiofemoral contact force, respectively, during manual
      laxity testing. Fixed-effect linear modelling allowed quantification of the
      effect for flexion angle, direction of movement and TKA implantation upon the
      knee. RESULTS: An inverse relationship between laxity and contact force was
      demonstrated. With flexion, laxity increased as contact force decreased under
      manual stress. Change in laxity was significant beyond 30 degrees  for coronal
      plane laxity and beyond 60 degrees  for rotatory laxity (p < 0.01). Rotational
      stress in mid-flexion demonstrated the greatest mismatch in inter-compartmental
      forces. Contact point position over the tibial sensor demonstrated paradoxical
      roll-forward with knee flexion. CONCLUSION: Traditional balancing techniques may
      not reliably equate to uniform laxity or contact forces across the tibiofemoral
      joint through a range of flexion and argue for the role of per-operative sensor
      use to aid final balancing of the knee.

PMID- 27034085
TI  - Factors affecting cartilage repair after medial opening-wedge high tibial
      osteotomy.
AB  - PURPOSE: This study documented the healing potential of degenerated articular
      cartilage after opening-wedge valgus high tibial osteotomy (HTO) in patients with
      osteoarthritis of the knee. It was hypothesized that regeneration of articular
      cartilage is affected by several factors, including preoperative cartilage
      degeneration grade, difference between the medial femoral condyle (MFC) and the
      medial tibial condyle (MTC), and postoperative knee alignment. METHODS: Medial
      opening-wedge valgus HTO was performed in 131 knees of 100 patients (mean age 66
      +/- 7.7 years). Initial arthroscopy was performed at the time of HTO, and a
      second-look arthroscopy was performed at the time of plate removal (20.8 +/- 6.5
      months after HTO). Status of articular cartilage was assessed according to the
      ICRS grade. Cartilage regeneration was also evaluated by the presence of newly
      formed cartilaginous tissue. All subjects were followed up postoperatively at 2
      years for assessment of clinical and radiographic outcomes. RESULTS: The number
      of subjects in ICRS grade 1/2/3/4 was significantly altered from 0/11/53/67
      preoperatively to 14/21/56/40 postoperatively in the MFC (P < 0.05) and
      0/12/62/57 preoperatively to 9/24/64/34 postoperatively in the MTC (P < 0.05).
      Newly formed cartilaginous tissue was found in 71 % of MFCs and 51 % of MTCs.
      Incidence of cartilage regeneration was significantly higher in lower BMI cases,
      MFC, preoperatively advanced ICRS grade and overcorrected knees. Age, gender and
      clinical outcomes did not affect cartilage regeneration. CONCLUSION: Cartilage
      regeneration in degenerated articular cartilage is induced after opening-wedge
      valgus HTO, which is affected by BMI, the difference between the MFC and MTC,
      preoperative cartilage degeneration grade, and postoperative limb alignment.
      Therefore, patient selection by BMI rather than age, and surgical techniques
      maintaining valgus knee alignment should be considered for cartilage
      regeneration. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 27034086
TI  - Clinical outcome is not affected by total knee arthroplasty alignment.
AB  - PURPOSE: This study aims to analyse the influence on total knee arthroplasty
      (TKA) clinical outcomes of biomechanical intra-operative computer-assisted
      surgery-measured parameters, together with radiographic and demographical data.
      METHODS: Between 2007 and 2009, 227 computer-assisted surgery (CAS) primary TKAs
      were performed in 219 consecutive patients. Information about gender, age and
      body mass index (BMI) was collected for each patient. Before knee replacement,
      all patients underwent a complete radiographic examination and passive flexion
      extension range of motion was recorded. All TKAs were implanted using an image
      free knee navigation system. Patients included in the study were evaluated at 3,
      6 and 12 months of follow-up and then yearly. At each follow-up, subjects were
      asked to answer the validated Italian version of the Knee Injury and
      Osteoarthritis Outcome Score. RESULTS: One hundred and eighty patients (187
      knees) had data available for analysis. Complications were reported in 13
      patients (7.0 %). Intra-operative CAS-measured parameters, together with age,
      BMI, gender, pre- and post-operative radiographic alignment, did not influence
      TKA clinical results at a mean 2 years of follow-up. On the other hand, higher
      post-operative flexion arc of movement was suggestive of better clinical
      outcomes. CONCLUSION: TKA clinical outcome is influenced by post-operative knee
      flexion, other than neutral mechanical limb alignment. Therefore, it is
      recommended to prefer TKA designs that allow high flexion and to encourage early
      physical rehabilitation. LEVEL OF EVIDENCE: IV.

PMID- 27034087
TI  - Why are bone and soft tissue measurements of the TT-TG distance on MRI different
      in patients with patellar instability?
AB  - PURPOSE: To determine whether the tibial tuberosity-to-trochlear groove distance
      (TT-TG) and patellar tendon-to-trochlear groove distance (PT-TG) are equal,
      whether the bony and cartilaginous points coincide in the trochlea, and whether
      the insertion of the PT coincides with the most anterior point of the TT in
      patients with patellar instability. METHODS: Fifty-three MRI scans of patients
      with patellar instability were examined. TT-TG and PT-TG were measured by three
      examiners in 31 knees. Additionally, the bone-cartilage distance in the trochlea
      [trochlear cartilage to trochlear bone (TC-TB)] and the distance between the mid
      point of the PT insertion and the most anterior point of the TT (PT-TT) were
      measured by one examiner. The intraclass correlation coefficient was used to
      evaluate the reliability of the measurements between the three examiners. The
      relationships between the measurements were determined, the means of the
      measurements were calculated, and the correlations between PT-TG and TT-TG, PT
      TT, and TC-TB were assessed. RESULTS: The ICC was above 0.8. PT-TG was 3.7 mm
      greater than TT-TG. The TC and TB coincided in 73 % of cases, and the mean TC-TB
      was 0.3 mm. The PT was lateral to the TT in 94 % of the cases, and the mean PT-TT
      was 3.4 mm. The Pearson's correlation coefficients between PT-TG and TT-TG, PT
      TT, and TC-TB were 0.946, 0.679, and 0.199, respectively. CONCLUSION: TT-TG
      underestimated PT-TG, primarily due to the lateralization of the PT insertion
      relative to the most anterior point of the TT. CLINICAL RELEVANCE: our study
      shows that in patients with patellar instability, there are differences in the
      absolute values of TT-TG and PT-TG, as previously reported for patients without
      patellar instability. Hence, normal cut-off values based on case-control studies
      of TT-TG cannot be equivalently used when measuring PT-TG to indicate TT
      medialization in patients with patellar instability. It is also important to note
      that the clinical outcomes cannot be directly compared between patients evaluated
      using TT-TG versus PT-TG measurements. LEVEL OF EVIDENCE: III.

PMID- 27034088
TI  - Sagittal plane tilting deformity of the patellofemoral joint: a new concept in
      patients with chondromalacia patella.
AB  - PURPOSE: The aims of this study were to evaluate sagittal plane alignment in
      patients with chondromalacia patella via magnetic resonance imaging (MRI),
      analyse the relationships between the location of the patellar cartilaginous
      lesions and sagittal alignment and finally investigate the relationships between
      the sagittal plane malalignment and patellofemoral loadings using by finite
      element analysis. METHODS: Fifty-one patients who were diagnosed with isolated
      modified Outerbridge grade 3-4 patellar chondromalacia based on MRI evaluation
      and 51 control subjects were evaluated. Chondromalacia patella patients were
      divided into three subgroups according to the chondral lesion location as
      superior, middle and inferior. The patella-patellar tendon angle (P-PT) was used
      for evaluation of sagittal alignment of patellofemoral joint. Each subgroup was
      compared with control group by using P-PT angle. To investigate the biomechanical
      effects of sagittal plane malpositioning on patellofemoral joint, bone models
      were created at 30 degrees , 60 degrees  and 90 degrees  knee flexion by using
      mean P-PT angles, which obtained from patients with chondromalacia patellae and
      control subjects. The total loading and contact area values of the patellofemoral
      joints were investigated by finite element analysis. RESULTS: The mean age of all
      participants was 52.9 +/- 8.2 years. The mean P-PT angle was significantly lower
      in chondromalacia group (142.1 degrees  +/- 3.6 degrees ) compared to control
      group (144.5 degrees  +/- 5.3 degrees ) (p = 0.008). Chondral lesions were
      located in superior, middle and inferior zones in 16, 20 and 15 patients,
      respectively. The mean P-PT angles in patients with superior (141.8 +/- 2.7) and
      inferior subgroups (139.2 +/- 2.3) were significantly lower than the values in
      the control group (p < 0.05). The contact area values were detected higher in
      models with chondromalacia than in the control models at the same flexion
      degrees. There were increased loadings at 30 degrees  and 90 degrees  flexions in
      the sagittal patellar tilt models. CONCLUSION: This study revealed that sagittal
      plain malpositioning of the patellofemoral joint might be related to
      chondromalacia, especially in the presence of lesions in the upper and lower part
      of the patella. This condition leads to supraphysiological loadings on the
      patellofemoral joint. Sagittal patellar tilt should be considered in the
      evaluation and management of patellar cartilage defects. Taking sagittal plane
      malalignment into consideration in patellofemoral joint evaluation will enable us
      to design new physical and surgical modalities. LEVEL OF EVIDENCE: IV.

PMID- 27034089
TI  - Assessment of Imatinib in the treatment of chronic myeloid leukemia in Gabon: a
      cohort of 17 cases.
AB  - The prognosis for chronic myeloid leukemia, the first hematologic malignancy for
      which successful targeted therapy has been developed, has changed markedly in the
      West. In developing countries, however, prognosis remains poor, mainly because of
      lack of access to treatment. The effort made by some nongovernmental
      organizations to distribute first-generation tyrosine kinase inhibitors free of
      charge has changed this situation in some regions, notably in sub-Saharan Africa
      and Gabon in particular. We report the results in a cohort of 17 patients. 

PMID- 27034090
TI  - Novel Use of Pudendal Neuromodulation in a Pediatric Patient With Caudal
      Regression and Partial Sacral Agenesis for Refractory Bowel Bladder Dysfunction.
AB  - Sacral neuromodulation (SNM) has been used off-label in the United States for
      over a decade in the pediatric population. Many published studies have
      demonstrated efficacy with SNM in this population; however, a significant number
      of children with refractory bowel bladder dysfunction (BBD) also have underlying
      comorbidities. Children with certain spinal abnormalities pose a problem for the
      urologist treating BBD. Patients with caudal regression can have various sacral
      anomalies, making SNM challenging or impossible. We present the first case in the
      United States of pudendal neuromodulation in a pediatric BBD patient with caudal
      regression. 

PMID- 27034091
TI  - Relationships Between Deprivation and the Self-Reported Health of Older People in
      Northern Ireland.
AB  - OBJECTIVE: There are few studies on relationships between deprivation and the
      self-reported health of people aged above 64 years, and no studies fully
      representative of Northern Ireland's older population. This article addresses
      this gap. METHOD: Deprivation of older people as reported in the 2001 and 2011
      Censuses and the relationship with self-reported health are analyzed over a 10
      year span using multilevel modeling. The data are from the Northern Ireland
      Longitudinal Study (NILS) linked to 2001-2011 Census returns. Deprivation
      measures include housing tenure; property value; access to a car; and
      educational, employment, and area-level income deprivation. RESULTS: Older people
      suffering deprivation face a significant health disadvantage over a 10-year time
      span. DISCUSSION: This health disadvantage is stronger in men than in women,
      likely due to conservative gender roles that are prevalent among Northern
      Ireland's older population, leading to psychological distress especially among
      deprived men. The analysis found strongly significant area-level effects,
      aggravating the health impact of deprivation.

PMID- 27034092
TI  - Shaped Ir-Ni bimetallic nanoparticles for minimizing Ir utilization in oxygen
      evolution reaction.
AB  - Shaped Ir-Ni bimetallic nanoparticles were synthesized and used for
      electrocatalytic oxygen evolution reaction (OER). The obtained bimetallic
      nanoparticles showed significantly enhanced Ir mass activity and durability
      compared with Ir nanoparticles. 

PMID- 27034093
TI  - Economic impact of lower-limb osteoarthritis worldwide: a systematic review of
      cost-of-illness studies.
AB  - OBJECTIVE: An overview of the economic consequences - overall costs as well as
      cost breakdown (direct and indirect) - of hip and knee osteoarthritis (OA)
      worldwide. METHODS: A systematic literature search of EMBASE, MEDLINE, Scopus and
      Cochrane databases for articles was performed independently by two
      rheumatologists who used the same predefined eligible criteria. Papers without
      abstracts and in languages other than English or French were excluded. Extracted
      costs were converted to an annual cost and to 2013 euros (?) by using the
      Consumer Price Index of the relevant countries and the 2013 Purchasing Power
      Parities between these countries and the European Union average. RESULTS: A total
      of 45 abstracts were selected, and 32 articles were considered for the review.
      The studied populations were heterogeneous: administrative, hospital and national
      health survey data. Annual total costs per patient ranged from 0.7 to 12 k?,
      direct costs per patient from 0.5 to 10.9 k? and indirect costs per patient from
      0.2 to 12.3 k?. The weighted average annual costs per patient living with knee
      and hip OA were 11.1, 9.5 and 4.4 k? for total, direct and indirect costs,
      respectively. CONCLUSIONS: This review highlights the heterogeneity of studies
      and lack of methodologic consensus to obtain reliable cost-of-illness estimates
      for lower-limb OA. However, costs induced by the disease seem substantial and
      deserve to be more extensively explored.

PMID- 27034094
TI  - Structural and activity characterization of human PHPT1 after oxidative
      modification.
AB  - Phosphohistidine phosphatase 1 (PHPT1), the only known phosphohistidine
      phosphatase in mammals, regulates phosphohistidine levels of several proteins
      including those involved in signaling, lipid metabolism, and potassium ion
      transport. While the high-resolution structure of human PHPT1 (hPHPT1) is
      available and residues important for substrate binding and catalytic activity
      have been reported, little is known about post-translational modifications that
      modulate hPHPT1 activity. Here we characterize the structural and functional
      impact of hPHPT1 oxidation upon exposure to a reactive oxygen species, hydrogen
      peroxide (H2O2). Specifically, liquid chromatography-tandem mass spectrometry was
      used to quantify site-specific oxidation of redox-sensitive residues of hPHPT1.
      Results from this study revealed that H2O2 exposure induces selective oxidation
      of hPHPT1 at Met95, a residue within the substrate binding region. Explicit
      solvent molecular dynamics simulations, however, predict only a minor effect of
      Met95 oxidation in the structure and dynamics of the apo-state of the hPHPT1
      catalytic site, suggesting that if Met95 oxidation alters hPHPT1 activity, then
      it will do so by altering the stability of an intermediate state. Employing a
      novel mass spectrometry-based assay, we determined that H2O2-induced oxidation
      does not impact hPHPT1 function negatively; a result contrary to the common
      conception that protein oxidation is typically a loss-of-function modification. 

PMID- 27034095
TI  - The rationale for rating risk of bias should be fully reported: response.

PMID- 27034096
TI  - The rationale for rating risk of bias should be fully reported.

PMID- 27034097
TI  - Do the lung segments exist continuously from the early stage of the embryonic
      period as units?
AB  - OBJECTIVES: Although various types of segmentectomy are frequently performed for
      resecting lung tumours at present, there is no clear answer to the question what
      kind of segmentectomy would be more efficient for performing lymphadenectomy.
      Learning the embryological mechanism of the segment formation could be one of the
      methods for selecting the surgical procedure. To investigate the developmental
      mechanism of the lung, this study focused on 'sharing structure', a unique 3D
      structure consisting of the bronchi and pulmonary arteries. In the structure, two
      arteries from different directions, after straddling the bronchus in the central
      part, share one bronchial tree at the peripheral part. METHODS: Using computed
      tomography data obtained before segmentectomy, this study observed the 'sharing
      structure' in 193 left and right upper lobe cases. This study investigated the
      relationship between the segmental arterial types and the straddled bronchi,
      which were straddled by the pulmonary arteries found in the centre of the sharing
      structure. RESULTS: In the right upper lobes, the straddled bronchi were anterior
      segmental bronchi. In the left upper lobes, however, the straddled bronchi of the
      lingular interlobar pulmonary artery type contained no anterior segmental
      bronchi. But, the straddled bronchi of lingular mediastinal pulmonary artery type
      contained anterior segmental bronchi in all cases. CONCLUSIONS: Although
      pulmonary arteries in almost all sharing structures in the right upper lobes
      straddled anterior bronchi, those in mediastinal type and interlobar type in the
      left upper lobe were found to straddle the anterior and apicoposterior bronchi,
      respectively. These findings indicated that the interlobar type was speculated to
      be rotating mediastinal type backward in the embryonic period. This study
      strongly suggested a new concept that 'the lung segments never continuously exist
      from the early stage of the embryonic period as units, but they are only simple
      units artificially named by their prevailing bronchial branching patterns'.
      Therefore, during segmentectomy including lymphadenectomy for pulmonary tumours,
      the retrieval of the branching patters of pulmonary arteries could allow the
      segmentectomy to become more efficient with considering the formations of lung
      lobes.

PMID- 27034099
TI  - Substantial slice of L4.2bn IT fund must go to general practice, say GP leaders.

PMID- 27034098
TI  - Late outcome after paediatric heart transplantation in Finland.
AB  - OBJECTIVES: We studied the long-term survival and rejection episodes of
      paediatric heart transplant recipients. METHODS: We included all paediatric
      patients (<=18 years) who underwent heart transplantation during 1991-2014 in
      Finland. Data were obtained retrospectively from a paediatric cardiac surgery
      database. Patient status was received from the Finnish population registry. All
      patients underwent yearly routine postoperative endomyocardial biopsies and
      coronary angiographies. RESULTS: Between 1991 and 2014, 68 heart transplantations
      were performed. The early mortality (<30 days after surgery) rate was 10% and
      follow-up coverage was 100%. The 10- and 15-year survival rates for all patients
      were 68% (95% confidence internal, CI, 56-80%) and 65% (95% CI 53-78%),
      respectively, including early mortality. The 1-year survival rate was 100% when
      excluding early operative mortality. Indications for heart transplantation were
      cardiomyopathy in 57% and cardiac malformations in 43% of patients, with similar
      long-term survival between the groups. During 23 years of follow-up, 43 patients
      (70%) had at least one rejection episode and 17 patients (29%) at least a grade 1
      coronary artery vasculopathy finding. Patients with early rejection episodes (<3
      months) had a higher incidence of late rejection episodes (P = 0.025). Older age
      at operation was a significant risk factor for the development of coronary artery
      vasculopathy (hazard ratio 1.1, 95% CI 1.0-1.3, P = 0.012). CONCLUSIONS: First
      year survival was excellent. Asymptomatic rejection episodes were common among
      patients. Early rejection episodes are a risk factor for late rejection episodes
      and show a trend towards an increased risk of late death. Coronary artery
      vasculopathy remains a major challenge for late graft survival.

PMID- 27034100
TI  - Our early experience of the Corin Minihip prosthesis.
AB  - PURPOSE: Although there have been several varieties of short-stem hip prosthesis
      in the market, there have been no published clinical results of the Corin MiniHip
      (Corin, Cirencester, UK) to date. The aim of this study is to describe our early
      results and experience of this stem in a nondesigner, single-surgeon series;
      calculate 5-year survival with stem revision as an endpoint; evaluate
      complications and early revisions; and assess radiolucency and stem subsidence at
      the latest follow-up review. METHODS: Over a 5-year period, 275 MiniHip were
      implanted in 239 patients. The mean age of the patients was 63 years (range 20
      84); mean follow-up was 37 months (range 12-72 months). RESULTS: The mean Harris
      Hip Score and Oxford Hip Score improved significantly to 87 (range 49-100) and 41
      (range 32-48) at the final follow-up (p = 0.038; p = 0.017). There were 9
      intraoperative calcar fractures (3%) of which only 1 required cerlage wiring. 10
      patients died in our series and none were lost to follow-up. 2 patients had their
      stem revised for failure of fixation (secondary to possible undersizing) and
      sink. The risk of revision was 0.73% at 5 years. The Kaplan Meier estimate of
      survivorship of cumulative failure gave an implant survival rate of 99.3% (95%
      confidence interval [CI], 27.0-100) at 5 years for revision for any reason as the
      endpoint. CONCLUSIONS: This novel, short-stem prosthesis has shown good survival
      in the short term, similar to other short-stem prostheses currently available. We
      describe the largest series in the literature of this prosthesis.

PMID- 27034101
TI  - Reliability in the diagnosis of femoroacetabular impingement and dysplasia among
      hip surgeons: role of surgeon volume and experience.
AB  - PURPOSE: To evaluate the degree of inter-rater agreement in identifying important
      radiographic features of femoroacetabular impingement (FAI) and hip dysplasia. In
      addition, the effect of supplementary investigations (CT and/or MRI) and clinical
      experience of the observer was determined. METHODS: During the British Hip
      Society meeting 2013 participants were asked to remark on various radiological
      parameters of FAI and dysplasia, make a diagnosis, and recommended treatment.
      Free-Marginal Multirater Kappa analysis was performed to determine multi-rater
      agreement. RESULTS: The 'crossover sign', 'ischial spine sign' and 'lateral
      centre-edge angle' were found to have the highest inter-rater agreement. For the
      whole group only fair agreement was seen for the diagnosis of type of FAI (kappa
      = 0.3) and dysplasia (kappa = 0.3) after plain radiographs with supplementary
      investigations being only marginally helpful in improving the diagnosis of type
      of FAI (kappa = 0.4). In contrast, high-volume hip preservation surgeons had a
      substantial improvement in diagnosis after supplementary investigations (type of
      FAI kappa = 0.75, and dysplasia (kappa = 0.65). CONCLUSIONS: Our study shows that
      agreement on diagnosis and treatment on the basis of plain radiographs is low
      amongst general hip surgeons. This improved with surgeon volume and experience,
      suggesting that protocols for diagnosis of these conditions need to be altered as
      assessment appears to be rather subjective.

PMID- 27034102
TI  - Premature diagnostic closure in palliative medicine.

PMID- 27034103
TI  - An influential factor for external radiation dose estimation for residents after
      the Fukushima Daiichi Nuclear Power Plant accident-time spent outdoors for
      residents in Iitate Village.
AB  - Many studies have been conducted on radiation doses to residents after the
      Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Time spent outdoors is an
      influential factor for external dose estimation. Since little information was
      available on actual time spent outdoors for residents, different values of
      average time spent outdoors per day have been used in dose estimation studies on
      the FDNPP accident. The most conservative value of 24 h was sometimes used, while
      2.4 h was adopted for indoor workers in the UNSCEAR 2013 report. Fukushima
      Medical University has been estimating individual external doses received by
      residents as a part of the Fukushima Health Management Survey by collecting
      information on the records of moves and activities (the Basic Survey) after the
      accident from each resident. In the present study, these records were analyzed to
      estimate an average time spent outdoors per day. As an example, in Iitate
      Village, its arithmetic mean was 2.08 h (95% CI: 1.64-2.51) for a total of 170
      persons selected from respondents to the Basic Survey. This is a much smaller
      value than commonly assumed. When 2.08 h is used for the external dose
      estimation, the dose is about 25% (23-26% when using the above 95% CI) less
      compared with the dose estimated for the commonly used value of 8 h. 

PMID- 27034104
TI  - Experimental investigation of the information entropic Bell inequality.
AB  - Inequalities of information entropic play a fundamental role in information
      theory and have been employed effectively in finding bounds on optimal rates of
      various information-processing tasks. In this paper, we perform the first
      experimental demonstration of the information-theoretic spin-1/2 inequality using
      the high-fidelity entangled state. Furthermore, we study the evolution of
      information difference of entropy when photons passing through different noisy
      channels and give the experimental rules of the information difference
      degradation. Our work provides an new essential tool for quantum information
      processing and measurement, and offers new insights into the dynamics of quantum
      correlation in open systems. 

PMID- 27034105
TI  - Exploring the Definition of Acute Low Back Pain: A Prospective Observational
      Cohort Study Comparing Outcomes of Chiropractic Patients With 0-2, 2-4, and 4-12
      Weeks of Symptoms.
AB  - OBJECTIVE: The purpose of this study was to compare improvement rates in patients
      with low back pain (LBP) undergoing chiropractic treatment with 0-2 weeks vs 2-4
      and 4-12 weeks of symptoms. METHODS: This was a prospective cohort outcome study
      with 1-year follow-up including adult acute (symptoms 0-4 weeks) LBP patients.
      The numerical rating scale for pain (NRS) and Oswestry questionnaire were
      completed at baseline, 1 week, 1 month, and 3 months after starting treatment.
      The Patient Global Impression of Change (PGIC) scale was completed at all follow
      up time points. At 6 months and 1 year, NRS and PGIC data were collected. The
      proportion of patients reporting relevant "improvement" (PGIC scale) was compared
      between patients having 0-2 and 2-4 weeks of symptoms using the chi(2) test at
      all data collection time points. The unpaired t test compared NRS and Oswestry
      change scores between these 2 groups. RESULTS: Patients with 0-2 weeks of
      symptoms were significantly more likely to "improve" at 1 week, 1 month, and 6
      months compared with those with 2-4 weeks of symptoms (P < .015). Patients with 0
      2 weeks of symptoms reported significantly higher NRS and Oswestry change scores
      at all data collection time points. Outcomes for patients with 2-4 weeks of
      symptoms were similar to patients having 4-12 weeks of symptoms. CONCLUSION: The
      time period 0-4 weeks as the definition of "acute" should be challenged. Patients
      with 2-4 weeks of symptoms had outcomes similar to patients with subacute (4-12
      weeks) symptoms and not with patients reporting 0-2 weeks of symptoms.

PMID- 27034106
TI  - Symptomatic, MRI Confirmed, Lumbar Disc Herniations: A Comparison of Outcomes
      Depending on the Type and Anatomical Axial Location of the Hernia in Patients
      Treated With High-Velocity, Low-Amplitude Spinal Manipulation.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether specific MRI
      features, such as axial location and type of herniation, are associated with
      outcomes of symptomatic lumbar disc herniation patients treated with spinal
      manipulation therapy (SMT). METHODS: MRI and treatment outcome data from 68
      patients were included in this prospective outcomes study. Pain numerical rating
      scale (NRS) and Oswestry physical disability questionnaire (OPDQ) levels were
      measured at baseline. The Patients Global Impression of Change scale, the NRS and
      the OPDQ were collected at 2 weeks, 1, 3, 6 months and 1 year. One radiologist
      and 2 chiropractic medicine master's degree students analyzed the MRI scans
      blinded to treatment outcomes. kappa statistics assessed inter-rater reliability
      of MRI diagnosis. The proportion of patients reporting relevant improvement at
      each time point was compared based on MRI findings using the chi-square test. The
      t test and ANOVA compared the NRS and OPDQ change scores between patients with
      various MRI abnormalities. RESULTS: A higher proportion of patients with disc
      sequestration reported relevant improvement at each time point but this did not
      quite reach statistical significance. Patients with disc sequestration had
      significantly higher reduction in leg pain at 1 month compared to those with
      extrusion (P = .02). Reliability of MRI diagnosis ranged from substantial to
      perfect (K = .733-1.0). CONCLUSIONS: Patients with sequestered herniations
      treated with SMT to the level of herniation reported significantly higher levels
      of leg pain reduction at 1 month and a higher proportion reported improvement at
      all data collection time points but this did not reach statistical significance.

PMID- 27034107
TI  - Cross-Sectional Analysis of Per Capita Supply of Doctors of Chiropractic and
      Opioid Use in Younger Medicare Beneficiaries.
AB  - OBJECTIVE: The purpose of this study was to determine whether the per-capita
      supply of doctors of chiropractic (DCs) or Medicare spending on chiropractic care
      was associated with opioid use among younger, disabled Medicare beneficiaries.
      METHODS: Using 2011 data, at the hospital referral region level, we correlated
      the per-capita supply of DCs and spending on chiropractic manipulative therapy
      (CMT) with several measures of per-capita opioid use by younger, disabled
      Medicare beneficiaries. RESULTS: Per-capita supply of DCs and spending on CMT
      were strongly inversely correlated with the percentage of younger Medicare
      beneficiaries who had at least 1, as well as with 6 or more, opioid prescription
      fills. Neither measure was correlated with mean daily morphine equivalents per
      opioid user or per chronic opioid user. CONCLUSIONS: A higher per-capita supply
      of DCs and Medicare spending on CMT were inversely associated with younger,
      disabled Medicare beneficiaries obtaining an opioid prescription. However,
      neither measure was associated with opioid dosage among patients who obtained
      opioid prescriptions.

PMID- 27034108
TI  - Development of a Linked Segment Model to Derive Patient Low Back Reaction Forces
      and Moments During High-Velocity Low-Amplitude Spinal Manipulation.
AB  - OBJECTIVE: The purpose of this paper is to present the experimental setup, the
      development, and implementation of a new scalable model capable of efficiently
      handling data required to determine low back kinetics during high-velocity low
      amplitude spinal manipulation (HVLA-SM). METHODS: The model was implemented in
      Visual3D software. All contact forces and moments between the patient and the
      external environment (2 clinician hand contact forces, 1 contact force between
      the patient and the treatment table), the patient upper body kinematics, and
      inertial properties were used as input. Spine kinetics and kinematics were
      determined from a single HVLA-SM applied to one healthy participant in a right
      side-lying posture to demonstrate the model's utility. The net applied force was
      used to separate the spine kinetic and kinematic time-series data from the HVLA
      SM into preload as well as early and late impulse phases. RESULTS: Time-series
      data obtained from the HVLA-SM procedure showed that the participant's spine
      underwent left axial rotation, combined with extension, and a reduction in left
      lateral bending during the procedure. All components of the reaction force, as
      well as the axial twist and flexion/extension reaction moments demonstrated a
      sinusoidal pattern during the early and late impulse phases. During the early
      impulse phase, the participant's spine experienced a leftward axial twisting
      moment of 37.0 Nm followed by a rightward moment of -45.8 Nm. The lateral bend
      reaction moment exhibited a bimodal pattern during the early and late impulse
      phases. CONCLUSION: This model was the first attempt to directly measure all
      contact forces acting on the participant/patient's upper body, and integrate them
      with spine kinematic data to determine patient low back reaction forces and
      moments during HVLA-SM in a side-lying posture. Advantages of this model include
      the brevity of data collection (<1 hour), and adaptability for different patient
      anthropometries and clinician-patient contacts.

PMID- 27034109
TI  - A low-cost hierarchical nanostructured beta-titanium alloy with high strength.
AB  - Lightweighting of automobiles by use of novel low-cost, high strength-to-weight
      ratio structural materials can reduce the consumption of fossil fuels and in turn
      CO2 emission. Working towards this goal we achieved high strength in a low cost
      beta-titanium alloy, Ti-1Al-8V-5Fe (Ti185), by hierarchical nanostructure
      consisting of homogenous distribution of micron-scale and nanoscale alpha-phase
      precipitates within the beta-phase matrix. The sequence of phase transformation
      leading to this hierarchical nanostructure is explored using electron microscopy
      and atom probe tomography. Our results suggest that the high number density of
      nanoscale alpha-phase precipitates in the beta-phase matrix is due to omega
      assisted nucleation of alpha resulting in high tensile strength, greater than any
      current commercial titanium alloy. Thus hierarchical nanostructured Ti185 serves
      as an excellent candidate for replacing costlier titanium alloys and other
      structural alloys for cost-effective lightweighting applications. 

PMID- 27034110
TI  - Broadband diffusion metasurface based on a single anisotropic element and
      optimized by the Simulated Annealing algorithm.
AB  - We propose a new strategy to design broadband and wide angle diffusion
      metasurfaces. An anisotropic structure which has opposite phases under x- and y
      polarized incidence is employed as the "0" and "1" elements base on the concept
      of coding metamaterial. To obtain a uniform backward scattering under normal
      incidence, Simulated Annealing algorithm is utilized in this paper to calculate
      the optimal layout. The proposed method provides an efficient way to design
      diffusion metasurface with a simple structure, which has been proved by both
      simulations and measurements. 

PMID- 27034111
TI  - Immediate pain relief effect of low level laser therapy for sports injuries:
      Randomized, double-blind placebo clinical trial.
AB  - OBJECTIVES: To determine the immediate pain relief effect of low-level laser
      therapy on sports injuries in athletes and degree of pain relief by the therapy.
      DESIGN: Double-blind, randomized, comparative clinical study. METHODS:
      Participants were 32 college athletes with motion pain at a defined site.
      Participants were randomized into two groups in which the tested or placebo laser
      therapy was administered to determine pain intensity from painful action before
      and after laser irradiation, using the Modified Numerical Rating Scale. The post
      therapeutic Modified Numerical Rating Scale score was subtracted from the pre
      therapeutic Modified Numerical Rating Scale score to determine pain intensity
      difference, and the rate of pain intensity difference to pre-therapeutic Modified
      Numerical Rating Scale was calculated as pain relief rate. RESULTS: Low-level
      laser therapy was effective in 75% of the laser group, whereas it was not
      effective in the placebo group, indicating a significant difference in favor of
      the laser group (p<0.001). Pain relief rate was significantly higher in the laser
      group than in the placebo group (36.94% vs. 8.20%, respectively, p<0.001), with
      the difference in pain relief rate being 28.74%. CONCLUSIONS: Low-level laser
      therapy provided an immediate pain relief effect, reducing pain by 28.74%. It was
      effective for pain relief in 75% of participants.

PMID- 27034113
TI  - Seasonal Abundance, Host Suitability, and Feeding Injury of the Brown Marmorated
      Stink Bug, Halyomorpha halys (Heteroptera: Penatomidae), in Selected Vegetables.
AB  - The invasive brown marmorated stink bug,Halyomorpha halys(Stal) (Heteroptera:
      Penatomidae), is a major pest of agricultural crops in the Mid-Atlantic States.
      Here we report the seasonal abundance, host preference, and injury potential ofH.
      halyson tomato, bell pepper, green bean, sweet corn, eggplant, and okra in a
      small-scale, diversified vegetable farm setting. Life-stage densities, feeding
      injury, and crop phenology were monitored throughout the growing season in each
      crop. Populations consisted of both overwintered adults and F1 progeny and
      encompassed almost two generations over the growing season.H. halyspreferred host
      plants with reproductive structures for feeding and was more abundant and capable
      to reproduce on vegetable crops that had extended periods of fruiting. Sweet
      corn, okra, and bell pepper had significant higher abundances of adults and
      nymphs compared with green bean, eggplant, and tomato. Results showed significant
      differences in the reproductive suitability of the host plants, as evident by the
      relative proportion of nymphal stages to adults. Eggplant, okra, and bell pepper
      were the most suitable host plants for reproduction and development, as evident
      by higher proportions of nymphs, with abundance trends indicating progressive
      development to adult eclosion. Crop loss potential due toH. halysfeeding injury
      varied significantly among vegetable host plants. Sweet corn, okra, bell pepper,
      and tomato were very susceptible and experienced the highest injury rate per
      stink bug. The implications of these findings with respect to sampling and
      management ofH. halysin vegetable production are discussed.

PMID- 27034114
TI  - Residual Acute Toxicity of Some Modern Insecticides Toward Two Mirid Predators of
      Tomato Pests.
AB  - The successful integration of chemical and biological control strategies for crop
      pests depends on a thorough evaluation of the effects of pesticides on the
      natural enemies of pests. A case-by-case review is difficult to achieve because
      of the many combinations of pests, natural enemies, and crops that need to be
      tested. Within this framework, we tested and compared seven insecticides
      representative of four different modes of action (MoAs) groups on closely related
      predators (Miridae): flubendiamide, spirotetramat, metaflumizone, and sulfoxaflor
      onNesidiocoris tenuisReuter and flubendiamide, spiromesifen, indoxacarb, and
      imidacloprid onMacrolophus basicornis(Stal). We follow the standardized
      methodology of the International Organization for Biological Control, a
      sequential testing exposure scheme. The lethal effect of each insecticide was
      evaluated in adults after three days of contact with treated surfaces in the
      laboratory, extended laboratory, and semifield tests (inert substrate, tomato
      leaves, and tomato plant as the treated surface, respectively). Flubendiamide,
      spiromesifen, and spirotetramat were classified as harmless (class 1),
      metaflumizone was slightly harmful (class 2) but persistent, indoxacarb was
      harmless (class 1), and sulfoxaflor and imidacloprid were toxic (class 4) and
      exhibited a long residual activity. Our results suggest similarities in the acute
      toxicities of insecticides from the same MoA group on related species of natural
      enemies.

PMID- 27034112
TI  - Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat
      model of arterial injury.
AB  - OBJECTIVE: Lipid mediators derived from omega-3 polyunsaturated fatty acids such
      as resolvin D1 (RvD1) accelerate the resolution of inflammation and have
      potential as vascular therapeutics. The objective of this study was to evaluate
      local perivascular delivery of RvD1 as a means to attenuate neointimal
      hyperplasia in a rat model of arterial injury. METHODS: Smooth muscle cells were
      harvested from rat aortas to study the effects of RvD1 on rat arterial vascular
      smooth muscle cell responses in vitro, with focus on inflammation, proliferation,
      migration, cytoskeletal changes, and cytotoxicity. The safety and efficacy of
      perivascular delivery of RvD1 through thin biodegradable three-layered
      poly(lactic-co-glycolic acid) wraps or 25% Pluronic F127 gels were studied in a
      rat model of carotid angioplasty. A total of 200 ng of RvD1 was loaded into each
      construct for perivascular delivery after injury. Morphometric and histologic
      analyses were performed 3 and 14 days after injury. RESULTS: RvD1 attenuated rat
      arterial vascular smooth muscle cell inflammatory pathways, proliferation,
      migration, and mitogen-induced cytoskeletal changes in vitro, without evidence of
      cytotoxicity. RvD1-loaded wraps reduced neointimal formation after carotid
      angioplasty by 59% vs no-wrap controls (P = .001) and by 45% vs vehicle-wrap
      controls (P = .002). RvD1-loaded Pluronic gels similarly reduced neointimal
      formation by 49% vs no-gel controls (P = .02) and by 52% vs vehicle-gel controls
      (P = .02). No group was associated with infection, thrombosis, or negative vessel
      remodeling. Wraps were found to be easier to apply than gel constructs. Ki67
      proliferation index was significantly lower in RvD1-loaded wrap-treated arteries
      compared with both no-wrap and vehicle-wrap controls at both 3 and 14 days after
      injury (65% vs no-wrap group and 70% vs vehicle-wrap group at day 3, 49% vs both
      control groups at day 14; P < .05). Similarly, oxidative stress (30% and 29%; P <
      .05) and nuclear factor kappaB activation (42% and 45%; P < .05) were
      significantly lower in the RvD1-loaded wrap group compared with both no-wrap and
      vehicle-wrap controls at 3 days after injury. CONCLUSIONS: Local perivascular
      delivery of RvD1 attenuates formation of neointimal hyperplasia without
      associated toxicity in a rat model of carotid angioplasty. This effect is likely
      due to attenuation of inflammatory pathways as well as decreased arterial smooth
      muscle cell proliferation and migration.

PMID- 27034115
TI  - Effects of the Agglutinins Extracted From Rhizoctonia solani (Cantharellales:
      Ceratobasidiaceae) on Pieris brassicae (Lepidoptera: Pieridae).
AB  - Lectins are widespread proteins found in plants, fungi, bacteria, and
      vertebrates, and they play the critical roles in many physiological functions.
      Two lectin molecules (namely, RSAI and RSAII) were extracted fromRhizoctonia
      solaniKuhn and their effects onPieris brassicaeL. larvae were determined by
      larval survival rate, body mass, nutritional indices, digestive enzyme
      activities, andcaspase-3gene expression. The highest mortality caused by RSA
      treatment was recorded up to 80%, the larval weight decreased to 0.05 g and
      Similarly, RSAs significantly decreased nutritional indices including conversion
      efficiency of ingested food (ECI), conversion efficiency of digested food (ECD),
      approximate digestibility (AD), relative consumption rate (RCR), and relative
      growth rate (RGR) in a dose-dependent manner. Activities of alpha-amylase and
      alpha- and beta-glucosidases significantly decreased in the larvae fed with RSA
      treated diets. Also, activities of TAG-lipase and proteases significantly reduced
      after feeding with different concentrations of RSAs. Gene expression analysis
      ofcaspase-3in control and treated larvae revealed significant increment of its
      expression in the larvae fed with RSAI and RSAII, respectively, 9.52- and 1.47
      fold compared to control. These results clearly demonstrated insecticidal effects
      ofR. solanilectins onP. brassicaevia several physiological pathways, thus
      rendering RSA as a good target for furthering our knowledge and suggesting new
      strategies to overcome pesticide side effects.

PMID- 27034116
TI  - Blood glucose regulation mechanism in depressive disorder animal model during
      hyperglycemic states.
AB  - Depression is more common among diabetes people than in the general population.
      In the present study, blood glucose change in depression animal model was
      characterized by various types of hyperglycemia models such as d-glucose-fed-,
      immobilization stress-, and drug-induced hyperglycemia models. First, the ICR
      mice were enforced into chronic restraint stress for 2h daily for 2 weeks to
      produce depression animal model. The animals were fed with d-glucose (2g/kg),
      forced into restraint stress for 30min, or administered with clonidine
      (5MUg/5MUl) supraspinally or spinally to produce hyperglycemia. The blood glucose
      level in depression group was down-regulated compared to that observed in the
      normal group in d-glucose-fed-, restraint stress-, and clonidine-induced
      hyperglycemia models. The up-regulated corticosterone level induced by d-glucose
      feeding or restraint stress was reduced in the depression group while the up
      regulation of plasma corticosterone level is further elevated after i.t. or
      i.c.v. clonidine administration in the depression group. The up-regulated insulin
      level induced by d-glucose feeding or restraint stress was reduced in the
      depression group. On the other hand, blood corticosterone level in depression
      group was up-regulated compared to the normal group after i.t. or i.c.v.
      clonidine administration. Whereas the insulin level in depression group was not
      altered when mice were administered clonidine i.t. or i.c.v. Our results suggest
      that the blood glucose level in depression group is down-regulated compared to
      the normal group during d-glucose-fed-, immobilization stress-, and clonidine
      induced hyperglycemia in mice. The down-regulation of the blood glucose level
      might be one of the important pathophysiologic changes in depression.

PMID- 27034117
TI  - Memantine ameliorates autistic behavior, biochemistry & blood brain barrier
      impairments in rats.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder, commonly
      characterized by altered social behavior, communication, biochemistry and
      pathological conditions. One percent of the worldwide population suffers from
      autism and males suffer more than females. NMDA receptors have the important role
      in neurodevelopment, neuropsychiatric and neurodegenerative disorders. This study
      has been designed to investigate the role of memantine, a NMDA receptor
      modulator, in prenatal valproic acid-induced autism in rats. Animals with
      prenatal valproic acid have shown the reduction in social interaction (three
      chamber social behavior apparatus), spontaneous alternation (Y-Maze), exploratory
      activity (Hole board test), intestinal motility, serotonin levels (both in
      prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity
      (complex I, II, IV). Furthermore, prenatal valproic acid-treated animals have
      shown an increase in locomotion (actophotometer), anxiety (elevated plus maze),
      brain oxidative stress (thiobarbituric acid reactive species, glutathione,
      catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and
      ileum myeloperoxidase activity), calcium and blood-brain barrier permeability.
      Treatment with memantine has significantly attenuated prenatal valproic acid
      induced reduction in social interaction, spontaneous alteration, exploratory
      activity intestinal motility, serotonin levels and prefrontal cortex
      mitochondrial complex activity. Furthermore, memantine has also attenuated the
      prenatal valproic acid-induced increase in locomotion, anxiety, brain oxidative
      and nitrosative stress, inflammation, calcium and blood-brain barrier
      permeability. Thus, it may be concluded that prenatal valproic acid has induced
      autistic behavior, biochemistry and blood-brain barrier impairment in animals,
      which were significantly attenuated by memantine. NMDA receptor modulators like
      memantine should be explored further for the therapeutic benefits in autism.

PMID- 27034118
TI  - Is the 5-ports approach necessary in laparoscopic gastrectomy? Feasibility of
      reduced-port totally laparoscopic gastrectomy for the treatment of gastric
      cancer: A Prospective Cohort Study.
AB  - BACKGROUND/AIM: Interest of gastric cancer patients in the quality of life
      postoperatively with respect to reduced scarring is increasing. This study aimed
      to evaluate the feasibility of reduced-port totally laparoscopic gastrectomy
      (RepTLG) for the treatment of gastric cancer. METHODS: In total, 170 patients who
      underwent RepTLG (n = 97) or conventional totally laparoscopic gastrectomy (cTLG)
      (n = 73) were enrolled. Clinicopathological features, operative details, and
      short-term postoperative outcomes were analyzed retrospectively and compared
      between groups. RESULTS: There were no significant differences for preoperative
      comorbidity between the RepTLG and c TLG groups, although patients in the RepTLG
      group were older than those in the cTLG group (63.5 +/- 11.1 vs. 59.3 +/- 10.6; p
      = 0.014). Operating time was shorter in the RepTLG group compared to the cTLG
      group (187.5 +/- 67.7 min vs. 219.6 +/- 43.3 min; p < 0.001) and duration of
      flatus of the RepTLG group was shorter than that of the cTLG group (2.7 +/- 0.6
      days vs. 2.9 +/- 0.8 days; p = 0.016). CONCLUSION: RepTLG is a reliable scar
      reducing method with good operative and short-term outcomes for the treatment of
      gastric cancer compared with cTLG.

PMID- 27034119
TI  - Ventricular arrhythmia burst is an independent indicator of larger infarct size
      even in optimal reperfusion in STEMI.
AB  - OBJECTIVE: We hypothesized that ventricular arrhythmia (VA) bursts during
      reperfusion phase are a marker of larger infarct size despite optimal epicardial
      and microvascular perfusion. METHODS: 126 STEMI patients were studied with 24h
      continuous, 12-lead Holter monitoring. Myocardial blush grade (MBG) was
      determined and VA bursts were identified against subject-specific background VA
      rates in core laboratories. Delayed-enhancement cardiovascular magnetic resonance
      imaging was used to determine infarct size. RESULTS: In the group with MBG 3 no
      significant differences were found for baseline characteristics between burst
      versus no burst (102 vs. 24). In those with optimal epicardial and microvascular
      reperfusion (TIMI 3, stable ST-recovery, and MBG 3), VA burst was associated with
      larger infarct size (N=102/126; median 11.0 vs. 5.1%; p=0.004). CONCLUSION: In
      the event of MBG 3, VA bursts were associated with significantly larger infarct
      size even if optimal epicardial and microvascular reperfusion was present.

PMID- 27034120
TI  - QRS broadening due to terminal distortion is associated with the size of
      myocardial injury in experimental myocardial infarction.
AB  - INTRODUCTION: Not only repolarization, but also depolarization ECG indexes
      reflect the progression of ischemic injury. The aim was to assess the QRS
      duration and morphology dynamics during the prolonged coronary occlusion and
      their association with the myocardial area at risk (MaR) and final infarct size
      (IS). METHODS: In pigs, myocardial infarction was induced by inflation of an
      angioplasty balloon in the left descending artery (LAD), and ECG was continuously
      recorded. QRS duration was calculated on a beat-to-beat basis during the
      occlusion period. Single photon emission computed tomography (SPECT) was
      performed for the assessment of MaR, and IS was assessed by magnetic resonance
      imaging (MRI). RESULTS: All animals developed an anteroseptal infarction with MaR
      40+/-9% and IS 23+/-7%. Two peaks of QRS widening were found in all animals: the
      early peak immediately after LAD occlusion and the late one 17.7+/-4.1min later.
      No association was found between MaR and IS and either QRS width or the degree of
      QRS widening at the early peak. QRS duration on the late peak correlated with
      both MaR (r=0.61; p=0.007) and IS (r=0.55; p=0.018). CONCLUSION: The QRS widening
      at the late peak, but not at the early peak, is associated with the size of
      myocardial injury, suggesting different underlying mechanisms.

PMID- 27034121
TI  - Transmural, interventricular, apicobasal and anteroposterior action potential
      duration gradients are all essential to the genesis of the concordant and
      realistic T wave: A whole-heart model study.
AB  - BACKGROUND: It has been reported that ventricular repolarization dispersion
      resulting from transmural, apicobasal and interventricular action potential
      duration (APD) gradients makes the T wave concordant with the QRS complex. METHOD
      AND RESULTS: A whole-heart model integrating transmural, apicobasal,
      interventricular and anteroposterior APD gradients was used, and the
      corresponding electrocardiograms were simulated to study the influence of these
      APD gradients on the T-wave amplitudes. The simulation results showed that
      changing a single APD gradient (e.g., interventricular APD gradient alone) only
      made substantial changes to the T-wave amplitudes in a limited number of leads
      and was not able to generate T waves with amplitudes comparable with clinical
      findings in all leads. A combination of transmural, apicobasal and
      interventricular APD gradients could simulate T waves with amplitudes similar to
      clinical values in the limb leads only. Adding the anteroposterior APD gradient
      into the model greatly improved the consistency between the simulated T-wave
      amplitudes and the clinical values. CONCLUSION: The simulation results support
      that the transmural, apicobasal, interventricular and the anteroposterior APD
      gradient are all essential to the genesis of the clinical T wave.

PMID- 27034122
TI  - The relation between oxidative stress biomarkers and atrial fibrillation after
      pulmonary veins isolation.
AB  - INTRODUCTION: The current paradigm claims a link between oxidative stress and
      atrial fibrillation. The aim of our research was to study a relation between the
      percentage of time spent in atrial fibrillation (AF burden) and concentrations of
      oxidative stress biomarkers, before and after pulmonary veins isolation (PVI).
      METHODOLOGY: We included 19 patients (mean age 55+/-10years, 4 females and 15
      males) with implanted loop recorders undergoing PVI. Plasmatic concentrations of
      advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein
      products and thiobarbituric-acid reacting substances (TBARS) were measured and AF
      burden was recorded immediately before and 3months after the PVI. AF burden was
      also recorded 9months after the PVI. RESULTS: Post procedural AGEs concentration
      significantly negatively correlated with AF burden after 3months (rho=-0.63;
      p<0.01) and 9months (rho=-0.5; p=0.04), respectively as well as TBARS
      concentration significantly negatively correlated with AF burden after 9months
      (rho=-0.61; p=0.01). CONCLUSION: Our study showed AGEs and TBARS to be potential
      predictors for AF burden after the PVI. We suppose that the more oxidative stress
      after the PVI is provoked, the more fibrotic tissue is produced. That means a
      better electrical isolation of pulmonary veins and consequently a lower AF
      burden.

PMID- 27034123
TI  - A fundamental relationship between intraventricular conduction and heart rate.
AB  - BACKGROUND: Existence of a relationship between the electrocardiographic QRS
      interval duration and the diurnally varying heart rate, of consistent sign and
      magnitude, is controversial and the relationship has not been fully characterized
      in normal populations. METHODS AND RESULTS: We analyzed the QRS-RR interval
      relationship in 884 Holter recordings in 410 normal subjects participating in 5
      clinical trials. The slope of the linear regression of QRS on RR was positive in
      93% of subjects with an average slope of 0.0125, which indicates an increase in
      QRS duration of 1.25msec for an increase in RR interval of 100msec. The increase
      was 15% larger in women than in men. Age had no significant effect on the slope.
      CONCLUSIONS: In two populations of normal subjects we observed a robust, direct
      relationship between the spontaneously changing RR interval and intraventricular
      conduction time represented by the duration of the QRS interval. As heart rate
      increases, QRS duration decreases. The change is larger in women. These
      observations have important physiological and clinical implications.

PMID- 27034124
TI  - [Geriatric intervention in elderly hip fracture patients admitted to University
      Hospital of Guadalajara: Clincal, healthcare and economical repercussions].
AB  - OBJECTIVE: To evaluate the healthcare outcomes and economic impact of geriatric
      intervention in patients over 75 years old with hip fracture in acute phase.
      MATERIAL AND METHODS: Retrospective study of patients admitted to the University
      Hospital of Guadalajara (HUGU) due to hip fracture. An analysis was made of the
      number of cases per year, preoperative period, hospital stay, and mortality of
      all the patients over 75 years admitted to the HUGU due to hip fracture between
      2002 and 2013. RESULTS: A total of 2942 patients were included. Comparing the
      activity of 2013 to that of 2006, the mean hospital stay fell from 18.5 to 11.2
      days (-39.2%), and mortality from 8.9% to 6.8% (-23%). In contrast, the mean
      preoperative stay remained at a mean of 2.7 days versus 2.4 in previous years in
      the early post-intervention period. Hospital stay decreased, despite a
      progressive annual increase in the daily cost of hospitalisation due to hip
      fracture surgery, the reduced stay led to a reduction of the total cost by more
      than 900,000 euros each year. Geriatric intervention has gradually reduced mean
      hospital stay and mortality, although with a tendency to increase mean
      preoperative stay. CONCLUSIONS: Geriatric intervention in patients with hip
      fracture reduces mortality and length of hospital stay, and decreasing costs.

PMID- 27034125
TI  - It's not the destination, it's the 'road to load' that matters: a tennis injury
      prevention perspective.

PMID- 27034126
TI  - Role of illness in male professional football: not a major contributor to time
      loss.
AB  - BACKGROUND: There are limited data on the nature, type and incidence of illness
      in football. Previous studies indicate that gastrointestinal and respiratory
      tract illnesses are most common. AIM: To describe the incidence and burden of
      illness in male professional football. METHODS: Over the 4-year study period,
      2011-2014, 73 professional football teams in Europe participated, with a total of
      1 261 367 player-days recorded. All time-loss illnesses were recorded by the
      medical staff of each club. A recordable illness episode was any physical or
      psychological symptom (not related to injury) that resulted in the player being
      unable to participate fully in training or match play. RESULTS: A total of 1914
      illness episodes were recorded. The illness incidence was 1.5 per 1000 player
      days, meaning that, on average, a player experienced an illness episode every
      second season, with a median of 3 days absence per illness episode. Severe
      illness (absence >4 weeks) constituted 2% of all illnesses. Respiratory tract
      illness was the most common (58%), followed by gastrointestinal illness (38%).
      Respiratory tract illness, gastrointestinal illness and cardiovascular illness
      caused the highest illness burden. CONCLUSIONS: The illness incidence among male
      professional football players is low compared with the injury incidence. We found
      that the highest illness burden was caused by illness to the respiratory tract,
      gastrointestinal tract and cardiovascular system.

PMID- 27034127
TI  - Economic impact study: neuromuscular training reduces the burden of injuries and
      costs compared to standard warm-up in youth soccer.
AB  - BACKGROUND: There is randomised controlled trial (RCT) evidence that
      neuromuscular training (NMT) programmes can reduce the risk of injury in youth
      soccer. We evaluated the cost-effectiveness of such an NMT prevention strategy
      compared to a standard of practice warm-up. METHODS: A cost-effectiveness
      analysis was conducted alongside a cluster RCT. Injury incidence rates were
      adjusted for cluster using Poisson regression analyses. Direct healthcare costs
      and injury incidence proportions were adjusted for cluster using bootstrapping.
      The joint uncertainty surrounding the cost and injury rate and proportion
      differences was estimated using bootstrapping with 10 000 replicates. RESULTS:
      Along with a 38% reduction in injury risk (rate difference=-1.27/1000 player
      hours (95% CI -0.33 to -2.2)), healthcare costs were reduced by 43% in the NMT
      group (-$689/1000 player hours (95% CI -$1741 to $234)) compared with the control
      group. 90% of the bootstrapped ratios were in the south-west quadrant of the cost
      effectiveness plane, showing that the NMT programme was dominant (more effective
      and less costly) over standard warm-up. Projecting results onto 58 100 Alberta
      youth soccer players, an estimated 4965 injuries and over $2.7 million in
      healthcare costs would be conservatively avoided in one season with
      implementation of a neuromuscular training prevention programme. CONCLUSIONS:
      Implementation of an NMT prevention programme in youth soccer is effective in
      reducing the burden of injury and leads to considerable reduction in costs. These
      findings inform practice and policy supporting the implementation of NMT
      prevention strategies in youth soccer nationally and internationally.

PMID- 27034128
TI  - Potential limitations of the functional movement screen: a clinical commentary.

PMID- 27034129
TI  - ACL injuries in men's professional football: a 15-year prospective study on time
      trends and return-to-play rates reveals only 65% of players still play at the top
      level 3 years after ACL rupture.
AB  - BACKGROUND: Studies investigating the development of ACL injuries over time in
      football are scarce and more data on what happens before and after return to play
      (RTP) are needed. AIM: To investigate (1) time trends in ACL injury rates, (2)
      complication rates before return to match play following ACL reconstruction, and
      (3) the influence of ACL injury on the subsequent playing career in male
      professional football players. METHODS: 78 clubs were followed between 2001 and
      2015. Time trend in ACL injury rate was analysed using linear regression. ACL
      injured players were monitored until RTP and tracked for 3 years after RTP.
      RESULTS: We recorded 157 ACL injuries, 140 total and 17 partial ruptures, with a
      non-significant average annual increase in the ACL injury rate by 6% (R(2)=0.13,
      b=0.059, 95% CI -0.04 to 0.15, p=0.20). The match ACL injury rate was 20-fold
      higher than the training injury rate (0.340 vs 0.017 per 1000 h). 138 players
      (98.6%) with a total rupture underwent ACL reconstruction; all 134 players with
      RTP data (4 players still under rehabilitation) were able to return to training,
      but 9 of them (6.7%) suffered complications before their first match appearance
      (5 reruptures and 4 other knee surgeries). The median layoff after ACL
      reconstruction was 6.6 months to training and 7.4 months to match play. We report
      3-year follow-up data for 106 players in total; 91 players (85.8%) were still
      playing football and 60 of 93 players (65%) with ACL reconstruction for a total
      rupture played at the same level. CONCLUSIONS: The ACL injury rate has not
      declined during the 2000s and the rerupture rate before return to match play was
      4%. The RTP rate within a year after ACL reconstruction was very high, but only
      two-thirds competed at the highest level 3 years later.

PMID- 27034130
TI  - Acupuncture for sciatica and a comparison with Western Medicine (PEDro
      synthesis).

PMID- 27034132
TI  - ERRATUM.

PMID- 27034131
TI  - Fueling Cancer: Glucose, Again.

PMID- 27034133
TI  - ERRATUM.

PMID- 27034134
TI  - Multiple sclerosis: potential risk factors in childhood and adolescence.

PMID- 27034135
TI  - Impaired mechanical response of an EDMD mutation leads to motility phenotypes
      that are repaired by loss of prenylation.
AB  - There are roughly 14 distinct heritable autosomal dominant diseases associated
      with mutations in lamins A/C, including Emery-Dreifuss muscular dystrophy (EDMD).
      The mechanical model proposes that the lamin mutations change the mechanical
      properties of muscle nuclei, leading to cell death and tissue deterioration.
      Here, we developed an experimental protocol that analyzes the effect of disease
      linked lamin mutations on the response of nuclei to mechanical strain in living
      Caenorhabditis elegans We found that the EDMD mutation L535P disrupts the nuclear
      mechanical response specifically in muscle nuclei. Inhibiting lamin prenylation
      rescued the mechanical response of the EDMD nuclei, reversed the muscle
      phenotypes and led to normal motility. The LINC complex and emerin were also
      required to regulate the mechanical response of C. elegans nuclei. This study
      provides evidence to support the mechanical model and offers a potential future
      therapeutic approach towards curing EDMD.

PMID- 27034136
TI  - A mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid
      disorder.
AB  - In 1994 in the Journal of Cell Science, Hennekes and Nigg reported that changing
      valine to arginine at the endoproteolytic cleavage site in chicken prelamin A
      abolishes its conversion to lamin A. The consequences of this mutation in an
      organism have remained unknown. We now report that the corresponding mutation in
      a human subject leads to accumulation of prelamin A and causes a progeroid
      disorder. Next generation sequencing of the subject and her parents' exomes
      identified a de novo mutation in the lamin A/C gene (LMNA) that resulted in a
      leucine to arginine amino acid substitution at residue 647 in prelamin A. The
      subject's fibroblasts accumulated prelamin A, a farnesylated protein, which led
      to an increased percentage of cultured cells with morphologically abnormal
      nuclei. Treatment with a protein farnesyltransferase inhibitor improved abnormal
      nuclear morphology. This case demonstrates that accumulation of prelamin A,
      independent of the loss of function of ZMPSTE24 metallopeptidase that catalyzes
      processing of prelamin A, can cause a progeroid disorder and that a cell biology
      assay could be used in precision medicine to identify a potential therapy.

PMID- 27034137
TI  - Myosin II governs collective cell migration behaviour downstream of guidance
      receptor signalling.
AB  - Border cell migration during Drosophila oogenesis is a potent model to study
      collective cell migration, a process involved in development and metastasis.
      Border cell clusters adopt two main types of behaviour during migration: linear
      and rotational. However, the molecular mechanism controlling the switch from one
      to the other is unknown. Here, we demonstrate that non-muscle Myosin II (NMII,
      also known as Spaghetti squash) activity controls the linear-to-rotational
      switch. Furthermore, we show that the regulation of NMII takes place downstream
      of guidance receptor signalling and is critical to ensure efficient collective
      migration. This study thus provides new insight into the molecular mechanism
      coordinating the different cell behaviours in a migrating cluster.

PMID- 27034138
TI  - Basolateral sorting and transcytosis define the Cu+-regulated translocation of
      ATP7B to the bile canaliculus.
AB  - The Cu(+) pump ATP7B plays an irreplaceable role in the elimination of excess
      Cu(+) by the hepatocyte into the bile. The trafficking and site of action of
      ATP7B are subjects of controversy. One current proposal is that an increase in
      intracellular Cu(+) results in the translocation of ATP7B to the lysosomes and
      excretion of excess Cu(+) through lysosomal-mediated exocytosis at the bile
      canaliculus. Here, we show that ATP7B is transported from the trans-Golgi network
      (TGN) to the bile canaliculus by basolateral sorting and endocytosis, and
      microtubule-mediated transcytosis through the subapical compartment. Trafficking
      ATP7B is not incorporated into lysosomes, and addition of Cu(+) does not cause
      relocalization of lysosomes and the appearance of lysosome markers in the bile
      canaliculus. Our data reveal the pathway of the Cu(+)-mediated transport of ATP7B
      from the TGN to the bile canaliculus and indicates that the bile canaliculus is
      the primary site of ATP7B action in the elimination of excess Cu(.)

PMID- 27034139
TI  - Cell-cycle-dependent TGFbeta-BMP antagonism regulates neural tube closure by
      modulating tight junctions.
AB  - Many organs form by invaginating and rolling flat epithelial cell sheets into
      tubes. Invagination of the ventral midline of the neural plate forms the median
      hinge point (MHP), an event that elevates the neural folds and is essential for
      neural tube closure (NTC). MHP formation involves dynamic spatiotemporal
      modulations of cell shape, but how these are achieved is not understood. Here, we
      show that cell-cycle-dependent BMP and TGFbeta antagonism elicits MHP formation
      by dynamically regulating interactions between apical (PAR complex) and
      basolateral (LGL) polarity proteins. TGFbeta and BMP-activated receptor (r)-SMADs
      [phosphorylated SMAD2 or SMAD3 (pSMAD2,3), or phosphorylated SMAD1, SMAD5 or
      SMAD8 (pSMAD1,5,8)] undergo cell-cycle-dependent modulations and nucleo-cytosolic
      shuttling along the apicobasal axis of the neural plate. Non-canonical TGFbeta
      and BMP activity in the cytosol determines whether pSMAD2,3 or pSMAD1,5,8
      associates with the tight junction (PAR complex) or with LGL, and whether cell
      shape changes can occur at the MHP. Thus, the interactions of BMP and TGFbeta
      with polarity proteins dynamically modulate MHP formation by regulating r-SMAD
      competition for tight junctions and r-SMAD sequestration by LGL.

PMID- 27034140
TI  - Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for
      Atypical Teratoid/Rhabdoid Tumor.
AB  - PURPOSE: We prospectively evaluated the effectiveness of tandem high-dose
      chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in
      improving the survival of patients with atypical teratoid/rhabdoid tumors while
      reducing the risks of late adverse effects from radiotherapy (RT). MATERIALS AND
      METHODS: For young children (< 3 years old), tandem HDCT/auto-SCT was
      administered after six cycles of induction chemotherapy. RT was deferred until
      after 3 years of age unless the tumor showed relapse or progression. For older
      patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6
      Gy) was administered either after two cycles of induction chemotherapy or after
      surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction
      chemotherapy. RESULTS: A total of 13 patients (five young and eight older) were
      enrolled from November 2004 to June 2012. Eight patients, including all five
      young patients, had metastatic disease at diagnosis. Six patients (four young and
      two older) experienced progression before initiation of RT, and seven were able
      to proceed to HDCT/auto-SCT without progression during induction treatment. Three
      of six patients who experienced progression during induction treatment underwent
      HDCT/auto-SCT as salvage treatment. All five young patients died from disease
      progression. However, four of the eight older patients remain progression
      freewith a median follow-up period of 64 months (range, 39 to 108 months).
      Treatment-related late toxicities were acceptable. CONCLUSION: The required dose
      of craniospinal RT might be reduced in older patients if the intensity of
      chemotherapy is increased. However, early administration of RT should be
      considered to prevent early progression in young patients.

PMID- 27034141
TI  - Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine,
      Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment
      with Defibrotide.
AB  - Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that
      generally occurs as a complication after hematopoietic stem cell transplantation
      or, less commonly, after conventional chemotherapy. Regarding SOS in
      rhabdomyosarcoma patients who received conventional chemotherapy, the doses of
      chemotherapeutic agents are associated with the development of SOS. Several cases
      of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated
      doses of cyclophosphamide have been reported. Here, we report on a 9-year-old
      female with rhabdomyosarcoma who developed severe SOS after receiving
      chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of
      cyclophosphamide. She was treated successfully with defibrotide without sequelae
      to the liver.

PMID- 27034142
TI  - A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating
      Tumor Cells in Patients with Liver Cancer.
AB  - PURPOSE: We developed a new method of detecting circulating tumor cells (CTCs) in
      liver cancer patients by constructing cell blocks from peripheral blood cells,
      including CTCs, followed by multiple immunohistochemical analysis. MATERIALS AND
      METHODS: Cell blockswere constructed from the nucleated cell pellets of
      peripheral blood afterremoval of red blood cells. The blood cell blocks were
      obtained from 29 patients with liver cancer, and from healthy donor blood
      spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were
      immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell
      adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, alpha
      fetoprotein (AFP), Glypican 3, and HepPar1. RESULTS: The average recovery rate of
      spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out
      of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2
      cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs
      from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18
      (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC
      expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1,
      and Glypican3 were expressed only in tissue. Only EMA was significantly
      associated with the expressions in CTC and tissue. CTC detection was associated
      with higher T stage and portal vein invasion in HCC patients. CONCLUSION: This
      cell block method allows cytologic detection and multiple immunohistochemical
      analysis of CTCs. Our results show that tissue biomarkers of HCC may not be
      useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in
      patients with HCC.

PMID- 27034143
TI  - Prediction of Cancer Incidence and Mortality in Korea, 2016.
AB  - PURPOSE: To estimate of Korea's current cancer burden, this study aimed to report
      on projected cancer incidence and mortality rates for the year 2016. MATERIALS
      AND METHODS: Cancer incidence data from 1999 to 2013 were obtained from the Korea
      National Cancer Incidence Database, and cancer mortality data from 1993 to 2014
      were acquired from Statistics Korea. Cancer incidence in 2016 was projected by
      fitting a linear regression model to observed age-specific cancer incidence rates
      against observed years, then multiplying the projected age-specific rates by the
      age-specific population. The Joinpoint regression model was used to determine at
      which year the linear trend changed significantly. RESULTS: A total of 254,962
      new cancer cases and 75,172 cancer deaths are expected to occur in Korea in 2016.
      The five leading primary cancer incident sites in 2016 were estimated colorectal,
      stomach, lung, liver and thyroid cancer in men; thyroid, breast, colorectal,
      stomach, and lung cancer in women. CONCLUSION: Currently cancer is one of the
      foremost public health concerns in Korea. Although cancer rates are anticipated
      to decrease the nation's cancer burden will continue to increase as the
      population ages.

PMID- 27034144
TI  - Coexistence of VHL Disease and CPT2 Deficiency: A Case Report.
AB  - von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign
      and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2)
      is a disorder of lipid metabolism that, in the muscle form, manifests with
      recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic
      episodes may be complicated by life-threatening events, including acute renal
      failure (ARF). We report on a male patient who was tested, at 10 years of age,
      for VHL disease because of family history of VHL. He was diagnosed with VHL but
      without VHL-related manifestation at the time of diagnosis. During childhood, the
      patient was hospitalized several times for diffuse muscular pain, muscle
      weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never
      accompanied by ARF. The patient was found to be homozygous for the mutation
      p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report
      of the coexistence of VHL disease and CPT2 deficiency in the same individual.
      Based on findings from animal models, the case illustrates that mutations in the
      VHL gene might protect against renal damage caused by CPT2 gene mutations.

PMID- 27034145
TI  - Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral
      Blood at Diagnosis in Patients with Neuroblastoma.
AB  - PURPOSE: The purpose of this study is to investigate the clinical significance of
      tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in
      patients with neuroblastoma. MATERIALS AND METHODS: TH mRNA expression in PB was
      measured by reverse transcription quantitative real-time polymerase chain
      reaction in 210 patients who were newly diagnosed with neuroblastoma from July
      2005 to June 2015 and the clinical significance of TH expression in PB at
      diagnosis was evaluated. RESULTS: TH expression was positive in 60 patients
      (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining
      10 had localized tumors. TH expression was associated with high-risk features
      (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification)
      at diagnosis. Among TH-positive patients, higher TH expression level was observed
      in high-risk patients than in low- or intermediate-risk patients (p=0.035). The
      probability of 5-year progression-free survival (PFS) was lower in TH-positive
      patients than in TH-negative patients (63.8+/-6.9% vs. 94.7+/-2.1%, p < 0.001).
      In analysis confined to high-risk patients, the 5-year probability of PFS
      remained lower in TH-positive patients (55.7+/-8.2% vs. 89.6+/-5.8%, p < 0.001).
      Among TH-positive patients, a higher expression level of TH was associated with a
      worse outcome. In multivariate analyses, positive TH expression in PB at
      diagnosis was an independent poor prognostic factor for PFS. CONCLUSION: The
      treatment intensity should be tailored according to TH expression in PB at
      diagnosis.

PMID- 27034146
TI  - Poor Preoperative Glycemic Control Is Associated with Dismal Prognosis after
      Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Korean
      Multicenter Study.
AB  - PURPOSE: The purpose of this study is to evaluate the effect of diabetes mellitus
      (DM) and preoperative glycemic control on prognosis in Korean patients with upper
      tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU).
      MATERIALS AND METHODS: A total of 566 patients who underwent RNU at six
      institutions between 2004 and 2014 were reviewed retrospectively. Kaplan-Meier
      and Cox regression analyses were performed to assess the association between DM,
      preoperative glycemic control, and recurrence-free, cancer-specific, and overall
      survival. RESULTS: The median follow-up period was 33.8 months (interquartile
      range, 41.4 months). A total of 135 patients (23.8%) had DM and 67 patients
      (11.8%) had poor preoperative glycemic control. Patients with poor preoperative
      glycemic control had significantly shorter median recurrence-free, cancer
      specific, and overall survival than patients with good preoperative glycemic
      control and non-diabetics (all, p=0.001). In multivariable Cox regression
      analysis, DM with poor preoperative glycemic control showed association with
      worse recurrence-free survival (hazard ratio [HR], 2.26; 95% confidence interval
      [CI], 1.31 to 3.90; p=0.003), cancer-specific survival (HR, 2.96; 95% CI, 1.80 to
      4.87; p=0.001), and overall survival (HR, 2.13; 95% CI, 1.40 to 3.22; p=0.001).
      CONCLUSION: Diabetic UTUC patients with poor preoperative glycemic control had
      significantly worse oncologic outcomes than diabetic UTUC patients with good
      preoperative glycemic control and non-diabetics. Further investigation is needed
      to elucidate the exact mechanism underlying the impact of glycemic control on
      UTUC treatment outcome.

PMID- 27034147
TI  - Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of
      Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A
      Multicenter Retrospective Cohort Study.
AB  - PURPOSE: The purpose of this study is to investigate the prognostic value of
      lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant
      chemotherapy. MATERIALS AND METHODS: This retrospective analysis is based on the
      data of 814 patientswith stage II/III breast cancer treated with four cycles of
      doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery.
      We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs.
      intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression
      model. RESULTS: A total of 799 patients underwent breast surgery. Pathologic
      complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone
      receptor [HR] +/human epidermal growth factor receptor 2 [HER2] -, 34/373 [9.1%];
      HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean
      numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98
      (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%];
      intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed
      significant association with a worse relapse-free survival (3-year relapse-free
      survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p <
      0.001, log-rank test). In multivariate analysis, LNR did not show significant
      association with recurrence after adjusting for other clinical factors (age,
      histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion,
      and pCR). In subgroup analysis, the LNR system had good prognostic value in
      HR+/HER2-subtype. CONCLUSION: LNR is not superior to ypN stage in predicting
      clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the
      prognostic value of the LNR system in HR+/HER2-patients is notable and worthy of
      further investigation.

PMID- 27034148
TI  - Prognostic Factors for Risk Stratification of Patients with Recurrent or
      Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based
      Chemotherapy.
AB  - PURPOSE: The aim of this study was to verify prognostic factors including
      sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving
      gemcitabine-based chemotherapy. MATERIALS AND METHODS: Medical records and
      computed tomography scan of consecutive patients treated with palliative
      gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar
      skeletal muscle index at third lumbar spine level was computed, and together with
      clinicolaboratory factors, univariate and multivariable analyses for overall
      survival (OS) were performed. RESULTS: A total of 88 patients were found. Median
      age was 65 years, and male patients were predominant (67.0%). Most patients had
      initially metastatic disease (72.7%), and gemcitabine monotherapy was
      administered in 29 patients (33.0%) while gemcitabine plus erlotinib was
      administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia.
      With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median
      OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate
      and multivariable analysis, high carcinoembryonic antigen level (hazard ratio
      [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR,
      3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36;
      p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high
      lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were
      identified as independent prognostic factors for OS. CONCLUSION: Five independent
      prognostic factors in patients with recurrent or metastatic pancreatic cancer who
      received gemcitabine-based chemotherapy were identified. These findings may be
      helpful in prediction of prognosis in clinical practice and can be used as a
      stratification factor for clinical trials.

PMID- 27034150
TI  - Water assisted colonoscopy: A promising new technique.

PMID- 27034149
TI  - Application of the Chinese Version of the Whiteley Index-7 for Detecting DSM-5
      Somatic Symptom and Related Disorders.
AB  - BACKGROUND: The Whiteley Index-7 (WI-7) is frequently used for evaluating
      patients with suspected hypochondriasis. However, information about its use on
      somatic symptom and related disorders in the Diagnostic and Statistical Manual of
      Mental Disorders, Fifth Edition (DSM-5) is still lacking. This study investigated
      the psychometric properties of the Mandarin Chinese version of the WI-7 and its
      application to evaluation of somatic symptom and related disorders. METHODS:
      Participants completed the WI-7 and received diagnostic interview based on both
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      and DSM-5 criteria. Exploratory factor analysis was performed, and the test
      retest reliability and the internal consistency of the WI-7 were assessed.
      Receiver Operating Characteristic curves were established, and the area under the
      curve was calculated to determine the cutoff point to distinguish DSM-IV
      somatoform disorders and DSM-5 somatic symptom and related disorders,
      respectively. RESULTS: A total of 471 subjects were recruited for this study. The
      exploratory factor analysis of the WI-7 identified a single factor. The internal
      consistency and test-retest reliability of the WI-7 were 0.829 and 0.836,
      respectively. The area under Receiver Operating Characteristic curve using WI-7
      to distinguish DSM-5 somatic symptom and related disorders is 0.660, higher than
      that when applying to distinguish DSM-IV somatoform disorders. The sensitivity
      and specificity at an optimal cutoff point of 0/1 are 0.645 and 0.675,
      respectively. CONCLUSION: The Mandarin Chinese version of the WI-7 is a
      potentially useful tool to detect individuals with DSM-5 somatic symptom and
      related disorders.

PMID- 27034152
TI  - Intraoperative assessment of ossicular fixation.
AB  - Determining the degree of ossicular fixation is a difficult task, with the final
      assessment often being made with manual palpation during exploratory tympanotomy.
      A more objective method to evaluate ossicular fixation would be valuable. In this
      paper we describe a new method which makes use of a magnet and coil to measure
      ossicular motion through the ear canal with an elevated tympanic membrane. We
      report measurements of the vibration response at the umbo, the tip of the incus
      long process and the lateral posterior crus of the stapes before and after
      artificially fixing the stapes footplate and anterior mallear ligament with
      luting cement. Results were obtained on temporal bones, but the practicality of
      the method allows easy clinical implementation. Velocity ratios between different
      measurement points along the ossicular chain may provide a quantitative
      indication of the degree of stapes fixation. Isolated anterior mallear ligament
      fixation was not distinguishable from the unfixed condition.

PMID- 27034151
TI  - Predegenerated Schwann cells--a novel prospect for cell therapy for glaucoma:
      neuroprotection, neuroregeneration and neuroplasticity.
AB  - Glaucoma is an optic neuropathy that leads to irreversible blindness. Because the
      current therapies are not sufficient to protect against glaucoma-induced visual
      impairment, new treatment approaches are necessary to prevent disease
      progression. Cell transplantation techniques are currently considered to be among
      the most promising opportunities for nervous system damage treatment. The
      beneficial effects of undifferentiated cells have been investigated in
      experimental models of glaucoma, however experiments were accompanied by various
      barriers, which would make putative treatment difficult or even impossible to
      apply in a clinical setting. The novel therapy proposed in our study creates
      conditions to eliminate some of the identified barriers described for precursor
      cells transplantation and allows us to observe direct neuroprotective and pro
      regenerative effects in ongoing optic neuropathy without additional modifications
      to the transplanted cells. We demonstrated that the proposed novel Schwann cell
      therapy might be promising, effective and easy to apply, and is safer than the
      alternative cell therapies for the treatment of glaucoma. 

PMID- 27034153
TI  - Acute Kidney Injury and the Risk of Mortality in Children Undergoing
      Hematopoietic Stem Cell Transplantation.
AB  - Acute kidney injury (AKI) is a well-documented complication of pediatric
      hematopoietic stem cell transplantation (HSCT). Dialysis after HSCT is associated
      with a lower overall survival (OS); however, the association between less severe
      AKI and OS is unclear. We retrospectively studied 205 consecutive pediatric HSCT
      patients to determine the incidence and impact of all stages of AKI on OS in
      pediatric HSCT recipients. We used the peak pRIFLE grade during the first 100
      days to classify AKI (ie, R = risk, I = injury, F = failure, L = loss of
      function, E = end-stage renal disease) and used the modified Schwartz formula to
      estimate glomerular filtration rate. AKI was observed in 173 of 205 patients
      (84%). The 1-year OS rate decreased significantly with an increasing severity of
      pRIFLE grades (P < .01). There was no difference in the OS between patients
      without AKI and the R/I group. Regardless of the dialysis status, stages F/L/E
      had significantly lower rates of OS compared with patients without AKI or R/I (P
      < .01). There was no difference in OS among patients with dialysis and F/L/E
      without dialysis (P = .65). Stages F/L/E predicted mortality independent of acute
      graft-versus-host disease, gender, and malignancy. The OS of children after HSCT
      decreases significantly with an increasing severity of AKI within the first 100
      days post-transplant. Although our data did not show an increased risk of
      mortality with stages R/I, stages F/L/E predicted mortality regardless of
      dialysis. Prevention and minimization of AKI may improve survival after pediatric
      HSCT.

PMID- 27034154
TI  - Transcatheter closure through transapical access for mitral paravalvular leak
      after previous trans-septal mitral operation.
AB  - Because paravalvular leak after mitral valve replacement in highly morbid
      patients is a troublesome issue, there has been a growing interest in less
      invasive procedures. We conducted transcatheter paravalvular leak closure of a
      mitral valve prosthesis through left ventricular apical access. The patient had
      undergone redo mitral valve replacement through a transatrial septal approach 2
      months prior to the procedure; thus, penetration of the atrial septum was
      considered to be difficult through the ordinary antegrade trans-septal approach.
      Transapical access for the mitral paravalvular leak was conducted using two
      AMPLATZER Vascular Plugs (St. Jude Medical, St. Paul, MN), with a route directed
      straight to the defect. This approach is an alternative technique for
      transcatheter paravalvular leak closure. This is the first case report of
      transapical access for transcatheter paravalvular leak closure in Japan.

PMID- 27034155
TI  - Electro-stimulated microbial factory for value added product synthesis.
AB  - Interplay of charge between bacteria and electrode has led to emergence of
      bioelectrochemical systems which leads to applications such as production of
      electricity, wastewater treatment, bioremediation and production of value added
      products. Many electroactive bacteria have been identified that have unique
      external electron transport systems. Coupling of electron transport with carbon
      metabolism has opened a new approach of carbon dioxide sequestration. The
      electron transport mechanism involves various cellular and sub cellular
      molecules. The outer membrane cytochromes, Mtr-complex and Ech-complex are few
      key molecules involved in electron transport in many electrogenic bacteria. Few
      cytochrome independent acetogenic electroactive bacteria were also discovered
      using Rnf complex to transport electrons. For improved productivity, an efficient
      bioreactor design is mandatory. It should encompass all certain critical issues
      such as microbial cell retention, charge dissipation, separators and simultaneous
      product recovery. 

PMID- 27034156
TI  - Recovery opportunities for metals and energy from sewage sludges.
AB  - Limitations on current wastewater treatment plant (WWTP) biological processes and
      solids disposal options present opportunities to implement novel technologies
      that convert WWTPs into resource recovery facilities. This review considered
      replacing or augmenting extensive dewatering, anaerobic digestion, and off-site
      disposal with new thermo-chemical and liquid extraction processes. These
      technologies may better recover energy and metals while inactivating pathogens
      and destroying organic pollutants. Because limited direct comparisons between
      different sludge types exist in the literature for hydrothermal liquefaction,
      this study augments the findings with experimental data. These experiments
      demonstrated 50% reduction in sludge mass, with 30% of liquefaction products
      converted to bio-oil and most metals sequestered within a small mass of solid bio
      char residue. Finally, each technology's contribution to the three sustainability
      pillars is investigated. Although limiting hazardous materials reintroduction to
      the environment may increase economic cost of sludge treatment, it is balanced by
      cleaner environment and valuable resource benefits for society. 

PMID- 27034157
TI  - Characterization and ciprofloxacin adsorption properties of activated carbons
      prepared from biomass wastes by H3PO4 activation.
AB  - As biomass wastes, Arundo donax Linn and pomelo peel were used as precursors for
      activated carbons (ALAC and PPAC) preparation by phosphoric acid activation. The
      pore structure and surface acidic functional groups of both carbons were
      characterized by nitrogen adsorption/desorption experiment, NH3-temperature
      programmed desorption (NH3-TPD) and Fourier transform infrared spectroscopy
      (FTIR). A batch of experiments was carried out to investigate the adsorption
      performances of ciprofloxacin under different conditions. Results showed that
      PPAC exhibited larger surface area (1252m(2)/g) and larger portion of mesoporous,
      while ALAC was typical of microporous materials. Results from NH3-TPD suggested
      that ALAC was characteristic of more acidic functional group than PPAC. The
      maximum monolayer adsorption capability was 244mg/g for ALAC and 400mg/L for
      PPAC. Kinetics studies showed intra-particle diffusion was not the unique rate
      controlling step. Boundary layer resistance existed between adsorbent and
      adsorbate. 

PMID- 27034158
TI  - Macroscopic technique for the evaluation of oral tongue tumour thickness: a
      reliable intraoperative method.
AB  - There is no reliable method to assess tumour thickness preoperatively or
      intraoperatively in cases of oral tongue squamous cell carcinoma (SCC). The
      purpose of this study was to evaluate the efficacy of a macroscopic technique to
      measure tumour thickness. This was a prospective study of 51 consecutive patients
      with T1/T2 primary SCC of the oral tongue. All patients underwent primary
      resection with ipsilateral neck dissection. Thickness measurements were obtained
      using Vernier calipers on the fresh specimen. The technique was correlated with
      the microscopic evaluation statistically using (1) Pearson's correlation
      coefficient, (2) intra-class correlation, and (3) Bland-Altman plot with 95%
      confidence intervals. On comparing the macroscopic technique to the microscopic
      evaluation, Pearson's correlation (r) was 0.915 (P<0.001). The inter-rater
      reliability using the intra-class correlation coefficient was 0.955. The Bland
      Altman plot to test the agreement between the techniques showed the average
      difference between macroscopic thickness and microscopic thickness (bias) to be 
      0.421, with 95% limits of agreement of -3.166 and 2.82. There was a significant
      correlation and agreement between the macroscopic and microscopic measures of
      tumour thickness. The macroscopic technique could be used as a reliable tool to
      measure tumour thickness intraoperatively, prior to neck dissection. 

PMID- 27034159
TI  - Exposure to Gambling Advertisements and Gambling Behavior in Young People.
AB  - A cross-sectional survey of 4617 adolescents and young adults from 38 schools in
      two German states was conducted in 2014 to assess the association between
      gambling advertisements and gambling behavior. Exposure to ten gambling
      advertisements was measured with masked ad images; students indicated contact
      frequency and brand recall. Main outcomes were several gambling behaviors
      including probable pathological gambling assessed with the South Oaks Gambling
      Screen (SOGS >= 5). A total of 65.4 % of the students reported gambling at least
      once in their life; 42.2 % gambled in the last 12 months; 6.9 % gambled in the
      last week, and 2.8 % reported probable pathological gambling. The average
      frequency that one of the selected ads had been seen at least once was 29.5 %,
      the average brand recall rate was 9.4 %. After adjustment for confounding,
      multilevel mixed-effects logistic regressions revealed that high gambling ad
      exposure was positively related to all assessed gambling outcomes, with the
      strongest association for weekly gambling. Future studies need to clarify the
      temporal sequence and specificity of these associations.

PMID- 27034160
TI  - Netrin-1 suppresses the MEK/ERK pathway and ITGB4 in pancreatic cancer.
AB  - The axon guidance factor netrin-1 promotes tumorigenesis in multiple types of
      cancers, particularly at their advanced stages. Here, we investigate whether
      netrin-1 is involved in the in vivo growth of pancreatic adenocarcinoma. We show
      that netrin-1 is significantly under-expressed in stage-I/II pancreatic ductal
      adenocarcinoma (PDAC). Netrin-1 over-expression effectively arrests the growth of
      xenografted PDAC cells without decreasing cell proliferation or increasing
      apoptosis in two-dimensional cultures in vitro. Integrin-beta4 (ITGB4) expression
      is significantly reduced, and ITGB4-knockdown mimics the tumor-suppressive effect
      of netrin-1, implying that ITGB4 is a main target of netrin-1 in constraining
      PDAC. We further show that netrin-1 signals to UNC5B/FAK to stimulate nitric
      oxide production, which promotes PP2A-mediated inhibition of the MEK/ERK pathway
      and decreases phosphorylated-c-Jun recruitment to the ITGB4 promoter. Our
      findings suggest that netrin-1 can suppress the growth of PDAC and provide a
      mechanistic insight into this suppression. 

PMID- 27034161
TI  - Genetic and epigenetic factors affect RET gene expression in breast cancer cell
      lines and influence survival in patients.
AB  - Germline and somatic mutations play a crucial role in breast cancer (BC), driving
      the initiation, progression, response to therapy and outcome of the disease.
      Hormonal therapy is limited to patients with tumors expressing steroid hormone
      receptors, such as estrogen receptor (ER), nevertheless resistance often limits
      its success.The RET gene is known to be involved in neurocristopathies such as
      Hirschsprung disease and Multiple Endocrine Neoplasia type 2, in the presence of
      loss-of-function and gain-of-function mutations, respectively. More recently, RET
      over-expression has emerged as a new player in ER-positive (ER+) BC, and as a
      potential target to enhance sensitivity and avoid resistance to tamoxifen
      therapy.Therefore, targeting the RET pathway may lead to new therapies in ER+ BC.
      To this end, we have investigated the molecular mechanisms which underlie RET
      overexpression and its possible modulation in two BC cell lines, MCF7 and T47D,
      showing different RET expression levels. Moreover, we have carried out a pilot
      association study in 93 ER+ BC patients. Consistent with the adverse role of RET
      over-expression in BC, increased overall survival was observed in carriers of the
      variant allele of SNP rs2435357, a RET polymorphism already known to be
      associated with reduced RET expression. 

PMID- 27034162
TI  - FOXM1 promotes invasion and migration of colorectal cancer cells partially
      dependent on HSPA5 transactivation.
AB  - In this study, to investigate whether endoplastic reticulum (ER) stress
      correlated with FOXM1 in colorectal cancer, we analysed the mRNA levels of FOXM1
      and ER stress markers HSPA5 and spliced XBP1 by qRT-PCR. FOXM1 mRNA levels were
      found to positively correlate with HSPA5 in colorectal cancer. However, no
      significant correlation between FOXM1 and spliced XBP1 mRNA levels was found.
      Theses results suggested the positive correlation between FOXM1 and HSPA5 in
      colorectal cancer was not associated with ER stress. Next, we provided evidences
      that FOXM1 promoted HSPA5 transcription by directly binding to and stimulating
      HSPA5 promoter. Moreover, a FOXM1-binding site mapped between -1019 and -1012 bp
      of the proximal HSPA5 promoter was identified. In addition, we found that
      enhancement of cell migration and invasion by FOXM1 was significantly attenuated
      by depletion of HSPA5 in colorectal cancer cell. Furthermore, FOXM1 triggered
      colorectal cancer cell migration and invasion was involved in activities of cell
      surface HSPA5. Lastly, our results suggested FOXM1 facilitated the activities and
      expressions of MMP2 and 9 associated with cell-surface HSPA5 in colorectal cancer
      cells. Moreover, statistically significant positive correlations between FOXM1
      and MMP2 mRNA expression, between HSPA5 and MMP2 were found in colorectal cancer
      tissue specimens. Together, our results suggested that FOXM1-HSPA5 signaling
      might be considered as a novel molecular target for designing novel therapeutic
      regimen to control colorectal cancer metastasis and progression. 

PMID- 27034163
TI  - Cancer therapies activate RIG-I-like receptor pathway through endogenous non
      coding RNAs.
AB  - Emerging evidence indicates that ionizing radiation (IR) and chemotherapy
      activate Type I interferon (IFN) signaling in tumor and host cells. However, the
      mechanism of induction is poorly understood. We identified a novel
      radioprotective role for the DEXH box RNA helicase LGP2 (DHX58) through its
      suppression of IR-induced cytotoxic IFN-beta [1]. LGP2 inhibits activation of the
      RIG-I-like receptor (RLR) pathway upon binding of viral RNA to the cytoplasmic
      sensors RIG-I (DDX58) and MDA5 (IFIH1) and subsequent IFN signaling via the
      mitochondrial adaptor protein MAVS (IPS1). Here we show that MAVS is necessary
      for IFN-beta induction and interferon-stimulated gene expression in the response
      to IR. Suppression of MAVS conferred radioresistance in normal and cancer cells.
      Germline deletion of RIG-I, but not MDA5, protected mice from death following
      total body irradiation, while deletion of LGP2 accelerated the death of
      irradiated animals. In human tumors depletion of RIG-I conferred resistance to IR
      and different classes of chemotherapy drugs. Mechanistically, IR stimulated the
      binding of cytoplasmic RIG-I with small endogenous non-coding RNAs (sncRNAs),
      which triggered IFN-beta activity. We demonstrate that the small nuclear RNAs U1
      and U2 translocate to the cytoplasm after IR treatment, thus stimulating the
      formation of RIG-I: RNA complexes and initiating downstream signaling events.
      Taken together, these findings suggest that the physiologic responses to radio
      /chemo-therapy converge on an antiviral program in recruitment of the RLR pathway
      by a sncRNA-dependent activation of RIG-I which commences cytotoxic IFN
      signaling. Importantly, activation of interferon genes by radiation or
      chemotherapy is associated with a favorable outcome in patients undergoing
      treatment for cancer. To our knowledge, this is the first demonstration of a cell
      intrinsic response to clinically relevant genotoxic treatments mediated by an RNA
      dependent mechanism. 

PMID- 27034164
TI  - Neuroendocrine-like cells -derived CXCL10 and CXCL11 induce the infiltration of
      tumor-associated macrophage leading to the poor prognosis of colorectal cancer.
AB  - Our previous study revealed that neuroendocrine differentiation in colorectal
      cancer is one of the important factors leading to worse prognosis. In this study,
      we apply immunohistochemical staining, Western-blot, RT-PCR and ELISA to
      investigate the underlying mechanism that how the neuroendocrine differentiation
      to affect the prognosis of colorectal cancer. The interaction of colorectal
      cancer cells, neuroendocrine-like cells and tumor-associated macrophages in
      colorectal cancer progress is also investigated. By analyzing 82 cases of
      colorectal cancer patients treated in our institution, we found that colorectal
      adenocarcinoma with neuroendocrine differentiation had increasing number of tumor
      associated macrophages and worse prognosis. Further evaluation of cytology showed
      that neuroendocrine cells have the ability to recruit tumor-associated
      macrophages to infiltrate the tumor tissue, and the tumor-associated macrophages
      enhance the proliferation and invasion abilities of the colon cancer cells.
      Moreover, we confirmed that CXCL10 and CXCL11 are the key chemokines in
      neuroendocrine-like cells and they promote the chemotaxis activity of tumor
      associated macrophages. The secretion of CXCL10 and CXCL11 by neuroendocrine-like
      cells can recruit tumor-associated macrophages to infiltrate in tumor tissues.
      The latter enhances the proliferation and invasion of colorectal cancer cell and
      lead to poor prognosis. 

PMID- 27034165
TI  - Spatial memory impairment by TRPC1 depletion is ameliorated by environmental
      enrichment.
AB  - Canonical transient receptor potential (TRPC) channels are widely expressed
      throughout the nervous system whereas their functions remain largely unclear.
      Here we investigated the effects of TRPC1 deletion on spatial memory ability of
      mice and the potential intervention by environmental enrichment (EE). Significant
      spatial memory impairment assessed by conditional fearing test, Y maze test and
      step-down test in TRPC1 knockout mice was revealed. The behavioral abnormality
      were attenuated by the treatment of EE. Proteomic analysis by two-dimensional
      fluorescence difference gel electrophoresis (2D-DIGE) coupled with a matrix
      assisted laser desorption/ionisation-time of flight (MALDI-TOF) and tandem mass
      spectrometry (MS) revealed that TRPC1 deletion caused differential expression of
      a total of 10 proteins (8 up-regulated and 2 down-regulated) in hippocampus. EE
      treatment resulted in differential expression of a total of 22 proteins (2 up
      regulated and 20 down-regulated) in hippocampus of TRPC1 knockout mice. Among
      these differentially expressed proteins, the expression of alpha-internexin and
      glia maturation factor beta (GMF-beta), two proteins shown to impair memory, were
      significantly down-regulated in hippocampus of TRPC1 knockout mice by EE
      treatment. Taken together, these data suggested that TRPC1 regulated directly or
      indirectly the expression of multiple proteins, which may be crucial for the
      maintenance of memory ability, and that EE treatment modulated spatial memory
      impairment caused by TRPC1 depletion and the mechanisms may involve the
      modulation of EE on the expression of those dys-regulated proteins such as alpha
      internexin and GMF-beta in hippocampus. 

PMID- 27034166
TI  - Mutational analysis of single circulating tumor cells by next generation
      sequencing in metastatic breast cancer.
AB  - Circulating Tumor Cells (CTCs) represent a "liquid biopsy" of the tumor
      potentially allowing real-time monitoring of cancer biology and therapies in
      individual patients.The purpose of the study was to explore the applicability of
      a protocol for the molecular characterization of single CTCs by Next Generation
      Sequencing (NGS) in order to investigate cell heterogeneity and provide a tool
      for a personalized medicine approach.CTCs were enriched and enumerated by
      CellSearch in blood from four metastatic breast cancer patients and singularly
      isolated by DEPArray. Upon whole genome amplification 3-5 single CTCs per patient
      were analyzed by NGS for 50 cancer-related genes.We found 51 sequence variants in
      25 genes. We observed inter- and intra-patient heterogeneity in the mutational
      status of CTCs.The highest number of somatic deleterious mutations was found in
      the gene TP53, whose mutation is associated with adverse prognosis in breast
      cancer.The discordance between the mutational status of the primary tumor and
      CTCs observed in 3 patients suggests that, in advanced stages of cancer, CTC
      characteristics are more closely linked to the dynamic modifications of the
      disease status.In one patient the mutational profiles of CTCs before and during
      treatment shared only few sequence variants.This study supports the applicability
      of a non-invasive approach based on the liquid biopsy in metastatic breast cancer
      patients which, in perspective, should allow investigating the clonal evolution
      of the tumor for the development of new therapeutic strategies in precision
      medicine. 

PMID- 27034167
TI  - REST reduction is essential for hypoxia-induced neuroendocrine differentiation of
      prostate cancer cells by activating autophagy signaling.
AB  - Prostate cancer (PCa) with neuroendocrine differentiation (NED) is tightly
      associated with hormone refractory PCa (HRPC), an aggressive form of cancer that
      is nearly impossible to treat. Determining the mechanism of the development of
      NED may yield novel therapeutic strategies for HRPC. Here, we first demonstrate
      that repressor element-1 silencing transcription factor (REST), a transcriptional
      repressor of neuronal genes that has been implicated in androgen-deprivation and
      IL-6 induced NED, is essential for hypoxia-induced NED of PCa cells.
      Bioinformatics analysis of transcriptome profiles of REST knockdown during
      hypoxia treatment demonstrated that REST is a master regulator of hypoxia-induced
      genes. Gene set enrichment analysis (GSEA) of hypoxia and REST knockdown co
      upregulated genes revealed their correlation with HRPC. Consistently, gene
      ontology (GO) analysis showed that REST reduction potential associated with
      hypoxia-induced tumorigenesis, NE development, and AMPK pathway activation.
      Emerging reports have revealed that AMPK activation is a potential mechanism for
      hypoxia-induced autophagy. In line with this, we demonstrate that REST knockdown
      alone is capable of activating AMPK and autophagy activation is essential for
      hypoxia-induced NED of PCa cells. Here, making using of in vitro cell-based assay
      for NED, we reveal a new role for the transcriptional repressor REST in hypoxia
      induced NED and characterized a sequential molecular mechanism downstream of REST
      resulting in AMPK phosphorylation and autophagy activation, which may be a common
      signaling pathway leading to NED of PCa. 

PMID- 27034168
TI  - Genetic polymorphisms of immune checkpoint proteins PD-1 and TIM-3 are associated
      with survival of patients with hepatitis B virus-related hepatocellular
      carcinoma.
AB  - Programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin
      domain containing molecule 3 (TIM-3) are involved in hepatitis B virus (HBV)
      infection and hepatocellular carcinoma (HCC). This study examined the
      associations of PD1 and TIM3 polymorphisms with the overall survival (OS) of a
      prospective cohort of 258 HBV-related HCC patients. Results showed that PD1 +8669
      G allele-containing genotypes or TIM3 -1516 genotype GG were significantly
      associated with longer OS (P < 0.001 and P = 0.001, respectively). In
      multivariate analysis, PD1 +8669 G allele-containing genotypes and TIM3 -1516
      genotype GG were independently associated with longer OS (hazard ratio (HR),
      1.835; 95% confidence interval (CI), 1.342-2.509; P < 0.001 and HR, 2.070; 95%CI,
      1.428-3.002; P < 0.001, respectively). PD1 +8669 G allele-containing genotypes
      were significantly associated with longer OS in patients receiving surgical
      (resection or radiofrequency) treatment, transcatheter arterial chemoembolization
      (TACE) or supportive and symptomatic treatment. TIM3 -1516 genotype GG was
      significantly associated with longer OS in TACE patients. In multivariate
      analysis, PD1 +8669 G allele-containing genotypes were independently associated
      with longer OS in each treatment population. TIM3 -1516 genotype GG was
      independently associated with longer OS in patients receiving surgical treatment
      or TACE. These findings suggest that PD1 +8669 A/G and TIM3 -1516 G/T
      polymorphisms may affect the prognosis of HBV-related HCC and may be new
      predictors of prognosis for HCC patients. 

PMID- 27034169
TI  - The GSK3beta inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell
      lines by decreasing SMADs expression level.
AB  - The Yes-associated protein, YAP, is a transcriptional co-activator, mediating the
      Epithelial to Mesenchymal Transition program in pancreatic ductal adenocarcinoma
      (PDAC). With the aim to identify compounds that can specifically modulate YAP
      functionality in PDAC cell lines, we performed a small scale, drug-based
      screening experiment using YAP cell localization as the read-out. We identified
      erlotinib as an inducer of YAP cytoplasmic localization, an inhibitor of the TEA
      luciferase reporter system and the expression of the bona fide YAP target gene,
      Connective Tissue Growth Factor CTGF. On the other hand, BIS I, an inhibitor of
      PKCdelta and GSK3beta, caused YAP accumulation into the nucleus. Activation of
      beta-catenin reporter and interfering experiments show that inhibition of the
      PKCdelta/GSK3beta pathway triggers YAP nuclear accumulation inducing YAP/TEAD
      transcriptional response. Inhibition of GSK3beta by BIS I reduced the expression
      levels of SMADs protein and reduced YAP contribution to EMT. Notably, BIS I
      reduced proliferation, migration and clonogenicity of PDAC cells in vitro,
      phenocopying YAP genetic down-regulation. As shown by chromatin
      immunoprecipitation experiments and YAP over-expressing rescue experiments, BIS I
      reverted YAP-dependent EMT program by modulating the expression of the YAP target
      genes E-cadherin, vimentin, CTGF and of the newly identified target, CD133. In
      conclusion, we identified two different molecules, erlotinib and BIS I,
      modulating YAP functionality although via different mechanisms of action, with
      the second one specifically inhibiting the YAP-dependent EMT program in PDAC cell
      lines. 

PMID- 27034170
TI  - Establishment of prostate cancer spheres from a prostate cancer cell line after
      phenethyl isothiocyanate treatment and discovery of androgen-dependent reversible
      differentiation between sphere and neuroendocrine cells.
AB  - Prostate cancer can transform from androgen-responsive to an androgen-independent
      phenotype. The mechanism responsible for the transformation remains unclear. We
      studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC),
      on the androgen-responsive LNCaP cells. After treatment with PEITC, floating
      spheres were formed with characteristics of prostate cancer stem cells (PCSC).
      These spheres were capable of self-renewal in media with and without androgen.
      They have been maintained in both types of media as long term cultures. Upon
      androgen deprivation, the adherent spheres differentiated to neuroendocrine cells
      (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC
      reverse differentiated to spheres when androgen was replenished. The sphere cells
      expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1
      down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated
      alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas
      reversible androgenomic alterations govern the shuttling between sphere PCSC and
      progeny NEC. Our findings identify unrecognized properties of prostate cancer
      sphere cells with multi-potential plasticity. This system will facilitate
      development of novel therapeutic agents and allow further exploration into
      epigenomics and androgenomics governing the transformation to hormone refractory
      prostate cancer. 

PMID- 27034171
TI  - Rheb may complex with RASSF1A to coordinate Hippo and TOR signaling.
AB  - The TOR pathway is a vital component of cellular homeostasis that controls the
      synthesis of proteins, nucleic acids and lipids. Its core is the TOR kinase.
      Activation of the TOR pathway suppresses autophagy, which plays a vital but
      complex role in tumorigenesis. The TOR pathway is regulated by activation of the
      Ras-related protein Rheb, which can bind mTOR. The Hippo pathway is a major
      growth control module that regulates cell growth, differentiation and apoptosis.
      Its core consists of an MST/LATS kinase cascade that can be activated by the
      RASSF1A tumor suppressor. The TOR and Hippo pathways may be coordinately
      regulated to promote cellular homeostasis. However, the links between the
      pathways remain only partially understood. We now demonstrate that in addition to
      mTOR regulation, Rheb also impacts the Hippo pathway by forming a complex with
      RASSF1A. Using stable clones of two human lung tumor cell lines (NCI-H1792 and
      NCI-H1299) with shRNA-mediated silencing or ectopic overexpression of RASSF1A, we
      show that activated Rheb stimulates the Hippo pathway, but is suppressed in its
      ability to stimulate the TOR pathway. Moreover, by selectively labeling
      autophagic vacuoles we show that RASSF1A inhibits the ability of Rheb to suppress
      autophagy and enhance cell growth. Thus, we identify a new connection that
      impacts coordination of Hippo and TOR signaling. As RASSF1A expression is
      frequently lost in human tumors, the RASSF1A status of a tumor may impact not
      just its Hippo pathway status, but also its TOR pathway status. 

PMID- 27034174
TI  - Association between sleep condition and arterial stiffness in Chinese adult with
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver (NAFLD) usually has worse cardiovascular risk factors.
      Given the potential association between deterioration of sleep and arterial
      stiffness, we aim to investigate the association between deterioration of sleep
      and arterial stiffness in a middle-aged Chinese population with NAFLD. In this
      cross-sectional study, 15,372 Chinese aged 40-60 years who participated in
      periodic health checkups in central south China, were included. Self-reported
      sleep duration and sleep quality, anthropometric, biochemical, and liver
      ultrasound scan were analyzed and brachial-ankle pulse wave velocity (baPWV) was
      used as the indicator of arterial stiffness. Poor sleep quality was found to be
      associated with increased arterial stiffness, with odds ratios and 95 %
      confidence intervals (CIs) of 2.28 (95 % CI, 1.53-3.38) compared with good sleep
      quality. Using sleep duration >= 8 h as the reference, there was no significant
      association between sleep duration of <= 6 or 6-8 h and arterial stiffness after
      multivariable-adjusted. In additional analyses, further investigation of the
      association of different combinations of sleep duration and quality in relation
      to arterial stiffness indicated participants with poor sleep quality and sleep
      duration <= 6 h were more likely to have arterial stiffness than those with good
      quality sleep who sleep for >= 8 h (OR 2.59, 95 % CI 1.58-4.24). The present
      study indicates that short sleep duration, poor sleep quality in individuals with
      NAFLD correlate with increased arterial stiffness. 

PMID- 27034172
TI  - Low bone mineral density and vitamin d deficiency correlated with genetics and
      other bone markers in female Turkish immigrants in Germany.
AB  - Patients with osteoporosis have a low bone mass resulting in an increased risk
      for bone fractures, morbidity and mortality. One hundred thirty-one female pre
      menopausal participants (98 Turkish immigrants living in Germany in comparison
      with 33 age-matched healthy Germans) were recruited for this study which explored
      vitamin D deficiency and specific genetic modifications of bone metabolism. The
      subjects were investigated for their femoral and lumbar bone mineral density
      (BMD) by dual-energy X-ray absorptiometry (DEXA) of the right total femur and the
      lumbar spine. Serum levels of osteologic parameters were determined: parathormone
      (PTH), calcium (Ca), osteocalcin (OC), phosphate (P), alkaline phosphatase (AP),
      beta-crossLaps (CL), tartrate-resistant acid phosphatase isoform 5b (TRAP5b), and
      25-vitamin D3 (25-OH D3). The Bsml- and Fokl-polymorphisms of the vitamin D
      receptor (VDR) gene and the collagen type I alpha 1 (COLIA1)-gene polymorphism
      were also genotyped. An extremely high prevalence of vitamin D deficiency could
      be found in the immigrant cohort (87.8 %). Osteoporosis but not osteopenia was
      more prevalent in this group. Among immigrants with osteoporosis, TRAP5b was
      elevated in 42.9 % and beta-CL in 28.6 %. Only the Fokl FF-genotype of the VDR
      polymorphism was significantly more prevalent among the Turkish women, Ff
      genotyped immigrants showed significantly decreased BMD. A significant
      correlation between the COLIA1-gene polymorphism and BMD could not be identified
      in the two groups. Vitamin D deficiency and osteoporosis appear to be dominant
      and unrecognized problem among female Turkish immigrants in Germany. Therefore,
      in this population, osteologic parameters and BMD should be routinely analyzed
      and deficiencies be treated immediately.

PMID- 27034175
TI  - Stereotactic Radiosurgery: Treatment of Brain Metastasis Without Interruption of
      Systemic Therapy.
AB  - PURPOSE: To evaluate the prevalence, outcomes, and toxicities of concurrent
      delivery of systemic therapy with stereotactic radiosurgery (SRS) for treatment
      of brain metastases. METHODS AND MATERIALS: We conducted a retrospective review
      of 193 patients treated at our institution with SRS without prior whole-brain
      radiation therapy (WBRT) for brain metastases between 2009 and 2014. Outcome
      metrics included administration of concurrent systemic therapy, myelosuppression,
      neurotoxicity, and survival. RESULTS: One hundred ninety-three patients with a
      median age of 61 years underwent a total of 291 SRS treatments. Thirty-seven
      percent of SRS treatments were delivered concurrently with systemic therapy, of
      which 46% were with conventional myelosuppressive chemotherapy, and 54% with
      targeted and immune therapy agents. Myelosuppression was minimal after treatment
      with both systemic therapy and SRS, with 14% grade 3-4 toxicity for lymphopenia
      and 4-9% for leukopenia, neutropenia, anemia, and thrombocytopenia. Neurotoxicity
      was also minimal after combined therapy, with no grade 4 and <5% grade 3
      toxicity, 34% dexamethasone requirement, and 4% radiation necrosis, all similar
      to treatments with SRS alone. Median overall survival was similar after SRS alone
      (14.4 months) versus SRS with systemic therapy (12.9 months). In patients with a
      new diagnosis of primary cancer with brain metastasis, early treatment with
      concurrent systemic therapy and SRS correlated with improved survival versus SRS
      alone (41.6 vs 21.5 months, P<.05). CONCLUSIONS: Systemic therapy can be safely
      given concurrently with SRS for brain metastases: our results suggest minimal
      myelosuppression and neurotoxicity. Concurrent therapy is an attractive option
      for patients who have both intracranial and extracranial metastatic disease and
      may be particularly beneficial in patients with a new diagnosis of primary cancer
      with brain metastasis.

PMID- 27034176
TI  - Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor
      Receptor-Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases.
AB  - PURPOSE: To perform a retrospective analysis of patients with epidermal growth
      factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases
      (BM) to evaluate our hypothesis that the use of upfront EGFR-tyrosine kinase
      inhibitors (TKIs), and deferral of radiation therapy (RT), would result in
      inferior intracranial progression-free survival but similar overall survival
      (OS). METHODS AND MATERIALS: Of 202 patients diagnosed with EGFR-mutant NSCLC
      between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients
      were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure
      to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic
      radiosurgery (SRS) or <6 months' follow-up. Of the remaining 50 patients, 17
      received upfront EGFR-TKI followed by SRS or WBRT, 17 WBRT then EGFR-TKI, and 16
      SRS followed by EGFR-TKI. Disease-specific-graded prognostic assessment was
      similar among all 3 groups. RESULTS: The median OS was longer in the upfront RT
      group compared with the upfront EGFR-TKI group (34.1 vs 19.4 months; P=.01). On
      subgroup analysis, the SRS group had longer OS than the upfront EGFR-TKI group
      (58.4 vs 19.4 months; P=.01), but the WBRT group did not (29.9 vs 19.4 months;
      P=.09). Intracranial progression-free survival was improved in patients receiving
      upfront RT compared with those receiving upfront EGFR-TKI (37.9 vs 10.6 months;
      P<.001). CONCLUSIONS: The present study suggests that the use of upfront EGFR
      TKI, and the deferral of SRS or WBRT, may result in inferior OS in patients with
      EGFR-mutant NSCLC who develop brain metastases. A prospective, multi
      institutional, randomized trial of upfront EGFR-TKI with RT at intracranial
      progression versus upfront RT followed by EGFR-TKI is urgently needed.

PMID- 27034177
TI  - Comparison of Mammographic Changes Across Three Different Fractionation Schedules
      for Early-Stage Breast Cancer.
AB  - PURPOSE: As the use of hypofractionated breast radiation therapy (RT) increases,
      so will the need for long-term data on post-RT mammographic changes. The purpose
      of the present study was to longitudinally compare the incidence of common
      mammographic sequelae seen after breast conserving surgery and RT in patients
      treated with accelerated partial breast irradiation (APBI), hypofractionated
      whole breast irradiation (HWBI), and conventionally fractionated whole breast
      irradiation (WBI). METHODS AND MATERIALS: Patients treated with either APBI or
      HWBI after breast conserving therapy and with >=3 mammograms of the treated
      breast were identified. They were matched 1:1 by age +/-5 years to patients
      treated with WBI. The mammograms were evaluated for common post-RT breast
      findings by a mammographer who was unaware of the treatment. The outcomes were
      analyzed using a cumulative logistic regression model; P<.05 indicated
      statistically significance. RESULTS: Of 89 patients treated with RT from 2006 to
      2011, 29 had received APBI, 30 had received HWBI, and 30 had received WBI. Their
      median age was 60 years (range 33-83). A total of 605 mammograms were evaluated,
      with a median follow-up of 48 months. The treatment technique did not affect the
      severity of architectural distortion when the groups were evaluated
      longitudinally. The likelihood of finding skin thickening decreased with
      increasing follow-up duration (odds ratio 0.6; P<.001) adjusted for fractionation
      schemes. No differences were seen with respect to changes in skin thickening,
      fluid collections, or calcifications among the treatment groups, after adjustment
      for the follow-up time. The clinical characteristics, including age, race, T
      stage, and chemotherapy use, were not linked to the likelihood of finding several
      mammographic phenomena over time. CONCLUSIONS: Although specific post-treatment
      imaging findings evolved over time, RT fractionation did not alter the relative
      incidence or severity of architectural distortion, skin thickening, fluid
      collections, or calcifications. These findings will be useful to both
      radiologists and radiation oncologists when counseling patients regarding follow
      up studies after RT.

PMID- 27034178
TI  - Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse
      Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of
      Life.
AB  - PURPOSE: To evaluate the dosimetric superiority, efficacy, toxicity, and quality
      of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients
      with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). METHODS AND
      MATERIALS: Forty-six consecutive patients with early-stage PG-DLBCL underwent
      IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as
      the non-germinal center B cell-like subtype. Dosimetric parameters of the
      planning target volume (PTV) and organs at risk were assessed. Survival rates
      were depicted with the Kaplan-Meier method and compared with the log-rank test.
      Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last
      follow-up contact. RESULTS: The median PTV mean dose was 41.6 Gy. Only 0.73% of
      the PTV received <95% of the prescribed dose, indicating excellent target
      coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively.
      The 5-year overall survival (OS), progression-free survival, and locoregional
      control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage,
      lactate dehydrogenase level, and immunophenotype were significant prognostic
      factors for OS, and only stage was a significant factor for locoregional control.
      Consolidation IMRT in patients with complete response after chemotherapy resulted
      in significantly better OS and progression-free survival than salvage IMRT in
      patients with non-complete response. Two of 8 patients who had chronic liver
      disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles
      of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late
      toxicity was observed. The long-term global and functional QOL scales were
      excellent, with negligible symptom scales. CONCLUSIONS: Intensity modulated
      radiation therapy yielded excellent target coverage and critical tissue sparing
      and achieved favorable outcomes with acceptable toxicity and good long-term QOL
      in early-stage PG-DLBCL.

PMID- 27034179
TI  - Trends in Local Therapy Utilization and Cost for Early-Stage Breast Cancer in
      Older Women: Implications for Payment and Policy Reform.
AB  - PURPOSE: Older women with early-stage disease constitute the most rapidly growing
      breast cancer demographic, yet it is not known which local therapy strategies are
      most favored by this population in the current era. Understanding utilization
      trends and cost of local therapy is important for informing the design of bundled
      payment models as payers migrate away from fee-for-service models. We therefore
      used the Surveillance, Epidemiology, and End Results Medicare database to
      determine patterns of care and costs for local therapy among older women with
      breast cancer. METHODS AND MATERIALS: Treatment strategy and covariables were
      determined in 55,327 women age >=66 with Tis-T2N0-1M0 breast cancer who underwent
      local therapy between 2000 and 2008. Trends in local therapy were characterized
      using Joinpoint. Polychotomous logistic regression determined predictors of local
      therapy. The median aggregate cost over the first 24 months after diagnosis was
      determined from Medicare claims through 2010 and reported in 2014 dollars.
      RESULTS: The median age was 75. Local therapy distribution was as follows: 27,896
      (50.3%) lumpectomy with external beam radiation, 18,356 (33.1%) mastectomy alone,
      6159 (11.1%) lumpectomy alone, 1488 (2.7%) mastectomy with reconstruction, and
      1455 (2.6%) lumpectomy with brachytherapy. Mastectomy alone declined from 39.0%
      in 2000 to 28.2% in 2008, and the use of breast conserving local therapies rose
      from 58.7% to 68.2%. Mastectomy with reconstruction was more common among the
      youngest, healthiest patients, whereas mastectomy alone was more common among
      patients living in rural low-income regions. By 2008, the costs were $36,749 for
      lumpectomy with brachytherapy, $35,030 for mastectomy with reconstruction,
      $31,388 for lumpectomy with external beam radiation, $21,993 for mastectomy
      alone, and $19,287 for lumpectomy alone. CONCLUSIONS: The use of mastectomy alone
      in older women declined in favor of breast conserving strategies between 2000 and
      2008. Using these cost estimates, price points for local therapy bundles can be
      constructed to incentivize the treatment strategies that confer the highest
      value.

PMID- 27034180
TI  - Recurrence rates and survival in a Danish cohort with renal cell carcinoma.
AB  - INTRODUCTION: Patients with localised and locally advanced renal cancer
      experience about 20% recurrence during a five-year follow-up period. The aim of
      the present study was to report recurrence rates and survival in a Danish
      population with renal cancer. METHODS: Data on patients diagnosed with renal cell
      carcinoma (RCC) at our institute from January 2005 to December 2013 were
      collected retrospectively. RESULTS: Overall, 367 patients were diagnosed with RCC
      during the period, and 78 patients (21%) presented with metastasis. The mean
      follow-up period for all patients was 41 months (standard deviation = 29, 95%
      confidence interval: 38-44). The total recurrence rates (RRs) at one, three and
      five years were 4.5%, 13.5% and 22.3%, respectively. Overall survival rates in
      the patients who underwent surgery with localised and locally advanced disease
      were 96.1%, 88.2% and 78.3% for one, three and five years, respectively. The mean
      time to first recurrence was 26.6 months. The one-year RR was 1.2%, 5.5% and
      13.8% for low, intermediate and high-risk Leibovich scores, respectively. The
      three-year RR was 8.3%, 14.1% and 29.6% for low, intermediate and high-risk
      Leibovich scores, respectively; and the five-year RR was 12.0%, 26.6% and 52.9%
      for low, intermediate and high-risk Leibovich scores, respectively. CONCLUSIONS:
      RRs after localised and locally advanced RCC was 22%. According to the risk of
      recurrence, we recommend a follow-up programme after nephrectomy with computed
      tomography every second year for low-risk patients, annually for intermediate
      risk patients and every six months for high-risk patients. FUNDING: none. TRIAL
      REGISTRATION: none.

PMID- 27034181
TI  - Preoperative blood glucose and prognosis in diabetic patients undergoing lower
      extremity amputation.
AB  - INTRODUCTION: Previous work has shown that uncontrolled diabetes mellitus is
      associated with adverse surgical outcomes. The purpose of the present study was
      to establish if a high peri-operative random blood sugar (RBS) concentration
      among patients with diabetes with non-traumatic lower-extremity amputation (LEA)
      is a decisive factor behind post-operative outcomes (re-amputation/mortality)
      within three months after the first amputation. METHODS: In this retrospective
      cohort study, the independent sample t-test, Pearson's chi-squared test and a Cox
      proportional hazards model were used. RESULTS: A total of 270 patients underwent
      non-traumatic LEA of whom 105 had diabetes, whereas 81 patients were included for
      this study. The mean age was 71 years (standard deviation: +/- 11.8). Mortality
      was 27% and 16% were re-amputated within three months after their first
      amputation.The median pre-operative RBS level was 8.6 mmol/l (range: 4.6-18.7
      mmol/l) with tertile ranges as follows: Q1 4.0-7.0 mmol/l; Q2 7.1-11.0 mmol/l; Q3
      > 11.0 mmol/l. For the Q3 tertile, the age-adjusted hazard ratio for re
      amputation was 0.77 (95% confidence interval (CI): 0.16-3.62) and for mortality
      it was 1.90 (95% CI: 0.50-7.22), with the Q1 tertile as the reference group.
      CONCLUSIONS: This study does not confirm that a high peri-operative RBS level can
      predict increased mortality or re-amputation among patients with diabetes who
      undergo non-traumatic LEA. Furthermore, based on our results, we cannot inform
      clinical decision-making about whether to delay or to avoid elective surgery in
      patients with a high RBS preoperatively. Further investigation is warranted.
      FUNDING: none. TRIAL REGISTRATION: This trial was registered with the Danish Data
      Protection Agency (record no. 01975 HVH-2012-053).

PMID- 27034182
TI  - Prefilled syringes for intravitreal injection reduce preparation time.
AB  - INTRODUCTION: The demand for intravitreal therapy has increased dramatically with
      the introduction of vascular endo-thelial growth factor inhibitors. Improved
      utilisation of existing resources is crucial to meeting the increased future
      demand. We investigated time spent preparing intravitreal injection treatment
      using either prefilled syringes or vials in routine clinical practice. METHODS:
      We video-recorded preparations of intravitreal injections (n = 172) for each
      preparation type (ranibizumab prefilled syringe (n = 56), ranibizumab vial (n =
      56) and aflibercept vial (n = 60)) in a multi-centre time and motion study. The
      preparation times for each step were extracted from videos and the three
      preparation types were compared. RESULTS: Prefilled syringes eliminated several
      steps in the preparation process. Total preparation time was 40.3-45.1 sec. using
      vials, and the use of prefilled syringes saved 25.5 sec. (95% confidence interval
      (CI): 23.3-27.6 sec., p < 0.0001). The preparation time when aflibercept vials
      were used was 3.7 sec. (95% CI: 1.45-5.96 sec., p = 0.0014) longer than when
      ranibizumab vials were used. CONCLUSIONS: Prefilled syringes for intravitreal
      injections reduce preparation time by eliminating preparation steps that both
      entail a risk of contamination and are subject to variation. The amount of time
      saved may enable increased utilisation of existing resources and outsourcing to
      non-ophthalmologists. FUNDING: This study was supported by a grant from Novartis.
      The funders had no influence on the design of the study, analysis of the data,
      preparation of the manuscript or the decision to publish. TRIAL REGISTRATION: not
      relevant.

PMID- 27034183
TI  - Cystectomy for bladder cancer in Denmark during the 2006-2013 period.
AB  - INTRODUCTION: The treatment of bladder cancer has been centralised in Denmark,
      and only five departments are licensed to perform radical cystectomy (RC). The
      purpose of this nationwide study was to evaluate perioperative mortality, length
      of post-operative hospital stay (LOS) and readmissions related to time course,
      surgical technique and number of RCs performed. METHODS: Patients were identified
      from the Danish National Hospital Register. We included all patients who had a RC
      performed because of bladder cancer in the period 2006-2013. RESULTS: A total of
      1,857 RCs were performed, 81% of which were open and 19% were robot-assisted
      operations. Median LOS ranged 8-15 days, with the minimum LOS at the end of
      period. Readmission within 30 days occurred in 35% of patients. For patients
      operated with open technique, the readmission rate was 32% versus 45% for robot
      assisted surgery. The 30-day mortality was 1.3% of which 1.5% occurred after open
      and 0.6% after robot-assisted RC. CONCLUSIONS: The study shows an increase in the
      number of RCs performed and a decrease in LOS during the study period.
      Furthermore, the study reveals a significant uptake of robot-assisted RC without
      obvious demonstrable benefits in terms of LOS and readmissions, but with a
      slightly lower mortality. Selection criteria for robot-assisted RC as well as
      data on tumour stage and preoperative co-morbidities are not available;
      therefore, interdepartmental comparison is not possible. However, these
      nationwide data suggest room for improvement through integration of the fast
      track methodology combined with optimisation of surgical technique. FUNDING:
      none. TRIAL REGISTRATION: not relevant.

PMID- 27034184
TI  - Characteristics of first-trimester screening of non-responders in a high-uptake
      population.
AB  - INTRODUCTION: Our aim was to compare demographic, social and reproductive health
      related medical factors between women who did and women who did not undergo
      combined first-trimester screening (cFTS) and to examine their reasons for
      declining a screening offer, especially whether non-participation was an informed
      choice. METHODS: This was a nationwide survey conducted in Denmark in 2014. A
      structured questionnaire with 33 questions relating to demographical data and
      medical history was mailed to 1,495 randomly selected women who gave birth in
      2012. Half of the women were selected among the population without cFTS, the
      other half from those with cFTS. A cohort of 20 women tested the questionnaire
      for consistency. The results are based on the responders (58%). RESULTS: The
      response rate was 88% among the women with cFTS and 19% among the women without.
      Not having a cFTS performed was associated with the following factors: country of
      origin other than Denmark (p < 0.01), less education (p < 0.01) and unemployment
      (p < 0.01). These women more often had a religious belief (p < 0.01), and had
      undergone fewer induced abortions (p = 0.01). They felt less informed about the
      cFTS (p < 0.01) and thought it was a more difficult decision (p < 0.01) than the
      women who had undergone cFTS. The main reason for declining cFTS was a wish to
      keep the child regardless of any cFTS results (82%). CONCLUSIONS: Women without
      cFTS differ from those who undergo cFTS. Not undergoing cFTS seemed most often to
      be the result of a conscious choice based on ethical considerations, rather than
      being the result of a lack of information. However, a low response rate decreases
      the strength of our conclusions. FUNDING: none. TRIAL REGISTRATION: not relevant.

PMID- 27034185
TI  - Endoscopic treatment of colorectal perforations--a systematic review.
AB  - INTRODUCTION: Iatrogenic colon perforation is a feared complication to
      colonoscopy. Optimal management of the complication remains controversial.
      Traditionally, patients have been referred to surgery. Now, with technological
      advances, endoscopic closure is increasingly performed as minimally invasive
      therapy. The aim of this systematic review was to assess the existing evidence in
      this field. METHODS: Literature was searched on PubMed, Embase and the Cochrane
      databases. Papers found were reported according to the PRISMA guidelines. Trials
      on animals were excluded. RESULTS: A total of 32 articles were assessed,
      including 19 case reports, one case control, three prospective studies and nine
      retrospective studies. The total number of patients who have undergone endoscopic
      closure (apart from case reports) and reported in the literature is 203 patients.
      Studies have reported a clinical success rate of 87.8% (standard deviation: +/-
      13.0%) on average and a median of 92.3% (range: 58.6-100%). The total number of
      patients needing surgery after attempted clip closure was 30 (14.7%); another
      four were found to have sealed perforations during surgery. One patient died
      after clip failure (0.5%). Articles presented a favourable, high outcome for
      endoscopic closure of iatrogenic colorectal perforations. CONCLUSION: In a highly
      selective group of patients, endoscopic closure of iatrogenic colon perforations
      is recommended if the expertise is available.

PMID- 27034186
TI  - Endocrine and metabolic characteristics in polycystic ovary syndrome.
AB  - Hirsutism affects 5-25% women, and the condition is most often caused by
      polycystic ovary syndrome (PCOS). The initial evaluation of hirsute patients
      should include a thorough medical history, clinical evaluation, and standardized
      blood samples to diagnose the 5% hirsute patients with rare endocrine disorders.
      The majority of these examinations can be performed by the patient's general
      practitioner. PCOS is a diagnosis of exclusion and is a multiorgan disease
      affecting most endocrine organs including ovaries, adrenals, pituitary, fat
      cells, and endocrine pancreas. The manifestations of PCOS are diverse, and up to
      50% patients are normal weight. In most cases, however, the severity of symptoms
      can be related to abdominal obesity. Increased inflammation in PCOS can be
      measured as decreased adiponectin levels and increased levels of adipokines,
      chemokines, and interleukins. In the present thesis the use of these inflammatory
      markers is reviewed, but more data including hard end points are needed to
      determine which of these markers that should be introduced to the daily clinic.
      Abdominal obesity and insulin resistance stimulates ovarian and adrenal androgen
      production, whereas SHBG levels are decreased. Increased testosterone levels may
      further increase abdominal obesity and inflammation, therefore describing PCOS as
      a vicious cycle. Abdominal obesity and increased activation of the inflammatory
      system is seen in both normal weight and obese PCOS patients leading to an
      increased risk of dyslipidemia, diabetes, and possibly cardiovascular disease.
      Patients diagnosed with PCOS therefore should be screened for elements in the
      metabolic syndrome including weight, waist, blood pressure, HbA1c, and lipid
      status. Our data supported that prolactin and HbA1c levels could be markers of
      cardiovascular risk and should be confirmed by prospective studies. PCOS is a
      life-long condition and treatment modalities involve lifestyle modification,
      insulin sensitizers such as metformin, or inhibition of testosterone levels with
      OCP. Treatment with pioglitazone supported that increased insulin sensitivity in
      PCOS is associated with improved inflammatory and cardiovascular risk markers.
      Our data supported that one year's metformin treatment was associated with a
      minor but significant weight loss in patients with PCOS irrespective of BMI at
      study inclusion. Treatment with OCP improved sex-hormone levels, but was
      associated with minor weight gain. Based on the study results, clinicians should
      consider the combined treatment with metformin and OCP also in normal weight
      patients with PCOS. The challenge in the future is to ensure sufficient
      evaluation and treatment of patients with hirsutism and PCOS and to determine
      which subgroups of patients should be treated by their general practitioner and
      which patients should be referred for hospital and/or gynecological evaluation
      and treatment. Furthermore more data are needed to determine the optimal follow
      up program regarding metabolic risk in different subgroups of patients with PCOS.

PMID- 27034187
TI  - Glucose-dependent insulinotropic polypeptide: effects on insulin and glucagon
      secretion in humans.
AB  - The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like
      peptide-1 (GLP-1) are secreted by enteroendocrine cells in the intestinal mucosa
      in response to nutrient ingestion. They are called incretin hormones because of
      their ability to enhance insulin secretion. However, in recent years it has
      become clear that the incretin hormones also affect glucagon secretion. While GLP
      1 decreases glucagon levels, the effect of GIP on glucagon levels has been
      unclear. The regulation of glucagon secretion is interesting, as the combination
      of inadequate insulin secretion and excessive glucagon secretion are essential
      contributors to the hyperglycaemia that characterise patients with type 2
      diabetes. Moreover, the near absence of a well-timed glucagon response
      contributes to an increased risk of hypoglycaemia in patients with type 1
      diabetes. The overall aim of this PhD thesis was to investigate how the blood
      glucose level affects the glucagon and insulin responses to GIP in healthy
      subjects (Study 1) and patients with Type 2 diabetes (Study 2), and more
      specifically to investigate the effects of GIP and GLP-1 at low blood glucose in
      patients with Type 1 diabetes without endogenous insulin secretion (Study 3). The
      investigations in the three mentioned study populations have been described in
      three original articles. The employed study designs were in randomised, placebo
      controlled, crossover set-up, in which the same research subject is subjected to
      several study days thereby acting as his own control. Interventions were
      intravenous administration of hormones GIP, GLP-1 and placebo (saline) during
      different blood glucose levels maintained (clamped) at a certain level. The end
      points were plasma concentrations of glucagon and insulin as well as the amount
      of glucose used to clamp the blood glucose levels. In Study 3, we also used
      stable glucose isotopes to estimate the endogenous glucose production and
      assessed symptoms and cognitive function during hypoglycaemia. The results from
      the three studies indicate that GIP has effects on insulin and glucagon responses
      highly dependent upon the blood glucose levels. At fasting glycaemia and lower
      levels of glycaemia, GIP acts to increase glucagon with little effect on insulin
      release. At hyperglycaemia the insulin releasing effect of GIP prevail, which
      lead to an increase in glucose disposal by approximately 75% in healthy subjects
      (Study 1) and 25% in patients with Type 2 diabetes (Study 2) relative to placebo.
      After insulin-induced hypoglycaemia in patients with type 1 diabetes (Study 3),
      GIP increase glucagon release, which probably augments endogenous glucose
      production. This was associated with a reduced need for exogenously added glucose
      to prevent hypoglycaemia. In conclusion, the studies position GIP as a
      bifunctional blood glucose stabilising hormone that glucose-dependently regulates
      insulin and glucagon responses in humans. 

PMID- 27034188
TI  - Postoperative red blood cell transfusion strategy in frail anemic elderly with
      hip fracture. A randomized controlled trial.
AB  - Hip fracture in the elderly is associated with poor recovery from physical
      disability and mortality. Perioperative blood loss is common, and anemia might be
      fatal in the frail elderly. Red blood cell transfusions might increase the risk
      of infection. In an observational study, a liberal transfusion strategy with
      hemoglobin (Hb) target of 7 mmol/l (11.3 g/dl) seemed to improve survival in
      nursing home residents with hip fracture compared to the recommended restrictive
      strategy with a Hb target of 6 mmol/l (9.7 g/dl) according to the Danish Health
      Authority. Our aim was to compare these two strategies in the frail elderly in a
      randomized controlled trial on the outcomes: recovery from physical disabilities,
      mortality, infection, infection biomarkers, and overall Quality of Life (OQoL).
      We included 284 elderly admitted to hospital for surgical hip fracture repair
      from nursing homes or sheltered housing facilities. The anemic patients were
      assigned postoperatively to the liberal or the restrictive transfusion strategy.
      Randomization divided each transfusion group into two equal blocks with regard to
      type of the residence. Hb was measured daily during the first three postoperative
      days, at least once during the following 4-6 days, then at least once a week
      during the subsequent three weeks. The transfusions were administered according
      to group assignments, but no later than 24 hours after the Hb determination, one
      unit at a time, and no more than two units per day. The intervention lasted for
      30 days after surgery. Outcome measurements were performed on days 10, 30, 90,
      and 365. Blinded assessors evaluated physical performance and OQoL. The liberal
      transfusion strategy did not improve recovery from physical disabilities,
      mortality, infection rate, or OQoL compared to the restrictive strategy. However,
      in nursing home residents, 90-day mortality rate (20%) following the liberal
      strategy was statistically significantly lower than that (36%) after the
      restrictive strategy. Per protocol, the 30-day mortality rate was statistically
      significantly lower following the liberal strategy in all patients (7% versus
      16%). No statistically significant difference was found in repeated leukocyte
      counts and C-reactive protein measurements, or in rate of all infections after
      ten days (66% versus 72%). Physical recovery from 30 days until one year after
      hip fracture surgery was improved by the liberal strategy. A liberal strategy did
      not improve 30-day OQoL. Physical performance was improved from 30 days to one
      year after fracture in patients treated according to the liberal strategy and was
      associated with better progress of OQoL in the same period. We conclude that
      according to our used Hb thresholds, the liberal Hb target of 7 mmol/l (11.3
      g/dl) improves survival in the frailest elderly (the nursing home residents)
      without impairing recovery from physical disabilities and OQoL or increasing risk
      of infections compared to the restrictive Hb target of 6 mmol/l (9.7 g/dl). The
      liberal strategy seems to improve recovery of physical performance within one
      year after hip fracture surgery which was associated with better overall QoL. 

PMID- 27034189
TI  - Low back load in airport baggage handlers.
AB  - Low back pain (LBP) constitutes a major economic problem in many countries. The
      causes of LBP are still largely unknown and several risk factors have been
      suggested including heavy lifting, which causes high compression forces of the
      tissues in the low back. Micro-fractures in the endplates of the vertebrae caused
      by compression forces have been suggested as a source of unspecific pain.
      Although airport baggage handlers exhibit a high prevalence of musculoskeletal
      complaints the amount of biomechanical research within this and similar areas is
      limited. The aims of this thesis were to perform a general description of the
      lumbar loading in baggage handlers (Paper I), to develop a generically useful
      tool to examine specific lumbar compression in a valid manner (Paper II & III),
      and to investigate the spinal loading in common work tasks for baggage handlers.
      (Paper III). We recorded electromyography during baggage handling in the baggage
      hall, by a conveyor, and inside the aircraft baggage compartment.
      Electromyography was analyzed using amplitude probability distribution functions
      (APDF) on both tasks and full day recordings and root mean square (RMS) values on
      tasks. Furthermore, we estimated L4/L5 compression and moment along with shoulder
      flexor moment with a Watbak model based on more specific subtasks. In addition,
      we built an inverse dynamics-based musculoskeletal computer model using the
      AnyBody Modeling System (AMS). Motion capture recorded the movements in 3D during
      a stooped and a kneeling lifting task simulating airport baggage handler work.
      Marker trajectories were used to drive the model. The AMS-models computed
      estimated compression forces, shear forces and the moments around the L4/L5
      joint. The compression forces were used for comparison with the vertebral
      compression tolerances reported in the literature. The RMS muscle activity was
      high in all tasks. The average peak RMS muscle activity was up to 120% EMGmax in
      the erector spinae during the baggage hall task. There were no significant
      differences between the tasks in the APDF analyses. The L4/L5 compression and
      extensor moment from Watbak were significantly higher in the baggage compartment
      task than in both the conveyor and baggage hall tasks. The stooped lifting task
      produced 5,541 N compression in the L4/L5 joint and a kneeling task produced
      4,197 N in the AMS models. These compression forces were close to the average
      compression tolerance and exceed the recommended limits for compression during
      lifting. 

PMID- 27034190
TI  - Neuromuscular exercise prior to joint arthroplasty in patients with
      osteoarthritis of the hip or knee.

PMID- 27034191
TI  - Autologous tissue transplantations for osteochondral repair.
AB  - Articular cartilage forms the articulating surface of synovial joints. Along with
      the synovial fluid it facilitates near frictionless movement in healthy joints.
      Injuries to articular cartilage in the knee are frequent and can lead to severe
      osteoarthritis, which is expected to affect 25% of the adult population by 2030.
      Hyaline cartilage does not regenerate spontaneously when injured and the current
      clinical treatment methods suffer from high cost and relatively high failure
      rates. This calls for new treatment methods to be developed. The backbone of
      developing new treatment methods for cartilage injuries is a reliable, cost
      effective, clinically relevant large animal model. Study 1 aimed at developing
      such a model. We hypothesized that in the Gottingen minipig, the repair response
      of a selection of treatment methods would be similar to what is found in a
      clinical setting, and that two defects per knee, rather than one, could be
      applied without affecting the repair outcome. We found that the outcomes of the
      applied treatments were consistent with the outcomes in clinical studies.
      Furthermore, the use of two defects per knee did not have any significant effect
      on the repair response. The Gottingen minipig model was easy to handle, cost
      effective, and provided a predictable repair response. Based on this study the
      use of two defects per knee in male Gottingen minipigs is recommended. The model
      has been implemented as the standard animal model for cartilage research at the
      Orthopedic Research Laboratory, Aarhus University Hospital. Synthetic
      osteochondral scaffolds represent an off-the-shelf, one-step treatment method,
      and preliminary clinical results have been promising. However, MRI investigations
      have shown issues related to subchondral healing. In study 2 we aimed at
      evaluating the osteochondral repair in 10 patients treated with the MaioRegen
      synthetic scaffold. Of the ten patients, two patients were re-operated due to
      treatment failure. CT imaging revealed that none of the eight remaining patients
      had complete regeneration of the subchondral bone. At 2.5 years, 6/8 patients had
      no or very limited (< 10%) bone formation in the defects and 2/8 had 50-75% bone
      formation in the treated defect. MRI showed no improvement at either one or 2.5
      years compared with baseline. Clinical outcome scores were improved at 2.5 years.
      These results raise serious concerns about the biological repair potential of the
      MaioRegen scaffold. The use of the MaioRegen scaffold has been discontinued in
      Denmark as a result of this study. An alternative treatment approach for
      osteochondral lesions is combined transplantation of autologous bone graft and
      cartilage fragments, embedded in fibrin glue. In study 3 we investigated the
      early biological and clinical outcome of autologous dual-tissue transplantation
      (ADTT). ADTT is a combined autologous bone and cartilage chips transplantation
      for treatment of osteochondral injuries. It is easily applicable and bypasses the
      need for costly cell culturing or synthetic materials. After one year, all eight
      patients had significant improvements on MRI, CT and all clinical outcome scores.
      This study establishes ADTT as a promising, low-cost, treatment option for
      osteochondral injuries in the knee. To investigate the role of the implanted
      cartilage chips, we tested the isolated effect of the chips in the newly
      developed Gottingen minipig model. In study 4 we compared ADTT with autologous
      bone graft alone. The hypothesis was that the presence of cartilage chips would
      improve the quality of the repair tissue. Twelve Gottingen minipigs were
      included, and follow-up time was six and 12 months. Follow-up consisted of
      histomorphometry, immunohistochemistry, semi-quantitative scoring and CT. There
      was significantly more hyaline cartilage in the ADTT group compared with the
      autologous bone graft group at both six and 12 months. At both six and 12 months
      there were significantly more fibrocartilage in the ADTT group compared with the
      ABG group. The presence of cartilage chips in an osteochondral defect facilitated
      the formation of fibrocartilage as opposed to fibrous tissue at both six and 12
      months. This study substantiates the chondrogenic role of cartilage chips in
      osteochondral defects, but questions the widely accepted repair mechanism
      involved in cartilage chip treatment methods. Further studies on the repair
      mechanism(s) involved are needed to improve the clinical application of
      autologous cartilage chips. 

PMID- 27034192
TI  - Rickettsia massiliae infection and SENLAT syndrome in Romania.
AB  - The purpose of this prospective study is to describe the clinical and
      epidemiological characteristics of rickettsioses in Romania, where only
      Rickettsia conorii is known by clinicians but new Rickettsia species have been
      identified recently in ticks. A total of eight patients, including a nine-year
      old child, were included between June 2011 and June 2012, in the Hospital for
      Infectious and Tropical Diseases, Bucharest, Romania. Seven cases presented
      during summer months and one in spring. Six patients presented a generalized rash
      with fever, myalgia and skin eschar. The last two patients presented a typical
      SENLAT syndrome, characterized by scalp eschar and neck lymphadenopathy. Using
      serological tools, we confirmed for the first time two cases of Rickettsia
      massiliae, the agent of spotted fever disease, and one case of Rickettsia
      slovaca, and one case of R. slovacaRickettsia raoultii the agents of SENLAT
      syndrome.

PMID- 27034193
TI  - Molecular characterization of Theileria orientalis from cattle in Ethiopia.
AB  - This study reports the first molecular characterization of Theileria orientalis
      in local breeds of cattle in Ethiopia. A conventional PCR utilizing major
      piroplasm surface protein (MPSP) gene and an established multiplexed tandem PCR
      (MT-PCR) were used to characterize T. orientalis and to assess the infection
      intensity, respectively. Of 232 blood samples tested, T. orientalis DNA was
      detected in only 2.2% of samples using conventional PCR; two genotypes buffeli
      (1.3%; 3/232) and type 5 (0.9%; 2/232) of T. orientalis were detected.
      Phylogenetic analysis revealed that the buffeli MPSP sequences from Ethiopia were
      closely related to those reported from Kenya, Sri Lanka and Myanmar, and type 5
      sequences from Ethiopia grouped with those from Korea, Japan, Vietnam and
      Thailand. A higher number of samples (3.9%; 9/232) were test-positive by MT-PCR
      and four genotypes (buffeli, chitose, ikeda and type 5) of T. orientalis were
      detected. The average intensity of infections with genotypes buffeli (DNA copy
      numbers 11,056) and type 5 (7508) were significantly higher (P<0.0001) than the
      pathogenic genotype ikeda (61 DNA copies). This first insight into T. orientalis
      from cattle in Ethiopia using MPSP gene provides a basis for future studies of T.
      orientalis in various agroclimatic zones and of the impact of oriental
      theilerosis on cattle in this and other countries of Africa.

PMID- 27034195
TI  - [Silodosin in medical expulsive therapy for distal ureteral calculi].

PMID- 27034194
TI  - DAFODIL: A novel liposome-encapsulated synergistic combination of doxorubicin and
      5FU for low dose chemotherapy.
AB  - PEGylated liposomes have transformed chemotherapeutic use of doxorubicin by
      reducing its cardiotoxicity; however, it remains unclear whether liposomal
      doxorubicin is therapeutically superior to free doxorubicin. Here, we demonstrate
      a novel PEGylated liposome system, named DAFODIL (Doxorubicin And 5-Flurouracil
      Optimally Delivered In a Liposome) that inarguably offers superior therapeutic
      efficacies compared to free drug administrations. Delivery of synergistic ratios
      of this drug pair led to greater than 90% reduction in tumor growth of murine 4T1
      mammary carcinoma in vivo. By exploiting synergistic ratios, the effect was
      achieved at remarkably low doses, far below the maximum tolerable drug doses. Our
      approach re-invents the use of liposomes for multi-drug delivery by providing a
      chemotherapy vehicle which can both reduce toxicity and improve therapeutic
      efficacy. This methodology is made feasible by the extension of the ammonium
      sulfate gradient encapsulation method to nucleobase analogues, a liposomal
      entrapment method once conceived useful only for anthracyclines. Therefore, our
      strategy can be utilized to efficiently evaluate various chemotherapy
      combinations in an effort to translate more effective combinations into the
      clinic.

PMID- 27034196
TI  - Playing the policy game: a review of the barriers to and enablers of nutrition
      policy change.
AB  - OBJECTIVE: To progress nutrition policy change and develop more effective
      advocates, it is useful to consider real-world factors and practical experiences
      of past advocacy efforts to determine the key barriers to and enablers of
      nutrition policy change. The present review aimed to identify and synthesize the
      enablers of and barriers to public policy change within the field of nutrition.
      DESIGN: Electronic databases were searched systematically for studies examining
      policy making in public health nutrition. An interpretive synthesis was
      undertaken. SETTING: International, national, state and local government
      jurisdictions within high-income, democratic countries. RESULTS: Sixty-three
      studies were selected for inclusion. Numerous themes were identified explaining
      the barriers to and enablers of policy change, all of which fell under the
      overarching category of 'political will', underpinned by a second major category,
      'public will'. Sub-themes, including pressure from industry, neoliberal ideology,
      use of emotions and values, and being visible, were prevalent in describing links
      between public will, political will and policy change. CONCLUSIONS: The
      frustration around lack of public policy change in nutrition frequently stems
      from a belief that policy making is a rational process in which evidence is used
      to assess the relative costs and benefits of options. The findings from the
      present review confirm that evidence is only one component of influencing policy
      change. For policy change to occur there needs to be the political will, and
      often the public will, for the proposed policy problem and solution. The review
      presents a suite of enablers which can assist health professionals to influence
      political and public will in future advocacy efforts.

PMID- 27034197
TI  - Global priorities for national carnivore conservation under land use change.
AB  - Mammalian carnivores have suffered the biggest range contraction among all
      biodiversity and are particularly vulnerable to habitat loss and fragmentation.
      Therefore, we identified priority areas for the conservation of mammalian
      carnivores, while accounting for species-specific requirements for connectivity
      and expected agricultural and urban expansion. While prioritizing for carnivores
      only, we were also able to test their effectiveness as surrogates for 23,110
      species of amphibians, birds, mammals and reptiles and 867 terrestrial
      ecoregions. We then assessed the risks to carnivore conservation within each
      country that makes a contribution to global carnivore conservation. We found that
      land use change will potentially lead to important range losses, particularly
      amongst already threatened carnivore species. In addition, the 17% of land
      targeted for protection under the Aichi Target 11 was found to be inadequate to
      conserve carnivores under expected land use change. Our results also highlight
      that land use change will decrease the effectiveness of carnivores to protect
      other threatened species, especially threatened amphibians. In addition, the risk
      of human-carnivore conflict is potentially high in countries where we identified
      spatial priorities for their conservation. As meeting the global biodiversity
      target will be inadequate for carnivore protection, innovative interventions are
      needed to conserve carnivores outside protected areas to compliment any proposed
      expansion of the protected area network. 

PMID- 27034198
TI  - Combination of peripheral laser photocoagulation with intravitreal bevacizumab in
      naive eyes with macular edema secondary to CRVO: prospective randomized study.

PMID- 27034199
TI  - Optical coherence tomography angiography in paracentral acute middle maculopathy
      secondary to central retinal vein occlusion.
AB  - PurposeTo report the clinical course and the optical coherence tomography
      angiography (OCTA) findings of patients presenting with paracentral acute middle
      maculopathy (PAMM) and central retinal vein occlusion (CRVO).MethodsRetrospective
      case series. Clincal records and multimodal imaging findings of patients
      presenting with PAMM and CRVO were reviewed.ResultsThree eyes of three patients
      (2 males; mean age: 66 years) were included in the study. Mean follow-up was 9
      months and images using OCTA (AngioVue OCT angiography system, Optovue, Inc.,
      Fremont, CA, USA) were available at the last follow-up visit. During follow-up,
      best corrected visual acuity (BCVA) of case 1 was unchanged at 85 ETDRS letters
      and OCTA revealed a mild attenuation of the perifoveal deep capillary plexus
      (DCP); in case 2, BCVA changed from 83 to 77 ETDRS letters and OCTA revealed
      patchy areas of attenuation and pruning of the DCP; in case 3, BCVA decreased
      from 26 to 8 ETDRS letters and OCTA revealed extensive areas of DCP
      dropout.ConclusionThe natural course of visual acuity in patients with PAMM
      secondary to CRVO may vary. In these patients, the extent of DCP dropout on OCTA
      may reflect the extent of visual acuity impairment. 

PMID- 27034200
TI  - Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular
      vitelliform dystrophy.
AB  - PurposeTo report the association and prevalence of reticular pseudodrusen (RPD)
      in eyes with newly presenting adult onset foveomacular vitelliform dystrophy
      (AFVD). To compare the strength of association with other pathologies resulting
      from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE)
      complex, including eyes with geographic atrophy (GA) and angioid
      streaks.MethodsRetrospective single-centre review of all consecutive newly
      presenting AFVD. Multimodal imaging with spectral domain optical coherence
      tomography, fundus photographs, red-free/blue light images, and fundus
      fluorescein angiograms were graded for the presence of RPD. For comparison, all
      consecutive newly presenting cases of GA and eyes with angioid streaks were
      studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3
      years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD
      3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0).
      This age difference did not reach statistical significance, P=0.1. Six (40%) had
      identifiable RPD; being a bilateral finding in 100% of patients. No males with
      AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three
      (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable
      angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding
      in eyes with newly presenting AFVD; not being restricted to AMD, but a finding
      common among diseases where pathophysiological mechanisms involve damage to
      Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports
      the concept that they occur with high but variable frequencies in eyes with
      various pathologies. 

PMID- 27034201
TI  - Glucose variability and inner retinal sensory neuropathy in persons with type 1
      diabetes mellitus.
AB  - PurposeTo quantify early neuroretinal alterations in patients with type 1
      diabetes mellitus (T1DM) and to assess whether glycemic variability contributes
      to alterations in neuroretinal structure or function.MethodsThirty patients with
      T1DM and 51 controls underwent comprehensive ophthalmic examination and
      assessment of retinal function or structure with frequency doubling perimetry
      (FDP), contrast sensitivity, dark adaptation, fundus photography, and optical
      coherence tomography (OCT). Diabetic participants wore a subcutaneous continuous
      glucose monitor for 5 days, from which makers of glycemic variability including
      the low blood glucose index (LGBI) and area under the curve (AUC) for
      hypoglycemia were derived.ResultsSixteen patients had no diabetic retinopathy
      (DR), and 14 had mild or moderate DR. Log contrast sensitivity for the DM group
      was significantly reduced (mean+/-SD=1.63+/-0.06) compared with controls (1.77+/
      0.13, P<0.001). OCT analysis revealed that the inner temporal inner nuclear layer
      (INL) was thinner in patients with T1DM (34.9+/-2.8 MUm) compared with controls
      (36.5+/-2.9 MUm) (P=0.023), although this effect lost statistical significance
      after application of the Bonferroni correction for multiple comparisons. Both
      markers of glycemic variability, the AUC for hypoglycemia (R=-0.458, P=0.006) and
      LGBI (R=-0.473, P=0.004), were negatively correlated with inner temporal INL
      thickness.ConclusionsPatients with T1DM and no to moderate DR exhibit alterations
      in inner retinal structure and function. Increased glycemic variability
      correlates with retinal thinning on OCT imaging, suggesting that fluctuations in
      blood glucose may contribute to neurodegeneration. 

PMID- 27034202
TI  - Transscleral resection without hypotensive anaesthesia vs iodine-125 plaque
      brachytherapy in the treatment of choroidal melanoma.
AB  - AimsThe aim of this study was to compare transscleral resection technique
      performed without hypotensive anaesthesia (TSRWH) with iodine-125 brachytherapy
      (IBT) in the treatment of choroidal melanoma.Patients and methodsThis was a
      retrospective surgical cohort study. Nineteen eyes treated with TSRWH were
      matched with 53 eyes treated with IBT according to: tumour size, distance to
      fovea, distance to optic nerve, and follow-up time. Best-corrected visual acuity
      (BCVA), local recurrence, secondary enucleation, metastasis, overall and specific
      survival, and complications were evaluated.ResultsPatients treated with TSRWH had
      significantly better BCVA than those treated with IBT. The local recurrence risk
      was significantly higher when ciliary body was involved (HR=11.4, 95% CI 2.24
      49.7, P=0.04). Metastatic disease was observed in 14 of 53 patients (26.4%) in
      the IBT group vs 3 patients (15.8%) in the TSRWH group (P=0.531). Multivariate
      analysis showed that iris involvement (HR=16.0, 95% CI 4.2-170.2, P=0.033) and
      large tumour (HR=2.3, 95% CI 1.2-4.8, P=0.04) increased the probability of
      metastasis. During follow-up, six patients (11.3%) in IBT group died vs two
      (10.5%) in the TSRWH group (P>=0.999). Nine patients required secondary
      enucleation: 5 (9.4%) in the IBT group vs 4 (21.1%) in the TSRWH group (P=0.231).
      The most common complications in IBT group were radiation-induced retinopathy
      (45.3%), neovascular glaucoma (28.3%), and macular oedema (24.5%), whereas
      rhegmatogenous retinal detachment (21.1%), ocular hypertension (21.1%), and
      submacular haemorrhage (15.8%) were the most frequent complications after
      TSRWH.ConclusionTSRWH is a technically challenging procedure. However, when
      performed successfully, this technique achieves better preservation of visual
      acuity than IBT and without the limitations inherent in hypotensive anaesthesia. 

PMID- 27034203
TI  - Intravitreal bevacizumab monotherapy for choroidal neovascularisation secondary
      to choroidal osteoma.
AB  - PurposeThe purpose of this study is to present the outcomes of a series of
      patients with choroidal neovascular membrane (choroidal neovascularisation (CNV))
      secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and
      methodsRetrospective series of patients with choroidal neovascularization
      secondary to choroidal osteoma. All patients underwent clinical and imaging
      assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and
      optical coherence tomography-where available), and were managed with intravitreal
      anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness
      were recorded pre treatment and at the end of the follow-up period.ResultsEight
      patients were included in this study. Of this, 6/8 had predominantly classic or
      classic and 2/8 patients had minimally classic or occult CNV. Each patient
      received 3-10 injections of bevacizumab. Median follow-up was 9 months (3-15
      months). Visual acuity improved in 5 patients, by 2-6 Snellen lines. CNV
      completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT
      reduction was 122 MUm (6 to -230 MUm).ConclusionIntravitreal bevacizumab can be
      an effective treatment modality in the management of vision threatening CNV
      secondary to choroidal osteoma. 

PMID- 27034204
TI  - Association of ZNF644, GRM6, and CTNND2 genes with high myopia in the Han Chinese
      population: Jiangsu Eye Study.
AB  - AimsHigh myopia is a common visual disorder in the world. The ZNF644, GRM6, and
      CTNND2 genes are expressed in the retina. This study aims to investigate the
      associations of these genes with high myopia in Han Chinese population.MethodsThe
      case-control association included high myopia cases (n=430) and controls (n=430)
      recruited from a population-based study, 'Jiangsu Eye Study'. Fourteen single
      nucleotide polymorphisms (SNPs) in three genes were genotyped by the TaqMan
      method using the real-time PCR system.ResultsThree SNPs GRM6-rs11746675, GRM6
      rs2067011, and GRM6-rs2645339 were associated with high myopia (odds ratio
      (OR)=0.74, P=0.003; OR=0.78, P=0.018; and OR=0.78, P=0.023; respectively). The
      significances of rs2067011 and rs2645339 disappeared after multiple testing
      corrections. Rs11746675 remained significant after correction for multiple
      testing. The genetic model analysis found that GRM6-rs11746675 and GRM6-rs2067011
      were suggestively associated with high myopia in the recessive model (OR=0.54,
      P=0.004; OR=0.52, P=0.003; respectively). Haplotype GAT for GRM6 markers
      rs2067011-rs2645339-rs762724 showed significance (P=0.0239), but such association
      did not remain significant after multiple testing corrections.ConclusionsOur data
      suggested that genetic variants in GRM6 are associated with high myopia. The
      mechanism of GRM6 in the development of high myopia need to be further
      investigated. 

PMID- 27034205
TI  - Relationships between plasma leptin levels, leptin G2548A, leptin receptor
      Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population.
AB  - The purposes of this study were to examine concentrations of leptin and
      biochemical parameters in gestational diabetes mellitus (GDM) patients and normal
      glucose tolerance (NGT) individuals, and also to explore the links of leptin
      (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin
      levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT
      individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels
      were analyzed by ELISA. Gene polymorphisms were genotyped using TaqMan real-time
      polymerase chain reaction assay. The results showed that plasma leptin levels
      were significantly higher in the impaired fasting glucose (IFG) group than NGT
      group (34.35 (26.54, 56.48) ng/mL vs 26.31 (17.99, 37.87) ng/mL, P < 0.05).
      Plasma leptin levels correlated with plasma fasting insulin levels, pre-pregnant
      body mass index, homeostasis model assessment-insulin resistance and quantitative
      insulin sensitivity check index both in GDM and NGT group (P < 0.05). However,
      neither LEP G2548A nor LEPR Gln223Arg polymorphisms were significantly associated
      with GDM risk and plasma leptin levels (P > 0.05). Our findings showed that high
      leptin level was associated with GDM. And larger and more rigorous researches
      were needed to further explore the association of LEP and LEPR gene polymorphisms
      and GDM among Chinese population. 

PMID- 27034207
TI  - ULTRASTRUCTURAL CHARACTERIZATION OF THE LYTIC CYCLE OF AN INTRANUCLEAR VIRUS
      INFECTING THE DIATOM CHAETOCEROS CF. WIGHAMII(BACILLARIOPHYCEAE) FROM CHESAPEAKE
      BAY, USA(1).
AB  - Numerous microalgal species are infected by viruses that have the potential to
      control phytoplankton dynamics by reducing host populations, preventing bloom
      formation, or causing the collapse of blooms. Here we describe a virus infecting
      the diatom Chaetoceros cf. wighamii Brightw. from the Chesapeake Bay. To
      characterize the morphology and lytic cycle of this virus, we conducted a time
      course experiment, sampling every 4 h over 72 h following viral inoculation. In
      vivo fluorescence began to decline 16 h after inoculation and was reduced to <19%
      of control cultures by the end of experiment. TEM confirmed infection within the
      first 8 h of inoculation, as indicated by the presence of virus-like particles
      (VLP) in the nuclei. VLP were present in two different arrangements: rod-like
      structures that appeared in cross-section as paracrystalline arrays of hexagonal
      shaped profiles measuring 12 +/- 2 nm in diameter and uniformly electron-dense
      hexagonal-shaped particles measuring ~ 22-28 nm in diameter. Nuclei containing
      paracrystalline arrays were most prevalent early in the infection cycle, while
      cells containing VLP increased and then declined toward the end of the cycle. The
      proportion of nuclei containing both paracrystalline arrays and VLP remained
      relatively constant. This pattern suggests that rod-like paracrystalline arrays
      fragmented to produce icosahedral VLP. C. cf. wighamii nuclear inclusion virus
      (CwNIV) is characterized by a high burst size (averaged 26,400 viruses per
      infected cell) and fast generation time that could have ecological implications
      on C. cf. wighamii population control. 

PMID- 27034206
TI  - Mitochondrial E3 ubiquitin ligase 1: A key enzyme in regulation of mitochondrial
      dynamics and functions.
AB  - Mitochondrial E3 ubiquitin ligase 1 (Mul1) is a multifunctional mitochondrial
      membrane protein with its RING domain exposed to the cytoplasm. On the one hand,
      Mul1 functions as a ubiquitin-ligase to ubiquitinate a bunch of signal molecules,
      such as mitofusin2 (Mfn2), Akt, p53 and ULK1, through its RING finger domain,
      leading to proteins degradation. On the other hand, Mul1 acts as a small
      ubiquitin-like modifiers (SUMO) E3 ligase to sumoylate certain proteins, such as
      dynamin-related protein 1 (Drp1), enhancing protein stabilization. Through the
      dual functions of ubiquitination and SUMOylation, Mul1 involves in regulation of
      many physiological and pathological processes, such as mitochondrial dynamics,
      cell growth, apoptosis and mitophagy. In addition, Mul1 can also directly
      activate or interact with some proteins, such as NF-kappaB and JNK, to take part
      in the regulation of cellular apoptosis. This review summarizes recent progress
      in relevant studies on the physiological and pathological functions of Mul1 and
      pays special attention to its role in regulation of mitochondrial dynamics.

PMID- 27034208
TI  - META-ANALYSIS OF GRAZER CONTROL OF PERIPHYTON BIOMASS ACROSS AQUATIC
      ECOSYSTEMS(1).
AB  - Grazer control of periphyton biomass has been addressed in numerous experimental
      studies in all kinds of aquatic habitats. In this meta-analysis, the results of
      865 experiments are quantitatively synthesized in order to address the following
      questions: (i) Do lotic, lentic, and marine ecosystems differ in their degree of
      grazer control of periphyton biomass? (ii) Which environmental variables affect
      the degree of grazer control? (iii) How much does the result of these experiments
      depend on facets of experimental design? Across all ecosystems, the grazers
      removed on average 59% of the periphyton biomass, with grazing being
      significantly stronger for laboratory (65%) than for field (56%) experiments.
      Neither field nor lab experiments showed a significant difference among lotic,
      lentic, and coastal habitats. Among different taxonomic consumer groups,
      crustaceans (amphipods and isopods) and trichopteran larvae removed the highest
      proportion of periphyton biomass. Grazer effects increased with increasing algal
      biomass, with decreasing resource availability and with increasing temperature,
      especially in field experiments. Grazer effects also increased with increasing
      total grazer biomass in field experiments but showed the opposite trend in lab
      experiments, indicating a tendency toward overcrowded lab experiments. Other
      aspects of experimental design, such as cage type, size, and duration of the
      study, strongly affected the outcome of the experiments, suggesting that much
      care has to be placed on the choice of experimental design. 

PMID- 27034209
TI  - MIXOTROPHIC ALGAE CONSTRAIN THE LOSS OF ORGANIC CARBON BY EXUDATION(1).
AB  - Algae of various taxonomic groups are capable of assimilating dissolved organic
      carbon (DOC) from their environments (mixotrophy). Recently, we reported that,
      with increasing biomass of mixotrophs, heterotrophic bacteria did not increase.
      We hypothesized that algal uptake of external DOC may outweigh their release of
      DOC by exudation (H1). Here, we addressed an alternative hypothesis that algae
      did not assimilate external DOC but constrained the release of DOC (H2). In
      chemostat experiments, we cultured the mixotrophic Chlamydomonas acidophila
      Negoro together with heterotrophic bacteria. As external substrates, we used
      glucose, which was potentially available for both bacteria and algae, or
      fructose, which was available only for bacteria. We increased the biomass of
      algae by the stepwise addition of phosphorus. Bacterial biomass did not increase
      in experiments using glucose or when fructose was offered, suggesting that
      mechanisms other than algal mixotrophy (H1) kept concentrations of bacteria low.
      Measured exudation rates (percent extracellular release, PER) of mixotrophic
      algae (Cd. acidophila, Chlorella protothecoides W. Kruger) were very low and
      ranged between 1.0% and 3.5% at low and moderately high phosphorus
      concentrations. In contrast, an obligately phototrophic alga (Chlamydomonas
      segnis H. Ettl) showed higher exudation rates, particularly under phosphorus
      limitation (70%). The results support H2. If mixotrophy is considered as a
      mechanism to recycle organic exudates from near the cell surface, this would
      explain why algae retained mixotrophic capabilities although they cannot compete
      with bacteria for external organic carbon. 

PMID- 27034210
TI  - EVIDENCE FOR IMPACTS OF NONINDIGENOUS MACROALGAE: A META-ANALYSIS OF EXPERIMENTAL
      FIELD STUDIES(1).
AB  - Invasions by nonindigenous macroalgal species (NIMS) potentially cause severe
      impacts on native species. We conducted a meta-analysis of 18 field-based
      manipulative experiments to quantify the direction and magnitude of impacts
      (Hedges effect size d, hereafter ES). We found significant small-to-medium
      negative effects on "macrophyte abundance" (cover, biomass of native taxa;
      EScumulative  = -0.30) and medium-to-large negative effects on "macrophyte
      assemblages" (richness, diversity, total abundance; EScumulative  = -0.70). In
      contrast, EScumulative were not significant for "macrophyte processes" (growth,
      mortality; EScumulative  = -0.39), "animal abundance" (densities; EScumulative  =
      -0.13), or "animal assemblages" (richness, diversity; EScumulative  = 0.75). The
      nonsignificant effect sizes were characterized by low sample sizes and should be
      interpreted with caution. Three study-specific effect sizes were particularly
      large (<-2.0), showing that, in specific cases, impacts can be highly negative.
      From a conservation perspective, focus could be on such worst-case scenarios.
      Still, the reported EScumulative are likely biased toward larger effects because
      only the most conspicuous NIMS have been tested and because nonsignificant
      results are less likely to be published. To better understand the impacts of
      NIMS, more manipulative experiments are needed, testing more species and under
      contrasting environmental conditions. Future studies should include procedural
      control treatments and report the abundance of the NIMS to avoid ambiguous
      interpretations. In conclusion, current experimental evidence shows that NIMS
      have, on average, small-to-large negative impacts on native plant species and
      assemblages. It is possible that these effects can result in severe consequences
      when accumulated over long time periods and large spatial scales. 

PMID- 27034211
TI  - DISTRIBUTION OF ALGAL EPIPHYTES ACROSS ENVIRONMENTAL GRADIENTS AT DIFFERENT
      SCALES: INTERTIDAL ELEVATION, HOST CANOPIES, AND HOST FRONDS(1).
AB  - Understanding epiphyte distribution in coastal communities is important because
      these organisms affect many others directly or indirectly. Yet, their
      distribution has been considerably less studied than that of their hosts and
      other primary-space holders. Identifying major sources of variation in epiphyte
      abundance is thus still a need. Environmental gradients help predict species
      distribution and are pervasive on marine shores. In this study, we test the
      notion that environmental gradients across intertidal elevation, throughout host
      canopies, and along host fronds explain a large variation in the abundance of
      sympatric epiphytes. Our model system was the assemblage of Ascophyllum nodosum
      (L.) Le Jol. and its epiphytes Vertebrata lanosa (L.) T. A. Chr. [= Polysiphonia
      lanosa (L.) Tandy], Elachista fucicola (Velley) Aresch., and Pylaiella littoralis
      (L.) Kjellm. On the coast of Nova Scotia (Canada), we found evidence of a spatial
      segregation among these species at almost all scales. While the red epiphyte V.
      lanosa was more common at high- and midintertidal elevations (peaking at
      midelevations) and on middle segments of host fronds, the brown epiphytes E.
      fucicola and P. littoralis were more common at low elevations and restricted to
      distal segments of host fronds. Canopy habitat affected abundance only for V.
      lanosa, which was more common within the host canopy than on its periphery at
      midelevations. Since the studied gradients are related to predictable changes in
      abiotic factors, the identification of likely causes behind the observed patterns
      was facilitated. Our study ends by proposing abiotic and biotic factors that
      deserve priority in the experimental testing of the forces structuring this
      assemblage. 

PMID- 27034212
TI  - RECENT VERSUS RELIC: DISCERNING THE GENETIC SIGNATURE OF FUCUS VESICULOSUS
      (HETEROKONTOPHYTA; PHAEOPHYCEAE) IN THE NORTHWESTERN ATLANTIC(1).
AB  - Fucus vesiculosus L. is one of the most widespread macrophytes in the
      northwestern Atlantic, ranging from North Carolina (USA) to Greenland (DK). We
      investigated genetic diversity, population differentiation, patterns of isolation
      by distance, and putative glacial refugial populations across seven locations
      from North Carolina (USA) to Cape Breton Island, Nova Scotia (Canada), with
      microsatellite analyses. Distinct northern versus southern (Delaware-North
      Carolina) populations were revealed by microsatellite data. Five of six
      microsatellite loci were fixed in populations in North Carolina, suggesting a
      recent founder event or a bottleneck, and the same homozygous genotype was found
      in herbarium materials collected on the North Carolina coast from more than 60
      years ago. An additional set of individuals from the northern limit in Greenland
      was included in our analysis of mitochondrial intergenic spacer (mt IGS)
      haplotypes in the northwestern Atlantic. Remarkably, 184 of 188 F. vesiculosus
      specimens from North Carolina to Greenland shared the same haplotype. Recent
      colonization of the North American shore from Europe is hypothesized based upon
      the ubiquity of this common haplotype, which was earlier reported from Europe. 

PMID- 27034213
TI  - FIRST INDUCED PLASTID GENOME MUTATIONS IN AN ALGA WITH SECONDARY PLASTIDS: psbA
      MUTATIONS IN THE DIATOM PHAEODACTYLUM TRICORNUTUM (BACILLARIOPHYCEAE) REVEAL
      CONSEQUENCES ON THE REGULATION OF PHOTOSYNTHESIS(1).
AB  - Diatoms play a crucial role in the biochemistry and ecology of most aquatic
      ecosystems, especially because of their high photosynthetic productivity. They
      often have to cope with a fluctuating light climate and a punctuated exposure to
      excess light, which can be harmful for photosynthesis. To gain insight into the
      regulation of photosynthesis in diatoms, we generated and studied mutants of the
      diatom Phaeodactylum tricornutum Bohlin carrying functionally altered versions of
      the plastidic psbA gene encoding the D1 protein of the PSII reaction center (PSII
      RC). All analyzed mutants feature an amino acid substitution in the vicinity of
      the QB -binding pocket of D1. We characterized the photosynthetic capacity of the
      mutants in comparison to wildtype cells, focusing on the way they regulate their
      photochemistry as a function of light intensity. The results show that the
      mutations resulted in constitutive changes of PSII electron transport rates. The
      extent of the impairment varies between mutants depending on the proximity of the
      mutation to the QB -binding pocket and/or to the nonheme iron within the PSII RC.
      The effects of the mutations described here for P. tricornutum are similar to
      effects in cyanobacteria and green microalgae, emphasizing the conservation of
      the D1 protein structure among photosynthetic organisms of different evolutionary
      origins. 

PMID- 27034214
TI  - PHOTOSYNTHETIC INORGANIC CARBON ACQUISITION IN AN ACID-TOLERANT, FREE-LIVING
      SPECIES OF COCCOMYXA (CHLOROPHYTA)(1).
AB  - The processes of CO2 acquisition were characterized for the acid-tolerant, free
      living chlorophyte alga, CPCC 508. rDNA data indicate an affiliation to the genus
      Coccomyxa, but distinct from other known members of the genus. The alga grows
      over a wide range of pH from 3.0 to 9.0. External carbonic anhydrase (CA) was
      detected in cells grown above pH 5, with the activity increasing marginally from
      pH 7 to 9, but most of the CA activity was internal. The capacity for HCO3 (-)
      uptake of cells treated with the CA inhibitor acetazolamide (AZA), was
      investigated by comparing the calculated rate of uncatalyzed CO2 formation with
      the rate of photosynthesis. Active bicarbonate transport occurred in cells grown
      in media above pH 7.0. Monitoring CO2 uptake and O2 evolution by membrane-inlet
      mass spectrometry demonstrated that air-grown cells reduced the CO2 concentration
      in the medium to an equilibrium concentration of 15 MUM, but AZA-treated cells
      caused a drop in extracellular CO2 concentration to a compensation concentration
      of 27 MUM at pH 8.0. CO2 -pulsing experiments with cells in the light indicated
      that the cells do not actively take up CO2 . An internal pool of unfixed
      inorganic carbon was not detected at the CO2 compensation concentration, probably
      because of the lack of active CO2 uptake, but was detectable at times before
      compensation point was reached. These results indicate that this free-living
      Coccomyxa possesses a CO2 -concentrating mechanism (CCM) due to an active
      bicarbonate-uptake system, unlike the Coccomyxa sp. occurring in symbiotic
      association with lichens. 

PMID- 27034215
TI  - LOW THERMAL LIMIT OF GROWTH RATE OF SYMBIODINIUM CALIFORNIUM (DINOPHYTA) IN
      CULTURE MAY RESTRICT THE SYMBIONT TO SOUTHERN POPULATIONS OF ITS HOST ANEMONES
      (ANTHOPLEURA SPP.; ANTHOZOA, CNIDARIA)(1).
AB  - Symbiodinium californium (#383, Banaszak et al. 1993) is one of two known
      dinoflagellate symbionts of the intertidal sea anemones Anthopleura
      elegantissima, A. xanthogrammica, and A. sola and occurs only in hosts at
      southern latitudes of the North Pacific. To investigate if temperature restricts
      the latitudinal distribution of S. californium, growth and photosynthesis at a
      range of temperatures (5 degrees C-30 degrees C) were determined for cultured
      symbionts. Mean specific growth rates were the highest between 15 degrees C and
      28 degrees C (MU 0.21-0.26 . d(-1) ) and extremely low at 5, 10, and 30 degrees C
      (0.02-0.03 . d(-1) ). Average doubling times ranged from 2.7 d (20 degrees C) to
      33 d (5, 10, and 30 degrees C). Cells cultured at 10 degrees C had the greatest
      cell volume (821 MUm(3) ) and the highest percentage of motile cells (64.5%).
      Growth and photosynthesis were uncoupled; light-saturated maximum photosynthesis
      (Pmax ) increased from 2.9 pg C . cell(-1 ) . h(-1) at 20 degrees C to 13.2 pg C
      . cell(-1 ) . h(-1) at 30 degrees C, a 4.5-fold increase. Less than 11% of daily
      photosynthetically fixed carbon was utilized for growth at 5, 10, and 30 degrees
      C, indicating the potential for high carbon translocation at these temperatures.
      Low temperature effects on growth rate, and not on photosynthesis and cell
      morphology, may restrict the distribution of S. californium to southern
      populations of its host anemones. 

PMID- 27034216
TI  - ESTABLISHMENT OF MINIMAL AND MAXIMAL TRANSCRIPT LEVELS FOR NITRATE TRANSPORTER
      GENES FOR DETECTING NITROGEN DEFICIENCY IN THE MARINE PHYTOPLANKTON ISOCHRYSIS
      GALBANA (PRYMNESIOPHYCEAE) AND THALASSIOSIRA PSEUDONANA (BACILLARIOPHYCEAE)(1).
AB  - Nitrate transporter genes (Nrt2) encode high-affinity nitrate transporters in
      marine phytoplankton, and their transcript levels are potential markers of
      nitrogen deficiency in eukaryotic phytoplankton. For the proper interpretation of
      measured Nrt2 transcript abundances, a relative expression assay was proposed and
      tested in Isochrysis galbana Parke (Prymnesiophyceae) and Thalassiosira
      pseudonana (Hust.) Hasle et Heimdal (Bacillariophyceae). The minimal transcript
      levels of Nrt2 genes were achieved by the addition of 100 MUM ammonium, which led
      to a rapid decline in Nrt2 transcripts in 10-30 min. Experiments using a
      concentration series revealed that the effective dosage of ammonium to create a
      minimal transcript level of ~1 MUmol . mol(-1) 18S rRNA was >=25 MUM in both
      species. On the other hand, the addition of l-methionine sulfoximine (MSX), an
      inhibitor of glutamine synthetase, enhanced the Nrt2 transcript level in I.
      galbana but did not affect that in T. pseudonana. Nitrogen deprivation was used
      as an alternative means to create maximal Nrt2 transcript levels. By transferring
      cells into N-free medium for 24 h, Nrt2 transcript levels increased to ~90 MUmol
      . mol(-1) 18S rRNA in I. galbana, and to ~800 MUmol . mol(-1) 18S rRNA in T.
      pseudonana. The degree of nitrogen deficiency thus can be determined by comparing
      original Nrt2 transcript levels with the minimal and maximal levels. 

PMID- 27034217
TI  - CONSTRUCTION AND CHARACTERIZATION OF A TENTATIVE AMPLIFIED FRAGMENT LENGTH
      POLYMORPHISM-SIMPLE SEQUENCE REPEAT LINKAGE MAP OF LAMINARIA (LAMINARIALES,
      PHAEOPHYTA)(1).
AB  - A tentative amplified fragment length polymorphism-simple sequence repeat (AFLP
      SSR) linkage map of Laminaria was constructed using a haploid population of 40
      gametophyte clones isolated from an individual of Dongfang No. 2, the first
      commercially cultured hybrid of a female gametophyte clone of L. japonica Aresch.
      [=Saccharina japonica (Aresch.) C. E. Lane, C. Mayes et G. W. Saunders] and a
      male one of L. longissima Miyabe [=Saccharina longissima (Miyabe) C. E. Lane, C.
      Mayes et G. W. Saunders]. To the map, 263 markers (255 AFLP, seven SSR, and the
      gametophyte sex) were assigned. The map consisted of 25 linkage groups (LGs) with
      >= four markers, five triplets, and 15 doublets, which is 1,629.0 centiMorgans
      (cM) in length, covering 66% of Laminaria genome. The maximum space between loci
      is 24.63 cM. A putative sex-determining region was identified in LG2 , which was
      characterized by a dense marker distribution around the gametophyte sex locus.
      The linkage map itself and the methodology associated with its construction will
      facilitate the genetic study and further trials of the linkage map construction
      of Laminaria. 

PMID- 27034218
TI  - CELL-WALL DEVELOPMENT AND BIPOLAR GROWTH IN THE DESMID PENIUM MARGARITACEUM
      (ZYGNEMATOPHYCEAE, STREPTOPHYTA). ASYMMETRY IN A SYMMETRIC WORLD(1).
AB  - Cell-wall (CW) development in the desmid Penium margaritaceum (Ehrenb.) Breb. was
      studied using immunofluorescence labeling of living cells with the monoclonal
      antibodies (mAbs) JIM5 and JIM7, which recognize unesterified and methyl
      esterified homogalacturonan (HG), respectively. During cell expansion, HG was
      secreted in a high-esterified form at a narrow band, called the HG secretion band
      or HGSB, at the isthmus or the polar tip of a daughter semicell. As newly
      secreted HG is displaced outward on the cell surface, deesterification and
      subsequent calcium (Ca(2+) )-complexing occurred to yield a rigid covering. HG
      secretion and CW/cell expansion were reversibly inhibited by dark, brefeldin A
      (BFA), and incubation in 0.24-0.36 M sucrose but were not altered by treatment
      with actin/microfilament drugs. The HGSB was detected near the nucleus during
      most cell-cycle events. Centrifugation displaced the nucleus away from the HGSB,
      but HG synthesis was not affected. HGSB activity was preceded by, and coordinated
      with, Calcofluor labeling, which suggests that cellulose production in CW/cell
      expansion sites was critical to expansion control. In many first-cell-division
      products, asymmetric patterning of HG was noted in the CW. These asymmetric
      patterns most likely were a result of timing mechanisms and displacement of the
      nucleus-HGSB during the cell cycle. 

PMID- 27034219
TI  - A SCAR MOLECULAR MARKER SPECIFICALLY RELATED TO THE FEMALE GAMETOPHYTES OF
      SACCHARINA (LAMINARIA) JAPONICA (PHAEOPHYTA)(1).
AB  - PCR amplification was employed to identify female or male gametophyte associated
      markers in Saccharina japonica (Aresch.) C. E. Lane, C. Mayes et G. W. Saunders
      (=Laminaria japonica Aresch.). One pair of the primers, P5, was screened from
      five pairs designed based on a specific sequence (GenBank accession no. AB069714)
      of Marchantia polymorpha Y chromosome, resulting in a differential band ~500 bp
      in size between female and male gametophytes of Rongfu strain of S. japonica.
      According to the SCAR (sequence-characterized amplified regions) strategies, one
      pair of primers, P51, was designed on the basis of the sequence of this band that
      was only present in female gametophytes. A SCAR marker, designated FRML-494 (494
      bp Female-Related Marker of S. japonica, GenBank accession no. EU931619), was
      developed successfully by PCR amplification using the designed P51 primer pair.
      The SCAR marker was verified to be present only in female gametophytes of another
      variety 901 of this kelp that was a hybrid between S. japonica as paternal and S.
      longissima (Miyabe) C. E. Lane, C. Mayes, Druehl et G. W. Saunders (=Laminaria
      longissima Miyabe) as maternal, suggesting that the FRML-494 marker was
      specifically related to female gametophytes of the genus. This marker is the
      first molecular tool reported for sex identification in kelps. This study was
      beneficial for identifying gametophyte gender during vegetative growth and for
      judging whether the monogenetic sporophytes came from exclusive male or female
      gametophytes, as well as for further research on sex determination at the
      molecular level in kelps. 

PMID- 27034220
TI  - THE RELATION BETWEEN N2 FIXATION AND H2 METABOLISM IN THE MARINE FILAMENTOUS
      NONHETEROCYSTOUS CYANOBACTERIUM LYNGBYA AESTUARII CCY 9616(1).
AB  - The marine filamentous nonheterocystous nitrogen-fixing cyanobacterium Lyngbya
      aestuarii (F. K. Mert.) Liebman ex Gomont CCY 9616 was grown under diazotrophic
      and nondiazotrophic conditions and under an alternating 16:8 light:dark (L:D)
      regime. Nitrogenase activity appeared just before the onset of the dark period,
      reaching its maximum 1-2 h in the dark, subsequently decreasing to zero at the
      beginning of the following light period. Nitrogenase activity was only detected
      at low levels of O2 (5%) and when the culture was grown in the absence of
      combined nitrogen. Quantitative reverse transcriptase-PCR (RT-PCR) analysis of
      one of the structural genes encoding nitrogenase, nifK, showed that the highest
      levels of transcription preceded the maximum activity of nitrogenase by 2-4 h.
      nifK transcription was not completely abolished during the remaining time of the
      24 h cycle. Even in the presence of nitrate, when nitrogenase activity was
      undetectable, nifK was still transcribed. The H2 -uptake activity seemed to
      follow the nitrogenase, but the transcription of hupL (gene encoding the large
      subunit of uptake hydrogenase) preceded the nifK transcription. However, H2 
      uptake and hupL transcription occurred throughout the 24 h cycle as well as under
      nondiazotrophic conditions, albeit at much lower levels. The hoxH transcript
      levels (a structural gene coding for the bidirectional hydrogenase) were similar
      under diazotrophic or nondiazotrophic conditions but slightly higher during the
      dark period. All three enzymes investigated are involved in H2 metabolism. It is
      concluded that the uptake hydrogenase is mainly responsible for H2 uptake.
      Nevertheless, uptake hydrogenase and nitrogenase do not seem to be coregulated. 

PMID- 27034221
TI  - CLASSIFICATION OF THE GENUS ISHIGE (ISHIGEALES, PHAEOPHYCEAE) IN THE NORTH
      PACIFIC OCEAN WITH RECOGNITION OF ISHIGE FOLIACEA BASED ON PLASTID rbcl AND
      MITOCHONDRIAL cox3 GENE SEQUENCES(1).
AB  - The taxonomy and biogeography of a genus with species that occur in
      geographically isolated regions is interesting. The brown algal genus Ishige
      Yendo is a good example, with species that apparently inhabit warm regions of
      both the northwestern and northeastern Pacific Ocean. We determined the sequences
      of mitochondrial cox3 and plastid rbcL genes from specimens of the genus
      collected over its distributional range. Analyses of the 86 cox3 and 97 rbcL
      sequences resulted in congruent trees in which Ishige sinicola (Setch. et N. L.
      Gardner) Chihara consisted of two distinct clades: one comprising samples from
      Korea and Japan, and the other comprising samples from the Gulf of California.
      Additional observations of the morphology and anatomy of the specimens agree with
      the molecular data. On the basis of results, we reinstated Ishige foliacea S.
      Okamura (considered a synonym of I. sinicola from the Gulf of California) for
      plants from the northwest Pacific region and designated a specimen in the Yendo
      Herbarium (SAP) as the lectotype. I. foliacea is distinguished by large (up to 20
      cm) and wide (up to 20 mm) thalli, with a cortex of 4-7 cells, and a medulla
      composed of long, tangled hyphal cells. Both cox3 and rbcL sequence data strongly
      support the sister-area relationship between the northwest Pacific region and the
      Gulf of California. A likely explanation for this pattern would be the presence
      of a species ancestral to contemporary species of Ishige in both regions during
      the paleogeological period, with descendants later isolated by distance. 

PMID- 27034222
TI  - A NEW HELICOSPHAERA-SYRACOLITHUS COMBINATION COCCOSPHERE (HAPTOPHYTA) FROM THE
      WESTERN MEDITERRANEAN SEA(1).
AB  - A new combination coccosphere of the heterococcolithophore Helicosphaera
      wallichii (Lohman 1902) Okada and McIntyre 1977 and holococcolithophore
      Syracolithus ponticuliferus (Kamptner 1941) Kleijne and Jordan 1990 is
      documented. This combination coccosphere was observed within a rich and diverse
      assemblage collected during late summer at a 20 m water depth from the NW
      Mediterranean Sea. 

PMID- 27034223
TI  - TAXONOMIC REEXAMINATION OF CHARA GLOBULARIS (CHARALES, CHAROPHYCEAE) FROM JAPAN
      BASED ON OOSPORE MORPHOLOGY AND rbcL GENE SEQUENCES, AND THE DESCRIPTION OF C.
      LEPTOSPORA SP. NOV.(1).
AB  - Chara globularis Thuillier (=f. globularis sensu R. D. Wood) is a widespread
      species of the genus and inhabits fresh- and brackish-water environments. In an
      attempt to reexamine the taxonomic status of C. globularis collected from Japan,
      we reassessed vegetative and oospore morphology of Japanese material and
      herbarium specimens originating from Europe (including the type specimen) and
      conducted molecular phylogenetic analyses based on rbcL gene sequences. Although
      the other vegetative morphologies were consistent with the description of C.
      globularis f. globularis sensu R. D. Wood, we identified two types of branchlets
      within the Japanese materials: one has elongate end segments (EL type), and the
      other has short end segments (SH type) corresponding to the type material.
      Moreover, the oospore wall of the EL type was different from that in the SH type.
      The oospores of the EL type were dark brown to reddish brown and had a spongy
      pattern with the pusticular elevations on the fossa wall, whereas the fossa wall
      of the SH type was black with a granulate to papillate or fine pusticular
      pattern. In addition, our sequence data demonstrated that these two types are
      separated phylogenetically from each other. Therefore, we describe the EL type as
      a new species, C. leptospora sp. nov. 

PMID- 27034224
TI  - HETEROGENEITY OF THE CYANOBACTERIAL GENUS SYNECHOCYSTIS AND DESCRIPTION OF A NEW
      GENUS, GEMINOCYSTIS(1).
AB  - The study and revision of the unicellular cyanobacterial genus Synechocystis was
      based on the type species S. aquatilis Sauv. and strain PCC 6803, a reference
      strain for this species. Uniformity in rRNA gene sequence, morphology, and
      ultrastructure was observed in all available Synechocystis strains, with the
      exception of the strain PCC 6308, which has been considered by some to be a model
      strain for Synechocystis. This strain differs substantially from the typical
      Synechocystis cluster according to both molecular (<90% of similarity,
      differences in 16S-23S rRNA internal transcribed spacer [ITS] secondary
      structure) and phenotypic criteria (different ultrastructure of cells). This
      strain is herein classified into the new genus Geminocystis gen. nov., as a
      sister taxon to the genus Cyanobacterium. Geminocystis differs from
      Cyanobacterium by genetic position (<94.4% of similarity) and more importantly by
      its different type of cell division. Because strain PCC 6308 was designated as a
      reference strain of the Synechocystis cluster 1 in Bergey's Manual, the members
      of this genetic cluster have to be revised and reclassified into Geminocystis
      gen. nov. Only the members of the Synechocystis cluster 2 allied with PCC 6803
      correspond both genetically and phenotypically to the type species of the genus
      Synechocystis (S. aquatilis). 

PMID- 27034225
TI  - GYMNODINIUM COROLLARIUM SP. NOV. (DINOPHYCEAE)-A NEW COLD-WATER DINOFLAGELLATE
      RESPONSIBLE FOR CYST SEDIMENTATION EVENTS IN THE BALTIC SEA(1).
AB  - A naked dinoflagellate with a unique arrangement of chloroplasts in the center of
      the cell was isolated from the northern Baltic proper during a spring
      dinoflagellate bloom (March 2005). Morphological, ultrastructural, and molecular
      analyses revealed this dinoflagellate to be undescribed and belonging to the
      genus Gymnodinium F. Stein. Gymnodinium corollarium A. M. Sundstrom, Kremp et
      Daugbjerg sp. nov. possesses features typical of Gymnodinium sensu stricto, such
      as nuclear chambers and an apical groove running in a counterclockwise direction
      around the apex. Phylogenetic analyses based on partial nuclear-encoded LSU rDNA
      sequences place the species in close proximity to G. aureolum, but significant
      genetic distance, together with distinct morphological features, such as the
      position of chloroplasts, clearly justifies separation from this species.
      Temperature and salinity experiments revealed a preference of G. corollarium for
      low salinities and temperatures, confirming it to be a cold-water species well
      adapted to the brackish water conditions in the Baltic Sea. At nitrogen-deplete
      conditions, G. corollarium cultures produced small, slightly oval cysts
      resembling a previously unidentified cyst type commonly found in sediment trap
      samples collected from the northern and central open Baltic Sea. Based on LSU
      rDNA comparison, these cysts were assigned to G. corollarium. The cysts have been
      observed in many parts of the Baltic Sea, indicating the ecologic versatility of
      the species and its importance for the Baltic ecosystem. 

PMID- 27034226
TI  - PSEUDOCODIUM MUCRONATUM, A NEW SPECIES FROM NEW CALEDONIA, AND AN ANALYSIS OF THE
      EVOLUTION OF CLIMATIC PREFERENCES IN THE GENUS (BRYOPSIDALES, CHLOROPHYTA)(1).
AB  - A new species, Pseudocodium mucronatum, is described from the Chesterfield
      platform off the west coast of New Caledonia. The species differs from its
      congeners in having mucronate utricules. A phylogenetic analysis of rbcL and tufA
      sequences showed that P. mucronatum is most closely associated with P. natalense
      De Clerck, Coppejans et Verbruggen and P. devriesii Weber Bosse, with which it
      shares compressed axes, depressed apices, and plastids in the utricles and the
      medullar siphons. We studied the evolution of climatic and ecological preferences
      in the genus using an interdisciplinary approach consisting of relaxed molecular
      clock analysis, extraction of macroecological data from satellite imagery in a
      geographic information system (GIS) framework, and ancestral character state
      estimation. It was shown that the genus originated in tropical waters during the
      Early Mesozoic. Whereas the P. floridanum-okinawense lineage remained tropical,
      the lineage including P. natalense, P. devriesii, and P. mucronatum gradually
      invaded more temperate waters during Cenozoic times. Except for P. devriesii,
      which occurs in shallow and intertidal habitats, all Pseudocodium species grow in
      deep-water habitats, and this ecological preference appears to be ancestral. 

PMID- 27034227
TI  - SEASONAL VARIABILITY OF PHYSICOCHEMICAL AND RHEOLOGICAL PROPERTIES OF ULVAN IN
      TWO ULVA SPECIES (CHLOROPHYTA) FROM THE BRITTANY COAST(1).
AB  - The seasonal variability in the extraction yield, physicochemical
      characteristics, and rheological properties of ulvan from two Ulva species
      contributing to Brittany "green tides" has been studied. These seaweeds were
      collected in the water column for Ulva armoricana Dion, de Reviers et Coat and on
      hard substrata for Ulva rotundata Bliding. The maximum ulvan extraction
      efficiency was not related to the maximum ulvan content in the seaweeds, but with
      the active growth period of the seaweeds. Ulvan chemical structure,
      macromolecular characteristics, and rheological properties were affected by both
      species and seasons. The proportion of high-molecular-weight ulvan was the major
      factor positively correlated with the gelling properties. Characteristics of
      ulvan from U. rotundata subjected to tides were more affected by seasons than
      ulvan from U. armoricana living in a more constant environment. These results
      point to several useful recommendations concerning Ulva sp. biomass collected
      with regard to ulvan characteristics and uses. 

PMID- 27034228
TI  - EVALUATION OF RECOVERABLE FUNCTIONAL LIPID COMPONENTS OF SEVERAL BROWN SEAWEEDS
      (PHAEOPHYTA) FROM JAPAN WITH SPECIAL REFERENCE TO FUCOXANTHIN AND FUCOSTEROL
      CONTENTS(1).
AB  - Fucoxanthin (Fx) and fucosterol (Fs) are characteristic lipid components of brown
      seaweeds that afford several health benefits to humans. This article describes
      the quantitative evaluation of lipids of 15 species of brown seaweeds with
      specific reference to Fx, Fs, and functional long-chain omega-6/omega-3
      polyunsaturated fatty acids (PUFAs). In addition, fatty-acid composition of
      selected species was also accomplished in the study. Major omega-3 PUFAs in the
      brown seaweeds analyzed were alpha-linolenic acid (18:3n-3), octadecatetraenoic
      acid (18:4n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3).
      Both Fx (mg . g(-1) dry weight [dwt]) and Fs (mg . g(-1) dwt) were determined to
      be relatively abundant in Sargassum horneri (Turner) C. Agardh (Fx, 3.7 +/- 1.6;
      Fs, 13.4 +/- 4.4) and Cystoseira hakodatensis (Yendo) Fensholt (Fx, 2.4 +/- 0.9;
      Fs, 8.9 +/- 2.0), as compared with other brown seaweed species. Studies related
      to seasonal variation in Fx, Fs, and total lipids of six brown algae [S. horneri,
      C. hakodatensis, Sargassum fusiforme (Harv.) Setch., Sargassum thunbergii
      (Mertens ex Roth) Kuntze, Analipus japonicus (Harv.) M. J. Wynne, and
      Melanosiphon intestinalis (D. A. Saunders) M. J. Wynne] indicated that these
      functional lipid components reached maximum during the period between January and
      March. The functional lipid components present in these seaweeds have the
      potential for application as nutraceuticals and novel functional ingredients
      after their recovery. 

PMID- 27034229
TI  - PROTOCOLS FOR THE REMOVAL OF BACTERIA FROM FRESHWATER BENTHIC DIATOM CULTURES(1).
AB  - In this study, we describe different combinations of physical separation and
      antibiotic treatment to remove associated bacteria from freshwater diatoms.
      Diatoms were purified either from natural epilithic biofilms or from unialgal
      cultures. We determined that for most strains, different purification procedures
      have to be combined individually. In a new approach, we show that for some diatom
      strains, the substitution of associated aquatic bacteria by an antibiotic
      sensitive Escherichia coli strain and subsequent treatment with antibiotics may
      be a successful strategy to obtain axenic diatom cultures. Axenic diatom cultures
      are essential to study the physiology and biochemistry of individual strains as
      well as their responses to environmental changes without interference of
      accompanying bacteria. 

PMID- 27034230
TI  - Re: CT-Based Determination of Ureteral Stone Volume: A Predictor of Spontaneous
      Passage (From: Zorba OU, Ogullar S, Yazar S, et al. J Endourol 2016;30:32-36).

PMID- 27034231
TI  - FGFR2c-mediated ERK-MAPK activity regulates coronal suture development.
AB  - Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper
      craniofacial development. A gain-of-function mutation in the 2c splice variant of
      the receptor's gene is associated with Crouzon syndrome, which is characterized
      by craniosynostosis, the premature fusion of one or more of the cranial vault
      sutures, leading to craniofacial maldevelopment. Insight into the molecular
      mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a
      critical regulator of suture patency. The aim of this study is to investigate the
      role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture
      development. Loss-of-function and gain-of-function Fgfr2c mutant mice have
      overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia.
      In vivo analysis of coronal sutures in loss-of-function and gain-of-function
      models demonstrated fundamentally different pathogenesis underlying coronal
      suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated
      enhanced osteoblastic function and maturation with concomitant increase in ERK
      MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126
      mitigated ERK protein activation levels with a concomitant reduction in alkaline
      phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as
      a key mediator of craniofacial growth and coronal suture development.
      Furthermore, our results solve the apparent paradox between loss-of-function and
      gain-of-function FGFR2c mutants with respect to coronal suture synostosis.

PMID- 27034232
TI  - 2'-5' Oligoadenylate synthetase-like 1 (OASL1) deficiency in mice promotes an
      effective anti-tumor immune response by enhancing the production of type I
      interferons.
AB  - Type I interferon (IFN-I) plays a critical role in antiviral and antitumor
      defense. In our previous studies, we showed that IFN-I-inducible 2'-5'
      oligoadenylate synthetase-like 1 (OASL1) negatively regulates IFN-I production
      upon viral infection by specifically inhibiting translation of the IFN-I
      regulating master transcription factor, interferon regulatory factor 7 (IRF7). In
      this study, we investigated whether OASL1 plays a negative role in the anti-tumor
      immune response by using OASL1-deficient (Oasl1 (-/-)) mice and transplantable
      syngeneic tumor cell models. We found that Oasl1 (-/-) mice demonstrate enhanced
      resistance to lung metastatic tumors and subcutaneously implanted tumors compared
      to wild-type (WT) mice. Additionally, we found that cytotoxic effector cells such
      as CD8(+) T cells (including tumor antigen-specific CD8(+) T cells) and NK cells
      as well as CD8alpha(+) DCs (the major antigen cross-presenting cells) were much
      more frequent (>fivefold) in the Oasl1 (-/-) mouse tumors. Furthermore, the
      cytotoxic effector cells in Oasl1 (-/-) mouse tumors seemed to be more
      functionally active. However, the proportion of immunosuppressive myeloid-derived
      suppressor cells within hematopoietic cells and of regulatory T cells within
      CD4(+) T cells in Oasl1 (-/-) mouse tumors did not differ significantly from that
      of WT mice. Tumor-challenged Oasl1 (-/-) mice expressed increased levels of IFN-I
      and IRF7 protein in the growing tumor, indicating that the enhanced antitumor
      immune response observed in Oasl1 (-/-) mice was caused by higher IFN-I
      production in Oasl1 (-/-) mice. Collectively, these results show that OASL1
      deficiency promotes the antitumor immune response, and thus, OASL1 could be a
      good therapeutic target for treating tumors.

PMID- 27034233
TI  - Endostatin inhibits the growth and migration of 4T1 mouse breast cancer cells by
      skewing macrophage polarity toward the M1 phenotype.
AB  - The phenotypic diversity of tumor-associated macrophages (TAMs) increases with
      tumor development. One of the hallmarks of malignancy is the polarization of TAMs
      from a pro-immune (M1) phenotype to an immunosuppressive (M2) phenotype. However,
      the molecular basis of this process is still unclear. Endostatin is a powerful
      inhibitor of angiogenesis capable of suppressing tumor growth and metastasis.
      Here, we demonstrate that endostatin induces RAW264.7 cell polarization toward
      the M1 phenotype in vitro. Endostatin has no effect on TAM numbers in vivo, but
      results in an increased proportion of F4/80(+)Nos2(+) cells and a decreased
      proportion of F4/80(+)CD206(+) cells. Overexpression of endostatin in RAW264.7
      cells resulted in a decrease in the phosphorylation of STAT3, an increase in
      expression of vascular endothelial growth factor A and placental growth factor,
      and an increase in the phosphorylation of STAT1, IkappaBalpha and p65 proteins
      compared with controls. These results indicate that endostatin regulates
      macrophage polarization, promoting the M1 phenotype by targeting NF-kappaB and
      STAT signaling.

PMID- 27034234
TI  - 4-1BB agonism: adding the accelerator to cancer immunotherapy.
AB  - The success of checkpoint inhibitors has validated immunomodulatory agents as a
      valuable class of anticancer therapeutics. A promising co-stimulatory immunologic
      target is 4-1BB, or CD137, a member of the tumor necrosis factor receptor
      superfamily. Ligation of 4-1BB induces an activating signal in CD8(+) T cells and
      natural killer cells, resulting in increased pro-inflammatory cytokine secretion,
      cytolytic function, and antibody-dependent cell-mediated cytotoxicity. Targeting
      4-1BB with agonistic monoclonal antibody (mAb) therapy demonstrated potent
      antitumor effects in murine tumor models. While anti-4-1BB mAbs have entered
      clinical trials, optimal efficacy of 4-1BB-targeted agents will inevitably come
      from combination therapeutic strategies. Checkpoint blockade is a compelling
      combination partner for 4-1BB agonism. This novel immunotherapeutic approach has
      the potential to active antitumor immune effectors by a complementary mechanism:
      simultaneously "removing the brakes" via blocking inhibitory signaling and
      "stepping on the accelerator" via co-stimulation. While important considerations
      should be given to 4-1BB-mediated toxicities, the current understanding of 4-1BB
      biology suggests it may play a key role in advancing the capabilities of cancer
      combination therapy.

PMID- 27034235
TI  - Differential immunomodulatory activity of tumor cell death induced by cancer
      therapeutic toll-like receptor ligands.
AB  - Synthetic toll-like receptor (TLR) ligands stimulate defined immune cell subsets
      and are currently tested as novel immunotherapeutic agents against cancer with,
      however, varying clinical efficacy. Recent data showed the expression of TLR
      receptors also on tumor cells. In this study we investigated immunological events
      associated with the induction of tumor cell death by poly(I:C) and imiquimod. A
      human head and neck squamous cell carcinoma (HNSCC) cell line was exposed to
      poly(I:C) and imiquimod, which were delivered exogenously via culture medium or
      via electroporation. Cell death and cell biological consequences thereof were
      analyzed. For in vivo analyses, a human xenograft and a syngeneic immunocompetent
      mouse model were used. Poly(I:C) induced cell death only if delivered by
      electroporation into the cytosol. Cell death induced by poly(I:C) resulted in
      cytokine release and activation of monocytes in vitro. Monocytes activated by the
      supernatant of cancer cells previously exposed to poly(I:C) recruited
      significantly more Th1 cells than monocytes exposed to control supernatants. If
      delivered exogenously, imiquimod also induced tumor cell death and some release
      of interleukin-6, but cell death was not associated with release of Th1
      cytokines, interferons, monocyte activation and Th1 recruitment. Interestingly,
      intratumoral injection of poly(I:C) triggered tumor cell death in tumor-bearing
      mice and reduced tumor growth independent of TLR signaling on host cells.
      Imiquimod did not affect tumor size. Our data suggest that common cancer
      therapeutic RNA compounds can induce functionally diverse types of cell death in
      tumor cells with implications for the use of TLR ligands in cancer immunotherapy.

PMID- 27034236
TI  - Adoptive transfer of osteoclast-expanded natural killer cells for immunotherapy
      targeting cancer stem-like cells in humanized mice.
AB  - Based on data obtained from oral, pancreatic and lung cancers, glioblastoma, and
      melanoma, we have established that natural killer (NK) cells target cancer stem
      like cells (CSCs). CSCs displaying low MHC class I, CD54, and PD-L1 are killed by
      cytotoxic NK cells and are differentiated by split anergized NK cells through
      both membrane bound and secreted forms of TNF-alpha and IFN-gamma. NK cells
      select and differentiate both healthy and transformed stem-like cells, resulting
      in target cell maturation and shaping of their microenvironment. In our recent
      studies, we have observed that oral, pancreatic, and melanoma CSCs were capable
      of forming large tumors in humanized bone marrow, liver, thymus (hu-BLT) mice
      with fully reconstituted human immune system. In addition, major human immune
      subsets including NK cells, T cells, B cells, and monocytes were present in the
      spleen, bone marrow, peripheral blood, and tumor microenvironment. Similar to our
      previously published in vitro data, CSCs differentiated with split anergized NK
      cells prior to implantation in mice formed smaller tumors. Intravenous injection
      of functionally potent osteoclast-expanded NK cells inhibited tumor growth
      through differentiation of CSCs in humanized mice. In this review, we present
      current approaches, advances, and existing limitations in studying interactions
      of the immune system with the tumor, in particular NK cells with CSCs, using in
      vivo preclinical hu-BLT mouse model. In addition, we discuss the use of
      osteoclast-expanded NK cells in targeting cancer stem-like tumors in humanized
      mice-a strategy that provides a much-needed platform to develop effective cancer
      immunotherapies.

PMID- 27034237
TI  - Concomitant posterior cruciate ligament injuries with direct injury-related
      patellar fractures.
AB  - INTRODUCTION: Posterior cruciate ligament (PCL) injuries and direct injury
      related patellar fractures have similar causative factors. However, the
      mechanisms underlying these injuries differ. We aimed to evaluate the incidence
      and relationship between PCL injuries and direct injury-related patellar
      fractures. MATERIALS AND METHODS: Of the 195 patients diagnosed with a patellar
      fracture at our clinic during 2007-2011, 104 required surgical treatment and
      underwent the posterior drawer test under general anesthesia and magnetic
      resonance imaging. We assessed whether the causes of trauma, fracture
      classification, compression of the fracture fragment, and fracture displacement
      were related to the incidence of PCL injuries. RESULTS: Of the 104 patients, 26
      had concomitant PCL injuries with direct injury-related patellar fractures. Most
      of the PCL injuries were grades 1 and 2, observed in 14 and 9 patients,
      respectively. Among three patients with grade 3 PCL injury, only two required PCL
      reconstruction. No significant relationship was observed between the causes of
      trauma and the incidence of PCL injury. According to the fracture classification,
      lower pole and comminuted fractures were associated with higher incidence rates
      of PCL injury than transverse and vertical fractures. Compressed and displaced
      patellar fractures were also associated with higher incidence rates of PCL
      injury. CONCLUSION: Although a PCL injury requiring surgical intervention was
      extremely rare, 25 % patients who required surgery for patellar fractures
      presented with a PCL injury. The incidence of a PCL injury was higher in the
      lower pole, comminuted, displaced, and compressed patellar fractures.

PMID- 27034238
TI  - Erratum to: A novel approach for the development of tiered use biological
      criteria for rivers and streams in an ecologically diverse landscape.

PMID- 27034242
TI  - Bioactivity and Mechanical Stability of 45S5 Bioactive Glass Scaffolds Based on
      Natural Marine Sponges.
AB  - Bioactive glass (BG) based scaffolds (45S5 BG composition) were developed by the
      replica technique using natural marine sponges as sacrificial templates. The
      resulting scaffolds were characterized by superior mechanical properties
      (compression strength up to 4 MPa) compared to conventional BG scaffolds prepared
      using polyurethane (PU) packaging foam as a template. This result was ascribed to
      a reduction of the total scaffold porosity without affecting the pore
      interconnectivity (>99%). It was demonstrated that the reduction of total
      porosity did not affect the bioactivity of the BG-based scaffolds, tested by
      immersion of scaffolds in simulated body fluid (SBF). After 1 day of immersion in
      SBF, a homogeneous CaP deposit on the surface of the scaffolds was formed, which
      evolved over time into carbonate hydroxyapatite (HCA). Moreover, the enhanced
      mechanical properties of these scaffolds were constant over time in SBF; after an
      initial reduction of the maximum compressive strength upon 7 days of immersion in
      SBF (to 1.2 +/- 0.2 MPa), the strength values remained almost constant and higher
      than those of BG-based scaffolds prepared using PU foam (<0.05 MPa). Preliminary
      cell culture tests with Saos-2 osteoblast cell line, namely direct and indirect
      tests, demonstrated that no toxic residues remained from the natural marine
      sponge templates and that cells were able to proliferate on the scaffold
      surfaces.

PMID- 27034243
TI  - Bell's palsy syndrome: mimics and chameleons.
AB  - In this article we will explore the mimics and chameleons of Bell's palsy and in
      addition argue that we should use the term 'Bell's palsy syndrome' to help guide
      clinical reasoning when thinking about patients with facial weakness. The
      diagnosis of Bell's palsy can usually be made on clinical grounds without the
      need for further investigations. This is because the diagnosis is not one of
      exclusion (despite this being commonly how it is described), a lower motor
      neurone facial weakness where all alternative causes have been eliminated, but
      rather a positive recognition of a clinical syndrome, with a number of
      exclusions, which are described below. This perhaps would be more accurately
      referred to a 'Bell's palsy syndrome'. Treatment with corticosteroids improves
      outcome; adding an antiviral probably reduces the rates of long-term
      complications.

PMID- 27034244
TI  - The Impact of Different DCE-Based Approaches When Anchoring Utility Scores.
AB  - BACKGROUND: Discrete choice experiments (DCEs) have been proposed as a method to
      estimate utility weights for health states within utility instruments. However,
      the most appropriate method to anchor the utility values on the full health to
      dead quality-adjusted life year (QALY) scale remains uncertain. We test four
      approaches to anchoring in which dead is valued at zero and full health at one.
      METHODS: We use data from two DCEs valuing EQ-5D-3L and EQ-5D-5L health states,
      which presented pairs of health profiles with an associated duration, and a dead
      option. The approaches to anchoring the results on the required scale were (1)
      using only preferences between non-dead health profiles; (2) including the dead
      data, treating it as a health profile with zero duration; (3) explicitly
      modelling both duration and dead; and (4) using the preferences regarding the
      dead health state as an external anchor subsequent to the estimation of approach
      1. RESULTS: All approaches lead to differences in the scale of utility
      decrements, but not the ranking of EQ-5D health states. The models differ in
      their ability to predict preferences around dead health states, and the
      characteristics of the value sets in terms of their range and the proportion of
      states valued as worse than dead. DISCUSSION: Appropriate anchoring of DCEs with
      or without complementary time trade-off (TTO) data remains unresolved, and the
      method chosen will impact on health resource allocation decision making employing
      the value sets.

PMID- 27034245
TI  - Identifying and Revealing the Importance of Decision-Making Criteria for Health
      Technology Assessment: A Retrospective Analysis of Reimbursement Recommendations
      in Ireland.
AB  - BACKGROUND: Decisions on reimbursement of health interventions in many
      jurisdictions are informed by health technology assessments (HTAs). Historically,
      the focus of these has often been cost effectiveness or cost utility, while other
      criteria were considered informally. More recently, there has been an increasing
      interest in the formal incorporation of additional criteria using multi-criteria
      decision analysis. Such an approach has not yet formally been part of decision
      making policy in Ireland. OBJECTIVE: The objective of this analysis is to
      demonstrate that cost effectiveness is not the only criterion influencing
      reimbursement decisions in Ireland. Furthermore, the aim is to reveal criteria
      that may have informally influenced reimbursement decisions in the past. METHODS:
      A list of potential criteria was identified based on the literature, national
      guidelines and experience of the national HTA agency. Information on each of
      these criteria was sought for every assessment conducted in Ireland up to July
      2015. A logistic regression was fitted to the data to identify influential
      parameters. Model selection was performed using the Bolasso method. RESULTS:
      Thirteen criteria were considered in the analysis. Two members of the HTA review
      team assessed the performance of the interventions against these criteria. Model
      selection suggests that the incremental cost-effectiveness ratio and quality of
      evidence could be important drivers of reimbursement recommendations in Ireland.
      Less important drivers suggested include the year of assessment, the level of
      uncertainty, as well as safety and tolerability. CONCLUSION: The analysis
      demonstrates that recommendations for or against the reimbursement of
      technologies in Ireland are not only driven by cost effectiveness. This
      highlights the need for more formal inclusion of criteria in the process, to
      improve transparency and ensure consistency.

PMID- 27034246
TI  - Biomonitoring of the mycotoxin Zearalenone: current state-of-the art and
      application to human exposure assessment.
AB  - Zearalenone (ZEN), a mycotoxin with high estrogenic activity in vitro and in
      vivo, is a widespread food contaminant that is commonly detected in maize, wheat,
      barley, sorghum, rye and other grains. Human exposure estimates based on
      analytical data on ZEN occurrence in various food categories and food consumption
      data suggest that human exposure to ZEN and modified forms of ZEN may be close to
      or even exceed the tolerable daily intake (TDI) derived by the European Food
      Safety Authority (EFSA) for some consumer groups. Considering the inherent
      uncertainties in estimating dietary intake of ZEN that may lead to an under- or
      overestimation of ZEN exposure and consequently human risk and current lack of
      data on vulnerable consumer groups, there is a clear need for more comprehensive
      and reliable exposure data to refine ZEN risk assessment. Human biomonitoring
      (HBM) is increasingly being recognized as an efficient and cost-effective way of
      assessing human exposure to food contaminants, including mycotoxins. Based on
      animal and (limited) human data on the toxicokinetics of ZEN, it appears that
      excretion of ZEN and its major metabolites may present suitable biomarkers of ZEN
      exposure. In view of the limitations of available dietary exposure data on ZEN
      and its modified forms, the purpose of this review is to provide an overview of
      recent studies utilizing HBM to monitor and assess human exposure to ZEN.
      Considerations are given to animal and human toxicokinetic data relevant to HBM,
      analytical methods, and available HBM data on urinary biomarkers of ZEN exposure
      in different cohorts. 

PMID- 27034247
TI  - The HA-incorporated nanostructure of a peptide-drug amphiphile for targeted
      anticancer drug delivery.
AB  - A simple peptide based prodrug of camptothecin (CPT) has been synthesised in
      which the CPT is conjugated to a tripeptide (KCK) via a disulfide linkage (KCK
      CPT) and self-assembled into well-defined nanostructures in water depending on
      the concentration. The hyaluronic acid (HA) complex of KCK-CPT exhibited target
      specific toxicity with excellent antitumour efficiency. 

PMID- 27034248
TI  - Prebiotics and age, but not probiotics affect the transformation of 2-amino-3
      methyl-3H-imidazo[4,5-f]quinoline (IQ) by fecal microbiota - An in vitro study.
AB  - Heterocyclic aromatic amines (HAAs) are carcinogens which are formed in meat
      cooked using high-temperature methods. The human gastrointestinal (GI) microbiota
      plays a crucial role in maintaining health in humans of different ages, and
      especially in the elderly. However, the GI microbiota, whose metabolism and
      composition changes with age, may also be responsible for the activation of
      mutagenic substances reaching the colon with diet. Probiotics and prebiotics are
      promising in terms of reducing the destructive effects of HAAs. The aim of the
      study was to determine if fecal microbiota derived from the feces of 27
      volunteers: infants (up to 18 months), adults (aged 23-39 years), the sub-elderly
      (aged 64-65 years), and the elderly (aged 76-87 years), and the presence of
      probiotics or prebiotics, affected the transformation of IQ (2-amino-3
      methylimidazo[4,5-f]quinoline) to 7-OH-IQ (2-amino-3,6-dihydro-3-methyl-7H
      imidazo[4,5-f]quinoline-7-one). The compounds were identified using LC-MS(n),
      NMR, and FTIR. Their genotoxicity was compared in the comet assay. Individual
      strains capable of IQ transformation were also identified. 7-OH-IQ was detected
      in six persons (two children and four elderly individuals). The degree of IQ
      conversion ranged from 26% (4-month-old girl) to 94% (81-year-old woman) of the
      initial quantity. Four Enterococcus isolates: two Enterococcus faecium and two
      Enterococcus faecalis strains, as well as one Clostridium difficile strain (LOCK
      1030, from the culture collection) converted IQ to 7-OH-IQ. The genotoxicity of
      samples containing 7-OH-IQ was even three times higher (P < 0.05) than those with
      IQ and was correlated with the degree of IQ conversion and 7-OH-IQ concentration.

PMID- 27034249
TI  - Mild decrease in TBX20 promoter activity is a potentially protective factor
      against congenital heart defects in the Han Chinese population.
AB  - Congenital heart defects (CHDs) are one of the most common human birth defects
      worldwide. TBX20 is a crucial transcription factor for the development of
      embryonic cardiovascular system. Previous studies have demonstrated that
      mutations in the TBX20 coding region contribute to familial and sporadic CHD
      occurrence. However, it remains largely unknown whether variants in the TBX20
      regulatory region are also related to CHDs. In this study, we sequenced the 2 kb
      region upstream of the TBX20 transcription start site in 228 CHD patients and 292
      controls in a Han Chinese population. Among the 8 single nucleotide polymorphisms
      (SNPs) identified, six SNPs are in strong linkage disequilibrium and the minor
      alleles are associated with lower CHD risk (for rs10235849 chosen as tag SNP, p =
      0.0069, OR (95% CI) = 0.68 (0.51-0.90)). Functional analysis showed that the
      minor alleles have lower transcriptional activity than major alleles in both
      human heart tissues and three cell lines. The electrophoretic mobility shift
      assay suggested that TBX20 minor alleles may exhibit higher binding affinity with
      certain transcription repressors. Our results indicate that a moderately lower
      TBX20 activity potentially reduces CHD risk in the Han Chinese population,
      providing new insight in the study of CHD etiology. 

PMID- 27034250
TI  - Blood-brain barrier breakdown promotes macrophage infiltration and cognitive
      impairment in leptin receptor-deficient mice.
AB  - Accumulating evidence indicates that obesity accelerates the onset of cognitive
      decline. While mechanisms are still being identified, obesity promotes peripheral
      inflammation and increases blood-brain barrier (BBB) permeability. However, no
      studies have manipulated vascular permeability in obesity to determine whether
      BBB breakdown underlies memory deficits. Protein kinase Cbeta (PKCbeta)
      activation destabilizes the BBB, and we used a PKCbeta inhibitor (Enzastaurin) to
      block BBB leakiness in leptin receptor-deficient (db/db) mice. Enzastaurin
      reversed BBB breakdown in db/db mice and normalized hippocampal function without
      affecting obesity or metabolism. Flow cytometric analysis of forebrain
      mononuclear cells (FMCs) from db/db mice revealed macrophage infiltration and
      induction of the activation marker MHCII in microglia and macrophages.
      Enzastaurin eliminated macrophage infiltration and MHCII induction, and protein
      array profiling revealed parallel reductions in IL1beta, IL6, MCP1, and TNFalpha.
      To investigate whether these signals attract peripheral monocytes, FMCs from Wt
      and db/db mice were plated below migration inserts containing peritoneal
      macrophages. Peritoneal macrophages from db/db mice exhibit increases in
      transmigration that were blocked by recombinant IL1RA. These studies indicate
      that BBB breakdown impairs cognition in obesity and diabetes by allowing
      macrophage infiltration, with a potential role for IL1beta in trafficking of
      peripheral monocytes into the brain.

PMID- 27034251
TI  - Hepatic venous pressure gradient for preoperative assessment of patients with
      resectable hepatocellular carcinoma: A comment for moving forward.

PMID- 27034252
TI  - Update on alpha-1 antitrypsin deficiency: New therapies.
AB  - alpha1-Antitrypsin deficiency is characterised by the misfolding and
      intracellular polymerisation of mutant alpha1-antitrypsin within the endoplasmic
      reticulum of hepatocytes. The retention of mutant protein causes hepatic damage
      and cirrhosis whilst the lack of an important circulating protease inhibitor
      predisposes the individuals with severe alpha1-antitrypsin deficiency to early
      onset emphysema. Our work over the past 25years has led to new paradigms for the
      liver and lung disease associated with alpha1-antitrypsin deficiency. We review
      here the molecular pathology of the cirrhosis and emphysema associated with
      alpha1-antitrypsin deficiency and show how an understanding of this condition
      provided the paradigm for a wider group of disorders that we have termed the
      serpinopathies. The detailed understanding of the pathobiology of alpha1
      antitrypsin deficiency has identified important disease mechanisms to target. As
      a result, several novel parallel and complementary therapeutic approaches are in
      development with some now in clinical trials. We provide an overview of these new
      therapies for the liver and lung disease associated with alpha1-antitrypsin
      deficiency.

PMID- 27034253
TI  - HBcrAg predicts hepatocellular carcinoma development: An analysis using time
      dependent receiver operating characteristics.
AB  - BACKGROUND & AIMS: Several hepatitis B virus (HBV) markers have been identified
      as factors associated with the development of hepatocellular carcinoma (HCC) in
      patients with chronic hepatitis B (CHB). We clarified the predictive power of HBV
      markers for the development of HCC using receiver operating characteristic (ROC)
      analysis with a consideration of time dependence. METHODS: A total of 1031 CHB
      patients who were not treated with nucleos(t)ide analogue therapy were enrolled.
      Univariate, multivariate, and time-dependent ROC curves for HBV markers
      associated with the development of HCC were analyzed. RESULTS: Seventy-eight
      patients developed HCC during the follow-up period (median duration 10.7years).
      Different levels or statuses of several HBV markers (HBV genotype, HBV DNA, HBV
      core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), and basal core
      promoter (BCP)), but not hepatitis B surface antigen, were significantly
      associated with the incidence of HCC by univariate analysis using the log-rank
      test. Cox proportional hazards models using the covariates of HBV genotype
      status, HBV DNA levels, HBcrAg levels, HBeAg status, and BCP status indicated
      that HBcrAg >2.9logU/ml (hazard ratio (HR), 5.05; 95% confidence interval (CI),
      2.40-10.63) and BCP mutation (HR, 28.85; 95% CI, 4.00-208.20) were independently
      associated with the incidence of HCC. Additionally, time-dependent ROC analysis
      showed that HBcrAg was superior to HBV DNA in terms of predictive power for HCC
      development throughout the follow-up period. CONCLUSIONS: Elevation of HBcrAg
      levels in CHB patients is associated with the development of HCC. HBcrAg is an
      excellent predictor of HCC development. LAY SUMMARY: Hepatitis B virus (HBV) core
      related antigen (HBcrAg) is an excellent predictor of hepatocellular carcinoma
      (HCC) development in chronic hepatitis B patients without nucleos(t)ide analogue
      therapy. HBcrAg was superior to HBV DNA in terms of predictive power for HCC
      development by time-dependent receiver operating characteristic analysis.

PMID- 27034254
TI  - BMA launches judicial review against contract imposition.

PMID- 27034255
TI  - Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional
      Boiling Surfaces.
AB  - Bubble nucleation control, growth and departure dynamics is important in
      understanding boiling phenomena and enhancing nucleate boiling heat transfer
      performance. We report a novel bi-functional heterogeneous surface structure that
      is capable of tuning bubble nucleation, growth and departure dynamics. For the
      fabrication of the surface, hydrophobic polymer dot arrays are first printed on a
      substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor
      assisted nanomaterial deposition (MAND) processing. Wettability contrast between
      the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the
      fabrication of heterogeneous surfaces with distinct wettability regions.
      Heterogeneous surfaces with various configurations were fabricated and their
      bubble dynamics were examined at elevated heat flux, revealing various nucleate
      boiling phenomena. In particular, aligned and patterned bubbles with a tunable
      departure frequency and diameter were demonstrated in a boiling experiment for
      the first time. Taking advantage of our fabrication method, a 6 inch wafer size
      heterogeneous surface was prepared. Pool boiling experiments were also performed
      to demonstrate a heat flux enhancement up to 3X at the same surface superheat
      using bi-functional surfaces, compared to a bare stainless steel surface. 

PMID- 27034256
TI  - Formation of calcium sulfate through the aggregation of sub-3 nanometre primary
      species.
AB  - The formation pathways of gypsum remain uncertain. Here, using truly in situ and
      fast time-resolved small-angle X-ray scattering, we quantify the four-stage
      solution-based nucleation and growth of gypsum (CaSO4.2H2O), an important mineral
      phase on Earth and Mars. The reaction starts through the fast formation of well
      defined, primary species of <3 nm in length (stage I), followed in stage II by
      their arrangement into domains. The variations in volume fractions and electron
      densities suggest that these fast forming primary species contain Ca-SO4-cores
      that self-assemble in stage III into large aggregates. Within the aggregates
      these well-defined primary species start to grow (stage IV), and fully crystalize
      into gypsum through a structural rearrangement. Our results allow for a
      quantitative understanding of how natural calcium sulfate deposits may form on
      Earth and how a terrestrially unstable phase-like bassanite can persist at low
      water activities currently dominating the surface of Mars. 

PMID- 27034257
TI  - Circular polarization sensitive absorbers based on graphene.
AB  - It is well known that the polarization of a linearly polarized (LP) light would
      rotate after passing through a single layer graphene under the bias of a
      perpendicular magnetostatic field. Here we show that a corresponding phase shift
      could be expected for circularly polarized (CP) light, which can be engineered to
      design the circular polarization sensitive devices. We theoretically validate
      that an ultrathin graphene-based absorber with the thickness about lambda/76 can
      be obtained, which shows efficient absorption >90% within incident angles of +/
      80 degrees . The angle-independent phase shift produced by the graphene is
      responsible for the nearly omnidirectional absorber. Furthermore, a broadband
      absorber in frequencies ranging from 2.343 to 5.885 THz with absorption over 90%
      is designed by engineering the dispersion of graphene. 

PMID- 27034258
TI  - Crowdsourcing reproducible seizure forecasting in human and canine epilepsy.
AB  - SEE MORMANN AND ANDRZEJAK DOI101093/BRAIN/AWW091 FOR A SCIENTIFIC COMMENTARY ON
      THIS ARTICLE  : Accurate forecasting of epileptic seizures has the potential to
      transform clinical epilepsy care. However, progress toward reliable seizure
      forecasting has been hampered by lack of open access to long duration recordings
      with an adequate number of seizures for investigators to rigorously compare
      algorithms and results. A seizure forecasting competition was conducted on
      kaggle.com using open access chronic ambulatory intracranial
      electroencephalography from five canines with naturally occurring epilepsy and
      two humans undergoing prolonged wide bandwidth intracranial
      electroencephalographic monitoring. Data were provided to participants as 10-min
      interictal and preictal clips, with approximately half of the 60 GB data bundle
      labelled (interictal/preictal) for algorithm training and half unlabelled for
      evaluation. The contestants developed custom algorithms and uploaded their
      classifications (interictal/preictal) for the unknown testing data, and a
      randomly selected 40% of data segments were scored and results broadcasted on a
      public leader board. The contest ran from August to November 2014, and 654
      participants submitted 17 856 classifications of the unlabelled test data. The
      top performing entry scored 0.84 area under the classification curve. Following
      the contest, additional held-out unlabelled data clips were provided to the top
      10 participants and they submitted classifications for the new unseen data. The
      resulting area under the classification curves were well above chance
      forecasting, but did show a mean 6.54 +/- 2.45% (min, max: 0.30, 20.2) decline in
      performance. The kaggle.com model using open access data and algorithms generated
      reproducible research that advanced seizure forecasting. The overall performance
      from multiple contestants on unseen data was better than a random predictor, and
      demonstrates the feasibility of seizure forecasting in canine and human
      epilepsy.media-1vid110.1093/brain/aww045_video_abstractaww045_video_abstract.

PMID- 27034259
TI  - Amino Compounds as Inhibitors of De Novo Synthesis of Chlorobenzenes.
AB  - The inhibitory effects of four amino compounds on the formation of chlorobenzenes
      (CBzs)--dioxin precursors and indicators, and the inhibitory mechanisms were
      explored. The results show NH4H2PO4 can decrease the total yields of CBzs (1,2di
      CBz, 1,3di-CBz, 1,4di-CBz, penta-CBz and hexa-CBz) by 98.1%+/-1.6% and 96.1%+/
      0.7% under air and nitrogen flow. The inhibitory effects indicated by the total
      yields of CBzs follow the order NH4H2PO4 > NH4HF2 > (NH4)2SO4 > NH4Br under air
      flow and NH4H2PO4 ~ (NH4)2SO4 ~ NH4HF2 >NH4Br under nitrogen flow. The inhibition
      mechanism revealed by thermal analysis that CuCl2 was converted to CuPO3 by
      reacting with NH4H2PO4 below 200  degrees C, which can block the transfer of
      chlorine and formation of C-Cl bonds at 350  degrees C. The effects of the other
      three inhibitors were weaker because their reactions with CuCl2, which form other
      copper compounds, and the reaction of CuCl2 with carbon, which forms C-Cl bonds,
      were almost simultaneous and competitive. Oxygen influenced the yield of CBzs
      obviously, and the total yield of five CBzs sharply increased with oxygen.
      Because of their high efficiency, low environmental impact, low cost, and
      availability, amino compounds--especially NH4H2PO4--can be utilized as inhibitors
      of CBzs during incineration.

PMID- 27034260
TI  - Breast and prostate cancer survivors' experiences of patient-centered cancer
      follow-up care from primary care physicians and oncologists.
AB  - PURPOSE: Patient-physician relationships impact health care seeking and
      preventive screening behaviors among patients. At the end of active treatment
      some cancer survivors report feeling disconnected from their care team. This
      study explores cancer survivors' experiences of patient-centered cancer follow-up
      care provided by primary care physicians (PCP) and oncologists (ONC). METHODS:
      Three hundred five early stage, breast and prostate cancer survivors at least 2
      years post treatment were surveyed from four community hospital oncology programs
      in New Jersey. Participants reported receipt of patient-centered care measured by
      care coordination, comprehensiveness of care, and personal relationship with PCPs
      and ONCs. RESULTS: PCPs received higher ratings for coordination of care and
      comprehensive care than ONCs from all survivors (P < 0.01). However, prostate and
      breast cancer survivors rated strengths of their personal bonds with the
      physicians differently. While prostate cancer survivors rated PCPs significantly
      higher for all items (P < 0.028), breast cancer survivors rated ONCs
      significantly higher on four out of seven items including having been through a
      lot together, understanding what is important regarding health, knowing their
      medical history and taking their beliefs and wishes into account (P < 0.036).
      CONCLUSIONS: Prostate and breast cancer survivors report different experiences
      with their PCPs and oncologists around the comprehensiveness and coordination of
      their cancer follow-up care in addition to the strength of their relationships
      with their physicians. IMPLICATIONS FOR CANCER SURVIVORS: There are important
      differences in the experience of patient-centered care among cancer survivors
      that should be considered when planning care models and interventions for these
      different populations.

PMID- 27034261
TI  - Wnt-11 overexpression promoting the invasion of cervical cancer cells.
AB  - Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a
      crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has
      not been well investigated. The aim of this study was to investigate the role of
      Wnt-11 in cervical tumor proliferation and invasion. This study examined 24
      normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN),
      and 78 cervical cancer samples. The expression of Wnt-11 was investigated by
      immunohistochemistry and quantitative reverse transcription-polymerase chain
      reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV)
      E6 oncoprotein was also investigated by immunohistochemistry. In addition, the
      expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and beta
      catenin was examined by western blot analysis following Wnt-11 knockdown or
      overexpression in HeLa or SiHa cells, respectively. The promotion of cervical
      cancer cell proliferation and invasion was investigated using the cell counting
      kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression
      increased in a manner that corresponded with the progression of cervical cancer
      and was significantly correlated with the International Federation of Gynecology
      and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV
      infection. Wnt-11 protein expression was positively associated with HR-HPV E6
      protein expression in all 78 cervical cancer samples (P < 0.001). Furthermore,
      Wnt-11 was positively associated with P-JNK1 expression and promoted cervical
      cancer cell proliferation and invasion. These observations suggest that the
      increased Wnt-11 expression observed in cervical cancer cells may lead to the
      phosphorylation and activation of JNK-1 and significantly promote tumor cell
      proliferation and cell migration/invasion through activation of the Wnt/JNK
      pathway. Consequently, Wnt-11 may serve as a novel target for cervical cancer
      therapy.

PMID- 27034262
TI  - The roles of serum PDCD5 in circulating CD133 positive cells of the patients with
      gastric cancer.
AB  - Cancer stem cells are responsible for the development, metastasis, recurrence,
      and drug resistance of cancer. More and more studies exhibited that the
      circulating CD133+ cells is a marker for the prognosis of various malignancies.
      Programmed cell death protein 5 (PDCD5) can promote apoptosis in different tumor
      cell types in response to various stimuli. However, the impact of PDCD5 on
      circulating CD133+ cells of gastric cancer patients remains unclear. In this
      study, we detected serum PDCD5 level in blood samples of the patients with
      gastric cancer by using ELISA. MTT assay, sphere assay, and wound healing assay
      were used to test the anti-tumor effects of rhPDCD5 on CD133+ cells in vitro.
      Lower serum levels of PDCD5 protein were identified in the gastric cancer
      patients that with CD133+ fraction more than 1.6 %. No difference between healthy
      controls and the gastric cancer patients that with CD133+ fraction less than 1.6
      %. Serum PDCD5 was correlated with the favorable prognosis of patients with
      gastric cancer. In the last, we confirmed that rhPDCD5 could induce apoptosis,
      and inhibit the proliferation, colony formation, and mobility of CD133+ cells in
      vitro by suppressing MEK/ERK pathway. Serum PDCD5 could be considered as a
      potential drug for the gastric cancer patients with circulating CD133+ cells.

PMID- 27034263
TI  - BRAF mutation may have different prognostic implications in early- and late-stage
      colorectal cancer.
AB  - The prognostic implication of BRAF mutant colorectal cancer remains paradoxical.
      Records of BRAF mutant and wild-type colorectal cancer patients at all stages
      were reviewed. Clinicopathologic features, including microsatellite instability,
      CpG islands methylator phenotype, and overall survival, of these patients were
      analyzed. Between 2005 and 2013, 428 colorectal cancer patients were enrolled in
      this study. The overall survival between BRAF mutant and wild-type patients with
      early-stage (stages I and II) colorectal cancer differed nonsignificantly (P =
      0.99). By contrast, in late-stage (stages III and IV) patients, the median
      overall survival of BRAF mutant patients (N = 25) was significantly poorer than
      that of BRAF wild-type (N = 207) patients (BRAF mutant: 21.3 months (95%
      confidence interval [CI] 7.1-35.5); BRAF wild-type: 53.5 months (95% CI 37.5
      69.5), P < 0.0001). In early-stage patients, we found that BRAF mutation was
      significantly associated with CpG island methylator phenotype-positive (P <
      0.001), and microsatellite instability-high status (P = 0.0013). Conversely, in
      late-stage patients, BRAF mutation was significantly associated with CpG island
      methylator phenotype-positive (P = 0.0015) and the right-side colon (P = 0.014).
      BRAF mutation may have different prognostic implications in early- and late-stage
      colorectal cancer.

PMID- 27034264
TI  - Cyclin D1 and cyclin E2 are differentially expressed in gastric cancer.
AB  - Cell cycle regulators cyclin D1 and cyclin E2 function in G1/S transition by
      activating downstream cyclin-dependent kinases. Deregulated expression of these
      cyclins has been reported in various cancers. However, little is known about
      their clinical significance in gastric carcinoma. We aimed to explore that
      whether there is differential expression of these cyclins in clinically distinct
      gastric cancer patients. In this study we recruited a total of 92 subjects
      including 20 controls and 72 cases of histopathologically proven gastric
      carcinoma. Expression profiling at transcript level was done by semiquantitative
      RT-PCR and of protein by immunohistochemistry. Receiver operator characteristics
      analysis was done for determining diagnostic utility of cyclin D1 and cyclin E2.
      We demonstrate that cyclins D1 and E2 are frequently overexpressed in early
      stages of gastric carcinoma. Interestingly, expression of cyclins D1 and E2
      significantly correlates with different clinical parameters such as gender,
      histological type (intestinal and diffuse), tumor location (proximal, middle, and
      distal), tumor differentiation (differentiated and undifferentiated), tumor
      invasion (serosal, lymphatic, and venous) and tumor metastasis (lymph node,
      peritoneal, ascites, and liver). Cyclin D1 has significantly higher sensitivity
      and specificity as diagnostic biomarker than cyclin E2. Our results suggest that
      overexpression of cyclin D1 and cyclin E2 is an early event in gastric
      carcinogenesis. The differential expression of these cyclins may be useful as
      diagnostic biomarkers for early detection of gastric carcinoma. 

PMID- 27034265
TI  - Clinical significance of circulating miRNA detection in lung cancer.
AB  - Lung cancer is the most common cancer in the world and the leading cause of tumor
      death among males. MicroRNAs (miRNAs) are single-stranded RNAs of approximately
      22 nucleotides and constituted a new class of gene regulators in humans. As a
      novel class of emerging biomarkers, the aberrant expression of miRNA has been
      detected in various tumors. miRNAs are secreted into circulation by microvesicles
      from the broken tumor cells and act as either oncogenes or tumor suppressors in
      tumor tissues. In this review, we summarized different circulating miRNAs and
      their expression level as well as predictable values in lung cancer patients
      which were investigated in recent 5 years. Circulating miRNAs are found to be
      dysregulated and have association with clinicopathological parameters and overall
      survival in lung cancer patients. In conclusion, circulating miRNAs have the
      potential for distinguishing lung cancer patients from healthy individuals, with
      the advantages of stabilities, noninvasiveness and cost-effectiveness. 

PMID- 27034266
TI  - Losses of leaf area owing to herbivory and early senescence in three tree species
      along a winter temperature gradient.
AB  - In temperate climates, evergreen leaves have to survive throughout low
      temperature winter periods. Freezing and chilling injuries can lead to
      accelerated senescence of part of the leaf surface, which contributes to a
      reduction of the lifespan of the photosynthetic machinery and of leaf lifetime
      carbon gain. Low temperatures are also associated with changes in foliar
      chemistry and morphology that affect consumption by herbivores. Therefore, the
      severity of foliar area losses caused by accelerated senescence and herbivory can
      change along winter temperature gradients. The aim of this study is to analyse
      such responses in the leaves of three evergreen species (Quercus ilex, Q. suber
      and Pinus pinaster) along a climatic gradient. The leaves of all three species
      presented increased leaf mass per area (LMA) and higher concentrations of
      structural carbohydrates in cooler areas. Only the two oak species showed visible
      symptoms of damage caused by herbivory, this being less intense at the coldest
      sites. The leaves of all three species presented chlorotic and necrotic spots
      that increased in size with leaf age. The foliar surface affected by chlorosis
      and necrosis was larger at the sites with the coldest winters. Therefore, the
      effects of the winter cold on the lifespan of the photosynthetic machinery were
      contradictory: losses of leaf area due to accelerated senescence increased, but
      there was a decrease in losses caused by herbivory. The final consequences for
      carbon assimilation strongly depend on the exact timing of the appearance of the
      damage resulting from low temperature and grazing by herbivores.

PMID- 27034267
TI  - Generation of chickens expressing Cre recombinase.
AB  - Cre recombinase has been extensively used for genome engineering in transgenic
      mice yet its use in other species has been more limited. Here we describe the
      generation of transgenic chickens expressing Cre recombinase. Green fluorescent
      protein (GFP)-positive chicken primordial germ cells were stably transfected with
      beta-actin-Cre-recombinase using phiC31 integrase and transgenic chickens were
      generated. Cre recombinase activity was verified by mating Cre birds to birds
      carrying a floxed transgene. Floxed sequences were only excised in offspring from
      roosters that inherited the Cre recombinase but were excised in all offspring
      from hens carrying the Cre recombinase irrespective of the presence of the Cre
      transgene. The Cre recombinase transgenic birds were healthy and reproductively
      normal. The Cre and GFP genes in two of the lines were closely linked whereas the
      genes segregated independently in a third line. These founders allowed
      development of GFP-expressing and non-GFP-expressing Cre recombinase lines. These
      lines of birds create a myriad of opportunities to study developmentally
      regulated and tissue-specific expression of transgenes in chickens.

PMID- 27034268
TI  - Imbalance in chemical space: How to facilitate the identification of protein
      protein interaction inhibitors.
AB  - Protein-protein interactions (PPIs) play vital roles in life and provide new
      opportunities for therapeutic interventions. In this large data analysis, 3,300
      inhibitors of PPIs (iPPIs) were compared to 17 reference datasets of collectively
      ~566,000 compounds (including natural compounds, existing drugs, active compounds
      on conventional targets, etc.) using a chemoinformatics approach. Using this
      procedure, we showed that comparable classes of PPI targets can be formed using
      either the similarity of their ligands or the shared properties of their binding
      cavities, constituting a proof-of-concept that not only can binding pockets be
      used to group PPI targets, but that these pockets certainly condition the
      properties of their corresponding ligands. These results demonstrate that
      matching regions in both chemical space and target space can be found. Such
      identified classes of targets could lead to the design of PPI-class-specific
      chemical libraries and therefore facilitate the development of iPPIs to the stage
      of drug candidates. 

PMID- 27034269
TI  - No Static at All: Tuning Into the Complexities of Ca2+ Signaling in the
      Endothelium.

PMID- 27034270
TI  - Widespread Intracoronary Cardiopoietic Cell Infusion: Treating at the Time of
      Myocardial Reperfusion to Prevent Rather Than Reverse Established Left
      Ventricular Dysfunction Moves Us Closer to Practical Clinical Translation.

PMID- 27034271
TI  - GRK2 in Lymphocytes: Expanding the Arsenal of Heart Failure Prognostics.

PMID- 27034272
TI  - Remote Ischemic Conditioning and the Long Road to Clinical Translation: Lessons
      Learned From ERICCA and RIPHeart.

PMID- 27034273
TI  - Remote Ischemic Preconditioning for Cardiac Surgery: Reflections on Evidence of
      Efficacy.

PMID- 27034274
TI  - Duchenne Muscular Dystrophy Mice and Men: Can Understanding a Genetic
      Cardiomyopathy Inform Treatment of Other Myocardial Diseases?

PMID- 27034276
TI  - Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent
      Muscle Defects?
AB  - This "Controversies in Cardiovascular Research" article evaluates the evidence
      for and against the hypothesis that the circulating blood level of growth
      differentiation factor 11 (GDF11) decreases in old age and that restoring normal
      GDF11 levels in old animals rejuvenates their skeletal muscle and reverses
      pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the
      original GDF11 hypothesis in skeletal and cardiac muscle have not been validated
      by several independent groups. These new studies have either found no effects of
      restoring normal GDF11 levels on cardiac structure and function or have shown
      that increasing GDF11 or its closely related family member growth differentiation
      factor 8 actually impairs skeletal muscle repair in old animals. One possible
      explanation for what seems to be mutually exclusive findings is that the original
      reagent used to measure GDF11 levels also detected many other molecules so that
      age-dependent changes in GDF11 are still not well known. The more important issue
      is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age
      related cardiac pathologies. There are substantial new and existing data showing
      that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old
      animals. There is also new evidence disputing the idea that there is pathological
      hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac
      pathologies. Finally, high [GDF11] causes reductions in body and heart weight in
      both young and old animals, suggestive of a cachexia effect. Our conclusion is
      that elevating blood levels of GDF11 in the aged might cause more harm than good.

PMID- 27034275
TI  - Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and
      Questions for Future Investigation.
AB  - Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely
      related members of the transforming growth factor beta superfamily and are often
      perceived to serve similar or overlapping roles. Yet, despite commonalities in
      protein sequence, receptor utilization and signaling, accumulating evidence
      suggests that these 2 ligands can have distinct functions in many situations.
      GDF11 is essential for mammalian development and has been suggested to regulate
      aging of multiple tissues, whereas myostatin is a well-described negative
      regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic
      processes. In this review, we discuss the biochemical regulation of GDF11 and
      myostatin and their functions in the heart, skeletal muscle, and brain. We also
      highlight recent clinical findings with respect to a potential role for GDF11
      and/or myostatin in humans with heart disease. Finally, we address key
      outstanding questions related to GDF11 and myostatin dynamics and signaling
      during development, growth, and aging. 

PMID- 27034278
TI  - MicroRNAs for Restenosis and Thrombosis After Vascular Injury.
AB  - Percutaneous revascularization revolutionized the therapy of patients with
      coronary artery disease. Despite continuous technical advances that substantially
      improved patients' outcome after percutaneous revascularization, some issues are
      still open. In particular, restenosis still represents a challenge, even though
      it was dramatically reduced with the advent of drug-eluting stents. At the same
      time, drug-eluting stent thrombosis emerged as a major concern because of
      incomplete or delayed re-endothelialization after vascular injury. The discovery
      of microRNAs revealed a previously unknown layer of regulation for several
      biological processes, increasing our knowledge on the biological mechanisms
      underlying restenosis and stent thrombosis, revealing novel promising targets for
      more efficient and selective therapies. The present review summarizes recent
      experimental and clinical evidence on the role of microRNAs after arterial
      injury, focusing on practical aspects of their potential therapeutic application
      for selective inhibition of smooth muscle cell proliferation, enhancement of
      endothelial regeneration, and inhibition of platelet activation after coronary
      interventions. Application of circulating microRNAs as potential biomarkers is
      also discussed. 

PMID- 27034279
TI  - Changes in cross-sectional area of pulmonary vessels on chest computed tomography
      after chemotherapy in patients with advanced non-squamous non-small-cell lung
      cancer.
AB  - PURPOSE: Chemotherapy is associated with a risk of vascular damage. Novel anti
      angiogenic agents, which can directly affect tumor angiogenesis, are increasingly
      being used. However, the effects of these agents on normal vasculature are not
      well understood. Here, we evaluated the effects of chemotherapy in general, and
      the anti-angiogenic agent bevacizumab, more specifically, on the pulmonary
      vasculature in patients with advanced non-squamous non-small-cell lung cancer
      (NSCLC). For this, we used the cross-sectional area of pulmonary vessels (CSA),
      which is an easily measurable indicator of small pulmonary vasculature on non
      contrast chest computed tomography (CT). METHODS: We retrospectively reviewed CT
      scans of the lungs of 75 chemo-naive patients with advanced non-squamous NSCLC,
      for measurement of CSA, before and after first-line platinum-based chemotherapy,
      using a semi-automatic image-processing program. Measured vessels were classified
      in two groups: small vessels with CSA <5 mm(2) and large vessels with CSA between
      5 and 10 mm(2). The CSAs for each group of vessels were calculated and summed
      separately, and expressed as a percentage of the total lung area (%CSA<5 and
      %CSA5-10). RESULTS: Chemotherapy was associated with a selective decrease in
      small-diameter vessels, with a significant decrease in %CSA<5, but not %CSA5-10.
      When comparing chemotherapy with bevacizumab (n = 38) and without bevacizumab (n
      = 37), there was no significant difference in the reduction of %CSA<5.
      CONCLUSIONS: Platinum-based chemotherapy might induce small pulmonary vascular
      damage. Use of bevacizumab does not enhance the reduction in area of pulmonary
      vessels.

PMID- 27034277
TI  - Insulin Signaling and Heart Failure.
AB  - Heart failure is associated with generalized insulin resistance. Moreover,
      insulin-resistant states such as type 2 diabetes mellitus and obesity increases
      the risk of heart failure even after adjusting for traditional risk factors.
      Insulin resistance or type 2 diabetes mellitus alters the systemic and
      neurohumoral milieu, leading to changes in metabolism and signaling pathways in
      the heart that may contribute to myocardial dysfunction. In addition, changes in
      insulin signaling within cardiomyocytes develop in the failing heart. The changes
      range from activation of proximal insulin signaling pathways that may contribute
      to adverse left ventricular remodeling and mitochondrial dysfunction to
      repression of distal elements of insulin signaling pathways such as forkhead box
      O transcriptional signaling or glucose transport, which may also impair cardiac
      metabolism, structure, and function. This article will review the complexities of
      insulin signaling within the myocardium and ways in which these pathways are
      altered in heart failure or in conditions associated with generalized insulin
      resistance. The implications of these changes for therapeutic approaches to
      treating or preventing heart failure will be discussed. 

PMID- 27034280
TI  - Functional results after total cricoidectomy with medial femoral condyle free
      flap reconstruction.
AB  - Our goal was to describe a laryngeal-preserving single-stage procedure for the
      treatment of low-grade chondrosarcomas of the larynx: a total cricoidectomy with
      medial femoral condyle flap reconstruction. The study was designed as a case
      series of three consecutive patients with low-grade chondrosarcomas of the
      cricoid cartilage lamina, diameter 4.4, 5.2, 3.8 cm, respectively, who underwent
      total cricoidectomy in 2012. Single-staged reconstruction of the defect with
      medial femoral condyle flap including the periosteum and thin underlying cortical
      layer of the bone was conducted. Oncologic and functional results were observed
      during 3 years of follow-up. No evidence of tumor recurrence was detected during
      follow-up. One month after surgery, all patients were able to tolerate a soft
      diet and to speak satisfactorily. None of the patients reported aspiration after
      surgery nor experienced aspiration-related problems, which was confirmed by means
      of the Leipzig-Pearson scale. The speech ability was good, maximum phonation time
      was 14, 18, 21 s, respectively, and the voice handicap index scores ranged from
      24 to 36 and had improved noticeably at 1, 3 and 6 months follow-up. Two patients
      were ultimately decannulated, and one female still has a tracheostomy; however,
      she is able to keep the tracheostoma closed for most of the time, maintaining
      good phonatory and swallowing functions. Total cricoidectomy with reconstruction
      by means of medial femoral condyle flap may replace the total laryngectomy in
      large low-grade chondrosarcomas of the cricoid cartilage.

PMID- 27034281
TI  - Mean platelet volume, red cell distribution width, platelet-to-lymphocyte and
      neutrophil-to-lymphocyte ratios in patients with ankylosing spondylitis and their
      relationships with high-frequency hearing thresholds.
AB  - The mean platelet volume (MPV), red cell distribution width (RDW) and neutrophil
      to-lymphocyte ratio (NLR) comprise laboratory markers in ankylosing spondylitis
      (AS). There is a controversy in the literature regarding which type of ear
      involvement is characteristic of AS. The aim of this study was to simultaneously
      investigate the MPV, RDW, platelet to lymphocyte (PLR) and NLR in patients with
      AS and their relationships with high-frequency hearing thresholds. Thirty
      patients with AS and 35 age-matched healthy subjects were included. Each subject
      was tested with low- (250, 500, 1000 and 2000 Hz) and high- (4000, 8000, 10,000,
      12,000, 14,000 and 16,000 Hz) frequency audiometry. Additionally, the case and
      control groups were evaluated regarding the average hearing thresholds in bone
      conduction. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
      levels were measured. The RDW, MPV, neutrophils, lymphocytes and platelet counts
      were evaluated with the complete blood count. Furthermore, the NLR and PLR were
      calculated. The complete blood count, platelet numbers, ESR, CRP and NLR levels
      were significantly increased in the AS patients compared with the healthy
      controls (p < 0.001, p = 0.007, p < 0.001, p < 0.001 and p = 0.047,
      respectively). There was no statistically significant difference in the RDW, PLR
      or MPV levels (p > 0.05) in the AS patients compared with the healthy controls.
      The BASDAI score and disease duration were not correlated with the ESR, CRP
      levels, MPV, PLR, RDW or NLR in patients with AS (all; p > 0.05). The AS patients
      had increased average measurement values for the hearing threshold in both ears
      at frequencies of 250, 500, 1000 and 2000 Hz; however, there was no statistically
      significant difference (p > 0.05). The average values of the hearing threshold in
      both ears at the high frequencies of 4000, 6000, 8000, 10,000, 12,000 and 14,000
      Hz were significantly increased in the case group; however, it was not
      significantly increased at 16,000 Hz. The current study is the first to
      investigate the PLR, NLR, MPV and RDW levels in acute AS. We identified a
      significantly increased NLR, leukocyte count, ESR and CRP in AS patients.
      Sensorineural hearing loss, especially at extended high frequencies, is common in
      patients with AS and may represent an extra-articular feature of the disease. The
      combined use of NLR with the leukocyte count and other clinical assessments may
      facilitate the diagnostic process of ankylosing spondylitis.

PMID- 27034282
TI  - Introduction to the Hologenome Special Series.

PMID- 27034283
TI  - Microbes Drive Evolution of Animals and Plants: the Hologenome Concept.
AB  - The hologenome concept of evolution postulates that the holobiont (host plus
      symbionts) with its hologenome (host genome plus microbiome) is a level of
      selection in evolution. Multicellular organisms can no longer be considered
      individuals by the classical definitions of the term. Every natural animal and
      plant is a holobiont consisting of the host and diverse symbiotic microbes and
      viruses. Microbial symbionts can be transmitted from parent to offspring by a
      variety of methods, including via cytoplasmic inheritance, coprophagy, direct
      contact during and after birth, and the environment. A large number of studies
      have demonstrated that these symbionts contribute to the anatomy, physiology,
      development, innate and adaptive immunity, and behavior and finally also to
      genetic variation and to the origin and evolution of species. Acquisition of
      microbes and microbial genes is a powerful mechanism for driving the evolution of
      complexity. Evolution proceeds both via cooperation and competition, working in
      parallel. 

PMID- 27034284
TI  - Speciation by Symbiosis: the Microbiome and Behavior.
AB  - Species are fundamental units of comparison in biology. The newly discovered
      importance and ubiquity of host-associated microorganisms are now stimulating
      work on the roles that microbes can play in animal speciation. We previously
      synthesized the literature and advanced concepts of speciation by symbiosis with
      notable attention to hybrid sterility and lethality. Here, we review recent
      studies and relevant data on microbes as players in host behavior and behavioral
      isolation, emphasizing the patterns seen in these analyses and highlighting areas
      worthy of additional exploration. We conclude that the role of microbial
      symbionts in behavior and speciation is gaining exciting traction and that the
      holobiont and hologenome concepts afford an evolving intellectual framework to
      promote research and intellectual exchange between disciplines such as behavior,
      microbiology, genetics, symbiosis, and speciation. Given the increasing
      centrality of microbiology in macroscopic life, microbial symbiosis is arguably
      the most neglected aspect of animal and plant speciation, and studying it should
      yield a better understanding of the origin of species. 

PMID- 27034285
TI  - Holes in the Hologenome: Why Host-Microbe Symbioses Are Not Holobionts.
AB  - The advent of relatively inexpensive tools for characterizing microbial
      communities has led to an explosion of research exploring the diversity, ecology,
      and evolution of microbe-host systems. Some now question whether existing
      conceptual frameworks are adequate to explain microbe-host systems. One popular
      paradigm is the "holobiont-hologenome," which argues that a host and its
      microbiome evolve as a single cooperative unit of selection (i.e., a
      superorganism). We argue that the hologenome is based on overly restrictive
      assumptions which render it an approach of little research utility. A host plus
      its microbiome is more effectively viewed as an ecological community of organisms
      that encompasses a broad range of interactions (parasitic to mutualistic),
      patterns of transmission (horizontal to vertical), and levels of fidelity among
      partners. The hologenome requires high partner fidelity if it is to evolve as a
      unit. However, even when this is achieved by particular host-microbe pairs, it is
      unlikely to hold for the entire host microbiome, and therefore the community is
      unlikely to evolve as a hologenome. Both mutualistic and antagonistic (fitness
      conflict) evolution can occur among constituent members of the community, not
      just adaptations at the "hologenome" level, and there is abundant empirical
      evidence for such divergence of selective interests among members of host
      microbiome communities. We believe that the concepts and methods of ecology,
      genetics, and evolutionary biology will continue to provide a well-grounded
      intellectual framework for researching host-microbiome communities, without
      recourse to the limiting assumption that selection acts predominantly at the
      holobiont level. 

PMID- 27034287
TI  - Molecular phylogenetic analysis of Rhizobium sullae isolated from Algerian
      Hedysarum flexuosum.
AB  - Isolates from root nodules of Hedysarum flexuosum, sampled from north region of
      Algeria, were analyzed on the basis of their phenotypic and molecular
      characteristics. They were tested for their tolerance to NaCl, pH, temperatures,
      antibiotics and heavy metals resistance. Interestingly, the isolate Hf_04N
      appeared resistant to ZnCl2 (50 MUg/mL) and grew at high saline concentration up
      to 9 %. The phylogenetic positions of five isolates were studied by comparative
      sequence analysis of 16S rRNA, recA, nifH and nodD genes. There were grouped
      close to the Rhizobium sullae type strain in relation to their 16S rRNA, recA and
      nifH genes-based phylogenies. By contrast, the tree of nodD gene was not
      congruent with ribosomal, housekeeping and nitrogen fixation genes. We suggest
      that our strains have a novel nodD gene. The detection of conserved domains of
      NodD protein and nitrogenase reductase enzyme, confirm their ability to nodulate
      and fix nitrogen. 

PMID- 27034286
TI  - Altered glycosylation, expression of serum haptoglobin and alpha-1-antitrypsin in
      chronic hepatitis C, hepatitis C induced liver cirrhosis and hepatocellular
      carcinoma patients.
AB  - Liver cirrhosis with hepatitis C viral infection (HCV-LC) causes high risk to
      develop hepatocellular carcinoma (HCC). Besides diagnosis of liver cirrhosis by
      biochemical test, imaging techniques, assessment of structural liver damage by
      biopsy shows several disadvantages. Our aim was to monitor the changes in the
      expression level of serum proteins and their glycosylation pattern among chronic
      hepatitis C (HCV-CH), HCV-LC and HCC patients with respect to controls. 2D gel
      electrophoresis of HCV-CH, HCV-LC and HCC patients' sera showed several protein
      spots, which were identified by LC-MS. The change in the expression of two
      prominent protein spots, haptoglobin (Hp) and alpha 1-antitrypsin (AAT) was
      evaluated by western blot and ELISA. The changes in glycosylation pattern of
      these serum proteins were assayed using different lectins. Increased level of Hp
      and AAT was observed in HCV-LC and HCC patients' group whereas those were found
      to be present less in HCV-CH patient groups with respect to control as determined
      by ELISA using monoclonal antibodies. Decreased level of sialylation in both Hp
      and AAT was observed in HCV-LC and HCV-CH patients' group whereas increased level
      of sialylation was observed in HCC patient groups by ELISA using Sambucus nigra
      agglutinin. On the other hand increased level of fucosylation in two serum
      glycoproteins was observed in HCV-LC and HCC patients' group using Lens
      culinarris agglutinin. High glycan branching was found in HCV-LC and HCC patient
      groups in Hp but not in HCV-CH as determined by Datura stramonium agglutinin.
      However, there was no such change observed in glycan branching in AAT of HCV-CH
      and HCV-LC patients' groups, to the contrary high glycan branching was observed
      in HCC patients' group. Increased level of exposed galactose in both serum
      proteins was observed in both HCC patients' group as determined by Ricinus
      communis agglutinin. The present glycoproteomics study could predict the
      progression of HCV-CH, HCV-LC and HCC without the need of liver biopsy. 

PMID- 27034288
TI  - Frailty and sarcopenia in Bogota: results from the SABE Bogota Study.
AB  - BACKGROUND: Latin American countries like Colombia are experiencing a unique
      aging process due to a mixed epidemiological regime of communicable and non
      communicable diseases. AIMS: To estimate the prevalence of frailty and sarcopenia
      among older adults in Colombia and identify variables associated with these
      conditions. METHODS: Data come from the "Salud Bienestar y Envejecimiento" (SABE)
      Bogota Study, a cross-sectional study conducted in 2012 in Bogota, Colombia.
      Sociodemographic, health, cognitive and anthropometric measures were collected
      from 2000 community-dwelling adults aged 60 years and older. Frailty variable was
      created using the Fried phenotype and sarcopenia following the European Working
      Group on Sarcopenia in Older People algorithm. Logistic regression analyses were
      used to identify factors associated with frailty and sarcopenia. RESULTS: A total
      of 135 older adults are frail (9.4 %), while 166 have sarcopenia (11.5 %). Older
      age and female gender have a significant association with both conditions
      (Frailty: Age OR 1.05, 95 % CI 1.03-1.06, Gender OR 1.44, 95 % CI 1.12-1.84;
      Sarcopenia: Age 1.04, 95 % CI 1.02-1.07, Gender OR 1.51, 95 % CI 1.05-2.17).
      Depression was also significantly associated with frailty (OR 1.17, 95 % CI 1.12
      1.22), while smoking was significantly associated with sarcopenia (OR 2.38, 95 %
      CI 1.29-4.37). Finally, higher function, measured by independence in IADL
      (Instrumental Activities of Daily Living) was significantly associated with less
      frailty (OR 0.74, 95 % CI 0.64-0.86). Education, higher number of comorbidities,
      better MMSE score, activities of daily living disability and alcohol consumption
      were not significantly associated with frailty or sarcopenia. CONCLUSIONS:
      Frailty, sarcopenia and multimorbidity are overlapping, yet distinct conditions
      in this sample. There are potentially reversible factors that are associated with
      frailty and sarcopenia in this sample. Future studies need to analyze the best
      way to prevent these conditions, and examine individuals that have frailty,
      sarcopenia and comorbidities to design interventions to improve their quality of
      life.

PMID- 27034289
TI  - Report on January LPAI outbreak.

PMID- 27034290
TI  - Scotland sets out its strategy for animal health and welfare.

PMID- 27034291
TI  - Case of classical BSE confirmed in France.

PMID- 27034292
TI  - Countdown to compulsory microchipping.

PMID- 27034293
TI  - MP calls for review of tick treatment requirements for travelling dogs.

PMID- 27034294
TI  - FVE welcomes new guidelines on preventing tail biting in pigs.

PMID- 27034295
TI  - Veterinary medicines update.
AB  - The following information has been produced for Veterinary Record by the
      Veterinary Medicines Directorate (VMD) to provide an update for veterinary
      surgeons on recent changes to marketing authorisations for veterinary medicines
      in the UK and on other relevant issues.

PMID- 27034296
TI  - Kidney transplants in cats: RCVS considers its guidance.
AB  - ? Guidance on renal transplantation in cats ? Reforms to the governance of the
      RCVS ? Tackling non-compliance with CPD requirements. These were among matters
      discussed by the RCVS Council at its meeting on March 3. The RCVS President,
      Bradley Viner, chaired the meeting, which was held at Belgravia House, London
      SW1P.

PMID- 27034297
TI  - Disease surveillance in England and Wales, March 2016.
AB  - ? Current and emerging issue ? Highlights from the scanning surveillance network
      ? Abortion in sheep--an update ? Update on international disease threats. These
      are among matters discussed in the Animal and Plant Health Agency's (APHA's)
      March disease surveillance report.

PMID- 27034298
TI  - Breeding for good dental and oral health in rabbits.

PMID- 27034299
TI  - Selamectin versus ivermectin for cheyletiellosis in pet rabbits.
AB  - BestBETs for Vets are generated by the Centre for Evidence-based Veterinary
      Medicine at the University of Nottingham to help answer specific questions and
      assist in clinical decision making. Although evidence is often limited, they aim
      to find, present and draw conclusions from the best available evidence, using a
      standardised framework. A more detailed description of how BestBETs for Vets are
      produced was published last year (VR, April 4, 2015, pp 354-356). 

PMID- 27034300
TI  - Enrofloxacin in dairy cattle with Escherichia coli mastitis.

PMID- 27034301
TI  - Threat of imported diseases to UK dogs.

PMID- 27034302
TI  - Importance of ketamine.

PMID- 27034303
TI  - Canine osteoarthritis.

PMID- 27034312
TI  - A question of balance.
AB  - Ronnie Soutar describes his career as having been a series of accidental events
      and opportunities seized, as well as a lot of luck. 

PMID- 27034313
TI  - Diary of a parliamentary intern.
AB  - Parliamentary intern Anthony Ridge considers antimicrobial resistance and
      suspects that this year will be a major year for political decisions on this
      topic. 

PMID- 27034315
TI  - Turbulence in blood damage modeling.
AB  - PURPOSE: To account for the impact of turbulence in blood damage modeling, a
      novel approach based on the generation of instantaneous flow fields from RANS
      simulations is proposed. METHODS: Turbulent flow in a bileaflet mechanical heart
      valve was simulated using RANS-based (SST k-omega) flow solver using FLUENT 14.5.
      The calculated Reynolds shear stress (RSS) field is transformed into a set of
      divergence-free random vector fields representing turbulent velocity fluctuations
      using procedural noise functions. To consider the random path of the blood cells,
      instantaneous flow fields were computed for each time step by summation of RSS
      based divergence-free random and mean velocity fields. Using those instantaneous
      flow fields, instantaneous pathlines and corresponding point-wise instantaneous
      shear stresses were calculated. For a comparison, averaged pathlines based on
      mean velocity field and respective viscous shear stresses together with RSS
      values were calculated. Finally, the blood damage index (hemolysis) was
      integrated along the averaged and instantaneous pathlines using a power law
      approach and then compared. RESULTS: Using RSS in blood damage modeling without a
      correction factor overestimates damaging stress and thus the blood damage
      (hemolysis). Blood damage histograms based on both presented approaches differ.
      CONCLUSIONS: A novel approach to calculate blood damage without using RSS as a
      damaging parameter is established. The results of our numerical experiment
      support the hypothesis that the use of RSS as a damaging parameter should be
      avoided.

PMID- 27034314
TI  - Balance and Gait Represent Independent Domains of Mobility in Parkinson Disease.
AB  - BACKGROUND: The Instrumented Stand and Walk (ISAW) test, which includes 30
      seconds of stance, step initiation, gait, and turning, results in many objective
      balance and gait metrics from body-worn inertial sensors. However, it is not
      clear which metrics provide independent information about mobility. OBJECTIVE: It
      was hypothesized that balance and gait represent several independent domains of
      mobility and that not all domains would be abnormal in individuals with Parkinson
      disease (PD) or would change with levodopa therapy. DESIGN: This was a cross
      sectional study. METHODS: A factor analysis approach was used to identify
      independent measures of mobility extracted from the ISAW in 100 participants with
      PD and 21 control participants. First, a covariance analysis showed that postural
      sway measures were independent of gait measures. Then, the factor analysis
      revealed 6 independent factors (mobility domains: sway area, sway frequency, arm
      swing asymmetry, trunk motion during gait, gait speed, and cadence) that
      accounted for 87% of the variance of performance across participants. RESULTS:
      Sway area, gait speed, and trunk motion differed between the PD group in the off
      levodopa state and the control group, but sway frequency (but not sway area)
      differed between the PD group in the off-levodopa state and the control group.
      Four of the 6 factors changed significantly with levodopa (off to on): sway area,
      sway frequency, trunk motion during gait, and cadence. When participants were on
      levodopa, the sway area increased compared with off levodopa, becoming more
      abnormal, whereas the other 3 significant metrics moved toward, but did not
      reach, the healthy control values. LIMITATIONS: Exploratory factor analysis was
      limited to the PD population. CONCLUSIONS: The different sensitivity various
      balance and gait domains to PD and to levodopa also support neural control of at
      least 6 independent mobility domains, each of which warrants clinical assessment
      for impairments in mobility.

PMID- 27034316
TI  - In vitro evaluation of microleakage of class V cavities restored with new
      flowable compomers on the primary teeth.
AB  - INTRODUCTION: The aim of the study was to evaluate the in vitro microleakage of
      new flowable compomers in the class V cavities of primary teeth. METHODS: Thirty
      freshly extracted, non-carious, primary molars without visible defects were used
      in this study. Class V cavities (n = 60), with the occlusal and cervical margins
      located in the enamel, were prepared on the buccal and lingual surfaces. The
      samples were randomly divided into 3 groups of 20 each. Group 1: restored with
      Twinky Star Flow (Voco, Cuxhaven, Germany), Group 2: restored with Dyract Flow
      (Dentsply, Konstanz, Germany) and Group 3: restored with R&D Series Nova Compomer
      Flow (Imicryl, Konya, Turkey) according to the manufacturer's instructions. After
      a thermocycling regimen of 1000 cycles between 5 degrees C and 55 degrees C, the
      samples were isolated, immersed in 0.5% basic fuchsine solution for 24 h at 37
      degrees C and sectioned longitudinally in a buccolingual direction. The sections
      were evaluated for values of microleakage with a stereomicroscope. RESULTS: All
      materials showed microleakage but no statistically significant difference was
      observed among the groups (p>0.05). The highest microleakage score was observed
      in group II (1.65 +/- 0.49) and group I (1.75 +/- 0.44) at occlusal and gingival
      margins, respectively. CONCLUSIONS: Flowable compomers showed insignificantly
      least amount of microleakage in class V cavities prepared on primary molars.

PMID- 27034317
TI  - Apically extruded debris during root canal preparation using ProTaper Gold,
      ProTaper Universal, ProTaper Next, and RECIPROC instruments.
AB  - PURPOSE: The aim of this study was to determine the amount of apically extruded
      debris during root canal preparation with ProTaper Gold (PTG) (Dentsply
      Maillefer, Ballaigues, Switzerland), ProTaper Universal (PTU) (Dentsply
      Maillefer), ProTaper Next (PTN) (Dentsply Maillefer), and RECIPROC (VDW, Munich,
      Germany) in curved canals. METHODS: Eighty human mandibular molar teeth were
      divided into 4 groups according to the system used for root canal preparation:
      PTG, PTU, PTN, and RECIPROC groups. The mean weight of extruded debris was
      statistically analyzed using one-way analysis of variance and post-hoc Tukey's
      test (alpha = 0.05). RESULTS: The PTU was associated with significantly more
      extruded debris than the PTG, PTN, and RECIPROC (p<0.05). The PTG was associated
      with significantly more extruded debris than the PTN and RECIPROC (p<0.05),
      whereas no significant difference was found between the RECIPROC and PTN
      (p>0.05). CONCLUSIONS: All systems caused apical debris extrusion during curved
      canal preparations. However, the PTG, PTN, and RECIPROC systems resulted in
      significantly less debris extrusion than the PTU system.

PMID- 27034318
TI  - Microfluidic approaches for the assessment of blood cell trauma: a focus on
      thrombotic risk in mechanical circulatory support devices.
AB  - INTRODUCTION: Mechanical circulatory support devices (MCSDs) are emerging as a
      valuable therapeutic option for the management of end-stage heart failure.
      However, although recipients are routinely administered with anti-thrombotic (AT)
      drugs, thrombosis persists as a severe post-implant complication. Conventional
      clinical assays and coagulation markers demonstrate partial ability in preventing
      the onset of thrombosis. Through years, different laboratory techniques have been
      proposed as potential tools for the evaluation of platelets' hemostatic response
      in MCSD recipients. Most rely on platelet aggregation tests; they are performed
      in static or low shear conditions, neglecting the prominent contribution of MCSD
      shear-induced mechanical load in enhancing platelet activation (PA). On the other
      hand, those tests able to account for shear-induced PA have limited possibility
      of effective clinical translation. AIMS AND METHODS: Advances on this side have
      been addressed by microfluidic technology. Microfluidic devices have been
      developed for AT drug monitoring under flow, able to replicate physiological
      and/or constant shear flow conditions in vitro. In this paper, we present a newly
      developed microfluidic platform able to expose platelets to MCSD-specific dynamic
      shear stress patterns. We performed in vitro tests circulating human platelets in
      the microfluidic platform and quantifying the dynamics of PA by means of the
      Platelet Activity State (PAS) assay. RESULTS: Our results prove the feasibility
      of using microfluidics for the diagnosis of MCSD-related thrombotic risk. This
      study paves the way for the development of a miniaturized point-of-care device
      for monitoring AT drug regimen. Such a system may have significant impact on
      limiting the incidence of thrombosis in MCSD recipients.

PMID- 27034319
TI  - A two-stage rotary blood pump design with potentially lower blood trauma: a
      computational study.
AB  - AIM: In current rotary blood pumps, complications related to blood trauma due to
      shear stresses are still frequently observed clinically. Reducing the rotor tip
      speed might decrease blood trauma. Therefore, the aim of this project was to
      design a two-stage rotary blood pump leading to lower shear stresses. METHODS:
      Using the principles of centrifugal pumps, two diagonal rotor stages were
      designed with an outer diameter of 22 mm. The first stage begins with a flow
      straightener and terminates with a diffusor, while a volute casing behind the
      second stage is utilized to guide fluid to the outlet. Both stages are combined
      into one rotating part which is pivoted by cup-socket ruby bearings. Details of
      the flow field were analyzed employing computational fluid dynamics (CFD). A
      functional model of the pump was fabricated and the pressure-flow dependency was
      experimentally assessed. RESULTS: Measured pressure-flow performance of the
      developed pump indicated its ability to generate adequate pressure heads and
      flows with characteristic curves similar to centrifugal pumps. According to the
      CFD results, a pressure of 70 mmHg was produced at a flow rate of 5 L/min and a
      rotational speed of 3200 rpm. Circumferential velocities could be reduced to 3.7
      m/s as compared to 6.2 m/s in a clinically used axial rotary blood pump. Flow
      fields were smooth with well-distributed pressure fields and comparatively few
      recirculation or vortices. Substantially smaller volumes were exposed to high
      shear stresses >150 Pa. CONCLUSIONS: Hence, blood trauma might be reduced with
      this design. Based on these encouraging results, future in vitro investigations
      to investigate actual blood damage are intended.

PMID- 27034321
TI  - A new approach for semiempirical modeling of mechanical blood trauma.
AB  - PURPOSE: Two semi-empirical models were recently published, both making use of
      existing literature data, but each taking into account different physical
      phenomena that trigger hemolysis. In the first model, hemoglobin (Hb) release is
      described as a permeation procedure across the membrane, assuming a shear stress
      dependent process (sublethal model). The second model only accounts for
      hemoglobin release that is caused by cell membrane breakdown, which occurs when
      red blood cells (RBC) undergo mechanically induced shearing for a period longer
      than the threshold time (nonuniform threshold model). In this paper, we introduce
      a model that considers the hemolysis generated by both these possible phenomena.
      METHODS: Since hemolysis can possibly be caused by permeation of hemoglobin
      through the RBC functional membrane as well as by release of hemoglobin from RBC
      membrane breakdown, our proposed model combines both these models. An
      experimental setup consisting of a Couette device was utilized for validation of
      our proposed model. RESULTS: A comparison is presented between the damage index
      (DI) predicted by the proposed model vs. the sublethal model vs. the nonthreshold
      model and experimental datasets. This comparison covers a wide range of shear
      stress for both human and porcine blood. An appropriate agreement between the
      measured DI and the DI predicted by the present model was obtained. CONCLUSIONS:
      The semiempirical hemolysis model introduced in this paper aims for significantly
      enhanced conformity with experimental data. Two phenomenological outcomes become
      possible with the proposed approach: an estimation of the average time after
      which cell membrane breakdown occurs under the applied conditions, and a
      prediction of the ratio between the phenomena involved in hemolysis.

PMID- 27034322
TI  - Junior doctors' contract and equality analysis are published.

PMID- 27034320
TI  - Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding
      hemolysis.
AB  - After many decades of improvements in mechanical circulatory assist devices
      (CADs), blood damage remains a serious problem during support contributing to
      variety of adverse events, and consequently affecting patient survival and
      quality of life. The mechanisms of cumulative cell damage in continuous-flow
      blood pumps are still not fully understood despite numerous in vitro, in vivo,
      and in silico studies of blood trauma. Previous investigations have almost
      exclusively focused on lethal blood damage, namely hemolysis, which is typically
      negligible during normal operation of current generation CADs. The measurement of
      plasma free hemoglobin (plfHb) concentration to characterize hemolysis is
      straightforward, however sublethal trauma is more difficult to detect and
      quantify since no simple direct test exists. Similarly, while multiple studies
      have focused on thrombosis within blood pumps and accessories, sublethal blood
      trauma and its sequelae have yet to be adequately documented or characterized.
      This review summarizes the current understanding of sublethal trauma to red blood
      cells (RBCs) produced by exposure of blood to flow parameters and conditions
      similar to those within CADs. It also suggests potential strategies to reduce
      and/or prevent RBC sublethal damage in a clinically-relevant context, and
      encourages new research into this relatively uncharted territory. 

PMID- 27034323
TI  - Cerebral oxygenation and echocardiographic parameters in preterm neonates with a
      patent ductus arteriosus: an observational study.
AB  - BACKGROUND: A haemodynamically significant patent ductus arteriosus (hsPDA) is
      clinically suspected and confirmed by echocardiographic examination. A hsPDA
      decreases cerebral blood flow and oxygen saturation by the ductal steal
      phenomenon. AIM: To determine the relationship between echocardiographic
      parameters, cerebral oxygenation and a hsPDA in preterm infants. METHODS: 380
      preterm infants (<32 weeks gestational age) born between 2008 and 2010 were
      included. Blinded echocardiographic examination was performed on the second,
      fourth and sixth day after birth. Examinations were deblinded when hsPDA was
      clinically suspected. Regional cerebral oxygen saturation (rScO2) was
      continuously monitored by near-infrared spectroscopy during 72 h after birth, and
      afterwards for at least 1 h before echocardiography. Echocardiographic parameters
      included ductal diameter, end-diastolic flow in the left pulmonary artery, left
      atrium/aorta ratio and ductal flow pattern. RESULTS: rScO2 was significantly
      related only to ductal diameter over time. Mixed modelling analysed the course of
      rScO2 over time, where infants were divided into four groups: a closed duct, an
      open haemodynamically insignificant duct (non-sPDA), a hsPDA, which was
      successfully closed during study period (SC hsPDA) or a hsPDA, which was
      unsuccessfully closed during study period (UC hsPDA). SC hsPDA infants showed the
      highest rScO2 on day 6, while UC hsPDA infants had the lowest rScO2 values.
      CONCLUSIONS: Ductal diameter is the only echocardiographic parameter
      significantly related to cerebral oxygenation over time. Cerebral oxygenation
      takes a different course over time depending on the status of the duct. Low
      cerebral oxygenation may be suggestive of a hsPDA.

PMID- 27034324
TI  - Human Trafficking in Ethiopia: A Scoping Review to Identify Gaps in Service
      Delivery, Research, and Policy.
AB  - The purpose of this review is to integrate evidence on human trafficking in
      Ethiopia and identify gaps and recommendations for service delivery, research and
      training, and policy. A scoping literature review approach was used to
      systematically search nursing, medical, psychological, law, and international
      databases and synthesize information on a complex, understudied topic. The search
      yielded 826 articles, and 39 met the predetermined criteria for inclusion in the
      review. Trafficking in Ethiopia has occurred internally and externally in the
      form of adult and child labor and sex trafficking. There were also some reports
      of organ trafficking and other closely related human rights violations, such as
      child marriage, child soldiering, and exploitative intercountry adoption. Risk
      factors for trafficking included push factors (poverty, political instability,
      economic problems, and gender discrimination) and pull factors (demand for cheap
      labor). Trafficking was associated with poor health and economic outcomes for
      victims. Key recommendations for service delivery, research and training, and
      policy are identified, including establishing comprehensive services for survivor
      rehabilitation and reintegration, conducting quantitative health outcomes
      research, and reforming policy around migration and trafficking. Implementing the
      recommendations identified by this review will allow policy makers, researchers,
      and practitioners to take meaningful steps toward confronting human trafficking
      in Ethiopia.

PMID- 27034325
TI  - Sexual Assault and Justice for Older Women: A Critical Review of the Literature.
AB  - This article provides a critical review of current literature on the sexual
      assault of older women-including an exploration of the specific features and
      emotional and physical impacts of older women's experiences-and highlights
      current gaps and future directions for research, practice, and theory. A review
      of the literature indicates that older women constitute only a small proportion
      of victim/survivors. However, there is evidence to suggest that existing research
      underestimates the extent of this issue. Older women face particular barriers to
      disclosure and accessing the justice system, resulting in their experiences
      remaining hidden. Many of these barriers also contribute toward older women's
      experiences being ignored, dismissed, or downplayed by potential bystanders.
      These barriers are explored in depth in this article and include cultural
      context, ageism, cognitive and health impairments, and living in a residential
      care setting. Responding to, and preventing, the sexual assault of older women
      requires a tailored approach-and we currently lack sufficient insight to develop
      appropriate responses. In closing, this article considers how we might work
      toward achieving "justice" for older women victim/survivors.

PMID- 27034326
TI  - Detecting QTLs and putative candidate genes involved in budbreak and flowering
      time in an apple multiparental population.
AB  - In temperate trees, growth resumption in spring time results from chilling and
      heat requirements, and is an adaptive trait under global warming. Here, the
      genetic determinism of budbreak and flowering time was deciphered using five
      related full-sib apple families. Both traits were observed over 3 years and two
      sites and expressed in calendar and degree-days. Best linear unbiased predictors
      of genotypic effect or interaction with climatic year were extracted from mixed
      linear models and used for quantitative trait locus (QTL) mapping, performed with
      an integrated genetic map containing 6849 single nucleotide polymorphisms (SNPs),
      grouped into haplotypes, and with a Bayesian pedigree-based analysis. Four major
      regions, on linkage group (LG) 7, LG10, LG12, and LG9, the latter being the most
      stable across families, sites, and years, explained 5.6-21.3% of trait variance.
      Co-localizations for traits in calendar days or growing degree hours (GDH)
      suggested common genetic determinism for chilling and heating requirements.
      Homologs of two major flowering genes, AGL24 and FT, were predicted close to LG9
      and LG12 QTLs, respectively, whereas Dormancy Associated MADs-box (DAM) genes
      were near additional QTLs on LG8 and LG15. This suggests that chilling perception
      mechanisms could be common among perennial and annual plants. Progenitors with
      favorable alleles depending on trait and LG were identified and could benefit new
      breeding strategies for apple adaptation to temperature increase.

PMID- 27034327
TI  - Dominant and recessive mutations in the Raf-like kinase HT1 gene completely
      disrupt stomatal responses to CO2 in Arabidopsis.
AB  - HT1 (HIGH LEAF TEMPERATURE 1) is the first component associated with changes in
      stomatal aperture in response to CO2 to be isolated by forward genetic screening.
      The HT1 gene encodes a protein kinase expressed mainly in guard cells. The loss
      of-function ht1-1 and ht1-2 mutants in Arabidopsis thaliana have CO2
      hypersensitive stomatal closure with concomitant reductions in their kinase
      activities in vitro In addition to these mutants, in this study we isolate or
      obtaine five new ht1 alleles (ht1-3, ht1-4, ht1-5, ht1-6, and ht1-7). Among the
      mutants, only ht1-3 has a dominant mutant phenotype and has widely opened stomata
      due to CO2 insensitivity. The ht1-3 mutant has a missense mutation affecting a
      non-conserved residue (R102K), whereas the other six recessive mutants have
      mutations in highly conserved residues in the catalytic domains required for
      kinase activity. We found that the dominant mutation does not affect the
      expression of HT1 or the ability to phosphorylate casein, a universal kinase
      substrate, but it does affect autophosphorylation activity in vitro A 3D
      structural model of HT1 also shows that the R102 residue protrudes from the
      surface of the kinase, implying a role for the formation of oligomers and/or
      interaction with its targets. We demonstrate that both the loss-of-function and
      gain-of-function ht1 mutants have completely disrupted CO2 responses, although
      they have normal responses to ABA. Furthermore, light-induced stomatal opening is
      smaller in ht1-3 and much smaller in ht1-2 Taken together, these results indicate
      that HT1 is a critical regulator for CO2 signaling and is partially involved in
      the light-induced stomatal opening pathway.

PMID- 27034328
TI  - Up-regulating the abscisic acid inactivation gene ZmABA8ox1b contributes to seed
      germination heterosis by promoting cell expansion.
AB  - Heterosis has been widely used in agriculture, but the underlying molecular
      principles are still largely unknown. During seed germination, we observed that
      maize (Zea mays) hybrid B73/Mo17 was less sensitive than its parental inbred
      lines to exogenous abscisic acid (ABA), and endogenous ABA content in hybrid
      embryos decreased more rapidly than in the parental inbred lines. ZmABA8ox1b, an
      ABA inactivation gene, was consistently more highly up-regulated in hybrid
      B73/Mo17 than in its parental inbred lines at early stages of seed germination.
      Moreover, ectopic expression of ZmABA8ox1b obviously promoted seed germination in
      Arabidopsis Remarkably, microscopic observation revealed that cell expansion
      played a major role in the ABA-mediated maize seed germination heterosis, which
      could be attributed to the altered expression of cell wall-related genes.

PMID- 27034330
TI  - Do We Care? Should We?

PMID- 27034331
TI  - Confounding by Indication: Letter to the Editor.

PMID- 27034329
TI  - OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T
      Cell Responses and Associate with Metastatic Potential.
AB  - PURPOSE: Cutaneous squamous cell carcinoma (cSCC) is the most common human cancer
      with metastatic potential. Despite T cells accumulating around cSCCs, these
      tumors continue to grow and persist. To investigate reasons for failure of T
      cells to mount a protective response in cSCC, we focused on regulatory T cells
      (Tregs) as this suppressive population is well represented among the infiltrating
      lymphocytes. EXPERIMENTAL DESIGN: Flow cytometry was conducted on cSCC
      lymphocytes and in vitro functional assays were performed using sorted tumoral T
      cells. Lymphocyte subsets in primary cSCCs were quantified immunohistochemically.
      RESULTS: FOXP3(+) Tregs were more frequent in cSCCs than in peripheral blood (P <
      0.0001, n = 86 tumors). Tumoral Tregs suppressed proliferation of tumoral
      effector CD4(+) (P = 0.005, n = 10 tumors) and CD8(+) T cells (P = 0.043, n = 9
      tumors) and inhibited IFNgamma secretion by tumoral effector T cells (P = 0.0186,
      n = 11 tumors). The costimulatory molecule OX40 was expressed predominantly on
      tumoral Tregs (P < 0.0001, n = 15 tumors) and triggering OX40 with an agonist
      anti-OX40 antibody overcame the suppression exerted by Tregs, leading to
      increased tumoral effector CD4(+) lymphocyte proliferation (P = 0.0098, n = 10
      tumors). Tregs and OX40(+) lymphocytes were more abundant in primary cSCCs that
      metastasized than in primary cSCCs that had not metastasized (n = 48 and n = 49
      tumors, respectively). CONCLUSIONS: Tregs in cSCCs suppress effector T-cell
      responses and are associated with subsequent metastasis, suggesting a key role
      for Tregs in cSCC development and progression. OX40 agonism reversed the
      suppressive effects of Tregs in vitro, suggesting that targeting OX40 could
      benefit the subset of cSCC patients at high risk of metastasis. Clin Cancer Res;
      22(16); 4236-48. (c)2016 AACR.

PMID- 27034332
TI  - Confounding by Indication: Response.

PMID- 27034333
TI  - The Role of the Anterolateral Structures and the ACL in Controlling Laxity of the
      Intact and ACL-Deficient Knee: Letter to the Editor.

PMID- 27034334
TI  - The Role of the Anterolateral Structures and the ACL in Controlling Laxity of the
      Intact and ACL-Deficient Knee: Response.

PMID- 27034335
TI  - Is Subchondral Acetabular Edema or Cystic Change on MRI a Contraindication for
      Hip Arthroscopy in Patients With FAI? Letter to the Editor.

PMID- 27034336
TI  - Is Subchondral Acetabular Edema or Cystic Change on MRI a Contraindication for
      Hip Arthroscopy in Patients With FAI? Response.

PMID- 27034337
TI  - Considering chance in quality and safety performance measures: an analysis of
      performance reports by boards in English NHS trusts.
AB  - OBJECTIVES: Hospital board members are asked to consider large amounts of quality
      and safety data with a duty to act on signals of poor performance. However, in
      order to do so it is necessary to distinguish signals from noise (chance). This
      article investigates whether data in English National Health Service (NHS) acute
      care hospital board papers are presented in a way that helps board members
      consider the role of chance in their decisions. METHODS: Thirty English NHS
      trusts were selected at random and their board papers retrieved. Charts depicting
      quality and safety were identified. Categorical discriminations were then
      performed to document the methods used to present quality and safety data in
      board papers, with particular attention given to whether and how the charts
      depicted the role of chance, that is, by including control lines or error bars.
      RESULTS: Thirty board papers, containing a total of 1488 charts, were sampled.
      Only 88 (6%) of these charts depicted the role of chance, and only 17 of the 30
      board papers included any charts depicting the role of chance. Of the 88 charts
      that attempted to represent the role of chance, 16 included error bars and 72
      included control lines. Only 6 (8%) of the 72 control charts indicated where the
      control lines had been set (eg, 2 vs 3 SDs). CONCLUSIONS: Hospital board members
      are expected to consider large amounts of information. Control charts can help
      board members distinguish signals from noise, but often boards are not using
      them. We discuss demand-side and supply-side barriers that could be overcome to
      increase use of control charts in healthcare.

PMID- 27034338
TI  - From stoplight reports to time series: equipping boards and leadership teams to
      drive better decisions.

PMID- 27034339
TI  - The problem with red, amber, green: the need to avoid distraction by random
      variation in organisational performance measures.

PMID- 27034340
TI  - Retrospective study of reticulocyte indices as indicators of iron-restricted
      erythropoiesis in dogs with immune-mediated hemolytic anemia.
AB  - Iron-restricted erythropoiesis can occur as a result of an absolute deficiency of
      iron stores, inflammation-mediated iron sequestration, or functional iron
      deficiency (in which release of stored iron is slower than the iron uptake by
      erythroid precursors during intense erythropoiesis). Reticulocyte indices are
      used to identify iron-restricted erythropoiesis, with the reticulocyte hemoglobin
      content (CHr) being the most commonly used index in human patients. Dogs with
      immune-mediated hemolytic anemia (IMHA) may have iron-restricted erythropoiesis
      caused by inflammation-mediated iron sequestration and/or functional iron
      deficiency, which could contribute to anemia severity and blunt the regenerative
      response in some dogs. To investigate this possibility, reticulocyte indices were
      examined retrospectively in 14 dogs (2-15 years of age; 9 spayed females, 1
      intact female, 4 neutered males) with IMHA, and no clinical evidence of blood
      loss was found to suggest absolute iron deficiency. Five dogs (34%) had CHr below
      the preestablished lower reference limit (24.5 pg), and hematocrit was
      significantly lower in these dogs (p = 0.042, nonpaired t-test). Our results
      suggest that some dogs with IMHA may have iron-restricted erythropoiesis as a
      result of functional iron deficiency, inflammation-mediated iron sequestration,
      or (less likely) absolute iron deficiency. Further study is warranted to evaluate
      if dogs with IMHA may benefit from parenteral iron therapy. 

PMID- 27034341
TI  - Pathology of ear hematomas in swine.
AB  - The objectives of our study were to describe the pathology of ear hematomas in
      swine and to add to the comprehension of the pathogenesis of this condition. The
      pathogenesis of aural hematomas has been studied mainly in dogs; however,
      disagreements exist about the precise anatomic location of the hemorrhage.
      Sixteen pigs with ear hematoma at various stages of development were included in
      this study. The pigs were submitted for routine autopsy for various and unrelated
      reasons over a period of several years. Based on gross examination, the 16 cases
      of aural hematomas were subjectively classified as acute (n = 6), subacute (n =
      3), and chronic (n = 7). The age of the animals at the time of autopsy ranged
      from 2 weeks to adulthood, with all acute cases being <7 weeks of age.
      Morphologic examination of all acute cases revealed that the hematoma developed
      predominantly in a subperichondral location on both sides of the cartilaginous
      plate simultaneously. Within these same cases, there were also some areas in
      which blood-filled clefts had formed within the cartilage itself. Besides
      fibroplasia, neoformation of cartilage was found to represent a significant part
      of the repair process. All chronic cases were characterized on cross-section of
      the ear by the presence of at least 2 distinct, wavy, focally folded, and roughly
      parallel plates of cartilage separated from each other by fibrous tissue. 

PMID- 27034342
TI  - Development of a consensus reverse transcription PCR assay for the specific
      detection of tortoise picornaviruses.
AB  - Picornaviruses (PVs) of different terrestrial tortoise species, previously
      designated as Virus "X," have been frequently detected from various tissues by
      virus isolation in Terrapene heart cell culture as the preferred laboratory
      method for diagnosis. Here, we describe the development of 2 diagnostic reverse
      transcription (RT)-PCR-based assays for the identification and characterization
      of tortoise PVs belonging to the tentative genus Topivirus To test the novel
      diagnostic systems, PVs were isolated from swab and tissue samples collected in
      Germany, Italy, and Hungary between 2000 and 2013. All 25 tested isolates gave
      positive results with both novel consensus primer sets. Sequencing of the
      amplified products confirmed that all studied viruses were members of the new
      proposed genus Topivirus Phylogenetic analyses clearly distinguished 2 lineages
      within the genus. Based on sequence analysis, no association was observed between
      the geographic distribution and genetic relatedness. Furthermore, no strict host
      specificity was indicated. The PCR-based diagnosis may provide a time-saving and
      sensitive method to detect tortoise PVs, and evaluation of PV presence in these
      animals may help control virus spread. 

PMID- 27034344
TI  - Formyl Peptide Receptor 2 Plays a Deleterious Role During Influenza A Virus
      Infections.
AB  - BACKGROUND: The pathogenesis of influenza A virus (IAV) infections is a
      multifactorial process that includes the replication capacity of the virus and a
      harmful inflammatory response to infection. Formyl peptide receptor 2 (FPR2)
      emerges as a central receptor in inflammatory processes controlling resolution of
      acute inflammation. Its role in virus pathogenesis has not been investigated yet.
      METHODS: We used pharmacologic approaches to investigate the role of FPR2 during
      IAV infection in vitro and in vivo. RESULTS: In vitro, FPR2 expressed on A549
      cells was activated by IAV, which harbors its ligand, annexin A1, in its
      envelope. FPR2 activation by IAV promoted viral replication through an
      extracellular-regulated kinase (ERK)-dependent pathway. In vivo, activating FPR2
      by administering the agonist WKYMVm-NH2 decreased survival and increased viral
      replication and inflammation after IAV infection. This effect was abolished by
      treating the mice with U0126, a specific ERK pathway inhibitor, showing that, in
      vivo, the deleterious role of FPR2 also occurs through an ERK-dependent pathway.
      In contrast, administration of the FPR2 antagonist WRW4 protected mice from
      lethal IAV infections. CONCLUSIONS: These data show that viral replication and
      IAV pathogenesis depend on FPR2 signaling and suggest that FPR2 may be a
      promising novel strategy to treat influenza.

PMID- 27034343
TI  - Autoimmune Variant PTPN22 C1858T Is Associated With Impaired Responses to
      Influenza Vaccination.
AB  - High-affinity-antibody production, T-cell activation, and interferon upregulation
      all contribute to protective immunity that occurs in humans following influenza
      immunization. Hematopoietic cell-specific PTPN22 encodes lymphoid phosphatase
      (Lyp), which regulates lymphocyte antigen receptor and pattern recognition
      receptor (PRR) signaling. A PTPN22 variant, R620W (LypW), predisposes to
      autoimmune and infectious diseases and confers altered signaling through antigen
      receptors and PRRs. We tested the hypothesis that LypW-bearing humans would have
      diminished immune response to trivalent influenza vaccine (TIV). LypW carriers
      exhibited decreased induction of influenza virus-specific CD4(+) T cells
      expressing effector cytokines and failed to increase antibody affinity following
      TIV receipt. No differences between LypW carriers and noncarriers were observed
      in virus-specific CD8(+) T-cell responses, early interferon transcriptional
      responses, or myeloid antigen-presenting cell costimulatory molecule
      upregulation. The association of LypW with defects in TIV-induced CD4(+) T-cell
      expansion and antibody affinity maturation suggests that LypW may predispose
      individuals to have a diminished capacity to generate protective immunity against
      influenza virus.

PMID- 27034346
TI  - New frontiers in bioscience.

PMID- 27034348
TI  - ECOLOGY. El Nino's warmth devastating reefs worldwide.

PMID- 27034349
TI  - PLANETARY SCIENCE. Sandy ripples point to Mars's past.

PMID- 27034345
TI  - Identifying Key Drivers of the Impact of an HIV Cure Intervention in Sub-Saharan
      Africa.
AB  - BACKGROUND: It is unknown what properties would be required to make an
      intervention in low income countries that can eradicate or control human
      immunodeficiency virus (HIV) without antiretroviral therapy (ART) cost-effective.
      METHODS: We used a model of HIV and ART to investigate the effect of introducing
      an ART-free viral suppression intervention in 2022 using Zimbabwe as an example
      country. We assumed that the intervention (cost: $500) would be accessible for
      90% of the population, be given to those receiving effective ART, have sufficient
      efficacy to allow ART interruption in 95%, with a rate of viral rebound of 5% per
      year in the first 3 months, and a 50% decline in rate with each successive year.
      RESULTS: An ART-free viral suppression intervention with these properties would
      result in >0.53 million disability-adjusted-life-years averted over 2022-2042,
      with a reduction in HIV program costs of $300 million (8.7% saving). An
      intervention of this efficacy costing anything up to $1400 is likely to be cost
      effective in this setting. CONCLUSIONS: Interventions aimed at curing HIV
      infection have the potential to improve overall disease burden and to reduce
      costs. Given the effectiveness and cost of ART, such interventions would have to
      be inexpensive and highly effective.

PMID- 27034351
TI  - SCIENCE FUNDING. Canadian scientists smile at Liberals' deja vu budget.

PMID- 27034350
TI  - CANCER RESEARCH. Brazil bill would legalize renegade cancer pill.

PMID- 27034352
TI  - BIOMEDICINE. No-strings awards at NIH draw concern.

PMID- 27034353
TI  - Immunity goes local.

PMID- 27034354
TI  - Occupational hazard.

PMID- 27034357
TI  - MITOCHONDRIA. Mitochondrial disease therapy from thin air?

PMID- 27034358
TI  - ORGANIC CHEMISTRY. Rethinking the S(N)2 reaction.

PMID- 27034359
TI  - DEVELOPMENT. Nursing the oocyte.

PMID- 27034360
TI  - ASTRONOMY. An odd one out.

PMID- 27034361
TI  - SOCIAL SCIENCE AND SUSTAINABILITY. Engage key social concepts for sustainability.

PMID- 27034362
TI  - SELF-ASSEMBLY. Colloidal crystal ordering in a liquid crystal.

PMID- 27034363
TI  - BEHAVIOR. A brain conditioned for social defeat.

PMID- 27034364
TI  - RNA. A lncRNA links genomic variation with celiac disease.

PMID- 27034365
TI  - CHEMICAL SYNTHESIS. Going with the flow.

PMID- 27034366
TI  - On-demand continuous-flow production of pharmaceuticals in a compact,
      reconfigurable system.
AB  - Pharmaceutical manufacturing typically uses batch processing at multiple
      locations. Disadvantages of this approach include long production times and the
      potential for supply chain disruptions. As a preliminary demonstration of an
      alternative approach, we report here the continuous-flow synthesis and
      formulation of active pharmaceutical ingredients in a compact, reconfigurable
      manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized
      [1.0 meter (width) * 0.7 meter (length) * 1.8 meter (height)] system produces
      sufficient quantities per day to supply hundreds to thousands of oral or topical
      liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam,
      and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying
      this flexible plug-and-play approach are substantial enabling advances in
      continuous-flow synthesis, complex multistep sequence telescoping, reaction
      engineering equipment, and real-time formulation. 

PMID- 27034367
TI  - A white dwarf with an oxygen atmosphere.
AB  - Stars born with masses below around 10 solar masses end their lives as white
      dwarf stars. Their atmospheres are dominated by the lightest elements because
      gravitational diffusion brings the lightest element to the surface. We report the
      discovery of a white dwarf with an atmosphere completely dominated by oxygen,
      SDSS J124043.01+671034.68. After oxygen, the next most abundant elements in its
      atmosphere are neon and magnesium, but these are lower by a factor of >=25 by
      number. The fact that no hydrogen or helium are observed is surprising. Oxygen,
      neon, and magnesium are the products of carbon burning, which occurs in stars at
      the high-mass end of pre-white dwarf formation. This star, a possible oxygen-neon
      white dwarf, will provide a rare observational test of the evolutionary paths
      toward white dwarfs. 

PMID- 27034368
TI  - Triclinic nematic colloidal crystals from competing elastic and electrostatic
      interactions.
AB  - The self-assembly of nanoparticles can enable the generation of composites with
      predesigned properties, but reproducing the structural diversity of atomic and
      molecular crystals remains a challenge. We combined anisotropic elastic and
      weakly screened electrostatic interactions to guide both orientational and
      triclinic positional self-ordering of inorganic nanocrystals in a nematic fluid
      host. The lattice periodicity of these low-symmetry colloidal crystals is more
      than an order of magnitude larger than the nanoparticle size. The orientations of
      the nanocrystals, as well as the crystallographic axes of the ensuing triclinic
      colloidal crystals, are coupled to the uniform alignment direction of the nematic
      host, which can be readily controlled on large scales. We examine colloidal pair
      and many-body interactions and show how triclinic crystals with orientational
      ordering of the semiconductor nanorods emerge from competing long-range elastic
      and electrostatic forces. 

PMID- 27034369
TI  - Tuning the activity of Pt alloy electrocatalysts by means of the lanthanide
      contraction.
AB  - The high platinum loadings required to compensate for the slow kinetics of the
      oxygen reduction reaction (ORR) impede the widespread uptake of low-temperature
      fuel cells in automotive vehicles. We have studied the ORR on eight platinum (Pt)
      lanthanide and Pt-alkaline earth electrodes, Pt5M, where M is lanthanum, cerium,
      samarium, gadolinium, terbium, dysprosium, thulium, or calcium. The materials are
      among the most active polycrystalline Pt-based catalysts reported, presenting
      activity enhancement by a factor of 3 to 6 over Pt. The active phase consists of
      a Pt overlayer formed by acid leaching. The ORR activity versus the bulk lattice
      parameter follows a high peaked "volcano" relation. We demonstrate how the
      lanthanide contraction can be used to control strain effects and tune the
      activity, stability, and reactivity of these materials. 

PMID- 27034370
TI  - Antarctic Ice Sheet variability across the Eocene-Oligocene boundary climate
      transition.
AB  - About 34 million years ago, Earth's climate cooled and an ice sheet formed on
      Antarctica as atmospheric carbon dioxide (CO2) fell below ~750 parts per million
      (ppm). Sedimentary cycles from a drill core in the western Ross Sea provide
      direct evidence of orbitally controlled glacial cycles between 34 million and 31
      million years ago. Initially, under atmospheric CO2 levels of >=600 ppm, a
      smaller Antarctic Ice Sheet (AIS), restricted to the terrestrial continent, was
      highly responsive to local insolation forcing. A more stable, continental-scale
      ice sheet calving at the coastline did not form until ~32.8 million years ago,
      coincident with the earliest time that atmospheric CO2 levels fell below ~600
      ppm. Our results provide insight into the potential of the AIS for threshold
      behavior and have implications for its sensitivity to atmospheric CO2
      concentrations above present-day levels.

PMID- 27034371
TI  - Consistent response of bird populations to climate change on two continents.
AB  - Global climate change is a major threat to biodiversity. Large-scale analyses
      have generally focused on the impacts of climate change on the geographic ranges
      of species and on phenology, the timing of ecological phenomena. We used long
      term monitoring of the abundance of breeding birds across Europe and the United
      States to produce, for both regions, composite population indices for two groups
      of species: those for which climate suitability has been either improving or
      declining since 1980. The ratio of these composite indices, the climate impact
      indicator (CII), reflects the divergent fates of species favored or disadvantaged
      by climate change. The trend in CII is positive and similar in the two regions.
      On both continents, interspecific and spatial variation in population abundance
      trends are well predicted by climate suitability trends. 

PMID- 27034372
TI  - Social conflict resolution regulated by two dorsal habenular subregions in
      zebrafish.
AB  - When animals encounter conflict they initiate and escalate aggression to
      establish and maintain a social hierarchy. The neural mechanisms by which animals
      resolve fighting behaviors to determine such social hierarchies remain unknown.
      We identified two subregions of the dorsal habenula (dHb) in zebrafish that
      antagonistically regulate the outcome of conflict. The losing experience reduced
      neural transmission in the lateral subregion of dHb (dHbL)-dorsal/intermediate
      interpeduncular nucleus (d/iIPN) circuit. Silencing of the dHbL or medial
      subregion of dHb (dHbM) caused a stronger predisposition to lose or win a fight,
      respectively. These results demonstrate that the dHbL and dHbM comprise a dual
      control system for conflict resolution of social aggression. 

PMID- 27034373
TI  - A long noncoding RNA associated with susceptibility to celiac disease.
AB  - Recent studies have implicated long noncoding RNAs (lncRNAs) as regulators of
      many important biological processes. Here we report on the identification and
      characterization of a lncRNA, lnc13, that harbors a celiac disease-associated
      haplotype block and represses expression of certain inflammatory genes under
      homeostatic conditions. Lnc13 regulates gene expression by binding to hnRNPD, a
      member of a family of ubiquitously expressed heterogeneous nuclear
      ribonucleoproteins (hnRNPs). Upon stimulation, lnc13 levels are reduced, thereby
      allowing increased expression of the repressed genes. Lnc13 levels are
      significantly decreased in small intestinal biopsy samples from patients with
      celiac disease, which suggests that down-regulation of lnc13 may contribute to
      the inflammation seen in this disease. Furthermore, the lnc13 disease-associated
      variant binds hnRNPD less efficiently than its wild-type counterpart, thus
      helping to explain how these single-nucleotide polymorphisms contribute to celiac
      disease. 

PMID- 27034375
TI  - Of mice and mics.

PMID- 27034374
TI  - The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2
      immunity.
AB  - Host responses against metazoan parasites or an array of environmental substances
      elicit type 2 immunity. Despite its protective function, type 2 immunity also
      drives allergic diseases. The mechanisms that regulate the magnitude of the type
      2 response remain largely unknown. Here, we show that genetic ablation of a
      receptor tyrosine kinase encoded byTyro3in mice or the functional neutralization
      of its ortholog in human dendritic cells resulted in enhanced type 2 immunity.
      Furthermore, the TYRO3 agonist PROS1 was induced in T cells by the quintessential
      type 2 cytokine, interleukin-4. T cell-specificPros1knockouts phenocopied the
      loss ofTyro3 Thus, a PROS1-mediated feedback from adaptive immunity engages a
      rheostat, TYRO3, on innate immune cells to limit the intensity of type 2
      responses. 

PMID- 27034376
TI  - Long-read sequence assembly of the gorilla genome.
AB  - Accurate sequence and assembly of genomes is a critical first step for studies of
      genetic variation. We generated a high-quality assembly of the gorilla genome
      using single-molecule, real-time sequence technology and a string graph de novo
      assembly algorithm. The new assembly improves contiguity by two to three orders
      of magnitude with respect to previously released assemblies, recovering 87% of
      missing reference exons and incomplete gene models. Although regions of large,
      high-identity segmental duplications remain largely unresolved, this
      comprehensive assembly provides new biological insight into genetic diversity,
      structural variation, gene loss, and representation of repeat structures within
      the gorilla genome. The approach provides a path forward for the routine assembly
      of mammalian genomes at a level approaching that of the current quality of the
      human genome. 

PMID- 27034377
TI  - Programmed necrosis in inflammation: Toward identification of the effector
      molecules.
AB  - Until recently, programmed cell death was conceived of as a single set of
      molecular pathways. We now know of several distinct sets of death-inducing
      mechanisms that lead to differing cell-death processes. In one of them--apoptosis
      -the dying cell affects others minimally. In contrast, programmed necrotic cell
      death causes release of immunostimulatory intracellular components after cell
      membrane rupture. Defining the in vivo relevance of necrotic death is hampered
      because the molecules initiating it [such as receptor-interacting protein kinase
      1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that
      participate in late events in two forms of programmed necrosis [mixed lineage
      kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis]
      were recently discovered, bringing us closer to identifying molecules that
      strictly serve in death mediation, thereby providing probes for better assessing
      its role in inflammation.

PMID- 27034378
TI  - Genetic circuit design automation.
AB  - Computation can be performed in living cells by DNA-encoded circuits that process
      sensory information and control biological functions. Their construction is time
      intensive, requiring manual part assembly and balancing of regulator expression.
      We describe a design environment, Cello, in which a user writes Verilog code that
      is automatically transformed into a DNA sequence. Algorithms build a circuit
      diagram, assign and connect gates, and simulate performance. Reliable circuit
      design requires the insulation of gates from genetic context, so that they
      function identically when used in different circuits. We used Cello to design 60
      circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA
      sequence was built as predicted by the software with no additional tuning. Of
      these, 45 circuits performed correctly in every output state (up to 10 regulators
      and 55 parts), and across all circuits 92% of the output states functioned as
      predicted. Design automation simplifies the incorporation of genetic circuits
      into biotechnology projects that require decision-making, control, sensing, or
      spatial organization. 

PMID- 27034379
TI  - TP53 Is Not the Only Driver of Chromosome 17p Loss.
AB  - Deletions at the Trp53 locus drive cancer in part through co-deletion of other
      tumor suppressors.

PMID- 27034380
TI  - A Set of Transcriptomic Changes Is Associated with Anti-PD-1 Resistance.
AB  - The IPRES signature is related to anti-PD-1 response, and high mutational load
      predicts survival.

PMID- 27034381
TI  - Hepatic Deletion of AKT1 and AKT2 Induces Hepatocellular Carcinoma.
AB  - Systemic deletion of Akt1 and Akt2 is lethal in adult mice, whereas hepatic
      deletion accelerates HCC.

PMID- 27034382
TI  - Schwann Cells Promote Cancer Cell Invasion.
AB  - Schwann cell contact induces cancer cell dispersion and perineural invasion.

PMID- 27034383
TI  - Immune Checkpoint Inhibition Is Effective in Hypermutant Glioblastoma.
AB  - bMMRD GBM has a higher neoantigen load than tumors that respond to immune
      checkpoint inhibitors.

PMID- 27034386
TI  - Cytologic Criteria for Mast Cell Tumor Grading in Dogs With Evaluation of
      Clinical Outcome.
AB  - A 2-tiered histologic grading scheme for canine cutaneous mast cell tumors (MCTs)
      is based on morphologic characteristics of neoplastic cells, including
      karyomegaly, multinucleation, nuclear pleomorphism, and mitotic figures.
      Aspirates from MCTs may provide the same information more quickly, inexpensively,
      and less invasively. This study used these criteria to develop a cytologic
      grading scheme for canine MCTs to predict outcome. Three anatomic pathologists
      graded histologic samples from 152 canine MCTs. Three clinical pathologists
      evaluated aspirates from these masses using similar criteria. A cytologic grading
      scheme was created based on correlation with histologic grade and evaluated with
      a kappa statistic. Survival was evaluated with Kaplan-Meier survival curves. Cox
      proportional hazards regression was used to estimate hazard ratios for tumor
      grades and individual grading components. Simple logistic regression tested for
      relationships between risk factors and mortality. The cytologic grading scheme
      that best correlated with histology (kappa = 0.725 +/- 0.085) classified a tumor
      as high grade if it was poorly granulated or had at least 2 of 4 findings:
      mitotic figures, binucleated or multinucleated cells, nuclear pleomorphism, or
      >50% anisokaryosis. The cytologic grading scheme had 88% sensitivity and 94%
      specificity relative to histologic grading. Dogs with histologic and cytologic
      high grade MCTs were 39 times and 25 times more likely to die within the 2-year
      follow-up period, respectively, than dogs with low grade MCTs. High tumor grade
      was associated with increased probability of additional tumors or tumor regrowth.
      This study concluded that cytologic grade is a useful predictor for treatment
      planning and prognostication.

PMID- 27034387
TI  - Pathology and Epidemiology of Stillbirth in New Zealand Sea Lions (Phocarctos
      hookeri) From Enderby Island, Auckland Islands, 1998-2012.
AB  - Stillbirth is a small and often cryptic fraction of neonatal mortality in mammals
      including pinnipeds. As part of an investigation into the poor reproductive
      success of the endangered New Zealand sea lion (Phocarctos hookeri), archived
      tissues from 37 stillborn pups born on Enderby Island between 1998 and 2012 were
      examined using histopathological techniques. Apart from bronchopneumonia with
      neutrophilic infiltration in 4 cases, few inflammatory conditions were identified
      in stillborn pups. However, 27/32 (84%) stillborn pups had aspirated squames
      present in the respiratory tract, without meconium. It is unclear if this finding
      represents fetal distress during parturition or whether it is a normal finding
      for this species. Three pups lacked histological evidence of hepatic glycogen
      storage, which may indicate placental defects or maternal undernutrition. No
      evidence of infectious disease was found on histopathological analysis,
      consistent with the low seroprevalence in New Zealand of infections known to
      cause reproductive failure in other pinniped species. This study forms an
      important baseline for further examination of stillborn New Zealand sea lion
      pups, as pup mortality is investigated as a contributor to the species' decline.

PMID- 27034388
TI  - Rapid Fiber-optic Raman Spectroscopy for Real-Time In Vivo Detection of Gastric
      Intestinal Metaplasia during Clinical Gastroscopy.
AB  - We report a unique simultaneous fingerprint (FP) and high-wavenumber (HW) Raman
      spectroscopy technique coupled with a beveled fiber-optic Raman probe for
      improving in vivo detection of gastric intestinal metaplasia (IM)-precancerous
      lesions in real-time during clinical gastroscopy. A total of 4,520 high-quality
      in vivo FP/HW gastric Raman spectra (normal = 4,178; IM = 342) were acquired from
      157 gastric patients undergoing endoscopic examination. Multivariate diagnostic
      algorithms based on principal components analysis and linear discriminant
      analysis together with the leave-one tissue site-out, cross-validation on in vivo
      tissue Raman spectra yield the diagnostic sensitivities of 89.3%, 89.3%, and
      75.0%; specificities of 92.2%, 84.4%, and 82.0%; positive predictive values of
      52.1%, 35.2%, and 28.4%; and negative predictive values of 98.9%, 98.8%, and
      97.2%, respectively, by using the integrated FP/HW, FP, and HW Raman techniques
      for identifying IM from normal gastric tissue. Further, ROC curves generated show
      that the integrated FP/HW Raman technique gives the integration area under the
      ROC curve of 0.92 for IM classification, which is superior to either FP (0.89) or
      HW Raman (0.86) technique alone. This work demonstrates for the first time that
      the simultaneous FP/HW fiber-optic Raman spectroscopy has great potential to
      enhance early diagnosis of gastric precancer in vivo during routine endoscopic
      examination. Cancer Prev Res; 9(6); 476-83. (c)2016 AACR.

PMID- 27034389
TI  - Models of Virus-Induced Carcinogenesis and Oncolytic Viruses.

PMID- 27034390
TI  - Animals Models of Human T Cell Leukemia Virus Type I Leukemogenesis.
AB  - Infection with human T cell leukemia virus type I (HTLV-I) causes adult T cell
      leukemia (ATL) in a minority of infected individuals after long periods of viral
      persistence. The various stages of HTLV-I infection and leukemia development are
      studied by using several different animal models: (1) the rabbit (and mouse)
      model of persistent HTLV-I infection, (2) transgenic mice to model tumorigenesis
      by HTLV-I specific protein expression, (3) ATL cell transfers into immune
      deficient mice, and (4) infection of humanized mice with HTLV-I. After infection,
      virus replicates without clinical disease in rabbits and to a lesser extent in
      mice. Transgenic expression of both the transactivator protein (Tax) and the HTLV
      I bZIP factor (HBZ) protein have provided insight into factors important in
      leukemia/lymphoma development. To investigate factors relating to tumor spread
      and tissue invasion, a number of immune-deficient mice based on the severe
      combined immunodeficiency (SCID) or non-obese diabetic/SCID background have been
      used. Inoculation of adult T cell leukemia cell (lines) leads to lymphoma with
      osteolytic bone lesions and to a lesser degree to leukemia development. These
      mice have been used extensively for the testing of anticancer drugs and
      virotherapy. A recent development is the use of so-called humanized mice, which,
      upon transfer of CD34(+)human umbilical cord stem cells, generate human
      lymphocytes. Infection with HTLV-I leads to leukemia/lymphoma development, thus
      providing an opportunity to investigate disease development with the aid of
      molecularly cloned viruses. However, further improvements of this mouse model,
      particularly in respect to the development of adaptive immune responses, are
      necessary. 

PMID- 27034392
TI  - Role of Feline Immunodeficiency Virus in Lymphomagenesis--Going Alone or
      Colluding?
AB  - Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of
      domestic and nondomestic feline species. Infection in domestic cats leads to
      immune dysfunction via mechanisms similar to those caused by human
      immunodeficiency virus (HIV) and, as such, is a valuable natural animal model for
      acquired immunodeficiency syndrome (AIDS) in humans. An association between FIV
      and an increased incidence of neoplasia has long been recognized, with
      frequencies of up to 20% in FIV-positive cats recorded in some studies. This is
      similar to the rate of neoplasia seen in HIV-positive individuals, and in both
      species neoplasia typically requires several years to arise. The most frequently
      reported type of neoplasia associated with FIV infection is lymphoma. Here we
      review the possible mechanisms involved in FIV lymphomagenesis, including the
      possible involvement of coinfections, notably those with gamma-herpesviruses. 

PMID- 27034391
TI  - Lessons Learned from Mouse Mammary Tumor Virus in Animal Models.
AB  - Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted,
      infectious, cancer-inducing agent in the 1930s, has been used as an animal model
      for the study of retroviral infection and transmission, antiviral immune
      responses, and breast cancer and lymphoma biology. The main target cells for MMTV
      infection in vivo are cells of the immune system and mammary epithelial cells.
      Although the host mounts an immune response to the virus, MMTV has evolved
      multiple means of evading this response. MMTV causes mammary tumors when the
      provirus integrates into the mammary epithelial and lymphoid cell genome during
      viral replication and thereby activates cellular oncogene expression. Thus, tumor
      induction is a by-product of the infection cycle. A number of important oncogenes
      have been discovered by carrying out MMTV integration site analysis, some of
      which may play a role in human breast cancer. 

PMID- 27034394
TI  - Transgenic Mouse Models of SV40-Induced Cancer.
AB  - The SV40 viral oncogene has been used since the 1970s as a reliable and
      reproducible method to generate transgenic mouse models. This seminal discovery
      has taught us an immense amount about how tumorigenesis occurs, and its success
      has led to the evolution of many mouse models of cancer. Despite the development
      of more modern and targeted approaches for developing genetically engineered
      mouse models of cancer, SV40-induced mouse models still remain frequently used
      today. This review discusses a number of cancer types in which SV40 mouse models
      of cancer have been developed and highlights their relevance and importance to
      preclinical research. 

PMID- 27034393
TI  - Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and
      Use as Viral Oncology Animal Model.
AB  - Rabbits have served as a valuable animal model for the pathogenesis of various
      human diseases, including those related to agents that gain entry through the
      gastrointestinal tract such as human T cell leukemia virus type 1. However,
      limited information is available regarding the spatial distribution and
      phenotypic characterization of major rabbit leukocyte populations in mucosa
      associated lymphoid tissues. Herein, we describe the spatial distribution and
      phenotypic characterization of leukocytes from gut-associated lymphoid tissues
      (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits
      have similar distribution of leukocyte subsets as humans, both in the GALT
      inductive and effector sites and in mesenteric lymph nodes, spleen, and
      peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's
      patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from
      4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in
      all four tissues. Intraepithelial and lamina propria compartments contained
      mostly T cells, with CD4 T cells predominating in the lamina propria compartment
      and CD8 T cells predominating in the intraepithelial compartment. Mesenteric
      lymph node, peripheral blood, and splenic samples contained approximately equal
      percentages of B cells and T cells, with a high proportion of CD4 T cells
      compared with CD8 T cells. Collectively, our data indicate that New Zealand White
      rabbits are comparable with humans throughout their GALT and support future
      studies that use the rabbit model to study human gut-associated disease or
      infectious agents that gain entry by the oral route. 

PMID- 27034395
TI  - Murine Models of Epstein-Barr Virus-Associated Lymphomagenesis.
AB  - The Epstein-Barr virus (EBV) is a B-lymphotropic gamma herpes virus associated
      with a number of malignancies. Most EBV-related cancers present complex medical
      management challenges; thus it has been essential to develop preclinical in vivo
      models allowing for the study of pathogenesis, prevention, and treatment of these
      diseases. Early in vivo models used nonhuman primates; however, such models were
      limited by the inability of EBV to achieve viral latency, availability, and cost.
      Immunodeficient mouse strains emerged as efficient models that allow for
      engraftment of human mononuclear cells and controlled evaluation of EBV-driven
      lymphoproliferative disease (EBV-LPD). By using highly immunodeficient strains of
      mice such as severe combined immune deficiency (SCID) and NOD/LtSz-scid ILrg(-/
      )(NOG) mice, investigators have developed efficient platforms for evaluating
      pathogenesis of benign (HLH) and malignant (EBV-LPD) diseases associated with
      EBV. Humanized murine chimeric models have been essential tools for evaluating
      preventive strategies with vaccine and adoptive cellular approaches, as well as
      development of experimental therapeutic strategies. Manipulation of the human
      immune cells before engraftment or mutation of viral lytic and latent genes has
      enhanced our understanding of the oncogenic nature of EBV and the complexity of
      human immune responses to EBV. In this review, we discuss how the EBV murine
      models have evolved to become essential tools for studying the virology of EBV as
      it relates to human EBV-LPD pathogenesis, the immunobiology of innate and
      adaptive responses, and limitations of these models.

PMID- 27034396
TI  - Preclinical Mouse Models for Analysis of the Therapeutic Potential of Engineered
      Oncolytic Herpes Viruses.
AB  - After more than two decades of research and development, oncolytic herpes viruses
      (oHSVs) are moving into the spotlight due to recent encouraging clinical trial
      data. oHSV and other oncolytic viruses function through direct oncolytic cancer
      cell-killing mechanisms and by stimulating antitumor immunity. As further viruses
      are developed and optimized for the treatment of various types of cancer,
      appropriate predictive preclinical models will be of great utility. This review
      will discuss existing data in this area, focusing on the mouse tumor models that
      are commonly used. 

PMID- 27034398
TI  - Institutional Animal Care and Use Committee Considerations Regarding the Use of
      Virus-Induced Carcinogenesis and Oncolytic Viral Models.
AB  - The use of virus-induced carcinogenesis and oncologic experimental animal models
      is essential in understanding the mechanisms of cancer development to advance
      prevention, diagnosis, and treatment methods. The Institutional Animal Care and
      Use Committee (IACUC) is responsible for both the complex philosophical and
      practical considerations associated with animal models of cancer. Animal models
      of cancer carry their own unique issues that require special consideration from
      the IACUC. Many of the considerations to be discussed apply to cancer models in
      general; specific issues related to viral carcinogenesis or oncolytic viruses
      will be specifically discussed as they arise. Responsible animal use integrates
      good science, humane care, and regulatory compliance. To meet those standards,
      the IACUC, in conjunction with the research investigator and attending
      veterinarian, must address a wide range of issues, including animal model
      selection, cancer model selection, humane end point considerations, experimental
      considerations, postapproval monitoring, reporting requirements, and animal
      management and personnel safety considerations. 

PMID- 27034397
TI  - Murine Tumor Models for Oncolytic Rhabdo-Virotherapy.
AB  - The preclinical optimization and validation of novel treatments for cancer
      therapy requires the use of laboratory animals. Although in vitro experiments
      using tumor cell lines and ex vivo treatment of patient tumor samples provide a
      remarkable first-line tool for the initial study of tumoricidal potential, tumor
      bearing animals remain the primary option to study delivery, efficacy, and safety
      of therapies in the context of a complete tumor microenvironment and functional
      immune system. In this review, we will describe the use of murine tumor models
      for oncolytic virotherapy using vesicular stomatitis virus. We will discuss
      studies using immunocompetent and immunodeficient models with respect to toxicity
      and therapeutic treatments, as well as the various techniques and tools available
      to study cancer therapy with Rhabdoviruses. 

PMID- 27034399
TI  - HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients.
AB  - BACKGROUND AND OBJECTIVES: The current allocation algorithm for deceased donor
      kidney transplantation takes into consideration HLA mismatches at the ABDR loci
      but not HLA mismatches at other loci, including HLA-DQ. However, the independent
      effects of incompatibilities for the closely linked HLA-DQ antigens in the
      context of HLA-DR antigen matched and mismatched allografts are uncertain. We
      aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the Australia and
      New Zealand Dialysis and Transplant Registry, we examined the association between
      HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney
      transplant recipients between 2004 and 2012 using adjusted Cox regression models.
      RESULTS: Of the 788 recipients followed for a median of 2.8 years (resulting in
      2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA
      DQ mismatched kidneys, respectively. Compared with recipients who have received
      zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ
      mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus
      117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of
      321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321
      versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched
      kidneys, the adjusted hazard ratios for any and late rejections in recipients who
      had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence
      interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively.
      HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for
      interaction =0.02), such that the association between HLA-DQ mismatches and AMR
      was statistically significant in those who have received one or two HLA-DR
      mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).
      CONCLUSIONS: HLA-DQ mismatches are associated with acute rejection, independent
      of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware
      of the potential importance of HLA-DQ matching in the assessment of immunologic
      risk in kidney transplant recipients.

PMID- 27034400
TI  - Ultrafiltration Therapy for Heart Failure: Balancing Likely Benefits against
      Possible Risks.
AB  - Heart failure remains a major public health concern because of its high
      prevalence, morbidity, mortality, and financial burden. The poor clinical
      outcomes associated with acute decompensated heart failure, suboptimal efficacy
      and safety profile of conventional treatment regimens, and unsatisfactory
      experiences with the newer classes of pharmacologic therapy underlie the interest
      in the use of extracorporeal isolated ultrafiltration in this setting. In this
      article, selected mechanistic aspects of ultrafiltration therapy are briefly
      reviewed followed by a critical overview of the largest trials in this field. I
      will discuss the clinical relevance of renal dysfunction and decongestion as two
      commonly used end points of safety and efficacy in the ultrafiltration trials,
      with emphasis on the emerging pertinent notions that could challenge our
      conventional thinking. Finally, a number of practical recommendations (e.g.,
      customization of ultrafiltration rates) are provided for ultrafiltration therapy
      in the setting of acute decompensated heart failure. Because of a paucity of
      evidence, universally accepted consensus guidelines cannot yet be generated. As
      such, when considering ultrafiltration therapy for acute decompensated heart
      failure, the likely benefits should be carefully balanced against the potential
      risks for an individual patient. A conceivable implication of the ultrafiltration
      trials is that collaborative heart failure programs benefiting from nephrology
      expertise and resources could improve the outcomes and reduce the cost.

PMID- 27034401
TI  - HLA-DQ Mismatching: Mounting Evidence for a Role in Kidney Transplant Rejection.

PMID- 27034402
TI  - Sensitivity of dendritic cells to NK-mediated lysis depends on the inflammatory
      environment and is modulated by CD54/CD226-driven interactions.
AB  - Previous studies have suggested that NK cells may limit T cell responses by their
      ability to eradicate dendritic cells, as demonstrated by NK cell-mediated killing
      of dendritic cells generated from mouse bone marrow cells or human monocytes with
      GM-CSF. In the present study, we demonstrated that conventional dendritic cells,
      generated in vitro with Flt3 ligand or from spleens, were resistant to NK cell
      mediated lysis. However, upon stimulation with GM-CSF, NK cells could mediate
      lysis of these dendritic cells. GM-CSF-stimulated Flt3 ligand dendritic cells or
      splenic dendritic cells increased surface expression of costimulatory molecules
      and known NK cell ligands. Likewise, NK cells could target dendritic cells in
      vivo, which could be inhibited, in part, by anti-GM-CSF antibodies. The blocking
      of CD54 or CD226 inhibited NK cell-mediated cytotoxicity of the GM-CSF-stimulated
      Flt3 ligand conventional dendritic cells. Furthermore, the CD226+NKG2A- subset of
      NK cells was selectively better at targeting GM-CSF-stimulated Flt3 ligand
      conventional dendritic cells. However, CD155, a known ligand for CD226, could
      also act as an inhibitor of NK cell-mediated lysis, as dendritic cells lacking
      CD155 were more sensitive to NK cell-mediated lysis than wild-type dendritic
      cells. We hypothesize that by only permitting a subset of NK cells to target
      activated dendritic cells during inflammation, this would allow the immune system
      to balance between dendritic cells able to drive adaptive immune responses and
      dendritic cells targeted for elimination by NK cells to hinder, e.g., spread of
      infection.

PMID- 27034403
TI  - Human mast cells capture, store, and release bioactive, exogenous IL-17A.
AB  - IL-17A, a major proinflammatory cytokine, can be produced by a variety of
      leukocytes, but its exact cellular source in human inflammatory diseases remains
      incompletely understood. IL-17A protein is abundantly found in mast cells in
      human tissues, such as inflamed synovium, but surprisingly, mechanistic murine
      studies failed to demonstrate IL-17A production by mast cells. Here, we
      demonstrate that primary human tissue mast cells do not produce IL-17A themselves
      but actively capture exogenous IL-17A through receptor-mediated endocytosis. The
      exogenous IL-17A is stored in intracellular granules and can subsequently be
      released in a bioactive form. This novel mechanism confers to mast cells the
      capacity to steer IL-17A-mediated tissue inflammation by the rapid release of
      preformed cytokine.

PMID- 27034404
TI  - JAK/STAT regulation of Aspergillus fumigatus corneal infections and IL-6/23
      stimulated neutrophil, IL-17, elastase, and MMP9 activity.
AB  - IL-6 and IL-23 (IL-6/23) induce IL-17A (IL-17) production by a subpopulation of
      murine and human neutrophils, resulting in autocrine IL-17 activation, enhanced
      production of reactive oxygen species, and increased fungal killing. As IL-6 and
      IL-23 receptors trigger JAK1, -3/STAT3 and JAK2/STAT3 phosphorylation,
      respectively, we examined the role of this pathway in a murine model of fungal
      keratitis and also examined neutrophil elastase and gelatinase (matrix
      metalloproteinase 9) activity by IL-6/23-stimulated human neutrophils in vitro.
      We found that STAT3 phosphorylation of neutrophils in Aspergillus fumigatus
      infected corne as was inhibited by the JAK/STAT inhibitor Ruxolitinib, resulting
      in impaired fungal killing and decreased matrix metalloproteinase 9 activity. In
      vitro, we showed that fungal killing by IL-6/23-stimulated human peripheral blood
      neutrophils was impaired by JAK/STAT inhibitors Ruxolitinib and Stattic, and by
      the retinoic acid receptor-related orphan receptor gammat inhibitor SR1001. This
      was also associated with decreased reactive oxygen species, IL-17A production,
      and retinoic acid receptor-related orphan receptor gammat translocation to the
      nucleus. We also demonstrate that IL-6/23-activated neutrophils exhibit increased
      elastase and gelatinase (matrix metalloproteinase 9) activity, which is inhibited
      by Ruxolitinib and Stattic but not by SR1001. Taken together, these observations
      indicate that the regulation of activity of IL-17-producing neutrophils by
      JAK/STAT inhibitors impairs reactive oxygen species production and fungal killing
      activity but also blocks elastase and gelatinase activity that can cause tissue
      damage.

PMID- 27034406
TI  - Workplace Discrimination Is Associated With Alcohol Abuse Among Ethnically
      Diverse Hospital Staff.
AB  - Research suggests that workplace discrimination plays a role in absenteeism,
      productivity, and turnover. A link among workplace discrimination, mental health,
      and health disparities may also exist. The purpose of this study was to determine
      whether self-reported workplace discrimination is associated with alcohol abuse
      among hospital workers. Cross-sectional analysis of baseline data collected from
      a prospective cohort study of workers in two healthcare institutions (n = 664)
      was conducted. Workplace discrimination in the previous 12 months was reported by
      14% (n = 91) of participants who were four times more likely to score higher on
      likely alcohol abuse than their peers. White participants who reported any
      discrimination were more likely to score higher on likely alcohol abuse than
      racial/ethnic minority participants who reported any discrimination. Given a
      diversifying workforce, further research is needed on how workplace
      discrimination contributes to stress and maladaptive coping, and ultimately
      health disparities. 

PMID- 27034405
TI  - Human MAIT-cell responses to Escherichia coli: activation, cytokine production,
      proliferation, and cytotoxicity.
AB  - Mucosa-associated invariant T cells are a large and relatively recently described
      innate-like antimicrobial T-cell subset in humans. These cells recognize
      riboflavin metabolites from a range of microbes presented by evolutionarily
      conserved major histocompatibility complex, class I-related molecules. Given the
      innate-like characteristics of mucosa-associated invariant T cells and the novel
      type of antigens they recognize, new methodology must be developed and existing
      methods refined to allow comprehensive studies of their role in human immune
      defense against microbial infection. In this study, we established protocols to
      examine a range of mucosa-associated invariant T-cell functions as they respond
      to antigen produced by Escherichia coli These improved and dose- and time
      optimized experimental protocols allow detailed studies of MR1-dependent mucosa
      associated invariant T-cell responses to Escherichia coli pulsed antigen
      presenting cells, as assessed by expression of activation markers and cytokines,
      by proliferation, and by induction of apoptosis and death in major
      histocompatibility complex, class I-related-expressing target cells. The novel
      and optimized protocols establish a framework of methods and open new
      possibilities to study mucosa-associated invariant T-cell immunobiology, using
      Escherichia coli as a model antigen. Furthermore, we propose that these robust
      experimental systems can also be adapted to study mucosa-associated invariant T
      cell responses to other microbes and types of antigen-presenting cells.

PMID- 27034407
TI  - Determinants of General Health, Work-Related Strain, and Burnout in Public Versus
      Private Emergency Medical Technicians in Istanbul.
AB  - This study investigated the impact of working for public versus private ambulance
      services in Turkey and elaborated on predictors of mental, physical, and
      emotional well-being in emergency medical technicians (EMT-Bs). In this
      observational cross-sectional study, an 81-question self-report survey was used
      to gather data about employee demographics, socioeconomic status, educational
      background, working conditions, and occupational health and workplace safety
      (OHS), followed by the 12-item General Health Questionnaire (GHQ-12), the Work
      Related Strain Inventory (WRSI), and the Maslach Burnout Inventory (MBI) with
      three subscales: Emotional Exhaustion (MBI-EE), Depersonalization (MBI-DP), and
      Diminished Personal Accomplishment (MBI-PA). In 2011, 1,038 EMT-Bs worked for
      publicly operated and 483 EMT-Bs worked for privately owned ambulance services in
      Istanbul, Turkey, of which 606 (58.4%) and 236 (48.9%) participated in the study
      (overall participation rate = 55.4%), respectively. On all scales, differences
      between total mean scores in both sectors were statistically insignificant (p >
      .05). In the public sector, work locations, false accusations, occupational
      injuries and diseases, work-related permanent disabilities, and organizational
      support were found to significantly influence self-reported perceptions of well
      being (p < .05). In the private sector, commute time to and from work (p < .05),
      false accusations (p < .05), vocational training and education (p < .05),
      informed career choices (p < .05), and work-related permanent disabilities (p <
      .05) were found to significantly influence self-reported perceptions of well
      being. EMT-Bs were asked about aspects of their working lives that need
      improvement; priority expectations in the public and private sectors were higher
      earnings (17.5%; 16.7%) and better social opportunities (17.4%; 16.8%). Working
      conditions, vocational training, and OHS emerged as topics that merit priority
      attention. 

PMID- 27034408
TI  - Correction for Pedersen et al., Regulation of CARD11 Signaling and Lymphoma Cell
      Survival by the E3 Ubiquitin Ligase RNF181.

PMID- 27034410
TI  - Functional and Transcriptional Characterization of Histone Deacetylase Inhibitor
      Mediated Cardiac Adverse Effects in Human Induced Pluripotent Stem Cell-Derived
      Cardiomyocytes.
AB  - Histone deacetylase (HDAC) inhibitors possess therapeutic potential to reverse
      aberrant epigenetic changes associated with cancers, neurological diseases, and
      immune disorders. Unfortunately, clinical studies with some HDAC inhibitors
      displayed delayed cardiac adverse effects, such as atrial fibrillation and
      ventricular tachycardia. However, the underlying molecular mechanism(s) of HDAC
      inhibitor-mediated cardiotoxicity remains poorly understood and is difficult to
      detect in the early stages of preclinical drug development because of a delayed
      onset of effects. In the present study, we show for the first time in human
      induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) that HDAC
      inhibitors (dacinostat, panobinostat, vorinostat, entinostat, and tubastatin-a)
      induce delayed dose-related cardiac dysfunction at therapeutic concentrations
      associated with cardiac adverse effects in humans. HDAC inhibitor-mediated
      delayed effects on the beating properties of hiPS-CMs developed after 12 hours by
      decreasing the beat rate, shortening the field potential duration, and inducing
      arrhythmic behavior under form of sustained contractions and fibrillation-like
      patterns. Transcriptional changes that are common between the cardiotoxic HDAC
      inhibitors but different from noncardiotoxic treatments identified cardiac
      specific genes and pathways related to structural and functional changes in
      cardiomyocytes. Combining the functional data with epigenetic changes in hiPS-CMs
      allowed us to identify molecular targets that might explain HDAC inhibitor
      mediated cardiac adverse effects in humans. Therefore, hiPS-CMs represent a
      valuable translational model to assess HDAC inhibitor-mediated cardiotoxicity and
      support identification of better HDAC inhibitors with an improved benefit-risk
      profile. SIGNIFICANCE: Histone deacetylase (HDAC) inhibitors are a promising
      class of drugs to treat certain cancers, autoimmune, and neurodegenerative
      diseases. However, treated patients can experience various cardiac adverse events
      such as hearth rhythm disorders. This study found that human induced pluripotent
      stem cell-derived cardiomyocytes (hiPS-CMs) can predict cardiac adverse events in
      patients caused by HDAC inhibitors. Furthermore, transcriptional changes at the
      level of gene expression supported the effects on the beating properties of hiPS
      CMs and highlight targets that might cause these cardiac adverse effects. hiPS
      CMs represent a valuable translational model to assess HDAC inhibitor-mediated
      cardiotoxicity and to support development of safer HDAC inhibitors.

PMID- 27034411
TI  - Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic
      Ductal Epithelial Cells.
AB  - We established an efficient strategy to direct human pluripotent stem cells,
      including human embryonic stem cells (hESCs) and an induced pluripotent stem cell
      (iPSC) line derived from patients with cystic fibrosis, to differentiate into
      pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of
      hESC-derived PDECs expressed functional cystic fibrosis transmembrane conductance
      regulator (CFTR) protein. In addition, iPSC lines were derived from a patient
      with CF carrying compound frameshift and mRNA splicing mutations and were
      differentiated to PDECs. PDECs derived from Weill Cornell cystic fibrosis (WCCF)
      iPSCs showed defective expression of mature CFTR protein and impaired chloride
      ion channel activity, recapitulating functional defects of patients with CF at
      the cellular level. These studies provide a new methodology to derive pure PDECs
      expressing CFTR and establish a "disease in a dish" platform to identify drug
      candidates to rescue the pancreatic defects of patients with CF. SIGNIFICANCE: An
      efficient strategy was established to direct human pluripotent stem cells,
      including human embryonic stem cells (hESCs) and an induced pluripotent stem cell
      line derived from patients with cystic fibrosis (CF-iPSCs), to differentiate into
      pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of
      hESC-PDECs derived from CF-iPSCs showed defective expression of mature cystic
      fibrosis transmembrane conductance regulator (CFTR) protein and impaired chloride
      ion channel activity, recapitulating functional pancreatic defects of patients
      with CF at the cellular level. These studies provide a new methodology for
      deriving pure PDECs expressing CFTR, and they establish a "disease-in-a-dish"
      platform for identifying drug candidates to rescue the pancreatic defects of
      these patients.

PMID- 27034414
TI  - Frei E III, Holland JF, Schneiderman MA, et al. A comparative study of two
      regimens of combination chemotherapy in acute leukemia. Blood. 1958;13(12):1126
      1148.
AB  - This article presents one of the first cooperative multicenter comparative trials
      in modern clinical oncology. The authors introduce the innovative concept of
      combination chemotherapy consisting of 2 antimetabolites and a corticosteroid.
      Two schedules were prospectively compared. Randomizing patients was also novel,
      and the ethical issues are discussed. In those days, acute myeloid leukemia and
      acute lymphoblastic leukemia (ALL) could not be distinguished, and the same
      treatment was applied to both. Remarkably, survival was better for patients
      responding to chemotherapy. Many of these authors continued their seminal
      contributions to developmental cancer therapy, and one (Donald Pinkel) would
      pioneer the successful "total therapy" for pediatric ALL.

PMID- 27034413
TI  - Massive Clonal Selection and Transiently Contributing Clones During Expansion of
      Mesenchymal Stem Cell Cultures Revealed by Lentiviral RGB-Barcode Technology.
AB  - Mesenchymal stem (or stromal) cells (MSCs) have been used in more than 400
      clinical trials for the treatment of various diseases. The clinical benefit and
      reproducibility of results, however, remain extremely variable. During the in
      vitro expansion phase, which is necessary to achieve clinically relevant cell
      numbers, MSCs show signs of aging accompanied by different contributions of
      single clones to the mass culture. Here we used multicolor lentiviral barcode
      labeling to follow the clonal dynamics during in vitro MSC expansion from whole
      umbilical cord pieces (UCPs). The clonal composition was analyzed by a
      combination of flow cytometry, fluorescence microscopy, and deep sequencing.
      Starting with highly complex cell populations, we observed a massive reduction in
      diversity, transiently dominating populations, and a selection of single clones
      over time. Importantly, the first wave of clonal constriction already occurred in
      the early passages during MSC expansion. Consecutive MSC cultures from the same
      UCP implied the existence of more primitive, MSC culture-initiating cells. Our
      results show that microscopically homogenous MSC mass cultures consist of many
      subpopulations, which undergo clonal selection and have different capabilities.
      Among other factors, the clonal composition of the graft might have an impact on
      the functional properties of MSCs in experimental and clinical settings.
      SIGNIFICANCE: Mesenchymal stem cells (MSCs) can easily be obtained from various
      adult or embryonal tissues and are frequently used in clinical trials. For their
      clinical application, MSCs have to be expanded in vitro. This unavoidable step
      influences the features of MSCs, so that clinical benefit and experimental
      results are often highly variable. Despite a homogenous appearance under the
      microscope, MSC cultures undergo massive clonal selection over time. Multicolor
      fluorescence labeling and deep sequencing were used to demonstrate the dynamic
      clonal composition of MSC cultures, which might ultimately explain the variable
      clinical performance of the cells.

PMID- 27034412
TI  - High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds
      That Protect Against Oxidative Stress.
AB  - Astrocytes are the predominant cell type in the nervous system and play a
      significant role in maintaining neuronal health and homeostasis. Recently,
      astrocyte dysfunction has been implicated in the pathogenesis of many
      neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease,
      Huntington's disease, and amyotrophic lateral sclerosis. Astrocytes are thus an
      attractive new target for drug discovery for neurological disorders. Using
      astrocytes differentiated from human embryonic stem cells, we have developed an
      assay to identify compounds that protect against oxidative stress, a condition
      associated with many neurodegenerative diseases. This phenotypic oxidative stress
      assay has been optimized for high-throughput screening in a 1,536-well plate
      format. From a screen of approximately 4,100 bioactive tool compounds and
      approved drugs, we identified a set of 22 that acutely protect human astrocytes
      from the consequences of hydrogen peroxide-induced oxidative stress. Nine of
      these compounds were also found to be protective of induced pluripotent stem cell
      differentiated astrocytes in a related assay. These compounds are thought to
      confer protection through hormesis, activating stress-response pathways and
      preconditioning astrocytes to handle subsequent exposure to hydrogen peroxide. In
      fact, four of these compounds were found to activate the antioxidant response
      element/nuclear factor-E2-related factor 2 pathway, a protective pathway induced
      by toxic insults. Our results demonstrate the relevancy and utility of using
      astrocytes differentiated from human stem cells as a disease model for drug
      discovery and development. SIGNIFICANCE: Astrocytes play a key role in
      neurological diseases. Drug discovery efforts that target astrocytes can identify
      novel therapeutics. Human astrocytes are difficult to obtain and thus are
      challenging to use for high-throughput screening, which requires large numbers of
      cells. Using human embryonic stem cell-derived astrocytes and an optimized
      astrocyte differentiation protocol, it was possible to screen approximately 4,100
      compounds in titration to identify 22 that are cytoprotective of astrocytes. This
      study is the largest-scale high-throughput screen conducted using human
      astrocytes, with a total of 17,536 data points collected in the primary screen.
      The results demonstrate the relevancy and utility of using astrocytes
      differentiated from human stem cells as a disease model for drug discovery and
      development.

PMID- 27034415
TI  - Hemophilia A treatment: disruptive technology ahead.
AB  - In this issue of Blood, Uchida et al report the first-in-human use of a new
      nonsubstitutive therapy for hemophilia A that can potentially be disruptive to
      the way hemophilia is treated.

PMID- 27034416
TI  - Finding partners to play the music of regulation.
AB  - In this issue of Blood, Wilson et al generate and analyze a treasure trove of
      epigenetic data, such as transcription factor occupancy, histone modifications,
      and chromatin interaction frequencies, genome-wide (ie, epigenomic data), in a
      cell line model of hematopoietic stem/progenitor cells (HSPCs). To appreciate the
      importance of these data, consider an analogy of gene expression being a song or
      symphony (transcripts) played by musicians (transcription factors and
      transcriptional machinery) reading the score encoded in the genome sequence.
      Previous studies revealed the positions of a few transcription factors across the
      genome, so we only knew about, for example, the violinists and oboists. No wonder
      we did not understand how the music was being generated (how expression was
      regulated). By mapping the sites of occupancy of many more transcription factors
      (now a total of 29), as well as positions of 4 histone modifications and DNase
      hypersensitive sites, Wilson et al reveal many more of the players and their
      partners. Furthermore, their data on 3-dimensional interaction frequencies of
      chromatin show how groups of musicians (protein complexes) come together in an
      orchestra to read the score and perform a symphony.

PMID- 27034417
TI  - Alleviating the storm: ruxolitinib in HLH.
AB  - In this issue of Blood, Das and colleagues report their results on the use of the
      Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib in murine models of
      hemophagocytic lymphohistiocytosis (HLH), and the HLH-sibling macrophage
      activation syndrome (MAS).

PMID- 27034418
TI  - A STAT3 decoy lures AML out of hiding.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) is perhaps best known for its prosurvival effects in a wide variety of
      cancers, but for some, including acute myeloid leukemia (AML), its role in immune
      evasion may be just as important. In this issue of Blood, Zhang et al report the
      development of an engineered STAT3 decoy oligodeoxynucleotide (dODN) that is
      stable in serum, is taken up specifically by target cells, and exerts its
      antileukemia effects largely by restoring the host anti-AML immune response.

PMID- 27034419
TI  - CLEC-2 and podoplanin, partners again.
AB  - In this issue of Blood, Tamura et al reveal a novel function for podoplanin on
      periarteriolar stromal cells in the bone marrow: promoting megakaryocyte growth
      and proplatelet formation by interaction with C-type lectin-like receptor 2 (CLEC
      2).

PMID- 27034420
TI  - Long-awaited news for hepatic veno-occlusive disease.
AB  - In this issue of Blood, Palomo et al provide new insight into the mechanism of
      action of defibrotide as an endothelial protective agent, while Richardson et al
      present the encouraging final results of the phase 3 clinical study of
      defibrotide for the treatment of severe hepatic veno-occlusive disease (VOD),
      showing a 23% improvement in day +100 survival after hematopoietic cell
      transplantation (HCT) compared with historical control.

PMID- 27034421
TI  - What mechanisms of tau protein transport could be responsible for the inverted
      tau concentration gradient in degenerating axons?
AB  - In tauopathies, such as Alzheimer's disease (AD), microtubule (MT)-associated
      protein tau detaches from MTs and aggregates, eventually forming insoluble
      neurofibrillary tangles. In a healthy axon, the tau concentration increases
      toward the axon terminal, but in a degenerating axon, the tau concentration
      gradient is inverted and the highest tau concentration is in the soma. In this
      article, we developed a mathematical model of tau transport in axons. We
      calibrated and tested the model by using published distributions of tau
      concentration and tau average velocity in a healthy axon. According to published
      research, the inverted tau concentration gradient may be one of the reasons
      leading to AD. We therefore used the model to investigate what modifications in
      tau transport can lead to the inverted tau concentration gradient. We
      investigated whether tau detachment from MTs due to tau hyperphosphorylation can
      cause the inverted tau concentration gradient. We found that the assumption that
      most tau molecules are detached from MTs does not consistently predict the
      inverted tau concentration gradient; the predicted tau distribution becomes more
      uniform if the axon length is increased. We then hypothesized that in
      degenerating axons some tau remains bound to MTs and participates in the
      component 'a' of slow axonal transport but that the rate of tau reversals from
      anterograde to retrograde motion increases. We demonstrated that this hypothesis
      results in a tau distribution where the tau concentration has its maximum value
      at the axon hillock and its minimum value at the axon terminal, in agreement with
      what is observed in AD. Our results thus suggest that defects in active transport
      of tau may be a contributing factor to the onset of neural degeneration.

PMID- 27034422
TI  - Spatial modelling of tumour drug resistance: the case of GIST liver metastases.
AB  - This work is devoted to modelling gastrointestinal stromal tumour metastases to
      the liver, their growth and resistance to therapies. More precisely, resistance
      to two standard treatments based on tyrosine kinase inhibitors (imatinib and
      sunitinib) is observed clinically. Using observations from medical images (CT
      scans), we build a spatial model consisting in a set of non-linear partial
      differential equations. After calibration of its parameters with clinical data,
      this model reproduces qualitatively and quantitatively the spatial tumour
      evolution of one specific patient. Important features of the growth such as the
      appearance of spatial heterogeneities and the therapeutical failures may be
      explained by our model. We then investigate numerically the possibility of
      optimizing the treatment in terms of progression-free survival time and minimum
      tumour size reachable by varying the dose of the first treatment. We find that
      according to our model, the progression-free survival time reaches a plateau with
      respect to this dose. We also demonstrate numerically that the spatial structure
      of the tumour may provide much more insights on the cancer cell activities than
      the standard RECIST criteria, which only consists in the measurement of the
      tumour diameter. Finally, we discuss on the non-predictivity of the model using
      only CT scans, in the sense that the early behaviour of the lesion is not
      sufficient to predict the response to the treatment.

PMID- 27034423
TI  - Molecular control of two novel migratory paths for CGE-derived interneurons in
      the developing mouse brain.
AB  - GABAergic interneurons are highly heterogeneous and originate in the subpallium
      mainly from the medial (MGE) and caudal (CGE) ganglionic eminences according to a
      precise temporal sequence. MGE-derived cells disperse dorsally and migrate
      towards all regions of the cortex, but little is known about how CGE-derived
      cells reach their targets during development. Here, we unravel the existence of
      two novel CGE caudo-rostral migratory streams, one located laterally (LMS) and
      the other one more medially (MMS), that, together with the well-known caudal
      migratory stream (CMS), contribute to populate the neocortex, hippocampus and
      amygdala. These paths appear in a precise temporal sequence and express a
      distinct combination of transcription factors, such as SP8, PROX1, COUP-TFI and
      COUP-TFII. By inactivating COUP-TFI in developing interneurons, the lateral and
      medial streams are perturbed and expression of SP8 and COUP-TFII affected. As a
      consequence, adult mutant neocortices have laminar-specific alterations of
      distinct cortical interneuron subtypes. Overall, we propose that the existence of
      spatially and temporally regulated migratory paths in the subpallium contributes
      to the laminar distribution and specification of distinct interneuron
      subpopulations in the adult brain.

PMID- 27034424
TI  - Reiterative expression of pax1 directs pharyngeal pouch segmentation in medaka.
AB  - A striking characteristic of vertebrate development is the pharyngeal arches,
      which are a series of bulges on the lateral surface of the head of vertebrate
      embryos. Although each pharyngeal arch is segmented by the reiterative formation
      of endodermal outpocketings called pharyngeal pouches, the molecular network
      underlying the reiterative pattern remains unclear. Here, we show that pax1 plays
      crucial roles in pouch segmentation in medaka (Oryzias latipes) embryos.
      Importantly, pax1 expression in the endoderm prefigures the location of the next
      pouch before the cells bud from the epithelium. TALEN-generated pax1 mutants did
      not form pharyngeal pouches posterior to the second arch. Segmental expression of
      tbx1 and fgf3, which play essential roles in pouch development, was almost non
      existent in the pharyngeal endoderm of pax1 mutants, with disturbance of the
      reiterative pattern of pax1 expression. These results suggest that pax1 plays a
      key role in generating the primary pattern for segmentation in the pharyngeal
      endoderm by regulating tbx1 and fgf3 expression. Our findings illustrate the
      crucial roles of pax1 in vertebrate pharyngeal segmentation and provide insights
      into the evolutionary origin of the deuterostome gill slit.

PMID- 27034426
TI  - Factors associated with consistent condom use among internally displaced women in
      Leogane, Haiti: results from a cross-sectional tablet-based survey.
AB  - OBJECTIVES: Scant research has examined factors associated with condom use among
      internally displaced women in postdisaster settings, such as in postearthquake
      Haiti. The study objective was to examine social ecological factors associated
      with consistent condom use among internally displaced women in postearthquake
      Haiti. METHODS: A cross-sectional survey was conducted in 2012 with a peer-driven
      recruitment sample of internally displaced women in Leogane, Haiti. Peer health
      workers administered tablet-based structured interviews to a convenience sample
      of 175 internally displaced women. RESULTS: The 128 participants who reported
      being sexually active in the last 4 weeks were included in the analyses. Two
      thirds (65.2%) reported consistent condom use in the last month. In multivariate
      logistic regression analyses controlled for age and income, participants that
      reported sex work, depression, higher number of sex partners and shorter
      relationship duration had lower odds of consistent condom use in the past month.
      Participants who reported no experiences of intimate partner violence, lower self
      rated health, higher sexual relationship power and more meals per day, had a
      higher likelihood of reporting consistent condom use. CONCLUSIONS: This research
      provides the first assessment of contextual factors associated with consistent
      condom use among women displaced from a natural disaster such as Haiti's 2010
      earthquake. Findings demonstrate the importance of social ecological approaches
      to understand intrapersonal (eg, sex work and depression), interpersonal (eg,
      relationship power, intimate partner violence and relationship duration) and
      structural (eg, food insecurity) factors associated with internally displaced
      women's condom use. Results can inform future sexual health research and
      interventions in international disaster contexts. TRIAL REGISTRATION NUMBER:
      NCT01492829, pre-results.

PMID- 27034425
TI  - Are There Rab GTPases in Archaea?
AB  - A complex endomembrane system is one of the hallmarks of Eukaryotes. Vesicle
      trafficking between compartments is controlled by a diverse protein repertoire,
      including Rab GTPases. These small GTP-binding proteins contribute identity and
      specificity to the system, and by working as molecular switches, trigger multiple
      events in vesicle budding, transport, and fusion. A diverse collection of Rab
      GTPases already existed in the ancestral Eukaryote, yet, it is unclear how such
      elaborate repertoire emerged. A novel archaeal phylum, the Lokiarchaeota,
      revealed that several eukaryotic-like protein systems, including small GTPases,
      are present in Archaea. Here, we test the hypothesis that the Rab family of small
      GTPases predates the origin of Eukaryotes. Our bioinformatic pipeline detected
      multiple putative Rab-like proteins in several archaeal species. Our analyses
      revealed the presence and strict conservation of sequence features that
      distinguish eukaryotic Rabs from other small GTPases (Rab family motifs), mapping
      to the same regions in the structure as in eukaryotic Rabs. These mediate Rab
      specific interactions with regulators of the REP/GDI (Rab Escort Protein/GDP
      dissociation Inhibitor) family. Sensitive structure-based methods further
      revealed the existence of REP/GDI-like genes in Archaea, involved in isoprenyl
      metabolism. Our analysis supports a scenario where Rabs differentiated into an
      independent family in Archaea, interacting with proteins involved in membrane
      biogenesis. These results further support the archaeal nature of the eukaryotic
      ancestor and provide a new insight into the intermediate stages and the
      evolutionary path toward the complex membrane-associated signaling circuits that
      characterize the Ras superfamily of small GTPases, and specifically Rab proteins.

PMID- 27034427
TI  - Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With
      Progressive Central Nervous System Involvement.
AB  - Hereditary spastic paraplegias are a clinically and genetically heterogeneous
      group of disorders characterized by lower extremity spasticity and weakness.
      Recently, the first de novo mutations in KIF1A were identified in patients with
      an early-onset severe form of complicated hereditary spastic paraplegia. We
      report two additional patients with novel de novo mutations in KIF1A, hereby
      expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia.
      Both children presented with spastic paraplegia and additional findings of optic
      nerve atrophy, structural brain abnormalities, peripheral neuropathy,
      cognitive/language impairment, and never achieved ambulation. In particular, we
      highlight the progressive nature of cerebellar involvement as captured on
      sequential magnetic resonance images (MRIs), thus linking the neurodegenerative
      and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2
      identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q)
      and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to
      expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia
      caused by mutations in KIF1A.

PMID- 27034428
TI  - Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine
      hemophilia A.
AB  - Inflammatory signals such as pathogen- and danger-associated molecular patterns
      have been hypothesized as risk factors for the initiation of the anti-factor VIII
      (FVIII) immune response seen in 25% to 30% of patients with severe hemophilia A
      (HA). In these young patients, vaccines may be coincidentally administered in
      close proximity with initial exposure to FVIII, thereby providing a source of
      such stimuli. Here, we investigated the effects of 3 vaccines commonly used in
      pediatric patients on FVIII immunogenicity in a humanized HA murine model with
      variable tolerance to recombinant human FVIII (rhFVIII). Mice vaccinated
      intramuscularly against the influenza vaccine prior to multiple infusions of
      rhFVIII exhibited a decreased incidence of rhFVIII-specific neutralizing and
      nonneutralizing antibodies. Similar findings were observed with the addition of
      an adjuvant. Upon exposure to media from influenza- or FVIII-stimulated lymph
      node or splenic lymphocytes, naive CD4(+) lymphocytes preferentially migrated
      toward media from influenza-stimulated cells, indicating that antigen
      competition, by means of lymphocyte recruitment to the immunization site, is a
      potential mechanism for the observed decrease in FVIII immunogenicity. We also
      observed no differences in incidence or titer of rhFVIII-specific antibodies and
      inhibitors in mice exposed to the live-attenuated measles-mumps-rubella vaccine
      regardless of route of administration. Together, our results suggest that
      concomitant FVIII exposure and vaccination against influenza does not increase
      the risk of inhibitor formation and may in fact decrease anti-FVIII immune
      responses.

PMID- 27034429
TI  - A transplant "immunome" screening platform defines a targetable epitope
      fingerprint of multiple myeloma.
AB  - Multiple myeloma (MM) is a hematological cancer for which immune-based treatments
      are currently in development. Many of these rely on the identification of highly
      disease-specific, strongly and stably expressed antigens. Here, we profiled the
      myeloma B-cell immunome both to explore its predictive role in the context of
      autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and to
      identify novel immunotherapeutic targets. We used random peptide phage display,
      reverse immunization, and next-generation sequencing-assisted antibody phage
      display to establish a highly myeloma-specific epitope fingerprint targeted by B
      cell responses of 18 patients in clinical remission. We found that allogeneic
      HSCT more efficiently allowed production of myeloma-specific antibodies compared
      with autologous HSCT and that a highly reactive epitope recognition signature
      correlated with superior response to treatment. Next, we performed myeloma cell
      surface screenings of phage-displayed patient transplant immunomes. Although some
      of the screenings yielded clear-cut surface binders, the majority of screenings
      did not, suggesting that many of the targeted antigens may in fact not be
      accessible to the B-cell immune system in untreated myeloma cells. This fit well
      with the identification of heat-shock proteins as a class of antigens that showed
      overall the broadest reactivity with myeloma patient sera after allogeneic HSCT
      and that may be significantly translocated to the cell surface upon treatment as
      a result of immunogenic cell death. Our data reveal a disease-specific epitope
      signature of MM that is predictive for response to treatment. Mining of
      transplant immunomes for strong myeloma surface binders may open up avenues for
      myeloma immunotherapy.

PMID- 27034430
TI  - First report of MYD88 L265P somatic mutation in IgM-associated light-chain
      amyloidosis.

PMID- 27034431
TI  - Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical
      coronary stenosis in patients with STEMI.

PMID- 27034432
TI  - Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R
      mutations and subgroup sensitivity to JAK inhibitors.
AB  - In this study, we analyzed RNA-sequencing data of 14 samples characterized by
      biallelic CEBPA (CEBPA(bi)) mutations included in the Leucegene collection of 415
      primary acute myeloid leukemia (AML) specimens, and describe for the first time
      high frequency recurrent mutations in the granulocyte colony-stimulating factor
      receptor gene CSF3R, which signals through JAK-STAT proteins. Chemical
      interrogation of these primary human specimens revealed a uniform and specific
      sensitivity to all JAK inhibitors tested irrespective of their CSF3R mutation
      status, indicating a general sensitization of JAK-STAT signaling in this leukemia
      subset. Altogether, these results identified the co-occurrence of mutations in
      CSF3R and CEBPA in a well-defined AML subset, which uniformly responds to JAK
      inhibitors and paves the way to personalized clinical trials for this disease.

PMID- 27034433
TI  - Incidence of Delirium Among Patients Having Cancer Injected With Different
      Opioids for the First Time.
AB  - BACKGROUND: Despite the risk of drug-induced delirium, it is difficult to avoid
      the use of opioids in palliative care. However, no previous study has carefully
      investigated how the development of delirium varies among patients injected with
      different opioids for the first time. OBJECTIVES: To reveal the difference in the
      incidence of delirium between different opioids. DESIGN: The incidence of
      delirium was compared among 114 patients who had started morphine, oxycodone, or
      fentanyl injection at Shizuoka Cancer Center between June 2012 and September
      2014. RESULTS: The incidence of delirium was 28.9% in the morphine group (n =
      38), 19.5% in the oxycodone group (n = 41), and 8.6% in the fentanyl group (n =
      35). There was a significant difference between the morphine and fentanyl groups
      (Fisher's exact test, P = 0.04) but not between the morphine and oxycodone groups
      (P = 0.43) nor between the oxycodone and fentanyl groups (P = 0.21). CONCLUSIONS:
      The incidence of delirium after the commencement of fentanyl injection was
      significantly lower, suggesting that fentanyl is a useful opioid injection drug
      from the perspective of delirium risk.

PMID- 27034435
TI  - Exploring Nurse Communication About Spirituality.
AB  - OBJECTIVE: Although spiritual care is considered one of the pillars of palliative
      care, many health-care providers never receive formal training on how to
      communicate about spirituality with patients and families. The aim of this study
      was to explore the spiritual care experiences of oncology nurses in order to
      learn more about patient needs and nurse responses. METHODS: A survey was
      circulated at a communication training course for oncology nurses in June 2015.
      Nurses recalled a care experience that included the initiation of a spiritual
      care topic and their response to the patient/family. Data were analyzed using
      thematic analysis. RESULTS: Nurses reported that communication about spirituality
      was primarily initiated by patients, rather than family members, and spiritual
      topics commonly emerged during the end of life or when patients experienced
      spiritual distress. Nurses' experiences highlighted the positive impact spiritual
      conversations had on the quality of patient care and its benefit to families.
      Spiritual communication was described as an important nursing role at the end of
      patients' lives, and nonverbal communication, listening, and discussing patients'
      emotions were emphasized as important and effective nurse communication skills
      during spiritual care conversations. Approximately one-third of nurses in the
      sample reported sharing their own personal spiritual or religious backgrounds
      with patients, and they reported that these sharing experiences strengthened
      their own faith. CONCLUSION: It is evident that patients want to discuss
      spiritual topics during care. Study findings illustrate the need to develop a
      spiritual communication curriculum and provide spiritual care communication
      training to clinicians.

PMID- 27034434
TI  - Caring About Residents' Experiences and Symptoms (CARES) Program: A Model of
      Palliative Care Consultation in the Nursing Home.
AB  - OBJECTIVES: To describe the CARES program, a model of palliative care for nursing
      home residents. DESIGN: Descriptive analysis of the Caring About Residents'
      Experiences and Symptoms (CARES) Program that provides palliative care services
      to nursing home residents. PROGRAM EVALUATION: The CARES Program serves as an
      example of collaborative efforts to meet community needs. To evaluate the
      program, we document the services provided as well as process outcomes (changes
      to care plans, hospitalizations, location of death, and hospice utilization) for
      residents referred. RESULTS: 170 nursing home residents were seen by CARES
      Program between February 2013 to December 2015, 48% for skilled services, and 52%
      for long term care. Majority of referrals were for goals of care and concurrent
      symptom management. Following consultation, 67% of residents had a change in code
      status. Of residents desiring a palliative course 90% were never hospitalized.
      Overall, 53% of residents died; and those in long term care dying more often with
      hospice. CONCLUSION: The CARES program of palliative consultation addresses the
      needs of nursing home residents. The model has potential to be reproducible in in
      other communities.

PMID- 27034436
TI  - Decision-Making of Patients With Implantable Cardioverter-Defibrillators at End
      of Life: Family Members' Experiences.
AB  - INTRODUCTION: Many patients with advanced heart failure (HF) experience the life
      extending benefits of implantable cardioverter-defibrillators (ICD), but at the
      end stage of HF, patients may experience shocks with increasing frequency and
      change the plan for end-of-life (EOL) care including the deactivation of the ICD.
      This report describes family members' experiences of patients with ICD making
      decisions at EOL. Understanding the decision-making of patients with ICD at EOL
      can promote informed decision-making and improve the quality of EOL care.
      METHODS: This pilot study used a mixed methods approach to test the effects of a
      nurse-guided discussion in decision-making about ICD deactivation (turning off
      the defibrillation function) at the EOL. Interviews were conducted, audiotaped,
      and transcribed in 2012 to 2013 with 6 family members of patients with advanced
      HF and ICDs. Three researchers coded the data and identified themes in 2014.
      RESULTS: Three main themes described family members' experiences related to
      patients having HF with ICDs making health-care decision at EOL: decision-making
      preferences, patients' perception on ICD deactivation, and communication methods.
      DISCUSSION: Health-care providers need to have knowledge of patients' decision
      making preferences. Preferences for decision-making include the allowing of
      appropriate people to involve and encourages direct conversation with family
      members even when advance directives is completed. Information of ICD function
      and the option of deactivation need to be clearly delivered to patients and
      family members. Education and guidelines will facilitate the communication of the
      preferences of EOL care.

PMID- 27034437
TI  - Applying Organizational Learning Research to Accountable Care Organizations.
AB  - To accomplish the goal of improving quality of care while simultaneously reducing
      cost, Accountable Care Organizations (ACOs) need to find new and better ways of
      providing health care to populations of patients. This requires implementing best
      practices and improving collaboration across the multiple entities involved in
      care delivery, including patients. In this article, we discuss seven lessons from
      the organizational learning literature that can help ACOs overcome the inherent
      challenges of learning how to work together in radically new ways. The lessons
      involve setting expectations, creating a supportive culture, and structuring the
      improvement efforts. For example, with regard to setting expectations, framing
      the changes as learning experiences rather than as implementation projects
      encourages the teams to utilize helpful activities, such as dry runs and pilot
      tests. It is also important to create an organizational culture where employees
      feel safe pointing out improvement opportunities and experimenting with new ways
      of working. With regard to structure, stable, cross-functional teams provide a
      powerful building block for effective improvement efforts. The article concludes
      by outlining opportunities for future research on organizational learning in
      ACOs.

PMID- 27034438
TI  - An Institutional Perspective on Accountable Care Organizations.
AB  - We employ aspects of institutional theory to explore how Accountable Care
      Organizations (ACOs) can effectively manage the multiplicity of ideas and
      pressures within which they are embedded and consequently better serve patients
      and their communities. More specifically, we draw on the concept of institutional
      logics to highlight the importance of understanding the conflicting principles
      upon which ACOs were founded. Based on previous research conducted both inside
      and outside health care settings, we argue that ACOs can combine attention to
      these principles (or institutional logics) in different ways; the options fall on
      a continuum from (a) segregating the effects of multiple logics from each other
      by compartmentalizing responses to multiple logics to (b) fully hybridizing the
      different logics. We suggest that the most productive path for ACOs is to situate
      their approach between the two extremes of "segregating" and "fully hybridizing."
      This strategic approach allows ACOs to develop effective responses that combine
      logics without fully integrating them. We identify three ways that ACOs can
      embrace institutional complexity short of fully hybridizing disparate logics: (1)
      reinterpreting practices to make them compatible with other logics; (2) engaging
      in strategies that take advantage of existing synergy between conflicting logics;
      (3) creating opportunities for people at frontline to develop innovative ways of
      working that combine multiple logics.

PMID- 27034439
TI  - Teaching Hospitals and the Disconnect Between Technology Adoption and Comparative
      Effectiveness Research: The Case of the Surgical Robot.
AB  - The surgical robot, a costly technology for treatment of prostate cancer with
      equivocal marginal benefit, rapidly diffused into clinical practice. We sought to
      evaluate the role of teaching in the early adoption phase of the surgical robot.
      Teaching hospitals were the primary early adopters: data from the Healthcare Cost
      and Utilization Project showed that surgical robots were acquired by 45.5% of
      major teaching, 18.0% of minor teaching and 8.0% of non-teaching hospitals during
      the early adoption phase. However, teaching hospital faculty produced little
      comparative effectiveness research: By 2008, only 24 published studies compared
      robotic prostatectomy outcomes to those of conventional techniques. Just ten of
      these studies (41.7%) were more than minimally powered, and only six (25%)
      involved cross-institutional collaborations. In adopting the surgical robot,
      teaching hospitals fulfilled their mission to innovate, but failed to generate
      corresponding scientific evidence.

PMID- 27034440
TI  - NewAccess for depression and anxiety: adapting the UK Improving Access to
      Psychological Therapies Program across Australia.
AB  - OBJECTIVE: NewAccess is a Low Intensity Cognitive Behaviour Therapy (LiCBT) early
      intervention pilot, for mild to moderate depression and anxiety. In November 2015
      the Australian Government Review of Mental Health Programmes and Services
      specifically highlighted the program, stating, "Primary Health Networks
      will....be encouraged and supported to work towards better utilisation of low
      intensity 'coaching' services for people with lesser needs, building on
      evaluations of programmes such as the NewAccess model of care, and the Improving
      Access to Psychological Therapies model of stepped care implemented in the United
      Kingdom." NewAccess runs in three sites (Adelaide, Canberra and North Coast New
      South Wales) based on the successful UK Improving Access to Psychological
      Therapies (IAPT) model. NewAccess involves training in evidence-based
      interventions, regular clinical supervision and recording outcome measures every
      session. Key performance indicators include functional recovery,loss of
      diagnosis, return to employment and early intervention. CONCLUSIONS: Adaptation
      to Australia accommodated contextual issues such as geographical isolation and
      infrastructure of the healthcare system. Initial recovery rates and projected
      economic viability for NewAccess are very promising, supporting wider adoption of
      an IAPT model across Australia. In addition it has resulted in the emergence of a
      new Australian workforce in community mental health with the LiCBT 'Coach'.

PMID- 27034441
TI  - Are elite cricketers more prone to suicide? A psychological autopsy study of Test
      cricketer suicides.
AB  - OBJECTIVES: It has been hypothesised that the very nature of the game predisposes
      elite cricketers to higher rates of suicide. AIM: We aim to estimate the suicide
      rate of male Test cricketers and to determine the reasons for suicide. METHODS:
      The suicide rate in male Test cricketers was determined. A psychological autopsy
      was conducted using published biographical data. RESULTS: Twenty suicides amongst
      2794 male Test cricketers from 1877 to 2014 yielded a suicide rate of 715.4 per
      100,000 for that period. Health, financial and relationship issues were
      prominent; depression and alcohol misuse were common. CONCLUSIONS: Most suicides
      in Test cricketers occurred post-retirement in mid to late life with similar
      correlates to those found in the general male population. The idiosyncrasies of
      cricket are unlikely to contribute to suicide; however, the post-retirement
      welfare of Test cricketers should remain a focus of concern and the greater
      supports available to contemporary Test cricketers needs to extend beyond
      retirement.

PMID- 27034442
TI  - Public access defibrillation: improving accessibility and outcomes.
AB  - BACKGROUND: Worldwide, out-of-hospital cardiac arrest (OHCA) remains a serious
      problem. Public access defibrillation (PAD) has been shown to be effective in
      improving survival in OHCA with good neurological outcome. SOURCES OF DATA:
      Original articles, reviews and national/international guidelines. AREAS OF
      AGREEMENT: Limitations to how much we can improve ambulance response times mean
      that the public have an essential role to play in OHCA survival. Training of
      laypersons in the use of automated external defibrillators (AEDs) has been shown
      to improve outcomes. Placement of AEDs should be related to underlying population
      demographics. AREAS OF CONTROVERSY: Placements of AEDs face cost constraints. PAD
      programs also face challenges in the upkeep of AEDs. Concerns about legal
      liability for lay rescuers to act remain. GROWING POINTS: Systematic programs
      should be in place to train the public in PAD. All AEDs should be listed in
      national registries and available for usage in an emergency. AREAS TIMELY FOR
      DEVELOPING RESEARCH: 'Smart' technology is being developed to improve
      accessibility of AEDs.

PMID- 27034444
TI  - Thinking about Occupation-Response and Exposure-Response Relationships: Vehicle
      Mechanics, Chrysotile, and Mesothelioma.

PMID- 27034443
TI  - The use of adjustable gastric bands for management of severe and complex obesity.
AB  - BACKGROUND: Obesity levels in the UK have reached a sustained high and ~4% of the
      population would be candidates for bariatric surgery based upon current UK NICE
      guidelines, which has important implications for Clinical Commissioning Groups.
      SOURCES OF DATA: Summary data from Cochrane systematic reviews, randomized
      controlled trials (RCTs) and cohort studies. AREAS OF AGREEMENT: Currently, the
      only treatment that offers significant and durable weight loss for those with
      severe and complex obesity is surgery. Three operations account for 95% of all
      bariatric surgery in the UK, but the NHS offers surgery to only a small fraction
      of those who could benefit. Laparoscopic adjustable gastric banding (gastric
      banding) has potentially the lowest risk and up-front costs of the three
      procedures. AREAS OF CONTROVERSY: Reliable Level 1 evidence of the relative
      effectiveness of the operations is lacking. GROWING POINTS: As a point
      intervention, weight loss surgery together with the chronic disease management
      strategy for obesity can prevent significant future disease and mortality, and
      the NHS should embrace both. AREAS TIMELY FOR DEVELOPING RESEARCH: Better RCT
      evidence is needed including clinical effectiveness and economic analysis to
      answer the important question 'which is the best of the three operations most
      frequently performed?' This review considers the current evidence for gastric
      banding for the treatment of severe and complex obesity.

PMID- 27034445
TI  - Landscape and Local Correlates of Bee Abundance and Species Richness in Urban
      Gardens.
AB  - Urban gardens may preserve biodiversity as urban population densities increase,
      but this strongly depends on the characteristics of the gardens and the
      landscapes in which they are embedded. We investigated whether local and
      landscape characteristics are important correlates of bee (Hymenoptera:
      Apiformes) abundance and species richness in urban community gardens. We worked
      in 19 gardens in the California central coast and sampled bees with aerial nets
      and pan traps. We measured local characteristics (i.e., vegetation and ground
      cover) and used the USGS National Land Cover Database to classify the landscape
      surrounding our garden study sites at 2 km scales. We classified bees according
      to nesting type (i.e., cavity, ground) and body size and determined which local
      and landscape characteristics correlate with bee community characteristics. We
      found 55 bee species. One landscape and several local factors correlated with
      differences in bee abundance and richness for all bees, cavity-nesting bees,
      ground-nesting bees, and different sized bees. Generally, bees were more abundant
      and species rich in bigger gardens, in gardens with higher floral abundance, less
      mulch cover, more bare ground, and with more grass. Medium bees were less
      abundant in sites surrounded by more medium intensity developed land within 2 km.
      The fact that local factors were generally more important drivers of bee
      abundance and richness indicates a potential for gardeners to promote bee
      conservation by altering local management practices. In particular, increasing
      floral abundance, decreasing use of mulch, and providing bare ground may promote
      bees in urban gardens.

PMID- 27034446
TI  - The Role of Multimodal Signals in Species Recognition Between Tree-Killing Bark
      Beetles in a Narrow Sympatric Zone.
AB  - When related species coexist, selection pressure should favor evolution of
      species recognition mechanisms to prevent interspecific pairing and wasteful
      reproductive encounters. We investigated the potential role of pheromone and
      acoustic signals in species recognition between two species of tree-killing bark
      beetles, the southern pine beetle,Dendroctonus frontalisZimmermann, and the
      western pine beetle,Dendroctonus brevicomisLeConte, in a narrow zone of sympatry,
      using reciprocal pairing experiments. Given the choice of adjacent con- or
      heterospecific female gallery entrance in a log, at least 85% of walking males
      chose the entrance of the conspecific, and half the males that initially entered
      heterospecific galleries re-emerged and entered the conspecific gallery within 15
      min. Waveform analysis of female acoustic "chirps" indicated interspecific
      differences in chirp timing. Males may use information from female acoustic
      signals to decide whether to enter or remain in the gallery. Individuals in
      forced heterospecific pairings (produced by confinement of a heterospecific male
      within the female entrance) did not differ in pheromone production from
      individuals of conspecific pairs. However, due to the absence of the right
      species of male, galleries with heterospecific pairs released an abnormal
      pheromone blend that lacked at least one key component of the aggregation
      pheromone of either species. The complete aggregation pheromone (i.e., the
      pheromone blend from entrances with pairs) does not appear to deter interspecific
      encounters or confer premating reproductive isolationper se; however, it may
      confer selective pressure for the maintenance of other reproductive isolation
      mechanisms.

PMID- 27034447
TI  - Natural Frequencies Do Not Foster Public Understanding of Medical Test Results.
AB  - Major organizations recommend presenting medical test results in terms of natural
      frequencies, rather than single-event probabilities. The evidence, however, is
      that natural frequency presentations benefit at most one-fifth of samples of
      health service users and patients. Only one study reported a substantial benefit
      of these presentations. Here, we replicate that study, testing online survey
      respondents. Study 1 attributed the previously reported benefit of natural
      frequencies to a scoring artifact. Study 2 showed that natural frequencies may
      elicit evaluations that conflict with the normatively correct one, potentially
      hindering informed decision making. Ironically, these evaluations occurred less
      often when respondents reasoned about single-event probabilities. These results
      suggest caution in promoting natural frequencies as the best way to communicate
      medical test data to health service users and patients.

PMID- 27034448
TI  - Cell cycle dependent cellular uptake of zinc oxide nanoparticles in human
      epidermal cells.
AB  - Metal oxide nanoparticles (NPs), including zinc oxide (ZnO) NPs have shown
      success for use as vehicles for drug delivery and targeting gene delivery in many
      diseases like cancer. Current anticancer chemotherapeutics fail to effectively
      differentiate between cancerous and normal cells. There is an urgent need to
      develop novel drug delivery system that can better target cancer cells while
      sparing normal cells and tissues. Particularly, ZnO NPs exhibit a high degree of
      cancer cell selectivity and induce cell death, oxidative stress, interference
      with the cell cycle progression and genotoxicity in cancerous cells. In this
      scenario, effective cellular uptake of NP seems to be crucial, which is shown to
      be affected by cell cycle progression. In the present study, the cytotoxic
      potential of ZnO NPs and the effect of different cell cycle phases on the uptake
      of ZnO NPs were examined in A431 cells. It is shown that the ZnO NPs led to cell
      death and reactive oxygen species generation and were able to induce cell cycle
      arrest in S and G2/M phase with the higher uptake in G2/M phase compared with
      other phases.

PMID- 27034449
TI  - Is there a need for non-drug treatments in headaches?

PMID- 27034450
TI  - Early referral for foot ulcers is vital, finds audit of diabetes care.

PMID- 27034451
TI  - Systematic review of symptom clusters in cardiovascular disease.
AB  - BACKGROUND: Although individual symptoms and symptom trajectories for various
      cardiovascular conditions have been reported, there is limited research
      identifying the symptom clusters that may provide a better understanding of
      patients' experiences with heart disease. AIMS: To summarize the state of the
      science in symptom cluster research for patients with acute coronary syndrome,
      myocardial infarction, coronary artery bypass surgery, and heart failure through
      systematic review and to provide direction for the translation of symptom cluster
      research into the clinical setting. METHODS: Databases were searched for articles
      from January 2000 through to May 2015 using MESH terms "symptoms, symptom
      clusters, acute coronary syndrome (ACS), myocardial infarction (MI), coronary
      heart disease (CHD), ischemic heart disease (IHD), heart failure (HF), coronary
      artery bypass surgery (CABS), cluster analyses, and latent classes." The search
      was limited to human studies, English language articles, and original articles
      investigating symptom clusters in individuals with heart disease. Fifteen studies
      meeting the criteria were included. RESULTS: For patients with ACS and MI,
      younger persons were more likely to experience clusters with the most symptoms.
      Older adults were more likely to experience clusters with the lowest number of
      symptoms and more diffuse and milder symptom clusters that are less reflective of
      classic ACS presentations. For HF patients, symptom clusters frequently included
      physical and emotional/cognitive components; edema clustered in only three
      studies. Symptom expression was congruent across geographical regions and
      cultures. CONCLUSIONS: The findings demonstrated similarities in symptom clusters
      during ACS, MI, and HF, despite multiple methods and analyses. These results may
      help clinicians to prepare at-risk patients for proper treatment-seeking and
      symptom self-management behaviors.

PMID- 27034452
TI  - Comparing the immunogenicity of the etanercept biosimilar SB4 with the innovator
      etanercept: another consideration.

PMID- 27034454
TI  - Access to specialist palliative care is still inadequate, audit finds.

PMID- 27034453
TI  - Increased prevalence and severity of radiographic hand osteoarthritis in patients
      with HIV-1 infection associated with metabolic syndrome: data from the cross
      sectional METAFIB-OA study.
AB  - OBJECTIVE: To determine radiographic hand osteoarthritis (HOA) prevalence in
      patients with HIV-1 infection in comparison with the general population and to
      address whether metabolic syndrome (MetS) may increase the risk of HOA during HIV
      1 infection. PATIENTS: Patients with HIV-1 infection and MetS (International
      Diabetes Federation, IDF criteria) aged 45-65 years were matched by age and
      gender to HIV-1-infected subjects without MetS and underwent hand radiographs.
      Framingham OA cohort was used as general population cohort. METHODS: Radiographic
      HOA was defined as Kellgren-Lawrence (KL) score >=2 on more than one joint.
      Radiographic severity was assessed by global KL score and number of OA joints.
      HOA prevalence was compared with that found in the Framingham study, stratified
      by age and sex. Logistic and linear regression models were used to determine the
      risk factors of HOA in patients with HIV-1 infection. RESULTS: 301 patients (88%
      male, mean age 53.4+/-5.0 years) were included, 152 with MetS and 149 without it.
      Overall, HOA prevalence was 55.5% and was higher for those with MetS than those
      without it (64.5% vs 46.3%, p=0.002). When considering men within each age group,
      HOA frequency was greater in patients with HIV-1 infection than the general
      population (all ages: 55.8% vs 38.7%; p<0.0001), due to the subgroup with MetS
      (64.9%; p<0.0001), as well as the subgroup without MetS, although not significant
      (46.6%; p=0.09). Risk of HOA was increased with MetS (OR 2.23, 95% 95% CI 1.26%
      to 3.96%) and age (OR 1.18, 95% CI 1.12 to 1.25). HOA severity was greater for
      patients with MetS than those without. HOA was not associated with previous or
      current exposure to protease inhibitors or HIV infection-related markers.
      CONCLUSIONS: HOA frequency is greater in patients with HIV-1 infection,
      especially those with MetS, than the general population. TRIAL REGISTRATION
      NUMBER: NCT02353767.

PMID- 27034455
TI  - The Diabetes Telephone Study: Design and challenges of a pragmatic cluster
      randomized trial to improve diabetic peripheral neuropathy treatment.
AB  - BACKGROUND: Challenges to effective pharmacologic management of symptomatic
      diabetic peripheral neuropathy include the limited effectiveness of available
      medicines, frequent side effects, and the need for ongoing symptom assessment and
      treatment titration for maximal effectiveness. We present here the rationale and
      implementation challenges of the Diabetes Telephone Study, a randomized trial
      designed to improve medication treatment, titration, and quality of life among
      patients with symptomatic diabetic peripheral neuropathy. METHODS: We implemented
      a pragmatic cluster randomized controlled trial to test the effectiveness of an
      automated interactive voice response tool designed to provide physicians with
      real-time patient-reported data about responses to newly prescribed diabetic
      peripheral neuropathy medicines. A total of 1834 primary care physicians treating
      patients in the diabetes registry at Kaiser Permanente Northern California were
      randomized into the intervention or control arm. In September 2014, we began
      identification and recruitment of patients assigned to physicians in the
      intervention group who receive three brief interactive calls every 2 months after
      a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms.
      These calls provide patients with the opportunity to report on symptoms, side
      effects, self-titration of medication dose and overall satisfaction with
      treatment. We plan to compare changes in self-reported quality of life between
      the intervention group and patients in the control group who receive three non
      interactive automated educational phone calls. RESULTS: Successful implementation
      of this clinical trial required robust stakeholder engagement to help tailor the
      intervention and to address pragmatic concerns such as provider time constraints.
      As of 27 October 2015, we had screened 2078 patients, 1447 of whom were eligible
      for participation. We consented and enrolled 1206 or 83% of those eligible. Among
      those enrolled, 53% are women and the mean age is 67 (standard deviation = 12)
      years. The racial ethnic make-up is 56% White, 8% Asian, 13% Black or African
      American, and 19% Hispanic or Latino. CONCLUSION: Innovative strategies are
      needed to guide improvements in healthcare delivery for patients with symptomatic
      diabetic peripheral neuropathy. This trial aims to assess whether real-time
      collection and clinical feedback of patient treatment experiences can reduce
      patient symptom burden. Implementation of a clinical trial closely involving
      clinical care required researchers to partner with clinicians. If successful,
      this intervention provides a critical information feedback loop that would
      optimize diabetic peripheral neuropathy medication titration through widely
      available interactive voice response technology.

PMID- 27034456
TI  - Introduction: Autoimmunity Special Issue.

PMID- 27034460
TI  - A radical prescription for the Medical Council of India.

PMID- 27034461
TI  - Editorial: Vgamma9Vdelta2 T cells: triple costimulation goes the distance.

PMID- 27034462
TI  - Editorial: Lung macrophages high on cannabinoids: jamming PAMs and taming TAMs?

PMID- 27034463
TI  - Offering women safer options than "vaginal seeding" for infants born by caesarean
      section.

PMID- 27034464
TI  - Angiopoietin-like 4 promotes intracellular degradation of lipoprotein lipase in
      adipocytes.
AB  - LPL hydrolyzes triglycerides in triglyceride-rich lipoproteins along the
      capillaries of heart, skeletal muscle, and adipose tissue. The activity of LPL is
      repressed by angiopoietin-like 4 (ANGPTL4) but the underlying mechanisms have not
      been fully elucidated. Our objective was to study the cellular location and
      mechanism for LPL inhibition by ANGPTL4. We performed studies in transfected
      cells, ex vivo studies, and in vivo studies with Angptl4(-/-) mice.
      Cotransfection of CHO pgsA-745 cells with ANGPTL4 and LPL reduced intracellular
      LPL protein levels, suggesting that ANGPTL4 promotes LPL degradation. This
      conclusion was supported by studies of primary adipocytes and adipose tissue
      explants from wild-type and Angptl4(-/-) mice. Absence of ANGPTL4 resulted in
      accumulation of the mature-glycosylated form of LPL and increased secretion of
      LPL. Blocking endoplasmic reticulum (ER)-Golgi transport abolished differences in
      LPL abundance between wild-type and Angptl4(-/-) adipocytes, suggesting that
      ANGPTL4 acts upon LPL after LPL processing in the ER. Finally, physiological
      changes in adipose tissue ANGPTL4 expression during fasting and cold resulted in
      inverse changes in the amount of mature-glycosylated LPL in wild-type mice, but
      not Angptl4(-/-) mice. We conclude that ANGPTL4 promotes loss of intracellular
      LPL by stimulating LPL degradation after LPL processing in the ER.

PMID- 27034465
TI  - Insertion of oxidized nucleotide triggers rapid DNA polymerase opening.
AB  - A novel mechanism is unveiled to explain why a pro-mutagenic nucleotide lesion
      (oxidized guanine, 8-oxoG) causes the mammalian DNA repair polymerase-beta (pol
      beta) to rapidly transition to an inactive open conformation. The mechanism
      involves unexpected features revealed recently in time-lapse crystallography.
      Specifically, a delicate water network associated with a lesion-stabilizing
      auxilliary product ion Mg(p) triggers a cascade of events that leads to poor
      active site geometry and the rupture of crucial molecular interactions between
      key residues in both the anti(8-oxoG:C) and syn(8-oxoG:A) systems. Once the base
      pairs in these lesioned systems are broken, dislocation of both Asp192 (a metal
      coordinating ligand) and the oxoG phosphate group (PO4) interfere with the
      hydrogen bonding between Asp192 and Arg258, whose rotation toward Asp192 is
      crucial to the closed-to-open enzyme transition. Energetically, the lesioned open
      states are similar in energy to those of the corresponding closed complexes after
      chemistry, in marked contrast to the unlesioned pol-beta anti(G:C) system, whose
      open state is energetically higher than the closed state. The delicate
      surveillance system offers a fundamental protective mechanism in the cell that
      triggers DNA repair events which help deter insertion of oxidized lesions.

PMID- 27034466
TI  - Genome-wide analysis of Musashi-2 targets reveals novel functions in governing
      epithelial cell migration.
AB  - The Musashi-2 (Msi2) RNA-binding protein maintains stem cell self-renewal and
      promotes oncogenesis by enhancing cell proliferation in hematopoietic and
      gastrointestinal tissues. However, it is unclear how Msi2 recognizes and
      regulates mRNA targets in vivo and whether Msi2 primarily controls cell growth in
      all cell types. Here we identified Msi2 targets with HITS-CLIP and revealed that
      Msi2 primarily recognizes mRNA 3'UTRs at sites enriched in multiple copies of UAG
      motifs in epithelial progenitor cells. RNA-seq and ribosome profiling
      demonstrated that Msi2 promotes targeted mRNA decay without affecting translation
      efficiency. Unexpectedly, the most prominent Msi2 targets identified are key
      regulators that govern cell motility with a high enrichment in focal adhesion and
      extracellular matrix-receptor interaction, in addition to regulators of cell
      growth and survival. Loss of Msi2 stimulates epithelial cell migration, increases
      the number of focal adhesions and also compromises cell growth. These findings
      provide new insights into the molecular mechanisms of Msi2's recognition and
      repression of targets and uncover a key function of Msi2 in restricting
      epithelial cell migration.

PMID- 27034467
TI  - The PIN domain endonuclease Utp24 cleaves pre-ribosomal RNA at two coupled sites
      in yeast and humans.
AB  - During ribosomal RNA (rRNA) maturation, cleavages at defined sites separate the
      mature rRNAs from spacer regions, but the identities of several enzymes required
      for 18S rRNA release remain unknown. PilT N-terminus (PIN) domain proteins are
      frequently endonucleases and the PIN domain protein Utp24 is essential for early
      cleavages at three pre-rRNA sites in yeast (A0, A1 and A2) and humans (A0, 1 and
      2a). In yeast, A1 is cleaved prior to A2 and both cleavages require base-pairing
      by the U3 snoRNA to the central pseudoknot elements of the 18S rRNA. We found
      that yeast Utp24 UV-crosslinked in vivo to U3 and the pseudoknot, placing Utp24
      close to cleavage at site A1. Yeast and human Utp24 proteins exhibited in vitro
      endonuclease activity on an RNA substrate containing yeast site A2. Moreover, an
      intact PIN domain in human UTP24 was required for accurate cleavages at sites 1
      and 2a in vivo, whereas mutation of another potential site 2a endonuclease, RCL1,
      did not affect 18S production. We propose that Utp24 cleaves sites A1/1 and A2/2a
      in yeast and human cells. 

PMID- 27034468
TI  - Structure and mechanism of error-free replication past the major benzo[a]pyrene
      adduct by human DNA polymerase kappa.
AB  - Benzo[a]pyrene (BP) is a well-known and frequently encountered carcinogen which
      generates a bulky DNA adduct (+)-trans-10S-BP-N(2)-dG (BP-dG) in cells. DNA
      polymerase kappa (polkappa) is the only known Y-family polymerase that bypasses
      BP-dG accurately and thus protects cells from genotoxic BP. Here, we report the
      structures of human polkappa in complex with DNA containing either a normal
      guanine (G) base or a BP-dG adduct at the active site and a correct
      deoxycytidine. The structures and supporting biochemical data reveal a unique
      mechanism for accurate replication by translesion synthesis past the major bulky
      adduct. The active site of polkappa opens at the minor groove side of the DNA
      substrate to accommodate the bulky BP-dG that is attached there. More
      importantly, polkappa stabilizes the lesion DNA substrate in the same active
      conformation as for regular B-form DNA substrates and the bulky BPDE ring in a 5'
      end pointing conformation. The BP-dG adducted DNA substrate maintains a Watson
      Crick (BP-dG:dC) base pair within the active site, governing correct nucleotide
      insertion opposite the bulky adduct. In addition, polkappa's unique N-clasp
      domain supports the open conformation of the enzyme and the extended conformation
      of the single-stranded template to allow bypass of the bulky lesion. This work
      illustrates the first molecular mechanism for how a bulky major adduct is
      replicated accurately without strand misalignment and mis-insertion.

PMID- 27034470
TI  - How do we define when we die?

PMID- 27034469
TI  - Two p53 tetramers bind one consensus DNA response element.
AB  - p53 tumor suppressor is a transcription factor that controls cell cycle and
      genetic integrity. In response to genotoxic stress p53 activates DNA repair, cell
      cycle arrest, apoptosis or senescence, which are initiated via p53 binding to its
      specific DNA response elements (RE). The consensus p53 DNA RE consists of two
      decameric palindromic half-site sequences. Crystallographic studies have
      demonstrated that two isolated p53 DNA-binding core domains interact with one
      half-site of the p53 DNA REs suggesting that one p53 tetramer is bound to one RE.
      However, our recent 3D cryo-EM studies showed that the full-length p53 tetramer
      is bound to only one half-site of RE.Here, we have used biochemical and electron
      microscopy (EM) methods to analyze DNA-binding of human and murine p53 tetramers
      to various p53 DNA REs. Our new results demonstrate that two p53 tetramers can
      interact sequence-specifically with one DNA RE at the same time. In particular,
      the EM structural analysis revealed that two p53 tetramers bind one DNA RE
      simultaneously with DNA positioned between them. These results demonstrate a mode
      different from that assumed previously for the p53-DNA interaction and suggest
      important biological implications on p53 activity as a transcriptional regulator
      of cellular response to stress.

PMID- 27034471
TI  - Relationship Between Low Relative Muscle Mass and Coronary Artery Calcification
      in Healthy Adults.
AB  - OBJECTIVE: Sarcopenia or low muscle mass is related to cardiovascular risk
      factors; however, the association between low muscle mass and subclinical
      atherosclerosis has been largely unexplored. We investigated whether muscle mass
      is related to coronary artery calcification (CAC) in a large sample of middle
      aged asymptomatic adults. APPROACH AND RESULTS: We performed a cross-sectional
      study of 31 108 asymptomatic adults without cancer, diabetes mellitus, or known
      cardiovascular disease who underwent a health checkup examination including
      cardiac tomography estimation of CAC scores between 2012 and 2013. Skeletal
      muscle mass index (SMI) [SMI (%)=total skeletal muscle mass (kg)/body weight
      (kg)*100] was estimated using a bioelectrical impedance analyzer. We assessed the
      relationship between SMI and CAC scores using both multivariate-adjusted Tobit
      models and multinomial logistic regression models. Of the 31 108 subjects, 3374
      subjects (10.9%) had a CAC score 1 to 100, and 628 subjects (2.0%) had a CAC
      score >100. SMI was inversely associated with CAC score ratios. Specifically, in
      a multivariable-adjusted model adjusting for potential confounders, CAC score
      ratios (95% confidence intervals) of SMI for quartiles 1, 2, and 3 compared with
      quartile 4 were 2.27 (1.70-3.05), 1.46 (1.15-1.85), and 1.24 (0.98-1.55),
      respectively (P for trend <0.001). Adjusting for insulin resistance reduced the
      magnitude of the associations, but they remained statistically significant.
      CONCLUSIONS: Relative muscle mass was negatively associated with the prevalence
      of coronary calcification, supporting low muscle mass as an independent risk
      factor of coronary heart disease.

PMID- 27034472
TI  - Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular
      Disease: The Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: Vitamin K-dependent proteins (VKDPs), which require post-translational
      modification to achieve biological activity, seem to contribute to thrombus
      formation, vascular calcification, and vessel stiffness. Whether VKDP activity is
      prospectively associated with incident cardiovascular disease has not been
      studied. APPROACH AND RESULTS: VKDP activity was determined by measuring
      circulating des-gamma-carboxy prothrombin concentrations in a random sample of
      709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic
      Study of Atherosclerosis (MESA). Lower des-gamma-carboxy prothrombin
      concentrations reflect greater VKDP activity. Subjects were followed up for the
      risk of ischemic cardiovascular disease (coronary heart disease, stroke, and
      fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first
      ischemic CVD events occurred during follow-up. The incidence of ischemic
      cardiovascular disease increased progressively across des-gamma-carboxy
      prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in
      the lowest and highest quartiles. In analyses adjusted for traditional
      cardiovascular risk factors and measures of vitamin K intake, a doubling of des
      gamma-carboxy prothrombin concentration was associated with a 1.53 (95%
      confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic
      cardiovascular disease. The association was consistent across strata of
      participants with diabetes mellitus, hypertension, renal impairment, and low
      vitamin K nutritional intake. CONCLUSIONS: In this sample of middle-aged and
      older adults, VKDP activity was associated with incident ischemic cardiovascular
      events. Further studies to understand the role of this large class of proteins in
      cardiovascular disease are warranted.

PMID- 27034473
TI  - Loss of Biglycan Enhances Thrombin Generation in Apolipoprotein E-Deficient Mice:
      Implications for Inflammation and Atherosclerosis.
AB  - OBJECTIVE: Thrombin signaling promotes atherosclerosis by initiating inflammatory
      events indirectly through platelet activation and directly via protease-activated
      receptors. Therefore, endogenous thrombin inhibitors may be relevant modulators
      of atheroprogression and cardiovascular risk. In addition, endogenous thrombin
      inhibitors may affect the response to non-vitamin K-dependent oral
      anticoagulants. Here, the question was addressed whether the small leucine-rich
      proteoglycan biglycan acts as an endogenous thrombin inhibitor in atherosclerosis
      through activation of heparin cofactor II. APPROACH AND RESULTS: Biglycan
      concentrations were elevated in the plasma of patients with acute coronary
      syndrome and in male Apolipoprotein E-deficient (ApoE(-/-)) mice. Biglycan was
      detected in the glycocalyx of capillaries and the subendothelial matrix of
      arterioles of ApoE(-/-) mice and in atherosclerotic plaques. Thereby a vascular
      compartment is provided that may mediate the endothelial and subendothelial
      activation of heparin cofactor II through biglycan. ApoE and Bgn double-deficient
      (ApoE(-/-)/Bgn(-/0)) mice showed higher activity of circulating thrombin,
      increased platelet activation and platelet adhesion in vivo, supporting a role of
      biglycan in balancing thrombin activity. Furthermore, concentrations of
      circulating cytokines and aortic macrophage content were elevated in ApoE(-/
      )/Bgn(-/0) mice, suggesting a proinflammatory phenotype. Elevated platelet
      activation and macrophage accumulation were reversed by treating ApoE(-/-)/Bgn(
      /0) mice with the thrombin inhibitor argatroban. Ultimately, ApoE(-/-)/Bgn(-/0)
      mice developed aggravated atherosclerosis. CONCLUSIONS: The present results
      indicate that biglycan plays a previously unappreciated protective role during
      the progression of atherosclerosis by inhibiting thrombin activity, platelet
      activation, and finally macrophage-mediated plaque inflammation.

PMID- 27034474
TI  - Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From
      Interstitial Fluid in Type 2 Diabetes Mellitus-Brief Report.
AB  - OBJECTIVE: Patients with type 2 diabetes mellitus (T2D) have an increased risk of
      cardiovascular disease, the mechanism of which is incompletely understood. Their
      high-density lipoprotein (HDL) particles in plasma have been reported to have
      impaired cholesterol efflux capacity. However, the efflux capacity of HDL from
      interstitial fluid (IF), the starting point for reverse cholesterol transport,
      has not been studied. We here investigated the cholesterol efflux capacity of HDL
      from IF and plasma from T2D patients and healthy controls. APPROACH AND RESULTS:
      HDL was isolated from IF and peripheral plasma from 35 T2D patients and 35 age-
      and sex-matched healthy controls. Cholesterol efflux to HDL was determined in
      vitro, normalized for HDL cholesterol, using cholesterol-loaded macrophages.
      Efflux capacity of plasma HDL was 10% lower in T2D patients than in healthy
      controls, in line with previous observations. This difference was much more
      pronounced for HDL from IF, where efflux capacity was reduced by 28% in T2D.
      Somewhat surprisingly, the efflux capacity of HDL from IF was lower than that of
      plasma HDL, by 15% and 32% in controls and T2D patients, respectively.
      CONCLUSION: These data demonstrate that (1) HDL from IF has a lower cholesterol
      efflux capacity than plasma HDL and (2) the efflux capacity of HDL from IF is
      severely impaired in T2D when compared with controls. Because IF comprises the
      compartment where reverse cholesterol transport is initiated, the marked
      reduction in cholesterol efflux capacity of IF-HDL from T2D patients may play an
      important role for their increased risk to develop atherosclerosis.

PMID- 27034475
TI  - Advances in clinical determinants and neurological manifestations of B vitamin
      deficiency in adults.
AB  - B vitamin deficiency is a leading cause of neurological impairment and disability
      throughout the world. Multiple B vitamin deficiencies often coexist, and thus an
      understanding of the complex relationships between the different biochemical
      pathways regulated in the brain by these vitamins may facilitate prompter
      diagnosis and improved treatment. Particular populations at risk for multiple B
      vitamin deficiencies include the elderly, people with alcoholism, patients with
      heart failure, patients with recent obesity surgery, and vegetarians/vegans.
      Recently, new clinical settings that predispose individuals to B vitamin
      deficiency have been highlighted. Moreover, other data indicate a possible
      pathogenetic role of subclinical chronic B vitamin deficiency in
      neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and
      amyotrophic lateral sclerosis. In light of these findings, this review examines
      the clinical manifestations of B vitamin deficiency and the effect of B vitamin
      deficiency on the adult nervous system. The interrelationships of multiple B
      vitamin deficiencies are emphasized, along with the clinical phenotypes related
      to B vitamin deficiencies. Recent advances in the clinical determinants and
      diagnostic clues of B vitamin deficiency, as well as the suggested therapies for
      B vitamin disorders, are described. 

PMID- 27034476
TI  - Complete Genome Sequences of Two Hydrangea Ringspot Virus Isolates from Japan.
AB  - Hydrangea ringspot virus (HdRSV) is a plant RNA virus, naturally
      infectingHydrangea macrophylla Here, we report the first genomic sequences of two
      HdRSV isolates from hydrangea plants in Japan. The overall nucleotide sequences
      of these Japanese isolates were 96.0 to 96.3% identical to those of known
      European isolates. 

PMID- 27034477
TI  - Genome Sequence of Arthrobacter antarcticus Strain W2, Isolated from a
      Slaughterhouse.
AB  - We report the draft genome sequence ofArthrobacter antarcticusstrain W2, which
      was isolated from a wall of a small slaughterhouse in Denmark. The 4.43-Mb genome
      sequence was assembled into 170 contigs. 

PMID- 27034478
TI  - Genome Sequence of Kocuria palustris Strain W4.
AB  - We report the 3.09 Mb draft genome sequence ofKocuria palustrisW4, isolated from
      a slaughterhouse in Denmark. 

PMID- 27034479
TI  - Draft Genome Sequences of Two Kocuria Isolates, K. salsicia G1 and K. rhizophila
      G2, Isolated from a Slaughterhouse in Denmark.
AB  - We report here the draft genome sequences ofKocuria salsiciaG1 andKocuria
      rhizophilaG2, which were isolated from a meat chopper at a small slaughterhouse
      in Denmark. The two annotated genomes are 2.99 Mb and 2.88 Mb in size,
      respectively. 

PMID- 27034480
TI  - Genome Sequence of Kocuria varians G6 Isolated from a Slaughterhouse in Denmark.
AB  - We report here the first draft genome sequence ofKocuria variansG6, which was
      isolated from a meat chopper at a small slaughterhouse in Denmark. The 2.90-Mb
      genome sequence consists of 95 contigs and contains 2,518 predicted protein
      coding genes. 

PMID- 27034481
TI  - Draft Genome Assembly of Two Pseudoclavibacter helvolus Strains, G8 and W3,
      Isolated from Slaughterhouse Environments.
AB  - We report the draft genome sequences of twoPseudoclavibacter helvolusstrains.
      Strain G8 was isolated from a meat chopper and strain W3 isolated from the wall
      of a small slaughterhouse in Denmark. The two annotated genomes are 3.91 Mb and
      4.00 Mb in size, respectively. 

PMID- 27034482
TI  - Draft Genome Sequences of Seven Multidrug-Resistant Acinetobacter baumannii
      Strains, Isolated from Respiratory Samples in Spain.
AB  - The draft genome sequences of seven multidrug-resistantAcinetobacter
      baumanniiclinical strains belonging to sequence types ST-208 and ST-218 are
      reported in this study. They were isolated from tracheobronchial aspirate of
      mechanically ventilated adult patients admitted to the intensive care unit of a
      Spanish tertiary hospital during 2010 to 2011. 

PMID- 27034483
TI  - Complete Genome Sequence of a Human Cytomegalovirus Strain AD169 Bacterial
      Artificial Chromosome Clone.
AB  - The complete sequence of the human cytomegalovirus strain AD169 (variant ATCC)
      cloned as a bacterial artificial chromosome (AD169-BAC, also known as HB15 or
      pHB15) was determined. The viral genome has a length of 230,290 bp and shows 52
      nucleotide differences compared to a previously sequenced AD169varATCC clone. 

PMID- 27034484
TI  - Complete Genome Sequence of a Genotype G23P[37] Pheasant Rotavirus Strain
      Identified in Hungary.
AB  - We investigated the genomic properties of a rotavirus A strain isolated from
      diarrheic pheasant poults in Hungary in 2015. Sequence analyses revealed a shared
      genomic constellation (G23-P[37]-I4-R4-C4-M4-A16-N10-T4-E4-H4) and close
      relationship (range of nucleotide sequence similarity: VP2, 88%; VP1 and NSP4,
      98%) with another pheasant rotavirus strain isolated previously in Germany. 

PMID- 27034485
TI  - Complete Genome Sequence of Porcine Circovirus Strain YiY-3-2-H5 with a Novel
      Insertion, Isolated from Hunan Province, China.
AB  - The complete genome of porcine circovirus type 2 (PCV2) strain YiY-3-2-H5
      contains a cytidine insertion at position 962 in open reading frame 1. This
      insertion causes a reading frameshift of the rep gene, and thereafter a premature
      stop codon is present at the 3' terminal end of this gene. 

PMID- 27034486
TI  - Draft Genome Sequence of Corynebacterium ulcerans Strain 04-3911, Isolated from
      Humans.
AB  - Corynebacterium ulceransis a pathogenic bacterium infecting wild and domesticated
      animals; some infection cases in humans have increased throughout the world. The
      current study describes the draft genome of strain 04-3911, isolated from humans.
      The draft genome has 2,492,680 bp, 2,143 coding sequences, 12 rRNA genes, and 50
      tRNA genes. 

PMID- 27034487
TI  - Draft Genome Sequence of Toxigenic Corynebacterium ulcerans Strain 04-7514,
      Isolated from a Dog in France.
AB  - Here, we present the draft genome of toxigenicCorynebacterium ulceransstrain 04
      7514. The draft genome has 2,497,845 bp, 2,059 coding sequences, 12 rRNA genes,
      46 tRNA genes, 150 pseudogenes, 1 clustered regularly interspaced short
      palindromic repeat (CRISPR) array, and a G+C content of 53.50%. 

PMID- 27034488
TI  - Draft Genome Sequence of Leuconostoc mesenteroides 213M0, Isolated from
      Traditional Fermented Mare Milk Airag in Bulgan Aimag, Mongolia.
AB  - Leuconostoc mesenteroides213M0 was isolated from traditional fermented mare milk
      airag in Bulgan Aimag, Mongolia. This strain produces a listericidal bacteriocin
      like inhibitory substance. Here, we report the draft genome sequence of this
      organism. 

PMID- 27034489
TI  - Genome Sequences of Five Nonvirulent Listeria monocytogenes Serovar 4 Strains.
AB  - We present the complete genome sequences of five nonpathogenicListeria
      monocytogenesserovar 4 strains: WSLC 1018 (4e), 1019 (4c), 1020 (4a), 1033 (4d),
      and 1047 (4d). These sequences may help to uncover genes involved in the
      synthesis of the serovar antigens-phenotypic determinants of virulence deemed
      clinically relevant. 

PMID- 27034490
TI  - Draft Genome Sequence of Flavobacterium sp. 316, a Baltic Sea Isolate Exhibiting
      a High Level of Resistance to Marine Stress Conditions.
AB  - Here, we present the draft genome sequence ofFlavobacteriumsp. 316, isolated from
      brackish water of the Gulf of Gdansk, southern Baltic Sea. The assembly contains
      3,971,755 bp in 17 scaffolds. The sequence will facilitate postgenomic studies on
      bacterial stress responses in the challenging habitat of the Baltic Sea. 

PMID- 27034491
TI  - Draft Genome Sequences of Streptococcus pneumoniae with High-Level Resistance to
      Respiratory Fluoroquinolones.
AB  - Streptococcus pneumoniaeis the leading cause of community-acquired pneumonia.
      Levofloxacin is a fluoroquinolone used for treatment of severe community-acquired
      pneumonia. Here, we describe the draft genome sequences ofS. pneumoniaewith
      emerging resistance to levofloxacin, resulting in failure of treatment of
      pneumococcal pneumonia. 

PMID- 27034492
TI  - Complete Genome Sequence of Mycobacterium bovis Strain BCG-1 (Russia).
AB  - Mycobacterium bovisBCG (Bacille Calmette-Guerin) is a vaccine strain used for
      protection against tuberculosis. Here, we announce the complete genome sequence
      ofM. bovisstrain BCG-1 (Russia). Extensive use of this strain necessitates the
      study of its genome stability by comparative analysis. 

PMID- 27034493
TI  - Draft Genome Sequence of Two Sphingopyxis sp. Strains, Dominant Members of the
      Bacterial Community Associated with a Drinking Water Distribution System
      Simulator.
AB  - We report the draft genomes of twoSphingopyxissp. strains isolated from a
      chloraminated drinking water distribution system simulator. Both strains are
      ubiquitous residents and early colonizers of water distribution systems. Genomic
      annotation identified a class 1 integron (intI1) gene associated with sulfonamide
      (sul1) and puromycin (pac) antibiotic resistance genes. 

PMID- 27034494
TI  - Draft Genome Sequence of the Dimorphic Fungus Sporothrix pallida, a Nonpathogenic
      Species Belonging to Sporothrix, a Genus Containing Agents of Human and Feline
      Sporotrichosis.
AB  - Sporothrix pallidais considered to be a mostly avirulent environmental fungus,
      phylogenetically closely related to the well-known pathogenSporothrix schenckii
      Here, we present the first assembly of its genome, which provides a valuable
      resource for future comparative genomic studies between nonpathogenic and
      pathogenicSporothrixspp. 

PMID- 27034495
TI  - Complete Genome Sequence of Hepatitis B Virus Genotype E, the First Molecular
      Characterization from an Imported Case in Mexico.
AB  - Hepatitis B virus infection is currently a global public health problem. Here, we
      present the first characterization and complete genome sequence of a strain
      belonging to genotype E in Mexico, obtained from a foreign carrier with chronic
      infection. 

PMID- 27034496
TI  - Draft Genome Sequence of the N2-Fixing Cyanobacterium Nostoc piscinale CENA21,
      Isolated from the Brazilian Amazon Floodplain.
AB  - We announce here the draft genome sequence ofNostoc piscinaleCENA21, a
      diazotrophic heterocyst-forming cyanobacterium isolated from the Solimoes River,
      Amazon Basin, Brazil. It consists of one circular chromosome scaffold with 11
      contigs and total size of 7,094,556 bp. Secondary metabolite annotations indicate
      a good source for the discovery of novel natural products. 

PMID- 27034497
TI  - Draft Genome Sequence of Mycobacterium fortuitum Isolated from Murine Brain.
AB  - Mycobacterium fortuitumsubsp.fortuitumATCC 6841 is a type and standard laboratory
      testing quality control strain. We report here the completed draft genome
      sequence for a strain isolated from the brains ofM. fortuitum-infected mice. 

PMID- 27034498
TI  - Whole-Genome Sequencing of Two Latin American-Mediterranean Extensively Drug
      Resistant Mycobacterium tuberculosis Clinical Isolates from Medellin, Colombia.
AB  - Colombia, with a tuberculosis incidence of 33 cases per 100,000 population, is
      one of the countries that have reported extensively drug-resistant Mycobacterium
      tuberculosis (XDR-TB). We report the high-quality draft genome sequences of two
      Latin American-Mediterranean XDR-TB clinical isolates (TBR-152 and TBR-175),
      comprising 4,303,775 bp and 4,330,115 bp, respectively. 

PMID- 27034499
TI  - Complete Genome Sequence of Streptococcus pneumoniae Serotype 19A, a Blood
      Clinical Isolate from Northeast Mexico.
AB  - We report here the draft genome sequence of aStreptococcus pneumoniaestrain
      isolated in Monterrey, Mexico, MTY1662SN214, from a man with purpura fulminans.
      The strain belongs to the invasive and multidrug-resistant serogroup 19A,
      sequence type 320 (ST320). The draft genome sequence consists of 60 large
      contigs, a total of 2,069,474 bp, and has a G+C content of 39.7%. 

PMID- 27034500
TI  - Draft Genome Sequences of Methanoculleus horonobensis Strain JCM 15517,
      Methanoculleus thermophilus Strain DSM 2373, and Methanofollis ethanolicus Strain
      JCM 15103, Hydrogenotrophic Methanogens Belonging to the Family
      Methanomicrobiaceae.
AB  - The familyMethanomicrobiaceaecomprises hydrogen- and formate-utilizing
      methanogens. Genome sequencing of nine species ofMethanomicrobiaceaehas been
      conducted so far. Here, we report three additional draft genome sequences
      ofMethanomicrobiaceae, those ofMethanoculleus horonobensisJCM 15517
      (=T10(T)),Methanoculleus thermophilusDSM 2373 (=CR-1(T)), andMethanofollis
      ethanolicusJCM 15103 (=HASU(T)). 

PMID- 27034501
TI  - Draft Genome Sequence of Paenibacillus sp. Strain DMB5, Acclimatized and Enriched
      for Catabolizing Anthropogenic Compounds.
AB  - Here, we present the draft genome sequence ofPaenibacillussp. strain DMB5,
      isolated from polluted sediments of the Kharicut Canal, Vatva, India, having a
      genome size of 7.5 Mbp and 7,077 coding sequences. The genome of this dye
      degrading bacterium provides valuable information on the microbe-mediated
      biodegradation of anthropogenic compounds. 

PMID- 27034502
TI  - Draft Genome Sequence of Vibrio toranzoniae Strain CECT 7225T.
AB  - Vibrio toranzoniae(CECT 7225(T)) was isolated from healthy reared carpet shell
      clams in Galicia (Northwest Spain). In addition, this species has been recently
      identified as a potential pathogen of red conger eel in Chile. The draft genome
      sequence has 4.5 Mbp, a G+C content of 43.9%, and >3,800 protein-coding genes. 

PMID- 27034503
TI  - Draft Genome Sequence of Paenibacillus amylolyticus Heshi-A3, Isolated from
      Fermented Rice Bran in a Japanese Fermented Seafood Dish.
AB  - Paenibacillus amylolyticusstrain Heshi-A3 was isolated in Fukui prefecture,
      Japan, from fermented rice bran in Heshiko, a traditional dish that is produced
      by aging salted mackerel with fresh rice bran at an ambient temperature for
      around 7 months to over one year. Here, we report the draft genome sequence
      ofPaenibacillus amylolyticusstrain Heshi-A3. 

PMID- 27034504
TI  - Complete Genome Sequence of the Engineered Escherichia coli SHuffle Strains and
      Their Wild-Type Parents.
AB  - SHuffle strains are genetically engineeredEscherichia colistrains that are
      capable of oxidizing cysteines within proteins to form disulfide bonds. Here we
      present the complete genome of both the K-12 and B versions of SHuffle strains
      along with their parental ancestors. These strains have been of significant use
      to both the general scientific community and the biotech industry, interested in
      producing novel disulfide-bonded proteins that were hitherto unable to be
      expressed in standardE. coliexpression strains. 

PMID- 27034505
TI  - An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor
      function in a mouse model.
AB  - A nonsynonymous single-nucleotide polymorphism at codon 47 in TP53 exists in
      African-descent populations (P47S, rs1800371; referred to here as S47). Here we
      report that, in human cell lines and a mouse model, the S47 variant exhibits a
      modest decrease in apoptosis in response to most genotoxic stresses compared with
      wild-type p53 but exhibits a significant defect in cell death induced by
      cisplatin. We show that, compared with wild-type p53, S47 has nearly
      indistinguishable transcriptional function but shows impaired ability to
      transactivate a subset of p53 target genes, including two involved in
      metabolism:Gls2(glutaminase 2) and Sco2 We also show that human and mouse cells
      expressing the S47 variant are markedly resistant to cell death by agents that
      induce ferroptosis (iron-mediated nonapoptotic cell death). We show that mice
      expressing S47 in homozygous or heterozygous form are susceptible to spontaneous
      cancers of diverse histological types. Our data suggest that the S47 variant may
      contribute to increased cancer risk in individuals of African descent, and our
      findings highlight the need to assess the contribution of this variant to cancer
      risk in these populations. These data also confirm the potential relevance of
      metabolism and ferroptosis to tumor suppression by p53.

PMID- 27034507
TI  - 17alpha-Estradiol: A Novel Therapeutic Intervention to Target Age-related Chronic
      Inflammation.

PMID- 27034506
TI  - Sperm is epigenetically programmed to regulate gene transcription in embryos.
AB  - For a long time, it has been assumed that the only role of sperm at fertilization
      is to introduce the male genome into the egg. Recently, ideas have emerged that
      the epigenetic state of the sperm nucleus could influence transcription in the
      embryo. However, conflicting reports have challenged the existence of epigenetic
      marks on sperm genes, and there are no functional tests supporting the role of
      sperm epigenetic marking on embryonic gene expression. Here, we show that sperm
      is epigenetically programmed to regulate embryonic gene expression. By comparing
      the development of sperm- and spermatid-derived frog embryos, we show that the
      programming of sperm for successful development relates to its ability to
      regulate transcription of a set of developmentally important genes. During
      spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3
      marks. Experimental removal of these epigenetic marks at fertilization de
      regulates gene expression in the resulting embryos in a paternal chromatin
      dependent manner. This demonstrates that epigenetic instructions delivered by the
      sperm at fertilization are required for correct regulation of gene expression in
      the future embryos. The epigenetic mechanisms of developmental programming
      revealed here are likely to relate to the mechanisms involved in
      transgenerational transmission of acquired traits. Understanding how parental
      experience can influence development of the progeny has broad potential for
      improving human health.

PMID- 27034508
TI  - Trajectories of Unhealthy Behaviors in Midlife and Risk of Disability at Older
      Ages in the Whitehall II Cohort Study.
AB  - BACKGROUND: Most of the evidence on the association between unhealthy behaviors
      and disability comes from studies in the elderly, where reverse causation and
      selection bias may distort associations; thus, studies based on midlife
      trajectories of health behaviors are needed. We examined the association of
      trajectories of four health behaviors (physical activity, fruit and vegetable
      consumption, smoking, alcohol), starting in midlife and over 20 years, with
      subsequent disability risk in early old age (range = 54-84 years) in the
      Whitehall II cohort study. METHODS: Disability was assessed three times over 3
      years. A hierarchical disability indicator was constructed; participants were
      considered disabled if they reported difficulties with mobility and instrumental
      activities of daily living or with mobility and instrumental and basic activities
      of daily living. Behavior trajectories were defined using group-based trajectory
      models. Multivariable generalized estimating equations logistic models were used
      to examine their independent associations with disability. RESULTS: Of 6,825
      participants, 19.2% reported being disabled at least once. In mutually adjusted
      models, participants with persistent inactivity or declining physical activity,
      recent ex- or current smokers, and persistent/recent abstainers or persistent
      heavy drinkers had a higher disability risk, whereas fruit and vegetable
      consumption was not associated with disability. Disability risk increased
      progressively with the number of unhealthy behavior trajectories: the odds ratio
      of disability for 2-3 unhealthy trajectories was 2.69 (95% confidence interval =
      2.26-3.19); these associations remained after adjustment for a wide range of
      covariates. CONCLUSIONS: Unhealthy behavior trajectories in midlife are
      associated with greater disability risk later in life.

PMID- 27034509
TI  - Genetic diversity and population structure of Polistes nimpha based on DNA
      microsatellite markers.
AB  - The Eurasiatic Polistes nimpha belongs to primitively eusocial wasps for which no
      data are available on its population's genetic structure and
      relatedness/relationships of individuals. The purpose of this research is to
      determine the amplification efficiency in P. nimpha of microsatellite primers
      developed for P. dominula and using these primers, to explore genetic diversity,
      population structure and relatedness/relationship of P. nimpha in the context of
      its reproductive options. Eight out of twelve microsatellite markers analyzed on
      59 individuals (pupae and larvae) were polymorphic (mean PIC = 0.545) and mutated
      following the stepwise mutation model. The Bayesian clustering method gave the
      probability of >0.898 of there being 10 clusters within the pooled sample of 15
      nests. In two or three nest clusters, full- and/or half-siblings and unrelated
      individuals occurred. A significant correlation between genetic and geographic
      distances was detected. There are three main possibilities that come into play to
      explain our genetic results and direct field observations: cooperative nest
      foundation, visitations, and/or usurpation events. So far there is no conclusive
      evidence to exclude or support any of these possibilities.

PMID- 27034510
TI  - Bayesian Group Sequential Clinical Trial Design using Total Toxicity Burden and
      Progression-Free Survival.
AB  - Delivering radiation to eradicate a solid tumor while minimizing damage to nearby
      critical organs remains a challenge. For esophageal cancer, radiation therapy may
      damage the heart or lungs, and several qualitatively different, possibly
      recurrent toxicities associated with chemoradiation or surgery may occur, each at
      two or more possible grades. In this article, we describe a Bayesian group
      sequential clinical trial design, based on total toxicity burden (TTB) and
      progression-free survival duration, for comparing two radiation therapy
      modalities for esophageal cancer. Each patient's toxicities are modeled as a
      multivariate doubly stochastic Poisson point process, with marks identifying
      toxicity grades. Each grade of each type of toxicity is assigned a severity
      weight, elicited from clinical oncologists familiar with the disease and
      treatments. TTB is defined as a severity-weighted sum over the different
      toxicities that may occur up to 12 months from the start of treatment. Latent
      frailties are used to formulate a multivariate model for all outcomes. Group
      sequential decision rules are based on posterior mean TTB and progression-free
      survival time. The proposed design is shown to provide both larger power and
      smaller mean sample size when compared to a conventional bivariate group
      sequential design.

PMID- 27034512
TI  - Best practices for sharing information through data platforms: establishing the
      principles.

PMID- 27034513
TI  - Knowledge sharing during public health emergencies: from global call to effective
      implementation.

PMID- 27034514
TI  - Public health round-up.

PMID- 27034515
TI  - Putting taxes into the diet equation.

PMID- 27034516
TI  - The mysteries of type 2 diabetes in developing countries.

PMID- 27034517
TI  - Sexual and reproductive health and human rights of women living with HIV: a
      global community survey.
AB  - OBJECTIVE: To determine the sexual and reproductive health priorities of women
      living with human immunodeficiency virus (HIV) and to allow the values and
      preferences of such women to be considered in the development of new guidelines.
      METHODS: A core team created a global reference group of 14 women living with HIV
      and together they developed a global community online survey. The survey, which
      contained mandatory and optional questions, was based on an appreciative enquiry
      approach in which the life-cycle experiences of women living with HIV were
      investigated. The same set of questions was also used in focus group discussions
      led by the global reference group. FINDINGS: The study covered 945 women (832 in
      the survey and 113 in the focus groups) aged 15-72 years in 94 countries. Among
      the respondents to the optional survey questions, 89.0% (427/480) feared or had
      experienced gender-based violence, 56.7% (177/312) had had an unplanned
      pregnancy, 72.3% (227/314) had received advice on safe conception and 58.8%
      (489/832) had suffered poor mental health after they had discovered their HIV
      positive status. CONCLUSION: The sexual and reproductive health needs and rights
      of women living with HIV are complex and require a stronger response from the
      health sector. The online survey placed the voices of women living with HIV at
      the start of the development of new global guidelines. Although not possible in
      some contexts and populations, a similar approach would merit replication in the
      development of guidelines for many other health considerations.

PMID- 27034518
TI  - Modelling the impact of raising tobacco taxes on public health and finance.
AB  - OBJECTIVE: To investigate the potential for tobacco tax to contribute to the 2030
      agenda for sustainable development by reducing tobacco use, saving lives and
      generating tax revenues. METHODS: A model of the global cigarette market in 2014-
      developed using data for 181 countries--was used to quantify the impact of
      raising cigarette excise in each country by one international dollar (I$) per 20
      cigarette pack. All currencies were converted into I$ using purchasing power
      parity exchange rates. The results were summarized by income group and region.
      FINDINGS: According to our model, the tax increase would lead the mean retail
      price of cigarettes to increase by 42%--from 3.20 to 4.55 I$ per 20-cigarette
      pack. The prevalence of daily smoking would fall by 9%--from 14.1% to 12.9% of
      adults--resulting in 66 million fewer smokers and 15 million fewer smoking
      attributable deaths among the adults who were alive in 2014. Cigarette excise
      revenue would increase by 47%--from 402 billion to 593 billion I$--giving an
      extra 190 billion I$s in revenue. This, in turn, could help create the fiscal
      space required to finance development priorities. For example, if the extra
      revenue was allocated to health budgets, public expenditure on health could
      increase by 4% globally. CONCLUSION: Tobacco taxation can prevent millions of
      smoking-attributable deaths throughout the world and contribute to achieving the
      sustainable development goals. There is also potential for tobacco taxation to
      create the fiscal space needed to finance development, particularly in low- and
      middle-income countries.

PMID- 27034519
TI  - Trends in socioeconomic disparities in a rapid under-five mortality transition: a
      longitudinal study in the United Republic of Tanzania.
AB  - OBJECTIVE: To explore trends in socioeconomic disparities and under-five
      mortality rates in rural parts of the United Republic of Tanzania between 2000
      and 2011. METHODS: We used longitudinal data on births, deaths, migrations,
      maternal educational attainment and household characteristics from the Ifakara
      and Rufiji health and demographic surveillance systems. We estimated hazard
      ratios (HR) for associations between mortality and maternal educational
      attainment or relative household wealth, using Cox hazard regression models.
      FINDINGS: The under-five mortality rate declined in Ifakara from 132.7 deaths per
      1000 live births (95% confidence interval, CI: 119.3-147.4) in 2000 to 66.2 (95%
      CI: 59.0-74.3) in 2011 and in Rufiji from 118.4 deaths per 1000 live births (95%
      CI: 107.1-130.7) in 2000 to 76.2 (95% CI: 66.7-86.9) in 2011. Combining both
      sites, in 2000-2001, the risk of dying for children of uneducated mothers was
      1.44 (95% CI: 1.08-1.92) higher than for children of mothers who had received
      education beyond primary school and in 2010-2011, the HR was 1.18 (95% CI: 0.90
      1.55). In contrast, mortality disparities between richest and poorest quintiles
      worsened in Rufiji, from 1.20 (95% CI: 0.99-1.47) in 2000-2001 to 1.48 (95% CI:
      1.15-1.89) in 2010-2011, while in Ifakara, disparities narrowed from 1.30 (95%
      CI: 1.09-1.55) to 1.15 (95% CI: 0.95-1.39) in the same period. CONCLUSION: While
      childhood survival has improved, mortality disparities still persist, suggesting
      a need for policies and programmes that both reduce child mortality and address
      socioeconomic disparities.

PMID- 27034520
TI  - The role of drug vendors in improving basic health-care services in Nigeria.
AB  - OBJECTIVE: To characterize patent and proprietary medicine vendors and shops in
      Nigeria and to assess their ability to help improve access to high-quality,
      primary health-care services. METHODS: In 2013 and 2014, a census of patent and
      proprietary medicine shops in 16 states of Nigeria was carried out to determine:
      (i) the size and coverage of the sector; (ii) the basic characteristics of shops
      and their staff; and (iii) the range of products stocked for priority health
      services, particularly for malaria, diarrhoea and family planning. The influence
      of the medical training of people in charge of the shops on the health-care
      products stocked and registration with official bodies was assessed by regression
      analysis. FINDINGS: The number of shops per 100,000 population was higher in
      southern than in northern states, but the average percentage of people in charge
      with medical training across local government areas was higher in northern
      states: 52.6% versus 29.7% in southern states. Shops headed by a person with
      medical training were significantly more likely to stock artemisinin-based
      combination therapy, oral rehydration salts, zinc, injectable contraceptives and
      intrauterine contraceptive devices. However, these shops were less likely to be
      registered with the National Association of Patent and Proprietary Medicine
      Dealers and more likely to be registered with the regulatory body, the Pharmacist
      Council of Nigeria. CONCLUSION: Many patent and proprietary medicine vendors in
      Nigeria were medically trained. With additional training and oversight, they
      could help improve access to basic health-care services. Specifically, vendors
      with medical training could participate in task-shifting interventions.

PMID- 27034521
TI  - Assessment of universal health coverage for adults aged 50 years or older with
      chronic illness in six middle-income countries.
AB  - OBJECTIVE: To assess universal health coverage for adults aged 50 years or older
      with chronic illness in China, Ghana, India, Mexico, the Russian Federation and
      South Africa. METHODS: We obtained data on 16,631 participants aged 50 years or
      older who had at least one diagnosed chronic condition from the World Health
      Organization Study on Global Ageing and Adult Health. Access to basic chronic
      care and financial hardship were assessed and the influence of health insurance
      and rural or urban residence was determined by logistic regression analysis.
      FINDINGS: The weighted proportion of participants with access to basic chronic
      care ranged from 20.6% in Mexico to 47.6% in South Africa. Access rates were
      unequally distributed and disadvantaged poor people, except in South Africa where
      primary health care is free to all. Rural residence did not affect access. The
      proportion with catastrophic out-of-pocket expenditure for the last outpatient
      visit ranged from 14.5% in China to 54.8% in Ghana. Financial hardship was more
      common among the poor in most countries but affected all income groups. Health
      insurance generally increased access to care but gave insufficient protection
      against financial hardship. CONCLUSION: No country provided access to basic
      chronic care for more than half of the participants with chronic illness. The
      poor were less likely to receive care and more likely to face financial hardship
      in most countries. However, inequity of access was not fully determined by the
      level of economic development or insurance coverage. Future health reforms should
      aim to improve service quality and increase democratic oversight of health care.

PMID- 27034522
TI  - A review of national health surveys in India.
AB  - Several rounds of national health surveys have generated a vast amount of data in
      India since 1992. We describe and compare the key health information gathered,
      assess the availability of health data in the public domain, and review
      publications resulting from the National Family Health Survey (NFHS), the
      District Level Household Survey (DLHS) and the Annual Health Survey (AHS). We
      highlight issues that need attention to improve the usefulness of the surveys in
      monitoring changing trends in India's disease burden: (i) inadequate coverage of
      noncommunicable diseases, injuries and some major communicable diseases; (ii)
      modest comparability between surveys on the key themes of child and maternal
      mortality and immunization to understand trends over time; (iii) short time
      intervals between the most recent survey rounds; and (iv) delays in making
      individual-level data available for analysis in the public domain. We identified
      337 publications using NFHS data, in contrast only 48 and three publications were
      using data from the DLHS and AHS respectively. As national surveys are resource
      intensive, it would be prudent to maximize their benefits. We suggest that India
      plan for a single major national health survey at five-year intervals in
      consultation with key stakeholders. This could cover additional major causes of
      the disease burden and their risk factors, as well as causes of death and adult
      mortality rate estimation. If done in a standardized manner, such a survey would
      provide useable and timely data to inform health interventions and facilitate
      assessment of their impact on population health.

PMID- 27034523
TI  - An approach for setting evidence-based and stakeholder-informed research
      priorities in low- and middle-income countries.
AB  - To derive evidence-based and stakeholder-informed research priorities for
      implementation in African settings, the international research consortium
      Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+)
      developed and applied a pragmatic approach. First, an online survey and face-to
      face consultation between CEBHA+ partners and policy-makers generated priority
      research areas. Second, evidence maps for these priority research areas
      identified gaps and related priority research questions. Finally, study protocols
      were developed for inclusion within a grant proposal. Policy and practice
      representatives were involved throughout the process. Tuberculosis, diabetes,
      hypertension and road traffic injuries were selected as priority research areas.
      Evidence maps covered screening and models of care for diabetes and hypertension,
      population-level prevention of diabetes and hypertension and their risk factors,
      and prevention and management of road traffic injuries. Analysis of these maps
      yielded three priority research questions on hypertension and diabetes and one on
      road traffic injuries. The four resulting study protocols employ a broad range of
      primary and secondary research methods; a fifth promotes an integrated
      methodological approach across all research activities. The CEBHA+ approach, in
      particular evidence mapping, helped to formulate research questions and study
      protocols that would be owned by African partners, fill gaps in the evidence
      base, address policy and practice needs and be feasible given the existing
      research infrastructure and expertise. The consortium believes that the
      continuous involvement of decision-makers throughout the research process is an
      important means of ensuring that studies are relevant to the African context and
      that findings are rapidly implemented. 

PMID- 27034524
TI  - Where is the policy in health policy and systems research agenda?

PMID- 27034525
TI  - Corrigendum.

PMID- 27034526
TI  - Integer sequence discovery from small graphs.
AB  - We have exhaustively enumerated all simple, connected graphs of a finite order
      and have computed a selection of invariants over this set. Integer sequences were
      constructed from these invariants and checked against the Online Encyclopedia of
      Integer Sequences (OEIS). 141 new sequences were added and six sequences were
      extended. From the graph database, we were able to programmatically suggest
      relationships among the invariants. It will be shown that we can readily
      visualize any sequence of graphs with a given criteria. The code has been
      released as an open-source framework for further analysis and the database was
      constructed to be extensible to invariants not considered in this work.

PMID- 27034527
TI  - Evaluation of environmental and intrinsic factors that contribute to stereotypic
      behavior in captive rhesus macaques (Macaca mulatta).
AB  - Full body repetitive behaviors, known as motor stereotypic behaviors (MSBs), are
      one of the most commonly seen abnormal behaviors in captive non-human primates,
      and are frequently used as a behavioral measure of well-being. The main goal of
      this paper was to examine the role of environmental factors (i.e., foraging
      enrichment and socialization) and intrinsic factors (i.e., temperament and
      origin) in the development of MSB in rhesus macaques living in cages. MSB was
      assessed during short annual observations in which a trained observer recorded a
      monkey's behavior for 5 min, followed by a 3-min novel object test. Data were
      collected over 11 years, totaling 9805 observations. We compared MSB for animals
      with and without foraging enrichment, and across three socialization conditions:
      full contact pairing, protected contact socialization (partners physically
      separated by widely spaced bars), and single housing. In addition, we evaluated
      whether individual differences in response to a novel object and ancestral origin
      (i.e., China vs. India), predicted MSB expression during the annual observations.
      Data were analyzed using generalized mixed effects modeling, with the best
      fitting models chosen using Akaike Information Criterion. Subjects were at lowest
      risk for MSB when a foraging device was present (p < 0.05), and when in full
      contact social housing (p < 0.001). There was no statistically significant
      difference in MSB between subjects that were single housed and subjects housed in
      protected contact pairs. In addition, subjects that never touched the novel
      object were significantly less likely to exhibit MSB than those that touched the
      object immediately (p < 0.001) or within 3 min (p < 0.001). Finally, monkeys with
      some degree of Chinese ancestry were significantly more likely to display MSB
      than Indian-origin monkeys (p < 0.05). These results add to the growing body of
      literature on factors that can contribute to the development of MSB.

PMID- 27034528
TI  - Dispositional mindfulness and rejection sensitivity: The critical role of
      nonjudgment.
AB  - The pain of rejection is a crucial component of normal social functioning;
      however, heightened sensitivity to rejection can be impairing in numerous ways.
      Mindfulness-based interventions have been effective with several populations
      characterized by elevated sensitivity to rejection; however, the relationship
      between mindfulness and rejection sensitivity has been largely unstudied. The
      present study examines associations between rejection sensitivity and multiple
      dimensions of dispositional mindfulness, with the hypothesis that a nonjudgmental
      orientation to inner experiences would be both associated with decreased
      rejection sensitivity and attenuate the impact of sensitivity to rejection on
      general negative affect. A cross-sectional sample of undergraduates (n = 451)
      completed self-report measures of rejection sensitivity, dispositional
      mindfulness, and trait-level negative affect. Significant zero-order correlations
      and independent effects were observed between most facets of dispositional
      mindfulness and rejection sensitivity, with nonjudging demonstrating the largest
      effects. As predicted, rejection sensitivity was associated with negative
      affectivity for people low in nonjudging (beta = .27, t = 5.12, p < .001) but not
      for people high in nonjudging (beta = .06, t = .99, p = .324). These findings
      provide preliminary support for mindfulness, specifically the nonjudging
      dimension, as a protective factor against rejection sensitivity and its effects
      on affect.

PMID- 27034529
TI  - Residential exposure to air toxics is linked to lower grade point averages among
      school children in El Paso, Texas, USA.
AB  - Children in low-income neighborhoods tend to be disproportionately exposed to
      environmental toxicants. This is cause for concern because exposure to
      environmental toxicants negatively affect health, which can impair academic
      success. To date, it is unknown if associations between air toxics and academic
      performance found in previous school-level studies persist when studying
      individual children. In pairing the National Air Toxics Assessment (NATA) risk
      estimates for respiratory and diesel particulate matter risk disaggregated by
      source, with individual-level data collected through a mail survey, this paper
      examines the effects of exposure to residential environmental toxics on academic
      performance for individual children for the first time and adjusts for school
      level effects using generalized estimating equations. We find that higher levels
      of residential air toxics, especially those from non-road mobile sources, are
      statistically significantly associated with lower grade point averages among
      fourth and fifth grade school children in El Paso (Texas, USA).

PMID- 27034530
TI  - Quantitative ELISA-Like Immunohistochemistry of Fibroblast Growth Factor 23 in
      Diagnosis of Tumor-Induced Osteomalacia and Clinical Characteristics of the
      Disease.
AB  - Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder and
      fibroblast growth factor 23 (FGF23) plays a key role in its pathogenesis. This
      study was conducted to describe a novel FGF23 detecting procedure and describe
      clinical features of the disease. Fourteen TIO cases were retrieved and FGF23
      expression was measured by quantitative ELISA-like immunohistochemistry using
      formalin-fixed and paraffin-embedded tissues. As summarized from 14 TIO cases,
      clinical features of TIO were long-standing history of osteomalacia,
      hypophosphatemia, and urinary phosphate wasting. The associated tumors were
      mostly benign phosphaturic mesenchymal tumors mixed connective tissue variant
      (PMTMCT) which could be located anywhere on the body, and most of them could be
      localized by conventional examinations and octreotide scanning. By quantitative
      ELISA-like immunohistochemistry, all the 14 TIO cases had high FGF23 expression
      (median 0.69, 25%-75% interquartile 0.57-1.10, compared with 26 non-TIO tumors of
      median 0.07, 25%-75% interquartile 0.05-0.11, p < 0.001). The quantitative ELISA
      like immunohistochemistry was a feasible and reproducible procedure to detect the
      high FGF23 expression in formalin-fixed and paraffin-embedded biopsies or
      specimens. Since TIO was often delay-diagnosed or misdiagnosed, clinicians and
      pathologists should be aware of TIO and PMTMCT, respectively. 

PMID- 27034531
TI  - Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and
      Epigenetic Network Derived from Next-Generation Sequencing Data.
AB  - Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and
      the development of cancer. By using the available omics data, including those
      from next-generation sequencing (NGS), genome-wide methylation profiling,
      candidate integrated genetic and epigenetic network (IGEN) analysis, and drug
      response genome-wide microarray analysis, we constructed an IGEN system based on
      three coupling regression models that characterize protein-protein interaction
      networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks
      (MRNs), and epigenetic regulatory networks (ERNs). By applying system
      identification method and principal genome-wide network projection (PGNP) to IGEN
      analysis, we identified the core network biomarkers to investigate bladder
      carcinogenic mechanisms and design multiple drug combinations for treating
      bladder cancer with minimal side-effects. The progression of DNA repair and cell
      proliferation in stage 1 bladder cancer ultimately results not only in the
      derepression of miR-200a and miR-200b but also in the regulation of the TNF
      pathway to metastasis-related genes or proteins, cell proliferation, and DNA
      repair in stage 4 bladder cancer. We designed a multiple drug combination
      comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1
      bladder cancer with minimal side-effects, and another multiple drug combination
      comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage
      4 bladder cancer with minimal side-effects. 

PMID- 27034532
TI  - Human Hemochromatosis Protein (HFE) Immunoperoxidase Stain Highlights
      Choriocarcinoma within Mixed Germ Cell Tumors.
AB  - Identification of choriocarcinoma within a germ cell tumor can have major
      implications for the subsequent staging and treatment of testicular neoplasms.
      Immunoperoxidase staining greatly enhances the speed and sensitivity of
      identifying occult, though clinically significant, tumor components. In mixed
      germ cell tumors, staining for beta-human chorionic gonadotropin (beta-hCG) has
      been historically used to assess for the presence and burden of choriocarcinoma.
      However, current beta-hCG stains produce variable, intense staining of
      trophoblastic elements and surrounding tissues, clouding the assessment of true
      positive staining. Human hemochromatosis protein (HFE) is a membrane bound
      mediator of iron transport expressed at high levels within placenta.
      Additionally, previous reports have demonstrated that choriocarcinoma cell lines
      express HFE, although in vivo expression had not been examined. To address
      whether HFE can stain trophoblastic elements, HFE immunohistochemistry was
      conducted in choriocarcinoma (n = 4), mixed germ cell tumors (n = 11), seminoma
      (n = 4), and placenta (n = 11). HFE consistently demonstrated cytoplasmic and
      membranous staining, highlighting both syncytiotrophoblasts and cytotrophoblasts
      within choriocarcinoma and placenta. Staining of intratumoral white blood cells
      was observed within seminomas and mixed germ cell tumors, corroborating prior
      reports stating that HFE highlights monocytes and macrophages. Taken together,
      HFE may serve as an alternative target from beta-hCG for immunoperoxidase studies
      when highlighting choriocarcinoma. 

PMID- 27034533
TI  - HER2 Protein Overexpression and Gene Amplification in Plasmacytoid Urothelial
      Carcinoma of the Urinary Bladder.
AB  - AIM: HER2 overexpression has been reported in a minority of urothelial
      carcinomas, but little is known about HER2 protein expression and gene
      alterations in plasmacytoid urothelial carcinoma, a rare and aggressive variant.
      The aim of this study was to clarify the HER2 status in plasmacytoid urothelial
      carcinomas. METHODS: Six cases of plasmacytoid urothelial carcinoma were
      included, in which we evaluated HER2 protein expression by immunohistochemistry
      (IHC) and HER2 gene amplification by fluorescence in situ hybridization (FISH).
      RESULTS: The patients' ages ranged from 57 to 83 years (mean age, 71 years). Five
      patients were male and one was female. The ratio of the plasmacytoid component
      ranged from 30% to 100% (mean, 77%). HER2 expression score was 3+ in 4 cases, 2+
      in one case, and negative in one case. HER2 gene amplification was positive in 3
      cases, of which 2 cases showed a 3+ HER2 IHC score but one case was negative for
      HER2 IHC. Another 2 cases showed equivocal HER2 FISH results, and one remaining
      case was negative for HER2 FISH. CONCLUSION: Our observation that plasmacytoid
      urothelial carcinomas frequently demonstrated HER2 protein overexpression
      provides supporting evidence that HER2 may be a potential therapeutic target for
      plasmacytoid urothelial carcinoma.

PMID- 27034534
TI  - A Proportional Hazards Regression Model for the Sub-distribution with Covariates
      Adjusted Censoring Weight for Competing Risks Data.
AB  - With competing risks data, one often needs to assess the treatment and covariate
      effects on the cumulative incidence function. Fine and Gray proposed a
      proportional hazards regression model for the subdistribution of a competing risk
      with the assumption that the censoring distribution and the covariates are
      independent. Covariate-dependent censoring sometimes occurs in medical studies.
      In this paper, we study the proportional hazards regression model for the
      subdistribution of a competing risk with proper adjustments for covariate
      dependent censoring. We consider a covariate-adjusted weight function by fitting
      the Cox model for the censoring distribution and using the predictive probability
      for each individual. Our simulation study shows that the covariate-adjusted
      weight estimator is basically unbiased when the censoring time depends on the
      covariates, and the covariate-adjusted weight approach works well for the
      variance estimator as well. We illustrate our methods with bone marrow transplant
      data from the Center for International Blood and Marrow Transplant Research
      (CIBMTR). Here cancer relapse and death in complete remission are two competing
      risks.

PMID- 27034535
TI  - Effect of climate change on sporulation of the teleomorphs of Leptosphaeria
      species causing stem canker of brassicas.
AB  - Leptosphaeria maculans and L. biglobosa are closely related sibling fungal
      pathogens that cause phoma leaf spotting, stem canker (blackleg) and stem
      necrosis of oilseed rape (Brassica napus). The disease is distributed worldwide,
      and it is one of the main causes of considerable decrease in seed yield and
      quality. Information about the time of ascospore release at a particular location
      provides important data for decision making in plant protection, thereby enabling
      fungicides to be used only when necessary and at optimal times and doses.
      Although the pathogens have been studied very extensively, the effect of climate
      change on the frequencies and distributions of their aerially dispersed primary
      inoculum has not been reported to date. We have collected a large dataset of
      spore counts from Poznan, located in central-west part of Poland, and studied the
      relationships between climate and the daily concentrations of airborne propagules
      over a period of 17 years (1998-2014). The average air temperature and
      precipitation for the time of development of pseudothecia and ascospore release
      (July-November), increased during the years under study at the rates of 0.1 
      degrees C and 6.3 mm per year. The day of the year (DOY) for the first detection
      of spores, as well as the date with maximum of spores, shifted from 270 to 248
      DOY, and from 315 to 265 DOY, respectively. The acceleration of the former
      parameter by 22 days and the latter by 50 days has great influence on the
      severity of stem canker of oilseed rape.

PMID- 27034536
TI  - A 10-year study of Alternaria and Cladosporium in two Polish cities (Szczecin and
      Cracow) and relationship with the meteorological parameters.
AB  - Alternaria and Cladosporium spores belong to the most frequent and allergenic
      particles in bioaerosol in the temperate climate. The investigation of Alternaria
      and Cladosporium spore concentrations was performed in two cities in Poland,
      Szczecin and Cracow, in 2004-2013. The meteorological parameters taken to assess
      their impact on fungal spores were average, maximum and minimum temperature,
      relative humidity and average wind velocity. In order to reveal whether changes
      in dynamics of spore seasons are driven by meteorological conditions, ordination
      methods were applied. Canonical correspondence analysis was used to explore
      redundancy among the predictors (meteorological parameters). Prior to ordination
      analyses, the data were log(x)-transformed. Concentrations of Alternaria and
      Cladosporium spores were significantly higher in Szczecin comparing to Cracow,
      but it was also observed the decreasing trend in the spore concentrations in
      Szczecin. As regards temperature, it was higher in Cracow and was still
      increasing in the studied years. Relative humidity and wind velocity were
      significantly lower in Cracow. In Szczecin meteorological conditions did not
      explain changes in spore season characteristics (insignificant redundancy
      analysis models), while in Cracow's redundancy analysis models indicated that
      spore season parameters were in over 40 % determined by meteorological
      conditions, mainly air temperature and wind velocity. If they increase, the peak
      value, total number of spores and their average concentrations in a season will
      also increase.

PMID- 27034537
TI  - Warm and dry weather accelerates and elongates Cladosporium spore seasons in
      Poland.
AB  - Temperature is the environmental factor that systematically changes for decades
      and, as in plants and animals, can significantly affect the growth and
      development of fungi, including the abundance of their sporulation. During the
      time of study (2010-2012), a rapid increase in air temperature was observed in
      Poland, which coincided with the substantial decrease in rainfall. The increase
      in annual mean temperatures at three monitoring sites of this study was 0.9 
      degrees C in Lublin and Rzeszow (east Poland) and 2.0  degrees C in Poznan (west
      Poland). Such warming of air masses was comparable to the average global air
      temperature rise in the period of 1880-2012 accounting for 0.85  degrees C, as
      reported by the Intergovernmental Panel on Climate Change. Moreover, there was a
      substantial decrease in rainfall, ranging from 32.7 % (Poznan) to 43.0 %
      (Rzeszow). We have demonstrated that under such conditions the mean and median
      values of total Cladosporium spore counts significantly increased and the spore
      seasons were greatly accelerated. Moreover, earlier start and later end of the
      season caused its extension, lasting from over 20 days in Rzeszow to around 60
      days in Lublin and Poznan, when the cumulative amount of 5-95 % of spores was
      considered. The time of reaching the cumulative amount of 50 % of spores was up
      to 25 days earlier (difference in Poznan between 2010 and 2012). There was also a
      striking acceleration of the date of the maximal Cladosporium spore concentration
      per cubic metre of air (26 days for Lublin, 43 for Poznan and 56 for Rzeszow).

PMID- 27034538
TI  - The Legacy of the 1968 Fair Housing Act.
AB  - Civil rights activists in 1968 hoped that the passage of the Fair Housing Act
      would lead to the residential desegregation of American society. In this article
      I assess the degree to which this hope has been fulfilled. I begin by reviewing
      how the black ghetto came to be a universal feature of American cities during the
      20th Century and the means by which high levels of black segregation were
      achieved. I then describe the legislative maneuvers required to pass the Fair
      Housing Act and review its enforcement provisions to assess its potential for
      achieving desegregation. After examining trends in residential segregation since
      1970, I conclude with an appraisal of the prospects for integration as we move
      toward the 50th anniversary of the Act's passage.

PMID- 27034539
TI  - Study of an adaptive bolus chasing CT angiography.
AB  - To improve imaging quality and to reduce contrast dose and radiation exposure, an
      adaptive bolus chasing CT angiography was proposed so that the bolus peak
      position and the imaging aperture can be synchronized. The performance of the
      proposed adaptive bolus chasing CT angiography was experimentally evaluated based
      on the actual bolus dynamics. The experimental results show that the controlled
      table position and the bolus peak position were highly consistent. The results
      clearly demonstrate that the proposed adaptive bolus chasing CT angiography that
      synchronizes the bolus peak position with the imaging aperture by a simple
      adaptive system is computationally and clinically feasible. Similar techniques
      may also be applied to conventional angiography to improve imaging quality and to
      reduce contrast dose and/or radiation exposure.

PMID- 27034540
TI  - The characteristics of Mohs surgery performed by dermatologists who learned the
      procedure during residency training or through postgraduate courses and
      observational preceptorships.
AB  - Little is known about the practice characteristics of Mohs surgery performed by
      physicians who learned the procedure during their dermatology residency training
      or through postresidency courses and observational preceptorships. All published
      reports have investigated Mohs surgeons trained in postresidency fellowships.
      This report presents the results of a multicenter prospective cohort study
      evaluating 1834 consecutive Mohs surgery cases performed during the same 6-month
      period by 9 Mohs surgeons who learned the technique in residency or in
      postresidency courses and observational preceptorships. One major complication
      was reported, a hematoma requiring outpatient drainage in an emergency room.
      There were 54 (2.9%) short-term complications, including 20 (1.1%) infections, 17
      (0.9%) wound dehiscences, 9 (0.5%) cases of skin flap necrosis, and 8 (0.4%)
      hematomas or postoperative bleeding episodes. These complication rates and the
      data evaluating tumor type, anatomic location, primary vs. recurrent tumor
      status, tumor size, postoperative wound size, number of Mohs surgery stages, and
      repair type compare favorably to previously published reports. 

PMID- 27034542
TI  - Safety and efficacy of packed red blood cell transfusions at different doses in
      very low birth weight infants.
AB  - This double-blinded, randomized, crossover study evaluated the safety and
      effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC) transfusions
      versus 15 mL/kg aliquot transfusions in very low birth weight (VLBW) infants with
      anemia. The study enrolled 22 hemodynamically stable VLBW infants requiring PRBC
      transfusions, with a mean gestational age of 25.7 +/- 2.2 weeks and birth weight
      of 804 +/- 261 g. Each infant was randomized to receive one of two treatment
      sequences: 15 mL/kg followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The
      infants were monitored during and after transfusions, and the efficacy and safety
      of the treatments were evaluated. Infants had higher posttransfusion hemoglobin
      (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels (38.6 g/dL vs 34.4 g/dL,
      P < 0.01) following 20 mL/kg PRBC transfusions when compared to 15 mL/kg
      transfusions. There were no differences in the incidence of tachypnea,
      hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign
      instability between groups. In conclusion, high-volume PRBC transfusions (20
      mL/kg) were associated with higher posttransfusion hemoglobin and hematocrit
      levels but no adverse effects. Higher-volume transfusions may reduce the need for
      multiple transfusions and therefore the number of donors the infant is exposed
      to. 

PMID- 27034541
TI  - Virtual reality and brain computer interface in neurorehabilitation.
AB  - The potential benefit of technology to enhance recovery after central nervous
      system injuries is an area of increasing interest and exploration. The primary
      emphasis to date has been motor recovery/augmentation and communication. This
      paper introduces two original studies to demonstrate how advanced technology may
      be integrated into subacute rehabilitation. The first study addresses the
      feasibility of brain computer interface with patients on an inpatient spinal cord
      injury unit. The second study explores the validity of two virtual environments
      with acquired brain injury as part of an intensive outpatient neurorehabilitation
      program. These preliminary studies support the feasibility of advanced
      technologies in the subacute stage of neurorehabilitation. These modalities were
      well tolerated by participants and could be incorporated into patients' inpatient
      and outpatient rehabilitation regimens without schedule disruptions. This paper
      expands the limited literature base regarding the use of advanced technologies in
      the early stages of recovery for neurorehabilitation populations and speaks
      favorably to the potential integration of brain computer interface and virtual
      reality technologies as part of a multidisciplinary treatment program. 

PMID- 27034544
TI  - Invited Commentary.

PMID- 27034543
TI  - Review of behavioral health integration in primary care at Baylor Scott and White
      Healthcare, Central Region.
AB  - The integration of behavioral health services in primary care has been referred
      to in many ways, but ultimately refers to common structures and processes.
      Behavioral health is integrated into primary care because it increases the
      effectiveness and efficiency of providing care and reduces costs in the care of
      primary care patients. Reimbursement is one factor, if not the main factor, that
      determines the level of integration that can be achieved. The federal health
      reform agenda supports changes that will eventually permit behavioral health to
      be fully integrated and will allow the health of the population to be the primary
      target of intervention. In an effort to develop more integrated services at
      Baylor Scott and White Healthcare, models of integration are reviewed and the
      advantages and disadvantages of each model are discussed. Recommendations to
      increase integration include adopting a disease management model with care
      management, planned guideline-based stepped care, follow-up, and treatment
      monitoring. Population-based interventions can be completed at the pace of the
      development of alternative reimbursement methods. The program should be based
      upon patient-centered medical home standards, and research is needed throughout
      the program development process. 

PMID- 27034545
TI  - Medical and surgical care during the American Civil War, 1861-1865.
AB  - This review describes medical and surgical care during the American Civil War.
      This era is often referred to in a negative way as the Middle Ages of medicine in
      the United States. Many misconceptions exist regarding the quality of care during
      the war. It is commonly believed that surgery was often done without anesthesia,
      that many unnecessary amputations were done, and that care was not state of the
      art for the times. None of these assertions is true. Physicians were practicing
      in an era before the germ theory of disease was established, before sterile
      technique and antisepsis were known, with very few effective medications, and
      often operating 48 to 72 hours with no sleep. Each side was woefully unprepared,
      in all aspects, for the extent of the war and misjudged the degree to which each
      would fight for their cause. Despite this, many medical advances and discoveries
      occurred as a result of the work of dedicated physicians on both sides of the
      conflict. 

PMID- 27034546
TI  - Exercise-induced acute compartment syndrome in a young man, occurring after a
      short race.
AB  - We describe a case of exercise-induced acute compartment syndrome (ACS) in a 23
      year-old man who presented to his primary care physician 48 hours after he
      attempted to run a 5K race. He noticed searing pain in his left leg after the
      first half mile but had no other symptoms. He was referred to the emergency
      department and diagnosed with ACS, and a fasciotomy was done. A presentation of
      limb pain that is out of proportion to a known or suspected injury should prompt
      consideration of ACS. Early recognition and surgical management are essential to
      achieving the best possible outcome. 

PMID- 27034547
TI  - Table tipping and a near-miss fall after unlocking a surgical table holding a
      morbidly obese patient.
AB  - Presented is a case report of a morbidly obese patient who experienced a near
      miss fall in the operating room due to several factors. We present the importance
      of recognizing the change in fulcrum location on a Steris 4085 operating table
      when the bed is in the unlocked versus the locked position. This small change, in
      the presence of morbid obesity and reverse orientation of the table, can lead to
      an unsafe situation in which the patient's weight can cause the table to tip. We
      present potential ways to avoid this complication. 

PMID- 27034548
TI  - Use of ultrasound guidance to remove entrapped stimulating popliteal catheters.
AB  - Peripheral nerve catheters are beneficial for continuous pain relief following
      surgery or trauma to an extremity. However, spring-loaded peripheral nerve
      catheters can become uncoiled and entrapped, resulting in difficulty in catheter
      removal. We present two cases where ultrasound guidance provided significant
      assistance in the safe removal of entrapped peripheral nerve catheters without
      neurologic sequelae. One of the catheters was adhered to nearby tissue, and one
      had become uncoiled and anchored in place by the distal tip. Guidelines for the
      safe management of entrapped catheters are suggested, including the use of saline
      injections through the catheter under ultrasound guidance to assist in the
      evaluation and removal of the catheters. 

PMID- 27034549
TI  - Baclofen-responsive hiccups after esophageal stenting for malignancy-related
      dysphagia.
AB  - Hiccups can have multiple causes, including esophageal lesions. Hiccups after
      insertion of self-expanding metallic stents have been reported occasionally
      following stenting for lesions of the gastroesophageal junction. We report a
      patient who developed hiccups after insertion of a stent for squamous cell
      carcinoma of the proximal esophagus. The hiccups responded only to the initiation
      of baclofen therapy. 

PMID- 27034550
TI  - Specificity of testing in a cardiac rehabilitation setting resulting in a
      patient's return to high-intensity outdoor activity following aortic dissection
      repair.
AB  - A 66-year-old man who had undergone aortic dissection repair a year earlier
      sought to assess the feasibility of returning to the high-intensity outdoor
      activities he had long enjoyed. In response to his inquiry, the cardiac
      rehabilitation staff at Baylor Hamilton Heart and Vascular Hospital designed a
      comprehensive testing plan that simulated the specific movements and anticipated
      cardiac requirements associated with his goal activities. The activities included
      1) lifting and manipulating a 50-pound suitcase, 2) hiking to the top of Half
      Dome in California's Yosemite National Park, and 3) scuba diving. To illustrate
      our approach, we describe some of the tests that were performed and report the
      results. After analyzing the detailed physiological data collected during
      testing, we provided the patient with an exercise prescription and specific
      guidelines that he could use to gauge his level of physical exertion during his
      outdoor adventures. Within approximately 6 months of testing, he successfully
      performed the goal activities without adverse symptoms. 

PMID- 27034551
TI  - Invited Commentary: Simulated performance testing to determine the aortic
      dissection patient's potential for vigorous physical activity.

PMID- 27034552
TI  - Cardiovascular autonomic neuropathy.
AB  - Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of
      a 22-year-old man with multiple manifestations of this disease, including
      weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which
      occurred 2 years after his type 1 diabetes diagnosis. He exhibited
      parasympathetic denervation with resting tachycardia and exercise intolerance but
      also had evidence of orthostatic hypotension, which suggests sympathetic
      denervation. He did not have complete cardiovascular autonomic reflex testing,
      which would have been helpful, but improved with aggressive diabetes treatment
      and the increase of beta-blockade. It is important to identify these patients to
      understand their signs and symptoms and consider appropriate therapies. 

PMID- 27034553
TI  - Cardiac arrest refractory to standard intervention in atypical Timothy syndrome
      (LQT8 type 2).
AB  - Timothy syndrome (TS) is a rare, multisystem disorder most commonly associated
      with profound QTc prolongation and cutaneous dysmorphia arising from mutations of
      the L-type calcium channel. We present a case of a 12-day-old newborn who
      presented with respiratory distress and cyanosis. Diagnostic workup was notable
      for multiple cardiac abnormalities, and genetic analysis was consistent with an
      exon 8 mutation of the CACNA1C gene, which is diagnostic for TS type 2 (atypical
      TS). This patient presented with a novel constellation of symptoms, without
      dysmorphic features, and with a more moderate QTc interval. The heterogeneity of
      phenotypes suggests that this disorder may be characterized by variable
      expressivity or a spectrum of disease rather than a clearly defined syndrome. 

PMID- 27034554
TI  - Holter monitor recordings in a man who snores.

PMID- 27034555
TI  - An interesting electrocardiogram.

PMID- 27034556
TI  - Takotsubo cardiomyopathy after administration of norepinephrine.
AB  - Stress-induced cardiomyopathy is a syndrome of transient cardiac dysfunction with
      no clear pathophysiology. It is thought to be secondary to catecholamine surge.
      The mechanism by which catecholamine can induce transient cardiac dysfunction is
      unknown. We present a case of a patient who developed stress-induced
      cardiomyopathy after she was administered norepinephrine due to a nursing error. 

PMID- 27034557
TI  - Acute myocardial infarction with isolated congenitally corrected transposition of
      the great arteries.
AB  - Congenital cardiac abnormalities diagnosed at the time of acute coronary syndrome
      are rare. A 43-year-old man presented to the emergency department complaining of
      recurring, severe chest pain. Subsequent emergent coronary angiography
      demonstrated unusual coronary anatomy: 1) one small caliber bifurcating vessel
      originating from the right sinus of Valsalva; 2) one very large vessel arising
      from the posterior sinus; and 3) no coronary artery from the normal left sinus of
      Valsalva. The large vessel from the posterior sinus was totally occluded in its
      midportion and was treated with intravascular ultrasound-guided percutaneous
      coronary intervention. Further diagnostic workup, including two-dimensional
      transthoracic echocardiogram and computed tomographic coronary angiography,
      demonstrated isolated corrected transposition of the great arteries with a
      dilated systemic ventricle and systolic dysfunction with an ejection fraction of
      30%. The patient's clinical course was complicated by recurrent nonsustained
      ventricular tachycardia, treated with medical therapy and a dual-chamber
      implantable cardioverter defibrillator. This case is an example of a common
      clinical presentation with a very uncommon congenital heart disorder. Similar
      cases may become more frequent as the number of adult congenital heart patients
      increases in the population. 

PMID- 27034558
TI  - Isolated congenitally corrected transposition of the great arteries with
      dextroversion discovered incidentally in a patient with cocaine-induced acute
      myocardial infarction.
AB  - Complex cardiac congenital anomalies can occasionally be found in adult patients
      who have no knowledge of their condition. Here we present the case of a 27-year
      old man with cocaine-induced acute myocardial infarction in whom an isolated
      congenitally corrected transposition of the great arteries with dextroversion was
      discovered incidentally. 

PMID- 27034559
TI  - Invited Commentary: The specialty of adult congenital heart disease.

PMID- 27034560
TI  - Surgical considerations for the explantation of the Parachute left ventricular
      partitioning device and the implantation of the HeartMate II left ventricular
      assist device.
AB  - Chronic heart failure is the leading cause of death in the world. With newer
      therapies, the burden of this disease has decreased; however, a significant
      number of patients remain refractive to existing therapies. Myocardial infarction
      often leads to ventricular remodeling and eventually contributes to heart
      failure. The ParachuteTM (Cardiokinetix, Menlo Park, CA) is the first device
      designed for percutaneous ventricular restoration therapy, which reduces left
      ventricular volume and minimizes the risk of open surgical procedures. For the
      first time, we report a case of explantation of the Parachute ventricular
      partitioning device and transition to a HeartMate IITM left ventricular assist
      device and the surgical considerations for a successful outcome. 

PMID- 27034561
TI  - Intracranial aneurysm and sildenafil.
AB  - Sildenafil is one of the most commonly used drugs for the treatment of erectile
      dysfunction. To date, we found five reported cases of intracerebral bleeding and
      two reported cases of subarachnoid hemorrhage related to sildenafil use. We
      report a 49-year-old hypertensive and diabetic patient who presented with acute
      pulmonary edema and loss of consciousness following ingestion of 100 mg of
      sildenafil prior to sexual intercourse. He was not previously aware of the
      presence of an aneurysm and had no family history of it. Computed tomography of
      his head revealed a subarachnoid hemorrhage due to rupture of a saccular aneurysm
      with subsequent repeat hemorrhage within a few hours of presentation. A sudden
      increase in blood pressure led to pulmonary edema. Studies have shown that
      sildenafil acts on phosphodiesterase-1, -2 and -5 receptors and leads to a
      secondary increase in intracerebral circulation and vasodilatory effects, leading
      to sympathetic overactivity which increases the risk for intracranial bleeding. 

PMID- 27034562
TI  - Infective endocarditis caused by Klebsiella oxytoca in an intravenous drug user
      with cancer.
AB  - Infective endocarditis caused by Klebsiella species is rare, with most isolates
      being K. pneumoniae. We report the case of a 24-year-old intravenous drug user
      with newly diagnosed seminoma who developed K. oxytoca endocarditis. In addition
      to having K. oxytoca isolated from blood culture, cultures of that species were
      obtained from a retroperitoneal metastasis found on original presentation. 

PMID- 27034563
TI  - Rapidly enlarging neck mass in a neonate causing airway compromise.
AB  - Up to 20% of all congenital pediatric head and neck masses are branchial cleft
      cysts. Second branchial cleft cysts account for 95% of branchial anomalies, and
      fourth branchial cleft cysts are the rarest type. Their typical presentations
      include non-life-threatening symptoms, such as drainage, skin irritations, minor
      swelling, and tenderness. We describe a 5-week-old neonate with increasing
      stridor secondary to a rapidly growing neck mass. Imaging and surgical excision
      confirmed the mass to be an infected fourth branchial cleft cyst. 

PMID- 27034564
TI  - Serendipitous discovery of peritoneal mesothelioma.
AB  - We present the case of a 64-year-old patient with a history of Birt-Hogg-Dube
      syndrome, polycystic kidney disease treated with renal transplantation in May
      2013, and multiple types of skin cancers, including malignant melanoma. He
      presented for lymphoscintigraphy for sentinel lymph node identification of the
      melanoma. Subsequent biopsy of the right axillary sentinel lymph node yielded a
      diagnosis of epithelial type malignant mesothelioma without a known primary
      tumor. Follow-up positron emission tomography with 2-deoxy-2-(fluorine-18)fluoro
      D-glucose integrated with computed tomography (F-18 FDG PET/CT) demonstrated
      several suspicious hypermetabolic abdominal masses that were later confirmed to
      be epithelial-type mesothelioma via percutaneous biopsy. 

PMID- 27034565
TI  - Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema in Pneumocystis
      jiroveci pneumonia in AIDS.
AB  - Pneumomediastinum, the presence of free air within the mediastinal cavity, is
      sometimes accompanied by subcutaneous emphysema and pneumorrhachis (air within
      the spinal canal). We report the case of a 28-year-old man with previously
      undiagnosed HIV who was diagnosed with extensive pneumomediastinum,
      pneumorrhachis, and subcutaneous emphysema secondary to Pneumocystis jiroveci
      pneumonia after presenting with chest pain, dyspnea, and central cyanosis.
      Surgical consultation was requested, but a conservative approach of observation
      proved sufficient as the free air was resorbed into the surrounding tissues. 

PMID- 27034566
TI  - Multiple dural-based hemangiopericytomas.
AB  - Here we report the case of a 57-year-old man who underwent resection of a dural
      based hemangiopericytoma (HPC) in the left frontoparietal region. The patient was
      treated with radiation therapy and remained symptom-free for 10 years. At 67
      years of age, he presented with a mass in the left frontal region near the same
      area as the first tumor, in addition to a separate smaller mass in the right
      middle cranial fossa. Resection of the larger left frontal mass revealed an HPC.
      Follow-up imaging 9 months later showed a significant increase in size of the
      right middle cranial fossa mass. This third mass was resected, and histological
      examination also demonstrated an HPC. 

PMID- 27034567
TI  - Colorectal cancer implant in an external hemorrhoidal skin tag.
AB  - External hemorrhoidal skin tags are generally benign. Colorectal cancer
      metastases to the squamous epithelium of perianal skin tags without other
      evidence of disseminated disease is a very rare finding. We present the case of a
      61-year-old man with metastasis to an external hemorrhoidal skin tag from a
      midrectal primary adenocarcinoma. This case report highlights the importance of
      close examination of the anus during surgical planning for colorectal cancers.
      Abnormal findings of the perianal skin suggesting an implant or metastatic
      disease warrant biopsy, as distal spread and seeding can occur. In our patient,
      this finding appropriately changed surgical management. 

PMID- 27034568
TI  - Bilateral synchronous plasmacytoma of the testis.
AB  - Extramedullary plasmacytoma (EMP) is usually seen in the head and neck regions
      and in the upper respiratory, gastrointestinal, and central nervous systems.
      Testis is a rare site for EMP, and bilateral synchronous testicular plasmacytoma
      occurring as an isolated event at initial presentation has been reported only
      once previously. We present herein the second such report in a 70-year-old man
      who underwent bilateral orchidectomy. 

PMID- 27034569
TI  - Presentation of epidermolytic acanthomas as multiple tan papules on the vulva.
AB  - Epidermolytic hyperkeratosis is a histological reaction pattern seen in a variety
      of disease processes, including epidermolytic ichthyosis, Vorner's epidermolytic
      palmoplantar keratoderma, epidermal nevus, and solitary epidermolytic acanthoma.
      Here we present the case of a 59-year-old woman with multiple asymptomatic
      papules on her vulva. Clinical differential diagnoses included condyloma
      acuminata, seborrheic keratoses, bowenoid papulosis, adnexal tumors, and papular
      acantholytic dyskeratosis. Shave biopsy revealed findings consistent with
      epidermolytic hyperkeratosis. This case represents an interesting presentation of
      focally disseminated vulvar epidermolytic acanthomas and highlights the
      importance of a biopsy in establishing this diagnosis. 

PMID- 27034570
TI  - Rumpel-Leede phenomenon presenting as a hypertensive urgency.
AB  - Rumpel-Leede (R-L) phenomenon is the rare event in which the small dermal
      capillaries of an extremity rupture in response to application of a compressive
      device to that extremity, such as when inflating a cuff during noninvasive blood
      pressure monitoring or when applying a tourniquet to draw blood. This capillary
      rupture results in formation of a petechial rash distal to the compressive
      device. R-L phenomenon is believed to occur most often in patients with
      underlying vascular disease, such as diabetes mellitus or thrombocytopenia. R-L
      phenomenon is most often benign, though it may rarely be associated with pain and
      discomfort. There is no treatment for this condition apart from treatment of the
      underlying vascular disease or thrombocytopenia. We report a 57-year-old woman
      who presented with hypertensive urgency and experienced R-L phenomenon during
      blood pressure cuff inflation. 

PMID- 27034571
TI  - Arm pain and erythema.
AB  - Pyomyositis can be a difficult diagnosis to make, as it can mimic many other
      disease processes. Various laboratory studies can be abnormal with pyomyositis,
      but none are specific to the disease. Early disease can generally be treated with
      antibiotics alone, whereas advanced disease frequently requires emergent surgical
      intervention with significant resuscitation. We describe a case of pyomyositis of
      the right arm. 

PMID- 27034572
TI  - Rheumatoid meningitis associated with infliximab.
AB  - We present a patient who had rheumatoid meningitis while on infliximab, a tumor
      necrosis factor alpha (TNF-alpha) inhibitor, which initially presented as
      transient ischemic attacks. Although our patient had been stable on infliximab
      for several years, her neurologic symptoms improved when her infliximab was held
      due to active infection and then recurred after reinitiation of therapy.
      Rheumatoid meningitis is exceedingly rare; however, there have been several other
      reports of rheumatoid meningitis developing in patients on TNF-alpha inhibitor
      therapy. 

PMID- 27034573
TI  - Cryptococcal meningitis in a patient with sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease characterized by the presence
      of noncaseating granulomas. Case reports have previously described an association
      between sarcoidosis and cryptococcal infection, but many of these patients were
      receiving immunosuppression at the time of diagnosis or had limited cutaneous
      disease. We report a case of cryptococcal meningitis in a 65-year-old man with a
      new presentation of sarcoidosis who was not receiving immunosuppressive
      medications. 

PMID- 27034574
TI  - Thyroid hormone resistance and its management.
AB  - The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome
      of thyroid hormone resistance, is an inherited condition that occurs in 1 of
      40,000 live births characterized by a reduced responsiveness of target tissues to
      thyroid hormone due to mutations on the thyroid hormone receptor. Patients can
      present with symptoms of hyperthyroidism or hypothyroidism. They usually have
      elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone
      level. Due to their nonspecific symptomatic presentation, these patients can be
      misdiagnosed if the primary care physician is not familiar with the condition.
      This can result in frustration for the patient and sometimes unnecessary invasive
      treatment such as radioactive iodine ablation, as in the case presented herein. 

PMID- 27034575
TI  - The price of a 15-year delay in diagnosis of Sheehan's syndrome.
AB  - We describe a case of a 48-year-old woman who presented with a 15-year history of
      recurrent episodes of hypoglycemia and hyponatremia leading to altered behavior
      and generalized seizures. She underwent full clinical assessment, endocrine
      tests, and a pituitary magnetic resonance scan that showed pananterior
      hypopituitarism secondary to postpartum pituitary necrosis (Sheehan's syndrome).
      She was commenced on appropriate hormone replacement therapy, which led to
      significant improvement in lethargy, anorexia, muscle weakness, and episodes of
      hypoglycemia. In addition to the alleviation of her physical symptoms, she
      experienced a significant improvement in her psychological well-being and
      reduction in hospital visits. This case illustrates the impact of delay in
      diagnosis of an easily treatable medical condition and its socioeconomic
      implications, especially for the population of a developing country like India. 

PMID- 27034576
TI  - Linezolid-induced serotonin toxicity in a patient not taking monoamine oxidase
      inhibitors or serotonin receptor antagonists.
AB  - Linezolid is an oxazolidinone antibiotic with weak monoamine oxidase (MAO) type A
      and MAO type B inhibitory effects. Linezolid has been associated with serotonin
      toxicity when used concomitantly with multiple medications that are known to
      increase serotonin concentrations. We report the case of a 65-year-old woman with
      signs and symptoms of serotonin toxicity following administration of linezolid
      for treatment of methicillin-resistant Staphylococcus aureus pneumonia. 

PMID- 27034577
TI  - Facts and ideas from anywhere.

PMID- 27034578
TI  - Simulation verification of SNR and parallel imaging improvements by ICE-decoupled
      loop array in MRI.
AB  - Transmit/receive L/C loop arrays with the induced current elimination (ICE) or
      magnetic wall decoupling method has shown high signal-to-noise (SNR) and
      excellent parallel imaging ability for MR imaging at ultrahigh fields, e.g., 7 T.
      In this study, we aim to numerically analyze the performance of an eight-channel
      ICE-decoupled loop array at 7 T. Three dimensional (3-D) electromagnetic (EM) and
      radiofrequency (RF) circuit co-simulation approach was employed. The values of
      all capacitors were obtained by optimizing the S-parameters of all coil elements.
      The EM simulation accurately modeled the coil structure, the phantom and the
      excitation. All coil elements were well matched to 50 ohm and the isolation
      between any two coil elements was better -15 dB. The simulated S parameters were
      exactly similar with the experimental results, indicating the simulation results
      were reliable. Compared with the conventional capacitively decoupled array, the
      ICE-decoupled array had higher sensitivity at the peripheral areas of the image
      subjects due to the shielding effect of the decoupling loops. The increased
      receive sensitivity resulted in an improvement of signal intensity and SNR for
      the ICE-decoupled array.

PMID- 27034579
TI  - Ultrasound diagnostics of renal artery stenosis: Stenosis criteria, CEUS and
      recurrent in-stent stenosis.
AB  - BACKGROUND AND PURPOSE: As a non-invasive, side effect-free and cost-effective
      method, ultrasonography represents the method of choice for the diagnosis of
      renal artery stenosis. Four different criteria in total, including two direct
      criteria in peak systolic velocity (PSV) and renal aortic ratio (RAR) and two
      indirect criteria in resistance index (RI) and acceleration time (AT) for the
      measurement of relevant renal artery stenosis are described, each demonstrating
      highly variable accuracy in studies. Furthermore, there is controversy over the
      degree beyond which stenosis becomes therapeutically relevant and which
      ultrasound PSV is diagnostically relevant in terms of stenosis grading. MATERIAL
      AND METHODS: This article gives a critical review based on a selective literature
      search on measurement methodology and the validity of ultrasound in renal artery
      stenosis. A critical evaluation of methods and a presentation of measurement
      principles to establish the most precise measurement method possible compared
      with the gold standard angiography, as well as an evaluation of the importance of
      computed tomography angiography (CTA) and magnetic resonance angiography (MRA).
      RESULTS AND CONCLUSIONS: The PSV provides high sensitivity and specificity as a
      direct measurement method in stenosis detection and grading. Most studies found
      sensitivities and specificities of 85-90 % for > 50 % stenosis at a PSV > 180-200
      cm/s in ROC curve analysis. Other methods, such as the ratio of the PSV in the
      aorta to the PSV in the renal artery (RAR) or indirect criteria, such as side to
      side differences in RI (dRI) or AT can be additionally used to improve accuracy.
      Contrast-enhanced ultrasound improves accuracy by means of echo contrast
      enhancement. Although in the past only high-grade stenosis was considered
      relevant for treatment, a drop in pressure of > 20 mmHg in > 50 % stenosis (PSV
      180 cm/s) is classified as relevant for increased renin secretion. Stenosis in
      fibromuscular dysplasia can be reliably graded according to the continuity
      equation. Although the available studies on the grading of in-stent restenosis
      are the subject of controversy, there is a tendency to assume higher cut-off
      values for PSV and RAR. Whilst MRA and CTA demonstrate an accuracy of > 90 %,
      this is at the cost of possible side effects for patients, particularly in the
      case of pre-existing renal parenchymal damage. ADDITIONAL ONLINE MATERIAL: This
      article includes two additional video sequences on visualizing renal artery
      stenosis. This supplemental material can be found under:
      dx.doi.org/10.1007/s00772-015-0060-3.

PMID- 27034580
TI  - Epidemiology and inpatient treatment of vascular diseases in Germany: English
      Version.
AB  - BACKGROUND: Non-cardiac vascular diseases account for approximately 10 % of the
      total burden of disease in the German population as measured in disability
      adjusted life years (DALY). Thus, from the social perspective, much attention
      should be paid to optimization of the provision of vascular services especially
      in elderly people. OBJECTIVES: This article describes the structure of inpatient
      care and the provision of vascular treatment as well as age- and gender-specific
      hospital incidence rates of vascular diseases in Germany between 2005 and 2013.
      MATERIALS AND METHODS: Secondary data analysis is based on basic data from German
      hospitals as well as nationwide aggregated data from the diagnosis-related
      groups' statistics from the Federal Statistical Office. RESULTS: Since 2005, the
      incidence of non-cardiac vascular diseases has increased and showed a significant
      dependency on sex and age. In general, men were affected consistently more
      frequently by vascular diseases. In contrast, hospital admission rates due to
      varicose veins or acute ischemia of the legs were higher in women. Treatment of
      arterial diseases was performed predominantly in general surgery units or
      departments for vascular surgery. From 1991 to 2013, the number of hospitals
      employing specialists for vascular surgery almost doubled, and the number of
      vascular surgeons working full-time in German hospitals was nearly tripled.
      Endovascular approaches were used particularly for revascularization of
      peripheral arteries as well as aortic aneurysm repair. In contrast, carotid
      surgery as well as peripheral embolectomy were predominately performed using open
      surgical techniques. CONCLUSIONS: Since 1991, the increasing need for vascular
      services for patients has been met by continuously growing structures for the
      provision of vascular surgical treatment; however, the suitability and efficiency
      of provision of vascular services could only be assessed in an appropriate way by
      using more differentiated and disaggregated data. ADDITIONAL MATERIAL AVAILABLE
      ONLINE: Additional information is available in the online version of this article
      (doi:10.1007/s00772-015-0095-5).

PMID- 27034581
TI  - Biodegradable polymeric stents for vascular application in a porcine carotid
      artery model: English version.
AB  - Over the past years the development of biodegradable polymeric stents has made
      great progress; nevertheless, essential problems must still be solved.
      Modifications in design and chemical composition should optimize the quality of
      biodegradable stents and remove the weaknesses. New biodegradable poly-L
      lactide/poly-4-hydroxybutyrate (PLLA/P4HB) stents and permanent 316L stents were
      implantedendovascularly into both common carotid arteries of 10 domestic pigs. At
      4 weeks following implantation, computed tomography (CT) angiography was carried
      out to identify the distal degree of stenosis. The PLLA/P4HB group showed a
      considerably lower distal degree of stenosis by additional oral application of
      atorvastatin (mean 39.81 +/- 8.57 %) compared to the untreated PLLA/P4HB group
      without atorvastatin (mean 52.05 +/- 5.80 %). The 316L stents showed no
      differences in the degree of distal stenosis between the group treated with
      atorvastatin (mean 44.21 +/- 2.34 %) and the untreated group (mean 35.65 +/- 3.72
      %). Biodegradable PLLA/P4HB stents generally represent a promising approach to
      resolving the existing problems in the use of permanent stents. Restitutio ad
      integrum is only achievable if a stent is completely degraded.

PMID- 27034582
TI  - Non-linear VLBI station motions and their impact on the celestial reference frame
      and Earth orientation parameters.
AB  - The increasing accuracy and growing time span of Very Long Baseline
      Interferometry (VLBI) observations allow the determination of seasonal signals in
      station positions which still remain unmodelled in conventional analysis
      approaches. In this study we focus on the impact of the neglected seasonal
      signals in the station displacement on the celestial reference frame and Earth
      orientation parameters. We estimate empirical harmonic models for selected
      stations within a global solution of all suitable VLBI sessions and create mean
      annual models by stacking yearly time series of station positions which are then
      entered a priori in the analysis of VLBI observations. Our results reveal that
      there is no systematic propagation of the seasonal signal into the orientation of
      celestial reference frame but position changes occur for radio sources observed
      non-evenly over the year. On the other hand, the omitted seasonal harmonic signal
      in horizontal station coordinates propagates directly into the Earth rotation
      parameters causing differences of several tens of microarcseconds.

PMID- 27034583
TI  - Pushing the Intuitions behind Moral Internalism.

PMID- 27034584
TI  - Long-Term Functional and Psychosocial Consequences and Health Care Provision
      after Traumatic Brain Injury.

PMID- 27034585
TI  - Assessment of Internal Jugular Vein Size in Healthy Subjects with Magnetic
      Resonance and Semiautomatic Processing.
AB  - Background and Objectives. The hypothesized link between extracranial venous
      abnormalities and some neurological disorders awoke interest in the investigation
      of the internal jugular veins (IJVs). However, different IJV cross-sectional area
      (CSA) values are currently reported in literature. In this study, we introduced a
      semiautomatic method to measure and normalize the CSA and the degree of
      circularity (Circ) of IJVs along their whole length. Methods. Thirty-six healthy
      subjects (31.22 +/- 9.29 years) were recruited and the 2D time-of-flight magnetic
      resonance venography was acquired with a 1.5 T Siemens scanner. The IJV were
      segmented on an axial slice, the contours were propagated in 3D. Then, IJV CSA
      and Circ were computed between the first and the seventh cervical levels (C1-C7)
      and normalized among subjects. Inter- and intrarater repeatability were assessed.
      Results. IJV CSA and Circ were significantly different among cervical levels (p <
      0.001). A trend for side difference was observed for CSA (larger right IJV, p =
      0.06), but not for Circ (p = 0.5). Excellent inter- and intrarater repeatability
      was obtained for all the measures. Conclusion. This study proposed a reliable
      semiautomatic method able to measure the IJV area and shape along C1-C7, and
      suitable for defining the normality thresholds for future clinical studies. 

PMID- 27034586
TI  - The Response of Macrophages and Neutrophils to Hypoxia in the Context of Cancer
      and Other Inflammatory Diseases.
AB  - Lack of oxygen (hypoxia) is a hallmark of a multitude of acute and chronic
      diseases and can be either beneficial or detrimental for organ restitution and
      recovery. In the context of inflammation, hypoxia is particularly important and
      can significantly influence the course of inflammatory diseases. Macrophages and
      neutrophils, the chief cellular components of innate immunity, display distinct
      properties when exposed to hypoxic conditions. Virtually every aspect of
      macrophage and neutrophil function is affected by hypoxia, amongst others,
      morphology, migration, chemotaxis, adherence to endothelial cells, bacterial
      killing, differentiation/polarization, and protumorigenic activity. Prominent
      arenas of macrophage and neutrophil function, for example, acute/chronic
      inflammation and the microenvironment of solid tumors, are characterized by low
      oxygen levels, demonstrating the paramount importance of the hypoxic response for
      proper function of these cells. Members of the hypoxia-inducible transcription
      factor (HIF) family emerged as pivotal molecular regulators of macrophages and
      neutrophils. In this review, we will summarize the molecular responses of
      macrophages and neutrophils to hypoxia in the context of cancer and other chronic
      inflammatory diseases and discuss the potential avenues for therapeutic
      intervention that arise from this knowledge. 

PMID- 27034587
TI  - Klotho Contributes to Pravastatin Effect on Suppressing IL-6 Production in
      Endothelial Cells.
AB  - Both statins and klotho have been shown to be beneficial in vascular diseases.
      Interleukin- (IL-) 6 is evidenced as an indicator reflecting the stability of
      atherosclerotic plaque and involved in the pathogenesis of artery
      atherosclerosis. However, the relationship between statin, klotho, and IL-6 under
      an inflammatory environment is unknown. Using primary human umbilical vein
      endothelial cells (HUVECs), pravastatin dose-dependently induced klotho
      expression in contrast to remarkable suppression to IL-6 expressions determined
      by qRT-PCR. Moreover, TNF-alpha-induced IL-6 was partly but significantly blunted
      by pravastatin detected by ELISA. To further study the role of klotho in
      modulating IL-6 expression, endothelial cells with klotho overexpression were
      treated with TNF-alpha. Importantly, TNF-alpha-induced IL-6 production was
      markedly attenuated in klotho-overexpressed cells. In agreement with in vitro
      data, a marked reduction of klotho mRNA expression was found in isolated
      peripheral blood mononuclear cells (PBMCs) from patients with atherosclerosis.
      Together, these data suggested that pravastatin could suppress IL-6 production
      via promoting klotho expression in endothelial cells under inflammatory stimuli. 

PMID- 27034588
TI  - Analysis of Cytokine Levers in Pleural Effusions of Tuberculous Pleurisy and
      Tuberculous Empyema.
AB  - The aim is to examine whether the interleukin-1beta (IL-1beta), IL-2, IL-6, tumor
      necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type-1 (PAI
      1), and tissue plasminogen activator (t-PA) levels were different in pleural
      effusions of tuberculous pleurisy and tuberculous empyema. IL-1beta, IL-2, IL-6,
      TNF-alpha, PAI-1, and t-PA levels in pleural fluids of 40 patients with
      tuberculous pleurisy and 38 patients with tuberculous empyema were measured. The
      levels of IL-1beta, PAI-1, and t-PA in the pleural effusions were different
      between tuberculous pleurisy and tuberculous empyema; it could be helpful to
      differentiate the two diseases. The levels of PAI-1, IL-1beta were higher and t
      PA, IL-6 were lower in pleural effusions of the patients with tuberculous empyema
      and who must undergo operation than the patients who could be treated with closed
      drainage and anti-TB chemotheraphy. These indications may be helpful to evaluate
      whether the patient needs the operation. 

PMID- 27034590
TI  - NK Cell-Dependent Growth Inhibition of Lewis Lung Cancer by Yu-Ping-Feng, an
      Ancient Chinese Herbal Formula.
AB  - Little is known about Yu-Ping-Feng (YPF), a typical Chinese herbal decoction, for
      its antitumor efficacy in non-small-cell lung cancer (NSCLC). Here, we found that
      YPF significantly inhibited the growth of Lewis lung cancer, prolonged the
      survival of tumor-bearing mice, promoted NK cell tumor infiltration, increased
      the population of NK cells in spleen, and enhanced NK cell-mediated killing
      activity. The growth suppression of tumors by YPF was significantly reversed by
      the depletion of NK cells. Furthermore, we found that YPF significantly
      downregulated the expression of TGF-beta, indoleamine 2,3-dioxygenase, and IL-10
      in tumor microenvironment. These results demonstrated that YPF has a NK cell
      dependent inhibitory effect on Lewis lung cancer. 

PMID- 27034591
TI  - Sex Hormones Enhance Gingival Inflammation without Affecting IL-1beta and TNF
      alpha in Periodontally Healthy Women during Pregnancy.
AB  - Hormones (progesterone and estradiol) change greatly during pregnancy; however,
      the mechanism of hormonal changes on gingival inflammation is still unclear. This
      study is to evaluate the effects of hormonal changes during pregnancy on gingival
      inflammation and interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha
      (TNF-alpha) in gingival crevicular fluid (GCF). 30 periodontally healthy pregnant
      women were evaluated in the first, second, and third trimesters. 20 periodontally
      healthy nonpregnant women were evaluated twice (once per subsequent month).
      Clinical parameters including probing pocket depth (PPD), bleeding index (BI),
      gingival index (GI), clinical attachment level (CAL), and plaque index (PLI) were
      recorded. GCF levels of IL-1beta and TNF-alpha and serum levels of progesterone
      and estradiol were measured. From the data, despite low PLI, BI and GI increased
      significantly during pregnancy; however, no significant changes in PLI, CAL, IL
      1beta, or TNF-alpha GCF levels were observed. Although IL-1beta, not TNF-alpha,
      was higher in pregnant group than in nonpregnant group, they showed no
      correlation with serum hormone levels during pregnancy. GI and BI showed
      significant positive correlation with serum hormone levels during pregnancy. This
      study suggests that sex hormone increase during pregnancy might have an effect on
      inflammatory status of gingiva, independent of IL-1beta and TNF-alpha in GCF. 

PMID- 27034589
TI  - Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells.
AB  - Dendritic cells present in the digestive tract are constantly exposed to
      environmental antigens, commensal flora, and invading pathogens. Under steady
      state conditions, these cells have high tolerogenic potential, triggering
      differentiation of regulatory T cells to protect the host from unwanted
      proinflammatory immune responses to innocuous antigens or commensals. On the
      other hand, these cells must discriminate between commensal flora and invading
      pathogens and mount powerful immune response against pathogens. A potential
      result of unbalanced tolerogenic versus proinflammatory responses mediated by
      dendritic cells is associated with chronic inflammatory conditions, such as
      Crohn's disease, ulcerative colitis, food allergies, and celiac disease. Herein,
      we review the dendritic cell population involved in mediating tolerance and
      immunity in mucosal surfaces, the progress in unveiling their development in
      vivo, and factors that can influence their functions. 

PMID- 27034592
TI  - Anti-Inflammatory and Antimicrobial Effects of Estradiol in Bovine Mammary
      Epithelial Cells during Staphylococcus aureus Internalization.
AB  - 17beta-Estradiol (E2), the predominant sexual hormone in females, is associated
      with the modulation of the innate immune response (IIR), and changes in its
      levels at parturition are related to intramammary infections, such as mastitis.
      In bovine mammary epithelial cells (bMECs), E2 regulates differentiation and
      proliferation, but its immunomodulatory functions have not been explored.
      Staphylococcus aureus is the predominant pathogen causing mastitis, which can
      persist intracellularly in bMECs. The aim of this work was to analyze whether E2
      modulates the IIR of bMECs during S. aureus internalization. bMECs treated with
      E2 (50 pg/mL, 24 h) reduced bacteria internalization (~50%). The host receptors
      alpha5beta1 and TLR2 do not participate in this reduction. However, E2 activates
      ERalpha and modulates the IIR reducing the S. aureus induced-mRNA expression of
      TNF-alpha (~50%) and IL-1beta (90%). E2 also decreased the secretion of these
      cytokines as well as IL-6 production; however, in infected bMECs, E2 induced the
      secretion of IL-1beta. Furthermore, E2 upregulates the expression of the
      antimicrobial peptides DEFB1, BNBD5, and psoriasin S100A7 (~5-, 3-, and 6-fold,
      resp.). In addition, E2 induced the production of antimicrobial compounds in bMEC
      culture medium, which, together with the modulation of the IIR, could be related
      to the reduction of S. aureus internalization. 

PMID- 27034593
TI  - IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction
      via PLCbeta3 during Airway Inflammation.
AB  - Mucus secretion is often uncontrolled in many airway inflammatory diseases of
      humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus
      overproduction, and hypersecretion is important to alleviate airway inflammation
      in these diseases. However, the regulatory signaling pathway controlling mucus
      overproduction has not been fully identified yet. In this study, we report that
      the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway
      inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC
      gene expression via the inhibition of Galphaq-induced Ca(2+) signaling. IL-1ra
      inhibited IL-1alpha protein expression and secretion, and vice versa.
      Interestingly, ATP/P2Y2-induced IL-1ra and IL-1alpha secretion were both mediated
      by PLCbeta3. A dominant-negative mutation in the PDZ-binding domain of PLCbeta3
      inhibited ATP/P2Y2-induced IL-1ra and IL-1alpha secretion. IL-1alpha in the
      presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree
      and for a longer duration than the ATP/P2Y2 complex itself, which was
      dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra
      exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through
      inhibition of IL-1alpha secretion, to maintain the mucus homeostasis in the
      airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed
      airway microenvironments in respiratory diseases. 

PMID- 27034595
TI  - NLRP3 Inflammasome Plays an Important Role in the Pathogenesis of Collagen
      Induced Arthritis.
AB  - OBJECTIVE: To investigate the relationship between NLRP3 and the pathogenesis of
      collagen-induced arthritis. METHODS: We used the collagen-induced arthritis (CIA)
      mouse model. The mice were divided into two groups: the model group (CIA, n = 16)
      and the control group (Normal, n = 8). The mice were sacrificed seven weeks after
      immunization. The arthritis score and imaging evaluation (X-rays, Micro-CT, and
      MRI) were performed. Synovial tissue NLRP3 expression and peripheral blood
      cytokine levels were analyzed. RESULTS: The arthritis score (6.00 +/- 2.52),
      imaging score (4.63 +/- 0.92), and synovial tissue NLRP3 expression (4.00 +/-
      2.03) significantly increased in the CIA mice. The expression of synovial NLRP3
      was positively correlated with arthritis clinical and radiographic scores (r =
      0.792 and r = 0.669, resp.). CONCLUSIONS: The synovial NLRP3 expression increased
      at the early onset of RA. Synovial NLRP3 expression level was correlated with the
      clinical arthritis severity and extent of radiological destruction, suggesting
      that NLRP3 is involved in the pathogenesis of RA.

PMID- 27034596
TI  - Enhancing Nutrition Security via India's National Food Security Act: Using an Axe
      instead of a Scalpel?
AB  - In September 2013, India passed a historic National Food Security Act. This paper
      examines the potential impact of the two central pillars of this act - expansion
      of the Public Distribution System and strengthening of the Integrated Child
      Development Schemes - on child nutrition. Using new data from the India Human
      Development Survey of 2011-12, this paper shows that access to subsidized grains
      via PDS is not related to improved child nutrition, and while ICDS seems to be
      related to lower child undernutrition, it has a limited reach in spite of the
      universalization of the program. The paper suggests that a tiered strategy in
      dealing with child undernutrition that starts with the identification of
      undernourished children and districts and follows through with different
      strategies for dealing with severe, acute malnutrition, followed by a focus on
      moderate malnutrition, could be more effective than the existing focus on cereal
      distribution rooted in the NFSA.

PMID- 27034594
TI  - Double Roles of Macrophages in Human Neuroimmune Diseases and Their Animal
      Models.
AB  - Macrophages are important immune cells of the innate immune system that are
      involved in organ-specific homeostasis and contribute to both pathology and
      resolution of diseases including infections, cancer, obesity, atherosclerosis,
      and autoimmune disorders. Multiple lines of evidence point to macrophages as a
      remarkably heterogeneous cell type. Different phenotypes of macrophages exert
      either proinflammatory or anti-inflammatory roles depending on the cytokines and
      other mediators that they are exposed to in the local microenvironment.
      Proinflammatory macrophages secrete detrimental molecules to induce disease
      development, while anti-inflammatory macrophages produce beneficial mediators to
      promote disease recovery. The conversion of the phenotypes of macrophages can
      regulate the initiation, development, and recovery of autoimmune diseases. Human
      neuroimmune diseases majorly include multiple sclerosis (MS), neuromyelitis
      optica (NMO), myasthenia gravis (MG), and Guillain-Barre syndrome (GBS) and
      macrophages contribute to the pathogenesis of these neuroimmune diseases. In this
      review, we summarize the double roles of macrophage in neuroimmune diseases and
      their animal models to further explore the mechanisms of macrophages involved in
      the pathogenesis of these disorders, which may provide a potential therapeutic
      approach for these disorders in the future. 

PMID- 27034597
TI  - Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase
      Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous
      Preparation of Kalanchoe Pinnata Leaves.
AB  - BACKGROUND: Diabetes mellitus is a chronic metabolic disease that according to
      the World Health Organization affects more than 382 million people. The rise in
      diabetes mellitus coupled with the lack of an effective treatment has led many to
      investigate medicinal plants to identify a viable alternative. OBJECTIVE: To
      evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase)
      activities and antioxidant levels in streptozotocin-induced diabetic rats
      administered aqueous preparation of Kalanchoe pinnata leaves. MATERIALS AND
      METHODS: Diabetes mellitus was induced in rats by a single administration of
      streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K.
      pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14
      g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities,
      and antioxidant levels were determined. RESULTS: We noted weight loss and reduced
      food consumption in the treated diabetic group. Serum glucose levels were reduced
      in the treated diabetic group compared to the other groups. Superoxide dismutase
      activity and glutathione levels were not significantly elevated in the treated
      group compared to the diabetic group. However, serum catalase activity was
      significantly (P < 0.05) increased in the treated diabetic group compared to the
      other groups. Serum thiobarbituric acid reactive substances were not
      significantly altered among the groups. There was a significant (P < 0.05)
      increase in Mg(2+) ATPase activity and a nonsignificant increase in Na(+)/K(+)
      ATPase activity in the RBC membrane of the treated diabetic group compared to the
      diabetic group. CONCLUSION: The consumption of aqueous preparation of K. pinnata
      may accrue benefits in the management of diabetes by lowering oxidative stress
      often associated with the disease and improving the availability of cellular
      magnesium through an increase in the magnesium ATPase pump in the RBC membrane
      for increased cellular metabolism of glucose through the glycolytic pathway.
      SUMMARY: We noted weight loss and reduced food consumption in the diabetic rats
      treated with K. pinnata preparationSerum glucose levels were reduced in diabetic
      rats treated with K. pinnata preparationSerum catalase activity was significantly
      (P < 0.05) increased in diabetic rats treated with K. pinnata preparationWe also
      noted a significant (P < 0.05) increase in Mg(2+) ATPase activity in the RBC
      membranes of diabetic rats treated with K. pinnata preparationOverall, the
      consumption of aqueous preparation of K. pinnata lowered oxidative stress often
      associated with diabetes and improved availability of cellular magnesium through
      an increase in magnesium ATPase pump in the RBC membrane.

PMID- 27034599
TI  - Characterization of Anticancer Principles of Celosia argentea (Amaranthaceae).
AB  - BACKGROUND: An Indian origin, Celosia argentea is a weed growing during rainy
      season traditionally claimed for treating several ailments. Early researches on
      C. argentea were focused on the anti-cancer screening of seeds, with few reports
      on aerial parts. OBJECTIVE: To isolate and characterize bioactive compounds of
      aerial parts of C. argentea and evaluate their anticancer potential. MATERIALS
      AND METHODS: The methanolic aerial part extract was fractionated on column
      chromatography using chloroform: methanol mixture. The fractions; 80:20 and 95:5
      were purified on MCI-HP20 HPLC column. Chromatographically pure compounds were
      pooled, concentrated and characterized spectroscopically. The compounds were
      further screened for anti-oxidant and cytotoxic potential. RESULTS: Isolated
      compounds were confirmed as: (1) Luteolin-7-O-glucoside and (2) phenolic, 1-(4
      hydroxy-2-methoxybenzofuran-5-yl)-3-phenylpropane-1,3-dione. Both exhibited
      significant antioxidant potential with IC50 values of 20.80 and 21.30 MUg/ml for
      2,2-diphenyl-1-picrylhydrazyl assay (***P < 0.001) and significant Trolox
      equivalent antioxidant capacity (TEAC) values for 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) (*P < 0.05) and ferric reducing antioxidant
      potential assay (****P < 0.0001). In 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazoliumbromide assay, Compound 1 and 2 showed potent cytotoxicity against
      SiHa, HCT, MCF-7 cancer cell lines at 20 MUg/ml (****P < 0.0001) and 18 MUg/ml
      (**P < 0.01), respectively, without affecting the normal Vero cells. Both
      compounds enabled maximum reduction in cell viability at 50 MUg/ml against HT-29
      (***P < 0.001) and MCF-7 cell lines (**P < 0.01) in try pan blue viability assay.
      Apoptosis occurred at concentrations of 47.33 +/- 0.8 MUg/ml and 56.28 +/- 1.2
      MUg/ml for Compound 1 and 35.15 +/- 0.4 MUg/ml and 28.05 +/- 0.3 MUg/ml for
      Compound 2 for HT-29 and MCF-7 respectively. CONCLUSION: A novel anticancer
      phenolic compound; (1-(4-hydroxy-2-methoxybenzofuran-5-yl)-3-phenylpropane-1,3
      dione), isolated from aerial parts of C. argentea was a valuable finding of the
      research. SUMMARY: The present study validated the potential of the plant C.
      argentea as an antioxidant, and anticancer remedy with two valuable isolations.
      Although one of them is a known compound: Luteolin 7-0 glycoside, the other
      isolated phenolic compound;-{1-(4-hydroxy-2-methoxybenzofuran-5-yl)-3
      phenylpropane-1,3-dione}, is the first to be reported and thus can be considered
      as a valuable outcome of this research work.

PMID- 27034598
TI  - Ameliorative Effects of Chloroform Fraction of Cocos nucifera L. Husk Fiber
      Against Cisplatin-induced Toxicity in Rats.
AB  - BACKGROUND: Cisplatin (Cis) is used in the treatment of solid tumors and is known
      to elicit serious side effects. OBJECTIVE: The present study investigated the
      protective effects of chloroform fraction of Cocos nucifera husk fiber (CFCN)
      against Cis-induced organs' damage and chromosomal defect in rats. Quercetin
      (QUE), standard antioxidant, served as positive control. MATERIALS AND METHODS:
      Thirty male Wistar rats were assigned into six groups and treated with corn oil
      (control), Cis alone, Cis + CFCN, CFCN alone, Cis + QUE, and QUE alone. QUE and
      CFCN were given at 50 and 200 mg/kg/day, respectively, by oral gavage for 7 days
      before the rats were exposed to a single dose of Cis (10 mg/kg, intraperitoneal)
      at the last 36 h of study. RESULTS: Administration of Cis alone caused a
      significant (P < 0.05) increase in the levels of serum creatinine and urea by 72%
      and 70%, respectively, when compared with the control. The activity of serum
      aspartate aminotransferase was significantly (P < 0.05) increased while alanine
      aminotransferase and alkaline phosphatase were insignificantly (P > 0.05)
      affected in Cis-treated rats. Furthermore, the activities of hepatic and renal
      catalase, superoxide dismutase, glutathione S-transferase, glutathione
      peroxidase, and levels of reduced glutathione were significantly (P < 0.05)
      decreased in Cis-treated rats with concomitant elevation of malondialdehyde. Cis
      exposure increased the frequency of micro nucleated polychromatic erythrocytes
      (mPCE) by 92%. Pretreatment with CFCN inhibited lipid peroxidation, enhanced the
      activities of some antioxidative enzymes and reduced the frequency of mPCE.
      CONCLUSIONS: Chloroform fraction of CFCN may protect against organs damage by
      Cis. Further studies are required to determine the component of the plant
      responsible for this activity. SUMMARY: Cisplatin (Cis) is used in the treatment
      of solid tumors and is known to elicit serious side effects. This study
      investigated the protective effects of chloroform fraction of Cocos nucifera husk
      fiber (CFCN) against Cis-induced organs' damage while quercetin (QUE) served as
      standard antioxidant.Thirty male Wistar rats were assigned into six groups and
      treated with corn oil (Control), Cis alone, Cis + CFCN, CFCN alone, Cis + QUE and
      QUE alone.QUE and CFCN were given at 50 and 200 mg/kg/day respectively by oral
      gavage for seven days before the rats were exposed to a single dose of Cis
      (10mg/kg, i.p.) at the last 36 h of study. Results indicate that administration
      of Cis caused a significant (P<0.05) increase in the levels of serum creatinine
      and urea by 72% and 70% respectively.The activity of serum aspartate
      aminotransferase was significantly (P <0.05) increased while alanine
      aminotransferase and alkaline phosphatase were insignificantly (P>0.05) affected
      in Cis-treated rats.The activities of hepatic and renal catalase, superoxide
      dismutase, glutathione-s-transferase, glutathione peroxidase and levels of
      reduced glutathione were significantly (P<0.05) decreased in Cis-treated rats
      with concomitant elevation of malondialdehyde.Cis exposure increased the
      frequency of micronucleated polychromatic erythrocytes (mPCE) by 92%.Pretreatment
      with CFCN inhibited lipid peroxidation, enhanced the activities of some
      antioxidative enzymes and reduced the frequency of mPCE. The findings suggest
      that CFCN may protect against organs damage by cisplatin.Further studies are
      required to determine the component of the plant responsible for this activity.

PMID- 27034600
TI  - Assessment of Anti-Influenza Activity and Hemagglutination Inhibition of Plumbago
      indica and Allium sativum Extracts.
AB  - BACKGROUND: Human influenza is a seasonal disease associated with significant
      morbidity and mortality. Anti-flu ayurvedic/herbal medicines have played a
      significant role in fighting the virus pandemic. Plumbagin and allicin are
      commonly used ingredients in many therapeutic remedies, either alone or in
      conjunction with other natural substances. Evidence suggests that these extracts
      are associated with a variety of pharmacological activities. OBJECTIVE: To
      evaluate anti-influenza activity from Plumbago indica and Allium sativum extract
      against Influenza A (H1N1)pdm09. MATERIALS AND METHODS: Different extraction
      procedures were used to isolate the active ingredient in the solvent system, and
      quantitative HPLTC confirms the presence of plumbagin and allicin. The
      cytotoxicity was carried out on Madin-Darby Canine kidney cells, and the 50%
      cytotoxic concentration (CC50) values were below 20 mg/mL for both plant
      extracts. To assess the anti-influenza activity, two assays were employed,
      simultaneous and posttreatment assay. RESULTS: A. sativum methanolic and
      ethanolic extracts showed only 14% reduction in hemagglutination in contrast to
      P. indica which exhibited 100% reduction in both simultaneous and posttreatment
      assay at concentrations of 10 mg/mL, 5 mg/mL, and 1 mg/mL. CONCLUSIONS: Our
      results suggest that P. indica extracts are good candidates for anti-influenza
      therapy and should be used in medical treatment after further research. SUMMARY:
      The search for natural antiviral compounds from plants is a promising approach in
      the development of new therapeutic agents. In the past century, several
      scientific efforts have been directed toward identifying phytochemicals capable
      of inhibiting virus. Knowledge of ethnopharmacology can lead to new bioactive
      plant compounds suitable for drug discovery and development. Macromolecular
      docking studies provides most detailed possible view of drug-receptor interaction
      where the structure of drug is designed based on its fit to three dimensional
      structures of receptor site rather than by analogy to other active structures or
      random leads. Our previous studies indicate that Allicin sand Plumbagin could be
      used as the potent multi drug targets against the Neuraminidase, Hemagglutinin
      and M2 protein channel of influenza A (H1N1) pdm09. This in-vittro study has
      shown that P. indica L. and A. sativum extracts can inhibit influenza A
      (H1N1)pdm09 virus by inhibiting viral nucleoprotein synthesis and polymerase
      activity.

PMID- 27034601
TI  - UP1304, a Botanical Composition Containing Two Standardized Extracts of Curcuma
      longa and Morus alba, Mitigates Pain and Inflammation in Adjuvant-induced
      Arthritic Rats.
AB  - BACKGROUND: Though, the initial etiologies of arthritis are multifactorial,
      clinically, patients share pain as the prime complaints. Present day pain relief
      therapeutics heavily relies on the use of prescription and over the counter
      nonsteroidal anti-inflammatory drugs as the first line of defense where their
      long-term usage causes gastrointestinal and cardiovascular-related side effects.
      Hence, the need for evidence-based safer and efficacious alternatives from
      natural sources to overcome the most prominent and disabling symptoms of
      arthritis is an overdue. Here, we evaluated the anti-inflammatory and analgesic
      effect of UP1304, a composition that contains a standardized blend of two
      extracts from the rhizome of Curcuma longa and the root bark of Morus alba in
      adjuvant-induced arthritis models in rats. MATERIALS AND METHODS: The anti
      inflammatory and analgesic effects of the botanical composition were demonstrated
      in adjuvant-induced arthritis models in rats with oral dose ranges of 50-200
      mg/kg. Ibuprofen at a dose of 100 mg/kg was used as a reference compound. Ex vivo
      sulfated glycosaminoglycan inhibition assays were performed. RESULTS:
      Statistically significant improvements in pain resistance, suppression of paw
      edema and ankle thickness were observed in animals treated with UP1304 compared
      to vehicle-treated diseased rats. These results were similar to those achieved by
      ibuprofen treatment. Inhibitions of proteoglycan degradation were observed in a
      range of 37.5-61.7% for concentration of UP1304 at 50-200 MUg/mL when compared to
      interleukin-1alpha-exposed untreated explants. CONCLUSIONS: These data suggest
      that UP1304, for its analgesic and anti-inflammatory effects, could potentially
      be considered agent of botanical origin for the improvement of arthritis
      associated symptoms. SUMMARY: Pain is one of the cardinal signs of arthritis.Long
      term applications of commonly used non-steroidal anti-inflammatory drugs for pain
      relief are associated with cardiovascular and gastrointestinal side
      effects.Cartilage degradation evidenced as glycosaminoglycan loss from articular
      cartilage into the synovial fluid has been reported in arthritis
      patients.Adjuvant-induced arthritis model in rats are among the widely used
      models for efficacy evaluation of nutraceuticals.Efficacy of UP1304, a
      composition containing a blend of two standardized extracts from the rhizome of
      Curcuma longa and root bark of Morus alba, was evaluated in adjuvant-induced
      arthritis model in rats and in glycosaminoglycan releasing inhibition
      assays.UP1304 demonstrated its enhanced significance by improving the major
      cardinal signs of arthritis in vivo and ex vivo.UP1304 could potentially be
      considered as a dietary supplement product for the management of arthritis.

PMID- 27034602
TI  - Inhibition of Pro-inflammatory Mediators and Cytokines by Chlorella Vulgaris
      Extracts.
AB  - OBJECTIVE: The aim of this study was to determine the in vitro anti-inflammatory
      activities of solvent fractions from Chlorella vulgaris by inhibiting the
      production of pro-inflammatory mediators and cytokines. METHODS: Methanolic
      extracts (80%) of C. vulgaris were prepared and partitioned with solvents of
      increasing polarity viz., n-hexane, chloroform, ethanol, and water. Various
      concentrations of the fractions were tested for cytotoxicity in RAW 264.7 cells
      using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,
      and the concentrations inducing cell growth inhibition by about 50% (IC50) were
      chosen for further studies. Lipopolysaccharide (LPS) stimulated RAW 264.7 cells
      were treated with varying concentrations of C. vulgaris fractions and examined
      for its effects on nitric oxide (NO) production by Griess assay. The release of
      prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), and interleukin
      6 (IL-6) were quantified using enzyme-linked immunosorbent assay using Celecoxib
      and polymyxin B as positive controls. RESULTS: MTT assay revealed all the solvent
      fractions that inhibited cell growth in a dose-dependent manner. Of all the
      extracts, 80% methanolic extract exhibited the strongest anti-inflammatory
      activity by inhibiting NO production (P < 0.01), PGE2 (P < 0.05), TNF-alpha, and
      IL-6 (P < 0.001) release in LPS induced RAW 264.7 cells. Both hexane and
      chloroform fractions recorded a significant (P < 0.05) and dose-dependent
      inhibition of LPS induced inflammatory mediators and cytokines in vitro. The anti
      inflammatory effect of ethanol and aqueous extracts was not significant in the
      study. CONCLUSION: The significant inhibition of inflammatory mediators and
      cytokines by fractions from C. vulgaris suggests that this microalga would be a
      potential source of developing anti-inflammatory agents and a good alternate for
      conventional steroidal and nonsteroidal anti-inflammatory drugs. SUMMARY: C.
      vulgaris extracts have potential anti-inflammatory activitySolvent extraction
      using methanol, hexane, and chloroform has exhibited significant effect in LPS
      activated RAW 264.7 cellsC. vulgaris extracts reduce the production of NO, PGE2,
      TNF-alpha, and IL-6 in LPS activated RAW 264.7 cells. Abbreviations Used: COX-2:
      Cyclooxygenase-2, DMSO: Dimethyl sulfoxide, FBS: Fetal bovine serum, IL-6:
      Interleukin 6, iNOS: Inducible nitric oxide synthase, L-NMMA: NG-methyl-L
      arginine acetate salt, LPS: Lipopolysaccharide, MTT: 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide, NO: Nitric oxide, PBS: Phosphate buffered
      saline, PGE2: Prostaglandin E2, TNF-alpha: Tumor necrosis factor-alpha.

PMID- 27034603
TI  - Evaluation of In Vitro Cytotoxic and Antioxidant Activity of Datura metel Linn.
      and Cynodon dactylon Linn. Extracts.
AB  - AIM: To evaluate in vitro cytotoxicity and antioxidant activity of Datura metel
      L. and Cynodon dactylon L. extracts. MATERIALS AND METHODS: The extraction of
      plants parts (datura seed and fruit pulp) and areal parts of durva was carried
      out using soxhlet and cold extraction method using solvents namely methanol and
      distilled water. The total phenolic content (TPC) and total flavonoid content
      (TFC) was determined by established methods. The in vitro cytotoxicity assay was
      performed in vero cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay method. In vitro antioxidant activity of the
      extract was performed by 2, 2-diphenyl-1-picrylhydrazyl radical scavenging
      method. RESULTS: We found that the highest amount of TPC and TFC in methanolic
      extracts of seed (268.6 MUg of gallic acid equivalence/mg of dry plant material)
      and fruit pulp (8.84 MUg of quercetin equivalence/mg dry plant material) of D.
      metel, respectively prepared by Soxhlet method. The methanolic extract of C.
      dactylon prepared using soxhlation has shown potent free radical scavenging
      activity with 50% inhibitory concentration (IC50) value of 100 MUg/ml. The IC50
      of a methanolic cold extract of datura fruit was found to be 3 mg/ml against vero
      cell line. CONCLUSION: We observed that plant parts of C. dactylon and D. metel
      have a high antioxidant activity. Further research is needed to explore the
      therapeutic potential of these plant extracts. SUMMARY: In the present study we
      observed a positive correlation was between the phenolic and flavanoid content of
      the Datura metel and cynodon doctylon (durva) extracts with the free radical
      scavenging activities. Both were found to have a high antioxidant activity.
      Abbreviations used: BHA: Butylated hydroxyanisole, BHT: Butylated hydroxytoluene,
      CC50: 50% cell cytotoxic concentration, CNS: Central nervous system, DPPH: 2, 2
      diphenyl-1-picrylhydrazyl, IC50: 50% inhibitory concentration, MTT: 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), TFC: Total flavonoid
      content, TPC: Total phenolic content.

PMID- 27034604
TI  - Ethnobotanical Study of Latex Plants in the Maritime Region of Togo.
AB  - BACKGROUND: In Togo, a little is known about latex plants of the flora used for
      medicinal purposes. OBJECTIVE: The aim of this study was to identify the latex
      plant species and their medicinal uses in the Maritime Region of Togo. MATERIALS
      AND METHODS: The methodology was based on ethnobotanical semi-structural
      individual interviews of 220 informants. Quantitative ethnobotanical index was
      used to analyze the data. RESULTS: A total of 33 latex plants species were
      recorded, from 12 botanical families and 24 genera. The most represented families
      were Euphorbiaceae and Moraceae with eight species each. The relative importance
      (RI) value of each species and the informant consensus factor (ICF) of the
      ailments categories showed that Pergularia daemia (Forssk.) Chiov. (RI = 2.00)
      and Euphorbia hirta L. (RI = 1.91) were the most versatile in relation to their
      uses, and infectious diseases (ICF = 0.922) were the category with the greatest
      consensus among 17 categories. CONCLUSION: These latex plants of Togolese flora
      are variously used in traditional medicine and it would be important to undertake
      further investigations in phytochemistry, pharmacology, and toxicology to
      validate their uses. Abbreviations Used: UV: use value ICF: informant consensus
      factor RI: relative importance PP: pharmacological properties attributed to a
      species for a specific ailments AC: ailment categories treated by a given
      species.

PMID- 27034605
TI  - Lactoferrin from Camelus dromedarius Inhibits Nuclear Transcription Factor-kappa
      B Activation, Cyclooxygenase-2 Expression and Prostaglandin E2 Production in
      Stimulated Human Chondrocytes.
AB  - BACKGROUND: Osteoarthritis (OA) is a progressive joint disorder, which remains
      the leading cause of chronic disability in aged people. Nuclear factor-kappa B
      (NF)-kappaB is a major cellular event in OA and its activation by interleukin
      1beta (IL-1beta) plays a critical role in cartilage breakdown in these patients.
      OBJECTIVE: In this study, we examined the effect of lactoferrin on NF-kappaB
      activation, cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2)
      production in stimulated human articular chondrocytes. MATERIALS AND METHODS:
      Human chondrocytes were derived from OA articular cartilage and treated with
      camel lactoferrin and then stimulated with IL-1beta. Gene expression was
      determined by TaqMan assays and protein expression was studied by Western
      immunoblotting. NF-kappaB activity and PGE2 levels were determined by ELISA based
      assays. NF-kappaB activity was also determined by treatment of chondrocytes with
      NF-kappaB specific inhibitor Bay 11-7082. RESULTS: Lactoferrin inhibited IL-1beta
      induced activation and nuclear translocation of NF-kappaB p65 in human OA
      chondrocytes. Lactoferrin also inhibited mRNA/protein expression of COX-2 and
      production of PGE2. Moreover, Bay 11-7082 also inhibited IL-1beta-induced
      expression of COX-2 and production of PGE2. The inhibitory effect of lactoferrin
      on the IL-1beta induced expression of COX-2 or production of PGE2 was mediated at
      least in part via suppression of NF-kappaB activation. CONCLUSIONS: Our data
      determine camel lactoferrin as a novel inhibitor of IL-1beta-induced activation
      of NF-kappaB signaling events and production of cartilage-degrading molecule PGE2
      via inhibition of COX-2 expressions. These results may have important
      implications for the development of novel therapeutic strategies for the
      prevention/treatment of OA and other degenerative/inflammatory diseases. SUMMARY:
      Lactoferrin shows anti-arthritic activity in IL-1beta stimulated primary human
      chondrocytes.Lactoferrin inhibits IL-1beta-induced NF-kappaB
      activation.Lactoferrin inhibits production of cartilage degrading PGE2 via
      inhibition of COX-2 expression. Abbreviations Used: OA: Osteoarthritis IL-1beta:
      Interleukin-1 beta NF-kappaB: Nuclear factor-kappa B COX-2: cyclooxygenase-2
      PGE2: prostaglandin E2.

PMID- 27034606
TI  - Antimicrobial, Anti-inflammatory and Antioxidant Activities of Jatropha multifida
      L. (Euphorbiaceae).
AB  - BACKGROUND: Jatropha multifida is used in Togolease folk medicine for the healing
      of chronic wounds. OBJECTIVE: This study aims to investigate antibacterial, anti
      inflammatory and antioxidant activities of the leaves ethanolic extract.
      MATERIALS AND METHODS: The antimicrobial activity was assayed by National
      Committee for Clinical Laboratory Standards broth microdilution method on strains
      of Staphylococcus aureus and Pseudomoas aeruginosa isolated from wounds, whereas
      the anti-inflammatory activity was performed by carrageenan and histamine induced
      paw edema method in rat modele. The 2, 2-diphenyl-1picrylhydrazyl (DPPH) free
      radical scavenging and ferric reducing antioxidant power (FRAP) were used for the
      antioxidant activity. RESULTS: The antibacterial assay showed an in vitro growth
      inhibition of P. aeruginosa and S. aureus in dose-dependent manner, with minimum
      inhibitory concentration values ranging from 2.5 to 3.12 mg/mL for S. aureus and
      from 6.25 to 12.5 mg/mL for P. aeruginosa. The maximum paw anti-inflammatory
      effect occurred after 3 and 5 h administration of histamine and carrageenan,
      respectively. The DPPH radical scavenging and the FRAP assays yielded weak
      antioxidant activity. CONCLUSION: J. multifida possesses antibacterial and anti
      inflammatory activities that could justify the use of the plant for the treatment
      of wounds in the folk medicine. SUMMARY: Antibacterial on germs isolated from
      wound, anti-inflammatory and antioxidant activities of Jatropha multifida were
      assayed by NCCLS broth method, carrageenan and histamine, DPPH and FRAP
      respectively. The results indicated that Jatropha multifida possesses
      antibacterial and anti-inflammatory and weak antioxidant activities that could
      justify its use for the treatment of wounds in the folk medicine.

PMID- 27034607
TI  - Standardization of Unani Antidiabetic Tablet - Qurse Tabasheer.
AB  - BACKGROUND: Quality control of Unani polyherbal formulations is the need of the
      day for better acceptance of Unani medicine. Qurse Tabasheer (QT) is a Unani
      polyherbal formulation containing six ingredients, Tabasheer (Siliceous
      concretions) (Bambosa arundinaceae Retz.), Gule Surkh (Rosa damascena Mill.
      flower), Gulnar (Punica granatum Linn. flower), Tukhme kahu (Lactuca sativa Linn.
      seed), Tukhme khurfa (Portulaca oleraceae Linn. seed), and Gile Armani (bole)
      widely used in treatment of diabetes. The present study was taken up to
      scientifically evaluate the various physicochemical parameters to standardize the
      formulation. OBJECTIVE: To evaluate various physicochemical parameters including
      ash values, moisture content, extractive values, thin layer chromatography (TLC)
      and high-performance TLC (HPTLC), friability, disintegration, uniformity, and
      weight variation for standardization of QT. MATERIALS AND METHODS: Ingredients
      were identified by the experts. The method mentioned in national formulary of
      Unani Medicine with modification was followed for preparation of the tablets.
      Physicochemical standards were established for ideal batch of tablets on the
      basis of set parameters regarding friability, hardness, and disintegration.
      Various parameters such as organoleptic characters, extractive values for the
      extract and HPTLC fingerprinting postcompression were carried out for evaluation
      of QT. RESULTS: Parameters for loss of weight on drying, pH, ash values,
      extractive values documented. Qualitative chemical tests indicated the presence
      of alkaloid, glycoside, tannins, and steroids. TLC and HPTLC fingerprinting
      studies showing the presence of major peaks were documented. Friability,
      hardness, and disintegration time of ideal batch was 0.09 +/- 0.0057, 4.03 +/-
      0.087, and 25.57 +/- 0.4860 min, respectively, and it was found to be within the
      set limit. Weight variation was <5%. Total fungal and bacterial counts were found
      to be within the limit. CONCLUSION: Standards were established for poly herbal
      formulation QT, which may be used as reference for preparation and
      standardization of QT. SUMMARY: In this work Standardization of anti-diabetic
      tablet Qurse Tabasheer with diverse ingredients including herbal and mineral
      origin drugs has been attempted with identification of its ingredients,
      formulation, physicochemical evaluation and HPTLC finger printing, which may help
      in preparing consistent and better efficacious formulations. Abbreviations Used:
      QT: Qurse Tabasheer TLC: thin layer chromatography HPTLC: high-performance thin
      layer chromatography WHO: World health organization FRLHT: Foundation for
      Revitalization of Local Health Traditions Fe2O3: Iron oxide Sio2: Silica CaCo3:
      Calcium carbonate, Tio2: Titanium Oxide NIUM: National Institute of Unani
      Medicine #: Mesh size LOD: Loss of weight on drying USP: United state
      Pharmacopeia UV: Ultra Violet lambda: Lambda theta: theta CFU: Colony-forming
      unit.

PMID- 27034608
TI  - Gender Differences in the Developmental Links Between Conduct Problems and
      Depression Across Early Adolescence.
AB  - Various developmental models have attempted to explain the relationship between
      antisocial behavior and depressive symptoms in youth, often proposing
      intermediary processes such as social and academic functioning. However, few
      studies have tested these developmental models fully, particularly in mixed
      gender samples. The current study strives to fill this gap in the literature,
      examining these processes in an early adolescent sample. Results indicated both
      direct and indirect paths between antisocial behavior and depression. In
      addition, potentially important gender differences were found. These results
      underscore the importance of examining direct and indirect links between symptoms
      of depression and anti-social behavior, and suggest that there may be important
      developmental differences between girls and boys in the relationship between
      these symptoms.

PMID- 27034609
TI  - The Association Between Age and Ethics-Related Issues in Using Social Media for
      HIV Prevention in Peru.
AB  - Little research has focused on the ethical issues around using social media for
      HIV prevention in low- and middle-income countries (LMICs), such as Peru. This
      study surveyed participants from the HOPE social media HIV intervention HIV
      intervention in Peru to assess their experiences and perceptions of ethical
      issues in the study and the impact of age on their experiences and perceptions.
      This study found that, compared to younger participants, older participants were
      more likely to express higher levels of understanding of the consent form and
      trust that other participants were real. Older participants also reported being
      less likely to benefit in learning about their HIV status. Findings suggest that
      age plays a role in participants' experiences in a social media-based HIV
      intervention.

PMID- 27034610
TI  - An Adverse Family Environment During Adolescence Predicts Marijuana Use and
      Antisocial Personality Disorder in Adulthood.
AB  - Adult maladaptive behaviors including antisocial personality disorder (ASPD) and
      marijuana use are major public health concerns. At the present time, there is a
      dearth of research showing the interrelationships among the possible predictors
      of adult maladaptive behaviors (i.e., ASPD and marijuana use). Therefore, the
      current study examines the pathways from adverse family environments in late
      adolescence to these maladaptive behaviors in adulthood. There were 674
      participants (52 % African Americans, 48 % Puerto Ricans). Sixty percent of the
      sample was female. Structural equation modeling in the current study included 4
      waves of data collection (mean ages 19, 24, 29, and 36). An adverse family
      environment in late adolescence was related to greater externalizing personality
      in late adolescence, which in turn, was related to greater marijuana use in
      emerging adulthood. This in turn was positively associated with partner marijuana
      use in young adulthood, which in turn, was ultimately related to maladaptive
      behaviors in adulthood. An adverse family environment in late adolescence was
      also related to greater marijuana use in emerging adulthood, which in turn, was
      associated with an adverse relationship with one's partner in young adulthood.
      Such a negative partner relationship was related to maladaptive behaviors in
      adulthood. The findings suggest that family-focused interventions (Kumpfer and
      Alvarado in Am Psychol 58(6-7): 457-465, 2003) for dysfunctional families may be
      most helpful when they include the entire family.

PMID- 27034611
TI  - Experimental Study of Reciprocating Friction between Rape Stalk and Bionic
      Nonsmooth Surface Units.
AB  - Background. China is the largest producer of rape oilseed in the world; however,
      the mechanization level of rape harvest is relatively low, because rape materials
      easily adhere to the cleaning screens of combine harvesters, resulting in
      significant cleaning losses. Previous studies have shown that bionic nonsmooth
      surface cleaning screens restrain the adhesion of rape materials, but the
      underlying mechanisms remain unclear. Objective. The reciprocating friction
      between rape stalk and bionic nonsmooth metal surface was examined. Methods. The
      short-time Fourier transform method was used to discriminate the stable phase of
      friction signals and the stick-lag distance was defined to analyze the stable
      reciprocating friction in a phase diagram. Results. The reciprocating friction
      between rape stalk and metal surface is a typical stick-slip friction, and the
      bionic nonsmooth metal surfaces with concave or convex units reduced friction
      force with increasing reciprocating frequency. The results also showed that the
      stick-lag distance of convex surface increased with reciprocating frequency,
      which indicated that convex surface reduces friction force more efficiently.
      Conclusions. We suggest that bionic nonsmooth surface cleaning screens,
      especially with convex units, restrain the adhesion of rape materials more
      efficiently compared to the smooth surface cleaning screens. 

PMID- 27034612
TI  - A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered
      Tissue.
AB  - Tissue engineering is a multidisciplinary science based on the application of
      engineering approaches to biologic tissue formation. Engineered tissue internal
      organization represents a key aspect to increase biofunctionality before
      transplant and, as regarding skeletal muscles, the potential of generating
      contractile forces is dependent on the internal fiber organization and is
      reflected by some macroscopic parameters, such as the spontaneous contraction.
      Here we propose the application of digital image correlation (DIC) as an
      independent tool for an accurate and noninvasive measurement of engineered muscle
      tissue spontaneous contraction. To validate the proposed technique we referred to
      the X-MET, a promising 3-dimensional model of skeletal muscle. The images
      acquired through a high speed camera were correlated with a custom-made algorithm
      and the longitudinal strain predictions were employed for measuring the
      spontaneous contraction. The spontaneous contraction reference values were
      obtained by studying the force response. The relative error between the
      spontaneous contraction frequencies computed in both ways was always lower than
      0.15%. In conclusion, the use of a DIC based system allows for an accurate and
      noninvasive measurement of biological tissues' spontaneous contraction, in
      addition to the measurement of tissue strain field on any desired region of
      interest during electrical stimulation. 

PMID- 27034613
TI  - Optimized Prediction of Extreme Treatment Outcomes in Ovarian Cancer.
AB  - Ovarian cancer is the fifth leading cause of death among female cancers. Front
      line therapy for ovarian cancer is platinum-based chemotherapy. However, the
      response of patients is highly nonuniform. The TCGA database of serous ovarian
      carcinomas shows that ~10% of patients respond poorly to platinum-based
      chemotherapy, with tumors relapsing in seven months or less. Another 10% or so
      enjoy disease-free survival of three years or more. The objective of the present
      research is to identify a small number of highly predictive biomarkers that can
      distinguish between the two extreme responders and then extrapolate to all
      patients. This is achieved using the lone star algorithm that is specifically
      developed for biological applications. Using this algorithm, we are able to
      identify biomarker panels of 25 genes (of 12,000 genes) that can be used to
      classify patients into one of the three groups: super responders, medium
      responders, and nonresponders. We are also able to determine a discriminant
      function that can divide the entire patient population into two classes, such
      that one group has a clear survival advantage over the other. These biomarkers
      are developed using the TCGA Agilent platform data and cross-validated on the
      TCGA Affymetrix platform data, as well as entirely independent data from Tothill
      et al. The P-values on the training data are extremely small, sometimes below
      machine zero, while the P-values on cross-validation are well below the widely
      accepted threshold of 0.05. 

PMID- 27034614
TI  - Epiphyseal Sparing and Reconstruction by Frozen Bone Autograft after Malignant
      Bone Tumor Resection in Children.
AB  - Limb salvage surgery has become the standard treatment for malignant primary bone
      tumors in the extremities. Limb salvage represents a challenge in skeletally
      immature patients. Several treatment options are available for limb
      reconstruction after tumor resection in children. We report our results using the
      technique of epiphyseal sparing and reconstruction with frozen autograft bone in
      18 children. The mean follow-up period for the all patients included in this
      study is 72 +/- 26 m. Eight patients remained disease-free, seven patients lived
      with no evidence of disease, two were alive but with disease, and one patient
      died of the disease. Five- and ten-year rates of survival were 94.4%. Graft
      survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale
      was excellent in 17 patients (94.4%) and poor in one patient (5.5%).
      Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue
      recurrence, and leg length discrepancy in 7 cases. This technique is a good
      reconstructive choice in a child with a nonosteolytic primary or secondary bone
      tumor, responsive to chemotherapy, without involvement of the articular
      cartilage. It is a straight forward, effective, and biological technique, which
      affords immediate mobilization of joints and possible cryoimmune effects, with
      excellent long term functional outcome and less complication. 

PMID- 27034615
TI  - Spatial Supermarket Redlining and Neighborhood Vulnerability: A Case Study of
      Hartford, Connecticut.
AB  - The disinclination of chain supermarkets to locate or pull out existing stores
      from impoverished neighborhoods is termed as "supermarket redlining". This paper
      attempts to map and understand the spatial effects of potential supermarket
      redlining on food vulnerability in urban disadvantaged neighborhoods of Hartford,
      Connecticut. Using a combination of statistical and spatial analysis functions,
      we first, built a Supermarket Redlining Index (SuRI) from five indicators such as
      sales volume, employee count, accepts food coupons from federally assisted
      programs, and size and population density of the service area to rank
      supermarkets in the order of their importance. Second, to understand the effect
      of redlining, a Supermarket Redlining Impact Model (SuRIM) was built with eleven
      indicators describing both the socioeconomic and food access vulnerabilities. The
      interaction of these vulnerabilities would identify the final outcome:
      neighborhoods where the impact of supermarket redlining would be critical.
      Results mapped critical areas in the inner-city of Hartford where if a nearby
      supermarket closes or relocates to a suburb with limited mitigation efforts to
      gill the grocery gap, a large number of minority, poor, and disadvantaged
      residents will experience difficulties to access healthy food leading to food
      insecurity or perhaps a food desert. We also suggest mitigation efforts to reduce
      the impact of large supermarket closures.

PMID- 27034616
TI  - A systematic evaluation of the scale invariance of texture recognition methods.
AB  - A large variety of well-known scale-invariant texture recognition methods is
      tested with respect to their scale invariance. The scale invariance of these
      methods is estimated by comparing the results of two test setups. In the first
      test setup, the images of the training and evaluation set are acquired under same
      scale conditions and in the second test setup, the images in the evaluation set
      are gathered under different scale conditions than those of the training set. For
      the first test setup, scale invariance is not needed, whereas for the second test
      setup, scale invariance is obviously crucial. The difference between the results
      of these two test setups indicates the scale invariance of a method (the higher
      the scale invariance the lower the difference). The scale invariance of the
      methods is additionally estimated by analyzing the similarity of the feature
      vectors of images and their scaled versions. Additionally to the scale
      invariance, we also test eventual viewpoint and illumination invariance of the
      methods. As texture databases for our tests we use the KTH-TIPS database and the
      CUReT database. Results imply that many of the considered methods are not as
      scale-invariant as expected.

PMID- 27034617
TI  - The voltage gated Ca(2+)-channel Cav3.2 and therapeutic responses in breast
      cancer.
AB  - BACKGROUND: Understanding the cause of therapeutic resistance and identifying new
      biomarkers in breast cancer to predict therapeutic responses will help optimise
      patient care. Calcium (Ca(2+))-signalling is important in a variety of processes
      associated with tumour progression, including breast cancer cell migration and
      proliferation. Ca(2+)-signalling is also linked to the acquisition of multidrug
      resistance. This study aimed to assess the expression level of proteins involved
      in Ca(2+)-signalling in an in vitro model of trastuzumab-resistance and to assess
      the ability of identified targets to reverse resistance and/or act as potential
      biomarkers for prognosis or therapy outcome. METHODS: Expression levels of a
      panel of Ca(2+)-pumps, channels and channel regulators were assessed using RT
      qPCR in resistant and sensitive age-matched SKBR3 breast cancer cells,
      established through continuous culture in the absence or presence of trastuzumab.
      The role of Cav3.2 in the acquisition of trastuzumab-resistance was assessed
      through pharmacological inhibition and induced overexpression. Levels of Cav3.2
      were assessed in a panel of non-malignant and malignant breast cell lines using
      RT-qPCR and in patient samples representing different molecular subtypes (PAM50
      cohort). Patient survival was also assessed in samples stratified by Cav3.2
      expression (METABRIC and KM-Plotter cohort). RESULTS: Increased mRNA of Cav3.2
      was a feature of both acquired and intrinsic trastuzumab-resistant SKBR3 cells.
      However, pharmacological inhibition of Cav3.2 did not restore trastuzumab
      sensitivity nor did Cav3.2 overexpression induce the expression of markers
      associated with resistance, suggesting that Cav3.2 is not a driver of trastuzumab
      resistance. Cav3.2 levels were significantly higher in luminal A, luminal B and
      HER2-enriched subtypes compared to the basal subtype. High levels of Cav3.2 were
      associated with poor outcome in patients with oestrogen receptor positive (ER+)
      breast cancers, whereas Cav3.2 levels were correlated positively with patient
      survival after chemotherapy in patients with HER2-positive breast cancers.
      CONCLUSION: Our study identified elevated levels of Cav3.2 in trastuzumab
      resistant SKBR3 cell lines. Although not a regulator of trastuzumab-resistance in
      HER2-positive breast cancer cells, Cav3.2 may be a potential differential
      biomarker for survival and treatment response in specific breast cancer subtypes.
      These studies add to the complex and diverse role of Ca(2+)-signalling in breast
      cancer progression and treatment.

PMID- 27034618
TI  - Stress-induced endocytosis and degradation of epidermal growth factor receptor
      are two independent processes.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) is an important oncogenic
      protein in multiple types of cancer. Endocytosis and degradation of epidermal
      growth factor receptor (EGFR) are two key steps for down-regulation of cell
      surface level of EGFR and modulation of EGFR signaling. Stress conditions induce
      ligand-independent endocytosis and degradation of EGFR. However, it is not clear
      whether stress-induced endocytosis and degradation are consequential or two
      independent events. METHODS: Endocytosis and degradation of EGFR in response to
      stress treatment and effects of the p38 inhibitor, the Caspase-3 inhibitor and
      the proteasomal inhibitor in cervical cancer HeLa cells were determined using
      immunoblotting and immunofluorescent staining assays. RESULTS: Stress conditions,
      such as protein biosynthesis inhibition, UV light irradiation, and hyper-osmosis,
      induced both ligand-independent endocytosis and degradation of EGFR. Stress
      induced endocytosis of EGFR relies on p38 kinase activity, while stress-induced
      degradation of EGFR is catalyzed by Caspase-3 activity. Inhibiting p38 kinase
      impairs only the endocytosis but not the degradation, while inhibiting Caspase-3
      results in the opposite effect to inhibiting p38. Furthermore, proteasomal
      activity is required for stress-induced degradation of EGFR and cell death, but
      not for endocytosis. CONCLUSIONS: The results indicate that stress-induced
      endocytosis and degradation are two independent events and suggest stress
      signaling may utilize a double-secure mechanism to down-regulate cell surface
      EGFR in cancer cells.

PMID- 27034619
TI  - Investigation of proteome changes in osteoclastogenesis in low serum culture
      system using quantitative proteomics.
AB  - BACKGROUND: RAW 264.7 cells can differentiate into osteoclasts when cultured in
      medium supplemented with 1 % FBS. However, the proteomic changes in the
      development of RAW 264.7 cells into osteoclasts in low serum culture system have
      not been elucidated. Therefore, we conducted quantitative proteomics analysis to
      investigate proteomic changes during osteoclastogenesis in low serum culture
      system. RESULTS: Our study confirmed that mature multinucleated osteoclasts were
      generated in a low serum culture system, validated by upregulated expression of
      15 characteristic marker proteins, including TRAP, CTSK, MMP9, V-ATPase and
      ITGAV. Proteomics results demonstrated that 549 proteins expressed differentially
      in osteoclastogenesis in low serum culture system. In-depth bioinformatics
      analysis suggested that the differentially expressed proteins were mainly
      involved in mitochondrial activities and energy metabolism, including the
      electron transport chain pathway, TCA cycle pathway, mitochondrial LC-fatty acid
      beta-oxidation pathway and fatty acid biosynthesis pathway. The data have been
      deposited to the ProteomeXchange with identifier PXD001935. CONCLUSION:
      Osteoclast formation is an ATP consuming procedure, whether occurring in a low
      serum culture system or a conventional culture system. In contrast to osteoclasts
      formed in conventional culture system, the fatty acid biosynthesis pathway was
      upregulated in osteoclasts cultured in low serum condition.

PMID- 27034621
TI  - Everyday problems with executive dysfunction and impulsivity in adults recovering
      from methamphetamine addiction.
AB  - OBJECTIVES: Compared with non-addicted controls (CTLs), adults in remission from
      methamphetamine addiction (MA-REM) evidence impairments on objective measures of
      executive functioning and impulsivity. METHODS: To evaluate the impact of these
      impairments in MA-REM adults, demographically matched groups (MA-REM, n=30; CTLs,
      n=24) completed objective and self-report measures of executive functioning and
      impulsivity. RESULTS: MA-REM adults demonstrated significantly (p < 0.050)
      greater objective and subjective problems with executive functioning and
      impulsivity. CONCLUSIONS: These results suggest that adults in MA-REM are aware
      of their deficits and that these deficits have significant impact in everyday
      life.

PMID- 27034622
TI  - Family Functioning as a Mediator of Relations between Family History of Substance
      Use Disorder and Impulsivity.
AB  - : Impulsivity is strongly related to the development of adolescent substance use.
      Therefore, understanding factors that influence impulsive characteristics is
      important for the development of prevention and intervention programs.
      Intervention and prevention programs focused on factors that influence impulsive
      characteristics are especially important for those at particularly high risk for
      the expression of impulsivity - those with a family history of substance use
      disorder. A factor of particular interest is family functioning. AIM: To examine
      family functioning as a mediator of relations between having a family history of
      substance use disorder and impulsivity. METHODS: Participants included a majority
      Hispanic sample of pre-adolescent boys and girls (mean age 10.99, SD = .84)
      recruited from the community who did (FH+) and did not (FH-) have a family
      history of substance use disorder. FH status and the quality of family
      functioning were compared at the initial visit with impulsiveness assessed a year
      later. RESULTS: Results showed FH+ children had worse family functioning; worse
      family functioning was related to higher levels of impulsivity, and higher levels
      of impulsivity among FH+ children were due to the influence of family functioning
      on levels of impulsivity. In other words, family functioning mediated relations
      between having a family history of substance use disorder and impulsivity.
      CONCLUSION: These results indicate that higher levels of impulsivity in FH+
      children are due in part to worse family functioning.

PMID- 27034623
TI  - Acute and chronic safety and efficacy of dose dependent creatine nitrate
      supplementation and exercise performance.
AB  - BACKGROUND: Creatine monohydrate (CrM) and nitrate are popular supplements for
      improving exercise performance; yet have not been investigated in combination. We
      performed two studies to determine the safety and exercise performance
      characteristics of creatine nitrate (CrN) supplementation. METHODS: Study 1
      participants (N = 13) ingested 1.5 g CrN (CrN-Low), 3 g CrN (CrN-High), 5 g CrM
      or a placebo in a randomized, crossover study (7d washout) to determine
      supplement safety (hepatorenal and muscle enzymes, heart rate, blood pressure and
      side effects) measured at time-0 (unsupplemented), 30-min, and then hourly for 5
      h post-ingestion. Study 2 participants (N = 48) received the same CrN treatments
      vs. 3 g CrM in a randomized, double-blind, 28d trial inclusive of a 7-d interim
      testing period and loading sequence (4 servings/d). Day-7 and d-28 measured
      TendoTM bench press performance, Wingate testing and a 6x6-s bicycle ergometer
      sprint. Data were analyzed using a GLM and results are reported as mean +/- SD or
      mean change +/- 95 % CI. RESULTS: In both studies we observed several
      significant, yet stochastic changes in blood markers that were not indicative of
      potential harm or consistent for any treatment group. Equally, all treatment
      groups reported a similar number of minimal side effects. In Study 2, there was a
      significant increase in plasma nitrates for both CrN groups by d-7, subsequently
      abating by d-28. Muscle creatine increased significantly by d-7 in the CrM and
      CrN-High groups, but then decreased by d-28 for CrN-High. By d-28, there were
      significant increases in bench press lifting volume (kg) for all groups (PLA,
      126.6, 95 % CI 26.3, 226.8; CrM, 194.1, 95 % CI 89.0, 299.2; CrN-Low, 118.3, 95 %
      CI 26.1, 210.5; CrN-High, 267.2, 95 % CI 175.0, 359.4, kg). Only the CrN-High
      group was significantly greater than PLA (p < 0.05). Similar findings were
      observed for bench press peak power (PLA, 59.0, 95 % CI 4.5, 113.4; CrM, 68.6, 95
      % CI 11.4, 125.8; CrN-Low, 40.9, 95 % CI -9.2, 91.0; CrN-High, 60.9, 95 % CI
      10.8, 111.1, W) and average power. CONCLUSIONS: Creatine nitrate delivered at 3 g
      was well-tolerated, demonstrated similar performance benefits to 3 g CrM, in
      addition, within the confines of this study, there were no safety concerns.

PMID- 27034625
TI  - Mining Multi-Aspect Reflection of News Events in Twitter: Discovery, Linking and
      Presentation.
AB  - A major event often has repercussions on both news media and microblogging sites
      such as Twitter. Reports from mainstream news agencies and discussions from
      Twitter complement each other to form a complete picture. An event can have
      multiple aspects (sub-events) describing it from multiple angles, each of which
      attracts opinions/comments posted on Twitter. Mining such reflections is
      interesting to both policy makers and ordinary people seeking information. In
      this paper, we propose a unified framework to mine multi-aspect reflections of
      news events in Twitter. We propose a novel and efficient dynamic hierarchical
      entity-aware event discovery model to learn news events and their multiple
      aspects. The aspects of an event are linked to their reflections in Twitter by a
      bootstrapped dataless classification scheme, which elegantly handles the
      challenges of selecting informative tweets under overwhelming noise and bridging
      the vocabularies of news and tweets. In addition, we demonstrate that our
      framework naturally generates an informative presentation of each event with
      entity graphs, time spans, news summaries and tweet highlights to facilitate user
      digestion.

PMID- 27034624
TI  - The effects of a single-dose thermogenic supplement on resting metabolic rate and
      hemodynamic variables in healthy females--a randomized, double-blind, placebo
      controlled, cross-over trial.
AB  - BACKGROUND: Recent investigations have identified that commercially available
      dietary supplements, containing a combination of thermogenic ingredients, can
      increase resting metabolic rate (RMR). Thermogenic dietary supplements can have a
      positive influence on RMR, but the magnitude can vary based on the active
      ingredient and/or combination of active ingredients. Additionally, further safety
      evaluation is needed on multi-ingredient supplements that contain caffeine, due
      to its potential effect on heart rate (HR) and blood pressure (BP). The purpose
      of this study was to examine the effects of a commercially available dietary
      supplement on RMR and hemodynamic variables in healthy females. METHODS: 13
      female participants (26.1 +/- 11.3 years; 163.4 +/- 9.1 cm; 63.7 +/- 8.0 kg, and
      24 +/- 5 BMI) volunteered to participate in this investigation. Participants
      underwent two testing sessions separated by approximately 7 days. On their first
      visit, participants arrived to the laboratory after an overnight fast and
      underwent a baseline RMR, HR, and BP assessment. Next, each participant ingested
      a thermogenic dietary supplement or placebo and repeated the RMR, HR, and BP
      assessments at 60, 120, and 180-minutes post-ingestion. Approximately 1-week
      later, the alternative supplement was ingested and the assessments were repeated
      in the exact same manner. Data were analyzed via a 2-factor [2x4] within-subjects
      repeated measures analysis of variance (ANOVA). Post-hoc tests were analyzed via
      paired samples t-tests. RESULTS: Repeated measures ANOVA revealed a significant
      effect for time relative to raw RMR data. Post-hoc analysis revealed that the
      dietary supplement treatment significantly increased RMR at 60-minutes, 120
      minutes, and 180-minutes post ingestion (p < 0.05) as compared to baseline RMR
      values. No changes in RMR were observed for the placebo treatment (p > 0.05).
      Heart rate was not significantly affected at any time point with either
      supplement; however, main effects of treatment and time were observed for both
      systolic and diastolic blood pressure (p < 0.05). CONCLUSIONS: The thermogenic
      dietary supplement treatment experienced greater elevations in RMR as compared to
      baseline. Due to the slight elevations in blood pressure, caution should be taken
      for those with increased risk for hypertension or pre-hypertension. Taken on a
      daily basis, thermogenic dietary supplementation may increase overall energy
      expenditure, potentially leading to reductions in fat mass over time.

PMID- 27034626
TI  - KnowSim: A Document Similarity Measure on Structured Heterogeneous Information
      Networks.
AB  - As a fundamental task, document similarity measure has broad impact to document
      based classification, clustering and ranking. Traditional approaches represent
      documents as bag-of-words and compute document similarities using measures like
      cosine, Jaccard, and dice. However, entity phrases rather than single words in
      documents can be critical for evaluating document relatedness. Moreover, types of
      entities and links between entities/words are also informative. We propose a
      method to represent a document as a typed heterogeneous information network
      (HIN), where the entities and relations are annotated with types. Multiple
      documents can be linked by the words and entities in the HIN. Consequently, we
      convert the document similarity problem to a graph distance problem. Intuitively,
      there could be multiple paths between a pair of documents. We propose to use the
      meta-path defined in HIN to compute distance between documents. Instead of
      burdening user to define meaningful meta-paths, an automatic method is proposed
      to rank the meta-paths. Given the meta-paths associated with ranking scores, an
      HIN-based similarity measure, KnowSim, is proposed to compute document
      similarities. Using Freebase, a well-known world knowledge base, to conduct
      semantic parsing and construct HIN for documents, our experiments on 20Newsgroups
      and RCV1 datasets show that KnowSim generates impressive high-quality document
      clustering.

PMID- 27034627
TI  - Formation of Silver Nanoclusters from a DNA Template Containing Ag(I)-Mediated
      Base Pairs.
AB  - A series of DNA double helices containing different numbers of silver(I)-mediated
      base pairs involving the artificial nucleobases imidazole or 2-methylimidazole
      has been applied for the generation of DNA-templated silver nanoclusters. The
      original Ag(I)-containing nucleic acids as well as the resulting nanoclusters and
      nanoparticles have been characterized by means of UV/Vis spectroscopy, circular
      dichroism (CD) spectroscopy, fluorescence spectroscopy, and transmission electron
      microscopy (TEM). The results show for the first time that metal-mediated base
      pairs can be used for the templated growth of metal nanoclusters. 

PMID- 27034628
TI  - Brands matter: Major findings from the Alcohol Brand Research Among Underage
      Drinkers (ABRAND) project.
AB  - BACKGROUND: Alcohol research focused on underage drinkers has not comprehensively
      assessed the landscape of brand-level drinking behaviors among youth. This
      information is needed to profile youth alcohol use accurately, explore its
      antecedents, and develop appropriate interventions. METHODS: We collected
      national data on the alcohol brand-level consumption of underage drinkers in the
      United States and then examined the association between those preferences and
      several factors including youth exposure to brand-specific alcohol advertising,
      corporate sponsorships, popular music lyrics, and social networking sites, and
      alcohol pricing. This paper summarizes our findings, plus the results of other
      published studies on alcohol branding and youth drinking. RESULTS: Our findings
      revealed several interesting facts regarding youth drinking. For example, we
      found that: 1) youth are not drinking the cheapest alcohol brands; 2) youth brand
      preferences differ from those of adult drinkers; 3) underage drinkers are not
      opportunistic in their alcohol consumption, but instead consume a very specific
      set of brands; 4) the brands that youth are heavily exposed to in magazines and
      television advertising correspond to the brands they most often report consuming;
      and 5) youth consume more of the alcohol brands to whose advertising they are
      most heavily exposed. CONCLUSION: The findings presented here suggests that brand
      level alcohol research will provide important insight into youth drinking
      behaviors, the factors that contribute to youth alcohol consumption, and
      potential avenues for effective public health surveillance and programming.

PMID- 27034629
TI  - Impact of Wikipedia on citation trends.
AB  - It has been suggested that the "visibility" of an article influences its citation
      count. More specifically, it is believed that the social media can influence
      article citations.Here we tested the hypothesis that inclusion of scholarly
      references in Wikipedia affects the citation trends. To perform this analysis, we
      introduced a citation "propensity" measure, which is inspired by the concept of
      amino acid propensity for protein secondary structures. We show that although
      citation counts generally increase during time, the citation "propensity" does
      not increase after inclusion of a reference in Wikipedia. 

PMID- 27034630
TI  - Influence of framing on medical decision making.
AB  - Numerous studies have demonstrated the robustness of the framing effect in a
      variety of contexts, especially in medical decision making. Unfortunately,
      research is still inconsistent as to how so many variables impact framing effects
      in medical decision making. Additionally, much attention should be paid to the
      framing effect not only in hypothetical scenarios but also in clinical
      experience. 

PMID- 27034631
TI  - Relevance of genetic disposition versus environmental exposure for cancer risk:
      an old controversy revisited with novel methods.

PMID- 27034632
TI  - Hepatotoxicity induced by zoledronic acid in an aged woman with primary
      osteoporosis.
AB  - Zoledronic acid, a bisphosphonate, has been approved for treatment and prevention
      of osteoporosis. This case describes a 73-year-old woman with primary
      osteoporosis who developed transient hepatotoxicity after zoledronic acid (ZOL)
      treatment. Three days after ZOL infusion, aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were
      increased by 9.9, 8.1, and 3.7 times, respectively, compared with pretreatment
      values. Liver protective agents were administered. The aminotransferase returned
      within normal ranges 12 days post-infusion. Currently, the relationship of ZOL
      and liver damage is not quite clear, which cannot be explained by its
      pharmacokinetics. The aim of this case report is to increase the clinician's
      awareness of the possible adverse effect on the liver, and ZOL should be
      cautiously administered in patients with liver disease. 

PMID- 27034633
TI  - Familial pattern of large vestibular aqueduct syndrome in a Chinese family.
AB  - Large Vestibular Aqueduct Syndrome (LVAS) is the most common radiographic
      malformation in children with early onset of hearing loss. Usually its occurrence
      is non-familial, however intriguingly a portion of patients with LVAS is found to
      have evidence of genetic predisposition. We described cases of LVAS in two
      siblings of a Chinese family. The elder sister first presented with reduced
      hearing since childhood and her brother has a similar complaint upon further
      questioning. Their hearing test showed bilateral sensorineural hearing loss
      (SNHL) and computed tomography (CT) of temporal bone showed enlarged vestibular
      aqueduct in both patients. We described an approach to diagnosis of LVAS and
      highlight the importance of hearing assessment in genetic link hearing loss. 

PMID- 27034634
TI  - Recent studies on flavonoids and their antioxidant activities.

PMID- 27034635
TI  - Osteoporosis awareness among primary care physicians in Malaysia.

PMID- 27034636
TI  - Neuroprotective effects of medicinal plants.

PMID- 27034637
TI  - Interaction of genetic variants towards increased cancer risk.

PMID- 27034638
TI  - Advances in 2D and 3D in vitro systems for hepatotoxicity testing.

PMID- 27034639
TI  - Pseudomonas aeruginosa bacteremia secondary to acute right leg cellulitis: case
      of community-acquired infection.
AB  - Pseudomonas aeruginosa is a gram-negative bacillus that causes wide spectrum
      clinical infections. However, it is most frequently associated with hospital
      acquired infection. In this case a 58-year-old male with underlying hypertension
      and dyslipidaemia was admitted for acute right leg cellulitis. Pseudomonas
      aeruginosa was identified from the case, though it was not a usual suspected
      organism. It might be due to community-acquired infection. 

PMID- 27034640
TI  - Highlight report: Functional consequences of urinary bladder cancer risk
      variants.

PMID- 27034641
TI  - Improved genotyping of N-acetyltransferase 2: role of the ultra-slow acetylators.

PMID- 27034642
TI  - In vitro test systems and their limitations.

PMID- 27034643
TI  - Transcriptomics in developmental toxicity testing.

PMID- 27034644
TI  - Working conditions as predictors of retirement intentions and exit from paid
      employment: a 10-year follow-up of the English Longitudinal Study of Ageing.
AB  - Population ageing in Western countries has made delayed retirement and extended
      working life a policy priority in recent years. Retirement timing has been linked
      to individual factors such as health and wealth, but less is known about the role
      of the psychosocial work environment. This paper drew upon longitudinal data on
      3462 workers aged 50-69 from five waves of the English Longitudinal Study of
      Ageing (ELSA). Regression models were used to assess the association of working
      conditions with preferred timing of retirement and actual work exit. Adjusting
      for a range of covariates, job demands (aspects of the job requiring sustained
      physical or psychological effort) were associated with preferences for earlier
      retirement (by 0.18 years; 95 % C.I. 0.06, 0.31). Decision authority was
      associated with preferences for later retirement (by 0.38 years; 95 % C.I. 0.23,
      0.53) and reduced odds of work exit (OR = 0.93; 95 % C.I. 0.88, 0.97). Low
      recognition at work was associated with increased odds of work exit (OR = 1.23;
      95 % C.I. 1.10, 1.43). There was little evidence of any interactive relationship
      between demands and resources. Efforts to extend working life should address
      issues relating to the immediate psychosocial work environment. Providing older
      workers with increased sense of control, and ensuring contributions are
      adequately recognised, may delay retirement intentions and the timing of labour
      market exit.

PMID- 27034646
TI  - Travel behaviour change in old age: the role of critical incidents in public
      transport.
AB  - Older people's travel behaviour is affected by negative or positive critical
      incidents in the public transport environment. With the objective of identifying
      such incidents during whole trips and examining how travel behaviour had changed,
      we have conducted in-depth interviews with 30 participants aged 65-91 years in
      the County of Stockholm, Sweden. Out of 469 incidents identified, 77 were
      reported to have resulted in travel behaviour change, 67 of them in a negative
      way. Most critical incidents were encountered in the physical environment on
      board vehicles and at stations/stops as well as in pricing/ticketing. The
      findings show that more personal assistance, better driving behaviour, and swift
      maintenance of elevators and escalators are key facilitators that would improve
      predictability in travelling and enhance vulnerable older travellers' feeling of
      security. The results demonstrate the benefit of involving different groups of
      end users in future planning and design, such that transport systems would meet
      the various needs of its end users.

PMID- 27034645
TI  - Is cognitive lifestyle associated with depressive thoughts and self-reported
      depressive symptoms in later life?
AB  - Key components of cognitive lifestyle are educational attainment, occupational
      complexity and engagement in cognitively stimulating leisure activities. Each of
      these factors is associated with experiencing fewer depressive symptoms in later
      life, but no study to date has examined the relationship between overall
      cognitive lifestyle and depressive symptoms. This task is made more complex
      because relatively few older participants in cross-sectional studies will be
      currently experiencing depression. However, many more will show evidence of a
      depressive thinking style that predisposes them towards depression. This study
      aimed to investigate the extent to which cognitive lifestyle and its individual
      components are associated with depressive thoughts and symptoms. Two hundred and
      six community-dwelling participants aged 65+ completed the depressive cognitions
      scale, the geriatric depression scale and the lifetime of experiences
      questionnaire, which assesses cognitive lifestyle. Correlational analysis
      indicated that each of the individual lifestyle factors-education, occupational
      complexity and activities in young adulthood, mid-life and later life-and the
      combined cognitive lifestyle score was positively associated with each other and
      negatively with depressive symptoms, while all except education were negatively
      associated with depressive thoughts. Depressive thoughts and symptoms were
      strongly correlated. Cognitive lifestyle score explained 4.6 % of the variance in
      depressive thoughts and 10.2 % of the variance in depressive symptoms. The
      association of greater participation in cognitive activities, especially in later
      life, with fewer depressive symptoms and thoughts suggests that preventive
      interventions aimed at increasing participation in cognitively stimulating
      leisure activity could be beneficial in decreasing the risk of experiencing
      depressive thoughts and symptoms in later life.

PMID- 27034647
TI  - Prevalence and correlates of tobacco use among adolescents in the schools of
      Kalaiya, Nepal: a cross-sectional questionnaire based study.
AB  - BACKGROUND: Adolescent students are vulnerable group for tobacco addiction.
      Tobacco use among school children is becoming a serious problem in developing
      countries. This study was carried out to estimate the prevalence of tobacco use
      and to determine associated factors among adolescent students of Kalaiya
      municipality. METHODS: A cross sectional survey was carried out by self
      administered questionnaire adapted from Global Youth Tobacco Survey to assess
      tobacco use among the representative sample of 1540 adolescent students selected
      by stratified random sampling from December 2014 to May 2015. RESULT: Overall
      prevalence of 'ever users' of tobacco products was 25.3 %. Prevalence among boys
      and girls was 31 and 14.4 % respectively. Mean age at initiation of using tobacco
      was 13.38 +/- 1.62 years. The correlates of tobacco use were: sex, ethnicity,
      family members and friends using tobacco products, and students exposed at home
      and public place. CONCLUSION: School based interventions and tobacco education
      are necessary to prevent initiation and cessation of tobacco use. Legislations
      related to tobacco control should be enforced to decrease availability,
      accessibility and affordability of tobacco products. Social norms of tobacco use
      among parents and others at home as well as at public place should be modified to
      curb the tobacco use among school students.

PMID- 27034648
TI  - Detection of Cardiac Function Abnormality from MRI Images Using Normalized Wall
      Thickness Temporal Patterns.
AB  - Purpose. To develop a method for identifying abnormal myocardial function based
      on studying the normalized wall motion pattern during the cardiac cycle. Methods.
      The temporal pattern of the normalized myocardial wall thickness is used as a
      feature vector to assess the cardiac wall motion abnormality. Principal component
      analysis is used to reduce the feature dimensionality and the maximum likelihood
      method is used to differentiate between normal and abnormal features. The
      proposed method was applied on a dataset of 27 cases from normal subjects and
      patients. Results. The developed method achieved 81.5%, 85%, and 88.5% accuracy
      for identifying abnormal contractility in the basal, midventricular, and apical
      slices, respectively. Conclusions. A novel feature vector, namely, the normalized
      wall thickness, has been introduced for detecting myocardial regional wall motion
      abnormality. The proposed method provides assessment of the regional myocardial
      contractility for each cardiac segment and slice; therefore, it could be a
      valuable tool for automatic and fast determination of regional wall motion
      abnormality from conventional cine MRI images. 

PMID- 27034650
TI  - List-Based Simulated Annealing Algorithm for Traveling Salesman Problem.
AB  - Simulated annealing (SA) algorithm is a popular intelligent optimization
      algorithm which has been successfully applied in many fields. Parameters' setting
      is a key factor for its performance, but it is also a tedious work. To simplify
      parameters setting, we present a list-based simulated annealing (LBSA) algorithm
      to solve traveling salesman problem (TSP). LBSA algorithm uses a novel list-based
      cooling schedule to control the decrease of temperature. Specifically, a list of
      temperatures is created first, and then the maximum temperature in list is used
      by Metropolis acceptance criterion to decide whether to accept a candidate
      solution. The temperature list is adapted iteratively according to the topology
      of the solution space of the problem. The effectiveness and the parameter
      sensitivity of the list-based cooling schedule are illustrated through benchmark
      TSP problems. The LBSA algorithm, whose performance is robust on a wide range of
      parameter values, shows competitive performance compared with some other state-of
      the-art algorithms. 

PMID- 27034651
TI  - Exploring the Combination of Dempster-Shafer Theory and Neural Network for
      Predicting Trust and Distrust.
AB  - In social media, trust and distrust among users are important factors in helping
      users make decisions, dissect information, and receive recommendations. However,
      the sparsity and imbalance of social relations bring great difficulties and
      challenges in predicting trust and distrust. Meanwhile, there are numerous
      inducing factors to determine trust and distrust relations. The relationship
      among inducing factors may be dependency, independence, and conflicting. Dempster
      Shafer theory and neural network are effective and efficient strategies to deal
      with these difficulties and challenges. In this paper, we study trust and
      distrust prediction based on the combination of Dempster-Shafer theory and neural
      network. We firstly analyze the inducing factors about trust and distrust,
      namely, homophily, status theory, and emotion tendency. Then, we quantify
      inducing factors of trust and distrust, take these features as evidences, and
      construct evidence prototype as input nodes of multilayer neural network.
      Finally, we propose a framework of predicting trust and distrust which uses
      multilayer neural network to model the implementing process of Dempster-Shafer
      theory in different hidden layers, aiming to overcome the disadvantage of
      Dempster-Shafer theory without optimization method. Experimental results on a
      real-world dataset demonstrate the effectiveness of the proposed framework. 

PMID- 27034652
TI  - Bioinspired Coordinated Path Following for Vessels with Speed Saturation Based on
      Virtual Leader.
AB  - This paper investigates the coordinated path following of multiple marine vessels
      with speed saturation. Based on virtual leader strategy, the authors show how the
      neural dynamic model and passivity-based techniques are brought together to yield
      a distributed control strategy. The desired path following is achieved by means
      of a virtual dynamic leader, whose controller is designed based on the biological
      neural shunting model. Utilizing the characteristic of bounded and smooth output
      of neural dynamic model, the tracking error jump is avoided and speed saturation
      problem is solved in straight path. Meanwhile, the coordinated path following of
      multiple vessels with a desired spatial formation is achieved through defining
      the formation reference point. The consensus of formation reference point is
      realized by using the synchronization controller based on passivity. Finally,
      simulation results validate the effectiveness of the proposed coordinated
      algorithm. 

PMID- 27034649
TI  - PPARalpha Agonist Fenofibrate Reduced the Secreting Load of beta-Cells in
      Hypertriglyceridemia Patients with Normal Glucose Tolerance.
AB  - Hypertriglyceridemia is an important risk factor associated with insulin
      resistance and beta-cell dysfunction. This study investigated the effects of
      hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and beta
      cell function in subjects with normal glucose tolerance. A total of 1974 subjects
      with normal glucose tolerance were divided into the normal TG group (NTG group, n
      = 1302) and hypertriglyceridemia group (HTG group, n = 672). Next, 92 patients
      selected randomly from 672 patients with hypertriglyceridemia were assigned to a
      24-week fenofibrate treatment. The HTG group had increased waist circumference
      (WC), body mass index (BMI), homeostasis model assessment of insulin resistance
      (HOMA-IR), and homeostasis model assessment of beta-cell function (HOMA-beta) and
      decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG
      group (all P < 0.01). The 24-week fenofibrate treatment significantly decreased
      the WC, BMI, TG, HOMA-IR, and HOMA-beta levels and increased the HDL-C levels in
      the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR: P < 0.05; TG, HDL
      C, and HOMA-beta: P < 0.01). The fenofibrate treatment significantly alleviated
      insulin resistance and reduced the secreting load of beta-cells in the
      hypertriglyceridemia patients with normal glucose tolerance. 

PMID- 27034653
TI  - Low Cost Eye Tracking: The Current Panorama.
AB  - Despite the availability of accurate, commercial gaze tracker devices working
      with infrared (IR) technology, visible light gaze tracking constitutes an
      interesting alternative by allowing scalability and removing hardware
      requirements. Over the last years, this field has seen examples of research
      showing performance comparable to the IR alternatives. In this work, we survey
      the previous work on remote, visible light gaze trackers and analyze the explored
      techniques from various perspectives such as calibration strategies, head pose
      invariance, and gaze estimation techniques. We also provide information on
      related aspects of research such as public datasets to test against, open source
      projects to build upon, and gaze tracking services to directly use in
      applications. With all this information, we aim to provide the contemporary and
      future researchers with a map detailing previously explored ideas and the
      required tools. 

PMID- 27034655
TI  - Response to Pegylated Interferon Plus Ribavirin in Patients with Hepatitis C
      Virus Genotype 6a Infection from Guangdong and Guangxi Province of China.
AB  - Aim. Our aim is to survey the treatment effect of PEG-IFN plus ribavirin in
      patients infected with HCV genotype 6a in Guangdong and Guangxi province of China
      and investigate best course of antiviral treatment for patients with HCV-6a
      infection. Methods. 515 eligible patients received subcutaneous 180 MUg PEG
      IFNalpha-2a or 1.5 MUg/kg PEG-IFNalpha-2b once weekly plus oral ribavirin.
      Primary outcome was SVR by intention-to-treat analysis. Secondary outcome was
      RVR, cEVR, ETR, and relapse rate. Results. SVR in patients with HCV-6a infection
      treated for 48 weeks was comparable to that in patients with HCV-2/3 infection
      (80.9% versus 82.5%, p = 0.812) and higher than that in patients with HCV-1b
      infection (80.9% versus 67.2%, p = 0.014). ETR (98.9% versus 90.6%, p = 0.016),
      virological response at month 3 of end-of- treatment (88.8% versus 76.6%, p =
      0.044), SVR (80.9% versus 65.6%, p = 0.032), and virological response at month 12
      of end-of-treatment (76.4% versus 60.9%, p = 0.04) in patients with HCV-6a
      infection treated for 48 weeks were higher than those in patients with HCV-6a
      infection treated for 24 weeks. Conclusion. SVR in patients with HCV-6a treated
      for 48 weeks was comparable to that in patients with HCV-2/3 infection and higher
      than that in patients with HCV-1b infection; patients with HCV-6a infection
      treated for 48 weeks had a superior treatment response than patients treated for
      24 weeks. 

PMID- 27034656
TI  - Clinical Outcome of Eradication Therapy for Gastric Mucosa-Associated Lymphoid
      Tissue Lymphoma according to H. pylori Infection Status.
AB  - Background. To evaluate the long-term outcome of H. pylori eradication therapy
      for gastric MALT lymphoma according to the presence of H. pylori infection.
      Methods. We retrospectively reviewed the medical records of patients between
      January 2001 and June 2014. The clinicopathologic characteristics and clinical
      outcomes were compared between H. pylori-positive and H. pylori-negative gastric
      MALT lymphoma groups. Results. Fifty-four patients were enrolled: 12 H. pylori
      negative and 42 H. pylori-positive patients. The tumor was located more
      frequently in both the proximal and distal parts of the stomach (P = 0.001), and
      the percentage of multiple lesions was significantly greater in the H. pylori
      negative group (P = 0.046). Forty-seven patients received initial eradication
      therapy, and 85% (35/41) of H. pylori-positive patients and 50% (3/6) of H.
      pylori-negative patients achieved complete remission after eradication therapy.
      The presence of multiple lesions was a predictive factor for unresponsiveness to
      H. pylori eradication (P = 0.024). The efficacy of eradication therapy (P =
      0.133), complete remission (CR) maintenance period, and relapse after eradication
      therapy were not significantly different between the two groups. Conclusions. H.
      pylori eradication therapy could be an effective first-line treatment for
      localized H. pylori-negative gastric MALT lymphoma, especially for single
      lesions. 

PMID- 27034654
TI  - Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their
      Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of
      inflammatory bowel diseases (IBD). The aim of our study was to evaluate the
      expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and
      Crohn's disease. The study group comprised 34 patients with UC and 10 patients
      with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in
      tissue samples was performed using immunohistochemistry. The overexpression of
      MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory
      infiltration in UC patients. In contrast, in CD subjects the positive expression
      of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2
      expression was in inflammatory infiltration. Metalloproteinases' expression was
      associated with the presence of erosions, architectural tissue changes, and
      inflammatory infiltration in the lamina propria of UC patients. The expression of
      metalloproteinase inhibitors correlated with the presence of eosinophils and
      neutrophils in UC and granulomas in CD patients. Our studies indicate that the
      overexpression of metalloproteinases and weaker expression of their inhibitors
      may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may
      be a potential therapeutic target and the use of their inhibitors may
      significantly reduce UC progression. 

PMID- 27034657
TI  - Gender Difference in Renal Blood Flow Response to Angiotensin II Administration
      after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor.
AB  - Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney
      failure, and it may interact with renin angiotensin system while angiotensin II
      (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the
      role of AT2R blockade on vascular response to Ang II after I/R in rats. Methods.
      Male and female rats were subjected to 30 min renal ischemia followed by
      reperfusion. Two groups of rats received either vehicle or AT2R antagonist,
      PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were
      assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at
      controlled renal perfusion pressure (RPP). Results. Vehicle or antagonist did not
      alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion,
      RBF decreased insignificantly in female treated with PD123319 (P = 0.07). Ang II
      reduced RBF and increased renal vascular resistance (RVR) in a dose-related
      fashion (P dose < 0.0001), and PD123319 intensified the reduction of RBF response
      in female (P group < 0.005), but not in male rats. Conclusion. The impact of the
      AT2R on vascular responses to Ang II in renal I/R injury appears to be sexually
      dimorphic. PD123319 infusion promotes these hemodynamic responses in female more
      than in male rats. 

PMID- 27034658
TI  - Anterior Urethral Stricture Disease Negatively Impacts the Quality of Life of
      Family Members.
AB  - Purpose. To quantify the quality of life (QoL) distress experienced by immediate
      family members of patients with urethral stricture via a questionnaire given
      prior to definitive urethroplasty. The emotional, social, and physical effects of
      urethral stricture disease on the QoL of family members have not been previously
      described. Materials and Methods. A questionnaire was administered prospectively
      to an immediate family member of 51 patients undergoing anterior urethroplasty by
      a single surgeon (SBB). The survey was comprised of twelve questions that
      addressed the emotional, social, and physical consequences experienced as a
      result of their loved one. Results. Of the 51 surveyed family members, most were
      female (92.2%), lived in the same household (86.3%), and slept in the same room
      as the patient (70.6%). Respondents experienced sleep disturbances (56.9%) and
      diminished social lives (43.1%). 82.4% felt stressed by the patient's surgical
      treatment, and 83.9% (26/31) felt that their intimacy was negatively impacted.
      Conclusions. Urethral stricture disease has a significant impact on the family
      members of those affected. These effects may last decades and include sleep
      disturbance, decreased social interactions, emotional stress, and impaired sexual
      intimacy. Treatment of urethral stricture disease should attempt to mitigate the
      impact of the disease on family members as well as the patient. 

PMID- 27034659
TI  - Assessment of Potential Live Kidney Donors and Computed Tomographic Renal
      Angiograms at Christchurch Hospital.
AB  - Aims. To examine the outcome of potential live kidney donors (PLKD) assessment
      program at Christchurch Hospital and, also, to review findings of Computed
      Tomographic (CT) renal angiograms that led to exclusion in the surgical
      assessment. Methods. Clinical data was obtained from the database of kidney
      transplants, Proton. Radiological investigations were reviewed using the hospital
      database, Eclair. The transplant coordinator was interviewed to clarify
      information about PLKD who did not proceed to surgery, and a consultant
      radiologist was interviewed to explain unfavorable findings on CT renal
      angiograms. Results. 162 PLKD were identified during the period January 04-June
      08. Of those, 65 (40%) proceeded to have nephrectomy, 15 were accepted and
      planned to proceed to surgery, 13 were awaiting further assessment, and 69
      (42.5%) did not proceed to nephrectomy. Of the 162 PLKD, 142 (88%) were directed
      donors. The proportion of altruistic PLKD who opted out was significantly higher
      than that of directed PLKD (45% versus 7%, P = 0.00004). Conclusions. This audit
      demonstrated a positive experience of live kidney donation at Christchurch
      Hospital. CT renal angiogram can potentially detect incidental or controversial
      pathologies in the kidney and the surrounding structures. Altruistic donation
      remains controversial with higher rates of opting out. 

PMID- 27034660
TI  - Prevalence, Risk Factors, and Clinical Relevance of Fluoroquinolone-Resistant
      Organisms in Rectal Cultures: Should We Target Antibiotic Prophylaxis Prior to
      Prostate Biopsy?
AB  - The rise of infectious complications after prostate biopsy has been linked to the
      growing resistance of enterobacteria to fluoroquinolone (FQ) antibiotics. In this
      review, we investigated the potential benefit of targeted antibiotic prophylaxis
      based on rectal cultures prior to prostate biopsy. An electronic search for all
      related literature published in English was performed from April until June 2015
      using the MEDLINE and EMBASE databases. Data were obtained regarding the true
      prevalence of FQ-resistant bacteria in the rectum of patients, the identification
      of those patients at risk of harbouring FQ-resistant bacteria, the risk of
      infectious complications after transrectal prostate biopsy in patients with FQ
      resistant bacteria, and the effect of targeted prophylaxis. Although there is
      limited evidence that a targeted approach might be beneficial, we conclude that
      current studies on the use of rectal cultures in the prebiopsy setting have too
      many limitations and confounding variables to definitely accept this approach in
      clinical practice. Whether this methodology is useful in a certain region will
      greatly depend on local fluoroquinolone-resistance rates. 

PMID- 27034661
TI  - Towards mHealth Systems for Support of Psychotherapeutic Practice: A Qualitative
      Study of Researcher-Clinician Collaboration in System Design and Evaluation.
AB  - We examined clinicians' and researchers' experiences from participation in
      collaborative research on the introduction of Internet and mobile information
      systems (mHealth systems) in psychotherapeutic routines. The study used grounded
      theory methodology and was set in a collaboration that aimed to develop and
      evaluate mHealth support of psychotherapy provided to young people. Soundness of
      the central objects developed in the design phase (the collaboration contract,
      the trial protocol, and the system technology) was a necessary foundation for
      successful collaborative mHealth research; neglect of unanticipated
      organizational influences during the trial phase was a factor in collaboration
      failure. The experiences gained in this study can be used in settings where
      collaborative research on mHealth systems in mental health is planned. 

PMID- 27034662
TI  - Comparative Evaluation of Pain Scores during Periodontal Probing with or without
      Anesthetic Gels.
AB  - Context. The initial periodontal examination which includes full-mouth
      periodontal probing is one of the discomforting procedures for a patient. Aim. To
      evaluate the efficacy of two local anesthetic gels in the reduction of pain
      during periodontal probing using Florida probe in CGP patients in comparison with
      manual probing. Materials and Methods. Ninety systemically healthy patients with
      moderate to severe CGP patients were recruited. In each patient, the quadrants
      were randomly assigned to manual probing with UNC-15 probe, probing with Florida
      probe, and Florida probing with lidocaine 10% gel and with benzocaine 20% gel. In
      the quadrants undergoing probing with anesthetic gels, the sites were isolated
      and the gel was injected using syringe and a blunt-end cannula. Pain was measured
      using 10 mm horizontal VAS. Statistical Analysis. The analysis was carried out
      using SPSS version 18. The comparison of mean VAS scores was done using repeated
      measures ANOVA with post hoc Bonferroni test. Results. Mean VAS for manual
      probing was significantly more than Florida probing. Further, the mean VAS score
      for Florida probing was higher than the two gels. Conclusion. It is suggested
      that the gels might be useful in reducing pain experienced during full-mouth
      periodontal probing in patients with CGP. 

PMID- 27034663
TI  - In Silico Approach for SAR Analysis of the Predicted Model of DEPDC1B: A Novel
      Target for Oral Cancer.
AB  - With the incidence rate of oral carcinogenesis increasing in the Southeast-Asian
      countries, due to increase in the consumption of tobacco and betel quid as well
      as infection from human papillomavirus, specifically type 16, it becomes crucial
      to predict the transition of premalignant lesion to cancerous tissue at an
      initial stage in order to control the process of oncogenesis. DEPDC1B,
      downregulated in the presence of E2 protein, was recently found to be
      overexpressed in oral cancer, which can possibly be explained by the disruption
      of the E2 open reading frame upon the integration of viral genome into the host
      genome. DEPDC1B mediates its effect by directly interacting with Rac1 protein,
      which is known to regulate important cell signaling pathways. Therefore, DEPDC1B
      can be a potential biomarker as well as a therapeutic target for diagnosing and
      curing the disease. However, the lack of 3D model of the structure makes the
      utilization of DEPDC1B as a therapeutic target difficult. The present study
      focuses on the prediction of a suitable 3D model of the protein as well as the
      analysis of protein-protein interaction between DEPDC1B and Rac1 protein using
      PatchDock web server along with the identification of allosteric or regulatory
      sites of DEPDC1B. 

PMID- 27034664
TI  - BacHbpred: Support Vector Machine Methods for the Prediction of Bacterial
      Hemoglobin-Like Proteins.
AB  - The recent upsurge in microbial genome data has revealed that hemoglobin-like
      (HbL) proteins may be widely distributed among bacteria and that some organisms
      may carry more than one HbL encoding gene. However, the discovery of HbL proteins
      has been limited to a small number of bacteria only. This study describes the
      prediction of HbL proteins and their domain classification using a machine
      learning approach. Support vector machine (SVM) models were developed for
      predicting HbL proteins based upon amino acid composition (AC), dipeptide
      composition (DC), hybrid method (AC + DC), and position specific scoring matrix
      (PSSM). In addition, we introduce for the first time a new prediction method
      based on max to min amino acid residue (MM) profiles. The average accuracy,
      standard deviation (SD), false positive rate (FPR), confusion matrix, and
      receiver operating characteristic (ROC) were analyzed. We also compared the
      performance of our proposed models in homology detection databases. The
      performance of the different approaches was estimated using fivefold cross
      validation techniques. Prediction accuracy was further investigated through
      confusion matrix and ROC curve analysis. All experimental results indicate that
      the proposed BacHbpred can be a perspective predictor for determination of HbL
      related proteins. BacHbpred, a web tool, has been developed for HbL prediction. 

PMID- 27034665
TI  - Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6
      Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period
      in Rats.
AB  - Exposure to persistent genotoxicants like benzo[a]pyrene (B[a]P) during postnatal
      days causes neurobehavioral changes in animal models. However, neurotoxic
      potential of B[a]P and its association with 6-hydroxydopamine (6-OHDA) induced
      neurobehavioral changes are yet to be explored. The growth of rat brain peaks at
      the first week of birth and continues up to one month with the attainment of
      adolescence. Hence, the present study was conducted on male Wistar rats at
      postnatal day 5 (PND 5) following single intracisternal administration of B[a]P
      to compare with neurobehavioral and neurotransmitter changes induced by 6-OHDA at
      PND 30. Spontaneous motor activity was significantly increased by 6-OHDA showing
      similar trend following B[a]P administration. Total distance travelled in novel
      open field arena and elevated plus maze was significantly increased following
      B[a]P and 6-OHDA administration. Neurotransmitter estimation showed significant
      alleviation of dopamine in striatum following B[a]P and 6-OHDA administration.
      Histopathological studies of striatum by hematoxylin and eosin (H&E) staining
      revealed the neurodegenerative potential of B[a]P and 6-OHDA. Our results
      indicate that B[a]P-induced spontaneous motor hyperactivity in rats showed
      symptomatic similarities with 6-OHDA. In conclusion, early postnatal exposure to
      B[a]P in rats causing neurobehavioral changes may lead to serious
      neurodegenerative consequences during adolescence. 

PMID- 27034667
TI  - Enchondroma versus Chondrosarcoma in Long Bones of Appendicular Skeleton:
      Clinical and Radiological Criteria-A Follow-Up.
AB  - As of today two types of cartilage tumors remain a challenge even for the
      orthopedic oncologist: enchondroma (E), a benign tumor, and chondrosarcoma (LGC),
      a malignant and low aggressiveness tumor. A prospective study of 133 patients
      with a cartilaginous tumor of low aggressiveness in the long bones of the
      appendicular skeleton was done to prove this difficult differential diagnosis.
      Parameters including medical history and radiological and nuclear imaging were
      collected and compared to the result of the biopsy. A scale of aggressiveness was
      applied to each patient according to the number of aggressiveness episodes
      present. A comparison of the results of the biopsy with the initial diagnosis
      made by the orthopedic oncologist based solely on clinical data and imaging tests
      was also made. Finally, a management algorithm for these cases was proposed. A
      statistical significance for LGC resulted from the parameter as follows: pain on
      palpation, involvement of cortical in either the CT or MRI, and Tc99 bone scan
      uptake equal or superior to anterosuperior iliac crest. In our series, a tumor
      scoring 5 points or higher in the scale of aggressiveness can have 50% more
      chance of being LGC. When compared with the gold standard (the biopsy), surgeon's
      initial judgement showed a sensitivity of 73.5% and a specificity of 94.1%. 

PMID- 27034666
TI  - The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective
      Study.
AB  - Objective. This prospective open trial aimed to evaluate the efficacy and safety
      of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD).
      Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism
      after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The
      drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if
      needed and tolerated. Clinical, biochemical, and hormonal parameters were
      evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects,
      4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of
      the study. UFC reductions of up to 52.1% were found in the rest. Only patients
      with UFC levels below 2.5-fold of the upper limit of normal achieved sustained
      UFC normalization. Improvements of clinical and biochemical parameters were also
      noted mostly in responsive patients. Typical isotretinoin side-effects were
      experienced by 7 patients (43.7%), though they were mild and mostly transient. We
      also observed that the combination of isotretinoin with cabergoline, in
      relatively low doses, may occasionally be more effective than either drug alone.
      Conclusions. Isotretinoin may be an effective and safe therapy for some CD
      patients, particularly those with mild hypercortisolism. 

PMID- 27034668
TI  - Prostate Cancer Screening in Jamaica: Results of the Largest National Screening
      Clinic.
AB  - Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer
      related deaths. Our aim was to evaluate the patterns of screening in the largest
      organized screening clinic in Jamaica at the Jamaica Cancer Society. A
      retrospective analysis of all men presenting for screening at the Jamaica Cancer
      Society from 1995 to 2005 was done. All patients had digital rectal examinations
      (DRE) and prostate specific antigen (PSA) tests done. Results of prostate
      biopsies were noted. 1117 men of mean age 59.9 +/- 8.2 years presented for
      screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most
      patients presented for only 1 screen. There was a gradual reduction in the mean
      age of presentation for screening over the period. Prostate biopsies were
      requested on 11% of screening visits; however, only 59% of these were done. 5.6%
      of all persons screened were found to have cancer. Of the cancers diagnosed,
      Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL
      (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica.
      However, compliance with regular maintenance visits and requests for confirmatory
      biopsies are poor. Screening needs intervention in the Jamaican population. 

PMID- 27034670
TI  - Serological Survey of Hantavirus in Inhabitants from Tropical and Subtropical
      Areas of Brazil.
AB  - Brazil has reported more than 1,600 cases of hantavirus cardiopulmonary syndrome
      (HPS) since 1993, with a 39% rate of reported fatalities. Using a recombinant
      nucleocapsid protein of Araraquara virus, we performed ELISA to detect IgG
      antibodies against hantavirus in human sera. The aim of this study was to analyze
      hantavirus antibody levels in inhabitants from a tropical area (Amazon region) in
      Rondonia state and a subtropical (Atlantic Rain Forest) region in Sao Paulo
      state, Brazil. A total of 1,310 serum samples were obtained between 2003 and 2008
      and tested by IgG-ELISA, and 82 samples (6.2%), of which 62 were from the
      tropical area (5.8%) and 20 from the subtropical area (8.3%), tested positive.
      Higher levels of hantavirus antibody were observed in inhabitants of the populous
      subtropical areas compared with those from the tropical areas in Brazil. 

PMID- 27034669
TI  - The Influences of Health Insurance and Access to Information on Prostate Cancer
      Screening among Men in Dominican Republic.
AB  - Objectives. Although research demonstrates the public health burden of prostate
      cancer among men in the Caribbean, relatively little is known about the factors
      that underlie the low levels of testing for the disease among this population.
      Study Design. A cross-sectional study of prostate cancer testing behaviours among
      men aged 40-60 years in Dominican Republic using the Demographic and Health
      Survey (2013). Methods. We use hierarchical binary logit regression models and
      average treatment effects combined with propensity score matching to explore the
      determinants of prostate screening as well as the average effect of health
      insurance coverage on screening. The use of hierarchical binary logit regression
      enabled us to control for the effect of unobserved heterogeneity at the cluster
      level that may affect prostate cancer testing behaviours. Results. Screening
      varied significantly with health insurance coverage, knowledge of cholesterol
      level, education, and wealth. Insured men were more likely to test for prostate
      cancer (OR = 1.65, p = 0.01) compared to the uninsured. Conclusions. The
      expansion and restructuring of Dominican Republic universal health insurance
      scheme to ensure equity in access may improve health access that would
      potentially impact positively on prostate cancer screening among men. 

PMID- 27034671
TI  - Oral Gingival Cell Cigarette Smoke Exposure Induces Muscle Cell Metabolic
      Disruption.
AB  - Cigarette smoke exposure compromises health through damaging multiple
      physiological systems, including disrupting metabolic function. The purpose of
      this study was to determine the role of oral gingiva in mediating the deleterious
      metabolic effects of cigarette smoke exposure on skeletal muscle metabolic
      function. Using an in vitro conditioned medium cell model, skeletal muscle cells
      were incubated with medium from gingival cells treated with normal medium or
      medium containing suspended cigarette smoke extract (CSE). Following incubation
      of muscle cells with gingival cell conditioned medium, muscle cell mitochondrial
      respiration and insulin signaling and action were determined as an indication of
      overall muscle metabolic health. Skeletal muscle cells incubated with conditioned
      medium of CSE-treated gingival cells had a profound reduction in mitochondrial
      respiration and respiratory control. Furthermore, skeletal muscle cells had a
      greatly reduced response in insulin-stimulated Akt phosphorylation and glycogen
      synthesis. Altogether, these results provide a novel perspective on the mechanism
      whereby cigarette smoke affects systemic metabolic function. In conclusion, we
      found that oral gingival cells treated with CSE create an altered milieu that is
      sufficient to both disrupted skeletal muscle cell mitochondrial function and
      insulin sensitivity. 

PMID- 27034672
TI  - Association between Self-Reported Bruxism and Sleeping Patterns among Dental
      Students in Saudi Arabia: A Cross-Sectional Study.
AB  - Objectives. The aim of this cross-sectional study was to identify sleeping
      patterns among dental students and their association with self-reported bruxism
      in Riyadh Colleges of Dentistry and Pharmacy (RCsDP). Methods. A cross-sectional
      study was performed including 549 students (67 men and 482 women). A structured
      questionnaire was adopted from The PSQI (The Pittsburgh Sleep Questionnaire
      Index) used for data collection. It included questions which are categorized into
      sleeping habits, sleep-related symptoms, and additional questions concerning
      bruxism. This questionnaire was randomly distributed among all college
      preclinical and postclinical students. Sleep bruxism diagnosis was based on self
      reported data. The data were analyzed using Chi-square tests through SPSS
      software for Windows. Results. Statistical analyses revealed significant
      correlations between self-reported bruxism and sleeping habits including sleep
      initiation (chi (2) = 22.6, p = 0.000), continuous sleep until morning (chi (2) =
      19.2, p = 0.001), nighttime sleep duration (chi (2) = 20.2, p = 0.000), and
      length of daytime naps (chi (2) = 28.35, p = 0.000). There was an association
      between self-reported bruxism and sleeping-related symptoms including awakening
      early in the morning before the usual time without a cause (chi (2) = 16.52, p =
      0.000) and increased nightmares (chi (2) = 13.7, p = 0.001). Conclusions. Poor
      sleeping pattern was an important factor among dental students, who reported
      sleep bruxism. 

PMID- 27034674
TI  - Nitric Oxide Concentration and Other Salivary Changes after Insertion of New
      Complete Dentures in Edentulous Subjects.
AB  - Objective. To assess changes in levels of salivary nitric oxide (NO) after
      insertion of new complete dentures and its association with clinical and salivary
      parameters. Methods. Nineteen fully edentulous subjects were included, mean age
      64.4. Unstimulated whole saliva was collected before and after insertion of the
      dentures, at follow-up visits, and after 12 months. The concentration of the
      final stable NO product (nitrite) was measured by a colorimetric assay based on
      the Griess reaction. Clinical parameters were assessed during all clinical
      visits. Results. Functional adaptation to the dentures progressively improved,
      with no complaints at the long-term follow-up. NO concentration was not
      influenced by the level of functional adaptation, presence of injuries to the
      mucosa, salivary flow, and saliva viscosity. Pairwise comparison showed a
      reduction in NO concentration at the first follow-up compared to baseline values
      but differences were not statistically significant. Significant differences were
      observed in NO concentrations at the long-term follow-up when compared to the
      first (p = 0.024) and second (p = 0.027) visits. Conclusion. NO concentration
      reduced after denture insertion and returned to baseline levels in the long-term
      follow-up. This appears to be an autonomic response of the body and provides
      valuable complementary information for the management of the edentulous patient. 

PMID- 27034673
TI  - Experimentally Induced Pulpal Lesion and Substance P Expression: Effect of
      Ketoprofen-A Preliminary Study.
AB  - Objectives. To evaluate substance P (SP) and the effect of ketoprofen
      administration, a nonsteroidal anti-inflammatory drug (NSAID), on SP in the pulp
      of upper third molars with experimentally induced pulpal lesion. Materials and
      Methods. A sample of 20 young systemically healthy adults of both sexes,
      nonsmokers, with a healthy upper third molar to extract for orthodontic purposes,
      was selected. Prior to the procedure, an inflammatory process was generated by
      mechanical exposure of the pulp. After 15 minutes, the pulp was collected using a
      sterile barbed broach. SP levels were determined by using a commercially
      available enzyme immunoassay (ELISA) kit. The subjects were randomly divided into
      two groups: group 1 received a dose of ketoprofen 30 minutes prior to the
      experimental procedure. The subjects of group 2 did not receive any kind of drug
      administration. The patients were asked to complete a diary on the postoperative
      pain. Results. No statistically significant difference could be detected in SP
      expression between the two groups. In group 1, pain manifestation was
      significantly delayed in comparison with group 2. Conclusions. Preventive
      administration of ketoprofen did not significantly affect the pulpal levels of SP
      but resulted in a significantly postponed manifestation of pain after extraction.

PMID- 27034675
TI  - High Performance Liquid Chromatographic Assay for the Simultaneous Determination
      of Posaconazole and Vincristine in Rat Plasma.
AB  - Purpose. Developing a validated HPLC-DAD method for simultaneous determination of
      posaconazole (PSZ) and vincristine (VCR) in rat plasma. Methods. PSZ, VCR, and
      itraconazole (ITZ) were extracted from 200 MUL plasma using diethyl ether in the
      presence of 0.1 M sodium hydroxide solution. The organic layer was evaporated in
      vacuo and dried residue was reconstituted and injected through HC-C18 (4.6 * 250
      mm, 5 MUm) column. In the mobile phase, acetonitrile and 0.015 M potassium
      dihydrogen orthophosphate (30 : 70 to 80 : 20, linear gradient over 7 minutes)
      pumped at 1.5 mL/min. VCR and PSZ were measured at 220 and 262 nm, respectively.
      Two Sprague Dawley rats were orally dosed PSZ followed by iv dosing of VCR and
      serial blood sampling was performed. Results. VCR, PSZ, and ITZ were successfully
      separated within 11 min. Calibration curves were linear over the range of 50-5000
      ng/mL for both drugs. The CV% and % error of the mean were <=18% and limit of
      quantitation was 50 ng/mL for both drugs. Rat plasma concentrations of PSZ and
      VCR were simultaneously measured up to 72 h and their calculated pharmacokinetics
      parameters were comparable to the literature. Conclusion. The assay was validated
      as per ICH guidelines and is appropriate for pharmacokinetics drug-drug
      interaction studies. 

PMID- 27034676
TI  - Review on Haploidentical Hematopoietic Cell Transplantation in Patients with
      Hematologic Malignancies.
AB  - Allogenic hematopoietic cell transplantation (HSCT) is typically the preferred
      curative therapy for adult patients with acute myeloid leukemia, but its use has
      been reduced as a consequence of limited donor availability in the form of either
      matched-related donors (MRD) or matched-unrelated donors (MUD). Alternative
      options such as unrelated umbilical cord blood (UCB) transplantation and
      haploidentical HSCT have been increasingly studied in the past few decades to
      overcome these obstacles. A human leukocyte antigen- (HLA-) haploidentical donor
      is a recipient's relative who shares an exact haplotype with the recipient but is
      mismatched for HLA genes on the unshared haplotype. These dissimilarities pose
      several challenges to the outcomes of the patient receiving such a type of HSCT,
      including higher rates of bidirectional alloreactivity and graft failure. In the
      past 5 years, however, several nonrandomized studies have shown promising results
      in terms of graft success and decreased rates of alloreactivity, in part due to
      newer grafting techniques and graft-versus-host disease (GVHD) prophylaxis. We
      present here a summary and review of the latest results of these studies as well
      as a brief discussion on the advantages and challenges of haploidentical HSCT. 

PMID- 27034677
TI  - Nasopharyngeal Tuberculosis: Epidemiology, Mechanism of Infection, Clinical
      Manifestations, and Management.
AB  - Nasopharyngeal tuberculosis (NPTB) is a noteworthy disease especially in its
      worldwide spread of the Mycobacterium infection. Although NPTB has been
      identified in less than one percent of TB cases, recent multiple case reports
      indicate an either increased awareness or incidence of this disease. The most
      helpful diagnostic tool is an uncomplicated nasopharyngeal biopsy. However, NPTB
      is usually ignored because it has varied clinical manifestations and similar
      presentations with other more common head and neck diseases. Furthermore, the
      most common presenting symptom is cervical lymphadenopathy mimicking
      nasopharyngeal carcinoma, a more common and serious disease. Treatment outcomes
      of NPTB are good in both HIV-positive or HIV-negative patients. In addition,
      pulmonary tuberculosis association was reported in wide range between 8.3% and
      82% which should be considered in a treatment program. In conclusion, early
      diagnosis and management in NPTB can be achieved by (1) increased awareness of
      this disease, (2) improvement in knowledge regarding clinical manifestations, and
      (3) improvement of diagnostic techniques. 

PMID- 27034678
TI  - Association between Maternal Pelvis Height and Intrapartum Foetal Head Moulding
      in Ugandan Mothers with Spontaneous Vertex Deliveries.
AB  - Introduction. In Sub-Saharan Africa, excessive foetal head moulding is commonly
      associated with cephalopelvic disproportion and obstructed labour. This study set
      out to determine the associations of maternal pelvis height and maternal height
      with intrapartum foetal head moulding. Methods. This was a multisite secondary
      analysis of maternal birth records of mothers with singleton pregnancies ending
      in a spontaneous vertex delivery. A summary of the details of the pregnancy and
      delivery records were reviewed and analysed using multilevel logistic regression
      respect to foetal head moulding. The alpha level was set at P < 0.05. Results.
      412 records were obtained, of which 108/385 (28%) observed foetal head moulding.
      There was a significant reduction in risk of foetal head moulding with increasing
      maternal height (Adj. IRR 0.97, P = 0.05), maternal pelvis height (Adj. IRR 0.88,
      P < 0.01), and raptured membranes (Adj. IRR 0.10, P < 0.01). There was a
      significant increased risk of foetal head moulding with increasing birth weight
      (Adj. IRR 1.90, P < 0.01) and duration of monitored active labour (Adj. IRR 1.21,
      P < 0.01) in the final model. Conclusion. This study showed that increasing
      maternal height and maternal pelvis height were associated with a significant
      reduction in intrapartum foetal head moulding. 

PMID- 27034679
TI  - Paroxysmal Amnesia Attacks due to Hashimoto's Encephalopathy.
AB  - Hashimoto's encephalopathy is a rare disease which is thought to be autoimmune
      and steroid responsive. The syndrome is characterized by cognitive impairment,
      encephalopathy, psychiatric symptoms, and seizures associated with increased
      level of anti-thyroid antibodies. The exact pathophysiology underlying cerebral
      involvement is still lesser known. Although symptoms suggest a nonlesional
      encephalopathy in most of the cases, sometimes the clinical appearance can be
      subtle and may not respond to immunosuppressants or immunomodulatory agents. Here
      we report a case who presented with drowsiness and amnestic complaints associated
      with paroxysmal electroencephalography (EEG) abnormalities which could be treated
      only with an antiepileptic drug. 

PMID- 27034680
TI  - Combining Body Mass and Shape Indices in Clinical Practice.
AB  - We present preliminary clinical experience with combined consideration of the
      commonly used BMI (body mass index) and the newly developed ABSI (a body shape
      index) using a point of care anthropometric calculator for comparisons of index
      values and associated relative risks to population normals. In a series of 282
      patients, BMI and ABSI were close to being independently distributed, supporting
      the value of considering both indices. Three selected cases illustrate scenarios
      where assessment of ABSI together with BMI could inform patient care and
      counseling. These data suggest that combined assessment of BMI and ABSI may prove
      useful in clinical practice. 

PMID- 27034681
TI  - Fulminant Pseudomembranous Colitis Presenting as Sigmoid Stricture and Severe
      Polyposis with Clinical Response to Intracolonic Vancomycin.
AB  - Clostridium difficile infection (CDI) is the most common cause of antibiotic
      associated diarrhea. Severe diseases carry significant morbidities such as septic
      shock, acute kidney injury, bowel perforation, and mortality. Immunocompromising
      conditions increase the risk of developing the disease but whether these
      individuals suffer a more fulminant course or warrant a more potent first-line
      treatment is still controversial issue. Hereby we report a case of a cirrhotic
      patient with life-threatening pseudomembranous colitis complicated by colonic
      stricture, initially refractory to standard treatment but with subsequent
      improvement on intracolonic vancomycin. 

PMID- 27034682
TI  - B-Cell Chronic Lymphocytic Leukemia with 11q22.3 Rearrangement in Patient with
      Chronic Myeloid Leukemia Treated with Imatinib.
AB  - The coexistence of two diseases chronic myeloid leukemia (CML) and B-cell chronic
      lymphocytic leukemia (B-CLL) is a rare phenomenon. Both neoplastic disorders have
      several common epidemiological denominators (they occur more often in men over 50
      years of age) but different origin and long term prognosis. In this paper we
      described the clinical and pathological findings in patient with CML in major
      molecular response who developed B-CLL with 11q22.3 rearrangement and Coombs
      positive hemolytic anemia during the imatinib treatment. Due to the presence of
      the symptoms of autoimmune hemolytic anemia and optimal CML response to the
      imatinib treatment, the decision about combined therapy with prednisone and
      imatinib was made. During the follow-up, the normalization of complete blood
      count and resolution of peripheral lymphadenopathy were noted. The hematologic
      response of B-CLL was diagnosed. The repeated FISH analysis of cultured
      peripheral blood lymphocytes showed 2% of cells carrying 11q22.3 rearrangement.
      At the same time, molecular monitoring confirmed the deep molecular response of
      CML. The effectiveness of such combination in the described case raises the
      question about the best therapeutic option in such situation, especially in
      patients with good imatinib tolerance and optimal response. 

PMID- 27034683
TI  - Evaluation of Tissue Homogenization to Support the Generation of GMP-Compliant
      Mesenchymal Stromal Cells from the Umbilical Cord.
AB  - Recent studies have demonstrated that the umbilical cord (UC) is an excellent
      source of mesenchymal stromal cells (MSCs). However, current protocols for
      extracting and culturing UC-MSCs do not meet current good manufacturing practice
      (cGMP) standards, in part due to the use of xenogeneic reagents. To support the
      development of a cGMP-compliant method, we have examined an enzyme-free isolation
      method utilizing tissue homogenization (t-H) followed by culture in human
      platelet lysate (PL) supplemented media. The yield and viability of cells after t
      H were comparable to those obtained after collagenase digestion (Col-D).
      Importantly, kinetic analysis of cultured cells showed logarithmic growth over 10
      tested passages, although the rate of cell division was lower for t-H as compared
      to Col-D. This slower growth of t-H-derived cells was also reflected in their
      longer population doubling time. Interestingly, there was no difference in the
      expression of mesenchymal markers and trilineage differentiation potential of
      cells generated using either method. Finally, t-H-derived cells had greater
      clonogenic potential compared to Col-D/FBS but not Col-D/PL and were able to
      maintain CFU-F capacity through P7. This bench scale study demonstrates the
      possibility of generating therapeutic doses of good quality UC-MSCs within a
      reasonable length of time using t-H and PL. 

PMID- 27034684
TI  - Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia.
AB  - Emerging evidence suggests that the muscle microenvironment plays a prominent
      role in cancer cachexia. We recently showed that NF-kB-induced Pax7
      overexpression impairs the myogenic potential of muscle precursors in cachectic
      mice, suggesting that lowering Pax7 expression may be beneficial in cancer
      cachexia. We evaluated the muscle regenerative potential after acute injury in
      C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses
      confirmed that the delayed muscle regeneration observed in muscles form tumor
      bearing mice was associated with a persistent local inflammation and Pax7
      overexpression. Physical activity is known to exert positive effects on cachectic
      muscles. However, the mechanism by which a moderate voluntary exercise
      ameliorates muscle wasting is not fully elucidated. To verify if physical
      activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel
      equipped cages and we found that voluntary wheel running downregulated Pax7
      expression in muscles from tumor-bearing mice. As expected, downregulation of
      Pax7 expression was associated with a rescue of muscle mass and fiber size. Our
      findings shed light on the molecular basis of the beneficial effect exerted by a
      moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore,
      we propose voluntary exercise as a physiological tool to counteract the
      overexpression of Pax7 observed in cancer cachexia. 

PMID- 27034685
TI  - Heavy Metal Contamination of Soils around a Hospital Waste Incinerator Bottom Ash
      Dumps Site.
AB  - Waste incineration is the main waste management strategy used in treating
      hospital waste in many developing countries. However, the release of dioxins,
      POPs, and heavy metals in fly and bottom ash poses environmental and public
      health concerns. To determine heavy metal (Hg, Pb, Cd, Cr, and Ag) in levels in
      incinerator bottom ash and soils 100 m around the incinerator bottom ash dump
      site, ash samples and surrounding soil samples were collected at 20 m, 40 m, 60
      m, 80 m, 100 m, and 1,200 m from incinerator. These were analyzed using the
      absorption spectrophotometer method. The geoaccumulation (I geo) and pollution
      load indices (PLI) were used to assess the level of heavy metal contamination of
      surrounding soils. The study revealed high concentrations in mg/kg for, Zn
      (16417.69), Pb (143.80), Cr (99.30), and Cd (7.54) in bottom ash and these were
      above allowable limits for disposal in landfill. The study also found soils
      within 60 m radius of the incinerator to be polluted with the metals. It is
      recommended that health care waste managers be educated on the implication of
      improper management of incinerator bottom ash and regulators monitor hospital
      waste incinerator sites.

PMID- 27034686
TI  - Anti-Inflammatory Activity of Triterpenes Isolated from Protium paniculatum Oil
      Resins.
AB  - Protium is the main genus of the Burseraceae family and one of the most common
      genera in South America, with an important species called "breu." Gum and oil
      resins of this species are used as tonic and stimulant and for the treatment of
      ulcers and inflammation. The present study aims to isolate and investigate the
      anti-inflammatory activity of triterpene compounds isolated from oil-resin of
      Protium paniculatum. The pentacyclic triterpenes alpha,beta-amyrin, acetylated
      alpha,beta-amyrin, alpha,beta-amyrone, and brein/maniladiol did not alter the
      viability of murine J774 macrophages (IC50 > 20 ug/mL), with the exception of
      mixture of brein/maniladiol which showed moderate cytotoxic activity. Also it was
      observed that compounds at 10 ug/mL inhibited more than 80% of production of
      NO(*), although only alpha,beta-amyrin was able to inhibit the production of TNF
      alpha (52.03 +/- 2.4%). The compounds inhibited the production of IL-6 and
      induced the production of IL-10 in murine J774 macrophages stimulated by LPS.
      alpha,beta-Amyrone inhibited the expression of COX-2 and also inhibited the
      formation of paw or ear edema in rats and mice, having a quick and immediate
      effect. This study may provide the basis for future investigations on the
      therapeutic role of alpha,beta-amyrone in treating inflammation. 

PMID- 27034687
TI  - Ultrastructure of a Mobile Threadlike Tissue Floating in a Lymph Vessel.
AB  - Observations of the primo vascular system (PVS) floating in lymph ducts were
      reported by various groups. There have been, however, no studies on the
      ultrastructure of the entire cross section of a primo vessel (PV) inside a lymph
      vessel with a transmission electron microscope (TEM). In the current study we
      took the TEM images of a cross section of the PV inside a lymph vessel. We used
      the Alcian blue staining method for the finding of the target PV in a lymphatic
      vessel by injecting the dye into the inguinal lymph nodes. The stained PV was
      harvested together with the lymph vessel and some parts of the specimens were
      used for studying with optical microscopes. Some other parts were treated
      according to a standard protocol for TEM. As the results the TEM study revealed
      the loosely distributed collagen fibers with plenty of empty spaces and the
      lumens with the endothelial nuclei. It turned out to be very similar to the
      ultrastructure of the PVs observed on the surfaces of internal organs. It also
      showed how compactly the PV is surrounded with lymphocytes. In conclusion, the
      detailed morphological features like the distribution of fibers in the PV were
      revealed and shown to be similar to another kind of the PV on the surfaces of
      internal organs. 

PMID- 27034688
TI  - Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer's
      Disease Rat Models.
AB  - Stem cell-based therapy is a promising treatment strategy for neurodegenerative
      diseases such as Alzheimer's disease (AD). However, the mechanism underlying the
      maintenance of renewal and replacement capabilities of endogenous progenitor
      cells or engrafted stem cells in a pathological environment remains elusive. To
      investigate the effect of astragaloside IV (ASI) on the proliferation and
      differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from
      the hippocampus of E14 rat embryos, treated the cells with ASI, and then
      transplanted the cells into the hippocampus of rat AD models. In vitro
      experimentation showed that 10(-5) M ASI induced NSCs to differentiate into beta
      tubulin III(+) and GFAP(+) cells. NSCs transplantation into rat AD models
      resulted in improvements in learning and memory, especially in the ASI-treated
      groups. ASI treatment resulted in an increase in the number of beta-tubulin
      III(+) cells in the hippocampus. Further investigation showed that ASI inhibited
      PS1 expression in vitro and in vivo. The high-dose ASI downregulated the Notch
      intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In
      conclusion, ASI treatment resulted in improvements in learning and memory of AD
      models by promoting NSC proliferation and differentiation partly through the
      Notch signal pathway. 

PMID- 27034689
TI  - Recovery of Olfactory Function in Postviral Olfactory Dysfunction Patients after
      Acupuncture Treatment.
AB  - Introduction. The aims of this study were to assess the impact of traditional
      Chinese acupuncture (TCA) in postviral olfactory dysfunction (PVOD) patients who
      were refractory to standardized treatment and to compare the results with the
      impact observed in an observation group. Methods. Fifty patients who presented to
      the outpatient clinic with PVOD and were refractory to standardized treatment
      were included: 25 were treated with TCA and 25 patients were simply observed. A
      subjective olfactory test was performed using the University of Pennsylvania
      Smell Identification Test (UPSIT). The effects of TCA were compared with the
      results obtained in the observation group. Results. Improved olfactory function
      was observed in eleven patients treated with TCA compared with four patients in
      the observation group. This study revealed significantly improved olfactory
      function outcomes in patients who underwent acupuncture compared with the
      observation group. No significant differences in olfaction recovery were found
      according to age, gender, or duration of disease between the two groups; however,
      hyposmic patients recovered at a higher rate than anosmic patients. Conclusion.
      TCA may aid the treatment of PVOD patients who are refractory to drugs or other
      therapies. 

PMID- 27034690
TI  - Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes.
AB  - Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism
      of xenobiotics. In this study, the CYP450 isoforms involved in xanthotoxol
      metabolism were identified using recombinant CYP450s. In addition, the inhibitory
      effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic
      parameters were determined using human liver microsomes. CYP1A2, one of CYP450s,
      played a key role in the metabolism of xanthotoxol compared to other CYP450s.
      Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other
      isoenzymes with the IC50 of 7.43 MUM for CYP3A4 and 27.82 MUM for CYP1A2. The
      values of inhibition kinetic parameters (Ki) were 21.15 MUM and 2.22 MUM for
      CYP1A2 and CYP3A4, respectively. The metabolism of xanthotoxol obeyed the typical
      monophasic Michaelis-Menten kinetics and V max, K m , and CLint values were
      calculated as 0.55 nmol.min(-1).mg(-1), 8.46 MUM, and 0.06 mL.min(-1).mg(-1). In
      addition, the results of molecular docking showed that xanthotoxol was bound to
      CYP1A2 with hydrophobic and pi-pi bond and CYP3A4 with hydrogen and hydrophobic
      bond. We predicted the hepatic clearance (CL H ) and the CL H value was 15.91
      mL.min(-1).kg(-1) body weight. These data were significant for the application of
      xanthotoxol and xanthotoxol-containing herbs. 

PMID- 27034691
TI  - Gelam Honey Attenuates the Oxidative Stress-Induced Inflammatory Pathways in
      Pancreatic Hamster Cells.
AB  - Purpose. Type 2 diabetes consists of progressive hyperglycemia and insulin
      resistance, which could result from glucose toxicity, inflammatory cytokines, and
      oxidative stress. In the present study we investigated the effect of Gelam honey
      and quercetin on the oxidative stress-induced inflammatory pathways and the
      proinflammatory cytokines. Methods. HIT-T15 cells were cultured and preincubated
      with the extract of Gelam honey (20, 40, 60, and 80 MUg/mL), as well as quercetin
      (20, 40, 60, and 80 MUM), prior to stimulation by 20 and 50 mM glucose. Results.
      HIT-T15 cells cultured under hyperglycemic condition showed a significant
      increase in the inflammatory pathways by phosphorylating JNK, IKK-beta, and IRS-1
      at Ser307 (p < 0.05). There was a significant decrease in the phosphorylation of
      Akt at Ser473 (p < 0.05). Pretreatment with Gelam honey and quercetin reduced the
      expression of phosphorylated JNK, IKK-beta, and IRS-1, thereby significantly
      reducing the expression of proinflammatory cytokines like TNF-alpha, IL-6, and IL
      1beta (p < 0.05). At the same time there was a significant increase in the
      phosphorylated Akt showing the protective effects against inflammation and
      insulin resistance (p < 0.05). In conclusion, our data suggest the potential use
      of the extract from Gelam honey and quercetin in modulating the inflammation
      induced insulin signaling pathways. 

PMID- 27034692
TI  - In Vitro Anticancer Activity of a Nonpolar Fraction from Gynostemma pentaphyllum
      (Thunb.) Makino.
AB  - Gynostemma pentaphyllum (Thunb.) Makino (GpM) has been widely used in traditional
      Chinese medicine (TCM) for the treatment of various diseases including cancer.
      Most previous studies have focused primarily on polar fractions of GpM for
      anticancer activities. In this study, a nonpolar fraction EA1.3A from GpM showed
      potent growth inhibitory activities against four cancer cell lines with IC50
      ranging from 31.62 MUg/mL to 38.02 MUg/mL. Furthermore, EA1.3A also inhibited the
      growth of breast cancer cell MDA-MB-453 time-dependently, as well as its colony
      formation ability. EA1.3A induced apoptosis on MDA-MB-453 cells both dose
      dependently and time-dependently as analyzed by flow cytometry and verified by
      western blotting analysis of apoptosis marker cleaved nuclear poly(ADP-ribose)
      polymerase (cPARP). Additionally, EA1.3A induced cell cycle arrest in G0/G1
      phase. Chemical components analysis of EA1.3A by GC-MS revealed that this
      nonpolar fraction from GpM contains 10 compounds including four alkaloids, three
      organic esters, two terpenes, and one catechol substance, and all these compounds
      have not been reported in GpM. In summary, the nonpolar fraction EA1.3A from GpM
      inhibited cancer cell growth through induction of apoptosis and regulation of
      cell cycle progression. Our study shed light on new chemical bases for the
      anticancer activities of GpM and feasibilities to develop new anticancer agents
      from this widely used medicinal plant. 

PMID- 27034693
TI  - Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced
      Diabetic Rats.
AB  - Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb
      that is considered beneficial for health due to its antioxidant and antidiabetes
      properties, and so on. In this research, we try to determine the preventive
      effect of DO on the early complications of STZ-induced diabetic rats. Methods.
      Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ
      (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood
      glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and
      electroretinographic activity and hypoalgesia were investigated. Pathological
      sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results.
      Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and
      CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and
      reduced the hypoalgesia and histopathological changes of vital organs induced by
      hyperglycemia. The protective effect of DO in diabetic rats may be associated
      with its antioxidant activity, as evidenced by the marked increase in the serum
      level of glutathione peroxidase. However, DO had no significant effect on blood
      glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation
      is an effective treatment to prevent STZ-induced diabetic complications. 

PMID- 27034694
TI  - Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in
      Diseases Prevention and Treatment.
AB  - Neem (Azadirachta indica) is a member of the Meliaceae family and its role as
      health-promoting effect is attributed because it is rich source of antioxidant.
      It has been widely used in Chinese, Ayurvedic, and Unani medicines worldwide
      especially in Indian Subcontinent in the treatment and prevention of various
      diseases. Earlier finding confirmed that neem and its constituents play role in
      the scavenging of free radical generation and prevention of disease pathogenesis.
      The studies based on animal model established that neem and its chief
      constituents play pivotal role in anticancer management through the modulation of
      various molecular pathways including p53, pTEN, NF-kappaB, PI3K/Akt, Bcl-2, and
      VEGF. It is considered as safe medicinal plants and modulates the numerous
      biological processes without any adverse effect. In this review, I summarize the
      role of Azadirachta indica in the prevention and treatment of diseases via the
      regulation of various biological and physiological pathways. 

PMID- 27034695
TI  - Effect of Inhalation of Aromatherapy Oil on Patients with Perennial Allergic
      Rhinitis: A Randomized Controlled Trial.
AB  - This study aimed to investigate the effects of aromatherapy oil inhalation on
      symptoms, quality of life, sleep quality, and fatigue level among adults with
      perennial allergic rhinitis (PAR). Fifty-four men and women aged between 20 and
      60 were randomized to inhale aromatherapy oil containing essential oil from
      sandalwood, geranium, and Ravensara or almond oil (the placebo) for 5 minutes
      twice daily for 7 days. PAR symptoms determined by Total Nasal Symptom Score
      (TNSS), the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), sleep
      quality by Verran Synder-Halpern (VSH) scale, and fatigue level by Chalder
      Fatigue Scale (CFS) were assessed before and after intervention period. Compared
      with the placebo, the experimental group showed significant improvement in TNSS,
      especially in nasal obstruction. The aromatherapy group also showed significantly
      higher improvements in total score of RQLQ and CFS. These findings indicate that
      inhalation of certain aromatherapy oil helps relieve PAR symptoms, improve
      rhinitis-specific quality of life, and reduce fatigue in patients with PAR. In
      conclusion, inhalation of aromatherapy essential oil may have potential as an
      effective intervention to alleviate PAR. 

PMID- 27034696
TI  - ITPI: Initial Transcription Process-Based Identification Method of Bioactive
      Components in Traditional Chinese Medicine Formula.
AB  - Identification of bioactive components is an important area of research in
      traditional Chinese medicine (TCM) formula. The reported identification methods
      only consider the interaction between the components and the target proteins,
      which is not sufficient to explain the influence of TCM on the gene expression.
      Here, we propose the Initial Transcription Process-based Identification (ITPI)
      method for the discovery of bioactive components that influence transcription
      factors (TFs). In this method, genome-wide chip detection technology was used to
      identify differentially expressed genes (DEGs). The TFs of DEGs were derived from
      GeneCards. The components influencing the TFs were derived from STITCH. The
      bioactive components in the formula were identified by evaluating the molecular
      similarity between the components in formula and the components that influence
      the TF of DEGs. Using the formula of Tian-Zhu-San (TZS) as an example, the
      reliability and limitation of ITPI were examined and 16 bioactive components that
      influence TFs were identified. 

PMID- 27034697
TI  - Cytotoxic and Apoptotic Activities of Methanolic Subfractions of Scrophularia
      oxysepala against Human Breast Cancer Cell Line.
AB  - Herbs have played a positive role in medicine for thousands of years. In the
      current study, we investigated the cytotoxicity effects of Scrophularia oxysepala
      methanolic subfractions and the underlying mechanism responsible for cell death
      in human breast carcinoma (MCF-7 cells) and mouse fibrosarcoma (WEHI-164 cells).
      From 60% and 80% methanolic fractions, four subfractions (Fa, Fb, Fc, and Fd),
      yielded from size exclusion by Sephadex-LH20 column chromatography, were chosen.
      MTT assay revealed that all subfractions significantly reduced cell viability
      after 24 h and 36 h in a dose-dependent manner; it is worth noting that Fa and Fb
      subfractions had the highest cytotoxicity, with IC50 values of 52.9 and 61.2
      MUg/mL in MCF-7 at 24 h, respectively. ELISA, TUNEL, and DNA fragmentation assay
      revealed that antiproliferative effects of all subfractions were associated with
      apoptosis on cancer cells, without any significant effect on L929 normal cells.
      qRT-PCR data showed that, after 24 h treatment with IC50 concentrations of the
      subfractions, caspase-3 expression was increased in cancer cells while the
      expression of Bcl-2 was decreased. S. oxysepala methanolic subfractions induce
      apoptosis in MCF-7 and WEHI-164 cells and could be considered as a source of
      natural anticancer agents. 

PMID- 27034698
TI  - The Therapeutic Effects of the Chinese Herbal Medicine, Lang Chuang Fang Granule,
      on Lupus-Prone MRL/lpr Mice.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to
      severe multiorgan damage. Lang Chuang Fang (LCF) is a Chinese herbal medicine
      that is clinically prescribed for treating SLE. In this study, we examined the
      therapeutic effects of LCF granule on lupus-prone MRL/lpr mice. Female mice were
      randomly separated into six groups, and LCF treatment groups received LCF granule
      at the dosage of 0.97 g/kg/d, 1.95 g/kg/d, and 3.90 g/kg/d, respectively. Here,
      we found that, compared to the MRL/lpr mice, both the spleen coefficient and
      thymus coefficient were reduced in the LCF granule-treated mice. There was a
      marked downregulation in CRP and anti-dsDNA autoantibody and an evident
      upregulation of CH50 in LCF granule-treated mice. LCF granule treatment also
      obviously reduced the proteinuria, BUN, and SCr levels in MRL/lpr mice at the
      dosage of 0.97 g/kg/d, 1.95 g/kg/d, and 3.90 g/kg/d, indicating that LCF granule
      alleviated the renal injury of MRL/lpr mice. Furthermore, LCF granule decreased
      p65 NF-kappaB levels and increased Sirt1 and Nrf2 levels in the kidney tissues of
      MRL/lpr mice, which might elucidate the beneficial effects of LCF on lupus
      nephritis. In conclusion, this study demonstrates that LCF granule has
      therapeutic effects on lupus-prone MRL/lpr mice. 

PMID- 27034699
TI  - Effects of Whole-Body Electromyostimulation versus High-Intensity Resistance
      Exercise on Body Composition and Strength: A Randomized Controlled Study.
AB  - High-intensity (resistance) exercise (HIT) and whole-body electromyostimulation
      (WB-EMS) are both approaches to realize time-efficient favorable changes of body
      composition and strength. The purpose of this study was to determine the
      effectiveness of WB-EMS compared with the gold standard reference HIT, for
      improving body composition and muscle strength in middle-aged men. Forty-eight
      healthy untrained men, 30-50 years old, were randomly allocated to either HIT (2
      sessions/week) or a WB-EMS group (3 sessions/2 weeks) that exercised for 16
      weeks. HIT was applied as "single-set-to-failure protocol," while WB-EMS was
      conducted with intermittent stimulation (6 s WB-EMS, 4 s rest; 85 Hz, 350 ms)
      over 20 minutes. The main outcome parameters were lean body mass (LBM) as
      determined via dual-energy X-ray absorptiometry and maximum dynamic leg-extensor
      strength (isokinetic leg-press). LBM changes of both groups (HIT 1.25 +/- 1.44%
      versus WB-EMS 0.93 +/- 1.15%) were significant (p = .001); however, no
      significant group differences were detected (p = .395). Leg-extensor strength
      also increased in both groups (HIT 12.7 +/- 14.7%, p = .002, versus WB-EMS 7.3 +/
      10.3%, p = .012) with no significant (p = .215) between-group difference.
      Corresponding changes were also determined for body fat and back-extensor
      strength. Conclusion. In summary, WB-EMS can be considered as a time-efficient
      but pricy option to HIT-resistance exercise for people aiming at the improvement
      of general strength and body composition. 

PMID- 27034700
TI  - The Preventive Effect of Zuogui Wan on Offspring Rats' Impaired Glucose Tolerance
      Whose Mothers Had Gestational Diabetes Mellitus.
AB  - In this experiment, we used streptozotocin (STZ) to establish a model of
      gestational diabetes mellitus (GDM) rats, where Zuogui Wan was given to GDM rats.
      After pregnancy, offspring rats were divided into 4 groups: control group, high
      fat and sugar as the control group, GDM group, and Zuogui Wan GDM group. Rats in
      high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group were
      fed with high fat and sugar diet. Rats in control group were fed the basic diet.
      The means of 2hPG were higher than 7.8 mmol.L(-1) and lower than 11.1 mmol.L(-1)
      on the rats of GDM group on week 15, and IGT models were successful. Body weight,
      abdominal fat weight, the ratio of abdominal fat weight and body weight, fasting
      plasma glucose, 2hPG, insulin, leptin, total cholesterol, and low density
      lipoprotein (LDL) of Zuogui Wan GDM group were significantly lower than GDM
      group. The level of adiponectin in Zuogui Wan GDM group was significantly higher
      than GDM group. And we concluded that giving Zuogui Wan to GDM rats can have a
      preventive effect on the offsprings' IGT induced by high fat and sugar diet. 

PMID- 27034701
TI  - Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced
      Hepatorenal Toxicity in Rats.
AB  - Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has
      long been used in folk medicine, however, there is a lack of information
      concerning its protective effects against oxidative damage. The protective
      effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen
      induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats
      (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000
      mg/kg, respectively, orally for 30 days followed by acetaminophen administration.
      Silymarin (100 mg/kg) was administered as a standard drug over a similar
      treatment period. Our findings indicated that oral administration of
      acetaminophen induced severe hepatic and renal injuries associated with oxidative
      stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to
      control. Pretreatment with EECM prior to acetaminophen administration
      significantly improved all investigated biochemical parameters, that is,
      transaminase activities, alkaline phosphatase, lactate dehydrogenase, gamma
      glutamyl transferase activities and total bilirubin, total cholesterol,
      triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride
      ions, and TBARS levels. These findings were confirmed by histopathological
      examinations. The improvement was prominent in the group that received 1000 mg/kg
      EECM. These findings suggested that C. macroptera fruit could protect against
      acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of
      lipid peroxidation. 

PMID- 27034702
TI  - HCV monoinfection and HIV/HCV coinfection enhance T-cell immune senescence in
      injecting drug users early during infection.
AB  - BACKGROUND: Injecting drug users (IDU) are at premature risk of developing
      multimorbidity and mortality from causes commonly observed in the elderly. Ageing
      of the immune system (immune-senescence) can lead to premature morbidity and
      mortality and can be accelerated by chronic viral infections. Here we
      investigated the impact of HCV monoinfection and HIV/HCV coinfection on immune
      parameters in (ex-) IDU. We analyzed telomere length and expression of
      activation, differentiation and exhaustion markers on T cells at baseline (t = 1)
      and at follow-up (t = 2) (median interval 16.9 years) in IDU who were: HCV mono
      infected (n = 21); HIV/HCV coinfected (n = 23) or multiple exposed but uninfected
      (MEU) (n = 8). RESULTS: The median time interval between t = 1 and t = 2 was 16.9
      years. Telomere length within CD4(+) and CD8(+) T cells decreased significantly
      over time in all IDU groups (p <= 0.012). CD4(+) T-cell telomere length in HCV
      mono-infected IDU was significantly reduced compared to healthy donors at t = 1
      (p < 0.008). HIV/HCV coinfected IDU had reduced CD4(+) and CD8(+) T-cell telomere
      lengths (p <= 0.002) to healthy donors i at t = 1. This was related to persistent
      levels of immune activation but not due to increased differentiation of T cells
      over time. Telomere length decrease was observed within all T-cell subsets, but
      mainly found in immature T cells (CD27(+)CD57(+)) (p <= 0.015). CONCLUSIONS: HCV
      mono-infection and HIV/HCV coinfection enhance T-cell immune-senescence. Our data
      suggest that this occurred early during infection, which warrants early treatment
      for both HCV and HIV to reduce immune senescence in later life.

PMID- 27034703
TI  - Physiological mechanisms of dehydration tolerance contribute to the invasion
      potential of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) relative to
      its less widely distributed congeners.
AB  - BACKGROUND: The Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera:
      Tephritidae) is a highly invasive species now with an almost cosmopolitan
      distribution. Two other damaging, polyphagous and closely-related species, the
      marula fruit fly, Ceratitis cosyra (Walker), and the Natal fly, Ceratitis rosa
      Karsch, are not established outside of sub-Saharan Africa. In this study, adult
      water balance traits and nutritional body composition were measured in all three
      species at different temperatures and levels of relative humidity to determine
      whether tolerance of water stress may partially explain their distribution.
      RESULTS: Adult C. capitata exhibited higher desiccation resistance than C. rosa
      but not C. cosyra. Desiccation resistance of C. capitata was associated with
      lower rates of water loss under hot and dry conditions, higher dehydration
      tolerance, and higher lipid reserves that were catabolised during water stress.
      In comparison with C. capitata, C. cosyra and C. rosa lost water at significantly
      higher rates under hot, dry conditions, and did not catabolise lipids or other
      sources of metabolic water during water stress. CONCLUSIONS: These results
      suggest that adult physiological traits permitting higher tolerance of water
      stress play a role in the success of C. capitata, particularly relative to C.
      rosa. The distribution of C. cosyra is likely determined by the interaction of
      temperature with water stress, as well as the availability of suitable hosts for
      larval development.

PMID- 27034704
TI  - How does hearing loss affect the brain?

PMID- 27034705
TI  - Design and methodology of the Geo-social Analysis of Physicians' settlement (GAP
      Study) in Germany.
AB  - BACKGROUND: Unequally distributed disease burdens within populations are well
      known and occur worldwide. They are depending on residents' social status and/or
      ethnic background. Country-specific health care systems - especially the coverage
      and distribution of health care providers - are both a potential cause as well as
      an important solution for health inequalities. METHODS: Registers are built of
      all accredited physicians and psychotherapists within the outpatient care system
      in German metropolises by utilizing the database of the Associations of Statutory
      Health Insurance Physicians. The physicians' practice neighborhood will be
      analyzed under socioeconomic and demographic perspectives. Therefore, official
      city districts' statistics will be assigned to the physicians and
      psychotherapists according to their practice location. Averages of neighborhood
      indicators will be calculated for each specialty. Moreover, advanced studies will
      inspect differences by physicians' gender or practice type. Geo-spatial analyses
      of the intra-city practices distribution will complete the settlement
      characteristics of physicians and psychotherapists within the outpatient care
      system in German metropolises. RESULTS: The project "Geo-social Analysis of
      Physicians' settlement" (GAP) is designed to elucidate gaps of physician coverage
      within the outpatient care system, dependent on neighborhood residents' social
      status or ethnics in German metropolises. CONCLUSION: The methodology of the GAP
      Study enables the standardized investigation of physicians' settlement behavior
      in German metropolises and their inter-city comparisons. The identification of
      potential gaps within the physicians' coverage should facilitate the delineation
      of approaches for solving health care inequality problems.

PMID- 27034706
TI  - Symmetry Analysis of Gait between Left and Right Limb Using Cross-Fuzzy Entropy.
AB  - The purpose of this paper is the investigation of gait symmetry problem by using
      cross-fuzzy entropy (C-FuzzyEn), which is a recently proposed cross entropy that
      has many merits as compared to the frequently used cross sample entropy (C
      SampleEn). First, we used several simulation signals to test its performance
      regarding the relative consistency and dependence on data length. Second, the
      gait time series of the left and right stride interval were used to calculate the
      C-FuzzyEn values for gait symmetry analysis. Besides the statistical analysis, we
      also realized a support vector machine (SVM) classifier to perform the
      classification of normal and abnormal gaits. The gait dataset consists of 15
      patients with Parkinson's disease (PD) and 16 control (CO) subjects. The results
      show that the C-FuzzyEn values of the PD patients' gait are significantly higher
      than that of the CO subjects with a p value of less than 10(-5), and the best
      classification performance evaluated by a leave-one-out (LOO) cross-validation
      method is an accuracy of 96.77%. Such encouraging results imply that the C
      FuzzyEn-based gait symmetry measure appears as a suitable tool for analyzing
      abnormal gaits. 

PMID- 27034707
TI  - Pathogenic Network Analysis Predicts Candidate Genes for Cervical Cancer.
AB  - PURPOSE: The objective of our study was to predicate candidate genes in cervical
      cancer (CC) using a network-based strategy and to understand the pathogenic
      process of CC. METHODS: A pathogenic network of CC was extracted based on known
      pathogenic genes (seed genes) and differentially expressed genes (DEGs) between
      CC and normal controls. Subsequently, cluster analysis was performed to identify
      the subnetworks in the pathogenic network using ClusterONE. Each gene in the
      pathogenic network was assigned a weight value, and then candidate genes were
      obtained based on the weight distribution. Eventually, pathway enrichment
      analysis for candidate genes was performed. RESULTS: In this work, a total of 330
      DEGs were identified between CC and normal controls. From the pathogenic network,
      2 intensely connected clusters were extracted, and a total of 52 candidate genes
      were detected under the weight values greater than 0.10. Among these candidate
      genes, VIM had the highest weight value. Moreover, candidate genes MMP1, CDC45,
      and CAT were, respectively, enriched in pathway in cancer, cell cycle, and
      methane metabolism. CONCLUSION: Candidate pathogenic genes including MMP1, CDC45,
      CAT, and VIM might be involved in the pathogenesis of CC. We believe that our
      results can provide theoretical guidelines for future clinical application.

PMID- 27034709
TI  - Evaluation of Round Window Stimulation Performance in Otosclerosis Using Finite
      Element Modeling.
AB  - Round window (RW) stimulation is a new type of middle ear implant's application
      for treating patients with middle ear disease, such as otosclerosis. However,
      clinical outcomes show a substantial degree of variability. One source of
      variability is the variation in the material properties of the ear components
      caused by the disease. To investigate the influence of the otosclerosis on the
      performance of the RW stimulation, a human ear finite element model including
      middle ear and cochlea was established based on a set of microcomputerized
      tomography section images of a human temporal bone. Three characteristic changes
      of the otosclerosis in the auditory system were simulated in the FE model:
      stapedial annular ligament stiffness enlargement, stapedial abnormal bone growth,
      and partial fixation of the malleus. The FE model was verified by comparing the
      model-predicted results with published experimental measurements. The equivalent
      sound pressure (ESP) of RW stimulation was calculated via comparing the
      differential intracochlear pressure produced by the RW stimulation and the normal
      eardrum sound stimulation. The results show that the increase of stapedial
      annular ligament and partial fixation of the malleus decreases RW stimulation's
      ESP prominently at lower frequencies. In contrast, the stapedial abnormal bone
      growth deteriorates RW stimulation's ESP severely at higher frequencies. 

PMID- 27034708
TI  - Bayesian Inference for Functional Dynamics Exploring in fMRI Data.
AB  - This paper aims to review state-of-the-art Bayesian-inference-based methods
      applied to functional magnetic resonance imaging (fMRI) data. Particularly, we
      focus on one specific long-standing challenge in the computational modeling of
      fMRI datasets: how to effectively explore typical functional interactions from
      fMRI time series and the corresponding boundaries of temporal segments. Bayesian
      inference is a method of statistical inference which has been shown to be a
      powerful tool to encode dependence relationships among the variables with
      uncertainty. Here we provide an introduction to a group of Bayesian-inference
      based methods for fMRI data analysis, which were designed to detect magnitude or
      functional connectivity change points and to infer their functional interaction
      patterns based on corresponding temporal boundaries. We also provide a comparison
      of three popular Bayesian models, that is, Bayesian Magnitude Change Point Model
      (BMCPM), Bayesian Connectivity Change Point Model (BCCPM), and Dynamic Bayesian
      Variable Partition Model (DBVPM), and give a summary of their applications. We
      envision that more delicate Bayesian inference models will be emerging and play
      increasingly important roles in modeling brain functions in the years to come. 

PMID- 27034710
TI  - A Novel Method for the Separation of Overlapping Pollen Species for Automated
      Detection and Classification.
AB  - The identification of pollen in an automated way will accelerate different tasks
      and applications of palynology to aid in, among others, climate change studies,
      medical allergies calendar, and forensic science. The aim of this paper is to
      develop a system that automatically captures a hundred microscopic images of
      pollen and classifies them into the 12 different species from Lagunera Region,
      Mexico. Many times, the pollen is overlapping on the microscopic images, which
      increases the difficulty for its automated identification and classification.
      This paper focuses on a method to segment the overlapping pollen. First, the
      proposed method segments the overlapping pollen. Second, the method separates the
      pollen based on the mean shift process (100% segmentation) and erosion by H
      minima based on the Fibonacci series. Thus, pollen is characterized by its shape,
      color, and texture for training and evaluating the performance of three
      classification techniques: random tree forest, multilayer perceptron, and Bayes
      net. Using the newly developed system, we obtained segmentation results of 100%
      and classification on top of 96.2% and 96.1% in recall and precision using
      multilayer perceptron in twofold cross validation. 

PMID- 27034711
TI  - Dense Trajectories and DHOG for Classification of Viewpoints from Echocardiogram
      Videos.
AB  - In echo-cardiac clinical computer-aided diagnosis, an important step is to
      automatically classify echocardiography videos from different angles and
      different regions. We propose a kind of echocardiography video classification
      algorithm based on the dense trajectory and difference histograms of oriented
      gradients (DHOG). First, we use the dense grid method to describe feature
      characteristics in each frame of echocardiography sequence and then track these
      feature points by applying the dense optical flow. In order to overcome the
      influence of the rapid and irregular movement of echocardiography videos and get
      more robust tracking results, we also design a trajectory description algorithm
      which uses the derivative of the optical flow to obtain the motion trajectory
      information and associates the different characteristics (e.g., the trajectory
      shape, DHOG, HOF, and MBH) with embedded structural information of the
      spatiotemporal pyramid. To avoid "dimension disaster," we apply Fisher's vector
      to reduce the dimension of feature description followed by the SVM linear
      classifier to improve the final classification result. The average accuracy of
      echocardiography video classification is 77.12% for all eight viewpoints and 100%
      for three primary viewpoints. 

PMID- 27034712
TI  - Risk factors for delayed neuro-surgical intervention in patients with acute mild
      traumatic brain injury and intracranial hemorrhage.
AB  - BACKGROUND: Mild traumatic brain injury (TBI) patients with initial traumatic
      intracranial hemorrhage (tICH) and without immediate neuro-surgical intervention
      require close monitoring of their neurologic status. Progressive hemorrhage and
      neurologic deterioration may need delayed neuro-surgical intervention. This study
      aimed to determine the potential risk factors of delayed neuro-surgical
      intervention in mild TBI patients with tICH on admission. METHODS: Three hundred
      and forty patients with mild TBI and tICH who did not need immediate neuro
      surgical intervention on admission were evaluated retrospectively. Their
      demographic information, clinical evaluation, laboratory data, and brain CT was
      reviewed. Delayed neuro-surgical intervention was defined as failure of non
      operative management after initial evaluation. Risk factors of delayed neuro
      surgical intervention on admission were analyzed. RESULTS: Delayed neuro-surgical
      intervention in mild TBI with tICH on initial brain CT accounted for 3.8 %
      (13/340) of all episodes. Higher WBC concentration, higher initial ISS, epidural
      hemorrhage (EDH), higher volume of EDH, midline shift, and skull fracture were
      risk factors of delayed neuro-surgical intervention. The volume of EDH and skull
      fracture is independent risk factors. One cubic centimeter (cm3) increase in EDH
      on initial brain CT increased the risk of delayed neurosurgical intervention by
      16 % (p = 0.011; OR: 1.190, 95 % CI:1.041-1.362). CONCLUSIONS: Mild TBI patients
      with larger volume of EDH have higher risk of delayed neuro-surgical
      interventions after neurosurgeon assessment. Longer and closer neurological
      function monitor and repeated brain image is required for those patients had
      initial larger EDH. A large-scale, multi-centric trial with a bigger study
      population should be performed to validate the findings.

PMID- 27034713
TI  - The global potential for carbon capture and storage from forestry.
AB  - BACKGROUND: Discussions about limiting anthropogenic emissions of CO[Formula: see
      text] often focus on transition to renewable energy sources and on carbon capture
      and storage (CCS) of CO[Formula: see text]. The potential contributions from
      forests, forest products and other low-tech strategies are less frequently
      discussed. Here we develop a new simulation model to assess the global carbon
      content in forests and apply the model to study active annual carbon harvest 100
      years into the future. RESULTS: The numerical experiments show that under a
      hypothetical scenario of globally sustainable forestry the world's forests could
      provide a large carbon sink, about one gigatonne per year, due to enhancement of
      carbon stock in tree biomass. In addition, a large amount of wood, 11.5 GT of
      carbon per year, could be extracted for reducing CO[Formula: see text] emissions
      by substitution of wood for fossil fuels. CONCLUSION: The results of this study
      indicate that carbon harvest from forests and carbon storage in living forests
      have a significant potential for CCS on a global scale.

PMID- 27034714
TI  - Pyrolysis characteristics and kinetics of lignin derived from enzymatic
      hydrolysis residue of bamboo pretreated with white-rot fungus.
AB  - BACKGROUND: The lignocellulose biorefinery based on the sugar platform usually
      focuses on polysaccharide bioconversion, while lignin is only burned for energy
      recovery. Pyrolysis can provide a novel route for the efficient utilization of
      residual lignin obtained from the enzymatic hydrolysis of lignocellulose. The
      pyrolysis characteristics of residual lignin are usually significantly affected
      by the pretreatment process because of structural alteration of lignin during
      pretreatment. In recent years, biological pretreatment using white-rot fungi has
      attracted extensive attention, but there are only few reports on thermal
      conversion of lignin derived from enzymatic hydrolysis residue (EHRL) of the bio
      pretreated lignocellulose. Therefore, the study investigated the pyrolysis
      characteristics and kinetics of EHRL obtained from bamboo pretreated with
      Echinodontium taxodii in order to evaluate the potential of thermal conversion
      processes of EHRL. RESULTS: Fourier transform infrared spectroscopy spectra
      showed that EHRL of bamboo treated with E. taxodii had the typical lignin
      structure, but aromatic skeletal carbon and side chain of lignin were partially
      altered by the fungus. Thermogravimetric analysis indicated that EHRL pyrolysis
      at different heating rates could be divided into two depolymerization stages and
      covered a wide temperature range from 500 to 900 K. The thermal decomposition
      reaction can be well described by two third-order reactions. The kinetics study
      indicated that the EHRL of bamboo treated with white-rot fungus had lower
      apparent activation energies, lower peak temperatures of pyrolysis reaction, and
      higher char residue than the EHRL of raw bamboo. Pyrolysis-gas chromatography
      mass spectrometry (Py-GC/MS) was applied to characterize the fast pyrolysis
      products of EHRL at 600 C. The ratios of guaiacyl-type to syringyl-type
      derivatives yield (G/S) and guaiacyl-type to p-hydroxy-phenylpropane-type
      derivatives yield (G/H) for the treated sample were increased by 33.18 and 25.30
      % in comparison with the raw bamboo, respectively. CONCLUSIONS: The structural
      alterations of lignin during pretreatment can decrease the thermal stability of
      EHRL from the bio-treated bamboo and concentrate the guaiacyl-type derivatives in
      the fast pyrolysis products. Thus, the pyrolysis can be a promising route for
      effective utilization of the enzymatic hydrolysis residue from bio-pretreated
      lignocellulose.

PMID- 27034715
TI  - Engineering of a high lipid producing Yarrowia lipolytica strain.
AB  - BACKGROUND: Microbial lipids are produced by many oleaginous organisms including
      the well-characterized yeast Yarrowia lipolytica, which can be engineered for
      increased lipid yield by up-regulation of the lipid biosynthetic pathway and down
      regulation or deletion of competing pathways. RESULTS: We describe a strain
      engineering strategy centered on diacylglycerol acyltransferase (DGA) gene
      overexpression that applied combinatorial screening of overexpression and
      deletion genetic targets to construct a high lipid producing yeast biocatalyst.
      The resulting strain, NS432, combines overexpression of a heterologous DGA1
      enzyme from Rhodosporidium toruloides, a heterlogous DGA2 enzyme from Claviceps
      purpurea, and deletion of the native TGL3 lipase regulator. These three genetic
      modifications, selected for their effect on lipid production, enabled a 77 %
      lipid content and 0.21 g lipid per g glucose yield in batch fermentation. In fed
      batch glucose fermentation NS432 produced 85 g/L lipid at a productivity of 0.73
      g/L/h. CONCLUSIONS: The yields, productivities, and titers reported in this study
      may further support the applied goal of cost-effective, large -scale microbial
      lipid production for use as biofuels and biochemicals.

PMID- 27034716
TI  - Production of a high-efficiency cellulase complex via beta-glucosidase
      engineering in Penicillium oxalicum.
AB  - BACKGROUND: Trichoderma reesei is a widely used model cellulolytic fungus,
      supplying a highly effective cellulase production system. Recently, the biofuel
      industry discovered filamentous fungi from the Penicillium genus as a promising
      alternative to T. reesei. RESULTS: In our study, we present a systematic over
      expression analysis of nine beta-glucosidase encoding genes in the wild-type
      strain 114-2 of Penicillium oxalicum. We found that the over-expression of BGL1,
      BGL4, or BGL5 significantly enhanced both beta-glucosidase activity and
      hydrolysis efficiency of the enzyme system on filter paper. We utilised two
      strategies to over-express beta-glucosidase in the strain RE-10 that-although
      over-producing cellulase, does so at the cost of the cellulase mixture
      deficiency. The constitutive promoter of gene pde_02864 encoding 40S ribosomal
      protein S8 was used to over-express three beta-glucosidases: BGL1, BGL4, and
      BGL5. We found that all mutants show significantly enhanced levels of beta
      glucosidase at transcriptional, protein, and activity levels. Furthermore, the
      inducible promoter from bgl2 was used to conditionally over-express the beta
      glucosidases BGL1 and BGL4. Surprisingly, this induced expression strategy
      enables significantly improved expression efficiency. The BGL1 over-expressing
      mutant I1-13 particularly improved the beta-glucosidase activity at a factor of
      65-folds, resulting in levels of up to 150 U/ml. All our BGL over-expression
      mutants displayed significant enhancement of cellulolytic ability on both
      microcrystalline cellulose and filter paper. In addition, they substantially
      reduced the enzyme loads in the saccharification of a natural lignocellulose
      material delignified corncob residue (DCCR). The mutant I4-32 with over
      expression of BGL4 achieved the highest glucose yield in the saccharification of
      DCCR at only 25 % enzyme load compared to the parental strain RE-10. CONCLUSIONS:
      In summary, genetically engineering P. oxalicum to significantly improve beta
      glucosidase activity is a potent strategy to substantially boost the hydrolytic
      efficiency of the cellulase cocktail, which will ultimately lead to a
      considerable reduction of cost for biomass-based biofuel.

PMID- 27034717
TI  - Enhanced thermal stability of lichenase from Bacillus subtilis 168 by
      SpyTag/SpyCatcher-mediated spontaneous cyclization.
AB  - BACKGROUND: SpyTag is a peptide that can form an irreversible covalent linkage to
      its 12 kDa partner SpyCatcher via a spontaneous isopeptide bond. Herein, we fused
      SpyTag at the N-terminal of lichenase and SpyCatcher at C-terminal so that the
      termini of lichenase were locked together by the covalent interaction between the
      partners. In addition, an elastin-like polypeptides tag was subsequently attached
      to the C-terminus of SpyCatcher, thereby facilitating the non-chromatographic
      purification of cyclized lichenase. RESULTS: The study showed that the optimum
      temperature of the cyclized lichenase was about 5  degrees C higher in comparison
      to its linear counterpart. Moreover, nearly 80 % of the cyclized lichenase
      activities were retained after 100  degrees C exposure, whereas the linear form
      lost almost all of its activities. Therefore, the cyclized variant displayed a
      significantly higher thermal stability as temperature elevated and was resistant
      to hyperthermal denaturation. Besides, the Km value of the cyclized lichenase
      (7.58 +/- 0.92 mg/mL) was approximately 1.7-fold lower than that of the linear
      one (12.96 +/- 1.93 mg/mL), indicating a higher affinity with substrates.
      CONCLUSIONS: This new SpyTag/SpyCatcher cyclization strategy is deemed as a
      generalized reference for enhancing enzyme stability and can be effectively
      customized to the cyclization of various enzymes, hence a tremendous potential
      for successful application in the biocatalytic conversion of biomass to produce
      fuels and chemicals.

PMID- 27034718
TI  - Microarray testing in clinical diagnosis: an analysis of 5,300 New Zealand
      patients.
AB  - BACKGROUND: The use of Microarray (array CGH) analysis has become a widely
      accepted front-line test replacing G banded chromosome studies for patients with
      an unexplained phenotype. We detail our findings of over 5300 cases. RESULTS: Of
      5369 pre and postnatal samples, copy number variants (CNVs) were detected in 28.3
      %, of which ~40 % were deletions and ~60 % were duplications. 96.8 % of cases
      with a CNV <5 Mb would not have been detected by G banding. At least 4.9 % were
      determined to meet the minimum criteria for a known syndrome. Chromosome 17
      provided the greatest proportion of pathogenic CNVs with 65 % classified as
      (likely) pathogenic. X chromosome CNVs were the most commonly detected accounting
      for 4.2 % of cases, 0.7 % of these being classified as cryptic (likely)
      pathogenic CNVs. CONCLUSIONS: Microarray analysis as a primary testing strategy
      has led to a significant increase in the detection of CNVs (~29 % overall), with
      ~9 % carrying pathogenic CNVs and one syndromic case identified per 20 referred
      patients. We suggest these frequencies are consistent with other heterogeneous
      studies. Conversely, (likely) pathogenic X chromosome CNVs appear to be greater
      compared with previous studies.

PMID- 27034719
TI  - A Framework for 3D Vessel Analysis using Whole Slide Images of Liver Tissue
      Sections.
AB  - Three-dimensional (3D) high resolution microscopic images have high potential for
      improving the understanding of both normal and disease processes where structural
      changes or spatial relationship of disease features are significant. In this
      paper, we develop a complete framework applicable to 3D pathology analytical
      imaging, with an application to whole slide images of sequential liver slices for
      3D vessel structure analysis. The analysis workflow consists of image
      registration, segmentation, vessel cross-section association, interpolation, and
      volumetric rendering. To identify biologically-meaningful correspondence across
      adjacent slides, we formulate a similarity function for four association cases.
      The optimal solution is then obtained by constrained Integer Programming. We
      quantitatively and qualitatively compare our vessel reconstruction results with
      human annotations. Validation results indicate a satisfactory concordance as
      measured both by region-based and distance-based metrics. These results
      demonstrate a promising 3D vessel analysis framework for whole slide images of
      liver tissue sections.

PMID- 27034721
TI  - An update on the use of transdermal oxybutynin in the management of overactive
      bladder disorder.
AB  - Antimuscarinic medications are used to treat nonneurogenic overactive bladder
      refractory to nonpharmacologic therapy. Side effects such as dry mouth,
      constipation, blurred vision, dizziness, and impaired cognition limit the
      tolerability of therapy and are largely responsible for high discontinuation
      rates. Oxybutynin is a potent muscarinic receptor antagonist whose primary
      metabolite after first-pass hepatic metabolism is considered largely responsible
      for its associated anticholinergic side effects. Transdermal administration of
      medications bypasses hepatic processing. Specifically with oxybutynin, whose low
      molecular weight permits transdermal administration, bioavailability of the
      parent drug with oral administration is less than 10%, whereas with transdermal
      delivery is a minimum of 80%. The result has been an improved side effect profile
      in multiple clinical trials with maintained efficacy relative to placebo;
      however, the drug may still be discontinued by patients due to anticholinergic
      side effects and application site reactions. Transdermal oxybutynin is available
      as a patch that is changed every 3-4 days, a gel available in individual sachets,
      or via a metered-dose pump that is applied daily. The transdermal patch was
      briefly available as an over-the-counter medication for adult women, although at
      this time all transdermal formulations are available by prescription only. 

PMID- 27034720
TI  - Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH)
      agonists plus anti-androgen flare protection in advanced prostate cancer: an
      analysis of two randomized controlled trials.
AB  - OBJECTIVES: The objective of this study was to assess differences in efficacy
      outcomes between luteinizing hormone-releasing hormone (LHRH) agonist plus
      antiandrogen (AA) flare protection and monotherapy with the gonadotrophin
      releasing hormone antagonist degarelix in patients with prostate cancer. METHODS:
      Data from 1455 patients were pooled from two prospective, phase III randomized 1
      year clinical trials of degarelix versus LHRH agonist with or without AA. The AA
      bicalutamide was administered at the investigator's discretion. Adjusted hazard
      ratios (HRs) were calculated using a Cox proportional hazards regression model
      and a conditional logistic regression model was used for a case-control analysis
      of odds ratios (ORs). RESULTS: Patients received degarelix monotherapy (n = 972)
      or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific
      antigen progression-free survival (PSA PFS) was improved with degarelix versus
      LHRH agonist + AA (Cox proportional hazards regression model-adjusted HR for PSA
      PFS failure was 0.56 [95% confidence interval (CI) 0.33-0.97, p = 0.038]). To
      compensate for a higher proportion of patients with metastases, Gleason score 7
      10, and PSA >20 ng/ml in the LHRH agonist + AA group, a case-control analysis
      using a conditional logistic regression model was utilized. This resulted in an
      OR for PSA PFS of 0.42 (95% CI 0.20-0.89; p = 0.023) in the overall population,
      and 0.35 (95% CI 0.13-0.96; p = 0.042) in patients with PSA >50 ng/ml at
      baseline, when treated with degarelix versus LHRH agonists + AA. There were a
      small number of deaths, 1.9% with degarelix and 7% with LHRH agonists + AA (case
      control analysis OR = 0.37; p = 0.085). CONCLUSIONS: Degarelix monotherapy
      produced a more favorable effect on PSA PFS outcomes than a LHRH agonist + AA
      flare protection therapy in patients with prostate cancer when a case-control
      analysis was used to compensate for differences between treatment groups.

PMID- 27034722
TI  - Managing chronic bladder diseases with the administration of exogenous
      glycosaminoglycans: an update on the evidence.
AB  - Although the pathophysiology of acute chronic cystitis and other 'sensory'
      disorders, i.e. painful bladder syndrome (PBS) or interstitial cystitis (IC),
      often remains multifactorial, there is a wide consensus that such clinical
      conditions may arise from a primary defective urothelium lining or from damaged
      glycosaminoglycans (GAGs). A 'cascade' of events starting from GAG injury, which
      fails to heal, may lead to chronic bladder epithelial damage and neurogenic
      inflammation. To restore the GAG layer is becoming the main aim of new therapies
      for the treatment of chronic cystitis and PBS/IC. Preliminary experiences with
      GAG replenishment for different pathological conditions involving the lower
      urinary tract have been reported. There is a range of commercially available
      intravesical formulations of these components, alone or in combination.
      Literature evidence shows that exogenous intravesical hyaluronic acid markedly
      reduces recurrences of urinary tract infections (UTIs). Patients treated with
      exogenous GAGs have fewer UTI recurrences, a longer time to recurrence and a
      greater improvement in quality of life. Exogenous intravesical GAGs have been
      used for the treatment of PBS/IC. Despite the limitations of most of the studies,
      findings confirmed the role of combination therapy with hyaluronic acid and
      chondroitin sulfate as a safe and effective option for the treatment of PBS/IC.
      To prevent and/or treat radiotherapy and chemotherapy induced cystitis, GAG
      replenishment therapy has been used showing preliminary encouraging results. The
      safety profile of exogenous GAGs has been reported to be very favourable, without
      adverse events of particular significance. 

PMID- 27034723
TI  - A review of the efficacy and safety of mirodenafil in the management of erectile
      dysfunction.
AB  - Erectile dysfunction (ED) is a common disorder that can jeopardize quality of
      life and the partnership of patients and their sexual partners. The advent of
      oral phosphodiesterase type 5 inhibitors (PDE5Is) has revolutionized a treatment
      for ED, and they are recognized as the first-line therapy for ED, regardless of
      its etiology. Mirodenafil, a second-generation PDE5I, has biochemical profiles
      such as high affinity for PDE5 and high selectivity for PDE5 over other PDE
      isoforms, compared to other existing PDE5Is such as sildenafil, vardenafil and
      tadalafil. Available evidence has suggested that doses of 50 and 100 mg
      mirodenafil effectively improve ED [with improvements in the erectile function
      domain of the International Index of Erectile Function (IIEF-EF) scores, positive
      responses to questions 2 of the Sexual Encounter Profiles (SEP2) and questions 3
      of the Sexual Encounter Profiles (SEP3): 7.6-11.6 points, 27.72-38.98% and 44.20
      67.33%, respectively] in a broad range of patient populations with ED of a
      variety of underlying etiologies, severities and ages, without any serious
      treatment-related adverse effects. In the treatment of diabetic ED, a
      traditionally difficult-to-treat population, 100 mg mirodenafil has been reported
      to offer favorable efficacy (with improvements in the IIEF-EF scores, and
      positive responses to the SEP2 and the SEP3: 9.3 points, 36.1% and 61.8%,
      respectively) and tolerability (mild adverse effects of less than 19.6%), which
      are comparable with results from clinical studies on other PDE5Is. Mirodenafil
      appears to be effective, safe and well tolerated in men with both ED and
      hypertension or lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia
      (BPH) who are taking concomitant antihypertensive medications or alpha1-blockers.
      Furthermore, recent evidence has indicated that mirodenafil may be a potential
      option for chronic dosing in the treatment of ED despite its short half-life (T
      1/2). Most of the available clinical studies have reported that adverse effects
      (up to 53.7%) caused by 50 and 100 mg mirodenafil are mild or moderate in
      severity, with headache (1.8-14.8%) and flushing (6.7-24.1%) being the most
      common. Due to the pharmacodynamic profiles of mirodenafil, its tolerability is
      expected to be somewhat better than those of the other PDE5Is. However, further
      well designed studies with larger cohorts of different ethnicities, flexible
      dosing schedules and long-term follow up are necessary to confirm the favorable
      efficacy and tolerability profiles of mirodenafil for the treatment of ED. 

PMID- 27034724
TI  - Androgen deprivation therapy and cardiovascular disease: what is the linking
      mechanism?
AB  - The past decade has brought increased awareness of the potential adverse effects
      of androgen deprivation therapy (ADT) in men with prostate cancer. Arguably the
      most important and controversial of these is the increased risk of cardiovascular
      morbidity and mortality. Although multiple observational studies have shown that
      men treated with ADT are at increased risk of developing atherosclerotic
      cardiovascular disease, our understanding of the biological mechanisms that might
      underlie this phenomenon is still evolving. In this review, we discuss some of
      the mechanisms that have been proposed to date, including ADT-induced metabolic
      changes that promote the development and progression of atherosclerotic plaques
      as well as direct local effects of hormonal factors on plaque growth, rupture and
      thrombosis. 

PMID- 27034725
TI  - The role of neoadjuvant therapy in the management of locally advanced renal cell
      carcinoma.
AB  - In the past decade, the armamentarium of targeted therapy agents for the
      treatment of metastatic renal cell carcinoma (RCC) has significantly increased.
      Improvements in response rates and survival, with more manageable side effects
      compared with interleukin 2/interferon immunotherapy, have been reported with the
      use of targeted therapy agents, including vascular endothelial growth factor
      (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib,
      axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and
      temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines
      reflect these new therapeutic approaches with treatments based on risk category,
      histology and line of therapy in the metastatic setting. However, while radical
      nephrectomy remains the standard of care for locally advanced RCC, the migration
      and use of these agents from salvage to the neoadjuvant setting for large
      unresectable masses, high-level venous tumor thrombus involvement, and patients
      with imperative indications for nephron sparing has been increasingly described
      in the literature. Several trials have recently been published and some are still
      recruiting patients in the neoadjuvant setting. While the results of these trials
      will inform and guide the use of these agents in the neoadjuvant setting, there
      still remains a considerable lack of consensus in the literature regarding the
      effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of
      this review is to shed light on the current body of evidence with regards to the
      use of neoadjuvant treatments in the setting of locally advanced RCC. 

PMID- 27034726
TI  - 'Mini, ultra, micro' - nomenclature and cost of these new minimally invasive
      percutaneous nephrolithotomy (PCNL) techniques.
AB  - New minimally invasive percutaneous nephrolithotomy (PCNL) techniques have
      changed the management of renal stones. We discuss the technological advances in
      PCNL and explain the meaning, requirements and set up costs for each of these
      'newer' techniques. 

PMID- 27034727
TI  - An update on the role of testosterone replacement therapy in the management of
      hypogonadism.
AB  - While US testosterone prescriptions have tripled in the last decade with lower
      trends in Europe, debate continues over the risks, benefits and appropriate use
      of testosterone replacement therapy (TRT). Some authors blame advertising and the
      availability of more convenient formulations whilst other have pointed out that
      the routine testing of men with erectile dysfunction (a significant marker of
      cardiovascular risk) and those with diabetes would inevitably increase the
      diagnosis of hypogonadism and lead to an increase in totally appropriate
      prescribing. They commented that this was merely an appropriate correction of
      previous underdiagnosis and undertreatment by adherence to evidence-based
      guidelines. Urologists and primary care physicians are the most frequent
      initiators of TRT, usually for erectile dysfunction. Benefits are clearly
      established for sexual function, increase in lean muscle mass and strength, mood
      and cognitive function, with possible reduction in frailty and osteoporosis.
      There remains no evidence that TRT is associated with increased risk of prostate
      cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate
      and continue therapy is often decided by urologists. The cardiovascular issues
      associated with TRT have been clarified by recent studies showing clearly that
      therapy associated with clear rise in testosterone levels are associated with
      reduced mortality. Studies reporting to show increased risk have been subject to
      flawed designs with inadequate baseline diagnosis and follow-up testing.
      Effectively they have compared nontreated patients with undertreated or on
      compliant subjects involving a range of different therapy regimens. Recent
      evidence suggests long acting injections may be associated with decreased
      cardiovascular risk but the transdermal route may be associated with potentially
      relatively greater risk because of conversion to dihydrotestosterone by the
      effect of 5alpha reductase in skin. The multiple effects of TRT may add up to a
      considerable benefit to the patient that might be underestimated by the physician
      primarily concerned with his own specialty. This paper will attempt to identify
      who should be treated, and how they should be treated safely to achieve best
      outcomes, based on a comprehensive MEDLINE and EMBASE and Cochrane searches on
      hypogonadism, TRT and cardiovascular safety from May 2005 to May 2015. This
      revealed 1714 papers with 52 clinical trials and 32 placebo-controlled
      randomized, controlled trials. 

PMID- 27034729
TI  - A School-Based Mindfulness Pilot Study for Ethnically Diverse At-Risk
      Adolescents.

PMID- 27034728
TI  - Global histone modification profiling reveals the epigenomic dynamics during
      malignant transformation in a four-stage breast cancer model.
AB  - BACKGROUND: Epigenetic regulation has emerged to be the critical steps for
      tumorigenesis and metastasis. Multiple histone methyltransferase and demethylase
      have been implicated as tumor suppressors or oncogenes recently. But the key
      epigenomic events in cancer cell transformation still remain poorly understood.
      METHODS: A breast cancer transformation model was established via stably
      expressing three oncogenes in primary breast epithelial cells. Chromatin
      immunoprecipitation followed by the next-generation sequencing of histone
      methylations was performed to determine epigenetic events during transformation.
      Western blot, quantitative RT-PCR, and immunostaining were used to determine gene
      expression in cells and tissues. RESULTS: Histones H3K9me2 and me3, two
      repressive marks of transcription, decrease in in vitro breast cancer cell model
      and in vivo clinical tissues. A survey of enzymes related with H3K9 methylation
      indicated that KDM3A/JMJD1A, a demethylase for H3K9me1 and me2, gradually
      increases during cancer transformation and is elevated in patient tissues.
      KDM3A/JMJD1A deficiency impairs the growth of tumors in nude mice and transformed
      cell lines. Genome-wide ChIP-seq analysis reveals that the boundaries of
      decreased H3K9me2 large organized chromatin K9 modifications (LOCKs) are enriched
      with cancer-related genes, such as MYC and PAX3. Further studies show that
      KDM3A/JMJD1A directly binds to these oncogenes and regulates their transcription
      by removing H3K9me2 mark. CONCLUSIONS: Our study demonstrates reduction of
      histones H3K9 me2 and me3, and elevation of KDM3A/JMJD1A as important events for
      breast cancer, and illustrates the dynamic epigenomic mechanisms during breast
      cancer transformation.

PMID- 27034730
TI  - Cross-validation and Peeling Strategies for Survival Bump Hunting using Recursive
      Peeling Methods.
AB  - We introduce a framework to build a survival/risk bump hunting model with a
      censored time-to-event response. Our Survival Bump Hunting (SBH) method is based
      on a recursive peeling procedure that uses a specific survival peeling criterion
      derived from non/semi-parametric statistics such as the hazards-ratio, the log
      rank test or the Nelson--Aalen estimator. To optimize the tuning parameter of the
      model and validate it, we introduce an objective function based on survival or
      prediction-error statistics, such as the log-rank test and the concordance error
      rate. We also describe two alternative cross-validation techniques adapted to the
      joint task of decision-rule making by recursive peeling and survival estimation.
      Numerical analyses show the importance of replicated cross-validation and the
      differences between criteria and techniques in both low and high-dimensional
      settings. Although several non-parametric survival models exist, none addresses
      the problem of directly identifying local extrema. We show how SBH efficiently
      estimates extreme survival/risk subgroups unlike other models. This provides an
      insight into the behavior of commonly used models and suggests alternatives to be
      adopted in practice. Finally, our SBH framework was applied to a clinical
      dataset. In it, we identified subsets of patients characterized by clinical and
      demographic covariates with a distinct extreme survival outcome, for which
      tailored medical interventions could be made. An R package PRIMsrc (Patient Rule
      Induction Method in Survival, Regression and Classification settings) is
      available on CRAN (Comprehensive R Archive Network) and GitHub.

PMID- 27034731
TI  - Effect of Blueberry Anthocyanins Malvidin and Glycosides on the Antioxidant
      Properties in Endothelial Cells.
AB  - The objective of this research was to survey the antioxidant functional role of
      the main anthocyanins of blueberries in endothelial cells. Changes on the
      reactive oxygen species (ROS), xanthine oxidase-1 (XO-1), superoxide dismutase
      (SOD), and heme oxygenase-1 (HO-1) in cells of malvidin and the two glycosides
      were investigated. The results showed that these anthocyanins decreased the
      levels of ROS and XO-1 but increased the levels of SOD and HO-1. Glycosides
      improved the antioxidant capacity of malvidin to a great extent. The changes in
      the antioxidant properties of malvidin-3-glucoside were more pronounced than
      malvidin-3-galactoside. Variation in levels of malvidin-3-glucoside and malvidin
      3-galactoside had a significant impact on antioxidant properties to different
      extents. It indicates that blueberries are a good resource of anthocyanins, which
      can protect cells from oxidative deterioration and use blueberry as a potential
      functional food to prevent diseases related to oxidative stress. 

PMID- 27034732
TI  - Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against
      Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and
      Promoting GSK-3beta Phosphorylation.
AB  - The opening of mitochondrial permeability transition pore (mPTP) is a major cause
      of cell death in ischemia reperfusion injury. Based on our pilot experiments,
      plant natural product formononetin enhanced the survival of rat cardiomyocyte
      H9c2 cells during oxygen glucose deprivation (OGD) and reoxygenation. For
      mechanistic studies, we focused on two major cellular factors, namely, reactive
      oxygen species (ROS) and glycogen synthase kinase 3beta (GSK-3beta), in the
      regulation of mPTP opening. We found that formononetin suppressed the formation
      of ROS and superoxide in a concentration-dependent manner. Formononetin also
      rescued OGD/reoxygenation-induced loss of mitochondrial membrane integrity.
      Further studies suggested that formononetin induced Akt activation and GSK-3beta
      (Ser9) phosphorylation, thereby reducing GSK-3beta activity towards mPTP opening.
      PI3K and PKC inhibitors abolished the effects of formononetin on mPTP opening and
      GSK-3beta phosphorylation. Immunoprecipitation experiments further revealed that
      formononetin increased the binding of phosphor-GSK-3beta to adenine nucleotide
      translocase (ANT) while it disrupted the complex of ANT with cyclophilin D.
      Moreover, immunofluorescence revealed that phospho-GSK-3beta (Ser9) was mainly
      deposited in the space between mitochondria and cell nucleus. Collectively, these
      results indicated that formononetin protected cardiomyocytes from
      OGD/reoxygenation injury via inhibiting ROS formation and promoting GSK-3beta
      phosphorylation. 

PMID- 27034733
TI  - Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes
      in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined
      Extract of Purple Rice and Silkworm Pupae.
AB  - Due to the crucial role of oxidative stress on the pathophysiology of autism and
      the concept of synergistic effect, the benefit of the combined extract of purple
      rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we
      aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress
      status, and histopathological change of cerebellum in valproic acid (VPA) rat
      model of autism. VPA was injected on postnatal day (PND) 14 and the animals were
      orally given AP1 at doses of 50, 100, and 200 mg.kg(-1) BW between PND 14 and PND
      40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus
      maze, learning, memory, and social behavior tests. Oxidative stress and the
      histological change in the cerebellum were assessed at the end of study. AP1
      treated rats improved behaviors in all tests except that in hot-plate test. The
      improvement of oxidative stress and Purkinje cell loss was also observed in the
      cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced
      autism-like behaviors by improving oxidative stress and Purkinje cell loss.
      Further research is required to identify the active ingredients in AP1 and gender
      difference effect. 

PMID- 27034736
TI  - Antioxidant and DNA Repair Stimulating Effect of Extracts from Transformed and
      Normal Roots of Rhaponticum carthamoides against Induced Oxidative Stress and DNA
      Damage in CHO Cells.
AB  - Rhaponticum carthamoides has a long tradition of use in Siberian folk medicine.
      The roots and rhizomes of this species are used in various dietary supplements or
      nutraceutical preparations to increase energy level or eliminate physical
      weakness. This is the first report to reveal the protective and DNA repair
      stimulating abilities of R. carthamoides root extracts in Chinese hamster ovary
      (CHO) cells exposed to an oxidative agent. Both transformed root extract (TR
      extract) and extract of soil-grown plant roots (NR extract) may be responsible
      for stimulating CHO cells to repair oxidatively induced DNA damage, but CHO cells
      stimulated with extract from the transformed roots demonstrated significantly
      stronger properties than cells treated with the soil-grown plant root extract.
      These differences in biological activity may be attributed to the differences in
      the content of phenolic compounds in these root extracts. Preincubation of the
      CHO cells with TR and NR extracts showed an increase in gene expression and
      protein levels of catalase (CAT) and superoxide dismutase (SOD2). R. carthamoides
      may possess antioxidant properties that protect CHO cells against oxidative
      stress. 

PMID- 27034735
TI  - Ameliorative Effects of Antioxidants on the Hippocampal Accumulation of
      Pathologic Tau in a Rat Model of Blast-Induced Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) can lead to early onset dementia and other related
      neurodegenerative diseases. We previously demonstrated that damage to the central
      auditory pathway resulting from blast-induced TBI (bTBI) could be significantly
      attenuated by a combinatorial antioxidant treatment regimen. In the current
      study, we examined the localization patterns of normal Tau and the potential
      blast-induced accumulation of neurotoxic variants of this microtubule-associated
      protein that are believed to potentiate the neurodegenerative effects associated
      with synaptic dysfunction in the hippocampus following three successive blast
      overpressure exposures in nontransgenic rats. We observed a marked increase in
      the number of both hyperphosphorylated and oligomeric Tau-positive hilar mossy
      cells and somatic accumulation of endogenous Tau in oligodendrocytes in the
      hippocampus. Remarkably, a combinatorial regimen of 2,4-disulfonyl alpha-phenyl
      tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) resulted in striking
      reductions in the numbers of both mossy cells and oligodendrocytes positively
      labeled for these pathological Tau immunoreactivity patterns in response to bTBI.
      This treatment strategy represents a promising therapeutic approach for
      simultaneously reducing or eliminating both primary auditory injury and
      nonauditory changes associated with bTBI-induced hippocampal neurodegeneration. 

PMID- 27034734
TI  - The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell
      Death: The Role of ATP Synthase.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) targeting
      mitochondria are major causative factors in disease pathogenesis. The
      mitochondrial permeability transition pore (PTP) is a mega-channel modulated by
      calcium and ROS/RNS modifications and it has been described to play a crucial
      role in many pathophysiological events since prolonged channel opening causes
      cell death. The recent identification that dimers of ATP synthase form the PTP
      and the fact that posttranslational modifications caused by ROS/RNS also affect
      cellular bioenergetics through the modulation of ATP synthase catalysis reveal a
      dual function of these modifications in the cells. Here, we describe mitochondria
      as a major site of production and as a target of ROS/RNS and discuss the
      pathophysiological conditions in which oxidative and nitrosative modifications
      modulate the catalytic and pore-forming activities of ATP synthase. 

PMID- 27034737
TI  - Protective Effect of Decursin Extracted from Angelica gigas in Male Infertility
      via Nrf2/HO-1 Signaling Pathway.
AB  - Higher testicular temperature results in altered spermatogenesis due to heat
      related oxidative stress. We examined the effects of decursin extracted from
      Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism
      induced infertility rat model. TM3 Leydig cell viability was measured based on
      oxidative stress according to treatment. Either distilled water or AG 400 mg/kg
      of A. gigas extract was administered orally for 4 weeks after unilateral
      cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control
      group and six rats from treatment group were sacrificed. Testicular weight, semen
      quality, antioxidant activities, nuclear factor erythroid 2-related factor 2
      (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed.
      Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress
      in a dose-dependent manner, (2) improved the mean weight of the cryptorchid
      testis, (3) maintained sperm counts, motility, and spermatogenic cell density,
      (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels
      of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme
      oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study
      suggests that decursin extracted from A. gigas is a supplemental agent that can
      reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat
      experimentally induced unilateral cryptorchidism and may improve cryptorchidism
      induced infertility. 

PMID- 27034738
TI  - Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its
      Phosphorylation by p (72) Syk.
AB  - In erythrocytes, the regulation of the redox sensitive Tyr phosphorylation of
      band 3 and its functions are still partially defined. A role of band 3 oxidation
      in regulating its own phosphorylation has been previously suggested. The current
      study provides evidences to support this hypothesis: (i) in intact erythrocytes,
      at 2 mM concentration of GSH, band 3 oxidation, and phosphorylation, Syk
      translocation to the membrane and Syk phosphorylation responded to the same
      micromolar concentrations of oxidants showing identical temporal variations; (ii)
      the Cys residues located in the band 3 cytoplasmic domain are 20-fold more
      reactive than GSH; (iii) disulfide linked band 3 cytoplasmic domain docks Syk
      kinase; (iv) protein Tyr phosphatases are poorly inhibited at oxidant
      concentrations leading to massive band 3 oxidation and phosphorylation. We also
      observed that hemichromes binding to band 3 determined its irreversible oxidation
      and phosphorylation, progressive hemolysis, and serine hyperphosphorylation of
      different cytoskeleton proteins. Syk inhibitor suppressed the phosphorylation of
      band 3 also preventing serine phosphorylation changes and hemolysis. Our data
      suggest that band 3 acts as redox sensor regulating its own phosphorylation and
      that hemichromes leading to the protracted phosphorylation of band 3 may trigger
      a cascade of events finally leading to hemolysis. 

PMID- 27034739
TI  - Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products
      from Grapes.
AB  - Advanced age is associated with increased incidence of a variety of chronic
      disease states which share oxidative stress and inflammation as causative role
      players. Furthermore, data point to a role for both cumulative oxidative stress
      and low grade inflammation in the normal ageing process, independently of
      disease. Therefore, arguably the best route with which to address premature
      ageing, as well as age-associated diseases such as diabetes, cardiovascular
      disease, and dementia, is preventative medicine aimed at modulation of these two
      responses, which are intricately interlinked. In this review, we provide a
      detailed account of the literature on the communication of these systems in the
      context of ageing, but with inclusion of relevant data obtained in other models.
      In doing so, we attempted to more clearly elucidate or identify the most probable
      cellular or molecular targets for preventative intervention. In addition, given
      the absence of a clear pharmaceutical solution in this context, together with the
      ever-increasing consumer bias for natural medicine, we provide an overview of the
      literature on grape (Vitis vinifera) derived products, for which beneficial
      effects are consistently reported in the context of both oxidative stress and
      inflammation. 

PMID- 27034740
TI  - DNA Tumor Viruses and Cell Metabolism.
AB  - Viruses play an important role in cancerogenesis. It is estimated that
      approximately 20% of all cancers are linked to infectious agents. The viral genes
      modulate the physiological machinery of infected cells that lead to cell
      transformation and development of cancer. One of the important adoptive responses
      by the cancer cells is their metabolic change to cope up with continuous
      requirement of cell survival and proliferation. In this review we will focus on
      how DNA viruses alter the glucose metabolism of transformed cells. Tumor DNA
      viruses enhance "aerobic" glycolysis upon virus-induced cell transformation,
      supporting rapid cell proliferation and showing the Warburg effect. Moreover,
      viral proteins enhance glucose uptake and controls tumor microenvironment,
      promoting metastasizing of the tumor cells. 

PMID- 27034742
TI  - Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to
      Different Processing Conditions in Human Lung Carcinoma Cells.
AB  - Lung cancer is a common malignancy in men and the second leading cause of cancer
      related mortality in men in the western world. Phenolic cocoa ingredients have a
      strong antioxidative activity and the potential to have a protective effect
      against cancer. In the present study, we have evaluated the influence of cocoa
      beans subjected to different processing conditions on cell viability and
      apoptosis of human lung cancer cells (A549). We measured the viability of lung
      cells treated with cocoa beans, unroasted slates (US), roasted slates (RS),
      unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for
      24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells
      after treatment with cocoa bean extracts. Flow cytometer analysis revealed that
      cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to
      twofold increase of apoptotic cells when compared to the control group. Taken
      together, the present study suggests that cocoa beans may have a protective
      effect against lung cancer. 

PMID- 27034741
TI  - Overview of Alzheimer's Disease and Some Therapeutic Approaches Targeting Abeta
      by Using Several Synthetic and Herbal Compounds.
AB  - Alzheimer's disease (AD) is a complex age-related neurodegenerative disease. In
      this review, we carefully detail amyloid-beta metabolism and its role in AD. We
      also consider the various genetic animal models used to evaluate therapeutics.
      Finally, we consider the role of synthetic and plant-based compounds in
      therapeutics. 

PMID- 27034744
TI  - Studies of the Effectiveness of Bisphosphonate and Vanadium-Bisphosphonate
      Compounds In Vitro against Axenic Leishmania tarentolae.
AB  - Leishmaniasis is a disease that is a significant problem for people, especially
      in tropical regions of the world. Current drug therapies to treat the disease are
      expensive, not very effective, and/or of significant side effects. A series of
      alkyl bisphosphonate compounds and one amino bisphosphonate compound, as well as
      alendronate and zoledronate, were tested as potential agents against Leishmania
      tarentolae. Also, two polyoxometalates (POMs) with nitrogen-containing
      bisphosphonate ligands, vanadium/alendronate (V5(Ale)2) and vanadium/zoledronate
      (V3(Zol)3), were tested against L. tarentolae and compared to the results of the
      alendronate and zoledronate ligands alone. Of the compounds evaluated in this
      study, the V5(Ale)2 and V3(Zol)3 complexes were most effective in inhibiting the
      growth of L. tarentolae. The V5(Ale)2 complex had a larger impact on cell growth
      than either alendronate or orthovanadate alone, whereas zoledronate itself has a
      significant effect on cell growth, which may contribute to the activity of the
      V3(Zol)3 complex. 

PMID- 27034743
TI  - Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells
      from a Diabetic Rat Model.
AB  - Diabetes affects more than 330 million people worldwide and causes elevated
      cardiovascular disease risk. Mitochondria are critical for vascular function,
      generate cellular reactive oxygen species (ROS), and are perturbed by diabetes,
      representing a novel target for therapeutics. We hypothesized that adaptive
      mitochondrial plasticity in response to nutrient stress would be impaired in
      diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated
      decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta
      of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the
      Wistar control rat were exposed to high glucose (25 mM). At baseline,
      significantly greater nitric oxide evolution, ROS production, and respiratory
      control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose,
      expression of phosphorylated eNOS, uncoupled respiration, and expression of
      mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs
      (p < 0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs
      (p < 0.05) with no change in the GK beyond elevated baseline concentrations.
      Baseline comparisons show persistent metabolic perturbations in a diabetes
      phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in
      eNOS and mitochondrial function and disrupted mitochondrial plasticity,
      illustrating eNOS and mitochondria as potential therapeutic targets. 

PMID- 27034745
TI  - Impact of Continuous Erythropoietin Receptor Activator on Selected Biomarkers of
      Cardiovascular Disease and Left Ventricle Structure and Function in Chronic
      Kidney Disease.
AB  - Background. Cardiovascular morbidity and mortality are very high in patients with
      chronic kidney disease (CKD). The purpose of this study is to evaluate the impact
      of continuous erythropoietin receptor activator (CERA) on selected biomarkers of
      cardiovascular disease, left ventricle structure, and function in CKD. Material
      and Methods. Peripheral blood was collected from 25 CKD patients before and after
      CERA treatment and 20 healthy subjects. In serum samples, we assessed
      inflammatory markers (IL-1beta, TNF-RI, TNF-RII, sFas, sFasL, MMP-9, TIMP-1, and
      TGF-beta1), endothelial dysfunction markers (sE-selectin, sICAM-1, and sVCAM-1),
      and volume-related marker (NT-proBNP). All subjects underwent echocardiography
      and were evaluated for selected biochemical parameters (Hb, creatinine, and CRP).
      Results. Evaluated biomarkers and echocardiographic parameters of left ventricle
      structure were significantly increased but left ventricle EF was significantly
      decreased in CKD patients compared to controls. After CERA treatment, we observed
      a significant increase of Hb and left ventricle EF and a significant decrease of
      NT-proBNP and MMP-9. There was a significant negative correlation between Hb and
      TNF-RI, sICAM-1, and IL-1beta. Conclusions. Our results indicate that selected
      biomarkers related to cardiovascular risk are significantly increased in CKD
      patients compared to controls. CERA treatment has anti-inflammatory action,
      diminishes endothelial dysfunction, and improves left ventricle function in these
      patients. 

PMID- 27034746
TI  - Crystal fingerprinting: elucidating the crystals of Cheddar, Parmigiano-Reggiano,
      Gouda, and soft washed-rind cheeses using powder x-ray diffractometry.
AB  - Crystals in cheese may be considered defects or positive features, depending on
      the variety and mode of production (industrial, artisanal). Powder x-ray
      diffractometry (PXRD) offers a simple means to identify and resolve complex
      combinations of crystals that contribute to cheese characteristics. The objective
      of the present research was to demonstrate the application of PXRD to study
      crystals from a range of different cheese types, specifically Cheddar, Parmigiano
      Reggiano, Gouda, and soft washed-rind (smear ripened) cheeses. In studies of
      Parmigiano-Reggiano and long-aged Gouda, PXRD has confirmed that hard (crunchy)
      crystals that form abundantly within these cheeses consist of tyrosine.
      Furthermore, PXRD has tentatively identified the presence of an unusual form of
      crystalline leucine in large (up to 6 mm in diameter) spherical entities, or
      "pearls", that occur abundantly in 2-year-old Parmigiano Reggiano and long-aged
      Gouda cheeses, and on the surface of rindless hard Italian-type cheese. Ongoing
      investigations into the nature of these "pearls" are providing new insight into
      the roles that crystals play in the visual appearance and texture of long-aged
      cheeses. Crystals also sometimes develop profusely in the eyes of long-aged
      Gouda, which have been shown by PXRD to consist of tyrosine and the
      aforementioned presumptive form of crystalline leucine. Finally, crystals have
      been shown by PXRD to form in the smears of soft washed-rind cheeses. These
      crystals may be associated in some cheeses with gritty mouth feel and with zonal
      body softening that occurs during ripening. Heightened interest in artisanal
      cheeses highlights the need to better understand crystals and their contributions
      to cheese characteristics.

PMID- 27034747
TI  - Reduction of aerobic and lactic acid bacteria in dairy desludge using an
      integrated compressed CO2 and ultrasonic process.
AB  - Current treatment routes are not suitable to reduce and stabilise bacterial
      content in some dairy process streams such as separator and bactofuge desludges
      which currently present a major emission problem faced by dairy producers. In
      this study, a novel method for the processing of desludge was developed. The new
      method, elevated pressure sonication (EPS), uses a combination of low frequency
      ultrasound (20 kHz) and elevated CO2 pressure (50 to 100 bar). Process conditions
      (pressure, sonicator power, processing time) were optimised for batch and
      continuous EPS processes to reduce viable numbers of aerobic and lactic acid
      bacteria in bactofuge desludge by >=3-log fold. Coagulation of proteins present
      in the desludge also occurred, causing separation of solid (curd) and liquid
      (whey) fractions. The proposed process offers a 10-fold reduction in energy
      compared to high temperature short time (HTST) treatment of milk.

PMID- 27034748
TI  - Effect of retention design of artificial teeth and implant-supported titanium CAD
      CAM structures on fracture resistance.
AB  - BACKGROUND: For implant-supported hybrid prostheses, high mastication forces and
      reduced acrylic resin thickness over a metal substructure often cause failures
      arising from tooth or resin fractures. To assay fracture resistance of artificial
      teeth and resin in implant-supported hybrid prostheses in relation to the
      titanium structure and retention design supporting teeth. MATERIAL AND METHODS:
      40 specimens bearing incisors were divided into four groups according to the
      titanium structure supporting the teeth and the type of load force applied: Group
      I (Control; n=10): Application of static loading to ten incisors set over a metal
      structure with internal retention. Group II (Control; n=10): Application of
      static loading to ten incisors set over a metal structure with external
      retention. The remaining study specimens (n=20) were subjected to 120,000
      masticatory and thermal cycles in a chewing simulator. Afterwards, static loading
      was applied until the point of fracture using an Instron machine. Group III
      (Study; n=10): Application of dynamic and static loading to ten incisors set over
      a metal structure with internal retention. Group IV (Study; n=10): Application of
      dynamic and static loading to ten incisors set over a metal structure with
      external retention. Data obtained for the four groups was analyzed and compared,
      determining the type of fracture (cohesive or adhesive) using a reflected light
      microscope. RESULTS: Statistical analysis confirmed that there were significant
      differences in fracture resistance between the four groups. External retention
      was found to have more fracture resistance than the internal retention.
      CONCLUSIONS: Hybrid prostheses with titanium substructures and external retention
      obtained significantly better results than samples with internal retention. KEY
      WORDS: Chewing simulator, thermocycler, fatigue, implant-supported hybrid
      prosthesis, acrylic teeth, fracture, metal structure design.

PMID- 27034749
TI  - Use of leukocyte and platelet-rich fibrin (L-PRF) in periodontally accelerated
      osteogenic orthodontics (PAOO): Clinical effects on edema and pain.
AB  - BACKGROUND: Demand for shorter treatment time is common in orthodontic patients.
      Periodontally Accelerated Osteogenic Orthodontics (PAOO) is a somewhat new
      surgical procedure which allows faster tooth movement via combining orthodontic
      forces with corticotomy and grafting of alveolar bone plates. Leukocyte and
      Platelet-Rich Fibrin (L-PRF) possess hard- and soft-tissue healing properties.
      Further, evidence of pain-inhibitory and anti-inflammatory potential is growing.
      Therefore, this study explores the feasibility, intra- and post-operative effects
      of using L-PRF in PAOO in terms of post-operative pain, inflammation, infection
      and post-orthodontic stability. MATERIAL AND METHODS: A pilot prospective
      observational study involving a cohort of 11 patients was carried out. A Wilcko's
      modified PAOO technique with L-PRF (incorporated into the graft and as covering
      membrane) was performed with informed consent. Post-surgical pain, inflammation
      and infection were recorded for 10 days post-operatively, while the overall
      orthodontic treatment and post-treatment stability were followed up to 2 years.
      RESULTS: Accelerated wound healing with no signs of infection or adverse
      reactions was evident. Post-surgical pain was either "mild" (45.5%) or "moderate"
      (54.5%). Immediate post-surgical inflammation was either "mild" (89.9%) or
      "moderate" (9.1%). Resolution began on day 4 where most patients experienced
      either "mild" or no inflammation (72.7% and 9.1%, respectively). Complete
      resolution was achieved in all patients by day 8. The average orthodontic
      treatment time was 9.3 months. All cases were deemed stable for 2 years.
      CONCLUSIONS: L-PRF is simple and safe to use in PAOO. Combination with
      traditional bone grafts potentially accelerates wound healing and reduces post
      surgical pain, inflammation, infection without interfering with tooth movement
      and/or post-orthodontic stability, over a 2 years period; thus alleviating the
      need for analgesics and anti-inflammatory medications. KEY WORDS: Periodontally
      accelerated osteogenic orthodontics, leukocyte and platelet-rich fibrin,
      corticotomy, osteogenesis, grafts.

PMID- 27034750
TI  - Evaluation of three different rotary systems during endodontic retreatment -
      Analysis by scanning electron microscopy.
AB  - BACKGROUND: Endodontic therapy is considered a series of important and
      interdependent steps, and failure of any of these steps may compromise the
      treatment outcome. This study aimed to evaluate the effectiveness of three
      different rotary systems in removing obturation materials during endodontic
      retreatment using scanning electron microscopy (SEM) analysis. MATERIAL AND
      METHODS: Thirty-six endodontically treated teeth were selected and divided into 3
      groups of 10 and 1 control group with 6 dental elements. The groups were divided
      according to the rotary system used for removing gutta-percha, as follows: G1:
      ProTaper system; G2: K3 system; G3: Mtwo system; and G4: Control group.
      Thereafter, the roots were split and the sections were observed under SEM, for
      analysis and counting of clear dentinal tubules, creating the variable "degree of
      dentinal tubule patency" (0: intensely clear; 1: moderately clear; 2: slightly
      clear; 3: completely blocked). The data were subjected to the Friedman and
      Kruskal-Wallis statistical tests. RESULTS: No differences were observed in the
      "degree of dentinal tubule patency" neither between the root thirds (to each
      evaluated group) nor between the groups (to each evaluated third). Nevertheless,
      when the three root thirds were grouped (providing evaluation of all root
      extension), the "degree of dentinal tubule patency" was lower in G1 than in G3
      (p<0.05), but showed no differences neither between G1 and G2 nor G2 and G3.
      CONCLUSIONS: No technique was able to completely remove the canal obturation
      material, despite G1 having shown better results, although without significant
      difference to G2 KEY WORDS:Scanning electron microscopy, NiTi, retreatment.

PMID- 27034751
TI  - Prognostic value of matrix metalloproteinase-9 expression in oral squamous cell
      carcinoma and its association with angiogenesis.
AB  - BACKGROUND: Breakdown of extracellular matrix (ECM) is one of the important
      hallmarks of cancer progression which facilitates the invasion of tumoral cells
      to the surrounding tissue. Matrix metalloproteinases (MMPs) can degrade various
      components of the ECM and basement membrane. The aim of this study was to
      determine the role of matrix metalloproteinases-9 protein in the biologic
      behavior of oral squamous cell carcinoma (OSCC) and its relation with tumor
      angiogenesis. MATERIAL AND METHODS: In this study 42 OSCC and 15 normal
      epithelium were reviewed by immunohistochemical staining for matrix
      metalloproteinases-9 and CD105. RESULTS: Matrix metalloproteinases-9 expression
      was detected in 32 OSCC specimens (76.1%), with 28 specimens (66.6%) showing
      moderate or strong expression. We observed that the expression level of matrix
      metalloproteinases-9 was positively correlated with the status of lymph node
      metastasis (N0vs. N1) (P =0.00), and clinical stage (I-II vs. III-IV) in OSCC
      patients. Microvessel density in intratumoral tissue has an association with
      lymph node metastasis and advanced clinical stage (P=0.003 and p=0.01,
      respectively). We observed that tumors with matrix metalloproteinases-9
      overexpression had a higher microvessel density counts compared with tumors with
      absent or focal immunostaining(16.2+/-5.6 vs 10.3+/-3.5 respectively, P =0.03).
      CONCLUSIONS: In conclusion present results demonstrate the marked expression of
      matrix metalloproteinases-9 and CD105 in OSCC and suggest that the expression of
      these markers is associated with tumor progression and could offer additional
      information about the aggressiveness of OSCC. In addition a significant
      relationship was noted between microvessel density count and expression of matrix
      metalloproteinases-9 which suggest that MMP9 expression may be closely related to
      tumor angiogenesis. KEY WORDS: Matrix metalloproteinases-9, CD105, squamous cell
      carcinoma, immunohistochemistry.

PMID- 27034752
TI  - Comparison of working length control consistency between hand K-files and Mtwo
      NiTi rotary system.
AB  - BACKGROUND: The purpose of this study was to investigate the consistency of
      working length control between hand instrumentation in comparison to engine
      driven Mtwo nickel-titanium rotary files. MATERIAL AND METHODS: Forty extracted
      maxillary molars were selected and divided onto two parallel groups. The working
      lengths of the mesiobuccal root canals were estimated. The teeth were fixed in a
      phantom head. The root canal preparation was carried out group 1 (n=20) with hand
      K-files, (VDW, Munich, Germany) and group 2 (n=20) with Mtwo instruments (VDW,
      Munich, Germany). Vestibulo-oral and mesio-distal directional x-ray images were
      taken before the preparation with #10 K-file, inserted into the mesiobuccal root
      canal to the working length, and after preparation with #25, #30 and #40 files.
      Working lenght changes were detected with measurements between the radiological
      apex and the instrument tips. RESULTS: In the Mtwo group a difference in the
      working competency (p<0.05) could be noticed only in the vestibulo-oral direction
      from #10 to #40 file. The hand instrument group showed a significant difference
      in working length competency for each larger file size (p<0.05) (ANOVA).
      Regression analysis in the hand instrumentation group indicated a working length
      decrease with a mean of 0,2 mm after each consecutive file size (p<0.01).
      CONCLUSIONS: The outcome of our trial indicated a high consistency in working
      length control for root canal preparation under simulated clinical condition
      using Mtwo rotary files. Mtwo NiTi rotary file did therefore proved to be more
      accurate in comparison to the conventional hand instrumentation. KEY WORDS:
      Working length, Mtwo, nickel-titanium, hand preparation, engine driven
      preparation.

PMID- 27034753
TI  - In vitro comparative study on the friction of stainless steel wires with and
      without Orthospeed(r) (JAL 90458) on an inclined plane.
AB  - BACKGROUND: During the treatment of orthodontics, in the mechanics of slide,
      there takes place friction, which they reduce the slide of the arch across
      bracket. Therefore, clinical there takes place an increase of the time of
      treatment. There are different the technologies that try to reduce this friction,
      as the self-ligating braces. The purpose of this study was to research the in
      vitro behavior of JAL 90458 as a buffering agent which reduces friction between
      brackets and stainless steel arch wires of different cross sections and sizes.
      MATERIAL AND METHODS: Three types of stainless steel wires with different cross
      sections and three types of ligatures were used with and without JAL 90458 to
      measure the friction according to the time and distance traveled by the brackets
      on an inclined plane with two angulations. The Kruskal-Wallis one-way analysis of
      variance by ranks was applied to determine the degree of friction between the
      group using and the group not using the product (P <= .05). RESULTS: Separate
      analysis of the arch wires, ligatures and angulation with and without the
      compound revealed statistically significant differences between the groups,
      showing that friction was reduced significantly when JAL 90458 was used (P <=
      .01). The 0.021x0.025" arch wires and the arch wires attached using elastic
      ligatures produce the least resistance to sliding among all of those analyzed
      when the product was not used (P <= .05). CONCLUSIONS: The results show that JAL
      90458 reduces friction independently of arch wire cross section, type of ligature
      and angulation of the measuring instrument. KEY WORDS: Friction, JAL 90458, arch
      wires, ligatures, in vitro.

PMID- 27034754
TI  - Effect of glycine pretreatment on the shear bond strength of a CAD/CAM resin nano
      ceramic material to dentin.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of glycine
      pretreatment on the shear bond strength between dentin and a CAD/CAM resin nano
      ceramic material (LavaTM Ultimate Restorative), bonded together with adhesive
      cements using three different luting protocols (total-etch; self-etch; self
      adhesive). MATERIAL AND METHODS: Thirty cylinders were milled from resin nano
      ceramic blocks with CAD/CAM technology. The cylinders were subsequently cemented
      to the exposed dentin of 30 bovine permanent mandibular incisors. The specimens
      were assigned into six groups of five teeth each according to luting procedure
      and dentin pretreatment. In the first two groups (A1, A2) 10 cylinders were
      cemented using a total-etch protocol; in groups B1 and B2, 10 cylinders were
      cemented using a self-etch protocol; in groups C1 and C2, 10 cylinders were
      cemented using a self-adhesive protocol; in groups A1, B1 and C1 the dentinal
      surface was also treated with glycine powder. All cemented specimens were
      submitted to a shear bond strength test. Statistical analysis was performed with
      Stata 9.0 software. RESULTS: ANOVA showed the presence of significant differences
      among the various groups (P <0.0001). CONCLUSIONS: Glycine did not change the
      different bond strength demonstrated by the various luting protocols tested.
      Conventional resin composite cements used together with a self-etch adhesive
      reported the highest values. However the use of glycine seems to increase the
      bond strength of self-adhesive resin cements. KEY WORDS: Adhesive cements,
      CAD/CAM, glycine, luting system, resin nano ceramic, shear bond strength.

PMID- 27034755
TI  - Continuous neurophatic orofacial pain: A retrospective study of 23 cases.
AB  - BACKGROUND: To determine the clinical characteristics of Continuous Neuropathic
      Orofacial Pain in patients that suffer Persistent Idiopathic Facial Pain (PIFP),
      Painful Post-Traumatic Trigeminal Neuropathy (PPTTN) or Burning Mouth Syndrome
      (BMS) and to describe their treatment. MATERIAL AND METHODS: A retrospective
      observational study was made, reviewing the clinical history of the patients
      diagnosed with Continuous Neuropathic Orofacial Pain between 2004 and 2011 at the
      Orofacial Pain Unit of the Master of Oral Surgery and Implantology of the
      University of Barcelona and at the Orofacial Pain Unit of the Teknon Medical
      Center of Barcelona. RESULTS: The average age of the patients with Continuous
      Neuropathic Orofacial Pain was 54.5, with a clear female predominance (86.9%,
      n=20). Of all patients, 60.9% (n=14) were suffering a PIFP, 21.7% (n=5) had a BMS
      and 17.4% (n=4) were presenting a PPTTN. The pain quality described by the
      patients with Continuous Neuropathic Orofacial Pain was oppressive (43.47%,
      n=10), widely represented by patients with PIFP, and burning (39.13%, n=9) being
      the only quality that described patients with BMS. The treatment carried out with
      the patients was only pharmacologic. The most used drugs for the treatment of
      PIFP and PPTTN were clonazepam (50%, n=9) and amitriptyline (44.44%, n=8).
      However, a 55.5% (n=10) of the patients with PIFP or PPTTN required the
      association of two or more drugs for a correct pain control. All the patients
      with BMS responded satisfactorily to clonazepam. CONCLUSIONS: Continuous
      Neuropathic Orofacial Pain is a little known condition among the general
      population, physicians and dentists. This favors a late diagnosis and inaccurate
      treatments which entail unnecessary suffering. It is important to inform both the
      general population and health professionals concerning this painful condition.
      KEY WORDS: Continuous neuropathic orofacial pain, persistent idiopathic facial
      pain, painful post-traumatic trigeminal neuropathy, burning mouth syndrome,
      atypical odontalgia.

PMID- 27034756
TI  - Effectiveness of intra-alveolar chlorhexidine gel in reducing dry socket
      following surgical extraction of lower third molars. A pilot study.
AB  - BACKGROUND: Dry socket is one of the most studied complications in dentistry and
      several studies have sought an effective and safe method for its prevention and
      treatment. The aim of this study was to evaluate the effectiveness of intra
      alveolar gel chlorhexidine in preventing dry socket after the surgical removal of
      third molars. MATERIAL AND METHODS: The sample involved the treatment of 40
      patients who required extraction of third molars impacted, which were randomly
      assigned to research groups: experimental group (chlorhexidine gel 0.12%) and
      control group (placebo gel). Performed the extraction was administered 1 mL of
      chlorhexidine gel or 1 mL of placebo gel within the socket. The removal of suture
      was on the fifth postoperative day in which the presence or absence of dry socket
      was evaluated. RESULTS: No relationship between the appearance of dry socket
      after application of chlorhexidine gel or placebo gel (X2 test, p = 0.311) was
      found. However, significant differences (U Mann-Whitney test, p = 0.036) in the
      pain presented on the fifth postoperative day were evident (VAS). CONCLUSIONS:
      The administration of intra-alveolar chlorhexidine gel 0.12% could generate a
      better response to postoperative pain after the removal of third molars. KEY
      WORDS: Third molar surgery, dry socket, chorhexidine gel.

PMID- 27034757
TI  - Clinical evaluation of neodymium-iron-boron (Ne2Fe14B) rare earth magnets in the
      treatment of mid line diastemas.
AB  - BACKGROUND: To evaluate the closure of midline diastema using the Neodymium-Iron
      Boron magnets and to compare the treatment duration of midline diastemas with the
      use of magnets compared to regular orthodontic treatment. MATERIAL AND METHODS:
      Thirty patients with age group 12 to 30 years with the midline diastema ranging
      from 0.5 to 3mm were selected. These patients were divided into two groups.
      Diastema closure in one group was accomplished by conventional method, in other
      group was done with Ne2Fe14B magnets. These magnets were fitted to the labial
      surfaces of the maxillary central incisors such a way that the opposite poles of
      the magnets face each other. At each appointment, study models and radiographs
      were taken for study subjects and the midline diastema was measured using digital
      vernier calipers on the study models obtained. Descriptive statistics carried out
      using Paired t-test. RESULTS: Subjects treated with Ne2Fe14B magnets showed a
      significant difference compared to fixed orthodontic appliance subjects with
      respect to time of closure, rate of space closure and incisal inclination.
      Significant difference between 2 groups with reduction of 64.6 days in time to
      diastema closure in subjects treated with Ne2Fe14B magnets (P<0.05). CONCLUSIONS:
      Ne2Fe14B magnets more efficient in complete closure of mid line diastema in less
      duration of time. KEY WORDS: Midline diastema, Ne2Fe14B magnets, rare earth
      magnets, space closure.

PMID- 27034758
TI  - Various forms of tobacco usage and its associated oral mucosal lesions.
AB  - BACKGROUND: To study the various forms of tobacco usage and its associated oral
      mucosal lesions among the patients attending Vishnu Dental College Bhimavaram.
      MATERIAL AND METHODS: An observational cross-sectional study was conducted in a
      total of 450 patients who were divided into three groups based upon type of
      tobacco use, as Group-1 Reverse smoking, Group-2 Conventional smoking, Group-3
      Smokeless tobacco group and each group consists of 150 subjects. RESULTS: Reverse
      smoking was observed to be more prevalent among old females with smoker's palate
      and carcinomatous lesions being the most common. Conventional smoking was
      observed more in male patients with maximum occurrence of leukoplakia and tobacco
      associated melanosis. Smokeless tobacco habit was predominantly seen in younger
      males. Habit specific lesions like tobacco pouch keratosis, Oral Submucous
      Fibrosis (OSMF), Quid induced lichenoid reaction were noticed in smokeless
      tobacco habit group except for erythroplakia which was noticed only in
      conventional smoking group and it was not significant statistically. CONCLUSIONS:
      In the present study it was found that the usage of reverse smoking habit was
      most commonly seen in females and this habit is practiced in and surrounding
      areas of Bhimavaram with more occurrence of carcinoma compared to conventional
      smoking and smokeless tobacco. KEY WORDS: Tobacco, reverse smoking, conventional
      smoking, smokeless tobacco, carcinoma.

PMID- 27034759
TI  - Marginal integrity of low-shrinkage and methacrylate-based composite resins:
      Effect of three different hemostatic agents.
AB  - BACKGROUND: Moisture control is very important in restorative procedures in
      dentistry. Use of hemostatic agents helps control moisture; however, they might
      result in changes on enamel and dentin surfaces, affecting composite resin bond
      quality. The aim of this in vitro study was to evaluate the marginal microleakage
      of two different composite resins with the use of three different hemostatic
      agents. MATERIAL AND METHODS: Standardized Class V cavities were prepared on the
      buccal and lingual surfaces of 48 premolars with cervical margins 1 mm apical to
      the cementoenamel junction (CEJ). The samples were randomly divided into 8
      groups. In groups 1 to 4, an etch-and-rinse adhesive (Adper Single Bond) was
      applied as the bonding system, followed by exposure to different hemostatic
      agent: group 1: no hemostatic agent (control); group 2: ViscoStat; group 3:
      ViscoStat Clear; and group 4: trichloracetic acid, as hemostatic agents. The
      cavities were restored with Z-250 composite resin. In group 5 to 8 Silorane
      System Adhesive (Filtek P90 Adhesive) was applied as a bonding agent, followed by
      exposure to different hemostatic agents in a manner similar to that in groups 1to
      4. The cavities were restored with Filtek P90, a low-shrinkage composite resin.
      The samples in each group were evaluated for dye penetration under a
      stereomicroscope at *36 after 24 hours and a 500-round thermocycling procedure at
      enamel and dentin margins. Statistical analysis was carried out using Kruskal
      Wallis and Mann-Whitney tests (alpha=0.05). RESULTS: Z-250 composite resin
      exhibited significantly higher dentin microleakage scores compared to Filtek P90
      (P = 0.004). Trichloracetic acid increased dentin microleakage with Filtek P90
      (P=0.033). CONCLUSIONS: Under the limitations of this in vitro study, application
      of hemostatic agents did not affect microleakage of the two tested composite
      resins except for trichloracetic acid that increased marginal microleakage when
      used with Filtek P90. KEY WORDS: Composite resin, dental leakage, hemostatics,
      silorane system adhesive.

PMID- 27034760
TI  - The role of serum biomarkers in the diagnosis and prognosis of oral cancer: A
      systematic review.
AB  - INTRODUCTION: Oral cancer is one of the causes of major morbidity and mortality
      in the world although incidence varies in the different geographical locations
      and races. Advances in molecular biology and cancer research have allowed
      elucidating serum biomarkers to improve diagnostic methods. The aim of this
      article systematic review is to highlight the utility and clinical value of serum
      biomarkers in the diagnosis and prognosis of oral cancer. MATERIAL AND METHODS: A
      systematic literature review using PubMed (MEDLINE databases) revealed a total of
      140 articles related to this topic. Of those articles, 29 were included in the
      final review. We included articles published in English in the last five years,
      developed in human as cases and controls studies, retrospective or prospective
      studies and specific studies that analyzed a certain biomarker in serum. RESULTS:
      All of the studies include in this systematic review found significant
      differences in patients. Of those articles included, 2 used biomarkers to
      determinate cancerous phenotype, 11 mentioned their results were associated with
      worse prognosis and overall survival, 4 correlated biomarker concentration to
      clinical stages, 4 concluded it could be a helpful in diagnosis and 8 studies did
      not find a clear utility of the analysed biomarker. Due to differences in the
      presentation of data, meta-analysis was not possible. CONCLUSIONS: Biomarker use
      for diagnosis and prognosis is supported by clinical and scientific evidence is
      relevant. Nevertheless, after selecting a certain biomarker, monitoring protocols
      should be established in oral and maxillofacial surgeons teams so as we have a
      correct understanding of biological values. KEY WORDS: Serum biomarkers, oral
      cancer, diagnosis, prognosis.

PMID- 27034761
TI  - The effect of radiotherapy on survival of dental implants in head and neck cancer
      patients.
AB  - OBJECTIVES: To explore the current literature of the survival of dental implants
      in irradiated head and neck cancer patients considering the role of implant
      location, bone augmentation, dose of radiation and timing of implant placement.
      STUDY DESIGN: Pubmed search was conducted to identify articles published between
      January 2000 and December 2014 and presenting data of dental implant survival
      with radiotherapy in head and neck cancer patients. Studies on animal subjects
      and craniofacial implants were excluded. RESULTS: 18 articles out of 27 were
      eligible for inclusion in this systematic review. 12 out of 18 studies reported
      favorable outcome of dental implants and radiotherapy with survival rates between
      74.4% and 97%. Seven out of ten studies comparing the survival rates according to
      site of implant placement reported that implants were found to osseointegrate
      with greater success in the irradiated mandible than irradiated maxilla. 5
      studies which compared implant survival in irradiated native bone versus
      irradiated grafted bone reported that irradiated grafted bone showed a
      significantly reduced dental implant survival rate in comparison to irradiated
      native bone. 6 out of 18studies in which radiation doses exceeded 70 Gy reported
      lower survival rates of dental implants in comparison to the studies in which
      radiation doses were <=70Gy. Higher survival rates were reported in 2 studies in
      which implants placement was before radiotherapy in comparison to the remaining
      16 studies in which implants placement was after radiotherapy. CONCLUSIONS:
      Dental implants may be affected by radiotherapy especially when they are placed
      in maxilla, in grafted bone, or after radiation, however, they remain a
      functional option for rehabilitation of head and cancer patients. More
      Prospective cohort studies and randomized controlled trails are still needed to
      draw more evidence based conclusions. KEY WORDS: Dental implants, implant
      survival, radiotherapy, head and neck cancer.

PMID- 27034762
TI  - Treatment of oral mucositis due to chemotherapy.
AB  - INTRODUCTION: The management of oral mucositis is a challenge, due to its complex
      biological nature. Over the last 10 years, different strategies have been
      developed for the management of oral mucositis caused by chemotherapy in cancer
      patients. MATERIAL AND METHODS: An exhaustive search was made of the PubMed
      Medline, Cochrane Library and Scopus databases, crossing the key words "oral
      mucositis", "prevention" and "treatment" with the terms "chemotherapy" and
      "radiotherapy" by means of the boolean operators "AND" and "NOT". A total of 268
      articles were obtained, of which 96 met the inclusion criteria. RESULTS: Several
      interventions for the prevention of oral mucositis, such as oral hygiene
      protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan,
      among others, were found to yield only limited benefits. Other studies have
      reported a decrease in the appearance and severity of mucositis with the use of
      cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors,
      topical polyvinylpyrrolidone, and low power laser irradiation. CONCLUSIONS: Very
      few interventions of confirmed efficacy are available for the management of oral
      mucositis due to chemotherapy. However, according to the reviewed literature, the
      use of palifermin, cryotherapy and low power laser offers benefits, reducing the
      incidence and severity of oral mucositis - though further studies are needed to
      confirm the results obtained. KEY WORDS: Chemotherapy-Induced Oral Mucositis
      Treatment.

PMID- 27034763
TI  - Myositis ossificans of the masseter muscle: A rare location. Report of a case and
      review of literature.
AB  - BACKGROUND: Myositis Ossificans is a rare heterotopic bone formation within a
      muscle being the masticatory muscles exceptionally involved. In most cases there
      is a previous trauma, bearing in mind that there may be many other etiologies. CT
      scan and panoramic radiographs along with histological findings are essential
      diagnostic aids. CASE DESCIPTION: We report a rare case of MO of masseter muscle
      in 49 years-old woman after repetitive wisdom tooth infection with the discussion
      of clinical, radiological and histological features. CLINICAL IMPLICATIONS: MO is
      a rare disease of masticatory muscles being the masseter the most frequently
      affected. Wide surgical excision with free margins is the treatment of choice
      although close postoperative monitoring it's essential to avoid relapses. KEY
      WORDS: Myositis ossificans, myositis ossificans traumatica, masticatory muscles,
      masseter muscle, trauma.

PMID- 27034764
TI  - "Osteolipoma of buccal mucosa: Case report and literature review".
AB  - Osteolipoma affecting oral cavity is indeed rare. We hereby report a case of
      osteolipoma affecting buccal mucosa. A review of literature of osteolipoma of
      oral cavity, particularly on radiographic/imaging findings was done. Only 16
      cases of Osteolipoma of oral cavity are reported in the literature. The
      radiographic findings of our case, i.e. multiple dense homogenous radio-opaque
      structures was reported earlier only in one case [out of 16] of osteolipoma of
      oral cavity. KEY WORDS: Lipoma, osteolipoma, panoramic radiography, radio-opaque,
      radiography.

PMID- 27034766
TI  - The central odontogenic fibroma: How difficult can be making a preliminary
      diagnosis.
AB  - Central odontogenic fibroma (COF) is a rare benign odontogenic tumor derived from
      the dental ectomesenchymal tissues. A 16-year-old Caucasian female patient was
      referred by her dentist for a radiolucent asymptomatic area associated with the
      crown of the impacted lower right third molar. A preliminary diagnosis of a
      follicular cyst was supposed. The lesion was surgically removed under general
      anesthesia together with the impacted tooth. The microscopic diagnosis of the
      excised tissue revealed an odontogenic fibroma. No clinical or radiographic signs
      of recurrence were found five years after surgical excision. Despite the various
      differential diagnoses of homogeneous unilocular and well delimited
      radiolucencies of the jaws, enucleation with peripheral curettage, without any
      other pre-operative imaging exams or biopsies, can be considered as the treatment
      of choice. KEY WORDS: Differential diagnosis, impacted third molar, radiographic
      imaging, microscopic diagnosis, odontogenic fibroma.

PMID- 27034765
TI  - Solitary central osteoma of mandible in a geriatric patient: Report and review.
AB  - Solitary central osteomas of jaw are extremely rare lesions with only few
      previously documented cases. This paper reports a case of large solitary central
      osteoma involving mandible symphysis- parasymphysis region in an elderly female
      patient. A brief review of similar cases reported in the literature is also
      provided in this paper. KEY WORDS: Osteomas, osteogenic,bone, tumor, jaw,
      mandible.

PMID- 27034767
TI  - Posttraumatic carotid-cavernous fistula: Pathogenetic mechanisms, diagnostic
      management and proper treatment. A case report.
AB  - Carotid-cavernous fistulas are an uncommon diseases characterized by abnormal
      communications between arteries and veins located in the cavernous sinus.
      According with Barrow's classification they could be divided in two groups:
      direct and indirect. The typical symptoms showed by theses pathologies are:
      pulsating exophthalmos and orbital blow. The present study describes a case of
      direct posttraumatic carotid-cavernous fistula in a 26 years old man.
      Furthermore, we present the images that we used to make the diagnosis. In this
      light, we decided to treat this case with endovascular approach after considering
      several therapeutic options. The aim of the present report is twofold. First, we
      examine the importance of the proper management of the direct posttraumatic
      carotid-cavernous fistula. Second, we describe this rare syndrome with the goal
      of proposing suitable treatments. KEY WORDS: Carotid cavernous fistulas,
      pulsating exophthalmos, orbital blow, endovascular approach, Barrow's
      classification.

PMID- 27034768
TI  - Sex differences in the association between infant markers and later autistic
      traits.
AB  - BACKGROUND: Although it is well established that the prevalence of autism
      spectrum disorder (ASD) is higher in males than females, there is relatively
      little understanding of the underlying mechanisms and their developmental time
      course. Sex-specific protective or risk factors have often been invoked to
      explain these differences, but such factors are yet to be identified. METHODS: We
      take a developmental approach, using a prospective sample of 104 infants at high
      and low familial risk for ASD, to characterise sex differences in infant markers
      known to predict emerging autism symptoms. We examine three markers previously
      shown to be associated with later autistic social-communication symptoms: the
      Autism Observation Scale for Infants (AOSI) total score, attention disengagement
      speed and gaze following behaviour. Our aim was to test whether sex differences
      were already present in these markers at 1 year of age, which would suggest sex
      specific mechanisms of risk or protection. RESULTS: While no sex differences were
      found in any of the three markers investigated, we found sex differences in their
      relationship to 3-year autism traits; all three markers significantly predicted
      later autism traits only in the boys. CONCLUSIONS: Previously identified 'early
      autism markers' were associated with later autism symptoms only in boys. This
      suggests that there may be additional moderating risk or protective factors which
      remain to be identified. Our findings have important implications for prospective
      studies in terms of directly testing for the moderating effect of sex on emerging
      autistic traits.

PMID- 27034769
TI  - Representing vision and blindness.
AB  - BACKGROUND: There have been relatively few attempts to represent vision or
      blindness ontologically. This is unsurprising as the related phenomena of sight
      and blindness are difficult to represent ontologically for a variety of reasons.
      Blindness has escaped ontological capture at least in part because: blindness or
      the employment of the term 'blindness' seems to vary from context to context,
      blindness can present in a myriad of types and degrees, and there is no precedent
      for representing complex phenomena such as blindness. METHODS: We explore current
      attempts to represent vision or blindness, and show how these attempts fail at
      representing subtypes of blindness (viz., color blindness, flash blindness, and
      inattentional blindness). We examine the results found through a review of
      current attempts and identify where they have failed. RESULTS: By analyzing our
      test cases of different types of blindness along with the strengths and
      weaknesses of previous attempts, we have identified the general features of
      blindness and vision. We propose an ontological solution to represent vision and
      blindness, which capitalizes on resources afforded to one who utilizes the Basic
      Formal Ontology as an upper-level ontology. CONCLUSIONS: The solution we propose
      here involves specifying the trigger conditions of a disposition as well as the
      processes that realize that disposition. Once these are specified we can
      characterize vision as a function that is realized by certain (in this case)
      biological processes under a range of triggering conditions. When the range of
      conditions under which the processes can be realized are reduced beyond a certain
      threshold, we are able to say that blindness is present. We characterize vision
      as a function that is realized as a seeing process and blindness as a reduction
      in the conditions under which the sight function is realized. This solution is
      desirable because it leverages current features of a major upper-level ontology,
      accurately captures the phenomenon of blindness, and can be implemented in many
      domain-specific ontologies.

PMID- 27034771
TI  - Cardiovascular risk with DPP-4 inhibitors: latest evidence and clinical
      implications.

PMID- 27034770
TI  - HOX gene complement and expression in the planarian Schmidtea mediterranea.
AB  - BACKGROUND: Freshwater planarians are well known for their regenerative
      abilities. Less well known is how planarians maintain spatial patterning in long
      lived adult animals or how they re-pattern tissues during regeneration. HOX genes
      are good candidates to regulate planarian spatial patterning, yet the full
      complement or genomic clustering of planarian HOX genes has not yet been
      described, primarily because only a few have been detectable by in situ
      hybridization, and none have given morphological phenotypes when knocked down by
      RNAi. RESULTS: Because the planarian Schmidtea mediterranea (S. mediterranea) is
      unsegmented, appendage less, and morphologically simple, it has been proposed
      that it may have a simplified HOX gene complement. Here, we argue against this
      hypothesis and show that S. mediterranea has a total of 13 HOX genes, which
      represent homologs to all major axial categories, and can be detected by whole
      mount in situ hybridization using a highly sensitive method. In addition, we show
      that planarian HOX genes do not cluster in the genome, yet 5/13 have retained
      aspects of axially restricted expression. Finally, we confirm HOX gene axial
      expression by RNA deep-sequencing 6 anterior-posterior "zones" of the animal,
      which we provide as a dataset to the community to discover other axially
      restricted transcripts. CONCLUSIONS: Freshwater planarians have an unappreciated
      HOX gene complexity, with all major axial categories represented. However, we
      conclude based on adult expression patterns that planarians have a derived body
      plan and their asexual lifestyle may have allowed for large changes in HOX
      expression from the last common ancestor between arthropods, flatworms, and
      vertebrates. Using our in situ method and axial zone RNAseq data, it should be
      possible to further understand the pathways that pattern the anterior-posterior
      axis of adult planarians.

PMID- 27034772
TI  - Drug-induced falls in older persons: is there a role for therapeutic drug
      monitoring?
AB  - BACKGROUND: Falls are the leading cause of injuries among older persons. Because
      of ageing societies worldwide, falls are expected to become a prominent public
      health problem. The usage of several types of drugs has been associated with an
      increased fall and fracture risk. In order to reduce future falls, preventative
      measures are needed. Therapeutic drug monitoring may help to identify persons who
      are at risk for falls due to drug use. The aim was to demonstrate how drugs can
      contribute to falls and the role of therapeutic drug monitoring. METHODS: We
      present a descriptive case series of four patients. RESULTS: All patients were
      referred to the geriatric outpatient clinic of a university medical center. The
      presented cases contained different underlying mechanisms contributing to an
      increased fall risk in older adults, including renal failure, genetic variation,
      overdose and ageing. CONCLUSION/DISCUSSION: Older adults are more prone to the
      side effects of drug use, including falls. Therapeutic drug monitoring may be
      useful to identify the patients who have an increased drug-related fall risk and
      to prevent future falls by individualizing the drug regime.

PMID- 27034773
TI  - Use of doripenem and risk of seizure and renal impairment in US hospitalized
      patients: a retrospective cohort study.
AB  - OBJECTIVES: A large retrospective database study was conducted to assess the
      incidence rate of treatment-emergent renal impairment/failure, seizure, and
      hemolytic anemia in doripenem and imipenem intravenous (IV)-exposed patients
      treated for complicated urinary tract infection (cUTI) and complicated intra
      abdominal infection (cIAI) in US hospitals. METHODS: Using the Premier
      PerspectiveTM Database (PPD), which maintains hospital discharge records for over
      309 million patients, the incidence rate of treatment-emergent renal
      impairment/failure, seizure, and hemolytic anemia in the doripenem-treated
      compared with imipenem IV-treated population was examined. RESULTS: The
      unadjusted doripenem rate ratio (RR) for renal impairment/failure relative to
      imipenem IV was 1.13 [95% confidence interval (CI) 1.07-1.21; p < 0.0001]. The
      unadjusted doripenem rate ratio for seizure relative to imipenem IV was 0.74 (95%
      CI 0.52-1.05; p = 0.07). In the comparative safety analysis, adjusted incidence
      rates of renal impairment/failure between doripenem-exposed patients and a
      propensity score-matched comparator cohort of imipenem IV-exposed patients showed
      no statistically significant difference in cUTI [RR = 1.02; 95% CI 0.93-1.12; p =
      0.71] or cIAI (RR = 1.17; 95% CI 1.00-1.36; p = 0.05). Likewise, there was no
      statistically significant difference in adjusted incidence rates for seizures in
      doripenem-treated versus matched imipenem-treated patients for cUTI (RR = 0.69;
      95% CI 0.41-1.14; p = 0.15) or cIAI (RR = 0.45; 95% CI 0.15-1.41; p = 0.17). No
      hemolytic anemia events were observed in this study. CONCLUSIONS: In this large
      retrospective cohort study of US hospitalized patients, no statistically
      significant differences in the adjusted relative rates of renal
      impairment/failure and seizure were observed between doripenem and a propensity
      score-matched comparator cohort of imipenem IV patients in the treatment of cUTI
      and cIAI.

PMID- 27034775
TI  - Methylation status of DJ-1 in leukocyte DNA of Parkinson's disease patients.
AB  - BACKGROUND: DJ-1 has been thought as a candidate biomarker for Parkinson's
      disease (PD). It was found reduced in PD brains, CSF and saliva, although there
      were conflicting results. How DJ-1 expression may be regulated is not clear.
      Recently, blood-based DNA methylation represents a highly promising biomarker for
      PD by regulating the causative gene expression. Thus, in this study, we try to
      explore whether blood-based DNA methylation of DJ-1 could be used as a biomarker
      to differentiate PD patients from normal control (NC), and whether DNA
      methylation could regulate DJ-1 expression in a SH-SY5Y cell model. METHODS:
      Forty PD patients and 40 NC were recruited in this study. DNA was extracted from
      peripheral blood leukocytes (PBLs). Methylation status of two CpG islands (CpG1
      and CpG2) in promoter region of DJ-1 was explored by bisulfite specific PCR-based
      sequencing method. Methylation inhibitor 5-Aza-dC was used to treat SH-SY5Y cell
      line, DJ-1 level was detected in both mRNA and protein level. RESULTS: CpG sites
      in these two CpG islands (CpG1 and CpG2) of DJ-1 were unmethylated in both PD and
      NC group. In SH-SY5Y cell model treated by methylation inhibitor, there was no
      significant change of DJ-1 expression in either mRNA level or protein level.
      CONCLUSIONS: Our results indicated that DNA methylation inhibitor didn't alter DJ
      1 gene expression in SH-SY5Y cell model, and DNA methylation of DJ-1 promoter
      region in PBLs level might not be an efficient biomarker for PD patients.

PMID- 27034776
TI  - The implications of whole-genome sequencing in the control of tuberculosis.
AB  - The availability of whole-genome sequencing (WGS) as a tool for the diagnosis and
      clinical management of tuberculosis (TB) offers considerable promise in the fight
      against this stubborn epidemic. However, like other new technologies, the best
      application of WGS remains to be determined, for both conceptual and technical
      reasons. In this review, we consider the potential value of WGS in the clinical
      laboratory for the detection of Mycobacterium tuberculosis and the prediction of
      antibiotic resistance. We also discuss issues pertaining to data generation,
      interpretation and dissemination, given that WGS has to date been generally
      performed in research labs where results are not necessarily packaged in a
      clinician-friendly format. Although WGS is far more accessible now than it was in
      the past, the transition from a research tool to study TB into a clinical test to
      manage this disease may require further fine-tuning. Improvements will likely
      come through iterative efforts that involve both the laboratories ready to move
      TB into the genomic era and the front-line clinical/public health staff who will
      be interpreting the results to inform management decisions. 

PMID- 27034774
TI  - Strategies and methods to study female-specific cardiovascular health and
      disease: a guide for clinical scientists.
AB  - BACKGROUND: In 2001, the Institute of Medicine's (IOM) report, "Exploring the
      Biological Contributions to Human Health: Does Sex Matter?" advocated for better
      understanding of the differences in human diseases between the sexes, with
      translation of these differences into clinical practice. Sex differences are well
      documented in the prevalence of cardiovascular (CV) risk factors, the clinical
      manifestation and incidence of cardiovascular disease (CVD), and the impact of
      risk factors on outcomes. There are also physiologic and psychosocial factors
      unique to women that may affect CVD risk, such as issues related to reproduction.
      METHODS: The Society for Women's Health Research (SWHR) CV Network compiled an
      inventory of sex-specific strategies and methods for the study of women and CV
      health and disease across the lifespan. References for methods and strategy
      details are provided to gather and evaluate this information. Some items comprise
      robust measures; others are in development. RESULTS: To address female-specific
      CV health and disease in population, physiology, and clinical trial research,
      data should be collected on reproductive history, psychosocial variables, and
      other factors that disproportionately affect CVD in women. Variables related to
      reproductive health include the following: age of menarche, menstrual cycle
      regularity, hormone levels, oral contraceptive use, pregnancy
      history/complications, polycystic ovary syndrome (PCOS) components, menopause
      age, and use and type of menopausal hormone therapy. Other factors that
      differentially affect women's CV risk include diabetes mellitus, autoimmune
      inflammatory disease, and autonomic vasomotor control. Sex differences in aging
      as well as psychosocial variables such as depression and stress should also be
      considered. Women are frequently not included/enrolled in mixed-sex CVD studies;
      when they are included, information on these variables is generally not
      collected. These omissions limit the ability to determine the role of sex
      specific contributors to CV health and disease. Lack of sex-specific knowledge
      contributes to the CVD health disparities that women face. CONCLUSIONS: The
      purpose of this review is to encourage investigators to consider ways to increase
      the usefulness of physiological and psychosocial data obtained from clinical
      populations, in an effort to improve the understanding of sex differences in
      clinical CVD research and health-care delivery for women and men.

PMID- 27034778
TI  - Simulation of high-intensity focused ultrasound lesions in presence of boiling.
AB  - BACKGROUND: The lesions induced by high-intensity focused ultrasound (HIFU)
      thermal ablations are particularly difficult to simulate due to the complexity of
      the involved phenomena. In particular, boiling has a strong influence on the
      lesion shape. Thus, it must be accounted for if it happens during the pulses to
      be modeled. However, no acoustic model enables the simulation of the resulting
      wave scattering. Therefore, we propose an equivalent model for the heat
      deposition pattern in the presence of boiling. METHODS: Firstly, the acoustic
      field is simulated with k-Wave and the heat source term is calculated. Then, a
      thermal model is designed, including the equivalent model for boiling. It is
      rigorously calibrated and validated through the use of diversified ex vivo and in
      vivo data, including usually unexploited data types related to the bubble clouds.
      RESULTS: The proposed model enabled to efficiently simulate unitary pulses
      properties, including the sizes of the lesions, their morphology, the boiling
      onset time, and the influence of the boiling onset time on the lesions sizes.
      CONCLUSIONS: In this article, the whole procedure of model design, calibration,
      and validation is discussed. In addition to depicting the creative use of data,
      our modeling approach focuses on the understanding of the mechanisms influencing
      the shape of the lesion. Further work is required to study the influence of the
      remaining bubble clouds in the context of pulse groups.

PMID- 27034777
TI  - Best practice in the prevention and management of paediatric respiratory
      syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) infection is ubiquitous with almost all infants
      having been infected by 2 years of age and lifelong repeated infections common.
      It is the second largest cause of mortality, after malaria, in infants outside
      the neonatal period and causes up to 200,000 deaths per year worldwide. RSV
      results in clinical syndromes that include upper respiratory tract infections,
      otitis media, bronchiolitis (up to 80% of cases) and lower respiratory tract
      disease including pneumonia and exacerbations of asthma or viral-induced wheeze.
      For the purposes of this review we will focus on RSV bronchiolitis in infants in
      whom the greatest disease burden lies. For infants requiring hospital admission,
      the identification of the causative respiratory virus is used to direct cohorting
      or isolation and infection control procedures to minimize nosocomial
      transmission. Nosocomial RSV infections are associated with poorer clinical
      outcomes, including increased mortality, the need for mechanical ventilation and
      longer length of hospital stay. Numerous clinical guidelines for the management
      of infants with bronchiolitis have been published, although none are specific for
      RSV bronchiolitis. Ribavirin is the only licensed drug for the specific treatment
      of RSV infection but due to drug toxicity and minimal clinical benefit it has not
      been recommended for routine clinical use. There is currently no licensed vaccine
      to prevent RSV infection but passive immunoprophylaxis using a monoclonal
      antibody, palivizumab, reduces the risk of hospitalization due to RSV infection
      by 39-78% in various high-risk infants predisposed to developing severe RSV
      disease. The current management of RSV bronchiolitis is purely supportive, with
      feeding support and oxygen supplementation until the infant immune system mounts
      a response capable of controlling the disease. The development of a successful
      treatment or prophylactic agent has the potential to revolutionize the care and
      outcome for severe RSV infections in the world's most vulnerable infants. 

PMID- 27034782
TI  - Single centre outcomes from definitive chemo-radiotherapy and single modality
      radiotherapy for locally advanced oesophageal cancer.
AB  - BACKGROUND: Definitive chemo-radiotherapy (dCRT) has been advocated as an
      alternative to surgical resection for the treatment of locally advanced
      oesophageal cancer (OC). We have retrospectively reviewed 4 years' experience of
      patients (pts) who underwent contemporary staging and were treated with
      concurrent chemo-radiotherapy (dCRT) or single modality radical radiotherapy (RT)
      with curative intent. METHODS: Retrospective analysis permitted identification of
      consecutive patients who underwent contemporary staging prior to non-surgical
      treatment for locally advanced oesophageal carcinoma. The primary outcomes were
      overall survival (OS) and disease-free survival (DFS), adjusted for baseline
      differences in age, tumour staging and histological cell type. All patients were
      treated with either dCRT or single modality RT within a single centre between
      2009 and 2012. RESULTS: We identified 235 patients in total [median age 69.8
      years, male =130 pts, female =105 pts, adenocarcinoma (ACA) =85 pts, squamous
      =150 pts]. A total of 190 pts received dCRT and 45 patients were treated with RT.
      All patients were staged with CT of chest, abdomen and pelvis, 226 patients
      underwent endoscopic ultrasound (EUS), and 183 patients had PET-CT. Patients
      treated with dCRT demonstrated longer OS (27 vs. 25 months respectively, P=0.02)
      and DFS (31 vs. 16 months respectively, P=0.01) compared to those treated with
      RT. More advanced tumour stage (stage 3 vs. stage 1/2) at presentation conferred
      poorer OS (32 vs. 38.2 months, P=0.02) and DFS (11 vs. 28 months, P=0.013). We
      demonstrated an acceptable toxicity profile with only 77 patients (32.8%)
      suffering grade 3 toxicity and 9 patients (4.2%) experiencing grade 4 toxicity by
      CTC criteria. The NG/PEG feeding rates were 4% across all treated patients.
      CONCLUSIONS: This retrospective analysis is in keeping with current treatment
      paradigms emphasising the importance and safety of concurrent CRT in maximising
      curative potential for patients undergoing non-surgical treatment of OC. Although
      retrospective, in comparison to similar retrospective series from both our centre
      and historical literature, this data suggest improvements in OS and DFS, possibly
      due to improved patient selection through the use of more effective tumour
      staging.

PMID- 27034780
TI  - Evolutionary reversion of live viral vaccines: Can genetic engineering subdue it?
AB  - Attenuated, live viral vaccines have been extraordinarily successful in
      protecting against many diseases. The main drawbacks in their development and use
      have been reliance on an unpredictable method of attenuation and the potential
      for evolutionary reversion to high virulence. Methods of genetic engineering now
      provide many safer alternatives to live vaccines, so if live vaccines are to
      compete with these alternatives in the future, they must either have superior
      immunogenicity or they must be able to overcome these former disadvantages.
      Several live vaccine designs that were historically inaccessible are now feasible
      because of advances in genome synthesis. Some of those methods are addressed
      here, with an emphasis on whether they enable predictable levels of attenuation
      and whether they are stable against evolutionary reversion. These new designs
      overcome many of the former drawbacks and position live vaccines to be
      competitive with alternatives. Not only do new methods appear to retard
      evolutionary reversion enough to prevent vaccine-derived epidemics, but it may
      even be possible to permanently attenuate live vaccines that are transmissible
      but cannot evolve to higher virulence under prolonged adaptation.

PMID- 27034783
TI  - Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in
      esophagogastric adenocarcinoma.
AB  - BACKGROUND: Targeting human epidermal growth factor receptor 2 (HER2) with
      trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival.
      The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in
      early stage EGA is under investigation. This study analyzed the pattern of HER2
      overexpression in matched-pair tumor samples of patients who underwent
      neoadjuvant CRT followed by surgery. METHODS: All patients with EGA who underwent
      standard neoadjuvant CRT followed by esophagectomy at the University of Florida
      were included. Demographics, risk factors, tumor features, and outcome data were
      analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate
      analyses, and Kaplan Meier method were used. HER2 expression determined by
      immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or
      positive (3+). RESULTS: Among 49 sequential patients (41 M/8 F) with matched-pair
      tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49
      had near pCR or not enough tumor (NET) to examine in the post- treatment samples.
      Patients with initial HER2 negativity demonstrated conversion to HER2 positivity
      after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more
      common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in
      stages IIB, III) and did not correlate with treatment response or survival.
      CONCLUSIONS: Although limited by a relatively small sample size, our study failed
      to demonstrate that baseline HER2 protein over-expression in EGA predicts
      response to standard CRT. However, our data suggested that HER2 was up regulated
      by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and
      post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably
      reflect the HER2 status of persistent or recurrent disease.

PMID- 27034781
TI  - AKT expression is associated with degree of pathologic response in adenocarcinoma
      of the esophagus treated with neoadjuvant therapy.
AB  - BACKGROUND: Neoadjuvant chemoradiation (NCRT) has become standard in the
      treatment of locally advanced esophageal adenocarcinoma (EAC) with survival
      correlated to degree of pathologic response. The phosphatidyl inositol 3 kinase
      (PI3K)/protein kinase B (AKT)/mTOR pathway plays an important role in
      tumorgenesis and resistance. We sought to elucidate the role of this pathway in
      patients with EAC who received NCRT. METHODS: After IRB approval, a prospective
      trial was initiated in which patients with EAC underwent endoscopic biopsies of
      normal and tumor tissue prior to instituting NCRT. Patients then proceeded to
      esophagectomy. The pre-treatment tissues underwent gene expression profiling. SAM
      method was used to analyze expression of AKT within normal and tumor tissue.
      Expression was then correlated to degree of pathologic response. RESULTS: One
      hundred patients were consented for the study, of which 67 met final eligibility.
      Nineteen patient's tumors ultimately underwent gene expression profiling via
      microarray. The differential expression of all AKT isoforms in tumor tissue was
      markedly overexpressed compared to normal tissue (P=6*10(-5)). There were 3
      patients designated as pNR, 6 as pPR, and 10 as pCR. Partial and non-responders
      had higher expressions of AKT compared to pCR with the non-responders
      consistently illustrated the highest expression of AKT (P=0.02). There was a
      significant correlation between individual isoforms of AKT-1, AKT-2, and AKT-3
      and degree of pathologic response (P=0.002, 0.04, and 0.04 respectively).
      CONCLUSIONS: AKT is overexpressed in patients with AC of the esophagus. Moreover,
      pathologic response to NCRT may be correlated with degree of AKT expression.
      Additional data is needed to clarify this relationship to potentially add
      targeted therapies to the neoadjuvant regimen.

PMID- 27034784
TI  - Drain amylase aids detection of anastomotic leak after esophagectomy.
AB  - BACKGROUND: Anastomotic leak following esophagectomy is associated with
      significant morbidity and mortality. As hospital length of stay decreases, the
      timely diagnosis of leak becomes more important. We evaluated CT esophagram,
      white blood count (WBC), and drain amylase levels in the early detection of
      anastomotic leak. METHODS: The diagnostic performance of CT esophagram, drain
      amylase >800 IU/L, and WBC >12,000/uL within the first 10 days after surgery in
      predicting leak at any time after esophagectomy was calculated. RESULTS:
      Anastomotic leak occurred in 13 patients (13%). CT esophagram performed within 10
      days of surgery diagnosed six of these leaks with a sensitivity of 0.54.
      Elevation in drain amylase level within 10 days of surgery diagnosed anastomotic
      leak with a sensitivity of 0.38. When the CT esophagram and drain amylase were
      combined, the sensitivity rose to 0.69 with a specificity of 0.98. WBC elevation
      had a sensitivity of 0.92, with a specificity of 0.34. Among 30 patients with
      normal drain amylase and a normal WBC, one developed an anastomotic leak.
      CONCLUSIONS: Drain amylase adds to the sensitivity of CT esophagram in the early
      detection of anastomotic leak. Selected patients with normal drain amylase levels
      and normal WBC may be able to safely forgo CT esophagram.

PMID- 27034785
TI  - Changes in neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios during
      chemoradiation predict for survival and pathologic complete response in
      trimodality esophageal cancer patients.
AB  - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio
      (PLR) predict for survival in cancer patients. In patients receiving
      multimodality therapy, the effect of therapy on the NLR and PLR is not well
      understood. We evaluated changes in NLR and PLR among locally advanced esophageal
      cancer patients who received trimodality therapy. METHODS: We performed a
      retrospective analysis of nonmetastatic patients with esophageal cancer who
      received neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy at
      our institution between March 2000 and April 2012. NLR and PLR values were
      obtained for the following time points (TPs): (I) at diagnosis before CRT; (II)
      after CRT but prior to surgery; and (III) after surgery. We evaluated changes in
      NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was
      evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression
      models were applied to evaluate the independent prognostic significance of NLR
      and PLR. RESULTS: This IRB-approved study included the records of 83 consecutive
      patients with stage II-IV esophageal cancer. The median age was 60 years, and
      median follow-up was 29.3 months. Patients were treated to a median prescription
      dose of 50.4 Gy (range, 50.4-56.4 Gy) in 28-33 fractions. Median NLR and PLR were
      3.3 and 157.2, 12 and 645, and 11.5 and 391.7 at TPs 1, 2, and 3, respectively.
      On multivariate analysis, superior OS was associated with PLR >=250 at TP3
      (P=0.03), PLR decrease >=609.2 between TP2 and TP3 (P=0.02), and PLR ratio
      (TP3/TP1) >=1.08 (P=0.03). Inferior progression-free survival (PFS) was
      associated with NLR >=36 at TP2 (P=0.0008), NLR increase >=28.3 between TP1 and
      TP2 (P=0.0005), and PLR ratio (TP2/TP3) >=0.38 (P=0.1). Pathologic complete
      response (PCR) was less likely for adenocarcinoma (AC) histology (P=0.03), NLR
      >=10.6 at TP2 (P=0.04), and NLR increase >=4.6 from TP1 to TP2 (P=0.03).
      CONCLUSIONS: To our knowledge, this is the first study to examine NLR and PLR
      values at various time intervals throughout treatment and demonstrate a
      correlation between OS, PFS, and PCR in patients undergoing trimodality therapy
      for esophageal cancer.

PMID- 27034779
TI  - Designing phase 3 sepsis trials: application of learned experiences from critical
      care trials in acute heart failure.
AB  - Substantial attention and resources have been directed to improving outcomes of
      patients with critical illnesses, in particular sepsis, but all recent clinical
      trials testing various interventions or strategies have failed to detect a robust
      benefit on mortality. Acute heart failure is also a critical illness, and
      although the underlying etiologies differ, acute heart failure and sepsis are
      critical care illnesses that have a high mortality in which clinical trials have
      been difficult to conduct and have not yielded effective treatments. Both
      conditions represent a syndrome that is often difficult to define with a wide
      variation in patient characteristics, presentation, and standard management
      across institutions. Referring to past experiences and lessons learned in acute
      heart failure may be informative and help frame research in the area of sepsis.
      Academic heart failure investigators and industry have worked closely with
      regulators for many years to transition acute heart failure trials away from
      relying on dyspnea assessments and all-cause mortality as the primary measures of
      efficacy, and recent trials have been designed to assess novel clinical composite
      endpoints assessing organ dysfunction and mortality while still assessing all
      cause mortality as a separate measure of safety. Applying the lessons learned in
      acute heart failure trials to severe sepsis and septic shock trials might be
      useful to advance the field. Novel endpoints beyond all-cause mortality should be
      considered for future sepsis trials. 

PMID- 27034786
TI  - The relationship between pathologic nodal disease and residual tumor viability
      after induction chemotherapy in patients with locally advanced esophageal
      adenocarcinoma receiving a tri-modality regimen.
AB  - BACKGROUND: A complete pathologic response to induction chemo-radiotherapy (CRT)
      has been identified as a favorable prognostic factor for patients with loco
      regionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastro
      esophageal junction (E/GEJ). Nodal involvement at the time of surgery has been
      found to be prognostically unfavorable. Less is known, however, about the
      prognostic import of less than complete pathologic regression and its
      relationship to residual nodal disease after induction chemotherapy. METHODS:
      Between February 2008 and January 2012, 60 evaluable patients with ACA of the
      E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post
      operative CRT. Eligibility required a clinical stage of T3-T4 or N1 or M1a (AJCC
      6(th)). Induction chemotherapy with epirubicin 50 mg/m(2) d1, oxaliplatin 130
      mg/m(2) d1, and fluorouracil 200 mg/m(2)/day continuous infusion for 3 weeks, was
      given every 21 days for three courses and was followed by surgical resection.
      Adjuvant CRT consisted of 50-55 Gy at 1.8-2.0 Gy/d and two courses of cisplatin
      (20 mg/m(2)/d) and fluorouracil (1,000 mg/m(2)/d) over 4 days during weeks 1 and
      4 of radiotherapy. Residual viability (RV) was defined as the amount of remaining
      tumor in relation to acellular mucin pools and scarring. RESULTS: Of the 60
      evaluable patients, 54 completed induction therapy and underwent curative intent
      surgery. The Kaplan-Meier projected 3-year overall survival (OS) for patients
      with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%,
      57%, 35%, and 0% respectively (P<0.001). The Kaplan-Meier projected 3-year OS of
      patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%,
      n=9) residual tumor viability was 67%, 42%, and 17% respectively (P=0.004). On
      multivariable analysis (MVA), both the pN descriptor and RV were independently
      prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was
      prognostic for OS [3-year OS 85% (0-25% viable) vs. 51% (>25% viable), P=0.028].
      Outcomes were poor, however, for patients with advanced nodal disease (N2/N3)
      regardless of RV [3-year OS 20% (0-25% viable) vs. 21% (>25% viable), P=0.55].
      CONCLUSIONS: RV and the pN descriptor after induction chemotherapy are
      independent pathologic prognostic factors for OS in patients with LRA ACA of the
      E/GEJ. Patients with extensive nodal disease, however, have poor outcomes
      irrespective of residual tumor viability.

PMID- 27034787
TI  - Perioperative outcomes associated with robotic Ivor Lewis esophagectomy in
      patient's undergoing neoadjuvant chemoradiotherapy.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy (NCR) for the treatment of esophageal
      cancer has been associated with increased perioperative morbidity and mortality.
      Minimally invasive procedures utilizing robotic techniques have been shown to
      reduce perioperative complications and length of hospitalization (LOH). The
      purpose of this study is to compare perioperative outcomes between patients
      undergoing NCR and robotic-assisted Ivor Lewis esophagectomy (RAIL) versus
      upfront RAIL. METHODS: A database of esophagectomy patients was queried to
      identify RAIL patients. Differences in perioperative outcomes were analyzed
      between NCR and non NCR patients. RESULTS: Eighty-nine patients were identified
      who underwent RAIL Seventy-seven patients (87%) had NCR and 22 patients did not
      (13%). The median age was 66 (range, 44-83). The median age of the patients
      treated with NCR was younger {69 [44-83] vs. 64 [46-81] years respectively,
      P=0.05}. The patients who underwent NCR had a higher BMI then those who went
      straight to esophagectomy (31 vs. 27; P=0.001). There were no conversions to open
      laparotomy or thoracotomy in either group. There were no statistically
      significant differences in the mean operative times and estimated blood loss
      (EBL) between both groups. Complications occurred in 17 (19.1%) patients. There
      were no statistically significant differences in the rates of any complications
      between patients receiving NCR and those that did not receive NCR (P=0.11). There
      were no deaths in either group. The total number of days in hospital and total
      number of intensive care unit (ICU) days were also similar in both groups
      (P=0.25). There was no statistically significant difference in the mean number of
      lymph nodes harvested in the patients treated with NCR compared with those
      treated without NCR. CONCLUSIONS: We have demonstrated that RAIL is a safe and
      feasible option for patients with esophageal cancer. The administration of NCR to
      RAIL did not result in an increase in perioperative morbidity and mortality. The
      number of lymph nodes harvested and the completeness of resection was also
      similar between patients who received NCR and those who did not. Longer follow-up
      is required in order to determine long term oncologic outcome.

PMID- 27034788
TI  - Variation of tumoral marker after radiofrequency ablation of pancreatic
      adenocarcinoma.
AB  - BACKGROUND: To evaluate the correlation between variations of CA 19.9 blood
      levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of
      unresectable pancreatic adenocarcinoma. METHODS: In this study, from June 2010 to
      February 2014, patients with diagnosis of unresectable and not metastatic
      pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with
      RFA procedure were included. All these patients underwent RFA. CT study was
      performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month
      after RFA. Features of necrosis at CT, as mean entity, density and necrosis
      percentages compared to the original lesion, were evaluated and compared by using
      t-test with CA 19.9 blood levels variations after RFA procedure. RESULTS: In this
      study were included 51 patients with diagnosis of unresectable and not metastatic
      pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with
      RFA procedure and with CT study and CA 19.9 available for analysis. After the
      procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51
      (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the
      tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24
      (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more
      than 30% in 16/24 (67%). At CT scan necrotic area density difference was not
      statistically significant. Also there was no statistically significant difference
      among the mean area, the mean volume and the mean ablation volume in percentage
      related to the treated tumor among the three different groups of patients divided
      depending on the CA 19.9 blood levels. But a tendency to a statistically
      significant difference was found in comparing the mean percentage of ablation
      volume between two subgroups of patients with a decrease of CA 19.9 levels with
      less or more than 20% reduction of tumor markers and between two subgroups with
      less or more than 30% reduction of CA 19.9 levels. CONCLUSIONS: RFA of
      unresectable pancreatic adenocarcinoma induces reduction of CA 19.9 blood levels
      in about half of the cases.

PMID- 27034789
TI  - Histopathologic tumor response after induction chemotherapy and stereotactic body
      radiation therapy for borderline resectable pancreatic cancer.
AB  - BACKGROUND: While clinical outcomes following induction chemotherapy and
      stereotactic body radiation therapy (SBRT) have been reported for borderline
      resectable pancreatic cancer (BRPC) patients, pathologic response has not
      previously been described. METHODS: This single-institution retrospective review
      evaluated BRPC patients who completed induction gemcitabine-based chemotherapy
      followed by SBRT and surgical resection. Each surgical specimen was assigned two
      tumor regression grades (TRG), one using the College of American Pathologists
      (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria.
      Overall survival (OS) and progression free survival (PFS) were correlated to TRG
      score. RESULTS: We evaluated 36 patients with a median follow-up of 13.8 months
      (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%)
      was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy
      (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular
      involvement. The margin-negative resection rate was 97.2%. Improved response
      according to MDACC grade trended towards superior PFS (P=061), but not OS. Any
      neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was
      associated with improved OS and PFS (both P=0.019). We found no relationship
      between CAP score and OS or PFS. CONCLUSIONS: These data suggest that the
      increased pathologic response after induction chemotherapy and SBRT is correlated
      with improved survival for BRPC patients.

PMID- 27034790
TI  - Patient and caregiver awareness of pancreatic cancer treatments and clinical
      trials.
AB  - BACKGROUND: The poor prognosis of pancreatic cancer has been well established.
      For many patients, active treatments can improve patient outcomes, such as
      overall survival and symptom control. Nevertheless, there is evidence that
      pancreatic cancer is undertreated, even in patients with resectable disease. In
      addition, although participation in a clinical trial is recommended by current
      pancreatic cancer treatment guidelines, recent data suggest that patient
      participation in ongoing trials is below overall target accrual. METHODS: A
      survey was prepared and distributed to patients with pancreatic cancer and
      caregivers of patients with pancreatic cancer by the Pancreatic Cancer Action
      Network (funding for the survey was provided by Celgene Corporation). The 70
      question survey was completed between July 30, 2013, and September 18, 2013, by
      respondents in the United States. The goal of this analysis was to evaluate
      patient and caregiver interactions with physicians about pancreatic cancer
      treatments and participation in clinical trials. RESULTS: The survey was
      completed by 184 patients and 213 caregivers (not necessarily paired). Quality of
      life, extension of survival, and symptom management were identified as the most
      important concerns among both patients and caregivers. A large majority of
      respondents (94.9%) reported that the patient followed the physician's treatment
      recommendation. Approximately 30% of respondents indicated that the diagnosing
      physician offered treatment options at the time of diagnosis. Among the
      respondents who indicated that the physician did not offer treatment options at
      diagnosis, 20.4% stated that no doctor had ever spoken to them about treatment
      options. Most respondents (83.1%) reported that the patient received chemotherapy
      for pancreatic cancer. Approximately half of respondents (49.1%) indicated that
      they had never discussed clinical trials with a physician. Twelve percent of
      respondents reported that the patient participated in a clinical trial. In those
      cases, physicians were listed as the primary source of trial information 80.4% of
      the time. Familiarity with Patient Central (known as "Patient and Liaison
      Services" at the time of the study), a support service offered by the Pancreatic
      Cancer Action Network, was associated with higher rates of receiving treatment
      (P<0.05), searching the Internet for information on clinical trials (P<0.05), and
      participating in clinical trials (not statistically significant). CONCLUSIONS:
      The results of this study suggest that large numbers of patients and caregivers
      had never had discussions with physicians about pancreatic cancer treatments or
      clinical trials. The point about trials takes on even greater importance,
      considering that patients who participate in clinical trials report better
      outcomes than those receiving the same treatment outside of clinical trials.
      Increased discussions with patients could potentially increase treatment and
      trial participation, possibly improving patient- and caregiver-stated priorities
      of quality of life, extension of survival, and symptom management.

PMID- 27034791
TI  - Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Combination chemotherapy regimens including fluoropyrimidines as well
      as albumin-bound paclitaxel have shown promising results in patients with
      metastatic pancreatic adenocarcinoma (mPC). Based on the recently described
      excellent therapeutic index of capecitabine plus nab-paclitaxel in metastatic
      breast cancer, the present phase II trial was initiated. METHODS: Patients with
      previously untreated mPC were treated with capecitabine (825 mg/m(2) orally bid
      on days 1-15) and nab-paclitaxel (125 mg/m(2) intravenously on days 1 and 8)
      every 3 weeks. In patients without clinically relevant adverse reactions after
      the 1st treatment course (<= grade 2 toxicities according to NCI-CTC vs. 4.0,
      exuding alopecia and fatigue of any degree) and adequate bone marrow function,
      the nab-paclitaxel dose was escalated to 100 mg/m(2) on days 1, 8 and 15 of each
      cycle; this intra-individual dose escalation was maintained during subsequent
      treatment courses if tolerated. The primary endpoint was objective response rate
      (ORR) according to RECIST criteria, assessed by an independent radiological
      review committee with evaluation performed every 2 months. RESULTS: Between
      12/2013 and 01/2015, 30 patients were entered in this monocentric academic phase
      II trial. All patients had an ECOG performance status of 0-1, 80% had liver
      metastases and 23% had biliary stents in place at time of study initiation.
      Median CA19-9 was 1,004 U/mL (0.9-100.000 U/mL). In all patients except 2, a dose
      escalation of nab-paclitaxel after the 1st treatment course could be
      accomplished. The most common grade 3 adverse events (AEs) included transient
      sensory neuropathy (23%), (afebrile) neutropenia (17%), hand-foot-syndrome (13%)
      and phototoxic skin reaction (10%). Among 29 RECIST-response assessable patients,
      the ORR was 41.4% and stable disease (SD) was noted in 34.5%, resulting in a
      disease control rate (DCR) of 76%. After a median follow-up duration of 10.3
      months (range, 1.9-19.0 months), 13/30 patients (43.3%) are presently being
      alive. CONCLUSIONS: The combination of capecitabine + nab-paclitaxel at these
      doses and scheduling was well tolerated and showed substantial antitumor
      efficacy.

PMID- 27034792
TI  - Impact of margin status and lymphadenectomy on clinical outcomes in resected
      pancreatic adenocarcinoma: implications for adjuvant radiotherapy.
AB  - BACKGROUND: Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic
      ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the
      clinical significance of margin clearance distance and lymph node (LN)
      parameters, such as extent of dissection and LN ratio. We assessed the impact of
      these variables on clinical outcomes to more clearly define the subset of
      patients who may benefit from adjuvant radiotherapy (RT). METHODS: We identified
      106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were
      categorized as positive (tumor at ink), <=1, or >1 mm. LN evaluation included
      total number examined (NE), number of positive nodes (NP), ratio of NP to NE
      (NR), extent of dissection, and positive periportal LNs. The impact of these
      variables was assessed on disease-free survival (DFS) and overall survival (OS)
      using multivariate cox proportional hazards modeling. RESULTS: In patients
      receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to
      improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE
      was not associated with DFS or OS, yet absolute NP of 5 or more was associated
      with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did
      not result in improved DFS or OS, patients with positive periportal LN had worse
      clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was
      associated with improved OS (P=0.049; HR=0.29). CONCLUSIONS: In patients
      receiving adjuvant CT alone, there was a clinically significant benefit to
      clearing the surgical margin beyond tumor at ink. Having >=5 NP and positive
      periportal LN led to significantly worse clinical outcomes. The addition of
      adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of
      resection margin distance and LN parameters may identify more patients at risk
      for locoregional failure who may benefit from adjuvant CRT.

PMID- 27034793
TI  - Neoadjuvant chemoradiation followed by orthotopic liver transplantation in
      cholangiocarcinomas: the emory experience.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis.
      The median survival after radiotherapy of unresectable disease is 9-12 months.
      The following is a review of our experience with neoadjuvant (NEO) chemoradiation
      followed by orthotopic liver transplantation (OLT) for CCA. METHODS: Ten patients
      with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients
      with unresectable CCA above the cystic duct without intra or extrahepatic
      metastases were eligible. Primary sclerosing cholangitis (PSC) patients were
      included due to their poor resection response. Patients initially received
      external-beam radiation [via conventional fields or volumetric-modulated arc
      therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by
      either Iridium(192) (Ir(192)) brachytherapy high dose rate (HDR) or external
      boost. 5-FU or XEL was administered until OLT. Patients underwent periodic
      surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included
      actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control
      (LC) at 6, 12, and 24 months. RESULTS: Five males and five females were
      identified. Mean age was 58.3 years (range, 38-71 years). Mean composite
      radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of
      patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two
      patients were excluded from the analysis as they did not go on to OLT due to
      metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT
      patients had a pathological complete response (pCR) after NEO, while 25% required
      a Whipple due to positive margins. Median follow-up for the OLT group was 23
      months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was
      100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty
      four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2
      months (95% CI: 22.8-37.7). OS CR was 75% at longest interval (37 months). Post
      OLT mortality resulted from (I) unknown causes (0.5 months), (II) allograft
      rejection (27.25 months). Other toxicities included: necrotic myelitis 12/10
      months after NEO/OLT (n=1), post NEO biliary stricture requiring new stent (n=1);
      post Whipple bile leak repair (n=1), and post OLT fistula (n=1), cholangitis
      (n=1), and wound revision (n=2). CONCLUSIONS: Our outcomes using NEO-OLT for CCA
      are promising and comparable to other series. These results further justify (I)
      use of NEO and (II) prioritization of available transplant livers for CCA
      management.

PMID- 27034794
TI  - Percutaneous "Y" biliary stent placement in palliative treatment of type 4
      malignant hilar stricture.
AB  - BACKGROUND: This study evaluated the technical and clinical efficacy of
      percutaneous bilateral biliary stent-in-stent (SIS) deployment technique with a
      "Y" configuration using open-cell-design stents in type 4 Klatskin tumor
      patients. METHODS: Retrospective evaluation ten patients with type IV Bismuth
      malignant hilar stricture (MHS) treated with percutaneous bilateral "Y" SIS
      deployment technique placement followed in our institution between March of 2012
      and November of 2014. RESULTS: Bilateral SIS deployment was technically
      successful in all patients. One patient (10%) had major complications (episode of
      cholangitis); one patient (10%) had minor complications, including self-limiting
      hemobilia. Successful internal drainage was achieved in nine (90%) patients.
      Stent occlusion by tumor overgrowth and sludge formation occurred in two patient
      (20%). The median survival and stent patency time were 298 and 315 days
      respectively. CONCLUSIONS: Percutaneous bilateral metal stenting using a Y-stent
      is a valid option for the palliative treatment of type 4 Bismuth MHS, improving
      quality patient' life.

PMID- 27034795
TI  - Multimodality therapy of rectal gastrointestinal stromal tumors in the era of
      imatinib-an Indian series.
AB  - BACKGROUND: Primary objective was to determine if sphincter preservation is
      possible with the use of neoadjuvant imatinib in cases of rectal gastrointestinal
      stromal tumor (GIST). Secondary objectives were to determine clinicopathological
      characteristics and intermediate term oncological outcomes of the cases of rectal
      GIST. METHODS: This is a retrospective review of 13 cases of GIST of the rectum
      diagnosed between January 1, 2010 and June 30, 2015 at Tata Memorial Centre,
      Mumbai, India. Clinical parameters that were assessed were duration of the
      neoadjuvant imatinib therapy, type of surgery performed as well as perioperative
      morbidity. Pathological parameters that were assessed included the size of the
      tumor, completeness of resection, mitotic count and mutational analysis. RESULTS:
      Of the 13 patients included, 11 were nonmetastatic at the time of presentation.
      All the patients received neoadjuvant imatinib in view of locally advanced nature
      of the tumors. Median distance from anal verge was 2 cm. Median duration of
      imatinib was 9 months. Of the 9 patients who underwent surgery, three had
      sphincter preserving surgery (33%) whereas the rest had abdomino-perineal
      resection. Two patients had perineal wound infections. All the operated patients
      received adjuvant imatinib therapy for 3 years. Median follow up period was 34
      months. One patient developed distant metastasis; otherwise rest had no local or
      distant recurrence. CONCLUSIONS: In cases of rectal GIST, sphincter preservation
      may not be possible in spite of neoadjuvant therapy with imatinib.

PMID- 27034796
TI  - Prognostic significance of neutrophil-lymphocyte ratio and platelet-lymphocyte
      ratio in patients treated with selective internal radiation therapy.
AB  - BACKGROUND: Elevated neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte
      ratios (PLR) may represent markers of a suboptimal host immune response to cancer
      and have been shown to correlate with prognosis in multiple tumor types across
      different treatment modalities, including radiation therapy. Limited data suggest
      that NLR may predict for survival and disease control in patients receiving
      selective internal radiation therapy (SIRT). The correlation between clinical
      outcomes and change in NLR and PLR after SIRT has not been evaluated. METHODS: We
      retrospectively reviewed 339 consecutive patients with primary (n=37) or
      metastatic (n=79) liver cancer treated with SIRT from 2006 to 2014. Complete
      blood counts with differential were available for 116 patients both before and
      after (median, 29 and 20 days, respectively) SIRT. Survival and progression were
      calculated from date of initial SIRT. Patient and tumor characteristics evaluated
      for ability to predict overall survival (OS) and progression free survival (PFS)
      included pre- and post-treatment neutrophil, platelet, and lymphocyte counts
      (LCs), as well as NLR, PLR, and relative change in NLR and PLR. Cutoff values
      were determined for variables that were significant on multivariate analysis
      (MVA) for OS and/or PFS. RESULTS: Median follow-up of surviving patients was 12
      months. Median OS was 8 months from SIRT and 20 months from date of liver
      metastasis diagnosis. Significant factors on univariate analysis (UVA) for both
      lower OS and PFS included higher post-treatment neutrophil count (NC), higher
      post-treatment NLR, higher liver tumor volume, higher percentage liver tumor
      burden, and worse Eastern Cooperative Oncology Group (ECOG) performance status.
      Significant factors on MVA for lower OS and PFS were ECOG performance status >=2,
      higher liver tumor volume, higher pretreatment PLR, and increase in PLR after
      SIRT. Post-treatment increase in PLR >3-fold was the most predictive early marker
      for increased risk of death when compared with those whose PLR did not increase
      or increased <3-fold. Pretreatment PLR >78 was the most predictive serum marker
      associated with improved OS prior to therapy. CONCLUSIONS: This is the largest
      study to evaluate the association between NLR and PLR with clinical outcomes in
      patients receiving SIRT, with results that confirm that pre- and/or post
      treatment NLR and/or PLR are predictive of clinical outcomes. The largest
      increase in risk of death as well as local and extrahepatic disease progression
      was related to change in PLR, a datum not well reported in the literature. The
      impact of SIRT on blood count changes and the underlying implications of these
      ratios should be further characterized in a prospective study.

PMID- 27034797
TI  - Expression of SPARC like protein 1 (SPARCL1), extracellular matrix-associated
      protein is down regulated in gastric adenocarcinoma.
AB  - BACKGROUND: SPARC-like protein 1 (SPARCL1/Hevin), a member of the SPARC family is
      defined by the presence of a highly acidic domain-I, a follistatin-like domain,
      and an extracellular calcium (EC) binding domain. SPARCL1 has been shown to be
      down-regulated in many types of cancer and may serve as a negative regulator of
      cell growth and proliferation. METHODS: Both tumor and adjacent normal tissue
      were collected from patients with gastric adenocarcinoma. Monoclonal antibody
      developed against recombinant SPARCL1 was used to analyze the expression of
      SPARCL1 by immunohisto chemical and western blotting (WB) analysis. RESULTS: The
      expression of SPARCL1 was found to be significantly lower or negligible in
      gastric adenocarcinoma tissues in nearly all of the cases in comparison with
      adjacent normal tissue. This comparison was found to be independent of the
      patient's age, sex, and stage of cancer. CONCLUSIONS: We postulate that down
      regulation of SPARCL1 may be related to inactivation of its tumor suppressor
      functions and might play an important role in the development of gastric
      adenocarcinoma.

PMID- 27034798
TI  - Metastatic colorectal cancer presenting with bone marrow metastasis: a case
      series and review of literature.
AB  - With advances in treatment, patients with metastatic colorectal cancer (CRC) are
      now living longer with an apparent increase in the incidence of bone and bone
      marrow metastases (BMM). Common sites of metastatic disease from CRC include the
      liver and lungs with bone metastasis rarely occurring in the absence of visceral
      metastatic disease. We report a series of three patients presenting with isolated
      bone and BMM leading to a diagnosis of primary CRC. We have reviewed the
      literature regarding diagnosis, potential mechanisms leading to the development
      of osseous metastasis and outcome. A high level of clinical suspicion and in
      depth understanding of the natural history of these rare metastases may guide
      future management and treatment decisions. 

PMID- 27034799
TI  - Management of the right hepatic artery in pancreaticoduodenectomy: a systematic
      review.
AB  - BACKGROUND: The right hepatic artery (RHA) is the most common hepatic artery
      (CHA) variation. This variation may be problematic in pancreaticoduodenectomy
      (PD). We aimed to evaluate the impact of the RHA on postoperative and oncological
      outcomes. METHODS: The PubMed database was systematically searched for
      comparative studies reporting management of the RHA during PD for the years 1950
      2014. RESULTS: A total of 2,278 patients were analyzed, of whom 440 (19%) had a
      RHA. The most CHA variation was a replaced RHA. The conservative approach was the
      most frequently adopted (87%) and only 8% of patients had a sacrifice without
      reconstruction of the RHA. Postoperative mortality and overall morbidity were
      similar between patients with and without RHA. Despite the preservation of the
      RHA in most cases, the rates of microscopic positive margin were also comparable
      between two groups with no impact of RHA on survival rates. CONCLUSIONS:
      Postoperative and oncological outcomes seemed unaffected by the RHA in PD.
      Prospective studies are needed to evaluate its oncological impact.

PMID- 27034800
TI  - Widespread osteoblastic metastases and marked elevation of CA19-9 as a
      presentation of signet ring cell gastric carcinoma.
AB  - Widespread osteoblastic metastases, as well as marked elevations of CA19-9 and
      carcino-embryonic antigen (CEA), are the initial manifestations of gastric signet
      ring cell carcinoma. CT Imaging revealed diffuse sclerotic metastases in the
      axial skeleton. It was only following gastric biopsy that the primary site of
      metastatic bone tumor was identified. Recent studies suggest that early diagnosis
      of cancer origin, including tumor molecular profiling, may dictate specific
      therapy, improve prognosis and increase patient survival rates. 

PMID- 27034801
TI  - Recognizing the distinct cytomorphologic features of solid pseudopapillary
      neoplasm of the pancreas.
AB  - Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare low-grade
      malignant tumor with an indolent clinical course and a favorable prognosis that
      is most commonly seen in young women of reproductive age. We present a case of
      SPN in a middle-aged man, diagnosed on a limited cytology specimen.
      Interestingly, this tumor has unique cytomorphologic findings in fine needle
      aspiration cytology smears, which help distinguish it from other pancreatic
      lesions. The presence of fibrovascular cores lined by loosely cohesive
      monomorphic neoplastic cells is a reliable cytomorphologic feature on aspiration
      cytology. Recognition of this characteristic finding is crucial for the diagnosis
      of this entity, especially when it presents in unexpected patient populations or
      when faced with scant cytology specimens. This report focuses on the
      distinguishing characteristics of SPN and how they compare and contrast with
      other pancreatic lesions that are in the differential diagnosis of SPN. 

PMID- 27034802
TI  - Use of molecular studies for treatment of metastatic pleomorphic large cell
      pancreatic cancers-a novel strategy.
AB  - Pleomorphic large cell pancreatic cancer is a rare and more aggressive variant
      with no proven treatment in the metastatic setting. It constitutes about 1% of
      the total pancreatic cancer cases. In the absence of any standard of care, we aim
      to increase awareness amongst clinical practitioners that molecular level
      testing, using immunohistochemistry, next-generation sequencing and chromogenic
      in-situ hybridization can help in making chemotherapeutic decisions for this
      variant of pancreatic cancer. We present a 50-year-old male who presented to our
      hospital complaining of persistent abdominal pain. CT scan revealed a pancreatic
      tail mass that was invading the splenic flexure causing high-grade obstruction.
      There was evidence of peritoneal studding. He underwent exploratory laparotomy
      with biopsy of the pancreatic mass and omentum which revealed metastatic
      undifferentiated pleomorphic large cell pancreatic cancer. Since there is no
      proven treatment for this particular entity, his specimen was sent for molecular
      testing. The molecular studies revealed positive mutations of TLE3 gene, EGFR,
      KRAS, PD1 gene, TP53 and TOP2A gene. The tumor was found to be sensitive to
      gemcitabine, paclitaxel, docetaxel, temozolamide, dacarbazine and doxorubicin. He
      was initiated on gemcitabine and nab-paclitaxel. The patient was treated based on
      these recommendations. The patient completed 5 cycles of gemcitabine and nab
      paclitaxel. Treatment had to be held because of gemcitabine induced hemolytic
      uremic syndrome. Serial CT scans have shown stable disease and currently it has
      been 10 months since his diagnosis. Molecular level testing can be an important
      instrument in not only diagnosing but also be an important aid in deciding about
      the chemotherapeutic agents to be used in cases of metastatic pleomorphic large
      cell pancreatic cancer. Availability a knowledge of the novel tools like
      immunohistochemistry, next-generation sequencing and chromogenic in-situ
      hybridization can be prudent and treating some rare forms of pancreatic cancer as
      in this patient. 

PMID- 27034803
TI  - Genomic profiling of high-grade large-cell neuroendocrine carcinoma of the colon.
AB  - High-grade neuroendocrine carcinoma (HGNEC) of the colon is a rare and aggressive
      cancer that has a poor prognosis. Currently no standard treatment exists, and
      published case series report an overall survival of approximately one year with
      treatment. Typically patients receive treatment similar to that recommended for
      small-cell lung cancer, extrapolating from the similarity in cancer biology. Here
      we report a case of HGNEC of the colon with genomic profiling that identified a
      KRAS G12D mutation and a PI3K mutation that has not yet been reported in the
      literature for this tumor type. 

PMID- 27034804
TI  - Metastatic colon cancer from extrahepatic cholangiocarcinoma presenting as
      painless jaundice: case report and literature review.
AB  - Cholangiocarcinoma (CCA) is a rare cancer of the biliary epithelium comprising
      only about 3% of all gastrointestinal malignancies. It is a highly aggressive
      malignancy and confers a dismal prognosis with majority of patients presenting
      with metastatic disease. Metastatic CCA to the colon is extremely rare with only
      few cases reported in the literature. We present a 61-year-old patient with
      incidental synchronous metastatic colonic adenocarcinoma from extra-hepatic CCA.
      Laboratory data revealed significant indirect hyperbilirubinemia and
      transaminitis. Imaging study showed intrahepatic bile ducts prominence without
      mass lesions. Incidentally, there was diffuse colonic thickening without mass
      lesions or obstruction. Endoscopic retrograde cholangiopancreatography (ERCP)
      showed a common bile duct stricture. Brushings were consistent with CCA.
      Screening colonoscopy identified nodularity and biopsy and immunostaining were
      consistent with CCA metastasis to colon. The patient elected for palliative and
      comfort care. Metastatic CCA to the colon is a rare pattern of distant spread
      that may pose a diagnostic challenge. Some salient characteristics may assist in
      the differentiation of primary colon cancer and metastatic colon cancer from CCA.
      Little remains known about the pathogenic behavior of metastatic secondary
      colorectal cancer. And more so, the management approach to such metastatic cancer
      still remains to be defined. Screening colonoscopy in patients presenting with
      resectable CCA may alter management. Furthermore, whether patients with history
      of resected CCA may benefit from a more frequent screening colonoscopy remains to
      be validated. 

PMID- 27034805
TI  - Molecular profiling of a case of advanced pancreatic cancer identifies an active
      and tolerable combination of targeted therapy with backbone chemotherapy.
AB  - Typical survival with common 1(st)-line regimens for pancreatic cancer range from
      6-11 months. We report a case of a patient with stage IVB pancreatic
      adenocarcinoma treated with gemcitabine and erlotinib who stopped therapy after 3
      months without achieving a response due to intolerance. To decide upon additional
      treatment options, molecular analysis was performed on liver metastasis which
      revealed KRAS, FBXW7, APC, and ATM mutations, with thymidylate synthase (TS)
      negativity and PD-1 positivity. Based on this profile of TS negativity and ATM
      mutation, a combination strategy was devised consisting of capecitabine,
      oxaliplatin, bevacizumab and vorinostat. The patient had a near complete response
      to therapy with this regimen. In refractory metastatic pancreatic cancer,
      responses of this magnitude are rarely seen. To our knowledge, this represents
      the first demonstrated activity of this combination in the metastatic setting
      which could prompt further investigation of its use in large scale clinical
      trials. 

PMID- 27034806
TI  - Immune targeting of cancer stem cells in gastrointestinal oncology.
AB  - The cancer stem cell (CSC) hypothesis postulates that a sub-population of
      quiescent cells exist within tumors which are resistant to conventional
      cytotoxic/anti-proliferative therapies. It is these CSCs which then seed tumor
      relapse, even in cases of apparent complete response to systemic therapy.
      Therefore, therapies, such as immunotherapy, which add a specific anti-CSC
      strategy to standard cytoreductive treatments may provide a promising new
      direction for future cancer therapies. CSCs are an attractive target for immune
      therapies since, unlike chemotherapy or radiotherapy, immune effector cells do
      not specifically require target cells to be proliferating in order to effectively
      kill them. Although recent advances have been made in the development of novel
      systemic and targeted therapies for advanced gastro-intestinal (GI) malignancies,
      there remains an unmet need for durable new therapies for these refractory
      malignancies. Novel immunotherapeutic strategies targeting CSCs are in pre
      clinical and clinical development across the spectrum of the immune system,
      including strategies utilizing adaptive immune cell-based effectors, innate
      immune effectors, as well as vaccine approaches. Lastly, since important CSC
      functions are affected by the tumor microenvironment, targeting of both cellular
      (myeloid derived suppressor cells and tumor-associated macrophages) and sub
      cellular (cytokines, chemokines, and PD1/PDL1) components of the tumor
      microenvironment is under investigation in the immune targeting of CSCs. These
      efforts are adding to the significant optimism about the potential utility of
      immunotherapy to overcome cancer resistance mechanisms and cure greater numbers
      of patients with advanced malignancy. 

PMID- 27034807
TI  - Undifferentiated embryonal sarcoma of the liver with an unusual presentation:
      case report and review of the literature.
AB  - Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant
      mesenchymal neoplasm, relatively unique to the liver that occurs primarily in
      children and teenagers. Delay in diagnosis is not uncommon due to lack of a
      characteristic clinical presentation, serological markers and radiological
      changes. We report a case of UESL in a 9-year-old girl who presented with right
      upper quadrant pain and a palpable mass. Laboratory and imaging workup revealed a
      complex hepatic cyst, increased IgE, transient peripheral eosinophilia and a
      normal alpha-fetoprotein (AFP). Initial empirical treatment with albendazole was
      implemented for presumed hydatid cyst disease, but the child failed to improve.
      Subsequent surgical resection resulted in the correct diagnosis of UESL. She
      received 6 months of chemotherapy and remains well with no evidence of tumor
      about 12 months after resection. We herein review the typical clinical,
      radiologic and pathologic features of this rare tumor. 

PMID- 27034808
TI  - Functioning gangliocytic paraganglioma of the ampulla: clinicopathological
      correlations and cytologic features.
AB  - Gangliocytic paraganglioma (GP) is a rare neuroendocrine tumor almost exclusively
      found in the ampulla. It is considered nonfunctioning in the literature. We
      herein report the first case of functioning GP arising in the ampulla. Our
      patient had a constellation of ampullary neuroendocrine tumor, flushing,
      diarrhea, weight loss, diabetes mellitus, and cholelithiasis, consistent with
      effects of serotonin and somatostatin that were overexpressed by the ampullary
      neuroendocrine tumor. The serum serotonin level was elevated. Immunostaining
      confirmed somatostatin expression by the epithelioid cells and ganglion-like
      cells of GP. After surgical resection of the tumor, the patient became
      euglycemic. However, computed tomography (CT) scan 3 months post-surgery showed
      regional lymphadenopathy suspicious for residual/recurrent/metastatic disease. In
      the interim, his flushing and hyperglycemia recurred and worsened. Increased
      awareness about the functioning potential of GP is important so that the
      underlying pathophysiologic link is not overlooked and patients are appropriately
      managed. Moreover, we describe the cytologic features that help make the
      preoperative diagnosis, and these have not been previously described. 

PMID- 27034809
TI  - Molecular testing to optimize therapeutic decision making in advanced colorectal
      cancer.
AB  - Colorectal cancer (CRC) is a leading cause of cancer death in the United States.
      In recent years, therapeutic advances have prolonged the survival of patients
      with advanced disease. Along with the addition of new treatments, an increasing
      body of literature explores the potential benefit of using molecular testing to
      define tumor, circulating, or host biomarkers of benefit to specific treatment
      strategies. At present, testing for specific mutations in exons 2, 3, and 4 of
      KRAS and NRAS has become accepted practice to select patients for treatment with
      epidermal growth factor receptor (EGFR)-targeted agents. Additionally, testing
      for the BRAF V600E mutation is used to refine decisions based on patient
      prognosis. The presence of the uridine diphosphate glucuronosyltransferase 1A1
      (UGT1A1) *28 polymorphism is associated with toxicity from irinotecan, although
      it has not been universally applied. Nonetheless, molecular markers to predict
      response and toxicity of cytotoxic therapy are evolving. While the development of
      selection biomarkers for anti-angiogenic treatments has not proved fruitful to
      date, improved development strategies and novel targeted agents are anticipated
      to revolutionize the approach to treatment of advanced CRC in the near future.
      This review summarizes currently available data to select treatment strategies in
      patients with advanced CRC. 

PMID- 27034810
TI  - Diagnosis and differential diagnosis of hepatic graft versus host disease (GVHD).
AB  - Graft versus host disease (GVHD) is a common complication following allogeneic
      hematopoietic cell transplantation (HCT) that typically manifests as injury to
      the skin, gastrointestinal mucosa, and liver. In some cases, hepatic GVHD may be
      histologically indistinguishable from other disorders such as infection and drug
      induced liver injury (DILI). Additionally, clinical signs and symptoms are
      frequently confounded by the superimposed effects of pretransplant
      chemoradiotherapy, immunotherapy (IT) (targeted to the underlying malignancy),
      GVHD prophylaxis, and infection. Thus, careful attention to and correlation with
      clinical findings, laboratory values, and histologic features is essential for
      diagnosis. This review, aimed at the practicing pathologist, will discuss current
      clinical and histologic criteria for GVHD, the approach to diagnosis of hepatic
      GVHD, and features helpful for distinguishing it from other entities in the
      differential diagnosis. 

PMID- 27034811
TI  - Health disparities in colorectal cancer among racial and ethnic minorities in the
      United States.
AB  - In the 2010 Census, just over one-third of the United States (US) population
      identified themselves as being something other than being non-Hispanic white
      alone. This group has increased in size from 86.9 million in 2000 to 111.9
      million in 2010, representing an increase of 29 percent over the ten year period.
      Per the American Cancer Society, racial and ethnic minorities are more likely to
      develop cancer and die from it when compared to the general population of the
      United States. This is particularly true for colorectal cancer (CRC). The primary
      aim of this review is to highlight the disparities in CRC among racial and ethnic
      minorities in the United States. Despite overall rates of CRC decreasing
      nationally and within certain racial and ethnic minorities in the US, there
      continue to be disparities in incidence and mortality when compared to non
      Hispanic whites. The disparities in CRC incidence and mortality are related to
      certain areas of deficiency such as knowledge of family history, access to care
      obstacles, impact of migration on CRC and paucity of clinical data. These areas
      of deficiency limit understanding of CRC's impact in these groups and when
      developing interventions to close the disparity gap. Even with the implementation
      of the Patient Protection and Affordable Healthcare Act, disparities in CRC
      screening will continue to exist until specific interventions are implemented in
      the context of each of racial and ethnic group. Racial and ethnic minorities
      cannot be viewed as one monolithic group, rather as different segments since
      there are variations in incidence and mortality based on natural history of CRC
      development impacted by gender, ethnicity group, nationality, access, as well as
      migration and socioeconomic status. Progress has been made overall, but there is
      much work to be done. 

PMID- 27034812
TI  - Cutaneous manifestation of gastrointestinal disease.
AB  - The gastrointestinal (GI) and cutaneous systems are closely linked in origin.
      Skin manifestations are frequently seen as a part of different GI syndromes.
      Gastroenterologists play an important role in recognizing the symptoms, patient
      workup and arriving at appropriate diagnoses, often in consultation with
      dermatologists. This review discusses the diseases with both cutaneous and
      intestinal involvement. Hereditary polyposis GI cancers, hereditary nonpolyposis
      colorectal cancers (CRCs), hamartomatous disorders, and inflammatory bowel
      disease (IBD) are reviewed with emphasis on the genetic basis, diagnostic,
      histologic findings, screening modalities, and therapeutic options. 

PMID- 27034813
TI  - Consensus and conflict in invasive micropapillary carcinoma: a case report and
      review of the literature.
AB  - Invasive micropapillary carcinoma (IMPC) is an aggressive histologic subtype of
      adenocarcinoma that has been gaining increased attention over the past twenty
      years. It is important to recognize IMPC due to its strong association with early
      lymphovascular invasion (LVI), high risk of lymph node metastasis, perineural
      invasion and poor prognosis. Controversies regarding IMPC include differentiating
      from retraction artifact and mimics, clinical significance of proportion of
      micropapillary component (MC), pathogenesis, biologic nature of the entity and
      consequently terminology, etc. We herein present a case of rectal IMPC arising
      from a tubulovillous adenoma. Since HER2 over-expression has been reported in
      IMPC of the breast and the bladder but never in the colorectum, given the
      availability of HER2 targeted therapy, HER2 protein expression in our case is
      examined by immunohistochemical study which shows weak incomplete membrane
      staining in less than 5% of cells. Literature is reviewed with emphasis on
      colorectal IMPC as well as aforementioned controversial topics. In summary, more
      study is needed to resolve the conflicts and build consensus on IMPC. 

PMID- 27034814
TI  - Intrapancreatic accessory spleen: utilization of fine needle aspiration for
      diagnosis of a potential mimic of a pancreatic neoplasm.
AB  - Accessory spleen (AS) is not a rare occurrence, and with the second most common
      site being the tail of the pancreas, intrapancreatic AS (IPAS) can easily mimic a
      pancreatic neoplasm. Together with radiologic imaging findings, endoscopic
      ultrasound-guided fine needle aspiration (FNA) can be used to assist in the
      diagnosis, preventing potentially unnecessary surgical procedures. The most
      common cytologic findings that have been described in the literature include a
      heterogenous population of small lymphocytes along with traversing small vessels.
      Immunohistochemical staining for CD8 has also been documented as a useful tool to
      support the diagnosis as it specifically highlights the endothelial cells of the
      splenic sinus. Here, we report two additional cases of IPAS diagnosed by FNA and
      discuss the potential pitfalls in diagnosis of this entity. 

PMID- 27034815
TI  - Merkel cell carcinoma of unknown primary with lymph node and mesenteric
      metastasis involving the pancreas and duodenum.
AB  - Merkel cell carcinoma (MCC) of skin is a rare, aggressive cutaneous malignancy of
      neuroendocrine origin. MCC predominantly affects elderly Caucasians and has high
      predilection for sun exposed areas. Histologic exam and immunohistochemical
      profile is required to establish the diagnosis. It has high propensity for local
      recurrence and metastasis, and carries poor prognosis. However, metastasis to
      mesentery involving the duodenum is very uncommon and rarely reported in
      literature. We hereby describe a patient with lymph node and mesenteric
      metastasis invading duodenum and pancreas with unknown primary origin of MCC. 

PMID- 27034816
TI  - Gastrointestinal stromal tumor with an unusual presentation as an enlarged
      prostate gland: a case report and review of the literature.
AB  - We report a case of a 78-year-old male who presented with urinary retention,
      constipation and an enlarged prostate gland. A transurethral resection of the
      prostate (TURP) was performed. Pathologic examination revealed a hypercellular
      spindled neoplasm with frequent mitoses, nuclear pleomorphism, and multifocal
      geographic tumoral necrosis. A pathologic diagnosis of gastrointestinal stromal
      tumor (GIST) was made based on morphologic and immunohistochemical findings, and
      was later reinforced by molecular study results. This lesion was initially
      thought to represent a primary prostatic GIST. To the best of our knowledge,
      there have been only five cases of primary prostatic GISTs. Subsequent imaging
      studies revealed the mass to be contiguous with the anterior rectal wall,
      suggesting the possibility of a rectal primary with extension to the prostate
      gland. The patient was treated with imatinib mesylate, and after twelve months of
      follow up failed to demonstrate any evidence of progression or metastatic
      disease. GIST should be considered in cases of prostatic tumors with a spindled
      or epithelioid morphology, and immunohistochemistry and possible molecular
      studies are recommended to aid in diagnosis and guide treatment decisions. 

PMID- 27034818
TI  - Pyloric gland adenoma of gallbladder-reports of two cases and a brief review of
      literature.
AB  - Adenomas of the gallbladder are uncommon benign epithelial neoplasms. Rarely,
      they can give rise to gallbladder cancer, which is the most common malignancy of
      the biliary tract, carrying a poor prognosis and decreased survival. Here we
      report the case histories of two patients, 40-year-old and 53-year-old males who
      presented with >1 cm gallbladder polyps, which were detected and confirmed using
      various imaging studies. Cholecystectomy was performed on both patients and the
      subsequent pathologic exam revealed 1.2 and 1.6 cm polyps in the lumen.
      Histopathologically, both polyps showed features reminiscent of "pyloric" gland
      type of adenoma. The differences between the two cases in regard to
      histopathological and immunohistochemical characteristics will be discussed. We
      will also briefly review the latest nomenclature on such low-grade polypoid
      gallbladder entities. 

PMID- 27034817
TI  - Non-pancreatic retroperitoneal mucinous neoplasms and a discussion of the
      differential diagnosis.
AB  - Retroperitoneal mucinous neoplasms are common and have a wide range of
      differential diagnoses to consider. It is of utmost importance to maintain a
      multidisciplinary approach when evaluating these lesions. Clinical history,
      surgical impression and radiographic studies should be obtained and used in
      conjunction with morphology and immunohistochemistry to help guide the
      pathologist to the correct diagnosis. We recently encountered a case of a 51-year
      old man who presented with an 11.5 cm left-sided retroperitoneal mucinous
      neoplasm. This lesion was initially diagnosed as a low-grade mucinous carcinoma
      of probable pancreatic origin at an outside facility, and he was subsequently
      treated with chemotherapy. One year later he presented to our institution and
      underwent retroperitoneal en bloc resection of the 7-cm residual multiloculated
      mucinous neoplasm. When discussed at tumor board additional medical history was
      obtained, and review of the patient's chart revealed a remote history of left
      orchiectomy for a mixed malignant germ cell tumor and metastatic embryonal
      carcinoma in 2 of 34 retroperitoneal/para-aortic lymph nodes. With no clinical
      evidence of tumor in the pancreas or extension from it, the predominately para
      aortic location of the tumor favors a mucinous carcinoma arising from a rest of
      mature metastatic/proliferating teratoma that persisted after chemotherapy. This
      case illustrates the importance of a thorough history, however remote, and
      correlation with imaging in the development of differential diagnoses, as well
      as, the need to consider non-pancreaticobiliary sources of retroperitoneal
      mucinous tumors. 

PMID- 27034819
TI  - Coexistence of intestinal Kaposi sarcoma and plasmablastic lymphoma in an
      HIV/AIDS patient: case report and review of the literature.
AB  - Human immunodeficiency virus (HIV) infection or acquired immunodeficiency disease
      (AIDS) is associated with increased risk for various malignancies including
      Kaposi sarcoma (KS) and lymphoma. We report a rare case of coexistence of KS and
      plasmablastic lymphoma (PBL) in the gastrointestinal (GI) tract in a HIV/AIDS
      patient. A brief review of literature is also presented. 

PMID- 27034820
TI  - A case of peripheral T-cell lymphoma, not otherwise specified in a HCV and HTLV
      II-positive patient, diagnosed by abdominal fluid cytology.
AB  - BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a
      rare neoplasm that typically presents as generalized lymphadenopathy. PTCL, NOS
      presenting as malignant ascites is rare. METHODS: A 61-year-old African-American
      man with past medical history of HCV, cryoglobulinemia, and cryptococcal
      pneumonia was admitted for dyspnea on exertion over a period of 1 month and new
      onset of abdominal distension. RESULTS: Ascites, splenomegaly, hepatomegaly and
      extensive lymphadenopathy were found by imaging. Paracentesis obtained 1.3 liter
      of abdominal fluid, the cytologic evaluation showed a monomorphic population of
      intermediate-sized lymphoid cells with irregular to convoluted nuclear contours.
      Fluid sent for flow cytometry showed an abnormal T-lymphocyte population
      expressing CD4, weak surface CD3 and absence of CD7. PCR studies of ascitic fluid
      detected a clonal T-lymphocyte population with T-cell receptor gamma gene
      rearrangement. Serologic testing for human T lymphotropic virus (HTLV) was
      positive for HTLV-II. Subsequent bone marrow biopsy revealed lymphomatous
      involvement. CD30 and ALK-1 immunostaining were negative. This case was
      classified as PTCL, NOS. CONCLUSIONS: PTCL, NOS can have unusual clinical
      presentation such as ascites and pleural effusion, and may also occur as a
      complication of immunodeficiency state. Further studies are needed to determine
      if HCV or HTLV-II viral infection is associated with PTCL.

PMID- 27034821
TI  - Dealings between Cataract and Retinal Reattachment Surgery in PVR.
AB  - Introduction. To evaluate the impact of the eye lens status and oil side effects
      on the outcome of vitreoretinal surgery in retinal detachment with proliferative
      vitreoretinopathy (PVR) and a temporary silicone oil tamponade (SOT). Methods.
      101 eyes were analyzed retrospectively and 103 eyes prospectively in regard to
      their retinal reattachment success rate and key factors for the outcome. Subgroup
      analysis of 27 eyes with Scheimpflug lens photography (SLP) before and after
      retinal reattachment service with SOT was performed. For SLP (65% phakic eyes) a
      Pentacam densitometry reference body with 3 mm diameter was chosen and 3 segments
      (anterior/mid/posterior) were evaluated separately after a quality check.
      Results. The retinal reattachment rate was highest in the prospective
      pseudophakic group (p = 0.039). Lens transparency loss occurred earlier in middle
      aged patients than in younger patients. Besides the nucleus, layers posterior and
      anterior to it showed specific transparency changes. The emulsification rate was
      higher when eyes had been operated on in the anterior chamber before retinal
      reattachment service. Conclusions. Retinal reattachment surgery seems to benefit
      from preoperative cataract removal. We found significant lens changes in the
      nucleus as well as in the layers anterior and posterior to it. This corresponds
      to the histology of the lens epithelium published before. 

PMID- 27034822
TI  - A Randomized Controlled Trial of Conbercept Pretreatment before Vitrectomy in
      Proliferative Diabetic Retinopathy.
AB  - Purpose. To determine the efficacy and safety of preoperative intravitreal
      conbercept (IVC) injection before vitrectomy for proliferative diabetic
      retinopathy (PDR). Methods. 107 eyes of 88 patients that underwent pars plana
      vitrectomy (PPV) for active PDR were enrolled. All patients were assigned
      randomly to either preoperative IVC group or control group. Follow-up
      examinations were performed for three months after surgery. The primary
      bioactivity measures were severity of intraoperative bleeding, incidence of early
      and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity
      (BCVA) levels. The secondary safety measures included intraocular pressure,
      endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse
      events. Results. The incidence and severity of intraoperative bleeding were
      significantly lower in IVC group than in the control group. The average vitreous
      clear-up time of early recurrent VH was significantly shorter in IVC group
      compared with that in control group. There was no significant difference in
      vitreous clear-up time of late recurrent VH between the two groups. Patients that
      received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1
      month after surgery than control group. Moreover, both patients with improved
      BCVA were greater in IVC group than in control group at each follow-up.
      Conclusions. Conbercept pretreatment could be an effective adjunct to vitrectomy
      in accelerating postoperative vitreous clear-up and acquiring stable visual
      acuity restoration for PDR. 

PMID- 27034823
TI  - A Controlled Study on the Correlation between Tear Film Volume and Tear Film
      Stability in Diabetic Patients.
AB  - Purpose. To assess the tear film quantity and correlate it with the quality and
      stability of the tear film in diabetics and compare them to age matched controls.
      Introduction. Diabetes affects tear film parameters in multiple ways. Poor
      metabolic control and neuropathy are postulated factors. To further understand
      how diabetes affects tear film parameters this study was conducted. Subjects and
      Methods. Tear meniscus height was measured by anterior segment OCT, along with
      tear thinning time, a subtype of noninvasive tear break-up time, and blinking
      rate per minute which were all recorded for 22 diabetic patients. Correlations
      between these tear film parameters were studied and then compared to 16 age
      matched controls. Results. A statistically significant difference was found in
      blinking rate between the diabetic and the control group (P = 0.002), with higher
      blinking rate among diabetics. All tear film parameters were negatively
      correlated with duration of diabetes. A positive correlation was found between
      tear film volume and stability. Conclusion. Diabetes affects the tear film in
      various ways. Diabetics should be examined for dry eye signs even in absence of
      symptoms which may be masked by associated neuropathy. Duration of diabetes has
      an impact on tear film status. 

PMID- 27034824
TI  - Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis.
AB  - Introduction. Th17, gammadeltaT, NK, and NKT cells in peripheral blood and serum
      IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with
      disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK
      (anti-CD3APC, CD56FITC), and gammadeltaT (anti-CD3FITC and gammadeltaTCRAPC)
      cells were enumerated by flow cytometry in peripheral blood of 30 patients with
      TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by
      ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed
      (using nonparametric tests, median with interquartile range). Results. Mean age
      of patients was 33.47 +/- 11.78 years (25 females); mean symptom duration was 7.1
      +/- 5.3 years. 13 were not on immunosuppressants; 12 were active (ITAS2010 >= 4).
      The percentage of Th17 cells was significantly expanded in TA (patients 2.1 (1.5
      3.2) versus controls 0.75 (0.32-1.2); p < 0.0001) with no differences in other
      cell populations. Serum IL-17 and IL-23 (pg/mL) in patients (6.2 (4.6-8.5) and 15
      (14.9-26.5), resp.) were significantly higher (p < 0.001) than controls (3.9 (3.9
      7.3) and undetectable median value, resp.). Subgroup analysis revealed no
      correlation of Th17 cells, serum IL-17, and IL-23 with disease activity or
      medications, nor any significant difference before and after medication.
      Conclusions. There is significant expansion of Th17 cells and elevated serum IL
      17 and IL-23 levels in TA patients compared to healthy controls. 

PMID- 27034825
TI  - Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic
      Response.
AB  - Anemia is the primary clinical manifestation of malarial infections and is
      responsible for the substantial rate of morbidity. The pathophysiology discussed
      till now catalogued several causes for malarial anemia among which ineffective
      erythropoiesis being remarkable one occurs silently in the bone marrow. A
      systematic literature search was performed and summarized information on
      erythropoietic response upon malaria infection and the factors responsible for
      the same. This review summarizes the clinical and experimental studies on
      patients, mouse models, and in vitro cell cultures reporting erythropoietic
      changes upon malaria infection as well as factors accountable for the same.
      Inadequate erythropoietic response during malaria infection may be the collective
      effect of various mediators generated by host immune response as well as parasite
      metabolites. The interplay between various modulators causing the pathophysiology
      needs to be explored further. Globin gene expression profiling upon malaria
      infection should also be looked into as abnormal production of globin chains
      could be a possible contributor to ineffective erythropoiesis. 

PMID- 27034826
TI  - A Structured Assessment to Decrease the Amount of Inconclusive Endometrial
      Biopsies in Women with Postmenopausal Bleeding.
AB  - OBJECTIVE: To determine whether structured assessment of outpatient endometrial
      biopsies decreases the number of inconclusive samples. DESIGN: Retrospective
      cohort study. SETTING: Single hospital pathology laboratory. POPULATION:
      Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected
      during the usual diagnostic work-up and assessed as insufficient for a reliable
      histological diagnosis. METHODS: Endometrial biopsy samples were requested from
      the pathology laboratories. The retrieved samples were systematically reassessed
      by a single pathologist specialized in gynecology. MAIN OUTCOME MEASURE:
      Disagreement between initial assessment and conclusion after structured
      reassessment. RESULTS: We retrieved 36 of 66 endometrial biopsy samples from six
      different pathology laboratories. Structured reassessment of the retrieved
      samples by a single pathologist specialized in gynecology did not change the
      conclusion in 35 of the 36 samples. The remaining sample contained a large amount
      of endometrial tissue and the diagnosis at reassessment was endometrial
      hyperplasia without atypia. All other samples contained insufficient material for
      a reliable diagnosis. CONCLUSION: A structured reassessment of endometrial
      biopsies samples, which were classified as inconclusive due to insufficient
      material, did not change the conclusion. Although it might be helpful for
      pathologists to have diagnostic criteria for adequacy and/or inadequacy of an
      endometrial biopsy sample, the gain in efficiency is likely to be small.

PMID- 27034827
TI  - Recent Clinical Characteristics of Labors Using Three Japanese Systems of Midwife
      Led Primary Delivery Care.
AB  - Objective. The objective of this study was to describe the recent clinical
      characteristics of labor using 3 systems of Japanese midwife-led primary delivery
      care, as follows: (1) those intending to give birth at home managed by midwives
      who do not belong to our hospital, (2) those planning to give birth in our
      hospital managed by the same midwives, and (3) those planning to give birth
      managed by midwives who belong to our hospital. Methods. A retrospective cohort
      study was performed. Results. There were no significant differences in the
      obstetric or neonatal outcomes among the 3 groups. The rate of transfers during
      labor with the system involving midwives belonging to our hospital was higher
      than those with the other 2 systems. In addition, the timing of transfers in the
      system with the midwives belonging to our hospital was earlier than with the
      other 2 systems. Among the 3 groups, there were no significant differences in the
      rate of the main 2 indications for transfers: fetal heart rate abnormality and
      failure to progress. Conclusion. There were no significant differences in
      perinatal outcomes among the 3 systems; however, there were some differences in
      the status of transfers to obstetric shared care. 

PMID- 27034828
TI  - Robot-Assisted Myomectomy for Large Uterine Myomas: A Single Center Experience.
AB  - Objective. To determine if robot-assisted myomectomy (RAM) is feasible for women
      with large uterine myomas. Methods. Retrospective review of one gynecologic
      surgeon's RAM cases between May 2010 and July 2013. Large uterine myomas, defined
      as the largest myoma >=9 cm by preoperative magnetic resonance imaging, was age-
      and time-matched to controls with the largest myoma <9 cm. Primary surgical
      outcomes compared were operative time and estimated blood loss (EBL). Results.
      207 patients were included: 66 (32%) patients were in the >=9 cm group, while 141
      (68%) patients were in the <9 cm group. There was a statistically significant
      increase in the operative time (130 min versus 92 min) and EBL (100 mL versus 25
      mL) for the >=9 cm group compared to the <9 cm group. Ten (4.8%) patients had the
      largest myoma measuring >=15 cm, and 11 (5.3%) patients had a specimen weight
      >900 gm, of which no major adverse outcomes were observed. All patients in the
      study cohort were discharged on the same day after surgery. Conclusion. RAM is a
      feasible surgical approach for patients with myomas >=9 cm. Patients with large
      myomas undergoing RAM are also candidates for same-day discharge after surgery. 

PMID- 27034829
TI  - Thyroid Hormones as Renal Cell Cancer Regulators.
AB  - It is known that thyroid hormone is an important regulator of cancer development
      and metastasis. What is more, changes across the genome, as well as alternative
      splicing, may affect the activity of the thyroid hormone receptors. Mechanism of
      action of the thyroid hormone is different in every cancer; therefore in this
      review thyroid hormone and its receptor are presented as a regulator of renal
      cell carcinoma. 

PMID- 27034830
TI  - Decreased Brain and Placental Perfusion in Omphalopagus Conjoined Twins on Fetal
      MRI.
AB  - The aim of this study is to evaluate perfusional changes in brain and placenta of
      omphalopagus conjoined twins and to compare them with singleton fetuses by using
      diffusion weighted imaging and apparent diffusion coefficient. Fetal MRIs of 28
      week-old omphalopagus conjoined twins with a shared liver with two separate
      gallbladders and portal and hepatic venous systems and three singleton fetuses
      with unilateral borderline ventriculomegaly at the same gestational week as
      control group were enrolled retrospectively. There was a significant decrease in
      ADC values of brain regions (p = 0.018) and placenta (p = 0.005) of conjoined
      twins compared to the control group. The decreased ADC values in placenta and
      brain regions in conjoined twins might be due to decreased placental perfusion
      compared to singleton pregnancy. Our results would be a keystone for future
      studies which will compare larger group of monochorionic multiple pregnancies
      with singleton pregnancies. 

PMID- 27034831
TI  - Diffusion-Weighted Imaging with Color-Coded Images: Towards a Reduction in
      Reading Time While Keeping a Similar Accuracy.
AB  - The aim of this study was to develop a diagnostic tool capable of providing
      diffusion and apparent diffusion coefficient (ADC) map information in a single
      color-coded image and to assess the performance of color-coded images compared
      with their corresponding diffusion and ADC map. The institutional review board
      approved this retrospective study, which sequentially enrolled 36 head MRI scans.
      Diffusion-weighted images (DWI) and ADC maps were compared to their corresponding
      color-coded images. Four raters had their interobserver agreement measured for
      both conventional (DWI) and color-coded images. Differences between conventional
      and color-coded images were also estimated for each of the 4 raters. Cohen's
      kappa and percent agreement were used. Also, paired-samples t-test was used to
      compare reading time for rater 1. Conventional and color-coded images had
      substantial or almost perfect agreement for all raters. Mean reading time of
      rater 1 was 47.4 seconds for DWI and 27.9 seconds for color-coded images (P =
      .00007). These findings are important because they support the role of color
      coded images as being equivalent to that of the conventional DWI in terms of
      diagnostic capability. Reduction in reading time (which makes the reading easier)
      is also demonstrated for one rater in this study. 

PMID- 27034832
TI  - Establishing the Psychometric Properties of the ICOAP Questionnaire through Intra
      Articular Treatment of Osteoarthritic Pain: Implementation for the Greek Version.
AB  - Objectives. In this prospective study, we intend to establish the psychometric
      properties of ICOAP for its use in studies involving the Hellenic population.
      Methods. SF-36 Health Survey was used as a standard against ICOAP scores from a
      sample of 89 patients (mean age: 71.07, 69 females) with hip and knee OA pain who
      underwent 2 treatment cycles of 4 intra-articular injections of sodium
      hyaluronate, separated by a 12-week medication-free time interval. Both
      questionnaires were filled twice with no missing data during follow-up. Results.
      ROC analysis accomplished ICOAP's criterion-related validation. Wilcoxon Signed
      Rank Test and paired samples t-test endorsed ICOAP's responsiveness along with
      Effect Size values, standard response mean, and Relative Efficiency. Comparisons
      between the areas under curves (AUC) on ROC plots established external
      responsiveness. Cronbach's-alpha value favored ICOAP's internal consistency.
      This, along with intraclass correlation, results in both advocated reliability
      and content validity. Interitem discrimination was demonstrated by the ease of
      completion of ICOAP as well as the degree of familiarity with it. These findings
      inaugurated construct validity in collaboration with Spearman's and One-Way ANOVA
      results. Conclusions. ICOAP is a valid, reliable, and responsive QoL instrument
      and suitable for studies of osteoarthritic joint pain in the Greek setting. 

PMID- 27034833
TI  - Muscle Strength, Physical Activity, and Functional Limitations in Older Adults
      with Central Obesity.
AB  - Background. Obesity and muscle weakness are independently associated with
      increased risk of physical and functional impairment in older adults. It is
      unknown whether physical activity (PA) and muscle strength combined provide added
      protection against functional impairment. This study examines the association
      between muscle strength, PA, and functional outcomes in older adults with central
      obesity. Methods. Prevalence and odds of physical (PL), ADL, and IADL limitation
      were calculated for 6,388 community dwelling adults aged >= 60 with central
      obesity. Individuals were stratified by sex-specific hand grip tertiles and PA.
      Logistic models were adjusted for age, education, comorbidities, and body-mass
      index and weighted. Results. Overall prevalence of PL and ADL and IADL
      limitations were progressively lower by grip category. Within grip categories,
      prevalence was lower for individuals who were active than those who were
      inactive. Adjusted models showed significantly lower odds of PL OR 0.42 [0.31,
      0.56]; ADL OR 0.60 [0.43, 0.84], and IADL OR 0.46 [0.35, 0.61] for those in the
      highest grip strength category as compared to those in the lowest grip category.
      Conclusion. Improving grip strength in obese elders who are not able to engage in
      traditional exercise is important for reducing odds of physical and functional
      impairment. 

PMID- 27034834
TI  - Characterization of Jamaican Delonix regia and Cassia fistula Seed Extracts.
AB  - Delonix regia and Cassia fistula seed extracts were evaluated for their
      antioxidant activity, total phenolics, ash, zinc and fatty acid content. Fourier
      Transform Infrared Spectroscopy (FTIR) was utilized to assess the chemical
      functionalities present within the seeds. Antioxidant activity was determined by
      the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Trolox equivalent antioxidant
      capacity (TEAC) assays. Total phenolics were determined by the Folin-Ciocalteu
      assay. Lipid extracts were characterized by nuclear magnetic resonance
      spectroscopy and gas chromatography/mass spectrometry. Zinc concentration was
      determined by atomic absorption spectroscopy. Extracts from the seeds of C.
      fistula had a higher antioxidant activity, free radical scavenging activity, and
      phenolic content than D. regia. FTIR revealed that the seeds are a rich source of
      protein with small quantities of fat. C. fistula extracts contained a higher
      percentage of total fat than D. regia. Palmitic acid was identified as the
      predominant saturated fatty acid in both extracts. Oleic acid and linoleic acid
      were identified in smaller quantities. Seed extracts may be considered for use in
      food and nutraceutical applications. 

PMID- 27034835
TI  - HPV Infection and Prognostic Factors of Tongue Squamous Cell Carcinoma in
      Different Ethnic Groups from Geographically Closed Cohort in Xinjiang, China.
AB  - Background. The effect of HPV infection status and ethnic differences on the
      prognosis of tongue squamous cell carcinoma in Xinjiang presents an interesting
      set of conditions that has yet to be studied. Methods. A comprehensive analysis
      of clinical data was undertaken for a cohort consisting of 63 patients with
      tongue squamous cell carcinoma recruited from three ethnic groups in Xinjiang.
      PCR was used for the detection of HPV16 and HPV18 infections. Kaplan-Meier
      survival analysis was used for analyzing survival outcome in addition to the
      assessment of other prognostic factors. Results. The overall infection rate for
      HPV was 28.6% (18/63); the 5-year survival rate among the HPV-positive patients
      was 47.8% and 30.3% for HPV-negative patients. The survival rate for HPV-positive
      patients who received radiotherapy and chemotherapy was better than for those who
      did not receive radiotherapy and chemotherapy. N staging and HPV infection were
      found to be two independent and significant prognostic factors. Conclusion. HPV
      positive patients with tongue squamous cell carcinoma are more sensitive to
      chemotherapy. Higher N staging indicates poor prognosis. 

PMID- 27034836
TI  - An Analysis of Behaviour Change Techniques Used in a Sample of Gestational Weight
      Management Trials.
AB  - INTRODUCTION: Maternal obesity and excessive gestational weight gain are
      associated with multiple adverse outcomes. There is a lack of clarity on the
      specific components of effective interventions to support pregnant women with
      gestational weight management. METHOD: All 44 studies within a preexisting review
      of lifestyle interventions, with a potential to impact on maternal weight
      outcomes, were considered for content analysis. Interventions were classified
      using Behaviour Change Technique (BCT) taxonomy clusters to explore which
      categories of BCT were used in interventions and their effectiveness in managing
      gestational weight gain. RESULTS: The most commonly used BCTs were within the
      categories of "feedback and monitoring," "shaping knowledge," "goals and
      planning," "repetition and substitution," "antecedents," and "comparison of
      behaviours." For diet and mixed interventions "feedback and monitoring," "shaping
      knowledge," and "goals and planning" appeared the most successful BCT categories.
      CONCLUSIONS: Poor reporting within studies in defining the BCTs used, in
      clarifying the differences in processes between intervention and control groups,
      and in differentiating between the intervention and research processes made BCT
      classification difficult. Future studies should elaborate more clearly on the
      behaviour change techniques used and report them accurately to allow a better
      understanding of the effective ingredients for lifestyle interventions during
      pregnancy.

PMID- 27034837
TI  - ABPI against Colour Duplex Scan: A Screening Tool for Detection of Peripheral
      Arterial Disease in Low Resource Setting Approach to Validation.
AB  - Background. In Sri Lanka the ABPI has not been used as a screening tool to detect
      peripheral arterial disease (PAD) in epidemiological studies. This study was
      conducted to determine the best cutoff value of ABPI to detect PAD in Sri Lankan
      population. Methods. The ABPI measured by arterial Doppler to detect PAD was
      validated against colour duplex scan as the criterion using 165 individuals
      referred to vascular laboratory, National Hospital Sri Lanka. In all selected
      individuals ABPI was measured and lower limb colour duplex scan was performed.
      Narrowing of luminal diameter of lower limb arteries 50% or more was considered
      as haemodynamically significant and having PAD. The discriminative performance of
      the ABPI was assessed using Receiver Operator Characteristic (ROC) curve and
      calculating the area under the curve (AUC). The sensitivity and specificity of
      different threshold levels of ABPI and the best cutoff value of ABPI to detect
      PAD were determined. Results. ABPI 0.89 was determined as the best cutoff value
      to identify individuals with PAD. At this level of ABPI high sensitivity (87%),
      specificity (99.1%), positive predictive value (98.9%), and negative predictive
      value (88.4%) were observed. Conclusion. ABPI <= 0.89 could be used as the best
      cut off value to detect PAD. 

PMID- 27034838
TI  - Inflammatory Bowel Disease and Skin Cancer: An Assessment of Patient Risk
      Factors, Knowledge, and Skin Practices.
AB  - Objective. Patients with inflammatory bowel disease (IBD) are at increased risk
      from skin cancer. Aims include assessing IBD patients' risk factors and knowledge
      of skin cancer and current skin protection practices to identify gaps in patient
      education regarding skin cancer prevention in IBD. Methods. IBD patients >= 18
      years were recruited to complete an online survey. Results. 164 patients (mean
      age 43.5 years, 63% female) with IBD (67% Crohn's disease, 31% ulcerative
      colitis, and 2% indeterminate colitis) were included. 12% (n = 19) of patients
      had a personal history and 34% (n = 55) had a family history of skin cancer.
      Females scored better on skin protection (16.94/32 versus 14.53/32, P <= 0.03)
      and awareness (35.16/40 versus 32.98/40, P <= 0.03). Patients over 40 years old
      scored better on prevention (17.45/28 versus 15.35/28, P = 0.03). Patients with
      skin cancer scored better on prevention (20.56/28 versus 15.75/28, P <= 0.001)
      and skin protection (21.47/32 versus 15.33/32, P <= 0.001). 61% of patients
      recognized the link between skin cancer and IBD. Conclusions. The majority of IBD
      patients are aware of the link between skin cancer and IBD; however, skin
      protection practices are suboptimal. This emphasizes the role of healthcare
      professionals in providing further education for skin cancer prevention in the
      IBD population. 

PMID- 27034839
TI  - Kaposi Sarcoma among HIV Infected Patients in Lagos University Teaching Hospital,
      Nigeria: A 14-Year Retrospective Clinicopathological Study.
AB  - Background. Despite the increased incidence of Kaposi sarcoma (KS) resulting from
      the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS)
      pandemic, there is still significant underreporting of KS in this environment.
      Objectives. This study was aimed at determining the incidence and
      clinicopathologic patterns of KS among HIV infected patients in Lagos University
      Teaching Hospital (LUTH), Nigeria, over a 14-year period: January 2000 to
      December 2013. Methodology. The materials for this study included patients'
      hospital clinical files, duplicate copies of histopathologic reports, and tissue
      blocks and corresponding archival slides in the Anatomic and Molecular Pathology
      Department and the HIV/AIDS unit of the Department of Haematology. Results.
      Within the study period, 182 cases of KS were diagnosed, accounting for 1.2% of
      all patients managed for HIV/AIDS and 2.99% of solid malignant tumours. The male
      to-female ratio and modal age group were 1 : 1.3 and 5th decade, respectively.
      Most cases (90%) had purely mucocutaneous involvement with the lower limb being
      the commonest site (65.8%). The majority of lesions were plaques (65.8%).
      Vascular formation was the predominant histologic type seen (43.5%). Conclusion.
      KS in Lagos followed the same epidemiologic trend as other centers in Nigeria,
      with an increasing incidence in this era of HIV/AIDS. 

PMID- 27034840
TI  - Human T-Cell Lymphotropic Virus Types 1 and 2 Seropositivity among Blood Donors
      at Mbarara Regional Blood Bank, South Western Uganda.
AB  - Background. The human T-cell lymphotropic virus types 1 and 2 (HTLV 1/2) are
      retroviruses associated with different pathologies. HTLV-1 causes adult T-cell
      leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP); HTLV-2 is not clearly associated with a known clinical
      disease. Both viruses may be transmitted by whole blood transfusion, from mother
      to child predominantly through breastfeeding, and by sexual contact. Presently,
      none of the regional blood banks in Uganda perform routine pretransfusion
      screening for HTLV. The aim of this study was to determine the prevalence of anti
      human T-cell lymphotropic virus types 1/2 (HTLV-1/2) antibodies among blood
      donors at Mbarara Regional Blood Bank in South Western Uganda. A cross-sectional
      study was conducted between June 2014 and September 2014. Methodology.
      Consecutive blood samples of 368 blood donors were screened for anti-HTLV-1/2
      antibodies using an enzyme linked immunosorbent assay (ELISA). Samples reactive
      on a first HTLV-1/2 ELISA were further retested in duplicate using the same
      ELISA. Of the three hundred and sixty-eight blood donors (229 (62.2%) males and
      139 (37.8%) females), only two male donors aged 20 and 21 years were HTLV-1/2
      seropositive, representing a prevalence of 0.54%. Conclusion. HTLV-1/2 prevalence
      is low among blood donors at Mbarara Regional Blood Bank. Studies among other
      categories of people at risk for HTLV 1/2 infection should be carried out. 

PMID- 27034841
TI  - A Trend for Increased Risk of Revision Surgery due to Deep Infection following
      Fast-Track Hip Arthroplasty.
AB  - Rates of revision surgery due to deep infection following total hip arthroplasty
      (THA) increased at a Norwegian hospital following implementation of fast-track
      procedures. The purpose of this study was to determine whether selected
      demographic (age and sex) and clinical (body mass index, American Society of
      Anesthesiologists (ASA) classification, surgery duration, length of hospital
      stay, cemented versus uncemented prosthesis, and fast-track procedures) factors
      were associated with higher risk of revision surgery due to deep infection
      following THA. In a prospective designed study 4,406 patients undergoing primary
      THA between January 2001 and January 2013 where included. Rates of infection
      related revision surgery within 3 months of THA were higher among males and among
      patients who received fast-track THA. Adjusting for sex and age, the implemented
      fast-track elements were significantly associated with increased risk of revision
      surgery. Risk of infection-related revision surgery was unrelated to body mass
      index, physical status, surgery duration, length of hospital stay, and prosthesis
      type. Because local infiltration analgesia, drain cessation, and early
      mobilization were introduced in combination, it could not be determined which
      component or combination of components imposed the increased risk. The findings
      in this small sample raise concern about fast-track THA but require replication
      in other samples. 

PMID- 27034842
TI  - Spatiotemporal Expression and Molecular Characterization of miR-344b and miR-344c
      in the Developing Mouse Brain.
AB  - MicroRNAs (miRNAs) are small noncoding RNA known to regulate brain development.
      The expression of two novel miRNAs, namely, miR-344b and miR-344c, was
      characterized during mouse brain developmental stages in this study. In situ
      hybridization analysis showed that miR-344b and miR-344c were expressed in the
      germinal layer during embryonic brain developmental stages. In contrast, miR-344b
      was not detectable in the adult brain while miR-344c was expressed exclusively in
      the adult olfactory bulb and cerebellar granular layer. Stem-loop RT-qPCR
      analysis of whole brain RNAs showed that expression of the miR-344b and miR-344c
      was increased as brain developed throughout the embryonic stage and maintained at
      adulthood. Further investigation showed that these miRNAs were expressed in adult
      organs, where miR-344b and miR-344c were highly expressed in pancreas and brain,
      respectively. Bioinformatics analysis suggested miR-344b and miR-344c targeted
      Olig2 and Otx2 mRNAs, respectively. However, luciferase experiments demonstrated
      that these miRNAs did not target Olig2 and Otx2 mRNAs. Further investigation on
      the locality of miR-344b and miR-344c showed that both miRNAs were localized in
      nuclei of immature neurons. In conclusion, miR-344b and miR-344c were expressed
      spatiotemporally during mouse brain developmental stages. 

PMID- 27034843
TI  - Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Abeta
      Oligomers.
AB  - Increased reactive oxygen species (ROS) generation and the ensuing oxidative
      stress contribute to Alzheimer's disease pathology. We reported previously that
      amyloid-beta peptide oligomers (AbetaOs) produce aberrant Ca(2+) signals at
      sublethal concentrations and decrease the expression of type-2 ryanodine
      receptors (RyR2), which are crucial for hippocampal synaptic plasticity and
      memory. Here, we investigated whether the antioxidant agent astaxanthin (ATX)
      protects neurons from AbetaOs-induced excessive mitochondrial ROS generation,
      NFATc4 activation, and RyR2 mRNA downregulation. To determine mitochondrial H2O2
      production or NFATc4 nuclear translocation, neurons were transfected with
      plasmids coding for HyperMito or NFATc4-eGFP, respectively. Primary hippocampal
      cultures were incubated with 0.1 MUM ATX for 1.5 h prior to AbetaOs addition (500
      nM). We found that incubation with ATX (<=10 MUM) for <=24 h was nontoxic to
      neurons, evaluated by the live/dead assay. Preincubation with 0.1 MUM ATX also
      prevented the neuronal mitochondrial H2O2 generation induced within minutes of
      AbetaOs addition. Longer exposures to AbetaOs (6 h) promoted NFATc4-eGFP nuclear
      translocation and decreased RyR2 mRNA levels, evaluated by detection of the eGFP
      tagged fluorescent plasmid and qPCR, respectively. Preincubation with 0.1 MUM ATX
      prevented both effects. These results indicate that ATX protects neurons from the
      noxious effects of AbetaOs on mitochondrial ROS production, NFATc4 activation,
      and RyR2 gene expression downregulation. 

PMID- 27034844
TI  - Spindle Bursts in Neonatal Rat Cerebral Cortex.
AB  - Spontaneous and sensory evoked spindle bursts represent a functional hallmark of
      the developing cerebral cortex in vitro and in vivo. They have been observed in
      various neocortical areas of numerous species, including newborn rodents and
      preterm human infants. Spindle bursts are generated in complex neocortical
      subcortical circuits involving in many cases the participation of motor brain
      regions. Together with early gamma oscillations, spindle bursts synchronize the
      activity of a local neuronal network organized in a cortical column. Disturbances
      in spindle burst activity during corticogenesis may contribute to disorders in
      cortical architecture and in the activity-dependent control of programmed cell
      death. In this review we discuss (i) the functional properties of spindle bursts,
      (ii) the mechanisms underlying their generation, (iii) the synchronous patterns
      and cortical networks associated with spindle bursts, and (iv) the physiological
      and pathophysiological role of spindle bursts during early cortical development. 

PMID- 27034845
TI  - Stress Effects on Multiple Memory System Interactions.
AB  - Extensive behavioural, pharmacological, and neurological research reports stress
      effects on mammalian memory processes. While stress effects on memory quantity
      have been known for decades, the influence of stress on multiple memory systems
      and their distinct contributions to the learning process have only recently been
      described. In this paper, after summarizing the fundamental biological aspects of
      stress/emotional arousal and recapitulating functionally and anatomically
      distinct memory systems, we review recent animal and human studies exploring the
      effects of stress on multiple memory systems. Apart from discussing the
      interaction between distinct memory systems in stressful situations, we will also
      outline the fundamental role of the amygdala in mediating such stress effects.
      Additionally, based on the methods applied in the herein discussed studies, we
      will discuss how memory translates into behaviour. 

PMID- 27034846
TI  - Role of MicroRNA in Governing Synaptic Plasticity.
AB  - Although synaptic plasticity in neural circuits is orchestrated by an ocean of
      genes, molecules, and proteins, the underlying mechanisms remain poorly
      understood. Recently, it is well acknowledged that miRNA exerts widespread
      regulation over the translation and degradation of target gene in nervous system.
      Increasing evidence suggests that quite a few specific miRNAs play important
      roles in various respects of synaptic plasticity including synaptogenesis,
      synaptic morphology alteration, and synaptic function modification. More
      importantly, the miRNA-mediated regulation of synaptic plasticity is not only
      responsible for synapse development and function but also involved in the
      pathophysiology of plasticity-related diseases. A review is made here on the
      function of miRNAs in governing synaptic plasticity, emphasizing the emerging
      regulatory role of individual miRNAs in synaptic morphological and functional
      plasticity, as well as their implications in neurological disorders.
      Understanding of the way in which miRNAs contribute to synaptic plasticity
      provides rational clues in establishing the novel therapeutic strategy for
      plasticity-related diseases. 

PMID- 27034848
TI  - Coping with the Forced Swim Stressor: Towards Understanding an Adaptive
      Mechanism.
AB  - In the forced swim test (FST) rodents progressively show increased episodes of
      immobility if immersed in a beaker with water from where escape is not possible.
      In this test, a compound qualifies as a potential antidepressant if it prevents
      or delays the transition to this passive (energy conserving) behavioural style.
      In the past decade however the switch from active to passive "coping" was used
      increasingly to describe the phenotype of an animal that has been exposed to a
      stressful history and/or genetic modification. A PubMed analysis revealed that in
      a rapidly increasing number of papers (currently more than 2,000) stress-related
      immobility in the FST is labeled as a depression-like phenotype. In this
      contribution we will examine the different phases of information processing
      during coping with the forced swim stressor. For this purpose we focus on the
      action of corticosterone that is mediated by the closely related
      mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the limbic
      brain. The evidence available suggests a model in which we propose that the
      limbic MR-mediated response selection operates in complementary fashion with
      dopaminergic accumbens/prefrontal executive functions to regulate the transition
      between active and passive coping styles. Upon rescue from the beaker the
      preferred, mostly passive, coping style is stored in the memory via a GR
      dependent action in the hippocampal dentate gyrus. It is concluded that the
      rodent's behavioural response to a forced swim stressor does not reflect
      depression. Rather the forced swim experience provides a unique paradigm to
      investigate the mechanistic underpinning of stress coping and adaptation. 

PMID- 27034847
TI  - Chronic Stress and Glucocorticoids: From Neuronal Plasticity to
      Neurodegeneration.
AB  - Stress and stress hormones, glucocorticoids (GCs), exert widespread actions in
      central nervous system, ranging from the regulation of gene transcription,
      cellular signaling, modulation of synaptic structure, and transmission and glial
      function to behavior. Their actions are mediated by glucocorticoid and
      mineralocorticoid receptors which are nuclear receptors/transcription factors.
      While GCs primarily act to maintain homeostasis by inducing physiological and
      behavioral adaptation, prolonged exposure to stress and elevated GC levels may
      result in neuro- and psychopathology. There is now ample evidence for cause
      effect relationships between prolonged stress, elevated GC levels, and cognitive
      and mood disorders while the evidence for a link between chronic stress/GC and
      neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD)
      diseases is growing. This brief review considers some of the cellular mechanisms
      through which stress and GC may contribute to the pathogenesis of AD and PD. 

PMID- 27034849
TI  - A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging
      apoE4 Mice.
AB  - APOE epsilon4 (apoE4) polymorphism is the main genetic determinant of sporadic
      Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic
      acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid,
      vitamins B12, B6, C, and E, and selenium has been proposed for dietary management
      of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4
      mice, specifically cerebrovascular and connectivity impairment. Moreover, we
      evaluated the diet effect on cerebral blood flow (CBF), functional connectivity
      (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice.
      At 10-12 months, apoE4 mice did not display prominent pathological differences
      compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed
      reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and
      amount of synapses and improved white matter integrity and FC in both aging apoE4
      and WT mice. We demonstrated that protective mechanisms on vascular and synapse
      health are enhanced by Fortasyn, independent of apoE genotype. We further showed
      the efficacy of a multimodal translational approach, including advanced MR
      neuroimaging, to study dietary intervention on brain structure and function in
      aging. 

PMID- 27034851
TI  - Nucleolar PARP-1 Expression Is Decreased in Alzheimer's Disease: Consequences for
      Epigenetic Regulation of rDNA and Cognition.
AB  - Synaptic dysfunction is thought to play a major role in memory impairment in
      Alzheimer's disease (AD). PARP-1 has been identified as an epigenetic regulator
      of plasticity and memory. Thus, we hypothesize that PARP-1 may be altered in
      postmortem hippocampus of individuals with AD compared to age-matched controls
      without neurologic disease. We found a reduced level of PARP-1 nucleolar
      immunohistochemical staining in hippocampal pyramidal cells in AD. Nucleolar PARP
      1 staining ranged from dispersed and less intense to entirely absent in AD
      compared to the distinct nucleolar localization in hippocampal pyramidal neurons
      in controls. In cases of AD, the percentage of hippocampal pyramidal cells with
      nucleoli that were positive for both PARP-1 and the nucleolar marker fibrillarin
      was significantly lower than in controls. PARP-1 nucleolar expression emerges as
      a sensitive marker of functional changes in AD and suggests a novel role for PARP
      1 dysregulation in AD pathology. 

PMID- 27034852
TI  - Neoatherosclerosis in Very Late Stenosis of Bare Metal Stent by Optical Coherence
      Tomography.
AB  - Bare metal stents (BMS) continue to be widely used in patients with coronary
      artery disease undergoing percutaneous revascularization. Progressive luminal
      renarrowing has been reported late after BMS implantation resulting in a
      significant rate of stent failure events. We present a case of very late BMS
      failure due to in-stent restenosis where optical coherence tomography (OCT) was
      used to demonstrate neoatherosclerosis as the underlying mechanism. We provide a
      brief review of neoatherosclerosis and showcase salient features on OCT
      evaluation. 

PMID- 27034853
TI  - Chest Pain: The Need to Consider Less Frequent Diagnosis.
AB  - Chest pain is one of the most frequent patient's complaints. The commonest
      underlying causes are well known, but, sometimes, in some clinical scenarios, it
      is necessary to consider other diagnoses. We report a case of a 68-year-old
      Caucasian male, chronically hypertensive, who complained of recurrent episodes of
      chest pain and fever with elevated acute phase reactants. The first investigation
      was negative for some of the most likely diagnosis and he quickly improved with
      anti-inflammatory drugs. Over a few months, his symptoms continued to recur
      periodically, his hypertension was aggravated, and he developed headaches and
      lower limbs claudication. After a temporal artery biopsy that was negative for
      vasculitis, he underwent a positron emission tomography suggestive of Takayasu
      Arteritis. Takayasu Arteritis is a rare chronic granulomatous vasculitis of the
      aorta and its first-order branches affecting mostly females up to 50 years old.
      Chest pain is experienced by >40% of the patients and results from the
      inflammation of the aorta, pulmonary artery, or coronaries. 

PMID- 27034850
TI  - Spindle Oscillations in Sleep Disorders: A Systematic Review.
AB  - Measurement of sleep microarchitecture and neural oscillations is an increasingly
      popular technique for quantifying EEG sleep activity. Many studies have examined
      sleep spindle oscillations in sleep-disordered adults; however reviews of this
      literature are scarce. As such, our overarching aim was to critically review
      experimental studies examining sleep spindle activity between adults with and
      without different sleep disorders. Articles were obtained using a systematic
      methodology with a priori criteria. Thirty-seven studies meeting final inclusion
      criteria were reviewed, with studies grouped across three categories: insomnia,
      hypersomnias, and sleep-related movement disorders (including parasomnias).
      Studies of patients with insomnia and sleep-disordered breathing were more
      abundant relative to other diagnoses. All studies were cross-sectional. Studies
      were largely inconsistent regarding spindle activity differences between clinical
      and nonclinical groups, with some reporting greater or less activity, while many
      others reported no group differences. Stark inconsistencies in sample
      characteristics (e.g., age range and diagnostic criteria) and methods of analysis
      (e.g., spindle bandwidth selection, visual detection versus digital filtering,
      absolute versus relative spectral power, and NREM2 versus NREM3) suggest a need
      for greater use of event-based detection methods and increased research
      standardization. Hypotheses regarding the clinical and empirical implications of
      these findings, and suggestions for potential future studies, are also discussed.

PMID- 27034854
TI  - Gingival Enlargement Induced by Felodipine Resolves with a Conventional
      Periodontal Treatment and Drug Modification.
AB  - We present a case of a 47-year-old male who suffered from GE around his lower
      anterior teeth as soon as he started treatment with Felodipine 400 mg. We show
      that oral hygiene measures, antibiotics, and conventional periodontal treatment
      (scaling and root planing SRP) were all not sufficient to resolve the drug
      induced GE, which will persist and/or recur provided that systemic effect of the
      offending medication is still present. The condition immediately resolved after
      switching to a different medication. The mechanism of GE is complex and not fully
      understood yet. It is mainly due to overexpression of a number of growth factors
      due to high concentrations of calcium ions (Ca(2+)). This affects fibroblasts
      proliferation and DNA synthesis and leads to a heavy chronic inflammatory cell
      infiltrate. Our case was managed according to the suggested protocols in previous
      case studies. The unique features in our case were the immediate onset of the
      adverse effect after starting the medication and the absence of any underlying
      medical condition apart from high blood pressure. Improving the oral hygiene
      together with SRP and cessation of the medication resolves drug induced GE. 

PMID- 27034855
TI  - Treatment of Class II Division 2 Malocclusion Using the Forsus Fatigue Resistance
      Device and 5-Year Follow-Up.
AB  - This case report presents the treatment of a 14-year-and-8-month-old boy with
      Class II division 2 mandibular retrusion, severe deep bite, and concave profile.
      The Forsus fatigue resistance device (FRD) was effective in correcting both
      skeletal and dental parameters. At 5-year posttreatment follow-up, the teeth were
      well aligned and the occlusion was stable. FRD application with appropriate
      treatment time can result with prominent changes in the facial profile and
      dentition, and the outcomes can be maintained at the long-term follow-up periods.

PMID- 27034856
TI  - A Case Report of Dramatically Increased Thyroglobulin after Lymph Node Biopsy in
      Thyroid Carcinoma after Total Thyroidectomy and Radioiodine.
AB  - Thyroglobulin (Tg) is an important modality for monitoring patients with thyroid
      cancers, especially after thyroidectomy followed by radioiodine (RAI). It is also
      used as a marker for burden of thyroid tissue whether malignant or benign.
      Although there have been several reports of rising serum Tg transiently after
      thyroid biopsy in intact glands and following palpation or trauma, there are no
      reports in the literature of elevation in Tg after biopsy of suspicious lesions
      in thyroidectomized patients. In this paper we report a fascinating case of a
      considerable and initially worrying, although ultimately transient, rise in Tg in
      a patient 2 years after total thyroidectomy and RAI ablation after fine needle
      aspiration (FNA) of a suspicious thyroid bed nodule that was proven positive. 

PMID- 27034857
TI  - Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different
      Responses to Chemotherapy.
AB  - We report a case of acute myeloid leukemia (AML) with two cytogenetically
      unrelated clones. The patient was a 45-year-old male who was diagnosed with acute
      monoblastic leukemia (AMoL). Initial G-band analysis showed
      51,XY,+6,+8,inv(9)(p12q13)c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis
      after induction therapy showed 45,XY,
      7,inv(9)(p12q13)c[19]/46,XY,inv(9)(p12q13)c[1]. Retrospective FISH analysis
      revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with
      multiple trisomies was eliminated after induction therapy and never recurred, but
      a clone with monosomy 7 was still detected in myelodysplastic marrow with a
      normal blast percentage. Both clones were successfully eliminated after related
      peripheral blood stem cell transplantation, but the patient died of relapsed AML
      with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6,
      8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with
      myelodysplasia-related changes(AML-MRC) with chromosome 7 monosomy showing
      different responses to chemotherapy. Simultaneous onset of cytogenetically
      unrelated hematological malignancies that each have a different disease status is
      a rare phenomenon but is important to diagnose for a correct understanding of the
      disease status and for establishing an appropriate treatment strategy. 

PMID- 27034858
TI  - Erythrocytosis due to PHD2 Mutations: A Review of Clinical Presentation,
      Diagnosis, and Genetics.
AB  - The association of mutations in the PHD2 protein of the hypoxia-sensing pathway
      and erythrocytosis has only been established in the last decade. Here we report
      the case of a novel PHD2 gene mutation in a patient with erythrocytosis and
      summarize all reported cases to date. Case Report. A 55-year-old man presented
      with dyspnea and a previous diagnosis of idiopathic erythrocytosis. PHD gene
      sequencing revealed a mutation on exon 2. The mutation was recognized as
      p.(Trp334(*)) (c. 1001G>A) resulting in a truncation of a highly conserved amino
      acid residue in catalytic domain. A diagnosis of erythrocytosis secondary to
      mutant PHD2 gene was made. Conclusions. Our findings indicate that with PHD2
      mutations there is moderate erythrocytosis and erythropoietin (Epo) levels are
      generally low to normal. Two patients with PHD2 substitution mutations were found
      to have paraganglioma and one of these patients had a concurrent
      pheochromocytoma. In addition, one mutation was associated with sagittal sinus
      thrombosis. Given the severity of some of the clinical features of these
      mutations, we conclude that clinical guidelines should include the PHD2 mutation
      in the idiopathic erythrocytosis workup. 

PMID- 27034859
TI  - Tuberculosis of the Breast: An Initial Presentation of the Metabolic Syndrome
      with Type 2 Diabetes Mellitus in a Young Nigerian Woman.
AB  - Breast tuberculosis is an uncommon presentation of extra pulmonary tuberculosis.
      A 40-year-old obese woman presented with a right breast abscess which had failed
      to heal after surgical drainage. There was no family history of breast disease.
      Biopsy and histology of the lesion showed chronic granulomatous inflammation with
      positive stains for acid fast bacilli compatible with tuberculosis. Further
      evaluation confirmed metabolic syndrome with type 2 diabetes mellitus. She was
      placed on antituberculosis chemotherapy and appropriate therapy for diabetes
      mellitus with complete resolution of the lesion. We report this case because of
      its rarity and to highlight the association between tuberculosis an infectious
      disease and overnutrition in diabetes mellitus, a noncommunicable disease. 

PMID- 27034860
TI  - A Case of Primary Hypoparathyroidism Presenting with Acute Kidney Injury
      Secondary to Rhabdomyolysis.
AB  - Hypoparathyroidism is the most common cause of symmetric calcification of the
      basal ganglia. Herein, a case of primary hypoparathyroidism with severe tetany,
      rhabdomyolysis, and acute kidney injury is presented. A 26-year-old male was
      admitted to the emergency clinic with leg pain and cramps, nausea, vomiting, and
      decreased amount of urine. He had been treated for epilepsy for the last 10
      years. He was admitted to the emergency department for leg pain, cramping in the
      hands and legs, and agitation multiple times within the last six months. He was
      prescribed antidepressant and antipsychotic medications. He had a blood pressure
      of 150/90 mmHg, diffuse abdominal tenderness, and abdominal muscle rigidity on
      physical examination. Pathological laboratory findings were as follows:
      creatinine, 7.5 mg/dL, calcium, 3.7 mg/dL, alanine transaminase, 4349 U/L,
      aspartate transaminase, 5237 U/L, creatine phosphokinase, 262.000 U/L, and
      parathyroid hormone, 0 pg/mL. There were bilateral symmetrical calcifications in
      basal ganglia and the cerebellum on computerized tomography. He was diagnosed as
      primary hypoparathyroidism and acute kidney injury secondary to severe
      rhabdomyolysis. Brain calcifications, although rare, should be considered in
      dealing with patients with neurological symptoms, symmetrical cranial
      calcifications, and calcium metabolism abnormalities. 

PMID- 27034861
TI  - Resin-Induced Colonic Pseudotumor: Rare Complication from Chronic Use of
      Potassium Binders in a Hemodialysis Patient.
AB  - Potassium-binding resins are widely used in the treatment of hyperkalemia, mostly
      in the acute setting. Gastrointestinal adverse events, although reported, are not
      frequently seen due to its short course of use. This report describes a case
      involving an end-stage renal disease patient on hemodialysis who developed a
      colonic mass after being on sodium polystyrene sulfonate chronically for
      persistent hyperkalemia. Gastrointestinal symptoms developed late during the
      treatment rather than early as reported previously in the literature. This mass
      was mistaken for a carcinomatous lesion, which initiated an extensive work-up as
      well as hospitalization that nearly resulted in a subtotal colectomy. 

PMID- 27034862
TI  - Spontaneous Rupture of an Ovarian Artery Aneurysm: A Rare Postpartum
      Complication.
AB  - Background. Spontaneous rupture of an ovarian artery aneurysm is a rare but
      usually life-threatening event. It is most often associated with pregnancy or
      fibroids. Our case followed a normal vaginal delivery and then a delayed
      presentation with features similar to other less life-threatening postpartum
      conditions. The diagnosis could have been missed but for the meticulous and
      timely interventions which avoided catastrophic outcome. Case. This is a case of
      a multiparous woman with rupture of a left ovarian artery aneurysm, causing
      massive retroperitoneal hemorrhage and hematoma that required a combination of
      arterial embolization, percutaneous CT scan guided drainage, and surgical
      evacuation of the hematoma. Conclusion. Spontaneous rupture of ovarian artery
      should be considered as one of the differential diagnoses in the immediate
      postpartum period especially when the clinical symptoms do not correlate with the
      amount of blood loss. A high index of suspicion, prompt diagnosis, intervention,
      and a multidisciplinary approach in the management were the elements of a
      successful outcome in this case. 

PMID- 27034863
TI  - Torsion of a Subserosal Myoma Managed by Gasless Laparoendoscopic Single-Site
      Myomectomy with In-Bag Manual Extraction.
AB  - Acute torsion of a subserosal myoma is a rare surgical emergency that is
      infrequently diagnosed preoperatively. Furthermore, laparoendoscopic single-site
      (LESS) myomectomy with in-bag tissue extraction for the management of this
      disorder has not yet been described. A 43-year-old, gravida 1, para 1 woman was
      referred to our department due to a solid pelvic mass associated with persistent
      abdominal pain. A pedunculated subserosal myoma with torsion was strongly
      suspected based on ultrasonography and magnetic resonance imaging. Emergency LESS
      surgery showed that the subserosal myoma arising from the posterior uterine wall
      torted at its pedicle in the cul-de-sac. The twisted myoma node was excised by
      coagulation and cut using a LigaSure Atlas, followed by in-bag manual
      morcellation and extraction through an umbilical wound. The present case report
      emphasizes that LESS myomectomy with in-bag tissue extraction is a feasible
      minimally invasive surgical option for the management of subserosal myoma with
      torsion after a precise imaging-based diagnostic evaluation. 

PMID- 27034864
TI  - Unusual Presentation of Hypothyroidism in a Pregnant Woman, Mimicking Gestational
      Trophoblastic Neoplasm.
AB  - Hypothyroidism is a common health issue worldwide with varying clinical
      manifestations. We report a woman who experienced an incomplete abortion and
      undiagnosed hypothyroidism who was referred to the oncologist with the suspicion
      of metastatic gestational trophoblastic neoplasm (GTN). A 29-year-old woman with
      incomplete abortion was referred to an oncologist for possible GTN due to
      persistent active vaginal bleeding, an elevated beta human chorionic gonadotropin
      (hCG), abnormal cervical inspection exam, abnormal liver function tests, ovarian
      enlargement, ascites, and a pleural effusion. She was found to have
      hypothyroidism in further work-up. She was managed with thyroid hormone
      replacement therapy and her condition improved after 6 weeks. Complete resolution
      of the ovarian mass and pericardial and pleural effusion was achieved. This case
      describes an important experience; hypothyroidism should be considered in the
      differential diagnosis of any woman with an incomplete abortion presenting with
      an ovarian mass. Evaluation and correct diagnosis are important to prevent
      mismanagement. 

PMID- 27034865
TI  - Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report.
AB  - Metastatic tumours of pleura are the most common malignant tumours causing
      malignant pleural effusion. Lungs are the most common primary sites. Primary
      pleural tumours are rarely seen and diffuse malignant mesothelioma is the most
      common malignant tumour of pleura. Primary malignant neuroendocrine tumour of
      pleura is not reported in the literature. Here, we report a rare case of primary
      malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker
      female who presented with right-sided pleural effusion and ipsilateral, dull
      aching chest pain. Clinical presentations of inflammatory lesions like
      tuberculous pleuritis and benign and malignant neoplasms of pleura are
      indistinguishable; hence, fluid cytology, pleural biopsy, and
      immunohistochemistry are necessary for exact tissue diagnosis of the tumours,
      which is mandatory for correct treatment and prognostic assessment. 

PMID- 27034866
TI  - A 27-Year-Old Patient Fulfilling the Diagnostic Criteria of Both CMML and JMML.
AB  - Chronic myelomonocytic leukaemia (CMML) and juvenile myelomonocytic leukaemia
      (JMML) are two disease entities that come under the
      myelodysplastic/myeloproliferative neoplasms category. Each of the two conditions
      has its own diagnostic criteria. In addition, they have different ages of
      presentation; while CMML is typically a disease of the elderly, JMML is a disease
      of young children. Here we are presenting the case of a 27-year-old male patient
      who, at the time of diagnosis, fulfilled the diagnostic criteria of both
      diseases. In addition he had radiological changes of type 1 neurofibromatosis.
      Possible explanations of the patient case have been discussed. 

PMID- 27034867
TI  - Laparoscopic Resection of Recurrence from Hepatocellular Carcinoma after Liver
      Transplantation: Case Reports and Review of the Literature.
AB  - Background. Recurrence of hepatocellular carcinoma (HCC) after liver
      transplantation (LT) indicates a poor prognosis. Surgery is considered the only
      curative option for selected patients with HCC recurrence following LT.
      Traditionally, the preference is given to the open approach. Methods. In this
      report, we present two cases of laparoscopic resections (LR) for recurrent HCC
      after LT, performed at Oslo University Hospital, Rikshospitalet. Results. Both
      procedures were executed without intraoperative and postoperative adverse events.
      Whereas one of the patients had a recurrence one year after LR, the other patient
      did not have any sign of disease during 3-year follow-up. Conclusions. We argue
      that, in selected cases, patients with HCC recurrence following LT may benefit
      from LR due to its limited tissue trauma and timely start of subsequent treatment
      if curative resection cannot be obtained. In patients with relatively favorable
      prognosis, LR facilitates postoperative recovery course and avoids unnecessary
      laparotomy. 

PMID- 27034868
TI  - Plasmablastic Lymphoma Mimicking Acute Pancreatitis.
AB  - Background. Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm. It
      predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)
      positive patients and exhibits a highly aggressive clinical behavior. Case
      Presentation. We describe an unusual case of a 37-year-old HIV-positive male who
      presented with acute pancreatitis secondary to multiple peripancreatic masses
      compressing the pancreas. Histopathological examination of the lesions showed
      diffuse and cohesive pattern of large B-cells resembling immunoblasts or
      plasmablasts. The neoplastic cells were positive for BOB1 and MUM1, partially
      positive for CD79a, and negative for CD20, CD56, CD138, CD3, CD5, AE1/AE3, and
      HHV8. Epstein-Barr virus-encoded RNA in situ hybridization was positive. These
      features were consistent with PBL. The patient was initiated on cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, demonstrating a
      striking response. Conclusion. To our research, this is the first report of PBL
      with the initial presentation of acute pancreatitis. The findings in this case
      suggest that PBL should be included in the differential diagnosis of pancreatic
      and peripancreatic tumors. 

PMID- 27034869
TI  - Postoperative Nocardia Endophthalmitis and the Challenge of Managing with
      Intravitreal Amikacin.
AB  - Nocardia is a rare cause of delayed onset postoperative endophthalmitis after
      cataract surgery and it usually carries a guarded visual prognosis. Purpose. To
      highlight the clinical presentation, microbiological profile, and treatment
      outcome in a case of nocardial endophthalmitis after manual small incision
      cataract surgery. Methods. This case report highlights the typical features of
      Nocardia endophthalmitis, which presented six weeks after undergoing small
      incision cataract surgery. The case was managed by pars plana vitrectomy with
      intravitreal antibiotics. Intravitreal amikacin was used based on microbiologic
      work-up. Results. The endophthalmitis part was controlled but the case developed
      amikacin induced macular infarction which jeopardized a good visual outcome.
      Conclusion. Nocardia endophthalmitis manifests late after cataract surgery in an
      aggressive manner and carries a poor visual prognosis. An early diagnosis and the
      use of correct antibiotic regimen may salvage the vision. But the present case
      shows that one should always be wary of potential retinal toxicity with
      intravitreal amikacin. 

PMID- 27034870
TI  - Cervical Spondylotic Myelopathy Secondary to Dropped Head Syndrome: Report of a
      Case and Review of the Literature.
AB  - The dropped head syndrome (DHS) is a disabling condition caused by severe
      weakness of the neck extensor muscles causing progressive reducible kyphosis of
      the cervical spine and the inability to hold the head up. Weakness can occur in
      isolation or in association with a generalized neuromuscular disorder. Isolated
      cases are owed to the late onset of noninflammatory myopathy designated as INEM,
      where persistent chin to chest deformity may gradually cause or aggravate
      preexisting degenerative changes of the cervical spine and ultimately result in
      myelopathy. In review of the literature, we could find only 5 cases, with no
      unique guidelines to address the management of these two concomitant pathologies.
      Herein, a 69-year-old man who had developed cervical myelopathy 2 years after
      being affected by isolated dropped head syndrome is presented. Chin to chest
      deformity and cervical myelopathy were managed through three-level anterior
      cervical discectomy and fusion (ACDF) combined with decompressive cervical
      laminectomy and stabilization with C2 to C7 pedicle screw-rod construct. At 4
      month follow-up, despite recovery in patient's neurological status, flexion
      deformity reappeared with recurrence of dropped head due to C7 pedicle screws
      pull-out. However, this was successfully managed with extension of the construct
      to the upper thoracic levels. 

PMID- 27034871
TI  - Salmonella Typhi Vertebral Osteomyelitis and Epidural Abscess.
AB  - Salmonella vertebral osteomyelitis is an uncommon complication of Salmonella
      infection. We report a case of a 57-year-old transgender male who presented with
      lower back pain for a period of one month following a fall. Physical examination
      only revealed tenderness over the lower back with no neurological deficits. MRI
      of the thoracic and lumbar spine revealed a spondylodiscitis at T10-T11 and T12
      L1 and right posterior epidural collection at the T9-T10 level. He underwent
      decompression laminectomy with segmental instrumentation and fusion of T8 to L3
      vertebrae. Intraoperatively, he was found to have acute-on-chronic osteomyelitis
      in T10 and T11, epidural abscess, and discitis in T12-L1. Tissue and wound
      culture grew Salmonella Typhi and with antibiotics susceptibility guidance he was
      treated with intravenous ceftriaxone for a period of six weeks. He recovered well
      with no neurological deficits. 

PMID- 27034872
TI  - Voluminous Myoepithelioma of the Minor Salivary Glands Involving the Base of the
      Tongue.
AB  - Myoepithelioma is an extremely rare tumour subtype and diagnosis is based on a
      wide variation of cellular morphology. FNAC specimens do not always suffice for a
      definitive differential diagnosis which depends on histology and
      immunohistochemistry of the lesion. Case Presentation. A 54-year-old female came
      to our attention with dysphagia and dyslalia of 6-month standing. Ear, Nose, and
      Throat (ENT) examination revealed a voluminous mass on the right portion of the
      base of her tongue, where postcontrast T2-weighted Magnetic Resonance Imaging
      (MRI) evidenced a hyperintense lesion. The fine-needle aspiration specimen taken
      for cytology was not diagnostic, as a differential diagnosis between
      myoepithelioma and a malignant neoplasm of the salivary glands necessitates
      parameters that cytology alone cannot provide. Therefore, the whole lesion was
      excised by diode laser through a transoral approach. Histology and
      immunohistochemistry of the completely excised lesion confirmed a myoepithelioma.

PMID- 27034873
TI  - Surgical Approaches to First Branchial Cleft Anomaly Excision: A Case Series.
AB  - Objectives. First branchial cleft anomalies (BCAs) constitute a rare entity with
      variable clinical presentations and anatomic findings. Given the high rate of
      recurrence with incomplete excision, identification of the entire tract during
      surgical treatment is of paramount importance. The objectives of this paper were
      to present five anatomic variations of first BCAs and describe the presentation,
      evaluation, and surgical approach to each one. Methods. A retrospective case
      review and literature review were performed. We describe patient characteristics,
      presentation, evaluation, and surgical approach of five patients with first BCAs.
      Results. Age at definitive surgical treatment ranged from 8 months to 7 years.
      Various clinical presentations were encountered, some of which were atypical for
      first BCAs. All had preoperative imaging demonstrating the tract. Four surgical
      approaches required a superficial parotidectomy with identification of the facial
      nerve, one of which revealed an aberrant facial nerve. In one case the tract was
      found to travel into the angle of the mandible, terminating as a mandibular cyst.
      This required en bloc excision that included the lateral cortex of the mandible.
      Conclusions. First BCAs have variable presentations. Complete surgical excision
      can be challenging. Therefore, careful preoperative planning and the recognition
      of atypical variants during surgery are essential. 

PMID- 27034874
TI  - Transient Creatine Kinase Elevation Followed by Hypocomplementemia in a Case of
      Rotavirus Myositis.
AB  - We report an infant case of rotavirus myositis, a rare complication of rotavirus
      infection. Complement levels of the patient were normal when serum creatine
      kinase (CK) level was at its peak and then decreased when the CK level became
      normalized. In a previous case report of rotavirus myositis, transient decrease
      of serum albumin, immunoglobulin, and complement levels was reported. The authors
      speculated that intravascular complement activation was caused by rotavirus and
      resulted in the pathogenesis of myositis, although complement levels at onset
      were not measured by the authors. In this report, however, we demonstrate that
      the complement activation of our patient is a result of, rather than the cause
      of, skeletal muscle damage. 

PMID- 27034875
TI  - Quetiapine-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone.
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can be
      induced by various conditions, including malignant neoplasms, infections, central
      nervous system disorders, and numerous drugs. We here report a case of a 65-year
      old female patient, treated with quetiapine for schizophrenia, who presented with
      generalized tonic-clonic seizures and was finally diagnosed with quetiapine
      induced SIADH. Quetiapine-associated hyponatremia is extremely uncommon and only
      a few, relevant reports can be found in the literature. This case underlines the
      fact that patients on antipsychotic medication and more specifically on
      quetiapine should be closely monitored and routinely tested for electrolyte
      disorders. 

PMID- 27034876
TI  - Cholangiocarcinoma Arising from a Type VI Biliary Cyst: A Case Report and Review
      of the Literature.
AB  - Cystic dilatations of the cystic duct which are suggested as type VI biliary
      cysts are very rare and many of them go unrecognized or are confused with other
      cysts until the operation although they are obvious on imaging studies. They can
      present with fusiform or saccular dilatations and can be accompanied by common
      bile duct dilatations. It is important to identify these cysts as they share the
      same characteristics as the other biliary cyst types and can be complicated with
      malignancy. We herein present a very unusual case of a cholangiocarcinoma arising
      from a type VI biliary cyst in a 58-year-old female patient and review the
      literature. The patient presented with jaundice, weight loss, and abdominal pain.
      On imaging, the cystic duct and common bile duct were fusiformly dilated and had
      a wide communication. There was a mass filling the distal parts of both ducts.
      The patient was urgently operated on after perforation following ERCP.
      Histopathology was compatible with a type VI biliary cyst and an associated
      cholangiocarcinoma. 

PMID- 27034877
TI  - Hypoxemia and Right-to-Left-Shunt in Patient with Antiphospholipid Syndrome: A
      Case Report with Multimodality Imaging Findings and Literature Review.
AB  - This is a case report of an extremely rare cause of superior vena cava syndrome
      with systemic-to-pulmonary venous shunts, illustrated using different imaging
      modalities with successful SVC and IVC dilatation and stenting. 

PMID- 27034878
TI  - Multiple Brain Abscesses due to Streptococcus anginosus: Prediction of Mortality
      by an Imaging Severity Index Score.
AB  - An elderly patient with altered mental status, brain abscesses, ventriculitis,
      and empyemas died of septic shock and brain abscesses secondary to Streptococcus
      anginosus despite aggressive treatment. An imaging severity index score with a
      better prognostic value than the Glasgow coma scale predicted mortality in this
      patient. 

PMID- 27034879
TI  - Successful Discontinuation of Infliximab in a Refractory Case of Vasculo-Behcet
      Disease.
AB  - Reports have shown that antitumor necrosis factor alpha (anti-TNF-alpha) agents
      including infliximab (IFX) can dramatically suppress the disease activity of
      refractory vasculo-Behcet disease (vasculo-BD). However, it is completely unknown
      whether we can discontinue anti-TNF-alpha agents under clinical remission. A 31
      year-old patient with vasculo-BD was initially treated with a high dose of
      steroid and intravenous cyclophosphamide therapy. Six months later, however, the
      disease recurred. IFX was administered and immediately the disease activity was
      reduced. Fortunately, we could discontinue IFX after 18-month remission and no
      recurrence has been observed. Based on previous reports and our patient, all
      patients who could discontinue IFX sustained clinical remission for at least one
      year, continued taking immunosuppressive agents such as methotrexate and
      azathioprine, and had vascular involvements only in non-life-threatening major
      vessels such as leg or arm arteries/veins. This is a report suggesting the
      possibility of discontinuation of IFX in vasculo-BD. 

PMID- 27034880
TI  - Pancreatic Aetiology for Massive Upper Gastrointestinal Haemorrhage in Pregnancy.
AB  - We present herein what we believe is the first reported case of massive upper
      gastrointestinal bleeding in pregnancy due to a pancreatic neuroendocrine tumour
      causing left sided portal hypertension. A 37-year-old 27-week pregnant female
      presented with massive haematemesis and melaena requiring transfusion of 10 units
      of red cell concentrate. Gastric varices were evident at endoscopy. An MRI
      revealed a large mass infiltrating the pancreatic tail and spleen with massive
      upper abdominal varix formation secondary to splenic vein invasion. A caesarean
      section was performed, followed by a radical en bloc partial pancreatectomy and
      splenectomy with resection of the fundus of the stomach and ligation of gastric
      and splenic varices. Her postoperative course was uncomplicated. Histology
      revealed a well differentiated grade 2 neuroendocrine tumour with final staging
      of T4N0. This case highlights an infrequently encountered cause of massive
      gastrointestinal bleeding. Diagnosis and management of pancreatic neuroendocrine
      tumours, due to their rarity and variable clinical presentation, can be
      challenging particularly in the setting of pregnancy where the wellbeing of a
      second patient must also be considered. A multidisciplinary approach with input
      from obstetricians and general surgeons is required when deciding optimum
      management, while also taking into account the patient's preferences. 

PMID- 27034881
TI  - A Case of Laparoscopic Resection for Carcinoma of the Gastric Remnant following
      Proximal Gastrectomy Reconstructed with Jejunal Interposition.
AB  - A 72-year-old Japanese man had a history of proximal gastrectomy for early
      gastric cancer located in the upper third of the stomach in 2007. Our usual
      treatment strategy for early gastric cancer in the upper third of the stomach in
      2007 was open proximal gastrectomy reconstructing by jejunal interposition with a
      10 cm single loop. Upper gastrointestinal fiberscopy for annual follow-up
      revealed a type 0-IIc-shaped tumor with ulcer scar, 4.0 cm in size, located in
      the gastric remnant near the jejunogastrostomy. A clinical diagnosis of cancer of
      the gastric remnant, clinical T1b(SM)N0M0, Stage IA, following the proximal
      gastrectomy was made and a laparoscopic approach was selected because of the
      cancer's early stage. Remnant total gastrectomy with D1 plus lymphadenectomy was
      carried out with five ports by a pneumoperitoneal method. Complete resection of
      the reconstructed jejunum was undergone along with the jejunal mesentery.
      Reconstruction by the Roux-en-Y method via the antecolic route was selected.
      Total operative time was 395 min and blood loss was 40 mL. Our patient was the
      first successful case of resection for carcinoma of the gastric remnant following
      proximal gastrectomy reconstructed with jejunal interposition in a laparoscopic
      approach. 

PMID- 27034882
TI  - Seminoma in a Man with Russell-Silver Syndrome Presenting with Testicular
      Torsion.
AB  - Russell-Silver syndrome (RSS) is a type of primordial dwarfism. Only one case of
      testicular cancer in RSS has been reported, the pathology of which was
      nonseminoma. Here, we report a case of seminoma in a 36-year-old man who was
      diagnosed with RSS at birth. The seminoma was diagnosed when the patient
      presented with testicular torsion. This is the first report of testicular
      seminoma in an RSS patient in the literature. We also discussed the correlation
      between seminoma and RSS. 

PMID- 27034883
TI  - Granulomatosis with Polyangiitis (Wegener's Granulomatosis) Accompanied by
      Dysuria.
AB  - A 65-year-old male visited us with complaints of retarded urination, dysuria,
      gross hematuria, and fever. Urinalysis showed pyuria. Prostatic tumor with lung
      metastasis was suspected from computed tomography and magnetic resonance imaging.
      Transurethral prostatic biopsy and bronchoscopic biopsy only revealed fibrinoid
      necrosis and inflammatory infiltration. Right lateral maxillary sinusitis was
      also found by MRI. ANCA testing was positive with specificity for anti-PR3 (PR3
      ANCA). On the basis of these results, Granulomatosis with polyangiitis (GPA) was
      diagnosed. GPA involving the prostate gland is unusual, and only a few cases have
      previously been reported. 

PMID- 27034884
TI  - Depression and Anxiety following Coronary Artery Bypass Graft: Current Indian
      Scenario.
AB  - Epidemiological studies have shown a high prevalence of coronary artery disease
      among the Indian Population. Due to increasing availability and affordability of
      tertiary care in many parts of India, carefully selected patients undergo
      coronary artery bypass surgery to improve cardiac function. However, the
      procedure is commonly associated with depression and anxiety which can adversely
      affect overall prognosis. The objective of this review is to highlight early
      identifiable symptoms of depression and anxiety following coronary artery bypass
      graft (CABG) in Indian context so as to facilitate prompt intervention for better
      outcome. The current review was able to establish firm evidence in support of
      screening for depression and anxiety following CABG. Management of depression and
      anxiety following CABG is briefly reviewed. 

PMID- 27034885
TI  - Significance of Interleukin-6 in Papillary Thyroid Carcinoma.
AB  - This study sought to reveal the significance of IL-6 in papillary thyroid
      carcinoma by determining its circulating levels, tumoral protein, and mRNA
      expressions. As compared to the healthy individuals, serum IL-6 was significantly
      higher in patients with benign thyroid diseases and PTC. Further, its level was
      significantly higher in PTC patients as compared to patients with benign thyroid
      diseases. ROC curves also confirmed a good discriminatory efficacy of serum IL-6
      between healthy individuals and patients with benign thyroid diseases and PTC.
      The circulating IL-6 was significantly associated with poor overall survival in
      PTC patients. IL-6 immunoreactivity was significantly high in PTC patients as
      compared to the benign thyroid disease patients. Significantly higher IL-6 mRNA
      expression was also observed in the primary tumour tissues of PTC patients than
      the adjacent normal tissues. The protein expression of IL-6 at both the
      circulating and tissue level correlated with disease aggressiveness in PTC
      patients. Moreover, a significant positive correlation was observed between the
      IL-6 protein and mRNA expression in the primary tumours of PTC patients. Finally
      in conclusion, IL-6 has an important role in thyroid cancer progression. Thus
      targeting IL-6 signalling can help in clinical management of thyroid carcinoma
      patients. 

PMID- 27034886
TI  - Effect of Preoperative Nerve Block on Postthyroidectomy Headache and Cervical
      Pain: A Randomized Prospective Study.
AB  - The aim of the current study was to investigate the efficacy of greater occipital
      nerve (GON) block and bilateral superficial cervical plexuses (BSCP) blocks in
      alleviating postoperative occipital headache and posterior neck pain after
      thyroidectomy. This randomized prospective study consisted of 75 women undergoing
      total thyroidectomy. Patients were randomized into three groups: Group I (n =
      25): patients receiving GON, Group II (n = 25): patients receiving bilateral
      (BSCP) blocks, and Group III (n = 25): patients receiving no block. Assessment of
      occipital headache, posterior neck, and incision site pains was made at 12 hours
      and 24 hours after extubation by Visual Analogue Scale (VAS). In comparison to
      Group III significantly fewer patients in Groups I and II experienced occipital
      headache at 12 (p = 0.006) and 24 hours (p = 0.005) and also posterior neck pain
      at 24 hours (p = 0.003). Mean VAS scores at 12 and 24 hours for occipital
      headache (p = 0.003 and p = 0.041) and posterior neck pain (p = 0.015 and p =
      0.008) were significantly lower in Group I. The differences between Groups II and
      III were not significant except for the occipital headache at 12 hours. The
      efficacy of GON block is superior to BSCP blocks in alleviating postthyroidectomy
      occipital headache and posterior cervical pain. 

PMID- 27034887
TI  - Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in
      Parkin-Mutant Fibroblasts from Parkinson's Disease Patients.
AB  - Mutations in the parkin gene are the most common cause of early-onset Parkinson's
      disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain
      function, mitophagy, and mitochondrial dynamics. Human cellular models with
      parkin null mutations are particularly valuable for investigating the
      mitochondrial functions of parkin. However, published results reporting on
      patient-derived parkin-mutant fibroblasts have been inconsistent. This study
      aimed to functionally compare parkin-mutant fibroblasts from PD patients with
      wild-type control fibroblasts using a variety of assays to gain a better
      understanding of the role of mitochondrial dysfunction in PD. To this end, dermal
      fibroblasts were obtained from three PD patients with homozygous whole exon
      deletions in parkin and three unaffected controls. Assays of mitochondrial
      respiration, mitochondrial network integrity, mitochondrial membrane potential,
      and cell growth were performed as informative markers of mitochondrial function.
      Surprisingly, it was found that mitochondrial respiratory rates were markedly
      higher in the parkin-mutant fibroblasts compared to control fibroblasts (p =
      0.0093), while exhibiting more fragmented mitochondrial networks (p = 0.0304).
      Moreover, cell growth of the parkin-mutant fibroblasts was significantly higher
      than that of controls (p = 0.0001). These unanticipated findings are suggestive
      of a compensatory mechanism to preserve mitochondrial function and quality
      control in the absence of parkin in fibroblasts, which warrants further
      investigation. 

PMID- 27034888
TI  - Methyl-Arginine Profile of Brain from Aged PINK1-KO+A53T-SNCA Mice Suggests
      Altered Mitochondrial Biogenesis.
AB  - Hereditary Parkinson's disease can be triggered by an autosomal dominant overdose
      of alpha-Synuclein (SNCA) or the autosomal recessive deficiency of PINK1. We
      recently showed that the combination of PINK1-knockout with overexpression of
      A53T-SNCA in double mutant (DM) mice potentiates phenotypes and reduces survival.
      Now we studied brain hemispheres of DM mice at age of 18 months in a hypothesis
      free approach, employing a quantitative label-free global proteomic mass
      spectrometry scan of posttranslational modifications focusing on methyl-arginine.
      The strongest effects were documented for the adhesion modulator CMAS, the mRNA
      decapping/deadenylation factor PATL1, and the synaptic plasticity mediator
      CRTC1/TORC1. In addition, an intriguing effect was observed for the splicing
      factor PSF/SFPQ, known to interact with the dopaminergic differentiation factor
      NURR1 as well as with DJ-1, the protein responsible for the autosomal recessive
      PARK7 variant of PD. CRTC1, PSF, and DJ-1 are modulators of PGC1alpha and of
      mitochondrial biogenesis. This pathway was further stressed by dysregulations of
      oxygen sensor EGLN3 and of nuclear TMPO. PSF and TMPO cooperate with dopaminergic
      differentiation factors LMX1B and NURR1. Further dysregulations concerned PRR18,
      TRIO, HNRNPA1, DMWD, WAVE1, ILDR2, DBNDD1, and NFM. Thus, we report selective
      novel endogenous stress responses in brain, which highlight early dysregulations
      of mitochondrial homeostasis and midbrain vulnerability. 

PMID- 27034889
TI  - Using Tractography to Distinguish SWEDD from Parkinson's Disease Patients Based
      on Connectivity.
AB  - Background. It is critical to distinguish between Parkinson's disease (PD) and
      scans without evidence of dopaminergic deficit (SWEDD), because the two groups
      are different and require different therapeutic approaches. Objective. The aim of
      this study was to distinguish SWEDD patients from PD patients using connectivity
      information derived from diffusion tensor imaging tractography. Methods.
      Diffusion magnetic resonance images of SWEDD (n = 37) and PD (n = 40) were
      obtained from a research database. Tractography, the process of obtaining neural
      fiber information, was performed using custom software. Group-wise differences
      between PD and SWEDD patients were quantified using the number of connected
      fibers between two regions, and correlation analyses were performed based on
      clinical scores. A support vector machine classifier (SVM) was applied to
      distinguish PD and SWEDD based on group-wise differences. Results. Four
      connections showed significant group-wise differences and correlated with the
      Unified Parkinson's Disease Rating Scale sponsored by the Movement Disorder
      Society. The SVM classifier attained 77.92% accuracy in distinguishing between
      SWEDD and PD using these identified connections. Conclusions. The connections and
      regions identified represent candidates for future research investigations. 

PMID- 27034890
TI  - Prevalence of Dog Erythrocyte Antigens 1, 4, and 7 in Podenco Ibicenco (Ibizan
      Hounds) from Ibiza Island.
AB  - The aims of this study were to evaluate the prevalence of Dog Erythrocyte
      Antigens (DEA) 1, 4, and 7 in Ibizan hounds, to compare the results with the
      prevalence of DEA in Spanish greyhounds, and to determine the risk of
      sensitization following the first transfusion of blood not typed for DEA 1 and
      the probability of an acute hemolytic reaction following a second incompatible
      transfusion using untyped DEA 1 blood. DEA 1, 4, and 7 status was determined in
      92 Ibizan hounds. Results were compared with the previously reported prevalence
      in Spanish greyhounds. The risks of sensitization and of a hemolytic transfusion
      reaction were determined amongst Ibizan hounds and between Ibizan hounds and
      Spanish greyhounds. The prevalence of DEA 1, 4, and 7 was 75%, 98.9%, and 25%,
      respectively. There was a significantly higher expression of DEA 1 and 7 in
      Ibizan hounds than in Spanish greyhounds. The probability of sensitization of a
      recipient dog to DEA 1 with transfusions amongst Ibizan hounds was 18.5% and
      between Ibizan hounds and Spanish greyhounds was 13.7%. The probability of an
      acute hemolytic reaction in each group was 3.5% and 1.9%, respectively. There is
      a higher prevalence of DEA 1 and 7 in Ibizan hounds than in other sighthounds. 

PMID- 27034891
TI  - Transition Metal Complexes of Naproxen: Synthesis, Characterization, Forced
      Degradation Studies, and Analytical Method Verification.
AB  - The aim of our current research was to synthesize some transition metal complexes
      of Naproxen, determine their physical properties, and examine their relative
      stability under various conditions. Characterizations of these complexes were
      done by 1H-NMR, Differential Scanning Calorimetry (DSC), FT-IR, HPLC, and
      scanning electron microscope (SEM). Complexes were subjected to acidic, basic,
      and aqueous hydrolysis as well as oxidation, reduction, and thermal degradation.
      Also the reversed phase high-performance liquid chromatography (RP-HPLC) method
      of Naproxen outlined in USP was verified for the Naproxen-metal complexes, with
      respect to accuracy, precision, solution stability, robustness, and system
      suitability. The melting points of the complexes were higher than that of the
      parent drug molecule suggesting their thermal stability. In forced degradation
      study, complexes were found more stable than the Naproxen itself in all
      conditions: acidic, basic, oxidation, and reduction media. All the HPLC
      verification parameters were found within the acceptable value. Therefore, it can
      be concluded from the study that the metal complexes of Naproxen can be more
      stable drug entity and offer better efficacy and longer shelf life than the
      parent Naproxen. 

PMID- 27034892
TI  - Evaluation of the Influence of Sulfur-Fumigated Paeoniae Radix Alba on the
      Quality of Si Wu Tang by Chromatographic and Chemometric Analysis.
AB  - An accurate and reliable method of high-performance liquid chromatographic
      fingerprint combining with multi-ingredient determination was developed and
      validated to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on
      the quality and chemical constituents of Si Wu Tang. Multivariate data analysis
      including hierarchical cluster analysis and principal component analysis, which
      integrated with high-performance liquid chromatographic fingerprint and multi
      ingredient determination, was employed to evaluate Si Wu Tang in a more objective
      and scientific way. Interestingly, in this paper, a total of 37 and 36 peaks were
      marked as common peaks in ten batches of Si Wu Tang containing sun-dried Paeoniae
      Radix Alba and ten batches of Si Wu Tang containing sulfur-fumigated Paeoniae
      Radix Alba, respectively, which indicated the changed fingerprint profile of Si
      Wu Tang when containing sulfur-fumigated herb. Furthermore, the results of
      simultaneous determination for multiple ingredients showed that the contents of
      albiflorin and paeoniflorin decreased significantly (P < 0.01) and the contents
      of gallic acid and Z-ligustilide decreased to some extent at the same time when
      Si Wu Tang contained sulfur-fumigated Paeoniae Radix Alba. Therefore, sulfur
      fumigation processing may have great influence on the quality of Chinese herbal
      prescription. 

PMID- 27034893
TI  - Virtual Instrument for Emissions Measurement of Internal Combustion Engines.
AB  - The gases emissions measurement systems in internal combustion engines are strict
      and expensive nowadays. For this reason, a virtual instrument was developed to
      measure the combustion emissions from an internal combustion diesel engine,
      running with diesel-biodiesel mixtures. This software is called virtual
      instrument for emissions measurement (VIEM), and it was developed in the platform
      of LabVIEW 2010(r) virtual programming. VIEM works with sensors connected to a
      signal conditioning system, and a data acquisition system is used as interface
      for a computer in order to measure and monitor in real time the emissions of O2,
      NO, CO, SO2, and CO2 gases. This paper shows the results of the VIEM programming,
      the integrated circuits diagrams used for the signal conditioning of sensors, and
      the sensors characterization of O2, NO, CO, SO2, and CO2. VIEM is a low-cost
      instrument and is simple and easy to use. Besides, it is scalable, making it
      flexible and defined by the user. 

PMID- 27034894
TI  - Trail without Catheter after Transurethral Resection of Prostate: Clamp It or
      Not?
AB  - Background. There has been argument between clinical practitioners about clamping
      catheter or not prior to its removal after transurethral resection of prostate
      (TURP). We conducted a clinical trial to assess whether clamping has any role in
      early bladder tone recovery particularly in patients who undergo TURP. Methods.
      Randomized clinical trial was conducted at a tertiary care hospital, Karachi from
      January 2014 to July 2015. Eighty-six study participants who underwent TURP were
      randomly allocated into two groups of 43 participants each. In Group I, patient's
      Foley catheter was not clamped prior to its removal and in Group II Foley
      catheter was clamped. Data of all subjects were analyzed using SPSS version 20.
      Results. There was no significant difference in age and weight of resected
      tissues between two groups. Among 4 patients in Group I who required
      recatheterization, 1 patient was discharged with catheter as compared to Group II
      in which 2 patients were discharged with catheter (P = 0.99). Only 1 patient
      (2.3%) in Group II had bleeding which required recatheterization. Length of stay
      was significantly affected by early and free removal of Foley catheter (P <
      0.001). Conclusion. The results of current study identified that clamping whether
      done or not had no significant impact on urinary retention. 

PMID- 27034895
TI  - Histomorphological and Immunohistochemical Reappraisal of Cutaneous Adnexal
      Tumours: A Hospital Based Study.
AB  - Background. Diagnosing adnexal tumours of the skin is a challenge due to their
      wide variety, infrequent occurrence in practice, and confusing morphological
      picture. Aims and Objectives. The present study aims to observe the spectrum of
      adnexal tumours at our institute and to evaluate them based on
      histomorphological, histochemical, and immunohistochemical methods either alone
      or in combination for proper identification and classification. Materials and
      Methods. A partly retrospective and partly prospective study was conducted on
      adnexal skin tumours over a period of 6 years. Relevant clinical profile was
      recorded. Histopathological examination was carried out and special stains were
      applied as and when required. Immunohistochemistry was performed where diagnosis
      with routine stains was not possible. Results. A total of 150 skin tumour
      biopsies were received. There were 87 keratotic tumours, 39 adnexal tumours, and
      24 melanocytic tumours. Amongst the adnexal tumours, 51.3% eccrine, 30.8%
      follicular, and 17.9% sebaceous tumours were seen. In five cases, histological
      diagnosis was troublesome where immunohistochemistry helped in making final
      diagnosis. Limitations. The sample size is small. Conclusion. Histomorphology is
      confirmatory in majority of the adnexal tumours but few rare lesions that mimic
      internal malignancy require a panel of immunomarkers to rule out other possible
      differentials. 

PMID- 27034896
TI  - Aegle marmelos Mediated Green Synthesis of Different Nanostructured Metal
      Hexacyanoferrates: Activity against Photodegradation of Harmful Organic Dyes.
AB  - Prussian blue analogue potassium metal hexacyanoferrate (KMHCF) nanoparticles
      Fe4[Fe(CN)6]3 (FeHCF), K2Cu3[Fe(CN)6]2 (KCuHCF), K2Ni[Fe(CN)6].3H2O (KNiHCF), and
      K2Co[Fe(CN)6] (KCoHCF) have been synthesized using plant based biosurfactant
      Aegle marmelos (Bael) and water as a green solvent. It must be emphasized here
      that no harmful reagent or solvent was used throughout the study. Plant extracts
      are easily biodegradable and therefore do not cause any harm to the environment.
      Hence, the proposed method of synthesis of various KMHCF nanoparticles followed a
      green path. The synthesized nanoparticles were characterized by powder X-ray
      diffraction (PXRD), Field-Emission Scanning Electron Microscopy (FE-SEM),
      Transmission Electron Microscopy (TEM), and Fourier Transform Infrared
      Spectroscopy (FT-IR). MHCF nanoparticles were used for the photocatalytic
      degradation of toxic dyes like Malachite Green (MG), Eriochrome Black T (EBT),
      Methyl Orange (MO), and Methylene Blue (MB). Under optimized reaction conditions,
      maximum photocatalytic degradation was achieved in case of KCuHCF nanoparticles
      mediated degradation process (MG: 96.06%, EBT: 83.03%, MB: 94.72%, and MO:
      63.71%) followed by KNiHCF (MG: 95%, EBT: 80.32%, MB: 91.35%, and MO: 59.42%),
      KCoHCF (MG: 91.45%, EBT: 78.84%, MB: 89.28%, and MO: 58.20%). 

PMID- 27034897
TI  - Effect of the Purple Corn Beverage "Chicha Morada" in Composite Resin during
      Dental Bleaching.
AB  - During dental bleaching the staining potential of the surface would increase.
      This study aims to evaluate the staining susceptibility of one bleached composite
      resin after the exposure to three different beverages: Peruvian purple corn based
      beverage (chicha morada), green tea, and distilled water. Thirty disk-shaped
      specimens of one nanofill composite resin were prepared. The specimens were then
      divided into six groups (n = 5): purple corn (P), purple corn + bleaching (PB),
      green tea (T), green tea + bleaching (TB), distilled water (W), and distilled
      water + bleaching (WB). In groups that received bleaching, two sessions of
      bleaching with 35% hydrogen peroxide were done. Following bleaching, specimens
      were exposed to each liquid thirty minutes daily. Color was measured with a
      digital spectrophotometer. For statistical analysis, color measurement
      differences between the obtained results were used: during bleaching, after
      bleaching, and during + after bleaching. Two-way ANOVA was used to compare the
      color changes in the resins of all groups (p < 0.05). We conclude that all the
      evaluated beverages produced changes of color in the composite resin regardless
      of the bleaching procedure. However, purple corn was the only beverage that
      caused a perceptible color change (DeltaE > 3.3). 

PMID- 27034898
TI  - In Silico Analysis of Arabidopsis thaliana Peroxisomal 6-Phosphogluconate
      Dehydrogenase.
AB  - NADPH, whose regeneration is critical for reductive biosynthesis and
      detoxification pathways, is an essential component in cell redox homeostasis.
      Peroxisomes are subcellular organelles with a complex biochemical machinery
      involved in signaling and stress processes by molecules such as hydrogen peroxide
      (H2O2) and nitric oxide (NO). NADPH is required by several peroxisomal enzymes
      involved in beta-oxidation, NO, and glutathione (GSH) generation. Plants have
      various NADPH-generating dehydrogenases, one of which is 6-phosphogluconate
      dehydrogenase (6PGDH). Arabidopsis contains three 6PGDH genes that probably are
      encoded for cytosolic, chloroplastic/mitochondrial, and peroxisomal isozymes,
      although their specific functions remain largely unknown. This study focuses on
      the in silico analysis of the biochemical characteristics and gene expression of
      peroxisomal 6PGDH (p6PGDH) with the aim of understanding its potential function
      in the peroxisomal NADPH-recycling system. The data show that a group of plant
      6PGDHs contains an archetypal type 1 peroxisomal targeting signal (PTS), while in
      silico gene expression analysis using affymetrix microarray data suggests that
      Arabidopsis p6PGDH appears to be mainly involved in xenobiotic response, growth,
      and developmental processes. 

PMID- 27034899
TI  - Cytoprotective Effect of Lygodium venustum Sw. (Lygodiaceae) against Mercurium
      Chloride Toxicity.
AB  - Mercury is a very dangerous metal when humans come into contact with it, whether
      through the air or skin or by ingestion. The aim of this work was to investigate
      the possible effects of the ethanol extract and fractions of Lygodium venustum
      Sw. against mercurium chloride toxicity towards Escherichia coli strain
      ATCC25922. The polyphenols and flavonoids present in the extract and fractions
      were quantified in mg equivalent of gallic acid/g sample and mg equivalent of
      quercetin/g sample, respectively. The in vitro FRAP method demonstrated the
      antioxidant activity of the samples. The antibacterial activity of the natural
      products was evaluated by microdilution method and by assays to elucidate the
      possible cytoprotective action when combining the natural products samples and
      mercurium chloride, utilizing the extract and fractions at a subinhibitory
      concentration. The results obtained in this work indicate that the ethanol
      extract and fractions of L. venustum are an alternative source of natural
      products with cytoprotective action, where this protection is correlated with
      antioxidant and chelating activity, due to the presence of total phenols and
      flavonoids. 

PMID- 27034900
TI  - Is Recurving an Effective Strategy of Trifolium repens L. to Augment
      Reproduction?
AB  - Flowers of Trifolium repens L. show recurving. We, therefore, studied whether
      this is an effective strategy employed by the species to augment reproduction.
      For this, fifty plants of the species were tagged and monitored. This included
      twenty control and twenty constrained to recurve. The remaining 10 plants were
      covered with a net to limit cross-pollination. Daily observations on the plants
      were recorded. No significant difference in the number of flowers per
      inflorescence between control and constrained plants was found. However, a
      significant difference (p < 0.001) in the number of seeds produced by control
      (68.35 +/- 3.92) and constrained plants (22.25 +/- 1.35) was observed. Three
      times more seeds, without compromising on seed mass (p > 0.05), were produced in
      the control plants. No seeds were produced in the flowers that were netted. Thus,
      recurving appears to help T. repens in reproduction. 

PMID- 27034901
TI  - Oral Health Knowledge, Attitude, and Approaches of Pre-Primary and Primary School
      Teachers in Mumbai, India.
AB  - Background. School teachers have an internationally recognized potential role in
      school-based dental education and considerable importance has therefore been
      attributed to their dental knowledge. The objectives of this study were to
      determine the oral health related knowledge, attitudes, and approaches of pre
      primary and primary school teachers in the city of Mumbai. Methods. The
      descriptive cross-sectional study was conducted in the suburban regions of Mumbai
      using a self-administered questionnaire and involved 511 teachers. Results.
      Teachers demonstrated inappropriate or incomplete knowledge regarding children's
      oral health. Only 53.2% knew that an individual has two sets of dentition.
      Moreover, only 45.4% of the teachers knew that a primary dentition consists of 20
      teeth. Only 56.9% of the teachers asked their children to clean their mouth after
      snacking during school hours. 45.0% of the teachers were unaware of fluoridated
      tooth pastes whilst 78.9% of them were unaware of school water fluoridation
      programmes. Also, 54.8% of the teachers never discussed the oral health of
      children with their parents during parents meet. Conclusions. The studied school
      teachers demonstrated incomplete oral health knowledge, inappropriate oral
      practices, and unfavourable approaches to children's oral health. There is a
      definite and immediate need for organized training of school teachers on basic
      oral health knowledge. 

PMID- 27034902
TI  - Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of
      Mice.
AB  - Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one
      of the top five most commonly used nanoparticles worldwide. Recently, various
      studies referred to their toxic potential on various organs using different
      treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500
      mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at
      24 h, 7 days, or 14 days after the last treatment. The present results report
      that exposure to TiO2NPs produces mild to moderate changes in the
      cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet
      assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct
      sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to
      inherited forms of the Alzheimer's disease. Therefore, from these findings, the
      present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue
      which in turn might lead to Alzheimer's disease incidence. 

PMID- 27034903
TI  - Periodontal Health Status among Patients with Behcet's Disease.
AB  - We aimed to evaluate the relationship of individual periodontal parameters with
      the severity of Behcet's disease (BD) and attempt to find the correlation between
      chronic periodontitis and BD. In this study, 74 registered subjects attending
      Behcet's clinic with BD symptoms were recruited. The diagnosis was based on the
      criteria presented by the international study group for BD (ISG) and the total
      clinical severity score was determined for each patient. All individuals
      underwent clinical examination to assess oral and periodontal status and presence
      of oral ulcers. Periodontal clinical parameters of bleeding on probing (BOP),
      probing depth (PD), and clinical attachment level (CAL) and also hygiene index
      (HI) and decayed, missing, and filled (DMF) teeth were noted and analyzed to
      assess the correlation with severity of BD. There was no significant correlation
      between DMF and severity of BD. The strong association was found between
      periodontal parameters (BOP, PD, and CAL) and the severity of BD (P < 0.001). It
      seems that relation of BD to oral health is higher up in severe forms of BD and
      periodontal diseases. Clinical association between the diseases might be due to a
      common underlying etiopathogenesis of periodontitis and BD. 

PMID- 27034904
TI  - Mycoplasma genitalium: An Emerging Sexually Transmitted Infection.
AB  - Mycoplasma genitalium has been recognized as a cause of male urethritis, and
      there is now evidence suggesting that it causes cervicitis and pelvic
      inflammatory disease in women. M. genitalium is a slow growing organism, and,
      with the advent of nucleic acid amplification test (NAAT), more studies are being
      performed, and knowledge about the pathogenicity of this organism elucidated.
      With NAAT detection, treatment modalities have been studied, and the next
      challenge is to determine the most effective antimicrobial therapy. Doxycycline,
      the first-line antibiotic for urethritis, is largely ineffective in the treatment
      of M. genitalium and furthermore, resistance to macrolide has also emerged. The
      most effective drug is Moxifloxacin although there are emerging reports of
      resistance to it in various parts of the world. This paper not only highlights
      the current research and knowledge, but also reviews the diversity of health
      implications on the health of men and women infected with M. genitalium.
      Alternate antibiotics and the impact of M. genitalium on infertility are areas
      that require more studies as we continue to research into this microorganism. 

PMID- 27034905
TI  - Geohelminth Infections and Nutritional Status of Preschool Aged Children in a
      Periurban Settlement of Ogun State.
AB  - This study assessed the geohelminth and nutritional status of preschoolers in a
      periurban community of Ogun state. Fresh stool specimens were collected for
      laboratory analysis, processed using ether concentration method, and examined
      under the microscope for geohelminth ova. Demographic characteristics and daily
      nutrient intake of children were subjectively assessed during an interview
      session with parents, following anthropometric data collection. Data obtained
      were analysed using a statistical software for Windows. Nutritional indicators
      such as underweight, stunting, and wasting were computed from anthropometric
      data. Results showed an overall prevalence of 39.2% and 12.4% for Ascariasis and
      Hookworm infection, respectively, with no significant difference (P > 0.05)
      between the sexes. Prevalence of nutritional indicators was 52.6%, 35.1%, 34.0%,
      and 9.3% for underweight, stunting, wasting, and thinness conditions,
      respectively. A good proportion of the malnourished preschoolers were free of
      Ascaris infection but infected with Hookworm parasite. The adverse effect of
      geohelminth infection cannot still be ignored in impaired growth, reduced
      survival, poor development, and cognitive performance of preschoolers. Therefore
      promotion of adequate health education program on measures of preventing
      geohelminth infections is needed. 

PMID- 27034906
TI  - Gene Prioritization by Integrated Analysis of Protein Structural and Network
      Topological Properties for the Protein-Protein Interaction Network of
      Neurological Disorders.
AB  - Neurological disorders are known to show similar phenotypic manifestations like
      anxiety, depression, and cognitive impairment. There is a need to identify shared
      genetic markers and molecular pathways in these diseases, which lead to such
      comorbid conditions. Our study aims to prioritize novel genetic markers that
      might increase the susceptibility of patients affected with one neurological
      disorder to other diseases with similar manifestations. Identification of
      pathways involving common candidate markers will help in the development of
      improved diagnosis and treatments strategies for patients affected with
      neurological disorders. This systems biology study for the first time
      integratively uses 3D-structural protein interface descriptors and network
      topological properties that characterize proteins in a neurological protein
      interaction network, to aid the identification of genes that are previously not
      known to be shared between these diseases. Results of protein prioritization by
      machine learning have identified known as well as new genetic markers which might
      have direct or indirect involvement in several neurological disorders. Important
      gene hubs have also been identified that provide an evidence for shared molecular
      pathways in the neurological disease network. 

PMID- 27034907
TI  - A Comprehensive Review on Methodologies Employed for Visual Evoked Potentials.
AB  - Visual information is fundamental to how we appreciate our environment and
      interact with others. The visual evoked potential (VEP) is among those evoked
      potentials that are the bioelectric signals generated in the striate and
      extrastriate cortex when the retina is stimulated with light which can be
      recorded from the scalp electrodes. In the current paper, we provide an overview
      of the various modalities, techniques, and methodologies which have been employed
      for visual evoked potentials over the years. In the first part of the paper, we
      cast a cursory glance on the historical aspect of evoked potentials. Then the
      growing clinical significance and advantages of VEPs in clinical disorders have
      been briefly described, followed by the discussion on the earlier and currently
      available methods for VEPs based on the studies in the past and recent times.
      Next, we mention the standards and protocols laid down by the authorized
      agencies. We then summarize the recently developed techniques for VEP. In the
      concluding section, we lay down prospective research directives related to
      fundamental and applied aspects of VEPs as well as offering perspectives for
      further research to stimulate inquiry into the role of visual evoked potentials
      in visual processing impairment related disorders. 

PMID- 27034908
TI  - Xyloglucan Based In Situ Gel of Lidocaine HCl for the Treatment of Periodontosis.
AB  - The present study was aimed at formulating thermoreversible in situ gel of local
      anesthetic by using xyloglucan based mucoadhesive tamarind seed polysaccharide
      (TSP) into periodontal pocket. Temperature-sensitive in situ gel of lidocaine
      hydrochloride (LH) (2% w/v) was formulated by cold method. A full 3(2) factorial
      design was employed to study the effect of independent variables concentrations
      of Lutrol F127 and TSP to optimize in situ gel. The dependent variables evaluated
      were gelation temperature (Y 1) and drug release (Y 2). The results revealed the
      surface pH of 6.8, similar to the pH of saliva. Viscosity study showed the marked
      increase in the viscosity of gel at 37 degrees C due to sol-gel conversion. TSP
      was found to act as good mucoadhesive component to retain gel at the site of
      application in dental pocket. Gelation of formulation occurred near to body
      temperature. In vitro study depicted the fast onset of drug action but lasting
      the release (90%) till 2 h. Formulation F7 was considered as optimized batch,
      containing 18% Lutrol F127 and 1% tamarind seed polysaccharide. Thus, lidocaine
      hydrochloride thermoreversible in situ gel offered an alternative to painful
      injection therapy of anesthesia during dental surgery, with fast onset of
      anesthetic action lasting throughout the dental procedure. 

PMID- 27034909
TI  - Hypothesis Testing of Population Percentiles via the Wald Test with Bootstrap
      Variance Estimates.
AB  - Testing the equality of percentiles (quantiles) between populations is an
      effective method for robust, nonparametric comparison, especially when the
      distributions are asymmetric or irregularly shaped. Unlike global nonparametric
      tests for homogeneity such as the Kolmogorv-Smirnov test, testing the equality of
      a set of percentiles (i.e., a percentile profile) yields an estimate of the
      location and extent of the differences between the populations along the entire
      domain. The Wald test using bootstrap estimates of variance of the order
      statistics provides a unified method for hypothesis testing of functions of the
      population percentiles. Simulation studies are conducted to show performance of
      the method under various scenarios and to give suggestions on its use. Several
      examples are given to illustrate some useful applications to real data.

PMID- 27034910
TI  - Social Factors and Healthy Aging: Findings from the Louisiana Healthy Aging Study
      (LHAS).
AB  - Social behaviors are associated with health outcomes in later life. The authors
      examined relationships among social and physical activities and health in a
      lifespan sample of adults (N = 771) drawn from the Louisiana Healthy Aging Study
      (LHAS). Four age groups were compared: younger (21-44 years), middle-aged (45-64
      years), older (65-84 years), and oldest-old adults (85 to 101 years). Linear
      regression analyses indicated that physical activity, hours spent outside of the
      house, and social support were significantly associated with self-reported
      health, after controlling for sociodemographic factors. Number of clubs was
      significantly associated with objective health status, after controlling for
      sociodemographic factors. These data indicate that social and physical activities
      remain an important determinant of self-perceived health into very late
      adulthood. Implications of these data for current views on successful aging are
      discussed.

PMID- 27034911
TI  - Clarifying the Behavioral Economics of Social Anxiety Disorder: Effects of
      Interpersonal Problems and Symptom Severity on Generosity.
AB  - Social anxiety disorder is associated with lower interpersonal warmth, possibly
      explaining its associated interpersonal impairment. Across two samples, we
      attempted to replicate previous findings that the disorder's constraint of
      interpersonal warmth can be detected via behavioral economic tasks. We also
      tested the test-retest stability of task indices. Results indicated that factors
      associated with social anxiety disorder (and not the disorder itself), such as
      the severity of social anxiety and more extreme interpersonal problems, lead to
      less generous behavior on the economic task examined. Results were clearest
      regarding fine-grained indices derived from latent trajectories. Unexpectedly,
      the combination of generalized anxiety disorder and higher depression also
      restricted generosity. Two of three indices showed acceptable test-retest
      stability. Maladaptive giving behavior may be a treatment target to improve
      interpersonal functioning in psychiatric disorders; therefore, future work should
      more precisely characterize behavioral economic tasks, including basic
      psychometric work (i.e., tests of reliability and validity).

PMID- 27034912
TI  - Questioning kindling: An analysis of cycle acceleration in unipolar depression.
AB  - The kindling hypothesis for depression predicts that with more recurrences, the
      interval between successive recurrences decreases. Studies with unipolar and
      bipolar samples generally have been consistent with this premise. However,
      previous research is subject to a statistical artifact. Slater's fallacy
      maintains that these intermorbid intervals appear to decrease because highly
      recurrent individuals with consistently shorter intervals become a larger
      proportion of the remaining sample with each recurrence. Correcting for this
      bias, research on bipolar disorder no longer evidences such an effect. We
      predicted similar results for unipolar depression when correcting for this bias,
      and proposed an alternative model: individuals who are highly recurrent have
      consistently shorter intermorbid periods, even following the very first lifetime
      episode. As predicted, correcting for Slater's fallacy removed the appearance of
      decreasing intermorbid intervals. Further, highly recurrent individuals exhibited
      shorter intermorbid intervals in general, and for the very first interval,
      supporting the alternative model.

PMID- 27034913
TI  - Three-Phase Time-Multiplexed Planar Power Transmission to Distributed Implants.
AB  - A platform has been presented for wireless powering of receivers (Rx's) that are
      arbitrarily distributed over a large area. A potential application could be
      powering of small Rx implants, distributed over large areas of the brain. The
      transmitter (Tx) consists of three overlapping layers of hexagonal planar spiral
      coils (hex-PSC) that are horizontally shifted to provide the strongest and most
      homogeneous electromagnetic flux coverage. The three-layer hex-PSC array is
      driven by a three-phase time-division-multiplexed power Tx that takes the
      advantage of the carrier phase shift, coil geometries, and Rx time constant to
      homogeneously power the arbitrarily distributed Rx's regardless of their
      misalignments. The functionality of the proposed three-phase power transmission
      concept has been verified in a detailed scaled-up high-frequency structure
      simulator Advanced Design System simulation model and measurement setup, and
      compared with a conventional Tx. The new Tx delivers 5.4 mW to each Rx and
      achieves, on average, 5.8% power transfer efficiency to the Rx at the worst case
      90 degrees  angular misalignment, compared with 1.4% by the conventional Tx.

PMID- 27034914
TI  - The Structural and Functional Connectome and Prediction of Risk for Cognitive
      Impairment in Older Adults.
AB  - The human connectome refers to a comprehensive description of the brain's
      structural and functional connections in terms of brain networks. As the field of
      brain connectomics has developed, data acquisition, subsequent processing and
      modeling, and ultimately the representation of the connectome have become better
      defined and integrated with network science approaches. In this way, the human
      connectome has provided a way to elucidate key features of not only the healthy
      brain but also diseased brains. The field has quickly evolved, offering insights
      into network disruptions that are characteristic for specific neurodegenerative
      disorders. In this paper, we provide a brief review of the field of brain
      connectomics, as well as a more in-depth survey of recent studies that have
      provided new insights into brain network pathologies, including those found in
      Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and
      finally in people classified as being "at risk". Until the emergence of brain
      connectomics, most previous studies had assessed neurodegenerative diseases
      mainly by focusing on specific and dispersed locales in the brain. Connectomics
      based approaches allow us to model the brain as a network, which allows for
      inferences about how dynamic changes in brain function would be affected in
      relation to structural changes. In fact, looking at diseases using network theory
      gives rise to new hypotheses on mechanisms of pathophysiology and clinical
      symptoms. Finally, we discuss the future of this field and how understanding both
      the functional and structural connectome can aid in gaining sharper insight into
      changes in biological brain networks associated with cognitive impairment and
      dementia.

PMID- 27034915
TI  - Dimensionality of Cognitions in Behavioral Addiction.
AB  - Cognitive constructs provide conceptual frameworks for transpathological
      characterization and improved phenotyping of apparently disparate psychiatric
      groups. This dimensional approach can be applied to the examination of
      individuals with behavioral addictions, for example, towards gambling, video
      games, the internet, food, and sex, allowing operationalization of core deficits.
      We use this approach to review constructs such as impulsivity, compulsivity, and
      attention regulation, which may be most relevant, applicable, and successful for
      the understanding and subsequent treatment of the addictions.

PMID- 27034916
TI  - A semi-automated workflow solution for multimodal neuroimaging: application to
      patients with traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major cause of mortality and morbidity, placing
      a significant financial burden on the healthcare system worldwide. Non-invasive
      neuroimaging technologies have been playing a pivotal role in the study of TBI,
      providing important information for surgical planning and patient management.
      Advances in understanding the basic mechanisms and pathophysiology of the brain
      following TBI are hindered by a lack of reliable image analysis methods for
      accurate quantitative assessment of TBI-induced structural and pathophysiological
      changes seen on anatomical and functional images obtained from multiple imaging
      modalities. Conventional region-of-interest (ROI) analysis based on manual
      labeling of brain regions is time-consuming and the results could be inconsistent
      within and among investigators. In this study, we propose a workflow solution
      framework that combined the use of non-linear spatial normalization of structural
      brain images and template-based anatomical labeling to automate the ROI analysis
      process. The proposed workflow solution is applied to dynamic PET scanning with
      15O-water (0-10 min) and 18F-FDDNP (0-6 min) for measuring cerebral blood flow in
      patients with TBI.

PMID- 27034917
TI  - Oxidative stress under ambient and physiological oxygen tension in tissue
      culture.
AB  - Oxygen (O2) levels range from 2-9% in vivo. However, cell culture experiments are
      performed at atmospheric O2 levels (21%). Oxidative stress due to generation of
      reactive oxygen species (ROS) in cells cultured at higher than physiological
      levels is implicated in multitude of deleterious effects including DNA damage,
      genomic instability and senescence. In addition, oxidative stress activates redox
      sensitive transcription factors related to inflammatory signaling and apoptotic
      signaling. Furthermore, several chromatin-modifying enzymes are affected by ROS,
      potentially impacting epigenetic regulation of gene expression. While primary
      cells are cultured at lower O2 levels due to their inability to grow at higher
      O2, the immortalized cells, which display no such apparent growth difficulties,
      are typically cultured at 21% O2. This review will provide an overview of issues
      associated with increased oxygen levels in in vitro cell culture and point out
      the benefits of using lower levels of oxygen tension even for immortalized cells.

PMID- 27034918
TI  - Image-Guided Hyaluronic Acid Injection and Knee Bracing Significantly Improve
      Clinical Outcomes for High-Grade Osteoarthritis.
AB  - BACKGROUND: Intra-articular hyaluronic acid (HA) injection is an intermediate
      option between analgesics and knee joint replacement in patients with
      osteoarthritis (OA). Our objective was to test whether image-guided HA injections
      may improve knee OA outcomes after 6 months of treatment independent of potential
      covariates. METHODS: This is a retrospective case series with multivariate
      outcome-based analysis of 207 consecutive adult patients with mild to severe knee
      OA treated at a single out-patient clinic employing fluoroscopy-guided HA
      injections. We employed a customized pain (scored 0-10) and function (scored 0
      120) questionnaire based on the Likert scale to compare baseline scores with 6
      month outcomes. Linear and logistic (based on >9-point score improvement)
      regression analysis was used to adjust for potential covariates, including grade
      of disease, patient age, gender, body mass index, smoking history, medical
      history (e.g., diabetes or heart disease), use of daily pain medications, fish
      oil supplementation, knee bracing, and physical therapy. RESULTS: Significant
      covariates included OA grade, knee bracing, and analgesic use. Most of the study
      subjects were women (124/207, 60 %) and obese (113/207, 55 %). Clinically
      significant improvements in index scores (>9 points) at 6 months were observed in
      more than 50 % of cases post-image-guided HA injection. Regression analysis
      revealed a complimentary affect with knee bracing, especially in severe grade 4
      disease (odds ratio 5.5 [1.14-27.0], P < 0.05). Daily analgesic use reflected a
      poor clinical response to treatment. CONCLUSIONS: Our data suggest image-guided
      HA injections coupled with knee bracing may benefit patients with moderate to
      severe knee osteoarthritis. KEY POINTS: Image-guided hyaluronic acid injections
      significantly improve clinical outcomes at 6 months for mild, moderate, and
      severe knee osteoarthritis.Knee bracing is a significant covariate for clinical
      improvement in severe grade 4 disease.Daily analgesic use is associated with high
      grade disease and less clinical improvement.

PMID- 27034919
TI  - Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute
      Inflammatory Responses.
AB  - BACKGROUND: The study aims to compare how work-to-rest ratio (W:R) influences
      insulin sensitivity (Si) and inflammatory responses following one session of
      sprint interval training (SIT). METHODS: Thirteen men and two women completed a
      cross-over comparison of two SIT interventions-Tabata (TAB), 10 * 20-s sprints/10
      s rest, and Wingate (WIN), 5 * 30-s sprints with 270-s rest. IL-6, IL-10, and TNF
      alpha were assessed at baseline, immediately following, and 1 h after SIT, as
      well as prior to the 24-h post-exercise oral glucose tolerance tests (OGTTs).
      RESULTS: Participants were 23.8 (+/-3.5) years old and 180.0 (+/-10.2) cm tall,
      weighed 78.5 (13.0) kg, and had 16.9 (+/-6.5) % body fat, with a mean VO2Peak of
      42.0 (+/-7.9) ml kg-1 min-1. There were no differences in total work (kJ) between
      TAB (64.7 +/- 12.0) and WIN (68.0 +/- 15.0). Mean (+/-95 % CI) Si 24 h changed 
      2.8 (-5.1, -0.5) from baseline after TAB and -3.9 (-6.9, -0.9) after WIN.
      Cytokines were measured in pg ml-1 and expressed as mean change (+/-95 % CI). IL
      6 increased significantly immediately following SIT for TAB 0.70 (0.23, 1.17),
      and WIN 1.11 (0.60, 1.62), and remained elevated 1 h post SIT for TAB 1.10 (0.37,
      1.83), and WIN 0.95 (0.26, 1.65). IL-10 showed a significant positive change
      immediately following exercise for TAB 1.53 (0.77, 2.29) and WIN 1.59 (0.58,
      2.59). TNF-alpha also increased immediately both TAB 3.26 (1.57, 4.96) and WIN
      3.05 (0.56, 5.54) and was directly proportional to IL-10 (r = 0.64, p < 0.0001).
      CONCLUSIONS: W:R did not alter either the inflammatory or metabolic response
      following SIT nor does SIT improve 24-h Si, despite increased levels of IL-10.

PMID- 27034920
TI  - Does this patient have pheochromocytoma? A systematic review of clinical signs
      and symptoms.
AB  - CONTEXT: Pheochromocytoma is a rare disease but with high mortality if it is not
      being diagnosed early. Several biochemical tests with high accuracy have been
      obtained, but the clinical threshold for request of these tests is not determined
      clearly. OBJECTIVES: To determine the Likelihood Ratios of clinical symptoms and
      signs in diagnosing pheochromocytoma. And also meta-analysis of their sensitivity
      in this disease. DATA SOURCES: MEDLINE was searched for relevant English-language
      articles dated 1960 to February 2014. Bibliographies were searched to find
      additional articles. STUDY SELECTION: We included original studies describing the
      sensitivity and/or likelihood ratios of signs and symptoms in clinical suspicion
      of pheochromocytoma. Their method of diagnosis should have been based on
      pathology. We excluded specific subtypes or syndromes related to
      pheochromocytoma, or specific ages or gender. Also we excluded studies before
      1993 (JNC5) which no definition of hypertension was presented. 37 articles were
      chosen finally. DATA EXTRACTION: Two authors reviewed data from articles
      independently and gave discrepancies to third author for decision. The aim was
      extraction of raw numbers of patients having defined signs or symptoms, and draw
      2 * 2 tables if data available. We meta-analyzed sensitivities by Statsdirect and
      Likelihood Ratios by Meta-disc soft wares. Because our data was heterogeneous
      based on I(2) > 50 % (except negative Likelihood ratio of hypertension), we used
      random effect model for doing meta-analysis. We checked publication bias by
      drawing Funnel plot for each sign/symptom, and also Egger test. DATA SYNTHESIS:
      The most prevalent signs and symptoms reported were hypertension (pooled
      sensitivity of 80.7 %), headache (pooled sensitivity of 60.4 %), palpitation
      (pooled sensitivity of 59.3 %) and diaphoresis (pooled sensitivity of 52.4 %).
      The definition of orthostatic hypotension was different among studies. The
      sensitivity was 23-50 %. Paroxysmal hypertension, chest pain, flushing, and
      weakness were the signs/symptoms which had publication bias based on Funnel plot
      and Egger test (P value < 0.05). Seven of the articles had control group, and
      could be used for calculating LR of signs/symptoms. Diaphoresis (LR+ 2.2, LR-
      0.45), Palpitation (LR+ 1.9, LR- 0.52) and headache (LR+ 1.6, LR- 0.24) were
      significant symptoms in clinical diagnosis of pheochromocytoma. Other signs and
      symptoms had been reported in only one study and could not have been meta
      analyzed. Classic triad of headache, palpitation and diaphoresis in hypertensive
      patients had the LR+ 6.312 (95 % CI 0.217-183.217) and LR- 0.139 (95 % CI 0.059
      0.331). Surprisingly, hypertension was not important in clinical suspicion of
      pheochromocytoma, and even normotension increased the probability of the disease.
      CONCLUSIONS: By available data, there is no single clinical finding that has
      significant value in diagnosis or excluding pheochromocytoma. Combination of
      certain symptoms, signs and para-clinical exams is more valuable for physicians.
      Further studies should be done, to specify the value of clinical findings. Until
      that time the process of diagnosis will be based on clinical suspicion and lab
      tests followed by related imaging.

PMID- 27034921
TI  - The Relation between Psychiatric Diagnoses and Constipation in Hospitalized
      Patients: A Cross-Sectional Study.
AB  - Objective. Constipation is a prevalent problem in patients with psychiatric
      disorders; it reduces quality of life and may lead to severe complications. The
      prevalence distribution of constipation across all psychiatric diagnoses in
      patients with severe mental illness (SMI) has hardly been studied. The aim of
      this study is to estimate the association between psychiatric disorders and
      constipation in SMI inpatients. Methods. The strength of the association between
      constipation (based on use of laxatives) and DSM-IV psychiatric diagnosis was
      studied in a cross-sectional study with "adjustment disorders" as the reference
      group. The association was analyzed using logistic regression. Results. Of the
      4728 patients, 20.3% had constipation. In the stratum of patients older than 60
      years, all psychiatric categories except for substance related disorders were
      significantly associated with a higher prevalence of constipation (odds ratios
      ranging from 3.38 to 6.52), whereas no significant associations were found in the
      stratum of patients between 18 and 60 years (odds ratios ranging from 1.00 to
      2.03). Conclusion. In the elderly, all measured psychiatric diagnoses are
      strongly associated with an increased prevalence of constipation. Physicians
      should be extra alert for constipation in SMI patients, independent of specific
      psychiatric diagnoses. 

PMID- 27034922
TI  - Use of Posttranscription Gene Silencing in Squash to Induce Resistance against
      the Egyptian Isolate of the Squash Leaf Curl Virus.
AB  - Squash leaf curl virus (SqLCV) is a bipartite begomovirus affecting squash
      plants. It is transmitted by whitefly Bemisia tabaci biotype B causing severe
      leaf curling, vein banding, and molting ending by stunting. In this study full
      length genomic clone of SqLCV Egyptian isolated and posttranscriptional gene
      silencing (PTGS) has been induced to develop virus resistance. The Noubaria SqLCV
      has more than 95% homology with Jordon, Israel, Lebanon, Palestine, and Cairo
      isolates. Two genes fragment from SqLCV introduced in sense and antisense
      orientations using pFGC5049 vector to be expressed as hairpin RNA. The first
      fragment was 348 bp from replication associated protein gene (Rep). The second
      fragment was 879 bp representing the full sequence of the movement protein gene
      (BC1). Using real-time PCR, a silencing record of 97% has been recorded to
      Rep/TrAP construct; as a result it has prevented the appearance of viral symptoms
      in most tested plants up to two months after infection, while construct
      containing the BC1 gene scored a reduction in the accumulation of viral genome
      expression as appearing in real-time PCR results 4.6-fold giving a silencing of
      79%, which had a positive effect on symptoms development in most tested plants. 

PMID- 27034923
TI  - Application of Principal Component Analysis in Automatic Localization of Optic
      Disc and Fovea in Retinal Images.
AB  - A retinal image has blood vessels, optic disc, fovea, and so forth as the main
      components of an image. Segmentation of these components has been investigated
      extensively. Principal component analysis (PCA) is one of the techniques that
      have been applied to segment the optic disc, but only a limited work has been
      reported. To our knowledge, fovea segmentation problem has not been reported in
      the literature using PCA. In this paper, we are presenting the segmentation of
      optic disc and fovea using PCA. The PCA was trained on optic discs and foveae
      using ten retinal images and then applied on seventy retinal images with a
      success rate of 97% in case of optic discs and 94.3% in case of fovea.
      Conventional algorithms feed one patch at a time from a test retinal image, and
      the next patch separated by one pixel part is fed. This process is continued till
      the full image area is covered. This is time consuming. We are suggesting
      techniques to cut down the processing time with the help of binary vessel tree of
      a given test image. Results are presented to validate our idea. 

PMID- 27034924
TI  - Drying Characteristics and Physical and Nutritional Properties of Shrimp Meat as
      Affected by Different Traditional Drying Techniques.
AB  - The influence of different drying methods on physical and nutritional properties
      of shrimp meat was investigated in this study. Peeled shrimps were dried
      separately using an air-oven dryer and a tunnel solar dryer. The drying profile
      of shrimp meat was determined in the two drying systems by monitoring moisture
      loss over the drying period. Changes in color, proximate composition, and
      rehydration capacity were assessed. The rate of moisture removal during solar
      drying was faster than the air-oven drying. The development of red color during
      drying was comparable among the two methods, but solar-dried shrimps appeared
      darker (L (*) = 47.4) than the air-oven-dried (L (*) = 49.0). Chemical analysis
      indicated that protein and fat made up nearly 20% and 2% (wb) of the shrimp meat,
      respectively. Protein and ash content of shrimp meat dried under the two dryer
      types were comparable but fat was significantly (p < 0.05) higher in oven-dried
      meat (2.1%), compared to solar-dried meat (1.5%). Although rehydration behavior
      of shrimp from the two drying systems followed a similar pattern, solar-dried
      shrimp absorbed moisture more rapidly. The results have demonstrated that
      different approaches to drying may affect the physical and nutritional quality of
      shrimp meat differently. 

PMID- 27034925
TI  - A Polyethylenimine-Containing and Transferrin-Conjugated Lipid Nanoparticle
      System for Antisense Oligonucleotide Delivery to AML.
AB  - Limited success of antisense oligonucleotides (ASO) in clinical anticancer
      therapy calls for more effective delivery carriers. The goal of this study was to
      develop a nanoparticle system for delivery of ASO G3139, which targets mRNA of
      antiapoptotic protein Bcl-2, to acute myeloid leukemia (AML) cells. The
      synthesized nanoparticle Tf-LPN-G3139 contained a small molecular weight
      polyethylenimine and two cationic lipids as condensing agents, with transferrin
      on its surface for selective binding and enhanced cellular uptake. The optimized
      nitrogen to phosphate (N/P) ratio was 4 to achieve small particle size and high
      G3139 entrapment efficiency. The Tf-LPN-G3139 exhibited excellent colloidal
      stability during storage for at least 12 weeks and remained intact for 4 hours in
      nuclease-containing serum. The cellular uptake results showed extensive
      internalization of fluorescence-labelled G3139 in MV4-11 cells through Tf-LPN.
      Following transfection, Tf-LPN-G3139 at 1 uM ASO level induced 54% Bcl-2
      downregulation and >20-fold apoptosis compared to no treatment. When evaluated in
      mice bearing human xenograft AML tumors, Tf-LPN-G3139 suppressed tumor growth by
      ~60% at the end of treatment period, accompanied by remarkable pharmacological
      effect of Bcl-2 inhibition in tumor. In conclusion, Tf-LPN-G3139 is a promising
      nanoparticle system for ASO G3139 delivery to AML and warrants further
      investigations.

PMID- 27034926
TI  - Airway Management with Cervical Spine Immobilisation: A Comparison between the
      Macintosh Laryngoscope, Truview Evo2, and Totaltrack VLM Used by Novices--A
      Manikin Study.
AB  - Airway management in patients with suspected cervical spine injury plays an
      important role in the pathway of care of trauma patients. The aim of this study
      was to evaluate three different airway devices during intubation of a patient
      with reduced cervical spine mobility. Forty students of the third year of
      emergency medicine studies participated in the study (F = 26, M = 14). The time
      required to obtain a view of the entry to the larynx and successful ventilation
      time were recorded. Cormack-Lehane laryngoscopic view and damage to the incisors
      were also assessed. All three airway devices were used by each student (a novice)
      and they were randomly chosen. The mean time required to obtain the entry-to-the
      larynx view was the shortest for the Macintosh laryngoscope 13.4 s (+/-2.14).
      Truview Evo2 had the shortest successful ventilation time 35.7 s (+/-9.27). The
      best view of the entry to the larynx was obtained by the Totaltrack VLM device.
      The Truview Evo2 and Totaltrack VLM may be an alternative to the classic
      Macintosh laryngoscope for intubation of trauma patients with suspected injury to
      the cervical spine. The use of new devices enables achieving better laryngoscopic
      view as well as minimising incisor damage during intubation. 

PMID- 27034927
TI  - Effect of Motivation by "Instagram" on Adherence to Physical Activity among
      Female College Students.
AB  - OBJECTIVE: To investigate the efficacy of using "Instagram application" with a
      "home-exercise program" as a motivational stimulus in improving physical activity
      (PA) adherence levels among female college students. METHODS: Fifty-eight female
      undergraduate students with the mean age 20.3 +/- 0.96 years participated.
      Participants were divided into two groups: intervention and the control group;
      both the groups received an exercise program and the intervention group was
      additionally motivated by "Instagram." Adherence to PA was measured by using an
      adherence sheet. The Exercise Motivation Inventory (EMI-2) was used to assess the
      motivational factors. RESULTS: The most frequent motivational factors were
      extrinsic as assessed using the EMI-2. "Positive health" was the most frequent
      factor mentioned of the two types with 47% of the sample. The intervention group
      adhered with 17% more to the activity program compared to the control group.
      Moreover, 72% of the participants in the intervention and control groups found
      the activity program flexible enough to be performed at home; they agreed about
      its effectiveness on adherence (53%). CONCLUSIONS: The use of Instagram with the
      home exercise program as a motivational modality could be attractive and
      effective to reinforce adherence and maintain an appropriate PA level.

PMID- 27034928
TI  - An Efficient Approach to Screening Epigenome-Wide Data.
AB  - Screening cytosine-phosphate-guanine dinucleotide (CpG) DNA methylation sites in
      association with some covariate(s) is desired due to high dimensionality. We
      incorporate surrogate variable analyses (SVAs) into (ordinary or robust) linear
      regressions and utilize training and testing samples for nested validation to
      screen CpG sites. SVA is to account for variations in the methylation not
      explained by the specified covariate(s) and adjust for confounding effects. To
      make it easier to users, this screening method is built into a user-friendly R
      package, ttScreening, with efficient algorithms implemented. Various simulations
      were implemented to examine the robustness and sensitivity of the method compared
      to the classical approaches controlling for multiple testing: the false discovery
      rates-based (FDR-based) and the Bonferroni-based methods. The proposed approach
      in general performs better and has the potential to control both types I and II
      errors. We applied ttScreening to 383,998 CpG sites in association with maternal
      smoking, one of the leading factors for cancer risk. 

PMID- 27034929
TI  - Novel Technologies for Improved Treatment Outcome and Patient Safety in Cancer
      Radiotherapy.

PMID- 27034930
TI  - Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with
      Chronic Hyperglycemia and Chronic Kidney Disease.
AB  - Iodinated contrast (IC) is clinically used in diagnostic and interventional
      procedures, but its use can result in contrast-induced acute kidney injury (CI
      AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important
      predisposing factors to CI-AKI. The aim of this study was to investigate the
      impact of iodinated contrast on the renal function and hemodynamics in rats with
      chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided
      into six groups; Sham: control of chronic renal disease; Citrate: control of
      chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic
      Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6
      received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of
      IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated
      lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow;
      renal vascular resistance) were evaluated. Iodinated contrast significantly
      increased urinary NGAL and reduced inulin clearance, while the hemodynamics
      parameters showed changes in arterial blood pressure, renal blood flow, and renal
      vascular resistance in both CKD and CH groups. The results suggest that the
      iodinated contrast in risk factors models has important impact on renal function
      and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of
      CI-AKI. 

PMID- 27034931
TI  - Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from
      Gymnema sylvestre against Insulin Receptor Protein.
AB  - Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can
      affect the quality of life severely. Injectable insulin is currently being used
      to treat DM which is mainly associated with patient inconvenience. Small
      molecules that can act as insulin receptor (IR) agonist would be better
      alternatives to insulin injection. Herein, ten bioactive small compounds derived
      from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding
      affinity and ADMET properties using a combined approach of molecular docking
      study and computational pharmacokinetic elucidation. Designing structural
      analogues were also performed for the compounds associated with toxicity and less
      IR affinity. Among the ten parent compounds, six were found to have significant
      pharmacokinetic properties with considerable binding affinity towards IR while
      four compounds were associated with toxicity and less IR affinity. Among the
      forty structural analogues, four compounds demonstrated considerably increased
      binding affinity towards IR and less toxicity compared with parent compounds.
      Finally, molecular interaction analysis revealed that six parent compounds and
      four analogues interact with the active site amino acids of IR. So this study
      would be a way to identify new therapeutics and alternatives to insulin for
      diabetic patients. 

PMID- 27034932
TI  - Mobility in Old Age: Capacity Is Not Performance.
AB  - BACKGROUND: Outcomes of laboratory-based tests for mobility are often used to
      infer about older adults' performance in real life; however, it is unclear
      whether such association exists. We hypothesized that mobility capacity, as
      measured in the laboratory, and mobility performance, as measured in real life,
      would be poorly linked. METHODS: The sample consisted of 84 older adults (72.5 +/
      5.9 years). Capacity was assessed via the iTUG and standard gait parameters
      (stride length, stride velocity, and cadence). Performance was assessed in real
      life over a period of 6.95 +/- 1.99 days using smartphone technology to calculate
      following parameters: active and gait time, number of steps, life-space, mean
      action-range, and maximum action-range. Correlation analyses and stepwise
      multiple regression analyses were applied. RESULTS: All laboratory measures
      demonstrated significant associations with the real-life measures (between r =
      .229 and r = .461). The multiple regression analyses indicated that the
      laboratory measures accounted for a significant but very low proportion of
      variance (between 5% and 21%) in real-life measures. CONCLUSION: In older adults
      without mobility impairments, capacity-related measures of mobility bear little
      significance for predicting real-life performance. Hence, other factors play a
      role in how older people manage their daily-life mobility. This should be
      considered for diagnosis and treatment of mobility deficits in older people.

PMID- 27034933
TI  - Effectiveness of Percutaneous Balloon Mitral Valvuloplasty for Rheumatic Mitral
      Stenosis with Mild to Severe Mitral Regurgitation.
AB  - This study is designed to test whether percutaneous balloon mitral valvuloplasty
      (PBMV) is effective for rheumatic mitral stenosis in Chinese patients with
      moderate to severe mitral regurgitation. Fifty-six patients with rheumatic mitral
      valve stenosis were divided into the mild, moderate, and severe regurgitation
      groups. Cardiac ultrasonography was measured before and 1 to 2 days after PBMV.
      Following PBMV, the mitral orifice was enlarged, and the left atrial diameter was
      reduced in the 3 patient groups. The enlargement of the mitral orifice in the
      mild regurgitation group was greater than that observed in the moderate and
      severe regurgitation groups. The size of the regurgitation area increased in the
      mild regurgitation group and decreased in the moderate and severe regurgitation
      groups, with the decrease in the severe regurgitation group being greater than
      that in the moderate regurgitation group. Therefore, PBMV is effective for
      treating rheumatic mitral stenosis in Chinese patients with mild to severe mitral
      regurgitation. 

PMID- 27034934
TI  - Uremic Pruritus Is Not Associated with Endocannabinoid Receptor 1 Gene
      Polymorphisms.
AB  - Uremic pruritus (UP) is a frequent and bothersome symptom in hemodialysis
      patients. Its etiology is not fully understood and that is why there is no
      specific treatment. The endocannabinoid system plays a role in many pathological
      conditions. There is reliable evidence on the association between cannabinoid
      system and pruritus. In our study, we aimed to evaluate whether genetic
      variations in the endocannabinoid receptor 1 (CNR1) gene can affect UP. The
      rs12720071, rs806368, rs1049353, rs806381, rs10485170, rs6454674, and rs2023239
      polymorphisms of the CNR1 gene were genotyped in 159 hemodialysis patients and
      150 healthy controls using two multiplex polymerase chain reactions and the
      minisequencing technique. No statistically significant relationship was found in
      any of the evaluated genotypes between patients with and without UP, even after
      excluding patients with diabetes and dyslipidemia. There were no differences
      between patients with UP and the control group. However, in the group of all HD
      patients, a significantly higher incidence of GA genotype and lower incidence in
      GG genotype in the polymorphism rs806381s were revealed versus the control group
      (p = 0.04). It seems that polymorphisms of the CNR1 gene are not associated with
      uremic pruritus. 

PMID- 27034935
TI  - High Yielding Microbubble Production Method.
AB  - Microfluidic approaches to microbubble production are generally disadvantaged by
      low yield and high susceptibility to (micro)channel blockages. This paper
      presents an alternative method of producing microbubbles of 2.6 MUm mean diameter
      at concentrations in excess of 30 * 10(6) mL(-1). In this method, the nitrogen
      gas flowing inside the liquid jet is disintegrated into spray of microbubble when
      air surrounding this coflowing nitrogen gas-liquid jet passes through a 100 MUm
      orifice at high velocity. Resulting microbubble foam has the polydispersity index
      of 16%. Moreover, a ratio of mean microbubble diameter to channel width ratio was
      found to be less than 0.025, which substantially alleviates the occurrence of
      blockages during production. 

PMID- 27034936
TI  - Transcriptome Analysis of Ramie (Boehmeria nivea L. Gaud.) in Response to Ramie
      Moth (Cocytodes coerulea Guenee) Infestation.
AB  - The ramie moth Cocytodes coerulea Guenee (RM) is an economically important pest
      that seriously impairs the yield of ramie, an important natural fiber crop. The
      molecular mechanisms that underlie the ramie-pest interactions are unclear up to
      date. Therefore, a transcriptome profiling analysis would aid in understanding
      the ramie defense mechanisms against RM. In this study, we first constructed two
      cDNA libraries derived from RM-challenged (CH) and unchallenged (CK) ramie
      leaves. The subsequent sequencing of the CH and CK libraries yielded 40.2 and
      62.8 million reads, respectively. Furthermore, de novo assembling of these reads
      generated 26,759 and 29,988 unigenes, respectively. An integrated assembly of
      data from these two libraries resulted in 46,533 unigenes, with an average length
      of 845 bp per unigene. Among these genes, 24,327 (52.28%) were functionally
      annotated by predicted protein function. A comparative analysis of the CK and CH
      transcriptome profiles revealed 1,980 differentially expressed genes (DEGs), of
      which 750 were upregulated and 1,230 were downregulated. A quantitative real-time
      PCR (qRT-PCR) analysis of 13 random selected genes confirmed the gene expression
      patterns that were determined by Illumina sequencing. Among the DEGs, the
      expression patterns of transcription factors, protease inhibitors, and
      antioxidant enzymes were studied. Overall, these results provide useful insights
      into the defense mechanism of ramie against RM. 

PMID- 27034937
TI  - Does Subacromial Osteolysis Affect Shoulder Function after Clavicle Hook Plating?
AB  - PURPOSE: To evaluate whether subacromial osteolysis, one of the major
      complications of the clavicle hook plate procedure, affects shoulder function.
      METHODS: We had performed a retrospective study of 72 patients diagnosed with a
      Neer II lateral clavicle fracture or Degree-III acromioclavicular joint
      dislocation in our hospital from July 2012 to December 2013. All these patients
      had undergone surgery with clavicle hook plate and were divided into two groups
      based on the occurrence of subacromial osteolysis. By using the Constant-Murley
      at the first follow-up visit after plates removal, we evaluated patients'
      shoulder function to judge if it has been affected by subacromial osteolysis.
      RESULTS: We have analyzed clinical data for these 72 patients, which shows that
      there is no significant difference between group A (39 patients) and group B (33
      patients) in age, gender, injury types or side, and shoulder function (the
      Constant-Murley scores are 93.38 +/- 3.56 versus 94.24 +/- 3.60, P > 0.05).
      CONCLUSION: The occurrence of subacromial osteolysis is not rare, and also it
      does not significantly affect shoulder function.

PMID- 27034938
TI  - Thyroid Remnant Estimation by Diagnostic Dose (131)I Scintigraphy or (99m)TcO4(-)
      Scintigraphy after Thyroidectomy: A Comparison with Therapeutic Dose (131)I
      Imaging.
AB  - In this clinical study, we have compared routine diagnostic dose (131)I scan and
      (99m)TcO4(-) thyroid scintigraphy with therapeutic dose (131)I imaging for
      accurate thyroid remnant estimation after total thyroidectomy. We conducted a
      retrospective review of the patients undergoing total thyroidectomy for
      differentiated thyroid carcinoma (DTC) and subsequently receiving radioactive
      iodine (RAI) treatment to ablate remnant thyroid tissue. All patients had
      therapeutic dose RAI whole body scan, which was compared with that of diagnostic
      dose RAI, (99m)TcO4(-) thyroid scan, and ultrasound examination. We concluded
      that therapeutic dose RAI scan reveals some extent thyroid remnant in all DTC
      patients following total thyroidectomy. Diagnostic RAI scan is much superior to
      ultrasound and (99m)TcO4(-) thyroid scan for the postoperative estimation of
      thyroid remnant. Ultrasound and (99m)TcO4(-) thyroid scan provide little
      information for thyroid remnant estimation and, therefore, would not replace
      diagnostic RAI scan.

PMID- 27034939
TI  - Identification and Assessment of the Potential Allergenicity of 7S Vicilins in
      Olive (Olea europaea L.) Seeds.
AB  - Olive seeds, which are a raw material of interest, have been reported to contain
      11S seed storage proteins (SSPs). However, the presence of SSPs such as 7S
      vicilins has not been studied. In this study, following a search in the olive
      seed transcriptome, 58 sequences corresponding to 7S vicilins were retrieved. A
      partial sequence was amplified by PCR from olive seed cDNA and subjected to
      phylogenetic analysis with other sequences. Structural analysis showed that olive
      7S vicilin contains 9 alpha-helixes and 22 beta-sheets. Additionally, 3D
      structural analysis displayed good superimposition with vicilin models generated
      from Pistacia and Sesamum. In order to assess potential allergenicity, T and B
      epitopes present in these proteins were identified by bioinformatic approaches.
      Different motifs were observed among the species, as well as some species
      specific motifs. Finally, expression analysis of vicilins was carried out in
      protein extracts obtained from seeds of different species, including the olive.
      Noticeable bands were observed for all species in the 15-75 kDa MW interval,
      which were compatible with vicilins. The reactivity of the extracts to sera from
      patients allergic to nuts was also analysed. The findings with regard to the
      potential use of olive seed as food are discussed. 

PMID- 27034940
TI  - Laser Scanning In Vivo Confocal Microscopy of Clear Grafts after Penetrating
      Keratoplasty.
AB  - PURPOSE: To evaluate the changes of keratocytes and dendritic cells in the
      central clear graft by laser scanning in vivo confocal microscopy after
      penetrating keratoplasty (PK). METHODS: Thirty adult subjects receiving PK at
      Shandong Eye Institute and with clear grafts and no sign of immune rejection
      after surgery were recruited into this study, and 10 healthy adults were
      controls. The keratocytes and dendritic cells in the central graft were evaluated
      by laser scanning confocal microscopy, as well as epithelium cells, keratocytes,
      corneal endothelium cells, and corneal nerves (especially subepithelial plexus
      nerves). RESULTS: Median density of subepithelial plexus nerves, keratocyte
      density in each layer of the stroma, and density of corneal endothelium cells
      were all lower in clear grafts than in controls. The dendritic cells of five
      (16.7%) patients were active in Bowman's membrane and stromal membrane of the
      graft after PK. CONCLUSIONS: Activated dendritic cells and Langerhans cells could
      be detected in some of the clear grafts, which indicated that the subclinical
      stress of immune reaction took part in the chronic injury of the clear graft
      after PK, even when there was no clinical rejection episode.

PMID- 27034941
TI  - Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End
      Products.
AB  - Diabetic nephropathy (DN) caused by advanced glycation end products (AGEs) may be
      associated with lipid accumulation in the kidneys. This study was designed to
      investigate whether Nepsilon-(carboxymethyl) lysine (CML, a member of the AGEs
      family) increases lipid accumulation in a human renal tubular epithelial cell
      line (HK-2) via increasing cholesterol synthesis and uptake and reducing
      cholesterol efflux through endoplasmic reticulum stress (ERS). Our results showed
      that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol
      regulatory element-binding protein 2 (SREBP-2) and liver X receptor (LXR),
      followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG
      CoAR) mediated cholesterol synthesis and low density lipoprotein receptor (LDLr)
      mediated cholesterol uptake and a reduction in ATP-binding cassette transporter
      A1 (ABCA1) mediated cholesterol efflux, ultimately causing lipid accumulation in
      HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which
      suggests that CML causes lipid accumulation in renal tubule cells through ERS and
      that the inhibition of ERS is a potential novel approach to treating CML-induced
      renal tubular foam cell formation. 

PMID- 27034942
TI  - Leaf Proteome Analysis Reveals Prospective Drought and Heat Stress Response
      Mechanisms in Soybean.
AB  - Drought and heat are among the major abiotic stresses that affect soybean crops
      worldwide. During the current investigation, the effect of drought, heat, and
      drought plus heat stresses was compared in the leaves of two soybean varieties,
      Surge and Davison, combining 2D-DIGE proteomic data with physiology and
      biochemical analyses. We demonstrated how 25 differentially expressed
      photosynthesis-related proteins affect RuBisCO regulation, electron transport,
      Calvin cycle, and carbon fixation during drought and heat stress. We also
      observed higher abundance of heat stress-induced EF-Tu protein in Surge. It is
      possible that EF-Tu might have activated heat tolerance mechanisms in the
      soybean. Higher level expressions of heat shock-related protein seem to be
      regulating the heat tolerance mechanisms. This study identifies the differential
      expression of various abiotic stress-responsive proteins that regulate various
      molecular processes and signaling cascades. One inevitable outcome from the
      biochemical and proteomics assays of this study is that increase of ROS levels
      during drought stress does not show significant changes at the phenotypic level
      in Davison and this seems to be due to a higher amount of carbonic anhydrase
      accumulation in the cell which aids the cell to become more resistant to
      cytotoxic concentrations of H2O2. 

PMID- 27034943
TI  - The Significance of Ultrasound in Determining Whether SHPT Patients Are Sensitive
      to Calcitriol Treatment.
AB  - This study was to explore the significance of ultrasound in determining whether
      the patients with secondary hyperparathyroidism (SHPT) are sensitive to
      calcitriol treatment. According to the decrease value of parathyroid hormone
      (PTH), 42 SHPT patients were divided into two groups: drug susceptible group and
      drug insusceptible group. These 42 SHPT patients' ultrasound images were
      retrospectively analyzed. The morphology, size, number, blood flow, elastic
      modulus, and perfusion of the parathyroid glands were correlated with drug
      therapeutic outcome (oral calcitriol). Most SHPT patients with drug susceptible
      showed volume <438.50 mm(3) and number <=2, with 0-1 structural and vascular
      patterns, associated with Relative Maximum Intensity (RIMAX) <1.59 and elastic
      modulus <18.8 kPa, whereas most SHPT patients with drug insusceptible showed
      volume >=438.50 mm(3) and number >=3, with 2-3 structural and vascular patterns,
      associated with Relative Maximum Intensity (RIMAX) >=1.59 and elastic modulus
      >=18.8 kPa. Therefore, ultrasonography in SHPT allows an accurate definition of
      the morphology, size, number, blood flow, elastic modulus, and perfusion of the
      parathyroid glands and is useful in determining whether SHPT patients are
      sensitive to calcitriol treatment. 

PMID- 27034944
TI  - Tsetse Flies (Glossina) as Vectors of Human African Trypanosomiasis: A Review.
AB  - Human African Trypanosomiasis (HAT) transmitted by the tsetse fly continues to be
      a public health issue, despite more than a century of research. There are two
      types of the disease, the chronic gambiense and the acute rhodesiense-HAT. Fly
      abundance and distribution have been affected by changes in land-use patterns and
      climate. However, disease transmission still continues. Here, we review some
      aspects of HAT ecoepidemiology in the context of altered infestation patterns and
      maintenance of the transmission cycle as well as emerging options in disease and
      vector control. 

PMID- 27034945
TI  - Efficacy Comparison of Tenofovir and Entecavir in HBeAg-Positive Chronic
      Hepatitis B Patients with High HBV DNA.
AB  - OBJECTIVES: To compare entecavir (ETV) and tenofovir disoproxil fumarate (TDF)
      effects in chronic hepatitis B (CHB) patients with high HBV DNA. METHOD: 96
      patients treated initially with tenofovir (TDF group) or entecavir (ETV group)
      were included in this retrospective study. The following parameters were
      assessed: HBeAg and hepatitis B e antibody (anti-HBe) status, serum alanine
      aminotransferase (ALT), and HBV-DNA levels at weeks 4, 12, 24, 36, 48, 60, 72,
      and 96; time to ALT normalization, undetectable HBV-DNA levels, and HBeAg
      seroconversion; total duration of follow-up and adverse reactions. RESULTS: The
      patients included 66 (69%) and 30 (31%) individuals administered ETV and TDF,
      respectively, comprising 75% males. They were 35.1 +/- 4.5 and 33.7 +/- 4.6 years
      old in ETV and TDF groups, respectively. At 36 weeks, the response rate was
      significantly higher in the TDF group than in ETV treated patients (90% versus
      69.7%, p = 0.03). At 48 weeks, less patients administered ETV showed undetectable
      HBV-DNA levels compared with the TDF group (86.4% versus 96.7%), a non
      statistically significant difference (p = 0.13). Only 1 ETV treated patient
      developed virological breakthrough at 48-96 w. No adverse reactions were found.
      CONCLUSION: ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA
      replication in HBeAg-positive CHB patients with high HBV DNA.

PMID- 27034946
TI  - Cross-Sectional Nakagami Images in Passive Stretches Reveal Damage of Injured
      Muscles.
AB  - Muscle strain is still awanting a noninvasive quantitatively diagnosis tool. High
      frequency ultrasound (HFU) improves image resolution for monitoring changes of
      tissue structures, but the biomechanical factors may influence ultrasonography
      during injury detection. We aim to illustrate the ultrasonic parameters to
      present the histological damage of overstretched muscle with the consideration of
      biomechanical factors. Gastrocnemius muscles from mice were assembled and ex vivo
      passive stretching was performed before or after injury. After injury, the muscle
      significantly decreased mechanical strength. Ultrasonic images were obtained by
      HFU at different deformations to scan in cross and longitudinal orientations of
      muscle. The ultrasonography was quantified by echogenicity and Nakagami
      parameters (NP) for structural evaluation and correlated with histological
      results. The injured muscle at its original length exhibited decreased
      echogenicity and NP from HFU images. Cross-sectional ultrasonography revealed a
      loss of correlation between NP and passive muscle stretching that suggested a
      special scatterer pattern in the cross section of injured muscle. The
      independence of NP during passive stretching of injured muscle was confirmed by
      histological findings in ruptured collagen fibers, decreased muscle density, and
      increased intermuscular fiber space. Thus, HFU analysis of NP in cross section
      represents muscle injury that may benefit the clinical diagnosis. 

PMID- 27034947
TI  - Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A
      Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity.
AB  - Posture control during a dual-task involves changing the distribution of
      attention resources between the cognitive and motor tasks and involves the
      frontal cortex working memory (WM). The present study aimed to better understand
      the impact of frontal lobe activity and WM capacity in postural control during a
      dual-task. High and low WM-span groups were compared using their reading span
      test scores. High and low WM capacity were compared based on cognitive and
      balance performance and hemoglobin oxygenation (oxyHb) levels during standing
      during single (S-S), standing during dual (S-D), one leg standing during single
      (O-S), and one leg standing during dual (O-D) tasks. For sway pass length,
      significant difference in only the O-D task was observed between both groups.
      oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex
      and supplementary motor area in the high-span group during a dual-task.
      Therefore, WM capacity influenced the allocation of attentional resources and
      motor performance. 

PMID- 27034948
TI  - Rhabdomyolysis following Cardiac Surgery: A Prospective, Descriptive, Single
      Center Study.
AB  - PURPOSE: Rhabdomyolysis (RML) following cardiac surgery and its relationship with
      acute kidney injury (AKI) require investigation. PATIENTS AND METHODS: All
      patients undergoing cardiac surgery in our hospital were enrolled in this
      prospective study during a 1-year period. To investigate the occurrence of RML
      and its association with AKI, all patients in the study underwent serial
      assessment of serum creatine kinase (CK) and myoglobin levels. Serial renal
      function, prior statin treatment, and outcome variables were recorded. RESULTS:
      In total, 201 patients were included in the study: 185 men and 16 women with a
      mean age of 52.0 +/- 12.4 years. According to the presence of RML (CK of >=2,500
      U/L), the patients were divided into Group I (RML present in 17 patients) and
      Group II (RML absent in 184 patients). Seven patients in Group I had AKI (41%)
      where 34 patients in group II had AKI (18.4%), P = 0.025. We observed a
      significantly longer duration of ventilation, length of stay in the ICU, and
      hospitalization in Group I (P < 0.001 for all observations). CONCLUSIONS: An
      early elevation of serum CK above 2500 U/L postoperatively in high-risk cardiac
      surgery could be used to diagnose RML that may predict the concomitance of early
      AKI.

PMID- 27034949
TI  - A Multifeatures Fusion and Discrete Firefly Optimization Method for Prediction of
      Protein Tyrosine Sulfation Residues.
AB  - Tyrosine sulfation is one of the ubiquitous protein posttranslational
      modifications, where some sulfate groups are added to the tyrosine residues. It
      plays significant roles in various physiological processes in eukaryotic cells.
      To explore the molecular mechanism of tyrosine sulfation, one of the
      prerequisites is to correctly identify possible protein tyrosine sulfation
      residues. In this paper, a novel method was presented to predict protein tyrosine
      sulfation residues from primary sequences. By means of informative feature
      construction and elaborate feature selection and parameter optimization scheme,
      the proposed predictor achieved promising results and outperformed many other
      state-of-the-art predictors. Using the optimal features subset, the proposed
      method achieved mean MCC of 94.41% on the benchmark dataset, and a MCC of 90.09%
      on the independent dataset. The experimental performance indicated that our new
      proposed method could be effective in identifying the important protein
      posttranslational modifications and the feature selection scheme would be
      powerful in protein functional residues prediction research fields. 

PMID- 27034950
TI  - N-(11)C-Methyl-Dopamine PET Imaging of Sympathetic Nerve Injury in a Swine Model
      of Acute Myocardial Ischemia: A Comparison with (13)N-Ammonia PET.
AB  - OBJECTIVE: Using a swine model of acute myocardial ischemia, we sought to
      validate N-(11)C-methyl-dopamine ((11)C-MDA) as an agent capable of imaging
      cardiac sympathetic nerve injury. METHODS: Acute myocardial ischemia was
      surgically generated in Chinese minipigs. ECG and serum enzyme levels were used
      to detect the presence of myocardial ischemia. Paired (11)C-MDA PET and (13)N
      ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after
      surgery to relate cardiac sympathetic nerve injury to blood perfusion. RESULTS:
      Seven survived the surgical procedure. The ECG-ST segment was depressed, and
      levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as
      the defect volume. Both before and immediately after surgery, the images obtained
      with (11)C-MDA and (13)N-ammonia were similar. At 1 to 6 months after surgery,
      however, (11)C-MDA postsurgical left ventricular myocardial defect volume was
      significantly greater compared to (13)N-ammonia. CONCLUSIONS: In the Chinese
      minipig model of acute myocardial ischemia, the extent of the myocardial defect
      as visualized by (11)C-MDA is much greater than would be suggested by blood
      perfusion images, and the recovery from myocardial sympathetic nerve injury is
      much slower than the restoration of blood perfusion. (11)C-MDA PET may provide
      additional biological information during recovery from ischemic heart disease.

PMID- 27034951
TI  - Development of High-Field Permanent Magnetic Circuits for NMRI/MRI and Imaging on
      Mice.
AB  - The high-field permanent magnetic circuits of 1.2 T and 1.5 T with novel magnetic
      focusing and curved-surface correction are developed. The permanent magnetic
      circuit comprises a magnetic yoke, main magnetic steel, nonspherical curved
      surface magnetic poles, plugging magnetic steel, and side magnetic steel. In this
      work, a novel shimming method is proposed for the effective correction of base
      magnetic field (B 0) inhomogeneities, which is based on passive shimming on the
      telescope aspheric cutting, grinding, and fine processing technology of the
      nonspherical curved-surface magnetic poles and active shimming adding higher
      order gradient coils. Meanwhile, the magnetic resonance imaging dedicated alloy
      with high-saturation magnetic field induction intensity and high electrical
      resistivity is developed, and nonspherical curved-surface magnetic poles which
      are made of the dedicated alloy have very good anti-eddy-current effect. In
      addition, the large temperature coefficient problem of permanent magnet can be
      effectively controlled by using a high quality temperature controller and
      deuterium external locking technique. Combining our patents such as gradient
      coil, RF coil, and integration computer software, two kinds of small animal Micro
      MRI instruments are developed, by which the high quality MRI images of mice were
      obtained. 

PMID- 27034952
TI  - Analysis and Classification of Stride Patterns Associated with Children
      Development Using Gait Signal Dynamics Parameters and Ensemble Learning
      Algorithms.
AB  - Measuring stride variability and dynamics in children is useful for the
      quantitative study of gait maturation and neuromotor development in childhood and
      adolescence. In this paper, we computed the sample entropy (SampEn) and average
      stride interval (ASI) parameters to quantify the stride series of 50 gender
      matched children participants in three age groups. We also normalized the SampEn
      and ASI values by leg length and body mass for each participant, respectively.
      Results show that the original and normalized SampEn values consistently decrease
      over the significance level of the Mann-Whitney U test (p < 0.01) in children of
      3-14 years old, which indicates the stride irregularity has been significantly
      ameliorated with the body growth. The original and normalized ASI values are also
      significantly changing when comparing between any two groups of young (aged 3-5
      years), middle (aged 6-8 years), and elder (aged 10-14 years) children. Such
      results suggest that healthy children may better modulate their gait cadence
      rhythm with the development of their musculoskeletal and neurological systems. In
      addition, the AdaBoost.M2 and Bagging algorithms were used to effectively
      distinguish the children's gait patterns. These ensemble learning algorithms both
      provided excellent gait classification results in terms of overall accuracy
      (>=90%), recall (>=0.8), and precision (>=0.8077). 

PMID- 27034953
TI  - A Virtual Reality-Cycling Training System for Lower Limb Balance Improvement.
AB  - Stroke survivors might lose their walking and balancing abilities, but many
      studies pointed out that cycling is an effective means for lower limb
      rehabilitation. However, during cycle training, the unaffected limb tends to
      compensate for the affected one, which resulted in suboptimal rehabilitation. To
      address this issue, we present a Virtual Reality-Cycling Training System (VRCTS),
      which senses the cycling force and speed in real-time, analyzes the acquired data
      to produce feedback to patients with a controllable VR car in a VR rehabilitation
      program, and thus specifically trains the affected side. The aim of the study was
      to verify the functionality of the VRCTS and to verify the results from the ten
      stroke patients participants and to compare the result of Asymmetry Ratio Index
      (ARI) between the experimental group and the control group, after their training,
      by using the bilateral pedal force and force plate to determine any training
      effect. The results showed that after the VRCTS training in bilateral pedal force
      it had improved by 0.22 (p = 0.046) and in force plate the stand balance has also
      improved by 0.29 (p = 0.031); thus both methods show the significant difference. 

PMID- 27034954
TI  - Study of Valproic Acid-Enhanced Hepatocyte Steatosis.
AB  - Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However,
      several side effects, including weight gain and fatty liver, have been reported
      in patients following VPA treatment. In this study, we explored the molecular
      mechanisms of VPA-induced hepatic steatosis using FL83B cell line-based in vitro
      model. Using fluorescent lipid staining technique, we found that VPA enhanced
      oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in
      hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG)
      synthesis, and lipid droplet formation. Real-time PCR results showed that,
      following VPA treatment, the expression levels of genes encoding cluster of
      differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1
      (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were
      increased, that of carnitine palmitoyltransferase I a (Cpt1a) was not affected,
      and those of acetyl-Co A carboxylase alpha (Acca) and fatty acid synthase (Fasn)
      were decreased. Furthermore, using immunofluorescence staining and flow cytometry
      analyses, we found that VPA also induced peroxisome proliferator-activated
      receptor gamma (PPARgamma) nuclear translocation and increased levels of cell
      surface CD36. Based on these results, we propose that VPA may enhance OLA-induced
      hepatocyte steatosis through the upregulation of PPARgamma- and CD36-dependent
      lipid uptake, TAG synthesis, and lipid droplet formation. 

PMID- 27034955
TI  - Genome-Wide Transcriptome Analysis of Cadmium Stress in Rice.
AB  - Rice growth is severely affected by toxic concentrations of the nonessential
      heavy metal cadmium (Cd). To elucidate the molecular basis of the response to Cd
      stress, we performed mRNA sequencing of rice following our previous study on
      exposure to high concentrations of Cd (Oono et al., 2014). In this study, rice
      plants were hydroponically treated with low concentrations of Cd and
      approximately 211 million sequence reads were mapped onto the IRGSP-1.0 reference
      rice genome sequence. Many genes, including some identified under high Cd
      concentration exposure in our previous study, were found to be responsive to low
      Cd exposure, with an average of about 11,000 transcripts from each condition.
      However, genes expressed constitutively across the developmental course responded
      only slightly to low Cd concentrations, in contrast to their clear response to
      high Cd concentration, which causes fatal damage to rice seedlings according to
      phenotypic changes. The expression of metal ion transporter genes tended to
      correlate with Cd concentration, suggesting the potential of the RNA-Seq strategy
      to reveal novel Cd-responsive transporters by analyzing gene expression under
      different Cd concentrations. This study could help to develop novel strategies
      for improving tolerance to Cd exposure in rice and other cereal crops. 

PMID- 27034956
TI  - Periostin Facilitates the Epithelial-Mesenchymal Transition of Endometrial
      Epithelial Cells through ILK-Akt Signaling Pathway.
AB  - Although periostin was confirmed to facilitate the pathogenesis of endometriosis
      by enhancing the migration, invasion, and adhesion of human endometrial stromal
      cells (ESCs), its effect on the endometrial epithelial cells (EECs) is still
      unknown. The current study aimed to determine whether periostin enhanced the
      epithelial-mesenchymal transition (EMT) of EECs. EECs were isolated from 12 women
      with endometriosis. The migration and invasion abilities of EECs were evaluated
      by transwell assays. Expressions of proteins were detected by western blot. After
      treatment with periostin, the migration and invasion abilities of EECs were
      enhanced. Additionally, E-cadherin and keratin were downregulated while N
      cadherin and vimentin were upregulated in EECs. Simultaneously, levels of ILK, p
      Akt, slug, and Zeb1 were all upregulated in EECs. After silencing the expression
      of ILK in EECs, levels of p-Akt, slug, Zeb1, N-cadherin, and vimentin were
      downregulated while E-cadherin and keratin were upregulated. Although periostin
      weakened the above effects in EECs after silencing the expression of ILK, it
      failed to induce the EMT of EECs. Thus, periostin enhanced invasion and migration
      abilities of EECs and facilitated the EMT of EECs through ILK-Akt signaling
      pathway. Playing a pivotal role in the pathogenesis of endometriosis, periostin
      may be a new clinical therapy target for endometriosis. 

PMID- 27034957
TI  - Usability Pitfalls of Diabetes mHealth Apps for the Elderly.
AB  - Diabetes mellitus has high prevalence in the ageing population and is often
      accompanied by other comorbidities, such as Alzheimer's disease, and general
      disabilities, such as poor eyesight. These comorbidities have redefined ways in
      which patients use mHealth apps, including diabetes apps. The latter have proven
      benefits for monitoring blood glucose levels and insulin tracking in the general
      population. In this paper, we analyse a diabetes monitoring app DeStress
      Assistant (DeSA), which was developed as a part of an EU project and tested in a
      hospital setting. Due to the increasing number of older adults, we wanted to
      ensure the app was suitable for that demographic. Based on a number of supervised
      tests, we show that the app, which was developed with the help of workshops and
      feedback from tech-savvy patients and clinicians, is difficult to use by elderly
      users. We demonstrate that with a small number of changes it is possible to raise
      the usability of the app in a number of categories. We summarise the lessons
      learned in the discussion. Our findings demonstrate that special care needs to be
      taken when developing mHealth apps for the elderly population.

PMID- 27034958
TI  - n-3 Polyunsaturated Fatty Acid Supplementation Has No Effect on Postprandial
      Triglyceride-Rich Lipoprotein Kinetics in Men with Type 2 Diabetes.
AB  - Dietary n-3 polyunsaturated fatty acids (PUFAs) have been proposed to modulate
      plasma lipids, lipoprotein metabolism, and inflammatory state and to reduce
      triglyceride (TG) concentrations. The present double-blind, randomized, placebo
      controlled, crossover study investigated the effects of n-3 PUFA supplementation
      at 3 g/d for 8 weeks on the intravascular kinetics of intestinally derived
      apolipoprotein (apo) B-48-containing lipoproteins in 10 men with type 2 diabetes.
      In vivo kinetics of the TG-rich lipoprotein (TRL) apoB-48 and VLDL apoB-100 were
      assessed using a primed-constant infusion of L-[5,5,5-D3] leucine for 12 hours in
      a fed state. Compared with the placebo, n-3 PUFA supplementation significantly
      reduced fasting TG concentrations by -9.7% (P = 0.05) but also significantly
      increased plasma levels of cholesterol (C) (+6.0%, P = 0.05), LDL-C (+12.2%, P =
      0.04), and HDL-C (+8.4, P = 0.007). n-3 PUFA supplementation had no significant
      impact on postprandial TRL apoB-48 and VLDL apoB-100 levels or on the production
      or catabolic rates of these lipoproteins. These data indicate that 8-week
      supplementation with n-3 PUFAs in men with type 2 diabetes has no beneficial
      effect on TRL apoB-48 and VLDL apoB-100 levels or kinetics.

PMID- 27034959
TI  - Lactic Acidosis in Diabetic Population: Is Metformin Implicated? Results of a
      Matched Case-Control Study Performed on the Type 2 Diabetes Population of
      Grenoble Hospital University.
AB  - INTRODUCTION: To evaluate the strength of association between lactic acidosis
      (LA) and well-recognized risk factors for LA, particularly the weight of
      metformin. METHODS: This study is a matched case-control analysis concerning the
      type 2 diabetes population from Grenoble Hospital University. Cases of LA were
      defined biologically with pH < 7.35 and lactates > 5 mmol/L. They were matched to
      2 controls defined as type 2 diabetic inpatients who did not present a LA during
      the study period. We performed a conditional logistic regression. RESULTS: We
      included 302 cases and 604 controls; mean age was 69.5 years (SD 11.93).
      Intercurrent diseases were significantly associated with LA. Chronic medical
      conditions had a minor impact on LA incidence, except hepatocellular dysfunction.
      Metformin was significantly associated with a higher LA probability in case of
      acute kidney injury (AKI) (OR = 1.79; p value = 0.020) but not in patients
      without AKI. DISCUSSION AND CONCLUSIONS: According to this study, metformin,
      compared to acute medical conditions, seemed not to be associated with LA in
      patients with type 2 diabetes; however in case of AKI, metformin may be
      associated with LA.

PMID- 27034960
TI  - The Adenosinergic System in Diabetic Retinopathy.
AB  - The neurodegenerative and inflammatory environment that is prevalent in the
      diabetic eye is a key player in the development and progression of diabetic
      retinopathy. The adenosinergic system is widely regarded as a significant
      modulator of neurotransmission and the inflammatory response, through the actions
      of the four types of adenosine receptors (A1R, A2AR, A2BR, and A3R), and thus
      could be revealed as a potential player in the events unfolding in the early
      stages of diabetic retinopathy. Herein, we review the studies that explore the
      impact of diabetic conditions on the retinal adenosinergic system, as well as the
      role of the said system in ameliorating or exacerbating those conditions. The
      experimental results described suggest that this system is heavily affected by
      diabetic conditions and that the modulation of its components could reveal
      potential therapeutic targets for the treatment of diabetic retinopathy,
      particularly in the early stages of the disease.

PMID- 27034961
TI  - Studies on the Antidiabetic and Antinephritic Activities of Paecilomyces hepiali
      Water Extract in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.
AB  - Paecilomyces hepiali is a fungus widely used in Asian countries for various
      potential pharmacological activities. The present study aims to evaluate the
      antidiabetic and antinephritic effects of the Paecilomyces hepiali mycelium water
      extract (PHC) in diabetic rat, which is established by eight-week high-fat diet
      administration followed by one-week tail intravenous injection of 25 mg/kg
      streptozotocin (STZ). After four-week 0.12 g/kg metformin and PHC at doses of
      0.08, 0.4, and 2.0 g/kg treatment, an increment of body weight, a decrement of
      plasma glucose, low levels of total cholesterol, and low density lipoprotein
      cholesterol in diabetic rats were observed. PHC promotes glucose metabolism by
      enhancing insulin, pyruvate kinase activity, and increasing the synthesis of
      glycogen. PHC normalized the disturbed levels of superoxide dismutase, methane
      dicarboxylic aldehyde, and glutathione peroxidase in kidney. The inhibitory
      effects on the levels of interleukin-2, interleukin-6, interleukin-10, and tumor
      necrosis factor-alpha in serum and kidney revealed the protection of PHC against
      diabetic nephropathy. Compared with nontreated diabetic rats, four-week PHC
      treatment resulted in a decrement on nuclear factor kappa B expression in kidney.
      These results show that Paecilomyces hepiali possesses antidiabetic and
      antinephritic effects which are related to the modulation of nuclear factor kappa
      B activity.

PMID- 27034962
TI  - Diabetic Microangiopathy Is an Independent Predictor of Incident Diabetic Foot
      Ulcer.
AB  - AIM: To determine the diabetic foot ulcer incidence and examine its association
      with microangiopathy complications, including diabetic retinopathy (DR) and
      albuminuria (Alb), in type 2 diabetes patients. METHODS: This was a retrospective
      cohort study of 1,305 patients with type 2 diabetes who were assigned to the
      following groups: Category 1, normoalbuminuria without DR (n = 712); Category 2,
      Alb without DR (n = 195); Category 3, normoalbuminuria with DR (n = 185); and
      Category 4, Alb with DR (n = 213). Cox proportional hazard models were used to
      compare the risks of developing diabetic foot ulcers across the categories.
      RESULTS: During 14,249 person-years of follow-up, 50 subjects developed diabetic
      foot ulcers, with incidence rates of 1.6/1,000, 1.5/1,000, 3.4/1,000, and
      12.5/1,000 person-years in Categories 1, 2, 3, and 4, respectively. After
      adjusting for the presence of diabetic neuropathy and macroangiopathy, the hazard
      ratios and 95% confidence intervals (CIs) for the risk of diabetic foot ulcer
      development were 0.66 (95% CI, 0.18-2.36), 1.72 (95% CI, 0.67-4.42), and 3.17
      (95% CI, 1.52-6.61) in Categories 2, 3, and 4, respectively, compared with
      Category 1. CONCLUSION: The presence of DR and Alb significantly increases the
      risk of diabetic foot ulcer development.

PMID- 27034963
TI  - Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction
      Function and Phosphorylation in the Mouse Heart.
AB  - Diabetic patients develop larger myocardial infarctions and have an increased
      risk of death following a heart attack. The poor response to myocardial injury in
      the diabetic heart is likely related to the many metabolic derangements from
      diabetes that create a poor substrate in general for wound healing, response to
      injury and infection. Studies in rodents have implicated a role for the gap
      junction protein connexin 43 (Cx43) in regulating the injury response in diabetic
      skin wounds. In this study, we sought to determine whether diabetes alters Cx43
      molecular interactions or intracellular communication in the cryoinjured STZ type
      I diabetic mouse heart. We found that epicardial cryoinjury size is increased in
      diabetic mice and this increase is prevented by preinjury insulin administration.
      Consistent with these findings, we found that intercellular coupling via gap
      junctions is decreased after insulin administration in diabetic and nondiabetic
      mice. This decrease in coupling is associated with a concomitant increase in
      phosphorylation of Cx43 at serine 368, a residue known to decrease channel
      conductance. Taken together, our results suggest that insulin regulates both gap
      junction-mediated intercellular communication and injury propagation in the mouse
      heart.

PMID- 27034964
TI  - Differential Use of Human Neutrophil Fcgamma Receptors for Inducing Neutrophil
      Extracellular Trap Formation.
AB  - Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from
      the circulation to sites of infection, where they are responsible for
      antimicrobial functions. PMN use phagocytosis, degranulation, and formation of
      neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed
      of chromatin and neutrophil-granule proteins. Several pathogens, including
      bacteria, fungi, and parasites, and also some pharmacological stimuli such as
      phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen
      antibody complexes are also capable of inducing NET formation. However the
      particular Fcgamma receptor involved in triggering this function is a matter of
      controversy. In order to provide some insight into what Fcgamma receptor is
      responsible for NET formation, each of the two human Fcgamma receptors was
      stimulated individually by specific monoclonal antibodies and NET formation was
      evaluated. FcgammaRIIa cross-linking did not promote NET formation. Cross-linking
      other receptors such as integrins also did not promote NET formation. In contrast
      FcgammaRIIIb cross-linking induced NET formation similarly to PMA stimulation.
      NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data
      show that cross-linking FcgammaRIIIb is responsible for NET formation by the
      human neutrophil. 

PMID- 27034966
TI  - Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and
      Semiquantitation.
AB  - Therapeutic proteins and peptides have potential to elicit immune responses
      resulting in anti-drug antibodies that can pose problems for both patient safety
      and product efficacy. During drug development immunogenicity is usually examined
      by risk-based approach along with specific strategies for developing "fit-for
      purpose" bioanalytical approaches. Enzyme-linked immunosorbent assays and
      electrochemiluminescence immunoassays are the most widely used platform for ADA
      detection due to their high sensitivity and throughput. During the past decade,
      LC/MS has emerged as a promising technology for quantitation of biotherapeutics
      and protein biomarkers in biological matrices, mainly owing to its high
      specificity, selectivity, multiplexing, and wide dynamic range. In fully taking
      these advantages, we describe here an immunocapture-LC/MS methodology for
      simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA
      and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab,
      immobilized on streptavidin magnetic beads, and separated from human plasma by a
      magnet. ADA is then released from the beads and subjected to trypsin digestion
      followed by LC/MS detection of specific universal peptides for each ADA isotype.
      The LC/MS data are analyzed using cut-point and calibration curve. The proof-of
      concept of this methodology is demonstrated by detecting preexisting ADA in human
      plasma. 

PMID- 27034967
TI  - Knowledge, Awareness and Behavior: HIV/AIDS and Disasters.
AB  - : African Americans are the most affected by HIV/AIDS. Both males and females
      continue to be disproportionately affected by HIV/AIDS. They are often drug users
      or participate in street/drug subculture. Recent weather disasters have required
      identification of knowledge, beliefs, conduct norms and behavior patterns that
      are HIV/AIDS risk factors for disaster survivors. This paper examines patterns of
      behavior and common practices related to HIV among disaster survivors. STUDY
      BACKGROUND: Data for this paper come from a three year renewal project which
      focused upon the processes by which illicit drug markets were reformulated after
      disasters and practices of risk behaviors for HIV/AIDS. Hurricanes Katrina,
      Gustav and Ike presented the opportunity to examine the impact of disasters upon
      risky behavior among illicit drug users and sellers. METHODS: From 2010-2013
      ethnographic study was conducted in New Orleans, Louisiana, Houston and
      Galveston, Texas. Staff completed in-depth interviews with 132 focal respondents
      of drug users and sellers. There were 57 focus groups with 243 focus group
      participants; 350 drug using/selling respondents completed a survey protocol
      (CAPI), organized around their experiences during the hurricanes. RESULTS: In
      both cities respondents displayed knowledge about HIV, modes of transmission and
      knew that HIV infection can lead to AIDS. Knowledge about time between exposure
      and infection was mostly imprecise. Most respondents reported they had been
      tested for HIV multiple times. A large number of participants reported learning
      about HIV in school, older respondents (mid-40s to 60) reported their knowledge
      came from television or the streets. Participants expressed fatalistic attitudes
      toward HIV, believing the virus was fatal even with medication. CONCLUSION: With
      the increase of disasters, more attention needs to be placed upon programs
      focused on drug consumers. Schools, clinics, public information sources, i.e., TV
      and radio can make understanding HIV/AIDS a priority through taking into
      consideration specific populations and making sure literature and other forms of
      information is adjusted to their understanding.

PMID- 27034965
TI  - Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells.
AB  - Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus
      erythematosus (SLE), an autoimmune disease with multiple tissue manifestations.
      In this review, we summarize recent studies on the roles of conventional DC and
      plasmacytoid DC in the development of both murine lupus and human SLE. In the
      past decade, studies using selective DC depletions have demonstrated critical
      roles of DC in lupus progression. Comprehensive in vitro and in vivo studies
      suggest activation of DC by self-antigens in lupus pathogenesis, followed by
      breakdown of immune tolerance to self. Potential treatment strategies targeting
      DC have been developed. However, many questions remain regarding the mechanisms
      by which DC modulate lupus pathogenesis that require further investigations. 

PMID- 27034968
TI  - 3' Rapid Amplification of cDNA Ends (3' RACE) Using Arabidopsis Samples.
AB  - Production of functional eukaryotic RNA is a very elaborate process that involves
      a complex interplay between transcription and various RNA processing activities,
      including splicing, 5' capping, and 3' cleavage and polyadenylation (Bentley,
      2014). Accurate mapping of RNA ends provides a valuable tool to assess
      transcriptional and post-transcriptional events giving rise to different gene
      transcripts. The abundance of such transcripts most likely depends on exogenous
      and developmental cues, or mutations. In the reference plant Arabidopsis,
      perturbation of the HUA-PEP post-transcriptional regulatory factors (Rodriguez
      Cazorla et al., 2015) leads to the accumulation of aberrant transcripts of the
      key floral homeotic gene AGAMOUS (AG) (Yanofsky et al., 1990) that retain
      intronic sequence. It was determined by 3' RACE reactions that such erroneous
      transcripts correspond to premature processing and polyadenylation events taking
      place at the AG intron region. Here we describe a protocol that is suitable for
      analysis of relatively abundant transcripts and also for detecting aberrant RNA
      species that are likely prone to rapid turnover. Likewise, the method, here
      adapted to Arabidopsis reproductive tissues, can be applied to characterize RNA
      species from other organs (leaf, root) and/or other plant species. We provide a
      detailed protocol of our 3' RACE procedure comprising four major parts: Total RNA
      extraction, RNA amount determination and quality control, the RACE procedure
      itself, and isolation of the resulting RACE products for cloning and sequencing.

PMID- 27034969
TI  - Differentiation of THP1 Cells into Macrophages for Transwell Co-culture Assay
      with Melanoma Cells.
AB  - Understanding how immune cells such as macrophages interact with cancer cells is
      of increasing interest, as cancer treatments move towards combining both targeted
      and immuno- therapies in new treatment regimes. This protocol is using THP-1
      cells, a human leukemia monocytic cell line that can be differentiated into
      macrophages. This allows studying the effects of the macrophage secretome on
      cancer cells (on e.g. growth, drug response or gene expression) in co-cultures
      without direct cell contact interactions. This is an important aspect as it
      removes the presence of any phagocytic aspect to changes in the cancer cell
      number and behaviour. The in vitro THP-1 monocyte differentiation into polarized
      macrophages was used to study the effects of both M1 and M2 type populations of
      macrophages on melanoma cells (Smith et al., 2014; Tsuchiya et al., 1980). M1
      type macrophages are classically thought to be tumour suppressing as opposed to
      M2 type macrophages, which are thought to possess tissue repairing and tumour
      growth promoting activities.

PMID- 27034970
TI  - Mouth Level Exposure and Similarity to Machine-smoked Constituent Yields.
AB  - OBJECTIVES: The goal of this review was to evaluate which standard machine
      smoking regimen may be most appropriate to inform tobacco product regulation
      based on the fraction of cigarette smoke yields that best represents the range of
      human smoke exposures. METHODS: We searched PubMed and Web of Science to identify
      peer-reviewed studies that reported percentages of smokers who smoked more or
      less like a particular machine-smoking regimen based on human mouth level
      exposure (MLE) tobacco constituent yields. RESULTS: Three studies met our
      inclusion criteria and were reviewed. Studies found that Canadian Intense (CI)
      yields were equal to or greater than 86% to 97% of smokers' nicotine and tar MLE
      yields. CONCLUSIONS: MLE yields indicate that a small percentage of individuals
      (less than 14%) are exposed to nicotine and tar yields equal to or greater than
      those measured by the CI regimen. Whereas no machine-smoking regimen reflects
      human puffing behavior with complete accuracy, based on MLE data, CI constituent
      yields constitute the best representation of exposure that encompasses the
      majority of smokers, and may be the most informative for regulatory purposes.

PMID- 27034971
TI  - An Automatic Multidocument Text Summarization Approach Based on Naive Bayesian
      Classifier Using Timestamp Strategy.
AB  - Nowadays, automatic multidocument text summarization systems can successfully
      retrieve the summary sentences from the input documents. But, it has many
      limitations such as inaccurate extraction to essential sentences, low coverage,
      poor coherence among the sentences, and redundancy. This paper introduces a new
      concept of timestamp approach with Naive Bayesian Classification approach for
      multidocument text summarization. The timestamp provides the summary an ordered
      look, which achieves the coherent looking summary. It extracts the more relevant
      information from the multiple documents. Here, scoring strategy is also used to
      calculate the score for the words to obtain the word frequency. The higher
      linguistic quality is estimated in terms of readability and comprehensibility. In
      order to show the efficiency of the proposed method, this paper presents the
      comparison between the proposed methods with the existing MEAD algorithm. The
      timestamp procedure is also applied on the MEAD algorithm and the results are
      examined with the proposed method. The results show that the proposed method
      results in lesser time than the existing MEAD algorithm to execute the
      summarization process. Moreover, the proposed method results in better precision,
      recall, and F-score than the existing clustering with lexical chaining approach. 

PMID- 27034972
TI  - Influence of Maternal and Postweaning Linseed Dietary Supplementation on Growth
      Rate, Lipid Profile, and Meat Quality Traits of Light Sarda Lambs.
AB  - The effects of dietary extruded linseed (EL) on growth performance, meat quality,
      and lipid profile of Semimembranosus and Longissimus lumborum muscles of 81 Sarda
      lambs were studied in a 3 * 3 design: EL content (0%, 10%, and 20%) of maternal
      dietary concentrate fed from 20 d to parturition to 60 d of lactation and EL
      content (0%, 10%, 20%) of lamb concentrate fed after weaning for 30 d. The basal
      diet was composed of alfalfa and meadow hay during pregnancy and alfalfa hay
      during lactation. At slaughter, carcass and meat quality were evaluated. Sensory
      quality of Semimembranosus from 0% and 20% EL lambs was assessed. Both maternal
      and postweaning diets affected growth performance, with higher body weights
      recorded with the 10% EL concentrate. Carcass and meat quality were not affected
      by diet. Saturated and monounsaturated FA decreased and n-3 polyunsaturated FA
      increased with increasing EL content in lamb diet. An increase in vaccenic and
      rumenic acid was associated with the EL content of the maternal diet. Both diets
      increased the n-6/n-3 FA ratio. No differences in acceptability were detected by
      consumers among groups. It is concluded that EL supplementation and early life
      nutrition can influence performance and FA metabolism in growing lambs.

PMID- 27034973
TI  - An Intelligent Ensemble Neural Network Model for Wind Speed Prediction in
      Renewable Energy Systems.
AB  - Various criteria are proposed to select the number of hidden neurons in
      artificial neural network (ANN) models and based on the criterion evolved an
      intelligent ensemble neural network model is proposed to predict wind speed in
      renewable energy applications. The intelligent ensemble neural model based wind
      speed forecasting is designed by averaging the forecasted values from multiple
      neural network models which includes multilayer perceptron (MLP), multilayer
      adaptive linear neuron (Madaline), back propagation neural network (BPN), and
      probabilistic neural network (PNN) so as to obtain better accuracy in wind speed
      prediction with minimum error. The random selection of hidden neurons numbers in
      artificial neural network results in overfitting or underfitting problem. This
      paper aims to avoid the occurrence of overfitting and underfitting problems. The
      selection of number of hidden neurons is done in this paper employing 102
      criteria; these evolved criteria are verified by the computed various error
      values. The proposed criteria for fixing hidden neurons are validated employing
      the convergence theorem. The proposed intelligent ensemble neural model is
      applied for wind speed prediction application considering the real time wind data
      collected from the nearby locations. The obtained simulation results substantiate
      that the proposed ensemble model reduces the error value to minimum and enhances
      the accuracy. The computed results prove the effectiveness of the proposed
      ensemble neural network (ENN) model with respect to the considered error factors
      in comparison with that of the earlier models available in the literature.

PMID- 27034974
TI  - Exact Inference for the Dispersion Matrix.
AB  - We develop a new and novel exact permutation test for prespecified correlation
      structures such as compound symmetry or spherical structures under standard
      assumptions. The key feature of the work contained in this note is the
      distribution free aspect of our procedures that frees us from the standard and
      sometimes unrealistic multivariate normality constraint commonly needed for other
      methods.

PMID- 27034975
TI  - An Innovative Approach to Evaluate the Morphological Patterns of Soft Palate in
      Oral Submucous Fibrosis Patients: A Digital Cephalometric Study.
AB  - Oral submucous fibrosis (OSMF) is a chronic insidious disease affecting mucosa
      and submucosa of oral cavity and soft palate. The present study aimed to evaluate
      the morphology of soft palate in normal individuals and OSMF patients using
      lateral cephalometry and to compare and correlate these variants of soft palate
      with different stages of OSMF. 100 subjects were included in the study, who were
      divided into two groups. Group I included 50 subjects with clinical diagnosis of
      OSMF and Group II included 50 normal subjects (control group). Using digital
      lateral cephalometry, velar length and width were measured and soft palatal
      patterns were categorized based on You et al.'s classification. Leaf and rat-tail
      patterns of soft palate were predominant in control group, whereas butt and crook
      shaped variants were more in study group. Anteroposterior (A-P) length of soft
      palate was significantly greater in stage I OSMF, while superoinferior (S-I)
      width was greater in stage III OSMF. Interestingly, a negative correlation was
      observed in staging of OSMF and A-P dimensions. As the staging of OSMF advances,
      the A-P length of soft palate decreases, but S-I width increases. 

PMID- 27034976
TI  - HOXs and lincRNAs: Two sides of the same coin.
AB  - The clustered Hox genes play fundamental roles in regulation of axial patterning
      and elaboration of the basic body plan in animal development. There are common
      features in the organization and regulatory landscape of Hox clusters associated
      with their highly conserved functional roles. The presence of transcribed
      noncoding sequences embedded within the vertebrate Hox clusters is providing
      insight into a new layer of regulatory information associated with Hox genes. 

PMID- 27034977
TI  - A case for historic joint rupture of the San Andreas and San Jacinto faults.
AB  - The San Andreas fault is considered to be the primary plate boundary fault in
      southern California and the most likely fault to produce a major earthquake. I
      use dynamic rupture modeling to show that the San Jacinto fault is capable of
      rupturing along with the San Andreas in a single earthquake, and interpret these
      results along with existing paleoseismic data and historic damage reports to
      suggest that this has likely occurred in the historic past. In particular, I find
      that paleoseismic data and historic observations for the ~M7.5 earthquake of 8
      December 1812 are best explained by a rupture that begins on the San Jacinto
      fault and propagates onto the San Andreas fault. This precedent carries the
      implications that similar joint ruptures are possible in the future and that the
      San Jacinto fault plays a more significant role in seismic hazard in southern
      California than previously considered. My work also shows how physics-based
      modeling can be used for interpreting paleoseismic data sets and understanding
      prehistoric fault behavior.

PMID- 27034978
TI  - Rapid assessment of disaster damage using social media activity.
AB  - Could social media data aid in disaster response and damage assessment? Countries
      face both an increasing frequency and an increasing intensity of natural
      disasters resulting from climate change. During such events, citizens turn to
      social media platforms for disaster-related communication and information. Social
      media improves situational awareness, facilitates dissemination of emergency
      information, enables early warning systems, and helps coordinate relief efforts.
      In addition, the spatiotemporal distribution of disaster-related messages helps
      with the real-time monitoring and assessment of the disaster itself. We present a
      multiscale analysis of Twitter activity before, during, and after Hurricane
      Sandy. We examine the online response of 50 metropolitan areas of the United
      States and find a strong relationship between proximity to Sandy's path and
      hurricane-related social media activity. We show that real and perceived threats,
      together with physical disaster effects, are directly observable through the
      intensity and composition of Twitter's message stream. We demonstrate that per
      capita Twitter activity strongly correlates with the per-capita economic damage
      inflicted by the hurricane. We verify our findings for a wide range of disasters
      and suggest that massive online social networks can be used for rapid assessment
      of damage caused by a large-scale disaster.

PMID- 27034979
TI  - Universal diffraction of atoms and molecules from a quantum reflection grating.
AB  - Since de Broglie's work on the wave nature of particles, various optical
      phenomena have been observed with matter waves of atoms and molecules. However,
      the analogy between classical and atom/molecule optics is not exact because of
      different dispersion relations. In addition, according to de Broglie's formula,
      different combinations of particle mass and velocity can give the same de Broglie
      wavelength. As a result, even for identical wavelengths, different molecular
      properties such as electric polarizabilities, Casimir-Polder forces, and
      dissociation energies modify (and potentially suppress) the resulting matter-wave
      optical phenomena such as diffraction intensities or interference effects. We
      report on the universal behavior observed in matter-wave diffraction of He atoms
      and He2 and D2 molecules from a ruled grating. Clear evidence for emerging beam
      resonances is observed in the diffraction patterns, which are quantitatively the
      same for all three particles and only depend on the de Broglie wavelength. A
      model, combining secondary scattering and quantum reflection, permits us to trace
      the observed universal behavior back to the peculiar principles of quantum
      reflection.

PMID- 27034980
TI  - Effects of conservation policy on China's forest recovery.
AB  - Forest loss is one of the most pervasive land surface transformations on Earth,
      with drastic effects on global climate, ecosystems, and human well-being. As part
      of biodiversity conservation and climate change mitigation efforts, many
      countries, including China, have been implementing large-scale policies to
      conserve and restore forests. However, little is known about the effectiveness of
      these policies, and information on China's forest dynamics at the national level
      has mainly relied on official statistics. In response to international calls for
      improved reliability and transparency of information on biodiversity conservation
      and climate change mitigation efforts, it is crucial to independently verify
      government statistics. Furthermore, if forest recovery is verified, it is
      essential to assess the degree to which this recovery is attributable to policy,
      within the context of other relevant factors. We assess the dynamics of forest
      cover in China between 2000 and 2010 and evaluate the effectiveness of one of the
      largest forest conservation programs in the world-the Natural Forest Conservation
      Program (NFCP). Results indicate that forest cover has significantly increased in
      around 1.6% of China's territory and that the areas exhibiting forest gain
      experienced a combined increase in net primary productivity (ca. 0.9 Tg of
      carbon). Among the variables evaluated at county level, the NFCP exhibited a
      significantly positive relation with forest gain, whereas reduction in rural
      labor showed a negative relationship with both forest loss and gain. Findings
      such as these have global implications for forest conservation and climate change
      mitigation efforts.

PMID- 27034981
TI  - Critical role of intercalated water for electrocatalytically active nitrogen
      doped graphitic systems.
AB  - Graphitic materials are essential in energy conversion and storage because of
      their excellent chemical and electrical properties. The strategy for obtaining
      functional graphitic materials involves graphite oxidation and subsequent
      dissolution in aqueous media, forming graphene-oxide nanosheets (GNs). Restacked
      GNs contain substantial intercalated water that can react with heteroatom dopants
      or the graphene lattice during reduction. We demonstrate that removal of
      intercalated water using simple solvent treatments causes significant structural
      reorganization, substantially affecting the oxygen reduction reaction (ORR)
      activity and stability of nitrogen-doped graphitic systems. Amid contrasting
      reports describing the ORR activity of GN-based catalysts in alkaline
      electrolytes, we demonstrate superior activity in an acidic electrolyte with an
      onset potential of ~0.9 V, a half-wave potential (E 1/2) of 0.71 V, and a
      selectivity for four-electron reduction of >95%. Further, durability testing
      showed E 1/2 retention >95% in N2- and O2-saturated solutions after 2000 cycles,
      demonstrating the highest ORR activity and stability reported to date for GN
      based electrocatalysts in acidic media.

PMID- 27034982
TI  - Why do some males choose to breed at home when most other males disperse?
AB  - Dispersal is a key driver of ecological and evolutionary processes. Despite
      substantial efforts to explain the evolution of dispersal, we still do not fully
      understand why individuals of the same sex of a species vary in their propensity
      to disperse. The dominant hypothesis emphasizes movements and assumes that
      leaving home (dispersal) and staying at home (philopatry) are two alternative
      strategies providing different fitness. It suggests that only individuals of high
      phenotypic quality can pursue the most beneficial strategy; the others are left
      to do a "best-of-a-bad" job. An alternative hypothesis emphasizes settlement
      decisions and suggests that all individuals pursue a single strategy of choosing
      the breeding habitat or group with the highest fitness prospects; choosing the
      natal group (philopatry) and choosing a nonnatal group (dispersal) are then
      outcomes of these decisions. We tested both hypotheses using a long-term study of
      a free-ranging population of a group-living carnivore, the spotted hyena. We
      combined demographic data with data on dispersal-relevant phenotypic traits,
      breeding-group choice, survival, and reproductive success of 254 males. Our
      results contradict the best-of-a-bad-job hypothesis: philopatric males and
      dispersers were of similar phenotypic quality, had similar fitness, and applied
      similar settlement rules based on the fitness prospects in groups. Our findings
      demonstrate that the distribution of breeding partners can be more important in
      shaping dispersal patterns than the costs associated with the dispersal movement.
      The study provides novel insights into the processes leading to the coexistence
      of philopatry and dispersal within the same sex of a species.

PMID- 27034983
TI  - Cavity magnomechanics.
AB  - A dielectric body couples with electromagnetic fields through radiation pressure
      and electrostrictive forces, which mediate phonon-photon coupling in cavity
      optomechanics. In a magnetic medium, according to the Korteweg-Helmholtz formula,
      which describes the electromagnetic force density acting on a medium,
      magneostrictive forces should arise and lead to phonon-magnon interaction. We
      report such a coupled phonon-magnon system based on ferrimagnetic spheres, which
      we term as cavity magnomechanics, by analogy to cavity optomechanics. Coherent
      phonon-magnon interactions, including electromagnetically induced transparency
      and absorption, are demonstrated. Because of the strong hybridization of magnon
      and microwave photon modes and their high tunability, our platform exhibits new
      features including parametric amplification of magnons and phonons, triple
      resonant photon-magnon-phonon coupling, and phonon lasing. Our work demonstrates
      the fundamental principle of cavity magnomechanics and its application as a new
      information transduction platform based on coherent coupling between photons,
      phonons, and magnons.

PMID- 27034984
TI  - Mutations in chromatin machinery and pediatric high-grade glioma.
AB  - Pediatric central nervous system tumors are the most common solid tumor of
      childhood. Of these, approximately one-third are gliomas that exhibit diverse
      biological behaviors in the unique context of the developing nervous system.
      Although low-grade gliomas predominate and have favorable outcomes, up to 20% of
      pediatric gliomas are high-grade. These tumors are a major contributor to cancer
      related morbidity and mortality in infants, children, and adolescents, with long
      term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic
      mutations affecting chromatin regulation in pediatric high-grade glioma has
      markedly improved our understanding of disease pathogenesis, and these findings
      have stimulated the development of novel therapeutic approaches targeting
      epigenetic regulators for disease treatment. We review the current perspective on
      pediatric high-grade glioma genetics and epigenetics, and discuss the emerging
      and experimental therapeutics targeting the unique molecular abnormalities
      present in these deadly childhood brain tumors.

PMID- 27034985
TI  - Assessing faculty professional development in STEM higher education:
      Sustainability of outcomes.
AB  - We tested the effectiveness of Faculty Institutes for Reforming Science Teaching
      IV (FIRST), a professional development program for postdoctoral scholars, by
      conducting a study of program alumni. Faculty professional development programs
      are critical components of efforts to improve teaching and learning in the STEM
      (Science, Technology, Engineering, and Mathematics) disciplines, but reliable
      evidence of the sustained impacts of these programs is lacking. We used a paired
      design in which we matched a FIRST alumnus employed in a tenure-track position
      with a non-FIRST faculty member at the same institution. The members of a pair
      taught courses that were of similar size and level. To determine whether teaching
      practices of FIRST participants were more learner-centered than those of non
      FIRST faculty, we compared faculty perceptions of their teaching strategies,
      perceptions of environmental factors that influence teaching, and actual teaching
      practice. Non-FIRST and FIRST faculty reported similar perceptions of their
      teaching strategies and teaching environment. FIRST faculty reported using active
      learning and interactive engagement in lecture sessions more frequently compared
      with non-FIRST faculty. Ratings from external reviewers also documented that
      FIRST faculty taught class sessions that were learner-centered, contrasting with
      the teacher-centered class sessions of most non-FIRST faculty. Despite marked
      differences in teaching practice, FIRST and non-FIRST participants used
      assessments that targeted lower-level cognitive skills. Our study demonstrated
      the effectiveness of the FIRST program and the empirical utility of comparison
      groups, where groups are well matched and controlled for contextual variables
      (for example, departments), for evaluating the effectiveness of professional
      development for subsequent teaching practices.

PMID- 27034986
TI  - FOXA1 defines cancer cell specificity.
AB  - A transcription factor functions differentially and/or identically in multiple
      cell types. However, the mechanism for cell-specific regulation of a
      transcription factor remains to be elucidated. We address how a single
      transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific
      genomic signatures and differentially regulates gene expression in four human
      cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer
      transcription factor in organogenesis and cancer progression. Genomewide mapping
      of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes
      associated with FOXA1 binding are mostly common to these cancer cells. However,
      most of the functional FOXA1 target genes are specific to each cancer cell type.
      Further investigations using CRISPR-Cas9 genome editing technology indicate that
      cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic
      variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the
      specificity of cancer cell types. We raise a "flower-blooming" hypothesis for
      cell-specific transcriptional regulation based on these observations.

PMID- 27034987
TI  - Electromagnetic stress at the boundary: Photon pressure or tension?
AB  - It is well known that incident photons carrying momentum hk exert a positive
      photon pressure. But if light is impinging from a negative refractive medium in
      which hk is directed toward the source of radiation, should light exert a photon
      "tension" instead of a photon pressure? Using an ab initio method that takes the
      underlying microstructure of a material into account, we find that when an
      electromagnetic wave propagates from one material into another, the
      electromagnetic stress at the boundary is, in fact, indeterminate if only the
      macroscopic parameters are specified. Light can either pull or push the boundary,
      depending not only on the macroscopic parameters but also on the microscopic
      lattice structure of the polarizable units that constitute the medium. Within the
      context of an effective-medium approach, the lattice effect is attributed to
      electrostriction and magnetostriction, which can be accounted for by the
      Helmholtz stress tensor if we use the macroscopic fields to calculate the
      boundary optical stress.

PMID- 27034988
TI  - Universal dependence of hydrogen oxidation and evolution reaction activity of
      platinum-group metals on pH and hydrogen binding energy.
AB  - Understanding how pH affects the activity of hydrogen oxidation reaction (HOR)
      and hydrogen evolution reaction (HER) is key to developing active, stable, and
      affordable HOR/HER catalysts for hydroxide exchange membrane fuel cells and
      electrolyzers. A common linear correlation between hydrogen binding energy (HBE)
      and pH is observed for four supported platinum-group metal catalysts (Pt/C, Ir/C,
      Pd/C, and Rh/C) over a broad pH range (0 to 13), suggesting that the pH
      dependence of HBE is metal-independent. A universal correlation between exchange
      current density and HBE is also observed on the four metals, indicating that they
      may share the same elementary steps and rate-determining steps and that the HBE
      is the dominant descriptor for HOR/HER activities. The onset potential of CO
      stripping on the four metals decreases with pH, indicating a stronger OH
      adsorption, which provides evidence against the promoting effect of adsorbed OH
      on HOR/HER.

PMID- 27034989
TI  - Inverse correlation between quasiparticle mass and T c in a cuprate high-T c
      superconductor.
AB  - Close to a zero-temperature transition between ordered and disordered electronic
      phases, quantum fluctuations can lead to a strong enhancement of electron mass
      and to the emergence of competing phases such as superconductivity. A correlation
      between the existence of such a quantum phase transition and superconductivity is
      quite well established in some heavy fermion and iron-based superconductors, and
      there have been suggestions that high-temperature superconductivity in copper
      oxide materials (cuprates) may also be driven by the same mechanism. Close to
      optimal doping, where the superconducting transition temperature T c is maximal
      in cuprates, two different phases are known to compete with superconductivity: a
      poorly understood pseudogap phase and a charge-ordered phase. Recent experiments
      have shown a strong increase in quasiparticle mass m* in the cuprate YBa2Cu3O7
      delta as optimal doping is approached, suggesting that quantum fluctuations of
      the charge-ordered phase may be responsible for the high-T c superconductivity.
      We have tested the robustness of this correlation between m* and T c by
      performing quantum oscillation studies on the stoichiometric compound YBa2Cu4O8
      under hydrostatic pressure. In contrast to the results for YBa2Cu3O7-delta, we
      find that in YBa2Cu4O8, the mass decreases as T c increases under pressure. This
      inverse correlation between m* and T c suggests that quantum fluctuations of the
      charge order enhance m* but do not enhance T c.

PMID- 27034990
TI  - Harnessing surface-bound enzymatic reactions to organize microcapsules in
      solution.
AB  - By developing new computational models, we examine how enzymatic reactions on an
      underlying surface can be harnessed to direct the motion and organization of
      reagent-laden microcapsules in a fluid-filled microchannel. In the presence of
      appropriate reagents, surface-bound enzymes can act as pumps, which drive large
      scale fluid flows. When the reagents diffuse through the capsules' porous shells,
      they can react with enzymatic sites on the bottom surface. The ensuing reaction
      generates fluid density variations, which result in fluid flows. These flows
      carry the suspended microcapsules and drive them to aggregate into "colonies" on
      and near the enzyme-covered sites. This aggregation continues until the reagent
      has been depleted and the convection stops. We show that the shape of the
      assembled colonies can be tailored by patterning the distribution of enzymes on
      the surface. This fundamental physicochemical mechanism could have played a role
      in the self-organization of early biological cells (protocells) and can be used
      to regulate the autonomous motion and targeted delivery of microcarriers in
      microfluidic devices.

PMID- 27034991
TI  - Survey for human polyomaviruses in cancer.
AB  - Over the past 8 years, the discovery of 11 new human polyomaviruses (HPyVs) has
      revived interest in this DNA tumor virus family. Although HPyV infection is
      widespread and largely asymptomatic, one of these HPyVs, Merkel cell polyomavirus
      (MCV), is a bona fide human tumor virus. JC virus (JCV), BK virus, HPyV7, and
      trichodysplasia-spinulosa virus (TSV) can cause nonneoplastic diseases in the
      setting of immunosuppression. Few specific reagents are available to study the
      biology of the newly discovered HPyVs. We developed a pan-HPyV-screening method
      using a cocktail of 3 antibodies that, when combined, recognize T antigen
      proteins of all HPyVs. We validated detection characteristics of the antibody
      cocktail by immunoblotting and immunohistochemistry and screened 1,184 cases,
      including well-defined diseases and tumor tissue microarrays. This assay robustly
      detected MCV, TSV, JCV, and HPyV7 in etiologically related diseases. We further
      identified WU polyomavirus in a case of chronic lymphocytic lymphoma-associated
      bronchitis. Except for scattered, incidentally infected cells in 5% of lung
      squamous cell carcinomas and colon adenocarcinomas, a broad panel of tumor
      tissues was largely negative for infection by any HPyV. This method eliminates
      known HPyVs as suspected causes of cancers investigated in this study. Pan-HPyV
      survey can be applied to identify diseases associated with recently discovered
      polyomaviruses.

PMID- 27034992
TI  - A Review of Smartphone Applications for Promoting Physical Activity.
AB  - INTRODUCTION: Rapid developments in technology have encouraged the use of
      smartphones in health promotion research and practice. Although many applications
      (apps) relating to physical activity are available from major smartphone
      platforms, relatively few have been tested in research studies to determine their
      effectiveness in promoting health. METHODS: In this article, we summarize data on
      use of smartphone apps for promoting physical activity based upon bibliographic
      searches with relevant search terms in PubMed and CINAHL. RESULTS: After
      screening the abstracts or full texts of articles, 15 eligible studies of the
      acceptability or efficacy of smartphone apps for increasing physical activity
      were identified. Of the 15 included studies, 6 were qualitative research studies,
      8 were randomized control trials, and one was a nonrandomized study with a pre
      post design. The results indicate that smartphone apps can be efficacious in
      promoting physical activity although the magnitude of the intervention effect is
      modest. Participants of various ages and genders respond favorably to apps that
      automatically track physical activity (e.g., steps taken), track progress toward
      physical activity goals, and are user-friendly and flexible enough for use with
      several types of physical activity. DISCUSSION: Future studies should utilize
      randomized controlled trial research designs, larger sample sizes, and longer
      study periods to establish the physical activity measurement and intervention
      capabilities of smartphones. There is a need for culturally appropriate, tailored
      health messages to increase knowledge and awareness of health behaviors such as
      physical activity.

PMID- 27034993
TI  - A review of community-based participatory research studies to promote physical
      activity among African Americans.
AB  - BACKGROUND: As part of the planning process for new research, the literature on
      community-based participatory research (CBPR) approaches for promoting physical
      activity in African American communities was systematically reviewed. METHODS:
      Studies published through October 31, 2015 that employed CBPR methods were
      identified using PubMed and CINAHL databases and MeSH terms and keyword searches.
      RESULTS: A total of 15 studies met the search criteria. One focused on CBPR and
      physical activity among African American school children and adolescents, 13 on
      adults, and one on both children and adults. Seven studies employed CBPR methods
      to promote physical activity in church settings. Eight of the studies had a pre
      /post-test design, three had a quasi-experimental design, three had a randomized
      controlled design, and one was a case study. CONCLUSIONS: Additional CBPR studies
      and faith-based interventions are needed to identify effective ways to promote
      physical activity in African American communities to address health disparities.
      Of particular interest are those that have an adequate sample size and a rigorous
      design, to overcome limitations of previous studies.

PMID- 27034994
TI  - The need for culturally-tailored smartphone applications for weight control.
AB  - BACKGROUND: Approximately 35% of U.S. adults are obese, and this rate is expected
      to increase by almost 50% by 2030. New media such as smartphone applications
      (apps) provide a useful and low-cost way to disseminate weight control
      information. For many culturally distinctive population subgroups, however, there
      is currently an absence of research-tested smartphone apps for weight control.
      METHODS: In this commentary, we highlight the need for culturally tailored
      smartphone apps for weight control and offer recommendations for further research
      by providing two specific examples: 1) the characteristic dietary patterns and
      absence of smartphone apps for weight loss for Hispanic Americans, in English and
      Spanish, and 2) and need for smartphone apps for weight loss for Brazilian
      Americans, including those who speak Portuguese. RESULTS: Smartphone apps can be
      an effective intervention for improving diet and nutrition, encouraging physical
      activity, and reducing obesity, but few randomized controlled trials have been
      conducted of stand-alone smartphone apps for weight loss that focus primarily on
      self-monitoring of diet and physical activity. Further, there have been no
      published studies of apps for promoting healthy diet, better nutrition,
      increasing levels of physical activity, and weight loss among Hispanic Americans
      or Brazilian Americans. CONCLUSIONS: Low-cost, effective e-Health interventions
      (healthcare practices supported by electronic processes) are needed to promote
      physical activity, healthy eating, and weight control in culturally distinctive
      subgroups of the population. For weight loss, apps should be developed by use of
      evidence-based approaches that relate to behavioral theories. Additional public
      health research is needed to identify low-cost, effective strategies for weight
      loss for people who have varying levels of health literacy, and for non-English
      speakers. Culturally tailored e-Health interventions for weight control are more
      likely to address the needs of individuals and increase their motivation to
      engage in health promoting behaviors.

PMID- 27034995
TI  - Simulation of lipid bilayer self-assembly using all-atom lipid force fields.
AB  - In this manuscript we expand significantly on our earlier communication by
      investigating the bilayer self-assembly of eight different types of phospholipids
      in unbiased molecular dynamics (MD) simulations using three widely used all-atom
      lipid force fields. Irrespective of the underlying force field, the lipids are
      shown to spontaneously form stable lamellar bilayer structures within 1
      microsecond, the majority of which display properties in satisfactory agreement
      with the experimental data. The lipids self-assemble via the same general
      mechanism, though at formation rates that differ both between lipid types, force
      fields and even repeats on the same lipid/force field combination. In addition to
      zwitterionic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids,
      anionic phosphatidylserine (PS) and phosphatidylglycerol (PG) lipids are
      represented. To our knowledge this is the first time bilayer self-assembly of
      phospholipids with negatively charged head groups is demonstrated in all-atom MD
      simulations. 

PMID- 27034996
TI  - Sheath flow SERS for chemical profiling in urine.
AB  - The molecular specificity and sensitivity of surface enhanced Raman scattering
      (SERS) makes it an attractive method for biomedical diagnostics. Here we present
      results demonstrating the utility and complications for SERS characterization in
      urine. The chemical fingerprint characteristics of Raman spectra suggest its use
      as a label free diagnostic; however, the complex composition of biological fluids
      presents a tremendous challenge. In particular, the limited number of surface
      sites and competing absorption tend to mask the presence of analytes in solution,
      particularly when the solution contains multiple analytes. To address these
      problems and characterize biological fluids we have demonstrated a sheath-flow
      interface for SERS detection. This sheath-flow SERS interface uses hydrodynamic
      focusing to confine analyte molecules eluting out of a column onto a planar SERS
      substrate where the molecules are detected by their intrinsic SERS signal. In
      this report we compare the direct detection of benzoylecgonine in urine using
      DSERS with chemical profiling by capillary zone electrophoresis and sheath-flow
      SERS detection. The SERS spectrum from the observed migration peaks can identify
      benzoylecgonine and other distinct spectra are also observed, suggesting improved
      chemical diagnostics in urine. With over 2000 reported compounds in urine,
      identification of each of the detected species is an enormous task. Nonetheless,
      these samples provide a benchmark to establish the potential clinical utility of
      sheath-flow SERS detection.

PMID- 27034997
TI  - From synthetic DNA to PCR product: detection of fungal infections using SERS.
AB  - We report the use of silver hydroxylamine nanoparticles functionalised with
      single stranded monothiolated DNA for the detection of fungal infections. The
      four different species of fungi that were targeted were Candida albicans, Candida
      glabrata, Candida krusei and Aspergillus fumigatus. Rational design of synthetic
      targets and probes was carried out by carefully analysing the 2-D folding of the
      DNA and then by global alignment of the sequences to ensure specificity. The
      effects of varying the concentrations of the DNA and dye surrounding the
      nanoparticles on the resultant surface enhanced Raman scattering (SERS) signal
      were also investigated to ensure compatibility of the probes in a multiplexed
      environment. Using principal components analysis (PCA) it was possible to detect
      the individual presence of each target and group them accordingly. The move to
      detect the C. krusei single stranded PCR product (ssPCR) was significant to
      demonstrate that the methodology could be employed for the detection and
      diagnosis of invasive fungal infections (IFDs) within a clinical setting.
      Initially the PCR product was subjected to an alkali shock method in order to
      separate the strands ready for detection using the nanoparticle probes system.
      This time 18 base probes were employed to enhance hybridisation efficiency and
      dextran sulfate was found to have a vital role in ensuring that detection of the
      C. krusei target was achieved. This demonstrated the use of DNA functionalised
      silver nanoparticle for the detection of clinically relevant DNA relating to a
      specific fungal infection and offers significant promise for future diagnostic
      applications.

PMID- 27034998
TI  - Mie scatter corrections in single cell infrared microspectroscopy.
AB  - Strong Mie scattering signatures hamper the chemical interpretation and
      multivariate analysis of the infrared microscopy spectra of single cells and
      tissues. During recent years, several numerical Mie scatter correction algorithms
      for the infrared spectroscopy of single cells have been published. In the paper
      at hand, we critically reviewed existing algorithms for the correction of Mie
      scattering and suggest improvements. We developed an iterative algorithm based on
      Extended Multiplicative Scatter Correction (EMSC), for the retrieval of pure
      absorbance spectra from highly distorted infrared spectra of single cells. The
      new algorithm uses the van de Hulst approximation formula for the extinction
      efficiency employing a complex refractive index. The iterative algorithm involves
      the establishment of an EMSC meta-model. While existing iterative algorithms for
      the correction of resonant Mie scattering employ three independent parameters for
      establishing a meta-model, we could decrease the number of parameters from three
      to two independent parameters, which reduced the calculation time for the Mie
      scattering curves for the iterative EMSC meta-model by a factor of 10. Moreover,
      by employing the Hilbert transform for evaluating the Kramers-Kronig relations
      based on a FFT algorithm in Matlab, we further improved the speed of the
      algorithm by a factor of 100. For testing the algorithm we simulate distorted
      apparent absorbance spectra by utilizing the exact theory for the scattering of
      infrared light at absorbing spheres, taking into account the high numerical
      aperture of infrared microscopes employed for the analysis of single cells and
      tissues. In addition, the algorithm was applied to measured absorbance spectra of
      single lung cancer cells.

PMID- 27034999
TI  - Meeting Report: Fungal Genomics Meets Social  Media: Highlights of the 28th
      Fungal Genetics  Conference at Asilomar.

PMID- 27035000
TI  - [Neurological complications due to vitamin deficiencies after bariatric surgery].
AB  - The most effective treatment for pathological obesity is bariatric surgery;
      however, a patient may postoperatively develop vitamin deficiencies. In
      inadequate intake of food and its malabsorption after surgery, there are chiefly
      deficiencies of vitamins B1, B6, B12, and vitamin E, leading to complications as
      central and peripheral nervous system dysfunctions. The most marked nervous
      system changes are observed as polyneuropathy and severe Wernicke's
      encephalopathy in vitamin B, deficiency. Vitamin B12 deficiency clinically
      manifests as funicular myelosis and polyneuropathy. Polyneuropathy results from
      the inadequate intake of Vitamin B6 and vitamin E. The larger number of bariatric
      surgical patients generates a need for alertness to the development of
      neurological complications in this cohort of patients as only early treatment
      initiation guarantees a favorable outcome of neurologic deficit.

PMID- 27035001
TI  - [Multiple endocrine neoplasia type 1 syndrome with three classical components and
      chiasm glioma: specific features of target organ lesions and a clinical
      observation].
AB  - The article briefly reviews the specific features of target-organ lesions in
      multiple endocrine neoplasia type 1 (MEN1) syndrome and a clinical case of
      genetically confirmed MEN1 syndrome in a young female patient. Despite the
      relative rarity of this disease, timely diagnosis, treatment and screening for
      its main components are very important for the overall prognosis of patients with
      MEN1 and their first-degree relatives who are MEN1 gene mutation carriers. The
      described case is noteworthy for a number of specific features. The authors could
      find no account of optic chiasm glioma within the framework of MEN1 in the
      literature. Moreover, therapy-resistant somatoprolactinoma engages attention,
      which points to its aggressive nature with pituitary adenoma that is not been
      clearly visualized on magnetic resonance imaging. Of interest is the order of
      detection of neoplasms, in particular the manifestation of hypoglycemic episodes
      as a sign of organic hyperinsulinism. which have been initially regarded as
      epileptic seizures, after the use of sustained-release somatostatin analogues for
      the treatment of acromegaly.

PMID- 27035002
TI  - [Metabolic and hemodynamic effects of the growth hormone system - insulin-like
      growth factor].
AB  - Significant congenital deficiency of growth factor (GF) results in pituitary
      nanism (dwarfism) and its substantial excess is accompanied by the development of
      gigantism or acromegaly. Its impact on the growth of the whole body or its
      individual parts is impossible without affecting metabolic processes and
      hemodynamic parameters. A number of investigations have proven that GF has a
      direct lipolytic effect: adequate replacement therapy for pituitary nanism gives
      rise to a reduction in fat depots. Since the concentration of GF is lower in
      obesity, Whether it may be used to treat this abnormality is considered.

PMID- 27035003
TI  - [Rebamipide: New opportunities of gastroenteroprotection].
AB  - This review paper deals with the prevention and therapy of nonsteroidal anti
      inflammatory drug (NSAID)-induced gastrointestinal mucosal injuries in patients
      with disease of the cardiovascular and locomotor systems. Particular emphasis is
      laid on the new Russian drug rebamibide that is a stimulant of prostaglandin and
      glycoprotein synthesis and an inhibitor of the synthesis of oxidative stress
      products, inflammatory cytokines, and chemokines in the gastrointestinal mucosa.
      The advantage of rebamipide over classical gastroprotectors is its proven
      additional effect on the small and large intestinal mucosa. This drug has been
      registered and is actively used in a number of countries, including Japan, South
      Korea, and China.

PMID- 27035004
TI  - [Linex forte in the prevention and treatment of gastrointestinal diseases].
AB  - The paper discusses the properties of Lactobacillus acidophilus (LA-5) and
      Bifidobacterium animals subsp. lactis (BB-12) that are active ingredients of
      linex forte, as well as the results of their experimental and clinical studies in
      gastroenterology. It states dosing recommendations for the drug to treat
      gastrointestinal tract diseases in adults and children.

PMID- 27035005
TI  - Patients' awareness of the surgical risks of smoking: Implications for supporting
      smoking cessation.
AB  - OBJECTIVE: To describe the smoking patterns of patients receiving elective
      surgery and their knowledge about the benefits of smoking cessation to inform and
      strengthen support for patients to quit smoking in order to optimize surgical
      outcomes. DESIGN: Patients who had elective surgery were screened for smoking
      status, and eligible patients completed a telephone survey. SETTING: Two regional
      hospitals in northern British Columbia. PARTICIPANTS: Of 1722 patients screened,
      373 reported smoking before surgery. Of these, 161 (59.0% women) completed a
      telephone survey. MAIN OUTCOME MEASURES: Patient smoking cessation, knowledge of
      the perioperative risks of smoking, use of resources, and health care provider
      advice and assistance. RESULTS: Participants included 66 men and 95 women (mean
      [SD] age of 51.9 [14.0] years). In total, 7.5% of these patients quit smoking in
      the 8 weeks before their surgeries, although an additional 38.8% reduced their
      smoking. Only about half of the patients surveyed were aware that continuing to
      smoke increased their surgical risks. Further, only half of the patients surveyed
      reported being advised to quit before their surgeries by a health care
      professional. Few were using the provincial resources available to support
      smoking cessation (eg, QuitNow), and 39.6% were unaware of the provincial program
      to cover the cost of smoking cessation aids (eg, nicotine gum or patches), yet
      62.7% of respondents were thinking about quitting smoking. CONCLUSION: Many
      surgical patients in northern British Columbia who smoked were unaware of the
      perioperative risks of smoking and the cessation support available to them. An
      opportunity exists for all health care professionals to encourage more patients
      to quit in order to optimize their surgical outcomes.

PMID- 27035006
TI  - Rooming-in care for infants of opioid-dependent mothers: Implementation and
      evaluation at a tertiary care hospital.
AB  - PROBLEM ADDRESSED: Infants born to opioid-dependent women are admitted to
      intensive care units for management of neonatal abstinence syndrome (NAS),
      serious morbidity, and prevention of mortality; however, the disadvantages of
      this approach include infants experiencing more severe NAS and exhibiting a
      greater need for pharmacotherapy owing to the interference with mother-infant
      bonding. OBJECTIVE OF PROGRAM: To implement a rooming-in program to support close
      uninterrupted contact between opioid-dependent women and their infants in order
      to decrease the severity of NAS scores, lessen the need for pharmacotherapy, and
      shorten hospital stays. PROGRAM DESCRIPTION: Opioid-dependent pregnant women were
      assessed antenatally by a multidisciplinary team and provided with education and
      support. Psychosocial issues were addressed in collaboration with a community
      program developed to support addicted mothers. The mother-infant dyad was
      admitted postpartum to a private room and attended by nurses trained in Finnegan
      scoring. Infants remained with their mothers unless persistently elevated scores
      made transfer to neonatal intensive care units necessary for initiation of
      pharmacotherapy. CONCLUSION: With the rooming-in program, the proportion of
      infants requiring pharmacotherapy decreased from 83.3% to 14.3% (P < .001) and
      the average length of stay decreased from 25 days to 8 days (P < .001). The
      rooming-in experience was rated favourably by participating mothers.

PMID- 27035007
TI  - Data discipline in electronic medical records: Improving smoking status
      documentation with a standardized intake tool and process.
AB  - OBJECTIVE: To evaluate the transformation in smoking status documentation after
      implementing a standardized intake tool as part of a primary care smoking
      cessation program. DESIGN: A before-and-after evaluation of smoking status
      documentation was conducted following implementation of a smoking assessment
      tool. To evaluate the effect of the intervention, the Canadian Primary Care
      Sentinel Surveillance Network was used to extract aggregate smoking data on the
      study cohort. SETTING: Academic primary care clinic in Kingston, Ont.
      PARTICIPANTS: A total of 7312 primary care patients. INTERVENTIONS: As the first
      phase in a primary care smoking cessation program, a standardized intake tool was
      developed as part of a vital signs screening process. MAIN OUTCOME MEASURES:
      Documented smoking status of patients before implementation of the intake tool
      and documented smoking status of patients in the 6 months after its
      implementation. RESULTS: Following the implementation of the standardized intake
      tool, there was a 55% (P < .001; 95% CI 0.53 to 0.56) increase in the proportion
      of patients with a completed smoking status; more than 1100 former smokers were
      identified and the documented smoking rate in this cohort increased from 4.4% to
      16.2%. CONCLUSION: This study shows that the implementation of an intake tool,
      integrated into existing clinical operational structures, is an effective way to
      standardize clinical documentation and promotes the optimization of electronic
      medical records.

PMID- 27035008
TI  - Are family medicine residents adequately trained to deliver palliative care?
AB  - OBJECTIVE: To explore educational factors that influence family medicine
      residents' (FMRs') intentions to offer palliative care and palliative care home
      visits to patients. DESIGN: Qualitative descriptive study. SETTING: A Canadian,
      urban, specialized palliative care centre. PARTICIPANTS: First-year (n = 9) and
      second-year (n = 6) FMRs. METHODS: Semistructured interviews were conducted with
      FMRs following a 4-week palliative care rotation. Questions focused on
      participant experiences during the rotation and perceptions about their roles as
      family physicians in the delivery of palliative care and home visits. Participant
      responses were analyzed to summarize and interpret patterns related to their
      educational experience during their rotation. MAIN FINDINGS: Four interrelated
      themes were identified that described this experience: foundational skill
      development owing to training in a specialized setting; additional need for
      education and support; unaddressed gaps in pragmatic skills; and uncertainty
      about family physicians' role in palliative care. CONCLUSION: Residents described
      experiences that both supported and inadvertently discouraged them from
      considering future engagement in palliative care. Reassuringly, residents were
      also able to underscore opportunities for improvement in palliative care
      education.

PMID- 27035009
TI  - [Prepared for the moment of discovery--Wilhelm Conrad Rontgen].

PMID- 27035010
TI  - About the usefulness of biology-based models to describe cell   survival after
      exposure to ionizing radiation.

PMID- 27035011
TI  - Technology: Smartphone science.

PMID- 27035013
TI  - Retraction notice to "Antiviral and myocyte protective effects of IL-28A in
      coxsackievirus B3-induced myocarditis" [Braz. J. Infect. Dis. (2015) 132-140].

PMID- 27035012
TI  - Identification of anionic supramolecular complexes of sulfonamide receptors with
      Cl-, NO3-, Br-, and I- by APCI-MS.
AB  - As part of a mass spectrometric investigation of the binding properties of
      sulfonamide anion receptors, an atmospheric pressure chemical ionization mass
      spectrometric (APCI-MS) method involving direct infusion followed by thermal
      desorption was employed for identification of anionic supramolecular complexes in
      dichloromethane (CH2Cl2). Specifically, the dansylamide derivative of tris(2
      aminoethyl)amine (tren) (1), the chiral 1,3-benzenesulfonamide derivatives of
      (1R,2S)-(+)-cis-1-amino-2-indanol (2), and (R)-(+)-bornylamine, (3), were shown
      to bind halide and nitrate ions in the presence of (n-Bu)4N+X- (X- = Cl-, NO3-,
      Br-, I-). Solutions of receptors and anions in CH2Cl2 were combined to form the
      anionic supramolecular complexes, which were subsequently introduced into the
      mass spectrometer via direct infusion followed by thermal desorption. The anionic
      supramolecular complexes [M + X]-, (M = 1-3, X- = Cl-, NO3-, Br-, I-) were
      observed in negative mode APCI-MS along with the deprotonated receptors [M - H]-.
      Full ionization energy of the APCI corona pin (4.5 kV) was necessary for
      obtaining mass spectra with the best signal-to-noise ratios.

PMID- 27035014
TI  - [Contrast radiography of the salivary glands].

PMID- 27035015
TI  - [The history of development of medical information systems].

PMID- 27035016
TI  - Ovarian cancer.

PMID- 27035017
TI  - Response.

PMID- 27035018
TI  - To truly look inside.

PMID- 27035019
TI  - Sam Adjei.

PMID- 27035020
TI  - Progress in electronic medical record adoption in Canada.
AB  - OBJECTIVE: To determine the rate of adoption of electronic medical records (EMRs)
      by physicians across Canada, provincial incentives, and perceived benefits of and
      barriers to EMR adoption. DATA SOURCES: Data on EMR adoption in Canada were
      collected from CINAHL, MEDLINE, PubMed, EMBASE, the Cochrane Library, the Health
      Council of Canada, Canada Health Infoway, government websites, regional EMR
      associations, and health professional association websites. STUDY SELECTION:
      After removal of duplicate articles, 236 documents were found matching the
      original search. After using the filter Canada, 12 documents remained. Additional
      documents were obtained from each province's EMR website and from the Canada
      Health Infoway website. SYNTHESIS: Since 2006, Canadian EMR adoption rates have
      increased from about 20% of practitioners to an estimated 62% of practitioners in
      2013, with substantial regional disparities ranging from roughly 40% of
      physicians in New Brunswick and Quebec to more than 75% of physicians in Alberta.
      Provincial incentives vary widely but appear to have only a weak relationship
      with the rate of adoption. Many adopters use only a fraction of their software's
      available functions. User-cited benefits to adoption include time savings,
      improved record keeping, heightened patient safety, and confidence in retrieved
      data when EMRs are used efficiently. Barriers to adoption include financial and
      time constraints, lack of knowledgeable support personnel, and lack of
      interoperability with hospital and pharmacy systems. CONCLUSION: Canadian
      physicians remain at the stage of EMR adoption. Progression in EMR use requires
      experienced, knowledgeable technical support during implementation, and financial
      support for the transcription of patient data from paper to electronic media. The
      interoperability of EMR offerings for hospitals, pharmacies, and clinics is the
      rate-limiting factor in achieving a unified EMR solution for Canada.

PMID- 27035021
TI  - Study draws attention to missed patient care.

PMID- 27035022
TI  - Pathology and diagnostic cuts spark national debate.

PMID- 27035023
TI  - Queensland cements mandated nurse-to-patient ratios in law.

PMID- 27035024
TI  - New resuscitation guidelines released.

PMID- 27035025
TI  - Report highlights preventable hospitalisations.

PMID- 27035026
TI  - Integrated domestic violence service spared.

PMID- 27035027
TI  - Nurses urged to speak out on problems in aged care.

PMID- 27035028
TI  - Aged Care Complaints Commissioner assumes control.

PMID- 27035029
TI  - Privacy, professionalism and social media.

PMID- 27035030
TI  - Haematological malignancies.

PMID- 27035031
TI  - Respect.

PMID- 27035033
TI  - Unexamined Endocrine Disruption? Pesticides Inhibit Prostaglandin Activity.

PMID- 27035034
TI  - Stepwise Hydration of 2-Aminooxazole: Theoretical Insight into the Structure,
      Finite Temperature Behavior and Proton-Induced Charge Transfer.
AB  - It was recently suggested that 2-aminooxazole (AO) could contribute to the
      formation of RNA nucleotides on primitive earth. In this article we have
      considered by means of computational modeling the influence of microhydration on
      the structural and spectral properties of this potential prebiotic molecule. The
      stable structures of AO(H2O)n were obtained first by sampling the potential
      energy landscapes of clusters containing up to n = 20 water molecules, using a
      simple but reasonably accurate force field and replica-exchange molecular
      dynamics simulations. Through reoptimization using an explicit description of
      electronic structure at the level of density functional theory with the M06-2X
      functional, the formation energies, ionization energies and electron affinities
      were determined in the vertical and adiabatic treatments, as well as vibrational
      and optical spectra covering the far-IR, mid-IR, and lower part of the UV ranges.
      The results generally show a clear segregation between the aminooxazole solute
      and the water molecules, a water cluster being formed near the nitrogen and amino
      group side leaving the hydrocarbon side dry even at temperatures corresponding to
      the liquid state. The spectral signatures generally concur and show distinct
      contributions of the solute and solvent, spectral shifts to lower energies being
      in agreement with earlier calculations in bulk solvent. We have also investigated
      the importance of microhydration on the charge transfer cross section upon
      collision with a proton, thereby extending an earlier investigation on the bare
      AO molecule. The presence of water molecules generally reduces the propensity for
      charge transfer at small sizes, but the influence of the solvent steadily
      decreases in larger droplets. 

PMID- 27035032
TI  - Subtyping of Salmonella enterica Subspecies I Using Single-Nucleotide
      Polymorphisms in Adenylate Cyclase.
AB  - Methods to rapidly identify serotypes of Salmonella enterica subspecies I are of
      vital importance for protecting the safety of food. To supplement the serotyping
      method dkgB-linked intergenic sequence ribotyping (ISR), single-nucleotide
      polymorphisms were characterized within adenylate cyclase (cyaA). The National
      Center for Biotechnology Information (NCBI) database had 378 cyaA sequences from
      S. enterica subspecies I, which included 42 unique DNA sequences and 19 different
      amino acid sequences. Five representative isolates, namely serotypes Typhimurium,
      Kentucky, Enteritidis phage type PT4, and two variants of Enteritidis phage type
      PT13a, were differentiated within a microsphere-based fluidics system in cyaA by
      allele-specific primer extension. Validation against 25 poultry-related
      environmental Salmonella isolates representing 11 serotypes yielded a ~89%
      success rate at identifying the serotype of the isolate, and a different region
      could be targeted to achieve 100%. When coupled with ISR, all serotypes were
      differentiated. Phage lineages of serotype Enteritidis 13a and 4 were identified,
      and a biofilm-forming strain of PT13a was differentiated from a smooth phenotype
      within phage type. Comparative ranking of mutation indices to genes such as the
      tRNA transferases, the diguanylate cyclases, and genes used for multilocus
      sequence typing indicated that cyaA is an appropriate gene for assessing
      epidemiological trends of Salmonella because of its relative stability in
      nucleotide composition.

PMID- 27035035
TI  - Atomic Layer Deposition of Al2O3-Ga2O3 Alloy Coatings for Li[Ni0.5Mn0.3Co0.2]O2
      Cathode to Improve Rate Performance in Li-Ion Battery.
AB  - Metal oxide coatings can improve the electrochemical stability of cathodes and
      hence, their cycle-life in rechargeable batteries. However, such coatings often
      impose an additional electrical and ionic transport resistance to cathode
      surfaces leading to poor charge-discharge capacity at high C-rates. Here, a mixed
      oxide (Al2O3)1-x(Ga2O3)x alloy coating, prepared via atomic layer deposition
      (ALD), on Li[Ni0.5Mn0.3Co0.2]O2 (NMC) cathodes is developed that has increased
      electron conductivity and demonstrated an improved rate performance in comparison
      to uncoated NMC. A "co-pulsing" ALD technique was used which allows intimate and
      controlled ternary mixing of deposited film to obtain nanometer-thick mixed oxide
      coatings. Co-pulsing allows for independent control over film composition and
      thickness in contrast to separate sequential pulsing of the metal sources.
      (Al2O3)1-x(Ga2O3)x alloy coatings were demonstrated to improve the cycle life of
      the battery. Cycle tests show that increasing Al-content in alloy coatings
      increases capacity retention; whereas a mixture of compositions near
      (Al2O3)0.5(Ga2O3)0.5 was found to produce the optimal rate performance.

PMID- 27035037
TI  - Acknowledging and Thanking our Peer Reviewers.

PMID- 27035038
TI  - Leukotriene Receptor Antagonists in the Treatment of Acute Asthma.

PMID- 27035041
TI  - Common Questions About Recurrent Urinary Tract Infections in Women.
AB  - Recurrent urinary tract infections (UTIs) are common in women, including healthy
      women with normal genitourinary anatomy. Recurrent UTI is typically defined as
      three or more UTIs within 12 months, or two or more occurrences within six
      months. The same species that caused previous infections is typically responsible
      for recurrences. In premenopausal women, sexual intercourse three or more times
      per week, spermicide use, new or multiple sex partners, and having a UTI before
      15 years of age are established risk factors. In postmenopausal women, risk is
      primarily increased by sequelae of lower estrogen levels. Episodes of recurrent
      UTI are typically characterized by dysuria and urinary frequency or hesitancy.
      Findings from the history or physical examination that suggest complicated
      infection or another disease process warrant additional evaluation. At least one
      symptomatic episode should be verified by urine culture to confirm the diagnosis
      and guide treatment. Imaging is rarely warranted. Short courses of antibiotics
      are as effective as longer courses. Patient-initiated treatment lowers the cost
      of diagnosis, number of physician visits, and number of symptomatic days compared
      with physician-initiated treatment. It also reduces antibiotic exposure compared
      with antibiotic prophylaxis. Antibiotic prophylaxis effectively limits UTI
      recurrence but increases the risk of antibiotic resistance and adverse effects.
      Cranberry products may reduce recurrent UTIs in premenopausal women, but are less
      effective than antibiotic prophylaxis, and data are conflicting. Optimal dosing
      is unknown. Postmenopausal women with atrophic vaginitis may benefit from topical
      estrogen therapy. 

PMID- 27035042
TI  - Prevention and Treatment of Drowning.
AB  - Nearly 4,000 drowning deaths occur annually in the United States, with drowning
      representing the most common injury-related cause of death in children one to
      four years of age. Drowning is a process that runs the spectrum from brief entry
      of liquid into the airways with subsequent clearance and only minor temporary
      injury, to the prolonged presence of fluid in the lungs leading to lung
      dysfunction, hypoxia, neurologic and cardiac abnormalities, and death. The World
      Health Organization has defined drowning as "the process of experiencing
      respiratory impairment from submersion/immersion in liquid." Terms such as near,
      wet, dry, passive, active, secondary, and silent drowning should no longer be
      used because they are confusing and hinder proper categorization and management.
      The American Heart Association's Revised Utstein Drowning Form and treatment
      guidelines are important in guiding care, disposition, and prognosis. Prompt
      resuscitation at the scene after a shorter duration of submersion is associated
      with better outcomes. Because cardiac arrhythmias due to drowning are almost
      exclusively caused by hypoxia, the resuscitation order prioritizes airway and
      breathing before compressions. Prevention remains the best treatment. Education,
      swimming and water safety lessons, and proper pool fencing are the interventions
      with the highest level of current evidence, especially in children two to four
      years of age. Alcohol use during water activities dramatically increases the risk
      of drowning; therefore, abstinence is recommended for all participants and
      supervisors. 

PMID- 27035043
TI  - Common Questions About Oppositional Defiant Disorder.
AB  - Oppositional defiant disorder (ODD) is a disruptive behavior disorder
      characterized by a pattern of angry or irritable mood, argumentative or defiant
      behavior, or vindictiveness lasting for at least six months. Children and
      adolescents with ODD may have trouble controlling their temper and are often
      disobedient and defiant toward others. There are no tools specifically designed
      for diagnosing ODD, but multiple questionnaires can aid in diagnosis while
      assessing for other psychiatric conditions. ODD is often comorbid with attention
      deficit/hyperactivity disorder, conduct disorder, and mood disorders, including
      anxiety and depression. Behavioral therapy for the child and family members
      improves symptoms of ODD. Medications are not recommended as first-line treatment
      for ODD; however, treatment of comorbid mental health conditions with medications
      often improves ODD symptoms. Adults and adolescents with a history of ODD have a
      greater than 90% chance of being diagnosed with another mental illness in their
      lifetime. They are at high risk of developing social and emotional problems as
      adults, including suicide and substance use disorders. Early intervention seeks
      to prevent the development of conduct disorder, substance abuse, and delinquency
      that can cause lifelong social, occupational, and academic impairments. 

PMID- 27035044
TI  - Nonpharmaceutical Treatment of Anxiety in Institutionalized Older Adults.

PMID- 27035047
TI  - A Fungating Lesion on the Tongue.

PMID- 27035049
TI  - Preventing Drowning: What You Should Know.

PMID- 27035050
TI  - Recurrent Urinary Tract Infections.

PMID- 27035051
TI  - Semiconductor-Electrocatalyst Interfaces: Theory, Experiment, and Applications in
      Photoelectrochemical Water Splitting.
AB  - Light-absorbing semiconductor electrodes coated with electrocatalysts are key
      components of photoelectrochemical energy conversion and storage systems. Efforts
      to optimize these systems have been slowed by an inadequate understanding of the
      semiconductor-electrocatalyst (sem|cat) interface. The sem|cat interface is
      important because it separates and collects photoexcited charge carriers from the
      semiconductor. The photovoltage generated by the interface drives "uphill"
      photochemical reactions, such as water splitting to form hydrogen fuel. Here we
      describe efforts to understand the microscopic processes and materials parameters
      governing interfacial electron transfer between light-absorbing semiconductors,
      electrocatalysts, and solution. We highlight the properties of transition-metal
      oxyhydroxide electrocatalysts, such as Ni(Fe)OOH, because they are the fastest
      oxygen-evolution catalysts known in alkaline media and are (typically) permeable
      to electrolyte. We describe the physics that govern the charge-transfer kinetics
      for different interface types, and show how numerical simulations can explain the
      response of composite systems. Emphasis is placed on "limiting" behavior.
      Electrocatalysts that are permeable to electrolyte form "adaptive" junctions
      where the interface energetics change during operation as charge accumulates in
      the catalyst, but is screened locally by electrolyte ions. Electrocatalysts that
      are dense, and thus impermeable to electrolyte, form buried junctions where the
      interface physics are unchanged during operation. Experiments to directly measure
      the interface behavior and test the theory/simulations are challenging because
      conventional photoelectrochemical techniques do not measure the electrocatalyst
      potential during operation. We developed dual-working-electrode (DWE)
      photoelectrochemistry to address this limitation. A second electrode is attached
      to the catalyst layer to sense or control current/voltage independent from that
      of the semiconductor back ohmic contact. Consistent with simulations, electrolyte
      permeable, redox-active catalysts such as Ni(Fe)OOH form "adaptive" junctions
      where the effective barrier height for electron exchange depends on the potential
      of the catalyst. This is in contrast to sem|cat interfaces with dense electrolyte
      impermeable catalysts, such as nanocrystalline IrOx, that behave like solid-state
      buried (Schottky-like) junctions. These results elucidate a design principle for
      catalyzed photoelectrodes. The buried heterojunctions formed by dense catalysts
      are often limited by Fermi-level pinning and low photovoltages. Catalysts
      deposited by "soft" methods, such as electrodeposition, form adaptive junctions
      that tend to provide larger photovoltages and efficiencies. We also preview
      efforts to improve theory/simulations to account for the presence of surface
      states and discuss the prospect of carrier-selective catalyst contacts. 

PMID- 27035052
TI  - Stable isotope probing with 18O-water to investigate microbial growth and death
      in environmental samples.
AB  - Growth and mortality of microorganisms have been characterized through DNA stable
      isotope probing (SIP) with 18O-water in soils from a range of ecosystems.
      Conventional SIP has been improved by sequencing a marker gene in all fractions
      retrieved from an ultracentrifuge tube to produce taxon density curves, which
      allow estimating the atom percent isotope composition of each microbial taxon's
      genome. Very recent advances in SIP with 18O-water include expansion of the
      technique to aquatic samples, investigations of microbial turnover in soil, and
      the first use of 18O-water in RNA-SIP studies.

PMID- 27035053
TI  - Asymmetric Total Synthesis of Sarpagine-Related Indole Alkaloids
      Hydroxygardnerine, Hydroxygardnutine, Gardnerine, (E)-16-epi-Normacusine B, and
      Koumine.
AB  - Sarpagine-related indole alkaloids (-)-hydroxygardnerine, (+)-hydroxygardnutine,
      (-)-gardnerine, (+)-(E)-16-epi-normacusine B, and (-)-koumine were divergently
      synthesized via a common intermediate possessing a piperidine ring with an
      exocyclic (E)-ethylidene side chain, which was constructed by a gold(I)-catalyzed
      6-exo-dig cyclization strategy. 

PMID- 27035054
TI  - Comment on "Optimal Exposure Biomarkers for Nonpersistent Chemicals in
      Environmental Epidemiology".

PMID- 27035055
TI  - Presentation with gastrointestinal symptoms and high case fatality associated
      with group W meningococcal disease (MenW) in teenagers, England, July 2015 to
      January 2016.
AB  - Atypical clinical presentations associated with group W meningococcal disease
      (MenW) are well-described and include pneumonia, septic arthritis, endocarditis
      and epiglottitis/supraglottitis. Following anecdotal reports of teenagers
      presenting with predominantly gastrointestinal symptoms, we undertook a case
      review of MenW cases in 15 to 19 year-olds diagnosed in England between July 2015
      and January 2016. Of the 15 cases, seven presented with a short history of
      nausea, vomiting and diarrhoea; five of these seven cases died within 24 hours of
      presentation to hospital. 

PMID- 27035056
TI  - pH Dependence of Adsorbed Fibrinogen Conformation and Its Effect on Platelet
      Adhesion.
AB  - Quartz crystal microbalance with dissipation (QCM-D) and dual polarization
      interferometry (DPI) were used to investigate fibrinogen (Fib) adsorption
      behavior on different surfaces by changing the pH value. Moreover, integrin
      adhesion to the adsorbed Fibs was studied using DPI. Qualitative and quantitative
      studies of platelet adhesion to the adsorbed Fibs were performed using scanning
      electron microscopy (SEM), confocal laser scanning microscope (CLSM), and
      released lactate dehydrogenase (LDH) assay. Experimental results indicated that
      the conformation and orientation of the absorbed Fibs depended on surface
      property and pH cycling. For the hydrophilic surface, Fibs adsorbed at pH 7.4 and
      presented a alphaC-hidden orientation. As a result, no integrin adhesion was
      observed, and a small number of platelets were adhered because the alphaC-domains
      were hidden under the Fib molecule. By changing the rinsing solution pH from 7.4
      to 3.2 and then back to 7.4, the adsorbed Fib orientation became alphaC-exposed
      via the transformation of Fib conformation during pH cycling. Therefore, integrin
      adhesion was more likely to occur, and more platelets were adhered and activated.
      For the hydrophobic surface, the adsorbed Fibs became more spread and stretched
      due to the strong interaction between the Fibs and surface. alphaC-exposed
      orientation remained unchanged when the rinsing solution pH changed from 7.4 to
      3.2 and then back to 7.4. Therefore, a large number of integrins and platelets
      were adhered to the adsorbed Fibs, and almost all of the adhered platelets were
      activated.

PMID- 27035057
TI  - Lithium Enolates Derived from Pyroglutaminol: Aggregation, Solvation, and
      Atropisomerism.
AB  - Lithium enolates derived from protected pyroglutaminols were characterized by
      using (6)Li, (13)C, and (19)F NMR spectroscopies in conjunction with the method
      of continuous variations. Mixtures of tetrasolvated dimers and tetrasolvated
      tetramers in different proportions depend on the steric demands of the hemiaminal
      protecting group, tetrahydrofuran concentration, and the presence or absence of
      an alpha-fluoro moiety. The high steric demands of the substituted bicyclo[3.3.0]
      ring system promote dimers to an unusual extent and allow solvents and
      atropisomers in cubic tetramers to be observed in the slow-exchange limit.
      Pyridine used as a (6)Li chemical shift reagent proved useful in assigning
      solvation numbers.

PMID- 27035058
TI  - Observational Evidence for Buprenorphine's Impact on Posttraumatic Stress
      Symptoms in Veterans With Chronic Pain and Opioid Use Disorder.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD), chronic pain, and substance use
      disorders are prevalent co-occurring conditions that are challenging to treat
      individually, and there is no evidence-based treatment for all 3. Buprenorphine,
      used to treat opioid use disorder and chronic pain, is a partial nociceptin
      opioid receptor agonist. In preclinical studies, a nociceptin opioid receptor
      agonist was shown to mitigate PTSD symptoms in acute trauma. We compared
      buprenorphine to other opioid medications in its impact on PTSD symptoms in
      patients with chronic pain and opioid and/or other substance use disorders.
      METHOD: We assembled a retrospective cohort of 382 Iraq and Afghanistan veterans
      in US Department of Veterans Affairs health care from October 1, 2007, to July
      29, 2013, with ICD-9-CM diagnoses of PTSD, chronic pain, and substance use
      disorders. We used time-varying general estimating equation models to assess the
      primary outcome, which was change in PTSD symptoms (measured using the PTSD
      Checklist and the Primary Care PTSD Screen) among veterans initiated on
      sublingual buprenorphine versus those maintained on moderately high-dose opioid
      therapy. RESULTS: Twice as many veterans in the buprenorphine group (23.7%)
      compared to those in the opioid therapy group (11.7%) experienced improvement in
      PTSD symptoms (P = .001). Compared to veterans in the opioid therapy group,
      veterans receiving buprenorphine showed significant improvement in PTSD symptoms
      after 8 months, with increasing improvement up to 24 months (incidence rate ratio
      = 1.79; 95% CI, 1.16-2.77; P = .009). There were no differences in the
      longitudinal course of pain ratings between groups. CONCLUSIONS: This
      observational study is the first to report an incidental effect of buprenorphine
      compared to opioid therapy in improving PTSD symptoms in veterans.

PMID- 27035059
TI  - Impact of the Type I Interferon Receptor on the Global Gene Expression Program
      During the Course of Dendritic Cell Maturation Induced by Polyinosinic
      Polycytidylic Acid.
AB  - Dendritic cell (DC) maturation involves widespread changes in cellular function
      and gene expression. The regulatory role of IFNAR in the program of DC maturation
      remains incompletely defined. Thus, the time evolution impact of IFNAR on this
      process was evaluated. Changes in DC phenotype, function, and gene expression
      induced by poly I:C were measured in wild-type and IFNAR(-/-) DC at 9 time points
      over 24 h. Temporal gene expression profiles were filtered on consistency and
      response magnitude across replicates. The number of genes whose expression was
      altered by poly I:C treatment was greatly reduced in IFNAR(-/-) DC, including the
      majority of the downregulated gene expression program previously observed in wild
      type (WT) DC. Furthermore, the number of genes upregulated was almost equal
      between WT and IFNAR(-/-) DC, yet the identities of those genes were distinct.
      Integrating these data with protein-protein interaction data revealed several
      novel subnetworks active during maturation, including nucleotide synthesis,
      metabolism, and repair. A subnetwork associated with redox activity was uniquely
      identified in IFNAR(-/-) DC. Overall, temporal gene expression and network
      analyses identified many genes regulated by the type I interferon response and
      revealed previously unidentified aspects of the DC maturation process.

PMID- 27035060
TI  - Maximum Standardized Uptake Value of (99m)Tc Hydroxymethylene Diphosphonate
      SPECT/CT for the Evaluation of Temporomandibular Joint Disorder.
AB  - Purpose To evaluate the diagnostic accuracy of the quantitative parameter
      standardized uptake value (SUV) at single photon emission computed tomography
      (SPECT)/computed tomography (CT) for the evaluation of temporomandibular joint
      (TMJ) disorder (TMD). Materials and Methods This study was approved by the
      institutional review board, and the need for informed consent was waived. Forty
      four TMJs in 22 patients with TMD (five men and 17 women; mean age +/- standard
      deviation, 30.0 years +/- 12.1) were evaluated. The patients underwent planar
      bone scintigraphy and SPECT/CT 3-4 hours after injection of technetium 99m
      hydroxymethylene diphosphonate. The planar scintigraphy parameter of relative
      ratio (RR) and SPECT/CT parameters mean SUV (SUVmean) and maximum SUV (SUVmax)
      were compared for the visual assessment of TMD on planar scintigraphy images and
      for the presence of TMJ arthralgia. Group comparisons, receiver operating
      characteristic analysis, and Pearson correlation analysis were conducted. Results
      SUVmax gradually increased from normal (2.82 +/- 0.73) to mild or moderately
      abnormal (3.56 +/- 0.76, P < .05) and then to severely abnormal (4.86 +/- 1.25, P
      < .05). However, RR and SUVmean did not vary significantly according to visual
      grade (P > .05). On the other hand, SUVmax was significantly greater in
      arthralgic TMJs (4.15 +/- 1.11) than in nonarthralgic TMJs (2.97 +/- 0.75, P <
      .001), as was SUVmean (1.63 +/- 0.42 vs 1.30 +/- 0.31, respectively; P = .005).
      However, there was no significant difference in RR (3.61 +/- 0.57 vs 3.76 +/-
      0.68, P = .45). In receiver operating characteristic curve analyses for
      arthralgic TMJ, SUVmax had the greatest area under the curve (area of 0.815).
      Conclusion SUVmax derived from bone SPECT/CT may be useful for the evaluation of
      TMD. ((c)) RSNA, 2016 Online supplemental material is available for this article.

PMID- 27035061
TI  - Postoperative infections after IntraSPINE(r) implantation surgery.

PMID- 27035062
TI  - Brain metabolite levels in recently sober individuals with alcohol use disorder:
      Relation to drinking variables and relapse.
AB  - Magnetic resonance spectroscopy (MRS) studies in alcohol use disorder (AUD)
      typically report lower levels of N-acetylaspartate (NAA) and choline-containing
      compounds (Cho) in several brain regions. Metabolite levels, however, are labile
      and can be affected by several competing factors, some related to drinking
      variables.. This in vivo MRS study included 20 recently sober (19.6+/-12.6 days)
      individuals with AUD and 15 controls. MRS was performed in single voxels placed
      in frontal white matter and thalamic regions using Constant-Time Point Resolved
      Spectroscopy (CT-PRESS) for absolute quantification of NAA, Cho, total creatine
      (tCr), and glutamate (Glu). A trend toward a thalamic NAA deficit in the total
      AUD group compared with controls was attributable to the subgroup of alcoholics
      who relapsed 3 or so months after scanning. In the total AUD group, frontal and
      thalamic NAA and Cho levels were lower with more recent drinking; frontal and
      thalamic Cho levels were also lower in AUD individuals with past stimulant abuse.
      Thalamic Cho levels were higher in binge-drinking AUD individuals and in those
      with longer length of alcohol dependence. MRS-visible metabolite peaks appear to
      be modulated by variables related to drinking behaviors, suggesting a sensitivity
      of MRS in tracking and predicting the dynamic course of alcoholism.

PMID- 27035063
TI  - Amygdala volume is reduced in early course schizophrenia.
AB  - Subcortical structural alterations have been implicated in the neuropathology of
      schizophrenia. Yet, the extent of anatomical alterations for subcortical
      structures across illness phases remains unknown. To assess this, magnetic
      resonance imaging (MRI) was used to examine volume differences of major
      subcortical structures: thalamus, nucleus accumbens, caudate, putamen, globus
      pallidus, amygdala and hippocampus. These differences were examined across four
      groups: (i) healthy comparison subjects (HCS, n=96); (ii) individuals at high
      risk (HR, n=21) for schizophrenia; (iii) early-course schizophrenia patients (EC
      SCZ, n=28); and (iv) chronic schizophrenia patients (C-SCZ, n=20). Raw gray
      matter volumes and volumetric ratios (volume of specific structure/total gray
      matter volume) were extracted using automated segmentation tools. EC-SCZ group
      exhibited smaller bilateral amygdala volumetric ratios, compared to HCS and HR
      subjects. Findings did not change when corrected for age, level of education and
      medication use. Amygdala raw volumes did not differ among groups once adjusted
      for multiple comparisons, but the smaller amygdala volumetric ratio in EC-SCZ
      survived Bonferroni correction. Other structures were not different across the
      groups following Bonferroni correction. Smaller amygdala volumes during early
      illness course may reflect pathophysiologic changes specific to illness
      development, including disrupted salience processing and acute stress responses.

PMID- 27035064
TI  - Antihyperalgesic effect of [(+/-)-(2,4,6-cis)-4-chloro-6-(naphthalen-1-yl)
      tetrahydro-2H-pyran-2-yl]methanol: participation of the NO/cGMP/KATP pathway and
      kappa-opioid receptor.
AB  - The present study used behavioral analyses to investigate the involvement of the
      NO/cGMP/KATP pathway, serotoninergic, and opioid systems in the antinociceptive
      action of [(+/-)-(2,4,6-cis)-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2
      yl]methanol (CTHP) in mice. Oral administration of CTHP (1, 5, 10, and 30 mg/kg)
      exerted effects at higher doses in chemical models of nociception (the acetic
      acid writhing and formalin tests) as well as a thermal model (the tail-flick
      test). It was also found that pretreatment with L-N-nitroarginine methyl ester
      (nonselective nitric oxide synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (selective inhibitor of nitric oxide-sensitive guanosyl
      cyclase), glibenclamide (selective ATP-sensitive K channel blocker), naloxone
      (nonselective opioid receptor blocker), and nor-binaltorphimine (selective kappa
      opioid receptor blocker), but not methylnaltrexone (peripheral MU-opioid receptor
      blocker) or naltrindole (selective delta-opioid receptor blocker), reversed the
      antinociceptive effect of CTHP. In addition, CTHP induced the development of
      tolerance in the tail-flick test: the tolerance appeared later compared with
      morphine, and was only observed with a higher dose. Taken together, the present
      study showed that the systemic administration of CTHP reduced pain induced by
      chemical and thermal stimuli. We also suggest that the possible mechanisms
      include the involvement of the NO/cGMP/KATP pathway and the kappa-opioid
      receptor.

PMID- 27035065
TI  - Effect of ketamine administration, alone and in combination with E-6837, on
      climbing behavior.
AB  - Some types of schizophrenia have been associated with repetitive movements
      lacking specific purpose, also known as stereotyped behavior. Dopamine agonists
      (D2) and noncompetitive N-methyl-D-aspartate receptor antagonists (e.g. ketamine)
      have been administered in rodent models to induce stereotyped behavior that
      resembles some motor symptoms of schizophrenia. Recently, a relationship has been
      found between 5-HT6 receptors (5-HT6Rs) and dopaminergic activity. The present
      study evaluates the effect of ketamine (5 and 10 mg/kg), alone and in combination
      with the 5-HT6R agonist E-6837, on the climbing behavior of male mice. Ketamine
      was administered with an acute (1 day) and subchronic (5 day) scheme. Later,
      these doses and schemes were combined with an acute scheme of E-6837 (5 and 10
      mg/kg). With both the acute and the subchronic schemes, ketamine increased
      climbing behavior at a dose of 10 mg/kg, and this effect was reversed by E-6837
      (at 5 and 10 mg/kg). The present results suggest that there is an interaction
      between N-methyl-D-aspartate and 5-HT6 receptors in the regulation of climbing
      behavior. Further research is necessary to provide more evidence on this
      interaction.

PMID- 27035066
TI  - Enhancement of fengycin production in Bacillus amyloliquefaciens by genome
      shuffling and relative gene expression analysis using RT-PCR.
AB  - Genome shuffling is an efficient approach for the rapid engineering of microbial
      strains with desirable industrial phenotypes. In this study, we used genome
      shuffling in an attempt to improve fengycin production of the wild-type strain
      Bacillus amyloliquefaciens ES-2-4. After 2 rounds of genome shuffling, a high
      yield recombinant F2-72 (FMB72) strain that exhibited 8.30-fold increases in
      fengycin production was obtained. Comparative analysis of synthetase gene (fenA)
      expression was conducted between the initial and shuffled strains using
      fluorescent quantitation RT-PCR. Delta CT (threshold cycle) relative quantitation
      analysis revealed that fengycin synthetase gene (fenA) expression at the
      transcriptional level in the FMB72 strain was 12.77-fold greater than in the ES-2
      4 wild type. The shuffled strain has a potential application in food and
      pharmaceutical industries. At the same time, the analysis of improved phenotypes
      will provide more valuable data for inverse metabolic engineering. 

PMID- 27035068
TI  - Erratum: Cigarette Smoke-Induced Damage-Associated Molecular Pattern Release from
      Necrotic Neutrophils Triggers Proinflammatory Mediator Release.

PMID- 27035067
TI  - Ivacaftor-Induced Proteomic Changes Suggest Monocyte Defects May Contribute to
      the Pathogenesis of Cystic Fibrosis.

PMID- 27035069
TI  - Erratum: Aberrant DNA Methylation of Phosphodiesterase 4D Alters Airway Smooth
      Muscle Cell Phenotypes.

PMID- 27035072
TI  - Fused imidazoles as potential chemical scaffolds for inhibition of heat shock
      protein 70 and induction of apoptosis. Synthesis and biological evaluation of
      phenanthro[9,10-d]imidazoles and imidazo[4,5-f][1,10]phenanthrolines.
AB  - The imidazole ring is widespread in biologically active compounds, and hence
      imidazole-containing scaffolds are useful starting points for drug discovery
      programmes. We report the synthesis of a series of novel imidazole-containing
      compounds fused with either phenanthrene or phenanthroline, which show enhanced
      growth inhibitory potency against human colon, breast and melanoma cancer cell
      lines, as well as evidence of inhibition of the molecular chaperone heat shock
      protein 70 (Hsp70) pathway in cells, as shown by depletion of downstream
      oncogenic client proteins of the Hsp90 chaperone pathway, and induction of
      apoptosis. 

PMID- 27035071
TI  - The effect of NOD2 on the microbiota in Crohn's disease.
AB  - Recent advancements toward the treatment of Crohn's disease (CD) indicate great
      promise for long-term remission. CD patients suffer from a complex host of
      dysregulated interactions between their innate immune system and microbiome. The
      most predominant link to the onset of CD is a genetic mutation in the innate
      immune receptor nucleotide-binding oligomerization domain-containing 2 (NOD2).
      NOD2 responds to the presence of bacteria and stimulates the immune response.
      Mutations to NOD2 promote low diversity and dysbiosis in the microbiome, leading
      to impaired mucosal barrier function. Current treatments suppress the immune
      response rather than enhancing the function of this critical protein. New
      progress toward stabilizing NOD2 signaling through its interactions with
      chaperone proteins holds potential in the development of novel CD therapeutics.

PMID- 27035073
TI  - Change in employment status in bipolar disorder: a longitudinal study using
      national claims data.
AB  - OBJECTIVE: To assess change in employment status in patients with bipolar
      disorder in comparison with non-mentally ill controls from 1 year before bipolar
      incidence to 10 years after. Sociodemographic factors of change in employment
      status were also examined for patients with bipolar disorder. METHOD: A cohort of
      502 patients with ICD-9-CM bipolar disorder was identified using claims data from
      the National Health Insurance Research Database of Taiwan between 1998 and 2001
      and compared to non-mentally ill controls through December 31, 2008. The primary
      outcome measure was the time from bipolar incidence to the time of change in
      employment status, ie, from earning income to not earning income. RESULTS: The
      probability of changing to a non-income earner was significantly higher (P <
      .0001) in patients with bipolar disorder than in controls over time, even before
      the incidence of bipolar disorder (27% vs 14% for patients with bipolar disorder
      vs controls, respectively). Risks of occupational deterioration in patients with
      bipolar disorder were greater in the year before incidence and in the following
      year, with gradually decreasing risks over the subsequent 2 years, and comparable
      to controls from the third year onward. The adjusted hazard ratio of changing to
      a non-income earner was 2.06 (95% CI, 1.82-2.33) in patients with bipolar
      disorder. Male sex, ages 18 to 25 years, lower payroll bracket (< NT$50,001 [US
      $1,489]), and living in an urban area and insured area in the Northern region
      were associated with the risk of changing to a non-income earner in patients with
      bipolar disorder. CONCLUSIONS: Patients with bipolar disorder had poorer
      employment outcomes than the controls, with greater risks of occupational
      deterioration before and after the bipolar episodes. Employment status should be
      incorporated as a measure of functioning and of treatment and intervention
      effectiveness in clinical practices and research.

PMID- 27035074
TI  - Femtosecond laser-assisted keratotomy.
AB  - PURPOSE OF REVIEW: To review the recent literature on femtosecond laser-assisted
      astigmatic keratotomy and its applications to naturally occurring as well as
      postoperative astigmatism in multiple settings. RECENT FINDINGS: Femtosecond
      laser technology has improved the safety and efficacy of astigmatic keratotomy in
      the treatment of astigmatism. Intrastromal femtosecond astigmatic keratotomy
      (ISAK) may have even lower complication rates, though long-term results are still
      being established. Femtosecond laser-assisted keratotomy (FSAK) in the surgical
      setting, such as at the time of or after cataract surgery, keratoplasty, and
      glaucoma surgery, has been investigated with overall good results. There have
      been some reports of overcorrection and undercorrection of astigmatism,
      particularly in the setting of high and nonorthogonal astigmatism. Further
      refinement of nomograms in these settings is indicated. Complications such as
      full thickness FSAK and ISAK incisions are rare but have been reported, and may
      be mitigated by the integration of dynamic optical coherence tomography (OCT)
      into femtosecond laser systems. SUMMARY: FSAK is an effective and safe way to
      correct astigmatism. These procedures have some advantages over manual astigmatic
      keratotomy, including increased accuracy of incision depth and placement. As
      nomograms are refined and technologies such as dynamic OCT are further
      incorporated into femtosecond systems, results are likely to continue improving.

PMID- 27035075
TI  - An update on new low add multifocal intraocular lenses.
AB  - PURPOSE OF REVIEW: The purpose of this article is to provide an overview and
      update on recent literature regarding low-add multifocal intraocular lenses
      (MFIOLs). RECENT FINDINGS: Clinical and benchwork studies involving low-add
      MFIOLs were reviewed. Clinical studies focused on uncorrected distance,
      intermediate, and near vision, along with secondary dysphotopsias. Studies done
      in the laboratory assessed the optical properties of various lenses, and
      optically replicated visual scenarios at different viewing distances. SUMMARY:
      MFIOLs continue to evolve to meet the needs of an evolving patient population.
      Low-add MFIOLs have been shown to improve intermediate vision, while not
      compromising distance vision, along with decreasing dysphotopsias. Their optical
      properties continue to be optimized, and with these new improvements, larger
      groups of patients can benefit from the range of vision provided. It is important
      to understand the strengths and limitations of these new MFIOLs, this review
      provided the most up to date review of the literature describing low-add MFIOLs.
      The new information provided by these reviewed articles allows the
      ophthalmologist to provide the best options for each individual patient.

PMID- 27035076
TI  - Breast cancer upregulating genes in stromal cells by LINE-1 hypermethylation and
      micrometastatic detection.
AB  - Changes in the methylation level of genes containing LINE-1 alter host gene
      regulation. AIM: This study demonstrates that paracrine signaling of breast
      cancer influences the epigenetic regulation of stromal cells. METHODS: We proved
      in vitro and in vivo breast cancer promoted LINE-1 methylation exists exclusively
      in female stromal cells. RESULTS: Genes containing LINE-1 of breast cancer
      stromal cells were upregulated. Furthermore, one of the genes, MUC-1, was
      demonstrated to have expression in plasma cells from the lymph nodes of patients
      with lymph node metastasis or micrometastasis. CONCLUSION: Breast cancer sends a
      paracrine signal to stroma cells causing LINE-1 epigenetic regulation. Moreover,
      the regulated genes in stroma cells are potential biomarkers for detecting breast
      cancer micrometastasis.

PMID- 27035077
TI  - Mixed Cryoglobulin-induced Esophageal Necrosis in a Patient With Hepatitis C.

PMID- 27035078
TI  - An Unexpected Pulmonary Complication Following Transcatheter Arterial
      Chemoembolization of a Small Hepatocellular Carcinoma.

PMID- 27035079
TI  - Palliative Locoregional Treatment for Unresectable Nonmetastatic Klatskin Tumor:
      Percutaneous Transhepatic Biliary Drainage Combined With 3-dimensional Conformal
      Radiotherapy.
AB  - PURPOSE: This study aimed to identify the effect of percutaneous transhepatic
      biliary drainage (PTBD) combined with 3-dimensional conformal radiotherapy (3D
      CRT) in comparison with PTBD therapy only on the treatment of unresectable
      Klatskin tumors (KTs). MATERIALS AND METHODS: Thirty-seven patients with
      unresectable KTs were included in the study. Twenty-six patients received PTBD
      and 3D-CRT successively, whereas the other 11 patients received PTBD only.
      Changes in the clinical symptoms after the PTBD treatment, the radiotherapy
      effect, and the survival time were recorded and analyzed. RESULTS: The clinical
      symptoms of the 2 groups gradually decreased after the PTBD treatment. The
      radiotherapy effect showed an overall effective rate (complete response+partial
      response) of 17 (65.38%), and the serum carbohydrate antigen-19-9 levels before
      and after 3D-CRT were significantly different (P<0.001). The mean survival time
      of the PTBD group was 11.27 months; the 1- and 2-year cumulative survival rates
      were 36.4% and 9.1%, respectively. The mean survival time of the combined therapy
      group was 22.77 months; the 1-, 2-, and 3-year cumulative survival rates were
      53.8%, 38.5%, and 11.5%, respectively. The log-rank test showed that the patients
      who received combined therapy had longer survival time than the patients who only
      received PTBD (P=0.001). CONCLUSIONS: Patients with unresectable KTs who
      underwent PTBD could relieve biliary obstruction effectively. Although this study
      is not a randomized trial, 3D-CRT combined with PTBD seems to be a promising and
      an effective method as a palliative treatment for unresectable KTs.

PMID- 27035080
TI  - Digital Chromoendoscopy With i-Scan for In Vivo Prediction of Advanced Colorectal
      Neoplasia: A Multicenter Study.
AB  - BACKGROUND: Recent studies have analyzed the potential of advanced endoscopic
      imaging techniques for differentiating hyperplastic and adenomatous colorectal
      lesions. Latest endoscopic resection techniques now also allow for treatment of
      more advanced staged lesions including treatment of early cancerous lesions.
      AIMS: To assess the potential of the i-scan technology to differentiate between
      adenomatous polyps and advanced staged neoplasia. METHODS: Consecutive patients
      undergoing colonoscopy at a tertiary referral center were included. After a
      dedicated training, participating endoscopists underwent a review of 298 unknown
      images of colonic lesions to assess colorectal lesion histology. RESULTS: Overall
      accuracy for prediction of advanced staged neoplasia was 92.2% (sensitivity:
      94.2%, specificity 90.9%). The positive and negative predictive values were
      calculated as 87.5% and 95.9%, respectively. The kappa-value for differentiating
      adenomatous polyps and advanced staged neoplasia was 0.8193 (0.7894 to 0.8492).
      Intraobserver agreement was calculated with a kappa-value of 0.9301 (0.8875 to
      0.9727). CONCLUSIONS: Accurate interpretation of i-scan images for prediction of
      advanced colorectal neoplasia can successfully be performed even by nonexpert
      endoscopists with a high overall accuracy and excellent interobserver agreements.

PMID- 27035081
TI  - Integrative Medicine and Case Management.
AB  - The evolution of the integration of health care modalities has changed. The
      National Institutes of Health founded office of the National Center for
      Complementary and Alternative Medicine in the early 1990s to investigate
      integrative therapies through scientific research. In December 2014, the name and
      mission were updated to the National Center for Complementary and Integrative
      Health. Case managers, the coordinators of health care, must understand the
      changes to "integrative medicine" and the allure of the alternative modalities. 

PMID- 27035082
TI  - The New Age of Bullying and Violence in Health Care: Part 2: Advancing
      Professional Education, Practice Culture, and Advocacy.
AB  - PURPOSE AND OBJECTIVES: This article will discuss new regulations and
      professional guidance addressing bullying and workplace violence including
      addressing recent organizational initiatives to support the health care
      workforce; reviewing how professional education has historically contributed to a
      culture of bullying across health care; and exploring how academia is shifting
      the culture of professional practice through innovative education programming.
      PRIMARY PRACTICE SETTINGS(S): Applicable to all health care sectors where case
      management is practiced. FINDINGS/CONCLUSION: This article is the second of two
      on this topic. Part 2 focuses on how traditional professional education has been
      cited as a contributing factor to bullying within and across disciplines. Changes
      to educational programming will impact the practice culture by enhancing
      collaboration and meaningful interactions across the workforce. Attention is also
      given to the latest regulations, professional guidelines, and organizational
      initiatives. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Workplace bullying and
      violence have contributed to health care become the most dangerous workplace
      sector. This is a concerning issue that warrants serious attention by all
      industry stakeholders.Traditional professional education models have created a
      practice culture that promotes more than hinders workplace bullying and violence
      in the industry. Changes to both academic coursework and curricula have shifted
      these antiquated practice paradigms across disciplines. New care delivery modes
      and models have fostered innovative care and treatment perspectives. Case
      management is poised to facilitate the implementation of these perspectives and
      further efforts to promote a safe health care workplace for patients and
      practitioners alike.

PMID- 27035083
TI  - Predicting Adverse Outcomes After Discharge From Complex Continuing Care Hospital
      Settings to the Community.
AB  - PURPOSE OF STUDY: The purpose was to identify risk and protective factors
      assessed at complex continuing care (CCC) admission that were associated with
      three adverse outcomes (death, readmission, and incidence of or failure to
      improve possible depression) for persons discharged from CCC to the community
      with home care services. PRIMARY PRACTICE SETTINGS: CCC, home care, community.
      METHODOLOGY AND SAMPLE: The sample included all CCC patients in Ontario assessed
      with the Resident Assessment Instrument-Minimum Data Set 2.0 between January 2003
      and December 2010 and who were subsequently assessed with the Resident Assessment
      Instrument-Home Care within 6 months of discharge to the community (n = 9,940).
      Separate multivariable logistic regression models were developed for each
      outcome. RESULTS: Within 6 months, 4.9% of the sample had died, 6.5% were
      readmitted to any Ontario CCC facility, and 13.7% showed symptoms of new possible
      depression or failure to improve possible depression. Heart failure, chronic
      obstructive pulmonary disease (COPD), health instability, intravenous/tube feed,
      and pressure ulcer were associated with increased risk of death. Difficulty with
      comprehension, possible depression, COPD, unstable conditions, acute episode or
      flare-up, short-term prognosis, worsening self-sufficiency, and having either
      patient or caregiver optimistic about discharge were associated with increased
      risk of readmission. Existing depressive symptoms or depression, unsettled
      relationships, multimorbidity, and polypharmacy were associated with risk for
      incidence of or failure to improve possible depression. Optimism about
      rehabilitation potential and high social engagement were protective against
      readmission and depressive outcomes, respectively. IMPLICATIONS FOR CASE
      MANAGEMENT PRACTICE: Person-level clinical data collected on admission to CCC can
      be used to identify high-risk patients and trigger early discharge planning
      processes and other in-home interventions. These results support the sharing of
      information between settings, and highlight key areas in which care teams in CCC
      and case managers in home care organizations can work together to support the
      transition to home and potentially reduce adverse postdischarge outcomes.

PMID- 27035084
TI  - Disease Management, Case Management, Care Management, and Care Coordination: A
      Framework and a Brief Manual for Care Programs and Staff.
AB  - With the changing landscape of health care delivery in the United States since
      the passage of the Patient Protection and Affordable Care Act in 2010, health
      care organizations have struggled to keep pace with the evolving paradigm,
      particularly as it pertains to population health management. New nomenclature
      emerged to describe components of the new environment, and familiar words were
      put to use in an entirely different context. PURPOSE/OBJECTIVES: This article
      proposes a working framework for activities performed in case management, disease
      management, care management, and care coordination. The author offers standard
      working definitions for some of the most frequently used words in the health care
      industry with the goal of increasing consistency for their use, especially in the
      backdrop of the Centers for Medicaid & Medicare Services offering a "chronic case
      management fee" to primary care providers for managing the sickest, high-cost
      Medicare patients. PRIMARY PRACTICE SETTINGS: Health care organizations
      performing case management, care management, disease management, and care
      coordination. FINDINGS/CONCLUSIONS: Road map for consistency among users, in
      reporting, comparison, and for success of care management/coordination programs.
      IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This article offers a working
      framework for disease managers, case and care managers, and care coordinators. It
      suggests standard definitions to use for disease management, case management,
      care management, and care coordination. Moreover, the use of clear terminology
      will facilitate comparing, contrasting, and evaluating all care programs and
      increase consistency. The article can improve understanding of care program
      components and success factors, estimate program value and effectiveness,
      heighten awareness of consumer engagement tools, recognize current state and
      challenges for care programs, understand the role of health information
      technology solutions in care programs, and use information and knowledge gained
      to assess and improve care programs to design the "next generation" of programs.

PMID- 27035085
TI  - The Dignified Passing.

PMID- 27035086
TI  - Engaging the LBGT Patient: The Medical/Legal Landscape.

PMID- 27035087
TI  - End-of-Life Discussions: A Tool for the "Difficult Conversations".

PMID- 27035088
TI  - Reducing Disparities in the LGBT Community.

PMID- 27035091
TI  - SrMnO3 Thermochromic Behavior Governed by Size-Dependent Structural Distortions.
AB  - The influence of particle size in both the structure and thermochromic behavior
      of 4H-SrMnO3 related perovskite is described. Microsized SrMnO3 suffers a
      structural transition from hexagonal (P63/mmc) to orthorhombic (C2221) symmetry
      at temperature close to 340 K. The orthorhombic distortion is due to the tilting
      of the corner-sharing Mn2O9 units building the 4H structural type. When
      temperature decreases, the distortion becomes sharper reaching its maximal degree
      at ~125 K. These structural changes promote the modification of the electronic
      structure of orthorhombic SrMnO3 phase originating the observed color change.
      nano-SrMnO3 adopts the ideal 4H hexagonal structure at room temperature, the
      orthorhombic distortion being only detected at temperature below 170 K. A
      decrease in the orthorhombic distortion degree, compared to that observed in the
      microsample, may be the reason why a color change is not observed at low
      temperature (77 K). 

PMID- 27035092
TI  - Overexpression of long non-coding RNA-CTD903 inhibits colorectal cancer invasion
      and migration by repressing Wnt/beta-catenin signaling and predicts favorable
      prognosis.
AB  - Accumulating evidence reveals that long non-coding RNA (lncRNA) is essential for
      tumorigenesis and progression, but little is known about its roles and mechanisms
      in metastatic colorectal cancer (CRC). This study aimed to detect expression
      level and prognostic role of lncRNA-CTD903 in CRC patients, which was selected
      based on one microarray data. The effects on cell invasion, migration and
      proliferation were investigated after silencing or overexpression of CTD903 in
      CRC cell lines. We also observed the EMT (epithelial-mesenchymal transition)
      phenomenon and effect on cell adhesion. The associations between CTD903 and EMT
      markers, such as E-cadherin, N-cadherin, beta-catenin, ZEB1, ZO-1, Snail, and
      Twist, were determined by western blotting. Our results showed lncRNA-CTD903
      expression was strongly upregulated in 115 CRC patients, comparing to adjacent
      normal tissues. CTD903 was proven to be an independent predicted factor of
      favorable prognosis in CRC patients by using multivariate Cox proportional
      hazards model. After knockdown of CTD903 in RKO and SW480, both cell invasion and
      migration increased, and cells exhibited EMT-like appearance, along with reduced
      adhering ability. Moreover, overexpression of CTD903 in DLD1 and HCT116 reversed
      these phenotypes. Furthermore, downregulation of CTD903 enhanced Wnt/beta-catenin
      activation and subsequently increased transcription factors (Twist and Snail)
      expression, along with increased mesenchymal marker Vimentin and decreased
      epithelial marker ZO-1 level, while overexpressed CTD903 confirmed these
      associations. In conclusion, this study shows that LncRNA-CTD903 acts as a tumor
      suppressor in CRC and can inhibit cell invasion and migration through repressing
      Wnt/beta-catenin signaling, which plays important roles in EMT and CRC
      metastasis. 

PMID- 27035093
TI  - Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection
      against myocardial ischemia/reperfusion injury.
AB  - In the present study, we investigated the role of activating transcription factor
      6 (ATF6) in the mechanism by which chronic intermittent hypoxia (CIH) increases
      tolerance to myocardial ischemia/reperfusion (I/R). Experiments were conducted
      using a rat model of I/R injury in vivo and isolated Langendorff-perfused rat
      hearts ex vivo. The role of Akt in this process was also investigated in vitro
      using rat myoblast H9c2 cells. Cell viability was measured using a cell counting
      kit-8 assay. Lactate dehydrogenase (LDH) and creatine kinase cardiac isoenzyme
      activity were also measured as markers of cellular damage. ATF6, Akt and
      phosphorylated (p)-Akt expression was analyzed by western blot analysis. RNA
      interference (RNAi) was used to suppress ATF6 expression. We noted that ATF6
      expression in the ventricular myocardium was significantly increased in rats
      exposed to CIH. Furthermore, we noted that CIH preserved cardiac function after
      I/R in vivo and improved post-ischemic recovery of myocardial performance in
      isolated rat hearts. ATF6 and p-Akt expression was upregulated in cultured H9c2
      cells exposed to chronic mild hypoxia compared with those cultured under normoxic
      conditions. Chronic mild hypoxia attenuated subsequent simulated I/R injury in
      H9c2 cells (48 h), as evidenced by increased cell viability and decreased LDH
      activity. By contrast, decreased cell viability and increased LDH activity were
      observed in siRNA-ATF6-transfected H9c2 cells, with a concomitant reduction in p
      Akt levels. These results indicated that ATF6 upregulation is involved in the
      mechanism by which CIH attenuates myocardial I/R injury, possibly through
      upregulation of p-Akt, which is a key regulator of cardiomyocyte survival.

PMID- 27035094
TI  - Antiproliferative effects on colon adenocarcinoma cells induced by co
      administration of vitamin K1 and Lactobacillus rhamnosus GG.
AB  - Vitamin K (VK), an essential nutrient associated with the clotting cascade, has
      also been demonstrated to have anticancer properties in various cancer cells
      including colon cancer cells. Also probiotics have gained interest as potential
      anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown
      to inhibit cell proliferation and polyamine biosynthesis as well as to induce
      apoptosis in different human gastrointestinal cancer cells. Nevertheless, the
      exact mechanisms involved in these actions are not completely elucidated.
      Therefore, the aims of the present study were to evaluate in three differently
      graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of
      increasing VK1 concentrations, administered alone or in combination with viable
      L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by
      Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle
      evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72 h,
      caused inhibition of proliferation, induction of apoptosis and the cell cycle
      arrest in all the tested colon cancer cells. When VK1 and L.GG were co
      administered, the addition of increasing VK1 concentrations potentiated the
      probiotic antiproliferative effect in a dose-dependent manner, being also related
      to the individual features of each cell line. The effect was more evident in Caco
      2 and HT-29 cells compared to the less differentiated SW480. The enhanced
      antiproliferative efficacy due to co-administration of L.GG and VK1 could
      represent a suitable option in a functional food strategy for cancer growth
      inhibition and chemoprevention. 

PMID- 27035095
TI  - CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity.
AB  - Although squamous cell carcinomas (SqCCs) of the lungs, head and neck,
      oesophagus, and cervix account for up to 30% of cancer deaths, the mechanisms
      that regulate disease progression remain incompletely understood. Here, we use
      gene transduction and human tumor xenograft assays to establish that the tumour
      suppressor Cell adhesion molecule 1 (CADM1) inhibits SqCC proliferation and
      invasion, processes fundamental to disease progression. We determine that the
      extracellular domain of CADM1 mediates these effects by forming a complex with
      HER2 and integrin alpha6beta4 at the cell surface that disrupts downstream STAT3
      activity. We subsequently show that treating CADM1 null tumours with the JAK/STAT
      inhibitor ruxolitinib mimics CADM1 gene restoration in preventing SqCC growth and
      metastases. Overall, this study identifies a novel mechanism by which CADM1
      prevents SqCC progression and suggests that screening tumours for loss of CADM1
      expression will help identify those patients most likely to benefit from JAK/STAT
      targeted chemotherapies.

PMID- 27035096
TI  - Chemosensitizing effect of podophyllotoxin acetate on topoisomerase inhibitors
      leads to synergistic enhancement of lung cancer cell apoptosis.
AB  - Podophyllotoxin acetate (PA) acts as a radiosensitizer against non-small cell
      lung cancer (NSCLC) in vitro and in vivo. In this study, we examined its
      potential role as a chemosensitizer in conjunction with the topoisomerase
      inhibitors etoposide (Eto) and camptothecin (Cpt). The effects of combinations of
      PA and Eto/Cpt were examined with CompuSyn software in two NSCLC cell lines, A549
      and NCI-H1299. Combination index (CI) values indicated synergistic effects of PA
      and the topoisomerase inhibitors. The intracellular mechanism underlying
      synergism was further determined using propidium iodide uptake, immunoblotting
      and electrophoretic mobility shift assay (EMSA). Combination of PA with Eto/Cpt
      promoted disruption of the dynamics of actin filaments, leading to subsequent
      enhancement of apoptotic cell death via induction of caspase-3, -8, and -9,
      accompanied by increased phosphorylation of p38. Conversely, suppression of p38
      phosphorylation blocked the apoptotic effect of the drug combinations. Notably,
      CREB-1, a transcription factor, was constitutively activated in both cell types,
      and synergistically inhibited upon combination treatment. Our results
      collectively indicate that PA functions as a chemosensitizer by enhancing
      apoptosis through activation of the p38/caspase axis and suppression of CREB-1. 

PMID- 27035097
TI  - DNA damaging, cell cytotoxicity and serum albumin binding efficacy of the rutin
      Cu(ii) complex.
AB  - Flavonoids are widely used as anti-oxidants, anti-cancer agents and possess metal
      ion chelation properties. In this report we have investigated the DNA binding
      (and damaging), cell cytotoxicity and serum albumin (SA) binding efficacy of the
      rutin-Cu(ii) complex using differential spectroscopic methods. The rutin-Cu(ii)
      complex was able to intercalate into calf thymus DNA (ct-DNA) at lower
      concentrations and its DNA damaging properties were also confirmed from the
      agarose gel based assay, fluorescence and UV-vis studies. The copper complex was
      found to be effective against the growth of HeLa cells in vivo. The binding
      constants (Kb) of the rutin-Cu(ii) complex towards HSA and BSA were found to be
      (0.98 +/- 0.03) and (1.05 +/- 0.02) * 10(5) M(-1), respectively, at 299 K and
      observed to increase with the increase in temperature. Site selectivity studies
      revealed that the rutin-Cu(ii) complex binds near site 1 (subdomain IIA) of SAs.
      Thermodynamic parameters indicated that the mode of interaction of rutin and its
      copper complex with SAs are different from each other. Both DeltaH degrees  and
      DeltaS degrees  were observed to be positive for the interaction of the rutin
      Cu(ii) complex with SAs, indicating the presence of hydrophobic association in
      binding. The values of DeltaH degrees  were estimated to be negative (-42.07 +/-
      2.92 and -23.29 +/- 2.33 kJ mol(-1) for HSA and BSA respectively) in the binding
      of rutin with SAs. It implies that after chelation with Cu(ii) ion, rutin alters
      its binding mode which could have varying applications to its other
      physicochemical activities.

PMID- 27035098
TI  - MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in
      osteosarcoma.
AB  - The present study was conducted to investigate the expression of miR-603 in
      osteosarcoma cells, and the effect of miR-603 on the biological behavior and
      expression of breast cancer cell 2 (BRCC2) in osteosarcoma cells. In the present
      study, qRT-PCR was used to measure the levels of miRNA and mRNA. The results
      showed that miR-603 was significantly upregulated in human osteosarcoma tissues
      and cell lines. MTT and colony formation assays were employed to evaluate the
      role of miR-603 in the regulation of osteosarcoma cell proliferation. The results
      showed that overexpression of miR-603 promoted the proliferation of MG-63 and
      U2OS cells. Furthermore, a nude mouse subcutaneous tumor model indicated that miR
      603 promoted osteosarcoma growth in vivo. Moreover, miR-603 expression levels
      were increased in patients with distant metastasis in comparison with levels in
      patients without distant metastasis. We discovered that BRCC2 may be a target of
      miR-603. Our results demonstrated that overexpression of miR-603 suppressed BRCC2
      protein expression, and an miR-603 inhibitor enhanced BRCC2 protein expression as
      determined by western blot assay and immunohistochemical analysis. Luciferase
      reporter assays confirmed that BRCC2 is a direct target of miR-603 in
      osteosarcoma cells, and the results suggest that miR-603 downregulates BRCC2
      expression in osteosarcoma via translational inhibition. Finally, we found that
      the reduction in BRCC2 expression induced by miR-603 was responsible for the
      enhanced colony formation and proliferative ability noted in the MG-63 and U2OS
      cells. In conclusion, miR-603 enhanced osteosarcoma growth by downregulation of
      BRCC2 expression via translational inhibition. 

PMID- 27035099
TI  - X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism:
      Identification and in vitro study of a novel small indel in the NR0B1 gene.
AB  - DAX1 is an orphan nuclear receptor that has a key role in the development and
      function of the adrenal and reproductive axes. Mutations in NR0B1, the gene
      encoding DAX1, result in X-linked adrenal hypoplasia congenita (AHC) and
      hypogonadotropic hypogonadism (HHG). A Chinese pedigree with X-linked AHC and HHG
      was investigated in the present study. Sequence analysis identified a novel small
      indel variant, c.195_207delinsTG, in the NR0B1 gene. To determine the effect of
      this variant on DAX1 expression, reverse-transcription quantitative PCR and
      western blot assays were performed. The mRNA expression levels in carriers of
      mutant NR0B1 were significantly reduced (62% decrease) compared to those in
      individuals with wild-type NR0B1 (WT). The c.195_207delinsTG mutation was
      demonstrated to lead to various truncated DAX1 proteins, including the C-terminal
      truncated DAX1, which was only detected in the cytoplasm, and the N-terminal
      truncated DAX1, which was present in the cytoplasm and nucleus. A luciferase
      assay was then performed to assess the repressor function of DAX1 in modulating
      steroidogenic factor 1 (SF-1)-mediated transactivation. WT DAX1 significantly
      suppressed the SF-1-mediated promoter activity of the steroidogenic acute
      regulatory protein by 35.5+/-1.9%. In contrast to other known pathogenic
      mutations which abolish the repressor function of DAX1, the c.195_207delinsTG
      mutant proxkduced a higher repressor activity, demonstrating a 49.9+/-2.6%
      reduction of promoter activity. These findings suggested that the mutation of
      NR0B1 in X-linked AHC with HHG enhanced the function of DAX1 to repress SF-1
      activation, while DAX1 is expected to have additional roles in the pathological
      mechanism. 

PMID- 27035100
TI  - GGsTOP increases migration of human periodontal ligament cells in vitro via
      reactive oxygen species pathway.
AB  - GGsTOP is a novel and selective inhibitor of gamma-glutamyl transferase (GGT), a
      cell-surface enzyme that has a key role in glutathione homeostasis and the
      maintenance of cellular reactive oxygen species (ROS). ROS are essential for
      wound healing. However, little is known about the molecular mechanisms underlying
      the inhibition of GGT by GGsTOP in human periodontal ligament cells (hPLCs). The
      present study assessed GGT expression in mouse periodontal ligament tissues, GGT
      activity in hPLCs, and the potential physiological effect of GGsTOP on hPLC
      migration. Immunohistochemical analysis confirmed that GGT was widely expressed
      in mouse periodontal ligament tissue. Treatment with GGsTOP was associated with
      greater proliferation and migration of hPLCs, and higher levels of cellular ROS
      compared with untreated hPLCs. However, the increase in intracellular ROS was
      attenuated in hPLCs co-cultured with the anti-oxidant N-acetylcysteine (NAC), a
      precursor of glutathione. The higher ROS levels associated with GGsTOP treatment
      were in parallel with increases in the levels of type I collagen and alpha smooth
      muscle actin, which was inhibited in hPLCs co-cultured with NAC. Thus, GGsTOP may
      promote hPLC migration and participate in the maintenance of the periodontal
      ligament apparatus via the ROS pathway. 

PMID- 27035101
TI  - Quantitative morphological characterization of bicontinuous Pickering emulsions
      via interfacial curvatures.
AB  - Bicontinuous Pickering emulsions (bijels) are a physically interesting class of
      soft materials with many potential applications including catalysis,
      microfluidics and tissue engineering. They are created by arresting the spinodal
      decomposition of a partially-miscible liquid with a (jammed) layer of interfacial
      colloids. Porosity L (average interfacial separation) of the bijel is controlled
      by varying the radius (r) and volume fraction (phi) of the colloids (L?r/phi).
      However, to optimize the bijel structure with respect to other parameters, e.g.
      quench rate, characterizing by L alone is insufficient. Hence, we have used
      confocal microscopy and X-ray CT to characterize a range of bijels in terms of
      local and area-averaged interfacial curvatures; we further demonstrate that
      bijels are bicontinuous using an image-analysis technique known as 'region
      growing'. In addition, the curvatures of bijels have been monitored as a function
      of time, which has revealed an intriguing evolution up to 60 minutes after bijel
      formation, contrary to previous understanding.

PMID- 27035102
TI  - Work-Family Conflict and Employee Well-Being Over Time: The Loss Spiral Effect.
AB  - OBJECTIVE: The development of work-family conflict over time was analyzed using
      Conservation of Resources Theory. METHOD: The reciprocal effect between work
      family conflict and employee well-being was tested with cross-lagged analyses on
      the basis of three waves. The sample comprised 713 employees of a Portuguese
      service organization. RESULTS: Structural equation modeling analyses, with sex,
      age, and parental demand controlled, indicated that the work-family conflict at
      T1 and T2 decreases the employee psychological well-being at T2 and T3,
      respectively. Furthermore, employee psychological well-being at T2 had a
      longitudinal cross-lagged effect on work-family at T3. We concluded that employee
      psychological well-being at T2 predicted work-family at T3, which was a
      subsequent outcome of work-family conflict on T1. CONCLUSIONS: This paper
      highlighted the importance of organizations to consider work-family conflict to
      ensure employees' well-being because they develop reciprocal relationship with a
      loss spiral effect.

PMID- 27035103
TI  - Implementing a Sleep Health Education and Sleep Disorders Screening Program in
      Fire Departments: A Comparison of Methodology.
AB  - OBJECTIVE: The objective of this study is to compare three methods of
      administering a sleep health program (SHP) in fire departments. METHODS: An SHP,
      comprising sleep health education and screening for common sleep disorders, was
      implemented in eight fire departments using three approaches: expert-led, train
      the-trainer, and online. Participation rates, knowledge assessments, surveys, and
      focus group interviews were analyzed to assess the reach and effectiveness of the
      methodologies. RESULTS: The Expert-led SHP had the highest participation rate,
      greatest improvement in knowledge scores, and prompted more firefighters to seek
      clinical sleep disorder evaluations (41%) than the other approaches (20 to 25%).
      Forty-two percent of focus group participants reported changing their sleep
      behaviors. CONCLUSION: All approaches yielded reasonable participation rates, but
      expert-led programs had the greatest reach and effectiveness in educating and
      screening firefighters for sleep disorders.

PMID- 27035104
TI  - A 7-Step Strategy for the Implementation of Worksite Lifestyle Interventions:
      Helpful or Not?
AB  - OBJECTIVE: The aim of this study was to evaluate the use of and adherence to a 7
      step strategy for the development, implementation, and continuation of a
      comprehensive, multicomponent lifestyle program. METHODS: Strategy use and
      adherence was assessed with 12 performance indicators. Data were collected by
      combining onsite monitoring with semi-structured interviews at baseline and
      follow-up (6, 12, and 18 months). RESULTS: Not all performance indicators were
      met so partial strategy adherence was obtained. The strategy could be improved on
      the following aspects: support among management, project structure, adaptation to
      needs of employees, planning, and maintenance. CONCLUSION: The results of this
      evaluation indicate that strategy adherence facilitated structured development
      and implementation. On the basis of the qualitative data, this study suggests
      that when improvements will be made on both the content and performance, the 7
      step strategy could be an effective tool to successfully implement a
      multicomponent WHPP.

PMID- 27035105
TI  - Congruence of Organizational Self-Score and Audit-Based Organizational
      Assessments of Workplace Health Capabilities: An Analysis of the HealthLead
      Workplace Accreditation.
AB  - OBJECTIVE: The aim of this study was to provide descriptive characteristics of
      companies accredited as part of the HealthLead Workplace Accreditation and to
      assess congruence between data reported via online organizational self-assessment
      and third-party onsite audit. METHODS: Synthesized organizational level data
      collected through the HealthLead accreditation process (N = 22). Online self
      assessment and onsite third-party audit data were compared using paired t-tests.
      RESULTS: Statistical tests revealed significantly higher onsite audit scores than
      organizational self-assessment scores. Descriptive analyses demonstrated that
      Outcomes Reporting was the lowest scoring area among all companies. Companies
      also varied widely in levels of Leadership Support for wellness. CONCLUSIONS:
      Gaps observed between organizational self-assessment and onsite audit scores were
      relatively stable across the sample, indicating that observed differences may be
      process related. Organizations awarded accreditation show a wide variation in
      Leadership Support, and Outcomes Reporting appears to be low across the sample.

PMID- 27035106
TI  - Inflammatory Markers and Genetic Polymorphisms in Workers Exposed to Flour Dust.
AB  - OBJECTIVE: The aim of this study is to evaluate inflammatory markers and pro
      inflammatory CD14 and Toll-like Receptor 4 (TLR4) polymorphisms in workers
      exposed to flour dust. METHODS: Polymorphisms in TLR4 and CD14 were identified in
      our study population of 167 workers that included 63 healthy subjects (HS), 45
      atopic subjects (A), and 59 subjects diagnosed clinically with occupational
      asthma/rhinitis (OAR). Endpoint measures in this study included fractional
      exhaled nitric oxide and serum concentrations of interleukin IL-6, IL-8, and
      tumor necrosis factor-alpha (TNF-alpha). RESULTS: We identified a polymorphism in
      CD14 (rs2569190) that may be differentially expressed (P = 0.06). IL-6
      concentrations in the serum were significantly higher in the A and OAR groups (P
      < 0.01) than in subjects in the HS group, while IL-8 concentrations were
      significantly elevated only in the OAR group (P < 0.01). Interestingly, TNF-alpha
      concentrations in the OAR group were significantly reduced when compared with
      subjects in the HS group (P < 0.01). CONCLUSION: Cytokines are likely a defensive
      response in atopic and healthy workers. A protective genotype is hypothesized for
      occupational asthma.

PMID- 27035107
TI  - Occupational Injury Surveillance Among Law Enforcement Officers Using Workers'
      Compensation Data, Illinois 1980 to 2008.
AB  - OBJECTIVE: Injuries among law enforcement officers are common, but poorly
      understood; workers' compensation (WC) data are an underutilized tool for
      occupational surveillance. METHODS: A stratified analysis of WC claims among four
      categories of law enforcement officers used descriptive techniques, linear and
      robust regression. RESULTS: Eighteen thousand eight hundred ninety-two officers
      filed claims from 1980 to 2008. Correctional officers had the highest rates, with
      leading causes of falls and assaults; motor vehicle crashes were the most common
      cause of injury among state police. Total monetary compensation was lower for
      correctional officers, but was explained by lower time lost and lower average
      weekly wage. CONCLUSION: The rate and types of injuries varied by subgroups, with
      correctional officers having the majority of injuries, but lower severity. WC
      data elucidate causes and outcomes of occupational injuries, which can guide
      prevention.

PMID- 27035108
TI  - The Economic Impact of Psychological Distress in the Australian Coal Mining
      Industry.
AB  - OBJECTIVE: The aim of this study was to estimate the economic impact of
      psychological distress among employees of the Australian Coal Mining Industry.
      METHODS: Sample data were gathered from 1456 coal mining staff across eight sites
      in two Australian states. Two measures were taken of work time lost over four
      weeks due to psychological distress: (1) full-day absences; (2) presenteeism.
      Lost work time was valued using hourly wages. Sample data was modeled to estimate
      annual monetary losses for the Australian Coal Mining Industry. RESULTS: For the
      sample, estimated annual value of time lost due to psychological distress was
      $4.9 million ($AUS2015) ($0.61 million per mine), and for the Australian Coal
      Mining Industry, $153.8 million ($AUS2015). CONCLUSION: Psychological distress is
      a significant cost for the Australian Coal Mining Industry. Relevant intervention
      programs are potentially cost-effective.

PMID- 27035109
TI  - Mild oxidative stress induced by a low dose of cisplatin contributes to the
      escape of TRAIL-mediated apoptosis in the ovarian cancer SKOV3 cell line.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is
      expressed in ovarian tissue and is widely thought to exhibit strong antitumor
      activity in a variety of tumor cell types. Therefore, we hypothesized that the
      cisplatin resistance of ovarian cancer is linked to the ability to escape from
      TRAIL-mediated apoptosis. We demonstrated that cisplatin-resistant ovarian cancer
      cell line SKOV3/DDP tolerated treatment with TRAIL, in contrast to the cisplatin
      sensitive ovarian cancer cell line SKOV3. SKOV3/DDP cells exhibited a much higher
      cell viability and a lower apoptosis rate than SKOV3 cells after treatment with
      TRAIL. To determine whether cisplatin induced the tolerance of TRAIL, we
      pretreated the SKOV3 cells with cisplatin in the presence of TRAIL. This revealed
      that a low dose of cisplatin (1 uM) increased the TRAIL tolerance of SKOV3 cells.
      Furthermore, cisplatin induced oxidative stress in both the SKOV3/DDP and SKOV3
      cells, although the oxidative stress level of the SKOV3/DDP cells was generally
      much higher than that noted in the SKOV3 cells. Similarly, a low dose of hydrogen
      peroxide increased the TRAIL tolerance in SKOV3 cells. Notably, the TRAIL
      tolerance in the SKOV3 and SKOV3/DDP cells could be abrogated by the oxidative
      stress scavenger N-acetyl-cysteine. These results suggest that a low dose of
      cisplatin induces the tolerance of TRAIL in SKOV3 cells at least partly,
      depending on the oxidative stress signaling pathway. 

PMID- 27035110
TI  - MicroRNA-29b inhibits TGF-beta1-induced fibrosis via regulation of the TGF
      beta1/Smad pathway in primary human endometrial stromal cells.
AB  - Transforming growth factor (TGF)-beta1 has a key role in the regulation of
      fibrosis and organ dysfunction. During the pathogenesis and progression of vital
      organ fibrosis, the microRNA (miR)-29 family is irregularly downregulated and
      exogenous supplementation of miR-29b has a strong anti-fibrotic capacity.
      However, whether TGF-beta1 is able to provoke endometrial fibrosis, and the role
      of miR-29 in endometrial fibrosis remain unclear. In the present study, RT-qPCR,
      immunocytochemistry, western blot analysis, scanning electron microscopy,
      immunofluorescence staining, cell proliferation assay and flow cytometric
      analysis were employed. The results demonstrated that the expression levels of
      collagen, type 1, alpha 1 (COL1A1), alpha-smooth muscle actin (alpha-SMA) and
      phosphorylated (p)-Smad2/3 were increased, whereas miR-29b and maternally
      expressed gene 3 (MEG3) were decreased in primary endometrial stromal cells
      (ESCs) in response to TGF-beta1 stimulation, in a time and dose-dependent manner.
      Furthermore, overexpression of miR-29b markedly reduced the expression levels of
      COL1A1 and alpha-SMA, and decreased the expression and nuclear accumulation of p
      Smad2/3. In addition, ectopic overexpression of miR-29b increased the expression
      levels of MEG3, inhibited myofibroblast-like cell proliferation and induced
      apoptosis. These findings indicated that miR-29b may have a significant anti
      fibrotic role, and may attenuate TGF-beta1-induced fibrosis in ESCs. Therefore,
      exogenous miR-29b may serve as a potential therapeutic agent for the treatment of
      endometrial fibrosis. 

PMID- 27035111
TI  - Vitamin E confers cytoprotective effects on cardiomyocytes under conditions of
      heat stress by increasing the expression of metallothionein.
AB  - Heat stress (HS) is commonly used to refer to the heat load that an individual is
      subjected to due to either metabolic heat, or environmental factors, including
      high temperatures and high humidity levels. HS has been reported to affect and
      even damage the functioning of various organs; overexposure to high temperatures
      and high humidity may lead to accidental deaths. It has been suggested that the
      cardiovascular system is primarily targeted by exposure to HS conditions; the HS
      induced dysfunction of cardiomyocytes, which is characterized by mitochondrial
      dysfunction, may result in the development of cardiovascular diseases. The
      excessive production of reactive oxygen species (ROS) also participates in
      mitochondrial dysfunction. However, effective methods for the prevention and
      treatment of mitochondrial and cardiovascular dysfunction induced by exposure to
      HS are lacking. In the present study, we hypothesized that vitamin E (VE), an
      antioxidant, is capable of preventing oxidative stress and mitochondrial injury
      in cardiomyocytes induced by exposure to HS. The results revealed that pre
      treatment with VE increased the expression of metallothionein (MT), which has
      previously been reported to confer cytoprotective effects, particularly on the
      cardiovascular system. Pre-treatment with VE restored mitochondrial function in
      cardiomyocytes under conditions of HS by increasing the expression of peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), nuclear
      respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), and
      by increasing adenosine triphosphate (ATP) levels. Furthermore, pre-treatment
      with VE decreased the production of ROS, which was induced by exposure to HS and
      thus exerted antioxidant effects. In addition, pre-treatment with VE attenuated
      oxidative stress induced by exposure to HS, as demonstrated by the increased
      levels of antioxidant enzymes [superoxide dismutase (SOD) and glutathione (GSH)],
      and by the decreased levels of markers of oxidative injury [malondialdehyde (MDA)
      and lactate dehydrogenase (LDH)]. Taken together, these findings suggest that pre
      treatment with VE can prevent mitochondrial dysfunction and oxidative stress in
      cardiomyocytes induced by exposure to HS, by increasing the expression of MT.

PMID- 27035112
TI  - Cholesterol metabolism in cardiac sarcoidosis.
AB  - BACKGROUND AND AIMS: Patients with cardiac sarcoidosis (CS) suffer from
      myocardial inflammation, but atherosclerosis is not infrequent in these patients.
      However, the classical atherosclerotic risk factors, such as perturbed serum
      lipids and whole-body cholesterol metabolism, remain unravelled in CS. METHODS:
      We assessed serum non-cholesterol sterols, biomarkers of whole-body cholesterol
      synthesis and cholesterol absorption efficiency, with gas-liquid chromatography
      in 39 patients with histologically verified CS and in an age-adjusted random
      population sample (n = 124). RESULTS: CS was inactive or responding to treatment
      in all patients. Concentrations of serum, LDL, and HDL cholesterol and serum
      triglycerides were similar in CS patients and in control subjects. Cholesterol
      absorption markers were higher in CS patients than in controls (eg serum
      campesterol to cholesterol ratio in CS 246 +/- 18 vs in controls 190 +/- 8 10(2)
      x MUmol/mmol of cholesterol, p = 0.001). Cholesterol synthesis markers were lower
      in CS patients than in controls (eg serum lathosterol to cholesterol ratio in CS
      102 +/- 8 vs in controls 195 +/- 5 10(2) x MUmol/mmol of cholesterol, p = 0.000).
      In CS patients, cholesterol absorption markers significantly correlated with
      plasma prohormone brain natriuretic peptide (proBNP), a marker of hemodynamic
      load. CONCLUSION: High cholesterol absorption efficiency, which is suggested to
      be atherogenic, characterized the metabolic profile of cholesterol in CS
      patients. The association between cholesterol absorption efficiency and plasma
      proBNP concentration, which suggests a link between inflammation, cholesterol
      homeostasis, and hemodynamic load, warrants further studies in order to confirm
      this finding and to reveal the underlying mechanisms.

PMID- 27035113
TI  - Cholesterol-lowering interventions and stroke: Insights from IMPROVE-IT.
AB  - The relationship of cholesterol with stroke is much less clear than its
      relationship with myocardial infarction, thus confounding the interpretation of
      results with cholesterol-lowering trials. Because for long time the only lipid
      lowering intervention reducing stroke was statins, it has been actually argued
      that reduction in stroke found in statin trials is not due to statins' ability to
      reduce LDL cholesterol, but to other "pleiotropic" effects, unrelated to
      cholesterol lowering. In re-analyzing the relationship of cholesterol lowering
      versus changes in the risk of stroke in a meta-regression of all cholesterol
      lowering interventions, including also non-statin interventions, we had
      previously reached the opposite conclusion: that some reduction in stroke has to
      be expected proportional to cholesterol reduction. We had predicted that a 1%
      reduction of total cholesterol-no matter by what intervention produced-was
      associated with a 0.8% relative risk reduction of stroke. Data from the recently
      published Improved Reduction of Outcomes: Vytorin Efficacy International Trial
      (IMPROVE-IT) now offer a clear proof of this concept, demonstrating that pure
      cholesterol lowering, as obtained with ezetimibe, plays an important role in
      reducing stroke. IMPROVE-IT data, showing a 13.3% reduction in total cholesterol
      at one year in association with a hazard ratio (HR) of 0.86 for total stroke
      during the trial, are very closely aligned with the relative risk of 0.90
      predicted on the basis of the totality of lipid lowering interventions. These
      data are important to predict stroke outcomes in currently ongoing trials now
      testing PCSK9 or cholesterol ester transfer protein inhibitors. 

PMID- 27035114
TI  - Trends in the proportions of stroke subtypes and coronary heart disease in the
      Japanese men and women from 1995 to 2009.
AB  - BACKGROUND: The limited evidence on trends in the proportions of stroke subtypes
      and coronary heart disease in Japan. METHODS AND RESULTS: Stroke and coronary
      heart disease registrations from three periods including 1995 to 1999, 2000 to
      2004, and 2005 to 2009 were examined for residents aged 55-74 years for each
      period who were admitted with acute cardiovascular disease. Subjects who
      experienced an onset of stroke, or coronary heart disease, or moved at the
      beginning of each period were excluded. There were 3181 cases of strokes and 768
      cases of coronary heart disease in 1995-2009. The age-adjusted proportion of
      intraparenchymal hemorrhage was 34%, 25%, and 24% (p = 0.02) for men, and 27%,
      29%, and 30% (p = 0.41) for women; ischemic stroke was 57%, 68%, and 73% (p =
      0.002) for men, and 46%, 52%, and 58% (p = 0.02) for women; and embolic
      infarction was 23%, 31%, and 32% (p < 0.001) for men, and 21%, 23%, and 30% (p =
      0.009) for women, respectively. The proportions of sudden cardiac death and
      myocardial infarction among total coronary heart disease did not change during
      the three periods for either sex. CONCLUSIONS: Between 1995-1999 and 2005-2009,
      the proportion of intraparenchymal hemorrhage among all types of stroke decreased
      for men, while the proportions of ischemic stroke among all types of stroke and
      embolic infarction among ischemic stroke increased for both men and women.

PMID- 27035115
TI  - Tumor-promoting function of single nucleotide polymorphism rs1836724 (C3388T)
      alters multiple potential legitimate microRNA binding sites at the 3'
      untranslated region of ErbB4 in breast cancer.
AB  - ErbB4 can act as either a tumor-suppressor gene or an oncogene in breast cancer.
      Multiple genetic factors including single nucleotide polymorphisms (SNPs) affect
      gene expression patterns. Multiple 3'-untranslated region (3'-UTR) SNPs reside
      within the target binding site of microRNAs, which can strengthen or weaken
      binding to target genes. The present study aimed to predict potential 3'-UTR
      variants of ErbB4 that alter the target binding site of microRNAs (miRNAs) and to
      clarify the association of the potential variant with the risk of developing
      breast cancer. In silico prediction was performed to identify potential
      functional SNPs within miRNA target binding sites in the 3'-UTR of ErbB4. Thus,
      146 patients and controls were genotyped using restriction fragment length
      polymorphism-polymerase chain reaction. In addition to the Cochran-Armitage test
      for trend, allele and genotype frequency differences were determined to
      investigate the association between rs1836724 and the susceptibility to breast
      cancer. Bioinformatics analysis identified rs1836724 to be a polymorphism in the
      seed region of four miRNA binding sites (hsa-miR335-5p, hsa-miR-28-5p, has-miR
      708-5p and has-miR-665), which may participate in the development of breast
      cancer. Logistic regression data indicated that the T allele of the polymorphism
      [OR (95% CI)=1.72 (1.056-2.808), P=0.029] is associated with the risk of breast
      cancer. Using bioinformatics tools, a correlation was indicated between the
      presence of the T allele and a reduction in ErbB4 RNA silencing based on miRNA
      interaction. Furthermore, case subgroup data analysis revealed an association
      between the C/T genotype and an ER positive phenotype [OR (95% CI)=6.00 (1.082
      33.274), P=0.028] compared with the T/T genotype. ErbB4 and estrogen receptor 1
      (ESR1) are regulated by identical miRNAs thus there may be a competition for
      binding sites. Due to this pattern, if the interaction between miRNAs with one
      gene is reduced, it may be consistent with the increase in interaction with
      another one. Therefore, more interaction with rs1836724 C variant within ErbB4
      may be associated with higher expression of ESR1 (ER-positive phenotype). miRNAs
      interact with ErbB4 mRNA more frequently when it carries C allele at the
      rs1836724 position compared with the T carriers. Therefore, the identical miRNA
      interacts with ESR1 less frequently when ErbB4 mRNA has a C allele. Therefore,
      ESR1 expression may be higher when ErbB4 mRNA has a C allele. 

PMID- 27035116
TI  - Knockdown of ANXA1 suppresses the biological behavior of human NSCLC cells in
      vitro.
AB  - Annexin A1 (ANXA1) is a member of the annexin superfamily. Previous studies have
      reported that ANXA1 is highly expressed in various types of malignant tumor;
      however, its role in the progression of non-small cell lung cancer (NSCLC)
      remains to be fully clarified. The present study aimed to investigate the
      oncogenic role of ANXA1 in NSCLC cells in vitro. RNA interference was used to
      downregulate ANXA1 expression in A549 and H1299 cells using a small interfering
      RNA lentiviral vector. Subsequently, cell proliferation and migration were
      detected using Cell Counting kit-8, clone formation, wound healing and Transwell
      chamber assays. Successful transfection was confirmed using fluorescence
      microscopy, which demonstrated that ANXA1 had been efficiently inhibited. ANXA1
      knockdown suppressed the proliferation, migration and invasion of NSCLC cells. In
      conclusion, the present study provided evidence suggesting that ANXA1 may
      contribute to the growth and invasion of NSCLC cell lines, and ANXA1 may be
      exploited as an in vitro therapeutic target for the treatment of NSCLC. 

PMID- 27035117
TI  - Expression profile analysis of head and neck squamous cell carcinomas using data
      from The Cancer Genome Atlas.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the major histological type of
      head and neck cancer and no curative treatments are currently available. Using
      advanced sequencing technologies, The Cancer Genome Atlas (TCGA) has produced
      large-scale sequencing data, which provide unprecedented opportunities to reveal
      molecular mechanisms of cancer. The present study analyzed the mRNA and micro
      (mi)RNA expression data of HNSCC and normal control tissues released by the TCGA
      database using a bioinformatics approach to explore underlying molecular
      mechanisms. The mRNA and miRNA expression data were downloaded from the TCGA
      database and differentially expressed genes (DEGs) and miRNAs (DEMs) between
      HNSCC and normal head and neck tissues were identified using TwoClassDif.
      Subsequently, the gene functions and pathways which are significantly altered in
      HNSCC were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathway enrichment analysis. Regulatory networks among DEGs
      and DEMs were then constructed, and transcription factors (TFs) potentially
      regulating the DEGs and DEMs were determined and a TF - miRNA - gene network was
      established. A total of 2,594 significant DEGs (1,087 upregulated and 1,507
      downregulated), and 25 DEMs (8 upregulated and 17 downregulated) were identified
      in HNSCC compared with normal control samples. These DEGs were significantly
      enriched in GOs and KEGG pathways such as mitosis, cell cycle, Wnt, JAK/STAT and
      TLR signaling pathway. CPBP, NF-AT1 and miR-1 were situated in the central hub of
      the TF - miRNA - gene network, underlining their central roles in regulatory
      processes specific for HNSCC. The present study enhanced the current
      understanding of the molecular mechanisms underlying HNSCC and may offer novel
      strategies for its prevention, diagnosis and treatment. 

PMID- 27035118
TI  - Whole-genome re-sequencing for the identification of high contribution
      susceptibility gene variants in patients with type 2 diabetes.
AB  - There is increasing evidence that several genes are associated with an increased
      risk of type 2 diabetes (T2D); genome-wide association investigations and whole
      genome re-sequencing investigations offer a useful approach for the
      identification of genes involved in common human diseases. To further investigate
      which polymorphisms confer susceptibility to T2D, the present study screened for
      high-contribution susceptibility gene variants Chinese patients with T2D using
      whole-genome re-sequencing with DNA pooling. In total, 100 Chinese individuals
      with T2D and 100 healthy Chinese individuals were analyzed using whole-genome re
      sequencing using DNA pooling. To minimize the likelihood of systematic bias in
      sampling, paired-end libraries with an insert size of 500 bp were prepared for in
      T2D in all samples, which were then subjected to whole-genome sequencing. Each
      library contained four lanes. The average sequencing depth was 35.70. In the
      present study, 1.36 GB of clean sequence data were generated, and the resulting
      calculated T2D genome consensus sequence covered 99.88% of the hg19 sequence. A
      total of 3,974,307 single nucleotide polymorphisms were identified, of which
      99.88% were in the dbSNP database. The present study also found 642,189
      insertions and deletions, 5,590 structure variants (SVs), 4,713 copy number
      variants (CNVs) and 13,049 single nucleotide variants. A total of 1,884 somatic
      CNVs and 74 somatic SVs were significantly different between the cases and
      controls. Therefore, the present study provided validation of whole-genome re
      sequencing using the DNA pooling approach. It also generated a whole-genome re
      sequencing genotype database for future investigations of T2D. 

PMID- 27035119
TI  - Evaluation of genetic diversity among strains of the human gut commensal
      Bifidobacterium adolescentis.
AB  - Bifidobacteria are members of the human gut microbiota, being numerically
      dominant in the colon of infants, while also being prevalent in the large
      intestine of adults. In this study, we determined and analyzed the pan-genome of
      Bifidobacterium adolescentis, which is one of many bacteria found in the human
      adult gut microbiota. In silico analysis of the genome sequences of eighteen B.
      adolescentis strains isolated from various environments, such as human milk,
      human feces and bovine rumen, revealed a high level of genetic variability,
      resulting in an open pan-genome. Compared to other bifidobacterial taxa such as
      Bifidobacterium bifidum and Bifidobacterium breve, the more extensive B.
      adolescentis pan-genome supports the hypothesis that the genetic arsenal of this
      taxon expanded so as to become more adaptable to the variable and changing
      ecological niche of the gut. These increased genetic capabilities are
      particularly evident for genes required for dietary glycan-breakdown. 

PMID- 27035120
TI  - Tendon-derived progenitor cells improve healing of collagenase-induced flexor
      tendinitis.
AB  - Tendinitis is a common and a performance-limiting injury in athletes. This study
      describes the value of intralesional tendon-derived progenitor cell (TDPC)
      injections in equine flexor tendinitis. Collagenase-induced tendinitis was
      created in both front superficial digital flexor (SDF) tendons. Four weeks later,
      the forelimb tendon lesions were treated with 1 * 107 autogenous TDPCs or saline.
      Tendinitis was also induced by collagenase in one hind SDF tendon, to study the
      survival and distribution of DiI-labeled TDPCs 1, 2, 4, and 6 weeks after
      injection. The remaining normal tendon was used as a "control." Twelve weeks
      after forelimb TDPC injections, tendons were harvested for assessment of matrix
      gene expression, biochemical, biomechanical, and histological characteristics.
      DiI-labeled TDPCs were abundant 1 week after injection but gradually declined
      over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection,
      collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in
      both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and
      maximal stresses of the TDPC group were significantly greater (p = 0.005) than
      the saline group's and similar (p = 0.6) to normal tendon. However, the elastic
      modulus of the TDPC and saline groups were not significantly different (p =
      0.32). Histological assessment of the repair tissues with Fourier transform
      second harmonic generation imaging demonstrated that collagen alignment was
      significantly better (p = 0.02) in TDPC group than in the saline controls. In
      summary, treating collagenase-induced flexor tendon lesions with TDPCs improved
      the tensile strength and collagen fiber alignment of the repair tissue. Study
      Design (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res 34:2162-2171, 2016.

PMID- 27035121
TI  - Lazaroid U83836E protects the heart against ischemia reperfusion injury via
      inhibition of oxidative stress and activation of PKC.
AB  - Oxidative stress has been demonstrated to be important during myocardial
      ischemia/reperfusion injury (MIRI). The lazaroid U83836E, which combines the
      amino functionalities of the 21-aminosteroids with the antioxidant ring portion
      of vitamin E, is a reactive oxygen species scavenger. The aim of the current
      study was to investigate the effect of U83836E on MIRI and its mechanisms of
      action. Rat hearts were subjected to 30 min ligation of the left anterior
      descending coronary artery, followed by 2 h reperfusion. The results demonstrated
      that at 5 mg/kg, U83836E markedly protected cardiac function in
      ischemia/reperfusion rat models, decreased the malondialdehyde content and
      creatinine kinase activity, while increasing superoxide dismutase and glutathione
      peroxidase activity. Additionally, U83836E significantly decreased the
      histological damage to the myocardium, reduced the area of myocardial infarction
      in the left ventricle and modified the mitochondrial dysfunction. Furthermore,
      U83836E enhanced the translocation of protein kinase Cepsilon (PKCepsilon) from
      the cytoplasm to the membrane. However, the cardioprotective effects of U83836E
      were reduced in the presence of the PKC inhibitor, chelerythrine (1 mg/kg).
      Therefore, the results of the present study suggest that U83836E has a potent
      protective effect against MIRI in rat models through the direct anti-oxidative
      stress mechanisms and the activation of PKC signaling. 

PMID- 27035122
TI  - Receptor-interacting protein-1 promotes the growth and invasion in gastric
      cancer.
AB  - The receptor-interacting protein-1 (RIP-1) is an important molecular in
      inflammation signaling pathways, but the role of RIP-1 in gastric cancer is
      largely unknown. In this study, we tested the expression of RIP-1 in gastric
      cancer samples and analyzed the effects of expression of RIP-1 on the prognosis
      in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer
      cells and addressed the functional role of RIP-1 using a xenograft mouse model. A
      lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS
      cells. The effect of RIP-1 siRNA on HGC and AGS cells were investigated by cell
      proliferation assay and invasion assay. Furthermore, we examined the role of RIP
      1-siRNA on HGC cells in the mice with subcutaneous xenograft tumor, and
      preliminarily analyzed the underlying mechanisms. The results indicated that the
      expression of RIP-1 in the gastric cancer tissues was significantly higher than
      the expression in the normal gastric tissues. Additionally, RIP-1
      immunoreactivity was positive at the site of invasion, but little or no
      immunoreactivity was detected at the gastric cancer parts of interstitial
      substance. Gastric cancer patients with high expression of RIP-1 had a poor
      survival rate. RIP-1 expression in the gastric cancer cell lines were general.
      HGC-R-1-RNAi-LV inhibited HGC and AGS cell proliferation and invasion ability in
      vitro. RIP-NF-kappaB/AP-1-VEGF-C signaling pathways have a crucial role in the
      regulate the biological functions of HGC cells. HGC-R-1-RNAi-LV suppressed tumor
      growth in the HGC cell subcutaneous xenograft model. In conclusion, our data
      indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro
      and in vivo, additionally providing evidence that targeting RIP-1 may be useful
      in the treatment of gastric cancer. 

PMID- 27035123
TI  - The effect of hydrogen bonding propensity and enantiomeric composition on the
      dynamics of supercooled ketoprofen - dielectric, rheological and NMR studies.
AB  - The aim of this work is to analyze in detail the effect of small hydrogen bonding
      (HB) structures and enantiomeric composition on the dynamics of glass-forming
      liquid ketoprofen. For that purpose dielectric relaxation, rheological and NMR
      studies were performed. Investigated samples are racemic ketoprofen, a single
      enantiomer of ketoprofen and a racemic ketoprofen methyl ester with no tendency
      to form HB dimers. The combination of complementary experimental techniques
      enables us to show that macroscopic viscosity eta and alpha-relaxation time
      taualpha have nearly the same temperature dependencies, whereas the relation
      between the viscosity (or molecular reorientation) and the translational self
      diffusion coefficient violates Stokes-Einstein law already at high temperature.
      Additionally, based on dielectric relaxation studies performed on increased
      pressure we were able to identify similarities and key differences in the
      supercooled liquid dynamics of investigated materials affected by their tendency
      to form intermolecular hydrogen bonds. This includes the effect of pressure on
      the glass transition temperature Tg, changes in the fragility parameter m and
      activation volume DeltaV, the role of thermal energy and density fluctuations in
      governing the viscous liquid dynamics (Ev/Ep ratio). Finally, we have also
      demonstrated that the dynamic behaviour of a single enantiomer and the racemic
      mixture of the same compound are very much alike. Nevertheless, some slight
      differences were observed, particularly in the taualpha(T) dependencies measured
      in the vicinity of glass transition both at ambient and elevated pressure. 

PMID- 27035124
TI  - Inhibition of beta2-adrenergic receptor reduces triple-negative breast cancer
      brain metastases: The potential benefit of perioperative beta-blockade.
AB  - In response to recent studies, we investigated an association between
      perioperative beta-blockade and breast cancer metastases. First, a retrospective
      study examining perioperative beta-blocker use and cancer recurrence and
      metastases was conducted on 1,029 patients who underwent breast cancer surgery at
      the City of Hope Cancer Center between 2000 and 2010. We followed the clinical
      study and examined proliferation, migration, and invasion in vitro of primary and
      brain-metastatic breast cancer cells in response to beta2-activation and
      inhibition. We also investigated in vivo the metastatic potential of propranolol
      treated metastatic cells. For stage II breast cancer patients, perioperative beta
      blockade was associated with decreased cancer recurrence using Cox regression
      analysis (hazard's ratio =0.51; 95% CI: 0.23-0.97; p=0.041). Triple-negative (TN)
      brain-metastatic cells were found to have increased beta2-adrenergic receptor
      mRNA and protein expression relative to TN primary cells. In response to beta2
      adrenergic receptor activation, TN brain-metastatic cells also exhibited
      increased cell proliferation and migration relative to the control. These effects
      were abrogated by propranolol. Propranolol decreased beta2-adrenergic receptor
      activated invasion. In vivo, propranolol treatment of TN brain-metastatic cells
      decreased establishment of brain metastases. Our results suggest that stress and
      corresponding beta2-activation may promote the establishment of brain metastases
      of TN breast cancer cells. In addition, our data suggest a benefit to
      perioperative beta-blockade during surgery-induced stress with respect to breast
      cancer recurrence and metastases. 

PMID- 27035125
TI  - Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory
      response in a rat model of collagen-induced arthritis.
AB  - Rheumatoid arthritis is considered a serious public health problem, which is
      commonly treated with traditional Chinese or herbal medicine. The present study
      evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on
      a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA
      received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly
      suppressed compared with in the model group. In addition, BCBE significantly
      ameliorated pathological joint alterations, including synovial hyperplasia, and
      cartilage and bone destruction. The protein and mRNA expression levels of
      interleukin (IL)-6, IL-8, tumor necrosis factor-alpha and nuclear factor-kappaB
      in synovial tissue were determined by immunohistochemical staining, western blot
      analysis and reverse transcription-polymerase chain reaction. The results
      demonstrated that the expression levels of these factors were significantly
      downregulated in the BCBE-treated group compared with in the model group. These
      results indicated that BCBE may exert an inhibitory effect on the CIA rat model,
      and its therapeutic potential is associated with its anti-inflammatory action. 

PMID- 27035126
TI  - Correlation between insulin-like growth factor binding protein 3 and metastasis
      associated gene 1 protein in esophageal squamous cell carcinoma.
AB  - The present study aimed to investigate the correlation between insulin-like
      growth factor binding protein 3 (IGFBP-3) and metastasis-associated gene 1 (MTA1)
      protein, and the clinicopathological features and prognosis of esophageal
      squamous cell carcinoma (ESCC). Patients with ESCC who underwent surgical
      resection were enrolled in the current study, ESCC tissues and adjacent normal
      tissues (control) were obtained from 197 patients. The protein expression levels
      of IGFBP-3 and MTA1 were detected using immunohistochemistry. The results
      demonstrated that the expression of IGFBP-3 in ESCC tissues was significantly
      lower than in the adjacent normal tissues (27.4 vs. 40.6%; P<0.05), and was
      negatively correlated with smoking status, degree of tumor differentiation and
      lymph node metastasis (P<0.05). The expression of MTA1 protein in ESCC tissues
      was significantly higher than that of the adjacent tissues (42.1 vs. 11.2%;
      P<0.05), and was positively correlated with the tumor size, extent of tumor
      invasion and lymph node metastasis (P<0.05). No association was identified
      between the protein expression levels of IGFBP-3 and MTA1. The protein expression
      levels of IGFBP-3 and MTA1 were not independent risk factors for ESCC prognosis;
      however, the degree of tumor invasion (P=0.02) and rate of lymph node metastasis
      (P=0.027) were. IGFBP-3 inhibits the proliferation and metastasis of ESCC;
      however, MTA1 promotes the proliferation and metastasis of ESCC. There is no
      interaction between IGFBP-3 and MTA1 in ESCC, and they are not independent risk
      factors for ESCC prognosis. 

PMID- 27035127
TI  - Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated
      medium.
AB  - Non-thermal atmospheric pressure plasma has been widely studied in recent years
      in many fields, including cancer treatment. However, its efficiency for inducing
      apoptosis sometimes varies depending on the cell species and experimental
      conditions. The aim of this study was to elucidate what causes these differences
      in responses to plasma treatment. Using four ovarian cancer cell lines, the cell
      density had a markedly negative impact on the proliferation inhibition rate (PIR)
      and it was more obvious in OVCAR-3 and NOS2 cells. Furthermore, TOV21G and ES-2
      cells were drastically sensitive to plasma-activated medium (PAM) compared with
      the other two cell lines. We demonstrated that the proportion of reactive oxygen
      species and cell number had a marked impact on the effect of PAM against ovarian
      cancer cells. Additionally it was suggested that the morphological features of
      cells were also closely related to the sensitivity of cancer cells to the plasma
      treatment. 

PMID- 27035128
TI  - Infections on Temporal Networks--A Matrix-Based Approach.
AB  - We extend the concept of accessibility in temporal networks to model infections
      with a finite infectious period such as the susceptible-infected-recovered (SIR)
      model. This approach is entirely based on elementary matrix operations and
      unifies the disease and network dynamics within one algebraic framework. We
      demonstrate the potential of this formalism for three examples of networks with
      high temporal resolution: networks of social contacts, sexual contacts, and
      livestock-trade. Our investigations provide a new methodological framework that
      can be used, for instance, to estimate the epidemic threshold, a quantity that
      determines disease parameters, for which a large-scale outbreak can be expected. 

PMID- 27035129
TI  - Secondary Hyperparathyroidism in End-Stage Renal Disease: No Longer a Matter for
      Surgeons?
AB  - Hyperphosphatemia, hypocalcemia and vitamin D deficiency are the main factors
      involved in the pathogenesis of secondary hyperparathyroidism (SHPT). Moreover,
      the skeletal resistance to parathyroid hormone is not only a high-turnover bone
      accompanying SHPT, but may also play a crucial role in the onset of low-turnover
      bone disease in uremia. However, a growing body of evidence suggests that other
      hormones play a key role in this disease, such as fibroblast growth factor 23,
      Klotho and sclerostin. SHPT causes both bone-associated and non-skeletal
      consequences, including cardiovascular calcifications. Furthermore, vitamin D and
      calcium (Ca)-containing phosphate binders may increase Ca load. Anyway, the rate
      of parathyroidectomy in end-stage renal disease has greatly decreased during the
      last decade. Is there any room left for surgeons? 

PMID- 27035130
TI  - Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to
      Endotoxic Shock.
AB  - Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential
      for epidermal and orofacial embryonic development. Irf6 is strongly expressed in
      keratinocytes, in which it regulates epidermal proliferation, differentiation,
      and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine
      gene expression was also reported in an epithelial cell line. However, a function
      for Irf6 in innate immune cells was not previously reported. In the present
      study, we investigated the expression and function of Irf6 in bone marrow-derived
      neutrophils and macrophages. We show here, using a conditional knockout of Irf6
      in lysosymeM expressing cells, that Irf6 is required for resistance to LPS
      induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived
      neutrophils exhibited increased chemotactic index and velocity compared with wild
      type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6
      deficient bone marrow-derived macrophages in vitro. These cells also exhibited an
      increased level of phosphorylated IkBa. Collectively, our findings suggest a role
      for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of
      cytokine production. 

PMID- 27035131
TI  - Synergistic Structure in the Speed Dependent Modulation of Muscle Activity in
      Human Walking.
AB  - Recently, a modular organisation has been proposed to simplify control of the
      large number of muscles involved in human walking. Although previous research
      indicates that a single set of modular activation patterns can account for muscle
      activity at different speeds, these studies only provide indirect evidence for
      the idea that speed regulation in human walking is under modular control. Here, a
      more direct approach was taken to assess the synergistic structure that underlies
      speed regulation, by isolating speed effects through the construction of gain
      functions that represent the linear relation between speed and amplitude for each
      point in the time-normalized gait cycle. The activity of 13 muscles in 13
      participants was measured at 4 speeds (0.69, 1.00, 1.31, and 1.61 ms(-1)) during
      treadmill walking. Gain functions were constructed for each of the muscles, and
      gain functions and the activity patterns at 1.00 ms(-1) were both subjected to
      dimensionality reduction, to obtain modular gain functions and modular basis
      functions, respectively. The results showed that 4 components captured most of
      the variance in the gain functions (74.0% +/- 1.3%), suggesting that the
      neuromuscular regulation of speed is under modular control. Correlations between
      modular gain functions and modular basis functions (range 0.58-0.89) and the
      associated synergistic muscle weightings (range 0.6-0.95) were generally high,
      suggesting substantial overlap in the synergistic control of the basic phasing of
      muscle activity and its modulation through speed. Finally, the combined set of
      modular functions and associated weightings were well capable of predicting
      muscle activity patterns obtained at a speed (1.31 ms(-1)) that was not involved
      in the initial dimensionality reduction, confirming the robustness of the
      presently used approach. Taken together, these findings provide direct evidence
      of synergistic structure in speed regulation, and may inspire further work on
      flexibility in the modular control of gait.

PMID- 27035133
TI  - Neuropsychiatric Disturbances, Self-Mutilation and Malingering in the French
      Armies during World War I: War Strain or Cowardice?
AB  - Between 1914 and 1918, war strain appeared under a number of guises and affected,
      to varying extents, the majority of French soldiers. The most frequent form of
      war strain was war psychoneurosis, but war strain also induced more paroxystic
      disorders, such as acute episodes of terror, self-mutilation, induced illnesses
      and even suicide. Fear was the constant companion of soldiers of the Great War:
      soldiers were either able to tame it or overwhelmed by an uncontrollable fear.
      Nonetheless, over the course of the war, some aspects of fear were recognised as
      syndromes. The French health service poorly anticipated the major consequences of
      war strain, as with many other types of injuries. After the establishment of
      wartime neuropsychiatric centres, two main medical stances emerged: listening to
      soldiers empathetically on the one hand and applying more repressive management
      on the other. For many physicians, the psychological consequences of this first
      modern war were synonymous with malingering or cowardice in the face of duty. The
      stance of French military physicians in relation to their command was not
      unequivocal and remained ambivalent, swaying between medico-military collusion
      and empathy towards soldiers experiencing psychological distress. The ubiquity of
      suspected malingering modified the already porous borders between
      neuropsychiatric disorders and disobedience. Several war psychoneurotic soldiers
      were sentenced by councils of war for deserting their posts in the face of the
      enemy and were shot. Many soldiers suspected of self-mutilation or suffering from
      induced illnesses were also sentenced and executed without an expert assessment
      of their wound or their psychological state. 

PMID- 27035132
TI  - Fluorogenic Real-Time Reporters of DNA Repair by MGMT, a Clinical Predictor of
      Antitumor Drug Response.
AB  - Common alkylating antitumor drugs, such as temozolomide, trigger their
      cytotoxicity by methylating the O6-position of guanosine in DNA. However, the
      therapeutic effect of these drugs is dampened by elevated levels of the DNA
      repair enzyme, O6-methylguanine DNA methyltransferase (MGMT), which directly
      reverses this alkylation. As a result, assessing MGMT levels in patient samples
      provides an important predictor of therapeutic response; however, current methods
      available to measure this protein are indirect, complex and slow. Here we
      describe the design and synthesis of fluorescent chemosensors that report
      directly on MGMT activity in a single step within minutes. The chemosensors
      incorporate a fluorophore and quencher pair, which become separated by the MGMT
      dealkylation reaction, yielding light-up responses of up to 55-fold, directly
      reflecting repair activity. Experiments show that the best-performing probe
      retains near-native activity at mid-nanomolar concentrations. A nuclease
      protected probe, NR-1, was prepared and tested in tumor cell lysates,
      demonstrating an ability to evaluate relative levels of MGMT repair activity in
      twenty minutes. In addition, a probe was employed to evaluate inhibitors of MGMT,
      suggesting utility for discovering new inhibitors in a high-throughput manner.
      Probe designs such as that of NR-1 may prove valuable to clinicians in selection
      of patients for alkylating drug therapies and in assessing resistance that arises
      during treatment. 

PMID- 27035134
TI  - Cancer and Obesity in Rhode Island.
AB  - There is growing evidence that obesity increases the risk of certain cancers and
      cancer mortality. As obesity rates are projected to rise over the next decade,
      associated cancer morbidity and mortality present a significant public health
      concern. This is particularly striking in the state of Rhode Island, where nearly
      a third of the population is obese. Interventions such as taxation of obesity
      associated foods or insurance incentive programs promoting positive health
      behaviors could decrease obesity-associated cancer incidence and mortality over
      time. Public health programs could be deployed at both the local and national
      levels. We provide a background on obesity-related cancer, discuss existing
      evidence to support these ideas, and make recommendations regarding individual
      and societal factors when considering public policy, health-care delivery,
      taxation structure, and insurance.

PMID- 27035135
TI  - Palliative and End-of-Life Care Education Among Alpert Medical School Students.
AB  - Doctors in almost every branch of medicine encounter patients who are dying or
      have serious illnesses. Numerous studies, however, indicate that the education of
      physicians does not adequately prepare them for such patients. We aimed to
      characterize the current training of Alpert Medical School (AMS) students on
      palliative and end-of-life care using a cross-sectional, web-administered survey.
      We discovered less than half of Alpert Medical School students have worked with
      dying patients, and almost a quarter of graduating medical students did not feel
      prepared to palliate common symptoms including pain, nausea, shortness of breath,
      and anxiety. We also found that exposure to dying individuals was significantly
      associated with many symptom management skills and more favorable attitudes
      toward palliative medicine. We therefore recommend that palliative care skills,
      which are relevant to all future physicians regardless of specialty, be
      incorporated throughout the AMS curriculum, and that more students be exposed to
      patients at end-of-life.

PMID- 27035136
TI  - A Revised Simulation-Based Cataract Surgery Course for Ophthalmology Residents.

PMID- 27035137
TI  - Persistence with Newly Initiated Antidepressant Medication in Rhode Island
      Medicaid: Analysis and Insights for Promoting Patient Adherence.
AB  - OBJECTIVE: To describe persistence to newly prescribed antidepressant medications
      within the Rhode Island Medicaid population. METHODS: This retrospective study
      analyzed antidepressant medication persistence in a cohort of new users for a
      period spanning 2013-2014, focusing on the acute treatment phase (first 12 weeks
      of treatment). Covariates assessed included patient gender, age, comorbidity
      status, and measures of health system utilization. RESULTS: Only 53.8% of
      patients persisted with medication for at least 12 weeks. (Figure 1). Persistence
      was increased with age > 35, and lower among patients lacking a follow-up visit.
      Multivariable analyses revealed that patients having at least one office visit
      during the follow-up period were nearly 2.5 times more likely to persist as
      compared to patients lacking such visits (OR 2.44, 95% CI 1.77-3.35). Persistence
      was 22% more likely among patients receiving psychiatric services (OR 1.22; 95%
      CI 1.00-1.48). CONCLUSIONS: Antidepressant treatment persistence within the R.I.
      Medicaid population is suboptimal, and lowest among patients lacking follow-up
      care.

PMID- 27035138
TI  - Migraine with unilateral mydriasis.

PMID- 27035139
TI  - A Case of Hypothermia.

PMID- 27035140
TI  - Active and Direct Active Monitoring of Travelers Returning from Countries that
      Experienced Widespread Transmission of Ebola Virus Disease, Rhode Island, October
      2014-December 2015.

PMID- 27035141
TI  - Pain management: Considering the medical, legal aspects in patient care.

PMID- 27035142
TI  - Medical Passports.

PMID- 27035143
TI  - A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation
      in the Retina.
AB  - Implantable electrode arrays are widely used in therapeutic stimulation of the
      nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most
      neural prostheses use serial stimulation (i.e. one electrode at a time) despite
      this severely limiting the repertoire of stimuli that can be applied. Methods to
      reliably predict the outcome of multi-electrode stimulation have not been
      available. Here, we demonstrate that a linear-nonlinear model accurately predicts
      neural responses to arbitrary patterns of stimulation using in vitro recordings
      from single retinal ganglion cells (RGCs) stimulated with a subretinal multi
      electrode array. In the model, the stimulus is projected onto a low-dimensional
      subspace and then undergoes a nonlinear transformation to produce an estimate of
      spiking probability. The low-dimensional subspace is estimated using principal
      components analysis, which gives the neuron's electrical receptive field (ERF),
      i.e. the electrodes to which the neuron is most sensitive. Our model suggests
      that stimulation proportional to the ERF yields a higher efficacy given a fixed
      amount of power when compared to equal amplitude stimulation on up to three
      electrodes. We find that the model captures the responses of all the cells
      recorded in the study, suggesting that it will generalize to most cell types in
      the retina. The model is computationally efficient to evaluate and, therefore,
      appropriate for future real-time applications including stimulation strategies
      that make use of recorded neural activity to improve the stimulation strategy. 

PMID- 27035144
TI  - The Tyrosine Kinase Inhibitor Sunitinib Affects Ovulation but Not Ovarian Reserve
      in Mouse: A Preclinical Study.
AB  - The aim of the study was to evaluate ovarian toxicity of tyrosine kinase
      inhibitor (TKI) sunitinib, since only scarce data are available on gonadal
      function after this treatment. Six-week-old female mice received orally, once
      daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks. Fertility parameters
      were analyzed from ovulation to litter assessment. Sunitinib exposure
      significantly reduced (i) corpora lutea number per ovary (1.1 +/- 0.38 in
      sunitinib group versus 4 +/- 0.79 in control group, p<0.01) and (ii) serum Anti
      Mullerian hormone (AMH) levels in sunitinib treated mice (12.01 +/- 1.16)
      compared to control mice (14.33 +/- 0.87 ng/ml, p< 0.05). However, primordial and
      growing follicles numbers per ovary were not different in both groups. After
      treatment withdrawal, female mice in both groups were able to obtain litters.
      These data could be helpful to counsel clinicians and patients, when fertility
      preservation methods are discussed, before TKI treatment in girls and young
      women. 

PMID- 27035145
TI  - Serum Levels of Polybrominated Diphenyl Ethers in Girls with Premature Thelarche.
AB  - BACKGROUND/AIMS: Polybrominated diphenyl ethers (PBDEs) are widely used as flame
      retardants and have shown endocrine disruption properties in experimental
      studies. The aim of this study was to investigate the association between the
      exposure to PBDEs and alterations of puberty in girls referred for idiopathic
      central precocious puberty (ICPP) and premature thelarche (PT). METHODS: A case
      control study was conducted in 124 girls: 37 girls with ICPP (mean age 7.4 +/-
      0.9 years), 56 with PT (mean age 5.7 +/- 2.1 years) and 31 controls (mean age 5.4
      +/- 1.9 years). PBDE serum concentrations, hormone levels and anthropometry were
      assessed. PBDE concentrations were corrected for total serum lipid content.
      Individual exposure to PBDEs was evaluated through ad hoc questionnaires.
      RESULTS: PBDE serum concentrations corrected for total lipid content were
      significantly higher in girls with PT (mean 1.49 +/- 0.63 log ng/g) than in
      controls (mean 1.23 +/- 0.54 log ng/g; p < 0.05). PT girls showed higher levels
      of PBDE than ICPP girls (1.49 +/- 0.63 vs. 1.37 +/- 0.49 log ng/g), though this
      was not significant. An analysis of the questionnaires revealed no significant
      differences in exposure between the three groups. CONCLUSION: Our findings
      suggest that higher concentrations of serum PBDEs are associated with PT in
      girls.

PMID- 27035146
TI  - Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological
      Confirmation of Chagas Disease.
AB  - BACKGROUND: Chagas disease is due to the parasite Trypanosoma cruzi, a protist
      disseminated by a Triatome vector. This disease is endemic to Latin America and
      considered by WHO as one of the 17 world's neglected diseases. In Europe and in
      North America, imported cases are also detected, due to migration of population
      outside of the endemic region. Diagnosis of T. cruzi infection is usually made
      indirectly by the detection of specific antibodies to T. cruzi antigens.
      Following initial diagnostic evaluation or screening test (qualifying or
      discarding blood donation), a confirmation test is performed for samples
      initially reactive. The test presented in this study aims at the
      confirmation/refutation of the infectious status of human blood samples and will
      permit taking appropriate clinical measures. METHODOLOGY/PRINCIPAL FINDINGS: We
      designed a novel array of twelve antigens and printed these antigens onto 96-well
      plates. We tested 248 positive samples T. cruzi, 94 unscreened blood donors'
      samples from non-endemic area, 49 seronegative blood donors, 7 false-positive and
      3 doubtful samples. The observed reactivities were analyzed to propose a decision
      tree algorithm that correctly classifies all the samples, with the potential to
      discriminate false-positive results and sticky samples. We observed that
      antibodies levels (Sum of all antigens) was significantly higher for PCR positive
      than for PCR negative samples in all studied groups with Multi-cruzi.
      CONCLUSION/SIGNIFICANCE: The results described in this study indicate that the
      Multi-cruzi improves the serological confirmation of Chagas disease. Moreover the
      "sum of all antigens" detected by Multi-cruzi could reflect parasitemia level in
      patients-like PCR signals does-and could serve as an indicator of parasite
      clearance in longitudinal follow-ups. Validation of this assay is still required
      on an independent large collection of well characterized samples including
      typical false-reactive samples such as Leishmaniasis.

PMID- 27035147
TI  - Excess of Yra1 RNA-Binding Factor Causes Transcription-Dependent Genome
      Instability, Replication Impairment and Telomere Shortening.
AB  - Yra1 is an essential nuclear factor of the evolutionarily conserved family of
      hnRNP-like export factors that when overexpressed impairs mRNA export and cell
      growth. To investigate further the relevance of proper Yra1 stoichiometry in the
      cell, we overexpressed Yra1 by transforming yeast cells with YRA1 intron-less
      constructs and analyzed its effect on gene expression and genome integrity. We
      found that YRA1 overexpression induces DNA damage and leads to a transcription
      associated hyperrecombination phenotype that is mediated by RNA:DNA hybrids. In
      addition, it confers a genome-wide replication retardation as seen by reduced
      BrdU incorporation and accumulation of the Rrm3 helicase. In addition, YRA1
      overexpression causes a cell senescence-like phenotype and telomere shortening.
      ChIP-chip analysis shows that overexpressed Yra1 is loaded to transcribed
      chromatin along the genome and to Y' telomeric regions, where Rrm3 is also
      accumulated, suggesting an impairment of telomere replication. Our work not only
      demonstrates that a proper stoichiometry of the Yra1 mRNA binding and export
      factor is required to maintain genome integrity and telomere homeostasis, but
      suggests that the cellular imbalance between transcribed RNA and specific RNA
      binding factors may become a major cause of genome instability mediated by co
      transcriptional replication impairment. 

PMID- 27035148
TI  - A Follow-Up Study of 50 Chronic Hepatitis C Patients: Adiponectin as a Resilience
      Biomarker for Major Depression.
AB  - OBJECTIVE: Major depression (MD) is a condition associated with both hepatitis C
      virus (HCV) infection and pegylated interferon (IFN)-alpha treatment. IFN induces
      a depressive syndrome that is associated with an inflammatory profile. We aimed
      to investigate whether there is any specific alteration in plasma biomarkers
      associated with MD. METHODS: HCV-monoinfected patients, with and without IFN
      treatment, were followed up for 18 months and went through structured psychiatric
      evaluation. We assessed plasma levels of brain-derived neurotrophic factor, tumor
      necrosis factor (TNF) and its soluble type 1 and type 2 receptors (sTNFR1 and
      sTNFR2, respectively), and adipokines (adiponectin, leptin and resistin) using
      ELISA. RESULTS: Among the 50 patients included in the study, 14 were treated with
      IFN during the follow-up. Being older, not married, presenting higher body mass
      index, higher liver inflammatory activity, lower baseline adiponectin levels and
      use of IFN were associated with MD development. Higher levels of sTNFR1 during
      IFN treatment were associated with sustained virological response. The lack of a
      control group without HCV infection did not allow any assumption of a biomarker
      change exclusively due to the infection itself. CONCLUSION: Adiponectin may be a
      resilience biomarker for MD in HCV-infected patients.

PMID- 27035149
TI  - Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval
      Involvement in a Pregnant Woman.
AB  - In this article, we report the case of a woman in whom was found an abdominal
      mass during pregnancy and who underwent nephrectomy and extraction of the emboli
      after delivery. The kidney had a volume of 15 * 10 * 8 cm and pathological
      diagnosis was primary Ewing's sarcoma. The patient was treated with conventional
      chemotherapy for 1 year after surgery, at which time multiple metastases were
      found. From this case, we surmise that hormonal changes that occur during
      pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting
      that renal tumors in pregnant women demand serious attention and that anti-cancer
      treatment should begin as soon as possible.

PMID- 27035150
TI  - Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced
      Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis.
AB  - This study aimed to explore the effects of fucoidan from Fucus vesiculosus on
      concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with
      fucoidan protected liver function indicated by ALT, AST and histopathological
      changes by suppressing inflammatory cytokines, such as tumor necrosis factor
      alpha (TNF-alpha) and interferon gamma (IFN-gamma). In addition, intrinsic and
      extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9
      were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and
      JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus
      vesiculosus alleviated ConA-induced acute liver injury via the inhibition of
      intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1
      pathways which were activated by TNF-alpha and IFN-gamma. These findings could
      provide a potential powerful therapy for T cell-related hepatitis. 

PMID- 27035151
TI  - Ephrin-B/EphB Signaling Is Required for Normal Innervation of Lingual Gustatory
      Papillae.
AB  - The innervation of taste buds is an excellent model system for studying the
      guidance of axons during targeting because of their discrete nature and the high
      fidelity of innervation. The pregustatory epithelium of fungiform papillae is
      known to secrete diffusible axon guidance cues such as BDNF and Sema3A that
      attract and repel, respectively, geniculate ganglion axons during targeting, but
      diffusible factors alone are unlikely to explain how taste axon terminals are
      restricted to their territories within the taste bud. Nondiffusible cell surface
      proteins such as Ephs and ephrins can act as receptors and/or ligands for one
      another and are known to control axon terminal positioning in several parts of
      the nervous system, but they have not been studied in the gustatory system. We
      report that ephrin-B2 linked beta-galactosidase staining and immunostaining was
      present along the dorsal epithelium of the mouse tongue as early as embryonic day
      15.5 (E15.5), but was not detected at E14.5, when axons first enter the
      epithelium. Ephrin-B1 immunolabeling was barely detected in the epithelium and
      found at a somewhat higher concentration in the mesenchyme subjacent to the
      epithelium. EphB1 and EphB2 were detected in lingual sensory afferents in vivo
      and geniculate neurites in vitro. Ephrin-B1 and ephrin-B2 were similarly
      effective in repelling or suppressing outgrowth by geniculate neurites in vitro.
      These in vitro effects were independent of the neurotrophin used to promote
      outgrowth, but were reduced by elevated levels of laminin. In vivo, mice null for
      EphB1 and EphB2 exhibited decreased gustatory innervation of fungiform papillae.
      These data provide evidence that ephrin-B forward signaling is necessary for
      normal gustatory innervation of the mammalian tongue.

PMID- 27035152
TI  - Publications on Peripheral Nerve Injuries during World War I: A Dramatic Increase
      in Knowledge.
AB  - Publications from French (Jules Tinel and Chiriachitza Athanassio-Benisty),
      English (James Purves-Stewart, Arthur Henry Evans and Hartley Sidney Carter),
      German (Otfrid Foerster and Hermann Oppenheim) and American (Charles Harrison
      Frazier and Byron Stookey) physicians from both sides of the front during World
      War I (WWI) contributed to a dramatic increase in knowledge about peripheral
      nerve injuries. Silas Weir Mitchell's original experience with respect to these
      injuries, and particularly causalgia, during the American Civil War was further
      expanded in Europe during WWI. Following the translation of one of his books, he
      was referred to mainly by French physicians. During WWI, several French books
      were in turn translated into English, which influenced American physicians, as
      was observed in the case of Byron Stookey. The establishment of neurological
      centres played an important role in the concentration of experience and
      knowledge. Several eponyms originated during this period (including the Hoffmann
      Tinel sign and the Froment sign). Electrodiagnostic tools were increasingly used.

PMID- 27035153
TI  - Studies Need More than a Spot Sample: Variability of Urinary Metal Levels over
      Time.

PMID- 27035154
TI  - Informing 21st-Century Risk Assessments with 21st-Century Science.
AB  - Understanding and preventing adverse impacts from chemicals in the environment is
      fundamental to protecting public health, and chemical risk assessments are used
      to inform public health decisions in the United States and around the world.
      Traditional chemical risk assessments focus on health effects of environmental
      contaminants on a chemical-by-chemical basis, largely based on data from animal
      models using exposures that are typically higher than those experienced by
      humans. Results from environmental epidemiology studies sometimes show effects
      that are not observed in animal studies at human exposure levels that are lower
      than those used in animal studies. In addition, new approaches such as Toxicology
      in the 21st Century (Tox21) and exposure forecasting (ExpoCast) are generating
      mechanistic data that provide broad coverage of chemical space, chemical
      mixtures, and potential associated health outcomes, along with improved exposure
      estimates. It is becoming clear that risk assessments in the future will need to
      use the full range of available mechanistic, animal, and human data to integrate
      multiple types of data and to consider nontraditional health outcomes and end
      points. This perspective was developed at the "Strengthening the Scientific Basis
      of Chemical Safety Assessments" workshop, which was cosponsored by the U.S.
      Environmental Protection Agency and the National Institute of Environmental
      Health Sciences, where gaps between the emerging science and traditional chemical
      risk assessments were explored, and approaches for bridging the gaps were
      considered.

PMID- 27035155
TI  - Increased incidence of invasive meningococcal disease of serogroup C / clonal
      complex 11, Tuscany, Italy, 2015 to 2016.
AB  - We report an increase of serogroup C Neisseria meningitidis invasive
      meningococcal disease in Tuscany. From January 2015 to end February 2016, 43
      cases were reported, among which 10 were fatal, compared to two cases caused by
      serogroup C recorded in 2014 and three in 2013. No secondary cases occurred.
      Thirty-five strains belonged to C:P1.5-1,10-8:F3-6:ST-11(cc11). Control measures
      have been adopted and immunisation campaigns implemented. Studies on risk factors
      and carriage are ongoing. 

PMID- 27035156
TI  - Partial Unfolding of Tubulin Heterodimers Induced by Two-Photon Excitation of
      Bound meso-Tetrakis(sulfonatophenyl)porphyrin.
AB  - The water-soluble porphyrin meso-tetrakis(p-sulfonatophenyl)porphyrin (TSPP) can
      be noncovalently bound to tubulin and used as a photosensitizer, which upon
      irradiation triggers photochemical reactions that lead to conformational changes
      of the protein. These conformational changes in turn inhibit tubulin's primary
      function of polymerizing into microtubules. We explored the possibility of using
      two-photon excitation of the bound porphyrin to induce photosensitized protein
      unfolding. Although TSPP has a relatively low cross section (~30 GM) our results
      did find that two-photon excitation of the ligand causes partial unfolding of the
      tubulin host and the inhibition of the in vitro formation of microtubules.
      Conversely, irradiating tubulin alone caused no such effects despite the large
      irradiance per pulse (97-190 GW/cm(2)). The conformational changes were
      characterized using spectroscopic studies and provide a promising protocol for
      the future application of non-native photosensitization of proteins.

PMID- 27035158
TI  - Dissolution rates of over-the-counter painkillers: a comparison among
      formulations.
AB  - BACKGROUND: We wanted to compare the dissolution profile of several over-the
      counter analgesics to understand whether the different formulation techniques
      employed to enhance absorption were associated with variations in the dissolution
      rate, a parameter known to affect drug absorption. METHODS: We considered 5
      formulations currently marketed in Italy: aspirin tablets (Aspirina Dolore e
      Infiammazione(r)), ibuprofen tablets and liquid capsules (Moment(r)), ibuprofen
      lysine tablets (Nurofenimmedia(r)) and dexketoprofen trometamol tablets
      (Enantyum(r)). Dissolution tests were performed according to the current USP/NF
      monograph dissolution procedure. Drug dissolution was evaluated at 1, 3, 6, 15,
      and 30 minutes since the start of the test. Dissolution was evaluated at three
      different pH: 1.2, 4.5 and 6.8. Every test was repeated 12 times. RESULTS: The
      aspirin formulation was by far the most rapid dissolving formulation, among those
      tested, with more than 80% of the tablet dissolved at 6 minutes for every pH
      considered. At pH 1.2 and 4.5, only the dexketoprofen formulation was able to
      reach the dissolution level of aspirin at 30 minutes, but had lower levels of
      dissolution at the previous time points. Instead, at pH 6.8, most of the
      formulations approached aspirin dissolution level, but only after 15 minutes.
      Ibuprofen capsules had the slowest kinetics, with a lag phase the first 6
      minutes. CONCLUSIONS: Different formulation strategies can lead to great
      differences in the dissolution rates even among drugs of the same class,
      suggesting that enhancements in the formulation of painkillers can lead to
      improvements in drug absorption, and thus in the onset of analgesia.

PMID- 27035157
TI  - A Multicenter, Rater-Blinded, Randomized Controlled Study of Auditory Processing
      Focused Cognitive Remediation Combined With Open-Label Lurasidone in Patients
      With Schizophrenia and Schizoaffective Disorder.
AB  - OBJECTIVE: Small-scale studies of auditory processing cognitive remediation
      programs have demonstrated efficacy in schizophrenia. We describe a multicenter,
      rater-blinded, randomized, controlled study of auditory-focused cognitive
      remediation, conducted from June 24, 2010, to June 14, 2013, and approved by the
      local institutional review board at all sites. METHOD: Prior to randomization,
      participants with schizophrenia (DSM-IV-TR) were stabilized on a standardized
      antipsychotic regimen (lurasidone [40-160 mg/d]), followed by randomization to
      adjunctive cognitive remediation: auditory focused (Brain Fitness) versus control
      (nonspecific video games), administered 1-2 times weekly for 30 sessions.
      Coprimary outcome measures included MATRICS Consensus Cognitive Battery (MCCB)
      and the University of California, San Diego, Performance-Based Skills Assessment
      Brief scale. RESULTS: 120 participants were randomized and completed at least 1
      auditory-focused cognitive remediation (n = 56) or video game control session (n
      = 64). 74 participants completed >= 25 sessions and postrandomization
      assessments. At study completion, the change from prestabilization was
      statistically significant for MCCB composite score (d = 0.42, P < .0001) across
      groups. Participants randomized to auditory-focused cognitive remediation had a
      trend-level higher mean MCCB composite score compared to participants randomized
      to control cognitive remediation (P = .08). After controlling for scores at the
      time of randomization, there were no significant between-treatment group
      differences at study completion. CONCLUSIONS: Auditory processing cognitive
      remediation combined with lurasidone did not lead to differential improvement
      over nonspecific video games. Across-group improvement from prestabilization
      baseline to study completion was observed, but since all participants were
      receiving lurasidone open label, it is difficult to interpret the source of these
      effects. Future studies comparing both pharmacologic and behavioral cognitive
      enhancers should consider a 2 * 2 design, using a control for both the medication
      and the cognitive remediation. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01173874.

PMID- 27035159
TI  - Efficacy outcomes from 3 clinical trials of edivoxetine as adjunctive treatment
      for patients with major depressive disorder who are partial responders to
      selective serotonin reuptake inhibitor treatment.
AB  - OBJECTIVE: Three studies examined whether edivoxetine (a highly selective
      norepinephrine reuptake inhibitor) had efficacy as adjunctive therapy for
      patients with major depressive disorder (DSM-IV-TR) who were partial responders
      to selective serotonin reuptake inhibitor (SSRI) treatment of at least 6 weeks'
      duration. METHOD: Studies were 8-week randomized, placebo-controlled trials with
      a 3-week double-blind placebo lead-in phase, conducted from December 16, 2010, to
      October 21, 2013. Patients entered the double-blind adjunctive treatment phase if
      they met randomization criteria (< 25% improvement on Montgomery-Asberg
      Depression Rating Scale [MADRS] and MADRS total score >= 14); patients not
      randomized remained on adjunctive placebo. Study 1 compared fixed-dose
      edivoxetine (12 or 18 mg daily) + SSRI (N = 231 and N = 230, respectively) with
      placebo + SSRI (N = 240); study 2 compared flexible-dose edivoxetine (12-18 mg
      daily) + SSRI (N = 232) and fixed-dose edivoxetine (6 mg daily) + SSRI (N = 226)
      with placebo + SSRI (N = 231); and study 3 compared flexible-dose edivoxetine (12
      18 mg daily) + SSRI (N = 230) with placebo + SSRI (N = 219). The primary outcome
      was mean change from randomization baseline to week 8 in MADRS total score,
      analyzed using repeated measures analysis. RESULTS: Each trial failed to meet the
      primary and most of the secondary objectives. The least-squares mean changes in
      MADRS total score were as follows-study 1: -8.5 (edivoxetine 12 mg + SSRI), -8.7
      (edivoxetine 18 mg + SSRI), and -7.8 (placebo + SSRI); study 2: -9.4 (edivoxetine
      12-18 mg + SSRI), -9.6 (edivoxetine 6 mg + SSRI), and -9.4 (placebo + SSRI); and
      study 3: -8.7 (edivoxetine 12-18 mg + SSRI) and -8.5 (placebo + SSRI).
      CONCLUSIONS: Adjunctive edivoxetine treatment for patients with major depressive
      disorder who were partial responders to SSRIs did not significantly improve
      efficacy outcomes. TRIALS REGISTRATIONS: ClinicalTrials.gov identifiers:
      NCT01173601, NCT01187407, NCT01185340.

PMID- 27035160
TI  - Salinomycin causes migration and invasion of human fibrosarcoma cells by inducing
      MMP-2 expression via PI3-kinase, ERK-1/2 and p38 kinase pathways.
AB  - Salinomycin (SAL) is a polyether ionophore antibiotic that has recently been
      shown to regulate a variety of cellular responses in various human cancer cells.
      However, the effects of SAL on metastatic capacity of HT1080 human fibrosarcoma
      cells have not been elucidated. We investigated the effect of SAL on migration
      and invasion, with emphasis on the expression and activation of matrix
      metalloproteinase (MMP)-2 in HT1080 human fibrosarcoma cells. Treatment of SAL
      promoted the expression and activation of MMP-2 in a dose- and time-dependent
      manner, as detected by western blot analysis, gelatin zymography, and real-time
      polymerase chain reaction. SAL also increased metastatic capacities, as
      determined by an increase in the migration and invasion of cells using the wound
      healing assay and the invasion assay, respectively. To confirm the detailed
      molecular mechanisms of these effects, we measured the activation of
      phosphoinositide 3 kinase (PI3-kinase) and mitogen-activated protein kinase
      (MAPK)s (ERK-1/2 and p38 kinase), as detected by the phosphorylated proteins
      through western blot analysis. SAL treatment increased the phosphorylation of Akt
      and MAPKs. Inhibition of PI3-kinase, ERK-1/2, and p38 kinase with LY294002,
      PD98059, and SB203580, respectively, in the presence of SAL suppressed the
      metastatic capacity by reducing MMP-2 expression, as determined by gelatin
      zymography. Our results indicate that the PI3-kinase and MAPK signaling pathways
      are involved in migration and invasion of HT1080 through induction of MMP-2
      expression and activation. In conclusion, SAL significantly increases the
      metastatic capacity of HT1080 cells by inducing MMP-2 expression via PI3-kinase
      and MAPK pathways. Our results suggest that SAL may be a potential agent for the
      study of cancer metastatic capacities. 

PMID- 27035161
TI  - Myogenic differentiation potential of human tonsil-derived mesenchymal stem cells
      and their potential for use to promote skeletal muscle regeneration.
AB  - Stem cells are regarded as an important source of cells which may be used to
      promote the regeneration of skeletal muscle (SKM) which has been damaged due to
      defects in the organization of muscle tissue caused by congenital diseases,
      trauma or tumor removal. In particular, mesenchymal stem cells (MSCs), which
      require less invasive harvesting techniques, represent a valuable source of cells
      for stem cell therapy. In the present study, we demonstrated that human tonsil
      derived MSCs (T-MSCs) may differentiate into myogenic cells in vitro and that the
      transplantation of myoblasts and myocytes generated from human T-MSCs mediates
      the recovery of muscle function in vivo. In order to induce myogenic
      differentiation, the T-MSC-derived spheres were cultured in Dulbecco's modified
      Eagle's medium/nutrient mixture F-12 (DMEM/F-12) supplemented with 1 ng/ml
      transforming growth factor-beta, non-essential amino acids and insulin
      transferrin-selenium for 4 days followed by culture in myogenic induction medium
      [low-glucose DMEM containing 2% fetal bovine serum (FBS) and 10 ng/ml insulin
      like growth factor 1 (IGF1)] for 14 days. The T-MSCs sequentially differentiated
      into myoblasts and skeletal myocytes, as evidenced by the increased expression of
      skeletal myogenesis-related markers [including alpha-actinin, troponin I type 1
      (TNNI1) and myogenin] and the formation of myotubes in vitro. The in situ
      transplantation of T-MSCs into mice with a partial myectomy of the right
      gastrocnemius muscle enhanced muscle function, as demonstrated by gait assessment
      (footprint analysis), and restored the shape of SKM without forming teratomas.
      Thus, T-MSCs may differentiate into myogenic cells and effectively regenerate SKM
      following injury. These results demonstrate the therapeutic potential of T-MSCs
      to promote SKM regeneration following injury.

PMID- 27035162
TI  - Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1
      and CD44 via autophagy in non-small lung cancer.
AB  - Acquired resistance to standard chemotherapy causes treatment failure in patients
      with local advanced and advanced non-small lung cancer (NSCLC). Cancer stem cells
      (CSCs) are a small subpopulation within cancer that is thought to be resistant to
      conventional chemotherapy. The Notch pathway is one of the most intensively
      studied for putative therapeutic targets of CSCs in solid tumors. In our study,
      suppression of Notch3 decreased colony and sphere formation of stem-like property
      in lung cancer cells. In addition, Notch3 expression was demonstrated to be
      upregulated in the patients with chemoresistance and related to poor prognosis of
      NSCLC patients. Our results also showed that CSC markers ALDH1A1 and CD44 were
      highly expressed in NSCLC patients with chemoresistance and these two markers
      were positively correlated with Notch3 expression in lung cancer specimens from
      TCGA database. Furthermore, the lung cancer cells with drug resistance were shown
      to be associated with activation of autophagy. All the data support a crucial
      role of Notch3 in the increase of stem-like property in NSCLC cells that might be
      associated with upregulation of ALDH1A1 and CD44 and activation of autophagy. 

PMID- 27035163
TI  - Structural Phase Transitions and Metallized Phenomena in Arsenic Telluride under
      High Pressure.
AB  - In this study, first-principle calculations, in situ angle-dispersive X-ray
      diffraction, and in situ electrical resistance measurements were performed on
      arsenic telluride (As2Te3) under high pressure. Structural phase transitions and
      metallized phenomena were observed from the calculated and experimental results.
      Upon compression, alpha-As2Te3 transforms into phases alpha' and alpha" at ~5.09
      and ~13.2 GPa, respectively, with two isostructural phase transitions. From 13.2
      GPa, As2Te3 starts to transform into phase gamma, with one first-order monoclinic
      to monoclinic crystal structural phase transition. According to the first
      principle calculations and electrical resistance measurements, the structural
      phase transitions in the compression process induce the transformation from an
      insulator (phase alpha) across a semimetal (phase alpha') into a metal (phases
      alpha" and gamma). The evolution of the structure and transport property upon
      compression on As2Te3 is helpful for understanding the properties of other A2B3
      type compounds under high pressure. 

PMID- 27035165
TI  - Patterns of recurrence and survival in sporadic, neurofibromatosis Type 1
      associated, and radiation-associated malignant peripheral nerve sheath tumors.
AB  - OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive
      group of soft tissue sarcomas that can arise sporadically, in the context of
      neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series
      profiling the features and outcomes of sporadic, NF1-associated, and radiation
      associated MPNSTs are limited. The goal of this study was to elucidate
      differences between MPNST etiologies in a large single-institution retrospective
      study. METHODS Patients (n = 317) were identified through the tumor registry of
      The University of Texas MD Anderson Cancer Center. Clinicopathological features
      were retrospectively collected. Features were compared among MPNST subtypes for
      patients who had sufficient clinical history (n = 289), and clinicopathological
      features were used to identify adverse predictors of recurrence and survival
      outcomes. RESULTS Five-year local recurrence-free survival (LRFS), distant
      recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates
      were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five
      year DSS was lower in NF1-associated and radiation-associated MPNST than in
      sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with
      radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and
      NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs
      NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins,
      local recurrence, and metastasis were predictors of adverse DSS in multivariate
      analysis. CONCLUSIONS Radiation-associated MPNSTs are associated with poorer
      local recurrence-free and disease-specific survival than sporadic and NF1
      associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing
      to large tumor size, compromising truncal location, and lower rate of negative
      resection margins compared with sporadic tumors.

PMID- 27035164
TI  - Convection-enhanced delivery in glioblastoma: a review of preclinical and
      clinical studies.
AB  - Glioblastoma is the most common malignant brain tumor, and it carries an
      extremely poor prognosis. Attempts to develop targeted therapies have been
      hindered because the blood-brain barrier prevents many drugs from reaching tumors
      cells. Furthermore, systemic toxicity of drugs often limits their therapeutic
      potential. A number of alternative methods of delivery have been developed, one
      of which is convection-enhanced delivery (CED), the focus of this review. The
      authors describe CED as a therapeutic measure and review preclinical studies and
      the most prominent clinical trials of CED in the treatment of glioblastoma. The
      utilization of this technique for the delivery of a variety of agents is covered,
      and its shortcomings and challenges are discussed in detail.

PMID- 27035166
TI  - Interhemispheric connectivity revealed by diffusion tensor imaging fiber tracking
      derived from navigated transcranial magnetic stimulation maps as a sign of
      language function at risk in patients with brain tumors.
AB  - OBJECTIVE Resection of brain tumors in language-eloquent areas entails the risk
      of postoperative aphasia. It has been demonstrated via navigated transcranial
      magnetic stimulation (nTMS) that language function can partially shift to the
      unaffected hemisphere due to tumor-induced plasticity. Therefore, this study was
      designed to evaluate whether interhemispheric connectivity (IC) detected by nTMS
      based diffusion tensor imaging-fiber tracking (DTI-FT) can be used to predict
      surgery-related aphasia in patients with brain tumors. METHODS Thirty-eight
      patients with left-sided perisylvian brain lesions underwent cortical language
      mapping of both hemispheres by nTMS prior to awake surgery. Then, nTMS-based DTI
      FT was conducted with a fractional anisotropy (FA) of 0.01 and 0.2 to visualize
      nTMS-based IC. Receiver operating characteristics were calculated for the
      prediction of a postoperative (irrespective of the preoperative state) and a new
      surgery-related aphasia by the presence of detectable IC. RESULTS Language
      mapping by nTMS was possible in all patients. Seventeen patients (44.7%) suffered
      from surgery-related worsening of language performance (transient aphasia
      according to 3-month follow-up in 16 subjects [42.1%]; new permanent aphasia
      according to 3-month follow-up in 1 patient [2.6%]). Regarding the correlation of
      aphasia to nTMS-based IC, statistically significant differences were revealed for
      both evaluated FA values. However, better results were observed for tractography
      with an FA of 0.2, which led to a specificity of 93% (postoperative aphasia) and
      90% (surgery-related aphasia). For postoperative aphasia, the corresponding OR
      was 0.1282 (95% CI 0.0143-1.1520), and for surgery-related aphasia the OR was
      0.1184 (95% CI 0.0208-0.6754). CONCLUSIONS According to these results, IC
      detected by preoperative nTMS-based DTI-FT might be regarded as a risk factor for
      surgery-related aphasia, with a specificity of up to 93%. However, because the
      majority of enrolled patients suffered from transient aphasia postoperatively, it
      has to be evaluated whether this approach distinctly leads to similar results
      among patients with permanent language deficits. Despite this restriction, this
      approach might contribute to individualized patient consultation prior to tumor
      resection in clinical practice.

PMID- 27035167
TI  - Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder:
      converging evidence from cognitive neuroscience and psychiatric neurosurgery.
AB  - OBJECTIVE Advances in understanding the neurobiological basis of psychiatric
      disorders will improve the ability to refine neuromodulatory procedures for
      treatment-refractory patients. One of the core dysfunctions in obsessive
      compulsive disorder (OCD) is a deficit in cognitive control, especially involving
      the dorsal anterior cingulate cortex (dACC). The authors' aim was to derive a
      neurobiological understanding of the successful treatment of refractory OCD with
      psychiatric neurosurgical procedures targeting the dACC. METHODS First, the
      authors systematically conducted a review of the literature on the role of the
      dACC in OCD by using the search terms "obsessive compulsive disorder" and
      "anterior cingulate." The neuroscience literature on cognitive control mechanisms
      in the dACC was then combined with the literature on psychiatric neurosurgical
      procedures targeting the dACC for the treatment of refractory OCD. RESULTS The
      authors reviewed 89 studies covering topics that included structural and
      functional neuroimaging and electrophysiology. The majority of resting-state
      functional neuroimaging studies demonstrated dACC hyperactivity in patients with
      OCD relative to that in controls, while task-based studies were more variable.
      Electrophysiological studies showed altered dACC-related biomarkers of cognitive
      control, such as error-related negativity in OCD patients. These studies were
      combined with the cognitive control neurophysiology literature, including the
      recently elaborated expected value of control theory of dACC function. The
      authors suggest that a central feature of OCD pathophysiology involves the
      generation of mis-specified cognitive control signals by the dACC, and they
      elaborate on this theory and provide suggestions for further study. CONCLUSIONS
      Although abnormalities in brain structure and function in OCD are distributed
      across a wide network, the dACC plays a central role. The authors propose a
      theory of cognitive control dysfunction in OCD that attempts to explain the
      therapeutic efficacy of dACC neuromodulation. This theoretical framework should
      help to guide further research into targeted treatments of OCD and other
      disorders of cognitive control.

PMID- 27035168
TI  - Risk factors for hemorrhage associated with external ventricular drain placement
      and removal.
AB  - OBJECTIVE External ventricular drains (EVDs) have an important role in the
      management of neurological disease, and their placement is a frequently performed
      neurosurgical procedure. Hemorrhage is a common complication of EVD placement and
      occurs more frequently than originally believed. There is also risk of hemorrhage
      with removal of an EVD, which has not been well described. The authors
      investigated the risk factors associated with placement and removal of EVDs at
      their institution. METHODS A database was created including patients who required
      EVD placement from March 2008 to June 2014 at the University of Minnesota. A
      retrospective chart review was completed, and data were collected for each
      patient. All cranial imaging studies during the index hospitalization were
      reviewed to identify hemorrhages associated with either EVD placement or removal.
      The study was performed using a research protocol approved by the University of
      Minnesota's institutional review board. RESULTS Four hundred eighty-two EVDs were
      placed during the designated time period. Among the cases in which patients
      underwent imaging after the placement procedure, hemorrhage was found in 94
      (21.6%). The hemorrhage volume ranged from 0.003 cm3 to 45.9 cm3 (mean [+/- SD]
      1.96 +/- 6.48 cm3). Two of these hemorrhages resulted in additional
      interventions: 1 surgical evacuation and 1 contralateral EVD. In 55 (22.5%) of
      the 244 cases in which imaging was performed after EVD removal, hemorrhage
      associated with removal was identified. The mean volume of these hemorrhages was
      8.25 +/- 20.34 cm3 (range 0.012-82.08 cm3). Two EVDs were replaced, and 1 patient
      died as a result of a large hemorrhage. Large hemorrhages (> 30 cm3) occurred in
      2 patients on placement (0.46%) and in 5 patients on removal (2.0%). In this
      series, decreased platelet levels on admission and an increasing number of EVD
      placement attempts correlated with an increased risk of hemorrhage on placement.
      Only those with an EVD placed at bedside were more likely to have hemorrhage on
      EVD removal. CONCLUSIONS Multiple studies have reported varying EVD hemorrhage
      rates while very few studies have described hemorrhage secondary to EVD removal.
      This is the first reported analysis of risk factors associated with hemorrhage on
      EVD removal. Hemorrhages occur relatively frequently following EVD placement and
      removal, though clinical significance of these events seems to be low.

PMID- 27035169
TI  - Meta-analysis and systematic review of risk factors for shunt dependency after
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by
      hydrocephalus in 6.5%-67% of cases. Some patients with aSAH develop shunt
      dependency, which is often managed by ventriculoperitoneal shunt placement. The
      objectives of this study were to review published risk factors for shunt
      dependency in patients with aSAH, determine the level of evidence for each
      factor, and calculate the magnitude of each risk factor to better guide patient
      management. METHODS The authors searched PubMed and MEDLINE databases for Level A
      and Level B articles published through December 31, 2014, that describe factors
      affecting shunt dependency after aSAH and performed a systematic review and meta
      analysis, stratifying the existing data according to level of evidence. RESULTS
      On the basis of the results of the meta-analysis, risk factors for shunt
      dependency included high Fisher grade (OR 7.74, 95% CI 4.47-13.41), acute
      hydrocephalus (OR 5.67, 95% CI 3.96-8.12), in-hospital complications (OR 4.91,
      95% CI 2.79-8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80
      5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51-4.21), rehemorrhage
      (OR 2.21, 95% CI 1.24-3.95), posterior circulation location of the aneurysm (OR
      1.85, 95% CI 1.35-2.53), and age >= 60 years (OR 1.81, 95% CI 1.50-2.19). The
      only risk factor included in the meta-analysis that did not reach statistical
      significance was female sex (OR 1.13, 95% CI 0.77-1.65). CONCLUSIONS The authors
      identified several risk factors for shunt dependency in aSAH patients that help
      predict which patients are likely to require a permanent shunt. Although some of
      these risk factors are not independent of each other, this information assists
      clinicians in identifying at-risk patients and managing their treatment.

PMID- 27035170
TI  - Clinical characteristics of arteriovenous malformations in the cerebellopontine
      angle cistern.
AB  - OBJECTIVE Arteriovenous malformations (AVMs) in the cerebellopontine angle
      cistern (CPAC) are specific lesions that can cause neurovascular compression
      syndromes as well as intracranial hemorrhage. Although case reports describing
      the CPAC AVMs, especially those presenting with trigeminal neuralgia (TN), have
      been accumulating by degrees, the pathophysiology of CPAC AVMs remains obscure.
      The authors' purpose in the present study was to evaluate the clinical and
      radiographic features of CPAC AVMs as well as the treatment options. METHODS This
      study defined a CPAC AVM as a small AVM predominantly located in the CPAC with
      minimal extension into the pial surface of the brainstem and closely associated
      with cranial nerves. All patients with CPAC AVMs treated in the authors'
      affiliated hospitals over a 16-year period were retrospectively identified.
      Clinical charts, imaging studies, and treatment options were evaluated. RESULTS
      Ten patients (6 men and 4 women), ranging in age from 56 to 77 years (mean 65.6
      years), were diagnosed with CPAC AVMs according to the authors' definition. Six
      patients presented with hemorrhage, 3 with TN, and the remaining patient
      developed a hemorrhage subsequent to TN. Seven AVMs were associated with the
      trigeminal nerve (Group V), and 3 with the facial-vestibulocochlear nerve complex
      (Group VII-VIII). All patients in Group VII-VIII presented with the hemorrhage
      instead of hemifacial spasm. Regarding angioarchitecture, the intrinsic pontine
      arteries provided the blood supply for all CPAC AVMs in Group V. In addition, 5
      of 7 AVMs with hemorrhagic episodes accompanied flow-related aneurysms, although
      no aneurysm was detected in patients with TN alone. With respect to treatment,
      all patients with hemorrhagic presentation underwent Gamma Knife surgery (GKS),
      resulting in favorable outcomes except for 1 patient who experienced rebleeding
      after GKS, which was caused by the repeated rupture of a feeder aneurysm. The
      AVMs causing TN were managed with surgery, GKS, or a combination, according to
      the nidus-nerve relationship. All patients eventually obtained pain relief.
      CONCLUSIONS Clinical symptoms caused by CPAC AVMs occur at an older age compared
      with AVMs in other locations; CPAC AVMs also have distinctive angioarchitectures
      according to their location in the CPAC. Although GKS is likely to be an
      effective treatment option for the CPAC AVMs with hemorrhagic presentations, it
      seems ideal to obliterate the flow-related aneurysms before performing GKS,
      although this is frequently challenging. For CPAC AVMs with TN, it is important
      to evaluate the nidus-nerve relationship before treatment, and GKS is especially
      useful for patients who do not require urgent pain relief.

PMID- 27035171
TI  - The role of alternative anastomosis sites in occipital artery-posterior inferior
      cerebellar artery bypass in the absence of the caudal loop using the far-lateral
      approach.
AB  - OBJECTIVE Occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass
      is a technically challenging procedure for posterior fossa revascularization. The
      caudal loop of the PICA is considered the optimal site for OA-PICA anastomosis,
      however its absence can increase the technical difficulty associated with this
      procedure. The use of the far-lateral approach for accessing alternative
      anastomosis sites in OA-PICA bypass in patients with absent or unavailable caudal
      loops of PICA is evaluated. METHODS A morphometric analysis of OA-PICA bypass
      with anastomosis on each segment of the PICA was performed on 5 cadaveric
      specimens through the conventional midline foramen magnum and far-lateral
      approaches. The difficulty level associated with anastomoses at each segment was
      qualitatively assessed in each approach for exposure and maneuverability by
      multiple surgeons. A series of 8 patients who underwent OA-PICA bypass for
      hemodynamic ischemia or ruptured dissecting posterior fossa aneurysms are
      additionally reviewed and described, and the clinical significance of the caudal
      loop of PICA is discussed. RESULTS Anastomosis on the caudal loop could be
      performed more superficially than on any other segment (p < 0.001). A far-lateral
      approach up to the medial border of the posterior condylar canal provided a 13.5
      +/- 2.2-mm wider corridor than the conventional midline foramen magnum approach,
      facilitating access to alternative anastomosis sites. The far-lateral approach
      was successfully used for OA-PICA bypass in 3 clinical cases whose caudal loops
      were absent, whereas the midline foramen magnum approach provided sufficient
      exposure for caudal loop bypass in the remaining 5 cases. CONCLUSIONS The absence
      of the caudal loop of the PICA is a major contributing factor to the technical
      difficulty of OA-PICA bypass. The far-lateral approach is a useful surgical
      option for OA-PICA bypass when the caudal loop of the PICA is unavailable.

PMID- 27035172
TI  - Masseteric-facial nerve neurorrhaphy: results of a case series.
AB  - OBJECTIVE Facial palsy is a well-known functional and esthetic problem that
      bothers most patients and affects their social relationships. When the time
      between the onset of paralysis and patient presentation is less than 18 months
      and the proximal stump of the injured facial nerve is not available, another
      nerve must be anastomosed to the facial nerve to reactivate its function. The
      masseteric nerve has recently gained popularity over the classic hypoglossus
      nerve as a new motor source because of its lower associated morbidity rate and
      the relative ease with which the patient can activate it. The aim of this work
      was to evaluate the effectiveness of masseteric-facial nerve neurorrhaphy for
      early facial reanimation. METHODS Thirty-four consecutive patients (21 females,
      13 males) with early unilateral facial paralysis underwent masseteric-facial
      nerve neurorrhaphy in which an interpositional nerve graft of the great auricular
      or sural nerve was placed. The time between the onset of paralysis and surgery
      ranged from 2 to 18 months (mean 13.3 months). Electromyography revealed mimetic
      muscle fibrillations in all the patients. Before surgery, all patients had House
      Brackmann Grade VI facial nerve dysfunction. Twelve months after the onset of
      postoperative facial nerve reactivation, each patient underwent a clinical
      examination using the modified House-Brackmann grading scale as a guide. RESULTS
      Overall, 91.2% of the patients experienced facial nerve function reactivation.
      Facial recovery began within 2-12 months (mean 6.3 months) with the restoration
      of facial symmetry at rest. According to the modified House-Brackmann grading
      scale, 5.9% of the patients had Grade I function, 61.8% Grade II, 20.6% Grade
      III, 2.9% Grade V, and 8.8% Grade VI. The morbidity rate was low; none of the
      patients could feel the loss of masseteric nerve function. There were only a few
      complications, including 1 case of postoperative bleeding (2.9%) and 2 local
      infections (5.9%), and a few patients complained about partial loss of
      sensitivity of the earlobe or a small area of the ankle and foot, depending on
      whether great auricular or sural nerves were harvested. CONCLUSIONS The surgical
      technique described here seems to be efficient for the early treatment of facial
      paralysis and results in very little morbidity.

PMID- 27035173
TI  - Endoscopic transsphenoidal anterior petrosal approach for locally aggressive
      tumors involving the internal auditory canal, jugular fossa, and cavernous sinus.
AB  - OBJECTIVE Reports about endoscopic endonasal surgery for skull base tumors
      involving the lateral part of petrous apex remain scarce. The authors present
      their experience with the endoscopic transsphenoidal anterior petrosal (ETAP)
      approach through the retrocarotid space for tumors involving the internal
      auditory canal, jugular fossa, and cavernous sinus. METHODS The authors performed
      the ETAP approach in 10 patients with 11 tumors (bilateral in 1 patient) that
      extensively occupied the lateral part of petrous apex, e.g., the internal
      auditory canal and jugular fossa. Eight patients presented with diplopia
      (unilateral abducens nerve palsy), 3 with tinnitus, and 1 with unilateral hearing
      loss with facial palsy. After wide anterior sphenoidotomy, the sellar floor,
      clival recess, and carotid prominence were verified. Tumors were approached via
      an anteromedial petrosectomy through the retrocarotid triangular space, defined
      by the cavernous and vertical segments of the internal carotid artery (ICA), the
      clivus, and the petrooccipital fissure. The surgical window was easily enlarged
      by drilling the petrous bone along the petrooccipital fissure. After exposure of
      the tumor and ICA, dissection and resection of the tumor were mainly performed
      under direct visualization with 30 degrees  and 70 degrees  endoscopes. RESULTS
      Gross-total resection was achieved in 8 patients (9 tumors). In a patient with
      invasive meningioma, the tumor was strongly adherent to the ICA, necessitating
      partial resection. Postoperatively, all 8 patients who had presented with
      abducens nerve palsy preoperatively showed improvement within 6 months. In the
      patient presenting with hearing loss and facial palsy, the facial palsy
      completely resolved within 3 months, but hearing loss remained. Regarding
      complications, 3 patients showed mild and transient abducens nerve palsy
      resolving within 2 weeks, 3 months, and 6 months. Postoperative CSF rhinorrhea
      requiring surgical repair was observed in 1 patient. No patient exhibited hearing
      deterioration, facial palsy, or symptoms of lower cranial nerve palsy after
      surgery. CONCLUSIONS The ETAP approach can offer a simple, less invasive option
      for invasive skull base tumors involving petrous regions, including the internal
      auditory canal, jugular fossa, and cavernous sinus. The ETAP approach can reach
      more extensive areas in the extradural regions around the petrous bone. The
      authors' results indicate that the transsphenoidal retrocarotid route is
      sufficient to approach the petrosal areas in select cases. Further expansion of
      the surgical field is not always necessary. However, experience with intradural
      lesions remains limited, and the extent of tumor resection largely depends on
      tumor characteristics. Application of the ETAP approach should thus be carefully
      determined in each patient, taking into consideration the size of the
      retrocarotid window and tumor characteristics.

PMID- 27035174
TI  - A matched cohort comparison of clinical outcomes following microsurgical
      resection or stereotactic radiosurgery for patients with small- and medium-sized
      vestibular schwannomas.
AB  - OBJECTIVE A randomized trial that compares clinical outcomes following
      microsurgery (MS) or stereotactic radiosurgery (SRS) for patients with small- and
      medium-sized vestibular schwannomas (VSs) is impractical, but would have
      important implications for clinical decision making. A matched cohort analysis
      was conducted to evaluate clinical outcomes in patients treated with MS or SRS.
      METHODS The records of 399 VS patients who were cared for by 2 neurosurgeons and
      1 neurotologist between 2001 and 2014 were evaluated. From this data set, 3
      retrospective matched cohorts were created to compare hearing preservation (21
      matched pairs), facial nerve preservation (83 matched pairs), intervention-free
      survival, and complication rates (85 matched pairs) between cases managed with
      SRS and patients managed with MS. Cases were matched for age at surgery (+/- 10
      years) and lesion size (+/- 0.1 cm). To compare hearing outcomes, cases were
      additionally matched for preoperative Class A hearing according to the American
      Academy of Otolaryngology-Head and Neck Surgery guidelines. To compare facial
      nerve (i.e., cranial nerve [CN] VII) outcomes, cases were additionally matched
      for preoperative House-Brackmann (HB) score. Investigators who were not involved
      with patient care reviewed the clinical and imaging records. The reported
      outcomes were as assessed at the time of the last follow-up, unless otherwise
      stated. RESULTS The preservation of preoperative Class A hearing status was
      achieved in 14.3% of MS cases compared with 42.9% of SRS cases (OR 4.5; p < 0.05)
      after an average follow-up interval of 43.7 months and 30.3 months, respectively.
      Serviceable hearing was preserved in 42.8% of MS cases compared with 85.7% of SRS
      cases (OR 8.0; p < 0.01). The rates of postoperative CN VII dysfunction were low
      for both groups, although significantly higher in the MS group (HB III-IV 11% vs
      0% for SRS; OR 21.3; p < 0.01) at a median follow-up interval of 35.7 and 19.0
      months for MS and SRS, respectively. There was no difference in the need for
      subsequent intervention (2 MS patients and 2 SRS patients). CONCLUSIONS At this
      high-volume center, VS resection or radiosurgery for tumors <= 2.8 cm in diameter
      was associated with low overall morbidity. The need for subsequent intervention
      was the same in both groups. SRS was associated with improved hearing and facial
      preservation rates and reduced morbidity, but with a shorter average follow-up
      period. Facial function was excellent in both groups. Since patients were not
      randomly selected for surgery, different clinical outcomes may be of different
      value to individual patients. Both anticipated medical outcomes and patient goals
      remain the drivers of treatment decisions.

PMID- 27035175
TI  - Prediction of outcome after subarachnoid hemorrhage: timing of clinical
      assessment.
AB  - OBJECTIVE Currently, early prediction of outcome after spontaneous subarachnoid
      hemorrhage (SAH) lacks accuracy despite multiple studies addressing this issue.
      The clinical condition of the patient on admission as assessed using the World
      Federation of Neurosurgical Societies (WFNS) grading scale is currently
      considered the gold standard. However, the timing of the clinical assessment is
      subject to debate, as is the contribution of additional predictors. The aim of
      this study was to identify either the conventional WFNS grade on admission or the
      WFNS grade after neurological resuscitation (rWFNS) as the most accurate
      predictor of outcome after SAH. METHODS This prospective observational cohort
      study included 1620 consecutive patients with SAH admitted between January 1998
      and December 2014 at our university neurovascular center. The primary outcome
      measure was a poor modified Rankin Scale score at the 2-month follow-up. Clinical
      predictors were identified using multivariate logistic regression analyses. Area
      under the receiver operating characteristic curve (AUC) analysis was used to test
      discriminative performance of the final model. An AUC of > 0.8 was regarded as
      indicative of a model with good prognostic value. RESULTS Poor outcome (modified
      Rankin Scale Score 4-6) was observed in 25% of the patients. The rWFNS grade was
      a significantly stronger predictor of outcome than the admission WFNS grade. The
      rWFNS grade was significantly associated with poor outcome (p < 0.001) as well as
      increasing age (p < 0.001), higher modified Fisher grade (p < 0.001), larger
      aneurysm size (p < 0.001), and the presence of an intracerebral hematoma (OR 1.8,
      95% CI 1.2-2.8; p = 0.002). The final model had an AUC of 0.87 (95% CI 0.85
      0.89), which indicates excellent prognostic value regarding the discrimination
      between poor and good outcome after SAH. CONCLUSIONS In clinical practice and
      future research, neurological assessment and grading of patients should be
      performed using the rWFNS to obtain the best representation of their clinical
      condition.

PMID- 27035176
TI  - Avoidance of ischemic complications after resection of a brain lesion based on
      intraoperative real-time recognition of the vasculature using laser speckle flow
      imaging.
AB  - OBJECTIVE To avoid ischemic complications, it is important to consider the
      arteries in resection planning for lesions such as a vascular intraparenchymal
      tumor and arteriovenous malformation. Here, the clinical application of laser
      speckle flow imaging (LSFI) as a complementary method for the management of mass
      lesion-related arteries during surgery was evaluated. METHODS LSFI was performed
      in 12 patients with mass lesion-related arteries and brain tumor or arteriovenous
      malformation. The portable LSFI device was centered over the surgical field, and
      the relative cerebral blood flow (CBF) before and after the temporary
      interruption of the arteries was measured through continuous recording. CBF
      fluctuations permitted the classification of 3 kinds of artery-a feeding artery
      (FA), a "passing through" artery (PA), and a combined FA and PA (FA+PA)-based on
      decreased relative CBF in the inner resection area and unchanged CBF in the
      surrounding area (FA), unchanged CBF in the inner area and decreased CBF in the
      surrounding area (PA), or decreased CBF in both areas (FA+PA). This information
      allowed the appropriate management of these arteries and avoidance of
      postoperative ischemic complications. RESULTS Good visualization of CBF in the
      surgical field and relative CBF measurements in the regions of interest were
      achieved in real time with excellent spatiotemporal resolution. In 11 patients
      (92%) and 20 regions of interest, a decline in CBF was observed after temporary
      interruption of the FA (n = 8), PA (n = 2), and FA+PA (n = 2) types. There was a
      significant average reduction in CBF of 15.3% +/- 29.0%. There were no ischemic
      complications, and only 1 patient had a postoperative ischemic lesion caused by
      resection through an artery that could not be viewed by LSFI due to a positional
      problem. CONCLUSIONS LSFI permits noninvasive and rapid intraoperative real-time
      recognition of mass lesion-related vasculature. This information can be used to
      avoid ischemic complications as a procedure complementary to neurophysiological
      monitoring.

PMID- 27035177
TI  - Impact of Glasgow Coma Scale score and pupil parameters on mortality rate and
      outcome in pediatric and adult severe traumatic brain injury: a retrospective,
      multicenter cohort study.
AB  - OBJECTIVE Prediction of death and functional outcome is essential for determining
      treatment strategies and allocation of resources for patients with severe
      traumatic brain injury (TBI). The aim of this study was to evaluate, by using
      pupillary status and Glasgow Coma Scale (GCS) score, if patients with severe TBI
      who are <= 15 years old have a lower mortality rate and better outcome than
      adults with severe TBI. METHODS A retrospective cohort analysis of patients
      suffering from severe TBI registered in the Trauma Registry of the German Society
      for Trauma Surgery between 2002 and 2013 was undertaken. Severe TBI was defined
      as an Abbreviated Injury Scale of the head (AIShead) score of >= 3 and an AIS
      score for any other part of the body that does not exceed the AIShead score. Only
      patients with complete data (GCS score, age, and pupil parameters) were included.
      To assess the impact of GCS score and pupil parameters, the authors also used the
      recently introduced Eppendorf-Cologne Scale and divided the study population into
      2 groups: children (0-15 years old) and adults (16-55 years old). Each patient's
      outcome was measured at discharge from the trauma center by using the Glasgow
      Outcome Scale. RESULTS A total of 9959 patients fulfilled the study inclusion
      criteria; 888 (8.9%) patients were <= 15 years old (median 10 years). The overall
      mortality rate and the mortality rate for patients with a GCS of 3 and
      bilaterally fixed and dilated pupils (19.9% and 16.3%, respectively) were higher
      for the adults than for the pediatric patients (85% vs 80.9%, respectively),
      although cardiopulmonary resuscitation rates were significantly higher in the
      pediatric patients (5.6% vs 8.8%, respectively). In the multivariate logistic
      regression analysis, no motor response (OR 3.490, 95% CI 2.240-5.435) and fixed
      pupils (OR 4.197, 95% CI 3.271-5.386) and bilateral dilated pupils (OR 2.848, 95%
      CI 2.282-3.556) were associated with a higher mortality rate. Patients <= 15
      years old had a statistically lower mortality rate (OR 0.536, 95% CI 0.421-0.814;
      p = 0.001). The rate of good functional outcomes (Glasgow Outcome Scale Score 4
      or 5) was higher in pediatric patients than in the adults (72.2% vs 63.1%,
      respectively). CONCLUSIONS This study found that severe TBI in children aged <=
      15 years is associated with a lower mortality rate and superior functional
      outcome than in adults. Also, children admitted with a missing motor response or
      fixed and bilaterally dilated pupils also have a lower mortality rate and higher
      functional outcome than adults with the same initial presentation. Therefore,
      patients suffering from severe TBI, especially pediatric patients, could benefit
      from early and aggressive treatment.

PMID- 27035178
TI  - Anterior spinal and bulbar artery supply to the posterior inferior cerebellar
      artery revealed by a ruptured aneurysm: case report.
AB  - The posterior inferior cerebellar artery (PICA) is a vessel located between the
      intra- and extracranial circulation. The artery is characterized by a complex
      embryological development and numerous anatomical variants. The authors present a
      case of the PICA supplied by both a hypertrophic anterior spinal artery and a
      hypoplastic bulbar artery. This unusual arrangement somehow completes the list of
      previously published variants, and the spontaneous rupture of a related aneurysm
      confirmed the fragility of this network. The authors discuss anatomical and
      treatment considerations.

PMID- 27035179
TI  - Interobserver Reproducibility of the PI-RADS Version 2 Lexicon: A Multicenter
      Study of Six Experienced Prostate Radiologists.
AB  - Purpose To determine the interobserver reproducibility of the Prostate Imaging
      Reporting and Data System (PI-RADS) version 2 lexicon. Materials and Methods This
      retrospective HIPAA-compliant study was institutional review board-approved. Six
      radiologists from six separate institutions, all experienced in prostate magnetic
      resonance (MR) imaging, assessed prostate MR imaging examinations performed at a
      single center by using the PI-RADS lexicon. Readers were provided screen captures
      that denoted the location of one specific lesion per case. Analysis entailed two
      sessions (40 and 80 examinations per session) and an intersession training period
      for individualized feedback and group discussion. Percent agreement (fraction of
      pairwise reader combinations with concordant readings) was compared between
      sessions. kappa coefficients were computed. Results No substantial difference in
      interobserver agreement was observed between sessions, and the sessions were
      subsequently pooled. Agreement for PI-RADS score of 4 or greater was 0.593 in
      peripheral zone (PZ) and 0.509 in transition zone (TZ). In PZ, reproducibility
      was moderate to substantial for features related to diffusion-weighted imaging
      (kappa = 0.535-0.619); fair to moderate for features related to dynamic contrast
      material-enhanced (DCE) imaging (kappa = 0.266-0.439); and fair for definite
      extraprostatic extension on T2-weighted images (kappa = 0.289). In TZ,
      reproducibility for features related to lesion texture and margins on T2-weighted
      images ranged from 0.136 (moderately hypointense) to 0.529 (encapsulation). Among
      63 lesions that underwent targeted biopsy, classification as PI-RADS score of 4
      or greater by a majority of readers yielded tumor with a Gleason score of 3+4 or
      greater in 45.9% (17 of 37), without missing any tumor with a Gleason score of
      3+4 or greater. Conclusion Experienced radiologists achieved moderate
      reproducibility for PI-RADS version 2, and neither required nor benefitted from a
      training session. Agreement tended to be better in PZ than TZ, although was weak
      for DCE in PZ. The findings may help guide future PI-RADS lexicon updates. ((c))
      RSNA, 2016 Online supplemental material is available for this article. 

PMID- 27035208
TI  - PageRank analysis reveals topologically expressed genes correspond to psoriasis
      and their functions are associated with apoptosis resistance.
AB  - Psoriasis is an inflammatory skin disease. Deceleration in keratinocyte apoptosis
      is the most significant pathological change observed in psoriasis. To detect a
      meaningful correlation between the genes and gene functions associated with the
      mechanism underlying psoriasis, 927 differentially expressed genes (DEGs) were
      identified using the Gene Expression Omnibus database, GSE13355 [false discovery
      rate (FDR) <0.01; |log fold change >1] with the package in R langue. The selected
      DEGs were further constructed using the search tool for the retrieval of
      interacting genes, in order to analyze the interaction network between the DEGs.
      Subsequent to PageRank analysis, 14 topological hub genes were identified, and
      the functions and pathways in the hub genes network were analyzed. The top-ranked
      hub gene, estrogen receptor-1 (ESR1) is downregulated in psoriasis, exhibited
      binding sites enriched with genes possessing anti-apoptotic functions. The ESR1
      gene encodes estrogen receptor alpha (ERalpha); a reduced level of ERalpha
      expression provides a crucial foundation in response to the anti-apoptotic
      activity of psoriatic keratinocytes by activating the expression of anti
      apoptotic genes. Furthermore, it was detected that the pathway that is associated
      most significantly with psoriasis is the pathways in cancer. Pathways in cancer
      may protect psoriatic cells from apoptosis by inhibition of ESR1 expression. The
      present study provides support towards the investigation of ESR1 gene function
      and elucidates that the interaction with anti-apoptotic genes is involved in the
      underlying biological mechanisms of resistance to apoptosis in psoriasis.
      However, further investigation is required to confirm the present results. 

PMID- 27035210
TI  - Photodissociation of Cerium Oxide Nanocluster Cations.
AB  - Cerium oxide cluster cations, CexOy(+), are produced via laser vaporization in a
      pulsed nozzle source and detected with time-of-flight mass spectrometry. The mass
      spectrum displays a strongly preferred oxide stoichiometry for each cluster with
      a specific number of metal atoms x, with x <= y. Specifically, the most prominent
      clusters correspond to the formula CeO(CeO2)n(+). The cluster cations are mass
      selected and photodissociated with a Nd:YAG laser at either 532 or 355 nm. The
      prominent clusters dissociate to produce smaller species also having a similar
      CeO(CeO2)n(+) formula, always with apparent leaving groups of (CeO2). The
      production of CeO(CeO2)n(+) from the dissociation of many cluster sizes
      establishes the relative stability of these clusters. Furthermore, the consistent
      loss of neutral CeO2 shows that the smallest neutral clusters adopt the same
      oxidation state (IV) as the most common form of bulk cerium oxide. Clusters with
      higher oxygen content than the CeO(CeO2)n(+) masses are present with much lower
      abundance. These species dissociate by the loss of O2, leaving surviving clusters
      with the CeO(CeO2)n(+) formula. Density functional theory calculations on these
      clusters suggest structures composed of stable CeO(CeO2)n(+) cores with excess
      oxygen bound to the surface as a superoxide unit (O2(-)). 

PMID- 27035209
TI  - DNA methylation as a potential mediator of environmental risks in the development
      of childhood acute lymphoblastic leukemia.
AB  - 5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen
      to approximately 90%, yet the causal disease pathway is still poorly understood.
      Evidence suggests multiple 'hits' are required for disease progression; an
      initial genetic abnormality followed by additional secondary 'hits'. It is
      plausible that environmental influences may trigger these secondary hits, and
      with the peak incidence of diagnosis between 2 and 5 years of age, early life
      exposures are likely to be key. DNA methylation can be modified by many
      environmental exposures and is dramatically altered in cancers, including
      childhood ALL. Here we explore the potential that DNA methylation may be involved
      in the causal pathway toward disease by acting as a mediator between established
      environmental factors and childhood ALL development. 

PMID- 27035211
TI  - Reshaping, Fragmentation, and Assembly of Gold Nanoparticles Assisted by Pulse
      Lasers.
AB  - The vast majority of the outstanding applications of metal nanoparticles (NPs)
      developed during the last two decades have arisen from their unique optical
      properties. Within this context, rational synthesis and assembly of gold NPs have
      been the main research focus, aiming at the design of nanoplasmonic devices with
      tailored optical functionalities. The progress made in this field is thus to be
      ascribed to the understanding of the origin of the interaction between light and
      such gold nanostructures, the dynamics of which have been thoroughly investigated
      with significant contributions from short and ultrashort pulse laser
      technologies. We focus this Account on the potential of pulse lasers to provide
      new fundamental insights into the electron dynamics involved in the interaction
      of light with the free conduction electrons of Au NPs, that is, localized surface
      plasmon resonances (LSPRs). The excitation of LSPRs with a femtosecond pulse
      laser is followed by thermalization of the Au NP electrons and the subsequent
      relaxation of the nanocrystal lattice and the surrounding environment, which
      generally results in surface melting. By contrast, nanosecond irradiation usually
      induces AuNP fragmentation and uncontrolled melting due to overlapping excitation
      and relaxation phenomena. These concepts have been exploited toward the
      preparation of highly monodisperse gold nanospheres via pulse laser irradiation
      of polyhedral nanocrystal colloids, or in the fabrication of nanostructures with
      "written-in" optical properties. The applicability of pulsed coherent light has
      been extended toward the direct synthesis and manipulation of Au NPs. Through
      ablation of a gold target in a liquid with pulse lasers, spherical Au NPs can be
      synthesized with no need of stabilizing ligands, which is a great advantage in
      terms of reducing toxicity, rendering these NPs particularly suitable for medical
      applications. In addition, femtosecond laser irradiation has been proven a unique
      tool for the controlled welding of plasmonic gold nanostructures by
      electromagnetic field enhancement at the hot spots of assembled Au NPs. The
      combination of such nanostructures with pulse lasers promises significant
      chemical and biochemical advances, including the structural determination of
      organic reaction intermediates, the investigation of phase transitions in
      inorganic nanomaterials at mild reaction conditions, or the efficient
      photothermal destruction of cancer cells avoiding damage of surrounding tissue. 

PMID- 27035212
TI  - Differentiating Metastatic and Non-metastatic Tumor Cells from Their
      Translocation Profile through Solid-State Micropores.
AB  - Cancer treatment, care, and outcomes are much more effective if started at early
      stages of the disease. The presence of malignant cancer cells in human samples
      such as blood or biopsied tissue can be used to reduce overtreatment and
      underdiagnosis as well as for prognosis monitoring. Reliable quantification of
      metastatic tumor cells (MTCs) and non-metastatic tumor cells (NMTCs) from human
      samples can help in cancer staging as well. We report a simple, fast, and
      reliable approach to identify and quantify metastatic and non-metastatic cancer
      cells from whole biological samples in a point-of-care manner. The metastatic
      (MDA MB-231) and non-metastatic (MCF7) breast cancer cells were pushed through a
      solid-state micropore made in a 200 nm thin SiO2 membrane while measuring current
      across the micropore. The cells generated very distinctive translocation
      profiles. The translocation differences stemmed from their peculiar
      mechanophysical properties. The detection efficiency of the device for each type
      of tumor cells was ~75%. MTCs showed faster translocation (36%) and 34% less pore
      blockage than NMTCs. The micropore approach is simple, exact, and quantitative
      for metastatic cell detection in a lab-on-a chip setting, without the need for
      any preprocessing of the sample.

PMID- 27035213
TI  - Polysiloxane Functionalized Carbon Dots and Their Cross-Linked Flexible Silicone
      Rubbers for Color Conversion and Encapsulation of White LEDs.
AB  - In this work, aminopropylmethylpolysiloxane (AMS) functionalized luminescent
      carbon dots (AMS-CDs) were prepared via a one-step solvothermal method. AMS-CDs
      could be self- or co-cross-linking with AMS to form 3D flexible transparent
      silicone rubbers (SRs) where CDs acted as cross-linking points, so the loading
      fraction of AMS-CDs could be adjusted from 10 to 100 wt %, thus modulating
      fluorescence properties and flexibility of silicone rubbers. Because of the self
      curing property and high thermal stability, AMS-CDs were also studied in white
      LEDs (WLEDs), serving as a color conversion and encapsulation layer of GaN based
      blue LEDs simultaneously that would avoid the traditional problem of poor
      compatibility between emitting and packaging materials. And the color coordinate
      of AMS-CDs based WLEDs (0.33, 0.28) was very close to the pure white light. In
      addition, the obtained CDs cross-linked SRs had good transparency (T > 80%) at
      510-1400 nm and high refractive indexes (1.33-1.54) that could meet the need of
      commercial packaging materials and optical application. AMS-CDs were also
      promising to be used in the UV LEDs based WLEDs according to their wide
      wavelength emission and flexible optoelectronic device. 

PMID- 27035214
TI  - Challenges in the Structure Determination of Self-Assembled Metallacages: What Do
      Cage Cavities Contain, Internal Vapor Bubbles or Solvent and/or Counterions?
AB  - Proving the structures of charged metallacages obtained by metal ion coordination
      driven solution self-assembly is challenging, and the common use of routine NMR
      spectroscopy and mass spectrometry is unreliable. Carefully determined diffusion
      coefficients from diffusion-ordered proton magnetic resonance (DOSY NMR) for six
      cages of widely differing sizes lead us to propose a structural reassignment of
      two molecular cages from a previously favored trimer to a pentamer or hexamer,
      and another from a trimer to a much higher oligomer, possibly an intriguing
      tetradecamer. In the former case, strong support for the reassignment to a larger
      cage is provided by an observation of a slow reversible transformation of the
      initially formed cage into a smaller but spectrally very similar one upon
      dilution. In the latter case, freeze-fracture transmission electron micrographs
      demonstrate that at least some of the solutions are colloidal, and high
      resolution electron transmission and atomic force microscopy images are
      compatible with a tetradecamer but not a trimer. Comparison of solute partial
      molar volumes deduced from measurement of solution density with volumes
      anticipated from molecular models argues strongly against the presence of large
      voids (solvent vapor bubbles) in cages dissolved in nitromethane. The presence of
      bubbles was previously proposed in an attempt to account for the bilinear nature
      of the Eyring plot of the rate constant for pyridine ligand edge exchange
      reaction in one of the cages and for the unusual activation parameters in the
      high-temperature regime. An alternative interpretation is proposed now.

PMID- 27035215
TI  - Controlled Reduction of Tertiary Amides to the Corresponding Alcohols, Aldehydes,
      or Amines Using Dialkylboranes and Aminoborohydride Reagents.
AB  - Dialkylboranes and aminoborohydrides are mild, selective reducing agents
      complementary to the commonly utilized amide reducing agents, such as lithium
      aluminum hydride (LiAlH4) and diisobutylaluminum hydride (DIBAL) reagents.
      Tertiary amides were reduced using 1 or 2 equiv of various dialkylboranes. The
      reduction of tertiary amides required 2 equiv of 9-borabicyclo[3.3.1]nonane (9
      BBN) for complete reduction to give the corresponding tertiary amines. One
      equivalent of sterically hindered disiamylborane reacts with tertiary amides to
      afford the corresponding aldehydes. Aminoborohydrides are powerful and selective
      reducing agents for the reduction of tertiary amides. Lithium
      dimethylaminoborohydride and lithium diisopropylaminoborohydride are prepared
      from n-butyllithium and the corresponding amine-borane. Chloromagnesium
      dimethylaminoborohydride (ClMg(+)[H3B-NMe2](-), MgAB) is prepared by the reaction
      of dimethylamine-borane with methylmagnesium chloride. Solutions of
      aminoborohydride reduce aliphatic, aromatic, and heteroaromatic tertiary amides
      to give the corresponding alcohol, amine, or aldehyde depending on the steric
      requirement of the tertiary amide and the aminoborohydride used.

PMID- 27035216
TI  - MicroRNA-130a promotes the metastasis and epithelial-mesenchymal transition of
      osteosarcoma by targeting PTEN.
AB  - MicroRNAs, which serve as post-transcriptional modulators of numerous genes, have
      been found to be important regulators during the pathogenesis of osteosarcoma.
      This study demonstrates for the first time that microRNA-130a (miR-130a) is
      significantly upregulated in osteosarcoma, and associated with the metastasis of
      osteosarcoma. Elevated level of miR-130a was closely correlated with poor
      clinical features and prognosis of osteosarcoma patients. In vitro assays
      revealed that miR-130a could potentiate the migration, invasion and the
      epithelial-mesenchymal transtion (EMT) of osteosarcoma cells. Moreover,
      phosphatase and tensin homolog (PTEN) was confirmed as not only a direct
      downstream target but also a functional mediator of miR-130a. MiR-130a exerted
      promoting effects on metastatic behavior and EMT of osteosarcoma cells through
      suppressing PTEN expression. Based on these findings, we conclude that miR-130a
      is a promising prognostic biomarker for osteosarcoma patients, and targeting miR
      130a may be a potential treatment option for osteosarcoma patients with
      metastasis. 

PMID- 27035217
TI  - Selective Gas Capture Ability of Gas-Adsorbent-Incorporated Cellulose Nanofiber
      Films.
AB  - The 2,2,6,6-tetramethylpiperidine-1-oxyl radical-oxidized cellulose nanofibers
      (TOCNF) were hybridized with cation and anion-exchange organoclays, where
      poly(amido amine) dendrimers were loaded to enhance the functionality of gas
      adsorption, since dendrimers have the high adsorbability and the enough
      selectivity on the gas adsorption. The thin films were prepared from the
      organoclay-TOCNF hybrids and supplied to the gas adsorption. The adsorption of
      CO2 and NH3 gases increased with an increasing amount of organoclays in TOCNF
      films, but the behavior of the increase depended on gases, clays, and dendrimers.
      The hydrotalcite organoclay-TOCNF films displayed the highest adsorption of both
      gases, but the desorption of CO2 gas from hydrotalcite organoclay-TOCNF films was
      drastically high in comparison with the other systems. While the CO2 gas is
      adsorbed and remained on cationic dendrimer sites in cation-exchange organoclay
      TOCNF films, the CO2 gas is adsorbed on cationic clay sites in anion exchange
      organoclay-TOCNF films, and it is easily desorbed from the films. The NH3
      adsorption is inversive to the CO2 adsorption. Then the CO2 molecules adsorbed on
      the cationic dendrimers and the NH3 molecules adsorbed on the anionic dendrimers
      are preferably captured in these adsorbents. The present research incorporated
      dendrimers will be contributing to the development of gas-specialized adsorbents,
      which are selectively storable only in particular gases.

PMID- 27035218
TI  - Noncyanogenic Cyanoglucoside Cyclooxygenase Inhibitors from Simmondsia chinensis.
AB  - Two new noncyanogenic cyanoglucoside dimers, simmonosides A and B (1 and 2), were
      identified from the aqueous extract of jojoba (Simmondsia chinensis) leaves.
      Compounds 1 and 2 are the first examples of noncyanogenic cyanoglucoside dimers
      containing a unique four-membered ring, representing novel dimerization patterns
      at alpha,beta-unsaturated carbons of a nitrile group in 1 and gamma,delta
      unsaturated carbons in 2. Their structures were elucidated based on spectroscopic
      evidence and electronic circular dichroism (ECD) calculations. Compounds 1 and 2
      exhibit promising COX-2 inhibition activity, with IC50 values of 13.5 and 11.4
      MUM, respectively. 

PMID- 27035219
TI  - p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell
      apoptosis in spontaneous resorption of herniated intervertebral discs: An
      experimental study in rats.
AB  - The present study was performed to investigate the role of p38 mitogen-activated
      protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30
      rats. In the non-contained and p38 MAPK inhibition (p38i) groups, two coccygeal
      intervertebral discs (IVDs) were removed and wounded prior to relocation into the
      subcutaneous space of the skin of the back. In the contained group, the cartilage
      endplates maintained their integrity. Furthermore, SB203580 was injected
      intraperitoneally into the p38i group, whereas saline was injected into the other
      two groups. In the non-contained group, the weight of the relocated IVDs
      decreased to a greater extent over time when compared with the contained and p38i
      groups. Phosphorylated p38, tumor necrosis factor-alpha, and interleukin-1beta
      were observed to exhibit higher expression levels in the non-contained group
      compared with the contained and p38i groups, at weeks 1 and 4 post-surgery. The
      expression level of caspase-3 and the densities of apoptotic disc cells were
      significantly higher in the non-contained group compared with the contained and
      p38i groups at 4 weeks post-surgery. In conclusion, p38 MAPK induces apoptosis in
      IVDs, while also accelerating the resorption of the relocated IVDs. Thus, p38
      MAPK may be important in spontaneous resorption of IVDs. 

PMID- 27035220
TI  - Apelin/APJ system: A novel therapeutic target for oxidative stress-related
      inflammatory diseases (Review).
AB  - Apelin, the endogenous ligand of APJ which is a member of G protein-coupled
      receptors, has been shown to be expressed in a variety of tissues in vivo and to
      exert significant biological effects. Studies have indicated that the apelin/APJ
      system is involved in the regulation of a variety of physiological functions and
      pathological processes, and that it is associated with cardiovascular diseases
      (such as atherosclerosis, hypertension, heart failure and myocardial injury),
      diabetes with microvascular complications, ischemia reperfusion injury, tumors,
      pre-eclampsia, as well as others. The occurrence of these diseases is closely
      related to endothelial dysfunction and the local inflammatory response; however,
      the occurrence of oxidative stress is related to vascular injury, due to the
      excessive generation of reactive oxygen species (ROS) and can lead to vascular
      damage and a series of inflammatory reactions. Therefore, this review summarizes
      the association between apelin/APJ, oxidative stress and inflammation-related
      diseases. In addition, drugs targeting the apelin/APJ system are recommended,
      thus providing a novel therapeutic strategy for oxidative stress-related
      inflammatory diseases.

PMID- 27035221
TI  - Genome-Wide Changes in Peripheral Gene Expression following Sports-Related
      Concussion.
AB  - We conducted a prospective study to identify genome-wide changes in peripheral
      gene expression before and after sports-related concussion (SRC). A total of 253
      collegiate contact athletes underwent collection of peripheral blood mononuclear
      cells (PBMCs) before the sport season (baseline). Sixteen athletes who
      subsequently developed an SRC, along with 16 non-concussed teammate controls,
      underwent repeat collection of PBMCs within 6 h of injury (acutely). Concussed
      athletes underwent additional sample collection at 7 days post-injury (sub
      acutely). Messenger RNA (mRNA) expression at baseline was compared with mRNA
      expression acutely and sub-acutely post-SRC. To estimate the contribution of
      physical exertion to gene changes, baseline samples from athletes who
      subsequently developed an SRC were compared with samples from uninjured teammate
      controls collected at the acute time-point. Clinical outcome was determined by
      changes in post-concussive symptoms, postural stability, and cognition from
      baseline to the sub-acute time-point. SRC athletes had significant changes in
      mRNA expression at both the acute and sub-acute time-points. There were no
      significant expression changes among controls. Acute transcriptional changes
      centered on interleukins 6 and 12, toll-like receptor 4, and NF-kappaB. Sub-acute
      gene expression changes centered on NF-kappaB, follicle stimulating hormone,
      chorionic gonadotropin, and protein kinase catalytic subunit. All SRC athletes
      were clinically back to baseline by Day 7. In conclusion, acute post-SRC
      transcriptional changes reflect regulation of the innate immune response and the
      transition to adaptive immunity. By 7 days, transcriptional activity is centered
      on regulating the hypothalamic-pituitary-adrenal axis. Future efforts to compare
      expressional changes in fully recovered athletes with those who do not recover
      from SRC could suggest putative targets for therapeutic intervention.

PMID- 27035222
TI  - Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in
      human osteosarcoma cell line MG-63 through the ROS/JNK signaling pathway.
AB  - The present study was carried out to investigate the effect and mechanisms of
      aloe-emodin (AE)-mediated photodynamic therapy (AE-PDT) on the human osteosarcoma
      cell line MG-63. After treatment with AE-PDT, the human osteosarcoma cell line MG
      63 was tested for levels of viability, autophagy, reactive oxygen species (ROS)
      and apoptosis and changes in cell morphology with the Cell Counting Kit-8 (CCK
      8), monodansylcadaverine (MDC) and Hoechst staining and transmission electron
      microscopy. The expression of proteins including LC-3, cleaved caspase-3, Beclin
      1, Bcl-2, p-JNK, t-JNK and beta-actin was examined with western blotting. AE-PDT
      significantly inhibited the viability of the MG-63 cells in an AE-concentration-
      and PDT energy density-dependent manner. Autophagy and apoptosis of MG-63 cells
      was substantially promoted in the AE-PDT group compared to the control group, the
      AE alone group and the light emitting diode (LED) alone group. Inhibition of
      autophagy by 3-methyladenine (3-MA) (5 mM) and chloroquine (CQ) (15 uM)
      significantly promoted the apoptosis rate and improved the sensitivity of the MG
      63 cells to AE-PDT. AE-PDT was found to induce the expression of ROS and p-JNK.
      ROS scavenger, N-acetyl-L-cysteine (NAC, 5 mM), was able to hinder the autophagy,
      apoptosis and phosphorylation of JNK, and JNK inhibitor (SP600125, 10 uM)
      significantly inhibited the autophagy and apoptosis, and attenuated the
      sensitivity of MG63 cells to AE-PDT. In conclusion, AE-PDT induced the autophagy
      and apoptosis of human osteosarcoma cell line MG-63 through the activation of the
      ROS-JNK signaling pathway. Autophagy may play a protective role during the early
      stage following treatment of AE-PDT. 

PMID- 27035223
TI  - Chemical chaperone 4-phenylbutyric acid protects H9c2 cardiomyocytes from
      ischemia/reperfusion injury by attenuating endoplasmic reticulum stress-induced
      apoptosis.
AB  - Myocardial ischemia/reperfusion (I/R) is a potential contributor to high rates of
      mortality in several cardiovascular diseases. I/R initiates the unfolded protein
      response and endoplasmic reticulum (ER) stress, which may lead to apoptotic
      pathways and exaggerate I/R injury. 4-phenylbutyric acid (4-PBA), a low molecular
      weight, terminal aromatic substituted fatty acid, has been reported to function
      as an ER chaperone. The aim of the present study was to investigate whether 4-PBA
      is able to reduce ER stress-induced apoptosis and prevent cardiomyocyte damage
      during the process of I/R in vitro. Accordingly, the rat cardiomyocyte line,
      H9c2, was treated with hypoxia/reoxygenation as an I/R model in vitro. Myocardium
      apoptosis was determined with TUNEL staining. The expression of ER stress-related
      proteins were examined by western blotting. The resulting data showed that I/R
      activates the ER stress proteins, glucose-regulated protein 78, activating
      transcription factor 6 and protein kinase RNA-like endoplasmic reticulum kinase,
      which were all reduced by pretreatment with 4-PBA. In addition, pretreatment with
      4-PBA significantly inhibited the expression levels of pro-apoptotic proteins,
      C/EBP homologous protein, B cell lymphoma (Bcl-2)-associated X protein and
      phosphorylated c-Jun N-terminal kinase, and enhanced the expression of the anti
      apoptotic protein Bcl-2 (n=3; P<0.05). The data demonstrated that I/R initiates
      ER stress-associated apoptotic pathways, and 4-PBA pretreatment protected the
      cardiomyocytes from I/R-induced cell death. To the best of our knowledge, the
      present study is the first to report on the cell repair mechanism of 4-PBA
      against I/R damage in cardiomyocytes based on ER stress-associated apoptotic
      pathways. 

PMID- 27035224
TI  - Screening for genes and subnetworks associated with pancreatic cancer based on
      the gene expression profile.
AB  - The present study aimed to screen for potential genes and subnetworks associated
      with pancreatic cancer (PC) using the gene expression profile. The expression
      profile GSE 16515 was downloaded from the Gene Expression Omnibus database, which
      included 36 PC tissue samples and 16 normal samples. Limma package in R language
      was used to screen differentially expressed genes (DEGs), which were grouped as
      up- and downregulated genes. Then, PFSNet was applied to perform subnetwork
      analysis for all the DEGs. Moreover, Gene Ontology (GO) and REACTOME pathway
      enrichment analysis of up- and downregulated genes was performed, followed by
      protein-protein interaction (PPI) network construction using Search Tool for the
      Retrieval of Interacting Genes Search Tool for the Retrieval of Interacting
      Genes. In total, 1,989 DEGs including 1,461 up- and 528 downregulated genes were
      screened out. Subnetworks including pancreatic cancer in PC tissue samples and
      intercellular adhesion in normal samples were identified, respectively. A total
      of 8 significant REACTOME pathways for upregulated DEGs, such as hemostasis and
      cell cycle, mitotic were identified. Moreover, 4 significant REACTOME pathways
      for downregulated DEGs, including regulation of beta-cell development and
      transmembrane transport of small molecules were screened out. Additionally, DEGs
      with high connectivity degrees, such as CCNA2 (cyclin A2) and PBK (PDZ binding
      kinase), of the module in the protein-protein interaction network were mainly
      enriched with cell-division cycle. CCNA2 and PBK of the module and their relative
      pathway cell-division cycle, and two subnetworks (pancreatic cancer and
      intercellular adhesion subnetworks) may be pivotal for further understanding of
      the molecular mechanism of PC. 

PMID- 27035225
TI  - The hypolipidemic action of a diet supplemented with p,p'-methoxyl-diphenyl
      diselenide is not directly related to its antioxidant property.
AB  - The present study investigated whether a p,p'-methoxyl-diphenyl diselenide
      (MeOPhSe)2-supplemented diet causes toxicity in rats. A second aim of this study
      was to determine whether a 10 ppm (MeOPhSe)2-supplemented diet has hypolipidemic
      effect on Triton WR-1339-induced hyperlipidemia in rats. To rule out the
      antioxidant property of (MeOPhSe)2 in its hypolipidemic action, parameters of
      oxidative stress were carried out. Wistar rats were fed with 3, 10, or 30 ppm of
      (MeOPhSe)2-supplemented diet for 30 days. None of (MeOPhSe)2-supplemented diets
      caused alteration in general parameters of toxicity and lipid profile of rats.
      The hypolipidemic effect of 10 ppm of (MeOPhSe)2-supplemented diet on rats
      treated with Triton WR-1339 (400 mg/kg, intraperitoneal) was investigated. The
      (MeOPhSe)2-supplemented diet partially protected against the levels of total
      cholesterol (TC) and non-HDL-C and reduced the atherogenic index (AI) increased
      by Triton WR-1339 in rats. A positive correlation between TC and triglyceride
      levels (r = 0.679) and non-HDL-C levels (r = 0.929) and AI (r = 0.889) was
      demonstrated. Triton WR-1339 altered parameters of oxidative stress in livers of
      rats but (MeOPhSe)2-supplemented diet did not protect against these alterations.
      The results demonstrated that the hypolipidemic action of (MeOPhSe)2-supplemented
      diet is not directly related to its antioxidant property and devoid of systemic
      toxicity in rats at the parameters analyzed. 

PMID- 27035226
TI  - Inhibition of RANKL-induced osteoclast differentiation through the downregulation
      of c-Fos and NFATc1 by Eremochloa ophiuroides (centipedegrass) extract.
AB  - Osteoclasts, derived from hematopoietic stem cells, are specialized macrophages
      and have a homeostatic role in skeletal modeling and remodeling with bone-forming
      osteoblasts. However, excessive osteoclast activity induces bone diseases,
      including osteoporosis, periodontitis and rheumatoid arthritis. Natural
      substances have received attention as therapeutic drugs in human diseases. In the
      current study, cells isolated from mouse bone marrow, and a mouse model, were
      used to determine the effect of centipedegrass extract (CGE) on osteoclasts.
      Multiple concentrations of CGE were administered to bone marrow cells for 24-72
      hours and, for the in vivo study, mice were treated with CGE for 8 days. The
      effects of CGE on transcription and translation of osteoclast-associated
      molecules were then determined using reverse transcription-polymerase chain
      reaction and immunoblotting, respectively. In the present study it was shown that
      CGE extracted from Eremochloa ophiuroides (centipedegrass) inhibited receptor
      activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast
      differentiation in bone marrow macrophages, without cytotoxicity, in a dose
      dependent manner. CGE decreased the expression levels of osteoclast-specific
      genes, including matrix metalloproteinase-9, osteoclast-associated immunoglobulin
      like receptor and cathepsin K, however, CGE had no inhibitory effect on the
      expression levels of mitogen-activated protein kinases, nuclear factor-kappaB and
      Akt. Furthermore, the protein and RNA levels of RANKL-induced c-Fos and nuclear
      factor of activated T-cell cytoplasmic 1 were suppressed by CGE. These results
      indicated that CGE may serve as a useful drug in the prevention of bone loss. 

PMID- 27035227
TI  - MicroRNA-335 is downregulated in bladder cancer and inhibits cell growth,
      migration and invasion via targeting ROCK1.
AB  - The expression of microRNA-335 (miR-335) has been demonstrated to be
      downregulated in numerous types of cancer. Thus far, no previous studies have
      investigated the miR-335 expression in bladder cancer. In the present study, the
      expression and effects of miR-335 were assessed in bladder cancer. The results of
      the present study provided, to the best of our knowledge, the first evidence that
      miR-335 is downregulated in the tumor tissue of patients with bladder cancer.
      Following transfection of miR-335, MTT, cell migration and invasion, luciferase
      and western blot assays were conducted in bladder cancer cell lines. The results
      demonstrated that miR-335 inhibited cell proliferation, migration and invasion in
      T24 and EJ cells. In addition, the results suggested that miR-335 directly
      targets Rho-associated protein kinase 1 (ROCK1) in bladder cancer. The present
      study provided a novel therapeutic target, the miR-335/ROCK1 axis in bladder
      cancer. The suggested approach will be beneficial in developing an effective
      treatment against bladder cancer. 

PMID- 27035228
TI  - Transfection of chondromodulin I into human breast cancer cells and its effect on
      the inhibition of cancer cell growth.
AB  - Breast cancer affects one in every eight women, and has been associated with
      higher rates of female mortality than any other cancer type, with the exception
      of lung cancer. It has been reported that chondromodulin I (ChM-I) was able to
      suppress tumor angiogenesis and growth in vivo. In order to investigate the
      antitumor action of ChM-I on human breast cancer cells, a plasmid expressing ChM
      I was constructed and transfected into human breast cancer cells using an
      adenoviral vector. Reverse transcription-polymerase chain reaction detected ChM-I
      expression in human breast cancer cell lines, whereas no expression was detected
      in the control groups. In order to assess the effect of ChM-I on human breast
      cancer cells, cell counting kit-8 (CCK-8) and colony formation analyses were used
      to detect tumor cell proliferation, and the proliferation of ChM-I-transfected
      cells was significantly reduced, as compared with the control. In addition, the
      mRNA expression levels of cell cycle-associated genes in ChM-I-transfected cells
      were significantly decreased, as compared with the control, which suggested that
      ChM-I transfection was able to inhibit the expression of genes associated with
      the cell cycle. The results of the present study indicated that ChM-I was able to
      inhibit the growth of breast cancer cells; thus suggesting that ChM-I may have
      potential clinical applications in the treatment of breast cancer. 

PMID- 27035229
TI  - CGRP may regulate bone metabolism through stimulating osteoblast differentiation
      and inhibiting osteoclast formation.
AB  - Calcitonin-gene-related peptide (CGRP) is a neuropeptide, which is widely
      distributed throughout the central and peripheral nervous systems. Numerous
      mechanisms underlying the action of CGRP in osteoblast-associated cells have been
      suggested for bone growth and metabolism. The present study was designed to
      closely investigate the osteoblast- and osteoclast-associated mechanisms of the
      effect of CGRP administration on bone metabolism in primary osteoblasts. Primary
      osteoblasts were obtained from newborn rabbit calvaria and incubated with
      different concentrations of human CGRP (hCGRP), hCGRP and hCGRP (8-37), or
      without treatment as a control. Intracellular calcium (Ca2+) and cyclic adenosine
      monophosphate (cAMP) were detected following treatment, as well as the expression
      levels of osteoblast differentiation markers, including activating transcription
      factor-4 (ATF4) and osteocalcin (OC), and receptor activator of nuclear factor
      kappaB ligand (RANKL) and osteoprotegerin (OPG). The isolated primary osteoblasts
      were found to stain positively for ALP. hCGRP treatment had no significant effect
      on transient intracellular Ca2+ in the osteoblasts. Treatment of the osteoblasts
      with hCGRP led to elevations in the expression levels of cAMP, ATF4 and OPG, and
      downregulation in the expression of RANKL, in a dose-dependent manner. These
      effects were markedly reversed by the addition of hCGRP (8-37). The results of
      the present study demonstrated that CGRP administration not only stimulated
      osteoblast differentiation, as demonstrated by upregulated expression levels of
      ATF4 and OC in the hCGRP-treated osteoblasts, but also inhibited OPG/RANKL
      regulated osteoclastogenesis. CGRP may act as a modulator of bone metabolism
      through osteoblast and osteoclast-associated mechanisms, which result in
      osteoblast formation with subsequent activation of bone formation. 

PMID- 27035230
TI  - Profiling lethal factor interacting proteins from human stomach using T7 phage
      display screening.
AB  - The anthrax lethal factor (LF) is a zinc dependent metalloproteinase that cleaves
      the majority of mitogen-activated protein kinase kinases and a member of NOD-like
      receptor proteins, inducing cell apoptosis. Despite efforts to fully understand
      the Bacillus anthracis toxin components, the gastrointestinal (GI) anthrax
      mechanisms have not been fully elucidated. Previous studies demonstrated gastric
      ulceration, and a substantial bacterial growth rate in Peyer's patches. However,
      the complete molecular pathways of the disease that results in tissue damage by
      LF proteolytic activity remains unclear. In the present study, to identify the
      profile of the proteins potentially involved in GI anthrax, protein-protein
      interactions were investigated using human stomach T7 phage display (T7PD) cDNA
      libraries. T7PD is a high throughput technique that allows the expression of
      cloned DNA sequences as peptides on the phage surface, enabling the selection and
      identification of protein ligands. A wild type and mutant LF (E687A) were used to
      differentiate interaction sites. A total of 124 clones were identified from 194
      interacting-phages, at both the DNA and protein level, by in silico analysis.
      Databases revealed that the selected candidates were proteins from different
      families including lipase, peptidase-A1 and cation transport families, among
      others. Furthermore, individual T7PD candidates were tested against LF in order
      to detect their specificity to the target molecule, resulting in 10 LF
      interacting peptides. With a minimum concentration of LF for interaction at 1
      ug/ml, the T7PD isolated pepsin A3 pre-protein (PAP) demonstrated affinity to
      both types of LF. In addition, PAP was isolated in various lengths for the same
      protein, exhibiting common regions following PRALINE alignment. These findings
      will help elucidate and improve the understanding of the molecular pathogenesis
      of GI anthrax, and aid in the development of potential therapeutic agents. 

PMID- 27035231
TI  - Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway.
AB  - In response to various cellular stresses, p53 exerts its tumor suppressive
      effects such as apoptosis, cell cycle arrest, and senescence through the
      induction of its target genes. Recently, p53 was shown to control cellular
      homeostasis by regulating energy metabolism, glycolysis, antioxidant effect, and
      autophagy. However, its function in inositol synthesis was not reported. Through
      a microarray screening, we found that five genes related with myo-inositol
      metabolism were induced by p53. DNA damage enhanced intracellular myo-inositol
      content in HCT116 p53+/+ cells, but not in HCT116 p53-/- cells. We also indicated
      that inositol 3-phosphate synthase (ISYNA1) which encodes an enzyme essential for
      myo-inositol biosynthesis as a direct target of p53. Activated p53 regulated
      ISYNA1 expression through p53 response element in the seventh exon. Ectopic
      ISYNA1 expression increased myo-inositol levels in the cells and suppressed tumor
      cell growth. Knockdown of ISYNA1 caused resistance to adriamycin treatment,
      demonstrating the role of ISYNA1 in p53-mediated growth suppression. Furthermore,
      ISYNA1 expression was significantly associated with p53 mutation in bladder,
      breast cancer, head and neck squamous cell carcinoma, lung squamous cell
      carcinoma, and pancreatic adenocarcinoma. Our findings revealed a novel role of
      p53 in myo-inositol biosynthesis which could be a potential therapeutic target. 

PMID- 27035232
TI  - Recombinant adeno-associated virus-delivered anginex inhibits angiogenesis and
      growth of HUVECs by regulating the Akt, JNK and NF-kappaB signaling pathways.
AB  - Anginex is an artificial synthetic small molecule beta-sheet-forming peptide
      shown to have anti-angiogenesis and antitumor effects in various solid tumors.
      However, its molecular mechanism remains largely unclear and efficient delivery
      methods for anginex remains to be developed. We report on the development of
      recombinant adeno-associated virus (rAAV2)-delivered anginex and the underlying
      mechanism of anti-angiogenesis and antitumor effects of anginex. We have
      successfully developed the rAAV2 vector to efficiently express anginex (rAAV2
      anginex). Transduction of rAAV2-anginex significantly induced apoptosis, and
      inhibited the proliferation, migration, invasion and tube formation of human
      umbilical vein endothelial cells in vitro. Western blot analysis revealed that
      rAAV2-anginex inhibited the phosphorylation of Akt, while inducing the
      phosphorylation of JNK and activation of the NF-kappaB signaling pathway. In an
      in vivo CAM assay and xenograft model of SKOV3, rAAV2-anginex significantly
      reduced microvessel density (MVD) and vascular endothelial growth factor 165
      (VEGF165), as demonstrated by immunohistochemistry analysis. Importantly, rAAV2
      anginex inhibited tumor growth in an ovarian cancer SKOV3 cell nude mouse
      xenograft model. Our results suggest that rAAV2-anginex may inhibit tumor
      angiogenesis and growth through regulating Akt, JNK and NF-kappaB signaling
      pathways. 

PMID- 27035233
TI  - Attenuation of liver fibrosis by herbal compound 861 via upregulation of BMP
      7/Smad signaling in the bile duct ligation model rat.
AB  - Herbal compound 861 (Cpd 861) exerts an anti-fibrotic effect in patients with
      hepatic fibrosis; however, the anti-fibrotic mechanism has yet to be fully
      elucidated. The present study aimed to explore the mechanistic basis for the anti
      fibrotic effect, with a focus on bone morphogenetic protein 7 (BMP-7)/Smad
      signaling in a bile duct ligation (BDL)-induced liver fibrosis rat model.
      Following the induction of hepatic fibrosis, rats induced by BDL were treated
      with 9 g/kg Cpd 861 daily or an equal volume of saline for 28 days. Serum samples
      were prepared for monitoring the levels of alanine transaminase, aspartate
      transaminase and total bilirubin, and direct bilirubin analyses and liver samples
      were used to investigate gene expression, protein localization and protein
      expression analysis using real-time quantitative polymerase chain reaction,
      immunohistochemistry and western blotting. The results revealed the attenuation
      of liver fibrosis by Cpd 861 in the histological and biochemical experiments. BMP
      7 and phospho (p)-Smad1/5/8 were localized predominantly in the cytoplasm of
      hepatocytes. In comparison with the saline-treated BDL rats, Cpd 861 markedly
      upregulated the gene expression of BMP-7 and Smad5, as well as the protein
      expression of BMP-7 and Smad1/5. In addition, p-Smad1/5/8 protein expression was
      markedly increased by Cpd 861 in the BDL model. These results indicated that Cpd
      861 alleviates hepatic fibrosis possibly via the upregulation and activation of
      BMP-7/Smad signaling in hepatic fibrotic rats. 

PMID- 27035234
TI  - Clinical, pathological and genetic characteristics of autosomal dominant
      inherited dynamin 2 centronuclear myopathy.
AB  - The aim of the present study was to report on a family with pathologically and
      genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM).
      In addition, this study aimed to investigate the clinical, pathological and
      molecular genetic characteristics of the disease. This pedigree was traced back
      three generations, four patients underwent neurological examination, two patients
      underwent muscle biopsy, and eight family members were subjected to dynamin 2
      (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family
      members, of which four patients exhibited DNM2 mutation-specific clinical and
      pathological features. Lower extremity weakness was the predominant symptom of
      these patients, however, proximal and distal lower extremity involvement was
      inconsistent. All patients exhibited marked systematic muscle atrophy and various
      degrees of facial muscle involvement. The patients presented the typical
      pathological changes of CNM, and their muscle tissues were heavily replaced by
      adipose tissue, with clustered distribution of muscle fibers as another notable
      feature. DNM2-CNM patients of this pedigree exhibited heterogeneous clinical and
      pathological features, providing a basis for further molecular genetic analysis.

PMID- 27035235
TI  - Suppression of STAT5b in pancreatic cancer cells leads to attenuated gemcitabine
      chemoresistance, adhesion and invasion.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid
      malignancies, and there is an urgent need for new therapeutic strategies based on
      the molecular biology of PDAC. Signal transducers and activators of transcription
      5 (STAT5) are known to be activated in a variety of malignancies and involved in
      tumor proliferation, apoptosis, and invasion, whereas the expression and
      biological role of STAT5b in PDAC are less clearly defined. In the present study,
      we examined the expression and role of STAT5b in human pancreatic cancer cell
      lines. Expressions of STAT5b mRNA and protein were detected in eight kinds of
      pancreatic cancer cells. Confocal microscopy and western blot analysis indicated
      that STAT5b is localized in both cytoplasm and nuclei. Immunoprecipitation
      analysis revealed tyrosine phosphorylation of STAT5b in pancreatic cancer cells.
      These results indicate that STAT5b in pancreatic cancer cells is constitutively
      activated. STAT5b shRNA clones in PANC-1 cells, which express relatively high
      levels of STAT5b, exhibited reduced chemoresistance against gemcitabine, adhesion
      and invasion compared to sham. On the other hand, AsPC-1 and BxPC3 cells, which
      express relatively low levels of STAT5b, exhibited reduced chemoresistance
      compared to PANC-1 cells. Moreover, STAT5b overexpression clones in AsPC-1 cells
      exhibited increased chemoresistance compared to sham. STAT5b shRNA clones in PANC
      1 cells were more sensitive to the proapoptotic actions of gemcitabine, as
      evidenced by PARP and cleaved caspase-3 activation. Gemcitabine also
      significantly reduced Bcl-xL levels in the STAT5b shRNA-expressing cells. We also
      investigated the clinicopathological characteristics of STAT5b expression of
      PDAC. Although a significant correlation between STAT5b expression and overall
      survival rates was not observed, a significant correlation with main pancreatic
      duct invasion was observed. These findings suggest that STAT5b confers
      gemcitabine chemoresistance and promotes cell adherence and invasiveness in
      pancreatic cancer cells. Targeting STAT5b may lead to novel therapeutic
      strategies for PDAC. 

PMID- 27035236
TI  - Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in
      Experimental Acute Respiratory Distress Syndrome.
AB  - OBJECTIVE: Volutrauma and atelectrauma promote ventilator-induced lung injury,
      but their relative contribution to inflammation in ventilator-induced lung injury
      is not well established. The aim of this study was to determine the impact of
      volutrauma and atelectrauma on the distribution of lung inflammation in
      experimental acute respiratory distress syndrome. DESIGN: Laboratory
      investigation. SETTING: University-hospital research facility. SUBJECTS: Ten pigs
      (five per group; 34.7-49.9 kg) INTERVENTIONS: : Animals were anesthetized and
      intubated, and saline lung lavage was performed. Lungs were separated with a
      double-lumen tube. Following lung recruitment and decremental positive end
      expiratory pressure trial, animals were randomly assigned to 4 hours of
      ventilation of the left (ventilator-induced lung injury) lung with tidal volume
      of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above
      the level where dynamic compliance increased more than 5% during positive end
      expiratory pressure trial (volutrauma); or 2) low positive end-expiratory
      pressure to achieve driving pressure comparable with volutrauma (atelectrauma).
      The right (control) lung was kept on continuous positive airway pressure of 20 cm
      H2O, and CO2 was partially removed extracorporeally. MEASUREMENTS AND MAIN
      RESULTS: Regional lung aeration, specific [F]fluorodeoxyglucose uptake rate, and
      perfusion were assessed using computed and positron emission tomography.
      Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in the ventilated
      lung compared with atelectrauma (median [interquartile range], 0.017 [0.014
      0.025] vs 0.013 min [0.010-0.014 min]; p < 0.01), mainly in central lung regions.
      Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in ventilator-induced
      lung injury versus control lung (0.017 [0.014-0.025] vs 0.011 min [0.010-0.016
      min]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood
      fraction at similar perfusion and increased normally as well as hyperaerated lung
      compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and
      nonaerated lung compartments, and tidal recruitment. Driving pressure increased
      in atelectrauma. CONCLUSIONS: In this model of acute respiratory distress
      syndrome, volutrauma promoted higher lung inflammation than atelectrauma at
      comparable low tidal volume and lower driving pressure, suggesting that static
      stress and strain are major determinants of ventilator-induced lung injury.

PMID- 27035237
TI  - Low Tidal Volume Ventilation Use in Acute Respiratory Distress Syndrome.
AB  - OBJECTIVE: Low tidal volume ventilation lowers mortality in the acute respiratory
      distress syndrome. Previous studies reported poor low tidal volume ventilation
      implementation. We sought to determine the rate, quality, and predictors of low
      tidal volume ventilation use. DESIGN: Retrospective cross-sectional study.
      SETTING: One academic and three community hospitals in the Chicago region.
      PATIENTS: A total of 362 adults meeting the Berlin Definition of acute
      respiratory distress syndrome consecutively admitted between June and December
      2013. MEASUREMENTS AND MAIN RESULTS: Seventy patients (19.3%) were treated with
      low tidal volume ventilation (tidal volume < 6.5 mL/kg predicted body weight) at
      some time during mechanical ventilation. In total, 22.2% of patients requiring an
      FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and
      plateau pressure greater than 30 cm H2O received low tidal volume ventilation.
      The entire cohort received low tidal volume ventilation 11.4% of the time
      patients had acute respiratory distress syndrome. Among patients who received low
      tidal volume ventilation, the mean (SD) percentage of acute respiratory distress
      syndrome time it was used was 59.1% (38.2%), and 34% waited more than 72 hours
      prior to low tidal volume ventilation initiation. Women were less likely to
      receive low tidal volume ventilation, whereas sepsis and FIO2 greater than 40%
      were associated with increased odds of low tidal volume ventilation use. Four
      attending physicians (6.2%) initiated low tidal volume ventilation within 1 day
      of acute respiratory distress syndrome onset for greater than or equal to 50% of
      their patients, whereas 34 physicians (52.3%) never initiated low tidal volume
      ventilation within 1 day of acute respiratory distress syndrome onset. In total,
      54.4% of patients received a tidal volume less than 8 mL/kg predicted body
      weight, and the mean tidal volume during the first 72 hours after acute
      respiratory distress syndrome onset was never less than 8 mL/kg predicted body
      weight. CONCLUSIONS: More than 12 years after publication of the landmark low
      tidal volume ventilation study, use remains poor. Interventions that improve
      adoption of low tidal volume ventilation are needed.

PMID- 27035238
TI  - Osmotherapy With Hypertonic Saline Attenuates Global Cerebral Edema Following
      Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4.
AB  - OBJECTIVES: We tested the hypothesis that osmotherapy with hypertonic saline
      attenuates cerebral edema following experimental cardiac arrest and
      cardiopulmonary resuscitation by exerting its effect via the perivascular pool of
      aquaporin-4. We used mice with targeted disruption of the gene encoding alpha
      syntrophin (alpha-Syn) that demonstrate diminished perivascular aquaporin-4 pool
      but retain the non-endfoot and ependymal pools. DESIGN: Laboratory animal study.
      SETTING: University animal research laboratory. INTERVENTIONS: Isoflurane
      anesthetized adult male wild-type C57B/6 or alpha-Syn mice were subjected to
      cardiac arrest/cardiopulmonary resuscitation and treated with either a continuous
      IV infusion of 0.9% saline or various concentrations of hypertonic saline. Serum
      osmolality, regional brain water content, blood-brain barrier disruption, and
      aquaporin-4 protein expression were determined at 24 hours after cardiac
      arrest/cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Hypertonic
      saline (7.5%) treatment significantly attenuated water content in the
      caudoputamen complex and cortex compared with 0.9% saline treatment in wild-type
      mice subjected to cardiac arrest/cardiopulmonary resuscitation. In contrast, in
      alpha-Syn mice subjected to cardiac arrest/cardiopulmonary resuscitation, 7.5%
      hypertonic saline treatment did not attenuate water content. Treatment with 7.5%
      hypertonic saline attenuated blood-brain barrier disruption at 24 hours following
      cardiac arrest/cardiopulmonary resuscitation in wild-type mice but not in alpha
      Syn mice. Total aquaporin-4 protein expression was not different between 0.9%
      saline and hypertonic saline-treated wild-type mice. CONCLUSIONS: Following
      experimental cardiac arrest/cardiopulmonary resuscitation: 1) continuous
      hypertonic saline therapy maintained to achieve serum osmolality of ~ 350 mOsm/L
      is beneficial for the treatment of cerebral edema; 2) perivascular pool of
      aquaporin-4 plays a critical role in water egress from brain; and 3) hypertonic
      saline attenuates blood-brain barrier disruption via perivascular aquaporin-4
      pool.

PMID- 27035239
TI  - Age, PaO2/FIO2, and Plateau Pressure Score: A Proposal for a Simple Outcome Score
      in Patients With the Acute Respiratory Distress Syndrome.
AB  - OBJECTIVES: Although there is general agreement on the characteristic features of
      the acute respiratory distress syndrome, we lack a scoring system that predicts
      acute respiratory distress syndrome outcome with high probability. Our objective
      was to develop an outcome score that clinicians could easily calculate at the
      bedside to predict the risk of death of acute respiratory distress syndrome
      patients 24 hours after diagnosis. DESIGN: A prospective, multicenter,
      observational, descriptive, and validation study. SETTING: A network of
      multidisciplinary ICUs. PATIENTS: Six-hundred patients meeting Berlin criteria
      for moderate and severe acute respiratory distress syndrome enrolled in two
      independent cohorts treated with lung-protective ventilation. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Using individual demographic, pulmonary, and
      systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we
      derived our prediction score in 300 acute respiratory distress syndrome patients
      based on stratification of variable values into tertiles, and validated in an
      independent cohort of 300 acute respiratory distress syndrome patients. Primary
      outcome was in-hospital mortality. We found that a 9-point score based on
      patient's age, PaO2/FIO2 ratio, and plateau pressure at 24 hours after acute
      respiratory distress syndrome diagnosis was associated with death. Patients with
      a score greater than 7 had a mortality of 83.3% (relative risk, 5.7; 95% CI, 3.0
      11.0), whereas patients with scores less than 5 had a mortality of 14.5% (p <
      0.0000001). We confirmed the predictive validity of the score in a validation
      cohort. CONCLUSIONS: A simple 9-point score based on the values of age, PaO2/FIO2
      ratio, and plateau pressure calculated at 24 hours on protective ventilation
      after acute respiratory distress syndrome diagnosis could be used in real time
      for rating prognosis of acute respiratory distress syndrome patients with high
      probability.

PMID- 27035240
TI  - Automatic Classification of Sedation Levels in ICU Patients Using Heart Rate
      Variability.
AB  - OBJECTIVE: To explore the potential value of heart rate variability features for
      automated monitoring of sedation levels in mechanically ventilated ICU patients.
      DESIGN: Multicenter, pilot study. SETTING: Several ICUs at Massachusetts General
      Hospital, Boston, MA. PATIENTS: Electrocardiogram recordings from 40 mechanically
      ventilated adult patients receiving sedatives in an ICU setting were used to
      develop and test the proposed automated system. MEASUREMENTS AND MAIN RESULTS:
      Richmond Agitation-Sedation Scale scores were acquired prospectively to assess
      patient sedation levels and were used as ground truth. Richmond Agitation
      Sedation Scale scores were grouped into four levels, denoted "unarousable"
      (Richmond Agitation- Sedation Scale = -5, -4), "sedated" (-3, -2, -1), "awake"
      (0), "agitated" (+1, +2, +3, +4). A multiclass support vector machine algorithm
      was used for classification. Classifier training and performance evaluations were
      carried out using leave-oneout cross validation. An overall accuracy of 69% was
      achieved for discriminating between the four levels of sedation. The proposed
      system was able to reliably discriminate (accuracy = 79%) between sedated
      (Richmond Agitation-Sedation Scale < 0) and nonsedated states (Richmond Agitation
      Sedation Scale > 0). CONCLUSIONS: With further refinement, the methodology
      reported herein could lead to a fully automated system for depth of sedation
      monitoring. By enabling monitoring to be continuous, such technology may help
      clinical staff to monitor sedation levels more effectively and to reduce
      complications related to over- and undersedation.

PMID- 27035241
TI  - Routine Chest Radiography Is Not Necessary After Ultrasound-Guided Right Internal
      Jugular Vein Catheterization.
AB  - OBJECTIVES: Central venous catheter placement is a common procedure performed on
      critically ill patients. Routine postprocedure chest radiographs are considered
      standard practice. We hypothesize that the rate of clinically relevant
      complications detected on chest radiographs following ultrasound-guided right
      internal jugular vein catheterization is exceedingly low. DESIGN: Retrospective
      chart review. SETTING: Adult ICUs, emergency departments, and general practice
      units at an academic tertiary care hospital system. PATIENTS: All 1,322
      ultrasound-guided right internal jugular vein central venous catheter attempts at
      an academic tertiary care hospital system over a 1-year period. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Data from standardized procedure notes and
      postprocedure chest radiographs were extracted and individually reviewed to
      verify the presence of pneumothorax or misplacement, and any intervention
      performed for either complication. The overall success rate of ultrasound-guided
      right internal jugular vein central venous catheter placement was 96.9% with an
      average of 1.3 attempts. There was only one pneumothorax (0.1% [95% CI, 0-0.4%]),
      and the rate of catheter misplacement requiring repositioning or replacement was
      1.0% (95% CI, 0.6-1.7%). There were no arterial placements found on chest
      radiographs. Multivariate regression analysis showed no correlation between high
      risk patient characteristics and composite complication rate. CONCLUSIONS: In a
      large teaching hospital system, the overall rate of clinically relevant
      complications detected on chest radiographs following ultrasound-guided right
      internal jugular vein catheterization is exceedingly low. Routine chest
      radiograph after this common procedure is an unnecessary use of resources and may
      delay resuscitation of critically ill patients.

PMID- 27035242
TI  - Disposition kinetics and metabolism of nicotine and cotinine in African American
      smokers: impact of CYP2A6 genetic variation and enzymatic activity.
AB  - OBJECTIVE: The rate of nicotine metabolism, determined primarily by CYP2A6
      activity, influences tobacco dependence and smoking-induced disease risk. The
      prevalence of CYP2A6 gene variants differs by race, with greater numbers in
      African Americans compared with Caucasians. We studied nicotine disposition
      kinetics and metabolism by the CYP2A6 genotype and enzymatic activity, as
      measured by the nicotine metabolite ratio (NMR), in African American smokers.
      METHODS: Participants were administered intravenous infusions of deuterium
      labeled nicotine and cotinine. Plasma and urine concentrations of nicotine and
      metabolites were measured and pharmacokinetic parameters were estimated. RESULTS:
      Pharmacokinetic parameters and urine metabolite excretion data were analyzed by
      CYP2A6 genotype and by NMR. A number of gene variants were associated with
      markedly reduced nicotine and cotinine clearances. NMR was strongly correlated
      with nicotine (r=0.72) and cotinine (r=0.80) clearances. Participants with higher
      NMR excreted significantly greater nicotine C-oxidation and lower non-C-oxidation
      products compared with lower NMR participants. CONCLUSION: CYP2A6 genotype, NMR,
      and nicotine pharmacokinetic data may inform studies of individual differences in
      smoking behavior and biomarkers of nicotine exposure.

PMID- 27035243
TI  - Understanding community-acquired respiratory tract infections: new concepts of
      disease pathogenesis and new management strategies.

PMID- 27035244
TI  - Interventional pulmonology: current state of the art.

PMID- 27035246
TI  - Ultrasound in Neuromuscular Disorders.

PMID- 27035247
TI  - Ultrasound in Neuromuscular Disorders.
AB  - Electrodiagnosis with nerve conduction studies and needle electromyography has
      been the standard method of diagnosis of neuromuscular conditions for over 80
      years. Although ultrasound technology has been in existence for approximately the
      same time, application of this technology to assessment of the neuromuscular
      system only began in the 1980s. In the past 2 decades-mainly because of advances
      in resolution enabled by high frequency transducers and improved image processing
      ultrasound has enabled the real-time, morphologic evaluation of focal and diffuse
      neuropathies, motor neuron diseases, and myopathies. Although methods of nerve
      and muscle assessment continue to evolve (i.e., Doppler imaging to evaluate
      intraneural and intramuscular blood flow), nerves have most commonly been
      evaluated based on their cross-sectional area, which seems to correlate with
      nerve swelling and pathology, particularly in focal and also in some diffuse
      neuropathies. Qualitative and more recently quantitative measures of muscle
      echogenicity have been used in the assessment of myopathies and motor neuron
      diseases. Collection of normal values in heterogeneous populations, extremes of
      age and patients with differing anthropometric profiles, has helped develop
      tables of normal values, thereby allowed ultrasound measurements to be judged
      against a reference standard, as has previously been established for nerve
      conduction studies. 

PMID- 27035248
TI  - Neuromuscular Ultrasound in the Assessment of Polyneuropathies and Motor Neuron
      Disease.
AB  - Neuromuscular ultrasound is an emerging technology for the evaluation of
      conditions affecting nerve and muscle, with most of the research focusing on
      focal neuropathies. Despite this focus, researchers have also investigated the
      ultrasonographic changes that occur in the nerves and muscles of those with more
      diffuse polyneuropathies and motor neuron diseases, and this review will detail
      the findings in these conditions. Specific findings are discussed in this
      article, but general themes will also be presented and include the following:
      hereditary polyneuropathies show diffuse nerve enlargement, whereas immune
      mediated polyneuropathies show more patchy involvement; nerve enlargement is more
      profound in demyelinating than axonal polyneuropathies; and muscle changes in
      motor neuron diseases include heterogeneous increases in echogenicity, atrophy,
      readily detectable fasciculations, and increased subcutaneous tissue thickness. 

PMID- 27035249
TI  - Ultrasound of Focal Neuropathies.
AB  - Focal neuropathies represent the most common indication for referral to
      electrodiagnostic laboratories. The etiologies range from chronic compression, as
      might be seen in carpal tunnel syndrome, to acute traumatic nerve injuries that
      require rapid intervention. The gold standard for diagnosis, electrodiagnostic
      testing, cannot provide the complementary anatomical information necessary to
      guide accurate diagnosis and treatment. An expanding body of literature supports
      the use of neuromuscular ultrasound as a standard component for evaluating focal
      neuropathies. In the current review, the role of ultrasound in both common and
      unusual compression neuropathies is reviewed, along with the use of ultrasound in
      traumatic nerve injury. The evidence demonstrates that nerve ultrasound has an
      essential, complementary role with electrodiagnostic testing. 

PMID- 27035250
TI  - Ultrasound in the Assessment of Myopathic Disorders.
AB  - Neuromuscular ultrasound (US) augments a careful physical examination and
      electrodiagnostic evaluation in the evaluation of suspected myopathy. Ultrasound
      evaluation of muscle can identify abnormal echo intensity, size, and movement.
      Because it is painless and noninvasive, US can be used to evaluate multiple
      muscles to direct the electrodiagnostic examination or muscle biopsy. Some
      patterns of muscle involvement can suggest specific etiologies. Most muscular
      dystrophies show homogenously increased muscle echo intensity with attenuation of
      the US signal, likely resultant from increased intramuscular fat and fibrosis.
      Inflammatory myopathies can also show homogenously increased echogenicity but
      lack the signal attenuation seen in muscular dystrophies. In contrast,
      denervation can show "moth-eaten," atrophic muscles with fasciculations. Advanced
      age and obesity also impacts muscle size and echo intensity and can hamper
      efforts to detect mild pathologies. The sensitivity and specificity of US for
      detecting neuromuscular disease have been best studied in children and depend on
      the type and severity of the disorder. In general, muscle US yields sensitivities
      and specificities of 67% to 100% for detecting neuromuscular disorders in
      children and is similar to electromyogram for detection of myopathy. Ultrasound
      is most sensitive for detecting muscular dystrophies and is less sensitive in
      metabolic myopathies and very young children. 

PMID- 27035251
TI  - Ultrasound in the Assessment of Respiration.
AB  - Electromyographers are often asked to evaluate patients presenting with dyspnea
      or respiratory failure, to rule out an underlying neuromuscular cause for those
      symptoms. Available tools for diagnosing such patients include pulmonary function
      tests, transdiaphragmatic pressure testing, various imaging modalities, phrenic
      nerve conduction studies, and diaphragm electromyography. Phrenic nerve
      conduction studies and diaphragm electromyography are technically challenging and
      can be limited by both false positive and false negative results. Integration of
      diagnostic ultrasound can enhance the accuracy and safety of diaphragm
      electromyography, and improve sensitivity and specificity of phrenic nerve
      conduction studies. In addition, brightness-mode ultrasound imaging of the
      diaphragm allows for measurement of muscle thickness and contractility, and is a
      very sensitive and specific diagnostic test in this setting. This article will
      review the electromyographer's approach to patients presenting with respiratory
      symptoms, with a focus on neuromuscular ultrasound. 

PMID- 27035252
TI  - Carboxylic Acid Functionalized Clathrochelate Complexes: Large, Robust, and Easy
      to-Access Metalloligands.
AB  - Polycarboxylate ligands are among the most important building blocks for the
      synthesis of metal-organic frameworks (MOFs). The ability to access these ligands
      in an efficient way is of key importance for future applications of MOFs. Here,
      we demonstrate that mono- and dinuclear clathrochelate complexes are versatile
      scaffolds for the preparation of polytopic carboxylate ligands. The largely inert
      clathrochelate complexes have a trigonal-bipyramidal shape. The synthesis of
      functionalized clathrochelates with two, three, four, or five carboxylic acid
      groups in the ligand periphery can be achieved in a few steps from simple
      starting materials. Apart from being easily accessible, the metalloligands
      display interesting characteristics for applications in metallasupramolecular
      chemistry and materials science: they are rigid, large (up to 2.2 nm), and robust
      and they can show additional functions (e.g., fluorescence or extra charge)
      depending on the metal ion that is present in the clathrochelate core. The
      utility of these new metalloligands in MOF chemistry is demonstrated by the
      synthesis of zinc- and zirconium-based coordination polymers. The combination of
      Zn(NO3)2 with clathrochelates having two or three carboxylic acid groups gives
      MOFs in which the clathrochelate ligands are connected by Zn4O clusters or zinc
      paddlewheel links. The structures of the resulting two- and three-dimensional
      networks could be established by single-crystal X-ray crystallography. The
      reaction of carboxylic acid functionalized clathrochelates with ZrCl4 gives
      amorphous powders that display permanent porosity after solvent removal. 

PMID- 27035253
TI  - Influence of the structure on the collapse of poly(N-isopropylacrylamide)-based
      microgels: an insight by quantitative dielectric analysis.
AB  - The collapse of poly(N-isopropylacrylamide)/poly(acrylic acid) semi
      interpenetrating polymer network (PNIPAM/PAA SIPN) and poly(N-isopropylacrylamide
      co-acrylic acid) (P(NIPAM-co-AA)) microgel suspensions is studied by dielectric
      spectroscopy in a frequency range from 40 Hz to 110 MHz as a function of
      temperature. Dielectric measurements show that the structure affects the
      relaxation behavior of microgels: two relaxations (micro-Brownian motion and
      interfacial polarization at low frequency and counterion polarization at high
      frequency) are observed in the SIPN microgel whose charges mainly exist in
      domains and one relaxation (interfacial polarization) is observed in the
      copolymer microgel whose charges distribute in the whole network. A dielectric
      model is proposed to describe the collapsed microgel suspensions, from which some
      parameters, such as the volume fraction and the permittivity of microgels, were
      calculated using Hanai's equation. The temperature dependencies of these
      parameters show that the SIPN microgel has better low-temperature swelling
      properties and thermal responsiveness. This is caused by different polymer
      solvent and electrostatic repulsion interactions in different microgels. Compared
      with pure PNIPAM, the relationship of volume phase transition temperature (VPTT)
      is VPTTP(NIPAM-co-AA) > VPTTPNIPAM/PAA SIPN > VPTTPNIPAM, and it is explained
      from the viewpoint of interaction. Besides, the activation energy data prove that
      the structure influences the electrical properties of microgels, which is
      consistent with the results obtained from quantitative dielectric analysis.

PMID- 27035254
TI  - High-mobility group box 1 impairs airway epithelial barrier function through the
      activation of the RAGE/ERK pathway.
AB  - Recent studies have indicated that high-mobility group box 1 protein (HMGB1) and
      the receptor for advanced glycation end-products (RAGE) contribute to the
      pathogenesis of asthma. However, whether the activation of the HMGB1/RAGE axis
      mediates airway epithelial barrier dysfunction remains unknown. Thus, the aim of
      this study was to examine the effects of HMGB1 and its synergistic action with
      interleukin (IL)-1beta on airway epithelial barrier properties. We evaluated the
      effects of recombinant human HMGB1 alone or in combination with IL-1beta on ionic
      and macromolecular barrier permeability, by culturing air-liquid interface 16HBE
      cells with HMGB1 to mimic the differentiated epithelium. Western blot analysis
      and immunofluorescence staining were utilized to examine the level and structure
      of major junction proteins, namely E-cadherin, beta-catenin, occludin and claudin
      1. Furthermore, we examined the effects of RAGE neutralizing antibodies and
      mitogen-activated protein kinase (MAPK) inhibitors on epithelial barrier
      properties in order to elucidate the mechanisms involved. HMGB1 increased FITC
      dextran permeability, but suppressed epithelial resistance in a dose- and time
      dependent manner. HMGB1-mediated barrier hyperpermeability was accompanied by a
      disruption of cell-cell contacts, the selective downregulation of occludin and
      claudin-1, and the redistribution of E-cadherin and beta-catenin. HMGB1 in
      synergy with IL-1beta induced a similar, but greater barrier hyperpermeability
      and induced the disruption of junction proteins. Furthermore, HMGB1 elicited the
      activation of the RAGE/extracellular signal-related kinase (ERK)1/2 signaling
      pathway, which correlated with barrier dysfunction in the 16HBE cells. Anti-RAGE
      antibody and the ERK1/2 inhibitor, U0126, attenuated the HMGB1-mediated changes
      in barrier permeability, restored the expression levels of occludin and claudin-1
      and pevented the redistribution of E-cadherin and beta-catenin. Taken together,
      the findings of our study demonstrate that HMGB1 is capable of inducing potent
      effects on epithelial barrier function and that RAGE/ERK1/2 is a key signaling
      pathway involved in the crosstalk between formations of junction proteins and
      epithelial barrier dysfunction.

PMID- 27035255
TI  - Eclipta yellow vein virus enhances chlorophyll destruction, singlet oxygen
      production and alters endogenous redox status in Andrographis paniculata.
AB  - The infection of Eclipta yellow vein virus [EcYVV-IN, Accession No. KC476655],
      recently reported for the first time, on Andrographis paniculata was studied for
      redox-mediated alteration mechanism in infected plants. A. paniculata, an
      important medicinal plant, is used in traditional Indian, Chinese and modern
      system of medicine. Andrographolide, one of the foremost components of this
      plant, is known for its varied pharmacological properties. Our investigation
      provides insight into the effect of virus-induced changes in the singlet oxygen
      quenching due to the alteration in pigment content (chlorophyll and carotenoids)
      as well as activation of plant secondary metabolism along with defense activation
      leading to changes in enzymatic and non-enzymatic redox status. Due to infection,
      a reduction in carotenoid content was observed which leads to reduced quenching
      of singlet oxygen. An increased level of enzymatic (SOD and APX) and non
      enzymatic antioxidant (DPPH, FRAP, RP, NO, TAC and TP) activities were also
      observed in virus-infected plants with a positive correlation (>0.9). However,
      CAT activity was diminished which could be either due to its proteolytic
      degradation or inactivation by superoxide anions (O(2-.)), NO or peroxynitrite
      radicals. A significant (p < 0.05) increase in total phenolic content was
      observed in the infected plants while no considerable difference was seen in the
      total flavonoid content. Our results highlighted the alteration in redox status
      caused by virus-induced biotic stress on the plants and could be useful for
      understanding the after effects of viral infection This study could also be
      helpful in developing biomimetic methods for improving the production of
      secondary metabolites of pharmaceutical importance. 

PMID- 27035256
TI  - Hydrogen sulfide mediates nicotine biosynthesis in tobacco (Nicotiana tabacum)
      under high temperature conditions.
AB  - Hydrogen sulfide (H2S) acts as a signal to induce many physiological processes in
      plants, but its role in controlling the biosynthesis of secondary metabolites is
      not well established. In this study, we found that high temperature (HT)
      treatment induced nicotine biosynthesis in tobacco (Nicotiana tabacum) and
      promoted the rapid accumulation of H2S. Furthermore, HT triggered the
      biosynthesis of jasmonic acid (JA), a plant hormone that promotes nicotine
      biosynthesis. Suppression of the H2S signal using chemical inhibitors or via RNAi
      suppression of l-cysteine desulphydrase (L-CD) in transgenic plants, compromised
      JA production and nicotine biosynthesis under HT treatments, and these inhibitory
      effects could be reversed by applying exogenous H2S. Based on these data, we
      propose that H2S is an important trigger of nicotine biosynthesis in tobacco
      under HT conditions, and that H2S acts upstream of JA signaling by modulating the
      transcription of genes associated with JA biosynthesis. 

PMID- 27035257
TI  - Impact of cluster thinning on transcriptional regulation of anthocyanin
      biosynthesis-related genes in 'Summer Black' grapes.
AB  - Cluster thinning is an agronomic practice that strongly affects anthocyanin
      biosynthesis in the skin of grape berries. However, the impact of cluster
      thinning on anthocyanin biosynthesis has not been fully elucidated at the
      molecular level. Here, we investigated its effects on the berry quality, the
      biosynthesis of anthocyanins, and the expression levels of related genes from the
      onset of veraison to harvest in 'Summer Black' grapes. It was observed that the
      total soluble solid and anthocyanin content in berry skin significantly increased
      under cluster thinning, whereas the berry weight and titratable acidity showed no
      differences from the beginning of veraison to harvest. The expression level of
      most anthocyanin biosynthesis-related genes was significantly up-regulated by
      cluster thinning from the beginning of veraison and was higher at its end
      compared to the control. Up-regulation of flavonoid 3',5'-hydroxylase (F3'5'H)
      and O-methyltransferase (OMT) expression, and down-regulation of flavonoid 3'
      hydroxylase (F3'H) expression were observed, which might be the cause of shift in
      the anthocyanin profile. These findings provide insights into the molecular basis
      of the relationship between cluster thinning and anthocyanin biosynthesis in the
      grape berry skin. 

PMID- 27035258
TI  - Expression analysis of ROS producing and scavenging enzyme-encoding genes in
      rubber tree infected by Pseudocercospora ulei.
AB  - South American Leaf Blight (SALB), caused by the ascomycete Pseudocercospora
      ulei, is responsible for the low productivity of rubber trees in Latin America
      and is a serious threat to rubber plantations in Asia and Africa, where the
      rubber trees are derived from highly susceptible clones. Three contrasted
      genotypes were chosen for their levels of resistance to the pathogen: FX2784
      (totally resistant), MDF180 (partially resistant) and PB314 (susceptible). Array
      analyses were previously performed to identify genes differentially expressed in
      resistant and susceptible genotypes. Twenty-one genes were selected for further
      gene expression analysis in non-inoculated and inoculated genotypes from 24 to
      216 h post infection (hpi). These genes are involved in ROS production (HbRBOHA,
      HbRBOHB, HbRBOHC, HbRBOHD), ROS-scavenging systems (cytoplasmic and chloroplastic
      HbCuZnSOD, HbMnSOD, HbCAT, HbAPX1, HbAPX2, HbMDHAR, HbGCL1, HbGCL2, HbOASTL,
      HbGPX, HbDHAR), and leaf senescence (HbCASP, HbPCYST, HbWRKY2, HbPLY, HbKAT2).
      First, a genotype-dependent level of expression was observed. The genes HbRBOHA,
      HbCuZnSOD cyto, HbCAT, HbGCL and HbWRKY2 were constitutively expressed at lower
      levels in the MDF180 genotype than in the FX2784 and PB314 genotypes. Conversely,
      the levels of expression of HbDHAR, HbGPX and HbPCYST were higher in the older,
      non-inoculated leaves of MDF180. Lower production of ROS and efficient
      regeneration of reduced ascorbate ensure a balanced redox intracellular state in
      this genotype. Second, inoculation of the leaves induced few modifications in the
      expression level of the studied genes. In the MDF180 partially resistant
      genotype, an increase in the expression level of HbRBOHB, HbRBOHD 48 hpi and a
      decrease in the expression level of HbDHAR 216 hpi were observed. In the FX2784
      totally resistant genotype, an increase in the expression level of HbRBOHD and
      HbCuZnSOD cyto and a decrease in HbCAT were observed 48 hpi. This transitory
      variation could be associated with the oxidative burst classically observed in
      hypersensitive response (HR). The increase in the synthesis of reduced
      glutathione in this genotype could ensure redox balance and consequently cell
      homeostasis. In the PB314 susceptible genotype, HbROHC, HbCuZnSOD chloro was up
      regulated 216 hpi concomitantly with a decrease in the expression level of HbCAT,
      consequently causing an accumulation of H2O2 and programmed cell death. The level
      of expression of a transcription factor, HbWRKY2, was also modulated by the P.
      ulei infection with early transient up-regulation in the FX2784 totally resistant
      genotype and permanent up-regulation in the MDF180 partially resistant genotype.
      These results complement studies on genetic determinism of SALB resistance and a
      recent publication on Hevea glutathione reductase gene. 

PMID- 27035260
TI  - A Safer Cigarette? A Comparative Study. A Consensus Report.
AB  - This special issue describes the scientific progress and scientific review
      process to develop a safer cigarette. A peer-review panel, the ECLIPSE Expert
      Panel, was convened to critically review the potential health hazards of this new
      cigarette to a reference, conventional cigarette that bums tobacco. This new
      cigarette is lit and smoked much like other cigarettes, but it burns very little
      tobacco and paper. Also, unlike other cigarettes, it does not burn down to a
      butt, nor does it produce loose ash. Such a product would be expected to have
      less "tar" and other combustion products than cigarettes that burn tobacco and
      should greatly reduce any sidestream smoke. This panel assessed the chemistry and
      physical characteristics, as well as the biological activity, of this new
      cigarette. 

PMID- 27035259
TI  - Using DFT methodology for more reliable predictive models: Design of inhibitors
      of Golgi alpha-Mannosidase II.
AB  - Human Golgi alpha-mannosidase II (GMII), a zinc ion co-factor dependent glycoside
      hydrolase (E.C.3.2.1.114), is a pharmaceutical target for the design of
      inhibitors with anti-cancer activity. The discovery of an effective inhibitor is
      complicated by the fact that all known potent inhibitors of GMII are involved in
      unwanted co-inhibition with lysosomal alpha-mannosidase (LMan, E.C.3.2.1.24), a
      relative to GMII. Routine empirical QSAR models for both GMII and LMan did not
      work with a required accuracy. Therefore, we have developed a fast computational
      protocol to build predictive models combining interaction energy descriptors from
      an empirical docking scoring function (Glide-Schrodinger), Linear Interaction
      Energy (LIE) method, and quantum mechanical density functional theory (QM-DFT)
      calculations. The QSAR models were built and validated with a library of
      structurally diverse GMII and LMan inhibitors and non-active compounds. A
      critical role of QM-DFT descriptors for the more accurate prediction abilities of
      the models is demonstrated. The predictive ability of the models was
      significantly improved when going from the empirical docking scoring function to
      mixed empirical-QM-DFT QSAR models (Q(2)=0.78-0.86 when cross-validation
      procedures were carried out; and R(2)=0.81-0.83 for a testing set). The average
      error for the predicted DeltaGbind decreased to 0.8-1.1kcalmol(-1). Also, 76-80%
      of non-active compounds were successfully filtered out from GMII and LMan
      inhibitors. The QSAR models with the fragmented QM-DFT descriptors may find a
      useful application in structure-based drug design where pure empirical and force
      field methods reached their limits and where quantum mechanics effects are
      critical for ligand-receptor interactions. The optimized models will apply in
      lead optimization processes for GMII drug developments.

PMID- 27035261
TI  - Editorial Preface.

PMID- 27035262
TI  - (1)H NMR study of water molecules confined in nanochannels of mordenite.
AB  - Behavior of water molecules entrapped in nanochannels of zeolite mordenite has
      been investigated by (1)H NMR technique. The (1)H spectra and spin-lattice
      relaxation times in the laboratory and rotating frames, T1 and T1rho,
      respectively, as well as the dipolar relaxation time T1D have been measured in
      the temperature range from 96 to 351K. Diffusion of water molecules along the
      channels was observed above ~200K. While in bulk liquid the dipolar ordered state
      of nuclear spins is not formed owing to complete motional average of dipolar
      interactions, we show that such a state is observed for mobile molecules confined
      in a restricted geometry. At temperatures below ~140K the relaxation was found to
      be mainly caused by interaction of (1)H nuclear spins with paramagnetic
      impurities. Complete lost of the fine structure of (1)H spectra above ~320 K is
      attributed to isotropic molecular reorientation or/and proton exchange. We show
      that the dipolar relaxation in mordenite is responsive to slow 180 degrees 
      reorientations of water molecules. The correlation times of nuclear and electron
      spin fluctuations were determined.

PMID- 27035263
TI  - Response to "Comment on 'Optimal Exposure Biomarkers for Nonpersistent Chemicals
      in Environmental Epidemiology'".

PMID- 27035264
TI  - A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in
      Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced
      Processes.
AB  - We describe a thermodynamic-motivated, information theoretic analysis of
      proteomic data collected from a series of 8 glioblastoma multiforme (GBM) tumors.
      GBMs are considered here as prototypes of heterogeneous cancers. That
      heterogeneity is viewed here as manifesting in different unbalanced biological
      processes that are associated with thermodynamic-like constraints. The analysis
      yields a molecular description of a stable steady state that is common across all
      tumors. It also resolves molecular descriptions of unbalanced processes that are
      shared by several tumors, such as hyperactivated phosphoprotein signaling
      networks. Further, it resolves unbalanced processes that provide unique
      classifiers of tumor subgroups. The results of the theoretical interpretation are
      compared against those of statistical multivariate methods and are shown to
      provide a superior level of resolution for identifying unbalanced processes in
      GBM tumors. The identification of specific constraints for each GBM tumor
      suggests tumor-specific combination therapies that may reverse this imbalance.

PMID- 27035265
TI  - Single-layer MoS2 nanosheet grafted upconversion nanoparticles for near-infrared
      fluorescence imaging-guided deep tissue cancer phototherapy.
AB  - A multifunctional nanostructure is prepared by covalently grafting upconversion
      nanoparticles (UCNPs) with chitosan functionalized MoS2 (MoS2-CS) and folic acid
      (FA) and then loading phthalocyanine (ZnPc) on the surface of MoS2, which
      integrates photodynamic therapy (PDT) with photothermal therapy (PTT) and
      upconversion luminescence imaging into one system for enhanced antitumor
      efficiency. 

PMID- 27035266
TI  - The role of epigenetics in tuberculosis infection.
AB  - Epigenetic mechanisms are pivotal in regulating gene expression during cellular
      response to extracellular stimuli. Bacterial infections have a profound effect on
      the host epigenome, which triggers susceptibility to diseases. Recent studies
      suggest that Mycobacterium tuberculosis (Mtb) can alter the host epigenome to
      modulate the transcriptional machinery and plays a major role in immunomodulation
      of the host immune response. However, the mechanism of epigenetic alterations
      during Mtb infection has not yet been fully understood. Thus, Mtb-induced
      epigenetic changes may affect the host cell by either activation or suppression
      of key immune genes involved in immune response or pathogen persistence. In this
      review, we discuss the principles of epigenetics, recent advances in Mtb-induced
      alterations in the host epigenetic landscape and their role in the host immune
      response. 

PMID- 27035267
TI  - Effectiveness of attachment based STEEPTM intervention in a German high-risk
      sample.
AB  - STEEP(TM) was one of the first attachment-based early intervention programs. The
      program applied findings from the Minnesota Longitudinal Study on Risk and
      Adaptation to the development of a supportive program for young high-risk mothers
      and their infants. STEEP's effectiveness was evaluated first in a randomized
      controlled study launched in 1987. The study showed effects of the one-year
      intervention on important individual and parenting variables, but not on quality
      of mother-infant attachment. In the current German study with young mothers at
      risk for abuse and neglect, a two-year adaptation of STEEP was evaluated within a
      quasi-experimental design. STEEP mother-infant pairs (N = 78) were compared with
      pairs who received standard services of the German Child Welfare System (GCWS, N
      = 29). Compared with GCWS pairs, significantly more mother-infant pairs in the
      intervention group showed secure attachment patterns in Ainsworth's Strange
      Situation when the infants were 12 months of age. At the end of the intervention
      (infant age = 24 month), attachment security scores derived from Waters'
      Attachment Q-Sort were in the predicted direction and showed a medium effect
      size, but did not reach criteria of statistical significance. At both time
      points, the STEEP group showed significantly fewer signs of attachment
      disorganization than the comparison group.

PMID- 27035268
TI  - Phthalates and Childhood Body Fat: Study Finds No Evidence of Obesogenicity.

PMID- 27035269
TI  - Leaky-Wave Radiations by Modulating Surface Impedance on Subwavelength Corrugated
      Metal Structures.
AB  - One-dimensional (1D) subwavelength corrugated metal structures has been described
      to support spoof surface plasmon polaritons (SPPs). Here we demonstrate that a
      periodically modulated 1D subwavelength corrugated metal structure can convert
      spoof SPPs to propagating waves. The structure is fed at the center through a
      slit with a connected waveguide on the input side. The subwavelength corrugated
      metal structure on the output surface is regarded as metasurface and modulated
      periodically to realize the leaky-wave radiation at the broadside. The surface
      impedance of the corrugated metal structure is modulated by using cosine function
      and triangle-wave function, respectively, to reach the radiation effect. Full
      wave simulations and measuremental results are presented to validate the proposed
      design. 

PMID- 27035270
TI  - Periodontal biotype: characteristic, prevalence and dimensions related to dental
      malocclusion.
AB  - BACKGROUND: Knowledge of periodontal anatomy is essential when performing
      surgical and non-surgical procedures in the field of oral healthcare. Gingival
      biotype is often assessed for this purpose. The aim of this study was to assess
      the prevalence of the gingival biotypes in a group of patients and to evaluate if
      the gingival biotypes were related with the different types of Angle's
      classification of malocclusion. METHODS: The study was performed on 76 volunteer
      patients (38 males, 38 females, mean age 14.7 years old). Gingival biotypes were
      assessed with the evaluation on the translucence of a periodontal probe through
      the gingival margin of the tooth during the probing, at the mid facial aspect of
      both maxillary central, lateral incisors and canine; on each patient, Angle's
      classification of malocclusion was also recorded. RESULTS: The prevalence in the
      whole sample of thin gingival biotype was 43.4% and thick gingival biotype was
      56.6%. The frequency of female with thin gingival biotype was significantly less
      respect to male patients (42.4% and 55.6%, respectively) while the thick gingival
      biotype was higher in the female respect to male patients (55.8% and 44.2%,
      respectively) (chi2=1.339, P=0.247). There was not a significant association
      between type of malocclusion and gingival biotype (P=0.143). There was however a
      prevalence of thick gingival biotype in patient with class II malocclusion and a
      slight prevalence of thin gingival biotype in patient with class I malocclusion.
      CONCLUSIONS: No relationship was found between gingival biotypes and Angle's
      classification of malocclusion. In this sample, a higher prevalence of thick
      gingival biotype especially among female subjects was observed.

PMID- 27035271
TI  - A molecular receptor for zwitterionic phenylalanine.
AB  - The combination of a 1,3-ketoenol system and two pyridine molecules attached as
      sulfonamide and carboxamide to a benzofuran skeleton allows the preparation of a
      novel chiral receptor for zwitterionic phenylalanine association. Interestingly,
      no crown-ether, urea or guanidinium are necessary to carry out the extraction of
      amino acids from the aqueous solution, which constitutes a breakthrough in
      comparison with other receptors for zwitterionic amino acid extraction. 

PMID- 27035272
TI  - Correlation of clinical response with homocysteine reduction during therapy with
      reduced B vitamins in patients with MDD who are positive for MTHFR C677T or
      A1298C polymorphism: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: This study was designed to evaluate the efficacy and safety of reduced
      B vitamins as monotherapy in adults with major depressive disorder (MDD) who were
      also positive for at least 1 methylenetetrahydrofolate reductase (MTHFR)
      polymorphism associated with depression and further test the hypothesis that
      reduced (metabolized) B vitamins will lower homocysteine in a majority of
      clinically responding patients. METHODS: 330 adult patients with MDD (DSM-5) and
      positive for either MTHFR C677T or A1298C polymorphism were enrolled in a trial
      conducted between August 1, 2014, and April 3, 2015. 160 patients received
      placebo, while 170 received a capsule containing a combination of reduced B
      vitamins. Plasma homocysteine levels were measured at baseline and week 8. The
      Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate efficacy
      for MDD. RESULTS: 159 of 170 vitamin-treated patients and 123 of 160 placebo
      treated patients were completers. Of the active treatment group, 131 (82.4%)
      showed a reduction in homocysteine (for a mean in this subgroup of 25%, P <
      .001), while 28 (17.6%) showed no significant change. Placebo patients
      demonstrated a small elevation in homocysteine. Active-treatment patients
      demonstrated, on average, a 12-point reduction on the MADRS by week 8, and 42%
      achieved full remission (P < .001). No side effect was significantly different
      between groups. No patients experienced mania. CONCLUSIONS: A combination of
      reduced B vitamins and micronutrients, when used in the treatment of MDD in
      patients with MTHFR polymorphism, resulted in a separation from placebo by week
      2, and 42% of the treatment arm achieved remission by week 8. Further, clinical
      improvement correlated with a significant reduction in homocysteine levels in a
      majority of responders. These results support the homocysteine theory of
      depression and the safety and therapeutic benefit of reduced B vitamins as
      monotherapy for MDD, particularly in patients with MTHFR polymorphism. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT02709668.

PMID- 27035273
TI  - Contaminant dispersion prediction and source estimation with integrated Gaussian
      machine learning network model for point source emission in atmosphere.
AB  - Gas dispersion model is important for predicting the gas concentrations when
      contaminant gas leakage occurs. Intelligent network models such as radial basis
      function (RBF), back propagation (BP) neural network and support vector machine
      (SVM) model can be used for gas dispersion prediction. However, the prediction
      results from these network models with too many inputs based on original
      monitoring parameters are not in good agreement with the experimental data. Then,
      a new series of machine learning algorithms (MLA) models combined classic
      Gaussian model with MLA algorithm has been presented. The prediction results from
      new models are improved greatly. Among these models, Gaussian-SVM model performs
      best and its computation time is close to that of classic Gaussian dispersion
      model. Finally, Gaussian-MLA models were applied to identifying the emission
      source parameters with the particle swarm optimization (PSO) method. The
      estimation performance of PSO with Gaussian-MLA is better than that with
      Gaussian, Lagrangian stochastic (LS) dispersion model and network models based on
      original monitoring parameters. Hence, the new prediction model based on Gaussian
      MLA is potentially a good method to predict contaminant gas dispersion as well as
      a good forward model in emission source parameters identification problem. 

PMID- 27035274
TI  - Transformation of benzophenone-type UV filters by chlorine: Kinetics, products
      identification and toxicity assessments.
AB  - The present study focused on the kinetics, transformation pathways and toxicity
      of several benzophenone-type ultraviolet filters (BPs) during the water
      chlorination disinfection process. The transformation kinetics of the studied
      three BPs was found to be second-order reaction, which was dependent on the
      concentration of BPs and chlorine. The second-order rate constants increased from
      86.7 to 975 M(-1) s(-1) for oxybenzone, 49.6-261.7 M(-1) s(-1) for 4
      hydroxybenzophenone and 51.7-540 M(-1) s(-1) for 2-hydroxy-4-methoxybenzophenone
      5-sulfonic acid with the increasing pH value from 6 to 8 of the chlorination
      disinfection condition. Then the transformation products (TPs) of these BPs were
      identified by HPLC-QTof analysis. Several transformation pathways, including
      electrophilic substitution, methoxyl substitution, ketone groups oxidation,
      hydrolysis, decarboxylation and ring cleavage reaction, were speculated to
      participate in the chlorination transformation process. Finally, according to the
      toxicity experiment on luminescent bacteria, Photobacterium phosphoreum, enhanced
      toxicity was observed for almost all the TPs of the studied BPs except for 2,2'
      dihydroxy-4,4'-dimethoxybenzophenone; it suggested the formation of TPs with more
      toxic than the parent compounds during the chlorination process. The present
      study provided a foundation to understand the transformation of BPs during
      chlorination disinfection process, and was of great significance to the drinking
      water safety.

PMID- 27035275
TI  - Tetramethylpyrazine induces differentiation of human umbilical cord-derived
      mesenchymal stem cells into neuron-like cells in vitro.
AB  - The present study evaluated the ability and optimal concentration of
      tetramethylpyrazine (TMP) to induce human umbilical cord-derived mesenchymal stem
      cells (hUMSCs) to differentiate into neuron-like cells in vitro. Human umbilical
      cords from full-term caesarean section patients were used to obtain hUMSCs by
      collagenase digestion after removal of the umbilical artery and vein. The surface
      antigen expression profile of cultured hUMSCs was monitored by flow cytometry.
      After amplification, cells of the 5th passage were divided into experimental
      groups A-C treated with TMP at 4.67, 2.34 and 1.17 mg/ml, respectively, in low
      glucose-Dulbecco's Modified Eagle's Medium (L-DMEM) (induction medium), while
      group D (control) was exposed to L-DMEM culture medium only. Differentiation of
      hUMSCs into neuron-like cells and morphological changes were observed every 0.5 h
      with an inverted phase contrast microscope for 6 h. After the 6-h induction
      period, proportions of cells expressing neuronal markers neuron-specific enolase
      (NSE), neurofilament protein (NF-H) and glial fibrillary acidic protein (GFAP)
      were detected by immunohistochemistry. The optimal concentration of TMP was
      selected on the basis of neuron-like cell positive rate. Western blotting and RT
      polymerase chain reaction were applied to detect the expression of NSE, NF-H, and
      GFAP of the group of optimal concentration in each point-in-time. Results showed
      that most primary cells were adherent 12 h after seeding and first appeared as
      diamond or polygon shapes. Thereafter, they gradually grew into long spindle
      shaped cells and finally in a radiating or swirling pattern. The cells maintained
      a strong proliferative capacity after continuous passage. Flow cytometry analysis
      of cultured hUMSCs at the 3rd, 5th and 10th passages expressed CD73, CD90 and
      CD105, but not CD11b, CD19, CD34, CD45 or human leukocyte antigen-DR. After 6 h
      of TMP treatment, typical neuron-like cells with many protrusions connected into
      a net-like pattern were observed in all experimental groups. These neuron-like
      cells were positive for NSE and NF-H, but negative for GFAP. Among the tested
      treatment groups, group A with TMP at 4.67 mg/ml had the highest expression of
      NSE and NF-H. By contrast, no change was found after induction in the control
      group. The mRNA expression of cells expressing neuronal markers as well as GAPDH
      was observed, with the relative NSE transcript levels of 0, 1.303+/-0.031,
      1.558+/-0.025, 1.927+/-0.019 and 2.415+/-0.033 after 0, 1, 2, 4 and 6 h of
      treatment, respectively; the mRNA expression of NH-F was 0, 1.429+/-0.025,
      1.551+/-0.024, 1.930+/-0.042 and 1.398+/-0.014 after 0, 1, 2, 4 and 6 h of
      treatment, respectively. There was no expression of GFAP before or after
      induction and all the groups showed high expression of GAPDH at each time point.
      Protein expression was also observed on cells expressing neuronal markers as well
      as GAPDH at each time point. The protein expression of NSE was 0, 0.717+/-0.097,
      0.919+/-0.056, 1.097+/-0.143 and 1.157+/-0.055 in proper order; the protein
      expression of NH-F was 0, 0.780+/-0.103, 0.973+/-0.150, 1.053+/-0.107 and 0.753+/
      0.094 in proper order. There was no expression of GFAP before or after induction,
      and all the groups showed high expression of GAPDH at each tested time point. Our
      results demonstrated that TMP can induce hUMSCs to differentiate into neuron-like
      cells effectively with the optimal concentration of 4.67 mg/ml. After induction,
      the NSE and NF-H of the neuron-like cells were positive, but the GFAP-2 was
      negative. 

PMID- 27035276
TI  - Synthesis and Behavioral Studies of Chiral Cyclopropanes as Selective alpha4beta2
      Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant
      Profile. Part III.
AB  - We report the synthesis and biological characterization of novel derivatives of 3
      [(1-methyl-2(S)-pyrrolidinyl)methoxy]-5-cyclopropylpyridine (4a-f and 5) as
      potent and highly selective alpha4beta2-nicotinic acetylcholine receptor (nAChR)
      full or partial agonists. A systematic structure-activity study was carried out
      on the previously described compound 3b, particularly concerning its (2
      methoxyethyl)cyclopropyl side-chain, in an effort to improve its metabolic
      stability while maintaining receptor selectivity. Compound 4d exhibited very
      similar subnanomolar binding affinity for alpha4beta2- and alpha4beta2*-nAChRs
      compared to 3b, and it showed excellent potency in activating high-sensitivity
      (HS) alpha4beta2-nAChRs with an EC50 value of 8.2 nM. Testing of 4d in the
      SmartCube assay revealed that the compound has a combined antidepressant plus
      antipsychotic signature. In the forced swim test at a dose of 30 mg/kg given
      intraperitoneally, 4d was found to be as efficacious as sertraline, thus
      providing evidence of the potential use of the compound as an antidepressant.
      Additional promise for use of 4d in humans comes from pharmacokinetic studies in
      mice indicating brain penetration, and additional assays show compound stability
      in the presence of human microsomes and hepatocytes. Thus, 4d has a very
      favorable preclinical drug profile.

PMID- 27035277
TI  - How many bound valence states does the C60- anion have?
AB  - We report on unprecedentedly large coupled cluster calculations for the C60(-)
      anion, and on a heuristic model uncovering the valence states of C60(-) that
      allow the resolution of the headlined question. Our results convincingly
      demonstrate that C60(-) possesses as many as four bound valence states: (2)T1u,
      (2)T1g, (2)T2u and (2)Hg. Our findings reconcile previous controversies regarding
      the existence of the bound (2)T2u and (2)Hg states. For all bound states of C60(
      ) we present an analysis of the radial and angular distributions of the excess
      electron, which reveals some unique properties of the valence states. Some
      interesting features of the introduced model are analyzed and discussed. 

PMID- 27035278
TI  - MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting
      ARID2.
AB  - Aberrant expression of microRNA-155 (miR-155) has been reported in several human
      cancers and is associated with prognosis of patients. However, the clinical
      significance of miR-155 and its underlying mechanisms involved in
      hepatocarcinogenesis remain to be determined. In this study, we demonstrated that
      the expression of miR-155 was elevated in both hepatocellular carcinoma (HCC)
      tissues and cell lines. Clinical association analysis revealed that high
      expression of miR-155 was correlated with malignant clinicopathological
      characteristics including large tumor size, high Edmondson-Steiner grading and
      TNM tumor stage. Furthermore, its high expression conferred a reduced 5-year
      overall survival and disease-free survival of HCC patients. Gain- and loss-of
      function studies revealed that miR-155 promoted cell cycle progression, cell
      proliferation and inhibited apoptosis. Mechanistically, we identified AT-rich
      interactive domain 2 (ARID2) as a direct downstream target and functional
      mediator of miR-155 in HCC cells. Notably, alterations of ARID2 expression
      abrogated the effects of miR-155 on HCC cell proliferation, cell cycle and
      apoptosis. Moreover, we demonstrated that Akt phosphorylation is essential for
      the functional roles of miR-155 through altering Cyclin D1 and p27, which were
      key components of cell cycle machinery. Finally, we disclosed that the
      downregulation of miR-155 suppressed tumor growth of HCC by inhibiting Akt
      signaling pathway. In conclusion, our results indicate that miR-155 promotes
      tumor growth of HCC by targeting ARID2-mediated Akt phosphorylation pathway, and
      potentially serves as a novel prognostic biomarker and therapeutic target for
      HCC. 

PMID- 27035279
TI  - Macromolecular Brushes as Stabilizers of Hydrophobic Solute Nanoparticles.
AB  - Macromolecular brushes bearing poly(ethylene glycol) and poly(d,l-lactide) side
      chains were used to stabilize hydrophobic solute nanoparticles formed by a rapid
      change in solvent quality. Unlike linear diblock copolymers with the same
      hydrophilic and hydrophobic block chemistries, the brush copolymer enabled the
      formation of ellipsoidal beta-carotene nanoparticles, which in cosolvent mixtures
      developed into rod-like structures, resulting from a combination of Ostwald
      ripening and particle aggregation. The stabilizing ability of the copolymer was
      highly dependent on the mobility of the hydrophobic component, influenced by its
      molecular weight. As shown here, asymmetric amphiphilic macromolecular brushes of
      this type may be used as hydrophobic drug stabilizers and potentially assist the
      shape control of nonspherical aggregate morphologies.

PMID- 27035280
TI  - Bilirubin concentration correlates with positive symptoms in patients with
      schizophrenia.
AB  - OBJECTIVE: Besides its toxic effects, bilirubin has been demonstrated to have
      antioxidant properties to counteract oxidative stress, which has been suggested
      to play a role in the pathophysiology of schizophrenia. METHODS: This study
      investigated the potential association between changes in psychopathology
      measured by the Lindenmayer model of the Positive and Negative Syndrome Scale
      (PANSS) and changes in total plasma bilirubin concentrations. Data of patients
      with schizophrenia (ICD-10) starting monotherapy with a new-generation
      antipsychotic were analyzed at baseline (N = 52) and 2 (n = 40), 4 (n = 46), and
      12 weeks (n = 30) after the initiation of treatment. Data were collected between
      December 1997 and October 2007 and analyzed retrospectively. RESULTS: The PANSS
      total score decreased significantly from baseline to weeks 2, 4, and 12 of
      treatment (all P values <= .001). Total plasma bilirubin concentration also
      dropped significantly from baseline to week 2 (P = .015) and decreased further
      until week 4 (P = .013); no significant decrease was observed between baseline
      and week 12. Spearman rank correlation revealed a significant association of
      bilirubin concentration with the PANSS positive (r = 0.371, P = .007) and
      excitement (r = 0.322, P = .020) components at baseline. No further correlations
      were found. From baseline to weeks 2, 4, and 12, changes in the PANSS positive
      component correlated significantly with changes in plasma bilirubin concentration
      (all P values < .05), whereas correlations between changes in the remaining PANSS
      components and bilirubin were less consistent. CONCLUSIONS: Assuming that
      positive symptoms are associated with the subjective experience of psychological
      distress, our findings indirectly expand the evidence on potential antioxidant
      properties of bilirubin in patients with schizophrenia.

PMID- 27035281
TI  - Noble Hybrid Nanostructures as Efficient Anti-Proliferative Platforms for Human
      Breast Cancer Cell.
AB  - Nanomaterials have proven to possess great potential in biomaterials research.
      Recently, they have suggested considerable promise in cancer diagnosis and
      therapy. Among others, silicon (Si) nanomaterials have been extensively employed
      for various biomedical applications; however, the utilization of Si for cancer
      therapy has been limited to nanoparticles, and its potential as anticancer
      substrates has not been fully explored. Noble nanoparticles have also received
      considerable attention owing to unique anticancer properties to improve the
      efficiency of biomaterials for numerous biological applications. Nevertheless,
      immobilization and control over delivery of the nanoparticles have been
      challenge. Here, we develop hybrid nanoplatforms to efficiently hamper breast
      cancer cell adhesion and proliferation. Platforms are synthesized by femtosecond
      laser processing of Si into multiphase nanostructures, followed by sputter
      coating with gold (Au)/gold-palladium (Au-Pd) nanoparticles. The performance of
      the developed platforms was then examined by exploring the response of normal
      fibroblast and metastatic breast cancer cells. Our results from the quantitative
      and qualitative analyses show a dramatic decrease in the number of breast cancer
      cells on the hybrid platform compared to untreated substrates. Whereas,
      fibroblast cells form stable adhesion with stretched and elongated cytoskeleton
      and actin filaments. The hybrid platforms perform as dual-acting
      cytophobic/cytostatic stages where Si nanostructures depress breast cancer cell
      adhesion while immobilized Au/Au-Pd nanoparticles are gradually released to
      affect any surviving cell on the nanostructures. The nanoparticles are believed
      to be taken up by breast cancer cells via endocytosis, which subsequently alter
      the cell nucleus and may cause cell death. The findings suggest that the density
      of nanostructures and concentration of coated nanoparticles play critical roles
      on cytophobic/cytostatic properties of the platforms on human breast cancer cells
      while having no or even cytophilic effects on fibroblast cells. Because of the
      remarkable contrary responses of normal and cancer cells to the proposed
      platform, we envision that it will provide novel applications in cancer research.

PMID- 27035282
TI  - Anticancer effect of docetaxel induces apoptosis of prostate cancer via the
      cofilin-1 and paxillin signaling pathway.
AB  - Prostate cancer is a common multiple malignant tumor occurring in males. Prostate
      cancer mortality is the 2nd most common of all tumor types in Western countries
      and the mortality of morbidity is 13% in the USA. The present study aimed to
      investigate the anticancer effect of docetaxel on inducing the apoptosis of
      prostate cancer via the cofilin-1 and paxillin signaling pathway. Treatment with
      docetaxel (1-50 nM) disposed the human LNCaP prostate cancer cells for 24 h. Cell
      growth and cytotoxicity were subsequently measured using a 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase assay,
      respectively. Docetaxel-induced cell death was analyzed using flow cytometric and
      caspase-3 assays. Reverse transcription-quantitative polymerase chain reaction
      analysis was used to detect the gene expression of cofilin-1 and western blots
      were used to determine the protein expression of paxillin. Treatment with
      docetaxel inhibited cell growth, promoted cytotoxicity, activated apoptosis and
      increased caspase-3 activity in the LNCaP cells. Notably, administration of
      docetaxel reduced the gene expression of cofilin-1 and the protein expression of
      paxillin in the LNCaP cells. Additionally, knockdown of cofilin-1 advanced the
      anticancer effect of docetaxel against LNCaP cells through suppression of the
      paxillin pathway. The present findings demonstrated that the anticancer effect of
      docetaxel induces the apoptosis of prostate cancer via the suppression of the
      cofilin-1 and paxillin signaling pathways, which will assist in setting a stage
      for the clinical treatment of prostate cancer. 

PMID- 27035283
TI  - n-3 polyunsaturated fatty acids abrogate mTORC1/2 signaling and inhibit
      adrenocortical carcinoma growth in vitro and in vivo.
AB  - n-3 polyunsaturated fatty acids (PUFAs) are essential for human health and have
      been reported to reduce the risk of cancer, inhibit the growth of various types
      of tumors both in vitro and in vivo, and affect adrenal function. However, their
      effects on adrenocortical carcinoma (ACC) are not known. In the present study, we
      demonstrated that docosahexenoic acid (DHA) inhibited ACC cell proliferation,
      colony formation and cell cycle progression, and promoted apoptosis. In addition,
      ectopic expression of fat-1, a desaturase that converts n-6 to n-3 PUFAs
      endogenously, also inhibited ACC cell proliferation. Moreover, supplementing n-3
      PUFAs in the diet efficiently prevented ACC cell growth in xenograft models.
      Notably, implanted ACC cells were unable to grow in fat-1 transgenic severe
      combined immune deficiency mice. Further study revealed that exogenous and
      endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and
      mTORC2 signaling in ACC in vitro and in vivo. Taken together, our findings
      provide comprehensive preclinical evidence that n-3 PUFAs efficiently prevent ACC
      growth by inhibiting mTORC1/2, which may have important implications in the
      treatment of ACC. 

PMID- 27035284
TI  - Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell
      Carcinoma Occurrence and Development.
AB  - A number of genetic variants have been associated with cancer occurrence, however
      it may be the acquired somatic mutations (SMs) that drive cancer development.
      This study investigates the potential SMs and related genetic variants associated
      with the occurrence and development of head and neck squamous cell carcinoma
      (HNSCC). We identified several SMs in NOTCH1 from whole-exome sequencing and
      validated them in a 13-year cohort of 128 HNSCC patients using a high-resolution
      melting analysis and resequencing. Patients who have NOTCH1 SMs show higher 5
      year relapse-free recurrence (P = 0.0013) and lower survival proportion (P =
      0.0447) when the risk-associated SMs were analysed by Cox proportional hazard
      models. Interestingly, the NOTCH1 gene rs139994842 that shares linkage with SMs
      is associated with HNSCC risk (OR = 3.46), increasing when SMs in NOTCH1 are
      involved (OR = 7.74), and furthermore when there are SMs in conjunction to betel
      quid chewing (OR = 32.11), which is a related independent environmental risk
      factor after adjusting for substances use (alcohol, betel quid, cigarettes) and
      age. The findings indicate that betel quid chewing is highly associated with
      NOTCH1 SMs (especially with changes in EGF-like domains), and that rs139994842
      may potentially serve as an early predictive and prognostic biomarker for the
      occurrence and development of HNSCC.

PMID- 27035285
TI  - Gold(I)-Catalyzed Cascade Hydroarylation/Cycloaromatization to Indolizines via
      Pyridine Ring Construction.
AB  - An efficient and atom-economic method for the synthesis of multisubstituted
      indolizines via gold-catalyzed cascade hydroarylation/cycloaromatization reaction
      of alpha-(N-pyrrolyl)ketones with alkynes is described. The reaction is realized
      through the construction of the pyridine ring of indolizines, which allows the
      regioselective incorporation of a wide range of functionalities on the pyridine
      unit.

PMID- 27035286
TI  - FeB6 Monolayers: The Graphene-like Material with Hypercoordinate Transition
      Metal.
AB  - By means of density functional theory (DFT) computations and global minimum
      search using particle-swarm optimization (PSO) method, we predicted three FeB6
      monolayers, namely alpha-FeB6, beta-FeB6 and gamma-FeB6, which consist of the
      Fe(c)Bx (x = 6, 8) wheels with planar hypercoordinate Fe atoms locating at the
      center of six- or eight-membered boron rings. In particular, the alpha-FeB6 sheet
      constructed by Fe(c)B8 motifs is the global minimum due to completely shared and
      well delocalized electrons. The two-dimensional (2D) boron networks are
      dramatically stabilized by the electron transfer from Fe atoms, and the FeB6
      monolayers have pronounced stabilities. The alpha-FeB6 monolayer is metallic,
      while the beta-FeB6 and gamma-FeB6 sheets are semiconductors with indirect band
      gaps and significant visible-light absorptions. Besides the novel chemical
      bonding, the high feasibility for experimental realization, and unique electronic
      and optical properties, render them very welcome new members to the graphene-like
      materials family.

PMID- 27035287
TI  - Maternal undernutrition leads to elevated hepatic triglycerides in male rat
      offspring due to increased expression of lipoprotein lipase.
AB  - Small for gestational age (SGA) at birth increases the risk of developing
      metabolic syndrome, which encompasses various symptoms including
      hypertriglyceridemia. The aim of the present study was to determine whether
      maternal undernutrition during pregnancy may lead to alterations in hepatic
      triglyceride content and the gene expression levels of hepatic lipoprotein lipase
      (LPL) in SGA male offspring. The present study focused on the male offspring in
      order to prevent confounding factors, such as estrus cycle and hormone profile.
      Female Sprague Dawley rats were arbitrarily assigned to receive an ad libitum
      chow diet or 50% food restricted diet from pregnancy day 1 until parturition.
      Reverse transcription quantitative polymerase chain reaction and western blot
      analysis were used to measure the gene expression levels of hepatic LPL at day 1
      and upon completion of the third week of age. Chromatin immunoprecipitation
      quantified the binding activity of liver X receptor-alpha (LXR-alpha) gene to the
      LXR response elements (LXRE) on LPL promoter and LPL epigenetic characteristics.
      At 3 weeks of age, SGA male offspring exhibited significantly elevated levels of
      hepatic triglycerides, which was concomitant with increased expression levels of
      LPL. Since LPL is regulated by LXR-alpha, the expression levels of LXR-alpha were
      detected in appropriate for gestational age and SGA male offspring. Maternal
      undernutrition during pregnancy led to an increase in the hepatic expression
      levels of LXR-alpha, and enriched binding to the putative LXR response elements
      in the LPL promoter regions in 3-week-old male offspring. In addition, enhanced
      acetylation of histone H3 [H3 lysine (K)9 and H3K14] was detected surrounding the
      LPL promoter. The results of the present study indicated that maternal
      undernutrition during pregnancy may lead to an increase in hepatic triglycerides,
      via alterations in the transcriptional and epigenetic regulation of the LPL gene.

PMID- 27035288
TI  - Correlations of the Time Dependent Signal and the State of a Continuously
      Monitored Quantum System.
AB  - In quantum physics, measurements give random results and yield a corresponding
      random backaction on the state of the system subject to measurement. If a quantum
      system is probed continuously over time, its state evolves along a stochastic
      quantum trajectory. To investigate the characteristic properties of such
      dynamics, we perform weak continuous measurements on a superconducting qubit that
      is driven to undergo Rabi oscillations. From the data we observe a number of
      striking temporal correlations within the time dependent signals and the quantum
      trajectories of the qubit, and we discuss their explanation in terms of quantum
      measurement and photodetection theory. 

PMID- 27035289
TI  - Reduced Sensitivity to Charge Noise in Semiconductor Spin Qubits via Symmetric
      Operation.
AB  - We demonstrate improved operation of exchange-coupled semiconductor quantum dots
      by substantially reducing the sensitivity of exchange operations to charge noise.
      The method involves biasing a double dot symmetrically between the charge-state
      anticrossings, where the derivative of the exchange energy with respect to gate
      voltages is minimized. Exchange remains highly tunable by adjusting the tunnel
      coupling. We find that this method reduces the dephasing effect of charge noise
      by more than a factor of 5 in comparison to operation near a charge-state
      anticrossing, increasing the number of observable exchange oscillations in our
      qubit by a similar factor. Performance also improves with exchange rate, favoring
      fast quantum operations. 

PMID- 27035290
TI  - Creating a Superposition of Unknown Quantum States.
AB  - The superposition principle is one of the landmarks of quantum mechanics. The
      importance of quantum superpositions provokes questions about the limitations
      that quantum mechanics itself imposes on the possibility of their generation. In
      this work, we systematically study the problem of the creation of superpositions
      of unknown quantum states. First, we prove a no-go theorem that forbids the
      existence of a universal probabilistic quantum protocol producing a superposition
      of two unknown quantum states. Second, we provide an explicit probabilistic
      protocol generating a superposition of two unknown states, each having a fixed
      overlap with the known referential pure state. The protocol can be applied to
      generate coherent superposition of results of independent runs of subroutines in
      a quantum computer. Moreover, in the context of quantum optics it can be used to
      efficiently generate highly nonclassical states or non-Gaussian states. 

PMID- 27035291
TI  - Weak Values from Displacement Currents in Multiterminal Electron Devices.
AB  - Weak values allow the measurement of observables associated with noncommuting
      operators. Up to now, position-momentum weak values have been mainly developed
      for (relativistic) photons. In this Letter, a proposal for the measurement of
      such weak values in typical electronic devices is presented. Inspired by the Ramo
      Shockley-Pellegrini theorem that provides a relation between current and electron
      velocity, it is shown that the displacement current measured in multiterminal
      configurations can provide either a weak measurement of the momentum or strong
      measurement of position. This proposal opens new opportunities for fundamental
      and applied physics with state-of-the-art electronic technology. As an example, a
      setup for the measurement of the Bohmian velocity of (nonrelativistic) electrons
      is presented and tested with numerical experiments. 

PMID- 27035292
TI  - Universal Continuous-Variable State Orthogonalizer and Qubit Generator.
AB  - We experimentally demonstrate a universal strategy for producing a quantum state
      that is orthogonal to an arbitrary, infinite-dimensional, pure input one, even if
      only a limited amount of information about the latter is available. Arbitrary
      coherent superpositions of the two mutually orthogonal states are then produced
      by a simple change in the experimental parameters. We use input coherent states
      of light to illustrate two variations of the method. However, we show that the
      scheme works equally well for arbitrary input fields and constitutes a universal
      procedure, which may thus prove a useful building block for quantum state
      engineering and quantum information processing with continuous-variable qubits. 

PMID- 27035293
TI  - Theory of Casimir Forces without the Proximity-Force Approximation.
AB  - We analyze both the attractive and repulsive Casimir-Lifshitz forces recently
      reported in experimental investigations. By using a kinetic approach, we obtain
      the Casimir forces from the power absorbed by the materials. We consider
      collective material excitations through a set of relaxation times distributed in
      frequency according to a log-normal function. A generalized expression for these
      forces for arbitrary values of temperature is obtained. We compare our results
      with experimental measurements and conclude that the model goes beyond the
      proximity-force approximation. 

PMID- 27035294
TI  - Unitary Limit of Two-Nucleon Interactions in Strong Magnetic Fields.
AB  - Two-nucleon systems are shown to exhibit large scattering lengths in strong
      magnetic fields at unphysical quark masses, and the trends toward the physical
      values indicate that such features may exist in nature. Lattice QCD calculations
      of the energies of one and two nucleons systems are performed at pion masses of
      m_{pi}~450 and 806 MeV in uniform, time-independent magnetic fields of strength
      |B|~10^{19}-10^{20}  G to determine the response of these hadronic systems to
      large magnetic fields. Fields of this strength may exist inside magnetars and in
      peripheral relativistic heavy ion collisions, and the unitary behavior at large
      scattering lengths may have important consequences for these systems. 

PMID- 27035297
TI  - Large-Scale Shell-Model Analysis of the Neutrinoless betabeta Decay of ^{48}Ca.
AB  - We present the nuclear matrix element for the neutrinoless double-beta decay of
      ^{48}Ca based on large-scale shell-model calculations including two harmonic
      oscillator shells (sd and pf shells). The excitation spectra of ^{48}Ca and
      ^{48}Ti, and the two-neutrino double-beta decay of ^{48}Ca are reproduced in good
      agreement to the experimental data. We find that the neutrinoless double-beta
      decay nuclear matrix element is enhanced by about 30% compared to pf-shell
      calculations. This reduces the decay lifetime by almost a factor of 2. The matrix
      element increase is mostly due to pairing correlations associated with cross
      shell sd-pf excitations. We also investigate possible implications for heavier
      neutrinoless double-beta decay candidates. 

PMID- 27035296
TI  - Evidence for Octupole Correlations in Multiple Chiral Doublet Bands.
AB  - Two pairs of positive-and negative-parity doublet bands together with eight
      strong electric dipole transitions linking their yrast positive- and negative
      parity bands have been identified in ^{78}Br. They are interpreted as multiple
      chiral doublet bands with octupole correlations, which is supported by the
      microscopic multidimensionally-constrained covariant density functional theory
      and triaxial particle rotor model calculations. This observation reports the
      first example of chiral geometry in octupole soft nuclei. 

PMID- 27035298
TI  - Direct Evidence of Octupole Deformation in Neutron-Rich ^{144}Ba.
AB  - The neutron-rich nucleus ^{144}Ba (t_{1/2}=11.5  s) is expected to exhibit some
      of the strongest octupole correlations among nuclei with mass numbers A less than
      200. Until now, indirect evidence for such strong correlations has been inferred
      from observations such as enhanced E1 transitions and interleaving positive- and
      negative-parity levels in the ground-state band. In this experiment, the octupole
      strength was measured directly by sub-barrier, multistep Coulomb excitation of a
      post-accelerated 650-MeV ^{144}Ba beam on a 1.0-mg/cm^{2} ^{208}Pb target. The
      measured value of the matrix element, ?3_{1}^{-}?M(E3)?0_{1}^{+}?=0.65(+17/-23)
      eb^{3/2}, corresponds to a reduced B(E3) transition probability of 48(+25/-34) 
      W.u. This result represents an unambiguous determination of the octupole
      collectivity, is larger than any available theoretical prediction, and is
      consistent with octupole deformation. 

PMID- 27035299
TI  - Anomalous Broadening in Driven Dissipative Rydberg Systems.
AB  - We observe interaction-induced broadening of the two-photon 5s-18s transition in
      ^{87}Rb atoms trapped in a 3D optical lattice. The measured linewidth increases
      by nearly 2 orders of magnitude with increasing atomic density and excitation
      strength, with corresponding suppression of resonant scattering and enhancement
      of off-resonant scattering. We attribute the increased linewidth to resonant
      dipole-dipole interactions of 18s atoms with blackbody induced population in
      nearby np states. Over a range of initial atomic densities and excitation
      strengths, the transition width is described by a single function of the steady
      state density of Rydberg atoms, and the observed resonant excitation rate
      corresponds to that of a two-level system with the measured, rather than natural,
      linewidth. The broadening mechanism observed here is likely to have negative
      implications for many proposals with coherently interacting Rydberg atoms. 

PMID- 27035300
TI  - Photodissociation of an Internally Cold Beam of CH^{+} Ions in a Cryogenic
      Storage Ring.
AB  - We have studied the photodissociation of CH^{+} in the Cryogenic Storage Ring at
      ambient temperatures below 10 K. Owing to the extremely high vacuum of the
      cryogenic environment, we were able to store CH^{+} beams with a kinetic energy
      of ~60  keV for several minutes. Using a pulsed laser, we observed Feshbach-type
      near-threshold photodissociation resonances for the rotational levels J=0-2 of
      CH^{+}, exclusively. In comparison to updated, state-of-the-art calculations, we
      find excellent agreement in the relative intensities of the resonances for a
      given J, and we can extract time-dependent level populations. Thus, we can
      monitor the spontaneous relaxation of CH^{+} to its lowest rotational states and
      demonstrate the preparation of an internally cold beam of molecular ions. 

PMID- 27035301
TI  - Low Temperature Kinetics of the First Steps of Water Cluster Formation.
AB  - We present a combined experimental and theoretical low temperature kinetic study
      of water cluster formation. Water cluster growth takes place in low temperature
      (23-69 K) supersonic flows. The observed kinetics of formation of water clusters
      are reproduced with a kinetic model based on theoretical predictions for the
      first steps of clusterization. The temperature- and pressure-dependent
      association and dissociation rate coefficients are predicted with an ab initio
      transition state theory based master equation approach over a wide range of
      temperatures (20-100 K) and pressures (10^{-6}-10  bar). 

PMID- 27035302
TI  - Ground State Electroluminescence.
AB  - Electroluminescence, the emission of light in the presence of an electric
      current, provides information on the allowed electronic transitions of a given
      system. It is commonly used to investigate the physics of strongly coupled light
      matter systems, whose eigenfrequencies are split by the strong coupling with the
      photonic field of a cavity. Here we show that, together with the usual
      electroluminescence, systems in the ultrastrong light-matter coupling regime emit
      a uniquely quantum radiation when a flow of current is driven through them. While
      standard electroluminescence relies on the population of excited states followed
      by spontaneous emission, the process we describe herein extracts bound photons
      from the dressed ground state and it has peculiar features that unequivocally
      distinguish it from usual electroluminescence. 

PMID- 27035303
TI  - Tweezers for Chimeras in Small Networks.
AB  - We propose a control scheme which can stabilize and fix the position of chimera
      states in small networks. Chimeras consist of coexisting domains of spatially
      coherent and incoherent dynamics in systems of nonlocally coupled identical
      oscillators. Chimera states are generally difficult to observe in small networks
      due to their short lifetime and erratic drifting of the spatial position of the
      incoherent domain. The control scheme, like a tweezer, might be useful in
      experiments, where usually only small networks can be realized. 

PMID- 27035295
TI  - Beam Energy Dependence of the Third Harmonic of Azimuthal Correlations in Au+Au
      Collisions at RHIC.
AB  - We present results from a harmonic decomposition of two-particle azimuthal
      correlations measured with the STAR detector in Au+Au collisions for energies
      ranging from sqrt[s_{NN}]=7.7 to 200 GeV. The third harmonic
      v_{3}^{2}{2}=?cos3(phi_{1}-phi_{2})?, where phi_{1}-phi_{2} is the angular
      difference in azimuth, is studied as a function of the pseudorapidity difference
      between particle pairs Deltaeta=eta_{1}-eta_{2}. Nonzero v_{3}^{2}{2} is directly
      related to the previously observed large-Deltaeta narrow-Deltaphi ridge
      correlations and has been shown in models to be sensitive to the existence of a
      low viscosity quark gluon plasma phase. For sufficiently central collisions,
      v_{3}^{2}{2} persist down to an energy of 7.7 GeV, suggesting that quark gluon
      plasma may be created even in these low energy collisions. In peripheral
      collisions at these low energies, however, v_{3}^{2}{2} is consistent with zero.
      When scaled by the pseudorapidity density of charged-particle multiplicity per
      participating nucleon pair, v_{3}^{2}{2} for central collisions shows a minimum
      near sqrt[s_{NN}]=20  GeV. 

PMID- 27035304
TI  - Bright X-Ray Source from a Laser-Driven Microplasma Waveguide.
AB  - Owing to the rapid progress in laser technology, very high-contrast femtosecond
      laser pulses of relativistic intensities have become available. These pulses
      allow for interaction with microstructured solid-density plasma without
      destroying the structure by parasitic prepulses. This opens a new realm of
      possibilities for laser interaction with micro- and nanoscale photonic materials
      at relativistic intensities. Here we demonstrate, for the first time, that when
      coupled with a readily available 1.8 J laser, a microplasma waveguide (MPW) may
      serve as a novel compact x-ray source. Electrons are extracted from the walls and
      form a dense helical bunch inside the channel. These electrons are efficiently
      accelerated and wiggled by the waveguide modes in the MPW, which results in a
      bright, well-collimated emission of hard x rays in the range of 1~100  keV. 

PMID- 27035305
TI  - Phase Separation of Binary Charged Particle Systems with Small Size Disparities
      using a Dusty Plasma.
AB  - The phase separation in binary mixtures of charged particles has been
      investigated in a dusty plasma under microgravity on parabolic flights. A method
      based on the use of fluorescent dust particles was developed that allows us to
      distinguish between particles of slightly different size. A clear trend towards
      phase separation even for smallest size (charge) disparities is observed. The
      diffusion flux is directly measured from the experiment and uphill diffusion
      coefficients have been determined. 

PMID- 27035306
TI  - Unified Concept of Effective One Component Plasma for Hot Dense Plasmas.
AB  - Orbital-free molecular dynamics simulations are used to benchmark two popular
      models for hot dense plasmas: the one component plasma (OCP) and the Yukawa
      model. A unified concept emerges where an effective OCP (EOCP) is constructed
      from the short-range structure of the plasma. An unambiguous ionization and the
      screening length can be defined and used for a Yukawa system, which reproduces
      the long-range structure with finite compressibility. Similarly, the dispersion
      relation of longitudinal waves is consistent with the screened model at vanishing
      wave number but merges with the OCP at high wave number. Additionally, the EOCP
      reproduces the overall relaxation time scales of the correlation functions
      associated with ionic motion. In the hot dense regime, this unified concept of
      EOCP can be fruitfully applied to deduce properties such as the equation of
      state, ionic transport coefficients, and the ion feature in x-ray Thomson
      scattering experiments. 

PMID- 27035307
TI  - X-ray Thomson Scattering in Warm Dense Matter without the Chihara Decomposition.
AB  - X-ray Thomson scattering is an important experimental technique used to measure
      the temperature, ionization state, structure, and density of warm dense matter
      (WDM). The fundamental property probed in these experiments is the electronic
      dynamic structure factor. In most models, this is decomposed into three terms [J.
      Chihara, J. Phys. F 17, 295 (1987)] representing the response of tightly bound,
      loosely bound, and free electrons. Accompanying this decomposition is the
      classification of electrons as either bound or free, which is useful for gapped
      and cold systems but becomes increasingly questionable as temperatures and
      pressures increase into the WDM regime. In this work we provide unambiguous first
      principles calculations of the dynamic structure factor of warm dense beryllium,
      independent of the Chihara form, by treating bound and free states under a single
      formalism. The computational approach is real-time finite-temperature time
      dependent density functional theory (TDDFT) being applied here for the first time
      to WDM. We compare results from TDDFT to Chihara-based calculations for
      experimentally relevant conditions in shock-compressed beryllium. 

PMID- 27035308
TI  - Model-Independent Determination of the Shear Viscosity of a Trapped Unitary Fermi
      gas: Application to High-Temperature Data.
AB  - Determinations of the shear viscosity of trapped ultracold gases suffer from
      systematic, uncontrolled uncertainties related to the treatment of the dilute
      part of the gas cloud. In this work we present an analysis of expansion
      experiments based on a new method, anisotropic fluid dynamics, that interpolates
      between Navier-Stokes fluid dynamics at the center of the cloud and ballistic
      behavior in the dilute corona. We validate the method using a comparison between
      anisotropic fluid dynamics and numerical solutions of the Boltzmann equation. We
      then apply anisotropic fluid dynamics to the expansion data reported by Cao et
      al. In the high-temperature limit we find eta=0.282(mT)^{3/2}, which agrees
      within about 5% with the theoretical prediction eta=0.269(mT)^{3/2}. 

PMID- 27035309
TI  - Decoupling Nonclassical Nonlinear Behavior of Elastic Wave Types.
AB  - In this Letter, the tensorial nature of the nonequilibrium dynamics in nonlinear
      mesoscopic elastic materials is evidenced via multimode resonance experiments. In
      these experiments the dynamic response, including the spatial variations of
      velocities and strains, is carefully monitored while the sample is vibrated in a
      purely longitudinal or a purely torsional mode. By analogy with the fact that
      such experiments can decouple the elements of the linear elastic tensor, we
      demonstrate that the parameters quantifying the nonequilibrium dynamics of the
      material differ substantially for a compressional wave and for a shear wave. This
      result could lead to further understanding of the nonlinear mechanical phenomena
      that arise in natural systems as well as to the design and engineering of
      nonlinear acoustic metamaterials. 

PMID- 27035310
TI  - Role of Fourier Modes in Finite-Size Scaling above the Upper Critical Dimension.
AB  - Renormalization-group theory has stood, for over 40 years, as one of the pillars
      of modern physics. As such, there should be no remaining doubt regarding its
      validity. However, finite-size scaling, which derives from it, has long been
      poorly understood above the upper critical dimension d_{c} in models with free
      boundary conditions. In addition to its fundamental significance for scaling
      theories, the issue is important at a practical level because finite-size,
      statistical-physics systems with free boundaries and above d_{c} are
      experimentally relevant for long-range interactions. Here, we address the roles
      played by Fourier modes for such systems and show that the current
      phenomenological picture is not supported for all thermodynamic observables with
      either free or periodic boundaries. In particular, the expectation that dangerous
      irrelevant variables cause Gaussian-fixed-point scaling indices to be replaced by
      Landau mean-field exponents for all Fourier modes is incorrect. Instead, the
      Gaussian-fixed-point exponents have a direct physical manifestation for some
      modes above the upper critical dimension. 

PMID- 27035311
TI  - Coherent Chromatic Effect in the Transmission Electron Microscope.
AB  - Under the assumption of local atomic scattering, elastic electron scattering at
      finite scattering angles implies a small but finite energy loss. This energy
      loss, which under conventional imaging conditions in high-resolution transmission
      electron microscopy is of the order of 0.1 meV and thus negligible, increases by
      more than 2 orders of magnitude if light elements are investigated at sub
      Angstrom resolution. For a microscope of finite chromatic aberration, the energy
      loss leads to an element-specific chromatic effect which increases with the
      instrument resolution and with decreasing mass of the scattering atom. Despite
      that this effect is small, it can degrade the achievable image contrast. However,
      the effect can be considered in the optimization of the phase-contrast imaging
      conditions and even be beneficial to enhance the relative image contrast of light
      atoms in the presence of heavy atoms. 

PMID- 27035312
TI  - Electronic Structure of YbB_{6}: Is it a Topological Insulator or Not?
AB  - To finally resolve the controversial issue of whether or not the electronic
      structure of YbB_{6} is nontrivially topological, we have made a combined study
      using angle-resolved photoemission spectroscopy (ARPES) of the nonpolar (110)
      surface and density functional theory (DFT). The flat-band conditions of the
      (110) ARPES avoid the strong band bending effects of the polar (001) surface and
      definitively show that YbB_{6} has a topologically trivial B 2p-Yb 5d
      semiconductor band gap of ~0.3  eV. Accurate determination of the low energy band
      topology in DFT requires the use of a modified Becke-Johnson exchange potential
      incorporating spin-orbit coupling and an on-site Yb 4f Coulomb interaction U as
      large as 7 eV. The DFT result, confirmed by a more precise GW band calculation,
      is similar to that of a small gap non-Kondo nontopological semiconductor.
      Additionally, the pressure-dependent electronic structure of YbB_{6} is
      investigated theoretically and found to transform into a p-d overlap semimetal
      with small Yb mixed valency. 

PMID- 27035313
TI  - Injection of Orbital Angular Momentum and Storage of Quantized Vortices in
      Polariton Superfluids.
AB  - We report the experimental investigation and theoretical modeling of a rotating
      polariton superfluid relying on an innovative method for the injection of angular
      momentum. This novel, multipump injection method uses four coherent lasers
      arranged in a square, resonantly creating four polariton populations propagating
      inwards. The control available over the direction of propagation of the
      superflows allows injecting a controllable nonquantized amount of optical angular
      momentum. When the density at the center is low enough to neglect polariton
      polariton interactions, optical singularities, associated with an interference
      pattern, are visible in the phase. In the superfluid regime resulting from the
      strong nonlinear polariton-polariton interaction, the interference pattern
      disappears and only vortices with the same sign are persisting in the system.
      Remarkably, the number of vortices inside the superfluid region can be controlled
      by controlling the angular momentum injected by the pumps. 

PMID- 27035314
TI  - Correlation-Driven Insulator-Metal Transition in Near-Ideal Vanadium Dioxide
      Films.
AB  - We use polarization- and temperature-dependent x-ray absorption spectroscopy, in
      combination with photoelectron microscopy, x-ray diffraction, and electronic
      transport measurements, to study the driving force behind the insulator-metal
      transition in VO_{2}. We show that both the collapse of the insulating gap and
      the concomitant change in crystal symmetry in homogeneously strained single
      crystalline VO_{2} films are preceded by the purely electronic softening of
      Coulomb correlations within V-V singlet dimers. This process starts 7 K (+/-0.3 
      K) below the transition temperature, as conventionally defined by electronic
      transport and x-ray diffraction measurements, and sets the energy scale for
      driving the near-room-temperature insulator-metal transition in this
      technologically promising material. 

PMID- 27035315
TI  - Variable-Range Hopping through Marginally Localized Phonons.
AB  - We investigate the effect of coupling Anderson localized particles in one
      dimension to a system of marginally localized phonons having a symmetry protected
      delocalized mode at zero frequency. This situation is naturally realized for
      electrons coupled to phonons in a disordered nanowire as well as for ultracold
      fermions coupled to phonons of a superfluid in a one-dimensional disordered trap.
      To determine if the coupled system can be many-body localized we analyze the
      phonon-mediated hopping transport for both the weak and strong coupling regimes.
      We show that the usual variable-range hopping mechanism involving a low-order
      phonon process is ineffective at low temperature due to discreteness of the bath
      at the required energy. Instead, the system thermalizes through a many-body
      process involving exchange of a diverging number n?-logT of phonons in the low
      temperature limit. This effect leads to a highly singular prefactor to Mott's
      well-known formula and strongly suppresses the variable range hopping rate.
      Finally, we comment on possible implications of this physics in higher
      dimensional electron-phonon coupled systems. 

PMID- 27035316
TI  - Noise Suppression Using Symmetric Exchange Gates in Spin Qubits.
AB  - We demonstrate a substantial improvement in the spin-exchange gate using
      symmetric control instead of conventional detuning in GaAs spin qubits, up to a
      factor of six increase in the quality factor of the gate. For symmetric
      operation, nanosecond voltage pulses are applied to the barrier that controls the
      interdot potential between quantum dots, modulating the exchange interaction
      while maintaining symmetry between the dots. Excellent agreement is found with a
      model that separately includes electrical and nuclear noise sources for both
      detuning and symmetric gating schemes. Unlike exchange control via detuning, the
      decoherence of symmetric exchange rotations is dominated by rotation-axis
      fluctuations due to nuclear field noise rather than direct exchange noise. 

PMID- 27035317
TI  - p-State Luminescence in CdSe Nanoplatelets: Role of Lateral Confinement and a
      Longitudinal Optical Phonon Bottleneck.
AB  - We evidence excited state emission from p states well below ground state
      saturation in CdSe nanoplatelets. Size-dependent exciton ground and excited state
      energies and population dynamics are determined by four independent methods: time
      resolved PL, time-integrated PL, rate equation modeling, and Hartree renormalized
      k.p calculations-all in very good agreement. The ground state-excited state
      energy spacing strongly increases with the lateral platelet quantization.
      Depending on its detuning to the LO phonon energy, the PL decay of CdSe platelets
      is governed by a size tunable LO phonon bottleneck, related to the low exciton
      phonon coupling, very large oscillator strength, and energy spacing of both
      states. This is, for instance, ideal to tune lasing properties. CdSe platelets
      are perfectly suited to control the exciton-phonon interaction by changing their
      lateral size while the optical transition energy is determined by their
      thickness. 

PMID- 27035318
TI  - Coulomb Interaction Effect in Weyl Fermions with Tilted Energy Dispersion in Two
      Dimensions.
AB  - Weyl fermions with tilted linear dispersions characterized by several different
      velocities appear in some systems including the quasi-two-dimensional organic
      semiconductor alpha-(BEDT-TTF)_{2}I_{3} and three-dimensional WTe_{2}. The
      Coulomb interaction between electrons modifies the velocities in an essential way
      in the low-energy limit, where the logarithmic corrections dominate. Taking into
      account the coupling to both the transverse and longitudinal electromagnetic
      fields, we derive the renormalization group equations for the velocities of the
      tilted Weyl fermions in two dimensions, and found that they increase as the
      energy decreases and eventually hit the speed of light c to result in the
      Cherenkov radiation. Especially, the system restores the isotropic Weyl cone even
      when the bare Weyl cone is strongly tilted and the velocity of electrons becomes
      negative in certain directions. 

PMID- 27035319
TI  - Two-Fluid Theory for Spin Superfluidity in Magnetic Insulators.
AB  - We investigate coupled spin and heat transport in easy-plane magnetic insulators.
      These materials display a continuous phase transition between normal and
      condensate states that is controlled by an external magnetic field. Using
      hydrodynamic equations supplemented by Gross-Pitaevski phenomenology and
      magnetoelectric circuit theory, we derive a two-fluid model to describe the
      dynamics of thermal and condensed magnons, and the appropriate boundary
      conditions in a hybrid normal-metal-magnetic-insulator-normal-metal
      heterostructure. We discuss how the emergent spin superfluidity can be
      experimentally probed via a spin Seebeck effect measurement. 

PMID- 27035320
TI  - Strain-Engineered Multiferroicity in Pnma NaMnF_{3} Fluoroperovskite.
AB  - In this study we show from first principles calculations the possibility to
      induce multiferroic and magnetoelectric functional properties in the Pnma
      NaMnF_{3} fluoroperovskite by means of epitaxial strain engineering.
      Surprisingly, we found a very strong nonlinear polarization-strain coupling that
      drives an atypical amplification of the ferroelectric polarization for either
      compression or expansion of the cell. This property is associated with a
      noncollinear antiferromagnetic ordering, which induces a weak ferromagnetism
      phase and makes the strained NaMnF_{3} fluoroperovskite multiferroic. The
      magnetoelectric response was calculated and it was found to be composed of linear
      and nonlinear components with amplitudes similar to the ones of Cr_{2}O_{3}.
      These findings show that it is possible to move the fluoride family toward
      functional applications with unique responses. 

PMID- 27035321
TI  - Tuning Photoluminescence Response by Electric Field in Electrically Soft
      Ferroelectrics.
AB  - We show that an electrically soft ferroelectric host can be used to tune the
      photoluminescence (PL) response of rare-earth emitter ions by external electric
      field. The proof of this concept is demonstrated by changing the PL response of
      the Eu^{3+} ion by electric field on a model system Eu-doped
      0.94(Na_{1/2}Bi_{1/2}TiO_{3})-0.06(BaTiO_{3}). We also show that new channels of
      radiative transitions, forbidden otherwise, open up due to positional disorder in
      the system, which can as well be tuned by electric field. 

PMID- 27035322
TI  - Wave-Number-Dependent Gilbert Damping in Metallic Ferromagnets.
AB  - A wave-number-dependent dissipative term to magnetization dynamics, mirroring the
      conservative term associated with exchange, has been proposed recently for
      ferromagnetic metals. We present measurements of wave-number-(k-)dependent
      Gilbert damping in three metallic ferromagnets, NiFe, Co, and CoFeB, using
      perpendicular spin wave resonance up to 26 GHz. In the thinnest films accessible,
      where classical eddy-current damping is negligible, size effects of Gilbert
      damping for the lowest and first excited modes support the existence of a k^{2}
      term. The new term is clearly separable from interfacial damping typically
      attributed to spin pumping. Higher-order modes in thicker films do not show
      evidence of enhanced damping, attributed to a complicating role of conductivity
      and inhomogeneous broadening. Our extracted magnitude of the k^{2} term,
      Deltaalpha_{kE}^{*}=Deltaalpha_{0}^{*}+A_{k}^{*}k^{2}, where A_{k}^{*}=0.08-0.1 
      nm^{2} in the three materials, is an order of magnitude lower than that
      identified in prior experiments on patterned elements. 

PMID- 27035323
TI  - Frustration and Self-Ordering of Topological Defects in Ferroelectrics.
AB  - A first-principles-based effective Hamiltonian technique is used to investigate
      the interplay between geometrical frustration and the ordering of topological
      defects in a ferroelectric nanocomposite consisting of a square array of
      BaTiO_{3} nanowires embedded in a Ba_{0.15}Sr_{0.85}TiO_{3} matrix. Different
      arrangements of the wires' chiralities geometrically frustrate the matrix, which
      in response exhibits point topological defects featuring self-assembled ordered
      structures spatially fluctuating down to the lowest temperatures. These
      fluctuations thereby endow the system with residual configurational entropy from
      which many properties characteristic of geometric frustration, such as the ground
      state degeneracy and the broadness of the dielectric response, are further found
      to originate. 

PMID- 27035324
TI  - Dynamic Stratification in Drying Films of Colloidal Mixtures.
AB  - In simulations and experiments, we study the drying of films containing mixtures
      of large and small colloidal particles in water. During drying, the mixture
      stratifies into a layer of the larger particles at the bottom with a layer of the
      smaller particles on top. We developed a model to show that a gradient in osmotic
      pressure, which develops dynamically during drying, is responsible for the
      segregation mechanism behind stratification. 

PMID- 27035325
TI  - Icariin regulates systemic iron metabolism by increasing hepatic hepcidin
      expression through Stat3 and Smad1/5/8 signaling.
AB  - Systemic iron homeostasis is strictly controlled under normal conditions to
      ensure a balance between the absorption, utilization, storage and recycling of
      iron. The hepcidin-ferroportin (FPN) axis is of critical importance in the
      maintenance of iron homeostasis. Hepcidin deficiency gives rise to enhanced
      dietary iron absorption, as well as to increased iron release from macrophages,
      and this in turn results in iron accumulation in the plasma and organs, and is
      associated with a range of tissue pathologies. Low hepcidin levels have been
      demonstrated in most forms of hereditary hemochromatosis (HH), as well as in beta
      thalassemia. Therapies that increase hepcidin concentrations may potentially play
      a role in the treatment of these iron overload-related diseases. To date, natural
      compounds have not been extensively investigated for this purpose, to the best of
      our knowledge. Thus, in the present study, we screened natural compounds that
      have the potential to regulate hepcidin expression. By performing hepcidin
      promoter-luciferase assay, RT-qPCR and animal experiments, we demonstrated that
      icariin and berberine were potent stimulators of hepcidin transcription.
      Mechanistic experiments indicated that icariin and berberine increased hepcidin
      expression by activating the signal transducer and activator of transcription 3
      (Stat3) and Smad1/5/8 signaling pathways. The induction of hepcidin was confirmed
      in mice following icariin administration, coupled with associated changes in
      serum and tissue iron concentrations. In support of these findings, the icariin
      analogues, epimedin A, B and C, also increased hepatic hepcidin expression.
      However, these changes were not observed in hepcidin-deficient [Hamp1-/- or Hamp1
      knockout (KO)] mice following icariin administration, thereby verifying hepatic
      hepcidin as the target of icariin. Although berberine exhibited a robust capacity
      to promote hepcidin expression in vitro, it failed to alter hepcidin expression
      in mice. Taken together, the findings of the present study suggest that icariin
      exhibits a robust capacity to increase hepatic hepcidin expression and to
      modulate systemic iron homeostasis. The present study therefore highlights the
      significance of using natural compounds to ameliorate iron disorders through the
      regulation of hepcidin expression.

PMID- 27035326
TI  - Stromal interaction molecule 1 plays an important role in gastric cancer
      progression.
AB  - Studies have shown that stromal interaction molecule 1 (STIM1) is expressed in a
      variety of cancers and is related to tumor growth. The present study aimed to
      investigate the expression and roles of STIM1 in gastric carcinoma.
      Immunohistochemistry and western blotting revealed that STIM1 was expressed at
      higher levels in gastric cancer tissues (82%) than these levels in normal gastric
      tissues (42%). In addition, STIM1 was also expressed in tumor vascular
      endothelial cells. The effects of STIM1 on proliferation, apoptosis, adhesion,
      invasion and migration of gastric cancer cells were detected by MTT assay, flow
      cytometry, cell adhesion assay and Transwell assay, respectively. The results
      shown that STIM1 knockdown did not alter proliferation or apoptosis, but promoted
      cell adhesion and inhibited migration and invasion in the gastric cancer cells.
      In addition, STIM1 knockdown did not alter the expression or phosphorylation of
      mitogen-activated protein kinase (MEK) or extracellular signal-regulated kinase
      (ERK), implying that STIM1 affected gastric cancer cell migration through a
      pathway independent of the MEK/ERK pathway. 

PMID- 27035327
TI  - shRNA-mediated RPS15A silencing inhibits U937 acute myeloid leukemia cell
      proliferation and enhances apoptosis.
AB  - Ribosomal protein S15a (RPS15A), which is a component of the 40S ribosomal
      subunit, is able to promote mRNA/ribosome interaction during the early stage of
      translation. Previous studies have demonstrated that RPS15A regulates cell growth
      and is involved in several types of human cancer. The aim of the present study
      was to investigate the role of RPS15A in acute myeloid leukemia (AML). Lentivirus
      delivered short hairpin RNA (shRNA) was used to silence RPS15A expression in the
      U937 AML cell line. Subsequently, the effects of RPS15A silencing on cell
      viability, cell cycle progression and apoptosis were investigated. The results
      indicated that RPS15A knockdown significantly inhibited cell growth. Furthermore,
      flow cytometric analysis demonstrated that the majority of U937 cells were
      arrested in G0/G1 phase and sub-G1 phase after RPS15A knockdown, as determined
      using propidium iodide staining. In addition, U937 cells underwent apoptosis in
      response to RPS15A silencing, as determined using Annexin V/7-aminoactinomycin D
      staining. In conclusion, the present study provides novel evidence indicating
      that RPS15A modulates AML cell growth in vitro, and may be considered a novel
      therapeutic target for the treatment of AML. 

PMID- 27035328
TI  - Cathelicidin-related antimicrobial peptide modulates the severity of acute
      pancreatitis in mice.
AB  - The present study aimed to investigate the immunomodulatory effects of mouse
      cathelicidin-related antimicrobial peptide (CRAMP) on experimental acute
      pancreatitis (AP). AP is a common clinical condition characterized by acute
      abdominal inflammation. Innate immune cells and mediators are intrinsically
      linked to the pathogenesis of AP. Cathelicidins are innate immunity-derived
      antimicrobial peptides that exert immunomodulatory effects on various host cells.
      However, how cathelicidins are involved and modulate the severity and
      inflammatory responses of AP remains unclear. In the present study, the mouse
      CRAMP gene-deficient cnlp-/- mice and their wild-type C57BL/6J littermates were
      induced with AP by multiple hourly injections of supramaximal doses of caerulein.
      Serum amylase levels, pancreatic myeloperoxidase activity and histological
      examination were performed in order to determine the disease severity and the
      levels of inflammatory cytokines. Disease severity and inflammatory markers were
      subsequently evaluated in the control mice, cnlp-/- C57BL/6J mice with AP, and
      wild-type C57BL/6J mice with AP. The results demonstrated that cnlp-/- mice
      exhibited a more severe phenotype and inflammatory response following AP
      induction compared with the wild-type mice, as evidenced by increased serum
      amylase levels, pancreatic myeloperoxidase release, and early inflammatory
      mediator tumor necrosis factor-alpha production. Histological examination
      confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition.
      These results indicate that CRAMP may be considered a novel modulatory mediator
      in mouse experimental AP. 

PMID- 27035329
TI  - Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin
      2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist
      Selectivity.
AB  - Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3
      receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and
      D3R were higher when determined in competition with the agonist radioligand
      [(3)H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist
      radioligand [(3)H]N-methylspiperone. Although 1 was confirmed as a D2R
      preferential agonist, its selectivity in binding and functional studies was lower
      than previously reported. All analogues were determined to be D2R/D3R agonists in
      both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for
      the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted
      analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved
      affinity at D2R over 1 with neither a loss of efficacy nor an increase in
      selectivity. Computational modeling provided a structural basis for the D2R
      selectivity of 1, illustrating how subtle differences in the highly homologous
      orthosteric binding site (OBS) differentially affect D2R/D3R affinity and
      functional efficacy. 

PMID- 27035330
TI  - Hypoxia is important in F-18 FDG accumulation in thecoma-fibroma tumors on F-18
      FDG PET/CT scans.
AB  - Several studies have noted benign thecoma-fibroma tumors with positive F-18
      fluorodeoxyglucose (FDG) accumulation mimicking malignant ovarian tumors
      following F-18 FDG positron emission tomography (PET). The present study analyzed
      four cases with false-positive F-18 FDG PET/computed tomography (CT) diagnoses of
      thecoma-fibroma tumors as malignant tumors due to F-18 FDG accumulation, compared
      with eight cases of FDG-positive ovarian cancers and two cases of FDG-negative
      fibromas. Hypoxia inducible factor (HIF)-1alpha expression was examined in the
      six thecoma-fibroma tumors using reverse transcription-polymerase chain reaction
      (RT-PCR). The four F-18 FDG-positive cases exhibited higher cellularity, maximum
      standard uptake and signal intensity on T2-weighted imaging, and gadolinium (Gd)
      enhancement using magnetic resonance imaging than the two FDG-negative fibroma
      cases. In the F-18 FDG-positive thecoma-fibroma group, Ki-67 expression was low
      and LAT1 expression was not identified, ruling out the diagnosis and potential
      for malignancy. However, considerable glucose transporter 1, HIF-1alpha, and
      vascular endothelial growth factor expression was observed. HIF-1alpha expression
      was elevated in all four false-positive cases by RT-PCR. From these results, it
      was hypothesized that hypoxia due to elevated cellularity may stimulate HIF
      1alpha expression and be associated with F-18 FDG accumulation in F-18-positive
      thecoma-fibroma tumors. 

PMID- 27035331
TI  - Lycopene protects human SH-SY5Y neuroblastoma cells against hydrogen peroxide
      induced death via inhibition of oxidative stress and mitochondria-associated
      apoptotic pathways.
AB  - Oxidative stress, which is characterized by excessive production of reactive
      oxygen species (ROS), is a common pathway that results in neuronal injury or
      death due to various types of pathological stress. Although lycopene has been
      identified as a potent antioxidant, its effect on hydrogen peroxide (H2O2)
      induced neuronal damage remains unclear. In the present study, pretreatment with
      lycopene was observed to protect SH-SY5Y neuroblastoma cells against H2O2-induced
      death via inhibition of apoptosis resulting from activation of caspase-3 and
      translocation of apoptosis inducing factor (AIF) to the nucleus. Furthermore, the
      over-produced ROS, as well as the reduced activities of anti-oxidative enzymes,
      superoxide dismutase and catalase, were demonstrated to be alleviated by
      lycopene. Additionally, lycopene counteracted H2O2-induced mitochondrial
      dysfunction, which was evidenced by suppression of mitochondrial permeability
      transition pore opening, attenuation of the decline of the mitochondrial membrane
      potential, and inhibition of the increase of Bax and decrease of Bcl-2 levels
      within the mitochondria. The release of cytochrome c and AIF from the
      mitochondria was also reduced. These results indicate that lycopene is a potent
      neuroprotectant against apoptosis, oxidative stress and mitochondrial
      dysfunction, and could be administered to prevent neuronal injury or death. 

PMID- 27035332
TI  - Genomic and immunologic factors associated with viral pathogenesis in a lethal
      EV71 infected neonatal mouse model.
AB  - Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) has emerged
      as a major health problem in China and worldwide. The present study aimed to
      understand the virological features of EV71 and host responses resulting from
      EV71 infection. Six different EV71 strains were isolated from HFMD patients with
      severe or mild clinical symptoms, and were analyzed for pathogenicity in vitro
      and in vivo. The results demonstrated that the six virus strains exhibited
      similar cytopathogenic effects on susceptible MA104 cells. However, marked
      differences in histological and immunopathological changes were observed when
      mice were inoculated with the different virus strains. Thus, the viruses studied
      were divided into two groups, highly or weakly pathogenic. Two representative
      virus strains, JN200804 and JN200803 (highly and weakly pathogenic, respectively)
      were studied further to investigate pathogenicity-associated factors, including
      genetic mutations and immunopathogenesis. The present study has demonstrated that
      highly pathogenic strains have stable genome and amino acid sequences. Notably,
      the present study demonstrated that a highly pathogenic strain induced a
      significant increase of the bulk CD4 T cell levels at 3 days post-inoculation. In
      conclusion, the current study demonstrates that genomic and immunologic factors
      may be responsible for the multiple tissue damage caused by highly pathogenic
      EV71 infection. 

PMID- 27035333
TI  - miR-30a-5p in the tumorigenesis of renal cell carcinoma: A tumor suppressive
      microRNA.
AB  - Renal cell carcinoma (RCC) is the most common type of malignant tumor of the
      adult kidney and has a poor prognosis. MicroRNAs (miRs) are important in a wide
      range of biological and pathological processes, including cell differentiation,
      migration, growth, proliferation, apoptosis and metabolism. The present study
      aimed to determine the role exerted by miR-30a-5p in the tumorigenesis of RCC.
      The expression levels of miR-30a-5p in RCC tissues and RCC-derived cells were
      demonstrated to be significantly downregulated by real-time quantitative
      polymerase chain reaction (RT-qPCR). Wound scratch assay, cell proliferation
      assay and flow cytometric analysis revealed that the abilities of migration and
      proliferation of the RCC-derived cells were suppressed, whereas cell apoptosis
      was promoted, when miR-30a-5p was overexpressed in these cells. N
      acetylgalactosaminyltransferase 7 (GALNT7) was predicted to be one target gene of
      miR-30a-5p by bioinformatics analysis. Luciferase reporter assay, RT-qPCR and
      western blotting were performed to confirm that GALNT7 is the direct conserved
      target of miR-30a-5p. These results suggested that miR-30a-5p has a tumor
      suppressive role in the tumorigenesis of RCC. 

PMID- 27035334
TI  - Antiadipogenic effects of subthermal electric stimulation at 448 kHz on
      differentiating human mesenchymal stem cells.
AB  - The 448 kHz capacitive-resistive electric transfer (CRET) is an electrothermal
      therapy currently applied in anticellulite and antiobesity treatments. The aim of
      the present study was to determine whether exposure to the CRET electric signal
      at subthermal doses affected early adipogenic processes in adipose-derived stem
      cells (ADSC) from human donors. ADSC were incubated for 2 or 9 days in the
      presence of adipogenic medium, and exposed or sham-exposed to 5 min pulses of 448
      kHz electric signal at 50 uA/mm2 during the last 48 h of the incubation.
      Colorimetric, immunofluorescence, western blotting and reverse transcription
      quantitative polymerase chain reaction assays were performed to assess adipogenic
      differentiation of the ADSC. Electric stimulation significantly decreased
      cytoplasmic lipid content, after both 2 and 9 days of differentiation. The
      antiadipogenic response in the 9 day samples was accompanied by activation of
      mitogen-activated protein kinase kinase 1/2, decreased expression and partial
      inactivation of peroxisome proliferator-activated receptor (PPAR) gamma, which
      was translocated from the nucleus to the cytoplasm, together with a significant
      decrease in the expression levels of the PPARG1 gene, perilipin, angiopoietin
      like protein 4 and fatty acid synthase. These results demonstrated that
      subthermal stimulation with CRET interferes with the early adipogenic
      differentiation in ADSC, indicating that the electric stimulus itself can
      modulate processes controlling the synthesis and mobilization of fat, even in the
      absence of the concomitant thermal and mechanical components of the
      thermoelectric therapy CRET. 

PMID- 27035335
TI  - Microarray expression profile analysis of aberrant long non-coding RNAs in
      esophageal squamous cell carcinoma.
AB  - Increasing evidence indicates that long non-coding RNA (lncRNA) plays an
      important role in tumorigenesis. However, the function and regulatory mechanism
      of lncRNAs are still unclear in esophageal squamous cell carcinoma (ESCC). To
      address this challenge, we screened lncRNAs expression profiles in 3 pairs of
      ESCC and matched non-cancerous tissues by microarray assay and identified the
      relationship between lncRNAs expression in ESCC tissue and clinicopathological
      characteristics and prognosis of patients with ESCC. We found 182 lncRNAs that
      were significantly differently expressed in ESCC tissues versus the matched non
      cancerous tissues. Gene ontology and pathway analysis results suggested that the
      primary biological processes of these genes were involved in extracellular
      matrix, immune responses, cell differentiation and cell proliferation. Through
      cis and trans analyzing, we found 4 lncRNAs (ENST00000480669, NONHSAT104436,
      NONHSAT126998 and NONHSAT112918) may play important roles in tumorigenesis of
      ESCC. The four lncRNAs were checked in 73 patients with ESCC. The results showed
      that they mainly related to tumor metastasis. Kaplan-Meier survival analysis
      showed that high expression of NONHSAT104436, NONHSAT126998 and low expression of
      ENST00000480669 were related to poor 3-year overall survival (P=0.003, 0.032 and
      0.040, respectively). Multivariate analysis showed that NONHSAT104436 was an
      independent prognostic factor (P=0.017). Thus we concluded that, lncRNAs showed
      differently expression patterns in ESCC versus matched non-cancerous tissues, and
      aberrantly expressed lncRNA may play important roles in ESCC development and
      progression. Interestingly, the overexpression of NONHSAT104436 was tightly
      correlated with distant metastasis and, poor survival rate, which might indicate
      that NONHSAT104436 might play a very important part in ESCC tumor progression. 

PMID- 27035336
TI  - Coupling Gd-DTPA with a bispecific, recombinant protein anti-EGFR-iRGD complex
      improves tumor targeting in MRI.
AB  - Recombinant anti-epidermal growth factor receptor-internalizing arginine-glycine
      aspartic acid (anti-EGFR single-domain antibody fused with iRGD peptide) protein
      efficiently targets the EGFR extracellular domain and integrin alphavbeta/beta5,
      and shows a high penetration into cells. Thus, this protein may improve
      penetration of conjugated drugs into the deep zone of gastric cancer
      multicellular 3D spheroids. In the present study, a novel tumor-targeting
      contrast agent for magnetic resonance imaging (MRI) was developed, by coupling
      gadolinium-diethylene triamine pentaacetate (Gd-DTPA) with the bispecific
      recombinant anti-EGFR-iRGD protein. The anti-EGFR-iRGD protein was extracted from
      Escherichia coli and Gd was loaded onto the recombinant protein by chelation
      using DTPA anhydride. Single-targeting agent anti-EGFR-DTPA-Gd, which served as
      the control, was also prepared. The results of the present study showed that anti
      EGFR-iRGD-DTPA-Gd exhibited no significant cyto-toxicity to human gastric
      carcinoma cells (BGC-823) under the experimental conditions used. Compared with a
      conventional contrast agent (Magnevist), anti-EGFR-iRGD-DTPA-Gd showed higher T1
      relaxivity (10.157/mM/sec at 3T) and better tumor-targeting ability. In addition,
      the signal intensity and the area under curve for the enhanced signal time in
      tumor, in vivo, were stronger than Gd-DTPA alone or the anti-EGFR-Gd control.
      Thus, Gd-labelled anti-EGFR-iRGD has potential as a tumor-targeting contrast
      agent for improved MRI. 

PMID- 27035337
TI  - Co-inhibition of miRNA-21 and miRNA-221 induces apoptosis by enhancing the p53
      mediated expression of pro-apoptotic miRNAs in laryngeal squamous cell carcinoma.
AB  - Dysregulation of a numerous microRNAs (miRNAs) has been implicated in laryngeal
      squamous cell carcinoma (LSCC). Among those miRNAs, miR-21 and miR-221 are co
      overexpressed and commonly target the phosphatase and tensin homolog protein
      (PTEN) that is located in the PTEN-Akt signaling pathway. The present study
      investigated whether co-inhibition of miR-21 and miR-221 induced synergistic
      apoptosis of human LSCC cells. Methyl thiazolyl tetrazolium (MTT) and terminal
      deoxynucleotidyl-transferase-mediated deoxynucleotide triphosphate nick end
      labeling (TUNEL) assays were used to observe the potential effect of miR-21 and
      miR-221 on cell viability and apoptosis in cells co-transfected with anti-miRNA
      oligonucleotide (AMO)-21 and AMO-221. The protein expression levels of PTEN, Akt
      and p53 were determined by western blotting. The cellular abundance of 6 pro
      apoptotic miRNAs transcribed by p53 mediation, consisting of miR-15a, miR-16-1,
      miR-26a, miR-34a, miR-143 and miR-203, was measured with using reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR). MTT results
      indicate that in vitro co-transfection of AMO-21 and AMO-221 leads to a decline
      in cell viability, compared with the transfection of AMO alone. This result was
      verified by the detection of apoptosis using TUNEL assays. Co-transfection of AMO
      21 and AMO-221 resulted in a marked reduction in Akt phosphorylation and enhanced
      expression of PTEN and p53 were observed; consequently, leading to an
      amplification of the transcription of 6 pro-apoptotic miRNAs. The present
      findings confirmed that co-inhibition of miR-21 and miR-221 synergistically
      triggers cell apoptosis in vitro. The altered PTEN-Akt signaling and p53-mediated
      amplification of the transcription of pro-apoptotic miRNAs may be involved in the
      observed synergistic effect. The present study provides novel insights into the
      mechanism underlying apoptosis-associated miRNA-miRNA mutual regulation in LSCC. 

PMID- 27035338
TI  - Knockdown of Nogo gene by short hairpin RNA interference promotes functional
      recovery of spinal cord injury in a rat model.
AB  - The specific myelin component Nogo protein is one of the major inhibitory
      molecules of spinal cord axonal outgrowth following spinal cord injury. The
      present study aimed to investigate the effects of silencing Nogo protein with
      shRNA interference on the promotion of functional recovery in a rat model with
      spinal cord hemisection. Nogo-A short hairpin RNAs (Nogo shRNAs) were constructed
      and transfected into rats with spinal cord hemisection by adenovirus-mediated
      transfection. Reverse transcription-polymerase chain reaction and western
      blotting were performed to analyze the expression of Nogo-A and Growth Associated
      Protein 43 (GAP-43). In addition, Basso Beattie Bresnahan (BBB) scores were used
      to assess the functional recovery of rats following spinal cord injury. The
      results demonstrated that expression of the Nogo-A gene was observed to be
      downregulated following transfection and GAP-43 expression was observed to
      increase. The BBB scores were increased following treatment with Nogo shRNAs,
      indicating functional recovery of the injured nerves. Thus, Nogo-A shRNA
      interference can knockdown Nogo gene expression and upregulate GAP-43 to promote
      the functional recovery of spinal cord injury in rats. This finding may advance
      progress toward assisting the regeneration of injured neurons through the use of
      Nogo-A shRNA. 

PMID- 27035339
TI  - Differential Responses of Pattern Recognition Receptors to Outer Membrane
      Vesicles of Three Periodontal Pathogens.
AB  - Highly purified outer membrane vesicles (OMVs) of the periodontal pathogens,
      Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia were
      produced using tangential flow ultrafiltration, ultracentrifugation and Optiprep
      density gradient separation. Cryo-TEM and light scattering showed OMVs to be
      single lipid-bilayers with modal diameters of 75 to 158 nm. Enumeration of OMVs
      by nanoparticle flow-cytometry at the same stage of late exponential culture
      indicated that P. gingivalis was the most prolific OMV producer. P. gingivalis
      OMVs induced strong TLR2 and TLR4-specific responses and moderate responses in
      TLR7, TLR8, TLR9, NOD1 and NOD2 expressing-HEK-Blue cells. Responses to T.
      forsythia OMVs were less than those of P. gingivalis and T. denticola OMVs
      induced only weak responses. Compositional analyses of OMVs from the three
      pathogens demonstrated differences in protein, fatty acids, lipopolysaccharide,
      peptidoglycan fragments and nucleic acids. Periodontal pathogen OMVs induced
      differential pattern recognition receptor responses that have implications for
      their role in chronic periodontitis. 

PMID- 27035340
TI  - The qEEG Signature of Selective NMDA NR2B Negative Allosteric Modulators; A
      Potential Translational Biomarker for Drug Development.
AB  - The antidepressant activity of the N-methyl-D-aspartate (NMDA) receptor channel
      blocker, ketamine, has led to the investigation of negative allosteric modulators
      (NAMs) selective for the NR2B receptor subtype. The clinical development of NR2B
      NAMs would benefit from a translational pharmacodynamic biomarker that
      demonstrates brain penetration and functional inhibition of NR2B receptors in
      preclinical species and humans. Quantitative electroencephalography (qEEG) is a
      translational measure that can be used to demonstrate pharmacodynamic effects
      across species. NMDA receptor channel blockers, such as ketamine and
      phencyclidine, increase the EEG gamma power band, which has been used as a
      pharmacodynamic biomarker in the development of NMDA receptor antagonists.
      However, detailed qEEG studies with ketamine or NR2B NAMs are lacking in nonhuman
      primates. The aim of the present study was to determine the effects on the qEEG
      power spectra of the NR2B NAMs traxoprodil (CP-101,606) and BMT-108908 in
      nonhuman primates, and to compare them to the NMDA receptor channel blockers,
      ketamine and lanicemine. Cynomolgus monkeys were surgically implanted with EEG
      radio-telemetry transmitters, and qEEG was measured after vehicle or drug
      administration. The relative power for a number of frequency bands was
      determined. Ketamine and lanicemine increased relative gamma power, whereas the
      NR2B NAMs traxoprodil and BMT-108908 had no effect. Robust decreases in beta
      power were elicited by ketamine, traxoprodil and BMT-108908; and these agents
      also produced decreases in alpha power and increases in delta power at the doses
      tested. These results suggest that measurement of power spectra in the beta and
      delta bands may represent a translational pharmacodynamic biomarker to
      demonstrate functional effects of NR2B NAMs. The results of these studies may
      help guide the selection of qEEG measures that can be incorporated into early
      clinical evaluation of NR2B NAMs in healthy humans. 

PMID- 27035341
TI  - Adipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat
      Accumulation.
AB  - While the role of both elevated levels of circulating bacterial cell wall
      components and adipose tissue in hepatic fat accumulation has been recognized, it
      has not been considered that the bacterial components-recognizing adipose tissue
      receptors contribute to the hepatic fat content. In this study we found that the
      expression of adipose tissue bacterial flagellin (FLG)-recognizing Toll-like
      receptor (TLR) 5 associated with liver fat content (r = 0.699, p = 0.003) and
      insulin sensitivity (r = -0.529, p = 0.016) in humans (n = 23). No such
      associations were found for lipopolysaccharides (LPS)-recognizing TLR4. To study
      the underlying molecular mechanisms of these associations, human HepG2 hepatoma
      cells were exposed in vitro to the conditioned culture media derived from FLG or
      LPS-challenged human adipocytes. The adipocyte-mediated effects were also
      compared to the effects of direct HepG2 exposure to FLG and LPS. We found that
      the media derived from FLG-treated adipocytes stimulated fat accumulation in
      HepG2 cells, whereas either media derived from LPS-treated adipocytes or direct
      FLG or LPS exposure did not. This is likely due to that FLG-treatment of
      adipocytes increased lipolysis and secretion of glycerol, which is known to serve
      a substrate for triglyceride synthesis in hepatocytes. Similarly, only FLG-media
      significantly decreased insulin signaling-related Akt phosphorylation, IRS1
      expression and mitochondrial respiratory chain ATP5A. In conclusion, our results
      suggest that the FLG-induced TLR5 activation in adipocytes increases glycerol
      secretion from adipocytes and decreases insulin signaling and mitochondrial
      functions, and increases fat accumulation in hepatocytes. These mechanisms could,
      at least partly, explain the adipose tissue TLR5 expression associated with liver
      fat content in humans. 

PMID- 27035342
TI  - On the Use of a Test to Exhaustion Specific to Tennis (TEST) with Ball Hitting by
      Elite Players.
AB  - PURPOSE: We aimed to a) introduce a new Test to Exhaustion Specific to Tennis
      (TEST) and compare performance (test duration) and physiological responses to
      those obtained during the 20-m multistage shuttle test (MSST), and b) determine
      to which extent those variables correlate with performance level (tennis
      competitive ranking) for both test procedures. METHODS: Twenty-seven junior
      players (8 males, 19 females) members of the national teams of the French Tennis
      Federation completed MSST and TEST, including elements of the game (ball hitting,
      intermittent activity, lateral displacement), in a randomized order.
      Cardiorespiratory responses were compared at submaximal (respiratory compensation
      point) and maximal loads between the two tests. RESULTS: At the respiratory
      compensation point oxygen uptake (50.1 +/- 4.7 vs. 47.5 +/- 4.3 mL.min(-1).kg(
      1), p = 0.02), but not minute ventilation and heart rate, was higher for TEST
      compared to MSST. However, load increment and physiological responses at
      exhaustion did not differ between the two tests. Players' ranking correlated
      negatively with oxygen uptake measured at submaximal and maximal loads for both
      TEST (r = -0.41; p = 0.01 and -0.55; p = 0.004) and MSST (r = -0.38; P = 0.05 and
      -0.51; p = 0.1). CONCLUSION: Using TEST provides a tennis-specific assessment of
      aerobic fitness and may be used to prescribe aerobic exercise in a context more
      appropriate to the game than MSST. Results also indicate that VO2 values both at
      submaximal and maximal load reached during TEST and MSST are moderate predictors
      of players competitive ranking.

PMID- 27035344
TI  - Correction: Strong Selection at MHC in Mexicans since Admixture.

PMID- 27035343
TI  - Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of
      Early and Late Pathological Events through Proteomic Analysis.
AB  - The time-course of the pathological effects induced by the venom of the snake
      Bothrops asper in muscle tissue was investigated by a combination of histology,
      proteomic analysis of exudates collected in the vicinity of damaged muscle, and
      immunodetection of extracellular matrix proteins in exudates. Proteomic assay of
      exudates has become an excellent new methodological tool to detect key biomarkers
      of tissue alterations for a more integrative perspective of snake venom-induced
      pathology. The time-course analysis of the intracellular proteins showed an early
      presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal
      proteins increased later on. This underscores the rapid cytotoxic effect of
      venom, especially in muscle fibers, due to the action of myotoxic phospholipases
      A2, followed by the action of proteinases in the cytoskeleton of damaged muscle
      fibers. Similarly, the early presence of basement membrane (BM) and other
      extracellular matrix (ECM) proteins in exudates reflects the rapid microvascular
      damage and hemorrhage induced by snake venom metalloproteinases. The presence of
      fragments of type IV collagen and perlecan one hour after envenoming suggests
      that hydrolysis of these mechanically/structurally-relevant BM components plays a
      key role in the genesis of hemorrhage. On the other hand, the increment of some
      ECM proteins in the exudate at later time intervals is likely a consequence of
      the action of endogenous matrix metalloproteinases (MMPs) or of de novo synthesis
      of ECM proteins during tissue remodeling as part of the inflammatory reaction.
      Our results offer relevant insights for a more integrative and systematic
      understanding of the time-course dynamics of muscle tissue damage induced by B.
      asper venom and possibly other viperid venoms. 

PMID- 27035345
TI  - Effects of Topically Applied Vitamin D during Corneal Wound Healing.
AB  - Vitamin D is an important regulator of immune function and largely acts to dampen
      chronic inflammatory events in a variety of tissues. There is also accumulating
      evidence that vitamin D acts to enhance initial inflammation, beneficial during
      both infection and wound healing, and then promotes resolution and prevention of
      chronic, damaging inflammation. The current study examines the effect of topical
      vitamin D in a mouse of model of corneal epithelial wound healing, where acute
      inflammation is necessary for efficient wound closure. At 12 and 18 hours post
      wounding, vitamin D treatment significantly delayed wound closure by ~17% and
      increased infiltration of neutrophils into the central cornea. Basal epithelial
      cell division, corneal nerve density, and levels of VEGF, TGFbeta, IL-1beta, and
      TNFalpha were unchanged. However, vitamin D increased the production of the anti
      microbial peptide CRAMP 12 hours after wounding. These data suggest a possible
      role for vitamin D in modulating corneal wound healing and have important
      implications for therapeutic use of vitamin D at the ocular surface. 

PMID- 27035346
TI  - Neurological Impact of World War I on the Artistic Avant-Garde: The Examples of
      Andre Breton, Guillaume Apollinaire and Blaise Cendrars.
AB  - World War I erupted at a time when artistic avant-gardes were particularly
      thriving across Europe. Young poets, writers, painters and sculptors were called
      to arms or voluntary enrolled to fight, and several of them died during the
      conflict. Among others, it dramatically changed their creative output, either
      through specific wounds or through personal encounters and experiences. These
      individual events then significantly modified the course of the literary and
      artistic avant-garde movements. Three particularly illustrative examples of avant
      garde French poets are presented here: Andre Breton (1896-1966), Guillaume
      Apollinaire (1880-1918) and Blaise Cendrars (1887-1961). The deep source of the
      surrealist movement can indeed be found in Andre Breton's involvement as an
      auxiliary physician with critical interest in neuropsychiatry, which caused him
      to discover automatic writing. Guillaume Apollinaire's right temporal subdural
      hematoma strongly modified his emotional state and subsequent artistic
      activities. Alternatively, after losing his right, writing hand, Blaise Cendrars
      not only substituted it with a phantom but also rapidly switched from poetry to
      novels after he learnt to write with his left hand. 

PMID- 27035347
TI  - Molecular Evolution and Characterization of Hemagglutinin (H) in Peste des Petits
      Ruminants Virus.
AB  - Peste des Petits Ruminants (PPR) is an acute, highly contagious, and febrile
      viral disease that affects both domestic and wild small ruminants. The disease
      has become a major obstacle to the development of sustainable Agriculture.
      Hemagglutinin (H), the envelope glycoprotein of Peste des Petits Ruminants Virus
      (PPRV), plays a crucial role in regulating viral adsorption and entry, thus
      determining pathogenicity, and release of newly produced viral particles. In
      order to accurately understand the epidemic of the disease and the interactions
      between the virus and host, we launch the work. Here, we examined H gene from all
      four lineages of the PPRV to investigate evolutionary and epidemiologic dynamics
      of PPRV by the Bayesian method. In addition, we predicted positive selection
      sites due to selective pressures. Finally, we studied the interaction between H
      protein and SLAM receptor based on homology model of the complex. Phylogenetic
      analysis suggested that H gene can also be used to investigate evolutionary and
      epidemiologic dynamics of PPRV. Positive selection analysis identified four
      positive selection sites in H gene, in which only one common site (aa246) was
      detected by two methods, suggesting strong operation structural and/or functional
      constraint of changes on the H protein. This target site may be of interest for
      future mutagenesis studies. The results of homology modeling showed PPRVHv-shSLAM
      binding interface and MVH-maSLAM binding interface were consistent, wherein the
      groove in the B4 blade and B5 of the head domain of PPRVHv bound to the AGFCC'
      beta-sheets of the membrane-distal ectodomain of shSLAM. The binding regions
      could provide insight on the nature of the protein for epitope vaccine design,
      novel drug discovery, and rational drug design against PPRV. 

PMID- 27035348
TI  - Long-Term (7 Years) Follow-Up of Roux-en-Y Gastric Bypass on Obese Adolescent
      Patients (<18 Years).
AB  - BACKGROUND: Few data are available about obesity surgery in adolescent patients.
      OBJECTIVE: To assess long-term outcomes after laparoscopic Roux-en-Y gastric
      bypass (LRYGB) in patients <18 years. SETTING: University Hospital, Europe.
      METHODS: A retrospective study of prospectively collected data of patients <18
      years (childhood group; ChG) (n = 28) treated by LRYGB of which 19 were available
      for follow-up between 2.4 and 10.2 years (mean 7.2 years). This group of patients
      was matched with an adult control group (AdG) of randomly chosen patients with
      similar characteristics who underwent LRYGB during the same period. The extensive
      survey included a telephonic questionnaire. RESULTS: 19 (12 females) of the 28
      patients (67.9%) were available for follow-up. Preoperatively, 3 had type 2
      diabetes mellitus (T2DM), 1 arterial hypertension, 5 dyslipidemia and 1 sleep
      apnea. In the ChG, average BMI after 7 years dropped from 38.9 kg/m2
      preoperatively to 27.5 kg/m2. In the AdG, average BMI decreased from 39.4 to 27.1
      kg/m2 in the same time period (nonsignificant between groups). One patient in the
      ChG needed a reoperation (internal hernia) versus 3 patients in the AdG (1 leak,
      2 obstructions). All patients resolved their initial comorbidities. Two of 12
      female patients in the ChG became pregnant 6 and 8 years after surgery,
      respectively, despite seemingly adequate oral contraception. Compliance with
      postoperative guidelines was good in 16/19 patients in ChG and in 14/18 patients
      in the AdG. Overall degree of satisfaction was high: 8.2/10 (SD 1.2, range 6-10)
      in the ChG and 8.9/10 (SD 1.7, range 5-10) in the AdG. CONCLUSION: LRYGB seems to
      be safe, provide good weight loss, and cure comorbidities in an adolescent
      population. Satisfaction degree is high. Inadvertent pregnancy despite
      conventional contraception is a possible issue.

PMID- 27035349
TI  - A Well-Defined Readily Releasable Pool with Fixed Capacity for Storing Vesicles
      at Calyx of Held.
AB  - The readily releasable pool (RRP) of vesicles is a core concept in studies of
      presynaptic function. However, operating principles lack consensus definition and
      the utility for quantitative analysis has been questioned. Here we confirm that
      RRPs at calyces of Held from 14 to 21 day old mice have a fixed capacity for
      storing vesicles that is not modulated by Ca2+. Discrepancies with previous
      studies are explained by a dynamic flow-through pool, established during heavy
      use, containing vesicles that are released with low probability despite being
      immediately releasable. Quantitative analysis ruled out a posteriori explanations
      for the vesicles with low release probability, such as Ca2+-channel inactivation,
      and established unexpected boundary conditions for remaining alternatives.
      Vesicles in the flow-through pool could be incompletely primed, in which case the
      full sequence of priming steps downstream of recruitment to the RRP would have an
      average unitary rate of at least 9/s during heavy use. Alternatively, vesicles
      with low and high release probability could be recruited to distinct types of
      release sites; in this case the timing of recruitment would be similar at the two
      types, and the downstream transition from recruited to fully primed would be much
      faster. In either case, further analysis showed that activity accelerates the
      upstream step where vesicles are initially recruited to the RRP. Overall, our
      results show that the RRP can be well defined in the mathematical sense, and
      support the concept that the defining mechanism is a stable group of autonomous
      release sites. 

PMID- 27035350
TI  - Distribution of Telomeric Sequences (TTAGGG)n in Rearranged Chromosomes of
      Phyllotine Rodents (Cricetidae, Sigmodontinae).
AB  - Phyllotines are sigmodontine rodents endemic to South America with broad genetic
      variability, Robertsonian polymorphisms being the most frequent. Moreover, this
      taxon includes a species with multiple sex chromosomes, which is infrequent in
      mammals. However, molecular cytogenetic techniques have never been applied to
      phyllotines to elucidate their karyotypic evolution. We studied the chromosomes
      of 4 phyllotine species using FISH with a pantelomeric probe (TTAGGG)n. Graomys
      griseoflavus, Eligmodontia puerulus, and E. morgani are polymorphic for
      Robertsonian translocations, whereas Salinomys delicatus possesses XX/ XY1Y2 sex
      chromosomes. Telomeric signals were detected at both ends of all chromosomes of
      the studied species. In S. delicatus interstitial telomeric sequences (ITS) were
      observed in the 3 major chromosome pairs, which are equidistant from one of the
      telomeres in these chromosomes. These results suggest that ITS are important in
      the reshuffling of the highly derived karyotype of S. delicatus. Considering the
      phylogeny of phyllotines, the Robertsonian rearrangements of G. griseoflavus, E.
      puerulus, and E. morgani possibly represent chromosome fusions which have
      occurred independently. The pericentromeric regions of the biarmed chromosomes of
      these species do not contain telomeric sequences characteristic for strict
      fusions of recent origin, suggesting a common pattern of telomeric repeat loss
      during chromosomal evolution of these rodents. 

PMID- 27035351
TI  - Use of the Ella Danis stent in esophageal bleeding due to severe reflux
      esophagitis.

PMID- 27035352
TI  - Total occlusion of the esophagus following placement of an over-the-scope clip:
      an unusual complication, and how to solve it.

PMID- 27035353
TI  - Percutaneous transhepatic cholangioscopy-assisted repositioning of misplaced
      endoscopic ultrasound-guided pancreatic duct stent.

PMID- 27035354
TI  - Endoscopic removal of a 35-mm fish bone totally embedded in the gastric wall.

PMID- 27035355
TI  - Double papilla of Vater: a rare anatomic variant.

PMID- 27035356
TI  - MG132 Induces Expression of Monocyte Chemotactic Protein-Induced Protein 1 in
      Vascular Smooth Muscle Cells.
AB  - Monocyte chemoattractant protein-1 (MCP-1) has been reported to induce the
      expression of monocyte chemotactic protein-induced protein 1 (MCPIP1), which
      undergoes ubiquitination degradation. Therefore, we predict that in vascular
      smooth muscle (VSMCs), MCPIP1 may be induced by MCP-1 and undergo degradation,
      which can be inhibited by the proteasome inhibitor, MG132. Our results showed
      that treatment of human VSMCs with MCP-1 did not increase the expression of
      MCPIP1. Treatment with MG132, however, elevated MCPIP1 protein levels through
      stimulation of the gene transcription, but not through increasing protein
      stability. MCPIP1 expression induced by MG132 was inhibited by alpha-amanitin
      inhibition of gene transcription or cycloheximide inhibition of protein
      synthesis. Our further studies showed that MCPIP1 expression induced by MG132 was
      inhibited by the inhibitors of AKT and p38 kinase, suggesting a role of the AKT
      p38 pathway in MG132 effects. We also found that treatment with MG132 induces
      apoptosis, but overexpression of MCPIP1 inhibited bromodeoxyuridine (BrdU)
      incorporation of human VSMCs without induction of significant apoptosis. In
      summary, MCPIP1 expression is induced by MG132 likely through activation of the
      AKT-p38 pathway. MCPIP1 inhibits SMC proliferation without induction of
      apoptosis. J. Cell. Physiol. 232: 122-128, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27035357
TI  - Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of
      Microbiome-Behavior Relationships.
AB  - OBJECTIVES: The microbiota-gut-brain axis is increasingly implicated in obesity,
      anxiety, stress, and other health-related processes. Researchers have proposed
      that gut microbiota may influence dietary habits, and pathways through the
      microbiota-gut-brain axis make such a relationship feasible; however, few data
      bear on the hypothesis. As a first step in the development of a model system, the
      gut microbiome was examined in rat lines selectively outbred on a taste phenotype
      with biobehavioral profiles that have diverged with respect to energy regulation,
      anxiety, and stress. METHODS: Occidental low and high-saccharin-consuming rats
      were assessed for body mass and chow, water, and saccharin intake; littermate
      controls had shared cages with rats in the experimental group but were not
      assessed. Cecum and colon microbial communities were profiled using Illumina 16S
      rRNA sequencing and multivariate analysis of microbial diversity and composition.
      RESULTS: The saccharin phenotype was confirmed (low-saccharin-consuming rats,
      0.7Delta% [0.9Delta%]; high-saccharin-consuming rats, 28.1Delta% [3.6Delta%]).
      Regardless of saccharin exposure, gut microbiota differed between lines in terms
      of overall community similarity and taxa at lower phylogenetic levels.
      Specifically, 16 genera in three phyla distinguished the lines at a 10% false
      discovery rate. DISCUSSION: The study demonstrates for the first time that rodent
      lines created through selective pressure on taste and differing on functionally
      related correlates host different microbial communities. Whether the microbiota
      are causally related to the taste phenotype or its correlates remains to be
      determined. These findings encourage further inquiry on the relationship of the
      microbiome to taste, dietary habits, emotion, and health.

PMID- 27035358
TI  - Nurses' Perceptions of Diagnosis and Prognosis-Related Communication: An
      Integrative Review.
AB  - BACKGROUND: Disclosure of diagnostic and prognostic information has become the
      standard in the United States and increasingly around the world. Disclosure is
      generally identified as the responsibility of the physician. However, nurses are
      active participants in the process both intentionally and inadvertently. If not
      included in initial discussions regarding diagnosis and prognosis, the nurse may
      find it challenging to openly support the patient and family. OBJECTIVE: The aim
      of this study is to synthesize published literature regarding nurses' perceptions
      and experiences with diagnosis and prognosis-related communication. METHODS: The
      Whittemore and Knafl method guided the integrative review process. Electronic
      databases including Cumulative Index to Nursing and Allied Health Literature,
      Health Sciences in ProQuest, PubMed, and Web of Science were used to review the
      literature from 2000 to 2015. Constant comparison methods were used to analyze
      the data and develop themes. RESULTS: Thirty articles met all of the inclusion
      criteria and were included in this review. Several themes emerged from the data,
      including the nurse's role in the process of diagnosis and prognosis-related
      communication, barriers and difficulties related to communication, and positive
      and negative outcomes. CONCLUSIONS: Nurses play an integral role in the process
      of diagnostic and prognostic disclosure. Further exploration of both physician
      and patient perceptions of the nurse's role are needed. Interprofessional
      training regarding diagnosis and prognosis-related communication is essential to
      promote collaboration and better empower nurses in this process. IMPLICATIONS FOR
      PRACTICE: Nurses should aim to purposefully partner with physician colleagues to
      plan and participate in diagnostic and prognostic discussions. Nurses should
      identify opportunities to improve their knowledge, understanding, and comfort
      with challenging conversations.

PMID- 27035359
TI  - Astrocytes: inexplicable cells in neurodegeneration.
AB  - Astrocytes are the most explored non-neuronal cells in the brain under
      neurophysiological and neurodegenerative conditions. Extensive research has been
      done to understand their specific role during neuropathological conditions but
      still the existing findings could not conclude their mechanism of action and
      their specific role in neurodegenerative conditions. This review discusses their
      physiological and pathological roles, their activation, morphological alterations
      and their probable use in search of new therapeutic targets for the treatment of
      neurodegenerative diseases.

PMID- 27035360
TI  - Composition dependent reactivity of titanium oxide clusters.
AB  - Based on first-principles calculations of titanium oxide clusters, TinOm (n = 1
      4), we reveal the composition dependent reactivity of titanium oxide clusters.
      Our interesting results include: (1) the reactivity depends on the ratio of O
      atoms in the clusters, with smaller O ratios associated with higher reactivity;
      (2) among the different titanium oxide species investigated, the most stable
      structures are TinO2n, but their reactivities are relatively lower than the
      clusters with a smaller O atom ratio; moreover, (3) when the O atom ratio is
      small, the reactivity required to form the Ti-Ti bond is larger than either the
      Ti-O or O-O bond between two interacting titanium oxide clusters. These results
      will be useful for designing efficient titanium oxide catalysts, or
      photocatalysts, in particular, for energy and environmental applications. 

PMID- 27035361
TI  - Delphi Process in the Management of Pediatric Cataract.

PMID- 27035362
TI  - Selective partial hydrogenation of alkynes to (Z)-alkenes with ionic liquid-doped
      nickel nanocatalysts at near ambient conditions.
AB  - A selective hydrogenation method for forming (Z)-alkenes from alkynes has been
      developed using a catalyst system of cheap Ni-NPs in a nitrile functionalised
      imidazolium based ionic liquid (IL) operating under very mild reaction conditions
      of 30-50  degrees C and 1-4 bar H2 pressure. 

PMID- 27035363
TI  - Stereotactic body radiation therapy for low and intermediate risk prostate cancer
      Results from a multi-institutional clinical trial.
AB  - BACKGROUND: We report the outcome of a phase I/II clinical trial of stereotactic
      body radiation therapy (SBRT) for low (LR) and select intermediate risk (IR)
      prostate cancer (PCa) patients. PATIENTS AND METHODS: Eligible patients included
      men with prostate adenocarcinoma with Gleason score 6 with PSA <= 20 or Gleason 7
      with PSA <= 15 and clinical stage <= T2b. For the phase I portion of the study
      patients in cohorts of 15 received 45, 47.5, or 50 Gray (Gy) in five fractions.
      Since the maximally tolerated dose was not met in the phase I study, an
      additional 47 patients received 50 Gy in five fractions in the phase II study.
      Toxicity using Common Toxicity Criteria for Adverse Events v. 3.0, quality of
      life, and outcome data was collected. RESULTS: A total of 91 patients are
      included for analysis; 63.7% had NCCN IR and 36.3% had LR PCa. At a median follow
      up of 54 months the actuarial freedom from biochemical failure was 100% at 3
      years and 98.6% at 5 years. Actuarial distant metastasis free survival was 100%
      at 3 and 5 years. Overall survival was 94% at 3 years and 89.7% at 5 years with
      no deaths attributed to PCa. Acute and late urinary grade >= III toxicity
      occurred in 0% and 5.5% of patients, respectively. Gastrointestinal (GI) acute
      and late toxicity of grade >= III occurred in 2% and 7% of patients,
      respectively. A total of four men experienced grade IV toxicity (three GI, one
      genitourinary). CONCLUSION: SBRT treatment results in excellent biochemical
      control rates at 5 years for LR and IR PCa patients although doses greater than
      47.5 Gy in five fractions led to increased severe late toxicity.

PMID- 27035364
TI  - Response to "Comment on 'Effects of Atrazine on Estrogen Receptor <- and G
      Protein-Coupled Receptor 30-Mediated Signaling and Proliferation in Cancer Cells
      and Cancer-Associated Fibroblasts'".

PMID- 27035365
TI  - The Influence of the Two World Wars on the Development of Rehabilitation for
      Spinal Cord Injuries in the United States and Great Britain.
AB  - During World War I, physical and occupational therapies became important adjuncts
      to surgical practice, particularly for orthopedic casualties, but there was
      little progress in the management of severe brain and spinal cord injuries
      (SCIs), largely because of the very high mortality of such injuries at that time.
      During World War II (WWII), rehabilitation was greatly expanded into an
      integrated, comprehensive multidisciplinary program in the U.S. military, largely
      because of the efforts of Howard Rusk (1901-1989), initially in the Army Air
      Corps and later across all of the services. With Bernard Baruch's (1870-1965)
      assistance, Rusk was also successful in swaying President Franklin Delano
      Roosevelt (1882-1945) to support rehabilitation for injured veterans and to give
      official standing to rehabilitation medicine in the military and the Veterans
      Administration after WWII. Such WWII developments in rehabilitation medicine had
      a profound effect on the care, functional outcomes, and survival of veterans with
      SCIs. Neurosurgeon Donald Munro's (1898-1978) prototype SCI unit at Boston City
      Hospital in 1936 influenced the U.S. Army to establish several SCI centers during
      WWII and influenced urologist Ernest Bors (1900-1990) to pioneer SCI care in
      Veterans Administration medical centers after WWII. In Britain, the
      organizational leadership of George Riddoch (1888-1947) led to the development of
      SCI units that saw their greatest development by Ludwig Guttmann (1899-1980) at
      Stoke-Mandeville Hospital in Aylesbury, near London. These SCI centers provided a
      comprehensive spectrum of care, including medical, neurological, and surgical
      management; psychological counseling; and rehabilitation focused on improving
      self-care, mobility, and re-assimilation into society. After WWII, military
      developments in comprehensive rehabilitation were promulgated to and developed in
      the revitalized Veterans Administration and then disseminated to civilian
      populations. 

PMID- 27035366
TI  - Differences in the structure and functioning of two communities: Frondose and
      turf-forming macroalgal dominated habitats.
AB  - In many coastal regions, vegetated habitats (e.g. kelps forests, seagrass beds)
      play a key role in the structure and functioning of shallow subtidal reef
      ecosystems, by modifying local environmental conditions and by providing food and
      habitat for a wide range of organisms. In some regions of the world, however,
      such idiosyncratic ecosystems are largely absent and are often replaced by less
      notable ecosystem formers. In the present study, we empirically compared the
      structure and functioning of two distinct shallow-water habitats present in the
      Azores: one dominated by smaller frondose brown macroalgae (Dictyotaceae and
      Halopteris) and one dominated by low-lying turfs. Two replicated areas of each
      habitat were sampled at two different times of the year, to assess spatial and
      temporal consistency of results. Habitats dominated by small fronds were
      significantly (ca. 3 times) more productive (when standardized per algal mass)
      compared to the turf-dominated habitats, and supported a distinct assemblage
      (both in terms of composition and abundance) of associated macrofauna. Unlike
      other well-known and studied vegetated habitats (i.e. kelp forests), however, no
      effects of habitat were found on the structure of benthonic fish assemblages.
      Results were spatially and temporally consistent suggesting that, in warmer
      temperate oceans, habitats dominated by species of smaller frondose brown algae
      can also play an important role in the structure and functioning of subtidal
      communities and may, to a certain extent, be considered analogous to other well
      known vegetated habitats around the world (i.e. kelp forests, seagrass beds). 

PMID- 27035367
TI  - The Role of Platelets in Chronic Urticaria.
AB  - BACKGROUND: Platelets are implicated in many pathophysiological processes,
      including inflammation and immunity. Ever-growing evidence suggests the active
      involvement of platelets in the pathogenesis of various inflammatory disorders,
      including cutaneous inflammatory diseases. A limited number of studies have
      investigated the role of platelets in chronic urticaria (CU). In this review, we
      summarize the current knowledge regarding the role of platelets in chronic
      spontaneous and inducible urticarias. METHODS: A literature search was performed
      using PubMed and Google Scholar, and the references of relevant literature were
      reviewed. RESULTS: Overall, in CU patients, conflicting results have been
      obtained from the assessment of platelet indices, such as mean platelet volume,
      platelet count and distribution width, as well as markers of platelet aggregation
      and activation. Nevertheless, a few studies showed significant changes of such
      parameters in CU patients compared to controls, in apparent correlation with
      clinical severity, autoreactivity and/or inflammatory status. CONCLUSIONS: In the
      absence of definitive conclusions, the pathogenic role of platelets in CU needs
      to be further explored. Platelets might represent a link between inflammation,
      coagulation and histamine release in the pathophysiological network of CU.

PMID- 27035368
TI  - DEER Sensitivity between Iron Centers and Nitroxides in Heme-Containing Proteins
      Improves Dramatically Using Broadband, High-Field EPR.
AB  - This work demonstrates the feasibility of making sensitive nanometer distance
      measurements between Fe(III) heme centers and nitroxide spin labels in proteins
      using the double electron-electron resonance (DEER) pulsed EPR technique at 94
      GHz. Techniques to measure accurately long distances in many classes of heme
      proteins using DEER are currently strongly limited by sensitivity. In this paper
      we demonstrate sensitivity gains of more than 30 times compared with previous
      lower frequency (X-band) DEER measurements on both human neuroglobin and sperm
      whale myoglobin. This is achieved by taking advantage of recent instrumental
      advances, employing wideband excitation techniques based on composite pulses and
      exploiting more favorable relaxation properties of low-spin Fe(III) in high
      magnetic fields. This gain in sensitivity potentially allows the DEER technique
      to be routinely used as a sensitive probe of structure and conformation in the
      large number of heme and many other metalloproteins. 

PMID- 27035369
TI  - Futility and the Alluring Fantasy of Avoiding Conflict.

PMID- 27035370
TI  - Altered KATP Channel Subunits Expression and Vascular Reactivity in Spontaneously
      Hypertensive Rats With Age.
AB  - ATP-sensitive potassium (KATP) channels link membrane excitability to metabolic
      state to regulate a series of biological activities including the vascular tone.
      However, their ability to influence hypertension is controversial. Here we aim to
      investigate possible alteration of KATP channel in vascular smooth muscles (VSMs)
      during hypertension development process. In this study, we used 16-week-old
      spontaneously hypertensive rats (SHRs), 49-week-old SHRs, and their age-matched
      Wistar-Kyoto rats to study the expression of VSM KATP subunits at the mRNA and
      protein level and the function of VSM KATP by observing the relaxation reactivity
      of isolated aorta rings to KATP modulators. We found that the expression of VSM
      KATP subunits Kir6.1 and sulfonylurea receptor (SUR2B) decreased during
      hypertension. Moreover, the expression of SUR2B and Kir6.1 in 49-week-old SHRs
      decreased much more than that in 16-week-old SHRs. Furthermore, the aorta rings
      of 49-week-old SHRs showed lower reactivity to diazoxide than 16-week-old SHRs.
      This study suggests that KATP channels in VSM subunits Kir6.1 and SUR2B
      contribute to modify the functionality of this channel in hypertension with age. 

PMID- 27035371
TI  - Effect of Formula Containing Lactobacillus reuteri DSM 17938 on Fecal Microbiota
      of Infants Born by Cesarean-Section.
AB  - OBJECTIVES: Microbiota modulation by probiotics in infants born by cesarean (C)
      section is poorly understood. We aimed at assessing the response of C-section
      delivered infant microbiota to a formula containing Lactobacillus reuteri
      Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 and
      comparing it with that of vaginally delivered infants. METHODS: Infants delivered
      by C-section (C) and vaginally (V) were randomized to receive either control
      formula (CCt, n = 10; VCt, n = 10) or the same formula containing L reuteri (CLr,
      n = 11; VLr, n = 9) within 72 hours following birth. Stool samples were collected
      at 2 weeks and 4 months of age. Microbial DNA was extracted, amplified, and
      pyrosequenced. RESULTS: The phylogenetic profiles of the CLr, VCt, and VLr
      microbiota were not significantly different at any age but diverged from that of
      CCt at 2 weeks. Compared with VCt, CCt displayed lower Bifidobacterium and higher
      Enterobacter, unclassified Enterobacteriaceae, Enterococcus, Clostridium, and
      unclassified Clostridiaceae relative abundance at 2 weeks, as well as lower
      Collinsella and higher Enterococcus and Coprococcus abundance at 4 months. The
      level of most of these taxa was not significantly different between the CLr and
      the vaginal-delivery groups. Compared with VCt, the only difference observed in
      VLr microbiota was higher Lactobacillus at the 2 study ages and Coprococcus at 4
      months. CONCLUSIONS: Our results show that a formula containing L reuteri DSM
      17938 does not essentially alter the microbiota in vaginally born infants. In C
      section-delivered infants, however, this strain seems to play the role of
      keystone species by modulating the early development of the microbiota toward the
      composition found after vaginal delivery.

PMID- 27035374
TI  - NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related
      Disorders.
AB  - Dietary exclusion of gluten-containing products has become increasingly popular
      in the general population, and currently ~30% of people in the United States are
      limiting gluten ingestion. Although celiac disease (CD), wheat allergy (WA), and
      nonceliac gluten sensitivity (NCGS) constitute a spectrum of gluten-related
      disorders that require exclusion of gluten from the diet, together these account
      for a relatively small percentage of those following a gluten-free diet, and the
      vast majority has no medical necessity for doing so. Differentiating between CD,
      WA, and NCGS has important prognostic and therapeutic implications. Because of
      the protean manifestations of gluten-related disorders, it is not possible to
      differentiate between them on clinical grounds alone. This clinical report will
      compare and contrast the manifestations of gluten-related disorders, emphasize
      the importance of differentiating between these conditions, discuss initial and
      subsequent tests needed to confirm the diagnosis, and provide recommendations on
      treatment and follow-up for each condition.

PMID- 27035372
TI  - Effect of Psychotherapy on Health Care Utilization in Children With Inflammatory
      Bowel Disease and Depression.
AB  - OBJECTIVES: Pediatric patients with inflammatory bowel disease (IBD) are at an
      increased risk of developing depression compared with community controls.
      Depression often negatively influences illness behaviors such as resource
      utilization. We sought to investigate the effects of treating depression on
      utilization of medical resources in depressed pediatric patients with IBD by
      comparing rates of health care utilization 1 year before and after psychotherapy.
      METHOD: Two hundred seventeen subjects ages 9 to 17 years with IBD and depression
      received 3 months of psychotherapy for depression as part of a multicenter
      randomized controlled trial. Of these 217 subjects, 70 had utilization data
      available 1 year prior and 1 year after receiving 3 months of psychotherapy.
      Primary outcomes included frequency of hospitalizations, inpatient hospital days,
      outpatient gastrointestinal visits, and number of emergency room visits,
      radiological examinations, and endoscopies. Within subject analyses were
      completed comparing health care utilization 12 months before psychotherapy
      compared with the 12 months after the conclusion of psychotherapy. RESULTS: Fifty
      one and 19 patients had CD and UC, respectively. A total of 55.7% of patients had
      major depression and 44.3% had minor depression. Overall, all study measures of
      health care utilization were significantly reduced after psychotherapy (P < 0.01)
      including gastrointestinal-related (mean values) hospitalization frequency,
      inpatient days, outpatient visit, emergency room visits, radiological
      examinations, and endoscopies. CONCLUSIONS: Psychotherapy for comorbid depression
      in pediatric patients with IBD is associated with decreased GI-related health
      care utilization. The present study highlights the importance of screening for
      depression in a pediatric population with IBD, and that psychotherapy may be a
      reasonable adjunctive treatment for pediatric patients with IBD and comorbid
      depression.

PMID- 27035376
TI  - Young ESPGHAN: Who Are We?

PMID- 27035377
TI  - Anemia in Pediatric Celiac Disease: Association With Clinical and Histological
      Features and Response to Gluten-free Diet.
AB  - GOALS: The aim of the present study was to compare clinical, serological, and
      histological manifestations between children with anemia and without anemia at
      celiac disease (CD) diagnosis. BACKGROUND: Despite being a common finding, the
      association between the presence of anemia and clinicohistopathological
      presentation of CD in children remains obscure. STUDY: A total of 455 patients
      with CD <18 years of age were divided into those with anemia and those without
      anemia at diagnosis. The groups underwent comparisons of a variety of clinical,
      serological, and laboratory parameters and severity of small-bowel mucosal
      damage. Furthermore, adherence and clinical and serological response to the
      gluten-free diet (GFD) were compared. RESULTS: Anemia was detected in 18.0% of
      the patients. Children with anemia had higher values for transglutaminase 2
      antibodies (120.0 U/L vs 88.0 U/L, P < 0.001) and, by definition, lower values
      for hemoglobin (10.5 g/dL vs 12.8 g/dL, P < 0.001) and other iron parameters.
      They were also less often screen-detected (13.4% vs 34.6%), had more severe
      histological damage (P = 0.048), and poorer dietary adherence (78.3% vs 87.5%, P
      = 0.035) than the patients without anemia. A total of 92% of the patients
      recovered from anemia after a median of 1 year on a GFD, but hemoglobin values
      remained significantly lower compared with the nonanemic group (12.5 g/dL vs 13.2
      g/dL, P = 0.045). There was no difference between the groups in the clinical and
      serological response to the GFD (P = 0.318). CONCLUSIONS: Anemia at CD diagnosis
      is associated with more severe histological and serological presentation in
      children. Furthermore, low hemoglobin may not fully recover even after a median
      of 1 year on a strict GFD.

PMID- 27035378
TI  - Reply to a Letter to the Editor Regarding the Original Article, Clinical Features
      of Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2015;61(6):
      619-625.

PMID- 27035379
TI  - Preschoolers With Allergic Diseases Have an Increased Risk of Irritable Bowel
      Syndrome When Reaching School Age.
AB  - OBJECTIVES: The aim of the study was to systemically investigate the risk of
      subsequent irritable bowel syndrome (IBS) in children with antecedent allergic
      diseases in a population-based case-control study in Taiwan. METHODS: We
      evaluated 11,242 children (age range: 7-18 years) with IBS and 44,968 age- and
      sex-matched control subjects who had been examined between 2000 and 2008. IBS
      odds ratios were calculated for children with antecedent allergic diseases,
      including allergic conjunctivitis, allergic rhinitis, asthma, atopic dermatitis,
      urticaria, and food allergy. RESULTS: Children with antecedent allergic diseases
      had a greater risk of IBS than did control subjects (P < 0.001). Among the 6
      evaluated diseases, the highest adjusted odds ratio of 1.78 was observed with
      allergic rhinitis (95% confidence interval [CI], 1.69-1.87). With 2 or more
      allergic diseases, the adjusted odds ratios increased to 2.06 (95% CI, 1.93-2.19)
      for all subjects, 2.07 (95% CI, 1.88-2.28) for girls, and 2.18 (95% CI, 2.02
      2.35) for children 12 years or older. CONCLUSIONS: Preschoolers with a history of
      allergic disease had an increased risk of subsequent IBS development upon
      reaching school age. This risk increased in the presence of concurrent allergic
      disease and a higher clinical allergy burden.

PMID- 27035380
TI  - Accuracy of a Genetic Test for the Diagnosis of Hypolactasia in Chilean Children:
      Comparison With the Breath Test.
AB  - BACKGROUND: Lactase nonpersistence (LNP) in humans is a genetically determined
      trait. This age-dependent decrease of lactase expression is most frequently
      caused by single nucleotide polymorphisms in the regulatory region of the lactase
      (LCT) gene. The homozygous LCT-13,910C/C genotype (rs 4988235) predominates in
      Caucasian adults with LNP, and is useful for its diagnosis in this population.
      The accuracy of this genetic test (GT) has not been completely established in
      children or in a Latin-American population. OBJECTIVES: The aim of the study was
      to determine diagnostic accuracy of GT for LNP in Chilean children using the
      lactose breath test (BT) as a reference, and to compare diagnostic yield in
      preschool- (<6 years) and in school-age (>=6 years) children. METHODS: Children
      referred for BT for diagnosis of lactose malabsorption to the Gastroenterology
      Laboratory at Clinica Alemana, Santiago, from October 2011 to March 2012 were
      invited to participate. After informed consent, symptom questionnaires, both
      historic and post lactose ingestion were completed. H2 and CH4 in expired air and
      -13,910 C>T single nucleotide polymorphism by polymerase chain reaction,
      restriction enzyme analysis, and/or Sanger sequencing were determined. GT
      accuracy was calculated compared to BT as reference method. Diagnostic yield of
      GT in preschool- and school-age children was compared. RESULTS: Lactose
      malabsorption was detected by BT in 42 of 60 children (70%). Genotype -13,910C/C
      was identified in 41 of 60 patients (68%). GT showed 80% sensitivity, 63%
      specificity, and 74% accuracy for LNP in the preschool population. In school-age
      children values were higher, 85%, 80%, and 84%, respectively. CONCLUSIONS: GT
      results were significantly concordant with BT results for hypolactasia detection
      in Chilean children, particularly in those of age 6 years and older.

PMID- 27035381
TI  - Mode of Delivery Determines Neonatal Pharyngeal Bacterial Composition and Early
      Intestinal Colonization.
AB  - OBJECTIVES: Bacterial colonization and succession of the human intestine shape
      development of immune function and risk for allergic disease, yet these processes
      remain poorly understood. We investigated the relations between delivery mode,
      initial bacterial inoculation of the infant oropharynx (OP), and intestinal
      colonization. METHODS: We prospectively collected maternal rectal and vaginal
      swabs, infant OP aspirates, and infant stool from 23 healthy mother/infant pairs
      delivering by cesarean (CS) or vaginal delivery (VD) in an academic hospital.
      Bacterial abundance (16S rRNA sequencing) and community similarity between
      samples were compared by delivery mode. Shotgun DNA metagenomic sequencing of
      infant stool was performed. RESULTS: VD infants had higher abundance of
      Firmicutes (mainly lactobacilli) in OP aspirates whereas CS OP aspirates were
      enriched in skin bacteria. OP aspirates were more similar to maternal vaginal and
      rectal microbiomes in VD compared with CS. Bacteroidetes were more abundant
      through 6 weeks in stool of VD infants. Infant fecal microbiomes in both delivery
      groups did not resemble maternal rectal or vaginal microbiomes. Differences in
      fecal bacterial gene potential between CS and VD at 6 weeks clustered in
      metabolic pathways and were mediated by abundance of Proteobacteria and
      Bacteroidetes. CONCLUSIONS: CS infants exhibited different microbiota in the oral
      inoculum, a chaotic pattern of bacterial succession, and a persistent deficit of
      intestinal Bacteroidetes. Pioneer OP bacteria transferred from maternal vaginal
      and intestinal communities were not prominent constituents of the early infant
      fecal microbiome. Oral inoculation at birth may impact the intestinal
      microenvironment, thereby modulating early succession of intestinal bacteria.

PMID- 27035382
TI  - The fungicide imazalil induces developmental abnormalities and alters locomotor
      activity during early developmental stages in zebrafish.
AB  - The fungicide imazalil (IMZ) is used extensively to protect vegetable fields,
      fruit plantations and post-harvest crops from rot. Likely due to its wide-spread
      use, IMZ is frequently detected in vegetable, fruit, soil and even surface water
      samples. Even though several previous studies have reported on the neurotoxicity
      of IMZ, its effects on the neurobehavior of zebrafish have received little
      attention to date. In this study, we show that the heartbeat and hatchability of
      zebrafish were significantly influenced by IMZ concentrations of 300 MUg L(-1) or
      higher. Moreover, in zebrafish larvae, locomotor behaviors such as average
      swimming speed and swimming distance were significantly decreased after exposure
      to 300 MUg L(-1) IMZ for 96 h, and acetylcholinesterase (AChE) expression and
      activity were consistently inhibited in IMZ-treated fish. Our results further
      suggest that IMZ could act as a neuroendocrine disruptor by decreasing the
      expression of neurotoxicity-related genes such as Glial fibrillary acidic protein
      (Gfap), Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early
      developmental stages of zebrafish. In conclusion, we show that exposure to IMZ
      has the potential to induce developmental toxicity and locomotor behavior
      abnormalities during zebrafish development.

PMID- 27035383
TI  - The involvement of the mitochondrial pathway in manganese-induced apoptosis of
      chicken splenic lymphocytes.
AB  - The purpose of this study was to investigate the effect of excess manganese (Mn)
      induced cytotoxicity on apoptosis in chicken splenic lymphocytes. Chicken splenic
      lymphocytes were cultured in medium in the absence and presence of manganese (II)
      chloride (MnCl2) (2 * 10(-4), 4 * 10(-4), 6 * 10(-4), 8 * 10(-4), 10 * 10(-4),
      and 12 * 10(-4) mM), in N-acetyl-l-cysteine (NAC) (1 mM), and the combination of
      MnCl2 and NAC for 12, 24, 36, and 48 h. Tests were performed on morphologic
      observation, reactive oxygen species (ROS) and malondialdehyde (MDA) content,
      manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase (GSH-Px)
      activities, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), p53, and
      calmodulin (CaM) messenger RNA (mRNA) expression, Caspase-3 mRNA and protein
      expression, intracellular free Ca(2+) ([Ca(2+)]i), and mitochondrial
      transmembrane potential (DeltaPsim). Our research indicated that excess Mn
      induced ROS and MDA content, inhibited Mn-SOD and GSH-Px activities, induced Bax
      and p53 mRNA expression, inhibited Bcl-2 and CaM mRNA expression, induced Caspase
      3 mRNA and protein expression, upregulated [Ca(2+)]i, inhibited DeltaPsim, and
      induced apoptosis in a dose effect. NAC relieved excess Mn-caused the changes of
      all above factors. Mn-induced oxidative injuries were alleviated by treatment
      with NAC, an ROS scavenger. The above results demonstrated that excess Mn caused
      oxidative stress and apoptosis via mitochondrial pathway in chicken splenic
      lymphocytes.

PMID- 27035384
TI  - Phosphate fertilizer impacts on glyphosate sorption by soil.
AB  - This research examined the impact of field-aged phosphate and cadmium (Cd)
      concentrations, and fresh phosphate co-applications, on glyphosate sorption by
      soil. Soil samples were collected in 2013 from research plots that had received,
      from 2002 to 2009, annual applications of mono ammonium phosphate (MAP) at 20, 40
      and 80 kg P ha(-1) and from products containing 0.4, 70 or 210 mg Cd kg(-1) as an
      impurity. A series of batch equilibrium experiments were carried out to quantify
      the glyphosate sorption distribution constant, Kd. Extractable Cd concentrations
      in soil had no significant effect on glyphosate sorption. Glyphosate Kd values
      significantly decreased with increasing Olsen-P concentrations in soil,
      regardless of the pH conditions studied. Experiments repeated with a commercially
      available glyphosate formulation showed statistically similar results as the
      experiments performed with analytical-grade glyphosate. Co-applications of MAP
      with glyphosate also reduced the available sorption sites to retain glyphosate,
      but less so when soils already contain large amounts of phosphate. Glyphosate Kd
      values in soils ranged from 173 to 939 L kg(-1) under very strong to strongly
      acidic condition but the Kd was always <100 L kg(-1) under moderately acidic to
      slightly alkaline conditions. The highest Olsen-P concentrations in soil reduced
      Kd values by 25-44% relative to control soils suggesting that, under moderately
      acidic to slightly alkaline conditions, glyphosate may become mobile by water in
      soils with high phosphate levels. Otherwise, glyphosate residues in agricultural
      soils are more likely to be transported off-site by wind and water-eroded
      sediments than by leaching or runoff.

PMID- 27035385
TI  - Exchange of organohalogen compounds between air and tree bark in the Yellow River
      region.
AB  - Organohalogen compound concentrations in paired air and bark samples from the
      Yellow River region were determined. Overall, the organohalogen compound
      concentrations were higher in the samples from the lower than from the upper
      Yellow River region. The polybrominated diphenyl ether, polychlorinated biphenyl,
      and organochlorine pesticide concentrations were 310-5200, 0.92-3.8, and 120-6700
      pg m(-3), respectively, in the air samples and 29,000-190,0000, 220-1400, and
      49,000-220,0000 pg g(-1) lipid weight, respectively, in the bark samples. The
      concentrations in the air samples were significantly positively correlated with
      the concentrations in the bark samples. Constant B, related to the partitioning
      of a contaminant between the gas and particle phases in the air, was calculated
      for each compound. This was the first time constant B was simultaneously been
      determined for a range of different organohalogen compounds. An air-tree bark
      exchange model was calibrated and verified. The exchange coefficients (K(BA))
      that were determined were compared with the model results, and the optimum K(OA)
      values for use in the model were found to be 10(9)-10(16). The compound of
      interest needed to be detected in more than 50% of the samples for the model
      results to be valid.

PMID- 27035386
TI  - Toluene diisocyanate based phase-selective supramolecular oil gelator for
      effective removal of oil spills from polluted water.
AB  - Due to tremendous resource wastes and great harm to ecological environment caused
      by the accidental oil spills, an alkyl bicarbamate supramolecular oil gelator was
      synthesized and applied to selectively gelate oils from oil/water mixtures.
      Interestingly, the oil gelator could be self-assembled in a series of organic
      solvents, i.e., edible oils and fuel oils to form 3D networks and then turned
      into thermally reversible organogels, allowing easy separation and removal of oil
      spills from oil/water mixtures. The possible self-assembly mode for the formation
      of organogels was proposed. What's more, the optimal conditions for using the oil
      gelator to recover oils were experimentally determined. Inspiringly, taking
      gasoline as the co-congealed solvent, a complete gelation of oil phase was
      achieved within 15 min with high oil removal rate and oil retention rate after
      convenient salvage and cleanup of oil gels from oil/water mixtures. The oil
      gelator had some advantages in solidifying oil spills on water surface,
      exhibiting fast oil gelation, convenient and thorough oil removal and easy
      recovery. This work illustrates the significant role of oil gelators in the
      potential cleanup of spilled oils for water purification.

PMID- 27035387
TI  - Photochemical transformation of sunscreen agent benzophenone-3 and its metabolite
      in surface freshwater and seawater.
AB  - The occurrence of sunscreen agents and their metabolites in surface waters gives
      rise to public concerns. However, little is known about the environmental fate of
      these pollutants at present, especially for their metabolites. In this study, we
      investigated the photochemical of sunscreen agents and their metabolites in
      natural waters, adopting benzophenone-3 (BP-3) and its human metabolite 4
      hydroxybenzophenone (4-OH-BP3) as examples. Results show that only anionic forms
      of both BP-3 and 4-OH-BP3 can undergo direct photodegradation. The photolytic
      rates of both compounds in natural waters are faster as compared to those in pure
      water. Radical scavenging experiments revealed that triplet-excited dissolved
      organic matter ((3)DOM(*)) was responsible for the indirect photodegradation of
      BP-3 and 4-OH-BP3 in seawater, whereas in freshwater, the indirect
      photodegradation of these two compounds was attributed to (3)DOM(*) and .OH.
      (1)O2 plays a negligible role in their photodegradation because of the weak (1)O2
      reactivity. Furthermore, we probed the contribution of .OH and (3)DOM(*) to the
      photodegradation of both compounds in freshwater, and the results revealed that
      .OH accounted for 56% and 59% of the observed photodegradation for BP-3 and 4-OH
      BP3, respectively, whereas (3)DOM(*) accounted for 43% and 12% of the observed
      photodegradation for BP-3 and 4-OH-BP3, respectively. These results are helpful
      in assessing the ecological risk of BP-3 and its metabolite in the aquatic
      environment.

PMID- 27035388
TI  - Effect of temperature downshifts on a bench-scale hybrid A/O system: Process
      performance and microbial community dynamics.
AB  - Effect of temperature downshifts on process performance and bacterial community
      dynamics was investigated in a bench-scale hybrid A/O system treating real
      domestic wastewater. Results showed that the average COD removal in this system
      reached 90.5%, 89.1% and 90.3% for Run 1 (25  degrees C), Run 2 (15  degrees C)
      and Run 3 (10  degrees C), respectively, and variations in temperature barely
      affected the effluent COD concentration. The average removal efficiencies of
      NH4(+)-N were 98.4%, 97.8%, 95.7%, and that of TN were 77.1%, 61.8%, 72% at 25 
      degrees C, 15  degrees C and 10  degrees C, respectively. Although the hybrid
      system was subjected to low temperature, this process effectively removed NH4(+)
      N and TN even at 10  degrees C with the average effluent concentrations of 2.4
      mg/L and 14.3 mg/L, respectively. Results from high-throughput sequencing
      analysis revealed that when the operation temperature decreased from 25  degrees
      C to 10  degrees C, the richness and diversity indexes of the system decreased in
      the sludge samples, while underwent an increase in the biofilm samples.
      Furthermore, the major heterotrophic bacteria consisted of Lewinella, Lutimonas,
      Chitinophaga and Fluviicola at 10  degrees C, which could be central to effective
      COD removal at low temperature. Additionally, Azospira, one denitrifying-related
      genus increased from 0.4% to 4.45% in the biofilm samples, with a stable TN
      removal in response to temperature downshifts. Nitrosomonas and Nitrospira
      increased significantly in the biofilm samples, implying that the attached
      biofilm contributed to more nitrification at low temperature.

PMID- 27035389
TI  - Electrochemical efficacy of a carboxylated multiwalled carbon nanotube filter for
      the removal of ibuprofen from aqueous solutions under acidic conditions.
AB  - This study provides insight into the efficiency of a functionalized multiwalled
      carbon nanotube filter for the removal of an anti-inflammatory drug, ibuprofen,
      through conventional filtration and electrochemical filtration processes. A
      comparison was made between carboxylated multiwalled carbon nanotubes (MWNTs
      COOH) and pristine multiwalled carbon nanotubes (MWNTs) in order to emphasize the
      enhanced performance of MWNTs-COOH for the removal of ibuprofen using an
      electrochemical filtration process under acidic conditions. Ibuprofen-removal
      trials were evaluated based on absorbance values obtained using a UV/Vis
      spectrophotometer, and possible degradation products were identified using liquid
      chromatography mass spectrometry (LC-MS). The results exhibited near complete
      removal of ibuprofen by MWNTs-COOH at lower applied potentials (2 V), at lower
      flow rates, and under acidic conditions, which can be attributed to the
      generation of superoxides and their active participation in simultaneous
      degradation of ibuprofen, and its by-products, under these conditions. At higher
      applied potential (3 V), the possible participation of both bulk indirect
      oxidation reactions, and direct electron transfer were hypothesized for the
      removal behavior over time (breakthrough). At 3 V under acidic conditions, near
      100% removal of the target molecule was achieved and was attributed to the
      enhanced generation of electroactive species toward bulk chemical reactions and a
      possible contribution from direct electron transfer under these conditions. The
      degradation by-products of ibuprofen were effectively removed by allowing longer
      residence time during the filtration process. Moreover, the effect of temperature
      was studied, yet showed a non-significant effect on the overall removal process.

PMID- 27035390
TI  - Gastrointestinal toxicities of first and second-generation small molecule human
      epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall
      cell lung cancer.

PMID- 27035391
TI  - Evaluation of blood-brain barrier-stealth nanocomposites for in situ glioblastoma
      theranostics applications.
AB  - The blood-brain barrier (BBB) is a physiological structure of the blood vessels
      in the brain. The BBB efficiently traps most therapeutic drugs in the blood
      vessels and stops them from entering the brain tissue, resulting in a decreased
      therapeutic efficiency. In this study, we developed BBB-stealth nanocomposites
      composed of iron oxide (Fe3O4) nanoparticles (NPs) as a safe nanocarrier for
      glioblastoma therapy. We showed the antitumor activity of Dox/alg-Fe3O4 NPs using
      in vitro and in vivo tests. We demonstrated that G23-alg-Fe3O4 NPs crossed the
      BBB and entered the brain. In situ glioblastoma tumor-bearing mice were used to
      successfully evaluate the antitumor activity of G23-Dox/alg-Fe3O4 NPs. Magnetic
      resonance imaging (MRI) and bioluminescence imaging (BLI) confirmed the BBB
      crossing. The BBB-stealth nanocomposites show great potential for a proof-of
      concept clinical trial as a theranostics platform for human brain tumor therapy. 

PMID- 27035392
TI  - Fast, Efficient, and Gentle Transfection of Human Adherent Cells in Suspension.
AB  - We demonstrate a highly efficient method for gene delivery into clinically
      relevant human cell types, such as induced pluripotent stem cells (iPSCs) and
      fibroblasts, reducing the protocol time by one full day. To preserve cell
      physiology during gene transfer, we designed a microfluidic strategy, which
      facilitates significant gene delivery in a short transfection time (<1 min) for
      several human cell types. This fast, optimized and generally applicable cell
      transfection method can be used for rapid screening of different delivery systems
      and has significant potential for high-throughput cell therapy applications. 

PMID- 27035393
TI  - Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen
      synthase kinase-3beta/beta-catenin signaling pathway.
AB  - The endogenous signaling gasotransmitter, hydrosulfide (H2S), has been shown to
      exert cardioprotective effects against acute myocardial infarction (AMI) due to
      ischemic injury. However, the mechanisms responsible for these effects are not
      yet fully understood. In this study, we investigated whether sodium hydrogen
      sulfide (NaHS), an H2S donor, attenuates acute myocardial ischemic injury through
      glycogen synthase kinase-3beta (GSK-3beta)/beta-catenin signaling. For this
      purpose, we utilized an in vivo rat model of AMI by occluding the left anterior
      descending coronary artery. NaHS (0.39, 0.78 or 1.56 mg/kg, intraperitoneally),
      the GSK-3beta inhibitor, SB216763 (0.6 mg/kg, intravenously), or 1%
      dimethylsulfoxide (2 ml/kg, intravenously) were administered to the rats. The
      results demonstrated that the administration of medium- and high-dose NaHS and
      SB216763 significantly improved rat cardiac function, as evidenced by an increase
      in the mean arterial pressure, left ventricular developed pressure, contraction
      and relaxation rates, as well as a decrease in left ventricular end-diastolic
      pressure. In addition, the administration of NaHS and SB216763 attenuated
      myocardial injury as reflected by a decrease in apoptotic cell death and in the
      serum lactate dehydrogenase concentrations, and prevented myocardial structural
      changes. The administration of NaHS and SB216763 increased the concentrations of
      phosphorylated (p-)GSK-3beta, the p-GSK-3beta/t-GSK-3beta ratio and downstream
      protein beta-catenin. Moreover, western blot and immunohistochemical analyses of
      apoptotic signaling pathway proteins further established the cardioprotective
      potential of NaHS, as reflected by the upregulation of Bcl-2 expression, the
      downregulation of Bax expression, and a decrease in the number of TUNEL-positive
      stained cells. These findings suggest that hydrosulfide exerts cardioprotective
      effects against AMI-induced apoptosis through the GSK-3beta/beta-catenin
      signaling pathway.

PMID- 27035394
TI  - The impact of personality on driving safety among Chinese high-speed railway
      drivers.
AB  - This study explored the impact of personality traits on driving safety in high
      speed railway drivers. A sample of high-speed railway drivers in Beijing (N=214)
      completed a questionnaire, including information on personality traits and
      background variables. The NEO Five Factor Inventory (NEO-FFI) was administered to
      characterize participants based on five personality traits: Neuroticism,
      Extraversion, Agreeableness, Openness to Experience, and Conscientiousness. The
      survey data were combined with naturalistic data of accident involvement and
      risky driving behavior in China. Poisson regression results show that drivers
      with high Conscientiousness and Extraversion caused fewer accidents. Higher
      Conscientiousness and lower Agreeableness were related to less frequent risky
      driving behavior. Education level and age negatively moderated the relation
      between certain personality traits and driving safety. The findings suggest that
      personality traits should be considered when selecting and training high-speed
      railway drivers. 

PMID- 27035395
TI  - Application of a random effects negative binomial model to examine tram-involved
      crash frequency on route sections in Melbourne, Australia.
AB  - Safety is a key concern in the design, operation and development of light rail
      systems including trams or streetcars as they impose crash risks on road users in
      terms of crash frequency and severity. The aim of this study is to identify key
      traffic, transit and route factors that influence tram-involved crash frequencies
      along tram route sections in Melbourne. A random effects negative binomial (RENB)
      regression model was developed to analyze crash frequency data obtained from
      Yarra Trams, the tram operator in Melbourne. The RENB modelling approach can
      account for spatial and temporal variations within observation groups in panel
      count data structures by assuming that group specific effects are randomly
      distributed across locations. The results identify many significant factors
      effecting tram-involved crash frequency including tram service frequency (2.71),
      tram stop spacing (-0.42), tram route section length (0.31), tram signal priority
      (-0.25), general traffic volume (0.18), tram lane priority (-0.15) and ratio of
      platform tram stops (-0.09). Findings provide useful insights on route section
      level tram-involved crashes in an urban tram or streetcar operating environment.
      The method described represents a useful planning tool for transit agencies
      hoping to improve safety performance. 

PMID- 27035396
TI  - Why drivers use cell phones and support legislation to restrict this practice.
AB  - The use of cell phones while driving is ubiquitous, particularly in countries
      where the practice is legal. However, surveys indicate that most drivers favor
      legislation to limit the use of mobile devices during the operation of a vehicle.
      A study was conducted to understand this inconsistency between what drivers do
      and what they advocate for others. Participants completed a survey about their
      driving attitudes, abilities, and behaviors. Following previous research, drivers
      reported using cell phones for benefits such as getting work done. The hypocrisy
      of using cell phones while advocating restrictions appears to stem from
      differences in the perceived safety risks of self vs. others' use of cell phones.
      Many if not most drivers believe they can drive safely while using mobile
      devices. However, they lack confidence in others' ability to drive safely while
      distracted and believe that others' use of cell phones is dangerous. The threat
      to public safety of others' usage of mobile devices was one of the strongest
      independent predictors of support for legislation to restrict cell phone use. 

PMID- 27035397
TI  - Circular RNAs as a new field in gene regulation and their implications in
      translational research.
AB  - Circular RNAs are a class of long noncoding RNA that were recently rediscovered
      as diverse, highly abundant, conserved and naturally occurring RNAs in
      eukaryotes. They are characterized by their 5' and 3' covalently joined ends.
      Some studies have attributed functions for circular RNAs, such as miRNAs sponges
      and transcriptional regulators, indicating that they may be largely biomarkers of
      both physiological and pathological processes. Circular RNAs have the potential
      to play important roles in transcription and post-transcription, giving rise to a
      whole complexity level to gene expression regulation. In this review, we discuss
      the biogenesis of circular RNAs, their properties and functions as well as
      different methods for their identification and their role in some diseases. 

PMID- 27035398
TI  - Opening the gateways to market and adoption of regenerative medicine? The UK case
      in context.
AB  - Regenerative medicine is a site for opposing forces of gatekeeping and
      innovation. This applies both to regulation of market entry and to clinical
      adoption. Key gateways include the EU's Advanced Therapy Medicinal Products
      Regulation, technology assessment body NICE and commissioning/service contractor
      National Health Service England. The paper maps recent gatekeeping flexibilities,
      describing the range of gateways to market and healthcare adoption seen as
      alternatives to mainstream routes. The initiatives range from exemptions in
      pharmaceutical and ATMP regulations, through 'adaptive pathways' and 'risk-based'
      approaches, to special designation for promising innovation, value-based
      assessment and commissioner developments. Future developments are considered in
      the UK's 'accelerated access review'. Caution is urged in assessing the impact of
      these gateway flexibilities and their market and public health implications. 

PMID- 27035399
TI  - The germline/soma dichotomy: implications for aging and degenerative disease.
AB  - Human somatic cells are mortal due in large part to telomere shortening
      associated with cell division. Limited proliferative capacity may, in turn, limit
      response to injury and may play an important role in the etiology of age-related
      pathology. Pluripotent stem cells cultured in vitro appear to maintain long
      telomere length through relatively high levels of telomerase activity. We propose
      that the induced reversal of cell aging by transcriptional reprogramming, or
      alternatively, human embryonic stem cells engineered to escape immune
      surveillance, are effective platforms for the industrial-scale manufacture of
      young cells for the treatment of age-related pathologies. Such cell-based
      regenerative therapies will require newer manufacturing and delivery technologies
      to insure highly pure, identified and potent pluripotency-based therapeutic
      formulations. 

PMID- 27035400
TI  - A female-biased sex ratio reduces the twofold cost of sex.
AB  - The evolution of sexual reproduction remains a fascinating enigma in biology.
      Theoretically, populations of sexual organisms investing half of their resources
      into producing male offspring that don't contribute to reproduction should grow
      at only half the rate of their asexual counterparts. This demographic
      disadvantage due to male production is known as the twofold cost of sex. However,
      the question of whether this cost is truly twofold for sexual females remains
      unanswered. The cost of producing males should decrease when the number of male
      offspring is reduced. Here, we report a case where the cost of males is actually
      less than twofold. By measuring the numbers of sexual strain coexisting with
      asexual strain among thrips, our survey revealed that the sexual strain showed
      female-biased sex ratios and that the relative frequency of sexual strain is
      negatively correlated with the proportion of males in the sexual strain. Using
      computer simulations, we confirmed that a female-biased sex ratio evolves in
      sexual individuals due to the coexistence of asexual individuals. Our results
      demonstrate that there is a cost of producing males that depends on the number of
      males. We therefore conclude that sexual reproduction can evolve with far fewer
      benefits than previously assumed. 

PMID- 27035401
TI  - Unresolved issues in lipid-lowering treatment.
AB  - Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major
      modifiable risk factor for cardiovascular disease (CVD). In addition, treatment
      with statins reduces cardiovascular morbidity and mortality both in patients
      without and with established CVD. However, there still exist unresolved issues in
      the management of dyslipidemia. First, which are the optimal LDL-C levels?
      Second, do low high-density lipoprotein cholesterol (HDL-C) levels play a role in
      the pathogenesis of atherosclerosis and should they also represent treatment
      targets? In the present review, we discuss these two pertinent questions.
      Accumulating data, both from observational studies and from interventional
      studies with statins and other lipid-lowering agents, suggest that lowering LDL-C
      levels considerably below the currently recommended targets is both safe and
      further reduces cardiovascular morbidity and mortality. These benefits are
      particularly relevant for patients at very high cardiovascular risk, i.e. those
      with established CVD. On the other hand, it is questionable whether HDL-C is
      causally related to atherosclerosis and whether increasing HDL-C levels will
      translate into reduced cardiovascular risk. This uncertainty is even more
      pronounced in patients who achieve very low LDL-C levels with statin treatment. 

PMID- 27035402
TI  - Elimination half-life of alpha-pyrrolidinovalerophenone in an acute non-fatal
      intoxication.

PMID- 27035403
TI  - Catalytic alcoholysis of epoxides using metal-free cucurbituril-based solids.
AB  - Metal-free cucurbit[7]uril (CB7) solid-state assemblies promote acid-catalysed
      alcoholysis of aliphatic and aromatic epoxides under mild conditions to give beta
      alkoxy alcohols, which are important intermediates for the synthesis of a vast
      range of compounds such as bioactive pharmaceuticals. The catalytic process is
      heterogeneous and the catalyst can be reused in consecutive runs without any
      reactivation treatment. The acid species responsible for the catalytic activity
      of CB7 may be entrapped hydronium ions. 

PMID- 27035404
TI  - Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as
      adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open
      label study following a placebo-controlled acute study.
AB  - OBJECTIVE: To evaluate remission and recovery, safety, and tolerability for up to
      12 months of open-label adjunctive L-methylfolate calcium 15 mg. METHOD: Subjects
      in this analysis were adult outpatients (18-65 years) enrolled from 2 acute,
      double-blind, placebo-controlled trials comparing adjunctive L-methylfolate and
      placebo for DSM-IV major depressive disorder (MDD) with an inadequate response to
      monotherapy selective serotonin reuptake inhibitor (SSRI). Subjects who completed
      the acute trial were offered to enroll in a 12-month, open-label treatment phase
      with L-methylfolate and continued SSRI treatment, with scheduled visits for
      efficacy, safety, and tolerability every 12 weeks. Subjects were enrolled between
      September 2006 and February 2010. Efficacy outcomes included predefined criteria
      for response, remission, recovery, relapse, and recurrence. Subjects treated with
      adjunctive L-methylfolate 15 mg were included in the efficacy analysis. RESULTS:
      Of 68 subjects who met criteria for the 12-month open-label phase, 38% (n = 26)
      achieved full recovery, and none experienced a recurrence of MDD. For subjects
      entering the open-label phase in remission (n = 11), 91% (n = 10) achieved full
      recovery with L-methylfolate 15 mg, and none experienced a relapse or recurrence.
      Among 57 subjects who entered the open-label phase as nonremitted, 61% (n = 35)
      achieved remission. Of subjects who entered the open-label phase with a response
      without remission (n = 4), 50% (n = 2) had full recovery, and of subjects
      entering the open-label phase with no response (n = 53), 26% (n = 14) met
      recovery criteria. CONCLUSIONS: Adjunctive L-methylfolate 15 mg/d may be an early
      option in patients who fail to adequately respond to antidepressant monotherapy,
      with preliminary evidence demonstrating sustained remission and sustained
      recovery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00321152.

PMID- 27035405
TI  - An asymmetrically dimethylarginated nuclear 90 kDa protein (p90aDMA) induced by
      interleukin (IL)-2, IL-4 or IL-6 in the tumor microenvironment is selectively
      degraded by autophagy.
AB  - Protein arginine methylation is a common posttranslational modification resulting
      in the generation of asymmetric dimethylarginine (aDMA) and symmetric
      dimethylarginine (sDMA). Currently, the regulation of aDMA or sDMA by hypoxia,
      nutrient stavation or cytokines in the tumor microenvironment remains largely
      unknown. Here we show that p90aDMA, p70aDMA and p90sDMA, endogenous proteins
      containing aDMA or sDMA with mass 70 or 90 kDa, were widely and dominantly
      expressed in breast cancer cell lines. Notably, it was p90aDMA rather than
      p90sDMA that accumulated in the nucleus upon stimulation of cancer cells with
      interleukin (IL)-2, IL-4, IL-6 but not IL-8. In addition, the p90aDMA
      accumulation could be inhibited after treatment with a global methyltrasferase
      inhibitor, adenosine-2',3'-dialdehyde (AdOx). It seemed that some endogenous
      proteins in cancer cells were asymmetrically arginine-methylated upon exposure to
      some cytokines.. Furthermore, endogenous proteins of aDMA, such as p90aDMA and
      p70aDMA, were degraded in response to hypoxia, nutrient starvation and rapamycin
      treatment in breast and cervical cancer cells. IL-2/4/6 slightly increased basal
      autophagy but slightly decreased the rapamycin-induced autophagy in cancer cells,
      suggesting that IL-2/4/6 and autophagy inducers play distinct roles in the
      regulation of aDMA of proteins. Conversely, rapamycin accumulated p90sDMA in MDA
      MB-231 and MCF-7 cells. Taken together, our results add a new dimension to the
      complexity of arginine methylated regulation in response to various stimuli and
      provide the first evidence that aDMA serves as one specific degradation signal of
      selective autophagy. 

PMID- 27035406
TI  - Fission of multiply charged alkali clusters in helium droplets - approaching the
      Rayleigh limit.
AB  - Electron ionization of helium droplets doped with sodium, potassium or cesium
      results in doubly and, for cesium, triply charged cluster ions. The smallest
      observable doubly charged clusters are Na9(2+), K11(2+), and Cs9(2+); they are a
      factor two to three smaller than reported previously. The size of sodium and
      potassium dications approaches the Rayleigh limit nRay for which the fission
      barrier is calculated to vanish, i.e. their fissilities are close to 1. Cesium
      dications are even smaller than nRay, implying that their fissilities have been
      significantly overestimated. Triply charged cesium clusters as small as Cs19(3+)
      are observed; they are a factor 2.6 smaller than previously reported. Mechanisms
      that may be responsible for enhanced formation of clusters with high fissilities
      are discussed.

PMID- 27035408
TI  - Eyes on New Product Development.

PMID- 27035407
TI  - Potential screening and early diagnosis method for cancer: Tongue diagnosis.
AB  - Tongue diagnosis, as a unique method of traditional Chinese medicine (TCM), was
      used to discriminate physiological functions and pathological conditions by
      observing the changes of the tongue and tongue coating. The aims of the present
      study were to explore a potential screening and early diagnosis method of cancer
      through evaluating the differences of the images of tongue and tongue coating and
      the microbiome on the tongue coating. The DS01-B tongue diagnostic information
      acquisition system was used to photograph and analyze the tongue and tongue
      coating. The next-generation sequencing technology was used to determine the V2
      V4 hypervariable regions of 16S rDNA to investigate the microbiome on the tongue
      coating. Bioinformatics and statistical methods were used to analyze the
      microbial community structure and diversity. Comparing with the healthy people,
      the number of mirror-like tongue, thick tongue coating and the moisture of tongue
      were increased in cancers. The dominant color of the tongue in the healthy people
      was reddish while it was purple in the cancers. The relative abundance of
      Neisseria, Haemophilus, Fusobacterium and Porphyromonas in the healthy people
      were higher than that in the cancers. We also found 6 kinds of special
      microorganisms at species level in cancers. The study suggested that tongue
      diagnosis may provide potential screening and early diagnosis method for cancer. 

PMID- 27035409
TI  - Hospitalizations and emergency department visits for psychiatric illness during
      and after pregnancy among women with schizophrenia.
AB  - BACKGROUND: Almost 50% of women with schizophrenia become pregnant. Little is
      known about their psychiatric service use patterns during or shortly after
      pregnancy. METHODS: Using health administrative data, we identified 1,433 women
      in Ontario, Canada, with schizophrenia (ICD-9, ICD-10, or DSM-IV-TR) who had a
      live birth delivery from January 2003 through March 2011 and described their use
      of acute psychiatric care services including hospitalizations, emergency
      department visits not requiring hospitalization, and self-harm-related emergency
      department visits during pregnancy and in the first year postpartum. Incidence
      rates of psychiatric hospitalization during pregnancy, and also within 1 year
      postpartum, were each compared to the incidence rate of psychiatric
      hospitalization in the 1-year period before conception. Results are presented as
      incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Similar
      comparisons were made for psychiatric emergency department visits not requiring
      hospitalization, as well as for self-harm-related emergency department visits.
      RESULTS: About 12% of the women had at least 1 psychiatric hospitalization during
      pregnancy, and 19% in the first year postpartum. About 10% had at least 1
      psychiatric emergency department visit without hospitalization during pregnancy,
      and 16% had at least 1 emergency department visit postpartum. Self-harm-related
      emergency department visits were rarer, affecting only about 1% of the women in
      each time period. Relative to that in the 1-year period before conception (50 per
      100 person-years), the incidence rate of psychiatric hospitalizations was lower
      during pregnancy (25 per 100 person-years), which is equivalent to an IRR of 0.50
      (95% CI, 0.43-0.60). While the IRR of psychiatric hospitalizations was lower over
      the entire 1-year period postpartum (0.66; 95% CI, 0.57-0.76), it was transiently
      higher in the first 9 days postpartum (3.59; 95% CI, 2.74-4.69) and then waned by
      days 10 to 29 postpartum (0.87; 95% CI, 0.56-1.24). Emergency department visits
      for psychiatric and self-harm reasons were consistently lower during pregnancy
      and postpartum compared to the year before conception. CONCLUSIONS: Psychiatric
      hospitalizations and emergency department visits are not uncommon for women with
      schizophrenia during pregnancy and the postpartum period. However, except for a
      brief period after delivery, women with schizophrenia are at relatively lower
      risk of requiring acute psychiatric inpatient and emergency care during and 1
      year after pregnancy compared to the 1-year period prior to conception. This is
      key prognostic information for women with schizophrenia, their families, and
      providers who counsel them regarding pregnancy, motherhood, and management of
      schizophrenia. Identifying women at risk of requiring acute psychiatric services
      in the perinatal period warrants further investigation.

PMID- 27035410
TI  - In situ MoS2 Decoration of Laser-Induced Graphene as Flexible Supercapacitor
      Electrodes.
AB  - Herein, we are reporting a rapid one-pot synthesis of MoS2-decorated laser
      induced graphene (MoS2-LIG) by direct writing of polyimide foils. By covering the
      polymer surface with a layer of MoS2 dispersion before processing, it is possible
      to obtain an in situ decoration of a porous graphene network during laser
      writing. The resulting material is a three-dimensional arrangement of
      agglomerated and wrinkled graphene flakes decorated by MoS2 nanosheets with good
      electrical properties and high surface area, suitable to be employed as
      electrodes for supercapacitors, enabling both electric double-layer and pseudo
      capacitance behaviors. A deep investigation of the material properties has been
      performed to understand the chemical and physical characteristics of the hybrid
      MoS2-graphene-like material. Symmetric supercapacitors have been assembled in
      planar configuration exploiting the polymeric electrolyte; the resulting
      performances of the here-proposed material allow the prediction of the enormous
      potentialities of these flexible energy-storage devices for industrial-scale
      production.

PMID- 27035411
TI  - Low-Cost Nanoribbon Sensors for Protein Analysis in Human Serum Using a Miniature
      Bead-Based Enzyme-Linked Immunosorbent Assay.
AB  - We describe a low cost thin-film transistor (TFT) nanoribbon sensor for detection
      of the inflammatory biomarker C-reactive protein (CRP) in human serum via a
      miniature bead-based enzyme-linked immunosorbent assay (ELISA). The TFT
      nanoribbon sensor measures the reaction products from the ELISA via pH changes.
      The bead-based ELISA decouples the protein functionalization steps from the
      sensor surface, increasing the signal and simplifying the assay. The ability to
      directly sense proteins in human serum in this way overcomes the Debye length
      limitation associated with nanowire and nanoribbon biosensors. Compared to
      classically fabricated nanowires, the TFT nanoribbon sensors are simple,
      extremely easy to fabricate, and should therefore be much cheaper to manufacture.
      TFT nanoribbon sensors, configured to measure pH, were used for quantitative
      detection of CRP spiked into human serum at concentrations as low as 0.2 ng/mL,
      which is 10 000 times lower than needed for diagnostic purposes, providing the
      potential for applications that require very high sensitivity.

PMID- 27035412
TI  - Temporal profiles of blood pressure, circulating nitric oxide, and adrenomedullin
      as predictors of clinical outcome in acute ischemic stroke patients.
AB  - Stroke remains an important health and social challenge. The present study
      investigated whether blood pressure (BP) parameters and circulating levels of
      nitric oxide metabolites (NOx) and adrenomedullin (AM) may predict clinical
      outcomes of stroke. Patients (n=76) diagnosed with acute ischemic stroke were
      admitted to the stroke unit and clinical history data and monitored parameters
      were recorded. Blood plasma was collected at days 1, 2, and 7 to measure NOx and
      AM levels. Infarct volume, neurological severity [on the National Institutes of
      Health Stroke Scale (NIHSS)], and functional prognosis (on the Rankin scale) were
      measured as clinical outcomes. Patients with higher BP had more severe symptoms
      (NIHSS >3; P<0.01) and BP variability predicted neurological severity and growth
      of infarct volume. NOx values were significantly lower in stroke patients than in
      healthy controls (P<0.01). An increase in NOx levels from day 1 to day 2 was
      beneficial for the patients as measured by NIHSS at 7 days and 3 months, and by
      Rankin at 3 months [odds ratio (OR), 0.91] whereas a steep increase from day 2 to
      day 7 was detrimental and associated with an increase in infarct volume (OR,
      35.3). AM levels were significantly higher in patients at day 1 and 2 than in
      healthy individuals (P<0.01) and these levels returned to normal at day 7.
      Patients with high AM levels at day 2 had significantly higher NIHSS scores
      measured at day 1 (P<0.05) and 7 (P<0.01). A receiving operating characteristic
      curve analysis identified that AM levels at day 2 of >522.13 pg/ml predicted
      increased neurological severity at day 7 (area under the curve=0.721).
      Multivariate logistic regression indicated that AM levels at day 2 predicted
      increased neurological severity at 7 days and at 3 months. BP parameters and
      changing levels for NOx and AM predicted long-term clinical outcomes as measured
      by infarct volume, neurological severity scale, and functional prognosis. 

PMID- 27035413
TI  - Effect of Recepteur d'Origine Nantais expression on chemosensitivity and tumor
      cell behavior in colorectal cancer.
AB  - Recepteur d'Origine Nantais (RON) expression is known to induce oncogenic
      properties including tumor cell growth, survival, motility, angiogenesis and
      chemoresistance. In the present study, we evaluated whether RON affects
      chemosensitivity and oncogenic behavior of colorectal cancer cells and
      investigated its prognostic value in colorectal cancer. To evaluate the impact of
      RON on chemosensitivity and tumor cell behavior, we treated colorectal cancer
      cells with small interfering RNAs specific to RON. This was followed by flow
      cytometric analyses and migration, Matrigel invasion and endothelial tube
      formation assays. The expression of RON was investigated by immunohistochemistry
      in colorectal cancer tissues. TUNEL assay and immunohistochemical staining for
      CD34 and D2-40 were deployed to determine apoptosis, angiogenesis and
      lymphangiogenesis. RON knockdown enhanced 5-fluorouracil (FU)-induced apoptosis
      by upregulating the activities of caspases and expression of proapoptotic genes.
      Moreover, it enhanced 5-FU-induced cell cycle arrest by decreasing the expression
      of cyclins and cyclin-dependent kinases and inducing that of p21. Furthermore,
      RON knockdown augmented the 5-FU-induced inhibition of invasion and migration of
      colorectal cancer cells. The beta-catenin signaling cascade was blocked by RON
      knockdown upon 5-FU treatment. RON knockdown also decreased endothelial tube
      formation and expression of VEGF-A and HIF-1alpha and increased angiostatin
      expression. Furthermore, it inhibited lymphatic endothelial cell tube formation
      and the expression of VEGF-C and COX-2. RON expression was observed to be
      associated with age, tumor size, lymphovascular and perineural invasion, tumor
      stage, lymph node and distant metastasis, and poor survival rate. The mean
      microvessel density value of RON-positive tumors was significantly higher than
      that of RON-negative ones. These results indicate that RON is associated with
      tumor progression by inhibiting chemosensitivity and enhancing angiogenesis in
      colorectal cancer. 

PMID- 27035414
TI  - A rare variant at 11p13 is associated with tuberculosis susceptibility in the Han
      Chinese population.
AB  - Genome-wide association studies (GWASs) have yet to be conducted for tuberculosis
      (TB) susceptibility in China. Two previously identified single nucleotide
      polymorphisms (SNPs) from tuberculosis GWASs, rs2057178 and rs4331426, were
      evaluated for TB predisposition. The associations between SNPs and gene
      expression levels were analyzed using the genomic data and corresponding whole
      genome expression of the Han Chinese in Beijing, China. Genotyping was
      successfully completed for 763 pulmonary TB patients and 763 healthy controls.
      The T allele of the rare variant rs2057178 was significantly associated with TB
      predisposition (chi(2) = 14.07, P = 0.0002). Meanwhile, the CT genotype of
      rs2057178 was associated with a decreased risk of TB (adjusted OR = 0.52, 95% CI,
      0.34-0.78). The CT genotype of rs2057178 was also associated with decreased
      expression levels of infection-related gene, suppressor of cytokine signaling 2
      (SOCS2), and increased expression levels of v-maf avian musculoaponeurotic
      fibrosarcoma oncogene homolog B (MAFB). No gene expression levels were found to
      be associated with the genotype of rs4331426. We found that the rare variant
      rs2057178 was significantly associated with TB in the Han Chinese population.
      Moreover, the expression levels of MAFB and SOCS2 correlated with rs2057178 and
      might be potential candidates for assessing TB susceptibility.

PMID- 27035416
TI  - N-Oxide as an Intramolecular Oxidant in the Baeyer-Villiger Oxidation: Synthesis
      of 2-Alkyl-2H-indazol-3-yl Benzoates and 2-Alkyl-1,2-dihydro-3H-indazol-3-ones.
AB  - In this study, we describe the intramolecular Baeyer-Villiger oxidation of
      ketones to esters using N-oxide. 2-Nitro-N-alkyl-N-(2-oxo-2
      phenylethyl)benzenesulfonamide compounds are known to undergo base-mediated C
      arylation followed by N-N bond formation, producing unstable five-membered ring
      intermediates that spontaneously dehydrate to indazole oxides. We identified the
      reaction conditions under which the cyclic intermediate undergoes acid-mediated
      intramolecular Baeyer-Villiger oxidation of the ketone in which N-oxide serves as
      the intramolecular oxidizing agent. The solid-phase synthesis plays a critical
      role in the successful transformation, allowing rapid access to the unstable but
      Baeyer-Villiger oxidation-prone intermediate. This synthetic route provides
      practical access to 2-alkyl-2H-indazol-3-yl benzoates and 2-alkyl-1,2-dihydro-3H
      indazol-3-ones, which are known privileged structures possessing remarkable
      diverse pharmacologically relevant activities.

PMID- 27035417
TI  - Inhibition of histone deacetylases by trans-cinnamic acid and its antitumor
      effect against colon cancer xenografts in athymic mice.
AB  - Previous studies have shown that trans-cinnamic acid (tCA) has a broad spectrum
      of biological activities, and exhibits antioxidant, anti-inflammatory and
      anticancer properties. In addition, tCA and a variety of its analogs have been
      detected as gut microbe-derived metabolites exerting various biological effects
      in the colon. The aim of this study was to assess the antitumor activity of tCA
      in vitro and in vivo, in particular its therapeutic efficacy against colon cancer
      xenografts in athymic mice. Furthermore, it aimed to examine the effects of tCA
      on histone deacetylases (HDACs) and to identify the underlying molecular
      mechanisms. Using an MTT assay, tCA was observed to inhibit the proliferation of
      several cancer cell lines, and the half maximal inhibitory concentration (IC50)
      in HT29 colon carcinoma cells was ~1 mM. Western blot analysis demonstrated that
      tCA upregulated the expression of acetyl-H3 and acetyl-H4 proteins, which was
      consistent with the effects of the HDAC inhibitor, trichostatin A (TSA).
      Furthermore, expression of Bcl-2 (a marker of cell proliferation) was reduced,
      and apoptosis was induced. Apoptosis was shown by the activation of cleavage of
      poly ADP ribose polymerase and the increased expression of Bax. Apoptosis was
      also confirmed using APC Annexin V and SYTOX Green Nucleic Acid Stain. In
      addition, the tCA-induced inhibition of the expression of HDAC markers and
      activation of apoptosis in tumor tissues were further confirmed by
      immunohistochemistry. Intragastric administration of tCA at doses of 1.0 and 1.5
      mmol/kg body weight suppressed the growth of HT29 human colon carcinoma
      xenografts in athymic mice at well-tolerated doses. No toxic changes were found
      in the heart, lung, liver, kidney, colon or bone marrow following
      histopathological examination. This study indicated that tCA is effective against
      colon cancer xenograft in nude mice. The antitumor mechanism of tCA was mediated,
      at least in part, by inhibition of HDACs in cancer cells. As an endogenous
      microbial metabolite predominantly produced in the colon, tCA is an agent of
      interest for further evaluation. 

PMID- 27035418
TI  - Sonic hedgehog-mediated epithelial-mesenchymal transition in renal
      tubulointerstitial fibrosis.
AB  - The sonic hedgehog (SHH) signaling pathway plays a critical role in embryonic
      development, tissue regeneration and organogenesis. The activation of SHH
      signaling produces profibrogenic effects in various tissues, such as the liver
      and the biliary ducts. However, the role of SHH signaling in renal fibrogenesis
      remains to be elucidated. For this purpose, in the present study, we evaluated
      the hypothesis that activated SHH signaling promotes the acquisition of a
      myofibroblastic phenotype through the epithelial-mesenchymal transition (EMT),
      resulting in renal interstitial fibrosis (RIF). Kidney samples from rats
      subjected to unilateral or bilateral ureteral obstruction exhibited the enhanced
      expression of SHH-pathway proteins, mesenchymal markers and the decreased
      expression of epithelial markers. Overactive SHH signaling as well as tubular EMT
      and RIF in the obstructed kidneys were inhibited by recanalization of the ureter.
      In vitro, SHH signaling was activated during EMT induction and extracellular
      matrix (ECM) deposition was observed in transforming growth factor-beta1 (TGF
      beta1)-treated renal tubular epithelial cells [RTECs; NRK-52E cell line].
      Exogenous SHH activated SHH signaling and resulted in the upregulated expression
      of mesenchymal genes, the profibrogenic cytokine TGF-beta1, and the downregulated
      expression of epithelial markers. The blockade of SHH signaling with cyclopamine
      abolished SHH-mediated EMT as well as the acquisition of a myofibroblastic
      phenotype, and decreased TGF-beta1 expression and ECM production. Thus, taken
      together, these findings demonstrate that the activation of the SHH signaling
      pathway promotes the induction of EMT and renal tubulointerstitial fibrosis. The
      pharmacological inhibition of SHH signaling may potentially be of therapeutic
      value in the management of fibrotic kidney diseases.

PMID- 27035419
TI  - MAP30 inhibits autophagy through enhancing acetyltransferase p300 and induces
      apoptosis in acute myeloid leukemia cells.
AB  - Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) has been
      shown to exhibit potent antitumor activities against several solid tumors. In the
      present investigation we demonstrated that MAP30 significantly inhibited the
      proliferation of acute myeloid leukemia (AML) HL-60 and THP-1 cell lines and
      patient AML cells through autophagy inhibition and apoptosis induction.
      Intriguingly, MAP30-induced cell death and apoptosis were partially rescued in
      combination with an autophagy activator rapamycin, and aggravated in combination
      with an autophagy inhibitor bafilomycin A1 in HL-60 cells, suggesting that
      autophagy is a pro-survival signal and its inhibition contributes to the
      induction of apoptosis in MAP30-induced cell death. Further mechanism analysis
      demonstrated that MAP30 enhanced p300, and C646, a selective inhibitor of p300,
      markedly promoted autophagy and partially rescued the MAP30-induced cell death in
      HL-60 cells and patient AML cells. Collectively, our findings suggest that
      apoptosis and autophagy act cooperatively to elicit MAP30-induced cell death and
      MAP30 may be a potential antitumor drug candidate against AML. 

PMID- 27035420
TI  - Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene-7,8-diol
      9,10-epoxide-induced S-phase arrest of bronchial epithelial cells.
AB  - Nuclear respiratory factor 1 (NRF-1) has important roles in the regulation of
      several key metabolic genes required for cellular growth and respiration. A
      previous study by our group indicated that NRF-1 is involved in mitochondrial
      dysfunction induced by the environmental pollutant benzo[a]pyrene in the 16HBE
      human bronchial epithelial cell line. In the present study, it was observed that
      its genotoxic metabolite, anti-benzopyrene-7,8-diol-9,10-epoxide (BPDE),
      triggered cell cycle arrest in S-phase in 16HBE cells by activating ataxia
      telangiectasia (ATM)/checkpoint kinase (Chk)2 and ATM and Rad3 related (ATR)/Chk1
      signaling pathways. NRF-1 expression was suppressed by BPDE after treatment for 6
      h. Flow cytometric analysis revealed that NRF-1 overexpression attenuated cell
      cycle arrest in S-phase induced by BPDE. In line with this result, DNA-damage
      checkpoints were activated following NRF-1 overexpression, as demonstrated by
      increased phosphorylation of ATM, Chk2 and gammaH2AX, but not ATR and Chk1,
      according to western blot analysis. It was therefore indicated that NRF-1
      overexpression attenuated BPDE-induced S-phase arrest via the ATM/Chk2 signaling
      pathway. 

PMID- 27035421
TI  - Co-culture with podoplanin+ cells protects leukemic blast cells with leukemia
      associated antigens in the tumor microenvironment.
AB  - Podoplanin+ cells are indispensable in the tumor microenvironment. Increasing
      evidence suggests that podoplanin may support the growth and metastasis of solid
      tumors; however, to the best of our knowledge no studies have determined whether
      or not podoplanin serves a supportive role in acute myeloid leukemia (AML). The
      effects of co-culture with podoplanin+ cells on the cellular activities of the
      leukemic cells, such as apoptosis and cell proliferation, in addition to the
      expression of podoplanin in leukemic cells, were investigated. Due to the fact
      that genetic abnormalities are the primary cause of leukemogenesis, the
      overexpression of the fibromyalgia-like tyrosine kinase-3 gene in colony forming
      units was also examined following cell sorting. Podoplanin+ cells were found to
      play a protective role against apoptosis in leukemic cells and to promote cell
      proliferation. Tumor-associated antigens, including Wilms' tumor gene 1 and
      survivin, were increased when leukemic cells were co-cultured with podoplanin+
      cells. In combination, the present results also suggest that podoplanin+ cells
      can function as stromal cells for blast cell retention in the AML tumor
      microenvironment. 

PMID- 27035423
TI  - Protective effect of berberine on doxorubicin-induced acute hepatorenal toxicity
      in rats.
AB  - Doxorubicin (DOX), a potent broad-spectrum chemotherapeutic agent used for the
      treatment of several types of cancer, is largely limited due to its serious side
      effects on non-target organs. Thus, the present study aimed to investigate
      whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX-induced acute
      hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups:
      i) Control group, ii) DOX group, iii) DOX+Ber (5 mg kg) group; iv) DOX+Ber (10 mg
      kg), and v) DOX+Ber (20 mg kg) group. In the tests, body weight, organ index,
      general condition and mortality were observed. In addition, the serum levels of
      alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol
      (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal
      function. Hepatorenal toxicity was further assessed using hematoxylin and eosin
      stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or
      tissue homogenate were also assessed to determine the mechanisms of action.
      Results suggested that pretreatment with Ber ameliorated the DOX-induced liver
      and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the
      damage observed histologically, such as hemorrhage and focal necrosis of liver
      and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber
      also exerted certain antioxidative properties through reversing the changes in
      the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that
      Ber has protective effects against DOX-induced acute hepatorenal toxicity in
      rats. Combination of Ber with DOX is a novel strategy that has the potential for
      protecting against DOX-induced hepatorenal toxicity in clinical practice. 

PMID- 27035422
TI  - Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual
      Treatment of Acute and Neuropathic Pain.
AB  - Herein, the opioid pharmacophore H-Dmt-d-Arg-Aba-beta-Ala-NH2 (7) was linked to
      peptide ligands for the nociceptin receptor. Combination of 7 and NOP ligands
      (e.g., H-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) led to binding affinities in the low
      nanomolar domain. In vitro, the hybrids behaved as agonists at the opioid
      receptors and antagonists at the nociceptin receptor. Intravenous administration
      of hybrid 13a (H-Dmt-d-Arg-Aba-beta-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) to mice
      resulted in potent and long lasting antinociception in the tail-flick test,
      indicating that 13a was able to permeate the BBB. This was further supported by a
      cell-based BBB model. All hybrids alleviated allodynia and hyperalgesia in
      neuropathic pain models. Especially with respect to hyperalgesia, they showed to
      be more effective than the parent compounds. Hybrid 13a did not result in
      significant respiratory depression, in contrast to an equipotent analgesic dose
      of morphine. These hybrids hence represent a promising avenue toward analgesics
      for the dual treatment of acute and neuropathic pain.

PMID- 27035424
TI  - Effects of resveratrol and genistein on nuclear factor-kappaB, tumor necrosis
      factor-alpha and matrix metalloproteinase-9 in patients with chronic obstructive
      pulmonary disease.
AB  - Chronic airway inflammation and airway remodeling are the major
      pathophysiological characteristics of chronic obstructive pulmonary disease
      (COPD). Resveratrol and genistein have been previously demonstrated to have anti
      inflammatory and antioxidative properties. The present study aimed to measure the
      inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)
      alpha and matrix metalloproteinase (MMP)-9 concentration in patients with COPD.
      Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy
      subjects, then randomly divided into the following four treatment groups:
      Control, dexamethasone (0.5 umol/l), resveratrol (12.5 umol/l) and genistein (25
      umol/l) groups. After 1 h of treatment, 100 ul lymphocytes were collected for
      nuclear factor (NF)-kappaB immunocytochemical staining. After 48 h treatment, the
      supernatant of the lymphocytes was collected for analysis of TNF-alpha and MMP-9
      concentration levels. The percentage of lymphocytes with positive nuclear NF
      kappaB expression was analyzed by immunocytochemical staining. The concentration
      levels of TNF-alpha and MMP-9 were measured using radioimmunoassay and enzyme
      linked immunosorbent assay, respectively. The present study demonstrated that the
      percentage of NF-kappaB-positive cells, and the levels of TNF-alpha and MMP-9 in
      lymphocytes from patients with COPD patients were significantly higher compared
      with healthy subjects. Additionally, there were positive correlations between the
      percentage of NF-kappaB-positive cells, and the concentration levels of TNF-alpha
      and MMP-9 in patients with COPD. All three factors were significantly reduced in
      lymphocytes treated with resveratrol and genistein, and the inhibitory effects of
      resveratrol on NF-kappaB, TNF-alpha and MMP-9 were more potent than the effects
      of genistein. In conclusion, resveratrol and genistein may inhibit the NF-kappaB,
      TNF-alpha and MMP-9-associated pathways in patients with COPD. It is suggested
      that resveratrol and genistein may be potential drugs candidates for use in the
      treatment of COPD. 

PMID- 27035425
TI  - Prediction of key genes in ovarian cancer treated with decitabine based on
      network strategy.
AB  - The objective of the present study was to predict key genes in ovarian cancer
      before and after treatment with decitabine utilizing a network approach and to
      reveal the molecular mechanism. Pathogenic networks of ovarian cancer before and
      after treatment were identified based on known pathogenic genes (seed genes) and
      differentially expressed genes (DEGs) detected by Significance Analysis of
      Microarrays (SAM) method. A weight was assigned to each gene in the pathogenic
      network and then candidate genes were evaluated. Topological properties (degree,
      betweenness, closeness and stress) of candidate genes were analyzed to
      investigate more confident pathogenic genes. Pathway enrichment analysis for
      candidate and seed genes were conducted. Validation of candidate gene expression
      in ovarian cancer was performed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) assays. There were 73 nodes and 147 interactions in the
      pathogenic network before treatment, while 47 nodes and 66 interactions after
      treatment. A total of 32 candidate genes were identified in the before treatment
      group of ovarian cancer, of which 16 were rightly candidate genes after treatment
      and the others were silenced. We obtained 5 key genes (PIK3R2, CCNB1, IL2, IL1B
      and CDC6) for decitabine treatment that were validated by RT-PCR. In conclusion,
      we successfully identified 5 key genes (PIK3R2, CCNB1, IL2, IL1B and CDC6) and
      validated them, which provides insight into the molecular mechanisms of
      decitabine treatment and may be potential pathogenic biomarkers for the therapy
      of ovarian cancer. 

PMID- 27035426
TI  - Farnesyl pyrophosphate synthase inhibitor, ibandronate, improves endothelial
      function in spontaneously hypertensive rats.
AB  - Reactive oxygen species (ROS), originating predominantly from vascular smooth
      muscle cells (VSMCs), lead to vascular damage and endothelial dysfunction in rats
      with hypertension. The downstream signaling pathways of farnesyl pyrophosphate
      (FPP) synthase, Ras-related C3 botulinum toxin substrate 1 (Rac1) and
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mediate the
      generation of ROS. The present study investigated the effect of the FPP synthase
      inhibitor, ibandronate, on ROS production, the possible beneficial effect on
      endothelial dysfunction and the underlying mechanisms in spontaneously
      hypertensive rats (SHRs). The SHRs were treated with ibandronate for 30 days.
      Endothelium-dependent and independent vasorelaxation were measured in isolated
      aortic rings. Additionally, VSMCs from the SHRs and Wistar-Kyoto (WKY) rats were
      cultured. The production of ROS and activation of NADPH oxidase were determined
      using fluorescence and chemiluminescence, respectively, in vivo and in vitro.
      Angiotensin II (Ang II) increased ROS production in the cultured VSMCs from the
      WKY rats and SHRs, in a concentration-dependent manner. The Ang II-induced
      responses were more marked in the SHR VSMCs, compare with those in the WKY VSMCs,
      however, the response decreased significantly following ibandronate pretreatment.
      Treatment with ibandronate significantly decreased the production of ROS,
      translocation of NADPH oxidase subunit p47phox, and activities of NADPH oxidase
      and Rac1 in the aorta and VSMCs, and improved the impaired endothelium-dependent
      vasodilation in the SHRs. Adding geranylgeraniol, but not farnesol or mevalonate,
      reversed the inhibitory effects of ibandronate. In addition, inhibiting
      geranylgeranyl-transferase mimicked the effect of ibandronate on the excess
      oxidative response. Ibandronate exerted cellular antioxidant effects through the
      Rac1/NADPH oxidase pathway. These effects may have contributed to the
      vasoprotective effects on the impaired endothelium in SHRs. 

PMID- 27035427
TI  - miR-19a-3p targets PMEPA1 and induces prostate cancer cell proliferation,
      migration and invasion.
AB  - Prostate cancer (PCa) is one of the most common malignant tumors in men. Studies
      have observed that microRNA (miR)-19a-3p expression levels are downregulated in
      several types of cancer, and yet the biological function and its underlying
      mechanisms in the pathogenesis of PCa remain unclear. In the current study, the
      expression pattern of miR-19a-3p in PCa tissues and cell lines was detected by
      reverse transcription-quantitative polymerase chain reaction. The proliferative,
      migratory and invasive capacity of PCa cells were determined using EdU and
      Transwell assays following transfection with miR-19a-3p mimics. Additionally, the
      current study investigated the biological impact and regulation of prostate
      transmembrane protein androgen induced 1 (PMEPA1) in PCa cells by transfection
      with PMEPA1 small interfering (si)RNA. It was observed that miR-19a-3p was
      upregulated in PCa tissue samples and cell lines in vitro. Functional analysis
      also confirmed that miR-19a-3p overexpression promoted the proliferation,
      migration and invasion of PCa cells. Furthermore, PMEPA1 was identified as a
      direct target of miR-19a-3p, and siRNA knockdown of PMEPA1 resulted in increased
      proliferation, migration and invasion of PCa cells, which partially accounts for
      the effect of miR-19a-3p in tumor metastasis. In conclusion, the findings of the
      present study suggest that the upregulation of miR-19a-3p expression levels
      contributes to tumor progression and that one of its underlying mechanisms
      involves inhibition of PMEPA1 expression. 

PMID- 27035428
TI  - Interaction between angiotensin II and relaxin 2 in the progress of growth and
      spread of prostate cancer cells.
AB  - Deregulation of locally secreted hormones, such as angiotensin II (Ang II) and
      relaxin 2 (RLN2), has been linked to a higher risk of select cancers or a poor
      prognosis in patients. In this study, for the first time a common effect of Ang
      II and RLN2 in relation to various aspects of prostate cancer development and
      metastasis are presented. Four independent colorimetric assays were used to
      analyze cell viability and proliferation. The changes of cell adhesion to
      extracellular matrix proteins and invasion/aggressiveness ability of prostate
      cancer cells (LNCaP, PC3) before and after peptides treatment, were also
      investigated. The findings suggest that the both investigated systems, have an
      impact on cell growth/division or spread, to some degree via overlapping signal
      transduction pathways. Intermediate or sometimes poorer results were achieved by
      using a combination of both hormones than when each was used individually. It
      seems that Ang II and RLN2 can play a significant role in increasing the
      aggressiveness of prostate tumors by up-regulating BIRC5 expression and MMP-2 and
      MMP-9 secretion. In addition, we speculate that Ang II and RLN2 are involved in
      the transition from the androgen-dependent to the androgen-independent phenotype
      via modulation of the expression of androgen receptors. 

PMID- 27035429
TI  - miR-491-5p suppresses cell growth and invasion by targeting Notch3 in
      nasopharyngeal carcinoma.
AB  - MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal
      carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent
      in Southern China. miR-491-5p has been implicated in multiple types of cancer;
      however, its biological role and underlying mechanism in NPC have not been fully
      explored. In the present study, we found that miR-491-5p was downregulated in NPC
      tissues and cell lines compared with the corresponding normal counterparts.
      Overexpression of miR-491-5p significantly inhibited cell proliferation,
      migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA
      target prediction algorithms and reporter assays, we showed that miR-491-5p
      suppressed Notch3 expression both at the mRNA and protein level through directly
      targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of
      Notch3 significantly reversed the tumor-suppressive effects of miR-491-5p. Taken
      together, the present study reveals a mechanistic link between miR-491-5p and
      Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a
      therapeutic target for NPC. 

PMID- 27035430
TI  - Construction of SET overexpression vector and its effects on the proliferation
      and apoptosis of 293T cells.
AB  - The expression of SET nuclear proto-oncogene (SET) is commonly associated with
      cell proliferation and tumorigenesis. In the present study, a eukaryotic SET
      expression plasmid (pEGFP-N1-SET) was constructed and transiently transfected
      into 293T human embryonic kidney cells. Transfection led to expression of the SET
      oncoprotein at high levels, as indicated by polymerase chain reaction and western
      blot analysis. In addition, the relative mRNA and protein expression of protein
      phosphatase 2A in pEGFP-N1-SET-transfected 293T cells was downregulated compared
      with that in empty vector-transfected cells. Furthermore, overexpression of SET
      increased the percentage of 293T cells in S and G2/M phases compared with the
      control transfectants. An increase in B-cell lymphoma 2 (Bcl-2) and a decrease in
      Bcl-2-associated X (Bax) protein expression was observed in the pEGFP-N1-SET
      transfected cells compared with that in the controls, and their susceptibility to
      As4S4-induced apoptosis was decreased. The protein SET is involved in a number of
      cellular processes, including DNA replication, chromatin remodeling, gene
      transcription, differentiation, migration and cell cycle regulation. SET is
      overexpressed in several neoplasms, particularly in acute myeloid leukemia. The
      findings of the present study suggested that the SET gene may contribute to
      tumorigenesis and may be a potential novel effective therapeutic target for
      leukemia and other cancer types. 

PMID- 27035431
TI  - Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle
      arrest and apoptosis.
AB  - Primary gallbladder cancer (GBC) is the most common malignancy of the digestive
      system. Due to its resistance to standard chemotherapy, no effective treatments
      are available at present. Artemisinin, a plant-derived anti-malarial drug, has
      recently been shown to have anti-proliferative effects on a range of human cancer
      cell types. However, the efficacy of artemisinin against gallbladder cancer has
      not been reported. The present study investigated the effects of artemisinin on
      the proliferation, cell cycle and apoptosis of gallbladder cancer cell lines. A
      cell viability assay and an in vivo xenograft study demonstrated that artemisinin
      significantly inhibited the growth of gallbladder cancer. Western blot analysis
      indicated that artemisinin induced the expression of p16, while down-regulating
      phosphorylated extracellular signal-regulated kinase (ERK)1/2, CDK4 and cyclin D1
      expression, leading to inhibition of the ERK1/2 pathway. Furthermore, flow
      cytometry and western blot analysis showed that artemisinin caused G1-phase
      arrest of the cell cycle, promoted the generation of reactive oxygen species
      (ROS), led to a collapse of the mitochondrial membrane potential and to triggered
      cytochrome c release from the mitochondria into the cytoplasm, which finally
      activated caspase-3-mediated apoptosis. In conclusion, the present study
      demonstrated that artemisinin inhibits the proliferation of gallbladder cancer
      cells in vitro as well as in vivo and induces apoptosis via induction of ROS and
      cell cycle arrest. These results suggested that artemisinin may be suitable for
      the treatment of gallbladder cancer. 

PMID- 27035432
TI  - Downregulation of beta-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling
      through HuR.
AB  - beta-adrenergic receptors (beta-ARs) play an important role in cardiac
      remodeling, which is the key pathological process in various heart diseases and
      leads to heart failure. However, the regulation of beta-AR expression in
      remodeling hearts is still unclear. This study aims to clarify the possible
      mechanisms underlying the regulation of beta1- and beta2-AR expression in cardiac
      remodeling. The rat model of cardiac remodeling was established by subcutaneous
      injection of isoproterenol(ISO) at the dose of 0.25 mg.kg(-1).d(-1) for 7 days.
      We found that the expression of beta1- and beta2-ARs decreased in the remodeling
      heart. The mechanisms may include the inhibition of DNA transcription and the
      increase of mRNA degradation. cAMP-response element binding protein(CREB) is a
      well-known transcription factor of beta-AR. However, the expression and
      activation of CREB was not changed in the remodeling heart. Further, human
      Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region
      of the beta-AR mRNA and promotes RNA degradation, was increased in the remodeling
      model. And in vitro, HuR deficiency reversed the reduction of beta-AR mRNA
      induced by ISO. Therefore, the present findings indicate that HuR, but not CREB,
      is responsible for the reduction of beta-AR expression in ISO induced cardiac
      remodeling.

PMID- 27035433
TI  - Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression
      Data.
AB  - BACKGROUND: Identifying cancer subtypes is an important component of the
      personalised medicine framework. An increasing number of computational methods
      have been developed to identify cancer subtypes. However, existing methods rarely
      use information from gene regulatory networks to facilitate the subtype
      identification. It is widely accepted that gene regulatory networks play crucial
      roles in understanding the mechanisms of diseases. Different cancer subtypes are
      likely caused by different regulatory mechanisms. Therefore, there are great
      opportunities for developing methods that can utilise network information in
      identifying cancer subtypes. RESULTS: In this paper, we propose a method,
      weighted similarity network fusion (WSNF), to utilise the information in the
      complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We
      firstly build the regulatory network where the nodes represent the features, i.e.
      the microRNAs (miRNAs), transcription factors (TFs) and messenger RNAs (mRNAs)
      and the edges indicate the interactions between the features. The interactions
      are retrieved from various interatomic databases. We then use the network
      information and the expression data of the miRNAs, TFs and mRNAs to calculate the
      weight of the features, representing the level of importance of the features. The
      feature weight is then integrated into a network fusion approach to cluster the
      samples (patients) and thus to identify cancer subtypes. We applied our method to
      the TCGA breast invasive carcinoma (BRCA) and glioblastoma multiforme (GBM)
      datasets. The experimental results show that WSNF performs better than the other
      commonly used computational methods, and the information from miRNA-TF-mRNA
      regulatory network contributes to the performance improvement. The WSNF method
      successfully identified five breast cancer subtypes and three GBM subtypes which
      show significantly different survival patterns. We observed that the expression
      patterns of the features in some miRNA-TF-mRNA sub-networks vary across different
      identified subtypes. In addition, pathway enrichment analyses show that the top
      pathways involving the most differentially expressed genes in each of the
      identified subtypes are different. The results would provide valuable information
      for understanding the mechanisms characterising different cancer subtypes and
      assist the design of treatment therapies. All datasets and the R scripts to
      reproduce the results are available online at the website:
      http://nugget.unisa.edu.au/Thuc/cancersubtypes/.

PMID- 27035434
TI  - Population Structure in Naegleria fowleri as Revealed by Microsatellite Markers.
AB  - Naegleria sp. is a free living amoeba belonging to the Heterolobosea class. Over
      40 species of Naegleria were identified and recovered worldwide in different
      habitats such as swimming pools, freshwater lakes, soil or dust. Among them, N.
      fowleri, is a human pathogen responsible for primary amoeboic meningoencephalitis
      (PAM). Around 300 cases were reported in 40 years worldwide but PAM is a fatal
      disease of the central nervous system with only 5% survival of infected patients.
      Since both pathogenic and non pathogenic species were encountered in the
      environment, detection and dispersal mode are crucial points in the fight against
      this pathogenic agent. Previous studies on identification and genotyping of N.
      fowleri strains were focused on RAPD analysis and on ITS sequencing and
      identified 5 variants: euro-american, south pacific, widespread, cattenom and
      chooz. Microsatellites are powerful markers in population genetics with broad
      spectrum of applications (such as paternity test, fingerprinting, genetic mapping
      or genetic structure analysis). They are characterized by a high degree of length
      polymorphism. The aim of this study was to genotype N. fowleri strains using
      microsatellites markers in order to track this population and to better
      understand its evolution. Six microsatellite loci and 47 strains from different
      geographical origins were used for this analysis. The microsatellite markers
      revealed a level of discrimination higher than any other marker used until now,
      enabling the identification of seven genetic groups, included in the five main
      genetic groups based on the previous RAPD and ITS analyses. This analysis also
      allowed us to go further in identifying private alleles highlighting intra-group
      variability. A better identification of the N. fowleri isolates could be done
      with this type of analysis and could allow a better tracking of the clinical and
      environmental N. fowleri strains. 

PMID- 27035435
TI  - Correlated Observations, the Law of Small Numbers and Bank Runs.
AB  - Empirical descriptions and studies suggest that generally depositors observe a
      sample of previous decisions before deciding if to keep their funds deposited or
      to withdraw them. These observed decisions may exhibit different degrees of
      correlation across depositors. In our model depositors decide sequentially and
      are assumed to follow the law of small numbers in the sense that they believe
      that a bank run is underway if the number of observed withdrawals in their sample
      is large. Theoretically, with highly correlated samples and infinite depositors
      runs occur with certainty, while with random samples it needs not be the case, as
      for many parameter settings the likelihood of bank runs is zero. We investigate
      the intermediate cases and find that i) decreasing the correlation and ii)
      increasing the sample size reduces the likelihood of bank runs, ceteris paribus.
      Interestingly, the multiplicity of equilibria, a feature of the canonical Diamond
      Dybvig model that we use also, disappears almost completely in our setup. Our
      results have relevant policy implications. 

PMID- 27035436
TI  - Markov Model Predicts Changes in STH Prevalence during Control Activities Even
      with a Reduced Amount of Baseline Information.
AB  - BACKGROUND: Estimating the reduction in levels of infection during implementation
      of soil-transmitted helminth (STH) control programmes is important to measure
      their performance and to plan interventions. Markov modelling techniques have
      been used with some success to predict changes in STH prevalence following
      treatment in Viet Nam. The model is stationary and to date, the prediction has
      been obtained by calculating the transition probabilities between the different
      classes of intensity following the first year of drug distribution and assuming
      that these remain constant in subsequent years. However, to run this model
      longitudinal parasitological data (including intensity of infection) are required
      for two consecutive years from at least 200 individuals. Since this amount of
      data is not often available from STH control programmes, the possible application
      of the model in control programme is limited. The present study aimed to address
      this issue by adapting the existing Markov model to allow its application when a
      more limited amount of data is available and to test the predictive capacities of
      these simplified models. METHOD: We analysed data from field studies conducted
      with different combination of three parameters: (i) the frequency of drug
      administration; (ii) the drug distributed; and (iii) the target treatment
      population (entire population or school-aged children only). This analysis
      allowed us to define 10 sets of standard transition probabilities to be used to
      predict prevalence changes when only baseline data are available (simplified
      model 1). We also formulated three equations (one for each STH parasite) to
      calculate the predicted prevalence of the different classes of intensity from the
      total prevalence. These equations allowed us to design a simplified model (SM2)
      to obtain predictions when the classes of intensity at baseline were not known.
      To evaluate the performance of the simplified models, we collected data from the
      scientific literature on changes in STH prevalence during the implementation of
      26 control programmes in 16 countries. Using the baseline data observed, we
      applied the simplified models and predicted the onward prevalence of STH
      infection at each time-point for which programme data were available. We then
      compared the output from the model with the observed data from the programme.
      RESULTS: The comparison between the model-predicted prevalence and the observed
      values demonstrated a good accuracy of the predictions. In 77% of cases the
      original model predicted a prevalence within five absolute percentage points from
      the observed figure, for the simplified model one in 69% of cases and for the
      simplified model two in 60% of cases. We consider that the STH Markov model
      described here could be an important tool for programme managers to monitor the
      progress of their control programmes and to select the appropriate intervention.
      We also developed, and made freely available online, a software tool to enable
      the use of the STH Markov model by personnel with limited knowledge of
      mathematical models.

PMID- 27035437
TI  - Measuring Psychological Capital: Construction and Validation of the Compound
      PsyCap Scale (CPC-12).
AB  - With the Psychological Capital Questionnaire (PCQ) being the standard measure to
      assess psychological capital (PsyCap) in the context of organizations, this paper
      aims to broaden this domain-specific approach by introducing a measure with
      universal claim. Two studies were conducted to create and validate a German self
      report scale (CPC-12) measuring PsyCap. We performed confirmatory factor analyses
      and correlations with other positive psychological constructs on the data of two
      German samples (N1 = 321; N2 = 202). The twelve-item CPC-12 exhibits the
      anticipated factorial structure with a very good model fit and associations to
      other constructs concur with previous findings with other measures of PsyCap. 

PMID- 27035438
TI  - ["I was Delegated by the Federal State of Hesse to Assist in a Developmental
      Program for the Newly-Formed German States". A Retrospection on the Occasion of
      Elmar Brahlers 70th Birthday].

PMID- 27035439
TI  - [Third Wave Therapies of Cognitive Behavioral Therapy for Obsessive Compulsive
      Disorder: A Reasonable Add-on Therapy for CBT? State of the Art].
AB  - Cognitive behavioral therapy (CBT) with exposure is the state of the art and most
      efficient treatment for obsessive compulsive disorder and recommended as
      treatment of 1st choice according to guidelines. Therapies of the third wave,
      such as mindfulness based approaches (ACT, MBCT), metacognitive therapy, CBASP or
      schema therapy, have become more popular over past few years. A small number of
      studies that investigated some of these therapies show promising results.
      However, due to the small number of available studies, small sample sizes and
      methodologic limitations (only a few available RCTs) the evidence of these
      therapies is insufficient. Above all no study compared these alternative
      therapies with the well-proven CBT and exposure. Therefore, therapies of the
      third wave should only be used as add-on therapies to CBT and exposure if
      individually needed in the treatment of OCD. Future research is absolutely
      needed. 

PMID- 27035440
TI  - [Stigmatizing Attitudes towards Cancer Patients--Results of a Representative
      Population Survey].
AB  - OBJECTIVE: To investigate stigmatizing attitudes towards cancer patients in the
      general population and to examine their association with socio-structural
      characteristics and perceived causes of disease. METHODS: We recruited a
      representative sample from the German general population (n=2420; mean age: 52
      years; 54% women). Stigmatizing attitudes were assessed with a 9-item scale.
      Predictors of stigmatizing attitudes were identified using a regression analysis.
      RESULTS: Agreement with stigmatization items ranged from 3.6% (item: work
      together with a cancer patient) to 18.9% (item: use the same dishes as a cancer
      patient). Perceived causes of disease with a high levels of personal
      responsibility showed only weak correlations with stigmatizing attitudes (all
      r<0.31) and were partially statistical significant (e. g. food intake) or not
      significant (e. g. alcohol). The strongest predictors of stigmatizing attitudes
      were lack of cancer-related experiences (Beta=-0,26), age <60 years (Beta=0,1)
      and the assumption that one cannot protect oneself from cancer (Beta=0,11) (all
      p<0.001). Further predictors were male gender and living in rural area (p<0.01).
      CONCLUSION: The results demonstrate a need for further research and the
      development of valid methodological instruments to assess stigmatization towards
      cancer patients.

PMID- 27035441
TI  - [The Quality of the Family Physician-Patient Relationship. Patient-Related
      Predictors in a Sample Representative for the German Population].
AB  - BACKGROUND: Patient-centeredness and a strong working alliance are core elements
      of family medicine. Surveys in Germany showed that most people are satisfied with
      the quality of the family physician-patient relationship. However, factors that
      are responsible for the quality of the family physician-patient relationship
      remain unclear. This study aimed at identifying patient-related predictors of the
      quality of this relationship. MATERIALS AND METHODS: Participants of a cross
      sectional survey representative for the general German population were assessed
      using standardized questionnaires. The perceived quality of the family physician
      patient relationship was measured with the German version of the Patient-Doctor
      Relationship Questionnaire (PDRQ-9). Associations of demographic and clinical
      variables (comorbidity, somatic symptom burden, psychological distress) with the
      quality of the family physician-patient relationship were assessed by applying
      hierarchical linear regression. RESULTS: 2278 participants (91,9%) reported
      having a family physician. The mean total score of the PDRQ-9 was high (M=4,12,
      SD=0,70). The final regression model showed that higher age, being female, and
      most notably less somatic and less depressive symptoms predicted a higher quality
      of the family physician-patient relationship. Comorbidity lost significance when
      somatic symptom burden was added to the regression model. The final model
      explained 11% of the variance, indicating a small effect. CONCLUSIONS:
      Experiencing somatic and depressive symptoms emerged as most relevant patient
      related predictors of the quality of the family physician-patient relationship.

PMID- 27035442
TI  - [Prevalence of Disturbed Eating Behavior in Children and Adolescents with Type 1
      Diabetes: Assessment and Comparison to Healthy Peers--Results of a Multicenter
      Questionnaire-based Study].
AB  - INTRODUCTION: Published data on prevalence of disturbed eating behavior in youth
      with type 1 diabetes are heterogeneous. This study assesses the prevalence rate
      of disturbed eating behavior in a representative German sample of children and
      adolescents with type 1 diabetes. The prevalence rate is compared to the one
      published for a national sample of healthy peers. Furthermore prospects as well
      as limits of a generic screening tool used to identify disturbed eating behavior
      are compared to those of a diabetes specific screening tool. MATERIAL AND
      METHODS: A total of 246 children and adolescents (age: 11-19 years) with type 1
      diabetes, from 6 pediatric diabetes centers in Germany, completed the generic
      SCOFF questionnaire and the diabetes specific Diabetes Eating Problem Survey
      Revised (DEPS-R) to assess their eating behavior. Prevalence data were compared
      to representative data from a nationwide survey in Germany (KiGGS-study).
      RESULTS: A total of 16.3% of the children and adolescents with type 1 diabetes
      scored above the SCOFF cut-off (>= 2) (24.2% of the girls and 8.9% of the boys).
      The percentages in the healthy controls were 28.9% for girls and 15.2% for boys.
      Compared to this the prevalence of disturbed eating behavior was lower in the
      diabetes group (p=0.017 and p<0.001). According to the diabetes specific DEPS-R
      11.2% of the boys and 13.2% of the girls with type 1 diabetes practiced insulin
      purging. The association between SCOFF-scores and the items referring to insulin
      purging in DEPS-R, was stronger for girls than for boys (r=0.437 vs. r=0.144).
      Among the young people with type 1 diabetes DEPS-R-scores showed stronger
      associations to the quality of metabolic control (HbA1c) than the SCOFF (boys:
      r=0.357 vs. r=0.217 and girls: r=0.368 vs. r=0.131). DISCUSSION: Children and
      adolescents with type 1 diabetes are not more frequently affected by disturbed
      eating behavior than their healthy peers. Particularly boys with type 1 diabetes
      practicing insulin-purging, are not reliably detected by a generic screening
      tool. CONCLUSION: As part of long-term care a diabetes specific screening tool
      should be used to identify adolescents with type 1 diabetes and disturbed eating
      behavior more reliably.

PMID- 27035443
TI  - [Development and Evaluation of a Teacher Training for the Early Recognition of
      Depressive Symptoms in Students].
AB  - BACKGROUND AND STUDY OBJECTIVES: Although teachers play an important role
      regarding early recognition of psychological problems in students, they have been
      largely neglected in research as a target group for interventions. In this study,
      a training for teachers was developed that aimed at improving knowledge and self
      efficacy/subjective competencies with regard to the early recognition of mental
      distress in secondary school students with a specific focus on depressive
      symptoms (by means of providing information, interviewing techniques, and
      important contact persons). METHODS: A training module comprising 4 h directed at
      teachers in secondary schools was developed and tested in 6 schools in a pre-post
      evaluation design. Participating teachers rated the training as well as their
      knowledge and self-efficacy/subjective competencies at 3 time points (before
      training (T1); after training (T2); 6-months-follow-up (T3)). RESULTS:
      Questionnaire data from N=44 teachers were available for all 3 data points
      (baseline sample: N=100). There was a slight but nonsignificant post-training
      increase in knowledge regarding depressive symptoms (partial Eta(2)=0,047). A
      significant benefit was found for most self-efficacy items (partial Eta(2)=0,14
      0,67). Participants reported gains in subjective competencies with regard to
      initiating a dialogue with a distressed student and approaching his/her parents.
      Training contents and realization were rated positively immediately after the
      training as well as at follow up. DISCUSSION: The evaluation of the teacher
      training for early recognition of mental distress in students showed promising
      preliminary results that should be substantiated in a randomized controlled
      design.

PMID- 27035444
TI  - [The Munich Attachment and Effectiveness Study: Study Design and a Case Example].
AB  - OBJECTIVES: The "Munich Attachment and Effectiveness Study" is a prospective
      psychotherapy study examining process and outcome of psychoanalytic
      psychotherapies. The study design and results are exemplified in a single case.
      METHODS: At 6 points in time audio-taped and transcribed therapy sessions are
      evaluated using process instruments (e. g. Psychotherapy Process Q-Set PQS) and
      interviews (e. g. Operationalized Psychodynamic Diagnostics OPD, Heidelberg
      Structural Change Scale HSCS, Adult Attachment Interview AAI). RESULTS: In the
      single case, findings from the psychotherapeutic process (e. g. "therapist is
      empathic" according to PQS) complement the achieved changes. 5 HSCS problem foci
      reached level of "restructuring", on the Reflective Functioning Scale a marked
      change of RF took place and the attachment classification changed over time.
      CONCLUSIONS: The instruments employed in this study corresponded well in
      assessing change processes in spite of differing theoretical background.

PMID- 27035445
TI  - [Psychometric Evaluation of the German Version of the Short Questionnaire for
      Family Members-Affected by Addiction SQFM-AA (Gambling)].
AB  - INTRODUCTION: Affected others of disordered gamblers are often heavily impacted
      because of the illness. Up till now, there is no standardized German instrument
      to assess this impact. Internationally, the Short Questionnaire for Family
      Members-affected by addiction (SQFM-AA) is often used which is based on the
      Stress-Strain-Coping-Support-Modell. That is why we translated this questionnaire
      into the German Kurzfragebogen fur suchtbelastete Familienmitglieder SQFM-AA
      (Version Glucksspiel) to be able to assess the impact on affected others and to
      compare our results internationally. METHODS: The SQFM-AA was translated and
      retranslated and tested in an online convenience sample of affected others.
      Essential psychometric properties, discriminatory power, and internal consistency
      were calculated. Factor structure was analysed using an exploratory factor
      analysis (principal axis analysis, varimax rotation). RESULTS: Data collected
      from 122 affected others (87% female; 67% partners; 61% joint household) were
      analysed. Discriminatory power ranges between 0.30-0.94, Cronbach's alpha between
      0.61-0.95. Factor analysis shows that 69% of variance can be explained in a
      solution with 9 factors. DISCUSSION: Due to the methods used when translating and
      back-translating the SQFM-AA, it can be assumed that both versions are
      comparable. Internal consistency of all scales is in an acceptable to good range.
      In our sample, the postulated 11 sub-scales cannot be reproduced. The 9 factors
      found here can be derived based on theoretical preliminary considerations. 4 of
      the scales are reflected well in the analysis, 3 more factors show a relevant
      load on other scales. Furthermore, one item each does not load on the proposed
      factor for the 2 remaining scales. All in all, the factors can be interpreted
      well regarding their content. A modification of the questionnaire would improve
      some of the statistical values, but the international comparability would no
      longer be possible. CONCLUSION: With the adaptation presented here, impact on
      affected others of disordered gamblers can be assessed and relevant areas for
      therapy and counselling can be identified.

PMID- 27035446
TI  - GENDER IN LOW- AND MIDDLE-INCOME COUNTRIES: INTRODUCTION
AB  - How do girls and boys in low- and middle-income countries (LMIC) in the majority
      world vary with respect to central indicators of child growth and mortality,
      parental caregiving, discipline and violence, and child labor? How do key
      indicators of national gender equity and economic development relate to gender
      similarities and differences in each of these substantive areas of child
      development? This monograph of the SRCD is concerned with central topics of child
      gender, gendered parenting, gendered environments, and gendered behaviors and
      socializing practices in the underresearched and underserved world of LMIC. To
      examine protective and risk factors related to child gender in LMIC around the
      world, we used data from more than 2 million individuals in 400,000 families in
      41 LMIC collected in the Multiple Indicator Cluster Survey, a household survey
      that includes nationally representative samples of participating countries. In
      the first chapter of this monograph, we describe the conceptual "gender
      similarities" and "bioecological" frameworks that helped guide the monograph. In
      the second chapter, we detail the general methodology adhered to in the
      substantive chapters. Then, in topical chapters, we describe the situations of
      girls and boys with successive foci on child growth and mortality, parental
      caregiving, family discipline and violence, and child labor. We conclude with a
      general discussion of findings from the substantive chapters in the context of
      gender and bioecological theories. Across 41 LMIC and four substantive areas of
      child development, few major gender differences emerged. Our data support a
      gender similarities view and suggest that general emphases on early child gender
      differences may be overstated at least for the developing world of LMIC.

PMID- 27035454
TI  - CONTEXT AND THE ADVANCEMENT OF A GLOBAL SCIENCE OF HUMAN DEVELOPMENT: A
      COMMENTARY.
AB  - United Nations agencies mandated to address the needs of children around the
      developing (Majority) world, routinely create large global data sets mostly for
      purposes of surveillance and strategic planning of development aid. UNICEF's
      Multiple Indicator Cluster Surveys (MICS) have produced one of the largest
      sources of internationally comparable data on women and children. This monograph
      creatively and elegantly harnesses MICS data on 41 low- and middle-income
      countries to shed light on risk and protective factors associated with growing up
      a boy or girl in the developing world. In this commentary, I assess the
      monograph's contribution to the progress that our field must make toward greater
      geo-ecological and cultural inclusiveness of its knowledge base. I do so in the
      context of scholarship that is increasingly and justifiably questioning the
      relevance of mainstream developmental science outside the Euro-American world. I
      conclude that notwithstanding the limitations inherent in the data set,
      Bornstein, Putnick, Lansford, Deater-Deckard, and Bradley have done our field a
      great service by moving us further on a trajectory toward a more global science. 

PMID- 27035455
TI  - Neurology in the Vietnam War.
AB  - Between December 1965 and December 1971, the United States maintained armed
      forces in Vietnam never less than 180,000 men and women in support of the war. At
      one time, this commitment exceeded half a million soldiers, sailors, and airmen
      from both the United States and its allies. Such forces required an extensive
      medical presence, including 19 neurologists. All but two of the neurologists had
      been drafted for a 2-year tour of duty after deferment for residency training.
      They were assigned to Vietnam for one of those 2 years in two Army Medical Units
      and one Air Force facility providing neurological care for American and allied
      forces, as well as many civilians. Their practice included exposure to unfamiliar
      disorders including cerebral malaria, Japanese B encephalitis, sleep deprivation
      seizures, and toxic encephalitis caused by injection or inhalation of C-4
      explosive. They and neurologists at facilities in the United States published
      studies on all of these entities both during and after the war. These
      publications spawned the Defense and Veterans Head Injury Study, which was
      conceived during the Korean War and continues today as the Defense and Veterans
      Head Injury Center. It initially focused on post-traumatic epilepsy and later on
      all effects of brain injury. The Agent Orange controversy arose after the war;
      during the war, it was not perceived as a threat by medical personnel. Although
      soldiers in previous wars had developed serious psychological impairments, post
      traumatic stress disorder was formally recognized in the servicemen returning
      from Vietnam. 

PMID- 27035456
TI  - Sources of Information as Determinants of Product and Process Innovation.
AB  - In this paper we use a panel of manufacturing firms in Spain to examine the
      extent to which they use internal and external sources of information (customers,
      suppliers, competitors, consultants and universities) to generate product and
      process innovation. Our results show that, although internal sources are
      influential, external sources of information are key to achieve innovation
      performance. These results are in line with the open innovation literature
      because they show that firms that are opening up their innovation process and
      that use different information sources have a greater capacity to generate
      innovations. We also find that the importance of external sources of information
      varies depending on the type of innovation (product or process) considered. To
      generate process innovation, firms mainly rely on suppliers while, to generate
      product innovation, the main contribution is from customers. The potential
      simultaneity between product and process innovation is also taken into
      consideration. We find that the generation of both types of innovation is not
      independent. 

PMID- 27035457
TI  - Staff Nurses' Perceptions and Experiences about Structural Empowerment: A
      Qualitative Phenomenological Study.
AB  - The aim of the study reported in this article was to investigate staff nurses'
      perceptions and experiences about structural empowerment and perceptions
      regarding the extent to which structural empowerment supports safe quality
      patient care. To address the complex needs of patients, staff nurse involvement
      in clinical and organizational decision-making processes within interdisciplinary
      care settings is crucial. A qualitative study was conducted using individual semi
      structured interviews of 11 staff nurses assigned to medical or surgical units in
      a 600-bed university hospital in Belgium. During the study period, the hospital
      was going through an organizational transformation process to move from a classic
      hierarchical and departmental organizational structure to one that was flat and
      interdisciplinary. Staff nurses reported experiencing structural empowerment and
      they were willing to be involved in decision-making processes primarily about
      patient care within the context of their practice unit. However, participants
      were not always fully aware of the challenges and the effect of empowerment on
      their daily practice, the quality of care and patient safety. Ongoing hospital
      change initiatives supported staff nurses' involvement in decision-making
      processes for certain matters but for some decisions, a classic hierarchical and
      departmental process still remained. Nurses perceived relatively high work
      demands and at times viewed empowerment as presenting additional. Staff nurses
      recognized the opportunities structural empowerment provided within their daily
      practice. Nurse managers and unit climate were seen as crucial for success while
      lack of time and perceived work demands were viewed as barriers to empowerment. 

PMID- 27035458
TI  - Plasmatic Ganglioside Profile and Age-Related Macular Degeneration: A Case
      Control Study.
AB  - PURPOSE: Gangliosides are glycosphingolipids that are particularly abundant in
      the nervous system, including the retina. However, their precise role in this
      tissue and its pathologies remain poorly understood. The objective of the present
      study was to characterize the ganglioside profile of human plasma and to
      determine whether it is affected in age-related macular degeneration (AMD).
      METHODS: Eighty-three subjects were included: control subjects (n = 25), atrophic
      AMD patients (n = 27) and exudative AMD patients (n = 31). For each subject,
      gangliosides were extracted from plasma and analyzed by liquid chromatography
      coupled to mass spectrometry. RESULTS: GM3 appeared to be by far the major
      ganglioside of human plasma, associated with GD3. No specific ganglioside class
      was detected in the plasma of AMD patients. Fourteen molecular species of GM3 and
      9 species of GD3, accounting for the variability of the ceramide moiety of the
      ganglioside molecule, were identified and characterized. Analyses revealed no
      significant differences in the proportion of these species between control,
      atrophic and exudative AMD patient groups. Total GM3 levels did not differ
      either. CONCLUSION: Although gangliosides are considered important for the
      retina's structure and function, it seems that circulating gangliosides are not
      associated with the retinal damage occurring during the course of AMD.

PMID- 27035459
TI  - Adductor Canal Block Versus Femoral Canal Block for Total Knee Arthroplasty: A
      Meta-Analysis: What Does the Evidence Suggest?

PMID- 27035460
TI  - Evaluation of a New Needle Guidance System for Ultrasound: Results of a
      Prospective, Randomized, Blinded Study.
AB  - BACKGROUND AND OBJECTIVES: Accurate needle control during ultrasound (US)-guided
      nerve blocks may be an elusive goal for the anesthesiologist. Despite
      modifications to increase echogenicity, needle visibility still requires precise
      alignment within the transducer beam. In this study, we evaluated a magnetically
      guided ultrasound (MGU) system that produces a real-time, graphic display of the
      needle position and trajectory that is independent of the US beam. METHODS: The
      MGU system was compared with echogenic needles and conventional ultrasound (CU)
      by anesthesiologists with and without prior experience performing US-guided nerve
      blocks. Participants were asked to perform tasks to quantify accuracy with
      respect to needle direction (directional accuracy) and needle tip position
      (positional accuracy). These evaluations were performed in a porcine tissue
      model. RESULTS: Regarding directional accuracy, inexperienced subjects were able
      to contact a target capsule with a single needle pass during both in-plane (IP)
      and out-of-plane (OOP) approaches using the magnetic guidance system. By
      contrast, using CU, subjects required redirection 3.8 +/- 2.4 (P = 0.02), and 4.5
      +/- 3.9 (P = 0.04) times, respectively, for IP and OOP approaches. Experienced
      subjects contacted the target capsule with a single pass for both IP and OOP
      approaches when using the magnetic guidance system. With CU, experienced subjects
      were able to contact the target with a single pass using an IP approach but
      required redirection 3.4 +/- 2.8 (P = 0.046) times during OOP approaches.
      Positional accuracy was also superior for both inexperienced (P = 0.04) and
      experienced (P = 0.02) users during an OOP approach. CONCLUSIONS: In a tissue
      model, the MGU system improved control of needle trajectory and needle tip
      position for both inexperienced and experienced subjects.

PMID- 27035461
TI  - Anatomic Basis for Brachial Plexus Block at the Costoclavicular Space: A Cadaver
      Anatomic Study.
AB  - BACKGROUND AND OBJECTIVES: The costoclavicular space (CCS), which is located deep
      and posterior to the midpoint of the clavicle, may be a better site for
      infraclavicular brachial plexus block than the traditional lateral paracoracoid
      site. However, currently, there is paucity of data on the anatomy of the brachial
      plexus at the CCS. We undertook this cadaver anatomic study to define the anatomy
      of the cords of the brachial plexus at the CCS and thereby establish the anatomic
      basis for ultrasound-guided infraclavicular brachial plexus block at this
      proximal site. METHODS: The anatomy and topography of the cords of the brachial
      plexus at the CCS was evaluated in 8 unembalmed (cryopreserved), thawed, fresh
      adult human cadavers using anatomic dissection, and transverse anatomic and
      histological sections, of the CCS. RESULTS: The cords of the brachial plexus were
      located lateral and parallel to the axillary artery at the CCS. The topography of
      the cords, relative to the axillary artery and to one another, in the transverse
      (axial) plane was also consistent at the CCS. The lateral cord was the most
      superficial of the 3 cords and it was always anterior to both the medial and
      posterior cords. The medial cord was directly posterior to the lateral cord but
      medial to the posterior cord. The posterior cord was the lateral most of the 3
      cords at the CCS and it was immediately lateral to the medial cord but
      posterolateral to the lateral cord. CONCLUSIONS: The cords of the brachial plexus
      are clustered together lateral to the axillary artery, and share a consistent
      relation relative to one another and to the axillary artery, at the CCS.

PMID- 27035462
TI  - Primary Failure of Thoracic Epidural Analgesia in Training Centers: The Invisible
      Elephant?
AB  - In teaching centers, primary failure of thoracic epidural analgesia can be due to
      multiple etiologies. In addition to the difficult anatomy of the thoracic spine,
      the conventional end point-loss-of-resistance-lacks specificity. Furthermore,
      insufficient training compounds the problem: learning curves are nonexistent,
      pedagogical requirements are often inadequate, supervisors may be inexperienced,
      and exposure during residency is decreasing. Any viable solution needs to be
      multifaceted. Learning curves should be explored to determine the minimal number
      of blocks required for proficiency. The problem of decreasing caseload can be
      tackled with epidural simulators to supplement in vivo learning. From a technical
      standpoint, fluoroscopy and ultrasonography could be used to navigate the complex
      anatomy of the thoracic spine. Finally, correct identification of the thoracic
      epidural space should be confirmed with objective, real-time modalities such as
      neurostimulation and waveform analysis.

PMID- 27035463
TI  - Acute Epidural Hematoma Formation in Cervical Spine After Interlaminar Epidural
      Steroid Injection Despite Discontinuation of Clopidogrel.
AB  - BACKGROUND: Perioperative management of patients on anticoagulant therapy prior
      to interventional pain procedures creates a challenge when balancing the risk of
      bleeding against thromboembolic events. CASE REPORT: We report a case of epidural
      hematoma formation in the cervical spine following interlaminar epidural steroid
      injection in an elderly woman with chronic neck and arm pain, who was on
      clopidogrel therapy. CONCLUSIONS: This is the first reported case of hematoma
      formation immediately following an epidural steroid injection possibly associated
      with clopidogrel, even though established guidelines on the timing of the
      discontinuation of clopidogrel prior to the procedure were exceeded. Severe pain
      appears to be the first symptom of hematoma formation, and therefore immediate
      diagnostic workup and evacuation of hematoma are essential in preventing
      neurological damage. It may be advisable to carry out a test specific for
      clopidogrel such as the P2Y12 to ensure that there is no residual action on
      platelet aggregation function, particularly in patients who may be slow
      metabolizers of clopidogrel. Caution is advised prior to administering analgesics
      with antiplatelet effects such as ketorolac.

PMID- 27035464
TI  - Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune
      System.
AB  - Sequence variation can affect the physiological state of the immune system. Major
      experimental efforts targeted at understanding the genetic control of the
      abundance of immune cell subpopulations. However, these studies are typically
      focused on a limited number of immune cell types, mainly due to the use of
      relatively low throughput cell-sorting technologies. Here we present an algorithm
      that can reveal the genetic basis of inter-individual variation in the abundance
      of immune cell types using only gene expression and genotyping measurements as
      input. Our algorithm predicts the abundance of immune cell subpopulations based
      on the RNA levels of informative marker genes within a complex tissue, and then
      provides the genetic control on these predicted immune traits as output. A key
      feature of the approach is the integration of predictions from various sets of
      marker genes and refinement of these sets to avoid spurious signals. Our
      evaluation of both synthetic and real biological data shows the significant
      benefits of the new approach. Our method, VoCAL, is implemented in the freely
      available R package ComICS. 

PMID- 27035465
TI  - Stimulating Effect of Terfenadine on Erythrocyte Cell Membrane Scrambling.
AB  - BACKGROUND/AIMS: The antihistaminic drug Terfenadine may trigger apoptosis of
      tumor cells, an effect unrelated to its effect on histamine receptors. Similar to
      apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal
      death of erythrocytes characterized by cell shrinkage and cell membrane
      scrambling with phosphatidylserine translocation to the erythrocyte surface.
      Signaling triggering eryptosis include increase of cytosolic Ca2+ activity
      ([Ca2+]i), oxidative stress, and ceramide. The present study explored, whether
      Terfenadine is capable to trigger eryptosis. METHODS: Flow cytometry was employed
      to estimate phosphatidylserine abundance at the erythrocyte surface from annexin
      V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence,
      abundance of reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein
      (DCF) diacetate dependent fluorescence, and ceramide abundance at the human
      erythrocyte surface utilizing specific antibodies. Hemolysis was quantified from
      haemoglobin concentration in the supernatant. RESULTS: A 48 hours exposure of
      human erythrocytes to Terfenadine (>= 5 uM) significantly increased the
      percentage of annexin-V-binding cells and triggered hemolysis without
      significantly modifying the average forward scatter. Terfenadine (7.5 uM)
      significantly increased Fluo3-fluorescence, but did not significantly modify DCF
      fluorescence or ceramide abundance. The effect of Terfenadine on annexin-V
      binding was significantly blunted but not abolished by removal of extracellular
      Ca2+. Exposure of human erythrocytes to Ca2+ ionophore ionomycin (1 uM, 15 min)
      triggered annexin-V-binding, an effect augmented by Terfenadine pretreatment (10
      uM, 48 hours). CONCLUSIONS: Terfenadine triggers phospholipid scrambling of the
      human erythrocyte cell membrane, an effect in part due to entry of extracellular
      Ca2+ and in part due to sensitizing human erythrocyte cell membrane scrambling to
      Ca2+.

PMID- 27035466
TI  - Current status of tissue monitoring in the management of shock.
AB  - PURPOSE OF REVIEW: Tissue monitoring is one of the main strategies at the bedside
      to guide resuscitation of shock. Advances in tissue monitoring technologies have
      established noninvasive optical methods and transcutaneous oximetry as modalities
      of considerable value in the critical care setting for tissue monitoring in
      shock. The purpose of this article is to highlight the latest developments into
      the clinical applications of near-infrared spectroscopy, direct visualization of
      sublingual microcirculation, and transcutaneous oxygen measurements (PtcO2).
      RECENT FINDINGS: Near-infrared spectroscopy has been successfully applied in
      patients with septic shock during vasopressor and blood transfusion therapy to
      identify patients at high risk for microcirculatory failure. A new generation
      incident dark field imaging-based handheld microscope has been introduced for
      quantification of microcirculatory alterations at bedside. Preliminary
      comparisons with previous versions have shown better quality and superiority of
      incident dark field in detecting more vessels. PtcO2 measurements have been
      applied mainly to detect a peripheral low-flow state in circulatory failure using
      the oxygen challenge test. Altered lung function might have an influence on
      PtcO2, and thus affect the oxygen challenge test. SUMMARY: The latest
      developments of noninvasive optical monitoring and transcutaneous oximetry
      technologies have helped early identification of septic patients at high risk for
      microcirculatory failure and could allow more targeted interventions in shock.

PMID- 27035468
TI  - The synthesis and aggregation-induced near-infrared emission of terrylenediimide
      tetraphenylethene dyads.
AB  - We design and synthesize terrylenediimide-tetraphenylethene dyads, which exhibit
      featured aggregation-induced near-infrared fluorescence with a maximum emission
      wavelength of up to 800 nm. 

PMID- 27035469
TI  - Diabetes Prevalence in Relation to Serum Concentrations of Polychlorinated
      Biphenyl (PCB) Congener Groups and Three Chlorinated Pesticides in a Native
      American Population.
AB  - BACKGROUND: Exposure to persistent organic pollutants (POPs) is known to increase
      risk of diabetes. OBJECTIVE: To determine which POPs are most associated with
      prevalence of diabetes in 601 Akwesasne Native Americans. METHODS: Multiple
      logistic regression analysis was used to assess associations between quartiles of
      concentrations of 101 polychlorinated biphenyl (PCBs) congeners, congener groups
      and three chlorinated pesticides [dichlorodiphenyldichloroethylene (DDE),
      hexachlorobenzene (HCB) and mirex] with diabetes. In Model 1, the relationship
      between quartiles of exposure and diabetes were adjusted only for sex, age, body
      mass index (BMI), and total serum lipids. Model 2 included additional adjustment
      for either total PCBs or total pesticides. RESULTS: Total serum PCB and pesticide
      concentrations were each significantly associated with prevalence of diabetes
      when adjusted only for covariates (Model 1), but neither showed a significant OR
      for highest to lowest quartiles after additional adjustment for the other (Model
      2). When applying Model 2 to PCB congener groups and individual pesticides, there
      were significant omnibus differences between the four quartiles (all ps < 0.042)
      for most groups, with the exception of penta- and hexachlorobiphenyls, DDE and
      mirex. However, when comparing highest to lowest quartiles only non- and mono
      ortho PCBs [OR = 4.55 (95% CI: 1.48, 13.95)], tri- and tetrachloro PCBs [OR =
      3.66 (95% CI: 1.37, -9.78)] and HCB [OR = 2.64 (95% CI: 1.05, 6.61)] showed
      significant associations with diabetes. Among the non- and mono-ortho congeners,
      highest to lowest quartile of dioxin TEQs was not significant [OR = 1.82 (95% CI:
      0.61, 5.40)] but the OR for the non-dioxin-like congeners was [OR = 5.01 (95% CI:
      1.76, 14.24)]. CONCLUSION: The associations with diabetes after adjustment for
      other POPs were strongest with the more volatile, non-dioxin-like, low
      chlorinated PCB congeners and HCB. Because low-chlorinated congeners are more
      volatile, these observations suggest that inhalation of vapor-phase PCBs is an
      important route of exposure. CITATION: Aminov Z, Haase R, Rej R, Schymura MJ,
      Santiago-Rivera A, Morse G, DeCaprio A, Carpenter DO, and the Akwesasne Task
      Force on the Environment. 2016. Diabetes prevalence in relation to serum
      concentrations of polychlorinated biphenyl (PCB) congener groups and three
      chlorinated pesticides in a Native American population. Environ Health Perspect
      124:1376-1383; http://dx.doi.org/10.1289/ehp.1509902.

PMID- 27035470
TI  - Fermentative utilization of coffee mucilage using Bacillus coagulans and
      investigation of down-stream processing of fermentation broth for optically pure
      l(+)-lactic acid production.
AB  - In this study, mucilage, a residue from coffee production, was investigated as
      substrate in fermentative l(+)-lactic acid production. Mucilage was provided as
      liquid suspension consisting glucose, galactose, fructose, xylose and sucrose as
      free sugars (up to 60gL(-1)), and used directly as medium in Bacillus coagulans
      batch fermentations carried out at 2 and 50L scales. Using mucilage and 5gL(-1)
      yeast extract as additional nitrogen source, more than 40gL(-1) lactic acid was
      obtained. Productivity and yield were 4-5gL(-1)h(-1) and 0.70-0.77g lactic acid
      per g of free sugars, respectively, irrespective the scale. Similar yield was
      found when no yeast extract was supplied, the productivity, however, was 1.5gL(
      1)h(-1). Down-stream processing of culture broth, including filtration,
      electrodialysis, ion exchange chromatography and distillation, resulted in a pure
      lactic acid formulation containing 930gL(-1)l(+)-lactic acid. Optical purity was
      99.8%. 

PMID- 27035471
TI  - Efficient and repeated production of succinic acid by turning sugarcane bagasse
      into sugar and support.
AB  - Here we reported an endeavor in making full use of sugarcane bagasse for
      biological production of succinic acid. Through NaOH pre-treatment and multi
      enzyme hydrolysis, a reducing sugar solution mainly composed of glucose and
      xylose was obtained from the sugarcane bagasse. By optimizing portions of
      cellulase, xylanase, beta-glucanase and pectinase in the multi-enzyme "cocktail",
      the hydrolysis percentage of the total cellulose in pre-treated sugarcane bagasse
      can be as high as 88.5%. A. succinogenes CCTCC M2012036 was used for converting
      reducing sugars into succinic acid in a 3-L bioreactor with a sugar-fed strategy
      to prevent cell growth limitation. Importantly, cells were found to be adaptive
      on the sugarcane bagasse residue, offering possibilities of repeated batch
      fermentation and replacement for MgCO3 with soluble NaHCO3 in pH modulation.
      Three cycles of fermentation without activity loss were realized with the average
      succinic acid yield and productivity to be 80.5% and 1.65g.L(-1).h(-1). 

PMID- 27035472
TI  - Influence of two-phase anaerobic digestion on fate of selected antibiotic
      resistance genes and class I integrons in municipal wastewater sludge.
AB  - The response of representative antibiotic resistance genes (ARGs) to lab-scale
      two-phase (acidogenic/methanogenic phase) anaerobic digestion processes under
      thermophilic and mesophilic conditions was explored. The associated microbial
      communities and bacterial pathogens were characterized by 16S rRNA gene
      sequencing. A two-phase thermophilic digestion reduced the presence of tetA,
      tetG, tetX, sul1, ermB, dfrA1, dfrA12 and intI1 exhibiting 0.1-0.72 log unit
      removal; in contrast, tetO, tetW, sul3, ermF and blaTEM even increased relative
      to the feed, and sul2 showed no significant decrease. The acidogenic phase of
      thermophilic digestion was primarily responsible for reducing the quantity of
      these genes, while the subsequent methanogenic phase caused a rebound in their
      quantity. In contrast, a two-phase mesophilic digestion process did not result in
      reducing the quantity of all ARGs and intI1 except for ermB and blaTEM. ARGs
      patterns were correlated with Proteobacteria and Actinobacteria during the two
      phase anaerobic digestion. 

PMID- 27035473
TI  - Evaluation of novel thermo-resistant Micractinium and Scenedesmus sp. for
      efficient biomass and lipid production under different temperature and nutrient
      regimes.
AB  - Despite the vast interest in microalgae as feedstock for biodiesel production,
      relatively few studies examined their response to diurnal temperature
      fluctuation. Here, we describe biomass and lipid productivities and fatty acid
      profiles of thermo-resistant Micractinium sp. and Scenedesmus sp. grown in batch
      cultures in a laboratory set-up that mimics a typically warm summer day in
      Central Anatolia with a 16-h light temperature of 30 degrees C and 8-h dark
      temperature of 16 degrees C (30 degrees C (day)/16 degrees C (night)). Both
      strains can survive a temperature range of 10-50 degrees C. We found the lipid
      productivities of Micractinium sp. and Scenedesmus sp. as 30/21mgL(-1)d(-1) and
      6/7mgL(-1)d(-1), respectively during the 30 degrees C (day)/16 degrees C (night)
      cycle. Saturated fatty acid content increased with increasing temperature.
      Additionally, we cultured Micractinium sp. under Nitrogen (N) and Phosphorus (P)
      limiting conditions. Highest lipid productivity of 85.4+/-2mgL(-1)d(-1) was
      obtained under P-depletion during exponential growth phase. Oleic acid amount
      also increased eight fold during P-deplete. 

PMID- 27035474
TI  - Improving microalgal growth with reduced diameters of aeration bubbles and
      enhanced mass transfer of solution in an oscillating flow field.
AB  - A novel oscillating gas aerator combined with an oscillating baffle was proposed
      to generate smaller aeration bubbles and enhance solution mass transfer, which
      can improve microalgal growth in a raceway pond. A high-speed photography system
      (HSP) was used to measure bubble diameter and generation time, and online precise
      dissolved oxygen probes and pH probes were used to measure mass-transfer
      coefficient and mixing time. Bubble diameter and generation time decreased with
      decreased aeration gas rate, decreased orifice diameter, and increased water
      velocity in the oscillating gas aerator. The optimized oscillating gas aerator
      decreased bubble diameter and generation time by 25% and 58%, respectively,
      compared with a horizontal tubular gas aerator. Using an oscillating gas aerator
      and an oscillating baffle in a raceway pond increased the solution mass-transfer
      coefficient by 15% and decreased mixing time by 32%; consequently, microalgal
      biomass yield increased by 19%. 

PMID- 27035475
TI  - Pretreatment of corn stover for sugar production using a two-stage dilute acid
      followed by wet-milling pretreatment process.
AB  - A two-stage process was evaluated to increase sugar recovery. Firstly, corn
      stover was treated with dilute hydrochloric acid to recover the xylose, and then
      the residue was subjected to a wet-milling pretreatment. Dilute hydrochloric acid
      showed a high xylose recovery during the first stage. The optimal condition was
      120 degrees C and 40min for 0.7wt% dilute hydrochloric acid pretreatment followed
      by wet-milling pretreatment for 15min. The xylose and glucose yield were 81.0%
      and 64.0%, respectively, with a cellulase dosage at 3FPU/g of substrate. This two
      stage process was effective on account of the removal of hemicelluloses in the
      first stage and the delamination of cell wall in the second stage, increasing the
      possibility of adsorption of cellulose to enzymes, and resulting in a high sugar
      recovery with a very low enzyme loading. 

PMID- 27035476
TI  - Effect of biodegradation on thermogravimetric and chemical characteristics of
      hardwood and softwood by brown-rot fungus.
AB  - The thermogravimetric and chemical characterization of hardwood Eucalyptus
      urophylla (Ep) and softwood Pinus massoniana (Mp) pretreated by brown-rot fungus
      Gloeophyllum trabeum were investigated. The results indicated that the brown-rot
      fungus pretreatment can optimize the thermal decomposition and decrease the
      initiation temperatures (8-11 degrees C lower) of both the Ep and Mp pyrolysis.
      The mean activation energy values of the bio-treated samples were 29.7kJ/mol (for
      Ep) and 42.3kJ/mol (for Mp) lower than that of the un-treated samples at the
      conversion rate from 0.1 to 0.7 based on Flynn-Wall-Ozawa (FWO) method. After the
      bio-pretreatment, the required temperatures were lower (4-7 degrees C) for the
      pyrolysis rates of hemicellulose and cellulose in Mp reaching maximum and
      termination. However, the situation was just the opposite for Ep. The variations
      in chemical properties of hydrogen bonding, as well as the relative changes in
      lignin/carbohydrate composition of both wood species were also examined. 

PMID- 27035477
TI  - Microbial mechanisms of using enhanced ecological floating beds for eutrophic
      water improvement.
AB  - Enhanced ecological floating beds were implemented to reduce nutrient quantity
      and improve the water quality of a eutrophic lake. The results showed that
      average removal efficiencies of CODCr, total nitrogen, NH3-N and total phosphorus
      for Canna indica L. set-up were 23.1%, 15.3%, 18.1% and 19.4% higher,
      respectively, than that of the setup with only substrate, and 14.2%, 12.8%, 7.9%
      and 11.9% higher than Iris pseudacorus L. ecological floating bed. The microbial
      community structure had obvious differences between devices and low similarity;
      bacteria were mainly attached on the fiber filling. The microbial population was
      abundant at the start and end of the experiment. Shannon index of samples
      selected ranged from 0.85 to 1.05. The sequencing results showed that fiber
      filling collected most uncultured bacteria species and the majority of bacteria
      on the plant roots were beta-Proteobacteria and alpha-Proteobacteria. The co
      dominant species attaching to the filling and plant was Nitrosomonadaceae. 

PMID- 27035478
TI  - Co-production of biochar, bio-oil and syngas from halophyte grass (Achnatherum
      splendens L.) under three different pyrolysis temperatures.
AB  - In the present study, pyrolysis of Achnatherum splendens L. was performed under
      three different pyrolysis temperature (300, 500, and 700 degrees C) to
      investigate the characteristics of biochar, bio-oil, and syngas. Biochar yield
      decreased from 48% to 24%, whereas syngas yield increased from 34% to 54% when
      pyrolysis temperature was increased from 300 to 700 degrees C. Maximum bio-oil
      yield (27%) was obtained at 500 degrees C. The biochar were characterized for
      elemental composition, surface, and adsorption properties. The results showed
      that obtained biochar could be used as a potential soil amendment. The bio-oil
      and syngas co-products will be evaluated in the future as bioenergy sources.
      Overall, our results suggests that A. splendens L. could be utilized as a
      potential feedstock for biochar and bioenergy production through pyrolytic route.

PMID- 27035479
TI  - Comparative study of different alcoholate pretreatments for enhanced enzymatic
      hydrolysis of sugarcane bagasse.
AB  - Pretreatment of sugarcane bagasse (SCB) with alcoholates, sodium methoxide
      (CH3ONa), potassium methoxide (CH3OK) and sodium ethoxide (C2H5ONa), was
      investigated. Analyses of lignocellulose composition and enzymatic
      saccharification indicated that C2H5ONa showed the highest enzymatic efficiency
      of 102.1%. The response surface optimization of C2H5ONa pretreatment showed that
      under optimal conditions (4% of C2H5ONa, 121 degrees C, 1h), 65.4% of lignin was
      removed and the enzymatic efficiency reached 105.2%. Hydrolysis of SCB with
      cellulases and xylanase at a ratio of 4:1 showed the strongest synergism with
      reducing sugar production of 21g/L and conversion rates of cellulose and xylan
      reaching 110.4% and 94.5%, respectively. These results indicated that C2H5ONa is
      a promising alkali to pretreat SCB and the synergism between cellulases and
      xylanase has a significant effect on enzymatic saccharification of the pretreated
      SCB. 

PMID- 27035480
TI  - Lipase-catalyzed in-situ biosynthesis of glycerol-free biodiesel from
      heterotrophic microalgae, Aurantiochytrium sp. KRS101 biomass.
AB  - Heterotrophic microalgae, Aurantiochytrium sp. KRS101 had a large amount of lipid
      (56.8% total lipids). The cells in the culture medium were easily ruptured due to
      thin cell wall of Aurantiochytrium sp., which facilitated in-situ fatty acid
      methyl esters (FAMEs) production directly from biomass. The harvested biomass had
      a high content of free fatty acids (FFAs), which was advantageous for glycerol
      free FAMEs production. FAMEs were directly produced from Aurantiochytrium sp.
      KRS101 biomass (48.4% saponifiable lipids) using Novozyme 435-catalyzed in-situ
      esterification in dimethyl carbonate (DMC). DMC was used as a lipid extraction
      reagent, acyl acceptor and reaction medium. A 433.09mg FAMEs/g biomass was
      obtained with 89.5% conversion under the optimal condition: DMC to biomass ratio
      of 5:1 (v/w) and enzyme to biomass ratio of 30% (w/w) at 50 degrees C for 12h.
      Glycerol could not be detected in the produced FAMEs. 

PMID- 27035481
TI  - Biological carbon monoxide conversion to acetate production by mixed culture.
AB  - To utilize waste CO for mixed culture gas fermentation, carbon sources (CO, CO2)
      and pH were optimized in the batch system to find out the center point and
      boundary of response surface method (RSM) for higher acetate (HAc) production
      (center points: 25% CO, 40% CO2, and pH 8). The concentrations of CO and CO2, and
      pH had significant effects on acetate production, but the pH was the most
      significant on the HAc production. The optimum condition for HAc production in
      the gas fermentation was 20.81% CO, 41.38% CO2, 37.81% N2, and pH 7.18. The
      continuous gas fermentation under the optimum condition obtained 1.66g/L of cell
      DW, 23.6g/L HAc, 3.11g/L propionate, and 3.42g/L ethanol. 

PMID- 27035482
TI  - Multiscale characteristics dynamics of hydrochar from hydrothermal conversion of
      sewage sludge under sub- and near-critical water.
AB  - Dewatered sewage sludge was upgraded to hydrochar using hydrothermal conversion
      in sub- and near-critical water. Three characteristic temperature regimes
      responsible for the upgrading were identified. Drastic hydrolysis of
      carbohydrates, amide II or secondary amines occurred at 200 degrees C while
      noticeable decarboxylation initiated above 260 degrees C. Elevated temperature
      improved porosity but did not induce higher surface area. Aliphatic C was mainly
      transformed to aromatic hydrocarbon rather than aromatic C-O in subcritical
      water, whereas COO/N-CO and aromatic C-O were decomposed to carbohydrate C at 380
      degrees C. Below 300 degrees C, carbon functionalities in hydrochars were
      thermally stable and faster decomposition of N than C-(C,H) resulted in dramatic
      decline of N/C. Above 300 degrees C, C-H was gradually polymerized to aromatic C
      (C,H) which was considerably transformed to C-(O,N) and C-H at 380 degrees C. CaO
      favored intense destruction of aromatic C-C/C-H, anomeric O-C-O, C-H and C-(O,N)
      functionalities but introduced more aromatic C-O and OC-O. 

PMID- 27035483
TI  - Effect of low temperature on highly unsaturated fatty acid biosynthesis in
      activated sludge.
AB  - Low temperature is a limiting factor for the microbial activity of activated
      sludge for sewage treatment plant in winter. Highly unsaturated fatty acid (UFA)
      biosynthesis, phospholipid fatty acid (PLFA) constituents and microbial structure
      in activated sludge at low temperature were investigated. Over 12 gigabases of
      metagenomic sequence data were generated with the Illumina HiSeq 2000 platform.
      The result showed 43.11% of phospholipid fatty acid (PLFA) in the activated
      sludge participated in UFA biosynthesis, and gamma-Linolenic could be converted
      to Arachidonic acid at low temperature. The highly UFA biosynthesis in activated
      sludge was n-6 highly UFA biosynthesis, rather than n-3 highly UFA biosynthesis.
      The microbial community structures of activated sludge were analyzed by PLFA and
      high-throughput sequencing (HiSeq) simultaneously. Acidovorax, Pseudomonas,
      Flavobacterium and Polaromonas occupied higher percentage at 5 degrees C, and
      genetic changes of highly UFA biosynthesis derived from microbial community
      structures change. 

PMID- 27035484
TI  - Kinetic and energy production analysis of pyrolysis of lignocellulosic biomass
      using a three-parallel Gaussian reaction model.
AB  - The kinetic and energy productions of pyrolysis of a lignocellulosic biomass were
      investigated using a three-parallel Gaussian distribution method in this work.
      The pyrolysis experiment of the pine sawdust was performed using a
      thermogravimetric-mass spectroscopy (TG-MS) analyzer. A three-parallel Gaussian
      distributed activation energy model (DAEM)-reaction model was used to describe
      thermal decomposition behaviors of the three components, hemicellulose, cellulose
      and lignin. The first, second and third pseudocomponents represent the fractions
      of hemicellulose, cellulose and lignin, respectively. It was found that the model
      is capable of predicting the pyrolysis behavior of the pine sawdust. The
      activation energy distribution peaks for the three pseudo-components were
      centered at 186.8, 197.5 and 203.9kJmol(-1) for the pine sawdust, respectively.
      The evolution profiles of H2, CH4, CO, and CO2 were well predicted using the
      three-parallel Gaussian distribution model. In addition, the chemical composition
      of bio-oil was also obtained by pyrolysis-gas chromatography/mass spectrometry
      instrument (Py-GC/MS). 

PMID- 27035485
TI  - Marking a New Understanding of Climate and Health.

PMID- 27035486
TI  - Oral Psoriasis: An Overlooked Enigma.
AB  - Although cutaneous psoriasis is common, the existence of its manifestations in
      the oral cavity has been questioned. The definitive diagnosis of oral psoriasis
      can be challenging due to the variability of presentations, and overlapping
      clinical and histological features with a number of other conditions as well as
      the lack of consensus. We review oral psoriasis, noting its variable clinical
      appearance, delineate the differential diagnosis, and discuss management
      strategies. 

PMID- 27035487
TI  - Supervised domain adaptation of decision forests: Transfer of models trained in
      vitro for in vivo intravascular ultrasound tissue characterization.
AB  - In this paper, we propose a supervised domain adaptation (DA) framework for
      adapting decision forests in the presence of distribution shift between training
      (source) and testing (target) domains, given few labeled examples. We introduce a
      novel method for DA through an error-correcting hierarchical transfer relaxation
      scheme with domain alignment, feature normalization, and leaf posterior
      reweighting to correct for the distribution shift between the domains. For the
      first time we apply DA to the challenging problem of extending in vitro trained
      forests (source domain) for in vivo applications (target domain). The proof-of
      concept is provided for in vivo characterization of atherosclerotic tissues using
      intravascular ultrasound signals, where presence of flowing blood is a source of
      distribution shift between the two domains. This potentially leads to
      misclassification upon direct deployment of in vitro trained classifier, thus
      motivating the need for DA as obtaining reliable in vivo training labels is often
      challenging if not infeasible. Exhaustive validations and parameter sensitivity
      analysis substantiate the reliability of the proposed DA framework and
      demonstrates improved tissue characterization performance for scenarios where
      adaptation is conducted in presence of only a few examples. The proposed method
      can thus be leveraged to reduce annotation costs and improve computational
      efficiency over conventional retraining approaches.

PMID- 27035488
TI  - Synaptic compartmentalization by micropatterned masking of a surface adhesive cue
      in cultured neurons.
AB  - Functions of neuronal circuit are fundamentally modulated by its quality and
      quantity of connections. Assessment of synapse, the basic unit for a neuronal
      connection, is labor-intensive and time-consuming in conventional culture
      systems, due to the small size and the spatially random distribution. In the
      present study, we propose a novel 'synapse compartmentalization' culture system,
      in which synapses are concentrated at controlled locations. We fabricated a
      negative dot array pattern by coating the entire surface with poly-l-lysine (PLL)
      and subsequent microcontact printing of 1) substrates which mask positive charge
      of PLL (Fc, BSA and laminin), or 2) a chemorepulsive protein (Semaphorin 3F-Fc).
      By combination of physical and biological features of these repulsive substrates,
      functional synapses were robustly concentrated in the PLL-coated dots. This
      synapse compartmentalization chip can be combined with the various high
      throughput assay formats based on the synaptic morphology and function.
      Therefore, this quantifiable and controllable dot array pattern by microcontact
      printing will be potential useful for bio-chip platforms for the high-density
      assays used in synapse-related neurobiological studies.

PMID- 27035489
TI  - Traumatic Brain Injury Studies in Britain during World War II.
AB  - As a result of the wartime urgency to understand, prevent, and treat patients
      with traumatic brain injury (TBI) during World War II (WWII), clinicians and
      basic scientists in Great Britain collaborated on research projects that included
      accident investigations, epidemiologic studies, and development of animal and
      physical models. Very quickly, investigators from different disciplines shared
      information and ideas that not only led to new insights into the mechanisms of
      TBI but also provided very practical approaches for preventing or ameliorating at
      least some forms of TBI. Neurosurgeon Hugh Cairns (1896-1952) conducted a series
      of influential studies on the prevention and treatment of head injuries that led
      to recognition of a high rate of fatal TBI among motorcycle riders and
      subsequently to demonstrations of the utility of helmets in lowering head injury
      incidence and case fatality. Neurologists Derek Denny-Brown (1901-1981) and
      (William) Ritchie Russell (1903-1980) developed an animal model of TBI that
      demonstrated the fundamental importance of sudden acceleration (i.e., jerking) of
      the head in causing concussion and forced a distinction between head injury
      associated with sudden acceleration/deceleration and that associated with crush
      or compression. Physicist A.H.S. Holbourn (1907-1962) used theoretical arguments
      and simple physical models to illustrate the importance of shear stress in TBI.
      The work of these British neurological clinicians and scientists during WWII had
      a strong influence on subsequent clinical and experimental studies of TBI and
      also eventually resulted in effective (albeit controversial) public health
      campaigns and legislation in several countries to prevent head injuries among
      motorcycle riders and others through the use of protective helmets. Collectively,
      these studies accelerated our understanding of TBI and had subsequent important
      implications for both military and civilian populations. As a result of the
      wartime urgency to understand, prevent, and treat patients with TBI during WWII,
      clinicians and basic scientists collaborated on research projects that none of
      them would likely have pursued without these unique circumstances. Very quickly,
      there was a sharing of information and ideas that not only led to new insights
      into the mechanisms of TBI but also provided very practical approaches for
      preventing or ameliorating at least some forms of TBI. Investigators in Great
      Britain, in particular, pioneered accident investigations, performed
      epidemiologic studies, and developed animal and physical models that accelerated
      our understanding of TBI and had subsequent important implications for both
      military and civilian populations. 

PMID- 27035490
TI  - Low-Dose Imipramine for the Treatment of Panic Disorder During Postpartum Period:
      A Retrospective Analysis of 6 Cases.

PMID- 27035491
TI  - Quetiapine Associated With Angioedema.

PMID- 27035492
TI  - Multiple Long-Acting Injectable Antipsychotics for Treatment-Resistant
      Schizophrenia: Case Report.

PMID- 27035493
TI  - Sleep-Related Eating Disorder Associated With Risperidone: An Adolescent Case.

PMID- 27035494
TI  - Post-Lyme Syndrome-Associated Polyneuropathy Treated With Immune Immunoglobulin
      and a Luteolin-Containing Formulation.

PMID- 27035495
TI  - Quercetin as an Augmentation Agent in Schizophrenia.

PMID- 27035496
TI  - A Case of Emergent Restless Legs Syndrome With Lurasidone Therapy.

PMID- 27035497
TI  - Posterolaterally displaced and flexion-type supracondylar fractures are
      associated with a higher risk of open reduction.
AB  - To identify factors predictive of the risk of conversion from closed to open
      reduction. International Classification of Disease-9 codes were used to identify
      completely displaced pediatric supracondylar humerus fractures that were
      subjected to planned closed reduction and percutaneous pinning. Clinical and
      radiographic variables were retrospectively collected. Compared with posterior
      extension fractures, flexion (risk ratio: 34.1, 95% confidence interval: 8.1
      143.6, P<0.0001) and posterolateral extension (risk ratio: 6.0, 95% confidence
      interval: 1.3-27.5, P=0.0221) fractures were significantly more likely to undergo
      conversion from closed to open reduction. The direction of displacement should be
      considered during the preoperative evaluation of supracondylar fractures. 

PMID- 27035498
TI  - Omalizumab's Impact on Total and Allergen-Specific IgE Levels: A Polyclonal
      Story.

PMID- 27035499
TI  - Is There a Role for Arnica and Bromelain in Prevention of Post-Procedure
      Ecchymosis or Edema? A Systematic Review of the Literature.
AB  - BACKGROUND: The management of postprocedure skin care is of significant interest
      to dermatologists and other physicians. Ecchymosis and edema are common temporary
      postprocedure unwanted effects. Two botanically-derived products, arnica and
      bromelain, are used internationally by physicians to limit ecchymosis and edema
      that occur secondary to cosmetic, laser, and surgical skin procedures. OBJECTIVE:
      The authors review the published literature and provide evidence-based
      recommendations on arnica and bromelain for prevention and treatment of
      postprocedure ecchymosis and edema. METHODS AND MATERIALS: A search of the
      computerized bibliographic databases Medline, EMBASE, Scopus, and CINAHL was
      performed on March 23, 2015. The key terms used were "arnica," and "bromelain."
      RESULTS: This review contains clinical trials that evaluated prevention and/or
      treatment of postprocedure ecchymosis or edema with oral arnica (11), topical
      arnica (2), and oral bromelain (7). No studies on topical bromelain were found.
      Clinical trials on arnica and bromelain have demonstrated mixed results. Some
      randomized controlled trials reported improvement postprocedure with arnica
      (4/13) and bromelain (5/7). CONCLUSION: Based upon published studies, there is
      insufficient data to support use of arnica and bromelain post procedure, and the
      authors recommend additional research to determine the efficacy and safety of
      arnica and bromelain to prevent and/or treat ecchymosis and edema in patients.

PMID- 27035500
TI  - Hidden Transection of Follicular Unit Extraction in Donor Site.
AB  - BACKGROUND: When calculating the transection rate in follicular unit extraction
      (FUE), many surgeons did not consider damages that may arise in the donor site
      through FUE punching. OBJECTIVE: The authors investigated what changes and/or
      damages are happened to the hair follicles surrounding a punched hole. MATERIALS
      AND METHODS: Two to 4 study boxes were marked on the donor strip and 8 follicular
      units were harvested using FUE from each study box. Follicular unit extraction
      was performed by the expert for 10 patients and by the beginner for 10 patients.
      After the strip harvesting, each study box was separated. Then, the 2 cross
      sections along the punched line and follicular units obtained from each study box
      were analyzed under a 20-power digital microscope. RESULTS: The authors found
      various transections through this analysis. Among them, some transections were
      hidden under the scalp surface, keeping the shaft alignment. The authors named
      this occurrence "hidden transection." Although 2 surgeons harvested with similar
      transection rate, there was a significant difference in hidden transection rate:
      2% for the expert and 8% for the beginner. CONCLUSION: The main finding of this
      study is that a correct way to calculate the real-transection rate in FUE is to
      consider both extracted follicular transection and hidden transection.

PMID- 27035501
TI  - Randomized Placebo-Controlled, Double-Blind, Half-Head Study to Assess the
      Efficacy of Platelet-Rich Plasma on the Treatment of Androgenetic Alopecia.
AB  - BACKGROUND: Platelet-rich plasma (PRP) was identified as having a beneficial
      effect in alopecia and has been postulated as a new therapy for androgenetic
      alopecia (AGA). OBJECTIVE: To assess the efficacy of PRP for the treatment of
      AGA. MATERIALS AND METHODS: This was a randomized, placebo-controlled, double
      blind study in 25 patients with AGA. Platelet-rich plasma was injected in half
      head and the other half-head with placebo. Each patient received a total of 3
      treatments of PRP, 1 month apart. RESULTS: Six months after the first treatment
      with PRP, significant differences were seen in mean anagen hairs (67.6 +/- 13.1),
      telogen hairs (32.4 +/- 13.1), hair density (179.9 +/- 62.7), and terminal hair
      density (165.8 +/- 56.8) when compared with baseline (p < .05). Platelet-rich
      plasma was also found to increase hair density when comparing with the control
      side (p < .05). For the first time, the authors found a correlation between
      anagen hairs and patients >40 years and beginning of AGA >=25 years old (p < .05)
      and hair density and male sex, age <=40 years, positive family history of AGA and
      >10 years of duration of the disease (p < 0.05). CONCLUSION: Application of PRP
      showed a positive effect on AGA and could be regarded as an adjuvant therapy for
      AGA.

PMID- 27035502
TI  - Repair of a Defect of the Lateral Suprabrow.

PMID- 27035503
TI  - Polytypism and unexpected strong interlayer coupling in two-dimensional layered
      ReS2.
AB  - Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both
      scientific interest and application potential, offer one more dimension than
      isotropic 2D materials to tune their physical properties. Various physical
      properties of 2D multi-layer materials are modulated by varying their stacking
      orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide
      (ReS2), a representative anisotropic 2D material, was expected to be randomly
      stacked and lack interlayer coupling. Here, we demonstrate two stable stacking
      orders, namely isotropic-like (IS) and anisotropic-like (AI) N layer (NL, N > 1)
      ReS2 are revealed by ultralow- and high-frequency Raman spectroscopy,
      photoluminescence and first-principles density functional theory calculation. Two
      interlayer shear modes are observed in AI-NL-ReS2 while only one shear mode
      appears in IS-NL-ReS2, suggesting anisotropic- and isotropic-like stacking orders
      in IS- and AI-NL-ReS2, respectively. This explicit difference in the observed
      frequencies identifies an unexpected strong interlayer coupling in IS- and AI-NL
      ReS2. Quantitatively, the force constants of them are found to be around 55-90%
      of those of multilayer MoS2. The revealed strong interlayer coupling and
      polytypism in multi-layer ReS2 may stimulate future studies on engineering
      physical properties of other anisotropic 2D materials by stacking orders. 

PMID- 27035504
TI  - Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous
      leukemia K562/ADM cells by downregulating P-gp and MRP-1.
AB  - Multidrug resistance (MDR) of leukemia cells is a major obstacle in
      chemotherapeutic treatment. The high expression and constitutive activation of P
      glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) have been reported
      to play a vital role in enhancing cell resistance to anticancer drugs in many
      tumors. The present study aimed to investigate the reversal of MDR by silencing
      homeobox A10 (HOXA10) in adriamycin (ADR)-resistant human chronic myelogenous
      leukemia (CML) K562/ADM cells by modulating the expression of P-gp and MRP-1.
      K562/ADM cells were stably transfected with HOXA10-targeted short hairpin RNA
      (shRNA). The results of reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) and western blot analysis showed that the mRNA and protein
      expression of HOXA10 was markedly suppressed following transfection with a shRNA
      containing vector. The sensitivity of the K562/ADM cells to ADR was enhanced by
      the silencing of HOXA10, due to the increased intracellular accumulation of ADR.
      The accumulation of ADR induced by the silencing of HOXA10 may be due to the
      downregulation of P-gp and MRP-1. Western blot analysis revealed that
      downregulating HOXA10 inhibited the protein expression of P-gp and MRP-1. Taken
      together, these results suggest that knockdown of HOXA10 combats resistance and
      that HOXA10 is a potential target for resistant human CML.

PMID- 27035505
TI  - Epigenome-wide search for association of serum 25-hydroxyvitamin D concentration
      with leukocyte DNA methylation in a large cohort of older men.
AB  - AIM: We aimed for an epigenome-wide identification of vitamin D-associated CpG
      sites in leukocyte DNA. MATERIALS & METHODS: Infinium HumanMethylation450BeadChip
      measurements in 402 Caucasian older men were evaluated for significant
      association with 25-hydroxy-vitamin (25(OH)D) using Spearman's correlation and
      median regression to adjust for confounding variables. A cross-validation
      approach as well as a bootstrapping procedure were implemented to determine the
      replicability of significant associations. Multiple testing was corrected for by
      Benjamini-Hochberg or Bonferroni. RESULTS: Although in the screening subcohorts
      significant associations of DNAm with 25(OH)D were observed in the validation
      cohorts these associations were not replicated after adjustment for potential
      confounders. At none of the 361,945 CpGs a significant association of DNAm with
      25(OH)D was found in all 100 random bootstrap samples, but in comparison at 462
      CpGs for the well-established association with age. CONCLUSION: Leukocyte DNAm
      was not associated with 25(OH)D levels after validation and consideration of
      confounders.

PMID- 27035506
TI  - Biomechanics of transvertebral screw fixation in the thoracic spine: an in vitro
      study.
AB  - OBJECTIVE Transvertebral screws provide stability in thoracic spinal fixation
      surgeries, with their use mainly limited to patients who require a pedicle screw
      salvage technique. However, the biomechanical impact of transvertebral screws
      alone, when they are inserted across 2 vertebral bodies, has not been studied. In
      this study, the authors assessed the stability offered by a transvertebral screw
      construct for posterior instrumentation and compared its biomechanical
      performance to that of standard bilateral pedicle screw and rod (PSR) fixation.
      METHODS Fourteen fresh human cadaveric thoracic spine segments from T-6 to T-11
      were divided into 2 groups with similar ages and bone quality. Group 1 received
      transvertebral screws across 2 levels without rods and subsequently with
      interconnecting bilateral rods at 3 levels (T8-10). Group 2 received bilateral
      PSR fixation and were sequentially tested with interconnecting rods at T7-8 and
      T9-10, at T8-9, and at T8-10. Flexibility tests were performed on intact and
      instrumented specimens in both groups. Presurgical and postsurgical O-arm 3D
      images were obtained to verify screw placement. RESULTS The mean range of motion
      (ROM) per motion segment with transvertebral screws spanning 2 levels compared
      with the intact condition was 66% of the mean intact ROM during flexion-extension
      (p = 0.013), 69% during lateral bending (p = 0.015), and 47% during axial
      rotation (p < 0.001). The mean ROM per motion segment with PSR spanning 2 levels
      compared with the intact condition was 38% of the mean intact ROM during flexion
      extension (p < 0.001), 57% during lateral bending (p = 0.007), and 27% during
      axial rotation (p < 0.001). Adding bilateral rods to the 3 levels with
      transvertebral screws decreased the mean ROM per motion segment to 28% of intact
      ROM during flexion-extension (p < 0.001), 37% during lateral bending (p < 0.001),
      and 30% during axial rotation (p < 0.001). The mean ROM per motion segment for
      PSR spanning 3 levels was 21% of intact ROM during flexion-extension (p < 0.001),
      33% during lateral bending (p < 0.001), and 22% during axial rotation (p <
      0.001). CONCLUSIONS Biomechanically, fixation with a novel technique in the
      thoracic spine involving transvertebral screws showed restoration of stability to
      well within the stability provided by PSR fixation. 

PMID- 27035507
TI  - The use of spine stereotactic radiosurgery for oligometastatic disease.
AB  - OBJECTIVE The authors investigated the outcomes following spine stereotactic
      radiosurgery (SSRS) for patients with oligometastatic disease of the spine.
      METHODS The study was a secondary analysis of 38 of 209 patients enrolled in 2
      separate institutional Phase I/II prospective protocols and treated with SSRS
      between 2002 and 2011. Of these 38 patients, 33 (87%) were treated for a solitary
      spine metastasis, with no other history of metastatic disease. SSRS was
      prescribed to 24 Gy in 1 fraction (8%), 18 Gy in 1 fraction (18%), 16 Gy in 1
      fraction (11%), 27 Gy in 3 fractions (53%), 30 Gy in 5 fractions (8%), or 20 Gy
      in 5 fractions (3%). Seventeen patients (45%) received prior conventional
      external beam radiation therapy. RESULTS The median overall survival (OS) was
      75.7 months, and the 2- and 5-year OS rates were 84% and 60%, respectively. In
      multivariate analysis, patients who had prior spine surgery and a better
      Karnofsky Performance Scale score had an improved OS (HR 0.16, 95% CI 0.05-0.52,
      p < 0.01, and HR 0.33, 95% CI 0.13%-0.84%, p = 0.02, respectively), and those who
      had undergone prior radiation therapy had a worse OS (HR 3.6, 95% CI 1.2%-10%, p
      = 0.02). The 1-, 2-, and 5-year local progression-free survival rates were 85%,
      82%, and 78%, respectively. The median time to systemic therapy modification was
      41 months. Two patients (5%) experienced late Grade 3-4 toxicity. CONCLUSIONS
      Patients with oligometastatic disease of the spine treated with SSRS can
      experience long-term survival and a long time before needing a modification in
      systemic therapy. In addition, SSRS leads to excellent local control and minimal
      late toxicity. 

PMID- 27035508
TI  - Editorial: Vancomycin, bone growth, and wound healing.

PMID- 27035509
TI  - Letter to the Editor: Early achievements of Hans Brun in the surgery of
      intramedullary tumors.

PMID- 27035510
TI  - The effect of vancomycin powder on bone healing in a rat spinal rhBMP-2 model.
AB  - OBJECTIVE This study aims to quantify the impact of vancomycin powder application
      on new bone formation and spine fusion rates in a rat posterolateral arthrodesis
      model. METHODS Thirty-six female Sprague-Dawley rats underwent a posterolateral
      lumbar spinal fusion (PLF) at the L-4 and L-5 vertebrae. Fusion was elicited via
      implantation of an absorbable collagen sponge containing 3 ug rhBMP-2. Rats were
      divided into 3 groups: no vancomycin (control), standard-dose vancomycin, and
      high-dose vancomycin, based on what was applied to the fusion bed. Clinical
      studies typically describe the application of 1 g vancomycin into the surgical
      wound. Presuming an average individual patient weight of 70 kg, a weight-based
      equivalent dose of vancomycin powder was applied subfascially in the PLF model
      constituting a "standard-dose" treatment group (14.3 mg/kg, n = 12). To determine
      whether there is a critical threshold beyond which vancomycin increases the risk
      of pseudarthrosis, a 10-fold higher dose was administered to a "high-dose"
      treatment group (143 mg/kg, n = 12). No vancomycin powder was applied to the
      surgical site in the control group (n = 12). Fusion was evaluated with plain
      radiographs at 4 and 8 weeks after surgery. The spines were harvested after the 8
      week radiographs were obtained and evaluated using manual palpation, microCT
      analysis, and histological analysis. RESULTS Radiographs demonstrated equivalent
      bridging bone formation in all groups. No significant differences in fusion
      scores were seen in the standard-dose (mean 2.25) or high-dose (2.13) treatment
      groups relative to untreated control animals (1.78). Similarly, fusion rates did
      not differ significantly different between vancomycin-treated animals (100% for
      both groups) and control animals (92%). Quantification of new bone formation via
      microCT imaging revealed no significant between-groups differences in the volume
      of newly regenerated bone (control vs standard-dose vancomycin, p = 0.57; control
      vs high-dose vancomycin, p = 0.53). CONCLUSIONS This is the first in vivo study
      to specifically address the development of pseudarthrosis after intrawound
      application of vancomycin during fusion surgery. Our results demonstrate that
      vancomycin powder does not inhibit fusion rates at a dose that is the weight
      percentage equivalent of what is routinely used by surgeons. Moreover, bone
      formation and fusion rates were not reduced even after administration of a
      vancomycin dose that is 10-fold higher than that which is typically administered
      clinically. Our findings suggest that if there is a critical threshold above
      which vancomycin inhibits bone healing, such a dose is out of the range which
      might be considered reasonable for clinical use. 

PMID- 27035511
TI  - Nemo-like kinase regulates the expression of vascular endothelial growth factor
      (VEGF) in alveolar epithelial cells.
AB  - The canonical Wnt signaling can be silenced either through beta-catenin-mediated
      ubiquitination and degradation or through phosphorylation of Tcf and Lef by nemo
      like kinase (NLK). In the present study, we generated NLK deficient animals and
      found that these mice become cyanotic shortly before death because of lung
      maturation defects. NLK-/- lungs exhibited smaller and compressed alveoli and the
      mesenchyme remained thick and hyperplastic. This phenotype was caused by
      epithelial activation of vascular endothelial growth factor (VEGF) via
      recruitment of Lef1 to the promoter of VEGF. Elevated expression of VEGF and
      activation of the VEGF receptor through phosphorylation promoted an increase in
      the proliferation rate of epithelial and endothelial cells. In summary, our study
      identifies NLK as a novel signaling molecule for proper lung development through
      the interconnection between epithelial and endothelial cells during lung
      morphogenesis. 

PMID- 27035512
TI  - The effects of lumbar extensor strength on disability and mobility in patients
      with persistent low back pain.
AB  - BACKGROUND: It is assumed that low back pain patients who use pain-avoiding
      immobilizing strategies may benefit from specific back flexion and extension
      exercises aimed at reducing sagittal lumbar hypomobility. The aim of this study
      was to test this potential working mechanism in chronic low back pain patients
      undergoing lumbar extensor strengthening training. METHODS: A single-group
      prospective cohort design was used in this study. Patients with persistent low
      back complaints for at least 2 years were recruited at a specialized physical
      therapy clinics center. They participated in a progressive 11-week lumbar
      extensor strength training program, once a week. At baseline, sagittal lumbar
      mobility in flexion and extension was measured with a computer-assisted
      inclinometer. Self-rated pain intensity was measured using a visual analogue
      scale, back-specific functional status was assessed with the Quebec Back Pain
      Disability Scale and the Patient Specific Complains questionnaire. RESULTS:
      Statistically significant improvements were found in pain (28% decrease) and
      functional disability (23% to 36% decrease). Most progress was seen in the first
      5 treatment weeks. Lumbar mobility in flexion showed non-significant increases
      over time (+12%). Pre-post treatment changes in flexion and extension mobility
      did not contribute significantly to the models. The retained factors together
      explained 15% to 48% of the variation in outcome. CONCLUSIONS: Specific lumbar
      strengthening showed clinically relevant improvements in pain and disability in
      patients with persistent chronic low back pain. These improvements did not
      necessarily relate to improvements in lumbar mobility. Parameters representing
      other domains of adaptations to exercise may be needed to evaluate the effects of
      back pain management.

PMID- 27035513
TI  - Systematic review of clinical adverse events reported after acute intravenous
      lipid emulsion administration.
AB  - BACKGROUND: Intravenous lipid emulsions (ILEs) were initially developed to
      provide parenteral nutrition. In recent years, ILE has emerged as a treatment for
      poisoning by local anesthetics and various other drugs. The dosing regimen for
      the clinical toxicology indications differs significantly from those used for
      parenteral nutrition. The evidence on the efficacy of ILE to reverse acute
      toxicity of diverse substances consists mainly of case reports and animal
      experiments. Adverse events to ILE are important to consider when clinicians need
      to make a risk/benefit analysis for this therapy. METHODS: Multiple publication
      databases were searched to identify reports of adverse effects associated with
      acute ILE administration for either treatment of acute poisoning or parenteral
      nutrition. Articles were selected based on pre-defined criteria to reflect acute
      use of ILE. Experimental studies and reports of adverse effects as a complication
      of long-term therapy exceeding 14 days were excluded. RESULTS: The search
      identified 789 full-text articles, of which 114 met the study criteria. 27 were
      animal studies, and 87 were human studies. The adverse effects associated with
      acute ILE administration included acute kidney injury, cardiac arrest,
      ventilation perfusion mismatch, acute lung injury, venous thromboembolism,
      hypersensitivity, fat embolism, fat overload syndrome, pancreatitis,
      extracorporeal circulation machine circuit obstruction, allergic reaction, and
      increased susceptibility to infection. CONCLUSION: The emerging use of ILE
      administration in clinical toxicology warrants careful attention to its potential
      adverse effects. The dosing regimen and context of administration leading to the
      adverse events documented in this review are not generalizable to all clinical
      toxicology scenarios. Adverse effects seem to be proportional to the rate of
      infusion as well as total dose received. Further safety studies in humans and
      reporting of adverse events associated with ILE administration at the doses
      advocated in current clinical toxicology literature are needed.

PMID- 27035514
TI  - A constriction resistance model of conjugated polymer based piezoresistive
      sensors for electronic skin applications.
AB  - Human intervention can be replaced through the development of tools resulting
      from utilization of sensing devices possessing a wide range of applications
      including humanoid robots or remote and minimally invasive surgeries. Similar to
      the five human senses, sensors interface with their surroundings to stimulate a
      suitable response or action. The sense of touch which arises in human skin is
      among the most challenging senses to emulate due to its ultra high sensitivity.
      This has brought forth novel challenging issues to consider in the field of
      biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole
      (PPy) based hydrogel is developed as a resistive type pressure sensor with an
      intrinsically elastic microstructure stemming from three dimensional hollow
      spheres. It is shown that the electrical conductivity of the fabricated PPy based
      piezoresistive sensors is enhanced as a result of adding conductive fillers and
      therefore, endowing the sensors with a higher sensitivity. A semi-analytical
      constriction resistance based model accounting for the real contact area between
      the PPy hydrogel sensors and the electrode along with the dependency of the
      contact resistance change on the applied load is developed. The model is then
      solved using a Monte Carlo technique and its corresponding sensitivity is
      obtained. Comparing the results with their experimental counterparts, the
      proposed modeling methodology offers a good tracking ability.

PMID- 27035515
TI  - Longitudinal Predictive Validity of the DSM-5 Anxious Distress Specifier for
      Clinical Outcomes in a Large Cohort of Patients With Major Depressive Disorder.
AB  - OBJECTIVE: While the new DSM-5 anxious distress specifier is of great clinical
      importance, no evidence exists for its longitudinal predictive validity for
      clinical outcomes in patients with major depressive disorder (MDD). We examined
      the longitudinal validity of this specifier and validated it against DSM-IV-based
      comorbid anxiety disorder diagnoses. METHODS: Data are from 1,080 patients with
      current MDD at baseline (September 2004 to February 2007), of which 911
      participated in the 2-year follow-up (September 2006 to April 2009). Patients are
      from the Netherlands Study of Depression and Anxiety, which is an ongoing
      longitudinal cohort study, and were sampled from the community, primary care, and
      outpatient specialized care settings. The specifier was constructed in the
      existing sample by 5 matching self-report items. Predictive outcomes were 2-year
      chronicity, time to remission of MDD, and functional disability. Discriminant
      performance and convergent validity of the specifier were also assessed. RESULTS:
      The specifier was present in 54.2% of the sample. The specifier significantly
      outperformed anxiety disorders in predicting chronicity (OR = 1.96, P < .001, vs
      OR = 1.11, P = .49), time to remission of MDD (HR = 0.75, P = .002, vs HR = 0.94,
      P = .55), and functional disability (B = 10.03, P < .001, vs B = 2.53, P = .07).
      The specifier significantly discriminated in clinical characteristics, had
      convergent validity for anxiety characteristics, and poorly overlapped with DSM
      IV-based anxiety disorder diagnoses (Cohen kappa = .09). CONCLUSIONS: The short
      anxious distress specifier outperforms DSM-IV-based anxiety disorder diagnoses as
      a longitudinal predictor for clinical outcomes in patients with MDD.

PMID- 27035516
TI  - Optimal sequence of antisense DNA to silence YB-1 in lung cancer by use of a
      novel polysaccharide drug delivery system.
AB  - Silencing Y-box binding protein 1 (YB-1) can be an excellent target for cancer
      therapy and many lung cancer cells express the polysaccharide-recognition
      receptor Dectin-1. We designed a Dectin-1 targeting vehicle delivering YB-1
      antisense DNA. First, we selected five optimal antisense DNA sequences to silence
      YB-1 from among 153 candidates. We chose the sequence closest to the start codon
      (AS014), and attached dA40 to the 3' end; dA40 promotes complex formation with a
      beta-(1?3)-d-glucan called schizophyllan (SPG). The resultant complexes were
      applied to 12 human-oriented lung cancer cell lines, and cell viability was
      examined. The cell lines exhibited decreased viability and showed strong affinity
      to bind SPG, suggesting the AS014/SPG complex entered the cells via the Dectin-1
      mediated pathway. 

PMID- 27035517
TI  - First principles study of confinement effects for oxygen vacancies in BaZrO3
      (001) ultra-thin films.
AB  - In this contribution, we study possible confinement effects on the atomic and
      electronic structure, and phonon properties of neutral (V(O)(x) and fully charged
      (V(O)oxygen vacancies in BaZrO3 (001) ultra-thin films. First principles phonon
      calculations were performed as a function of film thickness (from 3 to 7 atomic
      planes) with two complementary DFT methods. The calculations reveal that for both
      types of vacancies the confinement effect is very short-range; for films
      containing 5 planes or more, the oxygen vacancy properties are predicted to be
      similar to those observed in the bulk material.

PMID- 27035518
TI  - Impact of multicellular tumor spheroids as an in vivo-like tumor model on
      anticancer drug response.
AB  - The incidence of colorectal cancer is higher in men than in women, amounting to
      15% of cancer-related diseases as a whole. As such, undesirable effects, arising
      from the administration of current chemotherapeutic agents (the FOLFIRI/FOLFOX
      combinations), which are exerted on the remaining non-cancerous tissues and/or
      cells, have contributed to the occurrence of resistance to multiple drugs, thus
      markedly reducing their efficacy. However, the delivery of chemotherapeutic
      agents may be improved and their action may be more selectively targeted to
      diseased tissues/cells by means of developing biotechnologies and nano
      techniques. Thus, the current focus is on creating biological tissue and related
      tumor models, by means of three-dimensional (3D) spheres, in an attempt to bridge
      the gap between results obtained in the pre-clinical phase and promising outcomes
      obtained in clinical trials. For this purpose, the characterization and use of so
      called 'multicellular tumor spheroids', may prove to be invaluable. In this
      study, we focus on describing the efficacy of a model 3D system as compared to
      the traditional 2D tumor spheres in determining drug response, highlighting a
      potentially greater effect of the drugs following the encapsulation of respective
      liposomes. The results obtained demonstrate the successful preparation of a
      suspension of liposomes loaded with folinic acid, oxaliplatin and 5-fluorouracil
      (5-FU), and loaded with meso-tetra (4-sulfonatophenyl) porphyrin. Following its
      use on HT-29 colorectal cancer cells, an important comparative reduction was
      noted in the viability of the HT-29 cells, demonstrating the efficacy of
      multicellular tumor spheroids carrying liposomes loaded with therapeutic drugs.
      These findings indicate that the method of drug encapsulation in liposomes may
      improve the treatment efficacy of chemotherapeutic agents. 

PMID- 27035519
TI  - Increased risk of new-onset depression in patients with traumatic brain injury
      and hyperlipidemia: the important role of statin medications.
AB  - OBJECTIVE: Depression is a common complication after traumatic brain injury
      (TBI). This study aimed to evaluate the risk of hyperlipidemia for new-onset
      depression after TBI and the role of statin medications using a longitudinal
      population database. METHOD: A matched longitudinal cohort study of 3,792
      subjects (1,264 TBI patients [ICD-9-CM code: 801-804 and 850-854] with
      preexisting hyperlipidemia [ICD-9-CM code: 272.0, 272.1, 272.2, 272.4] and 2,528
      age- and sex-matched TBI patients without hyperlipidemia) was conducted using the
      Taiwan Longitudinal Health Insurance Database from January 2001 to December 2008.
      The incidence and hazard ratios (HRs) for the development of new-onset depression
      (ICD-9-CM code: 296.2X-296.3X, 300.4, and 311.X) after TBI were compared between
      the 2 groups. RESULTS: The incidence rate of depression in TBI with preexisting
      hyperlipidemia was 136.61 per 10,000 person-years. TBI patients with preexisting
      hyperlipidemia had a 1.72-fold increased incidence rate ratio compared with those
      without hyperlipidemia (P = .0056). A Cox model showed hyperlipidemia to be an
      independent predictor of depression (HR = 1.61; 95% CI, 1.03-2.53). TBI patients
      with hyperlipidemia who were not treated with statins experienced a 1.95-fold
      incidence risk ratio (P = .0017) and higher risk of new-onset depression (HR =
      1.61; 95% CI, 1.03-2.53) compared to TBI patients without hyperlipidemia.
      CONCLUSIONS: Preexisting hyperlipidemia could be an independent predictor of new
      onset depression in TBI patients, and TBI patients with preexisting
      hyperlipidemia who were not treated with statins presented a higher risk of new
      onset depression than TBI patients without hyperlipidemia. Our findings may
      provide some insight into the important role of statin medications in the
      development of new-onset depression in patients with traumatic brain injury.

PMID- 27035521
TI  - A Diamond in the Rough.

PMID- 27035522
TI  - A Qualitative Inquiry on Palliative and End-of-Life Care Policy Reform.
AB  - BACKGROUND: There is increasing recognition of the role of palliative care (PC)
      in health care delivery, but priorities for state and federal policy to support
      PC are unclear and have sometimes engendered controversy. We canvassed experts to
      shed light on general recommendations for improving PC. OBJECTIVE: The study
      objective was to identify challenges to and potential solutions for promoting,
      adopting, and implementing policies that would support or expand high-quality PC.
      METHODS: Semistructured telephone interviews were used to solicit challenges to
      and potential solutions for promoting, adopting, and implementing policies that
      would support or expand high-quality PC. Interviews were analyzed using
      qualitative methods. The subjects were a purposive sample of 22 professional
      state and federal-level advocates who work in the field of aging and/or PC.
      RESULTS: Respondents identified four central challenges to advancing PC policies:
      (1) knowledge about PC in the health care setting, (2) cultural beliefs about PC,
      (3) payment/reimbursement for PC services, and (4) public understanding of PC. Of
      the wide range of solutions proposed by respondents, we present the eight most
      frequently discussed solutions to these challenges targeted towards policymakers,
      health care professionals, research, and the general public. Respondents'
      understanding of the relationships between problems and solutions revealed many
      dependencies and interconnectedness. CONCLUSIONS: A qualitative approach of
      querying experts identified multiple significant challenges to improving and
      expanding PC, most of which are acknowledged in existing consensus statements.
      Proposed solutions were more numerous and diffuse than descriptions of the
      problems, signaling the need for further consensus building around actionable
      policy, and better understanding of how to advance a PC policy agenda.

PMID- 27035523
TI  - Measurement of Heme Ruffling Changes in MhuD Using UV-vis Spectroscopy.
AB  - For decades it has been known that an out-of-plane ruffling distortion of heme
      perturbs its UV-vis absorption (Abs) spectrum, but whether increased ruffling
      induces a red or blue shift of the Soret band has remained a topic of debate.
      This debate has been resolved by the spectroscopic and computational
      characterization of Mycobacterium tuberculosis MhuD presented here, an enzyme
      that converts heme, oxygen, and reducing equivalents to nonheme iron and
      mycobilin. W66F and W66A MhuD have been characterized using (1)H nuclear magnetic
      resonance, Abs, and magnetic circular dichroism spectroscopies, and the data have
      been used to develop an experimentally validated theoretical model of ruffled,
      ferric heme. The PBE density functional theory (DFT) model that has been
      developed accurately reproduces the observed spectral changes from wild type
      enzyme, and the underlying quantum mechanical origins of these ruffling-induced
      changes were revealed by analyzing the PBE DFT description of the electronic
      structure. Small amounts of heme ruffling have no influence on the energy of the
      Q-band and blue-shift the Soret band due to symmetry-allowed mixing of the Fe
      3dxy and porphyrin a2u orbitals. Larger amounts of ruffling red-shift both the Q
      and Soret bands due to disruption of pi-bonding within the porphyrin ring.

PMID- 27035524
TI  - One-Step Fabrication of Microchannels Lined with a Metal Oxide Coating.
AB  - We demonstrate a simple, single-step method for metal/metal oxide coating on
      interior walls of microchannels in an elastomeric material like PDMS, which is
      the mainstay of microfluidic devices. The fabrication process involves
      electrodeposition of cuprous oxide on a metallic wire or a sheet, embedding it
      inside a PDMS matrix along with the cross-linker, curing and then swelling the
      PDMS elastomer, and finally pulling out the template metal wire or the metal
      sheet from the PDMS matrix. Stronger attachment of the metal oxide layer to PDMS
      allows the transfer of the metal oxide coating originally present on the template
      surface (wire or sheet) to the channel wall resulting in a microchannel/microslit
      lined with the metal/metal oxide layer. In view of the catalytic activity
      associated with transition metal oxides, this simple method offers a cost
      effective and versatile technique to fabricate microfluidic and lab-on-a-chip
      devices which can be utilized as microcatalytic reactors or chemical filters. As
      a proof of concept, we have successfully tested the metal oxide coated
      microchannels and microslits as active sites for adsorption of iodide ions.

PMID- 27035525
TI  - Land claim and loss of tidal flats in the Yangtze Estuary.
AB  - Tidal flats play a critical role in supporting biodiversity and in providing
      ecosystem services but are rapidly disappearing because of human activities. The
      Yangtze Estuary is one of the world's largest alluvial estuaries and is adjacent
      to the most developed economic zone in China. Using the Yangtze Estuary as a
      study region, we developed an automatic algorithm to estimate tidal flat areas
      based on the Land Surface Water Index and the Normalized Difference Vegetation
      Index. The total area of tidal flats in the Yangtze Estuary has decreased by 36%
      over the past three decades, including a 38% reduction in saltmarshes and a 31%
      reduction in barren mudflats. Meanwhile, land claim has accumulated to 1077
      km(2), a value that exceeds the area of the remaining tidal flats. We divided the
      Yangtze Estuary into Shanghai and Jiangsu areas, which differ in riverine
      sediment supply and tidal flat management patterns. Although land claim has
      accelerated in both areas, the decline in tidal flat area has been much greater
      in Jiangsu than in Shanghai because of abundant supplies of sediment and
      artificial siltation in the latter area. The results highlight the need for
      better coastal planning and management based on tidal flat dynamics.

PMID- 27035526
TI  - Vagus nerve electrical stimulation inhibits serum levels of S100A8 protein in
      septic shock rats.
AB  - The vagus nerve and the released acetylcholine exert anti-inflammatory effects
      and inhibit septic shock. However, their detailed mechanisms remain to be
      elucidated. The present study aimed to investigate the effects of vagus nerve
      electrical stimulation on serum S100A8 levels in septic shock rats. A total of 36
      male Sprague-Dawley rats were randomly divided into six equal groups: i) Sham
      group, receiving sham operation; ii) CLP group, subjected to cecal ligation and
      puncture (CLP) to establish a model of polymicrobial sepsis; iii) VGX group,
      subjected to CLP and bilateral cervical vagotomy; iv) STM group, subjected to
      CLP, bilateral cervical vagotomy and electrical stimulation on the left vagus
      nerve trunk; v) alpha-bungarotoxin (BGT) group was administered alpha-BGT prior
      to electrical stimulation; vi) Anti-receptor for advanced glycation end products
      (RAGE) group, administered intraperitoneal injection of anti-RAGE antibody prior
      to electrical stimulation. The right carotid artery was cannulated to monitor
      mean artery pressure (MAP). The serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) levels were measured to assess the liver function.
      Serum S100A8 and advanced glycation end product (AGE) levels were measured using
      enzyme-linked immunosorbent assays. The expression of hepatic RAGE was determined
      by western blotting. The present study revealed that Sprague-Dawley rats
      exhibited progressive hypotension and significantly increased serum AST and ALT
      levels following CLP challenge compared with the sham group. The levels of S100A8
      and AGEs, and the protein expression of hepatic RAGE were significantly increased
      following CLP compared with the sham group. Vagus nerve electrical stimulation
      significantly prevented the development of CLP-induced hypotension, alleviated
      the hepatic damage, reduced serum S100A8 and AGEs production, and reduced the
      expression of hepatic RAGE. The inhibitory effect of vagus nerve electrical
      stimulation was reversed by pre-treatment with alpha-BGT and enhanced by pre
      treatment with anti-RAGE antibody. In conclusion, vagus nerve electrical
      stimulation may produce a protective effect on septic shock in rats by decreasing
      the production of S100A8. 

PMID- 27035527
TI  - Biotypes in Psychosis: Has the RDoC Era Arrived?

PMID- 27035528
TI  - A Medication for Depression With Mixed Features.

PMID- 27035529
TI  - Appetite Changes in Depression.

PMID- 27035530
TI  - Hope, Faith, Love, and Treating Serious Mental Health Conditions.

PMID- 27035531
TI  - A Case of Attenuated Psychosis Syndrome: A Broad Differential Diagnosis Requires
      Broad-Spectrum Treatment.

PMID- 27035532
TI  - Trauma and Depression in Ethiopian Women Returning From Middle Eastern Countries.

PMID- 27035533
TI  - Personalized Human Cortical Spheroids.

PMID- 27035534
TI  - Lower Dopamine D2 Receptor Expression Levels in Human Dopaminergic Neurons
      Derived From Opioid-Dependent iPSCs.

PMID- 27035535
TI  - Critical Appraisal of Existing Ketamine Trials: Existing Limitations and Limited
      Applicability for Treatment.

PMID- 27035536
TI  - Response to Zhang and Ho: Addressing Ketamine's Use in Depression.

PMID- 27035541
TI  - Differential effects of the two amino acid sensing systems, the GCN2 kinase and
      the mTOR complex 1, on primary human alloreactive CD4+ T-cells.
AB  - Amino acid deprivation activates general control nonderepressible 2 (GCN2) kinase
      and inhibits mammalian target of rapamycin (mTOR), affecting the immune response.
      In this study, the effects of GCN2 kinase activation or mTOR inhibition on human
      alloreactive CD4+ T-cells were evaluated. The mixed lymphocyte reaction, as a
      model of alloreactivity, the GCN2 kinase activator, tryptophanol (TRP), and the
      mTOR complex 1 inhibitor, rapamycin (RAP), were used. Both TRP and RAP suppressed
      cell proliferation and induced cell apoptosis. These events were p53-independent
      in the case of RAP, but were accompanied by an increase in p53 levels in the case
      of TRP. TRP decreased the levels of the Th2 signature transcription factor, GATA
      3, as RAP did, yet the latter also decreased the levels of the Th1 and Th17
      signature transcription factors, T-bet and RORgammat, whereas it increased the
      levels of the Treg signature transcription factor, FoxP3. Accordingly, TRP
      decreased the production of interleukin (IL)-4, as RAP did, but RAP also
      decreased the levels of interferon-gamma (IFN-gamma) and IL-17. Both TRP and RAP
      increased the levels of IL-10. As regards hypoxia-inducible factor-1alpha (HIF
      1alpha), which upregulates the Th17/Treg ratio, its levels were decreased by RAP.
      TRP increased the HIF-1alpha levels, which however, remained inactive. In
      conclusion, our findings indicate that, in primary human alloreactive CD4+ T
      cells, the two systems that sense amino acid deprivation affect cell
      proliferation, apoptosis and differentiation in different ways or through
      different mechanisms. Both mTOR inhibition and GCN2 kinase activation exert
      immunosuppressive effects, since they inhibit cell proliferation and induce
      apoptosis. As regards CD4+ T-cell differentiation, mTOR inhibition exerted a more
      profound effect, since it suppressed differentiation into the Th1, Th2 and Th17
      lineages, while it induced Treg differentiation. On the contrary, the activation
      of GCN2 kinase suppressed only Th2 differentiation.

PMID- 27035542
TI  - Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal
      transition and inducing apoptosis in renal cell carcinoma.
AB  - Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence,
      has been shown to have anticancer properties against several types of cancer
      cells. However, the influence of galangin on human renal cancer cells remains to
      be elucidated. In the present study, proliferation of 786-0 and Caki-1 cells was
      suppressed following exposure to various doses of galangin. Cell invasion and
      wound healing assays were used to observe the effect of galangin on invasion and
      migration. The results demonstrated that Galangin inhibited cell invasion by
      suppressing the epithelial mesenchymal transition (EMT), with an increase in the
      expression of E-cadherin and decreased expression levels of N-cadherin and
      vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The
      results revealed that galangin induced apoptosis in a dose-dependent manner. The
      accumulation of reactive oxygen species (ROS) is an important contributing factor
      for the apoptosis of various types of cancer cell. The dichlorofluorescein
      diacetate method was used to determine the level of ROS. Galangin induced the
      accumulation of intracellular ROS and malondialdehyde, and decreased the
      activities of total antioxidant and superoxide dismutase in renal cell carcinoma
      cells. Galangin exerted an antiproliferative effect and inhibited renal cell
      carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis,
      accompanied by the production of ROS. Therefore, the present data suggested that
      galangin may have beneficial effects by preventing renal cell carcinoma growth,
      inhibiting cell invasion via the EMT and inducing cell apoptosis. 

PMID- 27035543
TI  - Measles Virus Genotype D Wild Strains Suppress Interferon-Stimulated Gene
      Expression More Potently than Laboratory Strains in SiHa Cells.
AB  - Changes in interferon (IFN)-stimulated gene (ISG) expression in cells infected
      with measles virus (MeV), four wild strains (belonging to different genotypes),
      and the laboratory strain Edmonston were examined. ISGs [MxA, 2'-5'
      oligoadenylate synthetase, and interferon regulatory factor-1] were upregulated
      in an MeV-infection-induced manner and in an IFN-induced manner. In MeV-infected
      SiHa cell lines, the MeV infection-induced expression levels were in the order of
      A>H1>D8>D5>D3. On the other hand, all infected cell lines abolished type I and
      III IFN-induced ISG expression. However, partial type II IFN-mediated induction
      was observed in the MeV-infected cells. The wild strain of genotype D3 was the
      most potent inhibitor of MeV infection-induced and IFN-induced ISG expression and
      generated the highest titer of infectious viral particles. Edmonston triggered
      the highest levels of MeV infection-induced ISG expression in SiHa cells and
      produced the lowest titer of infectious particles. Expression of the viral C
      protein was associated with suppression of MeV infection-induced and type II IFN
      induced ISG expression.

PMID- 27035544
TI  - Influence of Surface Properties of Filtration-Layer Metal Oxide on Ceramic
      Membrane Fouling during Ultrafiltration of Oil/Water Emulsion.
AB  - In this work, ceramic ultrafiltration membranes deposited with different metal
      oxides (i.e., TiO2, Fe2O3, MnO2, CuO, and CeO2) of around 10 nm in thickness and
      similar roughness were tested for O/W emulsion treatment. A distinct membrane
      fouling tendency was observed, which closely correlated to the properties of the
      filtration-layer metal oxides (i.e., surface hydroxyl groups, hydrophilicity,
      surface charge, and adhesion energy for oil droplets). Consistent with the
      distinct bond strength of the surface hydroxyl groups, hydrophilicity of these
      common metal oxides is quite different. The differences in hydrophilicity
      consequently lead to different adhesion of these metal oxides toward oil
      droplets, consistent with the irreversible membrane fouling tendency. In
      addition, the surface charge of the metal oxide opposite to that of emulsion can
      help to alleviate irreversible membrane fouling in ultrafiltration. Highly
      hydrophilic Fe2O3 with the lowest fouling tendency could be a potential
      filtration-layer material for the fabrication/modification of ceramic membranes
      for O/W emulsion treatment. To the best of our knowledge, this is the first study
      clearly showing the correlations between surface properties of filtration-layer
      metal oxides and ceramic membrane fouling tendency by O/W emulsion.

PMID- 27035545
TI  - Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen
      species-mediated downregulation of the PI3K/Akt pathway.
AB  - Diallyl trisulfide (DATS) is a natural organosulfur compound isolated from
      garlic, and has been reported to possess anticancer activities. However, the
      cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma
      cells have not been well studied. The present study demonstrated that DATS
      significantly reduced cell viability in a dose- and time-dependent manner in MG63
      and MNNG/HOS cells. DATS-induced G0/G1 phase arrest was found to correlate with a
      decrease in cyclin D1 in concomitance with an increase in p21 and p27. DATS
      induced a marked increase in reactive oxygen species (ROS) levels and collapse of
      mitochondrial membrane potential (Deltapsim) in the osteosarcoma cells. DATS
      induced apoptosis in the MG63 and MNNG/HOS cells via inhibition of the PI3K/Akt
      signaling pathway and through the mitochondrial apoptotic pathway. The efficiency
      of DATS basically approached the efficacy of LY294002, a specific PI3K inhibitor.
      However, N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the
      DATS-induced ROS increase, inhibition of the PI3K/Akt pathway and cell apoptosis.
      Overall, DATS has the potential to be developed as a new anticancer drug. The
      mechanisms of action involve the ROS-mediated downregulation of the PI3K/Akt
      pathway. 

PMID- 27035546
TI  - Letter to the Editor: Endoscope-assisted hemispherotomy and corpus callostomy.

PMID- 27035547
TI  - Severe holocord syrinx in a child with megalencephaly-capillary malformation
      syndrome.
AB  - The authors present the case of a child with megalencephaly-capillary
      malformation syndrome who developed a rapidly progressive holocord syringomyelia
      that was treated surgically. A 3-year-old boy with megalencephaly-capillary
      malformation-polymicrogyria (MCAP) syndrome presented with several months of
      right leg weakness, worsening scoliosis, and increased seizures. An MRI study of
      the brain demonstrated a Chiari I malformation and massively dilated
      syringomyelia extending from C-2 to the conus medullaris. The patient underwent
      an urgent suboccipital craniectomy with C1-3 laminectomies to relieve the CSF
      outflow obstruction with significant clinical improvement. Surgery was
      complicated by bleeding from intracranial vascular malformations. This report
      describes a very rapidly developing, massive holocord syringomyelia related to
      CSF obstruction due to an unusual congenital brain malformation and associated
      vascular overgrowth at the site. Serial, premorbid MRI studies demonstrated the
      very rapid progression from no Chiari malformation, to progressively greater
      cerebellar tonsillar herniation, to holocord syrinx. This complication has never
      been reported in MCAP syndrome and should be considered in any affected MCAP
      patient with a progressive neurological decline, even if previous spine imaging
      findings were normal. Surgical complications due to hemorrhage also need to be
      considered in this vascular brain malformation. 

PMID- 27035548
TI  - Toward a better understanding of the cellular basis for cerebrospinal fluid shunt
      obstruction: report on the construction of a bank of explanted hydrocephalus
      devices.
AB  - OBJECTIVE Shunt obstruction by cells and/or tissue is the most common cause of
      shunt failure. Ventricular catheter obstruction alone accounts for more than 50%
      of shunt failures in pediatric patients. The authors sought to systematically
      collect explanted ventricular catheters from the Seattle Children's Hospital with
      a focus on elucidating the cellular mechanisms underlying obstruction. METHODS In
      the operating room, explanted hardware was placed in 4% paraformaldehyde. Weekly,
      samples were transferred to buffer solution and stored at 4 degrees C. After
      consent was obtained for their use, catheters were labeled using cell-specific
      markers for astrocytes (glial fibrillary acidic protein), microglia (ionized
      calcium-binding adapter molecule 1), and choroid plexus (transthyretin) in
      conjunction with a nuclear stain (Hoechst). Catheters were mounted in custom
      polycarbonate imaging chambers. Three-dimensional, multispectral, spinning-disk
      confocal microscopy was used to image catheter cerebrospinal fluid-intake holes
      (10* objective, 499.2-MUm-thick z-stack, 2.4-MUm step size, Olympus IX81 inverted
      microscope with motorized stage and charge-coupled device camera). Values are
      reported as the mean +/- standard error of the mean and were compared using a 2
      tailed Mann-Whitney U-test. Significance was defined at p < 0.05. RESULTS Thirty
      six ventricular catheters have been imaged to date, resulting in the following
      observations: 1) Astrocytes and microglia are the dominant cell types bound
      directly to catheter surfaces; 2) cellular binding to catheters is ubiquitous
      even if no grossly visible tissue is apparent; and 3) immunohistochemical
      techniques are of limited utility when a catheter has been exposed to Bugbee wire
      electrocautery. Statistical analysis of 24 catheters was performed, after
      excluding 7 catheters exposed to Bugbee wire cautery, 3 that were poorly fixed,
      and 2 that demonstrated pronounced autofluorescence. This analysis revealed that
      catheters with a microglia-dominant cellular response tended to be implanted for
      shorter durations (24.7 +/- 6.7 days) than those with an astrocyte-dominant
      response (1183 +/- 642 days; p = 0.027). CONCLUSIONS Ventricular catheter
      occlusion remains a significant source of shunt morbidity in the pediatric
      population, and given their ability to intimately associate with catheter
      surfaces, astrocytes and microglia appear to be critical to this pathophysiology.
      Microglia tend to be the dominant cell type on catheters implanted for less than
      2 months, while astrocytes tend to be the most prevalent cell type on catheters
      implanted for longer time courses and are noted to serve as an interface for the
      secondary attachment of ependymal cells and choroid plexus. 

PMID- 27035549
TI  - Is jugular bulb stenosis in vein of Galen aneurysmal malformation associated with
      bony remodeling of the jugular foramina?
AB  - OBJECTIVE The etiology of jugular bulb stenosis (JBS) or occlusion in the context
      of vein of Galen aneurysmal malformations (VGAMs) is unknown. It can lead to
      decompensation of a lesion that was previously clinically stable. The aim of this
      study was to describe the natural history of JBS or occlusion in VGAM and to
      determine whether there is an association with bony remodeling of the jugular
      foramina. METHODS The authors identified all cases of JBS greater than 70%
      bilaterally involving patients seen at The Hospital for Sick Children between
      January 2007 and June 2014. The foramen diameters were measured on sagittal CT
      imaging, on a slice passing at the level of the jugular vein. The jugular foramen
      diameters were also compared to measurements obtained in a matched population of
      the same age group who had no VGAM and had undergone cerebral CT for a reason
      other than vascular disease. RESULTS Eight patients (6 male and 2 female) with
      bilateral JBS were included in this series. The median duration of clinical
      follow-up was 2.5 years (IQR 1.7-4.2 years). JBS was associated with bony
      narrowing the jugular foramina in 7 of the 8 patients over time. Between 1 and 2
      years of age, patients with a VGAM demonstrated jugular foramen narrowing in
      comparison with a matched population (p = 0.015). CONCLUSIONS Jugular bulb
      stenosis or occlusion in VGAM may be associated with narrowing of the jugular
      foramina. These conditions seem to have a male predominance. If treatment is
      required, bony narrowing of the jugular foramina should be taken into account
      when deciding whether angioplasty and stent placement or surgical bypass might be
      appropriate therapeutic options. 

PMID- 27035550
TI  - Age-related carbon dioxide reactivity in children after moderate and severe
      traumatic brain injury.
AB  - OBJECTIVE The objective of this study is to assess carbon dioxide reactivity
      (CO2R) in children following traumatic brain injury (TBI). METHODS This
      prospective observational study enrolled children younger than 18 years old
      following moderate and severe TBI. Thirty-eight mechanically ventilated children
      had daily CO2R testing performed by measuring changes in their bilateral middle
      cerebral artery flow velocities using transcranial Doppler ultrasonography (TCD)
      after a transient increase in minute ventilation. The cohort was divided into 3
      age groups: younger than 2 years (n = 12); 2 to 5 years old (n = 9); and older
      than 5 years (n = 17). RESULTS Children younger than 2 years old had a lower mean
      CO2R over time. The 2-5-year-old age group had higher mean CO2R than younger
      patients (p = 0.01), and the highest CO2R values compared with either of the
      other age groups (vs > 5 years old, p = 0.046; vs < 2 years old, p = 0.002).
      Having a lower minimum CO2R had a statistically significant negative effect on
      outcome at discharge (p = 0.0413). Impaired CO2R beyond Postinjury Day 4 trended
      toward having an effect on outcome at discharge (p = 0.0855). CONCLUSIONS
      Abnormal CO2R is prevalent in children following TBI, and the degree of
      impairment varies by age. No clinical or laboratory parameters were identified as
      risk factors for impaired CO2R. Lower minimum CO2R values are associated with
      worse outcome at discharge. 

PMID- 27035551
TI  - Differential spatial regulation of BMP molecules is associated with single-suture
      craniosynostosis.
AB  - OBJECTIVE The aim of this study was to examine messenger RNA (mRNA) levels of
      bone morphogenetic protein (BMP) ligands, receptors, and soluble inhibitors in
      cells isolated from single-suture synostoses from fused coronal, metopic,
      sagittal, and lambdoid sutures. METHODS Cells were isolated from bone collected
      from patients undergoing craniotomies at Children's Healthcare of Atlanta. Real
      time polymerase chain reaction was used to examine mRNA levels in cells isolated
      from fused sutures or patent sutures in comparison with levels in normal bone
      from the same patient. RESULTS Cells isolated from fused sutures in cases of
      sagittal and coronal synostosis highly expressed BMP2, while cells isolated from
      fused metopic or lambdoid synostosis expressed high BMP4. Noggin, a BMP
      inhibitor, was lower in fused sutures and had high expression in patent sutures.
      CONCLUSIONS These results suggest that BMPs and inhibitors play a significant
      role in the regulation of suture fusion as well in the maintenance of patency in
      the normal suture. 

PMID- 27035552
TI  - Childhood hydrocephalus secondary to posterior fossa tumor is both an intra- and
      extraaxial process.
AB  - OBJECTIVE Ventricular dilation secondary to tumor obstruction of the posterior
      fossa CSF outflow in childhood is an intraaxial process. However, third
      ventriculostomy or complete tumor removal often fails to reduce the pressure in
      some children, and in others there is a delayed reduction in intracranial
      pressure; this is termed the adaptation period. The cause of this adaptation
      period has not been studied. Venous sinus compression is highly correlated with
      other forms of childhood hydrocephalus, and this study seeks to follow the
      changes that occur in sinus cross-sectional area after surgery. METHODS Twelve
      children with posterior fossa tumors underwent MRI examination that included
      standard T2-weighted and 3D contrast-enhanced images obtained preoperatively, in
      the immediate postoperative period, and after several months. The volumes of the
      lateral and third ventricles and the minimum cross-sectional area of the
      transverse and sigmoid sinuses were measured. Patients were categorized by 1)
      shunt status (those who required a shunt vs those who did not) and 2) by age
      (those younger than 3 years vs those older than 3 years at diagnosis). RESULTS
      There was a significant reduction in ventricular volume in both the immediate and
      secondary follow-up periods for all patients. There was preoperative venous sinus
      compression in all groups, which did not change significantly in the immediate
      postoperative period but did improve in the secondary follow-up period. The
      younger children had larger ventricles and smaller sinuses before surgery
      compared with the older children. CONCLUSIONS In children with obstructed
      hydrocephalus caused by tumor, there is secondary compression of venous outflow,
      indicating both an intra- and extraaxial process. The expansion of the sinuses
      following decompression of the posterior fossa is delayed and may correlate with
      the adaptation period. Younger children have greater sinus compression than older
      ones. 

PMID- 27035553
TI  - Enhanced tumor retention of radioiodinated anti-epidermal growth factor receptor
      antibody using novel bifunctional iodination linker for radioimmunotherapy.
AB  - Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver
      cytotoxic radiation to a target tumor cells. Radioiodine is most commonly
      employed to prepare radiolabeled proteins (antibodies, peptides) for in vitro and
      in vivo applications. A major shortcoming of radioiodinated proteins prepared by
      direct labeling methods is their deiodination in vivo. For the preparation of
      more stable radioiodinated antibodies, we developed a new linker (N-(4
      isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA). This study
      evaluated the usefulness of IBPA as a linker for the stable radioiodinated
      internalizing antibody, cetuximab. Directly labeled cetuximab ([125I]-cetuximab)
      was prepared by the chloramine T method. To prepare indirectly labeled cetuximab
      using IBPA ([125I]-IBPA-cetuximab), IBPA was radioiodinated using chloramine-T to
      give N-(4-isothiocyanatobenzyl)-2-(3-[125I]phenyl)acetamide ([125I]-IBPA), which
      was purified by high performance liquid chromatography. [125I]-IBPA was then
      conjugated to cetuximab. In vitro target binding and internalizing assays were
      performed in PC9, LS174T, and FaDu cell lines. In vivo planar images were
      obtained using an Inveon SPECT scanner 3, 24, 48, and 168 h after i.v. injection
      of [125I]-cetuximab or [125I]-IBPA-cetuximab in athymic mice bearing LS174T tumor
      xenografts. Specific binding and internalized radioactivity of [125I]-IBPA
      cetuximab were higher than those of [125I]-cetuximab in PC9, LS174T, and FaDu
      cell lines. In planar images scant radioactivity was evident in thyroid glands
      after injection of [125I]-IBPA-cetuximab, while a high level of radioactivity was
      present in thyroid glands after injection of [125I]-cetuximab. Tumor uptake value
      of [125I]-IBPA-cetuximab was higher than that of [125I]-cetuximab for up to 168
      h. [125I]-IBPA-cetuximab is stable and resistant to deiodination in vivo. IBPA is
      a promising bi-functional linker for radioiodination of internalizing monoclonal
      antibodies for in vivo applications including radioimmunotherapy. 

PMID- 27035554
TI  - miR-140-5p regulates angiogenesis following ischemic stroke by targeting VEGFA.
AB  - MicroRNA (miRNA or miR) expression profiles are altered in tissues under hypoxic
      ischemic conditions. The expression of miR-140 is downregulated >2-fold following
      hypoxic-ischemic brain damage, however, its role in angiogenesis subsequent to
      cerebral ischemia is not fully understood. The present study aimed to investigate
      the role of miR-140-5p in angiogenesis and the molecular mechanism mediated by
      vascular endothelial growth factor A (VEGFA) in an in vitro model for brain
      ischemia. A rat middle cerebral artery occlusion (MCAO) model was constructed,
      and the results from reverse transcription-quantitative polymerase chain reaction
      and western blot analysis demonstrated that the expression levels of miR-140-5p
      were significantly decreased, while the expression levels of VEGFA were
      significantly increased between 12 and 48 h in the rat cerebral following MCAO.
      Furthermore, human umbilical vein endothelial cells (HUVECs) were exposed to low
      oxygen conditions and it was demonstrated that hypoxia downregulated miR-140-5p
      and upregulated VEGFA expression levels. The miR-140-5p mimic was transfected
      into the normoxic and hypoxic HUVECs and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide, Transwell migration and tube formation assays were
      performed. The results indicated that miR-140-5p inhibited angiogenesis by
      decreasing cell proliferation, migration and tube formation. Additionally, in
      human embryonic kidney 293 cells, results from the luciferase reporter assay
      revealed that miR-140-5p directly targeted the 3' untranslated region of VEGFA
      and that miR-140-5p regulated the protein expression of VEGFA. To further analyze
      this effect, a VEGFA-pEGFP-C1 plasmid was transfected into the normoxic and
      hypoxic HUVECs, and it was revealed that the inhibitory effect of miR-140-5p on
      angiogenesis was attenuated by the overexpression of VEGFA. In conclusion, to the
      best of our knowledge, the present study is the first to suggest that miR-140-5p
      exerts an inhibitory effect on angiogenesis in an in vitro model of ischemia, and
      this effect is achieved partially by targeting VEGFA. The present study provided
      a novel biomarker for the treatment of cerebral ischemia. 

PMID- 27035555
TI  - MicroRNA-21 modulates radiation resistance through upregulation of hypoxia
      inducible factor-1alpha-promoted glycolysis in non-small cell lung cancer cells.
AB  - Aberrant microRNA (miRNA) expression in cancer affects the transcription of
      target genes, and profoundly influences cancer-associated signaling pathways.
      Radiation resistance is a major problem encountered in the treatment of cancer.
      The present study aimed to investigate the role of miRNA (miR)-21 in the
      development of radiation resistance in non-small cell lung cancer cells. A
      radiation-resistant cell line was generated from A549 cells. Significant
      upregulation of miR-21 was detected in the radioresistant cancer cells, as
      compared with the radiosensitive cells, and overexpression of miR-21 rendered
      A549 parental cells resistant to radiation. In addition, glycolysis was increased
      in the radioresistant cells, as compared with the sensitive cells. Furthermore,
      hypoxia-inducible factor-1alpha (HIF1alpha) was upregulated by miR-21 in
      radioresistant cells, resulting in promotion of the key enzymes of glycolysis.
      Inhibition of HIF1alpha by small interfering RNA suppressed glycolysis and
      resensitized the cancer cells to radiation, whereas the recovery of HIF1alpha in
      miR-21-inhibited radioresistant cells resulted in recovery of radioresistance. In
      conclusion, the present study suggested that miR-21 may modulate radioresistance
      through the upregulation of HIF1alpha. These results may provide a novel
      perspective on miRNA for the development of anti-radioresistance drugs. 

PMID- 27035556
TI  - Haliclonadiamine Derivatives and 6-epi-Monanchorin from the Marine Sponge
      Halichondria panicea Collected at Iriomote Island.
AB  - Four new haliclonadiamine analogues, (10Z,12E)-haliclonadiamine (1), (10E,12Z)
      haliclonadiamine (2), and halichondriamines A (3) and B (4), were isolated from
      the Okinawan marine sponge Halichondria panicea together with haliclonadiamine
      (5) and papuamine (6). The structures of 1-4 were elucidated on the basis of
      their spectroscopic data by comparisons with those for 5 and 6. Further
      separation of the remaining fraction led to the isolation of a new bicyclic
      guanidine alkaloid, 6-epi-monanchorin (7), along with monanchorin (8). Compound 7
      is the epimer of 8 at the 6 position. Compounds 1-6 inhibited the growth of
      Mycobacterium smegmatis with inhibition zones of 12, 7, 8, 7, 16, and 12 mm at 10
      MUg/disc, respectively. Compounds 2-4 exhibited weak cytotoxicities against the
      Huh-7 (hepatoma) human cancer cell line and were 2-fold less active than 5 and 6.
      Compounds 7 and 8 were not active against M. smegmatis at 20 MUg/disc or the
      cancer cell line at 10 MUM.

PMID- 27035558
TI  - Role of estrogen receptor in breast cancer cell gene expression.
AB  - The aim of the present study was to establish the underlying regulatory mechanism
      of estrogen receptor (ER) in breast cancer cell gene expression. A gene
      expression profile (accession no. GSE11324) was downloaded from the Gene
      Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from an
      estrogen treatment group and a control group were identified. Chromatin
      immunoprecipitation with high-throughput sequencing data (series GSE25710) was
      obtained from the GEO for the ER binding sites, and binding and expression target
      analysis was performed. A total of 3,122 DEGs were obtained and ER was
      demonstrated to exhibit inhibition and activation roles during the regulation of
      its target gene expression. Motif analysis revealed that the upregulated target
      genes that demonstrated interactions with ER were meis homeobox 1 (MEIS1) and
      forkhead box P3 (FOXP3). The downregulated target genes, which demonstrated
      interactions with ER, were thyroid hormone receptor, beta (THRB) and grainyhead
      like 1 (GRHL1). Thus, it was observed that ER stimulated gene expression by
      interacting with MEIS1 and FOXP3, and ER inhibited gene expression by interacting
      with THRB and GRHL1. However, additional experiments are required to provide
      further confirmation of these findings. 

PMID- 27035559
TI  - A comparative study of the timecourse of the expression of the thermo-inducible
      HSP70 gene in clinical and environmental isolates of Aspergillus fumigatus.
AB  - The internal environment within animals or humans provides different conditions
      to invading saprophytic fungal pathogens, requiring the differential regulation
      of genes in comparison to environmental conditions. Understanding the mechanisms
      by which pathogens regulate genes within the host may be key in determining
      pathogen behavior within the host and may additionally facilitate further
      investigation into novel therapeutic agents. The heat shock protein (HSP)70 gene
      and its associated proteins have been frequently reported to be among the most
      highly expressed and dominant proteins present within various locations at
      physiological temperatures. The present study examined relative gene expression
      levels of the HSP70 gene in Aspergillus fumigatus isolates from both clinical and
      environmental origins, at a range of temperature points (20, 30, 37 and 42C) over
      five days, using reverse transcription-quantitative polymerase chain reaction,
      comparing with a standard A. fumigatus strain incubated at 25C. The results
      indicated a differential gene expression pattern for the environmental and
      clinical isolates. During the five days, the HSP70 expression levels in the
      clinical samples were higher than in the environmental samples. However, the
      difference in the expression levels between the two groups at 42C was reduced.
      The mean HSP70 expression level over the five incubation days demonstrated a
      gradual and continual increasing trend by temperature elevation in both groups at
      30, 37 and 42C, however, at 20C both groups demonstrated reduced expression. The
      temperature shift from 20 to 42C resulted in HSP70 induction and up to a 10- and
      8.6-fold change in HSP70 expression levels on the fifth day of incubation in the
      clinical and environmental groups, respectively. In conclusion, incubation at 37
      and 42C resulted in the highest expression levels in both experimental groups,
      with these temperature points important for the induction of HSP70 expression in
      A. fumigatus. 

PMID- 27035560
TI  - Identification of prognostic microRNA candidates for head and neck squamous cell
      carcinoma.
AB  - The aim of the present study was to uncover potential prognostic microRNA (miRNA)
      markers in head and neck squamous cell carcinoma (HNSCC). miRNA expression
      profile and clinical data were obtained from The Cancer Genome Atlas (TCGA)
      database. Survival analysis was conducted by Kaplan-Meier method. Then, candidate
      prognostic miRNAs were screened via Cox proportional hazards regression analysis.
      Furthermore, target genes of miRNAs were predicted, and their interactions and
      functions were then analyzed. A total of 15 miRNAs were discovered to be
      significantly related to overall survival. Among them, miR-1251, miR-618 and miR
      328 with p<0.05 were potentially significant prognostic factors of HNSCC. In the
      protein-protein interaction (PPI) network, the target gene of miR-328, MAX,
      interacted with multiple genes. The target gene of miR-618, E2F1, interacted with
      genes such as MAX, SMAD3 and IGF1. Furthermore, the target genes of miR-618 (e.g.
      E2F1 and SMAD3), and the target genes of miR-328 (e.g. MAX) were significantly
      enriched in the functions of transcriptional regulation. The target gene of miR
      1251, IGF1, was associated with functions such as signal transduction. The above
      miRNAs (miR-1251, miR-618 and miR-328) may be potential prognostic markers in
      HNSCC. 

PMID- 27035561
TI  - Studies on the purification of polysaccharides separated from Tremella fuciformis
      and their neuroprotective effect.
AB  - The present study aimed to investigate the protective effect of purified
      polysaccharides from Tremella fuciformis against glutamate-induced cytotoxicity
      in differentiated PC12 (DPC12) cells. The aqueous extract of Tremella fuciformis
      was purified using a DEAE-52 cellulose anion exchange column and a Sepharose G
      100 column, respectively. A fraction termed TL04 with a 2,033 kDa molecular
      weight was obtained. The backbone of TL04 is composed of (1->2)- and (1->4)
      linked-mannose and (1->3)-linked-glucans. Results revealed that TL04 treatment
      improved cell viability and suppressed reactive oxygen species accumulation,
      lactose dehydrogenase release and caspase-3 activity, and ameliorated
      mitochondrial abnormal alteration caused by glutamate. TL04 pretreatment enhanced
      the level of B-cell lymphoma 2 (Bcl-2), and suppressed Bax expression and
      cytochrome c (Cyto C) release in glutamate-treated cells. Exposure to glutamate
      strongly increased the activity of caspase-8, caspase-9 and caspase-3, which were
      significantly reversed by TL04 pretreatment. The presence of Ac-DEVD-CHO (a
      caspase-3 inhibitor) markedly enhanced the potency of TL04 in improving the
      viability of glutamate-exposed DPC12 cells. Collectively, the results
      demonstrated that the purified polysaccharides separated from Tremella fuciformis
      (TL04) possess a neuroprotective effect against glutamate-induced DPC12 cell
      damage predominantly through the caspase-dependent mitochondrial pathway. The
      present study provides an experimental foundation supporting purified TL04 as a
      potential therapeutic agent for neurodegenerative diseases. 

PMID- 27035557
TI  - Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2
      Diabetes.
AB  - To date, more than 30 genes have been linked to monogenic diabetes. Candidate
      gene and genome-wide association studies have identified > 50 susceptibility loci
      for common type 1 diabetes (T1D) and approximately 100 susceptibility loci for
      type 2 diabetes (T2D). About 1-5% of all cases of diabetes result from single
      gene mutations and are called monogenic diabetes. Here, we review the
      pathophysiological basis of the role of monogenic diabetes genes that have also
      been found to be associated with common T1D and/or T2D. Variants of approximately
      one-third of monogenic diabetes genes are associated with T2D, but not T1D. Two
      of the T2D-associated monogenic diabetes genes-potassium inward-rectifying
      channel, subfamily J, member 11 (KCNJ11), which controls glucose-stimulated
      insulin secretion in the beta-cell; and peroxisome proliferator-activated
      receptor gamma (PPARG), which impacts multiple tissue targets in relation to
      inflammation and insulin sensitivity-have been developed as major antidiabetic
      drug targets. Another monogenic diabetes gene, the preproinsulin gene (INS), is
      unique in that INS mutations can cause hyperinsulinemia, hyperproinsulinemia,
      neonatal diabetes mellitus, one type of maturity-onset diabetes of the young
      (MODY10), and autoantibody-negative T1D. Dominant heterozygous INS mutations are
      the second most common cause of permanent neonatal diabetes. Moreover, INS gene
      variants are strongly associated with common T1D (type 1a), but inconsistently
      with T2D. Variants of the monogenic diabetes gene Gli-similar 3 (GLIS3) are
      associated with both T1D and T2D. GLIS3 is a key transcription factor in insulin
      production and beta-cell differentiation during embryonic development, which
      perturbation forms the basis of monogenic diabetes as well as its association
      with T1D. GLIS3 is also required for compensatory beta-cell proliferation in
      adults; impairment of this function predisposes to T2D. Thus, monogenic forms of
      diabetes are invaluable "human models" that have contributed to our understanding
      of the pathophysiological basis of common T1D and T2D.

PMID- 27035562
TI  - NAMPT protects against 6-hydroxydopamine-induced neurotoxicity in PC12 cells
      through modulating SIRT1 activity.
AB  - Parkinson's disease (PD) is the second most common progressive neurodegenerative
      movement disorder. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the
      first rate-limiting step in the nicotinamide adenine dinucleotide (NAD+)
      biosynthetic pathway in mammals, is a substrate for NAD+-dependent enzymes, such
      as sirtuin 1 (SIRT1), and contributes to cell fate decisions. However, the role
      of NAMPT in PD has remained to be fully elucidated. In the present study, PC12
      cells were treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to establish an
      in vitro model of PD, following which an obvious inhibitory effect on the levels
      of NAMPT and NAD+ as well as the NAD+/NADH ratio was detected. In addition, pre
      incubation with FK866, a highly specific NAMPT inhibitor, enhanced the inhibitory
      effects of 6-OHDA on the viability of PC12, while pre-incubation with
      nicotinamide mononucleotide (NMN), am enzymatic product of NAMPT, had the
      opposite effect. Furthermore, it was revealed that NMN markedly attenuated 6-OHDA
      induced decreases in superoxide dismutase activity and glutathione levels, as
      well as 6-OHDA-induced increases in malondialdehyde and lactate dehydrogenase in
      PC12 cells. Furthermore, 6-OHDA significantly reduced SIRT1 activity in PC12
      cells, which was inhibited by NMN. The pharmacological activator resveratrol also
      significantly inhibited 6-OHDA-mediated decreases in PC12 cell viability while
      reversing 6-OHDA-induced decreases in SIRT1 levels. The results of the present
      study suggested that NMT protected against 6-OHDA-induced decreases in PC12 cell
      viability, and that SIRT1 activation had a role in this process. Treatment with
      NMN to activate SIRT1 may represent a novel therapeutic strategy for treating PD.

PMID- 27035563
TI  - EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M
      arrest through downregulation of Cyclin B1/CDK1 signaling.
AB  - There are no effective therapies for advanced renal cell carcinoma (RCC), except
      for VEGFR inhibitors with only ~50% response rate. To identify novel targets and
      biomarkers for RCC is of great importance in treating RCC. In this study, we
      observed that eukaryotic initiation factor 3d (EIF3D) expression was
      significantly increased in RCC compared with paracarcinoma tissue using
      immunohistochemistry staining and western blot analysis. Furthermore,
      bioinformatics meta-analysis using ONCOMINE microarray datasets showed that EIF3D
      mRNA expressions in CCRCC tissue specimens were significantly higher than that in
      normal tissue specimens. In addition, RCC tissue microarray demonstrated that
      elevated EIF3D expression was positively correlated with TNM stage and tumor
      size. EIF3D silencing in human 786-O and ACHN CCRCC cell lines by RNA
      interference demonstrated that EIF3D knockdown obviously inhibited cell
      proliferation and colony formation, caused G2/M arrest through downregulation of
      Cyclin B1 and Cdk1 and upregulation of p21, and induced apoptosis shown by sub-G1
      accumulation and RARP cleavage. Moreover, correlation analysis using ONCOMINE
      microarray datasets indicated that increased EIF3D mRNA expression was positively
      correlated to PCNA, Cyclin B1 and CDK1 mRNA expression in RCC. Collectively,
      these results provide reasonable evidences that EIF3D may function as a potential
      proto-oncogene that participates in the occurrence and progression of RCC. 

PMID- 27035564
TI  - mir-1-mediated paracrine effect of cancer-associated fibroblasts on lung cancer
      cell proliferation and chemoresistance.
AB  - Lung cancer is the leading cause of cancer-related mortality in humans worldwide.
      Moreover, the overall 5-year survival rate is only 15%. Pathologically almost 80%
      of all lung cancer cases are non-small cell lung cancer (NSCLC). Cancer
      associated fibroblasts (CAFs) have been found to exist in a large number of
      NSCLCs. CAFs have been proven to promote tumor progression, metastasis and
      resistance to therapy through paracrine effects in most solid tumors. In the
      present study, firstly we isolated CAFs from patient tissues and demonstrated
      that they promoted cell proliferation and chemoresistance to cisplatin in the
      lung cancer cell lines A549 and 95D in a paracrine manner. Secondly, using ELISA
      and quantative PCR, we found that a higher amount of stromal cell-derived factor
      1 (SDF-1) existed in the CAFs rather than that observed in the normal fibroblasts
      (NFs). Thirdly, we detected that SDF-1 facilitated lung cancer cell proliferation
      and drug resistance via the CXCR4-mediated signaling pathway which involved NF
      kappaB and Bcl-xL. Moreover, we also confirmed that the expression level of SDF-1
      in the CAFs was negatively regulated by microRNA mir-1 through microRNA
      overexpression and quantitative PCR. Overall, our data provide one explanation
      for the effects of CAFs on lung cancer cells. Meanwhile, our results also suggest
      CAFs as a potential therapeutic target in tumor treatment. 

PMID- 27035565
TI  - Inhibitory effect of Zanthoxylum bungeanum seed oil on ovalbumin-induced lung
      inflammation in a murine model of asthma.
AB  - The present study aimed to investigate the therapeutic efficacy of Zanthoxylum
      bungeanum seed oil (Z. seed oil) to alleviate airway inflammation in asthmatic
      mice. The asthmatic mice were treated with vehicle, ovalbumin (OVA), or OVA + Z.
      seed oil (2 g/kg) for between 24 h and 14 days. Following treatment, inflammatory
      cell infiltration and pulmonary tissue damage were assessed by hematoxylin and
      eosin staining, and immunohistochemistry. The expression levels of pro
      inflammatory cytokines, chemokines, adhesion molecules and mitogen activated
      protein kinase signaling proteins were measured by enzyme-linked immunosorbent
      assays, reverse transcription quantitative-polymerase chain reaction and western
      blot analysis. In asthmatic mice, administration of Z. seed oil attenuated lung
      tissue injury and airway remodeling, and inhibited the infiltration of leukocytes
      and eosinophils into the airway by reducing the expression levels of inflammatory
      cytokines and chemokines compared with OVA-treated mice (P<0.05). Z. seed oil
      also reduced the levels of inflammatory chemokine and adhesion molecules via
      downregulation of extracellular signal-regulated kinase and activation of c-JUN N
      terminal kinase in the Z. seed-treated mice compared with OVA-treated mice
      (P<0.05). Thus, data from the present study indicates that Z. seed oil can
      suppress pulmonary inflammation and tissue injury during asthma, and suggests
      that it may be used to effectively treat allergen-induced asthma. 

PMID- 27035566
TI  - Knockdown of SCARA5 inhibits PDGF-BB-induced vascular smooth muscle cell
      proliferation and migration through suppression of the PDGF signaling pathway.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration are critical in
      the progression of atherosclerosis and can be induced by platelet-derived growth
      factor (PDGF). Several studies have demonstrated that scavenger receptor class A,
      member 5 (SCARA5) is important in cancer cell migration and invasion. However,
      the role of SCARA5 in VSMCs remains to be elucidated in the development of
      atherosclerosis. Therefore, the role of SCARA5 was investigated in PDGF-BB
      stimulated VSMC proliferation and migration. In the present study, it was shown
      that SCARA5 expression was enhanced by PDGF-BB in human aortic smooth muscle
      cells (HASMCs). Knockdown of SCARA5 by small interfering (si)RNA significantly
      inhibited PDGF-BB-induced HASMC proliferation and migration. Furthermore, siRNA
      SCARA5 significantly inhibited the phosphorylation of PDGF receptor (PDGFR) beta,
      AKT and extracellular signal-regulated kinase 1/2 in PDGF-BB-stimulated HASMCs.
      In conclusion, this study demonstrated that knockdown of SCARA5 inhibits PDGF-BB
      induced HASMC proliferation and migration through suppression of the PDGF
      signaling pathway. Thus, SCARA5 may be a novel therapeutic target for preventing
      or treating vascular diseases involving VSMC proliferation and migration. 

PMID- 27035567
TI  - Screening for Atrial Fibrillation--A Cross-Sectional Survey of Healthcare
      Professionals in Primary Care.
AB  - INTRODUCTION: Screening for atrial fibrillation (AF) in primary care has been
      recommended; however, the views of healthcare professionals (HCPs) are not known.
      This study aimed to determine the opinions of HCP about the feasibility of
      implementing screening within a primary care setting. METHODS: A cross-sectional
      mixed methods census survey of 418 HCPs from 59 inner-city practices (Nottingham,
      UK) was conducted between October-December 2014. Postal and web-surveys
      ascertained data on existing methods, knowledge, skills, attitudes, barriers and
      facilitators to AF screening using Likert scale and open-ended questions.
      Responses, categorized according to HCP group, were summarized using proportions,
      adjusting for clustering by practice, with 95% C.Is and free-text responses using
      thematic analysis. RESULTS: At least one General Practitioner (GP) responded from
      48 (81%) practices. There were 212/418 (51%) respondents; 118/229 GPs, 67/129
      nurses [50 practice nurses; 17 Nurse Practitioners (NPs)], 27/60 healthcare
      assistants (HCAs). 39/48 (81%) practices had an ECG machine and diagnosed AF in
      house. Non-GP HCPs reported having less knowledge about ECG interpretation,
      diagnosing and treating AF than GPs. A greater proportion of non-GP HCPs reported
      they would benefit from ECG training specifically for AF diagnosis than GPs
      [proportion (95% CI) GPs: 11.9% (6.8-20.0); HCAs: 37.0% (21.7-55.5); nurses:
      44.0% (30.0-59.0); NPs 41.2% (21.9-63.7)]. Barriers included time, workload and
      capacity to undertake screening activities, although training to diagnose and
      manage AF was a required facilitator. CONCLUSION: Inner-city general practices
      were found to have adequate access to resources for AF screening. There is
      enthusiasm by non-GP HCPs to up-skill in the diagnosis and management of AF and
      they may have a role in future AF screening. However, organisational barriers,
      such as lack of time, staff and capacity, should be overcome for AF screening to
      be feasibly implemented within primary care.

PMID- 27035568
TI  - [Neoadjuvant Radiochemotherapy Followed by Curative Resection in Patients with
      Advanced Non-Small Cell Lung Cancer in Stage IIIA/IIIB: Prognostic Factors and
      Results].
AB  - The role of surgical lung resection following neo-adjuvant radio-chemotherapy
      (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet
      not clearly defined. The aim of our study was to analyze the postoperative
      survival and to identify relevant prognostic factors. 46 patients underwent
      curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB)
      between February 2008 and February 2015. A retrospective data analysis regarding
      preoperative regression status, perioperative mortality, postoperative survival,
      patho-histological remission, relapse pattern and other prognostic factors was
      performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45-60]
      Gy was performed in 44 (96 %) patients. Partial and/or complete regression was
      observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients.
      The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The
      overall and progression free 5-year survival rate was 47 % and respectively 45 %
      [in median 58 months]. The 5-year survival rate of 64 % in the "responder"-group
      was significantly better when compared with 24 % in the "non-responder"-group (p
      = 0.038). The tri-modality therapy improved the prognosis in patients with
      locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological
      remission is an important prognostic factor for better long term survival.
      Dividing the patients in "responder" and "non-responder" after neo-adjuvant RCT
      may have large therapeutically consequences in the future. 

PMID- 27035569
TI  - Do People Agree on What Makes One Feel Loved? A Cognitive Psychometric Approach
      to the Consensus on Felt Love.
AB  - This pragmatic study examines love as a mode of communication. Our focus is on
      the receiver side: what makes an individual feel loved and how felt love is
      defined through daily interactions. Our aim is to explore everyday life scenarios
      in which people might experience love, and to consider people's converging and
      diverging judgments about which scenarios indicate felt love. We apply a
      cognitive psychometric approach to quantify a receiver's ability to detect,
      understand, and know that they are loved. Through crowd-sourcing, we surveyed lay
      participants about whether various scenarios were indicators of felt love. We
      thus quantify these responses to make inference about consensus judgments of felt
      love, measure individual levels of agreement with consensus, and assess
      individual response styles. More specifically, we (1) derive consensus judgments
      on felt love; (2) describe its characteristics in qualitative and quantitative
      terms, (3) explore individual differences in both (a) participant agreement with
      consensus, and (b) participant judgment when uncertain about shared knowledge,
      and (4) test whether individual differences can be meaningfully linked to
      explanatory variables. Results indicate that people converge towards a shared
      cognitive model of felt love. Conversely, respondents showed heterogeneity in
      knowledge of consensus, and in dealing with uncertainty. We found that, when
      facing uncertainty, female respondents and people in relationships more
      frequently judge scenarios as indicators of felt love. Moreover, respondents from
      smaller households tend to know more about consensus judgments of felt love,
      while respondents from larger households are more willing to guess when unsure of
      consensus. 

PMID- 27035570
TI  - Design Principles of Pancreatic Islets: Glucose-Dependent Coordination of Hormone
      Pulses.
AB  - Pancreatic islets are functional units involved in glucose homeostasis. The
      multicellular system comprises three main cell types; beta and alpha cells
      reciprocally decrease and increase blood glucose by producing insulin and
      glucagon pulses, while the role of delta cells is less clear. Although their
      spatial organization and the paracrine/autocrine interactions between them have
      been extensively studied, the functional implications of the design principles
      are still lacking. In this study, we formulated a mathematical model that
      integrates the pulsatility of hormone secretion and the interactions and
      organization of islet cells and examined the effects of different cellular
      compositions and organizations in mouse and human islets. A common feature of
      both species was that islet cells produced synchronous hormone pulses under low-
      and high-glucose conditions, while they produced asynchronous hormone pulses
      under normal glucose conditions. However, the synchronous coordination of insulin
      and glucagon pulses at low glucose was more pronounced in human islets that had
      more alpha cells. When beta cells were selectively removed to mimic diabetic
      conditions, the anti-synchronicity of insulin and glucagon pulses was
      deteriorated at high glucose, but it could be partially recovered when the re
      aggregation of remaining cells was considered. Finally, the third cell type,
      delta cells, which introduced additional complexity in the multicellular system,
      prevented the excessive synchronization of hormone pulses. Our computational
      study suggests that controllable synchronization is a design principle of
      pancreatic islets. 

PMID- 27035571
TI  - Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of
      Parkinson's Disease Stages?
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) can be used to identify biomarkers
      in Parkinson's disease (PD); R2* values reflect iron content related to high
      levels of oxidative stress, whereas volume and/or shape changes reflect neuronal
      death. We sought to assess iron overload in the nigrostriatal system and
      characterize its relationship with focal and overall atrophy of the striatum in
      the pivotal stages of PD. METHODS: Twenty controls and 70 PD patients at
      different disease stages (untreated de novo patients, treated early-stage
      patients and advanced-stage patients with L-dopa-related motor complications)
      were included in the study. We determined the R2* values in the substantia nigra,
      putamen and caudate nucleus, together with striatal volume and shape analysis. We
      also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up
      two years later in the early-stage PD patients. RESULTS: The R2* values in the
      substantia nigra, putamen and caudate nucleus were significantly higher in de
      novo PD patients than in controls. Early-stage patients displayed significantly
      higher R2* values in the substantia nigra (with changes in striatal shape),
      relative to de novo patients. Measurements after a two-year follow-up in early
      stage patients and characterization of the acute MPTP mouse model confirmed that
      R2* changed rapidly with disease progression. Advanced-stage patients displayed
      significant atrophy of striatum, relative to earlier disease stages. CONCLUSION:
      Each pivotal stage in PD appears to be characterized by putative nigrostriatal
      MRI biomarkers: iron overload at the de novo stage, striatal shape changes at
      early-stage disease and generalized striatal atrophy at advanced disease.

PMID- 27035572
TI  - Outbreak of influenza-like illness investigated during August 2013 near Indo
      China border of Arunachal Pradesh, Northeast India.
AB  - During August 2013, an outbreak of influenza-like illnesses (ILI) was
      investigated in Monigong area, near Indo-China border of Arunachal Pradesh,
      Northeast India. Influenza type A/H3N2 was detected by RT-PCR in 33.3% (8/24) of
      ILI cases. Sequence analysis of HA and NA genes revealed eight and five amino
      acid substitutions, respectively in Monigong H3N2 (Mo/H3N2) strains as compared
      to vaccine strain A/Victoria/361/2011. Four non-synonymous substitutions, three
      localizing at antigenic sites T144A, A; R158G, B; L173S, D, and one H9Y in close
      proximity to a potential glycosylation site aa8 in HA1 domain along with the
      substitution T329N in NA are likely to influence the antigenicity/virulence of
      Mo/H3N2 viruses. J. Med. Virol. 88:1999-2003, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27035573
TI  - Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect
      Macrophages.
AB  - BACKGROUND: During Trypanosoma cruzi infection, macrophages produce reactive
      oxygen species (ROS) in a process called respiratory burst. Several works have
      aimed to elucidate the role of ROS during T. cruzi infection and the results
      obtained are sometimes contradictory. T. cruzi has a highly efficiently regulated
      antioxidant machinery to deal with the oxidative burst, but the parasite
      macromolecules, particularly DNA, may still suffer oxidative damage. Guanine (G)
      is the most vulnerable base and its oxidation results in formation of 8-oxoG, a
      cellular marker of oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: In order to
      investigate the contribution of ROS in T. cruzi survival and infection, we
      utilized mice deficient in the gp91phox (Phox KO) subunit of NADPH oxidase and
      parasites that overexpress the enzyme EcMutT (from Escherichia coli) or TcMTH
      (from T. cruzi), which is responsible for removing 8-oxo-dGTP from the nucleotide
      pool. The modified parasites presented enhanced replication inside murine
      inflammatory macrophages from C57BL/6 WT mice when compared with control
      parasites. Interestingly, when Phox KO macrophages were infected with these
      parasites, we observed a decreased number of all parasites when compared with
      macrophages from C57BL/6 WT. Scavengers for ROS also decreased parasite growth in
      WT macrophages. In addition, treatment of macrophages or parasites with hydrogen
      peroxide increased parasite replication in Phox KO mice and in vivo. CONCLUSIONS:
      Our results indicate a paradoxical role for ROS since modified parasites multiply
      better inside macrophages, but proliferation is significantly reduced when ROS is
      removed from the host cell. Our findings suggest that ROS can work like a
      signaling molecule, contributing to T. cruzi growth inside the cells.

PMID- 27035574
TI  - Secondary Solid Organ Neoplasm in Patients with Acute Lymphoblastic Leukemia: A
      Nationwide Population-Based Study in Taiwan.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is more common in children than in
      adults. Secondary neoplasms (SNs) in childhood ALL have been widely reported.
      However, only one study has demonstrated SNs in adult ALL. Because of the poorer
      survival of adult ALL, the incidence might be underestimated. OBJECTIVE: To
      evaluate the incidence and risk factors of secondary solid organ neoplasms among
      adult and child ALL patients. METHODS: Newly diagnosed ALL patients between 1997
      and 2011 were recruited from the Taiwan National Health Insurance database. Those
      who had antecedent or combined malignancies were excluded. Standardized incidence
      ratios (SIRs) were analyzed to compare the risk of our cohort to general
      population in the same age, sex and calendar year. Risk factors for SN
      development were analyzed by Cox proportional hazards models. Effects of
      treatments were treated as time-dependent variables. RESULTS: The 15-year
      cumulative incidence of SN was 1.9% and 8.4% in 1,381 child and 2,154 adult ALL
      patients, respectively. The SIR was significantly increased in child ALL (SIR
      6.06), but not in adult ALL (SIR 1.16). The SIRs of follow-up periods were 5.14,
      2.24, .87 and .71 at >= 10 years, 5-10 years, 1-5 years and 0-1, respectively.
      Overall, 15 SNs developed, and CNS tumors (SIR 11.56) were the most common type.
      Multivariate analysis showed that age >= 20 years (hazard ratio [HR] 5.04), end
      stage renal disease (HR 18.98) and cranial irradiation (HR 8.12) were independent
      risk factors for cancer development. CONCLUSIONS: When compared with the general
      population, child ALL shows a increased risk of developing SNs. CNS tumors are
      the most common type, and cranial irradiation is an independent risk factor. With
      longer follow-up, the risk of SNs increases. Hence, physicians need to pay more
      attention on the risk of developing SNs in long-term ALL survivors with risk
      factors.

PMID- 27035575
TI  - Photovoltaic Grid-Connected Modeling and Characterization Based on Experimental
      Results.
AB  - A grid-connected photovoltaic (PV) system operates under fluctuated weather
      condition has been modeled and characterized based on specific test bed. A
      mathematical model of a small-scale PV system has been developed mainly for
      residential usage, and the potential results have been simulated. The proposed PV
      model based on three PV parameters, which are the photocurrent, IL, the reverse
      diode saturation current, Io, the ideality factor of diode, n. Accuracy of the
      proposed model and its parameters evaluated based on different benchmarks. The
      results showed that the proposed model fitting the experimental results with high
      accuracy compare to the other models, as well as the I-V characteristic curve.
      The results of this study can be considered valuable in terms of the installation
      of a grid-connected PV system in fluctuated climatic conditions. 

PMID- 27035576
TI  - Neurotoxic Weapons and Syndromes.
AB  - The modern era of chemical and biological warfare began in World War I with the
      large-scale production and use of blistering and choking agents (chlorine,
      phosgene and mustard gases) in the battlefield. International treaties (the 1925
      Geneva Protocol, the 1975 Biological and Toxin Weapons Convention and the 1993
      Chemical Weapons Convention) banned biological and chemical weapons. However,
      several countries are probably still engaged in their development. Hence, there
      is risk of these weapons being used in the future. This chapter will focus on
      neurotoxic weapons (e.g. nerve agents, chemical and biological neurotoxins,
      psychostimulants), which act specifically or preeminently on the central nervous
      system and/or the neuromuscular junction. Deeply affecting the function of the
      nervous system, these agents either have incapacitating effects or cause clusters
      of casualties who manifest primary symptoms of encephalopathy, seizures, muscle
      paralysis and respiratory failure. The neurologist should be prepared both to
      notice patterns of symptoms and signs that are sufficiently consistent to raise
      the alarm of neurotoxic attacks and to define specific therapeutic interventions.
      Additionally, extensive knowledge on neurotoxic syndromes should stimulate
      scientific research to produce more effective antidotes and antibodies (which are
      still lacking for most neurotoxic weapons) for rapid administration in
      aerosolized forms in the case of terrorist or warfare scenarios. 

PMID- 27035577
TI  - Concentration of Access to Information and Communication Technologies in the
      Municipalities of the Brazilian Legal Amazon.
AB  - This study fills demand for data on access and use of information and
      communication technologies (ICT) in the Brazilian legal Amazon, a region of
      localities with identical economic, political, and social problems. We use the
      2010 Brazilian Demographic Census to compile data on urban and rural households
      (i) with computers and Internet access, (ii) with mobile phones, and (iii) with
      fixed phones. To compare the concentration of access to ICT in the municipalities
      of the Brazilian Amazon with other regions of Brazil, we use a concentration
      index to quantify the concentration of households in the following classes: with
      computers and Internet access, with mobile phones, with fixed phones, and no
      access. These data are analyzed along with municipal indicators on income,
      education, electricity, and population size. The results show that for urban
      households, the average concentration in the municipalities of the Amazon for
      computers and Internet access and for fixed phones is lower than in other regions
      of the country; meanwhile, that for no access and mobile phones is higher than in
      any other region. For rural households, the average concentration in the
      municipalities of the Amazon for computers and Internet access, mobile phones,
      and fixed phones is lower than in any other region of the country; meanwhile,
      that for no access is higher than in any other region. In addition, the study
      shows that education and income are determinants of inequality in accessing ICT
      in Brazilian municipalities and that the existence of electricity in rural
      households is directly associated with the ownership of ICT resources. 

PMID- 27035578
TI  - Vascular Changes and Neurodegeneration in the Early Stages of Diabetic
      Retinopathy: Which Comes First?
AB  - INTRODUCTION: Neurodegeneration is an early component of diabetic retinopathy
      (DR). It is unclear whether neurodegeneration is an independent factor or a
      consequence of damaged retinal vasculature. The aims of this study were to review
      the literature concerning neurodegeneration in diabetic patients without or with
      early DR, and to examine whether neurodegeneration precedes visible vasculopathy
      in the pathogenesis of DR. METHODS: A systematic literature search was performed
      to identify studies which used optical coherence tomography (OCT) or multifocal
      electroretinography (mfERG) to detect neurodegeneration in patients with no or
      mild DR as compared to healthy controls. Outcome measures were mean retinal
      thickness (RT), mean retinal nerve fiber layer (RNFL) thickness and ganglion cell
      layer (GCL) thickness. Also, mfERG amplitude and implicit time were analyzed.
      RESULTS: Eleven studies which used mfERG and/or OCT to detect neurodegeneration
      were included. Two OCT studies found significant thinning of RT, 2 found thinning
      of RNFL, whereas 1 found thickening of RT, RNFL and GCL in patients without DR.
      Two mfERG studies found a significant delay of implicit time in the same patient
      group. Retinal thinning and delay of implicit time were also detected in patients
      with mild DR. CONCLUSION: Retinal neurodegeneration is an early component of DR,
      which can precede visible vasculopathy.

PMID- 27035579
TI  - Utility of the LevelCheck Algorithm for Decision Support in Vertebral
      Localization.
AB  - STUDY DESIGN: An automatic radiographic labeling algorithm called "LevelCheck"
      was analyzed as a means of decision support for target localization in spine
      surgery. The potential clinical utility and scenarios in which LevelCheck is
      likely to be the most beneficial were assessed in a retrospective clinical data
      set (398 cases) in terms of expert consensus from a multi-reader study (three
      spine surgeons). OBJECTIVE: The aim of this study was to evaluate the potential
      utility of the LevelCheck algorithm for vertebrae localization. SUMMARY OF
      BACKGROUND DATA: Three hundred ninety-eight intraoperative radiographs and 178
      preoperative computed tomographic (CT) images for patients undergoing spine
      surgery in cervical, thoracic, lumbar regions. METHODS: Vertebral labels
      annotated in preoperative CT image were overlaid on intraoperative radiographs
      via 3D-2D registration. Three spine surgeons assessed the radiographs and
      LevelCheck labeling according to a questionnaire evaluating performance, utility,
      and suitability to surgical workflow. Geometric accuracy and registration run
      time were measured for each case. RESULTS: LevelCheck was judged to be helpful in
      42.2% of the cases (168/398), to improve confidence in 30.6% of the cases
      (122/398), and in no case diminished performance (0/398), supporting its
      potential as an independent check and assistant to decision support in spine
      surgery. The clinical contexts for which the method was judged most likely to be
      beneficial included the following scenarios: images with a lack of conspicuous
      anatomical landmarks; level counting across long spine segments; vertebrae
      obscured by other anatomy (e.g., shoulders); poor radiographic image quality; and
      anatomical variations/abnormalities. The method demonstrated 100% geometric
      accuracy (i.e., overlaid labels within the correct vertebral level in all cases)
      and did not introduce ambiguity in image interpretation. CONCLUSION: LevelCheck
      is a potentially useful means of decision support in vertebral level localization
      in spine surgery. LEVEL OF EVIDENCE: N/A.

PMID- 27035580
TI  - Fine Configuration of Thoracic Type II Meningeal Cysts: Macro- and Microscopic
      Cadaveric Study Using Epoxy Sheet Plastination.
AB  - STUDY DESIGN: A cadaveric study OBJECTIVE.: The aim of this study was to analyze
      the in situ macro- and microscopic configuration of the type II cyst and its
      anatomic relationship with surrounding structures. SUMMARY OF BACKGROUND DATA:
      The lack of consensus of surgical strategy to manage symptomatic type II
      meningeal cysts (Tarlov cysts) is because our knowledge of type II cyst anatomy
      remains incomplete. It has been assumed that the cyst communicates with the
      subarachnoid space via microconnections. Till date, however, no direct evidence
      demonstrates the existence of the microconnections, although delayed contrast
      filling of type II cysts is commonly observed in CT myelography. METHODS: Three
      type II meningeal cysts analyzed in this study were incidentally found in one of
      16 plastinated spines. The spine was from an 89-year-old female cadaver and
      plastinated as a set of 164 transverse sections with a thickness of 2.5 mm. The
      sections were examined under a stereomicroscope. RESULTS: Three type II cysts
      were in the thoracic spine and had a common feature that a clearly identifiable
      cyst neck connected the cyst body to the subarachnoid space. The dorsal root of
      the spinal nerve was centered in the cyst neck but spread over the cyst body or
      traversed the cyst cavity. The meningeal opening of the cyst was located above
      the inferior border of the vertebral pedicle, thus, the cyst neck hugged around
      the pedicle and sharply turned inferolaterally into the intervertebral foramen.
      The cyst body was halted by the dorsal ganglion. CONCLUSION: This study reveals
      in situ macro- and microscopic configuration of the type II cyst and its
      relationship with the structures and suggests that it may be feasible to localize
      and ligate the cyst neck for surgical management of type II cysts. LEVEL OF
      EVIDENCE: 3.

PMID- 27035581
TI  - Anterior Cervical Discectomy and Fusion: The Surgical Learning Curve.
AB  - STUDY DESIGN: Case-series OBJECTIVE.: The aim of the study was to investigate
      changes in intraoperative and postoperative parameters associated with the
      surgical learning curve for anterior cervical discectomy and fusion (ACDF).
      SUMMARY OF BACKGROUND DATA: ACDF is a common surgical spine procedure. The
      surgical learning curve for this procedure has not been previously characterized.
      METHODS: A prospectively maintained surgical database of consecutive patients who
      underwent primary 1-2 level ACDF for degenerative spine disease from 2006 to 2014
      was reviewed. Patients with concurrent or revision procedures were excluded. The
      series began after the surgeon's fellowship and includes his first case as an
      attending. A total of 374 patients were divided sequentially into cohorts of 125
      (early), 125 (middle), and 124 (late). Statistical analyses utilized independent
      sample t tests, chi squared tests, and multivariate regression adjusted for
      preoperative characteristics. The learning curve of operative time was
      characterized using three-parameter asymptotic regression and two separate linear
      regressions. RESULTS: The earliest cohort had a greater comorbidity burden,
      percentage of smokers, and Medicare patients, with fewer workers' compensation
      patients when compared to later cohorts. Later cohorts demonstrated decreased
      mean operative time and estimated blood loss (EBL) and increased arthrodesis
      rate. Asymptotic and linear regression analyses demonstrated that 50% of the
      learning curve occurred at case 17 and 31, respectively, whereas 90% of potential
      improvement occurred by case 56 and 57, respectively. CONCLUSION: A significant
      learning curve exists for surgeons performing ACDFs. Patients undergoing ACDF
      will experience shorter operations, less EBL, and greater arthrodesis rates as
      the surgeon gains experience. Operative proficiency can be expected to occur by
      case 60, with arthrodesis rate increasing over a longer period. These results
      suggest that despite longer operative times and increased EBL with earlier cases,
      ACDF can safely and effectively be performed at the onset of a surgeon's career.
      This conclusion may be useful to new surgeons debating between operative and
      nonoperative management of cervical degenerative disc disease. LEVEL OF EVIDENCE:
      4.

PMID- 27035582
TI  - Reoperation Rates After Anterior Cervical Discectomy and Fusion for Cervical
      Spondylotic Radiculopathy and Myelopathy: A National Population-based Study.
AB  - STUDY DESIGN: National population-based cohort study. OBJECTIVE: To compare the
      reoperation rates between cervical spondylotic radiculopathy and myelopathy in a
      national population of patients. SUMMARY OF BACKGROUND DATA: There is an
      inherently low incidence of reoperation after surgery for cervical degenerative
      disease. Therefore, it is difficult to sufficiently power studies to detect
      differences between reoperation rates of different cervical diagnoses. National
      population-based databases provide large, longitudinally followed cohorts that
      may help overcome this challenge. METHODS: We used the Korean Health Insurance
      Review and Assessment Service national database to select our study population.
      We included patients with the diagnosis of cervical spondylotic radiculopathy or
      myelopathy who underwent anterior cervical discectomy and fusion from January
      2009 to June 2014. We separated patients into two groups based on diagnosis
      codes: cervical spondylotic radiculopathy or cervical spondylotic myelopathy.
      Age, sex, presence of diabetes, osteoporosis, associated comorbidities, number of
      operated cervical disc levels, and hospital types were considered potential
      confounding factors. RESULTS: The overall reoperation rate was 2.45%. The
      reoperation rate was significantly higher in patients with cervical spondylotic
      myelopathy than in patients with cervical radiculopathy (myelopathy: P = 0.0293,
      hazard ratio = 1.433, 95% confidence interval 1.037-1.981). Male sex, presence of
      diabetes or associated comorbidities, and hospital type were noted to be risk
      factors for reoperation. CONCLUSION: The reoperation rate after anterior cervical
      discectomy and fusion was higher for cervical spondylotic myelopathy than for
      cervical spondylotic radiculopathy in a national population of patients. LEVEL OF
      EVIDENCE: 3.

PMID- 27035583
TI  - More Than 20 Years Follow-up After En Bloc Cervical Laminoplasty.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of the study was to
      evaluate clinical outcomes and to clarify the potential risks of cervical
      laminoplasty by a long-term follow-up of more than 20 years. SUMMARY OF
      BACKGROUND DATA: There is no follow-up report exceeding 20 years after cervical
      laminoplasty. METHODS: Two hundred sixteen patients underwent en bloc cervical
      laminoplasty for the treatment of cervical compressive myelopathy due to cervical
      spondylosis or ossification of the posterior longitudinal ligament between 1981
      and 1994. Of these, 148 patients with a follow-up of more than 20 years were
      retrospectively studied (68 survived patients and 80 dead patients). The
      neurological evaluation was graded using Japanese Orthopaedic Association (JOA)
      score and the recovery rate. Neurological recovery was defined by the increase in
      JOA score. Radiological examinations were carried out using pre- and
      postoperative radiographs. As for the dead patients, the cause and age of death
      were reviewed. RESULTS: The JOA score and recovery rate increased to 14.2 +/-
      2.7% and 64.9 +/- 28.6%, respectively, at 5 years. The JOA score and recovery
      rate were maintained at 13.9 +/- 3.2% and 61.6 +/- 34.6% at 10 years. The JOA
      score decreased to 11.4 +/- 5.1 at the last follow-up. In 32 out of 65 patients
      (49.2%), the JOA scores worsened mainly due to other spinal lesions. Cervical
      alignment became kyphotic when comparing preoperatively and at the last follow-up
      (ossification of the posterior longitudinal ligament: 15.7 +/- 12.2 degrees  and
      6.9 +/- 17.8 degrees , cervical spondylosis: 11.0 +/- 8.9 degrees  and 3.3 +/-
      9.4 degrees ). Range of motion (ROM) decreased and one of the causes of ROM
      reduction was interlaminar fusion. The mean age at death was 78.2 years. The most
      frequent cause of death was malignant tumor. CONCLUSION: Spine surgeons must be
      aware that patients have a long postoperative lifetime when cervical laminoplasty
      is performed. A long postoperative follow-up should be carried out after
      laminoplasty. LEVEL OF EVIDENCE: 4.

PMID- 27035584
TI  - Malnutrition Predicts Infectious and Wound Complications Following Posterior
      Lumbar Spinal Fusion.
AB  - STUDY DESIGN: A retrospective review of data collected prospectively by the
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP). OBJECTIVE: The aim of this study was to investigate the association
      between preoperative hypoalbuminemia, a marker for malnutrition, and
      complications during the 30 days following posterior lumbar fusion surgery.
      SUMMARY OF BACKGROUND DATA: Malnutrition is a potentially modifiable risk factor
      that may contribute to complications following spinal surgery. Although prior
      studies have identified associations between malnutrition, delayed wound healing,
      and surgical site infection (SSI), the evidence for such a relationship within
      spine surgery is mixed. METHODS: Patients who underwent posterior lumbar spinal
      fusion of one to three levels as part of the ACS-NSQIP were identified. Patients
      without preoperative serum albumin concentration were excluded. Outcomes were
      compared between patients with and without hypoalbuminemia (defined as serum
      albumin concentration <3.5 g/dL). All comparisons were adjusted for baseline
      differences between populations. RESULTS: Four thousand three hundred ten
      patients were included. The prevalence of hypoalbuminemia was 4.8%. In comparison
      to patients with normal albumin concentration, patients with hypoalbuminemia had
      a higher risk for occurrence of wound dehiscence [1.5% vs. 0.2%, adjusted
      relative risk (RR) = 5.8, P = 0.006], SSI (5.4% vs. 1.7%, adjusted RR = 2.3, P =
      0.010), and urinary tract infection (5.4% vs. 1.5%, adjusted RR = 2.5, P =
      0.005). Similarly, patients with hypoalbuminemia had a higher risk for unplanned
      hospital readmission within 30 days of surgery (11.7% vs. 5.4%, RR = 1.8, P <
      0.001). Finally, patients with hypoalbuminemia had a longer mean inpatient stay
      (5.2 vs. 3.7 days, RR = 1.2, P < 0.001). CONCLUSION: The present study suggests
      that malnutrition is an independent risk factor for infectious and wound
      complications following posterior lumbar fusion. Malnutrition was also associated
      with an increased length of stay and readmission. Future studies should evaluate
      methods of correcting malnutrition before lumbar spinal surgery. Such efforts
      have the potential to meaningfully decrease the rates of adverse events following
      this procedure. LEVEL OF EVIDENCE: 3.

PMID- 27035585
TI  - Can Patients With Low Back Pain Be Satisfied With Less Than Expected?
AB  - STUDY DESIGN: A prospective cohort study within care as usual. OBJECTIVE: (1) To
      explore the psychometric properties of a baseline disability questionnaire
      designed to collect patients' expectation. (2) To analyze relations between
      satisfaction with care and treatment success in patients with chronic low back
      pain (CLBP). (3) To determine the chances of being satisfied with the received
      care in absence of treatment success. SUMMARY OF BACKGROUND DATA: There is a lack
      of evidence on determinants of treatment satisfaction in patients with CLBP,
      specifically the role of patient's expectation of disability reduction after
      treatment. METHODS: Treatment expectation was measured with questions inspired by
      the Pain Disability Index (PDI) at baseline. Treatment success was considered if
      disability at the end of therapy was lower than, or equal to pretreatment
      expectation. An exploratory factor analysis was performed on the new
      questionnaire. Binary logistic regression models were used to analyze how much
      variance of satisfaction with care was explained by treatment success, pain
      disability at baseline, sex, age, duration of complaints, and pain intensity. The
      odds ratio of being satisfied when treatment was successful was calculated.
      RESULTS: Six hundred nine patients were included. The factor structure of the PDI
      expectancy had optimal fit with a one factor structure. There were low
      correlations between the expected and baseline disability, pain intensity, and
      duration of pain. Correlation between treatment success and satisfaction with
      care was low (chi = 0.13; P < 0.01). Treatment success had a low contribution to
      satisfaction with care. Of all participating patients, 51.4% were satisfied with
      care even when treatment was not successful. The odds ratio for being satisfied
      was 2.42 when treatment was successful compared to when treatment was not
      successful. CONCLUSION: The PDI-expectancy is internally consistent. Pretreatment
      expectation contributes uniquely but slightly to satisfaction with care; patients
      whose treatment was considered successful have 1.38 to 4.24 times higher chance
      of being satisfied at the end of treatment. Even when treatment was not
      successful, 51.4% of the patients with CLBP are satisfied with care. LEVEL OF
      EVIDENCE: 2.

PMID- 27035586
TI  - Rheological Properties of Viscoelastic Drops on Superamphiphobic Substrates.
AB  - The rheological properties of microliter sized drops of polymer solutions were
      investigated using measurements of their mechanical vibrational response. Drops
      were suspended on superamphiphobic substrates and vibrated by the application of
      a short mechanical impulse. Surface vibrations were monitored by refracting laser
      light through the drops and focusing the refracted light onto the surface of a
      photodiode. Time dependent variations in the photodiode output were Fourier
      transformed to obtain the frequency and spectral width of the mechanical
      resonances of the drops. These quantities were related to the frequency dependent
      shear storage and loss moduli (G' and G", respectively) using a simple
      theoretical model. The resulting rheological properties were found to be in
      agreement with microrheology measurements of the same solutions. Drop vibration
      therefore provides a fast and accurate method of quantifying the rheological
      properties of single drops.

PMID- 27035587
TI  - Sensory Agreement Guides Kinetic Energy Optimization of Arm Movements during
      Object Manipulation.
AB  - The laws of physics establish the energetic efficiency of our movements. In some
      cases, like locomotion, the mechanics of the body dominate in determining the
      energetically optimal course of action. In other tasks, such as manipulation,
      energetic costs depend critically upon the variable properties of objects in the
      environment. Can the brain identify and follow energy-optimal motions when these
      motions require moving along unfamiliar trajectories? What feedback information
      is required for such optimal behavior to occur? To answer these questions, we
      asked participants to move their dominant hand between different positions while
      holding a virtual mechanical system with complex dynamics (a planar double
      pendulum). In this task, trajectories of minimum kinetic energy were along
      curvilinear paths. Our findings demonstrate that participants were capable of
      finding the energy-optimal paths, but only when provided with veridical visual
      and haptic information pertaining to the object, lacking which the trajectories
      were executed along rectilinear paths. 

PMID- 27035588
TI  - Multiple electron transfer systems in oxygen reducing biocathodes revealed by
      different conditions of aeration/agitation.
AB  - Oxygen reducing biocathodes were formed at -0.2V/SCE (+0.04V/SHE) from compost
      leachate. Depending on whether aeration was implemented or not, two different
      redox systems responsible for the electrocatalysis of oxygen reduction were
      evidenced. System I was observed at low potential (-0.03V/SHE) on cyclic
      voltammetries (CVs). It appeared during the early formation of the biocathode
      (few hours) and resisted the hydrodynamic conditions induced by the aeration.
      System II was observed at higher potential on CV (+0.46V/SHE); it required a
      longer lag time (up to 10days) and quiescent conditions to produce an
      electrochemical signal. The hydrodynamic effects produced by the forced aeration
      led to its extinction. From their different behaviors and examples in the
      literature, system I was identified as being a membrane-bound cytochrome-related
      molecule, while system II was identified as a soluble redox mediator excreted by
      the biofilm. This study highlighted the importance of controlling the local
      hydrodynamics to design efficient oxygen reducing biocathodes able to operate at
      high potential. 

PMID- 27035589
TI  - Pd(0)@UiO-68-AP: chelation-directed bifunctional heterogeneous catalyst for
      stepwise organic transformations.
AB  - A bifunctional heterogeneous catalyst Pd(0)@UiO-68-AP based on a chelation
      directed post-synthetic approach is reported. It exhibits typical heterogeneous
      catalytic behaviour and can promote benzyl alcohol oxidiation-Knoevenagel
      condensation in a stepwise way. 

PMID- 27035590
TI  - The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell
      Lung Cancer.
AB  - BACKGROUND/AIMS: Deregulation of microRNAs (miRNAs) expression is a frequent
      event in cancer development and progression. Recent studies have implied that
      abnormal expression of miRNAs is frequently observed in non-small cell lung
      cancer (NSCLC). Here, we examined the levels and biological functions of miR-509
      5p in NSCLC. METHODS: The levels of miR-509-5p were measured by real-time
      quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with
      adjacent normal tissues. Cell viability was analyzed by MTT and colony formation
      assay. Cell migration and invasion were evaluated by transwell and wound healing
      assay. In addition, we predicted the putative targets of miR-509-5p by
      bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the
      relationship between miR-509-5p and the target in NSCLC cells. RESULTS: miR-509
      5p expression was significantly reduced in NSCLC tissues compared with adjacent
      normal tissues. In addition, miR-509-5p decreased cell proliferation, migration
      and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a
      putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells
      reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase
      reporter assay showed miR-509-5p could bind to the 3' untranslational regions of
      FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability,
      migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299
      cells. CONCLUSIONS: miR-509-5p exerts tumor-suppressive effects by attenuating
      FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR
      509-5p may be considered as a novel and potential target for the diagnosis,
      prognosis and treatment of NSCLC.

PMID- 27035591
TI  - Age and sex-based distribution of lumbar multifidus muscle atrophy and
      coexistence of disc hernia: an MRI study of 2028 patients.
AB  - PURPOSE: We aimed to investigate the prevalence of lumbar multifidus muscle (LMM)
      atrophy in patients having mechanical low back pain with and without disc hernia.
      METHODS: In total, 2028 lumbar magnetic resonance imaging scans of low back pain
      patients (age range, 18-88 years) were re-evaluated retrospectively. LMM atrophy
      was visually assessed in axial sections of L4-L5 and L5-S1 levels. RESULTS: LMM
      atrophy prevalence at both levels was significantly higher in subjects >=40 years
      compared with younger adults (P < 0.001). LMM atrophy was significantly more
      frequent in women than in men (P < 0.001). Among patients with low back pain
      without hernia, LMM atrophy was significantly more frequent than normal muscle
      (n=559 vs. n=392; P < 0.001). Frequency of LMM atrophy in low back pain patients
      without disc hernia was 13%. Hernia was more frequent in patients with LMM
      atrophy compared with patients without atrophy (P < 0.001). CONCLUSION: LMM
      atrophy is more common in women; its prevalence and severity are observed to
      increase with advancing age, and disc hernia is found more frequently in
      individuals with LMM atrophy.

PMID- 27035592
TI  - Comparison of facet joint activity on 99mTc-MDP SPECT/CT with facet joint signal
      change on MRI with fat suppression.
AB  - PURPOSE: We compared signal change on magnetic resonance imaging (MRI) with fat
      suppression and bone scan activity of lumbar facet joints to determine if these
      two imaging findings are correlated. METHODS: We retrospectively identified all
      patients who underwent imaging of the lumbar spine for pain evaluation using both
      technetium-99m methylene disphosphonate single-photon emission computed
      tomography/computed tomography (99mTc-MDP SPECT/CT) and MRI with at least one fat
      suppressed T2- or T1-weighted sequence with gadolinium enhancement within a 180
      day interval, at our institution between 1 January 2008 and 19 February 2013.
      Facet joint activity on 99mTc-MDP SPECT/CT and peri-facet signal change on MRI
      were rated as normal or increased. Agreement between the two examination types
      were determined with the kappa and prevalence-adjusted bias-adjusted kappa
      (PABAK) statistics. RESULTS: This study included 60 patients (28 male, 47%), with
      a mean age of 49+/-19.7 years (range, 12-93 years). The kappa value indicated no
      agreement between 99mTc-MDP SPECT/CT and MRI (kappa=-0.026; 95% confidence
      interval: -0.051, 0.000). The PABAK values were fair to high at each spinal
      level, which suggests that relatively low disease prevalence lowered the kappa
      values. Together, the kappa and PABAK values indicate that there is some degree
      of intermodality agreement, but that it is not consistent. CONCLUSION: Overall,
      facet joint signal change on fat-suppressed MRI did not always correlate with
      increased 99mTc-MDP SPECT/CT activity. MRI and 99mTc-MDP SPECT/CT for facet joint
      evaluation should not be considered interchangeable examinations in clinical
      practice or research.

PMID- 27035593
TI  - Behaviour of the Biological Adhesives TachoSil(r), GelitaSpon(r), and a New
      Elastic Cyanoacrylate (Adhflex(r)) in Experimental Renal Trauma and Wound
      Healing.
AB  - BACKGROUND: Renal injuries are relatively frequent in abdominal trauma. In some
      cases, adhesives and sealants can be used to repair and preserve injured organs.
      This paper describes the behaviour of three biomaterials - TachoSil(r),
      GelitaSpon(r), and a new elastic cyanoacrylate (CyA), Adhflex(r) - in
      standardized experimental renal injuries. METHODS: Ninety male Wistar rats (300
      350 g) were used. A Stiefel Biopsy Punch (8 mm diameter, 3 mm depth) was used to
      create injuries to the anterior kidney to evaluate wound healing. The animals
      were divided into five groups: (1) sham (n = 3); (2) control (n = 6), untreated,
      standard punch injury created on the anterior left kidney; (3) TachoSil(r) (n =
      27), punch injury treated with TachoSil(r); (4) GelitaSpon(r) (n = 27), punch
      injury treated with GelitaSpon(r), and (5) Adhflex(r) (n = 27), punch injury
      treated with the new elastic CyA adhesive. The parameters studied were bleeding
      time, peritoneal adhesions, and histopathological evaluation of wound healing on
      days 2, 6, and 18, including measurements of the gap between wound edges,
      inflammatory reaction (CD68), and vascular neoformation (CD31). RESULTS: The
      bleeding time was significantly shorter (27.7 +/- 12.9 s) in the Adhflex(r) group
      than in the control (135.8 +/- 11.6 s; p < 0.01), TachoSil(r) (77.5 +/- 7.4 s; p
      < 0.05), and GelitaSpon(r) (82.5 +/- 14.4 s; p < 0.05) groups. The incidence of
      intraperitoneal adhesions in the animals treated with Adhflex(r) was 3.6 times
      higher than in the non-treated group. It was also higher (p < 0.04) than in the
      groups treated with TachoSil(r) and GelitaSpon(r). The time point with the
      largest gap between the wound edges and most abundant granulation tissue was at
      day 6. The largest gap after 18 days was reported for the Adhflex(r) adhesive.
      With regard to the markers CD31 and CD68, Adhflex(r) showed the largest areas 2
      days after surgery, but no differences were found after 6 and 18 days versus the
      other treatments. The expression of the immunomarkers on the renal samples
      treated with Adhflex(r) was consistent with a normal healing process.
      CONCLUSIONS: In this experimental model of renal injuries, the new elastic CyA
      (Adhflex(r)) resulted in the shortest bleeding time. It offers rapid sealing of
      the bleeding produced by renal injuries, fixation to adjacent tissues, and
      reduced occurrences of relapse. The evolution of the scarring is similar to other
      procedures. Given that traumatic renal injuries are always an emergency due to
      haemorrhage, Adhflex(r) might offer additional benefits over conventional
      treatment methods in human clinical practice.

PMID- 27035594
TI  - Neurology and Neurologists during the Franco-Prussian War (1870-1871).
AB  - The Franco-Prussian War (1870-1871) ended with the firm establishment of the
      French Republic and with German unity under Prussian leadership. After describing
      the events leading to the war, we explain how this conflict was the first
      involving the use of machine guns; soldiers were struck down by the thousands.
      Confronted with smallpox and typhus epidemics, military surgeons were quickly
      overwhelmed and gave priority to limb injuries, considering other wounds as
      inevitably fatal. Here, we present detailed descriptions of spinal and cranial
      injuries by Leon Legouest and of asepsis prior to trepanning by Ernst von
      Bergmann. Both the war and the Commune had disastrous effects on Paris. Jean
      Martin Charcot continued to work intensely through the conflict, caring for
      numerous patients at La Salpetriere Hospital according to his son Jean-Baptiste's
      account, which we've also excerpted below. As for young Dejerine, he treated the
      wounded from France who had taken refuge in Switzerland. Desire-Magloire
      Bourneville also took heroic initiatives, as did Charles Lasegue, Alfred Vulpian,
      Alix Joffroy and Victor Cornil. 

PMID- 27035595
TI  - Black or white coffee before anaesthesia?: A randomised crossover trial.
AB  - BACKGROUND: In current preoperative fasting guidelines, coffee with milk is still
      regarded by many as solid food. Evidence on the consequences for gastric volume
      of adding milk to coffee 2 h before anaesthesia is still weak. OBJECTIVES: The
      aim of this study was to compare the gastric volume by MRI in healthy volunteers
      after drinking coffee with and without added milk. DESIGN: A randomised crossover
      trial where all participants were exposed to three coffee and milk mixtures
      performed as a noninferiority study with a predefined noninferiority limit of 12
      ml. SETTING: Department of Day Surgery and Department of Radiology, Aarhus
      University Hospital, Aarhus, Denmark. The study was conducted between August 2013
      and February 2014. PARTICIPANTS: Total 32 healthy volunteers, aged 18 to 71
      years. INTERVENTIONS: The participants fasted for 6 h for solid food, and 2 h
      before the MRI examination of gastric volume, each participant ingested one of
      three coffee mixtures: 175 ml coffee, including either 0 or 20 or 50% full fat
      milk. Each participant was studied by MRI three times separated by a minimum time
      interval of 2 days. The order of coffee mixture ingested was determined by random
      allocation. MAIN OUTCOME MEASURE: Gastric volume as measured by MRI. RESULTS: The
      mean gastric volume for black coffee was 27.8 ml, for coffee with 20% milk 17.9
      ml and for coffee with 50% milk 20.6 ml. Compared to black coffee, the gastric
      volume for 20% milk was significantly decreased with a difference of -10.0 ml
      (95% confidence interval, -18.2, -1.8), and for 50% milk it was insignificantly
      decreased, -7.2 ml (95% confidence interval, -17.4, +2.9). The upper confidence
      interval for the difference in gastric volume between the 'no milk added' group
      and each 'milk added' group did not reach the noninferiority limit of 12 ml.
      CONCLUSION: The study provides evidence that adding up to 50% full fat milk to
      coffee leads to no or only a minimal increase of the gastric volume 2 h later.
      The results support a liberalisation of policy on the addition of milk to hot
      drinks before planned anaesthesia. TRIAL REGISTRATION: www.Clinicaltrials.gov
      identifier: NCT02361632.

PMID- 27035596
TI  - A Review of Tissue Expansion-Assisted Techniques of Cleft Palate Repair.
AB  - BACKGROUND: The purpose of this report was to examine current knowledge of use of
      tissue expansion techniques to assist cleft palate repair and to review and
      contrast various techniques reported. METHODS: Two separate literature searches
      were conducted in the Cochrane Library, CINAHL, Medline and Embase databases,
      from database inception until December 2014 for use of mucoperiosteal expansion
      (MPE) and distraction osteogenesis (DO) in cleft palate repair. RESULTS: Six
      articles, reporting a total of 51 patients of palatal MPE, were identified for
      discussion and analysis. Three different MPE techniques in primary cleft palate
      repair were described: intraoperative rapid expansion, tumescent injections, and
      a 2-stage repair with an osmotic expander. Average fistula rate was 26.19%. The
      search for use of DO on palatal clefts revealed 6 animal models, a finite element
      analysis study, and 1 case report. Moreover, 2 patients were reported of the use
      of DO to assist in secondary palatal fistula closure. No fistula rate could be
      calculated due to the heterogeneity of the data. CONCLUSIONS: The experience with
      MPE in assisting cleft palate repair remains limited. Among expansion techniques,
      the use of osmotic expanders was associated with the highest rates of
      postoperative fistulae. The literature provides little evidence supporting the
      efficacy of MPE expansion in cleft palate repair. The majority of studies
      utilizing DO to assist primary cleft palate repair are in animal models with the
      exception of isolated case reports in human subjects. Although limited, the
      results demonstrate promise and the need for further research in this domain.

PMID- 27035597
TI  - An Outcomes Comparison Between Autologous and Alloplastic Cranioplasty in the
      Pediatric Population.
AB  - BACKGROUND: The use of alloplastic material in cranial reconstruction has been
      well described in the adult population, especially when a paucity of autologous
      tissue exists. In children it is unknown how long-term growth, however, may be
      affected by the implantation of nonexpansible alloplastic material. Therefore,
      the authors sought to compare the outcomes of pediatric patients undergoing
      alloplastic versus autologous cranial reconstruction. METHODS: To assess the
      safety and long-term outcomes of alloplastic cranioplasty in children, an
      institutional review board-approved, retrospective, single institution review of
      pediatric patients undergoing cranioplasty was performed from 2000 to 2014. The
      age at surgery, cause of the cranial defect, defect size, time since initial
      surgery to reconstruction, implant type, and complications were assessed.
      Postreconstruction imaging was reviewed if available. RESULTS: A reconstructive
      cranioplasty was performed in 41 pediatric patients (ages 1-19 years, average
      7.35 years). Thirty patients underwent alloplastic reconstruction (age 4.37 +/-
      5.57 years), and 11 underwent autologous reconstruction (age 2.00 +/- 3.74
      years). The size of the cranial defects was 144.01 +/- 393.04 cm for autologous
      and 405.31 +/- 572.96 cm for alloplastic reconstructions. Follow-up for all
      patients was an average of 2.33 +/- 2.76 years (0.1-9 years). No patients in
      either group showed evidence of elevated intracranial pressure after
      cranioplasty. In long-term follow-up, none of the implants were exposed or lost
      because of infection. Computed tomography and physical examination demonstrated
      that there was no skull growth restriction in either group. CONCLUSIONS: Our data
      show that alloplastic cranioplasty in the pediatric population is a safe
      alternative, when autologous cranial bone is not available.

PMID- 27035598
TI  - Extended Posterior Auricular Artery Flap for Temporo-Parietal Scalp Defect in
      Previously Irradiated Scalp.
AB  - BACKGROUND: Temperoparietal scalp defects are fairly common resulting from varied
      array of etiology. Various reconstructive options exisit, but the aim was to
      achieve a reliable and simple solution keeping in mind the principle of replacing
      "like with like." METHODS: The authors present a 83-year-old lady who had a fall
      at her home and was lying unconscious for quite some time on her right side of
      her temple, leading to full thickness necrosis of overlying scalp. She had
      received surgery and prior radiotherapy for her basal cell carcinoma of the scalp
      at the same site of her present injury. She was treated with single stage
      debridement and reconstruction using extended posterior auricalar artery flap.
      She had no issues with wound healing. DISCUSSION: Extended posterior auricular
      artery flap for tempero-parietal scalp defects is a reliable local option as it
      has the several advantages over the traditional scalp flaps. It preserves the
      direction of hair follicles, no long scalping incisions, no unsightly dog ears,
      no need for donor area grafts. In this scenario, the robustness of this flap was
      truly tested as it was raised from a previously irradiated site and did not have
      any issues of necrosis. To the best of our knowledge, this is the first report
      confirming the safety of this reliable local option postirradiation.

PMID- 27035599
TI  - Guided Surgery in Esthetic Region.
AB  - The placement of dental implants and subsequent placement of immediate temporary
      dentures after extractions has become a treatment modality accepted by the
      scientific community. In addition to the functional factor, the surgical
      procedure in a single stage in the anterior region of the maxilla offers an
      esthetic appearance, and relieves the psychological concerns of patients. To
      guarantee the success and longevity of treatments performed, the fabrication of
      surgical guides is a helpful method in these situations. Guided surgery has
      gained attention because it restores esthetics with immediate restoration,
      provides the patient with comfort in addition to dispensing with the need for
      performing surgical flaps. This auxiliary method allows the position and design
      of the implant, as well as the perforation sequence to be programmed, thus
      optimizing the clinical results. In this study, the authors present a clinical
      case of a patient who was submitted to extraction and subsequent implant
      placement with immediate loading in the anterior region of the maxilla, performed
      in a satisfactory manner. 

PMID- 27035601
TI  - Low-Grade Myofibroblastic Sarcoma of the Larynx.
AB  - Low-grade myofibroblastic sarcoma is a malignant tumor of myofibroblasts, which
      has only recently become more clearly defined. It represents a rare entity that
      progresses in a slow-growing infiltrative pattern inside deep soft tissues. Due
      to its rarity and the plasticity of the myofibroblast, it can cause significant
      diagnostic difficulties. Differencing this neoplasm from other spindle cell
      tumors requires the use of ancillary techniques such as immunohistochemistry
      and/or electron microscopy. The authors report an unusual case of low-grade
      myofibroblastic sarcoma of the larynx in a 24-year-old woman, with atypical
      clinicopathologic presentation. The patient underwent direct laryngoscopy with
      excision of the malignant mass followed by adjuvant radiation therapy. The
      authors emphasize the uncommon location of this tumor type and discuss management
      options. 

PMID- 27035602
TI  - Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar
      Bone Grafting: A Long-term Assessment.
AB  - The authors aimed to accurately assess the donor site morbidity from iliac crest
      bone grafts for secondary bone grafting in patients with cleft lip and palate
      alveolar defects. Fifty patients between 3 months and 10 years following alveolar
      bone grafting for cleft lip and palate were entered into the study. Two-thirds of
      patients had no significant concerns about the donor site. The remaining third
      had some concerns about the appearance of their hips and less than 10% of
      patients expressing strong agreement with statements about concerns with shape,
      appearance, and self-consciousness about the iliac crest donor site. Examination
      findings showed the average length of scar being 5.4 cm and a third of patients
      having some minor palpable boney irregularities of the iliac crest. The authors
      found that the alveolar crest donor site is well tolerated by patients long term
      but has a measurable morbidity long term. 

PMID- 27035603
TI  - In Response to: Platelet-Rich Fibrin Plays a Role in Healing Acute-Traumatic Ear
      Drum Perforations.

PMID- 27035604
TI  - Application Value of Selective Photon Shield in Dual-Energy Computed Tomography
      Angiography for Diagnosis of Intracranial Aneurysms.
AB  - PURPOSE: The aim of the study was to investigate the image quality of dual-energy
      computed tomography angiography (DECTA) using the selective photon shield (SPS)
      technique to diagnose intracranial aneurysms. MATERIALS AND METHODS: Eighty
      patients with a suspected intracranial aneurysm were randomly assigned to undergo
      DECTA with SPS (ie, SPS-DECTA) or DECTA without SPS (ie, DECTA). The objective
      image quality of these 2 groups was compared with digital subtraction angiography
      and surgical results as the reference. The location, number, and morphology of
      the aneurysms were evaluated between the 2 groups. The display degree and the
      size of aneurysmal neck and the diameters (ie, long and short axis) of the
      aneurysm were compared between the 2 groups. RESULTS: The signal-to-noise ratio
      and contrast-to-noise ratio of SPS-DECTA were significantly higher than those of
      DECTA (P < 0.05). The difference between the 2 groups in intracranial vascular
      subjective scoring was not statistically significant (P > 0.05). In 30 of the 40
      patients in the SPS-DECTA group, an aneurysm was detected without misdiagnosis or
      missed diagnosis. The aneurysm location, aneurysm number, and measurements by the
      2 methods were closely correlated without significant statistical differences
      (the R values were 0.953, 0.982, and 0.974, respectively; P = 0.000). The
      detection rate was 93% (26/28 patients). In the DECTA group, 2 patients were
      misdiagnosed. Mean long and short diameter and neck size by three-dimensional
      digital subtraction angiography were 5.82 +/- 3.27, 4.67 +/- 3.31, and 3.29 +/-
      1.38 mm, respectively. Aneurysm locations, number, and neck size by the 2 methods
      were closely correlated without a significant statistical difference (R values
      were 0.964, 0.968, and 0.856, respectively; P = 0.000). CONCLUSIONS: The SPS
      DECTA is very accurate for diagnosing intracranial aneurysms and could be a
      routine noninvasive screening method.

PMID- 27035605
TI  - Prognostic value of the infarct- and non-infarct like patterns and cardiovascular
      magnetic resonance parameters on long-term outcome of patients after acute
      myocarditis.
AB  - BACKGROUND: Prognostic value of the infarct- and non-infarct like patterns and
      cardiac magnetic resonance (CMR) parameters on long-term outcome of patients
      after acute myocarditis is not well known. METHODS: Between 2006 and 2015, 112
      consecutive patients with CMR-based diagnosis of acute myocarditis were
      identified in our institution. Of them, 88 were available for clinical follow-up
      and represented our studied population. Patients were divided into infarct-like
      group (n=48) (association of acute chest pain, elevated Troponin levels and ST
      elevation) and non-infarct-like group (n=40) with any other presentation. The
      composite primary endpoint of major cardiovascular events (MACE) included: all
      cause mortality, cardiac mortality, recurrence of myocarditis, heart failure, and
      sustained ventricular tachycardia. RESULTS: During follow-up, 21 patients (24%)
      experienced MACE and infarct-like patients were significantly more at risk for
      MACE than non-infarct-like patients (HR 2.4, 95% CI [1.01-5.80] p=0.04). Infarct
      like patients exhibited in particular a higher risk of sustained ventricular
      tachycardia and recurrence of myocarditis (p=0.03). They had lower CMR-derived
      left (p=0.03) and right (p=0.001) ventricular ejection fractions, and exhibited
      larger areas of late gadolinium enhancement (LGE) (p=0.001). In multivariate
      analysis, both initial NYHA functional class >II and LGE mass were independent
      predictors for long-term MACE occurrence (HR 5.8 and 1.07 per gram respectively,
      p=0.007). Moreover, a threshold of LGE mass >17g provided a high discrimination
      for MACE occurrence (AUC of 0.81). CONCLUSIONS: The infarct-like pattern of acute
      myocarditis is associated with MACE occurrence. Initial NYHA functional class >II
      and LGE are independent predictive factors of MACE during long-term follow-up
      after acute myocarditis.

PMID- 27035606
TI  - Associations of tumor necrosis factor-alpha levels and polymorphisms with
      depression in acute coronary syndrome patients.

PMID- 27035607
TI  - Red cell distribution width is a predictor of mortality in patients with chronic
      heart failure.

PMID- 27035608
TI  - Triglyceride-rich lipoproteins induce adipogenic differentiation through an
      apolipoprotein E/LRP1/caveolae-dependent pathway: A hypothesis for diet-induced
      obesity.

PMID- 27035609
TI  - Reversibly Trapping Visible Laser Light through the Catalytic Photo-oxidation of
      I(-) by Ru(bpy)3(2+).
AB  - A Gaussian, visible laser beam traveling in a hydrogel doped with NaI and
      Ru(bpy)3Cl2 spontaneously transforms into a localized, self-trapped beam, which
      propagates without diverging through the medium. The catalytic, laser-light
      induced oxidation of I(-) by [Ru(bpy)3](2+) generates I3(-) species, which create
      a refractive index increase along the beam path. The result is a cylindrical
      waveguide, which traps the optical field as bound modes and suppresses natural
      diffraction. When the beam is switched off, diffusion of I3(-) erases the
      waveguide within minutes and the system reverts to its original composition,
      enabling regeneration of the self-trapped beam. Our findings demonstrate
      reversible self-trapping for the first time in a precisely controllable,
      molecular-level photoreaction and could open routes to circuitry-free photonics
      devices powered by the interactions of switchable self-trapped beams. 

PMID- 27035610
TI  - Picture yourself: Self-focus and the endowment effect in preschool children.
AB  - When an object comes into possession, the owner will typically think that it is
      worth more than it did before they owned the item in a bias known as the
      endowment effect. This bias is particularly robust in Western societies with
      independent self-construals, but has not been observed in children below 5-6years
      of age. In three studies, we investigated whether endowment effect can be induced
      in younger children by focusing their attention on themselves. 120 children aged
      3-4years evaluated toys before and after a task where they made pictures of
      themselves, a friend or a neutral farm scene. Over the three studies, children
      consistently evaluated their own possessions, relative to other identical toys,
      more positively following the self-priming manipulation. Together these studies
      support the notion that possessions can form part of an "extended self" from
      early on in development and that the endowment effect may be due to an
      attentional self-bias framing.

PMID- 27035611
TI  - K2CO3-promoted formation of aryl esters from primary aryl amides by the acyl-acyl
      exchange process.
AB  - A new acyl-acyl exchange reaction has been developed for the formation of aryl
      esters from primary aryl amides. The reaction could occur under mild reaction
      conditions with catalytic quantities of K2CO3, and could afford moderate to good
      yields of the desired products. 

PMID- 27035612
TI  - Expression of OCT4 and SALL4 in Diffuse Large B-cell Lymphoma: An Analysis of 145
      Consecutive Cases and Testicular Lymphomas.
AB  - OCT4 and SALL4 are transcription factors within a complex network that functions
      to maintain pluripotency in primitive stem cells and germ cells. Nuclear
      expression of OCT4 is widely cited as sensitive and specific for primary and
      metastatic germ cell tumors and is commonly used in the diagnosis of central
      nervous system (CNS) germinomas. Studies have failed to systematically examine
      the expression of OCT4 or SALL4 in diffuse large B-cell lymphoma (DLBCL),
      although this entity enters the morphologic differential diagnosis of some germ
      cell tumors. A retrospective review was conducted on 145 consecutive cases of
      DLBCL and testicular lymphoma to evaluate the prevalence of OCT4 and SALL4
      expression. Nuclear OCT4 expression was present in 2/11 (18%) testicular DLBCLs
      and 6/134 (4.5%) nontesticular DLBCLs. Most OCT4 cases demonstrated moderate to
      strong expression in >50% of neoplastic cells. Rare, weak nuclear SALL4
      expression was detected in only 3 nontesticular DLBCLs. Within the
      extratesticular DLBCL group, 2/6 (33%) primary CNS DLBCLs expressed nuclear OCT4.
      In addition, OCT4 DLBCL showed an overall predilection toward non-germinal center
      B-cell phenotype (7/8; 88%) and had a higher than expected rate of CD5
      coexpression (4/8, 50%). These results are cautionary against using OCT4 as a
      sole marker of germ cell differentiation in testicular and extratesticular sites,
      especially in the CNS. The apparent associations of OCT4 expression with primary
      CNS DLBCL, non-germinal center B-cell phenotype, and CD5 coexpression raise the
      question of whether OCT4 expression in DLBCL may reflect more aggressive biology.

PMID- 27035613
TI  - In reply.

PMID- 27035614
TI  - Histologic Typing in Oropharyngeal Squamous Cell Carcinoma: A 4-Year Prospective
      Practice Study With p16 and High-Risk HPV mRNA Testing Correlation.
AB  - Oropharyngeal squamous cell carcinomas (OPSCCs) associated with human
      papillomavirus (HPV) represent a distinct clinical and pathologic entity. The
      majority of HPV-related OPSCCs have a characteristic nonkeratinizing morphology.
      This study sought to determine the strength of the association between
      nonkeratinizing histology and HPV status compared with other squamous cell
      carcinoma variants in 4 years of routine clinical practice on a high-volume head
      and neck service. Primary and/or nodal metastatic tumors in all cases of OPSCC
      from 2010 to 2013 were typed by 1 of 3 head and neck pathologists as
      keratinizing, nonkeratinizing, nonkeratinizing with maturation, or another
      defined variant. All were assessed for p16 by immunohistochemistry with a 70%
      nuclear and cytoplasmic positivity cutoff as part of routine clinical practice.
      In addition, 70 consecutive cases from 1 year were "audited" for high-risk HPV
      mRNA by reverse transcription polymerase chain reaction and in situ
      hybridization. Of the 435 cases, the majority (90%) consisted of 1 of the 3 main
      types described and the rest (10%) of uncommon variants. Nonkeratinizing
      morphology had 99.1% and 100.0% positive predictive value for p16 and high-risk
      HPV mRNA positivity, respectively. Nonkeratinizing with maturation, keratinizing,
      and other specific squamous cell carcinoma variants were p16 positive in 91.8%,
      22.8%, and 79.5%, respectively. All 47 nonkeratinizing OPSCCs tested for HPV mRNA
      were positive. In summary, strictly defined nonkeratinizing OPSCC (which
      constitutes ~55% of all tumors) essentially implies positivity for both p16 and
      transcriptionally active high-risk HPV.

PMID- 27035615
TI  - An Argument for the Use of Aminoglycosides in the Empiric Treatment of Ventilator
      Associated Pneumonia.
AB  - BACKGROUND: Appropriate empiric antibiotic therapy for ventilator-associated
      pneumonia improves outcomes. Controversy exists regarding the inclusion of
      aminoglycosides in empiric therapeutic regimens. METHODS: The Ovid and Cochrane
      databases were searched for relevant literature regarding the use of
      aminoglycosides in combination therapy for ventilator-associated pneumonia. The
      data supporting the use of aminoglycosides in certain populations and strategies
      to limit toxicity are summarized. RESULTS: In patients at high risk of infection
      with antibiotic-resistant gram-negative bacilli and in those with severe illness,
      aminoglycosides improve clinical outcomes. In critically ill populations, short
      duration therapy and high-dose extended-interval dosing of aminoglycosides can
      improve therapeutic efficacy while limiting nephrotoxicity. CONCLUSIONS: In
      selected populations using appropriate dosing strategies, aminoglycosides should
      be considered for empiric treatment of ventilator-associated pneumonia.

PMID- 27035616
TI  - Interferon lambda and hepatitis C virus core protein polymorphisms associated
      with liver cancer.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is often persistent and gradually
      advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma
      (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm.
      METHOD OF STUDY: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917,
      rs12979860 and rs12980275) and the presence of mutations in HCV core protein were
      analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without
      HCC). RESULTS: the rs12980275-AG genotype was associated with HCC on age-adjusted
      analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M
      were mainly found in genotype 1b isolates. Furthermore, a borderline level of
      statistical significance association was found among the presence of amino acid
      Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). CONCLUSIONS:
      the screening of these polymorphisms and functional studies would be useful in
      clinical practice for identifying groups at high risk of HCC development.

PMID- 27035617
TI  - A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian
      cancer cells in vitro.
AB  - Urokinase-type plasminogen activator (uPA) acts by breaking down the basement
      membrane and is involved in cell proliferation, migration and invasion. These
      actions are mediated by binding to the uPA receptor (uPAR) via its growth factor
      domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion
      protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present
      in the amyloid beta-protein precursor. Using SKOV-3 cells, an ovarian cancer cell
      line, we examined cell viability, migration, invasion and also protein
      expression. Furthermore, we examined wound healing, and migration and invasion
      using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the
      viability of ovarian cancer SKOV-3 cells in both a concentration and time
      dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The
      IC50 of uPAg-KPI was 0.5 ug/ul after 48 h treatment. At this concentration, uPAg
      KPI also inhibited tumor cell colony formation, wound closure, as well as cell
      migration and invasion capacity. At the protein level, western blot analysis
      demonstrated that uPAg-KPI exerted no significant effect on the expression of
      total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it
      suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this
      novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound
      healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by
      regulating ERK and AKT signaling. Further studies using other cell lines will
      confirm these findings.

PMID- 27035618
TI  - A novel treatment of cystic fibrosis acting on-target: cysteamine plus
      epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated
      CFTR.
AB  - We previously reported that the combination of two safe proteostasis regulators,
      cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient
      expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in
      patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of
      concept that this combination treatment restored CFTR function and reduced lung
      inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in
      Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal
      cells from patients bearing different class II CFTR mutations, either in
      homozygous or compound heterozygous form, responded to the treatment in vitro. We
      assessed individual responses to cysteamine plus EGCG in a single-centre, open
      label phase-2 trial. The combination treatment decreased sweat chloride from
      baseline, increased both CFTR protein and function in nasal cells, restored
      autophagy in such cells, decreased CXCL8 and TNF-alpha in the sputum, and tended
      to improve respiratory function. These positive effects were particularly strong
      in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity.
      However, a fraction of patients bearing other CFTR mutations failed to respond to
      therapy. Importantly, the same patients whose primary nasal brushed cells did not
      respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic
      responses in vivo. Altogether, these results suggest that the combination
      treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue
      CFTR function when autophagy is functional (in mice) and improves CFTR function
      when a rescuable protein is expressed (in mice and men). These results should
      spur the further clinical development of the combination treatment.

PMID- 27035619
TI  - NRAGE is involved in homologous recombination repair to resist the DNA-damaging
      chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell
      survival in squamous esophageal tumorigenesis.
AB  - NRAGE, a neurotrophin receptor-interacting melanoma antigen-encoding gene
      homolog, is significantly increased in the nucleus of radioresistant esophageal
      tumor cell lines and is highly upregulated to promote cell proliferation in
      esophageal carcinomas (ECs). However, whether the overexpressed NRAGE promotes
      cell growth by participating in DNA-damage response (DDR) is still unclear. Here
      we show that NRAGE is required for efficient double-strand breaks (DSBs) repair
      via homologous recombination repair (HRR) and downregulation of NRAGE greatly
      sensitizes EC cells to DNA-damaging agents both in vitro and in vivo. Moreover,
      NRAGE not only regulates the stability of DDR factors, RNF8 and BARD1, in a
      ubiquitin-proteolytic pathway, but also chaperons the interaction between BARD1
      and RNF8 via their RING domains to form a novel ternary complex. Additionally,
      the expression of NRAGE is closely correlated with RNF8 and BARD1 in esophageal
      tumor tissues. In summary, our findings reveal a novel function of NRAGE that
      will help to guide personalized esophageal cancer treatments by targeting NRAGE
      to increase cell sensitivity to DNA-damaging therapeutics in the long run.

PMID- 27035620
TI  - Restraining FOXO3-dependent transcriptional BMF activation underpins tumour
      growth and metastasis of E-cadherin-negative breast cancer.
AB  - Loss of cellular adhesion leads to the progression of breast cancer through
      acquisition of anchorage independence, also known as resistance to anoikis.
      Although inactivation of E-cadherin is essential for acquisition of anoikis
      resistance, it has remained unclear how metastatic breast cancer cells
      counterbalance the induction of apoptosis without E-cadherin-dependent cellular
      adhesion. We report here that E-cadherin inactivation in breast cancer cells
      induces PI3K/AKT-dependent FOXO3 inhibition and identify FOXO3 as a novel and
      direct transcriptional activator of the pro-apoptotic protein BMF. As a result, E
      cadherin-negative breast fail to upregulate BMF upon transfer to anchorage
      independence, leading to anoikis resistance. Conversely, expression of BMF in E
      cadherin-negative metastatic breast cancer cells is sufficient to inhibit tumour
      growth and dissemination in mice. In conclusion, we have identified repression of
      BMF as a major cue that underpins anoikis resistance and tumour dissemination in
      E-cadherin-deficient metastatic breast cancer.

PMID- 27035621
TI  - Stone heterogeneity index as the standard deviation of Hounsfield units: A novel
      predictor for shock-wave lithotripsy outcomes in ureter calculi.
AB  - We investigated whether stone heterogeneity index (SHI), which a proxy of such
      variations, was defined as the standard deviation of a Hounsfield unit (HU) on
      non-contrast computed tomography (NCCT), can be a novel predictor for shock-wave
      lithotripsy (SWL) outcomes in patients with ureteral stones. Medical records were
      obtained from the consecutive database of 1,519 patients who underwent the first
      session of SWL for urinary stones between 2005 and 2013. Ultimately, 604 patients
      with radiopaque ureteral stones were eligible for this study. Stone related
      variables including stone size, mean stone density (MSD), skin-to-stone distance,
      and SHI were obtained on NCCT. Patients were classified into the low and high SHI
      groups using mean SHI and compared. One-session success rate in the high SHI
      group was better than in the low SHI group (74.3% vs. 63.9%, P = 0.008).
      Multivariate logistic regression analyses revealed that smaller stone size (OR
      0.889, 95% CI: 0.841-0.937, P < 0.001), lower MSD (OR 0.995, 95% CI: 0.994-0.996,
      P < 0.001), and higher SHI (OR 1.011, 95% CI: 1.008-1.014, P < 0.001) were
      independent predictors of one-session success. The radiologic heterogeneity of
      urinary stones or SHI was an independent predictor for SWL success in patients
      with ureteral calculi and a useful clinical parameter for stone fragility.

PMID- 27035622
TI  - Evaluation of antiviral drug synergy in an infectious HCV system.
AB  - BACKGROUND: Direct-acting antivirals (DAAs) have greatly improved the treatment
      of HCV infection. To improve response and prevent resistance, combination
      regimens have been the focus of clinical development. Regimens are often first
      assessed in vitro, with most combination studies to date using subgenomic
      replicon systems, which do not replicate the complete HCV life cycle and preclude
      study of entry and assembly inhibitors. Infectious full-length HCV systems have
      been developed and are being used to test drug efficacy. METHODS: Using cell
      based HCV Con1b replicon and an infectious full-length HCV (HCVcc-Luc) infection
      system, we systematically tested the synergy, additivity or antagonism of
      combinations of protease, NS5A and nucleotide NS5B inhibitor classes as well as
      the combination of these DAAs with host-targeting agent cyclosporin A or non
      antibody entry inhibitor (S)-chlorcyclizine. Two computational software packages,
      MacSynergyII and CalcuSyn, were used for data analysis. RESULTS: Combinations
      between different classes showed good consistency across the two viral assay
      systems and two software platforms. Combinations between NS5A and nucleotide NS5B
      inhibitors were synergistic, while combinations of protease inhibitors with the
      other two classes were additive to slightly antagonistic. As expected,
      combinations of antivirals of the same class were additive. Combination studies
      between these DAA classes and cyclosporin A or (S)-chlorcyclizine demonstrated
      additive to synergistic effects and highly synergistic effects, respectively.
      Combinations of these drugs did not show any added or unexpected cytotoxicity.
      CONCLUSIONS: Our results show that in vitro combination studies of anti-HCV DAAs
      in the HCVcc system may provide useful guidance for drug combination designs in
      clinical studies. We also demonstrate that these DAAs in combination with host
      targeting agents or entry inhibitors may improve HCV treatment response.

PMID- 27035624
TI  - Alterations of Choroidal Thickness With Diabetic Neuropathy.
AB  - PURPOSE: To evaluate the effect of diabetic polyneuropathy on choroidal thickness
      in type 2 diabetes patients. METHODS: Forty-one diabetic polyneuropathy (DPN)
      patients with no or mild retinopathy, 50 non-DPN diabetic patients with no or
      mild retinopathy, and 42 healthy controls without any retinal complaint were
      included in the study. All participants underwent detailed ophthalmic
      examinations. Choroidal thickness (CT) measurements were performed by the same
      independent technician in the morning between 9 and 11 AM to avoid diurnal
      variations. Perpendicular CT was measured from the outer edge of the
      hyperreflective retinal pigment epithelium to the inner sclera at seven
      locations: the fovea; and 500, 1000, and 1500 MUm temporally and nasally to the
      fovea. RESULTS: The groups were age and sex matched (P > 0.05). The mean
      subfoveal CT values were significantly different in groups with a thickening
      trend from control to non-DPN and DPN (P < 0.01). The mean values for subfoveal
      CT in control, non-DPN, and DPN groups were 241.12 +/- 52.71, 279.82 +/- 51.42,
      and 304.71 +/- 54.92 MUm, respectively. The same thickening trend was also
      evident in all other six measurement points with statistical significance (P <
      0.01). CONCLUSIONS: Diabetic patients had increased CT compared to healthy
      controls. The presence of neuropathy in diabetes patients caused additional
      choroidal thickening, compared to nonneuropathic patients.

PMID- 27035623
TI  - Inactivation of the miR-183/96/182 Cluster Decreases the Severity of Pseudomonas
      aeruginosa-Induced Keratitis.
AB  - PURPOSE: The microRNA-183/96/182 cluster (miR-183/96/182) plays important roles
      in sensory organs. Because the cornea is replete with sensory innervation, we
      hypothesized that miR-183/96/182 modulates the corneal response to bacterial
      infection through regulation of neuroimmune interactions. METHODS: Eight-week-old
      miR-183/96/182 knockout (ko) mice and their wild-type littermates (wt) were used.
      The central cornea of anesthetized mice was scarred and infected with Pseudomonas
      aeruginosa (PA), strain 19660. Corneal disease was graded at 1, 3, and 5 days
      postinfection (dpi). Corneal RNA was harvested for quantitative RT-PCR.
      Polymorphonuclear neutrophils (PMN) were enumerated by myeloperoxidase assays;
      the number of viable bacteria was determined by plate counts, and ELISA assays
      were performed to determine cytokine protein levels. A macrophage (Mphi) cell
      line and elicited peritoneal PMN were used for in vitro functional assays.
      RESULTS: MicroRNA-183/96/182 is expressed in the cornea, and in Mphi and PMN of
      both mice and humans. Inactivation of miR-183/96/182 resulted in decreased
      corneal nerve density compared with wt mice. Overexpression of miR-183/96/182 in
      Mphi decreased, whereas knockdown or inactivation of miR-183/96/182 in Mphi and
      PMN increased their capacity for phagocytosis and intracellular killing of PA. In
      PA-infected corneas, ko mice showed decreased proinflammatory neuropeptides such
      as substance P and chemoattractant molecules, MIP-2, MCP1, and ICAM1; decreased
      number of PMN at 1 and 5 dpi; increased viable bacterial load at 1 dpi, but
      decreased at 5 dpi; and markedly decreased corneal disease. CONCLUSIONS: MicroRNA
      183/96/182 modulates the corneal response to bacterial infection through its
      regulation of corneal innervation and innate immunity.

PMID- 27035625
TI  - Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated
      Onset of Retinopathy in Type 1 Diabetic Individuals.
AB  - PURPOSE: We seek to identify pathogenic mechanisms for diabetic retinopathy that
      can become therapeutic targets beyond hyperglycemia and hypertension. We
      investigated if a defective myogenic response of retinal arteries to increased
      perfusion pressure, which exposes capillaries to increased pressure and flow, is
      associated with the onset of clinical retinopathy. METHODS: We examined
      prospectively the incidence of retinopathy in type 1 diabetic individuals tested
      4 years earlier for the retinal arterial myogenic response, and in a cross
      sectional study the prevalence of defective myogenic response in type 1 patients
      who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 +/
      2 years of diabetes, E-DR; n = 5) to late-onset (after 26 +/- 3 years of
      diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a
      laser Doppler blood flowmeter after a change in posture from sitting to
      reclining, which increases retinal perfusion pressure. RESULTS: Five of seven
      participants who 4 years prior had a defective myogenic response had now
      developed clinical retinopathy; as compared with only one of six participants who
      4 years prior had a normal response (P = 0.10). In the cross-sectional study, all
      participants had normal retinal hemodynamics at steady state. In response to the
      postural change, only the E-DR group showed defective myogenic response (P =
      0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood
      flow (P = 0.016 versus controls). CONCLUSIONS: In type 1 diabetic patients, a
      defective myogenic response of retinal arteries to pressure is not required for
      the development of clinical retinopathy, but is prominently associated with an
      accelerated onset of retinopathy.

PMID- 27035626
TI  - Neuropilin-1-Expressing Microglia Are Associated With Nascent Retinal Vasculature
      Yet Dispensable for Developmental Angiogenesis.
AB  - PURPOSE: Neuropilin-1 (NRP-1) is a transmembrane receptor that is critical for
      vascular development within the central nervous system (CNS). It binds and
      influences signaling of several key angiogenic factors, such as VEGF-165,
      semaphorin 3A, platelet derived growth factor, and more. Neuropilin-1 is
      expressed by neurons and endothelial cells as well as a subpopulation of
      proangiogenic macrophages/microglia that are thought to interact with endothelial
      tip cells to promote vascular anastomosis during brain vascularization. We
      previously demonstrated a significant role for NRP-1 in macrophage chemotaxis and
      showed that NRP-1-expressing microglia are major contributors to pathologic
      retinal angiogenesis. Given this influence on CNS angiogenesis, we now
      investigated the involvement of microglia-resident NRP-1 in developmental retinal
      vascularization. METHODS: We followed NRP-1 expressing microglia during retinal
      development. We used LysM-cre myeloid lineage-driver cre mice to reduce
      expression of NRP-1 in retinal myeloid-derived cells and performed a
      comprehensive morphometric analysis of retinal vasculature during development.
      RESULTS: We provide evidence that NRP-1+ microglia are present throughout the
      retina during vascular development with a preference for the non-vascularized
      retina. Using LysM-Cre/Nrp1(fl/fl) mice, we reduced NRP-1 expression by ~65% in
      retinal microglia and demonstrate that deficiency in NRP-1 in these microglia
      does not impair retinal angiogenesis. CONCLUSIONS: Our data draw a dichotomous
      role for NRP-1 in cells of myeloid lineage where it is dispensable for adequate
      retinal developmental vascularization yet obligate for pathologic retinal
      angiogenesis.

PMID- 27035627
TI  - The Epidemiology of Antisocial Behavioral Syndromes in Adulthood: Results From
      the National Epidemiologic Survey on Alcohol and Related Conditions-III.
AB  - OBJECTIVE: To present current, nationally representative US findings on
      prevalence, correlates, psychiatric comorbidity, disability, and treatment of DSM
      5 antisocial personality disorder (ASPD) and adulthood antisocial behavioral
      syndrome without conduct disorder before 15 years of age (AABS). METHOD: Face-to
      face interviews were conducted with respondents (N = 36,309) in the 2012-2013
      National Epidemiologic Survey on Alcohol and Related Conditions-III. DSM-5
      alcohol, nicotine, and specific drug use disorders and selected mood, anxiety,
      trauma-related, eating, and personality disorders were assessed using the Alcohol
      Use Disorder and Associated Disabilities Interview Schedule-5. RESULTS:
      Prevalences of ASPD and AABS were 4.3% and 20.3%, respectively, and were highest
      among male, white, Native American, younger, and unmarried respondents, those
      with high school or less education, lower incomes, and Western residence. Both
      antisocial syndromes were significantly associated with 12-month and lifetime
      substance use, dysthymia/persistent depressive, bipolar I, posttraumatic stress,
      and borderline and schizotypal personality disorders (odds ratios [ORs] = 1.2
      7.0). ASPD was additionally associated with 12-month agoraphobia and lifetime
      generalized anxiety disorder (ORs = 1.3-1.6); AABS, with 12-month and lifetime
      major depressive and 12-month generalized anxiety disorders (ORs = 1.2-1.3). Both
      were associated with significant disability (P < .001 to .01). Most antisocial
      survey respondents were untreated. CONCLUSIONS: One in 4 US adults exhibits
      syndromal antisocial behavior, with similar sociodemographic and psychiatric
      correlates and disability regardless of whether onset occurred before 15 years of
      age, illustrating the clinical and public health significance of both ASPD and
      AABS. In addition to laying groundwork for estimates of social and economic
      costs, and further etiologic and nosologic research, these findings highlight the
      urgency of effectively preventing and treating antisocial syndromes, including
      investigation of whether treatment for comorbidity hastens symptomatic remission
      and improves quality-of-life outcomes.

PMID- 27035628
TI  - Knockdown of ROS1 gene sensitizes breast tumor growth to doxorubicin in a
      syngeneic mouse model.
AB  - Treatment of breast cancer, the second leading cause of female deaths worldwide,
      with classical drugs is often accompanied by treatment failure and relapse of
      disease condition. Development of chemoresistance and drug toxicity compels
      compromising the drug concentration below the threshold level with the
      consequence of therapeutic inefficacy. Moreover, amplification and over
      activation of proto-oncogenes in tumor cells make the treatment more challenging.
      The oncogene, ROS1 which is highly expressed in diverse types of cancers
      including breast carcinoma, functions as a survival protein aiding cancer
      progression. Thus we speculated that selective silencing of ROS1 gene by carrier
      mediated delivery of siRNA might sensitize the cancer cells to the classical
      drugs at a relatively low concentration. In this investigation we showed that
      intracellular delivery of c-ROS1-targeting siRNA using pH-sensitive inorganic
      nanoparticles of carbonate apatite sensitizes mouse breast cancer cells (4T1) to
      doxorubicin, but not to cisplatin or paclitaxel, with the highest enhancement in
      chemosensitivity obtained at 40 nM of the drug concentration. Although
      intravenous administrations of ROS1-loaded nanoparticles reduced growth of the
      tumor, a further substantial effect on growth retardation was noted when the mice
      were treated with the siRNA- and Dox-bound particles, thus suggesting that
      silencing of ROS1 gene could sensitize the mouse breast cancer cells both in
      vitro and in vivo to doxorubicin as a result of synergistic effect of the gene
      knockdown and the drug action, eventually preventing activation of the survival
      pathway protein, AKT1. Our findings therefore provide valuable insight into the
      potential cross-talk between the pathways of ROS1 and doxorubicin for future
      development of effective therapeutics for breast cancer. 

PMID- 27035629
TI  - Tuning the Proximity Effect through Interface Engineering in a Pb/Graphene/Pt
      Trilayer System.
AB  - The fate of superconductivity of a nanoscale superconducting film/island relies
      on the environment; for example, the proximity effect from the substrate plays a
      crucial role when the film thicknesses is much less than the coherent length.
      Here, we demonstrate that atomic-scale tuning of the proximity effects can be
      achieved by one atomically thin graphene layer inserted between the nanoscale Pb
      islands and the supporting Pt(111) substrate. By using scanning tunneling
      microscopy and spectroscopy, we show that the coupling between the electron in a
      normal metal and the Cooper pair in an adjacent superconductor is dampened by 1
      order of magnitude via transmission through a single-atom-thick graphene. More
      interestingly, the superconductivity of the Pb islands is greatly affected by the
      moire patterns of graphene, showing the intriguing influence of the graphene
      substrate coupling on the superconducting properties of the overlayer.

PMID- 27035630
TI  - Dynamic nuclear polarization at 40 kHz magic angle spinning.
AB  - DNP-enhanced solid-state NMR spectroscopy under magic angle spinning (MAS) is
      rapidly developing into a powerful analytical tool to investigate the structure
      of a wide range of solid materials, because it provides unsurpassed sensitivity
      gains. Most developments and applications of DNP MAS NMR were so far reported at
      moderate spinning frequencies (up to 14 kHz using 3.2 mm rotors). Here, using a
      1.3 mm MAS DNP probe operating at 18.8 T and ~100 K, we show that signal
      amplification factors can be increased by up to a factor two when using smaller
      volume rotors as compared to 3.2 mm rotors, and report enhancements of around 60
      over a range of sample spinning rates from 10 to 40 kHz. Spinning at 40 kHz is
      also shown to increase (29)Si coherence lifetimes by a factor three as compared
      to 10 kHz, substantially increasing sensitivity in CPMG type experiments. The
      contribution of quenching effects to the overall sensitivity gain at very fast
      MAS is evaluated, and applications are reported on a functionalised
      mesostructured organic-inorganic material.

PMID- 27035631
TI  - Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells
      through modulation of endoplasmic reticulum stress.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have
      revolutionized the treatment for non-small cell lung cancer patients, but
      acquired resistance limit the efficiency of this treatment. As a homeostatic
      cellular recycling mechanism, autophagy has been proposed to participate in the
      EGFR-TKI resistance. However, the role of autophagy in lung cancer treatment and
      the underlying mechanisms have not been clarified. In this study, we found the
      sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal
      autophagy level. Erlotinib was able to induce autophagy not only in TKI
      sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy
      significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells
      via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this
      process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an
      executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition
      and erlotinib co-treatment induced apoptosis and prevented cancer cells from this
      co-treatment-induced cell death. Our findings suggest that autophagy inhibition
      overcomes erlotinib resistance through modulation of ER stress mediated
      apoptosis. 

PMID- 27035632
TI  - Depressive symptoms following stroke and transient ischemic attack: is it time
      for a more intensive treatment approach? results from the TABASCO cohort study.
AB  - OBJECTIVE: To examine whether depressive symptoms after a stroke or a transient
      ischemic attack (TIA) increase the risk of cognitive impairment and functional
      deterioration at 2-year follow-up. METHODS: Participants were survivors of first
      ever, mild-to-moderate ischemic stroke or TIA from the TABASCO prospective cohort
      study who underwent 3T magnetic resonance imaging and were examined by a
      multiprofessional team 6, 12, and 24 months after the event using direct
      interviews, depression scales, and neurologic, neuropsychological, and functional
      evaluations. The main outcome was the development of cognitive impairment, either
      mild cognitive impairment (MCI) or dementia. MCI was diagnosed by a decline on at
      least 1 cognitive domain (>= 1.5 SD) of the Montreal Cognitive Assessment score
      and/or on the computerized neuropsychological battery, as compared with age- and
      education-matched published norms. Dementia was diagnosed by a consensus forum
      that included senior neurologists specializing in memory disorders and a
      neuropsychologist. RESULTS: Data were obtained from 306 consecutive eligible
      patients (mean age: 67.1 +/- 10.0 years) who were admitted to the department of
      emergency medicine at the Tel Aviv Medical Center from April 1, 2008, to December
      1, 2011, within 72 hours from onset of symptoms of TIA or stroke. Of these
      patients, 51 (16.7%) developed cognitive impairment during a 2-year follow-up.
      Multivariate regression analysis showed that a Geriatric Depression Scale (GDS)
      score >= 6 at admission and at 6 months after the event was a significant
      independent marker of cognitive impairment 2 years after the stroke/TIA (OR =
      3.62, 95% CI, 1.01-13.00; OR = 3.68, 95% CI, 1.03-13.21, respectively). A higher
      GDS score at 6 months was also related to a worse functional outcome (P < .001).
      CONCLUSIONS: Our results support depression screening among stroke and TIA
      survivors as a tool to identify patients who are prone to have a worse cognitive
      and functional outcome. These patients may benefit from closer medical
      surveillance and a more intensive treatment approach. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01926691.

PMID- 27035633
TI  - Achalasia After Bariatric Surgery.
AB  - BACKGROUND: Obesity is an epidemic on the rise. Increasing body mass index (BMI)
      has been associated with a number of comorbid diseases, including rarely reported
      motility disorders such as achalasia. Motility disorders are prevalent in obese
      patients, possibly more prevalent when compared to the nonobese population.
      Identification of motility disorders is important before bariatric surgery and
      may alter the planned type of procedure performed. Limited data exist regarding
      the development or existence of esophageal motility disorders after bariatric
      surgery. This study aims to characterize patients who have undergone bariatric
      surgery and subsequently developed or were diagnosed with achalasia. METHODS:
      Patients with a diagnosis of achalasia who previously underwent bariatric surgery
      were identified. Data collected included baseline demographics, perioperative
      parameters, and postoperative outcomes. Descriptive statistics were computed for
      all variables. RESULTS: Ten patients met the inclusion criteria. All patients had
      endoscopy and manometry confirming diagnosis of achalasia after previous
      bariatric surgery. Eight patients had undergone Roux-en-Y gastric bypass (RYGB),
      and two patients had vertical banded gastroplasty (VBG). Median length of time
      from bariatric surgery to diagnosis was 6 years. Two patients had undergone
      Botox((r)) treatment, and five had gone through the scope esophageal dilations.
      All patients had a surgical intervention for achalasia, specifically Heller
      myotomy (HM) (n = 4 open, n = 4 laparoscopic) was performed in the eight RYGB
      patients, whereas near total gastrectomy and esophagectomy (n = 1), and
      transhiatal esophagectomy with a partial gastrectomy (n = 1), were performed in
      each of the patients who previously underwent VBG. These patients were considered
      to have end-stage achalasia. All patients showed significant decrease in BMI
      after bariatric surgery (11.1 +/- 1.5 kg/m(2)). Six of the eight patients who
      underwent HM achieved resolution of achalasia symptoms at a mean time of 1.6
      months and remained asymptomatic for the total follow-up of 36 months. One
      patient developed recurrent achalasia 2 years after HM and subsequently underwent
      a peroral endoscopic myotomy. One HM patient was lost to follow-up. The two
      patients who underwent esophagectomies were symptom free at 36 months.
      CONCLUSION: Although the incidence of achalasia in the bariatric population is
      unknown, it does coexist and should be treated when identified. Dysmotility is
      not uncommon and rarely is the workup completed to identify achalasia before
      bariatric surgery. Increasing our attention to identify motility diseases
      preoperatively and specifically raising awareness that achalasia can occur after
      bariatric surgery will result in better care for patients. Our results suggest
      achalasia can be effectively treated with surgical therapy after previous
      bariatric surgery.

PMID- 27035634
TI  - A Critical Comparison of Biomembrane Force Fields: Structure and Dynamics of
      Model DMPC, POPC, and POPE Bilayers.
AB  - Atomistic molecular dynamics simulations have become an important source of
      information for the structure and dynamics of biomembranes at molecular detail
      difficult to access in experiments. A number of force fields for lipid membrane
      simulations have been derived in the past; the choice of the most suitable force
      field is, however, frequently hampered by the availability of parameters for
      specific lipids. Additionally, the comparison of different quantities among force
      fields is often aggravated by varying simulation parameters. Here, we compare
      four atomistic lipid force fields, namely, the united-atom GROMOS54a7 and the all
      atom force fields CHARMM36, Slipids, and Lipid14, for a broad range of structural
      and dynamical properties of saturated and monounsaturated phosphatidylcholine
      bilayers (DMPC and POPC) as well as for monounsaturated phosphatidylethanolamine
      bilayers (POPE). Additionally, the ability of the different force fields to
      describe the gel-liquid crystalline phase transition is compared and their
      computational efficiency estimated. Moreover, membrane properties like the water
      flux across the lipid bilayer and lipid acyl chain protrusion probabilities are
      compared.

PMID- 27035635
TI  - Electrically Switchable and Permanently Stable Light Scattering Modes by Dynamic
      Fingerprint Chiral Textures.
AB  - Negative dielectric nematic liquid crystals (LCs) doped with two azobenzene
      materials provide electrically switchable and permanently stable scattering mode
      light modulators based on dynamic fingerprint chiral textures (DFCT) with
      inhomogeneously helical axes. These light modulators can be switched between
      transparent (stable large domains of DFCT) states and scattering (stable small
      domains of DFCT) states by applying electric fields with different frequencies.
      The generation of DFCT results from the long flexible side chains of the doped
      chiral dopant. That is, if the DFCT can be obtained, then the large domains of
      DFCT reflect an intrinsically stable state. Moreover, the stabilization of the
      small domains of DFCT are caused by the terminal rigid restricted side chains of
      the other doped chiral dopant. Experimentally, the required amplitude to switch
      the light modulator from a scattering (transparent) state to a transparent
      (scattering) state decreases as the frequency of the applied electric field
      increases (decreases) within the set limits. This study is the first report on
      the advantages of the light scattering mode of DFCT, including low operating
      voltage, permanently stable transmission, wide viewing angle, high contrast, and
      polarization-independent scattering and transparency.

PMID- 27035637
TI  - Ligand Influence on the Electronic Spectra of Dicationic Ruthenium-Bipyridine
      Terpyridine Complexes.
AB  - We report electronic spectra of a series of ruthenium polypyridine complexes of
      the form [(trpy)(bipy)Ru(II)-L](2+) (bipy = 2,2'-bipyridine and trpy = 2,2':6',2"
      terpyridine), where L represents a small molecular ligand that occupies the last
      coordination site. Species with L = H2O, CO2, CH3CN, and N2 were investigated in
      vacuo using photodissociation spectroscopy. All species exhibit bright metal-to
      ligand charger transfer (MLCT) bands in the visible and near UV, but with
      different spectral envelopes and peak energies, encoding the influence of the
      ligand L on the electronic structure of the complex. Several individual
      electronic bands can be resolved for L = H2O and CO2, while the spectra for L =
      N2 and CH3CN are more congested, even at low ion temperatures. The experimental
      results are discussed in the framework of time-dependent density functional
      theory. 

PMID- 27035636
TI  - Excessive Osteocytic Fgf23 Secretion Contributes to Pyrophosphate Accumulation
      and Mineralization Defect in Hyp Mice.
AB  - X-linked hypophosphatemia (XLH) is the most frequent form of inherited rickets in
      humans caused by mutations in the phosphate-regulating gene with homologies to
      endopeptidases on the X-chromosome (PHEX). Hyp mice, a murine homologue of XLH,
      are characterized by hypophosphatemia, inappropriately low serum vitamin D
      levels, increased serum fibroblast growth factor-23 (Fgf23), and osteomalacia.
      Although Fgf23 is known to be responsible for hypophosphatemia and reduced
      vitamin D hormone levels in Hyp mice, its putative role as an auto-/paracrine
      osteomalacia-causing factor has not been explored. We recently reported that
      Fgf23 is a suppressor of tissue nonspecific alkaline phosphatase (Tnap)
      transcription via FGF receptor-3 (FGFR3) signaling, leading to inhibition of
      mineralization through accumulation of the TNAP substrate pyrophosphate. Here, we
      report that the pyrophosphate concentration is increased in Hyp bones, and that
      Tnap expression is decreased in Hyp-derived osteocyte-like cells but not in Hyp
      derived osteoblasts ex vivo and in vitro. In situ mRNA expression profiling in
      bone cryosections revealed a ~70-fold up-regulation of Fgfr3 mRNA in osteocytes
      versus osteoblasts of Hyp mice. In addition, we show that blocking of increased
      Fgf23-FGFR3 signaling with anti-Fgf23 antibodies or an FGFR3 inhibitor partially
      restored the suppression of Tnap expression, phosphate production, and
      mineralization, and decreased pyrophosphate concentration in Hyp-derived
      osteocyte-like cells in vitro. In vivo, bone-specific deletion of Fgf23 in Hyp
      mice rescued the suppressed TNAP activity in osteocytes of Hyp mice. Moreover,
      treatment of wild-type osteoblasts or mice with recombinant FGF23 suppressed Tnap
      mRNA expression and increased pyrophosphate concentrations in the culture medium
      and in bone, respectively. In conclusion, we found that the cell autonomous
      increase in Fgf23 secretion in Hyp osteocytes drives the accumulation of
      pyrophosphate through auto-/paracrine suppression of TNAP. Hence, we have
      identified a novel mechanism contributing to the mineralization defect in Hyp
      mice. 

PMID- 27035638
TI  - Naive and Memory CD4+ T Cells Are Differentially Affected in Indonesian HIV
      Patients Responding to ART.
AB  - While most HIV patients beginning antiretroviral therapy (ART) with advanced
      immunodeficiency recover CD4(+) T cell numbers, the profiles and functions of the
      newly acquired CD4(+) T cells have not been monitored in a resource-limiting
      setting. In this study, HIV patients (n = 31) from Jakarta, Indonesia, were
      studied 9 months after commencing ART with nadir CD4(+) T cell counts <200
      cells/MUL. All patients were hepatitis C virus (HCV) seropositive, but
      asymptomatic. Twelve healthy age-matched controls from the same community were
      included. CD4(+) T cell subsets, immune activation (HLA-DR), and expression of
      the interleukin (IL)-7 receptor alpha chain (CD127) were quantitated by flow
      cytometry. Proliferation (expression of Ki67) was measured following in vitro
      stimulation (5 days) with anti-CD3 antibody or IL-7. Fifty-two percent of
      patients recovered CD4(+) T cell counts >200 cells/MUL over 12 months. At 9
      months, patients had fewer naive and CD31(+)-naive CD4(+) T cells, more effector
      memory (EM) CD4(+) T cells, and higher HLA-DR expression on CD4(+) T cells than
      controls. CD127 expression was low on all CD4(+) T cell subsets except for naive
      cells, where it was similar to controls. Similarly, after anti-CD3 antibody or IL
      7 stimulation, patients had lower Ki67 expression than controls in all subsets,
      except naive CD4(+) T cells where it was normal or elevated. Overall in the first
      year of ART, patients had fewer naive and more EM CD4(+) T cells. Ongoing immune
      activation and, antigen-driven stimulation and differentiation of naive T cells
      may reduce the naive T cell pool, while driving the maturation and accumulation
      of memory cells with proliferative defects.

PMID- 27035641
TI  - The effect of sulforaphane on the cell cycle, apoptosis and expression of cyclin
      D1 and p21 in the A549 non-small cell lung cancer cell line.
AB  - Sulforaphane (SFN) is present in plants belonging to Cruciferae family and was
      first isolated from broccoli sprouts. Chemotherapeutic and anticarcinogenic
      properties of sulforaphane were demonstrated, however, the underlying mechanisms
      are not fully understood. In this study we evaluated the expression of cyclin D1
      and p21 protein in SFN-treated A549 cells and correlated these results with the
      extent of cell death and/or cell cycle alterations, as well as determined a
      potential contribution of cyclin D1 to cell death. A549 cells were treated with
      increasing concentrations of SFN (30, 60 and 90 uM) for 24 h. Morphological and
      ultrastructural changes were observed using light, transmission electron
      microscope and videomicroscopy. Image-based cytometry was applied to evaluate the
      effect of SFN on apoptosis and the cell cycle. Cyclin D1 and p21 expression was
      determined by flow cytometry, RT-qPCR and immunofluorescence. siRNA was used to
      evaluate the role of cyclin D1 in the process of suforaphane-induced cell death.
      We found that the percentage of cyclin D1-positive cells decreased after the
      treatment with SFN, but at the same time mean fluorescence intensity reflecting
      cyclin D1 content was increased at 30 uM SFN and decreased at 60 and 90 uM SFN.
      Percentage of p21-positive cells increased following the treatment, with the
      highest increase at 60 uM SFN, at which concentration mean fluorescence intensity
      of this protein was also significantly increased. The 30-uM dose of SFN induced
      an increased G2/M phase population along with a decreased polyploid fraction of
      cells, which implies a functional G2/M arrest. The major mode of cell death
      induced by SFN was necrosis and, to a lower degree apoptosis. Transfection with
      cyclin D1-siRNA resulted in significantly compromised fraction of apoptotic and
      necrotic cells, which suggests that cyclin D1 is an important determinant of the
      therapeutic efficiency of SFN in the A549 cells. 

PMID- 27035645
TI  - NOB1 silencing inhibits the growth and metastasis of laryngeal cancer cells
      through the regulation of JNK signaling pathway.
AB  - Nin one binding protein (NOB1) plays important roles in the synthesis and
      degradation of proteins, thus having effects on the cellular process. In the
      present study, the expression level of NOB1 in laryngeal cancer patients was
      detected by quantitative PCR and western blotting, and the effect of NOB1 on
      growth and metastasis of laryngeal cancer cells was explored. Silence of NOB1 was
      found to inhibit the proliferation of laryngeal cancer cells, arrest cell cycle
      and induce cell apoptosis. NOB1 silence was also found to inhibit the migration
      and invasion of laryngeal cancer cells and to downregulate the protein levels of
      matrix metalloproteinases (MMPs)-2 and MMP-9. Further mechanism study revealed
      that the JNK signaling pathway was involved in the function of NOB1. Our present
      results suggest that NOB1 plays an oncogenic role in laryngeal cancer cells
      through the regulation of JNK signaling pathway, and lays a theoretical
      foundation for further exploration of NOB1. 

PMID- 27035639
TI  - Reduced Frequencies and Activation of Regulatory T Cells After the Treatment of
      HIV-1-Infected Individuals with the CCR5 Antagonist Maraviroc Are Associated with
      a Reduction in Viral Loads Rather Than a Direct Effect of the Drug on Regulatory
      T Cells.
AB  - Regulatory T cells (Tregs) play an important role in the pathogenesis of HIV-1
      infection and they frequently express the chemokine receptor CCR5. We therefore
      investigated whether antiretroviral treatment with the CCR5 antagonist Maraviroc
      affected Tregs in chronically HIV-1-infected individuals. HIV-1-infected patients
      with high viral loads had elevated frequencies of activated Tregs in the
      peripheral blood compared with healthy controls. In patients successfully treated
      with antiretroviral drugs (undetectable viral loads), the frequency and the
      activation status of Tregs were comparable with healthy controls without any
      specific effect related to the treatment with Maraviroc. These results indicate
      that the control of viral replication in general rather than a direct binding of
      Maraviroc to CCR5-positive Tregs influences Treg responses in successfully
      treated chronically HIV-1-infected individuals. 

PMID- 27035643
TI  - Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of
      photodynamic therapy in vivo.
AB  - Photodynamic therapy (PDT) exerts direct cytotoxic effects on tumor cells,
      destroys tumor blood and lymphatic vessels and induces local inflammation.
      Although PDT triggers the release of immunogenic antigens from tumor cells, the
      degree of immune stimulation is regimen-dependent. The highest immunogenicity is
      achieved at sub-lethal doses, which at the same time trigger cytoprotective
      responses, that include increased expression of glucose-regulated protein 78
      (GRP78). To mitigate the cytoprotective effects of GRP78 and preserve the
      immunoregulatory activity of PDT, we investigated the in vivo efficacy of PDT in
      combination with EGF-SubA cytotoxin that was shown to potentiate in vitro PDT
      cytotoxicity by inactivating GRP78. Treatment of immunocompetent BALB/c mice with
      EGF-SubA improved the efficacy of PDT but only when mice were treated with a dose
      of EGF-SubA that exerted less pronounced effects on the number of T and B
      lymphocytes as well as dendritic cells in mouse spleens. The observed antitumor
      effects were critically dependent on CD8+ T cells and were completely abrogated
      in immunodeficient SCID mice. All these results suggest that GRP78 targeting
      improves in vivo PDT efficacy provided intact T-cell immune system. 

PMID- 27035640
TI  - TBX5 loss-of-function mutation contributes to atrial fibrillation and atypical
      Holt-Oram syndrome.
AB  - Previous genome-wide association studies have demonstrated that single nucleotide
      polymorphisms in T-box (TBX)5 are associated with increased susceptibility to
      atrial fibrillation (AF), and a recent study has causally linked a TBX5 mutation
      to atypical Holt-Oram syndrome and paroxysmal AF. However, the prevalence and
      spectrum of TBX5 mutations in patients with AF remain to be elucidated. In the
      present study, a cohort of 190 unrelated patients with idiopathic AF were
      prospectively recruited, with 400 unrelated healthy individuals recruited as
      controls. The coding exons and flanking introns of the TBX5 gene were sequenced
      in the participants. The functional characteristics of the mutant TBX5 were
      delineated in contrast with its wild-type counterpart using a dual-luciferase
      reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.P132S,
      was identified in an index patient with AF, with a mutational prevalence of
      ~0.53%. Genetic analysis of the proband's family showed that the mutation co
      segregated with AF, and was transmitted in an autosomal dominant pattern. The
      missense mutation was absent in the 800 control chromosomes, and the altered
      amino acid was completely evolutionarily conserved across species. Functional
      analyses revealed that the mutant TBX5 had significantly reduced transcriptional
      activity. Furthermore, the mutation markedly decreased the synergistic activation
      between TBX5 and NK2 homeobox 5, another transcription factor which has been
      causatively linked to AF. The present study was the first, to the best of our
      knowledge, to report on the association between a TBX5 loss-of-function mutation
      and increased susceptibility to AF. These results provide novel insight into the
      molecular mechanism underpinning AF, and have potential implications in the
      development of novel prophylactic and therapeutic strategies for AF, the most
      common form of sustained cardiac arrhythmia. 

PMID- 27035642
TI  - Inhibition of the translocation and extracellular release of high-mobility group
      box 1 alleviates liver damage in fibrotic mice in response to D
      galactosamine/lipopolysaccharide challenge.
AB  - Acute liver injury in the setting of fibrosis is an area of interest in
      investigations, and remains to be fully elucidated. Previous studies have
      suggested the beneficial effects of liver fibrosis induced by thioacetamide and
      partial bile duct ligation against Fas-mediated acute liver injury. The
      activation of AKT and extracellular signal-regulated kinase signaling is
      considered to be crucial in this hepatoprotection. To demonstrate the protection
      of CCl4-induced liver fibrosis against lethal challenge, the present study
      compared the reactivity to lethal doses of D-galactosamine (D
      GalN)/lipopolysaccharide (LPS) between fibrotic mice and control mice groups. The
      extent of hepatic damage was assessed by survival rate and histopathological
      analysis. The molecular basis of the fibrosis-based hepatoprotection was
      examined, with a particular focus on the translocation and release of high
      mobility group box (HMGB)1 and the inflammatory response triggered by HMGB1.
      Hepatoprotection induced by fibrosis was demonstrated by improved survival rates
      (100%, vs. 20%) and improved preservation of liver architecture in fibrotic mice
      subjected to D-GalN/LPS, compared with control mice treated in the same way. D
      GalN/LPS evoked the translocation and release of HMGB1, detected by
      immunohistochemistry, in the control mice, which was significantly inhibited in
      the fibrotic mice. The gene expression levels of HMGB1-associated proinflammatory
      cytokines, including interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha
      and IL-12p40, were markedly inhibited in the fibrotic mice when exposed to D
      GalN/LPS. These findings confirmed that CCl4-based fibrosis induced
      hepatoprotection, and provided evidence that fibrosis inhibited the translocation
      and release of HMGB1, and the proinflammatory response triggered by HMGB1. This
      alleviated liver damage following exposure to D-GalN/LPS challenge. 

PMID- 27035644
TI  - Chronic Exposure of Marine Medaka (Oryzias melastigma) to 4,5-Dichloro-2-n-octyl
      4-isothiazolin-3-one (DCOIT) Reveals Its Mechanism of Action in Endocrine
      Disruption via the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis.
AB  - In this study, marine medaka (Oryzias melastigma) were chronically exposed for 28
      days to environmentally realistic concentrations of 4,5-dichloro-2-n-octyl-4
      isothiazolin-3-one (DCOIT) (0, 0.76, 2.45, and 9.86 MUg/L), the active ingredient
      in commercial antifouling agent SeaNine 211. Alterations of the hypothalamus
      pituitary-gonadal-liver (HPGL) axis were investigated across diverse levels of
      biological organization to reveal the underlying mechanisms of its endocrine
      disruptive effects. Gene transcription analysis showed that DCOIT had positive
      regulatory effects mainly in male HPGL axis with lesser extent in females. The
      stimulated steroidogenic activities resulted in increased concentrations of
      steroid hormones, including estradiol (E2), testosterone (T), and 11-KT
      testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in
      hormone homeostasis and increased E2/T ratio. The relatively estrogenic
      intracellular environment in both sexes induced the hepatic synthesis and
      increased the liver and plasma content of vitellogenin (VTG) or choriogenin.
      Furthermore, parental exposure to DCOIT transgenerationally impaired the
      viability of offspring, as supported by a decrease in hatching and swimming
      activity. Overall, the present results elucidated the estrogenic mechanisms along
      HPGL axis for the endocrine disruptive effects of DCOIT. The reproductive
      impairments of DCOIT at environmentally realistic concentrations highlights the
      need for more comprehensive investigations of its potential ecological risks.

PMID- 27035647
TI  - Inhibition of mTOR signaling protects photoreceptor cells against serum
      deprivation by reducing oxidative stress and inducing G2/M cell cycle arrest.
AB  - The mammalian target of rapamycin (mTOR) pathway is a crucial cellular signaling
      hub, which integrates internal and external cues to modulate the cell cycle,
      protein synthesis and metabolism. The present study hypothesized that inhibiting
      mTOR signaling may induce cells to enter lower and more stable bioenergetic
      states, in which neurons have greater resistance to various insults. Neurotrophin
      withdrawal from photoreceptor cells (661W cells) was mimicked using serum
      deprivation, and the neuroprotective mechanisms were studied following
      suppression of the mTOR pathway. Treatment with an mTOR specific inhibitor,
      rapamycin, reduced intracellular levels of reactive oxygen species, suppressed
      oxidative stress, and attenuated mitochondrial dysfunction. In addition,
      inhibiting mTOR signaling induced a G2/M cell cycle arrest, thus providing an
      opportunity to repair damaged DNA and block the cell death cascade. These results
      suggested that inhibition of mTOR had a neuroprotective effect on serum-deprived
      661W cells. In conclusion, the mTOR pathway is a critical molecular signal for
      cell cycle regulation and energy metabolism, and inhibiting the mTOR pathway may
      attenuate neurotrophin withdrawal-induced damage. These observations may provide
      evidence for the treatment of retinal degenerative disease, since inducing
      neurons into a lower and more stable bioenergetic state by blocking mTOR
      signaling may slow the progression of neurodegenerative diseases. 

PMID- 27035650
TI  - Involvement of mTOR and Regulation by AMPK in Early Iodine Deficiency-Induced
      Thyroid Microvascular Activation.
AB  - Iodine deficiency (ID) induces TSH-independent microvascular activation in the
      thyroid via the reactive oxygen species/nitric oxide-hypoxia-inducible factor
      1alpha/vascular endothelial growth factor (VEGF) pathway. We hypothesized the
      additional involvement of mammalian target of rapamycin (mTOR) as a positive
      regulator of this pathway and AMP-activated protein kinase (AMPK) as a negative
      feedback regulator to explain the transient nature of ID-induced microvascular
      changes under nonmalignant conditions. mTOR and AMPK involvement was investigated
      using an in vitro model (human thyrocytes in primary cultures) and 2 murine
      models of goitrogenesis (normal NMRI and RET-PTC mice [a papillary thyroid cancer
      model]). In NMRI mice, ID had no effect on the phosphorylation of ribosomal S6
      kinase (p70S6K), a downstream target of mTOR. However, rapamycin inhibited ID
      induced thyroid blood flow and VEGF protein expression. In the RET-PTC model, ID
      strongly increased the phosphorylation of p70S6K, whereas rapamycin completely
      inhibited the ID-induced increase in p70S6K phosphorylation, thyroid blood flow,
      and VEGF-A expression. In vitro, although ID increased p70S6K phosphorylation,
      the ID-stimulated hypoxia-inducible factor/VEGF pathway was inhibited by
      rapamycin. Activation of AMPK by metformin inhibited ID effects both in vivo and
      in vitro. In AMPK-alpha1 knockout mice, the ID-induced increase in thyroid blood
      flow and VEGF-A protein expression persisted throughout the treatment, whereas
      both parameters returned to control values in wild-type mice after 4 days of ID.
      In conclusion, mTOR is required for early ID-induced thyroid microvascular
      activation. AMPK negatively regulates this pathway, which may account for the
      transient nature of ID-induced TSH-independent vascular effects under benign
      conditions.

PMID- 27035648
TI  - Transcription factor-microRNA synergistic regulatory network revealing the
      mechanism of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the most common type of endocrine disorder,
      affecting 5-11% of women of reproductive age worldwide. Transcription factors
      (TFs) and microRNAs are considered to have crucial roles in the developmental
      process of several diseases and have synergistic regulatory actions. However, the
      effects of TFs and microRNAs, and the patterns of their cooperation in the
      synergistic regulatory network of PCOS, remain to be elucidated. The present
      study aimed to determine the possible mechanism of PCOS, based on a TF-microRNA
      synergistic regulatory network. Initially, the differentially expressed genes
      (DEGs) in PCOS were identified using microarray data of the GSE34526 dataset.
      Subsequently, the TFs and microRNAs which regulated the DEGs of PCOS were
      identified, and a PCOS-associated TF-microRNA synergistic regulatory network was
      constructed. This network included 195 DEGs, 136 TFs and 283 microRNAs, and the
      DEGs were regulated by TFs and microRNAs. Based on topological and functional
      enrichment analyses, SP1, mir-355-5p and JUN were identified as potentially
      crucial regulators in the development of PCOS and in characterizing the
      regulatory mechanism. In conclusion, the TF-microRNA synergistic regulatory
      network constructed in the present study provides novel insight on the molecular
      mechanism of PCOS in the form of synergistic regulated model. 

PMID- 27035646
TI  - Time-dependent activity of Na+/H+ exchanger isoform 1 and homeostasis of
      intracellular pH in astrocytes exposed to CoCl2 treatment.
AB  - Hypoxia causes injury to the central nervous system during stroke and has
      significant effects on pH homeostasis. Na+/H+ exchanger isoform 1 (NHE1) is
      important in the mechanisms of hypoxia and intracellular pH (pHi) homeostasis. As
      a well-established hypoxia-mimetic agent, CoCl2 stabilizes and increases the
      expression of hypoxia inducible factor-1alpha (HIF-1alpha), which regulates
      several genes involved in pH balance, including NHE1. However, it is not fully
      understood whether NHE1 is activated in astrocytes under CoCl2 treatment. In the
      current study, pHi and NHE activity were analyzed using the pHi-sensitive dye
      BCECF-AM. Using cariporide (an NHE1-specific inhibitor) and EIPA (an NHE
      nonspecific inhibitor), the current study demonstrated that it was NHE1, not the
      other NHE isoforms, that was important in regulating pHi homeostasis in
      astrocytes during CoCl2 treatment. Additionally, the present study observed that,
      during the early period of CoCl2 treatment (the first 2 h), NHE1 activity and pHi
      dropped immediately, and NHE1 mRNA expression was reduced compared with control
      levels, whereas expression levels of the NHE1 protein had not yet changed. In the
      later period of CoCl2 treatment, NHE1 activity and pHi significantly increased
      compared with the control levels, as did the mRNA and protein expression levels
      of NHE1. Furthermore, the cell viability and injury of astrocytes was not changed
      during the initial 8 h of CoCl2 treatment; their deterioration was associated
      with the higher levels of pHi and NHE1 activity. The current study concluded that
      NHE1 activity and pHi homeostasis are regulated by CoCl2 treatment in a time
      dependent manner in astrocytes, and may be responsible for the changes in cell
      viability and injury observed under hypoxia-mimetic conditions induced by CoCl2
      treatment. 

PMID- 27035657
TI  - Functionally conserved effects of rapamycin exposure on zebrafish.
AB  - Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase
      important in cell proliferation, growth and protein translation. Rapamycin, a
      well-known anti-cancer agent and immunosuppressant drug, inhibits mTOR activity
      in different taxa including zebrafish. In the present study, the effect of
      rapamycin exposure on the transcriptome of a zebrafish fibroblast cell line, ZF4,
      was investigated. Microarray analysis demonstrated that rapamycin treatment
      modulated a large set of genes with varying functions including protein
      synthesis, assembly of mitochondrial and proteasomal machinery, cell cycle,
      metabolism and oxidative phosphorylation in ZF4 cells. A mild however,
      coordinated reduction in the expression of proteasomal and mitochondrial
      ribosomal subunits was detected, while the expression of numerous ribosomal
      subunits increased. Meta-analysis of heterogeneous mouse rapamycin microarray
      datasets enabled the comparison of zebrafish and mouse pathways modulated by
      rapamycin, using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology
      pathway analysis. The analyses demonstrated a high degree of functional
      conservation between zebrafish and mice in response to rapamycin. In addition,
      rapamycin treatment resulted in a marked dose-dependent reduction in body size
      and pigmentation in zebrafish embryos. The present study is the first, to the
      best of our knowledge, to evaluate the conservation of rapamycin-modulated
      functional pathways between zebrafish and mice, in addition to the dose-dependent
      growth curves of zebrafish embryos upon rapamycin exposure. 

PMID- 27035652
TI  - Gestational Hypothyroidism Improves the Ability of the Female Offspring to Clear
      Streptococcus pneumoniae Infection and to Recover From Pneumococcal Pneumonia.
AB  - Maternal thyroid hormones are essential for proper fetal development. A deficit
      of these hormones during gestation has enduring consequences in the central
      nervous system of the offspring, including detrimental learning and impaired
      memory. Few studies have shown that thyroid hormone deficiency has a transient
      effect in the number of T and B cells in the offspring gestated under
      hypothyroidism; however, there are no studies showing whether maternal
      hypothyroidism during gestation impacts the response of the offspring to
      infections. In this study, we have evaluated whether adult mice gestated in
      hypothyroid mothers have an altered response to pneumococcal pneumonia. We
      observed that female mice gestated in hypothyroidism have increased survival rate
      and less bacterial dissemination to blood and brain after an intranasal challenge
      with Streptococcus pneumoniae. Further, these mice had higher amounts of
      inflammatory cells in the lungs and reduced production of cytokines
      characteristic of sepsis in spleen, blood, and brain at 48 hours after infection.
      Interestingly, mice gestated in hypothyroid mothers had basally increased
      vascular permeability in the lungs. These observations suggest that gestational
      hypothyroidism alters the immune response and the physiology of lungs in the
      offspring, increasing the resistance to respiratory bacterial infections.

PMID- 27035655
TI  - CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice.
AB  - Circadian misalignment induces insulin resistance in both human and animal
      models, and skeletal muscle is the largest organ response to insulin. However,
      how circadian clock regulates muscle insulin sensitivity and the underlying
      molecular mechanisms are still largely unknown. Here we show circadian locomotor
      output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor
      nuclear translocator-like protein (BMAL)-1, two core circadian transcription
      factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse
      skeletal muscle. Furthermore, insulin signaling is attenuated in the skeletal
      muscle of Clock(Delta19/Delta19) mice, and knockdown of CLOCK or BMAL1 by small
      interfering RNAs induces insulin resistance in C2C12 myotubes. Consistently,
      ectopic expression of CLOCK and BMAL1 improves insulin sensitivity in C2C12
      myotubes. Moreover, CLOCK and BMAL1 regulate the expression of sirtuin 1 (SIRT1),
      an important regulator of insulin sensitivity, in C2C12 myotubes and mouse
      skeletal muscle, and two E-box elements in Sirt1 promoter are responsible for its
      CLOCK- and BMAL1-dependent transcription in muscle cells. Further studies show
      that CLOCK and BMAL1 regulate muscle insulin sensitivity through SIRT1. In
      addition, we find that BMAL1 and SIRT1 are decreased in the muscle of mice
      maintained in constant darkness, and resveratrol supplementation activates SIRT1
      and improves insulin sensitivity. All these data demonstrate that CLOCK and BMAL1
      regulate muscle insulin sensitivity via SIRT1, and activation of SIRT1 might be a
      potential valuable strategy to attenuate muscle insulin resistance related to
      circadian misalignment.

PMID- 27035653
TI  - Long-Term Exposure of Pancreatic beta-Cells to Palmitate Results in SREBP-1C
      Dependent Decreases in GLP-1 Receptor Signaling via CREB and AKT and Insulin
      Secretory Response.
AB  - The effects of prolonged exposure of pancreatic beta-cells to high saturated
      fatty acids on glucagon-like peptide-1 (GLP-1) action were investigated. Murine
      islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to
      palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured
      by real-time RT-PCR and immunoblotting, respectively. Specific short interfering
      RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1.
      Insulin release was assessed with a specific ELISA. Exposure of murine islets, as
      well as of human and INS-1E beta-cells, to palmitate reduced the ability of
      exendin-4 to augment insulin mRNA levels, protein content, and release. In
      addition, palmitate blocked exendin-4-stimulated cAMP-response element-binding
      protein and v-akt murine thymoma viral oncogene homolog phosphorylation, whereas
      phosphorylation of MAPK-ERK kinase-1/2 and ERK-1/2 was not altered. Similarly,
      RNA interference-mediated suppression of Glp1r expression prevented exendin-4
      induced cAMP-response element-binding protein and v-akt murine thymoma viral
      oncogene homolog phosphorylation, but did not impair exendin-4 stimulation of
      MAPK-ERK kinase-1/2 and ERK-1/2. Both islets from mice fed a high fat diet and
      human and INS-1E beta-cells exposed to palmitate showed reduced GLP-1 receptor
      and pancreatic duodenal homeobox-1 (PDX-1) and increased sterol regulatory
      element-binding protein (SREBP-1C) mRNA and protein levels. Furthermore,
      suppression of SREBP-1C protein expression prevented the reduction of PDX-1 and
      GLP-1 receptor levels and restored exendin-4 signaling and action. Finally,
      treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP
      1C expression, increased PDX-1 and GLP-1 receptor levels, consequently,
      enhancement of exendin-4-induced insulin release. Palmitate impairs exendin-4
      effects on beta-cells by reducing PDX-1 and GLP-1 receptor expression and
      signaling in a SREBP-1C-dependent manner. Metformin counteracts the impairment of
      GLP-1 receptor signaling induced by palmitate.

PMID- 27035649
TI  - Cardiac-Specific Disruption of GH Receptor Alters Glucose Homeostasis While
      Maintaining Normal Cardiac Performance in Adult Male Mice.
AB  - GH is considered necessary for the proper development and maintenance of several
      tissues, including the heart. Studies conducted in both GH receptor null and
      bovine GH transgenic mice have demonstrated specific cardiac structural and
      functional changes. In each of these mouse lines, however, GH-induced signaling
      is altered systemically, being decreased in GH receptor null mice and increased
      in bovine GH transgenic mice. Therefore, to clarify the direct effects GH has on
      cardiac tissue, we developed a tamoxifen-inducible, cardiac-specific GHR
      disrupted (iC-GHRKO) mouse line. Cardiac GH receptor was disrupted in 4-month-old
      iC-GHRKO mice to avoid developmental effects due to perinatal GHR gene
      disruption. Surprisingly, iC-GHRKO mice showed no difference vs controls in
      baseline or postdobutamine stress test echocardiography measurements, nor did iC
      GHRKO mice show differences in longitudinal systolic blood pressure measurements.
      Interestingly, iC-GHRKO mice had decreased fat mass and improved insulin
      sensitivity at 6.5 months of age. By 12.5 months of age, however, iC-GHRKO mice
      no longer had significant decreases in fat mass and had developed glucose
      intolerance and insulin resistance. Furthermore, investigation via immunoblot
      analysis demonstrated that iC-GHRKO mice had appreciably decreased insulin
      stimulated Akt phosphorylation, specifically in heart and liver, but not in
      epididymal white adipose tissue. These changes were accompanied by a decrease in
      circulating IGF-1 levels in 12.5-month-old iC-GHRKO mice. These data indicate
      that whereas the disruption of cardiomyocyte GH-induced signaling in adult mice
      does not affect cardiac function, it does play a role in systemic glucose
      homeostasis, in part through modulation of circulating IGF-1.

PMID- 27035658
TI  - Effect of Groove Surface Texture on Tribological Characteristics and Energy
      Consumption under High Temperature Friction.
AB  - Energy consumption and tribological properties could be improved by proper design
      of surface texture in friction. However, some literature focused on investigating
      their performance under high temperature. In the study, different groove surface
      textures were fabricated on steels by a laser machine, and their tribological
      behaviors were experimentally studied with the employment of the friction and
      wear tester under distinct high temperature and other working conditions. The
      friction coefficient was recorded, and wear performance were characterized by
      double light interference microscope, scanning electron microscope (SEM) and x
      ray energy dispersive spectrometry (EDS). Then, the performances of energy
      consumptions were carefully estimated. Results showed that friction coefficient,
      wear, and energy consumption could almost all be reduced by most textures under
      high temperature conditions, but to a different extent which depends on the
      experimental conditions and texture parameters. The main improvement mechanisms
      were analyzed, such as the hardness change, wear debris storage, thermal stress
      release and friction induced temperature reduction by the textures. Finally, a
      scattergram of the relatively reduced ratio of the energy consumption was drawn
      for different surface textures under four distinctive experimental conditions to
      illustrate the comprehensive energy consumption improving ability of textures,
      which was of benefit for the application of texture design. 

PMID- 27035651
TI  - Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation
      and Withdrawal.
AB  - Human endometrial stromal decidualization is required for embryo receptivity,
      angiogenesis, and placentation. Previous studies from our laboratories
      established that connexin (Cx)-43 critically regulates endometrial stromal cell
      (ESC) differentiation, whereas gap junction blockade prevents it. The current
      study evaluated the plasticity of ESC morphology and Cx43 expression, as well as
      other biochemical markers of cell differentiation, in response to decidualizing
      hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM
      progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal
      for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was
      documented by characteristic changes in cell shape. Cx43 was reversibly up- and
      down-regulated after the estradiol, progesterone, and cAMP treatment and
      withdrawal, respectively, paralleled by fluctuations in prolactin, vascular
      endothelial growth factor, IL-11, and glycodelin secretion. Markers of
      mesenchymal-epithelial transition (MET), and its counterpart epithelial
      mesenchymal transition, followed reciprocal patterns corresponding to the
      morphological changes. Incubation in the presence of 18alpha-glycyrrhetinic acid,
      an inhibitor of gap junctions, partially reversed the expression of
      decidualization and MET markers. In the absence of hormones, Cx43 overexpression
      promoted increases in vascular endothelial growth factor and IL-11 secretion, up
      regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal
      transition marker. The combined results support the hypothesis that Cx43
      containing gap junctions and endocrine factors cooperate to regulate selected
      biomarkers of stromal decidualization and MET and suggest roles for both
      phenomena in endometrial preparation for embryonic receptivity.

PMID- 27035654
TI  - Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved
      Cytokine Pathways in Rainbow Trout.
AB  - Although disease and infection is associated with attenuated growth, the
      molecular pathways involved are poorly characterized. We postulated that the IGF
      axis, a central governor of vertebrate growth, is repressed during infection to
      promote resource reallocation towards immunity. This hypothesis was tested in
      rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a
      Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at
      hatch, first feeding, and 3 weeks after first feeding. Quantitative
      transcriptional profiling was performed for genes encoding both IGF hormones, 19
      salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and
      immune status. There were major differences in the developmental response of the
      IGF axis to AS and VHSv, with the VHSv challenge causing strong down-regulation
      of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes, each negative
      regulators of IGF signaling, were highly induced by AS and VHSv in striking
      correlation with host defense genes regulated by cytokine pathways. Follow-up
      experiments demonstrated a highly significant coregulation of IGFBP-1A1 and IGFBP
      6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and
      head kidney) when trout were challenged by a different Gram-negative bacterium,
      Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP
      subtypes are directly regulated by cytokine signaling pathways, allowing
      immediate modulation of growth and/or immune system phenotypes according to the
      level of activation of immunity. Our findings provide new and comprehensive
      insights into cross talk between conserved pathways regulating teleost growth,
      development, and immunity.

PMID- 27035656
TI  - Cellular Pathophysiology of an Adrenal Adenoma-Associated Mutant of the Plasma
      Membrane Ca(2+)-ATPase ATP2B3.
AB  - Adrenal aldosterone-producing adenomas (APAs) are a main cause for primary
      aldosteronism leading to arterial hypertension. Physiologically, aldosterone
      production in the adrenal gland is stimulated by angiotensin II and high
      extracellular potassium. These stimuli lead to a depolarization of the plasma
      membrane and, as a consequence, an increase of intracellular Ca(2+). Mutations of
      the plasma membrane Ca(2+)-ATPase ATP2B3 have been found in APAs with a
      prevalence of 0.6%-3.1%. Here, we investigated the effects of the APA-associated
      ATP2B3(Leu425_Val426del) mutation in adrenocortical NCI-H295R and human embryonic
      kidney (HEK-293) cells. Ca(2+) measurements revealed a higher basal Ca(2+) level
      in cells expressing the mutant ATP2B3. This rise in intracellular Ca(2+) was even
      more pronounced under conditions with high extracellular Ca(2+) pointing to an
      increased Ca(2+) influx associated with the mutated protein. Furthermore, cells
      with the mutant ATP2B3 appeared to have a reduced capacity to export Ca(2+)
      suggesting a loss of the physiological pump function. Surprisingly, expression of
      the mutant ATP2B3 caused a Na(+)-dependent inward current that strongly
      depolarized the plasma membrane and compromised the cytosolic cation composition.
      In parallel to these findings, mRNA expression of the cytochrome P450, family 11,
      subfamily B, polypeptide 2 (aldosterone synthase) was substantially increased and
      aldosterone production was enhanced in cells overexpressing mutant ATP2B3. In
      summary, the APA-associated ATP2B3(Leu425_Val426del) mutant promotes aldosterone
      production by at least 2 different mechanisms: 1) a reduced Ca(2+) export due to
      the loss of the physiological pump function; and 2) an increased Ca(2+) influx
      due to opening of depolarization-activated Ca(2+) channels as well as a possible
      Ca(2+) leak through the mutated pump.

PMID- 27035659
TI  - Oncogene-mediated tumor transformation sensitizes cells to autophagy induction.
AB  - The process of tumorigenesis induces alterations in numerous cellular pathways
      including the main eukaryotic metabolic routes. It has been recently demonstrated
      that autophagy is part of the oncogene-induced senescence phenotype although its
      role in tumor establishment has not been completely clarified. In the present
      study, we showed that non-transformed cells are sensitized to mitochondrial
      stress and autophagy induction when they are transformed by oncogenes such as c
      Myc or Ras. We observed that overexpression of c-Myc or Ras increased AMP
      activated protein kinase (AMPK) phosphorylation and the expression of p62, a
      known partner for degradation by autophagy. The activation of AMPK was found to
      favor the activation of FoxO3 which was prevented by the inhibition of AMPK. The
      transcriptional activation mediated by FoxO3 upregulated genes such as BNIP3 and
      LC3. Finally, the transformation by oncogenes such as c-Myc and Ras predisposes
      tumor cells to autophagy induction as a consequence of mitochondrial stress and
      impairs tumor growth in vitro and in vivo, which may have therapeutic
      implications. 

PMID- 27035660
TI  - Comparison of the Deep Optic Nerve Head Structure between Normal-Tension Glaucoma
      and Nonarteritic Anterior Ischemic Optic Neuropathy.
AB  - PURPOSE: To compare the deep optic nerve head (ONH) structure between normal
      tension glaucoma (NTG) and nonarteritic anterior ischemic optic neuropathy
      (NAION) and also in healthy subjects as a control using enhanced depth imaging
      (EDI) spectral-domain optical coherence tomography (SD-OCT). METHODS: This
      prospective cross-sectional study included 21 NAION patients who had been
      diagnosed as NAION at least 6 months prior to study entry, and 42 NTG patients
      and 42 healthy controls who were matched with NAION patients in terms of age,
      intraocular pressure (IOP), and optic disc area. The retinal nerve fiber layer
      (RNFL) thickness in the affected sector was also matched between NAION and NTG
      patients. The ONH was imaged using SD-OCT with the EDI technique. The anterior
      lamina cribrosa surface depth (LCD) and average prelaminar tissue (PT) thickness
      were measured in a sector of interest in each eye and compared among the three
      groups. RESULTS: In the sector-matched comparison, LCD was largest in NTG
      patients, followed by NAION patients, while PT was thinner in NTG patients than
      in NAION patients (all P < 0.001). NAION patients had a comparable LCD and a
      thinner PT relative to normal controls (P = 0.170 and < 0.001, respectively).
      CONCLUSION: The deep ONH configuration is strikingly different between NTG and
      NAION. The differing features provide comparative insight into the
      pathophysiology of the two diseases, and may be useful for differential
      diagnosis.

PMID- 27035661
TI  - New Trypanosoma evansi Type B Isolates from Ethiopian Dromedary Camels.
AB  - BACKGROUND: Trypanosoma (T.) evansi is a dyskinetoplastic variant of T. brucei
      that has gained the ability to be transmitted by all sorts of biting flies. T.
      evansi can be divided into type A, which is the most abundant and found in
      Africa, Asia and Latin America and type B, which has so far been isolated only
      from Kenyan dromedary camels. This study aimed at the isolation and the genetic
      and phenotypic characterisation of type A and B T. evansi stocks from camels in
      Northern Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: T. evansi was isolated in mice
      by inoculation with the cryopreserved buffy coat of parasitologically confirmed
      animals. Fourteen stocks were thus isolated and subject to genotyping with PCRs
      targeting type-specific variant surface glycoprotein genes, mitochondrial
      minicircles and maxicircles, minisatellite markers and the F1-ATP synthase gamma
      subunit gene. Nine stocks corresponded to type A, two stocks were type B and
      three stocks represented mixed infections between A and B, but not hybrids. One
      T. evansi type A stock was completely akinetoplastic. Five stocks were adapted to
      in vitro culture and subjected to a drug sensitivity assay with melarsomine
      dihydrochloride, diminazene diaceturate, isometamidium chloride and suramin. In
      vitro adaptation induced some loss of kinetoplasts within 60 days. No correlation
      between drug sensitivity and absence of the kinetoplast was observed. Sequencing
      the full coding sequence of the F1-ATP synthase gamma subunit revealed new type
      specific single nucleotide polymorphisms and deletions. CONCLUSIONS/SIGNIFICANCE:
      This study addresses some limitations of current molecular markers for T. evansi
      genotyping. Polymorphism within the F1-ATP synthase gamma subunit gene may
      provide new markers to identify the T. evansi type that do not rely on variant
      surface glycoprotein genes or kinetoplast DNA.

PMID- 27035662
TI  - Interaction between Ammonium Toxicity and Green Tide Development Over Seagrass
      Meadows: A Laboratory Study.
AB  - Eutrophication affects seagrasses negatively by increasing light attenuation
      through stimulation of biomass of fast-growing, bloom-forming algae and because
      high concentrations of ammonium in the water can be toxic to higher plants. We
      hypothesized nevertheless, that moderate amounts of nitrophilic macroalgae that
      coexists with seagrasses under eutrophic conditions, can alleviate the harmful
      effects of eutrophication on seagrasses by reducing ammonium concentrations in
      the seawater to non-toxic levels because such algae have a very large capacity to
      take up inorganic nutrients. We studied therefore how combinations of different
      ammonium concentrations (0, 25 and 50 MUM) and different standing stocks of
      macroalgae (i.e. 0, 1 and 6 layers of Ulva sp.) affected survival, growth and net
      production of the seagrass Zostera noltei. In the absence of Ulva sp., increasing
      ammonium concentrations had a negative influence on the performance of Z. noltei.
      The presence of Ulva sp. without ammonium supply had a similar, but slightly
      smaller, negative effect on seagrass fitness due to light attenuation. When
      ammonium enrichment was combined with presence of Ulva sp., Ulva sp. ameliorated
      some of negative effects caused by high ammonium availability although Ulva sp.
      lowered the availability of light. Benthic microalgae, which increased in biomass
      during the experiment, seemed to play a similar role as Ulva sp.--they
      contributed to remove ammonium from the water, and thus, aided to keep the
      ammonium concentrations experienced by Z. noltei at relatively non-toxic levels.
      Our findings show that moderate amounts of drift macroalgae, eventually combined
      with increasing stocks of benthic microalgae, may aid seagrasses to alleviate
      toxic effects of ammonium under eutrophic conditions, which highlights the
      importance of high functional diversity for ecosystem resistance to anthropogenic
      disturbance.

PMID- 27035663
TI  - Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in
      Obesity.
AB  - RATIONALE: Obesity is characterized by increased systemic and pulmonary blood
      volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane
      diffusion suggests subclinical interstitial edema. In this setting, functional
      abnormalities should encompass the entire distal lung including the airways.
      OBJECTIVES: We hypothesize that in obesity: 1) pulmonary vascular congestion will
      affect the distal lung unit with concordant alveolar membrane and distal airway
      abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction
      will relate to the cardiac response. METHODS: 54 non-smoking obese subjects
      underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with
      partition into membrane diffusion (DM) and capillary blood volume (VC), and
      cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by
      calculation of DM/VC. MEASUREMENTS AND MAIN RESULTS: Mean age was 45+/-12 years;
      mean BMI was 44.8+/-7 kg/m2. Vital capacity was 88+/-13% predicted with reduction
      in functional residual capacity (58+/-12% predicted). Despite normal DLCO (98+/
      18% predicted), VC was elevated (135+/-31% predicted) while DM averaged 94+/-22%
      predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment
      of alveolar membrane and low values indicating alveolar membrane dysfunction. The
      most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31,
      p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body
      surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p =
      0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in
      the normal range despite presence of obesity. CONCLUSIONS: Global dysfunction of
      the distal lung (alveolar membrane and distal airway) is associated with
      pulmonary vascular congestion and failure to achieve the high output state of
      obesity. Pulmonary vascular congestion and consequent fluid transudation and/or
      alterations in the structure of the alveolar capillary membrane may be considered
      often unrecognized causes of airway dysfunction in obesity.

PMID- 27035664
TI  - ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and
      Migration of Vascular Endothelial Cells.
AB  - Estrogen promotes the proliferation and migration of vascular endothelial cells
      (ECs), which likely underlies its ability to accelerate re-endothelialization and
      reduce adverse remodeling after vascular injury. In previous studies, we have
      shown that the protective effects of E2 (the active endogenous form of estrogen)
      in vascular injury require the estrogen receptor alpha (ERalpha). ERalpha
      transduces the effects of estrogen via a classical DNA binding, "genomic"
      signaling pathway and via a more recently-described "rapid" signaling pathway
      that is mediated by a subset of ERalpha localized to the cell membrane. However,
      which of these pathways mediates the effects of estrogen on endothelial cells is
      poorly understood. Here we identify a triple point mutant version of ERalpha (KRR
      ERalpha) that is specifically defective in rapid signaling, but is competent to
      regulate transcription through the "genomic" pathway. We find that in ECs
      expressing wild type ERalpha, E2 regulates many genes involved in cell migration
      and proliferation, promotes EC migration and proliferation, and also blocks the
      adhesion of monocytes to ECs. ECs expressing KRR mutant ERalpha, however, lack
      all of these responses. These observations establish KRR ERalpha as a novel tool
      that could greatly facilitate future studies into the vascular and non-vascular
      functions of ERalpha rapid signaling. Further, they support that rapid signaling
      through ERalpha is essential for many of the transcriptional and physiological
      responses of ECs to E2, and that ERalpha rapid signaling in ECs, in vivo, may be
      critical for the vasculoprotective and anti-inflammatory effects of estrogen. 

PMID- 27035665
TI  - Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway.
AB  - Astaxanthin is an oxygen-containing derivative of carotenoids that effectively
      suppresses reactive oxygen and has nutritional and medicinal value. The
      mechanisms underlying the effects of astaxanthin on isoflurane-induced
      neuroapoptosis remain to be fully understood. The present study was conducted to
      evaluate the protective effect of astaxanthin to reduce isoflurane-induced
      neuroapoptosis and to investigate the underlying mechanisms. The results
      demonstrated that isoflurane induced brain damage, increased caspase-3 activity
      and suppressed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)
      signaling pathway in an in vivo model. However, treatment with astaxanthin
      significantly inhibited brain damage, suppressed caspase-3 activity and
      upregulated the PI3K/Akt pathway in the isoflurane-induced rats. Furthermore,
      isoflurane suppressed cell growth, induced cell apoptosis, enhanced caspase-3
      activity and downregulated the PI3K/Akt pathway in organotypic hippocampal slice
      culture. Administration of astaxanthin significantly promoted cell growth,
      reduced cell apoptosis and caspase-3 activity, and upregulated the PI3K/Akt
      pathway and isoflurane-induced neuroapoptosis. The present study demonstrated
      that downregulation of the PI3K/Akt pathway reduced the effect of astaxanthin to
      protect against isoflurane-induced neuroapoptosis in the in vitro model. The
      results of the current study suggested that the protective effect of astaxanthin
      reduces the isoflurane-induced neuroapoptosis via activation of the PI3K/Akt
      signaling pathway. 

PMID- 27035666
TI  - The Central Role of Neuroscientists under National Socialism.
AB  - Neuroscientists played central roles in the victimization of colleagues and their
      patients during the era of National Socialism from 1933 to 1945. After helping
      dismiss Jewish and nonideologically aligned colleagues, German neuroscientists
      were among the physicians and researchers who joined the Nazi Party and
      affiliated groups in record numbers. Forced sterilization and then so-called
      'euthanasia' of neurological and psychiatric patients were planned and executed
      by prominent German and Austrian neuroscientists. Other neuroscientists
      collaborated indirectly by using patients for unethical experimentation to
      discover the cause of multiple sclerosis or to try to induce epileptic
      convulsions in a hypoxic state. Some merely used neuropathological material from
      murdered patients for publications in scientific journals. In the totalitarian
      state, research funding and academic advancement were awarded to physicians
      engaged in eugenics research. Opportunism and ideologically tainted science
      without regard to medical ethics were the motivating factors for collaborating
      neuroscientists. Some German and Austrian neuroscientists tried to resist Nazi
      policies, although much more passively than their colleagues in German-occupied
      countries. French, Dutch, Norwegian, and Danish neuroscientists actively resisted
      the Nazification of their profession from the beginning and helped to save some
      patients and colleagues, at great personal risk. Many German, Austrian, Czech,
      and Polish neurologists were murdered in the Holocaust, and hundreds of thousands
      of neurological and psychiatric patients were sterilized or murdered in just 12
      years. The Nazis used the 'successful' techniques developed in the 'euthanasia'
      programs to carry out the mass murder of millions in the Holocaust. Today's
      neuroscientists are obligated to learn of the ethical violations of their
      predecessors 70-80 years ago. No law will prevent abandonment of the basic
      principles of ethical patient care and professionalism that can occur in any
      totalitarian state, but neuroscientists can possibly prevent it. 

PMID- 27035667
TI  - Maximum Parsimony and the Skewness Test: A Simulation Study of the Limits of
      Applicability.
AB  - The maximum parsimony (MP) method for inferring phylogenies is widely used, but
      little is known about its limitations in non-asymptotic situations. This study
      employs large-scale computations with simulated phylogenetic data to estimate the
      probability that MP succeeds in finding the true phylogeny for up to twelve taxa
      and 256 characters. The set of candidate phylogenies are taken to be unrooted
      binary trees; for each simulated data set, the tree lengths of all (2n - 5)!!
      candidates are computed to evaluate quantities related to the performance of MP,
      such as the probability of finding the true phylogeny, the probability that the
      tree with the shortest length is unique, the probability that the true phylogeny
      has the shortest tree length, and the expected inverse of the number of trees
      sharing the shortest length. The tree length distributions are also used to
      evaluate and extend the skewness test of Hillis for distinguishing between random
      and phylogenetic data. The results indicate, for example, that the critical point
      after which MP achieves a success probability of at least 0.9 is roughly around
      128 characters. The skewness test is found to perform well on simulated data and
      the study extends its scope to up to twelve taxa. 

PMID- 27035668
TI  - Antibacterial Activity of Cold Atmospheric Pressure Argon Plasma against 78
      Genetically Different (mecA, luk-P, agr or Capsular Polysaccharide Type)
      Staphylococcus aureus Strains.
AB  - Previous studies on the antimicrobial activity of cold atmospheric pressure argon
      plasma showed varying effects against mecA+ or mecA-Staphylococcus aureus
      strains. This observation may have important clinical and epidemiological
      implications. Here, the antibacterial activity of argon plasma was investigated
      against 78 genetically different S. aureus strains, stratified by mecA, luk-P,
      agr1-4, or the cell wall capsule polysaccharide types 5 and 8. kINPen09(r) served
      as the plasma source for all experiments. On agar plates, mecA+luk-P-S. aureus
      strains showed a decreased susceptibility against plasma compared to other S.
      aureus strains. This study underlines the high complexity of microbial defence
      against antimicrobial treatment and confirms a previously reported strain
      dependent susceptibility of S. aureus to plasma treatment. 

PMID- 27035669
TI  - Combined Analysis of IFN-gamma, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT
      Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent
      Infection.
AB  - The QuantiFERON(r)-TB Gold In-Tube test (QFT), an interferon-gamma release assay,
      is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in
      distinguishing active tuberculosis from latent infection is a major concern.
      There is thus a need for an easy and accurate tool for achieving that goal in
      daily clinical settings. This study aimed to identify candidate cytokines for
      specifically differentiating active tuberculosis from latent infection. Our study
      population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent
      tuberculosis infection) patients and 10 healthy control subjects. We assayed for
      27 cytokines in QFT supernatants of both specific antigen-stimulated blood
      samples (TBAg) and negative-control samples (Nil). We analyzed their
      specificities and sensitivities by creating receiver operating characteristic
      (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil
      supernatants, IL-10, IFN-gamma, MCP-1 and IL-1RA showed high AUCs of 0.8120,
      0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone,
      combined assay for these top four cytokines showed positive rates in diagnosing
      active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in
      distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001).
      Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil
      supernatant levels are higher in LTBI compared to active TB, the difference
      between IFN-gamma and IL-2 showed a large AUC of 0.8910. In summary, besides IFN
      gamma, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for
      distinguishing active TB from LTBI. Those cytokines may also help us understand
      the difference in pathogenesis between active TB and LTBI. 

PMID- 27035670
TI  - The Promyelocytic Leukemia Zinc Finger Transcription Factor Is Critical for Human
      Endometrial Stromal Cell Decidualization.
AB  - Progesterone, via the progesterone receptor (PGR), is essential for endometrial
      stromal cell decidualization, a cellular transformation event in which stromal
      fibroblasts differentiate into decidual cells. Uterine decidualization supports
      embryo implantation and placentation as well as subsequent events, which together
      ensure a successful pregnancy. Accordingly, impaired decidualization results not
      only in implantation failure or early fetal miscarriage, but also may lead to
      potential adverse outcomes in all three pregnancy trimesters. Transcriptional
      reprogramming on a genome-wide scale underlies progesterone dependent
      decidualization of the human endometrial stromal cell (hESC). However,
      identification of the functionally essential signals encoded by these global
      transcriptional changes remains incomplete. Importantly, this knowledge-gap
      undercuts future efforts to improve diagnosis and treatment of implantation
      failure based on a dysfunctional endometrium. By integrating genome-wide datasets
      derived from decidualization of hESCs in culture, we reveal that the
      promyelocytic leukemia zinc finger (PLZF) transcription factor is rapidly induced
      by progesterone and that this induction is indispensable for progesterone
      dependent decidualization. Chromatin immunoprecipitation followed by next
      generation sequencing (ChIP-Seq) identified at least ten progesterone response
      elements within the PLZF gene, indicating that PLZF may act as a direct target of
      PGR signaling. The spatiotemporal expression profile for PLZF in both the human
      and mouse endometrium offers further support for stromal PLZF as a mediator of
      the progesterone decidual signal. To identify functional targets of PLZF,
      integration of PLZF ChIP-Seq and RNA Pol II RNA-Seq datasets revealed that the
      early growth response 1 (EGR1) transcription factor is a PLZF target for which
      its level of expression must be reduced to enable progesterone dependent hESC
      decidualization. Apart from furnishing essential insights into the molecular
      mechanisms by which progesterone drives hESC decidualization, our findings
      provide a new conceptual framework that could lead to new avenues for diagnosis
      and/or treatment of adverse reproductive outcomes associated with a dysfunctional
      uterus. 

PMID- 27035671
TI  - The Novel H7N9 Influenza A Virus NS1 Induces p53-Mediated Apoptosis of A549
      Cells.
AB  - BACKGROUND: H7N9, emerged as an avian influenza virus outbreak in Eastern China
      in early 2013, and represented another major threat to global health. Roles of
      its NS1 protein, an essential viral factor, in regulating apoptosis remain
      unknown. METHODS: Apoptotic effect and features of H7N9/NS1 in the human A549
      alveolar basal epithelial cell line were examined by caspase 3/7 activity assay
      and western blotting of apoptotic associated proteins. Effects of H7N9/NS1on
      mitochondrial membrane potential were investigated by flow cytometry. RESULTS:
      The expression of H7N9/NS1 in A549 cells activated caspase 3/7 and increased the
      protein levels of cleaved caspase 7 and cleaved poly (ADP-ribose) polymerase
      (PARP). H7N9/NS1-expressing A549 cells displayed a decrease in mitochondrial
      membrane potential. In addition, H7N9/NS1 increased the protein levels of total
      p53, p53 phosphorylated at Ser46 and Ser37, activated caspase 9, and the Bax/Bcl
      2 ratio. CONCLUSION: Our results suggest that H7N9/NS1 protein causes the
      accumulation of p53 by increasing phosphorylation levels of p53 and the induction
      of mitochondrial dysfunction, which may contribute to H7N9/NS1-induced apoptosis
      in A549 cells.

PMID- 27035672
TI  - Characterization of long non-coding RNA expression profiles in lymph node
      metastasis of early-stage cervical cancer.
AB  - Pelvic lymph node metastasis (PLNM) is an independent prognostic parameter and
      determines the treatment strategies of cervical cancer. Increasing evidence
      indicates that long non-coding RNAs (lncRNAs) play a crucial role in the process
      of tumor biological functions. This study aimed to mine lymph node metastasis
      associated lncRNAs and investigate their potential pathophysiological mechanism
      in cervical cancer lymph node metastasis. We applied the lncRNA-mining approach
      to identify lncRNA transcripts represented on Affymetrix human genome U133 plus
      2.0 microarrays from Gene Expression Omnibus (GEO) and then by validation in
      clinical specimens. The biological role and molecular mechanism of these lncRNAs
      were predicted by bioinformatic analysis. Subsequently, a receiver operating
      characteristic (ROC) curve and survival curve were conducted to evaluate the
      diagnostic and prognostic value of candidate lncRNAs. In total, 234
      differentially expressed lncRNAs were identified to significantly associate with
      pelvic lymph node metastasis in early-stage cervical cancer. Our qRT-PCR results
      were consistent with the mining analysis (P<0.05). The functional enrichment
      analysis suggested that these lncRNAs may be involved in the biological process
      of lymph node metastasis. The ROC curves demonstrated satisfactory discrimination
      power of MIR100HG and AC024560.2 with areas under the curve of 0.801 and 0.837,
      respectively. Survival curve also indicated that patients with high MIR100HG
      expression had a tendency of poor prognosis. This is the first study to
      successfully mine the lncRNA expression patterns in PLNM of early-stage cervical
      cancer. MIR100HG and AC024560.2 may be a potential biomarkers of PLNM and these
      lncRNAs may provide broader perspective for combating cervical cancer metastasis.

PMID- 27035673
TI  - Resveratrol attenuates inflammatory hyperalgesia by inhibiting glial activation
      in mice spinal cords.
AB  - The present study aimed to investigate the effect of resveratrol on inflammatory
      pain. Mice were injected intraperitoneally with lipopolysaccharide (LPS) for 5
      consecutive days to induce subacute systemic inflammation. Acetic acid-induced
      writhing tests and tail-flick tests were performed following the final LPS
      injection. Glial fibrillary acidic protein (GFAP; an astrocyte-specific
      activation marker), ionized calcium binding adapter molecule 1 (Iba-1; a
      microglia-specific activation marker) and sirtuin 1 (SIRT1) protein expression
      levels were detected using immunohistochemistry analysis or western blotting.
      Following administration of LPS for 5 days, the number of writhes increased and
      the tail-flick latency decreased. Resveratrol (10 or 20 mg/kg) partly inhibited
      LPS-induced hyperalgesia and prevented the increase in tumor necrosis factor
      alpha and interleukin 6 levels induced by LPS. LPS injection reduced the SIRT1
      protein expression and increased the number of GFAP-positive and Iba-1-positive
      cells in the spinal cord. Resveratrol increased the SIRT1 protein expression
      levels and decreased the number of GFAP-positive and Iba-1-positive cells in LPS
      treated mice. The protective effect of resveratrol was partly blocked by a
      selective SIRT1 inhibitor, EX-257. Results from the present study suggest that
      subacute treatment with LPS induced the activation of glial cells and
      hyperalgesia. Resveratrol was demonstrated to inhibit the activation of glial
      cells and attenuate inflammatory hyperalgesia in a SIRT1-dependent manner. 

PMID- 27035674
TI  - Patterns of oral disease in adults with chronic kidney disease treated with
      hemodialysis.
AB  - BACKGROUND: Oral disease is a potentially treatable determinant of mortality and
      quality of life. No comprehensive multinational study to quantify oral disease
      burden and to identify candidate preventative strategies has been performed in
      the dialysis setting. METHODS: The ORAL disease in hemoDialysis (ORALD) study was
      a prospective study in adults treated with hemodialysis in Europe (France,
      Hungary, Italy, Poland, Portugal and Spain) and Argentina. Oral disease was
      assessed using standardized WHO methods. Participants self-reported oral health
      practices and symptoms. Sociodemographic and clinical factors associated with
      oral diseases were determined and assessed within nation states. RESULTS: Of 4726
      eligible adults, 4205 (88.9%) participated. Overall, 20.6% were edentulous [95%
      confidence interval (CI), 19.4-21.8]. Participants had on average 22 (95% CI 21.7
      22.2) decayed, missing or filled teeth, while moderate to severe periodontitis
      affected 40.6% (95% CI 38.9-42.3). Oral disease patterns varied markedly across
      countries, independent of participant demographics, comorbidity and health
      practices. Participants in Spain, Poland, Italy and Hungary had the highest mean
      adjusted odds of edentulousness (2.31, 1.90, 1.90 and 1.54, respectively), while
      those in Poland, Hungary, Spain and Argentina had the highest odds of >=14
      decayed, missing or filled teeth (23.2, 12.5, 8.14 and 5.23, respectively).
      Compared with Argentina, adjusted odds ratios for periodontitis were 58.8, 58.3,
      27.7, 12.1 and 6.30 for Portugal, Italy, Hungary, France and Poland,
      respectively. National levels of tobacco consumption, diabetes and child poverty
      were associated with edentulousness within countries. CONCLUSIONS: Oral disease
      in adults on hemodialysis is very common, frequently severe and highly variable
      among countries, with much of the variability unexplained by participant
      characteristics or healthcare. Given the national variation and high burden of
      disease, strategies to improve oral health in hemodialysis patients will require
      implementation at a country level rather than at the level of individuals.

PMID- 27035675
TI  - Neurology and War: From Antiquity to Modern Times.
AB  - Here, we chronicle the evolution of warfare from antiquity to modern times (18th
      century) and its impact on the later-to-be-defined field of neurology, especially
      with regard to brain, spinal cord and peripheral nerve injuries and neurological
      disorders caused by biological weapons and psychological trauma. We describe how
      individuals courageously and intelligently dealt with the horrors of war, from
      the Egyptians to the Greeks and onward to the Romans, up until the physicians of
      modern times. In doing so, they responded to the call of duty by inventing
      solutions that benefitted not only soldiers but also civilian medicine. 

PMID- 27035676
TI  - Silas Weir Mitchell: Neurologists and Neurology during the American Civil War.
AB  - With few exceptions, neurology was nonexistent in the United States until the
      Civil War years. From 1861 to 1865, the United States saw a bitter armed conflict
      between the North (the Union) and the South (the Confederate States or
      Confederacy), and during those years, neurology was born in the United States. In
      1861, Silas Weir Mitchell, together with George Morehouse and William Keen,
      opened and operated the first neurological hospital in Philadelphia, with the
      backing of the Surgeon General William Hammond. They treated and studied many
      peripheral nerve diseases, which led to their making the medical world aware of
      several conditions, including causalgia (now known as complex regional pain
      syndrome) and the phantom limb phenomenon. Progress in neurology, both at that
      time and in subsequent years, owed a great deal to cross-fertilization from
      Europe. Charles Edouard Brown-Sequard exemplified this. He held multiple medical
      positions on both sides of the Atlantic, including a position at Harvard in 1864.
      His teachings, to some extent, contributed to the development of neurology in the
      United States. In the Confederate states, medical care was less well organized,
      and neurology only developed later. After the war, in 1874, Mitchell, Hammond,
      and a few others founded the American Neurological Association. While war
      influenced the development of medicine, and neurology in particular, medicine
      also helped to shape the outcome of the war. 

PMID- 27035677
TI  - Hormone signaling pathways as treatment targets in renal cell cancer (Review).
AB  - Epidemiological, clinical, biochemical and genetic research has revealed that
      renal cell cancer (RCC) etiology is hormone-related. It was shown that hormone
      receptors are abnormally expressed in RCC cells. Abnormal endocrine stimulation
      also plays a significant role in RCC pathophysiology. Cellular proliferation,
      migration, angiogenesis, and drug resistance in RCC is modulated by para- and
      autocrine hormonal stimulation. In particular, RCC overexpression of gonadotropin
      releasing hormone and its receptor was reported. On the contrary, corticotropin
      releasing hormone was reported to inhibit RCC cell proliferation and regulate
      angiogenesis. Overexpression of luteinizing hormone also promotes RCC tumor
      angiogenesis. Estrogen receptor alpha overexpression increases the
      transcriptional factor activity of hypoxia inducible factor HIF-1alpha, but
      estrogen receptor beta has a cancer suppressive role. Glucocorticoid receptors
      and androgen receptor are markers of indolent RCC and assigned tumor suppressive
      activity. Proopiomelanocortin is upregulated in VHL-mutated renal cell carcinoma
      via Nur77 transcription factor signaling. In RCC, follicle-stimulating hormone
      receptor promotes angiogenesis and metastatic formation via VEGF release.
      Mineralocorticoid receptor overexpression promotes cell survival and increases
      RCC cell proliferation. Vitamin D receptor expression is downregulated or absent
      in RCC and differentiate subtypes of renal cell tumors. RAR-beta promotes
      tumorigenesis but retinoic acid receptor gamma expression correlates negatively
      with the TNM stage at diagnosis. Finally, progesterone receptor expression is
      negatively correlated with the cancer stage. Molecular data analysis revealed the
      possibility of renal cancer cell proliferation induction via hormone activated
      pathways. Inhibition of hormonal signaling may thus play a putative role in
      supportive therapies against this cancer type. 

PMID- 27035678
TI  - Evaluation of a cross contamination model describing transfer of Salmonella spp.
      and Listeria monocytogenes during grinding of pork and beef.
AB  - In a previous study, a model was developed to describe the transfer and survival
      of Salmonella during grinding of pork (Moller, C.O.A., Nauta, M.J., Christensen,
      B.B., Dalgaard, P., Hansen, T.B., 2012. Modelling transfer of Salmonella
      typhimurium DT104 during simulation of grinding of pork. Journal of Applied
      Microbiology 112 (1), 90-98). The robustness of this model is now evaluated by
      studying its performance for predicting the transfer and survival of Salmonella
      spp. and Listeria monocytogenes during grinding of different types of meat (pork
      and beef), using two different grinders, different sizes and different numbers of
      pieces of meats to be ground. A total of 19 grinding trials were collected.
      Acceptable Simulation Zone (ASZ), visual inspection of the data, Quantitative
      Microbiological Risk Assessment (QMRA), as well as the Total Transfer Potential
      (TTP) were used as approaches to evaluate model performance and to access the
      quality of the cross contamination model predictions. Using the ASZ approach and
      considering that 70% of the observed counts have to be inside a defined
      acceptable zone of +/-0.5 log10CFU per portion, it was found that the cross
      contamination parameters suggested by Moller et al. (2012) were not able to
      describe all 19 trials. However, for each of the collected grinding trials, the
      transfer event was well described when fitted to the model structure proposed by
      Moller et al. (2012). Parameter estimates obtained by fitting observed trials
      performed at different conditions, such as size and number of pieces of meat to
      be ground, may not be applied to describe cross contamination of unlike
      processing. Nevertheless, the risk estimates, as well as the TTP, revealed that
      the risk of disease may be reduced when the grinding of meat is performed in a
      grinder made of stainless steel (for all surfaces in contact with the meat),
      using a well-sharpened knife and holding at room temperatures lower than 4
      degrees C. 

PMID- 27035679
TI  - Neutrophil elastase enhances the proliferation and decreases apoptosis of
      leukemia cells via activation of PI3K/Akt signaling.
AB  - Neutrophil elastase (NE) is a neutrophil-derived serine proteinase with
      specificity for a broad range of substrates. NE has been reported to be
      associated with the pathogenesis of several conditions, particularly that of
      pulmonary diseases. Previous studies have shown that NE can cleave the pro
      myelocyte - retinoic acid receptor-alpha chimeric protein and is important for
      the development of acute pro-myelocytic leukemia. To further elucidate the role
      of NE in acute pro-myelocytic leukemia, the present study successfully
      constructed a lentiviral vector containing the NE gene (LV5-NE), which was
      transfected into NB4 acute pro-myelocytic leukemia cells. The effects of NE
      overexpression in NB4 cells were detected using a Cell-Counting Kit-8 assay, flow
      cytometry and western blot analysis. The results showed that NE significantly
      promoted the proliferation of NB4 cells, inhibited cell apoptosis and apoptotic
      signaling, and led the activation of Akt. In an additional experiment, a vector
      expressing small hairpin RNA targeting NE was constructed to assess the effects
      of NE knockdown in U937 cells. Western blot analysis revealed that apoptotic
      signaling was increased, while Akt activation was decreased following silencing
      of NE. The results of the present study may indicate that NE activates the
      phosphoinositide-3 kinase/Akt signaling pathway in leukemia cells to inhibit
      apoptosis and enhance cell proliferation, and may therefore represent a molecular
      target for the treatment of pro-myelocytic leukemia. 

PMID- 27035680
TI  - Upregulation of long non coding RNA PCAT-1 contributes to cell proliferation,
      migration and apoptosis in hepatocellular carcinoma.
AB  - Long non-coding RNAs (lncRNAs) exert regulatory functions on various biological
      processes in cancer cells, including proliferation, apoptosis and mobility.
      Prostate cancer-associated transcript 1 (PCAT-1) is a novel lncRNA that promotes
      cell proliferation in prostate cancer, however, the effect of PCAT-1 in
      hepatocellular carcinoma (HCC) remains to be elucidated. The present study
      hypothesized that PCAT-1 also exerts an important effect in HCC. The current
      study investigated PCAT-1 expression levels in HCC tissue samples and HepG2 and
      Bel-7402 cell lines using the reverse transcription-quantitative polymerase chain
      reaction. The results demonstrated that PCAT-1 was upregulated in HCC tissue
      samples and cell lines compared with adjacent non-cancerous tissues and the L02
      normal liver epithelial cell line. PCAT-1 suppression using PCAT-1 small hairpin
      RNA in HepG2 and Bel-7402 cells inhibited cell proliferation and migration, and
      induced apoptosis. Overexpression of PCAT-1 induced synthetic plasmid vectors was
      demonstrated to increase cell proliferation and migration, and inhibit apoptosis.
      Results from the present study suggest that PCAT-1 exerts an oncogenic effect in
      HCC and silencing PCAT-1 may be a potential novel therapeutic strategy for HCC. 

PMID- 27035681
TI  - Retraction: "The Role of the Extracellular Matrix Protein Mindin in Airway
      Response to Environmental Airways Injury".

PMID- 27035682
TI  - Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2
      plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and
      bone regeneration.
AB  - The recent development of bioactive glasses with nanoscale morphologies has
      spurred their specific applications in bone regeneration, for example as drug and
      gene delivery carriers. Bone engineering with stem cells genetically modified
      with this unique class of nanocarriers thus holds great promise in this avenue.
      Here we report the potential of the bioactive glass nanoparticle (BGN) system for
      the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The
      composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated
      into surface aminated mesoporous nanospheres with enlarged pore sizes, to
      effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The
      enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency
      as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small
      sized mesopores. The BGN nanocarriers released the genetic molecules in a highly
      sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were
      effectively internalized to rat MSCs with a cell uptake level of ~73%, and the
      majority of cells were transfected to express the BMP2 protein. Subsequent
      osteogenesis of the transfected MSCs was demonstrated by the expression of bone
      related genes, including bone sialoprotein, osteopontin, and osteocalcin. The
      MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel
      to the target calvarium defects. The results showed significantly improved bone
      regeneration, as evidenced by the micro-computed tomographic, histomorphometric
      and immunohistochemical analyses. This study supports the excellent capacity of
      the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system,
      BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance
      the therapeutic potential of stem cells through genetic modification, targeting
      bone defects and diseases. 

PMID- 27035683
TI  - Proteomics analysis reveals distinct involvement of embryo and endosperm proteins
      during seed germination in dormant and non-dormant rice seeds.
AB  - Seed germination is a complex trait which is influenced by many genetic,
      endogenous and environmental factors, but the key event(s) associated with seed
      germination are still poorly understood. In present study, the non-dormant
      cultivated rice Yannong S and the dormant Dongxiang wild rice seeds were used as
      experimental materials, we comparatively investigated the water uptake,
      germination time course, and the differential proteome of the effect of embryo
      and endosperm on germination of these two types of seeds. A total of 231 and 180
      protein spots in embryo and endosperm, respectively, showed a significant change
      in abundance during germination. We observed that the important proteins
      associated with seed germination included those involved in metabolism, energy
      production, protein synthesis and destination, storage protein, cell growth and
      division, signal transduction, cell defense and rescue. The contribution of
      embryo and endosperm to seed germination is different. In embryo, the proteins
      involved in amino acid activation, sucrose cleavage, glycolysis, fermentation and
      protein synthesis increased; in endosperm, the proteins involved in sucrose
      cleavage and glycolysis decreased, and those with ATP and CoQ synthesis and
      proteolysis increased. Our results provide some new knowledge to understand
      further the mechanism of seed germination. 

PMID- 27035684
TI  - Measurements of Submicron Particle Adsorption and Particle Film Elasticity at Oil
      Water Interfaces.
AB  - The influence of particle adsorption on liquid/liquid interfacial tension is not
      well understood, and much previous research has suggested conflicting behaviors.
      In this paper we investigate the surface activity and adsorption kinetics of
      charge stabilized and pH-responsive polymer stabilized colloids at oil/water
      interfaces using two tensiometry techniques: (i) pendant drop and (ii)
      microtensiometer. We found, using both techniques, that charge stabilized
      particles had little or no influence on the (dynamic) interfacial tension,
      although dense silica particles affected the "apparent" measured tension in the
      pendent drop, due to gravity driven elongation of the droplet profile.
      Nevertheless, this apparent change additionally allowed the study of adsorption
      kinetics, which was related qualitatively between particle systems by estimated
      diffusion coefficients. Significant and real interfacial tension responses were
      measured using ~53 nm core-shell latex particles with a pH-responsive polymer
      stabilizer of poly(methyl methacrylate)-b-poly(2-(dimethylamino)ethyl
      methacrylate) (pMMA-b-pDMAEMA) diblock copolymer. At pH 2, where the polymer is
      strongly charged, behavior was similar to that of the bare charge-stabilized
      particles, showing little change in the interfacial tension. At pH 10, where the
      polymer is discharged and poorly soluble in water, a significant decrease in the
      measured interfacial tension commensurate with strong adsorption at the oil-water
      interface was seen, which was similar in magnitude to the surface activity of the
      free polymer. These results were both confirmed through droplet profile and
      microtensiometry experiments. Dilational elasticity measurements were also
      performed by oscillation of the droplet; again, changes in interfacial tension
      with droplet oscillation were only seen with the responsive particles at pH 10.
      Frequency sweeps were performed to ascertain the dilational elasticity modulus,
      with measured values being significantly higher than previously reported for
      nanoparticle and surfactant systems, and similar in magnitude to protein
      stabilized droplets.

PMID- 27035685
TI  - Sonoelastography in the Evaluation of Plantar Fasciitis Treatment: 3-Month Follow
      Up After Collagen Injection.
AB  - OBJECTIVE: The aim of this study was to investigate whether ultrasound
      elastography can demonstrate the outcome of the treatment in comparison with gray
      scale imaging. METHODS: Sixteen patients (mean age, 46.9 years) with plantar
      fasciitis were prospectively enrolled after unsuccessful conservative treatment.
      Individuals graded their heel pain on a 100-mm visual analogue scale (VAS) and
      underwent gray-scale ultrasonography and sonoelastography. Collagen was injected
      in the heels. Fascial thickness and hypoechogenicity, perifascial edema, and
      plantar fascial elasticity were evaluated. Follow-up sonoelastography and VAS
      grading were done 3 months after the injection. Statistical analyses were
      performed by the paired t test and the Fisher exact test. A P < 0.05 was
      considered statistically significant. RESULTS: Mean plantar fascial thickness
      showed insignificant decrease on follow-up (from 4.30 [1.37] to 4.23 [1.15] mm, P
      = 0.662). Fascial hypoechogenicity and perifascial edema did not change
      significantly after treatment. The mean strain ratio of the plantar fascia was
      significantly increased (from 0.71 [0.24] to 1.66 [0.72], P = 0.001). Softening
      of the plantar fascia decreased significantly after injection (from 12 to 3 ft, P
      = 0.004). Twelve (75%) of 16 patients showed significant VAS improvement at the
      follow-up. CONCLUSIONS: Sonoelastography revealed a hardening of the plantar
      fascia after collagen injection treatment and could aid in monitoring the
      improvement of the symptoms of plantar fasciitis, in cases where gray-scale
      imaging is inconclusive.

PMID- 27035686
TI  - Commentary: Screening for Thyroid Cancer After the Fukushima Disaster: What Do We
      Learn From Such an Effort?

PMID- 27035687
TI  - Commentary: On the Use of Imperfect Negative Control Exposures in Epidemiologic
      Studies.

PMID- 27035688
TI  - Within-subject Pooling of Biological Samples to Reduce Exposure Misclassification
      in Biomarker-based Studies.
AB  - BACKGROUND: For chemicals with high within-subject temporal variability,
      assessing exposure biomarkers in a spot biospecimen poorly estimates average
      levels over long periods. The objective is to characterize the ability of within
      subject pooling of biospecimens to reduce bias due to exposure misclassification
      when within-subject variability in biomarker concentrations is high. METHODS: We
      considered chemicals with intraclass correlation coefficients of 0.6 and 0.2. In
      a simulation study, we hypothesized that the chemical urinary concentrations
      averaged over a given time period were associated with a health outcome and
      estimated the bias of studies assessing exposure that collected 1 to 50 random
      biospecimens per subject. We assumed a classical type error. We studied
      associations using a within-subject pooling approach and two measurement error
      models (simulation extrapolation and regression calibration), the latter
      requiring the assay of more than one biospecimen per subject. RESULTS: For both
      continuous and binary outcomes, using one sample led to attenuation bias of 40%
      and 80% for compounds with intraclass correlation coefficients of 0.6 and 0.2,
      respectively. For a compound with an intraclass correlation coefficient of 0.6,
      the numbers of biospecimens required to limit bias to less than 10% were 6, 2,
      and 2 biospecimens with the pooling, simulation extrapolation, and regression
      calibration methods (these values were, respectively, 35, 8, and 2 for a compound
      with an intraclass correlation coefficient of 0.2). Compared with pooling, these
      methods did not improve power. CONCLUSION: Within-subject pooling limits
      attenuation bias without increasing assay costs. Simulation extrapolation and
      regression calibration further limit bias, compared with the pooling approach,
      but increase assay costs.

PMID- 27035689
TI  - Brief Report: Staged-informed Consent in the Cohort Multiple Randomized
      Controlled Trial Design.
AB  - The "cohort multiple randomized controlled trial," a new design for pragmatic
      trials, embeds multiple trials within a cohort. The cohort multiple RCT is an
      attractive alternative to conventional RCTs in fields where recruitment is slow,
      multiple new (competing) interventions for the same condition have to be tested,
      new interventions are highly preferred by patients and doctors, and the risk of
      disappointment bias, cross-over, and contamination is considerable. To prevent
      these unwanted effects, the cohort multiple RCT provides information on
      randomization to the intervention group/arm only, and only after randomization
      (i.e., prerandomization). To some, especially in a clinical setting, this is not
      ethically acceptable. In this article, we argue that prerandomization in the
      cohort multiple randomized controlled trial (cmRCT) can be avoided by adopting a
      staged-informed consent procedure. In the first stage, at entry into the cohort,
      all potential participants are asked for their informed consent to participate in
      a cohort study and broad consent to be either randomly selected to be approached
      for experimental interventions or to serve as control without further notice
      during participation in the cohort. In a second stage, at the initiation of an
      RCT within the cohort, informed consent to receive the intervention is then only
      sought in those randomly selected for the intervention arm. At the third stage,
      after completion of each RCT, all cohort participants receive aggregate
      disclosure of trial results. This staged-informed consent procedure avoids
      prerandomization in cmRCT and aims to keep participants actively engaged in the
      research process. 

PMID- 27035690
TI  - Long-term Coarse Particulate Matter Exposure and Heart Rate Variability in the
      Multi-ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Reduced heart rate variability, a marker of impaired cardiac
      autonomic function, has been linked to short-term exposure to airborne particles.
      This research adds to the literature by examining associations with long-term
      exposures to coarse particles (PM10-2.5). METHODS: Using electrocardiogram
      recordings from 2,780 participants (45-84 years) from three Multi-ethnic Study of
      Atherosclerosis sites, we assessed the standard deviation of normal to normal
      intervals and root-mean square differences of successive normal to normal
      intervals at a baseline (2000-2002) and follow-up (2010-2012) examination (mean
      visits/person = 1.5). Annual average concentrations of PM10-2.5 mass, copper,
      zinc, phosphorus, silicon, and endotoxin were estimated using site-specific
      spatial prediction models. We assessed associations for baseline heart rate
      variability and rate of change in heart rate variability over time using
      multivariable mixed models adjusted for time, sociodemographic, lifestyle,
      health, and neighborhood confounders, including copollutants. RESULTS: In our
      primary models adjusted for demographic and lifestyle factors and site, PM10-2.5
      mass was associated with 1.0% (95% confidence interval [CI]: -4.1, 2.1%) lower
      standard deviation of normal to normal interval levels per interquartile range of
      2 MUg/m. Stronger associations, however, were observed before site adjustment and
      with increasing residential stability. Similar patterns were found for root-mean
      square differences of successive normal to normal intervals. We found little
      evidence for associations with other chemical species and with the rate of change
      in heart rate variability, though endotoxin was associated with increasing heart
      rate variability over time. CONCLUSION: We found only weak evidence that long
      term PM10-2.5 exposures are associated with lowered heart rate variability.
      Stronger associations among residentially stable individuals suggest that
      confirmatory studies are needed.

PMID- 27035691
TI  - Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell
      effector functions.
AB  - The folate receptor (FR) is overexpressed on the vascular side of cancerous cells
      including those of the breast, ovaries, testes, and cervix. We hypothesized that
      a folate-conjugated immunoglobulin (F-IgG) would bind to the FR that is
      overexpressed on melanoma tumor cells to target these cells for lysis by natural
      killer (NK) cells. Folate receptor expression was confirmed in the Mel-39 (human
      melanoma) cell line by flow cytometry and immunoblot analysis using KB (human
      oral epithelial) and F01 (human melanoma) as a positive and a negative control,
      respectively. FR-positive and FR-negative cell lines were treated with F-IgG or
      control immunoglobulin G in the presence or absence of cytokines to determine NK
      cell ability to lyse FR-positive cell lines. NK cell activation was significantly
      upregulated and lysis of Mel 39 tumor cells increased following treatment with F
      IgG compared with control immunoglobulin G at all effector : target (E : T)
      ratios (P<0.01). This trend further increased by NK cell stimulation with the
      activating cytokine interleukin-12. NK cell production of cytokines such as
      interferon-gamma, macrophage inflammatory protein 1alpha, and regulated on
      activation normal T-cell expressed and secreted (RANTES) was also significantly
      increased in response to costimulation with interleukin-12 stimulation and F-IgG
      coated Mel 39 target cells compared with controls (P<0.01). In contrast, F-IgG
      did not bind to the FR-negative cell line F01 and had no significant effect on NK
      cell lysis or cytokine production. This research indicates the potential use of F
      IgG for its ability to induce an immune response from NK cells against FR
      positive melanoma tumor cells, which can be further increased by the addition of
      cytokines.

PMID- 27035692
TI  - Same-Sex and Different-Sex Parent Households and Child Health Outcomes: Findings
      from the National Survey of Children's Health.
AB  - OBJECTIVE: Using the 2011-2012 National Survey of Children's Health data set, we
      compared spouse/partner relationships and parent-child relationships (family
      relationships), parenting stress, and children's general health, emotional
      difficulties, coping behavior, and learning behavior (child outcomes) in
      households of same-sex (female) versus different-sex continuously coupled parents
      with biological offspring. We assessed whether associations among family
      relationships, parenting stress, and child outcomes were different in the 2
      household types. METHODS: Parental and child characteristics were matched for 95
      female same-sex parent and 95 different-sex parent households with children 6 to
      17 years old. One parent per household was interviewed by telephone. Multivariate
      analyses of variance and multiple linear regressions were conducted. RESULTS: No
      differences were observed between household types on family relationships or any
      child outcomes. Same-sex parent households scored higher on parenting stress (95%
      confidence interval = 2.03-2.30) than different-sex parent households (95%
      confidence interval = 1.76-2.03), p = .006. No significant interactions between
      household type and family relationships or household type and parenting stress
      were found for any child outcomes. CONCLUSION: Children with female same-sex
      parents and different-sex parents demonstrated no differences in outcomes,
      despite female same-sex parents reporting more parenting stress. Future studies
      may reveal the sources of this parenting stress.

PMID- 27035693
TI  - Provider Communication Regarding Psychosocial Factors Predicts Pain Beliefs in
      Parent and Child.
AB  - OBJECTIVE: To examine the role of provider communication about psychosocial
      causes of abdominal pain and recommendations for psychosocial intervention during
      a gastroenterology clinic visit in predicting families' causal beliefs and
      perceptions of treatment acceptability. METHOD: Participants were 57 children
      with a diagnosed or suspected abdominal pain-related functional gastrointestinal
      disorder (FGID) presenting for an outpatient gastroenterology follow-up visit and
      their accompanying parent. Children and parents completed questionnaires
      assessing child anxiety and abdominal pain severity, recall of provider
      communication about causes of abdominal pain and recommendations for
      intervention, their own causal beliefs about pain, and perceived acceptability of
      cognitive behavioral therapy (CBT) and standard medical treatment (SMT) after
      reading descriptions of each treatment. Providers completed a questionnaire
      assessing their perceptions and communication about the causes of the child's
      abdominal pain and perceived acceptability of CBT. RESULTS: Provider
      communication about psychosocial causes and interventions was reported
      infrequently by parents, children, and providers. Parents rated psychosocial
      causes for abdominal pain as less likely than physical causes, and children and
      parents rated CBT as less acceptable than SMT. Parents' recall of provider
      communication about psychosocial causes was associated with their own causal
      beliefs about pain and their perceived acceptability of CBT. Children's and
      parents' recall of provider recommendations for psychosocial intervention was
      associated with their perceived acceptability of CBT. CONCLUSION: Results
      highlight the importance of provider communication about psychosocial
      contributors to abdominal pain and psychosocial interventions for children with
      FGIDs. Medical and mental health providers can partner to deliver care to
      children with FGIDs using a biopsychosocial approach.

PMID- 27035695
TI  - Moving Beyond Anti-LGBT Politics: Commentary on "Same-Sex and Different-Sex
      Parent Households and Child Health Outcomes: Findings from the National Survey of
      Children's Health".

PMID- 27035696
TI  - Household Income and Child Behavior: Turn Up the Power and Add New Elements to
      View.

PMID- 27035697
TI  - Mathematics Awareness Month: Why Should Pediatricians be Aware of Mathematics and
      Numeracy?

PMID- 27035694
TI  - Low Family Income and Behavior Problems in Norwegian Preschoolers: Is Child
      Emotionality a Marker for Sensitivity of Influence?
AB  - Poor children have higher rates of mental health problems than more affluent
      peers, also in progressive welfare states such as Norway. Temperamental
      characteristics may render some children more sensitive to the adverse influence
      of poor economy. OBJECTIVE: This study examined the direct associations between
      family income-to-needs and mental health and assessed moderation by early
      temperamental characteristics (i.e., emotionality). METHOD: Using data from the
      Norwegian Mother and Child Cohort Study, associations between income-to-needs
      across children's first 3 years and internalizing and externalizing problems when
      children were 5 years old were examined. Differential sensitivity to family
      income-to-needs was assessed by investigating how emotionality, when children
      were one-and-a-half and 3 years old, moderated these associations. RESULTS:
      Significant main effects of income-to-needs and emotionality and a significant
      interaction effect between income-to-needs and emotionality were found for
      externalizing problems, but not for internalizing problems. CONCLUSION: Children
      in poor families with an emotionally reactive temperament had higher scores on
      externalizing problems when they were 5 compared with their less emotionally
      reactive peers.

PMID- 27035698
TI  - Attention-Deficit/Hyperactivity Disorder, Behavior Regulation and Virtual School
      Support.
AB  - CASE: Tony is a 6-year-old multiracial boy diagnosed as having attention
      deficit/hyperactivity disorder-combined type who is followed in your primary care
      practice and has started on a stimulant medication. Tony continues to have
      difficulty with emotion regulation and impulse control both at home and at
      school. He was asked to leave his private school soon after beginning first grade
      because of physical fighting, emotional outbursts, and arguing with teachers.His
      mother made the decision to enroll Tony in online virtual schooling for the
      remainder of the academic year, with the plan to transition back to traditional
      school for the next academic year. They have enrolled in a program that offers
      lessons online and sends materials to the home for the child to use to complete
      certain types of assignments (e.g., science experiments). Virtual schools are
      different from traditional home schooling because children receive their
      instruction from teachers online with parental assistance as opposed to parents
      being responsible for teaching all material. Tony's mother comes to your practice
      requesting assistance with setting up an appropriate school environment for her
      son at home, where she can monitor and support his academic progress.Tony is a
      bright child, with an Intelligence Quotient in the superior range. He has
      advanced academic skills, but he becomes dysregulated if he is told he is wrong
      or that he has answered a question incorrectly. For example, if he answered a
      question incorrectly in class, he would become verbally abusive toward his
      teacher and often have temper tantrums. This challenging behavior occurred daily
      at school and was one of the factors leading to his expulsion. The behavior had
      predated the introduction of stimulant medication and had remained consistent
      after he began medication.Tony's parents are highly educated, and both parents
      hold professional jobs with steady income. His parents have good command of
      typical behavior management strategies such as the use of rewards, time out, and
      behavioral contingencies to target noncompliance and temper tantrums. However,
      Tony's difficulty identifying and regulating his emotions leads to emotional
      outbursts and shutdowns that have thus far been unresponsive to standard behavior
      management techniques. Tony continued to have outbursts even when the behavior
      was ignored. His mother is concerned not only about his learning during the
      coming year but also about his social relationships and the family dynamic.
      Tony's outbursts cause significant disruption in the home and are a source of
      tension among parents and siblings.His mother is asking for advice on how to
      support his behavior better at home now that he will be spending his entire day
      there. How might you assist this child and his mother by helping to integrate
      therapeutic goals into the academic environment?

PMID- 27035699
TI  - Mirrored and rotated stimuli are not the same: A neuropsychological and lesion
      mapping study.
AB  - Agnosia for mirrored stimuli is a rare clinical deficit. Only eight patients have
      been reported in the literature so far and little is known about the neural
      substrates of this agnosia. Using a previously developed experimental test
      designed to assess this agnosia, namely the Mirror and Orientation Agnosia Test
      (MOAT), as well as voxel-lesion symptom mapping (VLSM), we tested the hypothesis
      that focal brain-injured patients with right parietal damage would be impaired in
      the discrimination between the canonical view of a visual object and its mirrored
      and rotated images. Thirty-four consecutively recruited patients with a stroke
      involving the right or left parietal lobe have been included: twenty patients
      (59%) had a deficit on at least one of the six conditions of the MOAT, fourteen
      patients (41%) had a deficit on the mirror condition, twelve patients (35%) had a
      deficit on at least one the four rotated conditions and one had a truly selective
      agnosia for mirrored stimuli. A lesion analysis showed that discrimination of
      mirrored stimuli was correlated to the mesial part of the posterior superior
      temporal gyrus and the lateral part of the inferior parietal lobule, while
      discrimination of rotated stimuli was correlated to the lateral part of the
      posterior superior temporal gyrus and the mesial part of the inferior parietal
      lobule, with only a small overlap between the two. These data suggest that the
      right visual 'dorsal' pathway is essential for accurate perception of mirrored
      and rotated stimuli, with a selective cognitive process and anatomical network
      underlying our ability to discriminate between mirrored images, different from
      the process of discriminating between rotated images.

PMID- 27035700
TI  - Contralesional distractors enhance ipsilesional target processing after right
      hemispheric stroke.
AB  - Stroke can result in marked impairments in the processing of information
      presented in contralesional space. The present prospective study investigated how
      a contralesional distractor affects ipsilesional perception in patients with a
      right-hemispheric stroke. In a simple target detection task, the influence of the
      distractor on reaction times (RTs) was examined in stroke patients and compared
      to the performance of healthy elderly controls. Distractor interference effects
      were related to measures of neglect and extinction using a regression analysis.
      Moreover, the magnitude of the behavioural distractor effect entered a voxel
      based lesion-symptom mapping (VLSM) analysis with the hypothesis that parietal
      and temporoparietal lesions are related to altered distractor processing. While
      the presence of a distractor in the opposite hemifield slowed down RTs in healthy
      controls for left and right targets, this effect was only observed for
      contralesional left targets in the group of right-hemispheric patients. In stark
      contrast, the presence of a distractor in the contralesional hemifield expedited
      ipsilesional (i.e., right) target detection. This effect was significantly
      related to lesions in the anterior middle temporal and temporoparietal cortex,
      external and internal capsule, as well as the superior longitudinal fascicle
      (SLF). These results elucidate the nature of the disruption of attentive
      processing in the contralesional hemifield after right-hemispheric stroke. More
      specifically, they shed light on the abnormal prioritisation of ipsilesional
      information: our data suggest that damage to the temporal and temporoparietal
      cortex and white matter tracts may transform contralesional stimulation into an
      unspecific saliency signal contributing to facilitated information processing in
      ipsilesional space.

PMID- 27035701
TI  - History of postpartum depression in a clinic-based sample of women with
      premenstrual dysphoric disorder.
AB  - OBJECTIVE: Overlapping comorbidities between premenstrual dysphoric disorder
      (PMDD) and postpartum depression (PPD) suggest that these disorders represent a
      continuum of vulnerability with shared pathophysiology. We report the past
      histories of PPD (and other Axis I psychiatric illnesses) in a clinic-based
      sample of women meeting criteria for PMDD. METHODS: 215 women, ages 19 to 51
      years, who attended the National Institute of Mental Health Mood Disorders Clinic
      between 1988 and 2013 seeking treatment for PMDD and in whom we confirmed the
      diagnosis of PMDD (DSM-IV), were identified. All were administered the Structured
      Clinical Interview for DSM-III-R or -IV. The frequency of PPD (major or minor)
      was established in the subgroup of women (n = 137) who had delivered at least 1
      child. RESULTS: Ninety-three women (43.3%) had a past history of a mood disorder
      (ie, either major [n = 67; 31.2%] or minor [n = 10; 4.7%] depression or PPD [n =
      16; 7.4%; 11.7% of parous women]). Nine of the 16 women with PMDD and a past PPD
      had either a past major depressive episode (MDE) or subsyndromal anxiety
      disorder. Thirty-three women (15.3%) had a past history of an Axis I anxiety
      disorder. A total of 40 women (18.6%) met criteria for past alcohol or drug
      abuse, 3 (1.4%) met criteria for bulimia nervosa, and 2 (0.9%) met criteria for
      anorexia nervosa. CONCLUSIONS: Our data demonstrate that PMDD and PPD do not
      frequently co-occur. These data do not suggest that PMDD and PPD share similar
      pathophysiology beyond being ovarian-steroid-triggered mood disorders. The high
      comorbidity of past MDE could contribute to the increased risk both for future
      MDE and for PPD in some women with PMDD.

PMID- 27035702
TI  - Tenofovir and bone: age-dependent effects in a zebrafish animal model.
AB  - BACKGROUND: New drugs against HIV infection are associated with important side
      effects, including impaired bone health. An important reduction of bone mineral
      density has been repeatedly described in adult but not in young patients
      receiving tenofovir disoproxil fumarate (TDF) as part of their antiretroviral
      regimen. The present study aimed to verify the presence and the characteristics
      of the adverse effects of TDF on skeletal tissue by using the Danio rerio
      (zebrafish) model. METHODS: TDF administration via microinjection in the yolk has
      been used for embryo study. Water treatment with TDF and scale analysis by
      morphological, histological and biochemical experiments have been used for adult
      animals. RESULTS: TDF administration via microinjection in the yolk did not
      induce any significant effect on mineralization rate and did not produce
      deformity of the skeletal structure, or growth or vitality impairment of the
      embryos. TDF exposure in adult zebrafish induced an age-related reduction of the
      osteoblastic activity marker alkaline phosphatase (up to -44%) and an increase of
      the osteoclastic activity marker tartrate-resistant acid phosphatase (up to +57%)
      in the scales. Old fish treated with TDF exhibited an osteoporotic-like phenotype
      with resorption area along the edge of the scale. CONCLUSIONS: This study
      demonstrated that in zebrafish, as in humans, TDF shows a catabolic bone effect
      related to age and underlined the ultimate utility of using teleost fish as a
      model to assess the effects of drugs on bone tissue.

PMID- 27035703
TI  - New Zeno-Like Liquid States.
AB  - A Zeno line is a straight line in a fluid's temperature-density plane where the
      compressibility factor equals unity and stretches from supercritical to
      subcritical regimes. A second unexpected linearity also occurs in liquids in
      their normal liquid range (NLR) where the compressibility factor approaches zero.
      This Zeno-like line includes liquids as diverse as monatomic and diatomic
      elements to hydrogen bonding liquids, with water and helium being the only
      currently known exceptions. Remarkably, this second linearity is also present in
      polymeric liquids, molten metals, and salts, i.e., it is a generic characteristic
      of liquids with negligible or low vapor pressures. This observation yields the
      following new corresponding states principle: Saturated liquid densities are a
      linear function of temperature in the NLR for molecular, polymeric, inorganic,
      ionic, and metallic liquids and superpose to form a single master curve. Another
      Zeno-like linearity in the NLR has also been identified for the configurational
      energy of many liquids. Extension of this line to zero temperature defines the
      ground state configurational energy of the hypothetical disordered liquid
      (glass).

PMID- 27035704
TI  - Copper-catalyzed carboxylation reactions using carbon dioxide.
AB  - Carbon dioxide (CO2), as a waste of manufacture, is a cheap and abundant C1
      source. Utilization of CO2 for synthesis of carboxylic acids has been developed.
      Transition-metal complexes play a key role in catalytic carboxylation reactions
      employing CO2. This review summarizes recent advances in copper-catalyzed
      carboxylation reactions using CO2. The contents are arranged based on various
      substrates: organometallic reagents, aryl iodides, sodium sulfinates, terminal
      alkynes, arenes, heteroarenes, and unsaturated substrates. 

PMID- 27035705
TI  - Microbial diversity arising from thermodynamic constraints.
AB  - The microbial world displays an immense taxonomic diversity. This diversity is
      manifested also in a multitude of metabolic pathways that can utilise different
      substrates and produce different products. Here, we propose that these
      observations directly link to thermodynamic constraints that inherently arise
      from the metabolic basis of microbial growth. We show that thermodynamic
      constraints can enable coexistence of microbes that utilise the same substrate
      but produce different end products. We find that this thermodynamics-driven
      emergence of diversity is most relevant for metabolic conversions with low free
      energy as seen for example under anaerobic conditions, where population dynamics
      is governed by thermodynamic effects rather than kinetic factors such as
      substrate uptake rates. These findings provide a general understanding of the
      microbial diversity based on the first principles of thermodynamics. As such they
      provide a thermodynamics-based framework for explaining the observed microbial
      diversity in different natural and synthetic environments.

PMID- 27035706
TI  - Correction: The Grand Convergence: Closing the Divide between Public Health
      Funding and Global Health Needs.

PMID- 27035707
TI  - Highly efficient photoelectrochemical water splitting by a hybrid tandem
      perovskite solar cell.
AB  - Herein, we show that graphene can be fully utilized to function as an
      electrocatalyst in highly efficient photoelectrochemical water splitting.
      Combining a solution-processed organic photovoltaic and the state-of-the-art
      perovskite solar cell in a tandem architecture yields a stable short-circuit
      water splitting photocurrent of ~7.25 mA cm(-2) under 1 sun illumination. The
      ~7.25 mA cm(-2) photocurrent corresponds to a solar-to-hydrogen efficiency of
      9.02%, which is the highest efficiency yet reported for water splitting based on
      a hybrid tandem perovskite solar cell. 

PMID- 27035708
TI  - Possible association of CCDC62 rs12817488 polymorphism and Parkinson's disease
      risk in Chinese population: a meta-analysis.
AB  - Conflicting results identifying the association between coiled-coil domain
      containing 62 (CCDC62) polymorphism, rs12817488, and Parkinson's disease (PD)
      have been reported. To clarify whether rs12817488 is related to PD risk in
      Chinese population, we carried out this meta-analysis by searching literature
      from PubMed and Embase database regarding this polymorphism. Three eligible
      studies involving 1616 cases and 1649 controls were included in this meta
      analysis. Our results showed statistically significant association between
      rs12817488 and PD risk in all four genetic models. Stratification by gender
      revealed similar results in both subgroup in these genetic models except for
      recessive model, in which rs12817488 was not significantly associated with PD in
      male subgroup. Unstable result was found in recessive model via sensitivity
      analysis, and publication bias was observed in recessive model as well,
      indicating that the pooled result from recessive model should be cautiously
      treated. Our meta-analysis implicates a possible relationship between rs12817488
      and PD risk in Chinese population. Further validation of this association in
      large sample size study with different gender is warranted. 

PMID- 27035709
TI  - A New Model for Size-Dependent Tree Growth in Forests.
AB  - Tree growth, especially diameter growth of tree stems, is an important issue for
      understanding the productivity and dynamics of forest stands. Metabolic scaling
      theory predicted that the 2/3 power of stem diameter at a certain time is a
      linear function of the 2/3 power of the initial diameter and that the diameter
      growth rate scales to the 1/3 power of the initial diameter. We tested these
      predictions of the metabolic scaling theory for 11 Japanese secondary forests at
      various growth stages. The predictions were not supported by the data, especially
      in younger stands. Alternatively, we proposed a new theoretical model for stem
      diameter growth on the basis of six assumptions. All these assumptions were
      supported by the data. The model produced a nearly linear to curvilinear
      relationship between the 2/3 power of stem diameters at two different times. It
      also fitted well to the curvilinear relationship between diameter growth rate and
      the initial diameter. Our model fitted better than the metabolic scaling theory,
      suggesting the importance of asymmetric competition among trees, which has not
      been incorporated in the metabolic scaling theory. 

PMID- 27035710
TI  - Comparative Genomic Analysis Reveals a Possible Novel Non-Tuberculous
      Mycobacterium Species with High Pathogenic Potential.
AB  - Mycobacteria have been reported to cause a wide range of human diseases. We
      present the first whole-genome study of a Non-Tuberculous Mycobacterium,
      Mycobacterium sp. UM_CSW (referred to hereafter as UM_CSW), isolated from a
      patient diagnosed with bronchiectasis. Our data suggest that this clinical
      isolate is likely a novel mycobacterial species, supported by clear evidence from
      molecular phylogenetic, comparative genomic, ANI and AAI analyses. UM_CSW is
      closely related to the Mycobacterium avium complex. While it has characteristic
      features of an environmental bacterium, it also shows a high pathogenic potential
      with the presence of a wide variety of putative genes related to bacterial
      virulence and shares very similar pathogenomic profiles with the known pathogenic
      mycobacterial species. Thus, we conclude that this possible novel Mycobacterium
      species should be tightly monitored for its possible causative role in human
      infections. 

PMID- 27035711
TI  - SAMA: A Method for 3D Morphological Analysis.
AB  - Three-dimensional (3D) culture models are critical tools for understanding tissue
      morphogenesis. A key requirement for their analysis is the ability to reconstruct
      the tissue into computational models that allow quantitative evaluation of the
      formed structures. Here, we present Software for Automated Morphological Analysis
      (SAMA), a method by which epithelial structures grown in 3D cultures can be
      imaged, reconstructed and analyzed with minimum human intervention. SAMA allows
      quantitative analysis of key features of epithelial morphogenesis such as ductal
      elongation, branching and lumen formation that distinguish different hormonal
      treatments. SAMA is a user-friendly set of customized macros operated via FIJI
      (http://fiji.sc/Fiji), an open-source image analysis platform in combination with
      a set of functions in R (http://www.r-project.org/), an open-source program for
      statistical analysis. SAMA enables a rapid, exhaustive and quantitative 3D
      analysis of the shape of a population of structures in a 3D image. SAMA is cross
      platform, licensed under the GPLv3 and available at
      http://montevil.theobio.org/content/sama. 

PMID- 27035712
TI  - Ecology of the Tick-Borne Phlebovirus Causing Severe Fever with Thrombocytopenia
      Syndrome in an Endemic Area of China.
AB  - BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS
      virus (SFTSV), a tick-borne phlebovirus in family Bunyaviridae. Studies have
      found that humans, domestic and wildlife animals can be infected by SFTSV.
      However, the viral ecology, circulation, and transmission remain largely unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: Sixty seven human SFTS cases were reported and
      confirmed by virus isolation or immunofluorescence assay between 2011 and 2014.
      In 2013-2014 we collected 9,984 ticks from either vegetation or small wild
      mammals in the endemic area in Jiangsu, China, and detected SFTSV-RNA by real
      time RT-PCR in both questing and feeding Haemaphysalis longicornis and H. flava.
      Viral RNA was identified in larvae of H. longicornis prior to a first blood meal,
      which has never been confirmed previously in nature. SFTSV-RNA and antibodies
      were also detected by RT-PCR and ELISA, respectively, in wild mammals including
      Erinaceus europaeus and Sorex araneus. A live SFTSV was isolated from Erinaceus
      europaeus captured during the off tick-feeding season and with a high SFTSV
      antibody titer. Furthermore, SFTSV antibodies were detected in the migratory
      birds Anser cygnoides and Streptopelia chinensis using ELISA.
      CONCLUSIONS/SIGNIFICANCE: The detection of SFTSV-RNA in non-engorged larvae
      indicated that vertical transmission of SFTSV in H. longicornis might occur in
      nature, which suggests that H. longicornis is a putative reservoir host of SFTSV.
      Small wild mammals such as Erinaceus europaeus and Sorex araneus could be
      infected by SFTSV and may serve as natural amplifying hosts. Our data unveiled
      that wild birds could be infected with SFTSV or carry SFTSV-infected ticks and
      thus might contribute to the long-distance spread of SFTSV via migratory flyways.
      These findings provide novel insights for understanding SFTSV ecology, reservoir
      hosts, and transmission in nature and will help develop new measures in
      preventing its rapid spread both regionally and globally.

PMID- 27035713
TI  - Development of a Bifunctional Andrographolide-Based Chemical Probe for
      Pharmacological Study.
AB  - Andrographolide (ANDRO) is a lactone diterpenoid compound present in the
      medicinal plant Andrographis paniculata which is clinically applied for multiple
      human diseases in Asia and Europe. The pharmacological activities of
      andrographolide have been widely demonstrated, including anti-inflammation, anti
      cancer and hepatoprotection. However, the pharmacological mechanism of
      andrographolide remains unclear. Therefore, further characterization on the
      kinetics and molecular targets of andrographolide is essential. In this study, we
      described the synthesis and characterization of a novel fluorescent
      andrographolide derivative (ANDRO-NBD). ANDRO-NBD exhibited a comparable anti
      cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of
      cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD
      treatment induced the cleavage of heat shock protein 90 (Hsp90) and the
      downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD
      showed superior inhibitory effects to andrographolide in all anticancer assays we
      have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to
      investigate the uptake kinetics, cellular distribution and molecular targets of
      andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its
      fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and
      lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to
      several putative target proteins of andrographolide, including NF-kappaB and
      hnRNPK. In summary, we developed a fluorescent andrographolide probe with
      comparable bioactivity to andrographolide, which serves as a powerful tool to
      explore the pharmacological mechanism of andrographolide. 

PMID- 27035714
TI  - Neurosurgical Work during the Napoleonic Wars: George James Guthrie's Experience.
AB  - Involved in what is still considered, along with the two world wars of the 20th
      century, as one of the major conflicts in Europe, George James Guthrie (1785
      1856) was the most famous English army surgeon of the Napoleonic wars. After
      treating the injured throughout the Peninsular Campaign (1808-1814), in 1815 and
      then in 1842 he published two major books dealing with cranial and brain
      injuries, among other topics. In these books, we can find, for example, an early
      description of the plantar reflex further described by Joseph Babinsky, accurate
      descriptions of the clinical signs of intracranial hypertension, and details of
      the physiopathology of subdural and epidural haematomas. Skull fractures are also
      discussed intensively, along with the indications for trepanation, a much-debated
      issue at the turn of the 19th century. The dura was often the limit of the
      surgical field for Guthrie. Nevertheless, he tried to rationalize the use of
      trepanation and favoured its use in two main cases: in cases of depressed skull
      bones, jammed bone fragments or debris irritating the dura or the brain and in
      cases of life-threatening cerebral compression caused by supposed blood clots. In
      their works, Guthrie and his contemporaries did not address neurosurgery in the
      modern sense of the word, but rather 'cranial surgery' in most cases. Guthrie,
      who saw so many patients with brain injuries and amputations, failed to
      understand that cerebral functions could be localized to the cortex and neglected
      to describe the phantom limb phenomenon, as did most of his contemporaries. 

PMID- 27035715
TI  - Recombinant Dengue 2 Virus NS3 Helicase Protein Enhances Antibody and T-Cell
      Response of Purified Inactivated Vaccine.
AB  - Dengue virus purified inactivated vaccines (PIV) are highly immunogenic and
      protective over the short term, but may be poor at inducing cell-mediated immune
      responses and long-term protection. The dengue nonstructural protein 3 (NS3) is
      considered the main target for T-cell responses during viral infection. The amino
      (N)-terminal protease and the carboxy (C)-terminal helicase domains of DENV-2 NS3
      were expressed in E. coli and analyzed for their immune-potentiating capacity.
      Mice were immunized with DENV-2 PIV with and without recombinant NS3 protease or
      NS3 helicase proteins, and NS3 proteins alone on days 0, 14 and 28. The NS3
      helicase but not the NS3 protease was effective in inducing T-cell responses
      quantified by IFN-gamma ELISPOT. In addition, markedly increased total IgG
      antibody titer against virus antigen was seen in mice immunized with the PIV/NS3
      helicase combination in the ELISA, as well as increased neutralizing antibody
      titer measured by the plaque reduction neutralization test. These results
      indicate the potential immunogenic properties of the NS3 helicase protein and its
      use in a dengue vaccine formulation. 

PMID- 27035717
TI  - What's in a Name? Neurological Eponyms of the Nazi Era.
AB  - The 1920s were a booming decade for neuroscience, and perhaps nowhere was this
      truer than in Germany. Following the rise of Hitler's regime and the persecution
      of Jews and others, however, Germany and Austria lost numerous world-class
      neuroscientists. Vacant posts were quickly filled with 'Aryan' and academic staff
      loyal to the Nazis. Indeed, many physicians and scientists went even further and
      became engaged in National Socialist (NS)-euthanasia programs. In recent years,
      the medical community has become more aware of the ethical burden associated with
      eponyms derived from scientists of the Third Reich. This book chapter reviews 53
      neurological eponyms derived from physicians who worked in the Nazi era. Among
      them are victims who were forced out of the country or murdered in concentration
      camps, protestors who risked their academic careers and often their lives,
      beneficiaries who published on brains from 'euthanized' children, and
      collaborators who were directly involved in the planning and execution of NS
      euthanasia programs. 

PMID- 27035716
TI  - Bleeding Efficiency, Microbiological Quality and Oxidative Stability of Meat from
      Goats Subjected to Slaughter without Stunning in Comparison with Different
      Methods of Pre-Slaughter Electrical Stunning.
AB  - The influence of pre-slaughter electrical stunning techniques and slaughter
      without stunning on bleeding efficiency and shelf life of chevon during a 14 d
      postmortem aging were assessed. Thirty two Boer crossbred bucks were randomly
      assigned to four slaughtering techniques viz slaughter without stunning (SWS),
      low frequency head-only electrical stunning (LFHO; 1 A for 3 s at a frequency of
      50 Hz), low frequency head-to-back electrical stunning (LFHB; 1 A for 3 s at a
      frequency of 50 Hz) and high frequency head-to-back electrical stunning (HFHB; 1
      A for 3 s at a frequency of 850 Hz). The SWS, LFHO and HFHB goats had higher
      (p<0.05) blood loss and lower residual hemoglobin in muscle compared to LFHB. The
      LFHB meat had higher (p<0.05) TBARS value than other treatments on d 7 and 14 d
      postmortem. Slaughtering methods had no effect on protein oxidation. Higher
      bacterial counts were observed in LFHB meat compared to those from SWS, LFHO and
      HFHB after 3 d postmortem. Results indicate that the low bleed-out in LFHB
      lowered the lipid oxidative stability and microbiological quality of chevon
      during aging. 

PMID- 27035718
TI  - The antihistamine olopatadine regulates T cell activation in palladium allergy.
AB  - Because of its corrosion resistance palladium (Pd) has been widely used in many
      consumer products ranging from fashion accessories to dental materials. Recently,
      however, an increase in Pd allergy cases has been reported. Metal allergy is
      categorized as a Type IV allergy, which is characterized as a delayed-type
      hypersensitivity reaction in which T cells are known to play an important role;
      however, the precise mechanism of their action remains unclear. Here we defined
      the relationship between histamine and the Pd allergic reaction specifically with
      respect to T cell responses. To verify the effects of histamine on T cells, we
      examined whether there is a change in IFN-gamma production following stimulation
      of histamine or the antihistamine, olopatadine hydrochloride (OLP), in vitro. In
      addition, we assessed whether OLP administration affected the degree of footpad
      swelling or IFN-gamma production during the Pd allergy response in mice. We found
      that histamine stimulation increased IFN-gamma production in T cells,
      specifically enhancing IFN-gamma production in CD8(+) T cells compared with
      CD4(+) T cells. Interestingly, OLP suppressed the production of IFN-gamma in
      CD8(+) T cells, and this compound inhibited footpad swelling and IFN-gamma
      production in mice with Pd allergy. These results suggest that histamine promotes
      the Type IV allergic reaction and thus, the histamine 1 receptor (H1R) might be
      useful therapeutic target for treatment of metal allergy. 

PMID- 27035719
TI  - Rutin ameliorates kidney interstitial fibrosis in rats with obstructive
      nephropathy.
AB  - Rutin reportedly conveys many beneficial effects, including renoprotection;
      however, it has not yet been demonstrated to have a renoprotective effect against
      obstructive nephropathy. The present study is the first to show a protective
      effect of rutin against obstructive renal injury induced by unilateral ureteral
      obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four
      groups of six rats each, including vehicle- or rutin-treated sham operated
      groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage
      of rutin (100mg/kg) for 2weeks. All rats were euthanized on postoperative day 14.
      Histological findings showed that rutin administration significantly reduced
      renal interstitial injury and suppressed interstitial collagen deposits in UUO
      rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine
      expression and phosphorylation of nuclear factor-kappaB p65. Furthermore, rutin
      inhibited extracellular matrix accumulation by reducing expression of type I/III
      collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal
      transition processes of renal tubular cells by decreasing alpha-smooth muscle
      actin expression and retaining E-cadherin expression. These effects of rutin were
      in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic
      potential of TGF-beta1. Taken together, the renoprotective effects of rutin in
      obstructive nephropathy were likely due to anti-inflammatory effects and
      inhibition of TGF-beta1/Smad3 signaling. 

PMID- 27035720
TI  - Serum Vitamin D and Facial Aging: Is There a Link?
AB  - BACKGROUND: The vitamin D endocrine system, besides multiple other functions,
      regulates aging in many tissues, including the skin. It protects the skin against
      the hazardous effects of many skin age-inducing agents, including ultraviolet
      radiation. Thus, in the present study we aimed to investigate the relationship
      between facial skin aging and 25-hydroxyvitamin D [25(OH)D] serum levels in
      healthy Egyptian adults. METHODS: Sixty-one healthy adult subjects were included.
      Photodamage scores (erythema/telangiectasias, lentigines, hyperpigmentation and
      coarse wrinkling) were assessed and graded. Serum vitamin D was measured using
      enzyme immunoassay and subjects were classified as sufficient, insufficient or
      deficient according to the vitamin level. RESULTS: The mean 25(OH)D serum level
      was 43.90 nmol/l. A high prevalence of vitamin D deficiency was detected in the
      studied subjects regardless of their age or gender. Also, vitamin D levels were
      not correlated with photodamage scores and were not affected by the Fitzpatrick
      skin phototype, duration of sun exposure per day or the use of sunscreens (p >
      0.05 for all). CONCLUSIONS: Aging is a complex process that is influenced by many
      genetic and environmental factors. Facial aging is not correlated with serum
      vitamin D level, and clinical trials using oral or topical vitamin D to combat
      aging are better predictors of its effects rather than in vivo studies.

PMID- 27035721
TI  - Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes.
AB  - Genetic and molecular studies have provided considerable insight into how various
      tissue progenitors are specified in early embryogenesis, but much less is known
      about how those progenitors create three-dimensional tissues and organs. The C.
      elegans intestine provides a simple system for studying how a single progenitor,
      the E blastomere, builds an epithelial tube of 20 cells. As the E descendants
      divide, they form a primordium that transitions between different shapes over
      time. We used cell contours, traced from confocal optical z-stacks, to build a 3D
      graphic reconstruction of intestine development. The reconstruction revealed
      several new aspects of morphogenesis that extend and clarify previous
      observations. The first 8 E descendants form a plane of four right cells and four
      left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh
      dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects
      the left cells in the E8 primordium, and initiates later asymmetry in cell
      packing. The next few stages involve cell repositioning and intercalation events
      that shuttle cells to their final positions, like shifting blocks in a Rubik's
      cube. Repositioning involves breaking and replacing specific adhesive contacts,
      and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX
      3/Robo. Once cells in the primordium align along a common axis and in the correct
      order, cells at the anterior end rotate clockwise around the axis of the
      intestine. The anterior rotation appears to align segments of the developing
      lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin,
      the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous
      studies showed that rotation requires a second round of LIN-12/Notch signaling in
      cells on the right side of the primordium, and we show that MADD-2-GFP appears to
      be downregulated in those cells. 

PMID- 27035722
TI  - Alcohol Consumption Practices among Married Women of Reproductive Age in Nepal: A
      Population Based Household Survey.
AB  - BACKGROUND: Alcohol chemically known as ethanol, causes several health, economic
      and social consequences across the world. Literatures suggest potential harm of
      alcohol drinking by pregnant women especially to the fetus and the mother.
      Despite a number of significant public health problems related to alcohol
      consumption, this area has been ignored in Nepal and information at the national
      level is limited. Thus this study aimed at finding the prevalence of alcohol
      consumption among married women of reproductive age. METHODS: A nationally
      representative household survey was carried out from April to August 2013 by
      taking 16 districts across all 15 eco administrative regions. From the selected
      districts, 86 village development committees and 14 municipalities were selected
      as primary sampling units using probability proportionate to size, followed by
      random selection of 3 wards from each primary sampling unit. Finally, 30
      households within each ward were selected using systematic random sampling, and
      one married women of reproductive age from each household. A total of 9000
      married women of reproductive age were interviewed using a semi-structured
      questionnaire, on alcohol consumption practices including environmental factors
      and socio demographic characteristics and were included in the analysis. RESULTS:
      National prevalence of alcohol consumption ever among married women of
      reproductive age was 24.7% (95% CI:21.7-28.0), last 12 months 17.9% (95% CI:15.3
      20.7) and last 30 days (current drinking) 11.8% (95% CI:9.8-14.1). There was
      substantial variation among the districts ranging from 2% to 60%. Multivariable
      analysis suggests women with no education or within formal education, dalit and
      janajatis ethnicity, whose husbands drink alcohol, who brew alcohol at home and
      women from mountains were significantly at higher risk of consuming alcohol.
      Among the women who drank alcohol in last 12 months, a substantial proportion of
      them drank home brewed alcoholic beverages (95.9%, 95% CI:94.3-97.4). CONCLUSION:
      Alcohol consumption was common practice among married women of reproductive age
      in Nepal with variation among the subgroups of population. Thus, further
      investigation and behavior change communication interventions to reduce alcohol
      consumption especially among the women with higher risk of drinking is essential.

PMID- 27035724
TI  - Programme for invited speakers and abstracts selected for oral presentation.

PMID- 27035723
TI  - Circulating LncRNAs as Novel, Non-Invasive Biomarkers for Prenatal Detection of
      Fetal Congenital Heart Defects.
AB  - OBJECTIVES: To explore the clinical value of circulating long non-coding RNAs
      (lncRNAs) as biomarkers to predict fetal congenital heart defects (CHD) in
      pregnant women. METHODS: Differential expression of lncRNAs isolated from the
      plasma of pregnant women with typical fetal CHD or healthy controls was analyzed
      by microarray. Gene ontology (GO), pathway and network analysis were performed to
      study the function of the lncRNAs. Differentially expressed lncRNAs were
      validated in plasma samples from 62 pregnant women with typical CHD and 62
      matched controls by RT-PCR. The sensitivity and specificity of each lncRNA in the
      diagnosis of fetal CHD was determined by ROC curve analysis. RESULTS: Microarray
      analysis identified 3694 up-regulated and 3919 down-regulated (fold change >=2.0)
      lncRNAs. The top ten significantly differentially expressed, CHD-associated
      lncRNAs were validated by RT-PCR. Five significantly up-regulated or down
      regulated lncRNAs were identified: ENST00000436681, ENST00000422826, AA584040,
      AA709223 and BX478947 with the AUC of ROC curves calculated as 0.892, 0.817,
      0.755, 0.882 and 0.886, respectively. CONCLUSIONS: Specific lncRNAs aberrantly
      expressed in the plasma of pregnant women with typical fetal CHD may play a key
      role in the development of CHD and may be used as novel biomarkers for prenatal
      diagnosis of fetal CHD.

PMID- 27035726
TI  - French Neurologists during World War I.
AB  - The Great War accelerated the development of neurological knowledge. Many
      neurological signs and syndromes, as well as new nosological entities such as war
      psychoneuroses, were described during the conflict. The period between 1914 and
      1918 was the first time in which many neurologists were concentrated in wartime
      neurology centres and confronted with a number of neurological patients never
      seen before. This concentration led to the publication of papers concerning all
      fields of neurological sciences, and these reports pervaded scientific journals
      during the conflict and the post-war years. The careers of French neurologists
      during the war were highly varied. Some were mobilised, whilst others enlisted
      voluntarily. They worked as regiment physicians at the front or in wartime
      neurology centres at the front or at the rear. Others were academics who were
      already authoritative names in the field of neurology. Whilst they were too old
      to be officially mobilised, they nevertheless worked in their militarised
      neurology departments of civil hospitals. We present here the careers of a few
      French neurologists during the Great War, including Charles Foix (1882-1927),
      Rene Cruchet (1875-1959), Georges Guillain (1876-1961), Jean Lhermitte (1877
      1959), Clovis Vincent (1879-1947), Gustave Roussy (1874-1948), and Paul Sollier
      (1861-1933). 

PMID- 27035727
TI  - Tracing Single Electrons in a Disordered Polymer Film at Room Temperature.
AB  - The transport of charges lies at the heart of essentially all modern (opto-)
      electronic devices. Although inorganic semiconductors built the basis for current
      technologies, organic materials have become increasingly important in recent
      years. However, organic matter is often highly disordered, which directly impacts
      the charge carrier dynamics. To understand and optimize device performance,
      detailed knowledge of the transport mechanisms of charge carriers in disordered
      matter is therefore of crucial importance. Here we report on the observation of
      the motion of single electrons within a disordered polymer film at room
      temperature, using single organic chromophores as probe molecules. The migration
      of a single electron gives rise to a varying electric field in its vicinity,
      which is registered via a shift of the emission spectra (Stark shift) of a
      chromophore. The spectral shifts allow us to determine the electron mobility and
      reveal for each nanoenvironment a distinct number of different possible electron
      transfer pathways within the rugged energy landscape of the disordered polymer
      matrix. 

PMID- 27035728
TI  - Improving Medication Adherence and Health Care Outcomes in a Commercial
      Population through a Community Pharmacy.
AB  - The aim was to evaluate the impact of a multifaceted set of medication management
      interventions offered by a community pharmacy on adherence, health care
      utilization, and costs within a commercial population. Patients initiating
      therapy within 16 drug classes from February 7, 2013, to October 6, 2013, were
      offered various adherence interventions by Walgreens pharmacy. Patients were
      linked deterministically to IMS medical and prescription databases for 6-month
      pre- and post-index data analysis. Walgreens patients (intervention) were matched
      to patients using other pharmacies (control) on drug class, index date, baseline
      demographics, clinical factors, utilization, and costs. Outcomes were evaluated
      at the intent-to-treat level using post-index differences and generalized
      estimating equations (GEE) regression model. Paired t tests (continuous
      variables) and McNemar's test (dichotomous variables) were used to determine the
      significance of estimated model coefficients at alpha = 0.05. The groups (n =
      72,410 each) had similar age (47.1 vs. 45.7 years), sex (41.2% vs. 40.2% male),
      and disease burden (0.52 vs. 0.40 mean Charlson comorbidity index). In the 6
      month post-index period, the intervention group had 3.0% greater medication
      adherence, 1.8% fewer hospital admissions, 2.7% fewer emergency room (ER) visits,
      and 0.53 fewer mean outpatient visits compared to the control group (all P <
      0.0001). The intervention group incurred significantly lower GEE-adjusted
      pharmacy costs (-$92), outpatient costs (-$120), ER costs (-$38), and total
      health care costs (-$226.07) (all P < 0.0001), and higher inpatient costs ($86, P
      < 0.004) per patient. A multifaceted set of medication management interventions
      offered by a community pharmacy were associated with patients in a commercial
      population having significantly higher medication adherence and lower health care
      utilization and costs.

PMID- 27035729
TI  - Family environment as a moderator of the association between anxiety and suicidal
      ideation.
AB  - The present study examined associations among anxiety symptoms, anxiety disorder
      diagnoses, perceptions of family support and conflict, and suicidal ideation (SI)
      in a clinical sample of psychiatrically hospitalized adolescents. Participants
      were 185 adolescents (72% female; 84% white, mean age=15.02years, SD=1.33)
      hospitalized on an acute psychiatric inpatient unit. Results indicated that
      anxiety disorders and symptoms were positively associated with SI, even after
      controlling for mood disorder diagnoses and sex. Moreover, this relationship was
      stronger among youth who reported lower (versus higher) levels of family support.
      Family conflict was positively associated with SI but did not moderate the
      relationship between anxiety and SI. Results suggest that family support may
      represent an important intervention target to decrease suicide risk among anxious
      youth. Integrating positive parenting techniques (e.g., attending to positive
      behaviors, providing praise, emotion coaching) and effective parent-child
      communication into treatment with anxious youth may help achieve this aim.

PMID- 27035730
TI  - Valence processing of first impressions in the dorsomedial prefrontal cortex: a
      near-infrared spectroscopy study.
AB  - Previous studies have suggested that the dorsomedial prefrontal cortex (dmPFC)
      plays a central role in processing first impressions; however, little is known
      about how dmPFC processes different valences of first impressions. Moreover, it
      is still unclear as to whether the dmPFC shows lateralization or only induces
      different levels of activation when processing positive and negative impressions.
      To address these questions in the present study, the brain activities for the
      impression judgments expressed by participants were measured with near-infrared
      spectroscopy. For each real facial picture, participants were asked to evaluate
      their first impressions on a scale from 'bad' to 'good' using a keyboard. The
      results showed that although the right dmPFC has a higher sensitivity in
      processing impressions, both the hemispheres of dmPFC showed a significant trend
      where the activation of positive impressions was higher than the negative ones.
      Accordingly, it is proposed that the dmPFC acts as a single mechanism responsible
      for delineating the processing of first impressions rather than two lateralized
      systems. Therefore, a 'positivity dominance hypothesis' is also proposed, which
      states that dmPFC in both hemispheres have a higher sensitivity and priority for
      positive impressions than negative ones. The present study provides valuable
      findings with respect to the role of the dmPFC in the processes of first
      impression formation.

PMID- 27035731
TI  - Functional significance of the semantic P600: evidence from the event-related
      brain potential source localization.
AB  - Previous event-related potentials studies of sentence comprehension have usually
      associated syntactic repair/reanalysis processes with the P600 component.
      However, the functional significance of the P600 was recently questioned on the
      basis of the observation of P600 effects in response to the processing of
      semantically anomalous sentences. In the present study, we investigated the
      functional significance of the 'semantic P600' using a semantic violation
      paradigm with a focus-on-syntax instruction. Using a source localization
      analysis, we tested three alternative hypotheses on the function of the P600: (i)
      a syntactic function, (ii) an executive function, and (iii) a
      semantic/integrational function. We assumed that distinct neuronal generators
      should reflect each of these functions. Although the syntactic generators are
      expected to be mainly located in the left inferior frontal gyrus, the semantic
      generators should be observed in the left superior temporal gyrus as well as in
      the right anterior prefrontal cortex (semantic retrieval); moreover, the
      generator of executive function (conflict monitoring) should be found in the
      anterior cingulate cortex. Critically, we defined a dipole model using 17
      dipoles, 14 of which were placed in the three regions of interest corresponding
      to our hypotheses, namely, syntactic, executive, and semantic regions. Our data
      showed that the P600 effect was significant in the anterior cingulate cortex and
      marginally significant in the right anterior prefrontal cortex. This finding
      suggests that the P600 might reflect more general mechanisms of conflict
      monitoring and semantic reinterpretation leading to a retrieval of world
      knowledge from long-term memory rather purely syntactic processes. 

PMID- 27035732
TI  - In vitro chondrogenic commitment of human Wharton's jelly stem cells by co
      culture with human articular chondrocytes.
AB  - Wharton's jelly stem cells (WJSCs) are a potential source of transplantable stem
      cells in cartilage-regenerative strategies, due to their highly proliferative and
      multilineage differentiation capacity. We hypothesized that a non-direct co
      culture system with human articular chondrocytes (hACs) could enhance the
      potential chondrogenic phenotype of hWJSCs during the expansion phase compared to
      those expanded in monoculture conditions. Primary hWJSCs were cultured in the
      bottom of a multiwell plate separated by a porous transwell membrane insert
      seeded with hACs. No statistically significant differences in hWJSCs duplication
      number were observed under either of the culture conditions during the expansion
      phase. hWJSCs under co-culture conditions show upregulations of collagen type I
      and II, COMP, TGFbeta1 and aggrecan, as well as of the main cartilage
      transcription factor, SOX9, when compared to those cultured in the absence of
      chondrocytes. Chondrogenic differentiation of hWJSCs, previously expanded in co
      culture and monoculture conditions, was evaluated for each cellular passage using
      the micromass culture model. Cells expanded in co-culture showed higher
      accumulation of glycosaminoglycans (GAGs) compared to cells in monoculture, and
      immunohistochemistry for localization of collagen type I revealed a strong
      detection signal when hWJSCs were expanded under monoculture conditions. In
      contrast, type II collagen was detected when cells were expanded under co-culture
      conditions, where numerous round-shaped cell clusters were observed. Using a
      micromass differentiation model, hWJSCs, previously exposed to soluble factors
      secreted by hACs, were able to express higher levels of chondrogenic genes with
      deposition of cartilage extracellular matrix components, suggesting their use as
      an alternative cell source for treating degenerated cartilage. Copyright (c) 2015
      John Wiley & Sons, Ltd.

PMID- 27035733
TI  - Effect of growth differentiation factor-9 C447T and G546A polymorphisms on the
      outcomes of in vitro fertilization.
AB  - Single nucleotide polymorphisms (SNPs) in the growth differentiation factor (GDF)
      9 gene are associated with premature ovarian failure, insufficient ovarian
      stimulation and a poor in vitro fertilization (IVF) score in women with
      diminished ovarian reserve. The aim of the present study was to assess the effect
      of C447T (rs254286) and G546A (rs10491279) SNPs on ovary stimulation response,
      oocyte quality, fertilization rate and outcome of clinical pregnancy in an
      infertile population of Polish females (n=86) treated with IVF. The present study
      also included a group of fertile women (n=202). The P-trend value, calculated for
      the GDF-9 C447T transition in infertile women, was statistically significant and
      were equal to 0.0195. A significant association of the GDF-9 C447T SNP was
      observed with infertility for the C/C vs. T/T + C/T model (OR= 2.140; 95%
      CI=1.043-4.393; P=0.0349). The GDF-9 G546A SNP was significantly associated with
      the G/A vs. G/G model with poor ovarian stimulation (OR=9.303; 95% CI=2.568
      33.745; P=0.0008) and poor fertilization rate (OR=2.981; 95% CI=1.033-8.607;
      P=0.0385). For the GDF-9 C447T SNP, a significant association was observed
      between the C/C + C/T vs. T/T model and a poor ovarian stimulation response
      (OR=15.309; 95% CI=0.875-267.83; P=0.0078), and a poor fertilization rate
      (OR=4.842; 95% CI=1.310-17.901; P=0.0121). The present genetic evaluation
      revealed associations between IVF outcomes and the GDF-9 A546G and C447T SNPs.
      Additionally, these results indicated that the GDF-9 C447T SNP is a possible
      candidate genetic risk factor for female infertility in the Polish population. 

PMID- 27035734
TI  - Aortic-to-brachial stiffness gradient and kidney function in type 2 diabetes.
AB  - OBJECTIVES: A reversed aortic-to-brachial stiffness gradient (ab-SG), defined as
      aortic pulse wave velocity (aPWV) greater than brachial PWV (bPWV), was recently
      shown to predict mortality independent of aPWV in dialysis patients. Patients
      with type 2 diabetes mellitus (T2DM) have increased risk of renal damage and
      exhibit haemodynamic abnormalities at rest and during exercise that may alter the
      ab-SG. This study aimed to examine ab-SG in patients with T2DM by comparison with
      nondiabetic controls during rest and exercise, and to determine associations
      between ab-SG, aPWV, and kidney function. METHODS: Study participants were 60
      patients with T2DM and 60 age and sex-matched nondiabetic controls (58 +/- 8
      years, 55% male both). ab-SG was defined as the quotient of bPWV (carotid-to
      radial) and aPWV (carotid-to-femoral) recorded via applanation tonometry. Kidney
      function was assessed using estimated glomerular filtration rate (eGFR). The
      exercise substudy was undertaken in 21 patients with T2DM and 21 matched
      nondiabetic controls during semirecumbent exercise. RESULTS: ab-SG was
      significantly lower in patients with T2DM (0.99 +/- 0.2 vs. 1.2 +/- 0.3, P <
      0.001) and aPWV, but not bPWV, was significantly higher (P < 0.001 and P = 0.25).
      A total of 58% of patients with T2DM vs. 27% of nondiabetic controls (chi = 11.0,
      P < 0.001) had a reversed ab-SG (aPWV >= bPWV). ab-SG predicted eGFR independent
      of age, sex, T2DM status, and cardiovascular risk factors (beta = 13.2, P =
      0.024), whereas aPWV did not (beta = -0.88, P = 0.30). Exercise ab-SG was
      significantly lower in patients with T2DM (0.97 +/- 0.2 vs. 1.2 +/- 0.2, P <
      0.001), but did not predict eGFR. CONCLUSIONS: Patients with T2DM have a reversed
      ab-SG during rest and exercise. Resting ab-SG predicts kidney function
      independent of aPWV, implying a reversed ab-SG may have a pathophysiological
      function.

PMID- 27035735
TI  - Impact and pitfalls of scaling of left ventricular and atrial structure in
      population-based studies.
AB  - BACKGROUND: Several allometric methods for indexing cardiac structures to body
      size have been proposed but the optimal way for normalization of cardiac
      structures is still controversial. We aimed to estimate the allometric exponents
      that best describe the relationships between cardiac dimensions and body size,
      propose normative values, and analyze how the different scaling metrics influence
      the prevalence of left ventricular hypertrophy (LVH) and chambers enlargement as
      well as predictive models for cardiovascular outcome in the community. METHODS:
      We measured left ventricular end-diastolic dimension, end-diastolic volume, left
      ventricular mass, and left atrial volume in randomly recruited population cohorts
      (n = 1509; 52.8% women; mean age, 47.8 years). RESULTS: In a healthy subgroup (n
      = 656), the allometric exponents that described the relationships between left
      ventricular end-diastolic dimension and body size were 1, 0.5, and 0.33 for body
      height, body surface area (BSA), and estimated lean body mass, respectively. With
      regard to left ventricular end-diastolic volume, left ventricular mass, and left
      atrial volume the allometric exponents for body height were 2.9, 2.7, and 2.0,
      respectively; for BSA, they ranged from 1.7 to 1.8; for estimated lean body mass
      all exponents were around 1. These exponents were used to appropriately scale the
      cardiac dimensions to body size and derived sex-specific cut-off limits for
      different indexed cardiac dimensions. The hazard ratios of cardiovascular outcome
      were highest for LVH defined by left ventricular mass/height. CONCLUSION: Our
      study resulted in a proposal for thresholds for various indexed cardiac
      dimensions. Left ventricular mass indexed to height was sensitive in detection of
      LVH associated with obesity and slightly better predicted outcome.

PMID- 27035736
TI  - Chronic kidney disease epidemiology collaboration-derived glomerular filtration
      rate performs better at detecting preclinical end-organ changes than alternative
      equations in black Africans.
AB  - AIM: To identify whether the more recently developed equation for estimated
      glomerular filtration rate (eGFR) [Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI)] is more closely associated with end-organ changes than
      previous equations in a group of black African descent. METHODS: In 1221 randomly
      recruited participants of black African ancestry in South Africa, we evaluated
      serum creatinine concentrations, echocardiographic left ventricular mass index (n
      = 833), carotid-femoral (aortic) pulse wave velocity (PWV) (n = 1053) and carotid
      intima-media thickness (n = 633). We calculated eGFR from the Jelliffe, five
      Cockcroft-Gault, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD)
      and CKD-EPI equations. RESULTS: After multivariate adjustments, eGFR calculated
      from all formulae was inversely associated with left ventricular mass index (P <
      0.0001) and PWV (P < 0.05 to <0.001), but not with carotid intima-media thickness
      (P > 0.08). However, although eGFR determined from all equations except Cockcroft
      Gault lean body weight or adjusted body weight was independently associated with
      left ventricular hypertrophy (n = 390 of 833), CKD-EPI-derived eGFR, but not eGFR
      determined from alternative equations, was independently associated with an
      increased PWV (n = 88 of 1053). eGFR derived from the CKD-EPI and MDRD equations
      showed a better performance (area under the receiver operator characteristic
      curve) for the detection of left ventricular hypertrophy (P < 0.0005) than eGFR
      determined from alternative equations. CONCLUSIONS: In black Africans, eGFR
      derived from the CKD-EPI equation is better at detecting end-organ measures than
      eGFR derived from either the MDRD or alternative equations. To enhance risk
      prediction in black African communities, eGFR calculated from the CKD-EPI
      equation may be preferred to other equations.

PMID- 27035737
TI  - Prognostic value of longitudinal strain of subepicardial myocardium in patients
      with hypertension.
AB  - OBJECTIVE: Global longitudinal strain is not well illustrated for the prognostic
      value in hypertension. This observational study investigated the prognostic value
      of global longitudinal strain, subendocardial longitudinal strain, and
      subepicardial (EpiLS) longitudinal strain in regularly treated hypertensive
      patients. METHODS: Ninety-five hypertensive study participants (60.0% men, age
      65.5 +/- 12.0 years) were regularly treated for more than 1 year. We performed a
      two-dimensional echocardiographic study and obtained global peak systolic left
      ventricular longitudinal strain of subendocardial myocardium and the
      subepicardium (defined as subendocardial longitudinal strain and EpiLS,
      respectively). Cardiovascular events included cardiovascular death and any
      admission for stroke, acute coronary syndrome, or heart failure. RESULTS: After a
      follow-up period of 7.3 +/- 2.0 years, 20 (21%) study participants had
      cardiovascular events. Significant differences between study participants with
      and without cardiovascular events were noted in diuretic administration (75.0 vs.
      93.3%, P = 0.018), age (71.0 +/- 11.6 vs. 64.0 +/- 11.8 years, P = 0.02) and
      EpiLS (-16.0 +/- 2.0 vs. -17.7 +/- 3.0%, P = 0.04). Using multivariate Cox
      regression analysis, EpiLS was the only independent prognostic factor (hazard
      ratio 1.449, 95% confidence interval 1.027-2.045, P = 0.035). Using the cut off
      value of -17.57% for EpiLS (median value of EpiLS), the Kaplan-Meier survival
      curve revealed a significant difference (P = 0.016) associated with
      cardiovascular outcome. CONCLUSION: EpiLS was the only independent prognostic
      factor in regularly-treated hypertensive patients. Our results indicated that
      involvement of subepicardial myocardium may infer worse prognosis of hypertensive
      heart disease.

PMID- 27035738
TI  - The Chemical Ecology of Predatory Soil Bacteria.
AB  - The study of natural products is entering a renaissance, driven by the discovery
      that the majority of bacterial secondary metabolites are not produced under
      standard laboratory conditions. Understanding the ecological role of natural
      products is key to efficiently directing our screening efforts, and to ensuring
      that each screen efficiently captures the full biosynthetic repertoire of the
      producing organisms. Myxobacteria represent one of the most common and diverse
      groups of bacteria, with roughly 2500 strains publically available. Fed largely
      through predation, the myxobacteria have developed a large repertoire of natural
      products that target other microorganisms, including bacteria and fungi. Many of
      these interactions can be observed in predation assays, providing direct evidence
      for environmental interactions. With a focus on Myxococcus xanthus, this review
      will highlight how recent advances in myxobacteria are revealing the chemical
      ecology of bacterial natural products.

PMID- 27035739
TI  - Robotic-Assisted Paraesophageal Hernia Repair: Initial Experience at a Single
      Institution.
AB  - BACKGROUND: Laparoscopic surgery is considered the standard approach for the
      treatment of paraesophageal hernias (PEHs). Despite its advantages, this approach
      is technically demanding with a significant learning curve. Data about the safety
      and utility of the robotically assisted paraesophageal hernia repair (RA-PEHR)
      are scarce. The aim of this study is to assess the feasibility and safety of
      robotic assistance for the treatment of PEH. MATERIALS AND METHODS: Between June
      2010 and December 2015, patients who underwent elective RA-PEHR were included in
      a prospectively collected database. Demographic data, American Society of
      Anesthesiologists (ASA) classification, preoperative testing, operative time
      (OT), length of hospital stay (LOS), conversion rate, morbidity, and mortality
      were recorded and reviewed retrospectively. RESULTS: Sixty-one patients underwent
      RA-PEHR with mesh, 72% were female (mean age of 63 and mean body mass index [BMI]
      of 30). ASA classification was 2.6 (57% of patients had an ASA III). With respect
      to the type of the hernia, the preoperative diagnosis was: Type II 26%, III 64%,
      and IV 13%. OT averaged 186 minutes (88-360), including robot setup time. After
      the 16th case, OT significantly decreased by 4.09 minutes (P = .01). There were
      no conversions. The average blood loss was 51 mL. Perioperative complications,
      including intraoperative and 30-day complications, were 6% and 23%, respectively.
      The mean length of hospitalization was 2.6 (1-18) days. There were no deaths.
      Forty patients (66%) were available for follow-up, and length of follow-up was 17
      +/- 15 months. Anatomic recurrence was observed in 42% of patients and only 23%
      of patients were symptomatic. CONCLUSIONS: This report represents the largest
      series to date of RA-PEHR. RA-PEHR has proved to be feasible and safe with a
      learning curve comparable to the standard laparoscopic approach.

PMID- 27035740
TI  - Enhanced thermoelectric properties of graphene oxide patterned by nanoroads.
AB  - The thermoelectric properties of two-dimensional (2D) materials are of great
      interest for both fundamental science and device applications. Graphene oxide
      (GO), whose physical properties are highly tailorable by chemical and structural
      modifications, is a potential 2D thermoelectric material. In this report, we
      pattern nanoroads on GO sheets with epoxide functionalization, and investigate
      their ballistic thermoelectric transport properties based on density functional
      theory and the nonequilibrium Green's function method. These graphene oxide
      nanoroads (GONRDs) are all semiconductors with their band gaps tunable by the
      road width, edge orientation, and the structure of the GO matrix. These
      nanostructures show appreciable electrical conductance at certain doping levels
      and enhanced thermopower of 127-287 MUV K(-1), yielding a power factor 4-22 times
      of the graphene value; meanwhile, the lattice thermal conductance is remarkably
      reduced to 15-22% of the graphene value; consequently, attaining the figure of
      merit of 0.05-0.75. Our theoretical results are not only helpful for
      understanding the thermoelectric properties of graphene and its derivatives, but
      also would guide the theoretical design and experimental fabrication of graphene
      based thermoelectric devices of high performance.

PMID- 27035741
TI  - Erythronium japonicum attenuates histopathological lung abnormalities in a mouse
      model of ovalbumin-induced asthma.
AB  - Asthma is a chronic lung condition that can induce mucus hypersecretion and
      pulmonary obstruction and may even cause death, particularly in children and
      older individuals. Erythronium japonicum (E. japonicum) is a traditional herb
      used in Korea and East Asian countries that has been found to exert free radical
      scavenging activity and anti-proliferative effects in human colorectal carcinoma
      cells. In the present study, we evaluated the anti-asthmatic effects of an
      extract of E. japonicum in a mouse model of ovalbumin (OVA)-induced asthma.
      Female BALB/c mice were sensitized with an intraperitoneal injection of OVA and
      aluminum hydroxide hydrate on days 1 and 8 and then received the following
      treatments on days 21 to 25: i) control (no treatment), ii) sterilized tap water
      (given orally), iii) 1 mg/kg/day dexamethasone (administered orally), iv) 60
      mg/kg/day E. japonicum extract, and v) 600 mg/kg/day E. japonicum extract. On the
      same days, all the mice except those in the control group were challenged 1 h
      later with nebulized 5% OVA for 30 min. We found that treatment with E. japonicum
      extract suppressed the OVA-induced increase in the number of white blood cells
      and decreased the IgE level in the bronchoalveolar lavage fluid samples obtained
      from the mice. Histopathological analysis of the lung tissues revealed that E.
      japonicum attenuated the asthma-related morphological changes in the mouse lung
      tissue, including the increased secretion of mucus in the bronchioles, eosinophil
      infiltration around the bronchioles and vessels, and goblet cell and epithelial
      cell hyperplasia. Immunohistochemical analysis revealed that treatment with E.
      japonicum extract suppressed the OVA-induced proliferation of T helper cells
      (CD4+) and B cells (CD19+) in the mouse lung tissue. Furthermore, treatment with
      E. japonicum extract modulated the expression of both T helper 2 cell-related
      factors [GATA binding protein 3 (GATA-3), tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-4, IL-5, IL-6 and IL-13], as well as that of T helper 1
      cell-related factors [(interferon-gamma (IFN-gamma), IL-12p35 and IL-12p40].
      These findings suggest that E. japonicum may potentially be used as an anti
      asthmatic treatment.

PMID- 27035742
TI  - Role of N-acetylgalactosaminyltransferase 6 in early tumorigenesis and formation
      of metastasis.
AB  - Glycosylation is one of the most important posttranslational modifications of
      proteins and lipids that contributes to the structural diversity of cellular
      molecules. Enzymes of the glycosyltransferase class are responsible for altering
      glycosylation patterns by adding carbohydrate chains to the respective acceptor
      molecules. It is well known that glycosylation is commonly altered in cancerous
      tissue. Therefore, the present study aimed to determine the incidence of N
      acetylgalactosaminyltransferase 6 (GALNT6), a prominent member of the
      glycosyltransferase class, in breast cancer tissue of different developmental
      stages by immunohistochemistry. Although no correlation was identified between
      tumour characteristics and GALNT6 staining intensity, to the best of our
      knowledge, this is the first study to demonstrate that tissue from carcinoma in
      situ-tumours and metastases were more heavily stained than late-stage breast
      cancers. This may indicate an important role of glycosylation aberration in
      escaping the immune system at early phases of tumour development. The present
      study also hypothesised that nascent or early metastasizing tumours are normally
      recognized by the immune system of the patient, but glycosylation pattern changes
      may facilitate tumor escape from immune recognition. In follow-up studies, our
      group will aim to confirm and consolidate these results in a larger patient
      cohort that may give greater insight into breast cancer characterization as well
      as tumour treatment. 

PMID- 27035743
TI  - Speech mapping using depth electrodes: The "electric Wada".
AB  - OBJECTIVES: The Wada test is the gold standard for identification of the side of
      speech dominance but is associated with risk of angiography and requires patient
      cooperation. We report a method to verify speech laterality using implanted
      electrodes in patients undergoing stereo-encephalography (SEEG). PATIENTS AND
      METHODS: Four pediatric patients with frontal lobe drug-resistant epilepsy
      underwent implantation of multiple SEEG electrodes using framed stereotaxy to
      identify the epileptogenic zone, including electrodes placed bilaterally into the
      pars opercularis of each inferior frontal gyrus from a superior parasagittal
      entry point. Biphasic stimulation at 50Hz, 0.3ms pulse width, up to 10mA was
      administered to distal contacts during a reading task. RESULTS: Speech arrest
      upon stimulation was obtained when stimulating distal contacts in the inferior
      frontal gyrus on one side with no effect on the contralateral side, establishing
      language laterality in every patient. This information was used to plan
      subsequent surgical treatment. There were no adverse events of implantation or
      stimulation. CONCLUSIONS: Brain mapping using SEEG electrodes is feasible and can
      be used to lateralize speech dominance. In cases of frontal lobe epilepsy in
      which electrodes will be implanted bilaterally for recording of ictal activity,
      this technique may make the Wada test unnecessary.

PMID- 27035744
TI  - Clinical Validation of Quantum Dot Barcode Diagnostic Technology.
AB  - There has been a major focus on the clinical translation of emerging technologies
      for diagnosing patients with infectious diseases, cancer, heart disease, and
      diabetes. However, most developments still remain at the academic stage where
      researchers use spiked target molecules to demonstrate the utility of a
      technology and assess the analytical performance. This approach does not account
      for the biological complexities and variabilities of human patient samples. As a
      technology matures and potentially becomes clinically viable, one important
      intermediate step in the translation process is to conduct a full clinical
      validation of the technology using a large number of patient samples. Here, we
      present a full detailed clinical validation of Quantum Dot (QD) barcode
      technology for diagnosing patients infected with Hepatitis B Virus (HBV). We
      further demonstrate that the detection of multiple regions of the viral genome
      using multiplexed QD barcodes improved clinical sensitivity from 54.9-66.7% to
      80.4-90.5%, and describe how to use QD barcodes for optimal clinical diagnosis of
      patients. The use of QDs in biology and medicine was first introduced in 1998 but
      has not reached clinical care. This study describes our long-term systematic
      development strategy to advance QD technology to a clinically feasible product
      for diagnosing patients. Our "blueprint" for translating the QD barcode research
      concept could be adapted for other nanotechnologies, to efficiently advance
      diagnostic techniques discovered in the academic laboratory to patient care.

PMID- 27035745
TI  - Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting
      PDCD4 in esophageal cancer.
AB  - Recent evidence indicates that exosomes can mediate certain microRNAs (miRNAs)
      involved in a series of biological functions in tumor occurrence and development.
      Our previous studies showed that microRNA-21 (miR-21) was abundant in both
      esophageal cancer cells and their corresponding exosomes. The present study
      explored the function of exosome-shuttling miR-21 involved in esophageal cancer
      progression. We found that exosomes could be internalized from the extracellular
      space to the cytoplasm. The exosome-derived Cy3-labeled miR-21 mimics could be
      transported into recipient cells in a neutral sphingomyelinase 2 (nSMase2)
      dependent manner. miR-21 overexpression from donor cells significantly promoted
      the migration and invasion of recipient cells by targeting programmed cell death
      4 (PDCD4) and activating its downstream c-Jun N-terminal kinase (JNK) signaling
      pathway after co-cultivation. Our population plasma sample analysis indicated
      that miR-21 was upregulated significantly in plasma from esophageal cancer
      patients and showed a significant risk association for esophageal cancer. Our
      data demonstrated that a close correlation existed between exosome-shuttling miR
      21 and esophageal cancer recurrence and distant metastasis. Thus, exosome
      shuttling miR-21 may become a potential biomarker for prognosis among esophageal
      cancer patients. 

PMID- 27035746
TI  - The effect of migration within the European Union/European Economic Area on the
      distribution of tuberculosis, 2007 to 2013.
AB  - Immigration from tuberculosis (TB) high-incidence countries is known to
      contribute notably to the TB burden in low-incidence countries. However, the
      effect of migration enabled by the free movement of persons within the European
      Union (EU)/European Economic Area (EEA) on TB notification has not been analysed.
      We analysed TB surveillance data from 29 EU/EEA countries submitted for the years
      2007-2013 to The European Surveillance System. We used place of birth and
      nationality as proxy indicators for native, other EU/EEA and non-EU/EEA origin of
      the TB cases and analysed the characteristics of the subgroups by origin. From
      2007-2013, a total of 527,467 TB cases were reported, of which 129,781 (24.6%)
      were of foreign origin including 12,566 (2.4%) originating from EU/EEA countries
      other than the reporting country. The countries reporting most TB cases
      originating from other EU/EEA countries were Germany and Italy, and the largest
      proportion of TB cases in individuals came from Poland (n=1,562) and Romania
      (n=6,285). At EU/EEA level only a small proportion of foreign TB cases originated
      from other EU/EEA countries, however, the uneven distribution of this presumed
      importation may pose a challenge to TB programmes in some countries. 

PMID- 27035747
TI  - Optimal combination of gemcitabine, sorafenib, and S-1 shows increased efficacy
      in treating cholangiocarcinoma in vitro and in vivo.
AB  - Cholangiocarcinoma (CCA) is one of the most difficult cancers to treat and lacks
      an established standard chemotherapy regimen. This study evaluated the effects of
      different combinations of gemcitabine, sorafenib, and S-1 on CCA cells to
      identify the optimal drug combination. A fractional factorial design method was
      applied in drug combination experiments to determine the optimal combination of
      these three drugs (gemcitabine=1.4 mmol/l, sorafenib=0.03 mmol/l, S-1=0.185
      mmol/l). We constructed a mathematical model with a small number of runs (Y=1.14
      0.377A-23.0B-1.81C+0.084A+109B+6.06C+3.83AB+0.175AC-40.4BC) to predict the
      efficacy of combinations of the drugs. The optimal combination can significantly
      inhibit the AKT/mTOR pathway, and thus CCA cell proliferation, and can induce
      cell apoptosis. In vivo, this combination (gemcitabine=1.4 mmol/l, sorafenib=0.03
      mmol/l, S-1=0.185 mmol/l) can significantly inhibit tumor growth. The present
      study showed that the mathematical model was reliable and could predict the
      efficacy of the different drug combinations. The optimal combination of these
      drugs may aid the development of a promising standard chemotherapy regimen for
      CCA.

PMID- 27035748
TI  - Antimicrobial resistance of Escherichia coli isolated in newly-hatched chickens
      and effect of amoxicillin treatment during their growth.
AB  - The use of antimicrobials in food animals is the major determinant for the
      propagation of resistant bacteria in the animal reservoir. However, other factors
      may also play a part, and in particular vertical spread between the generations
      has been suggested to be an important transmission pathway. The objective of this
      paper was to determine the resistance patterns of Escherichia coli isolated from
      newly-hatched chickens as well as to study the antibiotic pressure effect when
      amoxicillin was administered during their growing period. With this aim, meconium
      from 22 one-day-old Ross chickens was analysed. In addition, during their growth
      period, amoxicillin treatments at days 7, 21 and 35 were carried out. Results
      showed a high number of E. coli-resistant strains were isolated from the treated
      one-day-old chickens, and were the highest for beta-lactams group, followed by
      quinolone and tetracyclines. After treatment with amoxicillin, the highest
      percentage of resistances were detected for this antibiotic compared to the
      others analysed, with significant differences in resistance percentages between
      control and treated broilers detected in relation to ampicillin, cephalothin,
      streptomycin, kanamycin, gentamicin, chloramphenicol and tetracycline.
      Differences in resistances to ciprofloxacin and nalidixic acid between control
      and treated animals were not observed and there was lack of resistance for
      amikacin and ceftriaxone. These results suggest the possibility of vertical
      transmission of resistant strains to newly-hatched chicks from parent flocks, and
      seem to indicate that the treatment with amoxicillin increased the resistance of
      E. coli to other antibiotics. 

PMID- 27035749
TI  - Circadian clock gene Per2 plays an important role in cell proliferation,
      apoptosis and cell cycle progression in human oral squamous cell carcinoma.
AB  - Previous studies have shown that the aberrant expression of period circadian
      clock 2 (Per2) is closely related to the occurrence and development of cancers,
      but the specific mechanism remains unclear. In the present study, we used shRNA
      to downregulate Per2 in oral squamous cell carcinoma (OSCC) Tca8113 cells, and
      then detected the alterations in cell cycle, cell proliferation and apoptosis by
      flow cytometric analysis and mRNA expression alterations in all the important
      genes in the cyclin/cyclin-dependent protein kinase (CDK)/cyclin-dependent kinase
      inhibitor (CKI) cell cycle network by RT-qPCR. We found that in the Tca8113
      cells, after Per2 downregulation, the mRNA expression levels of cyclin A2, B1 and
      D1, CDK4, CDK6 and E2F1 were significantly increased (P<0.05), the mRNA
      expression levels of p53, p16 and p21 were significantly decreased (P<0.05), cell
      proliferation was significantly higher (P<0.05), apoptosis was significantly
      lower (P<0.05) and the number of cells in the G1/G0 phase was significantly
      decreased (P<0.05). The present study proves that in OSCC, clock gene Per2 plays
      an important role in cell cycle progression and the balance of cell proliferation
      and apoptosis by regulation of the cyclin/CDK/CKI cell cycle network. Further
      research on Per2 may provide a new effective molecular target for cancer
      treatments. 

PMID- 27035750
TI  - CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer
      MCF-7 cells.
AB  - Claudin 6 (CLDN6), a member of tight junction protein claudin (CLDN) family,
      inhibits proliferation and induces apoptosis of MCF-7 breast cancer cells.
      However, these molecular mechanisms of CLDN6-induced apoptosis remain largely
      elusive. We previously found that restoration of human CLDN6 gene expression was
      correlated with the expression level of apoptosis signal-regulating kinase 1
      (ASK1) using cDNA array and bioinformatics analysis. ASK1, a mitogen-activated
      protein kinase kinase kinase, is involved in environmental stress-activation of
      the c-jun N-terminal kinase (JNK) and p38 pathways, which contribute to apoptosis
      associated tumor cell death. In the present study, we show that the restoration
      of CLDN6 gene expression in MCF-7 cells marhedly decreased ASK1 phosphorylation
      at Ser967. Activated ASK1ser967 further induced the activation of downstream
      targets, JNK and p38 kinase. MCF-7/CLDN6 stable transfection cell clone treated
      with TRX1, an ASK1 inhibitor, showed suppressed JNK and p38 activation, and
      showed substantially increased survival and colony formation and reduced percent
      of apoptotic cells using TUNEL staining and DNA ladder. Furthermore, TRX1
      treatment increased Bcl-2/Bax ratio and reduced caspase-3 cleavage in MCF-7/CLDN6
      stable transfection cell clone. Therefore, these data show that CLDN6 mediates
      ASK1-p38/JNK apoptotic signaling in MCF-7 cells, and it is correlated with
      constitutive deregulation of the balance of Bcl-2 family proteins and activation
      of caspase-3. 

PMID- 27035751
TI  - Development and application of a rapid and visual loop-mediated isothermal
      amplification for the detection of Sporisorium scitamineum in sugarcane.
AB  - Smut is a fungal disease with widespread prevalence in sugarcane planting areas.
      Early detection and proper identification of Sporisorium scitamineum are
      essential in smut management practices. In the present study, four specific
      primers targeting the core effector Pep1 gene of S. scitamineum were designed.
      Optimal concentrations of Mg(2+), primer and Bst DNA polymerase, the three
      important components of the loop-mediated isothermal amplification (LAMP)
      reaction system, were screened using a single factor experiment method and the
      L16(4(5)) orthogonal experimental design. Hence, a LAMP system suitable for
      detection of S. scitamineum was established. High specificity of the LAMP method
      was confirmed by the assay of S. scitamineum, Fusarium moniliforme, Pestalotia
      ginkgo, Helminthospcrium sacchari, Fusarium oxysporum and endophytes of Yacheng05
      179 and ROC22. The sensitivity of the LAMP method was equal to that of the
      conventional PCR targeting Pep1 gene and was 100 times higher than that of the
      conventional PCR assay targeting bE gene in S. scitamineum. The results suggest
      that this novel LAMP system has strong specificity and high sensitivity. This
      method not only provides technological support for the epidemic monitoring of
      sugarcane smut, but also provides a good case for development of similar
      detection technology for other plant pathogens. 

PMID- 27035752
TI  - Endogenous hydrogen sulfide is involved in osteogenic differentiation in human
      periodontal ligament cells.
AB  - OBJECTIVE: Endogenous hydrogen sulfide (H2S) has recently emerged as an important
      intracellular gaseous signaling molecule within cellular systems. Endogenous H2S
      is synthesized from l-cysteine via cystathionine beta-synthase and cystathionine
      gamma-lyase and it regulates multiple signaling pathways in mammalian cells.
      Indeed, aberrant H2S levels have been linked to defects in bone formation in
      experimental mice. The aim of this study was to examine the potential production
      mechanism and function of endogenous H2S within primary human periodontal
      ligament cells (PDLCs). DESIGN: Primary human PDLCs were obtained from donor
      molars with volunteer permission. Immunofluorescent labeling determined
      expression of the H2S synthetase enzymes. These enzymes were inhibited with D,L
      propargylglycine or hydroxylamine to examine the effects of H2S signaling upon
      the osteogenic differentiation of PDLCs. Gene and protein expression levels of
      osteogenic markers in conjunction with ALP staining and activity and alizarin red
      S staining of calcium deposition were used to assay the progression of
      osteogenesis under different treatment conditions. Cultures were exposed to Wnt3a
      treatment to assess downstream signaling mechanisms. RESULTS: In this study, we
      show that H2S is produced by human PDLCs via the cystathionine beta
      synthase/cystathionine gamma-lyase pathway to promote their osteogenic
      differentiation. These levels must be carefully maintained as excessive or
      deficient H2S levels temper the observed osteogenic effect by inhibiting Wnt/beta
      catenin signaling. CONCLUSIONS: These results demonstrate that optimal
      concentrations of endogenous H2S must be maintained within PDLCs to promote
      osteogenic differentiation by activating the Wnt/beta-catenin signaling cascade.

PMID- 27035753
TI  - A Local CC2 and TDA-DFT Double Hybrid Study on BODIPY/aza-BODIPY Dimers as Heavy
      Atom Free Triplet Photosensitizers for Photodynamic Therapy Applications.
AB  - A series of 11 different boron-dipyrromethene (BODIPY) dimers is carefully
      examined by means of ab initio and Tamm-Dancoff approximated density functional
      theory methods. Vertical and 0-0 excitation energies along with the tetraradical
      character of these dimers are determined. Possible application of a series of
      linked dimers for photodynamic therapy (PDT) was investigated through computing
      their excitation energies, spin-orbit coupling matrix elements, and singlet
      triplet energy gaps. Finally through a systematic investigation of a series of 36
      different BODIPY and aza-BODIPY dimers, a new class of near-IR heavy atom free
      photosensitizers for PDT action is introduced.

PMID- 27035754
TI  - Switchable probes: pH-triggered and VEGFR2 targeted peptides screening through
      imprinting microarray.
AB  - One switchable affinity peptide, STP, is screened out from a high-throughput
      library by an integrated imprinting microarray. STP is pH triggered and also the
      ligand of the marker VEGFR2. Efficient cell recognition and penetration as well
      as an in vivo image could be "turned on" and accelerated only in the condition of
      VEGFR2 overexpression and a mild acidic environment. 

PMID- 27035755
TI  - Podoplanin-mediated TGF-beta-induced epithelial-mesenchymal transition and its
      correlation with bHLH transcription factor DEC in TE-11 cells.
AB  - Podoplanin is reported involved in the collective cell invasion, another tumor
      invasion style which is distinct from the single cell invasion, so-called
      epithelial-mesenchymal transition (EMT). In this study, we investigated the
      correlation between podoplanin and EMT-related markers in esophageal squamous
      cell carcinoma (ESCC), and evaluated its linkage with the basic helix-loop-helix
      (bHLH) transcription factor differentiated embryonic chondrocyte (DEC) 1 and
      DEC2. Three ESCC cell lines and human squamous cell carcinoma A431 cells were
      subjected to western blot analyses for podoplanin and EMT markers, as well as the
      expression of DEC1 and DEC2. By RT-qPCR and western blotting, we found that TGF
      beta increased the expression of podoplanin and mensenchymal markers (e.g., N
      cadherin and vimentin), while decreased the expression of epithelial markers
      (e.g., Claudin-4 and E-cadherin), accompanied by Smad2 phosphorylation and slug
      activation. Moreover, TGF-beta has different effects on the expression of DEC1
      and DEC2, that is, it upregulates DEC1, but downregulates DEC2. Capability of
      cell proliferation, invasion and migration were further analyzed using CCK-8
      assay, Matrigel-invasion assay, and the wound-healing assay, respectively. The
      proliferation, invasion and migration ability were significantly lost in
      podoplanin-knockdown cells when compared with the scrambled siRNA group. In
      addition to these changes, the expression of Claudin-4, but not that of Claudin-1
      or E-cadherin, was induced by the siRNA against podoplanin. On the contrary,
      overexpression of DEC1 and DEC2 exhibits opposite effects on podoplanin, but only
      slight effect on Claudin-4 was detected. These data indicated that podoplanin is
      significantly associated with EMT of TE-11 cells, and may be directly or
      indirectly regulated by bHLH transcription factors DEC1 and DEC2. 

PMID- 27035756
TI  - Sulforaphane promotes immune responses in a WEHI-3-induced leukemia mouse model
      through enhanced phagocytosis of macrophages and natural killer cell activities
      in vivo.
AB  - Sulforaphane (SFN) is an isothiocyanate, inducing cytotoxic effects in various
      human cancer cells, including leukemia cells through cell cycle arrest and
      apoptosis. However, the effect of SFN on the immune responses in a leukemia mouse
      model remains to be investigated. The present study investigated whether SFN has
      an effect on the immune responses in a WEHI-3-induced leukemia mouse model in
      vivo. Normal BALB/c mice were injected with WEHI-3 cells to generate the leukemia
      mouse model, and were subsequently treated with placebo or SFN (0, 285, 570 and
      1,140 mg/kg) for 3 weeks. Following treatment, all mice were weighted and blood
      samples were collected. In addition, liver and spleen samples were isolated to
      determine cell markers, phagocytosis and natural killer (NK) cell activities, and
      cell proliferation was examined using flow cytometry. The results indicated that
      SFN treatment had no significant effect on the spleen weight, however it
      decreased liver and body weight. Furthermore, SFN treatment increased the
      percentage levels of CD3 (T cells) and CD19 (B cell maker), however had no effect
      on the levels of CD11b (monocytes) or Mac-3 (macrophages), compared with the WEHI
      3 control groups. The administration of SFN increased the phagocytosis of
      macrophages from peripheral blood mononuclear cells and peritoneal cavity, and
      increased the activity of NK cells from splenocytes. Administration of SFN
      promoted T and B cell proliferation following stimulation with concanavalin A and
      lipopolysaccharide, respectively. 

PMID- 27035757
TI  - Disrupted intestinal structure in a rat model of intermittent hypoxia.
AB  - Obstructive sleep apnea (OSA) is a chronic condition characterized by chronic
      intermittent hypoxia (IH) and subsequent reoxygenation (ROX). The
      gastrointestinal system, which is particularly sensitive to tissue hypoxia and
      reduced perfusion, is likely to be affected by OSA. A rat model of IH was used to
      analyze oxidative stress-associated genes and tight junction proteins by reverse
      transcription-quantitative polymerase chain reaction. Subsequently, altered
      morphology of the duodenal mucosa and elevated Chiu scores were observed in the
      IH-exposed rats. In addition, IH exposure resulted in upregulation of the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, NADPH
      oxidase 2 and p22phox, in the small intestine, and upregulation of transcription
      factors, including hypoxia-inducible factor-1, nuclear factor-kappaB and
      activator protein-1. Furthermore, the mRNA expression levels of intestinal tight
      junction (TJ)-related proteins, claudin-1 and claudin-4, were decreased in the IH
      exposed group, as compared with in the control group. In conclusion, the present
      study demonstrated that OSA, which is characterized by IH and ROX, may lead to
      disruption of the duodenum. The mechanism underlying the effects of OSA on
      duodenal morphology may be associated with increased oxidative stress and
      activation of transcription factors, subsequently inducing intestinal TJ
      disruption and intestinal injury. 

PMID- 27035758
TI  - Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care
      units: a systematic review.
AB  - BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often
      requires potentially invasive or uncomfortable procedures, such as mechanical
      ventilation (MV). Sedation can alleviate pain and discomfort, provide protection
      from stressful or harmful events, prevent anxiety and promote sleep. Various
      sedative agents are available for use in ICUs. In the UK, the most commonly used
      sedatives are propofol (Diprivan((r)), AstraZeneca), benzodiazepines [e.g.
      midazolam (Hypnovel((r)), Roche) and lorazepam (Ativan((r)), Pfizer)] and alpha-2
      adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor((r)), Orion
      Corporation) and clonidine (Catapres((r)), Boehringer Ingelheim)]. Sedative
      agents vary in onset/duration of effects and in their side effects. The pattern
      of sedation of alpha-2 agonists is quite different from that of other sedatives
      in that patients can be aroused readily and their cognitive performance on
      psychometric tests is usually preserved. Moreover, respiratory depression is less
      frequent after alpha-2 agonists than after other sedative agents. OBJECTIVES: To
      conduct a systematic review to evaluate the comparative effects of alpha-2
      agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines
      (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.
      DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without
      revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane
      Central Register of Controlled Trials) from 1999 to 2014. METHODS: Evidence was
      considered from randomised controlled trials (RCTs) comparing dexmedetomidine
      with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines
      such as midazolam, lorazepam and diazepam (Diazemuls((r)), Actavis UK Limited).
      Primary outcomes included mortality, duration of MV, length of ICU stay and
      adverse events. One reviewer extracted data and assessed the risk of bias of
      included trials. A second reviewer cross-checked all the data extracted. Random
      effects meta-analyses were used for data synthesis. RESULTS: Eighteen RCTs (2489
      adult patients) were included. One trial at unclear risk of bias compared
      dexmedetomidine with clonidine and found that target sedation was achieved in a
      higher number of patients treated with dexmedetomidine with lesser need for
      additional sedation. The remaining 17 trials compared dexmedetomidine with
      propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably
      with regard to clinical population, type of comparators, dose of sedative agents,
      outcome measures and length of follow-up. Overall, risk of bias was generally
      high or unclear. In particular, few trials blinded outcome assessors. Compared
      with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no
      significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval
      (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference 
      1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to
      extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p
      < 0.00001) were significantly shorter among patients who received
      dexmedetomidine. No difference in time to target sedation range was observed
      between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was
      associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2)
      = 46%; p = 0.001). LIMITATIONS: Trials varied considerably with regard to
      participants, type of comparators, dose of sedative agents, outcome measures and
      length of follow-up. Overall, risk of bias was generally high or unclear. In
      particular, few trials blinded assessors. CONCLUSIONS: Evidence on the use of
      clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing
      ICU length of stay and time to extubation in critically ill ICU patients. Risk of
      bradycardia but not of overall mortality is higher among patients treated with
      dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in
      ICUs and identify subgroups of patients that are more likely to benefit from the
      use of dexmedetomidine. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42014014101. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme. The Health Services Research Unit is core funded
      by the Chief Scientist Office of the Scottish Government Health and Social Care
      Directorates.

PMID- 27035759
TI  - MicroRNA-194 restrains the cell progression of non-small cell lung cancer by
      targeting human nuclear distribution protein C.
AB  - NSCLC accounts for over 80% of all lung cancers and is associated with poor
      prognosis. Human nuclear distribution C (hNUDC) was predicted to be the target
      gene of microRNA-194 (miR-194). The present study was designed to demonstrate the
      mechanism of miR-194 in the regulation of non-small cell lung cancer (NSCLC) via
      targeting the hNUDC. The hNUDC expression was found to strongly be increased
      while the miR-194 decreased significantly in the NSCLC cell lines when compared
      with the healthy controls. Moreover, the luciferase report confirmed the
      targeting reaction between miR-194 and hNUDC. After transfection with miR-194
      mimic into NSCLC cells, we found that the miR-194 overexpression resulted in
      abnormal nuclear division, decreased cell proliferation and inhibited the
      expression of hNUDC and Mpl/ERK pathway proteins. Furthermore, the hNUDC
      overexpression affected the suppression effect of miR-194 in 95D cells,
      indicating that miR-194 suppresses tumor cell process by inhibiting the hNUDC
      expression. In brief, the present study suggests that the upregulation of miR-194
      affects the hNUDC expression, leading to a downregulated expression of Mpl/ERK
      pathway proteins, and suppresses the mitosis and proliferation of NSCLC cells.
      These results offer a potential therapeutic strategy for the treatment of lung
      cancer. 

PMID- 27035760
TI  - Mesenchymal stem cells ameliorate inflammatory cytokine-induced impairment of AT
      II cells through a keratinocyte growth factor-dependent PI3K/Akt/mTOR signaling
      pathway.
AB  - Lung epithelium restoration subsequent to injury is of concern in association
      with the outcomes of diverse inflammatory lung diseases. Previous studies have
      demonstrated that mesenchymal stem cells (MSCs) may promote epithelial repair
      subsequent to inflammatory injury, however the mechanism that mediates this
      effect remains unclear. The current study examined the role of MSCs in alveolar
      type II epithelial cell (AT-II cell) restoration subsequent to an inflammatory
      insult. AT-II cells were firstly exposed to inflammatory cytokines including
      tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1beta, then were co
      cultured with MSCs in Transwell for 72 h. Cell proliferation, expression of
      surfactant protein A (SP-A) and expression of the alpha1 subunit were evaluated
      respectively by the Cell Counting Kit-8 assay, western blotting and
      semiquantitative reverse transcription-polymerase chain reaction. Keratinocyte
      growth factor (KGF) small interfering RNA (siRNA) was applied to knockdown the
      main cytoprotective factors in the MSCs. Subsequent to an inflammatory insult, AT
      II cells were observed to be impaired, exhibiting the characteristics of injured
      cell morphology, reduced cell proliferation and reduced expression of SP-A and
      the alpha1 subunit. Co-culture with MSCs significantly ameliorated these cell
      impairments, while these benefits were weakened by the application of KGF siRNA.
      Simultaneously, expression levels of phosphorylated (p-) protein kinase B (AKT)
      and p-mammalian target of rapamycin (mTOR) in AT-II cells were upregulated by
      MSCs, suggesting activation of the phosphoinositide 3-kinase (PI3K) pathway.
      These data demonstrate that administration of MSCs to the inflammation-insulted
      AT-II cells may ameliorate the impairments through a KGF-dependent PI3K/AKT/mTOR
      signaling pathway. 

PMID- 27035761
TI  - Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated
      Nanodroplets.
AB  - We have developed a method for super-resolution ultrasound imaging, which relies
      on a new class of blinking nanometer-size contrast agents: laser-activated
      nanodroplets (LANDs). The LANDs can be repeatedly optically triggered to undergo
      vaporization; the resulting spatially stationary, temporally transient
      microbubbles provide high ultrasound contrast for several to hundreds of
      milliseconds before recondensing to their native liquid nanodroplet state. By
      capturing high frame rate ultrasound images of blinking LANDs, we demonstrate the
      ability to detect individual recondensation events. Then we apply a newly
      developed super-resolution image processing algorithm to localize the LAND
      positions in vivo almost an order of magnitude better than conventional
      ultrasound imaging. These results pave the way for high resolution molecular
      imaging deep in tissue. 

PMID- 27035762
TI  - Hydrophobically Tailored Carbon Dots toward Modulating Microstructure of Reverse
      Micelle and Amplification of Lipase Catalytic Response.
AB  - This article delineates the modulation of microstructure of cationic reverse
      micelle utilizing hydrophobically modified carbon dots (CDs) with varying surface
      functionalizations. Citric acid was used as the source of the carbon core, and Na
      salt of glycine, glycine, Na-salt of 11-aminoundecanoic acid, 11-aminoundecanoic
      acid, and n-hexadecylamine were used for the surface fabrication of CDs to
      produce CD 1s, CD 1a, CD 2s, CD 2a, and CD 3, respectively. All these CDs having
      dimension of 5-7 nm were characterized by spectroscopic and microscopic
      techniques. The hydrodynamic diameter of cetyltrimethylammonium bromide (CTAB)
      reverse micelle (CTAB/isooctane/n-hexanol/water) at z
      ([cosurfactant]/[surfactant]) = 6.4 and W0 ([water]/[surfactant]) = 44 is around
      15-20 nm. Interestingly, the size of the water-in-oil (w/o) microemulsions
      dramatically increased up to 120-200 nm upon doping hydrophobic surface
      functionalized CD 2a and CD 3. This is possibly due to change in the micellar
      exchange dynamics and reorganization of the micellar aggregates via hydrophobic
      interaction between surfactant (CTAB) tail and hydrophobic surface modifier of
      the carbon dots. However, no alteration in the size of reverse micelles was noted
      in the presence of carbon dots CD 1s, CD 1a, and CD 2s. Spectroscopic and
      microscopic investigations confirmed that the hydrophobic CD 2a and CD 3 were
      localized at the interface of reverse micelles whereas CD 1s, CD 1a, and CD 2s
      were possibly located in the water pool (away from interface). The activity of
      Chromobacterium viscosum lipase encapsulated within CD 3 and CD 2a doped
      significantly large CTAB reverse micelles showed remarkable improvement (3.7-fold
      and 3.4-fold) in its catalytic response. However, hydrophilic carbon dots CD 1s
      and CD 2s as well as moderately hydrophobic CD 1a had no significant effect on
      the microstructure of reverse micelles as well as on the lipase activity.

PMID- 27035763
TI  - The cost of parallel consolidation into visual working memory.
AB  - A growing body of evidence indicates that information can be consolidated into
      visual working memory in parallel. Initially, it was suggested that color
      information could be consolidated in parallel while orientation was strictly
      limited to serial consolidation (Liu & Becker, 2013). However, we recently found
      evidence suggesting that both orientation and motion direction items can be
      consolidated in parallel, with different levels of accuracy (Rideaux, Apthorp, &
      Edwards, 2015). Here we examine whether there is a cost associated with parallel
      consolidation of orientation and direction information by comparing performance,
      in terms of precision and guess rate, on a target recall task where items are
      presented either sequentially or simultaneously. The results compellingly
      indicate that motion direction can be consolidated in parallel, but the evidence
      for orientation is less conclusive. Further, we find that there is a twofold cost
      associated with parallel consolidation of direction: Both the probability of
      failing to consolidate one (or both) item/s increases and the precision at which
      representations are encoded is reduced. Additionally, we find evidence indicating
      that the increased consolidation failure may be due to interference between items
      presented simultaneously, and is moderated by item similarity. These findings
      suggest that a biased competition model may explain differences in parallel
      consolidation between features. 

PMID- 27035764
TI  - MicroRNA-205 acts as a tumor suppressor in osteosarcoma via targeting RUNX2.
AB  - MicroRNAs (miRs) are a class of small non-coding RNAs, and negatively regulate
      gene expression through directly binding to the 3'-untranslational region (UTR)
      of their target mRNA, which further leads to translational repression or mRNA
      degradation. Recently, various miRs have been implicated in the development and
      progression of osteosarcoma (OS). However, the underlying mechanism has not been
      fully uncovered. Our study aimed to reveal the exact role of miR-205 in OS, as
      well as the regulatory mechanism. In this study, we found that the expression of
      miR-205 was significantly reduced in a total of 34 OS tissue specimens compared
      to their matched adjacent normal tissues. Besides, it was also remarkably
      downregulated in OS cell lines (Saos-2, U2OS, SW1353, and MG63) compared to human
      osteoblast hFOB1.19 cells. Overexpression of miR-205 caused a significant
      decrease in the proliferation, migration and invasion of MG63 and U2OS cells.
      Runt-related transcription factor 2 (RUNX2) was further identified as a target
      gene of miR-205. Moreover, the mRNA and protein expression of RUNX2 was reduced
      after miR-205 overexpression, but increased after knockdown of miR-205 in MG63
      and U2OS cells. Furthermore, overexpression of RUNX2 effectively reversed the
      suppressive effect of miR-205 on the proliferation, migration, and invasion of
      MG63 and U2OS cells. The RUNX2 level was significantly increased in OS tissues
      compared to their matched adjacent normal tissues, as well as in OS cell lines
      compared to hFOB1.19 cells. In addition, the RUNX2 level was reversely correlated
      with the miR-205 level in OS tissues. Taken together, our data demonstrate that
      miR-205 acts as a tumor suppressor in OS via directly targeting RUNX2. Therefore,
      we suggest that the miR-205/RUNX2 axis may serve as a potential target for the
      treatment of OS. 

PMID- 27035765
TI  - IL-6 and IL-8 enhance factor H binding to the cell membranes.
AB  - The aim of the present study was to assess the role of interleukin (IL)-6 and IL
      8 on the expression of fluid-phase complement inhibitor, factor H (FH), and FH
      like protein 1 (FHL-1), in the A2780 ovarian carcinoma cell line. This cell line
      does not normally produce IL-6, however, is IL-6 responsive due to the presence
      of receptor for IL-6. The presence of FH and FHL-1 in the cell lysates was
      confirmed by western blotting. The levels of FH and FHL-1 in the medium were
      determined by enzyme-linked immunosorbent assay. To evaluate gene expression,
      reverse transcription-quantitative polymerase chain reaction was performed. The
      cellular localization of FH and FHL-1 in ovarian cancer cells was assessed by
      immunofluorescence. The present study revealed that FH, contrary to FHL-1, was
      secreted by ovarian cancer cells, however, this process was independent of IL
      stimulation. No significant differences were observed in the concentration of FH
      in the control cells, when compared with the samples treated with IL-6/IL-8. The
      results of western blotting revealed that the protein expression levels of FH and
      FHL-1 were not regulated by IL-6 and IL-8 in a dose-dependent manner.
      Immunofluorescence analysis confirmed that the A2780 ovarian cancer cell line
      expressed both membrane bound and intracellular forms of FH and FHL-1. The
      present data revealed that the A2780 cells expressed and secreted FH protein and
      are also able to bind FH and FHL-1. This may influence the efficiency of
      complement mediated immunotherapy. 

PMID- 27035766
TI  - Expression of trophinin and dipeptidyl peptidase IV in endometrial co-culture in
      the presence of an embryo: A comparative immunocytochemical study.
AB  - Recurrent implantation failure leads to a reduced pregnancy rate. The expression
      patterns of trophinin and dipeptidyl peptidase IV (CD26) indicate the involvement
      of embryo implantation and early placental development. The purpose of the
      present study was to evaluate endometrial co-culture cells in the presence of
      embryo with trophinin and CD26 immunofluorescence staining. Patients with
      recurrent implantation failure were enrolled in the present study. The patients
      were aged between 26 and 36 years. Co-cultures were prepared from endometrial
      biopsies for each patient. Controlled ovarian hyperstimulation was performed on
      each of the patients. Certain embryos were maintained in a conventional culture
      environment (n=80), and others in an endometrial co-culture environment (n=25).
      Following embryo transfer, the co-culture cells were examined under an inverted
      wide-field fluorescence microscope. The ratio of a successful pregnancy was 0.38
      in the present study (n=5/13 pregnancies). The average age of the successful
      group (28+/-3.54 years) was younger compared with the unsuccessful (32.67+/-2.81)
      group (P<=0.05). The number of trophinin (+) endometrial cells in the presence of
      an embryo was significantly lower (P=0.046) in the successful group on the first
      day. No significant difference between the groups was observed in terms of the
      number of CD26 (+) cells on the first to the fourth days (P<=0.05). Trophinin and
      CD26 immunostaining is important in the early period of pregnancy, and it will be
      beneficial in terms of providing the deficit of conventional culture medium in
      performed studies with the endometrial co-culture medium. The co-culture may be
      important, particularly in the early period, in patients with recurrent
      implantation failure in terms of enabling a connection between the cells
      belonging to the endometrium and the embryo. 

PMID- 27035767
TI  - Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative
      stress in spontaneously hypertensive rats.
AB  - Fibulin-3 has been suggested to function in the remodeling of the extracellular
      matrix, however its role remains unclear in hypertensive vascular remodeling. In
      the current study, 10 Wistar-Kyoto (WKY) rats (control group) and 30
      spontaneously hypertensive rats (SHRs) were used. SHRs were randomized into three
      groups: The placebo group, intravenous (I.V.) physiological saline; the FBLN-1
      group, low-dose fibulin-3 protein (I.V.; 120 ng/kg); and the FBLN-2 group, high
      dose fibulin-3 protein (I.V.; 240 ng/kg). Histological analysis was used to
      analyze vascular remodeling. The expression of fibulin-3, matrix
      metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)
      3 were detected by immunohistochemistry, western blotting and reverse
      transcription-quantitative polymerase chain reaction. Oxidative stress was
      detected by dihydroethidium staining. The systolic blood pressure (SBP) of SHRs
      was observed to be significantly greater than that of WKY rats (P<0.05). SBP in
      the FBLN-2 group was significantly reduced compared with the placebo group (182+/
      12 mmHg vs. 224+/-14 mmHg; P<0.05). The thoracic aortic wall thickness in the SHR
      groups (placebo group, FBLN-1 group and FBLN-2 group) was observed to tbe
      significantly thicker than in the control group (P<0.01). The wall thickness of
      the FBLN-2 group was significantly greater than that of the placebo and FBLN-1
      groups (124.2+/-11.8 um vs. 106.9+/-9.5 um and 96.8+/-10.2 um; P<0.05). The wall
      to-lumen ratios of the placebo, FBLN-1 and FBLN-2 groups were significantly
      greater than that of the control group (P<0.05). In addition, the expression
      levels of fibulin-3 and MMP-2/9 at protein and mRNA levels were significantly
      increased in the thoracic aorta of the placebo group compared with the control
      group (P<0.05). The levels of MMP-2/9 were significantly reduced in the FBLN-2
      group compared with the placebo group (P<0.05). Levels of TIMP-3 however,
      exhibited no significant differences in the four groups (P>0.05). Reactive oxygen
      species (ROS) were increased in the placebo group vs. the control group. Fibulin
      3 was able to alleviate the levels of ROS in the FBLN groups. It is suggested
      that fibulin-3 may act as a growth factor in the arteries. In addition, the
      results indicated that fibulin-3 may reduce the levels of MMP-2 and -9 and
      oxidative stress in hypertensive vascular remodeling. Upregulating fibulin-3 may
      be beneficial for improving vascular health and offsetting certain cardiovascular
      risk factors of hypertension. 

PMID- 27035768
TI  - Clustering Suicide Attempters: Impulsive-Ambivalent, Well-Planned, or Frequent.
AB  - BACKGROUND: Attempts to predict suicidal behavior within high-risk populations
      have so far shown insufficient accuracy. Although several psychosocial and
      clinical features have been consistently associated with suicide attempts,
      investigations of latent structure in well-characterized populations of suicide
      attempters are lacking. METHODS: We analyzed a sample of 1,009 hospitalized
      suicide attempters that were recruited between 1999 and 2012. Eleven clinically
      relevant items related to the characteristics of suicidal behavior were submitted
      to a Hierarchical Ascendant Classification. Phenotypic profiles were compared
      between the resulting clusters. A decisional tree was constructed to facilitate
      the differentiation of individuals classified within the first 2 clusters.
      RESULTS: Most individuals were included in a cluster characterized by less lethal
      means and planning ("impulse-ambivalent"). A second cluster featured more
      carefully planned attempts ("well-planned"), more alcohol or drug use before the
      attempt, and more precautions to avoid interruptions. Finally, a small, third
      cluster included individuals reporting more attempts ("frequent"), more often
      serious or violent attempts, and an earlier age at first attempt. Differences
      across clusters by demographic and clinical characteristics were also found,
      particularly with the third cluster whose participants had experienced high
      levels of childhood abuse. CONCLUSIONS: Cluster analysis consistently supported 3
      distinct clusters of individuals with specific features in their suicidal
      behaviors and phenotypic profiles that could help clinicians to better focus
      prevention strategies.

PMID- 27035769
TI  - Bisphenols Come in Different Flavors: Is "S" Better Than "A"?

PMID- 27035770
TI  - Bisphenol A Effects on Gonadotroph Function: Disruption of Pituitary Cell-Cell
      Communication?

PMID- 27035771
TI  - Differential Hepatic Gene Expression Profile and Histone Modification After Acute
      or Chronic Hyperthyroidism or During Remission.

PMID- 27035774
TI  - Ultra-thin film composite mixed matrix membranes incorporating iron(III)-dopamine
      nanoparticles for CO2 separation.
AB  - Iron dopamine nanoparticles (FeDA NPs) are incorporated into a nanoscale thick
      polyethylene glycol (PEG) matrix for the first time, to form ultra-thin film
      composite mixed matrix membranes (UTFC-MMMs) via a recently developed continuous
      assembly of polymers (CAP) nanotechnology. The FeDA NPs are prepared by in situ
      nano-complexation between Fe(3+) and DA and have a particle size that can be
      varied from 3 to 74 nanometers by adjusting the molar ratio of DA to Fe(3+) ion.
      The cross-linked selective layer with sub 100 nanometer thickness is prepared by
      atom transfer radical polymerisation of a mixture of PEG macrocross-linkers and
      FeDA NPs on top of a highly permeable poly(dimethyl siloxane) (PDMS) prelayer,
      which is spin-coated onto a porous polyacrylonitrile (PAN) substrate. The
      incorporation of the FeDA NPs within the PEG-based selective layer is confirmed
      by XPS analysis. The UTFC-MMMs (thickness: ~45 nm) formed present excellent gas
      separation performance with a CO2 permeance of ~1200 GPU (1 GPU = 10(-6) cm(3)
      (STP) cm(-2) s(-1) cmHg(-1)) and an enhanced CO2/N2 selectivity of over 35, which
      is the best performance for UTFC membranes in the reported literature. 

PMID- 27035775
TI  - Chronic Obstructive Pulmonary Disease: When Pulmonologists Do Something Good for
      the Heart.

PMID- 27035776
TI  - Spirometry in Chronic Obstructive Pulmonary Disease. From Rule of Thumb to
      Science.

PMID- 27035777
TI  - Bone Loss in the Intensive Care Unit.

PMID- 27035778
TI  - Cryobiopsy in the Diagnosis of Interstitial Lung Disease. A Step Forward or Back?

PMID- 27035779
TI  - Diffusing Capacity in Bronchopulmonary Dysplasia. Can Function Determine
      Structure?

PMID- 27035780
TI  - An Expression of Clinical Significance: Exploring the Human Genome to Understand
      the Variable Response to Rhinovirus.

PMID- 27035781
TI  - Does Age Matter? The Relationship between Sleep-disordered Breathing and Incident
      Atrial Fibrillation in Older Men.

PMID- 27035782
TI  - An American Thoracic Society Official Research Statement: Future Directions in
      Lung Fibrosis Research.
AB  - BACKGROUND: Pulmonary fibrosis encompasses a group of lung-scarring disorders
      that occur owing to known or unknown insults and accounts for significant
      morbidity and mortality. Despite intense investigation spanning decades, much
      remains to be learned about the natural history, pathophysiology, and biologic
      mechanisms of disease. PURPOSE: To identify the most pressing research needs in
      the lung fibrosis community and to provide a roadmap of priorities to
      investigators, funding agencies, patient advocacy groups, and other interested
      stakeholders. METHODS: An ad hoc international working group of the American
      Thoracic Society with experience in clinical, translational, and bench-based
      research in fibrotic lung diseases was convened. The group used an iterative
      consensus process to identify successes and challenges in pulmonary fibrosis
      research. MEASUREMENTS AND MAIN RESULTS: The group identified five main priority
      areas in which substantial resources should be invested to advance our
      understanding and to develop novel therapies for patients with pulmonary
      fibrosis. These priorities include develop newer models of human lung fibrosis,
      engage current and new stakeholders to provide sustained funding for the
      initiatives, create a global infrastructure for storing patient-derived
      materials, establish collaborative preclinical and clinical research networks in
      fibrotic lung disease, and create a global lung fibrosis initiative that unites
      these multifaceted efforts into a single virtual umbrella structure. CONCLUSIONS:
      Despite recent advances in the treatment of some forms of lung fibrosis, many
      gaps in knowledge about natural history, pathophysiology, and treatment remain.
      Investment in the research priorities enumerated above will help address these
      shortcomings and enhance patient care worldwide.

PMID- 27035783
TI  - Transbronchial Cryobiopsy Can Diagnose Constrictive Bronchiolitis in Veterans of
      Recent Conflicts in the Middle East.

PMID- 27035784
TI  - Aerosolized Antibiotics for Patients with Bronchiectasis.

PMID- 27035785
TI  - Can Warfarin Be Used in the Treatment of Pulmonary Embolism in Idiopathic
      Pulmonary Fibrosis?

PMID- 27035786
TI  - Reply: Can Warfarin Be Used in the Treatment of Pulmonary Embolism in Idiopathic
      Pulmonary Fibrosis?

PMID- 27035787
TI  - What is a Lung Nodule?

PMID- 27035788
TI  - Nitrogen-Containing Low Volatile Compounds from Pinonaldehyde-Dimethylamine
      Reaction in the Atmosphere: A Laboratory and Field Study.
AB  - Pinonaldehyde, which is among the most abundant oxidation products of alpha
      pinene, and dimethylamine were selected to study the formation of N-containing
      low volatile compounds from aldehyde-amine reactions in the atmosphere. Gas phase
      reactions took place in a Tedlar bag, which was connected to a mass spectrometer
      ionization source via a short deactivated fused silica column. In addition to on
      line analysis, abundance of gaseous precursors and reaction products were
      monitored off-line. Condensable products were extracted from the bag's walls with
      a suitable solvent and analyzed by gas chromatography coupled to chemical
      ionization high-resolution quadrupole time-of-flight mass spectrometry and by
      ultra-high-performance liquid chromatography coupled to electrospray ionization
      Orbitrap mass spectrometry. The reactions carried out resulted in several mid-low
      vapor pressure nitrogen-containing compounds that are potentially important for
      the formation of secondary organic aerosols in the atmosphere. Further, the
      presence of brown carbon, confirmed by liquid chromatography-UV-vis-mass
      spectrometry, was observed. Some of the compounds identified in the laboratory
      study were also observed in aerosol samples collected at SMEAR II station
      (Hyytiala, Finland) in August 2015 suggesting the importance of aldehyde-amine
      reactions for the aerosol formation and growth.

PMID- 27035789
TI  - MicroRNA-197 inhibits cell proliferation by targeting GAB2 in glioblastoma.
AB  - Glioblastoma is the most common type of primary brain tumor in adults, and is
      usually fatal in a short duration. Acquiring a better understanding of the
      pathogenic mechanisms of glioblastoma is essential to the design of effective
      therapeutic strategies. Grb2-associated binding protein 2 (GAB2) is a member of
      the daughter of sevenless/Gab family of scaffolding adapters, and has been
      reported to be important in the development and progression of human cancer.
      Previously, it has been reported that GAB2 is expressed at high levels in glioma,
      and may serve as a useful prognostic marker for glioma and a novel therapeutic
      target for glioma invasion intervention. Elucidating why GAB2 is overexpressed in
      glioma, and investigating how to downregulate it will assist in further
      understanding the pathogenesis and progression of the disease, and to offer novel
      targets for therapy. The present study used in situ hybridization to detect
      microRNA (miR)-197 expression levels and Targetscan to predict that the 3'-UTR of
      GAB2 was targeted by miR-197. Northern blotting and reverse transcription
      quantitative polymerase chain reaction were also conducted in the current study.
      miR-197 is downregulated in glioblastoma tissues, compared with adjacent normal
      tissues, however it involvement continues to be detected in the disease. The
      results of the present study demonstrated that miR-197, as a tumor suppressor
      gene, inhibited proliferation by regulating GAB2 in glioblastoma cells.
      Furthermore, GAB2 was not only upregulated in glioma, but its expression levels
      were also associated with the grades of glioma severity. In addition,
      overexpression of GAB2 suppressed the expression of miR-197 in glioblastoma
      cells. Therefore, restoration of miR-197 and targeting GAB2 may be used, in
      conjunction with other therapies, to prevent the progression of glioblastoma. 

PMID- 27035790
TI  - Erratum: "In Utero and Childhood Polybrominated Diphenyl Ether Exposures and Body
      Mass at Age 7 Years: The CHAMACOS Study".

PMID- 27035791
TI  - Gold-conjugated resveratrol nanoparticles attenuate the invasion and MMP-9 and
      COX-2 expression in breast cancer cells.
AB  - Gold nanoparticles (AuNPs) with antitumorigenic effects obstruct the initiation,
      development and progression of tumors via the regulation of various processes,
      such as proliferation and apoptosis. However, the effects of AuNPs on breast
      cancer metastasis have not been well studied, and their response to 12-O
      tetradecanoylphorbol-13-acetate (TPA) stimulation remains unclear. Therefore, we
      synthesized resveratrol-capped gold nanoparticles (Rev-AuNPs) using green
      nanotechnology and investigated their potential anti-invasive properties in human
      breast cancer cells in response to TPA stimulation. The Rev-AuNPs formed
      spherical nanoparticles of 22.28+/-2.98 nm in diameter. Next, we found that non
      cytotoxic concentrations of Rev-AuNPs significantly suppressed the TPA-induced
      migration and invasion abilities of breast cancer cells. Rev-AuNPs suppressed TPA
      induced enzymatic activity and the expression of matrix metalloproteinase (MMP)-9
      and cyclooxygenase-2 (COX-2). Furthermore, Rev-AuNP treatment remarkably
      downregulated TPA-induced nuclear translocation and transcriptional activation of
      nuclear transcription factor-kappaB (NF-kappaB) and activator protein-1 (AP-1).
      Rev-AuNPs reduced the phosphorylation of phosphoinositide 3-kinase/Akt (PI3K/Akt)
      and extracellular signal-regulated kinase (ERK)1/2 signaling, but did not affect
      the phosphorylation of Jun N-terminal kinase (JNK) or p38 MAPK in the TPA
      stimulated breast cancer cells. Notably, Rev-AuNPs generally showed better anti
      invasive activity than resveratrol without cytotoxicity. The inhibitory effect of
      Rev-AuNPs on MMP-9, COX-2, NF-kappaB, AP-1, PI3K/Akt and ERK activation was
      stronger than that of resveratrol for the same concentrations. We also
      demonstrated that Rev-AuNPs induced heme oxygenase-1 (HO-1) expression and that
      the inhibition of MMP-9 and COX-2 expression and MMP-9 enzymatic activity of Rev
      AuNPs were abrogated by siRNA knockdown of HO-1 expression. Our findings revealed
      that the anti-invasive effects of Rev-AuNPs in response to TPA-stimulation were
      mediated by the suppression of MMP-9, COX-2, NF-kappaB, AP-1, PI3K/Akt and ERK
      and/or the activation of HO-1 signaling cascades. This novel finding emphasizes
      the pharmacological ability of Rev-AuNPs to treat breast cancer metastasis. 

PMID- 27035792
TI  - Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol
      induces epithelial mesenchymal transition and oncogenic features.
AB  - Alcoholism is associated with breast cancer incidence and progression, and
      moderate chronic consumption of ethanol is a risk factor. The mechanisms involved
      in alcohol's oncogenic effects are unknown, but it has been speculated that they
      may be mediated by acetaldehyde. We used the immortalized normal human epithelial
      breast cell line MCF-12A to determine whether short- or long-term exposure to
      ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations,
      induces their oncogenic transformation and/or the acquisition of epithelial
      mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM
      ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0-2.5
      mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4-week incubation,
      cells were also tested for anchorage-independence, including isolation of soft
      agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were
      analyzed by immunocytofluorescence, flow cytometry, western blotting, DNA
      microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to
      ethanol, but not, in general, to acetaldehyde, was associated with
      transcriptional upregulation of the metallothionein family genes, alcohol
      metabolism genes, and genes suggesting the initiation of EMT, but without related
      phenotypic changes. Long-term exposure to the lower concentrations of ethanol or
      acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as
      demonstrated by changes in cellular phenotype, mRNA expression, and microRNA
      expression. This suggests that low concentrations of ethanol, with little or no
      mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation
      such as anchorage-independence in normal breast epithelial cells. 

PMID- 27035793
TI  - Ameliorating effect of luteolin on memory impairment in an Alzheimer's disease
      model.
AB  - Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorder.
      It is characterized by the formation of amyloid plaques and neurofibrillary
      tangles in the brain, the degeneration of cholinergic neurons and neuronal cell
      death. The present study aimed to investigate the effect of luteolin, a flavonoid
      compound, on memory impairment in a streptozotocin (STZ)-induced Alzheimer's rat
      model. Morris water maze and probe tests were performed to examine the effect of
      luteolin treatment on cognition and memory. The effect of luteolin on CA1
      pyramidal layer thickness was also examined. The results demonstrated that
      luteolin significantly ameliorated the spatial learning and memory impairment
      induced by STZ treatment. STZ significantly reduced the thickness of CA1
      pyramidal layer and treatment of luteolin completely abolished the inhibitory
      effect of STZ. Our results suggest that luteolin has a potentially protective
      effect on learning defects and hippocampal structures in AD. 

PMID- 27035795
TI  - Patience is still a virtue.

PMID- 27035794
TI  - Comment on "Effects of Atrazine on Estrogen Receptor alpha- and G Protein-Coupled
      Receptor 30-Mediated Signaling and Proliferation in Cancer Cells and Cancer
      Associated Fibroblasts".

PMID- 27035796
TI  - Water-Mediated Photochemical Treatments for Low-Temperature Passivation of Metal
      Oxide Thin-Film Transistors.
AB  - The low-temperature electrical passivation of an amorphous oxide semiconductor
      (AOS) thin-film transistor (TFT) is achieved by a deep ultraviolet (DUV) light
      irradiation-water treatment-DUV irradiation (DWD) method. The water treatment of
      the first DUV-annealed amorphous indium-gallium-zinc-oxide (a-IGZO) thin film is
      likely to induce the preferred adsorption of water molecules at the oxygen
      vacancies and leads to subsequent hydroxide formation in the bulk a-IGZO films.
      Although the water treatment initially degraded the electrical performance of the
      a-IGZO TFTs, the second DUV irradiation on the water-treated devices may enable a
      more complete metal-oxygen-metal lattice formation while maintaining low oxygen
      vacancies in the oxide films. Overall, the stable and dense metal-oxygen-metal (M
      O-M) network formation could be easily achieved at low temperatures (below 150 
      degrees C). The successful passivation of structural imperfections in the a-IGZO
      TFTs, such as hydroxyl group (OH-) and oxygen vacancies, mainly results in the
      enhanced electrical performances of the DWD-processed a-IGZO TFTs (on/off current
      ratio of 8.65 * 10(9), subthreshold slope of 0.16 V/decade, an average mobility
      of >6.94 cm(2) V(-1) s(-1), and a bias stability of DeltaVTH < 2.5 V), which show
      more than a 30% improvement over the simple DUV-treated a-IGZO TFTs.

PMID- 27035797
TI  - Over-Expression of CD200 Predicts Poor Prognosis in Cutaneous Squamous Cell
      Carcinoma.
AB  - BACKGROUND: CD200 is reported to be involved in tumor progression and can serve
      as a prognostic marker in several cancers. The purpose of this study was to
      evaluate the prognostic significance of CD200 in cutaneous squamous cell
      carcinoma (CSCC). MATERIAL/METHODS: The relative mRNA and protein expression of
      CD200 in the tumor tissues and corresponding normal tissues of 102 CSCC patients
      were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and
      Western blot analysis, respectively. The chi-square test was used to analyze the
      association between CD200 expression and clinical features of CSCC patients. In
      addition, the overall survival of the patients according to the expression level
      of CD200 was estimated by Kaplan-Meier analysis and the prognostic significance
      of the gene was analyzed by Cox regression analysis. RESULTS: Increased
      expression of CD200 was detected in the tumor tissues compared with the
      corresponding normal tissues both at mRNA and protein level. And CD200 expression
      level was associated with tumor differentiation grade (P=0.041) and clinical
      stage (P=0.004). Patients with high expression level of CD200 had a shorter
      overall survival than those with low expression (31.3 months vs. 41.9 months) and
      there was a significant difference between them (log-rank test, P<0.001). Cox
      regression analysis indicated that CD200 could be an independent marker for the
      prognosis of CSCC. CONCLUSIONS: CD200 is up-regulated and may be a novel
      biomarker for the prognosis in CSCC, and it may be a potential therapeutic target
      for CSCC.

PMID- 27035798
TI  - Substituted quinazolinones as kinase inhibitors endowed with anti-fibrotic
      properties.
AB  - Some new 3-substituted quinazolinones were synthesized and evaluated as
      inhibitors of kinases involved in fibrogenic process. The compounds were tested
      against a panel of both tyrosine and serine-threonine kinases. The profile of
      selectivity of some representative compounds was investigated through molecular
      docking studies. The most interesting compounds were also evaluated in vitro as
      potential agents for the treatment of fibrotic diseases. Quinazolinone
      derivatives reduced proliferation and expression of genes involved in the
      fibrogenic process in hepatic stellate cells (HSCs) and intestinal subepithelial
      myofibroblasts (ISEMFs). Furthermore some compounds downregulated phosphorylation
      of p38MAPK. Our findings provide evidences that 3-substituted quinazolinones
      target multiple essential pathways of the fibrogenic process. 

PMID- 27035799
TI  - Neutrophilic panniculitis and autoinflammation: what's the link?

PMID- 27035800
TI  - Stereoselective alpha-Hydroxylation of Amides Using Oppolzer's Sultam as Chiral
      Auxiliary.
AB  - An Oppolzer's sultam-based highly stereoselective alpha-hydroxylation of amides
      was developed to deliver the desired products in good yield and excellent
      diastereoselectivity (>20/1). The generally crystalline products and the
      recyclability of the chiral auxiliary illustrate the practicability and
      scalability of the current approach.

PMID- 27035801
TI  - First total synthesis of trehalose containing tetrasaccharides from Mycobacterium
      smegmatis.
AB  - Total synthesis of three important trehalose containing tetrasaccharides isolated
      from Mycobacterium smegmatis is reported for the first time, using regioselective
      opening of benzylidene acetals and stereoselective glycosylations as key steps.
      The 1,2-cis stereoselectivity in the glycosylation reactions was achieved using
      anchimeric assistance from a remote participating group, steric effects and
      solvent participation. The synthetic strategy can also be utilized for the
      assembly of structurally related oligosaccharides from M. tuberculosis. 

PMID- 27035802
TI  - Prognostic value of preoperative inflammatory response biomarkers in patients
      with sarcomatoid renal cell carcinoma and the establishment of a nomogram.
AB  - To examine the prognostic role of inflammatory response biomarkers in sarcomatoid
      renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with
      sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio
      (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte
      ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well
      established clinicopathological prognostic factors, we evaluated the prognostic
      value of this four markers using Kaplan-Meier method and Cox regression models.
      Additionally, a nomogram was established to predict the prognosis of sRCC
      patients. Elevated NLR, dNLR and PLR were significantly associated with worse
      overall survival (OS), nevertheless, elevated LMR showed an adverse effect on
      reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50
      11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a
      prognostic model including T stage, M stage, tumor necrosis and percentage of
      sarcomatoid generated a nomogram, which accurately predicted OS for sRCC
      patients. Preoperative NLR may serve as a potential prognostic biomarker in
      patients with sRCC and may help with clinical decisions about treatment
      intervention in clinical practice. The proposed nomogram can be used for the
      prediction of OS in patients with sRCC.

PMID- 27035803
TI  - Microemulsions of Record Low Amphiphile Concentrations Are Affected by the
      Ambient Gravitational Field.
AB  - It is shown that the ternary system heavy water-heptane-hexadecyl hexaethylene
      oxide (C16E6) has a stable bicontinuous microemulsion phase down to an
      exceptionally low concentration at the balanced temperature of 26.8  degrees C.
      It is further demonstrated that the ambient gravitational field has an influence
      on the observed phase equilibria for typical sample sizes (~1 cm). Direct
      measurements using a nuclear magnetic resonance imaging technique demonstrate
      that sample compositions vary with the height in the vials. It is furthermore
      found that some samples show four phases at equilibrium in apparent violation of
      Gibbs' phase rule. It is pointed out that Gibbs' phase rule strictly applies only
      when effects of gravity are negligible. A further consequence of the ambient
      gravitational field is that, for the system studied, the microemulsion one-phase
      samples are not observed, when using standard size vials, that is, sample heights
      on the order of a centimeter. Quantitative determinations of concentration
      profiles can be used to determine parameters of the free-energy density for the
      system.

PMID- 27035804
TI  - Jean-Laurent Casanova honored with the 2016 ASCI/Stanley J. Korsmeyer Award.

PMID- 27035805
TI  - Extracellular vesicles: masters of intercellular communication and potential
      clinical interventions.
AB  - Intercellular signaling via extracellular vesicles (EVs) is an underappreciated
      modality of cell-cell crosstalk that enables cells to convey packages of complex
      instructions to specific recipient cells. EVs transmit these instructions through
      their cargoes of multiple proteins, nucleic acids, and specialized lipids, which
      are derived from their cells of origin and allow for combinatorial effects upon
      recipient cells. This Review series brings together the recent progress in our
      understanding of EV signaling in physiological and pathophysiological conditions,
      highlighting how certain EVs, particularly exosomes, can promote or regulate
      infections, host immune responses, development, and various diseases - notably
      cancer. Given the diverse nature of EVs and their abilities to profoundly
      modulate host cells, this series puts particular emphasis on the clinical
      applications of EVs as therapeutics and as diagnostic biomarkers. 

PMID- 27035806
TI  - Prostasomes as a source of diagnostic biomarkers for prostate cancer.
AB  - New biomarkers are needed to improve the diagnosis of prostate cancer. Similarly
      to healthy cells, prostate epithelial cancer cells produce extracellular vesicles
      (prostasomes) that can be isolated from seminal fluid, urine, and blood.
      Prostasomes contain ubiquitously expressed and prostate-specific membrane and
      cytosolic proteins, as well as RNA. Both quantitative and qualitative changes in
      protein, mRNA, long noncoding RNA, and microRNA composition of extracellular
      vesicles isolated from prostate cancer patients have been reported. In general,
      however, the identified extracellular vesicle-associated single-marker molecules
      or combinations of marker molecules require confirmation in large cohorts of
      patients to validate their specificity and sensitivity as prostate cancer
      markers. Complications include variable factors such as prostate manipulation and
      urine flux, as well as masking by ubiquitously expressed free molecules and
      extracellular vesicles from tissues other than the prostate. Herein, we propose
      that the most promising methods include comprehensive combinational screening for
      (mutant) RNA in prostasomes that are immunoisolated with antibodies targeting
      prostate-specific epitopes. 

PMID- 27035807
TI  - Extracellular vesicle isolation and characterization: toward clinical
      application.
AB  - Two broad categories of extracellular vesicles (EVs), exosomes and shed
      microvesicles (sMVs), which differ in size distribution as well as protein and
      RNA profiles, have been described. EVs are known to play key roles in cell-cell
      communication, acting proximally as well as systemically. This Review discusses
      the nature of EV subtypes, strategies for isolating EVs from both cell-culture
      media and body fluids, and procedures for quantifying EVs. We also discuss
      proteins selectively enriched in exosomes and sMVs that have the potential for
      use as markers to discriminate between EV subtypes, as well as various
      applications of EVs in clinical diagnosis. 

PMID- 27035808
TI  - Regulation of chronic inflammatory and immune processes by extracellular
      vesicles.
AB  - Almost all cell types release extracellular vesicles (EVs), which are derived
      either from multivesicular bodies or from the plasma membrane. EVs contain a
      subset of proteins, lipids, and nucleic acids from the cell from which they are
      derived. EV factors, particularly small RNAs such as miRNAs, likely play
      important roles in cell-to-cell communication both locally and systemically. Most
      of the functions associated with EVs are in the regulation of immune responses to
      pathogens and cancer, as well as in regulating autoimmunity. This Review will
      focus on the different modes of immune regulation, both direct and indirect, by
      EVs. The therapeutic utility of EVs for the regulation of immune responses will
      also be discussed. 

PMID- 27035809
TI  - Extracellular vesicles and infectious diseases: new complexity to an old story.
AB  - Exosomes and other extracellular microvesicles (ExMVs) have important functions
      in intercellular communication and regulation. During the course of infection,
      these vesicles can convey pathogen molecules that serve as antigens or agonists
      of innate immune receptors to induce host defense and immunity, or that serve as
      regulators of host defense and mediators of immune evasion. These molecules may
      include proteins, nucleic acids, lipids, and carbohydrates. Pathogen molecules
      may be disseminated by incorporation into vesicles that are created and shed by
      host cells, or they may be incorporated into vesicles shed from microbial cells.
      Involvement of ExMVs in the induction of immunity and host defense is widespread
      among many pathogens, whereas their involvement in immune evasion mechanisms is
      prominent among pathogens that establish chronic infection and is found in some
      that cause acute infection. Because of their immunogenicity and enrichment of
      pathogen molecules, exosomes may also have potential in vaccine preparations and
      as diagnostic markers. Additionally, the ability of exosomes to deliver molecules
      to recipient cells raises the possibility of their use for drug/therapy delivery.
      Thus, ExMVs play a major role in the pathogenesis of infection and provide
      exciting potential for the development of novel diagnostic and therapeutic
      approaches. 

PMID- 27035810
TI  - Exosomes in stroke pathogenesis and therapy.
AB  - Stroke is one of the leading causes of death and disability worldwide. Stroke
      recovery is orchestrated by a set of highly interactive processes that involve
      the neurovascular unit and neural stem cells. Emerging data suggest that exosomes
      play an important role in intercellular communication by transferring exosomal
      protein and RNA cargo between source and target cells in the brain. Here, we
      review these advances and their impact on promoting coupled brain remodeling
      processes after stroke. The use of exosomes for therapeutic applications in
      stroke is also highlighted. 

PMID- 27035811
TI  - Extracellular vesicles and intercellular communication within the nervous system.
AB  - Extracellular vesicles (EVs, including exosomes) are implicated in many aspects
      of nervous system development and function, including regulation of synaptic
      communication, synaptic strength, and nerve regeneration. They mediate the
      transfer of packets of information in the form of nonsecreted proteins and
      DNA/RNA protected within a membrane compartment. EVs are essential for the
      packaging and transport of many cell-fate proteins during development as well as
      many neurotoxic misfolded proteins during pathogenesis. This form of
      communication provides another dimension of cellular crosstalk, with the ability
      to assemble a "kit" of directional instructions made up of different molecular
      entities and address it to specific recipient cells. This multidimensional form
      of communication has special significance in the nervous system. How EVs help to
      orchestrate the wiring of the brain while allowing for plasticity associated with
      learning and memory and contribute to regeneration and degeneration are all under
      investigation. Because they carry specific disease-related RNAs and proteins,
      practical applications of EVs include potential uses as biomarkers and
      therapeutics. This Review describes our current understanding of EVs and serves
      as a springboard for future advances, which may reveal new important mechanisms
      by which EVs in coordinate brain and body function and dysfunction. 

PMID- 27035812
TI  - The biology and function of exosomes in cancer.
AB  - Humans circulate quadrillions of exosomes at all times. Exosomes are a class of
      extracellular vesicles released by all cells, with a size range of 40-150 nm and
      a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes
      likely remove excess and/or unnecessary constituents from the cells, functioning
      like garbage bags, although their precise physiological role remains unknown.
      Additionally, exosomes may mediate specific cell-to-cell communication and
      activate signaling pathways in cells they fuse or interact with. Exosomes are
      detected in the tumor microenvironment, and emerging evidence suggests that they
      play a role in facilitating tumorigenesis by regulating angiogenesis, immunity,
      and metastasis. Circulating exosomes can be used as liquid biopsies and
      noninvasive biomarkers for early detection, diagnosis, and treatment of cancer
      patients. 

PMID- 27035813
TI  - Dendritic cell-derived exosomes for cancer therapy.
AB  - DC-derived exosomes (Dex) are nanometer-sized membrane vesicles that are secreted
      by the sentinel antigen-presenting cells of the immune system: DCs. Like DCs, the
      molecular composition of Dex includes surface expression of functional MHC
      peptide complexes, costimulatory molecules, and other components that interact
      with immune cells. Dex have the potential to facilitate immune cell-dependent
      tumor rejection and have distinct advantages over cell-based immunotherapies
      involving DCs. Accordingly, Dex-based phase I and II clinical trials have been
      conducted in advanced malignancies, showing the feasibility and safety of the
      approach, as well as the propensity of these nanovesicles to mediate T and NK
      cell-based immune responses in patients. This Review will evaluate the
      interactions of Dex with immune cells, their clinical progress, and the future of
      Dex immunotherapy for cancer. 

PMID- 27035814
TI  - The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic
      phenotype of thyroid cancer cells.

PMID- 27035815
TI  - Anacetrapib lowers LDL by increasing ApoB clearance in mildly
      hypercholesterolemic subjects.

PMID- 27035816
TI  - Mitochondrial metabolism mediates oxidative stress and inflammation in fatty
      liver.

PMID- 27035817
TI  - MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes.

PMID- 27035818
TI  - Genetic landscape of metastatic and recurrent head and neck squamous cell
      carcinoma.

PMID- 27035819
TI  - Immune activation caused by vascular oxidation promotes fibrosis and
      hypertension.

PMID- 27035820
TI  - Robust Brain-Machine Interface Design Using Optimal Feedback Control Modeling and
      Adaptive Point Process Filtering.
AB  - Much progress has been made in brain-machine interfaces (BMI) using decoders such
      as Kalman filters and finding their parameters with closed-loop decoder
      adaptation (CLDA). However, current decoders do not model the spikes directly,
      and hence may limit the processing time-scale of BMI control and adaptation.
      Moreover, while specialized CLDA techniques for intention estimation and assisted
      training exist, a unified and systematic CLDA framework that generalizes across
      different setups is lacking. Here we develop a novel closed-loop BMI training
      architecture that allows for processing, control, and adaptation using spike
      events, enables robust control and extends to various tasks. Moreover, we develop
      a unified control-theoretic CLDA framework within which intention estimation,
      assisted training, and adaptation are performed. The architecture incorporates an
      infinite-horizon optimal feedback-control (OFC) model of the brain's behavior in
      closed-loop BMI control, and a point process model of spikes. The OFC model
      infers the user's motor intention during CLDA-a process termed intention
      estimation. OFC is also used to design an autonomous and dynamic assisted
      training technique. The point process model allows for neural processing, control
      and decoder adaptation with every spike event and at a faster time-scale than
      current decoders; it also enables dynamic spike-event-based parameter adaptation
      unlike current CLDA methods that use batch-based adaptation on much slower
      adaptation time-scales. We conducted closed-loop experiments in a non-human
      primate over tens of days to dissociate the effects of these novel CLDA
      components. The OFC intention estimation improved BMI performance compared with
      current intention estimation techniques. OFC assisted training allowed the
      subject to consistently achieve proficient control. Spike-event-based adaptation
      resulted in faster and more consistent performance convergence compared with
      batch-based methods, and was robust to parameter initialization. Finally, the
      architecture extended control to tasks beyond those used for CLDA training. These
      results have significant implications towards the development of clinically
      viable neuroprosthetics. 

PMID- 27035821
TI  - Validation of G6PD Point-of-Care Tests among Healthy Volunteers in Yangon,
      Myanmar.
AB  - Primaquine and other 8-amnoquinoline based anti-malarials can cause haemolysis in
      subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Correct
      diagnosis of G6PD status in patients is crucial for safe treatment of both
      relapsing stages of Plasmodium vivax and transmitting forms of Plasmodium
      falciparum. Lack of suitable point-of-care tests has hampered a much needed wide
      use of primaquine for malaria elimination. In this study we have assessed the
      performances of two qualitative tests, the fluorescent spot test (FST) and the
      G6PD CareStart test (CST), against the gold standard quantitative
      spectrophotometric assay in a population of 1000 random adult healthy volunteers
      living in Yangon, Myanmar. The prevalence of G6PD deficiency in the Bamar, Karen
      and in the whole sample set was 6.6% (10.1% in males), 9.2% (21.0% in males) and
      6.8% (11.1% in males) respectively. The FST and CST showed comparable
      performances with sensitivity over 95% and specificity over 90%, however for
      cases with severe G6PD activity the FTS had improved performance. If used with a
      conservative interpretation of the signal, the CareStart test has the potential
      to be used in the field and, by allowing a wider use of primaquine, to help
      malaria elimination. 

PMID- 27035822
TI  - Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates
      Efficient Replication of Genotype-1 Hepatitis E Virus.
AB  - Hepatitis E virus (HEV) causes acute hepatitis in many parts of the world
      including Asia, Africa and Latin America. Though self-limiting in normal
      individuals, it results in ~30% mortality in infected pregnant women. It has also
      been reported to cause acute and chronic hepatitis in organ transplant patients.
      Of the seven viral genotypes, genotype-1 virus infects humans and is a major
      public health concern in South Asian countries. Sporadic cases of genotype-3 and
      4 infection in human and animals such as pigs, deer, mongeese have been reported
      primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to
      infect animals such as wild boar and camel, respectively. Genotype-3 and 4
      viruses have been successfully propagated in the laboratory in mammalian cell
      culture. However, genotype-1 virus replicates poorly in mammalian cell culture
      and no other efficient model exists to study its life cycle. Here, we report that
      endoplasmic reticulum (ER) stress promotes genotype-1 HEV replication by inducing
      cap-independent, internal initiation mediated translation of a novel viral
      protein (named ORF4). Importantly, ORF4 expression and stimulatory effect of ER
      stress inducers on viral replication is specific to genotype-1. ORF4 protein
      sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific
      antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with
      multiple viral and host proteins and assembled a protein complex consisting of
      viral helicase, RNA dependent RNA polymerase (RdRp), X, host eEF1alpha1
      (eukaryotic elongation factor 1 isoform-1) and tubulinbeta. In association with
      eEF1alpha1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma
      cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant
      genome permitted enhanced viral replication. These findings reveal a positive
      role of ER stress in promoting genotype-1 HEV replication and pave the way
      towards development of an efficient model of the virus. 

PMID- 27035823
TI  - Functional Stability of the Human Kappa Opioid Receptor Reconstituted in
      Nanodiscs Revealed by a Time-Resolved Scintillation Proximity Assay.
AB  - Long-term functional stability of isolated membrane proteins is crucial for many
      in vitro applications used to elucidate molecular mechanisms, and used for drug
      screening platforms in modern pharmaceutical industry. Compared to soluble
      proteins, the understanding at the molecular level of membrane proteins remains a
      challenge. This is partly due to the difficulty to isolate and simultaneously
      maintain their structural and functional stability, because of their hydrophobic
      nature. Here we show, how scintillation proximity assay can be used to analyze
      time-resolved high-affinity ligand binding to membrane proteins solubilized in
      various environments. The assay was used to establish conditions that preserved
      the biological function of isolated human kappa opioid receptor. In detergent
      solution the receptor lost high-affinity ligand binding to a radiolabelled ligand
      within minutes at room temperature. After reconstitution in Nanodiscs made of
      phospholipid bilayer the half-life of high-affinity ligand binding to the
      majority of receptors increased 70-fold compared to detergent solubilized
      receptors--a level of stability that is appropriate for further downstream
      applications. Time-resolved scintillation proximity assay has the potential to
      screen numerous conditions in parallel to obtain high levels of stable and active
      membrane proteins, which are intrinsically unstable in detergent solution, and
      with minimum material consumption.

PMID- 27035824
TI  - Total Lignans of Schisandra chinensis Ameliorates Abeta1-42-Induced
      Neurodegeneration with Cognitive Impairment in Mice and Primary Mouse Neuronal
      Cells.
AB  - Lignan compounds extracted from Schisandra chinensis (Turcz.) Baill. have been
      reported to possess various biological activities, and have potential in the
      treatment of Alzheimer's disease. This study was designed to investigate the
      effects of total lignans of Schisandra chinensis (TLS) on cognitive function and
      neurodegeneration in the model of AD induced by Abeta1-42 in vivo and in vitro.
      It was found that intragastric infusion with TLS (50 and 200 mg/kg) to Abeta1-42
      induced mice significantly increased the number of avoidances in the shuttle-box
      test and swimming time in the target quadrant in the Morris water maze test. TLS
      at dose of 200 mg/kg significantly restored the activities of total antioxidant
      capacity (T-AOC), as well as the level of malondialdehyde (MDA) both in the
      hippocampus and cerebral cortex in mice. Results of histopathological examination
      indicated that TLS noticeably ameliorated the neurodegeneration in the
      hippocampus in mice. On the other hand, TLS (100 MUM) could protect the Abeta1-42
      induced primary mouse neuronal cells by blocking the decrease of mitochondrial
      membrane potential (MMP), change the expressions of Bcl-2 (important regulator in
      the mitochondria apoptosis pathway). Moreover, TLS also decreased the activity of
      beta-secretase 1 (BACE1), crucial protease contributes to the hydrolysis of
      amyloid precursor protein (APP), and inhibited the expression of JKN/p38, which
      involved in the MAPKs signaling pathways in both mice and primary mouse neuronal
      cells. In summary, TLS might protect against cognitive deficits and
      neurodegeneration by releasing the damage of oxidative stress, inhibiting the
      expression of BACE1 and the MAPKs inflammatory signaling pathways. 

PMID- 27035825
TI  - GPS Tracking of Free-Ranging Pigs to Evaluate Ring Strategies for the Control of
      Cysticercosis/Taeniasis in Peru.
AB  - BACKGROUND: Taenia solium, a parasitic cestode that affects humans and pigs, is
      the leading cause of preventable epilepsy in the developing world. T. solium eggs
      are released into the environment through the stool of humans infected with an
      adult intestinal tapeworm (a condition called taeniasis), and cause cysticercosis
      when ingested by pigs or other humans. A control strategy to intervene within
      high-risk foci in endemic communities has been proposed as an alternative to mass
      antihelminthic treatment. In this ring strategy, antihelminthic treatment is
      targeted to humans and pigs residing within a 100 meter radius of a pig heavily
      infected with cysticercosis. Our aim was to describe the roaming ranges of pigs
      in this region, and to evaluate whether the 100 meter radius rings encompass
      areas where risk factors for T. solium transmission, such as open human
      defecation and dense pig activity, are concentrated. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we used Global Positioning System (GPS) devices to track
      pig roaming ranges in two rural villages of northern Peru. We selected 41 pigs
      from two villages to participate in a 48-hour tracking period. Additionally, we
      surveyed all households to record the locations of open human defecation areas.
      We found that pigs spent a median of 82.8% (IQR: 73.5, 94.4) of their time
      roaming within 100 meters of their homes. The size of home ranges varied
      significantly by pig age, and 93% of the total time spent interacting with open
      human defecation areas occurred within 100 meters of pig residences.
      CONCLUSIONS/SIGNIFICANCE: These results indicate that 100 meter radius rings
      around heavily-infected pigs adequately capture the average pig's roaming area
      (i.e., home range) and represent an area where the great majority of exposure to
      human feces occurs.

PMID- 27035826
TI  - Hydrogen Sulfide Delays LPS-Induced Preterm Birth in Mice via Anti-Inflammatory
      Pathways.
AB  - A major cause of preterm labor in pregnant women is intra-amniotic infection,
      which is mediated by an inflammatory process. Hydrogen sulfide (H2S), a gaseous
      transmitter, has been implicated to be involved in inflammatory responses. We
      sought to investigate whether H2S affects infectious preterm birth using the
      mouse model of lipopolysaccharides (LPS)-induced preterm birth. Administration of
      LPS at 0.4 mg/kg with two injections intraperitoneally (i.p.) on gestational day
      14.5 induced preterm labor. LPS significantly increased leukocyte infiltration in
      uterus, stimulated the expression of pro-inflammatory cytokines interleukin 1beta
      (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), CCL2 and CXCL15 in
      myometrium. Administration of NaHS (i.p.) delayed the onset of labor induced by
      LPS in a dose-dependent manner. NaHS prevented leukocyte infiltration into
      intrauterine tissues and inhibited the production of pro-inflammatory cytokines
      in myometrium and decreased the levels of these cytokines in maternal
      circulation. H2S also decreased LPS-activated extracellular signal-regulated
      kinase (ERK) 1/2/ nuclear factor (NF)-kappaB signaling pathways in myometrium.
      This study provides new in vivo evidence for the roles of H2S in attenuating
      inflammation, and a potential novel therapeutic strategy for infection-related
      preterm labor. 

PMID- 27035828
TI  - Impact of 20th Century Wars on the Development of Neurosurgery.
AB  - The treatment of neurosurgical casualties suffered during the wars of the 20th
      century had a significant impact on the formation and early growth of
      neurosurgery as a specialty. This chapter explores how the evolution of military
      tactics and weaponry along with the circumstances surrounding the wars themselves
      profoundly influenced the field. From the crystallization of intracranial
      projectile wound management and the formal recognition of the specialty itself
      arising from World War I experiences to the radical progress made in the outcomes
      of spinal-cord-injured soldiers in World War II or the fact that the
      neurosurgical training courses commissioned for these wars proved to be the
      precursors to modern neurosurgical training programs, the impact of the 20th
      century wars on the development of the field of neurosurgery is considerable. 

PMID- 27035827
TI  - Unstable Expression of Commonly Used Reference Genes in Rat Pancreatic Islets
      Early after Isolation Affects Results of Gene Expression Studies.
AB  - The use of RT-qPCR provides a powerful tool for gene expression studies; however,
      the proper interpretation of the obtained data is crucially dependent on accurate
      normalization based on stable reference genes. Recently, strong evidence has been
      shown indicating that the expression of many commonly used reference genes may
      vary significantly due to diverse experimental conditions. The isolation of
      pancreatic islets is a complicated procedure which creates severe mechanical and
      metabolic stress leading possibly to cellular damage and alteration of gene
      expression. Despite of this, freshly isolated islets frequently serve as a
      control in various gene expression and intervention studies. The aim of our study
      was to determine expression of 16 candidate reference genes and one gene of
      interest (F3) in isolated rat pancreatic islets during short-term cultivation in
      order to find a suitable endogenous control for gene expression studies. We
      compared the expression stability of the most commonly used reference genes and
      evaluated the reliability of relative and absolute quantification using RT-qPCR
      during 0-120 hrs after isolation. In freshly isolated islets, the expression of
      all tested genes was markedly depressed and it increased several times throughout
      the first 48 hrs of cultivation. We observed significant variability among
      samples at 0 and 24 hrs but substantial stabilization from 48 hrs onwards. During
      the first 48 hrs, relative quantification failed to reflect the real changes in
      respective mRNA concentrations while in the interval 48-120 hrs, the relative
      expression generally paralleled the results determined by absolute
      quantification. Thus, our data call into question the suitability of relative
      quantification for gene expression analysis in pancreatic islets during the first
      48 hrs of cultivation, as the results may be significantly affected by unstable
      expression of reference genes. However, this method could provide reliable
      information from 48 hrs onwards. 

PMID- 27035830
TI  - Post-Traumatic Stress Disorder among French Armed Forces Members in Afghanistan:
      A New Approach.
AB  - During the 20th century, the management of war-related psychological trauma
      shifted from neurology to psychiatry. After September 11, 2001, the French forces
      participated in a multinational force deployed in Afghanistan to fight against
      terrorism. Post-traumatic stress disorder (PTSD) became a priority. We report the
      daily work of the psychiatrists involved in this mission and the organization
      developed to psychologically support wounded military personnel. The doctrine of
      early intervention psychiatrization and the technique of collective debriefing
      are the key points of this procedure. The psychiatrist is also responsible for
      the healthcare community, particularly vulnerable when confronted with severe
      ballistic injuries. One aim of this organization is also to screen PTSD in
      soldiers returning from Afghanistan. The military general practitioner is a
      pivotal point of this procedure built to detect PTSD, anxiety, depressive
      reaction and behavioral problems. The French health service has developed a
      genuine care strategy aimed at identifying patients, accompanying them in the
      formalities for recognition and compensation, and offering them treatment locally
      by arranging clinical psychology consultations near their home. 

PMID- 27035829
TI  - Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis.
AB  - CONTEXT: Endometriosis is an estrogen-dependent, chronic inflammatory disease.
      Recent studies have shown that vitamin D (VD) is an effective modulator of the
      immune system and plays an important role in controlling many inflammatory
      diseases. OBJECTIVE: The objective of the study was to clarify the in vitro
      effects of 1,25-dihydroxy vitamin D3 (1,25[OH]2D3) on human endometriotic stromal
      cells (ESCs) and to determine the serum levels of VD in endometriosis patients.
      DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: ESCs were isolated from ovarian
      endometrioma and cultured with 1,25(OH)2D3. Gene expression of IL-8,
      cyclooxygenase-2, microsomal prostaglandin E synthase-1, microsomal prostaglandin
      E synthase-2, cytosolic prostaglandin E synthase, 15-hydroxyprostaglandin
      dehydrogenase, matrix metalloproteinase (MMP)-2, and MMP-9 was examined using
      quantitative RT-PCR. The production of IL-8 and prostaglandin E2 was measured
      using an ELISA and an enzyme immunoassay. Viable cell number was assessed using a
      cell-counting assay, and DNA synthesis was assessed using the bromodeoxyuridine
      incorporation assay. Apoptosis was assessed using flow cytometry. The expression
      of inhibitory-kappaBalpha protein was detected using Western blotting. The serum
      levels of 25-hydroxyvitamin D3 and 1,25(OH)2D3 were measured by a RIA. RESULTS:
      In vitro studies showed that 1,25(OH)2D3 significantly reduced IL-1beta- or TNF
      alpha-induced inflammatory responses, such as IL-8 expression and prostaglandin
      activity. 1,25(OH)2D3 also reduced viable ESC numbers and DNA synthesis but did
      not affect apoptosis. MMP-2 and MMP-9 expressions were reduced by 1,25(OH)2D3.
      1,25(OH)2D3 inhibited nuclear factor-kappaB activation. The serum 25
      hydroxyvitamin D3 levels were significantly lower in women with severe
      endometriosis than in the controls and women with mild endometriosis. Serum
      1,25(OH)2D3 levels were not different between groups. CONCLUSIONS: VD modulates
      inflammation and proliferation in endometriotic cells, and a lower VD status is
      associated with endometriosis. Taken together, VD supplementation could be a
      novel therapeutic strategy for managing endometriosis.

PMID- 27035831
TI  - Artificial Urinary Sphincters for Treatment of Urinary Incontinence in Elderly
      Males.
AB  - INTRODUCTION: We sought to examine the role of advanced age (defined as >70
      years), impaired cognitive function, and decreased manual dexterity in the rates
      of re-operation (revision or replacement) of artificial urinary sphincters (AUS).
      METHODS: From 1988 to 2012, 213 men underwent virgin AUS placements. Failure was
      defined as a revision performed for stress incontinence and
      replacement/exploration performed for urethral erosion/infection or mechanical
      failure. Kaplan-Meier curves were constructed to compare failure rates with age
      and Cox proportional hazard models were used to test associations. RESULTS:
      Advanced age was not associated with overall failure (p = 0.48),
      erosion/infection failure (p = 0.65), recurrent/persistent incontinence failure
      (p = 0.08), or mechanical failure (p = 0.36). Controlling for age, patients with
      cognitive dysfunction or decreased manual dexterity showed a higher rate of
      overall failure (p = 0.01). CONCLUSIONS: AUS placement is an excellent option to
      treat stress urinary incontinence in elderly men with intact cognition and good
      manual dexterity. AUS placement should be performed with caution in patients with
      impaired cognitive function or decreased manual dexterity, and additional effort
      should be made to identify these conditions both before and after surgery.

PMID- 27035832
TI  - The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila
      melanogaster.
AB  - Meiotic recombination ensures proper chromosome segregation in many sexually
      reproducing organisms. Despite this crucial function, rates of recombination are
      highly variable within and between taxa, and the genetic basis of this variation
      remains poorly understood. Here, we exploit natural variation in the inbred,
      sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to
      map genetic variants affecting recombination rate. We used a two-step crossing
      scheme and visible markers to measure rates of recombination in a 33 cM interval
      on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP
      lines. Though we cannot exclude that some biases exist due to viability effects
      associated with the visible markers used in this study, we find ~2-fold variation
      in recombination rate among lines. Interestingly, we further find that
      recombination rates are uncorrelated between the two chromosomal intervals. We
      performed a genome-wide association study to identify genetic variants associated
      with recombination rate in each of the two intervals surveyed. We refined our
      list of candidate variants and genes associated with recombination rate variation
      and selected twenty genes for functional assessment. We present strong evidence
      that five genes are likely to contribute to natural variation in recombination
      rate in D. melanogaster; these genes lie outside the canonical meiotic
      recombination pathway. We also find a weak effect of Wolbachia infection on
      recombination rate and we confirm the interchromosomal effect. Our results
      highlight the magnitude of population variation in recombination rate present in
      D. melanogaster and implicate new genetic factors mediating natural variation in
      this quantitative trait. 

PMID- 27035833
TI  - Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse
      Model of Nonalcoholic Fatty Liver Disease.
AB  - BACKGROUND: Accumulating evidence has shown that methionine- and choline
      deficient high fat (MCD+HF) diet induces the development of nonalcoholic fatty
      liver disease (NAFLD), in which elevated reactive oxygen species play a crucial
      role. We have reported that peroxiredoxin 4 (PRDX4), a unique secretory member of
      the PRDX antioxidant family, protects against NAFLD progression. However, the
      detailed mechanism and potential effects on the intestinal function still remain
      unclear. METHODS & RESULTS: Two weeks after feeding mice a MCD+HF diet, the
      livers of human PRDX4 transgenic (Tg) mice exhibited significant suppression in
      the development of NAFLD compared with wild-type (WT) mice. The serum
      thiobarbituric acid reactive substances levels were significantly lower in Tg
      mice. In contrast, the Tg small intestine with PRDX4 overexpression showed more
      suppressed shortening of total length and villi height, and more accumulation of
      lipid in the jejunum, along with lower levels of dihydroethidium binding. The
      enterocytes exhibited fewer apoptotic but more proliferating cells, and
      inflammation was reduced in the mucosa. Furthermore, the small intestine of Tg
      mice had significantly higher expression of cholesterol absorption-regulatory
      factors, including liver X receptor-alpha, but lower expression of microsomal
      triglyceride-transfer protein. CONCLUSION: Our present data provide the first
      evidence of the beneficial effects of PRDX4 on intestinal function in the
      reduction of the severity of NAFLD, by ameliorating oxidative stress-induced
      local and systemic injury. We can suggest that both liver and intestine are
      spared, to some degree, by the antioxidant properties of PRDX4.

PMID- 27035834
TI  - Neuroserpin Protects Rat Neurons and Microglia-Mediated Inflammatory Response
      Against Oxygen-Glucose Deprivation- and Reoxygenation Treatments in an In Vitro
      Study.
AB  - BACKGROUND/AIMS: Neuroserpin (NSP) is known for its neuroprotective role in
      cerebral ischemic animal models and patients. Our laboratory conducted a series
      of investigations on the neuroprotection of NSP in different cells in the brain.
      In the present study, we further observe the effects of NSP on neurons and
      microglia-mediated inflammatory response following oxygen-glucose deprivation
      (OGD), and explore possible mechanisms related to neuroprotection of OGD in the
      central nervous system (CNS). METHODS: Neurons and microglia from neonatal rats
      were treated with OGD followed by reoxygenation (OGD/R). To confirm the effects
      of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase
      (LDH) release were measured in cultured neurons. Furthermore, the levels of IL
      1beta and nitric oxide (NO) release were also detected in cultured microglia. The
      possible mechanisms for the neuroprotective effect of NSP were explored using
      Western blot analysis. RESULTS: NSP administration can reverse abnormal
      variations in neurons and microglia-mediated inflammatory response induced by
      OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH
      release were significantly improved by NSP administration in neurons.
      Simultaneously, the release of IL-1beta and NO were significantly reduced by NSP
      in microglia. Western blot showed that the expression of ERK, P38, and JNK was
      upregulated in microglia by the OGD/R treatment, and these effects were
      significantly inhibited by NSP. CONCLUSION: These data verified the
      neuroprotective effects of NSP on neurons and microglia-mediated inflammatory
      response. Inhibition of the mitogen-activated protein kinase (MAPK) signaling
      pathways might play a potential role in NSP neuroprotection on microglia-mediated
      inflammatory response, which needs further verification.

PMID- 27035835
TI  - Emergency Thoracic US: The Essentials.
AB  - Acute thoracic symptoms are common among adults visiting emergency departments in
      the United States. Adults with these symptoms constitute a large burden on the
      overall resources used in the emergency department. The wide range of possible
      causes can make a definitive diagnosis challenging, even after clinical
      evaluation and initial laboratory testing. In addition to radiography and
      computed tomography, thoracic ultrasonography (US) is an alternative imaging
      modality that can be readily performed in real time at the patient's bedside to
      help diagnose many thoracic diseases manifesting acutely and in the trauma
      setting. Advantages of US include availability, relatively low cost, and lack of
      ionizing radiation. Emergency thoracic US consists of two main parts, lung and
      pleura US and focused cardiac US, which are closely related. Acoustic mismatches
      among aerated lungs, pleura, chest wall, and pathologic conditions produce
      artifacts useful for diagnosis of pneumothorax and pulmonary edema and help in
      detection of subpleural, pleural, and chest wall pathologic conditions such as
      pneumonia, pleural effusion, and fractures. Visual assessment of cardiac
      contractility and detection of right ventricular dilatation and pericardial
      effusion at focused cardiac US are critical in patients presenting with acute
      dyspnea and trauma. Additional US examinations of the inferior vena cava for
      noninvasive volume assessment and of the groin areas for detection of deep venous
      thrombosis are often performed at the same time. This multiorgan US approach can
      provide valuable information for emergency treatment of both traumatic and
      nontraumatic thoracic diseases involving the lungs, pleura, chest wall, heart,
      and vascular system. Online supplemental material is available for this article.
      ((c))RSNA, 2016. 

PMID- 27035836
TI  - MR Imaging in Postreduction Assessment of Developmental Dysplasia of the Hip:
      Goals and Obstacles.
AB  - Developmental dysplasia of the hip is a spectrum disorder of hip development that
      ranges in severity from abnormal acetabular morphology to complete hip
      dislocation. While treatment with a Pavlik harness is highly effective in infants
      younger than 6 months, older infants and children and those with orthotic failure
      often warrant surgical reduction and placement of a spica cast, which limits
      subsequent imaging evaluation. Magnetic resonance (MR) imaging has been described
      in the evaluation of the adequacy of hip reduction for more than 2 decades, but
      the practice is still not widespread and is performed routinely at relatively few
      centers. MR imaging is a robust tool for outcome assessment after hip reduction
      and placement of a spica cast, facilitating multiplanar confirmation of
      concentric reduction independent of an ossific nucleus or orthopedic hardware.
      Excellent image contrast of soft tissues allows identification of obstacles to
      concentric reduction, which may be extra-articular or intra-articular. Extra
      articular obstacles include tightening of the adductor muscles and tightening of
      the iliopsoas tendon with constriction of the joint capsule. Intra-articular
      obstacles include limbus formation, labral inversion, an enlarged pulvinar, and
      hypertrophy of the ligamentum teres and/or the transverse acetabular ligament.
      Intravenous contrast material administration may demonstrate altered epiphyseal
      blood flow and help identify patients at risk for early ischemia. Imaging
      technique and image interpretation can be optimized to facilitate the performance
      of postreduction MR imaging studies where they may be of benefit. ((c))RSNA,
      2016.

PMID- 27035838
TI  - German Emergency Care in Neurosurgery and Military Neurology during World War II,
      1939-1945.
AB  - A critical analysis of the historical involvement of neurology and neurosurgery
      in military emergency care services enables us to better contextualize and
      appreciate the development of modern neurology at large. Wartime neurosurgery and
      civil brain science during the German Nazi period tightly coalesced in examining
      the specific injury types, which military neurosurgeons such as Wilhelm Toennis,
      Klaus Joachim Zuelch, and Georg Merrem encountered and treated based on their
      neurophysiological understanding gained from earlier peacetime research.
      Collaborative associations with Dr. Toennis in particular proved to be highly
      beneficial to other military neurologists and neurosurgeons during World War II
      and beyond. This article also discusses the prewar developments and considers the
      fate of German neurosurgeons and military neurologists after the war. The
      envisaged dynamic concepts of fast action, reaction, and recycling, which
      contemporary physicians had intensively studied in the preceding scientific
      experiments in their neurophysiological laboratories, had already been introduced
      into neurological surgery during the interwar period. In retrospect, World War II
      emergency rescue units greatly strengthened military operations through an active
      process of 'recycling' indispensable army personnel. Neurosurgical emergency
      chains thereby introduced another decisive step in the modernization of warfare,
      in that they increased the momentum of military mobility in the field.
      Notwithstanding the violence of warfare and the often inhumane ways in which such
      knowledge in the field of emergency neurology was gained, the protagonists among
      the group of experts in military neurology and neurosurgery strongly contributed
      to the postwar clinical neuroscience community in Germany. In differing political
      pretexts, this became visible in both East Germany and West Germany after the
      war, while the specific military and political conditions under which this
      knowledge of emergency medicine was obtained have largely been forgotten. 

PMID- 27035837
TI  - Expression patterns of Wnt signaling component, secreted frizzled-related protein
      3 in astrocytoma and glioblastoma.
AB  - Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble
      proteins, which modulate the Wnt signaling cascade. Novel research has identified
      aberrant expression of SFRPs in different types of cancer. In the present study
      the expression intensities and localizations of the SFRP3 protein across
      different histopathological grades of astrocytic brain tumors were investigated
      by immunohistochemistry, digital scanning and image analysis. The results
      demonstrated that the differences between expression levels and malignancy grades
      were statistically significant. Tumors were classified into four malignancy
      grades according to the World Health Organization guidelines. Moderate (P=0.014)
      and strong (P=0.028) nuclear expression levels were significantly different in
      pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher
      expression values, as compared with anaplastic astrocytoma (grade III) and
      glioblastoma (grade IV). When the sample was divided into two groups, the
      moderate and high cytoplasmic expression levels were observed to be significantly
      higher in glioblastomas than in the group comprising astrocytoma II and III.
      Furthermore, the results indicated that high grade tumors were associated with
      lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in
      comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated
      that strong cytoplasmic expression was significantly higher in the astrocytoma
      III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore,
      lower grade astrocytomas exhibited reduced membranous SFRP3 staining when
      compared with higher grade astrocytomas and this difference was statistically
      significant (P=0.036). The present results demonstrated that SFRP3 protein
      expression levels were decreased in the nucleus in higher grade astrocytoma
      (indicating the expected behavior of an antagonist of Wnt signaling), whereas
      when the SFRP3 was located in the cytoplasm an increased expression level of
      SFRP3 was identified in the high grade astrocytomas when compared with those of a
      low grade. This may suggest that SFRP3 acts as an agonist of Wnt signaling and
      promotes invasive behavior. 

PMID- 27035839
TI  - Turnover of Bacterial Cell Wall by SltB3, a Multidomain Lytic Transglycosylase of
      Pseudomonas aeruginosa.
AB  - A family of 11 lytic transglycosylases in Pseudomonas aeruginosa, an
      opportunistic human pathogen, turn over the polymeric bacterial cell wall in the
      course of its recycling, repair, and maturation. The functions of these enzymes
      are not fully understood. We disclose herein that SltB3 of P. aeruginosa is an
      exolytic lytic transglycosylase. We characterize its reaction and its products by
      the use of peptidoglycan-based molecules. The enzyme recognizes a minimum of four
      sugars in its substrate but can process a substrate comprised of a peptidoglycan
      of 20 sugars. The ultimate product of the reaction is N-acetylglucosamine-1,6
      anhydro-N-acetylmuramic acid. The X-ray structure of this enzyme is reported for
      the first time. The enzyme is comprised of four domains, arranged within an
      annular conformation. The polymeric linear peptidoglycan substrate threads
      through the opening of the annulus, as it experiences turnover.

PMID- 27035840
TI  - Letter: Safety and Efficacy Issues of Tirofiban Use in Endovascular Procedures:
      What Are the Actual Indications?

PMID- 27035841
TI  - Acute Reduction in the End-Tidal Carbon Dioxide Level During Neurosurgery:
      Another Cause for Capnography Artifact.

PMID- 27035842
TI  - Intraoperative and Postoperative Administration of Dexmedetomidine Reduces
      Anesthetic and Postoperative Analgesic Requirements in Patients Undergoing
      Cervical Spine Surgeries.
AB  - BACKGROUND: Early recovery from anesthesia and avoidance of analgesics with
      respiratory depressant properties are vital for maintenance of extubated airway
      in cervical spine surgeries. The current study investigated the role of
      dexmedetomidine as an anesthetic sparing agent and as a sole postoperative
      analgesic in these cases. MATERIALS AND METHODS: Sixty adult patients undergoing
      cervical spine surgeries were randomized into 2 groups. Group D received
      intravenous dexmedetomidine infusion 0.5 MUg/kg/h throughout the surgery after a
      loading dose of 1 MUg/kg over 10 minutes. Postoperatively, dexmedetomidine
      infusion was continued at 0.2 MUg/kg/h for 24 hours. Group C received a volume
      matched bolus and infusion of 0.9% saline. Intraoperative anesthetic requirement,
      time to recovery, and discharge were recorded. Patients were observed for rescue
      analgesic requirements for 24 hours after surgery. Hemodynamic stability,
      sedation scores, and pain scores were assessed for 48 hours after surgery.
      RESULTS: There was significant reduction in intraoperative anesthetic requirement
      in group D (P<0.001). Although sedation scores and recovery criteria were
      comparable, pain scores were significantly lower in group D compared with group C
      for first 24 hours postoperatively at all corresponding times. The mean pain-free
      period after surgery was significantly longer in group D (1460.67+/-517.16 min)
      with significantly less rescue analgesic requirement during 24-hour postoperative
      period (P=0.018) compared with group C (98.17+/-81.20 min). Hemodynamic
      parameters were maintained within clinically normal range during study period.
      CONCLUSIONS: Dexmedetomidine lowered the anesthetic requirement with clinically
      permissible hemodynamic variations without undue prolongation of recovery time.
      Postoperative dexmedetomidine infusion provided effective analgesia without
      excessive sedation in patients undergoing cervical spine surgeries.

PMID- 27035843
TI  - Editorial: Centennial Celebration - An interview with Dr Trudy Kohout on
      "Targeting Endocrine GPCRs for Better Health".

PMID- 27035846
TI  - Synthesis, physical properties and application of the zero-valent iron/titanium
      dioxide heterocomposite having high activity for the sustainable photocatalytic
      removal of hexavalent chromium in water.
AB  - A magnetic photocatalytic material composed of nanoscale zero-valent iron (nZVI)
      homogeneously distributed over a mesoporous nanocrystalline TiO2 matrix has been
      prepared by a multistage chemical process, including sol-gel technique, wet
      impregnation, and chemical reduction. X-ray powder diffraction and Raman
      spectroscopy were used for the structural and chemical characterization of the
      magnetic photocatalyst, while bulk magnetization measurements and
      scanning/transmission electron microscopy were employed to determine the physical
      and textural properties of the photocatalyst. The synthesized nZVI@TiO2
      photocatalyst shows very high efficiency in the removal of hexavalent chromium,
      Cr(vi), from water. The degradation rate follows a pseudo-first-order kinetic
      model. Most importantly, the remarkable efficiency of the photocatalyst is found
      to be due to the synergistic contributions of both counterparts, nZVI and TiO2,
      as validated by comparative experiments with neat TiO2 and nZVI@TiO2 under UV-C
      irradiation and without irradiation. New insights into the mechanism of
      synergistic degradation of chromium(vi) and suppressed oxidation of nZVI
      particles in the composite material are proposed and therein discussed.

PMID- 27035847
TI  - An exploration of Intolerance of Uncertainty and memory bias.
AB  - BACKGROUND AND OBJECTIVES: Research suggests that individuals high in Intolerance
      of Uncertainty (IU) have information processing biases, which may explain the
      close relationship between IU and worry. Specifically, high IU individuals show
      an attentional bias for uncertainty, and negatively interpret uncertain
      information. However, evidence of a memory bias for uncertainty among high IU
      individuals is limited. This study therefore explored the relationship between IU
      and memory for uncertainty. METHODS: In two separate studies, explicit and
      implicit memory for uncertain compared to other types of words was assessed.
      Cognitive avoidance and other factors that could influence information processing
      were also examined. RESULTS: IUS Factor 1 was a significant positive predictor of
      explicit memory for positive words, and IUS Factor 2 a significant negative
      predictor of implicit memory for positive words. Stimulus relevance and
      vocabulary were significant predictors of implicit memory for uncertain words.
      Cognitive avoidance was a significant predictor of both explicit and implicit
      memory for threat words. Female gender was a significant predictor of implicit
      memory for uncertain and neutral words. LIMITATIONS: Word stimuli such as those
      used in these studies may not be the optimal way of assessing information
      processing biases related to IU. In addition, the predominantly female, largely
      student sample may limit the generalizability of the findings. CONCLUSIONS:
      Future research focusing on IU factors, stimulus relevance, and both explicit and
      implicit memory, was recommended. The potential role of cognitive avoidance on
      memory, information processing, and worry was explored.

PMID- 27035848
TI  - Macrophage migration inhibitory factor promotes cardiac stem cell proliferation
      and endothelial differentiation through the activation of the PI3K/Akt/mTOR and
      AMPK pathways.
AB  - Macrophage migration inhibitory factor (MIF) has pleiotropic immune functions in
      a number of inflammatory diseases. Recent evidence from expression and functional
      studies has indicated that MIF is involved in various aspects of cardiovascular
      disease. In this study, we aimed to determine whether MIF supports in vitro c
      kit+CD45- cardiac stem cell (CSC) survival, proliferation and differentiation
      into endothelial cells, as well as the possible mechanisms involved. We observed
      MIF receptor (CD74) expression in mouse CSCs (mCSCs) using PCR and
      immunofluorescence staining, and MIF secretion by mCSCs using PCR and ELISA in
      vitro. Increasing amounts of exogenous MIF did not affect CD74 expression, but
      promoted mCSC survival, proliferation and endothelial differentiation. By
      contrast, treatment with an MIF inhibitor (ISO-1) or siRNA targeting CD74 (CD74
      siRNA) suppressed the biological changes induced by MIF in the mCSCs. Increasing
      amounts of MIF increased the phosphorylation of Akt and mammalian target of
      rapamycin (mTOR), which are known to support cell survival, proliferation and
      differentiation. These effects of MIF on the mCSCs were abolished by LY294002 [a
      phosphoinositide 3-kinase (PI3K) inhibitor] and MK-2206 (an Akt inhibitor).
      Moreover, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation
      increased following treatment with MIF. The AMPK inhibitor, compound C, partly
      blocked the pro-proliferative effects of MIF on the mCSCs. In conclusion, our
      results suggest that MIF promotes mCSC survival, proliferation and endothelial
      differentiation through the activation of the PI3K/Akt/mTOR and AMPK signaling
      pathways. Thus, MIF may prove to be a potential therapeutic factor in the
      treatment of heart failure and myocardial infarction by activating CSCs.

PMID- 27035850
TI  - Translocation of Functionalized Multi-Walled Carbon Nanotubes across Human
      Pulmonary Alveolar Epithelium: Dominant Role of Epithelial Type 1 Cells.
AB  - Uptake and translocation of short functionalized multi-walled carbon nanotubes
      (short-fMWCNTs) through the pulmonary respiratory epithelial barrier depend on
      physicochemical property and cell type. Two monoculture models, immortalized
      human alveolar epithelial type 1 (TT1) cells and primary human alveolar
      epithelial type 2 cells (AT2), which constitute the alveolar epithelial barrier,
      were employed to investigate the uptake and transport of 300 and 700 nm in
      length, poly(4-vinylpyridine)-functionalized, multi-walled carbon nanotubes
      (p(4VP)-MWCNTs) using quantitative imaging and spectroscopy techniques. The
      p(4VP)-MWCNT exhibited no toxicity on TT1 and AT2 cells, but significantly
      decreased barrier integrity (*p < 0.01). Uptake of p(4VP)-MWCNTs was observed in
      70% of TT1 cells, correlating with compromised barrier integrity and basolateral
      p(4VP)-MWCNT translocation. There was a small but significantly greater uptake of
      300 nm p(4VP)-MWCNTs than 700 nm p(4VP)-MWCNTs by TT1 cells. Up to 3% of both the
      300 and 700 nm p(4VP)-MWCNTs reach the basal chamber; this relatively low amount
      arose because the supporting transwell membrane minimized the amount of p(4VP)
      MWCNT translocating to the basal chamber, seen trapped between the basolateral
      cell membrane and the membrane. Only 8% of AT2 cells internalized p(4VP)-MWCNT,
      accounting for 17% of applied p(4VP)-MWCNT), with transient effects on barrier
      function, which initially fell then returned to normal; there was no MWCNT
      basolateral translocation. The transport rate was MWCNT length modulated. The
      comparatively lower p(4VP)-MWCNT uptake by AT2 cells is proposed to reflect a
      primary barrier effect of type 2 cell secretions and the functional differences
      between the type 1 and type 2 alveolar epithelial cells.

PMID- 27035849
TI  - Expression of SOFAT by T- and B-lineage cells may contribute to bone loss.
AB  - A novel T cell-secreted cytokine, termed secreted osteoclastogenic factor of
      activated T cells (SOFAT) that induces osteoclastic bone resorption in a RANKL
      independent manner, has been described. Our group have previously reported that
      SOFAT is highly expressed in gingival tissues of patients with chronic
      periodontitis suggesting a putative role in the bone loss associated with
      periodontal disease. The aim of the present study was to identify other potential
      cellular sources of SOFAT in the bone resorptive lesions of patients with
      periodontal disease. Gingival tissues were biopsied from systemically healthy
      subjects without periodontal disease (n=5) and patients with chronic
      periodontitis (n=5), and the presence of SOFAT was analyzed by
      immunohistochemistry and immunofluorescence staining. The present data
      demonstrated marked SOFAT staining in diseased periodontal tissues that was
      predominantly associated with the lymphocytic infiltration of gingival tissues.
      Notably, in addition to CD3+ T cells, B-lineage cells including plasma cells also
      exhibited strong staining for SOFAT. As SOFAT has not previously been reported in
      B-lineage cells, splenic T cells and B cells were further purified from BALB/c
      mice and activated using CD3/CD28 and lipopolysaccharide, respectively. SOFAT was
      quantified by reverse transcription-quantitative polymerase chain reaction and
      was shown to be significantly expressed (P<0.05) in both activated T cells and B
      cells compared with unstimulated cells. These data support a putative role of
      SOFAT in the bone loss associated with chronic periodontal disease. In addition,
      to the best of our knowledge, this study demonstrates for the first time that in
      addition to T cells, B-lineage cells may also be a significant source of SOFAT in
      inflammatory states. 

PMID- 27035851
TI  - Inhibitory role of TRIP-Br1 oncoprotein in hypoxia-induced apoptosis in breast
      cancer cell lines.
AB  - TRIP-Br1 oncoprotein is known to be involved in many vital cellular functions. In
      this study, we examined the role of TRIP-Br1 in hypoxia-induced cell death.
      Exposure to the overcrowded and CoCl2-induced hypoxic conditions increased TRIP
      Br1 expression at the protein level in six breast cancer cell lines (MCF7, MDA-MB
      231, T47D, Hs578D, BT549, and MDA-MB-435) but resulted in no significant change
      in three normal cell lines (MCF10A, MEF and NIH3T3). Our result revealed that
      CoCl2-induced hypoxia stimulated apoptosis and autophagy, in which TRIP-Br1
      expression was found to be upregulated. Interestingly, TRIP-Br1 silencing in the
      MCF7 and MDA-MB-231 cancer cells accelerated apoptosis and destabilization of
      XIAP under the CoCl2-induced hypoxic condition, implying that TRIP-Br1 may render
      cancer cells resistant to apoptosis through the stabilization of XIAP. We also
      propose that TRIP-Br1 seems to be upregulated at least partly as a result of the
      inhibition of PI3K/AKT signaling pathway and the overexpression of HIF-1alpha. In
      conclusion, our findings suggest that TRIP-Br1 functions as an oncogenic protein
      by providing cancer cells resistance to the hypoxia-induced cell death. 

PMID- 27035852
TI  - Impact of migration on tuberculosis epidemiology and control in the EU/EEA.

PMID- 27035853
TI  - Liposome Bupivacaine Femoral Nerve Block for Postsurgical Analgesia after Total
      Knee Arthroplasty.
AB  - BACKGROUND: The authors evaluated the efficacy of liposome bupivacaine in a
      femoral nerve block (FNB) after total knee arthroplasty. METHODS: Part 1:
      subjects received FNB with 20 ml liposome bupivacaine (67, 133, or 266 mg) or
      placebo. Part 2: subjects were randomized to FNB with liposome bupivacaine 266 mg
      or placebo. The primary outcome measure was area under the curve of the numeric
      rating scale score for pain intensity at rest through 72 h (AUC NRS-R0-72) with
      imputed scores after rescue medication. RESULTS: In part 1, FNB with liposome
      bupivacaine 266 mg (n = 24) resulted in analgesia similar to that obtained with
      133 mg and was chosen for part 2. In part 2, least-squares mean (standard error)
      AUC NRS-R0-72 was lower with liposome bupivacaine 266 mg (n = 92) than with
      placebo (n = 91; 419 [17] vs. 516 [17]; P < 0.0001). This outcome remained
      unchanged in a post hoc analysis without score imputation (221 [12] vs. 282 [12];
      P = 0.0005). Least-squares mean AUC NRS-R with imputed scores was lower with
      liposome bupivacaine during each 24-h interval (0 to 24, 24 to 48, and 48 to 72
      h) after surgery; AUC NRS-R without imputed scores was lower during the 0- to 24
      h and 24- to 48-h intervals. The liposome bupivacaine group had lower mean total
      opioid use (76 vs. 103 mg morphine; P = 0.0016). Pain was sufficiently severe to
      require second-step rescue with opioids via intravenously administered patient
      controlled analgesia in 92% of liposome bupivacaine patients and 81% of placebo
      patients. With patient-controlled analgesia and other forms of rescue analgesia,
      mean NRS scores with activity were moderate in both liposome bupivacaine and
      placebo groups throughout the part 2 study period. Incidence of adverse events
      was similar between the groups (part 1: 90 vs. 96%; part 2: 96 vs. 96%,
      respectively). CONCLUSION: FNB with liposome bupivacaine (266 mg) resulted in
      modestly lower pain scores and reduced opioid requirements after surgery, with an
      adverse event profile similar to placebo.

PMID- 27035854
TI  - Differential Perceptions of Noninvasive Ventilation in Intensive Care among
      Medical Caregivers, Patients, and Their Relatives: A Multicenter Prospective
      Study-The PARVENIR Study.
AB  - BACKGROUND: Noninvasive ventilation (NIV) requires a close "partnership" between
      a conscious patient and the patient's caregivers. Specific perceptions of NIV
      stakeholders and their impact have been poorly described to date. The objectives
      of this study were to compare the perceptions of NIV by intensive care unit (ICU)
      physicians, nurses, patients, and their relatives and to explore factors
      associated with caregivers' willingness to administer NIV and patients' and
      relatives' anxiety in relation to NIV. METHODS: This is a prospective,
      multicenter questionnaire-based study. RESULTS: Three hundred and eleven ICU
      physicians, 752 nurses, 396 patients, and 145 relatives from 32 ICUs answered the
      questionnaire. Nurses generally reported more negative feelings and more frequent
      regrets about providing NIV (median score, 3; interquartile range, [1 to 5] vs. 1
      [1 to 5]; P < 0.0001) compared to ICU physicians. Sixty-four percent of ICU
      physicians and only 32% of nurses reported a high level of willingness to
      administer NIV, which was independently associated with NIV case-volume and
      workload. A high NIV session-related level of anxiety was observed in 37% of
      patients and 45% of relatives. "Dyspnea during NIV," "long NIV session," and "the
      need to have someone at the bedside" were identified as independent risk factors
      of high anxiety in patients. CONCLUSIONS: Lack of willingness of caregivers to
      administer NIV and a high level of anxiety of patients and relatives in relation
      to NIV are frequent in the ICU. Most factors associated with low willingness to
      administer NIV by nurses or anxiety in patients and relatives may be amenable to
      change. Interventional studies are now warranted to evaluate how to reduce these
      risk factors and therefore contribute to better management of a potentially
      traumatic experience. (Anesthesiology 2016; 124:1347-59).

PMID- 27035856
TI  - Tarlov Cysts: Incidental Finding during Subarachnoid Drain Placement.

PMID- 27035858
TI  - Inhibition of autophagic flux by ROS promotes apoptosis during DTT-induced
      ER/oxidative stress in HeLa cells.
AB  - As targets for cancer therapy, endoplasmic reticulum (ER) stress and autophagy
      are closely linked. However, the signaling pathways responsible for induction of
      autophagy in response to ER stress and its cellular consequences appear to vary
      with cell type and stimulus. In the present study, we showed that dithiothreitol
      (DTT) induced ER stress in HeLa cells in a time- and dose-dependent fashion. With
      increased ER stress, reactive oxygen species (ROS) production increased and
      autophagy flux, assessed by intracellular accumulation of LC3B-II and p62, was
      inhibited. N-acetyl-L-cysteine (NAC), a classic antioxidant, exacerbated cell
      death induced by 3.2 mM of DTT, but attenuated that induced by 6.4 mM DTT. Low
      cytotoxic doses of DTT transiently activated c-JNU N-terminal kinase (JNK) and
      p38, whereas high dose of DTT persistently activated JNK and p38 and
      simultaneously reduced extracellular signal-regulated kinase (ERK) activity.
      Combined treatment with DTT and U0126, an inhibitor of ERK upstream activators
      mitogen-activated protein kinase (MAPK) kinase 1 and 2 (MEK1/2), blocked
      autophagy flux in HeLa cells. This effect was similar to that caused by a
      combination of DTT and chloroquine (CQ). These data suggested that insufficient
      autophagy was accompanied by increased ROS production during DTT-induced ER
      stress. ROS appeared to regulate MAPK signaling, switching from a pro-survival to
      a pro-apoptotic signal as ER stress increased. ERK inhibition by ROS during
      severe ER stress blocked autophagic flux. Impaired autophagic flux, in turn,
      aggravated ER stress, ultimately leading to cell death. Taken together, our data
      provide the first reported evidence that ROS may control cell fate through
      regulating the MAPK pathways and autophagic flux during DTT-induced ER/oxidative
      stress. 

PMID- 27035857
TI  - Well Baby Group Care: Evaluation of a Promising Intervention for Primary Obesity
      Prevention in Toddlers.
AB  - BACKGROUND: Nationally, approximately 24% of preschool children are overweight or
      obese, with low-income communities disproportionately affected. Few interventions
      to prevent obesity in children at greatest risk have demonstrated positive
      results. Therefore, we evaluated the effectiveness of a novel group well-child
      care intervention for primary obesity prevention at age 2 years. METHODS: Well
      Baby Group (WBG) is an alternative to traditional well-child care offered at a
      federally qualified health center in the South Bronx. Facilitated by a
      pediatrician and nutritionist, WBG fosters positive dietary behaviors, responsive
      parenting and feeding practices, and peer support during the first 18 months of
      life. Multivariable logistic regression was conducted to test the effect of WBG
      on rates of overweight/obesity at 2 years (BMI-for-age >=85th percentile) using a
      nonrandomized comparison group of children receiving traditional care at our
      center over the same period. RESULTS: Characteristics of mothers and infants were
      comparable between intervention (n = 47) and comparison (n = 140) groups.
      Children enrolled in WBG were significantly less likely to be overweight/obese at
      2 years than children receiving traditional well-child care (2.1% vs. 15.0%; OR
      0.12; 95% CI 0.02-0.94; p = 0.02). In multivariable regression analysis, WBG
      remained a significant independent protective factor (OR 0.12; 95% CI 0.02-0.93;
      p = 0.04), adjusting for birthweight and parity. CONCLUSIONS: WBG, a replicable
      model integrated into primary care visits, affords a unique opportunity to
      intervene consistently and early, providing families in at-risk communities with
      increased provider time, intensive education, and ongoing support. Further study
      of group well-child care for primary obesity prevention is warranted to confirm
      the effectiveness of the model.

PMID- 27035859
TI  - Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer
      drugs through suppression of the nuclear factor kappaB pathway.
AB  - Multiple myeloma (MM) is still an incurable hematological malignancy with a 5
      year survival rate of ~35%, despite the use of various treatment options. The
      nuclear factor kappaB (NF-kappaB) pathway plays a crucial role in the
      pathogenesis of MM. Thus, inhibition of the NF-kappaB pathway is a potential
      target for the treatment of MM. In a previous study, we showed that mangiferin
      suppressed the nuclear translocation of NF-kappaB. However, the treatment of MM
      involves a combination of two or three drugs. In this study, we examined the
      effect of the combination of mangiferin and conventional anticancer drugs in an
      MM cell line. We showed that the combination of mangiferin and an anticancer drug
      decreased the viability of MM cell lines in comparison with each drug used
      separately. The decrease in the combination of mangiferin and an anticancer drug
      induced cell viability was attributed to increase the expression of p53 and Noxa
      and decreases the expression of XIAP, survivin, and Bcl-xL proteins via
      inhibition of NF-kappaB pathway. In addition, the combination treatment caused
      the induction of apoptosis, activation of caspase-3 and the accumulation of the
      cells in the sub-G1 phase of the cell cycle. Our findings suggest that the
      combination of mangiferin and an anticancer drug could be used as a new regime
      for the treatment of MM. 

PMID- 27035860
TI  - Forced transport of self-propelled particles in a two-dimensional separate
      channel.
AB  - Transport of self-propelled particles in a two-dimensional (2D) separate channel
      is investigated in the presence of the combined forces. By applying an ac force,
      the particles will be trapped by the separate walls. A dc force produces the
      asymmetry of the system and induces the longitudinal directed transport. Due to
      the competition between self-propulsion and the combined external forces, the
      transport is sensitive to the self-propelled speed and the particle radius, thus
      one can separate the particles based on these properties. 

PMID- 27035861
TI  - A Gaussian Wave Packet Propagation Approach to Vibrationally Resolved Optical
      Spectra at Non-Zero Temperatures.
AB  - An effective time dependent approach based on a method that is similar to the
      Gaussian wave packet propagation (GWP) technique of Heller is developed for the
      computation of vibrationally resolved electronic spectra at finite temperatures
      in the harmonic, Franck-Condon/Hertzberg-Teller approximations. Since the
      vibrational thermal density matrix of the ground electronic surface and the time
      evolution operator on that surface commute, it is possible to write the spectrum
      generating correlation function as a trace of the time evolved doorway state. In
      the stated approximations, the doorway state is a superposition of the harmonic
      oscillator zero and one quantum eigenfunctions and thus can be propagated by the
      GWP. The algorithm has an O(N(3)) dependence on the number of vibrational modes.
      An application to pyrene absorption spectrum at two temperatures is presented as
      a proof of the concept.

PMID- 27035862
TI  - Automatic segmentation of maxillofacial cysts in cone beam CT images.
AB  - Accurate segmentation of cysts and tumors is an essential step for diagnosis,
      monitoring and planning therapeutic intervention. This task is usually done
      manually, however manual identification and segmentation is tedious. In this
      paper, an automatic method based on asymmetry analysis is proposed which is
      general enough to segment various types of jaw cysts. The key observation
      underlying this approach is that normal head and face structure is roughly
      symmetric with respect to midsagittal plane: the left part and the right part can
      be divided equally by an axis of symmetry. Cysts and tumors typically disturb
      this symmetry. The proposed approach consists of three main steps as follows: At
      first, diffusion filtering is used for preprocessing and symmetric axis is
      detected. Then, each image is divided into two parts. In the second stage, free
      form deformation (FFD) is used to correct slight displacement of corresponding
      pixels of the left part and a reflected copy of the right part. In the final
      stage, intensity differences are analyzed and a number of constraints are
      enforced to remove false positive regions. The proposed method has been validated
      on 97 Cone Beam Computed Tomography (CBCT) sets containing various jaw cysts
      which were collected from various image acquisition centers. Validation is
      performed using three similarity indicators (Jaccard index, Dice's coefficient
      and Hausdorff distance). The mean Dice's coefficient of 0.83, 0.87 and 0.80 is
      achieved for Radicular, Dentigerous and KCOT classes, respectively. For most of
      the experiments done, we achieved high true positive (TP). This means that a
      large number of cyst pixels are correctly classified. Quantitative results of
      automatic segmentation show that the proposed method is more effective than one
      of the recent methods in the literature.

PMID- 27035863
TI  - Post-processing techniques for making reliable measurements from curve-skeletons.
AB  - Interconnected 3-D networks occur widely in biology and the geometry of such
      branched networks can be described by curve-skeletons, allowing parameters such
      as path lengths, path tortuosities and cross-sectional thicknesses to be
      quantified. However, curve-skeletons are typically sensitive to small scale
      surface features which may arise from noise in the imaging data. In this paper,
      new post-processing techniques for curve-skeletons are presented which ensure
      that measurements of lengths and thicknesses are less sensitive to these small
      scale surface features. The techniques achieve sub-voxel accuracy and are based
      on a minimal sphere-network representation in which the object is modelled as a
      string of minimally overlapping spheres, and as such samples the object on a
      scale related to the local thickness. A new measure of cross-sectional dimension
      termed the modal radius is defined and shown to be more robust in comparison with
      the standard measure (the internal radius), while retaining the desirable feature
      of capturing the size of structures in terms of a single measure. The techniques
      are demonstrated by application to trabecular bone and tumour vascular network
      case studies where the volumetric data was obtained by high resolution computed
      tomography.

PMID- 27035864
TI  - Rapid dynamic changes of the geometry of the anterior segment of the eye: A
      method of automatic spatial correction of a temporal sequence of OCT images.
AB  - INTRODUCTION: Ocular dynamics is a very complex phenomenon which has not been
      well studied and understood yet. The way in which the eye responds to pulsatile
      changes of the blood pressure or even the electric activity of the heart depends
      not only on the mechanical properties of each individual structure of the eye
      globe, but also on its internal conditions, such as the degree of accommodation
      or intraocular pressure (IOP). METHOD: This paper presents a method for
      correcting these undesired movements that could increase the sensitivity of the
      technique and its reliability in the estimation of pulsatile dynamics. The
      presented algorithm uses fully automatic detection of the structures that form an
      angle and fully automatic stabilisation of each individual image being a part of
      a captured sequence. RESULTS AND CONCLUSIONS: The procedures described above were
      applied to the data of nine subjects taking part in the study. For all of them it
      turned out that the most representative area for fitting the images is the area
      of the irido-corneal angle apex. The presented algorithm significantly improved
      the spatial stability of the images in the temporal sequences of the tomographic
      images. The use of such correction makes it possible to distinguish the subtle
      pulsatile fluctuations of the ocular structures in the anterior segment, that can
      be associated with the activity of the retinal blood vessels and/or electric
      activity of the heart, from the undesired involuntary movements of the eye or the
      whole head.

PMID- 27035865
TI  - Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic
      cancer cells via suppression of the hedgehog signaling pathway.
AB  - Hypoxic microenvironment, a common feature of pancreatic cancer, is associated
      with tumor proliferation, metastasis and epithelial-mesenchymal transition (EMT)
      changes. In recent years, many natural agents, including curcumin, have been
      proven to possess the ability to inhibit the progression of pancreatic cancer.
      However, whether curcumin is able to suppress hypoxia-induced pancreatic cancer
      progression and the underlying mechanisms are still not fully elucidated. The aim
      of the present study was to evaluate whether curcumin affects hypoxia-induced EMT
      and the activation of Hh signaling pathway in pancreatic cancer. The human
      pancreatic cancer cell line Panc-1, was treated with hypoxic condition and
      curcumin. Cell proliferation was assessed by the MTT assay. Wound healing assay
      and transwell invasion assay were used to detect the migratory and invasive
      activity of cancer cells. The EMT-related factors, E-cadherin, N-cadherin,
      vimentin were detected by QT-PCR, western blot analysis and immunofluorescence
      staining. The Hh signaling-related factors, SHH, SMO and GLI1 were detected by
      western blot analysis. The results of present study showed that curcumin could
      not only inhibit the hypoxia-induced cell proliferation, migration and invasion
      in pancreatic cancer, but also mediate the expression of EMT-related factors. In
      addition, curcumin remarkably inhibited hypoxia-mediated activation of Hh
      signaling pathway. Taken together, these data indicate that curcumin plays an
      important role in suppressing hypoxia-induced pancreatic cancer metastasis by
      inhibiting the Hh signaling pathway. Curcumin might be a potential candidate for
      chemoprevention of this severe disease. 

PMID- 27035866
TI  - Phenomenological thermodynamics and the structure formation mechanism of the
      CuTi2S4 rhombohedral phase.
AB  - The theory of structural phase transition in CuTi2S4 is proposed. The symmetry of
      order parameters, thermodynamics and the mechanism of the atomic structure
      formation of the rhombohedral Cu-Ti-thiospinel have been studied. The critical
      order parameter inducing the phase transition has been found. Within the Landau
      theory of phase transitions, it is shown that the phase state may change from the
      high-symmetry cubic disordered Fd3[combining macron]m phase to the low-symmetry
      ordered rhombohedral R3[combining macron]m phase as a result of phase transition
      of the first order close to the second order. It is shown that the rhombohedral
      structure of CuTi2S4 is formed as a result of the displacements of all types of
      atoms and the ordering of Cu-atoms (1 : 1 order type in tetrahedral spinel
      sites), Ti-atoms (1 : 1 : 6 order type in octahedral spinel sites), and S-atoms
      (1 : 1 : 3 : 3 order type). The Cu- and Ti-atoms form metal nanoclusters which
      are named a "bunch" of dimers. The "bunch" of dimers in CuTi2S4 is a new type of
      self-organization of atoms in frustrated spinel-like structures. It is shown that
      Ti-atoms also form other types of metal nanoclusters: trimers and tetrahedra.

PMID- 27035867
TI  - Characteristics of B cell-associated gene expression in patients with coronary
      artery disease.
AB  - The current study aimed to identify differentially expressed B cell-associated
      genes in peripheral blood mononuclear cells and observe the changes in B cell
      activation at different stages of coronary artery disease. Groups of patients
      with acute myocardial infarction (AMI) and stable angina (SA), as well as healthy
      volunteers, were recruited into the study (n=20 per group). Whole human genome
      microarray analysis was performed to examine the expression of B cell-associated
      genes among these three groups. The mRNA expression levels of 60 genes associated
      with B cell activity and regulation were measured using reverse transcription
      quantitative polymerase chain reaction. The mRNA expression of the B cell antigen
      receptor (BCR)-associated genes, CD45, NFAM, SYK and LYN, were significantly
      upregulated in patients with AMI; however, FCRL3, CD79B, CD19, CD81, FYN, BLK,
      CD22 and CD5 mRNA expression levels were significantly downregulated, compared
      with patients in the SA and control group. The mRNA levels of the T-independent B
      cell-associated genes, CD16, CD32, LILRA1 and TLR9, were significantly increased
      in AMI patients compared with SA and control patients. The mRNA expression of
      genes associated with T-dependent B cells were also measured: EMR2 and CD97 were
      statistically upregulated, whereas SLAMF1, LY9, CD28, CD43, CD72, ICOSL, PD1,
      CD40 and CD20 mRNAs were significantly downregulated in AMI group patients
      compared with the two other groups. Additionally the gene expression levels of B
      cell regulatory genes were measured. In patients with AMI, CR1, LILRB2, LILRB3
      and VAV1 mRNA expression levels were statistically increased, whereas, CS1 and
      IL4I1 mRNAs were significantly reduced compared with the SA and control groups.
      There was no statistically significant difference in B cell-associated gene
      expression levels between patients with SA and the control group. The present
      study identified the downregulation of genes associated with BCRs, B2 cells and B
      cell regulators in patients with AMI, indicating a weakened T cell-B cell
      interaction and reduced B2 cell activation during AMI. Thus, improving B2 cell
      mediated humoral immunity may be a potential target for medical intervention in
      patients with AMI. 

PMID- 27035868
TI  - The cyclic AMP signaling pathway: Exploring targets for successful drug discovery
      (Review).
AB  - During development of disease, complex intracellular signaling pathways regulate
      an intricate series of events, including resistance to external toxins, the
      secretion of cytokines and the production of pathological phenomena. Adenosine
      3',5'-cyclic monophosphate (cAMP) is a nucleotide that acts as a key second
      messenger in numerous signal transduction pathways. cAMP regulates various
      cellular functions, including cell growth and differentiation, gene transcription
      and protein expression. This review aimed to provide an understanding of the
      effects of the cAMP signaling pathway and the associated factors on disease
      occurrence and development by examining the information from a new perspective.
      These novel insights aimed to promote the development of novel therapeutic
      approaches and aid in the development of new drugs. 

PMID- 27035869
TI  - The decreased expression of electron transfer flavoprotein beta is associated
      with tubular cell apoptosis in diabetic nephropathy.
AB  - Tubular injury is closely correlated with the development of progressive diabetic
      nephropathy (DN), particularly in cases of type 2 diabetes. The apoptosis of
      tubular cells has been recognized as a major cause of tubular atrophy, followed
      by tubulointerstitial fibrosis. Electron transfer flavoprotein beta (ETFbeta) is
      known as an important electron acceptor in energy metabolism, but its role in DN
      was not fully understood. In the present study, we examined the expression
      pattern of ETFbeta using diabetic kidney samples and further investigated ETFbeta
      involvement in tubular epithelial cell (TEC) apoptosis. Human renal biopsy
      specimens from patients with DN as well as a spontaneous rat model of diabetes
      using Otsuka Long-Evans Tokushima fatty (OLETF) rats, were employed in order to
      examine the expression of ETFbeta and cell apoptosis in kidneys during the
      development of DN (for the rats, at 36 and 56 weeks of age respectively).
      Moreover, ETFbeta siRNA was used to investigate the role of ETFbeta in the
      apoptosis of renal tubular cells. Our present results showed that the expression
      of ETFbeta in the kidneys was progressively decreased both in patients with DN
      and OLETF rats, which coincided with progressive renal injury and TEC apoptosis.
      In addition, the in vitro study demonstrated that knockdown of ETFbeta caused
      apoptosis in tubular cells, as proven by the increased expression of pro
      apoptotic proteins and TUNEL assay. Therefore, the findings of our present study
      suggest that ETFbeta plays an important role in renal tubular cell apoptosis
      during the progression of DN.

PMID- 27035870
TI  - Knockdown of LI-cadherin alters expression of matrix metalloproteinase-2 and -9
      and galectin-3.
AB  - Liver-intestine cadherin (LI-cadherin), a novel member of the cadherin family,
      has been associated with the ability of a tumor to acquire an aggressive
      phenotype in several types of cancer. However, the exact function of LI-cadherin
      in the process of tumor invasion and metastasis remains predominantly unknown. To
      explore the effect of LI-cadherin on the regulation of matrix metalloproteinase-2
      (MMP-2), MMP-9 and galectin-3 in LoVo human colorectal cancer cells, a RNA
      interference technique was applied to suppress the expression of LI-cadherin.
      Subsequently, the mRNA levels and activities of MMP-2 and -9 were analyzed by
      semi-quantitative reverse transcription-polymerase chain reaction and gelatin
      zymography, respectively. Additionally, the protein expression level of galectin
      3 was determined by western blot analysis. The results of the present study
      demonstrated that short hairpin RNA (shRNA)-silencing of LI-cadherin
      significantly increased the mRNA levels and activities of MMP-2 and -9, and
      significantly reduced the protein levels of galectin-3 in LoVo cells compared
      with control shRNA (P<0.05). These data indicate that knockdown of LI-cadherin
      facilitates the invasion of cancer cells by degrading extracellular matrix
      components via activation of MMP-2 and -9, and increases cancer cell adhesion and
      migration via altered expression of galectin-3. This suggests that LI-cadherin
      serves an important role in the invasion and metastasis of colorectal cancer, and
      may be used as a potential therapeutic target. 

PMID- 27035871
TI  - Clozapine and risperidone in moderately refractory schizophrenia: a 6-month
      randomized double-blind comparison.
AB  - OBJECTIVE: Clozapine remains the only medication indicated for refractory
      schizophrenia. As new antipsychotic drugs become available, their efficacy
      compared to clozapine, particularly in moderately ill patients, is of great
      clinical interest. We compared risperidone, the first of these, to clozapine in
      partially responsive patients. Further, since participation of patients usually
      excluded from clinical trials is increasingly important, we broadened inclusion
      to a wider patient population. METHODS: We compared clozapine (n = 53) to
      risperidone (n = 54) in a randomized, double-blind, 29-week trial in
      schizophrenia patients (diagnosed using DSM-IV) at 3 research outpatient clinics.
      Randomization was stratified by "narrow" or "broad" inclusion criteria. The study
      was conducted between December 1995 and October 1999. Time to treatment
      discontinuation for lack of efficacy and time to 20% improvement in the Brief
      Psychiatric Rating Scale psychotic symptom cluster were the primary outcome
      measures. RESULTS: There were no differences in all-cause discontinuation;
      clozapine-treated participants were significantly less likely to discontinue for
      lack of efficacy (15%) than risperidone-treated participants (38%) (Wilcoxon
      chi(2)1 = 6.10, P = .01). Clozapine resulted in significantly more global
      improvement (F2,839 = 6.07, P < .01) and asociality improvement (F2,315 = 6.64, P
      < .01) than risperidone. There was no difference in proportions meeting an a
      priori criterion of psychosis improvement (risperidone: 57%; clozapine: 71%).
      Significant adverse effect differences in salivation (F1 = 4.05, P < .05) (F1 =
      12.13, P < .001), sweating (F1 = 5.07, P < .05), and tachycardia (F1 = 6.51, P <
      .05) favored risperidone. CONCLUSIONS: Clozapine-treated partially responsive
      patients were less likely to discontinue treatment for lack of efficacy and
      improved more globally than those treated with risperidone, although psychotic
      symptoms did not differ. These findings suggest that clozapine should not be
      restricted to the most severely ill, treatment-refractory patients; it should be
      considered as an alternative for patients who have some response to other
      antipsychotics, but still experience troubling symptoms.

PMID- 27035872
TI  - Knockdown of WAVE1 enhances apoptosis of leukemia cells by downregulating
      autophagy.
AB  - Chemoresistance of leukemia constitutes a great challenge for successful
      treatment of leukemia. Autophagy has recently attracted increasing attention for
      its role in conferring resistance to various conventional anti-neoplastic
      regiments. In the present study, the authors showed that WAVE1, a member of WASP
      family verprolin-homologous proteins, is a critical regulator of chemoresistance
      during autophagy. It is positively correlated with clinical status in pediatric
      acute myeloblastic leukemia (AML) and leukemia cell lines. The knockdown of WAVE1
      expression decreased autophagy was accompanied by an upregulation of autophagic
      marker microtubule-associated protein light chain 3 (LC3)-II, a degradation of
      SQSTM1/sequestosome 1 (p62) and the formation of autophagosomes. Moreover, a
      suppression of WAVE1 expression increased the sensitivity of leukemia cells to
      chemotherapy and apoptosis, and depletion of WAVE1 expression promoted the
      translocation of Bcl-2 from mitochondria into the cytoplasm. In addition, a
      knockdown of PI3K-III expression significantly inhibited WAVE1-mediated
      autophagy. Furthermore, suppression of WAVE1 expression blocked the interactions
      between Beclin1 and PI3K-III and the disassociation of Beclin1-Bcl-2 during
      enhanced autophagy. The above results suggested that WAVE1 is a critical pro
      autophagic protein capable of enhancing cell survival and regulating
      chemoresistance in leukemia cells potentially through the Beclin1/Bcl-2 and
      Beclin1/PI3K-III complex-dependent pathways. 

PMID- 27035873
TI  - miR-100 suppresses the proliferation and tumor growth of esophageal squamous
      cancer cells via targeting CXCR7.
AB  - MicroRNAs are highly conserved non-coding RNAs that regulate gene expression at
      the post-transcriptional level, and play pivotal roles in cancer development and
      progression. miR-100 has been reported to be significantly downregulated in a
      variety of cancers, including esophageal cancer. However, the role of miR-100 in
      human esophageal cancer has not been fully elucidated. We demonstrated that
      overexpression of miR-100 in esophageal cancer cells markedly inhibited cell
      proliferation, migration and invasion as well as tumor growth. We subsequently
      showed that CXCR7 is a direct target gene of miR-100. Our results indicated that
      miR-100 plays a tumor-suppressor role in esophageal cancer and suggest its
      potential application for esophageal cancer treatment. 

PMID- 27035874
TI  - Translational informatics approach for identifying the functional molecular
      communicators linking coronary artery disease, infection and inflammation.
AB  - Translational informatics approaches are required for the integration of diverse
      and accumulating data to enable the administration of effective translational
      medicine specifically in complex diseases such as coronary artery disease (CAD).
      In the current study, a novel approach for elucidating the association between
      infection, inflammation and CAD was used. Genes for CAD were collected from the
      CAD-gene database and those for infection and inflammation were collected from
      the UniProt database. The cytomegalovirus (CMV)-induced genes were identified
      from the literature and the CAD-associated clinical phenotypes were obtained from
      the Unified Medical Language System. A total of 55 gene ontologies (GO) termed
      functional communicator ontologies were identified in the gene sets linking
      clinical phenotypes in the diseasome network. The network topology analysis
      suggested that important functions including viral entry, cell adhesion,
      apoptosis, inflammatory and immune responses networked with clinical phenotypes.
      Microarray data was extracted from the Gene Expression Omnibus (dataset:
      GSE48060) for highly networked disease myocardial infarction. Further analysis of
      differentially expressed genes and their GO terms suggested that CMV infection
      may trigger a xenobiotic response, oxidative stress, inflammation and immune
      modulation. Notably, the current study identified gamma-glutamyl transferase
      (GGT)-5 as a potential biomarker with an odds ratio of 1.947, which increased to
      2.561 following the addition of CMV and CMV-neutralizing antibody (CMV-NA)
      titers. The C-statistics increased from 0.530 for conventional risk factors
      (CRFs) to 0.711 for GGT in combination with the above mentioned infections and
      CRFs. Therefore, the translational informatics approach used in the current study
      identified a potential molecular mechanism for CMV infection in CAD, and a
      potential biomarker for risk prediction. 

PMID- 27035875
TI  - Curcumin induces G2/M arrest and triggers apoptosis via FoxO1 signaling in U87
      human glioma cells.
AB  - It has previously been demonstrated that curcumin possesses an antitumor
      activity, which is associated with its ability to induce G2/M cell cycle arrest
      and apoptosis. However the detailed underlying mechanisms remain unclear. The
      present study aimed to investigate the efficacy and underlying mechanism of
      curcumin-induced cell cycle arrest and apoptosis in U87 human glioblastoma cells.
      By immunofluorescence staining, subcellular fractionation and western blotting,
      the present study demonstrated that curcumin was able to induce G2/M cell cycle
      arrest and apoptosis by increasing the expression levels of cyclin G2, cleaved
      caspase-3 and Fas ligand (FasL), and decreasing the expression of cyclin
      dependent kinase 1 (CDK1). In addition, increased expression of forkhead box
      protein O1 (FoxO1) and decreased expression of phosphorylated (p)-FoxO1 were
      detected in the curcumin-treated U87 cells. Curcumin was also able to induce the
      translocation of FoxO1 from the cytoplasm to the nucleus. Furthermore, following
      knockdown of FoxO1 expression in curcumin-treated U87 cells using FoxO1 small
      interfering RNA, the expression levels of cyclin G2, cleaved caspase-3 and FasL
      were inhibited; however, the expression levels of CDK1 were not markedly altered.
      Notably, following knockdown of CDK1 expression under normal conditions, the
      total expression of FoxO1 was not affected; however, p-FoxO1 expression was
      decreased and FoxO1 nuclear expression was increased. Furthermore, curcumin
      induced G2/M cell cycle arrest and apoptosis could be attenuated by FoxO1
      knockdown. These results indicated that curcumin may induce G2/M cell cycle
      arrest and apoptosis in U87 cells by increasing FoxO1 expression. The present
      study identified a novel mechanism underlying the antitumor effects of curcumin,
      and may provide a theoretical basis for the application of curcumin in glioma
      treatment. 

PMID- 27035876
TI  - Gene expression profile analysis of pancreatic cancer based on microarray data.
AB  - The present study identified differentially-expressed genes (DEGs) between
      pancreatic cancer (PC) tissues and normal tissues, and assessed genetic factors
      associated with the pathogenesis of PC. The mRNA expression microarray dataset,
      GSE16515, containing 52 samples, including 16 paired tumor and normal tissue
      samples, and 20 tumor samples, was downloaded from Gene Expression Omnibus. Raw
      data were normalized and DEGs were identified. Subsequently, clustering was
      performed, protein-protein interaction networks were drawn, and functional and
      pathway enrichment analyses of the DEGs were performed. Copy number variations of
      DEGs were also identified. A total of 1,765 DEGs between PC and normal tissues
      were identified, including 1,312 upregulated and 453 downregulated DEGs.
      Upregulated DEGs were associated with the regulation of nucleocytoplasmic and
      intracellular transport, whereas downregulated DEGs were associated with the
      response to organic substances and hormone stimulus. The pancreatic cancer
      pathway was connected to three DEGs, namely transforming growth factor beta1
      (TGFB1), TGFbeta receptor 1 (TGFBR1) and epidermal growth factor (EGF), which had
      2, 3 and 5 CNVs, respectively. These results indicated the important roles of
      TGFB1, TGFBR1 and EGF in the pathogenesis of PC. These genes may be potential
      therapeutic targets for the treatment of PC. 

PMID- 27035877
TI  - Tunable optofluidic birefringent lens.
AB  - An optofluidic birefringent lens is demonstrated using hydrodynamic liquid-liquid
      (L(2)) interfaces in a microchannel. The L(2) lens comprises a nematic liquid
      crystal (NLC) phase and an optically isotropic phase for the main stream and the
      surrounding sub-stream, respectively. When the optofluidic device is subjected to
      a sufficiently strong electric field perpendicular to the flow direction, NLCs
      are allowed to orient along the external field rather than the flow direction
      overcoming fluidic viscous stress. The characteristics of the optofluidic
      birefringence lens are investigated by experimental and numerical analyses. The
      difference between the refractive indices of the main stream and the sub-stream
      changes according to the polarization direction of incident light, which
      determines the optical behaviour of the lens. The incidence of s-polarized light
      leads to a short focal point, while p-polarized light has a relatively long focal
      distance from the same L(2) interface. The curvatures and focal lengths of the
      lens are successfully evaluated by a hydrodynamic theory of NLCs and a simple ray
      tracing model.

PMID- 27035879
TI  - Amine-Ligated Approach for the Synthesis of Extra-Large-Pore Zinc Phosphites with
      qtz-h and bnn Topologies.
AB  - Presented here are two open-framework zinc phosphites, namely, Zn(dabco)0.5(HPO3)
      (SCU-18) and Zn4(Hdabco)2(CH3COO)2(HPO3)4 (SCU-20), where dabco = 1,4
      diazabicyclo[2.2.2]octane. SCU-18 features a rare 3-connected inorganic skeleton
      with a chiral qtz-h topology. It contains 18-membered-ring (18 MR) channels
      displaying porosity and second-harmonic-generation response. SCU-20 has a bnn
      topology containing large 20 MR channels that shows a strong blue emission as a
      result of excitation at 375 nm. 

PMID- 27035878
TI  - Ablation of Glutaredoxin-1 Modulates House Dust Mite-Induced Allergic Airways
      Disease in Mice.
AB  - Protein S-glutathionylation (PSSG) is an oxidant-induced post-translational
      modification of protein cysteines that impacts structure and function. The
      oxidoreductase glutaredoxin-1 (Glrx1) under physiological conditions catalyzes
      deglutathionylation and restores the protein thiol group. The involvement of
      Glrx1/PSSG in allergic inflammation induced by asthma-relevant allergens remains
      unknown. In the present study, we examined the impact of genetic ablation of
      Glrx1 in the pathogenesis of house dust mite (HDM)-induced allergic airways
      disease in mice. Wild-type (WT) or Glrx1(-/-) mice were instilled intranasally
      with HDM on 5 consecutive days for 3 weeks. As expected, overall PSSG was
      increased in Glrx1(-/-) HDM mice as compared with WT animals. Total cells in
      bronchoalveolar lavage fluid were similarly increased in HDM-treated WT and
      Glrx1(-/-) mice. However, in response to HDM, mice lacking Glrx1 demonstrated
      significantly more neutrophils and macrophages but fewer eosinophils as compared
      with HDM-exposed WT mice. mRNA expression of the Th2-associated cytokines IL-13
      and IL-6, as well as mucin-5AC (Muc5ac), was significantly attenuated in Glrx1(-/
      ) HDM-treated mice. Conversely, mRNA expression of IFN-gamma and IL-17A was
      increased in Glrx1(-/-) HDM mice compared with WT littermates. Restimulation of
      single-cell suspensions isolated from lungs or spleens with HDM resulted in
      enhanced IL-17A and decreased IL-5 production in cells derived from inflamed
      Glrx1(-/-) mice compared with WT animals. Finally, HDM-induced tissue damping and
      elastance were significantly attenuated in Glrx1(-/-) mice compared with WT
      littermates. These results demonstrate that the Glrx1-PSSG axis plays a pivotal
      role in HDM-induced allergic airways disease in association with enhanced type 2
      inflammation and restriction of IFN-gamma and IL-17A.

PMID- 27035880
TI  - Resistance of mitochondrial DNA-depleted cells against oxidized low-density
      lipoprotein-induced macrophage pyroptosis.
AB  - Oxidized low-density lipoprotein (Ox-LDL)-induced macrophage pyroptosis is
      critical in atherosclerosis inflammation and plaque instability. It has been
      reported that mitochondrial (mt)DNA-depleted (rho0) cells demonstrate resistance
      to apoptosis. However, little is known about the susceptibility of rho0 cells to
      Ox-LDL-induced macrophage pyroptosis. Pyroptosis, a caspase-1-dependent
      programmed cell death, which compromises membrane integrity, cleaves pro
      interleukin (IL)-1beta and pro-IL-18 into IL-1beta and IL-18, respectively and
      releases damage-associated molecular pattern molecules, is triggered by a variety
      of stimuli, including Ox-LDL. In the present study, the expression levels of
      cleaved caspase-1 and IL-1beta in Ox-LDL-treated J774A.1 rho0 cells were observed
      to be significantly decreased when compared with Ox-LDL-treated J774A.1 normal
      cells. Furthermore, J774A.1 rho0 cells exhibited a significant reduction in the
      ratios of dead cells and lactate dehydrogenase release following Ox-LDL
      stimulation compared with the J774A.1 normal cells. In addition, the loss of
      mtDNA did not influence Ox-LDL-induced cholesterol accumulation in J774A.1 rho0
      cells, which was observed by Oil Red O staining and CHOD-PAP assay. Finally,
      J774A.1 rho0 cells exhibited reduced reactive oxygen species (ROS) production and
      were capable of maintaining the mitochondrial membrane potential following Ox-LDL
      treatment. Thus, the results indicate that the loss of mtDNA potentially rendered
      murine macrophage J774A.1 resistant to Ox-LDL-induced pyroptosis by mitigating
      NACHT, LRR and PYD domains-containing protein 3 inflammasome activation through
      reducing ROS production. In addition, mtDNA depletion did not interrupt Ox-LDL
      induced intracellular lipid accumulation and continued to maintain the
      mitochondrial membrane potential. 

PMID- 27035881
TI  - Pollen Overload: Seasonal Allergies in a Changing Climate.

PMID- 27035882
TI  - Effect of green tea catechins on gastric mucosal dysplasia in insulin-gastrin
      mice.
AB  - Green tea catechins (GTCs) have been implicated in various physiological effects,
      including anti-carcinogenic activities. In the present study, we evaluated the
      effects of GTCs specifically on the development of gastritis and pre-malignant
      lesions in insulin-gastrin mice. Nine-week-old male INS-GAS mice (n=38) were
      supplemented with GTCs for 4 and 28 weeks, and their body weights, serum gastrin
      levels, histopathology and pro-inflammatory cytokine levels in gastric tissue and
      mucosal cell proliferation were monitored. Body weights of the GTC-treated mice
      were significantly lower than those of the untreated controls (P<=0.05). Serum
      gastrin levels were suppressed at the age of 37-weeks (P<=0.05). The
      histopathological scores indicated that the extent of dysplasia was significantly
      diminished (P<=0.05), although GTC supplementation did not affect the
      inflammation scores. The messenger RNA levels of interferon (IFN)-gamma were
      significantly reduced at the age of 13 weeks (P<=0.05), although the changes did
      not reach statistical significance at the age of 37 weeks (P=0.056). The labeling
      index of Ki-67 immunohistochemistry was significantly decreased (P<=0.05). These
      results demonstrated that GTCs may play a protective role in the development of
      gastritis and pre-malignant lesions via an IFN-gamma, gastrin, and mucosal cell
      proliferation-dependent mechanism in this rodent model and potentially in humans.

PMID- 27035883
TI  - Epithelial protein lost in neoplasm-alpha (EPLIN-alpha) is a potential prognostic
      marker for the progression of epithelial ovarian cancer.
AB  - Epithelial protein lost in neoplasm-alpha (EPLIN-alpha) is a cytoskeletal protein
      whose expression is often lost or is aberrant in cancerous cells and tissues and
      whose loss is believed to be involved in aggressive phenotypes. This study
      examined this molecule in human epithelial ovarian tissues and investigated the
      cellular impact of EPLIN-alpha on ovarian cancer cells (EOC), SKOV3 and COV504.
      The expression of EPLIN-alpha in human ovarian tissues and EOC was assessed at
      both the mRNA and protein levels using reverse transcription-PCR (RT-PCR) and
      immunohistochemistry, respectively. In vitro assays for cellular matrix adhesion
      and migration (confirmed by an electrical cell substrate impedance sensing (ECIS)
      based method), invasion and cell growth were employed in order to assess the
      biological influence of EPLIN-alpha expression on EOC cells. Immunohistochemical
      analysis of ovarian cancer samples demonstrated that only a small number
      expressed EPLIN-alpha protein. Downregulation of EPLIN-alpha protein in EOC cell
      lines increased the growth, invasion, adhesion and migration in vitro. This EPLIN
      alpha downregulation may have a prognostic value. From these data, we conclude
      that downregulation of EPLIN-alpha may be associated with poorer patient
      prognosis, and that this molecule appears to play a tumour suppressor role by
      inhibition of EOC growth and migration. 

PMID- 27035884
TI  - Role of extracellular signal-regulated kinase 1/2 signal transduction pathway in
      insulin secretion by beta-TC6 cells.
AB  - The present study aimed to investigate the role of the extracellular signal
      regulated kinase (ERK)1/2 signal transduction pathway in glucose-stimulated
      insulin secretion in beta-TC6 mouse pancreatic cells. Insulin production by beta
      TC6 cells was stimulated with various concentrations of glucose, which was dose
      dependently inhibited by mitogen-activated protein kinase inhibitor PD98059, as
      indicated by a radioimmunoassay. Furthermore, glucose stimulation enhanced the
      phosphorylation of ERK1/2, which was dose-dependently inhibited by PD98059, as
      indicated by western blot analysis. These results indicated that the activation
      of the ERK1/2 signal transduction pathway may have an important role in glucose
      stimulated insulin secretion in beta-TC6 cells. 

PMID- 27035885
TI  - Role of the ERK1/2 pathway in osmolarity effects on nucleus pulposus cell
      apoptosis in a disc perfusion culture.
AB  - Osmolarity fluctuations are inevitable within the nucleus pulposus (NP). However,
      the effects of osmolarity on NP cell apoptosis within the organ-cultured disc
      remain unclear. The objective of this study was to investigate effects of
      different osmolarity levels (hypo-, iso-, and hyper-) and osmolarity modes
      (constant and cyclic) on NP cell apoptosis in a disc perfusion culture and to
      study the role of the ERK1/2 pathway in this regulatory process. Porcine discs
      were cultured for 7 days in different osmotic medium, including constant hypo-,
      iso-, and hyper-osmolarity (330, 430, and 550 mOsm/L, respectively) and cyclic
      osmolarity (430 mOsm/L for 8 h, followed by 550 mOsm/L for 16 h). The role of the
      ERK1/2 pathway was investigated by using the pharmacological inhibitor U0126. NP
      cell apoptosis was analyzed by TUNEL staining, caspase-3 activity, gene
      expression of Bcl-2, Bax and caspase-3 and protein expression of cleaved caspase
      3, and cleaved PARP. Our results showed that NP cell apoptosis was increased in
      hypo- and hyper-osmolarity cultures compared to iso- or cyclic-osmolarity
      culture, whereas the level of apoptosis in the iso-osmolarity culture was lower
      than that in the cyclic-osmolarity culture. When the ERK1/2 pathway was inhibited
      in the iso- and cyclic-osmolarity cultures, the level of NP cell apoptosis was
      significantly increased. In conclusion, the effects of osmolarity on NP cell
      apoptosis depend on the osmolarity level (hypo-, iso-, or hyper-) and osmolarity
      mode (constant or cyclic). Futhermore, inhibition of the ERK1/2 pathway promotes
      NP cell apoptosis in this process. (c) 2016 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 35:86-92, 2017.

PMID- 27035886
TI  - Feasibility of HIV Pre-Exposure Prophylaxis as Part of Routine Care in Toronto,
      Canada.

PMID- 27035887
TI  - Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney
      Disease in Children and Youth With Perinatal HIV Infection.
AB  - APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in
      adults, with the strongest effect being for HIV-associated nephropathy. Their
      role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a
      nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS
      Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high
      risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2
      to 10.0]. We report an unadjusted incidence of 1.2 CKD cases/100 person-years
      (95% CI: 0.5 to 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with
      important implications for sub-Saharan Africa.

PMID- 27035888
TI  - HIV stigma trends in the general population during antiretroviral treatment
      expansion: analysis of 31 countries in sub-Saharan Africa, 2003-2013.
AB  - BACKGROUND: HIV-related stigma is associated with increased risk-taking behavior,
      reduced uptake of HIV testing, and decreased adherence to antiretroviral therapy
      (ART). Although ART scale-up may reduce HIV-related stigma, the extent to which
      levels of stigma in the general population have changed during the era of ART
      scale-up in sub-Saharan Africa is unknown. METHODS: Social distance and
      anticipated stigma were operationalized using standard HIV-related stigma
      questions contained in the Demographic and Health Surveys and AIDS Indicator
      Surveys of 31 African countries between 2003 and 2013. We fitted multivariable
      linear regression models with cluster-correlated robust standard errors and
      country fixed effects, specifying social distance or anticipated stigma as the
      dependent variable and year as the primary explanatory variable of interest.
      RESULTS: We estimated a statistically significant negative association between
      year and desires for social distance (b = -0.020; P < 0.001; 95% confidence
      interval: -0.026 to -0.015) but a statistically significant positive association
      between year and anticipated stigma (b = 0.023; P < 0.001; 95% confidence
      interval: 0.018 to 0.027). In analyses stratified by HIV prevalence above or
      below the sample median, declines in social distancing over time were more
      pronounced among countries with a higher HIV prevalence. CONCLUSIONS: Concomitant
      with ART scale-up in sub-Saharan Africa, anticipated stigma in the general
      population increased despite a decrease in social distancing toward people living
      with HIV. Although ART scale-up may help reduce social distancing toward people
      living with HIV, particularly in high-prevalence countries, other interventions
      targeting symbolic or instrumental concerns about HIV may be needed.

PMID- 27035889
TI  - Lightweight and Easily Foldable MCMB-MWCNTs Composite Paper with Exceptional
      Electromagnetic Interference Shielding.
AB  - Lightweight and easily foldable with high conductivity, multiwalled carbon
      nanotube (MWCNT)-based mesocarbon microbead (MCMB) composite paper is prepared
      using a simple, efficient, and cost-effective strategy. The developed lightweight
      and conductive composite paper have been reported for the first time as an
      efficient electromagnetic interference (EMI) shielding material in X-band
      frequency region having a low density of 0.26 g/cm(3). The investigation revealed
      that composite paper shows an excellent absorption dominated EMI shielding
      effectiveness (SE) of -31 to -56 dB at 0.15-0.6 mm thickness, respectively.
      Specific EMI-SE of as high as -215 dB cm(3)/g exceeds the best values of metal
      and other low-density carbon-based composites. Additionally, lightweight and
      easily foldable ability of this composite paper will help in providing stable EMI
      shielding values even after constant bending. Such intriguing performances open
      the framework to designing a lightweight and easily foldable composite paper as
      promising EMI shielding material, especially in next-generation devices and for
      defense industries.

PMID- 27035890
TI  - On the mechanism of biological activation by tritium.
AB  - The mechanism of biological activation by beta-emitting radionuclide tritium was
      studied. Luminous marine bacteria were used as a bioassay to monitor the
      biological effect of tritium with luminescence intensity as the physiological
      parameter tested. Two different types of tritium sources were used: HTO molecules
      distributed regularly in the surrounding aqueous medium, and a solid source with
      tritium atoms fixed on its surface (tritium-labeled films, 0.11, 0.28, 0.91, and
      2.36 MBq/cm(2)). When using the tritium-labeled films, tritium penetration into
      the cells was prevented. The both types of tritium sources revealed similar
      changes in the bacterial luminescence kinetics: a delay period followed by
      bioluminescence activation. No monotonic dependences of bioluminescence
      activation efficiency on specific radioactivities of the films were found. A 15
      day exposure to tritiated water (100 MBq/L) did not reveal mutations in bacterial
      DNA. The results obtained give preference to a "non-genomic" mechanism of
      bioluminescence activation by tritium. An activation of the intracellular
      bioluminescence process develops without penetration of tritium atoms into the
      cells and can be caused by intensification of trans-membrane cellular processes
      stimulated by ionization and radiolysis of aqueous media. 

PMID- 27035892
TI  - Bare metal stenting of the iliac arteries.
AB  - A significant subset of patients with peripheral artery disease (PAD) has iliac
      artery involvement that requires treatment. The development of bare metal stents
      has improved the short- and long-term outcomes of endovascular repair and has
      become first line therapy. Open surgical bypass has been reserved for extremely
      complex anatomic morphologies or endovascular failures. It is unclear whether
      primary stenting is superior to angioplasty with provisional stenting but if
      angioplasty is used alone, it is likely only appropriate for the most focal
      lesions. Self-expanding and balloon-expandable stents have unique characteristics
      that are suitable to different lesion morphologies. Both stent-types have
      demonstrated similar outcomes. Herein, we review the practice and results of bare
      metal stents in the iliac arteries. 

PMID- 27035893
TI  - Mitral valve repair versus replacement: is it a different story for percutaneous
      compared to surgical valve therapy?
AB  - The complementary role of mitral valve repair versus replacement is based on
      evidence of long-term results in open surgery. Transcatheter mitral valve repair
      and replacement are both under rapid development but subject to clinical
      feasibility and first in-human short- and midterm outcome studies. The present
      article aims to review mitral valve repair and replacement by both techniques and
      to elucidate similar and potentially different aspects among the open and
      interventional approach. 

PMID- 27035894
TI  - Nasal administration of interleukin-33 induces airways angiogenesis and
      expression of multiple angiogenic factors in a murine asthma surrogate.
AB  - The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been
      implicated in asthma pathogenesis. Angiogenesis is a feature of airways
      remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis
      and expression of angiogenic factors in an established murine surrogate of
      asthma. In the present study, BALB/c mice were subjected to serial intranasal
      challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) 
      sensitized mice were subjected to serial intranasal challenge with OVA or normal
      saline to serve as positive and negative controls, respectively.
      Immunohistochemical analysis of expression of von Willebrand factor and
      erythroblast transformation-specific-related gene, both blood vessel markers, and
      angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1,
      epidermal growth factor and amphiregulin was performed in lung sections ex vivo.
      An established in-house assay was used to test whether IL-33 was able to induce
      microvessel formation by human vascular endothelial cells. Results showed that
      serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation
      of peribronchial von Willebrand factor-positive blood vessels to a degree closely
      related to the total expression of the angiogenic factors amphiregulin,
      angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor
      1. IL-33 also induced microvessel formation by human endothelial cells in a
      concentration-dependent fashion in vitro. Our data are consistent with the
      hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by
      increasing local expression of multiple angiogenic factors in an allergen
      independent murine asthma surrogate, and consequently that IL-33 or its receptor
      is a potential novel molecular target for asthma therapy.

PMID- 27035895
TI  - Conjugation, Substituent, and Solvent Effects on the Photogeneration of Quinone
      Methides.
AB  - 4- and 5-arylethynyl water-soluble Mannich bases and related quaternary ammonium
      salts were synthesized and investigated as a model of conjugated quinone methide
      precursors (QMPs) by UV-vis light activation. Preparative photohydration and
      trapping reactions by thiols were studied, together with the detection of both
      transient QMs and competing QMP lowest triplet excited states (T1), by laser
      flash photolysis. The efficiency of the arylethynyl derivatives as QMPs was
      remarkably affected by structural features (i.e., conjugating arylethynyl
      moieties, substituents, and leaving groups) and protic vs aprotic solvation. Our
      collective data clarify the dichotomy in the photoreactivity of conjugated
      Mannich bases and related quaternary ammonium salts as alkylating agents and
      singlet oxygen sensitizers.

PMID- 27035896
TI  - Update on monitoring and adverse effects of first generation disease modifying
      therapies and their recently approved versions in relapsing forms of multiple
      sclerosis.
AB  - PURPOSE OF REVIEW: As of April 2015, 13 disease modifying therapies (DMTs) have
      been approved by the Food and Drug Administration. The older agents continue to
      be utilized across the globe, especially in developing countries where many newer
      DMTs are still not available. Even though first generation DMTs have modest
      efficacy they have long term safety profile, and are considered safer than the
      second generation DMTs. RECENT FINDINGS: A PEGylated interferon beta-1a
      preparation that is administered subcutaneously every 2 weeks was also recently
      approved. Less frequent administration potentially reduced administration
      associated side effects and may improve adherence and compliance. The
      polyethylene glycol is also thought to make the drug less immunogenic. Glatopa (a
      glatiramer acetate bioequivalent), now represents the first available generic
      alternative of a DMT for multiple sclerosis. Its dosing, route of administration,
      and side effects are the same as for Copaxone. SUMMARY: In this article, we
      review the potential adverse effects and recommended laboratory studies as part
      of the monitoring strategy following initiation of various first generation DMTs
      and their recently approved versions.

PMID- 27035897
TI  - Repair strategies for multiple sclerosis: challenges, achievements and
      perspectives.
AB  - PURPOSE OF REVIEW: Despite major progress in multiple sclerosis (MS) treatment,
      to date, accumulation of irreversible clinical disability is not sufficiently
      prevented with immunotherapies. In this context, repair strategies aimed at
      reducing axonal damage are becoming a very active field of preclinical and
      clinical research. RECENT FINDINGS: Improved understanding of the cellular and
      molecular mechanisms of myelin repair, together with the emergence of new
      therapeutic candidates are paving the way for novel therapeutic strategies in MS.
      In parallel, there is a very active development of imaging methods to assess
      lesions ongoing remyelination that are crucially needed to evaluate therapeutic
      efficacy. SUMMARY: The current development of a very dynamic and
      multidisciplinary research on remyelination should accelerate the development of
      myelin repair strategies in MS, to prevent disability progression.

PMID- 27035898
TI  - Recent achievements in stem cell-mediated myelin repair.
AB  - PURPOSE OF REVIEW: Following the establishment of a number of successful
      immunomodulatory treatments for multiple sclerosis, current research focuses on
      the repair of existing damage. RECENT FINDINGS: Promotion of regeneration is
      particularly important for demyelinated areas with degenerated or functionally
      impaired axons of the central nervous system's white and gray matter. As the
      protection and generation of new oligodendrocytes is a key to the re
      establishment of functional connections, adult oligodendrogenesis and myelin
      reconstitution processes are of primary interest. Moreover, understanding,
      supporting and promoting endogenous repair activities such as mediated by
      resident oligodendroglial precursor or adult neural stem cells are currently
      thought to be a promising approach toward the development of novel regenerative
      therapies. SUMMARY: This review summarizes recent developments and findings
      related to pharmacological myelin repair as well as to the modulation/application
      of stem cells with the aim to restore defective myelin sheaths.

PMID- 27035899
TI  - Environmental factors and their interactions with risk genotypes in MS
      susceptibility.
AB  - PURPOSE OF REVIEW: The area of multiple sclerosis (MS) epidemiology has expanded
      during the last few years. Established lifestyle and environmental factors
      influencing MS risk are Epstein-Barr virus infection, sun exposure/vitamin D, and
      smoking. We review these factors and a series of other potential candidates
      implicated in the pathogenesis of MS and how environmental factors interact with
      genetic susceptibility with regard to disease risk. RECENT FINDINGS: On top of
      established MS-associated factors, there is now strong evidence for influence of
      adolescent obesity, exposure to organic solvents and shift work, all
      demonstrating increased risk of disease. Other factors, such as nicotine,
      alcohol, and high coffee consumption are associated with decreased MS risk. A
      number of lifestyle/environmental factors, including smoking and obesity, seem to
      interact with MS risk human leukocyte antigen genes, conferring much stronger
      effects on disease risk among those exposed to both factors. Furthermore, an
      interaction between two environmental factors, obesity and infectious
      mononucleosis, with regard to MS risk, has been demonstrated in two independent
      studies. SUMMARY: MS is a complex disease for which both genetic susceptibility
      and lifestyle/environmental factors are important, and where the latter may be of
      great importance. Lifestyle and environmental factors can often be modified and
      may denote pathogenic pathways.

PMID- 27035900
TI  - Optic neuritis as a phase 2 paradigm for neuroprotection therapies of multiple
      sclerosis: update on current trials and perspectives.
AB  - PURPOSE OF REVIEW: In multiple sclerosis as the most common inflammatory
      demyelinating disease in Western countries, major therapeutic success has been
      achieved with regard to strategies targeting immunological master switches. These
      approaches effectively reduce inflammatory disease activity but fail to address
      ongoing neurodegeneration or disturbed regeneration. However, intense research
      efforts investigating molecular mechanisms of disease have identified 'druggable'
      targets for prevention of inflammatory neurodegeneration and disturbed
      regeneration. This review covers recent developments in clinical trials using
      optic neuritis as a model for screening such neuroprotective and
      neuroregenerative therapeutic approaches. RECENT FINDINGS: Optic neuritis has
      been used in a series of recent pilot studies investigating the effects of
      erythropoietin, simvastatin, autologous mesenchymal stem cells, phenytoin, as
      well as blockade of LINGO-1 (opicinumab). Of note, these studies applied novel
      outcome measures related to function and structure of the visual pathway,
      including optical coherence tomography, full-field visual-evoked potentials,
      multifocal visual-evoked potential, high as well as low-contrast visual acuity.
      Comparison of these different approaches reveals novel insights into short-term
      evolution of neurobiological effects during optic neuritis and the window of
      opportunity for therapeutic interventions. SUMMARY: Translation of
      neuroprotective and neuroregenerative approaches to clinical reality represents a
      huge challenge. Optic neuritis as a prototypic autoimmune demyelinating disease
      offers an option for testing new therapies targeting key deleterious processes in
      multiple sclerosis.

PMID- 27035901
TI  - Central nervous system inflammation across the age span.
AB  - PURPOSE OF REVIEW: This article reviews the influence of age on the development
      and course of central nervous system (CNS) inflammatory diseases and relates
      these to genetic and epidemiologic factors and to the age-related properties of
      both the immune and nervous systems and their interactions. RECENT FINDINGS:
      There is increased recognition of the onset of multiple sclerosis, the prototype
      CNS inflammatory/demyelinating disease, outside the expected peak age in young
      adults. Study of childhood-onset MS cases with comparison to those with uniphasic
      acquired inflammatory demyelinating syndromes, has helped to better define the
      clinical spectrum of both types of disorders and provides opportunities to define
      mechanisms linking recognized genetic and environmental risk factors and disease.
      Studies of late-onset cases implicate the enhanced role of innate immune
      mechanisms and immune responses compartmentalized within the CNS in driving a
      more progressive disease course. The influence of age on incidence and course of
      multiple sclerosis is compared with the wider spectrum of CNS inflammatory
      disorders with identified pathogenic mechanisms. SUMMARY: Intrinsic properties of
      the immune and nervous systems, coupled with the impacts on these systems by
      environmental factors and by the consequences of CNS tissue injury, underlie the
      age-related differences in incidence and course of inflammatory/demyelinating
      disorders of the CNS.

PMID- 27035902
TI  - A surprising switch in absolute configuration of anti-inflammatory macrolactones.
AB  - Oxacyclododecindione-type macrolactones exhibit highly potent anti-inflammatory
      activities even at nanomolar concentration. After the determination of the
      relative configuration of the stereocenters at C14 and C15 by total synthesis of
      4-dechloro-14-deoxyoxacyclododecindione and 14-deoxyoxacyclododecindione, the
      absolute configuration has now been assigned by X-ray crystallography.
      Surprisingly, the absolute configuration is (14S,15R) which differs for C15 from
      that of the well-known derivatives of (S)-curvularin. The biological activities
      of both enantiomers of 14-deoxyoxacyclododecindione, obtained by racemic
      synthesis and optical resolution, were investigated and the ring conformation of
      the natural product was compared to that of (S)-curvularin and (R)
      dehydrocurvularin. 

PMID- 27035903
TI  - HER2+ Cancer Cell Dependence on PI3K vs. MAPK Signaling Axes Is Determined by
      Expression of EGFR, ERBB3 and CDKN1B.
AB  - Understanding the molecular pathways by which oncogenes drive cancerous cell
      growth, and how dependence on such pathways varies between tumors could be highly
      valuable for the design of anti-cancer treatment strategies. In this work we
      study how dependence upon the canonical PI3K and MAPK cascades varies across
      HER2+ cancers, and define biomarkers predictive of pathway dependencies. A panel
      of 18 HER2+ (ERBB2-amplified) cell lines representing a variety of indications
      was used to characterize the functional and molecular diversity within this
      oncogene-defined cancer. PI3K and MAPK-pathway dependencies were quantified by
      measuring in vitro cell growth responses to combinations of AKT (MK2206) and MEK
      (GSK1120212; trametinib) inhibitors, in the presence and absence of the ERBB3
      ligand heregulin (NRG1). A combination of three protein measurements comprising
      the receptors EGFR, ERBB3 (HER3), and the cyclin-dependent kinase inhibitor p27
      (CDKN1B) was found to accurately predict dependence on PI3K/AKT vs. MAPK/ERK
      signaling axes. Notably, this multivariate classifier outperformed the more
      intuitive and clinically employed metrics, such as expression of phospho-AKT and
      phospho-ERK, and PI3K pathway mutations (PIK3CA, PTEN, and PIK3R1). In both cell
      lines and primary patient samples, we observed consistent expression patterns of
      these biomarkers varies by cancer indication, such that ERBB3 and CDKN1B
      expression are relatively high in breast tumors while EGFR expression is
      relatively high in other indications. The predictability of the three protein
      biomarkers for differentiating PI3K/AKT vs. MAPK dependence in HER2+ cancers was
      confirmed using external datasets (Project Achilles and GDSC), again out
      performing clinically used genetic markers. Measurement of this minimal set of
      three protein biomarkers could thus inform treatment, and predict mechanisms of
      drug resistance in HER2+ cancers. More generally, our results show a single
      oncogenic transformation can have differing effects on cell signaling and growth,
      contingent upon the molecular and cellular context. 

PMID- 27035904
TI  - Network Diversity and Affect Dynamics: The Role of Personality Traits.
AB  - People divide their time unequally among their social contacts due to time
      constraints and varying strength of relationships. It was found that high
      diversity of social communication, dividing time more evenly among social
      contacts, is correlated with economic well-being both at macro and micro levels.
      Besides economic well-being, it is not clear how the diversity of social
      communication is also associated with the two components of individuals'
      subjective well-being, positive and negative affect. Specifically, positive
      affect and negative affect are two independent dimensions representing the
      experience (feeling) of emotions. In this paper, we investigate the relationship
      between the daily diversity of social communication and dynamic affect states
      that people experience in their daily lives. We collected two high-resolution
      datasets that capture affect scores via daily experience sampling surveys and
      social interaction through wearable sensing technologies: sociometric badges for
      face-to-face interaction and smart phones for mobile phone calls. We found that
      communication diversity correlates with desirable affect states--e.g. an increase
      in the positive affect state or a decrease in the negative affect state--for some
      personality types, but correlates with undesirable affect states for others. For
      example, diversity in phone calls is experienced as good by introverts, but bad
      by extroverts; diversity in face-to-face interaction is experienced as good by
      people who tend to be positive by nature (trait) but bad for people who tend to
      be not positive by nature. More broadly, the moderating effect of personality
      type on the relationship between diversity and affect was detected without any
      knowledge of the type of social tie or the content of communication. This
      provides further support for the power of unobtrusive sensing in understanding
      social dynamics, and in measuring the effect of potential interventions designed
      to improve well-being.

PMID- 27035906
TI  - Can calcified pulmonary metastases detected by (18)F-FDG PET/CT suggest the
      primary tumor?
AB  - Many calcified nodules are encountered on the (18)F-FDG PET/CT scan and even
      though most of them are benign, the possibility of calcified pulmonary metastases
      (CPM) should be considered. The CT portion can often differentiate benign
      diseases due to their morphology. Measuring SUVmax is very important.
      Understanding the mechanism of calcification in malignant metastatic pulmonary
      lesions may be useful to suggest their origin. 

PMID- 27035905
TI  - Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and
      Viral Suppression among Adolescents and Young Adults Living with HIV.
AB  - BACKGROUND: The authors examined associations between structural characteristics
      and HIV disease management among a geographically diverse sample of behaviorally
      and perinatally HIV-infected adolescents and young adults in the United States.
      METHODS: The sample included 1891 adolescents and young adults living with HIV
      (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care
      through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units.
      All completed audio computer-assisted self-interview surveys. Chart abstraction
      or blood draw provided viral load data. Geographic-level variables were extracted
      from the United States Census Bureau (e.g., socioeconomic disadvantage, percent
      of Black and Latino households, percent rural) and Esri Crime (e.g., global crime
      index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of
      HIV among youth) were extracted at the county-level. Using HLM v.7, the authors
      conducted means-as-outcomes random effects multi-level models to examine the
      association between structural-level and individual-level factors and (1) being
      on antiretroviral therapy (ART) currently; (2) being on ART for at least 6
      months; (3) missed HIV care appointments (not having missed any vs. having missed
      one or more appointments) over the past 12 months; and (4) viral suppression
      (defined by the corresponding assay cutoff for the lower limit of viral load at
      each participating site which denoted nondetectability vs. detectability).
      RESULTS: Frequencies for the 4 primary outcomes were as follows: current ART use
      (n = 1120, 59.23%); ART use for >=6 months (n = 861, 45.53%); at least one missed
      HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%).
      After adjusting for individual-level factors, youth living in more disadvantaged
      areas (defined by a composite score derived from 2010 Census indicators including
      percent poverty, percent receiving public assistance, percent of female, single
      headed households, percent unemployment, and percent of people with less than a
      high school degree) were less likely to report current ART use (OR: 0.85, 95% CI:
      0.72-1.00, p = .05). Among current ART users, living in more disadvantaged areas
      was associated with greater likelihood of having used ART for >=6 months.
      Participants living in counties with greater HIV prevalence among 13-24 year olds
      were more likely to report current ART use (OR: 1.32, 95% CI: 1.05-1.65, p =
      .02), >=6 months ART use (OR: 1.32, 95% CI: 1.05-1.65, p = .02), and to be
      virally suppressed (OR: 1.50, 95% CI: 1.20-1.87, p = .001); however, youth in
      these areas were also more likely to report missed medical appointments (OR:
      1.32, 95% CI: 1.07-1.63, p = .008). CONCLUSIONS: The findings underscore the
      multi-level and structural factors associated with ART use, missed HIV care
      appointments, and viral suppression for adolescents and young adults in the
      United States. Consideration of these factors is strongly recommended in future
      intervention, clinical practice, and policy research that seek to understand the
      contextual influences on individuals' health behaviors.

PMID- 27035907
TI  - Johann Sebastian Bach's "Goldberg variations" to treat insomnia from renal
      lithiasis pain. Sleep research in Nuclear Medicine.

PMID- 27035908
TI  - Echocardiography versus (201)Tl semi-quantitative gated single photon emission
      tomography for the evaluation of cardiac disease associated with late stage
      Duchenne muscular dystrophy.
AB  - OBJECTIVE: In Duchenne muscular dystrophy (DMD) patients cardiac abnormalities
      are often detected. In adult DMD patients cardiac disease (CD) is a cause of
      death which increases by age and is related to respiratory dysfunction. Studies
      have demonstrated that CD in early DMD can be detected by echocardiography (EC)
      or semi-quantitative gated single photon emission tomography ((201)Tl SQGS), and
      the accuracy of these two tests is similar. As the disease advances, evaluation
      of CD by EC becomes difficult due to thoracic deformity and scoliosis. We
      compared (201)Tl SQGS and EC in the evaluation of cardiac function in late stage
      DMD, based on the ejection fraction (EF) value calculated by both tests. Twenty
      three males with late stage DMD, 12 to 35 years of age (22.2+/-7.5), were studied
      by (201)Tl SQGS and EC. The mean EF value by (201)Tl SQGS was 60.8%+/-14.1%,
      which differed from that obtained by EC (52.7%+/-9.8%, P=0.003). Eleven patients
      less than 20 years old did not demonstrate a significant difference between the
      two tests (P=0.06), however, 12 patients over 20 years of age had significantly
      different results between tests (P=0.002). CONCLUSION: Although our patients were
      few we indicated that in DMD patients, aged older than 20 years, at an advanced
      stage of the disease, the EF values calculated by EC were lower than those by
      (201)Tl SQGS possibly due to thoracic deformity.

PMID- 27035909
TI  - [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].
AB  - Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of
      neoplasms with a common embryological origin and diverse biological behavior,
      derived from cells of the neuroendocrine system, the system APUD (amine precursor
      uptake and decarboxylation). They are characterized by overexpression of all five
      somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical
      resection of the tumor is the treatment option, with a possibility of complete
      remission in patients with limited disease. Somatostatin analogs (octreotide and
      lanreotide) are the treatment of choice in patients with residual disease,
      particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is
      administered primarily to patients with poorly differentiated carcinomas. PRRT
      treatment is recommended in case of non-responsiveness of the disease. The ideal
      candidates for PRRT are patients with unresectable disease of high and
      intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111
      ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi),
      are selectively concentrated in the tumor cells, causing maximum tissue damage to
      tumors and with fewer effects on healthy tissue and the immune system. In the
      current review, it was demonstrated that patients with unresectable grade 1 or 2
      disease showed increased PFS (progression free survival) and OS (overall
      survival), while quality of life was improved after PRRT treatment as compared to
      somatostatin analogs, chemotherapy and other targeted therapies.

PMID- 27035910
TI  - A ring closing metathesis strategy for carbapyranosides of xylose and arabinose.
AB  - The synthesis of beta-carba-xylo and arabino pyranosides of cholestanol is
      described. The synthetic strategy, which is analogous to the Postema approach to
      C-glycosides, centers on the ring closing metathesis of an enol ether-alkene
      precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside
      via hydroboration-oxidation on the olefin. The method, which is attractive for
      its modularity and stereoselectivity, may find wider applications to carba
      hexopyranosides and other complex cycloalkyl ether frameworks. 

PMID- 27035911
TI  - Comparative structural characterization of 7 commercial galacto-oligosaccharide
      (GOS) products.
AB  - Many beta-galactosidase enzymes convert lactose into a mixture of galacto
      oligosaccharides (GOS) when incubated under the right conditions. Recently, the
      composition of commercial Vivinal GOS produced by Bacillus circulans beta
      galactosidase was studied in much detail in another study by van Leeuwen et al.
      As a spin-off of this study, we used the developed analytical strategy for the
      evaluation of 6 anonymous commercial GOS products, in comparison with Vivinal
      GOS. These GOS products were first subjected to HPLC-SEC, calibrated HPAEC-PAD
      profiling (glucose units in relation to a malto-oligosaccharide ladder), and 1D
      (1)H NMR spectroscopy. For a more detailed analysis and support of the
      conclusions based on the initial analysis, the GOS products were separated into
      DP-pure subpools on Bio-Gel P-2 (MALDI-TOF-MS analysis), which were subjected to
      calibrated HPAEC-PAD profiling and (1)H NMR analysis. Unidentified peaks from
      different GOS products, not present in Vivinal GOS, were isolated for detailed
      structural characterization. In this way, the differences between the various GOS
      products in terms of DP distribution and type of glycosidic linkages were
      established. A total of 13 new GOS structures were characterized, adding
      structural-reporter-group signals and HPAEC-PAD based glucose unit G.U. values to
      the analytical toolbox. The newly characterized products enhance the quality of
      the database with GOS structures up to DP4. The combined data provide a firm
      basis for the rapid profiling of the GOS products of microbial beta-galactosidase
      enzymes.

PMID- 27035912
TI  - Posttraumatic Stress and Attentional Bias towards Cancer-Related Stimuli in
      Parents of Children Recently Diagnosed with Cancer.
AB  - OBJECTIVES: To investigate whether posttraumatic stress symptoms (PTSS) are
      related to attentional bias towards cancer-related stimuli among parents of
      children recently diagnosed with cancer. METHODS: Sixty-two parents completed
      questionnaires measuring PTSS, depression, and anxiety and the emotional Stroop
      task via the Internet. The emotional Stroop task included cancer-related words,
      cardiovascular disease-related words, and neutral words. RESULTS: Participants
      were split in two groups based on the median of PTSS: High-PTSS and Low-PTSS.
      There was a significant interaction between word-type and group and a planned
      contrast test of this interaction indicated that the High-PTSS group had longer
      response latencies on cancer-related words compared to the other word-type and
      group combinations. CONCLUSIONS: Findings suggest that PTSS are related to
      attentional bias towards cancer-related stimuli among parents of children
      recently diagnosed with cancer. Implications of this finding for the
      understanding of PTSS in this population, future research, and clinical practice
      are discussed.

PMID- 27035913
TI  - Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with
      Concomitant Decrease in TGF-beta and Increase in IL-6.
AB  - BACKGROUND: 50% of leprosy patients suffer from episodes of Type 1/ reversal
      reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead
      to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+
      regulatory T cells (Tregs) have been shown to play a major role in disease
      associated immunopathology and in stable leprosy as reported by us and others.
      The aim of our study was to analyze their role in leprosy reactions. METHODOLOGY
      AND PRINCIPLE FINDINGS: Quantitative reverse transcribed PCR (qPCR),
      flowcytometry and ELISA were used to respectively investigate gene expression,
      cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC
      cultures in patients with stable disease and those undergoing leprosy reactions.
      Both types of reactions are associated with significant increase of Th17 cells
      and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22
      as compared to matching stable forms of leprosy. Concurrently patients in
      reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-beta
      and increase in IL-6. Moreover, expression of many T cell markers, cytokines,
      chemokines and signaling factors were observed to be increased in RR as compared
      to ENL reaction patients. CONCLUSIONS: Patients with leprosy reactions show an
      imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity
      is associated withhigherTh17cell activity. The combined effect of reduced TGF
      beta and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or
      Treg cells in leprosy reactions as reported in the murine models and autoimmune
      diseases. The increase in Th17 cell associated cytokines may contribute to
      lesional inflammation.

PMID- 27035914
TI  - The Prognostic Value of Decreased LKB1 in Solid Tumors: A Meta-Analysis.
AB  - BACKGROUND: Liver kinase B1 (LKB1) is a protein kinase that regulates the growth,
      integrity and polarity of mammalian cells. Recent studies have reported the
      prognostic value of decreased LKB1 expression in different tumors. However, the
      results of these studies remain controversial. Therefore, this meta-analysis was
      performed to more accurately estimate the role of decreased LKB1 in the
      prognostication of human solid tumors. METHODS: A systematic literature search in
      the electronic databases PubMed, Embase, Web of Science and CNKI (updated to
      October 15, 2015) was performed to identify eligible studies. The overall
      survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and
      clinicopathological features data were collected from these studies. The hazard
      ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated and pooled with a random-effects models using Stata12.0 software.
      RESULTS: A total of 14 studies covering 1915 patients with solid tumors were
      included in this meta-analysis. Decreased LKB1 was associated with poorer OS in
      both the univariate (HR: 1.86, 95%CI: 1.42-2.42, P<0.001) and multivariate (HR:
      1.55, 95%CI: 1.09-2.21, P = 0.015) analyses. A subgroup analysis revealed that
      the associations between decreased LKB1 and poor OS were significant within the
      Asian region (HR 2.18, 95%CI: 1.66-2.86, P<0.001) and obvious for lung cancer
      (HR: 2.16, 95%CI: 1.47-3.18, P<0.001). However, the articles that involved
      analyses of both RFS and DFS numbered only 3, and no statistically significant
      correlations of decreased LKB1 with RFS or DFS were observed in this study.
      Additionally, the pooled odds ratios (ORs) indicated that decreased LKB1 was
      associated with larger tumor size (OR: 1.60, 95%CI: 1.09-2.36, P = 0.017), lymph
      node metastasis (OR: 2.41, 95%CI: 1.53-3.78, P<0.001) and a higher TNM stage (OR:
      3.35, 95%CI: 2.20-5.09, P<0.001). CONCLUSION: These results suggest that
      decreased LKB1 expression in patients with solid tumors might be related to poor
      prognosis and serve as a potential predictive marker of poor clinicopathological
      prognostic factors. Additional studies are required to verify the clinical
      utility of decreased LKB1 in solid tumors.

PMID- 27035915
TI  - Elaboration of the Visual Pathways from the Study of War-Related Cranial
      Injuries: The Period from the Russo-Japanese War to World War I.
AB  - As a result of the wars in the early 20th century, elaboration of the visual
      pathways was greatly facilitated by the meticulous study of visual defects in
      soldiers who had suffered focal injuries to the visual cortex. Using relatively
      crude techniques, often under difficult wartime circumstances, investigators
      successfully mapped key features of the visual pathways. Studies during the Russo
      Japanese War (1904-1905) by Tatsuji Inouye (1881-1976) and during World War I by
      Gordon Holmes (1876-1965), William Lister (1868-1944), and others produced
      increasingly refined retinotopic maps of the primary visual cortex, which were
      later supported and refined by studies during and after World War II. Studies by
      George Riddoch (1888-1947) during World War I also demonstrated that some
      patients could still perceive motion despite blindness caused by damage to their
      visual cortex and helped to establish the concept of functional partitioning of
      visual processes in the occipital cortex. 

PMID- 27035916
TI  - Knowledge and Perceptions about Clinical Trials and the Use of Biomedical
      Samples: Findings from a Qualitative Study in Rural Northern Ghana.
AB  - INTRODUCTION: Clinical trials conducted in sub-Saharan Africa have helped to
      address the prevalent health challenges. The knowledge about how communities
      perceive clinical trials is however only now evolving. This study was conducted
      among parents whose children participated in past clinical trials in northern
      Ghana to assess their knowledge and perceptions of clinical trials and the use of
      biomedical samples. METHOD: This was a qualitative study based on eighty in-depth
      interviews with parents. The participants were randomly selected from among
      parents whose children were enrolled in a clinical trial conducted in the Kassena
      Nankana districts between 2000 and 2003. The interviews were transcribed and
      coded into emergent themes using Nvivo 9 software. The thematic analysis
      framework was used to analyze the data. RESULTS: Study participants reported that
      clinical trials were carried out to determine the efficacy of drugs and to make
      sure that these drugs were suitable for human beings to use. The conduct of
      clinical trials was perceived to have helped to reduce the occurrence of diseases
      such as malaria, cerebrospinal meningitis and diarrhea. Quality of care was
      reported to be better in clinical trials than in the routine care. Parents
      indicated that participation in clinical trials positively influenced their
      health-seeking behavior. Apprehensions about blood draw and the use to which
      samples were put were expressed, with suspicion by a few participants that
      researchers sold blood samples. The issue of blood draw was most contentious.
      CONCLUSION: Parents perception about the conduct of clinical trials in the study
      districts is generally positive. However, misconceptions made about the use of
      blood samples in this study must be taken seriously and strategies found to
      improve transparency and greater community acceptability.

PMID- 27035917
TI  - Clinical Outcomes after Selective Fetal Reduction of Complicated Monochorionic
      Twins with Radiofrequency Ablation and Bipolar Cord Coagulation.
AB  - AIMS: To review pregnancy outcomes, complication rates and neonatal neural
      development of selective termination procedures for complicated monochorionic
      (MC) twins. METHODS: This was a retrospective review of the pregnancies that
      underwent selective reduction with radiofrequency ablation (RFA) and bipolar cord
      coagulation (BCC) in our institution. RESULTS: Forty-eight cases underwent
      selective reduction with BCC and the remaining 45 with RFA. Overall survival was
      not statistically different between the RFA and BCC groups (71.1 and 62.5%, p =
      0.379). With regard to the indications, the survival rates were not significantly
      different for twin to twin transfusion syndrome, twin reversed arterial
      perfusion, discordant anomalies and selective intrauterine growth restriction.
      Preterm premature rupture of membrane was not statistically different between the
      BCC and RFA groups (47.9 and 33.3%, p = 0.153). Five foetuses presented with
      abnormal middle cerebral artery-peak systolic velocity in the BCC group and 4 in
      the RFA group (p = 0.829). In the BCC group, neurological injury was detected in
      2 neonates, presenting with cerebral dysplasia on MR scanning. In the RFA group,
      intracranial haemorrhage Grade III was detected in one neonate with cranial
      ultrasound (p = 0.607). CONCLUSIONS: Overall survival and complication rates
      following selective reduction in complicated MC twin pregnancies is similar
      irrespective of whether the reduction was performed using RFA or BCC. Key
      Message: It seems that selective reduction in MC pregnancies with RFA does not
      carry a significant decrease in the overall survival and complication rates than
      the cases with BCC. According to our data, neurodevelopmental impairment of the
      co-twins is relatively seldom after selective reduction.

PMID- 27035919
TI  - Primary Urethral Plasmacytoma Treated with High-Dose-Rate Brachytherapy: A Case
      Report.
AB  - Primary urethral solitary plasmacytoma is a very rare variant of extramedullary
      plasmacytoma. In total, only 9 cases have been reported so far. Patients were
      treated either by surgery or by external radiation therapy. Here, we report on a
      22-year-old man, initially presenting with a palpable induration at the penis,
      intermittent dysuria and haematospermia, which was due to histologically
      confirmed solitary urethral kappa-restricted plasmacytoma. The patient
      subsequently underwent percutaneous and endo-urethral high-dose-rate
      brachytherapy with a total dose of 42 Gy applied in 14 fractions. Besides an
      uncomplicated urinary tract infection and hyperpigmentation of the penis, the
      patient tolerated the radiotherapy well and is still free of disease after 15
      months follow-up.

PMID- 27035918
TI  - Staphylococcus aureus Transcriptome Architecture: From Laboratory to Infection
      Mimicking Conditions.
AB  - Staphylococcus aureus is a major pathogen that colonizes about 20% of the human
      population. Intriguingly, this Gram-positive bacterium can survive and thrive
      under a wide range of different conditions, both inside and outside the human
      body. Here, we investigated the transcriptional adaptation of S. aureus HG001, a
      derivative of strain NCTC 8325, across experimental conditions ranging from
      optimal growth in vitro to intracellular growth in host cells. These data
      establish an extensive repertoire of transcription units and non-coding RNAs, a
      classification of 1412 promoters according to their dependence on the RNA
      polymerase sigma factors SigA or SigB, and allow identification of new potential
      targets for several known transcription factors. In particular, this study
      revealed a relatively low abundance of antisense RNAs in S. aureus, where they
      overlap only 6% of the coding genes, and only 19 antisense RNAs not co
      transcribed with other genes were found. Promoter analysis and comparison with
      Bacillus subtilis links the small number of antisense RNAs to a less profound
      impact of alternative sigma factors in S. aureus. Furthermore, we revealed that
      Rho-dependent transcription termination suppresses pervasive antisense
      transcription, presumably originating from abundant spurious transcription
      initiation in this A+T-rich genome, which would otherwise affect expression of
      the overlapped genes. In summary, our study provides genome-wide information on
      transcriptional regulation and non-coding RNAs in S. aureus as well as new
      insights into the biological function of Rho and the implications of spurious
      transcription in bacteria. 

PMID- 27035920
TI  - The Prevalence of Diabetes and Prediabetes in the Adult Population of Jeddah,
      Saudi Arabia--A Community-Based Survey.
AB  - BACKGROUND: Type 2 (T2DM) is believed to be common in Saudi Arabia, but data are
      limited. In this population survey, we determined the prevalence of T2DM and
      prediabetes. MATERIALS AND METHODS: A representative sample among residents aged
      >= 18 years of the city of Jeddah was obtained comprising both Saudi and non
      Saudi families (N = 1420). Data on dietary, clinical and socio-demographic
      characteristics were collected and anthropometric measurements taken. Fasting
      plasma glucose and glycated hemoglobin (HbA1c) were used to diagnose diabetes and
      prediabetes employing American Diabetes Association criteria. Multiple logistic
      regression analysis was used to identify factors associated with T2DM. RESULTS:
      Age and sex standardized prevalence of prediabetes was 9.0% (95% CI 7.5-10.5);
      9.4% (7.1-11.8) in men and 8.6% (6.6-10.6) in women. For DM it was 12.1% (10.7
      13.5); 12.9% (10.7-13.5) in men and 11.4% (9.5-13.3) in women. The prevalence
      based on World Population as standard was 18.3% for DM and 11.9% for prediabetes.
      The prevalence of DM and prediabetes increased with age. Of people aged >=50
      years 46% of men and 44% of women had DM. Prediabetes and DM were associated with
      various measures of adiposity. DM was also associated with and family history of
      dyslipidemia in women, cardiovascular disease in men, and with hypertension,
      dyslipidemia and family history of diabetes in both sexes. DISCUSSION: Age was
      the strongest predictor of DM and prediabetes followed by obesity. Of people aged
      50 years or over almost half had DM and another 10-15% had prediabetes leaving
      only a small proportion of people in this age group with normoglycemia. Since we
      did not use an oral glucose tolerance test the true prevalence of DM and
      prediabetes is thus likely to be even higher than reported here. These results
      demonstrate the urgent need to develop primary prevention strategies for type 2
      diabetes in Saudi Arabia.

PMID- 27035921
TI  - Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem
      Cells.
AB  - BACKGROUND/AIMS: Embryonic developmental studies under microgravity conditions in
      space are very limited. To study the effects of altered gravity on the embryonic
      development processes we established an in vitro methodology allowing
      differentiation of mouse embryonic stem cells (mESCs) under simulated
      microgravity within a fast-rotating clinostat (clinorotation) and capture of
      microarray-based gene signatures. METHODS: The differentiating mESCs were
      cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were
      used to capture genes that are deregulated by simulated microgravity and their
      impact on developmental biological processes. RESULTS: The data analysis
      demonstrated that differentiation of mESCs in pipettes for 3 days resultet to
      early germ layer differentiation and then to the different somatic cell types
      after further 7 days of differentiation in the Petri dishes. Clinorotation
      influences differentiation as well as non-differentiation related biological
      processes like cytoskeleton related 19 genes were modulated. Notably, simulated
      microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and
      Dll1 are involved in heart morphogenesis as an acute response on day 3. If the
      stem cells were further cultivated under normal gravity conditions (1 g) after
      clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2,
      Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well
      with a decreasing beating activity of the 10-days old embryoid bodies (EBs).
      Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions
      were modulated by simulated microgravity and by real microgravity in various
      reported studies. Simulated microgravity also deregulated genes belonging to the
      MAP kinase and focal dhesion signal transduction pathways. CONCLUSION: One of the
      most prominent biological processes affected by simulated microgravity was the
      process of cardiomyogenesis. The most significant simulated microgravity-affected
      genes, signal transduction pathways, and biological processes which are relevant
      for mESCs differentiation have been identified and discussed below.

PMID- 27035922
TI  - Nostalgia in the Army (17th-19th Centuries).
AB  - People died from nostalgia in the army in the 17th-19th centuries. The term
      'nostalgia', created by the doctor Johannes Hofer (1669-1752), from Mulhouse,
      came from the Germanic Heimweh, or 'homesickness'. It affected the young people
      enrolled in the army, such as Swiss mercenaries. Longing for their native land,
      they were consumed by an ongoing desire to return home. If it was impossible to
      do so, they sank into 'a sadness accompanied with insomnia, anorexia and other
      unpleasant symptoms' that could lead to death. Nostalgia became classified as a
      disease during the last quarter of the 18th century and ravaged the French army
      during the Revolution and the Napoleonic wars. However, as soon as the wars
      ended, it ceased to exist in the army (except the colonial army). It was removed
      from the nosology in the first half of the 19th century. Rapidly explained as an
      example of a misdiagnosis or a confusion between 'connection and cause',
      nostalgia needs to be assessed in regard to the medical debate between
      'alienists' and 'organicists'. Creating much concern, nostalgia needs to be
      considered in the historical context of a society destabilized by modernity, with
      some individuals uprooted by the sudden transition from civil society to military
      life. It raises questions about the role that the army played in the creation of
      the French national union. Nostalgia may have also covered psychic traumatisms
      later designated as combat fatigue, war neurosis, or post-traumatic stress
      disorder. 

PMID- 27035923
TI  - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) in paired maternal and
      neonatal samples from South China: Placental transfer and potential risks.
AB  - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are attracting more and
      more attention for the neurodevelopment toxicity effects. We evaluated the
      concentrations of 15 individual OH-PBDEs and 3 bromophenol (BRP) congeners in 30
      mother-newborn paired placenta, breast milk, fetal cord blood, and neonatal urine
      samples collected from South China. The geometric mean (GM) concentrations of ?OH
      PBDEs were 37.6, 61.3, and 76.8pgg(-1) ww in placenta, breast milk, and cord
      blood, respectively. The GM concentrations of ?BRPs were 47.6, 119, and 30.2pgg(
      1) ww in placenta, breast milk, and cord blood, respectively. The GM
      concentrations of ?OH-PBDEs and ?BRPs in neonatal urine were 72.0 and 79.8pgml(
      1), respectively. Of the 15 OH-PBDE congeners analyzed, the three most frequently
      detected congeners were 2'-OH-BDE-68 (72.1%), 6-OH-BDE-47 (67.6%), and 2'-OH-BDE
      28 (65.8%). The estimated daily intake (EDI) of OH-PBDEs for the breast-fed
      infants was 9.31+/-4.00ngkg(-1) bw day. The accumulation of OH-PBDEs in newborns
      was much lower than the estimated lowest observed-effect concentration (LOEC) of
      neurotoxicity. The present study provided the first systematic fundamental data
      that exposure to OH-PBDEs for newborn and their mothers in South China.

PMID- 27035924
TI  - The intersection of aggregate-level lead exposure and crime.
AB  - CONTEXT: Childhood lead exposure has been associated with criminal behavior later
      in life. The current study aimed to analyze the association between elevated
      blood lead levels (n=59,645) and crime occurrence (n=90,433) across census tracts
      within St. Louis, Missouri. DESIGN: Longitudinal ecological study. SETTING: Saint
      Louis, Missouri. EXPOSURE MEASURE: Blood lead levels. MAIN OUTCOME MEASURE:
      Violent, Non-violent, and total crime at the census tract level. RESULTS: Spatial
      statistical models were used to account for the spatial autocorrelation of the
      data. Greater lead exposure at the census-tract level was associated with
      increased violent, non-violent, and total crime. In addition, we examined whether
      non-additive effects existed in the data by testing for an interaction between
      lead exposure and concentrated disadvantage. Some evidence of a negative
      interaction emerged, however, it failed to reach traditional levels of
      statistical significance (supplementary models, however, revealed a similar
      negative interaction that was significant). CONCLUSIONS: More precise
      measurements of lead exposure in the aggregate, produced additional evidence that
      lead is a potent predictor of criminal outcomes.

PMID- 27035925
TI  - Dynamically-downscaled probabilistic projections of precipitation changes: A
      Canadian case study.
AB  - In this study, plausible changes in annual and seasonal precipitation over
      Ontario, Canada in response to global warming are investigated through a regional
      climate modeling approach. A high-resolution regional climate model ensemble
      based upon the Providing REgional Climates for Impacts Studies (PRECIS) model is
      developed to help explore the possible outcomes of future climate. A Bayesian
      hierarchical model is then employed to quantify the uncertainties involved in the
      modeling results and obtain probabilistic projections of precipitation changes at
      grid point scales. The results show that the projected changes in annual
      precipitation exhibit a certain degree of spatial variability with the median
      changes mostly bounded by 0% and 20%, implying that the annual precipitation over
      Ontario is more likely to increase in the context of global warming.
      Specifically, the mean changes in annual precipitation for 2030s and 2050s would
      be ~7.5%, while the annual precipitation for 2080s is likely to increase by an
      average of ~12.5%. By contrast, the spatial variability of seasonal precipitation
      changes is more significant, especially for the changes in spring precipitation
      which may vary from -40% in south and 50% in north. It is reported that there
      would be a continuous increasing trend in winter, spring, and autumn
      precipitation from 2030s to 2080s by 5-30%, but summer precipitation is likely to
      decrease by 5% or even higher to the end of this century. Furthermore, our
      results suggest that the larger the biases in historical simulations, the more
      uncertain the future projections will be.

PMID- 27035926
TI  - Multidimensional operando analysis of macroscopic structure evolution in lithium
      sulfur cells by X-ray radiography.
AB  - Lithium sulfur cells are the most promising candidate for the post lithium-ion
      battery era. Their major drawback is rapid capacity fading attributed to the
      complex electrochemical processes during charge and discharge which are not known
      precisely. Here we present for the first time a multidimensional operando
      measurement by combining X-ray radiography with impedance spectroscopy while
      galvanostatically charging and discharging a lithium sulfur cell. The formation
      of macroscopic sulfur crystals at the end of charge can be seen directly by X-ray
      radiography. These crystals can be assigned to stable alpha-sulfur (rhombic) and
      metastable beta-sulfur (monoclinic) by their characteristic crystal habit. These
      crystal structures with a length of more than 1 mm form and dissolve rapidly
      during cycling. Their appearance is accompanied by characteristic signals in
      impedance spectroscopy. Macroscopic crystals of Li2S cannot be observed in full
      agreement with earlier studies by operando X-ray diffraction. In addition, X-ray
      radiography reveals non-wetted areas on the carbon cathode. These regions grow
      during discharge and are reduced during charge. The area of these
      electrochemically inactive spots is inversely proportional to discharge capacity.

PMID- 27035927
TI  - Reply to "Letter to Editor: Main-duct Intraductal Papillary Mucinous Neoplasm:
      High Cancer Risk in Duct Diameter of 5 to 9 mm" by Marco Del Chiaro and Richard
      D. Schulick.

PMID- 27035928
TI  - A robust biomarker of differential correlations improves the diagnosis of
      cytologically indeterminate thyroid cancers.
AB  - The fine-needle aspiration of thyroid nodules and subsequent cytological analysis
      is unable to determine the diagnosis in 15 to 30% of thyroid cancer cases;
      patients with indeterminate cytological results undergo diagnostic surgery which
      is potentially unnecessary. Current gene expression biomarkers based on well
      determined cytology are complex and their accuracy is inconsistent across public
      datasets. In the present study, we identified a robust biomarker using the
      differences in gene expression values specifically from cytologically
      indeterminate thyroid tumors and a powerful multivariate search tool coupled with
      a nearest centroid classifier. The biomarker is based on differences in the
      expression of the following genes: CCND1, CLDN16, CPE, LRP1B, MAGI3, MAPK6,
      MATN2, MPPED2, PFKFB2, PTPRE, PYGL, SEMA3D, SERGEF, SLC4A4 and TIMP1. This 15
      gene biomarker exhibited superior accuracy independently of the cytology in six
      datasets, including The Cancer Genome Atlas (TCGA) thyroid dataset. In addition,
      this biomarker exhibited differences in the correlation coefficients between
      benign and malignant samples that indicate its discriminatory power, and these 15
      genes have been previously related to cancer in the literature. Thus, this 15
      gene biomarker provides advantages in clinical practice for the effective
      diagnosis of thyroid cancer.

PMID- 27035929
TI  - Physical activity levels and quality of life relate to collagen turnover and
      inflammation changes after running.
AB  - The purpose of this study was to determine whether an association existed between
      self-reported symptom and function scores and tissue turnover or inflammatory
      biomarker changes after a running bout among individuals with and without an
      acute knee-injury history. A pre-test/post-test prospective cohort study design
      (Level II) of 22 participants was conducted. Eleven physically active individuals
      with a history of anterior cruciate ligament surgery and/or meniscus surgery
      within 4 years of study participation were matched to 11 healthy control
      participants. All participants completed self-reported outcome measures (Knee
      Osteoarthritis Outcomes Score and Tegner activity level) assessing knee symptoms
      and functional levels prior to the run. Blood samples were taken both pre- and
      post-30-minute run at a prescribed pace on a treadmill to determine serum
      biomarker concentration changes. Tegner activity levels were inversely related to
      type II collagen/type II collagen synthesis marker ratio biomarker changes after
      the run (r = -0.45, p = 0.01). Quality-of-life scores pre-exercise were inversely
      related to interleukin-1beta changes after the run (r = -0.50, p = 0.02). No
      other correlation coefficients were statistically significant (r = -0.39 to
      0.36). Ultimately, individuals with lower activity and quality-of-life scores
      experienced greater increases in collagen turnover and inflammation after a
      running bout, respectively. A gradual increase in activity (e.g., frequency,
      duration, intensity) may be warranted in this group prior to returning to
      activities that involve running. (c) 2016 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 35:612-617, 2017.

PMID- 27035932
TI  - Science and Culture: Dancing with Pythagoras.

PMID- 27035930
TI  - Opinion: A new paradigm for regulating genetically engineered animals that are
      used as food.

PMID- 27035933
TI  - Inner Workings: Exploring ancient storms in marshes, corals, and caves.

PMID- 27035935
TI  - Modulation of nitrogen vacancy charge state and fluorescence in nanodiamonds
      using electrochemical potential.
AB  - The negatively charged nitrogen vacancy (NV(-)) center in diamond has attracted
      strong interest for a wide range of sensing and quantum information processing
      applications. To this end, recent work has focused on controlling the NV charge
      state, whose stability strongly depends on its electrostatic environment. Here,
      we demonstrate that the charge state and fluorescence dynamics of single NV
      centers in nanodiamonds with different surface terminations can be controlled by
      an externally applied potential difference in an electrochemical cell. The
      voltage dependence of the NV charge state can be used to stabilize the NV(-)
      state for spin-based sensing protocols and provides a method of charge state
      dependent fluorescence sensing of electrochemical potentials. We detect clear NV
      fluorescence modulation for voltage changes down to 100 mV, with a single NV and
      down to 20 mV with multiple NV centers in a wide-field imaging mode. These
      results suggest that NV centers in nanodiamonds could enable parallel optical
      detection of biologically relevant electrochemical potentials. 

PMID- 27035936
TI  - Discrete gene replication events drive coupling between the cell cycle and
      circadian clocks.
AB  - Many organisms possess both a cell cycle to control DNA replication and a
      circadian clock to anticipate changes between day and night. In some cases, these
      two rhythmic systems are known to be coupled by specific, cross-regulatory
      interactions. Here, we use mathematical modeling to show that, additionally, the
      cell cycle generically influences circadian clocks in a nonspecific fashion: The
      regular, discrete jumps in gene-copy number arising from DNA replication during
      the cell cycle cause a periodic driving of the circadian clock, which can
      dramatically alter its behavior and impair its function. A clock built on
      negative transcriptional feedback either phase-locks to the cell cycle, so that
      the clock period tracks the cell division time, or exhibits erratic behavior. We
      argue that the cyanobacterium Synechococcus elongatus has evolved two features
      that protect its clock from such disturbances, both of which are needed to fully
      insulate it from the cell cycle and give it its observed robustness: a
      phosphorylation-based protein modification oscillator, together with its
      accompanying push-pull read-out circuit that responds primarily to the ratios of
      different phosphoform concentrations, makes the clock less susceptible to
      perturbations in protein synthesis; the presence of multiple, asynchronously
      replicating copies of the same chromosome diminishes the effect of replicating
      any single copy of a gene. 

PMID- 27035937
TI  - Dominant, open nonverbal displays are attractive at zero-acquaintance.
AB  - Across two field studies of romantic attraction, we demonstrate that postural
      expansiveness makes humans more romantically appealing. In a field study (n = 144
      speed-dates), we coded nonverbal behaviors associated with liking, love, and
      dominance. Postural expansiveness-expanding the body in physical space-was most
      predictive of attraction, with each one-unit increase in coded behavior from the
      video recordings nearly doubling a person's odds of getting a "yes" response from
      one's speed-dating partner. In a subsequent field experiment (n = 3,000), we
      tested the causality of postural expansion (vs. contraction) on attraction using
      a popular Global Positioning System-based online-dating application. Mate-seekers
      rapidly flipped through photographs of potential sexual/date partners, selecting
      those they desired to meet for a date. Mate-seekers were significantly more
      likely to select partners displaying an expansive (vs. contractive) nonverbal
      posture. Mediation analyses demonstrate one plausible mechanism through which
      expansiveness is appealing: Expansiveness makes the dating candidate appear more
      dominant. In a dating world in which success sometimes is determined by a split
      second decision rendered after a brief interaction or exposure to a static
      photograph, single persons have very little time to make a good impression. Our
      research suggests that a nonverbal dominance display increases a person's chances
      of being selected as a potential mate. 

PMID- 27035938
TI  - GOLDEN 2-LIKE transcription factors for chloroplast development affect ozone
      tolerance through the regulation of stomatal movement.
AB  - Stomatal movements regulate gas exchange, thus directly affecting the efficiency
      of photosynthesis and the sensitivity of plants to air pollutants such as ozone.
      The GARP family transcription factors GOLDEN 2-LIKE1 (GLK1) and GLK2 have known
      functions in chloroplast development. Here, we show that Arabidopsis thaliana (A.
      thaliana) plants expressing the chimeric repressors for GLK1 and -2 (GLK1/2-SRDX)
      exhibited a closed-stomata phenotype and strong tolerance to ozone. By contrast,
      plants that overexpress GLK1/2 exhibited an open-stomata phenotype and higher
      sensitivity to ozone. The plants expressing GLK1-SRDX had reduced expression of
      the genes for inwardly rectifying K(+) (K(+) in) channels and reduced K(+) in
      channel activity. Abscisic acid treatment did not affect the stomatal phenotype
      of 35S:GLK1/2-SRDX plants or the transcriptional activity for K(+) in channel
      gene, indicating that GLK1/2 act independently of abscisic acid signaling. Our
      results indicate that GLK1/2 positively regulate the expression of genes for K(+)
      in channels and promote stomatal opening. Because the chimeric GLK1-SRDX
      repressor driven by a guard cell-specific promoter induced a closed-stomata
      phenotype without affecting chloroplast development in mesophyll cells,
      modulating GLK1/2 activity may provide an effective tool to control stomatal
      movements and thus to confer resistance to air pollutants. 

PMID- 27035939
TI  - Major spliceosome defects cause male infertility and are associated with
      nonobstructive azoospermia in humans.
AB  - Processing of pre-mRNA into mRNA is an important regulatory mechanism in
      eukaryotes that is mediated by the spliceosome, a huge and dynamic
      ribonucleoprotein complex. Splicing defects are implicated in a spectrum of human
      disease, but the underlying mechanistic links remain largely unresolved. Using a
      genome-wide association approach, we have recently identified single nucleotide
      polymorphisms in humans that associate with nonobstructive azoospermia (NOA), a
      common cause of male infertility. Here, using genetic manipulation of
      corresponding candidate loci in Drosophila, we show that the spliceosome
      component SNRPA1/U2A is essential for male fertility. Loss of U2A in germ cells
      of the Drosophila testis does not affect germline stem cells, but does result in
      the accumulation of mitotic spermatogonia that fail to differentiate into
      spermatocytes and mature sperm. Lack of U2A causes insufficient splicing of mRNAs
      required for the transition of germ cells from proliferation to differentiation.
      We show that germ cell-specific disruption of other components of the major
      spliceosome manifests with the same phenotype, demonstrating that mRNA processing
      is required for the differentiation of spermatogonia. This requirement is
      conserved, and expression of human SNRPA1 fully restores spermatogenesis in U2A
      mutant flies. We further report that several missense mutations in human SNRPA1
      that inhibit the assembly of the major spliceosome dominantly disrupt
      spermatogonial differentiation in Drosophila. Collectively, our findings uncover
      a conserved and specific requirement for the major spliceosome during the
      transition from spermatogonial proliferation to differentiation in the male
      testis, suggesting that spliceosome defects affecting the differentiation of
      human spermatogonia contribute to NOA. 

PMID- 27035940
TI  - Defects in lysosomal maturation facilitate the activation of innate sensors in
      systemic lupus erythematosus.
AB  - Defects in clearing apoptotic debris disrupt tissue and immunological
      homeostasis, leading to autoimmune and inflammatory diseases. Herein, we report
      that macrophages from lupus-prone MRL/lpr mice have impaired lysosomal
      maturation, resulting in heightened ROS production and attenuated lysosomal
      acidification. Impaired lysosomal maturation diminishes the ability of lysosomes
      to degrade apoptotic debris contained within IgG-immune complexes (IgG-ICs) and
      promotes recycling and the accumulation of nuclear self-antigens at the membrane
      72 h after internalization. Diminished degradation of IgG-ICs prolongs the
      intracellular residency of nucleic acids, leading to the activation of Toll-like
      receptors. It also promotes phagosomal membrane permeabilization, allowing dsDNA
      and IgG to leak into the cytosol and activate AIM2 and TRIM21. Collectively,
      these events promote the accumulation of nuclear antigens and activate innate
      sensors that drive IFNalpha production and heightened cell death. These data
      identify a previously unidentified defect in lysosomal maturation that provides a
      mechanism for the chronic activation of intracellular innate sensors in systemic
      lupus erythematosus. 

PMID- 27035941
TI  - Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic
      presynaptic and GABAergic postsynaptic structures.
AB  - Midbrain dopamine neurons project densely to the striatum and form so-called
      dopamine synapses on medium spiny neurons (MSNs), principal neurons in the
      striatum. Because dopamine receptors are widely expressed away from dopamine
      synapses, it remains unclear how dopamine synapses are involved in dopaminergic
      transmission. Here we demonstrate that dopamine synapses are contacts formed
      between dopaminergic presynaptic and GABAergic postsynaptic structures. The
      presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine
      transporter-2, and plasmalemmal dopamine transporter, which are essential for
      dopamine synthesis, vesicular filling, and recycling, but was below the detection
      threshold for molecules involving GABA synthesis and vesicular filling or for
      GABA itself. In contrast, the postsynaptic structure of dopamine synapses
      expressed GABAergic molecules, including postsynaptic adhesion molecule
      neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor
      alpha1, without any specific clustering of dopamine receptors. Of these,
      neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine
      neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown
      in the striatum, a significant decrease of dopamine synapses coupled with a
      reciprocal increase of GABAergic synapses was observed on MSN dendrites. This
      finding suggests that neuroligin-2 controls striatal synapse formation by giving
      competitive advantage to heterologous dopamine synapses over conventional
      GABAergic synapses. Considering that MSN dendrites are preferential targets of
      dopamine synapses and express high levels of dopamine receptors, dopamine synapse
      formation may serve to increase the specificity and potency of dopaminergic
      modulation of striatal outputs by anchoring dopamine release sites to dopamine
      sensing targets. 

PMID- 27035942
TI  - Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide
      excision repair complex.
AB  - DNA damage repair starts with the recognition of damaged sites from predominantly
      normal DNA. In eukaryotes, diverse DNA lesions from environmental sources are
      recognized by the xeroderma pigmentosum C (XPC) nucleotide excision repair
      complex. Studies of Rad4 (radiation-sensitive 4; yeast XPC ortholog) showed that
      Rad4 "opens" up damaged DNA by inserting a beta-hairpin into the duplex and
      flipping out two damage-containing nucleotide pairs. However, this DNA lesion
      "opening" is slow (~5-10 ms) compared with typical submillisecond residence times
      per base pair site reported for various DNA-binding proteins during 1D diffusion
      on DNA. To address the mystery as to how Rad4 pauses to recognize lesions during
      diffusional search, we examine conformational dynamics along the lesion
      recognition trajectory using temperature-jump spectroscopy. Besides identifying
      the ~10-ms step as the rate-limiting bottleneck towards opening specific DNA
      site, we uncover an earlier ~100- to 500-MUs step that we assign to nonspecific
      deformation (unwinding/"twisting") of DNA by Rad4. The beta-hairpin is not
      required to unwind or to overcome the bottleneck but is essential for full
      nucleotide-flipping. We propose that Rad4 recognizes lesions in a step-wise
      "twist-open" mechanism, in which preliminary twisting represents Rad4
      interconverting between search and interrogation modes. Through such
      conformational switches compatible with rapid diffusion on DNA, Rad4 may stall
      preferentially at a lesion site, offering time to open DNA. This study represents
      the first direct observation, to our knowledge, of dynamical DNA distortions
      during search/interrogation beyond base pair breathing. Submillisecond
      interrogation with preferential stalling at cognate sites may be common to
      various DNA-binding proteins. 

PMID- 27035943
TI  - Conditional vulnerability of plant diversity to atmospheric nitrogen deposition
      across the United States.
AB  - Atmospheric nitrogen (N) deposition has been shown to decrease plant species
      richness along regional deposition gradients in Europe and in experimental
      manipulations. However, the general response of species richness to N deposition
      across different vegetation types, soil conditions, and climates remains largely
      unknown even though responses may be contingent on these environmental factors.
      We assessed the effect of N deposition on herbaceous richness for 15,136 forest,
      woodland, shrubland, and grassland sites across the continental United States, to
      address how edaphic and climatic conditions altered vulnerability to this
      stressor. In our dataset, with N deposition ranging from 1 to 19 kg N?ha(-1)?y(
      1), we found a unimodal relationship; richness increased at low deposition levels
      and decreased above 8.7 and 13.4 kg N?ha(-1)?y(-1) in open and closed-canopy
      vegetation, respectively. N deposition exceeded critical loads for loss of plant
      species richness in 24% of 15,136 sites examined nationwide. There were negative
      relationships between species richness and N deposition in 36% of 44 community
      gradients. Vulnerability to N deposition was consistently higher in more acidic
      soils whereas the moderating roles of temperature and precipitation varied across
      scales. We demonstrate here that negative relationships between N deposition and
      species richness are common, albeit not universal, and that fine-scale processes
      can moderate vegetation responses to N deposition. Our results highlight the
      importance of contingent factors when estimating ecosystem vulnerability to N
      deposition and suggest that N deposition is affecting species richness in
      forested and nonforested systems across much of the continental United States. 

PMID- 27035944
TI  - Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock
      copolypeptoid tiles.
AB  - The folding and assembly of sequence-defined polymers into precisely ordered
      nanostructures promises a class of well-defined biomimetic architectures with
      specific function. Amphiphilic diblock copolymers are known to self-assemble in
      water to form a variety of nanostructured morphologies including spheres, disks,
      cylinders, and vesicles. In all of these cases, the predominant driving force for
      assembly is the formation of a hydrophobic core that excludes water, whereas the
      hydrophilic blocks are solvated and extend into the aqueous phase. However, such
      polymer systems typically have broad molar mass distributions and lack the purity
      and sequence-defined structure often associated with biologically derived
      polymers. Here, we demonstrate that purified, monodisperse amphiphilic diblock
      copolypeptoids, with chemically distinct domains that are congruent in size and
      shape, can behave like molecular tile units that spontaneously assemble into
      hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous
      crystalline rings, and are held together primarily by side-chain van der Waals
      interactions. The peptoid nanotubes form without a central hydrophobic core,
      chirality, a hydrogen bond network, and electrostatic or pi-pi interactions.
      These results demonstrate the remarkable structure-directing influence of n
      alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this
      work suggests that flexible, low-molecular-weight sequence-defined polymers can
      serve as molecular tile units that can assemble into precision supramolecular
      architectures. 

PMID- 27035945
TI  - Horizontally acquired genes in early-diverging pathogenic fungi enable the use of
      host nucleosides and nucleotides.
AB  - Horizontal gene transfer (HGT) among bacteria, archaea, and viruses is
      widespread, but the extent of transfers from these lineages into eukaryotic
      organisms is contentious. Here we systematically identify hundreds of genes that
      were likely acquired horizontally from a variety of sources by the early
      diverging fungal phyla Microsporidia and Cryptomycota. Interestingly, the
      Microsporidia have acquired via HGT several genes involved in nucleic acid
      synthesis and salvage, such as those encoding thymidine kinase (TK), cytidylate
      kinase, and purine nucleotide phosphorylase. We show that these HGT-derived
      nucleic acid synthesis genes tend to function at the interface between the
      metabolic networks of the host and pathogen. Thus, these genes likely play vital
      roles in diversifying the useable nucleic acid components available to the
      intracellular parasite, often through the direct capture of resources from the
      host. Using an in vivo viability assay, we also demonstrate that one of these
      genes, TK, encodes an enzyme that is capable of activating known prodrugs to
      their active form, which suggests a possible treatment route for
      microsporidiosis. We further argue that interfacial genes with well-understood
      activities, especially those horizontally transferred from bacteria or viruses,
      could provide medical treatments for microsporidian infections. 

PMID- 27035946
TI  - Discovering governing equations from data by sparse identification of nonlinear
      dynamical systems.
AB  - Extracting governing equations from data is a central challenge in many diverse
      areas of science and engineering. Data are abundant whereas models often remain
      elusive, as in climate science, neuroscience, ecology, finance, and epidemiology,
      to name only a few examples. In this work, we combine sparsity-promoting
      techniques and machine learning with nonlinear dynamical systems to discover
      governing equations from noisy measurement data. The only assumption about the
      structure of the model is that there are only a few important terms that govern
      the dynamics, so that the equations are sparse in the space of possible
      functions; this assumption holds for many physical systems in an appropriate
      basis. In particular, we use sparse regression to determine the fewest terms in
      the dynamic governing equations required to accurately represent the data. This
      results in parsimonious models that balance accuracy with model complexity to
      avoid overfitting. We demonstrate the algorithm on a wide range of problems, from
      simple canonical systems, including linear and nonlinear oscillators and the
      chaotic Lorenz system, to the fluid vortex shedding behind an obstacle. The fluid
      example illustrates the ability of this method to discover the underlying
      dynamics of a system that took experts in the community nearly 30 years to
      resolve. We also show that this method generalizes to parameterized systems and
      systems that are time-varying or have external forcing. 

PMID- 27035947
TI  - Testing theories of financial decision making.
AB  - We describe the observable content of some of the most widely used models of
      decision under uncertainty: models of translation invariant preferences. In
      particular, we characterize the models of variational, maxmin, constant absolute
      risk aversion, and constant relative risk aversion utilities. In each case we
      present a revealed preference axiom that is satisfied by a dataset if and only if
      the dataset is consistent with the corresponding utility representation. We test
      our axioms using data from an experiment on financial decisions. 

PMID- 27035948
TI  - Transmission dynamics of Ebola virus disease and intervention effectiveness in
      Sierra Leone.
AB  - Sierra Leone is the most severely affected country by an unprecedented outbreak
      of Ebola virus disease (EVD) in West Africa. Although successfully contained, the
      transmission dynamics of EVD and the impact of interventions in the country
      remain unclear. We established a database of confirmed and suspected EVD cases
      from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal
      distribution of cases at the chiefdom level. A Poisson transmission model
      revealed that the transmissibility at the chiefdom level, estimated as the
      average number of secondary infections caused by a patient per week, was reduced
      by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the
      strategic plan of the United Nations Mission for Emergency Ebola Response was
      initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when
      100% case isolation and safe burials were essentially achieved, both compared
      with before October 2014. Population density, proximity to Ebola treatment
      centers, cropland coverage, and atmospheric temperature were associated with EVD
      transmission. The household secondary attack rate (SAR) was estimated to be 0.059
      (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by
      82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case
      isolation and safe burials had been conducted. This study provides a complete
      overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra
      Leone at both chiefdom and household levels. The interventions implemented in
      Sierra Leone seem effective in containing the epidemic, particularly in
      interrupting household transmission. 

PMID- 27035950
TI  - Coastal landforms and accumulation of mangrove peat increase carbon sequestration
      and storage.
AB  - Given their relatively small area, mangroves and their organic sediments are of
      disproportionate importance to global carbon sequestration and carbon storage.
      Peat deposition and preservation allows some mangroves to accrete vertically and
      keep pace with sea-level rise by growing on their own root remains. In this study
      we show that mangroves in desert inlets in the coasts of the Baja California have
      been accumulating root peat for nearly 2,000 y and harbor a belowground carbon
      content of 900-34,00 Mg C/ha, with an average value of 1,130 (+/- 128) Mg C/ha,
      and a belowground carbon accumulation similar to that found under some of the
      tallest tropical mangroves in the Mexican Pacific coast. The depth-age curve for
      the mangrove sediments of Baja California indicates that sea level in the
      peninsula has been rising at a mean rate of 0.70 mm/y (+/- 0.07) during the last
      17 centuries, a value similar to the rates of sea-level rise estimated for the
      Caribbean during a comparable period. By accreting on their own accumulated peat,
      these desert mangroves store large amounts of carbon in their sediments. We
      estimate that mangroves and halophyte scrubs in Mexico's arid northwest, with
      less than 1% of the terrestrial area, store in their belowground sediments around
      28% of the total belowground carbon pool of the whole region. 

PMID- 27035949
TI  - Differential and enhanced response to climate forcing in diarrheal disease due to
      rotavirus across a megacity of the developing world.
AB  - The role of climate forcing in the population dynamics of infectious diseases has
      typically been revealed via retrospective analyses of incidence records
      aggregated across space and, in particular, over whole cities. Here, we focus on
      the transmission dynamics of rotavirus, the main diarrheal disease in infants and
      young children, within the megacity of Dhaka, Bangladesh. We identify two zones,
      the densely urbanized core and the more rural periphery, that respond
      differentially to flooding. Moreover, disease seasonality differs substantially
      between these regions, spanning variation comparable to the variation from
      tropical to temperate regions. By combining process-based models with an
      extensive disease surveillance record, we show that the response to climate
      forcing is mainly seasonal in the core, where a more endemic transmission
      resulting from an asymptomatic reservoir facilitates the response to the
      monsoons. The force of infection in this monsoon peak can be an order of
      magnitude larger than the force of infection in the more epidemic periphery,
      which exhibits little or no postmonsoon outbreak in a pattern typical of nearby
      rural areas. A typically smaller peak during the monsoon season nevertheless
      shows sensitivity to interannual variability in flooding. High human density in
      the core is one explanation for enhanced transmission during troughs and an
      associated seasonal monsoon response in this diarrheal disease, which unlike
      cholera, has not been widely viewed as climate-sensitive. Spatial demographic,
      socioeconomic, and environmental heterogeneity can create reservoirs of infection
      and enhance the sensitivity of disease systems to climate forcing, especially in
      the populated cities of the developing world. 

PMID- 27035951
TI  - Hunted gazelles evidence cooling, but not drying, during the Younger Dryas in the
      southern Levant.
AB  - The climatic downturn known globally as the Younger Dryas (YD; ~12,900-11,500 BP)
      has frequently been cited as a prime mover of agricultural origins and has thus
      inspired enthusiastic debate over its local impact. This study presents seasonal
      climatic data from the southern Levant obtained from the sequential sampling of
      gazelle tooth carbonates from the Early and Late Natufian archaeological sites of
      Hayonim and Hilazon Tachtit Caves (western Galilee, Israel). Our results
      challenge the entrenched model that assumes that warm temperatures and high
      precipitation are synonymous with climatic amelioration and cold and wet
      conditions are combined in climatic downturns. Enamel carbon isotope values from
      teeth of human-hunted gazelle dating before and during the YD provide a proxy
      measure for water availability during plant growth. They reveal that although the
      YD was cooler, it was not drier than the preceding Bolling-Allerod. In addition,
      the magnitude of the seasonal curve constructed from oxygen isotopes is
      significantly dampened during the YD, indicating that cooling was most pronounced
      in the growing season. Cool temperatures likely affected the productivity of
      staple wild cereal resources. We hypothesize that human groups responded by
      shifting settlement strategies-increasing population mobility and perhaps moving
      to the warmer Jordan Valley where wild cereals were more productive and stable. 

PMID- 27035952
TI  - Oral activity of a nature-derived cyclic peptide for the treatment of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is the most common autoimmune disease affecting the
      central nervous system. It is characterized by auto-reactive T cells that induce
      demyelination and neuronal degradation. Treatment options are still limited and
      several MS medications need to be administered by parenteral application but are
      modestly effective. Oral active drugs such as fingolimod have been weighed down
      by safety concerns. Consequently, there is a demand for novel, especially orally
      active therapeutics. Nature offers an abundance of compounds for drug discovery.
      Recently, the circular plant peptide kalata B1 was shown to silence T-cell
      proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising
      effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1
      using the MS mouse model experimental autoimmune encephalomyelitis (EAE).
      Treatment of mice with the cyclotide resulted in a significant delay and
      diminished symptoms of EAE by oral administration. Cyclotide application
      substantially impeded disease progression and did not exhibit adverse effects.
      Inhibition of lymphocyte proliferation and the reduction of proinflammatory
      cytokines, in particular IL-2, distinguish the cyclotide from other marketed
      drugs. Considering their stable structural topology and oral activity, cyclotides
      are candidates as peptide therapeutics for pharmaceutical drug development for
      treatment of T-cell-mediated disorders. 

PMID- 27035953
TI  - Global fishery prospects under contrasting management regimes.
AB  - Data from 4,713 fisheries worldwide, representing 78% of global reported fish
      catch, are analyzed to estimate the status, trends, and benefits of alternative
      approaches to recovering depleted fisheries. For each fishery, we estimate
      current biological status and forecast the impacts of contrasting management
      regimes on catch, profit, and biomass of fish in the sea. We estimate unique
      recovery targets and trajectories for each fishery, calculate the year-by-year
      effects of alternative recovery approaches, and model how alternative
      institutional reforms affect recovery outcomes. Current status is highly
      heterogeneous-the median fishery is in poor health (overfished, with further
      overfishing occurring), although 32% of fisheries are in good biological,
      although not necessarily economic, condition. Our business-as-usual scenario
      projects further divergence and continued collapse for many of the world's
      fisheries. Applying sound management reforms to global fisheries in our dataset
      could generate annual increases exceeding 16 million metric tons (MMT) in catch,
      $53 billion in profit, and 619 MMT in biomass relative to business as usual. We
      also find that, with appropriate reforms, recovery can happen quickly, with the
      median fishery taking under 10 y to reach recovery targets. Our results show that
      commonsense reforms to fishery management would dramatically improve overall fish
      abundance while increasing food security and profits.

PMID- 27035954
TI  - Sustained eruptions on Enceladus explained by turbulent dissipation in tiger
      stripes.
AB  - Spacecraft observations suggest that the plumes of Saturn's moon Enceladus draw
      water from a subsurface ocean, but the sustainability of conduits linking ocean
      and surface is not understood. Observations show eruptions from "tiger stripe"
      fissures that are sustained (although tidally modulated) throughout each orbit,
      and since the 2005 discovery of the plumes. Peak plume flux lags peak tidal
      extension by ~1 rad, suggestive of resonance. Here, we show that a model of the
      tiger stripes as tidally flexed slots that puncture the ice shell can
      simultaneously explain the persistence of the eruptions through the tidal cycle,
      the phase lag, and the total power output of the tiger stripe terrain, while
      suggesting that eruptions are maintained over geological timescales. The delay
      associated with flushing and refilling of O(1)-m-wide slots with ocean water
      causes erupted flux to lag tidal forcing and helps to buttress slots against
      closure, while tidally pumped in-slot flow leads to heating and mechanical
      disruption that staves off slot freezeout. Much narrower and much wider slots
      cannot be sustained. In the presence of long-lived slots, the 10(6)-y average
      power output of the tiger stripes is buffered by a feedback between ice melt-back
      and subsidence to O(10(10)) W, which is similar to observed power output,
      suggesting long-term stability. Turbulent dissipation makes testable predictions
      for the final flybys of Enceladus by Cassini Our model shows how open connections
      to an ocean can be reconciled with, and sustain, long-lived eruptions. Turbulent
      dissipation in long-lived slots helps maintain the ocean against freezing,
      maintains access by future Enceladus missions to ocean materials, and is
      plausibly the major energy source for tiger stripe activity. 

PMID- 27035956
TI  - Electric field-induced superconducting transition of insulating FeSe thin film at
      35 K.
AB  - It is thought that strong electron correlation in an insulating parent phase
      would enhance a critical temperature (Tc) of superconductivity in a doped phase
      via enhancement of the binding energy of a Cooper pair as known in high-Tc
      cuprates. To induce a superconductor transition in an insulating phase, injection
      of a high density of carriers is needed (e.g., by impurity doping). An electric
      double-layer transistor (EDLT) with an ionic liquid gate insulator enables such a
      field-induced transition to be investigated and is expected to result in a high
      Tc because it is free from deterioration in structure and carrier transport that
      are in general caused by conventional carrier doping (e.g., chemical
      substitution). Here, for insulating epitaxial thin films (~10 nm thick) of FeSe,
      we report a high Tc of 35 K, which is 4* higher than that of bulk FeSe, using an
      EDLT under application of a gate bias of +5.5 V. Hall effect measurements under
      the gate bias suggest that highly accumulated electron carrier in the channel,
      whose area density is estimated to be 1.4 * 10(15) cm(-2) (the average volume
      density of 1.7 * 10(21) cm(-3)), is the origin of the high-Tc superconductivity.
      This result demonstrates that EDLTs are useful tools to explore the ultimate Tc
      for insulating parent materials. 

PMID- 27035955
TI  - Structures of E. coli sigmaS-transcription initiation complexes provide new
      insights into polymerase mechanism.
AB  - In bacteria, multiple sigma factors compete to associate with the RNA polymerase
      (RNAP) core enzyme to form a holoenzyme that is required for promoter
      recognition. During transcription initiation RNAP remains associated with the
      upstream promoter DNA via sequence-specific interactions between the sigma factor
      and the promoter DNA while moving downstream for RNA synthesis. As RNA polymerase
      repetitively adds nucleotides to the 3'-end of the RNA, a pyrophosphate ion is
      generated after each nucleotide incorporation. It is currently unknown how the
      release of pyrophosphate affects transcription. Here we report the crystal
      structures of E coli transcription initiation complexes (TICs) containing the
      stress-responsive sigma(S) factor, a de novo synthesized RNA oligonucleotide, and
      a complete transcription bubble (sigma(S)-TIC) at about 3.9-A resolution. The
      structures show the 3D topology of the sigma(S) factor and how it recognizes the
      promoter DNA, including likely specific interactions with the template-strand
      residues of the -10 element. In addition, sigma(S)-TIC structures display a
      highly stressed pretranslocated initiation complex that traps a pyrophosphate at
      the active site that remains closed. The position of the pyrophosphate and the
      unusual phosphodiester linkage between the two terminal RNA residues suggest an
      unfinished nucleotide-addition reaction that is likely at equilibrium between
      nucleotide addition and pyrophosphorolysis. Although these sigma(S)-TIC crystals
      are enzymatically active, they are slow in nucleotide addition, as suggested by
      an NTP soaking experiment. Pyrophosphate release completes the nucleotide
      addition reaction and is associated with extensive conformational changes around
      the secondary channel but causes neither active site opening nor transcript
      translocation. 

PMID- 27035957
TI  - Spatial patterns of cutaneous vibration during whole-hand haptic interactions.
AB  - We investigated the propagation patterns of cutaneous vibration in the hand
      during interactions with touched objects. Prior research has highlighted the
      importance of vibrotactile signals during haptic interactions, but little is
      known of how vibrations propagate throughout the hand. Furthermore, the extent to
      which the patterns of vibrations reflect the nature of the objects that are
      touched, and how they are touched, is unknown. Using an apparatus comprised of an
      array of accelerometers, we mapped and analyzed spatial distributions of
      vibrations propagating in the skin of the dorsal region of the hand during active
      touch, grasping, and manipulation tasks. We found these spatial patterns of
      vibration to vary systematically with touch interactions and determined that it
      is possible to use these data to decode the modes of interaction with touched
      objects. The observed vibration patterns evolved rapidly in time, peaking in
      intensity within a few milliseconds, fading within 20-30 ms, and yielding
      interaction-dependent distributions of energy in frequency bands that span the
      range of vibrotactile sensitivity. These results are consistent with findings in
      perception research that indicate that vibrotactile information distributed
      throughout the hand can transmit information regarding explored and manipulated
      objects. The results may further clarify the role of distributed sensory
      resources in the perceptual recovery of object attributes during active touch,
      may guide the development of approaches to robotic sensing, and could have
      implications for the rehabilitation of the upper extremity. 

PMID- 27035958
TI  - S-nitrosation of proteins relevant to Alzheimer's disease during early stages of
      neurodegeneration.
AB  - Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational
      modification of cysteine thiols, is an important regulatory mechanism of protein
      function in both physiological and pathological pathways. A key first step toward
      elucidating the mechanism by which S-nitrosation modulates a protein's function
      is identification of the targeted cysteine residues. Here, we present a strategy
      for the simultaneous identification of SNO-cysteine sites and their cognate
      proteins to profile the brain of the CK-p25-inducible mouse model of Alzheimer's
      disease-like neurodegeneration. The approach-SNOTRAP (SNO trapping by triaryl
      phosphine)-is a direct tagging strategy that uses phosphine-based chemical
      probes, allowing enrichment of SNO-peptides and their identification by liquid
      chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO
      sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected
      only during neurodegeneration. S-nitrosation in the brain shows regional
      differences and becomes elevated during early stages of neurodegeneration in the
      CK-p25 mouse. The SNO-proteome during early neurodegeneration identified
      increased S-nitrosation of proteins important for synapse function, metabolism,
      and Alzheimer's disease pathology. In the latter case, proteins related to
      amyloid precursor protein processing and secretion are S-nitrosated, correlating
      with increased amyloid formation. Sequence analysis of SNO-cysteine sites
      identified potential linear motifs that are altered under pathological
      conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation
      of the SNO-proteome, providing functional insights of endogenous SNO proteins in
      the brain and its dysregulation during neurodegeneration. 

PMID- 27035959
TI  - Small-scale societies exhibit fundamental variation in the role of intentions in
      moral judgment.
AB  - Intent and mitigating circumstances play a central role in moral and legal
      assessments in large-scale industrialized societies. Although these features of
      moral assessment are widely assumed to be universal, to date, they have only been
      studied in a narrow range of societies. We show that there is substantial cross
      cultural variation among eight traditional small-scale societies (ranging from
      hunter-gatherer to pastoralist to horticulturalist) and two Western societies
      (one urban, one rural) in the extent to which intent and mitigating circumstances
      influence moral judgments. Although participants in all societies took such
      factors into account to some degree, they did so to very different extents,
      varying in both the types of considerations taken into account and the types of
      violations to which such considerations were applied. The particular patterns of
      assessment characteristic of large-scale industrialized societies may thus
      reflect relatively recently culturally evolved norms rather than inherent
      features of human moral judgment. 

PMID- 27035960
TI  - Stimuli-responsive clustered nanoparticles for improved tumor penetration and
      therapeutic efficacy.
AB  - A principal goal of cancer nanomedicine is to deliver therapeutics effectively to
      cancer cells within solid tumors. However, there are a series of biological
      barriers that impede nanomedicine from reaching target cells. Here, we report a
      stimuli-responsive clustered nanoparticle to systematically overcome these
      multiple barriers by sequentially responding to the endogenous attributes of the
      tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has
      an initial size of ~100 nm, which is favorable for long blood circulation and
      high propensity of extravasation through tumor vascular fenestrations. Once
      iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity
      would trigger the discharge of platinum prodrug-conjugated poly(amidoamine)
      dendrimers (diameter ~5 nm). Such a structural alteration greatly facilitates
      tumor penetration and cell internalization of the therapeutics. The internalized
      dendrimer prodrugs are further reduced intracellularly to release cisplatin to
      kill cancer cells. The superior in vivo antitumor activities of iCluster are
      validated in varying intractable tumor models including poorly permeable
      pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating
      its versatility and broad applicability. 

PMID- 27035961
TI  - Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.
AB  - Inherited demyelinating peripheral neuropathies are progressive incurable
      diseases without effective treatment. To develop a gene therapy approach
      targeting myelinating Schwann cells that can be translatable, we delivered a
      lentiviral vector using a single lumbar intrathecal injection and a myelin
      specific promoter. The human gene of interest, GJB1, which is mutated in X-linked
      Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1
      null mice, a genetically authentic model of CMT1X that develops a demyelinating
      peripheral neuropathy. We obtained widespread, stable, and cell-specific
      expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal
      roots and peripheral nerves. Behavioral and electrophysiological analysis
      revealed significantly improved motor performance, quadriceps muscle
      contractility, and sciatic nerve conduction velocities. Furthermore, treated mice
      exhibited reduced numbers of demyelinated and remyelinated fibers and fewer
      inflammatory cells in lumbar motor roots, as well as in the femoral motor and
      sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene
      delivery can lead to Schwann cell-specific expression in spinal roots extending
      to multiple peripheral nerves. This clinically relevant approach improves the
      phenotype of an inherited neuropathy mouse model and provides proof of principle
      for treating inherited demyelinating neuropathies. 

PMID- 27035962
TI  - Magnetic field evolution in magnetar crusts through three-dimensional
      simulations.
AB  - Current models of magnetars require extremely strong magnetic fields to explain
      their observed quiescent and bursting emission, implying that the field strength
      within the star's outer crust is orders of magnitude larger than the dipole
      component inferred from spin-down measurements. This presents a serious challenge
      to theories of magnetic field generation in a proto-neutron star. Here, we
      present detailed modeling of the evolution of the magnetic field in the crust of
      a neutron star through 3D simulations. We find that, in the plausible scenario of
      equipartition of energy between global-scale poloidal and toroidal magnetic
      components, magnetic instabilities transfer energy to nonaxisymmetric, kilometer
      sized magnetic features, in which the local field strength can greatly exceed
      that of the global-scale field. These intense small-scale magnetic features can
      induce high-energy bursts through local crust yielding, and the localized
      enhancement of Ohmic heating can power the star's persistent emission. Thus, the
      observed diversity in magnetar behavior can be explained with mixed poloidal
      toroidal fields of comparable energies. 

PMID- 27035963
TI  - Heterodimerization within the TREK channel subfamily produces a diverse family of
      highly regulated potassium channels.
AB  - Twik-related K(+) channel 1 (TREK1), TREK2, and Twik-related arachidonic-acid
      stimulated K(+) channel (TRAAK) form the TREK subfamily of two-pore-domain K(+)
      (K2P) channels. Despite sharing up to 78% sequence homology and overlapping
      expression profiles in the nervous system, these channels show major differences
      in their regulation by physiological stimuli. For instance, TREK1 is inhibited by
      external acidification, whereas TREK2 is activated. Here, we investigated the
      ability of the members of the TREK subfamily to assemble to form functional
      heteromeric channels with novel properties. Using single-molecule pull-down
      (SiMPull) from HEK cell lysate and subunit counting in the plasma membrane of
      living cells, we show that TREK1, TREK2, and TRAAK readily coassemble. TREK1 and
      TREK2 can each heterodimerize with TRAAK, but do so less efficiently than with
      each other. We functionally characterized the heterodimers and found that all
      combinations form outwardly rectifying potassium-selective channels but with
      variable voltage sensitivity and pH regulation. TREK1-TREK2 heterodimers show low
      levels of activity at physiological external pH but, unlike their corresponding
      homodimers, are activated by both acidic and alkaline conditions. Modeling based
      on recent crystal structures, along with mutational analysis, suggests that each
      subunit within a TREK1-TREK2 channel is regulated independently via titratable
      His. Finally, TREK1/TRAAK heterodimers differ in function from TRAAK homodimers
      in two critical ways: they are activated by both intracellular acidification and
      alkalinization and are regulated by the enzyme phospholipase D2. Thus,
      heterodimerization provides a means for diversifying functionality through an
      expansion of the channel types within the K2P channels. 

PMID- 27035964
TI  - Modeling and analysis of collective cell migration in an in vivo three
      dimensional environment.
AB  - A long-standing question in collective cell migration has been what might be the
      relative advantage of forming a cluster over migrating individually. Does an
      increase in the size of a collectively migrating group of cells enable them to
      sample the chemical gradient over a greater distance because the difference
      between front and rear of a cluster would be greater than for single cells? We
      combined theoretical modeling with experiments to study collective migration of
      the border cells in-between nurse cells in the Drosophila egg chamber. We
      discovered that cluster size is positively correlated with migration speed, up to
      a particular point above which speed plummets. This may be due to the effect of
      viscous drag from surrounding nurse cells together with confinement of all of the
      cells within a stiff extracellular matrix. The model predicts no relationship
      between cluster size and velocity for cells moving on a flat surface, in contrast
      to movement within a 3D environment. Our analyses also suggest that the overall
      chemoattractant profile in the egg chamber is likely to be exponential, with the
      highest concentration in the oocyte. These findings provide insights into
      collective chemotaxis by combining theoretical modeling with experimentation. 

PMID- 27035965
TI  - Mixing and matching TREK/TRAAK subunits generate heterodimeric K2P channels with
      unique properties.
AB  - The tandem of pore domain in a weak inwardly rectifying K(+) channel (Twik)
      related acid-arachidonic activated K(+) channel (TRAAK) and Twik-related K(+)
      channels (TREK) 1 and TREK2 are active as homodimers gated by stretch, fatty
      acids, pH, and G protein-coupled receptors. These two-pore domain potassium (K2P)
      channels are broadly expressed in the nervous system where they control
      excitability. TREK/TRAAK KO mice display altered phenotypes related to
      nociception, neuroprotection afforded by polyunsaturated fatty acids, learning
      and memory, mood control, and sensitivity to general anesthetics. These channels
      have emerged as promising targets for the development of new classes of
      anesthetics, analgesics, antidepressants, neuroprotective agents, and drugs
      against addiction. Here, we show that the TREK1, TREK2, and TRAAK subunits
      assemble and form active heterodimeric channels with electrophysiological,
      regulatory, and pharmacological properties different from those of homodimeric
      channels. Heteromerization occurs between all TREK variants produced by
      alternative splicing and alternative translation initiation. These results unveil
      a previously unexpected diversity of K2P channels that will be challenging to
      analyze in vivo, but which opens new perspectives for the development of
      clinically relevant drugs. 

PMID- 27035966
TI  - Reply to Stoet and Geary: Effects of gendered behavior on testosterone, not sex
      differences, as research focus.

PMID- 27035967
TI  - Comprehensive mutagenesis of the fimS promoter regulatory switch reveals novel
      regulation of type 1 pili in uropathogenic Escherichia coli.
AB  - Type 1 pili (T1P) are major virulence factors for uropathogenic Escherichia coli
      (UPEC), which cause both acute and recurrent urinary tract infections. T1P
      expression therefore is of direct relevance for disease. T1P are phase variable
      (both piliated and nonpiliated bacteria exist in a clonal population) and are
      controlled by an invertible DNA switch (fimS), which contains the promoter for
      the fim operon encoding T1P. Inversion of fimS is stochastic but may be biased by
      environmental conditions and other signals that ultimately converge at fimS
      itself. Previous studies of fimS sequences important for T1P phase variation have
      focused on laboratory-adapted E coli strains and have been limited in the number
      of mutations or by alteration of the fimS genomic context. We surmounted these
      limitations by using saturating genomic mutagenesis of fimS coupled with accurate
      sequencing to detect both mutations and phase status simultaneously. In addition
      to the sequences known to be important for biasing fimS inversion, our method
      also identifies a previously unknown pair of 5' UTR inverted repeats that act by
      altering the relative fimA levels to control phase variation. Thus we have
      uncovered an additional layer of T1P regulation potentially impacting virulence
      and the coordinate expression of multiple pilus systems. 

PMID- 27035968
TI  - Two distinct trimeric conformations of natively membrane-anchored full-length
      herpes simplex virus 1 glycoprotein B.
AB  - Many viruses are enveloped by a lipid bilayer acquired during assembly, which is
      typically studded with one or two types of glycoproteins. These viral surface
      proteins act as the primary interface between the virus and the host. Entry of
      enveloped viruses relies on specialized fusogen proteins to help merge the virus
      membrane with the host membrane. In the multicomponent herpesvirus fusion
      machinery, glycoprotein B (gB) acts as this fusogen. Although the structure of
      the gB ectodomain postfusion conformation has been determined, any other
      conformations (e.g., prefusion, intermediate conformations) have so far remained
      elusive, thus restricting efforts to develop antiviral treatments and
      prophylactic vaccines. Here, we have characterized the full-length herpes simplex
      virus 1 gB in a native membrane by displaying it on cell-derived vesicles and
      using electron cryotomography. Alongside the known postfusion conformation, a
      novel one was identified. Its structure, in the context of the membrane, was
      determined by subvolume averaging and found to be trimeric like the postfusion
      conformation, but appeared more condensed. Hierarchical constrained density
      fitting of domains unexpectedly revealed the fusion loops in this conformation to
      be apart and pointing away from the anchoring membrane. This vital observation is
      a substantial step forward in understanding the complex herpesvirus fusion
      mechanism, and opens up new opportunities for more targeted intervention of
      herpesvirus entry. 

PMID- 27035969
TI  - CRF binding protein facilitates the presence of CRF type 2alpha receptor on the
      cell surface.
AB  - Corticotropin releasing factor binding protein (CRF-BP) was originally recognized
      as CRF sequestering protein. However, its differential subcellular localization
      in different brain nuclei suggests that CRF-BP may have additional functions.
      There is evidence that CRF-BP potentiates CRF and urocortin 1 actions through CRF
      type 2 receptors (CRF2R). CRF2R is a G protein-coupled receptor (GPCR) that is
      found mainly intracellularly as most GPCRs. The access of GPCRs to the cell
      surface is tightly regulated by escort proteins. We hypothesized that CRF-BP
      binds to CRF2R, exerting an escort protein role. We analyzed the colocalization
      of CRF-BP and CRF2R in cultured rat mesencephalic neurons, and the localization
      and interaction of heterologous expressed CRF-BP and CRF2alphaR in yeast, human
      embryonic kidney 293, and rat pheochromocytoma 12 cells. Our results showed that
      CRF-BP and CRF2R naturally colocalize in the neurites of cultured mesencephalic
      neurons. Heterologous expression of each protein showed that CRF-BP was localized
      mainly in secretory granules and CRF2alphaR in the endoplasmic reticulum. In
      contrast, CRF-BP and CRF2alphaR colocalized when both proteins are coexpressed.
      Here we show that CRF-BP physically interacts with the CRF2alphaR but not the
      CRF2betaR isoform, increasing CRF2alphaR on the cell surface. Thus, CRF-BP
      emerges as a GPCR escort protein increasing the understanding of GPCR
      trafficking. 

PMID- 27035970
TI  - Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes
      selective autophagy of damaged mitochondria.
AB  - Selective autophagy of damaged mitochondria requires autophagy receptors
      optineurin (OPTN), NDP52 (CALCOCO2), TAX1BP1, and p62 (SQSTM1) linking
      ubiquitinated cargo to autophagic membranes. By using quantitative proteomics, we
      show that Tank-binding kinase 1 (TBK1) phosphorylates all four receptors on
      several autophagy-relevant sites, including the ubiquitin- and LC3-binding
      domains of OPTN and p62/SQSTM1 as well as the SKICH domains of NDP52 and TAX1BP1.
      Constitutive interaction of TBK1 with OPTN and the ability of OPTN to bind to
      ubiquitin chains are essential for TBK1 recruitment and kinase activation on
      mitochondria. TBK1 in turn phosphorylates OPTN's UBAN domain at S473, thereby
      expanding the binding capacity of OPTN to diverse Ub chains. In combination with
      phosphorylation of S177 and S513, this posttranslational modification promotes
      recruitment and retention of OPTN/TBK1 on ubiquitinated, damaged mitochondria.
      Moreover, phosphorylation of OPTN on S473 enables binding to pS65 Ub chains and
      is also implicated in PINK1-driven and Parkin-independent mitophagy. Thus, TBK1
      mediated phosphorylation of autophagy receptors creates a signal amplification
      loop operating in selective autophagy of damaged mitochondria. 

PMID- 27035971
TI  - Legumes are different: Leaf nitrogen, photosynthesis, and water use efficiency.
AB  - Using robust, pairwise comparisons and a global dataset, we show that nitrogen
      concentration per unit leaf mass for nitrogen-fixing plants (N2FP; mainly legumes
      plus some actinorhizal species) in nonagricultural ecosystems is universally
      greater (43-100%) than that for other plants (OP). This difference is maintained
      across Koppen climate zones and growth forms and strongest in the wet tropics and
      within deciduous angiosperms. N2FP mostly show a similar advantage over OP in
      nitrogen per leaf area (Narea), even in arid climates, despite diazotrophy being
      sensitive to drought. We also show that, for most N2FP, carbon fixation by
      photosynthesis (Asat) and stomatal conductance (gs) are not related to Narea-in
      distinct challenge to current theories that place the leaf nitrogen-Asat
      relationship at the center of explanations of plant fitness and competitive
      ability. Among N2FP, only forbs displayed an Narea-gs relationship similar to
      that for OP, whereas intrinsic water use efficiency (WUEi; Asat/gs) was
      positively related to Narea for woody N2FP. Enhanced foliar nitrogen (relative to
      OP) contributes strongly to other evolutionarily advantageous attributes of
      legumes, such as seed nitrogen and herbivore defense. These alternate
      explanations of clear differences in leaf N between N2FP and OP have significant
      implications (e.g., for global models of carbon fluxes based on relationships
      between leaf N and Asat). Combined, greater WUE and leaf nitrogen-in a variety of
      forms-enhance fitness and survival of genomes of N2FP, particularly in arid and
      semiarid climates. 

PMID- 27035972
TI  - Measuring and modeling diffuse scattering in protein X-ray crystallography.
AB  - X-ray diffraction has the potential to provide rich information about the
      structural dynamics of macromolecules. To realize this potential, both Bragg
      scattering, which is currently used to derive macromolecular structures, and
      diffuse scattering, which reports on correlations in charge density variations,
      must be measured. Until now, measurement of diffuse scattering from protein
      crystals has been scarce because of the extra effort of collecting diffuse data.
      Here, we present 3D measurements of diffuse intensity collected from crystals of
      the enzymes cyclophilin A and trypsin. The measurements were obtained from the
      same X-ray diffraction images as the Bragg data, using best practices for
      standard data collection. To model the underlying dynamics in a practical way
      that could be used during structure refinement, we tested translation-libration
      screw (TLS), liquid-like motions (LLM), and coarse-grained normal-modes (NM)
      models of protein motions. The LLM model provides a global picture of motions and
      was refined against the diffuse data, whereas the TLS and NM models provide more
      detailed and distinct descriptions of atom displacements, and only used
      information from the Bragg data. Whereas different TLS groupings yielded similar
      Bragg intensities, they yielded different diffuse intensities, none of which
      agreed well with the data. In contrast, both the LLM and NM models agreed
      substantially with the diffuse data. These results demonstrate a realistic path
      to increase the number of diffuse datasets available to the wider biosciences
      community and indicate that dynamics-inspired NM structural models can
      simultaneously agree with both Bragg and diffuse scattering. 

PMID- 27035973
TI  - Predation risk drives social complexity in cooperative breeders.
AB  - Predation risk is a major ecological factor selecting for group living. It is
      largely ignored, however, as an evolutionary driver of social complexity and
      cooperative breeding, which is attributed mainly to a combination of habitat
      saturation and enhanced relatedness levels. Social cichlids neither suffer from
      habitat saturation, nor are their groups composed primarily of relatives. This
      demands alternative ecological explanations for the evolution of advanced social
      organization. To address this question, we compared the ecology of eight
      populations of Neolamprologus pulcher, a cichlid fish arguably representing the
      pinnacle of social evolution in poikilothermic vertebrates. Results show that
      variation in social organization and behavior of these fish is primarily
      explained by predation risk and related ecological factors. Remarkably, ecology
      affects group structure more strongly than group size, with predation inversely
      affecting small and large group members. High predation and shelter limitation
      leads to groups containing few small but many large members, which is an effect
      enhanced at low population densities. Apparently, enhanced safety from predators
      by cooperative defense and shelter construction are the primary benefits of
      sociality. This finding suggests that predation risk can be fundamental for the
      transition toward complex social organization, which is generally undervalued. 

PMID- 27035974
TI  - [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine
      kinase activity.
AB  - Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic
      deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and
      positron emission tomography (PET) imaging target in cancer. PET probes for dCK
      have been developed and are effective in mice but have suboptimal specificity and
      sensitivity in humans. To identify a more suitable probe for clinical dCK PET
      imaging, we compared the selectivity of two candidate compounds
      [(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-beta-d-arabinofuranosyl
      adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-beta-d-arabinofuranosyl
      guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related
      mitochondrial enzyme. We demonstrate that, in the tracer concentration range used
      for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross
      reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for
      dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and
      was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was
      reduced by deoxycytidine (dC) competition, this inhibition required high dC
      concentrations present in murine, but not human, plasma. Expression of cytidine
      deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and
      in mice reduced the competition between dC and [(18)F]CFA, leading to increased
      dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA
      PET/CT studies showed probe accumulation in tissues with high dCK expression:
      e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of
      [(18)F]CFA for dCK and its favorable biodistribution in humans justify further
      studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment
      stratification and monitoring. 

PMID- 27035975
TI  - A bacterial Argonaute with noncanonical guide RNA specificity.
AB  - Eukaryotic Argonaute proteins induce gene silencing by small RNA-guided
      recognition and cleavage of mRNA targets. Although structural similarities
      between human and prokaryotic Argonautes are consistent with shared mechanistic
      properties, sequence and structure-based alignments suggested that Argonautes
      encoded within CRISPR-cas [clustered regularly interspaced short palindromic
      repeats (CRISPR)-associated] bacterial immunity operons have divergent
      activities. We show here that the CRISPR-associated Marinitoga piezophila
      Argonaute (MpAgo) protein cleaves single-stranded target sequences using 5'
      hydroxylated guide RNAs rather than the 5'-phosphorylated guides used by all
      known Argonautes. The 2.0-A resolution crystal structure of an MpAgo-RNA complex
      reveals a guide strand binding site comprising residues that block 5' phosphate
      interactions. Using structure-based sequence alignment, we were able to identify
      other putative MpAgo-like proteins, all of which are encoded within CRISPR-cas
      loci. Taken together, our data suggest the evolution of an Argonaute subclass
      with noncanonical specificity for a 5'-hydroxylated guide. 

PMID- 27035976
TI  - Host-parasite oscillation dynamics and evolution in a compartmentalized RNA
      replication system.
AB  - To date, various cellular functions have been reconstituted in vitro such as self
      replication systems using DNA, RNA, and proteins. The next important challenges
      include the reconstitution of the interactive networks of self-replicating
      species and investigating how such interactions generate complex ecological
      behaviors observed in nature. Here, we synthesized a simple replication system
      composed of two self-replicating host and parasitic RNA species. We found that
      the parasitic RNA eradicates the host RNA under bulk conditions; however, when
      the system is compartmentalized, a continuous oscillation pattern in the
      population dynamics of the two RNAs emerges. The oscillation pattern changed as
      replication proceeded mainly owing to the evolution of the host RNA. These
      results demonstrate that a cell-like compartment plays an important role in host
      parasite ecological dynamics and suggest that the origin of the host-parasite
      coevolution might date back to the very early stages of the evolution of life. 

PMID- 27035977
TI  - Engineering titania nanostructure to tune and improve its photocatalytic
      activity.
AB  - Photocatalytic pathways could prove crucial to the sustainable production of
      fuels and chemicals required for a carbon-neutral society. Electron-hole
      recombination is a critical problem that has, so far, limited the efficiency of
      the most promising photocatalytic materials. Here, we show the efficacy of
      anisotropy in improving charge separation and thereby boosting the activity of a
      titania (TiO2) photocatalytic system. Specifically, we show that H2 production in
      uniform, one-dimensional brookite titania nanorods is highly enhanced by
      engineering their length. By using complimentary characterization techniques to
      separately probe excited electrons and holes, we link the high observed reaction
      rates to the anisotropic structure, which favors efficient carrier utilization.
      Quantum yield values for hydrogen production from ethanol, glycerol, and glucose
      as high as 65%, 35%, and 6%, respectively, demonstrate the promise and generality
      of this approach for improving the photoactivity of semiconducting nanostructures
      for a wide range of reacting systems. 

PMID- 27035978
TI  - Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes
      neurotoxicity in zebrafish.
AB  - Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely
      used in cancer treatment and in a number of curative and palliative regimens.
      Despite its beneficial effects on cancer, paclitaxel also damages healthy
      tissues, most prominently the peripheral sensory nervous system. The mechanisms
      leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies
      that prevent or alleviate this condition are not available. We established a
      zebrafish in vivo model to study the underlying mechanisms and to identify
      pharmacological agents that may be developed into therapeutics. Both adult and
      larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory
      axon degeneration and the loss of touch response in the distal caudal fin.
      Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes
      epithelial damage and decreased mechanical stress resistance of the skin before
      induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish
      skin and scratch-wounded human keratinocytes (HEK001) display reduced healing
      capacity. Epithelial damage correlated with rapid accumulation of fluorescein
      conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up
      regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin.
      Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel
      induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in
      zebrafish embryos rendered the skin vulnerable to injury under mechanical stress
      conditions. Thus, our studies provide evidence that the epidermis plays a
      critical role in this condition, and we provide a previously unidentified
      candidate for therapeutic interventions.

PMID- 27035979
TI  - Stokes trap for multiplexed particle manipulation and assembly using fluidics.
AB  - The ability to confine and manipulate single particles and molecules has
      revolutionized several fields of science. Hydrodynamic trapping offers an
      attractive method for particle manipulation in free solution without the need for
      optical, electric, acoustic, or magnetic fields. Here, we develop and demonstrate
      the Stokes trap, which is a new method for trapping multiple particles using only
      fluid flow. We demonstrate simultaneous manipulation of two particles in a simple
      microfluidic device using model predictive control. We further show that this
      approach can be used for fluidic-directed assembly of multiple particles in
      solution. Overall, this technique opens new vistas for fundamental studies of
      particle-particle interactions and provides a new method for the directed
      assembly of colloidal particles. 

PMID- 27035981
TI  - Turbulent dynamo in a collisionless plasma.
AB  - Magnetic fields pervade the entire universe and affect the formation and
      evolution of astrophysical systems from cosmological to planetary scales. The
      generation and dynamical amplification of extragalactic magnetic fields through
      cosmic times (up to microgauss levels reported in nearby galaxy clusters, near
      equipartition with kinetic energy of plasma motions, and on scales of at least
      tens of kiloparsecs) are major puzzles largely unconstrained by observations. A
      dynamo effect converting kinetic flow energy into magnetic energy is often
      invoked in that context; however, extragalactic plasmas are weakly collisional
      (as opposed to magnetohydrodynamic fluids), and whether magnetic field growth and
      sustainment through an efficient turbulent dynamo instability are possible in
      such plasmas is not established. Fully kinetic numerical simulations of the
      Vlasov equation in a 6D-phase space necessary to answer this question have, until
      recently, remained beyond computational capabilities. Here, we show by means of
      such simulations that magnetic field amplification by dynamo instability does
      occur in a stochastically driven, nonrelativistic subsonic flow of initially
      unmagnetized collisionless plasma. We also find that the dynamo self-accelerates
      and becomes entangled with kinetic instabilities as magnetization increases. The
      results suggest that such a plasma dynamo may be realizable in laboratory
      experiments, support the idea that intracluster medium turbulence may have
      significantly contributed to the amplification of cluster magnetic fields up to
      near-equipartition levels on a timescale shorter than the Hubble time, and
      emphasize the crucial role of multiscale kinetic physics in high-energy
      astrophysical plasmas. 

PMID- 27035980
TI  - Radical remodeling of the Y chromosome in a recent radiation of malaria
      mosquitoes.
AB  - Y chromosomes control essential male functions in many species, including sex
      determination and fertility. However, because of obstacles posed by repeat-rich
      heterochromatin, knowledge of Y chromosome sequences is limited to a handful of
      model organisms, constraining our understanding of Y biology across the tree of
      life. Here, we leverage long single-molecule sequencing to determine the content
      and structure of the nonrecombining Y chromosome of the primary African malaria
      mosquito, Anopheles gambiae We find that the An. gambiae Y consists almost
      entirely of a few massively amplified, tandemly arrayed repeats, some of which
      can recombine with similar repeats on the X chromosome. Sex-specific genome
      resequencing in a recent species radiation, the An. gambiae complex, revealed
      rapid sequence turnover within An. gambiae and among species. Exploiting 52 sex
      specific An. gambiae RNA-Seq datasets representing all developmental stages, we
      identified a small repertoire of Y-linked genes that lack X gametologs and are
      not Y-linked in any other species except An. gambiae, with the notable exception
      of YG2, a candidate male-determining gene. YG2 is the only gene conserved and
      exclusive to the Y in all species examined, yet sequence similarity to YG2 is not
      detectable in the genome of a more distant mosquito relative, suggesting rapid
      evolution of Y chromosome genes in this highly dynamic genus of malaria vectors.
      The extensive characterization of the An. gambiae Y provides a long-awaited
      foundation for studying male mosquito biology, and will inform novel mosquito
      control strategies based on the manipulation of Y chromosomes. 

PMID- 27035982
TI  - Functional architecture of the Reb1-Ter complex of Schizosaccharomyces pombe.
AB  - Reb1 ofSchizosaccharomyces pomberepresents a family of multifunctional proteins
      that bind to specific terminator sites (Ter) and cause polar termination of
      transcription catalyzed by RNA polymerase I (pol I) and arrest of replication
      forks approaching the Ter sites from the opposite direction. However, it remains
      to be investigated whether the same mechanism causes arrest of both DNA
      transactions. Here, we present the structure of Reb1 as a complex with a Ter site
      at a resolution of 2.7 A. Structure-guided molecular genetic analyses revealed
      that it has distinct and well-defined DNA binding and transcription termination
      (TTD) domains. The region of the protein involved in replication termination is
      distinct from the TTD. Mechanistically, the data support the conclusion that
      transcription termination is not caused by just high affinity Reb1-Ter protein
      DNA interactions. Rather, protein-protein interactions between the TTD with the
      Rpa12 subunit of RNA pol I seem to be an integral part of the mechanism. This
      conclusion is further supported by the observation that double mutations in TTD
      that abolished its interaction with Rpa12 also greatly reduced transcription
      termination thereby revealing a conduit for functional communications between RNA
      pol I and the terminator protein. 

PMID- 27035983
TI  - Identification of tumorigenic cells and therapeutic targets in pancreatic
      neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors (PanNETs) are a type of pancreatic cancer with
      limited therapeutic options. Consequently, most patients with advanced disease
      die from tumor progression. Current evidence indicates that a subset of cancer
      cells is responsible for tumor development, metastasis, and recurrence, and
      targeting these tumor-initiating cells is necessary to eradicate tumors. However,
      tumor-initiating cells and the biological processes that promote pathogenesis
      remain largely uncharacterized in PanNETs. Here we profile primary and metastatic
      tumors from an index patient and demonstrate that MET proto-oncogene activation
      is important for tumor growth in PanNET xenograft models. We identify a highly
      tumorigenic cell population within several independent surgically acquired
      PanNETs characterized by increased cell-surface protein CD90 expression and
      aldehyde dehydrogenase A1 (ALDHA1) activity, and provide in vitro and in vivo
      evidence for their stem-like properties. We performed proteomic profiling of 332
      antigens in two cell lines and four primary tumors, and showed that CD47, a cell
      surface protein that acts as a "don't eat me" signal co-opted by cancers to evade
      innate immune surveillance, is ubiquitously expressed. Moreover, CD47 coexpresses
      with MET and is enriched in CD90(hi)cells. Furthermore, blocking CD47 signaling
      promotes engulfment of tumor cells by macrophages in vitro and inhibits xenograft
      tumor growth, prevents metastases, and prolongs survival in vivo. 

PMID- 27035984
TI  - Simultaneous single-molecule epigenetic imaging of DNA methylation and
      hydroxymethylation.
AB  - The modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are
      the two major DNA epigenetic modifications in mammalian genomes and play crucial
      roles in development and pathogenesis. Little is known about the colocalization
      or potential correlation of these two modifications. Here we present an
      ultrasensitive single-molecule imaging technology capable of detecting and
      quantifying 5hmC and 5mC from trace amounts of DNA. We used this approach to
      perform single-molecule fluorescence resonance energy transfer (smFRET)
      experiments which measure the proximity between 5mC and 5hmC in the same DNA
      molecule. Our results reveal high levels of adjacent and opposing methylated and
      hydroxymethylated CpG sites (5hmC/5mCpGs) in mouse genomic DNA across multiple
      tissues. This identifies the previously undetectable and unappreciated
      5hmC/5mCpGs as one of the major states for 5hmC in the mammalian genome and
      suggest that they could function in promoting gene expression. 

PMID- 27035985
TI  - No evidence for extensive horizontal gene transfer in the genome of the
      tardigrade Hypsibius dujardini.
AB  - Tardigrades are meiofaunal ecdysozoans that are key to understanding the origins
      of Arthropoda. Many species of Tardigrada can survive extreme conditions through
      cryptobiosis. In a recent paper [Boothby TC, et al. (2015) Proc Natl Acad Sci USA
      112(52):15976-15981], the authors concluded that the tardigrade Hypsibius
      dujardini had an unprecedented proportion (17%) of genes originating through
      functional horizontal gene transfer (fHGT) and speculated that fHGT was likely
      formative in the evolution of cryptobiosis. We independently sequenced the genome
      of H. dujardini As expected from whole-organism DNA sampling, our raw data
      contained reads from nontarget genomes. Filtering using metagenomics approaches
      generated a draft H. dujardini genome assembly of 135 Mb with superior assembly
      metrics to the previously published assembly. Additional microbial contamination
      likely remains. We found no support for extensive fHGT. Among 23,021 gene
      predictions we identified 0.2% strong candidates for fHGT from bacteria and 0.2%
      strong candidates for fHGT from nonmetazoan eukaryotes. Cross-comparison of
      assemblies showed that the overwhelming majority of HGT candidates in the Boothby
      et al. genome derived from contaminants. We conclude that fHGT into H. dujardini
      accounts for at most 1-2% of genes and that the proposal that one-sixth of
      tardigrade genes originate from functional HGT events is an artifact of
      undetected contamination.

PMID- 27035987
TI  - Output-driven feedback system control platform optimizes combinatorial therapy of
      tuberculosis using a macrophage cell culture model.
AB  - Tuberculosis (TB) remains a major global public health problem, and improved
      treatments are needed to shorten duration of therapy, decrease disease burden,
      improve compliance, and combat emergence of drug resistance. Ideally, the most
      effective regimen would be identified by a systematic and comprehensive
      combinatorial search of large numbers of TB drugs. However, optimization of
      regimens by standard methods is challenging, especially as the number of drugs
      increases, because of the extremely large number of drug-dose combinations
      requiring testing. Herein, we used an optimization platform, feedback system
      control (FSC) methodology, to identify improved drug-dose combinations for TB
      treatment using a fluorescence-based human macrophage cell culture model of TB,
      in which macrophages are infected with isopropyl beta-D-1-thiogalactopyranoside
      (IPTG)-inducible green fluorescent protein (GFP)-expressing Mycobacterium
      tuberculosis (Mtb). On the basis of only a single screening test and three
      iterations, we identified highly efficacious three- and four-drug combinations.
      To verify the efficacy of these combinations, we further evaluated them using a
      methodologically independent assay for intramacrophage killing of Mtb; the
      optimized combinations showed greater efficacy than the current standard TB drug
      regimen. Surprisingly, all top three- and four-drug optimized regimens included
      the third-line drug clofazimine, and none included the first-line drugs isoniazid
      and rifampin, which had insignificant or antagonistic impacts on efficacy.
      Because top regimens also did not include a fluoroquinolone or aminoglycoside,
      they are potentially of use for treating many cases of multidrug- and extensively
      drug-resistant TB. Our study shows the power of an FSC platform to identify
      promising previously unidentified drug-dose combinations for treatment of TB. 

PMID- 27035986
TI  - DELAY OF GERMINATION1 (DOG1) regulates both seed dormancy and flowering time
      through microRNA pathways.
AB  - Seed germination and flowering, two critical developmental transitions in plant
      life cycles, are coordinately regulated by genetic and environmental factors to
      match plant establishment and reproduction to seasonal cues. The DELAY OF
      GERMINATION1 (DOG1) gene is involved in regulating seed dormancy in response to
      temperature and has also been associated genetically with pleiotropic flowering
      phenotypes across diverse Arabidopsis thaliana accessions and locations. Here we
      show that DOG1 can regulate seed dormancy and flowering times in lettuce (Lactuca
      sativa, Ls) and Arabidopsis through an influence on levels of microRNAs (miRNAs)
      miR156 and miR172. In lettuce, suppression of LsDOG1 expression enabled seed
      germination at high temperature and promoted early flowering in association with
      reduced miR156 and increased miR172 levels. In Arabidopsis, higher miR156 levels
      resulting from overexpression of the MIR156 gene enhanced seed dormancy and
      delayed flowering. These phenotypic effects, as well as conversion of MIR156
      transcripts to miR156, were compromised in DOG1 loss-of-function mutant plants,
      especially in seeds. Overexpression of MIR172 reduced seed dormancy and promoted
      early flowering in Arabidopsis, and the effect on flowering required functional
      DOG1 Transcript levels of several genes associated with miRNA processing were
      consistently lower in dry seeds of Arabidopsis and lettuce when DOG1 was mutated
      or its expression was reduced; in contrast, transcript levels of these genes were
      elevated in a DOG1 gain-of-function mutant. Our results reveal a previously
      unknown linkage between two critical developmental phase transitions in the plant
      life cycle through a DOG1-miR156-miR172 interaction.

PMID- 27035988
TI  - Endocrine vasculatures are preferable targets of an antitumor ineffective low
      dose of anti-VEGF therapy.
AB  - Anti-VEGF-based antiangiogenic drugs are designed to block tumor angiogenesis for
      treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target
      effects on multiple tissues and organs and cause broad adverse effects. Here, we
      show that vasculatures in endocrine organs were more sensitive to anti-VEGF
      treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic
      islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody
      caused marked vascular regression, whereas tumor vessels remained unaffected.
      Additionally, a low dose of VEGF blockade significantly inhibited the formation
      of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along
      with vascular structural changes, the low dose of VEGF blockade inhibited
      vascular perfusion and permeability in thyroid, but not in tumors. Prolonged
      treatment with the low-dose VEGF blockade caused hypertension and significantly
      decreased circulating levels of thyroid hormone free-T3 and -T4, leading to
      functional impairment of thyroid. These findings show that the fenestrated
      microvasculatures in endocrine organs are more sensitive than tumor vasculatures
      in response to systemic anti-VEGF drugs. Thus, our data support the notion that
      clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause
      adverse effects. 

PMID- 27035989
TI  - Engineering a long-acting, potent GLP-1 analog for microstructure-based
      transdermal delivery.
AB  - Antidiabetic treatments aiming to reduce body weight are currently gaining
      increased interest. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist
      administered twice daily via s.c. injection, improves glycemic control, often
      with associated weight reduction. To further improve the therapeutic efficacy of
      exendin-4, we have developed a novel peptide engineering strategy that
      incorporates a serum protein binding motif onto a covalent side-chain staple and
      applied to the peptide to enhance its helicity and, as a consequence, its potency
      and serum half-life. We demonstrated that one of the resulting peptides, E6, has
      significantly improved half-life and glucose tolerance in an oral glucose
      tolerance test in rodents. Chronic treatment of E6 significantly decreased body
      weight and fasting blood glucose, improved lipid metabolism, and also reduced
      hepatic steatosis in diet-induced obese mice. Moreover, the high potency of E6
      allowed us to administer this peptide using a dissolvable microstructure-based
      transdermal delivery system. Pharmacokinetic and pharmacodynamic studies in
      guinea pigs showed that a single 5-min application of a microstructure system
      containing E6 significantly improved glucose tolerance for 96 h. This delivery
      strategy may offer an effective and patient-friendly alternative to currently
      marketed GLP-1 injectables and can likely be extended to other peptide hormones. 

PMID- 27035990
TI  - Rethinking progesterone regulation of female reproductive cyclicity.
AB  - The progesterone receptor (PGR) is a ligand-activated transcription factor with
      key roles in the regulation of female fertility. Much has been learned of the
      actions of PGR signaling through the use of pharmacologic inhibitors and genetic
      manipulation, using mouse mutagenesis. Characterization of rats with a null
      mutation at the Pgr locus has forced a reexamination of the role of progesterone
      in the regulation of the female reproductive cycle. We generated two Pgr mutant
      rat models, using genome editing. In both cases, deletions yielded a null
      mutation resulting from a nonsense frame-shift and the emergence of a stop codon.
      Similar to Pgr null mice, Pgr null rats were infertile because of deficits in
      sexual behavior, ovulation, and uterine endometrial differentiation. However, in
      contrast to the reported phenotype of female mice with disruptions in Pgr
      signaling, Pgr null female rats exhibit robust estrous cycles. Cyclic changes in
      vaginal cytology, uterine histology, serum hormone levels, and wheel running
      activity were evident in Pgr null female rats, similar to wild-type controls.
      Furthermore, exogenous progesterone treatment inhibited estrous cycles in wild
      type female rats but not in Pgr-null female rats. As previously reported,
      pharmacologic antagonism supports a role for PGR signaling in the regulation of
      the ovulatory gonadotropin surge, a result at variance with experimentation using
      genetic ablation of PGR signaling. To conclude, our findings in the Pgr null rat
      challenge current assumptions and prompt a reevaluation of the hormonal control
      of reproductive cyclicity. 

PMID- 27035991
TI  - Evolutionary clash between myxoma virus and rabbit PKR in Australia.

PMID- 27035992
TI  - Rating antifreeze proteins: Not a breeze.

PMID- 27035993
TI  - Markedly enhanced absorption and direct radiative forcing of black carbon under
      polluted urban environments.
AB  - Black carbon (BC) exerts profound impacts on air quality and climate because of
      its high absorption cross-section over a broad range of electromagnetic spectra,
      but the current results on absorption enhancement of BC particles during
      atmospheric aging remain conflicting. Here, we quantified the aging and variation
      in the optical properties of BC particles under ambient conditions in Beijing,
      China, and Houston, United States, using a novel environmental chamber approach.
      BC aging exhibits two distinct stages, i.e., initial transformation from a
      fractal to spherical morphology with little absorption variation and subsequent
      growth of fully compact particles with a large absorption enhancement. The
      timescales to achieve complete morphology modification and an absorption
      amplification factor of 2.4 for BC particles are estimated to be 2.3 h and 4.6 h,
      respectively, in Beijing, compared with 9 h and 18 h, respectively, in Houston.
      Our findings indicate that BC under polluted urban environments could play an
      essential role in pollution development and contribute importantly to large
      positive radiative forcing. The variation in direct radiative forcing is
      dependent on the rate and timescale of BC aging, with a clear distinction between
      urban cities in developed and developing countries, i.e., a higher climatic
      impact in more polluted environments. We suggest that mediation in BC emissions
      achieves a cobenefit in simultaneously controlling air pollution and protecting
      climate, especially for developing countries. 

PMID- 27035994
TI  - On board a raft or boat in the retrovirus sea.
AB  - This article summarizes the essential steps in understanding the chicken Rous
      sarcoma virus (RSV) genome association with a nonpermissive rodent host cell
      genome. This insight was made possible by in-depth study of RSV-transformed rat
      XC cells, which were called virogenic because they indefinitely carry virus
      genetic information in the absence of any infectious virus production. However,
      the virus was rescued by association of XC cells with chicken fibroblasts,
      allowing cell fusion between both partners. This and additional studies led to
      the interpretation that the RSV genome gets integrated into the host cell genome
      as a provirus. Study of additional rodent virogenic cell lines provided evidence
      that the transcript of oncogene v-src can be transmitted to other retroviruses
      and produce cell transformation by itself. As discussed in the text, two main
      questions related to nonpermissiveness to retrovirus infection remain to be
      solved. The first is changes in the retrovirus envelope gene allowing virus entry
      into a nonpermissive cell. The second is the nature of the permissive cell
      functions required by the nonpermissive cell to ensure infectious virus
      production. Both lines of investigation are being pursued. 

PMID- 27035995
TI  - Land-use policies and corporate investments in agriculture in the Gran Chaco and
      Chiquitano.
AB  - Growing demand for agricultural commodities is causing the expansion of
      agricultural frontiers onto native vegetation worldwide. Agribusiness companies
      linking these frontiers to distant spaces of consumption through global commodity
      chains increasingly make zero-deforestation pledges. However, production and land
      conversion are often carried out by less-visible local and regional actors that
      are mobile and responsive to new agricultural expansion opportunities and legal
      constraints on land use. With more stringent deforestation regulations in some
      countries, we ask whether their movements are determined partly by differences in
      land-use policies, resulting in "deforestation havens." We analyze the
      determinants of investment decisions by agricultural companies in the Gran Chaco
      and Chiquitano, a region that has become the new deforestation "hot spot" in
      South America. We test whether companies seek out less-regulated forest areas for
      new agricultural investments. Based on interviews with 82 companies totaling 2.5
      Mha of properties, we show that, in addition to proximity to current investments
      and the availability of cheap forestland, lower deforestation regulations attract
      investments by companies that tend to clear more forest, mostly cattle ranching
      operations, and that lower enforcement attracts all companies. Avoiding
      deforestation leakage requires harmonizing deforestation regulations across
      regions and commodities and promoting sustainable intensification in cattle
      ranching. 

PMID- 27035996
TI  - Measurement of Fukushima-related radioactive contamination in aquatic species.

PMID- 27035997
TI  - Enhanced gene targeting to evaluate Lynch syndrome alterations.

PMID- 27035998
TI  - Rise, stagnation, and rise of Danish women's life expectancy.
AB  - Health conditions change from year to year, with a general tendency in many
      countries for improvement. These conditions also change from one birth cohort to
      another: some generations suffer more adverse events in childhood, smoke more
      heavily, eat poorer diets, etc., than generations born earlier or later. Because
      it is difficult to disentangle period effects from cohort effects, demographers,
      epidemiologists, actuaries, and other population scientists often disagree about
      cohort effects' relative importance. In particular, some advocate forecasts of
      life expectancy based on period trends; others favor forecasts that hinge on
      cohort differences. We use a combination of age decomposition and exchange of
      survival probabilities between countries to study the remarkable recent history
      of female life expectancy in Denmark, a saga of rising, stagnating, and now again
      rising lifespans. The gap between female life expectancy in Denmark vs. Sweden
      grew to 3.5 y in the period 1975-2000. When we assumed that Danish women born
      1915-1945 had the same survival probabilities as Swedish women, the gap remained
      small and roughly constant. Hence, the lower Danish life expectancy is caused by
      these cohorts and is not attributable to period effects. 

PMID- 27035999
TI  - Heterochromatin and genetic conflict.

PMID- 27036000
TI  - Three-dimensional architecture of Vibrio cholera biofilms.

PMID- 27036001
TI  - Individual variability in human blood metabolites identifies age-related
      differences.
AB  - Metabolites present in human blood document individual physiological states
      influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution
      liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted,
      quantitative metabolomics analysis in blood of 15 young (29 +/- 4 y of age) and
      15 elderly (81 +/- 7 y of age) individuals. Coefficients of variation (CV =
      SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC
      enriched metabolites, for which metabolomics studies have been scarce, are
      highlighted here. We found 14 blood compounds that show remarkable age-related
      increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine,
      acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine,N-acetyl
      arginine,N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD(+),
      and NADP(+) Six of them are RBC-enriched, suggesting that RBC metabolomics is
      highly valuable for human aging research. Age differences are partly explained by
      a decrease in antioxidant production or increasing inefficiency of urea
      metabolism among the elderly. Pearson's coefficients demonstrated that some age
      related compounds are correlated, suggesting that aging affects them
      concomitantly. Although our CV values are mostly consistent with those CVs
      previously published, we here report previously unidentified CVs of 51 blood
      compounds. Compounds having moderate to high CV values (0.4-2.5) are often
      modified. Compounds having low CV values, such as ATP and glutathione, may be
      related to various diseases because their concentrations are strictly controlled,
      and changes in them would compromise health. Thus, human blood is a rich source
      of information about individual metabolic differences. 

PMID- 27036002
TI  - Surface force measurements and simulations of mussel-derived peptide adhesives on
      wet organic surfaces.
AB  - Translating sticky biological molecules-such as mussel foot proteins (MFPs)-into
      synthetic, cost-effective underwater adhesives with adjustable nano- and
      macroscale characteristics requires an intimate understanding of the glue's
      molecular interactions. To help facilitate the next generation of aqueous
      adhesives, we performed a combination of surface forces apparatus (SFA)
      measurements and replica-exchange molecular dynamics (REMD) simulations on a
      synthetic, easy to prepare, Dopa-containing peptide (MFP-3s peptide), which
      adheres to organic surfaces just as effectively as its wild-type protein analog.
      Experiments and simulations both show significant differences in peptide
      adsorption on CH3-terminated (hydrophobic) and OH-terminated (hydrophilic) self
      assembled monolayers (SAMs), where adsorption is strongest on hydrophobic SAMs
      because of orientationally specific interactions with Dopa. Additional umbrella
      sampling simulations yield free-energy profiles that quantitatively agree with
      SFA measurements and are used to extract the adhesive properties of individual
      amino acids within the context of MFP-3s peptide adhesion, revealing a delicate
      balance between van der Waals, hydrophobic, and electrostatic forces. 

PMID- 27036004
TI  - QnAs with Jan Svoboda.

PMID- 27036003
TI  - Molecular basis for universal HLA-A*0201-restricted CD8+ T-cell immunity against
      influenza viruses.
AB  - Memory CD8(+)T lymphocytes (CTLs) specific for antigenic peptides derived from
      internal viral proteins confer broad protection against distinct strains of
      influenza A virus (IAV). However, immune efficacy can be undermined by the
      emergence of escape mutants. To determine how T-cell receptor (TCR) composition
      relates to IAV epitope variability, we used ex vivo peptide-HLA tetramer
      enrichment and single-cell multiplex analysis to compare TCRs targeted to the
      largely conserved HLA-A*0201-M158and the hypervariable HLA-B*3501-NP418antigens.
      The TCRalphabetas for HLA-B*3501-NP418 (+)CTLs varied among individuals and
      across IAV strains, indicating that a range of mutated peptides will prime
      different NP418-specific CTL sets. Conversely, a dominant public
      TRAV27/TRBV19(+)TCRalphabeta was selected in HLA-A*0201(+)donors responding to
      M158 This public TCR cross-recognized naturally occurring M158variants complexed
      with HLA-A*0201. Ternary structures showed that induced-fit molecular mimicry
      underpins TRAV27/TRBV19(+)TCR specificity for the WT and mutant M158peptides,
      suggesting the possibility of universal CTL immunity in HLA-A*0201(+)individuals.
      Combined with the high population frequency of HLA-A*0201, these data potentially
      explain the relative conservation of M158 Moreover, our results suggest that
      vaccination strategies aimed at generating broad protection should incorporate
      variant peptides to elicit cross-reactive responses against other specificities,
      especially those that may be relatively infrequent among IAV-primed memory CTLs. 

PMID- 27036005
TI  - Stress management strategies in single bacterial cells.

PMID- 27036006
TI  - Genome-wide kinetics of DNA excision repair in relation to chromatin state and
      mutagenesis.
AB  - We recently developed a high-resolution genome-wide assay for mapping DNA
      excision repair named eXcision Repair-sequencing (XR-seq) and have now used XR
      seq to determine which regions of the genome are subject to repair very soon
      after UV exposure and which regions are repaired later. Over a time course, we
      measured repair of the UV-induced damage of cyclobutane pyrimidine dimers (CPDs)
      (at 1, 4, 8, 16, 24, and 48 h) and (6-4)pyrimidine-pyrimidone photoproducts [(6
      4)PPs] (at 5 and 20 min and 1, 2, and 4 h) in normal human skin fibroblasts. Each
      type of damage has distinct repair kinetics. The (6-4)PPs are detected as early
      as 5 min after UV treatment, with the bulk of repair completed by 4 h. Repair of
      CPDs, which we previously showed is intimately coupled to transcription, is
      slower and in certain regions persists even 2 d after UV irradiation. We compared
      our results to the Encyclopedia of DNA Elements data regarding histone
      modifications, chromatin state, and transcription. For both damage types, and for
      both transcription-coupled and general excision repair, the earliest repair
      occurred preferentially in active and open chromatin states. Conversely, repair
      in regions classified as "heterochromatic" and "repressed" was relatively low at
      early time points, with repair persisting into the late time points. Damage that
      remains during DNA replication increases the risk for mutagenesis. Indeed, late
      repaired regions are associated with a higher level of cancer-linked mutations.
      In summary, we show that XR-seq is a powerful approach for studying relationships
      among chromatin state, DNA repair, genome stability, mutagenesis, and
      carcinogenesis. 

PMID- 27036007
TI  - Anabolic actions of Notch on mature bone.
AB  - Notch controls skeletogenesis, but its role in the remodeling of adult bone
      remains conflicting. In mature mice, the skeleton can become osteopenic or
      osteosclerotic depending on the time point at which Notch is activated or
      inactivated. Using adult EGFP reporter mice, we find that Notch expression is
      localized to osteocytes embedded within bone matrix. Conditional activation of
      Notch signaling in osteocytes triggers profound bone formation, mainly due to
      increased mineralization, which rescues both age-associated and ovariectomy
      induced bone loss and promotes bone healing following osteotomy. In parallel,
      mice rendered haploinsufficient in gamma-secretase presenilin-1 (Psen1), which
      inhibits downstream Notch activation, display almost-absent terminal osteoblast
      differentiation. Consistent with this finding, pharmacologic or genetic
      disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest
      that stimulation of Notch signaling in osteocytes initiates a profound,
      therapeutically relevant, anabolic response. 

PMID- 27036010
TI  - Correction to Supporting Information for Wang et al., TLR4/MD-2 activation by a
      synthetic agonist with no similarity to LPS.

PMID- 27036008
TI  - Reporter nanoparticle that monitors its anticancer efficacy in real time.
AB  - The ability to monitor the efficacy of an anticancer treatment in real time can
      have a critical effect on the outcome. Currently, clinical readouts of efficacy
      rely on indirect or anatomic measurements, which occur over prolonged time scales
      postchemotherapy or postimmunotherapy and may not be concordant with the actual
      effect. Here we describe the biology-inspired engineering of a simple 2-in-1
      reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy
      payload to the tumor but also reports back on the efficacy in real time. The
      reporter nanoparticles are engineered from a novel two-staged stimuli-responsive
      polymeric material with an optimal ratio of an enzyme-cleavable drug or
      immunotherapy (effector elements) and a drug function-activatable reporter
      element. The spatiotemporally constrained delivery of the effector and the
      reporter elements in a single nanoparticle produces maximum signal enhancement
      due to the availability of the reporter element in the same cell as the drug,
      thereby effectively capturing the temporal apoptosis process. Using chemotherapy
      sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter
      nanoparticles can provide a real-time noninvasive readout of tumor response to
      chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune
      checkpoint inhibition in melanoma. The self-reporting capability, for the first
      time to our knowledge, captures an anticancer nanoparticle in action in vivo. 

PMID- 27036011
TI  - Correction for Patterson et al., A respiratory chain controlled signal
      transduction cascade in the mitochondrial intermembrane space mediates hydrogen
      peroxide signaling.

PMID- 27036009
TI  - Myofibroblasts are distinguished from activated skin fibroblasts by the
      expression of AOC3 and other associated markers.
AB  - Pericryptal myofibroblasts in the colon and rectum play an important role in
      regulating the normal colorectal stem cell niche and facilitating tumor
      progression. Myofibroblasts previously have been distinguished from normal
      fibroblasts mostly by the expression of alpha smooth muscle actin (alphaSMA). We
      now have identified AOC3 (amine oxidase, copper containing 3), a surface
      monoamine oxidase, as a new marker of myofibroblasts by showing that it is the
      target protein of the myofibroblast-reacting mAb PR2D3. The normal and tumor
      tissue distribution and the cell line reactivity of AOC3 match that expected for
      myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to
      digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used
      for FACS sorting of myofibroblasts obtained by nonenzymatic procedures. Whole
      genome microarray mRNA-expression profiles of myofibroblasts and skin fibroblasts
      revealed four additional genes that are significantly differentially expressed in
      these two cell types: NKX2-3 and LRRC17 in myofibroblasts and SHOX2 and TBX5 in
      skin fibroblasts. TGFbeta substantially down-regulated AOC3 expression in
      myofibroblasts but in skin fibroblasts it dramatically increased the expression
      of alphaSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of
      myofibroblast-related gene expression and increased expression of the fibroblast
      associated gene SHOX2, suggesting that NKX2-3 is a key mediator for maintaining
      myofibroblast characteristics. Our results show that colorectal myofibroblasts,
      as defined by the expression of AOC3, NKX2-3, and other markers, are a distinctly
      different cell type from TGFbeta-activated fibroblasts. 

PMID- 27036012
TI  - Correction for Gaiser et al., Cancer-associated epithelial cell adhesion molecule
      (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo.

PMID- 27036013
TI  - Correction for Fukuda et al., Redox-coupled proton transfer mechanism in nitrite
      reductase revealed by femtosecond crystallography.

PMID- 27036014
TI  - Correction for Williams, News Feature: Genetic mutations you want.

PMID- 27036016
TI  - Inhibiting cell migration and cell invasion by silencing the transcription factor
      ETS-1 in human bladder cancer.
AB  - As one of the members of the ETS gene family, the transcription factor v-ets
      avian erythroblastosis virus E26 oncogene homolog 1 (ETS-1) plays key role in the
      regulation of physiological processes in normal cells and tumors. In this study,
      we aimed to investigate the relationship between the transcription factor ETS-1
      and malignant phenotypes of bladder cancer. We demonstrated that ETS-1 was up
      regulated in human bladder cancer tissue compared to paired normal bladder
      tissue. In order to evaluate the functional role of ETS-1 in human bladder
      cancer, vectors expressing ETS-1 shRNA and ETS-1 protein were constructed in
      vitro and transfected into the human bladder cancer T24 and 5637 cells. Our
      results showed that the transcription factor ETS-1 could promote cell migration
      and cell invasion in human bladder cancer, without affecting cell proliferation
      and apoptosis. In conclusion, ETS-1 plays oncogenic roles through inducing cell
      migration and invasion in human bladder cancer, and it can be used as a
      therapeutic target for treating human bladder cancer. 

PMID- 27036017
TI  - Docosahexaenoic acid inhibits 12-O-tetradecanoylphorbol-13- acetate-induced
      fascin-1-dependent breast cancer cell migration by suppressing the PKCdelta- and
      Wnt-1/beta-catenin-mediated pathways.
AB  - Fascin-1, an actin-bundling protein, plays an important role in cancer cell
      migration and invasion; however, the underlying mechanism remains unclear. On the
      basis of a 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell migration
      model, it was shown that TPA increased fascin-1 mRNA and protein expression and
      fascin-1-dependent cell migration. TPA dose- and time-dependently increased
      PKCdelta and STAT3alpha activation and GSK3beta phosphorylation; up-regulated Wnt
      1, beta-catenin, and STAT3alpha expression; and increased the nuclear
      translocation of beta-catenin and STAT3alpha. Rottlerin, a PKCdelta inhibitor,
      abrogated the increases in STAT3alpha activation and beta-catenin and fascin-1
      expression. WP1066, a STAT3 inhibitor, suppressed TPA-induced STAT3alpha DNA
      binding activity and beta-catenin expression. Knockdown of beta-catenin
      attenuated TPA-induced fascin-1 and STAT3alpha expression as well as cell
      migration. In addition to MCF-7, migration of Hs578T breast cancer cells was
      inhibited by silencing fascin-1, beta-catenin, and STAT3alpha expression as well.
      TPA also induced Wnt-1 expression and secretion, and blocking Wnt-1 signaling
      abrogated beta-catenin induction. DHA pretreatment attenuated TPA-induced cell
      migration, PKCdelta and STAT3alpha activation, GSK3beta phosphorylation, and Wnt
      1, beta-catenin, STAT3alpha, and fascin-1 expression. Our results demonstrated
      that TPA-induced migration is likely associated with the PKCdelta and Wnt-1
      pathways, which lead to STAT3alpha activation, GSK3beta inactivation, and beta
      catenin increase and up-regulation of fascin-1 expression. Moreover, the anti
      metastatic potential of DHA is partly attributed to its suppression of TPA
      activated PKCdelta and Wnt-1 signaling. 

PMID- 27036015
TI  - The emerging role of FTY720 (Fingolimod) in cancer treatment.
AB  - FTY720 (Fingolimod) is a clinically approved immunomodulating therapy for
      multiple sclerosis that sequesters T-cells to lymph nodes through functional
      antagonism of sphingosine-1-phosphate 1 receptor. FTY720 also demonstrates a
      proven efficacy in multiple in vitro and in vivo cancer models, suggesting a
      potential therapeutic role in cancer patients. A potential anticancer mechanism
      of FTY720 is through the inhibition of sphingosine kinase 1, a proto-oncogene
      with in vitro and clinical cancer association. In addition, FTY720's anticancer
      properties may be attributable to actions on several other molecular targets.
      This study focuses on reviewing the emerging evidence regarding the anticancer
      properties and molecular targets of FTY720. While the clinical transition of
      FTY720 is currently limited by its immune suppression effects, studies aiming at
      FTY720 delivery and release together with identifying its key synergetic
      combinations and relevant patient subsets may lead to its rapid introduction into
      the clinic. 

PMID- 27036019
TI  - Transcriptional regulation of the potential tumor suppressor ABI3 gene in thyroid
      carcinomas: interplay between methylation and NKX2-1 availability.
AB  - We previously reported that ABI3 expression was decreased in thyroid cancer
      tissues and that ectopic expression of ABI3 in a follicular thyroid carcinoma
      cell line delayed cell cycle progression and inhibited cell proliferation,
      invasion, migration and tumor formation in athymic mice. These data indicated
      that ABI3 is a tumor suppressor gene; however the mechanism through which ABI3 is
      silenced in thyroid carcinomas is unknown. We here show that treatment of four
      follicular thyroid carcinoma cell lines with 5-aza-dC induced demethylation of a
      specific region of the ABI3 promoter and restored ABI3 expression. In contrast, 5
      aza-dC treatment did not restore ABI3 expression in a non-thyroid cell line,
      suggesting a tissue-specific regulation. We additionally show that 8 CpG sites
      located within the ABI3 promoter are hypermethylated in most thyroid carcinoma
      samples and the degree of methylation correlated with ABI3 expression. Narrowing
      the region to specific CpG sites, the CpG4-6 sites showed the largest difference
      between benign and malignant lesions. In silico analysis revealed that these CpG
      sites flank a canonical binding site for NKX2-1, a thyroid specific
      transcriptional factor. Analysis of thyroid samples shows a correlation between
      NKX2-1 and ABI3 expression. In vitro assays demonstrate that NKX2-1 was required
      for ABI3 expression. Luciferase assay further confirmed the promoter activity of
      this region, which was increased when the cells were co-transfected with NKX2-1.
      Our study shows that the transcriptional silencing of ABI3 in cancer cells occurs
      via methylation and uncovered a previously unrecognized role for NKX2-1 in the
      regulation of ABI3. 

PMID- 27036018
TI  - miR-509-3p is clinically significant and strongly attenuates cellular migration
      and multi-cellular spheroids in ovarian cancer.
AB  - Ovarian cancer presents as an aggressive, advanced stage cancer with widespread
      metastases that depend primarily on multicellular spheroids in the peritoneal
      fluid. To identify new druggable pathways related to metastatic progression and
      spheroid formation, we integrated microRNA and mRNA sequencing data from 293
      tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified
      miR-509-3p as a clinically significant microRNA that is more abundant in patients
      with favorable survival in both the TCGA cohort (P = 2.3E-3), and, by in situ
      hybridization (ISH), in an independent cohort of 157 tumors (P < 1.0E-3). We
      found that miR-509-3p attenuated migration and disrupted multi-cellular spheroids
      in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with
      disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti
      correlated predicted targets were enriched in components of the extracellular
      matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p
      target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated
      migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but
      not in the other cell lines, in which levels of this protein were moderate to
      low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target
      in cancers with high YAP1, and we propose that therapeutically targeting the miR
      509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid
      formation, and so inhibit metastasis in epithelial ovarian cancer and potentially
      in other cancers. 

PMID- 27036020
TI  - A high-content EMT screen identifies multiple receptor tyrosine kinase inhibitors
      with activity on TGFbeta receptor.
AB  - An epithelial to mesenchymal transition (EMT) enables epithelial tumor cells to
      break out of the primary tumor mass and to metastasize. Understanding the
      molecular mechanisms driving EMT in more detail will provide important tools to
      interfere with the metastatic process. To identify pharmacological modulators and
      druggable targets of EMT, we have established a novel multi-parameter, high
      content, microscopy-based assay and screened chemical compounds with activities
      against known targets. Out of 3423 compounds, we have identified 19 drugs that
      block transforming growth factor beta (TGFbeta)-induced EMT in normal murine
      mammary gland epithelial cells (NMuMG). The active compounds include inhibitors
      against TGFbeta receptors (TGFBR), Rho-associated protein kinases (ROCK), myosin
      II, SRC kinase and uridine analogues. Among the EMT-repressing compounds, we
      identified a group of inhibitors targeting multiple receptor tyrosine kinases,
      and biochemical profiling of these multi-kinase inhibitors reveals TGFBR as a
      thus far unknown target of their inhibitory spectrum. These findings demonstrate
      the feasibility of a multi-parameter, high-content microscopy screen to identify
      modulators and druggable targets of EMT. Moreover, the newly discovered "off
      target" effects of several receptor tyrosine kinase inhibitors have important
      consequences for in vitro and in vivo studies and might beneficially contribute
      to the therapeutic effects observed in vivo. 

PMID- 27036021
TI  - miR-340 and ZEB1 negative feedback loop regulates TGF-beta- mediated breast
      cancer progression.
AB  - MicroRNAs act as key regulators in carcinogenesis and progression in various
      cancers. In present study, we explored the role of miR-340 in the breast cancer
      progression. Our results showed that overexpression of miR-340 inhibits breast
      cancer cell proliferation and invasion, whereas depletion of miR-340 promotes
      breast cancer progression. Molecularly, ZEB1 was identified as a target gene of
      miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the
      3'-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340
      expression. The negative feedback loop regulated TGF-beta-mediated breast cancer
      progression. In conclusion, our data suggested that miR-340 acted as a tumor
      suppressor in breast cancer progression. 

PMID- 27036022
TI  - The phosphatase of regenerating liver-3 (PRL-3) is important for IL-6-mediated
      survival of myeloma cells.
AB  - Multiple myeloma (MM) is a neoplastic proliferation of bone marrow plasma cells.
      PRL-3 is a phosphatase induced by interleukin (IL)-6 and other growth factors in
      MM cells and promotes MM-cell migration. PRL-3 has also been identified as a
      marker gene for a subgroup of patients with MM. In this study we found that
      forced expression of PRL-3 in the MM cell line INA-6 led to increased survival of
      cells that were depleted of IL-6. It also caused redistribution of cells in cell
      cycle, with an increased number of cells in G2M-phase. Furthermore, forced PRL-3
      expression significantly increased phosphorylation of Signal transducer and
      activator of transcription (STAT) 3 both in the presence and the absence of IL-6.
      Knockdown of PRL-3 with shRNA reduced survival in MM cell line INA-6. A
      pharmacological inhibitor of PRL-3 reduced survival in the MM cell lines INA-6,
      ANBL-6, IH-1, OH-2 and RPMI8226. The inhibitor also reduced survival in 9 of 9
      consecutive samples of purified primary myeloma cells. Treatment with the
      inhibitor down-regulated the anti-apoptotic protein Mcl-1 and led to activation
      of the intrinsic apoptotic pathway. Inhibition of PRL-3 also reduced IL-6-induced
      phosphorylation of STAT3. In conclusion, our study shows that PRL-3 is an
      important mediator of growth factor signaling in MM cells and hence possibly a
      good target for treatment of MM. 

PMID- 27036023
TI  - Smurf1 regulation of DAB2IP controls cell proliferation and migration.
AB  - Tumor cell proliferation, survival and migration are regulated by the deletion of
      ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting protein (DAB2IP),
      a tumor suppressor that serves as a scaffold protein for H-Ras and TRAF2.
      Importantly, the oncogenic histone methyl-transferase EZH2 epigenetically down
      regulates DAB2IP in a variety of tumors. Recently, we demonstrated that DAB2IP is
      negatively regulated by Akt-dependent phosphorylation and SCFFbw7-mediated
      degradation. Here, we further identify the oncoprotein Smurf1, an E3-ubiquitin
      ligase, as a novel negative regulator of DAB2IP. Smurf1-mediated cellular
      proliferation and migration are largely dependent on the presence of DAB2IP,
      suggesting that DAB2IP is a key effector molecule of Smurf1 oncogenic function.
      Additionally, we identify that similar to DAB2IP, Smurf1 is also a target of
      phosphorylation by both Akt1 and Akt2 kinases, which enhances Smurf1 abundance,
      leading to a reduction in DAB2IP. Given the role of DAB2IP in tumorigenesis and
      metastasis, our data identify Smurf1 as an upstream oncogenic factor that
      negatively regulates DAB2IP to govern aberrant cell growth and migration. 

PMID- 27036024
TI  - Pre-diagnostic leukocyte mitochondrial DNA copy number and risk of lung cancer.
AB  - We prospectively investigated the relationship between mtCN and the risk of lung
      cancer in 463 case-control pairs from two prospective cohort studies, the Nurses'
      Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The
      adjusted least-squares means of log-transformed mtCN (log_mtCN) by smoking status
      were estimated by generalized linear models. Multivariable conditional logistic
      regression model adjusting for confounders was used to obtain the odds ratios
      (ORs) and 95% confidence intervals (CIs) for the association between log_mtCN and
      lung cancer risk. The adjusted least-squares mean of log_mtCN in heavy smokers
      was significantly lower than that in never smokers (P = 0.05). Compared to the
      high log_mtCN group, the risk of lung cancer was 1.29 (95% CI = 0.89-1.87) for
      the median group, and 1.11 (95% CI = 0.75-1.64) for the low group. Among current
      smokers, compared to participants with high levels of log_mtCN, those with median
      levels had a significantly higher risk of lung cancer (OR = 2.09; 95% CI = 1.12
      3.90), but not those with low levels (OR = 1.37; 95% CI = 0.75-2.48). Further
      studies are warranted to confirm these findings. 

PMID- 27036025
TI  - Identification of a three-miRNA signature as a blood-borne diagnostic marker for
      early diagnosis of lung adenocarcinoma.
AB  - BACKGROUND: The subtypes of NSCLC have unique characteristics of pathogenic
      mechanism and responses to targeted therapies. Thus, non-invasive markers for
      diagnosis of different subtypes of NSCLC at early stage are needed. RESULTS:
      Based on the results from the screening and validation process, 3 miRNAs (miR
      532, miR-628-3p and miR-425-3p) were found to display significantly different
      expression levels in early-stage lung adenocarcinoma, as compared to those in
      healthy controls. ROC analysis showed that the miRNA-based biomarker could
      distinguish lung adenocarcinoma from healthy controls with high AUC (0.974),
      sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs
      could also distinguish lung adenocarcinoma from lung benigh diseases and other
      subtypes of lung cancer. METHODS: Two hundreds and one early-stage lung
      adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy
      controls were recruited to this study. We screened the differentially expressed
      plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT
      PCR validation. A risk score model was established to evaluate the diagnostic
      value of the plasma miRNA profiling system. CONCLUSIONS: Taken together, these
      findings suggest that the 3 miRNA-based biomarker might serve as a novel non
      invasive approach for diagnosis of early-stage lung adenocarcinoma.

PMID- 27036026
TI  - Glucocorticoid receptor beta increases migration of human bladder cancer cells.
AB  - Bladder cancer is observed worldwide having been associated with a host of
      environmental and lifestyle risk factors. Recent investigations on anti
      inflammatory glucocorticoid signaling point to a pathway that may impact bladder
      cancer. Here we show an inverse effect on the glucocorticoid receptor (GR)
      isoform signaling that may lead to bladder cancer. We found similar GRalpha
      expression levels in the transitional uroepithelial cancer cell lines T24 and
      UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased
      expression of GRbeta compared to UMUC-3, which also correlated with higher
      migration rates. Knockdown of GRbeta in the T24 cells resulted in a decreased
      migration rate. Mutational analysis of the 3' untranslated region (UTR) of human
      GRbeta revealed that miR144 might positively regulate expression. Indeed,
      overexpression of miR144 increased GRbeta by 3.8 fold. In addition, miR144 and
      GRbeta were upregulated during migration. We used a peptide nucleic acid
      conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for
      miR144 in the 3'UTR of GRbeta. Sweet-P effectively prevented miR144 actions and
      decreased GRbeta expression, as well as the migration of the T24 human bladder
      cancer cells. Therefore, GRbeta may have a significant role in bladder cancer,
      and possibly serve as a therapeutic target for the disease. 

PMID- 27036027
TI  - Supra-complete surgery via dual intraoperative visualization approach (DiVA)
      prolongs patient survival in glioblastoma.
AB  - Safe and complete resection represents the first step in the treatment of
      glioblastomas and is mandatory in increasing the effectiveness of adjuvant
      therapy to prolong overall survival. With gross total resection currently limited
      in extent to MRI contrast enhancing areas, the extent to which supra-complete
      resection beyond obvious contrast enhancement could have impact on overall
      survival remains unclear. DiVA (dual intraoperative visualization approach)
      redefines gross total resection as currently accepted by enabling for the first
      time supra-complete surgery without compromising patient safety. This approach
      exploits the advantages of two already accepted surgical techniques combining
      intraoperative MRI with integrated functional neuronavigation and 5-ALA by
      integrating them into a single surgical approach. We investigated whether this
      technique has impact on overall outcome in GBM patients. 105 patients with GBM
      were included. We achieved complete resection with intraoperative MRI alone
      according to current best-practice in glioma surgery in 75 patients. 30 patients
      received surgery with supra-complete resection. The control arm showed a median
      life expectancy of 14 months, reflecting current standards-of-care and outcome.
      In contrast, patients receiving supra-complete surgery displayed significant
      increase in median survival time to 18.5 months with overall survival time
      correlating directly with extent of supra-complete resection. This extension of
      overall survival did not come at the cost of neurological deterioration. We show
      for the first time that supra-complete glioma surgery leads to significant
      prolongation of overall survival time in GBM patients. 

PMID- 27036028
TI  - Systematic discovery of drug action mechanisms by an integrated chemical genomics
      approach: identification of functional disparities between azacytidine and
      decitabine.
AB  - Polypharmacology (the ability of a drug to affect more than one molecular target)
      is considered a basic property of many therapeutic small molecules. Herein, we
      used a chemical genomics approach to systematically analyze polypharmacology by
      integrating several analytical tools, including the LINCS (Library of Integrated
      Cellular Signatures), STITCH (Search Tool for Interactions of Chemicals), and
      WebGestalt (WEB-based GEne SeT AnaLysis Toolkit). We applied this approach to
      identify functional disparities between two cytidine nucleoside analogs:
      azacytidine (AZA) and decitabine (DAC). AZA and DAC are structurally and
      mechanistically similar DNA-hypomethylating agents. However, their metabolism and
      destinations in cells are distinct. Due to their differential incorporation into
      RNA or DNA, functional disparities between AZA and DAC are expected. Indeed,
      different cytotoxicities of AZA and DAC toward human colorectal cancer cell lines
      were observed, in which cells were more sensitive to AZA. Based on a
      polypharmacological analysis, we found that AZA transiently blocked protein
      synthesis and induced an acute apoptotic response that was antagonized by
      concurrently induced cytoprotective autophagy. In contrast, DAC caused cell cycle
      arrest at the G2/M phase associated with p53 induction. Therefore, our study
      discriminated functional disparities between AZA and DAC, and also demonstrated
      the value of this chemical genomics approach that can be applied to discover
      novel drug action mechanisms. 

PMID- 27036029
TI  - Acquired resistance to the second-generation androgen receptor antagonist
      enzalutamide in castration-resistant prostate cancer.
AB  - Enzalutamide (MDV3100) is a second generation Androgen Receptor (AR) antagonist
      with proven efficacy in the treatment of castration resistant prostate cancer
      (CRPC). The majority of treated patients, however, develop resistance and disease
      progression and there is a critical need to identify novel targetable pathways
      mediating resistance. The purpose of this study was to develop and extensively
      characterize a series of enzalutamide-resistant prostate cancer cell lines. Four
      genetically distinct AR-positive and AR-pathway dependent prostate cancer cell
      lines (CWR-R1, LAPC-4, LNCaP, VCaP) were made resistant to enzalutamide by long
      term culture (> 6 months) in enzalutamide. Extensive characterization of these
      lines documented divergent in vitro growth characteristics and AR pathway
      modulation. Enzalutamide-resistant LNCaP and CWR-R1 cells, but not LAPC-4 and
      VCAP cells, demonstrated increased castration-resistant and metastatic growth in
      vivo. Global gene expression analyses between short-term enzalutamide treated vs.
      enzalutamide-resistant cells identified both AR pathway and non-AR pathway
      associated changes that were restored upon acquisition of enzalutamide
      resistance. Further analyses revealed very few common gene expression changes
      between the four resistant cell lines. Thus, while AR-mediated pathways
      contribute in part to enzalutamide resistance, an unbiased approach across
      several cell lines demonstrates a greater contribution toward resistance via
      pleiotropic, non-AR mediated mechanisms. 

PMID- 27036031
TI  - Effect of IL-7 and IL-15 on T cell phenotype in myelodysplastic syndromes.
AB  - Aberrant T cell phenotype is one of the characteristics of myelodysplastic
      syndromes (MDS). In this study, we detected an increased concentration of IL-15
      in the plasma of MDS patients (n = 20) compared with that in the plasma of
      healthy controls (n = 20). In MDS patients, reduced naive CD4+ and CD8+ T cells
      [16.11 +/- 6.56 vs. 24.11 +/- 7.18 for CD4+ T cells (p < 0.001) and 13.15 +/-
      5.67 vs. 23.51 +/- 6.25 for CD8+ T cells (p < 0.001)] were observed. The reduced
      naive and increased effector memory T cells were significantly correlated with IL
      15 plasma level. Then, the effect of IL-15 and IL-7 was tested in vitro.
      Peripheral blood mononuclear cells from MDS were treated for 15 days with IL-15.
      This treatment significantly decreased naive CD4+ (p < 0.001) and CD8+ (p <
      0.001) T cells and correspondingly increased terminal memory CD4+ and CD8+ T
      cells (p < 0.001). Treatment with IL-7 increased naive CD4+ (p < 0.05) and CD8+
      (p < 0.001) T cells. Our results indicated that exposure to high levels of IL-15
      may be involved in the T cell phenotype conversion observed in MDS. IL-7 may be
      one of the promising therapeutic candidates for recovering the effector immune
      compartment in MDS patients. 

PMID- 27036030
TI  - MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.
AB  - In this study, we performed microRNA (miRNA) expression profiling on a large
      series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC).
      More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor
      tissues, partially overlapping with results of previous studies. We focused our
      attention on the strongest up-regulated miRNA in MTC samples, miR-375, the
      deregulation of which has been previously observed in a variety of human
      malignancies including MTC. We identified miR-375 targets by combining gene
      expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1)
      cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic,
      respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell
      Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR
      375 target, which we validated by immunoblotting and immunohistochemistry of non
      tumor and pathological thyroid tissue. Furthermore, we observed that miR-375
      overexpression was associated with decreased cell proliferation and
      synergistically increased sensitivity to vandetanib, the clinically relevant
      treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and
      decreased AKT phosphorylation, affecting both cell proliferation and viability.
      We confirmed these results through SEC23A direct silencing in combination with
      vandetanib, highlighting the importance of SEC23A in the miR-375-associated
      increased sensitivity to vandetanib.Since the combination of increased expression
      of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib,
      we question if the expression levels of miR-375 and SEC23A should be evaluated as
      an indicator of eligibility for treatment of MTC patients with vandetanib. 

PMID- 27036032
TI  - Low disabled-2 expression promotes tumor progression and determines poor survival
      and high recurrence of esophageal squamous cell carcinoma.
AB  - Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and
      high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a
      crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated
      whether low DAB2 expression in ESCCs could lead into tumor progression and poor
      prognosis. Our results found patients with low-DAB2 expression ESCCs had
      significantly larger tumor size, deeper tumor invasion depth, lymph node
      metastasis, worse survival, and higher recurrence rate (P<0.05). The Cox
      regression model revealed low-DAB2 expression was an independent factor of poor
      survival (P<0.05), and also of tumor recurrence with the predictive performance
      superior to clinical TNM stage (P<0.05). Low-DAB2 cancer cells, validated by DAB2
      knockdown or over-expression, had higher phosphorylated ERK and migration
      abilities, which could be suppressed by ERK inhibitor treatment. TGF-beta-induced
      epithelial-to-mesenchymal transition (EMT) only existed in the high-DAB2 cells,
      and related to worse prognosis of high-DAB2 ESCCs (P<0.05). In conclusion, DAB2
      can suppress the ERK signaling, but correlate to have TGF-beta-induced EMT in
      ESCCs. DAB2 expression could be a biomarker to identify patients with worse
      survival and high recurrence. Our data suggest DAB2 expression can stratify
      patients in need of aggressive surveillance and with possible benefit from anti
      ERK or anti-TGF-beta therapies.

PMID- 27036033
TI  - N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma
      cell line and sensitizes it to chemotherapeutic agents.
AB  - Neuroblastoma is the most commonly extra-cranial solid tumor of childhood
      frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate
      (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the
      most abundant metabolites present in the central nervous system (CNS) and appears
      to be involved in many CNS disorders. The functional significance of the high NAA
      concentration in the brain remains uncertain, but it confers to NAA a unique
      clinical significance exploited in magnetic resonance spectroscopy. In the
      current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line
      with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This
      effect is partly due to enhanced apoptosis, shown by decrease of the anti
      apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle
      progression, linked to enhanced expression of the cyclin-inhibitors p53,
      p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited
      morphological changes accompanied with increase of the neurogenic markers TH and
      MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184.
      Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic
      effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our
      knowledge, this is the first study demonstrating the neuronal differentiating
      effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or
      adjuvant compound in chemotherapeutic treatment. 

PMID- 27036034
TI  - High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with
      increased risk of graft-versus-host disease without beneficial effect on disease
      control after reduced-intensity conditioning allogeneic transplantation from
      matched unrelated donors for acute myeloid leukemia - an analysis from the Acute
      Leukemia Working Party of the European Society for Blood and Marrow
      Transplantation.
AB  - Inconsistent results have been reported regarding the influence of graft
      composition on the incidence of graft versus host disease (GVHD), disease control
      and survival after reduced-intensity conditioning (RIC) allogeneic peripheral
      blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least
      in part explained by the differences in disease categories, disease status at
      transplant, donor type and conditioning. The current retrospective EBMT registry
      study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of
      RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first
      complete remission, allografted from HLA-matched unrelated donors (10 of 10
      match). We included 203 adults. In univariate analysis, patients transplanted
      with the highest CD3+ and CD34+ doses (above the third quartile cut-off point
      values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased
      incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P
      = .02, respectively). There was no association between cellular composition of
      grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD
      and survival. Neither engraftment itself nor the kinetics of engraftment were
      affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were
      the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45
      9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results
      suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the
      cell dose infused may help in reducing severe acute GVHD risk without negative
      impact on the other transplantation outcomes. 

PMID- 27036035
TI  - Distinctly altered gut microbiota in the progression of liver disease.
AB  - Recent studies underscore important roles of intestinal microbiota and the
      bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver
      disease. However, how gut microbiota alters in response to the development of
      steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and
      hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut
      microbial changes over liver disease progression using a streptozotocin-high fat
      diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to
      human liver disease. The fecal microbiota at various liver pathological stages
      was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial
      least squares-discriminant analysis showed significant structural alterations in
      gut microbiota during the development of liver disease. Co-abundance network
      analysis highlighted relationships between genera. Spearman correlation analysis
      revealed that the bacterial species, Atopobium spp., Bacteroides spp.,
      Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis,
      Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly
      increased in model mice, were positively correlated with LPS levels and
      pathophysiological features. Taken together, the results showed that the gut
      microbiota was altered significantly in the progression of liver disease. The
      connection between the gut microbial ecology and the liver pathology may
      represent potential targets for the prevention and treatment of chronic liver
      disease and HCC. 

PMID- 27036036
TI  - Marital status independently predicts pancreatic cancer survival in patients
      treated with surgical resection: an analysis of the SEER database.
AB  - Marital status is an independent prognostic factor for survival in several
      cancers. To determine if that is also true for pancreatic cancer after surgical
      treatment, we examined 13,370 cases of pancreatic cancer reported to the
      Surveillance, Epidemiology, and End Results (SEER) database between 1988 and
      2012. We found that patients who were widowed at the time of diagnosis were more
      likely to be female, a high percentage were elderly, a high ratio were diagnosed
      in early years, and a high proportion of tumors were located at the head of the
      pancreas (P < 0.05). Marital status was confirmed to be an independent prognostic
      factor in both univariate and multivariate analyses (P < 0.05). In those with
      localized disease, 5-year pancreatic cancer cause-specific survival was 6.5%
      lower in widowed patients than married ones (38.6% vs. 32.1%), though this
      difference was not significant in a multivariate analysis (P = 0.084). In those
      with regional disease or distant metastasis, univariate and multivariate analyses
      indicated marital status to be an independent prognostic factor (P < 0.05). Thus
      marital status is an important prognostic factor in pancreatic cancer, and
      widowed patients are at greater risk of death than others. 

PMID- 27036037
TI  - Age related increase in mTOR activity contributes to the pathological changes in
      ovarian surface epithelium.
AB  - Ovarian cancer is a disease of older women. However, the molecular mechanisms of
      ovarian aging and their contribution to the pathogenesis of ovarian cancer are
      currently unclear. mTOR signalling is a major regulator of aging as suppression
      of this pathway extends lifespan in model organisms. Overactive mTOR signalling
      is present in up to 80% of ovarian cancer samples and is associated with poor
      prognosis. This study examined the role of mTOR signalling in age-associated
      changes in ovarian surface epithelium (OSE). Histological examination of ovaries
      from both aged mice and women revealed OSE cell hyperplasia, papillary growth and
      inclusion cysts. These pathological lesions expressed bonafide markers of ovarian
      cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated
      mTOR signalling. To understand whether overactive mTOR signalling is responsible
      for the development of these pathological changes, we analysed ovaries of the
      Pten trangenic mice and found significant reduction in OSE lesions compared to
      controls. Furthermore, pharmacological suppression of mTOR signalling
      significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR
      inhibitors reduced human ovarian cancer cell viability, proliferation and colony
      forming ability. Collectively, we have established the role of mTOR signalling in
      age-related OSE pathologies and initiation of ovarian cancer. 

PMID- 27036038
TI  - hsa-miR-9 controls the mobility behavior of glioblastoma cells via regulation of
      MAPK14 signaling elements.
AB  - BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and lethal primary
      tumor of the brain. GBM is associated with one of the worst 5-year survival rates
      among all human cancers, despite much effort in different modes of treatment.
      RESULTS: Here, we demonstrate specific GBM cancer phenotypes that are governed by
      modifications to the MAPAKAP network. We then demonstrate a novel regulation mode
      by which a set of five key factors of the MAPKAP pathway are regulated by the
      same microRNA, hsa-miR-9.We demonstrate that hsa-miR-9 overexpression leads to
      MAPKAP signaling inhibition, partially by interfering with the MAPK14/MAPKAP3
      complex. Further, hsa-miR-9 overexpression initiates re-arrangement of actin
      filaments, which leads us to hypothesize a mechanism for the observed phenotypic
      shift. CONCLUSION: The work presented here exposes novel microRNA features and
      situates hsa-miR-9 as a therapeutic target, which governs metastasis and thus
      determines prognosis in GBM through MAPKAP signaling.

PMID- 27036039
TI  - E2F1-induced upregulation of long noncoding RNA LINC00668 predicts a poor
      prognosis of gastric cancer and promotes cell proliferation through
      epigenetically silencing of CKIs.
AB  - Recently, long noncoding RNAs (lncRNAs) have been shown to have important
      regulatory roles in human cancer biology. By utilizing publicly available lncRNAs
      expression profiling data and integrating analyses, we screened out LINC00668,
      whose expression is significantly increased and correlated with outcomes in
      gastric cancer (GC). Further experiments revealed that LINC00668 knockdown
      significantly repressed proliferation, both in vitro and in vivo. Mechanistic
      investigations showed that LINC00668 was a direct transcriptional target of E2F
      transcription factor 1 (E2F1). We further demonstrated that LINC00668 was
      associated with PRC2 and that this association was required for epigenetic
      repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15,
      p16, p21, p27 and p57, thus contributing to the regulation of the gastric cancer
      cell cycle. Our results suggest that E2F1-activated LINC00668, as a cell cycle
      regulator, enriches the mechanistic link between lncRNA and the E2F1-mediated
      cell cycle regulation pathway and may serve as a candidate prognostic biomarker
      and target for new therapies in human gastric cancer. 

PMID- 27036040
TI  - The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein
      receptor in malignancy of human endometrial cancer cells.
AB  - Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a novel
      molecular constituent of tricellular contacts that have a barrier function for
      the cellular sheet. LSR recruits tricellulin (TRIC), which is the first molecular
      component of tricellular tight junctions. Knockdown of LSR increases cell
      motility and invasion of certain cancer cells. However, the behavior and the
      roles of LSR in endometrial cancer remain unknown. In the present study, we
      investigated the behavior and roles of LSR in normal and endometrial cancer cells
      in vivo and in vitro. In endometriosis and endometrial cancer, LSR was observed
      not only in the subapical region but also throughout the lateral region as well
      as in normal endometrial epithelial cells in the secretory phase, and LSR in the
      cancer was reduced in correlation with the malignancy. Knockdown of LSR by the
      siRNA in cells of the endometrial cancer cell line Sawano, induced cell
      migration, invasion and proliferation, while TRIC relocalized from the
      tricellular region to the bicellular region at the membrane. In Sawano cells and
      normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced
      by adiponectin and the drugs for type 2 diabetes metformin and berberine were
      observed via distinct signaling pathways including JAK2/STAT. In Sawano cells,
      metformin and berberine prevented cell migration and invasion induced by
      downregulation of LSR by the siRNA and leptin treatment. The dissection of the
      mechanism in the downregulation of endometrial LSR during obesity is important in
      developing new diagnostic and therapy for endometrial cancer. 

PMID- 27036041
TI  - miR-590 promotes cell proliferation and invasion in T-cell acute lymphoblastic
      leukaemia by inhibiting RB1.
AB  - MicroRNAs play important roles in the pathogenesis of cancers by inhibiting gene
      expression at posttranscriptional level. Here, we identified that miR-590 and its
      predicted target gene RB1 are differentially expressed in T-cell acute
      lymphoblastic leukaemia (T-ALL). The correlation between miR-590 and RB1 was
      further confirmed in 395 T-ALL patients. In T-ALL cell lines, miR-590 promoted
      the cell proliferation by increasing G1/S transition. Moreover, migration and
      invasion assay showed that miR-590 promotes the migration and invasion of T-ALL
      cells by increasing E-cadherin and inhibiting MMP-9. Luciferase assays confirmed
      that miR-590 directly binds to the 3'untranslated region of RB1, and western
      blotting showed that miR-590 suppresses the expression of RB1 at the protein
      levels. This study indicated that miR-590 inhibits RB1 and promotes proliferation
      and invasion of T-ALL cells. Thus, miR-590 may represent a potential therapeutic
      target for T-ALL intervention.

PMID- 27036042
TI  - Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met
      oncogene addiction in cancer cells.
AB  - As an environmental poison, arsenic is responsible for many cancer deaths.
      Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to
      treat refractory acute promyelocytic leukemia (APL) and is intensively
      investigated for treatment of other cancer types. Noteworthy, cancer therapy is
      frequently hampered by drug resistance, which is also often associated with
      enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected
      cancer cells (A2780ATO) for the mechanisms underlying their enhanced
      tumorigenicity and aggressiveness. These cells were characterized by enhanced
      proliferation and spheroid growth as well as increased tumorigenicity of
      xenografts in SCID mice. Noteworthy, subsequent studies revealed that
      overexpression of Met receptor was the underlying oncogenic driver of these
      effects, as A2780ATO cells were characterized by collateral sensitivity against
      Met inhibitors. This finding was also confirmed by array comparative genomic
      hybridization (array CGH) and whole genome gene expression arrays, which revealed
      that Met overexpression by chronic ATO exposure was based on the transcriptional
      regulation via activation of AP-1. Finally, it was shown that treatment with the
      Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in
      vivo, indicating that targeting of Met presents a promising strategy for the
      treatment of Met-overexpressing tumors after either arsenic exposure or failure
      to ATO treatment. 

PMID- 27036043
TI  - Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis
      and review.
AB  - The PET Response Criteria in Solid Tumors (PERCIST) is a new method for the
      quantitative assessment of metabolic changes in solid tumors. The assessments of
      tumor response between the RECIST and PERCIST have shown considerable difference
      in several studies. This pooled study was conducted to compare tumor response
      according to the two criteria in patients with solid tumors. We surveyed MEDLINE,
      EMBASE and PUBMED for articles with terms of the RECIST or PERCIST from 2009 and
      January 2016. There were six articles comparing the RECIST and PERCIST. A total
      of 268 patients were recruited; 81 with colorectal cancer, 60 with lung cancer,
      48 with esophageal cancer, 28 with breast cancer, 14 with basal cell carcinoma,
      12 with stomach cancer, 10 with head and neck cancer, and 16 with other rare
      cancers. The agreement of tumor response between the RECIST and PERCIST was
      moderate (k = 0.590). Of 268 patients, 101 (37.7%) showed discordance in the
      tumor responses between two criteria. When adopting the PERCIST, tumor response
      was upgraded in 85 patients and downgraded in 16. The estimated overall response
      rates were significantly different between two criteria (35.1% by RECIST vs.
      54.1% by PERCIST, P < 0.0001). In conclusion, this pooled analysis demonstrates
      that the concordance of tumor responses between the RECIST and PERCIST criteria
      is not excellent. The PERCIST might be more suitable for assessing tumor response
      than the RECIST criteria. 

PMID- 27036044
TI  - Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck
      squamous cell carcinoma.
AB  - Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is
      a tight junction molecule associated with epithelial and endothelial barrier
      function. Overexpression of JAM-A is also closely associated with invasion and
      metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer.
      However, little is known about the mechanism in overexpression of JAM-A in head
      and neck squamous cell carcinoma (HNSCC). In the present study, we found high
      expression of JAM-A at the protein and mRNA levels in HNSCC tissues, including
      those of the oropharynx, larynx, and hypopharynx, together with high protein
      expression of beta-catenin, p63, DeltaNp63 and GATA-3. Furthermore, in ELISA, a
      significant increase of soluble JAM-A in the sera of HNSCC patients was observed
      compared to healthy subjects. Knockdown of JAM-A by siRNA inhibited cell
      proliferation, invasion and migration in the HNSCC cell line Detroit562 in vitro.
      JAM-A expression in Detroit562 was increased via a distinct signal transduction
      pathway including NF-kappaB. Expression of JAM-A, beta-catenin, p63 and DeltaNp63
      in Detroit562 was decreased under hypoxia. Knockdown of p63, DeltaNp63 or GATA-3
      by siRNAs reduced JAM-A expression in Detroit562. In primary cultured HNSCC cells
      in which CK7, p63, DeltaNp63 and GATA-3 were detected, JAM-A expression was
      decreased by knockdown of p63 or DeltaNp63. These results indicate that JAM-A is
      a biomarker of malignancy in HNSCC and that plasma soluble JAM-A may contribute
      to serum-based diagnosis of HNSCC. The mechanism of dysregulation of JAM-A via
      p63/GATA-3 is important in possible molecular targeted therapy for HNSCC. 

PMID- 27036046
TI  - Primary versus castration-resistant prostate cancer: modeling through novel
      murine prostate cancer cell lines.
AB  - Cell lines representing the progression of prostate cancer (PC) from an androgen
      dependent to an androgen-independent state are scarce. In this study, we used
      previously characterized prostate luminal epithelial cell line (Plum), under
      androgen influence, to establish cellular models of PC progression. Cells derived
      from orthotopic tumors have been isolated to develop an androgen-dependent (PLum
      AD) versus an androgen-independent (PLum-AI) model. Upon immunofluorescent, qRT
      PCR and Western blot analyses, PLum-AD cells mostly expressed prostate epithelial
      markers while PLum-AI cells expressed mesenchymal cell markers. Interestingly,
      both cell lines maintained a population of stem/progenitor cells. Furthermore,
      our data suggest that both cell lines are tumorigenic; PLum-AD resulted in an
      adenocarcinoma whereas PLum-AI resulted in a sarcomatoid carcinoma when
      transplanted subcutaneously in NOD-SCID mice. Finally, gene expression profiles
      showed enrichment in functions involved in cell migration, apoptosis, as well as
      neoplasm invasiveness and metastasis in PLum-AI cells. In conclusion, these data
      suggest that the newly isolated cell lines represent a new in vitro model of
      androgen-dependent and -independent PC. 

PMID- 27036045
TI  - Slug inhibits the proliferation and tumor formation of human cervical cancer
      cells by up-regulating the p21/p27 proteins and down-regulating the activity of
      the Wnt/beta-catenin signaling pathway via the trans-suppression Akt1/p-Akt1
      expression.
AB  - Slug (Snai2) has been demonstrated to act as an oncogene or tumor suppressor in
      different human cancers, but the function of Slug in cervical cancer remains
      poorly understood. In this study, we demonstrated that Slug could suppress the
      proliferation of cervical cancer cells in vitro and tumor formation in vivo.
      Further experiments found that Slug could trans-suppress the expression of Akt1/p
      Akt1 by binding to E-box motifs in the promoter of the Akt1 gene and then inhibit
      the cell proliferation and tumor formation of cervical cancer cells by up
      regulating p21/p27 and/or down-regulating the activity of the Wnt/beta-catenin
      signaling pathway. Therefore, Slug acts as a tumor suppressor during cervical
      carcinogenesis. 

PMID- 27036047
TI  - Period2 downregulation inhibits glioma cell apoptosis by activating the MDM2-TP53
      pathway.
AB  - The Period2 (Per2) gene is an essential component of the mammalian circadian
      clock and is strongly linked to glioma occurrence and its response to
      radiotherapy. Here, we examined the role of Per2 in the response to X-ray-induced
      DNA damage in U343 glioma cells and in a mouse cancer model. Following low dose X
      ray irradiation, we observed that lowering Per2 expression using RNAi reduces DNA
      damage and cell death in U343 cells and glioma tissue. Additionally, Per2 was
      associated with increased TP53 activity and was involved in the DNA damage during
      TP53-mediated apoptosis. These findings suggest that Per2, a core circadian gene,
      is not only a tumor suppressor gene but can also be regarded as an upstream
      regulator of TP53. It thus appears that Per2 is an important inhibitor of tumor
      growth that acts by increasing TP53 expression, DNA damage repair, and apoptosis.

PMID- 27036048
TI  - Aberrantly activated Gli2-KIF20A axis is crucial for growth of hepatocellular
      carcinoma and predicts poor prognosis.
AB  - Glioma-associated oncogene 2 (Gli2), a primary transcriptional regulator of
      Hedgehog (Hh) signaling, is essential for hepatocellular carcinoma (HCC) growth
      and survival. However, the underlying molecular mechanism and crucial downstream
      targets of Gli2 in human HCC are not fully understood. Here, we report the
      identification of kinesin family member 20A (KIF20A) as a novel downstream target
      of Gli2, which is important for HCC proliferation and tumor growth. Inhibition of
      Hh signaling leads to a remarkable decrease of KIF20A expression in HCC cells,
      whereas overexpression of Gli2 elevates KIF20A expression by activating Forkhead
      Box M1 (FoxM1)-MMB complex-mediated transcription of this kinesin gene. Gli2
      induced HCC cell growth requires enhanced expression of KIF20A, and knockdown of
      Gli2 or KIF20A represses the proliferation of HCC cells in vitro and in vivo.
      Correlated with these results, analyses of clinical HCC samples show that Gli2,
      FoxM1 and KIF20A are highly elevated in primary HCC samples and represent
      significant risk factors for HCC recurrence and survival. CONCLUSION: KIF20A is
      an important downstream target gene of Hh signaling. And, the Gli2-KIF20A axis is
      essential for the proliferation and growth of human HCC cells. Our study also
      suggests Gli2-KIF20A axis as a potential target for future therapeutic
      intervention and as an independent prognostic biomarker for HCC.

PMID- 27036050
TI  - The Blood-Brain Barrier.

PMID- 27036049
TI  - REG4 promotes peritoneal metastasis of gastric cancer through GPR37.
AB  - Being the major reason of recurrence and death after surgery, peritoneal
      metastasis of gastric cancer dooms the prognosis of advanced gastric cancer
      patients. Regenerating islet-derived family, member 4 (REG4) is believed to
      promote peritoneal metastasis, however, its mechanism is still a moot point at
      present. In the present study, we show that high expression of REG4 correlates
      with advanced stage and poor survival prognosis for gastric cancer patients. REG4
      overexpression significantly enhances peritoneal metastasis by increasing
      adhesion ability. Moreover, SP1 is proved to be a transcription factor of REG4
      and induce REG4 expression upon TGF-alpha stimulation. Also, G protein-coupled
      receptor 37 (GPR37) is identified to be in the same complex of REG4, which
      mediates REG4's signal transduction and promotes peritoneal metastasis of gastric
      cancer cell. Interestingly, we also discover a positive feedback loop triggered
      by REG4, amplifying itself through EGFR transactivation, consisting of GPR37,
      ADAM17, TGF-alpha, EGFR, SP1 and REG4. In conclusion, REG4 promotes peritoneal
      metastasis of gastric cancer through GPR37 and triggers a positive feedback loop.

PMID- 27036051
TI  - Renin-Angiotensin-Aldosterone Signaling Inhibitors-Losartan, Enalapril, and
      Cardosten-Prevent Infarction-induced Heart Failure Development in Rats.
AB  - CONTEXT: The activation of the renin-angiotensin-aldosterone system (RAAS) plays
      an important role in the pathophysiology of congestive heart failure, which is
      the reason that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
      2 receptor blockers (ARBs) have become established therapies for heart failure.
      However, it is still not known whether preventive treatment with losartan or
      enalapril can reduce symptoms of infarction-induced heart failure. Ultra-low dose
      (ULD) drug therapy is thought to exert specific activity, with a lower chance of
      side effects. OBJECTIVES * The research team had hypothesized that preventive
      treatment with inhibitors of RAAS signaling-losartan, enalapril, and a
      preparation of a ULD antibody (ie, cardosten), which target the angiotensin type
      1 (AT1) receptor-might alleviate pathological hypertrophy and/or functional
      decline in infarction-induced heart failure. METHODS: The research team treated
      male Wistar rats orally for 30 d with 20 mg/kg of losartan, 10 mg/kg enalapril, 5
      or 7.5 mL/kg of cardosten, or a control solution, started 1 d prior to permanent
      coronary occlusion. A sham-operated group functioned as a second control group.
      SETTINGS: The study was conducted at the Department of Biochemistry of the
      Faculty of Medicine at the University of Szeged in Szeged, Hungary, in
      cooperation with the Pharmahungary Group, also in Szeged, Hungary, and with OOO
      "NPF" Materia Medica Holding Ltd in Moscow, Russia. OUTCOME MEASURES: To
      determine cardiac functional parameters in vivo, the research team inserted a
      catheter into the left ventricle of the rats and measured the parameters of
      ventricular pressure, and cardiac output was determined by thermodilution.
      Morphological parameters were measured after heart isolation in transverse
      sections by a digital caliper. RESULTS: A total of 30 d after permanent coronary
      ligation, both losartan and enalapril, significantly decreased mean arterial
      blood pressure (MABP), attenuated the development of the left-ventricular
      anterior-wall and septum hypertrophy, and reduced scar thickness compared with
      the vehicle control group. The deterioration of cardiac output and the increase
      in total peripheral resistance (TPR) due to coronary ligation were significantly
      inhibited by both losartan and enalapril. The effects of cardosten were
      comparable with those of losartan and enalapril on cardiac morphology, left
      ventricular function, and TPR; however, it did not influence MABP. Moreover, in
      contrast to losartan and enalapril, cardosten did not decrease the rate of
      survival. CONCLUSIONS: The study was the first to have demonstrated that
      preventive treatment with losartan, enalapril, or cardosten can attenuate
      pathological hypertrophy in infarction-induced heart failure in rats.

PMID- 27036052
TI  - Occipitoatlantoaxial Manipulation for Immediate Increase to Cervical Rotation.
AB  - CONTEXT: The assessment of the range of motion (ROM) of the cervical spine is
      common in physical therapy practice. An ROM assessment is used as an integral
      part of a physical examination, both in symptomatic and asymptomatic populations.
      Spine manipulation has shown several benefits, including an increased range of
      passive rotation of the upper cervical spine. OBJECTIVES: The study intended to
      analyze the immediate effects of manipulation of the occipitoatlantoaxial (OAA)
      joint on the ROM of the cervical rotation and its relationship to an individual's
      most limited side on Mitchell's test. DESIGN: The study used a single-subject
      experimental design. SETTING: The study took place at Hospital Universitario
      Gaffree e Guinle in Rio de Janeiro, Brazil. PARTICIPANTS: A convenience sample of
      40 healthy participants with a limited ROM in respect to the rotation of the
      cervical spine, who were selected in the outpatient physical therapy team
      (professionals and students). INTERVENTION: The OAA joint manipulation was
      performed by an independent therapist on all participants, on the side with the
      greater ROM restriction only. OUTCOME MEASURES: Cervical rotation using a ROM
      fleximeter and the Mitchell's test was performed. RESULTS: At baseline, 25 of the
      participants (62.5%) had a reduction in movement for the right-side rotation,
      whereas 15 of the participants (37.5%) had restricted movement for left-side
      rotation. After the OAA manipulation, the ROM was increased on both sides
      independent of the side that had the most restriction to movement. The right-side
      rotation increased by 9.75 degrees , whereas the left-side rotation increased by
      8.26 degrees . Despite a bilateral ROM increase, a difference was observed in the
      magnitude of the changes between the more-restricted sides and the other sides
      when the Mitchell's tests were considered, with large clinical effects.
      CONCLUSIONS: The OAA manipulation increased the ROM for bilateral cervical
      rotation, irrespective of the side of the restriction, and the increase was more
      pronounced when considering the results of the Mitchell's test.

PMID- 27036053
TI  - Symbolic Analysis of Heart Rate Variability During Exposure to Musical Auditory
      Stimulation.
AB  - BACKGROUND: In recent years, the application of nonlinear methods for analysis of
      heart rate variability (HRV) has increased. However, studies on the influence of
      music on cardiac autonomic modulation in those circumstances are rare. OBJECTIVE:
      The research team aimed to evaluate the acute effects on HRV of selected auditory
      stimulation by 2 musical styles, measuring the results using nonlinear methods of
      analysis: Shannon entropy, symbolic analysis, and correlation-dimension analysis.
      DESIGN: Prospective control study in which the volunteers were exposed to music
      and variables were compared between control (no auditory stimulation) and during
      exposure to music. SETTING: All procedures were performed in a sound-proofed room
      at the Faculty of Science and Technology at Sao Paulo State University (UNESP),
      Sao Paulo, Brazil. PARTICIPANTS: Participants were 22 healthy female students,
      aged between 18 and 30 y. INTERVENTION: Prior to the actual intervention, the
      participants remained at rest for 20 min, and then they were exposed to one of
      the selected types of music, either classical baroque (64-84 dB) or heavy-metal
      (75-84 dB). Each musical session lasted a total of 5 min and 15 s. At a point
      occurring up to 1 wk after that day, the participants listened to the second type
      of music. The 2 types of music were delivered in a random sequence that depended
      on the group to which the participant was assigned. OUTCOME MEASURES: The study
      analyzed the following HRV indices through Shannon entropy; symbolic analysis
      0V%, 1V%, 2LV%, and 2ULV%; and correlation-dimension analysis. RESULTS: During
      exposure to auditory stimulation by heavy-metal or classical baroque music, the
      study established no statistically significant variations regarding the indices
      for the Shannon entropy; the symbolic analysis-0V%, 1V%, and 2ULV%; and the
      correlation-dimension analysis. However, during heavy-metal music, the 2LV% index
      in the symbolic analysis was reduced compared with the controls. CONCLUSIONS:
      Auditory stimulation with the heavy-metal music reduced the parasympathetic
      modulation of HRV, whereas no significant changes occurred in cardiac autonomic
      modulation during exposure to the classical music.

PMID- 27036054
TI  - Christopher W. Shade, PhD: The Vast Potential of Liposomal Delivery of
      Nutraceuticals.

PMID- 27036055
TI  - Cordyceps sinensis Oral Liquid Inhibits Damage Induced by Oxygen and Glucose
      Deprivation in SH-SY5Y Cells.
AB  - CONTEXT: Cordyceps sinensis has been used in traditional Chinese medicine for
      thousands of years. It has been demonstrated to have a variety of biological
      activities, and an extract of it has been demonstrated to possess a protective
      effect in occlusion-induced focal cerebral ischemia of the middle cerebral artery
      in rats. It could be explored as an agent for treatment of ischemic stroke, and
      the mechanisms need to be studied further. OBJECTIVE: The study intended to
      investigate the protective effects of the Cordyceps sinensis oral liquid (CSOL)
      against damage induced by oxygen and glucose deprivation (OGD) in SH-SY5Y cells.
      DESIGN * The research team designed an in vitro study. SETTING: The study
      occurred at the Naval Medical Research Institute in Shanghai, China.
      INTERVENTION: SH-SY5Y cells were exposed to CSOL in doses of 0.01, 0.03, 0.10,
      0.30, and 1.00 mg/mL, creating 5 intervention groups. The OGD condition was
      induced by transfer of the cells from high-glucose Dulbecco's Modified Eagle's
      medium (DMEM) in a box gassed with air containing 5% CO2 to glucose-free DMEM in
      a box gassed with 94% N2, 5% CO2, and 1% O2. Like the cells for the interventions
      groups, the cells for a model group were cultured with high-glucose DMEM and were
      transferred to the OGD, but they received no dose of COSL. Cells in a control
      group were cultured with high-glucose DMEM, were not transferred to the OGD
      condition, and did not receive any dose of COSL. OUTCOME MEASURES: Cell viability
      was assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) method. The apoptosis and the mitochondrial membrane potential
      (MMP) were detected by flow cytometry, and the protein expression of caspase-3
      was observed by western blot. RESULTS: After exposure to OGD, the cell viability
      of cells treated with 0.01, 0.03, 0.10, 0.30, and 1.00 mg/mL of CSOL increased in
      a dose-effect relationship. Compared with the cells in the model group, the
      treatment of CSOL at all the experimental concentrations significantly inhibited
      both the cell apoptosis (P < .01) and the capase-3 activation (P < .01). The MMP
      dissipation in the cells of the model group increased significantly compared with
      those of the control group (P < .01). The treatment with all doses of CSOL
      significantly inhibited the MMP dissipation (P < .01). CONCLUSIONS: CSOL protects
      against the damage induced by OGD through inhibiting the mitochondrial apoptosis
      pathway in SH-SY5Y cells.

PMID- 27036057
TI  - Robert Rountree, MD: Returning to Common-sense Medicine.

PMID- 27036056
TI  - Internet-based Mindfulness Meditation for Cognition and Mood in Older Adults: A
      Pilot Study.
AB  - CONTEXT: Older adults are at risk for greater chronic stress and cognitive
      decline. Training in mindfulness meditation (MM) may help reduce stress and,
      thus, cognitive decline in older adults, but little research has explored that
      hypothesis. OBJECTIVE: The current study's primary aim was to evaluate the
      feasibility and acceptability for use by older adults of the Internet Mindfulness
      Meditation Intervention (IMMI), a program that had been developed by the research
      team, as well as of an Internet-based health-and-wellness education program, the
      control. The secondary aim was to collect preliminary pre- and postintervention
      data on mood and cognitive function. DESIGN: The study was a randomized,
      controlled trial (RCT), a pilot study, with participants randomized either to the
      meditation group or the education group. SETTING: Participants obtained access to
      the programs from their homes, and the baseline and endpoint assessments occurred
      in their homes as well. PARTICIPANTS: Older adults aged 65-90 y were recruited
      from the Portland, OR, metropolitan area. Twenty-one people enrolled in the
      study. INTERVENTION: Participants in both groups took part in a 1-h online
      session each week for 6 wk, with 30 min of daily home practice. OUTCOME MEASURES:
      Feasibility and acceptability were assessed through measures of adherence to the
      protocol and a client satisfaction questionnaire. Mood and cognitive outcomes
      were also evaluated before and after the interventions. RESULTS: Sixteen
      participants completed the study, 8 in each group, and 5 dropped out, for a 76%
      completion rate. Participants' mean age was 76.2 y; 88% were Caucasian, and 50%
      were female. Acceptability was high for the interventions, based on above-average
      scores on the client satisfaction questionnaire. The IMMI participants completed
      (1) 4.25 +/- 2.4 sessions, with a range of 0-6; (2) 604 +/- 506 home-practice
      minutes, with a range 0-1432; and (3) 21.3 +/- 15.5 d of practice, with a range
      of 0-46. The education group completed (1) 4.75 +/- 1.8 sessions, with a range of
      2-6; (2) 873 +/- 395 home-practice minutes, with a range of 327-1524; and (3)
      25.6 d of practice, with a range of 11-35. The intervention and control formats
      were both feasible, and the control group was appropriate. As expected due to the
      pilot nature of the study, no differences existed between groups for the mood or
      cognitive outcomes. CONCLUSIONS: Administering interventions via the Internet to
      older adults is feasible. The 2 interventions were acceptable to participants and
      equal with regard to perceived credibility and acceptability. Future RCTs are
      planned to evaluate the clinical efficacy of the 2 interventions.

PMID- 27036061
TI  - Genotoxic sensitivity of the developing hematopoietic system.
AB  - Genotoxic sensitivity seems to vary during ontogenetic development. Animal
      studies have shown that the spontaneous mutation rate is higher during pregnancy
      and infancy than in adulthood. Human and animal studies have found higher levels
      of DNA damage and mutations induced by mutagens in fetuses/newborns than in
      adults. This greater susceptibility could be due to reduced DNA repair capacity.
      In fact, several studies indicated that some DNA repair pathways seem to be
      deficient during ontogenesis. This has been demonstrated also in murine
      hematopoietic stem cells. Genotoxicity in the hematopoietic system has been
      widely studied for several reasons: it is easy to assess, deals with populations
      cycling also in the adults and may be relevant for leukemogenesis. Reviewing the
      literature concerning the application of the micronucleus test (a validated assay
      to assess genotoxicity) in fetus/newborns and adults, we found that the former
      show almost always higher values than the latter, both in animals treated with
      genotoxic substances and in those untreated. Therefore, we draw the conclusion
      that the genotoxic sensitivity of the hematopoietic system is more pronounced
      during fetal life and decreases during ontogenic development. 

PMID- 27036062
TI  - How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA
      repair pathways.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, is an obligatory
      intracellular parasite with a digenetic life cycle. Due to the variety of host
      environments, it faces several sources of oxidative stress. In addition to
      reactive oxygen species (ROS) produced by its own metabolism, T. cruzi must deal
      with high ROS levels generated as part of the host's immune responses. Hence, the
      conclusion that T. cruzi has limited ability to deal with ROS (based on the lack
      of a few enzymes involved with oxidative stress responses) seems somewhat
      paradoxical. Actually, to withstand such variable sources of oxidative stress, T.
      cruzi has developed complex defence mechanisms. This includes ROS detoxification
      pathways that are distinct from the ones in the mammalian host, DNA repair
      pathways and specialized polymerases, which not only protect its genome from the
      resulting oxidative damage but also contribute to the generation of genetic
      diversity within the parasite population. Recent studies on T. cruzi's DNA repair
      pathways as mismatch repair (MMR) and GO system suggested that, besides a role
      associated with DNA repair, some proteins of these pathways may also be involved
      in signalling oxidative damage. Recent data also suggested that an oxidative
      environment might be beneficial for parasite survival within the host cell as it
      contributes to iron mobilization from the host's intracellular storages. Besides
      contributing to the understanding of basic aspects of T. cruzi biology, these
      studies are highly relevant since oxidative stress pathways are part of the
      poorly understood mechanisms behind the mode of action of drugs currently used
      against this parasite. By unveiling new peculiar aspects of T. cruzi biology,
      emerging data on DNA repair pathways and other antioxidant defences from this
      parasite have revealed potential new targets for a much needed boost in drug
      development efforts towards a better treatment for Chagas disease. 

PMID- 27036063
TI  - The comet assay: Reflections on its development, evolution and applications.
AB  - The study of DNA damage and its repair is critical to our understanding of human
      aging and cancer. This review reflects on the development of a simple technique,
      now known as the comet assay, to study the accumulation of DNA damage and its
      repair. It describes my journey into aging research and the need for a method
      that sensitively quantifies DNA damage on a cell-by-cell basis and on a day-by
      day basis. My inspirations, obstacles and successes on the path to developing
      this assay and improving its reliability and sensitivity are discussed. Recent
      modifications, applications, and the process of standardizing the technique are
      also described. What was once untried and unknown has become a technique used
      around the world for understanding and monitoring DNA damage. The comet assay's
      use has grown exponentially in the new millennium, as emphasis on studying
      biological phenomena at the single-cell level has increased. I and others have
      applied the technique across cell types (including germ cells) and species
      (including bacteria). As it enters new realms and gains clinical relevance, the
      comet assay may very well illuminate human aging and its prevention. 

PMID- 27036064
TI  - Genome defense against exogenous nucleic acids in eukaryotes by non-coding DNA
      occurs through CRISPR-like mechanisms in the cytosol and the bodyguard protection
      in the nucleus.
AB  - In this review, the protective function of the abundant non-coding DNA in the
      eukaryotic genome is discussed from the perspective of genome defense against
      exogenous nucleic acids. Peripheral non-coding DNA has been proposed to act as a
      bodyguard that protects the genome and the central protein-coding sequences from
      ionizing radiation-induced DNA damage. In the proposed mechanism of protection,
      the radicals generated by water radiolysis in the cytosol and IR energy are
      absorbed, blocked and/or reduced by peripheral heterochromatin; then, the DNA
      damage sites in the heterochromatin are removed and expelled from the nucleus to
      the cytoplasm through nuclear pore complexes, most likely through the formation
      of extrachromosomal circular DNA. To strengthen this hypothesis, this review
      summarizes the experimental evidence supporting the protective function of non
      coding DNA against exogenous nucleic acids. Based on these data, I hypothesize
      herein about the presence of an additional line of defense formed by small RNAs
      in the cytosol in addition to their bodyguard protection mechanism in the
      nucleus. Therefore, exogenous nucleic acids may be initially inactivated in the
      cytosol by small RNAs generated from non-coding DNA via mechanisms similar to the
      prokaryotic CRISPR-Cas system. Exogenous nucleic acids may enter the nucleus,
      where some are absorbed and/or blocked by heterochromatin and others integrate
      into chromosomes. The integrated fragments and the sites of DNA damage are
      removed by repetitive non-coding DNA elements in the heterochromatin and excluded
      from the nucleus. Therefore, the normal eukaryotic genome and the central protein
      coding sequences are triply protected by non-coding DNA against invasion by
      exogenous nucleic acids. This review provides evidence supporting the protective
      role of non-coding DNA in genome defense. 

PMID- 27036065
TI  - The importance of de novo mutations for pediatric neurological disease--It is not
      all in utero or birth trauma.
AB  - The advent of next generation sequencing (NGS, which consists of massively
      parallel sequencing to perform TGS (total genome sequencing) or WES (whole exome
      sequencing)) has abundantly discovered many causative mutations in patients with
      pediatric neurological disease. A surprisingly high number of these are de novo
      mutations which have not been inherited from either parent. For epilepsy, autism
      spectrum disorders, and neuromotor disorders, including cerebral palsy, initial
      estimates put the frequency of causative de novo mutations at about 15% and about
      10% of these are somatic. There are some shared mutated genes between these three
      classes of disease. Studies of copy number variation by comparative genomic
      hybridization (CGH) proceded the NGS approaches but they also detect de novo
      variation which is especially important for ASDs. There are interesting
      differences between the mutated genes detected by CGS and NGS. In summary, de
      novo mutations cause a very significant proportion of pediatric neurological
      disease. 

PMID- 27036066
TI  - Enigmatic 5-hydroxymethyluracil: Oxidatively modified base, epigenetic mark or
      both?
AB  - The aim of this review is to describe the reactions which lead to generation of 5
      hydroxymethyluracil, as well as the repair processes involved in its removal from
      DNA, and its level in various cells and urine. 5-hydroxymethyluracil may be
      formed during the course of the two processes: oxidation/hydroxylation of thymine
      with resultant formation of 5-hydroxymethyluracil paired with adenine (produced
      by reactive oxygen species), and reacting of reactive oxygen species with 5
      methylcytosine forming 5-hydroxymethylcytosine, followed by its deamination to 5
      hydroxymethyluracil mispaired with guanine. However, other, perhaps enzymatic,
      mechanism(s) may be involved in formation of 5-hydroxymethyluracil mispaired with
      guanine. Indeed, this mispair may be also formed as a result of deamination of 5
      hydroxymethylcytosine, recently described "sixth" DNA base. It was demonstrated
      that 5-hydroxymethyluracil paired with adenine can be also generated by TET
      enzymes from thymine during mouse embryonic cell differentiation. Therefore, it
      is possible that 5-hydroxymethyluracil is epigenetic mark. The level of 5
      hydroxymethyluracil in various somatic tissues is relatively stable and resembles
      that observed in lymphocytes, about 0.5/10(6) dN in human colon, colorectal
      cancer as well as various rat and porcine tissues. Experimental evidence suggests
      that SMUG1 and TDG are main enzymes involved in removal of 5-hydroxymethyluracil
      from DNA. 5-hydroxymethyluracil, in form of 5-hydroxymethyluridine, was also
      detected in rRNA, and together with SMUG1 may play a role in rRNA quality
      control. To summarize, 5-hydroxymethyluracil is with no doubt a product of both
      enzymatic and reactive oxygen species-induced reaction. This modification may
      probably serve as an epigenetic mark, providing additional layer of information
      encoded within the genome. However, the pool of 5-hydroxymethyluracil generated
      as a result of oxidative stress is also likely to disturb physiological
      epigenetic processes, and as such may be defined as a lesion. Altogether this
      suggests that 5-hydroxymethyluracil may be either a regulatory or erroneous
      compound. 

PMID- 27036067
TI  - The Comet assay in insects--Status, prospects and benefits for science.
AB  - The Comet assay has been recently adapted to investigate DNA damage in insects.
      The first reports of its use in Drosophila melanogaster appeared in 2002. Since
      then, the interest in the application of the Comet assay to studies of insects
      has been rapidly increasing. Many authors see substantial potential in the use of
      the Comet assay in D. melanogaster for medical toxicology studies. This
      application could allow the testing of drugs and result in an understanding of
      the mechanisms of action of toxins, which could significantly influence the
      limited research that has been performed on vertebrates. The possible
      perspectives and benefits for science are considered in this review. In the last
      decade, the use of the Comet assay has been described in insects other than D.
      melanogaster. Specifically, methods to prepare a cell suspension from insect
      tissues, which is a difficult task, were analyzed and compared in detail.
      Furthermore, attention was paid to any differences and modifications in the
      research protocols, such as the buffer composition and electrophoresis
      conditions. Various scientific fields in addition to toxicological and
      ecotoxicological research were considered. We expect the Comet assay to be used
      in environmental risk assessments and to improve our understanding of many
      important phenomena of insect life, such as metamorphosis, molting, diapause and
      quiescence. The use of this method to study species that are of key importance to
      humans, such as pests and beneficial insects, appears to be highly probable and
      very promising. The use of the Comet assay for DNA stability testing in insects
      will most likely rapidly increase in the future. 

PMID- 27036068
TI  - Contributions of DNA repair and damage response pathways to the non-linear
      genotoxic responses of alkylating agents.
AB  - From a risk assessment perspective, DNA-reactive agents are conventionally
      assumed to have genotoxic risks at all exposure levels, thus applying a linear
      extrapolation for low-dose responses. New approaches discussed here, including
      more diverse and sensitive methods for assessing DNA damage and DNA repair,
      strongly support the existence of measurable regions where genotoxic responses
      with increasing doses are insignificant relative to control. Model monofunctional
      alkylating agents have in vitro and in vivo datasets amenable to determination of
      points of departure (PoDs) for genotoxic effects. A session at the 2013 Society
      of Toxicology meeting provided an opportunity to survey the progress in
      understanding the biological basis of empirically-observed PoDs for DNA
      alkylating agents. Together with the literature published since, this review
      discusses cellular pathways activated by endogenous and exogenous alkylation DNA
      damage. Cells have evolved conserved processes that monitor and counteract a
      spontaneous steady-state level of DNA damage. The ubiquitous network of DNA
      repair pathways serves as the first line of defense for clearing of the DNA
      damage and preventing mutation. Other biological pathways discussed here that are
      activated by genotoxic stress include post-translational activation of cell cycle
      networks and transcriptional networks for apoptosis/cell death. The interactions
      of various DNA repair and DNA damage response pathways provide biological bases
      for the observed PoD behaviors seen with genotoxic compounds. Thus, after
      formation of DNA adducts, the activation of cellular pathways can lead to the
      avoidance of a mutagenic outcome. The understanding of the cellular mechanisms
      acting within the low-dose region will serve to better characterize risks from
      exposures to DNA-reactive agents at environmentally-relevant concentrations. 

PMID- 27036069
TI  - Unraveling the mechanisms of extreme radioresistance in prokaryotes: Lessons from
      nature.
AB  - The last 50 years, a variety of archaea and bacteria able to withstand extremely
      high doses of ionizing radiation, have been discovered. Several lines of evidence
      suggest a variety of mechanisms explaining the extreme radioresistance of
      microorganisms found usually in isolated environments on Earth. These findings
      are discussed thoroughly in this study. Although none of the strategies discussed
      here, appear to be universal against ionizing radiation, a general trend was
      found. There are two cellular mechanisms by which radioresistance is achieved:
      (a) protection of the proteome and DNA from damage induced by ionizing radiation
      and (b) recruitment of advanced and highly sophisticated DNA repair mechanisms,
      in order to reconstruct a fully functional genome. In this review, we critically
      discuss various protecting (antioxidant enzymes, presence or absence of certain
      elements, high metal ion or salt concentration etc.) and repair (Homologous
      Recombination, Single-Strand Annealing, Extended Synthesis-Dependent Strand
      Annealing) mechanisms that have been proposed to account for the extraordinary
      abilities of radioresistant organisms and the homologous radioresistance
      signature genes in these organisms. In addition, and based on structural
      comparative analysis of major radioresistant organisms, we suggest future
      directions and how humans could innately improve their resistance to radiation
      induced toxicity, based on this knowledge. 

PMID- 27036070
TI  - Pediatric acute scrotal pain: A guide to patient assessment and triage.

PMID- 27036071
TI  - Effects of the fibers distribution in the human eardrum: A biomechanical study.
AB  - The eardrum separates the external ear from the middle ear and it is responsible
      to convert the acoustical energy into mechanical energy. It is divided by pars
      tensa and pars flaccida. The aim of this work is to analyze the susceptibility of
      the four quadrants of the pars tensa under negative pressure, to different lamina
      propria fibers distribution. The development of associated ear pathology, in
      particular the formation of retraction pockets, is also evaluated. To analyze
      these effects, a computational biomechanical model of the tympano-ossicular chain
      was constructed using computerized tomography images and based on the finite
      element method. Three fibers distributions in the eardrum middle layer were
      compared: case 1 (eardrum with a circular band of fibers surrounding all
      quadrants equally), case 2 (eardrum with a circular band of fibers that decreases
      in thickness in posterior quadrants), case 3 (eardrum without circular fibers in
      the posterior/superior quadrant). A static analysis was performed by applying
      approximately 3000Pa in the eardrum. The pars tensa of the eardrum was divided in
      four quadrants and the displacement of a central point of each quadrant analyzed.
      The largest displacements of the eardrum were obtained for the eardrum without
      circular fibers in the posterior/superior quadrant.

PMID- 27036072
TI  - Ring apophysis fractures induced by low-load low-angle repetitive flexion in an
      ex-vivo cervine model.
AB  - Ring apophysis fractures of the spine occur in physically-active adolescents
      causing low back pain and the potential for chronic pain. Many of these fractures
      occur without memorable trauma, suggesting that the fractures occur during
      everyday movements and activities. The benign nature of this poorly understood
      potential mechanism of injury hampers appropriate diagnosis and early treatment.
      The purpose of this study was to establish an ex-vivo model of ring apophysis
      fracture and demonstrate that these fractures can be initiated by repetitive non
      traumatic loading. Six 5-vertebra cervine lumbar (L1-L5) motion segments were
      cyclically loaded in low-angle low-load flexion (to 15 degrees  flexion, with
      peak load of 230+/-50N), a representative movement component of daily activities
      for both human and deer lumbar spines. Pinned end conditions replicated
      physiologically realistic loading. Ring apophysis fractures were created under
      low-load low-angle conditions in healthy vertebrae of similar bone mineral
      density and a similar degree of skeletal maturity to adolescent humans. All
      specimens developed ring apophysis fractures, some as early as 1400 cycles. The
      load-displacement data, and hysteresis loops during the cyclic loading, suggest
      that the fractures occurred gradually, i.e., without trauma. The ease at which
      these fractures were created suggests that ring apophysis fractures may be more
      prevalent than current diagnosis rates. Therefore, clinically, healthcare
      providers should include the potential for ring apophysis fracture in the
      differential diagnosis of all physically-active adolescents who present with back
      pain.

PMID- 27036073
TI  - The antibacterial activity of levofloxacin eye drops against staphylococci using
      an in vitro pharmacokinetic model in the bulbar conjunctiva.
AB  - The incidence of fluoroquinolone-resistant staphylococcal isolates from the
      conjunctival sac is increasing. We compared pharmacological effects of
      levofloxacin (LVFX) against Staphylococcus epidermidis using an in vitro
      pharmacokinetic (PK) model simulating the concentration in the bulbar conjunctiva
      after applying eye drops of 0.5% and 1.5% LVFX. We used S. epidermidis
      conjunctival sac isolates [minimum inhibitory concentrations (MICs) of LVFX,
      0.125 MUg/mL]. LVFX-resistant strains were obtained from parental strains after
      culture with LVFX. The in vitro PK model simulated the concentration in the
      bulbar conjunctiva following three topical applications of 0.5% or 1.5% LVFX
      ophthalmic solution (0, 4, and 8 h) to rabbit eyes. Parental and LVFX-resistant
      strains were exposed to LVFX in the in vitro PK model, and changes in viable
      bacterial counts were evaluated for 12 h. The MICs of LVFX for the resistant
      isolates were 2-32 times higher than the parental strain, and those with MICs >=2
      ug/mL had mutations in the quinolone resistance-determining region. The PK model
      simulation predicts that 1.5% LVFX exerts bactericidal and bacteriostatic effects
      against strains with MICs of 0.125-2 and 4 MUg/mL, respectively, whereas 0.5%
      LVFX would only be effective against strains with MICs of 0.125-1 MUg/mL. The PK
      model predicts that the 1.5% LVFX ophthalmic solution exhibits a stronger
      bactericidal effect against resistant staphylococci in the bulbar conjunctiva
      than the 0.5% LVFX ophthalmic solution. 

PMID- 27036074
TI  - Thiol Adsorption on and Reduction of Copper Oxide Particles and Surfaces.
AB  - The adsorption of 1-dodecanethiol at room temperature and at 75  degrees C on
      submicron cuprous and cupric oxide particles suspended in ethanol has been
      investigated by X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and
      transmission electron microscopy. Thiol adsorption occurs in all cases via Cu-S
      bond formation, with partial dissolution of CuO at 75  degrees C and formation of
      a copper-thiolate complex replacement layer. Regardless of temperature, the
      surface of the CuO particles is essentially completely reduced to either Cu2O or
      metallic copper, as evidenced by loss of the characteristic Cu(2+) XPS features
      of dried powder samples. Companion ultrahigh-vacuum studies have been performed
      by dosing clean, oxygen-dosed, and ozone-treated single crystal Cu(111) with
      methanethiol (MT) gas at room temperature. In the latter case, the surface
      corresponds to CuO/Cu(111). XPS confirms MT adsorption in all cases, with an S 2p
      peak binding energy of 162.9 +/- 0.1 eV, consistent with methanethiolate
      adsorption. Heating of MT-covered Cu(111) and oxygen-dosed Cu(111) leads to
      decomposition/desorption of the MT by 100  degrees C and formation of copper
      sulfide with an S 2p binding energy of 161.8 eV. Dosing CuO/Cu(111) with 50-200 L
      of MT leads to only partial reduction/removal of the CuO surface layers prior to
      methanethiolate adsorption. This is confirmed by ultraviolet photoelectron
      spectroscopy (UPS), which measures the occupied states near the Fermi level. For
      both the colloidal CuO and single crystal CuO/Cu(111) studies, the reduction of
      the Cu(2+) surface is believed to occur by formation and desorption of the
      corresponding dithiol prior to thiolate adsorption.

PMID- 27036075
TI  - Prior to Jettisoning the Radiology "Clinical Year," the Medical School Fourth
      Year Warrants Understanding.

PMID- 27036076
TI  - Yield of Preoperative Whole-body CT in Patients Presenting with Single Brain
      Malignancy:: Experience at a Tertiary-care Center.
AB  - RATIONALE AND OBJECTIVES: Single brain malignancy (SBM) often poses a diagnostic
      dilemma, with differential diagnosis of primary brain malignancy (PBM) versus
      metastasis commonly rendered. This study assesses the yield of preoperative
      computed tomography (CT) of the chest, abdomen, and pelvis (CTCAP) in patients
      with SBM. MATERIALS AND METHODS: Institutional review board (IRB)-approved
      retrospective review of the imaging database at a tertiary-care center was
      performed for patients with magnetic resonance findings compatible with a
      diagnosis of SBM. Demographic information, lesion characteristics (location and
      size), and pathology were recorded. Findings of CTCAP for metastatic workup prior
      to SBM excisional biopsy were also documented, if performed. RESULTS: Eighty-six
      of 92 patients with new diagnosis of SBM on MR imaging had subsequent lesion
      resection and pathology consistent with malignancy. PBM accounted for 51 cases
      (59%) and metastasis accounted for 35 cases (41%). When stratified by age group,
      PBM was more common in patients <50 years old (15 of 18 (83%)), whereas similar
      rates of PBM and metastatic disease were identified in older patients. When
      stratified by lesion size, PBM was more common in tumors >=40 mm (25 of 31
      (81%)), whereas similar rates of PBM and metastatic disease were identified in
      smaller lesions. Lung cancer was the most common CTCAP and pathology-confirmed
      source of metastatic SBM (68% and 66%, respectively). CONCLUSIONS: The yield of
      preoperative CTCAP can be increased by targeting patients older than 50 years of
      age with SBMs smaller than 40 mm in size.

PMID- 27036077
TI  - Surgical Versus Percutaneous Femoral Access for Delivery of Large-Bore
      Cardiovascular Devices (from the PARTNER Trial).
AB  - It is unclear if surgical exposure confers a risk advantage compared with a
      percutaneous approach for patients undergoing endovascular procedures requiring
      large-bore femoral artery access. From the randomized controlled Placement of
      Aortic Transcatheter Valve trials A and B and the continued access registries, a
      total of 1,416 patients received transfemoral transcatheter aortic valve
      replacement, of which 857 underwent surgical, and 559 underwent percutaneous
      access. Thirty-day rates of major vascular complications and quality of life
      scores were assessed. Propensity matching was used to adjust for unmeasured
      confounders. Overall, there were 116 major vascular complications (8.2%).
      Complication rates decreased dramatically during the study period. In unadjusted
      analysis, major vascular complications were significantly less common in the
      percutaneous access group (35 [6.3%] vs 81 [9.5%] p = 0.032). However, among 292
      propensity-matched pairs, there was no difference in major vascular complications
      (22 [7.5%] vs 28 [9.6%], p = 0.37). Percutaneous access was associated with fewer
      total in-hospital vascular complications (46 [16%] vs 66 [23%], p = 0.036),
      shorter median procedural duration (97 interquartile range [IQR 68 to 166] vs 121
      [IQR 78 to 194] minutes, p <0.0001), and median length of stay (4 [IQR 2 to 8] vs
      6 [IQR 3 to 10] days, p <0.0001). There were no significant differences in
      quality of life scores at 30 days. Surgical access for large-bore femoral access
      does not appear to confer any advantages over percutaneous access and may be
      associated with more minor vascular complications. 

PMID- 27036078
TI  - A streamlined tethered chromosome conformation capture protocol.
AB  - BACKGROUND: Identification of locus-locus contacts at the chromatin level
      provides a valuable foundation for understanding of nuclear architecture and
      function and a valuable tool for inferring long-range linkage relationships. As
      one approach to this, chromatin conformation capture-based techniques allow
      creation of genome spatial organization maps. While such approaches have been
      available for some time, methodological advances will be of considerable use in
      minimizing both time and input material required for successful application.
      RESULTS: Here we report a modified tethered conformation capture protocol that
      utilizes a series of rapid and efficient molecular manipulations. We applied the
      method to Caenorhabditis elegans, obtaining chromatin interaction maps that
      provide a sequence-anchored delineation of salient aspects of Caenorhabditis
      elegans chromosome structure, demonstrating a high level of consistency in
      overall chromosome organization between biological samples collected under
      different conditions. In addition to the application of the method to defining
      nuclear architecture, we found the resulting chromatin interaction maps to be of
      sufficient resolution and sensitivity to enable detection of large-scale
      structural variants such as inversions or translocations. CONCLUSION: Our
      streamlined protocol provides an accelerated, robust, and broadly applicable
      means of generating chromatin spatial organization maps and detecting genome
      rearrangements without a need for cellular or chromatin fractionation.

PMID- 27036080
TI  - Central role of betaine-homocysteine S-methyltransferase 3 in chondral
      ossification and evidence for sub-functionalization in neoteleost fish.
AB  - BACKGROUND: To better understand the complex mechanisms of bone formation it is
      fundamental that genes central to signaling/regulatory pathways and matrix
      formation are identified. Cell systems were used to analyze genes differentially
      expressed during extracellular matrix mineralization and bhmt3, coding for a
      betaine-homocysteine S-methyltransferase, was shown to be down-regulated in
      mineralizing gilthead seabream cells. METHODS: Levels and sites of bhmt3
      expression were determined by qPCR and in situ hybridization throughout seabream
      development and in adult tissues. Transcriptional regulation of bhmt3 was
      assessed from the activity of promoter constructs controlling luciferase gene
      expression. Molecular phylogeny of vertebrate BHMT was determined from maximum
      likelihood analysis of available sequences. RESULTS: bhmt3 transcript is abundant
      in calcified tissues and localized in cartilaginous structures undergoing
      endo/perichondral ossification. Promoter activity is regulated by transcription
      factors involved in bone and cartilage development, further demonstrating the
      central role of Bhmt3 in chondrogenesis and/or osteogenesis. Molecular phylogeny
      revealed the explosive diversity of bhmt genes in neoteleost fish, while tissue
      distribution of bhmt genes in seabream suggested that neoteleostean Bhmt may have
      undergone several steps of sub-functionalization. CONCLUSIONS: Data on bhmt3 gene
      expression and promoter activity evidences a novel function for betaine
      homocysteine S-methyltransferase in bone and cartilage development, while
      phylogenetic analysis provides new insights into the evolution of vertebrate
      BHMTs and suggests that multiple gene duplication events occurred in neoteleost
      fish lineage. GENERAL SIGNIFICANCE: High and specific expression of Bhmt3 in
      gilthead seabream calcified tissues suggests that bone-specific betaine
      homocysteine S-methyltransferases could represent a suitable marker of chondral
      ossification.

PMID- 27036081
TI  - Expression and purification of human MHC class I-related chain molecule B-alpha1
      domain.
AB  - Major histocompatibility complex (MHC) class I-related chain A/B (MICA/B) is a
      type of stress-induced molecule that plays an important role in tumor
      surveillance. MICA/B shares a similar structure with MHC class I molecules, but
      MICA/B contains a closed cleft, not an open one, in its N-terminal alpha1 domain.
      The alpha 1 domain was believed to have no roles in antigen presentation, because
      the closed cleft provides limited space for binding with known molecules, and the
      cleft of MICA/B have been reported no known functions. To study the possible
      function of the cleft located in human MICA/B's alpha 1 domain, we attempted to
      express the human MICB-alpha1 (hMICB-alpha1) domain allele protein, which is
      approximately 20.5 kDa, by utilizing an Escherichia coli (E. coli) secretory
      pathway. Protein expression was accomplished through the phosphate-limited
      inducible promoter. After purification using ammonium sulfate precipitation,
      phenyl hydrophobic Sepharose, SP Sepharose and HisTrap affinity Sepharose,
      recombinant human MICB-alpha1 (rhMICB-alpha1) was obtained with 94.3% purity. The
      binding capacity of rhMICB-alpha1 with natural killer group 2, member D (NKG2D)
      was evaluated in vitro. The results demonstrated that rhMICB-alpha1 can be
      prepared through the E. coli secretory pathway. Purified rhMICB-alpha1 protein
      was able to functionally bind with NKG2D. This method can be further used to
      obtain functionally active rhMICB-alpha1 protein, which can served as the basis
      for further studies of the possible function of the MICB cleft.

PMID- 27036082
TI  - Lost in translation? How adults living with Cystic Fibrosis understand treatment
      recommendations from their healthcare providers, and the impact on adherence to
      therapy.
AB  - OBJECTIVE: This study builds on the limited research documenting Cystic Fibrosis
      (CF) patients' understanding of treatment recommendations and how this may impact
      adherence to therapy. METHODS: We surveyed adults with CF and their healthcare
      professional (HCP) to capture treatment recommendations provided by the HCP, and
      patients' knowledge, and frequency of performance, of these recommendations. We
      classified CF participants' understanding of treatment recommendations
      (correct/incorrect) as compared to the actual recommendations made by the HCP. We
      computed CF participants' adherence in relation to HCP treatment recommendations
      and to their own understanding of treatment recommendations (adherent/non
      adherent). RESULTS: Complete HCP and patient data were available for 42
      participants. The recommended treatment frequency was correctly understood by 0%
      87.8% of CF participants. Adherence to HCP treatment recommendations ranged from
      0 to 68.3% (mean 45.4%+/-21.5), and rates were low (<33%) for acapella,
      percussion/postural drainage, tobramycin nebulization and insulin. Participants'
      adherence was greater when calculated in relation to participants' understanding
      of treatment recommendations (62.4%+/-25.1) than when calculated in relation to
      actual HCP treatment recommendations (45.4%+/-21.5%) (p=0.009). CONCLUSION AND
      PRACTICE IMPLICATIONS: Adults with CF misunderstand treatment recommendations;
      this likely affects treatment adherence. Interventions to ensure HCPs use
      effective communication strategies are needed.

PMID- 27036079
TI  - Assessment of the genetic variance of late-onset Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex genetic disorder with no effective
      treatments. More than 20 common markers have been identified, which are
      associated with AD. Recently, several rare variants have been identified in
      Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2
      (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the
      many successes, the genetic architecture of AD remains unsolved. We used Genome
      wide Complex Trait Analysis to (1) estimate phenotypic variance explained by
      genetics; (2) calculate genetic variance explained by known AD single nucleotide
      polymorphisms (SNPs); and (3) identify the genomic locations of variation that
      explain the remaining unexplained genetic variance. In total, 53.24% of
      phenotypic variance is explained by genetics, but known AD SNPs only explain
      30.62% of the genetic variance. Of the unexplained genetic variance,
      approximately 41% is explained by unknown SNPs in regions adjacent to known AD
      SNPs, and the remaining unexplained genetic variance outside these regions. 

PMID- 27036083
TI  - Biobehavioral determinants of glycemic control in type 2 diabetes: A systematic
      review and meta-analysis.
AB  - OBJECTIVES: To conduct a model-driven meta-analysis of correlational research on
      psychological and motivational predictors of diabetes outcomes, with adherence
      factors as mediators. METHODS: A comprehensive literature search of published and
      unpublished studies located a sample of 775 individual correlational or
      predictive studies reported across 739 research reports. RESULTS: Results varied
      according to the outcome variable included in the regression models. Depression
      had a larger negative effect on adherence to physical activity than on dietary
      adherence. Coping and self-efficacy were strongly related to dietary adherence,
      which was strongly related to improved glycemic control. Medication adherence was
      related to glycosylated hemoglobin, whereas medications and self-monitoring were
      related to fasting blood glucose. Adding appointment keeping to the models did
      not significantly alter the results. CONCLUSION: Self-efficacy was the most
      consistent predictor of all adherence behaviors and dietary adherence was the
      most significant predictor of HbA1c. Physical activity was the most predictive
      factor of BMI and glucose self-monitoring the most predictive of FBG. PRACTICE
      IMPLICATIONS: Metabolic control is a primary goal in T2DM, so the best pathway to
      attaining that goal appears to be an emphasis on self-efficacy and dietary
      adherence.

PMID- 27036084
TI  - Comparison of partial extraction reagents for assessing potential bioavailability
      of heavy metals in sediments.
AB  - Assessment of heavy metal bioavailability in sediments is complex because of the
      number of partial extraction methods available for the assessment and the general
      lack of certified reference materials. This study evaluates five different
      extraction methodologies to ascertain the relative strengths and weaknesses of
      each method. The results are then compared to previously published work to
      ascertain the most effective partial extraction technique, which was established
      to dilute (0.75-1M) nitric acid solutions. These results imply that single
      reagent; weak acid extractions provide a better assessment of potentially
      bioavailable metals than the chelating agents used in sequential extraction
      methods. 

PMID- 27036085
TI  - Ecotoxicological potential of non-steroidal anti-inflammatory drugs (NSAIDs) in
      marine organisms: Bioavailability, biomarkers and natural occurrence in Mytilus
      galloprovincialis.
AB  - Pharmaceuticals represent a major environmental concern since the knowledge on
      their occurrence, distribution and ecotoxicological potential is still limited
      particularly in coastal areas. In this study, bioaccumulation and cellular
      effects of various non steroidal anti-inflammatory drugs (NSAIDs) were
      investigated in mussels Mytilus galloprovincialis to reveal whether common
      molecules belonging to the same therapeutic class might cause different effects
      on non target organisms. Organisms exposed to environmental concentrations of
      acetaminophen (AMP), diclofenac (DIC), ibuprofen (IBU), ketoprofen (KET) and
      nimesulide (NIM) revealed a significant accumulation of DIC, IBU and NIM, while
      AMP and KET were always below detection limit. Nonetheless, for all tested
      NSAIDs, measurement of a large panel of ecotoxicological biomarkers highlighted
      impairment of immunological parameters, onset of genotoxicity and modulation of
      lipid metabolism, oxidative and neurotoxic effects. Laboratory results were
      integrated with a field study which provided the first evidence on the occurrence
      of DIC, IBU and NIM in tissues of wild mussels sampled during summer months from
      an unpolluted, touristic area of Central Adriatic Sea. Overall results
      demonstrated M. galloprovincialis as a good sentinel species for monitoring
      presence and ecotoxicological hazard of pharmaceuticals in the Mediterranean. 

PMID- 27036086
TI  - Associations among chronic kidney disease, high total p-cresylsulfate and left
      ventricular systolic dysfunction.
AB  - BACKGROUND: A significant number of patients with chronic kidney disease (CKD)
      have cardiac abnormalities, and left ventricular systolic dysfunction (LVSD) is a
      common manifestation. p-Cresylsulfate (PCS), a protein-bound uraemic retention
      solute, is known to cause endothelial dysfunction and possibly plays a role in
      coronary atherosclerosis. Furthermore, the associations among serum total PCS,
      major adverse cardiovascular events, all-cause mortality, and QTc prolongation
      have also been found in previous studies. We thus investigated the association of
      total PCS and CKD with LVSD in the clinical setting. METHODS: We included 403
      consecutive patients with stable angina. To evaluate LV function, all patients
      underwent echocardiography. To measure the serum total PCS concentrations and
      estimated glomerular filtration rate (eGFR), blood samples were obtained.
      RESULTS: Multiple regression analysis showed that left atrium diameter, left
      ventricular mass index, end diastolic interventricular septal thickness, left
      ventricular end-systolic diameter, left ventricular end-systolic volume, stroke
      volume, left ventricular end-systolic volume index, left ventricular ejection
      fraction (LVEF), and the interventricular septum/posterior wall of the left
      ventricle were independently associated with total PCS (all p<0.05). In addition,
      a significantly decreased LVEF was present in patients with lower and higher
      serum total PCS and with CKD, and with higher serum total PCS and without CKD
      than from those with lower serum total PCS concentrations and without CKD
      (p=0.004). In the multivariate logistic regression analysis, when patients
      without CKD and lower PCS were used as reference group, patients with the higher
      total PCS concentration and without CKD had an odds ratio of 3.59 for the risk of
      LVSD, the lower total PCS concentration and with CKD had an odds ratio of 3.89
      for the risk of LVSD, and the higher total PCS concentration and with CKD had an
      odds ratio of 4.04 for the risk of LVSD (p=0.039, p=0.038, and p=0.020,
      respectively). CONCLUSIONS: High serum concentrations of total PCS or CKD, or
      both, represent an increased risk of impaired LV systolic function in stable
      angina patients.

PMID- 27036087
TI  - Testicular infection in brucellosis: Report of 34 cases.
AB  - BACKGROUND/PURPOSE: To present clinical and laboratory features, treatment
      options, and outcome in patients with brucellar testicular infection and to
      compare them with analogous in brucellar patients without testicular involvement.
      METHODS: Thirty four brucellar patients with testicular infection treated in two
      general hospitals in the Republic of Macedonia, during the period 1998-2009, were
      retrospectively analyzed. Their clinical and laboratory characteristics were
      compared with analogous in 364 male brucellar patients without testicular
      infection, who were treated at the same hospitals during the same time period.
      RESULTS: Brucellar testicular infection was evident in 34 (8.5%) out of 398 male
      patients with brucellosis. The median age of the patients was 46.5 years. In all
      patients testicular involvement was presented as an acute form with a median
      duration of 5 days (range, 2-14 days) prior to diagnosis. Twenty-three of the
      patients had at least one other simultaneous focal infection. After starting with
      the treatment testicular infection lasted a median 10 days, range 7-21 days.
      Brucellar patients with testicular infection when compared with other brucellar
      patients more frequently manifested fever (97% vs. 61%), concomitant spondylitis
      (32% vs. 16%), and urinary system involvement (12% vs. 2%). Also, the relapse
      rate in patients with testicular involvement was significantly higher (24% vs.
      9%). CONCLUSION: In endemic regions brucellosis should be taken into
      consideration in any patient with testicular infection. Brucellar testicular
      involvement is usually characterized with a severe acute clinical presentation
      and a high percentage of relapses which entails the need of timely recognition
      and proper treatment duration of at least 60 days.

PMID- 27036088
TI  - The Relationship Between Body Image and Domains of Sexual Functioning Among
      Heterosexual, Emerging Adult Women.
AB  - INTRODUCTION: Research suggests that body image affects sexual functioning, but
      the relationship between specific types of body image (evaluative, affective, and
      behavioral) and domains of sexual functioning (desire, arousal, and orgasm) has
      not been investigated. AIM: To determine whether, and to what degree, body image
      concerns (evaluative, affective, and behavioral) influence aspects of women's
      sexual functioning (desire, arousal, and orgasm). METHODS: Eighty-eight sexually
      active women in heterosexual romantic relationships completed surveys assessing
      evaluative, affective, and behavioral body image and sexual functioning. Body
      composition data also were collected using dual energy x-ray absorptiometry. MAIN
      OUTCOME MEASURES: Sexual functioning was assessed using the desire, arousal, and
      orgasm subscales of the Female Sexual Functioning Index. RESULTS: Hierarchical
      multiple regression analysis indicated that poor evaluative, affective, and
      behavioral body image were detrimental to women's sexual functioning.
      Specifically, dissatisfaction with one's body predicted decrements in desire
      (beta = -0.31, P < .05) and arousal (beta = -0.35, P < .01). Similarly, feeling
      that others evaluate one's body negatively predicted decrements in desire (beta =
      0.22, P < .05) and arousal (beta = 0.35, P < .01). Feeling negatively about one's
      appearance predicted decrements in arousal (beta = 0.26, P < .05). Negative
      thoughts and feelings about one's body during a sexual encounter (body image self
      consciousness) predicted decrements in arousal (beta = -0.37, P < .01) and orgasm
      (beta = -0.25, P < .05). CONCLUSION: Findings from this study suggest important
      linkages between body image and sexual functioning constructs and indicates that
      interventions to improve body image could have concomitant benefits related to
      sexual experience.

PMID- 27036089
TI  - Glucose transporter 5 (GLUT5)-like immunoreactivity is localized in subsets of
      neurons and glia in the rat brain.
AB  - This study aimed at examining the distribution of glucose transporter 5 (GLUT5),
      which preferentially transports fructose, in the rat brain by
      immunohistochemistry and Western blotting. Small immunoreactive puncta (less than
      0.7MUm) were sparsely distributed all over the brain, some of which appeared to
      be associated with microglial processes detected by an anti-ionized calcium
      binding adapter molecule 1 (Iba-1) monoclonal antibody. In addition, some of
      these immunoreactive puncta seemed to be associated with tanycyte processes that
      were labeled with anti-glial fibrillary acidic protein (GFAP) monoclonal
      antibody. Ependymal cells were also found to be immunopositive for GLUT5.
      Furthermore, several noticeable GLUT5 immunoreactive profiles were observed.
      GLUT5 immunoreactive neurons, confirmed by double staining with neuronal nuclei
      (NeuN), were seen in the entopeduncular nucleus and lateral hypothalamus.
      Cerebellar Purkinje cells were immunopositve for GLUT5. Dense accumulation of
      immunoreactive puncta, some of which were neuronal elements (confirmed by
      immunoelectron microscopy), were observed in the optic tract and their terminal
      fields, namely, superior colliculus, pretectum, nucleus of the optic tract, and
      medial terminal nucleus of the optic tract. In addition to the associated areas
      of the visual system, the vestibular and cochlear nuclei also contained dense
      GLUT5 immunoreactive puncta. Western blot analysis of the cerebellum indicated
      that the antibody used recognized the 33.5 and 37.0kDa bands that were also
      contained in jejunum and kidney extracts. Thus, these results suggest that GLUT5
      may transport fructose in subsets of the glia and neurons for an energy source of
      these cells.

PMID- 27036090
TI  - Development and function of tissue resident macrophages in mice.
AB  - Macrophages are important for tissue development, homeostasis as well as immune
      response upon injury or infection. For a long time they were only seen as one
      uniform group of phagocytes with a common origin and similar functions. However,
      this view has been challenged in the last decade and revealed a complex diversity
      of tissue resident macrophages. Here, we want to present the current view on
      macrophage development and tissue specification and we will discuss differences
      as well as common patterns between heterogeneous macrophage subpopulations.

PMID- 27036091
TI  - Human neutrophils in auto-immunity.
AB  - Human neutrophils have great capacity to cause tissue damage in inflammatory
      diseases via their inappropriate activation to release reactive oxygen species
      (ROS), proteases and other tissue-damaging molecules. Furthermore, activated
      neutrophils can release a wide variety of cytokines and chemokines that can
      regulate almost every element of the immune system. In addition to these
      important immuno-regulatory processes, activated neutrophils can also release,
      expose or generate neoepitopes that have the potential to break immune tolerance
      and result in the generation of autoantibodies, that characterise a number of
      human auto-immune diseases. For example, in vasculitis, anti-neutrophil
      cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or
      myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are
      the main effector cells of vascular damage. In other auto-immune diseases, these
      neutrophil-derived neoepitopes may arise from a number of processes that include
      release of granule enzymes and ROS, changes in the properties of components of
      their plasma membrane as a result of activation or apoptosis, and via the release
      of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that
      contain chromatin that is decorated with granule enzymes (including citrullinated
      proteins) that can act as neo-epitopes to generate auto-immunity. This review
      therefore describes the processes that can result in neutrophil-mediated auto
      immunity, and the role of neutrophils in the molecular pathologies of auto-immune
      diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE). We discuss the potential role of NETs in these processes and
      some of the debate in the literature regarding the role of this phenomenon in
      microbial killing, cell death and auto-immunity.

PMID- 27036092
TI  - Evidential breath alcohol analysis and the venous blood-to-breath ratio.

PMID- 27036093
TI  - A multi-laboratory evaluation of microelectrode array-based measurements of
      neural network activity for acute neurotoxicity testing.
AB  - There is a need for methods to screen and prioritize chemicals for potential
      hazard, including neurotoxicity. Microelectrode array (MEA) systems enable
      simultaneous extracellular recordings from multiple sites in neural networks in
      real time and thereby provide a robust measure of network activity. In this
      study, spontaneous activity measurements from primary neuronal cultures treated
      with three neurotoxic or three non-neurotoxic compounds was evaluated across four
      different laboratories. All four individual laboratories correctly identifed the
      neurotoxic compounds chlorpyrifos oxon (an organophosphate insecticide),
      deltamethrin (a pyrethroid insecticide) and domoic acid (an excitotoxicant). By
      contrast, the other three compounds (glyphosate, dimethyl phthalate and
      acetaminophen) considered to be non-neurotoxic ("negative controls"), produced
      only sporadic changes of the measured parameters. The results were consistent
      across the different laboratories, as all three neurotoxic compounds caused
      concentration-dependent inhibition of mean firing rate (MFR). Further, MFR
      appeared to be the most sensitive parameter for effects of neurotoxic compounds,
      as changes in electrical activity measured by mean frequency intra burst (MFIB),
      and mean burst duration (MBD) did not result in concentration-response
      relationships for some of the positive compounds, or required higher
      concentrations for an effect to be observed. However, greater numbers of
      compounds need to be tested to confirm this. The results obtained indicate that
      measurement of spontaneous electrical activity using MEAs provides a robust
      assessment of compound effects on neural network function.

PMID- 27036094
TI  - Feasibility of Applied Gaming During Interdisciplinary Rehabilitation for
      Patients With Complex Chronic Pain and Fatigue Complaints: A Mixed-Methods Study.
AB  - BACKGROUND: Applied gaming holds potential as a convenient and engaging means for
      the delivery of behavioral interventions. For developing and evaluating feasible
      computer-based interventions, policy makers and designers rely on limited
      knowledge about what causes variation in usage. OBJECTIVE: In this study, we
      looked closely at why and by whom an applied game (LAKA) is demanded and whether
      it is feasible (with respect to acceptability, demand, practicality,
      implementation, and efficacy) and devised a complementary intervention during an
      interdisciplinary rehabilitation program (IRP) for patients with complex chronic
      pain and fatigue complaints. METHODS: A mixed-methods design was used.
      Quantitative process analyses and assessments of feasibility were carried out
      with patients of a Dutch rehabilitation center who received access to LAKA
      without professional support during a 16-week interdisciplinary outpatient
      program. The quantitative data included records of routinely collected baseline
      variables (t0), additional surveys to measure technology acceptance before (t1)
      and after 8 weeks of access to LAKA (t2), and automatic log files of usage
      behavior (frequency, length, and progress). Subsequently, semistructured
      interviews were held with purposively selected patients. Interview codes
      triangulated and illustrated explanations of usage and supplemented quantitative
      findings on other feasibility domains. RESULTS: Of the 410 eligible patients who
      started an IRP during the study period, 116 patients participated in additional
      data collections (108 with problematic fatigue and 47 with moderate or severe
      pain). Qualitative data verified that hedonic motivation was the most important
      factor for behavioral intentions to use LAKA (P<.001). Moreover, quotes
      illustrated a positive association between usage intentions (t1) and baseline
      level (t0) coping by active engagement (Spearman rho=0.25; P=.008) and why
      patients who often respond by seeking social support were represented in a group
      of 71 patients who accessed the game (P=.034). The median behavioral intention to
      use LAKA was moderately positive and declined over time. Twenty patients played
      the game from start to finish. Behavioral change content was recognized and seen
      as potentially helpful by interview respondents who exposed themselves to the
      content of LAKA. CONCLUSIONS: Variation in the demand for applied gaming is
      generally explained by perceived enjoyment and effort and by individual
      differences in coping resources. An applied game can be offered as a feasible
      complementary intervention for more patients with complex chronic pain or fatigue
      complaints by embedding and delivering in alignment with patient experiences.
      Feasibility, effectiveness, and cost-effectiveness can be evaluated in a full
      scale evaluation. New observations elicit areas of further research on the usage
      of computer-based interventions.

PMID- 27036095
TI  - Chlorination of benzothiazoles and benzotriazoles and transformation products
      identification by LC-HR-MS/MS.
AB  - The fate of four benzotriazoles [1-H-benzotriazole (1-H-BTRi), tolyltriazole
      (TTRi), xylyltriazole (XTRi) and 1-hydroxy-benzotriazole (1-OH-BTRi)] and three
      benzothiazoles [benzothiazole (BTH), 2-hydroxy-benzothiazole (2-OH-BTH) and 2
      amino-benzothiazole (2-amino-BTH)], during chlorination batch experiments was
      investigated. In the first step, their degradation under different experimental
      conditions (applied molar ratio of NaOCl and the target contaminant (m.r.),
      reaction's contact time, pH value of the reaction's solution and the influence of
      total suspended solids (TSS) presence) was investigated and their removal
      kinetics parameters (kobs and t1/2) were determined. In the second step, LC
      QTOFMS/MS was used for the detection and identification of transformation
      products (TPs) formed during chlorination, through the application of suspect and
      non-target screening approaches. Four and five TPs of XTRi and 2-amino-BTH,
      respectively, were detected and tentatively identified, while 1-H-BTRi was proven
      to be formed by the chlorination of 1-OH-BTRi. Moreover, since the identified TPs
      were also detected in spiked wastewater samples, after lab-scale chlorination
      experiments, toxicity assessment was carried out by ECOSAR calculations for the
      environmental relevance of their occurrence. The proposed chlorinated TPs were
      proven to be more toxic than their parent compounds.

PMID- 27036096
TI  - Novel pre-treatments to control bromate formation during ozonation.
AB  - Worldwide water shortage increase and water quality depletion from microbial and
      chemical compounds, pose significant challenges for today's water treatment
      industry. Both the development of new advanced oxidation technologies, but also
      the enhancement of existing conventional technologies is of high interest. This
      study tested improvements to conventional ozonation that reduce the formation of
      the oxidation-by-product bromate, while maintaining the effectiveness for removal
      emerging contaminants (atrazine). MnO4-, ClO2-, ClO2, ClO-, CH3COOO-, HSO5- or
      S2O8-2 with NH4+ were tested as pre-treatments to ozonation of ground water. Each
      oxidant and NH4+ were added in a single stage or separately prior to ozonation.
      To the best of our knowledge, this is the first study that has tested all the
      above-mentioned oxidants for the same water matrix. Based on our results, the
      most promising pre-treatments were MnO4--NH4+, ClO2--NH4+ and ClO2-NH4+. MnO4-
      NH4+ was the only pre-treatment that did not inhibit atrazine removal. When
      compared with the previously proposed Cl2/NH4+ pre-treatment, MnO4-+NH4+ was
      found as effective for preventing BrO3- formation, while atrazine removal was
      higher. In addition, MnO4-+NH4+ can be added in a single stage (compared to the 2
      stage addition of Cl2/NH4+) without causing the formation of potentially harmful
      chlorination-by-products.

PMID- 27036097
TI  - A host stage-structured model of enzootic West Nile virus transmission to explore
      the effect of avian stage-dependent exposure to vectors.
AB  - Though seasonal West Nile virus (WNV) outbreaks have been widely observed to be
      associated with the end of the avian nesting season, specific ecological
      mechanisms accounting for this synchronicity remain poorly understood. In this
      paper we develop and evaluate a novel mathematical model of enzootic WNV
      transmission to gain insight into the mechanisms responsible for structuring WNV
      dynamics. We incorporate avian (host) stage-structure (nestling, fledgling, and
      adult) and within-species heterogeneity in the form of stage-specific mosquito
      (vector) biting rates. We determine the extent to which temporal fluctuations in
      host stage and vector abundance throughout the season, along with the
      differential exposure of these stages to mosquito bites, affect the timing and
      magnitude of WNV outbreaks in the vector population. We find heterogeneity in
      avian stage exposure, particularly an increase in juvenile exposure, to result in
      earlier, more intense transmission. The effects of differential exposure are
      dependent upon vector abundance, both at carrying capacity as well as during
      initial stages of nestling production.

PMID- 27036098
TI  - First- and second-order contrast sensitivity functions reveal disrupted visual
      processing following mild traumatic brain injury.
AB  - Vision is disrupted by traumatic brain injury (TBI), with vision-related
      complaints being amongst the most common in this population. Based on the neural
      responses of early visual cortical areas, injury to the visual cortex would be
      predicted to affect both 1(st) order and 2(nd) order contrast sensitivity
      functions (CSFs)-the height and/or the cut-off of the CSF are expected to be
      affected by TBI. Previous studies have reported disruptions only in 2(nd) order
      contrast sensitivity, but using a narrow range of parameters and divergent
      methodologies-no study has characterized the effect of TBI on the full CSF for
      both 1(st) and 2(nd) order stimuli. Such information is needed to properly
      understand the effect of TBI on contrast perception, which underlies all visual
      processing. Using a unified framework based on the quick contrast sensitivity
      function, we measured full CSFs for static and dynamic 1(st) and 2(nd) order
      stimuli. Our results provide a unique dataset showing alterations in sensitivity
      for both 1(st) and 2(nd) order visual stimuli. In particular, we show that TBI
      patients have increased sensitivity for 1(st) order motion stimuli and decreased
      sensitivity to orientation-defined and contrast-defined 2(nd) order stimuli. In
      addition, our data suggest that TBI patients' sensitivity for both 1(st) order
      stimuli and 2(nd) order contrast-defined stimuli is shifted towards higher
      spatial frequencies.

PMID- 27036099
TI  - Ultrasound of alternating frequencies and variable emotional impact evokes
      depressive syndrome in mice and rats.
AB  - Emotional stress is primarily triggered by the cognitive processing of negative
      input; it is regarded as a serious pathogenetic factor of depression that is
      challenging to model in animals. While available stress paradigms achieve
      considerable face and construct validity in modelling depressive disorders,
      broader use of naturalistic stressors instead of the more prevalent models with
      artificial challenges inducing physical discomfort or pain may substantially
      contribute to the development of novel antidepressants. Here, we investigated
      whether a 3-week exposure of Wistar rats and Balb/c mice to unpredictably
      alternating frequencies of ultrasound between the ranges of 20-25 and 25-45kHz,
      which are known to correspond with an emotionally negative and with a neutral
      emotional state, respectively, for small rodents in nature, can induce
      behavioural and molecular depressive-like changes. Both rats and mice displayed
      decreased sucrose preference, elevated "despair" behaviour in a swim test,
      reduced locomotion and social exploration. Rats showed an increased expression of
      SERT and 5-HT2A receptor, a decreased expression of 5-HT1A receptor in the
      prefrontal cortex and hippocampus, diminished BDNF on gene and protein levels in
      the hippocampus. Fluoxetine, administered to rats at the dose of 10mg/kg, largely
      precluded behavioural depressive-like changes. Thus, the here applied paradigm of
      emotional stress is generating an experimental depressive state in rodents, which
      is not related to any physical stressors or pain. In essence, this ultrasound
      stress model, besides enhancing animal welfare, is likely to provide improved
      validity in the modelling of clinical depression and may help advance
      translational research and drug discovery for this disorder. 

PMID- 27036100
TI  - Congenital Lung Malformations: Shifting from Open to Thoracoscopic Surgery.
AB  - BACKGROUND: Over the years the need for surgical treatment, timing of
      intervention, and the type of surgical approach have been discussed, but the
      treatment of congenital lung malformations remains controversial. The aim of this
      study was to compare the thoracotomy approach with the thoracoscopic technique by
      evaluating different surgical outcomes (duration of surgery, postoperative
      hospital stay, and complications). METHODS: All patients operated from January
      2011 to March 2015 for suspected congenital cystic lung were included in the
      study. Patients treated for congenital lobar emphysema and tracheobronchial
      neoplasms were excluded from the study. RESULTS: In the analyzed period, 31
      asymptomatic patients were treated: 18 lung resections were performed with
      thoracotomy (Group A) and 13 with the thoracoscopic approach (Group B). No
      significant differences were observed between the age and weight at surgery,
      length of the procedures, complications, and the need for postoperative intensive
      care between the two groups. The postoperative hospital stay in Group A was twice
      that for Group 2 (p = 0.0009). CONCLUSION: Comparing thoracoscopic surgery with
      the traditional open approach, we confirmed the superiority of minimally invasive
      treatment in terms of postoperative hospital stay. Common technical
      recommendations can help pediatric centers to develop the thoracoscopic approach
      for the treatment of congenital pulmonary malformations.

PMID- 27036101
TI  - Effectiveness of Simulation-Based Education on Childhood Fever Management by
      Taiwanese Parents.
AB  - BACKGROUND: Childhood fever is a common symptom managed by parents at home. Most
      parents do not know the definition of fever, its effect, or its management. To
      establish simulation-based education for parents and evaluate its effectiveness
      for fever management at home are essential for nursing care. This study assesses
      the long-term effects of simulation-based education on information, motivation,
      behavioral skills, and behaviors related to parental fever management in Taiwan.
      METHODS: Cluster random sampling was used to recruit parents having children aged
      from 3 months to 5 years who were attending kindergartens in Kaohsiung, Taiwan. A
      total of 160 parents were randomly assigned into experimental (EP) and control
      (CP) groups equally. Parents in the EP group received simulation-based education
      with fever education brochures, while the CP group received only the brochure.
      Data on parental fever information, motivation, behavioral skills, and management
      behaviors were collected before the 1st day, on the 1st day (except management
      behaviors), at the 6-month, and at the 12-month marks post-training with a self
      developed instrument based on the information-motivation-behavioral skills model.
      RESULTS: The results of a generalized estimating equation analysis indicated that
      the information, motivation, behavioral skills, and management behaviors of all
      participants had improved at the post-test assessment, with the EP group showing
      significantly better improvement than the CP group. This study supports that
      simulation-based education effectively enhances fever management of parents for a
      long period of time. CONCLUSION: Simulation-based education, compared to using
      the brochure, was a better strategy for improving parental information,
      motivation, behavioral skills, and behaviors regarding fever management. We
      suggest that providing community-based education on fever with scenario
      simulation is needed to increase parental competence for child care.

PMID- 27036102
TI  - Development of an algorithm to aid triage decisions for intensive care unit
      admission: a clinical vignette and retrospective cohort study.
AB  - BACKGROUND: Intensive care unit (ICU) admission triage is performed routinely and
      is often based solely on clinical judgment, which could mask biases. A
      computerized algorithm to aid ICU triage decisions was developed to classify
      patients into the Society of Critical Care Medicine's prioritization system. In
      this study, we sought to evaluate the reliability and validity of this algorithm.
      METHODS: Nine senior physicians evaluated forty clinical vignettes based on real
      patients. The reference standard was defined as the priorities ascribed by two
      investigators with full access to patients' records. Agreement of algorithm-based
      priorities with the reference standard and with intuitive priorities provided by
      the physicians were evaluated. Correlations between algorithm prioritization and
      physicians' judgment of the appropriateness of ICU admissions in scarcity and
      nonscarcity settings were also evaluated. Validity was further assessed by
      retrospectively applying this algorithm to 603 patients with requests for ICU
      admission for association with clinical outcomes. RESULTS: Agreement between
      algorithm-based priorities and the reference standard was substantial, with a
      median kappa of 0.72 (interquartile range [IQR] 0.52-0.77). Algorithm-based
      priorities demonstrated higher interrater reliability (overall kappa 0.61, 95%
      confidence interval [CI] 0.57-0.65; median percentage agreement 0.64, IQR 0.59
      0.70) than physicians' intuitive prioritization (overall kappa 0.51, 95% CI 0.47
      0.55; median percentage agreement 0.49, IQR 0.44-0.56) (p = 0.001). Algorithm
      based priorities were also associated with physicians' judgment of
      appropriateness of ICU admission (priorities 1, 2, 3, and 4 vignettes would be
      admitted to the last ICU bed in 83.7%, 61.2%, 45.2%, and 16.8% of the scenarios,
      respectively; p < 0.001) and with actual ICU admission, palliative care
      consultation, and hospital mortality in the retrospective cohort. CONCLUSIONS:
      This ICU admission triage algorithm demonstrated good reliability and validity.
      However, more studies are needed to evaluate a difference in benefit of ICU
      admission justifying the admission of one priority stratum over the others.

PMID- 27036103
TI  - The effect of miscellaneous oral dosage forms on the environmental pollution of
      sulfonamides in pig holdings.
AB  - BACKGROUND: Due to antibiotic treatment of humans and animals, the prevalence of
      bacterial resistances increases worldwide. Especially in livestock farming, large
      quantities of faeces contaminated with antibiotics pose a risk of the carryover
      of the active ingredient to the environment. Accordingly, the aim of the present
      study was the evaluation of the benefit of different oral dosage forms (powder,
      pellets, granula) in pigs concerning the environmental pollution of sulfadiazine.
      Two subtherapeutic dosages were evaluated in powder mixtures to gain information
      about their potential to pollute the pig barn. Furthermore, a new group of pigs
      was kept in the stable after powder feeding of another pig group to determine the
      possible absorption of environmentally distributed antibiotics. Pigs were orally
      treated with three dosage forms. Simultaneously, sedimentation and airborne dust
      were collected and plasma and urine levels were determined. RESULTS: All
      formulations result in comparable plasma and urine levels, but massive
      differences in environmental pollution (powder > pellets, granula). Pigs housing
      in a contaminated barn exhibit traces of sulfadiazine in plasma and urine.
      CONCLUSION: Using pharmaceutical formulations like pellets or granula, the
      environmental pollution of sulfonamides can significantly be diminished due to
      massive dust reduction during feeding.

PMID- 27036104
TI  - Goal orientations of health profession students throughout the undergraduate
      program: a multilevel study.
AB  - BACKGROUND: The achievement goal theory defines two major foci of students'
      learning goals (1) primarily interested in truly mastering a task (mastery
      orientation), and (2) striving to show ones competences to others (performance
      orientation). The present study is undertaken to better understand if and how
      health profession students' goal orientations change during the undergraduate
      program and to what degree gender, academic achievement, and self-efficacy are
      associated with mastery and performance orientation between students and within
      students over time. METHOD: By means of an online questionnaire, students of
      medical, pharmaceutical, and veterinary sciences (N = 2402) were asked to rate
      themselves on mastery orientation, performance orientation, and self-efficacy at
      the beginning of five consecutive semesters. Data on grades and gender were drawn
      from university's files. Multilevel analyses were used for data analysis.
      RESULTS: Students' goal orientations showed relative stability over time, but
      substantial fluctuations within individual students were found. These
      fluctuations were associated with fluctuations in self-efficacy. Students'
      gender, high school grades, study grades, and self-efficacy were all associated
      with differences in mastery or performance orientation between students. Self
      efficacy was the strongest predictor for mastery orientation and grades for
      performance orientation. CONCLUSIONS: The relatively strong association between
      the goal orientations and students' self-efficacy found in this study emphasizes
      the potential of enhancing self-efficacy in health profession students. Also, for
      educators and researchers, fluctuations of both goal orientations within
      individual students are important to consider.

PMID- 27036105
TI  - Prevalence and clinical characteristics of metabolically healthy obese
      individuals and other obese/non-obese metabolic phenotypes in a working
      population: results from the Icaria study.
AB  - BACKGROUND: Metabolically healthy obese (MHO) phenotype may present with distinct
      characteristics compared with those with a metabolically unhealthy obese
      phenotype. Epidemiologic data on the distribution of these conditions in the
      working population are lacking. We aimed to evaluate the prevalence and clinical
      characteristics of MHO and other obese/non-obese metabolic phenotypes in a
      working population. METHODS: Cross-sectional analysis of all subjects who had
      undergone a medical examination with Ibermutuamur Prevention Society from May
      2004 to December 2007. Participants were classified into 5 categories according
      to their body mass index (BMI); within each of these categories, participants
      were further classified as metabolically healthy (MH) or metabolically unhealthy
      (MUH) according to the modified NCEP-ATPIII criteria. A logistic regression
      analysis was performed to evaluate some clinically relevant factors associated
      with a MH status. RESULTS: In the overall population, the prevalence of the MHO
      phenotype was 8.6%. The proportions of MH individuals in the overweight and obese
      categories were: 87.1% (overweight) and 55.5% (obese I-III [58.8, 40.0, and 38.7%
      of the obese I, II, and III categories, respectively]). When the overweight and
      obese categories were considered, compared with individuals who were MUH, those
      who were MH tended to be younger and more likely to be female or participate in
      physical exercise; they were also less likely to smoke, or to be a heavy drinker.
      In the underweight and normal weight categories, compared with individuals who
      were MH, those who were MUH were more likely to be older, male, manual (blue
      collar) workers, smokers and heavy drinkers. Among participants in the MUH,
      normal weight group, the proportion of individuals with a sedentary lifestyle was
      higher relative to those in the MH, normal weight group. The factors more
      strongly associated with the MUH phenotype were BMI and age, followed by the
      presence of hypercholesterolemia, male sex, being a smoker, being a heavy
      drinker, and lack of physical exercise. CONCLUSIONS: The prevalence of
      individuals with a MHO phenotype in the working population is high. This
      population may constitute an appropriate target group in whom to implement
      lifestyle modification initiatives to reduce the likelihood of transition to a
      MUH phenotype.

PMID- 27036107
TI  - Syndrome of inappropriate antidiuretic hormone in a patient with leptomeningeal
      carcinomatosis.
AB  - BACKGROUND: Leptomeningeal carcinomatosis is a condition in which metastatic
      cancer cells infiltrate the meninges of the brain and spinal cord, progressing to
      also involve the cerebrospinal fluid. Incidence of leptomeningeal carcinomatosis
      arising from an esophageal cancer is particularly rare. CASE PRESENTATION: Here,
      we present a case report of a 76-year-old Caucasian man with a history of
      esophageal adenocarcinoma status-post chemoradiation followed by resection. He
      was admitted to our unit for intractable headache, nausea without emesis,
      anorexia, weakness, gait instability, delirium, syncope, and near syncope. Our
      diagnostic workup revealed leptomeningeal carcinomatosis and syndrome of
      inappropriate antidiuretic hormone. Our patient was treated with lumbar puncture
      for the headache, methotrexate for the leptomeningeal carcinomatosis, and table
      salt for the syndrome of inappropriate antidiuretic hormone. Despite our best
      efforts, our patient died 6 weeks posttreatment. CONCLUSIONS: Understanding the
      molecular pathogenesis of the development of syndrome of inappropriate
      antidiuretic hormone associated with leptomeningeal carcinomatosis from
      metastatic esophageal adenocarcinoma would help us to identify patients at risk
      and treat them accordingly.

PMID- 27036106
TI  - Using biological networks to integrate, visualize and analyze genomics data.
AB  - Network biology is a rapidly developing area of biomedical research and reflects
      the current view that complex phenotypes, such as disease susceptibility, are not
      the result of single gene mutations that act in isolation but are rather due to
      the perturbation of a gene's network context. Understanding the topology of these
      molecular interaction networks and identifying the molecules that play central
      roles in their structure and regulation is a key to understanding complex
      systems. The falling cost of next-generation sequencing is now enabling
      researchers to routinely catalogue the molecular components of these networks at
      a genome-wide scale and over a large number of different conditions. In this
      review, we describe how to use publicly available bioinformatics tools to
      integrate genome-wide 'omics' data into a network of experimentally-supported
      molecular interactions. In addition, we describe how to visualize and analyze
      these networks to identify topological features of likely functional relevance,
      including network hubs, bottlenecks and modules. We show that network biology
      provides a powerful conceptual approach to integrate and find patterns in genome
      wide genomic data but we also discuss the limitations and caveats of these
      methods, of which researchers adopting these methods must remain aware. 

PMID- 27036108
TI  - Flow cytometric analysis of platelets type 2 diabetes mellitus reveals 'angry'
      platelets.
AB  - BACKGROUND: The function of platelets have extended way beyond the horizon of
      haemostasis and thrombosis, and are recognised as active participants in vascular
      inflammation, as well as in prothrombotic complications of cardiovascular
      diseases. We describe and compare platelet function in type II diabetes (with and
      without cardiovascular manifestation) and healthy individuals using scanning
      electron microscopy and flow cytometry. METHODS: Thirty subjects were recruited
      per group and informed consent was obtained from all participants. Diabetic
      patients were recruited from the diabetic clinic of the Steve Biko Academic
      Hospital (South Africa). Blood samples were drawn from all participants so that
      platelet specific antigens were analyzed in citrated whole blood. The platelet
      parameters used in the study were platelet identifiers (CD41 and CD42) and
      markers of platelet activation (CD62 and CD63). RESULTS: Results show that,
      compared to healthy individuals, both diabetic groups showed a significant
      difference in both platelet identifiers (CD41-PE, CD42b-PE) as well as markers
      indicating platelet activation (CD62P-PE and CD63-PE). INTERPRETATION: The flow
      cytometric data shows that the platelet surface receptors and platelet activation
      are statistically elevated. This is suggestive of enhanced platelet activation
      and it appears as if platelets are displaying 'angry' behaviour. The lysosomal
      granules may play a significant role in diabetes with cardiovascular
      complications. These results were confirmed by ultrastructural analysis.

PMID- 27036109
TI  - Novel personalized pathway-based metabolomics models reveal key metabolic
      pathways for breast cancer diagnosis.
AB  - BACKGROUND: More accurate diagnostic methods are pressingly needed to diagnose
      breast cancer, the most common malignant cancer in women worldwide. Blood-based
      metabolomics is a promising diagnostic method for breast cancer. However, many
      metabolic biomarkers are difficult to replicate among studies. METHODS: We
      propose that higher-order functional representation of metabolomics data, such as
      pathway-based metabolomic features, can be used as robust biomarkers for breast
      cancer. Towards this, we have developed a new computational method that uses
      personalized pathway dysregulation scores for disease diagnosis. We applied this
      method to predict breast cancer occurrence, in combination with correlation
      feature selection (CFS) and classification methods. RESULTS: The resulting all
      stage and early-stage diagnosis models are highly accurate in two sets of testing
      blood samples, with average AUCs (Area Under the Curve, a receiver operating
      characteristic curve) of 0.968 and 0.934, sensitivities of 0.946 and 0.954, and
      specificities of 0.934 and 0.918. These two metabolomics-based pathway models are
      further validated by RNA-Seq-based TCGA (The Cancer Genome Atlas) breast cancer
      data, with AUCs of 0.995 and 0.993. Moreover, important metabolic pathways, such
      as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate
      pathway, are revealed as critical biological pathways for early diagnosis of
      breast cancer. CONCLUSIONS: We have successfully developed a new type of pathway
      based model to study metabolomics data for disease diagnosis. Applying this
      method to blood-based breast cancer metabolomics data, we have discovered crucial
      metabolic pathway signatures for breast cancer diagnosis, especially early
      diagnosis. Further, this modeling approach may be generalized to other omics data
      types for disease diagnosis.

PMID- 27036110
TI  - The serine protease prostasin (PRSS8) is a potential biomarker for early
      detection of ovarian cancer.
AB  - BACKGROUND: Ovarian cancer (OVC) is the deadliest of all gynecologic cancers,
      primarily as a consequence of asymptomatic progression. The complex nature of OVC
      creates challenges for early detection, and there is a lack of specific and
      sensitive biomarkers suitable for screening and detecting early stage OVC.
      METHODS: Potential OVC biomarkers were identified by bioinformatic analysis.
      Candidates were further screened for differential expression in a library of OVC
      cell lines. OVC-specific overexpression of a candidate gene, PRSS8, which encodes
      prostasin, was confirmed against 18 major human cancer types from 390 cancer
      samples by qRT-PCR. PRSS8 expression profiles stratified by OVC tumor stage-,
      grade- and subtype were generated using cDNA samples from 159 OVC samples. Cell
      specific expression and localization of prostasin was determined by
      immunohistological tissue array analysis of more than 500 normal, benign, and
      cancerous ovarian tissues. The presence of prostasin in normal, benign, and OVC
      serum samples was also determined. RESULTS: Gene expression analysis indicated
      that PRSS8 was expressed in OVC at levels more than 100 fold greater than found
      in normal or benign ovarian lesions. This overexpression signature was found in
      early stages of OVC and was maintained in higher stages and grades of OVC. The
      PRSS8 overexpression signature was specific for OVC and urinary bladder cancer
      among 18 human cancer types. The majority of ovarian cell lines overexpressed
      PRSS8. In situ hybridization and histopathology studies of OVC tissues indicated
      that overexpression of prostasin was largely localized to tumor epithelium and
      was absent in neighboring stroma. Significantly higher levels of prostasin were
      found in early stage OVC serum samples compared to benign ovarian and normal
      donor samples. CONCLUSIONS: The abundant amounts of secreted prostasin found in
      sera of early stage OVC can potentially be used as a minimally invasive screening
      biomarker for early stage OVC. Overexpression of PRSS8 mRNA and high levels of
      prostasin in multiple subtypes of early stage ovarian tumors may provide clinical
      biomarkers for early detection of OVC, which can potentially be used with CA125
      and HE4.

PMID- 27036111
TI  - Acthar gel in the treatment of nephrotic syndrome: a multicenter retrospective
      case series.
AB  - BACKGROUND: Current first-line anti-proteinuric treatments for nephrotic syndrome
      (NS) do not produce an effective response in all patients and are not tolerated
      by some patients. Additional effective and tolerable treatment options in NS are
      strongly needed. This retrospective case series is the largest to date to examine
      Acthar gel (adrenocorticotropic hormone, ACTH) in patients with varied-etiology
      NS. METHODS: This multicenter retrospective case series included adult patients
      with NS (N = 44) treated with Acthar gel at 6 clinical practices. NS etiologies
      included idiopathic focal segmental glomerulosclerosis (FSGS, 15), idiopathic
      membranous nephropathy (iMN, 11), IgA nephropathy (IgAN, 5), diabetic nephropathy
      (DN, 4), systemic lupus erythematosus class V membranous lupus nephritis (MLN,
      2), minimal change disease (MCD, 2), membranoproliferative glomerulonephritis
      (MPGN, 1), fibrillary glomerulonephritis (FGN, 1), and unbiopsied NS (3).
      Proteinuria response was assessed as percent reduction from baseline and percent
      of patients meeting complete remission (final proteinuria <500 mg/d), partial
      remission (>=50 % reduction in proteinuria from baseline and final proteinuria
      500-3500 mg/d), clinical response (>=30 % reduction in proteinuria from baseline
      that did not meet criteria for complete or partial remission), and no response
      (failed to meet remission or clinical response criteria) following Acthar gel
      therapy. Safety and tolerability were examined using adverse event (AE) frequency
      reported by patients or treating nephrologists and frequency of early
      discontinuation of treatment due to AEs. RESULTS: 68.2 % (30/44) of patients had
      received prior NS treatment with immunosuppressive or cytotoxic therapies. Thirty
      seven patients completed Acthar gel treatment. Seven patients (15.9 %) had early
      termination due to AEs, including weight gain (2), hypertension (2), edema (1),
      fatigue (1), seizures (1) and for reasons not stated (2). Proteinuria reduction
      >=30 % was shown in 81.1 % (30/37) of patients and 62.2 % (23/37) showed >=50 %
      proteinuria reduction. Proteinuria responses were greatest in MCD (n = 2/2
      complete remission), MLN (n = 2/2 partial remission), MPGN (n = 1/1 partial
      remission), FSGS (n = 12/15 [80.0 %] partial remission or clinical response), and
      iMN (n = 8/11 [72.7 %] complete remission, partial remission, or clinical
      response). CONCLUSIONS: Acthar gel may meet an important treatment need in
      patients with treatment-resistant NS in response to first-line therapies,
      patients unable to tolerate first-line therapies, and in patients with advanced
      disease.

PMID- 27036112
TI  - A randomized clinical trial to determine the effectiveness of CO-oximetry and
      anti-smoking brief advice in a cohort of kidney transplant patients who smoke:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: The cardiovascular risk in renal transplant patients is increased in
      patients who continue to smoke after transplantation. The aim of the study is to
      measure the effectiveness of exhaled carbon monoxide (CO) measurement plus brief
      advisory sessions, in comparison to brief advice, to reduce smoking exposure and
      smoking behavior in kidney transplant recipients who smoke. The effectiveness
      will be measured by: (1) abandonment of smoking, (2) increase in motivation to
      stop smoking, and (3) reduction in the number of cigarettes smoked per day.
      METHODS/DESIGN:  DESIGN: a randomized, controlled, open clinical trial with
      blinded evaluation. SCOPE: A Coruna Hospital (Spain), reference to renal
      transplantation in the period 2012-2015. INCLUSION CRITERIA: renal transplant
      patients who smoke in the precontemplation, contemplation or preparation stages
      according to the Prochaska and DiClemente's Stages of Change model, and who give
      their consent to participate. EXCLUSION CRITERIA: smokers attempting to stop
      smoking, patients with terminal illness or mental disability that prevents them
      from participating. RANDOMIZATION: patients will be randomized to the control
      group (brief advisory session) or the intervention group (brief advisory session
      plus measuring exhaled CO). The sample target size is n = 112, with 56 patients
      in each group. Allowing for up to 10 % loss to follow-up, this would provide 80 %
      power to detect a 13 % difference in attempting to give up smoking outcomes at a
      two-tailed significance level of 5 %. MEASUREMENTS: sociodemographic
      characteristics, cardiovascular risk factors, treatment, rejection episodes,
      infections, self-reported smoking habit, drug use, level of dependence (the
      Fagerstrom test), stage of change (Prochaska and DiClemente's Stages of Change
      model), and motivation to giving up smoking (the Richmond test). RESPONSE: the
      effectiveness will be evaluated every 3, 6, 9 and 12 months as: pattern of
      tobacco use (self-reported tobacco use), smoking cessation rates, carbon monoxide
      (CO) levels in exhaled air measured by CO-oximetry, urinary cotinine tests,
      nicotine dependence (Fagerstrom test), motivational stages of change (Prochaska
      and DiClemente's stages) and motivation to stop smoking (the Richmond test).
      ANALYSIS: descriptive statistics and linear/logistic multiple regression models
      will be performed. Clinical relevance will be measured as relative risk
      reduction, absolute risk reduction and the number needed to treat. ETHICS:
      informed consent of the patients and Ethical Review Board was obtained (code
      2011/061). DISCUSSION: Tobacco is a modifiable risk factor that increase the risk
      of morbidity and mortality in kidney transplant recipients. If effectiveness of
      CO-oximetry is confirmed to reduce tobacco exposure, we would have an
      intervention that is easy to use, low cost and with great implications about
      cardiovascular risk prevention in these patients. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN16615772 . EudraCT number: 2015-002009-12.

PMID- 27036113
TI  - Can early weight loss, eating behaviors and socioeconomic factors predict
      successful weight loss at 12- and 24-months in adolescents with obesity and
      insulin resistance participating in a randomised controlled trial?
AB  - BACKGROUND: Lifestyle interventions in adolescents with obesity can result in
      weight loss following active intervention but individual responses vary widely.
      This study aimed to identify predictors of weight loss at 12- and 24-months in
      adolescents with obesity and clinical features of insulin resistance. METHODS:
      Adolescents (n = 111, 66 girls, aged 10-17 years) were participants in a
      randomised controlled trial, the RESIST study, examining the effects of two diets
      differing in macronutrient content on insulin sensitivity. Eighty-five completed
      the 12-month program and 24-month follow-up data were available for 42
      adolescents. Change in weight was determined by BMI expressed as a percentage of
      the 95th percentile (BMI95). The study physician collected socioeconomic data at
      baseline. Physical activity and screen time, and psychological dimensions of
      eating behavior were self-reported using the validated CLASS and EPI-C
      questionnaires, respectively. Stepwise multiple regressions were conducted to
      identify models that best predicted change in BMI95 at 12- and 24-months.
      RESULTS: Mean BMI95 was reduced at 12-months compared with baseline (mean
      difference [MD] +/- SE: -6.9 +/- 1.0, P < 0.001) but adolescents had significant
      re-gain from 12- to 24-months (MD +/- SE: 3.7 +/- 1.5, P = 0.017). Participants
      who achieved greater 12-month weight loss had: greater 3-month weight loss, a
      father with a higher education, lower baseline external eating and parental
      pressure to eat scores and two parents living at home. Participants who achieved
      greater 24-month weight loss had: greater 12-month weight loss and a lower
      baseline emotional eating score. CONCLUSIONS: Early weight loss is consistently
      identified as a strong predictor of long-term weight loss. This could be because
      early weight loss identifies those more motivated and engaged individuals.
      Patients who have baseline factors predictive of long-term weight loss failure
      may benefit from additional support during the intervention. Additionally, if a
      patient does not achieve early weight loss, further support or transition to an
      alternate intervention where they may have increased success may be considered.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registration Number
      (ACTRN) 12608000416392
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071.

PMID- 27036114
TI  - Surveillance for Eurasian-origin and intercontinental reassortant highly
      pathogenic influenza A viruses in Alaska, spring and summer 2015.
AB  - BACKGROUND: Eurasian-origin and intercontinental reassortant highly pathogenic
      (HP) influenza A viruses (IAVs) were first detected in North America in wild,
      captive, and domestic birds during November-December 2014. Detections of HP
      viruses in wild birds in the contiguous United States and southern Canadian
      provinces continued into winter and spring of 2015 raising concerns that
      migratory birds could potentially disperse viruses to more northerly breeding
      areas where they could be maintained to eventually seed future poultry outbreaks.
      RESULTS: We sampled 1,129 wild birds on the Yukon-Kuskokwim Delta, Alaska, one of
      the largest breeding areas for waterfowl in North America, during spring and
      summer of 2015 to test for Eurasian lineage and intercontinental reassortant HP
      H5 IAVs and potential progeny viruses. We did not detect HP IAVs in our sample
      collection from western Alaska; however, we isolated five low pathogenic (LP)
      viruses. Four isolates were of the H6N1 (n = 2), H6N2, and H9N2 combined subtypes
      whereas the fifth isolate was a mixed infection that included H3 and N7 gene
      segments. Genetic characterization of these five LP IAVs isolated from cackling
      (Branta hutchinsii; n = 2) and greater white-fronted geese (Anser albifrons; n =
      3), revealed three viral gene segments sharing high nucleotide identity with HP
      H5 viruses recently detected in North America. Additionally, one of the five
      isolates was comprised of multiple Eurasian lineage gene segments. CONCLUSIONS:
      Our results did not provide direct evidence for circulation of HP IAVs in the
      Yukon-Kuskokwim Delta region of Alaska during spring and summer of 2015.
      Prevalence and genetic characteristics of LP IAVs during the sampling period are
      concordant with previous findings of relatively low viral prevalence in geese
      during spring, non-detection of IAVs in geese during summer, and evidence for
      intercontinental exchange of viruses in western Alaska.

PMID- 27036115
TI  - Hepatitis C testing in substance use disorder treatment: the role of program
      managers in adoption of testing services.
AB  - BACKGROUND: Health care organizations do not adopt best practices as often or
      quickly as they merit. This gap in the integration of best practices into routine
      practice remains a significant public health concern. The role of program
      managers in the adoption of best practices has seldom been investigated. METHODS:
      We investigated the association between characteristics of program managers and
      the adoption of hepatitis C virus (HCV) testing services in opioid treatment
      programs (OTPs). Data came from the 2005 (n = 187) and 2011 (n = 196) National
      Drug Abuse Treatment System Survey (NDATSS). We used multivariate regression
      models to examine correlates of the adoption of HCV testing. We included
      covariates describing program manager characteristics, such as their
      race/ethnicity, education, and their sources of information about developments in
      the field of substance use disorder treatment. We also controlled for
      characteristics of OTPs and the client populations they serve. RESULTS: Program
      managers were predominantly white and female. A large proportion of program
      managers had post-graduate education. Program managers expressed strong support
      for preventive services, but they reported making limited use of available
      sources of information about developments in the field of substance use disorder
      (SUD) treatment. The provision of any HCV testing (either on-site or off-site) in
      OTPs was positively associated with the extent to which a program manager was
      supportive of preventive services. Among OTPs offering any HCV testing to their
      clients, on-site HCV testing was more common among programs with an African
      American manager. It was also more common when program managers relied on a
      variety of information sources about developments in SUD treatment. CONCLUSIONS:
      Various characteristics of program managers are associated with the adoption of
      HCV testing in OTPs. Promoting diversity among program managers, and increasing
      managers' access to information about developments in SUD treatment, may help
      foster the adoption of best practices.

PMID- 27036116
TI  - The influence of gender and other patient characteristics on health care-seeking
      behaviour: a QUALICOPC study.
AB  - BACKGROUND: Canadians' health care-seeking behaviour for physical and mental
      health issues was examined using the international Quality and Cost of Primary
      Care (QUALICOPC) survey that was conducted in 2013 in Canada. METHOD: This study
      used the cross-sectional Patient Experiences Survey collected from 7260 patients
      in 759 practices across 10 Canadian provinces as part of the QUALICOPC study. A
      Responsive Care Scale (RCS) was constructed to reflect the degree of health care
      seeking behaviour across 11 health conditions. Using several patient
      characteristics as independent variables, four multiple regression analyses were
      conducted. RESULTS: Patients' self-reports indicated that there were gender
      differences in health care-seeking behaviour, with women reporting they visited
      their primary care provider to a greater extent than did men for both physical
      and mental health concerns. Overall, patients were less likely to seek care for
      mental health concerns in comparison to physical health concerns. For both women
      and men, the results of the regressions indicated that age, illness prevention,
      trust in physicians and chronic conditions were important factors when explaining
      health care-seeking behaviours for mental health concerns. CONCLUSION: This study
      confirms the gender differences in health care-seeking behaviour advances
      previous research by exploring in detail the variables predicting differences in
      health care-seeking behaviour for men and women. The variables were better
      predictors of health care-seeking behaviour in response to mental health concerns
      than physical health concerns, likely reflecting greater variation among those
      seeking mental health care. This study has implications for those working to
      improve barriers to health care access by identifying those more likely to engage
      in health care-seeking behaviours and the variables predicting health care
      seeking. Consequently, those who are not accessing primary care can be targeted
      and policies can be developed and put in place to promote their health care
      seeking behavior.

PMID- 27036117
TI  - Level of arterial ligation in sigmoid colon and rectal cancer surgery.
AB  - BACKGROUND: Curative resection of sigmoid colon and rectal cancer includes "high
      tie" of the inferior mesenteric artery (IMA). However, IMA ligation compromises
      blood flow to the anastomosis, which may increase the leakage rate, and it is
      unclear whether this confers a survival advantage. Accordingly, the IMA may be
      ligated at a point just below the origin of the left colic artery (LCA) "low tie"
      combined with lymph node dissection (LND) around the origin of the IMA (low tie
      with LND). However, no study has investigated the detailed prognostic results
      between "high tie" and "low tie with LND." The aim of this study was to assess
      the utility of "low tie with LND" on survival in patients with sigmoid colon or
      rectal cancer. METHODS: A total of 189 sigmoid colon or rectal cancer patients
      who underwent curative operation from 1997 to 2007 were enrolled in this study.
      The patient's medical records were reviewed to obtain clinicopathological
      information. Overall survival (OS) and relapse-free survival (RFS) rates were
      calculated using the Kaplan-Meier method, with differences assessed using log
      rank test. RESULTS: Forty-two and 147 patients were ligated at the origin of the
      IMA (high tie) and just below the origin of the LCA combined with LND around the
      origin of the IMA (low tie with LND), respectively. No significant differences
      were observed in the complication rate and OS and RFS rates in the two groups.
      Further, no significant difference was observed in the OS and RFS rates in the
      lymph node-positive cases in the two groups. CONCLUSIONS: "Low tie with LND" is
      anatomically less invasive and is not inferior to "high tie" with prognostic
      point of view.

PMID- 27036118
TI  - Human embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen
      induced arthritis by inducing host-derived indoleamine 2,3 dioxygenase.
AB  - BACKGROUND: The immunosuppressive and anti-inflammatory properties of mesenchymal
      stromal cells (MSC) have prompted their therapeutic application in several
      autoimmune diseases, including rheumatoid arthritis. Adult MSC are finite and
      their clinical use is restricted by the need for long-term expansion protocols
      that can lead to genomic instability. Inhibition of Smad2/3 signaling in human
      pluripotent stem cells (hPSC) provides an infinite source of MSC that match the
      phenotype and functional properties of adult MSC. Here, we test the therapeutic
      potential of hPSC-MSC of embryonic origin (embryonic stem cell-derived
      mesenchymal stromal cells, hESC-MSC) in the experimental model of collagen
      induced arthritis (CIA). METHODS: CIA was induced in DBA/1 mice by immunization
      with type II collagen (CII) in Complete Freund's Adjuvant (CFA). Mice were
      treated with either a single dose (10(6) cells/mouse) of hESC-MSC on the day of
      immunization (prophylaxis) or with three doses of hESC-MSC every other day
      starting on the day of arthritis onset (therapy). Arthritis severity was
      evaluated daily for six weeks and ten days, respectively. Frequency of Treg
      (FoxP3(+)), Th1 (IFNgamma(+)) and Th17 (IL17(+)) CD4(+) T cells in inguinal lymph
      nodes (ILN) was quantified by flow cytometry. Serum levels of anti-CII antibodies
      were determined by ELISA. Detection of hESC-MSC and quantification of murine and
      human indoleamine 2,3 dioxygenase (IDO1) expression was performed by quantitative
      real-time PCR. Statistical differences were analyzed by ANOVA and the Mann
      Whitney U test. RESULTS: Administration of hESC-MSC to mice with established
      arthritis reduced disease severity compared to control-treated mice. Analysis of
      CD4 T cell populations in treated mice showed an increase in FoxP3(+) Treg and
      IFNgamma(+) Th1 cells but not in Th17 cells in the ILN. Anti-CII antibody levels
      were not affected by treatment. Migration of hESC-MSC to the ILN in treated mice
      was associated with the induction of murine IDO1. CONCLUSION: Treatment with hESC
      MSC ameliorates CIA by inducing IFNgamma(+) Th1 cells and IDO1 in the host. Thus,
      hESC-MSC can provide an infinite cellular source for treatment of rheumatoid
      arthritis.

PMID- 27036119
TI  - Nemo-like kinase as a negative regulator of nuclear receptor Nurr1 gene
      transcription in prostate cancer.
AB  - BACKGROUND: Nurr1, a member of the orphan receptor family, plays an important
      role in several types of cancer. Our previous work demonstrated that increased
      expression of Nurr1 plays a significant role in the initiation and progression of
      prostate cancer (PCa), though the mechanisms for regulation of Nurr1 expression
      remain unknown. In this study, we investigated the hypothesis that Nemo-like
      kinase (NLK) is a key regulator of Nurr1 expression in PCa. METHODS:
      Immunohistochemistry and Western blot analysis were used to evaluate levels of
      NLK and Nurr1 in prostatic tissues and cell lines. The effects of overexpression
      or knockdown of Nurr1 were evaluated in PCa cells through use of PCR, Western
      blots and promoter reporter assays. The role of Nurr1 promoter cis element was
      studied by creation of two mutant Nurr1 promoter luciferase constructs, one with
      a mutated NF-kappaB binding site and one with a mutated CREB binding site. In
      addition, three specific inhibitors were used to investigate the roles of these
      proteins in transcriptional activation of Nurr1, including BAY 11-7082 (NF-kappaB
      inhibitor), KG-501 (CREB inhibitor) and ICG-001 (CREB binding protein, CBP,
      inhibitor). The function of CBP in NLK-mediated regulation of Nurr1 expression
      was investigated using immunofluorescence, co-immunoprecipitation (Co-IP) and
      chromatin immunoprecipitation assays (ChIPs). RESULTS: NLK expression was
      inversely correlated with Nurr1 expression in prostate cancer tissues and cell
      lines. Overexpression of NLK suppressed Nurr1 promoter activity, leading to
      downregulation of Nurr1 expression. In contrast, knockdown of NLK demonstrated
      opposite results, leading to upregulation of Nurr1. When compared with the wild
      type Nurr1 promoter, mutation of NF-kappaB- and CREB-binding sites of the Nurr1
      promoter region significantly reduced the upregulation of Nurr1 induced by
      knockdown of NLK in LNCaP cells; treatment with inhibitors of CREB, CBP and NF
      kappaB led to similar results. We also found that NLK directly interacts with
      CBP, that knockdown of NLK significantly increases the recruitment of CBP to both
      NF-kappaB- and CREB-binding sites, and that regulation of NLK on Nurr1 expression
      is abrogated by knockdown of CBP. CONCLUSIONS: Our results suggest that NLK
      inhibits transcriptional activation of Nurr1 gene by impeding CBP's role as a co
      activator of NF-kappaB and CREB in prostate cancer.

PMID- 27036120
TI  - Insertion torque recordings for the diagnosis of contact between orthodontic mini
      implants and dental roots: a systematic review.
AB  - BACKGROUND: Most orthodontic mini-implants (OMIs) are inserted between dental
      roots. The prevalence of contacting these structures is high. Such contacts can
      cause permanent root damage and implant instability. Increased torque levels
      during implant insertion (the index test) could be a more accurate and immediate
      measure for diagnosing implant-root contact (the target condition) than
      radiographs (the reference standard) and could ultimately lead to a reduction or
      elimination of X-ray exposure. To address this issue, we asked three questions:
      (1) whether OMIs with root contact had higher insertion torque values than those
      without, (2) what is the accuracy of the index test compared with the reference
      standard to diagnose the target condition and what are the adverse effects of the
      index test, and (3) whether intermediate torque values have clinical diagnostic
      utility. METHODS: Methods were conducted according to our published protocol,
      which was based on the PRISMA-P 2015 statement. We applied broad spectrum
      eligibility criteria that included randomized and non-randomized studies on
      clinical, animal, and cadaver models. Not including such models would be
      unethical because it could slow down knowledge creation on the adverse effects of
      implant insertion. We conducted searches in more than 40 electronic databases
      including MEDLINE and 10 journals were hand-searched. Grey literature and
      reference lists were also searched. All research procedures were conducted
      independently by three reviewers. Authors of selected studies were contacted to
      obtain additional information. Outcomes on the three different research models
      were analysed separately. Systematic error was assessed with the Cochrane 'Risk
      of bias tool' for non-randomized studies. RESULTS: One clinical, two animal, and
      two cadaver studies fulfilled the eligibility criteria of the first research
      question. All studies and subgroups demonstrated higher insertion torque values
      for OMIs with the target condition than those without. Mean differences (MD)
      between these effect estimates were statistically significant in one beagle model
      (MD, 4.64; 95 % CI, 3.50 to 5.79) and three subgroups of cadaver studies (MD,
      2.70; 95 % CI, 1.42 to 3.98) (MD, 3.97; 95 % CI, 2.17 to 5.78) (MD, 0.93; 95 %
      CI, 0.67 to 1.20). Highest mean differences were identified in most self-drilling
      compared with pre-drilling groups. Clinical heterogeneity between studies was
      high, and many items were underreported. All studies except one cadaver study
      scored at least one domain as 'serious risk' of bias. No studies addressed the
      second research question. One cadaver study addressed the third question which
      showed the importance of recording torque levels during the entire implant
      insertion process. Responses of contacted authors were helpful, but often
      difficult to obtain. Implants fractured in one animal and in one cadaver model.
      CONCLUSIONS: All eligible studies scored higher insertion torque values for
      implants with root contact than those without, but none of these studies assessed
      the diagnostic accuracy of the index test. The inclusion of non-randomized and
      animal and cadaver models in this systematic review provided key findings that
      otherwise would have been wasted. Such studies are important in the context of
      the wide applicability of this test, the high prevalence of the target condition,
      and the underreporting of adverse effects of interventions. A protocol for a
      potential new diagnostic pathway was presented, and the importance of contacting
      authors was addressed. The applicability of the findings should be interpreted in
      the context of underreporting and the many limitations of the included studies.

PMID- 27036121
TI  - Pathological tau deposition in Motor Neurone Disease and frontotemporal lobar
      degeneration associated with TDP-43 proteinopathy.
AB  - It has been suggested that patients with motor neurone disease (MND) and those
      with MND combined with behavioural variant frontotemporal dementia (bvFTD) (ie
      FTD + MND) or with FTD alone might exist on a continuum based on commonalities of
      neuropathology and/or genetic risk. Moreover, it has been reported that both a
      neuronal and a glial cell tauopathy can accompany the TDP-43 proteinopathy in
      patients with motor neurone disease (MND) with cognitive changes, and that the
      tauopathy may be fundamental to disease pathogenesis and clinical phenotype. In
      the present study, we sought to substantiate these latter findings, and test this
      concept of a pathological continuum, in a consecutive series of 41 patients with
      MND, 16 with FTD + MND and 23 with FTD without MND. Paraffin sections of frontal,
      entorhinal, temporal and occipital cortex and hippocampus were immunostained for
      tau pathology using anti-tau antibodies, AT8, pThr(175) and pThr(217), and for
      amyloid beta protein (Abeta) using 4G8 antibody. Twenty four (59 %) patients with
      MND, 7 (44 %) patients with FTD + MND and 10 (43 %) patients with FTD showed
      'significant' tau pathology (ie more than just an isolated neurofibrillary tangle
      or a few neuropil threads in one or more brain regions examined). In most
      instances, this bore the histological characteristics of an Alzheimer's disease
      process involving entorhinal cortex, hippocampus, temporal cortex, frontal cortex
      and occipital cortex in decreasing frequency, accompanied by a deposition of
      Abeta up to Thal phase 3, though 2 patients with MND, and 1 with FTD did show tau
      pathology beyond Braak stage III. Four other patients with MND showed novel
      neuronal tau pathology, within the frontal cortex alone, specifically detected by
      pThr(175) antibody, which was characterised by a fine granular or more clumped
      aggregation of tau without neurofibrillary tangles or neuropil threads. However,
      none of these 4 patients had clinically evident cognitive disorder, and this type
      of tau pathology was not seen in any of the FTD + MND or FTD patients. Finally,
      two patients, one with MND and one with FTD, showed a tau pathology consistent
      with Argyrophilic Grain Disease (AGD). Western blotting and use of 3- and 4
      repeat tau antibodies confirmed the histological interpretation of Alzheimer's
      disease type pathology in all instances except for those patients with
      accompanying AGD where a banding pattern on western blot, and
      immunohistochemistry, confirmed 4-repeat tauopathy. In all 3 patient groups,
      amyloid pathology was more likely to be present in patients dying after 65 years
      of age, and in the presence of APOE epsilon4 allele. We conclude that tau
      pathological changes are equally common amongst patients with MND, FTD + MND and
      FTD though, in most instances, these are limited in extent. In patients with MND,
      when cognitive impairment is present this is most likely due to an
      accompanying/evolving (coincidental) Alzheimer's disease process or, as in a
      single case, Dementia with Lewy bodies, within the cerebral cortex rather than as
      a result of TDP-43 proteinopathy. Conversely, in FTD and FTD + MND dementia is
      more likely to be associated with TDP-43 proteinopathy than tau. Hence, present
      study shows no progression in severity of (tau) pathology from MND through FTD +
      MND to FTD, and does not support the concept of these conditions forming a
      continuum of clinical or pathological change. 

PMID- 27036122
TI  - Lurasidone: an antipsychotic with antidepressant effects in bipolar depression?
AB  - OBJECTIVE: Lurasidone is a new serotonin-dopamine antagonist atypical
      antipsychotic which also appears to be effective in bipolar depression. This
      paper will briefly review the evidence concerning lurasidone. CONCLUSIONS:
      Lurasidone is an antagonist at dopamine D2, serotonin 5-HT2 and 5-HT7, and
      partial agonist at 5HT1a receptors; it has no anticholinergic or antihistaminic
      activity. Rapidly absorbed, it has a half-life of 18 +/- 7 hours, will reach
      steady state in five days and is taken at night with food (absorption is halved
      on an empty stomach). It is hepatically metabolised with some potential for
      interactions. Lurasidone is an effective antipsychotic in acute schizophrenia,
      and non-inferior to quetiapine but not risperidone in 12-month studies.
      Lurasidone may cause mild sedation, nausea, agitation, insomnia and akathisia
      (especially at initiation). Risks for weight gain, hyperprolactinaemia and QTc
      prolongation are low. Lurasidone has demonstrated antidepressant efficacy both as
      monotherapy and in addition to lithium or valproate in bipolar depression, of a
      comparable degree to that seen with the combination of olanzapine and fluoxetine.
      Lurasidone appears to be a "metabolically-friendly" antipsychotic for
      schizophrenia where weight gain and hyperprolactinaemia are of concern, and may
      also prove useful in bipolar depression (although not approved for this condition
      in Australia).

PMID- 27036124
TI  - Structure of Gremlin-1 and analysis of its interaction with BMP-2.
AB  - Bone morphogenetic protein 2 (BMP-2) is a member of the transforming growth
      factor-beta (TGF-beta) signalling family and has a very broad biological role in
      development. Its signalling is regulated by many effectors: transmembrane
      proteins, membrane-attached proteins and soluble secreted antagonists such as
      Gremlin-1. Very little is known about the molecular mechanism by which Gremlin-1
      and other DAN (differential screening-selected gene aberrative in neuroblastoma)
      family proteins inhibit BMP signalling. We analysed the interaction of Gremlin-1
      with BMP-2 using a range of biophysical techniques, and used mutagenesis to map
      the binding site on BMP-2. We have also determined the crystal structure of
      Gremlin-1, revealing a similar conserved dimeric structure to that seen in other
      DAN family inhibitors. Measurements using biolayer interferometry (BLI) indicate
      that Gremlin-1 and BMP-2 can form larger complexes, beyond the expected 1:1
      stoichiometry of dimers, forming oligomers that assemble in alternating fashion.
      These results suggest that inhibition of BMP-2 by Gremlin-1 occurs by a mechanism
      that is distinct from other known inhibitors such as Noggin and Chordin and we
      propose a novel model of BMP-2-Gremlin-1 interaction yet not seen among any BMP
      antagonists, and cannot rule out that several different oligomeric states could
      be found, depending on the concentration of the two proteins.

PMID- 27036125
TI  - Disruption of ribosome assembly in yeast blocks cotranscriptional pre-rRNA
      processing and affects the global hierarchy of ribosome biogenesis.
AB  - In higher eukaryotes, pre-rRNA processing occurs almost exclusively post
      transcriptionally. This is not the case in rapidly dividing yeast, as the
      majority of nascent pre-rRNAs are processed cotranscriptionally, with cleavage at
      the A2 site first releasing a pre-40S ribosomal subunit followed by release of a
      pre-60S ribosomal subunit upon transcription termination. Ribosome assembly is
      driven in part by hierarchical association of assembly factors and r-proteins.
      Groups of proteins are thought to associate with pre-ribosomes
      cotranscriptionally during early assembly steps, whereas others associate later,
      after transcription is completed. Here we describe a previously uncharacterized
      phenotype observed upon disruption of ribosome assembly, in which normally late
      binding proteins associate earlier, with pre-ribosomes containing 35S pre-rRNA.
      As previously observed by many other groups, we show that disruption of 60S
      subunit biogenesis results in increased amounts of 35S pre-rRNA, suggesting that
      a greater fraction of pre-rRNAs are processed post-transcriptionally.
      Surprisingly, we found that early pre-ribosomes containing 35S pre-rRNA also
      contain proteins previously thought to only associate with pre-ribosomes after
      early pre-rRNA processing steps have separated maturation of the two subunits. We
      believe the shift to post-transcriptional processing is ultimately due to
      decreased cellular division upon disruption of ribosome assembly. When cells are
      grown under stress or to high density, a greater fraction of pre-rRNAs are
      processed post-transcriptionally and follow an alternative processing pathway.
      Together, these results affirm the principle that ribosome assembly occurs
      through different, parallel assembly pathways and suggest that there is a kinetic
      foot-race between the formation of protein binding sites and pre-rRNA processing
      events.

PMID- 27036123
TI  - Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals
      an exonic damaging variant in ANGPTL4 determining fasting TG levels.
AB  - BACKGROUND: So far, more than 170 loci have been associated with circulating
      lipid levels through genome-wide association studies (GWAS). These associations
      are largely driven by common variants, their function is often not known, and
      many are likely to be markers for the causal variants. In this study we aimed to
      identify more new rare and low-frequency functional variants associated with
      circulating lipid levels. METHODS: We used the 1000 Genomes Project as a
      reference panel for the imputations of GWAS data from ~60 000 individuals in the
      discovery stage and ~90 000 samples in the replication stage. RESULTS: Our study
      resulted in the identification of five new associations with circulating lipid
      levels at four loci. All four loci are within genes that can be linked
      biologically to lipid metabolism. One of the variants, rs116843064, is a damaging
      missense variant within the ANGPTL4 gene. CONCLUSIONS: This study illustrates
      that GWAS with high-scale imputation may still help us unravel the biological
      mechanism behind circulating lipid levels.

PMID- 27036127
TI  - High-potency cannabis increases the risk of psychosis.

PMID- 27036126
TI  - Ascorbylperoxide Contaminating Parenteral Nutrition Is Associated With
      Bronchopulmonary Dysplasia or Death in Extremely Preterm Infants.
AB  - BACKGROUND: Ascorbylperoxide (AscOOH) is a hydrogen peroxide-dependent by-product
      of ascorbic acid that contaminates parenteral nutrition. In a guinea pig model,
      it caused oxidized redox potential, increased apoptosis, and decreased
      alveolarization. AscOOH detoxification is carried out by glutathione peroxidase
      (GPX). We hypothesize that extremely preterm infants have limited capacity for
      AscOOH detoxification. Our objective was to determine if there is an association
      between an early level of urinary AscOOH and later development of
      bronchopulmonary dysplasia (BPD) or death. MATERIALS AND METHODS: This
      prospective cohort study included 51 infants at <29 weeks of gestation. Baseline
      clinical characteristics and clinical outcomes data were collected. Urine samples
      were collected on days 3, 5, and 7 of life for urinary AscOOH. Blood samples on
      day 7 were collected for total plasma glutathione, GPX, and glutathione
      reductase. chi2, Student's t test, Spearman correlation ( r), linear regression
      (adjusted r2), and repeated-measure analysis of variance were used as
      appropriate. P < .05 was considered significant. RESULTS: Urinary AscOOH
      increased over time ( P = .001) and was higher in infants who later developed BPD
      or died ( P = .037). Compared with adults and full-term infants, total plasma
      glutathione concentration was low (median, 1.02 umol/L; 25th-75th percentiles,
      0.49-1.76 umol/L), whereas GPX and glutathione reductase activities were
      sufficient (3.98 +/- 1.25 and 0.36 +/- 0.01 nmol/min/mg of protein,
      respectively). CONCLUSION: Extremely preterm infants have low glutathione levels,
      which limit their capacity to detoxify AscOOH. Higher first-week urinary AscOOH
      levels are associated with an increased incidence of BPD or death.

PMID- 27036129
TI  - From promise to application: root traits for enhanced nutrient capture in rice
      breeding.
AB  - Improving nutrient uptake is an objective in crop breeding, especially in
      tropical areas where infertile soils dominate and farmers may not have the
      resources to improve soil fertility through fertilizer application. Scientific
      endeavors to understand the genetic basis of nutrient acquisition have mostly
      followed reverse genetic approaches. This has undoubtedly led to improved
      understanding of basic principles in root development and nutrient transport.
      However, little evidence suggests that the genes identified are actively utilized
      in breeding programs, and the bottleneck has been the failure to establish links
      between allelic variation for identified genes and performance in the field.
      Screening experiments typically reveal large genotypic variation in performance
      under nutrient deficiency, strongly suggesting the presence of superior alleles
      for genes controlling root growth and/or nutrient uptake processes. Progress in
      sequencing technology has enabled characterizations of allelic variation across
      whole genomes and an international effort has recently culminated in the
      sequencing of 3000 rice genomes from the International Rice Research Institute
      genebank. Queries of the 3000 rice sequence database offer immediate
      possibilities to assess the extent to which allelic variation exists for
      candidate genes. By selecting subsets of accessions, allelic effects can be
      tested, diagnostic markers developed, and new donors identified. Technological
      and conceptual advances in phenotyping of root traits offer improved
      possibilities to assure that trait-allele associations are established in ways
      that link to field performance. Genotype-to-phenotype relationships can thus be
      predicted and tested with unprecedented precision, facilitating the discovery and
      transfer of beneficial nutrition-related alleles and associated markers into
      existing breeding pipelines.

PMID- 27036128
TI  - Challenges to Healthy Eating Practices: A Qualitative Study of Non-Hispanic Black
      Men Living With Diabetes.
AB  - PURPOSE: The purpose of this study was to explore current dietary practices and
      perceived barriers to healthy eating in non-Hispanic black men with type 2
      diabetes. METHODS: Four 90-minute focus groups held in September and October 2011
      were led by a trained moderator with a written guide to facilitate discussion on
      dietary practices and barriers to healthy eating. Participants were recruited
      from the diabetes database at a public safety-net health system in Jefferson
      County, Alabama. Two-independent reviewers performed content analysis to identify
      major themes using a combined deductive and inductive approach. RESULTS: There
      were 34 male participants aged 18 years and older. Mean years living with
      diabetes was 9.6 +/- 5.9. Sixty-two percent of participants perceived themselves
      to be in fair or poor health. Participants' self-reported eating practices did
      not always relate to hunger. Internal cues to eat included habit and response to
      emotions, and external cues to eat included media messaging, medication regimens,
      and work schedules. Men identified multiple barriers to healthy eating including
      hard-to-break habits, limited resources and availability of food at home and in
      neighborhood grocery stores, and perceived poor communication with health care
      professionals. CONCLUSION: Non-Hispanic black men acknowledged the importance of
      healthy eating as part of diabetes self-management but reported various internal
      and external challenges that present barriers to healthy eating. Tailored
      strategies to overcome barriers to healthy eating among non-Hispanic black men
      should be developed and tested for their impact on diabetes self-management.

PMID- 27036130
TI  - It's not just a knee, but a whole life: A qualitative descriptive study on
      patients' experiences of living with knee osteoarthritis and their expectations
      for knee arthroplasty.
AB  - AIM: Knee arthroplasties are an increasingly common treatment for osteoarthritis
      (OA) and the main indication is pain. Previous research states, however, that 15
      20% of the operated patients are dissatisfied and 20-30% have persistent pain
      after surgery. This study is aimed at describing patients' experiences of living
      with knee OA when scheduled for surgery and further their expectations for future
      life after surgery. METHODS: We interviewed 12 patients with knee OA scheduled
      for arthroplasty, using semi-structured qualitative interviews. The interviews
      were recorded and transcribed verbatim and analyzed using qualitative thematic
      analysis. FINDINGS: Three categories were formulated with an overriding theme:
      "It's not just a knee, but a whole life." The three categories were "Change from
      their earlier lives," "Coping with knee problems," and "Ultimate decision to
      undergo surgery." The main finding was that knee OA affects the whole body and
      self, ultimately affecting the patients' lives on many levels. Further findings
      were that knee OA was considered to be the central focus in the participants'
      lives, which limited their level of activity, their ability to function as
      desired, their quality of life, and their mental well-being. Although surgery was
      considered to be the only solution, the expectations regarding the outcome
      differed. CONCLUSIONS: The participants were forced to change how they previously
      had lived their lives resulting in a feeling of loss. Thus, the experienced loss
      and expectations for future life must be put into the context of the individual's
      own personality and be taken into account when treating individuals with knee OA.
      The experience of living with knee OA largely varies between individuals. This
      mandates that patients' assessment should be considered on individual basis with
      regard to each patient.

PMID- 27036131
TI  - Inhibition of GLI1 Expression by Targeting the CRD-BP-GLI1 mRNA Interaction Using
      a Specific Oligonucleotide.
AB  - The stabilization of glioma-associated oncogene 1 (GLI1) mRNA by coding region
      determinant binding protein (CRD-BP) through the Wnt/beta-catenin signaling
      pathway is implicated in the proliferation of colorectal cancer and basal cell
      carcinoma. Here, we set out to characterize the physical interaction between CRD
      BP and GLI1 mRNA so as to find inhibitors for such interaction. Studies using CRD
      BP variants with a point mutation in the GXXG motif at each KH domain showed that
      KH1 and KH2 domain are critical for the binding of GLI1 RNA. The smallest region
      of GLI1 RNA binding to CRD-BP was mapped to nucleotides (nts) 320-380. A 37-nt S1
      RNA sense oligonucleotide, containing two distinct stem-loops present in nts 320
      380 of GLI1 RNA, was found to be effective in blocking CRD-BP-GLI1 RNA
      interaction. Studies using various competitor RNAs with modifications to S1 RNA
      oligonucleotide further displayed that both the sequences and the structure of
      the two stem-loops are important for CRD-BP-GLI1 RNA binding. The role of the two
      stem-loop motif in influencing CRD-BP-RNA interaction was further investigated in
      cells. The 2'-O-methyl derivative of the S1 RNA oligonucleotide significantly
      decreased GLI1, c-myc, and CD44 mRNA levels, in a panel of colon and breast
      cancer cells. The results from this study demonstrate the potential importance of
      the two-stem-loop motif as a target region for the inhibition of the CRD-BP-GLI1
      RNA interaction and Hedgehog signaling pathway. Such results pave the way for the
      development of novel inhibitors that act by destabilizing the CRD-BP-GLI1 mRNA
      interaction.

PMID- 27036132
TI  - Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with
      Glutamate Dehydrogenase.
AB  - Cryo-electron microscopy (cryo-EM) methods are now being used to determine
      structures at near-atomic resolution and have great promise in molecular
      pharmacology, especially in the context of mapping the binding of small-molecule
      ligands to protein complexes that display conformational flexibility. We
      illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic
      enzyme that catalyzes the oxidative deamination of glutamate. Dysregulation of
      GDH leads to a variety of metabolic and neurologic disorders. Here, we report
      near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 A to
      3.6 A for GDH complexes, including complexes for which crystal structures are not
      available. We show that the binding of the coenzyme NADH alone or in concert with
      GTP results in a binary mixture in which the enzyme is in either an "open" or
      "closed" state. Whereas the structure of NADH in the active site is similar
      between the open and closed states, it is unexpectedly different at the
      regulatory site. Our studies thus demonstrate that even in instances when there
      is considerable structural information available from X-ray crystallography, cryo
      EM methods can provide useful complementary insights into regulatory mechanisms
      for dynamic protein complexes.

PMID- 27036133
TI  - Stability determinants of bone-borne force-transmitting components in three RME
      hybrid expanders-an in vitro study.
AB  - BACKGROUND: The aim was to test which component [wire arm, connecting abutment
      attachment, and orthodontic mini-implant (OMI)] of the force-transmitting system
      (FTS) in the anterior palate of three commonly used hybrid expanders (HEs; WILMES
      HE, LUDWIG-HE, and WINSAUER-HE) deforms under increasing load. MATERIALS AND
      METHODS: Crude single and double wire arms were tested individually. Non-opening
      of the maxillae halves was simulated in artificial bone blocks with single wire
      and double wire FTS specimens. OMIs were inserted 8mm and underwent 6mm of
      continuous static lateral loading. Deformation angles were measured (X-ray, n =
      6) at 0, 3 and 6mm feed. OMIs and abutments were scan electron microscope (SEM)
      evaluated. RESULTS: After 1.0mm of loading, the single wire arm of all FTS
      deformed between 63.4 (16.5) N and 76.2 (18.4) N, and the double wire arm of
      reinforced FTS (wires positioned 'side by side') deformed after 1.0mm between
      110.0 (18.4) N and 134.8 (22.3) N. The crude single wire resisted 89 (5.1) N
      until plastic deformation, whereas the crude double wire positioned 'on top of
      each other' resisted 438 (21.3) N. At 6mm loading, the reinforced WINSAUER-HE FTS
      withstood a maximum load of 320.9 (31.1) N and the reinforced LUDWIG-HE FTS 19%
      less, both under great deformation of double wires and OMIs. The screw-fixated
      WILMES-HE FTS abutment attachment (overlapping OMI head 34%) detached around
      250N. The bonded WINSAUER-HE and LUDWIG-HE abutment attachments did not detach.
      Nor did the modified bonded plus the modified screw-fixated WILMES-HE abutment
      attachment when overlapping 100%. CONCLUSION: Early OMI and single wire arm
      deformation in HEs are crucial for unsuccessful RME in more mature maxillae.
      Double wire arms should be obligatory. OMIs with inner diameter greater 1.36mm
      are recommended. One hundred per cent overlapping abutment attachments do not
      detach.

PMID- 27036134
TI  - Impacted and transmigrant mandibular canines incidence, aetiology, and treatment:
      a systematic review.
AB  - Background: The incidence of impacted and transmigrant mandibular canines in the
      mandible is not as high as that in the maxilla; consequently, it is more
      difficult to find clinical guidelines derived from sound studies based on large
      patient samples. Objectives: The aim of this systematic review was to summarize
      currently available data pertaining to the incidence and aetiology of impacted
      and transmigrant mandibular canines and the success rates of different treatment
      strategies. Methods: This review was registered with PROSPERO (CRD42014006175)
      and was conducted using PRISMA and CRD (Centre for Reviews and Dissemination,
      University of York) statement. A computerized search of studies published up to
      February 2016 was conducted using the following databases: PubMed, Cochrane
      Central Register of Controlled Clinical trials, ISI Web of Knowledge, and Scopus.
      To identify any relevant publications not included in this list, we manually
      searched the references lists of the selected articles. The Newcastle-Ottawa
      Scale quality assessment tool was utilized to classify the included articles.
      Results: In total, 630 articles were identified after the removal of duplicates.
      A total of 13 studies published between 2001 and 2015 met all the eligibility
      criteria and were included for the final analysis. The sample size in these
      studies ranged from 14 to 112873 teeth, while their methodological quality ranged
      from low to medium. Conclusions: According to the findings from our review, the
      incidence of canine impaction in the mandible ranges from 0.92 to 5.1 per cent,
      while that of canine transmigration ranges from 0.1 to 0.31 per cent. Various
      etiologies may play a role, including odontomes (up to 20 per cent) and lateral
      incisor anomalies (16 per cent). Surgical extraction (89 per cent in some
      studies) and orthodontic traction (20-32 per cent) are the most commonly used
      treatment strategies, with the latter showing a failure rate of 17 per cent in
      two studies.

PMID- 27036135
TI  - Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV
      negative Head and Neck Cancer.
AB  - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is commonly treated with
      radiotherapy, and local failure after treatment remains the major cause of
      disease-related mortality. To date, human papillomavirus (HPV) is the only known
      clinically validated, targetable biomarkers of response to radiation in HNSCC.
      EXPERIMENTAL DESIGN: We performed proteomic and transcriptomic analysis of
      targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in
      vitro, and tested whether pharmacologic blockade of candidate biomarkers
      sensitized cells to radiotherapy. Candidate biomarkers were then investigated in
      several independent cohorts of patients with HNSCC. RESULTS: Increased expression
      of several targets was associated with radioresistance, including FGFR, ERK1,
      EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of
      PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2-M
      arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with
      gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two
      independent cohorts of patients with locally advanced HPV-negative HNSCC,
      PTK2/FAK amplification was highly associated with poorer disease-free survival
      (DFS; P = 0.012 and 0.034). PTK2/FAK mRNA expression was also associated with
      worse DFS (P = 0.03). Moreover, both PTK2/FAK mRNA (P = 0.021) and copy number (P
      = 0.063) were associated with DFS in the Head and Neck Cancer subgroup of The
      Cancer Genome Atlas. CONCLUSIONS: Proteomic analysis identified PTK2/FAK
      overexpression is a biomarker of radioresistance in locally advanced HNSCC, and
      PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK
      inhibition with radiotherapy merit further evaluation as a therapeutic strategy
      for improving local control in HPV-negative HNSCC. Clin Cancer Res; 22(18); 4643
      50. (c)2016 AACR.

PMID- 27036136
TI  - Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated
      Through c-Abl and STAT3 Activation.
AB  - PURPOSE: Visfatin is an adipocytokine involved in cellular metabolism,
      inflammation, and cancer. This study investigated the roles of extracellular
      visfatin in breast cancer, and explored underlying mechanisms in clinical and
      experimental settings. EXPERIMENTAL DESIGN: Associations of serum visfatin with
      clinicopathologic characteristics and patient survival were assessed with Cox
      regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on
      cultured breast cancer cells were examined, followed by in vivo investigation of
      tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were
      used to inhibit c-Abl and STAT3 activation, respectively. RESULTS: Breast cancer
      patients with high serum visfatin levels were associated with advanced tumor
      stage, increased tumor size and lymph node metastasis, and poor survival.
      Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were
      correlated with high serum visfatin levels in patients. Visfatin-promoted in
      vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl
      inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was
      observed in zebrafish xenografted with visfatin-pretreated breast cancer cells.
      Tumor growth and lung metastasis occurred in visfatin-administered mice
      xenografted with breast cancer cells. Tail vein-injected mice with visfatin
      pretreated breast cancer cells showed increased lung metastasis, which was
      suppressed by imatinib. CONCLUSIONS: Serum visfatin levels in breast cancer
      patients reveal potential prognostic values, and our findings that visfatin
      promoted breast cancer through activation of c-Abl and STAT3 may provide an
      important molecular basis for future design of targeted therapies that take into
      account different serum visfatin levels in breast cancer. Clin Cancer Res;
      22(17); 4478-90. (c)2016 AACR.

PMID- 27036137
TI  - Proximal Gastrocnemius Release in the Treatment of Mechanical Metatarsalgia.
AB  - BACKGROUND: Gastrocnemius shortening causes an equinus deformity that may
      clinically manifest in foot disorders, including metatarsalgia. We use this term
      to describe pain localized to the metatarsal heads. The purposes of this
      prospective study were to review the effect of medial gastrocnemius proximal
      release on ankle dorsiflexion and assess the outcome of this technique on pain
      and functional limitations in patients who have mechanical metatarsalgia and
      isolated gastrocnemius shortening. METHODS: We prospectively followed a
      consecutive series of 78 feet in 52 patients with metatarsalgia who had an
      isolated gastrocnemius contracture assessed with the Silfverskiold test. Surgical
      release was evaluated with visual analog scale (VAS) and American Orthopaedic
      Foot & Ankle Society (AOFAS) scales. Ankle dorsiflexion was measured at 1, 3, and
      6 months postoperatively. RESULTS: Preoperative values of VAS and AOFAS were 7.4
      and 46.8, respectively. After 3 months postoperatively, the values were 3.0 and
      81.7, and 6 months after surgery these values were 3.5 and 83.6. No patient
      worsened clinically. There were no major complications. Thirty-six patients
      (69.2%) were completely satisfied with the results of the surgery.
      Preoperatively, ankle dorsiflexion with the knee straight was -17.5 degrees,
      which improved to 2.5 degrees at 6 months postoperatively. CONCLUSION: We believe
      proximal medial gastrocnemius recession is an alternate procedure to treat
      selected patients with mechanical metatarsalgia and gastrocnemius shortening. It
      had acceptable morbidity and cosmetic results. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 27036138
TI  - Long-term Results of Chronic Achilles Tendon Ruptures Repaired With V-Y Tendon
      Plasty and Fascia Turndown.
AB  - BACKGROUND: This study aimed to evaluate the long-term follow-up results of V-Y
      tendon plasty with fascia turndown, for repairing chronic Achilles tendon
      ruptures. METHODS: Seventeen patients (12 males, 5 females), who were diagnosed
      with chronic Achilles tendon rupture and met the inclusion criteria, were
      included in the study. These patients received treatment by means of V-Y tendon
      plasty with fascia turndown from January 1995 to December 2001. Clinical outcomes
      of the patients were assessed by using isokinetic strength testing, questioning
      the patient regarding residual discomfort, pain, or swelling and having the
      ability to perform heel rises and using American Orthopaedic Foot & Ankle
      Society's (AOFAS's) Ankle-Hind Foot Scale score. Mean follow-up duration was 16
      years (13-18 years). RESULTS: Mean time from the injury to operative treatment
      was 7 months. Mean operative defect of Achilles tendon in neutral position after
      debridement was 6 cm. During the follow-up, the mean calf atrophy was 3.4 cm. The
      mean 30 degrees/s plantarflex and 120 degrees/s plantarflex peak torques were 89
      and 45 Nm, respectively. The mean 30 degrees/s plantarflex peak torque deficiency
      was 16%. The mean 120 degrees/s plantarflex peak torque deficiency was 17%. The
      average peak torque deficiency was 17%. The pre- and postoperative mean AOFAS
      Ankle-Hindfoot Scale scores were 64 and 95, respectively. No patient had a
      rerupture. Superficial wound infection was treated with oral antibiotic therapy
      in 2 patients (11%). CONCLUSIONS: The V-Y tendon plasty with fascia turndown for
      repairing chronic Achilles tendon ruptures yielded results comparable with the
      literature regarding clinical outcomes. This method did not require synthetic
      materials for augmentation and was an economic alternative compared to other
      repair methods. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 27036139
TI  - Identification and functional evaluation of the reductases and dehydrogenases
      from Saccharomyces cerevisiae involved in vanillin resistance.
AB  - BACKGROUND: Vanillin, a type of phenolic released during the pre-treatment of
      lignocellulosic materials, is toxic to microorganisms and therefore its presence
      inhibits the fermentation. The vanillin can be reduced to vanillyl alcohol, which
      is much less toxic, by the ethanol producer Saccharomyces cerevisiae. The
      reducing capacity of S. cerevisiae and its vanillin resistance are strongly
      correlated. However, the specific enzymes and their contribution to the vanillin
      reduction are not extensively studied. In our previous work, an evolved vanillin
      resistant strain showed an increased vanillin reduction capacity compared with
      its parent strain. The transcriptome analysis suggested the reductases and
      dehydrogenases of this vanillin resistant strain were up-regulated. Using this as
      a starting point, 11 significantly regulated reductases and dehydrogenases were
      selected in the present work for further study. The roles of these reductases and
      dehydrogenases in the vanillin tolerance and detoxification abilities of S.
      cerevisiae are described. RESULTS: Among the candidate genes, the overexpression
      of the alcohol dehydrogenase gene ADH6, acetaldehyde dehydrogenase gene ALD6,
      glucose-6-phosphate 1-dehydrogenase gene ZWF1, NADH-dependent aldehyde reductase
      gene YNL134C, and aldo-keto reductase gene YJR096W increased 177, 25, 6, 15, and
      18 % of the strain MUmax in the medium containing 1 g L(-1) vanillin. The in
      vitro detected vanillin reductase activities of strain overexpressing ADH6,
      YNL134C and YJR096W were notably higher than control. The vanillin specific
      reduction rate increased by 8 times in ADH6 overexpressed strain but not in
      YNL134C and YJR096W overexpressed strain. This suggested that the enzymes encoded
      by YNL134C and YJR096W might prefer other substrate and/or could not show their
      effects on vanillin on the high background of Adh6p in vivo. Overexpressing ALD6
      and ZWF1 mainly increased the [NADPH]/[NADP(+)] and [GSH]/[GSSG] ratios but not
      the vanillin reductase activities. Their contribution to strain growth and
      vanillin reduction were balancing the redox state of strain when vanillin was
      presented. CONCLUSIONS: Beside the reported Adh6p, the enzymes encoded by YNL134C
      and YJR096W were proved to have vanillin reduction activity in present study.
      While ALD6 and ZWF1 did not directly reduce vanillin to vanillyl alcohol, their
      contribution to vanillin resistance primarily depended on the enhancement of the
      reducing equivalent supply.

PMID- 27036140
TI  - Impact of health insurance status changes on healthcare utilisation patterns: a
      longitudinal cohort study in South Korea.
AB  - OBJECTIVES: The study examined medical care utilisation by health insurance
      status changes. SETTING: The Korean Welfare Panel Study (KoWePs) was used.
      PARTICIPANTS: This study analysed 14,267 participants at baseline (2006).
      INTERVENTIONS: The individuals were categorised into four health insurance status
      groups: continuous health insurance, change from health insurance to Medical Aid,
      change from Medical Aid to health insurance, or continuous Medical Aid. PRIMARY
      AND SECONDARY OUTCOME MEASURES: Three dependent variables were also analysed:
      days spent in hospital; number of outpatient visits; and hospitalisations per
      year. Longitudinal data analysis was used to determine whether changes in health
      insurance status were associated with healthcare utilisation. RESULTS: The number
      of outpatient visits per year was 0.1.363 times higher (p<0.0001) in the
      continuous Medical Aid than in the continuous health insurance group. The number
      of hospitalisations per year was 1.560 times higher (p<0.001) in new Medical Aid
      and -0.636 times lower (p<0.001) in new health insurance than in continuous
      health insurance group. The number of days spent in hospital per year was -0.567
      times lower (p=0.021) in the new health insurance than in the continuous health
      insurance group. CONCLUSIONS: Health insurance beneficiaries with a coverage
      level lower than Medical Aid showed lower healthcare utilisation, as measured by
      the number of hospitalisations and days spent in hospital per year.

PMID- 27036141
TI  - Towards a standardised informed consent procedure for live donor nephrectomy: the
      PRINCE (Process of Informed Consent Evaluation) project-study protocol for a
      nationwide prospective cohort study.
AB  - INTRODUCTION: Informed consent is mandatory for all (surgical) procedures, but it
      is even more important when it comes to living kidney donors undergoing surgery
      for the benefit of others. Donor education, leading to informed consent, needs to
      be carried out according to certain standards. Informed consent procedures for
      live donor nephrectomy vary per centre, and even per individual healthcare
      professional. The basis for a standardised, uniform surgical informed consent
      procedure for live donor nephrectomy can be created by assessing what information
      donors need to hear to prepare them for the operation and convalescence. METHODS
      AND ANALYSIS: The PRINCE (Process of Informed Consent Evaluation) project is a
      prospective, multicentre cohort study, to be carried out in all eight Dutch
      kidney transplant centres. Donor knowledge of the procedure and postoperative
      course will be evaluated by means of pop quizzes. A baseline cohort (prior to
      receiving any information from a member of the transplant team in one of the
      transplant centres) will be compared with a control group, the members of which
      receive the pop quiz on the day of admission for donor nephrectomy. Donor
      satisfaction will be evaluated for all donors who completed the admission pop
      quiz. The primary end point is donor knowledge. In addition, those elements that
      have to be included in the standardised format informed consent procedure will be
      identified. Secondary end points are donor satisfaction, current informed consent
      practices in the different centres (eg, how many visits, which personnel, what
      kind of information is disclosed, in which format, etc) and correlation of donor
      knowledge with surgeons' estimation thereof. ETHICS AND DISSEMINATION: Approval
      for this study was obtained from the medical ethical committee of the Erasmus MC,
      University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has
      been obtained from the local ethics committees in six participating centres.
      Approval in the last centre has been sought. RESULTS: Outcome will be published
      in a scientific journal. TRIAL REGISTRATION NUMBER: NTR5374; Pre-results.

PMID- 27036142
TI  - Molecular genetic analysis of patients with sporadic and X-linked infantile
      nystagmus.
AB  - OBJECTIVES: Infantile nystagmus (IN) is a genetically heterogeneous condition
      characterised by involuntary rhythmic oscillations of the eyes accompanied by
      different degrees of vision impairment. Two genes have been identified as mainly
      causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic
      basis of both sporadic IN and X-linked IN. DESIGN: Prospective analysis.
      PATIENTS: Twenty Chinese patients, including 15 sporadic IN cases and 5 from X
      linked IN families, were recruited and underwent molecular genetic analysis. We
      first performed PCR-based DNA sequencing of the entire coding region and the
      splice junctions of the FRMD7 and GPR143 genes in participants. Mutational
      analysis and co-segregation confirmation were then performed. SETTING: All
      clinical examinations and genetic experiments were performed in the Eye Hospital
      of Wenzhou Medical University. RESULTS: Two mutations in the FRMD7 gene,
      including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported
      missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X
      linked IN families. However, none of putative mutations were identified in FRMD7
      or GPR143 in any of the sporadic cases. CONCLUSIONS: The results suggest that
      mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not
      of sporadic IN. Our findings provide further insights into FRMD7 mutations, which
      could be helpful for future genetic diagnosis and genetic counselling of Chinese
      patients with nystagmus.

PMID- 27036143
TI  - Solid and liquid media for isolating and cultivating acidophilic and acid
      tolerant sulfate-reducing bacteria.
AB  - Growth media have been developed to facilitate the enrichment and isolation of
      acidophilic and acid-tolerant sulfate-reducing bacteria (aSRB) from environmental
      and industrial samples, and to allow their cultivation in vitro The main features
      of the 'standard' solid and liquid devised media are as follows: (i) use of
      glycerol rather than an aliphatic acid as electron donor; (ii) inclusion of
      stoichiometric concentrations of zinc ions to both buffer pH and to convert
      potentially harmful hydrogen sulphide produced by the aSRB to insoluble zinc
      sulphide; (iii) inclusion of Acidocella aromatica (an heterotrophic acidophile
      that does not metabolize glycerol or yeast extract) in the gel underlayer of
      double layered (overlay) solid media, to remove acetic acid produced by aSRB that
      incompletely oxidize glycerol and also aliphatic acids (mostly pyruvic) released
      by acid hydrolysis of the gelling agent used (agarose). Colonies of aSRB are
      readily distinguished from those of other anaerobes due to their deposition and
      accumulation of metal sulphide precipitates. Data presented illustrate the
      effectiveness of the overlay solid media described for isolating aSRB from acidic
      anaerobic sediments and low pH sulfidogenic bioreactors.

PMID- 27036144
TI  - Keeping it simple: lessons from the golden era of antibiotic discovery.
AB  - Bacteria are becoming increasingly resistant to currently used antibiotics. At
      the same time, little progress has been made in discovering new antibacterial
      drugs to combat resistant organisms. History teaches us that 'high tech' target
      based complex methods are not synonymous with success and a return to simple,
      systematic screening of natural products against bacteria from traditional and
      novel resources holds our greatest hope of success.

PMID- 27036145
TI  - Methanogen communities in a municipal landfill complex in China.
AB  - Landfills are significant global sources of atmospheric methane, but little is
      known about the ecology and community structure of methanogens in these sites.
      Here, we investigated the methanogen community based on methyl coenzyme M
      reductase A gene amplicons in the vertical profiles of three different sites at a
      municipal landfill complex in China. Links between methanogen communities and
      refuse properties were explored using multivariate analysis. Clone library
      results showed that most clones (92%) were related to the hydrogenotrophic
      methanogens, Methanomicrobiales. Almost all of the Methanomicrobiales clones
      retrieved in this study are members of the genus Methanoculleus Eight clones were
      affiliated with the genus Methanofollis The remaining clones were clustered
      within the genus Methanosarcina Terminal restriction fragment length polymorphism
      profiles showed that the landfill was predominated by 22 taxa, making up 69%-96%
      of the community. Of these, a single taxon comprised 36%-65% of the communities
      across all sites and depths. Principal components analysis separated the
      methanogen community into three groups, irrespective of site or depth. Redundancy
      analysis suggested that total phosphorus and pH play roles in structuring
      methanogen communities in landfills.

PMID- 27036146
TI  - Association between ECE1 gene polymorphisms and risk of intracerebral
      haemorrhage.
AB  - OBJECTIVE: To determine whether endothelin converting enzyme-1 (ECE1) gene
      polymorphisms contribute to susceptibility to intracerebral haemorrhage (ICH) by
      influencing blood pressure. METHODS: This case-control study enrolled patients
      with ICH and healthy control subjects from a Southern Han Chinese population. The
      ECE1 gene polymorphisms rs212528 and rs213045 were genotyped. The association
      between the genotypes and the risk of ICH was assessed. The effects of these two
      ECE1 gene polymorphisms on blood pressure were also analysed. RESULTS: A total of
      389 patients with ICH and 404 healthy control subjects participated in the study.
      There was no significant association between the ECE1 rs212528 and rs213045
      polymorphisms and ICH even after adjusting for different confounding variables.
      In patients with ICH, the systolic blood pressure of patients with the rs212528
      AA genotype was significantly lower than that of patients with the AG/GG
      genotypes. CONCLUSIONS: These results indicated that the ECE1 rs212528 and
      rs213045 polymorphisms had no major role to play in the genetic susceptibility to
      ICH, although rs212528 might influence blood pressure in patients with ICH.

PMID- 27036147
TI  - A 5-year analysis of semen parameters in Saudi Arabian men attending infertility
      clinics.
AB  - OBJECTIVE: To evaluate semen parameters in infertile Saudi Arabian men. METHODS:
      In this retrospective study, semen analysis and other clinical data were
      extracted from medical records of men attending an infertility clinic. Patients
      were stratified according to smoking status and presence or absence of
      varicocele. RESULTS: The study included 425 patients. Nonsmokers (n = 322) had
      significantly higher serum testosterone and sperm motility than smokers (n =
      194). Serum testosterone, semen volume, motility, morphology, sperm/ejaculation
      and sperm count were significantly higher in patients without varicocele (n =
      328) than in those with varicocele (n = 188). CONCLUSIONS: In this study, smoking
      and the presence of varicocele had negative effects on semen parameters in
      infertile men.

PMID- 27036148
TI  - Study of the relationship between male erectile dysfunction and type 2 diabetes
      mellitus/metabolic syndrome and its components.
AB  - AIM: To study the relationship between erectile dysfunction and type 2 diabetes
      mellitus (T2DM)/metabolic syndrome (MetS). METHODS: This prospective study
      invited male patients with T2DM attending for a routine outpatient check-up to
      complete two questionnaires. A general questionnaire was used to collect
      demographic and clinical characteristics, while sexual function was assessed
      using the International Index of Erectile Function scoring system. The prevalence
      of MetS in this patient population was determined using information from the
      general questionnaire. Risk factors for erectile dysfunction were identified
      using univariate and multivariate logistic regression analyses. RESULTS: A total
      of 175 patients provided valid questionnaires; of these, 148 (84.6%) had MetS.
      The prevalence of erectile dysfunction was 90.9% (159/175) in the entire survey
      population compared with 89.2% (132/148) in patients with MetS. Multivariate
      logistic regression analysis identified the following risk factors for erectile
      dysfunction in patients with T2DM and/or MetS: age, blood pressure and duration
      of diabetes. CONCLUSION: These current findings suggest that the MetS and its
      components have a negative impact on male erectile function.

PMID- 27036149
TI  - Systematic review: effect of psychiatric symptoms on return to work after
      occupational injury.
AB  - BACKGROUND: Although post-traumatic stress disorder (PTSD) and depression are
      commonly observed following injury, few studies have focused on the effect of
      psychiatric symptoms on return to work (RTW) following occupational injury. AIMS:
      To determine the impact of psychiatric symptoms on RTW after occupational injury.
      METHODS: PubMed (1980-2014), MEDLINE (1980-2014) and PsycINFO (1980-2014)
      databases were examined with linked fields of research in February 2015.
      Reference lists of eligible articles were also searched. Cohort, case-control,
      cross-sectional studies and intervention studies were selected according to
      predefined criteria. Evidence was synthesized qualitatively according to the
      Downs and Black and Crombie checklist. The standard checklist was used to assess
      the methodological quality of each study by two reviewers. RESULTS: Five of the
      56 records met the inclusion and exclusion criteria. After occupational injury,
      the rates of RTW after the injuries varied widely, ranging from 31 to 63%. PTSD
      symptoms and depressive symptoms appeared to be negatively associated with RTW.
      CONCLUSIONS: Currently, the evidence is insufficient to draw conclusions about
      the effects of psychiatric symptoms on RTW after occupational injury and more
      studies are needed. Future studies with large sample sizes are warranted to
      determine the prevalence of RTW and to detect the psychiatric factors.

PMID- 27036150
TI  - Anaphylactic reaction in a hairdresser due to sensitization to persulphates.
AB  - Severe occupational systemic reactions to persulphates have rarely been described
      and if so mainly after skin contact with bleaching products. We report the first
      case of a hairdresser with an allergy to persulphates obtained during
      professional work, who developed anaphylaxis caused by persulphates present in
      dental cement during dental treatment. This case documents that sensitization to
      occupational allergens can induce severe systemic reactions outside the
      workplace. Additionally, it also recommends the need for greater awareness of
      medical professionals, including dentists, of the possibility of anaphylaxis in
      patients with occupational allergy. 

PMID- 27036151
TI  - The occupational risk of tuberculosis in a low-prevalence population.
AB  - BACKGROUND: The incidence of tuberculosis (TB) infection in low-prevalence
      countries has been declining. Estimates of the risk of occupational TB in these
      countries are contradictory. AIMS: To evaluate the risk of occupational TB in a
      low-prevalence population using a comprehensive database. METHODS: All
      compensation claims in British Columbia (BC), Canada, reporting workplace TB
      exposure for the years 1999-2008 were reviewed. Cases with TB infection were
      identified for all occupational groups with five or more claims in the decade and
      analysis provided estimates of incidence rates of active TB and relative risks of
      latent TB (LTB) infections. RESULTS: There were 70 occupational groups making 639
      claims including 100 with LTB and eight with active TB. Only 18 occupations had
      five or more claims. Four occupational groups had a significantly increased
      relative risk of infection compared with all other occupational groups. These
      were employment counsellors, registered nurses, x-ray technicians and home
      support workers. Active TB infections were relatively rare compared with the
      general population (1-4 compared with 7-10/100000 person-years, respectively).
      CONCLUSIONS: Few occupational groups were at risk of TB exposure at work on a
      regular basis. Only a handful had an apparent increased risk of contracting TB
      and these should be the focus of prevention efforts. Work-related active TB
      infections are rare hence the burden of occupational TB disease is low in BC.

PMID- 27036152
TI  - Adult Attachment Styles, Destructive Conflict Resolution, and the Experience of
      Intimate Partner Violence.
AB  - Although there is ample evidence linking insecure attachment styles and intimate
      partner violence (IPV), little is known about the psychological processes
      underlying this association, especially from the victim's perspective. The
      present study examined how attachment styles relate to the experience of sexual
      and psychological abuse, directly or indirectly through destructive conflict
      resolution strategies, both self-reported and attributed to their opposite-sex
      romantic partner. In an online survey, 216 Spanish undergraduates completed
      measures of adult attachment style, engagement and withdrawal conflict resolution
      styles shown by self and partner, and victimization by an intimate partner in the
      form of sexual coercion and psychological abuse. As predicted, anxious and
      avoidant attachment styles were directly related to both forms of victimization.
      Also, an indirect path from anxious attachment to IPV victimization was detected
      via destructive conflict resolution strategies. Specifically, anxiously attached
      participants reported a higher use of conflict engagement by themselves and by
      their partners. In addition, engagement reported by the self and perceived in the
      partner was linked to an increased probability of experiencing sexual coercion
      and psychological abuse. Avoidant attachment was linked to higher withdrawal in
      conflict situations, but the paths from withdrawal to perceived partner
      engagement, sexual coercion, and psychological abuse were non-significant. No
      gender differences in the associations were found. The discussion highlights the
      role of anxious attachment in understanding escalating patterns of destructive
      conflict resolution strategies, which may increase the vulnerability to IPV
      victimization.

PMID- 27036153
TI  - Lesbian, Gay, and Bisexual Adults: Childhood Gender Nonconformity, Childhood
      Trauma, and Sexual Victimization.
AB  - The present study examined whether the relationship between childhood gender
      nonconformity and sexual victimization in adulthood among lesbian, gay, and
      bisexual (LGB) same-sex attracted men and women is mediated by experiences with
      childhood trauma experiences by an adult family member. Data are based on a
      survey among same-sex attracted individuals (N= 2,352; 1,396 men and 956
      women;Mage= 44.97) recruited from an online research panel. Participants
      completed an online questionnaire consisting of existing scales. Sixteen percent
      of the participants reported that they had experienced sexual victimization as an
      adult. There were gender differences: Men reported less childhood gender
      nonconformity and women more often reported experiences with childhood trauma by
      an adult family member and sexual victimization as an adult. Bootstrapped
      mediation analysis and follow-up moderated mediation analyses showed that
      childhood trauma significantly mediated the relation between childhood gender
      nonconformity and experiences of sexual victimization for men but not for women.
      In other words, for men higher levels of childhood gender nonconformity predicted
      experiences with childhood trauma by an adult family member, which in turn
      predicted the higher prevalence of sexual victimization. Implementations of these
      findings are that interventions aimed at increasing the social acceptance of
      gender nonconformity might also lower the levels of childhood trauma and sexual
      victimization among gay and bisexual men. Professionals working with children
      (and especially with boys) should be aware of the impact of gender nonconformity
      on childhood trauma and experiences of sexual victimization later in life.

PMID- 27036154
TI  - Child Abuse as a Predictor of Alcohol Consumption Among Brazilian University
      Students.
AB  - Alcohol use among university students has received considerate attention in
      recent years due to its serious consequences. There is insufficient data in terms
      of the relationship between child abuse history and future use of alcohol in such
      a group. In addition, little is known about the effects of polyvictimization
      (lifetime multiple victimization experiences) on the consumption of these young
      adults. This study has examined whether a history of exposure to intimate partner
      violence (IPV) and/or child abuse is related to alcohol consumption. Particular
      attention was given to different forms of victimization (physical, psychological,
      sexual abuse, and exposure to IPV) occurring over the life of the individual. A
      questionnaire that underwent a process of adaptation in two pilot studies,
      incorporating the Alcohol Use Disorders Identification Test (AUDIT) and questions
      about child abuse history, was used. The questionnaire was applied to 1,452
      students in Brazil. Child abuse and polyvictimization were related to higher
      alcohol intake and binge consumption in the last 3 months. Physical,
      psychological, and exposure to IPV were polyvictimization forms with the most
      impact on alcohol consumption. The study points out the need to initiate
      prevention strategies among Brazilian university students for a decrease of
      harmful alcohol consumption, as well as prevention of family violence.

PMID- 27036155
TI  - The Geography of Child Maltreatment: A Spatiotemporal Analysis Using Bayesian
      Hierarchical Analysis With Integrated Nested Laplace Approximation.
AB  - This study quantifies the spatiotemporal risk of child abuse and neglect in Los
      Angeles at the census tract level over a recent 4-year period, identifies areas
      of increased risk, and evaluates the role of structural disadvantage in
      substantiated child maltreatment referrals. Child maltreatment data on 83,379
      child maltreatment cases in 1,678 census tracts spanning 2006-2009 were obtained
      from the Los Angeles County Department of Children and Family Services.
      Substantiated referral counts were analyzed across census tracts with Bayesian
      hierarchical spatial models using integrated nested Laplace approximations.
      Results showed that the unadjusted yearly rate of child abuse and neglect held
      fairly steady over the study period decreasing by only 2.57%. However, the
      temporal term in the spatiotemporal model reflected a downward trend beginning in
      2007. High rates of abuse and neglect were predicted by several neighborhood
      level measures of structural burden. Every 1-unit decrease in the social
      vulnerability index reduced the risk of child abuse and neglect by 98.3% (95% CrI
      = 1.869-2.1042) while every 1-unit increase in the Black-White dissimilarity
      index decreased child abuse and neglect risk by 70.6%. The interaction of these
      variables demonstrated the protective effect of racial heterogeneity in socially
      vulnerable neighborhoods. No such effect was found in neighborhoods characterized
      by low levels of vulnerability. Population-based child abuse and neglect
      prevention and intervention efforts should be aided by the characteristics of
      neighborhoods that demonstrate strong spatial patterns even after accounting for
      the role of race and place.

PMID- 27036156
TI  - Providing and Receiving Sexual Assault Disclosures: Findings From a Sexually
      Diverse Sample of Young Adults.
AB  - This study utilized a sample of primarily lesbian, gay, bisexual, and queer
      (LGBQ)-identified young adults from across the United States to pilot test a new
      instrument, the Reactions Provided to Disclosures Questionnaire (RPDQ), and
      assess the disclosure experience for both those who provide and those who receive
      disclosures of sexual assault. Results indicate that the experience of sexual
      assault disclosure in the LGBQ community is similar to the heterosexual community
      in that most victims disclose their assaults, most often to a friend, and were
      most likely to receive the reaction Emotional Support. Victims were also likely
      to receive the reaction Victim Blaming, especially if they disclosed to formal
      sources, such as law enforcement, medical, or religious personnel. This study
      also examined the relationship between the types of assault experienced and
      disclosure reactions received. Experiencing an anal assault was significantly
      associated with Victim Blaming reactions. A central aim of this study was to
      examine how respondents who received (rather than provided) a disclosure reacted,
      a question not been adequately addressed in prior literature. The RPDQ (a
      modification of Ullman's Social Reactions Questionnaire), which was piloted here,
      factored in to five types of reactions: Emotional Support, Affectionate Support,
      Empathetic Support, Tangible Aid and Information Support, and Egocentric
      Reactions. Sexual assault survivors were more likely to report that they provided
      Emotional Support and Affectionate Support after receiving a disclosure than were
      nonsurvivors.

PMID- 27036157
TI  - Longitudinal Changes in Self-Efficacy, Mental Health, Abuse, and Stages of
      Change, for Women Fearful of a Partner: Findings From a Primary Care Trial
      (WEAVE).
AB  - Women seeking healthcare while experiencing intimate partner violence (IPV) often
      report a mismatch between healthcare received and desired. An increase in
      detection of women experiencing IPV through routine screening has not
      consistently shown a parallel increase in uptake of referrals or decreased abuse.
      This study investigates relationships between women's stage of change (SOC),
      mental health, abuse, social support, and self-efficacy. This study used data
      from a randomized-controlled trial (RCT) of an intervention to improve outcomes
      for women afraid of their partners ( n = 225; WEAVE). Women's progress toward
      change was categorized into pre-contemplation/contemplation (pre-change SOC) or
      preparation/action/maintenance of change (change-related SOC). Characteristics of
      women ending the 2-year study in pre-change SOC were compared with those always
      in change-related and those ending in change-related SOC. Variables were analyzed
      using multinomial logistic regressions at baseline, 6, 12, and 24 months.
      Compared with women in pre-change SOC, women always in change-related SOC or
      ending in change-related SOC are significantly more likely to have higher levels
      of self-efficacy at 6 (AdjOR = 1.19, confidence interval [CI] = [1.08, 1.30]) and
      24 months (AdjOR = 1.21, CI = [1.04, 1.40]). Women always in change-related SOC
      are always significantly less likely to live with an intimate partner. Women
      ending in change-related SOC are less likely to live with a partner at 12 (AdjOR
      = 0.30, CI = [0.12, 0.75]) and 24 (AdjOR = 0.22, CI = [0.06, 0.80]) months.
      Clinicians should focus on enhancing abused women's self-efficacy, supporting
      them to create and maintain positive changes.

PMID- 27036158
TI  - Tumor suppressors BTG1 and BTG2 regulate early mouse B-cell development.

PMID- 27036159
TI  - Improved graft-versus-host disease-free, relapse-free survival associated with
      bone marrow as the stem cell source in adults.
AB  - We previously reported that bone marrow grafts from matched sibling donors
      resulted in best graft-versus-host disease-free, relapse-free survival at 1-year
      post allogeneic hematopoietic cell transplantation. However, pediatric patients
      comprised the majority of bone marrow graft recipients in that study. To better
      define this outcome in adults and pediatric patients at 1- and 2-years post-
      allogeneic hematopoietic cell transplantation, we pooled data from the University
      of Minnesota and the Hopital Saint-Louis in Paris, France (n=1901). Graft-versus
      host disease-free, relapse-free survival was defined as the absence of grade III
      IV acute graft-versus-host disease, chronic graft-versus-host disease (requiring
      systemic therapy or extensive stage), relapse and death. In adults, bone marrow
      from matched sibling donors (n=123) had best graft-versus-host disease-free,
      relapse-free survival at 1- and 2-years, compared with peripheral blood stem cell
      from matched sibling donors (n=540) or other graft/donor types. In multivariate
      analysis, peripheral blood stem cells from matched sibling donors resulted in a
      50% increased risk of events contributing to graft-versus-host disease-free,
      relapse-free survival at 1- and 2-years than bone marrow from matched sibling
      donors. With limited numbers of peripheral blood stem cell grafts in pediatric
      patients (n=12), graft-versus-host disease-free, relapse-free survival did not
      differ between bone marrow and peripheral blood stem cell graft from any donor.
      While not all patients have a matched sibling donor, graft-versus-host disease
      free, relapse-free survival may be improved by the preferential use of bone
      marrow for adults with malignant diseases. Alternatively, novel graft-versus-host
      disease prophylaxis regimens are needed to substantially impact graft-versus-host
      disease-free, relapse-free survival with the use of peripheral blood stem cell.

PMID- 27036160
TI  - Salvage therapy with high-dose cytarabine and mitoxantrone in combination with
      all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia
      refractory to first induction therapy.
AB  - Outcome of patients with primary refractory acute myeloid leukemia remains
      unsatisfactory. We conducted a prospective phase II clinical trial with
      gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid
      (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose
      cytarabine (3 g/m(2)/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m(2)
      intravenously on days 2-3) in 93 patients aged 18-60 years refractory to one
      cycle of induction therapy. Primary end point of the study was response to
      therapy; secondary end points included evaluation of toxicities, in particular,
      rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell
      transplantation. Complete remission or complete remission with incomplete blood
      count recovery was achieved in 47 (51%) and partial remission in 10 (11%)
      patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had
      refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell
      transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients
      developed moderate or severe sinusoidal obstruction syndrome after
      transplantation. Four-year overall survival rate was 32% (95% confidence interval
      24%-43%). Patients responding to salvage therapy and undergoing allogeneic
      hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95%
      confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal
      tandem duplication positive acute myeloid leukemia had a poor outcome despite
      transplantation. In conclusion, the described regimen is an effective and
      tolerable salvage therapy for patients who are primary refractory to one cycle of
      conventional intensive induction therapy. (clinicaltrials.gov identifier:
      00143975).

PMID- 27036161
TI  - A novel mechanism of NPM1 cytoplasmic localization in acute myeloid leukemia: the
      recurrent gene fusion NPM1-HAUS1.

PMID- 27036162
TI  - The association of aberrant folylpolyglutamate synthetase splicing with ex vivo
      methotrexate resistance and clinical outcome in childhood acute lymphoblastic
      leukemia.

PMID- 27036163
TI  - Multimodal intervention integrated into the clinical management of acute leukemia
      improves physical function and quality of life during consolidation chemotherapy:
      a randomized trial 'PACE-AL'.

PMID- 27036164
TI  - Image-Derived Assessment of Left Ventricular Mass in Fetal Myocardial Hypertrophy
      by 4-Dimensional Echocardiography: An In Vitro Study.
AB  - OBJECTIVES: This study tested the accuracy of new 4-dimensional fetal
      echocardiography to evaluate left ventricular (LV) mass in an experimental model
      of fetal myocardial hypertrophy. METHODS: Ten fresh rabbit hearts were studied.
      Fetal myocardial hypertrophy was simulated by fixing different amounts of
      myocardial tissue to the LV epicardium. A small latex balloon was mounted on
      vinyl tubing and fixed within each LV cavity. The proximal end of the tube was
      attached to a pulsatile pump apparatus. The pump was calibrated to deliver stroke
      volumes of 2 and 4 mL at stroke rates of 60 and 120 beats per minute (bpm). Four
      dimensional data were acquired and analyzed with quantification software.
      Reference values for LV mass were determined by the displacement method. RESULTS:
      Echo-derived measurements of LV mass showed good correlations with reference
      values at all stroke rates and stroke volumes: at 2 mL and 60 bpm, r = 0.95; at 2
      mL and 120 bpm, r = 0.95; at 4 mL and 60 bpm, r = 0.93; and at 4 mL and 120 bpm,
      r = 0.95 (P< .01 for all values). There was also excellent interobserver (r =
      0.98; mean difference of -0.32 g; -4.4% of the mean) and intraobserver (r = 0.98;
      mean difference of -0.28 g; -3.8% of the mean) agreement. CONCLUSIONS: In this
      controlled in vitro study, high-resolution 4-dimensional echocardiography was
      shown to accurately assess LV mass and have the potential to evaluate fetal
      myocardial hypertrophy.

PMID- 27036165
TI  - Assessment of Left Ventricular Dissipative Energy Loss by Vector Flow Mapping in
      Patients With End-Stage Renal Disease.
AB  - OBJECTIVES: Dissipative energy loss derived from vector flow mapping represents
      the viscous dissipation of turbulent blood flow. We aimed to determine the left
      ventricular (LV) energy loss in patients with end-stage renal disease (ESRD).
      METHODS: Patients with ESRD and a preserved LV ejection fraction, who consisted
      of a group receiving peritoneal dialysis, a group receiving hemodialysis, and a
      group receiving preparation for dialysis initiation, were examined by
      echocardiography; a group of healthy control participants were examined as well.
      Vector flow mapping analysis was then performed from the apical 4-chamber view to
      calculate the energy loss during diastole and systole in the left ventricle.
      RESULTS: Conventional transthoracic echocardiography and LV energy loss
      calculations were successfully performed in 63 cases and 50 controls. The
      patients with ESRD had significantly higher diastolic energy loss [median
      (interquartile range), 71.73 (46.08-106.75) versus 23.32 (17.17-29.26) mW/m; P <
      .001] and higher systolic energy loss [25.28 (19.03-33.93) versus 12.52 (9.35
      16.47) mW/m; P < .001]. A significant difference in diastolic energy loss between
      the peritoneal dialysis and preparation groups was found [54.92 (39.28-89.94)
      versus 84.82 (62.58-171.4) mW/m; P = .04]. In patients with ESRD, the log
      transformed diastolic energy loss had a significant association with the peak
      early diastolic transmitral flow velocity (P = .011), peak early diastolic
      transmitral flow velocity-to-peak early diastolic mitral annular flow velocity
      ratio (P = .001), LV mass index (P = .017), and heart rate (P = .003).
      CONCLUSIONS: Impaired blood flow efficiency was detected in patients with ESRD by
      using dissipative energy loss derived from vector flow mapping. The energy loss
      value could be a novel parameter for evaluating the ventricular workload of
      uremic hearts in terms of fluid mechanics.

PMID- 27036166
TI  - Normal Sonographic Anatomy of the Wrist With Emphasis on Assessment of Tendons,
      Nerves, and Ligaments.
AB  - Sonography allows for rapid, cost-effective, noninvasive, and dynamic evaluation
      of soft tissue structures, thus representing a valuable tool for ruling out
      musculoskeletal disorders of the wrist. Because of the complexity of the wrist
      joint, sonographic training and familiarity with normal and variant anatomy are
      needed to avoid misdiagnosis and improper treatment. The aim of this article is
      to enlighten readers about the structures representing normal findings or common
      variants during sonographic evaluations of the wrist. The main text reviews the
      pertinent gross anatomy and procedures that are recommended to assess the soft
      tissue structures of the wrist, with particular emphasis given to tendons,
      nerves, and ligaments. Detailed explanations of the scanning techniques and
      sonographic appearance of the wrist structures are provided in the figure
      legends. 

PMID- 27036167
TI  - Ultrasound-Guided Transcutaneous Needle Biopsy of the Base of the Tongue and
      Floor of the Mouth From a Submental Approach.
AB  - Limited data exist regarding the feasibility of ultrasound-guided transcutaneous
      biopsy of the base of the tongue and floor of the mouth. This retrospective study
      reviewed 8 cases with lesions in the base of the tongue or floor of the mouth
      that were biopsied by fine-needle aspiration. Core biopsy was also needed in 1
      case. All biopsies were technically successful, and all yielded squamous cell
      carcinoma. One biopsy yielded a false-positive result, as subsequent resection
      yielded high-grade dysplasia with no invasion. The other biopsy results were
      considered true-positive based on subsequent pathologic examinations (2 cases) or
      clinical/imaging follow-up (5 cases). There were no significant complications
      associated with the biopsies. 

PMID- 27036168
TI  - Shear Wave Elastography of the Spleen for Monitoring Transjugular Intrahepatic
      Portosystemic Shunt Function: A Pilot Study.
AB  - OBJECTIVES: To assess the feasibility of splenic shear wave elastography in
      monitoring transjugular intrahepatic portosystemic shunt (TIPS) function.
      METHODS: We measured splenic shear wave velocity (SWV), main portal vein velocity
      (PVV), and splenic vein velocity (SVV) in 33 patients 1 day before and 3 days to
      12 months after TIPS placement. We also measured PVV, SVV, and SWV in 10 of 33
      patients with TIPS dysfunction 1 day before and 3 to 6 days after TIPS revision.
      Analyses included differences in portosystemic pressure gradient (PPG), PVV, SVV,
      and mean SWV before and after TIPS procedures; comparison of median SWV before
      and after TIPS procedures; differences in PVV, SVV, and SWV before and at
      different times up to 12 months after TIPS placement; accuracy of PVV, SVV, and
      SWV in determining TIPS dysfunction; and correlation between PPG and SWV.
      RESULTS: During 12 months of follow-up, 23 of 33 patients had functioning TIPS,
      and 10 had TIPS dysfunction. The median SWV was significantly different before
      and after primary TIPS placement (3.60 versus 3.05 m/s; P = .005), as well as
      before and after revision (3.73 versus 3.06 m/s; P = .003). The PPG, PVV, and SVV
      were also significantly different before and after TIPS placement and revision (P
      < .001). The PPG and SWV decreased, whereas PVV and SVV increased, after
      successful TIPS procedures. A positive correlation was observed between PPG and
      SWV (r = 0.70; P < .001), and a negative correlation was observed between PPG and
      PVV and SVV (r = -0.65; P < .001). The areas under the receiver operating
      characteristic curve for PVV, SVV, and SWV in determining TIPS dysfunction were
      0.82, 0.84, and 0.81, respectively. CONCLUSIONS: Splenic SWV is compatible with
      splenoportal venous velocity in quantitatively monitoring TIPS function and
      determining TIPS dysfunction.

PMID- 27036169
TI  - Dynamic Contrast-Enhanced Sonography and Dynamic Contrast-Enhanced Magnetic
      Resonance Imaging for Preoperative Diagnosis of Infected Nonunions.
AB  - OBJECTIVES: Bone regeneration depends on perfusion of the fracture tissue,
      whereby hypervascularity is associated with infection, which itself causes
      nonunions. To date, nonunion perfusion has not been assessed with contrast
      enhanced sonography. The aim of this study was to evaluate the potential of
      contrast-enhanced sonography in the analysis of nonunion tissue perfusion.
      METHODS: Nonunion vascularity of 31 patients before revision surgery was
      prospectively examined with qualitative contrast-enhanced sonography and dynamic
      contrast-enhanced magnetic resonance imaging (MRI). Time-intensity curves from 2
      minute contrast-enhanced sonographic video clips were generated, and parameters
      such as wash-in rate, rise time, and peak enhancement were quantified. On dynamic
      contrast-enhanced MRI, the initial area under the enhancement curve was
      quantified. Preoperative radiographs, computed tomograms, the clinical nonunion
      score, laboratory infection features, as well as contrast-enhanced sonographic
      and dynamic contrast-enhanced MRI perfusion were correlated with microbiological
      results from the nonunion tissue. RESULTS: Both qualitative and quantitative
      contrast-enhanced sonography showed significant differences between infected and
      aseptic nonunions (P = .015 and .020). The qualitative dynamic contrast-enhanced
      MRI analysis was not significant (P= .244), but after quantification, a strong
      correlation (P = .007) with microbiological results was noted. A receiver
      operating characteristic analysis calculated ideal cutoff values for quantitative
      contrast-enhanced sonography and dynamic contrast-enhanced MRI so that their
      combination detected infected nonunions with sensitivity and specificity of 88.9%
      and 77.3%, respectively. Clinical, radiologic, and laboratory examinations did
      not correlate with microbiological results (P > .05). CONCLUSIONS: Contrast
      enhanced sonography can visualize the vascularity of nonunions in real time,
      while quantification software allows for a semiobjective evaluation of bone
      perfusion. The correlations of both quantitative contrast-enhanced sonography and
      dynamic contrast-enhanced MRI with microbiological results show their high value
      for differentiation of infected from aseptic nonunions.

PMID- 27036170
TI  - Changes in Default Alarm Settings and Standard In-Service are Insufficient to
      Improve Alarm Fatigue in an Intensive Care Unit: A Pilot Project.
AB  - BACKGROUND: Clinical alarm systems safety is a national concern, specifically in
      intensive care units (ICUs) where alarm rates are known to be the highest.
      Interventional projects that examined the effect of changing default alarm
      settings on overall alarm rate and on clinicians' attitudes and practices toward
      clinical alarms and alarm fatigue are scarce. OBJECTIVE: To examine if (1) a
      change in default alarm settings of the cardiac monitors and (2) in-service
      nursing education on cardiac monitor use in an ICU would result in reducing alarm
      rate and in improving nurses' attitudes and practices toward clinical alarms.
      METHODS: This quality improvement project took place in a 20-bed
      transplant/cardiac ICU with a total of 39 nurses. We implemented a unit-wide
      change of default alarm settings involving 17 parameters of the cardiac monitors.
      All nurses received an in-service education on monitor use. Alarm data were
      collected from the audit log of the cardiac monitors 10 weeks before and 10 weeks
      after the change in monitors' parameters. Nurses' attitudes and practices toward
      clinical alarms were measured using the Healthcare Technology Foundation National
      Clinical Alarms Survey, pre- and postintervention. RESULTS: Alarm rate was 87.86
      alarms/patient day (a total of 64,500 alarms) at the preintervention period
      compared to 59.18 alarms/patient day (49,319 alarms) postintervention (P=.01). At
      baseline, Arterial Blood Pressure (ABP), Pair Premature Ventricular Contractions
      (PVCs), and Peripheral Capillary Oxygen Saturation (SpO2) alarms were the
      highest. ABP and SpO2 alarms remained among the top three at the postproject
      period. Out of the 39 ICU nurses, 24 (62%) provided complete pre- and postproject
      survey questionnaires. Compared to the preintervention survey, no remarkable
      changes in the postproject period were reported in nurses' attitudes. Themes in
      the narrative data were related to poor usability of cardiac monitors and the
      frequent alarms. The data showed great variation among nurses in terms of
      changing alarm parameters and frequency of replacing patients' electrodes.
      Despite the in-service, 50% (12/24) of the nurses specified their need for more
      training on cardiac monitors in the postproject period. CONCLUSIONS: Changing
      default alarm settings and standard in-service education on cardiac monitor use
      are insufficient to improve alarm systems safety. Alarm management in ICUs is
      very complex, involving alarm management practices by clinicians, availability of
      unit policies and procedures, unit layout, complexity and usability of monitoring
      devices, and adequacy of training on system use. The complexity of the newer
      monitoring systems requires urgent usability testing and multidimensional
      interventions to improve alarm systems safety and to attain the Joint Commission
      National Patient Safety Goal on alarm systems safety in critical care units.

PMID- 27036175
TI  - Structural development and dorsoventral maturation of the medial entorhinal
      cortex.
AB  - We investigated the structural development of superficial-layers of medial
      entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic
      innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth
      while reelin-positive stellate-cells were scattered throughout development. Layer
      3 and parasubiculum neurons had a transient calbindin-expression, which declined
      with age. Early postnatally, layer-2 pyramidal but not stellate-cells co
      localized with doublecortin - a marker of immature neurons - suggesting delayed
      functional-maturation of pyramidal-cells. Three observations indicated a dorsal
      to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin
      expression in layer-3 neurons decreased progressively from dorsal-to-ventral,
      (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally
      before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than
      ventral parasubiculum. The early appearance of calbindin-pyramidal-grid
      organization in layer-2 suggests that this pattern is instructed by genetic
      information rather than experience. Superficial-layer-microcircuits mature
      earlier in dorsal entorhinal cortex, where small spatial-scales are represented.
      Maturation of ventral-entorhinal-microcircuits - representing larger spatial
      scales - follows later around the onset of exploratory behavior. 

PMID- 27036176
TI  - Protective effect of vaccination against mumps complications, Czech Republic,
      2007-2012.
AB  - BACKGROUND: In the Czech Republic, two-dose immunization against mumps achieves
      98% coverage. The routine reporting detects mumps cases, clinical complications,
      and hospital admissions in unvaccinated but also in vaccinated individuals. Using
      surveillance data of patients with mumps we assessed the effectiveness of mumps
      vaccination on mumps clinical complications and hospitalization need. We also
      investigated the effect of the time since immunization. METHODS: We analysed data
      on incident mumps cases reported to the Czech national surveillance system in
      2007-2012. Using a logistic regression model with adjustment for age, sex, year
      of onset, and the administrative region, the association between vaccination and
      the most frequent mumps complications and hospitalization was evaluated. The
      adjusted odds ratios (ORa) for mumps complications were compared between the
      vaccinated and non-vaccinated groups, reflecting the vaccine effectiveness (VEa)
      computed as VEa = (1-ORa) * 100. We estimated the risk of mumps complications by
      the time from vaccination. RESULTS: From total of 9663 mumps analysed cases 5600
      (58%) occurred in males. The mean age at the disease onset was 17.3, median 16
      years. Ninety percent of the study patients had no complications, while 1.6%
      developed meningitis, 0.2% encephalitis, and 0.6% pancreatitis. Mumps orchitis
      occurred in 659 (11.8%) male cases. In total, 1192 (12.3%) patients required
      hospitalization. Two doses of vaccine received by 81.8% cases significantly
      reduced the risk of hospitalization: ORa 0.29 (95% CI: 0.24, 0.35). Two doses
      showed statistically significant VEa 64% (95% CI: 46, 79) for meningitis, 93%
      (95% CI: 66, 98) for encephalitis in all cases, and 72% (95% CI: 64, 78) for
      orchitis in males. Vaccine effectiveness for orchitis declined from 81 to 74% and
      56% in the most affected age groups 10-14, 15-19, and 20-24 years, respectively.
      Among 7850 two-dose recipients, the rate of complications rose from below 1 to
      16% in categories up to 6 years and 24 and more years after the second dose,
      respectively. CONCLUSIONS: This study demonstrates a significant preventive
      effect of two-dose vaccination against mumps complications (orchitis, meningitis,
      or encephalitis) and hospitalization for mumps. The risk of complications
      increases with time interval from vaccination. Teenagers and young adults were
      the most affected age groups.

PMID- 27036178
TI  - Editorial: Chaos--From simple models to real-world problems.

PMID- 27036177
TI  - Patient-physician discussions about costs: definitions and impact on cost
      conversation incidence estimates.
AB  - BACKGROUND: Nearly one in three Americans are financially burdened by their
      medical expenses. To mitigate financial distress, experts recommend routine
      physician-patient cost conversations. However, the content and incidence of these
      conversations are unclear, and rigorous definitions are lacking. We sought to
      develop a novel set of cost conversation definitions, and determine the impact of
      definitional variation on cost conversation incidence in three clinical settings.
      METHODS: Retrospective, mixed-methods analysis of transcribed dialogue from 1,755
      outpatient encounters for routine clinical management of breast cancer,
      rheumatoid arthritis, and depression, occurring between 2010-2014. We developed
      cost conversation definitions using summative content analysis. Transcripts were
      evaluated independently by at least two members of our multi-disciplinary team to
      determine cost conversation incidence using each definition. Incidence estimates
      were compared using Pearson's Chi-Square Tests. RESULTS: Three cost conversation
      definitions emerged from our analysis: (a) Out-of-Pocket (OoP) Cost--discussion
      of the patient's OoP costs for a healthcare service; (b) Cost/Coverage-
      discussion of the patient's OoP costs or insurance coverage; (c) Cost of Illness-
      discussion of financial costs or insurance coverage related to health or
      healthcare. These definitions were hierarchical; OoP Cost was a subset of
      Cost/Coverage, which was a subset of Cost of Illness. In each clinical setting,
      we observed significant variation in the incidence of cost conversations when
      using different definitions; breast oncology: 16, 22, 24% of clinic visits
      contained cost conversation (OOP Cost, Cost/Coverage, Cost of Illness,
      respectively; P < 0.001); depression: 30, 38, 43%, (P < 0.001); and rheumatoid
      arthritis, 26, 33, 35%, (P < 0.001). CONCLUSIONS: The estimated incidence of
      physician-patient cost conversation varied significantly depending on the
      definition used. Our findings and proposed definitions may assist in
      retrospective interpretation and prospective design of investigations on this
      topic.

PMID- 27036179
TI  - Expectation formation in an overlapping generation model with production.
AB  - In this paper, we investigate the dynamic properties of an overlapping
      generations' model with capital accumulation, in which agents work in both
      periods of life. We compare three different expectation mechanisms: perfect
      foresight, myopic foresight, and adaptive expectations, focusing, in particular,
      on this last one. We show that the steady state is the same under each mechanism,
      and we prove its global stability for perfectly foresighted agents. After
      investigating local stability conditions under myopic expectations, we study in
      detail the case of adaptive expectations. We show that, under both reduced
      rationality mechanisms, if the share of time devoted to labor in the second
      period of life is large enough, periodic and complex dynamics can occur.
      Moreover, deepening the investigation through numerical simulations, we study the
      global stability behavior under adaptive expectations. Such complex scenarios
      also include the coexistence between the stable steady state and a periodic or
      chaotic attractor, giving rise to multistability, which does not arise under
      myopic expectations. Finally, we provide some considerations about the
      possibility for the agents to improve their forecasts by observing the
      forecasting error time series. 

PMID- 27036180
TI  - Algorithms for concatenating templates.
AB  - We present two algorithms for concatenating two branched manifolds. There exist
      two common ways to describe representations of branched manifolds with linking
      matrices. The algorithms provided permit to concatenate branched manifolds with
      each representation: a linking matrix with an array or only one linking matrix.
      We also provide algorithms to switch between these two descriptions. 

PMID- 27036181
TI  - Stationary responses of a Rayleigh viscoelastic system with zero barrier impacts
      under external random excitation.
AB  - This paper aims to deal with the stationary responses of a Rayleigh viscoelastic
      system with zero barrier impacts under external random excitation. First, the
      original stochastic viscoelastic system is converted to an equivalent stochastic
      system without viscoelastic terms by approximately adding the equivalent
      stiffness and damping. Relying on the means of non-smooth transformation of state
      variables, the above system is replaced by a new system without an impact term.
      Then, the stationary probability density functions of the system are observed
      analytically through stochastic averaging method. By considering the effects of
      the biquadratic nonlinear damping coefficient and the noise intensity on the
      system responses, the effectiveness of the theoretical method is tested by
      comparing the analytical results with those generated from Monte Carlo
      simulations. Additionally, it does deserve attention that some system parameters
      can induce the occurrence of stochastic P-bifurcation. 

PMID- 27036182
TI  - Chaos of radiative heat-loss-induced flame front instability.
AB  - We are intensively studying the chaos via the period-doubling bifurcation cascade
      in radiative heat-loss-induced flame front instability by analytical methods
      based on dynamical systems theory and complex networks. Significant changes in
      flame front dynamics in the chaotic region, which cannot be seen in the
      bifurcation diagrams, were successfully extracted from recurrence quantification
      analysis and nonlinear forecasting and from the network entropy. The temporal
      dynamics of the fuel concentration in the well-developed chaotic region is much
      more complicated than that of the flame front temperature. It exhibits self
      affinity as a result of the scale-free structure in the constructed visibility
      graph. 

PMID- 27036183
TI  - Complexity in congestive heart failure: A time-frequency approach.
AB  - Reconstruction of phase space is an effective method to quantify the dynamics of
      a signal or a time series. Various phase space reconstruction techniques have
      been investigated. However, there are some issues on the optimal reconstructions
      and the best possible choice of the reconstruction parameters. This research
      introduces the idea of gradient cross recurrence (GCR) and mean gradient cross
      recurrence density which shows that reconstructions in time frequency domain
      preserve more information about the dynamics than the optimal reconstructions in
      time domain. This analysis is further extended to ECG signals of normal and
      congestive heart failure patients. By using another newly introduced measure
      gradient cross recurrence period density entropy, two classes of aforesaid ECG
      signals can be classified with a proper threshold. This analysis can be applied
      to quantifying and distinguishing biomedical and other nonlinear signals. 

PMID- 27036184
TI  - Reynolds number effects on mixing due to topological chaos.
AB  - Topological chaos has emerged as a powerful tool to investigate fluid mixing.
      While this theory can guarantee a lower bound on the stretching rate of certain
      material lines, it does not indicate what fraction of the fluid actually
      participates in this minimally mandated mixing. Indeed, the area in which
      effective mixing takes place depends on physical parameters such as the Reynolds
      number. To help clarify this dependency, we numerically simulate the effects of a
      batch stirring device on a 2D incompressible Newtonian fluid in the laminar
      regime. In particular, we calculate the finite time Lyapunov exponent (FTLE)
      field for three different stirring protocols, one topologically complex (pseudo
      Anosov) and two simple (finite-order), over a range of viscosities. After
      extracting appropriate measures indicative of both the amount of mixing and the
      area of effective mixing from the FTLE field, we see a clearly defined Reynolds
      number range in which the relative efficacy of the pseudo-Anosov protocol over
      the finite-order protocols justifies the application of topological chaos. More
      unexpectedly, we see that while the measures of effective mixing area increase
      with increasing Reynolds number for the finite-order protocols, they actually
      exhibit non-monotonic behavior for the pseudo-Anosov protocol. 

PMID- 27036185
TI  - Dynamic analysis of a buckled asymmetric piezoelectric beam for energy
      harvesting.
AB  - A model of a buckled beam energy harvester is analyzed to determine the phenomena
      behind the transition between high and low power output levels. It is shown that
      the presence of a chaotic attractor is a sufficient condition to predict high
      power output, though there are relatively small areas where high output is
      achieved without a chaotic attractor. The chaotic attractor appears as a product
      of a period doubling cascade or a boundary crisis. Bifurcation diagrams provide
      insight into the development of the chaotic region as the input power level is
      varied, as well as the intermixed periodic windows. 

PMID- 27036186
TI  - Exit from sliding in piecewise-smooth flows: Deterministic vs. determinacy
      breaking.
AB  - The collapse of flows onto hypersurfaces where their vector fields are
      discontinuous creates highly robust states called sliding modes. The way flows
      exit from such sliding modes can lead to complex and interesting behaviour about
      which little is currently known. Here, we examine the basic mechanisms by which a
      flow exits from sliding, either along a switching surface or along the
      intersection of two switching surfaces, with a view to understanding sliding and
      exit when many switches are involved. On a single switching surface, exit occurs
      via tangency of the flow to the switching surface. Along an intersection of
      switches, exit can occur at a tangency with a lower codimension sliding flow, or
      by a spiralling of the flow that exhibits geometric divergence (infinite steps in
      finite time). Determinacy-breaking can occur where a singularity creates a set
      valued flow in an otherwise deterministic system, and we resolve such dynamics as
      far as possible by blowing up the switching surface into a switching layer. We
      show preliminary simulations exploring the role of determinacy-breaking events as
      organizing centres of local and global dynamics. 

PMID- 27036187
TI  - Constructing criteria to diagnose the likelihood of extreme events in the case of
      the electric power grid.
AB  - A set of new criteria for the diagnosis of the possible occurrence of a large
      blackout are constructed, using the output from a model for the dynamics of the
      electric power grid (the OPA model). The approach used is to look for maximum
      values of the Transfer Entropy between time series of the system variables and
      the time series of large blackouts. The best criterion is found by looking at the
      number of overloaded lines at the beginning of the day. 

PMID- 27036188
TI  - Stochastic responses of Van der Pol vibro-impact system with fractional
      derivative damping excited by Gaussian white noise.
AB  - This paper focuses on the study of the stochastic Van der Pol vibro-impact system
      with fractional derivative damping under Gaussian white noise excitation. The
      equations of the original system are simplified by non-smooth transformation. For
      the simplified equation, the stochastic averaging approach is applied to solve
      it. Then, the fractional derivative damping term is facilitated by a numerical
      scheme, therewith the fourth-order Runge-Kutta method is used to obtain the
      numerical results. And the numerical simulation results fit the analytical
      solutions. Therefore, the proposed analytical means to study this system are
      proved to be feasible. In this context, the effects on the response stationary
      probability density functions (PDFs) caused by noise excitation, restitution
      condition, and fractional derivative damping are considered, in addition the
      stochastic P-bifurcation is also explored in this paper through varying the value
      of the coefficient of fractional derivative damping and the restitution
      coefficient. These system parameters not only influence the response PDFs of this
      system but also can cause the stochastic P-bifurcation. 

PMID- 27036189
TI  - Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis.
AB  - Dynamic properties of a nonlinear five-dimensional stoichiometric model of the
      hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated.
      Conditions under which qualitative transitions between dynamic states occur are
      determined by independently varying the rate constants of all reactions that
      constitute the model. Bifurcation types were further characterized using
      continuation algorithms and scale factor methods. Regions of bistability and
      transitions through supercritical Andronov-Hopf and saddle loop bifurcations were
      identified. Dynamic state analysis predicts that the HPA axis operates under
      basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation.
      Dynamic properties of the stress-control axis have not been characterized
      experimentally, but modelling suggests that the proximity to a supercritical
      Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to
      external stimuli and adjust to new conditions and stability, i.e., the capacity
      to return to the original dynamic state afterwards, which is essential for
      maintaining homeostasis. The analysis presented here reflects the properties of a
      low-dimensional model that succinctly describes neurochemical transformations
      underlying the HPA axis. However, the model accounts correctly for a number of
      experimentally observed properties of the stress-response axis. We therefore
      regard that the presented analysis is meaningful, showing how in silico
      investigations can be used to guide the experimentalists in understanding how the
      HPA axis activity changes under chronic disease and/or specific pharmacological
      manipulations. 

PMID- 27036190
TI  - Using heteroclinic orbits to quantify topological entropy in fluid flows.
AB  - Topological approaches to mixing are important tools to understand chaotic fluid
      flows, ranging from oceanic transport to the design of micro-mixers. Typically,
      topological entropy, the exponential growth rate of material lines, is used to
      quantify topological mixing. Computing topological entropy from the direct
      stretching rate is computationally expensive and sheds little light on the source
      of the mixing. Earlier approaches emphasized that topological entropy could be
      viewed as generated by the braiding of virtual, or "ghost," rods stirring the
      fluid in a periodic manner. Here, we demonstrate that topological entropy can
      also be viewed as generated by the braiding of ghost rods following heteroclinic
      orbits instead. We use the machinery of homotopic lobe dynamics, which extracts
      symbolic dynamics from finite-length pieces of stable and unstable manifolds
      attached to fixed points of the fluid flow. As an example, we focus on the
      topological entropy of a bounded, chaotic, two-dimensional, double-vortex cavity
      flow. Over a certain parameter range, the topological entropy is primarily due to
      the braiding of a period-three orbit. However, this orbit does not explain the
      topological entropy for parameter values where it does not exist, nor does it
      explain the excess of topological entropy for the entire range of its existence.
      We show that braiding by heteroclinic orbits provides an accurate computation of
      topological entropy when the period-three orbit does not exist, and that it
      provides an explanation for some of the excess topological entropy when the
      period-three orbit does exist. Furthermore, the computation of symbolic dynamics
      using heteroclinic orbits has been automated and can be used to compute
      topological entropy for a general 2D fluid flow. 

PMID- 27036191
TI  - Discrete-time systems with random switches: From systems stability to networks
      synchronization.
AB  - In this article, we develop some approaches, which enable us to more accurately
      and analytically identify the essential patterns that guarantee the almost sure
      stability of discrete-time systems with random switches. We allow for the case
      that the elements in the switching connection matrix even obey some unbounded and
      continuous-valued distributions. In addition to the almost sure stability, we
      further investigate the almost sure synchronization in complex dynamical networks
      consisting of randomly connected nodes. Numerical examples illustrate that a
      chaotic dynamics in the synchronization manifold is preserved when statistical
      parameters enter some almost sure synchronization region established by the
      developed approach. Moreover, some delicate configurations are considered on
      probability space for ensuring synchronization in networks whose nodes are
      described by nonlinear maps. Both theoretical and numerical results on
      synchronization are presented by setting only a few random connections in each
      switch duration. More interestingly, we analytically find it possible to achieve
      almost sure synchronization in the randomly switching complex networks even with
      very large population sizes, which cannot be easily realized in non-switching but
      deterministically connected networks. 

PMID- 27036192
TI  - Global variational approach to elliptic transport barriers in three dimensions.
AB  - We introduce an approach to identify elliptic transport barriers in three
      dimensional, time-aperiodic flows. Obtained as Lagrangian Coherent Structures
      (LCSs), the barriers are tubular non-filamenting surfaces that form and bound
      coherent material vortices. This extends a previous theory of elliptic LCSs as
      uniformly stretching material surfaces from two-dimensional to three-dimensional
      flows. Specifically, we obtain explicit expressions for the normals of pointwise
      (near-) uniformly stretching material surfaces over a finite time interval. We
      use this approach to visualize elliptic LCSs in steady and time-aperiodic ABC
      type flows. 

PMID- 27036193
TI  - Controllable pulse width of bright similaritons in a tapered graded index
      diffraction decreasing waveguide.
AB  - We obtain the bright similariton solutions for generalized inhomogeneous
      nonlinear Schrodinger equation (GINLSE) which governs the pulse propagation in a
      tapered graded index diffraction decreasing waveguide (DDW). The exact solutions
      have been worked out by employing similarity transformations which involve the
      mapping of the GINLSE to standard NLSE for the certain conditions of the
      parameters. By making use of the exact analytical solutions, we have investigated
      the dynamical behavior of optical similariton pairs and have suggested the
      methods to control them as they propagate through DDW. Moreover, pulse width of
      similariton is controlled through various profiles. These results are helpful to
      understand the similaritons in DDW and can be potentially useful for future
      experiments in optical communications which involve optical amplifiers and long
      haul telecommunication networks. 

PMID- 27036194
TI  - In situ detection of GM1 and GM2 gangliosides using immunohistochemical and
      immunofluorescent techniques for auxiliary diagnosis of canine and feline
      gangliosidoses.
AB  - BACKGROUND: GM1 and GM2 gangliosidoses are progressive neurodegenerative
      lysosomal storage diseases resulting from the excessive accumulation of GM1 and
      GM2 gangliosides in the lysosomes, respectively. The diagnosis of gangliosidosis
      is carried out based on comprehensive findings using various types of specimens
      for histological, ultrastructural, biochemical and genetic analyses. Therefore,
      the partial absence or lack of specimens might have resulted in many undiagnosed
      cases. The aim of the present study was to establish immunohistochemical and
      immunofluorescent techniques for the auxiliary diagnosis of canine and feline
      gangliosidoses, using paraffin-embedded brain specimens stored for a long period.
      RESULTS: Using hematoxylin and eosin staining, cytoplasmic accumulation of pale
      to eosinophilic granular materials in swollen neurons was observed in animals
      previously diagnosed with GM1 or GM2 gangliosidosis. The immunohistochemical and
      immunofluorescent techniques developed in this study clearly demonstrated the
      accumulated material to be either GM1 or GM2 ganglioside. CONCLUSIONS:
      Immunohistochemical and immunofluorescent techniques using stored paraffin
      embedded brain specimens are useful for the retrospective diagnosis of GM1 and
      GM2 gangliosidoses in dogs and cats.

PMID- 27036195
TI  - Heterogeneity in global gene expression profiles between biopsy specimens taken
      peri-surgically from primary ER-positive breast carcinomas.
AB  - BACKGROUND: Gene expression is widely used for the characterisation of breast
      cancers. Variability due to tissue heterogeneity or measurement error or
      systematic change due to peri-surgical procedures can affect measurements but is
      poorly documented. We studied the variability of global gene expression between
      core-cuts of primary ER+ breast cancers and the impact of delays to tissue
      stabilisation due to sample X-ray and of diagnostic core cutting. METHODS: Twenty
      six paired core-cuts were taken immediately after tumour excision and up to 90
      minutes delay due to sample X-ray; 57 paired core-cuts were taken at diagnosis
      and 2 weeks later at surgical excision. Whole genome expression analysis was
      conducted on extracted RNA. Correlations and differences were assessed between
      the expression of individual genes, gene sets/signatures and intrinsic subtypes.
      RESULTS: Twenty-three and 56 sample pairs, respectively, were suitable for
      analysis. The range of correlations for both sample sets were similar with the
      majority being >0.97 in both. Correlations between pairs for 18 commonly studied
      genes were also similar between the studies and mainly with Pearson correlation
      coefficients >0.6 except for a small number of genes, which had a narrow-dynamic
      range (e.g. MKI67, SNAI2). There was no systematic difference in intrinsic
      subtyping between the first and second sample of either set but there was c.15 %
      discordance between the subtype assignments between the pairs, mainly where the
      subtyping of individual samples was less certain. Increases in the expression of
      several stress/early-response genes (e.g. FOS, FOSB, JUN) were found in both
      studies and confirmed findings in earlier smaller studies. Increased expression
      of IL6, IGFBP2 and MYC (by 17 %, 14 % and 44 %, respectively) occurred between
      the samples taken 2 weeks apart and again confirmed findings from an earlier
      study. CONCLUSIONS: There is generally good correlation in gene expression
      between pairs of core-cuts except where genes have a narrow dynamic range.
      Similar correlation coefficients to the average gene expression profiles of
      intrinsic subtype, particularly LumA and LumB, can lead to discordances between
      assigned subtypes. Substantial changes in expression of early-response genes
      occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of
      diagnostic core-cut biopsy. TRIAL REGISTRATION: Trial number CRUK/07/015 . Study
      start date September 2008.

PMID- 27036196
TI  - The compact genome of the plant pathogen Plasmodiophora brassicae is adapted to
      intracellular interactions with host Brassica spp.
AB  - BACKGROUND: The protist Plasmodiophora brassicae is a soil-borne pathogen of
      cruciferous species and the causal agent of clubroot disease of Brassicas
      including agriculturally important crops such as canola/rapeseed (Brassica
      napus). P. brassicae has remained an enigmatic plant pathogen and is a rare
      example of an obligate biotroph that resides entirely inside the host plant cell.
      The pathogen is the cause of severe yield losses and can render infested fields
      unsuitable for Brassica crop growth due to the persistence of resting spores in
      the soil for up to 20 years. RESULTS: To provide insight into the biology of the
      pathogen and its interaction with its primary host B. napus, we produced a draft
      genome of P. brassicae pathotypes 3 and 6 (Pb3 and Pb6) that differ in their host
      range. Pb3 is highly virulent on B. napus (but also infects other Brassica
      species) while Pb6 infects only vegetable Brassica crops. Both the Pb3 and Pb6
      genomes are highly compact, each with a total size of 24.2 Mb, and contain less
      than 2 % repetitive DNA. Clustering of genome-wide single nucleotide
      polymorphisms (SNP) of Pb3, Pb6 and three additional re-sequenced pathotypes
      (Pb2, Pb5 and Pb8) shows a high degree of correlation of cluster grouping with
      host range. The Pb3 genome features significant reduction of intergenic space
      with multiple examples of overlapping untranslated regions (UTRs). Dependency on
      the host for essential nutrients is evident from the loss of genes for the
      biosynthesis of thiamine and some amino acids and the presence of a wide range of
      transport proteins, including some unique to P. brassicae. The annotated genes of
      Pb3 include those with a potential role in the regulation of the plant growth
      hormones cytokinin and auxin. The expression profile of Pb3 genes, including
      putative effectors, during infection and their potential role in manipulation of
      host defence is discussed. CONCLUSION: The P. brassicae genome sequence reveals a
      compact genome, a dependency of the pathogen on its host for some essential
      nutrients and a potential role in the regulation of host plant cytokinin and
      auxin. Genome annotation supported by RNA sequencing reveals significant
      reduction in intergenic space which, in addition to low repeat content, has
      likely contributed to the P. brassicae compact genome.

PMID- 27036197
TI  - Successful treatment of a primary gastric plasmacytoma mimicking intractable
      gastric ulcer by using high-dose dexamethasone therapy: a case report.
AB  - BACKGROUND: Extramedullary plasmacytoma is a plasma cell neoplasm that presents
      as a solitary lesion in soft tissue. Most extramedullary plasmacytomas involve
      the nasopharynx or upper respiratory tract. Primary plasmacytoma of the stomach
      is extremely rare. CASE PRESENTATION: A 78-year-old Korean woman presented with
      epigastric pain for 3 months. She had a history of an intractable gastric ulcer
      despite repeated endoscopic biopsies and appropriate medical therapy for the
      ulcer. She underwent another endoscopy and a biopsy was performed for multiple
      large and deep specimens. Ultimately, primary gastric plasmacytoma was confirmed.
      However, she and her attendant refused standard local radiotherapy or surgical
      resection. She came to our emergency room 3 months later with hematemesis due to
      a large gastric ulcer, despite management with medication for over 3 months at a
      local clinic. We again recommended local radiation or surgical resection.
      However, as she was willing to undergo only medical therapy, she was prescribed
      high-dose dexamethasone. Surprisingly, her ulcer completely regressed and
      remission was maintained for over 1 year. CONCLUSIONS: We report successful
      treatment of a rare primary gastric plasmacytoma mimicking intractable ulcer by
      using high-dose dexamethasone. To the best of our knowledge, this is the first
      reported case successfully treated with only high-dose dexamethasone.

PMID- 27036198
TI  - Identification of genetic variation in the swine toll-like receptors and
      development of a porcine TLR genotyping array.
AB  - BACKGROUND: Toll-like receptors (TLR) are crucial in innate immunity for the
      recognition of a broad range of microbial pathogens and are expressed in multiple
      cell types. There are 10 TLR genes described in the pig genome. RESULTS: With a
      twofold objective i.e. to catalogue genetic variants in porcine TLR genes and
      develop a genotyping array for genetic association studies on immune-related
      traits, we combined targeted sub-genome enrichment and high-throughput sequencing
      to sequence the 10 porcine TLR genes in 266 pigs from 10 breeds and wild boars
      using a DNA-pooling strategy. We identified 306 single nucleotide variants across
      the 10 TLR and 11 populations, 87 of which were novel. One hundred and forty
      seven positions i.e. six stop-gains and 141 non-synonymous substitutions were
      predicted to alter the protein sequence. Three positions were unique to a single
      breed with alternative allele frequencies equal to or higher than 0.5. We
      designed a genotyping array for future applications in genetic association
      studies, with a selection of 126 variants based on their predicted impact on
      protein sequence. Since TLR4, TLR7 and TLR9 were underrepresented in this
      selection, we also included three variants that were located in the 3'UTR of
      these genes. We tested the array by genotyping 214 of the 266 sequenced pigs. We
      found that 93 variants that involved the 10 TLR genes were polymorphic in these
      animals. Twelve of these variants were novel. Furthermore, seven known variants
      that are associated with immune-related phenotypes are present on the array and
      can thus be used to test such associations in additional populations.
      CONCLUSIONS: We identified genetic variations that potentially have an impact on
      the protein sequence of porcine TLR. A genotyping array with 80 non-synonymous,
      10 synonymous and three 3'UTR polymorphisms in the 10 TLR genes is now available
      for association studies in swine populations with measures on immune-related
      traits.

PMID- 27036199
TI  - So, Vegetation Size in Right-sided Endocarditis does not Matter, or does It?

PMID- 27036200
TI  - Festschrift in Honour of David Leslie Ross: A Man for Whom no Electrogram is
      Goliath.

PMID- 27036202
TI  - Characterization of progenitor cells derived from torn human rotator cuff tendons
      by gene expression patterns of chondrogenesis, osteogenesis, and adipogenesis.
AB  - BACKGROUND: It is important to regenerate the tendon-to-bone interface after
      rotator cuff repair to prevent re-tears. The cells from torn human rotator cuff
      were targeted, and their capacity for multilineage differentiation was
      investigated. METHODS: The edges of the rotator cuff were harvested during
      arthroscopic rotator cuff repair from nine patients, minced into pieces, and
      cultured on dishes. Adherent cells were cultured, phenotypically characterized.
      Then expandability, differentiation potential and gene expression were analyzed.
      RESULTS: Flow cytometry revealed that the mesenchymal stem cells (MSC)-related
      markers CD29, CD44, CD105, and CD166 were positive. However, CD14, CD34, and CD45
      were negative. On RT-PCR analyses, the cells showed osteogenic, adipogenic, and
      chondrogenic potential after 3 weeks of culture under the respective
      differentiation conditions. In addition, SOX9, type II collagen, and type X
      collagen expression patterns during chondrogenesis were similar to those of
      endochondral ossification at the enthesis. CONCLUSIONS: The cells derived from
      torn human rotator cuff are multipotent mesenchymal stem cells with the ability
      to undergo multilineage differentiation, suggesting that MSCs form this tissue
      could be regenerative capacity for potential self-repair.

PMID- 27036203
TI  - S1 domain of the porcine epidemic diarrhea virus spike protein as a vaccine
      antigen.
AB  - BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus
      infecting pigs of all ages with high morbidity and mortality among newborn
      piglets. Currently, there is no effective vaccine available to protect the pigs
      from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus
      binding to the cellular receptor and contains a number of neutralizing antibody
      epitopes. Thus, we expressed and produced recombinant S1 protein to protect
      newborn piglets by immunization of sows. METHODS: Affinity tagged PEDV S1 protein
      was expressed in a secretory form in yeast, insect and mammalian cells to
      identify the most suitable production system. Purified recombinant protein was
      analysed by SDS-PAGE, Western blot and deglycosylation assay. A pregnant sow was
      intramuscularly immunized three times with adjuvanted recombinant protein prior
      to farrowing. PEDV-specific immune responses in sera and colostrum of the sow and
      piglets were assayed by ELISA and virus neutralization assays. Piglets were
      challenged orally with PEDV, and clinical parameters were monitored for 6 days
      post-challenge. RESULTS AND CONCLUSION: Of three eukaryotic expression systems
      tested (yeast, insect-cell, and mammalian), expression by HEK-293 T cells gave
      the highest yield of protein that was N-glycosylated and was the most appropriate
      candidate for vaccination. Administration of the subunit vaccine in a sow
      resulted in induction of S1-specific IgG and IgA that were passively transferred
      to the suckling piglets. Also, high virus neutralization titres were observed in
      the serum of the vaccinated sow and its piglets. After PEDV challenge, piglets
      born to the vaccinated sow exhibited less severe signs of disease and
      significantly lower mortality compared to the piglets of a control sow. However,
      there were no significant differences in diarrhea, body weight and virus
      shedding. Thus, vaccination with S1 subunit vaccine failed to provide complete
      protection to suckling piglets after challenge exposure, and further improvements
      are needed for the development of a subunit vaccine that fully protects against
      PEDV infection.

PMID- 27036204
TI  - Bioinformatics analysis of proteomics profiles in senescent human primary
      proximal tubule epithelial cells.
AB  - BACKGROUND: Dysfunction of renal tubule epithelial cells is associated with renal
      tubulointerstitial fibrosis. Exploration of the proteomic profiles of senesced
      tubule epithelial cells is essential to elucidate the mechanism of
      tubulointerstitium development. METHODS: Primary human proximal tubule epithelial
      cells from passage 3 (P3) and passage 6 (P6) were selected for evaluation. EdU
      and SA-beta-galactosidase staining were used to detect cell senescence. p53, p21,
      and p16 were detected by Western blot analysis. Liquid chromatography mass
      spectrometry (LC-MS) was used to examine differentially expressed proteins (DEPs)
      between P6 and P3 cells. The expression of DEPs was examined by Western blot
      analysis. Bioinformatics analysis was performed by protein-protein interaction
      and gene ontology analyses. RESULTS: The majority of tubule cells from passage 6
      (P6) stained positive for SA-beta-galactosidase, whereas passage 3 (P3) cells
      were negative. Senescence biomarkers, including p53, p21, and p16, were
      upregulated in P6 cells relative to P3 cells. EdU staining results showed a lower
      rate of EdU positive cells in P6 cells than in P3 cells. LC-MS was used to
      examine DEPs between P6 and P3 cells. These DEPs are involved in glycolysis,
      response to stress, cytoskeleton regulation, oxidative reduction, ATP binding,
      and oxidative stress. Using Western blot analysis, we validated the down
      regulation of AKR1B1, EEF2, EEF1A1, and HSP90 and the up-regulation of VIM in P6
      cells seen in the LC-MS data. More importantly, we built the molecular network
      based on biological functions and protein-protein interactions and found that the
      DEPs are involved in translation elongation, stress, and glycolysis, and that
      they are all associated with cytoskeleton regulation, which regulates senescent
      cell activities such as apoptosis and EMT in tubule epithelial cells.
      CONCLUSIONS: We explored proteomic profile changes in cell culture-induced
      senescent cells and built senescence-associated molecular networks, which will
      help to elucidate the mechanisms of senescence in human proximal tubule
      epithelial cells.

PMID- 27036205
TI  - Anthelmintic activity of selected ethno-medicinal plant extracts on parasitic
      stages of Haemonchus contortus.
AB  - BACKGROUND: Parasitic roundworms (nematodes) cause substantial morbidity and
      mortality in livestock animals globally, and considerable productivity losses to
      farmers. The control of these nematodes has relied largely on the use of a
      limited number of anthelmintics. However, resistance to many of these these
      anthelmintics is now widespread, and, therefore, there is a need to find new
      drugs to ensure sustained and effective treatment and control into the future.
      METHODS: Recently, we developed a screening assay to test natural, plant extracts
      with known inhibitory effects against the free-living worm Caenorhabditis
      elegans. Using this assay, we assessed here the effects of the extracts on
      motility and development of parasitic larval stages of Haemonchus contortus, one
      of the most important nematodes of small ruminants worldwide. RESULTS: The study
      showed that two of five extracts from Picria fel-terrae Lour. have a significant
      inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and
      development of H. contortus larvae. Although the two extracts originated from the
      same plant, they displayed different levels of inhibition on motility and
      development, which might relate to the presence of various active constituents in
      these extracts, or the same constituents at different concentrations in distinct
      parts of the plant. CONCLUSIONS: These results suggest that extracts from P. fel
      terrae Lour. have promising anthelmintic activity and that more broadly, plant
      extracts are a potential rich source of anthelmintics to combat helminthic
      diseases.

PMID- 27036207
TI  - Case report of hepatic artery dissection secondary to hepatic artery
      pseudoaneurysm after living donor liver transplantation.
AB  - BACKGROUND: Hepatic artery pseudoaneurysm (HAP) and Hepatic artery dissection are
      rare vascular complications after living donor liver transplantation (LDLT),
      which may lead to graft loss and death of the recipients. Conventional gray-scale
      and Doppler ultrasound, as well as contrast-enhanced ultrasound (CEUS), play
      important roles in identifying vascular complications in the early postoperative
      period and during follow-up. We report a case of hepatic artery dissection
      secondary to HAP after LDLT, which was diagnosed and followed for one year by
      ultrasound. To the best of our knowledge, few studies have reported similar cases
      after liver transplantation in the English literature. CASE PRESENTATION: A 43
      year-old man underwent right-lobe LDLT for treatment of a severe acute hepatitis
      B infection and was followed up with ultrasound examinations for one year.
      Conventional gray-scale and Doppler ultrasound combined with contrast-enhanced
      ultrasound (CEUS) accurately revealed the occurrence of HA dissection secondary
      to HAP and accompanied by thrombosis and collateral circulation, as well as
      secondary biliary complications, which provided a prompt diagnosis and guidance
      for the treatment. CONCLUSION: Our case suggests that ultrasound can help detect
      hepatic artery pseudoaneurysm and dissection, as well as secondary biliary
      lesions after LDLT in an accurate and timely manner and provide useful
      information for the treatment chosen. CEUS shows potential as an important
      complementary technique to gray-scale and Doppler ultrasound.

PMID- 27036206
TI  - A phase I study of high-dose rosuvastatin with standard dose erlotinib in
      patients with advanced solid malignancies.
AB  - BACKGROUND: Synergistic cytotoxicity with high-dose statins and erlotinib has
      been demonstrated in preclinical models across a number of tumour types. In this
      phase I study, we evaluated the safety and potential anti-tumour activity of
      escalating doses of rosuvastatin in combination with the standard clinical dose
      of erlotinib in heavily pretreated patients with advanced solid tumours. METHODS:
      This was a single-center, phase I open-label study to determine the safety and
      recommended phase two dose (RPTD) of rosuvastatin in combination with 150 mg/day
      standard dose of erlotinib. Using a 3 + 3 study design and 28-day cycle,
      escalating doses of rosuvastatin from 1 to 8 mg/kg/day * 2 weeks (cycle 1) and 3
      weeks (subsequent cycles) given concurrently with erlotinib were evaluated. In
      order to expand the experience and to gain additional safety and pharmacokinetic
      data, two expansions cohorts using concurrent or alternating weekly dosing
      regimens at the RPTD were also evaluated. RESULTS: All 24 patients enrolled were
      evaluable for toxicity, and 22 for response. The dose-limiting toxicity (DLT) of
      reversible muscle toxicity was seen at the 2 mg/kg/day dose level. Maximal
      tolerated dose (MTD) was determined to be 1 mg/kg/day. Thirty-three percent of
      patients developed at least 1 >= grade 2 muscle toxicity (rhabdomyolysis: 1/24,
      myalgia: 7/24) resulting in one study-related death. Durable stable disease for
      more than 170 days was seen in 25 % of patients that received concurrent
      treatment and were evaluable for response (n = 16). Plasma erlotinib levels on
      study were unaffected by the addition of rosuvastatin. CONCLUSIONS: The observed
      disease stabilization rate of 25 % with combination therapy in this heavily
      pretreated population is encouraging, however, the high levels of muscle
      toxicities observed limited this combination strategy.

PMID- 27036208
TI  - Chromatographic speciation of Cr(III)-species, inter-species equilibrium isotope
      fractionation and improved chemical purification strategies for high-precision
      isotope analysis.
AB  - Chromatographic purification of chromium (Cr), which is required for high
      precision isotope analysis, is complicated by the presence of multiple Cr-species
      with different effective charges in the acid digested sample aliquots. The
      differing ion exchange selectivity and sluggish reaction rates of these species
      can result in incomplete Cr recovery during chromatographic purification. Because
      of large mass-dependent inter-species isotope fractionation, incomplete recovery
      can affect the accuracy of high-precision Cr isotope analysis. Here, we
      demonstrate widely differing cation distribution coefficients of Cr(III)-species
      (Cr(3+), CrCl(2+) and CrCl2(+)) with equilibrium mass-dependent isotope
      fractionation spanning a range of ~10/00/amu and consistent with theory. The
      heaviest isotopes partition into Cr(3+), intermediates in CrCl(2+) and the
      lightest in CrCl2(+)/CrCl3 degrees . Thus, for a typical reported loss of ~25% Cr
      (in the form of Cr(3+)) through chromatographic purification, this translates
      into 185 ppm/amu offset in the stable Cr isotope ratio of the residual sample.
      Depending on the validity of the mass-bias correction during isotope analysis,
      this further results in artificial mass-independent effects in the mass-bias
      corrected (53)Cr/(52)Cr (MU(53)Cr* of 5.2 ppm) and (54)Cr/(52)Cr (MU(54)Cr* of
      13.5 ppm) components used to infer chronometric and nucleosynthetic information
      in meteorites. To mitigate these fractionation effects, we developed strategic
      chemical sample pre-treatment procedures that ensure high and reproducible Cr
      recovery. This is achieved either through 1) effective promotion of Cr(3+) by >5
      days exposure to HNO3H2O2 solutions at room temperature, resulting in >~98% Cr
      recovery for most types of sample matrices tested using a cationic
      chromatographic retention strategy, or 2) formation of Cr(III)-Cl complexes
      through exposure to concentrated HCl at high temperature (>120  degrees C) for
      several hours, resulting in >97.5% Cr recovery using a chromatographic elution
      strategy that takes advantage of the slow reaction kinetics of de-chlorination of
      Cr in dilute HCl at room temperature. These procedures significantly improve
      cation chromatographic purification of Cr over previous methods and allow for
      high-purity Cr isotope analysis with a total recovery of >95%.

PMID- 27036209
TI  - Comprehensive two-dimensional gas chromatographic separations with a temperature
      programmed microfabricated thermal modulator.
AB  - Comprehensive two-dimensional gas chromatography (GC*GC) with a temperature
      programmed microfabricated thermal modulator (MUTM) is demonstrated. The 0.78
      cm(2), 2-stage MUTM chip with integrated heaters and a PDMS coated microchannel
      was placed in thermal contact with a solid-state thermoelectric cooler and
      mounted on top of a bench scale GC. It was fluidically coupled through heated
      interconnects to an upstream first-dimension ((1)D) PDMS-coated capillary column
      and a downstream uncoated capillary or second-dimension ((2)D) PEG-coated
      capillary. A mixture of n-alkanes C6-C10 was separated isothermally and the full
      width-at-half-maximum (fwhm) values of the modulated peaks were assessed as a
      function of the computer-controlled minimum and maximum stage temperatures of
      MUTM, Tmin and Tmax, respectively. With Tmin and Tmax fixed at -25 and 100
      degrees C, respectively, modulated peaks of C6 and C7 had fwhm values<53 ms while
      the modulated peaks of C10 had a fwhm value of 1.3s, due to inefficient re
      mobilization. With Tmin and Tmax fixed at 0 and 210 degrees C, respectively, the
      fwhm value for the modulated C10 peaks decreased to 67 ms, but C6 and C7
      exhibited massive breakthrough. By programming Tmin from -25 to 0 degrees C and
      Tmax from 100 to 220 degrees C, the C6 and C7 peaks had fwhm values<=50 ms, and
      the fwhm for C10 peaks remained<95 ms. Using the latter conditions for the GC*GC
      separation of a sample of unleaded gasoline yielded resolution similar to that
      reported with a commercial thermal modulator. Replacing the PDMS phase in the
      MUTM with a trigonal-tricationic room temperature ionic liquid eliminated the
      bleed observed with the PDMS, but also reduced the capacity for several test
      compounds. Regardless, the demonstrated capability to independently temperature
      program this low resource MUTM enhances its versatility and its promise for use
      in bench-scale GC*GC systems.

PMID- 27036210
TI  - Ionic liquid polymer functionalized carbon nanotubes-doped poly(3,4
      ethylenedioxythiophene) for highly-efficient solid-phase microextraction of
      carbamate pesticides.
AB  - A poly(3,4-ethylenedioxythiophene)-ionic liquid polymer functionalized
      multiwalled carbon nanotubes (PEDOT-PIL/MWCNTs) composite solid-phase
      microextraction (SPME) coating was fabricated by electrodeposition. After being
      dipped in Nafion solution, a Nafion-modified coating was obtained. The outer
      layer Nafion played a crucial role in enhancing the durability and stability of
      the coating, thus it was robust enough for replicated extraction for at least 150
      times without decrease of extraction performance. The Nafion-modified coating
      exhibited much higher sensitivity than commercial coatings for the direct
      extraction of carbamate pesticides in aqueous solutions, due to its strong
      hydrophobic effect and pi-pi affinity based enrichment. When it was used for the
      determination of carbamate pesticides in combination with gas chromatography
      flame ionization detection, good linearity (correlation coefficients higher than
      0.9981), low limits of detection (15.2-27.2 ng/L) and satisfactory precision
      (relative standard deviation <8.2%, n=5) were achieved. The developed method was
      applied to the analysis of four carbamate pesticides in apple and lettuce
      samples, and acceptable recoveries (i.e. 87.5-106.5%) were obtained for the
      standard addition.

PMID- 27036211
TI  - Selective isolation of components from natural volatile oil by countercurrent
      chromatography with cyclodextrins as selective reagent.
AB  - Selective separation of chemical components from seven kinds of volatile oil by
      countercurrent chromatography with three types of cyclodextrins as selective
      reagent was investigated in this work. Preparative separation of chemical
      components from volatile oil is generally quite challenging due to their
      extremely complexity of the composition. A biphasic solvent system n-hexane-0.10
      mol L(-1) cyclodextrin (1:1, v/v) was selected for separation of components from
      volatile oil and three types of cyclodextrins were investigated, including beta
      cyclodexrin, methyl-beta-cyclodexrin and hydroxypropyl-beta-cyclodexrin. All
      kinds of volatile oils are from seven kinds of traditional Chinese herb. Results
      showed that some chemical components could be well separated with high purity
      from each kind of volatile oil using different type of cyclodextrin as selective
      reagent. For example, germacrone and curcumenone could be selectively separated
      from volatile oil of Curcumae Rhizoma with methyl-beta-cyclodexrin and
      hydroxypropyl-beta-cyclodexrin as selector respectively, and other five
      components were selectively separated from volatile oil of Chuanxiong Rhizoma,
      Myristicae Semen, Aucklandiae Radix and Angelicae Sinensis Radix by
      countercurrent chromatography with different cyclodexrin as selective reagent.
      Separation mechanism for separation of components from volatile oil by
      countercurrent chromatography with cyclodextrin as selective reagent was
      proposed. Peak resolution of the present separation method could be greatly
      influenced by the chemical compositions of volatile oil.

PMID- 27036212
TI  - Use of microextraction by packed sorbents and gas chromatography-mass
      spectrometry for the determination of polyamines and related compounds in urine.
AB  - A novel methodology for the determination of ornithine, putrescine, cadaverine,
      spermidine and gamma-amino butyric acid in urine samples has been developed. The
      method uses in situ aqueous derivatization followed by automated microextraction
      by packed sorbent coupled to a gas chromatography-mass spectrometry system
      equipped with a programmed temperature vaporizer. This instrumental configuration
      minimizes sample manipulation due to from the mixing of the reagents, the process
      is completely automated. The analytes were derivatized using ethyl chloroformate
      as derivatization reagent. The reaction occurred in aqueous medium and was
      carried out in 1min in the vial of an autosampler used to perform microextraction
      by packed sorbent. The parameters affecting derivatization, extraction and
      separation were optimized in order to obtain maximum sensitivity. Calibration
      curves were obtained for five calibration levels in three different matrices. All
      the calibration models displayed good linearity, with R(2) values higher than
      0.95. The validity of the models was checked using ANOVA, and it was observed
      that they did not exhibit any lack of fit. Repeatability and reproducibility was
      evaluated, with values below 15% in both cases. LOD and LOQ values were found to
      be in the low MUg/L level. Influence of the matrix was confirmed, thus
      quantification was performed using the standard additions method and
      normalization to IS. The method developed was applied to the analysis of these
      compounds in urine samples from healthy individuals and cancer diagnosed patients
      (Internal Medicine Unit of the Virgen de la Vega Hospital, Salamanca, Spain).
      Significant differences (Mann-Whitney U test) were observed for putrescine and
      ornithine concentrations. 

PMID- 27036213
TI  - Survival prognostic factors in patients undergoing cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy treatment: analysis from a single
      oncological center.
AB  - BACKGROUND: The aim of our study is to analyze survival, treatment-related
      morbidity, and safety in our experience of cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy. METHODS: Sixty-four patients were treated. Survival
      curves were calculated according to the Kaplan-Meier method. Univariate and
      multivariate analyses were done, and Cox's proportional hazard model was used to
      identify significant factors. RESULTS: Global 5-year overall survival was 55%.
      Overall survival was also evaluated according to neutrophils to lymphocytes ratio
      and neutrophils to platelets ratio. Overall survival according to pre-operative
      serum albumin level shows a difference in the two groups (P < 0.05). We observed
      minor or no adverse events in 53 cases (89.8%), while 3 patients (5.1%) showed a
      grade III-IV complication and 3 post-operative deaths (5.1%). Post-operative
      complication also influenced overall survival; patients in whom a minor
      complication occurred had a 3-year overall survival (OS) of 62% vs. a 3-year OS
      of 28% in patients who underwent a major complication (P < 0.1). CONCLUSIONS:
      Hyperthermic intraperitoneal chemotherapy (HIPEC) could be a valid and feasible
      option for selected patients affected by gastrointestinal malignancies'
      peritoneal carcinomatosis. Pre-operative parameters could be evaluated to choose
      patient who could benefit from cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy.

PMID- 27036214
TI  - Mutations analysis of RAB39B gene in Chinese early-onset Parkinson's disease.

PMID- 27036215
TI  - Neuropathic tremor associated with anti-MAG IgM-monoclonal gammopathy and
      prostate adenocarcinoma: Which one is the culprit?

PMID- 27036216
TI  - What surgeons tell patients and what patients want to know before major cancer
      surgery: a qualitative study.
AB  - BACKGROUND: The information surgeons impart to patients and information patients
      want about surgery for cancer is important but rarely examined. This study
      explored information provided by surgeons and patient preferences for information
      in consultations in which surgery for oesophageal cancer surgery was discussed.
      METHODS: Pre-operation consultations in which oesophagectomy was discussed were
      studied in three United Kingdom hospitals and patients were subsequently
      interviewed. Consultations and interviews were audio-recorded, transcribed in
      full and anonymized. Interviews elicited views about the information provided by
      surgeons and patients' preferences for information. Thematic analysis of
      consultation-interview pairs was used to investigate similarities and differences
      in the information provided by surgeons and desired by patients. RESULTS: Fifty
      two audio-recordings from 31 patients and 7 surgeons were obtained (25
      consultations and 27 patient interviews). Six consultations were not recorded
      because of equipment failure and four patients declined an interview. Surgeons
      all provided consistent, extensive information on technical operative details and
      in-hospital surgical risks. Consultations rarely included discussion of the
      longer-term outcomes of surgery. Whilst patients accepted that information about
      surgery and risks was necessary, they really wanted details about long-term
      issues including recovery, impact on quality of life and survival. CONCLUSIONS:
      This study demonstrated a need for surgeons to provide information of importance
      to patients concerning the longer term outcomes of surgery. It is proposed that
      "core information sets" are developed, based on surgeons' and patients' views, to
      use as a minimum in consultations to initiate discussion and meet information
      needs prior to cancer surgery.

PMID- 27036217
TI  - Activity, content, contributors, and influencers of the twitter discussion on
      urologic oncology.
AB  - OBJECTIVES: To analyse the activity, content, contributors, and influencers of
      the Twitter discussion on urologic oncology. MATERIALS AND METHODS: We performed
      a comprehensive quantitative and qualitative Twitter analysis for the hashtags
      #prostatecancer, #bladdercancer, #kidneycancer, and #testicularcancer. Symplur
      was used to analyse activity over different time periods and the top influencers
      of the Twitter discussion. Tweet Archivist and Twitonomy analysis tools were used
      to assess characteristics of content and contributors. RESULTS: Twitter
      discussion on urologic oncology in 2014 contained 100,987 tweets created by
      39,326 participants. Mean monthly tweet activity was 6,603+/-2,183 for
      #prostatecancer, 866+/-923 for #testicularcancer, 457+/-477 for #bladdercancer
      and 401+/-504 for #kidneycancer. Twitter activity increased by 41% in 2013 and by
      122% in 2014. The content analysis detected awareness, cancer, and risk as
      frequently mentioned words in urologic oncology tweets. Prevalently used related
      hashtags were the general hashtag #cancer, awareness hashtags, and the respective
      cancer/urology tag ontology hashtags. Contributors originated from 41 countries
      on 6 continents and had a mean of 5,864+/-4,747 followers. They tweeted from
      platforms on exclusively mobile devices (39%) more frequently than from desktop
      devices (29%). Health care organizations accounted for 58% of the top influencers
      in all cancers. The largest proportion of physicians were among the
      #prostatecancer and #kidneycancer (each 9%) influencers and individual
      contributors were most frequent in the discussion on #kidneycancer (57%) and
      #testicularcancer (50%). CONCLUSION: There is a significant and growing activity
      in the Twitter discussion on urologic oncology, particularly on #prostatecancer.
      The Twitter discussion is global, social, and mobile, and merits attention of
      stakeholders in health care as a promising communication tool.

PMID- 27036218
TI  - Use of mpMRI in active surveillance for localized prostate cancer.
AB  - INTRODUCTION: In an effort to limit prostate cancer (PCa) overdiagnosis and
      overtreatment, which have occurred in response to widespread prostate specific
      antigen testing, numerous strategies aimed at improved risk stratification of
      patients with PCa have evolved. Multiparametric magnetic resonance imaging (MRI)
      is being used in concert with prostate specific antigen testing and prostate
      biopsies to improve sensitivity and specificity of these tests. There are limited
      data on how multiparametric MRI can be incorporated into active surveillance (AS)
      protocols. EVIDENCE ACQUISITION: A PubMed literature search of available English
      language publications on PCa, AS, and MRI was conducted. Appropriate articles
      were selected and included for review. Bibliographies were also used to expand
      our search. EVIDENCE SYNTHESIS: Data from 41 studies were reviewed. AS inclusion
      criteria and protocols varied among studies, as did indications for use of MRI.
      Technological improvements are briefly highlighted. Studies are broadly
      categorized and discussed according to the role of MRI in patient selection,
      disease staging, and monitoring in AS protocols. CONCLUSIONS: Although
      improvements in MRI technology have been useful for biopsy guidance and in the
      diagnosis and staging of PCa, this literature search demonstrates that more
      prospective research is needed, specifically regarding how this promising
      technology can be incorporated into AS protocols.

PMID- 27036219
TI  - Do calcium channel blockers appear to have a protective effect on the development
      of prostate cancer clinically?

PMID- 27036220
TI  - Weight control and behavior rehabilitation in a patient suffering from Prader
      Willi syndrome.
AB  - BACKGROUND: This study reports a case of Prader Willi syndrome (PWS), a genomic
      imprinting disease related to chromosome regions 15q11.2-q13 15, which includes
      hypothalamic dysfunction leading to hyperphagia, obesity, shortness, sleep
      abnormalities. Our case is extremely severe, in comparison to other PWS cases
      described in literature, due to the association with severe emotional and
      psychiatric symptoms: oppositional behaviour, rigidity of thought, skin picking
      and pathological hoarding. CASE PRESENTATION: We described the case of a
      Caucasian male patient suffering from PWS, treated in outpatient care by local
      Mental Health Centre and supported by Social Service, who was admitted to a
      residential rehabilitative facility. After a 2-year follow-up, the patient showed
      a global improvement in symptoms and functioning, as registered by the rating
      scales administered. At the end of observation period, we also reported an
      important improvement in weight control, reducing the risk of obesity and related
      diseases, therefore improving the prognosis of life. CONCLUSION: This case
      highlights the need for long-term, individualized and multi-professional
      treatment in patients suffering from a complex genetic syndrome with both organic
      and psychological alterations, for which medical care setting and pharmacological
      treatments are not sufficient. Clinical observation of this case leads us to
      compare PWS to drug addiction and indirectly endorse the neurophysiological
      hypothesis that food and drugs stimulate the same brain circuits in the limbic
      system.

PMID- 27036221
TI  - Study design to evaluate cognitive behavioral therapy among a diverse sample of
      adults with a first-time DUI offense.
AB  - BACKGROUND: Driving under the influence (DUI) of alcohol is a major public health
      concern, and many individuals continue to drink and drive even after being
      convicted of a DUI offense. Latinos, in particular, are disproportionately likely
      to be arrested for a DUI, have higher rates of recidivism, and are more likely to
      die in alcohol-related accidents than non-Latino Whites. Latinos also experience
      significant disparities in accessing alcohol-related treatment. METHODS/DESIGN:
      This study protocol paper describes a randomized trial of cognitive behavioral
      therapy (CBT) compared to usual care in DUI programs for individuals with a first
      time offense and at-risk drinking. We will utilize a two-group randomized design
      where individuals enrolled in a DUI program with a first-time conviction will be
      randomized to CBT (n = 150) or usual care (n = 150). Participants will be
      assessed at baseline, immediately post-treatment, and 6-months post-treatment.
      Recidivism data will be collected using administrative data within 2 years post
      treatment. DISCUSSION: This project has the potential to benefit a large
      population of vulnerable individuals who are at risk of DUI recidivism. It also
      develops a new model of care by providing treatment in DUI programs to reduce
      disparities associated with poor treatment access. Trial registration
      NCT02588703.

PMID- 27036222
TI  - An alternative nested-PCR assay for the detection of Toxoplasma gondii strains
      based on GRA7 gene sequences.
AB  - Toxoplasma gondii is a widespread parasite able to infect virtually any nucleated
      cells of warm-blooded hosts. In some cases, T. gondii detection using already
      developed PCR primers can be inefficient in routine laboratory tests, especially
      to detect atypical strains. Here we report a new nested-PCR protocol able to
      detect virtually all T. gondii isolates. Analyzing 685 sequences available in
      GenBank, we determine that GRA7 is one of the most conserved genes of T. gondii
      genome. Based on an alignment of 85 GRA7 sequences new primer sets that anneal in
      the highly conserved regions of this gene were designed. The new GRA7 nested-PCR
      assay providing sensitivity and specificity equal to or greater than the gold
      standard PCR assays for T. gondii detection, that amplify the B1 sequence or the
      repetitive 529bp element. 

PMID- 27036223
TI  - Age-period-cohort analysis of infectious disease mortality in urban-rural China,
      1990-2010.
AB  - BACKGROUND: Although a number of studies on infectious disease trends in China
      exist, these studies have not distinguished the age, period, and cohort effects
      simultaneously. Here, we analyze infectious disease mortality trends among urban
      and rural residents in China and distinguish the age, period, and cohort effects
      simultaneously. METHODS: Infectious disease mortality rates (1990-2010) of urban
      and rural residents (5-84 years old) were obtained from the China Health
      Statistical Yearbook and analyzed with an age-period-cohort (APC) model based on
      Intrinsic Estimator (IE). RESULTS: Infectious disease mortality is relatively
      high at age group 5-9, reaches a minimum in adolescence (age group 10-19), then
      rises with age, with the growth rate gradually slowing down from approximately
      age 75. From 1990 to 2010, except for a slight rise among urban residents from
      2000 to 2005, the mortality of Chinese residents experienced a substantial
      decline, though at a slower pace from 2005 to 2010. In contrast to the urban
      residents, rural residents experienced a rapid decline in mortality during 2000
      to 2005. The mortality gap between urban and rural residents substantially
      narrowed during this period. Overall, later birth cohorts experienced lower
      infectious disease mortality risk. From the 1906-1910 to the 1941-1945 birth
      cohorts, the decrease of mortality among urban residents was significantly faster
      than that of subsequent birth cohorts and rural counterparts. CONCLUSIONS: With
      the rapid aging of the Chinese population, the prevention and control of
      infectious disease in elderly people will present greater challenges. From 1990
      to 2010, the infectious disease mortality of Chinese residents and the urban
      rural disparity have experienced substantial declines. However, the re-emergence
      of previously prevalent diseases and the emergence of new infectious diseases
      created new challenges. It is necessary to further strengthen screening,
      immunization, and treatment for the elderly and for older cohorts at high risk.

PMID- 27036224
TI  - Developing a model to assess community-level risk of oral diseases for planning
      public dental services in Australia.
AB  - BACKGROUND: Poor oral health is a chronic condition that can be extremely costly
      to manage. In Australia, publicly funded dental services are provided to
      community members deemed to be eligible-those who are socio-economically
      disadvantaged or determined to be at higher risk of dental disease. Historically
      public dental services have nominally been allocated based on the size of the
      eligible population in a geographic area. This approach has been largely
      inadequate for reducing disparities in dental disease, primarily because the
      approach is treatment-focused, and oral health is influenced by a variety of
      interacting factors. This paper describes the developmental process of a multi
      dimensional community-level risk assessment model, to profile a community's risk
      of poor oral health. METHODS: A search of the evidence base was conducted to
      identify robust frameworks for conceptualisation of risk factors and associated
      performance indicators. Government and other agency websites were also searched
      to identify publicly available data assets with items relevant to oral diseases.
      Data quality and analysis considerations were assessed for the use of mixed data
      sources. RESULTS: Several frameworks and associated indicator sets (twelve
      national and eight state-wide data collections with relevant indicators) were
      identified. Determination of the system inputs for the Model were primarily
      informed by the World Health Organisation's (WHO) operational model for an
      Integrated Oral Health-Chronic Disease Prevention System, and Australia's
      National Oral Health Plan 2004-2013. Data quality and access informed the final
      selection of indicators. CONCLUSIONS: Despite limitations in the quality and
      regularity of data collections, there are numerous data sources available that
      provide the required data inputs for community-level risk assessment for oral
      health. Assessing risk in this way will enhance our ability to deliver
      appropriate public oral health care services and address the uneven distribution
      of oral disease across the social gradient.

PMID- 27036225
TI  - [Adult-onset opsoclonus-myoclonus-ataxia syndrome revealing rubella
      meningoencephalitis].
AB  - INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMS) is a rare clinical syndrome, of
      paraneoplastic infectious, post-infectious, post-vaccinal or idiopathic origin.
      CASE REPORT: We report a 24-year-old young man who presented with gait disorder
      preceded by a febrile rash and retroauricular lymph nodes. Three days before
      admission, he had headache, vertigo, nausea and vomiting followed by gait
      unsteadiness and movement disorders of limbs and eyes. On examination, he had OMS
      syndrome. Brain MRI, total body scan, MIBG scintigraphy, tumor markers and
      onconeural antibodies were normal. Cerebro-spinal fluid (CSF) analysis showed
      lymphocytic meningitis. Positive serum and CSF immunoglobulin M antibody against
      rubella virus was demonstrated. He received acyclovir with full recovery within
      two weeks. We discuss the peculiarities of this association with a literature
      review. CONCLUSION: This observation enlarges the spectrum of neurological
      manifestations of rubella as well as that of OMS etiologies.

PMID- 27036226
TI  - [Hemorrhagic shock revealing multiple digestive microaneurysms in a patient with
      systemic lupus erythematosus: Case report and literature review].
AB  - INTRODUCTION: The vascular disorders in systemic lupus erythematosus (SLE) result
      from various mechanisms and presentations (inflammatory disease or vasculitis,
      atherosclerosis). CASE REPORT: We report on a 34-year-old man with cutaneous,
      articular, neurological and nephrologic SLE. He presented with catastrophic
      haemorrhage on microaneurysm rupture of the left hepatic artery. After blood
      transfusions and immunosuppressive treatments, his condition improves.
      CONCLUSION: Uncommon complication in SLE patients, digestive vasculitis with
      microaneurysms may occur as in polyarteritis nodosa. In the literature, we
      identified 10 additional cases of hepatic microaneurysms in SLE patients. The
      main issue is an earlier diagnosis in order to give appropriate treatment and
      improve prognosis.

PMID- 27036227
TI  - [Lower limb cutaneous lesions].

PMID- 27036228
TI  - Improving care through diagnostic reasoning.

PMID- 27036229
TI  - Adverse drug events in older hospitalized adults: Implications for nursing
      practice.

PMID- 27036231
TI  - Reinforcing and timing properties of water in the schedule-induced drinking
      situation.
AB  - A series of recent studies from our laboratory have added to the preceding
      literature on the potential role of water (in addition to food) as a positive
      reinforcer in the schedule-induced drinking situation, thus suggesting that
      adjunctive behaviors might have motivational properties that make their
      engagement a preferable alternative. It has also been suggested that adjunctive
      behaviors serve as a behavioral clock that helps organisms to estimate time,
      making their engagement motivational, so that they enable more accurate time
      adjustment under temporal schedules. Here, we review some of these experiments on
      conditioned reinforcement and concurrent chains, as well as on temporal learning.
      Data presented in this article suggest that adjunctive behaviors may be a part of
      the behavior patterns maintained by reinforcement, thus serving towards a better
      performance in temporal tasks. 

PMID- 27036230
TI  - Characteristics of gliomas in patients with somatic IDH mosaicism.
AB  - IDH mutations are found in the majority of adult, diffuse, low-grade and
      anaplastic gliomas and are also frequently found in cartilaginous tumors. Ollier
      disease and Maffucci syndrome are two enchondromatosis syndromes characterized by
      the development of multiple benign cartilaginous tumors due to post-zygotic
      acquisition of IDH mutations. In addition to skeletal tumors, enchondromatosis
      patients sometimes develop gliomas. The aim of the present study was to determine
      whether gliomas in enchondromatosis patients might also result from somatic IDH
      mosaicism and whether their characteristics are similar to those of sporadic IDH
      mutated gliomas. For this purpose, we analyzed the characteristics of 6 newly
      diagnosed and 32 previously reported cases of enchondromatosis patients who
      developed gliomas and compared them to those of a consecutive series of 159
      patients with sporadic IDH-mutated gliomas. As was the case with sporadic IDH
      mutated gliomas, enchondromatosis gliomas were frequently located in the frontal
      lobe (54 %) and consisted of diffuse low-grade (73 %) or anaplastic gliomas (21
      %). However, they were diagnosed at an earlier age (25.6 years versus 44 years, p
      < 0.001) and were more frequently multicentric (32 % versus 1 %, p < 0.001) and
      more frequently located within the brainstem than sporadic IDH mutated gliomas
      (21 % versus 1 %, p < 0.001). Their molecular profile was characterized by IDH
      mutations and loss of ATRX expression. In two patients, the same IDH mutation was
      demonstrated in the glioma and in a cartilaginous tumor. In contrast to sporadic
      IDH mutated gliomas, no enchondromatosis glioma harbored a 1p/19q co-deletion
      (0/6 versus 59/123, p = 0.03). The characteristics of gliomas in patients with
      enchondromatosis suggest that these tumors, as cartilaginous tumors, result from
      somatic IDH mosaicism and that the timing of IDH mutation acquisition might
      affect the location and molecular characteristics of gliomas. Early acquisition
      of IDH mutations could shift gliomagenesis towards the brainstem thereby
      mimicking the regional preference of histone mutated gliomas. 

PMID- 27036232
TI  - Counting on your friends: The role of social environment on quantity
      discrimination.
AB  - Quantity discrimination has been established in a range of species. However, most
      demonstrations of quantity discrimination control for social factors by testing
      animals individually. I tested whether sociality affects quantity discrimination
      in the wild by comparing the performances of the highly social Mexican jay (MJ;
      Aphelocoma wollweberi) and the territorial Western scrub jay (WJ; Aphelocoma
      californica). The birds were given a choice between two lines of peanuts that
      differed in initial quantity ranging from 2 vs 8 to 14 vs 16. Their choices were
      recorded until all peanuts were eaten or cached. Whereas non-social WJ selected
      the larger quantity across all the trials significantly more than chance, social
      MJ selected the larger line only when the difference in the number of peanuts
      between lines was small. In MJ, individual choice when selecting the large or
      small quantity was influenced by what line the previous bird had chosen when the
      difference in lines was large, with followers significantly more likely to select
      the smaller quantity. WJ were not significantly affected by the choices of other
      individuals. The only factors that influenced WJ choice were ratio and total
      differences between the two quantities. These results suggests that in certain
      scenarios, both species can discriminate between different quantities. However,
      MJ were greatly influenced by social factors, a previously untested factor, while
      WJ were only influenced by ratio and total difference between the quantities,
      consistent with findings in other species. Overall, this study demonstrates the
      important role of sociality in numerical cognitive performance, a previously
      overlooked factor. 

PMID- 27036233
TI  - On the biophysical regulation of mineral growth: Standing out from the crowd.
AB  - Biogenic mineralization processes are generally regulated by soluble additives
      and insoluble matrices. This endows precise control over the different stages of
      mineralization such as the uptake, transport of mineral precursors as well as the
      subsequent deposition of the mineral phases with consistent compositions and
      morphologies. Programmed in the interactions of organic molecules with different
      precursor species and the fine modulation of the niche environments, a formative
      elegance is reflected in the biological means for crystal formation in comparison
      to the synthetic counterparts. In order to spotlight the role of prevalent
      biophysical environments in the emergence of fascinating materials, we revisit
      biologically modulated mineralization to describe nucleation and crystallization
      under physicochemical highly non-ideal conditions on account of macromolecular
      crowding and the gel-like nature of cellular matrices.

PMID- 27036234
TI  - Impact of thyroid autoimmunity on cumulative delivery rates in in vitro
      fertilization/intracytoplasmic sperm injection patients.
AB  - OBJECTIVE: To predict the impact of thyroid autoimmunity (TAI) on the probability
      of delivery after a defined number of treatment cycles, using analysis of
      cumulative delivery rates in patients with and without TAI. DESIGN: Retrospective
      cohort study performed at the Center for Reproductive Medicine and Department of
      Endocrinology, University Hospital of Brussels, approved by the institutional
      review board of the hospital. SETTING: University hospital. PATIENT(S): All
      patients who started their first IVF/intracytoplasmic sperm injection cycle at
      our fertility center between January 1, 2010 and December 31, 2011 were included.
      MAIN OUTCOME MEASURE(S): Live birth delivery after 25 weeks' gestation was taken
      as the primary endpoint of our study Cumulative delivery rates were calculated
      for both groups until six treatment cycles. INTERVENTION(S): All patients (in
      both groups) received the usual IVF treatment protocols (i.e., antagonist or
      agonist protocol). RESULT(S): In total 2,406 women who consulted our center were
      included. We included 333 patients with TAI and 2019 patients without TAI. In the
      TAI group the crude cumulative delivery rate after six cycles was 47%, whereas
      the expected cumulative delivery rate was 65%. In our control the crude
      cumulative delivery rate after six cycles was 47%, whereas the expected
      cumulative delivery rate was 76%. CONCLUSION(S): Our study did not confirm an
      influence of TAI status in patients undergoing fertility treatment on cumulative
      delivery rates after six IVF/intracytoplasmic sperm injection cycles.

PMID- 27036235
TI  - Nucleotide excision repair deficiency increases levels of acrolein-derived cyclic
      DNA adduct and sensitizes cells to apoptosis induced by docosahexaenoic acid and
      acrolein.
AB  - The acrolein derived cyclic 1,N(2)-propanodeoxyguanosine adduct (Acr-dG), formed
      primarily from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid
      (DHA) under oxidative conditions, while proven to be mutagenic, is potentially
      involved in DHA-induced apoptosis. The latter may contribute to the
      chemopreventive effects of DHA. Previous studies have shown that the levels of
      Acr-dG are correlated with apoptosis induction in HT29 cells treated with DHA.
      Because Acr-dG is shown to be repaired by the nucleotide excision repair (NER)
      pathway, to further investigate the role of Acr-dG in apoptosis, in this study,
      NER-deficient XPA and its isogenic NER-proficient XAN1 cells were treated with
      DHA. The Acr-dG levels and apoptosis were sharply increased in XPA cells, but not
      in XAN1 cells when treated with 125MUM of DHA. Because DHA can induce formation
      of various DNA damage, to specifically investigate the role of Acr-dG in
      apoptosis induction, we treated XPA knockdown HCT116+ch3 cells with acrolein. The
      levels of both Acr-dG and apoptosis induction increased significantly in the XPA
      knockdown cells. These results clearly demonstrate that NER deficiency induces
      higher levels of Acr-dG in cells treated with DHA or acrolein and sensitizes
      cells to undergo apoptosis in a correlative manner. Collectively, these results
      support that Acr-dG, a ubiquitously formed mutagenic oxidative DNA adduct, plays
      a role in DHA-induced apoptosis and suggest that it could serve as a biomarker
      for the cancer preventive effects of DHA.

PMID- 27036236
TI  - Factors influencing health care and service providers' and their respective "at
      risk" populations' adoption of the Air Quality Health Index (AQHI): a qualitative
      study.
AB  - BACKGROUND: The Air Quality Health Index (AQHI) provides air quality and health
      information such that the public can implement health protective behaviours
      (reducing and/or rescheduling outdoor activity) and decrease exposure to outdoor
      air pollution. The AQHI's health messages account for increased risk associated
      with "at risk" populations (i.e. young children, elderly and those with pre
      existing respiratory and/or cardiovascular conditions) who rely on health care
      and service providers for guidance. Using Rogers' Diffusion of Innovations
      theory, our objective with respect to health care and service providers and their
      respective "at risk" populations was to explore: 1) level of AQHI knowledge; 2)
      factors influencing AQHI adoption and; 3) strategies that may increase uptake of
      AQHI, according to city divisions and socioeconomic status (SES). METHODS: Semi
      structured face-to-face interviews with health care (Registered Nurses and
      Certified Respiratory Educators) and service providers (Registered Early
      Childhood Educators) and focus groups with their respective "at risk" populations
      explored barriers and facilitators to AQHI adoption. Participants were selected
      using purposive sampling. Each transcript was analyzed using an Interpretive
      Description approach to identify themes. Analyses were informed by Rogers'
      Diffusion of Innovations theory. RESULTS: Fifty participants (6 health care and
      service providers, 16 parents, 13 elderly, 15 people with existing respiratory
      conditions) contributed to this study. AQHI knowledge, AQHI characteristics and
      perceptions of air quality and health influenced AQHI adoption. AQHI knowledge
      centred on numerical reliance and health protective intent but varied with SES.
      More emphasis on AQHI relevance with respect to health benefits was required to
      stress relative advantage over other indices and reduce index confusion. AQHI
      reporting at a neighbourhood scale was recognized as addressing geographic
      variability and uncertainty in perceived versus measured air quality impacting
      health. Participants predominantly expressed that they relied on sensory cues
      (i.e. feel, sight, taste) to determine when to implement health protective
      behaviours. Time constraints were identified as barriers; whereas local media
      reporting and wearable devices were identified as facilitators to AQHI adoption.
      CONCLUSION: Increasing knowledge, emphasizing relevance, and reporting AQHI
      information at a neighbourhood scale via local media sources and wearable devices
      may facilitate AQHI adoption while accounting for SES differences.

PMID- 27036237
TI  - Bayesian source localization with uncertain Green's function in an uncertain
      shallow water ocean.
AB  - Matched-field acoustic source localization is a challenging task when
      environmental properties of the oceanic waveguide are not precisely known. Errors
      in the assumed environment (mismatch) can cause severe degradations in
      localization performance. This paper develops a Bayesian approach to improve
      robustness to environmental mismatch by considering the waveguide Green's
      function to be an uncertain random vector whose probability density accounts for
      environmental uncertainty. The posterior probability density is integrated over
      the Green's function probability density to obtain a joint marginal probability
      distribution for source range and depth, accounting for environmental uncertainty
      and quantifying localization uncertainty. Because brute-force integration in high
      dimensions can be costly, an efficient method is developed in which the multi
      dimensional Green's function integration is approximated by one-dimensional
      integration over a suitably defined correlation measure. An approach to
      approximate the Green's function covariance matrix, which represents the
      environmental mismatch, is developed based on modal analysis. Examples are
      presented to illustrate the method and Monte-Carlo simulations are carried out to
      evaluate its performance relative to other methods. The proposed method gives
      efficient, reliable source localization and uncertainties with improved
      robustness toward environmental mismatch. 

PMID- 27036239
TI  - Heterogeneity of vocal sac inflation patterns in Odorrana tormota plays a role in
      call diversity.
AB  - Male concave-eared torrent frogs (Odorrana tormota) can emit at least eight
      distinct call-types. However, the mechanisms by which they are produced are not
      fully understood. Anatomical analysis revealed that the vocal sacs of male O.
      tormota comprise two physically distinct compartments (pars lateralis and pars
      ventralis), residing on two sides of the vocal slits. The goal of the present
      study was to test the hypothesis that the two compartments play a role in the
      production of the diverse call-types. For this, audio and video recordings of
      male vocalizations were made, and sounds were analyzed afterwards. Results showed
      that the vocal sac inflation pattern was heterogeneous, and the call duration was
      a major factor determining the differential inflation patterns. Short call-types
      (duration <200 ms) involved inflation of one of the compartments only; those
      having a fundamental frequency (F0) of >5000 Hz involved inflation of pars
      lateralis only, whereas those with an F0 of <4000 Hz (tone-pips and "infant"
      calls) involved inflation of pars ventralis only. Long call-types (duration >200
      ms), e.g., shallow frequency modulation calls, staccato calls, and long calls,
      involved inflation of both compartments of the vocal sacs. These results give
      support to the working hypothesis.

PMID- 27036240
TI  - Analytical approach to transforming filter design for sound field recording and
      reproduction using circular arrays with a spherical baffle.
AB  - A sound field recording and reproduction method using circular arrays of
      microphones and loudspeakers with a spherical baffle is proposed. The spherical
      baffle is an acoustically rigid object on which the microphone array is mounted.
      The driving signals of the loudspeakers must be obtained from the signals
      received by the microphones. A transform filter for this signal conversion is
      analytically derived, which is referred to as the wave field reconstruction
      filter. The proposed method using a spherical baffle is compared with methods
      using an array of directional microphones and a microphone array mounted on a
      cylindrical baffle. Numerical simulations indicated that the proposed method is
      advantageous for sound field recording and reproduction compared with the other
      two methods. The results of measurement experiments in a real environment are
      also demonstrated. 

PMID- 27036241
TI  - Effects of a consistent target or masker voice on target speech intelligibility
      in two- and three-talker mixtures.
AB  - When the spatial location or identity of a sound is held constant, it is not
      masked as effectively by competing sounds. This suggests that experience with a
      particular voice over time might facilitate perceptual organization in
      multitalker environments. The current study examines whether listeners benefit
      from experience with a voice only when it is the target, or also when it is a
      masker, using diotic presentation and a closed-set task (coordinate response
      measure). A reliable interaction was observed such that, in two-talker mixtures,
      consistency of masker or target voice over 3-7 trials significantly benefited
      target recognition performance, whereas in three-talker mixtures, target, but not
      masker, consistency was beneficial. Overall, this work suggests that voice
      consistency improves intelligibility, although somewhat differently when two
      talkers, compared to three talkers, are present, suggesting that consistent-voice
      information facilitates intelligibility in at least two different ways. Listeners
      can use a template-matching strategy to extract a known voice from a mixture when
      it is the target. However, consistent-voice information facilitates segregation
      only when two, but not three, talkers are present. 

PMID- 27036242
TI  - Automated estimation of the truncation of room impulse response by applying a
      nonlinear decay model.
AB  - Noise represents one of the most significant disturbances in measured room
      impulse responses (RIRs), and it has a potentially large impact on evaluation of
      the decay parameters. In order to reduce noise effects, various methods have been
      applied, including truncation of an RIR. In this paper, a procedure for the
      response truncation based on a model of RIR (nonlinear decay model) is presented.
      The model is represented by an exponential decay plus stationary noise. Unknown
      parameters of the model are calculated by an optimization that minimizes the
      difference between the curve generated by the model and the target one of the
      response to be truncated. Different curves can be applied in the optimization
      absolute value of the RIR, logarithmic decay curve, and Schroeder curve obtained
      by the backward integration of the RIR. The proposed procedure is tested on
      various synthesized and measured impulse responses. It is compared with the
      procedure taken from the literature, often applied in practice. 

PMID- 27036243
TI  - Design and implementation of a space domain spherical microphone array with
      application to source localization and separation.
AB  - In this paper, four delay-and-sum (DAS) beamformers formulated in the modal
      domain and the space domain for open and solid spherical apertures are examined
      through numerical simulations. The resulting beampatterns reveal that the
      mainlobe of the solid spherical DAS array is only slightly narrower than that of
      the open array, whereas the sidelobes of the modal domain array are more
      significant than those of the space domain array due to the discrete
      approximation of continuous spherical Fourier transformation. To verify the
      theory experimentally, a three-dimensionally printed spherical array on which 32
      micro-electro-mechanical system microphones are mounted is utilized for
      localization and separation of sound sources. To overcome the basis mismatch
      problem in signal separation, source localization is first carried out using
      minimum variance distortionless response beamformer. Next, Tikhonov
      regularization (TIKR) and compressive sensing (CS) are employed to extract the
      source signal amplitudes. Simulations and experiments are conducted to validate
      the proposed spherical array system. Objective perceptual evaluation of speech
      quality test and a subjective listening test are undertaken in performance
      evaluation. The experimental results demonstrate better separation quality
      achieved by the CS approach than by the TIKR approach at the cost of
      computational complexity. 

PMID- 27036244
TI  - Eigenfunction approach to the Green's function parabolic equation in outdoor
      sound: A tutorial.
AB  - Understanding the physics and mathematics underlying a computational algorithm
      such as the Green's function parabolic equation (GFPE) is both useful and
      worthwhile. To this end, the present article aims to give a more widely
      accessible derivation of the GFPE algorithm than was given originally by Gilbert
      and Di [(1993). J. Acoust. Soc. Am. 94, 2343-2352]. The present derivation, which
      uses mathematics familiar to most engineers and physicists, begins with the
      separation of variables method, a basic and well-known approach for solving
      partial differential equations. The method leads naturally to eigenvalue
      eigenfunction equations. A step-by-step analysis arrives at relatively simple,
      analytic expressions for the horizontal and vertical eigenfunctions, which are
      sinusoids plus a surface wave. The eigenfunctions are superposed in an
      eigenfunction expansion to yield a one-way propagation solution. The one-way
      solution is generalized to obtain the GFPE algorithm. In addition, and equally
      important, the eigenfunctions are used to give concrete meaning to abstract
      operator solutions for one-way acoustic propagation. By using an eigenfunction
      expansion of the acoustic field, together with an operator solution, one can
      obtain the GFPE algorithm very directly and concisely. 

PMID- 27036245
TI  - Small acoustically forced symmetric bodies in viscous fluids.
AB  - The total force exerted on a small rigid body by an acoustic field in a viscous
      fluid is addressed analytically in the limit where the typical size of the
      particle is smaller than both the viscous diffusion length scale and the acoustic
      wavelength. In this low-frequency limit, such a force can be calculated provided
      the effect of the acoustic steady streaming is negligible. Using the Eulerian
      linear expansion of Lagrangian hydrodynamic quantities (velocity and pressure),
      the force on a small solid sphere free to move in an acoustic field is first
      calculated in the case of progressive and standing waves, and it is compared to
      past results. The proposed method is then extended to the case of more complex
      shapes with three planes of symmetry. For a symmetric body oriented with one of
      its axis along the wave direction, the acoustic force exerted by a progressive
      wave is affected by the particle shape at leading order. In contrast, for a
      standing wave (with the same orientation), the force experienced by the particle
      at leading order is the same as the one experienced by a sphere of same volume
      and density. 

PMID- 27036246
TI  - Uncertainties of reverberation time estimation via adaptively identified room
      impulse responses.
AB  - This paper investigates the reverberation time estimation methods which employ
      backward integration of adaptively identified room impulse responses (RIRs). Two
      kinds of conditions are considered; the first is the "ideal condition" where the
      anechoic and reverberant signals are both known a priori so that the RIRs can be
      identified using system identification methods. The second is that only the
      reverberant speech signal is available, and blind identification of the RIRs via
      dereverberation is employed for reverberation time estimation. Results show that
      under the "ideal condition," the average relative errors in 7 octave bands are
      less than 2% for white noise and 15% for speech, respectively, when both the
      anechoic and reverberant signals are available. In contrast, under the second
      condition, the average relative errors of the blindly identified RIR-based
      reverberation time estimation are around 20%-30% except the 63 Hz octave band.
      The fluctuation of reverberation times estimated under the second condition is
      more severe than that under the ideal condition and the relative error for low
      frequency octave bands is larger than that for high octave bands under both
      conditions. 

PMID- 27036247
TI  - Auditory evoked potentials in the auditory system of a beluga whale
      Delphinapterus leucas to prolonged sound stimuli.
AB  - The effects of prolonged (up to 1500 s) sound stimuli (tone pip trains) on evoked
      potentials (the rate following response, RFR) were investigated in a beluga
      whale. The stimuli (rhythmic tone pips) were of frequencies of 45, 64, and 90 kHz
      at levels from 20 to 60 dB above threshold. Two experimental protocols were used:
      short- and long-duration. For the short-duration protocol, the stimuli were 500
      ms-long pip trains that repeated at a rate of 0.4 trains/s. For the long-duration
      protocol, the stimuli were continuous pip successions lasting up to 1500 s. The
      RFR amplitude gradually decreased by three to seven times from 10 ms to 1500 s of
      stimulation. Decrease of response amplitude during stimulation was approximately
      proportional to initial (at the start of stimulation) response amplitude.
      Therefore, even for low stimulus level (down to 20 dB above the baseline
      threshold) the response was never suppressed completely. The RFR amplitude decay
      that occurred during stimulation could be satisfactorily approximated by a
      combination of two exponents with time constants of 30-80 ms and 3.1-17.6 s. The
      role of adaptation in the described effects and the impact of noise on the
      acoustic orientation of odontocetes are discussed. 

PMID- 27036248
TI  - Global examination of the wind-dependence of very low frequency underwater
      ambient noise.
AB  - Ocean surface winds play a key role in underwater ambient noise generation. One
      particular frequency band of interest is the infrasonic or very low frequency
      (VLF) band from 1 to 20 Hz. In this spectral band, wind generated ocean surface
      waves interact non-linearly to produce acoustic waves, which couple into the
      seafloor to generate microseisms, as explained by the theory developed by Longuet
      Higgins. This study examines long term data sets in the VLF portion of the
      ambient noise spectrum, collected by the hydroacoustic systems of the
      Comprehensive Nuclear-Test Ban Treaty Organization in the Atlantic, Pacific, and
      Indian Oceans. Three properties of the noise field were examined: (a) the
      behavior of the acoustic spectrum slope from 1 to 5 Hz, (b) correlation of noise
      levels and wind speeds, and (c) the autocorrelation behavior of both the noise
      field and the wind. Analysis results indicate the spectrum slope is site
      dependent, and for both correlation methods, a high correlation between wind and
      the noise field in the 1-5 Hz band.

PMID- 27036249
TI  - Road traffic noise impact assessment in a breeding colony of cinereous vultures
      (Aegypius monachus) in Spain.
AB  - There is a global and growing concern with regard to anthropogenic noise impact
      on wildlife and natural habitats, but it is difficult to find consensus regarding
      scoping and assessment tools. This study adapts noise mapping procedures, common
      to most European countries, to a low traffic road (below 1000 vehicles per day)
      noise impact assessment in a breeding colony of the largest bird of prey in
      Europe. Results show that nest sites are located avoiding road traffic Leq levels
      higher than 40 dB. This means a road-effect zone of up to 500 m width from road
      margins, which previous scientific literature only refers in cases of traffic
      volumes higher than 10,000 vehicles per day. This finding is a noticeable impact
      by road traffic noise that reduces the breeding potential habitat more than 11%
      within the study area. This work shows the feasibility of expanding common
      methods and mapping tools for assessing and managing environmental noise in
      protected areas, which has worthwhile implications for both acoustics and
      conservation.

PMID- 27036250
TI  - Perception of contrastive bi-syllabic lexical stress in unaccented and accented
      words by younger and older listeners.
AB  - This study examined the ability of older and younger listeners to perceive
      contrastive syllable stress in unaccented and Spanish-accented cognate bi
      syllabic English words. Younger listeners with normal hearing, older listeners
      with normal hearing, and older listeners with hearing impairment judged
      recordings of words that contrasted in stress that conveyed a noun or verb form
      (e.g., CONduct/conDUCT), using two paradigms differing in the amount of semantic
      support. The stimuli were spoken by four speakers: one native English speaker and
      three Spanish-accented speakers (one moderately and two mildly accented). The
      results indicate that all listeners showed the lowest accuracy scores in
      responding to the most heavily accented speaker and the highest accuracy in
      judging the productions of the native English speaker. The two older groups
      showed lower accuracy in judging contrastive lexical stress than the younger
      group, especially for verbs produced by the most accented speaker. This general
      pattern of performance was observed in the two experimental paradigms, although
      performance was generally lower in the paradigm without semantic support. The
      findings suggest that age-related difficulty in adjusting to deviations in
      contrastive bi-syllabic lexical stress produced with a Spanish accent may be an
      important factor limiting perception of accented English by older people. 

PMID- 27036251
TI  - Low-frequency signals produced by Northeast Atlantic killer whales (Orcinus
      orca).
AB  - Killer whale acoustic behavior has been extensively investigated; however, most
      studies have focused on pulsed calls and whistles. This study reports the
      production of low-frequency signals by killer whales at frequencies below 300 Hz.
      Recordings were made in Iceland and Norway when killer whales were observed
      feeding on herring and no other marine mammal species were nearby. Low-frequency
      sounds were identified in Iceland and ranged in duration between 0.14 and 2.77 s
      and in frequency between 50 and 270 Hz, well below the previously reported lower
      limit for killer whale tonal sounds of 500 Hz. Low-frequency sounds appeared to
      be produced close in time to tail slaps, which are indicative of feeding
      attempts, suggesting that these sounds may be related to a feeding context.
      However, their precise function is unknown, and they could be the by-product of a
      non-vocal behavior rather than a vocal signal deliberately produced by the
      whales. Although killer whales in Norway exhibit similar feeding behavior, this
      sound has not been detected in recordings from Norway to date. This study
      suggests that, like other delphinids, killer whales produce low-frequency sounds,
      but further studies will be required to understand whether similar sounds exist
      in other killer whale populations.

PMID- 27036252
TI  - Relationships between non-acoustic factors and subjective reactions to floor
      impact noise in apartment buildings.
AB  - The aim of this study was to provide an understanding of how residents in
      apartment buildings perceive and react to impact sounds coming from the upstairs
      neighbours' dwellings. Based on existing theoretical and empirical studies on
      environmental noise, a conceptual model was developed to explain relationships
      among noise annoyance and non-acoustic factors. The model was then tested using
      structural equation modelling with survey data from residents living in apartment
      buildings (N = 487). The findings showed that the conceptual model was consistent
      with other models developed for environmental noises. The results indicated that
      annoyance induced by floor impact noise was associated with perceived
      disturbance, coping, and self-reported health complaints. Noise sensitivity had a
      direct impact on perceived disturbance and an indirect impact on annoyance, and
      moderating variables affected the non-acoustic factors. Exposure to footstep
      noises increased the impact size of noise sensitivity to disturbance.
      Predictability, marital status, and house ownership were found to influence the
      relationship between attitudes towards authorities and coping. In addition, a
      negative attitude towards neighbours (i.e., the noise source) moderated the
      positive relationship between annoyance and coping.

PMID- 27036253
TI  - Sound field reconstruction using a spherical microphone array.
AB  - A method is presented that makes it possible to reconstruct an arbitrary sound
      field based on measurements with a spherical microphone array. The proposed
      method (spherical equivalent source method) makes use of a point source expansion
      to describe the sound field on the rigid spherical array, from which it is
      possible to reconstruct the sound field over a three-dimensional domain,
      inferring all acoustic quantities: sound pressure, particle velocity, and sound
      intensity. The problem is formulated using a Neumann Green's function that
      accounts for the presence of the rigid sphere in the medium. One can reconstruct
      the total sound field, or only the incident part, i.e., the scattering introduced
      by the sphere can be removed, making the array virtually transparent. The method
      makes it possible to use sequential measurements: different measurement positions
      can be combined, providing an extended measurement area consisting of an array of
      spheres, and the sound field at any point of the source-free domain can be
      estimated, not being restricted to spherical surfaces. Because it is formulated
      as an elementary wave model, it allows for diverse solution strategies (least
      squares, l1-norm minimization, etc.), revealing an interesting perspective for
      further work. 

PMID- 27036254
TI  - Backward waves with double zero-group-velocity points in a liquid-filled pipe.
AB  - Hollow cylinders often exhibit backward propagation modes whose group and phase
      velocities have opposite directions, and these exhibit a minimum possible
      frequency at which the group velocity vanishes at a nonzero wavenumber. These
      zero-group-velocity (ZGV) points are associated with resonant conditions in the
      medium. On the basis of ZGV resonances, a non-contact and laser ultrasound
      technique has been developed to measure elastic constants of hollow pipes. This
      paper provides a theoretical and numerical investigation of the influence of the
      contained liquid on backward waves and associated ZGV modes, in order to explore
      whether this ZGV technique is suitable for in-service non-destructive evaluations
      of liquid-filled pipes. Dispersion spectra and excitation properties have been
      analyzed. It is found that the presence of the liquid causes an increased number
      of backward modes and ZGVs which are highly excitable by a point source. In
      addition, several guided modes twice undergo a change of sign in the slopes of
      their dispersion curves, leading to two ZGV points. This phenomenon of double
      ZGVs in one backward wave, which is caused by strong mode repulsions, has not
      been found in isotropic hollow cylinders, but it can be observed in a fluid
      filled thin-walled pipe. 

PMID- 27036255
TI  - Inherent envelope fluctuations in forward maskers: Effects of masker-probe delay
      for listeners with normal and impaired hearing.
AB  - Forward-masked thresholds increase as the magnitude of inherent masker envelope
      fluctuations increase for both normal-hearing (NH) and hearing-impaired (HI)
      adults for a short masker-probe delay (25 ms). The slope of the recovery from
      forward masking is shallower for HI than for NH listeners due to reduced cochlear
      nonlinearities. However, effects of hearing loss on additional masking due to
      inherent envelope fluctuations across masker-probe delays remain unknown. The
      current study assessed effects of hearing loss on the slope and amount of
      recovery from forward maskers that varied in inherent envelope fluctuations.
      Forward-masked thresholds were measured at 2000 and 4000 Hz, for masker-probe
      delays of 25, 50, and 75 ms, for NH and HI adults. Four maskers at each center
      frequency varied in inherent envelope fluctuations: Gaussian noise (GN) or low
      fluctuation noise (LFN), with 1 or 1/3 equivalent rectangular bandwidths (ERBs).
      Results suggested that slopes of recovery from forward masking were shallower for
      HI than for NH listeners regardless of masker fluctuations. Additional masking
      due to inherent envelope fluctuations was greater for HI than for NH listeners at
      longer masker-probe delays, suggesting that inherent envelope fluctuations are
      more disruptive for HI than for NH listeners for a longer time course.

PMID- 27036256
TI  - Understanding frequency-compressed Mandarin sentences: Role of vowels.
AB  - Frequency compression (FC) is an effective alternative to conventional
      amplification for patients with severe-to-profound middle- and high-frequency
      hearing loss and with some residual low frequency hearing. The present work
      investigated the underlying factors accounting for the intelligibility of FC
      processed speech. Eighteen normal-hearing participants listened to FC-processed
      Mandarin sentences, and testing conditions included two compression strategies
      (i.e., linear and nonlinear), four degrees of compression, and two segmental
      conditions (i.e., vowel-center and vowel-onset). Results showed that the
      nonlinear strategy outperformed the linear strategy in enhancing the
      intelligibility of FC-processed sentences. A small frequency range of source
      compression region involved a lesser degree of compression, and favored a higher
      intelligibility score. Vowel segments carried a large amount of intelligibility
      information contained in nonlinearly frequency-compressed sentences, but could
      not fully account for the intelligibility improvement from nonlinear frequency
      compression. The intelligibility benefit of FC-processed Mandarin sentences may
      be partially attributed to the additional F1-F2 transitional spectral envelope
      cue provided by nonlinear FC with the F1-included spectral region preserved. 

PMID- 27036257
TI  - Concert halls with strong and lateral sound increase the emotional impact of
      orchestra music.
AB  - An audience's auditory experience during a thrilling and emotive live symphony
      concert is an intertwined combination of the music and the acoustic response of
      the concert hall. Music in itself is known to elicit emotional pleasure, and at
      best, listening to music may evoke concrete psychophysiological responses.
      Certain concert halls have gained a reputation for superior acoustics, but
      despite the continuous research by a multitude of objective and subjective
      studies on room acoustics, the fundamental reason for the appreciation of some
      concert halls remains elusive. This study demonstrates that room acoustic effects
      contribute to the overall emotional experience of a musical performance. In two
      listening tests, the subjects listen to identical orchestra performances rendered
      in the acoustics of several concert halls. The emotional excitation during
      listening is measured in the first experiment, and in the second test, the
      subjects assess the experienced subjective impact by paired comparisons. The
      results showed that the sound of some traditional rectangular halls provides
      greater psychophysiological responses and subjective impact. These findings
      provide a quintessential explanation for these halls' success and reveal the
      overall significance of room acoustics for emotional experience in music
      performance. 

PMID- 27036258
TI  - Quantification of the effects of audible rattle and source type on the human
      response to environmental vibration.
AB  - The present research quantifies the influence of source type and the presence of
      audible vibration-induced rattle on annoyance caused by vibration in residential
      environments. The sources of vibration considered are railway and the
      construction of a light rail system. Data were measured in the United Kingdom
      using a socio-vibration survey (N = 1281). These data are analyzed using ordinal
      logit models to produce exposure-response relationships describing community
      annoyance as a function of vibration exposure. The influence of source type and
      the presence of audible vibration-induced rattle on annoyance are investigated
      using dummy variable analysis, and quantified using odds-ratios and community
      tolerance levels. It is concluded that the sample population is more likely to
      express higher levels of annoyance if the vibration source is construction
      compared to railway, and if vibration-induced rattle is audible.

PMID- 27036259
TI  - The import of within-listener variability to understanding the precedence effect.
AB  - The purpose of this study was to gather behavioral data concerning the precedence
      effect as manifested by the localization-dominance of the leading elements of
      compound stimuli. This investigation was motivated by recent findings of
      Shackleton and Palmer [(2006). J. Assoc. Res. Otolaryngol. 7, 425-442], who
      measured the electro-physiological responses of single units in the inferior
      colliculus of the guinea pig. The neural data from Shackleton and Palmer
      indicated that processing of binaural cues like those relevant to understanding
      localization dominance is greatly affected by internal, neural noise. In order to
      evaluate the generality of their physiological results to human perception, the
      present study measured localization dominance so that behavioral responses within
      and across sets of samples (i.e., tokens) of frozen noises could be compared.
      Conceptually consistent with Shackleton and Palmer's neural data, the variability
      of perceived intracranial lateral positions produced by repeated presentations of
      the same tokens of noise was greater than the variability of intracranial lateral
      positions measured across different tokens of noise. This was true for each of
      the four individual listeners and for each of the 72 stimulus conditions studied.
      Thus, measured either neuro-physiologically (Shackleton and Palmer, 2006) or
      behaviorally (this study), the import of within-listener variability appears to
      be a general, intrinsic aspect of binaural information processing. 

PMID- 27036260
TI  - Effect of modulation depth, frequency, and intermittence on wind turbine noise
      annoyance.
AB  - Amplitude modulation (AM) may be an important factor for the perceived annoyance
      of wind turbine noise (WTN). Two AM types, typically referred to as "normal AM"
      (NAM) and "other AM" (OAM), characterize WTN AM, OAM corresponding to having
      intermittent periods with larger AM depth in lower frequency regions than NAM.
      The extent to which AM depth, frequency, and type affect WTN annoyance remains
      uncertain. Moreover, the temporal variations of WTN AM have often not been
      considered. Here, realistic stimuli accounting for such temporal variations were
      synthesized such that AM depth, frequency, and type, while determined from real
      on-site recordings, could be varied systematically. Listening tests with both
      original and synthesized stimuli showed that a reduction in mean AM depth across
      the spectrum led to a significant decrease in annoyance. When the spectrotemporal
      characteristics of the original far-field stimuli and the temporal AM variations
      were taken into account, the effect of AM frequency remained limited and the
      presence of intermittent OAM periods did not affect annoyance. These findings
      suggest that, at a given overall level, the AM depth of NAM periods is the most
      crucial AM parameter for WTN annoyance. 

PMID- 27036261
TI  - A robust and passive method for geometric calibration of large arrays.
AB  - This paper presents a complete strategy for the geometry estimation of large
      microphone arrays of arbitrary shape. Largeness is intended here in both number
      of microphones (hundreds) and size (few meters). Such arrays can be used for
      various applications in open or confined spaces like acoustical imaging, source
      identification, or speech processing. For so large array systems, measuring the
      geometry by hand is impractical. Therefore a blind passive method is proposed. It
      is based on the analysis of the background acoustic noise, supposed to be a
      diffuse field. The proposed strategy is a two-step process. First the pairwise
      microphone distances are identified by matching their measured coherence function
      to the one predicted by the diffuse field theory. Second, a robust
      multidimensional scaling (MDS) algorithm is adapted and implemented. It takes
      advantage of local characteristics to reduce the set of distances and infer the
      geometry of the array. This work is an extension of previous studies, and it
      overcomes unsolved drawbacks. In particular it deals efficiently with the
      outliers known to ruin standard MDS algorithms. Experimental proofs of this
      ability are presented by treating the case of two arrays. They show that the
      proposed improvements manage large spatial arrays. 

PMID- 27036262
TI  - The acoustical role of vocal tract in the horseshoe bat, Rhinolophus pusillus.
AB  - The sound field distribution in the vocal tract with a single sound source in the
      glottis and the transfer function of the supraglottal vocal tract of the
      horseshoe bat, Rhinolophus pusillus, have been obtained using the finite-element
      method (FEM) technique. The models of vocal tracts used for FEM calculation are
      constructed by tomography scanning. These models are used to set up a finite
      element model for calculating the sound field distribution by loading the unit
      sound source in the glottis. By changing the frequency of the unit sound source,
      the frequency response was figured out and the acoustic role of vocal tract
      chambers was examined by obtaining the transfer function and sound pressure
      distribution before and after filling the chambers using voxels. Sound pressures
      in the trachea and nostrils are recorded and some analysis of the acoustics of
      the subglottal and vocal tract was made to find the function of the construction
      in the vocal tract and subglottal parts. The results show nasal chambers can
      effectively improve the Q (quality factor) value near the second harmonic, and
      alternate the sound distribution in the supraglottal part. Whereas the tracheal
      chambers can reduce the amplitude second harmonic in the subglottal part, its
      function is like a notch filter which can block the second harmonic component of
      the back propagation sound under the glottis. 

PMID- 27036263
TI  - Speech rate and pitch characteristics of infant-directed speech: Longitudinal and
      cross-linguistic observations.
AB  - The speech rate and pitch (F0) characteristics of naturalistic, longitudinally
      recorded infant- and adult-directed speech are reported for three, genetically
      diverse languages. Previous research has suggested that the prosodic
      characteristics of infant-directed speech are slowed speech rate, raised mean
      pitch, and expanded pitch range relative to adult-directed speech. Sixteen
      mothers (5 Sri Lankan Tamil, 5 Tagalog, 6 Korean) were recorded in their homes
      during natural interactions with their young infants, and adults, over the course
      of 12 months beginning when the infant was 4 months old. Regression models
      indicated that the difference between infant- and adult-directed speech rates
      decreased across the first year of infants' development. Models of pitch revealed
      predicted differences between infant- and adult-directed speech but did not
      provide evidence for cross-linguistic or longitudinal effects within the time
      period investigated for the three languages. The universality of slowed speech
      rate, raised pitch, and expanded pitch range is discussed in light of
      individuals' highly variable implementation of these prosodic features in infant
      directed speech. 

PMID- 27036264
TI  - On band gap predictions for multiresonant metamaterials on plates.
AB  - Recently wide frequency band gaps were observed in an experimental realization of
      a multiresonant metamaterial for Lamb waves propagating in thin plates. The band
      gaps rose from hybridization between the flexural plate (A0 Lamb waves) and
      longitudinal resonances in rods attached perpendicularly. Shortly thereafter a
      theory based on considering a one-dimensional periodic array of rods and the
      scattering matrix for a single rod successfully described the observations. This
      letter presents an alternative simpler theory, arguably accurate at high rod
      density, that treats the full two-dimensional array of rods and makes no
      assumption of periodicity. This theory also fits the measurements. 

PMID- 27036265
TI  - Vocalizations of Amazon river dolphins (Inia geoffrensis): Characterization,
      effect of physical environment and differences between populations.
AB  - The vocal repertoire of the Amazon river dolphin and its geographic variations
      are still poorly known, especially in relation to ecological variables. Here the
      acoustic characteristics of low frequency pulsed vocalizations, with single or
      multiple pulses, recorded in two protected areas of the Amazon were described and
      differences in acoustic emissions related to water properties were analyzed. Both
      frequency and time parameters differ relative to abiotic condition of water
      turbidity. Changes in the animals' acoustic behavior might be due to differences
      in sound propagation between rich-sediment water and clear water. Geographic
      variation was found in frequency and time parameters, requiring further
      investigation. 

PMID- 27036266
TI  - Generation of half-space sound fields with application to personal sound systems.
AB  - A method is presented for generating a sound field that is significantly
      attenuated over half of the reproduction region, which has application to the
      generation of two independent sound fields for two listeners. The half-space
      sound field is produced by attenuating the negative or positive modes in the
      cylindrical or spherical expansion of a plane wave or point source sound field.
      It is shown that this is equivalent to adding to the original sound field, in
      quadrature, a second field which is the Hilbert transform of the original field.
      The resulting analytic field has a small magnitude in one half of the plane.
      Methods are presented for controlling the attenuation in the unwanted half-space.
      Finally, a simulation is presented showing the generation of a wideband pulse
      that propagates across half of the area within a circular array of sources. 

PMID- 27036267
TI  - Auditory masking of speech in reverberant multi-talker environments.
AB  - Auditory localization research needs to be performed in more realistic testing
      environments to better capture the real-world abilities of listeners and their
      hearing devices. However, there are significant challenges involved in
      controlling the audibility of relevant target signals in realistic environments.
      To understand the important aspects influencing target detection in more complex
      environments, a reverberant room with a multi-talker background was simulated and
      presented to the listener in a loudspeaker-based virtual sound environment.
      Masked thresholds of a short speech stimulus were measured adaptively for
      multiple target source locations in this scenario. It was found that both
      distance and azimuth of the target source have a strong influence on the masked
      threshold. Subsequently, a functional model was applied to analyze the factors
      influencing target detectability. The model is comprised of an auditory front-end
      that generates an internal representation of the stimuli in both ears, followed
      by a decision device combining d' information across time, frequency and both
      ears. The model predictions of the masked thresholds were overall in very good
      agreement with the experimental results. An analysis of the model processes
      showed that head shadow effects, signal spectrum, and reverberation have a strong
      impact on target audibility in the given scenario. 

PMID- 27036269
TI  - Robust spot-poled membrane hydrophones for measurement of large amplitude
      pressure waveforms generated by high intensity therapeutic ultrasonic
      transducers.
AB  - The output characterization of medical high intensity therapeutic ultrasonic
      devices poses several challenges for the hydrophones to be used for pressure
      measurements. For measurements at clinical levels in the focal region, extreme
      robustness, broad bandwidth, large dynamic range, and small receiving element
      size are all needed. Conventional spot-poled membrane hydrophones, in principle,
      meet some of these features and were used to detect large amplitude ultrasonic
      fields to investigate their applicability. Cavitation in water was the limiting
      effect causing damage to the electrodes and membrane. A new hydrophone design
      comprising a steel foil front protection layer has been developed, manufactured,
      characterized, tested, and optimized. The latest prototypes additionally
      incorporate a low absorption and acoustic impedance matched backing, and could be
      used for maximum peak rarefactional and peak compressional pressure measurements
      of 15 and 75 MPa, respectively, at 1.06 MHz driving frequency. Axial and lateral
      beam profiles were measured also for a higher driving frequency of 3.32 MHz to
      demonstrate the applicability for output beam characterization at the focal
      region at clinical levels. The experimental results were compared with results of
      numerical nonlinear sound field simulations and good agreement was found if
      detection bandwidth and spatial averaging were taken into account.

PMID- 27036270
TI  - How deaf are French speakers to stress?
AB  - This event-related potential study examined whether French listeners use stress
      at a phonological level when discriminating between stressed and unstressed words
      in their language. Participants heard five words and made same/different
      decisions about the final word (male voice) with respect to the four preceding
      words (different female voices). Compared to the first four context words, the
      target word was (i) phonemically and prosodically identical (/?u/-/?u/; control
      condition), (ii) phonemically identical but differing in the presence of a
      primary stress (/?u'/-/?u/), (iii) prosodically identical but phonemically
      different (/?o/-/?u/), or (iv) both phonemically and prosodically different
      (/?o'/-/?u/). Crucially, differences on the P200 and the following N200
      components were observed for the /?u'/-/?u/ and the /?o/-/?u/ conditions compared
      to the /?u/-/?u/ control condition. Moreover, on the N200 component more
      negativity was observed for the /?o/-/?u/ condition compared to the /?u'/-/?u/
      conditions, while no difference emerged between these two conditions on the
      earlier P200 component. Crucially, the results suggest that French listeners are
      capable of creating an abstract representation of stress. However, as they
      receive more input, participants react more strongly to phonemic than to stress
      information. 

PMID- 27036271
TI  - An explicit analytical solution for sound propagation in a three-dimensional
      penetrable wedge with small apex angle.
AB  - A problem of sound propagation in a shallow-water waveguide with a weakly sloping
      penetrable bottom is considered. The adiabatic mode parabolic equations are used
      to approximate the solution of the three-dimensional (3D) Helmholtz equation by
      modal decomposition of the acoustic pressure field. The mode amplitudes satisfy
      parabolic equations that admit analytical solutions in the special case of the 3D
      wedge. Using the analytical formula for modal amplitudes, an explicit and
      remarkably simple expression for the acoustic pressure in the wedge is obtained.
      The proposed solution is validated by the comparison with a solution of the 3D
      penetrable wedge problem obtained using a fully 3D parabolic equation that
      includes a leading-order cross term correction. 

PMID- 27036272
TI  - Experimental quantification of the true efficiency of carbon nanotube thin-film
      thermophones.
AB  - Carbon nanotube thermophones can create acoustic waves from 1 Hz to 100 kHz. The
      thermoacoustic effect that allows for this non-vibrating sound source is
      naturally inefficient. Prior efforts have not explored their true efficiency
      (i.e., the ratio of the total acoustic power to the electrical input power). All
      previous works have used the ratio of sound pressure to input electrical power. A
      method for true power efficiency measurement is shown using a fully anechoic
      technique. True efficiency data are presented for three different drive signal
      processing techniques: standard alternating current (AC), direct current added to
      alternating current (DCAC), and amplitude modulation of an alternating current
      (AMAC) signal. These signal processing techniques are needed to limit the
      frequency doubling non-linear effects inherent to carbon nanotube thermophones.
      Each type of processing affects the true efficiency differently. Using a 72
      W(rms) input signal, the measured efficiency ranges were 4.3 * 10(-6) - 319 * 10(
      6), 1.7 * 10(-6) - 308 * 10(-6), and 1.2 * 10(-6) - 228 * 10(-6)% for AC, DCAC,
      and AMAC, respectively. These data were measured in the frequency range of 100 Hz
      to 10 kHz. In addition, the effects of these processing techniques relative to
      sound quality are presented in terms of total harmonic distortion.

PMID- 27036274
TI  - Acoustic centering of a baffled piston in the circular harmonics domain.
AB  - The acoustic center of radiating sources is relevant to the modeling of radiation
      patterns and to their effective implementation in acoustical applications and
      computer models. However, the acoustic center of the sources may not be unique
      and therefore should be defined. Previously studied source centering algorithms
      used analytic methods for specific acoustic models, or applied post processing
      methods on a recorded sound from an acoustic source that was surrounded by a
      spherical microphone array. This work performs an acoustic centering of a
      radiating circular baffled piston that is formed by an open termination of a
      circular pipe. A signal processing based acoustic centering algorithm is
      redefined for this case and is shown to be correlated with the effective length
      of the pipe. 

PMID- 27036273
TI  - Autophonic loudness perception in Parkinson's disease.
AB  - The relationship between the intensity and loudness of self-generated
      (autophonic) speech remains invariant despite changes in auditory feedback,
      indicating that non-auditory processes contribute to this form of perception. The
      aim of the current study was to determine if the speech perception deficit
      associated with Parkinson's disease may be linked to deficits in such processes.
      Loudness magnitude estimates were obtained from parkinsonian and non-parkinsonian
      subjects across four separate conditions: self-produced speech under normal,
      perturbed, and masked auditory feedback, as well as auditory presentation of pre
      recorded speech (passive listening). Slopes and intercepts of loudness curves
      were compared across groups and conditions. A significant difference in slope was
      found between autophonic and passive-listening conditions for both groups. Unlike
      control subjects, parkinsonian subjects' magnitude estimates under auditory
      masking increased in variability and did not show as strong a shift in intercept
      values. These results suggest that individuals with Parkinson's disease rely on
      auditory feedback to compensate for underlying deficits in sensorimotor
      integration important in establishing and regulating autophonic loudness. 

PMID- 27036275
TI  - Dynamics of biosonar signals in free-swimming and stationary dolphins: The role
      of source levels on the characteristics of the signals.
AB  - The biosonar signals of two free-swimming Atlantic bottlenose dolphins performing
      a complex sonar search for a bottom target in San Diego Bay were compared with
      the biosonar signals of a dolphin performing a target discrimination task in a
      net pen in the same bay. A bite-plate device carried by the free-swimming
      dolphins supported a hydrophone that extended directly in front of the dolphin. A
      biosonar measuring tool attached to the bite plate measured the outgoing biosonar
      signals while the dolphins conducted sonar searches. Each of the free-swimming
      dolphins used different biosonar search strategy in solving the problem and the
      dolphins' biosonar signals reflect the difference in strategy. The dolphin in the
      pen stationed in a hoop while echolocating on a target 6 m away and reported if
      the indentation on a spherical target was directed toward it. The signals were
      parameterized by determining the peak-to-peak source levels, source energy flux
      density, peak frequency, center frequency, root-mean-square (rms) bandwidth, rms
      duration, and the Q of the signals. Some parameters were similar for the free
      swimming and stationary dolphins while some were significantly different,
      suggesting biosonar signals used by free-swimming animals may be different than
      signals used by dolphins in a pen.

PMID- 27036276
TI  - Evolution of the derivative skewness for nonlinearly propagating waves.
AB  - The skewness of the first time derivative of a pressure waveform, or derivative
      skewness, has been used previously to describe the presence of shock-like content
      in jet and rocket noise. Despite its use, a quantitative understanding of
      derivative skewness values has been lacking. In this paper, the derivative
      skewness for nonlinearly propagating waves is investigated using analytical,
      numerical, and experimental methods. Analytical expressions for the derivative
      skewness of an initially sinusoidal plane wave are developed and, along with
      numerical data, are used to describe its behavior in the preshock, sawtooth, and
      old-age regions. Analyses of common measurement issues show that the derivative
      skewness is relatively sensitive to the effects of a smaller sampling rate, but
      less sensitive to the presence of additive noise. In addition, the derivative
      skewness of nonlinearly propagating noise is found to reach greater values over a
      shorter length scale relative to sinusoidal signals. A minimum sampling rate is
      recommended for sinusoidal signals to accurately estimate derivative skewness
      values up to five, which serves as an approximate threshold indicating
      significant shock formation. 

PMID- 27036277
TI  - Modeling the voice source in terms of spectral slopes.
AB  - A psychoacoustic model of the voice source spectrum is proposed. The model is
      characterized by four spectral slope parameters: the difference in amplitude
      between the first two harmonics (H1-H2), the second and fourth harmonics (H2-H4),
      the fourth harmonic and the harmonic nearest 2 kHz in frequency (H4-2 kHz), and
      the harmonic nearest 2 kHz and that nearest 5 kHz (2 kHz-5 kHz). As a step toward
      model validation, experiments were conducted to establish the acoustic and
      perceptual independence of these parameters. In experiment 1, the model was fit
      to a large number of voice sources. Results showed that parameters are
      predictable from one another, but that these relationships are due to overall
      spectral roll-off. Two additional experiments addressed the perceptual
      independence of the source parameters. Listener sensitivity to H1-H2, H2-H4, and
      H4-2 kHz did not change as a function of the slope of an adjacent component,
      suggesting that sensitivity to these components is robust. Listener sensitivity
      to changes in spectral slope from 2 kHz to 5 kHz depended on complex interactions
      between spectral slope, spectral noise levels, and H4-2 kHz. It is concluded that
      the four parameters represent non-redundant acoustic and perceptual aspects of
      voice quality.

PMID- 27036278
TI  - Active control and sound synthesis--two different ways to investigate the
      influence of the modal parameters of a guitar on its sound.
AB  - The vibrational behavior of musical instruments is usually studied using physical
      modeling and simulations. Recently, active control has proven its efficiency to
      experimentally modify the dynamical behavior of musical instruments. This
      approach could also be used as an experimental tool to systematically study fine
      physical phenomena. This paper proposes to use modal active control as an
      alternative to sound simulation to study the complex case of the coupling between
      classical guitar strings and soundboard. A comparison between modal active
      control and sound simulation investigates the advantages, the drawbacks, and the
      limits of these two approaches. 

PMID- 27036279
TI  - Nonlinear acoustic pulse propagation in dispersive sediments using fractional
      loss operators.
AB  - The nonlinear progressive wave equation (NPE) is a time-domain formulation of the
      Euler fluid equations designed to model low-angle wave propagation using a wave
      following computational domain. The wave-following frame of reference permits the
      simulation of long-range propagation and is useful in modeling blast wave effects
      in the ocean waveguide. Existing models do not take into account frequency
      dependent sediment attenuation, a feature necessary for accurately describing
      sound propagation over, into, and out of the ocean sediment. Sediment attenuation
      is addressed in this work by applying lossy operators to the governing equation
      that are based on a fractional Laplacian. These operators accurately describe
      frequency-dependent attenuation and dispersion in typical ocean sediments.
      However, dispersion within the sediment is found to be a secondary process to
      absorption and effectively negligible for ranges of interest. The resulting
      fractional NPE is benchmarked against a Fourier-transformed parabolic equation
      solution for a linear case, and against the analytical Mendousse solution to
      Burgers' equation for the nonlinear case. The fractional NPE is then used to
      investigate the effects of attenuation on shock wave propagation. 

PMID- 27036280
TI  - Introductory remarks for special issue on wind turbine noise.

PMID- 27036281
TI  - Wind turbine sound power measurements.
AB  - This paper provides experimental validation of the sound power level data
      obtained from manufacturers for the ten wind turbine models examined in Health
      Canada's Community Noise and Health Study (CNHS). Within measurement uncertainty,
      the wind turbine sound power levels measured using IEC 61400-11 [(2002).
      (International Electrotechnical Commission, Geneva)] were consistent with the
      sound power level data provided by manufacturers. Based on measurements, the
      sound power level data were also extended to 16 Hz for calculation of C-weighted
      levels. The C-weighted levels were 11.5 dB higher than the A-weighted levels
      (standard deviation 1.7 dB). The simple relationship between A- and C- weighted
      levels suggests that there is unlikely to be any statistically significant
      difference between analysis based on either C- or A-weighted data. 

PMID- 27036282
TI  - Wind turbine sound pressure level calculations at dwellings.
AB  - This paper provides calculations of outdoor sound pressure levels (SPLs) at
      dwellings for 10 wind turbine models, to support Health Canada's Community Noise
      and Health Study. Manufacturer supplied and measured wind turbine sound power
      levels were used to calculate outdoor SPL at 1238 dwellings using ISO [(1996).
      ISO 9613-2-Acoustics] and a Swedish noise propagation method. Both methods
      yielded statistically equivalent results. The A- and C-weighted results were
      highly correlated over the 1238 dwellings (Pearson's linear correlation
      coefficient r > 0.8). Calculated wind turbine SPLs were compared to ambient SPLs
      from other sources, estimated using guidance documents from the United States and
      Alberta, Canada. 

PMID- 27036283
TI  - Exposure to wind turbine noise: Perceptual responses and reported health effects.
AB  - Health Canada, in collaboration with Statistics Canada, and other external
      experts, conducted the Community Noise and Health Study to better understand the
      impacts of wind turbine noise (WTN) on health and well-being. A cross-sectional
      epidemiological study was carried out between May and September 2013 in
      southwestern Ontario and Prince Edward Island on 1238 randomly selected
      participants (606 males, 632 females) aged 18-79 years, living between 0.25 and
      11.22 km from operational wind turbines. Calculated outdoor WTN levels at the
      dwelling reached 46 dBA. Response rate was 78.9% and did not significantly differ
      across sample strata. Self-reported health effects (e.g., migraines, tinnitus,
      dizziness, etc.), sleep disturbance, sleep disorders, quality of life, and
      perceived stress were not related to WTN levels. Visual and auditory perception
      of wind turbines as reported by respondents increased significantly with
      increasing WTN levels as did high annoyance toward several wind turbine features,
      including the following: noise, blinking lights, shadow flicker, visual impacts,
      and vibrations. Concern for physical safety and closing bedroom windows to reduce
      WTN during sleep also increased with increasing WTN levels. Other sample
      characteristics are discussed in relation to WTN levels. Beyond annoyance,
      results do not support an association between exposure to WTN up to 46 dBA and
      the evaluated health-related endpoints. 

PMID- 27036284
TI  - Personal and situational variables associated with wind turbine noise annoyance.
AB  - The possibility that wind turbine noise (WTN) affects human health remains
      controversial. The current analysis presents results related to WTN annoyance
      reported by randomly selected participants (606 males, 632 females), aged 18-79,
      living between 0.25 and 11.22 km from wind turbines. WTN levels reached 46 dB,
      and for each 5 dB increase in WTN levels, the odds of reporting to be either very
      or extremely (i.e., highly) annoyed increased by 2.60 [95% confidence interval:
      (1.92, 3.58), p < 0.0001]. Multiple regression models had R(2)'s up to 58%, with
      approximately 9% attributed to WTN level. Variables associated with WTN annoyance
      included, but were not limited to, other wind turbine-related annoyances,
      personal benefit, noise sensitivity, physical safety concerns, property
      ownership, and province. Annoyance was related to several reported measures of
      health and well-being, although these associations were statistically weak (R(2
      )< 9%), independent of WTN levels, and not retained in multiple regression
      models. The role of community tolerance level as a complement and/or an
      alternative to multiple regression in predicting the prevalence of WTN annoyance
      is also provided. The analysis suggests that communities are between 11 and 26 dB
      less tolerant of WTN than of other transportation noise sources.

PMID- 27036285
TI  - Self-reported and measured stress related responses associated with exposure to
      wind turbine noise.
AB  - The current study was the first to assess stress reactions associated with wind
      turbine noise (WTN) exposure using self-reported and objective measures. Randomly
      selected participants, aged 18-79 yr (606 males; 632 females), living between
      0.25 and 11.22 km from wind turbines, were exposed to outdoor calculated WTN
      levels up to 46 dBA (response rate 78.9%). Multiple regression modeling left the
      great majority (77%-89%) of the variance in perceived stress scale (PSS) scores,
      hair cortisol concentrations, resting blood pressure, and heart rate unaccounted
      for, and WTN exposure had no apparent influence on any of these endpoints. PSS
      scores were positively, but weakly, related to cortisol concentrations and
      resting heart rate (Pearson r = 0.13 and r = 0.08, respectively). Across WTN
      categories, modeled mean PSS scores ranged from 13.15 to 13.84 (p = 0.8614).
      Modeled geometric means for hair cortisol concentrations, resting mean systolic,
      diastolic blood pressure, and heart rate were 150.54-191.12 ng/g (p = 0.5416),
      113.38-116.82 mmHg (p = 0.4990), 67.98-70.34 mmHg (p = 0.5006), and 68.24-70.71
      bpm (p = 0.5223), respectively. Irrespective of WTN levels, diastolic blood
      pressure appeared to be slightly (2.90 mmHg 95% CI: 0.75,5.05) higher among
      participants highly annoyed by blinking lights on turbines (p = 0.0081).
      Collectively, the findings do not support an association between exposure to WTN
      up to 46 dBA and elevated self-reported and objectively defined measures of
      stress.

PMID- 27036286
TI  - Estimating annoyance to calculated wind turbine shadow flicker is improved when
      variables associated with wind turbine noise exposure are considered.
AB  - The Community Noise and Health Study conducted by Health Canada included randomly
      selected participants aged 18-79 yrs (606 males, 632 females, response rate
      78.9%), living between 0.25 and 11.22 km from operational wind turbines.
      Annoyance to wind turbine noise (WTN) and other features, including shadow
      flicker (SF) was assessed. The current analysis reports on the degree to which
      estimating high annoyance to wind turbine shadow flicker (HAWTSF) was improved
      when variables known to be related to WTN exposure were also considered. As SF
      exposure increased [calculated as maximum minutes per day (SFm)], HAWTSF
      increased from 3.8% at 0 <= SFm < 10 to 21.1% at SFm >= 30, p < 0.0001. For each
      unit increase in SFm the odds ratio was 2.02 [95% confidence interval:
      (1.68,2.43)]. Stepwise regression models for HAWTSF had a predictive strength of
      up to 53% with 10% attributed to SFm. Variables associated with HAWTSF included,
      but were not limited to, annoyance to other wind turbine-related features,
      concern for physical safety, and noise sensitivity. Reported dizziness was also
      retained in the final model at p = 0.0581. Study findings add to the growing
      science base in this area and may be helpful in identifying factors associated
      with community reactions to SF exposure from wind turbines.

PMID- 27036287
TI  - Musician advantage for speech-on-speech perception.
AB  - Evidence for transfer of musical training to better perception of speech in noise
      has been mixed. Unlike speech-in-noise, speech-on-speech perception utilizes many
      of the skills that musical training improves, such as better pitch perception and
      stream segregation, as well as use of higher-level auditory cognitive functions,
      such as attention. Indeed, despite the few non-musicians who performed as well as
      musicians, on a group level, there was a strong musician benefit for speech
      perception in a speech masker. This benefit does not seem to result from better
      voice processing and could instead be related to better stream segregation or
      enhanced cognitive functions. 

PMID- 27036288
TI  - Temporal alignment of pupillary response with stimulus events via deconvolution.
AB  - Analysis of pupil dilation has been used as an index of attentional effort in the
      auditory domain. Previous work has modeled the pupillary response to attentional
      effort as a linear time-invariant system with a characteristic impulse response,
      and used deconvolution to estimate the attentional effort that gives rise to
      changes in pupil size. Here it is argued that one parameter of the impulse
      response (the latency of response maximum, t(max)) has been mis-estimated in the
      literature; a different estimate is presented, and it is shown how deconvolution
      with this value of t(max) yields more intuitively plausible and informative
      results.

PMID- 27036289
TI  - A theoretical model of barriers having inhomogeneous impedance surfaces.
AB  - When barriers are placed in parallel on opposite sides of a source, their
      performance deteriorates markedly. However, barriers made from materials of
      inhomogeneous impedance eliminate this drawback by altering the behavior of sound
      as it undergoes multiple reflections between the barriers. In this paper, a
      theoretical approach is carried out to estimate the performance of the proposed
      barriers. By combining the ray-tracing method and sound diffraction theory, the
      existence of different ray paths between the proposed barriers is revealed.
      Compared to conventional rigid-walled barriers, barriers having inhomogeneous
      surfaces may have the potential to be widely used in environmental noise control.

PMID- 27036290
TI  - Evaluating multipulse integration as a neural-health correlate in human cochlear
      implant users: Relationship to forward-masking recovery.
AB  - The present study evaluated the slopes of threshold-versus-pulse-rate functions
      (multipulse integration, MPI) in humans with cochlear implants in relation to
      recovery from 300-ms forward maskers. MPI has been correlated with spiral
      ganglion cell density in animals. The present study showed that steeper MPI
      functions were correlated with faster recovery from forward masking. The findings
      suggested that the variations in the MPI slopes are explained not only by the
      quantity of neurons contributing to the integration process but also by the
      neurons' temporal response characteristics and possibly central inhibition. 

PMID- 27036291
TI  - Effects of L1 prosody on segmental contrast in L2: The case of English stop
      voicing contrast produced by Korean speakers.
AB  - This study investigated how the L1 phonetics-prosody interface transfers to L2 by
      examining prosodic strengthening effects (due to prosodic position and focus) on
      English voicing contrast (bad-pad) as produced by Korean vs English speakers.
      Under prosodic strengthening, Korean speakers showed a greater F0 difference due
      to voicing than English speakers, suggesting that their experience with the
      macroprosodic use of F0 in Korean transfers into L2. Furthermore, Korean speakers
      produced voiced stops with low F0 and short voice onset time as English speakers
      did, although such a cue pairing is absent in Korean, showing dissociation of
      cues from L1 segments for L2 production. 

PMID- 27036292
TI  - Software for real-time localization of baleen whale calls using directional
      sonobuoys: A case study on Antarctic blue whales.
AB  - Directional frequency analysis and recording (DIFAR) sonobuoys can allow real
      time acoustic localization of baleen whales for underwater tracking and remote
      sensing, but limited availability of hardware and software has prevented wider
      usage. These software limitations were addressed by developing a module in the
      open-source software PAMGuard. A case study is presented demonstrating that this
      software provides greater efficiency and accessibility than previous methods for
      detecting, localizing, and tracking Antarctic blue whales in real time.
      Additionally, this software can easily be extended to track other low and mid
      frequency sounds including those from other cetaceans, pinnipeds, icebergs,
      shipping, and seismic airguns. 

PMID- 27036293
TI  - Compressive acoustic sound speed profile estimation.
AB  - Ocean acoustic sound speed profile (SSP) estimation requires the inversion of
      acoustic fields using limited observations. Compressive sensing (CS) asserts that
      certain underdetermined problems can be solved in high resolution, provided their
      solutions are sparse. Here, CS is used to estimate SSPs in a range-independent
      shallow ocean by inverting a non-linear acoustic propagation model. It is shown
      that SSPs can be estimated using CS to resolve fine-scale structure. 

PMID- 27036294
TI  - Erratum to: B cell sub-types following acute malaria and associations with
      clinical immunity.

PMID- 27036295
TI  - IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured
      cells derived from FMDV-susceptible and -insusceptible animals.
AB  - BACKGROUND: Foot-and-mouth disease virus (FMDV) possess a positive sense, single
      stranded RNA genome. Internal ribosomal entry site (IRES) element exists within
      its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA
      is initiated by internal entry of the 40S ribosome within the IRES element. This
      process is facilitated by cellular factors known as IRES trans-acting factors
      (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven
      hoofed animals such as cattle and pigs, but the factors determining the host
      range have not been identified yet. Although, ITAFs are known to promote IRES
      mediated translation, these findings were confirmed only in cells derived from
      FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated
      translation activities among cell lines derived from four different animal
      species using bicistronic luciferase reporter plasmid, which possesses an FMDV
      IRES element between Renilla and Firefly luciferase genes. Furthermore, we
      analyzed the effect of the cellular factors on IRES-mediated translation by
      silencing the cellular factors using siRNA in both FMDV-susceptible and 
      insusceptible animal cells. RESULTS: Our data indicated that IRES-mediated
      translational activity was not linked to FMDV host range. ITAF45 promoted IRES
      mediated translation in all cell lines, and the effects of poly-pyrimidine tract
      binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E
      BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may
      influence the host range of FMDV. CONCLUSIONS: IRES-mediated translation activity
      of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated
      translation in all cells, and the effects of PTB and 4E-BP1 were observed only in
      FMDV-susceptible cells.

PMID- 27036296
TI  - The effects of maximising the UK's tobacco control score on inequalities in
      smoking prevalence and premature coronary heart disease mortality: a modelling
      study.
AB  - BACKGROUND: Smoking is more than twice as common among the most disadvantaged
      socioeconomic groups in England compared to the most affluent and is a major
      contributor to health-related inequalities. The United Kingdom (UK) has
      comprehensive smoking policies in place: regular tax increases; public
      information campaigns; on-pack pictorial health warnings; advertising bans;
      cessation; and smoke-free areas. This is confirmed from its high Tobacco Control
      Scale (TCS) score, an expert-developed instrument for assessing the strength of
      tobacco control policies. However, room remains for improvement in tobacco
      control policies. Our aim was to evaluate the cumulative effect on smoking
      prevalence of improving all TCS components in England, stratified by
      socioeconomic circumstance. METHODS: Effect sizes and socioeconomic gradients for
      all six types of smoking policy in the UK setting were adapted from systematic
      reviews, or if not available, from primary studies. We used the IMPACT Policy
      Model to link predicted changes in smoking prevalence to changes in premature
      coronary heart disease (CHD) mortality for ages 35-74. Health outcomes with a
      time horizon of 2025 were stratified by quintiles of socioeconomic circumstance.
      RESULTS: The model estimated that improving all smoking policies to achieve a
      maximum score on the TCS might reduce smoking prevalence in England by 3% (95%
      Confidence Interval (CI): 1-4%), from 20 to 17% in absolute terms, or by 15% in
      relative terms (95% CI: 7-21%). The most deprived quintile would benefit more,
      with absolute reductions from 31 to 25%, or a 6% reduction (95% CI: 2-7%). There
      would be some 3300 (95% CI: 2200-4700) fewer premature CHD deaths between 2015
      2025, a 2% (95% CI: 1.4-2.9%) reduction. The most disadvantaged quintile would
      benefit more, reducing absolute inequality of CHD mortality by about 4 % (95% CI:
      3-9%). CONCLUSIONS: Further, feasible improvements in tobacco control policy
      could substantially improve population health, and reduce health-related
      inequalities in England.

PMID- 27036297
TI  - Naringenin prevents TGF-beta1 secretion from breast cancer and suppresses
      pulmonary metastasis by inhibiting PKC activation.
AB  - BACKGROUND: Targeting the TGF-beta1 pathway for breast cancer metastasis therapy
      has become an attractive strategy. We have previously demonstrated that
      naringenin significantly reduced TGF-beta1 levels in bleomycin-induced lung
      fibrosis and effectively prevented pulmonary metastases of tumors. This raised
      the question of whether naringenin can block TGF-beta1 secretion from breast
      cancer cells and inhibit their pulmonary metastasis. METHODS: We transduced a
      lentiviral vector encoding the mouse Tgf-beta1 gene into mouse breast carcinoma
      (4T1-Luc2) cells and inoculated the transformant cells (4T1/TGF-beta1) into the
      fourth primary fat pat of Balb/c mice. Pulmonary metastases derived from the
      primary tumors were monitored using bioluminescent imaging. Spleens, lungs and
      serum (n = 18-20 per treatment group) were analyzed for immune cell activity and
      TGF-beta1 level. The mechanism whereby naringenin decreases TGF-beta1 secretion
      from breast cancer cells was investigated at different levels, including Tgf
      beta1 transcription, mRNA stability, translation, and extracellular release.
      RESULTS: In contrast to the null-vector control (4T1/RFP) tumors, extensive
      pulmonary metastases derived from 4T1/TGF-beta1 tumors were observed.
      Administration of the TGF-beta1 blocking antibody 1D11 or naringenin showed an
      inhibition of pulmonary metastasis for both 4T1/TGF-beta1 tumors and 4T1/RFP
      tumors, resulting in increased survival of the mice. Compared with 4T1/RFP
      bearing mice, systemic immunosuppression in 4T1/TGF-beta1 bearing mice was
      observed, represented by a higher proportion of regulatory T cells and myeloid
      derived suppressor cells and a lower proportion of activated T cells and INFgamma
      expression in CD8(+) T cells. These metrics were improved by administration of
      1D11 or naringenin. However, compared with 1D11, which neutralized secreted TGF
      beta1 but did not affect intracellular TGF-beta1 levels, naringenin reduced the
      secretion of TGF-beta1 from the cells, leading to an accumulation of
      intracellular TGF-beta1. Further experiments revealed that naringenin had no
      effect on Tgf-beta1 transcription, mRNA decay or protein translation, but
      prevented TGF-beta1 transport from the trans-Golgi network by inhibiting PKC
      activity. CONCLUSIONS: Naringenin blocks TGF-beta1 trafficking from the trans
      Golgi network by suppressing PKC activity, resulting in a reduction of TGF-beta1
      secretion from breast cancer cells. This finding suggests that naringenin may be
      an attractive therapeutic candidate for TGF-beta1 related diseases.

PMID- 27036298
TI  - De novo genome assembly and annotation of rice sheath rot fungus Sarocladium
      oryzae reveals genes involved in Helvolic acid and Cerulenin biosynthesis
      pathways.
AB  - BACKGROUND: Sheath rot disease caused by Sarocladium oryzae is an emerging threat
      for rice cultivation at global level. However, limited information with respect
      to genomic resources and pathogenesis is a major setback to develop disease
      management strategies. Considering this fact, we sequenced the whole genome of
      highly virulent Sarocladium oryzae field isolate, Saro-13 with 82x sequence
      depth. RESULTS: The genome size of S. oryzae was 32.78 Mb with contig N50 18.07
      Kb and 10526 protein coding genes. The functional annotation of protein coding
      genes revealed that S. oryzae genome has evolved with many expanded gene families
      of major super family, proteinases, zinc finger proteins, sugar transporters,
      dehydrogenases/reductases, cytochrome P450, WD domain G-beta repeat and FAD
      binding proteins. Gene orthology analysis showed that around 79.80 % of S. oryzae
      genes were orthologous to other Ascomycetes fungi. The polyketide synthase
      dehydratase, ATP-binding cassette (ABC) transporters, amine oxidases, and
      aldehyde dehydrogenase family proteins were duplicated in larger proportion
      specifying the adaptive gene duplications to varying environmental conditions.
      Thirty-nine secondary metabolite gene clusters encoded for polyketide synthases,
      nonribosomal peptide synthase, and terpene cyclases. Protein homology based
      analysis indicated that nine putative candidate genes were found to be involved
      in helvolic acid biosynthesis pathway. The genes were arranged in cluster and
      structural organization of gene cluster was similar to helvolic acid biosynthesis
      cluster in Metarhizium anisophilae. Around 9.37 % of S. oryzae genes were
      identified as pathogenicity genes, which are experimentally proven in other
      phytopathogenic fungi and enlisted in pathogen-host interaction database. In
      addition, we also report 13212 simple sequences repeats (SSRs) which can be
      deployed in pathogen identification and population dynamic studies in near
      future. CONCLUSIONS: Large set of pathogenicity determinants and putative genes
      involved in helvolic acid and cerulenin biosynthesis will have broader
      implications with respect to Sarocladium disease biology. This is the first
      genome sequencing report globally and the genomic resources developed from this
      study will have wider impact worldwide to understand Rice-Sarocladium
      interaction.

PMID- 27036299
TI  - Endoscopic submucosal dissection for an atypical small verrucous carcinoma: a
      case report.
AB  - BACKGROUND: Esophageal verrucous carcinoma is a rare variant of esophageal
      squamous cell carcinoma. In most cases, verrucous carcinoma presents as an
      exophytic, slow-growing mass with an extensive superficial growth pattern.
      Symptoms often include an insidious onset of dysphagia resulting in weight loss.
      In a patient presenting with super early-stage verrucous carcinoma, we were able
      to eliminate the aberration using endoscopic submucosal dissection. CASE
      PRESENTATION: An asymptomatic 68-year-old Asian man was found to have an
      abnormality in his esophagus. The abnormality was discovered, by chance, in a
      barium study for a health checkup. Esophagogastroduodenoscopy revealed a 1
      centimeter polypoid lesion covered with squamous epithelium. Biopsies showed
      squamous high-grade intraepithelial neoplasia. An endoscopic submucosal
      dissection was performed and the histopathological findings showed a well
      differentiated squamous cell carcinoma with hyperkeratosis with a church spire
      configuration. These features are consistent with the growth pattern of verrucous
      carcinoma. CONCLUSIONS: Verrucous carcinoma can manifest as a small mass with
      nonclinical symptoms and endoscopic submucosal dissection is useful as a curative
      treatment. We must consider that verrucous carcinoma can manifest as appearance
      of a polyp that is not papillary or warty-like with and without extensive
      superficial growth appearance.

PMID- 27036300
TI  - The intensive and extensive margins of contraceptive use: comparing the effects
      of method choice and method initiation.
AB  - OBJECTIVES: The risk of pregnancy is estimated to be 20 times as high among women
      who use oral contraception, and 90 times as high among condom users, as among
      women who use certain long-acting contraceptive methods. We explored the
      population-level implications of this variation in contraceptive efficacy. STUDY
      DESIGN: We used the FamilyScape 3.0 microsimulation model to study the effects on
      the nonmarital pregnancy rate of movements along two different margins of
      contraceptive behavior: the extensive margin, which captures decisions about
      whether to initiate use of any method of contraception among noncontraceptors;
      and the intensive margin, which captures the choice of methods among
      contraceptors. The model is populated with a nationally representative sample of
      50,000 women who are of childbearing age. RESULTS: The impact on the number of
      nonmarital pregnancies would not be substantially different if noncontraceptors
      adopted long-acting methods than if they began using oral contraception.
      Moreover, the nonmarital pregnancy rate would be reduced by about twice as much
      if a subset of noncontraceptors began using condoms as if an equal number of pill
      users took up long-acting methods. CONCLUSIONS: The prevailing emphasis on long
      acting contraception is somewhat misplaced. Policymakers and practitioners will
      have the largest effects on fertility outcomes if they can change the behavior of
      sexually active women who neglect to use birth control when they are not seeking
      pregnancy. IMPLICATIONS: Women's decisions about which methods to use are less
      impactful than their decisions about whether to use contraception at all. The
      policies that affect method choice are likely to differ from the policies that
      address the underlying motivations of noncontraceptors who are not seeking
      pregnancy.

PMID- 27036301
TI  - The Research Consortium on Religious Healthcare Institutions: studying the impact
      of religious restrictions on women's reproductive health.
AB  - Catholic hospitals and other religious institutions are a large and growing part
      of the US health care system. They have specific policies restricting
      reproductive health care. Despite increased public attention in the media to
      women denied necessary pregnancy-related care at Catholic hospitals, research on
      the effects of religious restrictions remains limited. This article summarizes
      research priorities as generated by 80 attendees at the inaugural meeting of the
      Research Consortium on Religious Healthcare Institutions. Such research is need
      to understand the impact of religious health system ownership on women's health.

PMID- 27036302
TI  - A frameshift mutation in GON4L is associated with proportionate dwarfism in
      Fleckvieh cattle.
AB  - BACKGROUND: Low birth weight and postnatal growth restriction are the most
      evident symptoms of dwarfism. Accompanying skeletal aberrations may compromise
      the general condition and locomotion of affected individuals. Several paternal
      half-sibs with a low birth weight and a small size were born in 2013 in the
      Fleckvieh cattle population. RESULTS: Affected calves were strikingly underweight
      at birth in spite of a normal gestation length and had craniofacial abnormalities
      such as elongated narrow heads and brachygnathia inferior. In spite of a normal
      general condition, their growth remained restricted during rearing. We genotyped
      27 affected and 10,454 unaffected animals at 44,672 single nucleotide
      polymorphisms and performed association tests followed by homozygosity mapping,
      which allowed us to map the locus responsible for growth failure to a 1.85-Mb
      segment on bovine chromosome 3. Analysis of whole-genome re-sequencing data from
      one affected and 289 unaffected animals revealed a 1-bp deletion (g.15079217delC,
      rs723240647) in the coding region of the GON4L gene that segregated with the
      dwarfism-associated haplotype. We showed that the deletion induces intron
      retention and premature termination of translation, which can lead to a severely
      truncated protein that lacks domains that are likely essential to normal protein
      function. The widespread use of an undetected carrier bull for artificial
      insemination has resulted in a tenfold increase in the frequency of the
      deleterious allele in the female population. CONCLUSIONS: A frameshift mutation
      in GON4L is associated with autosomal recessive proportionate dwarfism in
      Fleckvieh cattle. The mutation has segregated in the population for more than 50
      years without being recognized as a genetic disorder. However, the widespread use
      of an undetected carrier bull for artificial insemination caused a sudden
      accumulation of homozygous calves with dwarfism. Our findings provide the basis
      for genome-based mating strategies to avoid the inadvertent mating of carrier
      animals and thereby prevent the birth of homozygous calves with impaired growth.

PMID- 27036303
TI  - Visceral adiposity is associated with cytokines and decrease in lung function in
      women with persistent asthma.
AB  - Abdominal obesity is associated with a risk of cardiovascular diseases, metabolic
      syndrome and decreased lung function. However, it is not known whether asthma
      control is influenced by the accumulation of adipose tissue in the various
      abdominal compartments. OBJECTIVE: To determine associations among abdominal
      adiposity distribution, asthma control, lung function and cytokines in women.
      METHODS AND DESIGN: In this cross-sectional study of asthmatic women, data on
      demographic variables, comorbid conditions, disease history, anthropometric and
      spirometric measurements were collected. Subcutaneous (SAT) and visceral (VAT)
      adipose tissues were measured by ultrasound, and the steatosis level was
      obtained. Asthma control was assessed according to Global Initiative for Asthma
      (GINA) criteria. Atopy was defined on the basis of allergen-specific
      Immunoglobulin E and/or skin prick testing. Cytokine levels were determined using
      enzyme-linked immunosorbant assays (ELISAs). RESULTS: Eighty-three asthmatic
      women were included, 37% of whom had uncontrolled asthma. After controlling for
      variables, a negative association between asthma control and VAT and the VAT/SAT
      ratio was observed. VAT was negatively associated with respiratory parameters
      after controlling for explanatory variables. In an adjusted model, body mass
      index (BMI) and SAT were inversely associated with the adiponectin serum level
      and VAT was associated with the interleukin 6 level. In conclusion, visceral
      obesity was negatively associated with asthma control and lung function; and
      positively associated with increased levels of interleukin 6 in women. We
      hypothesize that women should be studied as a separate group, and we suggest
      further studies with a control group to know if the uncontrolled asthmatic group
      is directly affected by visceral adipose inflammatory markers.

PMID- 27036304
TI  - The Role of Metastasectomy in Patients with Renal Cell Carcinoma with Sarcomatoid
      Dedifferentiation: A Matched Controlled Analysis.
AB  - PURPOSE: Management of metastatic renal cell carcinoma with sarcomatoid
      dedifferentiation remains a therapeutic challenge with no standard treatment
      strategies. We evaluated whether metastasectomy has any survival benefit in
      patients with metastatic sarcomatoid dedifferentiation treated with radical
      nephrectomy. MATERIALS AND METHODS: From an institutional database of 273
      patients with sarcomatoid dedifferentiation treated with nephrectomy we matched
      80 with synchronous and asynchronous metastases for age, ECOG (Eastern
      Cooperative Oncology Group) performance status, histology and lymph node status.
      Matched pairs were then retained only if patients who did not undergo
      metastasectomy were alive at metastasectomy comparable to matched surgical
      patients to decrease the bias of survival outcomes. Overall survival from
      nephrectomy was studied using univariable and multivariable proportional hazards
      regression. RESULTS: Median overall survival was 8.3 (95% CI 6.5-10.5) and 18.5
      months (95% CI 11.5-42.9) in patients with synchronous and asynchronous
      metastases, respectively. Overall survival in patients who underwent
      metastasectomy for synchronous metastasis compared to nonsurgical patients was
      8.4 and 8.0 months (p = 0.35), respectively. Similarly, overall survival in
      patients with asynchronous metastases treated with metastasectomy compared to the
      nonsurgical group was 36.2 and 13.7 months, respectively (p = 0.29). On
      multivariable analysis positive lymph nodes at nephrectomy were associated with
      an increased risk of death in the synchronous and asynchronous patient subgroups
      (HR 2.1, 95% CI 1.1-4.0, p = 0.03 and HR 3.3, 95% CI 1.2-9.2, p = 0.02,
      respectively). CONCLUSIONS: In the current study there was no clear evidence of
      benefit in patients with sarcomatoid dedifferentiation who underwent
      metastasectomy after nephrectomy. Particularly, the group of patients with
      pathological lymph node positive disease at nephrectomy had considerably worse
      survival.

PMID- 27036305
TI  - Patterns of Care and Survival Outcomes for Malignant Sex Cord Stromal Testicular
      Cancer: Results from the National Cancer Data Base.
AB  - PURPOSE: Sex cord stromal tumors of the testis comprise less than 5% of
      testicular neoplasms. Consequently, data regarding patterns of care and survival
      are sparse. Using a large national database, we sought to provide a more
      definitive analysis of outcomes and management of these malignancies. MATERIALS
      AND METHODS: Data were obtained from the National Cancer Data Base. Patients
      diagnosed from 1998 to 2011 with 2 of the most frequent sex cord stromal tumors
      of the testis, including Leydig and Sertoli cell tumors, were selected for study.
      Overall survival estimates were assessed by the Kaplan-Meier method. RESULTS: Of
      the 79,120 cases of testicular cancer between 1998 and 2011, 315 (0.39%) were
      primary malignant Leydig or Sertoli cell tumors. Median patient age was 43 years
      for both tumors. Of the 315 patients 250 (79%) had malignant Leydig cell tumors
      and 65 (21%) had malignant Sertoli cell tumors, of which 94% and 78%,
      respectively, were stage I. Overall survival at 1 and 5 years for stage I Leydig
      cell tumors was 98% (95% CI 96-100) and 91% (95% CI 85-96), and for stage I
      Sertoli cell tumors overall survival was 93% (95% CI 83-100) and 77% (95% CI 62
      95), respectively (p = 0.015). Of patients with stage I Leydig and Sertoli cell
      tumors 94% and 84%, respectively, received no further treatment following
      orchiectomy. CONCLUSIONS: Five-year survival estimates of stage I Leydig and
      Sertoli cell tumors are significantly lower compared to those of stage I germ
      cell tumors with Sertoli cell tumors significantly worse than Leydig cell tumors.
      These differences in the survival of sex cord stromal tumors indicate the
      importance of large databases to evaluate the efficacy of treatment for rare
      neoplasms.

PMID- 27036307
TI  - [Tutors of resiliency of children and adolescents living in camps in Port-au
      Prince and surrounding cities].
AB  - OBJECTIVES: In the context of sustainable reconstruction of Haiti following the
      earthquake of January 12, 2010, this research analyses the processes of
      resilience and creators of young and adolescent Haitians. In particular, it
      examines the role of family, school, care institutions, beliefs, association
      networks, the state and the international community in the development of these
      processes. These strata are considered as human resources that may assist in the
      living of difficult experiences, and reconstruction-shoring research mainly aims
      to identify guardians' resilience among young and adolescent Haitians living in
      camps in Port-au-Prince and the other most affected cities after the nearby
      earthquake. METHODOLOGY: From a questionnaire developed jointly with the
      University Lumiere Lyon 2 (CRPPC) Editec and the State University of Haiti (UEH)
      in the context of research, individual interviews were conducted with a sample of
      n=1475 children and adolescents, 782 girls and 693 boys, 19% of whom were under
      the age of 6 years, 52% aged 6 to 15 years and 29% aged 15 to 20 years. This
      allowed the collection of their perception and representation of different
      elements, which serve as scaffolding to cope with the post-traumatic situation
      they experienced and to analyse and establish the correlation links between the
      tutors identified. Among the young people in the sample, 97% are mostly educated,
      and they remain in three cities that have been particularly affected by the
      earthquake: the capital Port-au-Prince, Leogane a commune of Port-au-Prince
      located in the department of the West, and Jacmel a commune of Haiti and head of
      the department of the South East. We enjoyed the perception and representation of
      children and adolescents on several potential guardians' resilience: family,
      school, health care institutions, places of worship, social and community
      networks, government and international organizations. RESULTS: Some data
      concluded that tutors can actually be correlated and identified by sex and level
      of development topics. Analyses revealed that the majority of children had not
      lost their parents and said they feel safe with their families. Academic
      performance tended mostly to increase after the earthquake, young people
      perceived care as accessible and available, and the majority claim to be
      Protestant. They certify that they have many friends and have ties in the
      community and feel safe in the streets. The data show a positive dominance of
      religious practice and sense of trust in institutions of care on the part of
      girls while the boys claim to have more confidence in the State. The school
      performance is more important to those aged between 6-15 years, while the older
      ones practice less religion and rely less on the State and international
      organizations. These results suggest the importance of institutions such as the
      family, places of worship, educational institutions, health centres, community,
      etc.

PMID- 27036308
TI  - Proceedings of the Middle East Respiratory Syndrome (MERS) Coronavirus research
      initiative workshop, September 9-10 2015 in Riyadh, KSA.

PMID- 27036310
TI  - Discussion.

PMID- 27036309
TI  - Society for Vascular Surgery limb stage and patient risk correlate with outcomes
      in an amputation prevention program.
AB  - OBJECTIVE: Clinical decision making and accurate outcomes comparisons in advanced
      limb ischemia require improved staging systems. The Society for Vascular Surgery
      Lower Extremity Threatened Limb Classification System (Wound extent, Ischemia,
      and foot Infection [WIfI]) was designed to stratify limb outcomes based on three
      major factors-wound extent, ischemia, and foot infection. The Project or Ex-Vivo
      vein graft Engineering via Transfection III (PREVENT) III (PIII) risk score was
      developed to stratify patients by expected amputation-free survival (AFS) after
      surgical revascularization. This study was designed to prospectively assess limb
      and patient-based staging for predicting outcomes of hospitalized patients in an
      amputation prevention program. METHODS: This study undertook a retrospective
      analysis of prospectively gathered registry data of consecutive patients with
      limb-threatening conditions admitted to a fully integrated vascular/podiatry
      service over a 16-month period. Upon admission, limb risk was stratified using
      the WIfI system and patient risk was categorized using PIII classification.
      Patients were assessed for perioperative and postdischarge outcomes, and their
      relationship to staging at admission was analyzed. RESULTS: There were 174
      threatened limbs (143 hospitalized patients) stratified by WIfI stage (1%-12%, 2%
      28%, 3%-24%, 4%-28%, 5%-3%, unstaged-5%) and PIII risk (34% low, 49% moderate,
      and 17% high risk). Diabetes and end-stage renal disease were associated with
      WIfI stage (P = .006 and P = .018) and PIII risk (P = .003 and P < .001).
      Perioperative (30-day) events included 3% mortality, 8% major adverse
      cardiovascular events and 2.4% major amputation. There were 119 limbs (71%) that
      underwent revascularization, including 108 infrainguinal reconstructions
      (endovascular or open revascularization). Rate of revascularization increased
      with WIfI stage (P < .001), concomitant with the number of podiatric procedures,
      minor amputations, and initial hospital duration of stay (all P < .001).
      Increased WIfI stage was associated with major adverse limb events (P = .018),
      reduced limb salvage (P = .037), and decreased AFS (P = .048). In contrast, PIII
      risk category was associated with mortality (P < .001) and AFS (P < .001). Among
      infrainguinal reconstruction procedures, there was a similar distribution of
      endovascular (46%) and surgical (54%) interventions. Freedom from major adverse
      limb events was best for autogenous vein bypass (P = .025), and surgical
      revascularization was associated with improved limb salvage among the most
      severely threatened limbs (WIfI stage 4: 95% limb salvage for open bypass vs 68%
      limb salvage for endovascular; P = .026). CONCLUSIONS: Among patients
      hospitalized with limb-threatening conditions and treated by a multidisciplinary
      amputation prevention team, PIII risk correlates with mortality whereas WIfI
      stage strongly predicts initial hospital duration of stay, and key mid-term limb
      outcomes. Surgical revascularization performed best in the limbs at greatest risk
      (WIfI stage 4), and autogenous vein bypass was the preferred conduit for open
      bypass. These data support the use of WIfI and PIII as complementary staging
      tools in the management of chronic limb-threatening ischemia.

PMID- 27036311
TI  - Directed differentiation of basal forebrain cholinergic neurons from human
      pluripotent stem cells.
AB  - BACKGROUND: Basal forebrain cholinergic neurons (BFCNs) play critical roles in
      learning, memory and cognition. Dysfunction or degeneration of BFCNs may connect
      to neuropathology, such as Alzheimer's disease, Down's syndrome and dementia.
      Generation of functional BFCNs may contribute to the studies of cell-based
      therapy and pathogenesis that is related to learning and memory deficits. NEW
      METHOD: Here we describe a detail method for robust generation of BFCNs from
      human embryonic stem cells (hESCs) and human induced pluripotent stem cells
      (hiPSCs). In this method, BFCN progenitors are patterned from hESC or hiPSC
      derived primitive neuroepithelial cells, with the treatment of sonic hedgehog
      (SHH) or combination with its agonist Purmorphamine, and by co-culturing with
      human astrocytes. RESULTS: At day 20, ~90% hPSC-derived progenitors expressed
      NKX2.1, which is a transcriptional marker for MGE. Moreover, around 40% of
      NKX2.1+ cells co-expressed OLIG2 and ~15% of NKX2.1+ cells co-expressed ISLET1,
      which are ventral markers. At day 35, ~40% neurons robustly express ChAT, most of
      which are co-labeled with NKX2.1, ISLET1 and FOXG1, indicating the basal
      forebrain-like identity. At day 45, these neurons express mature neuronal markers
      MAP2, Synapsin, and VAChT. COMPARISON WITH EXISTING METHOD(S): In this method,
      undefined conditions including genetic modification or cell-sorting are avoided.
      As a choice, feeder free conditions are used to avoid ingredients of animal
      origin. Moreover, Purmorphamine can be substituted for SHH to induce ventral
      progenitors effectively and economically. CONCLUSION: We provide an efficient
      method to generate BFCNs from multiple hPSC lines, which offers the potential
      application for disease modeling and pharmacological studies.

PMID- 27036312
TI  - ARMc8: a potential diagnostic and therapeutic target for cancers.

PMID- 27036313
TI  - Localization of active, dually phosphorylated extracellular signal-regulated
      kinase 1 and 2 in colorectal cancer with or without activating BRAF and KRAS
      mutations.
AB  - Colorectal cancers (CRC) often show activating mutations of the KRAS or BRAF
      genes, which stimulate the extracellular signal-regulated kinase (ERK) pathway,
      thus increasing cell proliferation and inhibiting apoptosis. However,
      immunohistochemical results on ERK activation in such tumors differ greatly.
      Recently, using a highly optimized immunohistochemical method, we obtained
      evidence that high levels of ERK activation in rectal adenocarcinomas were
      associated with resistance to radiochemotherapy. In order to determine whether
      KRAS and/or BRAF mutations correlate to immunohistochemically detectable
      increases in phosphorylation of ERK (pERK), we stained biopsies from 36 CRC
      patients with activating mutations in the BRAF gene (BRAFV600E: BRAF(m)), the
      KRAS gene (KRAS(m)) or in neither (BRAF/KRAS(n)) with this optimized method.
      Staining was scored in blind-coded specimens by two observers. Staining of
      stromal cells was used as a positive control. BRAF(m) or KRAS(m) tumors did not
      show higher staining scores than BRAF/KRAS(n) tumors. Although BRAFV600E staining
      occurred in over 90% of cancer cells in all 9 BRAF(m) tumors, 3 only showed
      staining for pERK in less than 10% of cancer cell nuclei. The same applied to 4
      of the 14 KRAS(m) tumors. A phophorylation-insensitive antibody demonstrated that
      lack of pERK staining did not reflect defect expression of ERK1/2 protein. Thus,
      increased staining for pERK does not correlate to BRAF or KRAS mutations even
      with a highly optimized procedure. Further studies are required to determine
      whether this reflects differences in expression of counterregulatory molecules,
      including ERK phosphatases.

PMID- 27036314
TI  - Tumor progression in DICER1-mutated cystic nephroma-witnessing the genesis of
      anaplastic sarcoma of the kidney.
AB  - We report a 7-month-old female infant with a multicystic left renal tumor having
      histologic features predominantly of a cystic nephroma, but with microscopic
      cellular foci which contained atypical mitotic figures and anaplastic nuclei.
      Immunohistochemistry showed strong p53 reactivity in the anaplastic region.
      DICER1 sequencing confirmed 2 mutations: germ line mutation c.2450delC and
      c.5438A>G somatic within the tumor. Despite an initial consideration of cystic
      partially differentiated nephroblastoma, the presence of anaplasia ruled that
      possibility out, as this is not an acceptable feature for that diagnosis.
      Moreover, the germ line DICER1 mutation prompted consideration that this case
      represents a unique "nascent" anaplastic sarcoma of kidney, and further
      immunohistochemical workup demonstrated cytoplasmic, but no nuclear WT-1
      reactivity in the cellular foci. The importance of meticulous sampling of cystic
      lesions is highlighted by this unprecedented case, which lends support to the
      recent recognition of anaplastic sarcoma of kidney as a DICER1-associated cancer.

PMID- 27036315
TI  - ARMc8: a potential diagnostic and therapeutic target for cancers-reply.

PMID- 27036316
TI  - Translating the vaginal microbiome: gaps and challenges.
AB  - Management, manipulation, and restoration of a robust vaginal microbiota has the
      potential to vastly improve women's health and disease prevention. However, a
      systems level understanding of how the vaginal microbiota is associated with
      gynecologic and reproductive health is still needed to develop effective
      interventional strategies. 

PMID- 27036317
TI  - Continuous venovenous hemofiltration decreases mortality and ameliorates acute
      lung injury in canine model of severe salt water drowning.
AB  - BACKGROUND: Pulmonary edema is an important cause of complications and death in
      severe drowning. Continuous veno-venous hemofiltration (CVVH) may reduce
      pulmonary edema and thus may be a treatment modality for severe sea water
      drowning resuscitation. METHOS: 20 dogs were anesthetized and tracheally
      intubated. 10 ml/kg of sea water was infused into trachea in a minute. All
      animals developed signs of respiratory distress and severe hypoxia (PaO2 < 40
      mmHg) within 15 minutes after infusion. They were then mechanical ventilated and
      randomized to receive either CVVH (n = 10) or no additional treatment (control, n
      = 10) and followed over 4 hours. Arterial gas, hemodynamic parameters, and the
      levels of circulating inflammatory cytokines including interleukin 6 (IL-6),
      interleukin 8 (IL-8), and tumor necrosis factor alpha (TNFalpha) were determined.
      Additionally, blood endothelin and the levels of oxidative stress in lung were
      measured at sacrifice. RESULTS: 5 animals in the control group (50%) died within
      4 hours after sea water aspiration, while 10 animals received CVVH all survived
      (p < 0.05). Importantly, CVVH significantly improved blood gas exchange as
      evidenced by higher PaO2, normal oxygen saturation, and no carbon dioxide
      retention after 3 hour of CVVH, while also correcting against acidosis. Levels of
      circulating IL-6, IL-8, and TNFalpha were elevated in control but not in CVVH
      group (p < 0.01). CVVH also reduced plasma endothelin and alleviated oxidative
      stress. Histology examination further revealed reductions in pulmonary alveolar
      injury, blood congestion, and inflammation by CVVH. DISCUSSION AND CONCLUSIONS:
      CVVH decreased mortality and pulmonary injury and largely maintained hemodynamic
      and acid-base balance in animals with severe sea water drowning and thus, may be
      added as a new measure to aid in resuscitation from severe sea water drowning.
      TRIAL REGISTRATION: Animal protocol number: FZG0001859 http://www.fzzyy.com.

PMID- 27036318
TI  - Respiratory muscle strength is not decreased in patients undergoing cardiac
      surgery.
AB  - BACKGROUND: Postoperative pulmonary impairments are significant complications
      after cardiac surgery. Decreased respiratory muscle strength could be one reason
      for impaired lung function in the postoperative period. The primary aim of this
      study was to describe respiratory muscle strength before and two months after
      cardiac surgery. A secondary aim was to describe possible associations between
      respiratory muscle strength and lung function. METHODS: In this prospective
      observational study 36 adult cardiac surgery patients (67 +/- 10 years) were
      studied. Respiratory muscle strength and lung function were measured before and
      two months after surgery. RESULTS: Pre- and postoperative respiratory muscle
      strength was in accordance with predicted values; MIP was 78 +/- 24 cmH2O
      preoperatively and 73 +/- 22 cmH2O at two months follow-up (p = 0.19). MEP was
      122 +/- 33 cmH2O preoperatively and 115 +/- 38 cmH2O at two months follow-up (p =
      0.18). Preoperative lung function was in accordance with predicted values, but
      was significantly decreased postoperatively. At two-months follow-up there was a
      moderate correlation between MIP and FEV1 (r = 0.43, p = 0.009). CONCLUSIONS:
      Respiratory muscle strength was not impaired, either before or two months after
      cardiac surgery. The reason for postoperative lung function alteration is not yet
      known. Interventions aimed at restore an optimal postoperative lung function
      should focus on other interventions then respiratory muscle strength training.

PMID- 27036319
TI  - HLA-DRB1*03 as a risk factor for microalbuminuria in same duration of type 1
      diabetes: a case control study.
AB  - BACKGROUND: Increased urinary albumin excretion rate is the earliest clinical
      manifestation of diabetic nephropathy. The development of microalbuminuria in
      patients with type 1 diabetes mellitus (T1D) usually begins 5 to 15 years after
      the onset of diabetes. The rate of progression of diabetic nephropathy varies
      considerably among patients and not always can be explained solely by glycaemic
      control. The evidence suggests that genetic susceptibility may play a role in the
      development of diabetes microvascular complications, besides the presence of such
      risk factors as hyperglycaemia, hypertension, dyslipidaemia and smoking. The aim
      of the study was to evaluate a link between known genetic risk factors for type 1
      diabetes mellitus (HLA-DR3/DR4) and microalbuminuria among patients with the same
      durations of diabetes. METHODS: Ninety-nine patients with T1D at the age 18-35
      years were recruited for the study. The urine albumin excretion rate was normal
      when <30 mg/24 h; microalbuminuria 30-300 mg/24 h. Genotypes were investigated in
      39 patients with normal albumin excretion rate and duration of diabetes 13.46 +/-
      3.72 years and in 60 patients with microalbuminuria and duration of diabetes
      15.28 +/- 4.08 years (p = 0.11). Genetic typing of DR3 and DR4 antigens
      successfully was performed for 99 subjects. Statistical analysis was performed
      using SPSS v. 20.0. RESULTS: Genotyping of 99 patients with T1D was performed: no
      DR3 and DR4 risk alleles were found in 22 (22.22 %) cases, DR3 alleles were
      present in 47 (47.48 %) cases, DR4 alleles in 25 (25.25 %) cases, and DR3/DR4
      alleles in 5 (5.05 %) cases. The highest 24 h albumin excretion rate was found in
      patients with DRB1 gene expressed DR3 risk alleles group, the lowest - in
      patients with DRB1 gene with no expression of both DR3 and DR4 antigen. We
      confirmed the 1.87 (p = 0.021) increased relative risk for microalbuminuria in
      patients with DR3/DR3 alleles and same duration of diabetes. The distribution of
      DR3 and DR4 risk alleles was not associated with cardiovascular autonomic
      neuropathy both in patients with normal albumin excretion rate and
      microalbuminuria (1.6 vs 2.1; p = 0.21). CONCLUSIONS: The 1.87 (p = 0.021)
      increased relative risk for microalbuminuria was found in patients with DR3/DR3
      alleles and the same duration of diabetes.

PMID- 27036323
TI  - A heat-inactivated H7N3 vaccine induces cross-reactive cellular immunity in HLA
      A2.1 transgenic mice.
AB  - BACKGROUND: Cross-reactive immunity against heterologous strains of influenza
      virus has the potential to provide partial protection in individuals that lack
      the proper neutralizing antibodies. In particular, the boosting of memory CD8+ T
      cell responses to conserved viral proteins can attenuate disease severity caused
      by influenza virus antigenic variants or pandemic strains. However, little is yet
      known about which of these conserved internal antigens would better induce and/or
      recall memory CD8+ T cells after in vivo administration of an inactivated whole
      virus vaccine. METHODS: We explored the CD8 + T cell responses to selected
      epitopes of the internal proteins of an H7N3 influenza virus that were cross
      reactive with A/PR/8/34 virus in HLA-A2.1 transgenic (AAD) mice. RESULTS: CD8+ T
      cells against dominant and subdominant epitopes were detected upon infection of
      mice with live H7N3 virus, whereas immunization with non-replicating virus
      elicited CD8+ T cell responses against mostly immunodominant epitopes, which were
      rapidly recalled following infection with A/PR/8/34 virus. These vaccine-induced
      T cell responses were able to reduce the lung viral load in mice challenged
      intranasally with the heterologous influenza virus. CONCLUSIONS: A single
      immunization with non-replicating influenza virus vaccines may be able to elicit
      or recall cross-reactive CD8+ T cell responses to conserved immunodominant
      epitopes and, to some extent, counteract an infection by heterologous virus.

PMID- 27036324
TI  - Geographical distribution of Amblyomma cajennense (sensu lato) ticks
      (Parasitiformes: Ixodidae) in Brazil, with description of the nymph of A.
      cajennense (sensu stricto).
AB  - BACKGROUND: Until recently, Amblyomma cajennense (Fabricius, 1787) was considered
      to represent a single tick species in the New World. Recent studies have split
      this taxon into six species. While the A. cajennense species complex or A.
      cajennense (sensu lato) (s.l.) is currently represented by two species in Brazil,
      A. cajennense (sensu stricto) (s.s.) and Amblyomma sculptum Berlese, 1888, their
      geographical distribution is poorly known. METHODS: The distribution of the A.
      cajennense (s.l.) in Brazil was determined by morphological examination of all
      lots of A. cajennense (s.l.) in two large tick collections of Brazil, and by
      collecting new material during three field expeditions in the possible transition
      areas between the distribution ranges of A. cajennense (s.s.) and A. sculptum.
      Phylogenetic analysis inferred from the ITS2 rRNA gene was used to validate
      morphological results. Morphological description of the nymphal stage of A.
      cajennense (s.s.) is provided based on laboratory-reared specimens. RESULTS: From
      the tick collections, a total 12,512 adult ticks were examined and identified as
      312 A. cajennense (s.s.), 6,252 A. sculptum and 5,948 A. cajennense (s.l.). A
      total of 1,746 ticks from 77 localities were collected during field expeditions,
      and were identified as 249 A. cajennense (s.s.), 443 A. sculptum, and 1,054 A.
      cajennense (s.l.) [these A. cajennense (s.l.) ticks were considered to be males
      of either A. cajennense (s.s.) or A. sculptum]. At least 23 localities contained
      the presence of both A. cajennense (s.s.) and A. sculptum in sympatry. DNA
      sequences of the ITS2 gene of 50 ticks from 30 localities confirmed the results
      of the morphological analyses. The nymph of A. cajennense (s.s.) is
      morphologically very similar to A. sculptum. CONCLUSION: Our results confirmed
      that A. cajennense (s.l.) is currently represented in Brazil by only two species,
      A. cajennense (s.s.) and A. sculptum. While these species have distinct
      distribution areas in the country, they are found in sympatry in some transition
      areas. The current distribution of A. cajennense (s.l.) has important
      implications to public health, since in Brazil A. sculptum is the most important
      vector of the bacterium Rickettsia rickettsii, the etiological agent of Brazilian
      spotted fever.

PMID- 27036325
TI  - Opportunities for Web-based Drug Repositioning: Searching for Potential
      Antihypertensive Agents with Hypotension Adverse Events.
AB  - BACKGROUND: Drug repositioning refers to the process of developing new
      indications for existing drugs. As a phenotypic indicator of drug response in
      humans, clinical side effects may provide straightforward signals and unique
      opportunities for drug repositioning. OBJECTIVE: We aimed to identify drugs
      frequently associated with hypotension adverse reactions (ie, the opposite
      condition of hypertension), which could be potential candidates as
      antihypertensive agents. METHODS: We systematically searched the electronic
      records of the US Food and Drug Administration (FDA) Adverse Event Reporting
      System (FAERS) through the openFDA platform to assess the association between
      hypotension incidence and antihypertensive therapeutic effect regarding a list of
      683 drugs. RESULTS: Statistical analysis of FAERS data demonstrated that those
      drugs frequently co-occurring with hypotension events were more likely to have
      antihypertensive activity. Ranked by the statistical significance of frequent
      hypotension reporting, the well-known antihypertensive drugs were effectively
      distinguished from others (with an area under the receiver operating
      characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77).
      In addition, we found a series of antihypertensive agents (particularly drugs
      originally developed for treating nervous system diseases) among the drugs with
      top significant reporting, suggesting the good potential of Web-based and data
      driven drug repositioning. CONCLUSIONS: We found several candidate agents among
      the hypotension-related drugs on our list that may be redirected for lowering
      blood pressure. More important, we showed that a pharmacovigilance system could
      alternatively be used to identify antihypertensive agents and sustainably create
      opportunities for drug repositioning.

PMID- 27036326
TI  - Morphology and MMP-9, AR and IGFR-1 responses of the seminal vesicle in TRAMP
      mice model.
AB  - Seminal vesicles are important hormone-dependent accessory sex glands. Transgenic
      adenocarcinoma of the mouse prostate (TRAMP) model has been used to evaluate
      malignant diseases in the prostate and in other sexual glands. The aim of this
      study was to characterize structural and molecular features of the seminal
      vesicle in different life periods of the TRAMP mice. Groups: Control Group (5
      FVB/12 week old mice), TRAMP 12 and 22 Groups (10 TRAMP 12 and 22 week old mice,
      respectively). Seminal vesicles were evaluated by morphological and
      immunohistochemical parameters; androgenic receptor (AR), Insulin-like growth
      factor 1 (IGFR-1) and metalloproteinase 9 (MMP-9). The TRAMP mice showed frequent
      epithelial proliferation, including cellular stromal invasion, especially in the
      TRAMP 22 group. Intense AR reactivity was seen in both stroma and epithelial
      regions in the TRAMP 22 group. Intense IGFR-1 and MMP-9 stromal immunolabeling
      was identified in both TRAMP groups. Thus, there were structural and molecular
      changes in the seminal vesicle in TRAMP mice, compromising not only the structure
      but also the stromal signaling, damaging thus the function and leading to
      glandular lesions. TRAMP mice could be indicated as a good model to study
      alterations of the seminal vesicle in association to prostate cancer. 

PMID- 27036327
TI  - 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and
      apoptosis in adult male albino rats.
AB  - Ginger or Zingiber officinale which is used in traditional medicine has been
      found to possess antioxidant effect that can control the generation of free
      radicals. Free radicals are the causes of renal cell degeneration that leads to
      renal failure in case of gentamicin induced toxicity. This study was done to
      evaluate the possible protective effects of 6-gingerol as natural antioxidant on
      gentamicin-induced renal cortical oxidative stress and apoptosis in adult male
      albino rats. Forty adult male albino rats were used in this study and were
      randomly divided into four groups, control group; 6-gingerol treated group;
      gentamicin treated group and protected group (given simultaneous 6-gingerol and
      gentamicin). At the end of the study, blood samples were drawn for biochemical
      study. Kidney sections were processed for histological, and immunohistochemical
      examination for caspase-3 to detect apoptosis and anti heat shock protein 47
      (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly
      significant increase in renal function tests, tubular dilatation with marked
      vacuolar degeneration and desquamation of cells, interstitial hemorrhage and
      cellular infiltration. Immunohistochemically, gentamicin treated rats showed a
      strong positive immunoreaction for caspase-3 and anti heat shock protein 47
      (HSP47). Protected rats showed more or less normal biochemical, histological, and
      immunohistochemical pictures. In conclusion, co-administration of 6-gingerol
      during gentamicin 'therapy' has a significant reno-protective effect in a rat
      model of gentamicin-induced renal damage. It is recommended that administration
      of ginger with gentamicin might be beneficial in men who receive gentamicin to
      treat infections. 

PMID- 27036328
TI  - Metabolic model of Synechococcus sp. PCC 7002: Prediction of flux distribution
      and network modification for enhanced biofuel production.
AB  - Flux Balance Analysis was performed with the Genome Scale Metabolic Model of a
      fast growing cyanobacterium Synechococcus sp. PCC 7002 to gain insights that
      would help in engineering the organism as a production host. Gene essentiality
      and synthetic lethality analysis revealed a reduced metabolic robustness under
      genetic perturbation compared to the heterotrophic bacteria Escherichia coli.
      Under glycerol heterotrophy the reducing equivalents were generated from
      tricarboxylic acid cycle rather than the oxidative pentose phosphate pathway.
      During mixotrophic growth in glycerol the photosynthetic electron transport chain
      was predominantly used for ATP synthesis with a photosystem I/photosystem II flux
      ratio higher than that observed under autotrophy. An exhaustive analysis of all
      possible double reaction knock outs was performed to reroute fixed carbon towards
      ethanol and butanol production. It was predicted that only ~10% of fixed carbon
      could be diverted for ethanol and butanol production. 

PMID- 27036329
TI  - Enhancement of fructosyltransferase and fructooligosaccharides production by A.
      oryzae DIA-MF in Solid-State Fermentation using aguamiel as culture medium.
AB  - The aim of this work was to improve the production of fructosyltransferase
      (FTase) by Solid-State Fermentation (SSF) using aguamiel (agave sap) as culture
      medium and Aspergillus oryzae DIA-MF as producer strain. SSF was carried out
      evaluating the following parameters: inoculum rate, incubation temperature,
      initial pH and packing density to determine the most significant factors through
      Box-Hunter and Hunter design. The significant factors were then further optimized
      using a Box-Behnken design and response surface methodology. The maximum FTase
      activity (1347U/L) was obtained at 32 degrees C, using packing density of
      0.7g/cm(3). Inoculum rate and initial pH had no significant influence on the
      response. FOS synthesis applying the enzyme produced by A. oryzae DIA-MF was also
      studied using aguamiel as substrate. 

PMID- 27036330
TI  - Harvesting of microalgal biomass: Efficient method for flocculation through pH
      modulation.
AB  - Harvesting of the micro alga Chlorococcum sp. R-AP13 through autoflocculation,
      chemical flocculants or by change in medium pH was evaluated. Surface charge of
      algal cells changed in response to the method used and affected flocculation
      efficiency. While aluminum sulfate and FeCl3 supported 87% and 92% efficiency,
      auto flocculation could recover 75% of biomass in 10min. Maximum efficiency (94%)
      was obtained with change in medium pH from 8.5 to 12.0 achieved through addition
      of 40mgl(-1) of NaOH. Since high concentrations of FeCl3 and AlSO4 were toxic to
      the cells, flocculation induced by pH change may be considered the most effective
      strategy. Residual medium after flocculation could be reused efficiently for
      algal cultivation, minimizing the demand for fresh water. 

PMID- 27036331
TI  - Polyphenols content of spent coffee grounds subjected to physico-chemical
      pretreatments influences lignocellulolytic enzymes production by Bacillus sp. R2.
AB  - The objective of this study was to investigate the impact of polyphenols content
      changes issued after physico-chemical treatments of spent coffee grounds on
      lignocellulolytic enzymes production by Bacillus sp. R2. Total polyphenols of the
      collected substrates were extracted with water under autoclaving conditions.
      Results showed that polyphenols content of spent coffee grounds decreased with
      continued treatments. Untreated spent coffee grounds were the best substrate for
      cellulase and pectinase (1.33+/-0.06MU/ml and 0.32+/-0.02MU/ml respectively). A
      strong positive correlation was noticed between polyphenols content and cellulase
      and pectinase activities. However, xylanase and peroxidase correlated moderately
      with polyphenols content and their highest activities were registered with spent
      coffee grounds treated with boiling water and 1% EDTA (0.31+/-0.002MU/ml and
      15.56+/-0.56MU/ml respectively). The obtained results indicate that polyphenols
      content of the pretreated substrates influences the production of
      lignocellulolytic enzymes by Bacillus sp. R2. 

PMID- 27036332
TI  - Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month
      toxicity study in dogs.
AB  - DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic
      acid manufactured from the microalgal oil. The objective of the 9-month study was
      to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000
      and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any
      findings after a 2-month recovery period. DHA-EE was well tolerated at all doses.
      There were observations of dry flaky skin with occasional reddened areas at doses
      >=1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no
      longer present after the recovery period. There were no toxicologically relevant
      findings in body weights, body weight gains, food consumption, ophthalmological
      examinations, and ECG measurements. Test article-related changes in hematology
      parameters were limited to decreases in reticulocyte count in the high-dose males
      and considered non-adverse. In clinical chemistry parameters, dose-related
      decreases in cholesterol and triglycerides levels were observed at all doses in
      males and females and attributed to the known lipid-lowering effects of DHA.
      There were no effects on other clinical chemistry, urinalysis or coagulation
      parameters. There were no abnormal histopathology findings attributed to test
      article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000
      mg/kg bw/day for both genders. 

PMID- 27036333
TI  - Costs, compassion, and the case for vaccination.

PMID- 27036334
TI  - World TB Day 2016--advancing global tuberculosis control efforts.

PMID- 27036335
TI  - Time to define leprosy elimination as zero leprosy transmission?

PMID- 27036336
TI  - A hepatitis-free future: strategy first, then pricing.

PMID- 27036337
TI  - Control of meningitis outbreaks in the African meningitis belt.

PMID- 27036338
TI  - Corrections.

PMID- 27036339
TI  - Extensively drug-resistant tuberculosis in a young child.

PMID- 27036340
TI  - How to minimise antibiotic resistance.

PMID- 27036341
TI  - Non-randomised Ebola trials--lessons for optimal outbreak research.

PMID- 27036342
TI  - BCG vaccination: a long-lasting protection against tuberculosis?--Authors' reply.

PMID- 27036343
TI  - BCG vaccination: a long-lasting protection against tuberculosis?

PMID- 27036344
TI  - Is introduction of IPV "Good news for billions of children"?

PMID- 27036345
TI  - Is introduction of IPV "Good news for billions of children"?--Author's reply.

PMID- 27036346
TI  - New antimicrobials--lots of talk, where is the action?

PMID- 27036347
TI  - Highlights from the 23rd CROI.

PMID- 27036348
TI  - Antibiotics need guardians.

PMID- 27036355
TI  - Prevention of early episodes of otitis media by pneumococcal vaccines might
      reduce progression to complex disease.
AB  - Otitis media is a common childhood infection of the middle ear and a major cause
      of morbidity. This multifactorial disease manifests as a spectrum of clinical
      syndromes from uncomplicated acute otitis media to more complex recurrent and
      chronic cases (frequently polymicrobial), with the major pathogens involved being
      Streptococcus pneumoniae and non-typeable Haemophilus influenzae. Pneumococcal
      conjugate vaccines (PCVs) target only a few serotypes that cause otitis media;
      however, results from studies suggest that existing PCVs can prevent early
      episodes of disease associated with vaccine serotypes, resulting in a reduction
      of subsequent complex cases caused by non-vaccine serotypes and other
      otopathogens, which contribute considerably to the disease burden. In this
      Review, we discuss the role of pneumococcus in the disease continuum and assess
      clinical evidence showing the effect of prevention of early episodes on the
      complex interplay between bacterial species implicated in otitis media. 

PMID- 27036356
TI  - Antibiotic reimbursement in a model delinked from sales: a benchmark-based
      worldwide approach.
AB  - Despite the life-saving ability of antibiotics and their importance as a key
      enabler of all of modern health care, their effectiveness is now threatened by a
      rising tide of resistance. Unfortunately, the antibiotic pipeline does not match
      health needs because of challenges in discovery and development, as well as the
      poor economics of antibiotics. Discovery and development are being addressed by a
      range of public-private partnerships; however, correcting the poor economics of
      antibiotics will need an overhaul of the present business model on a worldwide
      scale. Discussions are now converging on delinking reward from antibiotic sales
      through prizes, milestone payments, or insurance-like models in which innovation
      is rewarded with a fixed series of payments of a predictable size. Rewarding all
      drugs with the same payments could create perverse incentives to produce drugs
      that provide the least possible innovation. Thus, we propose a payment model
      using a graded array of benchmarked rewards designed to encourage the development
      of antibiotics with the greatest societal value, together with appropriate
      worldwide access to antibiotics to maximise human health. 

PMID- 27036357
TI  - An unusual pathogen for prosthetic joint infection.

PMID- 27036358
TI  - Tuberculosis--advances in development of new drugs, treatment regimens, host
      directed therapies, and biomarkers.
AB  - Tuberculosis is the leading infectious cause of death worldwide, with 9.6 million
      cases and 1.5 million deaths reported in 2014. WHO estimates 480,000 cases of
      these were multidrug resistant (MDR). Less than half of patients who entered into
      treatment for MDR tuberculosis successfully completed that treatment, mainly due
      to high mortality and loss to follow-up. These in turn illustrate weaknesses in
      current treatment regimens and national tuberculosis programmes, coupled with
      operational treatment challenges. In this Review we provide an update on recent
      developments in the tuberculosis drug-development pipeline (including new and
      repurposed antimicrobials and host-directed drugs) as they are applied to new
      regimens to shorten and improve outcomes of tuberculosis treatment. Several new
      or repurposed antimicrobial drugs are in advanced trial stages for MDR
      tuberculosis, and two new antimicrobial drug candidates are in early-stage
      trials. Several trials to reduce the duration of therapy in MDR and drug
      susceptible tuberculosis are ongoing. A wide range of candidate host-directed
      therapies are being developed to accelerate eradication of infection, prevent new
      drug resistance, and prevent permanent lung injury. As these drugs have been
      approved for other clinical indications, they are now ready for repurposing for
      tuberculosis in phase 2 clinical trials. We assess risks associated with
      evaluation of new treatment regimens, and highlight opportunities to advance
      tuberculosis research generally through regulatory innovation in MDR
      tuberculosis. Progress in tuberculosis-specific biomarkers (including culture
      conversion, PET and CT imaging, and gene expression profiles) can support this
      innovation. Several global initiatives now provide unique opportunities to tackle
      the tuberculosis epidemic through collaborative partnerships between high-income
      countries and middle-income and low-income countries for clinical trials training
      and research, allowing funders to coordinate several national and regional
      programmes for greatest overall effect.

PMID- 27036360
TI  - Efficacy of nasal corticosteroid in preventing regrowth after adenoidectomy.
AB  - OBJECTIVE: One of the most frequent reasons of nasal obstruction and sleep apnea
      in pediatrics is adenoid hypertrophy. Remaining adenoid tissue can reoccur
      following hypertrophied adenoid removal and a second operation may be needed.
      Nasal corticosteroids are utilized in order to reduce adenoid hypertrophy and
      eliminate adenoidectomy operation. The purpose of our study is to assess the
      effect of nasal corticosteroid administration after adenoidectomy on adenoid
      regrowth and symptom scores. MATERIAL AND METHOD: Seventy patients who had
      adenoidectomy were enrolled in our study. Patients were divided into two groups.
      Group I (35 patients) received Mometasone furoate (40mcg/day per nostril)
      intranasal spray for 6 months, starting at postoperative week 3 after wound
      healing. As for Group II (35 patients), they received intranasal saline spray.
      Patients were followed up for one year. Every patient had flexible nasal
      endoscopy at postoperative week 3 and one year after the operation. Choana was
      scored according to its occlusion level by the adenoid tissue. Additionally,
      nasal obstruction symptoms (nasal congestion, dry mouth, snoring, nasal speaking,
      apnea and night coughing) were scored. RESULTS: Remaining adenoid tissue in the
      nasopharynx was comparable in flexible endoscopic assessment and no significant
      difference was seen between postoperative week 3 nasal obstruction scores. In the
      flexible endoscopic assessment completed in the twelfth month of the study,
      significant reduction was found in Group 1 compared to Group 2 in terms of
      adenoid size. When patients in both groups were compared, statistically
      significant reduction was observed in nasal obstruction symptom scores at the
      twelfth month. CONCLUSION: This study has demonstrated that the use of steroid
      nasal spray following adenoidectomy significantly prevents regrowth and reduces
      nasal obstruction symptoms in the early period.

PMID- 27036359
TI  - Host-directed therapies for infectious diseases: current status, recent progress,
      and future prospects.
AB  - Despite extensive global efforts in the fight against killer infectious diseases,
      they still cause one in four deaths worldwide and are important causes of long
      term functional disability arising from tissue damage. The continuing epidemics
      of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic
      pathogens represent major clinical management challenges worldwide. Newer
      approaches to improving treatment outcomes are needed to reduce the high
      morbidity and mortality caused by infectious diseases. Recent insights into
      pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's
      innate and acquired immune responses are leading to identification and
      development of a wide range of host-directed therapies with different mechanisms
      of action. Host-directed therapeutic strategies are now becoming viable adjuncts
      to standard antimicrobial treatment. Host-directed therapies include commonly
      used drugs for non-communicable diseases with good safety profiles,
      immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional
      products, and cellular therapy using the patient's own immune or bone marrow
      mesenchymal stromal cells. We discuss clinically relevant examples of progress in
      identifying host-directed therapies as adjunct treatment options for bacterial,
      viral, and parasitic infectious diseases. 

PMID- 27036361
TI  - Predictive Factors of the Survival of Women With Invasive Breast Cancer in French
      Guiana: The Burden of Health Inequalities.
AB  - BACKGROUND: The prognosis of patients with breast cancer in French Guiana is
      worse than in France, with 23 deaths per 100 incident cases versus 17 per 100 in
      metropolitan France. This study aimed to compare the relative survival of
      patients with invasive breast cancer (IBC) between women from French Guiana and
      metropolitan France and to determine risk factors influencing breast cancer
      survival in French Guiana. MATERIALS AND METHODS: Data were collected from the
      Cancer Registry of French Guiana. We compared the relative survival of women with
      IBC between French Guiana and metropolitan France. We used the Cox proportional
      hazard regression to evaluate the effect of prognostic factors on cancer-specific
      mortality in French Guiana. RESULTS: We included all 269 cases of IBC in women
      diagnosed in French Guiana between 2003 and 2009. The overall 5-year relative
      survival rate of patients with IBC was 79% in French Guiana and 86% in
      metropolitan France. The place of birth (foreign country vs. French territory),
      the tumor stage at the time of diagnosis, the mode of diagnosis (symptoms vs.
      screening), the presence of hormone receptors in the tumor, and the histologic
      type were the variables associated with survival differences. None of the other
      study variables were significantly associated with prognosis. CONCLUSION: Access
      to care for migrants is challenging, which leads to health inequalities. Early
      detection through prevention programs is crucial to increase IBC survival,
      notably for foreign-born patients.

PMID- 27036362
TI  - The role of mitochondria in plant development and stress tolerance.
AB  - Eukaryotic cells require orchestrated communication between nuclear and
      organellar genomes, perturbations in which are linked to stress response and
      disease in both animals and plants. In addition to mitochondria, which are found
      across eukaryotes, plant cells contain a second organelle, the plastid. Signaling
      both among the organelles (cytoplasmic) and between the cytoplasm and the nucleus
      (i.e. nuclear-cytoplasmic interactions (NCI)) is essential for proper cellular
      function. A deeper understanding of NCI and its impact on development, stress
      response, and long-term health is needed in both animal and plant systems. Here
      we focus on the role of plant mitochondria in development and stress response. We
      compare and contrast features of plant and animal mitochondrial genomes (mtDNA),
      particularly highlighting the large and highly dynamic nature of plant mtDNA.
      Plant-based tools are powerful, yet underutilized, resources for enhancing our
      fundamental understanding of NCI. These tools also have great potential for
      improving crop production. Across taxa, mitochondria are most abundant in cells
      that have high energy or nutrient demands as well as at key developmental time
      points. Although plant mitochondria act as integrators of signals involved in
      both development and stress response pathways, little is known about plant mtDNA
      diversity and its impact on these processes. In humans, there are strong
      correlations between particular mitotypes (and mtDNA mutations) and developmental
      differences (or disease). We propose that future work in plants should focus on
      defining mitotypes more carefully and investigating their functional implications
      as well as improving techniques to facilitate this research.

PMID- 27036363
TI  - Mitophagy receptors sense stress signals and couple mitochondrial dynamic
      machinery for mitochondrial quality control.
AB  - Mitochondria are essential organelles for many fundamental cellular processes,
      including energy production, fatty acid beta-oxidation, metabolite synthesis,
      iron and calcium homeostasis, and programmed cell death. Mitochondrial quality
      thus influences not only individual cell functions but also whole body
      metabolism. Dysregulated mitochondrial quality control is closely associated with
      the progression of aging related diseases, such as cancers and neurodegenerative
      disorders. Mitochondrial quality is monitored at the protein, organelle and sub
      organelle levels. The critical issues are how stresses such as bioenergetic
      stress, oxidative stress and proteotoxic stress, are sensed and how the
      mitochondrial events are coordinated. Recently, several receptors were identified
      to mediate selective mitophagy, which is essential for mitochondrial quality
      control in yeast and mammalian cells. It is emerging that these receptors sense
      distinct stress signals and couple mitophagy machineries with mitochondrial
      fission/fusion machineries for mitochondrial quality control. Herein, we will
      review recent advances in receptors mediated mitophagy and mitochondrial dynamics
      for mitochondrial quality control, with attempt to have an integrative view on
      the molecular mechanisms for mitochondrial quality control.

PMID- 27036364
TI  - A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced
      hepatic glutathione synthesis.
AB  - Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty
      liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular
      oxidative defense, however there are currently no simple non-invasive methods for
      assessing hepatic glutathione metabolism in patients with NAFLD. As a primary
      source of plasma glutathione, liver plays an important role in interorgan
      glutathione homeostasis. In this study, we have tested the hypothesis that
      measurements of plasma glutathione turnover could be used to assess the hepatic
      glutathione metabolism in LDLR(-/)(-) mice, a mouse model of diet-induced NAFLD.
      Mice were fed a standard low fat diet (LFD) or a high fat diet containing
      cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma
      glutathione were quantified using the (2)H2O metabolic labeling approach. Our
      results show that a WD leads to reduced fractional synthesis rates (FSR) of
      hepatic (25%/h in LFD vs. 18%/h in WD, P<0.05) and plasma glutathione (43%/h in
      LFD vs. 21%/h in WD, P<0.05), without any significant effect on their absolute
      production rates (PRs). WD-induced concordant changes in both hepatic and plasma
      glutathione turnover suggest that the plasma glutathione turnover measurements
      could be used to assess hepatic glutathione metabolism. The safety, simplicity,
      and low cost of the (2)H2O-based glutathione turnover approach suggest that this
      method has the potential for non-invasive probing of hepatic glutathione
      metabolism in patients with NAFLD and other diseases.

PMID- 27036365
TI  - Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.
AB  - Diets that boost ketone production are increasingly used for treating several
      neurological disorders. Elevation in ketones in most cases is considered
      favorable, as they provide energy and are efficient in fueling the body's energy
      needs. Despite all the benefits from ketones, the above normal elevation in the
      concentration of ketones in the circulation tend to illicit various pathological
      complications by activating injurious pathways leading to cellular damage. Recent
      literature demonstrates a plausible link between elevated levels of circulating
      ketones and oxidative stress, linking hyperketonemia to innumerable morbid
      conditions. Ketone bodies are produced by the oxidation of fatty acids in the
      liver as a source of alternative energy that generally occurs in glucose limiting
      conditions. Regulation of ketogenesis and ketolysis plays an important role in
      dictating ketone concentrations in the blood. Hyperketonemia is a condition with
      elevated blood levels of acetoacetate, 3-beta-hydroxybutyrate, and acetone.
      Several physiological and pathological triggers, such as fasting, ketogenic diet,
      and diabetes cause an accumulation and elevation of circulating ketones.
      Complications of the brain, kidney, liver, and microvasculature were found to be
      elevated in diabetic patients who had elevated ketones compared to those
      diabetics with normal ketone levels. This review summarizes the mechanisms by
      which hyperketonemia and ketoacidosis cause an increase in redox imbalance and
      thereby increase the risk of morbidity and mortality in patients.

PMID- 27036366
TI  - The antioxidant protein Oxr1 influences aspects of mitochondrial morphology.
AB  - Oxidative stress (OS) and mitochondrial dysfunction are implicated in
      neurodegenerative disease, suggesting that antioxidant defence systems are
      critical for cell survival in the central nervous system (CNS). Oxidation
      resistance 1 (OXR1) can protect against OS in cellular and mouse models of
      amyotrophic lateral sclerosis (ALS) when over-expressed, whereas deletion of Oxr1
      in mice causes neurodegeneration. OXR1 has emerged therefore as an essential
      antioxidant protein that controls the susceptibility of neurons to OS. It has
      been suggested that OXR1 is localised to mitochondria, yet the functional
      significance of this has not been investigated in the context of neuronal cell
      death. In order to characterise the role of Oxr1 in mitochondria, we investigated
      its sub-mitochondrial localisation and demonstrate that specific isoforms are
      associated with the outer mitochondrial membrane, while the full-length Oxr1
      protein is predominately cytoplasmic. Interestingly, cytoplamsic over-expression
      of these mitochondrially-localised isoforms was still able to protect against OS
      induced cell death and prevent rotenone-induced mitochondrial morphological
      changes. To study the consequences of Oxr1 deletion in vivo, we utilised the
      bella ataxic mouse mutant. We were unable to identify defects in mitochondrial
      metabolism in primary cerebellar granule cells (GCs) from bella mice, however a
      reduction in mitochondrial length was observed in mutant GCs compared to those
      from wild-type. Furthermore, screening a panel of proteins that regulate
      mitochondrial morphology in bella GCs revealed de-regulation of phospho
      Drp1(Ser616), a key mitochondrial fission regulatory factor. Our data provide new
      insights into the function of Oxr1, revealing that specific isoforms of this
      novel antioxidant protein are associated with mitochondria and that the
      modulation of mitochondrial morphology may be an important feature of its
      protective function. These results have important implications for the potential
      use of OXR1 in future antioxidant therapies.

PMID- 27036368
TI  - Erratum to "Exploring Variability in CT Characterization of Tumors: A Preliminary
      Phantom Study" [Transl Oncol7(1), 88-93].

PMID- 27036367
TI  - Synergistic effects of ascorbate and sorafenib in hepatocellular carcinoma: New
      insights into ascorbate cytotoxicity.
AB  - We investigated the mechanism of selective ascorbate-induced cytotoxicity in
      tumor cells, including Hep G2 cells, compared to primary hepatocytes. H2O2
      formation was required for ascorbate cytotoxicity, as extracellular catalase
      treatment protected tumor cells. H2O2 generated by glucose oxidase treatment also
      caused cell killing, but treatment with a pharmacologic dose (5-20mM) of
      ascorbate was significantly more cytotoxic at comparable rates of H2O2
      production, suggesting that ascorbate enhanced H2O2 cytotoxicity. This was
      further supported by the finding that ascorbate at a non-cytotoxic dose (1mM)
      enhanced cell killing caused by glucose oxidase. Consistent with this conclusion,
      ascorbate treatment caused deregulation of cellular calcium homeostasis,
      resulting in massive mitochondrial calcium accumulation. Ascorbate acted
      synergistically with the chemotherapeutic sorafenib in killing Hep G2 cells, but
      not primary hepatocytes, suggesting adjuvant ascorbate treatment can broaden
      sorafenib's therapeutic range. Sorafenib caused mitochondrial depolarization and
      prevented mitochondrial calcium sequestration. Subsequent ascorbate addition
      further deregulated cellular calcium homeostasis promoting cell death.
      Additionally, we present the case of a patient with hepatocellular carcinoma
      (HCC) who had prolonged regression of a rib metastasis upon combination treatment
      with ascorbate and sorafenib, indicating that these studies have direct clinical
      relevance.

PMID- 27036369
TI  - Attitudes to information technology: toys or tools?
AB  - Information systems are a powerful 'engine' of change. Managing the change
      process effectively, whilst implementing a new information system within the care
      environment, may facilitate the efficient development of quality patient care.
      Incorporating the use of a computerised information system into everyday
      professional practice, requires nurses not only to overcome any resistance to
      change, but also to become willing users and creative operators of Information
      Technology (IT). This article is a summary of research, conducted as part of a
      benefit realisation programme, set to assess practitioners' attitudes towards
      using computers within clinical settings. The study was carried out prior to the
      implementation of an information system and subjects included all grades and
      specialities of nurses and midwives working in 6 hospitals of one Scottish NHS
      Trust which provides both acute mental health and community services. This study
      confirms that a large majority of nurses and midwives have positive attitudes
      towards computer use in their practice areas. Furthermore, many care
      professionals indicated that their current manual process, involved in gathering
      patient's information, is inefficient. However, many are still unconvinced
      whether computerised systems will record workload accurately to become an
      effective clinical and management tool. The study also found that senior staff
      possess a greater degree of conviction as to the potential benefits or
      disbenefits of computer use in the delivery of care. This study, unlike similar
      research elsewhere, did not find a relationship between age and staff's attitudes
      towards computers. 

PMID- 27036370
TI  - CTGF is obligatory for TGF-beta1 mediated fibrosis in OSMF.

PMID- 27036371
TI  - Heart morphology differences induced by intrauterine growth restriction and
      preterm birth measured on the ECG at preadolescent age.
AB  - Intrauterine Growth Restriction (IUGR) and premature birth are associated with
      higher risk of cardiovascular diseases throughout adulthood. The aim of this
      study was to evaluate the influence of these factors in ventricular electrical
      remodeling in preadolescents. Electrocardiography was performed in a cohort of 33
      IUGR, 32-preterm with appropriate weight and 60 controls. Depolarization and
      repolarization processes were studied by means of the surface ECG, including
      loops and angles corresponding to QRS and T-waves. The angles between the
      dominant vector of QRS and the frontal plane XY were different among the study
      groups: controls [20.03 degrees (10.11 degrees -28.64 degrees )], preterm [25.48
      degrees (19.79 degrees -33.56 degrees )], and IUGR [27.77 degrees (16.59 degrees 
      33.23 degrees )]. When compared to controls, IUGR subjects also presented wider
      angles between the difference of QRS and T-wave dominant vectors and the XY-plane
      [5.28 degrees +/-12.15 degrees  vs 0.49 degrees +/-14.15 degrees , p<0.05] while
      preterm ones showed smaller frontal QRS-T angle [4.68 degrees (2.20 degrees 
      12.89 degrees ) vs 6.57 degrees (2.72 degrees -11.31 degrees ), p<0.05]. Thus,
      electrical remodeling is present in IUGR and preterm preadolescents, and might
      predispose them to cardiovascular diseases in adulthood. Follow-up studies are
      warranted.

PMID- 27036372
TI  - Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and
      gut tissue.
AB  - OBJECTIVES: Human leukocyte antigen (HLA)-B27 (B27) is the strongest genetic
      factor associated with development of Ankylosing Spondylitis and other
      spondyloarthropathies (SpA), yet the role it plays in disease pathogenesis
      remains unclear. We investigated the expression of potentially pathogenic non
      conventional heavy chain forms (NC) of B27 in synovial and intestinal tissues
      obtained from SpA patients. We also determined the presence of NC-B27 in joints,
      lymphoid and gastrointestinal tissue from B27 transgenic (TG(1)) rats with
      M.tuberculosis-induced SpA. METHODS: Expression of NC-B27 in human SpA joints and
      gut and in (21-3 * 283-2)F1 HLA-B27/Hubeta2m rat tissue was determined by
      immunohistochemistry, flow cytometry and confocal microscopy analysis using HC10
      and HD6 antibodies. RESULTS: Both HC10- and HD6-reactive HLA molecules were
      present in synovial tissue from SpA patients. Both NC-B27 and KIR3DL2, a ligand
      for NC-B27, were expressed in inflamed terminal ileal tissues in patients with
      early SpA. Infiltrating cells in inflamed joint tissues isolated from B27 TG(1)
      rats expressed high levels of NC-B27. NC-B27 were also expressed in joint
      resident cells from ankle and tail joints of B27 TG(1) rats prior to clinical
      arthritis. The expression of NC-B27 on B27 TG(1) rat CD11b/c(+), CD8alpha(+),
      cells from spleens and LNs increased with animal age and disease progression.
      CONCLUSIONS: Non-conventional HLA class 1 molecules are expressed on resident and
      infiltrating cells in both synovial and GI tissues in human SpA. NC-B27
      expression in joints and lymphoid tissues from B27 TG(1) rats prior to the onset
      of arthritis is consistent with the hypothesis that they play a pathogenic role
      in SpA.

PMID- 27036373
TI  - Robot assisted Aortic and Non-aortic Vascular Operations.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical experience with
      310 robot assisted vascular procedures. The da Vinci system has been used by a
      variety of disciplines for laparoscopic procedures but the use of robots in
      vascular surgery is still relatively uncommon. METHODS: From November 2005 to May
      2014, 310 robot assisted vascular operations were performed. Two hundred and
      twenty four patients were prospectively evaluated for occlusive disease, 61
      patients for abdominal aortic aneurysm, four for a common iliac artery aneurysm,
      four for a splenic artery aneurysm, one for a internal mammary artery aneurysm,
      and after the unsuccessful endovascular treatment five for hybrid procedures, two
      patients for median arcuate ligament release and nine for endoleak II treatment
      post EVAR. Among these patients, 224 underwent robotic occlusive disease
      treatment (Group I), 65 robotic aorto-iliac aneurysm surgery (Group II) and 21
      other robotic procedures (Group III). RESULTS: A total of 298 cases (96.1%) were
      successfully completed robotically. In 10 patients (3.2%) conversion was
      necessary. The 30 day mortality was 0.3%, and two (0.6%) late prosthetic
      infections were seen. Targeted Group I and Group II patients were compared.
      Robotic ilio-femoral bypass, aorto-femoral bypass, or aorto-iliac thrombo
      endarterectomy with prosthetic patch (Group I) required an operative time of 194
      (range, 127-315) minutes and robotic aorto-iliac aneurysm surgery (Group II), 253
      (range, 185-360) minutes. The mean aortic cross clamping time was 37 minutes in
      Group I and 93 minutes in Group II. The mean blood loss was more significant in
      Group II (1,210 mL) than in Group I (320 mL). CONCLUSION: From a practical point
      of view, the greatest advantage of the robot assisted procedure has been the
      speed and relative simplicity of construction of the vascular anastomosis. This
      experience with robot assisted laparoscopic surgery has demonstrated the
      feasibility of this technique in different areas of vascular surgery.

PMID- 27036374
TI  - Editor's Choice - Ex vivo Renal Artery Repair with Kidney Autotransplantation for
      Renal Artery Branch Aneurysms: Long-term Results of Sixty-seven Procedures.
AB  - OBJECTIVE/BACKGROUND: To evaluate the long-term outcome of renal
      revascularization by ex vivo renal artery reconstruction and autotransplantation
      for renal artery branch aneurysms (RABAs). METHODS: Between 1991 and 2015, 67 ex
      vivo renal artery reconstructions with kidney autotransplantation were performed
      in 55 adults (mean age 47 years) and 10 children to repair 87 RABAs. The main
      underlying disease was fibromuscular dysplasia in 34 patients. Other etiologies
      were systemic congenital disease in eight patients, spontaneous dissecting
      aneurysms in five, iatrogenic aneurysms in three, atheromatous aneurysms in two
      and unknown etiology in 13. Median RABA diameter was 20.5 mm. Fifty-three
      patients (82%) were hypertensive, 60 had normal renal function and no patient was
      on hemodialysis. Seven patients (11%) were operated on after failure of an
      endovascular procedure. The mean number of renal artery branches repaired per
      patient was 3.5 and multiple aneurysms were treated in 14 patients (22%). The
      hypogastric artery was used in 41 patients, the saphenous vein in 18, the
      superficial femoral artery in five and a combination of different materials in
      three. RESULTS: No deaths occurred during the first 30 days. Primary patency at
      30 days was 90.8% following to six early thromboses. Three patients (5%) were
      lost to follow up. No other thrombosis occurred. At 8 years, the primary and
      primary-assisted patency were 88% and 91%, respectively. Survival was 95% at 9
      years. Among the 53 hypertensive patients, two were lost to follow up. At 9
      years, 22 (43%) were cured and nine (18%) were improved with a significant
      reduction of antihypertensive medication (p < .05). The pre-operative
      modification of the diet in renal disease (MDRD) clearance was 93 +/- 29
      mL/minute, the immediate post-operative MDRD was 94 +/- 33 mL/minute, and at the
      end of follow up it was 86 +/- 26 mL/minute (p > .05). CONCLUSION: Ex vivo renal
      artery reconstruction for complex RABAs eliminates the risk of rupture, confers a
      benefit to hypertension, and preserves renal function with a satisfactory long
      term patency.

PMID- 27036375
TI  - Cardiovascular magnetic resonance demonstration of the spectrum of morphological
      phenotypes and patterns of myocardial scarring in Anderson-Fabry disease.
AB  - BACKGROUND: Although it is known that Anderson-Fabry Disease (AFD) can mimic the
      morphologic manifestations of hypertrophic cardiomyopathy (HCM) on
      echocardiography, there is a lack of cardiovascular magnetic resonance (CMR)
      literature on this. There is limited information in the published literature on
      the distribution of myocardial fibrosis in patients with AFD, with scar reported
      principally in the basal inferolateral midwall. METHODS: All patients with
      confirmed AFD undergoing CMR at our center were included. Left ventricular (LV)
      volumes, wall thicknesses and scar were analyzed offline. Patients were
      categorized into 4 groups: (1) no wall thickening; (2) concentric hypertrophy;
      (3) asymmetric septal hypertrophy (ASH); and (4) apical hypertrophy. Charts were
      reviewed for clinical information. RESULTS: Thirty-nine patients were included
      (20 males [51%], median age 45.2 years [range 22.3-64.4]). Almost half (17/39)
      had concentric wall thickening. Almost half (17/39) had pathologic LV scar; three
      quarters of these (13/17) had typical inferolateral midwall scar. A quarter
      (9/39) had both concentric wall thickening and typical inferolateral scar. A
      subgroup with ASH and apical hypertrophy (n = 5) had greater maximum wall
      thickness, total LV scar, apical scar and mid-ventricular scar than those with
      concentric hypertrophy (n = 17, p < 0.05). Patients with elevated LVMI had more
      overall arrhythmia (p = 0.007) more ventricular arrhythmia (p = 0.007) and
      sustained ventricular tachycardia (p = 0.008). CONCLUSIONS: Concentric thickening
      and inferolateral mid-myocardial scar are the most common manifestations of AFD,
      but the spectrum includes cases morphologically identical to apical and ASH
      subtypes of HCM and these have more apical and mid-ventricular LV scar.
      Significant LVH is associated with ventricular arrhythmia.

PMID- 27036376
TI  - Role of preoperative biliary stents, bile contamination and antibiotic
      prophylaxis in surgical site infections after pancreaticoduodenectomy.
AB  - BACKGROUND: The routine use of preoperative biliary drainage before
      pancreaticoduodenectomy (PD) remains controversial. This observational
      retrospective study compared stented and non-stented patients undergoing PD to
      assess any differences in post-operative morbidity and mortality. METHODS: A
      total of 180 consecutive patients who underwent PD and had intra-operative bile
      cultures performed between January 2010 and February 2013 were retrospectively
      identified. All patients received peri-operative intravenous antibiotic
      prophylaxis, primarily cefazolin. RESULTS: Overall incidence of post-operative
      surgical complications was 52.3 %, with no difference between stented and non
      stented patients (53.4 % vs. 51.1 %; p = 0.875). However, stented patients had a
      significantly higher incidence of deep incisional surgical site infections (SSIs)
      (p = 0.038). In multivariate analysis, biliary stenting was confirmed as a risk
      factor for deep incisional SSIs (p = 0.044). Significant associations were also
      observed for cardiac disease (p = 0.010) and BMI >=25 kg/m(2) (p = 0.045).
      Enterococcus spp. were the most frequent bacterial isolates in bile (74.5 %) and
      in drain fluid (69.1 %). In antimicrobial susceptibilty testing, all Enterococci
      isolates were cefazolin-resistant. CONCLUSION: Given the increased risk of deep
      incisional SSIs, preoperative biliary stenting in patients underging PD should be
      used only in selected patients. In stented patients, an antibiotic with anti
      enterococcal activity should be chosen for PD prophylaxis.

PMID- 27036377
TI  - Clinical Characteristics of Patients Carrying the Q703K Variant of the NLRP3
      Gene: A 10-year Multicentric National Study.
AB  - OBJECTIVE: The aim of our study was to analyze the clinical and functional effect
      of the p.Q703K (p. Q705K, c. 2107C>A) variant of the NLRP3 gene in a population
      of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS).
      METHODS: Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on
      clinical presentation, response to treatment, and longterm followup were
      collected using a uniform questionnaire. The pattern of cytokine secretion after
      lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients
      carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic,
      cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K,
      and compared with 7 patients with CAPS with sure pathogenic variants and 6
      healthy controls. RESULTS: The p.Q703K variant was found in 57 screened patients
      with an overall allelic frequency of 5%. The frequency in normal controls was
      5.5%. Clinical data at the moment of molecular analysis and at followup were
      available in 36 patients. Two patients displayed additional mutations of NLRP3.
      The mean followup was 2.5 years. Thirteen patients (39%) had a final diagnosis
      different from the original suspicion of CAPS. The remaining 21 patients
      displayed a mild phenotype mainly characterized by recurrent episodes of
      urticarial rash and arthralgia. Only 8 patients were treated with anti
      interleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern
      of secretion of IL-1beta and other cytokines (IL-6 and IL-1 receptor antagonist)
      in patients did not display the aberrancies observed in patients with CAPS and
      was similar to that observed in healthy controls. CONCLUSION: The present study
      confirms the weak clinical and functional effect of the p.Q703K variant.

PMID- 27036378
TI  - Identifying Targets for Improving Mental Healthcare of Adolescents with Systemic
      Lupus Erythematosus: Perspectives from Pediatric Rheumatology Clinicians in the
      United States and Canada.
AB  - OBJECTIVE: To identify targets for improving mental healthcare of adolescents
      with systemic lupus erythematosus (SLE) by assessing current practices and
      perceived barriers for mental health intervention by pediatric rheumatology
      clinicians. METHODS: Members of the Childhood Arthritis and Rheumatology Research
      Alliance (CARRA) completed a Web-based survey assessing current mental health
      practices, beliefs, and barriers. We examined associations between provider
      characteristics and the frequency of barriers to mental health screening and
      treatment using multivariable linear regression. RESULTS: Of the 375 eligible
      CARRA members, 130 responded (35%) and 119 completed the survey. Fifty-two
      percent described identification of depression/anxiety in adolescents with SLE at
      their practice as inadequate, and 45% described treatment as inadequate. Seventy
      seven percent stated that routine screening for depression/anxiety in pediatric
      rheumatology should be conducted, but only 2% routinely used a standardized
      instrument. Limited staff resources and time were the most frequent barriers to
      screening. Respondents with formal postgraduate mental health training,
      experience treating young adults, and practicing at sites with very accessible
      mental health staff, in urban locations, and in Canada reported fewer barriers to
      screening. Long waitlists and limited availability of mental health providers
      were the most frequent barriers to treatment. Male clinicians and those
      practicing in the Midwest and Canada reported fewer barriers to treatment.
      CONCLUSION: Pediatric rheumatology clinicians perceive a need for improved mental
      healthcare of adolescents with SLE. Potential strategies to overcome barriers
      include enhanced mental health training for pediatric rheumatologists,
      standardized rheumatology-based mental health practices, and better integration
      of medical and mental health services.

PMID- 27036379
TI  - Glucocorticoid Effect on Radiographic Progression in Placebo Arms of Rheumatoid
      Arthritis Biologics Trials.
AB  - OBJECTIVE: To assess the effect of glucocorticoids (GC) on damage progression in
      placebo-biologic arms of rheumatoid arthritis (RA) biologics trials. METHODS:
      Posthoc metaanalysis of 2 infliximab (IFX) trials (established and early RA) and
      1 tocilizumab (TCZ) trial (established RA). RESULTS: The proportion of patients
      receiving GC was 38%-64%, baseline damage was 11-82 Sharp/van der Heijde points,
      and progression in the placebo groups was 0.5-4.8 points in 6 months. In the
      pooled IFX studies, GC cotreatment reduced 6-month progression by 2.6 points (95%
      CI 0.6-4.5). In the TCZ study (progression rate 0.5 Genant points), no such
      difference was seen. CONCLUSION: GC cotreatment may affect results in RA trials.

PMID- 27036380
TI  - Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early
      Rheumatoid Arthritis Are Associated with Autoantibody Status.
AB  - OBJECTIVE: The role of natural killer (NK) cells in the immunopathogenesis of
      rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional
      alterations of CD56(dim) and CD56(bright) NK cells in the early stages of RA
      development were studied. METHODS: Whole blood samples from newly diagnosed,
      treatment-naive, seropositive (SP) and seronegative (SN) patients with RA (SP RA,
      n = 45 and SN RA, n = 12), patients with SP arthralgia (n = 30), and healthy
      controls (HC, n = 41) were assessed for numbers and frequencies of T cells, B
      cells, and NK cells. SP status was defined as positive for anticyclic
      citrullinated peptide antibodies (anti-CCP) and/or rheumatoid factor (RF).
      Peripheral blood mononuclear cells were used for further analysis of NK cell
      phenotype and function. RESULTS: Total NK cell numbers were decreased in SP RA
      and SP arthralgia but not in SN RA. Also, NK cells from SP RA showed a decreased
      potency for interferon-gamma (IFN-gamma) production. A selective decrease of
      CD56(dim), but not CD56(bright), NK cells in SP RA and SP arthralgia was
      observed. This prompted investigation of CD16 (FcgammaRIIIa) triggering in NK
      cell apoptosis and cytokine expression. In vitro, CD16 triggering induced
      apoptosis of CD56(dim) but not CD56(bright) NK cells from HC. This apoptosis was
      augmented by adding interleukin 2 (IL-2). Also, CD16 triggering in the presence
      of IL-2 stimulated IFN-gamma and tumor necrosis factor-alpha expression by
      CD56(dim) NK cells. CONCLUSION: The decline of CD56(dim) NK cells in SP
      arthralgia and SP RA and the in vitro apoptosis of CD56(dim) NK cells upon CD16
      triggering suggest a functional role of immunoglobulin G-containing autoantibody
      (anti-CCP and/or RF)-immune complexes in this process. Moreover, CD16-triggered
      cytokine production by CD56(dim) NK cells may contribute to systemic inflammation
      as seen in SP arthralgia and SP RA.

PMID- 27036381
TI  - Pulmonary Involvement in the Antisynthetase Syndrome: A Comparative Cross
      sectional Study.
AB  - OBJECTIVE: Interstitial lung disease (ILD) is a major component of the
      antisynthetase syndrome, but quantitative data on longterm pulmonary outcome in
      antisynthetase syndrome are limited. In this study, the main aims were to compare
      pulmonary function tests (PFT) and the 6-min walking distance (6MWD) between
      patients with antisynthetase syndrome and healthy sex- and age-matched controls,
      to evaluate the extent of ILD by lung high-resolution computed tomography (HRCT),
      and to assess correlations between PFT measures and ILD extent. METHODS:
      Concurrent PFT and 6MWD were performed in 68 patients with antisynthetase
      syndrome and their individually matched controls. Additionally, in the patients,
      the extent of ILD was determined in 10 HRCT sections, expressed as percentage of
      total lung volumes. RESULTS: Median disease duration in the antisynthetase
      syndrome cohort was 71 months. Compared with the matched controls, the patients
      with antisynthetase syndrome had mean 28%, 27%, and 53% lower absolute values of
      forced vital capacity (FVC), forced expiratory volume in 1 s, and DLCO (p <
      0.001). Mean difference in 6MWD between patients and controls was 116 m (p <
      0.001). Median extent of ILD by HRCT was 20% (range 0-73) and correlated with FVC
      and DLCO. Pulmonary outcome did not differ between Jo1 and non-Jo1 subsets.
      CONCLUSION: To our knowledge, this study is the first to demonstrate a highly
      significant difference in PFT between patients with antisynthetase syndrome with
      6 years of followup and healthy controls. DLCO displayed the highest difference
      with mean 53% lower value in the patients. FVC and DLCO correlated significantly
      with ILD extent, indicating these variables as appropriate outcome measures in
      antisynthetase syndrome-associated ILD.

PMID- 27036382
TI  - Measuring the Rheumatology Workforce in Canada: A Literature Review.
AB  - OBJECTIVE: The number of rheumatologists per capita has been proposed as a
      performance measure for arthritis care. This study reviews what is known about
      the rheumatologist workforce in Canada. METHODS: A systematic search was
      conducted in EMBASE and MEDLINE using the search themes "rheumatology" AND
      "workforce" AND "Canada" from 2000 until December 2014. Additionally, workforce
      databases and rheumatology websites were searched. Data were abstracted on the
      numbers of rheumatologists, demographics, retirement projections, and barriers to
      healthcare. RESULTS: Twenty-five sources for rheumatology workforce information
      were found: 6 surveys, 14 databases, 2 patient/provider resources, and 3
      epidemiologic studies. Recent estimates say there are 398 to 428 rheumatologists
      in Canada, but there were limited data on allocation of time to clinical
      practice. Although the net number of rheumatologists has increased, the mean age
      was >= 47.7 years, and up to one-third are planning to retire in the next decade.
      There is a clustering of rheumatologists around academic centers, while some
      provinces/territories have suboptimal ratios of rheumatologists per capita (range
      0-1.1). Limited information was found on whether rural areas are receiving
      adequate services. The most consistent barrier reported by rheumatologists was
      lack of allied health professionals. CONCLUSION: In Canada there are regional
      disparities in access to rheumatologist care and an aging rheumatologist
      workforce. To address these workforce capacity issues, better data are needed
      including information on clinical full-time equivalents, delivery of care to
      remote communities, and use of alternative models of care to increase clinical
      capacity.

PMID- 27036383
TI  - Copy Number Variation of HLA-DQA1 and APOBEC3A/3B Contribute to the
      Susceptibility of Systemic Sclerosis in the Chinese Han Population.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a systemic connective tissue disease
      caused by a genetic aberrant. The involvement of the copy number variations (CNV)
      in the pathogenesis of SSc is unclear. We tried to identify some CNV that are
      involved with the susceptibility to SSc. METHODS: A genome-wide CNV screening was
      performed in 20 patients with SSc. Five SSc-associated common CNV that included
      HLA-DRB5, HLA-DQA1, IRGM, CDC42EP3, and APOBEC3A/3B were identified from the
      screening and were then validated in 365 patients with SSc and 369 matched
      healthy controls. RESULTS: Three hundred forty-four CNV (140 gains and 204
      losses) and 2 CNV hotspots (6q21.3 and 22q11.2) were found in the SSc genomes
      (covering 24.2 megabases), suggesting that CNV were ubiquitous in the SSc genome
      and played important roles in the pathogenesis of SSc. The high copy number of
      HLA-DQA1 was a significantly protective factor for SSc (OR 0.07, p = 2.99 * 10(
      17)), while the high copy number of APOBEC3A/B was a significant risk factor (OR
      3.45, p = 6.4 * 10(-18)), adjusted with sex and age. The risk prediction model
      based on genetic factors in logistic regression showed moderate prediction
      ability, with area under the curve = 0.80 (95% CI 0.77-0.83), which demonstrated
      that APOBEC3A/B and HLA-DQA1 were powerful biomarkers for SSc risk evaluation and
      contributed to the susceptibility to SSc. CONCLUSION: CNV of HLA-DQA1 and
      APOBEC3A/B contribute to the susceptibility to SSc in a Chinese Han population.

PMID- 27036384
TI  - Sustained Remission Improves Physical Function in Patients with Established
      Rheumatoid Arthritis, and Should Be a Treatment Goal: A Prospective Observational
      Cohort Study from Southern Sweden.
AB  - OBJECTIVE: It has been proposed that remission should be maintained throughout
      the course of rheumatoid arthritis (RA); however, the evidence supporting this is
      limited. Physical function measured by the Health Assessment Questionnaire (HAQ)
      is a major outcome in RA, and HAQ is shown to be one of the strongest predictors
      of longterm outcomes. The purpose of this study was to investigate the physical
      function over a long time in patients with RA who achieved sustained remission
      (SR) compared with that of patients occasionally achieving remission [non
      sustained remission (NSR)]. METHODS: Patients with RA treated with antitumor
      necrosis factor and included in the South Swedish Arthritis Treatment Group
      register were eligible for this study. We identified patients with a Disease
      Activity Score at 28 joints (DAS28) < 2.6 or Simplified Disease Activity Index
      (SDAI) <= 3.3 at some point and those who achieved SR, i.e., remission during
      consecutive visits for at least 6 months. The course of functional status was
      assessed using the HAQ at each visit. RESULTS: Of the 2416 patients, 1177 (48.7%)
      reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the
      DAS28 and 186 (7.7%) for the SDAI criteria. Comparing the SR and NSR groups, HAQ
      improved during the first 12 months in the DAS28 remission. HAQ continued to
      improve relatively as long as SR was maintained. A higher proportion of patients
      in SR reached full physical function. CONCLUSION: In patients with established
      RA, physical function measured by the HAQ improves in patients reaching SR
      compared with patients who only occasionally reach remission. The improvement
      continues while in remission, which supports that maintaining remission should be
      a treatment goal.

PMID- 27036385
TI  - Increased Frequency of Hand Osteoarthritis in Patients with Primary Sjogren
      Syndrome Compared with Systemic Lupus Erythematosus.
AB  - OBJECTIVE: In daily practice, we noticed that hand osteoarthritis (OA) was
      commonly associated with primary Sjogren syndrome (pSS). Therefore, we aimed to
      investigate its prevalence in patients with pSS in a controlled study. METHODS:
      The study included patients with pSS and controls with systemic lupus
      erythematosus (SLE). Standard hand/wrist radiographs were obtained and classified
      according to the Kellgren-Lawrence system. "Erosive hand OA" was defined
      according to the Verbruggen-Veys classification. RESULTS: There were 114 patients
      with pSS (110 women, 51.0 yrs) and 34 patients with SLE (33 women, 42.4 yrs).
      Among 114 patients with pSS, 42.7% had radiographic, 30.3% symptomatic, and 16.0%
      erosive hand OA. The prevalences of radiographic (45.5%) and erosive hand OA
      (14.4%) in 90 patients with pSS with age- and sex-matched patients with SLE were
      significantly higher than those in patients with SLE (14.7% and 0.0%, p = 0.007
      and p = 0.012, respectively). Interobserver reliabilities for diagnosing
      radiographic and erosive OA were found to be good (K = 0.780 and K = 0.788,
      respectively). Intraobserver reliabilities for diagnosing radiographic and
      erosive OA were also good (K = 0.784 and K = 0.825 for FO, and K = 0.722 and K =
      0.800 for AB, respectively). The frequency of hand OA in patients with pSS was
      found to be increased with increasing age (r = 0.513). The mean age of those with
      erosive hand OA was significantly higher than those without erosive OA (p <
      0.001). CONCLUSION: This study suggests that pSS, conversely to SLE, is more
      frequently associated with hand OA.

PMID- 27036386
TI  - Patients with Gout Treated with Conventional Urate-lowering Therapy: Association
      with Disease Control, Health-related Quality of Life, and Work Productivity.
AB  - OBJECTIVE: Implications of inadequate gout control were assessed through health
      related quality of life (HRQOL) and work productivity of patients with gout
      adequately controlled while taking conventional urate-lowering therapy (ULT) for
      >= 3 months vs those whose gout was inadequately controlled. METHODS:
      Retrospective data were drawn from the Adelphi Disease Specific Programme (DSP),
      a cross-sectional survey of patients with gout in France, Germany, the United
      Kingdom, and the United States. Patients completed these questionnaires: EQ-5D
      (3L), Patient Reported Outcomes Measurement Information System (PROMIS) Health
      Assessment Questionnaire (HAQ), and Work Productivity and Activity Impairment.
      Inadequate control was defined as the most recent serum uric acid (SUA) level > 6
      mg/dl (> 360 umol/l) or >= 2 flares in the last 12 months; adequate control as
      SUA level <= 6 mg/dl (<= 360 umol/l) and 0 flares. Appropriate statistical tests
      were used to assess differences between groups. RESULTS: There were 836 (69%)
      inadequately and 368 (31%) adequately controlled gout cases. Mean age was 61 and
      63 years and duration of current ULT was 32 and 57 months, respectively. Patients
      experiencing inadequate control reported significantly worse functioning and
      HRQOL, as measured by the EQ-5D (0.790 vs 0.877; difference: -0.087; p < 0.001)
      and PROMIS HAQ (13.21 vs 6.91; difference: 6.30; p < 0.001) scales. Productivity
      was also more impaired (work time missed: 4.5% vs 1.3%; impairment while working:
      19.1% vs 5.2%; overall work impairment: 20.4% vs 5.6%; activity impairment: 20.3%
      vs 5.3%; all p < 0.001). CONCLUSION: Less than one-third of patients had gout
      that was adequately controlled. Those experiencing inadequately controlled gout
      reported significantly worse functioning, quality of life, and work productivity.
      Gout treatment strategies to improve disease control may lead to improvements in
      HRQOL and productivity.

PMID- 27036387
TI  - Efficacy and Outcome of Rapid Access Rheumatology Consultation: An Office-based
      Pilot Cohort Study.
AB  - OBJECTIVE: Waiting times for first appointments are a major obstacle to timely
      rheumatology care. To improve access, a cooperative of office-based
      rheumatologists established an immediate access network, offering brief initial
      assessments for patients with musculoskeletal problems. METHODS: Patients were
      assessed at presentation and followed up after 6 months. Data were analyzed
      regarding demographics, diagnostic accuracy, clinical variables such as pain
      levels, and care. RESULTS: There were 335 patients assessed in the 6 cooperating
      practices during dedicated office hours. There were 124 patients (38%) who had a
      symptom duration of < 3 months. For patients with rheumatoid arthritis (RA), this
      proportion was 43% (70% for self-referred patients with RA). In the 325 patients
      available for reassessment after 6 months, initially suspected diagnoses were
      confirmed in 88%. Confirmation rates were 93% for RA (59 patients) and 84% for
      spondyloarthritis (SpA; 46 patients). At the followup examination, the visual
      analog scale for pain in patients with RA had significantly decreased from a
      median (interquartile range) of 70 (57.75-80) to 27.5 (20-42). For patients with
      SpA, the decrease was from 65 (50-79) to 30 (20-40). CONCLUSION: The Rapid Access
      Clinic resulted in a substantial improvement of access to rheumatology
      assessment. More than one-third of the patients presented < 3 months after
      symptom onset. Suspected diagnoses of inflammatory rheumatic diseases were
      confirmed in almost 90%. This initiative demonstrates the feasibility of a rapid
      access service and indicates high diagnostic accuracy in such a setting. In
      particular, with respect to early access, it compares favorably with similar
      hospital-based approaches.

PMID- 27036388
TI  - The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in
      Patients with Giant Cell Arteritis.
AB  - OBJECTIVE: To evaluate the performance of the Birmingham Vasculitis Activity
      Score (BVAS) in the assessment of disease activity in giant cell arteritis (GCA).
      METHODS: Patients with GCA enrolled in a prospective, multicenter, longitudinal
      study with symptoms of active vasculitis during any visit were included.
      Spearman's rank correlation was used to explore the association of the BVAS with
      other measures of disease activity. RESULTS: During a mean (SD) followup of 2.3
      (1.6) years, symptoms of active GCA were present in 236 visits in 136 subjects
      (100 female, 74%). Median (range) BVAS1 (new/worse symptoms) was 1 (0-10) and
      median (range) BVAS2 (persistent symptoms) was 0 (0-5). Median (range)
      physician's global assessment (PGA) was 4 (0-9) for disease activity in the past
      28 days and 2 (0-9) for activity on the day of the visit. Important ischemic
      manifestations of active vasculitis not recorded by the BVAS included tongue/jaw
      claudication (27%), upper extremity claudication (15%), lower extremity
      claudication (5%), carotidynia (7%), and ischemic retinopathy (5%). During 25
      visits (11%) with active disease, all symptoms of active vasculitis were placed
      in the "Other" category yet still resulted in a BVAS1 and BVAS2 of 0. BVAS1
      moderately correlated with PGA for the past 28 days (Spearman's correlation 0.50)
      and physician-rated disease activity for the past 28 days (Spearman's correlation
      0.46). CONCLUSION: The BVAS has limited utility in GCA. Patients with active GCA
      can have a BVAS of 0. Many important ischemic symptoms attributable to active
      vasculitis are not included in the composite score.

PMID- 27036389
TI  - Clinical and Demographic Characteristics of Erosion-free and Erosion-present
      Status in Psoriatic Arthritis in a Cohort Study.
AB  - OBJECTIVE: Psoriatic arthritis (PsA) has been recognized as a severe erosive
      disease. However, some patients do not develop erosions. We aimed to determine
      the prevalence, characteristics, and predictors of erosion-free patients (EFP) as
      compared with erosion-present patients (EPP) among patients with PsA followed
      prospectively. METHODS: This is a retrospective analysis conducted on patients
      from the Toronto PsA cohort. Patients with at least 10 years of followup and
      radiographs were analyzed. Radiographs were scored with the modified Steinbrocker
      method. Baseline (first visit to clinic) characteristics were used to predict the
      development of erosions with logistic regression models. To examine the effect of
      time-varying covariates, Cox regression models were fit for the time to
      development of erosions from baseline. RESULTS: Among 290 patients, 12.4% were
      EFP and 87.6% were EPP over the study period. The mean time to development of
      erosion in the EPP over the course of followup was 6.8 +/- 6.1 years. EFP were
      diagnosed with psoriasis at a younger age compared with EPP. In both models,
      actively inflamed joints and clinically damaged joints were predictive of the
      development of erosion, whereas a longer duration of psoriasis at baseline
      decreased the odds of developing erosion. EPP had a higher percentage of
      unemployment as compared with EFP at baseline and followup visits. CONCLUSION:
      Among patients with PsA followed for at least 10 years, 12.4% never develop
      erosions. The clinical and radiographic findings can ultimately assist in the
      stratification of a patient's prognosis regarding the development of erosions.

PMID- 27036390
TI  - Low-dose Spironolactone: Treatment for Osteoarthritis-related Knee Effusion. A
      Prospective Clinical and Sonographic-based Study.
AB  - OBJECTIVE: To evaluate the effectiveness of spironolactone as a treatment for
      osteoarthritis (OA)-related knee effusion in comparison to ibuprofen, cold
      compresses, and placebo. METHODS: This study was carried out on 200 patients,
      aged 40 years or older, attending the outpatient clinic of the Rheumatology
      Department of Sohag University Hospital with unilateral knee effusion related to
      OA based on clinical examination, musculoskeletal ultrasonography (US), and
      synovial fluid analysis. In group 1, 50 patients received spironolactone 25 mg
      daily for 2 weeks; in group 2, 50 patients took ibuprofen 1200 mg daily for 2
      weeks; in group 3, 50 patients used cold compresses 2 times daily for 2 weeks;
      and in group 4, 50 patients received placebo for the same duration. Fluid > 4 mm
      was considered as effusion. Decrease in fluid to reach below 4-mm thickness was
      considered complete improvement, and any decrease that did not reach below 4 mm
      thickness was considered partial improvement. RESULTS: The mean age of the
      participants was 51.2 +/- 8.1 years. The mean duration of effusion was 16.5 +/-
      3.6 days. In group 1, 66% had complete improvement, 20% partial improvement, and
      14% no response. In group 2, 24% had complete improvement, 12% partial
      improvement, and 64% no response. In group 3, 28% had complete improvement, 14%
      partial improvement, and 58% no response. In group 4, only 6% had complete
      improvement, 10% partial improvement, and 84% no response. CONCLUSION: Low-dose
      spironolactone is a safe and effective medical treatment for OA-related knee
      effusion.

PMID- 27036391
TI  - A recurrent epidermoid cyst of the spleen: report of a case and literature
      review.
AB  - BACKGROUND: Splenic cysts are rare disease. Epidermoid cysts of the spleen belong
      to the primary nonparasitic splenic cysts group. They are an unusual event in
      surgical practice. Usually, epidermoid cysts occur in children and young female.
      Most often, they are asymptomatic, but they may present with abdominal
      discomfort. CASE PRESENTATION: We are reporting a rare case of a 23-year-old
      female came to our attention with history of intermittent pain and previously
      undergone two times to laparoscopic decapsulation of the cyst in others
      institutions. During hospitalization, serum and intracystic levels of tumor
      marker CA19-9 increased. Enhanced CT of the abdomen showed recurrent large cyst
      in the upper pole of the spleen with satellite nodules. Laparotomic total
      splenectomy was performed. Histopathological and immunoreactive examinations were
      executed, and they revealed stratified squamous epithelium on the inner surface
      of cystic wall, which was positive for EMA, CEA, and CA19-9. The diagnosis of
      epidermoid cyst was confirmed. CONCLUSIONS: Recently, the surgical approach is
      changing towards conservative treatments in order to save the spleen in young
      patients for immunological reasons. Sometimes, this target is not achievable. In
      such circumstances, like recurrent large cyst, anomalous anatomical relationship
      to the surrounding tissues, total splenectomy is safe and necessary.

PMID- 27036392
TI  - Effects of MIAVS on Early Postoperative ELWI and Respiratory Mechanics.
AB  - BACKGROUND: The effects of minimally invasive aortic valve surgery (MIAVS) on the
      early postoperative extravascular lung water index (ELWI) and respiratory
      mechanics have rarely been studied. MATERIAL/METHODS: A total of 90 patients were
      divided into 3 groups: a conventional full sternotomy (CS) group (n=30), an upper
      ministernotomy (US) group (n=30), and a right anterior thoracotomy (RT) group
      (n=30). Hemodynamic and respiratory mechanics parameters were recorded at
      perioperative time points, including before skin incision (T(-1)); at sternum
      closing (T0); and 4 h (T4), 8 h (T8), 12 h (T12), and 24 h (T24) after the
      operation. The ventilator support time, ICU length of stay, and postoperative
      hospitalization time, as well as the thoracic drainage volume and blood
      transfusion volume, were recorded. RESULTS: The ELWI and pulmonary vascular
      permeability index (PVPI) increased at T4, and the values were significantly
      lower in the US group than in the RT group and CS group (P<0.05). At T8, the ELWI
      and PVPI in the US group and RT group were significantly lower than in the CS
      group. At T12, there were no significant differences among the 3 groups. In
      addition, at T4 static lung compliance decreased, plateau airway pressure
      increased, and airway resistance changed non-significantly. There were no
      significant differences between the US group and the RT group, but both groups
      showed better results than the CS group did. CONCLUSIONS: The ELWI and PVPI may
      transiently increase after aortic valve surgery with cardiopulmonary bypass.
      Compared with the 12 h required to recover from a conventional sternotomy
      operation, it may only take 8 h to recover from MIAVS.

PMID- 27036393
TI  - Double Trouble: The Diagnostic Dilemma of Diffuse Alveolar Hemorrhage.

PMID- 27036394
TI  - Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and
      Insulin Values in AIM-HIGH.
AB  - BACKGROUND: Niacin is an antidyslipidemic agent that may cause blood sugar
      elevation in patients with diabetes, but its effects on glucose and insulin
      values in nondiabetic statin-treated subjects with cardiovascular disease and at
      high risk for diabetes are less well known. METHODS: This was a prespecified,
      intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic
      syndrome with low high-density lipoprotein/high triglycerides: Impact on Global
      Health outcomes trial which randomized 3,414 participants at 92 centers in the US
      and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or
      simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose
      and insulin values were measured. Those experiencing an adverse event indicative
      of diabetes or starting medications for diabetes were considered to have
      confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up
      glucose measurements were categorized into normal, impaired fasting glucose or
      newly diagnosed diabetes (presumed or confirmed) states. RESULTS: Compared with
      placebo, ERN increased annual fasting glucose from baseline to 1 year in both
      those with normal (7.9 +/- 15.8 vs 4.3 +/- 10.3 mg/dL; P < .001) and impaired
      fasting glucose (4.1 +/- 18.7 vs 1.4 +/- 14.9; P < .02) and increased insulin
      levels. Both effects waned over the next 2 years. There were less consistent
      effects in those with baseline diabetes. There was an increased risk of
      progressing from normal to presumed or confirmed impaired fasting glucose (ERN
      197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but
      no difference in diabetes development in the 2 treatment groups except in those
      with normal fasting glucose at baseline. CONCLUSIONS: The addition of ERN to
      simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at
      baseline, and there was a trend toward increased development of new-onset
      diabetes. In addition, ERN increased the risk of developing impaired fasting
      glucose, which may have deleterious consequences over time and warrants further
      study.

PMID- 27036395
TI  - Pebble-like lesions: A rare sight in the bronchial tree.

PMID- 27036396
TI  - Reply.

PMID- 27036397
TI  - Modified gold nanoparticles for intracellular delivery of anti-liver cancer
      siRNA.
AB  - To overcome the rapid enzymatic degradation and low transfection efficiency of
      siRNA, the delivery carriers for siRNA is a therapeutic demand to increase its
      stability. Gold nanoparticles (AuNPs) modified by branched polyethyleneimine
      (bPEI) were developed as an efficient and safe intracellular delivery carriers
      for siRNA. The current study implied that siRNA designed against an oncogene c
      Myc could be delivered by a modified AuNPs complex without significant
      cytotoxicity. The comparative semi-quantitative and quantitative real time PCR
      were used to measure the c-Myc gene expression after transfection with naked
      siRNA and siRNA/bPEI/AuNPs, but AuNPs interfered with PCR. However, the c-Myc
      protein translation was successfully detected in the transfected HuH7 cells with
      naked siRNA and siRNA/bPEI/AuNPs and it was found to be inhibited by
      siRNA/bPEI/AuNPs more than naked siRNA. The results validate the successful
      silencing of c-Myc gene. Accordingly, it may confirm the promising and effective
      delivery of siRNA by bPEI/AuNPs. The complex enhances the cellular uptake of
      siRNA without significant cytotoxicity and confirms that bPEI modified AuNPs
      could be used as a good candidate for safe cellular delivery of siRNA. 

PMID- 27036398
TI  - Planar cell polarity gene expression correlates with tumor cell viability and
      prognostic outcome in neuroblastoma.
AB  - BACKGROUND: The non-canonical Wnt/Planar cell polarity (PCP) signaling pathway is
      a major player in cell migration during embryonal development and has recently
      been implicated in tumorigenesis. METHODS: Transfections with cDNA plasmids or
      siRNA were used to increase and suppress Prickle1 and Vangl2 expression in
      neuroblastoma cells and in non-tumorigenic cells. Cell viability was measured by
      trypan blue exclusion and protein expression was determined with western
      blotting. Transcriptional activity was studied with luciferase reporter assay and
      mRNA expression with real-time RT-PCR. Immunofluorescence stainings were used to
      study the effects of Vangl2 overexpression in non-tumorigenic embryonic cells.
      Statistical significance was tested with t-test or one-way ANOVA. RESULTS: Here
      we show that high expression of the PCP core genes Prickle1 and Vangl2 is
      associated with low-risk neuroblastoma, suppression of neuroblastoma cell growth
      and decreased Wnt/beta-catenin signaling. Inhibition of Rho-associated kinases
      (ROCKs) that are important in mediating non-canonical Wnt signaling resulted in
      increased expression of Prickle1 and inhibition of beta-catenin activity in
      neuroblastoma cells. In contrast, overexpression of Vangl2 in MYC immortalized
      neural stem cells induced accumulation of active beta-catenin and decreased the
      neural differentiation marker Tuj1. Similarly, genetically modified mice with
      forced overexpression of Vangl2 in nestin-positive cells showed decreased Tuj1
      differentiation marker during embryonal development. CONCLUSIONS: Our
      experimental data demonstrate that high expression of Prickle1 and Vangl2 reduce
      the growth of neuroblastoma cells and indicate different roles of PCP proteins in
      tumorigenic cells compared to normal cells. These results suggest that the
      activity of the non-canonical Wnt/PCP signaling pathway is important for
      neuroblastoma development and that manipulation of the Wnt/PCP pathway provides a
      possible therapy for neuroblastoma.

PMID- 27036399
TI  - A Portable Diode Array Spectrophotometer.
AB  - A cheap portable visible light spectrometer is presented. The spectrometer uses
      readily sourced items and could be constructed by anyone with a knowledge of
      electronics. The spectrometer covers the wavelength range 450-725 nm with a
      resolution better than 5 nm. The spectrometer uses a diffraction grating to
      separate wavelengths, which are detected using a 128-element diode array, the
      output of which is analyzed using a microprocessor. The spectrum is displayed on
      a small liquid crystal display screen and can be saved to a micro SD card for
      later analysis. Battery life (2 * AAA) is estimated to be 200 hours. The overall
      dimensions of the unit are 120 * 65 * 60 mm, and it weighs about 200 g.

PMID- 27036400
TI  - Letter to the editor: Comparing pace and speed in the pulmonary circulation?

PMID- 27036402
TI  - Corrigendum.

PMID- 27036401
TI  - Reply to: "Letter to the editor: Comparing pace and speed in the pulmonary
      circulation?".

PMID- 27036403
TI  - Central venous catheter infection-related glomerulonephritis under long-term
      parenteral nutrition: a report of two cases.
AB  - BACKGROUND: Advances in long-term parenteral nutrition via indwelling central
      venous catheter have improved the quality of life and mortality in patients with
      life-threatening gastrointestinal diseases complicated with severely impaired
      absorption. However, infection to central venous catheter is still a common and
      critical complication for such patients. We encountered two patients under long
      term parenteral nutrition who developed glomerulonephritis associated with
      central venous catheter infection. Persistent bacterial infection in indwelling
      medical devices placed in the blood-stream such as a ventricular-atrial shunt is
      known to cause glomerulonephritis, a condition termed shunt nephritis. We
      reported the clinical manifestations, treatment and their pathological findings
      in the two patients with glomerulonephritis associated with central venous
      catheter infection. CASE PRESENTATION: Both patients suffered from megacystis
      microcolon intestinal hypoperistalsis syndrome, a form of pseudo-Hirschsprung's
      disease. They had been receiving home parenteral nutrition via central venous
      catheter because of severe malabsorption. They presented proteinuria, hematuria,
      hypocomplementemia and positive PR3-antineutrophilic cytoplasmic antibody
      accompanied by Staphylococcus epidermidis infection in the central venous
      catheter. Their renal biopsy revealed membranoproliferative glomerulonephritis
      with positive C3 deposition. One of them recovered completely following the
      removal of catheter and administration of antibiotics, while another did not
      respond to the treatments. We then treated her with methylprednisolone pulse
      therapy followed by prednisolone. She responded well, and achieved complete
      remission. CONCLUSION: As central venous catheter infection-related
      glomerulonephritis has a similar etiology to shunt nephritis, removal of the
      catheter and administration of antibiotics is fundamental to the treatment. If a
      patient is resistant to such conventional therapy, additional steroid and/or
      immunosuppressive agent could be considered. Although the number of patients with
      classical shunt nephritis is decreasing since the ventricular-peritoneal shunt
      has become became the major procedure for hydrocephalus, central venous catheter
      infection-related glomerulonephritis may increase in the future due to a marked
      increase in the number of patients receiving long-term parenteral nutrition.
      Routine urinalysis should be considered in such patients for early detection of
      central venous catheter infection-related glomerulonephritis.

PMID- 27036404
TI  - Dietary beta-glucan improved growth performance, Vibrio counts, haematological
      parameters and stress resistance of pompano fish, Trachinotus ovatus Linnaeus,
      1758.
AB  - This study evaluated effects of graded levels of dietary beta-glucan (0, 0.5, 1,
      2 and 4 g kg(-1)) on growth performance, haematological parameters, intestinal
      Vibrio counts, dose requirement and salinity stress resistance in pompano fish
      Trachinotus ovatus (6.45 g +/- 0.06 (SEM)). After 8-weeks of diet feeding, growth
      was significantly higher in fish fed diets with 0.10% beta-glucan compared to
      fish fed control diet (no beta-glucan). Survival increased significantly in fish
      fed 0.05 and 0.10% beta-glucan compared to control diet. There were significant
      increases in red blood cells (in 0.20% beta-glucan diet), in total leukocytes (in
      0.05-0.20% beta-glucan diet), in both lymphocyte and monocyte count in fish fed
      0.10%-0.40% beta-glucan diet. However, dietary beta-glucan did not affect
      neutrophil, eosinophil and basophil counts. Intestinal Vibrio counts were reduced
      in fish fed any level of beta-glucan compared to control. In addition, dietary
      beta-glucan levels highly correlated with growth, survival, intestinal Vibrio
      counts and haematological index. Optimal beta-glucan levels for maximal growth of
      fish were predicted to be 0.122% at day 21 (R(2) = 98.53%), 0.120% at day 28
      (R(2) = 78.55%), 0.115% at day 42 (R(2) = 62.21%) and 0.090% at day 56 (R(2) =
      75.18%), showing a decreasing beta-glucan requirement with increasing fish size.
      Furthermore, optimal beta-glucan levels for maximal haematological parameters
      based on lymphocyte count, was estimated to be 0.120% (R(2) = 98.53%) at day 56.
      Also, fish fed 0.05%-0.20% beta-glucan showed better resistance against salinity
      stress. In conclusion, beta-glucan supplementation is effective for improving
      growth, intestinal Vibrio counts and boosted stress resistance of the pompano
      fish, T. ovatus. 

PMID- 27036405
TI  - Cloning, identification and functional analysis of a beta-catenin homologue from
      Pacific white shrimp, Litopenaeus vannamei.
AB  - Wnt signaling is known to control multiple of cellular processes such as cell
      differentiation, communication, apoptosis and proliferation, and is also reported
      to play a role during microbial infection. beta-catenin is a key regulator of the
      Wnt signaling cascade. In the present study, we cloned and identified a beta
      catenin homologue from Litopenaeus vannamei termed Lvbeta-catenin. The full
      length of Lvbeta-catenin transcript was 2797 bp in length within a 2451 bp open
      reading frame (ORF) that encoded a protein of 816 amino acids. Lvbeta-catenin
      protein was comprised of several characteristic domains such as an N-terminal
      region of GSK-beta consensus phosphorylation site and Coed coil section, a
      central region of 12 continuous Armadillo/beta-Catenin-like repeat (ARM) domains
      and a C-terminal region. Real-time PCR showed Lvbeta-catenin expression was
      responsive to Vibrio parahaemolyticus and white spot syndrome virus (WSSV)
      infection. Dual-reporter analysis showed that over-expression of Lvbeta-catenin
      could induce activation of the promoter activities of several antimicrobial
      peptides (AMPs) such as shrimp PEN4, suggesting that Lvbeta-catenin could play a
      role in regulating the production of AMPs. Knockdown of Lvbeta-catenin enhanced
      the sensitivity of shrimps to V. parahaemolyticus and WSSV challenge, suggesting
      Lvbeta-catenin could play a positive role against bacterial and viral pathogens.
      In summary, the results presented in this study provided some insights into the
      function of Wnt/beta-catenin of shrimp in regulating AMPs and the host defense
      against invading pathogens. 

PMID- 27036406
TI  - Neuroactivity of detonation nanodiamonds: dose-dependent changes in transporter
      mediated uptake and ambient level of excitatory/inhibitory neurotransmitters in
      brain nerve terminals.
AB  - BACKGROUND: Nanodiamonds are one of the most perspective nano-sized particles
      with superb physical and chemical properties, which are mainly composed of carbon
      sp(3) structures in the core with sp(2) and disorder/defect carbons on the
      surface. The research team recently demonstrated neuromodulatory properties of
      carbon nanodots with other than nanodiamonds hybridization types, i.e., sp(2)
      hybridized graphene islands and diamond-like sp(3) hybridized elements. RESULTS:
      In this study, neuroactive properties of uncoated nanodiamonds produced by
      detonation synthesis were assessed basing on their effects on transporter
      mediated uptake and the ambient level of excitatory and inhibitory
      neurotransmitters, glutamate and gamma-aminobutyric acid (GABA), in isolated rat
      brain nerve terminals. It was shown that nanodiamonds in a dose-dependent manner
      attenuated the initial velocity of Na(+)-dependent transporter-mediated uptake
      and accumulation of L-[(14)C]glutamate and [(3)H]GABA by nerve terminals and
      increased the ambient level of these neurotransmitters. Also, nanodiamonds caused
      a weak reduction in acidification of synaptic vesicles and depolarization of the
      plasma membrane of nerve terminals. CONCLUSIONS: Therefore, despite different
      types of hybridization in nanodiamonds and carbon dots, they exhibit very similar
      effects on glutamate and GABA transport in nerve terminals and this common
      feature of both nanoparticles is presumably associated with their nanoscale size.
      Observed neuroactive properties of pure nanodiamonds can be used in
      neurotheranostics for simultaneous labeling/visualization of nerve terminals and
      modulation of key processes of glutamate- and GABAergic neurotransmission. In
      comparison with carbon dots, wider medical application involving
      hypo/hyperthermia, external magnetic fields, and radiolabel techniques can be
      perspective for nanodiamonds.

PMID- 27036407
TI  - Provider Screening and Counseling for Intimate Partner Violence: A Systematic
      Review of Practices and Influencing Factors.
AB  - BACKGROUND: Primary care providers have an important role in identifying
      survivors of intimate partner violence (IPV) and providing safety options.
      Routine screening rates by providers have been consistently low, indicating a
      need to better understand providers' practices to ensure the translation of
      policy into clinical practice. AIM: This systematic review examines common themes
      regarding provider screening practices and influencing factors on these
      practices. METHOD: A literature search was conducted using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search
      focused on research articles which met the following criteria: (1) health-care
      providers as participants, (2) provider reports on screening and counseling
      practices for IPV, and (3) were in English or Spanish. RESULTS: A total of 35
      studies were included in the review. Across studies, providers commonly
      acknowledged the importance of IPV screening yet often used only selective
      screening. Influencing factors on clinic, provider, and patient levels shaped the
      process and outcomes of provider screening practices. Overall, a great deal of
      variability exists in regard to provider screening practices. This variability
      may be due to a lack of clear system-level guidance for these practices and a
      lack of research regarding best practices. CONCLUSIONS: These findings suggest
      the necessity of more facilitative, clearly defined, and perhaps mandatory
      strategies to fulfill policy requirements. Future research directions are
      outlined to assist with these goals.

PMID- 27036408
TI  - Study protocol for a web-based personalized normative feedback alcohol
      intervention for young adult veterans.
AB  - BACKGROUND: Young adult veterans from the wars in Iraq and Afghanistan represent
      a population at-risk for heavy and problematic alcohol use. Unfortunately, few
      seek treatment for alcohol concerns and those that do seek care may drop out from
      lengthy multicomponent treatments. Additionally, veterans who live in rural areas
      and those who are not engaged in the Veterans Affairs Healthcare System are often
      overlooked, difficult to engage in treatment, and may not be actively seeking
      treatment for heavy patterns of use that may develop into an alcohol use
      disorder. The objective of this proposed randomized controlled trial is to
      develop and pilot test a brief, stand-alone Internet-based alcohol intervention
      with young adult veterans to help them reduce their drinking and prevent the
      development of problematic alcohol use. METHODS/DESIGN: Recruitment and
      intervention is delivered entirely over the Internet to address barriers to
      seeking care among this at-risk group. The online intervention consists of an
      assessment followed by a single module of personalized normative feedback (PNF),
      which provides individuals with accurate information to reduce misperceptions
      regarding the frequency and acceptability of risky peer behavior. PNF has
      established efficacy as included within multicomponent interventions targeting
      military populations or as a stand-alone intervention with young adult college
      students, but has not yet been empirically supported for the at-risk veteran
      population. This paper describes the development of the PNF intervention content
      and details the protocol for the intervention study, which will utilize a sample
      of 600 young adult veterans to examine the efficacy of the brief PNF intervention
      targeted toward reducing perceived norms, intentions to drink, actual drinking
      behavior, and consequences. Specific subpopulations of this veteran population,
      including those with mental health concerns and those differentiated by level of
      drinking problems, reasons for drinking, and connection to peers, will be
      examined to support generalizability of the intervention. DISCUSSION: This
      intervention has the potential to improve veteran health care by utilizing a
      novel approach to increase access to care, assist with drinking reductions, and
      prevent alcohol-related problems. Trial registration ClinicalTrials.gov
      Identifier NCT02187887.

PMID- 27036409
TI  - A qualitative evaluation of the impact of a palliative care course on
      preregistration nursing students' practice in Cameroon.
AB  - BACKGROUND: Current evidence suggests that palliative care education can improve
      preregistration nursing students' competencies in palliative care. However, it is
      not known whether these competencies are translated into students' practice in
      the care of patients who are approaching the end of life. This paper seeks to
      contribute to the palliative care evidence base by examining how nursing students
      in receipt of education report transfer of learning to practice, and what the
      barriers and facilitators may be, in a resource-poor country. METHODS: We
      utilised focus groups and individual critical incident interviews to explore
      nursing students' palliative care learning transfer. Three focus groups,
      consisting of 23 participants and 10 individual critical incident interviews were
      conducted with preregistration nursing student who had attended a palliative care
      course in Cameroon and had experience caring for a patient approaching the end of
      life. Data was analysed thematically, using the framework approach. RESULTS: The
      results suggest that nursing students in receipt of palliative care education can
      transfer their learning to practice. Students reported recognizing patients with
      palliative care needs, providing patients with physical, psychosocial and
      spiritual support and communicating patient information to the wider care team.
      They did however perceive some barriers to this transfer which were either
      related to themselves, qualified nurses, the practice setting or family
      caregivers and patients. CONCLUSION: The findings from this study suggest that
      nursing student in receipt of palliative care education can use their learning in
      practice to provide care to patients and their families approaching the end of
      life. Nevertheless, these findings need to be treated with some caution given the
      self-reported nature of the data. Demonstrating the link between preregistration
      palliative care education and patient care is vital to ensuring that newly
      acquired knowledge and skills are translated and embedded into clinical practice.
      This study also has implications for advocating for palliative care policies and
      adequately preparing clinical placement sites for students' learning and transfer
      of learning.

PMID- 27036410
TI  - Cortisol fluctuations relate to interictal epileptiform discharges in stress
      sensitive epilepsy.
AB  - People with epilepsy often report seizures precipitated by stress. This is
      believed to be due to effects of stress hormones, such as cortisol, on neuronal
      excitability. Cortisol, regardless of stress, is released in hourly pulses, whose
      effect on epileptic activity is unknown. We tested the relation between cortisol
      levels and the incidence of epileptiform abnormalities in the
      electroencephalogram of people with focal epilepsy. Morning cortisol levels were
      measured in saliva samples obtained every 15 min. Interictal epileptiform
      discharges were determined in the same time periods. We investigated the
      relationship between cortisol levels and the epileptiform discharges
      distinguishing persons with from those without stress-precipitated seizures
      (linear mixed model), and analysed the contribution of individual, epilepsy and
      recording characteristics with multivariable analysis. Twenty-nine recordings
      were performed in 21 individuals. Cortisol was positively related to incidence of
      epileptiform discharges (beta = 0.26, P = 0.002) in people reporting stress
      sensitive seizures, but not those who did not report stress sensitivity (beta = 
      0.07, P = 0.64). The relationship between cortisol and epileptiform discharges
      was positively associated only with stress sensitivity of seizures (beta = 0.31,
      P = 0.005). The relationship between cortisol levels and incidence of interictal
      epileptiform discharges in people with stress-sensitive seizures suggests that
      stress hormones influence disease activity in epilepsy, also under basal
      conditions.

PMID- 27036412
TI  - Rifampicin-containing combinations are superior to combinations of vancomycin,
      linezolid and daptomycin against Staphylococcus aureus biofilm infection in vivo
      and in vitro.
AB  - Susceptibility to antibiotics is dramatically reduced when bacteria form
      biofilms. In clinical settings this has a profound impact on treatment of implant
      associated infections, as these are characterized by biofilm formation. Current
      routine susceptibility testing of microorganisms from infected implants does not
      reflect the actual susceptibility, and the optimal antibiotic strategy for
      treating implant-associated infections is not established. In this study of
      biofilm formation in implant-associated osteomyelitis, we compared thein
      vitroandin vivoefficacy of selected antibiotics alone and in combination
      againstStaphylococcus aureus.We tested vancomycin, linezolid, daptomycin and
      tigecycline alone and in combination with rifampicin, vancomycin, linezolid and
      daptomycin againstS. aureusIn vitro, biofilm formation dramatically reduced
      susceptibility by a factor of 500-2000.In vivo, antibiotic combinations were
      tested in a murine model of implant-associated osteomyelitis. Mice were infected
      by inserting implants colonized withS. aureustrough their tibia. After 11 days,
      the animals were divided into different groups (five animals/group) and given 14
      days of antibiotic therapy. All antibiotics resulted in a reduced bacterial load
      in the infected bone surrounding the implant. Overall, the most effective
      antibiotic combinations contained rifampicin. Combinations containing two non
      rifampicin antibiotics were not more active than single drugs. 

PMID- 27036411
TI  - Association of Urinary Phthalate Metabolites With Erectile Dysfunction in Racial
      and Ethnic Groups in the National Health and Nutrition Examination Survey 2001
      2004.
AB  - Phthalates are endocrine-disrupting compounds detectable in more than 75% of the
      U.S. population with differential distributions across racial and ethnic groups,
      and they have been linked with reduced levels of serum testosterone. This study
      aims to investigate the associations of phthalate metabolites with erectile
      dysfunction (ED) and to determine whether these associations vary by
      race/ethnicity among men in the United States. Analyzed data for 12 phthalate
      metabolites from 3,746 men (>=20 years old), who participated in the National
      Health and Nutrition Examination Survey 2001-2004 cross-sectional study, were
      included. Metabolites included MBP, MCHP, MEP, MEHP, MiNP, MBzP, MMP, MCPP,
      MEHHP, MEOHP, MiBP, and MECPP. Racial/ethnic groups included non-Hispanic Blacks
      ( n = 770), non-Hispanic Whites ( n = 2,147), and Mexican Americans ( n = 829).
      ED was assessed by a single question during a self-paced, computer-assisted self
      interview. In racial/ethnic stratified analyses, there were higher MBP and MBzP
      concentrations that had a strong-dose response association with lower prevalence
      odds of ED among Mexican Americans, ptrend < .01, and ptrend = .03, respectively.
      Similarly, a significant inverse association between MEHHP and likelihood of ED
      among non-Hispanic Black men ( ptrend < .04) was observed. Furthermore,
      significant inverse associations between higher concentrations of phthalates and
      ED were identified only in minority populations. Further investigations,
      particularly prospective studies, are warranted to determine the role of
      phthalates on the biological mechanism(s) associated with ED. A focus may be
      placed on testosterone levels which are suggested to be affected by phthalates,
      and also low levels of testosterone are suggested to increase the risk of ED.

PMID- 27036413
TI  - Faculty Communication Knowledge, Attitudes, and Skills Around Chronic Non
      Malignant Pain Improve with Online Training.
AB  - OBJECTIVE: Many physicians struggle to communicate with patients with chronic,
      non-malignant pain (CNMP). Through the use of a Web module, the authors aimed to
      improve faculty participants' communication skills knowledge and confidence, use
      of skills in clinical practice, and actual communication skills. SUBJECTS: The
      module was implemented for faculty development among clinician-educators with
      university faculty appointments, outpatient clinical practices, and teaching
      roles. METHODS: Participants completed the Collaborative Opioid Prescribing
      Education Risk Evaluation and Mitigation Strategy (COPE-REMS(r)) module, a free
      Web module designed to improve provider communication around opioid prescribing.
      Main study outcomes were improvements in CNMP communication knowledge, attitudes,
      and skills. Skills were assessed by comparing a subset of participants' Observed
      Structured Clinical Exam (OSCE) performance before and after the curriculum.
      RESULTS: Sixty-two percent of eligible participants completed the curriculum in
      2013. Knowledge-based test scores improved with curriculum completion (75% vs.
      90%; P < 0.001). Using a 5-point Likert-type scale, participants reported
      improved comfort in managing patients with CNMP both immediately post-curriculum
      and at 6 months (3.6 pre vs. 4.0 post vs. 4.1 at 6 months; P = 0.02), as well as
      improvements in prescribing opioids (3.3 vs. 3.8 vs. 3.9, P = 0.01) and
      conducting conversations about discontinuing opioids (2.8 vs. 3.5 vs. 3.9, P <
      0.001). Additionally, CNMP-specific communication skills on the OSCE improved
      after the curriculum (mean 67% vs. 79%, P = 0.03). CONCLUSIONS: Experienced
      clinician-educators improved their communication knowledge, attitudes, and skills
      in managing patients with CNMP after implementation of this curriculum. The
      improvements in attitudes were sustained at six months. A Web-based curriculum
      such as COPE-REMS(r) may be useful for other programs seeking improvement in
      faculty communication with patients who have CNMP.

PMID- 27036414
TI  - Altered molecular expression of TLR-signaling pathways affects the steady-state
      release of IL-12p70 and IFN-alpha in patients with relapsing-remitting multiple
      sclerosis.
AB  - Recent evidence suggests a key role of dendritic cells (DC) in the
      immunopathogenesis of multiple sclerosis (MS). Whereas dysfunction of DC was
      reported in MS patients, the underlying cause for this is not fully elucidated
      yet. The aim of the present study was to compare the gene expression profile of
      molecules involved in TLR4 and TLR7 signaling in DC from patients with MS and
      healthy controls. For this, circulating DC subsets were purified from patients
      with relapsing-remitting MS (RRMS) and from healthy controls for quantitative
      real-time PCR analysis. Additionally, TLR responsiveness in peripheral blood was
      investigated. We observed an aberrant steady-state release of IL-12p70 and IFN
      alpha in patients with RRMS compared with healthy controls. Expression of IRF1
      and JUN was reduced in conventional DC from patients with RRMS. In plasmacytoid
      DC from patients with RRMS, expression of IRF7 and IFNGR1 was reduced, while
      higher expression levels of TLR4 and LY86 were found compared with DC from
      healthy controls. The observed alterations in the gene expression of molecules
      involved in the TLR4 and TLR7 signaling pathways in circulating DC subsets may
      underlie the impaired IL-12p70 and IFN-alpha secretion in patients with RRMS,
      thereby potentially contributing to the disease pathogenesis of MS.

PMID- 27036415
TI  - Pay for performance in Nigeria: the influence of context and implementation on
      results.
AB  - Pay-for-performance (P4P) has recently been introduced in Nigeria to improve
      quality of health services. Its early results show significant variation between
      implementation sites. Literature suggests this might be explained by differences
      in design, context and implementation of the scheme. This study aimed to explore
      how context and implementation influence P4P in Nigeria. Semi-structured in-depth
      interviews with 36 health workers explored their views and experiences on how
      contextual and implementation factors influenced the impact of the P4P scheme.
      Data were analysed using the framework approach. Four themes captured the views
      and experiences of participants. Uncertainty of earning the incentive and
      inadequate infrastructure reduced health worker motivation and performance
      results; whilst adequate health worker understanding of the scheme and good
      managerial skills (health facility level) improved motivation and performance.
      Minimising delays in incentive payments, effective communication and improving
      the health workers understanding of the P4P scheme are likely to improve the
      outcomes of pay for performance programmes, independent of their design. 

PMID- 27036416
TI  - Sphingosine-1-phosphate receptor inhibition prevents denervation-induced
      dendritic atrophy.
AB  - A hallmark of several major neurological diseases is neuronal cell death. In
      addition to this primary pathology, secondary injury is seen in connected brain
      regions in which neurons not directly affected by the disease are denervated.
      These transneuronal effects on the network contribute considerably to the
      clinical symptoms. Since denervated neurons are viable, they are attractive
      targets for intervention. Therefore, we studied the role of Sphingosine-1
      phosphate (S1P)-receptor signaling, the target of Fingolimod (FTY720), in
      denervation-induced dendritic atrophy. The entorhinal denervation in vitro model
      was used to assess dendritic changes of denervated mouse dentate granule cells.
      Live-cell microscopy of GFP-expressing granule cells in organotypic entorhino
      hippocampal slice cultures was employed to follow individual dendritic segments
      for up to 6 weeks after deafferentation. A set of slice cultures was treated with
      FTY720 or the S1P-receptor (S1PR) antagonist VPC23019. Lesion-induced changes in
      S1P (mass spectrometry) and S1PR-mRNA levels (laser microdissection and qPCR)
      were determined. Denervation caused profound changes in dendritic stability.
      Dendritic elongation and retraction events were markedly increased, resulting in
      a net reduction of total dendritic length (TDL) during the first 2 weeks after
      denervation, followed by a gradual recovery in TDL. These changes were
      accompanied by an increase in S1P and S1PR1- and S1PR3-mRNA levels, and were not
      observed in slice cultures treated with FTY720 or VPC23019. We conclude that
      inhibition of S1PR signaling prevents dendritic destabilization and denervation
      induced dendrite loss. These results suggest a novel neuroprotective effect for
      pharmaceuticals targeting neural S1PR pathways. 

PMID- 27036418
TI  - Communication: Multiple-property-based diabatization for open-shell van der Waals
      molecules.
AB  - We derive a new multiple-property-based diabatization algorithm. The
      transformation between adiabatic and diabatic representations is determined by
      requiring a set of properties in both representations to be related by a
      similarity transformation. This set of properties is determined in the adiabatic
      representation by rigorous electronic structure calculations. In the diabatic
      representation, the same properties are determined using model diabatic states
      defined as products of undistorted monomer wave functions. This diabatic model is
      generally applicable to van der Waals molecules in arbitrary electronic states.
      Application to locating seams of conical intersections and collisional transfer
      of electronic excitation energy is demonstrated for O2 - O2 in low-lying excited
      states. Property-based diabatization for this test system included all components
      of the electric quadrupole tensor, orbital angular momentum, and spin-orbit
      coupling. 

PMID- 27036417
TI  - Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and
      PH2 perturb vacuolar physiology.
AB  - BACKGROUND: Recent work has perfected yeast-based methods for measuring drug
      transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter
      (PfCRT). METHODS: The approach relies on inducible heterologous expression of
      PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug
      concentrations are not toxic to the yeast, nor is expression of PfCRT alone
      toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast
      impaired, due to inward transport of chloroquine (CQ) via the transporter.
      RESULTS: During analysis of all 53 known naturally occurring PfCRT isoforms, two
      isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even
      in the absence of CQ. Additional analysis of six very recently identified PfCRT
      isoforms from Malaysia also showed some toxicity. In this paper the nature of
      this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of
      PfCRT transport CQ with an efficiency intermediate to that catalyzed by
      previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is
      found to perturb vacuolar physiology, suggesting a fitness cost to position 160
      amino acid substitutions. CONCLUSION: These data further define the wide range of
      activities that exist for PfCRT isoforms found in P. falciparum isolates from
      around the globe.

PMID- 27036419
TI  - Communication: Nanoscale structure of tetradecyltrihexylphosphonium based ionic
      liquids.
AB  - In a recent communication [J. J. Hettige et al., J. Chem. Phys. 140, 111102
      (2014)], we investigated the anomalous temperature dependence of the X-ray first
      sharp diffraction peak (or prepeak) in the tetradecyltrihexylphosphonium
      bis(trifluoromethylsulfonyl)-amide ionic liquid. Contrary to what was expected
      and often observed, the first sharp diffraction peak in this system was shown to
      increase in intensity with increasing temperature. This implies higher
      intermediate-range periodicity at a higher temperature. Is this counter-intuitive
      behavior specific to the combination of cation and anion? The current work
      analyzes the structural behavior of the same cation coupled with six different
      anions ranging from the small and spherically symmetric Cl(-) to the more
      structurally complex and charge-diffuse NTf2 (-). In all cases, the same
      temperature behavior trend for the prepeak is observed independent of anionic
      nature. We will show that the intensity increase in the prepeak region is
      associated with the structural behavior of charged liquid subcomponents. Instead,
      upon a temperature increase, the apolar subcomponents contribute to what would be
      an expected decrease of prepeak intensity. 

PMID- 27036420
TI  - Communication: Infrared spectroscopy of salt-water complexes.
AB  - To explore how the ion-pair in a single salt molecule evolves with the addition
      of water, infrared (IR) spectra of complexes composed of NaCl and multiple water
      molecules have been recorded for the first time. The NaCl(H2O)n complexes were
      formed and probed in liquid helium nanodroplets, and IR spectra were recorded for
      n = 1 -> 4. The spectra for n = 1, 2, and 3 are consistent with formation of the
      lowest energy contact-ion pair structures in which each water molecule forms a
      single ionic hydrogen bond to an intact Na(+)Cl(-) ion-pair. Alternative
      structures with hydrogen bonding between water molecules become energetically
      competitive for n = 4, and the IR spectrum indicates likely the coexistence of at
      least two isomers. 

PMID- 27036421
TI  - Relativistic theory of the Jahn-Teller effect: p-orbitals in tetrahedral and
      trigonal systems.
AB  - A relativistic generalization of Jahn-Teller theory is presented which includes
      spin-orbit coupling effects beyond low-order Taylor expansions in vibrational
      coordinates. For the example of a p-electron in tetrahedral and trigonal
      environments, the matrix elements of the Breit-Pauli spin-orbit-coupling operator
      are expressed in terms of the matrix elements of the electrostatic electronic
      potential. Employing expansions of the latter in invariant polynomials in
      symmetry-adapted nuclear coordinates, the spin-orbit induced Jahn-Teller coupling
      terms are derived for the T2 * (t2 + e) and (E + A) * (e + a) Jahn-Teller
      problems up to arbitrarily high orders. The linear G3/2 * (t2 + e) Jahn-Teller
      Hamiltonian of Moffitt and Thorson [Phys. Rev. 108, 1251 (1957)] for tetrahedral
      systems is generalized to higher orders in vibrational displacements. The Jahn
      Teller Hamiltonians derived in the present work are useful for the interpolation
      and extrapolation of Jahn-Teller distorted potential-energy surfaces of molecules
      and complexes with heavy elements as well as for the calculation of vibronic
      spectra of such systems. 

PMID- 27036422
TI  - Determination of anharmonic free energy contributions: Low temperature phases of
      the Lennard-Jones system.
AB  - We investigate a general method to calculate the free energy of crystalline
      solids by considering the harmonic approximation and quasistatically switching
      the anharmonic contribution. The advantage of this method is that the harmonic
      approximation provides an already very accurate estimate of the free energy, and
      therefore the anharmonic term is numerically very small and can be determined to
      high accuracy. We further show that the anharmonic contribution to the free
      energy satisfies a number of exact inequalities that place constraints on its
      magnitude and allows approximate but fast and accurate estimates. The method is
      implemented into a readily available general software by combining the code
      HOODLT (Highly Optimized Object Oriented Dynamic Lattice Theory) for the harmonic
      part and the molecular dynamics (MD) simulation package HOOMD-blue for the
      anharmonic part. We use the method to calculate the low temperature phase diagram
      for Lennard-Jones particles. We demonstrate that hcp is the equilibrium phase at
      low temperature and pressure and obtain the coexistence curve with the fcc phase,
      which exhibits reentrant behavior. Several implications of the method are
      discussed. 

PMID- 27036423
TI  - A polarizable continuum model for molecules at spherical diffuse interfaces.
AB  - We present an extension of the Polarizable Continuum Model (PCM) to simulate
      solvent effects at diffuse interfaces with spherical symmetry, such as
      nanodroplets and micelles. We derive the form of the Green's function for a
      spatially varying dielectric permittivity with spherical symmetry and exploit the
      integral equation formalism of the PCM for general dielectric environments to
      recast the solvation problem into a continuum solvation framework. This allows
      the investigation of the solvation of ions and molecules in nonuniform dielectric
      environments, such as liquid droplets, micelles or membranes, while maintaining
      the computationally appealing characteristics of continuum solvation models. We
      describe in detail our implementation, both for the calculation of the Green's
      function and for its subsequent use in the PCM electrostatic problem. The model
      is then applied on a few test systems, mainly to analyze the effect of interface
      curvature on solvation energetics. 

PMID- 27036424
TI  - Quadratic integrand double-hybrid made spin-component-scaled.
AB  - We propose two analytical expressions aiming to rationalize the spin-component
      scaled (SCS) and spin-opposite-scaled (SOS) schemes for double-hybrid exchange
      correlation density-functionals. Their performances are extensively tested within
      the framework of the nonempirical quadratic integrand double-hybrid (QIDH) model
      on energetic properties included into the very large GMTKN30 benchmark database,
      and on structural properties of semirigid medium-sized organic compounds. The SOS
      variant is revealed as a less computationally demanding alternative to reach the
      accuracy of the original QIDH model without losing any theoretical background. 

PMID- 27036425
TI  - Distribution of tunnelling times for quantum electron transport.
AB  - In electron transport, the tunnelling time is the time taken for an electron to
      tunnel out of a system after it has tunnelled in. We define the tunnelling time
      distribution for quantum processes in a dissipative environment and develop a
      practical approach for calculating it, where the environment is described by the
      general Markovian master equation. We illustrate the theory by using the rate
      equation to compute the tunnelling time distribution for electron transport
      through a molecular junction. The tunnelling time distribution is exponential,
      which indicates that Markovian quantum tunnelling is a Poissonian statistical
      process. The tunnelling time distribution is used not only to study the quantum
      statistics of tunnelling along the average electric current but also to analyse
      extreme quantum events where an electron jumps against the applied voltage bias.
      The average tunnelling time shows distinctly different temperature dependence for
      p- and n-type molecular junctions and therefore provides a sensitive tool to
      probe the alignment of molecular orbitals relative to the electrode Fermi energy.

PMID- 27036426
TI  - Extending the density functional embedding theory to finite temperature and an
      efficient iterative method for solving for embedding potentials.
AB  - A key element in the density functional embedding theory (DFET) is the embedding
      potential. We discuss two major issues related to the embedding potential: (1)
      its non-uniqueness and (2) the numerical difficulty for solving for it,
      especially for the spin-polarized systems. To resolve the first issue, we extend
      DFET to finite temperature: all quantities, such as the subsystem densities and
      the total system's density, are calculated at a finite temperature. This is a
      physical extension since materials work at finite temperatures. We show that the
      embedding potential is strictly unique at T > 0. To resolve the second issue, we
      introduce an efficient iterative embedding potential solver. We discuss how to
      relax the magnetic moments in subsystems and how to equilibrate the chemical
      potentials across subsystems. The solver is robust and efficient for several non
      trivial examples, in all of which good quality spin-polarized embedding
      potentials were obtained. We also demonstrate the solver on an extended periodic
      system: iron body-centered cubic (110) surface, which is related to the modeling
      of the heterogeneous catalysis involving iron, such as the Fischer-Tropsch and
      the Haber processes. This work would make it efficient and accurate to perform
      embedding simulations of some challenging material problems, such as the
      heterogeneous catalysis and the defects of complicated spin configurations in
      electronic materials. 

PMID- 27036427
TI  - Inelastic effects in molecular transport junctions: The probe technique at high
      bias.
AB  - We extend the Landauer-Buttiker probe formalism for conductances to the high bias
      regime and study the effects of environmentally induced elastic and inelastic
      scattering on charge current in single molecule junctions, focusing on high-bias
      effects. The probe technique phenomenologically incorporates incoherent elastic
      and inelastic effects to the fully coherent case, mimicking a rich physical
      environment at trivial cost. We further identify environmentally induced
      mechanisms which generate an asymmetry in the current, manifested as a weak diode
      behavior. This rectifying behavior, found in two types of molecular junction
      models, is absent in the coherent-elastic limit and is only active in the case
      with incoherent-inelastic scattering. Our work illustrates that in the low bias
      linear response regime, the commonly used "dephasing probe" (mimicking only
      elastic decoherence effects) operates nearly indistinguishably from a "voltage
      probe" (admitting inelastic-dissipative effects). However, these probes realize
      fundamentally distinct I-V characteristics at high biases, reflecting the central
      roles of dissipation and inelastic scattering processes on molecular electronic
      transport far-from-equilibrium. 

PMID- 27036428
TI  - Performance of quantum Monte Carlo for calculating molecular bond lengths.
AB  - This work investigates the accuracy of real-space quantum Monte Carlo (QMC)
      methods for calculating molecular geometries. We present the equilibrium bond
      lengths of a test set of 30 diatomic molecules calculated using variational Monte
      Carlo (VMC) and diffusion Monte Carlo (DMC) methods. The effect of different
      trial wavefunctions is investigated using single determinants constructed from
      Hartree-Fock (HF) and Density Functional Theory (DFT) orbitals with LDA, PBE, and
      B3LYP functionals, as well as small multi-configurational self-consistent field
      (MCSCF) multi-determinant expansions. When compared to experimental geometries,
      all DMC methods exhibit smaller mean-absolute deviations (MADs) than those given
      by HF, DFT, and MCSCF. The most accurate MAD of 3 +/- 2 * 10(-3) A is achieved
      using DMC with a small multi-determinant expansion. However, the more
      computationally efficient multi-determinant VMC method has a similar MAD of only
      4.0 +/- 0.9 * 10(-3) A, suggesting that QMC forces calculated from the relatively
      simple VMC algorithm may often be sufficient for accurate molecular geometries.

PMID- 27036429
TI  - A corpuscular picture of electrons in chemical bond.
AB  - We introduce a theory of chemical bond with a corpuscular picture of electrons.
      It employs a minimal set of localized electron wave packets with "floating and
      breathing" degrees of freedom and the spin-coupling of non-orthogonal valence
      bond theory. Its accuracy for describing potential energy curves of chemical
      bonds in ground and excited states of spin singlet and triplet is examined. 

PMID- 27036430
TI  - Real-space pseudopotential study of vibrational properties and Raman spectra in
      Si-Ge core-shell nanocrystals.
AB  - We examine the vibrational properties and Raman spectra of Si-Ge core-shell
      nanostructures using real-space pseudopotentials constructed within density
      functional theory. Our method uses no empirical parameters, unlike many popular
      methods for predicting Raman spectra for nanocrystals. We find the dominant
      features of the Raman spectrum for the Si-Ge core-shell structure to be a
      superposition of the Raman spectra of the Ge and Si nanocrystals with optical
      peaks around 300 and 500 cm(-1), respectively. We also find a Si-Ge "interface"
      peak at 400 cm(-1). The Ge shell causes the Si core to expand from the
      equilibrium structure. This strain induces significant redshift in the Si
      contribution to the vibrational and Raman spectra, while the Ge shell is largely
      unstrained and does not exhibit this shift. We find that the ratio of peak
      heights is strongly related to the relative size of the core and shell regions.
      This finding suggests that Raman spectroscopy may be used to characterize the
      size of the core and shell in these structures. 

PMID- 27036431
TI  - Exploring the relationship between vibrational mode locality and coupling using
      constrained optimization.
AB  - The use of alternate coordinate systems as a means to improve the efficiency and
      accuracy of anharmonic vibrational structure analysis has seen renewed interest
      in recent years. While normal modes (which diagonalize the mass-weighted Hessian
      matrix) are a typical choice, the delocalized nature of this basis makes it less
      optimal when anharmonicity is in play. When a set of modes is not designed to
      treat anharmonicity, anharmonic effects will contribute to inter-mode coupling in
      an uncontrolled fashion. These effects can be mitigated by introducing locality,
      but this comes at its own cost of potentially large second-order coupling terms.
      Herein, a method is described which partially localizes vibrations to connect the
      fully delocalized and fully localized limits. This allows a balance between the
      treatment of harmonic and anharmonic coupling, which minimizes the error that
      arises from neglected coupling terms. Partially localized modes are investigated
      for a range of model systems including a tetramer of hydrogen fluoride, water
      dimer, ethene, diphenylethane, and stilbene. Generally, partial localization
      reaches ~75% of maximal locality while introducing less than ~30% of the harmonic
      coupling of the fully localized system. Furthermore, partial localization
      produces mode pairs that are spatially separated and thus weakly coupled to one
      another. It is likely that this property can be exploited in the creation of
      model Hamiltonians that omit the coupling parameters of the distant (and
      therefore uncoupled) pairs. 

PMID- 27036432
TI  - Statistical effects related to low numbers of reacting molecules analyzed for a
      reversible association reaction A + B = C in ideally dispersed systems: An
      apparent violation of the law of mass action.
AB  - Theoretical analysis and computer simulations (Monte Carlo and numerical
      integration of differential equations) show that the statistical effect of a
      small number of reacting molecules depends on a way the molecules are distributed
      among the small volume nano-reactors (droplets in this study). A simple
      reversible association A + B = C was chosen as a model reaction, enabling to
      observe both thermodynamic (apparent equilibrium constant) and kinetic effects of
      a small number of reactant molecules. When substrates are distributed uniformly
      among droplets, all containing the same equal number of substrate molecules, the
      apparent equilibrium constant of the association is higher than the chemical one
      (observed in a macroscopic-large volume system). The average rate of the
      association, being initially independent of the numbers of molecules, becomes (at
      higher conversions) higher than that in a macroscopic system: the lower the
      number of substrate molecules in a droplet, the higher is the rate. This results
      in the correspondingly higher apparent equilibrium constant. A quite opposite
      behavior is observed when reactant molecules are distributed randomly among
      droplets: the apparent association rate and equilibrium constants are lower than
      those observed in large volume systems, being the lower, the lower is the average
      number of reacting molecules in a droplet. The random distribution of reactant
      molecules corresponds to ideal (equal sizes of droplets) dispersing of a reaction
      mixture. Our simulations have shown that when the equilibrated large volume
      system is dispersed, the resulting droplet system is already at equilibrium and
      no changes of proportions of droplets differing in reactant compositions can be
      observed upon prolongation of the reaction time. 

PMID- 27036433
TI  - Sampling the isothermal-isobaric ensemble by Langevin dynamics.
AB  - We present a new method of conducting fully flexible-cell molecular dynamics
      simulation in isothermal-isobaric ensemble based on Langevin equations of motion.
      The stochastic coupling to all particle and cell degrees of freedoms is
      introduced in a correct way, in the sense that the stationary configurational
      distribution is proved to be consistent with that of the isothermal-isobaric
      ensemble. In order to apply the proposed method in computer simulations, a second
      order symmetric numerical integration scheme is developed by Trotter's splitting
      of the single-step propagator. Moreover, a practical guide of choosing working
      parameters is suggested for user specified thermo- and baro-coupling time scales.
      The method and software implementation are carefully validated by a numerical
      example. 

PMID- 27036434
TI  - Bimolecular recombination reactions: K-adiabatic and K-active forms of the
      bimolecular master equations and analytic solutions.
AB  - Expressions for a K-adiabatic master equation for a bimolecular recombination
      rate constant krec are derived for a bimolecular reaction forming a complex with
      a single well or complexes with multiple well, where K is the component of the
      total angular momentum along the axis of least moment of inertia of the
      recombination product. The K-active master equation is also considered. The exact
      analytic solutions, i.e., the K-adiabatic and K-active steady-state population
      distribution function of reactive complexes, g(EJK) and g(EJ), respectively, are
      derived for the K-adiabatic and K-active master equation cases using properties
      of inhomogeneous integral equations (Fredholm type). The solutions accommodate
      arbitrary intermolecular energy transfer models, e.g., the single exponential,
      double exponential, Gaussian, step-ladder, and near-singularity models. At the
      high pressure limit, the krec for both the K-adiabatic and K-active master
      equations reduce, respectively, to the K-adiabatic and K-active bimolecular Rice
      Ramsperger-Kassel-Marcus theory (high pressure limit expressions). Ozone and its
      formation from O + O2 are known to exhibit an adiabatic K. The ratio of the K
      adiabatic to the K-active recombination rate constants for ozone formation at the
      high pressure limit is calculated to be ~0.9 at 300 K. Results on the temperature
      and pressure dependence of the recombination rate constants and populations of O3
      will be presented elsewhere. 

PMID- 27036435
TI  - Two-dimensional infrared spectroscopy of vibrational polaritons of molecules in
      an optical cavity.
AB  - Strong coupling of molecular vibrations to an infrared cavity mode affects their
      nature by creating dressed polariton states. We show how the single and double
      vibrational polariton manifolds may be controlled by varying the cavity coupling
      strength and probed by a time domain two-dimensional infrared (2DIR) technique,
      double quantum coherence. Applications are made to the amide-I (CO) and amide-II
      (CN) bond vibrations of N-methylacetamide. 

PMID- 27036436
TI  - Generalized theoretical method for the interaction between arbitrary nonuniform
      electric field and molecular vibrations: Toward near-field infrared spectroscopy
      and microscopy.
AB  - A theoretical method to compute infrared absorption spectra when a molecule is
      interacting with an arbitrary nonuniform electric field such as near-fields is
      developed and numerically applied to simple model systems. The method is based on
      the multipolar Hamiltonian where the light-matter interaction is described by a
      spatial integral of the inner product of the molecular polarization and applied
      electric field. The computation scheme is developed under the harmonic
      approximation for the molecular vibrations and the framework of modern electronic
      structure calculations such as the density functional theory. Infrared reflection
      absorption and near-field infrared absorption are considered as model systems.
      The obtained IR spectra successfully reflect the spatial structure of the applied
      electric field and corresponding vibrational modes, demonstrating applicability
      of the present method to analyze modern nanovibrational spectroscopy using near
      fields. The present method can use arbitral electric fields and thus can
      integrate two fields such as computational chemistry and electromagnetics. 

PMID- 27036437
TI  - Assessing the distinguishable cluster approximation based on the triple bond
      breaking in the nitrogen molecule.
AB  - Obtaining the correct potential energy curves for the dissociation of multiple
      bonds is a challenging problem for ab initio methods which are affected by the
      choice of a spin-restricted reference function. Coupled cluster (CC) methods such
      as CCSD (coupled cluster singles and doubles model) and CCSD(T) (CCSD +
      perturbative triples) correctly predict the geometry and properties at
      equilibrium but the process of bond dissociation, particularly when more than one
      bond is simultaneously broken, is much more complicated. New modifications of CC
      theory suggest that the deleterious role of the reference function can be
      diminished, provided a particular subset of terms is retained in the CC
      equations. The Distinguishable Cluster (DC) approach of Kats and Manby [J. Chem.
      Phys. 139, 021102 (2013)], seemingly overcomes the deficiencies for some bond
      dissociation problems and might be of use in quasi-degenerate situations in
      general. DC along with other approximate coupled cluster methods such as ACCD
      (approximate coupled cluster doubles), ACP-D45, ACP-D14, 2CC, and pCCSD(alpha,
      beta) (all defined in text) falls under a category of methods that are basically
      obtained by the deletion of some quadratic terms in the double excitation
      amplitude equation for CCD/CCSD (coupled cluster doubles model/coupled cluster
      singles and doubles model). Here these approximate methods, particularly those
      based on the DC approach, are studied in detail for the nitrogen molecule bond
      breaking. The N2 problem is further addressed with conventional single reference
      methods but based on spatial symmetry-broken restricted Hartree-Fock (HF)
      solutions to assess the use of these references for correlated calculations in
      the situation where CC methods using fully symmetry adapted SCF solutions fail.
      The distinguishable cluster method is generalized: 1) to different orbitals for
      different spins (unrestricted HF based DCD and DCSD), 2) by adding triples
      correction perturbatively (DCSD(T)) and iteratively (DCSDT-n), and 3) via an
      excited state approximation through the equation of motion (EOM) approach (EOM
      DCD, EOM-DCSD). The EOM-CC method is used to identify lower-energy CC solutions
      to overcome singularities in the CC potential energy curves. It is also shown
      that UHF based CC and DC methods behave very similarly in bond-breaking of N2,
      and that using spatially broken but spin preserving SCF references makes the CCSD
      solutions better than those for DCSD. 

PMID- 27036438
TI  - Revealing electronic open quantum systems with subsystem TDDFT.
AB  - Open quantum systems (OQSs) are perhaps the most realistic systems one can
      approach through simulations. In recent years, describing OQSs with Density
      Functional Theory (DFT) has been a prominent avenue of research with most
      approaches based on a density matrix partitioning in conjunction with an ad-hoc
      description of system-bath interactions. We propose a different theoretical
      approach to OQSs based on partitioning of the electron density. Employing the
      machinery of subsystem DFT (and its time-dependent extension), we provide a novel
      way of isolating and analyzing the various terms contributing to the coupling
      between the system and the surrounding bath. To illustrate the theory, we provide
      numerical simulations on a toy system (a molecular dimer) and on a condensed
      phase system (solvated excimer). The simulations show that non-Markovian dynamics
      in the electronic system-bath interactions are important in chemical
      applications. For instance, we show that the superexchange mechanism of transport
      in donor-bridge-acceptor systems is a non-Markovian interaction between the donor
      acceptor (OQS) with the bridge (bath) which is fully characterized by real-time
      subsystem time-dependent DFT. 

PMID- 27036439
TI  - Energy landscapes for a machine learning application to series data.
AB  - Methods developed to explore and characterise potential energy landscapes are
      applied to the corresponding landscapes obtained from optimisation of a cost
      function in machine learning. We consider neural network predictions for the
      outcome of local geometry optimisation in a triatomic cluster, where four
      distinct local minima exist. The accuracy of the predictions is compared for fits
      using data from single and multiple points in the series of atomic configurations
      resulting from local geometry optimisation and for alternative neural networks.
      The machine learning solution landscapes are visualised using disconnectivity
      graphs, and signatures in the effective heat capacity are analysed in terms of
      distributions of local minima and their properties. 

PMID- 27036440
TI  - Microwave spectral taxonomy: A semi-automated combination of chirped-pulse and
      cavity Fourier-transform microwave spectroscopy.
AB  - Because of its structural specificity, rotational spectroscopy has great
      potential as an analytical tool for characterizing the chemical composition of
      complex gas mixtures. However, disentangling the individual molecular
      constituents of a rotational spectrum, especially if many of the lines are
      entirely new or unknown, remains challenging. In this paper, we describe an
      empirical approach that combines the complementary strengths of two techniques,
      broadband chirped-pulse Fourier transform microwave spectroscopy and narrowband
      cavity Fourier transform microwave spectroscopy, to characterize and assign
      lines. This procedure, called microwave spectral taxonomy, involves acquiring a
      broadband rotational spectrum of a rich mixture, categorizing individual lines
      based on their relative intensities under series of assays, and finally, linking
      rotational transitions of individual chemical compounds within each category
      using double resonance techniques. The power of this procedure is demonstrated
      for two test cases: a stable molecule with a rich spectrum, 3,4
      difluorobenzaldehyde, and products formed in an electrical discharge through a
      dilute mixture of C2H2 and CS2, in which spectral taxonomy has enabled the
      identification of propynethial, HC(S)CCH. 

PMID- 27036441
TI  - Automated microwave double resonance spectroscopy: A tool to identify and
      characterize chemical compounds.
AB  - Owing to its unparalleled structural specificity, rotational spectroscopy is a
      powerful technique to unambiguously identify and characterize volatile, polar
      molecules. We present here a new experimental approach, automated microwave
      double resonance (AMDOR) spectroscopy, to rapidly determine the rotational
      constants of these compounds without a priori knowledge of elemental composition
      or molecular structure. This task is achieved by rapidly acquiring the classical
      (frequency vs. intensity) broadband spectrum of a molecule using chirped-pulse
      Fourier transform microwave (FTMW) spectroscopy and subsequently analyzing it in
      near real-time using complementary cavity FTMW detection and double resonance.
      AMDOR measurements provide a unique "barcode" for each compound from which
      rotational constants can be extracted. To illustrate the power of this approach,
      AMDOR spectra of three aroma compounds - trans-cinnamaldehyde, alpha-, and beta
      ionone - have been recorded and analyzed. The prospects to extend this approach
      to mixture characterization and purity assessment are described. 

PMID- 27036442
TI  - Structures and chemical bonding of B3O3 (-/0) and B3O3H(-/0): A combined
      photoelectron spectroscopy and first-principles theory study.
AB  - We present a combined photoelectron spectroscopy and first-principles theory
      study on the structural and electronic properties and chemical bonding of B3O3 (
      /0) and B3O3H(-/0) clusters. The concerted experimental and theoretical data show
      that the global-minimum structures of B3O3 and B3O3H neutrals are very different
      from those of their anionic counterparts. The B3O3 (-) anion is characterized to
      possess a V-shaped OB-B-BO chain with overall C2 v symmetry (1A), in which the
      central B atom interacts with two equivalent boronyl (B=O) terminals via B-B
      single bonds as well as with one O atom via a B=O double bond. The B3O3H(-) anion
      has a Cs (2A) structure, containing an asymmetric OB-B-OBO zig-zag chain and a
      terminal H atom interacting with the central B atom. In contrast, the C2 v (1a)
      global minimum of B3O3 neutral contains a rhombic B2O2 ring with one B atom
      bonded to a BO terminal and that of neutral B3O3H (2a) is also of C2 v symmetry,
      which is readily constructed from C2 v (1a) by attaching a H atom to the opposite
      side of the BO group. The H atom in B3O3H(-/0) (2A and 2a) prefers to interact
      terminally with a B atom, rather than with O. Chemical bonding analyses reveal a
      three-center four-electron (3c-4e) pi hyperbond in the B3O3H(-) (2A) cluster and
      a four-center four-electron (4c-4e) pi bond (that is, the so-called o-bond) in
      B3O3 (1a) and B3O3H (2a) neutral clusters. 

PMID- 27036443
TI  - Combined theoretical and experimental study of the valence, Rydberg, and ionic
      states of chlorobenzene.
AB  - New photoelectron (PE) and ultra violet (UV) and vacuum UV (VUV) spectra have
      been obtained for chlorobenzene by synchrotron study with higher sensitivity and
      resolution than previous work and are subjected to detailed analysis. In
      addition, we report on the mass-resolved (2 + 1) resonance enhanced multiphoton
      ionization (REMPI) spectra of a jet-cooled sample. Both the VUV and REMPI spectra
      have enabled identification of a considerable number of Rydberg states for the
      first time. The use of ab initio calculations, which include both multi-reference
      multi-root doubles and singles configuration interaction (MRD-CI) and time
      dependent density functional theoretical (TDDFT) methods, has led to major
      advances in interpretation of the vibrational structure of the ionic and
      electronically excited states. Franck-Condon (FC) analyses of the PE spectra,
      including both hot and cold bands, indicate much more complex envelopes than
      previously thought. The sequence of ionic states can be best interpreted by our
      multi-configuration self-consistent field computations and also by comparison of
      the calculated vibrational structure of the B and C ionic states with experiment;
      these conclusions suggest that the leading sequence is the same as that of
      iodobenzene and bromobenzene, namely: X(2)B1(3b1 (-1)) < A(2)A2(1a2 (-1)) <
      B(2)B2(6b2 (-1)) < C(2)B1(2b1 (-1)). The absorption onset near 4.6 eV has been
      investigated using MRD-CI and TDDFT calculations; the principal component of this
      band is (1)B2 and an interpretation based on the superposition of FC and Herzberg
      Teller contributions has been performed. The other low-lying absorption band near
      5.8 eV is dominated by a (1)A1 state, but an underlying weak (1)B1 state
      (pisigma(*)) is also found. The strongest band in the VUV spectrum near 6.7 eV is
      poorly resolved and is analyzed in terms of two pipi(*) states of (1)A1 (higher
      oscillator strength) and (1)B2 (lower oscillator strength) symmetries,
      respectively. The calculated vertical excitation energies of these two states are
      critically dependent upon the presence of Rydberg functions in the basis set,
      since both manifolds are strongly perturbed by the Rydberg states in this energy
      range. A number of equilibrium structures of the ionic and singlet excited states
      show that the molecular structure is less subject to variation than corresponding
      studies for iodobenzene and bromobenzene. 

PMID- 27036444
TI  - Photoelectron velocity-map imaging and theoretical studies of heteronuclear metal
      carbonyls MNi(CO)3(-) (M = Mg, Ca, Al).
AB  - The heteronuclear metal carbonyl anions MNi(CO)3(-) (M = Mg, Ca, Al) have been
      investigated using photoelectron velocity-map imaging spectroscopy. Electron
      affinities of neutral MNi(CO)3 (M = Mg, Ca, Al) are measured from the
      photoelectron spectra to be 1.064 +/- 0.063, 1.050 +/- 0.064, and 1.541 +/- 0.040
      eV, respectively. The C-O stretching mode in these three clusters is observed and
      the vibrational frequency is determined to be 2049, 2000, and 2041 cm(-1) for
      MgNi(CO)3, CaNi(CO)3, and AlNi(CO)3, respectively. Density functional theory
      calculations are carried out to elucidate the geometric and electronic structures
      and to aid the experimental assignments. It has been found that three terminal
      carbonyls are preferentially bonded to the nickel atom in these heterobinuclear
      nickel carbonyls MNi(CO)3 (-1/0), resulting in the formation of the Ni(CO)3
      motif. Ni remains the 18-electron configuration for MgNi(CO)3 and CaNi(CO)3
      neutrals, but not for AlNi(CO)3. This is different from the homobinuclear nickel
      carbonyl Ni-Ni(CO)3 with the involvement of three bridging ligands. Present
      findings would be helpful for understanding CO adsorption on alloy surfaces.

PMID- 27036445
TI  - Isotopic studies of trans- and cis-HOCO using rotational spectroscopy: Formation,
      chemical bonding, and molecular structures.
AB  - HOCO is an important intermediate in combustion and atmospheric processes because
      the OH + CO -> H + CO2 reaction represents the final step for the production of
      CO2 in hydrocarbon oxidation, and theoretical studies predict that this reaction
      proceeds via various intermediates, the most important being this radical.
      Isotopic investigations of trans- and cis-HOCO have been undertaken using Fourier
      transform microwave spectroscopy and millimeter-wave double resonance techniques
      in combination with a supersonic molecular beam discharge source to better
      understand the formation, chemical bonding, and molecular structures of this
      radical pair. We find that trans-HOCO can be produced almost equally well from
      either OH + CO or H + CO2 in our discharge source, but cis-HOCO appears to be
      roughly two times more abundant when starting from H + CO2. Using isotopically
      labelled precursors, the OH + C(18)O reaction predominately yields HOC(18)O for
      both isomers, but H(18)OCO is observed as well, typically at the level of 10%-20%
      that of HOC(18)O; the opposite propensity is found for the (18)OH + CO reaction.
      DO + C(18)O yields similar ratios between DOC(18)O and D(18)OCO as those found
      for OH + C(18)O, suggesting that some fraction of HOCO (or DOCO) may be formed
      from the back-reaction H + CO2, which, at the high pressure of our gas expansion,
      can readily occur. The large (13)C Fermi-contact term (aF) for trans- and cis
      HO(13)CO implicates significant unpaired electronic density in a sigma-type
      orbital at the carbon atom, in good agreement with theoretical predictions. By
      correcting the experimental rotational constants for zero-point vibration motion
      calculated theoretically using second-order vibrational perturbation theory,
      precise geometrical structures have been derived for both isomers. 

PMID- 27036446
TI  - The role of spin-orbit coupling in the photolysis of methylcobalamin.
AB  - The photolysis of the methylcobalamin cofactor (MeCbl) in its base-off form was
      investigated by considering the extent of spin-orbit coupling (SOC). Triplet Co-C
      photodissociation pathways previously invoked at the density functional theory
      level using Landau-Zener theory were further validated with ab initio
      calculations that combine SOC based on multi-state second order perturbation
      theory. It was determined that SOC is feasible between singlet and triplet states
      at elongated Co-C distances, leading to photodissociation from the state having
      dominant sigma(dz(2)) character, by either direct coupling with the lowest
      singlet states or by crossing with SOC mixed triplets.

PMID- 27036447
TI  - Conformational changes in matrix-isolated 6-methoxyindole: Effects of the thermal
      and infrared light excitations.
AB  - Conformational changes induced thermally or upon infrared excitation of matrix
      isolated 6-methoxyindole were investigated. Narrowband near-infrared excitation
      of the first overtone of the N-H stretching vibration of each one of the two
      identified conformers is found to induce a selective large-scale conversion of
      the pumped conformer into the other one. This easily controllable bidirectional
      process consists in the intramolecular reorientation of the methoxy group and
      allowed a full assignment of the infrared spectra of the two conformers. Matrices
      with different conformational compositions prepared by narrow-band irradiations
      were subsequently used to investigate the effects of both thermal and broadband
      infrared excitations on the conformational mixtures. Particular attention is
      given to the influence of the matrix medium (Ar vs. Xe) and conformational
      effects of exposition of the sample to the spectrometer light source during the
      measurements. 

PMID- 27036448
TI  - Search for parity and time reversal violating effects in HgH: Relativistic
      coupled-cluster study.
AB  - The high effective electric field (Eeff) experienced by the unpaired electron in
      an atom or a molecule is one of the key ingredients in the success of electron
      electric dipole moment (eEDM) experiment and its precise calculation requires a
      very accurate theory. We, therefore, employed the Z-vector method in the
      relativistic coupled-cluster framework and found that HgH has a very large Eeff
      value (123.2 GV/cm) which makes it a potential candidate for the next generation
      eEDM experiment. Our study also reveals that it has a large scalar-pseudoscalar
      (S-PS) P,T-violating interaction constant, Ws = 284.2 kHz. To judge the accuracy
      of the obtained results, we have calculated parallel and perpendicular magnetic
      hyperfine structure (HFS) constants and compared with the available experimental
      values. The results of our calculation are found to be in nice agreement with the
      experimental values. Therefore, by looking at the HFS results, we can say that
      both Eeff and Ws values are also very accurate. Further, We have derived the
      relationship between these quantities and the ratio which will help to get model
      independent value of eEDM and S-PS interaction constant. 

PMID- 27036449
TI  - Gas phase vibrational spectroscopy of cold (TiO2)n(-) (n = 3-8) clusters.
AB  - We report infrared photodissociation (IRPD) spectra for the D2-tagged titanium
      oxide cluster anions (TiO2)n(-) with n = 3-8 in the spectral region from 450 to
      1200 cm(-1). The IRPD spectra are interpreted with the aid of harmonic spectra
      from BP86/6-311+G* density functional theory calculations of energetically low
      lying isomers. We conclusively assign the IRPD spectra of the n = 3 and n = 6
      clusters to global minimum energy structures with Cs and C2 symmetry,
      respectively. The vibrational spectra of the n = 4 and n = 7 clusters can be
      attributed to contributions of at most two low-lying structures. While our
      calculations indicate that the n = 5 and n = 8 clusters have many more low-lying
      isomers than the other clusters, the dominant contributions to their spectra can
      be assigned to the lowest energy structures. Through comparison between the
      calculated and experimental spectra, we can draw conclusions about the size
      dependent evolution of the properties of (TiO2)n(-) clusters, and on their
      potential utility as model systems for catalysis on a bulk TiO2 surface.

PMID- 27036450
TI  - Theoretical and experimental differential cross sections for electron impact
      excitation of the electronic bands of furfural.
AB  - We report results from a joint experimental and theoretical investigation into
      electron scattering from the important industrial species furfural (C5H4O2).
      Specifically, differential cross sections (DCSs) have been measured and
      calculated for the electron-impact excitation of the electronic states of C5H4O2.
      The measurements were carried out at energies in the range 20-40 eV, and for
      scattered-electron angles between 10 degrees  and 90 degrees . The energy
      resolution of those experiments was typically ~80 meV. Corresponding Schwinger
      multichannel method with pseudo-potential calculations, for energies between 6-50
      eV and with and without Born-closure, were also performed for a sub-set of the
      excited electronic-states that were accessed in the measurements. Those
      calculations were undertaken at the static exchange plus polarisation-level using
      a minimum orbital basis for single configuration interaction (MOB-SCI) approach.
      Agreement between the measured and calculated DCSs was qualitatively quite good,
      although to obtain quantitative accord, the theory would need to incorporate even
      more channels into the MOB-SCI. The role of multichannel coupling on the computed
      electronic-state DCSs is also explored in some detail. 

PMID- 27036451
TI  - The electron-furfural scattering dynamics for 63 energetically open electronic
      states.
AB  - We report on integral-, momentum transfer- and differential cross sections for
      elastic and electronically inelastic electron collisions with furfural (C5H4O2).
      The calculations were performed with two different theoretical methodologies, the
      Schwinger multichannel method with pseudopotentials (SMCPP) and the independent
      atom method with screening corrected additivity rule (IAM-SCAR) that now
      incorporates a further interference (I) term. The SMCPP with N energetically open
      electronic states (N(open)) at either the static-exchange (N(open) ch-SE) or the
      static-exchange-plus-polarisation (N(open) ch-SEP) approximation was employed to
      calculate the scattering amplitudes at impact energies lying between 5 eV and 50
      eV, using a channel coupling scheme that ranges from the 1ch-SEP up to the 63ch
      SE level of approximation depending on the energy considered. For elastic
      scattering, we found very good overall agreement at higher energies among our
      SMCPP cross sections, our IAM-SCAR+I cross sections and the experimental data for
      furan (a molecule that differs from furfural only by the substitution of a
      hydrogen atom in furan with an aldehyde functional group). This is a good
      indication that our elastic cross sections are converged with respect to the
      multichannel coupling effect for most of the investigated intermediate energies.
      However, although the present application represents the most sophisticated
      calculation performed with the SMCPP method thus far, the inelastic cross
      sections, even for the low lying energy states, are still not completely
      converged for intermediate and higher energies. We discuss possible reasons
      leading to this discrepancy and point out what further steps need to be
      undertaken in order to improve the agreement between the calculated and measured
      cross sections.

PMID- 27036452
TI  - Transition state region in the A-Band photodissociation of allyl iodide--A
      femtosecond extreme ultraviolet transient absorption study.
AB  - Femtosecond extreme ultraviolet (XUV) transient absorption spectroscopy based on
      a high-harmonic generation source is used to study the 266 nm induced A-band
      photodissociation dynamics of allyl iodide (CH2 =CHCH2I). The photolysis of the C
      I bond at this wavelength produces iodine atoms both in the ground ((2)P3/2, I)
      and spin-orbit excited ((2)P1/2, I*) states, with the latter as the predominant
      channel. Using XUV absorption at the iodine N4/5 edge (45-60 eV), the experiments
      constitute a direct probe of not only the long-lived atomic iodine reaction
      products but also the fleeting transition state region of the repulsive
      nIsigma(*) C-I excited states. Specifically, three distinct features are
      identified in the XUV transient absorption spectrum at 45.3 eV, 47.4 eV, and 48.4
      eV (denoted transients A, B, and C, respectively), which arise from the repulsive
      valence-excited nsigma(*) states and project onto the high-lying core-excited
      states of the dissociating molecule via excitation of 4d(I) core electrons.
      Transients A and B originate from 4d(I) -> n(I) core-to-valence transitions,
      whereas transient C is best assigned to a 4d(I) ->sigma(*)(C-I) transition. The
      measured differential absorbance of these new features along with the I/I*
      branching ratios known from the literature is used to suggest a more definitive
      assignment, albeit provisional, of the transients to specific dissociative states
      within the A-band manifold. The transients are found to peak around 55 fs-65 fs
      and decay completely by 145 fs-185 fs, demonstrating the ability of XUV
      spectroscopy to map the evolution of reactants into products in real time. The
      similarity in the energies of transients A and B with analogous features observed
      in methyl iodide [Attar et al. J. Phys. Chem. Lett. 6, 5072, (2015)] together
      with the new observation of transient C in the present work provides a more
      complete picture of the valence electronic structure in the transition state
      region. The results provide a benchmark for theoretical calculations on the
      nature of core-excited states in halogenated hydrocarbons, especially in the
      transition state region along the C-I reaction coordinate. 

PMID- 27036453
TI  - An improved quasi-diabatic representation of the 1, 2, 3(1)A coupled adiabatic
      potential energy surfaces of phenol in the full 33 internal coordinates.
AB  - In a recent work we constructed a quasi-diabatic representation, H(d), of the 1,
      2, 3(1)A adiabatic states of phenol from high level multireference single and
      double excitation configuration interaction electronic structure data, energies,
      energy gradients, and derivative couplings. That H(d) accurately describes
      surface minima, saddle points, and also regions of strong nonadiabatic
      interactions, reproducing the locus of conical intersection seams and the
      coordinate dependence of the derivative couplings. The present work determines
      the accuracy of H(d) for describing phenol photodissociation. Additionally, we
      demonstrate that a modest energetic shift of two diabats yields a quantifiably
      more accurate H(d) compared with experimental energetics. The analysis shows that
      in favorable circumstances it is possible to use single point energies obtained
      from the most reliable electronic structure methods available, including methods
      for which the energy gradients and derivative couplings are not available, to
      improve the quality of a global representation of several coupled potential
      energy surfaces. Our data suggest an alternative interpretation of kinetic energy
      release measurements near lambdaphot ~ 248 nm. 

PMID- 27036454
TI  - Modification of chirped laser pulses via delayed rotational nonlinearity.
AB  - To interpret single-shot measurements of rotational revival patterns in molecular
      gases excited by an ultrashort laser pulse, an analytical description of the
      probe pulse modulation by the impulsively excited medium is developed. A
      femtosecond pump laser pulse prepares a rotational wavepacket in a gas-phase
      sample, and the resulting periodic revivals are mapped into the frequency domain
      by using a substantially chirped continuum probe pulse. Since the standard
      approximate descriptions of probe pulse propagation are inapplicable (such as the
      slowly varying envelope approximation and the slowly evolving wave
      approximation), we propose an approach capable of incorporating both the
      substantial chirp of the pulse and the temporal dispersion of the medium
      response. Theory is presented for the case where the frequency change of the
      probe during the probe pulse duration is comparable with the carrier frequency.
      Analytical expressions are obtained for the probe signal modulation over the pump
      probe interaction region and for the resulting heterodyned transient
      birefringence spectra. The approach is illustrated using the case of nitrogen
      gas. 

PMID- 27036455
TI  - Mutual diffusion of binary liquid mixtures containing methanol, ethanol, acetone,
      benzene, cyclohexane, toluene, and carbon tetrachloride.
AB  - Mutual diffusion coefficients of all 20 binary liquid mixtures that can be formed
      out of methanol, ethanol, acetone, benzene, cyclohexane, toluene, and carbon
      tetrachloride without a miscibility gap are studied at ambient conditions of
      temperature and pressure in the entire composition range. The considered mixtures
      show a varying mixing behavior from almost ideal to strongly non-ideal.
      Predictive molecular dynamics simulations employing the Green-Kubo formalism are
      carried out. Radial distribution functions are analyzed to gain an understanding
      of the liquid structure influencing the diffusion processes. It is shown that
      cluster formation in mixtures containing one alcoholic component has a
      significant impact on the diffusion process. The estimation of the thermodynamic
      factor from experimental vapor-liquid equilibrium data is investigated,
      considering three excess Gibbs energy models, i.e., Wilson, NRTL, and UNIQUAC. It
      is found that the Wilson model yields the thermodynamic factor that best suits
      the simulation results for the prediction of the Fick diffusion coefficient. Four
      semi-empirical methods for the prediction of the self-diffusion coefficients and
      nine predictive equations for the Fick diffusion coefficient are assessed and it
      is found that methods based on local composition models are more reliable.
      Finally, the shear viscosity and thermal conductivity are predicted and in most
      cases favorably compared with experimental literature values. 

PMID- 27036456
TI  - Evaporative cooling of microscopic water droplets in vacuo: Molecular dynamics
      simulations and kinetic gas theory.
AB  - In the present study, we investigate the process of evaporative cooling of
      nanometer-sized droplets in vacuum using molecular dynamics simulations with the
      TIP4P/2005 water model. The results are compared to the temperature evolution
      calculated from the Knudsen theory of evaporation which is derived from kinetic
      gas theory. The calculated and simulation results are found to be in very good
      agreement for an evaporation coefficient equal to unity. Our results are of
      interest to experiments utilizing droplet dispensers as well as to cloud micro
      physics. 

PMID- 27036457
TI  - First-principles study on equation of states and electronic structures of shock
      compressed Ar up to warm dense regime.
AB  - The equation of states (EOS) and electronic structures of argon with temperatures
      from 0.02 eV to 3 eV and densities from 0.5 g/cm(3) to 5.5 g/cm(3) are calculated
      using the pair potential and many-body potential molecular dynamics and the
      density functional theory (DFT) molecular dynamics with van der Waals (vdW)
      corrections. First-principles molecular dynamics is implemented above 2.0
      g/cm(3). For the cases of low densities below 3 g/cm(3), we performed pair
      potential molecular dynamics in order to obtain the ionic configurations, which
      are used in density functional theory to calculate the EOS and electronic
      structures. We checked the validity of different methods at different densities
      and temperatures, showing their behaviors by comparing EOS. DFT without vdW
      correction works well above 1 eV and 3.5 g/cm(3). Below 1 eV and 2.0 g/cm(3), it
      overestimates the pressure apparently and results in incorrect behaviors of the
      internal energy. With vdW corrections, the semi-empirical force-field correction
      (DFT-D2) method gives consistent results in the whole density and temperature
      region, and the vdW density functional (vdW-DF2) method gives good results below
      2.5 g/cm(3), but it overestimates the pressure at higher densities. The
      interactions among the atoms are overestimated by the pair potential above 1 eV,
      and a temperature dependent scaled pair potential can be used to correct the
      ionic configurations of the pair potential up to 3 eV. The comparisons between
      our calculations and the experimental multi-shock compression results show that
      the Hugoniot line of DFT-D2 and DFT tends to give larger pressure than the
      results of the self-consistent fluid variational theory, and the difference
      increases with the density. The electronic energy gap exists for all our cases up
      to 5.5 g/cm(3) and 1 eV. The effect of vdW interactions on the electronic
      structures are also discussed. 

PMID- 27036458
TI  - Consensus on the solubility of NaCl in water from computer simulations using the
      chemical potential route.
AB  - The solubility of NaCl in water is evaluated by using three force field models:
      Joung-Cheatham for NaCl dissolved in two different water models (SPC/E and
      TIP4P/2005) and Smith Dang NaCl model in SPC/E water. The methodology based on
      free-energy calculations [E. Sanz and C. Vega, J. Chem. Phys. 126, 014507 (2007)]
      and [J. L. Aragones et al., J. Chem. Phys. 136, 244508 (2012)] has been used,
      except, that all calculations for the NaCl in solution were obtained by using
      molecular dynamics simulations with the GROMACS package instead of homemade MC
      programs. We have explored new lower molalities and made longer runs to improve
      the accuracy of the calculations. Exploring the low molality region allowed us to
      obtain an analytical expression for the chemical potential of the ions in
      solution as a function of molality valid for a wider range of molalities,
      including the infinite dilute case. These new results are in better agreement
      with recent estimations of the solubility obtained with other methodologies.
      Besides, two empirical simple rules have been obtained to have a rough estimate
      of the solubility of a certain model, by analyzing the ionic pairs formation as a
      function of molality and/or by calculating the difference between the NaCl solid
      chemical potential and the standard chemical potential of the salt in solution. 

PMID- 27036459
TI  - High temperature breakdown of the Stokes-Einstein relation in a computer
      simulated Cu-Zr melt.
AB  - Transport properties and the Stokes-Einstein (SE) relation in liquid Cu8Zr3 are
      studied by molecular dynamics simulation with a modified embedded atom potential.
      The critical temperature Tc of mode coupling theory (MCT) is derived as 930 K
      from the self-diffusion coefficient D and viscosity eta. The SE relation breaks
      down around TSE = 1900 K, which is far above Tc. At temperatures below TSE, the
      product of D and eta fluctuates around a constant value, similar to the
      prediction of MCT near Tc. The influence of the microscopic atomic motion on
      macroscopic properties is investigated by analyzing the time dependent liquid
      structure and the self-hole filling process. The self-holes for the two
      components are preferentially filled by atoms of the same component. The self
      hole filling dynamics explains the different breakdown behaviors of the SE
      relation in Zr-rich liquid CuZr2 compared to Cu-rich Cu8Zr3. At TSE, a kink is
      found in the temperature dependence of both partial and total coordination
      numbers for the three atomic pair combinations and of the typical time of self
      hole filling. This indicates a strong correlation between liquid structure,
      atomic dynamics, and the breakdown of SE relation. The previously suggested
      usefulness of the parameter d(D1/D2)/dT to predict TSE is confirmed. Additionally
      we propose a viscosity criterion to predict TSE in the absence of diffusion data.

PMID- 27036460
TI  - Structural anomaly and dynamic heterogeneity in cycloether/water binary mixtures:
      Signatures from composition dependent dynamic fluorescence measurements and
      computer simulations.
AB  - We have performed steady state UV-visible absorption and time-resolved
      fluorescence measurements and computer simulations to explore the cosolvent mole
      fraction induced changes in structural and dynamical properties of water/dioxane
      (Diox) and water/tetrahydrofuran (THF) binary mixtures. Diox is a quadrupolar
      solvent whereas THF is a dipolar one although both are cyclic molecules and
      represent cycloethers. The focus here is on whether these cycloethers can induce
      stiffening and transition of water H-bond network structure and, if they do,
      whether such structural modification differentiates the chemical nature (dipolar
      or quadrupolar) of the cosolvent molecules. Composition dependent measured
      fluorescence lifetimes and rotation times of a dissolved dipolar solute (Coumarin
      153, C153) suggest cycloether mole-fraction (X(THF)/Diox) induced structural
      transition for both of these aqueous binary mixtures in the 0.1 <= X(THF)/Diox <=
      0.2 regime with no specific dependence on the chemical nature. Interestingly,
      absorption measurements reveal stiffening of water H-bond structure in the
      presence of both the cycloethers at a nearly equal mole-fraction, X(THF)/Diox ~
      0.05. Measurements near the critical solution temperature or concentration
      indicate no role for the solution criticality on the anomalous structural
      changes. Evidences for cycloether aggregation at very dilute concentrations have
      been found. Simulated radial distribution functions reflect abrupt changes in
      respective peak heights at those mixture compositions around which fluorescence
      measurements revealed structural transition. Simulated water coordination numbers
      (for a dissolved C153) and number of H-bonds also exhibit minima around these
      cosolvent concentrations. In addition, several dynamic heterogeneity parameters
      have been simulated for both the mixtures to explore the effects of structural
      transition and chemical nature of cosolvent on heterogeneous dynamics of these
      systems. Simulated four-point dynamic susceptibility suggests formation of
      clusters inducing local heterogeneity in the solution structure.

PMID- 27036461
TI  - High pressure structural changes in aluminium triiodide: A first principles
      study.
AB  - First principles calculations identified a phase transition in aluminium
      triiodide (AlI3) and predicted its physical and spectroscopic properties under
      high pressure conditions. A high pressure monoclinic phase is predicted to exist
      above 1.3 GPa accompanied with a coordination change of aluminium resulting from
      a transformation from the ambient pressure 4-coordinated primitive monoclinic
      phase with space group P21/c to the monoclinic 6-coordinated structure with space
      group C2/m. Density functional phonon calculations predicted its dynamical and
      mechanical stability. Infrared effective charge intensities and Raman scattering
      tensors were obtained to characterize its spectroscopic properties. First
      principles metadynamics simulations were employed to reconstruct this phase
      transition and provide the mechanism details for energetically favourable path
      from the ambient pressure P21/c structure to the predicted C2/m structure. 

PMID- 27036462
TI  - Long range stress correlations in the inherent structures of liquids at rest.
AB  - Simulation studies of the atomic shear stress in the local potential energy
      minima (inherent structures) are reported for binary liquid mixtures in 2D and
      3D. These inherent structure stresses are fundamental to slow stress relaxation
      and high viscosity in supercooled liquids. We find that the atomic shear stress
      in the inherent structures (IS's) of both liquids at rest exhibits slowly
      decaying anisotropic correlations. We show that the stress correlations
      contribute significantly to the variance of the total shear stress of the IS
      configurations and consider the origins of the anisotropy and spatial extent of
      the stress correlations. 

PMID- 27036463
TI  - Residual entropy of ice III from Monte Carlo simulation.
AB  - We calculated the residual entropy of ice III as a function of the occupation
      probabilities of hydrogen positions alpha and beta assuming equal energies of all
      configurations. To do this, a discrete ice model with Bjerrum defect energy
      penalty and harmonic terms to constrain the occupation probabilities was
      simulated by the Metropolis Monte Carlo method for a range of temperatures and
      sizes followed by thermodynamic integration and extrapolation to N = infinity.
      Similarly as for other ices, the residual entropies are slightly higher than the
      mean-field (no-loop) approximation. However, the corrections caused by
      fluctuation of energies of ice samples calculated using molecular models of water
      are too large for accurate determination of the chemical potential and phase
      equilibria. 

PMID- 27036464
TI  - Evaluation of the grand-canonical partition function using expanded Wang-Landau
      simulations. IV. Performance of many-body force fields and tight-binding schemes
      for the fluid phases of silicon.
AB  - We extend Expanded Wang-Landau (EWL) simulations beyond classical systems and
      develop the EWL method for systems modeled with a tight-binding Hamiltonian. We
      then apply the method to determine the partition function and thus all
      thermodynamic properties, including the Gibbs free energy and entropy, of the
      fluid phases of Si. We compare the results from quantum many-body (QMB) tight
      binding models, which explicitly calculate the overlap between the atomic
      orbitals of neighboring atoms, to those obtained with classical many-body (CMB)
      force fields, which allow to recover the tetrahedral organization in condensed
      phases of Si through, e.g., a repulsive 3-body term that favors the ideal
      tetrahedral angle. Along the vapor-liquid coexistence, between 3000 K and 6000 K,
      the densities for the two coexisting phases are found to vary significantly (by 5
      orders of magnitude for the vapor and by up to 25% for the liquid) and to provide
      a stringent test of the models. Transitions from vapor to liquid are predicted to
      occur for chemical potentials that are 10%-15% higher for CMB models than for QMB
      models, and a ranking of the force fields is provided by comparing the
      predictions for the vapor pressure to the experimental data. QMB models also
      reveal the formation of a gap in the electronic density of states of the
      coexisting liquid at high temperatures. Subjecting Si to a nanoscopic confinement
      has a dramatic effect on the phase diagram with, e.g. at 6000 K, a decrease in
      liquid densities by about 50% for both CMB and QMB models and an increase in
      vapor densities between 90% (CMB) and 170% (QMB). The results presented here
      provide a full picture of the impact of the strategy (CMB or QMB) chosen to model
      many-body effects on the thermodynamic properties of the fluid phases of Si. 

PMID- 27036465
TI  - Linking density functional and mode coupling models for supercooled liquids.
AB  - We compare predictions from two familiar models of the metastable supercooled
      liquid, respectively, constructed with thermodynamic and dynamic approaches. In
      the so called density functional theory the free energy F[rho] of the liquid is a
      functional of the inhomogeneous density rho(r). The metastable state is
      identified as a local minimum of F[rho]. The sharp density profile characterizing
      rho(r) is identified as a single particle oscillator, whose frequency is obtained
      from the parameters of the optimum density function. On the other hand, a dynamic
      approach to supercooled liquids is taken in the mode coupling theory (MCT) which
      predict a sharp ergodicity-non-ergodicity transition at a critical density. The
      single particle dynamics in the non-ergodic state, treated approximately,
      represents a propagating mode whose characteristic frequency is computed from the
      corresponding memory function of the MCT. The mass localization parameters in the
      above two models (treated in their simplest forms) are obtained, respectively, in
      terms of the corresponding natural frequencies depicted and are shown to have
      comparable magnitudes. 

PMID- 27036466
TI  - Lattice constants of pure methane and carbon dioxide hydrates at low
      temperatures. Implementing quantum corrections to classical molecular dynamics
      studies.
AB  - We introduce a simple correction to the calculation of the lattice constants of
      fully occupied structure sI methane or carbon dioxide pure hydrates that are
      obtained from classical molecular dynamics simulations using the TIP4PQ/2005
      water force field. The obtained corrected lattice constants are subsequently used
      in order to obtain isobaric thermal expansion coefficients of the pure gas
      hydrates that exhibit a trend that is significantly closer to the experimental
      behavior than previously reported classical molecular dynamics studies. 

PMID- 27036467
TI  - Structural, dynamical, and transport properties of the hydrated halides: How do
      At(-) bulk properties compare with those of the other halides, from F(-) to I(-)?
AB  - The properties of halides from the lightest, fluoride (F(-)), to the heaviest,
      astatide (At(-)), have been studied in water using a polarizable force-field
      approach based on molecular dynamics (MD) simulations at the 10 ns scale. The
      selected force-field explicitly treats the cooperativity within the halide-water
      hydrogen bond networks. The force-field parameters have been adjusted to ab
      initio data on anion/water clusters computed at the relativistic Moller-Plesset
      second-order perturbation theory level of theory. The anion static
      polarizabilities of the two heaviest halides, I(-) and At(-), were computed in
      the gas phase using large and diffuse atomic basis sets, and taking into account
      both electron correlation and spin-orbit coupling within a four-component
      framework. Our MD simulation results show the solvation properties of I(-) and
      At(-) in aqueous phase to be very close. For instance, their first hydration
      shells are structured and encompass 9.2 and 9.1 water molecules at about 3.70 +/-
      0.05 A, respectively. These values have to be compared to the F(-), Cl(-), and
      Br(-) ones, i.e., 6.3, 8.4, and 9.0 water molecules at 2.74, 3.38, and 3.55 A,
      respectively. Moreover our computations predict the solvation free energy of At(
      ) in liquid water at ambient conditions to be 68 kcal mol(-1), a value also close
      the I(-) one, about 70 kcal mol(-1). In all, our simulation results for I(-) are
      in excellent agreement with the latest neutron- and X-ray diffraction studies.
      Those for the At(-) ion are predictive, as no theoretical or experimental data
      are available to date. 

PMID- 27036468
TI  - Mode-coupling theoretical study on the roles of heterogeneous structure in
      rheology of ionic liquids.
AB  - Theoretical calculations of the rheological properties of coarse-grained model
      ionic liquids were performed using mode-coupling theory. The nonpolar part of the
      cation was systematically increased in order to clarify the effects of the
      heterogeneous structure on shear viscosity. The shear viscosity showed a minimum
      as the function of the size of the nonpolar part, as had been reported in
      literatures. The minimum was ascribed to the interplay between the increase in
      the shear relaxation time and the decrease in the high-frequency shear modulus
      with increasing the size of the nonpolar part of the cation. The ionic liquids
      with symmetric charge distribution of cations were less viscous than those with
      asymmetric cations, which is also in harmony with experiments. The theoretical
      analysis demonstrated that there are two mechanisms for the higher viscosity of
      the asymmetric model. The first one is the direct coupling between the domain
      dynamics and the shear stress. The second one is that the microscopic dynamics
      within the polar domain is retarded due to the nonlinear coupling with the
      heterogeneous structure. 

PMID- 27036469
TI  - STM study of PTCDA on Sn/Si(111)-2?3*2?3.
AB  - The electronic structures of perylene tetracarboxylic dianhydride on Sn/Si(111)
      2?3*2?3 have been studied by scanning tunneling microscopy and spectroscopy.
      Individual molecules have been investigated at 0.15 ML, while at 0.3 ML molecules
      formed short rods. At 0.6 ML, the molecular rods interacted with each other,
      coupling with the substrate and forming a new 4?3*2?3 super structure. At 0.9 ML,
      the surface was further reconstructed and consisted of strips with two and three
      rods of molecules. We found that these surface structures are strongly modified
      by the molecule/substrate and the intermolecular interactions. As a result, the
      HOMO-LUMO gaps of these molecules change with respect to the phases and the
      thickness. For a single molecular layer of the 4?3*2?3 phase, the HOMO-LUMO
      levels were split with a gap of approximately 2.1 eV, which is caused by charge
      transfer from the substrate to the molecules.

PMID- 27036470
TI  - Key parameters controlling the performance of catalytic motors.
AB  - The development of autonomous micro/nanomotors driven by self-generated chemical
      gradients is a topic of high interest given their potential impact in medicine
      and environmental remediation. Although impressive functionalities of these
      devices have been demonstrated, a detailed understanding of the propulsion
      mechanism is still lacking. In this work, we perform a comprehensive numerical
      analysis of the key parameters governing the actuation of bimetallic catalytic
      micropumps. We show that the fluid motion is driven by self-generated electro
      osmosis where the electric field originates by a proton current rather than by a
      lateral charge asymmetry inside the double layer. Hence, the surface potential
      and the electric field are the key parameters for setting the pumping strength
      and directionality. The proton flux that generates the electric field stems from
      the proton gradient induced by the electrochemical reactions taken place at the
      pump. Surprisingly the electric field and consequently the fluid flow are mainly
      controlled by the ionic strength and not by the conductivity of the solution, as
      one could have expected. We have also analyzed the influence of the chemical fuel
      concentration, electrochemical reaction rates, and size of the metallic
      structures for an optimized pump performance. Our findings cast light on the
      complex chemomechanical actuation of catalytic motors and provide important clues
      for the search, design, and optimization of novel catalytic actuators. 

PMID- 27036471
TI  - Flow-induced voltage generation by moving a nano-sized ionic liquids droplet over
      a graphene sheet: Molecular dynamics simulation.
AB  - In this work, the phenomenon of the voltage generation is explored by using the
      molecular dynamics simulations, which is performed by driving a nano-sized
      droplet of room temperature ionic liquids moving along the monolayer graphene
      sheet for the first time. The studies show that the cations and anions of the
      droplet will move with velocity nonlinearly increasing to saturation arising by
      the force balance. The traditional equation for calculating the induced voltage
      is developed by taking the charge density into consideration, and larger induced
      voltages in MUV-scale are obtained from the nano-size simulation systems based on
      the ionic liquids (ILs) for its enhanced ionic drifting velocities. It is also
      derived that the viscosity acts as a reduction for the induced voltage by
      comparing systems composed of two types of ILs with different viscosity and
      temperature. 

PMID- 27036472
TI  - Excited-state dynamics of size-dependent colloidal TiO2-Au nanocomposites.
AB  - The ultrafast excited-state dynamics of size-dependent TiO2-Au nanocomposites
      synthesized by reducing gold nanoclusters to the surface of colloidal TiO2
      nanoparticles are studied using pump-probe transient absorption spectroscopy with
      400 nm excitation pulses. The results show that the relaxation processes of the
      plasmon depletion band, which are described by electron-phonon and phonon-phonon
      scattering lifetimes, are independent of the gold nanocluster shell size
      surrounding the TiO2 nanoparticle core. The dynamics corresponding to interfacial
      electron transfer between the gold nanoclusters and the TiO2 bandgap are observed
      to spectrally overlap with the gold interband transition signal, and the electron
      transfer lifetimes are shown to significantly decrease as the nanocluster shell
      size increases. Additionally, size-dependent periodic oscillations are observed
      and are attributed to acoustic phonons of a porous shell composed of aggregated
      gold nanoclusters around the TiO2 core, with frequencies that decrease and
      damping times that remain constant as the nanocluster shell size increases. These
      results are important for the development of improved catalytic nanomaterial
      applications. 

PMID- 27036473
TI  - Isotropic and nematic liquid crystalline phases of adaptive rotaxanes.
AB  - We describe the thermodynamics of a solution of rotaxanes which can change their
      length from a short state of length L to a long state of length qL in response to
      their surrounding environment. We call these rotaxanes "adaptive." We show that
      such a system can exhibit both isotropic and nematic liquid crystalline phases.
      The system shows several interesting kinds of behaviour. First we predict that
      the fraction of short-length rotaxanes increases linearly with concentration and
      is a maximum at the critical concentration that marks the isotropic to nematic
      transition. Second, the critical concentration shows a minimum at a certain value
      of q. Our model suggests that the effect of adaptive length changes is most
      dramatic at small q and where the long state is slightly favoured. 

PMID- 27036474
TI  - A non-additive repulsive contribution in an equation of state: The development
      for homonuclear square well chains equation of state validated against Monte
      Carlo simulation.
AB  - This work consists of the adaptation of a non-additive hard sphere theory
      inspired by Malakhov and Volkov [Polym. Sci., Ser. A 49(6), 745-756 (2007)] to a
      square-well chain. Using the thermodynamic perturbation theory, an additional
      term is proposed that describes the effect of perturbing the chain of square well
      spheres by a non-additive parameter. In order to validate this development, NPT
      Monte Carlo simulations of thermodynamic and structural properties of the non
      additive square well for a pure chain and a binary mixture of chains are
      performed. Good agreements are observed between the compressibility factors
      originating from the theory and those from molecular simulations. 

PMID- 27036475
TI  - Soft matter dynamics: Accelerated fluid squeeze-out during slip.
AB  - Using a Leonardo da Vinci experimental setup (constant driving force), we study
      the dependency of lubricated rubber friction on the time of stationary contact
      and on the sliding distance. We slide rectangular rubber blocks on smooth polymer
      surfaces lubricated by glycerol or by a grease. We observe a remarkable effect:
      during stationary contact the lubricant is only very slowly removed from the
      rubber-polymer interface, while during slip it is very rapidly removed resulting
      (for the grease lubricated surface) in complete stop of motion after a short time
      period, corresponding to a slip distance typically of order only a few times the
      length of the rubber block in the sliding direction. For an elastically stiff
      material, poly(methyl methacrylate), we observe the opposite effect: the sliding
      speed increases with time (acceleration), and the lubricant film thickness
      appears to increase. We propose an explanation for the observed effect based on
      transient elastohydrodynamics, which may be relevant also for other soft
      contacts. 

PMID- 27036476
TI  - Fluids density functional theory and initializing molecular dynamics simulations
      of block copolymers.
AB  - Classical, fluids density functional theory (fDFT), which can predict the
      equilibrium density profiles of polymeric systems, and coarse-grained molecular
      dynamics (MD) simulations, which are often used to show both structure and
      dynamics of soft materials, can be implemented using very similar bead-based
      polymer models. We aim to use fDFT and MD in tandem to examine the same system
      from these two points of view and take advantage of the different features of
      each methodology. Additionally, the density profiles resulting from fDFT
      calculations can be used to initialize the MD simulations in a close to
      equilibrated structure, speeding up the simulations. Here, we show how this
      method can be applied to study microphase separated states of both typical
      diblock and tapered diblock copolymers in which there is a region with a gradient
      in composition placed between the pure blocks. Both methods, applied at constant
      pressure, predict a decrease in total density as segregation strength or the
      length of the tapered region is increased. The predictions for the density
      profiles from fDFT and MD are similar across materials with a wide range of
      interfacial widths. 

PMID- 27036477
TI  - Solution of the complete Curtiss-Bird model for polymeric liquids subjected to
      simple shear flow.
AB  - The complete kinetic theory model for concentrated polymer solutions and melts
      proposed by Curtiss and Bird is solved for shear flow: (a) analytically by
      providing a solution for the single-link (or configurational) distribution
      function as a real basis spherical harmonics expansion and then calculating the
      materials functions in shear flow up to second order in the dimensionless shear
      rate and, (b) numerically via the execution of Brownian dynamics simulations.
      These two methods are actually complementary to each other as the former is
      accurate only for small dimensionless shear rates where the latter produces
      results with increasingly large uncertainties. The analytical expansions of the
      material functions with respect to the dimensionless shear rate reduce to those
      of the extensively studied, simplified Curtiss-Bird model when epsilon' = 0, and
      to the rigid rod when epsilon' = 1. It is known that the power-law behavior at
      high shear rates is very different for these two extremal cases. We employ
      Brownian dynamics simulation to not only recover the limiting cases but to find a
      gradual variation of the power-law behaviors at large dimensionless shear rates
      upon varying epsilon'. The fact that experimental data are usually located
      between these two extremes strongly advocates the significance of studying the
      solution of the Curtiss-Bird model. This is exemplified in this work by comparing
      the solution of this model with available rheological data for semiflexible
      biological systems that are clearly not captured by the original Doi-Edwards or
      simplified Curtiss-Bird models. 

PMID- 27036478
TI  - Lattice model of oligonucleotide hybridization in solution. II. Specificity and
      cooperativity.
AB  - Because oligonucleotides are short sequences of nucleic acid bases, their
      association in solution with complementary strands (hybridization) is often seen
      to conform to a simple two-state model. However, experimental evidence suggests
      that, despite their short length, oligonucleotides may hybridize through multiple
      states involving intermediates. We investigate whether these apparently
      contradictory scenarios are possible by imposing different levels of sequence
      specificity on a lattice model of oligonucleotides in solution, which we
      introduced in Part I [J. C. Araque et al., J. Chem. Phys. 134, 165103 (2011)]. We
      find that both multiple-intermediate (weakly cooperative) and two-state (strongly
      cooperative) transitions are possible and that these are directly linked to the
      level of sequence specificity. Sequences with low specificity hybridize (base-by
      base) by way of multiple stable intermediates with increasing number of paired
      bases. Such intermediate states are weakly cooperative because the energetic gain
      from adding an additional base pair is outweighed by the conformational entropy
      loss. Instead, sequences with high specificity hybridize through multiple
      metastable intermediates which easily bridge the configurational and energetic
      gaps between single- and double-stranded states. These metastable intermediates
      interconvert with minimal loss of conformational entropy leading to a strongly
      cooperative hybridization. The possibility of both scenarios, multiple- and two
      states, is therefore encoded in the specificity of the sequence which in turn
      defines the level of cooperativity. 

PMID- 27036479
TI  - How nonspecifically DNA-binding proteins search for the target in crowded
      environments.
AB  - We investigate how a tracer particle searches a target located in DNA modeled by
      a stiff chain in crowded environments using theoretical analysis and Langevin
      dynamics simulations. First, we show that the three-dimensional (3D) diffusion
      coefficient of the tracer only depends on the density of crowders phi, while its
      one-dimensional (1D) diffusion coefficient is affected by not only phi but also
      the nonspecific binding energy epsilon. With increasing phi and epsilon, no
      obvious change in the average 3D diffusion time is observed, while the average 1D
      sliding time apparently increases. We propose theoretically that the 1D sliding
      of the tracer along the chain could be well captured by the Kramers' law of
      escaping rather than the Arrhenius law, which is verified directly by the
      simulations. Finally, the average search time increases monotonously with an
      increase in phi while it has a minimum as a function of epsilon, which could be
      understood from the different behaviors of the average number of search rounds
      with the increasing phi or epsilon. These results provide a deeper understanding
      of the role of facilitated diffusion in target search of proteins on DNA in vivo.

PMID- 27036480
TI  - A multi-pathway model for photosynthetic reaction center.
AB  - Charge separation occurs in a pair of tightly coupled chlorophylls at the heart
      of photosynthetic reaction centers of both plants and bacteria. Recently it has
      been shown that quantum coherence can, in principle, enhance the efficiency of a
      solar cell, working like a quantum heat engine. Here, we propose a biological
      quantum heat engine (BQHE) motivated by Photosystem II reaction center (PSII RC)
      to describe the charge separation. Our model mainly considers two charge
      separation pathways which is more than that typically considered in the published
      literature. We explore how these cross-couplings increase the current and power
      of the charge separation and discuss the effects of multiple pathways in terms of
      current and power. The robustness of the BQHE against the charge recombination in
      natural PSII RC and dephasing induced by environments is also explored, and
      extension from two pathways to multiple pathways is made. These results suggest
      that noise-induced quantum coherence helps to suppress the influence of acceptor
      to-donor charge recombination, and besides, nature-mimicking architectures with
      engineered multiple pathways for charge separations might be better for
      artificial solar energy devices considering the influence of environments. 

PMID- 27036481
TI  - Asynchronous tau-leaping.
AB  - Stochastic simulation of cell signaling pathways and genetic regulatory networks
      has contributed to the understanding of cell function; however, investigation of
      larger, more complicated systems requires computationally efficient algorithms.
      tau-leaping methods, which improve efficiency when some molecules have high copy
      numbers, either use a fixed leap size, which does not adapt to changing state, or
      recalculate leap size at a heavy computational cost. We present a hybrid
      simulation method for reaction-diffusion systems which combines exact stochastic
      simulation and tau-leaping in a dynamic way. Putative times of events are stored
      in a priority queue, which reduces the cost of each step of the simulation. For
      every reaction and diffusion channel at each step of the simulation the more
      efficient of an exact stochastic event or a tau-leap is chosen. This new approach
      removes the inherent trade-off between speed and accuracy in stiff systems which
      was present in all tau-leaping methods by allowing each reaction channel to
      proceed at its own pace. Both directions of reversible reactions and diffusion
      are combined in a single event, allowing bigger leaps to be taken. This improves
      efficiency for systems near equilibrium where forward and backward events are
      approximately equally frequent. Comparison with existing algorithms and behaviour
      for five test cases of varying complexity shows that the new method is almost as
      accurate as exact stochastic simulation, scales well for large systems, and for
      various problems can be significantly faster than tau-leaping. 

PMID- 27036482
TI  - Effects of monohydric alcohols and polyols on the thermal stability of a protein.
AB  - The thermal stability of a protein is lowered by the addition of a monohydric
      alcohol, and this effect becomes larger as the size of hydrophobic group in an
      alcohol molecule increases. By contrast, it is enhanced by the addition of a
      polyol possessing two or more hydroxyl groups per molecule, and this effect
      becomes larger as the number of hydroxyl groups increases. Here, we show that all
      of these experimental observations can be reproduced even in a quantitative sense
      by rigid-body models focused on the entropic effect originating from the
      translational displacement of solvent molecules. The solvent is either pure water
      or water-cosolvent solution. Three monohydric alcohols and five polyols are
      considered as cosolvents. In the rigid-body models, a protein is a fused hard
      spheres accounting for the polyatomic structure in the atomic detail, and the
      solvent is formed by hard spheres or a binary mixture of hard spheres with
      different diameters. The effective diameter of cosolvent molecules and the
      packing fractions of water and cosolvent, which are crucially important
      parameters, are carefully estimated using the experimental data of properties
      such as the density of solid crystal of cosolvent, parameters in the pertinent
      cosolvent-cosolvent interaction potential, and density of water-cosolvent
      solution. We employ the morphometric approach combined with the integral equation
      theory, which is best suited to the physical interpretation of the calculation
      result. It is argued that the degree of solvent crowding in the bulk is the key
      factor. When it is made more serious by the cosolvent addition, the solvent
      entropy gain upon protein folding is magnified, leading to the enhanced thermal
      stability. When it is made less serious, the opposite is true. The mechanism of
      the effects of monohydric alcohols and polyols is physically the same as that of
      sugars. However, when the rigid-body models are employed for the effect of urea,
      its addition is predicted to enhance the thermal stability, which conflicts with
      the experimental fact. We then propose, as two essential factors, not only the
      solvent-entropy gain but also the loss of protein-solvent interaction energy upon
      protein folding. The competition of changes in these two factors induced by the
      cosolvent addition determines the thermal-stability change. 

PMID- 27036483
TI  - Note: Sound velocity of a soft sphere model near the fluid-solid phase
      transition.
AB  - The quasilocalized charge approximation is applied to estimate the sound velocity
      of simple soft sphere fluid with the repulsive inverse-power-law interaction. The
      obtained results are discussed in the context of the sound velocity of the hard
      sphere system and of liquid metals at the melting temperature. 

PMID- 27036484
TI  - Erratum: "A kinetic approach to the theory of heterogeneous nucleation on soluble
      particles during the deliquescence stage" [J. Chem. Phys. 124, 194709 (2006)].

PMID- 27036485
TI  - Publisher's Note: "Nuclear spatial delocalization silences electron density
      oscillations in 2-phenyl-ethyl-amine (PEA) and 2-phenylethyl-N,N-dimethylamine
      (PENNA) cations" [J. Chem. Phys. 144, 104110 (2016)].

PMID- 27036486
TI  - Selenium inhibits Staphylococcus aureus-induced inflammation by suppressing the
      activation of the NF-kappaB and MAPK signalling pathways in RAW264.7 macrophages.
AB  - Inflammation is the hallmark of Staphylococcus aureus (S. aureus)-induced
      mastitis. Given the interesting relationship between selenium levels and
      inflammation, this study aimed to demonstrate that selenium modulated the
      inflammation reaction by suppressing the nuclear factor kappa B (NF-kappaB) and
      mitogen activated protein kinase (MAPK) signalling pathways. RAW264.7 macrophages
      were treated with three different concentrations (1MUmol/l, 1.5MUmol/l, and
      2MUmol/l) of Na2SeO3 for 12h before infection with S. aureus for 6h, 8h, and 10h.
      The results showed that selenium significantly reduced the mRNA expression levels
      of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and
      interleukin-6 (IL-6). Furthermore, the release of TNF-alpha, IL-1beta, and IL-6
      was decreased significantly with selenium supplementation. In addition, selenium
      influenced the NF-kappaB signalling pathway by suppressing the activation of NF
      kappaB p65 and degradation of inhibitory kappa-B (IkappaB). Selenium also
      suppressed extracellular regulated protein kinase (Erk), c-Jun N-terminal kinase
      (Jnk), and p38 phosphorylation through the MAPK signalling pathway. In
      conclusion, selenium played an anti-inflammation role in RAW264.7 macrophages
      infected with S. aureus by suppressing the activation of the NF-kappaB and MAPK
      signalling pathways. 

PMID- 27036487
TI  - Free light chains: potential biomarker and predictor of mortality in alpha-1
      antitrypsin deficiency and usual COPD.
AB  - BACKGROUND: Circulating free light chains (FLCs) can alter neutrophil migration,
      apoptosis and activation and may be a biomarker of autoimmune disease and
      adaptive immune system activation. These pathogenic roles could be relevant to
      lung disease in alpha 1 antitrypsin deficiency (A1ATD) and chronic obstructive
      pulmonary disease (COPD). METHODS: Total combined (c)FLCs were measured using the
      FreeLite(r) assay in 547 patients with A1ATD and 327 patients with usual COPD in
      the stable state, and assessed for association with clinical phenotype, disease
      severity, airway bacterial colonisation and mortality. Univariate and
      multivariate analyses were undertaken. RESULTS: Circulating cFLCs were static in
      the stable state when measured on 4 occasions in A1ATD and twice in usual COPD.
      Levels were inversely related to renal function (A1ATD and COPD p = <0.01), and
      higher in patients with chronic bronchitis (p = 0.019) and airway bacterial
      colonisation (p = 0.008). After adjusting for renal function and age the
      relationship between cFLCs and lung function was weak. Kaplan Meier curves showed
      that cFLC > normal (43.3 mg/L) significantly associated with mortality in both
      cohorts (A1ATD p = 0.001, COPD p = 0.013). CONCLUSIONS: cFLCs may be a promising
      biomarker for risk stratification in A1ATD and COPD.

PMID- 27036488
TI  - A novel cutoff for the waist-to-height ratio predicting metabolic syndrome in
      young American adults.
AB  - BACKGROUND: Recent studies have shown the enhanced diagnostic capability of the
      waist-to-height ratio (WHtR) over BMI. However, while a structured cutoff
      hierarchy has been established for BMI, a rigorous analysis to define individuals
      as obese using the WHtR has not been performed on a sample of American adults.
      This study attempts to establish a cutoff for the WHtR using metabolic syndrome
      as the outcome. METHODS: The study sample consisted of individuals that were part
      of the National Longitudinal Study of Adolescent Health (Add Health). The final
      sample for analysis consisted of 7 935 participants (3 469 males, 4 466 females)
      that were complete respondents for the variables of interest at Wave IV. The
      participants ranged from 24.55-33.60 years. Weighted and unweighted receiver
      operator characteristics (ROC) analyses were performed predicting metabolic
      syndrome from the WHtR. Cutoffs were chosen using the Youden index. The derived
      cutoffs were validated by logistic regression analysis on the Add Health
      participants and an external sample of 1 236 participants from the National
      Health and Nutrition Examination Survey (NHANES). RESULTS: The ROC analysis
      resulted in a WHtR cutoff of 0.578 (Youden Index = 0.50) for the full sample of
      complete respondents, 0.578 (Youden Index = 0.55) for males only, and 0.580
      (Youden Index = 0.50) for females only. The area under the curve was 0.798 (95%
      CI (0.788, 0.809)) for the full sample of complete respondents, 0.833 (95% CI
      (0.818, 0.848)) for males only, and 0.804 (95% CI (0.791, 0.818)) for females
      only. Participants in the validation sample with a WHtR greater than the derived
      cutoff were more likely (Odds Ratio = 9.8, 95% CI (6.2, 15.3)) to have metabolic
      syndrome than those that were not. CONCLUSION: A WHtR cutoff of 0.580 is optimal
      for discriminating individuals with metabolic syndrome in two nationally
      representative samples of young adults. This cutoff is an improvement over a
      previously recommended cutoff of 0.5 as well as other cutoffs derived from
      international samples.

PMID- 27036489
TI  - A household perspective on access to health care in the context of HIV and
      disability: a qualitative case study from Malawi.
AB  - BACKGROUND: Equitable access to health care is a challenge in many low-income
      countries. The most vulnerable segments of any population face increased
      challenges, as their vulnerability amplifies problems of the general population.
      This implies a heavy burden on informal care-givers in their immediate and
      extended households. However, research falls short of explaining the particular
      challenges experienced by these individuals and households. To build an evidence
      base from the ground, we present a single case study to explore and understand
      the individual experience, to honour what is distinctive about the story, but
      also to use the individual story to raise questions about the larger context.
      METHODS: We use a single qualitative case study approach to provide an in-depth,
      contextual and household perspective on barriers, facilitators, and consequences
      of care provided to persons with disability and HIV. RESULTS: The results from
      this study emphasise the burden that caring for an HIV positive and disabled
      family member places on an already impoverished household, and the need for
      support, not just for the HIV positive and disabled person, but for the entire
      household. CONCLUSIONS: Disability and HIV do not only affect the individual, but
      the whole household, immediate and extended. It is crucial to consider the
      interconnectedness of the challenges faced by an individual and a household.
      Issues of health (physical and mental), disability, employment, education,
      infrastructure (transport/terrain) and poverty are all related and
      interconnected, and should be addressed as a whole in order to secure equity in
      health.

PMID- 27036490
TI  - The Dynamicity of Steenbeek Foot Abduction Brace for Clubfoot in Dorsiflexion and
      Pronation: A Pilot Study.
AB  - PURPOSE: Steenbeek foot abduction brace (SFAB) has been widely used in various
      national clubfoot programs. The aim of the study was to define effectiveness and
      dynamicity of SFAB in terms of dorsiflexion and pronation for the corrected
      clubfoot. METHODS: Differences in foot dorsiflexion and pronation measurement
      with brace in knee flexed and extended position were recorded as dynamicity1 and
      dynamicity2, respectively. The residual soft tissue stretch lag despite brace use
      was calculated by determining the difference between maximum foot dorsiflexion
      (stretchlag1) and pronation (stretchlag2) achievable without and with brace in
      knee flexed. Statistical difference between measurements were calculated using
      paired t tests. RESULTS: There were a total of 63 feet in 40 patients. The mean
      foot dorsiflexion with brace on in knee extension was 7.57 degrees  and in
      flexion was 15.20 degrees . The foot pronation with brace on in knee extension
      was 9.46 degrees  and in flexion was 16.77 degrees . Thus, SFAB exerted
      statistically significant differences in foot dorsiflexion and pronation between
      the knee extended and flexed positions. Dynamicity1 and dynamicity2 were 7.63
      degrees  and 7.31 degrees , respectively. Stretchlag1 was 18.47 degrees  and
      stretchlag2 was 17.63 degrees . CONCLUSIONS: SFAB demonstrates effective
      dynamicity in maintaining corrected foot dorsiflexion and pronation. There is a
      residual soft tissue stretch lag both in dorsiflexion and pronation in corrected
      clubfoot despite use of SFAB. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case
      series.

PMID- 27036491
TI  - Contrast Therapy and Heat Therapy in Subacute Stage of Grade I and II Lateral
      Ankle Sprains.
AB  - Objective This study was conducted to determine the most effective thermal
      modality; heat or contrast therapy-in reducing pain, reducing swelling, and
      increasing range of movement (ROM) of the grade I and II lateral ankle sprain in
      the prechronic stage of the subacute phase. Design Randomized control trail.
      Methods One hundred and fifteen participants of both genders who were diagnosed
      as having grade I or II lateral ankle sprain were randomly assigned to the study
      on the fifth day of injury. Pain, volume, and ROM were recorded before and after
      treatment continuously for 3 days. Results Effects were evaluated as "Immediately
      after application" and "3 days after continuous application." Immediately after
      application, there was no difference between the 2 modalities on ankle ROM; heat
      reduced pain over contrast therapy, and both modalities increased swelling. When
      considering the effects after continuous application for 3 days, no difference
      was found between the 2 modalities on ROM and the reduction of pain. Contrast
      therapy reduced swelling while heat caused increased swelling even after 3 days.
      Conclusion The use of different thermal modalities during the transition from the
      acute to chronic phase of injury can be suggested as effective treatment options
      according to the objectives of injury management: pain reduction, improve ROM,
      and swelling management. LEVELS OF EVIDENCE: Therapeutic, Level II: Randomized
      clinical trial.

PMID- 27036492
TI  - Mucosal and salivary microbiota associated with recurrent aphthous stomatitis.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder
      of unclear etiopathogenesis. Although recent studies of the oral microbiota by
      high-throughput sequencing of 16S rRNA genes have suggested that imbalances in
      the oral microbiota may contribute to the etiopathogenesis of RAS, no specific
      bacterial species associated with RAS have been identified. The present study
      aimed to characterize the microbiota in the oral mucosa and saliva of RAS
      patients in comparison with control subjects at the species level. RESULTS: The
      bacterial communities of the oral mucosa and saliva from RAS patients with active
      lesions (RAS, n = 18 for mucosa and n = 8 for saliva) and control subjects (n =
      18 for mucosa and n = 7 for saliva) were analyzed by pyrosequencing of the 16S
      rRNA genes. There were no significant differences in the alpha diversity between
      the controls and the RAS, but the mucosal microbiota of the RAS patients showed
      increased inter-subject variability. A comparison of the relative abundance of
      each taxon revealed decreases in the members of healthy core microbiota but
      increases of rare species in the mucosal and salivary microbiota of RAS patients.
      Particularly, decreased Streptococcus salivarius and increased Acinetobacter
      johnsonii in the mucosa were associated with RAS risk. A dysbiosis index, which
      was developed using the relative abundance of A. johnsonii and S. salivarius and
      the regression coefficients, correctly predicted 83 % of the total cases for the
      absence or presence of RAS. Interestingly, A. johnsonii substantially inhibited
      the proliferation of gingival epithelial cells and showed greater cytotoxicity
      against the gingival epithelial cells than S. salivarius. CONCLUSION: RAS is
      associated with dysbiosis of the mucosal and salivary microbiota, and two species
      associated with RAS have been identified. This knowledge may provide a diagnostic
      tool and new targets for therapeutics for RAS.

PMID- 27036493
TI  - Effect of a nonthermal-atmospheric pressure plasma jet on wound healing: An
      animal study.
AB  - BACKGROUND: The use of a nonthermal plasma (NTP) jet in the treatment of living
      tissue has been the subject of considerable interest in the field of medical
      technology, and has the potential to reduce the recovery time of open wounds. We
      aimed to investigate the wound-healing process by clinical observation, blood
      tests, and expression of cell adhesion markers and reactive oxygen species in NTP
      jet-treated rats. METHODS: This study utilized Sprague-Dawley (SD) rats as
      experimental subjects, and wounds measuring 2 cm * 2 cm were produced on the
      animals' backs. The experimental group was treated with NTP for 5 min/d for 4
      weeks. The NTP was injected in a diffused manner into the cage housing the rats.
      The SD rats that had not received plasma treatment were designated as the control
      group. Blood was drawn on Postoperative Day 2, Day 4, and at 3 months. An
      immunohistochemical stain of E-cadherin and 4-hydroxy-2-nonenal (4-HNE), a
      reactive oxygen species marker, were evaluated and quantified for analysis using
      a CMYK color model. RESULTS: A total of 35 SD rats were included in the study (25
      in the NTP group and 10 in the control group). Low dose plasma treatment
      shortened the wound-healing time without damaging organs. In the NTP group, the
      white blood cell counts at Day 2 post-NTP treatment was not increased
      significantly more than that in the control group. After quantification of
      immunohistochemical staining, 4-HNE was increased at Day 14 compared with Day 7
      (16.16 +/- 12.81% vs. 55.11 +/- 8.11%, p < 0.001), and E-cadherin was also
      increased (52.17 +/- 14.96% vs. 70.46 +/- 12.78%, p = 0.04) in the NTP group.
      After comparison of NTP and the control, it was observed that 4-HNE and E
      cadherin were increased in the NTP group on Day 14. CONCLUSION: Short-term, low
      dose NTP wound treatment was demonstrated to accelerate wound healing in SD rats
      without vital organ toxicity.

PMID- 27036494
TI  - Radiation recall pneumonitis induced by epidermal growth factor receptor-tyrosine
      kinase inhibitor in patients with advanced nonsmall-cell lung cancer.
AB  - BACKGROUND: Radiation recall pneumonitis (RRP) is a special form of radiation
      pneumonitis precipitated by certain pharmacological agents. Epidermal growth
      factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is an effective treatment
      for advanced nonsmall-cell lung cancer (NSCLC) and has been reported as a potent
      radiation sensitizer. The incidence and general characteristics of EGFR-TKI
      related RRP in patients with NSCLC remain unclear. METHODS: Clinical records and
      serial chest images of consecutive patients with advanced NSCLC who had received
      thoracic radiotherapy (TRT) and EGFR-TKI treatment were retrospectively reviewed.
      EGFR-TKI-related RRP was diagnosed according to history, clinical manifestations,
      and radiographic characteristics. Potential risk factors were analyzed. RESULTS:
      In total, 160 patients with NSCLC who received EGFR-TKI after TRT were
      identified. Of these patients, seven (4.4%) developed EGFR-TKI-related RRP. The
      median time interval between the end of radiotherapy and RRP was 124 days (range,
      80-635 days) and that between the initiation of EGFR-TKI and RRP was 43 days
      (range, 18-65 days). No risk factor for the development of RRP was identified
      except that patients in whom EGFR-TKI was initiated within 90 days after the
      completion of radiotherapy had significantly higher rates of RRP than those of
      patients who began receiving EGFR-TKI treatment after 90 days (21% vs. 2.1%, p =
      0.005). CONCLUSION: In patients with NSCLC who have a history of TRT, treatment
      with EGFR-TKI may induce not only interstitial lung disease but also RRP.
      Physicians should be aware of both unexpected adverse events when using EGFR-TKI.

PMID- 27036495
TI  - The utilization of fluoride varnish and its determining factors among Taiwanese
      preschool children.
AB  - BACKGROUND: The Taiwanese government considers fluoride varnish to be a major
      component of preventive dental cares for preschool children. This study aimed to
      explore the extent of utilization of fluoride varnish and its determining factors
      among Taiwanese preschool children. METHODS: Using preschool children under the
      age of 5 years as our participants, this study was conducted based on the 2008
      Taiwan database of the Ministry of the Interior, linked with information gathered
      between 2006 and 2008 on preventive healthcare and health insurance from the
      Bureau of Health Promotion and the National Health Research Institute. A total of
      949,023 preschool children (< 5 years old) were identified to meet the
      requirement for fluoride varnish services. RESULTS: The percentage of Taiwanese
      preschool children that used fluoride varnish was 34.85%.The probability that
      fluoride varnish would be utilized was higher among children with catastrophic
      illness/injury or relevant chronic illnesses than those without. In addition, the
      probability of children with disabilities using fluoride varnish was lower than
      that of nondisabled children. Finally, parent sex, parent age, urbanization level
      of residence, and parents' premium-based salary significantly affected the
      children's utilization probability of fluoride varnish. CONCLUSION: In order to
      increase the utilization of fluoride varnish among preschool children in Taiwan
      in the future, target groups consisting of females, children < 3 years of age,
      and disabled children should be prioritized. Parental factors are also important
      in affecting the utilization of fluoride varnish in children.

PMID- 27036496
TI  - Intracranial aneurysms and optic glioma--an unusual combination: a case report.
AB  - BACKGROUND: The coexistence of glial high grade tumors (glioblastoma, anaplastic
      astrocytoma) and cerebral aneurysms is common but the association with optic
      glioma is rare. The treatment of these associated lesions is problematic. CASE
      PRESENTATION: A 36-year-old white woman presented to our institution with
      recurrent attacks of headache. Her preoperative radiological studies revealed a
      lesion of her left optic nerve with extension to the optic chiasma, an
      aneurysmatic dilatation of the left carotid bifurcation, a second aneurysm on the
      left of her middle cerebral artery, and a third one on her right anterior
      cerebral artery in the A2 tract. A left pterional approach was used to remove the
      tumor and clip the three aneurysmatic dilatations in a single stage. CONCLUSIONS:
      We report this unusual case of optic glioma associated to multiples aneurysms and
      review the pertinent literature. An adequate knowledge of this association is
      mandatory to plan the correct approach to avoid complications.

PMID- 27036497
TI  - Predicting the three-dimensional folding of cis-regulatory regions in mammalian
      genomes using bioinformatic data and polymer models.
AB  - The three-dimensional (3D) organization of chromosomes can be probed using
      methods like Capture-C. However, it is unclear how such population-level data
      relate to the organization within a single cell, and the mechanisms leading to
      the observed interactions are still largely obscure. We present a polymer
      modeling scheme based on the assumption that chromosome architecture is
      maintained by protein bridges, which form chromatin loops. To test the model, we
      perform FISH experiments and compare with Capture-C data. Starting merely from
      the locations of protein binding sites, our model accurately predicts the
      experimentally observed chromatin interactions, revealing a population of 3D
      conformations. 

PMID- 27036498
TI  - Specific expression and function of inositol 1,4,5-trisphosphate 3-kinase C
      (ITPKC) in wild type and knock-out mice.
AB  - Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of
      the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol
      1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate. Although expression
      and function of the two other family members ITPKA and ITPKB are rather well
      characterized, similar information is lacking for ITPKC. Here, we first defined
      the expression of Itpkc mRNA and protein in mouse tissues and cells using in situ
      hybridization and new antibodies. Surprisingly, we found that cells positive for
      ITPKC in the studied tissues express either a multicilium (tracheal and bronchial
      epithelia, brain ependymal cells), microvilli forming a brush border (small and
      large intestine, and kidney proximal tubule cells) or a flagellum (spermatozoa),
      suggesting a role for ITPKC either in the development or the function of these
      specialized cellular structures. Given this surprising expression, we then
      analyzed ITPKC function in multiciliated tracheal epithelial cells and sperm
      cells using our Itpkc knock-out mouse model. Unfortunately, no significant
      difference was observed between control and mutant mice for any of the parameters
      tested, leaving the exact in vivo function of this third Ins(1,4,5)P3 3-kinase
      still open.

PMID- 27036499
TI  - Are the Powerful Really Blind to the Feelings of Others? How Hierarchical
      Concerns Shape Attention to Emotions.
AB  - Paying attention to others' emotions is essential to successful social
      interactions. Integrating social-functional approaches to emotion with theorizing
      on the reciprocal nature of power, we propose that attention to others' emotions
      depends on concerns over one's power position and the social signal conveyed by
      the emotion. Others' anger signals attack-information relevant to high-power
      individuals who are concerned about the legitimacy or suitability of their
      position. On the contrary, others' fear signals vulnerability-information
      relevant to low-power individuals who are concerned about their unfair treatment
      within an illegitimate hierarchy. Accordingly, when power roles were
      illegitimately assigned or mismatched with one's trait power, leaders were faster
      at detecting the appearance of anger (Studies 1 and 2), slower at judging the
      disappearance of anger (Study 2), and more accurate in recognizing subordinates'
      anger, whereas subordinates were more accurate in recognizing leaders' fear
      (Study 3). Implications for theorizing about emotion and social hierarchy are
      discussed.

PMID- 27036500
TI  - Looking Out From the Top: Differential Effects of Status and Power on Perspective
      Taking.
AB  - The impact of hierarchical rank on perspective taking is both practically and
      theoretically important, prompting considerable research attention to this issue.
      However, prior research has primarily examined how power affects perspective
      taking, and has neglected to investigate the impact of status (i.e., the respect
      and esteem that an individual holds in the eyes of others). Yet status represents
      a distinct and ubiquitous basis of hierarchical differentiation, one that may
      profoundly affect perspective taking. The current research addresses this gap,
      theorizing and testing the prediction that high status enhances perspective
      taking, in contrast to prior research that has generally found that high power
      diminishes perspective taking. Five studies, examining various forms of
      perspective taking across diverse paradigms, provide converging evidence that
      status and power exert differential effects on perspective taking. Moreover,
      these studies provide insight regarding the distinction between status and power,
      as well as the distinct psychology associated with status.

PMID- 27036501
TI  - Increased precipitation of spasms in an animal model of infantile spasms by
      prenatal stress exposure.
AB  - Infantile spasms (IS) represent a serious epileptic syndrome, called West
      syndrome (WS) that occurs in the early infantile age. Although several hypotheses
      and animal models have been proposed to explain the pathogenesis of IS, the
      pathophysiology of IS has not been elucidated. Recently, we proposed a hypothesis
      for IS under prenatal stress exposure (also called Zou's hypothesis) by
      correlating diverse etiologies and prenatal stresses with IS development. This
      research aims to determine the mechanism through which prenatal stress affects
      the offspring and establish the potential underlying mechanisms. Pregnant rats
      were subjected to forced swimming in cold water. Rat pups exposed to prenatal
      stress were administered with N-methyl-D-aspartate (NMDA). Exposure to prenatal
      stress sensitized the rats against development of NMDA-induced spasms. However,
      this phenomenon was altered by administering adrenocorticotropin. Prenatal stress
      exposure also altered the hormonal levels and neurotransmitter receptor
      expression of the developing rats as well as influenced the tissue structure of
      the brain. These findings suggest that maternal stress could alter the level of
      endogenous glucocorticoid, which is the basis of IS, and cerebral dysplasia,
      hypoxic-ischemic encephalopathy (HIE), inherited metabolic diseases, and other
      factors activated this disease in developmental brain. 

PMID- 27036502
TI  - Generic RT-PCR tests for detection and identification of tospoviruses.
AB  - A set of tests for generic detection and identification of tospoviruses has been
      developed. Based on a multiple sequence alignment of the nucleocapsid gene and
      its 5' upstream untranslated region sequence from 28 different species, primers
      were designed for RT-PCR detection of tospoviruses from all recognized clades,
      i.e. the American, Asian and Eurasian clades, and from the small group of
      distinct and floating species. Pilot experiments on isolates from twenty
      different species showed that the designed primer sets successfully detected all
      species by RT-PCR, as confirmed by nucleotide sequence analysis of the amplicons.
      In a final optimized design, the primers were applied in a setting of five RT-PCR
      tests. Seven different tospoviruses were successfully identified from diagnostic
      samples and in addition a non-described tospovirus species from alstroemeria
      plants. The results demonstrate that the newly developed generic RT-PCR tests
      provide a relevant tool for broad detection and identification of tospoviruses in
      plant quarantine and diagnostic laboratories. 

PMID- 27036503
TI  - Immunological methods for the detection of porcine lymphotropic herpesviruses
      (PLHV).
AB  - Porcine lymphotropic herpesviruses (PLHV-1, -2, and -3) are widespread in pigs
      and closely related to the human pathogenic gammaherpesviruses Epstein-Barr virus
      (human herpesvirus 4, HHV-4) and Kaposi sarcoma herpesvirus (HHV-8). In minipigs,
      PLHV-1 causes a porcine post-transplantation lymphoproliferative disorder (PTLD)
      after experimental transplantations. Porcine PTLD comes with clinical symptoms
      similar to those of human PTLD, a serious complication of solid organ and
      allogeneic bone marrow transplantation linked to HHV-4. Since PLHVs may be
      transmitted from donor pigs to the human recipient of xenotransplants (pig cells,
      tissues or organs), sensitive and specific methods should be developed to detect
      and eliminate PLHVs. Here we describe an ELISA and a Western blot assay using
      recombinant glycoprotein B of PLHV-1. Using both assays, the presence of specific
      antibodies in different pig breeds as well as in German slaughterhouse workers
      was analysed. Antibodies were detected in some animals, but not in human
      subjects. 

PMID- 27036504
TI  - Development and evaluation of a reverse transcription-insulated isothermal
      polymerase chain reaction (RT-iiPCR) assay for detection of equine arteritis
      virus in equine semen and tissue samples using the POCKITTM system.
AB  - Equine arteritis virus (EAV) is the causative agent of equine viral arteritis
      (EVA), a respiratory and reproductive disease of horses. Most importantly, EAV
      induces abortion in pregnant mares and can establish persistent infection in up
      to 10-70% of the infected stallions, which will continue to shed the virus in
      their semen. The objective of this study was to develop and evaluate a reverse
      transcription insulated isothermal polymerase chain reaction (RT-iiPCR) for the
      detection of EAV in semen and tissue samples. The newly developed assay had a
      limit of detection of 10 RNA copies and a 10-fold higher sensitivity than a
      previously described real-time RT-PCR (RT-qPCR). Evaluation of 125 semen samples
      revealed a sensitivity and specificity of 98.46% and 100.00%, respectively for
      the RT-qPCR assay, and 100.00% and 98.33%, respectively for the RT-iiPCR assay.
      Both assays had the same accuracy (99.2%, k=0.98) compared to virus isolation.
      Corresponding values derived from testing various tissue samples (n=122)
      collected from aborted fetuses, foals, and EAV carrier stallions are as follows:
      relative sensitivity, specificity, and accuracy of 88.14%, 96.83%, and 92.62%
      (k=0.85), respectively for the RT-qPCR assay, and 98.31%, 92.06%, and 95.08%
      (k=0.90), respectively for the RT-iiPCR assay. These results indicate that RT
      iiPCR is a sensitive, specific, and a robust test enabling detection of EAV in
      semen and tissue samples with very considerable accuracy. Even though the RT-qPCR
      assay showed a sensitivity and specificity equal to virus isolation for semen
      samples, its diagnostic performance was somewhat limited for tissue samples.
      Thus, this new RT-iiPCR could be considered as an alternative tool in the
      implementation of EAV control and prevention strategies.

PMID- 27036505
TI  - isomiR-SEA: an RNA-Seq analysis tool for miRNAs/isomiRs expression level
      profiling and miRNA-mRNA interaction sites evaluation.
AB  - BACKGROUND: Massive parallel sequencing of transcriptomes, revealed the presence
      of many miRNAs and miRNAs variants named isomiRs with a potential role in several
      cellular processes through their interaction with a target mRNA. Many methods and
      tools have been recently devised to detect and quantify miRNAs from sequencing
      data. However, all of them are implemented on top of general purpose alignment
      methods, thus providing poorly accurate results and no information concerning
      isomiRs and conserved miRNA-mRNA interaction sites. RESULTS: To overcome these
      limitations we present a novel algorithm named isomiR-SEA, that is able to
      provide users with very accurate miRNAs expression levels and both isomiRs and
      miRNA-mRNA interaction sites precise classifications. Tags are mapped on the
      known miRNAs sequences thanks to a specialized alignment algorithm developed on
      top of biological evidence concerning miRNAs structure. Specifically, isomiR-SEA
      checks for miRNA seed presence in the input tags and evaluates, during all the
      alignment phases, the positions of the encountered mismatches, thus allowing to
      distinguish among the different isomiRs and conserved miRNA-mRNA interaction
      sites. CONCLUSIONS: isomiR-SEA performances have been assessed on two public RNA
      Seq datasets proving that the implemented algorithm is able to account for more
      reliable and accurate miRNAs expression levels with respect to those provided by
      two compared state of the art tools. Moreover, differently from the few methods
      currently available to perform isomiRs detection, the proposed algorithm
      implements the evaluation of isomiRs and conserved miRNA-mRNA interaction sites
      already in the first alignment phases, thus avoiding any additional filtering
      stages potentially responsible for the loss of useful information.

PMID- 27036506
TI  - Trends in Use of Medications for Smoking Cessation in Medicare, 2007-2012.
AB  - INTRODUCTION: Smoking-related disease accounts for 10% of Medicare expenditures.
      Although clinical guidelines recommend smoking-cessation medications, they are
      subject to safety warnings from the U.S. Food and Drug Administration (FDA). This
      study investigated trends in utilization of smoking-cessation medications in
      Medicare from 2007 to 2012. METHODS: Data on medical claims and prescription
      drugs for a nationally representative sample of Medicare beneficiaries were used
      to study trends from 2007 to 2012 in use of smoking-cessation medications
      (bupropion, nicotine-replacement therapy, varenicline), among beneficiaries who
      used tobacco (N=205,675). Analyses were conducted in 2015. Multinomial logistic
      regression was used to examine differences in use of bupropion, nicotine
      replacement therapy, varenicline, or more than one medication, relative to none,
      by beneficiaries' health and demographic characteristics. Binary logistic
      regression calculated average predicted probabilities of cardiovascular disease
      or depression among medication users before and after FDA safety warnings related
      to those conditions. RESULTS: Sixteen percent of tobacco users ever filled a
      prescription for a smoking-cessation medication. The proportion of beneficiaries
      who filled prescriptions for varenicline increased in 2007 but sharply declined
      corresponding to public warnings about adverse effects, although the same trends
      did not occur for bupropion or nicotine-replacement therapy. After FDA safety
      concerns were published, the average predicted probability of beneficiaries
      filling varenicline prescriptions with cardiovascular disease declined by 31%,
      although the average predicted probability of depression did not decline.
      CONCLUSIONS: Use of smoking-cessation medications among Medicare beneficiaries
      remains low. Health effects of Medicare policies that increase coverage for
      medical support for smoking cessation may be limited by low utilization of
      effective medications.

PMID- 27036507
TI  - Transplantar intramedullary locking nailing in childhood congenital
      pseudarthrosis of the tibia: A report of 3 cases.
AB  - The treatment objectives in congenital pseudarthrosis of the tibia are bone
      consolidation and a restored lower-limb axis. They are difficult to achieve, and
      various surgical techniques have been described, with varying results in terms of
      bone consolidation and complications. The present study reports clinical and
      radiographic results in 3 patients managed by the same original technique of
      transplantar intramedullary nailing using a custom-made proximal locking nail,
      without surgical approach or resection of the pseudarthrosis site. Good assembly
      stability allowed immediate weight-bearing. The technique is relatively
      noninvasive, offering a first-line alternative in under-3 year-olds.

PMID- 27036508
TI  - Lateral band translocation for swan-neck deformity: Outcomes of 41 digits after a
      mean follow-up of eight years.
AB  - BACKGROUND: Swan-neck deformity (SND) of the fingers can cause major functional
      impairment. The Zancolli-Tonkin procedure is a crossed dynamic tenodesis that
      prevents overextension of the proximal interphalangeal (PIP) joint and promotes
      extension of the distal interphalangeal (DIP) joint. We assessed the outcomes of
      this procedure in patients with SND due to various causes. HYPOTHESIS: The
      Zancolli-Tonkin procedure provides effective and stable correction of SND due not
      only to RA, but also to other conditions. PATIENTS AND METHODS: Consecutive
      patients managed at two centres between 2000 and 2013 were included. The causes
      of SND were inflammatory joint disease, trauma, iatrogenic events, and
      neurological disorders. The same operative technique was used in all patients.
      RESULTS: Forty-one fingers in 14 patients were evaluated. After a mean follow-up
      of 8 years, all patients could harmoniously flex the operated fingers and none
      had recurrence of the deformity. At the PIP joints, mean active flexion was 86
      degrees  (range: 40 degrees -90 degrees ) and mean loss of extension was 15
      degrees  (range: 0 degrees -40 degrees ). At the DIP joints, mean active flexion
      was 65 degrees  (range: 0 degrees -70 degrees ) and mean extension lag was 4
      degrees  (range: 0 degrees -30 degrees ). The mean visual analogue scale pain
      score was 1/10 (range: 0/10-8/10) and the mean patient satisfaction score was
      7.5/10 (range: 4/10-10/10). DISCUSSION: The SND was corrected and the results
      were stable after 8 years in all cases. Advantages of the Zancolli-Tonkin
      procedure include limited invasiveness, with no need to harvest a distant tendon,
      and rapid active postoperative rehabilitation. The moderate excessive PIP joint
      flexion has no adverse impact on the overall functional outcome. The high level
      of patient satisfaction reflects the improvements in function. CONCLUSION: The
      Zancolli-Tonkin procedure is a simple and reliable technique that provides
      lasting correction of an incapacitating deformity associated with impaired
      overall hand function. LEVEL OF EVIDENCE: IV.

PMID- 27036509
TI  - W Chromosome Dynamics in Triportheus Species (Characiformes, Triportheidae): An
      Ongoing Process Narrated by Repetitive Sequences.
AB  - Characterizing the abundance and genomic distribution of repetitive DNAs provides
      information on genome evolution, especially regarding the origin and
      differentiation of sex chromosomes. Triportheus fishes offer a useful model to
      explore the evolution of sex chromosomes, since they represent a monophyletic
      group in which all species share a ZZ/ZW sex chromosome system. In this study, we
      analyzed the distribution of 13 classes of repetitive DNA sequences by FISH,
      including microsatellites, rDNAs, and transposable elements in 6 Triportheus
      species, in order to investigate the fate of the sex-specific chromosome among
      them. These findings show the dynamic differentiation process of the W chromosome
      concerning changes in the repetitive DNA fraction of the heterochromatin. The
      differential accumulation of the same class of repeats on this chromosome, in
      both nearby and distant species, reflects the inherent dynamism of the
      microsatellites, as well as the plasticity that shapes the evolutionary history
      of the sex chromosomes, even among closely related species sharing a same sex
      chromosome system.

PMID- 27036510
TI  - Status of vaccine research and development for norovirus.
AB  - The global health community is beginning to gain an understanding of the global
      burden of norovirus-associated disease, which appears to have significant burden
      in both developed- and developing-country populations. Of particular importance
      is the growing recognition of norovirus as a leading cause of gastroenteritis and
      diarrhea in countries where rotavirus vaccine has been introduced. While not as
      severe as rotavirus disease, the sheer number of norovirus infections not limited
      to early childhood makes norovirus a formidable global health problem. This
      article provides a landscape review of norovirus vaccine development efforts.
      Multiple vaccine strategies, mostly relying on virus-like particle antigens, are
      under development and have demonstrated proof of efficacy in human challenge
      studies. Several are entering phase 2 clinical development. Norovirus vaccine
      development challenges include, but are not limited to: valency, induction of
      adequate immune responses in pediatric and elderly populations, and potential for
      vaccine-strain mismatch. Given current strategies and global health interest, the
      outlook for a norovirus vaccine is promising. Because a norovirus vaccine is
      expected to have a dual market in both developed and developing countries, there
      would likely be scale-up advantages for commercial development and global
      distribution. Combination with or expression by another enteric pathogen, such as
      rotavirus, could also enhance uptake of a norovirus vaccine.

PMID- 27036511
TI  - Advancing a vaccine to prevent human schistosomiasis.
AB  - Several candidate human schistosomiasis vaccines are in different stages of
      preclinical and clinical development. The major targets are Schistosoma
      haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal
      schistosomiasis) that account for 99% of the world's 252 million cases, with 90%
      of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm
      14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non
      human primates. Sh28GST, also known as Bilhvax is in advanced clinical
      development for S. haematobium infection. The possibility remains that some of
      these vaccines may cross-react to target both schistosome species. These vaccines
      were selected on the basis of their protective immunity in preclinical challenge
      models, through human immune-epidemiological studies or both. They are being
      advanced through a combination of academic research institutions, non-profit
      vaccine product development partnerships, biotechnology companies, and developing
      country vaccine manufacturers. In addition, new schistosome candidate vaccines
      are being identified through bioinformatics, OMICs approaches, and moderate
      throughput screening, although the full potential of reverse vaccinology for
      schistosomiasis has not yet been realized. The target product profiles of these
      vaccines vary but many focus on vaccinating children, in some cases following
      mass treatment with praziquantel, also known as vaccine-linked chemotherapy.
      Several regulatory pathways have been proposed, some of which rely on World
      Health Organization prequalification.

PMID- 27036512
TI  - Stunting correlates with high salivary and serum antibody levels after 13-valent
      pneumococcal conjugate vaccination of Venezuelan Amerindian children.
AB  - OBJECTIVE: To determine the impact of pre-vaccination nutritional status on
      vaccine responses in Venezuelan Warao Amerindian children vaccinated with the 13
      valent pneumococcal conjugate vaccine (PCV13) and to investigate whether saliva
      can be used as read-out for these vaccine responses. METHODS: A cross-sectional
      cohort of 504 Venezuelan Warao children aged 6 weeks - 59 months residing in nine
      geographically isolated Warao communities were vaccinated with a primary series
      of PCV13 according to Centers for Disease Control and Prevention (CDC)
      recommended age-related schedules. Post-vaccination antibody concentrations in
      serum and saliva of 411 children were measured by multiplex immunoassay. The
      influence of malnutrition present upon vaccination on post-vaccination antibody
      levels was assessed by univariate and multivariable generalized estimating
      equations linear regression analysis. RESULTS: In both stunted (38%) and non
      stunted (62%) children, salivary antibody concentrations correlated well with
      serum levels for all serotypes with coefficients varying from 0.61 for serotype 3
      0.80 for serotypes 5, 6A and 23F (all p < 0.01). Surprisingly, higher serum and
      salivary antibody levels were observed with increasing levels of stunting in
      children for all serotypes. This was statistically significant for 5/13 and 11/13
      serotype-specific serum and saliva IgG concentrations respectively. CONCLUSION:
      Stunted Amerindian children showed generally higher antibody concentrations than
      well-nourished children following PCV13 vaccination, indicating that chronic
      malnutrition influences vaccine response. Saliva samples might be useful to
      monitor serotype-specific antibody levels induced by PCV vaccination. This would
      greatly facilitate studies of vaccine efficacy in rural settings, since
      participant resistance generally hampers blood drawing.

PMID- 27036513
TI  - Immunopathologic characterization of ultrasound-defined synovitis in rheumatoid
      arthritis patients in clinical remission.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) in clinical remission may
      have ultrasound-defined synovitis according to the presence of power Doppler (PD)
      signal. The objective was to describe the immunopathologic characteristics of
      ultrasound-defined synovitis compared with synovitis in patients with clinically
      active RA. METHODS: We included between 6 and 8 ultrasound-guided synovial
      biopsies per patient from 20 patients with RA in clinical remission (DAS28-ESR
      <2.6) with PD signal, 22 synovial tissue samples (ST) from patients with
      clinically active RA (swollen joint with confirmed inflammatory synovial fluid)
      as inflammatory controls, and 10 ST from non-inflammatory controls.
      Immunostaining for CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages),
      CD117 (mast cells), hsp47 (fibroblasts), bFGF and CXCL12 (angiogenic factors) was
      made and quantified by digital image analysis. The number of CD31 vessels/mm(2)
      was quantified. RESULTS: RA patients in remission with PD signal had
      significantly reduced synovial T-cell, B-cell, mast cell and fibroblast density,
      but similar macrophage infiltration compared with patients with clinically active
      RA. Vascularity, bFGF and CXCL12 were partially reduced in RA patients in
      remission with PD signal compared to those with active RA, but were significantly
      higher compared with ST from non-inflammatory controls. During the 12-month
      follow up, 8/20 RA patients (40 %) lost remission: all had synovial hypertrophy
      grade >=2 and significantly more synovial B cells and mast cells than patients
      maintaining remission. CONCLUSIONS: Asymptomatic ultrasound-defined synovitis and
      clinically active arthritis differ in the degree of infiltrating lymphoid, mast
      cells and fibroblast density, but are similar with respect to macrophage
      infiltration. Persistently increased angiogenic factor expression and vascularity
      may explain the persistence of a PD signal.

PMID- 27036514
TI  - Functional and genetic screening of acute myeloid leukemia associated with
      mediastinal germ cell tumor identifies MEK inhibitor as an active clinical agent.
AB  - BACKGROUND: Hematologic malignancies arising in the setting of established germ
      cell tumors have been previously described and have a dismal prognosis.
      Identification of targetable mutations and pathway dysregulation through
      massively parallel sequencing and functional assays provides new approaches to
      disease management. CASE PRESENTATION: Herein, we report the case of a 23-year
      old male who was diagnosed with a mediastinal germ cell tumor and subsequent
      acute myeloid leukemia. A shared clonal origin was demonstrated through
      identification of identical NRAS and TP53 somatic mutations in both malignancies.
      The patient's leukemia was refractory to standard therapies with short interval
      relapse. Functional assays demonstrated the patient's blasts to be sensitive to
      the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib,
      correlating with the activating NRAS mutation. The patient experienced a
      sustained partial remission while on trametinib therapy but ultimately suffered
      relapse of the germ cell tumor. The leukemic clone remained stable and sensitive
      to trametinib at that time. CONCLUSIONS: This case highlights the potential power
      of combining genetic sequencing and in vitro functional assays with targeted
      therapies in the treatment of rare diseases.

PMID- 27036515
TI  - Does the addition of virtual reality training to a standard program of inpatient
      rehabilitation improve sitting balance ability and function after stroke?
      Protocol for a single-blind randomized controlled trial.
AB  - BACKGROUND: Sitting ability and function are commonly impaired after stroke.
      Balance training has been shown to be helpful, but abundant repetitions are
      required for optimal recovery and patients must be motivated to perform
      rehabilitation exercises repeatedly to maximize treatment intensity. Virtual
      reality training (VRT), which allows patients to interact with a virtual
      environment using computer software and hardware, is enjoyable and may encourage
      greater repetition of therapeutic exercises. However, the potential for VRT to
      promote sitting balance has not yet been explored. The objective of this study is
      to determine if supplemental VRT-based sitting balance exercises improve sitting
      balance ability and function in stroke rehabilitation inpatients. METHODS/DESIGN:
      This is a single-site, single-blind, parallel-group randomized control trial.
      Seventy six stroke rehabilitation inpatients who cannot stand independently for
      greater than one minute but can sit for at least 20 minutes (including at least
      one minute without support) are being recruited from a tertiary-care dedicated
      stroke rehabilitation unit. Participants are randomly allocated to experimental
      or control groups. Both participate in 10-12 sessions of 30-45 minutes of VRT
      performed in sitting administered by a single physiotherapist, in addition to
      their traditional therapy. The experimental group plays five games which
      challenge sitting balance while the control group plays five games which minimize
      trunk lean. Outcome measures of sitting balance ability (Function in Sitting
      Test, Ottawa Sitting Scale, quantitative measures of postural sway) and function
      (Reaching Performance Scale, Wolf Motor Function Test, quantitative measures of
      the limits of stability) are administered prior to, immediately following, and
      one month following the intervention by a second physiotherapist blind to the
      participant's group allocation. DISCUSSION: The treatment of sitting balance post
      stroke with VRT has not yet been explored. Results from the current study will
      provide important evidence for the use of low-cost, accessible VRT as an adjunct
      intervention to increase sitting balance in lower-functioning patients receiving
      inpatient rehabilitation. The motivating and enjoyable attributes of VRT may
      increase exercise dosage, leading to improved function and optimal results from
      rehabilitation. TRIAL REGISTRATION: https://clinicaltrials.gov/; Identifier:
      NCT02285933. Registered 06 November 2014. Funded by the Heart & Stroke Foundation
      of Canada and a generous donation from Tony & Elizabeth Graham.

PMID- 27036516
TI  - Protecting health workers from infectious disease transmission: an exploration of
      a Canadian-South African partnership of partnerships.
AB  - BACKGROUND: Health workers are at high risk of acquiring infectious diseases at
      work, especially in low and middle-income countries (LMIC) with critical health
      human resource deficiencies and limited implementation of occupational health and
      infection control measures. Amidst increasing interest in international
      partnerships to address such issues, how best to develop such collaborations is
      being actively debated. In 2006, a partnership developed between occupational
      health and infection control experts in Canada and institutions in South Africa
      (including an institute with a national mandate to conduct research and provide
      guidance to protect health workers from infectious diseases and promote improved
      working conditions). This article describes the collaboration, analyzes the
      determinants of success and shares lessons learned. METHODS: Synthesizing
      participant-observer experience from over 9 years of collaboration and 10 studies
      already published from this work, we applied a realist review analysis to
      describe the various achievements at global, national, provincial and hospital
      levels. Expectations of the various parties on developing new insights, providing
      training, and addressing service needs were examined through a micro-meso-macro
      lens, focusing on how each main partner organization contributed to and
      benefitted from working together. RESULTS: A state-of-the-art occupational health
      and safety surveillance program was established in South Africa following
      successful technology transfer from a similar undertaking in Canada and training
      was conducted that synergistically benefitted Northern as well as Southern
      trainees. Integrated policies combining infection control and occupational health
      to prevent and control infectious disease transmission among health workers were
      also launched. Having a national (South-South) network reinforced by the
      international (North-south) partnership was pivotal in mitigating the challenges
      that emerged. CONCLUSIONS: High-income country partnerships with experience in
      health system strengthening - particularly in much needed areas such as
      occupational health and infection control - can effectively work through strong
      collaborators in the Global South to build capacity. Partnerships are
      particularly well positioned to sustainably reinforce efforts at national and sub
      national LMIC levels when they adopt a "communities of practice" model,
      characterized by multi-directional learning. The principles of effective
      collaboration learned in this "partnership of partnerships" to improve working
      conditions for health workers can be applied to other areas where health system
      strengthening is needed.

PMID- 27036517
TI  - Erratum to: The accuracy and timeliness of a Point Of Care lactate measurement in
      patients with Sepsis.

PMID- 27036518
TI  - Preoperative Prediction and Postoperative Surgeon Assessment of Volume
      Preservation Associated With Partial Nephrectomy: Comparison With Measured Volume
      Preservation.
AB  - OBJECTIVE: To evaluate whether surgeons can predict the percent parenchymal mass
      that will be preserved by partial nephrectomy (PN) based on preoperative imaging,
      which could have potential utility for preoperative surgical planning and patient
      counseling. The proportion of preserved viable parenchyma following PN is the
      primary determinant of functional recovery. However, direct measurement of
      parenchymal volume preservation (VP) can be complex and time consuming. MATERIALS
      AND METHODS: For patients managed with PN at our institution (2007-2014), we
      randomly selected 45 with a third in each of low, intermediate, or high
      R.E.N.A.L. complexity groups. All patients had recorded postoperative surgeon
      assessment of volume preservation (SAVP) and measured VP based on preoperative or
      postoperative computed tomography. Nine clinical providers predicted VP based
      solely on review of preoperative imaging while blinded to SAVP and measured VP.
      Clinical experience of the providers ranged from medical students to experienced
      urologic surgeons. RESULTS: Median age was 66 years, median tumor size was 4.0
      cm, and median R.E.N.A.L. was 8. Median measured VP was 81% (interquartile range
      of 74-89%). Preoperative prediction of VP correlated poorly with measured VP
      among the different surgeons (mean correlation coefficient, R = 0.34, range =
      0.24-0.40). Surgeon experience provided minimal incremental improvement.
      Correlation between R.E.N.A.L. and measured VP was also marginal (R = 0.43). In
      contrast, correlation between postoperative SAVP and measured VP was much more
      robust (R = 0.75, P <.001). CONCLUSION: Preoperative prediction of VP and
      R.E.N.A.L. score correlated poorly with measured VP for patients managed with PN.
      In contrast, postoperative SAVP provided a relatively reliable estimate of VP,
      and should be considered an acceptable substitute in most clinical circumstances.

PMID- 27036519
TI  - Autologous Transobturator Urethral Sling Placement for Female Stress Urinary
      Incontinence: Short-term Outcomes.
AB  - OBJECTIVE: To evaluate short-term outcomes of autologous transobturator (ATO)
      urethral sling placement using rectus fascia for female stress urinary
      incontinence. MATERIALS AND METHODS: We evaluated the outcomes of 33 consecutive
      females who underwent ATO sling placement with rectus fascia for stress
      incontinence from 2013 to 2014. Patients were seen at 3 months postoperatively
      and mailed a questionnaire at least 1 year after surgery for further follow-up.
      Outcomes were measured by the International Consultation on Incontinence
      Questionnaire Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) score and compared
      between pre- and postoperative responses using Wilcoxon signed-rank test.
      Retreatment-free survival rates were evaluated via Kaplan-Meier method. RESULTS:
      Median patient age was 62 years old (interquartile range [IQR] 47.5; 70.5) with a
      median body mass index of 28.6 kg/m(2) (IQR 24.7 kg/m(2); 32.4 kg/m(2)). When
      isolated sling placement was performed, 88% (15/17) were outpatient procedures.
      Median follow-up was 14.9 months (IQR 3.6; 18.7), during which 5 patients
      underwent repeat anti-incontinence surgery. For those without retreatment, 25/28
      (89%) completed ICIQ-FLUTS at last follow-up. Compared to preoperative scores,
      patients who completed ICIQ-FLUTS questionnaires at 1 year or greater (N = 18)
      showed significant improvement in all domains: frequency (P = .007), voiding (P =
      .02), and incontinence (P = .004), and in quality of life related to frequency (P
      = .008), voiding (P = .002) and incontinence (P = .01). Among those who completed
      questionnaires both at 3 months and at least 1 year after surgery (N = 17), there
      was no significant deterioration in ICIQ-FLUTS scores. Overall retreatment-free
      survival rate was 92% at 1 year. Notably, no patients suffered severe (Clavien
      III-V) complications or required sling release. CONCLUSION: ATO urethral sling
      placement appears safe, with promising short-term outcomes. Longer follow-up and
      external validation are needed.

PMID- 27036520
TI  - Synthesis and biological evaluation of 2-arylimino-3-pyridin-thiazolineone
      derivatives as antibacterial agents.
AB  - With an intention to find more potent antibacterial agents, four halogen
      disubstituted thiazolineone derivatives (2a-d), five halogen monosubstituted
      thiazolineone derivatives (2e-i), and eleven 2-arylimino-3-pyridin-thiazolineone
      derivatives (2j-t) were synthesized and screened for their antibacterial
      activity, bactericidal activity, cytotoxicity, and erythrocyte hemolysis. Most of
      the synthesized derivatives showed antibacterial activity in inhibiting the
      growth of S. epidermidis and MRSA, and exhibited safety in the cytotoxicity study
      on the Vero cells and hemolytic activities test on healthy human erythrocytes. 2
      Arylimino-3-pyridin-thiazolineone derivatives not only improved the clog P, but
      also showed potent antibacterial activity in inhibiting the growth of S.
      epidermidis and MRSA. In particularly, several compounds (2f, 2i, 2r and 2t)
      showed bactericidal activity, in which compound 2r displayed the best inhibitory
      capacity among the synthesized compounds, and further druggability research is on
      going.

PMID- 27036521
TI  - Iodine catalyzed simple and efficient synthesis of antiproliferative 2-pyridones.
AB  - A simple and efficient method for the selective synthesis of 2-pyrdones from 4H
      pyrans using iodine as catalyst and ethanol as solvent was developed. The present
      method is equally effective for both aromatic and hetero aromatic ring containing
      4H-pyrans. The compatibility with various functional groups, mild reaction
      conditions, high yields and application of inexpensive, readily and easily
      available iodine as catalyst and formation of 2-pyridones as major products are
      the advantages of the present procedure. In vitro antiproliferative activity of
      the final synthesized compounds was evaluated with four different human cancer
      cell lines (Lung adenocarcinoma-A549, Hepatocarcinoma-HepG2, Breast carcinoma-MCF
      7 and Ovarian carcinoma-SKOV3) and normal human lung fibroblast cell line (MRC
      5). Compounds 2b showed better inhibition against MCF-7, HepG2 and A549 cell
      lines (IC50 8.00 +/- 0.11, 11.93 +/- 0.01 and 15.85 +/- 0.04 MUM, respectively)
      as compared with doxorubicin and also 2e showed moderate inhibition against MCF
      7, HepG2 (IC50 9.32 +/- 0.21 and 20.22 +/- 0.01 MUM, respectively, cell lines,
      respectively) as compared with doxorubicin. As many clinically used
      antiproliferative agents induce apoptosis in cancer cells hence, the 2-pyridone
      analogues were also tested for their ability to induce apoptosis in MCF-7 cells
      using the caspases-3 and -9 assays.

PMID- 27036522
TI  - Strigolactone derivatives for potential crop enhancement applications.
AB  - New technologies able to mitigate the main abiotic stresses (i.e., drought,
      salinity, cold and heat) represent a substantial opportunity to contribute to a
      sustainable increase of agricultural production. In this context, the recently
      discovered phytohormone strigolactone is an important area of study which can
      underpin the quest for new anti-stress technologies. The pleiotropic roles played
      by strigolactones in plant growth/development and in plant adaptation to
      environmental changes can pave the way for new innovative crop enhancement
      applications. Although a significant scientific effort has been dedicated to the
      strigolactone subject, an updated review with emphasis on the crop protection
      perspective was missing. This paper aims to analyze the advancement in different
      areas of the strigolactone domain and the implications for agronomical
      applications.

PMID- 27036527
TI  - Definitive host influences the proteomic profile of excretory/secretory products
      of the trematode Echinostoma caproni.
AB  - BACKGROUND: Echinostoma caproni is an intestinal trematode extensively used as
      experimental model for the study of factors that determine the course of
      intestinal helminth infections, since this markedly depends on the host species.
      Although the host-dependent mechanisms for either chronic establishment or early
      parasite rejection have been broadly studied, little is known regarding the
      parasite response against different host environments. METHODS: To identify host
      dependent differentially expressed proteins, a comparative proteomic analysis of
      the excretory/secretory products released from E. caproni adults, isolated from
      hosts displaying different compatibility with this trematode, was performed.
      RESULTS: A total of 19 differential protein spots were identified (14
      overexpressed in mice and 5 overexpressed in rats). The establishment of chronic
      infections in mice is mainly associated with the overexpression by adult worms of
      antioxidant and detoxifying enzymes (e.g. glutathione S-transferase,
      hydroxyacylglutathione hydrolase, thiopurine S-transferase, etc.) and metabolic
      enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However,
      the overexpression of cathepsin L and the structural protein actin observed in
      worms isolated from rats seems not to be effective for the colonization of the
      intestinal mucosa of this host. CONCLUSIONS: The observed differences suggest
      that protein expression and/or release is modulated by the local environment
      generated inside the host and provide useful insights in regards to the
      resistance mechanisms developed by parasites to ensure their long-term survival.

PMID- 27036528
TI  - Eyelid reconstruction in a child with xeroderma pigmentosum.
AB  - CLINICAL CASE: Seven-year-old male patient, affected by xeroderma pigmentosum
      (XP) who was referred to ophthalmology due to the presence of numerous tumours in
      his left eye that affected the eyelids and conjunctiva. He had a tumour in his
      lower eyelid that affected the free edge, creating a secondary ectropion, and
      several lesions with a melanocytic appearance in conjunctiva. A resection of the
      eyelid tumour and the conjunctival lesions were performed by placing a skin graft
      and amniotic membrane, respectively, as covering. DISCUSSION: XP patients have
      high probability of developing eye tumours. A thorough ophthalmic examination is
      necessary to establish an early diagnosis.

PMID- 27036529
TI  - Impact of glomerular filtration rate in colchicine toxicity.

PMID- 27036530
TI  - Models for integrating medical acupuncture into practice: an exploratory
      qualitative study of physicians' experiences.
AB  - BACKGROUND: Internationally, physicians are integrating medical acupuncture into
      their practice. Although there are some informative surveys and reviews, there
      are few international, exploratory studies detailing how physicians have
      accommodated medical acupuncture (eg, by modifying schedules, space and
      processes). OBJECTIVE: To examine how physicians integrate medical acupuncture
      into their practice. METHODS: Semi-structured interviews and participant
      observations of physicians practising medical acupuncture were conducted using
      convenience and snowball sampling. Data were analysed in NVivo and themes were
      developed. Despite variation, three principal models were developed to summarise
      the different ways that physicians integrated medical acupuncture into their
      practice, using the core concept of 'helping'. Quotes were used to illustrate
      each model and its corresponding themes. RESULTS: There were 25 participants from
      11 countries: 21 agreed to be interviewed and four engaged in participant
      observations. Seventy-two per cent were general practitioners. The three models
      were: (1) appointments (44%); (2) clinics (44%); and (3) full-time practice
      (24%). Some physicians held both appointments and regular clinics (models 1 and
      2). Most full-time physicians initially tried appointments and/or clinics. Some
      physicians charged to offset administration costs or compensate for their time.
      DISCUSSION: Despite variation within each category, the three models encapsulated
      how physicians described their integration of medical acupuncture. Physicians
      varied in how often they administered medical acupuncture and the amount of time
      they spent with patients. Although 24% of physicians surveyed administered
      medical acupuncture full-time, most practised it part-time. Each individual
      physician incorporated medical acupuncture in the way that worked best for their
      practice.

PMID- 27036531
TI  - ASSESSMENT OF INHALATION DOSE FROM THE INDOOR 222Rn AND 220Rn USING RAD7 AND
      PINHOLE CUP DOSEMETERS.
AB  - Radon is the most important source of natural radiation and is responsible for
      approximately half of the received dose from all sources. Most of this dose is
      from inhalation of the radon progeny, especially in closed atmospheres.
      Concentration of radon (222Rn) and thoron (220Rn) in the different villages of
      Jalandhar and Kapurthala district of Punjab has been calculated by pinhole cup
      dosemeters and RAD7. On an average, it has been observed from the study that the
      values of all the parameters calculated are higher in case of active monitoring
      than the passive monitoring. The calculated equilibrium equivalent 222Rn
      concentration (EECRn) and equilibrium equivalent 220Rn concentration (EECTh)
      fluctuate in the range from 5.58 to 34.29 and from 0.35 to 2.7 Bq m-3 as
      estimated by active technique, respectively. Similarly, the observed mean value
      of the potential alpha energy concentration of 222Rn (PAECRn) and 220Rn (PAECTh)
      is 4.55 and 4.34 mWL, respectively. The dose rate to the soft tissues and lung
      from indoor 222Rn varies from 0.06 to 0.38 and from 0.50 to 3.05 nGy h-1,
      respectively. The total annual effective dose for the residents of the study area
      is less than 10 mSv.

PMID- 27036532
TI  - STUDY OF RADIATION EXPOSURE DUE TO RADON, THORON AND THEIR PROGENY IN THE INDOOR
      ENVIRONMENT OF RAJPUR REGION OF UTTARAKHAND HIMALAYA.
AB  - In the present study, the measurements of indoor radon, thoron and their progeny
      concentrations have been carried out in the Rajpur region of Uttarakhand,
      Himalaya, India by using LR-115 solid-state nuclear track detector-based time
      integrated techniques. The gas concentrations have been measured by single-entry
      pin-hole dosemeter technique, while for the progeny concentrations, deposition
      based Direct Thoron and Radon Progeny Sensor technique has been used. The
      radiation doses due to the inhalation of radon, thoron and progeny have also been
      determined by using obtained concentrations of radon, thoron and their progeny in
      the study area. The average radon concentration varies from 75 to 123 Bq m-3 with
      an overall average of 89 Bq m-3 The average thoron concentration varies from 29
      to 55 Bq m-3 with an overall average of 38 Bq m-3 The total annual effective dose
      received due to radon, thoron and their progeny varies from 2.4 to 4.1 mSv y-1
      with an average of 2.9 mSv y-1 While the average equilibrium factor for radon and
      its progeny was found to be 0.39, for thoron and its progeny, it was 0.06.

PMID- 27036533
TI  - MEASUREMENT OF RADON, THORON AND THEIR PROGENY IN DIFFERENT TYPES OF DWELLING IN
      ALMORA DISTRICT OF KUMAUN HIMALAYAN REGION.
AB  - The indoor concentrations of radon (222Rn), thoron (220Rn) and their daughter
      products were measured in the dwellings of Almora district in Kumaun Himalaya,
      India using pin-hole dosemeters and deposition progeny sensors. The measurements
      were made in the residential houses built of mud, stone with cement plaster and
      cemented house during winter season. Average [geometric mean (GM) values] radon
      and thoron concentrations for all dwellings were found to be 99.82 and 79.70 Bq m
      3, respectively, while average equilibrium equivalent radon concentration and
      equilibrium equivalent thoron concentration (measured for the first time for this
      region) were measured at 35.22 and 2.52 Bq m-3, respectively. Radon concentration
      (GM values) was found to be 110.73, 97.00 and 93.85 Bq m-3 for mud houses, stone
      with cemented plaster houses and cemented houses, respectively. On the other
      hand, thoron concentration values were 87.10, 75.79 and 75.68 Bq m-3 for cemented
      houses, mud houses and stone with cemented plaster houses, respectively.
      Interpretations have been made on the basis of measured radon/thoron and progeny
      concentration values with respect to the difference of construction material of
      the dwellings.

PMID- 27036534
TI  - NATURAL RADIONUCLIDE LEVELS IN SEDIMENTS OF CAUVERY RIVERINE ENVIRONMENT.
AB  - The paper presents the systematic measurement of activity concentrations of 40K,
      226Ra and 232Th in sediment sample of Cauvery river of Karnataka, South India.
      Activity was measured using HpGe gamma ray spectrometer, and the mean values of
      40K, 226Ra and 232Th in the sediment samples were found to be 144.31, 32.05 and
      61.70 Bq kg-1, respectively. To assess the radiological hazards in the samples,
      radium equivalent (Raeq), absorbed dose (D), annual effective equivalent dose
      (AEED), activity utilisation index (AUI) and annual gonadal dose equivalent
      (AGDE) values associated with the radionuclides were calculated and compared with
      international recommended values.

PMID- 27036535
TI  - Effects of phosphodiester and phosphorothioate ODN2216 on leukotriene synthesis
      in human neutrophils and neutrophil apoptosis.
AB  - Polymorphonuclear leukocytes (PMNLs, neutrophils) play a major role in the
      initiation and resolution of the inflammatory response, and neutrophil apoptosis
      is a critical step in resolving inflammation. We examined the effects of
      oligodeoxynucleotide (ODN) species with different numbers of phosphodiester and
      phosphorothioate bonds on leukotriene synthesis in PMNLs and on neutrophil
      apoptosis. Our modifications were based on the well-known ODN2216 molecule (Krug
      et al., 2001). Treatment of cultured human neutrophils with ODN2216 accelerated
      apoptosis except in the case of a species with only phosphodiester bonds. The
      ODNs with poly(g) (phosphorothioate) sequences at both ends and a phosphodiester
      inner core had maximal effects on leukotriene synthesis in neutrophils and
      inhibited formation of 5-lipoxygenase metabolites. Addition of phosphodiester and
      phosphorothioate ODNs to PMNLs produced distinct effects on superoxide and nitric
      oxide formation: phosphorothioate-containing ODNs concomitantly stimulated
      production of nitric oxide and superoxide, which may rapidly combine to generate
      peroxynitrite. Altogether, our results describe strong activation of neutrophil's
      cellular responses by phosphorothioate ODN2216. We propose that phosphorothioate
      modification of ODNs represents a potential mechanism of PMNL activation. 

PMID- 27036536
TI  - Erratum.

PMID- 27036537
TI  - Erratum.

PMID- 27036538
TI  - How older adults with mild cognitive impairment relate to technology as part of
      present and future everyday life: a qualitative study.
AB  - BACKGROUND: Existing everyday technology as well as potential future technology
      may offer both challenges and possibilities in the everyday occupations of
      persons with cognitive decline. To meet their wishes and needs, the perspective
      of the persons themselves is an important starting point in intervention planning
      involving technology. The aim of this study was to explore how persons with mild
      cognitive impairment relate to technology as a part of and as potential support
      in everyday life - both present and future. METHODS: Qualitative in-depth
      interviews with six participants aged 61-86 were conducted and analyzed, using a
      grounded theory approach. RESULTS: The findings describe the participants'
      different ways of relating to existing and potential future technology in
      everyday occupations as a continuum of downsizing, retaining, and updating.
      Multiple conditions in different combinations affected both their actions taken
      and assumptions made towards technology in this continuum. Both when downsizing
      doing and technology use to achieve simplicity in everyday life and when striving
      for or struggling with updating, trade-offs between desired and adverse outcomes
      were made, challenging take-off runs were endured, and negotiations of the price
      worth paying took place. CONCLUSIONS: Our findings suggest that persons with mild
      cognitive impairment may relate to technology in various ways to meet needs of
      downsized doing, but are reluctant to adopt video-based monitoring technology
      intended to support valued occupations. Feasibility testing of using already
      incorporated everyday technologies such as smartphones and tablets as platforms
      for future technology support in everyday occupations is suggested.

PMID- 27036539
TI  - [Innovative anticancer agents reserved to hospital use and not involved in the
      hospital budget: Creation and evolution].

PMID- 27036540
TI  - Totally laparoscopic versus laparoscopic-assisted total gastrectomy for upper and
      middle gastric cancer: a single-unit experience of 253 cases with meta-analysis.
AB  - BACKGROUND: Laparoscopic-assisted total gastrectomy (LATG) is the most commonly
      used methods of laparoscopic gastrectomy for upper and middle gastric cancer.
      However, totally laparoscopic total gastrectomy (TLTG) is unpopular because
      reconstruction is difficult, especially for the intracorporeal
      esophagojejunostomy. We adopted TLTG with various types of intracorporeal
      esophagojejunostomy. In this study, we compared LATG and TLTG to evaluate their
      outcomes. METHODS: From March 2006 to September 2015, 253 patients with upper and
      middle gastric cancer underwent laparoscopic total gastrectomy (LTG), 145
      patients underwent LATG, and 108 patients underwent TLTG. The clinicopathological
      characteristics and postoperative outcomes were retrospectively compared between
      the two groups. Furthermore, a systematic review and meta-analysis were
      conducted. RESULTS: The operation time and estimated blood loss were similar
      between the groups. There were no significant differences in first flatus, diet
      initiation, and postoperative hospital stay. The surgical complication rates were
      17.2% (25/145) and 13.9% (15/108) in the LATG and TLTG groups, respectively. The
      meta-analysis also revealed no significant differences in the operation time,
      estimated blood loss, time to first flatus, length of hospital stay, overall, and
      anastomosis-related complications among the groups. CONCLUSIONS: TLTG is a
      feasible choice for gastric cancer patients, with comparable results to the LATG
      approach.

PMID- 27036545
TI  - Association of maternal diabetes/glycosuria and pre-pregnancy body mass index
      with offspring indicators of non-alcoholic fatty liver disease.
AB  - BACKGROUND: Little is known about early life determinants of non-alcoholic fatty
      liver disease (NAFLD). We examined associations of maternal pregnancy
      diabetes/glycosuria and pre-pregnancy body mass index (BMI) with offspring
      markers of NAFLD and liver pathology and examined mediation by birthweight and
      concurrent offspring adiposity. METHODS: We used data from a UK prospective
      pregnancy cohort. Offspring underwent abdominal ultrasonography (USS) at mean age
      17.8 years. Outcomes included USS-assessed fatty liver, estimated liver volume
      and shear velocity, a variant of elastography (a marker of liver fibrosis) (N = 1
      215) and blood-based markers of liver pathology [alanine amino transferase,
      aspartate amino transferase, gamma- glutamyltransferase and haptoglobin] (N = 2
      359). RESULTS: 2.1 % (N = 25) of participants had USS-assessed fatty liver
      [maternal diabetes/glycosuria (N = 7) and no diabetes/glycosuria (N = 18)].
      Maternal diabetes/glycosuria was associated with greater odds of offspring USS
      fatty liver in confounder adjusted models [adjusted odds ratio (aOR) 6.74 (95 %
      confidence interval (CI) 2.47, 18.40)] and higher shear velocity [adjusted ratio
      of geometric mean (aRGM):1.10 (95 % CI 1.05, 1.15)]. These associations were not
      mediated by offspring birthweight or concurrent adiposity. Maternal
      diabetes/glycosuria was not associated with liver volume or blood-based outcomes.
      Greater maternal pre-pregnancy BMI was associated with greater odds of offspring
      USS fatty liver [aOR 2.72 (95 % CI: 1.20, 6.15)], higher liver volume [aRGM 1.03
      (95 % CI 1.00, 1.07)] and shear velocity [aRGM1.03 (95 % CI: 1.01, 1.06)] in
      confounder adjusted models. These associations were largely mediated by offspring
      adiposity. Maternal pre-pregnancy BMI was not consistently associated with blood
      based outcomes. CONCLUSIONS: Results suggest that maternal pregnancy
      diabetes/glycosuria is associated with offspring NAFLD through mechanisms other
      than offspring's own adiposity.

PMID- 27036547
TI  - Changing definitions altered multimorbidity prevalence, but not burden
      associations, in a musculoskeletal population.
AB  - OBJECTIVES: The inclusion of musculoskeletal conditions within multimorbidity
      research is inconsistent, and working-age populations are largely ignored. We
      aimed to: (1) estimate multimorbidity prevalence among working-age individuals
      with a range of musculoskeletal conditions; and (2) better understand the
      implications of decisions about the number and range of conditions constituting
      multimorbidity on the strength of associations between multimorbidity and burden
      (e.g., health status and health care utilization). STUDY DESIGN AND SETTING:
      Using data from the Australian National Health Survey 2007-08, the associations
      between burden measures and three ways of operationalizing multimorbidity
      (survey, policy, and research based) within the working-age (18-64 years)
      musculoskeletal population were estimated using multiple logistic regression (age
      and gender adjusted). RESULTS: Depending on definition, from 20.2% to 75.4% of
      working-age individuals with musculoskeletal conditions have multimorbidity.
      Irrespective of definition, multimorbidity was associated with increased
      likelihood of subjective health burden, pain or musculoskeletal medicines use,
      nonmusculoskeletal specialist and pharmacist (advice only) consultations, and
      reduced likelihood of not consulting health professionals. A group with
      intermediate health outcomes was considered multimorbid by some, but not all
      definitions. With the restrictive policy and research multimorbidity definitions,
      this intermediate group is included within the reference population (i.e., are
      considered nonmultimorbid). This worsens the reference group's apparent health
      status thereby leveling the comparative burden between those with and without
      multimorbidity. Consequently, dichotomous cut points lead to similar associations
      with burden measures despite the increasingly restrictive multimorbidity
      definitions used. CONCLUSIONS: All multimorbidity definitions were associated
      with burden among the working-age musculoskeletal population. However,
      dichotomous cut points obscure the gradient of increased burden associated with
      restrictive definitions.

PMID- 27036546
TI  - X-linked intellectual disability gene CASK regulates postnatal brain growth in a
      non-cell autonomous manner.
AB  - The phenotypic spectrum among girls with heterozygous mutations in the X-linked
      intellectual disability (XLID) gene CASK (calcium/calmodulin-dependent serine
      protein kinase) includes postnatal microcephaly, ponto-cerebellar hypoplasia,
      seizures, optic nerve hypoplasia, growth retardation and hypotonia. Although CASK
      knockout mice were previously reported to exhibit perinatal lethality and a 3
      fold increased apoptotic rate in the brain, CASK deletion was not found to affect
      neuronal physiology and their electrical properties. The pathogenesis of CASK
      associated disorders and the potential function of CASK therefore remains
      unknown. Here, using Cre-LoxP mediated gene excision experiments; we demonstrate
      that deleting CASK specifically from mouse cerebellar neurons does not alter the
      cerebellar architecture or function. We demonstrate that the neuron-specific
      deletion of CASK in mice does not cause perinatal lethality but induces severe
      recurrent epileptic seizures and growth retardation before the onset of
      adulthood. Furthermore, we demonstrate that although neuron-specific
      haploinsufficiency of CASK is inconsequential, the CASK mutation associated human
      phenotypes are replicated with high fidelity in CASK heterozygous knockout female
      mice (CASK ((+/-))). These data suggest that CASK-related phenotypes are not
      purely neuronal in origin. Surprisingly, the observed microcephaly in CASK ((+/
      )) animals is not associated with a specific loss of CASK null brain cells
      indicating that CASK regulates postnatal brain growth in a non-cell autonomous
      manner. Using biochemical assay, we also demonstrate that CASK can interact with
      metabolic proteins. CASK knockdown in human cell lines cause reduced cellular
      respiration and CASK ((+/-)) mice display abnormalities in muscle and brain
      oxidative metabolism, suggesting a novel function of CASK in metabolism. Our data
      implies that some phenotypic components of CASK heterozygous deletion mutation
      associated disorders represent systemic manifestation of metabolic stress and
      therefore amenable to therapeutic intervention. 

PMID- 27036548
TI  - Prevalence of RhD status and clinical application of non-invasive prenatal
      determination of fetal RHD in maternal plasma: a 5 year experience in Cyprus.
AB  - BACKGROUND: After the discovery that cell-free fetal DNA (cffDNA) is circulating
      in the maternal plasma of pregnant women, non-invasive prenatal diagnosis for
      fetal RhD in maternal plasma in RhD negative women at risk for haemolytic disease
      of the newborn (HDN) was clinically established and used by many laboratories.
      The objectives of this study are: (a) to assess the feasibility and report our
      experiences of the routine implementation of fetal RHD genotyping by analysis of
      cffDNA extracted from maternal plasma of RhD negative women at risk of HDN, and
      (b) to estimate the RhD phenotype frequencies, the RHD genotype frequencies and
      the RhD zygosity in the Cypriot population. METHODS: cffDNA was extracted from
      maternal plasma of 73 RhD negative pregnant women. Real-Time Multiplex-PCR was
      used to amplify regions of RHD gene in exons 4, 5 and 10. RhD phenotypes were
      determined on 445 random samples using conventional agglutination slide test.
      RESULTS: The fetus was predicted to be positive in 53 cases and negative in 18
      cases. Two of cases were identified as D-variants, weak D type-1 and 11. The
      frequency of RhD negative homozygosity in the Cypriot population was estimated to
      be 7.2%, while the frequencies of RHD hemizygosity and RhD positive homozygosity
      was calculated to be 39.2 and 53.6%, respectively. CONCLUSION: Fetal RHD
      genotyping can be accurately determined using cffDNA from maternal plasma. The
      implementation of the test has eliminated all use of unnecessary anti-D and
      reduced the total use of anti-D by 25.3% while achieving appropriate management
      of the RhD negative pregnancies.

PMID- 27036549
TI  - Targeted drugs and Psycho-oncological intervention for breast cancer patients.
AB  - Personalized medicine is a new field based on molecular biology and genomics in
      which targeted tumor therapies are administered to patients. Psycho-oncology is a
      complementary approach that considers social and psychological aspects of
      patients as part of the treatments for cancer patients. The aim of this mini
      review is to weigh clinical benefits for breast cancer patients of both
      treatments and possibly enhance benefits by modulating the use of both
      interventions. We have compared and evaluated on the one hand the use of anti
      Vascular Endothelial Growth Factor and, on the other hand, psycho-oncological
      interventions in metastatic and non-metastatic breast cancer patients.Both
      treatments did not increase survival of metastatic breast cancer patients, while
      in a selected study psycho-oncological interventions extended lifespan of non
      metastatic breast cancer patients and ameliorate psychological and social factors
      of metastatic breast cancer patients. Because the two approaches address
      completely different aspects of cancer patients, if the comparison is limited to
      the extension of survival, the value of these two treatments cannot be assessed
      and compared.It is likely that by comparing patients reported outcomes, possibly
      by using standardized Quality of Life questionnaires, both patients and health
      care providers can weigh the benefits of the two treatments. It is therefore
      important to evaluate the use of cancer patients' quality of life measures as a
      mean to improve their experiences about life and treatment, and possibly to
      extend their survival.

PMID- 27036550
TI  - All-trans retinoic acids induce differentiation and sensitize a radioresistant
      breast cancer cells to chemotherapy.
AB  - BACKGROUND: Radiotherapy is of critical importance in the treatment of breast
      cancer. However, not all patients derive therapeutic benefit and some breast
      cancers are resistant to the treatment, and are thus evidenced with prospective
      distant metastatic spread and local recurrence. In this study, we investigated
      the potential therapeutic effects of all-trans retinoic acid (ATRA) on radiation
      resistant breast cancer cells and the associated invasiveness. METHODS: The
      MCF7/C6 cells with gained radiation resistance after a long term treatment with
      fractionated ionizing radiation were derived from human breast cancer MCF7 cell
      line, and are enriched with cells expressing putative breast cancer stem cell
      biomarker CD44(+)/CD24(-/low)/ALDH(+). The enhanced invasiveness and the acquired
      resistances to chemotherapeutic treatments of MCF7/C6 cells were measured, and
      potential effects of all-trans retinoic acid (ATRA) on the induction of
      differentiation, invasion and migration, and on the sensitivities to
      chemotherapies in MCF7/C6 cells were investigated. RESULTS: MCF7/C6 cells are
      with enrichment of cancer stem-cell like cells with positive staining of
      CD44(+)/CD24(-/low), OCT3/4 and NANOG. MCF7/C6 cells showed an increased
      tumoregensis potential and enhanced aggressiveness of invasion and migration.
      Treatment with ATRA induces the differentiation in MCF7/C6 cells, resulting in
      reduced invasiveness and migration, and increased sensitivity to Epirubincin
      treatment. CONCLUSION: Our study suggests a potential clinic impact for ATRA as a
      chemotherapeutic agent for treatment of therapy-resistant breast cancer
      especially for the metastatic lesions. The study also provides a rationale for
      ATRA as a sensitizer of Epirubincin, a first-line treatment option for breast
      cancer patients.

PMID- 27036551
TI  - Relationships Among Substance Use, Multiple Sexual Partners, and Condomless Sex.
AB  - Male and female students manifest different behaviors in condomless sex. This
      cross-sectional, exploratory, correlational study examined the differences in
      risk factors for condomless sex between male and female high school students,
      using secondary data from 4,968 sexually active males and females participating
      in the 2011 National Youth Risk Behavior Survey. Results in descriptive
      statistics and multivariate binary logistic regressions revealed that condomless
      sex was reported as 39.70% in general. A greater proportion of females engaged in
      condomless sex (23.26%) than did males (16.44%). Physical abuse by sex partners
      was a common reason for failure to use condoms regardless of gender. Lower condom
      use was found in (1) those experiencing forced sex by a partner in males, (2)
      female smokers, and (3) female with multiple sex partners. Thus, sexual health
      education should address the different risk factors and consider gender
      characteristics to reduce condomless sex.

PMID- 27036552
TI  - Hmga2 is necessary for Otx2-dependent exit of embryonic stem cells from the
      pluripotent ground state.
AB  - BACKGROUND: A crucial event in the differentiation of mouse embryonic stem cells
      (ESCs) is the exit from the pluripotent ground state that leads to the
      acquisition of the 'primed' pluripotent phenotype, characteristic of the epiblast
      like stem cells (EpiLCs). The transcription factors Oct4 and Otx2 play a key role
      in this phenomenon. In particular, Otx2 pioneers and activates new enhancers,
      which are silent in ESCs and which control the transcription of genes responsible
      for the acquisition of the EpiLC phenotype. An important point that remains to be
      addressed is the mechanism through which Otx2 engages the new enhancers and
      stably associates with them. Hmga2 is a member of the high-mobility group family
      of proteins, non-histone components of chromatin whose expression is high during
      embryogenesis and becomes low or undetectable in adults. Its high expression
      during embryogenesis suggests that Hmga2 fulfills important roles in development.
      RESULTS: Here, we demonstrate that Hmga2 accumulates soon after the induction of
      ESC differentiation. Its suppression hampers the exit of ESCs from the
      pluripotent ground state and their differentiation into EpiLCs. Mechanistically,
      Hmga2 controls the differentiation process by cooperating with Otx2 in the
      pioneering of new enhancers. In Hmga2 null induced pluripotent stem cells we
      observe that Otx2 fails to regulate its target genes upon the induction of
      differentiation. Hmga2 associates to Otx2-bound loci in EpiLCs, and in Hmga2 KO
      cells Otx2 is unable to engage and activate the new enhancers, thus indicating
      that Hmga2 is required for the binding of Otx2 to its cis-elements. We find that
      this mechanism also operates on the Hmga2 gene, which is one of the targets of
      Otx2, thus indicating the existence of a positive feedback loop. CONCLUSIONS: Our
      findings reveal a novel mechanism necessary for the exit of ESCs from the
      pluripotent ground state. Upon the induction of ESC differentiation, Otx2 alone
      or in combination with Oct4 engages new enhancers, which are silent in
      undifferentiated ESCs. The Hmga2 gene is activated by Otx2 and Hmga2 protein
      binds to the enhancers targeted by Otx2, thus facilitating the engagement and/or
      the stable association of Otx2. Therefore, our results demonstrate that Hmga2 is
      a key element of the regulatory network that governs the exit of ESCs from the
      pluripotent ground state.

PMID- 27036553
TI  - Protective hybrid coating containing silver, copper and zinc cations effective
      against human immunodeficiency virus and other enveloped viruses.
AB  - BACKGROUND: Healthcare-acquired infections by pathogenic microorganisms including
      viruses represent significant health concern worldwide. Next to direct
      transmission from person-to-person also indirect transmission from contaminated
      surfaces is well documented and important route of infections. Here, we tested
      antiviral properties of hybrid coating containing silver, copper and zinc cations
      that was previously shown to be effective against pathogenic bacteria including
      methicillin-resistant Staphylococcus aureus. Hybrid coatings containing silver,
      copper and zinc cations were prepared through radical polymerization via sol-gel
      method and applied on glass slides or into the wells of polymethylmethacrylate
      plates. A 10 MUl droplet of several viruses such as human immunodeficiency virus
      type 1 (HIV-1), influenza, dengue virus, herpes simplex virus, and coxsackievirus
      was added to coated and uncoated slides or plates, incubated usually from 5 to
      240 min and followed by titer determination of recovered virus. RESULTS: Scanning
      electron microscopy analysis showed better adhesion of coatings on glass
      surfaces, which resulted in 99.5-100 % HIV-1 titer reduction (3.1 +/- 0.8
      log10TCID50, n = 3) already after 20 min of exposure to coatings, than on coated
      polymethylmethacrylate plates with 75-100 % (1.7 +/- 1.1 log10TCID50, n = 3) and
      98-100 % (2.3 +/- 0.5 log10TCID50, n = 3) HIV-1 titer reduction after 20 and 120
      min of exposure, respectively. Slower virucidal kinetics was observed with other
      enveloped viruses, where 240 min exposure to coated slides lead to 97 % (dengue),
      100 % (herpes simplex) and 77 % (influenza) reduction in virus titers.
      Interestingly, only marginal reduction in viral titer after 240 min of exposure
      was noticed for non-enveloped coxsackie B3 virus. CONCLUSIONS: Our hybrid
      coatings showed virucidal activity against HIV and other enveloped viruses thus
      providing further findings towards development of broad-spectrum antimicrobial
      coating suitable for surfaces in healthcare settings.

PMID- 27036554
TI  - Determinants of delay in malaria care-seeking behaviour for children 15 years and
      under in Bata district, Equatorial Guinea.
AB  - BACKGROUND: Malaria remains a major cause of morbidity and mortality in children
      under 5 years of age in Equatorial Guinea. Early appropriate treatment can reduce
      progression of the illness to severe stages, thus reducing of mortality,
      morbidity and onward transmission. The factors that contribute to malaria
      treatment delay have not been studied previously in Equatorial Guinea. The
      objective of this study was to assess the determinants of delay in seeking
      malaria treatment for children in the Bata district, in mainland Equatorial
      Guinea. METHODOLOGY: A cross-sectional study was conducted in Bata district, in
      2013, which involved 428 houses in 18 rural villages and 26 urban neighbourhoods.
      Household caregivers were identified in each house and asked about their
      knowledge of malaria and about the management of the last reported malaria
      episode in a child 15 years and younger under their care. Bivariate and
      multivariate statistical analyses were conducted to determine the relevance of
      socio-economic, geographical and behavioural factors on delays in care-seeking
      behaviour. RESULTS: Nearly half of the children sought treatment at least 24 h
      after the onset of the symptoms. The median delay in seeking care was 2.8 days.
      Children from households with the highest socio-economic status were less likely
      to be delayed in seeking care than those from households with the lowest socio
      economic status (OR 0.37, 95% CI 0.19-0.72). Children that first received
      treatment at home, mainly paracetamol, were more than twice more likely to be
      delayed for seeking care, than children who did not first receive treatment at
      home (OR 2.36, 95% CI 1.45-3.83). Children living in a distance >3 km from the
      nearest health facility were almost two times more likely to be delayed in
      seeking care than those living closer to a facility but with non significant
      association once adjusted for other variables (OR 1.75, 95% CI 0.88-3.47).
      CONCLUSION: To decrease malaria morbidity and mortality in Bata district, efforts
      should be addressed to reduce household delays in seeking care. It is necessary
      to provide free access to effective malaria diagnosis and treatment, to reinforce
      malaria management at community level through community health workers and drug
      sellers and to increase awareness on the severity of malaria, the importance of
      early diagnosis and appropriate treatment.

PMID- 27036556
TI  - Erratum to: BayesFlow: latent modeling of flow cytometry cell populations.

PMID- 27036555
TI  - TOPPITS: Trial Of Proton Pump Inhibitors in Throat Symptoms. Study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Persistent throat symptoms and Extra Oesophageal Reflux (EOR) are
      among the commonest reasons for attendance at a secondary care throat or voice
      clinic. There is a growing trend to treat throat symptom patients with proton
      pump inhibitors (PPIs) to suppress stomach acid, but most controlled studies fail
      to demonstrate a significant benefit of PPI over placebo. In addition, patient
      views on PPI use vary widely. METHODS/DESIGN: A UK multi-centre, randomised,
      controlled trial for adults with persistent throat symptoms to compare the
      effectiveness of treatment with the proton pump inhibitor (PPI) lansoprazole
      versus placebo. The trial includes a six-month internal pilot, during which three
      sites will recruit 30 participants in total, to assess the practicality of the
      trial and assess the study procedures and willingness of the patient population
      to participate. If the pilot is successful, three additional sites will be opened
      to recruitment, and a further 302 participants recruited across the six main
      trial sites. Further trial sites may be opened, as necessary. The main trial will
      continue for a further 18 months. Participants will be followed up for 12 months
      from randomisation, throughout which both primary and secondary outcome data will
      be collected. The primary outcome is change in Reflux Symptom Index (RSI) score,
      the 'area standard' for this type of assessment, after 16 weeks (four months) of
      treatment. Secondary outcomes are RSI changes at 12 months after randomisation,
      Quality of Life assessment at four and 12 months, laryngeal mucosal changes,
      assessments of compliance and side effects, and patient-reported satisfaction.
      DISCUSSION: TOPPITS is designed to evaluate the relative effectiveness of
      treatment with a proton pump inhibitor versus placebo in patients with persistent
      throat symptoms. This will provide valuable information to clinicians and GPs
      regarding the treatment and management of care for these patients, on changes in
      symptoms, and in Quality of Life, over time. TRIAL REGISTRATION: ISRCTN38578686 .
      Registered 17 April 2014.

PMID- 27036557
TI  - Future qualification as a qualified clinical medical physicist should be
      restricted to doctoral degree holders.

PMID- 27036558
TI  - Assessment of metal artifact reduction methods in pelvic CT.
AB  - PURPOSE: Metal artifact reduction (MAR) produces images with improved quality
      potentially leading to confident and reliable clinical diagnosis and therapy
      planning. In this work, the authors evaluate the performance of five MAR
      techniques for the assessment of computed tomography images of patients with hip
      prostheses. METHODS: Five MAR algorithms were evaluated using simulation and
      clinical studies. The algorithms included one-dimensional linear interpolation
      (LI) of the corrupted projection bins in the sinogram, two-dimensional
      interpolation (2D), a normalized metal artifact reduction (NMAR) technique, a
      metal deletion technique, and a maximum a posteriori completion (MAPC) approach.
      The algorithms were applied to ten simulated datasets as well as 30 clinical
      studies of patients with metallic hip implants. Qualitative evaluations were
      performed by two blinded experienced radiologists who ranked overall artifact
      severity and pelvic organ recognition for each algorithm by assigning scores from
      zero to five (zero indicating totally obscured organs with no structures
      identifiable and five indicating recognition with high confidence). RESULTS:
      Simulation studies revealed that 2D, NMAR, and MAPC techniques performed almost
      equally well in all regions. LI falls behind the other approaches in terms of
      reducing dark streaking artifacts as well as preserving unaffected regions (p <
      0.05). Visual assessment of clinical datasets revealed the superiority of NMAR
      and MAPC in the evaluated pelvic organs and in terms of overall image quality.
      CONCLUSIONS: Overall, all methods, except LI, performed equally well in artifact
      free regions. Considering both clinical and simulation studies, 2D, NMAR, and
      MAPC seem to outperform the other techniques.

PMID- 27036559
TI  - A novel property of gold nanoparticles: Free radical generation under microwave
      irradiation.
AB  - PURPOSE: Gold nanoparticles (GNPs) are known to be effective mediators in
      microwave hyperthermia. Interaction with an electromagnetic field, large surface
      to volume ratio, and size quantization of nanoparticles (NPs) can lead to
      increased cell killing beyond pure heating effects. The purpose of this study is
      to explore the possibility of free radical generation by GNPs in aqueous media
      when they are exposed to a microwave field. METHODS: A number of samples with 500
      mM 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in 20 ppm GNP colloidal suspensions
      were scanned with an electron paramagnetic resonance (EPR)/electron spin
      resonance spectrometer to generate and detect free radicals. A fixed (9.68 GHz)
      frequency microwave from the spectrometer has served for both generation and
      detection of radicals. EPR spectra obtained as first derivatives of intensity
      with the spectrometer were double integrated to get the free radical signal
      intensities. Power dependence of radical intensity was studied by applying
      various levels of microwave power (12.5, 49.7, and 125 mW) while keeping all
      other scan parameters the same. Free radical signal intensities from initial and
      final scans, acquired at the same power levels, were compared. RESULTS: Hydroxyl
      radical (OH?) signal was found to be generated due to the exposure of GNP-DMPO
      colloidal samples to a microwave field. Intensity of OH? signal thus generated at
      12.5 mW microwave power for 2.8 min was close to the intensity of OH? signal
      obtained from a water-DMPO sample exposed to 1.5 Gy ionizing radiation dose. For
      repeated scans, higher OH? intensities were observed in the final scan for higher
      power levels applied between the initial and the final scans. Final intensities
      were higher also for a shorter time interval between the initial and the final
      scans. CONCLUSIONS: Our results observed for the first time demonstrate that GNPs
      generate OH? radicals in aqueous media when they are exposed to a microwave
      field. If OH? radicals can be generated close to deoxyribonucleic acid of cells
      by proper localization of NPs, NP-aided microwave hyperthermia can yield cell
      killing via both elevated temperature and free radical generation.

PMID- 27036560
TI  - Ultrasound viscoelasticity assessment using an adaptive torsional shear wave
      propagation method.
AB  - PURPOSE: Different approaches have been used in dynamic elastography to assess
      mechanical properties of biological tissues. Most techniques are based on a
      simple inversion based on the measurement of the shear wave speed to assess
      elasticity, whereas some recent strategies use more elaborated analytical or
      finite element method (FEM) models. In this study, a new method is proposed for
      the quantification of both shear storage and loss moduli of confined lesions, in
      the context of breast imaging, using adaptive torsional shear waves (ATSWs)
      generated remotely with radiation pressure. METHODS: A FEM model was developed to
      solve the inverse wave propagation problem and obtain viscoelastic properties of
      interrogated media. The inverse problem was formulated and solved in the
      frequency domain and its robustness to noise and geometric constraints was
      evaluated. The proposed model was validated in vitro with two independent
      rheology methods on several homogeneous and heterogeneous breast tissue-mimicking
      phantoms over a broad range of frequencies (up to 400 Hz). RESULTS: Viscoelastic
      properties matched benchmark rheology methods with discrepancies of 8%-38% for
      the shear modulus G' and 9%-67% for the loss modulus G". The robustness study
      indicated good estimations of storage and loss moduli (maximum mean errors of 19%
      on G' and 32% on G") for signal-to-noise ratios between 19.5 and 8.5 dB. Larger
      errors were noticed in the case of biases in lesion dimension and position.
      CONCLUSIONS: The ATSW method revealed that it is possible to estimate the
      viscoelasticity of biological tissues with torsional shear waves when small
      biases in lesion geometry exist.

PMID- 27036561
TI  - Comparison of three dimensional strain volume reconstructions using SOUPR and
      wobbler based acquisitions: A phantom study.
AB  - PURPOSE: Ultrasound strain imaging is a relatively low cost and portable modality
      for monitoring percutaneous thermal ablation of liver neoplasms. However, a 3D
      strain volume reconstruction from existing 2D strain images is necessary to fully
      delineate the thermal dose distribution. Tissue mimicking (TM) phantom
      experiments were performed to validate a novel volume reconstruction algorithm
      referred to as sheaf of ultrasound planes reconstruction (SOUPR), based on a
      series of 2D rotational imaging planes. METHODS: Reconstruction using SOUPR was
      formulated as an optimization problem with constraints on data consistency with
      2D strain images and data smoothness of the volume data. Reconstructed ablation
      inclusion dimensions, volume, and elastographic signal to noise ratio (SNRe) and
      contrast to noise ratio (CNRe) were compared with conventional 3D ultrasound
      strain imaging based on interpolating a series of quasiparallel 2D strain images
      with a wobbler transducer. RESULTS: Volume estimates of the phantom inclusion
      were in a similar range for both acquisition approaches. SNRe and CNRe obtained
      with SOUPR were significantly higher on the order of 250% and 166%, respectively.
      The mean error of the inclusion dimension reconstructed with a wobbler transducer
      was on the order of 10.4%, 3.5%, and 19.0% along the X, Y, and Z axes,
      respectively, while the error with SOUPR was on the order of 2.6%, 2.8%, and
      9.6%. A qualitative comparison of SOUPR and wobbler reconstruction was also
      performed using a thermally ablated region created in ex vivo bovine liver
      tissue. CONCLUSIONS: The authors have demonstrated using experimental evaluations
      with a TM phantom that the reconstruction results obtained with SOUPR were
      superior when compared with a conventional wobbler transducer in terms of
      inclusion shape preservation and detectability.

PMID- 27036562
TI  - A quantitative metrology for performance characterization of five breast
      tomosynthesis systems based on an anthropomorphic phantom.
AB  - PURPOSE: In medical imaging systems, proper rendition of anatomy is essential in
      discerning normal tissue from disease. Currently, digital breast tomosynthesis
      (DBT) systems are evaluated using subjective evaluation of lesion visibility in
      uniform phantoms. This study involved the development of a new methodology to
      objectively measure the rendition of a 3D breast model by an anthropomorphic
      breast phantom, and its implementation on five clinical DBT systems of different
      makes and models. METHODS: A 3D, patient-based breast phantom was fabricated
      based on XCAT breast models. This phantom was imaged on representative breast
      tomosynthesis systems. The ability of tomosynthesis systems to accurately
      reproduce the 3D structure of the breast was assessed by computational analysis
      of the resultant images in terms of three groups of indices: contrast index (CI),
      reflective of local difference between adipose and glandular material; adipose
      variability index (AVI), reflective of contributions of noise and artifacts
      within uniform adipose regions; and contrast detectability, which describes
      contrast against local background variability and is described by contrast
      variability index (CVI), coefficient of variation (COV), contrast to adipose
      variability index (CAVI), and contrast to noise ratio index (CNRI). The indices
      were obtained by comparing the image data to the gold standard 3D distribution of
      breast tissue in the model. Corresponding indices were measured within variable
      region of interest (ROI) sizes ranging from 10 to 37 mm. The characterization was
      performed on five tomosynthesis systems: Fuji Aspire Crystal, GE Essential,
      Hologic Dimension, IMS Giotto, and Siemens Inspiration, all evaluated at a fixed
      dose of 1.5 mGy average glandular dose, anonymized in random order from A to E.
      RESULTS: Results are provided as a function of ROI size. The systems ranked
      orders in terms of CI with values of 7.4%, 7.0%, 6.9%, 6.4%, and 5.2% for systems
      A-E, respectively. This system ranking was identical for CNRI. Both CI and CNRI
      were constant over ROI size. The ranking was similar for CVI. The COV also
      changed little with ROI size and was similar across systems. For 10 mm ROIs, the
      average system COV was 0.7, which reduced to 0.5 with 37 mm ROIs. Two systems (A
      and B) exhibited highest AVI values when measured in 10 mm ROIs. This, however,
      was ROI-size-dependent with the three other systems (C-E) yielding higher AVI
      values when measured with 37 mm ROIs. Two systems (B and E) showed inferior CAVI
      compared to others. CONCLUSIONS: The quality of rendition tracked with
      differences in image appearance across systems. The findings illustrate that the
      anthropomorphic phantom can be used as a basis to extract quantitative values of
      image attributes in DBT.

PMID- 27036563
TI  - Design and characterization of a new high-dose-rate brachytherapy Valencia
      applicator for larger skin lesions.
AB  - PURPOSE: The aims of this study were (i) to design a new high-dose-rate (HDR)
      brachytherapy applicator for treating surface lesions with planning target
      volumes larger than 3 cm in diameter and up to 5 cm in size, using the
      microSelectron-HDR or Flexitron afterloader (Elekta Brachytherapy) with a (192)Ir
      source; (ii) to calculate by means of the Monte Carlo (MC) method the dose
      distribution for the new applicator when it is placed against a water phantom;
      and (iii) to validate experimentally the dose distributions in water. METHODS:
      The penelope2008 MC code was used to optimize dwell positions and dwell times.
      Next, the dose distribution in a water phantom and the leakage dose distribution
      around the applicator were calculated. Finally, MC data were validated
      experimentally for a (192)Ir mHDR-v2 source by measuring (i) dose distributions
      with radiochromic EBT3 films (ISP); (ii) percentage depth-dose (PDD) curve with
      the parallel-plate ionization chamber Advanced Markus (PTW); and (iii) absolute
      dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber.
      RESULTS: The new applicator is made of tungsten alloy (Densimet) and consists of
      a set of interchangeable collimators. Three catheters are used to allocate the
      source at prefixed dwell positions with preset weights to produce a homogenous
      dose distribution at the typical prescription depth of 3 mm in water. The same
      plan is used for all available collimators. PDD, absolute dose rate per unit of
      air kerma strength, and off-axis profiles in a cylindrical water phantom are
      reported. These data can be used for treatment planning. Leakage around the
      applicator was also scored. The dose distributions, PDD, and absolute dose rate
      calculated agree within experimental uncertainties with the doses measured:
      differences of MC data with chamber measurements are up to 0.8% and with
      radiochromic films are up to 3.5%. CONCLUSIONS: The new applicator and the
      dosimetric data provided here will be a valuable tool in clinical practice,
      making treatment of large skin lesions simpler, faster, and safer. Also the dose
      to surrounding healthy tissues is minimal.

PMID- 27036564
TI  - Choroidal vasculature characteristics based choroid segmentation for enhanced
      depth imaging optical coherence tomography images.
AB  - PURPOSE: In clinical research, it is important to measure choroidal thickness
      when eyes are affected by various diseases. The main purpose is to automatically
      segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT)
      images with five B-scans averaging. METHODS: The authors present an automated
      choroid segmentation method based on choroidal vasculature characteristics for
      EDI-OCT images with five B-scans averaging. By considering the large vascular of
      the Haller's layer neighbor with the choroid-sclera junction (CSJ), the authors
      measured the intensity ascending distance and a maximum intensity image in the
      axial direction from a smoothed and normalized EDI-OCT image. Then, based on
      generated choroidal vessel image, the authors constructed the CSJ cost and
      constrain the CSJ search neighborhood. Finally, graph search with smooth
      constraints was utilized to obtain the CSJ boundary. RESULTS: Experimental
      results with 49 images from 10 eyes in 8 normal persons and 270 images from 57
      eyes in 44 patients with several stages of diabetic retinopathy and age-related
      macular degeneration demonstrate that the proposed method can accurately segment
      the choroid of EDI-OCT images with five B-scans averaging. The mean choroid
      thickness difference and overlap ratio between the authors' proposed method and
      manual segmentation drawn by experts were -11.43 MUm and 86.29%, respectively.
      CONCLUSIONS: Good performance was achieved for normal and pathologic eyes, which
      proves that the authors' method is effective for the automated choroid
      segmentation of the EDI-OCT images with five B-scans averaging.

PMID- 27036565
TI  - Automated detection of vessel lumen and stent struts in intravascular optical
      coherence tomography to evaluate stent apposition and neointimal coverage.
AB  - PURPOSE: Intravascular optical coherence tomography (IV-OCT) is a high-resolution
      imaging method used to visualize the microstructure of arterial walls in vivo. IV
      OCT enables the clinician to clearly observe and accurately measure stent
      apposition and neointimal coverage of coronary stents, which are associated with
      side effects such as in-stent thrombosis. In this study, the authors present an
      algorithm for quantifying stent apposition and neointimal coverage by
      automatically detecting lumen contours and stent struts in IV-OCT images.
      METHODS: The algorithm utilizes OCT intensity images and their first and second
      gradient images along the axial direction to detect lumen contours and stent
      strut candidates. These stent strut candidates are classified into true and false
      stent struts based on their features, using an artificial neural network with one
      hidden layer and ten nodes. After segmentation, either the protrusion distance
      (PD) or neointimal thickness (NT) for each strut is measured automatically. In
      randomly selected image sets covering a large variety of clinical scenarios, the
      results of the algorithm were compared to those of manual segmentation by IV-OCT
      readers. RESULTS: Stent strut detection showed a 96.5% positive predictive value
      and a 92.9% true positive rate. In addition, case-by-case validation also showed
      comparable accuracy for most cases. High correlation coefficients (R > 0.99) were
      observed for PD and NT between the algorithmic and the manual results, showing
      little bias (0.20 and 0.46 MUm, respectively) and a narrow range of limits of
      agreement (36 and 54 MUm, respectively). In addition, the algorithm worked well
      in various clinical scenarios and even in cases with a low level of stent
      malapposition and neointimal coverage. CONCLUSIONS: The presented automatic
      algorithm enables robust and fast detection of lumen contours and stent struts
      and provides quantitative measurements of PD and NT. In addition, the algorithm
      was validated using various clinical cases to demonstrate its reliability.
      Therefore, this technique can be effectively utilized for clinical trials on
      stent-related side effects, including in-stent thrombosis and in-stent
      restenosis.

PMID- 27036566
TI  - Reducing false positives of microcalcification detection systems by removal of
      breast arterial calcifications.
AB  - PURPOSE: In the past decades, computer-aided detection (CADe) systems have been
      developed to aid screening radiologists in the detection of malignant
      microcalcifications. These systems are useful to avoid perceptual oversights and
      can increase the radiologists' detection rate. However, due to the high number of
      false positives marked by these CADe systems, they are not yet suitable as an
      independent reader. Breast arterial calcifications (BACs) are one of the most
      frequent false positives marked by CADe systems. In this study, a method is
      proposed for the elimination of BACs as positive findings. Removal of these false
      positives will increase the performance of the CADe system in finding malignant
      microcalcifications. METHODS: A multistage method is proposed for the removal of
      BAC findings. The first stage consists of a microcalcification candidate
      selection, segmentation and grouping of the microcalcifications, and
      classification to remove obvious false positives. In the second stage, a case
      based selection is applied where cases are selected which contain BACs. In the
      final stage, BACs are removed from the selected cases. The BACs removal stage
      consists of a GentleBoost classifier trained on microcalcification features
      describing their shape, topology, and texture. Additionally, novel features are
      introduced to discriminate BACs from other positive findings. RESULTS: The CADe
      system was evaluated with and without BACs removal. Here, both systems were
      applied on a validation set containing 1088 cases of which 95 cases contained
      malignant microcalcifications. After bootstrapping, free-response receiver
      operating characteristics and receiver operating characteristics analyses were
      carried out. Performance between the two systems was compared at 0.98 and 0.95
      specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52%
      and the sensitivity increased from 62% up to 76% at a specificity of 0.95.
      Partial areas under the curve in the specificity range of 0.8-1.0 were
      significantly different between the system without BACs removal and the system
      with BACs removal, 0.129 +/- 0.009 versus 0.144 +/- 0.008 (p<0.05), respectively.
      Additionally, the sensitivity at one false positive per 50 cases and one false
      positive per 25 cases increased as well, 37% versus 51% (p<0.05) and 58% versus
      67% (p<0.05) sensitivity, respectively. Additionally, the CADe system with BACs
      removal reduces the number of false positives per case by 29% on average. The
      same sensitivity at one false positive per 50 cases in the CADe system without
      BACs removal can be achieved at one false positive per 80 cases in the CADe
      system with BACs removal. CONCLUSIONS: By using dedicated algorithms to detect
      and remove breast arterial calcifications, the performance of CADe systems can be
      improved, in particular, at false positive rates representative for operating
      points used in screening.

PMID- 27036567
TI  - Iterative reconstruction for CT perfusion with a prior-image induced hybrid
      nonlocal means regularization: Phantom studies.
AB  - PURPOSE: In computed tomography perfusion (CTP) imaging, an initial phase CT
      acquired with a high-dose protocol can be used to improve the image quality of
      later phase CT acquired with a low-dose protocol. For dynamic regions, signals in
      the later low-dose CT may not be completely recovered if the initial CT heavily
      regularizes the iterative reconstruction process. The authors propose a hybrid
      nonlocal means (hNLM) regularization model for iterative reconstruction of low
      dose CTP to overcome the limitation of the conventional prior-image induced
      penalty. METHODS: The hybrid penalty was constructed by combining the NLM of the
      initial phase high-dose CT in the stationary region and later phase low-dose CT
      in the dynamic region. The stationary and dynamic regions were determined by the
      similarity between the initial high-dose scan and later low-dose scan. The
      similarity was defined as a Gaussian kernel-based distance between the patch
      window of the same pixel in the two scans, and its measurement was then used to
      weigh the influence of the initial high-dose CT. For regions with high similarity
      (e.g., stationary region), initial high-dose CT played a dominant role for
      regularizing the solution. For regions with low similarity (e.g., dynamic
      region), the regularization relied on a low-dose scan itself. This new hNLM
      penalty was incorporated into the penalized weighted least-squares (PWLS) for CTP
      reconstruction. Digital and physical phantom studies were performed to evaluate
      the PWLS-hNLM algorithm. RESULTS: Both phantom studies showed that the PWLS-hNLM
      algorithm is superior to the conventional prior-image induced penalty term
      without considering the signal changes within the dynamic region. In the dynamic
      region of the Catphan phantom, the reconstruction error measured by root mean
      square error was reduced by 42.9% in PWLS-hNLM reconstructed image. CONCLUSIONS:
      The PWLS-hNLM algorithm can effectively use the initial high-dose CT to
      reconstruct low-dose CTP in the stationary region while reducing its influence in
      the dynamic region.

PMID- 27036568
TI  - Fast multipurpose Monte Carlo simulation for proton therapy using multi- and many
      core CPU architectures.
AB  - PURPOSE: Accuracy in proton therapy treatment planning can be improved using
      Monte Carlo (MC) simulations. However the long computation time of such methods
      hinders their use in clinical routine. This work aims to develop a fast
      multipurpose Monte Carlo simulation tool for proton therapy using massively
      parallel central processing unit (CPU) architectures. METHODS: A new Monte Carlo,
      called MCsquare (many-core Monte Carlo), has been designed and optimized for the
      last generation of Intel Xeon processors and Intel Xeon Phi coprocessors. These
      massively parallel architectures offer the flexibility and the computational
      power suitable to MC methods. The class-II condensed history algorithm of
      MCsquare provides a fast and yet accurate method of simulating heavy charged
      particles such as protons, deuterons, and alphas inside voxelized geometries.
      Hard ionizations, with energy losses above a user-specified threshold, are
      simulated individually while soft events are regrouped in a multiple scattering
      theory. Elastic and inelastic nuclear interactions are sampled from ICRU 63
      differential cross sections, thereby allowing for the computation of prompt gamma
      emission profiles. MCsquare has been benchmarked with the gate/geant4 Monte Carlo
      application for homogeneous and heterogeneous geometries. RESULTS: Comparisons
      with gate/geant4 for various geometries show deviations within 2%-1 mm. In spite
      of the limited memory bandwidth of the coprocessor simulation time is below 25 s
      for 10(7) primary 200 MeV protons in average soft tissues using all Xeon Phi and
      CPU resources embedded in a single desktop unit. CONCLUSIONS: MCsquare exploits
      the flexibility of CPU architectures to provide a multipurpose MC simulation
      tool. Optimized code enables the use of accurate MC calculation within a
      reasonable computation time, adequate for clinical practice. MCsquare also
      simulates prompt gamma emission and can thus be used also for in vivo range
      verification.

PMID- 27036569
TI  - Technical Note: Development and performance of a software tool for quality
      assurance of online replanning with a conventional Linac or MR-Linac.
AB  - PURPOSE: To develop an integrated quality assurance (QA) software tool for online
      replanning capable of efficiently and automatically checking radiation treatment
      (RT) planning parameters and gross plan quality, verifying treatment plan data
      transfer from treatment planning system (TPS) to record and verify (R&V) system,
      performing a secondary monitor unit (MU) calculation with or without a presence
      of a magnetic field from MR-Linac, and validating the delivery record consistency
      with the plan. METHODS: The software tool, named ArtQA, was developed to obtain
      and compare plan and treatment parameters from both the TPS and the R&V system
      database. The TPS data are accessed via direct file reading and the R&V data are
      retrieved via open database connectivity and structured query language. Plan
      quality is evaluated with both the logical consistency of planning parameters and
      the achieved dose-volume histograms. Beams in between the TPS and R&V system are
      matched based on geometry configurations. To consider the effect of a 1.5 T
      transverse magnetic field from MR-Linac in the secondary MU calculation, a method
      based on modified Clarkson integration algorithm was developed and tested for a
      series of clinical situations. RESULTS: ArtQA has been used in their clinic and
      can quickly detect inconsistencies and deviations in the entire RT planning
      process. With the use of the ArtQA tool, the efficiency for plan check including
      plan quality, data transfer, and delivery check can be improved by at least 60%.
      The newly developed independent MU calculation tool for MR-Linac reduces the
      difference between the plan and calculated MUs by 10%. CONCLUSIONS: The software
      tool ArtQA can be used to perform a comprehensive QA check from planning to
      delivery with conventional Linac or MR-Linac and is an essential tool for online
      replanning where the QA check needs to be performed rapidly.

PMID- 27036570
TI  - Effects on image quality of a 2D antiscatter grid in x-ray digital breast
      tomosynthesis: Initial experience using the dual modality (x-ray and molecular)
      breast tomosynthesis scanner.
AB  - PURPOSE: Radiation scattered from the breast in digital breast tomosynthesis
      (DBT) causes image degradation, including loss of contrast between cancerous and
      background tissue. Unlike in 2-dimensional (2D) mammography, an antiscatter grid
      cannot readily be used in DBT because changing alignment between the tube and
      detector during the scan would result in unacceptable loss of primary radiation.
      However, in the dual modality breast tomosynthesis (DMT) scanner, which combines
      DBT and molecular breast tomosynthesis, the tube and detector rotate around a
      common axis, thereby maintaining a fixed tube-detector alignment. This C-arm
      geometry raises the possibility of using a 2D (cellular) focused antiscatter
      grid. The purpose of this study is to assess change in image quality when using
      an antiscatter grid in the DBT portion of a DMT scan under conditions of fixed
      radiation dose. METHODS: Two 2D focused prototype grids with 80 cm focal length
      were tested, one stack-laminated from copper (Cu) and one cast from a tungsten
      polymer (W-poly). They were reciprocated using a motion scheme designed to
      maximize transmission of primary x-ray photons. Grid-in and grid-out scatter-to
      primary ratios (SPRs) were measured for rectangular blocks of material simulating
      30%, 50%, and 70% glandular tissue compositions. For assessment of changes in
      image quality through the addition of a grid, the Computerized Imaging Reference
      Systems, Inc., phantom Model 011A containing a set of 1 cm thick blocks
      simulating a range of glandular/adipose ratios from 0/100 to 100/0 was used. To
      simulate 6.5 and 8.5 cm thick compressed breasts, 1 cm thick slices of PMMA were
      added to the Model 011A phantom. DBT images were obtained with and without the
      grid, with exposure parameters fixed for a given compressed thickness. Signal
      difference-to-noise ratios (SDNRs), contrast, and voxel value-based attenuation
      coefficients (MU) were measured for all blocks from reconstructed phantom images.
      RESULTS: For 4, 6, and 8 cm tissue-equivalent block phantom thicknesses, the
      inclusion of the W-poly grid reduced the SPR by factors of 5, 6, and 5.8,
      respectively. For the same thicknesses, the copper grid reduced the SPR by
      factors of 3.9, 4.5, and 4.9. For the 011A phantom, the W-poly grid raised the
      SDNR of the 70/30 block from 0.8, -0.32, and -0.72 to 0.9, 0.76, and 0.062 for
      the 4.5, 6.5, and 8.5 cm phantoms, respectively. It raised the SDNR of the 100/0
      block from 3.78, 1.95, and 1.0 to 3.79, 3.67, and 3.25 for the 4.5, 6.5, and 8.5
      cm phantoms, respectively. Inclusion of the W-poly grid improved the accuracy of
      image-based MU values for all block compositions. However, smearing of
      attenuation across slices due to limited angular sampling decreases the
      sensitivity of voxel values to changing composition compared to theoretical MU
      values. CONCLUSIONS: Under conditions of fixed radiation dose to the breast, use
      of a 2D focused grid increased contrast, SDNR, and accuracy of estimated
      attenuation for mass-simulating block compositions in all phantom thicknesses
      tested, with the degree of improvement depending upon material composition. A 2D
      antiscatter grid can be usefully incorporated in DBT systems that employ fully
      isocentric tube-detector rotation.

PMID- 27036572
TI  - Technical Note: Range verification system using edge detection method for a
      scintillator and a CCD camera system.
AB  - PURPOSE: Three-dimensional irradiation with a scanned carbon-ion beam has been
      performed from 2011 at the authors' facility. The authors have developed the
      rotating-gantry equipped with the scanning irradiation system. The number of
      combinations of beam properties to measure for the commissioning is more than
      7200, i.e., 201 energy steps, 3 intensities, and 12 gantry angles. To compress
      the commissioning time, quick and simple range verification system is required.
      In this work, the authors develop a quick range verification system using
      scintillator and charge-coupled device (CCD) camera and estimate the accuracy of
      the range verification. METHODS: A cylindrical plastic scintillator block and a
      CCD camera were installed on the black box. The optical spatial resolution of the
      system is 0.2 mm/pixel. The camera control system was connected and communicates
      with the measurement system that is part of the scanning system. The range was
      determined by image processing. Reference range for each energy beam was
      determined by a difference of Gaussian (DOG) method and the 80% of distal dose of
      the depth-dose distribution that were measured by a large parallel-plate
      ionization chamber. The authors compared a threshold method and a DOG method.
      RESULTS: The authors found that the edge detection method (i.e., the DOG method)
      is best for the range detection. The accuracy of range detection using this
      system is within 0.2 mm, and the reproducibility of the same energy measurement
      is within 0.1 mm without setup error. CONCLUSIONS: The results of this study
      demonstrate that the authors' range check system is capable of quick and easy
      range verification with sufficient accuracy.

PMID- 27036571
TI  - A model-based scatter artifacts correction for cone beam CT.
AB  - PURPOSE: Due to the increased axial coverage of multislice computed tomography
      (CT) and the introduction of flat detectors, the size of x-ray illumination
      fields has grown dramatically, causing an increase in scatter radiation. For CT
      imaging, scatter is a significant issue that introduces shading artifact,
      streaks, as well as reduced contrast and Hounsfield Units (HU) accuracy. The
      purpose of this work is to provide a fast and accurate scatter artifacts
      correction algorithm for cone beam CT (CBCT) imaging. METHODS: The method starts
      with an estimation of coarse scatter profiles for a set of CBCT data in either
      image domain or projection domain. A denoising algorithm designed specifically
      for Poisson signals is then applied to derive the final scatter distribution.
      Qualitative and quantitative evaluations using thorax and abdomen phantoms with
      Monte Carlo (MC) simulations, experimental Catphan phantom data, and in vivo
      human data acquired for a clinical image guided radiation therapy were performed.
      Scatter correction in both projection domain and image domain was conducted and
      the influences of segmentation method, mismatched attenuation coefficients, and
      spectrum model as well as parameter selection were also investigated. RESULTS:
      Results show that the proposed algorithm can significantly reduce scatter
      artifacts and recover the correct HU in either projection domain or image domain.
      For the MC thorax phantom study, four-components segmentation yields the best
      results, while the results of three-components segmentation are still acceptable.
      The parameters (iteration number K and weight beta) affect the accuracy of the
      scatter correction and the results get improved as K and beta increase. It was
      found that variations in attenuation coefficient accuracies only slightly impact
      the performance of the proposed processing. For the Catphan phantom data, the
      mean value over all pixels in the residual image is reduced from -21.8 to -0.2 HU
      and 0.7 HU for projection domain and image domain, respectively. The contrast of
      the in vivo human images is greatly improved after correction. CONCLUSIONS: The
      software-based technique has a number of advantages, such as high computational
      efficiency and accuracy, and the capability of performing scatter correction
      without modifying the clinical workflow (i.e., no extra scan/measurement data are
      needed) or modifying the imaging hardware. When implemented practically, this
      should improve the accuracy of CBCT image quantitation and significantly impact
      CBCT-based interventional procedures and adaptive radiation therapy.

PMID- 27036573
TI  - Technical Note: Effect of explicit M and N-shell atomic transitions on a low
      energy x-ray source.
AB  - PURPOSE: In EGSnrc, atomic transitions to and from the M and N-shells are treated
      in an average way by default. This approach is justified in which the energy
      difference between explicit and average M and N-shell binding energies is less
      than 1 keV, and for most applications can be considered negligible. However, for
      simulations of low energy x-ray sources on thin, high-Z targets, characteristic x
      rays can make up a significant portion of the source spectra. As of release V4
      2.4.0, EGSnrc has included an option to enable a more complete algorithm of all
      atomic transitions available in the EADL compilation. In this paper, the effect
      of M and N-shell averaging on the calculation of half-value layer (HVL) and
      relative depth dose (RDD) curve of a 50 kVp intraoperative x-ray tube with a thin
      gold target was investigated. METHODS: A 50 kVp miniature x-ray source with a
      gold target (The INTRABEAM System, Carl Zeiss, Germany) was modeled with the
      EGSnrc user code cavity, both with and without M and N-shell averaging. From
      photon fluence spectra simulations, the source HVLs were determined analytically.
      The same source model was then used with egs_chamber to calculate RDD curves in
      water. RESULTS: A 4% increase of HVL was reported when accounting for explicit M
      and N-shell transitions, and up to a 9% decrease in local relative dose for
      normalization at 3 mm depth in water. CONCLUSIONS: The EGSnrc default of using
      averaged M and N-shell binding energies has an observable effect on the HVL and
      RDD of a low energy x-ray source with high-Z target. For accurate modeling of
      this class of devices, explicit atomic transitions should be included.

PMID- 27036574
TI  - Physical modeling of microwave ablation zone clinical margin variance.
AB  - PURPOSE: The objective of this study is to measure through simulation the impact
      of (1) heterogeneity of biophysical parameters in tumor vs healthy tissue, (2)
      applicator placement relative to the tumor, and (3) proximity to large blood
      vessels on microwave ablation (MWA) treatment effect area. This will help
      identify the biophysical properties that have the greatest impact on improving
      clinical modeling of MWA procedures. METHODS: The authors' approach was to
      develop two-compartment models with variable tissue properties and simulate MWA
      procedures performed in liver with Perseon Medical's 915 MHz short-tip
      applicator. Input parameters for the dielectric and thermal properties considered
      in this study were based on measurements for healthy and malignant (primary or
      metastatic) liver tissue previously reported in the literature. Compartment 1
      (C1) represented normal, fatty, or cirrhotic liver, and compartment 2 (C2)
      represented a primary hepatocellular carcinoma tumor sample embedded within C1.
      To evaluate the sensitivity to tissue parameters, a range of clinically relevant
      tissue properties were simulated. To evaluate the impact of MWA antenna position,
      the authors simulated various tumor perfusion models with the antenna shifted 5
      mm anteriorly and posteriorly. To evaluate the effect of local vasculature, the
      authors simulated an additional heat sink of various diameters and distances from
      the tumor. Dice coefficient statistics were used to evaluate ablation zone
      effects from these local heat sinks. RESULTS: Models showed less than 11% of
      volume variability (1 cm(3) increase) in ablation treatment effect region when
      accounting for the difference in relative permittivity and electrical
      conductivity between malignant and healthy liver tissue. There was a 27% increase
      in volume when simulating thermal conductivity of fatty liver disease versus the
      baseline simulation. The ablation zone volume increased more than 36% when
      simulating cirrhotic surrounding liver tissue. Antenna placement relative to the
      tumor had minimal sensitivity to the absolute size of the treatment effect area,
      with less than 1.5 mm variation. However, when considering the overlap between
      the ablation zone and the ideal clinical margin when the antenna was displaced 5
      mm anteriorly and posteriorly, there was approximately a 6 mm difference in the
      margins. Dice coefficient statistics showed as much as an 11% decrease in the
      ablation margin due to the presence of vessel heat sinks within the model.
      CONCLUSIONS: The results from simulating the variance in malignant tissue thermal
      and electrical properties will help guide better approximations for MWA
      treatments. The results suggest that assuming malignant and healthy liver tissues
      have similar dielectric properties is a reasonable first approximation. Antenna
      placement relative to the tumor has minimal impact on the absolute size of the
      ablation zone, yet it does cause relevant variation between desired treatment
      margin and ablation zone. Blood vessel cooling, especially hepatic vessels close
      to the region of interest, may be a significant factor to consider in treatment
      planning. Further data need to be collected for assessing treatment planning
      utility of modeling MWA in this context.

PMID- 27036575
TI  - Multilevel segmentation of intracranial aneurysms in CT angiography images.
AB  - PURPOSE: Segmentation of aneurysms plays an important role in interventional
      planning. Yet, the segmentation of both the lumen and the thrombus of an
      intracranial aneurysm in computed tomography angiography (CTA) remains a
      challenge. This paper proposes a multilevel segmentation methodology for
      efficiently segmenting intracranial aneurysms in CTA images. METHODS: The
      proposed methodology first uses the lattice Boltzmann method (LBM) to extract the
      lumen part directly from the original image. Then, the LBM is applied again on an
      intermediate image whose lumen part is filled by the mean gray-level value
      outside the lumen, to yield an image region containing part of the aneurysm
      boundary. After that, an expanding disk is introduced to estimate the complete
      contour of the aneurysm. Finally, the contour detected is used as the initial
      contour of the level set with ellipse to refine the aneurysm. RESULTS: The
      results obtained on 11 patients from different hospitals showed that the proposed
      segmentation was comparable with manual segmentation, and that quantitatively,
      the average segmentation matching factor (SMF) reached 86.99%, demonstrating good
      segmentation accuracy. Chan-Vese method, Sen's model, and Luca's model were used
      to compare the proposed method and their average SMF values were 39.98%, 40.76%,
      and 77.11%, respectively. CONCLUSIONS: The authors have presented a multilevel
      segmentation method based on the LBM and level set with ellipse for accurate
      segmentation of intracranial aneurysms. Compared to three existing methods, for
      all eleven patients, the proposed method can successfully segment the lumen with
      the highest SMF values for nine patients and second highest SMF values for the
      two. It also segments the entire aneurysm with the highest SMF values for ten
      patients and second highest SMF value for the one. This makes it potential for
      clinical assessment of the volume and aspect ratio of the intracranial aneurysms.

PMID- 27036576
TI  - Benefits of adaptive radiation therapy in lung cancer as a function of replanning
      frequency.
AB  - PURPOSE: To quantify the potential benefit associated with daily replanning in
      lung cancer in terms of normal tissue dose sparing and to characterize the
      tradeoff between adaptive benefit and replanning frequency. METHODS: A set of
      synthetic images and contours, derived from weekly active breathing control
      images of 12 patients who underwent radiation therapy treatment for nonsmall cell
      lung cancer, is generated for each fraction of treatment using principal
      component analysis in a way that preserves temporal anatomical trends (e.g.,
      tumor regression). Daily synthetic images and contours are used to simulate four
      different treatment scenarios: (1) a "no-adapt" scenario that simulates delivery
      of an initial plan throughout treatment, (2) a "midadapt" scenario that
      implements a single replan for fraction 18, (3) a "weekly adapt" scenario that
      simulates weekly adaptations, and (4) a "full-adapt" scenario that simulates
      daily replanning. An initial intensity modulated radiation therapy plan is
      created for each patient and replanning is carried out in an automated fashion by
      reoptimizing beam apertures and weights. Dose is calculated on each image and
      accumulated to the first in the series using deformable mappings utilized in
      synthetic image creation for comparison between simulated treatments. RESULTS:
      Target coverage was maintained and cord tolerance was not exceeded for any of the
      adaptive simulations. Average reductions in mean lung dose (MLD) and volume of
      lung receiving 20 Gy or more (V20lung) were 65 +/- 49 cGy (p = 0.000 01) and 1.1%
      +/- 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in
      MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the
      target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal
      dose (MED), dose received by 66% of the heart (D66heart), and dose received by
      33% of the heart (D33heart), were 158 +/- 280, 117 +/- 121, 37 +/- 77, and 99 +/-
      120 cGy, respectively. Average incremental reductions in MLD for the midadapt,
      weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively.
      Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy.
      Reductions in MLD and MED for the full-adapt treatment were correlated with the
      absolute decrease in the planning target volume (r = 0.34 and r = 0.26).
      CONCLUSIONS: Adaptive radiation therapy for lung cancer yields clinically
      relevant reductions in normal tissue doses for frequencies of adaptation ranging
      from a single replan up to daily replanning. Increased frequencies of adaptation
      result in additional benefit while magnitude of benefit decreases.

PMID- 27036577
TI  - Ultrasound intima-media thickness measurement of the carotid artery using ant
      colony optimization combined with a curvelet-based orientation-selective filter.
AB  - PURPOSE: Automatic measurement of the intima-media thickness (IMT) from
      ultrasound carotid images is an important task in clinical diagnosis. Many
      computer-based techniques for IMT measurement have been proposed to overcome the
      limits of manual segmentation. However, the robustness of the algorithms would be
      influenced by the inherent speckle noise of ultrasound image. This paper proposed
      a curvelet guided ant colony optimization (CGACO) strategy that could achieve
      satisfied accuracy for IMT measurement with improved robustness to noise.
      METHODS: The curvelet-based orientation-selective (CBOS) filter was first
      introduced for speckle removal and edge enhancement. Different from conventional
      methods, CBOS filter processes the curvelet coefficients by orientations rather
      than by magnitude. Then, a specially designed two-leg ant colony optimization
      technique, combined with Otsu thresholding and Sobel edge detector, was proposed
      as a novel segmentation method to extract the media-adventitia (MA) and the lumen
      intima (LI) boundaries. Finally, a coupled snake model was employed to further
      smooth the contours of MA and LI. RESULTS: In addition to 224 carotid artery
      images acquired from 34 participants, simulated speckled images with nine levels
      of noise were also included in the database. The mean absolute distance errors of
      CGACO for LI interface tracings, MA interface tracings, and IMT measurements were
      0.030 +/- 0.027, 0.039 +/- 0.036, and 0.041 +/- 0.036 mm, respectively. Besides,
      CGACO had a correlation coefficient as high as 0.992 and a bias as low as -0.008.
      All these measures were comparable to or better than a previous technique and the
      manual segmentation. On the other hand, CGACO had the highest success rate of
      98.7% in the segmentation of real data. It also maintained a much higher success
      rate in the segmentation of simulated images with different levels of speckle
      noise. CONCLUSIONS: The proposed technique showed accurate IMT measurement
      results. Furthermore, benefiting from the CBOS filter, the robustness to noise of
      the algorithm was substantially improved. Therefore, CGACO could provide a
      reliable way to segment the carotid artery from ultrasound images and could be
      used in clinical practice of IMT measurement, particularly in early
      atherosclerotic stages.

PMID- 27036578
TI  - Volume of interest CBCT and tube current modulation for image guidance using
      dynamic kV collimation.
AB  - PURPOSE: The focus of this work is the development of a novel blade collimation
      system enabling volume of interest (VOI) CBCT with tube current modulation using
      the kV image guidance source on a linear accelerator. Advantages of the system
      are assessed, particularly with regard to reduction and localization of dose and
      improvement of image quality. METHODS: A four blade dynamic kV collimator was
      developed to track a VOI during a CBCT acquisition. The current prototype is
      capable of tracking an arbitrary volume defined by the treatment planner for
      subsequent CBCT guidance. During gantry rotation, the collimator tracks the VOI
      with adjustment of position and dimension. CBCT image quality was investigated as
      a function of collimator dimension, while maintaining the same dose to the VOI,
      for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert
      centered on isocenter. Dose distributions were modeled using a dynamic BEAMnrc
      library and DOSXYZnrc. The resulting VOI dose distributions were compared to full
      field CBCT distributions to quantify dose reduction and localization to the
      target volume. A novel method of optimizing x-ray tube current during CBCT
      acquisition was developed and assessed with regard to contrast-to-noise ratio
      (CNR) and imaging dose. RESULTS: Measurements show that the VOI CBCT method using
      the dynamic blade system yields an increase in contrast-to-noise ratio by a
      factor of approximately 2.2. Depending upon the anatomical site, dose was reduced
      to 15%-80% of the full-field CBCT value along the central axis plane and down to
      less than 1% out of plane. The use of tube current modulation allowed for
      specification of a desired SNR within projection data. For approximately the same
      dose to the VOI, CNR was further increased by a factor of 1.2 for modulated VOI
      CBCT, giving a combined improvement of 2.6 compared to full-field CBCT.
      CONCLUSIONS: The present dynamic blade system provides significant improvements
      in CNR for the same imaging dose and localization of imaging dose to a predefined
      volume of interest. The approach is compatible with tube current modulation,
      allowing optimization of the imaging protocol.

PMID- 27036579
TI  - Detailed evaluation of an automated approach to interactive optimization for
      volumetric modulated arc therapy plans.
AB  - PURPOSE: Interactive optimization during treatment planning requires intermittent
      adjustment of organ-at-risk (OAR) objectives relative to the dose-volume
      histogram line. This is a labor-intensive process and the resulting plans are
      prone to variations in quality. The authors' in-house developed approach to
      automated interactive optimization (AIO) automatically moves the mouse cursor to
      adjust the position of on-screen optimization objectives. This allows for the use
      of more objectives per OAR and results in a more frequent and consistent
      adjustment of these objectives during optimization. The authors report a detailed
      evaluation of AIO performance in support of its implementation for routine head
      and neck cancer (HNC) planning and an evaluation for locally advanced lung cancer
      (LC) planning which requires a different optimization strategy. METHODS:
      Volumetric modulated arc therapy AIO plans (APs) were created for 70 HNC patients
      with a simultaneously integrated boost and 20 LC patients and benchmarked against
      their respective manually interactively optimized plans (MPs). The same set of
      optimization objectives and priorities was used for all APs, although planning
      target volume (PTV) optimization priorities could be increased manually in a
      subsequent "continue previous optimization" calculation. HNC plans were
      benchmarked using mean dose to individual and composite OARs and elective/boost
      PTV (PTVE/PTVB) volumes receiving 95% and 107% of the prescription dose (V95% and
      V107%, respectively). A clinician performed blinded comparison of 20 APs and
      respective MPs. LC plans were compared using PTV V95%/V107%, contralateral lung
      (CL) volume receiving 5 Gy (V5Gy), total lung (TL)-PTV V5Gy/V20Gy, and esophagus
      and heart V40Gy/V60Gy/mean doses. RESULTS: For HNC, statistically significant
      improvements in sparing of all OARs, except for the ipsilateral submandibular
      gland and trachea, were obtained in the APs compared to MPs. Average mean dose to
      oral cavity, composite salivary, and swallowing structures were 25.4/23.8,
      24.2/23.2, and 29.5/25.5 Gy, respectively, for the MPs/APs. PTV heterogeneity was
      similar: in the APs, PTVB V95% was 0.2% higher while PTV B/PTV E V107% was
      0.4%/1.0% lower. In 19 out of 20 HNC patients, the clinician preferred the AP,
      mainly because of better OAR sparing and PTV dose homogeneity. For LC, APs had a
      significantly lower CL V5Gy (6.1%), heart mean dose/V60Gy (0.9 Gy/1.2%) and
      esophagus mean dose/V60Gy (0.9 Gy/2.8%), a nonsignificantly higher TL V20Gy
      (1.4%), and a slight, but significantly higher dose deposition to the body. PTV
      dose coverage and homogeneity were similar in the APs and MPs. AIO was considered
      sufficiently robust for clinical use in LC. CONCLUSIONS: HNC and LC APs were at
      least as good as, and often of improved quality over MPs. To date, AIO has been
      clinically implemented for HNC planning.

PMID- 27036580
TI  - Patient motion effects on the quantification of regional myocardial blood flow
      with dynamic PET imaging.
AB  - PURPOSE: Patient motion is a common problem during dynamic positron emission
      tomography (PET) scans for quantification of myocardial blood flow (MBF). The
      purpose of this study was to quantify the prevalence of body motion in a clinical
      setting and evaluate with realistic phantoms the effects of motion on blood flow
      quantification, including CT attenuation correction (CTAC) artifacts that result
      from PET-CT misalignment. METHODS: A cohort of 236 sequential patients was
      analyzed for patient motion under resting and peak stress conditions by two
      independent observers. The presence of motion, affected time-frames, and
      direction of motion was recorded; discrepancy between observers was resolved by
      consensus review. Based on these results, patient body motion effects on MBF
      quantification were characterized using the digital NURBS-based cardiac-torso
      phantom, with characteristic time activity curves (TACs) assigned to the heart
      wall (myocardium) and blood regions. Simulated projection data were corrected for
      attenuation and reconstructed using filtered back-projection. All simulations
      were performed without noise added, and a single CT image was used for
      attenuation correction and aligned to the early- or late-frame PET images.
      RESULTS: In the patient cohort, mild motion of 0.5 +/- 0.1 cm occurred in 24% and
      moderate motion of 1.0 +/- 0.3 cm occurred in 38% of patients. Motion in the
      superior/inferior direction accounted for 45% of all detected motion, with 30% in
      the superior direction. Anterior/posterior motion was predominant (29%) in the
      posterior direction. Left/right motion occurred in 24% of cases, with similar
      proportions in the left and right directions. Computer simulation studies
      indicated that errors in MBF can approach 500% for scans with severe patient
      motion (up to 2 cm). The largest errors occurred when the heart wall was shifted
      left toward the adjacent lung region, resulting in a severe undercorrection for
      attenuation of the heart wall. Simulations also indicated that the magnitude of
      MBF errors resulting from motion in the superior/inferior and anterior/posterior
      directions was similar (up to 250%). Body motion effects were more detrimental
      for higher resolution PET imaging (2 vs 10 mm full-width at half-maximum), and
      for motion occurring during the mid-to-late time-frames. Motion correction of the
      reconstructed dynamic image series resulted in significant reduction in MBF
      errors, but did not account for the residual PET-CTAC misalignment artifacts. MBF
      bias was reduced further using global partial-volume correction, and using
      dynamic alignment of the PET projection data to the CT scan for accurate
      attenuation correction during image reconstruction. CONCLUSIONS: Patient body
      motion can produce MBF estimation errors up to 500%. To reduce these errors, new
      motion correction algorithms must be effective in identifying motion in the
      left/right direction, and in the mid-to-late time-frames, since these conditions
      produce the largest errors in MBF, particularly for high resolution PET imaging.
      Ideally, motion correction should be done before or during image reconstruction
      to eliminate PET-CTAC misalignment artifacts.

PMID- 27036581
TI  - Radiation dose and cancer risk to out-of-field and partially in-field organs from
      radiotherapy for symptomatic vertebral hemangiomas.
AB  - PURPOSE: Vertebral hemangiomas (VHs) are the most common benign tumors of the
      spine that may cause bone resorption. Megavoltage irradiation is usually the
      treatment of choice for the management of symptomatic VHs. The current study was
      conducted to estimate the risk for carcinogenesis from radiotherapy of this
      benign disease on the basis of the calculated radiation doses to healthy organs.
      METHODS: The Monte Carlo N-particle transport code was employed to simulate the
      irradiation with 6 MV x-rays of a VH presented in the cervical, upper thoracic,
      lower thoracic, and lumbar spine. The average radiation dose (Dav) received by
      each critical organ located outside the primarily irradiated area was calculated.
      Three-dimensional treatment plans were also generated for the VHs occurring at
      the four different sites of the spinal cord based on patients' computed
      tomography data. The organ equivalent dose (OED) to each radiosensitive
      structure, which was partly encompassed by the applied treatment fields, was
      calculated with the aid of differential dose-volume histograms. The Dav and the
      OED values were combined with a linear-no-threshold model and a nonlinear
      mechanistic model, respectively, to estimate the organ-, age-, and gender
      specific lifetime attributable risks (LARs) for cancer development. The estimated
      risks were compared with the respective nominal lifetime intrinsic risks (LIRs)
      for the unexposed population. RESULTS: For a standard target dose of 34 Gy, the
      OED varied from 0.39-5.15 Gy by the organ of interest and the irradiation site.
      The Dav range for the out-of-field organs was 4.9 * 10(-4) to 0.56 Gy. The LAR
      for the appearance of malignancies in the partially in-field organs after
      radiotherapy of male and female patients was (0.08%-1.8%) and (0.09%-1.9%),
      respectively. These risk values were 1.5-15.5 times lower when compared to the
      respective LIRs. The lifetime probability for out-of-field cancer induction in
      irradiated males and females was (2.5 * 10(-4) to 7.7 * 10(-2))% and (1.4 * 10(
      4) to 2.6 * 10(-1))%, respectively. The above risks were one to four orders of
      magnitude lower than the LIRs. CONCLUSIONS: The probability for the development
      of out-of-field malignancies due to radiotherapy for VHs is trivial with respect
      to the nominal risk for unexposed population. The respective cancer risks to
      partially in-field organs are smaller than the nominal probabilities but they
      should not be considered as inconsiderable. These risks may be taken into account
      during the follow-up of patients treated for a symptomatic VH.

PMID- 27036582
TI  - Accelerated fast iterative shrinkage thresholding algorithms for sparsity
      regularized cone-beam CT image reconstruction.
AB  - PURPOSE: The development of iterative image reconstruction algorithms for cone
      beam computed tomography (CBCT) remains an active and important research area.
      Even with hardware acceleration, the overwhelming majority of the available 3D
      iterative algorithms that implement nonsmooth regularizers remain computationally
      burdensome and have not been translated for routine use in time-sensitive
      applications such as image-guided radiation therapy (IGRT). In this work, two
      variants of the fast iterative shrinkage thresholding algorithm (FISTA) are
      proposed and investigated for accelerated iterative image reconstruction in CBCT.
      METHODS: Algorithm acceleration was achieved by replacing the original gradient
      descent step in the FISTAs by a subproblem that is solved by use of the ordered
      subset simultaneous algebraic reconstruction technique (OS-SART). Due to the
      preconditioning matrix adopted in the OS-SART method, two new weighted proximal
      problems were introduced and corresponding fast gradient projection-type
      algorithms were developed for solving them. We also provided efficient numerical
      implementations of the proposed algorithms that exploit the massive data
      parallelism of multiple graphics processing units. RESULTS: The improved rates of
      convergence of the proposed algorithms were quantified in computer-simulation
      studies and by use of clinical projection data corresponding to an IGRT study.
      The accelerated FISTAs were shown to possess dramatically improved convergence
      properties as compared to the standard FISTAs. For example, the number of
      iterations to achieve a specified reconstruction error could be reduced by an
      order of magnitude. Volumetric images reconstructed from clinical data were
      produced in under 4 min. CONCLUSIONS: The FISTA achieves a quadratic convergence
      rate and can therefore potentially reduce the number of iterations required to
      produce an image of a specified image quality as compared to first-order methods.
      We have proposed and investigated accelerated FISTAs for use with two nonsmooth
      penalty functions that will lead to further reductions in image reconstruction
      times while preserving image quality. Moreover, with the help of a mixed sparsity
      regularization, better preservation of soft-tissue structures can be potentially
      obtained. The algorithms were systematically evaluated by use of computer
      simulated and clinical data sets.

PMID- 27036583
TI  - Influence of amplitude-related perfusion parameters in the parotid glands by non
      fat-saturated dynamic contrast-enhanced magnetic resonance imaging.
AB  - PURPOSE: To verify whether quantification of parotid perfusion is affected by fat
      signals on non-fat-saturated (NFS) dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) and whether the influence of fat is reduced with fat saturation
      (FS). METHODS: This study consisted of three parts. First, a retrospective study
      analyzed DCE-MRI data previously acquired on different patients using NFS (n =
      18) or FS (n = 18) scans. Second, a phantom study simulated the signal
      enhancements in the presence of gadolinium contrast agent at six concentrations
      and three fat contents. Finally, a prospective study recruited nine healthy
      volunteers to investigate the influence of fat suppression on perfusion
      quantification on the same subjects. Parotid perfusion parameters were derived
      from NFS and FS DCE-MRI data using both pharmacokinetic model analysis and
      semiquantitative parametric analysis. T tests and linear regression analysis were
      used for statistical analysis with correction for multiple comparisons. RESULTS:
      NFS scans showed lower amplitude-related parameters, including parameter A, peak
      enhancement (PE), and slope than FS scans in the patients (all with P < 0.0167).
      The relative signal enhancement in the phantoms was proportional to the dose of
      contrast agent and was lower in NFS scans than in FS scans. The volunteer study
      showed lower parameter A (6.75 +/- 2.38 a.u.), PE (42.12% +/- 14.87%), and slope
      (1.43% +/- 0.54% s(-1)) in NFS scans as compared to 17.63 +/- 8.56 a.u., 104.22%
      +/- 25.15%, and 9.68% +/- 1.67% s(-1), respectively, in FS scans (all with P <
      0.005). These amplitude-related parameters were negatively associated with the
      fat content in NFS scans only (all with P < 0.05). CONCLUSIONS: On NFS DCE-MRI,
      quantification of parotid perfusion is adversely affected by the presence of fat
      signals for all amplitude-related parameters. The influence could be reduced on
      FS scans.

PMID- 27036584
TI  - Urinary bladder segmentation in CT urography using deep-learning convolutional
      neural network and level sets.
AB  - PURPOSE: The authors are developing a computerized system for bladder
      segmentation in CT urography (CTU) as a critical component for computer-aided
      detection of bladder cancer. METHODS: A deep-learning convolutional neural
      network (DL-CNN) was trained to distinguish between the inside and the outside of
      the bladder using 160 000 regions of interest (ROI) from CTU images. The trained
      DL-CNN was used to estimate the likelihood of an ROI being inside the bladder for
      ROIs centered at each voxel in a CTU case, resulting in a likelihood map.
      Thresholding and hole-filling were applied to the map to generate the initial
      contour for the bladder, which was then refined by 3D and 2D level sets. The
      segmentation performance was evaluated using 173 cases: 81 cases in the training
      set (42 lesions, 21 wall thickenings, and 18 normal bladders) and 92 cases in the
      test set (43 lesions, 36 wall thickenings, and 13 normal bladders). The
      computerized segmentation accuracy using the DL likelihood map was compared to
      that using a likelihood map generated by Haar features and a random forest
      classifier, and that using our previous conjoint level set analysis and
      segmentation system (CLASS) without using a likelihood map. All methods were
      evaluated relative to the 3D hand-segmented reference contours. RESULTS: With DL
      CNN-based likelihood map and level sets, the average volume intersection ratio,
      average percent volume error, average absolute volume error, average minimum
      distance, and the Jaccard index for the test set were 81.9% +/- 12.1%, 10.2% +/-
      16.2%, 14.0% +/- 13.0%, 3.6 +/- 2.0 mm, and 76.2% +/- 11.8%, respectively. With
      the Haar-feature-based likelihood map and level sets, the corresponding values
      were 74.3% +/- 12.7%, 13.0% +/- 22.3%, 20.5% +/- 15.7%, 5.7 +/- 2.6 mm, and 66.7%
      +/- 12.6%, respectively. With our previous CLASS with local contour refinement
      (LCR) method, the corresponding values were 78.0% +/- 14.7%, 16.5% +/- 16.8%,
      18.2% +/- 15.0%, 3.8 +/- 2.3 mm, and 73.9% +/- 13.5%, respectively. CONCLUSIONS:
      The authors demonstrated that the DL-CNN can overcome the strong boundary between
      two regions that have large difference in gray levels and provides a seamless
      mask to guide level set segmentation, which has been a problem for many gradient
      based segmentation methods. Compared to our previous CLASS with LCR method, which
      required two user inputs to initialize the segmentation, DL-CNN with level sets
      achieved better segmentation performance while using a single user input.
      Compared to the Haar-feature-based likelihood map, the DL-CNN-based likelihood
      map could guide the level sets to achieve better segmentation. The results
      demonstrate the feasibility of our new approach of using DL-CNN in combination
      with level sets for segmentation of the bladder.

PMID- 27036585
TI  - An 8-channel RF coil array for carotid artery MR imaging in humans at 3 T.
AB  - PURPOSE: Carotid artery diseases due to plaque buildup at the carotid bifurcation
      are a leading cause of stroke. Accurate plaque quantification and
      characterization of plaque composition and morphology by magnetic resonance
      imaging (MRI) is essential to identifying high-risk patients. Difficulties in
      detecting plaque, which is physically small, and the unique physiological
      structure of the carotid artery make use of a radio frequency (RF) coil array
      with high resolution, large longitudinal coverage, and deep penetration ideal for
      clinical examinations. The goal of this project was to design and fabricate a
      sensitive RF coil array with sufficient imaging coverage and signal-to-noise
      ratio (SNR) for carotid artery imaging at 3 T. METHODS: Based on clinical
      requirements and the anatomical structure of the human carotid artery, an 8
      channel carotid coil array was designed and fabricated for 3 T MRI of the carotid
      artery in humans. The performance of the proposed 8-channel carotid coil array
      was validated through bench tests and MR imaging experiments on a 3 T whole body
      MRI scanner. Its performance was also compared experimentally to the performance
      of a commercial 4-channel phased array carotid coil designed by Machnet BV
      (Machnet BV coil, Roden, Netherlands). RESULTS: The 8-channel carotid coil array
      performed significantly better in imaging the carotid artery than the commercial
      4-channel Machnet BV coil in terms of the SNR, coverage, and penetration depth.
      In parallel imaging, the proposed 8-channel carotid coil array demonstrated a
      much lower maximum value and average value of the geometry factor in the region
      of interest. Carotid artery images acquired in vivo using the proposed 8-channel
      carotid artery coil and the commercial 4-channel Machnet BV coil were also
      compared, demonstrating the former's potential for clinical diagnosis.
      CONCLUSIONS: Based on the analyses of phantom and in vivo imaging studies, the
      proposed 8-channel carotid coil array has the potential for use in clinical
      diagnosis, performing better in terms of SNR, imaging coverage, and penetration
      depth than the commercial 4-channel carotid artery coil array at 3 T. In future
      studies, the proposed 8-channel carotid coil array can also serve as an important
      part of a large-scale multichannel coil array for imaging the whole carotid
      artery system, including the extracranial and intracranial arteries.

PMID- 27036586
TI  - Multivariate analysis for the estimation of target localization errors in
      fiducial marker-based radiotherapy.
AB  - PURPOSE: To assess the target localization error (TLE) in terms of the distance
      between the target and the localization point estimated from the surrogates
      (|TMD|), the average of respiratory motion for the surrogates and the target
      (|aRM|), and the number of fiducial markers used for estimating the target (n).
      METHODS: This study enrolled 17 lung cancer patients who subsequently underwent
      four fractions of real-time tumor tracking irradiation. Four or five fiducial
      markers were implanted around the lung tumor. The three-dimensional (3D) distance
      between the tumor and markers was at maximum 58.7 mm. One of the markers was used
      as the target (Pt), and those markers with a 3D |TMDn| <= 58.7 mm at end
      exhalation were then selected. The estimated target position (Pe) was calculated
      from a localization point consisting of one to three markers except Pt.
      Respiratory motion for Pt and Pe was defined as the root mean square of each
      displacement, and |aRM| was calculated from the mean value. TLE was defined as
      the root mean square of each difference between Pt and Pe during the monitoring
      of each fraction. These procedures were performed repeatedly using the remaining
      markers. To provide the best guidance on the answer with n and |TMD|, fiducial
      markers with a 3D |aRM >= 10 mm were selected. Finally, a total of 205, 282, and
      76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n =
      1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to
      evaluate TLE as a function of |TMD| and |aRM| in each n. RESULTS: |TMD| for n = 1
      was larger than that for n = 3. Moreover, |aRM| was almost constant for all n,
      indicating a similar scale for the marker's motion near the lung tumor. MRA
      showed that |aRM| in the left-right direction was the major cause of TLE;
      however, the contribution made little difference to the 3D TLE because of the
      small amount of motion in the left-right direction. The TLE calculated from the
      MRA ((MRA)TLE) increased as |TMD| and |aRM| increased and adversely decreased
      with each increment of n. The median 3D (MRA)TLE was 2.0 mm (range, 0.6-4.3 mm)
      for n = 1, 1.8 mm (range, 0.4-4.0 mm) for n = 2, and 1.6 mm (range, 0.3-3.7 mm)
      for n = 3. Although statistical significance between n = 1 and n = 3 was observed
      in all directions, the absolute average difference and the standard deviation of
      the (MRA)TLE between n = 1 and n = 3 were 0.5 and 0.2 mm, respectively.
      CONCLUSIONS: A large |TMD| and |aRM| increased the differences in TLE between
      each n; however, the difference in 3D (MRA)TLEs was, at most, 0.6 mm. Thus, the
      authors conclude that it is acceptable to continue fiducial marker-based
      radiotherapy as long as |TMD| is maintained at <=58.7 mm for a 3D |aRM|  >=  10
      mm.

PMID- 27036587
TI  - Simulation of pseudo-CT images based on deformable image registration of
      ultrasound images: A proof of concept for transabdominal ultrasound imaging of
      the prostate during radiotherapy.
AB  - PURPOSE: Imaging of patient anatomy during treatment is a necessity for position
      verification and for adaptive radiotherapy based on daily dose recalculation.
      Ultrasound (US) image guided radiotherapy systems are currently available to
      collect US images at the simulation stage (USsim), coregistered with the
      simulation computed tomography (CT), and during all treatment fractions. The
      authors hypothesize that a deformation field derived from US-based deformable
      image registration can be used to create a daily pseudo-CT (CTps) image that is
      more representative of the patients' geometry during treatment than the CT
      acquired at simulation stage (CTsim). METHODS: The three prostate patients,
      considered to evaluate this hypothesis, had coregistered CT and US scans on
      various days. In particular, two patients had two US-CT datasets each and the
      third one had five US-CT datasets. Deformation fields were computed between pairs
      of US images of the same patient and then applied to the corresponding USsim scan
      to yield a new deformed CTps scan. The original treatment plans were used to
      recalculate dose distributions in the simulation, deformed and ground truth CT
      (CTgt) images to compare dice similarity coefficients, maximum absolute distance,
      and mean absolute distance on CT delineations and gamma index (gamma) evaluations
      on both the Hounsfield units (HUs) and the dose. RESULTS: In the majority,
      deformation did improve the results for all three evaluation methods. The change
      in gamma failure for dose (gammaDose, 3%, 3 mm) ranged from an improvement of
      11.2% in the prostate volume to a deterioration of 1.3% in the prostate and
      bladder. The change in gamma failure for the CT images (gammaCT, 50 HU, 3 mm)
      ranged from an improvement of 20.5% in the anus and rectum to a deterioration of
      3.2% in the prostate. CONCLUSIONS: This new technique may generate CTps images
      that are more representative of the actual patient anatomy than the CTsim scan.

PMID- 27036588
TI  - Calibration of coronary calcium scores determined using iterative image
      reconstruction (AIDR 3D) at 120, 100, and 80 kVp.
AB  - PURPOSE: Computed tomography (CT) radiation dose reduction is frequently achieved
      by applying lower tube voltages and using iterative reconstruction (IR). For
      calcium scoring, the reference protocol at 120 kVp with filtered back projection
      (FBP) is still used, because kVp and IR may influence the Agatston score (AS) and
      volume score (VS). The authors present a two-step method to optimize dose: first,
      to determine the lowest feasible exposure and highest noise thresholds; second,
      to define a calibration method that ensures that the AS and VS are similar to the
      reference protocol. METHODS: AS and VS were measured for an anthropomorphic
      thoracic phantom that includes a calcium calibration module. The phantom was
      scanned on a 320-row CT scanner, at tube voltages of 120 kVp using FBP, and 120,
      100, and 80 kVp using adaptive iterative dose reduction (AIDR 3D) reconstruction.
      The minimum CTDIs were determined based on three objective quality criteria.
      Calibration was performed to estimate adjusted CT number thresholds for the lower
      kVp acquisitions. Finally, the accuracies of the total and individual insert
      scores at dose level close to the minimum CTDI level were investigated and
      compared to low (FBPLD - 120) and high (FBPHD - 120) dose reference protocols
      (based on ten repeated acquisitions for each group). RESULTS: IR allows the
      exposure to be reduced by 69% at 120 kVp, with no significant effect on the total
      scores when averaged over all included dose steps and compared to FBP-120 (AS:
      693 vs 699, p = 0.182; VS: 588 vs 587 mm(3), p = 0.569). Also when averaged over
      ten repeated scans and compared to FBPHD - 120 (AS: 709 vs 704, p = 0.435; VS:
      604 vs 601 mm(3), p = 0.479), there is no statistical significant effect.
      Reducing the peak tube voltage allows even greater dose reductions: 73% at 100
      kVp and 76% at 80 kVp. The calibrated CT number thresholds for analysis at 120,
      100, and 80 kVp were, respectively, 130, 133, and 160 HU for the Agatston score,
      and 130, 132, and 140 HU for the volume score. Following the calibration, the
      mean scores of the four groups with dose variation were not significantly
      different from the reference protocol, at 100 kVp (AS: 698 vs 699, p = 0.818; VS:
      584 vs 587 mm(3), p = 0.365) or at 80 kVp (AS: 698 vs 699, p = 0.996; VS: 586 vs
      587 mm(3), p = 0.827). Similarly, there was no significant score difference with
      FBPLD - 120 during repeated scanning: 100 kVp (AS: 690 vs 694, p = 0.394; VS: 579
      vs 585 mm(3), p = 0.168) and 80 kVp (AS: 703 vs 694, p = 0.115; VS: 588 vs 585
      mm(3), p = 0.613). Compared to FBPHD - 120 group, the relative score deviation
      for the accuracy of the 400 and 800 mg/cm(3) HA inserts with 3 and 5 mm diameter
      is less than 7%. However, the relative deviation of the smaller 1 mm inserts is
      poorer (up to 41% deviations for scores <3). CONCLUSIONS: With iterative
      reconstruction using AIDR 3D, deviations of the total Agatston and volume scores
      remain within 4% of the reference protocol. The 1 mm inserts were detected as
      calcification, but scores less than ten tend to be underestimated. Following the
      calibration process, the application of IR in combination with reduced tube
      voltages allows up to 76% lower radiation dose.

PMID- 27036589
TI  - 3D microwave tomography of the breast using prior anatomical information.
AB  - PURPOSE: The authors have developed a new 3D breast image reconstruction
      technique that utilizes the soft tissue spatial resolution of magnetic resonance
      imaging (MRI) and integrates the dielectric property differentiation from
      microwave imaging to produce a dual modality approach with the goal of augmenting
      the specificity of MR imaging, possibly without the need for nonspecific contrast
      agents. The integration is performed through the application of a soft prior
      regularization which imports segmented geometric meshes generated from MR exams
      and uses it to constrain the microwave tomography algorithm to recover nearly
      uniform property distributions within segmented regions with sharp delineation
      between these internal subzones. METHODS: Previous investigations have
      demonstrated that this approach is effective in 2D simulation and phantom
      experiments and also in clinical exams. The current study extends the algorithm
      to 3D and provides a thorough analysis of the sensitivity and robustness to
      misalignment errors in size and location between the spatial prior information
      and the actual data. RESULTS: Image results in 3D were not strongly dependent on
      reconstruction mesh density, and the changes of less than 30% in recovered
      property values arose from variations of more than 125% in target region size-an
      outcome which was more robust than in 2D. Similarly, changes of less than 13%
      occurred in the 3D image results from variations in target location of nearly 90%
      of the inclusion size. Permittivity and conductivity errors were about 5 times
      and 2 times smaller, respectively, with the 3D spatial prior algorithm in actual
      phantom experiments than those which occurred without priors. CONCLUSIONS: The
      presented study confirms that the incorporation of structural information in the
      form of a soft constraint can considerably improve the accuracy of the property
      estimates in predefined regions of interest. These findings are encouraging and
      establish a strong foundation for using the soft prior technique in clinical
      studies, where their microwave imaging system and MRI can simultaneously collect
      breast exam data in patients.

PMID- 27036590
TI  - Technical Note: Cortical thickness and density estimation from clinical CT using
      a prior thickness-density relationship.
AB  - PURPOSE: Cortical thickness and density are critical components in determining
      the strength of bony structures. Computed tomography (CT) is one possible
      modality for analyzing the cortex in 3D. In this paper, a model-based approach
      for measuring the cortical bone thickness and density from clinical CT images is
      proposed. METHODS: Density variations across the cortex were modeled as a
      function of the cortical thickness and density, location of the cortex, density
      of surrounding tissues, and imaging blur. High resolution micro-CT data of
      cadaver proximal femurs were analyzed to determine a relationship between
      cortical thickness and density. This thickness-density relationship was used as
      prior information to be incorporated in the model to obtain accurate measurements
      of cortical thickness and density from clinical CT volumes. The method was
      validated using micro-CT scans of 23 cadaver proximal femurs. Simulated clinical
      CT images with different voxel sizes were generated from the micro-CT data.
      Cortical thickness and density were estimated from the simulated images using the
      proposed method and compared with measurements obtained using the micro-CT images
      to evaluate the effect of voxel size on the accuracy of the method. Then, 19 of
      the 23 specimens were imaged using a clinical CT scanner. Cortical thickness and
      density were estimated from the clinical CT images using the proposed method and
      compared with the micro-CT measurements. Finally, a case-control study including
      20 patients with osteoporosis and 20 age-matched controls with normal bone
      density was performed to evaluate the proposed method in a clinical context.
      RESULTS: Cortical thickness (density) estimation errors were 0.07 +/- 0.19 mm (
      18 +/- 92 mg/cm(3)) using the simulated clinical CT volumes with the smallest
      voxel size (0.33 * 0.33 * 0.5 mm(3)), and 0.10 +/- 0.24 mm (-10 +/- 115 mg/cm(3))
      using the volumes with the largest voxel size (1.0 * 1.0 * 3.0 mm(3)). A trend
      for the cortical thickness and density estimation errors to increase with voxel
      size was observed and was more pronounced for thin cortices. Using clinical CT
      data for 19 of the 23 samples, mean errors of 0.18 +/- 0.24 mm for the cortical
      thickness and 15 +/- 106 mg/cm(3) for the density were found. The case-control
      study showed that osteoporotic patients had a thinner cortex and a lower cortical
      density, with average differences of -0.8 mm and -58.6 mg/cm(3) at the proximal
      femur in comparison with age-matched controls (p-value < 0.001). CONCLUSIONS:
      This method might be a promising approach for the quantification of cortical bone
      thickness and density using clinical routine imaging techniques. Future work will
      concentrate on investigating how this approach can improve the estimation of
      mechanical strength of bony structures, the prevention of fracture, and the
      management of osteoporosis.

PMID- 27036591
TI  - A general model for stray dose calculation of static and intensity-modulated
      photon radiation.
AB  - PURPOSE: There is an increasing number of cancer survivors who are at risk of
      developing late effects caused by ionizing radiation such as induction of second
      tumors. Hence, the determination of out-of-field dose for a particular treatment
      plan in the patient's anatomy is of great importance. The purpose of this study
      was to analytically model the stray dose according to its three major components.
      METHODS: For patient scatter, a mechanistic model was developed. For collimator
      scatter and head leakage, an empirical approach was used. The models utilize a
      nominal beam energy of 6 MeV to describe two linear accelerator types of a single
      vendor. The parameters of the models were adjusted using ionization chamber
      measurements registering total absorbed dose in simple geometries. Whole-body
      dose measurements using thermoluminescent dosimeters in an anthropomorphic
      phantom for static and intensity-modulated treatment plans were compared to the
      3D out-of-field dose distributions calculated by a combined model. RESULTS: The
      absolute mean difference between the whole-body predicted and the measured out-of
      field dose of four different plans was 11% with a maximum difference below 44%.
      Computation time of 36 000 dose points for one field was around 30 s. By
      combining the model-calculated stray dose with the treatment planning system
      dose, the whole-body dose distribution can be viewed in the treatment planning
      system. CONCLUSIONS: The results suggest that the model is accurate, fast and can
      be used for a wide range of treatment modalities to calculate the whole-body dose
      distribution for clinical analysis. For similar energy spectra, the mechanistic
      patient scatter model can be used independently of treatment machine or beam
      orientation.

PMID- 27036592
TI  - Split Bregman multicoil accelerated reconstruction technique: A new framework for
      rapid reconstruction of cardiac perfusion MRI.
AB  - PURPOSE: Rapid reconstruction of undersampled multicoil MRI data with iterative
      constrained reconstruction method is a challenge. The authors sought to develop a
      new substitution based variable splitting algorithm for faster reconstruction of
      multicoil cardiac perfusion MRI data. METHODS: The new method, split Bregman
      multicoil accelerated reconstruction technique (SMART), uses a combination of
      split Bregman based variable splitting and iterative reweighting techniques to
      achieve fast convergence. Total variation constraints are used along the spatial
      and temporal dimensions. The method is tested on nine ECG-gated dog perfusion
      datasets, acquired with a 30-ray golden ratio radial sampling pattern and ten
      ungated human perfusion datasets, acquired with a 24-ray golden ratio radial
      sampling pattern. Image quality and reconstruction speed are evaluated and
      compared to a gradient descent (GD) implementation and to multicoil k-t SLR, a
      reconstruction technique that uses a combination of sparsity and low rank
      constraints. RESULTS: Comparisons based on blur metric and visual inspection
      showed that SMART images had lower blur and better texture as compared to the GD
      implementation. On average, the GD based images had an ~18% higher blur metric as
      compared to SMART images. Reconstruction of dynamic contrast enhanced (DCE)
      cardiac perfusion images using the SMART method was ~6 times faster than standard
      gradient descent methods. k-t SLR and SMART produced images with comparable image
      quality, though SMART was ~6.8 times faster than k-t SLR. CONCLUSIONS: The SMART
      method is a promising approach to reconstruct good quality multicoil images from
      undersampled DCE cardiac perfusion data rapidly.

PMID- 27036593
TI  - IMRT QA: Selecting gamma criteria based on error detection sensitivity.
AB  - PURPOSE: The gamma comparison is widely used to evaluate the agreement between
      measurements and treatment planning system calculations in patient-specific
      intensity modulated radiation therapy (IMRT) quality assurance (QA). However,
      recent publications have raised concerns about the lack of sensitivity when
      employing commonly used gamma criteria. Understanding the actual sensitivity of a
      wide range of different gamma criteria may allow the definition of more
      meaningful gamma criteria and tolerance limits in IMRT QA. We present a method
      that allows the quantitative determination of gamma criteria sensitivity to
      induced errors which can be applied to any unique combination of device, delivery
      technique, and software utilized in a specific clinic. METHODS: A total of 21
      DMLC IMRT QA measurements (ArcCHECK(r), Sun Nuclear) were compared to QA plan
      calculations with induced errors. Three scenarios were studied: MU errors, multi
      leaf collimator (MLC) errors, and the sensitivity of the gamma comparison to
      changes in penumbra width. Gamma comparisons were performed between measurements
      and error-induced calculations using a wide range of gamma criteria, resulting in
      a total of over 20 000 gamma comparisons. Gamma passing rates for each error
      class and case were graphed against error magnitude to create error curves in
      order to represent the range of missed errors in routine IMRT QA using 36
      different gamma criteria. RESULTS: This study demonstrates that systematic errors
      and case-specific errors can be detected by the error curve analysis. Depending
      on the location of the error curve peak (e.g., not centered about zero), 3%/3 mm
      threshold = 10% at 90% pixels passing may miss errors as large as 15% MU errors
      and +/-1 cm random MLC errors for some cases. As the dose threshold parameter was
      increased for a given %Diff/distance-to-agreement (DTA) setting, error
      sensitivity was increased by up to a factor of two for select cases. This
      increased sensitivity with increasing dose threshold was consistent across all
      studied combinations of %Diff/DTA. Criteria such as 2%/3 mm and 3%/2 mm with a
      50% threshold at 90% pixels passing are shown to be more appropriately sensitive
      without being overly strict. However, a broadening of the penumbra by as much as
      5 mm in the beam configuration was difficult to detect with commonly used
      criteria, as well as with the previously mentioned criteria utilizing a threshold
      of 50%. CONCLUSIONS: We have introduced the error curve method, an analysis
      technique which allows the quantitative determination of gamma criteria
      sensitivity to induced errors. The application of the error curve method using
      DMLC IMRT plans measured on the ArcCHECK(r) device demonstrated that large errors
      can potentially be missed in IMRT QA with commonly used gamma criteria (e.g.,
      3%/3 mm, threshold = 10%, 90% pixels passing). Additionally, increasing the dose
      threshold value can offer dramatic increases in error sensitivity. This approach
      may allow the selection of more meaningful gamma criteria for IMRT QA and is
      straightforward to apply to other combinations of devices and treatment
      techniques.

PMID- 27036594
TI  - Helium ions for radiotherapy? Physical and biological verifications of a novel
      treatment modality.
AB  - PURPOSE: Modern facilities for actively scanned ion beam radiotherapy allow in
      principle the use of helium beams, which could present specific advantages,
      especially for pediatric tumors. In order to assess the potential use of these
      beams for radiotherapy, i.e., to create realistic treatment plans, the authors
      set up a dedicated (4)He beam model, providing base data for their treatment
      planning system TRiP98, and they have reported that in this work together with
      its physical and biological validations. METHODS: A semiempirical beam model for
      the physical depth dose deposition and the production of nuclear fragments was
      developed and introduced in TRiP98. For the biological effect calculations the
      last version of the local effect model was used. The model predictions were
      experimentally verified at the HIT facility. The primary beam attenuation and the
      characteristics of secondary charged particles at various depth in water were
      investigated using (4)He ion beams of 200 MeV/u. The nuclear charge of secondary
      fragments was identified using a DeltaE/E telescope. 3D absorbed dose
      distributions were measured with pin point ionization chambers and the biological
      dosimetry experiments were realized irradiating a Chinese hamster ovary cells
      stack arranged in an extended target. RESULTS: The few experimental data
      available on basic physical processes are reproduced by their beam model. The
      experimental verification of absorbed dose distributions in extended target
      volumes yields an overall agreement, with a slight underestimation of the lateral
      spread. Cell survival along a 4 cm extended target is reproduced with remarkable
      accuracy. CONCLUSIONS: The authors presented a simple simulation model for
      therapeutical (4)He beams which they introduced in TRiP98, and which is validated
      experimentally by means of physical and biological dosimetries. Thus, it is now
      possible to perform detailed treatment planning studies with (4)He beams, either
      exclusively or in combination with other ion modalities.

PMID- 27036595
TI  - Comment on "Comparison and uncertainty evaluation of different calibration
      protocols and ionization chambers for low-energy surface brachytherapy dosimetry"
      [Med. Phys. 42, 4954-4964 (2015)].

PMID- 27036596
TI  - Response to "Comment on 'Comparison and uncertainty evaluation of different
      calibration protocols and ionization chambers for low-energy surface
      brachytherapy dosimetry' " [Med. Phys. 42, 4954-4964 (2015)].

PMID- 27036597
TI  - Responses of soil microbial biomass and bacterial community structure to closed
      off management (an ecological natural restoration measures): A case study of
      Dongting Lake wetland, middle China.
AB  - Soil microbial biomass (SMB) and bacterial community structure, which are
      critical to global ecosystem and fundamental ecological processes, are sensitive
      to anthropogenic activities and environmental conditions. In this study, we
      examined the possible effects of closed-off management (an ecological natural
      restoration measures, ban on anthropogenic activity, widely employed for many
      important wetlands) on SMB, soil bacterial community structure and functional
      marker genes of nitrogen cycling in Dongting Lake wetland. Soil samples were
      collected from management area (MA) and contrast area (CA: human activities, such
      as hunting, fishing and draining, are permitted) in November 2013 and April 2014.
      Soil properties, microbial biomass carbon (MBC), and bacterial community
      structure were investigated. Comparison of the values of MA and CA showed that
      SMB and bacterial community diversity of the MA had a significant increase after
      7 years closed-off management. The mean value of Shannon-Weiner diversity index
      of MA and CA respectively were 2.85 and 2.07. The gene copy numbers of 16S rRNA
      and nosZ of MA were significant higher than those of CA. the gene copy numbers of
      ammonia-oxidizing archaea (AOA) and nirK of MA were significant lower than those
      of CA. However, there was no significant change in the gene copy numbers of
      ammonia-oxidizing bacteria (AOB) and nirS. 

PMID- 27036598
TI  - Correcting Quasimodo in the 21st century: Advances in the care for major spine
      surgery.

PMID- 27036599
TI  - Surgical considerations for major deformity correction spine surgery.
AB  - Spinal deformity is defined as abnormality in alignment, formation, or curvature
      of one or more segments of the spine. Its characteristic clinical presentation
      and radiographic appearance differ according to patient age and the underlying
      cause. The most common deformity in the pediatric population is adolescent
      idiopathic scoliosis, whereas in adults many patients present with de novo
      deformity secondary to degenerative disease. Although the specific goals differ
      between patients, the broad aims include restoration of regional and global
      alignment, decompression of neural elements as necessary, and establishment of a
      solid fusion. Surgeons perform deformity correction by various approaches and
      techniques to achieve the desired correction while minimizing perioperative risk.

PMID- 27036600
TI  - Airway management for cervical spine surgery.
AB  - Cervical spine surgery is one of the most commonly performed spine surgeries in
      the United States, and 90% of the cases are related to degenerative cervical
      spine disease (the rest to cervical spine trauma and/or instability). The airway
      management for cervical spine surgery represents a crucial step in the anesthetic
      management to avoid injury to the cervical cord. The crux for upper airway
      management for cervical spine surgery is maintaining the neck in a neutral
      position with minimal neck movement during endotracheal intubation. Therefore,
      the conventional direct laryngoscopy (DL) can be unsuitable for securing the
      upper airway in cervical spine surgery, especially in cases of cervical spine
      instability and myelopathy. This review discusses the most recent evidence-based
      facts of the main advantages and limitations of different techniques available
      for upper airway management for cervical spine surgery. 

PMID- 27036601
TI  - Acute spinal cord injury.
AB  - Acute spinal cord injury (SCI) is a devastating event with high mortality and,
      among survivors, a high degree of morbidity due to both motor and sensory
      deficits. The damage that occurs with a SCI is recognized to be
      pathophysiologically biphasic: the initial insult to neural tissue can be
      followed by a secondary process of progressive ischemia that may worsen the
      severity of dysfunction. The extent of this secondary insult is potentially
      modifiable, and a variety of interventions have been studied in an attempt to
      improve motor and sensory outcomes. What follows is a brief review of some such
      procedural and pharmacologic interventions, including early decompressive
      surgery, use of methylprednisolone, and blood pressure and respiratory
      management, which have been proposed to improve outcomes after SCI. 

PMID- 27036602
TI  - Perioperative blood conservation strategies for major spine surgery.
AB  - BACKGROUND: Orthopedic surgery, especially spine and spinal deformity surgery,
      may be associated with high perioperative blood loss. In order to reduce the risk
      of excessive blood loss and unnecessary blood transfusions, strategies such as
      Patient Blood Management including goal-directed coagulation management have been
      developed. RECENT FINDINGS: Adverse effects of allogeneic blood transfusions have
      been shown for most surgical fields including orthopedic surgery. Several efforts
      have been made to increase the preoperative red blood cell (RBC) mass, to reduce
      the intraoperative blood loss, and to use restrictive transfusion triggers in
      order to minimize or avoid RBC transfusions. Measures to reduce intraoperative
      blood loss include new surgical techniques, use of cell salvage where possible,
      bedside coagulation management with point-of-care devices, substitution of
      coagulation factors, antifibrinolytic agents, and desmopressin, induced
      hypotension, and avoidance of hypothermia. SUMMARY: Blood conservation in spinal
      surgery is a multidisciplinary approach and the efficacy of most single measures
      has been shown. Cost-effectiveness and the benefits of long-term patient outcomes
      are the subjects of current and future research.

PMID- 27036603
TI  - Neurophysiological monitoring and spinal cord integrity.
AB  - An integral part of a major spine surgery is the intraoperative
      neurophysiological monitoring (IONM). By providing continuous functional
      assessment of specific anatomic structures, IONM allows the rapid detection of
      neuronal compromise and the opportunity for corrective action before an insult
      causes permanent neurological damage. Thus, IONM functions not just as a
      diagnostic tool but may also improve surgical outcomes. Effective clinical
      application requires a thorough understanding of the scope and limitations of
      IONM modalities not only by the monitoring team but also by the surgeon and
      anesthesiologist. Intraoperatively, collaboration and communication between
      monitorist, surgeon, and anesthesiologist are critical to the effectiveness of
      IONM. In this study, we review specific monitoring modalities, focusing on the
      relevant anatomy, physiology, and mechanisms of neuronal injury during major
      spine surgery. We discuss how these factors interact with anesthetic and surgical
      management. This review concludes with the current controversies surrounding the
      evidence in support of IONM and directions of future research. 

PMID- 27036604
TI  - Perioperative visual loss.
AB  - Perioperative visual loss is an infrequent, devastating complication associated
      with spine surgery, most commonly from ischemic optic neuropathy. Current
      research and expert opinion indicate that it is associated with procedures that
      create elevated venous pressure in the head for prolonged periods of time. The
      largest case-control study on ischemic optic neuropathy associated with spine
      surgery found six independent and significant risk factors including male sex,
      obesity, Wilson frame use, longer operative times, greater blood loss, and a
      lower colloid to crystalloid ratio in the non-blood fluid administration. The
      American Society of Anesthesiologists developed a practice advisory for the
      prevention of this complication. In this setting, it is advisable to avoid
      significant physiologic and hemodynamic perturbations as much as possible, given
      the uncertainty of the pathophysiology. Because prevention of this complication
      cannot be guaranteed, consent for perioperative visual loss should be strongly
      considered in patients at high risk for this complication. 

PMID- 27036605
TI  - Non-opioid analgesics: Novel approaches to perioperative analgesia for major
      spine surgery.
AB  - Perioperative pain management is a significant challenge following major spine
      surgery. Many pathways contribute to perioperative pain, including nociceptive,
      inflammatory, and neuropathic sources. Although opioids have long been a mainstay
      for perioperative analgesia, other non-opioid therapies have been increasingly
      used as part of a multimodal analgesic regimen to provide improved pain control
      while minimizing opioid-related side effects. Here we review the evidence
      supporting the use of novel analgesic approaches as an alternative to intravenous
      opioids for major spine surgery. 

PMID- 27036606
TI  - Enhanced recovery after surgery (ERAS) and its applicability for major spine
      surgery.
AB  - This article examines the relevance of applying the Enhanced Recovery after
      Surgery (ERAS) approach to patients undergoing major spinal surgery. The history
      of ERAS, details of the components of the approach and the underlying rationale
      are explained. Evidence on outcomes achieved by using the ERAS approach in other
      orthopaedic and complex surgical procedures is then outlined. Data on major
      spinal surgery rates and current practice are reviewed; the rationale for using
      ERAS in major spinal surgery is discussed, and potential challenges to its
      adoption are acknowledged. A thorough literature search is then undertaken to
      examine the use of ERAS pathways in major spinal surgery, and the results are
      presented. The article then reviews the evidence to support the application of
      individual ERAS components such as patient education, multimodal pain management,
      surgical approach, blood loss, nutrition and physiotherapy in major spinal
      surgery, and discusses the need for further robust research to be undertaken. The
      article concludes that given the rising costs of surgery and levels of patient
      dissatisfaction, an ERAS pathway that focuses on optimising clinical procedures
      by adopting evidence-based practice and improving logistics should enable major
      spinal surgery patients to recover more quickly with lower rates of morbidity and
      improved longer-term outcomes. 

PMID- 27036607
TI  - Postoperative complications of spine surgery.
AB  - A variety of surgical approaches are available for the treatment of spine
      diseases. Complications can arise intraoperatively, in the immediate
      postoperative period, or in a delayed fashion. These complications may lead to
      severe or even permanent morbidity if left unrecognized and untreated [1-4]. Here
      we review a range of complications in the early postoperative period from more
      benign complications such as postoperative nausea and vomiting (PONV) to more
      feared complications leading to permanent loss of neurological function or death
      [5]. Perioperative pain management is covered in a separate review (Chapter 8). 

PMID- 27036608
TI  - Erratum to "Post-operative pulmonary complications: Understanding definitions and
      risk assessment" [Best Pract Res Clin Anaesthesiol 29 (2015) 315-330].

PMID- 27036609
TI  - Prevalence, awareness, treatment, control and risk factors related to
      hypertension among urban adults in Inner Mongolia 2014: differences between
      Mongolian and Han populations.
AB  - BACKGROUND: Han and Mongolian populations constitute approximately 96% of the
      population of Inner Mongolia Autonomous Region, and the two ethnic groups have
      different genetic backgrounds and lifestyle. We aim to assess the prevalence,
      awareness, treatment, control, and related risk factors of hypertension among
      urban adults in Inner Mongolia, with the comparison of the differences between
      Mongolian and Han populations in this respect. METHODS: Three thousand two
      hundred fifty-one individuals aged 20-80 years (2326 Han and 925 Mongolian) were
      selected using a multistage cluster sampling method from Inner Mongolia in 2014.
      The adjusted prevalence, awareness, treatment and control of hypertension were
      evaluated by the Logistic regression. In addition, possible interactions were
      also tested. When interactions were found significant, strata-specific analysis
      were performed. Multivariate logistic regression was used for estimating
      independent associations between risk factors and hypertension. RESULTS: The
      prevalence of hypertension was 27.47% for Han population, 31.46% for Mongolian
      population. The adjusted prevalence, awareness, treatment and control of
      hypertension were 26.45, 65.43, 78.24 and 48.28% in Han, and 31.30, 68.22, 85.57
      and 50.55% in Mongolian, respectively. There was no significant difference in the
      adjusted awareness, treatment and control of hypertension among Mongolian and Han
      adult residents (all P >0.05). Lower prevalence of hypertension was associated
      with younger age and healthy weight in both Mongolian and Han adults. Within Han
      adults, high education, moderate physical activity and non-alcohol drinkers were
      additionally associated with lower prevalence of hypertension, whereas within
      Mongolian adults, lower prevalence was associated with being female. Among
      residents with medium education level, nondrinkers had 0.60 times lower odds of
      having hypertension than current drinkers (OR = 0.60, 95% CI: 0.44-0.82); among
      residents with high education level, nondrinkers has 0.65 times lower odds of
      having hypertension than current drinkers (OR = 0.65, 95% CI: 0.43-0.97).
      CONCLUSIONS: Mongolian population had a higher prevalence of hypertension than
      Han population. There were no significant difference between Mongolian and Han
      population in awareness, treatment and control of hypertension, which suggested
      that there was no difference between the two ethnicities in the distribution of
      health resources.

PMID- 27036610
TI  - Serum saturated fatty acid decreases plasma adiponectin and increases leptin
      throughout pregnancy independently of BMI.
AB  - OBJECTIVE: The aim of this study was to investigate whether serum concentrations
      of total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), and
      their fractions are associated with plasma adiponectin and leptin concentrations
      throughout pregnancy. METHODS: A prospective cohort of 201 pregnant women was
      followed from gestational weeks 5 to 13, 20 to 26, and 30 to 36. Blood samples
      were collected at the three visits after 12 h of fasting. Fatty acid
      concentrations were determined using fast gas-liquid chromatography. Plasma
      adiponectin (MUg/mL) and leptin (ng/dL) concentrations were evaluated using
      enzyme-linked immunosorbent assay kits. Statistical analyses included median
      adipokine concentrations according to the tertiles of fatty acid distribution and
      multiple linear mixed-effect models adjusted for body mass index, gestational
      age, total energy intake, alcohol consumption, and smoking. RESULTS: Women
      classified in the third SFA concentration tertile had lower median values of
      adiponectin compared with those in the first tertile ([first trimester: first
      tertile = 5.36; third tertile = 5.00]; [second trimester: first tertile = 6.39;
      third tertile = 4.47]; [third trimester: first tertile = 6.46; third tertile =
      4.60]). Similar trends were observed for the 14:0, 16:0 and 18:0 fractions. In
      the multiple longitudinal models, total SFA (beta = -41.039; P = 0.008) and 16:0
      were negatively associated with plasma adiponectin (16:0, beta = -0.511; P =
      0.001). Total PUFA omega-6 (beta = 28.961; P = 0.002) and 18:2 omega-6 (beta =
      0.259, P = 0.006) were positively associated with the adiponectin. Total SFA
      (beta = 0.110, P = 0.007), 14:0 (beta = 0.072, P = 0.011), and 20:3 omega-6 (beta
      = 0.039; P = 0.035) were positively associated with plasma leptin. CONCLUSIONS:
      Total serum SFA and the 16:0 fraction were negatively associated with plasma
      adiponectin and positively associated with leptin concentrations. Total omega-6
      PUFA was positively associated only with plasma adiponectin concentrations
      throughout pregnancy.

PMID- 27036611
TI  - Phytopharmacologic preparations as predictors of plant bioactivity: A particular
      approach to Echinacea purpurea (L.) Moench antioxidant properties.
AB  - OBJECTIVE: A large body of evidence has confirmed a multitude of health benefits
      of plant products and their derived formulations. Echinacea purpurea (L.) Moench
      is a good example, widely used due to its therapeutic properties. In the present
      study, the chemical composition of the different samples and antioxidant
      properties of E. purpurea hydroethanolic and aqueous extracts obtained from dry
      or fresh raw material were evaluated and compared with dietary supplements based
      on the same plant (tablets and syrup), to determine the most active
      phytopharmacologic preparation or formulation. METHODS: Chemical composition of
      the different samples was assessed through the determination of free sugars,
      organic acids and tocopherols. The in vitro antioxidant properties were
      determined using four assays: 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals
      scavenging activity, reducing power, inhibition of b-carotene bleaching and
      inhibition of lipid peroxidation by thiobarbituric acid reactive substances
      (TBARS) assay. Total phenolics and flavonoids were also determined. RESULTS:
      Overall, the hydroethanolic extract of fresh plant revealed the highest activity,
      directly related with its higher contents in phenolic (229.22 +/- 4.38 mg gallic
      acid equivalent [GAE]/mL), flavonoids (124.83 +/- 7.47 mg GAE/mL), organic acids
      (8.89 +/- 0.10 g/100 g), and tocopherols (4.55 +/- 0.02 mg/100 g). Tablets
      followed by syrup revealed the worst effect, positively correlated with the
      lowest abundance in bioactive molecules. The weak in vitro antioxidant potential
      of commercial phytopharmacologic formulations could be related to their chemical
      composition, including the addition of excipients. CONCLUSION: Further studies
      are necessary to deepen knowledge on this area, namely focusing on in vivo
      experiments, to establish upcoming guidelines to improve the quality and
      bioavailability of phytopharmacologic formulations.

PMID- 27036612
TI  - The linear relationship between systolic pulmonary artery pressure and mean
      pulmonary artery pressure is maintained regardless of autonomic or rhythm
      disturbances.
AB  - BACKGROUND: In the pulmonary circulation, there is a linear relationship between
      systolic pulmonary arterial pressure (SPAP) and mean pulmonary arterial pressure
      (MPAP). The aim of this study was to determine the passive or active nature of
      this mechanism by exploring the relationship in patients with and without
      autonomic rhythm control of the heart and pulmonary circulation. METHODS:
      Pulmonary arterial pressure recordings from non-transplanted patients and
      patients with heart transplants or double lung transplants were retrospectively
      reviewed. The relationships between systolic, diastolic, and mean pulmonary
      arterial pressures were explored. RESULTS: A linear relationship was observed
      between the SPAP and MPAP, whether patients were paced (MPAP = 0.56 SPAP + 3.86
      mmHg, r (2)  = 0.889), treated with inotropes (MPAP = 0.55 SPAP + 5.52 mmHg, r
      (2)  = 0.947) or pulmonary vasodilators (MPAP = 0.58 SPAP + 2.41 mmHg, r (2)  =
      0.927), were exercising (MPAP = 0.61 SPAP + 1.18 mmHg, r (2)  = 0.967), had a
      heart transplant (MPAP = 0.66 SPAP +0.87 mmHg, r (2)  = 0.849), a double lung
      transplant (MPAP = 0.7 SPAP +0.48 mmHg, r (2)  = 0.915), or no intervention (MPAP
      = 0.59 SPAP +1.75 mmHg, r (2)  = 0.937). CONCLUSION: We demonstrate that the
      linear relationship between SPAP and MPAP remains in several situations.
      Therefore, we conclude that the underlying mechanism is a passive consequence of
      the elastic properties of the cardiopulmonary unit.

PMID- 27036613
TI  - Prevalence and impact of urinary incontinence in men with chronic obstructive
      pulmonary disease: a questionnaire survey.
AB  - OBJECTIVES: To identify urinary incontinence and its impact on men with stable
      chronic obstructive pulmonary disease (COPD) and men without lung disease.
      DESIGN: Prospective questionnaire study. SETTING: Outpatients attending a public
      metropolitan hospital. PARTICIPANTS: Men with COPD (n=49) and age-matched men
      without lung disease (n=36). INTERVENTIONS: Validated questionnaires to identify
      the prevalence and impact of urinary incontinence. MAIN OUTCOME MEASURES:
      Prevalence of urinary incontinence and relationship with disease-specific
      factors, and relationship of urinary incontinence with anxiety and depression.
      RESULTS: The prevalence of urinary incontinence was higher in men with COPD
      (n=19/49) compared with men without lung disease (n=6/36; P=0.027). In men with
      COPD, symptoms of urgency were more prevalent in men with urinary incontinence
      (P=0.005), but this was not evident in men without lung disease (P=0.101). Only
      men with COPD reported symptoms of urgency associated with dyspnoea, and this did
      not vary between men with and without urinary incontinence (P=0.138). In men with
      COPD, forced expiratory volume in 1 second (FEV1) was lower in those with urinary
      incontinence compared with those without urinary incontinence {mean 38 [standard
      deviation (SD) 14] % predicted vs 61 (SD 24) % predicted; P=0.002}. The impact of
      urinary incontinence did not differ between the two groups (P=0.333).
      CONCLUSIONS: Incontinence is more prevalent in men with COPD than in men without
      lung disease. The prevalence of urinary incontinence increases with greater
      disease severity, as reflected by lower FEV1. Screening for urinary incontinence
      should be considered in men with COPD and compromised lung function.

PMID- 27036614
TI  - [Bilateral stellate neuroretinitis secondary to renal artery stenosis].

PMID- 27036615
TI  - [An unusual CRAO].

PMID- 27036616
TI  - [Viscodissection of dua's layer after partial big bubble].

PMID- 27036617
TI  - A high-throughput screening-compatible homogeneous time-resolved fluorescence
      assay measuring the glycohydrolase activity of human poly(ADP-ribose)
      glycohydrolase.
AB  - Poly(ADP-ribose) (PAR) polymers are transient post-translational modifications,
      and their formation is catalyzed by poly(ADP-ribose) polymerase (PARP) enzymes. A
      number of PARP inhibitors are in advanced clinical development for BRCA-mutated
      breast cancer, and olaparib has recently been approved for BRCA-mutant ovarian
      cancer; however, there has already been evidence of developed resistance
      mechanisms. Poly(ADP-ribose) glycohydrolase (PARG) catalyzes the hydrolysis of
      the endo- and exo-glycosidic bonds within the PAR polymers. As an alternative
      strategy, PARG is a potentially attractive therapeutic target. There is only one
      PARG gene, compared with 17 known PARP family members, and therefore a PARG
      inhibitor may have wider application with fewer compensatory mechanisms. Prior to
      the initiation of this project, there were no known existing cell-permeable small
      molecule PARG inhibitors for use as tool compounds to assess these hypotheses and
      no suitable high-throughput screening (HTS)-compatible biochemical assays
      available to identify start points for a drug discovery project. The development
      of this newly described high-throughput homogeneous time-resolved fluorescence
      (HTRF) assay has allowed HTS to proceed and, from this, the identification and
      advancement of multiple validated series of tool compounds for PARG inhibition.

PMID- 27036618
TI  - Single-step method for beta-galactosidase assays in Escherichia coli using a 96
      well microplate reader.
AB  - Historically, the lacZ gene is one of the most universally used reporters of gene
      expression in molecular biology. Its activity can be quantified using an
      artificial substrate, o-nitrophenyl-beta-d-galactopyranoside (ONPG). However, the
      traditional method for measuring LacZ activity (first described by J. H. Miller
      in 1972) can be challenging for a large number of samples, is prone to
      variability, and involves hazardous compounds for lysis (e.g., chloroform,
      toluene). Here we describe a single-step assay using a 96-well microplate reader
      with a proven alternative cell permeabilization method. This modified protocol
      reduces handling time by 90%.

PMID- 27036619
TI  - Memories of good deeds past: The reinforcing power of prosocial behavior in
      children.
AB  - Does considering one's past prosociality affect future behavior? Prior research
      has revealed instances in which adults engage in additional prosocial behavior
      moral reinforcement-as well as instances in which adults engage in worse behavior
      moral licensing. The current study examined the developmental origins of these
      effects by testing whether 6- to 8-year-old children (N=225) are more or less
      generous after recalling their own good deeds. Children were asked to recount a
      time when they were nice, were mean, or watched a movie. Children behaved more
      generously after recalling a time when they were nice. We show that this boost in
      generosity was not simply the result of instructing children to consider nice
      behavior; children's giving did not increase after recalling others' good deeds.
      We also show that, even after recounting multiple instances of their past
      goodness, children continue to behave more generously. These findings suggest
      that doing good leads to more good in children.

PMID- 27036620
TI  - Packed red blood cell transfusion after surgery: are we "overtranfusing" our
      patients?
AB  - BACKGROUND: Data on the hemoglobin (Hb) after transfusion, or the "target," which
      reflects the "dose" of blood given are not well studied. We sought to examine the
      incidence and causes of "over transfusion" of red blood cells after surgery.
      METHODS: Data on blood utilization including Hb triggers and targets were
      obtained for patients undergoing colorectal, pancreas, or liver surgery between
      2010 and 2013. RESULTS: A total of 2,905 patients were identified, of which 895
      (31%) were transfused (median age 64, interquartile range: 53 to 72; 51% men;
      median American Society of Anesthesiologists class 3, interquartile range: 3-3;
      51% pancreatic, 14% hepatobiliary, 21% colorectal, and 14% other). Among these,
      512 (57%) were overtransfused (final Hb target after transfusion >=9.0 g/dL).
      Among patients who were overtransfused, 171 (33%) were transfused at too high an
      initial trigger (>8.0 g/dL), whereas 304 (59%) had an appropriate trigger but
      received >=2 packed red blood cell (PRBC) units, suggesting an opportunity to
      have transfused fewer units. There was significant variation in overtransfusion
      among surgeons (range 0% to 80%, P = .003). CONCLUSIONS: Excess use of blood
      transfusion is common and was due to PRBC utilization for too high a transfusion
      trigger, as well as too many units transfused.

PMID- 27036621
TI  - Longitudinal analysis of cytokine expression during neoadjuvant chemoradiotherapy
      and subsequent surgery in esophageal cancer patients.
AB  - BACKGROUND: The purpose of this study was to provide more insight in the course
      of cytokine concentrations related to pathologic response (pR) and complications
      after neoadjuvant chemoradiotherapy (NCRT) and esophagectomy in esophageal cancer
      patients. METHODS: Patients treated with NCRT followed by transthoracic
      esophagectomy (n = 35) or transthoracic esophagectomy alone (n = 8) were
      included. Eight different cytokine concentrations were determined during NCRT,
      esophagectomy, and the first postoperative week. RESULTS: Platelet-activating
      factor before NCRT was associated with pR (P = .011) and remained elevated in
      patients with a better response. Concentrations of intestinal fatty acid-binding
      protein and angiopoietin 1 (Ang-1) were different between patients with and
      without NCRT. Decreased concentrations of Ang-1 on the third postoperative day
      were associated with postoperative complications (P = .046). CONCLUSIONS: In this
      observational study, elevated platelet-activating factor concentrations before
      NCRT were associated with pR. NCRT is associated with decreased Ang-1
      concentrations, whereas reduced Ang-1 concentrations were associated with
      postoperative complications.

PMID- 27036623
TI  - EAGER: efficient ancient genome reconstruction.
AB  - BACKGROUND: The automated reconstruction of genome sequences in ancient genome
      analysis is a multifaceted process. RESULTS: Here we introduce EAGER, a time
      efficient pipeline, which greatly simplifies the analysis of large-scale genomic
      data sets. EAGER provides features to preprocess, map, authenticate, and assess
      the quality of ancient DNA samples. Additionally, EAGER comprises tools to
      genotype samples to discover, filter, and analyze variants. CONCLUSIONS: EAGER
      encompasses both state-of-the-art tools for each step as well as new
      complementary tools tailored for ancient DNA data within a single integrated
      solution in an easily accessible format.

PMID- 27036622
TI  - Molecular alterations in the TCR signaling pathway in patients with aplastic
      anemia.
AB  - BACKGROUND: A previous study has demonstrated a significantly increased CD3zeta
      gene expression level in aplastic anemia (AA). However, the mechanism underlying
      the upregulated CD3zeta mRNA expression level and that of T cell activation
      signaling molecules in AA patients remains unclear. Thus, we investigated the
      expression levels of the CD3zeta, CD28, CTLA-4, and Cbl-b genes, the SNP rs231775
      in the CTLA-4 gene, and the distribution of the CD3zeta 3'-UTR splice variant in
      AA patients. METHODS: CD3zeta 3'-UTR splice variants were identified in
      peripheral blood mononuclear cells (PBMCs) from 48 healthy individuals and 67
      patients with AA [37 cases of severe aplastic anemia (SAA) and 30 cases of non
      sever aplastic anemia (NSAA)] by RT-PCR. CD3zeta, CD28, CTLA-4, and Cbl-b gene
      expression was analyzed by real-time quantitative PCR. The SNP rs231775 in CTLA-4
      gene was analyzed by PCR-RFLP. RESULTS: CD3zeta and CD28 expression was
      significantly higher, while CTLA-4 and Cbl-b expression was significantly lower
      in AA patients compared with healthy individuals. Significantly higher CD3zeta
      expression was found in the NSAA subgroup compared with the SAA subgroup. 64 % of
      the AA samples had the same genotype (WT(+)AS(+)CD3zeta 3'-UTR); 22 % of the AA
      patients had a WT(+)AS(-)CD3zeta 3'-UTR genotype, and 14 % of the AA patients had
      a WT(-)AS(+)CD3zeta 3'-UTR genotype. The CD3zeta expression level of WT(-)AS(+)
      subgroup was the highest in the SAA patients. A significantly higher frequency of
      the GG genotype (mutant type, homozygous) of SNP rs231775 in CTLA-4 gene was
      found in the AA patients. Positive correlation between the CTLA-4 and Cbl-b gene
      expression levels was found in healthy individuals with the AA and AG genotypes,
      but not in the AA patients. CONCLUSIONS: This is the first study analyzing the
      expression characteristics of the CD28, CTLA-4, and Cbl-b genes in AA. Our
      results suggest that aberrant T cell activation may be related to the first and
      second signals of T cell activation in AA. The GG genotype of SNP rs231775 in
      CTLA-4 gene might be associated with AA risk in the Chinese population. The
      characteristics of CD3zeta 3'-UTR alternative splicing may be an index for
      evaluating the T cell activation status in AA patients, particularly in SAA
      patients.

PMID- 27036624
TI  - A honeycomb-like structure in the left anterior descending coronary artery
      treated using a scoring device and drug-eluting stent implantation: a case
      report.
AB  - BACKGROUND: A honeycomb-like structure in the coronary artery is rarely diagnosed
      by intracoronary ultrasound or optical coherence tomography. Further, its
      structural mechanisms and response to interventional therapy remain unknown. CASE
      PRESENTATION: A 59-year-old Japanese man was referred to our hospital because of
      acute decompensated heart failure with rapid atrial fibrillation. After receiving
      anticoagulant therapy, a coronary angiogram revealed a braid-like appearance and
      an intracoronary ultrasound image confirmed a honeycomb-like structure in the mid
      left anterior descending coronary artery. We inserted two guide wires into
      different partitions. Although a balloon angioplasty with a scoring device could
      not completely fenestrate these partitions, a stent implant was able to
      completely compress the structure easily. CONCLUSIONS: The honeycomb-like
      structure of the left anterior descending coronary artery in our patient was
      suspected to be because of recanalization of a cardiogenic embolism. This
      structure may have been composed of relatively hard tissues, but was easily
      compressed by a stent implantation.

PMID- 27036625
TI  - Performance study of a laboratory model shallow solar pond with and without
      single transparent glass cover for solar thermal energy conversion applications.
AB  - The thermal performance of a shallow solar pond with and without the single
      transparent glass cover has been investigated experimentally. This experiment has
      been performed during the summer season of 2014 under the operational condition
      for five different storage volumes of water upto a maximum of 10liter. The pond
      performance is investigated in terms of the rate of energy collected and its
      collection efficiency. A Low Density Polyethylene (LDPE) black sheet liner of
      200MUm thickness was laid on all the interior sides of the pond for solar energy
      absorption. A clear transparent PVC plastic sheet of 150MUm thickness was laid
      over the water surface as evaporation suppressing membrane. Calibrated Copper
      constantan thermocouples were used to measure the temperatures of the system. A
      highest temperature of 81.5 degrees C has been achieved for the stored volume of
      2liter of water, when the pond was used with a single transparent glass cover of
      5mm thickness. When the shallow solar pond was used without the transparent glass
      cover the system attained a maximum temperature of 62 degrees C for the same
      stored volume of 2liter. A comparison between the two conditions of with and
      without the transparent glass cover, on the thermal performance of the SSP has
      been reported. A shallow solar pond system of the present type could be used us a
      source of warm water, of desired temperature, below 10 degrees C which are
      required for the domestic and industrial utilities. The global warming is
      increased day by day; inorder to reduce global warming a typical method of small
      scale shallow solar pond has been used to absorb the radiation from the sun to
      convert it to useful heat energy by the source of water. The SSP is an eco
      friendly way to generate energy without polluting our environment and in an
      environment safety manner. Based on environmental safety this study has
      experimentally investigated the thermal performance of the shallow solar pond.

PMID- 27036626
TI  - A model of gene expression based on random dynamical systems reveals modularity
      properties of gene regulatory networks.
AB  - Here we propose a new approach to modeling gene expression based on the theory of
      random dynamical systems (RDS) that provides a general coupling prescription
      between the nodes of any given regulatory network given the dynamics of each node
      is modeled by a RDS. The main virtues of this approach are the following: (i) it
      provides a natural way to obtain arbitrarily large networks by coupling together
      simple basic pieces, thus revealing the modularity of regulatory networks; (ii)
      the assumptions about the stochastic processes used in the modeling are fairly
      general, in the sense that the only requirement is stationarity; (iii) there is a
      well developed mathematical theory, which is a blend of smooth dynamical systems
      theory, ergodic theory and stochastic analysis that allows one to extract
      relevant dynamical and statistical information without solving the system; (iv)
      one may obtain the classical rate equations form the corresponding stochastic
      version by averaging the dynamic random variables (small noise limit). It is
      important to emphasize that unlike the deterministic case, where coupling two
      equations is a trivial matter, coupling two RDS is non-trivial, specially in our
      case, where the coupling is performed between a state variable of one gene and
      the switching stochastic process of another gene and, hence, it is not a priori
      true that the resulting coupled system will satisfy the definition of a random
      dynamical system. We shall provide the necessary arguments that ensure that our
      coupling prescription does indeed furnish a coupled regulatory network of random
      dynamical systems. Finally, the fact that classical rate equations are the small
      noise limit of our stochastic model ensures that any validation or prediction
      made on the basis of the classical theory is also a validation or prediction of
      our model. We illustrate our framework with some simple examples of single-gene
      system and network motifs.

PMID- 27036627
TI  - Emerging Early Actions to Bend the Curve in Sub-Saharan Africa's Nutrition
      Transition.
AB  - BACKGROUND: Sub-Saharan Africa is the last region to undergo a nutrition
      transition and can still avoid its adverse health outcomes. OBJECTIVE: The
      article explores emerging responses to "bend the curve" in sub-Saharan Africa's
      nutrition transition to steer public health outcomes onto a healthier trajectory.
      METHODS: Early responses in 3 countries at different stages of food system
      transformation are examined: South Africa-advanced, Ghana-intermediate, and
      Uganda-early. By comparing these with international experience, actions are
      proposed to influence nutrition and public health trajectories as Africa's food
      systems undergo rapid structural change. RESULTS: Arising from rapid urbanization
      and diet change, major public health problems associated with overweight are
      taking place, particularly in South Africa and among adult women. However, public
      health responses are generally tepid in sub-Saharan Africa. Only in South Africa
      have policy makers instituted extensive actions to combat overweight and
      associated noncommunicable diseases through regulation, education, and public
      health programs. Elsewhere, in countries in the early and middle stages of
      transition, public health systems continue to focus their limited resources
      primarily on undernutrition. Related pressures on the supply side of Africa's
      food systems are emerging that also need to be addressed. CONCLUSIONS: Three
      types of intervention appear most feasible: maternal and child health programs to
      simultaneously address short-term undernutrition problems while at the same time
      helping to reduce future tendencies toward overweigh; regulatory and fiscal
      actions to limit access to unhealthy foods; and modernization of Africa's
      agrifood food system through job skills training, marketing reforms, and food
      industry entrepreneurship.

PMID- 27036628
TI  - Post-ischemic treatment of WIB801C, standardized Cordyceps extract, reduces
      cerebral ischemic injury via inhibition of inflammatory cell migration.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Anti-inflammatory therapy has been intensively
      investigated as a potential strategy for treatment of cerebral stroke. However,
      despite many positive outcomes reported in animal studies, anti-inflammatory
      treatments have not proven successful in humans as yet. Although immunomodulatory
      activity and safety of Cordyceps species (Chinese caterpillar fungi) have been
      proven in clinical trials and traditional Asian prescriptions for inflammatory
      diseases, its anti-ischemic effect remains elusive. AIM OF THE STUDY: In the
      present study, therefore, we investigated the potential therapeutic efficacy of
      WIB801C, the standardized extract of Cordyceps militaris, for treatment of
      cerebral ischemic stroke. MATERIALS AND METHODS: The anti-chemotactic activity of
      WIB801C was assayed in cultured rat microglia/macrophages. Sprague-Dawley rats
      were subjected to ischemic stroke via either transient (1.5-h tMCAO and
      subsequent 24-h reperfusion) or permanent middle cerebral artery occlusion (pMCAO
      for 24-h without reperfusion). WIB801C was orally administered twice at 3- and 8
      h (50mg/kg each) after the onset of MCAO. Infarct volume, edema, blood brain
      barrier and white matter damages, neurological deficits, and long-term survival
      rates were investigated. The infiltration of inflammatory cells into ischemic
      lesions was assayed by immunostaining. RESULTS: WIB801C significantly decreased
      migration of cultured microglia/macrophages. This anti-chemotactic activity of
      WIB-801C was not mediated via adenosine A3 receptors, although cordycepin, the
      major ingredient of WIB801C, is known as an adenosine receptor agonist. Post
      ischemic treatment with WIB801C significantly reduced the infiltration of ED-1
      and MPO-positive inflammatory cells into ischemic lesions in tMCAO rats. WIB801C
      treated rats exhibited significantly decreased infarct volume and cerebral edema,
      less white matter and blood-brain barrier damages, and improved neurological
      deficits. WIB801C also improved survival rates over 34 days after ischemia onset.
      A significant reduction in infarct volume and neurobehavioral deficits by WIB801C
      was also observed in rats subjected to pMCAO. CONCLUSIONS: In summary, post
      ischemic treatment of WIB801C reduced infiltration of inflammatory cells into
      ischemic lesions via inhibition of chemotaxis, which confers long-lasting
      histological and neurological protection in ischemic brain. WIB801C may be a
      promising anti-ischemic drug candidate with clinically relevant therapeutic time
      window and safety.

PMID- 27036629
TI  - Kegan Liyan oral liquid ameliorates lipopolysaccharide-induced acute lung injury
      through inhibition of TLR4-mediated NF-kappaB signaling pathway and MMP-9
      expression.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kegan Liyan oral liquid (KGLY), a Chinese
      prescription modified from classic formulas Yin-Qiao-San (from TCM classic
      Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian),
      has been reported to exert heat-clearing and detoxifying effects and used
      extensively for the treatment of severe pulmonary diseases in clinics including
      influenza, cough and pneumonia. AIM OF THIS STUDY: The purpose of this study was
      to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced
      acute lung injury (ALI) in mice and to illuminate the underlying mechanisms.
      MATERIALS AND METHODS: Mice were orally administrated with KGLY (50, 100 and
      150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung
      tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung
      wet/dry (W/D) weight ratio, histopathological examinations and biochemical
      analyses. The cell counts, protein concentration, interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), necrosis factor-alpha (TNF-alpha), macrophage inflammatory
      protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH),
      myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile,
      the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF
      kappaB), as well as matrix metalloproteinases 9 (MMP-9) were determined by
      western blot assay. RESULTS: KGLY significantly prolonged mice survival time and
      ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell
      infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated
      LPS-induced acute pulmonary inflammation via decreasing the expressions of
      cytokines and chemokines (IL-1beta, IL-6, TNF-alpha, and MIP-2), enhanced the
      activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of
      MPO and MDA, and down-regulated the expressions of TLR4, NF-kappaB and MMP9.
      CONCLUSIONS: The results suggested that the relieving effect of KGLY against LPS
      induced ALI might be partially due to suppression of oxidative stress and
      inflammatory response, inhibition of TLR4-mediated NF-kappaB activation, and down
      regulation of MMP9 expression, indicating it may be a potential therapeutic agent
      for ALI.

PMID- 27036630
TI  - Translational Research - The Value of Family-Centered Care for Improving the
      Quality of Care for Children and their Families.

PMID- 27036631
TI  - Brachytherapy improves survival in primary vaginal cancer.
AB  - PURPOSE: Prospective, randomized data does not exist to guide treatment in
      primary vaginal cancer (PVC). We evaluated the impact of brachytherapy on
      survival in women with PVC. METHODS AND MATERIALS: Women who received
      radiotherapy for PVC were identified using the Surveillance, Epidemiology, and
      End Result database. Two retrospective cohorts were created; women who received
      external beam radiotherapy (EBRT) alone and those who received brachytherapy
      (alone or in combination of EBRT). Nearest-neighbor propensity score matching was
      used to balance the groups according to measured covariates. Cox proportional
      hazard regression modeling was used to estimate the effect of receipt of
      brachytherapy on survival. RESULTS: Two thousand five hundred seventeen vaginal
      cancer patients were identified. Squamous cell carcinoma made up 75% of tumors.
      Median overall survival (OS) for patients receiving EBRT alone was 3.6years (95%
      CI, 3.0-4.2years) versus 6.1years (95% CI 5.2-7.2years) for patients receiving
      brachytherapy (p=<0.001). Cox proportional hazard model revealed decrease risk of
      death among patients that received brachytherapy in the matched cohort (HR 0.77;
      95% CI 0.68-0.86). Brachytherapy reduced risk of death among patients in all
      stage groups. No patient demographic or tumor variables favored the use of EBRT
      alone. Brachytherapy was associated with a decreased risk of death for all FIGO
      stages. Brachytherapy benefited patients with squamous cell carcinoma (HR 0.80;
      95% CI 0.70-0.92) and adenocarcinoma (HR 0.69; 95% CI 0.49-0.95). Tumors larger
      than 5cm had the greatest benefit from brachytherapy (HR 0.68; 95% CI 0.50-0.91).
      CONCLUSIONS: Brachytherapy should be encouraged for all suitable patients with
      PVC.

PMID- 27036632
TI  - Nottingham Trent University and Makerere University School of Public Health
      partnership: experiences of co-learning and supporting the healthcare system in
      Uganda.
AB  - Partnerships between developed and developing country institutions are
      increasingly becoming important in addressing contemporary global health
      challenges faced by health systems. Inter-university health collaboration such as
      the Nottingham Trent University (UK) and Makerere University School of Public
      Health (Uganda) partnership provide opportunities for working together in
      training, research and service delivery while strengthening health systems. This
      paper shares the experiences, achievements and opportunities of this partnership
      in co-learning and supporting the health system in Uganda. This includes a
      project being implemented to strengthen the training, supervision and motivation
      of community health workers in rural Uganda. Training and research are a key
      focus of the partnership and have involved both staff and students of both
      institutions including guest lectures, seminars and conference presentations. The
      partnership's collaboration with stakeholders such as the Ministry of Health
      (Uganda) and local health authorities has ensured participation necessary in
      supporting implementation of sustainable interventions. The partnership uses
      several channels such as email, telephone, Skype, Dropbox and WhatsApp which have
      been useful in maintaining constant and effective communication. The challenges
      faced by the partnership include lack of funding to support student mobility, and
      varying academic schedules of the two institutions. The experiences and prospects
      of this growing partnership can inform other collaborations in similar settings. 

PMID- 27036633
TI  - High correlation of VAS pain scores after 2 and 6 weeks of treatment with VAS
      pain scores at 12 weeks in randomised controlled trials in rheumatoid arthritis
      and osteoarthritis: meta-analysis and implications.
AB  - BACKGROUND: Researchers in clinical trials in rheumatoid arthritis (RA) and
      osteoarthritis (OA) often measure pain levels with a visual analogue scale (VAS).
      Of interest to clinical practice and future clinical trial design are
      associations of change from baseline (CFB) between time points with predictive
      ability of earlier response for long-term treatment benefit. We assessed the
      association and predictive ability of CFB in VAS pain between 2, 6 and 12 weeks
      in randomised controlled trials (RCTs) of non-steroidal anti-inflammatory drugs
      (NSAIDs). METHODS: Aggregated VAS pain data at baseline and CFB at 2, 6 and 12
      weeks were collected from a systematic literature review of 176 RCTs in OA and
      RA. The predictive ability of earlier assessments for longer-term pain reduction
      was estimated using correlation and regression analyses. Analysis was performed
      using the R software package for statistical programming, version 3.1.1. RESULTS:
      Appropriate data were available from 50 RCTs (22,854 patients). Correlations
      between time points were high (weighted correlation coefficients between 2 and 6
      weeks, 0.84; between 2 and 12 weeks, 0.79; and between 6 and 12 weeks, 0.96). CFB
      at 6 weeks was highly predictive and close to CFB at 12 weeks (regression
      coefficient 0.9, 95 % confidence interval 0.9-1.0). CFB at 2 weeks was
      significantly associated with CFB at 12 (0.8, 0.7-0.8) and 6 weeks (0.9, 0.8
      1.0). CONCLUSIONS: The results showed that early analgesic response measured by
      VAS for pain beyond 2 weeks of treatment with a particular NSAID is likely to be
      predictive of response at 12 weeks. Failure to achieve desired pain relief in OA
      and RA after 2 weeks should trigger reassessment of dosage and/or analgesic.

PMID- 27036634
TI  - Laparoscopic pylorus-preserving pancreatoduodenectomy. Roux-en-y reconstruction
      with isolated pancreatic drainage (with video).

PMID- 27036635
TI  - A tablet-interfaced high-resolution microendoscope with automated image
      interpretation for real-time evaluation of esophageal squamous cell neoplasia.
AB  - BACKGROUND AND AIMS: In recent years high-resolution microendoscopy (HRME) has
      shown potential to improve screening for esophageal squamous cell neoplasia.
      Furthering its utility in a clinical setting, especially in lower-resource
      settings, could be accomplished by reducing the size and cost of the system as
      well as incorporating the ability of real-time, objective feedback. This article
      describes a tablet-interfaced HRME with fully automated, real-time image
      analysis. METHODS: The performance of the tablet-interfaced HRME was assessed by
      acquiring images from the oral mucosa in a normal volunteer. An automated, real
      time analysis algorithm was developed and evaluated using training, test, and
      validation images from a previous in vivo study of 177 patients referred for
      screening or surveillance endoscopy in China. The algorithm was then implemented
      in a tablet HRME that was used to obtain and analyze images from esophageal
      tissue in 3 patients. Images were displayed alongside the probability that the
      imaged region was neoplastic. RESULTS: The tablet-interfaced HRME demonstrated
      comparable imaging performance at a lower cost compared with first-generation
      laptop-interfaced HRME systems. In a post-hoc quantitative analysis, the
      algorithm identified neoplasia with a sensitivity and specificity of 95% and 91%,
      respectively, in the validation set compared with 84% and 95% achieved in the
      original study. CONCLUSIONS: The tablet-based HRME is a low-cost tool that
      provides quantitative diagnostic information to the endoscopist in real time.
      This could be especially beneficial in lower-resource settings for operators with
      less experience interpreting HRME images.

PMID- 27036636
TI  - The Impact of an Active Lifestyle on the Functional Fitness Level of Older Women.
AB  - The American College of Sports Medicine recommends that to maintain health,
      adults should engage in 150 min of moderate/vigorous physical activity (MVPA) per
      week. The purpose of the current study was to investigate the lowest MVPA dose
      possible to maintain functional fitness. Functional fitness was assessed using
      the Senior Fitness Test in 101 women (75.0 +/- 7.2 years) from two Midwestern
      communities. Accelerometer determined daily activity level was assessed for 7
      days as participants went about their normal daily activities. MVPA was
      determined via proprietary filtering, and time spent in this intensity was
      calculated. A 5-day average of time spent in MVPA was organized into four groups.
      ANOVAs revealed significant differences between activity groups on all functional
      fitness measures except back scratch and sit and reach. Results indicate that to
      maintain lower body function in older women, a threshold of 20 min/day of MVPA
      for 5 days is needed.

PMID- 27036637
TI  - Double- and Triple-Duty Caregiving Men: An Examination of Subjective Stress and
      Perceived Schedule Control.
AB  - Based on the stress process model of family caregiving, this study examined
      subjective stress appraisals and perceived schedule control among men employed in
      the long-term care industry (workplace-only caregivers) who concurrently occupied
      unpaid family caregiving roles for children (double-duty child caregivers), older
      adults (double-duty elder caregivers), and both children and older adults (triple
      duty caregivers). Survey responses from 123 men working in nursing home
      facilities in the United States were analyzed using multiple linear regression
      models. Results indicated that workplace-only and double- and triple-duty
      caregivers' appraised primary stress similarly. However, several differences
      emerged with respect to secondary role strains, specifically work-family
      conflict, emotional exhaustion, and turnover intentions. Schedule control also
      constituted a stress buffer for double- and triple-duty caregivers, particularly
      among double-duty elder caregivers. These findings contribute to the scarce
      literature on double- and triple-duty caregiving men and have practical
      implications for recruitment and retention strategies in the health care
      industry.

PMID- 27036639
TI  - Scent of aura? Clinical features of olfactory hallucinations during a migraine
      attack (OHM).
AB  - Introduction Olfactory hallucination during a migraine attack (OHM) is a rare
      phenomenon. At present, it is not considered a manifestation of migraine aura.
      Material and methods The clinical features of OHM were collected in 11 patients.
      Results Of the 11 patients, 10 had migraine without aura and one migraine with
      aura associated with OHM. Mean age at onset of headache and at appearance of OHM
      were respectively 17.8 and 32.3 years. Migraine average frequency was 3.9
      attacks/month, 19% of them being associated with OHM. The temporal pattern of OHM
      maintained the same characteristics in the different attacks. OHM onset was
      described as sudden ( n = 5), gradual ( n = 3), initially sudden and then gradual
      ( n = 2), or developing in a few seconds ( n = 1). In most of the cases ( n = 8)
      OHM lasted from 3 to 10 minutes; it persisted during the pain phase (2-24 hours)
      in only three patients. The type of the perceived smell was invariably constant
      in nine patients. Conclusion OHM features fulfilled the ICHD-III beta criteria
      for typical aura.

PMID- 27036640
TI  - Case report: Epicranial pain after radiotherapy for skull base meningioma - the
      first symptomatic epicrania fugax?
AB  - BACKGROUND: To date, no symptomatic forms of epicrania fugax (EF) have been
      reported. Here, we describe the first EF-type pain to be probably caused by an
      underlying disorder. CASE REPORT: A 77-year-old woman started suffering from left
      V1-V2 trigeminal neuralgia at 72 years of age. Neurologic examination was normal.
      Magnetic resonance imaging (MRI) showed a left middle sphenoid wing meningioma
      compressing the left trigeminal nerve medially. After trying several
      neuromodulators, she received stereotactic radiotherapy. One month later, the
      episodes of facial pain were significantly diminished, but she started feeling
      brief electric paroxysms across her left hemicranium that were clinically
      identical to those of backwards EF. Serial MRI showed persistence of the
      meningioma without changes. CONCLUSION: Although the pathogenesis of EF remains
      uncertain, this case is consistent with a symptomatic origin in the trigeminal
      root/pathway. The onset of the EF-like pain could have been caused by the
      compressive effect of the tumour or, most likely, by the radiation.

PMID- 27036641
TI  - Syndrome of transient headache and neurologic deficits with cerebrospinal fluid
      lymphocytosis presenting as acute neurological emergencies.
AB  - Background The syndrome of transient headache and neurologic deficits with
      cerebrospinal fluid lymphocytosis (HaNDL) is a self-limited benign disorder of
      unclear pathogenesis, with diverse clinical manifestations. Cases We report two
      unusual presentations of this entity. The first case developed a catastrophic
      picture, characterized by acute elevation of intracranial pressure, necessitating
      emergency life support. The second case presented with hyperacute-onset mixed
      aphasia and facial droop, masquerading as acute ischemia of the middle cerebral
      artery territory. Both patients made full recoveries. Conclusion The possibility
      of HaNDL should be considered in individuals presenting with unusual patterns of
      headaches and transient neurological symptoms. Our report will expand the
      spectrum of this disorder, which will help physicians not only to recognize the
      unusual manifestations of this rare disorder, but also consider potential
      therapeutic interventions.

PMID- 27036638
TI  - The influence of corticosteroid treatment on the outcome of influenza
      A(H1N1pdm09)-related critical illness.
AB  - BACKGROUND: Patients with 2009 pandemic influenza A(H1N1pdm09)-related critical
      illness were frequently treated with systemic corticosteroids. While
      observational studies have reported significant corticosteroid-associated
      mortality after adjusting for baseline differences in patients treated with
      corticosteroids or not, corticosteroids have remained a common treatment in
      subsequent influenza outbreaks, including avian influenza A(H7N9). Our objective
      was to describe the use of corticosteroids in these patients and investigate
      predictors of steroid prescription and clinical outcomes, adjusting for both
      baseline and time-dependent factors. METHODS: In an observational cohort study of
      adults with H1N1pdm09-related critical illness from 51 Canadian ICUs, we
      investigated predictors of steroid administration and outcomes of patients who
      received and those who did not receive corticosteroids. We adjusted for potential
      baseline confounding using multivariate logistic regression and propensity score
      analysis and adjusted for potential time-dependent confounding using marginal
      structural models. RESULTS: Among 607 patients, corticosteroids were administered
      to 280 patients (46.1%) at a median daily dose of 227 (interquartile range, 154
      443) mg of hydrocortisone equivalents for a median of 7.0 (4.0-13.0) days.
      Compared with patients who did not receive corticosteroids, patients who received
      corticosteroids had higher hospital crude mortality (25.5% vs 16.4%, p = 0.007)
      and fewer ventilator-free days at 28 days (12.5 +/- 10.7 vs 15.7 +/- 10.1, p <
      0.001). The odds ratio association between corticosteroid use and hospital
      mortality decreased from 1.85 (95% confidence interval 1.12-3.04, p = 0.02) with
      multivariate logistic regression, to 1.71 (1.05-2.78, p = 0.03) after adjustment
      for propensity score to receive corticosteroids, to 1.52 (0.90-2.58, p = 0.12)
      after case-matching on propensity score, and to 0.96 (0.28-3.28, p = 0.95) using
      marginal structural modeling to adjust for time-dependent between-group
      differences. CONCLUSIONS: Corticosteroids were commonly prescribed for H1N1pdm09
      related critical illness. Adjusting for only baseline between-group differences
      suggested a significant increased risk of death associated with corticosteroids.
      However, after adjusting for time-dependent differences, we found no significant
      association between corticosteroids and mortality. These findings highlight the
      challenges and importance in adjusting for baseline and time-dependent
      confounders when estimating clinical effects of treatments using observational
      studies.

PMID- 27036642
TI  - In Vitro and Pilot In Vivo Evaluation of a Bioactive Coating for Stent Grafts
      Based on Chondroitin Sulfate and Epidermal Growth Factor.
AB  - PURPOSE: To evaluate the potential of a bioactive coating based on chondroitin
      sulfate (CS) and tethered epidermal growth factor (EGF) for improvement of
      healing around stent grafts (SGs). MATERIALS AND METHODS: The impact of the
      bioactive coating on cell survival was tested in vitro on human vascular cells
      using polyethylene terephthalate films (PET) as a substrate. After being
      transferred onto a more "realistic" material (expanded polytetrafluoroethylene
      [ePTFE]), the durability and mechanical behavior of the coating and cell survival
      were studied. Preliminary in vivo testing was performed in a canine iliac
      aneurysm model reproducing type I endoleaks (three animals with one control and
      one bioactive SG for each). RESULTS: CS and EGF coatings significantly increased
      survival of human smooth muscle cells and fibroblasts compared with bare PET or
      ePTFE (P < .05). The coating also displayed good durability over 30 days
      according to enzyme-linked immunosorbent assay and cell survival tests. The
      coating did not affect mechanical properties of ePTFE and was successfully
      transferred onto commercial SGs for in vivo testing. No difference was observed
      on computed tomography and macroscopic examinations in endoleak persistence at 3
      months, but the bioactive coating deposited on the abluminal surface of the SG
      (exposed to the vessel wall) increased the percentage of healed tissue in the
      aneurysm. No adverse effect, such as neointima formation or thrombosis, was
      observed. CONCLUSIONS: The bioactive coating promoted in vitro cell survival,
      displayed good durability, and was successfully transferred onto a commercial SG.
      Preliminary in vivo results suggest improved healing around bioactive SGs.

PMID- 27036643
TI  - A case of persistent skin rash and rhinitis with immune system dysregulation
      onboard the International Space Station.

PMID- 27036644
TI  - Identification of Predictive Gene Markers for Multipotent Stromal Cell
      Proliferation.
AB  - Multipotent stromal cells (MSCs) are known for their distinctive ability to
      differentiate into different cell lineages, such as adipocytes, chondrocytes, and
      osteocytes. They can be isolated from numerous tissue sources, including bone
      marrow, adipose tissue, skeletal muscle, and others. Because of their
      differentiation potential and secretion of growth factors, MSCs are believed to
      have an inherent quality of regeneration and immune suppression. Cellular
      expansion is necessary to obtain sufficient numbers for use; however, MSCs
      exhibit a reduced capacity for proliferation and differentiation after several
      rounds of passaging. In this study, gene markers of MSC proliferation were
      identified and evaluated for their ability to predict proliferative quality.
      Microarray data of human bone marrow-derived MSCs were correlated with two
      proliferation assays. A collection of 24 genes were observed to significantly
      correlate with both proliferation assays (|r| >0.70) for eight MSC lines at
      multiple passages. These 24 identified genes were then confirmed using an
      additional set of MSCs from eight new donors using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). The proliferative potential of
      the second set of MSCs was measured for each donor/passage for confluency
      fraction, fraction of EdU+ cells, and population doubling time. The second set of
      MSCs exhibited a greater proliferative potential at passage 4 in comparison to
      passage 8, which was distinguishable by 15 genes; however, only seven of the
      genes (BIRC5, CCNA2, CDC20, CDK1, PBK, PLK1, and SPC25) demonstrated significant
      correlation with MSC proliferation regardless of passage. Our analyses revealed
      that correlation between gene expression and proliferation was consistently
      reduced with the inclusion of non-MSC cell lines; therefore, this set of seven
      genes may be more strongly associated with MSC proliferative quality. Our results
      pave the way to determine the quality of an MSC population for a particular
      cellular therapy in lieu of an extended in vitro or in vivo assay.

PMID- 27036645
TI  - Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like
      phenotype in adult mice.
AB  - Specific growth factors induce formation and differentiation of excitatory and
      inhibitory synapses, and are essential for brain development and function.
      Fibroblast growth factor 22 (FGF22) is important for specifying excitatory
      synapses during development, including in the hippocampus. Mice with a genetic
      deletion of FGF22 (FGF22KO) during development subsequently have fewer
      hippocampal excitatory synapses in adulthood. As a result, FGF22KO mice are
      resistant to epileptic seizure induction. In addition to playing a key role in
      learning, the hippocampus is known to mediate mood and anxiety. Here, we explored
      whether loss of FGF22 alters affective, anxiety or social cognitive behaviors in
      mice. We found that relative to control mice, FGF22KO mice display longer
      duration of floating and decreased latency to float in the forced swim test,
      increased immobility in the tail suspension test, and decreased preference for
      sucrose in the sucrose preference test, which are all suggestive of a depressive
      like phenotype. No differences were observed between control and FGF22KO mice in
      other behavioral assays, including motor, anxiety, or social cognitive tests.
      These results suggest a novel role for FGF22 specifically in affective behaviors.

PMID- 27036646
TI  - Electrophysiological alterations in a complex rat model of schizophrenia.
AB  - BACKGROUND: Psychiatric disorders are frequently accompanied by changes in brain
      electrical oscillations and abnormal auditory event related potentials. The goal
      of this study was to characterize these parameters of a new rat substrain showing
      several alterations related to schizophrenia. METHODS: Male rats of the new
      substrain, developed by selective breeding after combined subchronic ketamine
      treatment and postweaning social isolation, and naive Wistar ones group-housed
      without any interventions were involved in the present study. At the age of 3
      months, animals were implanted with cortical electroencephalography electrodes.
      Auditory evoked potentials during paired-click stimuli and power of oscillation
      in different frequency bands were determined with and without acute ketamine
      (20mg/kg) treatment. RESULTS: Regarding the auditory evoked potentials, the
      latency of P2 was delayed and the amplitude of N1 peak was lower in the new
      substrain. The new substrain showed increased power of oscillations in the theta,
      alpha and beta bands, while decreased power was detected in delta and gamma2
      bands (52-70Hz) compared with control animals. Acute ketamine treatment increased
      the gamma1 band (30-48Hz) power in both groups, while it elicited significant
      changes only in the new substrain in the total power and in alpha, beta and
      gamma2 bands. CONCLUSIONS: The validation of the translational utility of this
      new rat substrain by electrophysiological investigations revealed that these rats
      show abnormalities that may model a part of the neurophysiological deficits
      observed in schizophrenia.

PMID- 27036647
TI  - A novel isoquinoline compound abolishes chronic unpredictable mild stress-induced
      depressive-like behavior in mice.
AB  - Chronic unpredictable mild stress (CUMS) elicits aspects of cognitive and
      behavioral alterations that can be used to model comparable aspects of depression
      in humans. The aim of the present study was to investigate the antidepressant
      like potential of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a novel
      isoquinoline compound, in CUMS, a model that meets face, construct and predictive
      criteria for validity. Swiss mice were subjected to different stress paradigms
      daily for a period of 35 days to induce the depressive-like behavior. The animals
      received concomitant FDPI (0.1 and 1mg/kg, intragastric) or paroxetine (8mg/kg,
      intraperitoneal) and CUMS. The behavioral tests (splash test, tail suspension
      test, modified forced swimming test and locomotor activity) were performed. The
      levels of cytokines, corticosterone and adrenocorticotropic (ACTH) hormones were
      determined in the mouse prefrontal cortex and serum. The synaptosomal [(3)H]
      serotonin (5-HT) uptake, nuclear factor (NF)-kappaB, tyrosine kinase receptor
      (TrkB) and pro-brain-derived neurotrophic factor (BDNF) levels were determined in
      the mouse prefrontal cortex. CUMS induced a depressive-like behavior in mice,
      which was demonstrated in the modified forced swimming, tail suspension and
      splash tests. FDPI at both doses prevented depressive-like behavior induced by
      CUMS, without altering the locomotor activity of mice. FDPI at the highest dose
      prevented the increase in the levels of NF-kB, pro-inflammatory cytokines,
      corticosterone and ACTH and modulated [(3)H]5-HT uptake and the proBDNF/TrkB
      signaling pathway altered by CUMS. The present findings demonstrated that FDPI
      elicited an antidepressant-like effect in a model of stress-induced depression.

PMID- 27036648
TI  - Prepare for scare-Impact of threat predictability on affective visual processing
      in spider phobia.
AB  - The visual processing of emotional faces is influenced by individual's level of
      stress and anxiety. Valence unspecific affective processing is expected to be
      influenced by predictability of threat. Using a design of phasic fear
      (predictable threat), sustained anxiety (unpredictable threat) and safety (no
      threat), we investigated the magnetoencephalographic correlates and temporal
      dynamics of emotional face processing in a sample of phobic patients. Compared to
      non-anxious controls, phobic individuals revealed decreased parietal emotional
      attention processes during affective processing at mid-latency and late
      processing stages. While control subjects showed increasing parietal processing
      of the facial stimuli in line with decreasing threat predictability, phobic
      subjects revealed the opposite pattern. Decreasing threat predictability also led
      to increasing neural activity in the orbitofrontal and dorsolateral prefrontal
      cortex at mid-latency stages. Additionally, unpredictability of threat lead to
      higher subjective discomfort compared to predictability of threat and no threat
      safety condition. Our findings indicate that visual processing of emotional
      information is influenced by both stress induction and pathologic anxiety.

PMID- 27036649
TI  - Involvement of hippocampal NMDA receptors in retrieval of spontaneous object
      recognition memory in rats.
AB  - The involvement of hippocampal N-methyl-d-aspartate (NMDA) receptors in the
      retrieval process of spontaneous object recognition memory was investigated. The
      spontaneous object recognition test consisted of three phases. In the sample
      phase, rats were exposed to two identical objects several (2-5) times in the
      arena. After the sample phase, various lengths of delay intervals (24h-6 weeks)
      were inserted (delay phase). In the test phase in which both the familiar and the
      novel objects were placed in the arena, rats' novel object exploration behavior
      under the hippocampal treatment of NMDA receptor antagonist, AP5, or vehicle was
      observed. With 5 exposure sessions in the sample phase (experiment 1), AP5
      treatment in the test phase significantly decreased discrimination ratio when the
      delay was 3 weeks but not when it was one week. On the other hand, with 2
      exposure sessions in the sample phase (experiment 2) in which even vehicle
      injected control animals could not discriminate the novel object from the
      familiar one with a 3 week delay, AP5 treatment significantly decreased
      discrimination ratio when the delay was one week, but not when it was 24h.
      Additional experiment (experiment 3) showed that the hippocampal treatment of an
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      antagonist, NBQX, decreased discrimination ratio with all delay intervals tested
      (24h-3 weeks). Results suggest that hippocampal NMDA receptors play an important
      role in the retrieval of spontaneous object recognition memory especially when
      the memory trace weakens.

PMID- 27036651
TI  - Exercise amelioration of depression-like behavior in OVX mice is associated with
      suppression of NLRP3 inflammasome activation in hippocampus.
AB  - Exercise has benefit for perimenopause women in many ways, such as affective
      disorders. Our previous study has demonstrated that inflammation in hippocampus
      contributes to development of depression-like behavior in ovariectomized (OVX)
      rats. Recently, oligomerization domain-like receptor family pyrin domain
      containing 3 (NLRP3) inflammasome has been implicated to be involved in
      lipopolysaccharide (LPS)- and chronic stress-induced depression-like behavior in
      rodents. We sought to investigate whether ovariectomy-induced depression-like
      behavior is associated with NLRP3 inflammasome activation in brain and the effect
      of exercise on NLRP3 inflammasome activation in this model. The results showed
      that ovariectomy resulted in depression-like behavior in mice and an increase in
      levels of IL-1beta and IL-18 in hippocampus. Exercise ameliorated the depression
      like behavior and decreased levels of IL-1beta and IL-18 in hippocampus. The
      level of IL-1beta and IL-18 in hippocampus correlated to depression-like behavior
      in OVX mice. The levels of NLRP3, cleaved caspase-1 P10 and CD11b in hippocampus
      were increased in OVX mice compared with control group. Exercise could reduce the
      levels of NLRP3, cleaved caspase-1 P10 and CD11b in OVX mice. Our study suggests
      that NLRP3 inflammasome activation contribute to inflammation in hippocampus upon
      to deprivation of ovary. Exercise amelioration of depression-like behavior is
      associated with suppression of NLRP3 inflammasome activation in hippocampus of
      this model.

PMID- 27036650
TI  - Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating.
AB  - Binge eating is a dysregulated form of feeding behavior that occurs in multiple
      eating disorders including binge-eating disorder, the most common eating
      disorder. Feeding is a complex behavioral program supported through the function
      of multiple brain regions and influenced by a diverse array of receptor signaling
      pathways. Previous studies have shown the overexpression of the opioid
      neuropeptide nociceptin (orphanin FQ, N/OFQ) can induce hyperphagia, but the role
      of endogenous nociceptin receptor (NOP) in naturally occurring palatability
      induced hyperphagia is unknown. In this study we adapted a simple, replicable
      form of binge eating of high fat food (HFD). We found that male and female
      C57BL/6J mice provided with daily one-hour access sessions to HFD eat
      significantly more during this period than those provided with continuous 24h
      access. This form of feeding is rapid and entrained. Chronic intermittent HFD
      binge eating produced hyperactivity and increased light zone exploration in the
      open field and light-dark assays respectively. Treatment with the potent and
      selective NOP antagonist SB 612111 resulted in a significant dose-dependent
      reduction in binge intake in both male and female mice, and, unlike treatment
      with the serotonin selective reuptake inhibitor fluoxetine, produced no change in
      total 24-h food intake. SB 612111 treatment also significantly decreased non
      binge-like acute HFD consumption in male mice. These data are consistent with the
      hypothesis that high fat binge eating is modulated by NOP signaling and that the
      NOP system may represent a promising novel receptor to explore for the treatment
      of binge eating.

PMID- 27036652
TI  - Management of ureteral stenting for postrenal failure during pregnancy after
      ureteral reimplantation: a case report.
AB  - BACKGROUND: Vesicoureteral reflux is thought to predispose to urinary tract
      infection and renal scarring, and ureteral reimplantation in childhood remains
      the gold standard for its treatment. It has been reported that the risk of
      postrenal failure during pregnancy is increased among women with Politano
      Leadbetter ureteral reimplantation. In previous case reports on patients with
      progressive hydronephrosis and renal failure during pregnancy after ureteral
      reimplantation, percutaneous nephrostomy was always required, so there has been
      no information about the clinical management of such patients by ureteral
      stenting. Here we report a patient with a history of bilateral ureteral
      reimplantation, in whom severe hydronephrosis during pregnancy was managed with
      ureteral stents. CASE PRESENTATION: A primigravida with severe hydronephrosis was
      referred to us at 29 weeks of gestation. Bilateral Politano-Leadbetter ureteral
      reimplantation had been performed at the age of 3 years. She was hospitalized
      immediately, and bilateral ureteral stents were successfully inserted. Post
      obstructive diuresis occurred after the stents were placed. Urinary tract
      infection developed after removal of the urethral catheter 1 week later, but
      responded to antibiotic therapy and catheter replacement. Labor was induced at 39
      weeks of gestation, with vaginal delivery of a healthy male infant. Both stents
      were found to have spontaneously migrated into the urethra after delivery. Repeat
      stenting under spinal anesthesia was required to improve postpartum symptoms of
      back pain and fever. Right distal ureteral obstruction persisted at 6 months
      after delivery and repeat ureteral reimplantation is planned. CONCLUSIONS:
      General obstetricians will not necessarily pay attention to a history of Politano
      Leadbetter ureteral reimplantation, but these patients should undergo careful
      monitoring of renal function and urinary tract morphology during perinatal care.
      In the present case, ureteral stenting was effective for postrenal failure during
      pregnancy after ureteral reimplantation. If ureteral stenting is selected,
      attention should be paid to post-obstructive diuresis, infection, and stent
      migration.

PMID- 27036653
TI  - Disorders of the neonatal nasal cavity: Fundamentals for practice.
AB  - Neonatal nasal obstruction is a well-known clinical entity. Fortunately, it is
      rarely life-threatening and usually resolves with conservative management. As
      with most conditions, a systematic history and thorough physical examination are
      crucial for correct diagnosis and management. The initial diagnosis may be
      elusive and require either serial or more in-depth evaluations. Occasionally,
      examination may reveal structural abnormalities necessitating surgical
      intervention. Fortunately most of these abnormalities are amenable to surgery;
      however, a select few are notoriously difficult to treat. 

PMID- 27036654
TI  - Imipramine alters the sterol profile in Leishmania amazonensis and increases its
      sensitivity to miconazole.
AB  - BACKGROUND: Imipramine, a tricyclic antidepressant widely used clinically, has
      other pharmacological effects, such as antileishmanial activity. Tricyclic
      antidepressants interact with lipid bilayers, and some studies have shown that
      imipramine inhibits methyltransferases. Leishmania spp. produces compounds with
      an ergostane skeleton instead of a cholesterol skeleton, and the inhibition of
      enzymes of the sterol biosynthesis pathway is an interesting therapeutic target.
      Among these enzymes, C-24 methyltransferase has been suggested to play an
      essential role, as its inhibition kills the parasites. In this context, we
      investigated whether imipramine alters the biosynthesis of sterols in L.
      amazonensis and evaluated the efficacy of imipramine alone and in combination
      with miconazole, a classical inhibitor of another step in this pathway. METHODS:
      To analyze the interference of imipramine with sterol metabolism, promastigotes
      of L. amazonensis were cultured with medium alone, 15 or 30 MUM imipramine or 4
      MUM miconazole, and their lipids were extracted with methanol/chloroform/water
      (1:0.5:0.4 v/v) and analyzed by GC/MS. To assess the antileishmanial activity of
      the treatments, promastigotes of L. amazonensis were incubated with various
      concentrations of imipramine up to 100 MUM and up to 24 MUM miconazole.
      Promastigotes were also treated with the combination of imipramine and miconazole
      at concentrations up to 12.5 MUM of imipramine and 24 MUM of miconazole. Parasite
      growth was evaluated by the MTT assay. The fractional inhibitory concentration
      index (FICI) was calculated to determine whether there were synergistic effects.
      Peritoneal macrophages with and without L. amazonensis infection were treated
      with miconazole (0 - 16 MUM) or imipramine (0 to 50 MUM) for 72 hours. For assays
      of the combined treatment in amastigotes, the concentration of imipramine was
      fixed at 12.5 MUM and various concentrations of miconazole were used up to 16
      MUM. The infection rate was determined by counting the infected macrophages under
      a light microscope. FINDINGS: Promastigotes treated with imipramine accumulated
      cholesta-5,7,22-trien-3beta-ol and cholesta-7-24-dien- 3beta-ol, sterols that
      normally increase after treatment with classical inhibitors of C-24
      methyltransferase. The IC50 of miconazole in promastigotes decreased when it was
      used in combination with imipramine, resulting in an additive effect, with a FICI
      value of 0.83. Imipramine also showed activity against intracellular amastigotes
      and enhanced the activity of miconazole, without apparent toxicity to the host
      cells. CONCLUSIONS: Imipramine was confirmed to have antileishmanial activity in
      both forms of the parasite, affecting the sterol biosynthesis of the organisms.
      Using imipramine in combination with azoles may be advantageous for the treatment
      of leishmaniasis.

PMID- 27036655
TI  - Converging and Unique Mechanisms of Mechanotransduction at Adhesion Sites.
AB  - The molecular mechanisms by which physical forces control tissue development are
      beginning to be elucidated. Sites of adhesion between both cells and the
      extracellular environment [extracellular matrix (ECM) or neighboring cells]
      contain protein complexes capable of sensing fluctuations in tensile forces.
      Tension-dependent changes in the dynamics and composition of these complexes mark
      the transformation of physical input into biochemical signals that defines
      mechanotransduction. It is becoming apparent that, although the core constituents
      of these different adhesions are distinct, principles and proteins involved in
      mechanotransduction are conserved. Here, we discuss the current knowledge of
      overlapping and distinct aspects of mechanotransduction between integrin and
      cadherin adhesion complexes.

PMID- 27036656
TI  - Intradermal injection of a Tat Oyi-based therapeutic HIV vaccine reduces of 1.5
      log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART
      interruption in a phase I/II randomized controlled clinical trial.
AB  - BACKGROUND: A Tat Oyi vaccine preparation was administered with informed consent
      to 48 long-term HIV-1 infected volunteers whose viral loads had been suppressed
      by antiretroviral therapy (cART). These volunteers were randomized in double
      blind method into four groups (n = 12) that were injected intradermally with 0,
      11, 33, or 99 ug of synthetic Tat Oyi proteins in buffer without adjuvant at
      times designated by month 0 (M0), M1 and M2, respectively. The volunteers then
      underwent a structured treatment interruption between M5 and M7. RESULTS: The
      primary outcomes of this phase I/IIa clinical trial were the safety and lowering
      the extent of HIV RNA rebound after cART interruption. Only one undesirable event
      possibly due to vaccination was observed. The 33 ug dose was most effective at
      lowering the extent of HIV RNA and DNA rebound (Mann and Whitney test, p = 0.07
      and p = 0.001). Immune responses against Tat were increased at M5 and this
      correlated with a low HIV RNA rebound at M6 (p = 0.01). CONCLUSION: This study
      suggests in vivo that extracellular Tat activates and protects HIV infected
      cells. The Tat Oyi vaccine in association with cART may provide an efficient
      means of controlling the HIV-infected cell reservoir.

PMID- 27036657
TI  - Life review in advanced age: qualitative research on the 'start in life' of 90
      year-olds in the Lothian Birth Cohort 1921.
AB  - BACKGROUND: This research report presents findings on 'start in life' from a
      qualitative study of 90-year-olds from the Lothian Birth Cohort 1921. The study
      aimed to contextualise the LBC1921 cohort in time and place, describe cohort
      members' experiences of family and schooling and stimulate further inquiry into
      the relationships between 'start in life' and risk and resilience factors
      relating to longevity and healthy ageing. Scottish education and family life in
      the early 1930s are briefly described. METHODS: Life review questionnaire: A
      qualitative Life Review Questionnaire was developed, requiring free-text
      handwritten responses. Its 'Start in Life' section focused on schooling and
      family support. SAMPLE: Wave 4 of the Lothian Birth Cohort 1921 involved testing
      129 members near to their 90(th) birthday. They reside largely in Edinburgh and
      its environs. The Life Review Questionnaire was administered to 126 participants,
      54 % women. Qualitative analysis: Thematic analysis was the qualitative technique
      used to categorise, code and extract meaning from questionnaire text. Narratives
      were extracted from the data to present illustrative stories. RESULTS: Narratives
      of start in life gave contextual description. Thematic analysis showed LBC1921
      members enjoying their schooling, highlighting teachers, academic achievement,
      school activities and school friendships. Personal qualities, family
      circumstances and aspects of schooling sometimes hindered educational
      performance. Family life was recalled mostly with warmth and parents were often
      portrayed as valuing education and supporting learning and development. Family
      adversity from poverty, parental illness and parental death was often mitigated
      by support from parents (or the remaining parent). Overall, most cohort members
      believed that they had got off to a good 'start in life'. CONCLUSIONS: This
      qualitative investigation of 'start in life' adds context and richness to
      quantitative investigations of the sizeable LBC1921 cohort, stimulating fresh
      insights and hypotheses into the relationship between child risk and resilience
      factors that may influence ageing. It demonstrates the utility and wider
      application of the Life Review Questionnaire. Although the surviving cohort is
      not representative of their childhood peers, their words provide insight into the
      processes of weaving experience and memory into a rich texture of meanings that
      may help create wellbeing across a lifetime.

PMID- 27036658
TI  - Long-term non-invasive ventilation reduces readmissions in COPD patients with two
      or more episodes of acute hypercapnic respiratory failure.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients who have had an
      episode of acute hypercapnic respiratory failure (AHRF) have a large 1-year risk
      of death or readmission. Acute non-invasive ventilation (NIV) has been shown to
      be an effective treatment of AHRF; and long-term NIV (LTNIV) has been shown to be
      an effective treatment of chronic respiratory failure in stable hypercapnic COPD.
      We investigated the effects of LTNIV in a group of patients with severe, unstable
      COPD: frequent admissions and multiple previous episodes of AHRF treated with
      NIV. METHODS: We conducted a retrospective analysis of 20 COPD patients treated
      with LTNIV after two or more episodes of AHRF during 1 year. RESULTS: The mean
      number of AHRF episodes decreased from 2.44 in the year prior to LTNIV initiation
      to 0.44 in the year following (p<0.0001). The median number of admissions
      decreased from 5.19 to 1.88 (p=0.0092). Four patients (20%) died in 1 year. LTNIV
      tended to reduce arterial CO2. No changes were found in lung function.
      CONCLUSIONS: LTNIV seems effective in reducing recurrent AHRF and readmissions in
      a highly select group of patients with severe, unstable COPD and frequent AHRF.

PMID- 27036659
TI  - Helium-neon laser irradiation of cryopreserved ram sperm enhances cytochrome c
      oxidase activity and ATP levels improving semen quality.
AB  - This study examines whether and how helium-neon laser irradiation (at fluences of
      3.96-9 J/cm(2)) of cryopreserved ram sperm helps improve semen quality. Pools (n
      = 7) of cryopreserved ram sperm were divided into four aliquots and subjected to
      the treatments: no irradiation (control) or irradiation with three different
      energy doses. After treatment, the thawed sperm samples were compared in terms of
      viability, mass and progressive sperm motility, osmotic resistance, as well as
      DNA and acrosome integrity. In response to irradiation at 6.12 J/cm(2), mass
      sperm motility, progressive motility and viability increased (P < 0.05), with no
      significant changes observed in the other investigated properties. In parallel,
      an increase (P < 0.05) in ATP content was detected in the 6.12 J/cm(2)-irradiated
      semen samples. Because mitochondria are the main cell photoreceptors with a major
      role played by cytochrome c oxidase (COX), the COX reaction was monitored using
      cytochrome c as a substrate in both control and irradiated samples. Laser
      treatment resulted in a general increase in COX affinity for its substrate as
      well as an increase in COX activity (Vmax values), the highest activity obtained
      for sperm samples irradiated at 6.12 J/cm(2) (P < 0.05). Interestingly, in these
      irradiated sperm samples, COX activity and ATP contents were positively
      correlated, and, more importantly, they also showed positive correlation with
      motility, suggesting that the improved sperm quality observed was related to
      mitochondria-laser light interactions. 

PMID- 27036660
TI  - Fertility after two doses of PGF2alpha concurrently or at 6-hour interval on the
      day of CIDR removal in 5-day CO-Synch progesterone-based synchronization
      protocols in beef heifers.
AB  - Timed artificial insemination protocols in beef cattle are designed to
      synchronize ovulation in a greater proportion of females while simultaneously
      achieving acceptable pregnancy rates and a concise calving season. Protocols
      achieving such goals reduce time and labor associated with estrus detection and
      make advanced reproductive technologies implementable for beef producers. The
      objective of the study was to determine the effect of three different PGF2alpha
      (PGF) dosage schemes on artificial insemination (AI) pregnancy rates in beef
      heifers. We hypothesized that two doses of PGF administered concurrently at the
      time of controlled internal drug release (CIDR) removal would attain similar
      pregnancy rates compared with two doses given 6-hours apart-one at CIDR removal
      and the next 6 hours later in the 5-day CO-Synch progesterone-based
      synchronization protocol. Angus heifers (n = 875) at six locations in Washington,
      Idaho, and Oregon states were included in this study. Heifers within locations
      were assigned a body condition score (BCS). All heifers received a CIDR (1.38 g
      of progesterone) and 100 MUg IM of GnRH on Day 0. The CIDRs were removed on Day
      5, heifers were randomly allocated to one of three protocol groups: 1PGF (n =
      291), received 25 mg IM of dinoprost (PGF); 2CO-PGF (n = 291), received 50 mg IM
      of dinoprost at CIDR removal, 2PGF (n = 293), received 25 mg IM of dinoprost at
      CIDR removal, and an additional 25 mg IM of dinoprost 6 hours later. Each heifer
      was given GnRH (100 MUg, IM) and artificially inseminated at 56 hours after CIDR
      removal. Heifers were examined for pregnancy status between 50 and 70 days after
      AI to determine time of conception. A mixed-model procedure (PROC GLIMMIX of SAS)
      was used to evaluate the effect of treatments (1PGF, 2CO-PGF, and 2PGF) on AI
      pregnancy rates. Models included were treatments, BCS categories (<=5 and >5),
      and treatment by BCS category interaction. Location (state), handling facilities,
      handlers, inseminators, and AI sires were included as a random effect in the
      model. The 2PGF group had greater AI pregnancy rate of 63.6% (185/291), compared
      with the 2CO-PGF group at 51.9% (151/291) and 1PGF group at 54.9% (161/293; P <
      0.001). An AI pregnancy rate of 50% (104/208) was observed for heifers with BCS
      less than or equal to 5 versus 58.9% (393/667) for heifers with BCS greater than
      5 (P < 0.05). Location did not influence the AI pregnancy rate (P > 0.1). In
      conclusion, beef heifers received two 25-mg doses of PGF at 6-hour interval on
      Day 5 at CIDR insert removal in a 5-day CO-Synch + CIDR synchronization protocols
      achieved greater pregnancy compared with heifers received 50 mg of PGF
      concurrently at CIDR removal. 

PMID- 27036661
TI  - A randomized control hands-on defibrillation study-Barrier use evaluation.
AB  - INTRODUCTION: Chest compressions and defibrillation are the only therapies proven
      to increase survival in cardiac arrest. Historically, rescuers must remove hands
      to shock, thereby interrupting chest compressions. This hands-off time results in
      a zero blood flow state. Pauses have been associated with poorer neurological
      recovery. METHODS: This was a blinded randomized control cadaver study evaluating
      the detection of defibrillation during manual chest compressions. An active
      defibrillator was connected to the cadaver in the sternum-apex configuration. The
      sham defibrillator was not connected to the cadaver. Subjects performed chest
      compressions using 6 barrier types: barehand, single and double layer nitrile
      gloves, firefighter gloves, neoprene pad, and a manual chest
      compression/decompression device. Randomized defibrillations (10 per barrier
      type) were delivered at 30 joules (J) for bare hand and 360J for all other
      barriers. After each shock, the subject indicated degree of sensation on a VAS
      scale. RESULTS: Ten subjects participated. All subjects detected 30j shocks
      during barehand compressions, with only 1 undetected real shock. All barriers
      combined totaled 500 shocks delivered. Five (1%) active shocks were detected,
      1(0.2%) single layer of Nitrile, 3(0.6%) with double layer nitrile, and 1(0.2%)
      with the neoprene barrier. One sham shock was reported with the single layer
      nitrile glove. No shocks were detected with fire gloves or compression
      decompression device. All shocks detected barely perceptible (0.25(+/-0.05)cm on
      10cm VAS scale). CONCLUSIONS: Nitrile gloves and neoprene pad prevent (99%)
      responder's detection of defibrillation of a cadaver. Fire gloves and compression
      decompression device prevented detection.

PMID- 27036662
TI  - Influence of the temperature on the moment of awakening in patients treated with
      therapeutic hypothermia after cardiac arrest.
AB  - INTRODUCTION: Target temperature management (TTM) has shown to reduce brain
      damage after an out-of-hospital cardiac arrest (CA), but the time to neurological
      recovery is not defined yet. We sought to determine the time these patients need
      to regain consciousness, as well as factors associated with a late post-arrest
      awakening. METHODS: We performed a retrospective analysis of patients cooled to
      32-34 degrees C during 24h after CA, who regained neurological responsiveness
      after rewarming. We measured the time until awakening, defined as obedience to
      verbal commands. RESULTS: We included 163 CA survivors (84.7% male, 60.2 years)
      who regained consciousness after TTM: target temperature was either 32 degrees C
      (36.2%), 33 degrees C (56.4%) or 34 degrees C (6.7%). Mean time of awakening was
      3.8 days. Thirty-four patients (20.9%) regained neurological responsiveness after
      5 days after CA. All of them had been cooled to either 32 degrees C (18 patients)
      or 33 degrees C (16), and no patient cooled to 34 degrees C awakened after day 5.
      A lower target temperature was associated with a later awakening (p<0.001). The
      time to advanced cardiopulmonary resuscitation (CPR) was shorter among the early
      awakers (p=0.04), but we found no other predictors of an earlier awakening.
      CONCLUSIONS: A high proportion of CA survivors induced to TTM regained
      consciousness after 5 days, and cooling to a lower target temperature may
      influence on a late neurological recovery. Therefore, withdrawal of life
      supporting treatment should be delayed to more than 5 days in patients cooled to
      33 degrees C or less. Time to advanced CPR was found to be a predictor of early
      awakening.

PMID- 27036663
TI  - Automated assessment of early hypoxic brain edema in non-enhanced CT predicts
      outcome in patients after cardiac arrest.
AB  - INTRODUCTION: Early prediction of potential neurological recovery in patients
      after cardiac arrest is challenging. Recent studies suggest that the
      densitrometic gray-white matter ratio (GWR) determined from cranial computed
      tomography (CT) scans may be a reliable predictor of poor outcome. We evaluated
      an automated, rater independent method to determine GWR in CT as an early
      objective imaging predictor of clinical outcome. METHODS: We analyzed imaging
      data of 84 patients after cardiac arrest that underwent noncontrast CT within 24h
      after arrest. To determine GWR in CT we applied two methods using a recently
      published automated probabilistic gray-white matter segmentation algorithm
      (GWR_aut) and conventional manual measurements within gray-white regions of
      interest (GWR_man). Neurological outcome was graded by the cerebral performance
      category (CPC). As part of standard routine CPC was assessed by the treating
      physician in the intensive care unit at admission and at discharge to normal
      ward. The performance of GWR measures (automated and manual) to predict the
      binary clinical endpoints of poor (CPC3-5) and good outcome (CPC1-2) was assessed
      by ROC analysis with increasing discrimination thresholds. Results of GWR_aut
      were compared to GWR_man of two raters. RESULTS: Of 84 patients, 55 (65%) showed
      a poor outcome. ROC curve analysis revealed reliable outcome prediction of
      GWR_aut (AUC 0.860) and GWR_man (AUC 0.707 and 0.699, respectively). Predictive
      power of GWR_aut was higher than GWR_man by each rater (p=0.019 and p=0.021,
      respectively) at an optimal cut-off of 1.084 to predict poor outcome (optimal
      criterion with 92.7% sensitivity, 72.4% specificity). Interrater reliability of
      GWR_man by intra-class correlation coefficient (ICC) was moderate (0.551).
      CONCLUSION: Automated quantification of GWR in CT may be used as an objective
      observer-independent imaging marker for outcome in patients after cardiac arrest.

PMID- 27036664
TI  - How scary! An analysis of visual communication concerning genetically modified
      organisms in Italy.
AB  - Several studies provide evidence of the role of written communication in
      influencing public perception towards genetically modified organisms, whereas
      visual communication has been sparsely investigated. This article aims to
      evaluate the exposure of the Italian population to scary genetically modified
      organism-related images. A set of 517 images collected through Google are
      classified considering fearful attributes, and an index that accounts for the
      scary impact of these images is built. Then, through an ordinary least-squares
      regression, we estimate the relationship between the Scary Impact Index and a set
      of variables that describes the context in which the images appear. The results
      reveal that the first (and most viewed) Google result images contain the most
      frightful contents. In addition, the agri-food sector in Italy is strongly
      oriented towards offering a negative representation of genetically modified
      organisms. Exposure to scary images could be a factor that affects the negative
      perception of genetically modified organisms in Italy.

PMID- 27036665
TI  - Contemporary understanding of riots: Classical crowd psychology, ideology and the
      social identity approach.
AB  - This article explores the origins and ideology of classical crowd psychology, a
      body of theory reflected in contemporary popularised understandings such as of
      the 2011 English 'riots'. This article argues that during the nineteenth century,
      the crowd came to symbolise a fear of 'mass society' and that 'classical' crowd
      psychology was a product of these fears. Classical crowd psychology pathologised,
      reified and decontextualised the crowd, offering the ruling elites a perceived
      opportunity to control it. We contend that classical theory misrepresents crowd
      psychology and survives in contemporary understanding because it is ideological.
      We conclude by discussing how classical theory has been supplanted in academic
      contexts by an identity-based crowd psychology that restores the meaning to crowd
      action, replaces it in its social context and in so doing transforms theoretical
      understanding of 'riots' and the nature of the self.

PMID- 27036669
TI  - Vitamin D status and supplementation before and after bariatric surgery: a
      comprehensive literature review.
AB  - BACKGROUND: Bariatric surgery is the most effective long-term weight loss method.
      The most common procedures are Roux-en-Y gastric bypass (RYGB) and vertical
      sleeve gastrectomy (VSG). Bariatric patients are at high risk of vitamin D
      deficiency (VDD) and insufficiency (VDI), which are associated with skeletal and
      nonskeletal ailments. There is no consensus regarding the optimal treatment for
      VDD/VDI in bariatric patients. OBJECTIVES: To critically examine the literature
      on vitamin D status (serum 25[OH]D concentrations) pre- and postbariatric surgery
      as well as supplementation regimens currently used. METHODS: We searched PubMed,
      Embase, and Cochrane from inception to May 2015 for articles relating to vitamin
      D, RYGB, and VSG. Of 208 citations retrieved, 30 were included. RESULTS:
      Preoperative VDD (<20 ng/mL) ranged from 13% to 90%, while VDI (<30 ng/mL) was
      found in up to 98%. Prevalence remained similar postoperatively and was highest
      after RYGB. Most studies found dosages<800 IU daily insufficient postbariatric
      surgery. Other studies examined the effectiveness of dosages between 1000 and
      5000 IU daily, reaching similar conclusions. Several studies suggested using
      50,000 IU weekly plus a daily dose. No studies reported optimization.
      CONCLUSIONS: It is widely accepted that serum 25(OH)D concentrations above 30
      ng/mL are optimal; however, current postbariatric vitamin D supplementation fails
      to raise 25(OH)D above that level universally. This review highlights both the
      great need and the lack of consensus on the optimal supplementation regimen
      (dosage and frequency) for pre- and postbariatric patients. Future studies should
      investigate multiple regimens and attempt to identify methods for personalizing
      these regimens if found necessary.

PMID- 27036670
TI  - [Injury mechanisms in extreme violence settings].
AB  - Extreme violence events are consequence of current world-wide economic, political
      and social conditions. Injury patterns found among victims of extreme violence
      events are very complex, obeying several high-energy injury mechanisms. In this
      article, we present the basic concepts of trauma kinematics that regulate the
      clinical approach to victims of extreme violence events, in the hope that
      clinicians increase their theoretical armamentarium, and reflecting on obtaining
      better outcomes. 

PMID- 27036671
TI  - [Non-surgical management after blunt traumatic liver injuries: A review article].
AB  - Hepatic trauma is a common cause for admissions in the Emergency Room. Currently,
      non-surgical management is the standard treatment in haemodynamically stable
      patients with a success rate of around 85 to 98%. This haemodynamic stability is
      the most important factor in selecting the appropriate patient. Adjuncts in non
      surgical management are angioembolisation, image-guided drainage and endoscopic
      retrograde cholangiopancreatography. Failure in non-surgical management is
      relatively rare but potentially fatal, and needs to be recognised and
      aggressively treated as early as possible. The main cause of failure in non
      surgical management is persistent haemorrhage. The aim of this paper is to
      describe current evidence and guidelines that support non-surgical management of
      liver injuries in blunt trauma. 

PMID- 27036672
TI  - [Colorectal anastomosis using a compression device].
AB  - BACKGROUND: The most severe complication following an intestinal anastomosis is
      the dehiscence with the consequent development of sepsis, fistulas, stenosis, and
      death. For this reason the compression anastomosis (NiTi) system was developed,
      with the aim of reducing these complications. MATERIAL AND METHODS: A
      retrospective study was conducted, from 1 June 2012 to 30 August 2014, on total
      of 14 patients operated on the Humanitas Hospital Medical Group Coyoacan, the
      ASMED, and Clinica Medica Sur. The subjects were predominantly male 65%, a mean
      age of 58 years, with range 30-79 years. RESULTS: A total of 14 patients were
      included. The indication for surgery was complicated diverticular disease Hinchey
      II-III (36%), and the procedures performed were: 6 (43%) left hemicolectomy with
      primary end to end compression anastomosis, 2 (14%) major complications
      (dehiscence wall and anastomosis), 1 (7%) minor complication (infection of the
      soft tissues). There was a mean 98ml (range 20-300ml) of intraoperative bleeding,
      with start of oral feeding on the second day, a mean hospital stay of 4 days
      (range 2-10), one patient with ileo-rectal anastomosis dehiscence presented on
      the 4th post-operative day, and performing anastomosis with stapling device and
      loop ileostomy. Stenosis developed in 7% during follow-up and was resolved with a
      new anastomosis stapler. CONCLUSIONS: The NiTi device is an additional
      alternative for colorectal anastomosis, mainly in low anastomosis, obtaining good
      results in this study without major complications.

PMID- 27036673
TI  - Management of Acute Mesenteric Ischemia: A Critical Review and Treatment
      Algorithm.
AB  - BACKGROUND: Acute mesenteric ischemia (AMI) due to a sudden loss or decrease in
      blood perfusion to the mesentery represents a highly lethal condition. However,
      the optimal surgical management remains debatable and merits a more clear
      recommendation based on a higher level of evidence. METHODS: A systematic review
      of articles published between 2000 and 2013 was performed. Patients were divided
      into endovascular treatment (ET), open surgery (OS), and hybrid technique (HT)
      groups. Data of patients' demographics, procedural information, clinical outcomes
      including mortality, morbidity, primary patency rate, technique success, primary
      intestinal resection rate, and second-look laparotomy rate, and follow-up were
      all retrieved. Comparison between the ET and the OS groups was made using 2-sided
      Student t test and 2-sided chi(2) test or Fisher exact test where appropriate.
      RESULTS: Twenty-eight articles with a total of 1110 patients were included for
      the review. The ET group had lower in-hospital mortality and morbidity but
      similar survival rate during follow-up compared to the OS group. The primary
      patency rate was higher in the ET group. The overall bowel resection rate was
      lower in the ET group, and nearly every patient in the cohort who required second
      look laparotomy required bowel resection. The HT group seemed to have the lowest
      mortality and acceptable second-look laparotomy rate and morbidity. Comparison
      between the HT group and other groups was not possible due to the limited number
      of cases available for review. CONCLUSION: Endovascular treatment may serve as a
      first-line therapy for select patients when there is a low suspicion for
      intestinal necrosis. Open surgery should be reserved for emergency conditions
      requiring exploratory laparotomy. Hybrid technique may be an especially effective
      approach for treating AMI, with low morbidity and mortality, although further
      studies are required comparing it to OS and ET.

PMID- 27036674
TI  - Superior Vena Cava Obstruction Complicated by Upper Extremity Deep Vein
      Thrombosis: A Novel Endovascular Approach.
AB  - Superior vena cava obstruction (SVCO) and associated thrombus formation can occur
      in patients with upper mediastinal or right apical masses. While stenting is
      useful in relieving obstruction, it can facilitate the passage of upper extremity
      deep vein thrombus to the pulmonary arterial tree, resulting in a potentially
      fatal pulmonary embolism (PE). We present a case that illustrates a novel
      technique, which protects the patient from PE while also relieving the SVCO. This
      involves placing an inferior vena cava filter in an inverted position within a
      superior vena cava (SVC) stent to capture emboli. This procedure offers a
      potentially lifesaving endovascular therapeutic option to patients who would
      otherwise be deemed unsuitable for SVC stenting. 

PMID- 27036675
TI  - Endovascular Treatment of a Dorsalis Pedis Artery Pseudoaneurysm.
AB  - Pseudoaneurysm of the dorsalis pedis artery (DPA) is an extremely rare entity
      that most commonly occurs secondary to trauma or surgery. All reported cases
      describe surgical treatment. We illustrate a case of enlarging DPA pseudoaneurysm
      causing pain and disability in a 49-year-old woman who was treated with
      transcatheter embolization and pseudoaneurysm aspiration resulting in near
      immediate resolution of symptoms. 

PMID- 27036676
TI  - Looking into aqueous humor through metabolomics spectacles - exploring its
      metabolic characteristics in relation to myopia.
AB  - Aqueous humor is the transparent fluid found in the anterior chamber of the eye
      that provides the metabolic requirements to the avascular tissues surrounding it.
      Despite the fact that metabolomics could be a powerful tool in the
      characterization of this biofluid and in revealing metabolic signatures of common
      ocular diseases such as myopia, it has never to our knowledge previously been
      applied in humans. In this research a novel method for the analysis of aqueous
      humor is presented to show its application in the characterization of this
      biofluid using CE-MS. The method was extended to a dual platform method (CE-MS
      and LC-MS) in order to compare samples from patients with different severities of
      myopia in order to explore the disease from the metabolic phenotype point of
      view. With this method, a profound knowledge of the metabolites present in human
      aqueous humor has been obtained: over 40 metabolites were reproducibly and
      simultaneously identified from a low volume of sample by CE-MS, including among
      others, a vast number of amino acids and derivatives. When this method was
      extended to study groups of patients with high or low myopia in both CE-MS and LC
      MS, it has been possible to identify over 20 significantly different metabolite
      and lipid signatures that distinguish patients based on the severity of myopia.
      Among these, the most notable higher abundant metabolites in high myopia were
      aminooctanoic acid, arginine, citrulline and sphinganine while features of low
      myopia were aminoundecanoic acid, dihydro-retinoic acid and cysteinylglycine
      disulfide. This dual platform approach offered complementarity such that
      different metabolites were detected in each technique. Together the experiments
      presented provide a whelm of valuable information about human aqueous humor and
      myopia, proving the utility of non-targeted metabolomics for the first time in
      analyzing this type of sample and the metabolic phenotype of this disease. 

PMID- 27036677
TI  - Editorial Comment.

PMID- 27036678
TI  - Author Reply.

PMID- 27036679
TI  - Editorial Comment.

PMID- 27036680
TI  - Editorial Comment.

PMID- 27036681
TI  - Author Reply.

PMID- 27036682
TI  - Author Reply.

PMID- 27036683
TI  - Editorial Comment.

PMID- 27036684
TI  - Editorial Comment.

PMID- 27036685
TI  - Editorial Comment.

PMID- 27036686
TI  - Author Reply.

PMID- 27036687
TI  - Editorial Comment.

PMID- 27036688
TI  - Author Reply.

PMID- 27036689
TI  - [Erratum of "Non-pharmacological analgesia in Spanish neonatal units"].

PMID- 27036690
TI  - Corrigendum to "Testosterone related to age and life-history stages in male
      baboons and geladas" [Horm. Behav. 56/4 (2009) 472-480].

PMID- 27036691
TI  - Biological v. psychosocial treatments: a myth about pharmacotherapy v.
      psychotherapy.
AB  - Despite evidence for their comparable efficacy, psychotherapy faces a dramatic
      decline relative to pharmacotherapy in psychiatry. A deep ideological reason for
      this decline centres on the belief that psychotherapy is a psychosocial treatment
      whereas pharmacotherapy is a biological treatment. Modern cognitive neuroscience
      demonstrates that this distinction is a myth. 

PMID- 27036692
TI  - From asylum to psychiatric hospital in West Africa - extra.

PMID- 27036693
TI  - Counterpoint: clinical neuroscience is not ready for clinical use.
AB  - Radical proposals are being made to change the practice, teaching and research
      basis of psychiatry to that of clinical neuroscience. Such changes would affect
      practice via what is studied, published, recommended as standard treatment and
      what is decided in medico-legal forums. These proposed changes are very premature
      and misguided. Here, I refute these proposals. 

PMID- 27036694
TI  - A Theory of Human Motivation by Abraham H. Maslow - reflection.

PMID- 27036695
TI  - Resolving mental illness stigma: should we seek normalcy or solidarity?
AB  - Two approaches have emerged to deal with the stigma of mental illness: normalcy,
      where people with mental illness are framed as 'just like everyone else'; and
      solidarity, where the public agrees to stand with those with mental illness
      regardless of their symptoms. Pros and cons of each approach are considered. 

PMID- 27036696
TI  - NICE v. SIGN on psychosis and schizophrenia: same roots, similar guidelines,
      different interpretations.
AB  - A recent editorial claimed that the 2014 National Institute for Health and Care
      Excellence (NICE) guideline on psychosis and schizophrenia, unlike its equivalent
      2013 Scottish Intercollegiate Guidelines Network (SIGN) guideline, is biased
      towards psychosocial treatments and against drug treatments. In this paper we
      underline that the NICE and SIGN guidelines recommend similar interventions, but
      that the NICE guideline has more rigorous methodology. Our analysis suggests that
      the authors of the editorial appear to have succumbed to bias themselves. 

PMID- 27036697
TI  - Invited commentary on ... NICE v. SIGN on psychosis and schizophrenia.
AB  - How contemporaneous guidelines interpret similar data is interesting but not
      relevant here. Conflicts of interest are important and various. Two clinically
      important recommendations in the National Institute for Health and Care
      Excellence (NICE) guideline CG178 deserve re-visiting. 

PMID- 27036698
TI  - An 18th-century view of demonomania. 2: Vampirism - stories - psychiatry in
      history.

PMID- 27036700
TI  - Treatment is necessary!

PMID- 27036701
TI  - Authors' reply.

PMID- 27036702
TI  - 'Lethal discrimination', ideology and social justice.

PMID- 27036704
TI  - Ahead in mental sciences: cultural, environmental and social campaigns.

PMID- 27036706
TI  - Pathways through care of severely mentally ill individuals experiencing multiple
      public crisis events: a qualitative description.
AB  - BACKGROUND: Patients experiencing severe mental illnesses (SMI) need continuing
      support and remain vulnerable in many domains. Crisis interventions and
      compulsory admissions are common, causing a huge burden on police, health
      workers, the community and patients. The aim of this retrospective case-file
      study is to determine profiles of SMI-patients and their pathways through care
      among those experiencing multiple public crisis events. METHODS: Data from a
      larger study of 323 SMI-patients in Amsterdam were used. These data were linked
      to data of the public mental health care (PMHC) in order to identify persons that
      experienced crisis interventions (CI's) between January 2004 and November 2012.
      The cut-off point for inclusion in the study population was set on three CI's,
      resulting in a group of 47 SMI-patients. PMHC and mental health care (MHC) data
      were linked in order to identify profiles in patterns of care. Qualitative
      content analysis was used to gather and analyze chronological timelines. RESULTS:
      Three profiles were identified: SMI-patients with CI's during continuous MHC, SMI
      patients with CI's after discharge and SMI-patients with CI's during unstable
      MHC. For each profile events prior to, during and after a CI were identified.
      CONCLUSIONS: PMHC and MHC can possibly identify cases with a high risk of CI's
      and predict these events based on the results of this study. CI's seem inevitable
      for a group of SMI-patients in care but they do not only require acute
      psychiatric care. The collaboration between MHC, PMHC and police could be further
      developed in a quick and effective triage in order to tackle the complexity of
      problems of the SMI-patients.

PMID- 27036707
TI  - Flutamide induces alterations in the cell-cell junction ultrastructure and
      reduces the expression of Cx43 at the blood-testis barrier with no disturbance in
      the rat seminiferous tubule morphology.
AB  - BACKGROUND: Present study was designed to establish a causal connection between
      changes in the cell-cell junction protein expression at the blood-testis barrier
      and alterations in the adult rat testis histology following an anti-androgen
      flutamide exposure. Particular emphasis was placed on the basal ectoplasmic
      specialization (ES) in the seminiferous epithelium and expression of gap junction
      protein, connexin 43 (Cx43). METHODS: Flutamide (50 mg/kg body weight) was
      administered to male rats daily from 82 to 88 postnatal day. Testes from 90-day
      old control and flutamide-exposed rats were used for all analyses. Testis
      morphology was analyzed using light and electron microscopy. Gene and protein
      expressions were analyzed by real-time RT-PCR and Western blotting, respectively,
      protein distribution by immunohistochemistry, and steroid hormone concentrations
      by radioimmunoassay. RESULTS: Seminiferous epithelium of both groups of rats
      displayed normal histology without any loss of germ cells. In accord, no
      difference in the apoptosis and proliferation level was found between control and
      treated groups. As shown by examination of semi-thin and ultrathin sections, cell
      surface occupied by the basal ES connecting neighboring Sertoli cells and the
      number of gap and tight junctions coexisting with the basal ES were apparently
      reduced in flutamide-treated rats. Moreover, the appearance of unconventional
      circular ES suggests enhanced internalization and degradation of the basal ES.
      These changes were accompanied by decreased Cx43 and ZO-1 expression (p < 0.01)
      and a loss of linear distribution of these proteins at the region of the blood
      testis barrier. On the other hand, Cx43 expression in the interstitial tissue of
      flutamide-treated rats increased (p < 0.01), which could be associated with
      Leydig cell hypertrophy. Concomitantly, both intratesticular testosterone and
      estradiol concentrations were elevated (p < 0.01), but testosterone to estradiol
      ratio decreased significantly (p < 0.05) in flutamide-treated rats compared to
      the controls. CONCLUSIONS: Short-term treatment with flutamide applied to adult
      rats exerts its primary effect on the basal ES, coexisting junctional complexes
      and their constituent proteins Cx43 and ZO-1, without any apparent morphological
      alterations in the seminiferous epithelium. In the interstitial compartment,
      however, short-term exposure leads to both histological and functional changes of
      the Leydig cells.

PMID- 27036708
TI  - Emergence of a daptomycin-non-susceptible Enterococcus faecium strain that
      encodes mutations in DNA repair genes after high-dose daptomycin therapy.
AB  - BACKGROUND: An increasing number of reports have documented the emergence of
      daptomycin-nonsusceptible Enterococcus in patients during daptomycin therapy.
      Even though several mechanisms for daptomycin-nonsusceptibility have been
      suggested, the potential genetic mutations which might contribute to the
      daptomycin-nonsusceptibility are not fully understood. CASE PRESENTATION: We
      isolated a vancomycin-susceptible, daptomycin nonsusceptible Enterococcus faecium
      strain from a patient with acute lymphocytic leukemia who received high-dose
      daptomycin therapy for E. faecium endocarditis. Whole-genome sequencing analysis
      revealed mutations within genes encoding DNA repair proteins MutL and RecJ of the
      daptomycin-nonsusceptible Enterococcus strain which might have facilitated its
      emergence. CONCLUSIONS: We identified the mutations of DNA mismatch repair genes
      in a clinical isolate of daptomycin nonsusceptible E. faecium which emerged in
      spite of high-dose daptomycin therapy. The finding implicates the possible
      association of DNA repair mechanism and daptomycin resistance. Careful monitoring
      is necessary to avoid the emergence of daptomycin non-susceptible isolates of E.
      faecium and particularly in cases of long-term daptomycin use or in
      immunocompromised patients.

PMID- 27036709
TI  - Super-resolution microscopy reveals gamma-secretase at both sides of the neuronal
      synapse.
AB  - The transmembrane protein assembly gamma-secretase is a key protease in regulated
      intramembrane processing (RIP) of around 100 type-1 transmembrane proteins.
      Importantly, it has a pathological role in Alzheimer disease (AD) as it generates
      the neurotoxic amyloid beta-peptide from the amyloid precursor protein (APP).
      Studies on gamma-secretase location are therefore crucial both from a biological
      and a therapeutic perspective. Despite several years of efforts in many
      laboratories, it is not clear where in the neuron gamma-secretase exerts it's
      activities. Technical challenges include the fact that the active enzyme contains
      four protein components and that most subcellular compartments cannot be
      spatially resolved by traditional light microscopy. Here, we have used a powerful
      combination of the two nanoscopy techniques STORM and STED microscopy to
      visualize the location of gamma-secretase in neurons using an active-site
      specific probe, with a focus on the synapse. We show that gamma-secretase is
      present in both the pre-and postsynaptic compartments. We further show that the
      enzyme is enriched very close to the synaptic cleft in the postsynaptic membrane,
      as well as to NMDA receptors, demonstrating that gamma-secretase is present in
      the postsynaptic plasma membrane. Importantly, the expression of gamma-secretase
      increased in the pre- and postsynaptic compartments with the size of the synapse,
      suggesting a correlation between gamma-secretase activity and synapse maturation.
      Thus, our data shows the synaptic location with high precision in three
      dimensions and settles the long-lasting debate on the synaptic location of gamma
      secretase. 

PMID- 27036710
TI  - In vitro and in vivo reduction of post-prandial blood glucose levels by ethyl
      alcohol and water Zingiber mioga extracts through the inhibition of carbohydrate
      hydrolyzing enzymes.
AB  - BACKGROUND: Type 2 diabetes is a serious problem for developed and developing
      countries. Prevention of prediabetes progression to type 2 diabetes with the use
      of natural products appears to be a cost-effective solution. Zingiber mioga has
      been used as a traditional food in Asia. Recent research has reported the
      potential health benefits of Zingiber mioga, but the blood glucose reducing
      effect has not been yet evaluated. METHODS: In this study Zingiber mioga extracts
      (water and ethanol) were investigated for their anti-hyperglycemic and
      antioxidant potential using both in vitro and animal models. The in vitro study
      evaluated the total phenolic content, the oxygen radical absorbance capacity
      (ORAC) and the inhibitory effect against carbohydrate hydrolyzing enzymes
      (porcine pancreatic alpha-amylase and rat intestinal sucrase and maltase) of both
      Zingiber mioga extracts. Also, the extracts were evaluated for their in vivo post
      prandial blood glucose reducing effect using SD rat and db/db mice models.
      RESULTS: Our findings suggest that the ethanol extract of Zingiber mioga (ZME)
      exhibited the higher sucrase and maltase inhibitory activity (IC50, 3.50 and 3.13
      mg/mL) and moderate alpha-amylase inhibitory activity (IC50, >10 mg/mL).
      Additionally, ZME exhibited potent peroxyl radical scavenging linked antioxidant
      activity (0.53/TE 1 MUM). The in vivo study using SD rat and db/db mice models
      also showed that ZME reduces postprandial increases of blood glucose level after
      an oral administration of sucrose by possibly acting as an intestinal alpha
      glucosidase inhibitor (ZME 0.1 g/kg 55.61 +/- 13.24 mg/dL) CONCLUSION: The
      results indicate that Zingiber mioga extracts exhibited significant in vitro
      alpha-glucosidase inhibition and antioxidant activity. Additionally, the tested
      extracts demonstrated in vivo anti-hyperglycemic effects using SD rat and db/db
      mice models. Our findings provide a strong rationale for the further evaluation
      of Zingiber mioga for the potential to contribute as a useful dietary strategy to
      manage postprandial hyperglycemia.

PMID- 27036711
TI  - The impact of exercise-induced core body temperature elevations on coagulation
      responses.
AB  - OBJECTIVES: Exercise induces changes in haemostatic parameters and core body
      temperature (CBT). We aimed to assess whether exercise-induced elevations in CBT
      induce pro-thrombotic changes in a dose-dependent manner. DESIGN: Observational
      study. METHODS: CBT and haemostatic responses were measured in 62 participants of
      a 15-km road race at baseline and immediately after finishing. As haemostasis
      assays are routinely performed at 37 degrees C, we corrected the assay
      temperature for the individual's actual CBT at baseline and finish in a subgroup
      of n=25. RESULTS: All subjects (44+/-11 years, 69% male) completed the race at a
      speed of 12.1+/-1.8km/h. CBT increased significantly from 37.6+/-0.4 degrees C to
      39.4+/-0.8 degrees C (p<0.001). Post-exercise, haemostatic activity was
      increased, as expressed by accelerated thrombin generation and an attenuated
      plasmin response. Synchronizing assay temperature to the subjects' actual CBT
      resulted in additional differences and stronger acceleration of thrombin
      generation parameters. CONCLUSIONS: This study demonstrates that exercise induces
      a prothrombotic state, which might be partially dependent on the magnitude of the
      exercise-induced CBT rise. Synchronizing the assay temperature to approximate the
      subject's CBT is essential to obtain more accurate insight in the haemostatic
      balance during thermoregulatory challenging situations. Finally, this study shows
      that short-lasting exposure to a CBT of 41.2 degrees C does not result in
      clinical symptoms of severe coagulation. We therefore hypothesize that prolonged
      exposure to a high CBT or an individual-specific CBT threshold needs to be
      exceeded before derailment of the haemostatic balance occurs.

PMID- 27036713
TI  - The 21st-Century Trajectory for Global Health.

PMID- 27036712
TI  - The effect of session order on the physiological, neuromuscular, and endocrine
      responses to maximal speed and weight training sessions over a 24-h period.
AB  - OBJECTIVES: Athletes are often required to undertake multiple training sessions
      on the same day with these sessions needing to be sequenced correctly to allow
      the athlete to maximize the responses of each session. We examined the acute
      effect of strength and speed training sequence on neuromuscular, endocrine, and
      physiological responses over 24h. DESIGN: 15 academy rugby union players
      completed this randomized crossover study. METHODS: Players performed a weight
      training session followed 2h later by a speed training session (weights speed)
      and on a separate day reversed the order (speed weights). Countermovement jumps,
      perceived muscle soreness, and blood samples were collected immediately prior,
      immediately post, and 24h post-sessions one and two respectively. Jumps were
      analyzed for power, jump height, rate of force development, and velocity. Blood
      was analyzed for testosterone, cortisol, lactate and creatine kinase. RESULTS:
      There were no differences between countermovement jump variables at any of the
      post-training time points (p>0.05). Likewise, creatine kinase, testosterone,
      cortisol, and muscle soreness were unaffected by session order (p>0.05). However,
      10m sprint time was significantly faster (mean+/-standard deviation; speed
      weights 1.80+/-0.11s versus weights speed 1.76+/-0.08s; p>0.05) when speed was
      sequenced second. Lactate levels were significantly higher immediately post-speed
      sessions versus weight training sessions at both time points (p<0.05).
      CONCLUSIONS: The sequencing of strength and speed training does not affect the
      neuromuscular, endocrine, and physiological recovery over 24h. However, speed may
      be enhanced when performed as the second session.

PMID- 27036714
TI  - Building Trust: A Critical Component of Global Health.

PMID- 27036715
TI  - Global/Local: What Does It Mean for Global Health Educators and How Do We Do It?
AB  - BACKGROUND: There has been dramatic growth in the number of innovative university
      programs that focus on social justice and teach community-based strategies that
      are applicable both domestically in North America and internationally. These
      programs often are referred to as global/local and reflect an effort to link
      global health and campus community engagement efforts to acknowledge that a
      common set of transferable skills can be adapted to work with vulnerable
      populations wherever they may be. However, the concepts underlying global/local
      education are undertheorized and universities struggle to make the global/local
      link without a conceptual framework to guide them in this pursuit. OBJECTIVES:
      This study reports on the outcomes of a 2015 national meeting of 120 global
      health educators convened to discuss the concepts underlying global/local
      education, to share models of global/local programs, and to draft a preliminary
      list of critical elements of a meaningful and didactically sound global/local
      educational program. METHODS: A qualitative analysis was conducted of the
      discussions that took place at the national meeting. The analysis was supported
      by videorecordings made of full-group discussions. Results were categorized into
      a preliminary list of global/local program elements. Additionally, a synthesis
      was developed of critical issues raised at the meeting that warrant future
      discussion and study. FINDINGS: A preliminary list was developed of 7 program
      components that global health educators consider essential to categorize a
      program as global/local and to ensure that such a program includes specific
      critical elements. CONCLUSIONS: Interest is great among global health educators
      to understand and teach the conceptual link between learning on both the global
      and community levels. Emphasis on this link has high potential to unite the
      siloed fields of global health and domestic community public health and the
      institutions, funding options, and career pathways that flow from them. Future
      research should focus on implementation of global/local programming and
      evaluation of student learning and community health outcomes related to such
      programs.

PMID- 27036716
TI  - Evaluation and Support Mechanisms of an Emerging University-wide Global Health
      Training Program.
AB  - BACKGROUND: Global health education is in high demand in the United States,
      across the continuum of learning, and field experiences are an essential part of
      this education. However, evaluations of these programs are limited. OBJECTIVES:
      The aim of this study was to evaluate a field placement program at Johns Hopkins
      University, in Baltimore, Maryland, to understand how to better support student
      training overseas and faculty mentorship. METHODS: We used qualitative and
      quantitative methods to gather data from program reporting requirements (152
      student surveys and 46 experiential narrative essays), followed by 17
      semistructured interviews, and 2 focus groups. Data were analyzed through manual
      coding and a socioecological model served as an analytical and a synthesizing
      framework. FINDINGS: A series of factors influence the participants' experience
      in overseas placements spanning across 4 aggregate levels, from individual to
      societal, including opportunity for professional advancement, independence,
      loneliness and illness, mentorship quality, funding, institutional partnership
      building, opportunity for public health contribution, and for development of
      cultural competency. Faculty and students thought that the program was beneficial
      to the learning experience, particularly for its contribution to experiential
      knowledge of a low- and middle-income country setting and for developing cross
      cultural relationships. Communication and scope of work were 2 areas in which
      students and faculty members often had different expectations and many students
      emerged having cultivated different skills than they or their mentor initially
      expected. Students found the experience useful for both their academic and
      professional careers and faculty members saw mentorship, one of their
      professional responsibilities, emerge. CONCLUSIONS: Many socioecological factors
      influence an overseas field experience, which in turn produces important effects
      on students' career choices, and faculty members appreciate the opportunity to
      serve as mentors. The most vital support mechanisms suggested for faculty and
      students included available funding, clear preparation, and communication
      facilitation across the experiential continuum.

PMID- 27036717
TI  - Global Health Diplomacy, "San Francisco Values," and HIV/AIDS: From the Local to
      the Global.
AB  - BACKGROUND: San Francisco has a distinguished history as a cosmopolitan,
      progressive, and international city, including extensive associations with global
      health. These circumstances have contributed to new, interdisciplinary
      scholarship in the field of global health diplomacy (GHD). In the present review,
      we describe the evolution and history of GHD at the practical and theoretical
      levels within the San Francisco medical community, trace related associations
      between the local and the global, and propose a range of potential opportunities
      for further development of this dynamic field. METHODS: We provide a historical
      overview of the development of the "San Francisco Model" of collaborative,
      community-owned HIV/AIDS treatment and care programs as pioneered under the "Ward
      86" paradigm of the 1980s. We traced the expansion and evolution of this model to
      the national level under the Ryan White Care Act, and internationally via the
      President's Emergency Plan for AIDS Relief. In parallel, we describe the
      evolution of global health diplomacy practices, from the local to the global,
      including the integration of GHD principles into intervention design to ensure
      social, political, and cultural acceptability and sensitivity. RESULTS: Global
      health programs, as informed by lessons learned from the San Francisco Model, are
      increasingly aligned with diplomatic principles and practices. This awareness has
      aided implementation, allowed policymakers to pursue related and progressive
      social and humanitarian issues in conjunction with medical responses, and
      elevated global health to the realm of "high politics." CONCLUSIONS: In the 21st
      century, the integration between diplomatic, medical, and global health practices
      will continue under "smart global health" and GHD paradigms. These approaches
      will enhance intervention cost-effectiveness by addressing and optimizing, in
      tandem with each other, a wide range of (health and non-health) foreign policy,
      diplomatic, security, and economic priorities in a synergistic manner--without
      sacrificing health outcomes.

PMID- 27036718
TI  - A New Master's Degree in Global Health: Reflections on a 5-year Experience.
AB  - BACKGROUND: The University of California-San Francisco's (UCSF) Master of Science
      (MS) degree in global health sciences, a 1-year degree program started in 2008,
      is the first accredited master's degree in global health in the country.
      OBJECTIVE: The aim of this study was to review the genesis and structure of the
      MS degree program, and describe its progress over its first 5 years. METHODS: We
      reviewed the program's teaching methods, academic curriculum, course evaluations,
      and backgrounds and outcomes of the first 127 graduates. Student opinions were
      gathered from anonymous course evaluations. Student outcome data and graduates'
      perspectives were gathered through a voluntary, anonymous, online survey. We
      reflect on student demand, program strengths and weaknesses, and future academic
      directions. FINDINGS: The program's structure arose from three learning
      objectives identified by the Curriculum Committee: a multidisciplinary approach
      to the foundations of global health, an emphasis on research design and methods,
      and an application of theory to international fieldwork. The resulting broad
      curriculum has attracted students of diverse backgrounds, which has enriched
      classroom discussions. Over the first 5 years, the program revised its fieldwork
      project criteria to allow more flexibility in design, leading to a higher rate of
      publication and enabling students to graduate with an academic portfolio.
      Students have reported that the high faculty-to-student ratio has fostered strong
      mentorship relationships; this is vital as 66% of graduates work in academics.
      Graduates have reflected that group work in the program appropriately prepared
      them for their work environment. The program's experience has guided its response
      to: pressure to focus on medical aspects of global health; students' needs for
      career skill-building; financial challenges; and trends toward online didactics.
      CONCLUSIONS: The recent surge in interest in global health careers has created
      demand for academic programs. UCSF has designed the MS degree program to balance
      breadth and depth of learning in a multidisciplinary curriculum, and combine
      career preparation and theoretical learning in a one-year academic degree. The
      challenges of balancing breadth and depth of learning in a multidisciplinary
      program, and combining career preparation and theoretical learning in a one-year
      academic degree, have informed UCSF's MS program design.

PMID- 27036719
TI  - Training Young Russian Physicians in Uganda: A Unique Program for Introducing
      Global Health Education in Russia.
AB  - BACKGROUND: Global health is a new concept in Russia. There has been an ongoing
      academic collaboration between the Yale School of Medicine in the United States
      and Makerere University College of Health Sciences in Uganda since 2010, and the
      US Western Connecticut Health Network/University of Vermont College of Medicine
      since 2012, to introduce global health concepts to Kazan State Medical University
      (KSMU) in Russia. The purpose was to educate Russian physicians and medical
      trainees about the practice of clinical medicine and medical education, as well
      as the general practice of global health in culturally diverse, resource-limited
      settings. OBJECTIVES: The aim of this study was to evaluate the initial outcomes
      of this multi-institutional partnership and to assess the impact of the global
      health elective on the participants and on KSMU. METHODS: Participants were
      selected to attend a 6-week elective in global health at Mulago Hospital in
      Kampala, Uganda. The elective consisted of clinical experience, education about
      Uganda's common diseases, and region-specific sociocultural classes. It included
      a predeparture orientation and, upon return, completion of a standard
      questionnaire to assess the program's impact. RESULTS: Since 2010, there have
      been 20 KSMU members (4 medical students, 4 interns, 9 residents, 2 fellows, and
      1 faculty member) who have participated in the program. As a result of the
      elective, the participants reported increased knowledge of tropical medicine
      (70%) and HIV/AIDS (75%), and 95% reported increased cultural sensitivity and
      desire to work with the underserved. The majority noted a very positive impact of
      their careers (90%) and personal life (80%). KSMU established the first
      successful collaborative program in global health education in Russia, leading to
      the integration of tropical medicine and global health courses in medical school
      curriculum. CONCLUSION: This elective has proven highly effective in introducing
      the concept of global health to faculty, fellows, residents, and medical students
      at KSMU. It trained these participants to address the challenges faced by
      physicians in culturally diverse and resource-limited countries.

PMID- 27036720
TI  - Giving Voice to the Experiences of Rwandan Women With Urogenital Fistula.
AB  - BACKGROUND: Urogenital fistula is a debilitating condition that women can develop
      following obstructed labor. The primary objective of this study was to reveal
      illness narratives of Rwandan women with urogenital fistula to appreciate their
      unique experiences. The secondary aim was to identify common themes that emerged
      when women discussed their experiences living with fistula. METHODS: Women
      presenting for urogenital fistula repair at Kibagabaga Hospital were asked to
      participate in the study. Eleven participants were asked questions designed to
      elicit their understanding of their condition and the social and emotional
      consequences of their fistula. All interviews were anonymous. Transcribed
      interviews were examined for relative themes to categorize responses into larger
      domains. FINDINGS: Common themes were identified from the interviews on topics of
      what barriers existed to having a successful delivery, the socioeconomic and
      psychosocial consequences of developing a fistula, and each woman's understanding
      of her fistula. Excerpts from patients' illness narratives illustrated these
      themes. CONCLUSIONS: These narratives can be used to appreciate the variations in
      each woman's understanding of her medical condition and the changes that occurred
      in her life as a result of her fistula. Through patients' narratives, physicians
      can improve their appreciation of cultural differences to design targeted
      educational and preventive interventions.

PMID- 27036721
TI  - Treatment and Prevention of Pandemic H1N1 Influenza.
AB  - BACKGROUND: Swine influenza is a respiratory infection common to pigs worldwide
      caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1,
      H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness
      in humans and affect persons of all age groups. People in close contact with
      swine are at especially high risk. Until recently, epidemiological study of
      influenza was limited to resource-rich countries. The World Health Organization
      declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported
      30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased
      substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine
      influenza were reported with 774 deaths. METHODS: The Centers for Disease Control
      and Prevention recommend real-time polymerase chain reaction as the method of
      choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical
      treatment of swine influenza and can make the illness milder and enable the
      patient to feel better faster. FINDINGS: Antiviral drugs are most effective when
      they are started within the first 48 hours after the clinical signs begin,
      although they also may be used in severe or high-risk cases first seen after this
      time. The Centers for Disease Control and Prevention recommends use of
      oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline).
      CONCLUSION: Prevention of swine influenza has 3 components: prevention in swine,
      prevention of transmission to humans, and prevention of its spread among humans.
      Because of limited treatment options, high risk for secondary infection, and
      frequent need for intensive care of individuals with H1N1 pneumonia,
      environmental control, including vaccination of high-risk populations and public
      education are critical to control of swine influenza out breaks.

PMID- 27036722
TI  - Knowledge, Attitude, and Practices Regarding Vector-borne Diseases in Western
      Jamaica.
AB  - BACKGROUND: Outbreaks of vector-borne diseases (VBDs) such as dengue and malaria
      can overwhelm health systems in resource-poor countries. Environmental management
      strategies that reduce or eliminate vector breeding sites combined with improved
      personal prevention strategies can help to significantly reduce transmission of
      these infections. OBJECTIVE: The aim of this study was to assess the knowledge,
      attitudes, and practices (KAPs) of residents in western Jamaica regarding control
      of mosquito vectors and protection from mosquito bites. METHODS: A cross
      sectional study was conducted between May and August 2010 among patients or
      family members of patients waiting to be seen at hospitals in western Jamaica.
      Participants completed an interviewer-administered questionnaire on
      sociodemographic factors and KAPs regarding VBDs. KAP scores were calculated and
      categorized as high or low based on the number of correct or positive responses.
      Logistic regression analyses were conducted to identify predictors of KAP and
      linear regression analysis conducted to determine if knowledge and attitude
      scores predicted practice scores. FINDINGS: In all, 361 (85 men and 276 women)
      people participated in the study. Most participants (87%) scored low on knowledge
      and practice items (78%). Conversely, 78% scored high on attitude items. By
      multivariate logistic regression, housewives were 82% less likely than laborers
      to have high attitude scores; homeowners were 65% less likely than renters to
      have high attitude scores. Participants from households with 1 to 2 children were
      3.4 times more likely to have high attitude scores compared with those from
      households with no children. Participants from households with at least 5 people
      were 65% less likely than those from households with fewer than 5 people to have
      high practice scores. By multivariable linear regression knowledge and attitude
      scores were significant predictors of practice score. CONCLUSION: The study
      revealed poor knowledge of VBDs and poor prevention practices among participants.
      It identified specific groups that can be targeted with vector control and
      personal protection interventions to decrease transmission of the infections.

PMID- 27036723
TI  - A Cross-sectional Study on Hepatitis B Vaccination Status and Post-exposure
      Prophylaxis Practices Among Health Care Workers in Teaching Hospitals of
      Mangalore.
AB  - BACKGROUND: Health care workers (HCWs) are at high risk for acquiring hepatitis B
      virus infection because of needle stick injury (NSI) and occupational exposures
      to potentially infectious bodily fluids. Hepatitis B vaccination confers
      protection against the infection. Very little information is available in India
      about current vaccination status and postexposure prophylaxis (PEP) practices
      among HCWs. OBJECTIVES: This study had 2 objectives. The first was to
      characterize current vaccination coverage among HCWs, and the second was to
      define PEP practices among HCWs after NSI and exposures to potentially infectious
      bodily fluids. METHODS: A questionnaire-based, cross-sectional study was
      conducted in hospitals attached to Kasturba Medical College, Mangalore. We
      selected 297 individuals. A pretested, semistructured questionnaire was devised
      to collect information from study participants. After obtaining permission from
      the Institutional Ethics Committee, data were collected by interviewing HCWs in
      the hospitals. Analysis was done using SPSS. FINDINGS: Nearly all (93.8%) of the
      HCWs surveyed had taken 1 dose of hepatitis B vaccine. However, only 57.1%
      completed the primary series of 3 doses and only 26.4% had taken 1 or more
      booster doses. Of the HCWs questioned, 24.8% had experienced NSIs, exposure to
      potentially infectious bodily fluids, or both. Local measures were the PEP
      practices most commonly used (85.5%) by the HCWs. CONCLUSION: The present study
      demonstrated that there is a need in Mangalore to improve the vaccination
      coverage and train HCWs in appropriate PEP practices. This will protect the
      workers from acquiring hepatitis B infection.

PMID- 27036724
TI  - Innate Cellular Immunity in Newly Diagnosed Pulmonary Tuberculosis Patients and
      During Chemotherapy.
AB  - BACKGROUND: Leukocyte migration (LM) and intracellular killing aspects of the
      innate immune response play important roles in protection against and containment
      and cure of Mycobacterium tuberculosis infection, and thus may be exploited as
      immunotherapeutic targets to improve the management and treatment outcomes of
      patients with tuberculosis (TB). OBJECTIVES: The aim of this study was to assess
      LM and mediators of intracellular killing in patients with TB at the time of
      diagnosis and during anti-TB chemotherapy and compare them with apparently
      healthy controls. METHODS: We recruited 24 patients who were newly diagnosed with
      pulmonary TB and 20 apparently healthy individuals. Blood was drawn from patients
      with TB at the time of diagnosis, and after 2, 4, and 6 months of anti-TB
      chemotherapy and control. In vitro percentage LM (%LM) upon stimulation with
      Bacillus Calmette-Guerin vaccine, percentage nitroblue tetrazolium (%NBT)
      reduction, plasma concentrations of hydrogen peroxide (H2O2), and nitric oxide
      (NO) were assessed in both groups. FINDINGS: Percentage NBT was significantly
      reduced in patients with TB at 2 months of anti-TB chemotherapy compared with
      patients at diagnosis and in healthy controls, whereas %LM was significantly
      increased in patients at 4 months of anti-TB chemotherapy compared with patients
      at diagnosis and controls. Mean plasma H2O2 and NO were significantly reduced in
      patients at diagnosis and throughout the period of anti-TB chemotherapy compared
      with the control group. Significant decreases were demonstrated in mean plasma
      H2O2 and NO in patients at 2 and 4 months of anti-TB chemotherapy, respectively,
      compared with patients at diagnosis. There was significant positive correlation
      between %NBT with plasma H2O2 and NO, but %LM was negatively correlated with
      plasma H2O2 in this group. CONCLUSION: The intracellular killing aspect of innate
      cellular immunity is deficient in patients with TB, especially 2 to 4 months
      after commencement of treatment. Therefore, measures (eg, arginine
      supplementation) to improve intracellular killing in these patients is advocated.
      Moreover, %LM assay with Bacillus Calmette-Guerin vaccine as an antigen may be
      used to differentiate those newly diagnosed patients from those on anti-TB
      chemotherapy.

PMID- 27036725
TI  - Global Variation of Human Papillomavirus Genotypes and Selected Genes Involved in
      Cervical Malignancies.
AB  - BACKGROUND: Carcinoma of the cervix is ranked second among the top 5 cancers
      affecting women globally. Parallel to other cancers, it is also a complex disease
      involving numerous factors such as human papillomavirus (HPV) infection followed
      by the activity of oncogenes and environmental factors. The incidence rate of the
      disease remains high in developing countries due to lack of awareness, followed
      by mass screening programs, various socioeconomic issues, and low usage of
      preventive vaccines. Over the past 3 decades, extensive research has taken place
      in cervical malignancy to elucidate the role of host genes in the pathogenesis of
      the disease, yet it remains one of the most prevalent diseases. It is imperative
      that recent genome-wide techniques be used to determine whether carcinogenesis of
      oncogenes is associated with cervical cancer at the molecular level and to
      translate that knowledge into developing diagnostic and therapeutic tools.
      OBJECTIVE: The aim of this study was to discuss HPV predominance with their
      genotype distribution worldwide, and in India, as well as to discuss the newly
      identified oncogenes related to cervical cancer in current scenario. FINDINGS:
      Using data from various databases and robust technologies, oncogenes associated
      with cervical malignancies were identified and are explained in concise manner.
      CONCLUSION: Due to the advent of recent technologies, new candidate genes are
      explored and can be used as precise biomarkers for screening and developing drug
      targets.

PMID- 27036726
TI  - Improved Domestic Funding Enhances the Sustainability of HIV/AIDS Response in
      Nigeria.

PMID- 27036727
TI  - Serum Levels of Cytokines and IgE in Helminth-Infected Nigerian Pregnant Women
      and Children.
AB  - BACKGROUND: Helminth infection is an important health challenge. Because of
      modulation of the immune response toward T-helper 2 (Th2) cells, the immunologic
      interplay that manifest during the coexistence of helminth infection with other
      conditions is still poorly understood. OBJECTIVE: This study determined the
      pattern of alteration in selected cytokines and immunoglobulin E (IgE) in
      pregnant women, preschool aged children, and school-aged children with helminth
      infection compared with uninfected groups. METHODS: Seventeen pregnant women, 42
      preschool-aged children, and 60 school-aged children with helminth infection (HI)
      were recruited into this study. They were matched with 21 pregnant women, 42
      preschool-aged children, and 50 school-aged children without helminth infection
      (HN) who served as controls. Venous blood samples were collected from each
      participant and analyzed for serum levels of tumor necrosis factor alpha (TNF
      alpha), interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6), and
      IgE. Statistical analysis was done using the Student t test, and P < .05 was
      considered as statistically significant. FINDINGS: Only serum level of IgE was
      significantly elevated in HI pregnant women compared with HN pregnant women. In
      HI preschool- and school-aged children, serum levels of IL-8, IL-6, and IgE were
      significantly elevated compared with HN children. However, preschool- and school
      aged children with HI had similar levels of serum TNF-alpha and IL-10 compared
      with their corresponding HN groups. CONCLUSIONS: It could be concluded that
      altered cytokines expression in children and pregnant women with helminth
      infection might have some implications on need for deworming programs to improve
      pregnancy outcomes and vaccine responses.

PMID- 27036728
TI  - Spatiotemporal Anopheles Population Dynamics, Response to Climatic Conditions:
      The Case of Chabahar, South Baluchistan, Iran.
AB  - BACKGROUND: An understanding of the factors that affect the abundance of
      Anopheline species provides an opportunity to better understand the dynamics of
      malaria transmission in different regions. Chabahar, located south east of Iran,
      is the most malarious region in the country. OBJECTIVE: The main aim of this
      study was to quantify the spatiotemporal Anopheles population dynamics, response
      to climatic conditions in Chabahar. METHODS: Satellite-based and land-based
      climatic data were used as explanatory variables. Monthly caught mosquitoes in 6
      village sites of Chabahar were used as dependent variable. The spatiotemporal
      associations were first investigated by inspection of scatter plots and single
      variable regression analysis. A multivariate linear regression model was
      developed to reveal the association between environmental variables and the
      monthly mosquito abundance at a 95% confidence level (P <= 0.5). FINDINGS:
      Results indicated that Anopheles mosquitoes can be found all year in Chabahar
      with 2 significant seasonal peaks from March to June (primary peak) and September
      to November (secondary peak). Results of the present study showed that 0.77 of
      yearly mosquito abundance emerges in the thermal range of 24 degrees C to 30
      degrees C and the humidity range of 0.70 to 0.80 in Chabahar. CONCLUSION:
      According to the developed multivariate linear model, 0.88 of temporal variance
      of mosquito abundance, nighttime land surface temperature, and relative humidity
      of 15 Universal Time Coordinated (18.30 Iran) are the main drivers of mosquito
      population dynamics in Chabahar.

PMID- 27036729
TI  - Serum Micronutrients in Helminth-infected Pregnant Women and Children:
      Suggestions for Differential Supplementation During Anti-helminthic Treatment.
AB  - BACKGROUND: The prevalence of helminth infection, which is known to affect
      nutritional status of the host, varies with age. The complex interplay between
      ages, nutrient requirements, and infection necessitated the need to recommend
      micronutrient supplementation during helminth infection among different age
      groups. OBJECTIVE: The aim of this study was to determine the pattern of
      alteration in selected micronutrients in pregnant women and preschool- and school
      aged children with helminth infection. METHODS: We screened 245 pregnant women
      and 349 children for helminth infection. Of these, 17 (6.9%) pregnant women and
      102 (29.2%) children (42 preschool- and 60 school-aged) had helminth infection.
      Only Ascaris lumbricoides was found in pregnant women, whereas the children had A
      lumbricoides, hookworm, Fasciola hepatica, and Trichuris trichiura infections.
      The helminth-infected (HI) pregnant women, preschool-aged children, and school
      aged children were matched with helminth-negative (HN) pregnant women (n = 21),
      preschool-aged children (n = 42), and school-aged children (n = 50) who served as
      controls. Venous blood samples were obtained and analyzed for iron (Fe), zinc
      (Zn), selenium (Se), and vitamins A and C. Statistical analysis was done using
      Student's t test, and P < 0.05 was considered statistically significant.
      FINDINGS: Serum levels of Fe, Zn, and Se were significantly lower in HI pregnant
      women than HN pregnant women. In preschool-aged children, serum levels of Fe, Zn,
      and vitamin A were significantly lower in the HI than in the HN group. Similarly,
      serum levels of Zn and vitamin A were significantly lower in HI school-aged
      children than in the HN group. However, serum levels of Se were significantly
      higher in HI children (both age groups) than in the corresponding HN group.
      CONCLUSION: Helminth infection alters different types of micronutrients in
      children and pregnant women. Results from the present study therefore suggest
      monitoring Fe, Zn, or vitamin A supplementation with an anti-helminthic regimen.

PMID- 27036730
TI  - Alcohol-Attributable Fraction in Liver Disease: Does GDP Per Capita Matter?
AB  - BACKGROUND: The alcohol-attributable fraction (AAF) quantifies alcohol's disease
      burden. Alcoholic liver disease (ALD) is influenced by alcohol consumption per
      capita, duration, gender, ethnicity, and other comorbidities. In this study, we
      investigated the association between AAF/alcohol-related liver mortality and
      alcohol consumption per capita, while stratifying to per-capita gross domestic
      product (GDP). METHODS: Data obtained from the World Health Organization and
      World Bank for both genders on AAF on liver disease, per-capita alcohol
      consumption (L/y), and per-capita GDP (USD/y) were used to conduct a cross
      sectional study. Countries were classified as "high-income" and "very low income"
      if their respective per-capita GDP was greater than $30,000 or less than $1,000.
      Differences in total alcohol consumption per capita and AAF were calculated using
      a 2-sample t test. Scatterplots were generated to supplement the Pearson
      correlation coefficients, and F test was conducted to assess for differences in
      variance of ALD between high-income and very low income countries. FINDINGS:
      Twenty-six and 27 countries met the criteria for high-income and very low income
      countries, respectively. Alcohol consumption per capita was higher in high-income
      countries. AAF and alcohol consumption per capita for both genders in high-income
      and very low income countries had a positive correlation. The F test yielded an F
      value of 1.44 with P = .357. No statistically significant correlation was found
      among alcohol types and AAF. Significantly higher mortality from ALD was found in
      very low income countries relative to high-income countries. DISCUSSION: Previous
      studies had noted a decreased AAF in low-income countries as compared to higher
      income countries. However, the non-statistically significant difference between
      AAF variances of low-income and high-income countries was found by this study. A
      possible explanation is that both high-income and low-income populations will
      consume sufficient amount of alcohol, irrespective of its type, enough to weigh
      into equivalent AAF. CONCLUSIONS: No significant difference of AAF variance was
      found between high-income and very low income countries relating to sex-specific
      alcohol consumption per capita. Alcohol consumption per capita was greater in
      high-income countries. Type of preferred alcohol did not correlate with AAF. ALD
      related mortality was less in high-income countries as a result of better
      developed healthcare systems. ALD remains a significant burden globally,
      requiring prevention from socioeconomic, medical, and political realms.

PMID- 27036731
TI  - A Pilot Initiative to Deliver Community-based Psychiatric Services in Rural Haiti
      After the 2010 Earthquake.
AB  - BACKGROUND: Worldwide, there is a gap between the burden of mental distress and
      disorder and access to mental health care. This gap is particularly large in low-
      and middle-income countries (LMICs). After the 2010 earthquake in Haiti, the
      international health care organizations Partners in Health and Zanmi Lasante
      worked to expand local mental health services in rural Haiti. OBJECTIVE: The aims
      of this study are to describe clinical characteristics of the patients served
      during a pilot project to deliver community-based psychiatric services in rural
      Haiti and to show how this experience complements the Mental Health Gap Action
      Programme ("mhGAP"), a tool developed by the World Health Organization to support
      mental health care delivery by nonspecialists in LMICs. METHODS: The pilot was
      conducted in March 2011. A visiting psychiatrist traveled to rural Haiti and
      paired with local clinicians to evaluate patients and to support quality
      improvement practices in psychiatric care. Patients received a standard
      neuropsychiatric evaluation. mhGAP was an important clinical reference. To assess
      the experience, we conducted a retrospective chart review of outpatient
      encounters. FINDINGS: Sixty-five patients presented with a wide range of common
      psychiatric, neurologic, and general medical conditions. Forty-nine of these
      patients (75%) reported primary problems subsumed by an mhGAP module. Fifteen
      patients (23%) reported headache as their chief complain, a condition that is not
      currently covered by mhGAP. Surprisingly, only 3 patients (5%), reported
      earthquake-related distress. CONCLUSIONS: Our clinical data reinforce the need
      for provision of standard psychiatric and neurologic services in LMICs. Such
      services ought to accompany interventions targeted specifically at disaster
      related problems. Clinical situations falling outside existing mhGAP modules
      inspired the development of supplemental treatment protocols. These observations
      informed coordinated efforts at Zanmi Lasante to build a sustainable, integrated
      mental health system in Haiti that may be relevant to other resource-limited
      settings.

PMID- 27036733
TI  - Free Continuing Professional Development Resources for Low-Resource Settings.

PMID- 27036732
TI  - Lessons Learned from Implementing a Rapid Test of a Technology Device in a
      Tertiary Hospital in Uganda.
AB  - BACKGROUND: Many African hospitals participate in technology research studies
      that take many months or years. Fewer sites have experience with rapid studies,
      conducted over a period of weeks. Such studies can benefit the institution and
      its patients in the short term, and in the long term can help prepare the
      institution for adopting the new technology. OBJECTIVES: We conducted a rapid
      validation study of consumer fitness device at Mulago National Referral and
      Teaching Hospital in Kampala, Uganda. In doing so, we captured valuable lessons
      about how to conduct a rapid study that will be useful to future researchers
      conducting similar fast-paced studies. METHODS: We conducted a descriptive study
      of a convenience sample of 57 patients. Patients who volunteered wore a fitness
      wristband device. Study staff collected vital signs using standard approaches.
      FINDINGS: Our findings were as follows: (1) effective partnership by local
      experts can ensure success; (2) a PI with experience working with the hospital
      ethics committee is essential to a rapid study; (3) reassurance that the study
      design benefits patients and the institution can help speed approval; (4) conduct
      detailed assessment of patient population in advance; (5) allow sufficient time
      for logistics arrangements; (6) quickly pivot the approach as needed, consistent
      with the protocol; (7) conduct data quality review on every shift; (8) conduct a
      supplies inventory at the end of each shift; (9) make rapid decisions about
      hiring and discontinuing study staff; (10) implement a patient location protocol
      at the start of the study; and (11) ensure availability of study staff
      refreshments in the study room. CONCLUSION: A rapid study of innovative
      technology can be successful at a hospital in a resource-limited setting.

PMID- 27036734
TI  - Identification of the novel activity-driven interaction between synaptotagmin 1
      and presenilin 1 links calcium, synapse, and amyloid beta.
AB  - BACKGROUND: Synaptic loss strongly correlates with memory deterioration. Local
      accumulation of amyloid beta (Abeta) peptide, and neurotoxic Abeta42 in
      particular, due to abnormal neuronal activity may underlie synaptic dysfunction,
      neurodegeneration, and memory impairments. To gain an insight into molecular
      events underlying neuronal activity-regulated Abeta production at the synapse, we
      explored functional outcomes of the newly discovered calcium-dependent
      interaction between Alzheimer's disease-associated presenilin 1 (PS1)/gamma
      secretase and synaptic vesicle proteins. RESULTS: Mass spectrometry screen of
      mouse brain lysates identified synaptotagmin 1 (Syt1) as a novel synapse-specific
      PS1-binding partner that shows Ca(2+)-dependent PS1 binding profiles in vitro and
      in vivo. We found that Abeta level, and more critically, conformation of the PS1
      and the Abeta42/40 ratio, are affected by Syt1 overexpression or knockdown,
      indicating that Syt1 and its interaction with PS1 might regulate Abeta production
      at the synapse. Moreover, beta-secretase 1 (BACE1) stability, beta- and gamma
      secretase activity, as well as intracellular compartmentalization of PS1 and
      BACE1, but not of amyloid precursor protein (APP), nicastrin (Nct), presenilin
      enhancer 2 (Pen-2), or synaptophysin (Syp) were altered in the absence of Syt1,
      suggesting a selective effect of Syt1 on PS1 and BACE1 trafficking. CONCLUSIONS:
      Our findings identify Syt1 as a novel Ca(2+)-sensitive PS1 modulator that could
      regulate synaptic Abeta, opening avenues for novel and selective synapse
      targeting therapeutic strategies.

PMID- 27036735
TI  - Impact of thrombus aspiration during ST-Elevation Myocardial Infarction: a six
      month composite endpoint and risk of stroke analyses of the TASTE trial.
AB  - BACKGROUND: Routine thrombus aspiration during primary percutaneous coronary
      intervention (PCI) in ST-elevation myocardial infarction (STEMI) did not reduce
      the primary composite endpoint in the "A Randomised Trial of Routine Aspiration
      ThrOmbecTomy With PCI Versus PCI ALone in Patients With STEMI Undergoing Primary
      PCI" (TOTAL) trial. We aimed to analyse a similar endpoint in "The Thrombus
      Aspiration in ST-Elevation myocardial infarction in Scandinavia" (TASTE) trial up
      to 180 days. METHODS: In TASTE, 7244 patients with STEMI were randomised to
      thrombus aspiration followed by PCI or to PCI alone. We analysed the quadruple
      composite endpoint of cardiovascular death, cardiogenic shock, rehospitalisation
      for myocardial infarction, or new hospitalisation for heart failure. Furthermore,
      an extended net-benefit composite endpoint including stent thrombosis, target
      vessel revascularization or stroke within 180 days was analysed. RESULTS: The
      primary quadruple composite endpoint occurred in 8.7 % (316 of 3621) in the
      thrombus aspiration group compared to 9.3 % (338 of 3623) in the PCI alone group
      (hazard ratio (HR), 0.93; 95 % confidence interval (CI); 0.80 - 1.09, P = 0.36)
      and the extended net-benefit composite endpoint in 12.0 % (436) vs. 13.2 % (479)
      (HR, 0.90; 95 % CI; 0.79 - 1.03, P = 0.12). Stroke within 30 days occurred in 0.7
      % (27) vs. 0.7 % (24) (HR, 0.89; 95 % CI; 0.51-1.54, P = 0.68). CONCLUSIONS: A
      large and an extended composite endpoint analysis from the TASTE trial did not
      demonstrate any clinical benefit of routine thrombus aspiration during PCI in
      patients with STEMI. There was no evidence of an increased risk of stroke with
      thrombus aspiration.

PMID- 27036736
TI  - CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10
      Producing Regulatory T Cells.
AB  - Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney
      DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of
      the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We
      studied the role of CD103+ DCs in cGN using several lines of genetically modified
      mice that allowed us to reduce the number of these cells. In all lines, we
      detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which
      protect against cGN. Mice lacking the transcription factor Batf3 had a more
      profound reduction of CD103+ DCs and Tregs than did the other lines used, and
      showed the most profound aggravation of cGN. The conditional reduction of CD103+
      DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice
      to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+
      DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3-/-
      mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as
      well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and
      Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of
      CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs
      caused cocultured T cells to differentiate into Tregs and produced the chemokine
      CCL20, which is known to attract Tregs into the kidney. Our findings show that
      CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing
      proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality
      might be advantageous in cGN.

PMID- 27036737
TI  - Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics.
AB  - In glomerular disease, podocyte injury results in a dramatic change in cell
      morphology known as foot process effacement. Remodeling of the actin cytoskeleton
      through the activity of small GTPases was identified as a key mechanism in
      effacement, with increased membrane activity and motility in vitro However,
      whether podocytes are stationary or actively moving cells in vivo remains
      debated. Using intravital and kidney slice two-photon imaging of the three
      dimensional structure of mouse podocytes, we found that uninjured podocytes
      remained nonmotile and maintained a canopy-shaped structure over time. On
      expression of constitutively active Rac1, however, podocytes changed shape by
      retracting processes and clearly exhibited domains of increased membrane
      activity. Constitutive activation of Rac1 also led to podocyte detachment from
      the glomerular basement membrane, and we detected detached podocytes crawling on
      the surface of the tubular epithelium and occasionally, in contact with
      peritubular capillaries. Podocyte membrane activity also increased in the
      inflammatory environment of immune complex-mediated GN. Our results provide
      evidence that podocytes transition from a static to a dynamic state in vivo,
      shedding new light on mechanisms in foot process effacement.

PMID- 27036738
TI  - Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates
      with Calcium Nephrolithiasis in Patients.
AB  - Hypercalciuria is a major risk factor for nephrolithiasis. We previously reported
      that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal
      calcium channel TRPV5. This channel is crucial for calcium reabsorption in the
      distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1
      (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease,
      the same disease caused by UMOD mutations. Because of the similarities between
      UMOD and MUC1 regarding associated disease phenotype, protein structure, and
      function as a cellular barrier, we examined whether urinary MUC1 also enhances
      TRPV5 channel activity and protects against nephrolithiasis. We established a
      semiquantitative assay for detecting MUC1 in human urine and found that, compared
      with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had
      significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in
      the thick ascending limb, DCT, and collecting duct. Applying whole-cell patch
      clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1
      increased TRPV5 activity by impairing dynamin-2- and caveolin-1-mediated
      endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction
      between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan
      deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs)
      that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA
      prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking
      VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a
      lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5
      endocytosis and increases urinary calcium reabsorption.

PMID- 27036740
TI  - The 25th SEM Congress (Logrono, Spain, July 7-10, 2015).
AB  - The 25th Congress of the Spanish Society for Microbiology (SEM) took place on 7
      10 July, 2015, at the University of La Rioja, in Logrono. This meeting brought
      together microbiologists from several prestigious universities and research
      centers throughout Spain, as well as experts from other countries including the
      United States, United Kingdom, Portugal, Germany, Mexico and Venezuela. The
      program included an opening lecture, one invited lecture and a closing lecture,
      twelve symposia on selected topics, ten sessions of oral presentations, four
      poster sessions, and three workshops. There were around 230 poster presentations
      and 55 oral communications. Relevant Spanish and foreign researchers participated
      at the symposia in order to get a straightforward vision of the new and more
      successful scientific results. Besides, joint symposia with the Portuguese
      Society for Microbiology as well as with the Spanish Society for Virology were
      held. One of the main goals of the meeting was to stimulate the participation of
      young microbiologists, given them an excellent opportunity to present their more
      recent results.

PMID- 27036739
TI  - Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin
      resistance phenotype: a therapeutic efficacy study.
AB  - BACKGROUND: Artemisinin resistance in Plasmodium falciparum extends across
      Southeast Asia where it is associated with worsening partner drug resistance and
      a decline in the efficacy of frontline artemisinin-based combination therapy.
      Dihydroartemisinin-piperaquine (DP) is an essential component of preventive and
      curative treatment in the region, but its therapeutic efficacy has fallen in
      Cambodia. METHODS: A prospective clinical and parasitological evaluation of DP
      was conducted at two sites in Upper Myanmar between August 2013 and December
      2014, enrolling 116 patients with acute uncomplicated falciparum malaria.
      Patients received DP orally for 3 days together with primaquine 0.25 mg/kg on
      admission. Parasite clearance half-lives based on 6 hourly blood smears, and day
      42 therapeutic responses were assessed as well as parasite K13 genotypes.
      RESULTS: Median parasite clearance half-life was prolonged, and clearance half
      life was greater than 5 h in 21% of patients. Delayed parasite clearance was
      significantly associated with mutations in the propeller region of the parasite
      k13 gene. The k13 F446I mutation was found in 25.4% of infections and was
      associated with a median clearance half-life of 4.7 h compared with 2.7 h for
      infections without k13 mutations (p < 0.001). There were no failures after 42
      days of follow-up, although 18% of patients had persistent parasitaemia on day 3.
      CONCLUSION: The dominant k13 mutation observed in Upper Myanmar, F446I, appears
      to be associated with an intermediate rate of parasite clearance compared to
      other common mutations described elsewhere in the Greater Mekong Subregion.
      Discerning this phenotype requires relatively detailed clearance measurements,
      highlighting the importance of methodology in assessing artemisinin resistance.

PMID- 27036741
TI  - The microbiome of urban waters.
AB  - More than 50% of the world's population lives in urban centers. As collection
      basins for landscape activity, urban waters are an interface between human
      activity and the natural environment. The microbiome of urban waters could
      provide insight into the impacts of pollution, the presence of human health
      risks, or the potential for long-term consequences for these ecosystems and the
      people who depend upon them. An integral part of the urban water cycle is sewer
      infrastructure. Thousands of miles of pipes line cities as part of wastewater and
      stormwater systems. As stormwater and sewage are released into natural waterways,
      traces of human and animal microbiomes reflect the sources and magnitude of fecal
      pollution and indicate the presence of pollutants, such as nutrients, pathogens,
      and chemicals. Non-fecal organisms are also released as part of these systems.
      Runoff from impervious surfaces delivers microbes from soils, plants and the
      built environment to stormwater systems. Further, urban sewer infrastructure
      contains its own unique microbial community seemingly adapted to this relatively
      new artificial habitat. High microbial densities are conveyed via pipes to
      waterways, and these organisms can be found as an urban microbial signature
      imprinted on the natural community of rivers and urban coastal waters. The
      potential consequences of mass releases of non-indigenous microorganisms into
      natural waters include creation of reservoirs for emerging human pathogens,
      altered nutrient flows into aquatic food webs, and increased genetic exchange
      between two distinct gene pools. This review highlights the recent
      characterization of the microbiome of urban sewer and stormwater infrastructure
      and its connection to and potential impact upon freshwater systems.

PMID- 27036742
TI  - Microbes, cables, and an electrical touch.
AB  - In nature, highly efficient and diverse consortia of microbes cycle carbon and
      other elements while generating energy for growth. Driving these reactions are
      organisms with the ability to extract electrons from the chemical substrates and
      transfer them to insoluble and soluble electron acceptors. One bacterial group in
      particular, Geobacter spp., can couple their respiratory metabolism to the
      reduction of insoluble minerals, such as iron and manganese oxides, and soluble
      toxic metals such as uranium. Key to these activities is the ability of the cells
      to transfer respiratory electrons extracellularly using an electroactive cell
      envelope containing abundant metalloproteins, including c-cytochromes, and
      conductive protein appendages or pili (known as nanowires). Thus, in addition to
      been ecological drivers of the cycling of carbon and metals in nature, these
      organisms show promise for the bioremediation of environments impacted with toxic
      metals. The electrical activity of Geobacter can also be mimicked in
      electrochemical reactors equipped with an electrode poised at a metabolically
      oxidizing potential, so that the electrode functions as an unlimited sink of
      electrons to drive the oxidation of electron donors and support cell growth.
      Electrochemical reactors are promising for the treatments of agricultural,
      industrial, and human wastes, and the electroactivity of these microbes can be
      used to develop materials and devices for bioenergy and bioremediation
      applications.

PMID- 27036743
TI  - Functional symbiosis and communication in microbial ecosystems. The case of wood
      eating termites and cockroaches.
AB  - Animal hosts typically have strong specificity for microbial symbionts and their
      functions. The symbiotic relationships have enhanced the limited metabolic
      networks of most eukaryotes by contributing several prokaryotic metabolic
      capabilities, such as methanogenesis, chemolithoautotrophy, nitrogen
      assimilation, etc. This review will examine the characteristics that determine
      bacterial "fidelity" to certain groups of animals (e.g., xylophagous insects,
      such as termites and cockroaches) over generations and throughout evolution. The
      hindgut bacteria of wood-feeding termites and cockroaches belong to several
      phyla, including Proteobacteria, especially Deltaproteobacteria, Bacteroidetes,
      Firmicutes, Actinomycetes, Spirochetes, Verrucomicrobia, and Actinobacteria, as
      detected by 16S rRNA. Termites effectively feed on many types of lignocelluloses
      assisted by their gut microbial symbionts. Although the community structures
      differ between the hosts (termites and cockroaches), with changes in the relative
      abundances of particular bacterial taxa, the composition of the bacterial
      community could reflect at least in part the host evolution in that the
      microbiota may derive from the microbiota of a common ancestor. Therefore,
      factors other than host phylogeny, such as diet could have had strong influence
      in shaping the bacterial community structure.

PMID- 27036744
TI  - Effect of propionic acid on Campylobacter jejuni attached to chicken skin during
      refrigerated storage.
AB  - The ability of propionic acid to reduce Campylobacter jejuni on chicken legs was
      evaluated. Chicken legs were inoculated with Campylobacter jejuni. After dipping
      legs in either water (control), 1% or 2% propionic acid solution (vol/vol), they
      were stored at 4oC for 8 days. Changes in C. jejuni, psychrotrophs and
      Pseudomonas counts were evaluated. Washing in 2% propionic acid significantly
      reduced C. jejuni counts compared to control legs, with a decrease of about 1.62
      log units after treatment. Treatment of chicken legs with 1 or 2% propionic acid
      significantly reduced numbers of psychrotrophs 1.01 and 1.08 log units and
      Pseudomonas counts 0.75 and 0.96 log units, respectively, compared to control
      legs. The reduction in psychrotrophs and Pseudomonas increased throughout
      storage. The highest reductions obtained for psychrotrophs and Pseudomonas counts
      in treated legs were reached at the end of storage, day 8, being 3.3 and 2.93 log
      units, respectively, compared to control legs. Propionic acid treatment was
      effective in reducing psychrotrophs and Pseudomonas counts on chicken legs
      throughout storage. It is concluded that propionic acid is effective for reducing
      C. jejuni populations in chicken.

PMID- 27036745
TI  - Contribution of vesicle-protected extracellular DNA to horizontal gene transfer
      in Thermus spp.
AB  - Highly efficient apparatus for natural competence and conjugation have been shown
      as the major contributors to horizontal gene transfer (HGT) in Thermus
      thermophilus. In practical terms, both mechanisms can be distinguished by the
      sensitivity of the former to the presence of DNAse, and the requirement for cell
      to cell contacts in the second. Here we demonstrate that culture supernatants of
      different strains of Thermus spp. produce DNAse-resistant extracellular DNA
      (eDNA) in a growth-rate dependent manner. This eDNA was double stranded, similar
      in size to isolated genomic DNA (around 20 kbp), and represented the whole genome
      of the producer strain. Protection against DNAse was the consequence of
      association of the eDNA to membrane vesicles which composition was shown to
      include a great diversity of cell envelope proteins with minor content of
      cytoplasmic proteins. Access of the recipient cell to the protected eDNA depended
      on the natural competence apparatus and elicited the DNA-DNA interference defence
      mediated by the Argonaute protein. We hypothesize on the lytic origin of the eDNA
      carrying vesicles and discuss the relevance of this alternative mechanism for HGT
      in natural thermal environments.

PMID- 27036746
TI  - Dormancy in Deinococcus sp. UDEC-P1 as a survival strategy to escape from
      deleterious effects of carbon starvation and temperature.
AB  - Dormancy is characterized by low metabolism and absence of protein synthesis and
      cellular division enabling bacterial cells to survive under stress. The aim was
      to determine if carbon starvation and low temperature are factors that modify the
      proportion of dormant/active cells in Deinococcus sp. UDEC-P1. By flow cytometry,
      RedoxSensor Green (RSG) was used to quantify metabolic activity and Propidium
      Iodide (PI) to evaluate membrane integrity in order to determine the percentage
      of dormant cells. Cell size and morphology were determined using scanning
      electronic microscopy. Under carbon starvation at 30 degrees C, Deinococcus sp.
      UDEC-P1 increased its proportion of dormant cells from 0.1% to 20%, decreased the
      count of culturable cells and average cell volume decreased 7.1 times. At 4
      degrees C, however, the proportion of dormant cells increased only to 6%, without
      a change in the count of culturable cells and an average cellular volume decrease
      of 4.1 times and 3% of the dormant cells were able to be awakened. Results
      indicate a greater proportion of dormant Deinococcus sp. UDEC-P1 cells at 30oC
      and it suggests that carbon starvation is more deleterious condition at 30oC than
      4oC. For this reason Deinococcus sp. UDEC-P1 cells are more likely to enter into
      dormancy at higher temperature as a strategy to survive.

PMID- 27036747
TI  - LERU roadmap towards Open Access.
AB  - Money which is not directly spent on research and education, even though it is
      largely taxpayers' money. As Harvard University already denounced in 2012, many
      large journal publishers have rendered the situation "fiscally unsustainable and
      academically restrictive", with some journals costing as much as $40,000 per year
      (and publishers drawing profits of 35% or more). If one of the wealthiest
      universities in the world can no longer afford it, who can? It is easy to picture
      the struggle of European universities with tighter budgets. In addition to
      subscription costs, academic research funding is also largely affected by
      "Article Processing Charges" (APC), which come at an additional cost of
      ?2000/article, on average, when making individual articles Gold Open Access. Some
      publishers are in this way even being paid twice for the same content ("double
      dipping"). In the era of Open Science, Open Access to publications is one of the
      cornerstones of the new research paradigm and business models must support this
      transition. It should be one of the principal objectives of Commissioner Carlos
      Moedas and the Dutch EU Presidency (January-June 2016) to ensure that this
      transition happens. Further developing the EU's leadership in research and
      innovation largely depends on it. With this statement "Moving Forwards on Open
      Access", LERU calls upon all universities, research institutes, research funders
      and researchers to sign this statement and give a clear signal towards the
      European Commission and the Dutch EU Presidency.

PMID- 27036748
TI  - Inbreeding depression does not increase after exposure to a stressful
      environment: a test using compensatory growth.
AB  - BACKGROUND: Inbreeding is often associated with a decrease in offspring fitness
      ('inbreeding depression'). Moreover, it is generally assumed that the negative
      effects of inbreeding are exacerbated in stressful environments. This G * E
      interaction has been explored in many taxa under different environmental
      conditions. These studies usually manipulate environmental conditions either in
      adulthood or throughout an individual's entire life. Far fewer studies have
      tested how stressful environments only experienced during development
      subsequently influence the effects of inbreeding on adult traits. RESULTS: We
      experimentally manipulated the diet (control versus low food) of inbred and
      outbred juvenile Eastern mosquitofish (Gambusia holbrooki) for three weeks (days
      7-28) to test whether experiencing a presumably stressful environment early in
      life influences their subsequent growth and adult phenotypes. The control diet
      was a standard laboratory food regime, while fish on the low food diet received
      less than 25 % of this amount of food. Unexpectedly, despite a large sample size
      (237 families, 908 offspring) and a quantified 23 % reduction in genome-wide
      heterozygosity in inbred offspring from matings between full-siblings (f = 0.25),
      neither inbreeding nor its interaction with early diet affected growth
      trajectories, juvenile survival or adult size. Individuals did not mitigate a
      poor start in life by showing 'compensatory growth' (i.e. faster growth once the
      low food treatment ended), but they showed 'catch-up growth' by delaying
      maturation. There was, however, no effect of inbreeding on the extent of catch-up
      growth. CONCLUSIONS: There were no detectable effects of inbreeding on growth or
      adult size, even on a low food diet that should elevate inbreeding depression.
      Thus, the long-term costs of inbreeding due to lower male reproductive success we
      have shown in another study appear to be unrelated to inbreeding depression for
      adult male size or the growth rates that are reported in the current study.

PMID- 27036749
TI  - Microcephaly and Zika virus.

PMID- 27036750
TI  - Erratum on "Association between physical activity, participation in Physical
      Education classes, and social isolation in adolescents".

PMID- 27036752
TI  - Active cancellation of residual amplitude modulation in a frequency-modulation
      based Fabry-Perot interferometer.
AB  - Residual amplitude modulation (RAM) is one of the most common noise sources known
      to degrade the sensitivity of frequency modulation spectroscopy. RAM can arise as
      a result of the temperature dependent birefringence of the modulator crystal,
      which causes the orientation of the crystal's optical axis to shift with respect
      to the polarization of the incident light with temperature. In the fiber-based
      optical interferometer used on the National Institute of Standards and Technology
      calculable capacitor, RAM degrades the measured laser frequency stability and
      correlates with the environmental temperature fluctuations. We have demonstrated
      a simple approach that cancels out excessive RAM due to polarization mismatch
      between the light and the optical axis of the crystal. The approach allows us to
      measure the frequency noise of a heterodyne beat between two lasers individually
      locked to different resonant modes of a cavity with an accuracy better than 0.5
      ppm, which meets the requirement to further determine the longitudinal mode
      number of the cavity length. Also, this approach has substantially mitigated the
      temperature dependency of the measurements of the cavity length and consequently
      the capacitance. 

PMID- 27036751
TI  - Invited Review Article: Pump-probe microscopy.
AB  - Multiphoton microscopy has rapidly gained popularity in biomedical imaging and
      materials science because of its ability to provide three-dimensional images at
      high spatial and temporal resolution even in optically scattering environments.
      Currently the majority of commercial and home-built devices are based on two
      photon fluorescence and harmonic generation contrast. These two contrast
      mechanisms are relatively easy to measure but can access only a limited range of
      endogenous targets. Recent developments in fast laser pulse generation, pulse
      shaping, and detection technology have made accessible a wide range of optical
      contrasts that utilize multiple pulses of different colors. Molecular excitation
      with multiple pulses offers a large number of adjustable parameters. For example,
      in two-pulse pump-probe microscopy, one can vary the wavelength of each
      excitation pulse, the detection wavelength, the timing between the excitation
      pulses, and the detection gating window after excitation. Such a large parameter
      space can provide much greater molecular specificity than existing single-color
      techniques and allow for structural and functional imaging without the need for
      exogenous dyes and labels, which might interfere with the system under study. In
      this review, we provide a tutorial overview, covering principles of pump-probe
      microscopy and experimental setup, challenges associated with signal detection
      and data processing, and an overview of applications. 

PMID- 27036753
TI  - A spatial light modulator that uses scattering in a cholesteric liquid crystal.
AB  - When a cholesteric liquid crystal (helical pitch: 5 MUm) was sandwiched between
      two glass plates with no alignment coating (gap: 20 MUm), a random-domain texture
      appeared and a strong light scattering took place. This translucent texture
      turned to a transparent homeotropic phase when an electric voltage of 20 V was
      applied to the liquid crystal layer. This phase transition was used for
      constructing a spatial light modulator that needed no polarizers. Indium-tin
      oxide electrodes (0.8 mm square) were arranged on a glass substrate to create a
      20 * 20 pixel array (20 mm square). The liquid crystal was injected into a gap
      (20 MUm thickness) between this substrate and another glass plate with a uniform
      electrode (ground). The transmittance of the pixels was originally below 10% and
      decreased to 0% by 7 V application because of increase in the scattering loss. As
      the voltage was raised, the transmittance increased gradually in the 7-17 V range
      and then rapidly in the 17-20 V range, attaining 40% at 27 V. Various
      transmittance distributions or gray-scale images were attainable by applying a
      suitable voltage (7-27 V) to each pixel. The transmission range of this spatial
      light modulator extended from ultraviolet (350 nm) to infrared wavelengths (>800
      nm). Owing to this wide transmission range as well as capability of the polarizer
      free operation, this spatial light modulator is useful to control a lamp spectrum
      in spectroscopic measurements. 

PMID- 27036754
TI  - An instrument combining an electrospray ionization source and a velocity-map
      imaging spectrometer for studying delayed electron emission of polyanions.
AB  - An instrument combining an electrospray ionization source and a velocity-map
      imaging (VMI) spectrometer has been developed in order to study the delayed
      electron emission of molecular anions and especially of polyanions. It operates
      at a high repetition rate (kHz) in order to increase the acquisition speed. The
      VMI spectrometer has been upgraded for nanosecond time resolution by gating the
      voltages applied on the position-sensitive detector. Kinetic energy release
      distribution of thermionic emission (without any contribution from direct
      detachment) can be recorded for well-defined delays after the nanosecond laser
      excitation. The capability of the instrument is demonstrated by recording
      photodetachment spectra of the benchmark C60(-) anion and C84(2-) dianion.

PMID- 27036755
TI  - High vacuum tip-enhanced Raman spectroscope based on a scanning tunneling
      microscope.
AB  - In this paper, we present the construction of a high-vacuum tip-enhanced Raman
      spectroscopy (HV-TERS) system that allows in situ sample preparation and
      measurement. A detailed description of the prototype instrument is presented with
      experimental validation of its use and novel ex situ experimental results using
      the HV-TERS system. The HV-TERS system includes three chambers held under a 10(
      7) Pa vacuum. The three chambers are an analysis chamber, a sample preparation
      chamber, and a fast loading chamber. The analysis chamber is the core chamber and
      contains a scanning tunneling microscope (STM) and a Raman detector coupled with
      a 50 * 0.5 numerical aperture objective. The sample preparation chamber is used
      to produce single-crystalline metal and sub-monolayer molecular films by
      molecular beam epitaxy. The fast loading chamber allows ex situ preparation of
      samples for HV-TERS analysis. Atomic resolution can be achieved by the STM on
      highly ordered pyrolytic graphite. We demonstrate the measurement of localized
      temperature using the Stokes and anti-Stokes TERS signals from a monolayer of 1,2
      benzenedithiol on a gold film using a gold tip. Additionally, plasmonic catalysis
      can be monitored label-free at the nanoscale using our device. Moreover, the HV
      TERS experiments show simultaneously activated infrared and Raman vibrational
      modes, Fermi resonance, and some other non-linear effects that are not observed
      in atmospheric TERS experiments. The high spatial and spectral resolution and
      pure environment of high vacuum are beneficial for basic surface studies. 

PMID- 27036756
TI  - A passive terahertz video camera based on lumped element kinetic inductance
      detectors.
AB  - We have developed a passive 350 GHz (850 MUm) video-camera to demonstrate lumped
      element kinetic inductance detectors (LEKIDs)--designed originally for far
      infrared astronomy--as an option for general purpose terrestrial terahertz
      imaging applications. The camera currently operates at a quasi-video frame rate
      of 2 Hz with a noise equivalent temperature difference per frame of ~0.1 K, which
      is close to the background limit. The 152 element superconducting LEKID array is
      fabricated from a simple 40 nm aluminum film on a silicon dielectric substrate
      and is read out through a single microwave feedline with a cryogenic low noise
      amplifier and room temperature frequency domain multiplexing electronics.

PMID- 27036757
TI  - Ghost fringe removal techniques using Lissajous data presentation.
AB  - A VISAR (Velocity Interferometer System for Any Reflector) is a Doppler velocity
      interferometer which is an important optical diagnostic in shockwave experiments
      at the national laboratories, used to measure equation of state (EOS) of
      materials under extreme conditions. Unwanted reflection of laser light from
      target windows can produce an additional component to the VISAR fringe record
      that can distort and obscure the true velocity signal. Accurately removing this
      so-called ghost artifact component is essential for achieving high accuracy EOS
      measurements, especially when the true light signal is only weakly reflected from
      the shock front. Independent of the choice of algorithm for processing the raw
      data into a complex fringe signal, we have found it beneficial to plot this
      signal as a Lissajous and seek the proper center of this path, even under time
      varying intensity which can shift the perceived center. The ghost contribution is
      then solved by a simple translation in the complex plane that recenters the
      Lissajous path. For continuous velocity histories, we find that plotting the
      fringe magnitude vs nonfringing intensity and optimizing linearity is an
      invaluable tool for determining accurate ghost offsets. For discontinuous
      velocity histories, we have developed graphically inspired methods which relate
      the results of two VISARs having different velocity per fringe proportionalities
      or assumptions of constant fringe magnitude to find the ghost offset. The
      technique can also remove window reflection artifacts in generic interferometers,
      such as in the metrology of surfaces. 

PMID- 27036758
TI  - Development of compartment for studies on the growth of protein crystals in
      space.
AB  - To clarify the growth mechanism of a protein crystal, it is essential to measure
      its growth rate with respect to the supersaturation. We developed a compartment
      (growth cell) for measuring the growth rate (<0.1 nm s(-1)) of the face of a
      protein crystal at a controlled supersaturation by interferometry over a period
      of half a year in space. The growth cell mainly consists of quartz glass, in
      which the growth solution and a seed crystal are enclosed by capillaries, the
      screw sample holder, and a helical insert. To avoid the destruction of the cell
      and the evaporation of the water from the solution inside the cell, we selected
      the materials for these components with care. The equipment was successfully used
      to examine the growth of a lysozyme crystal at a controlled supersaturation in
      space, where convection is negligible because of the microgravity environment,
      thereby advancing our understanding of the mechanism of protein crystal growth
      from solution. The technique used to develop the growth cell is useful not only
      for space experiments but also for kinetic studies of materials with very slow
      growth and dissolution rates (<10(-3) nm s(-1)). 

PMID- 27036759
TI  - Optimizing array spectroradiometer readings using adaptative bracketing.
AB  - Single monochromator array spectroradiometers are convenient instruments for
      measuring spectral quantities in the UV-Vis-NIR range. They monitor the sensor
      array signal based on the same integration time for all wavelengths. However, the
      signal-to-noise ratio may be too low to provide useful readings at weaker signal
      wavelengths. The so-called "bracketing" technique overcomes this drawback by
      performing successive retrievals using different integration times, thereby
      ensuring that sufficiently high signal-to-noise ratio signals are recorded and
      non-relevant and low ratio signals are ignored. This paper proposes the use of an
      automated bracketing method based on the currently used array spectroradiometer
      noise models and analysis of retrieved spectra. Integration time at each array
      pixel fits spectral signal distribution with respect to a user-defined accuracy
      criterion and relevance constraints for the spectroradiometer used. 

PMID- 27036760
TI  - Active phase locking of thirty fiber channels using multilevel phase dithering
      method.
AB  - An active phase locking of a large-scale fiber array with thirty channels has
      been demonstrated experimentally. In the experiment, the first group of thirty
      phase controllers is used to compensate the phase noises between the elements and
      the second group of thirty phase modulators is used to impose additional phase
      disturbances to mimic the phase noises in the high power fiber amplifiers. A
      multi-level phase dithering algorithm using dual-level rectangular-wave phase
      modulation and time division multiplexing can achieve the same phase control as
      single/multi-frequency dithering technique, but without coherent demodulation
      circuit. The phase locking efficiency of 30 fiber channels is achieved about
      98.68%, 97.82%, and 96.50% with no additional phase distortion, modulated phase
      distortion I (+/-1 rad), and phase distortion II (+/-2 rad), corresponding to the
      phase error of lambda/54, lambda/43, and lambda/34 rms. The contrast of the
      coherent combined beam profile is about 89%. Experimental results reveal that the
      multi-level phase dithering technique has great potential in scaling to a large
      number of laser beams. 

PMID- 27036762
TI  - A cryogenic optical feedthrough using polarization maintaining fibers.
AB  - Polarization maintaining optical fibers can be used to transmit linearly
      polarized light over long distances but their use in cryogenic environments has
      been limited by their sensitivity to temperature changes and associated
      mechanical stress. We investigate experimentally how thermal stresses affect the
      polarization maintaining fibers and model the observations with Jones matrices.
      We describe the design, construction, and testing of a feedthrough and fiber
      termination assembly that uses polarization maintaining fiber to transmit light
      from a 633 nm HeNe laser at room temperature to a homodyne polarization-based
      interferometer in a cryogenic vacuum. We report on the efficiency of the
      polarization maintaining properties of the feedthrough assembly. We also report
      that, at cryogenic temperatures, the interferometer can achieve a sensitivity of
      8 * 10(-10) rad/?Hz at 0.05 Hz using this feedthrough.

PMID- 27036761
TI  - Femtosecond X-ray magnetic circular dichroism absorption spectroscopy at an X-ray
      free electron laser.
AB  - X-ray magnetic circular dichroism spectroscopy using an X-ray free electron laser
      is demonstrated with spectra over the Fe L(3,2)-edges. The high brightness of the
      X-ray free electron laser combined with high accuracy detection of incident and
      transmitted X-rays enables ultrafast X-ray magnetic circular dichroism studies of
      unprecedented sensitivity. This new capability is applied to a study of all
      optical magnetic switching dynamics of Fe and Gd magnetic sublattices in a GdFeCo
      thin film above its magnetization compensation temperature.

PMID- 27036763
TI  - Pixel multiplexing technique for real-time three-dimensional-imaging laser
      detection and ranging system using four linear-mode avalanche photodiodes.
AB  - The avalanche-photodiode-array (APD-array) laser detection and ranging (LADAR)
      system has been continually developed owing to its superiority of nonscanning,
      large field of view, high sensitivity, and high precision. However, how to
      achieve higher-efficient detection and better integration of the LADAR system for
      real-time three-dimensional (3D) imaging continues to be a problem. In this
      study, a novel LADAR system using four linear mode APDs (LmAPDs) is developed for
      high-efficient detection by adopting a modulation and multiplexing technique.
      Furthermore, an automatic control system for the array LADAR system is proposed
      and designed by applying the virtual instrumentation technique. The control
      system aims to achieve four functions: synchronization of laser emission and
      rotating platform, multi-channel synchronous data acquisition, real-time Ethernet
      upper monitoring, and real-time signal processing and 3D visualization. The
      structure and principle of the complete system are described in the paper. The
      experimental results demonstrate that the LADAR system is capable of achieving
      real-time 3D imaging on an omnidirectional rotating platform under the control of
      the virtual instrumentation system. The automatic imaging LADAR system utilized
      only 4 LmAPDs to achieve 256-pixel-per-frame detection with by employing 64-bit
      demodulator. Moreover, the lateral resolution is ~15 cm and range accuracy is ~4
      cm root-mean-square error at a distance of ~40 m. 

PMID- 27036764
TI  - Transparent electrodes for high E-field production using a buried indium tin
      oxide layer.
AB  - We present a design and characterization of optically transparent electrodes
      suitable for atomic and molecular physics experiments where high optical access
      is required. The electrodes can be operated in air at standard atmospheric
      pressure and do not suffer electrical breakdown even for electric fields far
      exceeding the dielectric breakdown of air. This is achieved by putting an indium
      tin oxide coated dielectric substrate inside a stack of dielectric substrates,
      which prevents ion avalanche resulting from Townsend discharge. With this design,
      we observe no arcing for fields of up to 120 kV/cm. Using these plates, we
      directly verify the production of electric fields up to 18 kV/cm inside a quartz
      vacuum cell by a spectroscopic measurement of the dc Stark shift of the
      5(2)S(1/2) -> 5(2)P(3/2) transition for a cloud of laser cooled rubidium atoms.
      We also report on the shielding of the electric field and on the residual
      electric fields that persist within the vacuum cell once the electrodes are
      discharged. In addition, we discuss observed atom loss that results from the
      motion of free charges within the vacuum. The observed asymmetry of these
      phenomena on the bias of the electrodes suggests that field emission of electrons
      within the vacuum is primarily responsible for these effects and may indicate a
      way of mitigating them.

PMID- 27036765
TI  - Development of a compact vertical-cavity surface-emitting laser end-pumped
      actively Q-switched laser for laser-induced breakdown spectroscopy.
AB  - This paper reports the development of a compact and portable actively Q-switched
      Nd:YAG laser and its applications in laser-induced breakdown spectroscopy (LIBS).
      The laser was end-pumped by a vertical-cavity surface-emitting laser (VCSEL). The
      cavity lases at a wavelength of 1064 nm and produced pulses of 16 ns with a
      maximum pulse energy of 12.9 mJ. The laser exhibits a reliable performance in
      terms of pulse-to-pulse stability and timing jitter. The LIBS experiments were
      carried out using this laser on NIST standard alloy samples. Shot-to-shot LIBS
      signal stability, crater profile, time evolution of emission spectra, plasma
      electron density and temperature, and limits of detection were studied and
      reported in this paper. The test results demonstrate that the VCSEL-pumped solid
      state laser is an effective and compact laser tool for laser remote sensing
      applications. 

PMID- 27036766
TI  - Emittance and lifetime measurement with damping wigglers.
AB  - National Synchrotron Light Source II (NSLS-II) is a new third-generation storage
      ring light source at Brookhaven National Laboratory. The storage ring design
      calls for small horizontal emittance (<1 nm-rad) and diffraction-limited vertical
      emittance at 12 keV (8 pm-rad). Achieving low value of the beam size will enable
      novel user experiments with nm-range spatial and meV-energy resolution. The high
      brightness NSLS-II lattice has been realized by implementing 30-cell double bend
      achromatic cells producing the horizontal emittance of 2 nm rad and then halving
      it further by using several Damping Wigglers (DWs). This paper is focused on
      characterization of the DW effects in the storage ring performance, namely, on
      reduction of the beam emittance, and corresponding changes in the energy spread
      and beam lifetime. The relevant beam parameters have been measured by the X-ray
      pinhole camera, beam position monitors, beam filling pattern monitor, and current
      transformers. In this paper, we compare the measured results of the beam
      performance with analytic estimates for the complement of the 3 DWs installed at
      the NSLS-II. 

PMID- 27036767
TI  - A high-resolution time-of-flight energy analyzer for femtosecond electron pulses
      at 30 keV.
AB  - We report a time-of-flight spectrometer for electron pulses at up to 30 keV,
      which is a suitable energy for atomic-resolution femtosecond investigations via
      time-resolved electron diffraction, microscopy, and energy loss spectroscopy. For
      realistic femtosecond beams without apertures, the instrument's energy resolution
      is ~0.5 eV (full width at half maximum) or 2 * 10(-5) at a throughput of 50%-90%.
      We demonstrate the analyzer's versatility by three first applications, namely,
      femtosecond electron pulse metrology via optical streaking, in situ drift
      correction in laser-microwave synchronization for electron pulse compression, and
      time-resolved electron energy loss spectroscopy of aluminum, showing the
      instrument's capability of tracking plasmonic loss peak positions with few-meV
      accuracy. 

PMID- 27036768
TI  - Electrical-thermal-structural finite element simulation and experimental study of
      a plasma ion source for the production of radioactive ion beams.
AB  - The production target and the ion source constitute the core of the selective
      production of exotic species (SPES) facility. In this complex experimental
      apparatus for the production of radioactive ion beams, a 40 MeV, 200 MUA proton
      beam directly impinges a uranium carbide target, generating approximately 10(13)
      fissions per second. The transfer line enables the unstable isotopes generated by
      the (238)U fissions in the target to reach the ion source, where they can be
      ionized and finally accelerated to the subsequent areas of the facility. In this
      work, the plasma ion source currently adopted for the SPES facility is analyzed
      in detail by means of electrical, thermal, and structural numerical models. Next,
      theoretical results are compared with the electric potential difference,
      temperature, and displacement measurements. Experimental tests with stable ion
      beams are also presented and discussed. 

PMID- 27036769
TI  - Development of a Ne gas target for (22)Na production by proton irradiation.
AB  - The article presents the design and development of a neon gas target for the
      production of (22)Na using a proton beam from the room temperature cyclotron in
      Variable Energy Cyclotron Centre, Kolkata. The target design is made to handle a
      beam power of 85 W (17 MeV, 5 MUA). The design is based on simulation using the
      computer code FLUKA for the beam dump and CFD-CFX for target cooling. The target
      has been successfully used for the production of (22)Na in a 6 day long 17 MeV, 5
      MUA proton irradiation run. 

PMID- 27036770
TI  - Hybrid de-noising approach for fiber optic gyroscopes combining improved
      empirical mode decomposition and forward linear prediction algorithms.
AB  - A noise reduction algorithm based on an improved empirical mode decomposition
      (EMD) and forward linear prediction (FLP) is proposed for the fiber optic
      gyroscope (FOG). Referred to as the EMD-FLP algorithm, it was developed to
      decompose the FOG outputs into a number of intrinsic mode functions (IMFs) after
      which mode manipulations are performed to select noise-only IMFs, mixed IMFs, and
      residual IMFs. The FLP algorithm is then employed to process the mixed IMFs, from
      which the refined IMFs components are reconstructed to produce the final de
      noising results. This hybrid approach is applied to, and verified using, both
      simulated signals and experimental FOG outputs. The results from the applications
      show that the method eliminates noise more effectively than the conventional EMD
      or FLP methods and decreases the standard deviations of the FOG outputs after de
      noising from 0.17 to 0.026 under sweep frequency vibration and from 0.22 to 0.024
      under fixed frequency vibration. 

PMID- 27036771
TI  - Design of a portable optical emission tomography system for microwave induced
      compact plasma for visible to near-infrared emission lines.
AB  - A new non-invasive diagnostic system is developed for Microwave Induced Plasma
      (MIP) to reconstruct tomographic images of a 2D emission profile. A compact MIP
      system has wide application in industry as well as research application such as
      thrusters for space propulsion, high current ion beams, and creation of negative
      ions for heating of fusion plasma. Emission profile depends on two crucial
      parameters, namely, the electron temperature and density (over the entire spatial
      extent) of the plasma system. Emission tomography provides basic understanding of
      plasmas and it is very useful to monitor internal structure of plasma phenomena
      without disturbing its actual processes. This paper presents development of a
      compact, modular, and versatile Optical Emission Tomography (OET) tool for a
      cylindrical, magnetically confined MIP system. It has eight slit-hole cameras and
      each consisting of a complementary metal-oxide-semiconductor linear image sensor
      for light detection. The optical noise is reduced by using aspheric lens and
      interference band-pass filters in each camera. The entire cylindrical plasma can
      be scanned with automated sliding ring mechanism arranged in fan-beam data
      collection geometry. The design of the camera includes a unique possibility to
      incorporate different filters to get the particular wavelength light from the
      plasma. This OET system includes selected band-pass filters for particular argon
      emission 750 nm, 772 nm, and 811 nm lines and hydrogen emission H(alpha) (656 nm)
      and H(beta) (486 nm) lines. Convolution back projection algorithm is used to
      obtain the tomographic images of plasma emission line. The paper mainly focuses
      on (a) design of OET system in detail and (b) study of emission profile for 750
      nm argon emission lines to validate the system design.

PMID- 27036772
TI  - In situ measurement of the two-dimensional temperature field of a dual-jet direct
      current arc plasma.
AB  - In this paper, a real time method for an in situ measurement of the two
      dimensional (2-D) temperature filed of thermal plasmas is developed with the
      combination of the visible image processing technique and the spectroscopic line
      ratio method at two specified wavelengths. After the calibration of the gray
      scale values of the recorded images with the CCD cameras by the emission
      intensity received using a spectrometer, the 2-D temperature field of the plasma
      arc-jet can be obtained conveniently based on the derived gray scale values of
      the CCD images at two specified wavelengths and the formula similar to that of
      spectroscopic line-ratio method. The experimental results show that the obtained
      temperature fields of the plasma arc-jet at different times are qualitatively
      reasonable and consistent with the modeling result. This newly developed method
      can be employed to measure the transient temperature fields of the plasmas with
      fluctuations during discharges effectively. 

PMID- 27036773
TI  - A multiple gap plasma cathode electron gun and its electron beam analysis in self
      and trigger breakdown modes.
AB  - In the present paper, a pseudospark discharge based multiple gap plasma cathode
      electron gun is reported which has been operated separately in self and trigger
      breakdown modes using two different gases, namely, argon and hydrogen. The beam
      current and beam energy have been analyzed using a concentric ring diagnostic
      arrangement. Two distinct electron beams are clearly seen with hollow cathode and
      conductive phases. The hollow cathode phase has been observed for ~50 ns where
      the obtained electron beam is having low beam current density and high energy.
      While in conductive phase it is high current density and low energy electron
      beam. It is inferred that in the hollow cathode phase the beam energy is more for
      the self breakdown case whereas the current density is more for the trigger
      breakdown case. The tailor made operation of the hollow cathode phase electron
      beam can play an important role in microwave generation. Up to 30% variation in
      the electron beam energy has been achieved keeping the same gas and by varying
      the breakdown mode operations. Also, up to 32% variation in the beam current
      density has been achieved for the trigger breakdown mode at optimized trigger
      position by varying the gas type. 

PMID- 27036774
TI  - A 10(9) neutrons/pulse transportable pulsed D-D neutron source based on flexible
      head plasma focus unit.
AB  - A 17 kJ transportable plasma focus (PF) device with flexible transmission lines
      is developed and is characterized. Six custom made capacitors are used for the
      capacitor bank (CB). The common high voltage plate of the CB is fixed to a
      centrally triggered spark gap switch. The output of the switch is coupled to the
      PF head through forty-eight 5 m long RG213 cables. The CB has a quarter time
      period of 4 MUs and an estimated current of 506 kA is delivered to the PF device
      at 17 kJ (60 MUF, 24 kV) energy. The average neutron yield measured using silver
      activation detector in the radial direction is (7.1 +/- 1.4) * 10(8)
      neutrons/shot over 4pi sr at 5 mbar optimum D2 pressure. The average neutron
      yield is more in the axial direction with an anisotropy factor of 1.33 +/- 0.18.
      The average neutron energies estimated in the axial as well as in the radial
      directions are (2.90 +/- 0.20) MeV and (2.58 +/- 0.20) MeV, respectively. The
      flexibility of the PF head makes it useful for many applications where the source
      orientation and the location are important factors. The influence of
      electromagnetic interferences from the CB as well as from the spark gap on
      applications area can be avoided by putting a suitable barrier between the bank
      and the PF head. 

PMID- 27036775
TI  - Plasma crystal dynamics measured with a three-dimensional plenoptic camera.
AB  - Three-dimensional (3D) imaging of a single-layer plasma crystal was performed
      using a commercial plenoptic camera. To enhance the out-of-plane oscillations of
      particles in the crystal, the mode-coupling instability (MCI) was triggered in it
      by lowering the discharge power below a threshold. 3D coordinates of all
      particles in the crystal were extracted from the recorded videos. All three
      fundamental wave modes of the plasma crystal were calculated from these data. In
      the out-of-plane spectrum, only the MCI-induced hot spots (corresponding to the
      unstable hybrid mode) were resolved. The results are in agreement with theory and
      show that plenoptic cameras can be used to measure the 3D dynamics of plasma
      crystals. 

PMID- 27036776
TI  - Electrical probe characteristic recovery by measuring only one time-dependent
      parameter.
AB  - Two straightforward methods for recovering the current-voltage characteristic of
      an electrical probe are proposed. Basically, they consist of replacing the usual
      power supply from the probe circuit with a capacitor which can be charged or
      discharged by the probe current drained from the plasma. The experiment requires
      the registration of only one time-dependent electrical parameter, either the
      probe current or the probe voltage. The corresponding time-dependence of the
      second parameter, the probe voltage, or the probe current, respectively, can be
      calculated using an integral or a differential relation and the current-voltage
      characteristic of the probe can be obtained. 

PMID- 27036777
TI  - Apparatus for generating quasi-free-space microwave-driven plasmas.
AB  - An apparatus for generating quasi-free-space microwave-driven plasmas has been
      designed, constructed, and tested. The plasma is driven by a multi-kW, ~5 GHz
      microwave beam focused at the center of a vacuum chamber using a Koch-type metal
      plate lens. Sustained plasma discharges have been generated in argon at pressures
      ranging from 150 to 200 mTorr, at beam power levels ranging from 5 to 10 kW, and
      at gas flow rates of approximately 200 SCCM. 

PMID- 27036778
TI  - A confocal optical microscope for detection of single impurities in a bulk
      crystal at cryogenic temperatures.
AB  - A compact sample-scanning confocal optical microscope for detection of single
      impurities below the surface of a bulk crystal at cryogenic temperatures is
      described. The sample, lens, and scanners are mounted inside a helium bath
      cryostat and have a footprint of only 19 * 19 mm. Wide field imaging and confocal
      imaging using a Blu-ray lens immersed in liquid helium are demonstrated with
      excitation at 370 nm. A spatial resolution of 300 nm and a detection efficiency
      of 1.6% were achieved. 

PMID- 27036779
TI  - Lanthanide-based laser-induced phosphorescence for spray diagnostics.
AB  - Laser-induced phosphorescence (LIP) is a relatively recent and versatile
      development for studying flow dynamics. This work investigates certain lanthanide
      based molecular complexes for their use in LIP for high-speed sprays. Lanthanide
      complexes in solutions have been shown to possess long phosphorescence lifetimes
      (~1-2 ms) and to emit light in the visible wavelength range. In particular,
      europium and terbium complexes are investigated using
      fluorescence/phosphorescence spectrometry, showing that europium
      thenoyltrifluoracetone-trioctylphosphineoxide (Eu-TTA-TOPO) can be easily and
      efficiently excited using a standard frequency-tripled Nd:YAG laser. The emitted
      spectrum, with maximum intensity at a wavelength of 614 nm, is shown not to vary
      strongly with temperature (293-383 K). The decay constant of the phosphorescence,
      while independent of ambient pressure, decreases by approximately 12 MUs/K
      between 323 and 373 K, with the base level of the decay constant dependent on the
      used solvent. The complex does not luminesce in the gas or solid state, meaning
      only the liquid phase is visualized, even in an evaporating spray. By using an
      internally excited spray containing the phosphorescent complex, the effect of
      vaporization is shown through the decrease in measured intensity over the length
      of the spray, together with droplet size measurements using interferometric
      particle imaging. This study shows that LIP, using the Eu-TTA-TOPO complex, can
      be used with different solvents, including diesel surrogates. Furthermore, it can
      be easily handled and used in sprays to investigate spray breakup and
      evaporation. 

PMID- 27036780
TI  - Electron-bombarded ?110?-oriented tungsten tips for stable tunneling electron
      emission.
AB  - A clean tungsten (W) tip apex with a robust atomic plane is required for
      producing a stable tunneling electron emission under strong electric fields.
      Because a tip apex fabricated from a wire by aqueous chemical etching is covered
      by impurity layers, heating treatment in ultra-high vacuum is experimentally
      known to be necessary. However, strong heating frequently melts the tip apex and
      causes unstable electron emissions. We investigated quantitatively the tip apex
      and found a useful method to prepare a tip with stable tunneling electron
      emissions by controlling electron-bombardment heating power. Careful
      characterizations of the tip structures were performed with combinations of using
      field emission I-V curves, scanning electron microscopy, X-ray diffraction
      (transmitted Debye-Scherrer and Laue) with micro-parabola capillary, field ion
      microscopy, and field emission microscopy. Tips were chemically etched from (1)
      polycrystalline W wires (grain size ~1000 nm) and (2) long-time heated W wires
      (grain size larger than 1 mm). Heating by 10-40 W (10 s) was found to be good
      enough to remove oxide layers and produced stable electron emission; however,
      around 60 W (10 s) heating was threshold power to increase the tip radius,
      typically +10 +/- 5 nm (onset of melting). Further, the grain size of ~1000 nm
      was necessary to obtain a conical shape tip apex. 

PMID- 27036781
TI  - Daniell method for power spectral density estimation in atomic force microscopy.
AB  - An alternative method for power spectral density (PSD) estimation--the Daniell
      method--is revisited and compared to the most prevalent method used in the field
      of atomic force microscopy for quantifying cantilever thermal motion--the
      Bartlett method. Both methods are shown to underestimate the Q factor of a simple
      harmonic oscillator (SHO) by a predictable, and therefore correctable, amount in
      the absence of spurious deterministic noise sources. However, the Bartlett method
      is much more prone to spectral leakage which can obscure the thermal spectrum in
      the presence of deterministic noise. By the significant reduction in spectral
      leakage, the Daniell method leads to a more accurate representation of the true
      PSD and enables clear identification and rejection of deterministic noise peaks.
      This benefit is especially valuable for the development of automated PSD fitting
      algorithms for robust and accurate estimation of SHO parameters from a thermal
      spectrum.

PMID- 27036782
TI  - Optical cell tracking analysis using a straight-forward approach to minimize
      processing time for high frame rate data.
AB  - Tracking of rolling cells via in vitro experiment is now commonly performed using
      customized computer programs. In most cases, two critical challenges continue to
      limit analysis of cell rolling data: long computation times due to the complexity
      of tracking algorithms and difficulty in accurately correlating a given cell with
      itself from one frame to the next, which is typically due to errors caused by
      cells that either come close in proximity to each other or come in contact with
      each other. In this paper, we have developed a sophisticated, yet simple and
      highly effective, rolling cell tracking system to address these two critical
      problems. This optical cell tracking analysis (OCTA) system first employs ImageJ
      for cell identification in each frame of a cell rolling video. A custom MATLAB
      code was written to use the geometric and positional information of all cells as
      the primary parameters for matching each individual cell with itself between
      consecutive frames and to avoid errors when tracking cells that come within close
      proximity to one another. Once the cells are matched, rolling velocity can be
      obtained for further analysis. The use of ImageJ for cell identification
      eliminates the need for high level MATLAB image processing knowledge. As a
      result, only fundamental MATLAB syntax is necessary for cell matching. OCTA has
      been implemented in the tracking of endothelial colony forming cell (ECFC)
      rolling under shear. The processing time needed to obtain tracked cell data from
      a 2 min ECFC rolling video recorded at 70 frames per second with a total of over
      8000 frames is less than 6 min using a computer with an Intel(r) CoreTM i7 CPU
      2.80 GHz (8 CPUs). This cell tracking system benefits cell rolling analysis by
      substantially reducing the time required for post-acquisition data processing of
      high frame rate video recordings and preventing tracking errors when individual
      cells come in close proximity to one another. 

PMID- 27036783
TI  - First set of gated x-ray imaging diagnostics for the Laser Megajoule facility.
AB  - The Laser Megajoule (LMJ) facility located at CEA/CESTA started to operate in the
      early 2014 with two quadruplets (20 kJ at 351 nm) focused on target for the first
      experimental campaign. We present here the first set of gated x-ray imaging (GXI)
      diagnostics implemented on LMJ since mid-2014. This set consists of two imaging
      diagnostics with spatial, temporal, and broadband spectral resolution. These
      diagnostics will give basic measurements, during the entire life of the facility,
      such as position, structure, and balance of beams, but they will also be used to
      characterize gas filled target implosion symmetry and timing, to study x-ray
      radiography and hydrodynamic instabilities. The design requires a vulnerability
      approach, because components will operate in a harsh environment induced by
      neutron fluxes, gamma rays, debris, and shrapnel. Grazing incidence x-ray
      microscopes are fielded as far as possible away from the target to minimize
      potential damage and signal noise due to these sources. These imaging diagnostics
      incorporate microscopes with large source-to-optic distance and large size gated
      microchannel plate detectors. Microscopes include optics with grazing incidence
      mirrors, pinholes, and refractive lenses. Spatial, temporal, and spectral
      performances have been measured on x-ray tubes and UV lasers at CEA-DIF and at
      Physikalisch-Technische Bundesanstalt BESSY II synchrotron prior to be set on
      LMJ. GXI-1 and GXI-2 designs, metrology, and first experiments on LMJ are
      presented here. 

PMID- 27036784
TI  - Spatial-scanning hyperspectral imaging probe for bio-imaging applications.
AB  - The three common methods to perform hyperspectral imaging are the spatial
      scanning, spectral-scanning, and snapshot methods. However, only the spectral
      scanning and snapshot methods have been configured to a hyperspectral imaging
      probe as of today. This paper presents a spatial-scanning (pushbroom)
      hyperspectral imaging probe, which is realized by integrating a pushbroom
      hyperspectral imager with an imaging probe. The proposed hyperspectral imaging
      probe can also function as an endoscopic probe by integrating a custom fabricated
      image fiber bundle unit. The imaging probe is configured by incorporating a
      gradient-index lens at the end face of an image fiber bundle that consists of
      about 50,000 individual fiberlets. The necessary simulations, methodology, and
      detailed instrumentation aspects that are carried out are explained followed by
      assessing the developed probe's performance. Resolution test targets such as
      United States Air Force chart as well as bio-samples such as chicken breast
      tissue with blood clot are used as test samples for resolution analysis and for
      performance validation. This system is built on a pushbroom hyperspectral imaging
      system with a video camera and has the advantage of acquiring information from a
      large number of spectral bands with selectable region of interest. The advantages
      of this spatial-scanning hyperspectral imaging probe can be extended to test
      samples or tissues residing in regions that are difficult to access with
      potential diagnostic bio-imaging applications.

PMID- 27036785
TI  - Compact spherical neutron polarimeter using high-T(c) YBCO films.
AB  - We describe a simple, compact device for spherical neutron polarimetry
      measurements at small neutron scattering angles. The device consists of a sample
      chamber with very low (<0.01 G) magnetic field flanked by regions within which
      the neutron polarization can be manipulated in a controlled manner. This allows
      any selected initial and final polarization direction of the neutrons to be
      obtained. We have constructed a prototype device using high-T(c) superconducting
      films and mu-metal to isolate regions with different magnetic fields and tested
      device performance in transmission geometry. Finite-element methods were used to
      simulate the device's field profile and these have been verified by experiment
      using a small solenoid as a test sample. Measurements are reported using both
      monochromatic and polychromatic neutron sources. The results show that the device
      is capable of extracting sample information and distinguishing small angular
      variations of the sample magnetic field. As a more realistic test, we present
      results on the characterization of a 10 MUm thick Permalloy film in zero magnetic
      field, as well as its response to an external magnetic field.

PMID- 27036787
TI  - A new tribological experimental setup to study confined and sheared monolayers.
AB  - We have developed an original experimental setup, coupling tribology, and
      velocimetry experiments together with a direct visualization of the contact. The
      significant interest of the setup is to measure simultaneously the apparent
      friction coefficient and the velocity of confined layers down to molecular scale.
      The major challenge of this experimental coupling is to catch information on a
      nanometer-thick sheared zone confined between a rigid spherical indenter of
      millimetric radius sliding on a flat surface at constant speed. In order to
      demonstrate the accuracy of this setup to investigate nanometer-scale sliding
      layers, we studied a model lipid monolayer deposited on glass slides. It shows
      that our experimental setup will, therefore, help to highlight the hydrodynamic
      of such sheared confined layers in lubrication, biolubrication, or friction on
      solid polymer. 

PMID- 27036786
TI  - Experimental investigation of defect-assisted and intrinsic water vapor
      permeation through ultrabarrier films.
AB  - In the development of ultrabarrier films for packaging electronics, the effective
      water vapor transmission rate is a combination of permeation through pinhole
      defects and the intrinsic permeation through the actual barrier film. While it is
      possible to measure the effective permeation rate through barriers, it is
      important to develop a better understanding of the contribution from defects to
      the overall effective barrier performance. Here, we demonstrate a method to
      investigate independently defect-assisted permeation and intrinsic permeation
      rates by observing the degradation of a calcium layer encapsulated with a hybrid
      barrier film, that is, prepared using atomic layer deposition (ALD) and plasma
      enhanced deposition (PECVD). The results are rationalized using an analytical
      diffusion model to calculate the permeation rate as a function of spatial
      position within the barrier. It was observed that a barrier film consisting of a
      PECVD SiN(x) layer combined with an ALD Al2O3/HfO(x) nanolaminate resulted in a
      defect-assisted water vapor transmission rate (WVTR) of 4.84 * 10(-5) g/m(2) day
      and intrinsic WVTR of 1.41 * 10(-4) g/m(2) day at 50  degrees C/85% RH. Due to
      the low defect density of the tested barrier film, the defect-assisted WVTR was
      found to be three times lower than the intrinsic WVTR, and an effective (or
      total) WVTR value was 1.89 * 10(-4) g/m(2) day. Thus, improvements of the barrier
      performance should focus on reducing the number of defects while also improving
      the intrinsic barrier performance of the hybrid layer.

PMID- 27036788
TI  - A potentiostat featuring an integrator transimpedance amplifier for the
      measurement of very low currents--Proof-of-principle application in microfluidic
      separations and voltammetry.
AB  - This work reports the design and construction of a novel potentiostat which
      features an integrator transimpedance amplifier as a current-monitoring unit. The
      integration approach addresses the limitations of the feedback resistor approach
      used for current monitoring in conventional potentiostat designs. In the present
      design, measurement of the current is performed by a precision switched
      integrator transimpedance amplifier operated in the dual sampling mode which
      enables sub-pA resolution. The potentiostat is suitable for measuring very low
      currents (typical dynamic range: 5 pA-4.7 MUA) with a 16 bit resolution, and it
      can support 2-, 3- and 4-electrode cell configurations. Its operation was
      assessed by using it as a detection module in a home-made capillary
      electrophoresis system for the separation and amperometric detection of
      paracetamol and p-aminophenol at a 3-electrode microfluidic chip. The potential
      and limitations of the proposed potentiostat to implement fast potential-scan
      voltammetric techniques were demonstrated for the case of cyclic voltammetry. 

PMID- 27036789
TI  - Opto-electrochemical spectroscopy of metals in aqueous solutions.
AB  - In the present investigation, holographic interferometry was utilized for the
      first time to determine the rate change of the electrical resistance of aluminium
      samples during the initial stage of anodisation processes in aqueous solution. In
      fact, because the resistance values in this investigation were obtained by
      holographic interferometry, electromagnetic method rather than electronic method,
      the abrupt rate change of the resistance was called electrical resistance
      emission spectroscopy. The anodisation process of the aluminium samples was
      carried out by electrochemical impedance spectroscopy (EIS) in different
      sulphuric acid concentrations (1.0%-2.5% H2SO4) at room temperature. In the
      meantime, the real time holographic interferometry was used to determine the
      difference between the electrical resistance of two subsequent values, dR, as a
      function of the elapsed time of the EIS experiment for the aluminium samples in
      1.0%, 1.5%, 2.0%, and 2.5% H2SO4 solutions. The electrical resistance-emission
      spectra of the present investigation represent a detailed picture of not only the
      rate change of the electrical resistance throughout the anodisation processes but
      also the spectra represent the rate change of the growth of the oxide films on
      the aluminium samples in different solutions. As a result, a new spectrometer was
      developed based on the combination of the holographic interferometry and
      electrochemical impedance spectroscopy for studying in situ the electrochemical
      behavior of metals in aqueous solutions. 

PMID- 27036790
TI  - High yield, single crystal ice via the Bridgman method.
AB  - The surface chemistry of ice and of water is an important topic of study,
      especially given the role of ice and water in shaping the environment. Although
      snow, granular, and polycrystalline ice are often used in research, there are
      applications where large surface areas of a known crystallographic plane are
      required. For example, fundamental spectroscopy or scattering studies rely on
      large area samples of known crystalline orientation. In addition, due to its
      slower dynamics and decreased number of molecular configurations, ice can be
      viewed as a reduced complexity model for the complex hydrogen bonding environment
      found at the surface and within the bulk of liquid water. In our studies using
      Sum Frequency Generation (SFG) vibrational spectroscopy, we have shown that each
      crystalline face has a unique spectral signature and therefore a unique chemistry
      and chemical activity. A reliable, reproducible, high performance method of
      producing large single crystal samples is needed to support this surface
      chemistry research. The design, construction, and use of a computer-controlled,
      ice-growth machine based on the Stockbarger modified Bridgeman technique is
      described. The instrument reliably produces relatively large single crystals that
      are optically flawless (that is, no visible flaws when viewed in a crossed
      polarizer), and in very high yield. Success rates of 95% are typical. Such
      performance has not been observed in the literature. 

PMID- 27036792
TI  - Dose controlled low energy electron irradiator for biomolecular films.
AB  - We have developed a multi target, Low Energy Electron (LEE), precise dose
      controlled irradiator for biomolecular films. Up to seven samples can be
      irradiated one after another at any preset electron energy and dose under UHV
      conditions without venting the chamber. In addition, one more sample goes through
      all the steps except irradiation, which can be used as control for comparison
      with the irradiated samples. All the samples are protected against stray electron
      irradiation by biasing them at -20 V during the entire period, except during
      irradiation. Ethernet based communication electronics hardware, LEE beam control
      electronics and computer interface were developed in house. The user Graphical
      User Interface to control the irradiation and dose measurement was developed
      using National Instruments Lab Windows CVI. The working and reliability of the
      dose controlled irradiator has been fully tested over the electron energy range
      of 0.5 to 500 eV by studying LEE induced single strand breaks to PhiX174 RF1
      dsDNA. 

PMID- 27036791
TI  - Live cell imaging combined with high-energy single-ion microbeam.
AB  - DNA strand breaks can lead to cell carcinogenesis or cell death if not repaired
      rapidly and efficiently. An online live cell imaging system was established at
      the high energy microbeam facility at the Institute of Modern Physics to study
      early and fast cellular response to DNA damage after high linear energy transfer
      ion radiation. The HT1080 cells expressing XRCC1-RFP were irradiated with single
      high energy nickel ions, and time-lapse images of the irradiated cells were
      obtained online. The live cell imaging analysis shows that strand-break repair
      protein XRCC1 was recruited to the ion hit position within 20 s in the cells and
      formed bright foci in the cell nucleus. The fast recruitment of XRCC1 at the ion
      hits reached a maximum at about 200 s post-irradiation and then was followed by a
      slower release into the nucleoplasm. The measured dual-exponential kinetics of
      XRCC1 protein are consistent with the proposed consecutive reaction model, and
      the measurements obtained that the reaction rate constant of the XRCC1
      recruitment to DNA strand break is 1.2 * 10(-3) s(-1) and the reaction rate
      constant of the XRCC1 release from the break-XRCC1 complex is 1.2 * 10(-2) s(-1).

PMID- 27036793
TI  - Characterization of the room temperature payload prototype for the cryogenic
      interferometric gravitational wave detector KAGRA.
AB  - KAGRA is a cryogenic interferometric gravitational wave detector currently under
      construction in the Kamioka mine in Japan. Besides the cryogenic test masses,
      KAGRA will also rely on room temperature optics which will hang at the bottom of
      vibration isolation chains. The payload of each chain comprises an optic, a
      system to align it, and an active feedback system to damp the resonant motion of
      the suspension itself. This article describes the performance of a payload
      prototype that was assembled and tested in vacuum at the TAMA300 site at the NAOJ
      in Mitaka, Tokyo. We describe the mechanical components of the payload prototype
      and their functionality. A description of the active components of the feedback
      system and their capabilities is also given. The performance of the active system
      is illustrated by measuring the quality factors of some of the resonances of the
      suspension. Finally, the alignment capabilities offered by the payload are
      reported. 

PMID- 27036794
TI  - Comparing a new laser strainmeter array with an adjacent, parallel running quartz
      tube strainmeter array.
AB  - In summer 2011, two new laser strainmeters about 26.6 m long were installed in N
      S and E-W directions parallel to an existing quartz tube strainmeter system at
      the Geodynamic Observatory Moxa, Thuringia/Germany. This kind of installation is
      unique in the world and allows the direct comparison of measurements of
      horizontal length changes with different types of strainmeters for the first
      time. For the comparison of both data sets, we used the tidal analysis over three
      years, the strain signals resulting from drilling a shallow 100 m deep borehole
      on the ground of the observatory and long-period signals. The tidal strain
      amplitude factors of the laser strainmeters are found to be much closer to
      theoretical values (85%-105% N-S and 56%-92% E-W) than those of the quartz tube
      strainmeters. A first data analysis shows that the new laser strainmeters are
      more sensitive in the short-periodic range with an improved signal-to-noise ratio
      and distinctly more stable during long-term drifts of environmental parameters
      such as air pressure or groundwater level. We compared the signal amplitudes of
      both strainmeter systems at variable signal periods and found frequency-dependent
      amplitude differences. Confirmed by the tidal parameters, we have now a stable
      and high resolution laser strainmeter system that serves as calibration reference
      for quartz tube strainmeters. 

PMID- 27036795
TI  - Interaction between two adjacent grounded sources in frequency domain semi
      airborne electromagnetic survey.
AB  - Multi-source and multi-frequency emission method can make full use of the
      valuable and short flight time in frequency domain semi-airborne electromagnetic
      (FSAEM) exploration, which has potential to investigate the deep earth structure
      in complex terrain region. Because several sources are adjacent in multi-source
      emission method, the interaction of different sources should be considered
      carefully. An equivalent circuit model of dual-source is established in this
      paper to assess the interaction between two individual sources, where the
      parameters are given with the typical values based on the practical instrument
      system and its application. By simulating the output current of two sources in
      different cases, the influence from the adjacent source is observed clearly. The
      current waveforms show that the mutual resistance causes the fluctuation and
      drift in another source and that the mutual inductance causes transient peaks. A
      field test with dual-source was conducted to certify the existence of interaction
      between adjacent sources. The simulation of output current also shows that
      current errors at low frequency are mainly caused by the mutual resistance while
      those at high frequency are mainly due to the mutual inductance. Increasing the
      distance between neighboring sources is a proposed measure to reduce the emission
      signal errors with designed ones. The feasible distance is discussed in the end.
      This study gives a useful guidance to lay multi sources to meet the requirement
      of measurement accuracy in FSAEM survey. 

PMID- 27036796
TI  - Research on supporting mounts of spheres in measurement of gravitational constant
      G.
AB  - The ongoing precision measurement of the gravitational constant G at our group is
      performed by using two different kinds of methods: time-of-swing method (ToS) and
      angular acceleration feedback method. In the two methods, the stainless steel
      spheres are employed as source masses, and the position stability of the spheres
      is an important parameter, which make suitable mounts for supporting the spheres
      needed extremely. In this paper, an upgraded three-point mount is introduced and
      tested in detail. Experimental results show that, for the sphere supported by the
      three-point mount used in the ToS method, the repeatability, the temperature
      influence, and the vibration influence are all less than 0.1 MUm (about 2 ppm for
      the value of G). For the sphere supported by the three-point mount used in the
      AAF method, similar results are obtained, the largest change of the sphere's
      position is about 0.6 MUm, introduced by a temperature change of 1  degrees C,
      which also results in an uncertainty of 2 ppm for the value of G. 

PMID- 27036797
TI  - Analytical and experimental investigation of electrical characteristics of a
      metallic insulation GdBCO coil.
AB  - This paper presents results, experimental and analytical, of the electrical
      characteristics of GdBCO single-pancake coils co-wound with a brass tape as
      metallic insulation (MI coil). The GdBCO pancakes were subjected to sudden
      discharge, charge-discharge, and over-current tests. The sudden discharge and
      charge-discharge test results of the MI coil demonstrated that MI coils can be
      charged and discharged significantly faster than non-insulated coils that are
      wound only with GdBCO tape. In over-current tests at 150 A (1.25I(c)), the MI
      coil exhibited better electrical behavior, i.e., self-protecting features, than
      its counterpart co-wound with Kapton tape, an insulator. Moreover, the
      experimental and analytical results are in agreement, validating the use of a
      concise equivalent parallel-RL circuit model for the MI coil to characterize its
      electrical behavior. Overall, the MI winding technique is highly promising to
      help build compact, mechanically robust, and self-protecting magnets composed of
      REBCO pancake coils. With no organic material in the winding, MI REBCO pancakes
      will be immune to neutron radiation damage, making the MI winding technique a
      viable option for fusion reactors, such as for toroidal field, poroidal field
      magnets, and central solenoid.

PMID- 27036798
TI  - Modified sparse regularization for electrical impedance tomography.
AB  - Electrical impedance tomography (EIT) aims to estimate the electrical properties
      at the interior of an object from current-voltage measurements on its boundary.
      It has been widely investigated due to its advantages of low cost, non-radiation,
      non-invasiveness, and high speed. Image reconstruction of EIT is a nonlinear and
      ill-posed inverse problem. Therefore, regularization techniques like Tikhonov
      regularization are used to solve the inverse problem. A sparse regularization
      based on L1 norm exhibits superiority in preserving boundary information at sharp
      changes or discontinuous areas in the image. However, the limitation of sparse
      regularization lies in the time consumption for solving the problem. In order to
      further improve the calculation speed of sparse regularization, a modified method
      based on separable approximation algorithm is proposed by using adaptive step
      size and preconditioning technique. Both simulation and experimental results show
      the effectiveness of the proposed method in improving the image quality and real
      time performance in the presence of different noise intensities and conductivity
      contrasts. 

PMID- 27036799
TI  - Dual polarized receiving steering antenna array for measurement of ultrawideband
      pulse polarization structure.
AB  - To measure simultaneously two orthogonal components of the electromagnetic field
      of nano- and subnano-second duration, an antenna array has been developed. The
      antenna elements of the array are the crossed dipoles of dimension 5 * 5 cm. The
      arms of the dipoles are connected to the active four-pole devices to compensate
      the frequency response variations of a short dipole in the frequency band ranging
      from 0.4 to 4 GHz. The dipoles have superimposed phase centers allowing measuring
      the polarization structure of the field in different directions. The developed
      antenna array is the linear one containing four elements. The pattern maximum
      position is controlled by means of the switched ultrawideband true time delay
      lines. Discrete steering in seven directions in the range from -40 degrees  to
      +40 degrees  has been realized. The error at setting the pattern maximum position
      is less than 4 degrees . The isolation of the polarization exceeds 29 dB in the
      direction orthogonal to the array axis and in the whole steering range it exceeds
      23 dB. Measurement results of the polarization structure of radiated and
      scattered pulses with different polarization are presented as well. 

PMID- 27036800
TI  - Hyperbolic-cosine waveguide tapers and oversize rectangular waveguide for reduced
      broadband insertion loss in W-band electron paramagnetic resonance spectroscopy.
      II. Broadband characterization.
AB  - Experimental results have been reported on an oversize rectangular waveguide
      assembly operating nominally at 94 GHz. It was formed using commercially
      available WR28 waveguide as well as a pair of specially designed tapers with a
      hyperbolic-cosine shape from WR28 to WR10 waveguide [R. R. Mett et al., Rev. Sci.
      Instrum. 82, 074704 (2011)]. The oversize section reduces broadband insertion
      loss for an Electron Paramagnetic Resonance (EPR) probe placed in a 3.36 T
      magnet. Hyperbolic-cosine tapers minimize reflection of the main mode and the
      excitation of unwanted propagating waveguide modes. Oversize waveguide is
      distinguished from corrugated waveguide, overmoded waveguide, or quasi-optic
      techniques by minimal coupling to higher-order modes. Only the TE10 mode of the
      parent WR10 waveguide is propagated. In the present work, a new oversize assembly
      with a gradual 90 degrees  twist was implemented. Microwave power measurements
      show that the twisted oversize waveguide assembly reduces the power loss in the
      observe and pump arms of a W-band bridge by an average of 2.35 dB and 2.41 dB,
      respectively, over a measured 1.25 GHz bandwidth relative to a straight length of
      WR10 waveguide. Network analyzer measurements confirm a decrease in insertion
      loss of 2.37 dB over a 4 GHz bandwidth and show minimal amplitude distortion of
      approximately 0.15 dB. Continuous wave EPR experiments confirm these results. The
      measured phase variations of the twisted oversize waveguide assembly, relative to
      an ideal distortionless transmission line, are reduced by a factor of two
      compared to a straight length of WR10 waveguide. Oversize waveguide with proper
      transitions is demonstrated as an effective way to increase incident power and
      the return signal for broadband EPR experiments. Detailed performance
      characteristics, including continuous wave experiment using 1 MUM 2,2,6,6
      tetramethylpiperidine-1-oxyl in aqueous solution, provided here serve as a
      benchmark for other broadband low-loss probes in millimeter-wave EPR bridges. 

PMID- 27036801
TI  - Minimization of nanosatellite low frequency magnetic fields.
AB  - Small weight and dimensions of the micro- and nanosatellites constrain
      researchers to place electromagnetic sensors on short booms or on the satellite
      body. Therefore the electromagnetic cleanliness of such satellites becomes a
      central question. This paper describes the theoretical base and practical
      techniques for determining the parameters of DC and very low frequency magnetic
      interference sources. One of such sources is satellite magnetization, the
      reduction of which improves the accuracy and stability of the attitude control
      system. We present design solutions for magnetically clean spacecraft, testing
      equipment, and technology for magnetic moment measurements, which are more
      convenient, efficient, and accurate than the conventional ones. 

PMID- 27036802
TI  - Investigation of a stripline transmission line structure for gyromagnetic
      nonlinear transmission line high power microwave sources.
AB  - A stripline gyromagnetic nonlinear transmission line (NLTL) was constructed out
      of yttrium iron garnet ferrite and tested at charge voltages of 35 kV-55 kV with
      bias fields ranging from 10 kA/m to 20 kA/m. Typically, high power gyromagnetic
      NLTLs are constructed in a coaxial geometry. While this approach has many
      advantages, including a uniform transverse electromagnetic (TEM) mode, simple
      interconnection between components, and the ability to use oil or pressurized gas
      as an insulator, the coaxial implementation suffers from complexity of
      construction, especially when using a solid insulator. By moving to a simpler
      transmission line geometry, NLTLs can be constructed more easily and arrayed on a
      single substrate. This work represents a first step in exploring the suitability
      of various transmission line structures, such as microstrips and coplanar
      waveguides. The resulting high power microwave (HPM) source operates in ultra
      high frequency (UHF) band with an average bandwidth of 40.1% and peak rf power
      from 2 MW to 12.7 MW. 

PMID- 27036803
TI  - Bipolar square-wave current source for transient electromagnetic systems based on
      constant shutdown time.
AB  - Cooperative work of multiple magnetic transmitting sources is a new trend in the
      development of transient electromagnetic system. The key is the bipolar current
      waves shutdown, concurrently in the inductive load. In the past, it was difficult
      to use the constant clamping voltage technique to realize the synchronized
      shutdown of currents with different peak values. Based on clamping voltage
      technique, we introduce a new controlling method with constant shutdown time. We
      use the rising time to control shutdown time and use low voltage power source to
      control peak current. From the viewpoint of the circuit energy loss, by taking
      the high-voltage capacitor bypass resistance and the capacitor of the passive
      snubber circuit into account, we establish the relationship between the rising
      time and the shutdown time. Since the switch is not ideal, we propose a new
      method to test the shutdown time by the low voltage, the high voltage and the
      peak current. Experimental results show that adjustment of the current rising
      time can precisely control the value of the clamp voltage. When the rising time
      is fixed, the shutdown time is unchanged. The error for shutdown time deduced
      from the energy consumption is less than 6%. The new controlling method on
      current shutdown proposed in this paper can be used in the cooperative work of
      borehole and ground transmitting system. 

PMID- 27036804
TI  - Cross-spectrum measurement of thermal-noise limited oscillators.
AB  - Cross-spectrum analysis is a commonly used technique for the detection of phase
      and amplitude noise of a signal in the presence of interfering uncorrelated
      noise. Recently, we demonstrated that the phase-inversion (anti-correlation)
      effect due to amplitude noise leakage can cause complete or partial collapse of
      the cross-spectral function. In this paper, we discuss the newly discovered
      effect of anti-correlated thermal noise that originates from the common-mode
      power divider (splitter), an essential component in a cross-spectrum noise
      measurement system. We studied this effect for different power splitters and
      discuss its influence on the measurement of thermal-noise limited oscillators. We
      provide theory, simulation and experimental results. In addition, we expand this
      study to reveal how the presence of ferrite-isolators and amplifiers at the
      output ports of the power splitters can affect the oscillator noise measurements.
      Finally, we discuss a possible solution to overcome this problem. 

PMID- 27036805
TI  - Development of a compact generator for gigawatt, nanosecond high-voltage pulses.
AB  - A compact generator producing 2.2-ns 1.5 GW high-voltage pulses was developed.
      The generator employed a 27.6 Omega, 0.9 ns pulse-forming-line (PFL), which was
      charged by an iron core transformer with a turn ratio of 2:33.5 and a coefficient
      of 0.94. A 1.2 MUF, 20 kV capacitor and a hydrogen thyratron were used in the
      primary circuit. When the thyratron closed at 14.5 kV, 3.4% of the energy stored
      in the capacitor was delivered to the PFL in 850 ns, producing a peak voltage of
      up to ~500 kV. In addition, the principle of triple resonance transformation was
      employed by adding a 50 pF tuning capacitor and a 1.15 mH inductor between the
      transformer and the PFL, which led to a significant reduction of the duration and
      peak value of the transformer voltage without reducing that in the PFL.
      Meanwhile, an adjustable self-break oil switch was applied. By using transmission
      lines with impedance overmatched to that of the PFL, the generator delivered a
      512 kV pulse across an electron beam diode, generating radiation with a dose of
      20 mR/pulse at 20 cm ahead of the diode. The generator provides an excellent
      ultra-short radiation pulse source for the studies on radiation physics. 

PMID- 27036806
TI  - High-pressure differential scanning microcalorimeter.
AB  - A differential scanning microcalorimeter for studying thermotropic conformational
      transitions of biopolymers at high pressure has been designed. The calorimeter
      allows taking measurements of partial heat capacity of biopolymer solutions vs.
      temperature at pressures up to 3000 atm. The principles of operation of the
      device, methods of its calibration, as well as possible applications are
      discussed. 

PMID- 27036807
TI  - Design and characterization of a microelectromechanical system electro-thermal
      linear motor with interlock mechanism for micro manipulators.
AB  - The design, fabrication, and testing of a novel electro-thermal linear motor for
      micro manipulators is presented in this paper. The V-shape electro-thermal
      actuator arrays, micro lever, micro spring, and slider are introduced. In moving
      operation, the linear motor can move nearly 1 mm displacement with 100 MUm each
      step while keeping the applied voltage as low as 17 V. In holding operation, the
      motor can stay in one particular position without consuming energy and no creep
      deformation is found. Actuation force of 12.7 mN indicates the high force
      generation capability of the device. Experiments of lifetime show that the device
      can wear over two million cycles of operation. A silicon-on-insulator wafer is
      introduced to fabricate a high aspect ratio structure and the chip size is 8.5 mm
      * 8.5 mm * 0.5 mm. 

PMID- 27036808
TI  - A generalized Prandtl-Ishlinskii model for characterizing the rate-independent
      and rate-dependent hysteresis of piezoelectric actuators.
AB  - In this paper, a generalized hysteresis model is developed to describe both rate
      independent and rate-dependent hysteresis in piezoelectric actuators. Based on
      the classical Prandtl-Ishlinskii (P-I) model, the developed model adds a
      quadratic polynomial and makes other small changes. When it is used to describe
      rate-independent hysteresis, the parameters of the model are constants, which can
      be identified by self-adaptive particle swarm optimization. The effectiveness of
      this rate-independent modified P-I model is demonstrated by comparing simulation
      results of the developed model and the classic Prandtl-Ishlinskii model.
      Simulation results suggest that the rate-independent modified P-I model can
      describe hysteresis more precisely. Compared with the classical P-I model, the
      rate-independent modified P-I model reduces modeling error by more than 50%. When
      it is used to describe rate-independent hysteresis, a one-side operator is
      adopted and the parameters are functions with input frequency. The results of the
      experiments and simulations have shown that the proposed models can accurately
      describe both rate-independent and rate-dependent hysteresis in piezoelectric
      actuators. 

PMID- 27036809
TI  - Evaluation of peristaltic micromixers for highly integrated microfluidic systems.
AB  - Microfluidic devices based on the multilayer soft lithography allow accurate
      manipulation of liquids, handling reagents at the sub-nanoliter level, and
      performing multiple reactions in parallel processors by adapting micromixers.
      Here, we have experimentally evaluated and compared several designs of
      micromixers and operating conditions to find design guidelines for the
      micromixers. We tested circular, triangular, and rectangular mixing loops and
      measured mixing performance according to the position and the width of the valves
      that drive nanoliters of fluids in the micrometer scale mixing loop. We found
      that the rectangular mixer is best for the applications of highly integrated
      microfluidic platforms in terms of the mixing performance and the space
      utilization. This study provides an improved understanding of the flow behaviors
      inside micromixers and design guidelines for micromixers that are critical to
      build higher order fluidic systems for the complicated parallel bio/chemical
      processes on a chip. 

PMID- 27036810
TI  - Unscented transform-based uncertainty analysis of rotating coil transducers for
      field mapping.
AB  - The uncertainty of a rotating coil transducer for magnetic field mapping is
      analyzed. Unscented transform and statistical design of experiments are combined
      to determine magnetic field expectation, standard uncertainty, and separate
      contributions of the uncertainty sources. For nonlinear measurement models, the
      unscented transform-based approach is more error-proof than the linearization
      underlying the "Guide to the expression of Uncertainty in Measurements" (GUMs),
      owing to the absence of model approximations and derivatives computation. When
      GUM assumptions are not met, the deterministic sampling strategy strongly reduces
      computational burden with respect to Monte Carlo-based methods proposed by the
      Supplement 1 of the GUM. Furthermore, the design of experiments and the
      associated statistical analysis allow the uncertainty sources domain to be
      explored efficiently, as well as their significance and single contributions to
      be assessed for an effective setup configuration. A straightforward experimental
      case study highlights that a one-order-of-magnitude reduction in the relative
      uncertainty of the coil area produces a decrease in uncertainty of the field
      mapping transducer by a factor of 25 with respect to the worst condition.
      Moreover, about 700 trials and the related processing achieve results
      corresponding to 5 * 10(6) brute-force Monte Carlo simulations. 

PMID- 27036811
TI  - Crack detection and monitoring in viscoelastic solids using polymer optical fiber
      sensors.
AB  - Detecting and monitoring of crack in viscoelastic solids, as a result of large
      and time-dependent deformations, are of great importance but have not been
      carried out sufficiently well. In this paper, polymer optical fibers (POFs) are
      employed to detect and monitor cracks in viscoelastic solids subjected to tensile
      loading. The sensor system is developed based on the variation of light intensity
      within the POFs when the POF sensors are loaded. The sensors show good stability,
      cost-effective, and large enough strain range (60%). The results demonstrate that
      in addition to monitoring the strain state of viscoelastic solids, the POFs
      strain sensors can detect initial cracks and monitor cracks propagation up to
      ultimate failure. 

PMID- 27036812
TI  - High precision relative attitude measurement for inner payload of new
      photoelectric platform.
AB  - A new method for measuring the relative attitude of a load on an airborne
      photoelectric platform supported by three-axis universal joint structure is
      proposed. The mathematical model for angle measurement is established, based on
      which the linear relation between the angle and distance is derived by using the
      eccentric method. Furthermore, the relative attitude measurement method for a
      load rotating along the yaw and pitch directions is also proposed based on a
      unique eccentric structure. Finally, to validate the proposed new method, a
      comprehensive experiment for measurement angle from -5 degrees  to +5 degrees  in
      increments of 0.5 degrees  was performed by using the angular capacitive sensor.
      The experimental results show that the precision of the angular measurement is
      better than 15" with maximum 1.24 kHz bandwidth, which meets the relative
      attitude measurement requirements of the internal load on the airborne
      photoelectric platform. 

PMID- 27036813
TI  - Measurement of inkjet first-drop behavior using a high-speed camera.
AB  - Drop-on-demand inkjet printing has been used as a manufacturing tool for printed
      electronics, and it has several advantages since a droplet of an exact amount can
      be deposited on an exact location. Such technology requires positioning the
      inkjet head on the printing location without jetting, so a jetting pause (non
      jetting) idle time is required. Nevertheless, the behavior of the first few drops
      after the non-jetting pause time is well known to be possibly different from that
      which occurs in the steady state. The abnormal behavior of the first few drops
      may result in serious problems regarding printing quality. Therefore, a proper
      evaluation of a first-droplet failure has become important for the inkjet
      industry. To this end, in this study, we propose the use of a high-speed camera
      to evaluate first-drop dissimilarity. For this purpose, the image acquisition
      frame rate was determined to be an integer multiple of the jetting frequency, and
      in this manner, we can directly compare the droplet locations of each drop in
      order to characterize the first-drop behavior. Finally, we evaluate the effect of
      a sub-driving voltage during the non-jetting pause time to effectively suppress
      the first-drop dissimilarity. 

PMID- 27036814
TI  - A novel calibration method for non-orthogonal shaft laser theodolite measurement
      system.
AB  - Non-orthogonal shaft laser theodolite (N-theodolite) is a new kind of large-scale
      metrological instrument made up by two rotary tables and one collimated laser.
      There are three axes for an N-theodolite. According to naming conventions in
      traditional theodolite, rotary axes of two rotary tables are called as horizontal
      axis and vertical axis, respectively, and the collimated laser beam is named as
      sight axis. And the difference between N-theodolite and traditional theodolite is
      obvious, since the former one with no orthogonal and intersecting accuracy
      requirements. So the calibration method for traditional theodolite is no longer
      suitable for N-theodolite, while the calibration method applied currently is
      really complicated. Thus this paper introduces a novel calibration method for non
      orthogonal shaft laser theodolite measurement system to simplify the procedure
      and to improve the calibration accuracy. A simple two-step process, calibration
      for intrinsic parameters and for extrinsic parameters, is proposed by the novel
      method. And experiments have shown its efficiency and accuracy. 

PMID- 27036815
TI  - A fully enclosed, compact standard lightning impulse generator for testing ultra
      high-voltage-class gas-insulated switchgears with high capacitance.
AB  - At present, conducting standard lightning impulse (LI) tests in the field for gas
      insulated switchgear (GIS) equipment is difficult because of the high capacitance
      of the test equipment and large circuit inductance of traditional impulse
      devices, which leads to a wavefront time T(f) >= 2.5 MUs. A novel fully enclosed,
      compact standard LI generator for testing ultra-high-voltage-class GIS equipment
      with high capacitance is presented to solve the problem of T(f) exceeding the
      standard during LI voltage tests for actual large-sized equipment. The impulse
      generator is installed in a metal vessel filled with SF6 or SF6/N2 gas mixture at
      a pressure of 0.3-0.5 MPa, providing a more compact structure and a lower series
      inductance. A newly developed conical voltage sensor is used to accurately
      measure the output voltage waveform. Two test modes (via bushing docking and
      direct docking) for the GIS test based on the impulse generator are introduced.
      Calculation results show that the impulse generator can generate an LI test
      waveform following the present IEC standard for the test of equipment with
      capacitance >10,000 pF.

PMID- 27036816
TI  - Deployment shock attenuation of a solar array tape hinge by means of the
      Martensite detwinning of NiTi Shape Memory Alloy.
AB  - This paper presents a new tape hinge for attenuating the deployment shock of a
      satellite solar array. This hinge uses the Martensite detwinning of Shape Memory
      Alloy (SMA). To attenuate the deployment shock, a NiTi SMA strip is assembled
      between two curved steel strips. The attenuation performance of the hinge is
      analyzed using a SMA detwinning constitutive equation. A prototype of the hinge
      is manufactured and its characteristics are measured in a bending test and in a
      deployment test. Finally, the deployment performance of the prototype hinge is
      investigated on a satellite model. It is shown that the new SMA damped tape hinge
      can effectively minimize the deployment shock and dynamic perturbation while also
      maintaining suitable deployment performance. 

PMID- 27036817
TI  - A directional cylindrical anemometer with four sets of differential pressure
      sensors.
AB  - This paper presents a solid-state directional anemometer for simultaneously
      measuring the speed and direction of a wind in a plane in a speed range 1-40 m/s.
      This instrument has a cylindrical shape and works by detecting the pressure
      differences across diameters of the cylinder when exposed to wind. By analyzing
      our experimental data in a Reynolds number regime 1.7 * 10(3)-7 * 10(4), we
      figure out the relationship between the pressure difference distribution and the
      wind velocity. We propose a novel and simple solution based on the relationship
      and design an anemometer which composes of a circular cylinder with four sets of
      differential pressure sensors, tubes connecting these sensors with the cylinder's
      surface, and corresponding circuits. In absence of moving parts, this instrument
      is small and immune of friction. It has simple internal structures, and the
      fragile sensing elements are well protected. Prototypes have been fabricated to
      estimate performance of proposed approach. The power consumption of the prototype
      is less than 0.5 W, and the sample rate is up to 31 Hz. The test results in a
      wind tunnel indicate that the maximum relative speed measuring error is 5% and
      the direction error is no more than 5 degrees  in a speed range 2-40 m/s. In
      theory, it is capable of measuring wind up to 60 m/s. When the air stream goes
      slower than 2 m/s, the measuring errors of directions are slightly greater, and
      the performance of speed measuring degrades but remains in an acceptable range of
      +/-0.2 m/s. 

PMID- 27036818
TI  - Fully variable elliptical phase retarder composed of two linear phase retarders.
AB  - In this study, a fully variable elliptical phase retarder was developed by
      combining a variable linear phase retarder and a half-wave plate. All three
      polarization parameters of the elliptical phase retarder (elliptical phase
      retardation gamma, azimuth angle theta, and ellipticity angle epsilon) were
      adjustable. Experimental verification was performed by measuring the polarization
      parameters with a polarizer-sample-analyzer polarimeter. The polarization
      parameters were set to gamma = 120 degrees , epsilon = 15 degrees , and theta =
      20 degrees . The measurement results, gamma = 119.838 degrees  +/- 0.006 degrees
      , epsilon = 14.659 degrees  +/- 0.002 degrees , and theta = 20.084 degrees  +/-
      0.002 degrees , agreed with theoretical prediction. 

PMID- 27036819
TI  - Demonstration of a time-resolved x-ray scattering instrument utilizing the full
      repetition rate of x-ray pulses at the Pohang Light Source.
AB  - We report on the development of a new experimental instrument for time-resolved x
      ray scattering (TRXS) at the Pohang Light Source (PLS-II). It operates with a
      photon energy ranging from 5 to 18 keV. It is equipped with an amplified
      Ti:sappahire femtosecond laser, optical diagnostics, and laser beam delivery for
      pump-probe experiments. A high-speed single-element detector and high trigger
      rate oscilloscope are used for rapid data acquisition. While this instrument is
      capable of measuring sub-nanosecond dynamics using standard laser pump/x-ray
      probe techniques, it also takes advantage of the dense 500 MHz standard fill
      pattern in the PLS-II storage ring to efficiently record nano-to-micro-second
      dynamics simultaneously. We demonstrate this capability by measuring both the
      (fast) impulsive strain and (slower) thermal recovery dynamics of a crystalline
      InSb sample following intense ultrafast laser excitation. Exploiting the full
      repetition rate of the storage ring results in a significant improvement in data
      collection rates compared to conventional bunch-tagging methods. 

PMID- 27036820
TI  - A flexible setup for angle-resolved X-ray fluorescence spectrometry with
      laboratory sources.
AB  - X-ray fluorescence (XRF) analysis is one of the standard tools for the analysis
      of stratified materials and is widely applied for the investigation of
      electronics and coatings. The composition and thickness of the layers can be
      determined quantitatively and non-destructively. Recent work showed that these
      capabilities can be extended towards retrieving stratigraphic information like
      concentration depth profiles using angle-resolved XRF (ARXRF). This paper
      introduces an experimental sample chamber which was developed as a multi-purpose
      tool enabling different measurement geometries suited for transmission
      measurements, conventional XRF, ARXRF, etc. The chamber was specifically designed
      for attaching all kinds of laboratory X-ray sources for the soft and hard X-ray
      ranges as well as various detection systems. In detail, a setup for ARXRF using
      an X-ray tube with a polycapillary X-ray lens as source is presented. For such a
      type of setup, both the spectral and lateral characterizations of the radiation
      field are crucial for quantitative ARXRF measurements. The characterization is
      validated with the help of a stratified validation sample. 

PMID- 27036821
TI  - CAMEA--A novel multiplexing analyzer for neutron spectroscopy.
AB  - The analyzer detector system continuous angle multiple energy analysis will be
      installed on the cold-neutron triple-axis spectrometer RITA-2 at SINQ, PSI. CAMEA
      is optimized for efficiency in the horizontal scattering plane enabling rapid and
      detailed mapping of excitations. As a novelty the design employs a series of
      several sequential upward scattering analyzer arcs. Each arc is set to a
      different, fixed, final energy and scatters neutrons towards position sensitive
      detectors. Thus, neutrons with different final energies are recorded
      simultaneously over a large angular range. In a single data-acquisition many
      entire constant-energy lines in the horizontal scattering plane are recorded for
      a quasi-continuous angular coverage of about 60 degrees . With a large combined
      coverage in energy and momentum, this will result in a very efficient
      spectrometer, which will be particularly suited for parametric studies under
      extreme conditions with restrictive sample environments (high field magnets or
      pressure cells) and for small samples of novel materials. In this paper we
      outline the concept and the specifications of the instrument currently under
      construction. 

PMID- 27036822
TI  - Classification of weld defect based on information fusion technology for
      radiographic testing system.
AB  - Improving the efficiency and accuracy of weld defect classification is an
      important technical problem in developing the radiographic testing system. This
      paper proposes a novel weld defect classification method based on information
      fusion technology, Dempster-Shafer evidence theory. First, to characterize weld
      defects and improve the accuracy of their classification, 11 weld defect features
      were defined based on the sub-pixel level edges of radiographic images, four of
      which are presented for the first time in this paper. Second, we applied
      information fusion technology to combine different features for weld defect
      classification, including a mass function defined based on the weld defect
      feature information and the quartile-method-based calculation of standard weld
      defect class which is to solve a sample problem involving a limited number of
      training samples. A steam turbine weld defect classification case study is also
      presented herein to illustrate our technique. The results show that the proposed
      method can increase the correct classification rate with limited training samples
      and address the uncertainties associated with weld defect classification. 

PMID- 27036823
TI  - Design and optimization of a modular setup for measurements of three-dimensional
      spin polarization with ultrafast pulsed sources.
AB  - ULTRASPIN is an apparatus devoted to the measurement of the spin polarization
      (SP) of electrons ejected from solid surfaces in a UHV environment. It is
      designed to exploit ultrafast light sources (free electron laser or laser high
      harmonic generation) and to perform (photo)electron spin analysis by an
      arrangement of Mott scattering polarimeters that measure the full SP vector. The
      system consists of two interconnected UHV vessels: one for surface science sample
      cleaning treatments, e-beam deposition of ultrathin films, and low energy
      electron diffraction/AES characterization. The sample environment in the
      polarimeter allows for cryogenic cooling and in-operando application of electric
      and magnetic fields. The photoelectrons are collected by an electrostatic
      accelerator and transport lens that form a periaxial beam that is subsequently
      directed by a Y-shaped electrostatic deflector to either one of the two
      orthogonal Mott polarimeters. The apparatus has been designed to operate in the
      extreme conditions of ultraintense single-X-ray pulses as originated by free
      electron lasers (up to 1 kHz), but it allows also for the single electron
      counting mode suitable when using statistical sources such as synchrotron
      radiation, cw-laser, or e-gun beams (up to 150 kcps). 

PMID- 27036824
TI  - Improvement of immunoassay detection system by using alternating current magnetic
      susceptibility.
AB  - A major goal with this research was to develop a low-cost and highly sensitive
      immunoassay detection system by using alternating current (AC) magnetic
      susceptibility. We fabricated an improved prototype of our previously developed
      immunoassay detection system and evaluated its performance. The prototype
      continuously moved sample containers by using a magnetically shielded brushless
      motor, which passes between two anisotropic magneto resistance (AMR) sensors.
      These sensors detected the magnetic signal in the direction where each sample
      container passed them. We used the differential signal obtained from each AMR
      sensor's output to improve the signal-to-noise ratio (SNR) of the magnetic signal
      measurement. Biotin-conjugated polymer beads with avidin-coated magnetic
      particles were prepared to examine the calibration curve, which represents the
      relation between AC magnetic susceptibility change and polymer-bead
      concentration. For the calibration curve measurement, we, respectively, measured
      the magnetic signal caused by the magnetic particles by using each AMR sensor
      installed near the upper or lower part in the lateral position of the passing
      sample containers. As a result, the SNR of the prototype was 4.5 times better
      than that of our previous system. Moreover, the data obtained from each AMR
      sensor installed near the upper part in the lateral position of the passing
      sample containers exhibited an accurate calibration curve that represented good
      correlation between AC magnetic susceptibility change and polymer-bead
      concentration. The conclusion drawn from these findings is that our improved
      immunoassay detection system will enable a low-cost and highly sensitive
      immunoassay. 

PMID- 27036825
TI  - Quantum random flip-flop and its applications in random frequency synthesis and
      true random number generation.
AB  - In this work, a new type of elementary logic circuit, named random flip-flop
      (RFF), is proposed, experimentally realized, and studied. Unlike conventional
      Boolean logic circuits whose action is deterministic and highly reproducible, the
      action of a RFF is intentionally made maximally unpredictable and, in the
      proposed realization, derived from a fundamentally random process of emission and
      detection of light quanta. We demonstrate novel applications of RFF in randomness
      preserving frequency division, random frequency synthesis, and random number
      generation. Possible usages of these applications in the information and
      communication technology, cryptographic hardware, and testing equipment are
      discussed. 

PMID- 27036826
TI  - Time of flight spectrometer for background-free positron annihilation induced
      Auger electron spectroscopy.
AB  - We describe a novel spectrometer designed for positron annihilation induced Auger
      electron spectroscopy employing a time-of-flight spectrometer. The spectrometer's
      new configuration enables us to implant monoenergetic positrons with kinetic
      energies as low as 1.5 eV on the sample while simultaneously allowing for the
      detection of electrons emitted from the sample surface at kinetic energies
      ranging from ~500 eV to 0 eV. The spectrometer's unique characteristics made it
      possible to perform (a) first experiments demonstrating the direct transition of
      a positron from an unbound scattering state to a bound surface state and (b) the
      first experiments demonstrating that Auger electron spectra can be obtained down
      to 0 eV without the beam induced secondary electron background obscuring the low
      energy part of the spectra. Data are presented which show alternative means of
      estimating positron surface state binding energy and background-free Auger
      spectra. 

PMID- 27036827
TI  - Design and investigation of a multichannel laser-triggered vacuum switch.
AB  - A laser-triggered vacuum switch (LTVS) is an advanced closing switch with
      nanosecond delay and jitter. In order to enhance hold-off voltage and extend the
      service lifetime of an LTVS, we designed a multichannel laser-triggered vacuum
      switch (MLTVS) utilizing a cone-shaped target electrode placed on the cathode
      platform. The fabrication and testing of the MLTVS is described in this paper.
      Experimental results show that the working voltage of the MLTVS with a gap
      distance of 12 mm is from 30 V to 20 kV. The threshold energy for triggering the
      switch is 0.4 mJ corresponding to a peak power density of 27.9 MW/cm(2). The
      triggering lifetime of a spot can reach up to 18,000 shots. In addition, the
      relationship between triggering lifetime and target materials is analyzed using a
      field emission scanning electron microscope. A hypothesis of the vacuum gap's
      triggering mechanism is discussed based on the measured results.

PMID- 27036828
TI  - Work function measurements using a field emission retarding potential technique.
AB  - Herein we describe the measurement of the work function of a metal with advanced
      equipment based on the field emission retarding potential (FERP) method using a
      carbon nanotube (CNT) as cathode. The accuracy of the FERP method using a CNT
      emitter is described and a comparison between measurements of the work functions
      of aluminum, barium, calcium, gold, and platinum with published data will be
      presented. Our FERP equipment could be optimized with the aid of particle tracing
      simulations. These simulations led us to insert a magnetic collimator to improve
      the collection efficiency at the anode. 

PMID- 27036829
TI  - Indirect measurement of molten steel level in tundish based on laser
      triangulation.
AB  - For real-time and precise measurement of molten steel level in tundish during
      continuous casting, slag level and slag thickness are needed. Among which, the
      problem of slag thickness measurement has been solved in our previous work. In
      this paper, a systematic solution for slag level measurement based on laser
      triangulation is proposed. Being different from traditional laser triangulation,
      several aspects for measuring precision and robustness have been done. First,
      laser line is adopted for multi-position measurement to overcome the deficiency
      of single point laser range finder caused by the uneven surface of the slag.
      Second, the key parameters, such as installing angle and minimum requirement of
      the laser power, are analyzed and determined based on the gray-body radiation
      theory to fulfill the rigorous requirement of measurement accuracy. Third, two
      kinds of severe noises in the acquired images, which are, respectively, caused by
      heat radiation and Electro-Magnetic Interference (EMI), are cleaned via
      morphological characteristic of the liquid slag and color difference between EMI
      and the laser signals, respectively. Fourth, as false target created by
      stationary slag usually disorders the measurement, valid signals of the slag are
      distinguished from the false ones to calculate the slag level. Then, molten steel
      level is obtained by the slag level minus the slag thickness. The measuring error
      of this solution is verified by the applications in steel plants, which is +/-2.5
      mm during steady casting and +/-3.2 mm at the end of casting. 

PMID- 27036830
TI  - Characterization of a time-resolved non-contact scanning diffuse optical imaging
      system exploiting fast-gated single-photon avalanche diode detection.
AB  - We present a system for non-contact time-resolved diffuse reflectance imaging,
      based on small source-detector distance and high dynamic range measurements
      utilizing a fast-gated single-photon avalanche diode. The system is suitable for
      imaging of diffusive media without any contact with the sample and with a spatial
      resolution of about 1 cm at 1 cm depth. In order to objectively assess its
      performances, we adopted two standardized protocols developed for time-domain
      brain imagers. The related tests included the recording of the instrument
      response function of the setup and the responsivity of its detection system.
      Moreover, by using liquid turbid phantoms with absorbing inclusions, depth
      dependent contrast and contrast-to-noise ratio as well as lateral spatial
      resolution were measured. To illustrate the potentialities of the novel approach,
      the characteristics of the non-contact system are discussed and compared to those
      of a fiber-based brain imager. 

PMID- 27036831
TI  - TURBOGEN: Computer-controlled vertically oscillating grid system for small-scale
      turbulence studies on plankton.
AB  - In recent years, there has been a renewed interest in the impact of turbulence on
      aquatic organisms. In response to this interest, a novel instrument has been
      constructed, TURBOGEN, that generates turbulence in water volumes up to 13 l.
      TURBOGEN is fully computer controlled, thus, allowing for a high level of
      reproducibility and for variations of the intensity and characteristics of
      turbulence during the experiment. The calibration tests, carried out by particle
      image velocimetry, showed TURBOGEN to be successful in generating isotropic
      turbulence at the typical relatively low levels of the marine environment.
      TURBOGEN and its sizing have been devised with the long-term scope of analyzing
      in detail the molecular responses of plankton to different mixing regimes, which
      is of great importance in both environmental and biotechnological processes. 

PMID- 27036832
TI  - Mass separation of deuterium and helium with conventional quadrupole mass
      spectrometer by using varied ionization energy.
AB  - Deuterium pressure in deuterium-helium mixture gas is successfully measured by a
      common quadrupole mass spectrometer (model: RGA200) with a resolution of ~0.5
      atomic mass unit (AMU), by using varied ionization energy together with new
      developed software and dedicated calibration for RGA200. The new software is
      developed by using MATLAB with the new functions: electron energy (EE) scanning,
      deuterium partial pressure measurement, and automatic data saving. RGA200 with
      new software is calibrated in pure deuterium and pure helium 1.0 * 10(-6)-5.0 *
      10(-2) Pa, and the relation between pressure and ion current of AMU4 under EE =
      25 eV and EE = 70 eV is obtained. From the calibration result and RGA200 scanning
      with varied ionization energy in deuterium and helium mixture gas, both deuterium
      partial pressures (P(D2)) and helium partial pressure (P(He)) could be obtained.
      The result shows that deuterium partial pressure could be measured if P(D2) > 10(
      6) Pa (limited by ultimate pressure of calibration vessel), and helium pressure
      could be measured only if P(He)/P(D2) > 0.45, and the measurement error is
      evaluated as 15%. This method is successfully employed in EAST 2015 summer
      campaign to monitor deuterium outgassing/desorption during helium discharge
      cleaning.

PMID- 27036833
TI  - A fiber optic, ultraviolet light-emitting diode-based, two wavelength fluorometer
      for monitoring reactive adsorption.
AB  - Construction and use of an ultraviolet light-emitting diode-based fluorometer for
      measuring photoluminescence (PL) from powder samples with a fiber optic probe is
      described. Fluorescence at two wavelengths is detected by miniature
      photomultiplier tubes, each equipped with a different band pass filter, whose
      outputs are analyzed by a microprocessor. Photoluminescent metal oxides and
      hydroxides, and other semiconducting nanoparticles, often undergo changes in
      their emission spectra upon exposure to reactive gases, and the ratio of the PL
      intensities at two wavelengths is diagnostic of adsorption. Use of this
      instrument for reactive gas sensing and gas filtration applications is
      illustrated by measuring changes in the PL ratio for zirconium hydroxide and zinc
      oxide particles upon exposure to air containing low concentrations of sulfur
      dioxide. 

PMID- 27036834
TI  - Note: Molecular diffusivity in a small pore zeolite measured by a variable
      pressure (piezometric) uptake method.
AB  - The use of numerical analysis to solve the diffusion equation in the uptake
      method allowed the measurement of molecular diffusivity in a zeolite with a
      variable pressure around it. The diffusivity was obtained from the data in the
      measurement of the adsorption isotherm, which means that the diffusivity
      measurement now needs neither a special instrument nor procedure. The
      diffusivities of all the gases are readily available from the measurement of
      their adsorption isotherms and these data include how the diffusivity changes
      versus adsorbed concentration. The modeling introduced can also be used for a
      zeolite with a surface barrier. 

PMID- 27036835
TI  - Note: Moissanite backing plates for use in diamond anvil high pressure cells.
AB  - The use of moissanite (single crystal SiC) for backing plates within diamond
      anvil cells (DACs) has been developed. These have significant technical
      advantages in certain experiments. For example, moissanite is non-magnetic so is
      suitable for use in high magnetic fields and for magnetization experiments. Being
      translucent to light, including x-rays, means that openings are not required in
      the backing plate and as such has significant mechanical advantages and can
      provide enhanced scattering angles for x-ray diffraction experiments. The new
      backing plates have been successfully tested to over 25 GPa using diamond anvils
      with 0.5 mm culets. 

PMID- 27036836
TI  - Note: Simple and portable setup for loading high purity liquids in diamond anvil
      cell.
AB  - Here we explain a simple and inexpensive procedure to preserve the original
      purity of the liquid samples during the loading process in a diamond anvil cell.
      The idea is to keep the sample in frozen form during the loading process while
      preventing the condensation of the water or other introduction of contaminants.
      The system can be quickly and easily assembled in a basic laboratory setup. This
      process can be used for loading some of the common pressure media in a diamond
      anvil cell. 

PMID- 27036837
TI  - Note: On-chip multifunctional fluorescent-magnetic Janus helical microswimmers.
AB  - Microswimmers integrated into microfluidic devices that are capable of self
      illumination through fluorescence could revolutionize many aspects of technology,
      especially for biological applications. Few illumination and propulsion
      techniques of helical microswimmers inside microfluidic channels have been
      demonstrated. This paper presents the fabrication, detachment, and magnetic
      propulsions of multifunctional fluorescent-magnetic helical microswimmers
      integrated inside microfluidics. The fabrication process is based on two-photon
      laser lithography to pattern 3-D nanostructures from fluorescent photoresist
      coupled with conventional microfabrication techniques for magnetic thin film
      deposition by shadowing. After direct integration inside a microfluidic device,
      injected gas bubble allows gentle detachment of the integrated helical
      microswimmers whose magnetic propulsion can then be directly applied inside the
      microfluidic channel using external electromagnetic coil setup. With their small
      scale, fluorescence, excellent resistance to liquid/gas surface tension, and
      robust propulsion capability inside the microfluidic channel, the microswimmers
      can be used as high-resolution and large-range mobile micromanipulators inside
      microfluidic channels. 

PMID- 27036838
TI  - Note: High-power piezoelectric transformer fabricated with ternary relaxor
      ferroelectric Pb(Mg(1/3)Nb(2/3))O3-Pb(In(1/2)Nb(1/2))O3-PbTiO3 single crystal.
AB  - A plate-shaped piezoelectric transformer was designed and fabricated using
      ternary relaxor ferroelectric single crystal Pb(Mg(1/3)Nb(2/3))O3
      Pb(In(1/2)Nb(1/2))O3-PbTiO3. Both the input and output sections utilized the
      transverse-extensional vibration mode. The frequency and load dependences of the
      electrical properties for the proposed transformer were systematically studied.
      Results indicated that under a matching load resistance of 14.9 kOmega, a maximum
      output power of 2.56 W was obtained with the temperature rise less than 5 
      degrees C. The corresponding power density reached up to 50 W/cm(3). This ternary
      single-crystal transformer had potential applications in compact-size converters
      requiring high power density.

PMID- 27036839
TI  - Note: Enhancing the sensitivity of roll-angle measurement with a novel
      interferometric configuration based on waveplates and folding mirror.
AB  - A novel method for very high resolution measurement of roll angle on a
      transparent plate is developed theoretically and tested experimentally. The new
      optical configuration is based on the interferometric readout of phase shift
      accumulated on the double passage through half wave plate, together with a
      careful control of polarization state by means of quarter wave plate, and
      optimizing the tilt of the folding mirror. Sensitivity to roll angle is greatly
      enhanced and a gain coefficient exceeding 700 is found theoretically, based on
      Jones' matrix analysis, with a 6-fold increase respect to previous results. In
      the experimental setup, at the optimum 36 degrees  incidence to retroreflector,
      we measured a gain coefficient of 340. Correspondingly, with an interferometer
      phase meter resolving 0.01 degrees , a roll-angle resolution 0.1-arc sec is
      attained. 

PMID- 27036840
TI  - Note: Gaussian mixture model for event recognition in optical time-domain
      reflectometry based sensing systems.
AB  - We propose a novel approach to the recognition of particular classes of non
      conventional events in signals from phase-sensitive optical time-domain
      reflectometry-based sensors. Our algorithmic solution has two main features:
      filtering aimed at the de-nosing of signals and a Gaussian mixture model to
      cluster them. We test the proposed algorithm using experimentally measured
      signals. The results show that two classes of events can be distinguished with
      the best-case recognition probability close to 0.9 at sufficient numbers of
      training samples. 

PMID- 27036841
TI  - Note: Dynamic meso-scale full field surface deformation measurement of
      heterogeneous materials.
AB  - A dynamic experiment at mesoscale is developed to measure local deformation and
      strain in granular materials at high temporal and spatial resolutions. The
      experimental setup is comprised of a high-speed camera along with a high
      magnification extension tube. The method is demonstrated by measuring the full
      field strain across and in the boundary of the crystals at a high temporal
      resolution in polymer bonded sugar crystals and glass beads filled epoxy
      particulate composite specimens under dynamic loading. In both cases, the local
      strain heterogeneity is captured successfully. The measured strain and
      deformation field can be further used to obtain the relative motion of each
      crystal, crystal rotation, and the relative displacement between the polymer
      interface and the crystal, which are very critical to understand the local
      failure mechanisms in heterogeneous materials. 

PMID- 27036842
TI  - Note: Consecutive capture of images of ions and electrons using high-voltage
      vacuum relay.
AB  - For the first time, images of both ions and electrons appearing on a fluorescent
      screen attached to a micro-channel plate (MCP) [S. Nakata et al., "Applicability
      of micro-channel plate followed by phosphor screen to charged particles," Rev.
      Sci. Instrum. (submitted)] were captured in one attempt. The profile of
      electrostatic potential applied externally to the MCP with the fluorescent screen
      was quickly changed using a high-voltage vacuum relay. This method allows
      consecutive images of ions and electrons to be successfully captured. 

PMID- 27036843
TI  - Note: Automatic layer-by-layer spraying system for functional thin film coatings.
AB  - In this study, we have constructed an automatic spray machine for producing
      polyelectrolyte multilayer films containing various functional materials on wide
      substrates via the layer-by-layer (LbL) assembly technique. The proposed machine
      exhibits advantages in terms of automation, process speed, and versatility.
      Furthermore, it has several features that allow a fully automated spraying
      operation, such as various two-dimensional spraying paths, control of the flow
      rate and operating speed, air-assist fan-shaped twin-fluid nozzles, and an
      optical display. The robot uniformly sprays aqueous mixtures containing
      complementary (e.g., oppositely charged, capable of hydrogen bonding, or capable
      of covalent bonding) species onto a large-area substrate. Between each deposition
      of opposite species, samples are spray-rinsed with deionized water and blow-dried
      with air. The spraying, rinsing, and drying areas and times are adjustable by a
      computer program. Twenty-bilayer flame-retardant thin films were prepared in
      order to compare the performance of the spray-assisted LbL assembly with a sample
      produced by conventional dipping. The spray-coated film exhibited a reduction of
      afterglow time in vertical flame tests, indicating that the spray-LbL technique
      is a simple method to produce functional thin film coatings. 

PMID- 27036844
TI  - Note: Flow mediated skin fluorescence--A novel technique for evaluation of
      cutaneous microcirculation.
AB  - This note describes a newly developed technique for evaluation of cutaneous
      microcirculation. The technique called Flow Mediated Skin Fluorescence (FMSF) is
      based on monitoring of NADH fluorescence intensity emitted from the skin tissue
      cells of a forearm. The changes in fluorescence intensity as a function of time
      in response to blocking and releasing of blood flow in a forearm are used as a
      measure of oxygen transport with blood to the tissue, which directly correlates
      with the skin microcirculation status. Preliminary results collected for healthy
      volunteers and patients experiencing serious cardiovascular problems indicated a
      usefulness of FMSF technique for evaluation of health related perturbations in
      cutaneous microcirculation. 

PMID- 27036845
TI  - Note: Development of a compact aperture-type XYthetaz positioning stage.
AB  - In this paper, we propose a new in-plane XYthetaz nano-positioning stage that
      utilizes piezoelectric actuators and flexure mechanisms. The proposed stage has
      an aperture and is compact, which facilitates its application in measurement
      equipment, especially those used for biological specimens. The stage has four
      piezoelectric actuators and four bridge-type flexure mechanisms, which are used
      to amplify the small motions produced by the piezoelectric actuators. This paper
      describes the modeling and design optimization of the stage, which has X- and Y
      direction motion ranges of 300 MUm and a thetaz-direction motion range of +/-3.9
      mrad. The stage measures 150 * 150 * 23 mm, and its aperture is 50 * 50 mm.

PMID- 27036847
TI  - Publisher's Note: "An FPGA-based instrumentation platform for use at deep
      cryogenic temperatures" [Rev. Sci. Instrum. 87, 014701 (2016)].

PMID- 27036848
TI  - Publisher's Note: "A self-adjustable four-point probing system using polymeric
      three dimensional coils and non-toxic liquid metal" [Rev. Sci. Instrum. 86,
      125006 (2015)].

PMID- 27036849
TI  - Clinical implications of oxidative stress and potential role of natural
      antioxidants in diabetic vascular complications.
AB  - AIMS: The possible link between hyperglycaemia-induced oxidative stress (OxS) and
      diabetic complications is suggested by many in vitro studies. However, not much
      attention has been paid to the clinical evidence supporting this hypothesis, as
      well as to their possible therapeutic implications. DATA SYNTHESIS: Some
      prospective studies show a direct correlation between an increase in OxS
      biomarkers and the appearance of diabetes complications. This is consistent with
      the evidence that any acute increase of glycaemia, particularly post-prandial,
      and hypoglycaemia causes endothelial dysfunction and inflammation, through the
      generation of an OxS. However, the detection of free radicals is difficult as
      they are highly reactive molecules with a short half-life. Instead, the
      metabolites of OxS are measured. Interventional trials with supplemented
      antioxidants have failed to show any beneficial effects. Conversely, natural
      foods show very promising results. CONCLUSIONS: The "new antioxidant" approach
      includes the possibility of controlling free radical production and increasing
      intracellular antioxidant defence, a concept different from the old one, when
      antioxidant activities implied scavenging the free radicals already produced. A
      synergistic action in this respect could convincingly be obtained with a balanced
      'Mediterranean Diet' (MedD) type. Early intensive glucose control is still the
      best strategy to avoid OxS and its associated diabetes complications.

PMID- 27036850
TI  - White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset
      Depression and Healthy Controls.
AB  - BACKGROUND: Cerebral white matter lesions (WMLs) are more common in individuals
      with late-onset or late-life depression. It has been proposed that carotid
      atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This
      hemodynamic effect of carotid atherosclerosis could be important for the
      formation of WMLs in depression. METHODS: The case-control study included 29
      patients with late-onset major depressive disorder and 27 controls matched for
      sex, age, and tobacco use. WML volume, carotid intima-media thickness, and
      coronary plaque volume were assessed using magnetic resonance imaging, ultrasound
      scan, and coronary computed tomography (CT) angiography, respectively. RESULTS:
      The mean age for the total sample was 59.7 +/- 4.7 years. There was no difference
      in carotid intima-media thickness between patients and controls (p = 0.164),
      whereas a higher WML volume in the patients was found (p = 0.051). In both
      patients and controls, WML volume was associated with carotid but not with
      coronary atherosclerosis. In adjusted multiple linear regression, a 0.1mm
      increase in averaged carotid intima-media thickness was associated with a 52%
      (95% CI: 8.4-112, p = 0.032) increase in WML volume. The association between
      carotid intima-media thickness and WML volume was, however, similar in patients
      and controls. CONCLUSIONS: In older persons aged between 50 and 70 years, WMLs do
      not seem to be a part of generalized atherosclerotic disease, but seem to be
      dependent on atherosclerosis in the carotid arteries. Carotid atherosclerosis,
      however, could not explain the higher WML load observed in the depressed
      patients, and thus, studies are needed to establish the mechanisms linking
      depression and WMLs.

PMID- 27036852
TI  - SAD phasing: History, current impact and future opportunities.
AB  - Single wavelength anomalous diffraction (SAD) can trace its beginnings to the
      early 1950s. Researchers at the time recognized that SAD offers some unique
      features that might be advantageous for crystallographic phasing, despite the
      fact that at that time recording accurate SAD data was problematic. In this
      review we will follow the trail from those early days, highlighting key advances
      in the field and interpreting them in terms on how they stimulated continued
      phasing development that produced the theoretical foundation for the routine
      macromolecular structure determination by SAD today. The technological advances
      over the past three decades in both hardware and software, which played a
      significant role in making SAD phasing a 'first choice method', will also be
      described. 

PMID- 27036851
TI  - Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase
      Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin
      I phosphorylation.
AB  - We investigated the effect of 7 Hypertrophic Cardiomyopathy (HCM)-causing
      mutations in troponin T (TnT) on troponin function in thin filaments
      reconstituted with actin and human cardiac tropomyosin. We used the quantitative
      in vitro motility assay to study Ca(2+)-regulation of unloaded movement and its
      modulation by troponin I phosphorylation. Troponin from a patient with the K280N
      TnT mutation showed no difference in Ca(2+)-sensitivity when compared with donor
      heart troponin and the Ca(2+)-sensitivity was also independent of the troponin I
      phosphorylation level (uncoupled). The recombinant K280N TnT mutation increased
      Ca(2+)-sensitivity 1.7-fold and was also uncoupled. The R92Q TnT mutation in
      troponin from transgenic mouse increased Ca(2+)-sensitivity and was also
      completely uncoupled. Five TnT mutations (Delta14, Delta28 + 7, DeltaE160, S179F
      and K273E) studied in recombinant troponin increased Ca(2+)-sensitivity and were
      all fully uncoupled. Thus, for HCM-causing mutations in TnT, Ca(2+)-sensitisation
      together with uncoupling in vitro is the usual response and both factors may
      contribute to the HCM phenotype. We also found that Epigallocatechin-3-gallate
      (EGCG) can restore coupling to all uncoupled HCM-causing TnT mutations. In fact
      the combination of Ca(2+)-desensitisation and re-coupling due to EGCG completely
      reverses both the abnormalities found in troponin with a TnT HCM mutation
      suggesting it may have therapeutic potential.

PMID- 27036853
TI  - Incorporation of phosphate into glycogen by glycogen synthase.
AB  - The storage polymer glycogen normally contains small amounts of covalently
      attached phosphate as phosphomonoesters at C2, C3 and C6 atoms of glucose
      residues. In the absence of the laforin phosphatase, as in the rare childhood
      epilepsy Lafora disease, the phosphorylation level is elevated and is associated
      with abnormal glycogen structure that contributes to the pathology. Laforin
      therefore likely functions in vivo as a glycogen phosphatase. The mechanism of
      glycogen phosphorylation is less well-understood. We have reported that glycogen
      synthase incorporates phosphate into glycogen via a rare side reaction in which
      glucose-phosphate rather than glucose is transferred to a growing polyglucose
      chain (Tagliabracci et al. (2011) Cell Metab13, 274-282). We proposed a mechanism
      to account for phosphorylation at C2 and possibly at C3. Our results have since
      been challenged (Nitschke et al. (2013) Cell Metab17, 756-767). Here we extend
      the evidence supporting our conclusion, validating the assay used for the
      detection of glycogen phosphorylation, measurement of the transfer of (32)P from
      [beta-(32)P]UDP-glucose to glycogen by glycogen synthase. The (32)P associated
      with the glycogen fraction was stable to ethanol precipitation, SDS-PAGE and gel
      filtration on Sephadex G50. The (32)P-signal was not affected by inclusion of
      excess unlabeled UDP before analysis or by treatment with a UDPase, arguing
      against the signal being due to contaminating [beta-(32)P]UDP generated in the
      reaction. Furthermore, [(32)P]UDP did not bind non-covalently to glycogen. The
      (32)P associated with glycogen was released by laforin treatment, suggesting that
      it was present as a phosphomonoester. The conclusion is that glycogen synthase
      can mediate the introduction of phosphate into glycogen, thereby providing a
      possible mechanism for C2, and perhaps C3, phosphorylation.

PMID- 27036854
TI  - Low temperature plasma processing for cell growth inspired carbon thin films
      fabrication.
AB  - The recent bio-applications (i.e. bio-sensing, tissue engineering and cell
      proliferation etc.) are driving the fundamental research in carbon based
      materials with functional perspectives. High stability in carbon based coatings
      usually demands the high density deposition. However, the standard techniques,
      used for the large area and high throughput deposition of crystalline carbon
      films, often require very high temperature processing (typically >800  degrees C
      in inert atmosphere). Here, we present a low temperature (<150  degrees C) pulsed
      DC plasma sputtering process, which enables sufficient ion flux to deposit dense
      unhydrogenated carbon thin films without any need of substrate-bias or post
      deposition thermal treatments. It is found that the control over plasma power
      density and pulsed frequency governs the density and kinetic energy of carbon
      ions participating during the film growth. Subsequently, it controls the contents
      of sp(3) and sp(2) hybridizations via conversion of sp(2) to sp(3) hybridization
      by ion's energy relaxation. The role of plasma parameters on the chemical and
      surface properties are presented and correlated to the bio-activity. Bioactivity
      tests, carried out in mouse fibroblast L-929 and Sarcoma osteogenic (Saos-2) bone
      cell lines, demonstrate promising cell-proliferation in these films.

PMID- 27036856
TI  - A multiplexed targeted assay for high-throughput quantitative analysis of serum
      methylamines by ultra performance liquid chromatography coupled to high
      resolution mass spectrometry.
AB  - Methylamines are biologically-active metabolites present in serum and urine
      samples, which play complex roles in metabolic diseases. Methylamines can be
      detected by proton nuclear magnetic resonance (NMR), but specific methods remain
      to be developed for their routine assay in human serum in clinical settings. Here
      we developed and validated a novel reliable "methylamine panel" method for
      simultaneous quantitative analysis of trimethylamine (TMA), its major
      detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline,
      betaine and l-carnitine in human serum using Ultra Performance Liquid
      Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS).
      Metabolite separation was carried out on a HILIC stationary phase. For all
      metabolites, the assay was linear in the range of 0.25-12.5 MUmol/L and enabled
      to reach limit of detection of about 0.10 MUmol/L. Relative standard deviations
      were below 16% for the three levels of concentrations. We demonstrated the strong
      reliability and robustness of the method, which was applied to serum samples from
      healthy individuals to establish the range of concentrations of the metabolites
      and their correlation relationships and detect gender differences. Our data
      provide original information for implementing in a clinical environment a MS
      based diagnostic method with potential for targeted metabolic screening of
      patients at risk of cardiometabolic diseases.

PMID- 27036855
TI  - Cyp1b1 affects external control of mouse hepatocytes, fatty acid homeostasis and
      signaling involving HNF4alpha and PPARalpha.
AB  - Cytochrome P450 1b1 (Cyp1b1) is expressed in endothelia, stellate cells and pre
      adipocytes, but not hepatocytes. Deletion alters liver fatty acid metabolism and
      prevents obesity and hepatic steatosis. This suggests a novel extra-hepatocyte
      regulation directed from cells that express Cyp1b1. To characterize these
      mechanisms, microarray gene expression was analyzed in livers of normal and
      congenic Cyp1b1-ko C57BL/6 J mice fed either low or high fat diets. Cyp1b1-ko
      gene responses indicate suppression of endogenous PPARalpha activity, a switch
      from triglyceride storage to mitochondrial fatty acid oxidation and decreased
      oxidative stress. Many gene responses in Cyp1b1-ko are sexually dimorphic and
      correspond to increased activity of growth hormone mediated by HNF4alpha. Male
      responses stimulated by GH pulses are enhanced, whereas responses that decline
      exhibit further suppression, including Cyp regulation by PPARalpha, CAR and PXR.
      These effects of Cyp1b1 deletion overlap with effects caused by deletion of the
      small heterodimeric partner, a suppressor of these nuclear factors. Redirection
      of gene expression associated with liver fat homeostasis in Cyp1b1-ko mice that
      directs hypothalamic control of GH and leptin. Cyp1b1-ko suppresses neonatal Scd1
      and delays adult maturation of dimorphic GH/HNF4alpha signaling. Alternatively,
      deletion may diminish hypothalamic metabolism of estradiol, which establishes
      adult GH regulation.

PMID- 27036857
TI  - Obesity is associated with more disability at presentation and after treatment in
      low back pain but not in neck pain: findings from the OIOC registry.
AB  - BACKGROUND: The influence on the treatment response in patients with low back
      pain (LBP) and neck pain (NP) is unknown. The aim of the study was to investigate
      the influence of body weight in patients with low back pain (LBP) and neck pain
      (NP) on baseline and end of treatment disability. METHODS: Cross-sectional
      analysis of baseline factors. Longitudinal analysis of prospectively collected
      patient information at an outpatient physical therapy registry (data from June
      2010 to December 2012). WHO-BMI classification was used: underweight, lean,
      overweight, obesity class I, obesity class II and III. The influence of body
      weight and a predefined set of confounders was analyzed by multiple regression
      models. RESULTS: In LBP, disability increased with increasing BMI [lean =
      reference, obesity class I Beta 5.41 (95 % CI 0.75; 10.07), obesity class II-III
      Beta 7.58 (95 % CI 2.13; 13.03)]. Compared to lean patients, disability after
      treatment improved in overweight subjects [Beta -3.90 (95 % CI -7.4; -0.41)] but
      not in subjects with obesity class II-III [Beta 3.43 (95 % CI -3.81; 10.68)].
      There were insufficient patients in the sample with severe obesity and therefore
      this trend has to be confirmed. The likelihood for meaningful important change
      (MID) was similar in all BMI subgroups. For patients with NP, BMI was not
      associated with baseline disability, and did not predict end of treatment
      disability or the likelihood of a MID. These findings must be interpreted with
      caution as BMI subgroups did not meet the required sample size. CONCLUSION:
      Overweight and obesity are associated with higher levels of disability before
      treatment in LBP patients, but not in NP. In severely obese patients class II-III
      with LBP the rate of MID was lowest indicating that these patients experienced
      the least treatment response compared to the other groups. Further studies should
      address the impact of severe obesity on the prognosis of LBP. In patients with
      LBP, severe obesity may be an important factor to consider during the physical
      therapy treatment. In particular, combined treatment strategies combining weight
      management, cardiovascular fitness, and low back pain rehabilitation should be
      investigated.

PMID- 27036858
TI  - Robot-assisted Laparoscopic Extravesical Ureteral Reimplantation: Technique
      Modifications Contribute to Optimized Outcomes.
AB  - BACKGROUND: Robot-assisted laparoscopic extravesical ureteral reimplantation
      (RALUR-EV) is being adopted at large pediatric urology centers in the United
      States, but currently there is not consensus on surgical technique to facilitate
      the best possible outcomes. OBJECTIVE: To describe technique modifications that
      may lead to improved radiographic vesicoureteral reflux (VUR) resolution. DESIGN,
      SETTING, AND PARTICIPANTS: Between December 2008 and February 2015, a single
      surgeon performed RALUR-EV at an academic medical center. Only children with
      persistent grade 3-5 VUR at age 5 yr on voiding cystourethrogram (VCUG), those
      who had breakthrough urinary tract infections, or those with renal scarring were
      selected to undergo surgical correction of VUR with RALUR-EV. Children undergoing
      RALUR-EV for obstructive megaureter or ureterovesical junction obstruction were
      excluded. Fifty-eight patients (83 ureters) fit the inclusion criteria. SURGICAL
      PROCEDURE: We highlighted adjustments to our technique, called LUAA to represent
      length of detrusor tunnel (L), use of a U stitch (U), placement of permanent
      ureteral alignment suture (A), and inclusion of ureteral adventitia (A) in
      detrusorraphy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end
      point was resolution of VUR on postoperative VCUG. RESULTS AND LIMITATIONS:
      Because technique modifications were made at two distinct time points, we
      generated three patient groups for comparison. We observed complete resolution of
      VUR in 82% of ureters, including 8 of 12 ureters (67%), 8 of 11 ureters (73%),
      and 52 of 60 ureters (87%) for technique modification cohorts 1, 2, and 3,
      respectively. There were no ureteral complications at median follow-up of 30 mo.
      Retrospective design and possible confounding from the learning curve limit this
      study. CONCLUSIONS: Using the standardized LUAA technique, we demonstrated an
      improvement in outcomes. Given the wide range of published resolution rates
      following RALUR-EV, there is a need for standardization of technique to
      facilitate best possible outcomes. We propose the LUAA technique as a new
      standard for RALUR-EV to achieve this goal. PATIENT SUMMARY: We examined the
      safety and efficacy of a minimally invasive surgery in children. We identified
      several critical adjustments to surgical technique that improve rates of
      successful outcome.

PMID- 27036859
TI  - Journal of Pediatric Surgery 1966-2016: Fifty years and moving forward.

PMID- 27036860
TI  - SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis.
AB  - To establish the cause of primary aldosteronism (PA), it is essential to
      distinguish unilateral from bilateral adrenal aldosterone secretion, as
      adrenalectomy improves aldosterone secretion and controls hypertension and
      hypokalemia only in the former. Except in the rare cases of type 1 or 3 familial
      hyperaldosteronism, which can be diagnosed genetically and are not candidates for
      surgery, lateralized aldosterone secretion is diagnosed on adrenal CT or MRI and
      adrenal venous sampling. Postural stimulation tests and (131)I-norcholesterol
      scintigraphy have poor diagnostic value and (11)C-metomidate PET is not yet
      available. We recommend that adrenal CT or MRI be performed in all cases of PA.
      Imaging may exceptionally identify adrenocortical carcinoma, for which the
      surgical objectives are carcinologic, and otherwise shows either normal or
      hyperplastic adrenals or unilateral adenoma. Imaging alone carries a risk of
      false positives in patients over 35 years of age (non-aldosterone-secreting
      adenoma) and false negatives in all patients (unilateral hyperplasia). We suggest
      that all candidates for surgery over 35 years of age undergo adrenal venous
      sampling, simultaneously in both adrenal veins, without ACTH stimulation, to
      confirm the unilateral form of the hypersecretion. Sampling results should be
      confirmed on adrenal vein cortisol assay showing a concentration at least double
      that found in peripheral veins. Aldosterone secretion should be considered
      lateralized when aldosterone/cortisol ratio on the dominant side is at least 4
      fold higher than contralaterally. 

PMID- 27036861
TI  - Folding complex DNA nanostructures from limited sets of reusable sequences.
AB  - Scalable production of DNA nanostructures remains a substantial obstacle to
      realizing new applications of DNA nanotechnology. Typical DNA nanostructures
      comprise hundreds of DNA oligonucleotide strands, where each unique strand
      requires a separate synthesis step. New design methods that reduce the strand
      count for a given shape while maintaining overall size and complexity would be
      highly beneficial for efficiently producing DNA nanostructures. Here, we report a
      method for folding a custom template strand by binding individual staple
      sequences to multiple locations on the template. We built several nanostructures
      for well-controlled testing of various design rules, and demonstrate folding of a
      6-kb template by as few as 10 unique strand sequences binding to 10 +/- 2
      locations on the template strand.

PMID- 27036862
TI  - The histone chaperone Vps75 forms multiple oligomeric assemblies capable of
      mediating exchange between histone H3-H4 tetramers and Asf1-H3-H4 complexes.
AB  - Vps75 is a histone chaperone that has been historically characterized as
      homodimer by X-ray crystallography. In this study, we present a crystal structure
      containing two related tetrameric forms of Vps75 within the crystal lattice. We
      show Vps75 associates with histones in multiple oligomers. In the presence of
      equimolar H3-H4 and Vps75, the major species is a reconfigured Vps75 tetramer
      bound to a histone H3-H4 tetramer. However, in the presence of excess histones, a
      Vps75 dimer bound to a histone H3-H4 tetramer predominates. We show the Vps75-H3
      H4 interaction is compatible with the histone chaperone Asf1 and deduce a
      structural model of the Vps75-Asf1-H3-H4 (VAH) co-chaperone complex using the
      Pulsed Electron-electron Double Resonance (PELDOR) technique and cross-linking
      MS/MS distance restraints. The model provides a molecular basis for the
      involvement of both Vps75 and Asf1 in Rtt109 catalysed histone H3 K9 acetylation.
      In the absence of Asf1 this model can be used to generate a complex consisting of
      a reconfigured Vps75 tetramer bound to a H3-H4 tetramer. This provides a
      structural explanation for many of the complexes detected biochemically and
      illustrates the ability of Vps75 to interact with dimeric or tetrameric H3-H4
      using the same interaction surface.

PMID- 27036863
TI  - CRISPR-mediated control of the bacterial initiation of replication.
AB  - Programmable control of the cell cycle has been shown to be a powerful tool in
      cell-biology studies. Here, we develop a novel system for controlling the
      bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of
      replication locus. Initiation of replication of bacterial chromosomes is
      accurately regulated by the DnaA protein, which promotes the unwinding of DNA at
      oriC We demonstrate that the binding of CRISPR/dCas9 to any position within
      origin or replication blocks the initiation of replication. Serial-dilution
      plating, single-cell fluorescence microscopy, and flow-cytometry experiments show
      that ongoing rounds of chromosome replication are finished upon CRISPR/dCas9
      binding, but no new rounds are initiated. Upon arrest, cells stay metabolically
      active and accumulate cell mass. We find that elevating the temperature from 37
      to 42 degrees C releases the CRISR/dCas9 replication inhibition, and we use this
      feature to recover cells from the arrest. Our simple and robust method of
      controlling the bacterial cell cycle is a useful asset for synthetic biology and
      DNA-replication studies in particular. The inactivation of CRISPR/dCas9 binding
      at elevated temperatures may furthermore be of wide interest for CRISPR/Cas9
      applications in genomic engineering.

PMID- 27036864
TI  - Quantifying the ion atmosphere of unfolded, single-stranded nucleic acids using
      equilibrium dialysis and single-molecule methods.
AB  - To form secondary structure, nucleic acids (NAs) must overcome electrostatic
      strand-strand repulsion, which is moderated by the surrounding atmosphere of
      screening ions. The free energy of NA folding therefore depends on the
      interactions of this ion atmosphere with both the folded and unfolded states. We
      quantify such interactions using the preferential ion interaction coefficient or
      ion excess: the number of ions present near the NA in excess of the bulk
      concentration. The ion excess of the folded, double-helical state has been
      extensively studied; however, much less is known about the salt-dependent ion
      excess of the unfolded, single-stranded state. We measure this quantity using
      three complementary approaches: a direct approach of Donnan equilibrium dialysis
      read out by atomic emission spectroscopy and two indirect approaches involving
      either single-molecule force spectroscopy or existing thermal denaturation data.
      The results of these three approaches, each involving an independent experimental
      technique, are in good agreement. Even though the single-stranded NAs are
      flexible polymers that are expected to adopt random-coil configurations, we find
      that their ion atmosphere is quantitatively described by rod-like models that
      neglect large-scale conformational freedom, an effect that we explain in terms of
      the competition between the relevant structural and electrostatic length scales.

PMID- 27036865
TI  - Cardiovascular efficacy of sitagliptin in patients with diabetes at high risk of
      cardiovascular disease: a 12-month follow-up.
AB  - BACKGROUND: Gliptins should have beneficial effects beyond glycemic control,
      potentially on the pathophysiology of cardiovascular (CV) diseases, with some
      basic studies demonstrating this possibility. However, we are yet to answer
      whether there are any direct CV effects in the clinical setting. We aimed to
      examine the beneficial effects of sitagliptin in Japanese patients with diabetes
      and high CV risk for 12 months. METHODS: This was a prospective, multicenter,
      observational study of 205 patients with type 2 diabetes. All participants had
      more than one major CV risk factor and were treated with sitagliptin for 12
      months. At 3 or 12 months, we examined the effects of treatment on glycemic
      control, CV function (by electrocardiography, echocardiography, and reactive
      hyperemia-peripheral arterial tonometry), and CV biomarkers. RESULTS: Patients
      were predominantly elderly (68.8 +/- 9.9 years) and male (71.5 %) and typically
      had more than three CV risk factors (79.2 %). Treatment with sitagliptin
      significantly reduced the hemoglobin A1c (HbA1c) level from 7.09 % +/- 0.81 % at
      baseline to 6.67 % +/- 0.69 % at 3 months and 6.68 % +/- 0.73 % at 12 months
      (both P < 0.001). The reduction in HbA1c was also in tandem with the decrease in
      the level of high-sensitive C-reactive protein throughout the study. Independent
      of the change in HbA1c, sitagliptin reduced systolic (-7.0 +/- 18.9 mmHg) and
      diastolic blood pressure (-5.1 +/- 11.7 mmHg) at 12 months, and this was
      associated with a decrease in urinary albumin. In contrast, there were no
      beneficial effects on cardiac and endothelial function or on the levels of serum
      B-type natriuretic peptide, high-sensitive troponin T, and urinary 8-hydroxy-2'
      deoxyguanosine. CONCLUSIONS: In Japanese patients with diabetes and multiple CV
      risk factors, sitagliptin showed a decrease in blood pressure associated with an
      improvement in albuminuria in addition to glycemic control. TRIAL REGISTRATION:
      UMIN000005663.

PMID- 27036866
TI  - Withdrawal of Heart Failure Medications in Cancer Survivors With Chemotherapy
      Induced Left Ventricular Dysfunction: A Pilot Study.

PMID- 27036867
TI  - Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.
AB  - The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe
      pulmonary arterial hypertension. While it is known that exposure to hypoxia can
      be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown
      whether abnormal pulmonary blood flow (PBF), which has long been known to invoke
      pathological changes in the pulmonary vasculature, can replace the hypoxic
      exposure. Here we studied if a combination of SU5416 administration combined with
      pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is
      sufficient to induce severe pulmonary arterial hypertension (PAH) in rats.
      Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left
      pneumonectomy) or standard SuHx protocol, and comparisons between models were
      made at week 2 and 6 postinitiation. Both SuHx and SuPNx models displayed
      extensive obliterative vascular remodeling leading to an increased right
      ventricular systolic pressure at week 6 Similar inflammatory response in the lung
      vasculature of both models was observed alongside increased endothelial cell
      proliferation and apoptosis. This study describes the SuPNx model, which features
      severe PAH at 6 wk and could serve as an alternative to the SuHx model. Our
      study, together with previous studies on experimental models of pulmonary
      hypertension, shows that the typical histopathological findings of PAH, including
      obliterative lesions, inflammation, increased cell turnover, and ongoing
      apoptosis, represent a final common pathway of a disease that can evolve as a
      consequence of a variety of insults to the lung vasculature.

PMID- 27036868
TI  - Hsp90 inhibition suppresses NF-kappaB transcriptional activation via Sirt-2 in
      human lung microvascular endothelial cells.
AB  - The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-kappaB
      mediated transcription is the major basis for their anti-inflammatory properties.
      While the molecular mechanisms underlying this effect are not clear, they appear
      to be distinct in human endothelial cells. We now show for the first time that
      type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-kappaB target gene
      promoter and prevents the recruitment of NF-kappaB proteins and subsequent
      assembly of RNA polymerase II complex in human lung microvascular endothelial
      cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a
      "transcriptional block," which is reversed by either inhibition or downregulation
      of Sirt-2 protein expression. Furthermore, this process is independent of NF
      kappaB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known
      Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-kappaB
      target gene promoter via interaction with core histones. Upon inflammatory
      challenge, chromatin remodeling and core histone H3 displacement from the
      promoter region removes Sirt-2 and allows NF-kappaB/coactivator recruitment
      essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have
      important implications in pulmonary inflammation.

PMID- 27036869
TI  - Noncanonical WNT-5B signaling induces inflammatory responses in human lung
      fibroblasts.
AB  - COPD is a progressive chronic lung disease characterized by pulmonary
      inflammation. Several recent studies indicate aberrant expression of WNT ligands
      and Frizzled receptors in the disease. For example, WNT-5A/B ligand expression
      was recently found to be increased in lung fibroblasts of COPD patients. However,
      possible effects of WNT-5A and WNT-5B on inflammation have not been investigated
      yet. In this study, we assessed the regulation of inflammatory cytokine release
      in response to WNT-5A/B signaling in human lung fibroblasts. Primary human fetal
      lung fibroblasts (MRC-5), and primary lung fibroblasts from COPD patients and non
      COPD controls were treated with recombinant WNT-5A or WNT-5B to assess IL-6 and
      CXCL8 cytokine secretion and gene expression levels. Following WNT-5B, and to a
      lesser extent WNT-5A stimulation, fibroblasts showed increased IL-6 and CXCL8
      cytokine secretion and mRNA expression. WNT-5B-mediated IL-6 and CXCL8 release
      was higher in fibroblasts from COPD patients than in non-COPD controls. In MRC-5
      fibroblasts, WNT-5B-induced CXCL8 release was mediated primarily via the Frizzled
      2 receptor and TAK1 signaling, whereas canonical beta-catenin signaling was not
      involved. In further support of noncanonical signaling, we showed activation of
      JNK, p38, and p65 NF-kappaB by WNT-5B. Furthermore, inhibition of JNK and p38
      prevented WNT-5B-induced IL-6 and CXCL8 secretion, whereas IKK inhibition
      prevented CXCL8 secretion only, indicating distinct pathways for WNT-5B-induced
      IL-6 and CXCL8 release. WNT-5B induces IL-6 and CXCL8 secretion in pulmonary
      fibroblasts. In summary, WNT-5B mediates this via Frizzled-2 and TAK1. As WNT-5
      signaling is increased in COPD, this WNT-5-induced inflammatory response could
      represent a therapeutic target.

PMID- 27036870
TI  - 27-Hydroxycholesterol accelerates cellular senescence in human lung resident
      cells.
AB  - Cellular senescence is reportedly involved in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). We previously showed that 27
      hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared
      with those in healthy subjects. The aim of this study was to investigate whether
      lung fibroblasts of COPD patients are senescent and to determine the effects of
      27-OHC on senescence of lung resident cells, including fibroblasts and airway
      epithelial cells. Localization of senescence-associated proteins and sterol 27
      hydroxylase was investigated in the lungs of COPD patients by immunohistochemical
      staining. To evaluate whether 27-OHC accelerates cellular senescence, lung
      resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated
      tissue repair were investigated in the 27-OHC-treated cells. Expression of
      senescence-associated proteins was significantly enhanced in lung fibroblasts of
      COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly
      upregulated in lung fibroblasts and alveolar macrophages in these patients.
      Treatment with the concentration of 27-OHC detected in COPD airways significantly
      augmented expression of senescence-associated proteins and senescence-associated
      beta-galactosidase activity, and delayed cell growth through the prostaglandin E2
      reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue
      repair function. Fibroblasts from lungs of COPD patients showed accelerated
      senescence and were more susceptible to 27-OHC-induced cellular senescence
      compared with those of healthy subjects. In conclusion, 27-OHC accelerates
      cellular senescence in lung resident cells and may play a pivotal role in
      cellular senescence in COPD.

PMID- 27036871
TI  - Autophagy plays an essential role in cigarette smoke-induced expression of MUC5AC
      in airway epithelium.
AB  - Mucus hypersecretion is a common pathological feature of chronic airway
      inflammatory diseases including chronic obstructive pulmonary disease (COPD).
      However, the molecular basis for this condition remains incompletely understood.
      We have previously demonstrated a critical role of autophagy in COPD pathogenesis
      through mediating apoptosis of lung epithelial cells. In this study, we aimed to
      investigate the function of autophagy as well as its upstream and downstream
      signals in cigarette smoke-induced mucus production in human bronchial epithelial
      (HBE) cells and in mouse airways. Cigarette smoke extract (CSE), as well as the
      classical autophagy inducers starvation or Torin-1, significantly triggered
      MUC5AC expression, and inhibition of autophagy markedly attenuated CSE-induced
      mucus production. The CSE-induced autophagy was mediated by mitochondrial
      reactive oxygen species (mitoROS), which regulated mucin expression through the
      JNK and activator protein-1 pathway. Epidermal growth factor receptor (EGFR) was
      also required for CSE-induced MUC5AC in HBE cells, but it exerted inconsiderable
      effects on the autophagy-JNK signaling cascade. Airways of mice with
      dysfunctional autophagy-related genes displayed a markedly reduced number of
      goblet cells and attenuated levels of Muc5ac in response to cigarette smoke
      exposure. These results altogether suggest that mitoROS-dependent autophagy is
      essential for cigarette smoke-induced mucus hyperproduction in airway epithelial
      cells, and reemphasize autophagy inhibition as a novel therapeutic strategy for
      chronic airway diseases.

PMID- 27036872
TI  - Hepatocyte growth factor as a downstream mediator of vascular endothelial growth
      factor-dependent preservation of growth in the developing lung.
AB  - Impaired vascular endothelial growth factor (VEGF) signaling contributes to the
      pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that the
      effects of VEGF on lung structure during development may be mediated through its
      downstream effects on both endothelial nitric oxide synthase (eNOS) and
      hepatocyte growth factor (HGF) activity, and that, in the absence of eNOS,
      trophic effects of VEGF would be mediated through HGF signaling. To test this
      hypothesis, we performed an integrative series of in vitro (fetal rat lung
      explants and isolated fetal alveolar and endothelial cells) and in vivo studies
      with normal rat pups and eNOS(-/-) mice. Compared with controls, fetal lung
      explants from eNOS(-/-) mice had decreased terminal lung bud formation, which was
      restored with recombinant human VEGF (rhVEGF) treatment. Neonatal eNOS(-/-) mice
      were more susceptible to hyperoxia-induced inhibition of lung growth than
      controls, which was prevented with rhVEGF treatment. Fetal alveolar type II (AT2)
      cell proliferation was increased with rhVEGF treatment only with mesenchymal cell
      (MC) coculture, and these effects were attenuated with anti-HGF antibody
      treatment. Unlike VEGF, HGF directly stimulated isolated AT2 cells even without
      MC coculture. HGF directly stimulates fetal pulmonary artery endothelial cell
      growth and tube formation, which is attenuated by treatment with JNJ-38877605, a
      c-Met inhibitor. rHGF treatment preserves alveolar and vascular growth after
      postnatal exposure to SU-5416, a VEGF receptor inhibitor. We conclude that the
      effects of VEGF on AT2 and endothelial cells during lung development are partly
      mediated through HGF-c-Met signaling and speculate that reciprocal VEGF-HGF
      signaling between epithelia and endothelia is disrupted in infants who develop
      BPD.

PMID- 27036873
TI  - Clinical Trial Patient-reported Outcomes Data: Going Beyond the Label in
      Oncology.
AB  - PURPOSE: Patient-reported outcome (PRO) data are increasingly being implemented
      in oncology clinical trial research to evaluate treatment benefit, such as
      disease-related symptoms, treatment-related adverse events, and health-related
      quality of life impacts. However, only a small amount of PRO data collected is
      used to support labeling claims, leaving a substantial amount of data that could
      be shared by sponsors to further convey treatment benefit from the patient
      perspective. METHODS: This paper describes how pharmaceutical sponsors can
      realize the value of PRO data derived from oncology trials with regard to the
      following stakeholders: payers, health care providers (HCPs), and patient
      advocacy groups. Further, ideas are presented for integrating PRO data and
      implementing PRO assessments within oncology, by stakeholder type. Finally, a
      summary is provided to describe how PRO data can benefit the patient by
      facilitating better, more symptom-focused care and enhancing treatment decisions.
      FINDINGS: With the goal of motivating further use of PRO assessments in oncology,
      we present examples of how payers utilize PRO data to inform reimbursement
      decisions (eg, PRO data inform decisions made by Germany's Institute for Quality
      and Efficiency in Health Care and the United Kingdom's National Institute for
      Health and Care Excellence); how communication of results with patient advocacy
      groups can lead to a better understanding of what is important to patients; and
      how HCPs can use PRO instruments to inform patient treatment decisions through
      real-world application. IMPLICATIONS: Integrating PRO data can enhance health
      care by allowing the patient's voice to carry beyond regulatory decisions and
      into those made by payers and HCPs, which are crucial to quality care and
      assessing the value of care. Utilizing PRO assessments and communicating results
      to key stakeholders in the oncology space can allow sponsors to report treatment
      benefit and, more importantly, can provide valuable insight into the patient
      treatment experience.

PMID- 27036874
TI  - Inter-regulation of IGFBP1 and FOXO3a unveils novel mechanism in ursolic acid
      inhibited growth of hepatocellular carcinoma cells.
AB  - BACKGROUND: Ursolic acid (UA), a natural pentacyclic triterpenoid, exerts anti
      tumor effects in various cancer types including hepatocellular carcinoma (HCC).
      However, the molecular mechanisms underlying this remain largely unknown.
      METHODS: Cell viability and cell cycle were examined by MTT and Flow cytometry
      assays. Western blot analysis was performed to measure the phosphorylation and
      protein expression of p38 MAPK, insulin-like growth factor (IGF) binding protein
      1 (IGFBP1) and forkhead box O3A (FOXO3a). Quantitative real-time PCR (qRT-PCR)
      was used to examine the mRNA levels of IGFBP1 gene. Small interfering RNAs
      (siRNAs) method was used to knockdown IGFBP1 gene. Exogenous expressions of
      IGFBP1 and FOXO3a were carried out by transient transfection assays. IGFBP1
      promoter activity was measured by Secrete-PairTM Dual Luminescence Assay Kit . In
      vivo nude mice xenograft model and bioluminescent imaging system were used to
      confirm the findings in vitro. RESULTS: We showed that UA stimulated
      phosphorylation of p38 MAPK. In addition, UA increased the protein, mRNA levels,
      and promoter activity of IGFBP1, which was abrogated by the specific inhibitor of
      p38 MAPK (SB203580). Intriguingly, we showed that UA increased the expression of
      FOXO3a and that overexpressed FOXO3a enhanced phosphorylation of p38 MAPK, all of
      which were not observed in cells silencing of endogenous IGFBP1 gene. Moreover,
      exogenous expressed IGFBP1 strengthened UA-induced phosphorylation of p38 MAPK
      and FOXO3a protein expression, and more importantly, restored the effect of UA
      inhibited growth in cells silencing of endogenous IGFBP1 gene. Consistent with
      these, UA suppressed tumor growth and increased phosphorylation of p38 MAPK,
      protein expressions of IGFBP1 and FOXO3a in vivo. CONCLUSION: Collectively, our
      results show that UA inhibits growth of HCC cells through p38 MAPK-mediated
      induction of IGFBP1 and FOXO3a expression. The interactions between IGFBP1 and
      FOXO3a, and feedback regulatory loop of p38 MAPK by IGFBP1 and FOXO3a resulting
      in reciprocal pathways, contribute to the overall effects of UA. This in vitro
      and in vivo study corroborates a potential novel mechanism by which UA controls
      HCC growth and implies that the rational targeting IGFBP1 and FOXO3a can be
      potential for the therapeutic strategy against HCC.

PMID- 27036875
TI  - Modulating prefrontal control in humans reveals distinct pathways to competitive
      success and collective waste.
AB  - Competitive decision making may require controlling and calculative mind-sets. We
      examined this possibility in repeated predator-prey contests by up- or down
      regulating the individual's right inferior frontal gyrus (rIFG), a brain region
      involved in impulse inhibition and mentalizing. Following brain stimulation,
      subjects invested as predator or prey against a non-treated antagonist. Relative
      to sham-treatment (i) prey-defense was relatively frequent, strong and unaffected
      by stimulation, (ii) down-regulating predator rIFG produced a high-firing
      strategy-predators earned more because they attacked more frequently, while (iii)
      up-regulating predator rIFG produced a track-and-attack strategy-predators earned
      more because they attacked especially when their (non-stimulated) antagonist
      lowered its prey-defense. Results suggest that calculative mindsets are not
      needed to compete effectively, especially not when the goal is to survive.
      Enhanced prefrontal control enables individuals to appear less aggressive without
      sacrificing competitive effectiveness-it provides human predators with an iron
      fist in a velvet glove.

PMID- 27036877
TI  - Telemedicine vs. in-person delivery of intensive short-term dynamic psychotherapy
      for patients with medically unexplained pain: A 12-month randomized, controlled
      trial.
AB  - Introduction This study examined the effectiveness of telemedicine in providing
      psychotherapy to patients with medically unexplained pain (MUP) who may not have
      access to in-person treatment. The impact of Internet-delivered intensive short
      term dynamic psychotherapy (ID-ISTDP) was investigated for MUP via video
      teleconferencing (SkypeTM). Methods A randomized, controlled trial of ISTDP, an
      evidence-based intervention for MUP, was conducted to compare delivery modalities
      on variations in MUP symptoms. Eighty-one participants with MUP were randomized
      to either ID-ISTDP ( n = 39) or in-person ISTDP ( n = 42). Outcome variables
      included the Numeric Pain Rating Scale, Depression Anxiety Stress Scale-21,
      Emotion Regulation Questionnaire, Mindful Attention Awareness Scale and the
      Quality of Life Inventory. In addition, exploratory analyses were used to examine
      acceptability, satisfaction and compliance in both conditions. Participants were
      assessed prior to intervention, immediately following the intervention, and 12
      months after. Results In the intention-to-treat analysis, in-person ISTDP
      participants had significantly lower pain intensity than ID-ISTDP participants,
      both immediately following the intervention ( d = 0.97) and at the 12-month
      follow-up ( d = 0.82). Moreover, there were significant decreases in depression,
      anxiety and stress as well as a greater increase in emotion regulation
      functioning, mindfulness and quality of life observed in the in-person ISTDP
      group at the end of the intervention and 12 months after the treatment when
      compared to the ID-ISTDP group. Participants rated both treatment conditions as
      equally credible and satisfying. Conclusion ISTDP seems most effective when
      delivered in person in treating MUP patients with highly comorbid conditions with
      benefits maintained over 12 months.

PMID- 27036876
TI  - An oxytocin receptor polymorphism predicts amygdala reactivity and antisocial
      behavior in men.
AB  - Variability in oxytocin (OXT) signaling is associated with individual differences
      in sex-specific social behavior across species. The effects of OXT signaling on
      social behavior are, in part, mediated through its modulation of amygdala
      function. Here, we use imaging genetics to examine sex-specific effects of three
      single-nucleotide polymorphisms in the human oxytocin receptor gene (OXTR;
      rs1042778, rs53576 and rs2254298) on threat-related amygdala reactivity and
      social behavior in 406 Caucasians. Analyses revealed that among men but not
      women, OXTR rs1042778 TT genotype was associated with increased right amygdala
      reactivity to angry facial expressions, which was uniquely related to higher
      levels of antisocial behavior among men. Moderated meditation analysis suggested
      a trending indirect effect of OXTR rs1042778 TT genotype on higher antisocial
      behavior via increased right amygdala reactivity to angry facial expressions in
      men. Our results provide evidence linking genetic variation in OXT signaling to
      individual differences in amygdala function. The results further suggest that
      these pathways may be uniquely important in shaping antisocial behavior in men.

PMID- 27036878
TI  - Developing a measure of engagement with telehealth systems: The mHealth
      Technology Engagement Index.
AB  - Introduction Telehealth systems and mobile health (mHealth) devices allow for the
      exchange of both physical and mental healthcare data, as well as information from
      a patient to a practitioner, or care recipient to caregiver; but there has been
      little research on why users are motivated to engage with telehealth systems.
      Given this, we sought to create a measure that satisfactorily assesses human
      motivation to use telehealth devices. Methods 532 survey responses were used in
      an exploratory factor analysis and confirmatory factor analysis, which tested and
      retested the feasibility of this new measure. Convergent and divergent validity
      analyses indicated that the mHealth Technology Engagement Index (mTEI) is a
      unique measure of motivation. Results The results indicated that autonomy,
      competence, relatedness, goal attainment, and goal setting underpin motivation to
      use telehealth systems. Discussion The mTEI shows promise in indexing human
      motivation to use telehealth technologies. We also discuss the importance of
      developing measurement tools based on theory and how practitioners can best
      utilize the mTEI.

PMID- 27036879
TI  - Validity and reliability of Internet-based physiotherapy assessment for
      musculoskeletal disorders: a systematic review.
AB  - Purpose The purpose of this review is to systematically explore and summarise the
      validity and reliability of telerehabilitation (TR)-based physiotherapy
      assessment for musculoskeletal disorders. Method A comprehensive systematic
      literature review was conducted using a number of electronic databases: PubMed,
      EMBASE, PsycINFO, Cochrane Library and CINAHL, published between January 2000 and
      May 2015. The studies examined the validity, inter- and intra-rater reliabilities
      of TR-based physiotherapy assessment for musculoskeletal conditions were
      included. Two independent reviewers used the Quality Appraisal Tool for studies
      of diagnostic Reliability (QAREL) and the Quality Assessment of Diagnostic
      Accuracy Studies (QUADAS) tool to assess the methodological quality of
      reliability and validity studies respectively. Results A total of 898 hits were
      achieved, of which 11 articles based on inclusion criteria were reviewed. Nine
      studies explored the concurrent validity, inter- and intra-rater reliabilities,
      while two studies examined only the concurrent validity. Reviewed studies were
      moderate to good in methodological quality. The physiotherapy assessments such as
      pain, swelling, range of motion, muscle strength, balance, gait and functional
      assessment demonstrated good concurrent validity. However, the reported
      concurrent validity of lumbar spine posture, special orthopaedic tests,
      neurodynamic tests and scar assessments ranged from low to moderate. Conclusion
      TR-based physiotherapy assessment was technically feasible with overall good
      concurrent validity and excellent reliability, except for lumbar spine posture,
      orthopaedic special tests, neurodynamic testa and scar assessment.

PMID- 27036880
TI  - Systematic identification of genetic influences on methylation across the human
      life course.
AB  - BACKGROUND: The influence of genetic variation on complex diseases is potentially
      mediated through a range of highly dynamic epigenetic processes exhibiting
      temporal variation during development and later life. Here we present a catalogue
      of the genetic influences on DNA methylation (methylation quantitative trait loci
      (mQTL)) at five different life stages in human blood: children at birth,
      childhood, adolescence and their mothers during pregnancy and middle age.
      RESULTS: We show that genetic effects on methylation are highly stable across the
      life course and that developmental change in the genetic contribution to
      variation in methylation occurs primarily through increases in environmental or
      stochastic effects. Though we map a large proportion of the cis-acting genetic
      variation, a much larger component of genetic effects influencing methylation are
      acting in trans. However, only 7 % of discovered mQTL are trans-effects,
      suggesting that the trans component is highly polygenic. Finally, we estimate the
      contribution of mQTL to variation in complex traits and infer that methylation
      may have a causal role consistent with an infinitesimal model in which many
      methylation sites each have a small influence, amounting to a large overall
      contribution. CONCLUSIONS: DNA methylation contains a significant heritable
      component that remains consistent across the lifespan. Our results suggest that
      the genetic component of methylation may have a causal role in complex traits.
      The database of mQTL presented here provide a rich resource for those interested
      in investigating the role of methylation in disease.

PMID- 27036882
TI  - The ESTHER hospital partnership initiative: a powerful levy for building
      capacities to combat the HIV pandemic in low-resource countries.
AB  - Partnerships between hospitals in high income countries and low resource
      countries are uniquely capable of fulfilling the tripartite needs of care,
      training, and research required to address health care crises in low resource
      countries. Of particular interest, at a time when the EBOLA crisis highlights the
      weaknesses of health systems in resource-poor settings, the institutional
      resources and expertise of hospitals can also contribute to strengthening health
      systems with long-term sustainability.We describe a partnership network between
      French Hospitals and hospitals/health structures in 19 countries that
      demonstrates the power and efficacy of health partnership in the response to the
      HIV/AIDS pandemic in sub-Saharan Africa and south East Asia. Through the ESTHER
      initiative, the partnership network currently provides capacity development, care
      and treatment to over 165,000 HIV-positive patients at 87 urban and 92 peripheral
      sites in 17 countries and enrolls 19,000 new HIV positive patients, delivers
      psychosocial services to 120 000 people and tests more than 35,000 pregnant women
      for HIV annually. It also, engages communities and assists with the development
      of a robust electronic information system.Launched in 2002, the ESTHER (Ensemble
      pour une Solidarite Therapeutique Hospitaliere En Reseau) initiative has grown
      from small projects with a focus on access to antiretroviral treatment in a
      limited number of West African countries at its outset into a large and
      comprehensive HIV/AIDS-control system in Western and Central Africa. The
      partnership's rapid achievements in the fight against HIV/AIDS, combined with the
      comprehensive and long-term approach to countries' health care needs, suggest
      that this "twinning" and medical mentoring model can and should be duplicated and
      developed to address the ever more pressing demand for response to global health
      needs in low resource countries. 

PMID- 27036881
TI  - Minicircle DNA-mediated endothelial nitric oxide synthase gene transfer enhances
      angiogenic responses of bone marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: Non-viral-based gene modification of adult stem cells with
      endothelial nitric oxide synthase (eNOS) may enhance production of nitric oxide
      and promote angiogenesis. Nitric oxide (NO) derived from endothelial cells is a
      pleiotropic diffusible gas with positive effects on maintaining vascular tone and
      promoting wound healing and angiogenesis. Adult stem cells may enhance
      angiogenesis through expression of bioactive molecules, and their genetic
      modification to express eNOS may promote NO production and subsequent cellular
      responses. METHODS: Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were
      transfected with a minicircle DNA vector expressing either green fluorescent
      protein (GFP) or eNOS. Transfected cells were analysed for eNOS expression and NO
      production and for their ability to form in vitro capillary tubules and cell
      migration. Transcriptional activity of angiogenesis-associated genes, CD31, VEGF
      A, PDGFRalpha, FGF2, and FGFR2, were analysed by quantitative polymerase chain
      reaction. RESULTS: Minicircle vectors expressing GFP (MC-GFP) were used to
      transfect HEK293T cells and rBMSCs, and were compared to a larger parental vector
      (P-GFP). MC-GFP showed significantly higher transfection in HEK293T cells (55.51
      +/- 3.3 %) and in rBMSC (18.65 +/- 1.05 %) compared to P-GFP in HEK293T cells
      (43.4 +/- 4.9 %) and rBMSC (15.21 +/- 0.22 %). MC-eNOS vectors showed higher
      transfection efficiency (21 +/- 3 %) compared to P-eNOS (9 +/- 1 %) and also
      generated higher NO levels. In vitro capillary tubule formation assays showed
      both MC-eNOS and P-eNOS gene-modified rBMSCs formed longer (14.66 +/- 0.55 mm and
      13.58 +/- 0.68 mm, respectively) and a greater number of tubules (56.33 +/- 3.51
      and 51 +/- 4, respectively) compared to controls, which was reduced with the NOS
      inhibitor L-NAME. In an in vitro wound healing assay, MC-eNOS transfected cells
      showed greater migration which was also reversed by L-NAME treatment. Finally,
      gene expression analysis in MC-eNOS transfected cells showed significant
      upregulation of the endothelial-specific marker CD31 and enhanced expression of
      VEGFA and FGF-2 and their corresponding receptors PDGFRalpha and FGFR2,
      respectively. CONCLUSIONS: A novel eNOS-expressing minicircle vector can
      efficiently transfect rBMSCs and produce sufficient NO to enhance in vitro models
      of capillary formation and cell migration with an accompanying upregulation of
      CD31, angiogenic growth factor, and receptor gene expression.

PMID- 27036884
TI  - Overall Cardiovascular Health Is Associated With All-Cause and Cardiovascular
      Disease Mortality Among Older Community-Dwelling Men and Women.
AB  - OBJECTIVE: The objective of this study was to assess the associations between
      cardiovascular health and all-cause and cardiovascular disease mortality among
      community-dwelling elderly. METHOD: Secondary data analysis was performed using
      data collected as part of the InCHIANTI cohort procedures and included 928
      participants (55% female) aged 65 years and older. Overall cardiovascular health
      was assessed using seven health behaviors and factors, scored 0 to 14, with
      higher scores indicating better cardiovascular health, modeled categorically as
      tertiles. Vitality status was ascertained using registry information. Cox
      proportional hazards models were used to examine the associations between
      cardiovascular health and all-cause and cardiovascular disease mortality.
      RESULTS: After an average follow-up of 9.1 years, better overall cardiovascular
      health (highest tertile) was inversely associated with all-cause (hazard ratio
      [HR] = 0.68, 95% confidence interval [CI] = [0.51, 0.92]) and cardiovascular
      disease mortality (HR = 0.61, 95% CI = [0.38, 0.97]) compared with the lowest
      tertile. DISCUSSION: Cardiovascular health, even in the elderly, is inversely
      associated with mortality.

PMID- 27036883
TI  - Colony-stimulating factor (CSF) 1 receptor blockade reduces inflammation in human
      and murine models of rheumatoid arthritis.
AB  - BACKGROUND: CSF-1 or IL-34 stimulation of CSF1R promotes macrophage
      differentiation, activation and osteoclastogenesis, and pharmacological
      inhibition of CSF1R is beneficial in animal models of arthritis. The objective of
      this study was to determine the relative contributions of CSF-1 and IL-34
      signaling to CSF1R in RA. METHODS: CSF-1 and IL-34 were detected by
      immunohistochemical and digital image analysis in synovial tissue from 15
      biological-naive rheumatoid arthritis (RA) , 15 psoriatic arthritis (PsA) and 7
      osteoarthritis (OA) patients . Gene expression in CSF-1- and IL-34-differentiated
      human macrophages was assessed by FACS analysis and quantitative PCR. RA synovial
      explants were incubated with CSF-1, IL-34, control antibody (Ab), or
      neutralizing/blocking Abs targeting CSF-1, IL-34, or CSF1R. The effect of a CSF1R
      blocking Ab was examined in murine collagen-induced arthritis (CIA). RESULTS: CSF
      1 (also known as M-CSF) and IL-34 expression was similar in RA and PsA synovial
      tissue, but lower in controls (P < 0.05). CSF-1 expression was observed in the
      synovial sublining, and IL-34 in the sublining and the intimal lining layer. CSF
      1 and IL-34 differentially regulated the expression of 17 of 336 inflammation
      associated genes in macrophages, including chemokines, extra-cellular matrix
      components, and matrix metalloproteinases. Exogenous CSF-1 or IL-34, or their
      independent neutralization, had no effect on RA synovial explant IL-6 production.
      Anti-CSF1R Ab significantly reduced IL-6 and other inflammatory mediator
      production in RA synovial explants, and paw swelling and joint destruction in
      CIA. CONCLUSIONS: Simultaneous inhibition of CSF1R interactions with both CSF-1
      and IL-34 suppresses inflammatory activation of RA synovial tissue and pathology
      in CIA, suggesting a novel therapeutic strategy for RA.

PMID- 27036885
TI  - Correlation of maximal inspiratory pressure to transdiaphragmatic twitch pressure
      in intensive care unit patients.
AB  - BACKGROUND: Respiratory muscle weakness contributes to respiratory failure in ICU
      patients. Unfortunately, assessment of weakness is difficult since the most
      objective test, transdiaphragmatic pressure in response to phrenic nerve
      stimulation (PdiTw), is difficult to perform. While most clinicians utilize
      maximum inspiratory pressure (Pimax) to assess strength, the relationship of this
      index to PdiTw has not been evaluated in a large ICU population. The purpose of
      the present study was to assess both PdiTw and Pimax in ICU patients to determine
      how these indices correlate with each other, what factors influence these
      indices, and how well these indices predict outcomes. METHODS: Studies were
      performed on adult mechanically ventilated patients in the University of Kentucky
      MICU (n = 60). We assessed PdiTw by measuring transdiaphragmatic pressure (Pdi)
      in response to bilateral twitch stimulation of the phrenic nerves using dual
      magnetic stimulators (Magstim 200). Pimax was determined by measuring airway
      pressure during a 30-second inspiratory occlusion. We also assessed the twitch
      and maximum force generation for diaphragms excised from control and septic mice.
      RESULTS: Both Pimax and PdiTw measurements were profoundly reduced for
      mechanically ventilated MICU patients when compared to normal reference values,
      e.g., Pimax averaged 56% of the predicted value for normal subjects. For the ICU
      population as a whole, PdiTw and Pimax values correlated with each other (r(2) =
      0.373, p < 0.001), but there was wide scatter and, as a result, PdiTw could not
      be reliably calculated from Pimax levels for individual subjects. Infection
      selectively reduced low-frequency force generation more than high-frequency force
      generation for both our mouse experiments (comparing muscle twitch to 150 Hz
      tetanic force) and for MICU patients (comparing PdiTw to Pimax). This effect of
      infection may contribute to scatter in the PdiTw to Pimax relationship. We also
      found that both PdiTw and Pimax were significantly correlated with both patient
      survival and the duration of mechanical ventilation, albeit statistically, PdiTw
      was the better predictor. CONCLUSIONS: While more difficult to measure, the PdiTw
      is a better predictor of outcomes in mechanically ventilated MICU patients than
      the Pimax. Nevertheless, for some clinical applications, the Pimax determination
      is a reasonable alternative.

PMID- 27036886
TI  - An exploration of village-level uterotonic practices in Fenerive-Est, Madagascar.
AB  - BACKGROUND: Pharmaceutical uterotonics are effective for preventing postpartum
      hemorrhage and complications related to unsafe abortion. In Madagascar, however,
      traditional birth attendants (Matrones) commonly administer medicinal teas for
      uterotonic purposes. Little is known about Matrone practices and how they might
      coincide with efforts to increase uterotonic coverage. The aims of this study
      were to: 1) identify indications for presumed uterotonic plant use by Matrones,
      2) explore uterotonic practices at the village level, and 3) describe the
      response of health practitioners to village-level uterotonic practices. METHODS:
      Twelve in-depth interviews with health practitioners, Matrones and community
      agents were conducted in local dialect. All interviews were audio-recorded,
      transcribed, and translated into English for analysis using Atlas.ti. Medicinal
      plant specimens were also collected and analyzed for the presence of uterotonic
      peptides. RESULTS: While Matrones reported to offer specific teas for uterotonic
      purposes, health practitioners discussed providing emergency care for women with
      complications associated with use of specific teas. Complications included
      retained placenta, hypertonic uterus, hemorrhage and sepsis. Chemical analysis
      indicated the presence of cysteine-rich peptides in the Dantoroa/Denturus plant
      used in some Matrones' teas. CONCLUSIONS: The presence of uterotonic peptides in
      one plant used by Matrones may indicate that Matrones intend to administer
      uterotonics for safer childbirth. This finding, combined with practitioner
      reports of complications related to some medicinal teas, points to a need for
      availability of an evidence-based uterotonic at the village level, namely,
      misoprostol pills or oxytocin in the form of uniject.

PMID- 27036887
TI  - An unusual presentation of primary hyperparathyroidism: multiple brown tumors and
      coexisting thyroid carcinoma.
AB  - We present a patient with a complex clinical picture of primary
      hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone
      metastases and concomitant multifocal papillary thyroid carcinoma with a
      metastatic central lymph node. He presented with progressively worsening right
      hip pain and restricted motion. Magnetic resonance imaging revealed multiple
      lytic lesions involving predominantly the right trochanter minor and the left
      inferior and posterior pubic rami. Biochemical tests were consistent with primary
      hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a
      single parathyroid adenoma and a thyroid nodule, preoperative cytology of which
      confirmed papillary thyroid carcinoma, as did the final surgical specimen.
      Biochemical results, regarding hyperparathyroidism, declined to normal levels and
      his complaints gradually decreased after surgery. Postoperative whole body bone
      scintigraphy showed increased tracer uptakes at multiple sites, but they were
      proved to be metabolically inactive by fluorodeoxyglucose positron emission
      tomography/computed tomography. 

PMID- 27036888
TI  - Peritoneal Cancer Index by (18)F-FDG PET/TC pre and post-hyperthermic
      intraperitoneal chemotherapy. Report of a case.
AB  - Radical cytoreductive surgery followed by hyperthermic intraperitoneal
      chemotherapy increases survival in patients with end-stage peritoneal
      carcinomatosis, and who are under palliative therapy. The Peritoneal Cancer Index
      enables the tumor burden to be quantified during surgery, as well as treatment
      planning and patient prognosis. It is obtained by combining the tumor spread in
      13 abdominal and pelvic regions with the largest tumor size. Fluorodeoxyglucose
      positron emission tomography/computed tomography is the technique of choice for
      those patients selected to undergo radical cytoreductive surgery followed by
      hyperthermic intraperitoneal chemotherapy, due to its higher detection rate of
      carcinomatosis, and since it allows extra-peritoneal disease staging. The
      simplified Peritoneal Cancer Index (9 regions defined by 2 transverse and 2
      sagittal planes) obtained by fluorodeoxyglucose positron emission
      tomography/computed tomography allows correlation with the surgical procedure,
      therefore its standardization is advisable. 

PMID- 27036889
TI  - Mosquito host choices on livestock amplifiers of Rift Valley fever virus in
      Kenya.
AB  - BACKGROUND: Animal hosts may vary in their attraction and acceptability as
      components of the host location process for assessing preference, and biting
      rates of vectors and risk of exposure to pathogens. However, these parameters
      remain poorly understood for mosquito vectors of the Rift Valley fever (RVF), an
      arboviral disease, and for a community of mosquitoes. METHODS: Using three known
      livestock amplifiers of RVF virus including sheep, goat and cattle as bait in
      enclosure traps, we investigated the host-feeding patterns for a community of
      mosquitoes in Naivasha, an endemic area of Rift Valley fever (RVF), in a
      longitudinal study for six months (June-November 2015). We estimated the
      incidence rate ratios (IRR) where mosquitoes chose cow over the other livestock
      hosts by comparing their attraction (total number collected) and engorgement rate
      (proportion freshly blood-fed) on these hosts. RESULTS: Overall, significant
      differences were observed in host preference parameters for attraction (F2,15 =
      4.1314, P = 0.037) and engorgement (F2,15 = 6.24, P = 0.01) with cow consistently
      attracting about 3-fold as many mosquitoes as those engorged on sheep
      (attraction: IRR = 2.9, 95 % CI 1.24-7.96; engorgement: IRR = 3.2, 95 % CI = 1.38
      7.38) or goat (attraction: IRR = 2.7, 95 % CI 1.18-7.16; engorgement: IRR = 3.28,
      95 % CI 1.47-7.53). However, there was no difference between the attraction
      elicited by sheep and goat (IRR = 1.08; 95 % CI 0.35-3.33 or engorgement rate
      (IRR = 0.96, 95 % CI 0.36-2.57). CONCLUSION: Despite the overall attractive
      pattern to feed preferentially on cows, the engorgement rate was clearly
      independent of the number attracted for certain mosquito species, notably among
      the flood water Aedes spp., largely incriminated previously as primary vectors of
      RVF. Our findings suggest that insecticide treated cattle (ITC) can be exploited
      in enclosure traps as contact bait in the monitoring and control of disease
      causing mosquitoes in RVF endemic areas.

PMID- 27036890
TI  - Depletion of nucleus accumbens dopamine leads to impaired reward and aversion
      processing in mice: Relevance to motivation pathologies.
AB  - Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus
      accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and
      deficient DA function could underlie motivational impairments in psychiatric
      disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for
      chronic DA depletion, principally applied in rat to study NAcc DA regulation of
      reward motivation. Given the increasing focus on studying environmental and
      genetic regulation of DA function in mouse models, it is important to establish
      the effects of 6-OHDA DA depletion in mice, in terms of reward and aversion
      processing. This mouse study investigated effects of 6-OHDA-induced NAcc DA
      depletion using the operant behavioural test battery of progressive ratio
      schedule (PRS), learned non-reward (LNR), learned helplessness (LH), treadmill,
      and in addition Pavlovian fear conditioning. 6-OHDA NAcc DA depletion, confirmed
      by ex vivo HPLC-ED, reduced operant responding: for gustatory reward under
      effortful conditions in the PRS test; to a stimulus recently associated with
      gustatory non-reward in the LNR test; to escape footshock recently experienced as
      uncontrollable in the LH test; and to avoid footshock by physical effort in the
      treadmill test. Evidence for specificity of effects to NAcc DA was provided by
      lack of effect of medial prefrontal cortex DA depletion in the LNR and LH tests.
      These findings add significantly to the evidence that NAcc DA is a major
      regulator of behavioural responding, particularly at the motivational level, to
      both reward and aversion. They demonstrate the suitability of mouse models for
      translational study of causation and reversal of pathophysiological DA function
      underlying motivation psychopathologies.

PMID- 27036891
TI  - Dopamine dynamics and cocaine sensitivity differ between striosome and matrix
      compartments of the striatum.
AB  - The striatum is typically classified according to its major output pathways,
      which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is
      also divided into striosome and matrix compartments, based on the differential
      expression of a number of proteins, including the mu opioid receptor, dopamine
      transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1).
      Numerous functional differences between the striosome and matrix compartments are
      implicated in dopamine-related neurological disorders including Parkinson's
      disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that
      electrically evoked dopamine release differs between the striosome and matrix
      compartments in a regionally-distinct manner. We further demonstrate that this
      difference is not due to differences in inhibition of dopamine release by
      dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine
      enhanced extracellular dopamine in striosomes to a greater degree than in the
      matrix and concomitantly inhibited dopamine uptake in the matrix to a greater
      degree than in striosomes. Importantly, these compartment differences in cocaine
      sensitivity were limited to the dorsal striatum. These findings demonstrate a
      level of exquisite microanatomical regulation of dopamine by the DAT in
      striosomes relative to the matrix.

PMID- 27036893
TI  - Lessons Learned from Traditional NOTES: A Historical Perspective.
AB  - The idea of natural orifice surgery was conceived by Kantsevoy and Kalloo in the
      late 1990s. A group of surgeons formed the Apollo Group in 1997. Their vision and
      mission were to impact the practice of therapeutic endoscopy through innovation
      in techniques and technologies. The concept of natural orifice surgery was
      introduced at the initial meeting held on Kiawah Island, South Carolina in 1998.
      The original concept of flexible endoscopic surgery involved per-oral passage of
      a flexible endoscope into the stomach followed by entrance into the peritoneal
      cavity via a gastrostomy. 

PMID- 27036892
TI  - Kalirin is required for BDNF-TrkB stimulated neurite outgrowth and branching.
AB  - Exogenous brain-derived neurotrophic factor (BDNF), acting through TrkB, is known
      to promote neurite formation and branching. This response to BDNF was eliminated
      by inhibition of TrkB kinase and by specific inhibition of the GEF1 domain of
      Kalirin, which activates Rac1. Neurons from Kalrn knockout mice were unable to
      activate Rac1 in response to BDNF. BDNF-triggered neurite outgrowth was abolished
      when Kalrn expression was reduced using shRNA that targets all of the major Kalrn
      isoforms, and reduced in neurons from Kalrn knockout mice. The Kalrn isoforms
      expressed early in development also include a GEF2 domain that activates RhoA.
      However, BDNF-stimulated neurite outgrowth in Kalrn knockout neurons was rescued
      by expression of Kalirin-7, which includes only the GEF1 domain but lacks the
      GEF2 domain. Dendritic morphogenesis, which requires spatially restricted,
      coordinated changes in the actin cytoskeleton and in the organization of
      microtubules, involves essential contributions from multiple Rho GEFs. Since
      Tiam1, another Rho GEF, is also required for BDNF-stimulated neurite outgrowth,
      an inhibitory fragment of Tiam1 (PHn-CC-EX) was tested and found to interfere
      with both Kalirin and Tiam1 GEF activity. The prolonged TrkB activation observed
      in response to BDNF in Kalrn knockout neurons and the altered time course and
      extent of ERK, CREB and Akt activation observed in the absence of Kalrn would be
      expected to alter the response of these neurons to other regulatory factors.

PMID- 27036894
TI  - The Evolution of "New Notes," Origins, and Future Directions.
AB  - The transformation of the submucosa into a working space provided a paradigm
      shift for endolumenal endoscopic intervention. The submucosal space can provide
      an undermining access to the removal of overlying mucosal disease. This space can
      also provide a protective mucosal barrier accommodating interventions into the
      deep layers of the gut wall and body cavities, such as the abdomen and
      mediastinum. 

PMID- 27036895
TI  - POEM, the Prototypical "New NOTES" Procedure and First Successful NOTES
      Procedure.
AB  - Peroral endoscopic myotomy (POEM) was first performed in 2008 as a novel
      treatment of achalasia. It is now performed globally, demonstrating the evolution
      of the first successful natural orifice transluminal endoscopic surgery (NOTES)
      procedure. There is extensive data demonstrating the safety and efficacy of POEM,
      and now long-term data has emerged demonstrating that the efficacy is durable.
      POEM is also being used to successfully treat diffuse esophageal spasm (DES) and
      jackhammer esophagus. With jackhammer esophagus and DES, inclusion of the lower
      esophageal sphincter in the myotomy minimizes the risk of symptom development
      from iatrogenic ineffective esophageal motility. 

PMID- 27036896
TI  - Per-Oral Pyloromyotomy (POP): An Emerging Application of Submucosal Tunneling for
      the Treatment of Refractory Gastroparesis.
AB  - A growing body of literature supports the use of laparoscopic pyloroplasty as a
      minimally invasive treatment of refractory gastroparesis that has failed
      conservative measures and for benign gastric outlet obstruction. Endoscopic
      pyloric dilation, stent placement, and Botox have been described for similar
      indications, but often with transient or mixed results. Per-oral pyloromyotomy
      has recently been proposed as an endoscopic alternative to surgical pyloroplasty
      or pylormyotomy because it is less invasive by its nature and potentially more
      durable than current endoscopic treatments. 

PMID- 27036897
TI  - Submucosal Tunneling Endoscopic Resection (STER) and Other Novel Applications of
      Submucosal Tunneling in Humans.
AB  - The submucosal tunneling technique was originally developed to provide safe
      access to the peritoneal cavity for natural orifice transluminal endoscopic
      surgery procedures. With this technique, the submucosal tunnel becomes the
      working space for partial myotomy and tumor resection. The submucosal space has
      come to represent the "third space" distinguished from gastrointestinal lumen
      (first space) and peritoneal cavity (second space). New applications continue to
      be developed and further clinical applications in the future are anticipated.
      This article summarizes the current applications of submucosal tunneling
      endoscopic resection for subepithelial tumors and describes other related uses of
      submucosal tunneling. 

PMID- 27036898
TI  - Endoscopic Full-thickness Resection (EFTR) for Gastrointestinal Subepithelial
      Tumors.
AB  - There has been booming interest in the endoscopic full-thickness resection (EFTR)
      technique since it was first described. With the advent of improved and more
      secure endoscopic closure techniques and devices, such as endoscopic suturing
      devices, endoscopists are empowered to perform more aggressive procedures than
      ever. This article focuses on the procedural technique and clinical outcomes of
      EFTR for gastrointestinal subepithelial tumors. 

PMID- 27036899
TI  - Non-Exposure, Device-Assisted Endoscopic Full-thickness Resection.
AB  - Recent developments have expanded the frontier of interventional endoscopy toward
      more extended resections following surgical principles. This article presents two
      new device-assisted techniques for endoscopic full-thickness resection in the
      upper and lower gastrointestinal tract. Both methods are nonexposure techniques
      avoiding exposure of gastrointestinal contents to the peritoneal cavity by a
      "close first-cut later" principle. The full-thickness resection device is a novel
      over-the-scope device designed for clip-assisted full-thickness resection of
      colorectal lesions. Endoscopic full-thickness resection of gastric subepithelial
      tumors can be performed after placing transmural sutures underneath the tumor
      with a suturing device originally designed for endoscopic antireflux therapy. 

PMID- 27036900
TI  - Endoscopic Submucosal Dissection (ESD) and Related Techniques as Precursors of
      "New Notes" Resection Methods for Gastric Neoplasms.
AB  - Endoscopic full-thickness resection for subepithelial tumors is one of the more
      attractive proposed methods for less-invasive transluminal surgery but remains
      challenging in terms of safety and feasibility. Currently, laparoscopic
      endoscopic cooperative surgery is thought to be a more clinically acceptable
      approach. In targeting cancers, however, more advanced nonexposure techniques are
      required to avoid the risk of iatrogenic tumor seeding. By combining these
      techniques with possible regional lymphadenectomy using sentinel node navigation
      surgery, an ideal minimally invasive, function-preserving gastric resection can
      be achieved even in possible node-positive cancers. Further development for this
      type of advanced endoscopic surgery is expected. 

PMID- 27036901
TI  - Novel NOTES Techniques and Experimental Devices for Endoscopic Full-thickness
      Resection (EFTR).
AB  - Natural orifice transluminal endoscopic surgery (NOTES), in which a flexible
      endoscope is used to perform operations that have traditionally required
      laparoscopic surgery, has garnered attention as a minimally invasive surgery that
      does not leave a surgical wound on the body. Among the various forms of NOTES,
      endoscopic full-thickness resection (EFTR) is an ultraminimally invasive
      endoscopic surgery that allows for radical resection, which is an extension of
      endoscopic submucosal dissection and involves full-thickness excision of a tumor
      of the gastrointestinal tract wall. With further development of the equipment,
      including full-thickness suture instruments, nonexposed EFTR could be a feasible
      surgical procedure. 

PMID- 27036902
TI  - Hybrid NOTES: Combined Laparo-endoscopic Full-thickness Resection Techniques.
AB  - Advances in laparoscopic surgery and therapeutic endoscopy have allowed these
      minimally destructive procedures to challenge conventional surgery. Because of
      its theoretic advantages and technical feasibility, laparoendoscopic full
      thickness resection is considered to be the most appropriate option for
      subepithelial tumor removal. Furthermore, combination of laparoscopic and
      endoscopic approaches for treatment of neoplasia can be important maneuvers for
      gastric cancer resection without contamination of the peritoneal cavity if the
      sentinel lymph node concept is established. We are certain that the use of
      laparoendoscopic full-thickness resection will provide valuable experience that
      will allow operators to safely develop endoscopic full-thickness resection
      skills. 

PMID- 27036903
TI  - Endoscopic Suturing, an Essential Enabling Technology for New NOTES
      Interventions.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) was developed as a new,
      minimally invasive approach for various interventions inside the peritoneal
      cavity. Since the first reports of NOTES animal interventions, various devices
      have been used for closure of the transluminal entrance site. This article
      reviews the most commonly used endoscopic closure devices and advantages of the
      latest generation of endoscopic suturing devices enabling reliable, surgical
      quality closure of the full-thickness gastrointestinal wall defects. 

PMID- 27036904
TI  - New NOTES Clinical Training and Program Development.
AB  - Natural orifice translumenal endoscopic surgery (NOTES) is an intense area of
      research, and is arguably the most significant endoscopic innovation of this
      decade. Training for new NOTES is a relatively long, encompassing advanced
      endoscopy training, mastery of endoscopic dexterity within the narrow submucosal
      or "third space" with an in-depth understanding of the tissue planes. Proficiency
      with new closure and hemostatic devices is also essential. Few institutions
      worldwide can provide all the cognitive and technical elements essential to train
      new NOTES trainees. Trainees may need to spend time across several institutions
      to ensure safe and effective practice of new NOTES. 

PMID- 27036906
TI  - A Western Perspective on "New NOTES" from POEM to Full-thickness Resection and
      Beyond.
AB  - Most new natural orifice translumenal endoscopic surgery procedures originated in
      Asia; therefore, most data come from operators and a health care environment
      different from those in the West. We provide a Western perspective. We discuss
      East-West differences; review areas in which the United States is leading the
      way; and discuss the vagaries of coding and reimbursement. In the United States,
      reimbursement remains problematic. A Current Procedural Terminology code for
      peroral endoscopic myotomy is inevitable given the rapidly accumulating
      overwhelmingly positive outcomes data. However, coordinated efforts may help
      accelerate the process. 

PMID- 27036905
TI  - Pre-clinical Training for New Notes Procedures: From Ex-vivo Models to Virtual
      Reality Simulators.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is a newer field of
      endoscopic surgery that allows for scarless treatment of pathologic entities,
      using novel transluminal approaches. There has been a shift of focus from a
      clinical and research standpoint from the development and dissemination of "first
      generation" NOTES procedures to "new NOTES" procedures that traverse the mucosa
      of luminal structures, yet do not stray far into the peritoneal cavity. It has
      been a challenge to find appropriate and effective ways to train
      gastroenterologists and surgeons in these novel approaches. We review the
      importance of simulation in training and discuss available simulation options. 

PMID- 27036907
TI  - The New NOTES Expands Interventional Endoscopy.

PMID- 27036908
TI  - The New NOTES: More "E" and Less "S" Leads to Success!

PMID- 27036910
TI  - Polymicrobial vertebral osteomyelitis after oesophageal biopsy: a case report.
AB  - BACKGROUND: While most cases of polymicrobial vertebral osteomyelitis are
      secondary to hematogenous seeding, direct inoculation during spinal surgery and
      contiguous spread from adjacent soft tissue are also potential routes whereby
      pathogens may infect the spine. CASE PRESENTATION: A 74 year-old man presented
      with an exacerbation of back pain after a fall. His past medical history included
      hepatocellular and oesophageal carcinoma. Three months earlier he had undergone
      an endoscopic biopsy of the oesophagus for routine follow-up of his oesophagus
      carcinoma. He also underwent a vertebroplasty due to suspected pathologic
      fracture. On admission to hospital, magnetic resonance imaging revealed an
      infiltrative process at the level of the 5th and 6th thoracic vertebrae. Blood
      cultures were positive for both Streptococcus mitis and Gemella morbillorum.
      During his course of antibiotic therapy he developed an abscess at the level of
      8th thoracic vertebrae and culture of this abscess grew Candida albicans. He was
      treated with antibiotics and antifungal drugs and recovered fully. CONCLUSION:
      Vertebral osteomyelitis may be caused by direct spread following an oesophageal
      procedure. Microbiological diagnosis is essential to target the specific
      pathogen, especially in cases of polymicrobial infection.

PMID- 27036911
TI  - The C-Terminal Acidic Region of Calreticulin Mediates Phosphatidylserine Binding
      and Apoptotic Cell Phagocytosis.
AB  - Calreticulin is a calcium-binding chaperone that is normally localized in the
      endoplasmic reticulum. Calreticulin is detectable on the surface of apoptotic
      cells under some apoptosis-inducing conditions, where it promotes the
      phagocytosis and immunogenicity of dying cells. However, the precise mechanism by
      which calreticulin, a soluble protein, localizes to the outer surface of the
      plasma membrane of dying cells is unknown, as are the molecular mechanisms that
      are relevant to calreticulin-induced cellular phagocytosis. Calreticulin
      comprises three distinct structural domains: a globular domain, an extended arm
      like P-domain, and a C-terminal acidic region containing multiple low-affinity
      calcium binding sites. We show that calreticulin, via its C-terminal acidic
      region, preferentially interacts with phosphatidylserine (PS) compared with other
      phospholipids and that this interaction is calcium dependent. Additionally,
      exogenous calreticulin binds apoptotic cells via a higher-affinity calcium
      dependent mode that is acidic region dependent. Exogenous calreticulin also binds
      live cells, including macrophages, via a second, lower-affinity P-domain and
      globular domain-dependent, but calcium-independent binding mode that likely
      involves its generic polypeptide binding site. Truncation constructs lacking the
      acidic region or arm-like P-domain of calreticulin are impaired in their
      abilities to induce apoptotic cell phagocytosis by murine peritoneal macrophages.
      Taken together, the results of this investigation provide the first molecular
      insights into the phospholipid binding site of calreticulin as a key anchor point
      for the cell surface expression of calreticulin on apoptotic cells. These
      findings also support a role for calreticulin as a PS-bridging molecule that
      cooperates with other PS-binding factors to promote the phagocytosis of apoptotic
      cells.

PMID- 27036912
TI  - Maternal Antibiotic Treatment Impacts Development of the Neonatal Intestinal
      Microbiome and Antiviral Immunity.
AB  - Microbial colonization of the infant gastrointestinal tract (GIT) begins at
      birth, is shaped by the maternal microbiota, and is profoundly altered by
      antibiotic treatment. Antibiotic treatment of mothers during pregnancy influences
      colonization of the GIT microbiota of their infants. The role of the GIT
      microbiota in regulating adaptive immune function against systemic viral
      infections during infancy remains undefined. We used a mouse model of perinatal
      antibiotic exposure to examine the effect of GIT microbial dysbiosis on infant
      CD8(+) T cell-mediated antiviral immunity. Maternal antibiotic treatment/treated
      (MAT) during pregnancy and lactation resulted in profound alterations in the
      composition of the GIT microbiota in mothers and infants. Streptococcus spp.
      dominated the GIT microbiota of MAT mothers, whereas Enterococcus faecalis
      predominated within the MAT infant GIT. MAT infant mice subsequently exhibited
      increased and accelerated mortality following vaccinia virus infection. Ag
      specific IFN-gamma-producing CD8(+) T cells were reduced in sublethally infected
      MAT infant mice. MAT CD8(+) T cells from uninfected infant mice also demonstrated
      a reduced capacity to sustain IFN-gamma production following in vitro activation.
      We additionally determined that control infant mice became more susceptible to
      infection if they were born in an animal facility using stricter standards of
      hygiene. These data indicate that undisturbed colonization and progression of the
      GIT microbiota during infancy are necessary to promote robust adaptive antiviral
      immune responses.

PMID- 27036913
TI  - Identification of Immune Effectors Essential to the Control of Primary and
      Secondary Intranasal Infection with Brucella melitensis in Mice.
AB  - The mucosal immune system represents the first line of defense against Brucella
      infection in nature. We used genetically deficient mice to identify the
      lymphocytes and signaling pathways implicated in the control of primary and
      secondary intranasal infection with B. melitensis Our analysis of primary
      infection demonstrated that the effectors implicated differ at the early and late
      stages and are dependent on the organ. TCR-delta, TAP1, and IL-17RA deficiency
      specifically affects early control of Brucella in the lungs, whereas MHC class II
      (MHCII) and IFN-gammaR deficiency impairs late control in the lungs, spleen, and
      liver. Interestingly, IL-12p35(-/-) mice display enhanced Brucella growth in the
      spleen but not in the lungs or liver. Secondary intranasal infections are
      efficiently contained in the lung. In contrast to an i.p. infectious model, in
      which IL-12p35, MHCII, and B cells are strictly required for the control of
      secondary infection, we observed that only TCR-beta deficiency or simultaneous
      neutralization of IL-12p35- and IL-17A-dependent pathways impairs the memory
      protective response against a secondary intranasal infection. Protection is not
      affected by TCR-delta, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency,
      suggesting that CD4(+) and CD8(+) alpha/beta(+) T cells are sufficient to mount a
      protective immune response and that an IL-17A-mediated response can compensate
      for the partial deficiency of an IFN-gamma-mediated response to control a
      Brucella challenge. These findings demonstrate that the nature of the protective
      memory response depends closely on the route of infection and highlights the role
      of IFN-gamma-and IL-17RA-mediated responses in the control of mucosal infection
      by Brucella.

PMID- 27036914
TI  - A Functionalized Sphingolipid Analogue for Studying Redistribution during
      Activation in Living T Cells.
AB  - Sphingolipids are major components of the plasma membrane. In particular,
      ceramide serves as an essential building hub for complex sphingolipids, but also
      as an organizer of membrane domains segregating receptors and signalosomes.
      Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation
      of a variety of receptors is the predominant source of ceramides released at the
      plasma membrane. This especially applies to T lymphocytes where formation of
      ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide
      release and redistribution occur very rapidly in response to receptor ligation,
      novel tools to further study these processes in living T cells are urgently
      needed. To meet this demand, we synthesized nontoxic, azido-functionalized
      ceramides allowing for bio-orthogonal click-reactions to fluorescently label
      incorporated ceramides, and thus investigate formation of ceramide-enriched
      domains. Azido-functionalized C6-ceramides were incorporated into and localized
      within plasma membrane microdomains and proximal vesicles in T cells. They
      segregated into clusters after TCR, and especially CD28 ligation, indicating
      efficient sorting into plasma membrane domains associated with T cell activation;
      this was abolished upon sphingomyelinase inhibition. Importantly, T cell
      activation was not abrogated upon incorporation of the compound, which was
      efficiently excluded from the immune synapse center as has previously been seen
      in Ab-based studies using fixed cells. Therefore, the functionalized ceramides
      are novel, highly potent tools to study the subcellular redistribution of
      ceramides in the course of T cell activation. Moreover, they will certainly also
      be generally applicable to studies addressing rapid stimulation-mediated ceramide
      release in living cells.

PMID- 27036915
TI  - Target Density, Not Affinity or Avidity of Antigen Recognition, Determines
      Adoptive T Cell Therapy Outcomes in a Mouse Lymphoma Model.
AB  - Adoptive T cell therapy (ACT) with antitumor CTL is a promising and tailored
      treatment against cancer. We investigated the role played by the affinity and
      avidity of the interaction between the tumor and the CTL on the outcome of ACT
      against a mouse non-Hodgkin B cell lymphoma that expresses OVA as a model
      neoantigen. ACT was assessed under conditions where antitumor CTL expressed TCR
      of varying affinity for OVA. We also assessed conditions where the avidity of Ag
      recognition varied because the lymphoma cells expressed high or low levels of
      OVA. Efficient eradication of small tumor burdens was achieved by high- or low
      affinity CTL. Tumors expressing low levels of OVA could also be eliminated.
      However, ACT against large tumor burdens was unsuccessful, accompanied by CTL
      deletion and functional impairment. This negative outcome was not prevented by
      lowering the affinity of the CTL or the expression of OVA in the lymphoma. Thus,
      tumor burden, rather than CTL affinity or avidity, appears to be the main
      determinant of ACT outcomes in our lymphoma model. Insofar as our results can be
      extrapolated to the clinical setting, they imply that the range of CTL and tumor
      associated Ag combinations that may be effectively harnessed in ACT against
      lymphoma may be wider than generally assumed. CTL expressing low-affinity TCR may
      be effective against lymphoma, and lowly expressed tumor-associated Ag should be
      considered as potential targets, but tumor reduction should always be implemented
      before infusion of the CTL.

PMID- 27036916
TI  - TNF-alpha and Macrophages Are Critical for Respiratory Syncytial Virus-Induced
      Exacerbations in a Mouse Model of Allergic Airways Disease.
AB  - Viral respiratory infections trigger severe exacerbations of asthma, worsen
      disease symptoms, and impair lung function. To investigate the mechanisms
      underlying viral exacerbation, we established a mouse model of respiratory
      syncytial virus (RSV)-induced exacerbation after allergen sensitization and
      challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in
      significantly increased airway hyperresponsiveness (AHR) and macrophage and
      neutrophil lung infiltration. Exacerbation was accompanied by increased levels of
      inflammatory cytokines (including TNF-alpha, MCP-1, and keratinocyte-derived
      protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated
      mice exposed to UV-inactivated RSV. Dexamethasone treatment completely inhibited
      all features of allergic disease, including AHR and eosinophil infiltration, in
      uninfected OVA-sensitized/challenged mice. Conversely, dexamethasone treatment
      following RSV-induced exacerbation only partially suppressed AHR and failed to
      dampen macrophage and neutrophil infiltration or inflammatory cytokine production
      (TNF-alpha, MCP-1, and KC). This mimics clinical observations in patients with
      exacerbations, which is associated with increased neutrophils and often poorly
      responds to corticosteroid therapy. Interestingly, we also observed increased TNF
      alpha levels in sputum samples from patients with neutrophilic asthma. Although
      RSV-induced exacerbation was resistant to steroid treatment, inhibition of TNF
      alpha and MCP-1 function or depletion of macrophages suppressed features of
      disease, including AHR and macrophage and neutrophil infiltration. Our findings
      highlight critical roles for macrophages and inflammatory cytokines (including
      TNF-alpha and MCP-1) in viral-induced exacerbation of asthma and suggest
      examination of these pathways as novel therapeutic approaches for disease
      management.

PMID- 27036918
TI  - 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in
      Patients With Coronary Artery Disease: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

PMID- 27036917
TI  - Lipopolysaccharide-Induced Chorioamnionitis Promotes IL-1-Dependent Inflammatory
      FOXP3+ CD4+ T Cells in the Fetal Rhesus Macaque.
AB  - Chorioamnionitis is associated with preterm labor and fetal inflammatory response
      syndrome (FIRS), causing fetal organ injury and morbidity, particularly in
      extremely premature infants. However, the effects of inflammation on the fetal
      immune system remain poorly understood, due to the difficulty of studying immune
      development in infants. Therefore, we used the model of intra-amniotic LPS
      administered at ~80% gestation in rhesus monkeys to cause chorioamnionitis and
      FIRS that is similar in human pathology. Importantly, the frequency of IL-17(+)
      and IL-22(+) CD4(+) T cells increased in the spleen of LPS-exposed fetuses,
      whereas regulatory T cell (Treg) frequency decreased. These changes persisted for
      at least 48 h. Notably, Th17 cytokines were predominantly expressed by
      FOXP3(+)CD4(+) T cells and not by their FOXP3(-) counterparts. Bifunctional IL
      17(+)FOXP3(+) exhibited a phenotype of inflammatory Tregs (RORc(High/+),
      Helios(Low/-), IL-2(+), IFN-gamma(+), and IL-8(+)) compared with typical FOXP3(+)
      cells. Diminished splenic Treg frequency in LPS-exposed fetuses was associated
      with inadequate Treg generation in the thymus. Mechanistically, the emergence of
      inflammatory Tregs was largely dependent on IL-1 signaling. However, blockage of
      IL-1R signaling did not abolish the deleterious effects of LPS on Treg frequency
      in the thymus or spleen. Collectively, we demonstrate that a prenatal
      inflammatory environment leads to inadequate Treg generation in the thymus with a
      switch of splenic Tregs toward an inflammatory phenotype. Both processes likely
      contribute to the pathogenesis of chorioamnionitis. Approaches to manipulate Treg
      numbers and function could thus be useful therapeutically to alleviate FIRS in
      preterm infants.

PMID- 27036919
TI  - Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA
      Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients
      With Coronary Artery Disease: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
AB  - BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after
      implantation of newer-generation drug-eluting stents (DES) remains uncertain.
      Similarly, questions remain about the role of DAPT in long-term therapy of stable
      post-myocardial infarction (MI) patients. AIM: Our objective was to compare the
      incidence of death, major hemorrhage, MI, stent thrombosis, and major adverse
      cardiac events in patients randomized to prolonged or short-course DAPT after
      implantation of newer-generation DES and in secondary prevention after MI.
      METHODS: We used traditional frequentist statistical and Bayesian approaches to
      address the following questions: Q1) What is the minimum duration of DAPT
      required after DES implantation? Q2) What is the clinical benefit of prolonging
      DAPT up to 18 to 48 months? Q3) What is the clinical effect of DAPT in stable
      patients who are >1 year past an MI? RESULTS: We reviewed evidence from 11
      randomized controlled trials (RCTs) that enrolled 33 051 patients who received
      predominantly newer-generation DES to answer: A1) Use of DAPT for 12 months, as
      compared with use for 3 to 6 months, resulted in no significant differences in
      incidence of death (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.85 to
      1.63), major hemorrhage (OR: 1.65; 95% CI: 0.97 to 2.82), MI (OR: 0.87; 95% CI:
      0.65 to 1.18), or stent thrombosis (OR: 0.87; 95% CI: 0.49 to 1.55). Bayesian
      models confirmed the primary analysis. A2) Use of DAPT for 18 to 48 months,
      compared with use for 6 to 12 months, was associated with no difference in
      incidence of all-cause death (OR: 1.14; 95% CI: 0.92 to 1.42) but was associated
      with increased major hemorrhage (OR: 1.58; 95% CI: 1.20 to 2.09), decreased MI
      (OR: 0.67; 95% CI: 0.47 to 0.95), and decreased stent thrombosis (OR: 0.45; 95%
      CI: 0.24 to 0.74). A risk-benefit analysis found 3 fewer stent thromboses (95%
      CI: 2 to 5) and 6 fewer MIs (95% CI: 2 to 11) but 5 more major bleeds (95% CI: 3
      to 9) per 1000 patients treated with prolonged DAPT per year. Post hoc analyses
      provided weak evidence of increased mortality with prolonged DAPT. We reviewed
      evidence from 1 RCT of 21 162 patients and a post hoc analysis of 1 RCT of 15 603
      patients to answer: A3): Use of DAPT >1 year after MI reduced the composite risk
      of cardiovascular death, MI, or stroke (hazard ratio: 0.84; 95% CI: 0.74 to 0.95)
      but increased major bleeding (hazard ratio: 2.32; 95% CI: 1.68 to 3.21). A meta
      analysis and a post hoc analysis of an RCT in patients with stable cardiovascular
      disease produced similar findings. CONCLUSIONS: The primary analysis provides
      moderately strong evidence that prolonged DAPT after implantation of newer
      generation DES entails a tradeoff between reductions in stent thrombosis and MI
      and increases in major hemorrhage. Secondary analyses provide weak evidence of
      increased mortality with prolonged DAPT after DES implantation. In patients whose
      coronary thrombotic risk was defined by a prior MI rather than by DES
      implantation, the primary analysis provides moderately strong evidence of reduced
      cardiovascular events at the expense of increased bleeding.

PMID- 27036920
TI  - The Use of a Closed-Suction Drain in Revision Knee Arthroplasty May Not Be
      Necessary: A Prospective Randomized Study.
AB  - BACKGROUND: The benefit of suction drains (SD) for the first 24-48 hours
      following joint replacement surgery is controversial. We aimed to determine if
      there is any difference in the early outcome of revision TKA when performed with,
      or without SD. METHODS: 83 cases indicated for revision knee arthroplasty were
      randomized to receive (42) or not receive (41) a deep intra-articlular drain.
      First-stage revisions for treating periprosthetic infection were excluded.
      Patients were statistically compared for demographic parameters, early
      complications and early knee functional outcome. The assessed outcomes included
      total blood loss, number of transfusions, fever and wound complication rate at 24
      months follow-up. In addition, the change in knee society score at 12 weeks
      postoperatively was compared between the groups. RESULTS: There were no
      significant difference in demographic factors, wound complications, knee scores
      at 12 weeks and infection rate 24 months after surgery in either group. Average
      blood loss was 1856ml and 1533ml for the drain and no drain groups, respectively
      (P value=0.0470). The need for transfusion was significantly less in the no-drain
      group with an average of 0.15 unit/patient as compared to an average 0.37
      unit/patient for the drain group (P value=0.0432). CONCLUSION: We were unable to
      find a point of superiority for using a drain for revision knee arthroplasty.
      Future studies with longer follow-up and larger population of patients are needed
      to make a valid conclusion.

PMID- 27036921
TI  - Primary Care Physician and Patient Perceptions of Reimbursement for Total Knee
      and Hip Replacement.
AB  - BACKGROUND: The opinions of nonspecialists and patients will be important to
      determining reimbursements for specialists such as orthopedic surgeons. In
      addition, primary care physician (PCP) perceptions of reimbursements may affect
      utilization of orthopedic services. METHODS: We distributed a web-based survey to
      PCPs, asking how much they believed orthopedic surgeons were reimbursed for total
      hip arthroplasty (THA) and total knee arthroplasty (TKA). We also proctored a
      paper-based survey to postoperative patients, asking how much orthopedic surgeons
      should be reimbursed. RESULTS: There was a significant difference between
      perceived and actual reimbursement values for THA and TKA. Hospital-affiliated
      PCPs estimated higher reimbursements for both THA ($1657 vs $838, P < .0001 for
      Medicaid and $2246 vs $1515, P = .018 for Medicare) and TKA ($1260 vs $903, P =
      .052 for Medicaid and $2022 vs $1514, P = .049 for Medicare). Similarly, larger
      practices estimated higher reimbursements for both THA ($1861 vs $838, P < .0001
      for Medicaid and $2635 vs $1515, P = .004 for Medicare) and TKA ($1583 vs $903, P
      = .005 for Medicaid and $2380 vs $1514, P = .011 for Medicare). Compared to PCPs,
      patients estimated that orthopedic surgeons should be paid 4 times higher for
      both THA ($9787 vs $2235, P < .0001) and TKA ($9088 vs $2134, P < .0001).
      CONCLUSION: PCPs believe that reimbursements for orthopedic procedures are higher
      than actual values. The effect that these perceptions will have on efforts at
      cost reform and utilization of orthopedic services requires further study.

PMID- 27036922
TI  - Significantly Poor Outcomes of Total Hip Arthroplasty After Failed Periacetabular
      Osteotomy.
AB  - BACKGROUND: Periacetabular osteotomy (PAO) is an effective treatment for
      preosteoarthritis and early osteoarthritis in young and active patients with hip
      dysplasia. However, conversion to total hip arthroplasty (THA) for failed PAO is
      difficult owing to morphologic changes. The objective of the present study was to
      investigate outcomes of patients who underwent THA for failed PAO. METHODS: We
      performed a case-control study. The participants were 48 patients (52 hips) who
      underwent THA after PAO (the osteotomy group); type of PAO was eccentric
      rotational acetabular osteotomy in 36 hips and rotational acetabular osteotomy in
      16 hips. These patients had a mean age at surgery of 56.5 years and underwent
      postoperative follow-up for a mean period of 5.4 years. For the control group,
      after matching age, gender, and time of surgery, we included 96 patients (104
      joints) who underwent primary THA for hip dysplasia. RESULTS: The 2 groups
      demonstrated no significant difference in the preoperative Harris Hip Score.
      However, the osteotomy group demonstrated a significantly poor Harris Hip Score
      at the last follow-up, with particularly low scores for gait and activity. The
      osteotomy group demonstrated significantly poor range of motion at the last
      follow-up. Although neither group had any cases of revision surgery, both groups
      had 1 case of postoperative dislocation. Considering socket placement in
      Lewinnek's safe zone, the osteotomy group had significantly poorer results
      compared to that obtained after primary THA. CONCLUSION: The therapeutic outcomes
      and socket positioning for THA after PAO were poorer compared to those of primary
      THA.

PMID- 27036923
TI  - Diabetes is a Risk Factor for Restricted Range of Motion and Poor Clinical
      Outcome After Total Knee Arthroplasty.
AB  - BACKGROUND: We investigated the effects of diabetes mellitus on knee range of
      motion, muscle strength, and functional outcome after total knee arthroplasty.
      METHODS: A total of 20 patients with type 2 diabetes and 20 patients without
      diabetes matched for age, body mass index, knee range of motion, and muscle
      strength at baseline participated in this study. We examined knee range of motion
      and muscle strength and assessed functional activities using the new Knee Society
      Score questionnaire for each patient 1 month preoperatively and at 6 and 12
      months postoperatively. RESULTS: Patients with diabetes had significantly lower
      knee flexion and smaller improvements in the new Knee Society Score than patients
      without diabetes. CONCLUSION: Our results suggest that clinicians should treat
      and monitor patients with diabetes closely to prevent restricted knee range of
      motion and poorer functional recovery after total knee arthroplasty.

PMID- 27036924
TI  - You Want a Successful Bundle: What About Post-discharge Care?
AB  - BACKGROUND: The postacute care strategies after total joint arthroplasty,
      including the use of postacute rehabilitation centers and home therapy services
      are associated with different costs. Providers in bundled payment programs are
      incentivized to use the most cost-effective strategies while maintaining quality
      and value for patients. METHODS: We discuss the impact of postacute care on a
      bundled payment program and strategies for optimizing the value of this component
      of the care episode using the experience of a large academic urban medical center
      participating in the Centers for Medicare and Medicaid Services Bundled Payments
      for Care Improvement Initiative. RESULTS: The results of this analysis show that
      efforts to increase the use of home discharge and decrease the use of postacute
      facilities after elective primary total hip and knee arthroplasties can lead to
      cost-effective quality care with a high degree of patient satisfaction.
      CONCLUSION: The postdischarge period is a significant part of a bundled payment
      episode. To manage a successful bundled payment program in total joint
      arthroplasty, significant efforts to coordinate care during this episode are
      needed for patients to receive quality care that meets their expectations.

PMID- 27036925
TI  - Clinical Analysis of Propionibacterium acnes Infection After Total Knee
      Arthroplasty.
AB  - BACKGROUND: Propionibacterium acnes is a common cause of upper extremity
      arthroplasty infection and usually presents in an indolent subacute fashion. It
      is not well described how total knee arthroplasty (TKA) patients infected with P
      acnes present. METHODS: We retrospectively compared patients undergoing revision
      TKA for infection from P acnes and methicillin-sensitive Staphylococcal aureus
      (MSSA) in our institutional infection database. Patients were classified as
      having a periprosthetic joint infection based on the Musculoskeletal Infection
      Society criteria and were excluded if they had a polymicrobial culture. Patient
      demographics, preoperative laboratory values, microbiology data, and synovial
      fluid white blood cell (WBC) counts were analyzed. RESULTS: Sixteen patients with
      a P acnes and 30 with an MSSA TKA periprosthetic joint infection were identified.
      Median erythrocyte sedimentation rate was significantly higher in the MSSA group
      compared to the P acnes group (56.0 mm/h; interquartile range [IQR], 44.3-72.9 vs
      23.0 mm/h; IQR, 18.5-52.0; respectively, P = .03) as were C-reactive protein
      levels (5.9 mg/dL; IQR, 3.7-26.9 vs 2.0 mg/dL; IQR, 0.5-14.0; respectively, P =
      .04). WBC count, synovial fluid WBC, and percentage of synovial polymorphonuclear
      cells were similar between groups. Mean time to culture was 8.3 +/- 2.0 days in
      the P acnes group and 1.8 +/- 0.8 days in the MSSA group. CONCLUSION: P acnes TKA
      infections are associated with more acute inflammatory symptoms than typically
      appreciated, and long hold anaerobic cultures up to 14 days are necessary to
      accurately identify this organism as the causative agent of TKA periprosthetic
      infection.

PMID- 27036926
TI  - Internalization and synaptogenic effect of GH in retinal ganglion cells (RGCs).
AB  - In the chicken embryo, GH gene expression occurs in the neural retina and retinal
      GH promotes cell survival and induces axonal growth of retinal ganglion cells.
      Neuroretinal GH is therefore of functional importance before the appearance of
      somatotrophs and the onset of pituitary GH secretion to the peripheral plasma (at
      ED15-17). Endocrine actions of pituitary GH in the development and function of
      the chicken embryo eye are, however, unknown. This possibility has therefore been
      investigated in ED15 embryos and using the quail neuroretinal derived cell line
      (QNR/D). During this research, we studied for the first time, the coexistence of
      exogenous (endocrine) and local GH (autocrine/paracrine) in retinal ganglion
      cells (RGCs). In ovo systemic injections of Cy3-labeled GH demonstrated that GH
      in the embryo bloodstream was translocated into the neural retina and
      internalized into RGC's. Pituitary GH may therefore be functionally involved in
      retinal development during late embryogenesis. Cy3-labelled GH was similarly
      internalized into QNR/D cells after its addition into incubation media. The
      uptake of exogenous GH was by a receptor-mediated mechanism and maximal after 30
      60min. The exogenous (endocrine) GH induced STAT5 phosphorylation and increased
      growth associated protein 43 (GAP43) and SNAP-25 immunoreactivity. Ex ovo
      intravitreal injections of Cy3-GH in ED12 embryos resulted in GH internalization
      and STAT5 activation. Interestingly, the CY3-labeled GH accumulated in
      perinuclear regions of the QNR/D cells, but was not found in the cytoplasm of
      neurite outgrowths, in which endogenous retinal GH is located. This suggests that
      exogenous (endocrine) and local (autocrine/paracrine) GH are both involved in
      retinal function in late embryogenesis but they co-exist in separate
      intracellular compartments within retinal ganglion cells.

PMID- 27036927
TI  - Occipital Sinus Thrombosis: An Exceptional Case Report.
AB  - BACKGROUND: Variations of the dural venous sinuses may result in inaccurate
      imaging interpretation or complications during surgical approaches. One variation
      of the dural venous sinuses reported infrequently in the literature is the
      occipital sinus. We report an exceptional case of occipital sinus thrombosis.
      CASE REPORT: A 48-year-old right-handed man with a 5-month history of
      hypertension and chronic renal failure presented with cephalalgia, vomiting, and
      blurred vision evolving over 48 hours. Neurological examination revealed
      papillary edema stage 1 with no others abnormalities. An initial brain computed
      tomography (CT) scan performed was normal. The opening pressure of cerebrospinal
      fluid (CSF) was 35 cmH2O with normal level of protein and no hypercellularity in
      CSF analysis. The evolution was marked by the occurrence of generalized tonic
      clonic seizure. A second CT scan performed showed a hyperdensity of the occipital
      sinus. Magnetic resonance imaging and magnetic resonance venography studies
      confirmed the diagnosis with highlighting the thrombosis of the occipital sinus
      in association to an ectasia of the torcular. The patient received adequate
      anticoagulation for 6 months in association to antiepileptic drugs with a good
      evolution. DISCUSSION: According to our review, such a thrombosis must be a rare
      condition, because our literature search has shown a lack of any report
      describing this condition. Herein, we review the anatomy of the occipital sinus
      and we illustrate the characteristics of this unusual thrombosis with multiple
      imaging modalities. CONCLUSION: Understanding of the cerebral venous anatomy and
      recognition of venous variations essentially help when dealing with a pathology,
      which presents along with a particular venous variation, no matter how rare this
      combination is.

PMID- 27036928
TI  - A survey of critical care nurses' knowledge of intra-abdominal hypertension and
      abdominal compartment syndrome.
AB  - BACKGROUND: Intra-abdominal hypertension and abdominal compartment syndrome are
      potentially life threatening conditions. Critical care nurses need to understand
      the factors that predispose patients to intra-abdominal hypertension (IAH) and
      abdominal compartment syndrome (ACS). Predicting and managing IAH and ACS are
      important to improve health outcomes. AIM: The aim of this paper was to (1)
      assess the knowledge of Australian critical care nurses about current IAH and ACS
      practice guidelines, measurement techniques, predictors for the development of
      IAH and ACS and (2) identify barriers in recognizing IAH, ACS and measuring IAP.
      METHODS: Between October 2014 and April 2015 86 registered nurses employed in the
      area of critical care were recruited via the form to participate in an on-line,
      19-item questionnaire. The survey was distributed to critical care nurses via the
      Australian College of Critical Care Nurses (ACCCN) mailing list and directly to
      intensive care units via The majority of participants were women (n=62) all
      participants were registered nurses employed in critical care the response rate
      was 3.2%. The study design was used to establish demographic data, employment
      data, and individuals' knowledge related to IAH and ACS. Participants had the
      option to write hand written responses in addition to selecting a closed question
      response. RESULTS: The results showed that most survey participants were able to
      identify some obvious causes of IAH. However, less than 20% were able to
      recognize less apparent indices of risk. A lack of education related to IAP
      monitoring was identified by nearly half (44.2%) of respondents as the primary
      barrier to monitoring IAP. CONCLUSION: Critical care clinicians' knowledge of IAH
      and ACS is generally low in the areas of presentation and outcomes of IAH and ACS
      requiring tailored and targeted educational interventions.

PMID- 27036929
TI  - Genetically predicted 17beta-estradiol, cognitive function and depressive
      symptoms in women: A Mendelian randomization in the Guangzhou Biobank Cohort
      Study.
AB  - OBJECTIVE: The role of estrogen in cognitive function and depressive symptoms is
      controversial due to discrepancies between results from randomized controlled
      trials (RCT) and observational studies. Mendelian randomization analysis may
      provide further insights concerning the role of estrogen in these outcomes as it
      assesses the effect of lifelong endogenous exposure but is less vulnerable to
      confounding than observational studies. METHOD: We used separate sample
      instrumental variable analysis to estimate the association of log 17beta
      estradiol with cognitive function (Delayed 10 word recall, and Mini Mental State
      Examination (MMSE)) and depressive symptoms (Geriatric Depression Scale (GDS)) in
      older Chinese women of the Guangzhou Biobank Cohort Study (GBCS, n=3086). The
      estimate was derived based on the Wald estimator, the ratio of the association of
      genetic determinants (rs1008805 and rs2175898) of log 17beta-estradiol with
      cognitive function and depressive symptoms in GBCS and the association of log
      17beta-estradiol with genetic determinants in the sample of young women in Hong
      Kong (n=236). RESULTS: Genetically predicted 17beta-estradiol was not associated
      with delayed 10-word recall (0.42 words per log increase in 17beta-estradiol
      (pmol/L), 95% confidence interval (CI) -0.49 to 1.34) MMSE (0.39 per log increase
      in 17beta-estradiol (pmol/L), 95% CI -0.87 to 1.65) or GDS (0.24 per log increase
      in 17beta-estradiol (pmol/L), 95% CI -0.57 to 1.05). CONCLUSION: These results
      were largely consistent with evidence from RCTs and did not show any beneficial
      effect of estrogen on cognitive function and depressive symptoms. However, larger
      Mendelian randomization analyses are needed to identify any minor effects.

PMID- 27036930
TI  - Anesthesia with topical lidocaine hydrochloride gauzes in acute traumatic wounds
      in triage, a pilot study.
AB  - BACKGROUND: Topical application of lidocaine in wounds has been studied in
      combination with vasoconstrictive additives, but the effect without these
      additives is unknown. The objective was to examine use of lidocaine-soaked gauzes
      without vasoconstrictive agents, in traumatic wounds in adult patients, applied
      in triage. METHODS: A prospective pilot study was performed during 6 weeks in the
      Emergency Department of a level 1 trauma center. Wounds of consecutive adult
      patients were treated with a nursing protocol, consisting of lidocaine
      hydrochloride administration directly into the wound and leaving a lidocaine
      soaked gauze, until wound treatment. Primary outcome was need for infiltration
      anesthesia. Secondary outcomes were Numerical Rating Scale (NRS) pain scores,
      adverse events and patient and physician satisfaction. RESULTS: Forty patients
      with a traumatic wound were included, 85% male with a wound on the arm. Thirty
      seven patients needed a painful procedure as wound treatment. When suturing was
      necessary, 77% required additional infiltration anesthesia. Mean NRS pain scores
      decreased from 3.3 to 2.2 after application of the lidocaine gauze. No adverse
      events were recorded. Of the patients, 60% were satisfied with use of the
      lidocaine gauzes, compared to 40% of physicians. CONCLUSION: Lidocaine
      hydrochloride (2%) gauzes without vasoconstrictive additives cannot replace
      infiltration anesthesia in traumatic wounds.

PMID- 27036931
TI  - Small Molecule Inhibition of Transforming Growth Factor Beta Signaling Enables
      the Endogenous Regenerative Potential of the Mammalian Calvarium.
AB  - Current approaches for the treatment of skeletal defects are suboptimal,
      principally because the ability of bone to repair and regenerate is poor.
      Although the promise of effective cellular therapies for skeletal repair is
      encouraging, these approaches are limited by the risks of infection, cellular
      contamination, and tumorigenicity. Development of a pharmacological approach
      would therefore help avoid some of these potential risks. This study identifies
      transforming growth factor beta (TGFbeta) signaling as a potential pathway for
      pharmacological modulation in vivo. We demonstrate that inhibition of TGFbeta
      signaling by the small molecule SB431542 potentiates calvarial skeletal repair
      through activation of bone morphogenetic protein (BMP) signaling on osteoblasts
      and dura mater cells participating in healing of calvarial defects. Cells respond
      to inhibition of TGFbeta signaling by producing higher levels of BMP2 that
      upregulates inhibitory Smad6 expression, thus providing a negative feedback loop
      to contain excessive BMP signaling. Importantly, study on human osteoblasts
      indicates that molecular mechanism(s) triggered by SB431542 are conserved.
      Collectively, these data provide insights into the use of small molecules to
      modulate key signaling pathways for repairing skeletal defects.

PMID- 27036932
TI  - Identification of male-biased microRNA-107 as a direct regulator for nuclear
      receptor subfamily 5 group A member 1 based on sexually dimorphic microRNA
      expression profiling from chicken embryonic gonads.
AB  - Several studies indicate that sexual dimorphic microRNAs (miRNAs) in chicken
      gonads are likely to have important roles in sexual development, but a more
      global understanding of the roles of miRNAs in sexual differentiation is still
      needed. To this end, we performed miRNA expression profiling in chicken gonads at
      embryonic day 5.5 (E5.5). Among the sex-biased miRNAs validated by qRT-PCR,
      twelve male-biased and six female-biased miRNAs were consistent with the
      sequencing results. Bioinformatics analysis revealed that some sex-biased miRNAs
      were potentially involved in gonadal development. Further functional analysis
      found that over-expression of miR-107 directly inhibited nuclear receptor
      subfamily 5 group A member 1 (NR5a1), and its downstream cytochrome P450 family
      19 subfamily A, polypeptide 1 (CYP19A1). However, anti-Mullerian hormone (AMH)
      was not directly or indirectly regulated by miR-107. Overall results indicate
      that miR-107 may specifically mediate avian ovary-development by post
      transcriptional regulation of NR5a1 and CYP19A1 in estrogen signaling pathways.

PMID- 27036933
TI  - The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of
      the ABCG2 transporter protein in human term placental explant cultures.
AB  - Many endogenous and xenobiotic compounds are substrates and regulators of human
      placental ABC transporters. ABCG2 is protecting fetus against foreign chemicals.
      Environmental xenoestrogens, like bisphenol A (BPA) and p-nonylphenol (p-NP),
      mimic natural estrogens and can affect hormonal systems. Effects of BPA, p-NP,
      DES (diethylstilbestrol) and estradiol (E2), on ABCG2 expression were studied
      using human first trimester and term placental explants. Role of estrogen
      receptors (ER) in the effects of chemicals was studied by ER antagonist. Term
      placenta expressed less ABCG2 protein. In term placentas BPA (p < 0.05), p-NP (p
      < 0.01) and E2 (p < 0.05) decreased the ABCG2 protein expression after 48 h
      exposure while after 24 h exposure, only E2 decreased the expression (p < 0.05).
      The chemicals did not affect ABCG2 in first trimester placentas. The ER
      antagonist affected differently the responses of chemicals. In conclusion,
      environmental xenoestrogens downregulate placental ABCG2 protein expression
      depending on gestational age.

PMID- 27036934
TI  - Strategies for Enhancing "Person Knowledge" in an Older People Care Setting.
AB  - This article presents findings from a study about compassionate care-the
      development of person knowledge in a medical ward caring for older people.
      Appreciative inquiry, an approach to research that focuses on discovering what
      works well and implementing strategies to help these aspects happen most of the
      time, was used. Staff, patients, and families participated in this study, which
      used a range of methods to generate data including interviews and observations.
      Immersion/crystallization was used to analyze these data using a reflexive and
      continuous approach to extracting and validating data. Findings uncovered that
      knowledge of the person and ways of promoting this were key dimensions of
      compassionate caring. The attributes of "caring conversations" emerged through
      the analysis process, which we suggest are crucial to developing person
      knowledge. The political and public focus on compassionate care makes it
      opportune to raise discussion around this form of knowledge in academic and
      practice debates.

PMID- 27036935
TI  - NYVAC vector modified by C7L viral gene insertion improves T cell immune
      responses and effectiveness against leishmaniasis.
AB  - The NYVAC poxvirus vector is used as vaccine candidate for HIV and other
      diseases, although there is only limited experimental information on its
      immunogenicity and effectiveness for use against human pathogens. Here we defined
      the selective advantage of NYVAC vectors in a mouse model by comparing the immune
      responses and protection induced by vectors that express the LACK (Leishmania
      activated C-kinase antigen), alone or with insertion of the viral host range gene
      C7L that allows the virus to replicate in human cells. Using DNA prime/virus
      boost protocols, we show that replication-competent NYVAC-LACK that expresses C7L
      (NYVAC-LACK-C7L) induced higher-magnitude polyfunctional CD8(+) and CD4(+)
      primary adaptive and effector memory T cell responses (IFNgamma, TNFalpha, IL-2,
      CD107a) to LACK antigen than non-replicating NYVAC-LACK. Compared to NYVAC-LACK,
      the NYVAC-LACK-C7L-induced CD8(+) T cell population also showed higher
      proliferation when stimulated with LACK antigen. After a challenge by
      subcutaneous Leishmania major metacyclic promastigotes, NYVAC-LACK-C7L-vaccinated
      mouse groups showed greater protection than the NYVAC-LACK-vaccinated group. Our
      results indicate that the type and potency of immune responses induced by LACK
      expressing NYVAC vectors is improved by insertion of the C7L gene, and that a
      replication-competent vector as a vaccine renders greater protection against a
      human pathogen than a non-replicating vector.

PMID- 27036936
TI  - Alcohol and drug involvement in motorcycle driver injuries in the city of Sao
      Paulo, Brazil: Analysis of crash culpability and other associated factors.
AB  - BACKGROUND: Earlier studies have already identified that a greater proportion of
      injured drivers are under the effects of illicit drugs than alcohol in Brazil,
      but the crash risk attributable to each substance is still unknown. METHODS:
      Injured motorcycle drivers who were involved in traffic accidents in the West
      Zone of the city of Sao Paulo were recruited for a cross-sectional study based on
      crash culpability analysis. Alcohol and drug positivity among drivers was
      evaluated according to their responsibility for the crash. Culpability ratios
      were generated based on the proportion of drivers who were deemed culpable in
      relation to those considered not culpable according to the use of drugs and
      alcohol. RESULTS: Of the 273 drivers recruited, 10.6% tested positive for
      alcohol. Among those who were also tested for drugs (n=232), 20.3% had consumed
      either alcohol and/or other drugs, 15.5% of whom were positive only for drugs
      other than alcohol, specifically cannabis and cocaine. Drivers who tested
      positive for alcohol were significantly less likely to possess a valid driver's
      license and to report driving professionally, whereas those who had consumed only
      drugs were more likely to drive professionally. The culpability ratio estimated
      for alcohol-positive drivers was three times higher than that for alcohol-free
      drivers, showing a superior ratio than drivers who had consumed only drugs other
      than alcohol, who presented a 1.7 times higher culpability ratio than drug-free
      drivers. CONCLUSION: Substance use was overrepresented among culpable motorcycle
      drivers, with alcohol showing a greater contribution to crash culpability than
      other drugs.

PMID- 27036938
TI  - Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non
      oxidative Ethanol Metabolism.
AB  - Fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of ethanol that
      accumulate in human tissues upon ethanol intake. Although FAEEs are considered as
      toxic metabolites causing cellular dysfunction and tissue damage, the enzymology
      of FAEE metabolism remains poorly understood. In this study, we used a
      biochemical screen in Saccharomyces cerevisiae to identify and characterize
      putative hydrolases involved in FAEE catabolism. We found that Yju3p, the
      functional orthologue of mammalian monoacylglycerol lipase (MGL), contributes
      >90% of cellular FAEE hydrolase activity, and its loss leads to the accumulation
      of FAEE. Heterologous expression of mammalian MGL in yju3Delta mutants restored
      cellular FAEE hydrolase activity and FAEE catabolism. Moreover, overexpression or
      pharmacological inhibition of MGL in mouse AML-12 hepatocytes decreased or
      increased FAEE levels, respectively. FAEEs were transiently incorporated into
      lipid droplets (LDs) and both Yju3p and MGL co-localized with these organelles.
      We conclude that the storage of FAEE in inert LDs and their mobilization by LD
      resident FAEE hydrolases facilitate a controlled metabolism of these potentially
      toxic lipid metabolites.

PMID- 27036939
TI  - i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor
      CXCR4.
AB  - CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic
      target for a range of clinical conditions, including stem cell mobilization,
      cancer prognosis and treatment, fibrosis therapy, and HIV infection. We report
      here the development of a fully human single-domain antibody-like scaffold termed
      an "i-body," the engineering of which produces an i-body library possessing a
      long complementarity determining region binding loop, and the isolation and
      characterization of a panel of i-bodies with activity against human CXCR4. The
      CXCR4-specific i-bodies show antagonistic activity in a range of in vitro and in
      vivo assays, including inhibition of HIV infection, cell migration, and leukocyte
      recruitment but, importantly, not the mobilization of hematopoietic stem cells.
      Epitope mapping of the three CXCR4 i-bodies AM3-114, AM4-272, and AM3-523
      revealed binding deep in the binding pocket of the receptor.

PMID- 27036940
TI  - Trypanosoma brucei Methylthioadenosine Phosphorylase Protects the Parasite from
      the Antitrypanosomal Effect of Deoxyadenosine: IMPLICATIONS FOR THE PHARMACOLOGY
      OF ADENOSINE ANTIMETABOLITES.
AB  - Trypanosoma brucei causes African sleeping sickness for which no vaccine exists
      and available treatments are of limited use due to their high toxicity or lack of
      efficacy. T. brucei cultivated in the presence of deoxyadenosine accumulates high
      levels of dATP in an adenosine kinase-dependent process and dies within a few
      hours. Here we show that T. brucei treated with 1 mm deoxyadenosine accumulates
      higher dATP levels than mammalian cells but that this effect diminishes quickly
      as the concentration of the deoxynucleoside decreases. Radioactive tracer studies
      showed that the parasites are partially protected against lower concentrations of
      deoxyadenosine by the ability to cleave it and use the adenine for ATP synthesis.
      T. brucei methylthioadenosine phosphorylase (TbMTAP) was found to be responsible
      for the cleavage as indicated by the phosphate dependence of deoxyadenosine
      cleavage in T. brucei cell extracts and increased deoxyadenosine sensitivity in
      TbMTAP knockdown cells. Recombinant TbMTAP exhibited higher turnover number
      (kcat) and Km values for deoxyadenosine than for the regular substrate,
      methylthioadenosine. One of the reaction products, adenine, inhibited the enzyme,
      which might explain why TbMTAP-mediated protection is less efficient at higher
      deoxyadenosine concentrations. Consequently, T. brucei grown in the presence of
      adenine demonstrated increased sensitivity to deoxyadenosine. For
      deoxyadenosine/adenosine analogues to remain intact and be active against the
      parasite, they need to either be resistant to TbMTAP-mediated cleavage, which is
      the case with the three known antitrypanosomal agents adenine arabinoside,
      tubercidin, and cordycepin, or they need to be combined with TbMTAP inhibitors.

PMID- 27036941
TI  - Entry of Bluetongue Virus Capsid Requires the Late Endosome-specific Lipid
      Lysobisphosphatidic Acid.
AB  - The entry of viruses into host cells is one of the key processes of infection.
      The mechanisms of cellular entry for enveloped virus have been well studied. The
      fusion proteins as well as the facilitating cellular lipid factors involved in
      the viral fusion entry process have been well characterized. The process of non
      enveloped virus cell entry, in comparison, remains poorly defined, particularly
      for large complex capsid viruses of the family Reoviridae, which comprises a
      range of mammalian pathogens. These viruses enter cells without the aid of a
      limiting membrane and thus cannot fuse with host cell membranes to enter cells.
      Instead, these viruses are believed to penetrate membranes of the host cell
      during endocytosis. However, the molecular mechanism of this process is largely
      undefined. Here we show, utilizing an in vitro liposome penetration assay and
      cell biology, that bluetongue virus (BTV), an archetypal member of the
      Reoviridae, utilizes the late endosome-specific lipid lysobisphosphatidic acid
      for productive membrane penetration and viral entry. Further, we provide
      preliminary evidence that lipid lysobisphosphatidic acid facilitates pore
      expansion during membrane penetration, suggesting a mechanism for lipid factor
      requirement of BTV. This finding indicates that despite the lack of a membrane
      envelope, the entry process of BTV is similar in specific lipid requirements to
      enveloped viruses that enter cells through the late endosome. These results are
      the first, to our knowledge, to demonstrate that a large non-enveloped virus of
      the Reoviridae has specific lipid requirements for membrane penetration and host
      cell entry.

PMID- 27036942
TI  - Role of Glyoxylate Shunt in Oxidative Stress Response.
AB  - The glyoxylate shunt (GS) is a two-step metabolic pathway (isocitrate lyase,
      aceA; and malate synthase, glcB) that serves as an alternative to the
      tricarboxylic acid cycle. The GS bypasses the carbon dioxide-producing steps of
      the tricarboxylic acid cycle and is essential for acetate and fatty acid
      metabolism in bacteria. GS can be up-regulated under conditions of oxidative
      stress, antibiotic stress, and host infection, which implies that it plays
      important but poorly explored roles in stress defense and pathogenesis. In many
      bacterial species, including Pseudomonas aeruginosa, aceA and glcB are not in an
      operon, unlike in Escherichia coli In P. aeruginosa, we explored relationships
      between GS genes and growth, transcription profiles, and biofilm formation.
      Contrary to our expectations, deletion of aceA in P. aeruginosa improved cell
      growth under conditions of oxidative and antibiotic stress. Transcriptome data
      suggested that aceA mutants underwent a metabolic shift toward aerobic
      denitrification; this was supported by additional evidence, including up
      regulation of denitrification-related genes, decreased oxygen consumption without
      lowering ATP yield, increased production of denitrification intermediates (NO and
      N2O), and increased cyanide resistance. The aceA mutants also produced a thicker
      exopolysaccharide layer; that is, a phenotype consistent with aerobic
      denitrification. A bioinformatic survey across known bacterial genomes showed
      that only microorganisms capable of aerobic metabolism possess the glyoxylate
      shunt. This trend is consistent with the hypothesis that the GS plays a
      previously unrecognized role in allowing bacteria to tolerate oxidative stress.

PMID- 27036943
TI  - Structural Divergence of the Group I Intron Binding Surface in Fungal
      Mitochondrial Tyrosyl-tRNA Synthetases That Function in RNA Splicing.
AB  - The mitochondrial tyrosyl-tRNA synthetases (mtTyrRSs) of Pezizomycotina fungi, a
      subphylum that includes many pathogenic species, are bifunctional proteins that
      both charge mitochondrial tRNA(Tyr) and act as splicing cofactors for
      autocatalytic group I introns. Previous studies showed that one of these
      proteins, Neurospora crassa CYT-18, binds group I introns by using both its N
      terminal catalytic and C-terminal anticodon binding domains and that the
      catalytic domain uses a newly evolved group I intron binding surface that
      includes an N-terminal extension and two small insertions (insertions 1 and 2)
      with distinctive features not found in non-splicing mtTyrRSs. To explore how this
      RNA binding surface diverged to accommodate different group I introns in other
      Pezizomycotina fungi, we determined x-ray crystal structures of C-terminally
      truncated Aspergillus nidulans and Coccidioides posadasii mtTyrRSs. Comparisons
      with previous N. crassa CYT-18 structures and a structural model of the
      Aspergillus fumigatus mtTyrRS showed that the overall topology of the group I
      intron binding surface is conserved but with variations in key intron binding
      regions, particularly the Pezizomycotina-specific insertions. These insertions,
      which arose by expansion of flexible termini or internal loops, show greater
      variation in structure and amino acids potentially involved in group I intron
      binding than do neighboring protein core regions, which also function in intron
      binding but may be more constrained to preserve mtTyrRS activity. Our results
      suggest a structural basis for the intron specificity of different Pezizomycotina
      mtTyrRSs, highlight flexible terminal and loop regions as major sites for enzyme
      diversification, and identify targets for therapeutic intervention by disrupting
      an essential RNA-protein interaction in pathogenic fungi.

PMID- 27036944
TI  - A logistic model to predict early pregnancy loss following in vitro fertilization
      based on 2601 infertility patients.
AB  - BACKGROUND: According to previous studies, even after embryonic cardiac activity
      is detected, the pregnancy loss rate remains 3-4 %. The objectives of this study
      were to investigate the differences in ultrasound parameters between a
      miscarriage group and an ongoing pregnancy group during the 1(st) trimester and
      to build a logistic model to predict early pregnancy loss (EPL) after the
      appearance of embryonic cardiac activity in patients who have undergone in vitro
      fertilization embryo transfer (IVF-ET) treatment. METHOD: A total of 2601
      patients with early singleton pregnancies with embryonic cardiac activity were
      retrospectively analyzed after IVF from January 2010 to June 2011. Transvaginal
      sonography (TVS) was performed at 6 to 10 weeks of gestational age (GA). The mean
      gestational sac diameter (MSD), crown-rump length (CRL), fetal heart rate (FHR),
      and yolk sac diameter (YSD) were measured by TVS. RESULTS: A total of 2400
      patients had an ongoing pregnancy and an additional 201 (7.7 %) patients
      miscarried during the first trimester after fetal cardiac activity had been
      established. The maternal age (MA) and infertility duration were much greater,
      and the MSD, CRL, and FHR were much lower in the miscarriage group than in the
      ongoing pregnancy group after IVF (P < 0.05). The prediction model utilized the
      following equation: the possibility of EPL = exp(z)/(1 + exp(z)), where z = 
      21.456 + (0.114 * MA) + (4.305 * * GA) - (0.043 * MSD) - (0.359 * CRL) - (0.091 *
      FHR) + 2.243 (fluid collection present around the gestational sac (GS)) + 2.519
      (when YSD < 3) or - 0.347 (when YSD > 5.5). CONCLUSION: The MA, MSD, CRL, YSD,
      FHR, infertility duration, and fluid collection around the GS were each
      correlated with EPL after IVF in infertile patients. A logistic model is a useful
      tool for predicting EPL after the appearance of embryonic cardiac activity (area
      under the curve [AUC] = 0.909).

PMID- 27036945
TI  - Anxiety and associated factors among prisoners in North West of Amhara Regional
      State, Ethiopia.
AB  - BACKGROUND: Mental illnesses are more common among the prison population than the
      general public. However, little attention is given to mental health service in
      low and middle income countries in general. The problem is more so for prisoners
      where the overall health care is poor. Therefore, the aim of this study was to
      assess the prevalence of anxiety and the associated factors among prisoners of
      North West Amhara, Ethiopia. METHODS: Institutional based cross-sectional study
      was employed from February to March 2015 by taking a sample of 700 prisoners.
      Simple random sampling method was employed to select three prisons out of 10
      prisons found in the North West Amhara region. Generalized Anxiety Disorder 7
      item (GAD-7) scale was used to assess prisoners' anxiety status. The receiver-
      operator characteristic (ROC) curve was used to determine the cutoff point with
      high sensitivity and specificity. Structured and pretested interviewer
      administered questionnaire was used for data collection. Data were checked, coded
      and entered into Epi Info version 7 and analyzed using R version 3.2.0.
      Bivariable and multivariable logistic regression analyses were carried out to
      identify factors associated with anxiety. Odds ratio with its 95 % confidence
      interval was used as a measure of association. Akaike's Information's Criterion
      (AIC) was used to check model fitness. RESULTS: A total of 649 prisoners were
      included in the analysis making the response rate 92.5 %. The prevalence of
      Anxiety was found to be 36.1 % (95 % CI: 32.7, 39.9). The odds of Anxiety was
      2.49(95 % CI: 1.38, 4.55) times higher among prisoners who used to be unhappy in
      their life before imprisonment. Moreover, smokers were 2.6 (AOR = 2.6, 95 % CI:
      1.08, 6.6) times more likely to have anxiety compared with non smokers. However,
      the odds of the odds of anxiety was 89% lower among Debre-Tabor prisoners (AOR =
      0.11, 95 % CI: 0.06, 0.20) and 57 % lower among Gondar prisoners (AOR = 0.43, 95
      % CI: 0.28, 0.67). CONCLUSION: The prevalence of anxiety is found to be very high
      among prisoners in North West Ethiopia. Anxiety was associated with current
      smoking and having had a dissatisfying life. Screening prisoners for common
      mental disorders and integrated health care is necessary.

PMID- 27036946
TI  - The beneficial role of memory reactivation for language learning during sleep: A
      review.
AB  - Sleep is essential for diverse aspects of language learning. According to a
      prominent concept these beneficial effects of sleep rely on spontaneous
      reactivation processes. A series of recent studies demonstrated that inducing
      such reactivation processes by re-exposure to memory cues during sleep enhances
      foreign vocabulary learning. Building upon these findings, the present article
      reviews recent models and empirical findings concerning the beneficial effects of
      sleep on language learning. Consequently, the memory function of sleep, its
      neural underpinnings and the role of the sleeping brain in language learning will
      be summarized. Finally, we will propose a working model concerning the
      oscillatory requirements for successful reactivation processes and future
      research questions to advance our understanding of the role of sleep on language
      learning and memory processes in general.

PMID- 27036947
TI  - Familial tetrasomy 4q35.2 associated with congenital diaphragmatic hernia and
      unilateral renal agenesis: a case report.
AB  - BACKGROUND: Previous reports of chromosomal aberrations in different forms of
      congenital diaphragmatic hernia have been described as comprising aneuploidies
      (for example, trisomy 21), microdeletions, and duplications (for example,
      monosomy 15q24, 22q11.2). CASE PRESENTATION: We describe the first association of
      a de novo partial tetrasomy 4q35.2 in a father with left-sided, isolated renal
      agenesis and left-sided, isolated congenital diaphragmatic hernia in his son, who
      inherited the chromosomal aberration from his father. CONCLUSIONS: Given that the
      aberration occurred de novo in the father and was transmitted to his son, with
      both presenting with unilateral left-sided developmental field defects, we
      suggest a gene dosage effect of the tetrasomic region to be involved in the
      phenotype of our two patients. Furthermore, we suggest performing a genetic
      workup in multiplex families with congenital malformations.

PMID- 27036948
TI  - Women with endometriosis show higher risk for heart disease.

PMID- 27036950
TI  - Origins and Progression of Adolescent Endometriosis.
AB  - Accumulating evidence indicates that adolescent endometriosis is common and often
      severe. Here we explore the possibility that seeding of naive endometrial
      progenitor cells into the pelvic cavity early in life, that is, at the time of
      neonatal uterine bleeding or soon after the menarche, results in more florid and
      progressive disease, characterized by highly angiogenic implants, recurrent
      ectopic bleeding, and endometrioma formation. We discuss the potential
      intergenerational risk factors associated with early-onset endometriosis and
      explore the molecular drivers of disease progression. Taken together, the
      available data suggest that an increased focus on early-life events may help to
      identify young women at risk of severe, progressive endometriosis.

PMID- 27036949
TI  - Upregulation of calpain activity precedes tau phosphorylation and loss of
      synaptic proteins in Alzheimer's disease brain.
AB  - Alterations in calcium homeostasis are widely reported to contribute to synaptic
      degeneration and neuronal loss in Alzheimer's disease. Elevated cytosolic calcium
      concentrations lead to activation of the calcium-sensitive cysteine protease,
      calpain, which has a number of substrates known to be abnormally regulated in
      disease. Analysis of human brain has shown that calpain activity is elevated in
      AD compared to controls, and that calpain-mediated proteolysis regulates the
      activity of important disease-associated proteins including the tau kinases
      cyclin-dependent kinase 5 and glycogen kinase synthase-3. Here, we sought to
      investigate the likely temporal association between these changes during the
      development of sporadic AD using Braak staged post-mortem brain. Quantification
      of protein amounts in these tissues showed increased activity of calpain-1 from
      Braak stage III onwards in comparison to controls, extending previous findings
      that calpain-1 is upregulated at end-stage disease, and suggesting that
      activation of calcium-sensitive signalling pathways are sustained from early
      stages of disease development. Increases in calpain-1 activity were associated
      with elevated activity of the endogenous calpain inhibitor, calpastatin, itself a
      known calpain substrate. Activation of the tau kinases, glycogen-kinase synthase
      3 and cyclin-dependent kinase 5 were also found to occur in Braak stage II-III
      brain, and these preceded global elevations in tau phosphorylation and the loss
      of post-synaptic markers. In addition, we identified transient increases in total
      amyloid precursor protein and pre-synaptic markers in Braak stage II-III brain,
      that were lost by end stage Alzheimer's disease, that may be indicative of
      endogenous compensatory responses to the initial stages of neurodegeneration.
      These findings provide insight into the molecular events that underpin the
      progression of Alzheimer's disease, and further highlight the rationale for
      investigating novel treatment strategies that are based on preventing abnormal
      calcium homeostasis or blocking increases in the activity of calpain or important
      calpain substrates.

PMID- 27036952
TI  - Multi-morbidity, frailty and self-care: important considerations in treatment
      with anticoagulation drugs. Outcomes of the AFASTER study.
AB  - BACKGROUND: Chronic heart failure (CHF) and atrial fibrillation (AF) are complex
      cardiogeriatric syndromes mediated by physical, psychological and social factors.
      Thromboprophylaxis is an important part of avoiding adverse events in these
      syndromes, particularly stroke. PURPOSE: This study sought to describe the
      clinical characteristics of a cohort of patients admitted to hospital with CHF
      and concomitant AF and to document the rate and type of thromboprophylaxis. We
      examined the practice patterns of the prescription of treatment and determined
      the predictors of adverse events. METHODS: Prospective consecutive participants
      with CHF and concomitant AF were enrolled during the period April to October
      2013. Outcomes were assessed at 12 months, including all-cause readmission to
      hospital and mortality, stroke or transient ischaemic attack, and bleeding.
      RESULTS: All-cause readmission to hospital was frequent (68%) and the 12-month
      all-cause mortality was high (29%). The prescription of anticoagulant drugs at
      discharge was statistically significantly associated with a lower mortality at 12
      months (23 vs. 40%; p=0.037; hazards ratio 0.506; 95% confidence interval 0.267
      0.956), but was not associated with lower rates of readmission to hospital among
      patients with CHF and AF. Sixty-six per cent of participants were prescribed
      anticoagulant drugs on discharge from hospital. Self-reported self-care behaviour
      and 'not for cardiopulmonary resuscitation' were associated with not receiving
      anticoagulant drugs at discharge. Although statistical significance was not
      achieved, those patients who were assessed as frail or having greater comorbidity
      were less likely to receive anticoagulant drugs at discharge. CONCLUSION: This
      study highlights multi-morbidity, frailty and self-care to be important
      considerations in thromboprophylaxis. Shared decision-making with patients and
      caregivers offers the potential to improve treatment knowledge, adherence and
      outcomes in this group of patients with complex care needs.

PMID- 27036953
TI  - Leg wound infection after coronary artery bypass grafting: A natural experiment
      comparing use and non-use of a compression stocking.
AB  - BACKGROUND: Harvest site infections after coronary artery bypass grafting (CABG)
      are a known complication which represent a serious problem for patients and an
      increased cost of health care. There is a discrepancy in routine care regarding
      use of a graduated compression stocking on the leg with the saphenous vein
      harvest site. Some wards apply a compression stocking postoperatively to all in
      hospital patients, others do not. The deep vein thrombosis prevention effect of
      compression stockings is well documented, but there are no studies of their
      possible preventive effect on harvest site infections. AIM: Our purpose was to
      examine whether the use of a graduated compression stocking for 4-6 weeks after
      CABG reduced the incidence of surgical wound infection at harvest sites. METHODS:
      Data on 377 consecutive CABG patients (September 2011-December 2012) were
      collected from the hospital's patient registry and Surveillance System for
      Surgical Site Infections. Logistic regression was used to determine the odds of
      surgical site infection in patients at two surgical wards adhering to opposite
      practices regarding the use of compression stocking (stocking group n=296, no
      stocking group n=155). RESULTS: No significant relationship was found between
      post-operative infection rate and compression stocking routine. CONCLUSION: In
      this 'natural experiment' no evidence was found that the use of a graduated
      compression stocking reduced the incidence of harvest site surgical wound
      infection. As the treatment of most Norwegian CABG patients involves the use of a
      graft leg compression stocking, a randomised controlled trial (RCT) is called for
      to decide which treatment is better.

PMID- 27036951
TI  - Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene
      MSH2 in Human Uterine Fibroids.
AB  - Uterine fibroids (UFs) are benign smooth muscle neoplasms affecting up to 70% of
      reproductive age women. Treatment of symptomatic UFs places a significant
      economic burden on the US health-care system. Several specific genetic
      abnormalities have been described as etiologic factors of UFs, suggesting that a
      low DNA damage repair capacity may be involved in the formation of UF. In this
      study, we used human fibroid and adjacent myometrial tissues, as well as an in
      vitro cell culture model, to evaluate the expression of MutS homolog 2 (MSH2),
      which encodes a protein belongs to the mismatch repair system. In addition, we
      deciphered the mechanism by which polycomb repressive complex 2 protein, EZH2,
      deregulates MSH2 in UFs. The RNA expression analysis demonstrated the
      deregulation of MSH2 expression in UF tissues in comparison to its adjacent
      myometrium. Notably, protein levels of MSH2 were upregulated in 90% of fibroid
      tissues (9 of 10) as compared to matched adjacent myometrial tissues. Human
      fibroid primary cells treated with 3-deazaneplanocin A (DZNep), chemical
      inhibitor of EZH2, exhibited a significant increase in MSH2 expression (P < .05).
      Overexpression of EZH2 using an adenoviral vector approach significantly
      downregulated the expression of MSH2 (P < .05). Chromatin immunoprecipitation
      assay demonstrated that enrichment of H3K27me3 in promoter regions of MSH2 was
      significantly decreased in DZNep-treated fibroid cells as compared to vehicle
      control. These data suggest that EZH2-H3K27me3 regulatory mechanism dynamically
      changes the expression levels of DNA mismatch repair gene MSH2, through
      epigenetic mark H3K27me3. MSH2 may be considered as a marker for early detection
      of UFs.

PMID- 27036954
TI  - The association between atrial fibrillation and cognitive function in patients
      with heart failure.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with cognitive impairment in
      heart failure (HF). AIMS: The purpose of this study was to examine whether AF
      independently predicted cognitive function in HF patients after controlling for
      more demographic, medical and psychological characteristics, and whether the
      timing of AF onset in relation to HF diagnosis independently contributed to
      cognitive function in HF patients with AF. METHODS: A total of 188 hospitalized
      HF patients (62.8% male, age 66.3+/-10.6 years) completed cognitive function
      assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along
      with other medical characteristics, was ascertained through a review of
      participants' medical charts. The timing of AF onset in relation to HF diagnosis
      was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF
      developing after HF diagnosis (i.e. incident AF). RESULTS: Altogether 72
      participants had a positive diagnostic history of AF. Specifically, 41 had prior
      AF, and 31 developed AF subsequently. In HF patients, AF was associated with
      poorer performance on cognitive function after controlling for more confounders
      (beta=-0.112, DeltaR2=0.010, p=0.046). Among HF patients with AF, incident AF
      independently predicted poorer cognitive function (beta=-0.238, DeltaR2=0.027,
      p=0.047). CONCLUSION: AF independently contributes to cognitive function in HF
      patients after adjusting for more confounding variables. The timing of AF onset
      in relation to HF diagnosis independently predicts cognitive function in HF
      patients with AF. Prospective studies are needed to elucidate possible mechanisms
      for the association between AF and cognitive function in HF populations.

PMID- 27036955
TI  - Changes in self-reported health and quality of life in octogenarian patients one
      month after transcatheter aortic valve implantation.
AB  - BACKGROUND: In addition to favourable results regarding mortality and morbidity
      it is important to identify the impact transcatheter aortic valve implantation
      (TAVI) has on patients' quality of life. AIMS: The aims were: (i) to describe
      clinical characteristics, self-reported health and quality of life in
      octogenarians before TAVI intervention; (ii) to determine changes in self
      reported health and quality of life one month after TAVI; and (iii) to establish
      the clinical importance of the findings. METHODS: A prospective cohort study was
      conducted on consecutively enrolled octogenarians with severe aortic stenosis
      undergoing TAVI ( N = 65). Self-reported health and quality of life were recorded
      at baseline and one month later using two global questions from the World Health
      Organization Quality of Life Instrument Abbreviated (WHOQOL-BREF), the generic
      Short Form Health 12 and the disease-specific Minnesota Living with Heart Failure
      Questionnaire. RESULTS: One month after TAVI, WHOQOL-BREF showed that self
      reported health improved moderately ( p < 0.001), while quality of life improved
      slightly, but not statistically significantly ( p = 0.06). There were changes in
      all Short Form Health 12 domains, except social functioning and role emotional.
      The estimated changes were 3.6 to 5.8 with large confidence intervals. The
      Physical Component Summary increased statistically significantly from baseline to
      30 days (30.6-34.7; p = 0.02), but the Mental Component Summary did not (46.9
      50.0; p = 0.13). CONCLUSION: Despite being an advanced treatment performed in a
      high risk population, TAVI in octogenarians improves short-term self-reported
      global health and generic physical health and quality of life. These patient
      reported outcomes have importance, particularly in this age group.

PMID- 27036956
TI  - Validation of a Spanish translation of the Gratitude Questionnaire (GQ-6) with a
      Chilean sample of adults and high schoolers.
AB  - BACKGROUND: Recent studies have associated positive emotions with several
      variables such as learning, coping strategies or assertive behaviour. The concept
      of gratitude has been specifically defined as a tendency to recognise and respond
      to people or situations with grateful emotion. Unfortunately in Latin America, no
      validated measures of gratitude on different populations are available. The aim
      of this study was to analyse the psychometric properties of the Gratitude
      Questionnaire (GQ-6) in two Chilean samples. METHODS: Two studies were conducted:
      the first with 668 high school adolescents (390 women and 278 men, with ages
      ranging between 12 and 20, and a mean age 15.54 +/- 1.22) and the second with 331
      adults (231 women and 100 men, with an average age of 37.59 +/- 12.6). An
      analysis of the psychometric properties of the GQ-6 scale to determine the
      validity and reliability of the instrument in Chilean adolescents and adults was
      performed. Bivariate correlations, multiple regression analyses, exploratory
      factor analysis (EFA) and Monte Carlo simulations were carried out. Finally, a
      confirmatory factor analysis (CFA) was performed. RESULTS: A single-factor
      solution was found in both studies, a 5 item version for the adolescents and 6
      items for adults. This factorial solution was invariant across genders.
      Reliability of the GQ was adequate in both samples (using Cronbach's alpha
      coefficient). In addition convergent and discriminate validity were assessed.
      Additionally, a negative correlation between the GQ-5 and depression in
      adolescents and a positive correlation between the GQ-6 and happiness in adults
      was found. CONCLUSIONS: The GQ is a suitable measure for evaluating a person's
      disposition toward gratitude in Chilean adolescents and adults. This instrument
      may contribute to the advancement of the study of positive emotions in Latin
      America.

PMID- 27036960
TI  - Association of breakfast consumption with body mass index and prevalence of
      overweight/obesity in a nationally-representative survey of Canadian adults.
AB  - BACKGROUND: This study examined the association of breakfast consumption, and the
      type of breakfast consumed, with body mass index (BMI; kg/m(2)) and prevalence
      rates and odds ratios (OR) of overweight/obesity among Canadian adults. These
      associations were examined by age group and sex. METHODS: We used data from non
      pregnant, non-lactating participants aged >= 18 years (n = 12,377) in the
      Canadian Community Health Survey Cycle 2.2, a population-based, nationally
      representative, cross-sectional study. Height and weight were measured, and BMI
      was calculated. Breakfast consumption was self-reported during a standardized 24
      h recall; individuals were classified as breakfast non-consumers, consumers of
      breakfasts that included ready-to-eat cereal (RTEC) or as other breakfast
      consumers. Mean BMI and prevalence and OR of overweight/obesity (BMI >= 25) were
      compared among breakfast groups, with adjustment for sociodemographic variables
      (including age, sex, race, marital status, food security, language spoken at
      home, physical activity category, smoking, education level and supplement use).
      RESULTS: For the entire sample, mean BMI was significantly lower among RTEC
      breakfast consumers than other breakfast consumers (mean +/- SE 26.5 +/- 0.2 vs.
      27.1 +/- 0.1 kg/m(2)), but neither group differed significantly from breakfast
      non-consumers (27.1 +/- 0.3 kg/m(2)). Similar results were seen in women only,
      but BMI of men did not differ by breakfast category. Overweight/obesity
      prevalence and OR did not differ among breakfast groups for the entire sample or
      for all men and women separately. When examined by sex and age group, differences
      were inconsistent, but tended to be more apparent in women than men. CONCLUSION:
      Among Canadian adults, breakfast consumption was not consistently associated with
      differences in BMI or overweight/obesity prevalence.

PMID- 27036961
TI  - Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their
      application to combat the infection caused by Mala s1 a novel allergen.
AB  - BACKGROUND: Malassezia commensal yeasts along with multitude of antigens have
      been found to be associated with various skin disorders including Pityriasis
      versicolor (PV). Amongst them Mala s1, a 37 kDa protein has been proved to be a
      major allergen reacting with a large panel of sera. However, there exists no
      therapeutic alternative to combat such problems in form of plant based natural
      compounds. The purpose of this study is in the first place, to determine the anti
      Malassezia activity of Nyctanthes arbor-tristis L. (NAT) ethanolic leaf extract
      through turbidimetric growth curves, disruption of plasma membrane and secondly,
      it aims to present in silico validation of its active constituents over Mala s1a
      novel allergen. METHODS: The antifungal susceptibility 50 % ethanolic extract of
      NAT was determined by broth microdilution method according to CLSI guidelines.
      Further MICs and IC50 were determined spectrophotometrically using the software
      SoftMax(r) Pro-5 (Molecular Devices, USA). Active constituents mediated
      disruption of plasma membrane was studied through flowcytometry by
      permeabilization of fluorescent dye Propidium Iodide (PI). Antioxidant activity
      of the extract was determined using the DPPH stable radical. Molecular validation
      of fungal DNA from the extract was observed using PCR amplification. In silico
      analysis of its active constituents over Mala s1 was performed using HEX software
      and visualized through Pymol. RESULTS: The anti-Malassezia potential of NAT leaf
      extracts reflected moderate MIC 1.05 MUg/MUl against M. globosa, while least
      effective against M. restricta with MIC 1.47 MUg/MUl. A linear correlation
      coefficient R (2) = 0.866 was obtained in case of M. globosa while minimum was
      observed in M. restricta with R (2) = 0.732. The flow cytometric data reveal ~ 75
      % cell death when treated with active constituents beta-Sitosterol and
      Calceolarioside A. The docking confirmations and the interaction energies between
      Mala s1 and the active constituents (beta-Sitosterol and Calceolarioside A) from
      extracts showed an effective binding which suggests Mala s1 as efficient allergen
      for site specific targeting. CONCLUSIONS: This study revealed that Nyctanthes
      arbor-tristis L. (NAT) extracts possess high anti-Malassezia potential which is
      driven mainly by disruption of plasma membrane. Also in silico validation and
      molecular modeling studies establishes Mala s1 as a novel allergen that could be
      a potential target in disease treatment. Our results would also provide a
      foundation for the development of new therapeutic approach using NAT extract as
      lead compound with high antioxidant property as an added trait for skin care.

PMID- 27036962
TI  - Is there continued evidence for an association between abacavir usage and
      myocardial infarction risk in individuals with HIV? A cohort collaboration.
AB  - BACKGROUND: In March 2008, the D:A:D study published results demonstrating an
      increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We
      describe changes to the use of ABC since this date, and investigate changes to
      the association between ABC and MI with subsequent follow-up. METHODS: A total of
      49,717 D:A:D participants were followed from study entry until the first of an
      MI, death, 1 February 2013 or 6 months after last visit. Associations between a
      person's 10-year cardiovascular disease (CVD) risk and the likelihood of
      initiating or discontinuing ABC were assessed using multivariable
      logistic/Poisson regression. Poisson regression was used to assess the
      association between current ABC use and MI risk, adjusting for potential
      confounders, and a test of interaction was performed to assess whether the
      association had changed in the post-March 2008 period. RESULTS: Use of ABC
      increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at
      18-19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest
      in those at moderate and high CVD risk. Post-March 2008, those on ABC at
      moderate/high CVD risk were more likely to discontinue ABC than those at
      low/unknown CVD risk, regardless of viral load (<=1,000 copies/ml: relative rate
      1.49 [95 % confidence interval 1.34-1.65]; >1,000 copies/ml: 1.23 [1.02-1.48]);
      no such associations were seen pre-March 2008. There was some evidence that
      antiretroviral therapy (ART)-naive persons at moderate/high CVD risk post-March
      2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds
      ratio 0.74 [0.48-1.13]). By 1 February 2013, 941 MI events had occurred in
      367,559 person-years. Current ABC use was associated with a 98 % increase in MI
      rate (RR 1.98 [1.72-2.29]) with no difference in the pre- (1.97 [1.68-2.33]) or
      post- (1.97 [1.43-2.72]) March 2008 periods (interaction P = 0.74). CONCLUSIONS:
      Despite a reduction in the channelling of ABC for patients at higher CVD risk
      since 2008, we continue to observe an association between ABC use and MI risk.
      Whilst confounding cannot be fully ruled out, this further diminishes channelling
      bias as an explanation for our findings.

PMID- 27036963
TI  - On the use of propensity scores in case of rare exposure.
AB  - BACKGROUND: Observational post-marketing assessment studies often involve
      evaluating the effect of a rare treatment on a time-to-event outcome, through the
      estimation of a marginal hazard ratio. Propensity score (PS) methods are the most
      used methods to estimate marginal effect of an exposure in observational studies.
      However there is paucity of data concerning their performance in a context of low
      prevalence of exposure. METHODS: We conducted an extensive series of Monte Carlo
      simulations to examine the performance of the two preferred PS methods, known as
      PS-matching and PS-weighting to estimate marginal hazard ratios, through various
      scenarios. RESULTS: We found that both PS-weighting and PS-matching could be
      biased when estimating the marginal effect of rare exposure. The less biased
      results were obtained with estimators of average treatment effect in the treated
      population (ATT), in comparison with estimators of average treatment effect in
      the overall population (ATE). Among ATT estimators, PS-weighting using ATT
      weights outperformed PS-matching. These results are illustrated using a real
      observational study. CONCLUSIONS: When clinical objectives are focused on the
      treated population, applied researchers are encouraged to estimate ATT with PS
      weighting for studying the relative effect of a rare treatment on time-to-event
      outcomes.

PMID- 27036964
TI  - Proton irradiation induces persistent and tissue-specific DNA methylation changes
      in the left ventricle and hippocampus.
AB  - BACKGROUND: Proton irradiation poses a potential hazard to astronauts during and
      following a mission, with post-mitotic cells at most risk because they cannot
      dilute resultant epigenetic changes via cell division. Persistent epigenetic
      changes that result from environmental exposures include gains or losses of DNA
      methylation of cytosine, which can impact gene expression. In the present study,
      we compared the long-term epigenetic effects of whole body proton irradiation in
      the mouse hippocampus and left ventricle. We used an unbiased genome-wide DNA
      methylation study, involving ChIP-seq with antibodies to 5-methylcytosine (5mC)
      and 5-hydroxymethylcytosine (5hmC) to identify DNA regions in which methylation
      levels have changed 22 weeks after a single exposure to proton irradiation. We
      used DIP-Seq to profile changes in genome-wide DNA methylation and
      hydroxymethylation following proton irradiation. In addition, we used published
      RNAseq data to assess whether differentially methylated regions were linked to
      changes in gene expression. RESULTS: The DNA methylation data showed tissue
      dependent effects of proton irradiation and revealed significant major pathway
      changes in response to irradiation that are related to known pathophysiologic
      processes. Many regions affected in the ventricle mapped to genes involved in
      cardiovascular function pathways, whereas many regions affected in the
      hippocampus mapped to genes involved in neuronal functions. In the ventricle,
      increases in 5hmC were associated with decreases in 5mC. We also observed spatial
      overlap for regions where both epigenetic marks decreased in the ventricle. In
      hippocampus, increases in 5hmC were most significantly correlated (spatially)
      with regions that had increased 5mC, suggesting that deposition of hippocampal
      5mC and 5hmC may be mechanistically coupled. CONCLUSIONS: The results demonstrate
      long-term changes in DNA methylation patterns following a single proton
      irradiation, that these changes are tissue specific, and that they map to
      pathways consistent with tissue specific responses to proton irradiation.
      Further, the results suggest novel relationships between changes in 5mC and 5hmC.

PMID- 27036965
TI  - Role of TET enzymes in DNA methylation, development, and cancer.
AB  - The pattern of DNA methylation at cytosine bases in the genome is tightly linked
      to gene expression, and DNA methylation abnormalities are often observed in
      diseases. The ten eleven translocation (TET) enzymes oxidize 5-methylcytosines
      (5mCs) and promote locus-specific reversal of DNA methylation. TET genes, and
      especially TET2, are frequently mutated in various cancers, but how the TET
      proteins contribute to prevent the onset and maintenance of these malignancies is
      largely unknown. Here, we highlight recent advances in understanding the
      physiological function of the TET proteins and their role in regulating DNA
      methylation and transcription. In addition, we discuss some of the key
      outstanding questions in the field.

PMID- 27036968
TI  - Corrigendum: Chaperone-mediated autophagy degrades mutant p53.
AB  - In the above-mentioned article, it has come to the authors' attention that,
      during the preparation of Figure 5C and Supplemental Figure S2C for the final
      version of this article, the authors unintentionally assembled incorrect tubulin
      immunoblots due to similarities in the markings or names, such as FLT3 versus FT,
      between two similar experiments. The amended versions of these figures are shown
      below. Neither the quantitative determinations nor the conclusions of this
      article are altered. The authors apologize for these errors.

PMID- 27036967
TI  - Splicing-independent loading of TREX on nascent RNA is required for efficient
      expression of dual-strand piRNA clusters in Drosophila.
AB  - The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA
      processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA
      transcribed by RNA polymerase II in a splicing-dependent fashion; however, how
      TREX functions is poorly understood. Here we show that Thoc5 and other TREX
      components are essential for the biogenesis of piRNA, a distinct class of small
      noncoding RNAs that control expression of transposable elements (TEs) in the
      Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis,
      resulting in derepression of multiple TE families, gametogenesis defects, and
      sterility. TREX components are enriched on piRNA precursors transcribed from dual
      strand piRNA clusters and colocalize in distinct nuclear foci that overlap with
      sites of piRNA transcription. The localization of TREX in nuclear foci and its
      loading on piRNA precursor transcripts depend on Cutoff, a protein associated
      with chromatin of piRNA clusters. Finally, we show that TREX is required for
      accumulation of nascent piRNA precursors. Our study reveals a novel splicing
      independent mechanism for TREX loading on nascent RNA and its importance in piRNA
      biogenesis.

PMID- 27036969
TI  - Erratum: The evolutionary turnover of recombination hot spots contributes to
      speciation in mice.
AB  - Due to a technical error in processing the figures in the above-mentioned
      article, Figures 3, A and B; 4B; 5B; and 6, A and C contained errors or missing
      elements. The errors have been corrected in both the PDF and full-text HTML files
      online.

PMID- 27036966
TI  - Genetic insights into the mechanisms of Fgf signaling.
AB  - The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine
      kinases is required throughout embryonic and postnatal development and also
      regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling
      causes many congenital disorders and underlies multiple forms of cancer.
      Understanding the mechanisms that govern Fgf signaling is therefore important to
      appreciate many aspects of Fgf biology and disease. Here we review the mechanisms
      of Fgf signaling by focusing on genetic strategies that enable in vivo analysis.
      These studies support an important role for Erk1/2 as a mediator of Fgf signaling
      in many biological processes but have also provided strong evidence for
      additional signaling pathways in transmitting Fgf signaling in vivo. 

PMID- 27036970
TI  - An Internet-based self-help intervention for people with HIV and depressive
      symptoms: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Many people living with HIV suffer from depressive symptoms. In a
      previous pilot study, self-help cognitive behavioral therapy (in booklet format)
      was found to be effective in treating depressive symptoms in people with HIV. We
      developed an online self-help program in Dutch and English (based on the booklet)
      for people with HIV and depressive symptoms. Besides the main question regarding
      the effectiveness of the program aimed at lowering depressive symptoms, sub
      questions will focus on the moderators of treatment success (for which patients
      is the program especially beneficial?) and the mechanisms of change underlying
      the treatment outcome (which mediators affect the outcome of treatment?). In this
      paper, the protocol of the study will be described. METHODS/DESIGN: The
      effectiveness of the program will be investigated by comparing the intervention
      group with a waiting list-control group in a randomized controlled design, by
      including a pretest and three post-tests. The self-help program contains four
      main components: activation, relaxation, changing maladaptive cognitions, and
      goal attainment. Participants with mild to moderate depressive symptoms will work
      on the program for 6 to 10 weeks, during which a coach will provide motivational
      support by telephone once a week. Participants in the control condition will
      receive weekly minimal support from a coach for 8 weeks, and after the second
      post-test, they can gain access to the self-help program. Depressive symptoms and
      possible mediators (e.g., activation, cognitive coping, self-efficacy, and goal
      adjustment) will be assessed by self-report three times during the
      intervention/waiting period and at the pretest and first post-test. DISCUSSION:
      The proposed study aims to evaluate the effectiveness of an online self-help
      intervention for people with HIV and depressive symptoms. If the intervention is
      shown to be effective, the program will be implemented. Consequently, many
      patients with HIV could be reached, and their psychological care may be improved.
      TRIAL REGISTRATION: Netherlands Trial Register: NTR5407.

PMID- 27036971
TI  - Can Targeting Stroma Pave the Way to Enhanced Antitumor Immunity and
      Immunotherapy of Solid Tumors?
AB  - Solid tumors are complex organ-like structures. The potential of normal
      neighboring cells to contribute to the initiation, progression, and metastasis of
      epithelial-derived carcinomas has long been appreciated. However, the role of
      host cells has proven complex. Through multiple local and systemic mechanisms,
      nontransformed host cells can promote transition from a tumor-resistant to tumor
      permissive environment, drive neoplastic transformation of epithelial cells,
      promote tumor growth, progression, and metastasis, but also constrain
      tumorigenesis. This complexity reflects the spatially and temporally dynamic
      involvement of multiple cell types and processes, including the development and
      recruitment of inflammatory, immune, endothelial, and mesenchymal stromal cells,
      and the remodeling of extracellular matrix. Our mechanistic understanding, as
      well as our ability to translate advances in our understanding of these
      mechanisms for therapeutic benefit, is rapidly advancing. Further insights will
      depend on delineating pathways that mediate the communication networks between
      inflammatory and immune cells with tumor and mesenchymal stromal cells and
      extracellular matrix. Here, we discuss the diversity of mesenchymal stromal cell
      populations and how context can dictate either their promotion or constraint of
      tumorigenesis. We review evidence for plasticity that allows for reprogramming of
      stromal cells and how tumor immunogenicity and desmoplasia influence the balance
      of immune-independent and immune-dependent regulation of tumor growth. The
      pivotal roles of matrix and mesenchymal stromal cells in modulating inflammation,
      antitumor immunity, and the efficacy of immune-based therapies are discussed.
      These concepts have emerged from data obtained from tumors of multiple organs,
      but we focus mostly on studies of pancreatic ductal adenocarcinomas.

PMID- 27036972
TI  - De-Risking Immunotherapy: Report of a Consensus Workshop of the Cancer
      Immunotherapy Consortium of the Cancer Research Institute.
AB  - With the recent FDA approvals of pembrolizumab and nivolumab, and a host of
      additional immunomodulatory agents entering clinical development each year, the
      field of cancer immunotherapy is changing rapidly. Strategies that can assist
      researchers in choosing the most promising drugs and drug combinations to move
      forward through clinical development are badly needed in order to reduce the
      likelihood of late-stage clinical trial failures. On October 5, 2014, the Cancer
      Immunotherapy Consortium of the Cancer Research Institute, a collaborative think
      tank composed of stakeholders from academia, industry, regulatory agencies, and
      patient interest groups, met to discuss strategies for de-risking immunotherapy
      development, with a focus on integrating preclinical and clinical studies, and
      conducting smarter early-phase trials, particularly for combination therapies.
      Several recommendations were made, including making better use of clinical data
      to inform preclinical research, obtaining adequate tissues for biomarker studies,
      and choosing appropriate clinical trial endpoints to identify promising drug
      candidates and combinations in nonrandomized early-phase trials.

PMID- 27036974
TI  - Does Core Length Taken per cc of Prostate Volume in Prostate Biopsy Affect the
      Diagnosis of Prostate Cancer?
AB  - INTRODUCTION: The aim of this study was to determine the minimal core length to
      be taken per cc of prostate volume for an effective prostate biopsy. PATIENTS AND
      METHODS: A retrospective analysis was performed on the records of 379 patients
      who underwent a first prostate biopsy with 12 to 16 cores under transrectal
      ultrasound guidance between September 2012 and April 2015. For each patient, the
      core length per cc of the prostate and the percentage of sampled prostate volume
      were calculated, and these values were compared between the patients with and
      without prostate cancer. RESULTS: A total of 348 patients were included in the
      study. Cancer was determined in 26.4% of patients. The mean core length taken per
      cc of prostate and the percentage of sampled prostate volume were determined to
      be 3.40 +/- 0.15 mm/cc (0.26%; range, 0.08-0.63 cc) in patients with cancer and
      2.75 +/- 0.08 mm/cc (0.20%; range, 0.04-0.66 cc) in patients without cancer (P =
      .000 and P = .000), respectively. Core length taken per cc of prostate of > 3.31
      mm/cc was found to be related to an increase in the rates of prostate cancer
      diagnosis (odds ratio, 2.84; 95% confidence interval, 1.68-4.78). The rate of
      cancer determination for core length taken per cc of prostate of < 3.31 mm/cc was
      19.9% and of > 3.31 mm/cc, 41.1%. CONCLUSIONS: Core length taken per cc of
      prostate and the percentage of sampled prostate volume are important morphometric
      parameters in the determination of prostate cancer. The results of study suggest
      a core length per cc of the prostate of > 3.31 mm/cc as a cutoff value for
      quality assurance.

PMID- 27036973
TI  - Phase 2 Study of Bevacizumab and Temsirolimus After VEGFR TKI in Metastatic Renal
      Cell Carcinoma.
AB  - BACKGROUND: Inhibiting VEGF and mammalian target of rapamycin (mTOR) pathways are
      standard treatment approaches for patients with metastatic renal cell carcinoma
      (mRCC). Here we report the activity and safety of the VEGF ligand inhibitor
      bevacizumab and the mTOR inhibitor temsirolimus combination in patients with
      clear cell (CC) and non-clear cell (NCC) mRCC whose disease had failed to respond
      to prior VEGF blockade. PATIENTS AND METHODS: In this phase 2 investigator
      initiated multicenter study, patients received bevacizumab and temsirolimus. The
      primary end point was 4-month progression-free survival (PFS) rate. Secondary end
      points included overall response rate, median overall survival (OS), toxicity,
      and correlative studies of biomarkers downstream of mTOR. RESULTS: Forty patients
      received at least 1 dose of therapy. Thirty-three (82.5%) had
      favorable/intermediate risk disease according to International Metastatic Renal
      Cell Carcinoma Database Consortium criteria, 13 (32.5%) with nccRCC histology.
      Nineteen (48.7%) had primary vascular endothelial growth factor receptor (VEGFR)
      tyrosine kinase inhibitor (TKI)-refractory disease. The 4-month PFS rate was 65%.
      Overall median PFS and OS were 5.6 and 12.2 months. Median PFS and OS were 6.5
      and 9.6 months in patients with primary VEGFR TKI-refractory disease, and 5.6
      months and 13.1 months in patients with nccRCC. Dose reductions were needed in
      80% of patients. Most frequent toxicities included fatigue, hypertension,
      dyslipidemia, and proteinuria. Dose discontinuation due to adverse events
      occurred in 27.5% of patients. Baseline tumor immunohistochemistry for phospho-S6
      protein was not associated with clinical benefit. CONCLUSION: Combining
      bevacizumab and temsirolimus in patients previously treated with VEGFR TKI was
      possible but with dose reductions and treatment discontinuations. This
      combination resulted in modest activity, including in patients with primary VEGF
      refractory disease and NCC histology.

PMID- 27036975
TI  - Should We Try Antiandrogen Withdrawal in Castration-Resistant Prostate Cancer
      Patients? Insights From a Retrospective Study.
AB  - BACKGROUND: It remains uncertain whether those with response to antiandrogen
      withdrawal (AAW) have a better prognosis. We investigated the predictors of a
      better response to AAW and overall survival after acquiring resistance to first
      line androgen deprivation therapy inpatients with castration-resistant prostate
      cancer (CRPC). PATIENTS AND METHODS: We retrospectively reviewed the medical
      records of 87 CRPC patients treated at Keio University Hospital. Sixty-seven of
      87 CRPC patients underwent AAW. We analyzed clinicopathologic parameters to
      identify predictors of survival in CRPC patients and investigated predictors of
      good response to AAW. RESULTS: Younger age, longer duration of androgen
      deprivation therapy before CRPC development, and better response to AAW were
      independent favorable prognostic factors for overall survival. Although better
      response to AAW was a favorable prognostic factor in this study, trying AAW was
      not significantly related to overall survival. Duration of hormone therapy was
      significantly longer in those whose disease responded to AAW (69.9 +/- 11.0
      months) than those with no response (45.3 +/- 5.2 months). CONCLUSION: The
      prognostic benefit of AAW was not clearly determined in this study. However, AAW
      might be beneficial in patients who have favorable prognostic factors for a
      response to AAW-that is, those who have received hormone therapy for a long
      period. However, AAW should not be done in patients who do not have favorable
      factors and who had a high prostate-specific antigen level at the time of their
      prostate cancer diagnosis.

PMID- 27036976
TI  - Prevalence and phylogenetic characterization of human enterovirus D68 among
      children with respiratory infection in Hong Kong.
AB  - This is the first report on the prevalence of human enterovirus D68 (EV-D68)
      among children with respiratory infection in Hong Kong. Among 1461 respiratory
      samples taken in 2014, EV-D68 was identified in 24 (1.64%) of them with a unusual
      seasonal pattern. Phylogenetic analysis indicated that all EV-D68 detected in
      this study belong to clade B. 

PMID- 27036977
TI  - Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid
      arthritis.
AB  - We report a patient who was being treated with rituximab for rheumatoid arthritis
      who developed Babesia microti infection that persisted for 26 months despite
      prolonged anti-babesia drug therapy. The explanation for the persistence was
      likely to have been the long-term immunocompromising effects of rituximab, as
      evidenced by seronegativity for B. microti antibodies that lasted for more than 1
      year after onset of infection. 

PMID- 27036978
TI  - Rifabutin and rifampin resistance levels and associated rpoB mutations in
      clinical isolates of Mycobacterium tuberculosis complex.
AB  - Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant
      Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer
      broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were
      RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A
      total of 42 unique single mutations or combinations of mutations were detected.
      The number of unique mutations identified exceeded that reported in any previous
      study. RFB and RIF MICs up to 8 MUg/mL by MGIT 960 were studied; the cut-off
      values for susceptibility to RIF and RFB were 1 MUg/mL and 0.5 MUg/mL,
      respectively. We identified 31 isolates resistant to RIF but susceptible to RFB
      with the mutations D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L,
      and two dual mutations (S522L + K527R and H526S + K527R). Clinical investigations
      using RFB to treat multidrug-resistant tuberculosis cases harboring those
      mutations are recommended. 

PMID- 27036979
TI  - Mitochondrial DNA damage and vascular function in patients with diabetes mellitus
      and atherosclerotic cardiovascular disease.
AB  - OBJECTIVE: Prior studies demonstrate mitochondrial dysfunction with increased
      reactive oxygen species generation in peripheral blood mononuclear cells in
      diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes
      atherosclerosis in animal models. Thus, we evaluated the relation of
      mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular
      function in patients with diabetes mellitus and with atherosclerotic
      cardiovascular disease. APPROACH AND RESULTS: We assessed non-invasive vascular
      function and mitochondrial DNA damage in 275 patients (age 57 +/- 9 years, 60 %
      women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes
      mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and
      diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or
      atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage
      measured by quantitative PCR in peripheral blood mononuclear cells was higher
      with clinical atherosclerosis alone (0.55 +/- 0.65), diabetes mellitus alone
      (0.65 +/- 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89
      +/- 1.32) as compared to control subjects (0.23 +/- 0.64, P < 0.0001). In
      multivariable models adjusting for age, sex, and relevant cardiovascular risk
      factors, clinical atherosclerosis and diabetes mellitus remained associated with
      higher mitochondrial DNA damage levels (beta = 0.14 +/- 0.13, P = 0.04 and beta =
      0.21 +/- 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was
      associated with higher baseline pulse amplitude, a measure of arterial
      pulsatility, but not with flow-mediated dilation or hyperemic response, measures
      of vasodilator function. CONCLUSIONS: We found greater mitochondrial DNA damage
      in patients with diabetes mellitus and clinical atherosclerosis. The association
      of mitochondrial DNA damage and baseline pulse amplitude may suggest a link
      between mitochondrial dysfunction and excessive small artery pulsatility with
      potentially adverse microvascular impact.

PMID- 27036980
TI  - Distinction between contrast staining and hemorrhage after endovascular stroke
      treatment: one CT is not enough.
AB  - BACKGROUND: Postinterventional cerebral hyperdensities (PCHDs) are a common
      finding after endovascular stroke treatment. There is uncertainty about the
      extent to which PCHDs correspond to hemorrhage or contrast staining. Our aim was
      to evaluate the use of PCHD density on immediate postinterventional CT, and PCHD
      evolution on follow-up CT for differentiating contrast staining from hemorrhage
      after endovascular treatment. METHODS: We retrospectively reviewed the imaging
      data of 84 patients who underwent endovascular treatment for acute arterial
      ischemic stroke in the anterior circulation and who received an immediate
      postinterventional CT, a follow-up CT within 36 h, and a follow-up MRI within 10
      days. RESULTS: PCHDs were seen in 62 of 84 patients in a total of 130 Alberta
      Stroke Program Early CT Score (ASPECTS) areas. A specificity of 100% to predict
      hemorrhage was only seen for PCHDs with densities <40 HU (for ruling hemorrhage
      out) and >=140 HU (for ruling hemorrhage in), at the cost of a low sensitivity of
      1.1% and 2.4%, respectively. Persisting PCHDs correlated with hemorrhage with a
      specificity of 93.3% and a sensitivity of 62.5%. When follow-up CT was performed
      at least 19 h after the first CT, persisting PCHDs correlated with hemorrhage
      with a specificity of 100% and a sensitivity of 62.5%. CONCLUSIONS: There are no
      density thresholds for PCHDs that allow predicting the absence or presence of
      hemorrhage with 100% specificity and acceptable sensitivity. A CT scan performed
      at least 19-24 h after endovascular therapy is the only reliable method to
      differentiate contrast staining from hemorrhage.

PMID- 27036981
TI  - Cardiovascular risk assessment among rural population: findings from a cohort
      study in a peripheral region of Bangladesh.
AB  - OBJECTIVES: The incidences of non-communicable diseases including cardiovascular
      diseases (CVDs) is increasing in Bangladesh. The reasons for this increasing
      trend need to be explored. The aim of this study is to assess the risk of CVDs
      among a peripheral rural Bangladeshi population and to explore the
      sociodemographic, anthropometric and clinical variables associated with increased
      risk. STUDY DESIGN: Cohort study. METHODS: From a cohort of 190,471 individuals
      of all ages, originally included in a diabetic eye disease program initiated in
      2008-2009, a purposive sub-cohort of 66,710 individuals, aged 31-74 years was
      recruited. During 2011-2012 these participants were assessed for CVDs using the
      WHO's risk assessment tool designed for primary care settings in low resource
      societies. Participant characteristics associated with higher risk were explored
      using univariable and multivariable regression analysis. RESULTS: Out of all
      (95.5% participation rate) participants 1170 (1.84%) were found to be at high
      risk for CVD. The prevalence of hypertension (HTN), pre-HTN, obesity, underweight
      and self-reported DM were 8.9%, 15.2%, 9.6%, 7.8% and 0.5% respectively, among
      the study population. In multivariable regression analysis female sex, older age,
      temporary housing structure (i.e., tin shed), extremes of BMI (both underweight
      and obese) and central obesity were associated with higher risk for CVDs.
      CONCLUSIONS: The prevalence of CVD risk factors and high CVD risk individuals in
      this cohort was found to be lower than previous studies. It may be the effects of
      urbanization are yet to reach this relatively traditional rural population. This
      study adds to the literature on use of the WHO risk assessment tool.

PMID- 27036982
TI  - Hidden prevalence of chronic kidney disease in hypertensive patients: the
      strategic role of primary health care.
AB  - OBJECTIVE: To identify the hidden prevalence of chronic kidney disease (CKD) in
      hypertensive patients. STUDY DESIGN: Cross-sectional study of individuals with
      systemic arterial hypertension (SAH) who were registered for primary health care
      (PHC). METHODS: In total, 293 individuals participated. Data were collected
      through interviews, as well as biochemical and anthropometric assessments. The
      CKD-EPI formula was used to identify the occurrence of CKD. Pearson's chi-squared
      test or Fisher's exact test were used to compare proportions. Prevalence ratios
      were estimated with a confidence interval of 95% for associations between the
      explanatory variables and CKD. RESULTS: Most of the individuals assessed were
      female (74%), elderly (69%), with a low income (90%), low education levels (84%)
      and overweight (66.9%). A CKD prevalence of 38.6% (95% CI: 33.0-44.2) was found
      and approximately 14% were at an advanced stage of the disease. Upon comparison
      of the variables in the different stages of CKD, statistically significant
      association could be suggested between CKD and age, education, alcohol intake,
      overweight individuals, cardiovascular risk, abnormal creatinine and abnormal
      microalbuminuria. When the prevalence ratio was assessed, association could be
      suggested between CKD and age, and CKD and creatinine. CONCLUSION: The high
      hidden prevalence of CKD confirms the need to train health professionals involved
      in the treatment of SAH through PHC, enabling the prevention and diagnosis of CKD
      in its early stages.

PMID- 27036984
TI  - UNGASS: time to put HIV at the forefront of drug policy.

PMID- 27036983
TI  - Preclinical Dose-Escalation Study of Intravitreal AAV-RS1 Gene Therapy in a Mouse
      Model of X-linked Retinoschisis: Dose-Dependent Expression and Improved Retinal
      Structure and Function.
AB  - Gene therapy for inherited retinal diseases has been shown to ameliorate
      functional and structural defects in both animal models and in human clinical
      trials. X-linked retinoschisis (XLRS) is an early-age onset macular dystrophy
      resulting from loss of an extracellular matrix protein (RS1). In preparation for
      a human clinical gene therapy trial, we conducted a dose-range efficacy study of
      the clinical vector, a self-complementary AAV delivering a human retinoschisin
      (RS1) gene under control of the RS1 promoter and an interphotoreceptor binding
      protein enhancer (AAV8-scRS/IRBPhRS), in the retinoschisin knockout (Rs1-KO)
      mouse. The therapeutic vector at 1 * 10(6) to 2.5 * 10(9) (1E6-2.5E9) vector
      genomes (vg)/eye or vehicle was administered to one eye of 229 male Rs1-KO mice
      by intravitreal injection at 22 +/- 3 days postnatal age (PN). Analysis of
      retinal function (dark-adapted electroretinogram, ERG), structure (cavities and
      outer nuclear layer thickness) by in vivo retinal imaging using optical coherence
      tomography, and retinal immunohistochemistry (IHC) for RS1 was done 3-4 months
      and/or 6-9 months postinjection (PI). RS1 IHC staining was dose dependent across
      doses >=1E7 vg/eye, and the threshold for significant improvement in all measures
      of retinal structure and function was 1E8 vg/eye. Higher doses, however, did not
      produce additional improvement. At all doses showing efficacy, RS1 staining in
      Rs1-KO mouse was less than that in wild-type mice. Improvement in the ERG and RS1
      staining was unchanged or greater at 6-9 months than at 3-4 months PI. This study
      demonstrates that vitreal administration of AAV8 scRS/IRBPhRS produces
      significant improvement in retinal structure and function in the mouse model of
      XLRS over a vector dose range that can be extended to a human trial. It indicates
      that a fully normal level of RS1 expression is not necessary for a therapeutic
      effect. 

PMID- 27036985
TI  - Tenofovir alafenamide: safer, but questions remain.

PMID- 27036986
TI  - Is HIV-1C a risk factor for protease inhibitor failure?

PMID- 27036987
TI  - Good news for retention of women on option B+ in Malawi.

PMID- 27036988
TI  - Community viral load as an index of HIV transmission potential.

PMID- 27036989
TI  - Is sub-Saharan Africa ready for pre-exposure prophylaxis?

PMID- 27036990
TI  - Rethinking HIV pre-exposure prophylaxis prevention strategy.

PMID- 27036991
TI  - Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate
      given as fixed-dose combinations containing emtricitabine as backbones for
      treatment of HIV-1 infection in virologically suppressed adults: a randomised,
      double-blind, active-controlled phase 3 trial.
AB  - BACKGROUND: Emtricitabine with tenofovir disoproxil fumarate is a standard-of
      care nucleoside reverse transcriptase inhibitor (NRTI) backbone. However,
      tenofovir disoproxil fumarate is associated with renal and bone toxic effects;
      the novel prodrug tenofovir alafenamide achieves 90% lower plasma tenofovir
      concentrations. We aimed to further assess safety and efficacy of fixed-dose
      combination emtricitabine with tenofovir alafenamide in patients switched from
      emtricitabine with tenofovir disoproxil fumarate. METHODS: In this controlled,
      double-blind, multicentre phase 3 study, we recruited virologically suppressed
      (HIV RNA <50 copies per mL) patients with HIV aged 18 years and older receiving
      regimens containing fixed-dose combination emtricitabine with tenofovir
      disoproxil fumartate from 78 sites in North America and Europe. Patients were
      randomly assigned (1:1) to switch to fixed-dose 200 mg emtricitabine with 10 mg
      or 25 mg tenofovir alafenamide or to continue 200 mg emtricitabine with 200 mg or
      300 mg tenofovir disoproxil fumarate, while remaining on the same third agent for
      96 weeks. Randomisation was done by a computer-generated allocation sequence and
      was stratified by the third agent (boosted protease inhibitor vs other agent).
      Investigators, patients, and study staff giving treatment, assessing outcomes,
      and collecting data were masked to treatment group. The primary outcome was the
      proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week
      48 as defined by the US Food and Drug Administration snapshot algorithm with a
      prespecified non-inferiority margin of 10%. The primary efficacy endpoint was
      analysed with the per-protocol analysis set, whereas the safety analysis included
      all randomly assigned patients who received at least one dose of study drug. This
      study is registered with ClinicalTrials.gov, number NCT02121795. FINDINGS: We
      recruited patients between May 6, 2011, and Sept 11, 2014; 780 were screened and
      668 were randomly assigned to receive either tenofovir alafenamide (n=333) or
      tenofovir disoproxil fumarate (n=330). Through week 48, virological success (HIV
      1 RNA <50 copies per mL) was maintained in 314 (94%) of patients in the tenofovir
      alafenamide group compared with 307 (93%) in the tenofovir disoproxil fumarate
      group (difference 1.3%, 95% CI -2.5 to 5.1), showing non-inferiority of tenofovir
      alafenamide to tenofovir disproxil fumarate. Seven patients in the tenofovir
      alafenamide (2%) and three (1%) in the tenofovir disoproxil fumarate group
      discontinued due to adverse events. There were no cases of proximal renal
      tubulopathy in either group. INTERPRETATION: In patients switching from
      emtricitabine with tenofovir disoproxil fumarate to emtricitabine with tenofovir
      alafenamide, high rates of virological suppression were maintained. With its
      safety advantages, fixed-dose emtricitabine with tenofovir alafenamide has the
      potential to become an important NRTI backbone. FUNDING: Gilead Sciences.

PMID- 27036992
TI  - Virological failure in patients with HIV-1 subtype C receiving antiretroviral
      therapy: an analysis of a prospective national cohort in Sweden.
AB  - BACKGROUND: People with HIV-1 in low-income and middle-income countries
      increasingly need second-line regimens with boosted protease inhibitors. However,
      data are scarce for treatment response in patients with HIV-1 subtype C (HIV-1C),
      which is predominant in these regions. We aimed to examine factors associated
      with virological failure in patients in a standardised national health-care
      setting. METHODS: We analysed data for participants in InfCare HIV, a prospective
      national cohort that includes more than 99% of people with HIV in Sweden. We
      extracted data for the cohort from the InfCare HIV database on Jan 14, 2015.
      Baseline was initiation of antiretroviral therapy. We used logistic regression to
      assess factors associated with primary virological failure (failure to suppress
      HIV-1 within 9 months) in patients with HIV-1B and HIV-1C and calculated odds
      ratios (OR) for failure. We also used Cox regression models to calculate hazard
      ratios (HR) for time-to-secondary virological failure (detectable viral load
      after initial virological suppression). We did homology-based molecular modelling
      to assess docking. FINDINGS: We included 1077 patients with HIV-1B and 596 with
      HIV-1C. In multivariate regression analysis, pre-therapy higher viral load (OR
      1.82, 95% CI 1.49-2.21; p<0.0001), subtype C infection (1.75, 1.06-2.88;
      p=0.028), and boosted protease inhibitor-based regimens (1.55, 1.45-2.11;
      p=0.004) were associated with increased risk of primary virological failure.
      Individuals with HIV-1C who were given therapy with boosted protease inhibitors
      had earlier time-to-secondary virological failure than did those with HIV-1B
      given similar regimens (adjusted HR 1.92, 95% CI 1.30-2.83; p=0.002). Molecular
      modelling suggested lower affinity for protease inhibitors to HIV-1C protease
      than to HIV-1B. INTERPRETATION: Our findings suggest an increased risk of
      virological failure in patients with HIV-1C, especially in those on boosted
      protease inhibitor-based regimens. Future studies should further dissect the
      biochemical and viral mechanisms of resistance to protease inhibitors in patients
      with non-B subtypes of HIV-1, including clinical studies to assess the efficacy
      of boosted protease inhibitor-based regimens in low-income and middle income
      countries. FUNDING: Karolinska Institutet Research Foundation, Swedish Research
      Council, Stockholm County Council, Swedish Physicians against AIDS, US National
      Institutes of Health, University of Missouri.

PMID- 27036993
TI  - Retention in care during the first 3 years of antiretroviral therapy for women in
      Malawi's option B+ programme: an observational cohort study.
AB  - BACKGROUND: Studies of Malawi's option B+ programme for HIV-positive pregnant and
      breastfeeding women have reported high loss to follow-up during pregnancy and at
      the start of antiretroviral therapy (ART), but few data exist about retention
      during breastfeeding and after weaning. We examined loss to follow-up and
      retention in care in patients in the option B+ programme during their first 3
      years on ART. METHODS: We analysed two data sources: aggregated facility-level
      data about patients in option B+ who started ART between Oct 1, 2011, and June
      30, 2012, at 546 health facilities; and patient-level data from 20 large
      facilities with electronic medical record system for HIV-positive women who
      started ART between Sept 1, 2011, and Dec 31, 2013, under option B+ or because
      they had WHO clinical stages 3 or 4 disease or had CD4 counts of less than 350
      cells per MUL. We used facility-level data to calculate representative estimates
      of retention and loss to follow-up. We used patient-level data to study temporal
      trends in retention, timing of loss to follow-up, and predictors of no follow-up
      and loss to follow-up. We defined patients who were more than 60 days late for
      their first follow-up visit as having no follow-up and patients who were more
      than 60 days late for a subsequent visit as being lost to follow-up. We
      calculated proportions and cumulative probabilities of patients who had died,
      stopped ART, had no follow-up, were lost to follow-up, or were retained alive on
      ART for 36 months. We calculated odds ratios and hazard ratios to examine
      predictors of no follow-up and loss to follow-up. FINDINGS: Analysis of facility
      level data about patients in option B+ who had not transferred to a different
      facility showed retention in care to be 76.8% (20 475 of 26,658 patients) after
      12 months, 70.8% (18,306 of 25,849 patients) after 24 months, and 69.7% (17,787
      of 25,535 patients) after 36 months. Patient-level data included 29,145 patients.
      14,630 (50.2%) began treatment under option B+. Patients in option B+ had a
      higher risk of having no follow-up and, for the first 2 years of ART, higher risk
      of loss to follow-up than did patients who started ART because they had CD4
      counts less than 350 cells per MUL or WHO clinical stage 3 or 4 disease. Risk of
      loss to follow-up during the third year was low and similar for patients retained
      for 2 years. Retention rates did not change as the option B+ programme matured.
      INTERPRETATION: Our data suggest that pregnant and breastfeeding women who start
      ART immediately after they are diagnosed with HIV can be retained on ART through
      the option B+ programme, even after many have stopped breastfeeding.
      Interventions might be needed to improve retention in the first year on ART in
      option B+. FUNDING: Bill & Melinda Gates Foundation, Partnerships for Enhanced
      Engagement in Research Health, and National Institute of Allergy and Infectious
      Diseases.

PMID- 27036994
TI  - Community viral load, antiretroviral therapy coverage, and HIV incidence in
      India: a cross-sectional, comparative study.
AB  - BACKGROUND: HIV incidence is the best measure of treatment-programme
      effectiveness, but its measurement is difficult and expensive. The concept of
      community viral load as a modifiable driver of new HIV infections has attracted
      substantial attention. We set out to compare several measures of community viral
      load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in
      high-risk populations. METHODS: We analysed data from a sample of people who
      inject drugs and men who have sex with men, who were participants of the baseline
      assessment of a cluster-randomised trial in progress across 22 cities in India
      (ClinicalTrials.gov number NCT01686750). We recruited the study population by use
      of respondent-driven sampling and did the baseline assessment at 27 community
      based sites (12 for men who have sex with men and 15 for people who inject
      drugs). We estimated HIV incidence with a multiassay algorithm and calculated
      five community-based measures of HIV control: mean log10 HIV RNA in participants
      with HIV in a community either engaged in care (in-care viral load), aware of
      their status but not necessarily in care (aware viral load), or all HIV-positive
      individuals whether they were aware, in care, or not (population viral load);
      participants with HIV in a community with HIV RNA more than 150 copies per mL
      (prevalence of viraemia); and the proportion of participants with HIV who self
      reported ART use in the previous 30 days (population ART coverage). All
      participants were tested for HIV, with additional testing in HIV-positive
      individuals. We assessed correlations between the measures and HIV incidence with
      Spearman correlation coefficients and linear regression analysis. FINDINGS:
      Between Oct 1, 2012, and Dec 19, 2013, we recruited 26,503 participants, 12,022
      men who have sex with men and 14,481 people who inject drugs. Median incidence of
      HIV was 0.87% (IQR 0.40-1.17) in men who have sex with men and 1.43% (0.60-4.00)
      in people who inject drugs. Prevalence of viraemia was more strongly correlated
      with HIV incidence (correlation 0.81, 95% CI 0.62-0.91; p<0.0001) than all other
      measures, although correlation was significant with aware viral load (0.59, 0.27
      0.79; p=0.001), population viral load (0.51, 0.16-0.74; p=0.007), and population
      ART coverage (-0.54, -0.76 to -0.20; p=0.004). In-care viral load was not
      correlated with HIV incidence (0.29, -0.10 to 0.60; p=0.14). With regression
      analysis, we estimated that to reduce HIV incidence by 1 percentage point in a
      community, prevalence of viraemia would need to be reduced by 4.34%, and ART use
      in HIV-positive individuals would need to increase by 19.5%. INTERPRETATION:
      Prevalence of viraemia had the strongest correlation with HIV incidence in this
      sample and might be a useful measure of the effectiveness of a treatment
      programme. FUNDING: US National Institutes of Health, Elton John AIDS Foundation.

PMID- 27036995
TI  - Does knee awareness differ between different knee arthroplasty prostheses? A
      matched, case-control, cross-sectional study.
AB  - BACKGROUND: Low knee awareness after Total Knee Arthroplasty (TKA) has become the
      ultimate goal in trying to achieve a natural feeling knee that meet patient
      expectations. To accommodate this manufacturers of TKAs have developed new
      prosthetic designs that potentially could give patients a more natural feeling
      knee during activities. The purpose af this study was to compare the Forgotten
      Joint Score (FJS) and Oxford Knee Score (OKS) of patients treated with a previous
      generation standard Cruciate Retaining (CR) TKA to the scores obtained by
      patients treated with a newer generation CR TKA or a mobile bearing CR TKA.
      METHODS: We identified all patients receiving a new generation CR TKA or mobile
      bearing TKA at our institution between 2010 and 2012. These were matched to a
      population of patients receiving a standard CR TKA regarding age, gender, year of
      surgery, Kellgren-Lawrence (KL) grade and pre- and postoperative knee alignment.
      Patients were asked to complete the FJS and OKS questionnaires. Of the 316
      patients completing the survey 64 standard CR TKAs to 35 new generation CR TKAs
      and 121 standard CR TKAs to 68 mobile bearing TKAs were matched. The FJS and OKS
      scores of the three TKA designs were compared. RESULTS: When comparing the new
      generation CR TKAs to the standard CR TKAs we found statistically significant
      higher OKS and FJS scores (6 (p = 0.04) and 16 (p = 0.03) points respectively)
      for the new generation CR TKAs. When comparing the mobile bearing TKAs to the
      standard CR TKAs we found a statistically significant higher OKS score (3 points,
      p = 0.04), and a higher but non-significant FJS score (4 points, p = 0.48) for
      the mobile bearing TKAs. CONCLUSIONS: Patients receiving the new generation CR
      TKA obtained higher FJS and OKS scores when compared to patients receiving a
      standard CR TKA, indicating that the use of this newer prosthetic design
      facilitate less knee awareness and better function after TKA.

PMID- 27036996
TI  - Modeling municipal solid waste collection: A generalized vehicle routing model
      with multiple transfer stations, gather sites and inhomogeneous vehicles in time
      windows.
AB  - Municipal Solid Waste (MSW) collection is a necessary process in any municipality
      resulting in the quality-of-life, economic aspects and urban structuralization.
      The intrinsic nature of MSW collection relates to the development of effective
      vehicle routing models that optimize the total traveling distances of vehicles,
      the environmental emission and the investment costs. In this article, we propose
      a generalized vehicle routing model including multiple transfer stations, gather
      sites and inhomogeneous vehicles in time windows for MSW collection. It takes
      into account traveling in one-way routes, the number of vehicles per m(2) and
      waiting time at traffic stops for reduction of operational time. The proposed
      model could be used for scenarios having similar node structures and vehicles'
      characteristics. A case study at Danang city, Vietnam is given to illustrate the
      applicability of this model. The experimental results have clearly shown that the
      new model reduces both total traveling distances and operational hours of
      vehicles in comparison with those of practical scenarios. Optimal routes of
      vehicles on streets and markets at Danang are given. Those results are
      significant to practitioners and local policy makers. 

PMID- 27036997
TI  - PLA coated paper containing active inorganic nanoparticles: Material
      characterization and fate of nanoparticles in the paper recycling process.
AB  - For paper and paperboard packaging, recyclability plays an important role in
      conserving the resources and reducing the environmental impacts. Therefore, when
      it comes to the nano-enabled paper packaging material, the recyclability issue
      should be properly addressed. This study represents our first report on the fate
      of nanomaterials in paper recycling process. The packaging material of concern is
      a PLA (Polylactic Acid) coated paper incorporating zinc oxide nanoparticles in
      the coating layer. The material was characterised and assessed in a lab-scale
      paper recycling line. The recyclability test was based on a method adapted from
      ATICELCA MC501-13, which enabled to recover over 99% of the solids material. The
      mass balance result indicates that 86-91% zinc oxide nanoparticles ended up in
      the rejected material stream, mostly embedded within the polymer coating; whereas
      7-16% nanoparticles ended up in the accepted material stream. Besides, the
      tensile strength of the recycled handsheets suggests that the nano-enabled
      coating had no negative impacts on the recovered fibre quality. 

PMID- 27036998
TI  - Fatal Clostridium perfringens sepsis due to emphysematous gastritis and
      literature review.
AB  - A 76-year-old female patient was admitted to the Level I Emergency Department of
      University of Szeged with severe abdominal pain and vomiting. The clinical
      assessment with laboratory tests and radiological investigations confirmed severe
      sepsis associated with intravascular hemolysis and multiorgan failure and acute
      pancreatitis. On the abdominal CT, besides of other abnormalities, the presence
      of gas bubbles in the stomach, small intestines and liver were seen. The gastric
      alterations pointed to emphysematous gastritis. Despite of the medical treatment,
      the patient's condition quickly deteriorated and eight hours after admission the
      patient died. The autopsy evaluation revealed systemic infection of abdominal
      origin caused by gas-producing Gram-positive bacteria, and the post-mortem
      microbiological cultures confirmed the presence of Cloctridium perfringens in
      many abdominal organs. Emphysematous gastritis seemed to be the primary
      infectious focus. 

PMID- 27036999
TI  - Effects of gonadotropin-releasing hormone agonist and antagonist on ovarian
      activity in a mouse model for polycystic ovary.
AB  - PCOS is a major cause of anovulatory infertility in women in their reproductive
      age. However, its etiology and pathophysiology remain uncertain. The immature
      mice chronically injected with DHEA, termed as PCO-mice, develop numerous large
      cystic follicles, high circulating androgen and anovulation similar to PCOS in
      women. Although PCO-mice show decreased ovarian GnRH I-receptor in immunoblot but
      show increased immunostaining for GnRH I-receptor in oocytes of cystic follicles.
      PCO-mice show reduced ovarian LH receptor expression, circulating estradiol and
      progesterone level compared to normal mice injected with vehicle only. The
      treatment with low dose of GnRH-Agonist in PCO-mice restores ovarian LH receptor
      expression to the level of normal mice and promote ovulation and formation of
      functional corpus luteum. GnRH-Antagonist although cause ovulation in PCO-mice
      but does not restore LH receptor expression to the level of normal mice, and they
      show low circulating progesterone and hypertrophied vacuolated corpus luteum. Our
      study suggests that GnRH-agonist restores ovulation in PCO-mice and produces
      biphasic and beneficial effect over the use of GnRH-Antagonist.

PMID- 27037000
TI  - miR-539 inhibits prostate cancer progression by directly targeting SPAG5.
AB  - BACKGROUND: We conducted multiple microarray datasets analyses from clinical and
      xenograft tumor tissues to search for disease progression-driving oncogenes in
      prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our
      attention. SPAG5 was recently identified as an oncogene participating in lung
      cancer and cervical cancer progression. However, the roles of SPAG5 in PCa
      progression remain unknown. METHODS: SPAG5 expression level in clinical primary
      PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal
      prostate tissues was investigated. We established multiple in vivo xenografts
      models using patient-derived tissues and investigated SPAG5 expression trend in
      these models. We also investigated the functions of SPAG5 in vivo and in vitro
      studies. Luciferase reporter assays were performed to investigate potential
      miRNAs that can regulate SPAG5. RESULTS: We identified that SPAG5 expression was
      gradually increased in PCa progression and its level was significantly associated
      with lymph node metastasis, clinical stage, Gleason score, and biochemical
      recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit
      PCa cell proliferation, migration, and invasion in vitro and supress tumor growth
      and metastasis in vivo. We identified that miR-539 can directly target SPAG5.
      Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and
      the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539
      on PCa cell proliferation and metastasis. CONCLUSION: Our results collectively
      showed a progression-driving role of SPAG5 in PCa which can be regulated by miR
      539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target
      for PCa.

PMID- 27037001
TI  - Extract from a mutant Rhodobacter sphaeroides as an enriched carotenoid source.
AB  - BACKGROUND: The extract LycogenTM from the phototrophic bacterium Rhodobacter
      sphaeroides (WL-APD911) has attracted significant attention because of its
      promising potential as a bioactive mixture, attributed in part to its anti
      inflammatory properties and anti-oxidative activity. OBJECTIVE: This study aims
      to investigate the components of LycogenTM and its anti-inflammatory properties
      and anti-oxidative activity. DESIGN AND RESULTS: The mutant strain R. sphaeroides
      (WL-APD911) whose carotenoid 1,2-hydratase gene has been altered by chemical
      mutagenesis was used for the production of a new carotenoid. The strain was grown
      at 30 degrees C on Luria-Bertani (LB) agar plates. After a 4-day culture period,
      the mutant strain displayed a 3.5-fold increase in carotenoid content, relative
      to the wild type. In the DPPH test, LycogenTM showed more potent anti-oxidative
      activity than lycopene from the wild-type strain. Primary skin irritation test
      with hamsters showed no irritation response in hamster skins after 30 days of
      treatment with 0.2% LycogenTM. Chemical investigations of LycogenTM using nuclear
      magnetic resonance (NMR) (1)H, (13)C, and COSY/DQCOSY spectra have identified
      spheroidenone and methoxyneurosporene. Quantitative analysis of these identified
      compounds based on spectral intensities indicates that spheroidenone and
      methoxyneurosporene are major components (approximately 1:1); very small
      quantities of other derivatives are also present in the sample. CONCLUSIONS: In
      this study, we identified the major carotenoid compounds contained in LycogenTM,
      including spheroidenone and methoxyneurosporene by high-resolution NMR
      spectroscopy analysis. The carotenoid content of this mutant strain of R.
      sphaeroides was 3.5-fold higher than that in normal strain. Furthermore,
      LycogenTM from the mutant strain is more potent than lycopene from the wild-type
      strain and does not cause irritation in hamster skins. These findings suggest
      that this mutant strain has the potential to be used as an enriched carotenoid
      source.

PMID- 27037003
TI  - Potential treatment for a subtype of glioblastoma tumours.

PMID- 27037002
TI  - Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure
      response of obese subjects, even after following an energy-restricted diet.
AB  - BACKGROUND: Cardiometabolic profile is usually altered in obesity. Interestingly,
      the consumption of flavanol-rich foods might be protective against those
      metabolic alterations. OBJECTIVE: To evaluate the postprandial cardiometabolic
      effects after the acute consumption of cocoa extract before and after 4 weeks of
      its daily intake. Furthermore, the bioavailability of cocoa extract was
      investigated. DESIGN: Twenty-four overweight/obese middle-aged subjects
      participated in a 4-week intervention study. Half of the volunteers consumed a
      test meal enriched with 1.4 g of cocoa extract (415 mg flavanols), while the rest
      of the volunteers consumed the same meal without the cocoa extract (control
      group). Glucose and lipid profile, as well as blood pressure and cocoa
      metabolites in plasma, were assessed before and at 60, 120, and 180 min post
      consumption, at the beginning of the study (Postprandial 1) and after following a
      4-week 15% energy-restricted diet including meals containing or not containing
      the cocoa extract (Postprandial 2). RESULTS: In the Postprandial 1 test, the area
      under the curve (AUC) of systolic blood pressure (SBP) was significantly higher
      in the cocoa group compared with the control group (p=0.007), showing significant
      differences after 120 min of intake. However, no differences between groups were
      observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of
      SBP (AUC_Postprandial 2-AUC_Postprandial 1) was higher in the cocoa group
      (p=0.016). Furthermore, cocoa-derived metabolites were detected in plasma of the
      cocoa group, while the absence or significantly lower amounts of metabolites were
      found in the control group. CONCLUSIONS: The daily consumption of cocoa extract
      within an energy-restricted diet for 4 weeks resulted in a greater reduction of
      postprandial AUC of SBP compared with the effect of energy-restricted diet alone
      and independently of body weight loss. These results suggest the role of cocoa
      flavanols on postprandial blood pressure homeostasis.

PMID- 27037004
TI  - Sugar tax in the UK.

PMID- 27037005
TI  - 2016 Annual Meeting of the Society of Gynecologic Oncology.

PMID- 27037006
TI  - Quality of neck dissection operative reports.
AB  - PURPOSE: The operative report is the official documentation of an operation and a
      key form of surgical communication. The objective of this study is to assess
      completeness of operative reports for neck dissections. METHODS: This is a
      retrospective review of narrative operative reports for neck dissections for head
      and neck squamous cell carcinoma. Forty-nine operative reports were provided by
      ten surgeons from seven academic institutions. Operative report completeness was
      expressed as a percentage of variables from a standardized checklist created by
      an expert panel. RESULTS: For level 1 dissections, most reports identified
      critical structures, such as the marginal mandibular nerve (84%) and the
      submandibular gland (84%). Of the cases that involved submandibular gland
      excision, reports were deficient in identification of the lingual nerve (74%),
      hypoglossal nerve (58%) and submandibular duct (22%). For neck dissections
      involving levels 2, 3 and 4, most described identifying spinal accessory nerve
      (92%) and internal jugular vein (98%), whereas fewer described identification of
      carotid artery or vagus nerve (67%), ansa cervicalis (31%), or cervical rootlets
      (48%). For level 5 dissections, only 75% of reports reported identification of
      spinal accessory nerve. Sixty percent of reports provided some description of the
      removed lymph nodes, but there was no consistency in terminology or definitions.
      Overall completeness of all NORs was 64% (40%-79%, SD 9%). CONCLUSIONS: There is
      heterogeneity and incompleteness in neck dissection operative reports across
      surgeons and institutions, despite being a crucial record of head and neck cancer
      treatment.

PMID- 27037007
TI  - The Influence of Disease Severity of Preceding Clinical Cases on Pathologists'
      Medical Decision Making.
AB  - BACKGROUND: Medical decision making may be influenced by contextual factors. We
      evaluated whether pathologists are influenced by disease severity of recently
      observed cases. METHODS: Pathologists independently interpreted 60 breast biopsy
      specimens (one slide per case; 240 total cases in the study) in a prospective
      randomized observational study. Pathologists interpreted the same cases in 2
      phases, separated by a washout period of >6 months. Participants were not
      informed that the cases were identical in each phase, and the sequence was
      reordered randomly for each pathologist and between phases. A consensus reference
      diagnosis was established for each case by 3 experienced breast pathologists.
      Ordered logit models examined the effect the pathologists' diagnoses on the
      preceding case or the 5 preceding cases had on their diagnosis for the subsequent
      index case. RESULTS: Among 152 pathologists, 49 provided interpretive data in
      both phases I and II, 66 from only phase I, and 37 from phase II only. In phase
      I, pathologists were more likely to indicate a more severe diagnosis than the
      reference diagnosis when the preceding case was diagnosed as ductal carcinoma in
      situ (DCIS) or invasive cancer (proportional odds ratio [POR], 1.28; 95%
      confidence interval [CI], 1.15-1.42). Results were similar when considering the
      preceding 5 cases and for the pathologists in phase II who interpreted the same
      cases in a different order compared with phase I (POR, 1.17; 95% CI, 1.05-1.31).
      CONCLUSION: Physicians appear to be influenced by the severity of previously
      interpreted test cases. Understanding types and sources of diagnostic bias may
      lead to improved assessment of accuracy and better patient care.

PMID- 27037008
TI  - Corrigendum to "Haloperidol challenge in healthy male humans: a functional
      magnetic resonance imaging study" [Neurosci. Lett. 340 (3) (2003) 193-196].

PMID- 27037009
TI  - Electrical stimulation with non-implanted electrodes for overactive bladder in
      adults.
AB  - BACKGROUND: Several options exist for managing overactive bladder (OAB),
      including electrical stimulation (ES) with non-implanted devices, conservative
      treatment and drugs. Electrical stimulation with non-implanted devices aims to
      inhibit contractions of the detrusor muscle, potentially reducing urinary
      frequency and urgency. OBJECTIVES: To determine the effectiveness of: ES with non
      implanted electrodes compared with placebo or any other active treatment for OAB;
      ES added to another intervention compared with the other intervention alone;
      different methods of ES compared with each other. SEARCH METHODS: We searched the
      Cochrane Incontinence Group Specialised Register, which contains trials
      identified from the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, MEDLINE In-Process, ClinicalTrials.gov, WHO ICTRP and handsearching of
      journals and conference proceedings (searched 10 December 2014). We searched the
      reference lists of relevant articles and contacted specialists in the field. We
      imposed no language restrictions. SELECTION CRITERIA: We included randomised or
      quasi-randomised controlled trials of ES with non-implanted devices compared with
      any other treatment for OAB in adults. Eligible trials included adults with OAB
      with or without urgency urinary incontinence (UUI). Trials whose participants had
      stress urinary incontinence (SUI) were excluded. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened search results, extracted data from
      eligible trials and assessed risk of bias, using the Cochrane Collaboration's
      'Risk of bias' tool. MAIN RESULTS: We identified 51 eligible trials (3443
      randomised participants). Thirty-three trials did not report the primary outcomes
      of subjective change in OAB symptoms. The majority of trials were deemed to be at
      low or unclear risk of selection and attrition bias and unclear risk of
      performance and detection bias. Lack of clarity with regard to risk of bias was
      largely due to poor reporting.Twenty-three trials (1654 participants) compared ES
      with no active treatment, placebo or sham treatment. Moderate-quality evidence
      indicated that OAB symptoms were more likely to improve in people receiving ES
      than with no active treatment, placebo or sham treatment (relative risk (RR) for
      no improvement 0.54, 95% confidence interval (CI) 0.47 to 0.63). Moderate-quality
      evidence indicated that similar numbers of people receiving ES and no active
      treatment, placebo or sham treatment experienced adverse effects.Eight trials
      (542 participants) compared ES with conservative treatment. Very low-quality
      evidence suggested no evidence of a difference between ES and PFMT or PFMT plus
      biofeedback in OAB symptoms (RR for no improvement 0.79, 95% CI 0.51 to 1.21 and
      0.97, 95% CI 0.60 to 1.57 respectively). There was no evidence of a difference
      between ES and conservative treatment with regard to adverse effects.Sixteen
      trials (894 participants) compared ES with drug treatment (probanthine,
      tolterodine, oxybutynin, propantheline bromide, solifenacin succinate,
      terodiline, trospium chloride, terodiline). Moderate-quality evidence indicated
      that OAB symptoms were more likely to improve with ES than drug treatment (RR for
      no improvement 0.66, 95% CI 0.48 to 0.90). Low-quality evidence suggested a
      greater risk of adverse effects with oxybutynin (RR 1.26, 95% CI 1.07 to 1.49)
      and with tolterodine (RR 1.51, 95% CI 1.21 to 1.89) than with ES. There was
      insufficient evidence of a difference between ES and trospium hydrochloride (RR
      0.73, 95% CI 0.43 to 1.25).Eight trials (252 participants) compared ES combined
      with another treatment versus the other treatment alone, two trials (48
      participants) compared ES plus conservative treatment with no active treatment,
      placebo or sham treatment and six trials (361 participants) compared different
      types of ES. None of these comparisons had sufficient evidence to indicate any
      differences between the treatment groups in terms of OAB or adverse
      effects.Moderate-quality evidence suggested that ES improved OAB-related quality
      of life more than no active treatment, placebo or sham treatment. There was
      insufficient evidence of any difference between ES and any other treatment with
      regard to quality of life.There was insufficient evidence to determine if the
      benefits of ES persisted after the active treatment period stopped. AUTHORS'
      CONCLUSIONS: Electrical stimulation appeared to be more effective than both no
      treatment and drug treatment for OAB. There was insufficient evidence to
      determine if ES was more effective than conservative treatment or which type of
      ES was more effective. This review underlines the need to conduct well-designed
      trials in this field measuring subjective outcomes and adverse effects.

PMID- 27037010
TI  - Morphology of the distal thoracic duct and the right lymphatic duct in different
      head and neck pathologies: an imaging based study.
AB  - BACKGROUND: The purpose of this study was to assess the influence of head and
      neck pathologies on the detection rate, configuration and diameter of the
      thoracic duct (TD) and right lymphatic duct (RLD) in computed tomography (CT) of
      the head and neck. METHODS: One hundred ninety-seven patients were divided into
      the subgroups "healthy", "benign disease" and "malignant disease". The
      interpretation of the images was performed at a slice thickness of 3 mm in the
      axial and coronal plane. In each case we looked for the distal part of the TD and
      RLD respectively and subsequently evaluated their configuration (tubular,
      sacciform, dendritic) as well as their maximum diameter and correlated the
      results with age, gender and diagnosis group. RESULTS: The detection rate in the
      study population was 81.2 % for the TD and 64.2 % for the RLD and did not differ
      significantly in any of the subgroups. The predominant configuration was tubular.
      The configuration distribution did not differ significantly between the diagnosis
      groups. The mean diameter of the TD was 4.79 +/- 2.41 mm and that of the RLD was
      3.98 +/- 1.96 mm. No significant influence of a diagnosis on the diameter could
      be determined. CONCLUSIONS: There is no significant influence of head/neck
      pathologies on the CT detection rate, morphology or size of the TD and RLD.
      However our study emphasizes that both the RLD and the TD are detectable in the
      majority of routine head and neck CTs and therefore reading physicians and
      radiologists should be familiar with their various imaging appearances.

PMID- 27037011
TI  - Fetal gender is not associated with either gestational diabetes mellitus or
      placental weight: A cohort study.
AB  - AIM: This study assessed whether male fetal gender increases the risk of maternal
      gestational diabetes mellitus (GDM) and investigated the association with
      placental weight. METHODS: The study included 20,149 women without pregestational
      diabetes who delivered singletons at our hospital between January 2002 and
      December 2010. There was universal screening for GDM, and all placentas were
      weighed at delivery. RESULTS: GDM (affecting 14.2% of women) was not associated
      with fetal gender (male fetuses in women without and with GDM: 51.8% vs. 51.7%,
      respectively; P=0.957), and remained likewise after logistic-regression analysis
      of risk factors for GDM (OR: 1.007, 95% CI: 0.930-1.091; P=0.858). Placental
      weights were 600+/-126g, 596+/-123g, 584+/-118g and 587+/-181g in women with
      GDM/female, GDM/male, no GDM/female and no GDM/male fetuses, respectively (GDM
      effect: P=0.017; gender effect: P=0.41; GDM * gender effect: P=0.16). CONCLUSION:
      The present results suggest that fetal gender is not associated with GDM and,
      while placental weights were higher in cases of GDM, there were still no gender
      effects.

PMID- 27037012
TI  - Glycaemia and autistic traits in very low birth weight infants in adulthood.

PMID- 27037014
TI  - Virus-Like Particles Displaying Recombinant Short-Chain Fragment Region and
      Interleukin 2 for Targeting Colon Cancer Tumors and Attracting Macrophages.
AB  - Functionalized virus-like particles (VLPs) can target with specificity as drug
      delivery systems and can attract macrophages for the destruction of cancer cells.
      Here, the group antigen capsid protein from the Rous sarcoma virus was used to
      prepare VLPs, functionalized by displaying glycol-inositol phosphate-anchored
      recombinant single chain fragment variable (rscFv) and hemagglutinin
      transmembrane region anchored recombinant human interleukin-2 (rhIL2) (designated
      as VLP-rscFv-rhIL2s) in silkworms. The rscFv specifically binds the tumor
      associated glycoprotein 72 that is expressed at the surface of colon cancer
      cells. VLP-rscFv-rhIL2 was affinity purified and had a smooth particle size with
      a diameter of 50 nm. Calcein-AM-packaged VLP-rscFv-rhIL2s successfully targeted
      cancer cells as a model for drug delivery system. VLP-rscFv-rhIL2 bound with
      colon cancer cells that attracted macrophages (human monocytic cell line-1 cells)
      in chemotaxis chamber assays compared with negative controls. The macrophages
      secreted tumor necrosis factor-alpha, a cytokine that is necessary to destroy
      cancer cells. These results demonstrate the potential of VLP-rscFv-rhIL2 as an
      intelligent nano biomaterial that is capable of attracting macrophages.

PMID- 27037013
TI  - Nucleic acids delivery methods for genome editing in zygotes and embryos: the
      old, the new, and the old-new.
AB  - In the recent years, sequence-specific nucleases such as ZFNs, TALENs, and
      CRISPR/Cas9 have revolutionzed the fields of animal genome editing and
      transgenesis. However, these new techniques require microinjection to deliver
      nucleic acids into embryos to generate gene-modified animals. Microinjection is a
      delicate procedure that requires sophisticated equipment and highly trained and
      experienced technicians. Though over a dozen alternate approaches for nucleic
      acid delivery into embryos were attempted during the pre-CRISPR era, none of them
      became routinely used as microinjection. The addition of CRISPR/Cas9 to the
      genome editing toolbox has propelled the search for novel delivery approaches
      that can obviate the need for microinjection. Indeed, some groups have recently
      developed electroporation-based methods that have the potential to radically
      change animal transgenesis. This review provides an overview of the old and new
      delivery methods, and discusses various strategies that were attempted during the
      last three decades. In addition, several of the methods are re-evaluated with
      respect to their suitability to deliver genome editing components, particularly
      CRISPR/Cas9, to embryos.

PMID- 27037015
TI  - The relationship between central and peripheral oxytocin concentrations: a
      systematic review and meta-analysis protocol.
AB  - BACKGROUND: Research examining the effects of oxytocin (OT) interventions on
      psychiatric, social-behavioral, and social-cognitive outcomes regularly collect
      peripheral levels of OT as markers of central bioavailability. Such inferences
      rest on the assumption that central and peripheral levels of OT are directly
      associated. However, conflicting evidence from coordinated sampling of central
      and peripheral OT question the validity of this assumption. The purpose of this
      meta-analysis is to evaluate the correlation between central and peripheral OT,
      as well as to account for potential heterogeneity in the literature.
      METHODS/DESIGN: Studies that report coordinated sampling of central and
      peripheral OT in humans and animals will be identified. Research investigating
      concentrations in both basal states and after exogenous administration will be
      considered. PubMed and Embase databases will be searched, along with citation
      lists of retrieved articles. Peer-reviewed studies written in English published
      from 1971 onwards will be included in the meta-analysis. Data will be extracted
      from eligible studies for a random-effects meta-analysis. For each study, a
      summary effect size, heterogeneity, risk of bias, publication bias, and the
      effect of categorical and continuous moderator variables will be determined.
      DISCUSSION: This systematic review and meta-analysis will identify and synthesize
      evidence to determine if there is an association between central and peripheral
      OT concentrations. If significant associations are observed, evidence would
      provide a rationale for future research to use peripheral measures as a proxy for
      central OT concentrations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42015027864.

PMID- 27037016
TI  - A prospective cohort study of 14-3-3eta in ACPA and/or RF-positive patients with
      arthralgia.
AB  - BACKGROUND: 14-3-3eta (eta) is a novel serum/plasma protein biomarker involved in
      the upregulation of inflammatory and joint damage factors. We analysed the
      association of 14-3-3eta with the development of clinically apparent arthritis in
      a cohort of subjects with arthralgia and positivity for at least one serologic
      marker: rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA).
      METHODS: Measurement of 14-3-3eta in plasma collected on entry into the cohort.
      For this study, 144 subjects with a minimum of 2.5 (median and maximum 5) years
      of follow-up were available. The relationship between presence and levels of 14-3
      3eta and development of arthritis was investigated. RESULTS: Arthritis occurred
      in 43 (30 %) of the 144 subjects after a median of 15 months. 14-3-3eta was
      detectable up to 5 years before onset of clinical arthritis and was present
      significantly more often (36 % versus 14 %; relative risk 2.5, 95 % confidence
      interval 1.2-5.6; p = 0.02) and at significantly higher levels (median 0.95
      versus 0.28 ng/ml; p = 0.02) in subjects developing arthritis compared with those
      who did not. 14-3-3eta levels/positivity and ACPA, but not RF, were univariately
      associated with the development of arthritis while generalized linear model
      analysis with RF and ACPA as obligatory factors could not return an incremental
      benefit with 14-3-3eta. CONCLUSIONS: 14-3-3eta was detectable prior to the onset
      of arthritis and was associated with arthritis development in arthralgia subjects
      pre-selected for positivity of RF or ACPA. Its power to predict onset of
      arthritis independent of ACPA and RF requires a new study in which patients are
      not pre-selected based on ACPA and/or RF seropositivity.

PMID- 27037017
TI  - The unresolved mystery of high-density lipoprotein: time for a paradigm shift?

PMID- 27037018
TI  - Combined pressure and temperature denaturation of ribonuclease A produces
      alternate denatured states.
AB  - Protein folding, unfolding and misfolding have become critically important to a
      range of health and industry applications. Increasing high temperature and high
      pressure are used to control and speed up reactions. A number of studies have
      indicated that these parameters can have a large effecton protein structure and
      function. Here we describe the additive effects of these parameters on the small
      angle scattering behaviour of ribonuclease A. We find that alternate unfolded
      structures can be obtained with combined high pressure and temperature treatment
      of the protein.

PMID- 27037019
TI  - Edaravone suppresses degradation of type II collagen.
AB  - Osteoarthritis (OA) is a degenerative joint disease affecting millions of people.
      The degradation and loss of type II collagen induced by proinflammatory cytokines
      secreted by chondrocytes, such as factor-alpha (TNF-alpha) is an important
      pathological mechanism to the progression of OA. Edaravone is a potent free
      radical scavenger, which has been clinically used to treat the neuronal damage
      following acute ischemic stroke. However, whether Edaravone has a protective
      effect in articular cartilage hasn't been reported before. In this study, we
      investigated the chondrocyte protective effects of Edaravone on TNF-alpha induced
      degradation of type II collagen. And our results indicated that TNF-alpha
      treatment resulted in degradation of type II collagen, which can be ameliorated
      by treatment with Edaravone in a dose dependent manner. Notably, it was found
      that the inhibitory effects of Edaravone on TNF-alpha-induced reduction of type
      II collagen were mediated by MMP-3 and MMP-13. Mechanistically, we found that
      Edaravone alleviated TNF-alpha induced activation of STAT1 and expression of IRF
      1. These findings suggest a potential protective effect of Edaravone in OA.

PMID- 27037020
TI  - Aggravation of brain infarction through an increase in acrolein production and a
      decrease in glutathione with aging.
AB  - We previously reported that tissue damage during brain infarction was mainly
      caused by inactivation of proteins by acrolein. This time, it was tested why
      brain infarction increases in parallel with aging. A mouse model of
      photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old
      female C57BL/6 mice. The size of brain infarction in the mouse PIT model
      increased with aging. The volume of brain infarction in 12 month-old mice was
      approximately 2-fold larger than that in 2 month-old mice. The larger brain
      infarction in 12 month-old mice was due to an increase in acrolein based on an
      increase in the activity of spermine oxidase, together with a decrease in
      glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the
      decrease in one of the subunits of glutathione biosynthesizing enzymes, gamma
      glutamylcysteine ligase modifier subunit, with aging. The results indicate that
      aggravation of brain infarction with aging was mainly due to the increase in
      acrolein production and the decrease in GSH in brain. 

PMID- 27037021
TI  - Identification of baicalein as a ferroptosis inhibitor by natural product library
      screening.
AB  - Ferroptosis, a novel form of regulated cell death, is characterized by oxidative
      injury from iron accumulation and lipid peroxidation. In a natural product
      library screening for ferroptosis inhibitor, we found that baicalein is a potent
      inhibitor of erastin-induced ferroptosis in pancreatic cancer cells. Baicalein
      (also termed 5,6,7-trihydroxyflavone) is a flavonoid originally obtained from the
      roots of Scutellaria baicalensis and Scutellaria lateriflora. We showed that
      baicalein exhibits remarkable anti-ferroptosis activity compared with well-known
      ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, deferoxamine
      mesylate, and beta-mercaptoethanol. At the biochemistry level, baicalein limits
      erastin-induced ferrous iron production, glutathione depletion, and lipid
      peroxidation. At the protein level, baicalein suppresses erastin-mediated
      degradation of glutathione peroxidase 4, a phospholipid hydroperoxidase that
      protects cells against membrane lipid peroxidation. Thus, baicalein enhances
      cellular anti-ferroptosis capacity and could be a potential therapeutic agent for
      ferroptosis-associated tissue injury.

PMID- 27037022
TI  - Wound healing delays in alpha-Klotho-deficient mice that have skin appearance
      similar to that in aged humans - Study of delayed wound healing mechanism.
AB  - Skin atrophy and delayed wound healing are observed in aged humans; however, the
      molecular mechanism are still elusive. The aim of this study was to analyze the
      molecular mechanisms of delayed wound healing by aging using alpha-Klotho
      deficient (kl/kl) mice, which have phenotypes similar to those of aged humans.
      The kl/kl mice showed delayed wound healing and impaired granulation formation
      compared with those in wild-type (WT) mice. The skin graft experiments revealed
      that delayed wound healing depends on humoral factors, but not on kl/kl skin
      tissue. The mRNA expression levels of cytokines related to acute inflammation
      including IL-1beta, IL-6 and TNF-alpha were higher in wound lesions of kl/kl mice
      compared with the levels in WT mice by RT-PCR analysis. LPS-induced TNF-alpha
      production model using spleen cells revealed that TNF-alpha production was
      significantly increased in the presence of FGF23. Thus, higher levels of FGF23 in
      kl/kl mouse may have a role to increase TNF-alpha production in would lesion
      independently of alpha-Klotho protein, and impair granulation formation and delay
      wound healing.

PMID- 27037023
TI  - Sequential hydroxylation of vitamin D2 by a genetically engineered CYP105A1.
AB  - Our previous studies revealed that the double variants of CYP105A1- R73A/R84A and
      R73V/R84A-show high levels of activity with respect to conversion of vitamin D3
      to its biologically active form, 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2D3). In this study, we found that both the double variants were
      also capable of converting vitamin D2 to its active form, that is, 1alpha,25
      dihydroxyvitamin D2 (1alpha,25(OH)2D2), via 25(OH)D2, whereas its 1alpha
      hydroxylation activity toward 25(OH)D2 was much lower than that toward 25(OH)D3.
      Comparison of the wild type and the double variants revealed that the amino acid
      substitutions remarkably enhanced both 25- and 26-hydroxylation activity toward
      vitamin D2. After 25-hydroxylation of vitamin D2, further hydroxylation at C26
      may occur frequently without the release of 25(OH)D2 from the substrate-binding
      pocket. Thus, the double variants of CYP105A1 are quite useful to produce
      25,26(OH)2D2 that is one of the metabolites of vitamin D2 detected in human
      serum.

PMID- 27037024
TI  - Conformation switching of AIM2 PYD domain revealed by NMR relaxation and MD
      simulation.
AB  - Protein absent in melanoma 2 (AIM2) is a double-strand DNA (ds DNA) sensor mainly
      located in cytoplasm of cell. It includes one N terminal PYD domain and one C
      terminal HIN domain. When the ds DNA such as DNA viruses and bacteria entered
      cytoplasm, the HIN domain of AIM2 will recognize and bind to DNA, and the PYD
      domain will bind to ASC protein which will result in the formation of AIM2
      inflammasome. Three AIM2 PYD domain structures have been solved, but every
      structure yields a unique conformation around the alpha3 helix region. To
      understand why different AIM2 PYD structures show different conformations in this
      region, we use NMR relaxation techniques to study the backbone dynamics of mouse
      AIM2 PYD domain and perform molecular dynamics (MD) simulations on both mouse and
      human AIM2 PYD structures. Our results indicate that this region is highly
      flexible in both mouse and human AIM2 PYD domains, and the PYD domain may exist
      as a conformation ensemble in solution. Different environment makes the
      population vary among pre-existing conformational substrates of the ensemble,
      which may be the reason why different AIM2 PYD structures were observed under
      different conditions. Further docking analysis reveals that the conformation
      switching may be important for the autoinhibition of the AIM2 protein. 

PMID- 27037025
TI  - The CCR4-NOT deadenylase activity contributes to generation of induced
      pluripotent stem cells.
AB  - Somatic cells can be reprogrammed as induced pluripotent stem cells (iPSCs) by
      introduction of the transcription factors, OCT3/4, KLF4, SOX2, and c-MYC. The
      CCR4-NOT complex is the major deadenylase in eukaryotes. Its subunits Cnot1,
      Cnot2, and Cnot3 maintain pluripotency and self-renewal of mouse and human
      embryonic stem (ES) cells and contribute to the transition from partial to full
      iPSCs. However, little is known about how the CCR4-NOT complex post
      transcriptionally regulates the reprogramming process. Here, we show that the
      CCR4-NOT deadenylase subunits Cnot6, Cnot6l, Cnot7, and Cnot8, participate in
      regulating iPSC generation. Cnot1 knockdown suppresses expression levels of
      Cnot6, Cnot6l, Cnot7, and Cnot8 in mouse embryonic fibroblasts (MEFs) and
      decreases the number of alkaline phosphatase (ALP)-positive colonies after iPSC
      induction. Intriguingly, Cnot1 depletion allows Eomes and p21 mRNAs to persist,
      increasing their expression levels. Both mRNAs have longer poly(A) tails in Cnot1
      depleted cells. Conversely, forced expression of a combination of Cnot6, Cnot6l,
      Cnot7, and Cnot8 increases the number of ALP-positive colonies after iPSC
      induction and decreases expression levels of Eomes and p21 mRNAs. Based on these
      observations, we propose that the CCR4-NOT deadenylase activity contributes to
      iPSC induction.

PMID- 27037026
TI  - Injuries caused by fragmenting rifle ammunition.
AB  - INTRODUCTION: Although penetrating injuries are encountered on a regular basis in
      high volume trauma centres, most civilian trauma teams will be unfamiliar with
      the treatment of patients with injuries caused by fragmenting ammunition. The
      terrorist attacks in Norway on July 22, 2011 included a shooting spree causing 69
      deaths and 60 injured. One of the weapons used was a semi-automatic rifle,
      calibre 5.56mm, with soft tip, short stop ammunition. The aim of the present
      study was to describe the characteristic injury patterns and lessons learned from
      the treatment of multiple patients admitted at the regional trauma centre with
      injuries from this type of ammunition. METHODS: We undertook an observational
      study of patients admitted at Oslo University Hospital, Ulleval after the
      shooting spree at Utoya on July 22, 2011. Data on demographics, injuries, injury
      severity, surgical procedures and outcome were collected prospectively. RESULTS:
      Of the 21 patients admitted after the shooting incident, 18 were identified with
      injuries caused by fragmenting ammunition and included in the study. Median age
      was 17 years (IQR 16, 19), median ISS 21 (IQR 12, 30) and 12 patients were
      female. They had been hit by a total of 38 projectiles, of which 32 were
      fragmenting bullets. Of the seven patients who sustained injuries to the head,
      neck and face, one patient required a craniotomy and one patient had a non
      survivable head injury. Of the 11 patients with torso injuries, six of the eight
      patients with chest injuries had intra-thoracic injuries that could be treated
      with chest tubes only. One patient had cardiac tamponade, requiring thoracotomy.
      Six patients underwent laparotomy, four of them more than one. Of the 10 patients
      with extremity injuries, two had nerve injuries and six patients had fractures.
      Five amputations were performed within the first nine days. A total of 101
      operations were required within the first four weeks. The majority of these were
      repeated soft tissue debridements due to progressive necrosis. CONCLUSION:
      Knowledge about the specific challenges created by the progressive soft tissue
      necrosis caused by fragmenting ammunition should lead to planned, repeated
      debridements to reduce total tissue loss and complications.

PMID- 27037027
TI  - Improving core surgical training in a major trauma centre.
AB  - INTRODUCTION: English Major Trauma Centres (MTCs) were established in April 2012.
      Increased case volume and complexity has influenced trauma and orthopaedic (T&O)
      core surgical training in these centres. OBJECTIVES: To determine if T&O core
      surgical training in MTCs meets Joint Committee on Surgical Training (JCST)
      quality indicators including performance of T&O operative procedures and
      consultant supervised session attendance. METHODS: An audit cycle assessing the
      impact of a weekly departmental core surgical trainee rota. The rota included
      allocated timetabled sessions that optimised clinical and surgical learning
      opportunities. Intercollegiate Surgical Curriculum Programme (ISCP) records for
      T&O core surgical trainees at a single MTC were analysed for 8 months pre and
      post rota introduction. Outcome measures were electronic surgical logbook
      evidence of leading T&O operative procedures and consultant validated work-based
      assessments (WBAs). RESULTS: Nine core surgical trainees completed a 4 month MTC
      placement pre and post introduction of the core surgical trainee rota.
      Introduction of core surgical trainee rota significantly increased the mean
      number of T&O operative procedures led by a core surgical trainee during a 4
      month MTC placement from 20.2 to 34.0 (p<0.05). The mean number of hip
      hemiarthroplasty procedures led by a core surgical trainee during a 4 month MTC
      placement was significantly increased (0.3 vs 2.4 [p=0.04]). Those of dynamic hip
      screw fixation (2.3 vs 3.6) and ankle fracture fixation (0.7 vs 1.6) were not.
      Introduction of a core surgical trainee rota significantly increased the mean
      number of consultant validated WBAs completed by a core surgical trainee during a
      4 month MTC placement from 1.7 to 6.6 (p<0.0001). CONCLUSIONS: Introduction of a
      departmental core surgical trainee rota utilising a 'problem-based' model can
      significantly improve T&O core surgical training in MTCs.

PMID- 27037028
TI  - Moore I postero-medial articular tibial fracture in alpine skiers: Surgical
      management and return to sports activity.
AB  - PURPOSE: Over the past 10 years, like many authors, we observed an increasing
      number of Moore I tibial plateau fractures related to alpine skiing for which the
      surgeon may face difficult choices regarding surgical approach and fixation
      means. Some authors have recently been suggesting a posterior approach associated
      to open reduction and osteosynthesis by a buttress plate. But in our knowledge
      there is no specific study on sports activity recovery after Moore I tibial
      fractures. The aim of this work was to assess sports activities and clinical
      outcomes after surgically treated Moore I tibial plateau fractures in an athletic
      population of skiers. METHODS: We conducted a prospective case series between
      2012 and 2014. This included fifteen patients aged 39.6+/-7 years whom presented
      with a Moore I tibial plateau fracture during a skiing accident. 12 cases (80%)
      presented with an associated tibial spine fracture. Treatment consisted of a
      standard antero-medial approach, with a medial para patellar arthrotomy to allow
      direct visualisation of articular reduction and spinal fixation. Two or three
      6.5mm long cancellous bone screws were placed antero-posteriorly so as to ensure
      perfect compression of the fracture site. Radiological and functional results
      were assessed by an independent observer (Lysholm-Tegner, UCLA, KOOS scores) at
      the longest follow-up. RESULTS: Mean follow-up was 18.2+/-6 months (12-28). An
      immediate postoperative anatomical reduction was achieved in all cases and
      remained stable in time. At last follow-up Lysholm mean score was 85+/-14 points
      (59-100), UCLA score was 7.3+/-1.6 (4-10) and Tegner score was 4.6+/-1.3 (3-6).
      Mean KOOS score was 77+/-15 (54-97). 87% of patients had resumed their skiing
      activity and 93% were satisfied or very satisfied from their post-operative
      surgical outcome. We observed no pseudarthrosis or secondary varus displacement.
      CONCLUSION: In our series 87% of patients had resumed back to their sporting
      activities. Surgical management of Moore I tibial plateau fractures by isolated
      antero-posterior screwing provides excellent clinical and radiological results.
      The anteromedial incision has a dual advantage of anatomical reduction, tibial
      spine fixation (in 80% of our cases) and posteromedial fragment reduction.

PMID- 27037029
TI  - [Sun exposure at school: Evaluation of risk (erythema dose), benefits (vitamin-D
      synthesis) and behaviour among children in France].
AB  - BACKGROUND: To better understand the potential risk associated with sun exposure
      during the school year, we decided to evaluate behaviour, risk [UV index (UVI),
      minimal erythema dose (MED)] and benefits (vitamin-D synthesis) of sun exposure
      in primary schoolchildren in France, as well as the various sun protection
      methods used for children. MATERIAL AND METHODS: We performed the study on a
      sunny day (July 24) in a school in Antony (France). Evaluation of UVI (with
      calculation of MED) and the amount of vitamin D synthesized according to exposed
      body surface area and phototype were performed every 15minutes from 9 a.m. to 5
      p.m. The effects of albedo and shade on UVI were assessed in 8 different
      locations at the school. The sun-protection measures used by the children were
      systematically evaluated. RESULTS: Fifty-seven children were evaluated; the
      maximum UVI was 7.2 and the maximum temperature was 30.7 degrees C. Irrespective
      of phototype and clothing, 1 MED was reached and an adequate level of vitamin D
      was synthesized in the skin before midday. Albedo had little impact on
      irradiation. The amount of protection afforded by shadow varied greatly, with the
      highest level occurring in the covered courtyard (99.5% reduction of UVI) and the
      lowest in the shadow of buildings (53.7% reduction of UVI). With strict sun
      protection measures concerning dress, children reached 1 MED before synthesizing
      1000IU of vitamin D, but with clothing "suited to high temperatures", 1000IU of
      vitamin D were synthetized before 1 MED was reached. Compliance with
      photoprotection measures was poor. Regardless of duration of exposure during the
      day (minimal model: two play breaks+lunchtime break) and of skin phototype, at
      least 1.5 MED was reached during the day. STUDY LIMITATIONS: This was an
      experimental study ignoring children's actual behaviour (movement, sweating,
      application of sun protection products, etc.). Moreover, due to weather
      conditions, the study was performed at a recreation centre in July and not during
      the "standard" school year. CONCLUSION: Sun protection campaigns should naturally
      be directed chiefly towards children for several reasons relating to solar risk
      and learning. This study shows the complex link between UV, MED, vitamin D as
      well as the difficulties of implementing solar protection measures in schools in
      France.

PMID- 27037030
TI  - Long-term outcomes and healthcare utilization following critical illness--a
      population-based study.
AB  - BACKGROUND: The purpose of this study was to examine hospital mortality, long
      term mortality, and health service utilization among critically ill patients. We
      also determined whether these outcomes differed according to demographic and
      clinical characteristics. METHODS: We conducted a retrospective cohort study of
      adults (age >= 18 years) who survived admission to an intensive care unit (ICU)
      in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated
      admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac
      surgery ICUs. Adults (age >= 18 years) who survived an acute hospitalization that
      did not include an ICU stay formed the comparator group. The primary outcome was
      mortality following hospital discharge. Secondary outcomes were healthcare
      utilization, including emergency room admissions and hospital readmissions during
      follow-up. RESULTS: Over the study interval, 500,124 patients were admitted to
      ICUs and 420,187 (84%) survived to hospital discharge. Median follow-up for
      survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an
      ICU were more likely to subsequently visit the emergency department, be
      readmitted to the hospital and ICU, receive home care support, require
      rehabilitation, and be admitted for long-term care. Those requiring more
      resources within the ICU required more resources after discharge. One-third of
      patients admitted to the ICU died during long-term follow-up, with overall
      probabilities of death of 11% and 29% at 1 year and 5 years, respectively. In the
      adjusted analysis, there was an increasing hazard of death with increasing age,
      reaching a hazard ratio of 18.08 (95 % confidence interval 16.60-19.68) for those
      >= 85 years of age compared with those aged 18-24 years. CONCLUSIONS: Healthcare
      utilization after hospital discharge was higher among ICU patients, and also
      among those requiring more healthcare resources during their ICU admission, than
      among all hospitalized patients as a group. One-third of ICU patients died within
      the 5 years following discharge, and age was the most influential determinant of
      outcome. These findings should help target post-ICU discharge services for high
      risk groups and better inform goals-of-care discussions for elderly critically
      ill patients.

PMID- 27037032
TI  - The virome: a missing component of biological interaction networks in health and
      disease.
AB  - Host-associated viral populations, viromes, have been understudied relative to
      their contribution to human physiology. Viruses interact with host gene networks,
      influencing both health and disease. Analysis of host gene networks in the
      absence of virome analysis risks missing important network information. 

PMID- 27037033
TI  - Risk assessment and management of myocardial infarction.

PMID- 27037034
TI  - CardioPulse. Leaders in cardiovascular medicine today. Peter Libby MD.

PMID- 27037031
TI  - Systematic review: brain metastases from colorectal cancer--Incidence and patient
      characteristics.
AB  - BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are a rare event.
      However, the implications for affected patients are severe, and the incidence has
      been reported to be increasing. For clinicians, knowledge about the
      characteristics associated with BM is important and could lead to earlier
      diagnosis and improved survival. METHOD: In this paper, we describe the incidence
      as well as characteristics associated with BM based on a systematic review of the
      current literature, following the PRISMA guidelines. RESULTS: We show that the
      incidence of BM in CRC patients ranges from 0.6 to 3.2%. BM are a late stage
      phenomenon, and young age, rectal primary and lung metastases are associated with
      increased risk of developing BM. Molecular markers such as KRAS, BRAF, NRAS
      mutation as well as an increase in CEA and CA19.9 levels are suggested predictors
      of brain involvement. However, only KRAS mutations are reasonably well
      investigated and associated with an increased risk of BM. CONCLUSION: The
      incidence of BM from CRC is 0.6 to 3.2% and did not seem to increase over time.
      Development of BM is associated with young age, lung metastases, rectal primary
      and KRAS mutation. Increased awareness of brain involvement in patients with
      these characteristics is necessary.

PMID- 27037035
TI  - Accelerometry-enabled measurement of walking performance with a robotic
      exoskeleton: a pilot study.
AB  - BACKGROUND: Clinical scores for evaluating walking skills with lower limb
      exoskeletons are often based on a single variable, such as distance walked or
      speed, even in cases where a host of features are measured. We investigated how
      to combine multiple features such that the resulting score has high
      discriminatory power, in particular with few patients. A new score is introduced
      that allows quantifying the walking ability of patients with spinal cord injury
      when using a powered exoskeleton. METHODS: Four spinal cord injury patients were
      trained to walk over ground with the ReWalkTM exoskeleton. Body accelerations
      during use of the device were recorded by a wearable accelerometer and 4 features
      to evaluate walking skills were computed. The new score is the Gaussian naive
      Bayes surprise, which evaluates patients relative to the features' distribution
      measured in 7 expert users of the ReWalkTM. We compared our score based on all
      the features with a standard outcome measure, which is based on number of steps
      only. RESULTS: All 4 patients improved over the course of training, as their
      scores trended towards the expert users' scores. The combined score (Gaussian
      naive surprise) was considerably more discriminative than the one using only
      walked distance (steps). At the end of training, 3 out of 4 patients were
      significantly different from the experts, according to the combined score (p <
      .001, Wilcoxon Signed-Rank Test). In contrast, all but one patient were scored as
      experts when number of steps was the only feature. CONCLUSION: Integrating
      multiple features could provide a more robust metric to measure patients' skills
      while they learn to walk with a robotic exoskeleton. Testing this approach with
      other features and more subjects remains as future work.

PMID- 27037036
TI  - Genome-wide rare copy number variation screening in ulcerative colitis identifies
      potential susceptibility loci.
AB  - BACKGROUND: Ulcerative colitis (UC), a complex polygenic disorder, is one of the
      main subphenotypes of inflammatory bowel disease. A comprehensive dissection of
      the genetic etiology of UC needs to assess the contribution of rare genetic
      variants including copy number variations (CNVs) to disease risk. In this study,
      we performed a multi-step genome-wide case-control analysis to interrogate the
      presence of disease-relevant rare copy number variants. METHODS: One thousand one
      hundred twenty-one German UC patients and 1770 healthy controls were initially
      screened for rare deletions and duplications employing SNP-array data.
      Quantitative PCR and high density custom array-CGH were used for validation of
      identified CNVs and fine mapping. Two main follow-up panels consisted of an
      independent cohort of 451 cases and 1274 controls, in which CNVs were assayed
      through quantitative PCR, and a British cohort of 2396 cases versus 4886 controls
      with CNV genotypes based on array data. Additional sample sets were assessed for
      targeted and in silico replication. RESULTS: Twenty-four rare copy number
      variants (14 deletions and 10 duplications), overrepresented in UC patients were
      identified in the initial screening panel. Follow-up of these CNV regions in four
      independent case-control series as well as an additional public in silico control
      group (totaling 4439 UC patients and 15,961 healthy controls) revealed three copy
      number variants enriched in UC patients; a 15.8 kb deletion upstream of ABCC4 and
      CLDN10 at13q32.1 (0.43% cases, 0.11% controls), a 119 kb duplication at 7p22.1,
      overlapping RNF216, ZNF815, OCM and CCZ1 (0.13% cases, 0.01% controls) and a 134
      kb large duplication upstream of the KCNK9 gene at 8q24.3 (0.22% carriers among
      cases, 0.03% carriers among controls). The trend of association with UC was
      present after the P-values were corrected for combining data from different
      subpopulations. Break-point mapping of the deleted region suggested non-allelic
      homologous recombination as the mechanism underlying its formation. CONCLUSION:
      Our study presents a pragmatic approach for effective rare CNV screening of SNP
      array data sets and implicates the potential contribution of rare structural
      variants in the pathogenesis of UC.

PMID- 27037037
TI  - Coupling of an active middle-ear implant to the long process of the incus using
      an elastic clip attachment.
AB  - The active middle-ear implant Vibrant Soundbridge(c) (VSB) is used to treat mild
      to-severe sensorineural hearing losses. The standard surgical approach for incus
      vibroplasty is a mastoidectomy and a posterior tympanotomy, crimping the Floating
      Mass Transducer (FMT) to the long process of the incus (LPI) (standard crimped
      application). However, tight crimping increases the risk of necrosis of the LPI,
      resulting in reduction of energy transfer and loss of amplification. The aim of
      this study was to develop a new coupling device for the LPI, that does not
      require crimping, and to test its vibrational transfer properties in temporal
      bone preparations. An extended antrotomy and a posterior tympanotomy were
      performed in ten fresh human temporal bones. As a control for normal middle-ear
      function, the tympanic membrane was stimulated acoustically and the vibration of
      the stapes footplate was measured by laser Doppler vibrometry (LDV). FMT-induced
      vibration responses of the stapes were then measured for the standard crimped
      application at the LPI and for the newly designed elastic long process coupler
      (LP coupler). For the LP coupler, velocity-amplitude responses in temporal-bone
      preparations showed increased mean amplitudes at around 1 kHz (~10 dB) and a
      reduction between 1.8 and 6 kHz (13 dB on average for 2 <= f <= 5 kHz). In
      conclusion, attachment of the FMT to the LPI with the LP coupler leads to
      generally good mechanical and functional coupling in temporal-bone preparations
      with a notable disadvantage between 1.8 and 6 kHz. Due to its elastic clip
      attachment it is expected that the LP coupler will reduce the risk of necrosis of
      the incus long process, which has to been shown in further studies. Clinical
      results of the LP coupler are pending.

PMID- 27037038
TI  - Epistatic interactions between at least three loci determine the "rat-tail"
      phenotype in cattle.
AB  - BACKGROUND: The "rat-tail" syndrome (RTS) is an inherited hypotrichosis in
      cattle, which is exclusively expressed in diluted coloured hair. The affected
      animals also suffer from disturbed thermoregulation, which impairs their health
      and growth performance. Phenotypic features that are similar to RTS are observed
      in dogs with black hair follicle dysplasia. RESULTS: We used a resource cross
      population between German Holstein and Charolais cattle breeds to prove that
      epistatic interactions between at least three independent genetic loci are
      required for the expression of the RTS phenotype. In this population, the RTS is
      exclusively expressed in animals with a eumelanic background that is due to the
      dominant E (D) allele at the melanocortin 1 receptor gene located on Bos taurus
      autosome (BTA) 18. In addition, only the individuals that are heterozygous at the
      dilution locus on BTA5 that corresponds to the premelanosome protein or silver
      gene variant c.64G>A were classified as displaying a RTS phenotype. Linkage and
      whole-genome association analyses using different models and different pedigrees
      allowed us to map a third locus (hereafter referred to as the RTS locus) that is
      essential for the expression of the RTS phenotype to the chromosomal region
      between 14 and 22 Mb on BTA5. Our findings clearly demonstrate that the RTS and
      dilution loci are distinct loci on BTA5. CONCLUSIONS: Our study provides evidence
      that the RTS locus has effects on hair conformation and coat colour dilution and
      that the effect on coat colour dilution is clearly independent from that of the
      dilution locus. Finally, our results excluded several other loci that were
      previously reported to be associated with or to underlie hair conformation or
      pigmentation traits as the causal mutations of RTS and also several major
      functional candidate genes that are associated with hypotrichosis in humans. Our
      finding on the identification of a three-locus interaction that underlies RTS
      provides a prime example of epistatic interaction between several independent
      loci that is required for the expression of a distinct phenotype.

PMID- 27037039
TI  - Identification of differentially expressed plasma proteins in atherosclerotic
      patients with type 2 diabetes.
AB  - Besides hyperglycaemia and insulin resistance, several factors are associated
      with a higher cardiovascular risk in type 2 diabetes mellitus (T2DM), many of
      them being closely related to each other owing to common origins or pathways. The
      pathophysiological mechanisms underlying vascular dysfunctions in diabetes
      include reduced bioavailability of nitric oxide, increased ROS and prothrombotic
      factors production, as well as activation of receptors for advanced glycation end
      products. These alterations contribute to create a pro-inflammatory/thrombotic
      state that ultimately leads to plaque formation and complication. This study
      aimed at identifying differentially expressed plasma proteins between T2DM and
      non-diabetic patients undergoing carotid endarterectomy, by means of two
      dimensional electrophoresis coupled with LC-MS/MS. Before analysis, plasma
      samples were enriched in low-expression proteins through combinatorial
      hexapeptide ligand libraries. Both mono- and two-dimensional western blotting
      were performed for data validation. Differentially expressed proteins were mapped
      onto STRING v10 to build a protein-protein interaction network. Sixteen
      differentially expressed spots were identified with a high score. Among them,
      there were fibrinogen beta and gamma chains, complement C1r, C3 and C4-B
      subcomponents, alpha-1-antitrypsin (AAT), vitronectin and CD5 antigen-like.
      Protein-Protein interaction analysis evidenced a network among differentially
      expressed proteins in which vitronectin seems to represent a potentially pivotal
      node among fibrinolysis, complement dependent immune responses and inflammation
      in accordance with a number of in vitro and in vivo evidences for a contributory
      role of these proteins to the development of diabetic atherosclerosis.

PMID- 27037040
TI  - The role of the high-mobility group box1 protein-Toll like receptor pathway in
      diabetic vascular disease.
AB  - OBJECTIVES: Increased Toll like receptors (TLRs) especially 2 and 4 have been
      demonstrated in obesity, metabolic syndrome (MetS) and diabetes resulting in
      increased cellular inflammation. Since we have shown increased TLR2 and 4
      activities in both T1DM and T2DM and MetS, we wanted to elucidate the mechanisms
      of this sterile inflammation. In T1DM, T2DM and MetS we have shown that high
      mobility group box 1 protein (HMGB-1), a non-histone DNA binding protein is
      increased and could be a potential activator of TLRs since it has previously
      shown to activate TLR2, 4 and 9. We examined the role of HMGB-1 in patients and
      animal models of diabetes and MetS to determine how important it is as an
      activator of TLR mediated inflammation and its role in diabetic vascular
      complications. METHODS: A Medline search was conducted using the terms HMGB-1,
      TLRs and diabetes. RESULTS: HMGB-1 levels are increased in patients with diabetes
      and MetS, and associated with increased biomediators of inflammation. Furthermore
      data supported a role of HMGB-1 in both diabetic microvascular and macrovascular
      complications. CONCLUSIONS: HMGB-1 interaction with TLRs is implicated in
      diabetic complications and could be important therapeutic target.

PMID- 27037042
TI  - Decreased plasma alpha-Klotho predict progression of nephropathy with type 2
      diabetic patients.
AB  - AIM: The potential role of soluble alpha-klotho in diabetic kidney disease has
      not yet been evaluated. The aim of this study was to evaluate the association of
      plasma and/or urine alpha-klotho with the progression of type 2 diabetic
      nephropathy. METHODS: The baseline values of plasma and urine alpha-klotho were
      measured in 147 patients with type 2 diabetes mellitus with an estimated
      glomerular filtration rate (eGFR) of >=60mL/min/1.73m(2). In this prospective
      observational study, a total of 109 type 2 diabetic patients were followed up for
      34months (8-50 months). RESULTS: Plasma alpha-klotho, but not urine alpha-klotho,
      was negatively correlated with the decline of eGFR (r=-0.304, P=0.001; r=0.042,
      P=0.068, respectively). After adjusting for several clinical parameters, baseline
      eGFR and urine ACR, plasma alpha-klotho was significantly associated with the
      decline of eGFR (r=-0.219, P=0.008). In the normoalbuminuria group (n=63), the
      plasma alpha-klotho remained significantly associated with a decline in eGFR
      (r=0.324, P=0.004) in the final model. CONCLUSIONS: It is suggested that plasma
      alpha-klotho may be an early biomarker for predicting renal impairment in type 2
      diabetic patients. The disappearance of a compensatory increase of plasma alpha
      klotho might be a predictive marker for the progression of type 2 diabetic
      nephropathy.

PMID- 27037043
TI  - Enhancing duration processing with parietal brain stimulation.
AB  - Numerosity and duration are thought to share common magnitude-based mechanisms in
      brain regions including the right parietal and frontal cortices like the
      supplementary motor area, SMA. Numerosity and duration are, however, also
      different in several intrinsic features. For instance, in a quantification
      context, numerosity is known for being more automatically accessed than temporal
      events, and durations are by definition sequential whereas numerosity can be both
      sequential and simultaneous. Moreover, numerosity and duration processing diverge
      in terms of their neuronal correlates. Whether these observed neuronal
      specificities can be accounted for by differences in automaticity or presentation
      mode is however not clear. To address this issue, we used brain stimulation
      (transcranial random noise stimulation, tRNS) to the right parietal cortex or the
      SMA combined with experimental stimuli differing in their level of automaticity
      (numerosity and duration) and presentation mode (sequential or simultaneous).
      Compared to a no stimulation group, performance changed in duration but not in
      numerosity categorisation following right parietal but not SMA stimulation. These
      results indicate that the right parietal cortex is critical for duration
      processing, and suggest that tRNS has a stronger effect on less automatic
      processes such as duration.

PMID- 27037041
TI  - Functional and morphological alterations of the urinary bladder in type 2
      diabetic FVB(db/db) mice.
AB  - AIMS: Diabetic bladder dysfunction (DBD) has been extensively studied in animal
      models of type 1 diabetes. We aimed to examine the functional and morphological
      alterations of the urinary bladder in a type 2 diabetes model, FVB(db/db) mice.
      METHODS: FVB(db/db) mice and age-matched FVB/NJ control mice were tested at
      either 12, 24 or 52weeks of age. Body weight, blood glucose and glycated
      hemoglobin (HbA1c) levels were measured. Bladder function was assessed by
      measurement of 24-h urination behavior and conscious cystometry. Bladder was
      harvested for Masson's Trichrome staining and morphometric analysis. RESULTS: The
      body weights of FVB(db/db) mice were twice as those of FVB/NJ control mice. The
      blood glucose and HbA1c levels were higher in FVB(db/db) mice at 12 and 24weeks,
      but not at 52weeks. A significant increase in the mean volume per void, but
      decrease in the voiding frequency, in FVB(db/db) mice was observed. Cystometry
      evaluation showed increased bladder capacity, voided volume, and peak micturition
      pressure in FVB(db/db) mice compared with FVB/NJ mice. Morphometric analysis
      revealed a significant increase in the areas of detrusor muscle and urothelium in
      FVB(db/db) mice. In addition, some FVB(db/db) mice, especially males at 12 and
      24weeks, showed small-volume voiding during 24-h urination behavior measurement,
      and detrusor overactivity in the cystometry measurement. CONCLUSIONS: The
      FVB(db/db) mouse, displaying DBD characterized by not only increased bladder
      capacity, void volume, and micturition pressure, but also bladder overactivity,
      is a useful model to further investigate the mechanisms of type 2 diabetes
      related bladder dysfunction.

PMID- 27037045
TI  - Aberrant Subclavian and Vertebrals Arteries in Acute Aortic Syndrome.

PMID- 27037044
TI  - Cognitive and connectome properties detectable through individual differences in
      graphomotor organization.
AB  - We investigated whether graphomotor organization during a digitized Clock Drawing
      Test (dCDT) would be associated with cognitive and/or brain structural
      differences detected with a tractography-derived structural connectome of the
      brain. 72 non-demented/non-depressed adults were categorized based on whether or
      not they used 'anchor' digits (i.e., 12, 3, 6, 9) before any other digits while
      completing dCDT instructions to "draw the face of a clock with all the numbers
      and set the hands to 10 after 11". 'Anchorers' were compared to 'non-anchorers'
      across dCDT, additional cognitive measures and connectome-based metrics. In the
      context of grossly intact clock drawings, anchorers required fewer strokes to
      complete the dCDT and outperformed non-anchorers on executive functioning and
      learning/memory/recognition tasks. Anchorers had higher local efficiency for the
      left medial orbitofrontal and transverse temporal cortices as well as the right
      rostral anterior cingulate and superior frontal gyrus versus non-anchorers
      suggesting better regional integration within local networks involving these
      regions; select aspects of which correlated with cognition. Results also revealed
      that anchorers' exhibited a higher degree of modular integration among
      heteromodal regions of the ventral visual processing stream versus non-anchorers.
      Thus, an easily observable graphomotor distinction was associated with 1) better
      performance in specific cognitive domains, 2) higher local efficiency suggesting
      better regional integration, and 3) more sophisticated modular integration
      involving the ventral ('what') visuospatial processing stream. Taken together,
      these results enhance our knowledge of the brain-behavior relationships
      underlying unprompted graphomotor organization during dCDT.

PMID- 27037046
TI  - Marfan Syndrome Caused by Somatic Mosaicism in an FBN1 Splicing Mutation.

PMID- 27037047
TI  - Lithium Use in Older Adults is Associated with Increased Prescribing of Parkinson
      Medications.
AB  - OBJECTIVE: To test the hypothesis of an increased incidence of antiparkinson drug
      prescribing or Parkinson disease (PD) diagnostic codes after chronic lithium
      treatment compared with chronic valproic acid or antidepressant treatment among
      older adults. METHODS: A retrospective cohort study using healthcare
      administrative databases in Ontario, Canada included 1,749 lithium users, 1,787
      valproic acid users, and 285,154 other antidepressant users >= 66 years old
      having used the drug continuously in monotherapy for at least 1 year. Outcome
      measures were start of (1) a dopaminergic medication (levodopa or a dopamine
      agonist), (2) any antiparkinson drug (levodopa, dopamine agonists,
      anticholinergic medication, amantadine, monoamine oxidase B inhibitors), (3) any
      antiparkinson drug or a diagnostic code for PD, and (4) any antiparkinson drug in
      the absence of a diagnostic code for PD. RESULTS: For patients with no previous
      antipsychotic use, lithium monotherapy was associated with an increased incidence
      of dopaminergic drug use (adjusted HR: 1.87; 95% CI: 1.06-3.30) and an increased
      incidence of antiparkinson drug use or a PD diagnosis (adjusted HR: 1. 68; 95%
      CI: 1.13-2.48) compared with antidepressant monotherapy. CONCLUSION: Chronic
      lithium use is associated with an increased incidence of dopaminergic drug use
      compared with antidepressants, identifying a prescribing cascade related to
      lithium use in the elderly. Whether this reflects inappropriate treatment of
      action tremor or treatment of drug-induced parkinsonism should be addressed by a
      close examination of prescribing practices.

PMID- 27037048
TI  - Authors' commentary: Impact of bronchoalveolar lavage multiplex PCR on
      microbiological yield and therapeutic decisions in severe pneumonia in ICU.

PMID- 27037049
TI  - Key stakeholders' perceptions of the acceptability and usefulness of a tablet
      based tool to improve communication and shared decision making in ICUs.
AB  - PURPOSE: Although barriers to shared decision making in intensive care units are
      well documented, there are currently no easily scaled interventions to overcome
      these problems. We sought to assess stakeholders' perceptions of the
      acceptability, usefulness, and design suggestions for a tablet-based tool to
      support communication and shared decision making in ICUs. METHODS: We conducted
      in-depth semi-structured interviews with 58 key stakeholders (30 surrogates and
      28 ICU care providers). Interviews explored stakeholders' perceptions about the
      acceptability of a tablet-based tool to support communication and shared decision
      making, including the usefulness of modules focused on orienting families to the
      ICU, educating them about the surrogate's role, completing a question prompt
      list, eliciting patient values, educating about treatment options, eliciting
      perceptions about prognosis, and providing psychosocial support resources. The
      interviewer also elicited stakeholders' design suggestions for such a tool. We
      used constant comparative methods to identify key themes that arose during the
      interviews. RESULTS: Overall, 95% (55/58) of participants perceived the proposed
      tool to be acceptable, with 98% (57/58) of interviewees finding six or more of
      the seven content domains acceptable. Stakeholders identified several potential
      benefits of the tool including that it would help families prepare for the
      surrogate role and for family meetings as well as give surrogates time and a
      framework to think about the patient's values and treatment options. Key design
      suggestions included: conceptualize the tool as a supplement to rather than a
      substitute for surrogate-clinician communication; make the tool flexible with
      respect to how, where, and when surrogates can access the tool; incorporate
      interactive exercises; use video and narration to minimize the cognitive load of
      the intervention; and build an extremely simple user interface to maximize
      usefulness for individuals with low computer literacy. CONCLUSION: There is broad
      support among stakeholders for the use of a tablet-based tool to improve
      communication and shared decision making in ICUs. Eliciting the perspectives of
      key stakeholders early in the design process yielded important insights to create
      a tool tailored to the needs of surrogates and care providers in ICUs.

PMID- 27037050
TI  - OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity:
      Findings From a Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - CONTEXT: Patients with post-stroke spasticity (PSS) commonly experience pain in
      affected limbs, which may impact quality of life. OBJECTIVES: To assess
      onabotulinumtoxinA for pain in patients with PSS from the BOTOX((r)) Economic
      Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled
      trial. METHODS: Patients with PSS (N = 273) were randomized to 22- to 34-week
      double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo
      injection + SC and were eligible to receive open-label onabotulinumtoxinA up to
      52 weeks. Assessments included change from baseline on the 11-point pain numeric
      rating scale, proportion of patients with baseline pain >=4 achieving >=30% and
      >=50% improvement in pain, and pain interference with work at Week 12, end of
      double-blind treatment, and Week 52. RESULTS: At baseline, most patients (74.3%)
      experienced pain and 47.4% had pain >=4 (pain subgroup). Mean pain reduction from
      baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (
      0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P <
      0.05). Higher proportions of patients in the pain subgroup achieved >=30% and
      >=50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and
      37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P <
      0.05). Reductions in pain were sustained through Week 52. Compared with placebo +
      SC, onabotulinumtoxinA consistently reduced pain interference with work.
      CONCLUSION: This is the first randomized, placebo-controlled trial demonstrating
      statistically significant and clinically meaningful reductions in pain and pain
      interference with work with onabotulinumtoxinA in patients with PSS.

PMID- 27037051
TI  - An overview on the delivery of antitumor drug doxorubicin by carrier proteins.
AB  - Serum proteins play an increasing role as drug carriers in the clinical settings.
      In this review, we have compared the binding modalities of anticancer drug
      doxorubicin (DOX) to three model carrier proteins, human serum albumin (HSA),
      bovine serum albumin (BSA) and milk beta-lactoglobulin (beta-LG) in order to
      determine the potential application of these model proteins in DOX delivery.
      Molecular modeling studies showed stronger binding of DOX with HSA than BSA and
      beta-LG with the free binding energies of -10.75 (DOX-HSA), -9.31 (DOX-BSA) and 
      8.12kcal/mol (DOX-beta-LG). Extensive H-boding network stabilizes DOX-protein
      conjugation and played a major role in drug-protein complex formation. DOX
      complexation induced major alterations of HSA and BSA conformations, while did
      not alter beta-LG secondary structure. The literature review shows that these
      proteins can potentially be used for delivery of DOX in vitro and in vivo. 

PMID- 27037052
TI  - Dextran-PLGA-loaded docetaxel micelles with enhanced cytotoxicity and better
      pharmacokinetic profile.
AB  - Docetaxel is one of the promising drugs and employed for the management of
      variety of cancers. However, challenges like poor-bioavailability, low tissue
      permeability, compromised aqueous solubility and dose-dependent side-effects
      limit its clinical applications. Whereas, PLGA-based polymeric micelles possess
      the ability to enhance the tissue permeability of drugs and increase their
      biocompatibility. Henceforth, it was aimed to fabricate the dextran-PLGA-based
      polymeric-micelles loaded with docetaxel to explore the potential benefits in
      drug delivery. Dextran was chemically linked to PLGA and the linkage was
      confirmed by FT-IR, UV and NMR-spectroscopy. Critical-micelle-concentration of
      amphiphilic polymer was determined and drug was encapsulated by diffusion
      technique and erythrocyte compatibility. The system was evaluated for drug
      release profile and in vitro cytotoxicity studies. The pharmacokinetic profile
      was studied in rats. The micelles obtained were of 96.5+/-2.5nm and offered drug
      encapsulation of order of 54.85+/-1.21%.The cytotoxicity of drug against MCF-7
      and MDA-MB-231 cell lines was enhanced by approx. 100%. The pharmacokinetic
      profile was substantially modified and about 16-folds enhancement in
      bioavailability was observed vis-a-vis plain drug. The approach was not only able
      to control the drug release, but also offered promise to enhance the
      pharmacokinetic and pharmacodynamic potential of docetaxel and similar anticancer
      agents. 

PMID- 27037053
TI  - Cellulose derivatives modified by sodium tellurate and a chromium(III) tellurate
      complex.
AB  - A novel cellulose (Cell) derivative, sodium-tellurato (Cell-TeO(OH)4(ONa)/Cell
      Cl), has been synthesized from the reaction of 6-chloro-6-deoxycellulose (Cell
      Cl) with telluric acid in the presence of sodium hydroxide. The subsequent
      reaction of this polymeric material with chromium(III) in aqueous solution yields
      the [Cr(Cell-TeO3(OH)3/Cell-Cl)(Cell-TeO2(OH)4/Cell-Cl)(H2O)3] complex. The
      molecular structures and morphology of the new polymer and the Cr(III) complex
      have been examined using elemental analysis, solid-state (13)C NMR, UV-vis, XRD
      and FTIR spectroscopy, and SEM-EDX, TGA and magnetic measurements. The results
      are considered to be consistent with the formulations proposed. The deprotonation
      constants of the modified cellulose and the stability constant of the Cr(III)
      complex have been determined by pH-metric measurements. 

PMID- 27037054
TI  - Immobilization of pectinase onto Fe3O4@SiO2-NH2 and its activity and stability.
AB  - Fe3O4 magnetic nanometer particles (MNPS) with a diameter of 30-40nm and coated
      by ammoniated silicon dioxides were developed by sol-gel method. The X-ray
      diffraction (XRD) pattern indicates that the Fe3O4 is wrapped in the amorphous
      SiO2, and the Fourier-transform infrared spectroscopy (FT-IR) analysis confirmed
      the NH2 group had been successfully introduced onto the surface of Fe3O4@SiO2
      nanoparticles. The main factors related to the immobilization process of
      pectinase onto the magnetic support were optimized by multi-factor orthogonal
      experiments, and the recommended combination is that 3% glutaraldehyde (coupling
      agent), pH=8.0, 50 degrees C, and cross-linking time 8h. Scanning electron
      microscope (SEM) and FT-IR analyses confirmed that the pectinase had been
      immobilized onto the surface of the amino modified nanoparticles. The storage
      stability and reusability of the pectinase were enhanced by the immobilization
      that 64.4% of the total starting activity was retrieved after 7 recycling batches
      and only about 21.1% of the total activity was lost after 30-day storage. For the
      application of the immobilized pectinase, the optimal pH and temperature were 8.5
      and 55 degrees C, respectively. 

PMID- 27037055
TI  - Comments on using of "pseudo-first-order model" in adsorption [Int. J. Biol.
      Macromol., vol. 81].

PMID- 27037056
TI  - Fabrication of porous gelatin-chitosan microcarriers and modeling of process
      parameters via the RSM method.
AB  - Porous gelatin-chitosan microcarriers (MCs) with the size of 350+/-50MUm were
      fabricated with blends of different gelatin/chitosan (G/C) weight ratio using an
      electrospraying technique. Response surface methodology (RSM) was used to study
      the quantitative influence of process parameters, including blend ratio, voltage,
      and syringe pump flow rate, on MCs diameter and density. In the following, MCs of
      the same diameter and different G/C weight ratio (1, 2, and 3) were fabricated
      and their porosity and biocompatibility were investigated via SEM images and MTT
      assay, respectively. The results showed that mesenchymal stem cells (MSCs) could
      attach, proliferate, and spread on fabricated porous MCs during 7 days of
      culturing especially on those prepared with a G/C weight ratio of 1. Such porous
      gelatin-chitosan MCs with a G/C weight ratio of 1 may be considered as a
      promising candidate for injectable carriers supporting attachment and
      proliferation of MSCs. 

PMID- 27037057
TI  - Understanding the impact of area-based interventions on area safety in deprived
      areas: realist evaluation of a neighbour nuisance intervention in Arnhem, the
      Netherlands.
AB  - BACKGROUND: Area-based health inequalities may partly be explained by higher
      levels of area disorder in deprived areas. Area disorder may cause safety
      concerns and hence impair health. This study assessed how, for whom and in what
      conditions the intervention Meeting for Care and Nuisance (MCN) had an impact on
      neighbour nuisance and area safety in four deprived districts in Arnhem, the
      Netherlands. METHODS: Realist evaluation methodology was applied to uncover how,
      for whom, and under what conditions MCN was expected to and actually produced
      change. Expected change was based on action plans and scientific theories. Actual
      change was based on progress reports, media articles, interviews with district
      managers, and quantitative surveys. RESULTS: Three levels of impact were
      distinguished. At the organisational level, partly as expected, MCN's coordinated
      partnership strategy enabled role alignment, communication, and leadership. This
      resulted in a more efficient approach of nuisance households. At the level of
      nuisance households, as expected, MCN's joint assistance and enforcement strategy
      removed many of the underlying reasons for nuisance. This resulted in less
      neighbour nuisance. At the district level, perceptions of social control and area
      safety improved only in one district. Key conditions for change included a wider
      safety approach, dense population, and central location of the district within
      the city. CONCLUSIONS: This realist evaluation provided insight into the
      mechanisms by which a complex area-based intervention was able to reduce
      neighbour nuisance in deprived areas. Depending on wider conditions, such a
      reduction in neighbour nuisance may or may not lead to improved perceptions of
      area safety at the district level.

PMID- 27037058
TI  - Systolic arterial blood pressure estimated by mitral regurgitation velocity, high
      definition oscillometry, and Doppler ultrasonography in dogs with naturally
      occurring degenerative mitral valve disease.
AB  - INTRODUCTION: To determine if systolic blood pressure estimated by mitral
      regurgitation (MR) velocity can be used interchangeably with that estimated by
      high definition oscillometry (HDO) and Doppler ultrasonography (DU) in dogs with
      naturally occurring mitral valve disease (MVD). ANIMALS: Forty-nine client-owned
      dogs with naturally occurring MVD. MATERIALS AND METHODS: This is a retrospective
      study. Medical records were reviewed and dogs with MR caused by degenerative MVD
      were included if systolic blood pressure was estimated from MR velocity
      determined by continuous wave Doppler (CW), DU and HDO at the same visit. A
      Pearson product moment correlation coefficient was determined for each
      combination of measures and tested for significance with a paired t-test. Limits
      of agreement between 2 measures were determined by the 95% confidence interval of
      the average difference of the means and illustrated by Bland-Altman plots.
      RESULTS: Systolic pressure estimated from CW was significantly but only
      moderately correlated to DU (r = 0.42, p=0.0015) and HDO (r = 0.40, p=0.0021).
      Pressure estimated from DU was significantly but only moderately correlated to
      HDO (r = 0.57, p<=0.0001). Limits of agreement were wide for all measures
      including DU and CW (-61.9to 44.6 mmHg), HDO and CW (-65.2to 26.9 mmHg), and HDO
      and DU (-63.1 to 42.06 mmHg). DISCUSSION: Systolic blood pressure estimated by CW
      cannot be used interchangeably with HDO or DU in dogs with naturally occurring
      MVD.

PMID- 27037059
TI  - Properties of a novel polysiloxane-guttapercha calcium silicate-bioglass
      containing root canal sealer.
AB  - OBJECTIVE: Root canal filling sealers based on polymethyl hydrogensiloxane or
      polymethyl hydrogensiloxane-guttapercha--introduced to improve the quality of
      conventional guttapercha-based and resin-based systems--showed advantages in
      handiness and clinical application. The aim of the study was to evaluate the
      chemical-physical properties of a novel polysiloxane-guttapercha calcium silicate
      containing root canal sealer (GuttaFlow bioseal). METHODS: GuttaFlow bioseal was
      examined and compared with GuttaFlow2, RoekoSeal and MTA Fillapex sealers.
      Setting times, open and impervious porosity and apparent porosity, water
      sorption, weight loss, calcium release, and alkalinizing activity were evaluated.
      ESEM-EDX-Raman analyses of fresh materials and after soaking in simulated body
      fluid were also performed. RESULTS: Marked differences were obtained among the
      materials. GuttaFlow bioseal showed low solubility and porosity, high water
      sorption, moderate calcium release and good alkalinizing activity. MTA Fillapex
      showed the highest calcium release, alkalinizing activity and solubility,
      RoekoSeal the lowest calcium release, no alkalinizing activity, very low
      solubility and water sorption. Only GuttaFlow bioseal showed apatite forming
      ability. SIGNIFICANCE: GuttaFlow bioseal showed alkalinizing activity together
      with negligible solubility and slight calcium release. Therefore, the notable
      nucleation of apatite and apatite precursors can be related to the co-operation
      of CaSi particles (SiOH groups) with polysiloxane (SiOSi groups). The
      incorporation of a calcium silicate component into polydimethyl
      polymethylhydrogensiloxane guttapercha sealers may represent an attractive
      strategy to obtain a bioactive biointeractive flowable guttapercha sealer for
      moist/bleeding apices with bone defects in endodontic therapy.

PMID- 27037060
TI  - PKCepsilon inhibits isolation and stemness of side population cells via the
      suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell
      carcinoma cell line 769P.
AB  - Protein kinase C epsilon (PKCepsilon), a member of the novel PKC family, is known
      to be a transforming oncogene and tumor biomarker for many human solid cancers
      including renal cell carcinoma (RCC). We isolated side population (SP) cells from
      the RCC 769P cell line, and proved that those cells possess cancer stem cell
      (CSC) characteristics. In this study, to identify the function of PKCepsilon in
      cancer stemness of 769P SP cells, we reduced the expression of PKCepsilon in
      those cells, following the results demonstrated that PKCepsilon depletion had a
      negative correlation with the existence of SP cells in 769P cell line. Down
      regulation of PKCepsilon also suppresses the CSC potential of sorted 769P SP
      cells in several ways: proliferation potential, resistance to chemotherapeutics
      and in vivo tumor formation ability. Our study also reveals that PKCepsilon is
      associated with ABCB1 and this association probably contributed to the SP cells
      isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly
      regulated by PKCepsilon. Additionally, after the depletion of PKCepsilon, the
      phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP
      cells, whereas PKCepsilon overexpression could promote the phosphorylation of
      AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCepsilon down-regulation
      suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells
      through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK
      pathways that are dependent on the phosphorylation effects. Thus, PKCepsilon may
      work as an important mediator in cancer stem cell pathogenesis of renal cell
      cancer.

PMID- 27037061
TI  - Epigenetic silencing of miR-490-3p promotes development of an aggressive
      colorectal cancer phenotype through activation of the Wnt/beta-catenin signaling
      pathway.
AB  - The Wnt/beta-catenin pathway is known to contribute to colorectal cancer (CRC)
      progression, although little is known about the contribution of beta-catenin on
      this process. We investigated the role of miR-490-3p, which was recently reported
      to suppress tumorigenesis through its effect on Wnt/beta-catenin signaling. We
      found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p
      expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo
      reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis
      and inhibits cell invasiveness by repressing the initiation of epithelial-to
      mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and
      metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1)
      protein was identified as a direct target of miR-490-3p and contributes to its
      tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on
      beta-catenin expression in nuclear fractions of CRC cells, whereas FRAT1
      expression is associated with the accumulation of beta-catenin in the nucleus of
      cells, which could be weakened by transfection with miR-490-3p. Our findings
      suggest that the miR-490-3p/FRAT1/beta-catenin axis is important in CRC
      progression and provides new insight into the molecular mechanisms underlying
      CRC. They may help to confirm the pathway driving CRC aggressiveness and serve
      for the development of a novel miRNA-targeting anticancer therapy.

PMID- 27037062
TI  - Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals.
AB  - Extensive research over the past half a century indicates that reactive oxygen
      species (ROS) play an important role in cancer. Although low levels of ROS can be
      beneficial, excessive accumulation can promote cancer. One characteristic of
      cancer cells that distinguishes them from normal cells is their ability to
      produce increased numbers of ROS and their increased dependence on an antioxidant
      defense system. ROS are produced as a byproduct intracellularly by mitochondria
      and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs,
      xenobiotics, and radiation. ROS modulate various cell signaling pathways, which
      are primarily mediated through the transcription factors NF-kappaB and STAT3,
      hypoxia-inducible factor-1alpha, kinases, growth factors, cytokines and other
      proteins, and enzymes; these pathways have been linked to cellular
      transformation, inflammation, tumor survival, proliferation, invasion,
      angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic
      changes in genes, which is helpful in diagnosing diseases. This review considers
      the role of ROS in the various stages of cancer development. Finally, we provide
      evidence that nutraceuticals derived from Mother Nature are highly effective in
      eliminating cancer cells.

PMID- 27037063
TI  - Navigating the human gastrointestinal tract for oral drug delivery: Uncharted
      waters and new frontiers.
AB  - Many concepts of oral drug delivery are based on our comprehension of human
      gastrointestinal physiology. Unfortunately, we tend to oversimplify the complex
      interplay between the various physiological factors in the human gut and, in
      particular, the dynamics of these transit conditions to which oral dosage forms
      are exposed. Recent advances in spatial and temporal resolution of medical
      instrumentation as well as improved access to these technologies have facilitated
      clinical trials to characterize the dynamic processes within the human
      gastrointestinal tract. These studies have shown that highly relevant parameters
      such as fluid volumes, dosage form movement, and pH values in the lumen of the
      upper GI tract are very dynamic. As a result of these new insights into the human
      gastrointestinal environment, some common concepts and ideas of oral drug
      delivery are no longer valid and have to be reviewed in order to ensure efficacy
      and safety of oral drug therapy.

PMID- 27037065
TI  - Essential fatty acid supplementation during lactation is required to maximize the
      subsequent reproductive performance of the modern sow.
AB  - This study was conducted to investigate the effects of supplemental essential
      fatty acids (EFA) on sow reproductive efficiency and to estimate the
      concentrations of EFA required by the lactating sow for maximum subsequent
      reproduction. Data were collected on 480 sows (PIC Camborough) balanced by
      parity, with 241 and 239 sows representing Parity 1, and 3-5 (P3+), respectively.
      Sows were assigned randomly, within parity, to a 3 * 3 factorial arrangement plus
      a control diet without added lipids. Factors included linoleic (2.1%, 2.7%, and
      3.3%) and alpha-linolenic acid (0.15%, 0.30%, and 0.45%), obtained by adding 4%
      of different mixtures of canola, corn and flaxseed oils to diets. Diets were corn
      soybean meal based with 12% wheat middlings. The benefits of supplemental EFA
      were more evident for the subsequent reproduction of mature P3+ sows. For these
      sows, supplemental alpha-linolenic acid improved the proportion of sows that
      farrowed relative to sows weaned (linear P=0.080; 82.8, 80.5, and 92.8% for sows
      fed 0.15%, 0.30%, and 0.45% alpha-linolenic acid, respectively). In addition,
      supplemental linoleic acid, fed to Parity 1 and P3+ sows, tended to increase
      subsequent litter size (linear P=0.074; 13.2, 13.8 and 14.0 total pigs born for
      2.1%, 2.7% and 3.3% linoleic acid, respectively). These results demonstrate that
      a minimum dietary intake of both alpha-linolenic and linoleic acid is required
      for the modern lactating sow to achieve a maximum reproductive outcome through
      multiple mechanisms that include rapid return to estrus, increased maintenance of
      pregnancy and improved subsequent litter size.

PMID- 27037066
TI  - Erratum: Growth and the Environment of Schizosaccharomyces pombe.

PMID- 27037064
TI  - Graphene-based materials for tissue engineering.
AB  - Graphene and its chemical derivatives have been a pivotal new class of
      nanomaterials and a model system for quantum behavior. The material's excellent
      electrical conductivity, biocompatibility, surface area and thermal properties
      are of much interest to the scientific community. Two-dimensional graphene
      materials have been widely used in various biomedical research areas such as
      bioelectronics, imaging, drug delivery, and tissue engineering. In this review,
      we will highlight the recent applications of graphene-based materials in tissue
      engineering and regenerative medicine. In particular, we will discuss the
      application of graphene-based materials in cardiac, neural, bone, cartilage,
      skeletal muscle, and skin/adipose tissue engineering. We will also discuss the
      potential risk factors of graphene-based materials in tissue engineering. In
      conclusion, we will outline the opportunities in the usage of graphene-based
      materials for clinical applications.

PMID- 27037067
TI  - Isolating Lysosomes from Rat Liver.
AB  - This protocol describes the generation of a fraction enriched in lysosomes from
      rat liver. The lysosomes are rapidly isolated using density-gradient
      centrifugation with gradient media that retain the osmolarity of the lysosomes
      such that they are functional and can be used in in vitro assays. 

PMID- 27037068
TI  - Purification of Lysosomes Using Supraparamagnetic Iron Oxide Nanoparticles
      (SPIONs).
AB  - Lysosomes can be rapidly isolated from tissue culture cells using
      supraparamagnetic iron oxide particles (SPIONs). In this protocol, colloidal iron
      dextran (FeDex) particles, a type of SPION, are taken up by cultured mouse
      macrophage cells via the endocytic pathway. The SPIONs accumulate in lysosomes,
      the end point of the endocytic pathway, permitting the lysosomes to be isolated
      magnetically. The purified lysosomes are suitable for in vitro fusion assays or
      for proteomic analysis. 

PMID- 27037069
TI  - Crystal Violet Assay for Determining Viability of Cultured Cells.
AB  - Adherent cells detach from cell culture plates during cell death. This
      characteristic can be used for the indirect quantification of cell death and to
      determine differences in proliferation upon stimulation with death-inducing
      agents. One simple method to detect maintained adherence of cells is the staining
      of attached cells with crystal violet dye, which binds to proteins and DNA. Cells
      that undergo cell death lose their adherence and are subsequently lost from the
      population of cells, reducing the amount of crystal violet staining in a culture.
      This protocol describes a quick and reliable screening method that is suitable
      for the examination of the impact of chemotherapeutics or other compounds on cell
      survival and growth inhibition. However, characterization of the cause of reduced
      crystal violet staining requires additional methods detailed elsewhere. 

PMID- 27037070
TI  - Analysis of Apoptosis and Necroptosis by Fluorescence-Activated Cell Sorting.
AB  - Fluorescence-activated cell sorting (FACS) is a laser-based, biophysical
      technology that allows simultaneous multiparametric analysis. For the analysis of
      dying cells, fluorescently labeled Annexin V (Annexin V(FITC)) and propidium
      iodide (PI) are the most commonly used reagents. Instead of PI, 4',6-diamidino-2
      phenylindole (DAPI) can also be used. DAPI is a fluorescent stain that binds
      strongly to A-T-rich regions in DNA. DAPI and PI only inefficiently pass through
      an intact cell membrane and, therefore, preferentially stain dead cells. DAPI can
      be combined with Annexin V(FITC)and the potentiometric fluorescent dye,
      tetramethylrhodamine methyl ester (TMRM), which measures mitochondrial
      permeability transition and mitochondrial membrane depolarization. TMRM is a cell
      permeable fluorescent dye that is sequestered to active mitochondria, and hence
      labels live cells. On apoptosis or necroptosis the TMRM signal is lost. The
      advantage of using Annexin V(FITC)/DAPI/TMRM is that the entire cell population
      is labeled, and it is easy to distinguish living (TMRM + /Annexin V(FITC)-/DAPI-)
      from dying or dead cells (apoptosis: TMRM-/Annexin V(FITC)+ /DAPI-; necrosis:
      TMRM-/Annexin V(FITC)+ /DAPI+). This is important because cell debris
      (fluorescent negative particles) must be avoided to establish the correct
      parameters for the FACS analysis, otherwise incorrect statistical values will be
      obtained. To obtain information on the cell concentration or absolute cell counts
      in a sample, it is recommended to add an internal microsphere counting standard
      to the flow cytrometric sample. This protocol describes the FACS analysis of cell
      death in HT1080 and L929 cells, but it can be readily adapted to other cell types
      of interest. 

PMID- 27037071
TI  - Liquid Growth of Arrayed Fluorescently Tagged Saccharomyces cerevisiae Strains
      for Live-Cell High-Throughput Microscopy Screens.
AB  - This protocol describes culturing arrays of fluorescently tagged yeast strains to
      early log-phase in a 96-well format for imaging on a high-throughput (HTP)
      microscope. The method assumes the use of the synthetic genetic array (SGA)
      technique to create the array of marked strains. When this approach is coupled
      with automated image analysis, the subcellular distribution and abundance of
      tagged proteins can be systematically and quantitatively examined in different
      genetic backgrounds and/or under different growth regimes. 

PMID- 27037072
TI  - Synthetic Genetic Array Analysis.
AB  - Genetic interaction studies have been used to characterize unknown genes, assign
      membership in pathway and complex, and build a comprehensive functional map of a
      eukaryotic cell. Synthetic genetic array (SGA) methodology automates yeast
      genetic analysis and enables systematic mapping of genetic interactions. In its
      simplest form, SGA consists of a series of replica pinning steps that enable
      construction of haploid double mutants through automated mating and meiotic
      recombination. Using this method, a strain carrying a query mutation, such as a
      deletion allele of a nonessential gene or a conditional temperature-sensitive
      allele of an essential gene, can be crossed to an input array of yeast mutants,
      such as the complete set of approximately 5000 viable deletion mutants. The
      resulting output array of double mutants can be scored for genetic interactions
      based on estimates of cellular fitness derived from colony-size measurements. The
      SGA score method can be used to analyze large-scale data sets, whereas small
      scale data sets can be analyzed using SGAtools, a simple web-based interface that
      includes all the necessary analysis steps for quantifying genetic interactions. 

PMID- 27037073
TI  - A Method for Genome Editing in Human Pluripotent Stem Cells.
AB  - Human pluripotent stem cells (PSCs) hold great potential for regenerative
      medicine and currently are being used as a research tool for basic discovery and
      disease modeling. To evaluate the role of a single genetic variant, a system of
      genome editing is needed to precisely mutate any desired DNA sequence in
      isolation and measure its effect on phenotype when compared to the isogenic
      parental PSC from which it was derived. This protocol describes the general
      targeting schemes used by researchers to edit PSCs to knock out, knock-in, or
      precisely alter a single nucleotide, covering conditions for electroporation,
      clonal isolation, and screening of edited PSCs for the targeted mutation. These
      recent advances simplify the procedure for genome editing, allowing individual
      researchers to induce nearly any desired mutation to further study its function
      or to reverse a disease-causing variant for future applications in regenerative
      medicine. 

PMID- 27037074
TI  - Transformation of Schizosaccharomyces pombe: Electroporation Procedure.
AB  - Transformation ofSchizosaccharomyces pombewith DNA requires the conditioning of
      cells to promote DNA uptake followed by cell growth under conditions that select
      and maintain the plasmid or integration event. The three main methodologies are
      electroporation, treatment with lithium cations, and transformation of
      protoplasts. This protocol describes transformation by electroporation. It
      involves pretreatingS. pombecells with dithiothreitol (DTT), which increases the
      transformation efficiency once the electric pulse is applied. 

PMID- 27037075
TI  - Transformation of Schizosaccharomyces pombe: Lithium Acetate/ Dimethyl Sulfoxide
      Procedure.
AB  - Transformation ofSchizosaccharomyces pombewith DNA requires the conditioning of
      cells to promote DNA uptake followed by cell growth under conditions that select
      and maintain the plasmid or integration event. The three main methodologies are
      electroporation, treatment with lithium cations, and transformation of
      protoplasts. The lithium acetate method described here is widely used because it
      is simple and reliable. 

PMID- 27037076
TI  - Transformation of Schizosaccharomyces pombe: Protoplast Procedure.
AB  - Transformation of Schizosaccharomyces pombe with DNA requires the conditioning of
      cells to promote DNA uptake followed by cell growth under conditions that select
      and maintain the plasmid or integration event. The three main methodologies are
      electroporation, treatment with lithium cations, and transformation of
      protoplasts. The protocol for protoplast transformation, which is described here,
      is more complicated than those for electroporation or lithium acetate and thus
      less often used. However, for some strains, it remains the only reliable
      protocol.

PMID- 27037077
TI  - Techniques to Distinguish Apoptosis from Necroptosis.
AB  - The processes by which cells die are as tightly regulated as those that govern
      cell growth and proliferation. Recent studies of the molecular pathways that
      regulate and execute cell death have uncovered a plethora of signaling cascades
      that lead to distinct modes of cell death, including "apoptosis," "necrosis,"
      "autophagic cell death," and "mitotic catastrophe." Cells can readily switch from
      one form of death to another; therefore, it is vital to have the ability to
      monitor the form of death that cells are undergoing. A number of techniques are
      available that allow the detection of cell death and when combined with either
      knockdown approaches or inhibitors of specific signaling pathways, such as
      caspase or RIP kinase pathways, they allow the rapid dissection of divergent cell
      death pathways. However, techniques that reveal the end point of cell death
      cannot reconstruct the sequence of events that have led to death; therefore, they
      need to be complemented with methods that can distinguish all forms of cell
      death. Apoptotic cells frequently undergo secondary necrosis under in vitro
      culture conditions; therefore, novel methods relying on high-throughput time
      lapse fluorescence video microscopy are necessary to provide temporal resolution
      to cell death events. Further, visualizing the assembly of multiprotein signaling
      hubs that can execute apoptosis or necroptosis helps to explore the underlying
      processes. Here we introduce a suite of techniques that reliably distinguish
      necrosis from apoptosis and secondary necrosis, and that enable investigation of
      signaling platforms capable of instructing apoptosis or necroptosis. 

PMID- 27037078
TI  - Synthetic Genetic Arrays: Automation of Yeast Genetics.
AB  - Genome-sequencing efforts have led to great strides in the annotation of protein
      coding genes and other genomic elements. The current challenge is to understand
      the functional role of each gene and how genes work together to modulate cellular
      processes. Genetic interactions define phenotypic relationships between genes and
      reveal the functional organization of a cell. Synthetic genetic array (SGA)
      methodology automates yeast genetics and enables large-scale and systematic
      mapping of genetic interaction networks in the budding yeast,Saccharomyces
      cerevisiae SGA facilitates construction of an output array of double mutants from
      an input array of single mutants through a series of replica pinning steps.
      Subsequent analysis of genetic interactions from SGA-derived mutants relies on
      accurate quantification of colony size, which serves as a proxy for fitness.
      Since its development, SGA has given rise to a variety of other experimental
      approaches for functional profiling of the yeast genome and has been applied in a
      multitude of other contexts, such as genome-wide screens for synthetic dosage
      lethality and integration with high-content screening for systematic assessment
      of morphology defects. SGA-like strategies can also be implemented similarly in a
      number of other cell types and organisms, includingSchizosaccharomyces
      pombe,Escherichia coli, Caenorhabditis elegans, and human cancer cell lines. The
      genetic networks emerging from these studies not only generate functional wiring
      diagrams but may also play a key role in our understanding of the complex
      relationship between genotype and phenotype. 

PMID- 27037079
TI  - Genome Editing in Human Pluripotent Stem Cells.
AB  - Pluripotent stem cells (PSCs), defined by their capacity for self-renewal and
      differentiation into all cell types, are an integral tool for basic biological
      research and disease modeling. However, full use of PSCs for research and
      regenerative medicine requires the ability to precisely edit their DNA to correct
      disease-causing mutations and for functional analysis of genetic variations.
      Recent advances in DNA editing of human stem cells (including PSCs) have
      benefited from the use of designer nucleases capable of making double-strand
      breaks (DSBs) at specific sequences that stimulate endogenous DNA repair. The
      clustered, regularly interspaced short palindromic repeats (CRISPR)-Cas9 system
      has become the preferred designer nuclease for genome editing in human PSCs and
      other cell types. Here we describe the principles for designing a single guide
      RNA to uniquely target a gene of interest and describe strategies for disrupting,
      inserting, or replacing a specific DNA sequence in human PSCs. The improvements
      in efficiency and ease provided by these techniques allow individuals to
      precisely engineer PSCs in a way previously limited to large institutes and core
      facilities. 

PMID- 27037080
TI  - High-Throughput Microscopy-Based Screening in Saccharomyces cerevisiae.
AB  - The budding yeastSaccharomyces cerevisiaehas served as the pioneer model organism
      for virtually all genome-scale methods, including genome sequencing, DNA
      microarrays, gene deletion collections, and a variety of proteomic platforms.
      Yeast has also provided a test-bed for the development of systematic fluorescence
      based imaging screens to enable the analysis of protein localization and
      abundance in vivo. Especially important has been the integration of high
      throughput microscopy with automated image-processing methods, which has allowed
      researchers to overcome issues associated with manual image analysis and acquire
      unbiased, quantitative data. Here we provide an introduction to automated imaging
      in budding yeast. 

PMID- 27037081
TI  - How Well Can We Detect Lineage-Specific Diversification-Rate Shifts? A Simulation
      Study of Sequential AIC Methods.
AB  - Evolutionary biologists have long been fascinated by the extreme differences in
      species numbers across branches of the Tree of Life. This has motivated the
      development of statistical methods for detecting shifts in the rate of lineage
      diversification across the branches of phylogenic trees. One of the most
      frequently used methods, MEDUSA, explores a set of diversification-rate models,
      where each model assigns branches of the phylogeny to a set of diversification
      rate categories. Each model is first fit to the data, and the Akaike information
      criterion (AIC) is then used to identify the optimal diversification model.
      Surprisingly, the statistical behavior of this popular method is uncharacterized,
      which is a concern in light of: (1) the poor performance of the AIC as a means of
      choosing among models in other phylogenetic contexts; (2) the ad hoc algorithm
      used to visit diversification models, and; (3) errors that we reveal in the
      likelihood function used to fit diversification models to the phylogenetic data.
      Here, we perform an extensive simulation study demonstrating that MEDUSA (1) has
      a high false-discovery rate (on average, spurious diversification-rate shifts are
      identified [Formula: see text] of the time), and (2) provides biased estimates of
      diversification-rate parameters. Understanding the statistical behavior of MEDUSA
      is critical both to empirical researchers-in order to clarify whether these
      methods can make reliable inferences from empirical datasets-and to theoretical
      biologists-in order to clarify the specific problems that need to be solved in
      order to develop more reliable approaches for detecting shifts in the rate of
      lineage diversification. [Akaike information criterion; extinction; lineage
      specific diversification rates; phylogenetic model selection; speciation.].

PMID- 27037082
TI  - Implementing a national health research for development platform in a low-income
      country - a review of Malawi's Health Research Capacity Strengthening Initiative.
AB  - BACKGROUND: National health research for development (R4D) platforms in lower
      income countries (LICs) are few. The Health Research Capacity Strengthening
      Initiative (HRCSI, 2008-2013) was a national systems-strengthening programme in
      Malawi involved in national priority setting, decision-making on funding, and
      health research actor mobilization. METHODS: We adopted a retrospective mixed
      methods evaluation approach, starting with information gleaned from reports
      (HRCSI and Malawian) and databases (HRCSI). A framework of a health research
      system (actors and components) guided report review and interview guide
      development. From a list of 173 individuals involved in HRCSI, 30 interviewees
      were selected within categories of stakeholders. Interviews were conducted face
      to-face or via telephone/Skype over 1 month, documented with extensive notes.
      Analysis of emerging themes was iterative among co-evaluators, with synthesis
      according to the implementation stage. RESULTS: Major HRCSI outputs included (1)
      National research priority-setting: through the production of themed background
      papers by Malawian health researchers and broad consultation, HRCSI led the
      development of a National Health Research Agenda (2012-2016), widely regarded as
      one of HRCSI's foremost achievements. (2) Institutional research capacity: there
      was an overwhelming view that HRCSI had produced a step-change in the number of
      high calibre scientists in Malawi and in fostering research interest among young
      Malawians, providing support for around 56 MSc and PhD students, and over 400
      undergraduate health-related projects. (3) Knowledge sharing: HRCSI supported
      research dissemination through national and institutional meetings by sponsoring
      attendance at conferences and through close relationships with individuals in the
      print media for disseminating information. (4) Sustainability: From 2011-2013,
      HRCSI significantly improved research systems, processes and leadership in
      Malawi, but further strengthening was needed for HRCSI to be effectively
      integrated into government structures and sustained long-term. Overall, HRCSI
      carried out many components relevant to a national health research system
      coordinating platform, and became competent at managing over half of 12 areas of
      performance for research councils. Debate about its location and challenges to
      sustainability remain open questions. CONCLUSIONS: More experimentation in the
      setting-up of national health R4D platforms to promote country 'ownership' is
      needed, accompanied by evaluation processes that facilitate learning and
      knowledge exchange of better practices among key actors in health R4D systems.

PMID- 27037083
TI  - Acute cholestatic hepatitis induced by Epstein-Barr virus infection in an adult:
      a case report.
AB  - BACKGROUND: Acute cholestatic hepatitis without features of infectious
      mononucleosis is a rare presentation of primary Epstein-Barr infection, with only
      several cases previously reported in the medical literature. Early investigation
      for Epstein-Barr virus in febrile patients with deranged liver function tests and
      no demonstrable biliary obstruction on imaging can expedite both diagnosis and
      treatment, thereby avoiding costly or invasive procedures such as liver biopsy.
      CASE PRESENTATION: A 59-year-old white woman of Anglo-Saxon descent presenting
      with a febrile illness was noted to have a cholestatic picture of deranged liver
      function tests. Over the following week a progressive obstructive jaundice
      developed, with no evidence of choledocholithiasis on ultrasound or magnetic
      resonance cholangiopancreatography. Specific immunoglobulin M antibodies against
      Epstein-Barr virus were detected in her serum and the diagnosis of Epstein-Barr
      hepatitis was confirmed by polymerase chain reaction testing. Supportive
      treatment was implemented and her liver function had normalized 3 months after
      presentation. CONCLUSIONS: Epstein-Barr virus is associated with a wide variety
      of clinical manifestations and can present as cholestatic hepatitis with or
      without features of infectious mononucleosis. While the diagnosis is often
      suggested by serological testing, Epstein-Barr virus polymerase chain reaction is
      a new non-invasive laboratory study that can help identify infection in cases
      where the clinical presentation is atypical.

PMID- 27037084
TI  - Varicella Zoster Virus Infection in Granulomatous Arteritis of the Aorta.
AB  - Granulomatous arteritis characterizes the pathology of giant cell arteritis,
      granulomatous aortitis, and intracerebral varicella zoster virus (VZV)
      vasculopathy. Because intracerebral VZV vasculopathy and giant cell arteritis are
      strongly associated with productive VZV infection in cerebral and temporal
      arteries, respectively, we evaluated human aortas for VZV antigen and VZV DNA.
      Using 3 different anti-VZV antibodies, we identified VZV antigen in 11 of 11
      aortas with pathologically verified granulomatous arteritis, in 1 of 1 cases of
      nongranulomatous arteritis, and in 5 of 18 control aortas (28%) obtained at
      autopsy. The presence of VZV antigen in granulomatous aortitis was highly
      significant (P = .0001) as compared to control aortas, in which VZV antigen was
      never associated with pathology, indicating subclinical reactivation. VZV DNA was
      found in most aortas containing VZV antigen. The frequent clinical, radiological,
      and pathological aortic involvement in patients with giant cell arteritis
      correlates with the significant detection of VZV in granulomatous aortitis.

PMID- 27037085
TI  - Varicella Zoster Virus and Giant Cell Arteritis.

PMID- 27037087
TI  - Patients are also people.

PMID- 27037086
TI  - A local insult of okadaic acid in wild-type mice induces tau phosphorylation and
      protein aggregation in anatomically distinct brain regions.
AB  - In Alzheimer's disease (AD), the distribution and density of neurofibrillary
      tangles, a histological hallmark comprised predominately of phosphorylated tau
      protein, follows a distinct pattern through anatomically connected brain regions.
      Studies in transgenic mice engineered to regionally confine tau expression have
      suggested spreading of tau within neural networks. Furthermore, injection of
      protein lysates isolated from brains of transgenic mice or patients with
      tauopathies, including AD, were shown to behave like seeds, accelerating tau
      pathology and tangle formation in predisposed mice. However, it remains unclear
      how the initiation of primary aggregation events occurs and what triggers further
      dissemination throughout the neural system. To consolidate these findings, we
      pursued an alternative approach to assess the spreading of endogenous
      phosphorylated tau. To generate endogenous seeds, 130 nl of 100 MUM protein
      phosphatase 2A inhibitor okadaic acid (OA) was injected unilaterally into the
      amygdala of 8-month-old C57Bl/6 wild-type mice. OA was detected in brain tissue
      by ELISA, and found to be restricted to the injected hemispheric quadrant, where
      it remained detectable a week post-injection. OA injection induced tau
      phosphorylation that was observed not only at the injection site but also in
      anatomically distinct areas across both hemispheres, including the cortex and
      hippocampus 24 h post-injection. An increase in insoluble tau was also observed
      in both hemispheres of injected brains by 7 days. Furthermore, thioflavin-S
      detected protein aggregation at the injection site and in the cortex of both
      injected and contralateral hemispheres. OA injection induced no thioflavin
      positivity in tau knock-out mice. The data demonstrates that a local OA insult
      can rapidly initiate changes in protein phosphorylation, solubility and
      aggregation at anatomically distant sites. This model suggests that tau
      phosphorylation can be both a primary response to an insult, and a secondary
      response communicated to non-exposed brains regions. The study highlights the use
      of OA to assist in understanding the initiation of tau spreading in vivo. 

PMID- 27037091
TI  - Relationship between pain relief, reduction in pain-associated sleep
      interference, and overall impression of improvement in patients with postherpetic
      neuralgia treated with extended-release gabapentin.
AB  - BACKGROUND: Postherpetic neuralgia (PHN) interferes with patients' quality of
      life, and disturbed sleep is a prevalent complaint. Pain-associated sleep
      interference in turn enhances pain and/or reduces pain tolerance. Therefore,
      reducing sleep interference by pain, in addition to pain control, may improve
      patient care. To address this notion, we characterized relationships among
      changes in pain intensity, sleep interference, and overall impression of
      improvement in PHN patients treated with gastroretentive gabapentin (G-GR).
      METHODS: Patients with PHN (n = 556) received G-GR 1,800 mg once-daily in two
      phase 3 and one phase 4 study. Visual Analog Scale (VAS) and Brief Pain Inventory
      (BPI) were completed at baseline and the end of study. Patients' Global
      Impression of Change (PGIC) was completed at the end of study. Regression
      analyses examined relationships between VAS, BPI sleep interference by pain, and
      PGIC. RESULTS: At the end of treatment, 53.7 and 63.2 % of patients reported a >=
      30 % reduction in VAS and BPI pain-associated sleep interference (BPISI)
      respectively; 46.3 % reported feeling "Much" or "Very Much" improved on the PGIC.
      There were positive correlations between the percent reductions in VAS and BPISI;
      both correlated with PGIC improvements. Percent changes in VAS and BPISI were
      significant (p < 0.0001 and p = 0.0082, respectively), and were independent
      predictors of feeling "Much" or "Very Much" improved on the PGIC. CONCLUSIONS:
      Reductions in pain intensity and in BPISI were correlated, and both also
      correlated with overall impression of improvement for patients with PHN treated
      with G-GR. Both pain relief and improvement BPISI independently predicted
      improvement in PGIC. For optimal patient care, clinicians should consider
      reducing the impact of pain on quality of sleep as well as overall pain
      reduction. TRIAL REGISTRATION: ClinicalTrials.gov numbers, NCT00335933 ,
      NCT00636636 , NCT01426230.

PMID- 27037092
TI  - Cystatin C-based glomerular filtration rate associates more closely with
      mortality than creatinine-based or combined glomerular filtration rate equations
      in unselected patients.
AB  - BACKGROUND: Decreased glomerular filtration rate (GFR) is an important
      cardiovascular risk factor, but estimated GFR (eGFR) may differ depending on
      whether it is based on creatinine or cystatin C. A combined creatinine/cystatin C
      equation has recently been shown to best estimate GFR; however, the benefits of
      using the combined equation for risk prediction in routine clinical care have
      been less studied. This study compares mortality risk prediction by eGFR using
      the combined creatinine/cystatin C equation (CKD-EPI), a sole creatinine equation
      (CKD-EPI) and a sole cystatin C equation (CAPA), respectively, using assays that
      are traceable to international calibrators. METHODS AND RESULTS: All patients
      analysed for both creatinine and cystatin C from the same blood sample tube (n =
      13,054) during 2005-2007 in Uppsala University Hospital Laboratory were divided
      into eGFR risk categories>60, 30-60 and <30 mL/min/1.73 m(2) by each eGFR
      equation. During follow-up (median 4.6 years), 4398 participants died, of which
      1396 deaths were due to cardiovascular causes. Reduced eGFR was significantly
      associated with death as assessed by all eGFR equations. The net reclassification
      improvement (NRI) for the combination equation compared with the sole creatinine
      equation was 0.10 (p < 0.001) for all-cause mortality and 0.08 (p < 0.001) for
      cardiovascular mortality, indicating improved reclassification. In contrast, NRI
      for the combination equation, compared with the sole cystatin C equation, was 
      0.06 (p < 0.001) for all-cause mortality and -0.02 (p = 0.032) for cardiovascular
      mortality, indicating a worsened reclassification. CONCLUSIONS: In routine
      clinical care, cystatin C-based eGFR was more closely associated with mortality
      compared with both creatinine-based eGFR and creatinine/cystatin C-based eGFR.

PMID- 27037093
TI  - Effects of interleukin-1beta on cortical spreading depolarization and cerebral
      vasculature.
AB  - During brain damage and ischemia, the cytokine interleukin-1beta is rapidly
      upregulated due to activation of inflammasomes. We studied whether interleukin
      1beta influences cortical spreading depolarization, and whether
      lipopolysaccharide, often used for microglial stimulation, influences cortical
      spreading depolarizations. In anaesthetized rats, cortical spreading
      depolarizations were elicited by microinjection of KCl. Interleukin-1beta, the IL
      1 receptor 1 antagonist, the GABAA receptor blocker bicuculline, and
      lipopolysaccharide were administered either alone or combined (interleukin-1beta
      + IL-1 receptor 1 antagonist; interleukin-1beta + bicuculline; lipopolysaccharide
      + IL-1 receptor 1 antagonist) into a local cortical treatment area. Using
      microelectrodes, cortical spreading depolarizations were recorded in a non
      treatment and in the treatment area. Plasma extravasation in cortical grey matter
      was assessed with Evans blue. Local application of interleukin-1beta reduced
      cortical spreading depolarization amplitudes in the treatment area, but not at a
      high dose. This reduction was prevented by IL-1 receptor 1 antagonist and by
      bicuculline. However, interleukin-1beta induced pronounced plasma extravasation
      independently on cortical spreading depolarizations. Application of
      lipopolysaccharide reduced cortical spreading depolarization amplitudes but
      prolonged their duration; EEG activity was still present. These effects were also
      blocked by IL-1 receptor 1 antagonist. Interleukin-1beta evokes changes of
      neuronal activity and of vascular functions. Thus, although the reduction of
      cortical spreading depolarization amplitudes at lower doses of interleukin-1beta
      may reduce deleterious effects of cortical spreading depolarizations, the sum of
      interleukin-1beta effects on excitability and on the vasculature rather promote
      brain damaging mechanisms.

PMID- 27037094
TI  - Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in
      mild cognitive impairment patients.
AB  - Reductions of cerebral blood flow and gray matter structure have been implicated
      in early pathogenesis of Alzheimer's disease, potentially providing complementary
      information. The present study evaluated regional patterns of cerebral
      hypoperfusion and atrophy in patients with mild cognitive impairment and healthy
      older adults. In each participant, cerebral perfusion and gray matter structure
      were extracted within selected brain regions vulnerable to Alzheimer's disease
      using magnetic resonance imaging. Measures were compared between diagnostic
      groups with/without adjustment for covariates. In mild cognitive impairment
      patients, cerebral blood flow was significantly reduced in comparison with
      healthy controls in temporo-parietal regions and the basal ganglia in the absence
      of local gray matter atrophy. By contrast, gray matter structure was
      significantly reduced in the hippocampus in the absence of local hypoperfusion.
      Both, cerebral perfusion and gray matter structure were significantly reduced in
      the entorhinal and isthmus cingulate cortex in mild cognitive impairment patients
      compared with healthy older adults. Our results demonstrated partly divergent
      patterns of temporo-parietal hypoperfusion and medial-temporal atrophy in mild
      cognitive impairment patients, potentially indicating biomarker sensitivity to
      dissociable pathological mechanisms. The findings support applicability of
      cerebral perfusion and gray matter structure as complementary magnetic resonance
      imaging-based biomarkers in early Alzheimer's disease detection, a hypothesis to
      be further evaluated in longitudinal studies.

PMID- 27037095
TI  - Effect of polysaccharide from Bacillus subtilis sp. on cardiovascular diseases
      and atherogenic indices in diabetic rats.
AB  - BACKGROUND: Diabetes mellitus induces chronic complications such as
      cardiovascular damage, cataracts and retinopathy, nephropathy, and
      polyneuropathy. The main aim of the study was to isolate and identify both of
      bacterial strain and exopolysaccharide to assess the possible efficiency of
      exopolysaccharide (BSEPS) from Bacillus subtilus sp .suppress on cardiovascular
      diseases, atherogenic and coronary risk indices in diabetic rats. METHODS: The
      bacterial strain used was isolated from mangrove tree sediment by serial dilution
      and the spread-plate technique and identified by morphological, physiological,
      and biochemical characteristics, and by 16S rRNA analysis. The BSEPS was
      extracted from the bacterial supernatant by four volumes child ethanol then the
      functional groups, MW and chemical analysis were detected by Fourier-transform
      infrared (FTIR), gel permeation chromatograph (GPC) and High-performance liquid
      chromatography (HPLC). Also an antioxidant activity was measured by using 2,2
      diphenyl-1-picrylhydrazyl (DPPH). Thirty-two male Sprague-Dawley rats were
      equally randomized into four groups: control group supplemented with normal
      saline (Group I); the second group supplemented with BSEPS (Group II); diabetic
      group supplemented with normal saline (Group III) and the diabetic group
      supplemented with BSEPS (Group IV). Diabetes was induced by Streptozotocin (STZ)
      (65 mg/kg BW) intraperitoneally. BSEPS (100 mg/kg BW) was administered orally for
      four weeks, following STZ induction. RESULTS: The isolated strain was identified
      based on 16S rRNA sequence as Bacillus subtilis sp. suppress. A preliminary
      chemical analysis of BSEPS indicated that the monosaccharides were mannuronic
      acid, glucuronic acid, glucose, galactose, and mannose in a molar ratio of
      1.6:1.5:1.0:2.3:1.4, respectively, with a molecular weight of 1.66 * 10(4) g mol(
      1) and a molecular number of 7.64 * 10(3) g mol(-1). BSEPS inhibited 2,2-diphenyl
      1-picrylhydrazyl radical activity, and BSEPS supplement reduced glucose (p <
      0.05) and troponin levels while insulin levels increased (p < 0.05). BSEPS also
      reduced total serum cholesterol, low-density lipoprotein (LDL), very low-density
      lipoprotein (VLDL), and triglycerides, and elevated high-density lipoprotein
      cholesterol (HDL). In parallel, intercellular adhesion molecule (ICAM), and
      vascular cell adhesion molecule (VCAM) levels in STZ-induced diabetic rats were
      reduced. Moreover, polysaccharides reduced atherogenic and coronary risk indices,
      which were confirmed by histopathological examination of the heart and aorta.
      CONCLUSIONS: Our study suggests that BSEPS improves hyperglycemia, dyslipidemia,
      and cardiovascular disease risk in STZ-induced diabetic rats.

PMID- 27037096
TI  - Effects of a transitional palliative care model on patients with end-stage heart
      failure: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Heart failure (HF) is characterized by high rates of readmission
      after hospitalization, and readmission is a major contributor to healthcare
      costs. The transitional care model has proven efficacy in reducing the
      readmission rate and economic outcomes, and increasing satisfaction with care.
      However, the effectiveness of the transitional care model has not been evaluated
      in patients with end-stage HF. This study was designed to compare the customary
      hospital-based care and a comprehensive transitional care model, namely the Home
      based Palliative HF Program (HPHP), in terms of readmission rate, quality of
      life, and satisfaction with care among end-stage HF patients under palliative
      care. METHODS/DESIGN: This is a randomized controlled trial taking place in
      hospitals in Hong Kong. We have been recruiting patients with end-stage HF who
      are identified as appropriate for palliative care during hospitalization, on
      referral by their physicians. A set of questionnaires is collected from each
      participant upon discharge. Participants are randomized to receive usual care
      (customary hospital-based care) or the intervention (HPHP). The HPHP will be
      implemented for up to 12 months. Outcome measures will be performed at 1, 3, 6,
      and 12 months post-discharge. The primary outcome of this study is quality of
      life measured by the Chronic Heart Failure Questionnaire - Chinese version;
      secondary outcomes include readmission rate, symptom intensity, functional
      status, and satisfaction with care. DISCUSSION: This study is original and will
      provide important information for service development in the area of palliative
      care. The introduction of palliative care to end-stage organ failure patients is
      new and has received increasing attention worldwide in the last decade. This
      study adopts the randomized controlled trial, a vigorous research design, to
      establish scientific evidence in exploring the best model for end-stage HF
      patients receiving palliative care. TRIAL REGISTRATION: This trial was registered
      as NCT02086305 on 7 March 2014 in the United States Clinical Trials Registration,
      and in the Clinical Trials Registry, Hong Kong University with the trial number
      UW12202.

PMID- 27037097
TI  - India needs to reduce incidental injuries to enhance productivity.

PMID- 27037098
TI  - Zika Virus--Pediatricians Be Aware.

PMID- 27037099
TI  - Hematopoietic Stem Cell Transplantation in Children and Adolescents.

PMID- 27037100
TI  - Physical Abuse of Children.

PMID- 27037101
TI  - Addendum for Meningitis.

PMID- 27037102
TI  - Syncope.

PMID- 27037103
TI  - Diplopia in a 15-year-old Boy.

PMID- 27037104
TI  - Acute Onset of Lower Extremity Weakness in a 16-year-old Korean Boy.

PMID- 27037105
TI  - Altered Mental Status in a 14-Year-Old Girl.

PMID- 27037106
TI  - Chagas Disease.

PMID- 27037107
TI  - Dengue and Chikungunya.

PMID- 27037108
TI  - Complementary, Integrative, and Holistic Medicine: Integrative Approaches to
      Pediatric Irritable Bowel Syndrome.

PMID- 27037109
TI  - Two Cases of Abdominal Pain after Trauma.

PMID- 27037110
TI  - HIV community viral load trends in South Carolina.
AB  - Community viral load is an aggregate measure of HIV viral load in a particular
      geographic location, community, or subgroup. Community viral load provides a
      measure of disease burden in a community and community transmission risk. This
      study aims to examine community viral load trend in South Carolina and identify
      differences in community viral load trends between selected population subgroups
      using a state-wide surveillance dataset that maintains electronic records of all
      HIV viral load measurements reported to the state health department. Community
      viral load trends were examined using random mixed effects models, adjusting for
      age, race, gender, residence, CD4 counts, HIV risk group, and initial
      antiretroviral regimen during the study period, and time. The community viral
      load gradually decreased from 2004 to 2013 ( p < 0.0001). The number of new
      infections also decreased ( p = 0.0001) over time. A faster rate of decrease was
      seen among men compared to women ( p < 0.0001), men who have sex with men ( p =
      0.0001) compared to heterosexuals, patients diagnosed in urban areas compared to
      that in rural areas ( p = 0.0004), and patients prescribed single-tablet regimen
      compared to multiple-tablet regimen ( p < 0.0001). While the state-wide community
      viral load decreased over time, the decline was not uniform among residence at
      diagnosis, HIV risk group, and single-tablet regimen versus multiple-tablet
      regimen subgroups. Slower declines in community viral load among females, those
      in rural areas, and heterosexuals suggest possible disparities in care that
      require further exploration. The association between using single-tablet regimen
      and faster community viral load decline is noteworthy.

PMID- 27037111
TI  - Attributes of diagnostic tests to increase uptake of dual testing for syphilis
      and HIV in Port-au-Prince, Haiti.
AB  - Introduction Syphilis and HIV screening is highly recommended for pregnant women
      and those at risk for infection. We used conjoint analysis to identify factors
      associated with testing preferences for HIV and syphilis infection. Methods We
      recruited 298 men and women 18 years and over seeking testing or care at GHESKIO
      (Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections) clinics.
      We created eight hypothetical dual HIV-syphilis test profiles varying across six
      dichotomous attributes. Participants were asked to rate each profile using Likert
      preference scales. An impact score was generated for each attribute by taking the
      difference between the preference scores for the preferred and non-preferred
      level of each attribute. Two-sided one-sample t-test was used to generate p
      values. Results Of 298 study participants, 61 (20.5%) were male. Of 237 females,
      49 (20.7%) were pregnant. Cost (free vs. US$4; p < .0001) had the highest impact
      on willingness to test, followed by number of blood draws (1 vs. 2; p < .0001),
      blood draw method (fingerprick vs. venipuncture; p < .0001), test type (rapid vs.
      laboratory; p = .0005), and time-to-result (20 minutes vs. 1 week; p = .0139).
      Conclusion HIV and syphilis testing preferences for this study sample in Port-au
      Prince prioritized cost, single fingerprick, laboratory-based testing and
      timeliness.

PMID- 27037112
TI  - Molecular detection of Feline Leukemia Virus in free-ranging jaguars (Panthera
      onca) in the Pantanal region of Mato Grosso, Brazil.

PMID- 27037113
TI  - Abnormal anal cytology risk in women with known genital squamous intraepithelial
      lesion.
AB  - The purpose of this study was to assess the risk of abnormal anal cytology in
      women with known genital squamous intraepithelial lesion. This study evaluated
      200 women with and without genital squamous intraepithelial lesion who were
      recruited for anal Pap smears. Women who had abnormal results on equally or over
      atypical squamous cells of undetermined significance were classified as having
      abnormal anal cytology. A multiple logistic regression analysis (stepwise) was
      performed to identify the risk for developing abnormal anal cytology. Data were
      analyzed using the SPSS 20.0 program. The average age was 41.09 (+/-12.64). Of
      the total participants, 75.5% did not practice anal sex, 91% did not have HPV
      infected partners, 92% did not have any anal pathology, and 68.5% did not have
      anal bleeding. More than half (57.5%) had genital SIL and a significant number
      developed abnormal anal cytology: 13% in the total sample and 17.4% in women with
      genital SIL. A significant association was observed between genital squamous
      intraepithelial lesion and anal squamous intraepithelial lesion (PR=2.46;
      p=0.03). In the logistic regression model, women having genital intraepithelial
      lesion were more likely to have abnormal anal Pap smear (aPR=2.81; p=0.02). This
      report shows that women with genital squamous intraepithelial lesion must be more
      closely screened for anal cancer. 

PMID- 27037114
TI  - Constitutive Expression of a Nag-Like Dioxygenase Gene through an Internal
      Promoter in the 2-Chloronitrobenzene Catabolism Gene Cluster of Pseudomonas
      stutzeri ZWLR2-1.
AB  - The gene cluster encoding the 2-chloronitrobenzene (2CNB) catabolism pathway in
      Pseudomonas stutzeri ZWLR2-1 is a patchwork assembly of a Nag-like dioxygenase
      (dioxygenase belonging to the naphthalene dioxygenase NagAaAbAcAd family from
      Ralstonia sp. strain U2) gene cluster and a chlorocatechol catabolism cluster.
      However, the transcriptional regulator gene usually present in the Nag-like
      dioxygenase gene cluster is missing, leaving it unclear how this cluster is
      expressed. The pattern of expression of the 2CNB catabolism cluster was
      investigated here. The results demonstrate that the expression was constitutive
      and not induced by its substrate 2CNB or salicylate, the usual inducer of
      expression in the Nag-like dioxygenase family. Reverse transcription-PCR
      indicated the presence of at least one transcript containing all the structural
      genes for 2CNB degradation. Among the three promoters verified in the gene
      cluster, P1 served as the promoter for the entire catabolism operon, but the
      internal promoters P2 and P3 also enhanced the transcription of the genes
      downstream. The P3 promoter, which was not previously defined as a promoter
      sequence, was the strongest of these three promoters. It drove the expression of
      cnbAcAd encoding the dioxygenase that catalyzes the initial reaction in the 2CNB
      catabolism pathway. Bioinformatics and mutation analyses suggested that this P3
      promoter evolved through the duplication of an 18-bp fragment and introduction of
      an extra 132-bp fragment. IMPORTANCE: The release of many synthetic compounds
      into the environment places selective pressure on bacteria to develop their
      ability to utilize these chemicals to grow. One of the problems that a bacterium
      must surmount is to evolve a regulatory device for expression of the
      corresponding catabolism genes. Considering that 2CNB is a xenobiotic that has
      existed only since the onset of synthetic chemistry, it may be a good example for
      studying the molecular mechanisms underlying rapid evolution in regulatory
      networks for the catabolism of synthetic compounds. The 2CNB utilizer Pseudomonas
      stutzeri ZWLR2-1 in this study has adapted itself to the new pollutant by
      evolving the always-inducible Nag-like dioxygenase into a constitutively
      expressed enzyme, and its expression has escaped the influence of salicylate.
      This may facilitate an understanding of how bacteria can rapidly adapt to the new
      synthetic compounds by evolving its expression system for key enzymes involved in
      the degradation of a xenobiotic.

PMID- 27037115
TI  - An Efficient Method To Generate Gene Deletion Mutants of the Rapamycin-Producing
      Bacterium Streptomyces iranensis HM 35.
AB  - Streptomyces iranensis HM 35 is an alternative rapamycin producer to Streptomyces
      rapamycinicus Targeted genetic modification of rapamycin-producing actinomycetes
      is a powerful tool for the directed production of rapamycin derivatives, and it
      has also revealed some key features of the molecular biology of rapamycin
      formation in S. rapamycinicus. The approach depends upon efficient conjugational
      plasmid transfer from Escherichia coli to Streptomyces, and the failure of this
      step has frustrated its application to Streptomyces iranensis HM 35. Here, by
      systematically optimizing the process of conjugational plasmid transfer,
      including screening of various media, and by defining optimal temperatures and
      concentrations of antibiotics and Ca(2+) ions in the conjugation media, we have
      achieved exconjugant formation for each of a series of gene deletions in S.
      iranensis HM 35. Among them were rapK, which generates the starter unit for
      rapamycin biosynthesis, and hutF, encoding a histidine catabolizing enzyme. The
      protocol that we have developed may allow efficient generation of targeted gene
      knockout mutants of Streptomyces species that are genetically difficult to
      manipulate. IMPORTANCE: The developed protocol of conjugational plasmid transfer
      from Escherichia coli to Streptomyces iranensis may allow efficient generation of
      targeted gene knockout mutants of other genetically difficult to manipulate, but
      valuable, Streptomyces species.

PMID- 27037116
TI  - Colony Location and Captivity Influence the Gut Microbial Community Composition
      of the Australian Sea Lion (Neophoca cinerea).
AB  - Gut microbiota play an important role in maintenance of mammalian metabolism and
      immune system regulation, and disturbances to this community can have adverse
      impacts on animal health. To better understand the composition of gut microbiota
      in marine mammals, fecal bacterial communities of the Australian sea lion
      (Neophoca cinerea), an endangered pinniped with localized distribution, were
      examined. A comparison of samples from individuals across 11 wild colonies in
      South and Western Australia and three Australian captive populations showed five
      dominant bacterial phyla: Firmicutes, Proteobacteria, Bacteroidetes,
      Actinobacteria, and Fusobacteria The phylum Firmicutes was dominant in both wild
      (76.4% +/- 4.73%) and captive animals (61.4% +/- 10.8%), while Proteobacteria
      contributed more to captive (29.3% +/- 11.5%) than to wild (10.6% +/- 3.43%)
      fecal communities. Qualitative differences were observed between fecal
      communities from wild and captive animals based on principal-coordinate analysis.
      SIMPER (similarity percentage procedure) analyses indicated that operational
      taxonomic units (OTU) from the bacterial families Clostridiaceae and
      Ruminococcaceae were more abundant in wild than in captive animals and
      contributed most to the average dissimilarity between groups (SIMPER
      contributions of 19.1% and 10.9%, respectively). Differences in the biological
      environment, the foraging site fidelity, and anthropogenic impacts may provide
      various opportunities for unique microbial establishment in Australian sea lions.
      As anthropogenic disturbances to marine mammals are likely to increase,
      understanding the potential for such disturbances to impact microbial community
      compositions and subsequently affect animal health will be beneficial for
      management of these vulnerable species. IMPORTANCE: The Australian sea lion is an
      endangered species for which there is currently little information regarding
      disease and microbial ecology. In this work, we present an in-depth study of the
      fecal microbiota of a large number of Australian sea lions from geographically
      diverse wild and captive populations. Colony location and captivity were found to
      influence the gut microbial community compositions of these animals. Our findings
      significantly extend the baseline knowledge of marine mammal gut microbiome
      composition and variability.

PMID- 27037117
TI  - Regulatory Activities of Four ArsR Proteins in Agrobacterium tumefaciens 5A.
AB  - ArsR is a well-studied transcriptional repressor that regulates microbe-arsenic
      interactions. Most microorganisms have an arsR gene, but in cases where multiple
      copies exist, the respective roles or potential functional overlap have not been
      explored. We examined the repressors encoded by arsR1 and arsR2 (ars1 operon) and
      by arsR3 and arsR4 (ars2 operon) in Agrobacterium tumefaciens 5A. ArsR1 and ArsR4
      are very similar in their primary sequences and diverge phylogenetically from
      ArsR2 and ArsR3, which are also quite similar to one another. Reporter constructs
      (lacZ) for arsR1, arsR2, and arsR4 were all inducible by As(III), but expression
      of arsR3 (monitored by reverse transcriptase PCR) was not influenced by As(III)
      and appeared to be linked transcriptionally to an upstream lysR-type gene.
      Experiments using a combination of deletion mutations and additional reporter
      assays illustrated that the encoded repressors (i) are not all autoregulatory as
      is typically known for ArsR proteins, (ii) exhibit variable control of each
      other's encoding genes, and (iii) exert variable control of other genes
      previously shown to be under the control of ArsR1. Furthermore, ArsR2, ArsR3, and
      ArsR4 appear to have an activator-like function for some genes otherwise
      repressed by ArsR1, which deviates from the well-studied repressor role of ArsR
      proteins. The differential regulatory activities suggest a complex regulatory
      network not previously observed in ArsR studies. The results indicate that fine
      scale ArsR sequence deviations of the reiterated regulatory proteins apparently
      translate to different regulatory roles. IMPORTANCE: Given the significance of
      the ArsR repressor in regulating various aspects of microbe-arsenic interactions,
      it is important to assess potential regulatory overlap and/or interference when a
      microorganism carries multiple copies of arsR This study explores this issue and
      shows that the four arsR genes in A. tumefaciens 5A, associated with two separate
      ars operons, encode proteins exhibiting various degrees of functional overlap
      with respect to autoregulation and cross-regulation, as well as control of other
      functional genes. In some cases, differences in regulatory activity are
      associated with only limited differences in protein primary structure. The
      experiments summarized herein also present evidence that ArsR proteins appear to
      have activator functions, representing novel regulatory activities for ArsR,
      previously known only to be a repressor.

PMID- 27037118
TI  - Short-Term Exposure to Coal Combustion Waste Has Little Impact on the Skin
      Microbiome of Adult Spring Peepers (Pseudacris crucifer).
AB  - Disruptions to the microbiome can impact host health as can exposure to
      environmental contaminants. However, few studies have addressed how environmental
      contaminants impact the microbiome. We explored this question for frogs that
      breed in wetlands contaminated with fly ash, a by-product of coal combustion that
      is enriched in trace elements. We found differences in the bacterial communities
      among a fly ash-contaminated site and several reference wetlands. We then
      experimentally assessed the impacts of fly ash on the skin microbiome of adult
      spring peepers (Pseudacris crucifer). Frogs were exposed to fly ash in the
      laboratory for 12 h, the duration of a typical breeding event, and the skin
      microbiome was assessed after 5 days (experiment 1) or after 5 and 15 days
      (experiment 2). We examined bacterial community structure using 16S rRNA gene
      amplicon sequencing and metabolite profiles using high-pressure liquid
      chromatography-mass spectrometry (HPLC-MS). We found little impact as the result
      of acute exposure to fly ash on the bacterial communities or metabolite profiles
      in either experiment, suggesting that the bacterial symbiont communities of
      adults may be relatively resistant to brief contaminant exposure. However,
      housing frogs in the laboratory altered bacterial community structure in the two
      experiments, which supports prior research suggesting that environmental source
      pools are important for maintaining the amphibian skin microbiome. Therefore, for
      contaminants like fly ash that may alter the potential source pool of symbionts,
      we think it may be important to explore how contaminants affect the initial
      assembly of the amphibian skin microbiome in larval amphibians that develop
      within contaminated sites. IMPORTANCE: Animals are hosts to many symbiotic
      microorganisms, collectively called the microbiome, that play critical roles in
      host health. Therefore, environmental contaminants that alter the microbiome may
      impact hosts. Some of the most widespread contaminants, produced worldwide, are
      derived from the mining, storage, and combustion of coal for energy. Fly ash, for
      example, is a by-product of coal combustion. It contains compounds such as
      arsenic, selenium, cadmium, and strontium and is a recognized source of ground
      and surface water contamination. Here, we experimentally investigated the impacts
      of short-term fly ash exposure on the skin microbiome of spring peepers, one of
      many species of amphibian that sometimes breed in open fly ash disposal ponds.
      This research provides a look into the potential impacts of fly ash on an
      animal's microbiome and suggests important future directions for research on the
      effects of environmental contaminants on the microbiome.

PMID- 27037119
TI  - Origin of Chemical Diversity in Prochloron-Tunicate Symbiosis.
AB  - Diversity-generating metabolism leads to the evolution of many different
      chemicals in living organisms. Here, by examining a marine symbiosis, we provide
      a precise evolutionary model of how nature generates a family of novel chemicals,
      the cyanobactins. We show that tunicates and their symbiotic Prochloron
      cyanobacteria share congruent phylogenies, indicating that Prochloron phylogeny
      is related to host phylogeny and not to external habitat or geography. We observe
      that Prochloron exchanges discrete functional genetic modules for cyanobactin
      secondary metabolite biosynthesis in an otherwise conserved genetic background.
      The module exchange leads to gain or loss of discrete chemical functional groups.
      Because the underlying enzymes exhibit broad substrate tolerance, discrete
      exchange of substrates and enzymes between Prochloron strains leads to the rapid
      generation of chemical novelty. These results have implications in choosing
      biochemical pathways and enzymes for engineered or combinatorial biosynthesis.
      IMPORTANCE: While most biosynthetic pathways lead to one or a few products, a
      subset of pathways are diversity generating and are capable of producing
      thousands to millions of derivatives. This property is highly useful in
      biotechnology since it enables biochemical or synthetic biological methods to
      create desired chemicals. A fundamental question has been how nature itself
      creates this chemical diversity. Here, by examining the symbiosis between coral
      reef animals and bacteria, we describe the genetic basis of chemical variation
      with unprecedented precision. New compounds from the cyanobactin family are
      created by either varying the substrate or importing needed enzymatic functions
      from other organisms or via both mechanisms. This natural process matches
      successful laboratory strategies to engineer the biosynthesis of new chemicals
      and teaches a new strategy to direct biosynthesis.

PMID- 27037120
TI  - Mycoplasma agalactiae Secretion of beta-(1->6)-Glucan, a Rare Polysaccharide in
      Prokaryotes, Is Governed by High-Frequency Phase Variation.
AB  - Mycoplasmas are minimal, wall-less bacteria but have retained the ability to
      secrete complex carbohydrate polymers that constitute a glycocalyx. In members of
      the Mycoplasma mycoides cluster, which are important ruminant pathogens, the
      glycocalyx includes both cell-attached and cell-free polysaccharides. This report
      explores the potential secretion of polysaccharides by M. agalactiae, another
      ruminant pathogen that belongs to a distant phylogenetic group. Comparative
      genomic analyses showed that M. agalactiae possesses all the genes required for
      polysaccharide secretion. Notably, a putative synthase gene (gsmA) was
      identified, by in silico reconstruction of the biosynthetic pathway, that could
      be involved in both polymerization and export of the carbohydrate polymers. M.
      agalactiae polysaccharides were then purified in vitro and found to be mainly
      cell attached, with a linear beta-(1->6)-glucopyranose structure [beta-(1->6)
      glucan]. Secretion of beta-(1->6)-glucan was further shown to rely on the
      presence of a functional gsmA gene, whose expression is subjected to high
      frequency phase variation. This event is governed by the spontaneous intraclonal
      variation in length of a poly(G) tract located in the gsmA coding sequence and
      was shown to occur in most of the M. agalactiae clinical isolates tested in this
      study. M. agalactiae susceptibility to serum-killing activity appeared to be
      dictated by ON/OFF switching of beta-(1->6)-glucan secretion, suggesting a role
      of this phenomenon in survival of the pathogen when it invades the host
      bloodstream. Finally, beta-(1->6)-glucan secretion was not restricted to M.
      agalactiae but was detected also in M. mycoides subsp. capri PG3(T), another
      pathogen of small ruminants. IMPORTANCE: Many if not all bacteria are able to
      secrete polysaccharides, either attached to the cell surface or exported unbound
      into the extracellular environment. Both types of polysaccharides can play a role
      in bacterium-host interactions. Mycoplasmas are no exception despite their poor
      overall metabolic capacity. We showed here that M. agalactiae secretes a capsular
      beta-(1->6)-glucopyranose thanks to a specific glycosyltransferase with synthase
      activity. This secretion is governed by high-frequency ON/OFF phase variation
      that might be crucial in mycoplasma host dissemination, as cell-attached beta-(1
      >6)-glucopyranose increases serum-killing susceptibility. Our results provide
      functional genetic data about mycoplasmal glycosyltransferases with dual
      functions, i.e., assembly and export of the sugar polymers across the cell
      membrane. Furthermore, we demonstrated that nonprotein epitopes can be subjected
      to surface antigenic variation in mycoplasmas. Finally, the present report
      contributes to unravel the role of secreted polysaccharides in the virulence and
      pathogenicity of these peculiar bacteria.

PMID- 27037121
TI  - Metabolic Engineering of the Actinomycete Amycolatopsis sp. Strain ATCC 39116
      towards Enhanced Production of Natural Vanillin.
AB  - The Gram-positive bacterium Amycolatopsis sp. ATCC 39116 is used for the
      fermentative production of natural vanillin from ferulic acid on an industrial
      scale. The strain is known for its outstanding tolerance to this toxic product.
      In order to improve the productivity of the fermentation process, the strain's
      metabolism was engineered for higher final concentrations and molar yields.
      Degradation of vanillin could be decreased by more than 90% through deletion of
      the vdh gene, which codes for the central vanillin catabolism enzyme, vanillin
      dehydrogenase. This mutation resulted in improvement of the final concentration
      of vanillin by more than 2.2 g/liter, with a molar yield of 80.9%. Further
      improvement was achieved with constitutive expression of the vanillin anabolism
      genes ech and fcs, coding for the enzymes feruloyl-coenzyme A (CoA) synthetase
      (fcs) and enoyl-CoA hydratase/aldolase (ech). The transcription of both genes was
      shown to be induced by ferulic acid, which explains the unwanted adaptation phase
      in the fermentation process before vanillin was efficiently produced by the wild
      type cells. Through the constitutive and enhanced expression of the two genes,
      the adaptation phase was eliminated and a final vanillin concentration of 19.3
      g/liter, with a molar yield of 94.9%, was obtained. Moreover, an even higher
      final vanillin concentration of 22.3 g/liter was achieved, at the expense of a
      lower molar yield, by using an improved feeding strategy. This is the highest
      reported vanillin concentration reached in microbial fermentation processes
      without extraction of the product. Furthermore, the vanillin was produced almost
      without by-products, with a molar yield that nearly approached the theoretical
      maximum. IMPORTANCE: Much effort has been put into optimization of the
      biotechnological production of natural vanillin. The demand for this compound is
      growing due to increased consumer concerns regarding chemically produced food
      additives. Since this compound is toxic to most organisms, it has proven quite
      difficult to reach high concentrations and molar yields. This study shows that
      improvements in the final vanillin concentrations and molar yields can be made
      through a combination of modification of the fermentation parameters and
      molecular strain engineering, without the need for methods such as continuous
      extraction from the fermentation broth. Using this approach, we were able to
      reach a final vanillin concentration of 22.3 g/liter, which is the highest
      vanillin concentration reported to date that was generated with Amycolatopsis sp.
      ATCC 39116 without additional extraction of the toxic product.

PMID- 27037122
TI  - FDA Escherichia coli Identification (FDA-ECID) Microarray: a Pangenome Molecular
      Toolbox for Serotyping, Virulence Profiling, Molecular Epidemiology, and
      Phylogeny.
AB  - Most Escherichia coli strains are nonpathogenic. However, for clinical diagnosis
      and food safety analysis, current identification methods for pathogenic E. coli
      either are time-consuming and/or provide limited information. Here, we utilized a
      custom DNA microarray with informative genetic features extracted from 368
      sequence sets for rapid and high-throughput pathogen identification. The FDA
      Escherichia coli Identification (FDA-ECID) platform contains three sets of
      molecularly informative features that together stratify strain identification and
      relatedness. First, 53 known flagellin alleles, 103 alleles of wzx and wzy, and 5
      alleles of wzm provide molecular serotyping utility. Second, 41,932 probe sets
      representing the pan-genome of E. coli provide strain-level gene content
      information. Third, approximately 125,000 single nucleotide polymorphisms (SNPs)
      of available whole-genome sequences (WGS) were distilled to 9,984 SNPs capable of
      recapitulating the E. coli phylogeny. We analyzed 103 diverse E. coli strains
      with available WGS data, including those associated with past foodborne
      illnesses, to determine robustness and accuracy. The array was able to accurately
      identify the molecular O and H serotypes, potentially correcting serological
      failures and providing better resolution for H-nontypeable/nonmotile phenotypes.
      In addition, molecular risk assessment was possible with key virulence marker
      identifications. Epidemiologically, each strain had a unique comparative genomic
      fingerprint that was extended to an additional 507 food and clinical isolates.
      Finally, a 99.7% phylogenetic concordance was established between microarray
      analysis and WGS using SNP-level data for advanced genome typing. Our study
      demonstrates FDA-ECID as a powerful tool for epidemiology and molecular risk
      assessment with the capacity to profile the global landscape and diversity of E.
      coli IMPORTANCE: This study describes a robust, state-of-the-art platform
      developed from available whole-genome sequences of E. coli and Shigella spp. by
      distilling useful signatures for epidemiology and molecular risk assessment into
      one assay. The FDA-ECID microarray contains features that enable comprehensive
      molecular serotyping and virulence profiling along with genome-scale genotyping
      and SNP analysis. Hence, it is a molecular toolbox that stratifies strain
      identification and pathogenic potential in the contexts of epidemiology and
      phylogeny. We applied this tool to strains from food, environmental, and clinical
      sources, resulting in significantly greater phylogenetic and strain-specific
      resolution than previously reported for available typing methods.

PMID- 27037123
TI  - Effects of Polycyclic Aromatic Hydrocarbon Mixtures on Degradation, Gene
      Expression, and Metabolite Production in Four Mycobacterium Species.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants
      that are hazardous to human health. It has been demonstrated that members of the
      Mycobacterium genus are among the most effective degraders of PAHs, but few
      studies have focused on the degradation of PAH mixtures. In this study, single
      and mixed PAH metabolism was investigated in four phylogenetically distinct
      Mycobacterium species with respect to (i) parent compound degradation, (ii)
      bacterial growth, (iii) catabolic gene expression, and (iv) metabolite
      production. Synergistic and antagonistic effects on four model PAH compounds
      (benzo[a]pyrene, pyrene, fluoranthene, and phenanthrene) characterized
      degradation of mixtures in a strain- and mixture-dependent manner. The mixture of
      pyrene and phenanthrene, in particular, resulted in antagonized degradation by
      three out of four bacterial species, and further studies were narrowed to
      investigate the degradation of this mixture. Antagonistic effects persisted over
      time and were correlated with reduced bacterial growth. Antagonized degradation
      of PAH was not caused by preferential degradation of secondary PAHs, nor were
      mixture compounds or concentrations toxic to cells growing on sugars. Reverse
      transcription-PCR (RT-PCR) studies of the characterized catabolic pathway of
      phenanthrene showed that in one organism, antagonism of mixture degradation was
      associated with downregulated gene expression. Metabolite profiling revealed that
      antagonism in mixture degradation was associated with the shunting of substrate
      through alternative pathways not used during the degradation of single PAHs. The
      results of this study demonstrate metabolic differences between single and mixed
      PAH degradation with consequences for risk assessment and bioremediation of PAH
      contaminated sites. IMPORTANCE: Mycobacterium species are promising organisms for
      environmental bioremediation because of their ubiquitous presence in soils and
      their ability to catabolize aromatic compounds. PAHs can be degraded effectively
      as single compounds, but mixed substrates often are subject to degradative
      inhibition, which may explain the persistence of these pollutants in soils.
      Single and mixed PAH degradation by diverse Mycobacterium species was compared,
      with associated bacterial growth, gene expression, and metabolite production. The
      results demonstrate that antagonism characterized degradation in a strain- and
      mixture-dependent manner. One strain that was versatile in its pathway use of
      single chemicals also efficiently degraded the mixture, whereas antagonism in
      other the strains was associated with altered metabolic profiles, indicating
      unusual pathway use. The impacts of this work on risk assessment and
      bioremediation modeling studies indicate the need to account for mixture
      generated intermediates and to recognize mixture degradation as a property
      distinct from that of PAH substrate range.

PMID- 27037124
TI  - Calcineurin and Calcium Channel CchA Coordinate the Salt Stress Response by
      Regulating Cytoplasmic Ca2+ Homeostasis in Aspergillus nidulans.
AB  - The eukaryotic calcium/calmodulin-dependent protein phosphatase calcineurin is
      crucial for the environmental adaption of fungi. However, the mechanism of
      coordinate regulation of the response to salt stress by calcineurin and the high
      affinity calcium channel CchA in fungi is not well understood. Here we show that
      the deletion of cchA suppresses the hyphal growth defects caused by the loss of
      calcineurin under salt stress in Aspergillus nidulans Additionally, the
      hypersensitivity of the DeltacnaA strain to extracellular calcium and cell-wall
      damaging agents can be suppressed by cchA deletion. Using the calcium-sensitive
      photoprotein aequorin to monitor the cytoplasmic Ca(2+) concentration ([Ca(2+)]c)
      in living cells, we found that calcineurin negatively regulates CchA on calcium
      uptake in response to external calcium in normally cultured cells. However, in
      salt-stress-pretreated cells, loss of either cnaA or cchA significantly decreased
      the [Ca(2+)]c, but a deficiency in both cnaA and cchA switches the [Ca(2+)]c to
      the reference strain level, indicating that calcineurin and CchA synergistically
      coordinate calcium influx under salt stress. Moreover, real-time PCR results
      showed that the dysfunction of cchA in the DeltacnaA strain dramatically restored
      the expression of enaA (a major determinant for sodium detoxification), which was
      abolished in the DeltacnaA strain under salt stress. These results suggest that
      double deficiencies of cnaA and cchA could bypass the requirement of calcineurin
      to induce enaA expression under salt stress. Finally, YvcA, a member of the
      transient receptor potential channel (TRPC) protein family of vacuolar Ca(2+)
      channels, was proven to compensate for calcineurin-CchA in fungal salt stress
      adaption.IMPORTANCE The feedback inhibition relationship between calcineurin and
      the calcium channel Cch1/Mid1 has been well recognized from yeast. Interestingly,
      our previous study (S. Wang et al., PLoS One 7:e46564, 2012,
      http://dx.doi.org/10.1371/journal.pone.0046564) showed that the deletion of cchA
      could suppress the hyphal growth defects caused by the loss of calcineurin under
      salt stress in Aspergillus nidulans In this study, our findings suggest that
      fungi are able to develop a unique mechanism for adapting to environmental salt
      stress. Compared to cells cultured normally, the NaCl-pretreated cells had a
      remarkable increase in transient [Ca(2+)]c Furthermore, we show that calcineurin
      and CchA are required to modulate cellular calcium levels and synergistically
      coordinate calcium influx under salt stress. Finally, YvcA, a member of of the
      TRPC family of vacuolar Ca(2+) channels, was proven to compensate for calcineurin
      CchA in fungal salt stress adaption. The findings in this study provide insights
      into the complex regulatory links between calcineurin and CchA to maintain
      cytoplasmic Ca(2+) homeostasis in response to different environments.

PMID- 27037125
TI  - Insensitivity of Diverse and Temporally Variable Particle-Associated Microbial
      Communities to Bulk Seawater Environmental Parameters.
AB  - There is a growing recognition of the roles of marine microenvironments as
      reservoirs of biodiversity and as sites of enhanced biological activity and in
      facilitating biological interactions. Here, we examine the bacterial community
      inhabiting free-living and particle-associated seawater microenvironments at the
      Pivers Island Coastal Observatory (PICO). 16S rRNA gene libraries from monthly
      samples (July 2013 to August 2014) were used to identify microbes in seawater in
      four size fractions: >63 MUm (zooplankton and large particles), 63 to 5 MUm
      (particles), 5 to 1 MUm (small particles/dividing cells), and <1 MUm (free-living
      prokaryotes). Analyses of microbial community composition highlight the
      importance of the microhabitat (e.g., particle-associated versus free-living
      lifestyle) as communities cluster by size fraction, and the microhabitat explains
      more of the community variability than measured environmental parameters,
      including pH, particle concentration, projected daily insolation, nutrients, and
      temperature. While temperature is statistically associated with community changes
      in the <1-MUm and 5- to 1-MUm fractions, none of the measured bulk seawater
      environmental variables are statistically significant in the larger-particle
      associated fractions. These results, combined with high particle-associated
      community variability, especially in the largest size fraction (i.e., >63 MUm),
      suggest that particle composition, including eukaryotes and their associated
      microbiomes, may be an important factor in selecting for specific particle
      associated bacteria. IMPORTANCE: By comparing levels of particle-associated and
      free-living bacterial diversity at a coastal location over the course of 14
      months, we show that bacteria associated with particles are generally more
      diverse and appear to be less responsive to commonly measured environmental
      variables than free-living bacteria. These diverse and highly variable particle
      associated communities are likely driven by differences in particle substrates
      both within the water column at a single time point and due to seasonal changes
      over the course of the year.

PMID- 27037127
TI  - Immunoaffinity extraction using conformation-dependent antibodies coupled to SE
      HPLC for the development of stability and potency-indicating assay for
      quadrivalent human papillomavirus vaccine.
AB  - Quadrivalent human papillomavirus (HPV) vaccine is formulated of four types of
      non-infectious recombinant virus like particles (VLPs) that are structurally and
      immunologically similar to the corresponding infectious HPV virus types 6, 11, 16
      and 18. With almost identical physical, chemical and structural properties of the
      four types of VLPs, ELISA remains the only approved in vitro potency testing
      assay. In this study, an alternative industry-friendly, stability- and potency
      indicating assay protocol was developed and validated for the determination of
      HPV vaccine. Vacuum-driven immunoaffinity extraction (IAE) was employed using
      type-specific, conformation-dependent antibodies against each type of HPV VLPs.
      ELISA assay was employed to evaluate the ability of IAE columns to specifically
      separate each of the four types of VLPs from their quadrivalent mixture. Mean
      percentage recoveries of 76.76+/-2.69, 69.12+/-5.79, 84.86+/-5.25 and 71.14+/
      4.50% were obtained for VLPs types 6, 11, 16 and 18, respectively with no
      significant interference in each case. Antigen content was then determined using
      SE-HPLC over a concentration range of 5.00-20.00MUg/mL (r>0.998) for VLPs type 6,
      11, 16 and 18, respectively. The SE-HPLC assay was found accurate and precise
      (RSD<10.00%) with LOD ranging from 1.23-3.85MUg/mL. The assay protocol was found
      superior to conventional ELISA assay with respect to simplicity, total analysis
      time and cost. Good correlation between the results of analysis obtained using
      IAE-SE-HPLC and ELISA demonstrated the suitability of the suggested assay
      protocol for stability and potency assessment with a good potential for
      implementation for batch release. This approach should be applicable for quality
      assessment of other vaccine preparations based on VLPs. 

PMID- 27037126
TI  - Biochemical and Structural Characterizations of Two Dictyostelium
      Cellobiohydrolases from the Amoebozoa Kingdom Reveal a High Level of Conservation
      between Distant Phylogenetic Trees of Life.
AB  - Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) are enzymes commonly
      employed in plant cell wall degradation across eukaryotic kingdoms of life, as
      they provide significant hydrolytic potential in cellulose turnover. To date,
      many fungal GH7 CBHs have been examined, yet many questions regarding structure
      activity relationships in these important natural and commercial enzymes remain.
      Here, we present the crystal structures and a biochemical analysis of two GH7
      CBHs from social amoeba: Dictyostelium discoideum Cel7A (DdiCel7A) and
      Dictyostelium purpureum Cel7A (DpuCel7A). DdiCel7A and DpuCel7A natively consist
      of a catalytic domain and do not exhibit a carbohydrate-binding module (CBM). The
      structures of DdiCel7A and DpuCel7A, resolved to 2.1 A and 2.7 A, respectively,
      are homologous to those of other GH7 CBHs with an enclosed active-site tunnel.
      Two primary differences between the Dictyostelium CBHs and the archetypal model
      GH7 CBH, Trichoderma reesei Cel7A (TreCel7A), occur near the hydrolytic active
      site and the product-binding sites. To compare the activities of these enzymes
      with the activity of TreCel7A, the family 1 TreCel7A CBM and linker were added to
      the C terminus of each of the Dictyostelium enzymes, creating DdiCel7ACBM and
      DpuCel7ACBM, which were recombinantly expressed in T. reesei DdiCel7ACBM and
      DpuCel7ACBM hydrolyzed Avicel, pretreated corn stover, and phosphoric acid
      swollen cellulose as efficiently as TreCel7A when hydrolysis was compared at
      their temperature optima. The Ki of cellobiose was significantly higher for
      DdiCel7ACBM and DpuCel7ACBM than for TreCel7A: 205, 130, and 29 MUM,
      respectively. Taken together, the present study highlights the remarkable degree
      of conservation of the activity of these key natural and industrial enzymes
      across quite distant phylogenetic trees of life. IMPORTANCE: GH7 CBHs are among
      the most important cellulolytic enzymes both in nature and for emerging
      industrial applications for cellulose breakdown. Understanding the diversity of
      these key industrial enzymes is critical to engineering them for higher levels of
      activity and greater stability. The present work demonstrates that two GH7 CBHs
      from social amoeba are surprisingly quite similar in structure and activity to
      the canonical GH7 CBH from the model biomass-degrading fungus T. reesei when
      tested under equivalent conditions (with added CBM-linker domains) on an
      industrially relevant substrate.

PMID- 27037128
TI  - The ED as the primary source of hospital admission for older (but not younger)
      adults.
AB  - INTRODUCTION: The elderly population in the United States is growing. This age
      shift has important implications for emergency departments (EDs), which currently
      account for more than 50% of inpatient hospitalizations. Our objective was to
      compare the percentage of inpatient admissions starting in the ED between elderly
      and younger patients. METHODS: We conducted a retrospective analysis using the
      National Hospital Discharge Survey. Source of admission to the hospital was
      evaluated for years 2003 to 2009. Total admissions from the ED and trends over
      time were analyzed for the following age groups: 22 to 64, 65 to 74, 75 to 84,
      and 85+ years old. Likelihood of having been admitted from the ED was evaluated
      with logistic regression. RESULTS: A total of 1.7 million survey visits
      representing 216 million adult hospitalizations were analyzed. A total of 93
      million (43.2%) were among patients 65 years and older. The ED was the source of
      admission for 57.3% of patients 65 years and older and 44.4% of patients 64 years
      and younger (95% confidence interval difference, 12.97%-13.00%). By 2009, more
      than 75% of nonelective admissions for patients 85 years and older were through
      the ED. There was a linear relationship between age and the ED as the source of
      admission, the odds increasing by 2.9% per year (95% confidence interval, 1.029
      1.029) for each year beyond age 65 years. CONCLUSION: Emergency departments are
      increasingly used as the gateway for hospital admission for older adults. An
      aging US population may increase the effect of this trend, a prospect that should
      be planned for. From the patient perspective, barriers to care contributing to
      the age-based discrepancy in the use of the ED as source of admission should be
      investigated.

PMID- 27037129
TI  - Bystander cardiopulmonary resuscitation training experience and self-efficacy of
      age and gender group: a nationwide community survey.
AB  - BACKGROUND: We hypothesized that recent hands-on practice for cardiopulmonary
      resuscitation (CPR) would be strongly associated with a higher likelihood of self
      efficacy in bystander CPR among laypersons according to age and gender group.
      METHODS: We used the National Korean Community Health Survey database of 228921
      representatively sampled responders from 253 counties in 2012. Laypersons who had
      previous CPR training were eligible. Exposure variables were having had CPR
      training with hands-on practice session with a manikin (Practical-CPR-Training)
      and CPR training within the last 2 years (Recent-CPR-Training). Primary outcome
      was self-efficacy in bystander CPR. Multivariable logistic regression analysis
      was performed. The final model with an interaction term was evaluated to compare
      the effects of CPR training across different age and gender groups. RESULTS: Of
      62425 eligible respondents who have had CPR training, 20213 (32.4%) had Practical
      CPR-Training. Adjusted odds ratios (AORs) for self-efficacy were 4.08 (3.78-4.41)
      in Practical-CPR-Training, 2.61 (2.50-2.73) in male, 1.26 (1.16-1.36) in good
      self-rated health, 1.19 (1.10-1.29) in high school graduate, 1.19 (1.01-1.39) in
      persons living with stroke patients in household, and 1.17 (1.10-1.24) in Recent
      CPR-Training. In interaction models, Practical-CPR-Training showed higher self
      efficacy in all age and gender groups, whereas Recent-CPR-Training was not
      associated with better self-efficacy in elderly group, male (AOR, 0.90 [0.69
      1.18]) and female (AOR, 0.94 [0.72-1.23]). CONCLUSION: Self-efficacy in bystander
      CPR was higher in person with recent CPR training with hands-on practice with a
      manikin.

PMID- 27037130
TI  - Investigation of N-acetylcysteine on contralateral testis tissue injury by
      experimental testicular torsion: long-term effect.
AB  - BACKGROUND: The aim of the study was to investigate long-term effects of N
      acetylcysteine (NAC) on contralateral testes by experimental testicular torsion
      using histopathologic and biochemical parameters. METHODS: Eighteen rats were
      randomized and divided into 3 groups. In group 1, the control group (C),
      laparotomy was performed and the left and right testes were excised 2 months
      later. In group 2, the torsion and detorsion group (T), the torsion was performed
      by rotating the left testis 720 degrees  to clockwise direction, and then 4 hours
      later, detorsion was performed; 2 months later, contralateral testes were
      removed. In group 3, the NAC adding torsion and detorsion group (T+NAC), the
      torsion was performed by rotating the left testis 720 degrees  to clockwise
      direction, and then 4 hours later, detorsion was performed. N-acetylcysteine was
      given intraperitoneally 30 minutes before detorsion and following 5 days after
      detorsion. RESULTS: GPx activities were increased in the T and T+NAC groups
      compared with the control (P = .008 and P = .016, respectively). Seminiferous
      tubule diameter thickness is decreased in the torsion group compared with the
      control group and decreased in the T+NAC group compared with the torsion group (P
      < .05). CONCLUSION: In the long term as implied from the histopathologic
      findings, NAC has beneficial effects against contralateral testis tissue injury
      induced by testicular torsion.

PMID- 27037131
TI  - Platypnea-orthodeoxia syndrome: a simple clinical observation that heralds
      critical but treatable disease.

PMID- 27037132
TI  - Presenting hydrothorax predicts failure of needle aspiration in primary
      spontaneous pneumothorax.
AB  - OBJECTIVE: The objective was to evaluate if existence of hydrothorax in initial
      chest radiograph predicts treatment outcome in patients with primary spontaneous
      pneumothorax who received needle thoracostomy. METHODS: This is a retrospective
      cohort study carried out from January 2011 to August 2014 in 1 public hospital in
      Hong Kong. All consecutive adult patients aged 18years or above who attended the
      emergency department with the diagnosis of primary spontaneous pneumothorax with
      needle aspiration performed as primary treatment were included. Age, smoking
      status, size of pneumothorax, previous history of pneumothorax, aspirated gas
      volume and presence of hydropneumothorax in initial radiograph were included in
      the analysis. The outcome was success or failure of the needle aspiration.
      Logistic regression was used to identify the predicting factors of failure of
      needle aspiration. RESULT: There were a total of 127 patients included. Seventy
      three patients (57.5%) were successfully treated with no recurrence upon
      discharge. Among 54 failure cases, 13 patients (10.2%) failed immediately after
      procedure as evident by chest radiograph and required second treatment. Forty-one
      patients (32.3%) failed upon subsequent chest radiographs. Multivariate logistic
      regression showed factors independently associated with the failure of needle
      aspiration, which included hydropneumothorax in the initial radiograph (odds
      ratio [OR]=4.47 [1.56i12.83], P=.005), previous history of pneumothorax (OR=3.92
      [1.57-9.79], P=.003), and large size of pneumothorax defined as apex-to-cupola
      distance >=5cm (OR=2.75 [1.21-6.26], P=.016). CONCLUSIONS: Hydropneumothorax,
      previous history of pneumothorax, and large size were independent predictors of
      failure of needle aspiration in treatment of primary spontaneous pneumothorax.

PMID- 27037133
TI  - Sniff for a good glottic view.

PMID- 27037134
TI  - Do trauma patients with phencyclidine-positive urine drug screens have increased
      morbidity or mortality?
AB  - BACKGROUND: Phencyclidine (PCP) use is anecdotally associated with agitation and
      injury and is frequently tested for in the setting of trauma. We sought to
      determine characteristics of trauma patients with a PCP-positive urine
      immunoassay drug screen (UDS) and if they had increased levels of care or
      mortality. METHODS: A 5-year retrospective review of a level 1 trauma center's
      trauma registry identified patients with a PCP-positive UDS. This group was then
      compared with 2 randomly selected control groups from the same trauma registry
      which were matched for age and sex but differed in that one had no sEtOH detected
      and a negative UDS (drug-free group) whereas the other had sEtOH or an other-than
      PCP-positive UDS (other-drug group). Subgroup analysis was performed comparing
      PCP-positive patients with undetectable sEtOH with other-drug patients with
      undetectable sEtOH. RESULTS: The registry contained 7770 patients of which 156
      met inclusion criteria. The mean age was 33.4years (range, 19-63), and 77% were
      male (n=121). When compared with the other-drug group, the PCP-positive group had
      significantly lower injury severity score, rates of intensive care unit
      admission, and sEtOH. No difference was seen in vital signs, mechanism of injury,
      ventilator days, intensive care unit days, total hospital days, disposition, or
      mortality between the 3 groups. This remained true even when subgroups with
      negative sEtOH were compared. CONCLUSION: This study suggests that a PCP-positive
      UDS in the setting of trauma is not associated with increased level of care,
      length of stay, or mortality.

PMID- 27037135
TI  - High-impact hepatitis C virus testing for injection drug users in an urban ED.
AB  - OBJECTIVES: We implemented the "High-Impact Testing for Injection Drug Users", or
      the "HIT IDU" initiative, an emergency physician (EP)-based hepatitis C virus
      (HCV) testing program. The objective of this study was to evaluate the outcomes
      of this clinical protocol. METHODS: This was a prospective observational pilot
      study. The HIT IDU initiative encouraged EPs to integrate targeted HCV testing
      into care, with an emphasis on screening all people who inject drugs (PWID).
      Physicians selected the primary indication for HCV testing from a drop-down menu
      integrated into the electronic ordering process. The primary outcome was the
      absolute number and overall proportion of EP-based HCV antibody positive tests,
      further stratified by the indication for testing. RESULTS: Over the 3-month study
      period, 14,253 unique patients were evaluated, and EPs tested 155 patients for
      HCV (1.1%; 95% confidence interval [CI], 0.9%-1.2%), of which 40 (26%, 95% CI,
      19%-33%) were HCV antibody positive. The proportion of HCV antibody positivity by
      testing indication was as follows: PWID 47% (34/73; 95% CI, 35%-59%), patient
      requested test 10% (4/40; 95% CI, 3%-24%), confirm patient report 67% (2/3; 95%
      CI, 9%-99%), liver disease of uncertain etiology 0% (0/3; 95% CI, 0%-71%), and
      other 0% (0/36; 95% CI, 0%-10%). There were 22 patients chronically infected, 19
      had a follow-up appointment arranged, 3 attended their follow-up appointment, and
      1 patient was treated at 1 year of follow-up. CONCLUSIONS: Although the overall
      number of EP-based HCV tests performed was low, high rates of infection were
      identified, particularly among PWID. There were significant challenges with
      linkage to care.

PMID- 27037136
TI  - Bradycardia and hypotension after synthetic cannabinoid use: a case series.

PMID- 27037137
TI  - Attractive ion-ion correlation forces and the dielectric approximation.
AB  - We analyze the classical problem of the interaction between two charged surfaces
      separated by a solution containing neutralizing counter-ions. The focus is on
      obtaining a description where the solvent is treated explicitly rather than
      through a dielectric approximation as is conventionally done. We summarize the
      results of three papers where we have used a Stockmayer fluid model in Monte
      Carlo simulations. It is shown that the attractive ion-ion correlation mechanism
      is also operating when the solvent is described explicitly. There appears an
      oscillatory component to the force, but when this is accounted for, there is a
      semi-quantitative agreement between the continuum model and the model with
      explicit solvent. The properties of the continuum model can be reached in a
      molecular system by making the solvent molecules much smaller than the ions. It
      is demonstrated that having an explicit solvent model makes the analysis of force
      mechanisms more delicate due to the interplay between several different
      microscopic contributions to the force. Finally, it is argued that the agreement
      between the forces calculated using the continuum and the explicit solvent
      models, respectively, has as its basis the circumstance that the force between
      the surfaces is mainly caused by long-range ion-ion interactions, for which the
      dielectric approximation is most adequate. This argument applies equally well to
      an aqueous system as to the Stockmayer fluid.

PMID- 27037138
TI  - A cytoplasmic Cu-Zn superoxide dismutase SOD1 contributes to hyphal growth and
      virulence of Fusarium graminearum.
AB  - Superoxide dismutases (SODs) are scavengers of superoxide radicals, one of the
      main reactive oxygen species (ROS) in the cell. SOD-based ROS scavenging system
      constitutes the frontline defense against intra- and extracellular ROS, but the
      roles of SODs in the important cereal pathogen Fusarium graminearum are not very
      clear. There are five SOD genes in F. graminearum genome, encoding cytoplasmic Cu
      Zn SOD1 and MnSOD3, mitochondrial MnSOD2 and FeSOD4, and extracellular CuSOD5.
      Previous studies reported that the expression of SOD1 increased during infection
      of wheat coleoptiles and florets. In this work we showed that the recombinant
      SOD1 protein had the superoxide dismutase activity in vitro, and that the SOD1
      mRFP fusion protein localized in the cytoplasm of F. graminearum. The Deltasod1
      mutants had slightly reduced hyphal growth and markedly increased sensitivity to
      the intracellular ROS generator menadione. The conidial germination under
      extracellular oxidative stress was significantly delayed in the mutants. Wheat
      floret infection assay showed that the Deltasod1 mutants had a reduced
      pathogenicity. Furthermore, the Deltasod1 mutants had a significant reduction in
      production of deoxynivalenol mycotoxin. Our results indicate that the cytoplasmic
      Cu-Zn SOD1 affects fungal growth probably depending on detoxification of
      intracellular superoxide radicals, and that SOD1-mediated deoxynivalenol
      production contributes to the virulence of F. graminearum in wheat head
      infection.

PMID- 27037139
TI  - Patient-reported impact of spondyloarthritis on work disability and working life:
      the ATLANTIS survey.
AB  - BACKGROUND: The aim was to establish how patients experience the impact of
      spondyloarthritis (SpA) on work disability and working life. METHODS: The survey
      was performed in 17/20 regions in Italy (1 January to 31 March 2013). A multiple
      choice questionnaire was published on the official website of the sponsor - the
      National Association of Rheumatic Patients (ANMAR) - and hard-copies were
      distributed at outpatient clinics for rheumatic patients. RESULTS: Respondents (n
      = 770) were of both sexes (56 % men), educated (62 % at high school or more), of
      working age (75 % aged <=60 years), and affected by SpA. The most common types
      diagnosed were ankylosing spondylitis (AS) (39 %) and psoriatic arthritis (PsA)
      (36 %). Respondents were working full-time (45 %), part-time (8 %) or had retired
      (22 %); 15 % were unemployed (for reasons linked to the disease or for other
      reasons, students or housewives). Patients reported disability (39 %), were
      receiving disability benefits (34 %), were experiencing important limitations
      that were hindering their professional development/career (36 %) and some had to
      change/leave their job or lost it because of SpA (21 %). Employed respondents (n
      = 383) had worked on average 32.2 h in the last 7 days. More hours of work were
      lost over the last 7 days due to SpA (2.39 h vs 1.67 h). The indirect costs of
      the disease amounted to ?106/week for patients reporting well-being/good physical
      conditions/improvement and ?216/week for those reporting permanent impairment.
      CONCLUSIONS: Most patients were in the midst of their productive years and were
      experiencing considerable difficulties in carrying out their job because of the
      disease: half of them reported disability and one third were experiencing
      important limitations in their career perspective.

PMID- 27037141
TI  - Diabetes Treatment as "Homework": Consequences for Household Knowledge and Health
      Practices in Rural Uganda.
AB  - BACKGROUND: Health professionals assign diabetes patients "homework" in that they
      give them instructions on how to manage diabetes, recognizing that most diabetes
      care takes place in the home setting. We studied how homework is practiced and
      whether knowledge and behavioral practices related to diabetes self-management
      diffuse from patients to their housemates. METHOD: This mixed-methods study
      combined quantitative data from a household survey including 90 rural Ugandan
      households (50% had a member with type 2 diabetes [T2D]) with qualitative data
      from health facilities and interviews with 10 patients with T2D. Focus for data
      collection was knowledge and practices related to diabetes homework. A
      generalized mixed model was used to analyze quantitative data, while content
      analysis was used for qualitative data analysis. RESULTS: Patients with T2D
      generally understood the diabetes homework assignments given by health
      professionals and carried out their homework with support from housemates.
      Although adherence to recommended diet was variable, housemates were likely to
      eat a healthier diet than if no patient with T2D lived in the household.
      Knowledge related to diabetes homework diffused from the patients to housemates
      and beyond to neighbors and family living elsewhere. Knowledge about primary
      prevention of T2D was almost absent among health staff, patients, and relatives.
      CONCLUSIONS: Homework practices related to T2D improve diabetes-related knowledge
      and may facilitate healthy eating in nondiabetic housemates. These findings
      suggest that having a chronic disease in the household provides an opportunity to
      improve health in the entire household and address the lack of knowledge about
      prevention of T2D.

PMID- 27037140
TI  - The risks of partner violence following HIV status disclosure, and health service
      responses: narratives of women attending reproductive health services in Kenya.
AB  - INTRODUCTION: For many women living with HIV (WLWH), the disclosure of positive
      status can lead to either an extension of former violence or new conflict
      specifically associated with HIV status disclosure. This study aims to explore
      the following about WLWH: 1. the women's experiences of intimate partner violence
      (IPV) risks following disclosure to their partners; 2. an analysis of the women's
      views on the role of health providers in preventing and addressing IPV,
      especially following HIV disclosure. METHODS: Thirty qualitative interviews were
      conducted with purposively selected WLWH attending clinics in Kenya. Data were
      coded using NVivo 9 and analyzed thematically. RESULTS: Nearly one third of the
      respondents reported experiencing physical and/or emotional violence inflicted by
      their partners following the sero-disclosure, suggesting that HIV status
      disclosure can be a period of heightened risk for partner stigma and abuse, and
      financial withdrawal, and thus should be handled with caution. Sero-concordance
      was protective for emotional and verbal abuse once the partner knew his positive
      status, or knew the woman knew his status. Our results show acceptance of the
      role of the health services in helping prevent and reduce anticipated fear of
      partner stigma and violence as barriers to HIV disclosure. Some of the approaches
      suggested by our respondents included couple counselling, separate counselling
      sessions for men, and facilitated disclosure. The women's narratives illustrate
      the importance of integrating discussions on risks for partner violence and fear
      of disclosure into HIV counselling and testing, helping women develop
      communication skills in how to disclose their status, and reducing fear about
      marital separation and break-up. Women in our study also confirmed the key role
      of preventive health services in reducing blame for HIV transmission and raising
      awareness on HIV as a chronic disease. However, several women reported receiving
      no counselling on safe disclosure of HIV status. CONCLUSION: Integration of
      partner violence identification and care into sexual, reproductive and HIV
      services for WLWH could be a way forward. The health sector can play a preventive
      role by sensitizing providers to the potential risks for partner violence
      following disclosure and ensuring that the women's decision to disclose is fully
      informed and voluntary.

PMID- 27037142
TI  - Glycemic Control in a Clinic-Based Sample of Diabetics in M'Bour Senegal.
AB  - BACKGROUND: Sub-Saharan Africa (SSA) including Senegal is faced with a
      significant and increasing burden of type 2 diabetes. However, little information
      is available about diabetes management among Senegalese diabetics. PURPOSE: The
      current study aims to describe the level of glycemic control among a convenience
      sample of diabetics who receive care at the M'Bour Hospital in M'Bour, Senegal.
      METHODS: A total of 106 type 2 diabetic patients were recruited at the hospital
      complex of M'Bour, Senegal. Linear regression was employed to assess the
      relationship between clinical and sociodemographic factors and Hba1c. RESULTS:
      Only 24.8% of the sample had glycemic control, according to an Hba1c test.
      Participants who were diagnosed earlier were less likely to have diabetes control
      (mean = 7.8 years) compared with those who were diagnosed more recently (mean =
      6.5 years); p< .05. CONCLUSIONS: We found that glycemic control in our sample was
      suboptimal. Length of time with diabetes was one of the key factors related to
      glycemic control. Length of time with diabetes is negatively associated with
      glycemic control. Early diagnosis and early glycemic control are essential to
      long-term glycemic control screening, and early detection for diabetes is
      uncommon given the general lack of health insurance and most people paying out of
      pocket for medical care. In the absence of universal health insurance, public
      health programs that provide blood sugar screenings for high-risk individuals
      would provide preliminary indication of abnormal glucose; however, subsequent
      diagnostic testing and follow-up may still be cost prohibitive.

PMID- 27037143
TI  - Required Actions to Place NCDs in Africa and the Global South High on the World
      Agenda.

PMID- 27037144
TI  - Claim Your Space: Leadership Development as a Research Capacity Building Goal in
      Global Health.
AB  - As the burden of noncommunicable diseases (NCDs) rises in settings with an
      equally high burden of infectious diseases in the Global South, a new sense of
      urgency has developed around research capacity building to promote more effective
      and sustainable public health and health care systems. In 2010, NCDs accounted
      for more than 2.06 million deaths in sub-Saharan Africa. Available evidence
      suggests that the number of people in sub-Saharan Africa with hypertension, a
      major risk factor for cardiovascular diseases, will increase by 68% from 75
      million in 2008 to 126 million in 2025. Furthermore, about 27.5 million people
      currently live with diabetes in Africa, and it is estimated that 49.7 million
      people living with diabetes will reside in Africa by 2030. It is therefore
      necessary to centralize leadership as a key aspect of research capacity building
      and strengthening in the Global South in ways that enables researchers to claim
      their spaces in their own locations. We believe that building capacity for
      transformative leadership in research will lead to the development of effective
      and appropriate responses to the multiple burdens of NCDs that coexist with
      infectious diseases in Africa and the rest of the Global South. 

PMID- 27037145
TI  - Noncommunicable Diseases in Ghana: Does the Theory of Social Gradient in Health
      Hold?
AB  - The theory of social gradient in health posits that individuals with lower
      socioeconomic status (SES) have poorer health outcomes, compared with those in
      higher socioeconomic brackets. Applied to noncommunicable diseases (NCDs), this
      theory has largely been corroborated by studies from the West. However, evidence
      from sub-Saharan Africa are mixed, with those from Ghana conspicuously missing in
      the literature. Using data from the Study on Global Ageing and Adult Health, and
      applying random-effects C log-log models, this study examined the relationship
      between SES and the risks of living with NCDs in Ghana. Results confirmed a
      negative social gradient, as Ghanaians with higher SES were more likely to live
      with NCDs compared with those with low SES. The addition of lifestyle factors
      attenuated the risks of living with NCDs among Ghanaian men and women with higher
      SES. This study underscores the need for policies targeted at specific
      socioeconomic and demographic groups, such as the emerging middle and upper class
      Ghanaians. It is similarly important for interventions to move beyond biomedical
      solutions that put more emphasis on epidemiological risk factors to strategies
      that embrace psychosocial factors as important correlates of cardiovascular
      health. 

PMID- 27037146
TI  - The Global Epidemiologic Transition: Noncommunicable Diseases and Emerging Health
      Risk of Allergic Disease in Sub-Saharan Africa.
AB  - Globally, there has been a shift in the causes of illness and death from
      infectious diseases to noncommunicable diseases. This changing pattern has been
      attributed to the effects of an (ongoing) epidemiologic transition. Although
      researchers have applied epidemiologic transition theory to questions of global
      health, there have been relatively few studies exploring its relevance especially
      in the context of emerging allergic disorders in sub-Saharan Africa (SSA). In
      this article, we address the growing burden of noncommunicable diseases in sub
      Saharan Africa through the lens of epidemiologic transition theory. After a brief
      review of the literature on the evolution of the epidemiologic transition with a
      particular emphasis on sub-Saharan Africa, we discuss existing frameworks
      designed to help inform our understanding of changing health trends in the
      developing world. We subsequently propose a framework that privileges "place" as
      a key construct informing our understanding. In so doing, we use the example of
      allergic disease, one of the fastest growing chronic conditions in most parts of
      the world. 

PMID- 27037147
TI  - Ideal Body Size as a Mediator for the Gender-Specific Association Between
      Socioeconomic Status and Body Mass Index: Evidence From an Upper-Middle-Income
      Country in the African Region.
AB  - BACKGROUND: While obesity continues to rise globally, the associations between
      body size, gender, and socioeconomic status (SES) seem to vary in different
      populations, and little is known on the contribution of perceived ideal body size
      in the social disparity of obesity in African countries. PURPOSE: We examined the
      gender and socioeconomic patterns of body mass index (BMI) and perceived ideal
      body size in the Seychelles, a middle-income small island state in the African
      region. We also assessed the potential role of perceived ideal body size as a
      mediator for the gender-specific association between SES and BMI. METHOD: A
      population-based survey of 1,240 adults aged 25 to 64 years conducted in December
      2013. Participants' BMI was calculated based on measured weight and height; ideal
      body size was assessed using a nine-silhouette instrument. Three SES indicators
      were considered: income, education, and occupation. RESULTS: BMI and perceived
      ideal body size were both higher among men of higher versus lower SES (p< .001)
      but lower among women of higher versus lower SES (p< .001), irrespective of the
      SES indicator used. Multivariate analysis showed a strong and direct association
      between perceived ideal body size and BMI in both men and women (p< .001) and was
      consistent with a potential mediating role of perceived ideal body size in the
      gender-specific associations between SES and BMI. CONCLUSION: Our study
      emphasizes the importance of gender and socioeconomic differences in BMI and
      ideal body size and suggests that public health interventions that promote
      perception of healthy weight could help mitigate SES-related disparities in BMI.

PMID- 27037148
TI  - Noncommunicable Diseases in Africa and the Global South.

PMID- 27037149
TI  - Implementation of Policies and Strategies for Control of Noncommunicable Diseases
      in Malawi: Challenges and Opportunities.
AB  - Malawi is a Sub-Saharan African country experiencing the epidemiological
      transition from predominantly infectious to noncommunicable diseases (NCDs) with
      dramatically increasing prevalence of lifestyle-related diseases such as obesity,
      hypertension, and diabetes. Malawi's 2011-2016 Health Sector Strategic Plan
      included NCDs, and an NCD Control Program was established with subsequent
      development of a National Action Plan for prevention and management of NCDs
      launched in 2013. The current study was designed to identify gaps in
      implementation of NCD control program policies and action plan strategies by
      describing current efforts toward prevention and management of NCDs in Malawi
      with emphasis on challenges and opportunities. Semistructured questionnaires were
      used to collect quantitative and qualitative data from Malawi Ministry of Health
      personnel (senior officers, service providers, health education officers, and
      nutritionists) in 10 health districts and 3 central hospitals. Frequencies were
      generated for quantitative data. Qualitative data were used to generate themes
      and most common responses. Results showed that current services focus on facility
      based NCD screening and clinical services rather than active screening,
      prevention, and community awareness and outreach, although respondents emphasized
      the importance of prevention, lifestyle education, and community outreach.
      Respondents indicated inadequate resources for NCD services including financial
      capital, human resources, equipment and supplies, and transportation. While
      Malawi has begun to address NCDs, policy and practice implications include (a)
      better integration of services within the existing infrastructure with emphasis
      on capacity building; (b) greater implementation of planned NCD activities; (c) a
      stronger, more comprehensive data management system; and (d) innovative funding
      solutions. 

PMID- 27037150
TI  - Reducing the Role of the Food, Tobacco, and Alcohol Industries in Noncommunicable
      Disease Risk in South Africa.
AB  - Noncommunicable diseases (NCDs) impose a growing burden on the health, economy,
      and development of South Africa. According to the World Health Organization, four
      risk factors, tobacco use, alcohol consumption, unhealthy diets, and physical
      inactivity, account for a significant proportion of major NCDs. We analyze the
      role of tobacco, alcohol, and food corporations in promoting NCD risk and
      unhealthy lifestyles in South Africa and in exacerbating inequities in NCD
      distribution among populations. Through their business practices such as product
      design, marketing, retail distribution, and pricing and their business practices
      such as lobbying, public relations, philanthropy, and sponsored research,
      national and transnational corporations in South Africa shape the social and
      physical environments that structure opportunities for NCD risk behavior. Since
      the election of a democratic government in 1994, the South African government and
      civil society groups have used regulation, public education, health services, and
      community mobilization to modify corporate practices that increase NCD risk. By
      expanding the practice of health education to include activities that seek to
      modify the practices of corporations as well as individuals, South Africa can
      reduce the growing burden of NCDs. 

PMID- 27037151
TI  - Tackling Noncommunicable Diseases in Africa: Caveat Lector.
AB  - Noncommunicable disease (NCD), principally cardiovascular diseases, cancer,
      chronic lung disease, and diabetes, constitutes the major cause of death
      worldwide. Evidence of a continuing increase in the global burden of these
      diseases has generated recent urgent calls for global action to tackle and reduce
      related death and disability. Because the majority of NCD deaths occur in low-
      and middle-income countries, increased attention has been focused on this group
      of countries. However, in sub-Saharan Africa, where all countries are members of
      the low- and middle-income grouping, NCDs are not the leading causes of death or
      potential life years lost. Thus, strategies to tackle NCDs in sub-Saharan Africa
      are best conceived and executed in alignment with existing strategies for the
      prevention, treatment, and control of the actual leading causes of death in this
      region. This commentary addresses caveats to be considered as strategies are
      developed to tackle NCDs in sub-Saharan Africa as part of the global effort to
      prevent, treat, and control NCDs. 

PMID- 27037152
TI  - Stroke Investigative Research and Education Network: Community Engagement and
      Outreach Within Phenomics Core.
AB  - Stroke is the leading cause of neurological hospital admissions in sub-Saharan
      Africa (SSA) and the second leading cause of death globally. The Stroke
      Investigative Research and Education Network seeks to comprehensively
      characterize the genomic, sociocultural, economic, and behavioral risk factors
      for stroke and to build effective teams for research to address and decrease the
      burden of stroke and other noncommunicable diseases in SSA. One of the first
      steps to address this goal is to effectively engage the communities that suffer
      the high burden of disease. The purpose of this article is to describe plans to
      elucidate information about knowledge, attitudes, beliefs, and practices about
      stroke and genomics from patients, caregivers, and local leaders, to recruit
      participation in research activities and dissemination of ongoing results, as
      well as to facilitate research uptake and impact within the broader communities
      of scientists, health professionals, policy makers, and others. We describe the
      (a) study sites and their communities; (b) plans for community advisory boards,
      focus groups, and surveys; (c) methods for data management in REDCap database;
      (d) analyses of qualitative data; (e) evaluation of community and public
      engagement across multiple sites and research teams in SSA and the United States;
      (f) use of RE-AIM for presentation of evaluation data; and (g) community
      indicators of success. This is the first of its kind public outreach engagement
      initiative to evaluate stroke and genomics in SSA, and has implications as a
      model for assessment in other high-stroke risk populations.

PMID- 27037153
TI  - Cognitive Impairment Among the Aging Population in a Community in Southwest
      Nigeria.
AB  - BACKGROUND: Vascular risk models can be quite informative in assisting the
      clinician to make a prediction of an individual's risk of cognitive impairment.
      Thus, a simple marker is a priority for low-capacity settings. This study
      examines the association of selected simple to deploy vascular markers with
      cognitive impairment in an elderly population. METHOD: This cross-sectional study
      assessed the cognitive functions of older persons 65 years and older in southwest
      Nigeria. Vascular parameters and risk factors were also measured. Analysis was
      done using SPSS, and logistic regression was used to explore the association
      between cognitive impairment and certain vascular risk factors such as elevated
      blood pressure, diabetes, and pulse pressure. RESULTS: The study population
      comprised 623 participants (29.1% men) with mean age 73 +/- 8.9 years. Having
      mean arterial pressure (MAP) and pulse pressure in the fourth quartiles (27% and
      29.9%, respectively) was significantly associated with cognitive impairment (p=
      .001,p< .001). Predicted cardiovascular risks of 10% or more was significantly
      associated with cognitive impairment (p< .001). After adjusting for age, gender,
      educational level, and years of smoking, those with MAP in the fourth quartile
      were up to 3 times more likely to have cognitive impairment compared to those
      within the first quartile. CONCLUSION: Our study demonstrated that among elderly
      Nigerians, MAPs of 114 mmHg and more was an independent predictor of cognitive
      impairment. This is a simple measure that is available in low-capacity areas.

PMID- 27037154
TI  - The registration of clinical trials: Necessary and forced.

PMID- 27037155
TI  - Erratum to: Erythropoietin improves long-term neurological outcome in acute
      ischemic stroke patients: a randomized, prospective, placebo-controlled clinical
      trial.

PMID- 27037156
TI  - A new approach to the management of ovarian endometrioma to prevent tissue damage
      and recurrence.
AB  - Management of ovarian endometrioma is a matter of debate between those advocating
      early treatment and those believing that cysts less than 3 cm in diameter should
      not be submitted to surgery. To explore a new approach to its management capable
      of preserving future fertility, the molecular pathology of ovarian endometrioma
      is reviewed and mechanisms by which the endometrioma progressively affects the
      ovary during reproductive life are summarized. The scope of new therapeutic
      modalities includes restoring the progesterone receptor ratio using progestin or
      progesterone receptor modulators and decreasing local oestrogen production
      through an aromatase inhibitor. In addition, free radical production can be
      blocked by antioxidants and the autophagic process by increasing apoptosis.
      Finally, metalloproteinases and relaxin activity, as well as the inflammatory
      process can be controlled. Many of these pharmacological treatments lend
      themselves to local administration and can be applied through intracystic drug
      administration; in fact, the intracystic route has already been tried with
      recombinant interleukin-2, methotrexate and ethanol; the latter to obtain
      sclerotization. Specifically, it is proposed that endometrial growth in the
      endometrioma is suppressed by intra-cystic application of synthetic progestins,
      such as levonorgestrel or danazol, selective progesterone receptor modulators,
      such as mifepristone, ulipristal or asoprisnil, without affecting ovarian
      activity. 

PMID- 27037157
TI  - Microenvironment and autophagy cross-talk: Implications in cancer therapy.
AB  - There are many ongoing clinical trials to validate tumour microenvironment or
      autophagic pathway components as targets for anticancer therapies. Different
      components of the tumour microenvironment play important roles in tumour cell
      responses, directly affecting malignant transformation, drug resistance and
      metastasis. Autophagy is also related to chemotherapy responses by inducing
      tumour cell death or survival. Thus, the autophagy pathway may act as
      oncosuppressor, in addition to protecting cells from chemotherapy. The cross-talk
      between the microenvironment and autophagy is very complex and poorly understood.
      In a recent study using a three-dimensional (3D) cell culture model, the well
      documented chemotherapy-mediated activation of autophagy was impaired in breast
      cancer cells, suggesting a context-dependent outcome for autophagy modulators,
      under the control of the p53 protein. A deeper understanding of this
      microenvironment/autophagy interplay may provide important clues for identifying
      differences in the tumour cell signalling network from in vitro basic research
      studies to the actual clinical context. In this work, we summarize the role of
      the microenvironment and autophagy in physiological and tumourigenic conditions,
      their interactions, and the challenges related to the use of drugs that target
      these pathways in cancer treatment protocols, emphasizing the potential use of 3D
      cell culture models in preclinical studies.

PMID- 27037158
TI  - Two-dimensional MoS2: A promising building block for biosensors.
AB  - Recently, two-dimensional (2D) layered nanomaterials have trigged intensive
      interest due to the intriguing physicochemical properties that stem from a
      quantum size effect connected with their ultra-thin structure. In particular, 2D
      molybdenum disulfide (MoS2), as an emerging class of stable inorganic graphene
      analogs with intrinsic finite bandgap, would possibly complement or even surpass
      graphene in electronics and optoelectronics fields. In this review, we first
      discuss the historical development of ultrathin 2D nanomaterials. Then, we are
      concerned with 2D MoS2 including its structure-property relationships, synthesis
      methods, characterization for the layer thickness, and biosensor applications
      over the past five years. Thereinto, we are highlighting recent advances in 2D
      MoS2-based biosensors, especially emphasize the preparation of sensing elements,
      roles of 2D MoS2, and assay strategies. Finally, on the basis of the current
      achievements on 2D MoS2 and other ultrathin layered nanomaterials, perspectives
      on the challenges and opportunities for the exploration of 2D MoS2-based
      biosensors are put forward.

PMID- 27037159
TI  - Surface Plasmon Resonance based sensing of lysozyme in serum on Micrococcus
      lysodeikticus-modified graphene oxide surfaces.
AB  - Lysozyme is an enzyme found in biological fluids, which is upregulated in
      leukemia, renal diseases as well as in a number of inflammatory gastrointestinal
      diseases. We present here the development of a novel lysozyme sensing concept
      based on the use of Micrococcus lysodeikticus whole cells adsorbed on graphene
      oxide (GO)-coated Surface Plasmon Resonance (SPR) interfaces. M. lysodeikticus is
      a typical enzymatic substrate for lysozyme. Unlike previously reported sensors
      which are based on the detection of lysozyme through bioaffinity interactions,
      the bioactivity of lysozyme will be used here for sensing purposes. Upon exposure
      to lysozyme containing serum, the integrity of the bacterial cell wall is
      affected and the cells detach from the GO based interfaces, causing a
      characteristic decrease in the SPR signal. This allows sensing the presence of
      clinically relevant concentrations of lysozyme in undiluted serum samples.

PMID- 27037160
TI  - Corrigendum to "Implementation of geriatric assessment-based recommendations in
      older patients with cancer: A multicenter prospective study" [J. Geriatr. Oncol.
      6 (2015) 401-410].
AB  - The authors regret: A calculation error was corrected in Table 3. As mentioned
      under the table, the percentage of patients under 'Baseline' was calculated from
      the total no. of patients with geriatric recommendations data (n = 932 pts). This
      was mistakenly calculated from the number of patients with available GA data (n =
      979). Percentages have been recalculated. The corrected table is reproduced here
      (Table 3). We emphasize that these percentages are not mentioned in the text of
      the paper nor do they change any of the conclusions. The authors would like to
      apologize for any inconvenience caused.

PMID- 27037161
TI  - Educating jurors about eyewitness testimony in criminal cases with circumstantial
      and forensic evidence.
AB  - We investigated whether the Interview-Identification-Eyewitness factors (I-I-Eye)
      educational aid could sensitize mock jurors to the quality of eyewitness evidence
      in criminal cases which also contained circumstantial and forensic evidence.
      After participants were randomly assigned to read either the I-I-Eye or a control
      aid, they read a trial transcript containing either strong or weak eyewitness
      evidence. The police consistently followed scientific interviewing and
      identification procedures in the strong case, but not in the weak case. In two
      experiments, the I-I-Eye participants were approximately three times more likely
      than the control participants to enter guilty verdicts in the strong case than in
      the weak case. Thus the I-I-Eye educational aid increased participants'
      sensitivity to the eyewitness evidence. The I-I-Eye method provides a valuable
      analytical framework for evaluating eyewitness evidence in criminal cases. It may
      be capable of becoming "a standard feature for criminal cases" with eyewitness
      evidence.

PMID- 27037162
TI  - Unlocking the doors to Canadian older inmate mental health data: Rates and
      potential legal responses.
AB  - This article is based on a quantitative study investigating the quality of life
      of older Canadian prisoners. For this study, social science methodology was used
      to answer certain legal questions, such as: what are the mental health issues of
      older male offenders and how are these needs influencing the exercise of their
      legal rights? Are institutions prepared to deal with the increased needs of older
      offenders? If no, is this an infringement of this group's rights? In this
      article, the mental health problems of older offenders are first outlined.
      Second, the legal, policy, and institutional limitations in responding to these
      problems are described. Based on these findings, it is maintained that a change
      in the treatment of older offenders is needed. Third, statutory and
      constitutional challenges are explored. If change does not come voluntarily, it
      is the duty of the courts to have a flexible and open-minded approach toward
      different actions that challenge the current prison regime.

PMID- 27037163
TI  - Perioperative Surgical Home-An Innovative Concept.

PMID- 27037165
TI  - Comparing Three Methods for Dilution Accuracy of Intravenous Preparations.
AB  - PURPOSE: Dilutions of intravenous medications may be inaccurate. The mixing
      technique may be a crucial factor. DESIGN: Three factors of dilution were tested:
      volume for dilution (large vs small), method for mixing (shaking vs inversion),
      and number of maneuvers (3 times vs 10). METHODS: Dilutions of glucose in saline
      solution were made by nurses, after a random factorial plan. The judgment
      criteria were the comparison between measured (Cmes) and expected (Cexp)
      concentration. FINDING: Cmes (n = 40) ranged from 89.5% to 123.6% of Cexp and was
      more accurate when made with a large volume (98.4% of Cexp vs 106.5%) and when
      mixed by inversion (100.6% of Cexp vs 104.6%). CONCLUSIONS: Inversion rather than
      shaking and dilution in a large volume is a simple procedure for bedside
      medication preparation that allows better accuracy. The 3 versus 10 mixing
      procedures resulted in the same accuracy, which may be important for these time
      consuming procedures. These results should be confirmed in clinical situations.

PMID- 27037166
TI  - Exploring the Impact of Intraoperative Interventions for Pain and Anxiety
      Management During Local Anesthetic Surgery-A Systematic Review and Meta-Analysis.
AB  - PURPOSE: To compare the effectiveness of audiovisual and relaxation-based
      intraoperative interventions for their impact on intraoperative pain and anxiety.
      DESIGN: Systematic review and meta-analysis. METHODS: The following databases
      were searched for articles published between 1990 and January 2014: MEDLINE,
      PsychINFO, CINAHL, and Web of Science. Twenty randomized trials meeting the
      following inclusion criteria were included; adult participants undergoing
      elective outpatient surgery under local anesthetic using a form of distraction
      based intraoperative intervention for the management of anxiety and pain.
      FINDING: Thirty percent of studies reviewed found that intraoperative
      interventions improved patient experience in comparison to treatment as usual,
      20% of studies were inconclusive, and 50% of studies found that interventions
      during surgery provided no benefit. CONCLUSIONS: Both relaxation-based and
      audiovisual interventions were found to be efficacious for pain and anxiety
      management during surgery under local anesthetic. This review indicates that
      relaxation-based interventions could be more effective than audiovisual
      interventions for managing intraoperative anxiety.

PMID- 27037167
TI  - An Educational Plan for Nursing Staff in the Procedural Treatment Unit of the
      Sulpizio Cardiovascular Center.
AB  - Professional education for health practitioners is a continuum which commences
      with the first year professional school until the cessation of a professional
      career. This article draws on the theories and models developed by experts in
      curriculum design, teaching, and learning evaluation to better understand the
      intricacies and challenges of instructional design. Selected models, in
      particular Malcolm Knowles and the World Health Organization report served as a
      compass and benchmark to illuminate, guide, and evaluate the impact, process,
      contents, and outcomes of an educational program for the stakeholders. The aim of
      this educational program is to ensure that learners develop the knowledge,
      skills, and attitudes to deliver competent and quality patient-centered care.
      Multimodal teaching strategies are essential to meet the diverse needs of staff.
      Utilization of technology such as intranet and mobile applications helps to
      deliver educational content in a cost-effective manner. Program evaluation
      determines the effectiveness of teaching and helps to define ongoing needs of
      staff. 

PMID- 27037168
TI  - The Operating Room Experiences of Nursing Students: A Focus Group Study.
AB  - PURPOSE: The purpose of this study was to evaluate operating room (OR)
      experiences of student nurses. DESIGN: The focus group interview from qualitative
      research methods was used. METHODS: This study was carried out between February
      and March 2011 in an OR practice at a university school of nursing. The grounded
      theory method was used to collect and analyze semistructured interview.
      Interviews were held with a total of 26 students in three focus group interviews.
      Each interview was tape recorded and was supported by taking notes. The
      audiotapes were listened and relistened by the researchers and transcribed.
      FINDINGS: Four themes were determined as a result of this study. These are
      information, determination of career preference, period of internship and/or
      rotation, and fear and/or anxiety. CONCLUSIONS: The students stated that the
      period of OR practice was insufficient, the opportunities for being able to
      implement were limited, they mostly observed, and they experienced feelings of
      being alone and fear in the OR. Despite all of these, the students stated that
      the OR practice provided a major contribution to their education and was
      effective in the determination of their career preferences after graduation.

PMID- 27037169
TI  - NaHCO3-Buffered Lidocaine Gel for Outpatient Rigid Cystoscopy in Men.
AB  - PURPOSE: The purpose of this study was to explore the effect of NaHCO3-buffered
      lidocaine gel as a topical anesthetic agent for pain relief for rigid cystoscopy.
      DESIGN: Prospective randomized controlled trial. METHODS: ASA I-II male patients
      undergoing rigid cystoscopy randomly received 10 mL 2% Carbocaine lidocaine gel
      with 1 mL 0.9% saline (group 1) or 1 mL 5% NaHCO3 solution (group 2). After 3
      minutes exposure, the cystoscope was inserted into the urethra. On receiving the
      gel, cystoscope insertion, and intravesical observation, pain score was recorded
      using the visual analog scale. FINDINGS: The gel pH with or without NaHCO3 was
      7.20 and 6.41, respectively. The concentration of soluble lidocaine in the gel
      was stable for 24 hours or more. The visual analog scale score in group 2 was
      significantly lower (1.3 +/- 0.9) than in group 1 (5.28 +/- 1.99). No adverse
      effects were recorded. CONCLUSION: Alkalized lidocaine gel resulted in successful
      analgesia for rigid cystoscopy in men without adverse effects.

PMID- 27037170
TI  - Reducing the Incidence of Postoperative Nausea and Vomiting Begins With Risk
      Screening: An Evaluation of the Evidence.
AB  - Postoperative nausea and vomiting (PONV) is a daily concern for patients and
      perianesthesia nurses. PONV is experienced by approximately one third of all
      surgical patients. Identification of patients at risk for PONV through
      preoperative risk assessment is an effective means in reducing the incidence of
      PONV. Perianesthesia nurses are positioned to implement such risk assessments by
      using simplified risk scores to identify moderate to high-risk patients. Risk
      assessment allows for facilitation of targeted prophylaxis which positively
      impacts the patients' surgical outcome and experience. Targeted prophylaxis is
      efficacious in reducing the institutional incidence of PONV which decreases
      resource utilization and cost. The perianesthesia nurse is the crucial component
      in minimizing the PONV in the post-surgical patient. This evaluation of the
      evidence reveals that preoperative PONV risk screening leads to decreased
      incidence of PONV for the surgical patient, improves patient satisfaction and
      reduces postoperative complications. 

PMID- 27037171
TI  - Recovery After ICU Discharge: Post-Intensive Care Syndrome.

PMID- 27037172
TI  - The Art of Giving Feedback.

PMID- 27037173
TI  - Thinking About Patient Safety: Cognitive Errors.

PMID- 27037174
TI  - Enhanced Recovery After Surgery.

PMID- 27037175
TI  - Is Anesthesia Safe for My Child?

PMID- 27037178
TI  - Patient Acuity in Perianesthesia Practice: Guest Editorial.

PMID- 27037179
TI  - Analysis and natural history of pituitary incidentalomas.
AB  - OBJECTIVES: Pituitary incidentalomas (PI) are frequently found on brain imaging.
      Despite their high prevalence, little is known about their long-term natural
      history and there are limited guidelines on how to monitor them. METHODS: We
      conducted a retrospective study to compare epidemiological characteristics at
      presentation and the natural history of PI in population-based vs referral-based
      registries from two tertiary-care referral centers in Canada. RESULTS: A total of
      328 patients with PI were included, of whom 73% had pituitary adenomas (PA) and
      27% had non-pituitary sellar masses. The commonest indications for imaging were
      headache (28%), dizziness (12%) and stroke/transient ischemic attack (TIA) (9%).
      There was a slight female preponderance (52%) with a median age of 55 years at
      diagnosis; 71% presented as macroadenomas (>10mm). Of PA, 25% were functioning
      tumors and at presentation 36% of patients had evidence of secondary hormonal
      deficiency (SHD). Of the total cohort, 68% were treated medically or
      conservatively whereas 32% required surgery. Most tumors (87% in non-surgery and
      68% in post-surgery group) remained stable during follow-up. Similarly, 84% of
      patients in the non-surgery and 73% in the surgery group did not develop
      additional SHD during follow-up. The diagnosis of non-functioning adenoma was a
      risk factor for tumor enlargement and a change in SHD status was associated with
      a change in tumor size. CONCLUSIONS: Our data suggest that most PI seen in
      tertiary-care referral centers present as macroadenomas and may frequently be
      functional, often requiring medical or surgical intervention.

PMID- 27037180
TI  - Exploring the overlap between multiple sclerosis, tumefactive demyelination and
      Balo's concentric sclerosis.
AB  - The availability of magnetic resonance imaging (MRI) has led to increasing
      recognition that multiple sclerosis (MS), tumefactive demyelination (TD) and
      Balo's concentric sclerosis (BCS) share many overlapping features. Balo-like
      lesions, which exhibit limited features of BCS, may represent an intermediate
      between BCS and typical MS demyelination. Lesions labeled as tumefactive are
      typically larger, but otherwise have much in common with conventional MS lesions,
      and TD and BCS lesions can also overlap. In this article, we explore the
      similarities between typical MS, TD and BCS cases, and reflect on the potential
      insights that intermediate or overlapping phenotypes may contribute towards an
      understanding of MS immunopathogenesis, and question whether these atypical forms
      of demyelination should be classified as separate demyelinating diseases, as
      different lesional manifestations of demyelination of any cause or as part of a
      spectrum with conventional MS.

PMID- 27037181
TI  - A prospective cohort study of vitamin D in optic neuritis recovery.
AB  - BACKGROUND: Vitamin D sufficiency is associated with better inflammatory outcomes
      in multiple sclerosis (MS). We hypothesize that it is also associated with better
      long-term neurodegenerative measures. OBJECTIVES: To show that vitamin D
      sufficient patients (25-hydroxy vitamin D (25(OH)D) > 80 nmol/L) have better
      optical coherence tomography (OCT) neuroaxonal measures of ganglion cell layer
      (GCL) and retinal nerve fiber layer (RNFL) thickness after optic neuritis.
      METHODS: In this prospective cohort study, acute optic neuritis patients
      underwent OCT and serum 25(OH)D assessments at baseline and at month 6, with
      comparisons between vitamin D sufficient and insufficient patients, and men and
      women. Potential confounding variables were evaluated. RESULTS: Of 49 enrolled,
      36 had complete, analyzable data. At baseline, vitamin D insufficiency was
      associated with greater RNFL thickness (134.3 vs. 95.2 um; p = 0.003) in affected
      eyes. At month 6, insufficient patients had greater GCL thinning (GCL inter-eye
      difference: 14.2 vs. 4.0 um, p = 0.008). Men had greater RNFL and GCL thinning
      than women (GCL: 61.2 vs. 69.6 um, p = 0.036). CONCLUSION: Acutely, in optic
      neuritis, RNFL thickness is increased with vitamin D insufficiency. Chronically,
      neuronal, and possibly axonal loss are associated with vitamin D insufficiency
      and male gender, suggesting vitamin D and female gender may confer
      neuroprotection in optic neuritis, and possibly, central nervous system (CNS)
      inflammatory disease.

PMID- 27037182
TI  - Immunological and pathological characterization of fatal rebound MS activity
      following natalizumab withdrawal.
AB  - BACKGROUND: Severe rebound multiple sclerosis (MS) activity is a life-threatening
      complication of natalizumab (NTZ) withdrawal, for which pathogenesis and
      treatment are still unclear. We report the immunological and pathological
      characterization of a case of central nervous system (CNS) inflammatory
      demyelination after NTZ discontinuation. OBJECTIVE: To understand the
      pathophysiology of this neuroinflammatory condition. METHODS: Antemortem blood
      and cerebrospinal fluid (CSF) analysis was compared with postmortem pathological
      studies, as well as with novel flow cytometry characterization of immune cells
      isolated from the CNS parenchyma. RESULTS: Pathological analysis of the brain
      revealed the presence of innumerable active inflammatory demyelinating lesions
      typical of immunopathological pattern II. Monocytes/macrophages and B cells were
      enriched in the CNS parenchyma compared to the CSF. Numerous plasma cells were
      present in the lesions, but CD8 T lymphocytes were predominant in the parenchyma,
      as opposed to CD4 in the CSF. CNS-infiltrating lymphocytes expressed high levels
      of adhesion molecules, granzyme B (GzB), interferon-gamma (IFN-gamma), and
      interleukin (IL)-17. CONCLUSIONS: Our results underline the differences in immune
      cell populations between the CSF and the CNS parenchyma, and suggest that
      aggressive immunosuppressive therapy targeting both T and B lymphocytes is
      warranted to control the overwhelming CNS inflammation.

PMID- 27037183
TI  - Clostridium butyricum attenuates cerebral ischemia/reperfusion injury in diabetic
      mice via modulation of gut microbiota.
AB  - Diabetes is known to exacerbate cerebral ischemia/reperfusion (I/R) injury. Here,
      we investigated the effects of Clostridium butyricum on cerebral I/R injury in
      the diabetic mice subjected to 30min of bilateral common carotid arteries
      occlusion (BCCAO). The cognitive impairment, the blood glucose level, neuronal
      injury, apoptosis, and expressions of Akt, phospho-Akt (p-Akt), and caspase-3
      level were assessed. Meanwhile, the changes of gut microbiota in composition and
      diversity in the colonic feces were evaluated. Our results showed that diabetic
      mice subjected to BCCAO exhibited worsened cognitive impairment, cell damage and
      apoptosis. These were all attenuated by C. butyricum. Moreover, C. butyricum
      reversed cerebral I/R induced decreases in p-Akt expression and increases in
      caspase-3 expression, leading to inhibiting neuronal apoptosis. C. butyricum
      partly restored cerebral I/R induced decreases of fecal microbiota diversity,
      changes of fecal microbiota composition. Together, these findings highlight the
      important role of bacteria in the bidirectional communication of the gut-brain
      axis and suggest that certain probiotics might prove to be useful therapeutic
      adjuncts in cerebral I/R injury with diabetes.

PMID- 27037184
TI  - Protein aggregation and ER stress.
AB  - Protein aggregation is a common feature of the protein misfolding or
      conformational diseases, among them most of the neurodegenerative diseases. These
      disorders are a major scourge, with scarce if any effective therapies at present.
      Recent research has identified ER stress as a major mechanism implicated in
      cytotoxicity in these diseases. Whether amyloid-beta or tau in Alzheimer's, alpha
      synuclein in Parkinson's, huntingtin in Huntington's disease or other aggregation
      prone proteins in many other neurodegenerative diseases, there is a shared
      pathway of oligomerization and aggregation into amyloid fibrils. There is
      increasing evidence in recent years that the toxic species, and those that evoke
      ER stress, are the intermediate oligomeric forms and not the final amyloid
      aggregates. This review focuses on recent findings on the mechanisms and
      importance of the development of ER stress upon protein aggregation, especially
      in neurodegenerative diseases, and possible therapeutic approaches that are being
      examined. This article is part of a Special Issue entitled SI:ER stress.

PMID- 27037185
TI  - Intractable problems require novel solutions: it's time to get serious about
      developing a gonorrhoea vaccine.

PMID- 27037186
TI  - Can Transcranial Direct Current Stimulation Augment Extinction of Conditioned
      Fear?
AB  - BACKGROUND: Exposure-based therapy parallels extinction learning of conditioned
      fear. Prior research points to the ventromedial prefrontal cortex as a potential
      site for the consolidation of extinction learning and subsequent retention of
      extinction memory. OBJECTIVE/HYPOTHESIS: The present study aimed to evaluate
      whether the application of non-invasive transcranial direct current stimulation
      (tDCS) during extinction learning enhances late extinction and early recall in
      human participants. METHODS: Forty-four healthy volunteers completed a 2-day
      Pavlovian fear conditioning, extinction, and recall paradigm while skin
      conductance activity was continuously measured. Twenty-six participants received
      2 mA anodal tDCS over EEG coordinate AF3 during extinction of a first conditioned
      stimulus. The remaining 18 participants received similar tDCS during extinction
      of a second conditioned stimulus. Sham stimulation was applied for the balance of
      extinction trials in both groups. Normalized skin conductance changes were
      analyzed using linear mixed models to evaluate effects of tDCS over late
      extinction and early recall trials. RESULTS: We observed a significant
      interaction between timing of tDCS during extinction blocks and changes in skin
      conductance reactivity over late extinction trials. These data indicate that tDCS
      was associated with accelerated late extinction learning of a second conditioned
      stimulus after tDCS was combined with extinction learning of a previous
      conditioned stimulus. No significant effects of tDCS timing were observed on
      early extinction recall. CONCLUSIONS: Results could be explained by an anxiolytic
      aftereffect of tDCS and extend previous studies on tDCS-induced modulation of
      fear and threat related learning processes. These findings support further
      exploration of the clinical use of tDCS.

PMID- 27037187
TI  - Hydroxychloroquine attenuates cigarette smoke induced autophagic signaling in the
      mouse ovary.
AB  - We previously demonstrated that Cigarette Smoke (CS) induces autophagy in the
      ovary. Therefore we aimed to determine if chloroquine (CQ) could inhibit CS
      induced autophagy in the ovary. Eight week old mice were implanted with CQ
      pellets; 0, 25, and 50mg CQ/kg. Half of the animals in each group were exposed to
      room air and the other half were exposed to CS twice daily for 8 weeks. Ovaries
      were harvested for electron microscopy, gene and protein expression analysis.
      There was a significant increase in the production of autophagosomes in granulosa
      cells of mice exposed to CS (p=0.0297). However 25 and 50mg/kg CQ treatment
      significantly decreased the CS-induced autophagosomes (p=0.0505; p=0.0065) and
      attenuated the effects of CS on LC3B and BECN1 expression. In summary, this
      suggests that CQ attenuates CS-induced autophagy in the ovary and that ovarian
      protection from toxic insult is potentially feasible.

PMID- 27037188
TI  - Toxic effects of prenatal exposure to alcohol, tobacco and other drugs.
AB  - Tobacco, alcohol, cannabis and cocaine are the most consumed psychoactive drugs
      throughout the population. Prenatal exposure to these drugs could alter normal
      foetal development and could threaten future welfare. The main changes observed
      in prenatal exposure to tobacco are caused by nicotine and carbon monoxide, which
      can impede nutrient and oxygen exchange between mother and foetus, restricting
      foetal growth. Memory, learning processes, hearing and behaviour can also be
      affected. Alcohol may cause physical and cognitive alterations in prenatally
      exposed infants, fundamentally caused by altered NMDAR and GABAR activity.
      Tetrahydrocannabinol, the psychoactive compound of cannabis, is capable of
      activating CB1R, inducing connectivity deficits during the foetal brain
      development. This fact could be linked to behavioural and cognitive deficits.
      Many of the effects from prenatal cocaine exposure are caused by altered cell
      proliferation, migration, differentiation and dendritic growth processes. Cocaine
      causes long term behavioural and cognitive alterations and also affects the
      uteroplacental unit.

PMID- 27037189
TI  - Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific
      Regulatory T Cells.
AB  - Although antigen recognition mediated by the T cell receptor (TCR) influences
      many facets of Foxp3(+) regulatory T (Treg) cell biology, including development
      and function, the cell types that present antigen to Treg cells in vivo remain
      largely undefined. By tracking a clonal population of Aire-dependent, prostate
      specific Treg cells in mice, we demonstrated an essential role for dendritic
      cells (DCs) in regulating organ-specific Treg cell biology. We have shown that
      the thymic development of prostate-specific Treg cells required antigen
      presentation by DCs. Moreover, Batf3-dependent CD8alpha(+) DCs were dispensable
      for the development of this clonotype and had negligible impact on the polyclonal
      Treg cell repertoire. In the periphery, CCR7-dependent migratory DCs coordinated
      the activation of organ-specific Treg cells in the prostate-draining lymph nodes.
      Our results demonstrate that the development and peripheral regulation of organ
      specific Treg cells are dependent on antigen presentation by DCs, implicating DCs
      as key mediators of organ-specific immune tolerance.

PMID- 27037191
TI  - Human Monocytes Engage an Alternative Inflammasome Pathway.
AB  - Interleukin-1beta (IL-1beta) is a cytokine whose bioactivity is controlled by
      activation of the inflammasome. However, in response to lipopolysaccharide, human
      monocytes secrete IL-1beta independently of classical inflammasome stimuli. Here,
      we report that this constituted a species-specific response that is not observed
      in the murine system. Indeed, in human monocytes, lipopolysaccharide triggered an
      "alternative inflammasome" that relied on NLRP3-ASC-caspase-1 signaling, yet was
      devoid of any classical inflammasome characteristics including pyroptosome
      formation, pyroptosis induction, and K(+) efflux dependency. Genetic dissection
      of the underlying signaling pathway in a monocyte transdifferentiation system
      revealed that alternative inflammasome activation was propagated by TLR4-TRIF
      RIPK1-FADD-CASP8 signaling upstream of NLRP3. Importantly, involvement of this
      signaling cascade was limited to alternative inflammasome activation and did not
      extend to classical NLRP3 activation. Because alternative inflammasome activation
      embraces both sensitivity and promiscuity of TLR4, we propose a pivotal role for
      this signaling cascade in TLR4-driven, IL-1beta-mediated immune responses and
      immunopathology in humans.

PMID- 27037190
TI  - Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates
      Inflammation In Vivo.
AB  - Few apoptotic corpses are seen even in tissues with high cellular turnover,
      leading to the notion that the capacity for engulfment in vivo is vast. Whether
      corpse clearance can be enhanced in vivo for potential benefit is not known. In a
      colonic inflammation model, we noted that the expression of the phagocytic
      receptor Bai1 was progressively downmodulated. Consistent with this, BAI1
      deficient mice had more pronounced colitis and lower survival, with many
      uncleared apoptotic corpses and inflammatory cytokines within the colonic
      epithelium. When we engineered and tested transgenic mice overexpressing BAI1,
      these had fewer apoptotic cells, reduced inflammation, and attenuated disease.
      Boosting BAI1-mediated uptake by intestinal epithelial cells (rather than myeloid
      cells) was important in attenuating inflammation. A signaling-deficient BAI1
      transgene could not provide a similar benefit. Collectively, these complementary
      genetic approaches showed that cell clearance could be boosted in vivo, with
      potential to regulate tissue inflammation in specific contexts.

PMID- 27037192
TI  - Low-Voltage-Activated CaV3.1 Calcium Channels Shape T Helper Cell Cytokine
      Profiles.
AB  - Activation of T cells is mediated by the engagement of T cell receptors (TCRs)
      followed by calcium entry via store-operated calcium channels. Here we have shown
      an additional route for calcium entry into T cells-through the low-voltage
      activated T-type CaV3.1 calcium channel. CaV3.1 mediated a substantial current at
      resting membrane potentials, and its deficiency had no effect on TCR-initiated
      calcium entry. Mice deficient for CaV3.1 were resistant to the induction of
      experimental autoimmune encephalomyelitis and had reduced productions of the
      granulocyte-macrophage colony-stimulating factor (GM-CSF) by central nervous
      system (CNS)-infiltrating T helper 1 (Th1) and Th17 cells. CaV3.1 deficiency led
      to decreased secretion of GM-CSF from in vitro polarized Th1 and Th17 cells.
      Nuclear translocation of the nuclear factor of activated T cell (NFAT) was also
      reduced in CaV3.1-deficient T cells. These data provide evidence for T-type
      channels in immune cells and their potential role in shaping the autoimmune
      response.

PMID- 27037193
TI  - Olfactory and erectile dysfunction association in smoking and non-smoking men.
AB  - The studies evaluating the effect of smoking on olfaction reveals opposite
      results. In vitro and animal studies and epidemiological evidence from volunteers
      and patients, demonstrated the association between olfaction and erectile
      functions. In smoking man the reduction of olfactory acuity could adversely
      affect sexuality. The aim of the present study was to investigate the
      relationship between erectile dysfunction (ED) and olfactory dysfunction (OD) by
      comparing a group of healthy adult men with a group of smoking adult men. This
      prospective study involved 62 volunteers, who were recruited and divided into two
      groups; one consisted of 35 smoking adult men, and the other included 27 healthy
      non-smoking men. All participants in both groups were examined in detail for any
      condition with the potential to cause OD. They all had a normal genitourinary
      system suffered from no circulatory diseases, diabetes mellitus, hypertension,
      coronary artery disease nor hyperlipidemia; they had no history of medication
      affecting genitourinary system. Butanol threshold test and sniffin' stick(r)
      (Burghart, Wedel; Germany) screening test was used to asses olfactory functions
      in both groups. Participants' sexual desire was assessed using an International
      Index of Erectile Function (IIEF-5) scale. The means of sniffin' sticks scores,
      butanol threshold scores and IIEF-5 scores were statistically higher in non
      smoking group. Butanol threshold scores and sniffin' sticks scores are correlated
      statistically with IIEF-5 in non-smoking and smoking groups. This study found an
      association between olfaction and erectile function in smoking and non-smoking
      men. As far as we know this study is the third published study to show the
      relationship olfactory and erectile function. In the future studies
      electrophysiological olfactory methods could be used to confirm in large cohorts
      the results obtained by the psychophysical approach.

PMID- 27037194
TI  - Ozone Inhalation Provokes Glucocorticoid-Dependent and -Independent Effects on
      Inflammatory and Metabolic Pathways.
AB  - Growing evidence implicates air pollutants in adverse health effects beyond
      respiratory and cardiovascular disease, including metabolic impacts (diabetes,
      metabolic syndrome, obesity) and neurological/neurobehavioral outcomes
      (neurodegenerative disease, cognitive decline, perceived stress, depression,
      suicide). We have shown that inhalation of particulate matter or ozone activates
      the hypothalamic-pituitary-adrenal axis in rats and increases plasma levels of
      the glucocorticoid corticosterone. To investigate the role of corticosterone in
      mediating inflammatory and metabolic effects of pollutant exposure, in this study
      male Fischer-344 rats were administered the 11beta-hydroxylase inhibitor
      metyrapone (0, 50, 150 mg/kg body weight) and exposed by nose-only inhalation for
      4 h to air or 0.8 ppm ozone. Ozone inhalation provoked a 2-fold increase in
      plasma corticosterone, an effect blocked by metyrapone, but did not alter
      epinephrine levels. Inhibition of corticosterone production was associated with
      increased inflammatory signaling in the lungs and plasma in response to ozone,
      consistent with a role for glucocorticoids in limiting local and systemic
      inflammatory responses. Effects of ozone on insulin and glucagon, but not ghrelin
      or plasminogen activator inhibitor-1, were modified by metyrapone, revealing
      glucocorticoid-dependent and -independent effects on circulating metabolic and
      hemostatic factors. Several immunosuppressive and metabolic impacts of ozone in
      the lungs, heart, liver, kidney, and spleen were blocked by metyrapone and
      reproduced through exogenous administration of corticosterone (10 mg/kg body
      weight), demonstrating glucocorticoid-dependent effects in target tissues. Our
      results support involvement of endogenous glucocorticoids in ozone-induced
      inflammatory and metabolic effects, providing insight into potential biological
      mechanisms underlying health impacts and susceptibility.

PMID- 27037195
TI  - Editorial Overview: Molecular Mechanisms of Autophagy-Part A.

PMID- 27037196
TI  - Hackers demand ransom to release encrypted US medical records.

PMID- 27037197
TI  - Tumor necrosis factor drives increased splenic monopoiesis in old mice.
AB  - Aging is accompanied by changes in hematopoiesis and consequently in leukocyte
      phenotype and function. Although age-related changes in bone marrow hematopoiesis
      are fairly well documented, changes in extramedullary hematopoiesis are less well
      described. We observed that 18-22-mo-old mice had larger spleens than young
      controls and found that the enlargement was caused by increased monopoiesis.
      Because extramedullary hematopoiesis is often driven by inflammation, we
      hypothesized that the chronic, low-level inflammation that occurs with age is a
      causal agent in splenomegaly. To test this theory, we compared the number of
      monocytes in 18-mo-old tumor necrosis factor-knockout mice, which are protected
      from age-associated inflammation, and found that they did not have increased
      extramedullary monopoiesis. To determine whether increased splenic monopoiesis is
      caused by intrinsic changes in the myeloid precursors that occur with age or by
      the aging microenvironment, we created heterochronic bone marrow chimeras.
      Increased splenic monopoiesis occurred in old recipient mice, regardless of the
      age of the donor mouse, but not in young recipient mice, demonstrating that these
      cells respond to signals from the microenvironment. These data suggest that
      decreasing the inflammatory microenvironment with age would be an effective
      strategy for reducing inflammatory diseases propagated by cells of myeloid
      lineage, which increase in number with age.

PMID- 27037198
TI  - A systematic review of the role of periadventitial dissection of the superior
      mesenteric artery in affecting margin status after pancreatoduodenectomy for
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Resectable pancreatic ductal adenocarcinoma continues to carry a poor
      prognosis. Of the controllable clinical variables known to affect outcome, margin
      status is paramount. Though the importance of a R0 resection is generally
      accepted, not all margins are easily managed. The superior mesenteric artery
      [SMA] in particular is the most challenging to clear. The aim of this study was
      to systematically review the literature with specific focus on the role of a SMA
      periadventitial dissection during PD and it's effect on margin status in
      pancreatic adenocarcinoma. STUDY DESIGN: The MEDLINE, EMBASE and Cochrane
      databases were searched for abstracts that addressed the effect of margin status
      on survival and recurrence following pancreaticoduodenectomy [PD]. Quantitative
      analysis was performed. RESULTS: The overall incidence of a R1 resection ranged
      from 16% to 79%. The margin that was most often positive following PD was the SMA
      margin, which was positive in 15-45% of resected specimens. Most studies
      suggested that a positive margin was associated with decreased survival. No
      consistent definition of R0 resection was observed. CONCLUSIONS: Margin
      positivity in resectable pancreatic adenocarcinoma is associated with poor
      survival. Inability to clear the SMA margin is the most common cause of
      incomplete resection. More complete and consistently reported data are needed to
      evaluate the potential effect of periadventitial SMA dissection on margin status,
      local recurrence, or survival.

PMID- 27037199
TI  - Systematic review and meta-analysis of outcomes after liver resection in patients
      with hepatocellular carcinoma (HCC) with and without bile duct thrombus.
AB  - INTRODUCTION: This meta-analysis aimed to compare perioperative and survival
      outcomes in patients who underwent hepatectomy with and without Bile Duct Tumour
      Thrombus (BDTT). METHODS: A comprehensive search of Cochrane Library, PubMed,
      MEDLINE and EMBASE was performed to identify relevant articles. The
      perioperative, postoperative and long term outcomes were compared. RESULTS:
      Eleven studies including 6051 patients met the inclusion criteria. The
      perioperative outcomes were comparable between the 2 groups. The BDTT group had
      higher proportion poorly differentiated tumours (OR = 1.87, X(2) = 10.00, df = 6,
      p = 0.002, I(2) = 40%), Lymphovascular invasion (LVI) (OR = 4.85, X(2) = 28.21,
      df = 9, p = <0.001, I(2) = 68%) and Macrovascular invasion (MVI) (OR = 5.41, X(2)
      = 8.73, df = 9, p = <0.001, I(2) = 0%). There was no difference in 1 and 3 year
      survival, however 5-yr survival was poorer in the BDTT group (OR = 0.37, X(2) =
      37.04, df = 7, p = <0.001, I(2) = 81%). The mean difference (MD) in overall
      survival in the BDTT group was -20 months [-32.31, -7.06], p = 0.002, I(2) = 95%.
      CONCLUSION: Patients with HCC with BDTT had more advanced stage HCC with adverse
      histological features including higher rates of MVI, LVI and poor
      differentiation. Hepatectomy in this group of patients offers similar survival at
      3 years but inferior long-term survival and should be considered when feasible.

PMID- 27037200
TI  - Volume-outcome relationships in pancreatoduodenectomy for cancer.
AB  - BACKGROUND: Volume-outcome relationships in pancreatic surgery are well
      established, but an optimal volume remains to be determined. Studies analyzing
      outcomes in volume categories exceeding 20 procedures annually are lacking. STUDY
      DESIGN: A consecutive 3420 patients underwent PD for primary pancreatic or
      periampullary carcinoma (2005-2013) and were registered in the Netherlands Cancer
      Registry. Relationships between hospital volume (< 5, 5-19, 20-39 and >= 40
      PDs/year) and mortality and survival were explored. RESULTS: There was a non
      significant decrease in 90-day mortality from 8.1 to 6.7% during the study period
      (p = 0.23). Ninety-day mortality was 9.7% in centers performing < 5 PDs/year (n =
      185 patients), 8.9% for 5-19 PDs/year (n = 1432), 7.3% for 20-39 PDs/year (n =
      240) and 4.3% for >= 40 PDs/year (n = 562, p = 0.004). Within volume categories,
      90-day mortality did not change over time. After adjustment for confounding
      factors, significantly lower mortality was found in the >= 40 category compared
      to 20-39 PDs/year (OR = 1.72 (1.08-2.74)). Overall survival adjusted for
      confounding factors was better in the >= 40 category compared to categories under
      20 PDs/year: HR (>= 40 vs 5-19/year) = 1.24 (1.09-1.42). In the >= 40 category
      significantly more patients received adjuvant chemotherapy and had > 10 lymph
      nodes retrieved compared to lower volume categories. CONCLUSIONS: Volume-outcome
      relationships in pancreatic surgery persist in centers performing >= 40 PDs
      annually, regarding both mortality and survival. The volume plateau for
      pancreatic surgery has yet to be determined.

PMID- 27037201
TI  - Improved survival after palliative resection of unsuspected stage IV pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND: Palliative resection of stage IV pancreatic ductal adenocarcinoma
      (PDAC) has not shown its benefit until now. In our retrospective review, we
      compared the results of palliative resection to non-resection. METHODS: Between
      2000 and 2009, metastasis of PDAC was confirmed in the operating room in 150
      patients. 35 underwent palliative resection (resection group; R) and 115 did
      bypass or biopsy. 35 patients (biopsy or bypass group: NR) in the 115 patients
      were matched with the patients undergoing resection for tumor size and the
      metastasis of peritoneal seeding. Demographic, clinical, operative data and
      survival were analyzed. RESULTS: There was no significant difference of major
      complication (Clavien-Dindo classification 3-5) between two groups. There was no
      30-day mortality in either group. More patients in R received postoperative
      chemotherapy (82.9% vs. 57.1%; P = 0.019). Multivariate analysis showed resection
      and postoperative chemotherapy as independent factor related to survival (hazard
      ratio, 0.44; 95% CI, 0.25-0.76; P = 0.003). Patients in R showed better survival
      rates compared to those in NR (P < 0.001). CONCLUSION: Our study suggests
      resection for stage IV PDAC can be associated with increased survival. In
      patients of stage IV PDAC, palliative resection with chemotherapy could have some
      benefit in selected patients.

PMID- 27037202
TI  - A model to predict survival following pancreaticoduodenectomy for malignancy
      based on tumour site, stage and lymph node ratio.
AB  - BACKGROUND: Site of tumour origin, lymph node metastases and lymph node ratio
      (LNR) are identified as important factors determining prognosis in patients
      undergoing pancreaticoduodenectomy (PD). This study hypothesised that a
      prognostic index to predict survival could be developed through statistical
      modelling based on these pathological variables. METHODS: Patients who underwent
      PD between 2004 and 2013 were included. Univariable and multivariable (Cox
      regression) analyses were performed to identify predictors of survival, and a
      prognostic index was derived. The prognostic index was then validated using an
      external patient cohort. RESULTS: A total of 567 patients who underwent PD were
      used as a derivation cohort. Tumour site (p < 0.001), tumour size (p = 0.002), T
      stage (p < 0.001), vascular involvement (p = 0.002), number of positive nodes (p
      < 0.001) and LNR (p < 0.001) were significantly associated with survival in
      univariable analysis. LNR (p < 0.001), tumour site (p < 0.001), T-stage (p =
      0.007) remained significant predictors of survival in multivariable analysis, and
      were combined to derive a prognostic index. The accuracy of the prognostic index
      was assessed both on the original cohort, and a validation set of 194 patients
      from another institutional prospective database. The AUROC scores for predicting
      the overall survival at 3 years were 0.77 in the derivation cohort and 0.74 in
      the validation cohort. CONCLUSION: The Pancreaticoduodenectomy Prognostic Index
      is a validated clinico-pathological model based on tumour site, T-stage and LNR
      to predict long-term survival following PD.

PMID- 27037203
TI  - The association of adjuvant therapy with survival at the population level
      following pancreatic adenocarcinoma resection.
AB  - BACKGROUND: Using a retrospective observational cohort approach, the overall
      survival (OS) following curative-intent resection of pancreatic adenocarcinoma
      (PC) was defined at the population level according to adjuvant treatment, and
      predictors of OS were identified. METHODS: Patients undergoing resection of PC in
      the province of Ontario between 2005 and 2010 were identified using the
      provincial cancer registry, and linked to databases that include all treatments
      received and outcomes experienced in the province. Pathology reports were
      abstracted for staging and margin status. Patients were identified as having
      received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant
      treatment (NAT). Kaplan-Meier survival analysis of patients surviving >= 6 months
      was performed, and predictors of OS identified by log-rank test. Cox
      multivariable analysis was used to define independent predictors of OS. RESULTS:
      Among the 473 patients undergoing PC resection, the median survival was 17.8
      months; for the 397 who survived >= 6 months following surgery, the 5-year OS for
      the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584).
      Lymph node-negative patients demonstrated improved OS associated with
      chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25-3.83 for NAT vs.
      CT). CONCLUSIONS: Following PC resection, only patients with negative lymph nodes
      demonstrated improved OS associated with adjuvant chemotherapy.

PMID- 27037204
TI  - External biliary drainage following major liver resection for perihilar
      cholangiocarcinoma: impact on development of liver failure and biliary leakage.
AB  - BACKGROUND: Preoperative biliary drainage is considered essential in perihilar
      cholangiocarcinoma (PHC) requiring major hepatectomy with biliary-enteric
      reconstruction. However, evidence for postoperative biliary drainage as to
      protect the anastomosis is currently lacking. This study investigated the impact
      of postoperative external biliary drainage on the development of post-hepatectomy
      biliary leakage and liver failure (PHLF). METHODS: All patients who underwent
      major liver resection for suspected PHC between 2000 and 2015 were
      retrospectively analyzed. Biliary leakage and PHLF was defined as grade B or
      higher according to the International Study Group of Liver Surgery (ISGLS)
      criteria. RESULTS: Eighty-nine out of 125 (71%) patients had postoperative
      external biliary drainage. PHLF was more prevalent in the drain group (29% versus
      6%; P = 0.004). There was no difference in the incidence of biliary leakage (32%
      versus 36%). On multivariable analysis, postoperative external biliary drainage
      was identified as an independent risk factor for PHLF (Odds-ratio 10.3, 95%
      confidence interval 2.1-50.4; P = 0.004). CONCLUSIONS: External biliary drainage
      following major hepatectomy for PHC was associated with an increased incidence of
      PHLF. It is therefore not recommended to routinely use postoperative external
      biliary drainage, especially as there is no evidence that this decreases the risk
      of biliary anastomotic leakage.

PMID- 27037205
TI  - Assessment of the effect of interval from presentation to surgery on outcome in
      patients with peri-ampullary malignancy.
AB  - BACKGROUND: Delay between diagnosis of peri-ampullary cancer (PC) and surgery may
      allow tumour progression and affect outcome. The aim of this study was to explore
      associations of interval to surgery (IS) with pathological outcomes and survival
      in patients with PC. METHOD: A database review of all patients undergoing surgery
      between 2006 and 2014 was undertaken. IS was measured from diagnosis by imaging.
      Potential association between IS and survival was measured using Cox regression
      analysis, and between IS and pathological outcome with multivariate logistic
      analysis. RESULTS: 388 patients underwent surgery. The median IS was 49 days (1
      551 days), and was not associated with any of the evaluated outcomes in patients
      with pancreatic (149) or distal bile duct (46) cancer. For patients with
      ampullary cancer (71) longer IS was associated with improved survival, with
      median survival of 27.5 months for patients waiting <= median IS (35) and 38.3
      months for patients waiting > median IS (36) for surgery (p = 0.041). A higher
      rate of margin positivity (31.4%) was also noted among patients who waited less
      than the median IS compared to those waiting longer than this interval (11.4%) (p
      = 0.032). CONCLUSION: For patients with ampullary cancer there is a paradoxical
      improvement in outcome among those with a longer IS, which may be explained by
      progression to inoperability of more aggressive lesions.

PMID- 27037206
TI  - Thirty-day outcomes underestimate endocrine and exocrine insufficiency after
      pancreatic resection.
AB  - BACKGROUND: Long-term incidence of endocrine and exocrine insufficiency after
      pancreatectomy is poorly described. We analyze the long-term risks of pancreatic
      insufficiency after pancreatectomy. METHODS: Subjects who underwent
      pancreatectomy from 2002 to 2012 were identified from a prospective database (n =
      227). Subjects who underwent total pancreatectomy or pancreatitis surgery were
      excluded. New post-operative endocrine and exocrine insufficiency was defined as
      the need for new pharmacologic intervention within 1000 days from resection.
      RESULTS: 28 (16%) of 178 subjects without pre-existing endocrine insufficiency
      developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days,
      8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214
      subjects without pre-operative exocrine insufficiency developed exocrine
      insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days,
      and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine
      insufficiency. On multivariate regression, pancreaticoduodenectomy and
      chemotherapy were associated with a greater risk of exocrine insufficiency.
      CONCLUSION: Reporting 30-day functional outcomes for pancreatic resection is
      insufficient, as nearly 45% of subjects who develop disease do so after 90 days.
      Reporting of at least 90-day outcomes may more reliably assess risk for post
      operative endocrine and exocrine insufficiency.

PMID- 27037207
TI  - Early biliary complications following pancreaticoduodenectomy: prevalence and
      risk factors.
AB  - BACKGROUND: Early biliary complications (EBC) following pancreaticoduodenectomy
      (PD) are poorly known. This study aimed to assess incidence, predictive factors,
      and treatment of EBC including bilio-enteric stricture, transient jaundice,
      biliary leak, and cholangitis. METHOD: From 2007 to 2011, 352 patients underwent
      PD. Statistical analysis including logistic regression was performed to determine
      EBC predictive factors. RESULTS: 49 patients (14%) developed 51 EBC, including
      7(2%) bilio-enteric strictures, 15(4%) transient jaundices, 9(3%) biliary leaks,
      and 20(6%) cholangitis with no mortality and a 18% reoperation rate. In
      multivariate analysis, male gender, benign disease, malignancy with preoperative
      chemoradiation, and common bile duct (CBD) diameter <= 5 mm were predictive of
      EBC. Of the 7 strictures, all were associated with CBD <= 5 mm and 5(71%)
      required reoperation. Transient jaundice resolved spontaneously in all 15 cases.
      Among 8 patients with serum bilirubin level > 50 MUmol/L (3 mg/dL) at POD3,
      7(88%) developed bilio-enteric stricture. Biliary leak resolved spontaneously in
      5(56%); otherwise, it required reoperation. Cholangitis recurred after
      antibiotics discontinuation in 5(25%). CONCLUSIONS: EBC following PD do not
      increase mortality. EBC are more frequent with male gender, benign disease,
      malignancy with preoperative chemoradiation, and CBD <= 5 mm. Transient jaundice
      or cholangitis has a favorable outcome, whereas bilio-enteric stricture or
      biliary leak can require reintervention.

PMID- 27037208
TI  - National trends in resection of cystic lesions of the pancreas.
AB  - BACKGROUND: Management of cystic lesions of the pancreas (CLP) is controversial.
      In this study, we sought to evaluate national changes in the resection of CLP
      over time, to better understand the impact of evolving guidelines on CLP
      management. METHODS: We used Medicare data to examine CLP resection among
      patients undergoing pancreatic resection between 2001 and 2012. Patients with a
      diagnosis of CLP were identified and compared to patients with non-CLP
      indications. We then examined changes over time in patient and hospital
      characteristics and outcomes among patients with a CLP diagnosis. RESULTS: We
      identified 56,419 Medicare patients undergoing pancreatic resection, of which
      2129 had a CLP diagnosis. The annual number of CLP resections, and proportion of
      all resections performed for CLP increased significantly during the period, from
      2.1% (65/3072) resections in 2001, to 4.5% (286/6348) in 2012 (p < 0.001). The
      proportion of CLP resections with a malignant diagnosis did not change (15.5% in
      2001-2003 vs. 13.1% in 2010-2012, p = 0.4). Overall rates of 30-day mortality
      decreased significantly during the period (9.6% in 2001-2003 vs. 5.5% in 2010
      2012, p < 0.001). DISCUSSION: CLP resections were performed with increasing
      frequency in Medicare patients between 2001 and 2012, but this did not correspond
      to increased diagnosis of malignancy. Additional research is needed to understand
      the influence of recent guidelines on management of CLP.

PMID- 27037209
TI  - Determining the natural history of pancreatic cystic neoplasms: a Manitoban
      cohort study.
AB  - BACKGROUND: Most pancreatic cystic neoplasms (PCN) are thought to harbor a low
      malignant potential. This historical cohort study attempts to describe the
      natural history of these lesions in a provincial cohort, to assess the safety of
      non-surgical management. Pathological diagnosis of malignancy was the primary
      outcome measure of interest. METHODS: All adult patients (age 18+) with PCN seen
      between 2000 and 2012 by the two main institutions in Manitoba were included in
      this study. PCN were graded as high and low risk, which dictated initial
      treatment plan (surgery or observation). Predictors of initial surgical
      treatment, delayed surgery in the observation group and the clinical/radiological
      predictors of malignancy were determined. RESULTS: 497 patients were included in
      this study. 43 (8.7%) high-risk lesions underwent initial surgery, with 13
      (30.2%) cases of malignancy discovered. 450 (90.5%) low-risk cysts were observed
      for a median of 17.3 months (range: 0.00-142.3). 29 (6.4%) cases of delayed
      surgery occurred, with malignancy discovered in five (17.2%). CONCLUSIONS: This
      study supports current selection criteria for management of PCNs. Due to the low
      incidence of malignancy in low-risk PCN, it appears that long-term observation is
      safe and should be the treatment modality of choice in the absence of high-risk
      features.

PMID- 27037210
TI  - The influence of steatosis on the short- and long-term results of resection of
      liver metastases from colorectal carcinoma.
AB  - We aimed to establish whether the presence of hepatic steatosis influences
      outcome after resection of colorectal liver metastases (CLM). PATIENTS AND
      METHODS: Patients operated between 1990 and 2014 were divided into four groups
      based on the degree of hepatic steatosis. The association between hepatic
      steatosis and outcome was analyzed, using a multivariate and a propensity score
      case-match analysis. RESULTS: No significant differences were observed between
      patients with and without steatosis in either mortality or morbidity in the
      complete series or after matching (3.2% vs. 3.5%/p = 0.845) (32.3% vs 31.4%/p =
      0.802). Five-year survival in patients with and without steatosis were 56.5% and
      46.5% respectively (p = 0.046). The steatosis had a significant protective effect
      in the univariate analysis (HR (95% CI) = 0.78 (0.62-0.99) p = 0.048), and was
      close to significance in the multivariate analysis (HR (95%) = 0.81 (0.63-1.03) p
      = 0.089). No significant differences were seen with regard to liver recurrence.
      CONCLUSIONS: The presence of steatosis does not predict short-outcome after
      resection of CLM, but appears to be a favorable prognostic factor for survival.
      This protective effect does not depend on a decrease in liver recurrence.

PMID- 27037212
TI  - Boost for Alginate Encapsulation in Beta Cell Transplantation.
AB  - A recent study reported that encapsulation of human embryonic stem cell (hESC)
      derived beta cells by a novel alginate formula protects against foreign body
      reactivity in immune-competent mice. Intraperitoneal implants corrected a
      diabetic state for at least 6 months. These observations will stimulate the
      development of alginate encapsulation towards novel cell therapy protocols for
      treating type 1 diabetes (T1DM).

PMID- 27037211
TI  - Genomic Aberrations Drive Clonal Evolution of Neuroendocrine Tumors.
AB  - Molecular features of castration-resistant neuroendocrine prostate cancer (CRPC
      NE) are not well characterized. A recent study that investigated genomic
      aberrations of CRPC-NE tumors suggests their clonal evolution from CRPC
      adenocarcinoma. Furthermore, the existence of a distinct DNA methylation profile
      in CRPC-NE implicates a critical role for epigenetic modification in the
      development of CRPC-NE.

PMID- 27037213
TI  - Editorial independence: painful lessons.

PMID- 27037214
TI  - Multiple enchondromas and skin angiomas: Maffucci syndrome.

PMID- 27037215
TI  - Associations of olfactory bulb and depth of olfactory sulcus with basal ganglia
      and hippocampus in patients with Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      hyposmia in the preclinical stages. We investigated the relationships of
      olfactory bulb (OB) volume and olfactory sulcus (OS) depth with basal ganglia and
      hippocampal volumes. The study included 25 patients with PD and 40 age- and sex
      matched control subjects. Idiopathic PD was diagnosed according to published
      diagnostic criteria. The Hoehn and Yahr (HY) scale, the motor subscale of the
      Unified Parkinson's Disease Rating Scale (UPDRS III), and the Mini-Mental State
      Examination (MMSE) were administered to participants. Volumetric measurements of
      olfactory structures, the basal ganglia, and hippocampus were performed using
      magnetic resonance imaging (MRI). OB volume and OS depth were significantly
      reduced in PD patients compared to healthy control subjects (p<0.001 and p<0.001,
      respectively). The OB and left putamen volumes were significantly correlated
      (p=0.048), and the depth of the right OS was significantly correlated with right
      hippocampal volume (p=0.018). We found significant correlations between OB and
      putamen volumes and OS depth and hippocampal volume. Our study is the first to
      demonstrate associations of olfactory structures with the putamen and hippocampus
      using MRI volumetric measurements.

PMID- 27037216
TI  - Effects of rapamycin pretreatment on blood-brain barrier disruption in cerebral
      ischemia-reperfusion.
AB  - The mammalian target of rapamycin (mTOR) pathway is essential in neuronal
      survival and repair in cerebral ischemia. Decreases in blood-brain barrier (BBB)
      disruption are associated with a decrease in neuronal damage in cerebral
      ischemia. This study was performed to investigate how pre-inhibition of the mTOR
      pathway with rapamycin would affect BBB disruption and the size of the infarcted
      cortical area in the early stage of focal cerebral ischemia-reperfusion using
      quantitative analysis of BBB disruption. Rats were treated with 20mg/kg of
      rapamycin i.p. once a day for 2days (Rapamycin Group) or vehicle (Control Group)
      before transient middle cerebral artery (MCA) occlusion. After one hour of MCA
      occlusion and two hours of reperfusion, the transfer coefficient (Ki) of (14)C
      alpha-aminoisobutyric acid ((14)C-AIB) to measure the degree of BBB disruption
      and the size of the cortical infarct were determined. Ischemia-reperfusion
      increased the Ki in the Rapamycin treated (+15%) as well as in the untreated
      control group (+13%). However, rapamycin pretreatment moderately decreased Ki in
      the contralateral (-30%) as well as in the ischemic-reperfused (-29%) cortex when
      compared with the untreated control group. Rapamycin pretreatment substantially
      increased the percentage of cortical infarct compared with the control group
      (+56%). Our data suggest that activation of mTOR pathway is necessary for
      neuronal survival in the early stage of cerebral ischemia-perfusion and that the
      reason for the enlarged cortical infarct by rapamycin pretreatment may be related
      to its non-BBB effects on the mTOR pathway.

PMID- 27037217
TI  - Efficacy and Safety of Transbrachial Access for Iliac Endovascular Interventions.
AB  - PURPOSE: To evaluate the use of a brachial artery access for endovascular
      treatment of iliac artery disease. METHODS: A retrospective review was conducted
      of 201 patients (mean age 73 years; 147 men) treated via a brachial artery access
      for iliac artery stenosis. The majority (n=141, 70%) presented with lifestyle
      limiting claudication (Rutherford category 3), whereas the incidence of critical
      limb ischemia (Rutherford categories 4-6) was 30% (n=70). Diagnostic angiography
      revealed a TransAtlantic Inter-Society Consensus II (TASC) C/D lesion in 114
      (57%) patients. The primary outcome was technical success achieved exclusively
      with a brachial artery access. Secondary outcomes were secondary technical
      success (adjunctive transfemoral access), access site complications, and
      stroke/transient ischemic attack (TIA). RESULTS: In 17 (8%) patients, lesion
      crossing was unsuccessful, while an adjunctive transfemoral approach was
      necessary to restore iliac vessel patency in 23 (11%) cases. Thus, the primary
      and secondary technical success rates were 81% and 92%, respectively. Local
      hematomas (9, 4%) dominated the access site complications, followed by
      pseudoaneurysms (8, 4%), late brachial artery bleeding (4, 2%), brachial artery
      occlusion (2, 1%), and puncture site infection (2, 1%). No transient or permanent
      median nerve dysfunction was observed. The stroke/TIA rate was 2% (n=4). A single
      patient died due to acute coronary syndrome (0.5% mortality). TASC II class
      (p=0.58), sex (p=0.66), and target vessel (p>0.3 for all locations) had no effect
      on technical success. Female gender unfavorably influenced the incidence of
      access site complications (hazard ratio 6.7, 95% confidence interval 2.7 to 15,
      p<0.001), but sheath size did not (p=0.22). CONCLUSION: Brachial artery access
      enables endovascular treatment of iliac artery disease in the majority of
      patients, although an adjunctive transfemoral access may be required. However,
      the high incidences of access site complications and cerebral events remain a
      significant limitation of the transbrachial approach.

PMID- 27037218
TI  - Transcriptomics provides insight into Mytilus galloprovincialis (Mollusca:
      Bivalvia) mantle function and its role in biomineralisation.
AB  - The mantle is an organ common to all molluscs and is at the forefront of the
      biomineralisation process. The present study used the Mediterranean mussel
      (Mytilus galloprovincialis) as a model species to investigate the structural and
      functional role of the mantle in shell formation. The transcriptomes of three
      regions of the mantle edge (umbo to posterior edge) were sequenced using Illumina
      technology which yielded a total of 61,674,325 reads after adapter trimming and
      filtering. The raw reads assembled into 179,879 transcripts with an N50 value of
      1086bp. A total of 1363 transcripts (321, 223 and 816 in regions 1, 2 and 3,
      respectively) that differed in abundance in the three mantle regions were
      identified and putative function was assigned to 54% using BLAST sequence
      similarity searches (cut-off less than 1e(-10)). Morphological differences
      detected by histology of the three mantle regions was linked to functional
      heterogeneity by selecting the top five most abundant Pfam domains in the
      annotated 1363 differentially abundant transcripts across the three mantle
      regions. Calcium binding domains dominated region two (middle segment of the
      mantle edge). Candidate biomineralisation genes were mined and tested by qPCR.
      This revealed that Flp-like, a penicillin binding protein potentially involved in
      shell matrix maintenance of the Pacific oyster (Crassostrea gigas), had
      significantly higher expression in the posterior end of the mantle edge (region
      one). Our findings are intriguing as they indicate that the mantle edge appears
      to be a heterogeneous tissue, displaying structural and functional bias. 

PMID- 27037219
TI  - Identification and characterization of three TLR1 subfamily members from the
      orange-spotted grouper, Epinephelus coioides.
AB  - Toll-like receptors (TLRs), which play important roles in host defense against
      pathogen infection, are the most intensively studied pattern recognition
      receptors (PRRs). In this study, we identified three novel TLR1 subfamily
      members, including TLR1 (EcTLR1b), TLR2 (EcTLR2b) and TLR14 (EcTLR14), from the
      orange-spotted grouper (Epinephelus coioides). EcTLR1b and EcTLR2b displayed low
      sequence identity with the previously reported grouper TLR1 (EcTLR1a) and TLR2
      (EcTLR2a), respectively. The open reading frames (ORFs) of EcTLR1b, EcTLR2b and
      EcTLR14 contain 2484 bp, 2394 bp and 2640 bp, which encode the corresponding 827
      amino acids (aa), 797 aa and 879 aa, respectively. All three TLRs have leucine
      rich repeat (LRR) domains (including an LRR-NT (except for EcTLR1b), several LRR
      motifs and an LRR-CT), a trans-membrane region and a Toll/interleukin-1 receptor
      (TIR) domain. The TIR domains of the three TLRs exhibited conserved boxes, namely
      box1, box2 and box3, and their 3D models were similar to those of human TLR1 or
      TLR2. Sequence alignment demonstrated that the TIR domains of the three TLRs
      shared higher sequence identity with those of other species than the full-length
      receptors. Phylogenetic analysis indicated that EcTLR1s and EcTLR2s are
      characterized by their differing evolutionary status, whereas EcTLR14 was found
      to be in the same group as other piscine TLR14/18s. The three TLRs were
      ubiquitously expressed in seven tested tissues of healthy groupers, although
      their expression profiles were different. Post Cryptocaryon irritans infection,
      TLR1s expression was up-regulated in the gills. The expression of TLR2b was
      mainly increased in the spleen, but decreased in the gills, which was similar to
      the expression pattern of TLR2a post C. irritans infection. Unlike EcTLR1b and
      EcTLR2b, however, the grouper TLR14 transcript was substantially induced in both
      tissues post challenge. These findings may be helpful in understanding the innate
      immune mechanism of host anti-parasite infection.

PMID- 27037220
TI  - Collecting data on violence against children and young people: need for a
      universal standard.
AB  - Preventing and responding to violence against children is an aim of the new
      Sustainable Development Goals. Numerous agencies are now collecting data from
      children about violence, including academics, non-governmental organisations,
      government agencies, consultants and others. Data are necessary to ensure
      appropriate prevention and response, but there is a real risk of harm to children
      if ethical standards are not adhered to. There are additional complexities in
      settings where child protection systems are not well developed. We propose
      specific suggestions for good practice, based on our past experience and
      policies, and call for all agencies to adhere to high ethical standards.

PMID- 27037221
TI  - Consumer preferences for food labels on tomatoes in Germany - A comparison of a
      quasi-experiment and two stated preference approaches.
AB  - In many studies, consumer preferences are determined by using direct surveys. For
      this method social desirability is problematic. This leads to the effect that
      participants answer in a way that they perceive as desired by society. This leads
      to the stated importance of certain features in these studies not being reflected
      in real purchasing decisions. Therefore, the aim of the study is to compare
      consumer preferences measured by a quasi-experiment to those quantified by direct
      questions. Another objective is to quantify the part-worth utilities of product
      characteristics such as origin, price and food labels. Part-worth utilities are
      estimated on an interval scale with an arbitrary origin and are a measure for
      preferences. The real purchasing situation was simulated in a quasi-experiment
      using a choice-based conjoint analysis. The part-worth utilities were then
      compared with the results of a conventional preference assessment (Likert scale).
      For this purpose, 645 consumers from all over Germany were surveyed in 2014. The
      participants were on average 44 years old and 63% were women. The results of the
      conjoint analysis report the highest part-worth utility (2.853) for the lowest
      price (1.49?), followed by the characteristic "grown locally" (2.157). For the
      labels, the German organic label shows the highest part-worth utility (0.785)
      followed by Fairtrade/"A heart for the producer" (0.200). It is noticeable that
      the carbon footprint labels have negative part-worth utilities compared to
      tomatoes without a label (-0.130 with CO2 indication, -0.186 without CO2
      indication). The price is ranked 12th in the importance of the characteristics of
      purchasing tomatoes in the survey with a Likert scale, whereas it is first in the
      evaluation of the quasi-experiment (conjoint analysis), which supports the
      assumption of a social desirability bias.

PMID- 27037222
TI  - Elasticity in portion selection is predicted by severity of anorexia and food
      type in adolescents.
AB  - The size of portions that people select is an indicator of underlying mechanisms
      controlling food intake. Fears of eating excessive portions drive down the sizes
      of portions patients with anorexia nervosa (AN) can tolerate eating significantly
      below those of healthy controls (HC) (Kissileff et al., 2016). To determine
      whether patients with AN will also reduce the sizes of typical or ideal portions
      below those of controls, ANOVA was used to compare maximum tolerable, typical,
      and ideal portions of four foods (potatoes, rice, pizza, and M&M's) in the same
      group of 24 adolescent AN patients and 10 healthy adolescent controls (HC), on
      which only the maximal portion data were previously reported. Typical and ideal
      portion sizes did not differ on any food for AN, but for HC, typical portions
      sizes (kcals) became larger than ideal as the energy density of the food
      increased, and were significant for the most energy dense food. Ideal portions of
      low energy dense foods were the same for AN as for in HC. There was a significant
      3-way (group * food * portion type) interaction, such that HC selected larger
      maximum than typical portions only for pizza. We therefore proposed that
      individuals of certain groups, depending on the food, can be flexible in the
      amounts of food chosen to be eaten. We call this difference between maximum
      tolerable, and typical portion sizes selected "elasticity." Elasticity was
      significantly smaller for AN patients compared to HC for pizza and was
      significantly inversely correlated with severity of illness. This index could be
      useful for clinical assessment of AN patients, and those with eating problems
      such as in obesity and bulimia nervosa and tracking their response to treatment.

PMID- 27037224
TI  - Cancer-associated thrombosis.

PMID- 27037225
TI  - The use of systemic antibiotics in the treatment of refractory periodontitis: A
      systematic review.
AB  - BACKGROUND: The goal in treating refractory periodontitis (RP) is to arrest or
      slow disease progression, which usually has included the use of systemic
      antibiotics adjunct to conventional mechanical debridement. The aim of this
      systematic review was to evaluate the evidence that the association of systemic
      antibiotics with conventional mechanical debridement increases the efficacy of
      periodontal therapy in the treatment of RP. TYPES OF STUDIES REVIEWED: The
      authors searched for studies in PubMed MEDLINE, Cochrane Central Register of
      Controlled Trials, Thomson Reuters Web of Science, Scopus, Latin American and
      Caribbean Center on Health Sciences Information, and Scientific Electronic
      Library Online electronic databases by using selected key words from the earliest
      records up through October 31, 2014. Only clinical intervention studies in which
      investigators compared the treatment of participants with RP with either
      mechanical debridement alone or associated with systemic antibiotics were
      eligible for selection. Two authors independently assessed the risk of bias of
      each selected study. RESULTS: The authors identified 13 articles and included 6
      of them. Investigators in all studies reported greater reductions in probing
      depth or in loss of clinical attachment level after adjunct systemic antibiotic
      therapy when compared with mechanical debridement alone. Antibiotics tested
      included metronidazole, clindamycin, tetracycline hydrochloride, amoxicillin, and
      amoxicillin and potassium clavulanate. Five studies presented a high risk of
      bias, and 1 study presented an unclear risk. CONCLUSIONS AND PRACTICAL
      IMPLICATIONS: The overall quality of the evidence does not allow the conclusion
      that adjunct systemic antibiotics are of additional benefit to conventional
      mechanical debridement alone.

PMID- 27037226
TI  - Resident dashboards: helping your clinical competency committee visualize
      trainees' key performance indicators.
AB  - INTRODUCTION: Under the Next Accreditation System, programs need to find ways to
      collect and assess meaningful reportable information on its residents to assist
      the program director regarding resident milestone progression. This paper
      discusses the process that one large Internal Medicine Residency Program used to
      provide both quantitative and qualitative data to its clinical competency
      committee (CCC) through the creation of a resident dashboard. METHODS: Program
      leadership at a large university-based program developed four new end of rotation
      evaluations based on the American Board of Internal Medicine (ABIM) and
      Accreditation Council of Graduated Medical Education's (ACGME) 22 reportable
      milestones. A resident dashboard was then created to pull together both milestone
      and non-milestone-based quantitative data and qualitative data compiled from
      faculty, nurses, peers, staff, and patients. RESULTS: Dashboards were distributed
      to the members of the CCC in preparation for the semiannual CCC meeting. CCC
      members adjudicated quantitative and qualitative data to present their cohort of
      residents at the CCC meeting. Based on the committee's response, evaluation
      scores remained the same or were adjusted. Final milestone scores were then
      entered into the accreditation data system (ADS) on the ACGME website.
      CONCLUSIONS: The process of resident assessment is complex and should comprise
      both quantitative and qualitative data. The dashboard is a valuable tool for
      program leadership to use both when evaluating house staff on a semiannual basis
      at the CCC and to the resident in person.

PMID- 27037227
TI  - Quantitative MRI reveals decelerated fatty infiltration in muscles of active FSHD
      patients.
AB  - OBJECTIVE: To investigate the effects of aerobic exercise training (AET) and
      cognitive-behavioral therapy (CBT), directed towards an increase in daily
      physical activity, on the progression of fatty infiltration and edema in skeletal
      muscles of patients with facioscapulohumeral muscular dystrophy (FSHD) type 1 by
      T2 MRI. METHODS: Quantitative T2 MRI (qT2 MRI) and fat-suppressed T2 MRI of the
      thigh were performed at 3T on 31 patients, 13 of whom received usual care (UC), 9
      AET, and 9 CBT. Muscle-specific fat fractions (%), derived from qT2 MRI, were
      recorded pretreatment and posttreatment. Intervention effects were analyzed by
      comparing fat fraction progression rates of the UC with the treated groups using
      Mann-Whitney tests, and intermuscle differences by a linear mixed model.
      Edematous hyperintense lesions were identified on the fat-suppressed T2 MRI.
      RESULTS: The intraclass correlation coefficient for reproducibility of qT2 MRI
      fat assessment was 0.99. In the UC group, the fat fraction increased by 6.7/year
      (95% confidence interval [CI] 4.3 to 9.1). This rate decreased to 2.9/year (95%
      CI 0.7 to 5.2) in the AET (p = 0.03) and 1.7/year (95% CI -0.2 to 3.6) in the CBT
      group (p = 0.00015). The treatment effect differed among individual muscles.
      Fewer new edematous lesions occurred after therapy. CONCLUSIONS: Fat fraction
      derived from qT2 MRI is a reproducible and sensitive biomarker to monitor the
      effects of increased physical activity in individual muscles. This biomarker
      reports a favorable effect of AET and CBT on the rate of muscular deterioration
      in FSHD as reflected in decelerated fat replacement. CLASSIFICATION OF EVIDENCE:
      This study provides Class II evidence that for patients with FSHD type 1, both
      AET and CBT decrease the rate of fatty infiltration in muscles.

PMID- 27037228
TI  - Rituximab treatment for autoimmune limbic encephalitis in an institutional
      cohort.
AB  - OBJECTIVE: To determine efficacy and safety of rituximab treatment as a second
      line immunotherapy treatment for autoimmune limbic encephalitis (ALE) and to
      determine factors associated with functional improvement and favorable outcome
      following rituximab treatment. METHODS: We recruited 80 patients with ALE who
      were treated with rituximab as a second-line immunotherapy from the Korea
      Autoimmune Synaptic and Paraneoplastic Encephalitis Registry and reviewed 81
      patients without rituximab as a control. We grouped patients according to the
      detection or type of antibodies; in addition, we evaluated clinical, laboratory,
      first-line immunotherapy, and rituximab treatment profiles and defined main
      outcomes as improvements on the modified Rankin Scale (mRS) score and a favorable
      mRS score (0-2) at the last follow-up. RESULTS: Functional improvement occurred
      more frequently in the rituximab group compared to the control group. In the
      rituximab group, 30 (37.5%) patients had synaptic autoantibodies, 15 (18.8%) in
      the paraneoplastic autoantibodies, and 35 (43.8%) were antibody-negative. The
      effect of rituximab was the same regardless of autoantibody status. Additional
      monthly rituximab therapy and partial response to first-line immunotherapies were
      associated with mRS score improvements, as well as favorable mRS scores. mRS
      scores of 4-6 as the worst neurologic status predicted an unfavorable mRS score.
      There were no reported serious infusion-related or infectious adverse effects of
      rituximab. CONCLUSIONS: Rituximab is effective and safe as a second-line
      immunotherapy for ALE, regardless of autoantibody status. Additional monthly
      rituximab therapy might potentiate the efficacy of rituximab. CLASSIFICATION OF
      EVIDENCE: This study provides Class IV evidence that rituximab improves mRS
      scores for patients with autoimmune limbic encephalitis who fail first-line
      therapy.

PMID- 27037230
TI  - The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies.
AB  - OBJECTIVE: To assess the clinical relevance of a positive voltage-gated potassium
      channel (VGKC) test in patients lacking antibodies to LGI1 and Caspr2. METHODS:
      VGKC-positive patients were tested for LGI1 and Caspr2 antibodies. Patients
      lacking both antibodies were matched (1:2) to VGKC-negative patients. Clinical
      and paraclinical criteria were used to blindly determine evidence for autoimmune
      inflammation in both groups. Patients with an inconclusive VGKC titer were
      analyzed in the same way. RESULTS: A total of 1,455 patients were tested by VGKC
      radioimmunoassay. Fifty-six patients tested positive, 50 of whom were available
      to be included. Twenty-five patients had antibodies to LGI1 (n = 19) or Caspr2 (n
      = 6) and 25 patients lacked both antibodies. Evidence for autoimmune inflammation
      was present in 7 (28%) of the VGKC-positive patients lacking LGI1 and Caspr2,
      compared to 9 (18%) of the VGKC-negative controls (p = 0.38). Evidence for
      autoimmune inflammation was mainly found in patients with limbic
      encephalitis/encephalomyelitis (57%), but not in other clinical phenotypes (5%, p
      < 0.01). VGKC titers were significantly higher in patients with antibodies to
      LGI1 or Caspr2 (p < 0.001). However, antibodies to Caspr2 could also be detected
      in patients with inconclusive low VGKC titer, while many VGKC-positive patients
      had no evidence for autoimmune inflammation. CONCLUSIONS: VGKC positivity in the
      absence of antibodies to LGI1 and Caspr2 is not a clear marker for autoimmune
      inflammation and seems not to contribute in clinical practice. No cutoff value
      for the VGKC titer was appropriate to discriminate between patients with and
      without autoimmune inflammation.

PMID- 27037231
TI  - Rare ABCA7 variants in Alzheimer disease: Guilt by association.

PMID- 27037229
TI  - ABCA7 rare variants and Alzheimer disease risk.
AB  - OBJECTIVE: To study the association between ABCA7 rare coding variants and
      Alzheimer disease (AD) in a case-control setting. METHODS: We conducted a whole
      exome analysis among 484 French patients with early-onset AD and 590 ethnically
      matched controls. RESULTS: After collapsing rare variants (minor allele frequency
      <=1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted
      damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence
      interval [CI] 1.68-7.35, p = 0.0002). Performing a meta-analysis with previously
      published data, we found that in a combined sample of 1,256 patients and 1,347
      controls from France and Belgium, the OR was 2.81 (95% CI 1.89-4.20, p = 3.60 *
      10(-7)). CONCLUSIONS: These results confirm that ABCA7 LOF variants are enriched
      in patients with AD and extend this finding to predicted damaging missense
      variants.

PMID- 27037233
TI  - Autoimmune encephalitis: A more treatable tragedy if diagnosed early.

PMID- 27037232
TI  - Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation.
AB  - OBJECTIVE: To generate a clinical and pathologic phenotype of patients carrying
      rare loss-of-function mutations in ABCA7, identified in a Belgian Alzheimer
      patient cohort and in an autosomal dominant family. METHODS: We performed a
      retrospective review of available data records, medical records, results of CSF
      analyses and neuroimaging studies, and neuropathology data. RESULTS: The mean
      onset age of the mutation carriers (n = 22) was 73.4 +/- 8.4 years with a wide
      age range of 36 (54-90) years, which was independent of APOE genotype and
      cerebrovascular disease. The mean disease duration was 5.7 +/- 3.0 years (range 2
      12 years). A positive family history was recorded for 10 carriers (45.5%). All
      patient carriers except one presented with memory complaints. The 4 autopsied
      brains showed typical immunohistochemical changes of late-onset Alzheimer
      disease. CONCLUSIONS: All patients carrying a loss-of-function mutation in ABCA7
      exhibited a classical Alzheimer disease phenotype, though with a striking wide
      onset age range, suggesting the influence of unknown modifying factors.

PMID- 27037234
TI  - Prevalence, characteristics, and survival of frontotemporal lobar degeneration
      syndromes.
AB  - OBJECTIVES: To estimate the lifetime risk, prevalence, incidence, and mortality
      of the principal clinical syndromes associated with frontotemporal lobar
      degeneration (FTLD) using revised diagnostic criteria and including intermediate
      clinical phenotypes. METHODS: Multisource referral over 2 years to identify all
      diagnosed or suspected cases of frontotemporal dementia (FTD), progressive
      supranuclear palsy (PSP), or corticobasal syndrome (CBS) in 2 UK counties
      (population 1.69 million). Diagnostic confirmation used current consensus
      diagnostic criteria after interview and reexamination. Results were adjusted to
      the 2013 European standard population. RESULTS: The prevalence of FTD, PSP, and
      CBS was 10.8/100,000. The incidence and mortality were very similar, at
      1.61/100,000 and 1.56/100,000 person-years, respectively. The estimated lifetime
      risk is 1 in 742. Survival following diagnosis varied widely: from PSP 2.9 years
      to semantic variant FTD 9.1 years. Age-adjusted prevalence peaked between 65 and
      69 years at 42.6/100,000: the age-adjusted prevalence for persons older than 65
      years is double the prevalence for those between 40 and 64 years. Fifteen percent
      of those screened had a relevant genetic mutation. CONCLUSIONS: Key features of
      this study include the revised diagnostic criteria with improved specificity and
      sensitivity, an unrestricted age range, and simultaneous assessment of multiple
      FTLD syndromes. The prevalence of FTD, PSP, and CBS increases beyond 65 years,
      with frequent genetic causes. The time from onset to diagnosis and from diagnosis
      to death varies widely among syndromes, emphasizing the challenge and importance
      of accurate and timely diagnosis. A high index of suspicion for FTLD syndromes is
      required by clinicians, even for older patients.

PMID- 27037235
TI  - Voltage-gated potassium channel antibodies: Game over.

PMID- 27037223
TI  - Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic
      Treatment of Smooth Muscle Disorders.
AB  - The smooth muscle cell directly drives the contraction of the vascular wall and
      hence regulates the size of the blood vessel lumen. We review here the current
      understanding of the molecular mechanisms by which agonists, therapeutics, and
      diseases regulate contractility of the vascular smooth muscle cell and we place
      this within the context of whole body function. We also discuss the implications
      for personalized medicine and highlight specific potential target molecules that
      may provide opportunities for the future development of new therapeutics to
      regulate vascular function. 

PMID- 27037236
TI  - Chemical synthesis of RNA with site-specific methylphosphonate modifications.
AB  - Methylphosphonate(mP)-modified RNA serves as valuable probe to evaluate
      biomolecular interactions between the nucleic acid backbone and binding partners,
      such as proteins or small molecules. Here, we describe an efficient workflow for
      the synthesis of RNA with a single mP modification in diastereomerically pure
      form. While the automated assembly of mP-modified RNA is straightforward, its
      deprotection under basic conditions is challenging; a carefully optimized step-by
      step procedure is provided. In addition, we demonstrate purification and
      separation strategies for the RP and SP-configurated RNA diastereomers using a
      combination of anion-exchange and reversed-phase HPLC, and comment on
      troubleshooting if their separation appears difficult. Furthermore, we
      demonstrate the stereochemical assignment of short RP and SP mP-modified RNA
      diastereomers based on 2D ROESY NMR spectroscopy and we report on the impact of
      the mP modification on thermal and thermodynamic stabilities of RNA-DNA hybrid
      and RNA-RNA duplexes.

PMID- 27037237
TI  - Corrigendum.

PMID- 27037240
TI  - Unraveling the Phenotypic Variability of Juvenile Idiopathic Arthritis across
      Races or Geographic Areas--Key to Understanding Etiology and Genetic Factors?

PMID- 27037239
TI  - Admission plasma glucose levels within the normal to mildly impaired range and
      the outcome of patients with acute coronary syndrome.
AB  - BACKGROUND: Elevated admission plasma glucose levels >140 mg/dl are associated
      with adverse clinical outcomes in both diabetic and non-diabetic patients
      admitted with acute coronary syndrome (ACS). We aimed to evaluate the association
      between admission plasma glucose levels <140 mg/dl and the outcome of non
      diabetic patients admitted with acute coronary syndrome. METHODS: The study
      population consisted of patients with acute coronary syndrome included in the
      Acute Coronary Syndrome Israeli Survey during 2000-2013. Diabetic patients were
      excluded. The primary endpoint was all-cause mortality at one year. RESULTS: The
      452 0 patients had a mean age of 61.7+/-13.5 years and were stratified into four
      quartiles according to admission plasma glucose (60-94, 95-105, 106-119, 120-140
      mg/dl). Patients with higher admission plasma glucose were older and included a
      higher percentage of smokers. In addition, the higher the glucose so also did
      they have a poorer risk factor profile including a higher body mass index, total
      and low-density lipoprotein cholesterol and triglyceride levels, and lower high
      density lipoprotein cholesterol levels. During the first year 5.2% of patients
      died. A comparison of one-year mortality according to admission plasma glucose
      quartiles demonstrated a significant and progressive increase in mortality risk
      as admission plasma glucose rose (3.5%, 4.1%, 6.1%, 6.4%, respectively, p=0.001).
      However, this association lost its clinical significance following a multivariate
      analysis ( p=0.08). CONCLUSIONS: High admission plasma glucose levels within the
      normal to mildly impaired range are associated with increased one-year mortality
      in non-diabetic acute coronary syndrome patients. However, the higher glucose
      level is probably not the cause for the adverse outcome but rather a marker for
      high risk. Our findings support the definition of 140 mg/dl as the cutoff for
      clinically acceptable admission glucose levels in patients with acute coronary
      syndrome.

PMID- 27037241
TI  - Pain Management for the Young Adult Rheumatology Patient in an Era of Medicinal
      Marijuana Legalization.

PMID- 27037238
TI  - Interplay between Fanconi anemia and homologous recombination pathways in genome
      integrity.
AB  - The Fanconi anemia (FA) pathway plays a central role in the repair of DNA
      interstrand crosslinks (ICLs) and regulates cellular responses to replication
      stress. Homologous recombination (HR), the error-free pathway for double-strand
      break (DSB) repair, is required during physiological cell cycle progression for
      the repair of replication-associated DNA damage and protection of stalled
      replication forks. Substantial crosstalk between the two pathways has recently
      been unravelled, in that key HR proteins such as the RAD51 recombinase and the
      tumour suppressors BRCA1 and BRCA2 also play important roles in ICL repair.
      Consistent with this, rare patient mutations in these HR genes cause FA
      pathologies and have been assigned FA complementation groups. Here, we focus on
      the clinical and mechanistic implications of the connection between these two
      cancer susceptibility syndromes and on how these two molecular pathways of DNA
      replication and repair interact functionally to prevent genomic instability.

PMID- 27037242
TI  - Minocycline-induced Cartilage Hyperpigmentation Mimicking Alkaptonuria in a
      Patient with Knee Pain.

PMID- 27037243
TI  - Defining Chronic Pain.

PMID- 27037244
TI  - Ms. A.M. Taylor, et al reply.

PMID- 27037245
TI  - Age and Comorbidities Influence Initial Treatment of Patients with Early
      Rheumatoid Arthritis.

PMID- 27037246
TI  - IgG4 Syndrome Presenting as Leptomeningitis in a Young Woman.

PMID- 27037247
TI  - Soluble CD163: A Novel Biomarker with Diagnostic and Therapeutic Implications in
      Autoimmune Diseases.

PMID- 27037248
TI  - Paramyxovirus Infection: Mortality and Morbidity in a Pediatric Intensive Care
      Unit.
AB  - OBJECTIVES: We investigated mortality and morbidity of patients admitted to a
      pediatric intensive care unit (PICU) with paramyxovirus infection. METHODS: A
      retrospective study between October 2002 and March 2015 of children with a
      laboratory-confirmed paramyxovirus infection was included. RESULTS: In all, 98
      (5%) PICU admissions were tested positive to have paramyxovirus infection
      (respiratory syncytial virus =  66, parainfluenza  =  27 and metapneumovirus  = 
      5). The majority of admissions were young patients (median age 1.05 years).
      Bacteremia and bacterial isolation in any site were present in 10% and 28%,
      respectively; 41% were mechanically ventilated, and 20% received inotropes. The
      three respiratory viruses caused similar mortality and morbidity in the PICU.
      Fatality (seven patients) was associated with malignancy, positive bacterial
      culture in blood, the use of mechanical ventilation, inotrope use, lower blood
      white cell count and higher C reactive protein (p  =  0.02-0.0005). Backward
      binary logistic regression for these variables showed bacteremia (odds ratio
      [OR]: 31.7; 95% CI: 2.3-427.8; p  =  0.009), malignancy (OR: 45.5; 95% CI: 1.4
      1467.7; p  =  0.031) and use of inotropes (OR: 15.0; 95% CI: 1.1-196.1; p  = 
      0.039) were independently associated with non-survival. March and July appeared
      to be the two peak months for PICU hospitalizations with paramyxovirus infection.
      CONCLUSIONS: Infections with paramyxoviruses account for 5% of PICU admissions
      and significant morbidity. Patient with premorbid history of malignancy and co
      morbidity of bacteremia are associated with non-survival. March and July appeared
      to be the two peak months for PICU admissions with paramyxoviruses.

PMID- 27037249
TI  - People lack awareness of link between alcohol and cancer, survey finds.

PMID- 27037250
TI  - Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity
      whose subcellular localization is different than those of dolichyl-phosphate
      dependent enzymes of the dolichol cycle.
AB  - Oligosaccharyl phosphates (OSPs) are hydrolyzed from oligosaccharide
      diphosphodolichol (DLO) during protein N-glycosylation by an uncharacterized
      process. An OSP-generating activity has been reported in vitro, and here we asked
      if its biochemical characteristics are compatible with a role in endoplasmic
      reticulum (ER)-situated DLO regulation. We demonstrate a Co(2+)-dependent DLO
      diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP.
      DLODP has a pH optimum of 5.5 and is inhibited by vanadate but not by NaF.
      Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of
      their alkyl chains correlating positively with inhibition potency. The
      diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and
      inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the
      diphosphomonoester solanesyl diphosphate. During subcellular fractionation of
      liver homogenates, DLODP codistributes with microsomal markers, and density
      gradient centrifugation revealed that the distribution of DLODP is closer to that
      of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than
      those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis
      in the ER. Therefore, a DLODP activity showing selectivity toward lipophilic
      diphosphodiesters such as DLO, and possessing properties distinct from other
      lipid phosphatases, is identified. Separate subcellular locations for DLODP
      action and DLO biosynthesis may be required to prevent uncontrolled DLO
      destruction.

PMID- 27037251
TI  - Is Expanded HIV Testing Associated with Earlier HIV Diagnosis? Results from an
      HIV Clinic in Guatemala City.
AB  - BACKGROUND: Most patients in Guatemala are diagnosed with advanced HIV disease.
      Patients that present late in the disease process may miss the morbidity and
      mortality benefits associated with early treatment and may unknowingly spread HIV
      to others. RESEARCH QUESTIONS: We examined trends in HIV detection and levels of
      immunosuppression at diagnosis from 2005 -2012 to determine if expanded HIV
      testing was associated with earlier detection of HIV. SETTING: This study was
      conducted at the Clinica Familiar Luis Angel Garcia (CFLAG), a major HIV center
      associated with one of Guatemala's two national hospitals. HIV testing expanded
      rapidly after 2007 due to grants from the Global Fund which allowed for routine
      prenatal testing. METHODS: This study examined existing hospital and clinic
      databases from to evaluate results from HIV tests performed, and baseline CD4
      cells/mm(3) on all patients newly diagnosed with HIV infection from 2005 to 2012.
      RESULTS: We found a decline in the number of HIV positive tests over the study
      period despite an increase in the total number of tests performed. Sixty-two
      percent of HIV infected individuals had AIDS at diagnosis. We observed a decrease
      in median CD4 cells/mm(3) among the prenatal testees and no change in non
      prenatal testees. DISCUSSION: Expanded HIV counseling and testing services in our
      clinic did not result in earlier HIV diagnosis.

PMID- 27037254
TI  - HER2 and HER3 in HPV+ and HPV- HNSCC--Letter.

PMID- 27037253
TI  - Molecular Pathways: Breaking the Epithelial Cancer Barrier for Chimeric Antigen
      Receptor and T-cell Receptor Gene Therapy.
AB  - Adoptive transfer of T cells genetically engineered to express a tumor-targeting
      chimeric antigen receptor (CAR) or T-cell receptor (TCR) can mediate cancer
      regression in some patients. CARs are synthetic single-chain proteins that use
      antibody domains to target cell surface antigens. TCRs are natural heterodimeric
      proteins that can target intracellular antigens through recognition of peptides
      bound to human leukocyte antigens. CARs have shown promise in B-cell malignancies
      and TCRs in melanoma, but neither approach has achieved clear success in an
      epithelial cancer. Treatment of epithelial cancers may be particularly
      challenging because of a paucity of target antigens expressed by carcinomas and
      not by important healthy tissues. In addition, epithelial cancers may be
      protected by inhibitory ligands and soluble factors in the tumor
      microenvironment. One strategy to overcome these negative regulators is to
      modulate expression of T-cell genes to enhance intrinsic T-cell function.
      Programmable nucleases, which can suppress inhibitory genes, and inducible gene
      expression systems, which can enhance stimulatory genes, are entering clinical
      testing. Other work is delineating whether control of genes for immune checkpoint
      receptors (e.g.,PDCD1, CTLA4) and cytokine and TCR signaling regulators
      (e.g.,CBLB, CISH, IL12, IL15) can increase the antitumor activity of therapeutic
      T cells.

PMID- 27037255
TI  - HER2 and HER3 in HPV+ and HPV- HNSCC--Response.

PMID- 27037256
TI  - Afatinib + Cetuximab First-line in EGFR-Mutant Lung Cancer--Letter.

PMID- 27037257
TI  - Measuring Toxicity in Phase I Clinical Trials--Letter.

PMID- 27037258
TI  - Mimicking the cardiac cycle in intact cardiomyocytes using diastolic and systolic
      force clamps; measuring power output.
AB  - AIMS: A single isolated cardiomyocyte is the smallest functional unit of the
      heart. Yet, all single isolated cardiomyocyte experiments have been limited by
      the lack of proper methods that could reproduce a physiological cardiac cycle. We
      aimed to investigate the contractile properties of a single cardiomyocyte that
      correctly mimic the cardiac cycle. METHODS AND RESULTS: By adjusting the
      parameters of the feedback loop, using a suitably engineered feedback system and
      recording the developed force and the length of a single rat cardiomyocyte during
      contraction and relaxation, we were able to construct force-length (FL) relations
      analogous to the pressure-volume (PV) relations at the whole heart level. From
      the cardiac loop graphs, we obtained, for the first time, the power generated by
      one single cardiomyocyte. CONCLUSION: Here, we introduce a new approach that by
      combining mechanics, electronics, and a new type optical force transducer can
      measure the FL relationship of a single isolated cardiomyocyte undergoing a
      mechanical loop that mimics the PV cycle of a beating heart.

PMID- 27037260
TI  - Medicinal Use of Marijuana: What School Nurses Need to Know.
AB  - The subject of medical marijuana is complex and currently of interest and concern
      to patients and health care providers. Legislators throughout the United States
      have passed state-specific laws and regulations that impact medical practice and
      the use of marijuana as a therapeutic modality. In November 2015, New Jersey
      became the first state to specifically allow the administration of medical
      marijuana for students and persons with developmental disabilities. The purpose
      of this article is to provide a frame of reference for school nurses and to
      encourage awareness of the implications for student health and relevant nursing
      interventions in the school setting. 

PMID- 27037259
TI  - Haemodynamic unloading reverses occlusive vascular lesions in severe pulmonary
      hypertension.
AB  - AIMS: An important pathogenic mechanism in the development of idiopathic
      pulmonary arterial hypertension is hypothesized to be a cancer-like cellular
      proliferation independent of haemodynamics. However, because the vascular lesions
      are inseparably coupled with haemodynamic stress, the fate of the lesions is
      unknown when haemodynamic stress is eliminated. METHODS AND RESULTS: We applied
      left pulmonary artery banding to a rat model with advanced pulmonary hypertension
      to investigate the effects of decreased haemodynamic stress on occlusive vascular
      lesions. Rats were given an injection of the VEGF blocker Sugen5416 and exposed
      to 3 weeks of hypoxia plus an additional 7 weeks of normoxia (total 10 weeks)
      (SU/Hx/Nx rats). The banding surgery to reduce haemodynamic stress to the left
      lung was done at 1 week prior to (preventive) or 5 weeks after (reversal) the
      SU5416 injection. All SU/Hx/Nx-exposed rats developed severe pulmonary
      hypertension and right ventricular hypertrophy. Histological analyses showed that
      the non-banded right lungs developed occlusive lesions including plexiform
      lesions with marked perivascular cell accumulation. In contrast, banding the left
      pulmonary artery not only prevented the development of but also reversed the
      established occlusive lesions as well as perivascular inflammation in the left
      lungs. CONCLUSION: Our results indicate that haemodynamic stress is prerequisite
      to the development and progression of occlusive neointimal lesions in this rat
      model of severe pulmonary hypertension. We conclude that perivascular
      inflammation and occlusive neointimal arteriopathy are driven by haemodynamic
      stress.

PMID- 27037261
TI  - Medicaid Managed Care: Unanswered Impact on School-Located Immunization Services.
AB  - Managed care coordination for Medicaid beneficiaries is being implemented in
      states across the country. Recently, 1.5 million Medicaid beneficiaries in five
      regions of Illinois began this transition. This article presents the findings of
      a study to learn if immunizations would continue to be a reimbursable service if
      provided to beneficiaries outside of the designated primary care setting. The
      findings revealed a lack of clarity among health plan representatives and billing
      personnel in how to obtain coverage information. Five contacted plans (25%)
      stated they were unable to verify coverage and unclear where to acquire this
      information. Similarly, six (30%) representatives could not answer the question
      and recommended calling the Illinois Department of Healthcare and Family Services
      hot line. Despite the potential benefit of improved coordination of care gained
      by transitioning to managed care entity model, this infrastructure change may
      inadvertently introduce barriers to services obtained outside the medical home,
      like school-located immunization.

PMID- 27037262
TI  - Sexual Health Concerns and American Teens.

PMID- 27037263
TI  - NHS England will strengthen rules for managing conflicts of interest in CCGs.

PMID- 27037264
TI  - NICE issues guidance to tackle multimorbidity.

PMID- 27037265
TI  - Is the CMS Hospital-Acquired Condition Reduction Program a Valid Measure of
      Hospital Performance?
AB  - In October 2014, the Centers for Medicare & Medicaid Services began reducing
      Medicare payments by 1% for the bottom performing quartile of hospitals under the
      Hospital-Acquired Condition Reduction Program (HACRP). A tight clustering of
      HACRP scores around the penalty threshold was observed resulting in 13.2% of
      hospitals being susceptible to a shift in penalty status related to single decile
      changes in the ranking of any one of the complication or infection measures used
      to compute the HACRP score. The HACRP score also was found to be significantly
      correlated with several hospital characteristics including hospital case mix
      index. This correlation was not confirmed when an alternative method of measuring
      hospital complication performance was used. The sensitivity of the HACRP
      penalties to small changes in performance and correlation of the HACRP score with
      hospital characteristics call into question the validity of the HACRP measure and
      method of risk adjustment.

PMID- 27037266
TI  - Changing Physician Behavior by Integrating a Risk-Adjusted Database Into a
      Quality Improvement Program.

PMID- 27037267
TI  - Incorporating Patient Acuity Rating Score Into Patient Handoffs and the
      Correlation With Rapid Responses and Unexpected ICU Transfers.
AB  - Handoffs and rapid response team (RRT) activations have been a focus for quality
      improvement in hospital medicine. This study aimed to incorporate a previously
      used scoring system (1-7) for severity of illness on initial encounter as a
      handoff adjunct and to determine its impact on the number of RRTs and intensive
      care unit transfers. The Patient Acuity Rating (PAR) scale correlates with
      subsequent RRTs and transfers to a higher level of care, with higher scores
      leading to increased rates of RRTs and transfers. Patients who experienced an RRT
      at any time (mean score 4.69), within 24 hours (4.74), or an unplanned transfer
      (5.16) had higher PAR scores on assessment than those who did not (4.02; all P <
      .05). There was an increased likelihood of RRTs and transfers with scores of 6 or
      higher. There was no reduction in the quantity of RRTs or unplanned intensive
      care unit transfers comparing preintervention and postintervention data.

PMID- 27037268
TI  - Association Between High Ambient Temperature and Risk of Stillbirth in
      California.
AB  - Recent studies have linked elevated apparent temperatures with adverse birth
      outcomes, such as preterm delivery, but other birth outcomes have not been well
      studied. We examined 8,510 fetal deaths (>=20 weeks' gestation) to estimate their
      association with mean apparent temperature, a combination of temperature and
      humidity, during the warm season in California (May-October) from 1999 to 2009.
      Mothers whose residential zip codes were within 10 km of a meteorological monitor
      were included. Meteorological data were provided by the California Irrigation
      Management Information System, the US Environmental Protection Agency, and the
      National Climatic Data Center, while the California Department of Public Health
      provided stillbirth data. Using a time-stratified case-crossover study design, we
      found a 10.4% change (95% confidence interval: 4.4, 16.8) in risk of stillbirth
      for every 10 degrees F (5.6 degrees C) increase in apparent temperature
      (cumulative average of lags 2-6 days). Risk varied by maternal race/ethnicity and
      was greater for younger mothers, less educated mothers, and male fetuses. The
      highest risks were observed during gestational weeks 20-25 and 31-33. No
      associations were found during the cold season (November-April), and the observed
      associations were independent of air pollutants. This study adds to the growing
      body of literature identifying pregnant women and their fetuses as subgroups
      vulnerable to heat exposure.

PMID- 27037269
TI  - Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health
      Initiative.
AB  - Cadmium is a widespread heavy metal pollutant that may act as an exogenous
      estrogenic hormone. Environmental cadmium exposure has been associated with risk
      of breast cancer in retrospective studies. We prospectively assessed the
      relationship between cadmium exposure, evaluated by creatinine-normalized urinary
      cadmium concentration, and invasive breast cancer among 12,701 postmenopausal
      women aged >=50 years in a Women's Health Initiative study of bone mineral
      density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of
      invasive breast cancer and 1,050 comparison women were identified for a case
      cohort analysis. Multivariable Cox regression was used to calculate hazard ratios
      and 95% confidence intervals. Risk of breast cancer was not associated with
      urinary cadmium parameterized either in quartiles (comparing highest quartile
      with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for
      trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher
      urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval:
      0.86, 1.03). We did not observe an association between urinary cadmium and breast
      cancer risk in any subgroup examined, including never smokers and women with body
      mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in
      both estrogen receptor-positive and estrogen receptor-negative tumors. Our
      results do not support the hypothesis that environmental cadmium exposure is
      associated with risk of postmenopausal breast cancer.

PMID- 27037270
TI  - Comparison of Calipers for Matching on the Disease Risk Score.
AB  - Previous studies have compared calipers for propensity score (PS) matching, but
      none have considered calipers for matching on the disease risk score (DRS). We
      used Medicare claims data to perform 3 cohort studies of medication initiators: a
      study of raloxifene versus alendronate in 1-year nonvertebral fracture risk, a
      study of cyclooxygenase 2 inhibitors versus nonselective nonsteroidal
      antiinflammatory medications in 6-month gastrointestinal bleeding, and a study of
      simvastatin + ezetimibe versus simvastatin alone in 6-month cardiovascular
      outcomes. The study periods for each cohort were 1998 through 2005, 1999 through
      2002, and 2004 through 2005, respectively. In each cohort, we calculated 1) a
      DRS, 2) a prognostic PS which included the DRS as the independent variable in a
      PS model, and 3) the PS for each patient. We then nearest-neighbor matched on
      each score in a variable ratio and a fixed ratio within 8 calipers based on the
      standard deviation of the logit and the natural score scale. When variable ratio
      matching on the DRS, a caliper of 0.05 on the natural scale performed poorly when
      the outcome was rare. The prognostic PS did not appear to offer any consistent
      practical benefits over matching on the DRS directly. In general, logit-based
      calipers or calipers smaller than 0.05 on the natural scale performed well when
      DRS matching in all examples.

PMID- 27037271
TI  - Evaluating Approaches for the Diagnosis of Hemodialysis Catheter-Related
      Bloodstream Infections.
AB  - BACKGROUND AND OBJECTIVES: Guideline-recommended diagnostic criteria for
      hemodialysis (HD) catheter-related bloodstream infections (CRBSIs) are based on
      data from indwelling central catheters in patients not on HD and non-HD
      situations, and upon which peripheral vein cultures are the gold standard. We
      aimed to examine the validity of these criteria in patients on HD. DESIGN,
      SETTINGS, PARTICIPANTS, & MEASUREMENTS: Adult patients on in-center HD using
      catheters were prospectively followed from 2011 to 2014 at a large academic-based
      HD facility (Toronto, Canada). When a CRBSI was suspected, blood culture sets
      were obtained from four sites (peripheral vein, both catheter hubs, and HD
      circuit) to determine the guideline-recommended differential time to positivity
      (DTTP). DTTP criteria were met when catheter hub cultures turned positive >=120
      minutes before peripheral vein cultures. The sensitivity, specificity, and
      accuracy were first calculated using peripheral vein cultures as the gold
      standard and then these same calculations were repeated with additional
      information, including exit site/catheter tip and HD circuit cultures, as the
      true gold standard. The feasibility of obtaining peripheral vein cultures was
      determined. RESULTS: Of 178 suspected CRBSIs, 100 had peripheral vein blood
      cultures. Using the true gold standard, sensitivity, specificity, and accuracy of
      blood culture results were highest in samples from the HD circuit (93.5%, 100%,
      and 95%, respectively). The guideline recommended combination of peripheral vein
      and arterial hub blood cultures was the least sensitive, specific, and accurate
      (91.7%, 93.1%, and 92.7%, respectively). The diagnostic criteria using measured
      DTTP were met in less than one third of events. CONCLUSIONS: In patients on HD,
      blood culture results are the most sensitive, specific, and accurate for
      diagnosing CRBSIs when taken from the HD circuit and the venous catheter hub, and
      blood culture results are the least sensitive, specific, and accurate in any
      combination with peripheral vein cultures. The DTTP does not increase diagnostic
      accuracy, reducing the necessity for venipuncture and its potential vein damage.
      Future guidelines should consider the applicability of criterion on specific
      patient populations and tailor them accordingly.

PMID- 27037272
TI  - Update on Ethical Issues in Pediatric Dialysis: Has Pediatric Dialysis Become
      Morally Obligatory?
AB  - Improvements in pediatric dialysis over the past 50 years have made the decision
      to proceed with dialysis straightforward for the majority of pediatric patients.
      For certain groups, however, such as children with multiple comorbid conditions,
      children and families with few social and economic resources, and neonates and
      infants, the decision of whether to proceed with dialysis remains much more
      controversial. In this review, we will examine the best available data regarding
      the outcomes of dialysis in these populations and analyze the important ethical
      considerations that should guide decisions regarding dialysis for these patients.
      We conclude that providers must continue to follow a nuanced and individualized
      approach in decision making for each child and to recognize that, regardless of
      the decision reached about dialysis, there is a continued duty to care for
      patients and families to maximize the remaining quality of their lives.

PMID- 27037273
TI  - Optimal Approach for the Diagnosis of Hemodialysis Catheter-Related Bacteremia.

PMID- 27037274
TI  - Evaluation of two commercial carbapenemase gene assays, the Rapidec Carba NP test
      and the in-house Rapid Carba NP test, on bacterial cultures.

PMID- 27037275
TI  - Enhanced protection against renal ischemia-reperfusion injury with combined
      melatonin and exendin-4 in a rodent model.
AB  - We tested the hypothesis that combined treatment with melatonin, an anti-oxidant,
      and exendin-4, an anti-inflammatory agent, was superior to either alone for
      protecting the kidney from ischemia-reperfusion (IR) injury. Male adult Sprague
      Dawley rats (n=40) were equally divided into group 1 (sham-operated control),
      group 2 (IR only, IR=1h/72h), group 3 (IR-exendin-4, 10 ug/kg at 30 min, 24 h, 48
      h after IR procedure), group 4 (IR-melatonin, i.p. 50 mg at 30 min, then 20 mg at
      6 and 18 h after IR procedure), and group 5 (combined IR-exendin-4-melatonin).
      All animals were sacrificed by 72 h after IR/sham procedure. The results showed
      that the kidney injury score, plasma creatinine, and blood urea nitrogen (BUN)
      levels were highest in group 2 and lowest in group 1, significantly higher in
      groups 3 and 4 than those in group 5 and significantly higher in group 3 than
      those in group 4 (all p < 0.001). The protein expressions of inflammatory (toll
      like receptor 4, inducible nitric oxide synthase, interleukin-1beta), apoptotic
      (mitochondrial Bax, cleaved caspase-3 and poly(ADP-ribose) polymerase, p53),
      podocyte integrity (E-cadherin, P-cadherin), and cell survival
      (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) biomarkers, as
      well the podocyte dysfunction biomarkers (Wnt1/Wnt4/beta-catenin) displayed a
      pattern identical to that of creatinine level among the five groups (all p <
      0.001). Microscopic findings demonstrated that podocyte dysfunction
      (Wnt1/Wnt4/beta-catenin expression) and inflammatory (CD14 and F4/80-positively
      stained cells) biomarkers exhibited an identical pattern, whereas that of
      antioxidant (HO-1(+), NQO-1(+) cells) biomarkers showed an opposite pattern
      compared to that of creatinine level among the five groups (all p < 0.001).
      Combined melatonin-exendin-4 therapy offered an additional benefit in protecting
      the kidney from acute IR injury.

PMID- 27037276
TI  - A novel in vitro platform for the study of SN38-induced mucosal damage and the
      development of Toll-like receptor 4-targeted therapeutic options.
AB  - Tight junction and epithelial barrier disruption is a common trait of many
      gastrointestinal pathologies, including chemotherapy-induced gut toxicity.
      Currently, there are no validated in vitro models suitable for the study of
      chemotherapy-induced mucosal damage that allow paralleled functional and
      structural analyses of tight junction integrity. We therefore aimed to determine
      if a transparent, polyester membrane insert supports a polarized T84 monolayer
      with the phenotypically normal tight junctions. T84 cells (passage 5-15) were
      seeded into either 0.6 cm(2), 0.4 um pore mixed-cellulose transwell hanging
      inserts or 1.12 cm(2), 0.4 um pore polyester transwell inserts at varying
      densities. Transepithelial electrical resistance was measured daily to assess
      barrier formation. Immunofluoresence for key tight junction proteins (occludin,
      zonular occludens-1, claudin-1) and transmission electron microscopy were
      performed to assess tight junction integrity, organelle distribution, and
      polarity. Reverse transcription-polymerase chain reaction was performed to
      determine expression of toll-like receptor 4 (TLR4). Liquid chromatography was
      also conducted to assess SN38 degradation in this model. Polyester membrane
      inserts support a polarized T84 phenotype with functional tight junctions in
      vitro. Transmission electron microscopy indicated polarity, with apico-laterally
      located tight junctions. Immunofluorescence showed membranous staining for all
      tight junction proteins. No internalization was evident. T84 cells expressed
      TLR4, although this was significantly lower than levels seen in HT29 cells (P =
      .0377). SN38 underwent more rapid degradation in the presence of cells (-76.04 +/
      1.86%) compared to blank membrane (-48.39 +/- 4.01%), indicating metabolic
      processes. Polyester membrane inserts provide a novel platform for paralleled
      functional and structural analysis of tight junction integrity in T84 monolayers.
      T84 cells exhibit the unique ability to metabolize SN38 as well as expressing
      TLR4, making this an excellent platform to study clinically relevant therapeutic
      interventions for SN38-induced mucosal damage by targeting TLR4.

PMID- 27037277
TI  - Phospholipid transfer protein deficiency in mice impairs macrophage reverse
      cholesterol transport in vivo.
AB  - Phospholipid transfer protein is expressed in various cell types and secreted
      into plasma, where it transfers phospholipids between lipoproteins and modulates
      the composition of high-density lipoprotein particles. Phospholipid transfer
      protein deficiency in vivo can lower high-density lipoprotein cholesterol level
      significantly and impact the biological quality of high-density lipoprotein.
      Considering high-density lipoprotein was a critical determinant for reverse
      cholesterol transport, we investigated the role of systemic phospholipid transfer
      protein deficiency in macrophage reverse cholesterol transport in vivo After the
      littermate phospholipid transfer protein KO and WT mice were fed high-fat diet
      for one month, they were injected intraperitoneally with (3)H-cholesterol-labeled
      and acLDL-loaded macrophages. Then the appearance of (3)H-tracer in plasma,
      liver, bile, intestinal wall, and feces over 48 h was determined. Plasma lipid
      analysis indicated phospholipid transfer protein deficiency lowered total
      cholesterol, high-density lipoprotein-C and apolipoprotein A1 levels
      significantly but increased triglyceride level in mice. The isotope tracing
      experiment showed (3)H-cholesterol of plasma was decreased by 68% for male and
      62% for female, and (3)H-tracer of bile was decreased by 37% for male and 21% for
      female in phospholipid transfer protein KO mice compared with WT mice. However,
      there was no difference in liver, and (3)H-tracer of intestinal wall was
      increased by 43% for male and 27% for female. Finally, (3)H-tracer of fecal
      excretion in phospholipid transfer protein KO mice was reduced significantly by
      36% for male and 43% for female during 0-24 h period, but there was no
      significant difference during 24-48 h period. Meanwhile, Western Blot analysis
      showed the expressions of reverse cholesterol transport -related protein liver X
      receptor alpha (LXRalpha), ATP binding cassette transporter A1, and cholesterol
      7alpha-hydroxylase A1 were upregulated in liver of phospholipid transfer protein
      KO mice compared with WT mice. These data reveal that systemic phospholipid
      transfer protein deficiency in mice impairs macrophage-specific reverse
      cholesterol transport in vivo.

PMID- 27037278
TI  - Featured Article: Accelerated decline of physical strength in peroxiredoxin-3
      knockout mice.
AB  - As a member of peroxiredoxin family, peroxiredoxin-3 plays a major role in the
      control of mitochondrial level of reactive oxygen species. During the breeding of
      experimental mice, we noticed that the peroxiredoxin-3 knockout mice were
      listless with aging. In the present study, we compared the swimming exercise
      performance and oxidative status between peroxiredoxin-3 knockout mice (n = 15)
      and wild-type littermates (n = 15). At the age of 10 months, the physical
      strength of peroxiredoxin-3 knockout mice was much lower than the wild-type
      littermates. Increased oxidative damage and decreased mitochondrial DNA copy
      number of the animal skeletal muscles were observed in peroxiredoxin-3 knockout
      mice as compared to that in the wild-type littermates. In addition, we found
      increased apoptotic cells in the brains of peroxiredoxin-3 knockout mice. Our
      results suggest that the deficiency of peroxiredoxin-3 induces accelerated
      oxidative stress and mitochondrial impairment, resulting in the decrease of
      energy supply and cellular activities. Peroxiredoxin-3 might be involved in the
      inhibition of aging process.

PMID- 27037279
TI  - Evaluation of a bilayered, micropatterned hydrogel dressing for full-thickness
      wound healing.
AB  - Nearly 12 million wounds are treated in emergency departments throughout the
      United States every year. The limitations of current treatments for complex, full
      thickness wounds are the driving force for the development of new wound treatment
      devices that result in faster healing of both dermal and epidermal tissue. Here,
      a bilayered, biodegradable hydrogel dressing that uses microarchitecture to guide
      two key steps in the proliferative phase of wound healing, re-epithelialization,
      and revascularization, was evaluated in vitro in a cell migration assay and in
      vivo in a bipedicle ischemic rat wound model. Results indicate that the
      SharkletTM-micropatterned apical layer of the dressing increased artificial wound
      coverage by up to 64%, P = 0.024 in vitro. In vivo evaluation demonstrated that
      the bilayered dressing construction enhanced overall healing outcomes
      significantly compared to untreated wounds and that these outcomes were not
      significantly different from a leading clinically available wound dressing.
      Collectively, these results demonstrate high potential for this new dressing to
      effectively accelerate wound healing.

PMID- 27037280
TI  - Chelidonic acid evokes antidepressant-like effect through the up-regulation of
      BDNF in forced swimming test.
AB  - Depression is usually accompanied by neuro-inflammatory reactions. Chelidonic
      acid, in particular, has shown anti-inflammatory effects. The objective of this
      study was to evaluate the anti-depressant effects of chelidonic acid and to
      discuss the potential mechanisms of a forced swimming test. Chelidonic acid was
      administered orally once a day for 14 days. On the 14th day, chelidonic acid
      resulted in a significant decrease in immobility time during the forced swimming
      test without alteration of locomotor activity, in an open field test. Chelidonic
      acid also increased the number of nissl bodies in the hippocampus. Brain-derived
      neurotrophic factor expression and extracellular signal-regulated protein kinase
      phosphorylation in the hippocampus were up-regulated by the administration of
      chelidonic acid. Chelidonic acid administration significantly increased the mRNA
      expression of hippocampal estrogen receptor-beta. The levels of hippocampal
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were effectively
      attenuated by the administration of chelidonic acid. In addition, chelidonic acid
      significantly increased the levels of 5-hydroxytryptamine (serotonin), dopamine,
      and norepinephrine compared with those levels for the mice that were administered
      distilled water in the hippocampus. These results suggest that chelidonic acid
      might serve as a new therapeutic strategy for the regulation of depression
      associated with inflammation.

PMID- 27037281
TI  - Cardioprotective effects of sitagliptin against doxorubicin-induced
      cardiotoxicity in rats.
AB  - There is a large body of evidence suggesting that inhibitors of dipeptidyl
      peptidase-4, such as sitagliptin, may exhibit beneficial effects against
      different inflammatory disorders. This investigation was conducted to elucidate
      the potential ability of sitagliptin to counteract the injurious effects of
      doxorubicin in cardiac tissue. Male Wistar rats were pretreated with sitagliptin
      for 10 days then treated with a single dose of doxorubicin (20 mg/kg, i.p).
      Electrocardiography, biochemical estimation of serum and tissue markers, and
      histo- and immunopathological examinations were done. Results have shown that
      supplementation with sitagliptin resulted in significant improvement of cardiac
      function with contaminant decrease in serum markers of doxorubicin-induced
      cardiotoxicity. These results were supported by the histopathological results.
      Furthermore, a marked protection against oxidative stress was evident through
      reduction of lipid peroxidation and prevention of reduced glutathione content
      depletion and superoxide dismutase activity reduction in cardiac tissue of rats
      pretreated with sitagliptin in combination with doxorubicin. Moreover,
      sitagliptin ameliorated the activation of nuclear factor kappa-B and the release
      of inflammatory cytokines, tumour necrosis factor-alpha and nitric oxide.
      Finally, sitagliptin attenuated doxorubicin-induced increase in the expression of
      pro-apoptotic protein Bax and in the apoptotic marker, caspase-3. Collectively,
      these data indicate that sitagliptin pretreatment could alleviate doxorubicin
      induced cardiotoxicity via reducing oxidative damage and its subsequent
      inflammation and apoptosis.

PMID- 27037282
TI  - Clinical Practices in Collegiate Concussion Management.
AB  - BACKGROUND: In recent years, sports leagues and sports medicine experts have
      developed guidelines for concussion management. The extent to which current
      clinical practice is consistent with guideline recommendations is unclear. At the
      collegiate level, there have been few examinations of concussion management
      practices and the extent to which meaningful differences across divisions of
      competition exist. PURPOSE: The purposes of this study were to (1) examine
      current practices in concussion diagnosis and management at National Collegiate
      Athletic Association (NCAA) member colleges, (2) explore the extent to which
      current practices reflect current recommendations for concussion diagnosis and
      management, and (3) determine whether there are differences in management
      patterns across divisions of competition. DESIGN: Descriptive epidemiology study.
      METHODS: An electronic questionnaire was sent to sports medicine clinicians at
      all NCAA member colleges during September and October 2013. Clinicians were asked
      about baseline assessments, diagnosis and management practices, return-to-play
      protocols, the perceived prevalence of underdiagnosis, and basic demographic
      information. RESULTS: Approximately 30% (n = 866) of contacted clinicians,
      representing nearly 50% (n = 527) of NCAA member colleges, responded to the
      questionnaire. Preparticipation baseline examinations were administered at the
      majority of schools (95%), but most (87.5%) administered baseline assessments
      only to selected high-risk athletes. Computerized neurocognitive testing and
      balance assessments were most commonly used as preseason baseline and postinjury
      assessments. Multimodal examination in line with NCAA and other guidance was used
      only at a minority of institutions. Athletic trainers most commonly administered
      and interpreted the preseason baseline examination. Most clinicians reported that
      their institutions' practices were in line with NCAA guidelines during the first
      24 hours of an athlete's concussion diagnosis, with exact percentages varying
      across measures. Differences across divisions of competition included shorter
      return-to-play time at Division I schools than Division III schools (9.13 vs
      10.31 days, respectively) and more frequently referring concussed athletes to a
      physician within 24 hours of diagnosis at Division I schools. CONCLUSION:
      Concussion management at many colleges in the United States incorporates elements
      recommended by current guidelines; however, there is room to improve. Increasing
      the use of a multimodal baseline and postinjury examination will elevate the
      concussion care provided to college athletes and better align with best practice
      guidance.

PMID- 27037283
TI  - Dynamic Hip Kinematics During the Golf Swing After Total Hip Arthroplasty.
AB  - BACKGROUND: Although most surgeons allow their patients to play golf after total
      hip arthroplasty (THA), the effect on the implant during the golf swing is still
      unclear. PURPOSE: To evaluate hip kinematics during the golf swing after THA.
      STUDY DESIGN: Descriptive laboratory study. METHODS: Eleven hips in 9 patients
      who underwent primary THA were analyzed. All patients were right-handed
      recreational golfers, and these 11 hips included 6 right hips and 5 left hips.
      Periodic radiographic images of the golf swing were taken using a flat-panel x
      ray detector. Movements of the hip joint and components were assessed using 3
      dimensional-to-2-dimensional model-to-image registration techniques. Liner-to
      neck contact and translation of the femoral head with respect to the acetabular
      cup (cup-head translation) were examined. Hip kinematics, orientation of
      components, and maximum cup-head translation were compared between patients with
      and without liner-to-neck contact. RESULTS: On average, the golf swing produced
      approximately 50 degrees  of axial rotation in both lead and trail hips. Liner-to
      neck contact was observed in 4 hips with elevated rim liners (2 lead hips and 2
      trail hips) at maximum external rotation. Neither bone-to-bone nor bone-to
      implant contact was observed at any phases of the golf swing in any of the hips.
      Four hips with liner-to-neck contact had significantly larger maximum external
      rotation (37.9 degrees  +/- 7.0 degrees  vs 20.6 degrees  +/- 9.9 degrees ,
      respectively; P = .01) and more cup anteversion (26.5 degrees  +/- 6.1 degrees 
      vs 10.8 degrees  +/- 8.9 degrees , respectively; P = .01) than hips without liner
      to-neck contact. No significant differences between hips with and without contact
      were found for cup inclination (42.0 degrees  +/- 2.5 degrees  vs 38.1 degrees 
      +/- 5.5 degrees , respectively; P = .22), combined anteversion (45.3 degrees  +/-
      8.9 degrees  vs 51.4 degrees  +/- 7.9 degrees , respectively; P = .26), or
      maximum cup-head translation (1.3 +/- 0.3 mm vs 1.5 +/- 0.4 mm, respectively; P =
      .61). CONCLUSION: In this analysis, the golf swing did not produce excessive hip
      rotation or cup-head translation in any hips. However, liner-to-neck contact
      during the golf swing was observed in 36% of the hips, with unknown effects on
      the long-term results. CLINICAL RELEVANCE: Golf is an admissible sport after THA
      because dynamic hip stability was observed. However, the implant position,
      especially cup anteversion and the use of elevated rim liners, promoted liner-to
      neck contact.

PMID- 27037284
TI  - Incidence Rate and Results of the Surgical Treatment of Pectoralis Major Tendon
      Ruptures in Active-Duty Military Personnel.
AB  - BACKGROUND: Pectoralis major tendon ruptures are commonly described as rare
      injuries affecting men between 20 and 40 years of age, with generally excellent
      results after surgical repair. However, this perception is based on a relatively
      small number of case series and prospective studies in the orthopaedic
      literature. PURPOSE: To determine the incidence of pectoralis major tendon
      ruptures in the active-duty military population and the demographic risk factors
      for a rupture and to describe the outcomes of surgical treatment. STUDY DESIGN:
      Case control study; Level of evidence, 3. METHODS: We utilized the Military
      Health System Data Repository (MDR) to identify all active-duty military
      personnel surgically treated for a pectoralis major tendon rupture between
      January 2012 and December 2014. Electronic medical records were searched for
      patients' demographic information, injury characteristics, and postoperative
      complications and outcomes. Risk factors for a rupture were calculated using
      Poisson regression, based on population counts obtained from the MDR. Risk
      factors for a postoperative complication, the need for revision surgery, and the
      inability to continue with active duty were determined using univariate analysis
      and multivariate logistic regression. RESULTS: A total of 291 patients met
      inclusion criteria. The mean patient age was 30.5 years, all patients were male,
      and the median follow-up period was 18 months. The incidence of injuries was 60
      per 100,000 person-years over the study period. Risk factors for a rupture
      included service in the Army, junior officer or junior enlisted rank, and age
      between 25 and 34 years. White race and surgery occurring >6 weeks after injury
      were significant risk factors for a postoperative complication. Among the 214
      patients with a minimum of 12 months' clinical follow-up, 95.3% were able to
      return to military duty. Junior officer/enlisted status was a significant risk
      factor for failure to return to military duty. CONCLUSION: Among military
      personnel, Army soldiers and junior officer/enlisted rank were at highest risk of
      pectoralis major tendon ruptures, and junior personnel were at highest risk of
      being unable to return to duty after surgical treatment. Although increasing time
      from injury to surgery was not a risk factor for treatment failure or inability
      to return to duty, it did significantly increase the risk of a postoperative
      complication.

PMID- 27037285
TI  - Building a Thriving Nation: 21st-Century Vision and Practice to Advance Health
      and Equity.
AB  - It is a great time for prevention. As the United States explores what health in
      our country should look like, it is an extraordinary time to highlight the role
      of prevention in improving health, saving lives, and saving money. The Affordable
      Care Act's investment in prevention has spurred innovation by communities and
      states to keep people healthy and safein the first place This includes growing
      awareness that community conditions are critical in determining health and that
      there is now a strong track record of prevention success. Community prevention
      strategies create lasting changes by addressing specific policies and practices
      in the environments and institutions that shape our lives and our health-from
      schools and workplaces to neighborhoods and government. Action at the community
      level also fosters health equity-the opportunity for every person to achieve
      optimal health regardless of identity, neighborhood, ability, or social status
      and is often the impetus for national-level decisions that vitally shape the well
      being of individuals and populations. 

PMID- 27037287
TI  - Karen Denard Goldman, PhD, MCHES (1949-2014).

PMID- 27037288
TI  - ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM
      checkpoint signaling.

PMID- 27037286
TI  - Psychosocial Implications of Homophobia and HIV Stigma in Social Support
      Networks: Insights for High-Impact HIV Prevention Among Black Men Who Have Sex
      With Men.
AB  - Black men who have sex with men (BMSM) bear an increasingly disproportionate
      burden of HIV in the United States. The Centers for Disease Control and
      Prevention recommends high-impact combination prevention for populations at high
      risk for HIV infection, such as BMSM. However, few scholars have considered the
      types of behavioral interventions that combined with biomedical prevention could
      prove effective for mitigating the epidemic among BMSM. Between June 2013 and May
      2014, we conducted three in-depth interviews each with 31 BMSM, interviews with
      17 community stakeholders, and participant observation in New York City to
      understand the sociocultural and structural factors that may affect the
      acceptance of and adherence to oral preexposure prophylaxis among BMSM and to
      inform an adherence clinical trial. BMSM and community leaders frequently
      described condomless sex as a consequence of psychosocial factors and economic
      circumstances stemming from internalized homophobia resulting from rejection by
      families and religious groups. BMSM revealed that internalized homophobia and HIV
      stigma resulted in perceived lack of self- and community efficacy in accepting
      and adhering to preexposure prophylaxis. Our results indicate that addressing
      internalized homophobia and fostering emotional social support in peer networks
      are key elements to improve the effectiveness of combination prevention among
      BMSM. 

PMID- 27037289
TI  - Study Abroad Programs.

PMID- 27037290
TI  - President's Message: Transcultural Nurses: Do No Harm.

PMID- 27037291
TI  - Regenerative Rehabilitation and Genomics: Frontiers in Clinical Practice.

PMID- 27037292
TI  - Program Director's Response.

PMID- 27037293
TI  - A Special Regenerative Rehabilitation and Genomics Letter: Is There a "Hope"
      Molecule?

PMID- 27037294
TI  - Bilateral adrenal masses: a single-centre experience.
AB  - BACKGROUND: Bilateral adrenal masses may have aetiologies like hyperplasia and
      infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may
      have coexisting hypocortisolism. Bilateral tumours are likely to have
      hereditary/syndromic associations. The data on clinical profile of bilateral
      adrenal masses are limited. AIMS: To analyse clinical, biochemical and
      radiological features, and management outcomes in patients with bilateral adrenal
      masses. METHODS: Retrospective analysis of 70 patients with bilateral adrenal
      masses presenting to a single tertiary care endocrine centre from western India
      (2002-2015). RESULTS: The most common aetiology was pheochromocytoma (40%),
      followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%),
      metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral
      macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation
      was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years)
      compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting
      symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal
      pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%).
      The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas
      all cases of metastasis had abdominal pain. Mean size of adrenal masses was the
      largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis
      (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with
      pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in
      tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001).
      CONCLUSION: In evaluation of bilateral adrenal masses, age at presentation,
      presenting symptoms, lesion size, and biochemical features are helpful in
      delineating varied underlying aetiologies.

PMID- 27037295
TI  - Reply to the letter to the editor 'Insertion of central venous catheters (CVCs):
      any changes in the past ten years' by Biffi et al.

PMID- 27037296
TI  - BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian
      cancer.
AB  - The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the
      treatment of germline BRCA mutation-associated ovarian cancer, which represents
      ~15% of HGS cases, has recently led to European Medicines Agency and food and
      drug administration approval of olaparib. Accumulating evidence suggests that
      PARP inhibitors may have a wider application in the treatment of sporadic ovarian
      cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous
      recombination deficiency (HRD) through mechanisms including germline BRCA
      mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review,
      we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian
      cancer. There is accumulating evidence for routine somatic BRCA mutation testing,
      but the relevance of BRCA epigenetic modifications is less clear. We explore the
      challenges that need to be addressed if the full potential of these markers of
      HRD is to be utilised in clinical practice.

PMID- 27037297
TI  - Severe exacerbation or manifestation of primary disease related to nivolumab in
      non-small-cell lung cancer patients with poor performance status or brain
      metastases.

PMID- 27037298
TI  - Alteration of redox status by commonly used antimalarial drugs in the north
      western region of Nigeria.
AB  - This study was designed to investigate the alteration of redox status by commonly
      used antimalarials in Nigeria. Drugs used were artemisinin, artesunate,
      chloroquine, coartem and quinine at the final concentrations of 0.5-8.0 mg/mL.
      Blood samples were collected from malarial patients and apparently healthy humans
      for comparison. Reduced glutathione, catalase, superoxide dismutase (SOD)
      activities, protein content and lipid peroxidation were determined. All drugs
      significantly ( p < 0.05) increases the protein level relative to control in
      normal blood, whereas in the infected, a significant ( p < 0.05) reduction was
      observed. In normal blood, the antimalarials dose dependently decreased ( p <
      0.05) SOD and catalase activities with significant ( p < 0.05) increase in the
      infected. The level of glutathione in normal blood significantly ( p < 0.05)
      increases as compared with control, whereas in the infected, similar observation
      was made except that the levels were less, relative to control sample.
      Malondialdehyde level significantly ( p < 0.05) increases with increase in drugs
      concentration even though less than the level in the control with few exceptions.
      These effects were dose dependent and more pronounced in non-malarial conditions.
      Commonly used antimalarials might alter the redox status in both healthy and non
      healthy subjects thereby inducing oxidative stress.

PMID- 27037299
TI  - Cerebral oxygenation and sympathetic responses to smoking in young and middle
      aged smokers.
AB  - This study examined the effects of acute tobacco smoking on cerebral oxygenation
      and autonomic function in 28 male, habitual smokers of shorter young smokers
      (YSM) or longer middle-aged smokers (MSM) smoking history. Following baseline
      testing, participants undertook a smoking protocol involving the consumption of
      two cigarettes within 15 min. Measures of cerebral oxygenation and autonomic
      function were collected before, during, and 0 min, 30 min, 1 h, and 4 h post
      smoking. Tissue saturation index (TSI) for MSM was greater than YSM during
      cigarette consumption ( p < 0.05). Moreover, MSM observed significant within
      group changes for TSI during and post-cigarette consumption ( p < 0.05). Further,
      MSM observed an increase in low frequency (LF) band from 30 min to 1 h post
      consumption, followed by a decline, whereas elevations above MSM were observed in
      YSM at 4 h ( p < 0.05). Both MSM and YSM showed a decrease in high-frequency (HF)
      band post-cigarette, while increased LF/HF ratio post-consumption was observed in
      YSM. A decline in the standard deviation of RR intervals, post-cigarette
      consumption was evident in MSM ( p < 0.05). Moreover, the root mean square of RR
      interval in both groups similarly decreased following cigarette consumption ( p <
      0.05). Acute smoking affects heart rate variability, suggestive of vagal
      withdrawal, and maybe indicate an effect of smoking history. Additionally,
      prolonged smoking history alters cerebral microcirculatory responses to acute
      tobacco exposure in MSM.

PMID- 27037300
TI  - A Study on Stereoscopic X-ray Imaging Data Set on the Accuracy of Real-Time Tumor
      Tracking in External Beam Radiotherapy.
AB  - At external beam radiotherapy, stereoscopic X-ray imaging system is responsible
      as tumor motion information provider. This system takes X-ray images
      intermittently from tumor position (1) at pretreatment step to provide training
      data set for model construction and (2) during treatment to control the accuracy
      of correlation model performance. In this work, we investigated the effect of
      imaging data points provided by this system on treatment quality. Because some
      information is still lacking about (1) the number of imaging data points, (2)
      shooting time for capturing each data point, and also (3) additional imaging dose
      delivered by this system. These 3 issues were comprehensively assessed at (1)
      pretreatment step while training data set is gathered for prediction model
      construction and (2) during treatment while model is tested and reconstructed
      using new arrival data points. A group of real patients treated with CyberKnife
      Synchrony module was chosen in this work, and an adaptive neuro-fuzzy inference
      system was considered as consistent correlation model. Results show that a proper
      model can be constructed while the number of imaging data points is highly enough
      to represent a good pattern of breathing cycles. Moreover, a trade-off between
      the number of imaging data points and additional imaging dose is considered in
      this study. Since breathing phenomena are highly variable at different patients,
      the time for taking some of imaging data points is very important, while their
      absence at that critical time may yield wrong tumor tracking. In contrast, the
      sensitivity of another category of imaging data points is not high, while
      breathing is normal and in the control range. Therefore, an adaptive supervision
      on the implementation of stereoscopic X-ray imaging is proposed to intelligently
      accomplish shooting process, based on breathing motion variations.

PMID- 27037301
TI  - An Evaluation of Robotic and Conventional IMRT for Prostate Cancer: Potential for
      Dose Escalation.
AB  - This study compares conventional and robotic intensity modulated radiation
      therapy (IMRT) plans for prostate boost treatments and provides clinical insight
      into the strengths and weaknesses of each. The potential for dose escalation with
      robotic IMRT is further investigated using the "critical volume tolerance" method
      proposed by Roach et al. Three clinically acceptable treatment plans were
      generated for 10 prostate boost patients: (1) a robotic IMRT plan using fixed
      cones, (2) a robotic IMRT plan using the Iris variable aperture collimator, and
      (3) a conventional linac based IMRT (c-IMRT) plan. Target coverage, critical
      structure doses, homogeneity, conformity, dose fall-off, and treatment time, were
      compared across plans. The average bladder and rectum V75 was 17.1%, 20.0%, and
      21.4%, and 8.5%, 11.9%, and 14.1% for the Iris, fixed, and c-IMRT plans,
      respectively. On average the conformity index (nCI) was 1.20, 1.30, and 1.46 for
      the Iris, fixed, and c-IMRT plans. Differences between the Iris and the c-IMRT
      plans were statistically significant for the bladder V75 (P= .016), rectum V75
      (P= .0013), and average nCI (P =.002). Dose to normal tissue in terms of R50 was
      4.30, 5.87, and 8.37 for the Iris, fixed and c-IMRT plans, respectively, with
      statistically significant differences between the Iris and c-IMRT (P = .0013) and
      the fixed and c-IMRT (P = .001) plans. In general, the robotic IMRT plans
      generated using the Iris were significantly better compared to c-IMRT plans, and
      showed average dose gains of up to 34% for a critical rectal volume of 5%.

PMID- 27037302
TI  - Learning from incidents in healthcare: the journey, not the arrival, matters.

PMID- 27037303
TI  - Safety risks associated with the lack of integration and interfacing of hospital
      health information technologies: a qualitative study of hospital electronic
      prescribing systems in England.
AB  - BACKGROUND: Substantial sums of money are being invested worldwide in health
      information technology. Realising benefits and mitigating safety risks is however
      highly dependent on effective integration of information within systems and/or
      interfacing to allow information exchange across systems. As part of an English
      programme of research, we explored the social and technical challenges relating
      to integration and interfacing experienced by early adopter hospitals of
      standalone and hospital-wide multimodular integrated electronic prescribing
      (ePrescribing) systems. METHODS: We collected longitudinal qualitative data from
      six hospitals, which we conceptualised as case studies. We conducted 173
      interviews with users, implementers and software suppliers (at up to three
      different times), 24 observations of system use and strategic meetings, 17
      documents relating to implementation plans, and 2 whole-day expert round-table
      discussions. Data were thematically analysed initially within and then across
      cases, drawing on perspectives surrounding information infrastructures. RESULTS:
      We observed that integration and interfacing problems obstructed effective
      information transfer in both standalone and multimodular systems, resulting in
      threats to patient safety emerging from the lack of availability of timely
      information and duplicate data entry. Interfacing problems were immediately
      evident in some standalone systems where users had to cope with multiple log-ins,
      and this did not attenuate over time. Multimodular systems appeared at first
      sight to obviate such problems. However, with these systems, there was a
      perceived lack of data coherence across modules resulting in challenges in
      presenting a comprehensive overview of the patient record, this possibly
      resulting from the piecemeal implementation of modules with different
      functionalities. Although it was possible to access data from some primary care
      systems, we found poor two-way transfer of data between hospitals and primary
      care necessitating workarounds, which in turn led to the opportunity for new
      errors associated with duplicate and manual information transfer. Extending
      ePrescribing to include modules with other clinically important information
      needed to support care was still an aspiration in most sites, although some
      advanced multimodular systems had begun implementing this functionality.
      Multimodular systems were, however, seen as being difficult to interface with
      external systems. CONCLUSIONS: The decision to pursue a strategy of purchasing
      standalone systems and then interfacing these, or one of buying hospital-wide
      multimodular systems, is a pivotal one for hospitals in realising the vision of
      achieving a fully integrated digital record, and this should be predicated on a
      clear appreciation of the relative trade-offs between these choices. While
      multimodular systems offered somewhat better usability, standalone systems
      provided greater flexibility and opportunity for innovation, particularly in
      relation to interoperability with external systems and in relation to
      customisability to the needs of different user groups.

PMID- 27037305
TI  - Variable Lifting Index for Manual-Lifting Risk Assessment: A Preliminary
      Validation Study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of the new Variable
      Lifting Index (VLI) method, theoretically based on the Revised National Institute
      for Occupational Safety and Health [NIOSH] Lifting Equation (RNLE), in predicting
      the risk of acute low-back pain (LBP) in the past 12 months. BACKGROUND: A new
      risk variable termed the VLI for assessing variable manual lifting has been
      developed, but there has been no epidemiological study that evaluates the
      relationship between the VLI and LBP. METHOD: A sample of 3,402 study
      participants from 16 companies in different industrial sectors was analyzed. Of
      the participants, 2,374 were in the risk exposure group involving manual
      materials handling (MMH), and 1,028 were in the control group without MMH. The
      VLI was calculated for each participant in the exposure group using a systematic
      approach. LBP information was collected by occupational physicians at the study
      sites. The risk of acute LBP was estimated by calculating the odds ratio (OR)
      between levels of the risk exposure and the control group using a logistic
      regression analysis. Both crude and adjusted ORs for body mass index, gender, and
      age were analyzed. RESULTS: Both crude and adjusted ORs showed a dose-response
      relationship. As the levels of VLI increased, the risk of LBP increased. This
      risk relationship existed when VLI was greater than 1. CONCLUSION: The VLI method
      can be used to assess the risk of acute LBP, although further studies are needed
      to confirm the outcome and to define better VLI categories.

PMID- 27037304
TI  - Novel aspects of sialoglycan recognition by the Siglec-like domains of
      streptococcal SRR glycoproteins.
AB  - Serine-rich repeat glycoproteins are adhesins expressed by commensal and
      pathogenic Gram-positive bacteria. A subset of these adhesins, expressed by oral
      streptococci, binds sialylated glycans decorating human salivary mucin MG2/MUC7,
      and platelet glycoprotein GPIb. Specific sialoglycan targets were previously
      identified for the ligand-binding regions (BRs) of GspB and Hsa, two serine-rich
      repeat glycoproteins expressed by Streptococcus gordonii While GspB selectively
      binds sialyl-T antigen, Hsa displays broader specificity. Here we examine the
      binding properties of four additional BRs from Streptococcus sanguinis or
      Streptococcus mitis and characterize the molecular determinants of ligand
      selectivity and affinity. Each BR has two domains that are essential for
      sialoglycan binding by GspB. One domain is structurally similar to the glycan
      binding module of mammalian Siglecs (sialic acid-binding immunoglobulin-like
      lectins), including an arginine residue that is critical for glycan recognition,
      and that resides within a novel, conserved YTRY motif. Despite low sequence
      similarity to GspB, one of the BRs selectively binds sialyl-T antigen. Although
      the other three BRs are highly similar to Hsa, each displayed a unique ligand
      repertoire, including differential recognition of sialyl Lewis antigens and
      sulfated glycans. These differences in glycan selectivity were closely associated
      with differential binding to salivary and platelet glycoproteins. Specificity of
      sialoglycan adherence is likely an evolving trait that may influence the
      propensity of streptococci expressing Siglec-like adhesins to cause infective
      endocarditis.

PMID- 27037306
TI  - The ERS Research Agency: the beginning.
AB  - There is at the current time a significant opportunity for the ERS to leverage
      its experience and reputation as an international umbrella organisation to
      promote high-quality, multinational respiratory research with the goal of
      improving the health of respiratory patients. This editorial proposes a model for
      the role and structure of an ERS Research Agency. It is based upon research,
      implicit knowledge and explicit feedback from ERS members and selected external
      individuals and organisations.As with any new endeavour there are challenges and
      threats. Building a Research Agency will be a major undertaking that will require
      significant organisational planning, resources, effort and
      commitment.Organisations with multiple stakeholders tend to have a status quo
      inertia that has to be overcome for any significant new endeavour. The ERS
      Research Agency could be an investment in the future of respiratory research.

PMID- 27037307
TI  - A new perspective on COPD exacerbations: monitoring impact by measuring physical,
      psychological and social resilience.

PMID- 27037309
TI  - The lung microbiome: the perfect culprit for COPD exacerbations?

PMID- 27037310
TI  - Phenotyping bronchiectasis: is it all about sputum and infection?

PMID- 27037311
TI  - Mast cells in asthma: biomarker and therapeutic target.

PMID- 27037312
TI  - Asthma management in primary care: caring, sharing and working together.

PMID- 27037308
TI  - AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from
      concept to implementation.

PMID- 27037313
TI  - Deriving information from external Big Databases and Big Data analytics: all that
      glitters is not gold.

PMID- 27037314
TI  - The puzzle of metabolic effects of obstructive sleep apnoea in children.

PMID- 27037315
TI  - Have we found how to identify candidates for thrombolysis among normotensive
      patients with acute pulmonary embolism?

PMID- 27037316
TI  - Idiopathic pulmonary fibrosis: securing a confident diagnosis for every patient.

PMID- 27037317
TI  - Reducing antibiotics use for ventilator-associated pneumonia in brain-injured
      patients.

PMID- 27037318
TI  - Is there still room for therapeutic drug monitoring of linezolid in patients with
      tuberculosis?

PMID- 27037319
TI  - Is there still room for therapeutic drug monitoring of linezolid in patients with
      tuberculosis?

PMID- 27037320
TI  - Inclusion of children with airway disease for the development of spirometry
      reference data.

PMID- 27037321
TI  - Inclusion of children with airway disease for the development of spirometry
      reference data.

PMID- 27037322
TI  - Interstitial pneumonia with autoimmune features: the new consensus-based
      definition for this cohort of patients should be broadened.

PMID- 27037323
TI  - Interstitial pneumonia with autoimmune features: the new consensus-based
      definition for this cohort of patients should be broadened.

PMID- 27037324
TI  - "Lung cancer survival in Norway, 1997-2011: from nihilism to optimism." Yngvar
      Nilssen, Trond Eirik Strand, Lars Fjellbirkeland, Kristian Bartnes and Bjorn
      Moller. Eur Respir J 2016; 47: 275-287.

PMID- 27037327
TI  - Gut microbiota and protection from pneumococcal pneumonia.

PMID- 27037326
TI  - Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on
      early disease.
AB  - The European Society for Clinical and Economic Aspects of Osteoporosis,
      Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in
      rheumatoid arthritis (RA) and clinical trial methodology to comment on the new
      draft 'Guideline on clinical investigation of medicinal products for the
      treatment of RA' released by the European Medicines Agency (EMA). Special
      emphasis was placed by the group on the development of new drugs for the
      treatment of early RA. In the absence of a clear definition of early RA, it was
      suggested that clinical investigations in this condition were conducted in
      disease-modifying antirheumatic drugs naive patients with no more than 1 year
      disease duration. The expert group recommended using an appropriate improvement
      in disease activity (American College of Rheumatology (ACR) or
      Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low
      disease activity (by any score) as primary endpoints, with ACR/European League
      Against Rheumatism remission as a secondary endpoint. Finally, as compelling
      evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28)
      might not provide a reliable definition of remission, or sometimes even low
      disease activity, the group suggested replacing DAS28 as a measurement instrument
      to evaluate disease activity in RA clinical trials. Proposed alternatives
      included SDAI, CDAI and Boolean criteria.

PMID- 27037328
TI  - The natural history of acute Q fever: a prospective Australian cohort.
AB  - BACKGROUND: A detailed description of the natural history of acute Q fever,
      caused by infection with Coxiella burnetii, AIM: : To significantly increase
      understanding of the illness. DESIGN: Subjects with provisional acute Q fever (n
      = 115) were recruited from primary care in rural Australia, and followed
      prospectively by interview and blood collection including for serological
      confirmation. A nested series of subjects with prolonged illness (cases), and
      those without (controls), were investigated in detail. METHODS: Total phase I and
      phase II anti-C. burnetii antibodies were detected by complement fixation test;
      and IgG, IgM and IgA phase I and phase II titres by immunofluorescence. Flow
      cytometric analysis was conducted to enumerate circulating T cells subsets, B
      cells, monocytes and natural killer cells. RESULTS: Serological testing confirmed
      acute Q fever in 73 subjects (63%). The acute illness featured fever, headache,
      sweats, fatigue and anorexia; and varied widely in severity, causing an average
      of 8 days in bed and 15 days out of work or other role in the first month of
      illness. The illness course varied from 2 days to greater than a year. No cases
      of chronic, localized Q fever infection, such as endocarditis, were identified.
      Neither severe nor prolonged illness were associated with persistence of C.
      burnetii DNA, altered patterns of C. burnetii-specific IgG, IgM or IgA antibody
      production, or altered leucocyte subsets. CONCLUSIONS: The severity of acute Q
      fever alone predicted prolonged duration. Further studies are warranted to better
      understand the pathophysiology of prolonged illness after acute Q fever.

PMID- 27037329
TI  - A case of rheumatoid vasculitis.

PMID- 27037330
TI  - Alcohol drinking cultures of European adolescents.
AB  - BACKGROUND: Adolescent alcohol use varies across Europe. Differences in use might
      be due to variations in social drinking norms. These norms become apparent, e.g.
      in different proportions of alcohol drinking types per country. This study's
      purpose is to cluster European countries according to prevalence rates of alcohol
      drinking habits among adolescents aged 12-16. METHODS: Based on results of
      previously done cluster analyses regarding alcohol use patterns in Europe, a
      second level hierarchical cluster analysis is performed. To do so, the
      proportions of each drinking pattern per country (non, mild, episodic, frequent
      and heavy episodic use) across 25 European countries (N = 48 423, M = 13.83
      years, 48.5% male) are used as classifying variables. RESULTS: Three country
      clusters are extracted that differentiate between eight countries with 'mainly
      non-using' adolescents, six countries with adolescents who use alcohol in a
      'mainly mild but frequent' way and 11 countries that show the 'highest
      proportions of (heavy) episodic drinking adolescents'. CONCLUSIONS: When applying
      and developing intervention strategies, differences in adolescent alcohol
      drinking cultures (i.e. social drinking norms) within Europe should be focused
      on. Alcohol policies and prevention programs should take cultural aspects like
      social drinking norms into account.

PMID- 27037332
TI  - Psychological distress screener for risk of future mental sickness absence in non
      sicklisted employees.
AB  - BACKGROUND: Recently, a three-item screener, derived from the 16-item distress
      scale of the Four-Dimensional Symptom Checklist (4DSQ), was used to measure
      psychological distress in sicklisted employees. The aim of the present study was
      to investigate the ability of the 16-item distress scale and three-item distress
      screener to identify non-sicklisted employees at risk of sickness absence (SA)
      due to mental disorders. METHODS: Prospective cohort study including 4877
      employees working in distribution and transport. The 4DSQ distress scale was
      distributed at baseline in November 2010. SA diagnosed within the International
      Classification of Diseases -10 chapter F was defined as mental SA and retrieved
      from an occupational health register during 2-year follow-up. The area under the
      receiver operating characteristic curve (AUC) was used to discriminate between
      workers with ('cases') and without ('non-cases') mental SA during follow-up.
      RESULTS: A total of 2782 employees (57%) were included in complete cases
      analysis; 73 employees had mental SA during 2-year follow-up. Discrimination
      between cases and non-cases was similar for the 16-item distress scale (AUC =
      0.721; 95% CI, 0.622-0.823) and the three-item screener (AUC = 0.715; 95% CI,
      0.615-0.815). CONCLUSION: Healthcare providers could use the three-item distress
      screener to identify non-sicklisted employees at risk of future mental SA.

PMID- 27037331
TI  - Mid-career work patterns and physical and mental functioning at age 60-64:
      evidence from the 1946 British birth cohort.
AB  - BACKGROUND: Previous studies of the associations between unemployment and health
      have primarily focused on mental health and long-term associations have not often
      been explored. This study investigated if discontinuous employment in mid-career
      was related to self-reported physical and mental functioning at age 60-64 years.
      METHODS: Data come from the Medical Research Council National Survey of Health
      and Development, a British cohort that has been followed-up since birth in 1946.
      A total of 2061 study members had data available on mid-career employment
      patterns and physical and mental functioning assessed using the Short Form 36
      questionnaire at age 60-64. Employment patterns in mid-career were categorized
      into: (i) continuous employment; and discontinuous employment during; (ii) early
      period (ages 36-43); (iii) late period (ages 43-53); and 4) both periods.
      RESULTS: Continuous employment was reported by 63.3% of men and 38.7% of women,
      while 8.7% of men and 23.4% of women reported being in discontinuous employment
      during both early and late mid-career. When compared with those in continuous
      employment those in discontinuous employment during both early and late mid
      career had poorer physical functioning, men adjusted beta (difference in mean
      physical functioning T score) -3.84, 95% CI - 6.06 to - 1.63, P = 0.001 and women
      -3.62, 95% CI - 5.17 to - 2.08, P < 0.001. Findings were parallel but weaker for
      those in discontinuous employment during late mid-career. Discontinuous
      employment during both periods and particularly during late mid-career was
      associated with poorer mental functioning in early old age. CONCLUSIONS:
      Discontinuous employment during mid-career was associated with poorer self
      reported physical and mental functioning around the age of retirement.

PMID- 27037334
TI  - Maintaining Your Momentum: Moving Evidence Into Practice.

PMID- 27037335
TI  - Corrections.
AB  - In the December Ask the Experts article by Alexander and Zomp, "Best Practices:
      Full-Dose Delivery of Intravenous Medications via Infusion Pumps" (Crit Care
      Nurse. 2015;35(6):68-70), the authors would like to clarify that the Alaris pump
      referred to on page 70 is an older version and that the max rate is now the same
      for both primary and secondary settings on Alaris pumps (999 mL/h).

PMID- 27037336
TI  - Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With
      Sepsis.
AB  - Sepsis is associated with marked mortality, which may be reduced by prompt
      initiation of adequate, appropriate doses of antibiotic. Critically ill patients
      often have physiological changes that reduce blood and tissue concentrations of
      antibiotic and high rates of multidrug-resistant pathogens, which may affect
      patients' outcomes. All critical care professionals, including critical care
      nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to
      ensure sound antibiotic dosing and administration strategies for optimal
      microbial killing and patients' outcomes. Effective pathogen eradication occurs
      when the dose of antibiotic reaches or maintains optimal concentrations relative
      to the minimum inhibitory concentration for the pathogen. Time-dependent
      antibiotics, such as beta-lactams, can be given as extended or continuous
      infusions. Concentration-dependent antibiotics such as aminoglycosides are
      optimized by using high, once-daily dosing strategies with serum concentration
      monitoring. Vancomycin and fluoroquinolones are dependent on both time and
      concentration above the minimum inhibitory concentration. 

PMID- 27037337
TI  - Continuous Renal Replacement Therapy and Anticoagulation: What Are the Options?
AB  - Continuous renal replacement therapy is currently used as a standard treatment
      for acute kidney injury in the intensive care unit, particularly for patients
      with unstable hemodynamic status. Because this therapy is continuous, for days or
      weeks, and the extracorporeal blood circuit is large, the circuit is prone to
      clotting. Several methods of keeping the extracorporeal circuit patent are
      available, including heparin infusion, flushes with physiological saline, use of
      thrombin inhibitors, and citrate. This article reviews methods for continuous
      renal replacement therapy, anticoagulation, efficacy, and implications for
      bedside critical care. 

PMID- 27037338
TI  - beta-Blocker and Calcium Channel Blocker Poisoning: High-Dose Insulin/Glucose
      Therapy.
AB  - Overdoses of beta-blockers and calcium channel blockers can produce significant
      morbidity and mortality, and conventional therapies often do not work as
      treatments for these poisonings. High-dose insulin/glucose therapy has been
      successful in reversing the cardiotoxic effects of these drugs in cases where the
      standard therapies have failed, and it appears to be relatively safe. Many
      successes have been well documented, but the clinical experience consists of case
      reports, the mechanisms of action are not completely understood, and guidelines
      for use of the therapy are empirically derived and not standardized. Regardless
      of these limitations, high-dose insulin/glucose therapy can be effective, it is
      often recommended by clinical toxicologists and poison control centers, and
      critical care nurses should be familiar with when and how the therapy is used. 

PMID- 27037339
TI  - Use of a Vertical Expandable Prosthetic Titanium Rib in Children With Thoracic
      Insufficiency Syndrome and Scoliosis.
AB  - Thoracic insufficiency syndrome is the inability of the thorax to support normal
      respiration or lung growth. One treatment to address the thoracic deformities
      associated with the syndrome is placement of a vertical expandable prosthetic
      titanium rib. The goal is to restore thoracic volume, symmetry, and function and
      to allow for growth of the thorax in skeletally immature children. The main
      topics include indications for placement of a titanium rib, postoperative nursing
      care, potential complications, long-term follow-up, quality-of-life issues, and
      implications for critical care nurses and advanced practice nurses.

PMID- 27037340
TI  - Status Epilepticus in Adults: A Review of Diagnosis and Treatment.
AB  - Status epilepticus is a medical emergency that requires rapid diagnosis and
      treatment. Nonconvulsive status epilepticus is frequently underdiagnosed and
      therefore undertreated, which can lead to permanent neuronal damage resulting in
      disability or death. Despite the frequent occurrence and morbidity associated
      with status epilepticus, this topic has received little attention within the
      literature. A systematic approach to treatment should start with management of
      airway, breathing, and circulation, followed by administration of benzodiazepines
      and intravenous antiepileptic drugs, and rapid escalation of therapy to prevent
      morbidity and mortality. Armed with the information in this article, nurses will
      have a higher-level understanding of what to do when encountering a patient in
      status epilepticus. 

PMID- 27037341
TI  - We Do It for Our Patients.

PMID- 27037342
TI  - Best Method for Securing an Endotracheal Tube.

PMID- 27037343
TI  - Pulmonary Artery Catheters for Adult Patients in Intensive Care.

PMID- 27037344
TI  - The Impact of Family Engagement on Anxiety Levels in a Cardiothoracic Intensive
      Care Unit.

PMID- 27037346
TI  - I Am a Critical Care Nurse.

PMID- 27037347
TI  - Music as Medicine: The Therapeutic Potential of Music for Acute Stroke Patients.
AB  - Nurses caring for patients with acute stroke are likely to administer both music
      and medication with therapeutic intent. The administration of medication is based
      on accumulated scientific evidence and tailored to the needs of each patient.
      However, the therapeutic use of music is generally based on good intentions and
      anecdotal evidence. This review summarizes and examines the current literature
      regarding the effectiveness of music in the treatment of critically ill patients
      and the use of music in neurologically injured patients. The rationale for
      hypothesis-driven research to explore therapeutic music intervention in acute
      stroke is compelling. 

PMID- 27037348
TI  - Initial and Ongoing Verification of Feeding Tube Placement in Adults (applies to
      blind insertions and placements with an electromagnetic device).

PMID- 27037349
TI  - Reproductive coercion: an under-recognized challenge for primary care patients.
AB  - BACKGROUND: Reproductive coercion impacts many women of reproductive age.
      OBJECTIVES: We sought to explore how reproductive coercion, including pregnancy
      coercion and birth control sabotage, impacts women in a primary care population.
      METHODS: We administered a survey to women accessing care at a family medicine
      clinic in the Bronx, NY. Reproductive coercion was defined as a positive response
      to at least one of five questions adapted from previous studies. We assessed the
      association of reproductive and demographic characteristics with a lifetime
      history of reproductive coercion. RESULTS: At least one form of reproductive
      coercion was reported by 24% of the 97 respondents. Current lack of personal
      safety and a history of transactional sex for money or a place to stay were
      significantly associated with having experienced reproductive coercion (all P <=
      0.02). CONCLUSIONS: Reproductive coercion was common among women of reproductive
      age at this urban family medicine clinic in an underserved community, and was
      associated with other forms of control and violence. Clinicians are advised to
      discuss birth control sabotage and pregnancy coercion with their patients.

PMID- 27037350
TI  - Transgenerational epigenetic inheritance in mammals: how good is the evidence?
AB  - Epigenetics plays an important role in orchestrating key biologic processes.
      Epigenetic marks, including DNA methylation, histones, chromatin structure, and
      noncoding RNAs, are modified throughout life in response to environmental and
      behavioral influences. With each new generation, DNA methylation patterns are
      erased in gametes and reset after fertilization, probably to prevent these
      epigenetic marks from being transferred from parents to their offspring. However,
      some recent animal studies suggest an apparent resistance to complete erasure of
      epigenetic marks during early development, enabling transgenerational epigenetic
      inheritance. Whether there are similar mechanisms in humans remains unclear, with
      the exception of epigenetic imprinting. Nevertheless, a distinctly different
      mechanism-namely, intrauterine exposure to environmental stressors that may
      affect establishment of the newly composing epigenetic patterns after
      fertilization-is often confused with transgenerational epigenetic inheritance. In
      this review, we delineate the definition of and requirement for transgenerational
      epigenetic inheritance, differentiate it from the consequences of intrauterine
      exposure, and discuss the available evidence in both animal models and humans.
      Van Otterdijk, S. D., Michels, K. B. Transgenerational epigenetic inheritance in
      mammals: how good is the evidence?

PMID- 27037351
TI  - Value of ABNM Certification and MOC to Diplomates and the Public.

PMID- 27037352
TI  - In Memoriam: George E. Thoma, Jr., MD (1922-2016).

PMID- 27037353
TI  - George E. Thoma, Jr., MD: Launching JNM.

PMID- 27037354
TI  - SNMMI Leadership Update: Pathways to the Future of Nuclear Medicine.

PMID- 27037359
TI  - Substrate preference, uptake kinetics and bioenergetics in a facultatively
      autotrophic, thermoacidophilic crenarchaeote.
AB  - Facultative autotrophs are abundant components of communities inhabiting
      geothermal springs. However, the influence of uptake kinetics and energetics on
      preference for substrates is not well understood in this group of organisms.
      Here, we report the isolation of a facultatively autotrophic crenarchaeote,
      strain CP80, from Cinder Pool (CP, 88.7 degrees C, pH 4.0), Yellowstone National
      Park. The 16S rRNA gene sequence from CP80 is 98.8% identical to that from
      Thermoproteus uzonensis and is identical to the most abundant sequence identified
      in CP sediments. Strain CP80 reduces elemental sulfur (S8 degrees ) and
      demonstrates hydrogen (H2)-dependent autotrophic growth. H2-dependent autotrophic
      activity is suppressed by amendment with formate at a concentration in the range
      of 20-40 MUM, similar to the affinity constant determined for formate
      utilization. Synthesis of a cell during growth with low concentrations of formate
      required 0.5 MUJ compared to 2.5 MUJ during autotrophic growth with H2 These
      results, coupled to data indicating greater C assimilation efficiency when grown
      with formate as compared to carbon dioxide, are consistent with preferential use
      of formate for energetic reasons. Collectively, these results provide new
      insights into the kinetic and energetic factors that influence the physiology and
      ecology of facultative autotrophs in high-temperature acidic environments.

PMID- 27037360
TI  - Proteomic Analysis Reveals a Novel Mutator S (MutS) Partner Involved in Mismatch
      Repair Pathway.
AB  - The mismatch repair (MMR) family is a highly conserved group of proteins that
      function in correcting base-base and insertion-deletion mismatches generated
      during DNA replication. Disruption of this process results in characteristic
      microsatellite instability (MSI), repair defects, and susceptibility to cancer.
      However, a significant fraction of MSI-positive cancers express MMR genes at
      normal levels and do not carry detectable mutation in known MMR genes, suggesting
      that additional factors and/or mechanisms may exist to explain these MSI
      phenotypes in patients. To systematically investigate the MMR pathway, we
      conducted a proteomic analysis and identified MMR-associated protein complexes
      using tandem-affinity purification coupled with mass spectrometry (TAP-MS)
      method. The mass spectrometry data have been deposited to the ProteomeXchange
      with identifier PXD003014 and DOI 10.6019/PXD003014. We identified 230 high
      confidence candidate interaction proteins (HCIPs). We subsequently focused on
      MSH2, an essential component of the MMR pathway and uncovered a novel MSH2
      binding partner, WDHD1. We further demonstrated that WDHD1 forms a stable complex
      with MSH2 and MSH3 or MSH6,i.e.the MutS complexes. The specific MSH2/WDHD1
      interaction is mediated by the second lever domain of MSH2 and Ala(1123)site of
      WDHD1. Moreover, we showed that, just like MSH2-deficient cells, depletion of
      WDHD1 also led to 6-thioguanine (6-TG) resistance, indicating that WDHD1 likely
      contributes to the MMR pathway. Taken together, our study uncovers new components
      involved in the MMR pathway, which provides candidate genes that may be
      responsible for the development of MSI-positive cancers. 

PMID- 27037362
TI  - ERRATUM.

PMID- 27037363
TI  - Nut consumption, lipid profile, and health outcomes.

PMID- 27037361
TI  - Enhanced Purification of Ubiquitinated Proteins by Engineered Tandem Hybrid
      Ubiquitin-binding Domains (ThUBDs).
AB  - Ubiquitination is one of the most common post-translational modifications,
      regulating protein stability and function. However, the proteome-wide profiling
      of ubiquitinated proteins remains challenging due to their low abundance in
      cells. In this study, we systematically evaluated the affinity of ubiquitin
      binding domains (UBDs) to different types of ubiquitin chains. By selecting UBDs
      with high affinity and evaluating various UBD combinations with different lengths
      and types, we constructed two artificial tandem hybrid UBDs (ThUBDs), including
      four UBDs made of DSK2p-derived ubiquitin-associated (UBA) and ubiquilin 2
      derived UBA (ThUDQ2) and of DSK2p-derived UBA and RABGEF1-derived A20-ZnF
      (ThUDA20). ThUBD binds to ubiquitinated proteins, with markedly higher affinity
      than naturally occurring UBDs. Furthermore, it displays almost unbiased high
      affinity to all seven lysine-linked chains. Using ThUBD-based profiling with mass
      spectrometry, we identified 1092 and 7487 putative ubiquitinated proteins from
      yeast and mammalian cells, respectively, of which 362 and 1125 proteins had
      ubiquitin-modified sites. These results demonstrate that ThUBD is a refined and
      promising approach for enriching the ubiquitinated proteome while circumventing
      the need to overexpress tagged ubiquitin variants and use antibodies to recognize
      ubiquitin remnants, thus providing a readily accessible tool for the protein
      ubiquitination research community. 

PMID- 27037364
TI  - Reply to G-C Chen et al.

PMID- 27037365
TI  - Decrease in hunger and desire to eat: taste effect or the osmolar concentration?

PMID- 27037366
TI  - Reply to M Mehrdad.

PMID- 27037367
TI  - Erratum for Prado et al. A population-based approach to define body-composition
      phenotypes. Am J Clin Nutr 2014;99:1369-77.
AB  - Erratum for Prado et al. A population-based approach to define body-composition
      phenotypes. Am J Clin Nutr 2014;99:1369-77. Tables S7-S17 in the Online
      Supporting Material had incorrect numbers listed in them for the decile values of
      fat mass and appendicular skeletal muscle mass utilizing the LMS statistical
      procedure. Corrected tables have been provided.

PMID- 27037369
TI  - Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx
      degradation in hemorrhaged rats after different resuscitation fluids.
AB  - The endothelial glycocalyx plays an essential role in many physiological
      functions and is damaged after hemorrhage. Fluid resuscitation may further change
      the glycocalyx after an initial hemorrhage-induced degradation. Plasma levels of
      syndecan-1 and heparan sulfate have been used as indirect markers for glycocalyx
      degradation, but the extent to which these measures are representative of the
      events in the microcirculation is unknown. Using hemorrhage and a wide range of
      resuscitation fluids, we studied quantitatively the relationship between plasma
      biomarkers and changes in microvascular parameters, including glycocalyx
      thickness. Rats were bled 40% of total blood volume and resuscitated with seven
      different fluids (fresh whole blood, blood products, and crystalloids).
      Intravital microscopy was used to estimate glycocalyx thickness in >270
      postcapillary venules from 58 cremaster preparations in 9 animal groups; other
      microvascular parameters were measured using noninvasive techniques. Systemic
      physiological parameters and blood chemistry were simultaneously collected.
      Changes in glycocalyx thickness were negatively correlated with changes in plasma
      levels of syndecan-1 (r = -0.937) and heparan sulfate (r = -0.864). Changes in
      microvascular permeability were positively correlated with changes in both plasma
      biomarkers (r = 0.8, P < 0.05). Syndecan-1 and heparan sulfate were also
      positively correlated (r = 0.7, P < 0.05). Except for diameter and permeability,
      changes in local microcirculatory parameters (red blood cell velocity, blood
      flow, and wall shear rate) did not correlate with plasma biomarkers or glycocalyx
      thickness changes. This work provides a quantitative framework supporting plasma
      syndecan-1 and heparan sulfate as valuable clinical biomarkers of glycocalyx
      shedding that may be useful in guiding resuscitation strategies following
      hemorrhage.

PMID- 27037371
TI  - Plasticity of sarcolemmal KATP channel surface expression: relevance during
      ischemia and ischemic preconditioning.
AB  - Myocardial ischemia remains the primary cause of morbidity and mortality in the
      United States. Ischemic preconditioning (IPC) is a powerful form of endogenous
      protection against myocardial infarction. We studied alterations in KATP channels
      surface density as a potential mechanism of the protection of IPC. Using cardiac
      specific knockout of Kir6.2 subunits, we demonstrated an essential role for
      sarcolemmal KATP channels in the infarct-limiting effect of IPC in the mouse
      heart. With biochemical membrane fractionation, we demonstrated that sarcolemmal
      KATP channel subunits are distributed both to the sarcolemma and intracellular
      endosomal compartments. Global ischemia causes a loss of sarcolemmal KATP channel
      subunit distribution and internalization to endosomal compartments. Ischemia
      induced internalization of KATP channels was prevented by CaMKII inhibition. KATP
      channel subcellular redistribution was also observed with immunohistochemistry.
      Ischemic preconditioning before the index ischemia reduced not only the infarct
      size but also prevented KATP channel internalization. Furthermore, not only did
      adenosine mimic IPC by preventing infarct size, but it also prevented ischemia
      induced KATP channel internalization via a PKC-mediated pathway. We show that
      preventing endocytosis with dynasore reduced both KATP channel internalization
      and strongly mitigated infarct development. Our data demonstrate that plasticity
      of KATP channel surface expression must be considered as a potentially important
      mechanism of the protective effects of IPC and adenosine.

PMID- 27037370
TI  - Deletion of thioredoxin-interacting protein improves cardiac inotropic reserve in
      the streptozotocin-induced diabetic heart.
AB  - Although the precise pathogenesis of diabetic cardiac damage remains unclear,
      potential mechanisms include increased oxidative stress, autonomic nervous
      dysfunction, and altered cardiac metabolism. Thioredoxin-interacting protein
      (Txnip) was initially identified as an inhibitor of the antioxidant thioredoxin
      but is now recognized as a member of the arrestin superfamily of adaptor proteins
      that classically regulate G protein-coupled receptor signaling. Here we show that
      Txnip plays a key role in diabetic cardiomyopathy. High glucose levels induced
      Txnip expression in rat cardiomyocytes in vitro and in the myocardium of
      streptozotocin-induced diabetic mice in vivo. While hyperglycemia did not induce
      cardiac dysfunction at baseline, beta-adrenergic challenge revealed a blunted
      myocardial inotropic response in diabetic animals (24-wk-old male and female
      C57BL/6;129Sv mice). Interestingly, diabetic mice with cardiomyocyte-specific
      deletion of Txnip retained a greater cardiac response to beta-adrenergic
      stimulation than wild-type mice. This benefit in Txnip-knockout hearts was not
      related to the level of thioredoxin activity or oxidative stress. Unlike the beta
      arrestins, Txnip did not interact with beta-adrenergic receptors to desensitize
      downstream signaling. However, our proteomic and functional analyses demonstrated
      that Txnip inhibits glucose transport through direct binding to glucose
      transporter 1 (GLUT1). An ex vivo analysis of perfused hearts further
      demonstrated that the enhanced functional reserve afforded by deletion of Txnip
      was associated with myocardial glucose utilization during beta-adrenergic
      stimulation. These data provide novel evidence that hyperglycemia-induced Txnip
      is responsible for impaired cardiac inotropic reserve by direct regulation of
      insulin-independent glucose uptake through GLUT1 and plays a role in the
      development of diabetic cardiomyopathy.

PMID- 27037372
TI  - Open-loop (feed-forward) and feedback control of coronary blood flow during
      exercise, cardiac pacing, and pressure changes.
AB  - A control system model was developed to analyze data on in vivo coronary blood
      flow regulation and to probe how different mechanisms work together to control
      coronary flow from rest to exercise, and under a variety of experimental
      conditions, including cardiac pacing and with changes in coronary arterial
      pressure (autoregulation). In the model coronary flow is determined by the
      combined action of a feedback pathway signal that is determined by the level of
      plasma ATP in coronary venous blood, an adrenergic open-loop (feed-forward)
      signal that increases with exercise, and a contribution of pressure-mediated
      myogenic control. The model was identified based on data from exercise
      experiments where myocardial oxygen extraction, coronary flow, cardiac
      interstitial norepinephrine concentration, and arterial and coronary venous
      plasma ATP concentrations were measured during control and during adrenergic and
      purinergic receptor blockade conditions. The identified model was used to
      quantify the relative contributions of open-loop and feedback pathways and to
      illustrate the degree of redundancy in the control of coronary flow. The results
      indicate that the adrenergic open-loop control component is responsible for most
      of the increase in coronary blood flow that occurs during high levels of
      exercise. However, the adenine nucleotide-mediated metabolic feedback control
      component is essential. The model was evaluated by predicting coronary flow in
      cardiac pacing and autoregulation experiments with reasonable fits to the data.
      The analysis shows that a model in which coronary venous plasma adenine
      nucleotides are a signal in local metabolic feedback control of coronary flow is
      consistent with the available data.

PMID- 27037373
TI  - Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in
      coronary artery soluble guanylate cyclase depletion by angiotensin II.
AB  - Oxidation of the soluble guanylate cyclase (sGC) heme promotes loss of regulation
      by nitric oxide (NO) and depletion of sGC. We hypothesized that angiotensin II
      (ANG II) stimulation of mitochondrial superoxide by its type 1 receptor could
      function as a potential inhibitor of heme biosynthesis by ferrochelatase, and
      this could decrease vascular responsiveness to NO by depleting sGC. These
      processes were investigated in a 24-h organoid culture model of bovine coronary
      arteries (BCA) with 0.1 MUM ANG II. Treatment of BCA with ANG II increased
      mitochondrial superoxide, depleted mitochondrial superoxide dismutase (SOD2),
      ferrochelatase, and cytochrome oxidase subunit 4, and sGC, associated with
      impairment of relaxation to NO. These processes were attenuated by organoid
      culture with 8-bromo-cGMP and/or delta-aminolevulinic acid (a stimulator of sGC
      by protoporphyrin IX generation and heme biosynthesis). Organoid culture with
      Mito-TEMPOL, a scavenger of mitochondrial matrix superoxide, also attenuated ANG
      II-elicited ferrochelatase depletion and loss of relaxation to NO, whereas
      organoid culture with Tempol, an extramitochondrial scavenger of superoxide,
      attenuated the loss of relaxation to NO by ANG II, but not ferrochelatase
      depletion, suggesting cytosolic superoxide could be an initiating factor in the
      loss of sGC regulation by NO. The depletion of cytochrome oxidase subunit 4 and
      sGC (but not catalase) suggests that sGC expression may be very sensitive to
      depletion of heme caused by ANG II disrupting ferrochelatase activity by
      increasing mitochondrial superoxide. In addition, cGMP-dependent activation of
      protein kinase G appears to attenuate these ANG II-stimulated processes through
      both preventing SOD2 depletion and increases in mitochondrial and
      extramitochondrial superoxide.

PMID- 27037374
TI  - What should we do about alcohol?

PMID- 27037375
TI  - Brexit and health services.

PMID- 27037376
TI  - Appropriateness of unscheduled hospital admissions from care homes.
AB  - Unscheduled hospital admissions from care homes are common and potentially
      avoidable but little guidance is available as to what constitutes an appropriate
      hospital admission. We surveyed healthcare professionals' opinions on a range of
      common scenarios affecting care-home residents. We developed seven clinical
      vignettes and an accompanying questionnaire. We used purposive sampling to obtain
      opinions from relevant primary care and secondary care teams. We asked assessors
      to comment on whether they would favour hospital admission and to justify their
      response using pre-selected options and/or free text. Admission to hospital was
      judged inappropriate in 54.6% of responses. Opinion on admission varied according
      to the case, with fewer than half of respondents agreeing for three of the seven
      cases. Recurring themes were uncertainty around services available to care homes
      and anticipatory care planning. The lack of consensus suggests that concepts
      surrounding inappropriate care-home admission are not shared by staff who provide
      care for this patient group. 

PMID- 27037377
TI  - Cost effectiveness of inpatient rehabilitation in patients with brain injury.
AB  - Rehabilitation following acquired brain injury improves health outcomes, reduces
      disability, and improves quality of life. We assessed the cost effectiveness of
      inpatient rehabilitation after brain injury in individuals with brain injury
      admitted to the Irish national tertiary specialist rehabilitation centre in 2011.
      Patients' score on the Disability Rating Scale (DRS) was recorded on admission
      and at discharge after intensive inpatient rehabilitation. Cost savings
      attributed to the rehabilitation programme were calculated as the difference
      between direct care costs on admission and discharge. Direct costs of care were
      calculated as the weekly cost of the care-assistant hours required to care for
      patients on the basis of their level of disability or daily nursing-home bed cost
      when this was required. Of 63 patients, complete DRS information for admission
      and discharge was available for 41. DRS scores, and therefore average levels of
      functioning, differed significantly at admission (2.3, between mildly and
      moderately dependent) and discharge (1.1, independent in special environments,
      p<0.01). Average weekly care costs fell from ?629 to ?242, with costs recouped
      within 30 months. Thus, substantial savings result from inpatient rehabilitation,
      and these savings could have been greater had we considered also the economic
      benefit of enabling patients to return to employment. 

PMID- 27037378
TI  - The Bromhead Care Home Service: the impact of a service for care home residents
      with dementia on hospital admission and dying in preferred place of care.
AB  - People with dementia have worse outcomes associated with hospital admission, are
      more likely to have interventions and are less likely to be offered palliative
      care than people without dementia. Advance care planning for care home residents
      has been shown to reduce hospital admissions without increasing mortality.
      Studies have shown that staff confidence in managing delirium, a common reason
      for admission, improves with training. A service combining education for care
      home staff and advance care planning for care home residents with dementia was
      introduced to care homes in Boston, UK. There were improvements in staff
      confidence in recognition, prevention, management and knowledge of factors
      associated with delirium and dysphagia. 92% of carers rated the service >9/10.
      Admissions fell by 37% from baseline in the first year and 55% in the second and
      third years. All but one resident died in the preferred place of care. 

PMID- 27037379
TI  - Deprivation influences the emergency admission rate of ambulatory care sensitive
      conditions.
AB  - Ambulatory care sensitive conditions (ACSCs) are a group of conditions judged to
      be suitable for healthcare efficiency initiatives to reduce the rate of hospital
      admissions. All emergency medical admissions to an Irish hospital between 2002
      and 2013 were assessed for ACSCs. They were categorised by quintile of
      deprivation index and evaluated against hospital admission rate. Univariable and
      multivariable risk estimates were calculated, using logistic regression or zero
      truncated Poisson regression. There were 66,861 admissions in 36,214 patients.
      ACSCs represented 66.4% of admissions. The rate of ACSC admissions increased with
      deprivation index, Q1 10.4 (95% confidence interval (CI) 10.2-10.5), Q2 17.3 (95%
      CI 17.2-17.5), Q3 34.0 (95% CI 33.7-34.2), Q4 30.2 (95% CI 30.0-30.4) and Q5 44.5
      (95% CI 43.8- 45.1) (p<0.001), corresponding incidence rate ratios compared with
      Q1 were: Q2 1.67 (95% CI 1.64-1.70), Q3 3.28 (95% CI 3.22-3.33), Q4 2.92 (95% CI
      2.87-2.97) and Q5 4.29 (95% CI 4.20-4.39) (p<0.001). ACSCs are common in acute
      medical admissions and are strongly influenced by the underlying social
      demographics of the population. 

PMID- 27037380
TI  - Putting an end to Black Wednesday: improving patient safety by achieving
      comprehensive trust induction and mandatory training by day 1.
AB  - The term 'Black Wednesday' has been used to describe the August national
      changeover day, a day when a new cohort of inexperienced doctors start work, many
      of whom are absent from patient care to attend organisational induction and
      mandatory training. In this paper, we report on the development and
      implementation of a novel, interactive e-learning programme for induction and
      mandatory training for junior doctors in a district general hospital in south
      west England from August 2013. This comprehensive mandatory-training programme
      with summative assessment saved 19.5 hours of trust time per trainee. Since the
      programme's inception, the completion rate has been 100% (n = 370). Subgroup
      analysis of starters from August 2013 (n = 141) showed that 85.7% completed by
      day 1 (mean time of completion 3.0 days before day 1, standard deviation 14.2
      days). Importantly, 90 minutes of induction was freed on Black Wednesday,
      enabling earlier, ward-based clinical orientation, thereby enhancing patient
      safety. We believe that this is the first programme to combine induction with
      fully assessed, comprehensive mandatory training in a single package. Such an
      approach is suitable for widespread application and is to be implemented
      regionally. 

PMID- 27037382
TI  - Who should be referred to a specialist pulmonary -hypertension centre - a
      referrer's guide.
AB  - The introduction of pulmonary hypertension (PH)-specific drugs has allowed
      certain forms of PH to become more treatable. However, patients with these
      diseases can present to a number of medical specialties and can be challenging to
      identify, particularly in a non-specialist setting. This article provides
      guidance on who should be investigated and referred on to a specialist centre,
      highlighting the potential pitfalls during assessment. 

PMID- 27037383
TI  - Writing clinical scenarios for clinical science questions.
AB  - Written knowledge assessments for physicians in training typically involve
      multiple-choice questions that use a clinical scenario in a single-best-answer
      format. The Royal College of Physicians Part 1 MRCP(UK) examination includes
      basic sciences themes that are challenging to assess through a clinical scenario.
      A realistic clinical setting based on everyday clinical practice and integral to
      the question is the clearest demonstration that the knowledge being assessed is
      clinically relevant. However, without special attention to detail, the scenario
      in a clinical science question can appear redundant or artificial. Reading
      unnecessary material frustrates candidates and threatens the reputation of the
      assessment. In this paper we discuss why a clinical scenario is important for
      basic science questions and offer advice on setting realistic and plausible
      clinical scenarios for such questions. 

PMID- 27037381
TI  - Viral arthritis.
AB  - Acute-onset arthritis is a common clinical problem facing both the general
      clinician and the rheumatologist. A viral aetiology is though to be responsible
      for approximately 1% of all cases of acute arthritis with a wide range of causal
      agents recognised. The epidemiology of acute viral arthritis continues to evolve,
      with some aetiologies, such as rubella, becoming less common due to vaccination,
      while some vector-borne viruses have become more widespread. A travel history
      therefore forms an important part of the assessment of patients presenting with
      an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the
      alphaviruses are among the most important causes of virally mediated arthritis.
      Targeted serological testing may be of value in establishing a diagnosis, and
      clinicians must also be aware that low-titre autoantibodies, such as rheumatoid
      factor and antinuclear antibody, can occur in the context of acute viral
      arthritis. A careful consideration of epidemiological, clinical and serological
      features is therefore required to guide clinicians in making diagnostic and
      treatment decisions. While most virally mediated arthritides are self-limiting
      some warrant the initiation of specific antiviral therapy. 

PMID- 27037384
TI  - What does quality healthcare look like to adolescents and young adults? Ask the
      experts!
AB  - It is widely recognised that developmentally appropriate services for adolescents
      and young people improve both healthcare experience and health outcomes. However,
      there is limited evidence of using young people's expertise to evaluate services,
      or of young people participating in service developments or design to meet their
      healthcare needs. This report covers both the process and outcomes of a
      collaborative project with a group of young people (aged 17-25 years) who are
      'experts by experience'. We used qualitative mixed methodology to derive themes
      from narrative accounts of these young people's healthcare experiences to develop
      an assessment framework that they identified as being relevant to evaluating
      services. Informing young people about other assessment measures currently in use
      (including the Department of Health's You're Welcome quality criteria) enabled
      the group to further develop their views and refine their proposed assessment
      framework. This paper is co-authored with young people, enabling them to directly
      voice their views about healthcare services. Reflections on this process and
      recommendations for working more collaboratively with young people to evaluate
      healthcare services are also given. 

PMID- 27037385
TI  - Antiplatelet therapy - a summary for the general physicians.
AB  - Platelets play a very important role in physiological haemostasis and thrombus
      formation. Platelet aggregation is the key pathophysiological factor in the
      development of arterial ischaemic events, including coronary artery disease,
      cerebrovascular accidents and peripheral arterial disease. As such, antiplatelet
      therapy plays a very important role in preventing recurrent events in the
      individuals who are affected by one of these conditions. Until recently, the
      repertoire of antiplatelet therapy was limited to aspirin and clopidogrel.
      However, this landscape has changed dramatically with the advent of newer and
      more potent agents, prasugrel and ticagrelor and also the glycoprotein IIb/IIIa
      antagonists. This armamentarium is likely to expand further with the advent of
      protease-activated receptor-1 antagonists and the intravenous cangrelor. This
      review summarises the different agents available and some practical
      considerations for their use from a general physician's perspective. 

PMID- 27037386
TI  - Safe sedation for the non-anaesthetist.
AB  - Sedation has become an essential part of many invasive medical procedures.
      However, over the years, there have been concerns about the safety of sedation
      techniques. Various combinations of drug-based and non-drug-based approaches are
      used for procedural sedation depending on patient factors and the anticipated
      discomfort associated with each procedure. The common denominator for successful
      practice for a sedationist is knowledge, adequate training and a mechanism for
      revalidation. 

PMID- 27037387
TI  - Harveian Oration 2015: Medicine, science and values - with hindsight and
      foresight.

PMID- 27037388
TI  - Vitamin D - what is normal according to latest research and how should we deal
      with it?
AB  - Vitamin D deficiency is a public health concern. Mediated by classical endocrine
      effects, vitamin D deficiency is causally linked with bone and calcium disorders.
      Non-endocrine actions of vitamin D are also widely recognised and these effects
      are mediated by local tissue activation of vitamin D bringing about intracrine
      effects in non-classical sites. Supported by large volumes of observational
      studies linking low circulating vitamin D with negative outcomes for many common
      disease states, there is growing interest that vitamin D may be central to the
      pathology and outcomes of many common diseases, including cardiovascular, cancer
      and autoimmune conditions. This article explores the quality of evidence linking
      vitamin D and various disease outcomes, and furthermore describes some of the
      cellular and molecular mechanisms of vitamin D action that may help explain some
      of the incongruity of data observed in observational versus interventional
      studies of vitamin D supplementation. 

PMID- 27037389
TI  - HIV-indicator-condition-driven HIV testing: clinically effective but still rarely
      implemented.
AB  - In the UK, outcomes for people living with HIV are excellent. However, a quarter
      of those living with HIV do not know their status, and almost half are diagnosed
      late. Strategies to broaden HIV testing are needed. HIV indicator conditions are
      those thought to be associated with HIV infection because they share risk factors
      (eg viral hepatitis) or because they arise as a result of early or late
      immunodeficiency (eg bacterial pneumonia, Kaposi's sarcoma). They comprise all
      AIDS-defining conditions, but also many non-AIDS-defining conditions spanning the
      spectrum of medicine. Patients presenting with indicator conditions should
      routinely be offered an HIV test. This approach is likely to be clinically
      effective, because knowledge of HIV status is essential in the management of many
      conditions. It is cost effective if the prevalence of HIV infection is greater
      than 0.1%. The strategy removes the need for risk assessment, and is acceptable
      to patients and healthcare practitioners. If broadly implemented, it is likely to
      be effective at a public health level, and will help to reduce both undiagnosed
      HIV and late diagnoses of HIV. Here we review the emerging evidence base that
      supports the value of routine HIV testing in indicator conditions. 

PMID- 27037390
TI  - Primary HIV infection: a medical and public health emergency requiring rapid
      specialist management.
AB  - Primary HIV infection (PHI) refers to the first six months following HIV
      acquisition and represents a unique opportunity for expedited diagnosis, and
      consideration of rapid antiretroviral therapy (ART) initiation to improve immune
      function, reduce the size of the viral reservoir and limit the risk of onward
      viral transmission. Failure to diagnose and rapidly treat individuals with PHI
      has significant individual and public health implications. The Strategic Timing
      of AntiRetroviral Treatment trial recently identified a clinical benefit of
      immediate ART over deferral of treatment according to CD4 count threshold, and
      has led to rapid changes in World Health Organization and specialist national
      guidelines. For all individuals living with HIV, the offer of immediate therapy
      irrespective of CD4 count is now recommended. This paper summarises the
      presentation and management of PHI, incorporating current research and guideline
      changes and discusses the role of PHI in onward transmission. 

PMID- 27037391
TI  - Syphilis: presentations in general medicine.
AB  - Syphilis is caused by the spirochete bacteriumTreponema pallidumand can be
      transmitted both sexually and from mother to child.T pallidumcan infect any organ
      and produces a clinical disease with a relapsing and remitting course. It is not
      hard to see, therefore, why it is often described as the great mimic. In this
      review, we provide an update of modern syphilis epidemiology, clinical
      presentations, and testing and treatment strategies. 

PMID- 27037392
TI  - Hepatitis C and sex.
AB  - An outbreak of acute hepatitis C among HIV-positive men who have sex with men
      (MSM) in the last decade has been shown to be sexually transmitted. Initially
      recreational drug use, in particular drug injection, was not prevalent among
      those becoming infected with hepatitis C. However more recently chemsex (the use
      of drugs to enhance sexual experience) and its associated drugs, which are not
      uncommonly injected, have become more frequently reported among those diagnosed
      with hepatitis C. It is hoped that the widespread -introduction of direct-acting
      antivirals and upscaling of numbers treated may have a positive impact on this
      epidemic. However their introduction may negatively impact on the perceived risk
      of acquiring hepatitis C and in conjunction with the introduction of HIV
      transmission prevention strategies may result in increased transmissions and
      spread to the HIV-negative MSM population. 

PMID- 27037393
TI  - Sexually acquired reactive arthritis.
AB  - Sexually acquired reactive arthritis (SARA) may present acutely to general
      physicians. It is important to consider the condition and to identify key
      features in the history and examination so that appropriate investigations are
      taken and optimum treatment is given. Involvement of relevant specialists in the
      management is essential and where sexually transmitted infections are identified,
      partner notification is required. 

PMID- 27037395
TI  - Lesson of the month 1: Splinter haemorrhages as a pointer to gastrointestinal
      malignancy.
AB  - A 58-year-old man was referred for review due to the finding of splinter
      haemorrhages and digital infarcts. Further questioning revealed a history of
      unintentional weight loss and calf pain. There were no other clinical features of
      endocarditis, and no clear cause for the splinter haemorrhages on initial
      investigations. The discovery of widespread thromboembolic disease prompted a
      search for malignancy and an eventual diagnosis of oesophageal adenocarcinoma.
      Splinter haemorrhages resolved with anticoagulation and directed treatment of the
      underlying malignancy. This case report reminds clinicians of the potentially
      broad differential diagnosis associated with this clinical sign. 

PMID- 27037396
TI  - Lesson of the month 2: Catecholamine-induced cardiomyopathy - pitfalls in
      diagnosis and medical management.
AB  - Cardiomyopathy as the initial presentation of phaeochromocytoma (PCA) is
      uncommon. Diagnostic work-up and perioperative management may be challenging
      within this context. We report three cases of PCA presenting with cardiomyopathy
      to illustrate the pitfalls in diagnosis and management. None of the patients had
      typical adrenergic symptoms and all three were established on beta-blockers prior
      to diagnosis. Their fractionated plasma catecholamine levels were elevated and
      the diagnosis of PCA was confirmed with various imaging modalities and post
      adrenalectomy. Interpretation of fractionated catecholamine levels in the context
      of established cardiomyopathy is difficult as cardiac failure of any aetiology
      generates an adrenergic response. Hence screening all patients with idiopathic
      cardiomyopathy is likely to generate a high false-positive rate. However, a high
      index of suspicion should prompt further diagnostic work-up in patients with
      idiopathic cardiomyopathy for occult PCAs. Peer-reviewed guidelines are required
      to guide the investigation and management of suspected catecholamine-induced
      cardiomyopathy. 

PMID- 27037397
TI  - Don't neglect the sinus!

PMID- 27037399
TI  - Hereditary angioedema with F12 mutation: first report of three cases associated
      with immune disorders.

PMID- 27037400
TI  - Non-uraemic calciphylaxis - an unexpected differential diagnosis for a necrotic
      ulcer.

PMID- 27037401
TI  - Response.

PMID- 27037402
TI  - Sticks and stones: investigating rude, dismissive and aggressive communication
      between doctors.

PMID- 27037403
TI  - Response.

PMID- 27037404
TI  - The Royal College of Physicians' Fallsafe care bundles applied trustwide: the
      Northumbria experience 2013.

PMID- 27037405
TI  - Erratum: Emergence of Magnusiomyces capitatus infections in Western Nepal.
AB  - In "Emergence of Magnusiomyces capitatus infections in Western Nepal" by Hosuru
      Subramanya Supram et al. [Med Mycol 2016; 54: 103-110], several of the references
      were incorrectly listed. The corrected references are listed below. The authors
      regret these errors.

PMID- 27037406
TI  - High resolution structures of the human ABO(H) blood group enzymes in complex
      with donor analogs reveal that the enzymes utilize multiple donor conformations
      to bind substrates in a stepwise manner.

PMID- 27037407
TI  - The Emerging Issue of 25-Hydroxyvitamin D in Foods.

PMID- 27037411
TI  - Nanofluidic Digital PCR and Extended Genotyping of RAS and BRAF for Improved
      Selection of Metastatic Colorectal Cancer Patients for Anti-EGFR Therapies.
AB  - The clinical significance of low-frequent RAS pathway-mutated alleles and the
      optimal sensitivity cutoff value in the prediction of response to anti-EGFR
      therapy in metastatic colorectal cancer (mCRC) patients remains controversial. We
      aimed to evaluate the added value of genotyping an extended RAS panel using a
      robust nanofluidic digital PCR (dPCR) approach. A panel of 34 hotspots, including
      RAS (KRAS and NRAS exons 2/3/4) and BRAF (V600E), was analyzed in tumor FFPE
      samples from 102 mCRC patients treated with anti-EGFR therapy. dPCR was compared
      with conventional quantitative PCR (qPCR). Response rates, progression-free
      survival (PFS), and overall survival (OS) were correlated to the mutational
      status and the mutated allele fraction. Tumor response evaluations were not
      available in 9 patients and were excluded for response rate analysis. Twenty-two
      percent of patients were positive for one mutation with qPCR (mutated alleles
      ranged from 2.1% to 66.6%). Analysis by dPCR increased the number of positive
      patients to 47%. Mutated alleles for patients only detected by dPCR ranged from
      0.04% to 10.8%. An inverse correlation between the fraction of mutated alleles
      and radiologic response was observed. ROC analysis showed that a fraction of 1%
      or higher of any mutated alleles offered the best predictive value for all
      combinations of RAS and BRAF analysis. In addition, this threshold also optimized
      prediction both PFS and OS. We conclude that mutation testing using an extended
      gene panel, including RAS and BRAF with a threshold of 1% improved prediction of
      response to anti-EGFR therapy. Mol Cancer Ther; 15(5); 1106-12. (c)2016 AACR.

PMID- 27037413
TI  - The inner workings of stress fibers - from contractile machinery to focal
      adhesions and back.
AB  - Ventral stress fibers and focal adhesions are physically coupled structures that
      play key roles in cellular mechanics and force sensing. The tight functional
      interdependence between the two is manifested not only by their apparent
      proximity but also by the fact that ventral stress fibers and focal adhesions are
      simultaneously diminished upon actomyosin relaxation, and grow when subjected to
      external stretching. However, whereas the apparent co-regulation of the two
      structures is well-documented, the underlying mechanisms remains poorly
      understood. In this Commentary, we discuss some of the fundamental, yet still
      open questions regarding ventral stress fiber structure, its force-dependent
      assembly, as well as its capacity to generate force. We also challenge the common
      approach - i.e. ventral stress fibers are variants of the well-studied striated
      or smooth muscle machinery - by presenting and critically discussing alternative
      venues. By highlighting some of the less-explored aspects of the interplay
      between stress fibers and focal adhesions, we hope that this Commentary will
      encourage further investigation in this field. 

PMID- 27037412
TI  - RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent,
      Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis.
AB  - Dysregulated cellular apoptosis and resistance to cell death are hallmarks of
      neoplastic initiation and disease progression. Therefore, the development of
      agents that overcome apoptosis dysregulation in tumor cells is an attractive
      therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly
      dependent on death receptor (DR) hyperclustering on the cell surface. However,
      strategies to activate DR5 or DR4 through agonistic antibodies have had only
      limited clinical success. To pursue an alternative approach for tumor-targeted
      induction of apoptosis, we engineered a bispecific antibody (BsAb), which
      simultaneously targets fibroblast-activation protein (FAP) on cancer-associated
      fibroblasts in tumor stroma and DR5 on tumor cells. We hypothesized that bivalent
      binding to both FAP and DR5 leads to avidity-driven hyperclustering of DR5 and
      subsequently strong induction of apoptosis in tumor cells but not in normal
      cells. Here, we show that RG7386, an optimized FAP-DR5 BsAb, triggers potent
      tumor cell apoptosis in vitro and in vivo in preclinical tumor models with FAP
      positive stroma. RG7386 antitumor efficacy was strictly FAP dependent, was
      independent of FcR cross-linking, and was superior to conventional DR5
      antibodies. In combination with irinotecan or doxorubicin, FAP-DR5 treatment
      resulted in substantial tumor regression in patient-derived xenograft models. FAP
      DR5 also demonstrated single-agent activity against FAP-expressing malignant
      cells, due to cross-binding of FAP and DR5 across tumor cells. Taken together,
      these data demonstrate that RG7386, a novel and potent antitumor agent in both
      mono- and combination therapies, overcomes limitations of previous DR5 antibodies
      and represents a promising approach to conquer tumor-associated resistance to
      apoptosis. Mol Cancer Ther; 15(5); 946-57. (c)2016 AACR.

PMID- 27037414
TI  - Signals and Receptors.
AB  - Communication between cells in a multicellular organism occurs by the production
      of ligands (proteins, peptides, fatty acids, steroids, gases, and other low
      molecular-weight compounds) that are either secreted by cells or presented on
      their surface, and act on receptors on, or in, other target cells. Such signals
      control cell growth, migration, survival, and differentiation. Signaling
      receptors can be single-span plasma membrane receptors associated with tyrosine
      or serine/threonine kinase activities, proteins with seven transmembrane domains,
      or intracellular receptors. Ligand-activated receptors convey signals into the
      cell by activating signaling pathways that ultimately affect cytosolic
      machineries or nuclear transcriptional programs or by directly translocating to
      the nucleus to regulate transcription.

PMID- 27037416
TI  - The Role of Functional Prion-Like Proteins in the Persistence of Memory.
AB  - Prions are a self-templating amyloidogenic state of normal cellular proteins,
      such as prion protein (PrP). They have been identified as the pathogenic agents,
      contributing to a number of diseases of the nervous system. However, the
      discovery that the neuronal RNA-binding protein, cytoplasmic polyadenylation
      element-binding protein (CPEB), has a prion-like state that is involved in the
      stabilization of memory raised the possibility that prion-like proteins can serve
      normal physiological functions in the nervous system. Here, we review recent
      experimental evidence of prion-like properties of neuronal CPEB in various
      organisms and propose a model of how the prion-like state may stabilize memory. 

PMID- 27037417
TI  - Adolescents' Spirituality and Cystic Fibrosis Airway Clearance Treatment
      Adherence: Examining Mediators.
AB  - OBJECTIVE: Adolescent cystic fibrosis (CF) treatment adherence is a significant
      multidimensional issue. Using the Theory of Reasoned Action (TRA), this study
      examined the role of spiritual factors in adherence. METHODS: Forty-five 11-19
      year-olds diagnosed with CF completed questionnaires concerning psychosocial,
      spiritual, and adherence-related constructs and Daily Phone Diaries to calculate
      treatment adherence. Exploratory Factor Analysis identified two spiritual factors
      used in subsequent analyses. The mediating roles of attitude toward the
      treatment's value (utility), subjective behavioral norms (the product of
      perceived behavioral norms and one's motivation to comply with them), self
      efficacy for completing the treatments and treatment intentions in the
      relationship between spiritual factors and treatment adherence were tested with
      path analysis. RESULTS: Lower 'spiritual struggle' and greater 'engaged
      spirituality' predicted treatment attitude (utility) and subjective behavioral
      norms, which, together with self-efficacy, predicted treatment intentions.
      Finally, treatment intentions predicted airway clearance adherence. CONCLUSIONS:
      Findings were consistent with the TRA. Engaged spirituality supports pro
      adherence determinants and behavior. Spiritual struggle's negative associations
      with outcomes warrant screening and intervention.

PMID- 27037418
TI  - The double-edged sword of the mammalian oocyte--advantages, drawbacks and
      approaches for basic and clinical analysis at the single cell level.

PMID- 27037415
TI  - Histone Modifications and Cancer.
AB  - Histone posttranslational modifications represent a versatile set of epigenetic
      marks involved not only in dynamic cellular processes, such as transcription and
      DNA repair, but also in the stable maintenance of repressive chromatin. In this
      article, we review many of the key and newly identified histone modifications
      known to be deregulated in cancer and how this impacts function. The latter part
      of the article addresses the challenges and current status of the epigenetic drug
      development process as it applies to cancer therapeutics.

PMID- 27037419
TI  - Autophagy and p53.
AB  - Macroautophagy (autophagy hereafter) captures, degrades, and recycles
      intracellular components to maintain metabolic homeostasis and protein and
      organelle quality control. Autophagy thereby promotes survival in starvation and
      prevents tissue degeneration. There is an important relationship between
      autophagy and p53. Autophagy suppresses p53 and also p53 activates autophagy. The
      suppression of p53 by autophagy is important for tumor promotion and likely also
      for preventing tissue degeneration. Alternatively, the activation of autophagy by
      p53 suggests that autophagy is part of the protective function of p53. Uncovering
      the underlying mechanisms of the autophagy-p53 reciprocal functional interaction
      and has important implications for human disease and treatment. 

PMID- 27037420
TI  - Genetic Modifiers of the p53 Pathway.
AB  - The tumor suppressor gene TP53 is the most frequently mutated gene in human
      cancer; this gene is subject to inactivation by mutation or deletion in >50% of
      sporadic cancers. Genes that encode proteins that regulate p53 function, such as
      MDM2, MDM4, and CDKN2A (p14(ARF)) are also frequently altered in tumors, and it
      is generally believed that the p53 pathway is likely to be inactivated by
      mutation in close to 100% of human tumors. Unlike most other cancer-relevant
      signaling pathways, some of the genes in the p53 pathway contain functionally
      significant single nucleotide polymorphisms (SNPs) that alter the amplitude of
      signaling by this protein. These variants, thus, have the potential to impact
      cancer risk, progression, and the efficacy of radiation and chemotherapy. In
      addition, the p53 pathway plays a role in other biological processes, including
      metabolism and reproductive fitness, so these variants have the potential to
      modify other diseases as well. Here we have chosen five polymorphisms in three
      genes in the p53 pathway for review, two in TP53, two in MDM2, and one in MDM4.
      These five variants were selected based on the quality and reproducibility of
      functional data associated with them, as well as the convincingness of
      epidemiological data in support of their association with disease. We also
      highlight two other polymorphisms that may affect p53 signaling, but for which
      functional or association data are still forthcoming (KITLG and ANRIL). Finally,
      we touch on three questions regarding genetic modifiers of the p53 pathway: Why
      did these variants arise? Were they under selection pressure? And, is there
      compelling evidence to support genotyping these variants to better predict
      disease risk and prognosis?

PMID- 27037421
TI  - Erratum: p53 and Medulloblastoma.

PMID- 27037422
TI  - Periprosthetic femoral fractures: a window into some of the challenges we face.

PMID- 27037423
TI  - Decision-making in infected nonunion: is the surgery more important than the
      condition?

PMID- 27037424
TI  - Allergy in total knee arthroplasty: a review of the facts.
AB  - We explored the literature surrounding whether allergy and hypersensitivity has a
      clinical basis for implant selection in total knee arthroplasty (TKA). In error,
      the terms hypersensitivity and allergy are often used synonymously. Although a
      relationship is present, we could not find any evidence of implant failure due to
      allergy. There is however increasing basic science that suggests a link between
      loosening and metal ion production. This is not an allergic response but is a
      potential problem. With a lack of evidence logically there can be no
      justification to use 'hypoallergenic' implants in patients who have pre-existing
      skin sensitivity to the metals used in TKA.

PMID- 27037425
TI  - Assessing the comparability of hip arthroplasty registries in order to improve
      the recording and monitoring of outcome.
AB  - AIMS: We aimed to assess the comparability of data in joint replacement
      registries and identify ways of improving the comparisons between registries and
      the overall monitoring of joint replacement surgery. MATERIALS AND METHODS: We
      conducted a review of registries that are full members of the International
      Society of Arthroplasty Registries with publicly available annual reports in
      English. Of the six registries which were included, we compared the reporting of:
      mean age, definitions for revision and re-operation, reasons for revision, the
      approach to analysing revisions, and patient-reported outcome measures (PROMs)
      for primary and revision total hip arthroplasty (THA) and hip resurfacing
      arthroplasty (HRA). RESULTS: Outcomes were infrequently reported for HRA compared
      with THA and all hip arthroplasties. Revisions were consistently defined, though
      re-operation was defined by one registry. Implant survival was most commonly
      reported as the cumulative incidence of revision using Kaplan-Meier survival
      analysis. Three registries reported patient reported outcome measures.
      CONCLUSION: More consistency in the reporting of outcomes for specific types of
      procedures is needed to improve the interpretation of joint registry data and
      accurately monitor safety trends. As collecting additional details of surgical
      and patient-reported outcomes becomes increasingly important, the experience of
      established registries will be valuable in establishing consistency among
      registries while maintaining the quality of data. TAKE HOME MESSAGE: As the
      volume of joint replacements performed each year continues to increase, greater
      consistency in the reporting of surgical and patient-reported outcomes among
      joint replacement registries would improve the interpretation and comparability
      of these data to monitor outcomes accurately.

PMID- 27037426
TI  - Outcomes of total hip arthroplasty, as a salvage procedure, following failed
      internal fixation of intracapsular fractures of the femoral neck: a systematic
      review and meta-analysis.
AB  - AIMS: The optimal management of intracapsular fractures of the femoral neck in
      independently mobile patients remains open to debate. Successful fixation
      obviates the limitations of arthroplasty for this group of patients. However,
      with fixation failure rates as high as 30%, the outcome of revision surgery to
      salvage total hip arthroplasty (THA) must be considered. We carried out a
      systematic review to compare the outcomes of salvage THA and primary THA for
      intracapsular fractures of the femoral neck. PATIENTS AND METHODS: We performed a
      Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)
      compliant systematic review, using the PubMed, EMBASE and Cochrane libraries
      databases. A meta-analysis was performed where possible, and a narrative
      synthesis when a meta-analysis was not possible. RESULTS: Our analyses revealed a
      significantly increased risk of complications including deep infection, early
      dislocation and peri-prosthetic fracture with salvage THA when compared with
      primary THA for an intracapsular fracture of the femoral neck (overall risk ratio
      of 3.15). Functional outcomes assessment using EuroQoL (EQ)-5D were not
      significantly different (p = 0.3). CONCLUSION: Salvage THA carries a
      significantly higher risk of complications than primary THA for intracapsular
      fractured neck of femur. Current literature is still lacking well designed
      studies to provide a full answer to the question. TAKE HOME MESSAGE: Salvage THA
      is associated with more complications than primary THA for intracapsular neck of
      femur fractures.

PMID- 27037427
TI  - Epidemiology of periprosthetic fracture of the femur in 32 644 primary total hip
      arthroplasties: a 40-year experience.
AB  - AIM AND METHODS: The goals of this study were to define the risk factors, nature,
      chronology, and treatment strategies adopted for periprosthetic femoral fractures
      in 32 644 primary total hip arthroplasties (THAs). RESULTS: There were 564 intra
      operative fractures (1.7%); 529 during uncemented stem placement (3.0%) and 35
      during cemented stem placement (0.23%). Intra-operative fractures were more
      common in females and patients over 65 years (p < 0.001). The majority occurred
      during placement of the femoral component (60%), and involved the calcar (69%).
      There were 557 post-operative fractures (20-year probability: 3.5%; 95%
      confidence interval (CI) 3.2 to 3.9); 335 fractures after placement of an
      uncemented stem (20-year probability: 7.7%; 95% CI 6.2 to 9.1) and 222 after
      placement of a cemented stem (20-year probability: 2.1%; 95% CI 1.8 to 2.5). The
      probability of a post-operative fracture within 30 days after an uncemented stem
      was ten times higher than a cemented stem. The most common post-operative
      fracture type was a Vancouver AG (32%; n = 135), with 67% occurring after a fall.
      In all, 36% (n = 152) were treated with revision arthroplasty. CONCLUSION: In
      summary, intra-operative fractures occur 14 times more often with uncemented
      stems. Female patients over 65 years of age are at highest risk. Post-operative
      fractures are also most common with uncemented stems, but are independent of age
      or gender. Cumulative risk of post-operative periprosthetic femur fracture was
      3.5% at 20 years. TAKE HOME MESSAGE: Intra-operative fractures occur 14 times
      more often with uncemented stems, particularly with female patients over 65 years
      of age, while post-operative fracture risk is independent of age or gender, but
      still increased with uncemented stems.

PMID- 27037428
TI  - Epidemiology of periprosthetic femoral fractures in 5417 revision total hip
      arthroplasties: a 40-year experience.
AB  - AIMS: The goals of this study were to define the risk factors, characteristics,
      and chronology of fractures in 5417 revision total hip arthroplasties (THAs).
      PATIENTS AND METHODS: From our hospital's prospectively collected database we
      identified all patients who had undergone a revision THA between 1969 and 2011
      which involved the femoral stem. The patients' medical records and radiographs
      were examined and the relevant data extracted. Post-operative periprosthetic
      fractures were classified using the Vancouver system. A total of 5417 revision
      THAs were identified. RESULTS: There were 668 intra-operative fractures, giving
      an incidence of 12%. Fractures were three times more common with uncemented stems
      (19%) than with cemented stems (6%) (p < 0.001). The incidence of intra-operative
      femoral fracture varied by uncemented stem type: fully-coated (20%); proximally
      coated (19%); modular fluted tapered (16%) (p < 0.05). Most fractures occurred
      during the insertion of the femoral component (35%). One-third involved the
      diaphysis and 26% were of the calcar: 69% were undisplaced. There were 281 post
      operative fractures of the femur (20-year probability = 11%). There was no
      difference in risk for cemented and uncemented stems. Post-operative fractures
      were more common in men < 70 years (p = 0.02). Periprosthetic fractures occurred
      earlier after uncemented revision of the femoral component, but later after a
      cemented revision. The most common fracture type was a Vancouver B1 (31%). Of all
      post-operative fractures, 24% underwent open reduction and internal fixation and
      15% revision arthroplasty. CONCLUSION: In revision THA, intra-operative fractures
      occurred three times more often with an uncemented stem. Many were undisplaced
      diaphyseal fractures treated with cerclage fixation. While the risk of post
      operative fracture is similar between uncemented and cemented components, they
      occur at notably different times depending on the type of stem fixation. TAKE
      HOME MESSAGE: In revision THA, intra-operative periprosthetic femoral fractures
      occur three times more often with uncemented stems. Many are non-displaced
      diaphyseal fractures treated with cerclage fixation. While postoperative fracture
      risks are equivalent between uncemented and cemented components, they occur at
      notably different time periods based on stem fixation type.

PMID- 27037429
TI  - Enhanced recovery programmes after total hip arthroplasty can result in reduced
      length of hospital stay without compromising functional outcome.
AB  - AIMS: The primary aim of this study was to investigate the effect of an enhanced
      recovery program (ERP) on the short-term functional outcome after total hip
      arthroplasty (THA). Secondary outcomes included its effect on rates of
      dislocation and mortality. PATIENTS AND METHODS: Data were gathered on 1161
      patients undergoing primary THA which included 611 patients treated with
      traditional rehabilitation and 550 treated with an ERP. RESULTS: The ERP was
      shown to be a significant independent factor which shortened length of stay (LOS)
      by a mean of 1.5 days (95% confidence interval (CI) 1.3 to 1.8, p < 0.001) after
      adjusting for confounding variables. The rates of dislocation (traditional 1.03%
      vs ERP 0.91%, p = 0.84) and mortality (1.5% vs 0.6%, p = 0.14) one year post
      operatively were not significantly different. Both groups showed significant
      improvement in Harris Hip Score (42.8 vs 41.5) at 12 to 18 months post
      operatively and there was no significant difference in the magnitude of
      improvement on univariate (p = 0.09) and multivariate analysis (p = 0.35). There
      was no significant difference in any of the eight domain scores of the Short-Form
      - 36 general health surveys post-operatively (p > 0.38). CONCLUSION: We conclude
      that an ERP after THA shortens LOS by a mean of 1.5 days and does not increase
      the rate of complications post-operatively. It gives equivalent functional
      outcomes to a traditional rehabilitation pathway. TAKE HOME MESSAGE: ERP reduces
      LOS after THA in comparison to traditional rehabilitation, without adversely
      affecting functional outcomes, dislocation rates or mortality.

PMID- 27037430
TI  - Radiological characteristics of the knee joint in nail patella syndrome.
AB  - AIM: Nail patella syndrome (NPS) is a skeletal dysplasia with patellofemoral
      dysfunction as a key symptom. We present the first in-depth radiological
      evaluation of the knee in a large series of NPS patients and describe the typical
      malformations. PATIENTS AND METHODS: Conventional radiological examination of 95
      skeletally mature patients with NPS was performed. Patellar morphology was
      classified according to the Wiberg classification as modified by Baumgartl and
      Ficat criteria, and trochlear shape was classified according to the Dejour
      classification. RESULTS: Patellar aplasia was present in 4/90 (4%), and patellar
      hypoplasia in 77/90 (86%) of patients. The prevailing patellar shapes were type
      III, type IV and Hunter's cap. No patellar shape genotype-phenotype association
      could be found. The malformations of the distal femur comprised shortening of the
      lateral femoral condyle in 46 out of 84 patients (55%), with a prominent anterior
      surface of the lateral femoral condyle in 47 out of 84 patients (56%) and a flat
      anterior surface of the medial femoral condyle in 78 out of 85 patients (92%).
      The trochlea was type A1 according to the Dejour classification in 79 out of 85
      patients (93%). CONCLUSION: An easily recognisable characteristic quartet of
      malformations consisting of patellar aplasiaor hypoplasia and the malformations
      of the distal femur was found in 22 out of 81 patients (27%), with the majority
      displaying at least three malformations. TAKE HOME MESSAGE: The distinct
      malformations of the knee in nail patella syndrome are easily recognisable on
      conventional radiographs and lead to the correct interpretation of the aberrant
      morphology which is essential in the treatment of these patellofemoral disorders.

PMID- 27037431
TI  - The pre-operative levels of haemoglobin in the blood can be used to predict the
      risk of allogenic blood transfusion after total knee arthroplasty.
AB  - AIMS: The pre-operative level of haemoglobin is the strongest predictor of the
      peri-operative requirement for blood transfusion after total knee arthroplasty
      (TKA). There are, however, no studies reporting a value that could be considered
      to be appropriate pre-operatively. This study aimed to identify threshold pre
      operative levels of haemoglobin that would predict the requirement for blood
      transfusion in patients who undergo TKA. PATIENTS AND METHODS: Analysis of
      receiver operator characteristic (ROC) curves of 2284 consecutive patients
      undergoing unilateral TKA was used to determine gender specific thresholds
      predicting peri-operative transfusion with the highest combined sensitivity and
      specificity (area under ROC curve 0.79 for males; 0.78 for females). RESULTS:
      Threshold levels of 13.75 g/dl for males and 12.75 g/dl for females were
      identified. The rates of transfusion in males and females, respectively above
      these levels were 3.37% and 7.11%, while below these levels, they were 16.13% and
      28.17%. Pre-operative anaemia increased the rate of transfusion by 6.38 times in
      males and 6.27 times in females. Blood transfusion was associated with an
      increased incidence of early post-operative confusion (odds ratio (OR) = 3.44),
      cardiac arrhythmia (OR = 5.90), urinary catheterisation (OR = 1.60), the
      incidence of deep infection (OR = 4.03) and mortality (OR = 2.35) one year post
      operatively, and increased length of stay (eight days vs six days, p < 0.001).
      CONCLUSION: Uncorrected low pre-operative levels of haemoglobin put patients at
      potentially modifiable risk and attempts should be made to correct this before
      TKA. Target thresholds for the levels of haemoglobin pre-operatively in males and
      females are proposed. TAKE HOME MESSAGE: Low pre-operative haemoglobin levels put
      patients at unnecessary risk and should be corrected prior to surgery.

PMID- 27037432
TI  - Corticosteroid injection for Morton's neuroma with or without ultrasound
      guidance: a randomised controlled trial.
AB  - AIMS: The objective of this double-blind randomised controlled trial was to
      assess whether ultrasound guidance improved the efficacy of corticosteroid
      injections for Morton's neuroma (MN). PATIENTS AND METHODS: In all, 50 feet (40
      patients) were recruited for this study but five feet were excluded due to the
      patients declining further participation. The mean age of the remaining 36
      patients (45 feet) was 57.8 years (standard deviation (sd) 12.9) with a female
      preponderance (33F:12M). All patients were followed-up for 12 months. Treatment
      was randomised to an ultrasound guided (Group A) or non-ultrasound guided (Group
      B) injection of 40 mg triamcinolone acetonide and 2 ml 1% lignocaine, following
      ultrasound confirmation of the diagnosis. RESULTS: The mean visual analogue score
      for pain improved significantly in both groups (Group A - from 64 mm, sd 25 mm to
      29 mm, sd 27; Group B - from 69 mm, sd 23 mm to 37 mm, sd 25) with no statistical
      difference between them at all time-points. The failure rate within 12 months of
      treatment was 11/23 (48%) and 12/22 (55%) in Groups A and B, respectively (p =
      0.458). The improvement in Manchester Oxford Foot Questionnaire Index and patient
      satisfaction favoured Group A in the short-term (three months) that almost
      reached statistical significance (p = 0.059 and 0.066 respectively). However,
      this difference was not observed beyond three months. CONCLUSION: This study has
      shown that ultrasound guidance did not demonstrably improve the efficacy of
      corticosteroid injections in patients with MN. TAKE HOME MESSAGE: In the presence
      of a clear diagnosis of MN, a trained clinician who understands the forefoot
      anatomy may perform an injection without ultrasound guidance with good and safe
      results.

PMID- 27037433
TI  - Histological evaluation of two designs of shoulder surface replacement implants.
AB  - AIMS: To assess the extent of osteointegration in two designs of shoulder
      resurfacing implants. Bony integration to the Copeland cylindrical central stem
      design and the Epoca RH conical-crown design were compared. PATIENTS AND METHODS:
      Implants retrieved from six patients in each group were pair-matched. Mean time
      to revision surgery of Copeland implants was 37 months (standard deviation (sd)
      23; 14 to 72) and Epoca RH 38 months (sd 28; 12 to 84). The mean age of patients
      investigated was 66 years (sd 4; 59 to 71) and 58 years (sd 17; 31 to 73) in the
      Copeland and Epoca RH groups respectively. None of these implants were revised
      for loosening. RESULTS: Increased osteointegration was measured under the cup in
      the Copeland implant group with limited bone seen in direct contact with the
      central stem. Bone adjacent to the Epoca RH implants was more uniform.
      CONCLUSION: This difference in the distribution of bone-implant contact and bone
      formation was attributed to the Epoca implant's conical crown, which is
      positioned in more dense peripheral bone. The use of a central stem may not be
      necessary provided there is adequate peripheral fixation within good quality
      humeral bone. TAKE HOME MESSAGE: Poor osteointegration of cementless surface
      replacement shoulder prosthesis may be improved by implant design.

PMID- 27037434
TI  - Radiographic failure and rates of re-operation after acromioclavicular joint
      reconstruction: a comparison of surgical techniques.
AB  - AIMS: To compare radiographic failure and re-operation rates of anatomical
      coracoclavicular (CC) ligament reconstructional techniques with non-anatomical
      techniques after chronic high grade acromioclavicular (AC) joint injuries.
      PATIENTS AND METHODS: We reviewed chronic AC joint reconstructions within a
      region-wide healthcare system to identify surgical technique, complications,
      radiographic failure and re-operations. Procedures fell into four categories: (1)
      modified Weaver-Dunn, (2) allograft fixed through coracoid and clavicular
      tunnels, (3) allograft loop coracoclavicular fixation, and (4) combined allograft
      loop and synthetic cortical button fixation. Among 167 patients (mean age 38.1
      years, (standard deviation (sd) 14.7) treated at least a four week interval after
      injury, 154 had post-operative radiographs available for analysis. RESULTS:
      Radiographic failure occurred in 33/154 cases (21.4%), with the lowest rate in
      Technique 4 (2/42 4.8%, p = 0.001). Half the failures occurred by six weeks, and
      the Kaplan-Meier survivorship at 24 months was 94.4% (95% confidence interval
      (CI) 79.6 to 98.6) for Technique 4 and 69.9% (95% CI 59.4 to 78.3) for the other
      techniques when combined. In multivariable survival analysis, Technique 4 had
      better survival than other techniques (Hazard Ratio 0.162, 95% CI 0.039 to 0.068,
      p = 0.013). Among 155 patients with a minimum of six months post-operative
      insurance coverage, re-operation occurred in 9.7% (15 patients). However, in
      multivariable logistic regression, Technique 4 did not reach a statistically
      significant lower risk for re-operation (odds ratio 0.254, 95% CI 0.05 to 1.3, p
      = 0.11). CONCLUSION: In this retrospective series, anatomical CC ligament
      reconstruction using combined synthetic cortical button and allograft loop
      fixation had the lowest rate of radiographic failure. TAKE HOME MESSAGE:
      Anatomical coracoclavicular ligament reconstruction using combined synthetic
      cortical button and allograft loop fixation had the lowest rate of radiographic
      failure.

PMID- 27037435
TI  - A single blind randomised controlled trial of the impact on patient-reported pain
      of arm elevation versus exsanguination prior to tourniquet inflation.
AB  - AIMS: The aim of this study was to compare the pain caused by the application of
      a tourniquet after exsanguination of the upper limb with that occurring after
      simple elevation. PATIENTS AND METHODS: We used 26 healthy volunteers (52 arms),
      each of whom acted as their own matched control. The primary outcome measure was
      the total pain experienced by each volunteer while the tourniquet was inflated
      for 20 minutes. This was calculated as the area under the pain curve for each
      individual subject. Secondary outcomes were pain at each time point; the total
      pain experienced during the recovery phase; the ability to tolerate the
      tourniquet and the time for full recovery after deflation of the tourniquet.
      RESULTS: There was a significant difference in the area under the pain curves in
      favour of exsanguination (mean difference 8.4; 95% confidence interval (CI) 3.0
      to 13.7, p = 0.004). There was no difference between the dominant and non
      dominant arms (mean difference -0.2; 95% CI -23.2 to 22.8, p = 0.99). The area
      under both recovery curves were similar (mean difference 0.7; 95% CI -6.0 to 4.6,
      p = 0.78). There was no statistical difference in recovery time, the actual mean
      difference being 30 seconds longer in the elevation group (p = 0.06). CONCLUSION:
      Many orthopaedic and plastic surgery procedures are done under local anaesthetic
      or regional block where a bloodless field and a motionless patient are essential.
      Optimising patient comfort during surgery with the tourniquet inflated is thus a
      priority. This study is useful in that it compares two common methods of
      preparation of the upper limb prior to tourniquet inflation and which have not
      previously been compared in this context. Following on the results of this study,
      we can confidently conclude that exsanguinating the upper limb before inflating a
      tourniquet is more comfortable than simply elevating the arm for patients
      undergoing a procedure under local or regional block, both during the procedure
      and in the recovery phase. TAKE HOME MESSAGE: Exsanguination rather than
      elevation is recommended in order to minimise patient discomfort and optimise the
      surgical field.

PMID- 27037436
TI  - Coccygectomy for patients with chronic coccydynia: a prospective, observational
      study of 98 patients.
AB  - AIMS: The purpose of this prospective study was to evaluate the outcomes of
      coccygectomy for patients with chronic coccydynia. PATIENTS AND METHODS: Between
      2007 and 2011, 98 patients underwent coccygectomy for chronic coccydynia. The
      patients were aged > 18 years, had coccygeal pain, local tenderness and a
      radiological abnormality, and had failed conservative management. Outcome
      measures were the Short Form 36 (SF-36), the Oswestry Disability Index (ODI) and
      a visual analogue scale (VAS) for pain. Secondary analysis compared the pre
      operative features and the outcomes of patients with successful and failed
      treatment, two years post-operatively. The threshold for success was based on a
      minimum clinically important difference (MCID) on the ODI of 20 points. All other
      patients, including those lost to follow-up, were classified as failures.
      RESULTS: There was significant improvement in all ten components of the SF-36 (p
      < 0.05), the ODI (23 points) and VAS (39 points) (p < 0.0001). A total of 69
      patients (70.4%) met the designated MCID threshold for a successful outcome. The
      failure group consisted of 25 patients (25.5%) who did not reach the MCID and
      four (4.1%) who were lost to follow-up. Six patients (6.1%) in the failure group
      had ODI scores that were no better or worse than that pre-operatively. The
      patients in whom treatment failed had significantly worse pre-operative scores
      for the ODI (p = 0.04), VAS (p = 0.02) and on five of ten SF-36 components (p <
      0.04). They also had a higher incidence of psychiatric disorders, pre-operative
      opiate use and more than three comorbidities. TAKE HOME MESSAGE: Coccygectomy for
      chronic coccydynia results in significant improvement in patient-reported
      outcomes at two years. Failure is associated with certain pre-operative
      characteristics such as psychiatric illness, poor quality of life features,
      higher levels of pain, and use of opiates.

PMID- 27037437
TI  - Exchange nailing for nonunion of diaphyseal fractures of the tibia: our results
      and an analysis of the risk factors for failure.
AB  - AIMS: The aim of this study was to identify risk factors for the failure of
      exchange nailing in nonunion of tibial diaphyseal fractures. PATIENTS AND
      METHODS: A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean
      age of 36.9 years (15 to 74) were treated between January 1992 and December 2012
      by exchange nailing. Of which 33 (32%) were initially open injuries. The median
      time from primary fixation to exchange nailing was 6.5 months (interquartile
      range (IQR) 4.3 to 9.8 months). The main outcome measures were union, number of
      secondary fixation procedures required to achieve union and time to union.
      Univariate analysis and multiple regression were used to identify risk factors
      for failure to achieve union. RESULTS: Multiple causes for the primary nonunion
      were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients
      were lost to follow-up. Further surgical procedures were required in 35 (36%)
      nonunions. Other fixation modalities were required in five fractures. A single
      nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11
      out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up
      to five repeated exchange nailings, with or without bone grafting, ultimately
      achieved union in 89 (93%) fractures. The median time to union after exchange
      nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed
      that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm
      or more (p = 0.04) and infection (p < 0.001), were predictive for failure of
      exchange nailing Multiple regression analysis found that infection was the
      strongest predictor of failure (p < 0.001). CONCLUSION: Exchange nailing is an
      effective treatment for aseptic tibial diaphyseal nonunion. However, in the
      presence of severe infection with a highly resistant organism, or extensive
      sclerosis of the bone, other fixation modalities, such as Ilizarov treatment,
      should be considered. TAKE HOME MESSAGE: Exchange nailing is an effective
      treatment for aseptic tibial diaphyseal nonunion.

PMID- 27037438
TI  - The surgical approach for hemiarthroplasty does not influence patient-reported
      outcome : a national survey of 2118 patients with one-year follow-up.
AB  - AIMS: Hemiarthroplasty of the hip is usually carried out through either a direct
      lateral or posterior approach. The aim of this prospective observational study
      was to determine any differences in patient-reported outcomes between the two
      surgical approaches. PATIENTS AND METHODS: From the Swedish Hip Arthroplasty
      Register we identified patients of 70 years and above who were recorded as having
      had a hemiarthroplasty during 2009. Only patients who had been treated with
      modern prostheses were included. A questionnaire was posted to those who remained
      alive one year after surgery. A total of 2118 patients (78% of those available)
      with a mean age of 85 years (70 to 102) returned the questionnaire. RESULTS:
      Patients who had undergone surgery through a posterior approach reported a higher
      health-related quality of life (HRQoL, EQ-5D mean 0.52 versus 0.47, p = 0.009),
      less pain (visual analogue scale mean 17 versus 19, p = 0.02) and greater
      satisfaction with the result of surgery (visual analogue scale mean 22 versus 24,
      p = 0.02) than those who had a direct lateral approach. However, after adjusting
      for age, gender, cognitive impairment and American Society of Anesthesiologists
      grade, no association was found between surgical approach and HRQoL, residual
      pain or patient satisfaction. TAKE HOME MESSAGE: The surgical approach for
      hemiarthroplasty does not seem to affect the patient-perceived HRQoL, residual
      pain or patient satisfaction one year after surgery on elderly patients. The
      choice of approach should be based on other factors, such as the risk of
      dislocation.

PMID- 27037439
TI  - Amputation in patients with complex regional pain syndrome: a comparative study
      between amputees and non-amputees with intractable disease.
AB  - AIMS: Amputation in intractable cases of complex regional pain syndrome (CRPS)
      remains controversial. The likelihood of recurrent Complex Regional Pain Syndrome
      (CRPS), residual and phantom limb pain and persistent disability after amputation
      is poorly described in the literature. The aims of this study were to compare
      pain, function, depression and quality of life between patients with intractable
      CRPS who underwent amputation and those in whom amputation was considered but not
      performed. PATIENTS AND METHODS: There were 19 patients in each group, with
      comparable demographic details. The amputated group included 14 men and five
      women with a mean age of 31 years (sd 12) at the time of CRPS diagnosis. The non
      amputated group consisted of 12 men and seven women and their mean age of 36.8
      years (sd 8) at CRPS diagnosis. The mean time from CRPS diagnosis to (first)
      amputation was 5.2 years (sd 4.3) and the mean time from amputation to data
      collection was 6.6 years (sd 5.8). All participants completed the following
      questionnaires: Short-Form (SF) 36, Short Form McGill Pain questionnaire (SF
      MPQ), Pain Disability Index (PDI), the Beck Depression Inventory (BDI) and a
      clinical demographic questionnaire. RESULTS: The amputation group showed
      consistently better results compared to the non-amputation group in the following
      parameters: median pain intensity (VAS): 80 (inter-quartile range (IQR) 13 to 92)
      vs 91 (IQR 85 to 100); p = 0.007; median SF-MPQ score 28 (IQR 9 to 35) vs 35 (IQR
      31 to 38), p = 0.025; median PDI: 42 (IQR 11 to 64) vs 58 (IQR 50 to 62), p =
      0.031; median BDI: 19 (IQR 5 to 28) vs 27 (IQR 21 to 32), p = 0.061 (borderline
      significant) and in six of the eight SF-36 domains. TAKE HOME MESSAGE: Amputation
      should be considered as a form of treatment for patients with intractable CRPS.

PMID- 27037440
TI  - Osteosarcoma of the pelvis.
AB  - AIMS: Osteosarcoma of the pelvis is a particularly difficult tumour to treat as
      it often presents late, may be of considerable size and/or associated with
      metastases when it presents, and is frequently chondroid in origin and resistant
      to chemotherapy. The aim of this study was to review our experience of managing
      this group of patients and to identify features predictive of a poor outcome.
      PATIENTS AND METHODS: Between 1983 and 2014, 121 patients, (74 females and 47
      males) were treated at a single hospital: 74 (61.2%) patients had a primary
      osteosarcoma and 47 (38.8%) had an osteosarcoma which was secondary either to
      Paget's disease (22; 18.2%) or to previous pelvic irradiation (25; 20.7%). The
      mean age of those with a primary osteosarcoma was 29.3 years (nine to 76) and
      their mean follow-up 2.9 years (0 to 29). The mean age of those with a secondary
      sarcoma was 61.9 years (15 to 85) and their mean follow-up was one year (0 to
      14). A total of 22 patients with a primary sarcoma (52.4%) and 20 of those with a
      secondary sarcoma (47.6%) had metastases at the time of presentation. RESULTS:
      The disease-specific survival at five years for all patients was 27.2%. For those
      without metastases at the time of diagnosis, the five-year survival was 32.7%.
      Factors associated with a poor outcome were metastases at diagnosis and secondary
      tumours. In primary osteosarcoma, sacral location, surgical margin and a diameter
      > 10 cm were associated with a poor outcome. CONCLUSION: In this, the largest
      single series of patients with an osteosarcoma of the pelvis treated in a single
      hospital, those with secondary tumours and those with metastases at presentation
      had a particularly poor outcome. For those with a primary sarcoma, sacral
      location, an intralesional margin and a diameter of > 10 cm were poor prognostic
      indicators.

PMID- 27037441
TI  - An investigation into the aetiology of flexible flat feet: the role of subtalar
      joint morphology.
AB  - AIMS: There is increasing evidence that flexible flatfoot (FF) can lead to
      symptoms and impairment in health-related quality of life. As such we undertook
      an observational study investigating the aetiology of this condition, to help
      inform management. The hypothesis was that as well as increased body mass index
      (BMI) and increased flexibility of the lower limb, an absent anterior subtalar
      articulation would be associated with a flatter foot posture. PATIENTS AND
      METHODS: A total of 84 children aged between eight and 15 years old were
      prospectively recruited. The BMI for each child was calculated, flexibility was
      assessed using the lower limb assessment scale (LLAS) and foot posture was
      quantified using the arch height index (AHI). Each child underwent a sagittal T1
      weighted MRI scan of at least one foot. RESULTS: An absent anterior subtalar
      articulation (p < 0.001) and increased LLAS (p = 0.001) predicted a low AHI. BMI
      was not a significant predictive factor (p = 0.566). CONCLUSION: This is the
      first study to demonstrate the importance of the morphology of the subtalar joint
      on the underlying foot posture in vivo. TAKE HOME MESSAGE: Flexibility of the
      lower limb and absence of the anterior facet of the subtalar joint are associated
      with flexible FF and may influence management of this common condition.

PMID- 27037442
TI  - The outcome and prognostic factors in children with bilateral Perthes' disease: a
      prospective study of 40 children with follow-up over five years.
AB  - AIMS: The aims of this study were to describe the course of non-operatively
      managed, bilateral Perthes' disease, and to determine specific prognostic factors
      for the radiographic and clinical outcome. PATIENTS AND METHODS: We identified 40
      children with a mean age of 5.9 years (1.8 to 13.5), who were managed non
      operatively for bilateral Perthes' disease from our prospective, multicentre
      study of this condition, which included all children in Norway who were diagnosed
      with Perthes' disease in the five-year period between 1996 and 2000. All children
      were followed up for five years. The hips were classified according to the
      Catterall classification. A modified three-group Stulberg classification was used
      as an outcome measure, with a spherical femoral head being defined as a good
      outcome, an oval head as fair, and a flat femoral head as a poor outcome.
      RESULTS: Concurrent, simultaneous bilateral Perthes' disease was seen in 23
      children and 17 had the sequential onset of bilateral disease. The mean delay in
      onset for the second hip in the latter group was 1.9 years (0.3 to 5.5). The five
      year radiographic outcome was good in 30 (39%), fair in 25 (33%) and poor in 21
      (28%) of the hips. The strongest predictors of poor outcome were > 50% necrosis
      of the femoral head, with odds ratio (OR) 19.6, and age at diagnosis > 6 years
      (OR 3.3). Other risk factors for poor outcome were the timing of the onset of
      disease, where children with the sequential onset of bilateral disease had a
      higher risk than those with the concurrent onset of bilateral disease (p = 0.021,
      chi-squared test). Following a diagnosis of Perthes' disease in one hip, there
      was a 5% chance of developing it in the contralateral hip. CONCLUSION: These
      results imply that we need to distinguish between children with concurrent onset
      and those with sequential onset of bilateral Perthes' disease, as the outcomes
      may be different. This has not been previously described. Children with
      concurrent onset of bilateral disease had a similar outcome to our previous
      series of those with unilateral disease, whereas children with sequential onset
      of bilateral disease had a worse prognosis. The increased risk of developing
      Perthes' disease in the contralateral hip in those with unilateral disease is
      important information for the child and parents.

PMID- 27037443
TI  - Errata/Corrigenda.

PMID- 27037444
TI  - I Spent How Many Hours in a Classroom?!

PMID- 27037445
TI  - Feasibility Study for a Satellite Program of an Established School of Dentistry.
AB  - Creative thinking is required to solve the many challenges the oral health care
      delivery system faces in meeting the needs of the U.S. POPULATION: Access to oral
      health care services varies widely across the country based on a host of factors
      including individual patient characteristics, demographic variables, and
      distribution of professionals by locale. There is also significant variability of
      need, so that many new solutions have been proposed to meet the needs of specific
      areas. In late 2012, the University of Missouri-Kansas City School of Dentistry
      embarked on a feasibility study to determine whether its existing DDS program
      could be extended closer to underserved areas of Missouri and surrounding regions
      by utilizing distance education and a clinical training facility in conjunction
      with another public university. This article describes the study and its
      outcomes. Other institutions may find this process useful as they assess factors
      that could impact the success of future programming and seek new solutions to
      long-standing problems.

PMID- 27037446
TI  - Modern Management Principles Come to the Dental School.
AB  - The University of Washington School of Dentistry may be the first dental school
      in the nation to apply lean process management principles as a primary tool to re
      engineer its operations and curriculum to produce the dentist of the future. The
      efficiencies realized through re-engineering will better enable the school to
      remain competitive and viable as a national leader of dental education. Several
      task forces conducted rigorous value stream analyses in a highly collaborative
      environment led by the dean of the school. The four areas undergoing evaluation
      and re-engineering were organizational infrastructure, organizational processes,
      curriculum, and clinic operations. The new educational model was derived by
      thoroughly analyzing the current state of dental education in order to design and
      achieve the closest possible ideal state. As well, the school's goal was to
      create a lean, sustainable operational model. This model aims to ensure continued
      excellence in restorative dental instruction and to serve as a blueprint for
      other public dental schools seeking financial stability in this era of shrinking
      state support and rising costs. 

PMID- 27037447
TI  - Practice Location Characteristics of Non-Traditional Dental Practices.
AB  - Current and future dental school graduates are increasingly likely to choose a
      non-traditional dental practice-a group practice managed by a dental service
      organization or a corporate practice with employed dentists-for their initial
      practice experience. In addition, the growth of non-traditional practices, which
      are located primarily in major urban areas, could accelerate the movement of
      dentists to those areas and contribute to geographic disparities in the
      distribution of dental services. To help the profession understand the
      implications of these developments, the aim of this study was to compare the
      location characteristics of non-traditional practices and traditional dental
      practices. After identifying non-traditional practices across the United States,
      the authors located those practices and traditional dental practices
      geographically by zip code. Non-traditional dental practices were found to
      represent about 3.1% of all dental practices, but they had a greater impact on
      the marketplace with almost twice the average number of staff and annual revenue.
      Virtually all non-traditional dental practices were located in zip codes that
      also had a traditional dental practice. Zip codes with non-traditional practices
      had significant differences from zip codes with only a traditional dental
      practice: the populations in areas with non-traditional practices had higher
      income levels and higher education and were slightly younger and proportionally
      more Hispanic; those practices also had a much higher likelihood of being located
      in a major metropolitan area. Dental educators and leaders need to understand the
      impact of these trends in the practice environment in order to both prepare
      graduates for practice and make decisions about planning for the workforce of the
      future. 

PMID- 27037448
TI  - Identifying Multilevel Barriers to Tobacco Intervention in Postdoctoral Dental
      Education.
AB  - The aims of this mixed-methods study were to assess tobacco treatment behaviors
      among residents and faculty in dental specialty postdoctoral programs and to
      explore factors in training and practice related to tobacco treatment education.
      Surveys and focus groups were conducted with a convenience sample of participants
      at three postdoctoral residency programs in New York City. Surveys assessed
      tobacco cessation training and behaviors. Focus groups explored barriers to
      implementing tobacco cessation treatment in educational settings. Data were
      collected between May and December 2013. Among the 160 faculty and residents
      identified as potentially eligible for the study, 60 were invited by program
      directors to participate, and 50 subsequently completed the survey and
      participated in a focus group (response rate of 31.3%). Survey results indicated
      high levels of asking patients about tobacco use and advising patients to quit.
      In contrast, specific tobacco cessation assistance and follow-up care occurred
      less frequently. There were statistically significant differences in tobacco
      cessation intervention across the specialties surveyed, but not between residents
      and faculty. Focus group comments were grouped into three broad areas: clinician
      factors, organizational support, and structural and contextual factors. Focus
      group results indicated that participants experienced significant organizational
      and structural barriers to learning about and providing tobacco treatment.
      Participants from each specialty indicated that multi-level barriers impeded
      their provision of evidence-based tobacco cessation interventions in postdoctoral
      educational settings. They suggested that didactic education should be reinforced
      by organizational- and systems-level changes to facilitate comprehensive tobacco
      education and effective cessation treatment in future dental practice. 

PMID- 27037449
TI  - Impact on Junior Faculty of Teaching Opportunities During Predoctoral Education:
      A Survey-Based Study.
AB  - Dental schools have addressed full-time faculty shortages by utilizing part-time
      faculty and postdoctoral students as teachers. Studies have also shown that peer
      tutors in dental schools can be used effectively in addition to or in place of
      faculty, but there has been little research on whether the peer tutoring
      experience influences tutors to pursue academic careers. This study surveyed
      junior faculty at 60 U.S. dental schools about their predoctoral tutoring and
      teaching experiences. Data from 122 respondents were analyzed. The results
      indicated that more recent graduates had more peer tutoring opportunities
      available than those who graduated prior to the 1980s and that the teaching
      experiences influenced the respondents' decisions to pursue academic careers.
      Additionally, those peer tutoring programs that placed more responsibility on the
      peer tutors, signifying trust from the institution, were the most successful in
      influencing respondents' decisions to pursue academia. Finally, when comparing
      their predoctoral teaching experiences to faculty development of teaching skills
      at their current institutions, the majority of the respondents reported that the
      faculty development was better. However, the peer tutoring programs considered
      equal to or better than faculty development were more influential in stimulating
      participants' academic career interest. These results suggest that dental schools
      can look to peer tutoring and teaching programs to stimulate students' interest
      in academia that can help reduce faculty shortages in the long term, but only if
      programs are developed that place greater responsibility and trust in students
      and that equal the quality of faculty development programs. 

PMID- 27037450
TI  - Reaching Consensus on Essential Biomedical Science Learning Objectives in a
      Dental Curriculum.
AB  - This article describes how the University of British Columbia Faculty of
      Dentistry reached consensus on essential basic biomedical science objectives for
      DMD students and applied the information to the renewal of its DMD curriculum.
      The Delphi Method was used to build consensus among dental faculty members and
      students regarding the relevance of over 1,500 existing biomedical science
      objectives. Volunteer panels of at least three faculty members (a basic
      scientist, a general dentist, and a dental specialist) and a fourth-year dental
      student were formed for each of 13 biomedical courses in the first two years of
      the program. Panel members worked independently and anonymously, rating each
      course objective as "need to know," "nice to know," "irrelevant," or "don't
      know." Panel members were advised after each round which objectives had not yet
      achieved a 75% consensus and were asked to reconsider their ratings. After a
      maximum of three rounds to reach consensus, a second group of faculty experts
      reviewed and refined the results to establish the biomedical science objectives
      for the renewed curriculum. There was consensus on 46% of the learning objectives
      after round one, 80% after round two, and 95% after round three. The second
      expert group addressed any remaining objectives as part of its review process.
      Only 47% of previous biomedical science course objectives were judged to be
      essential or "need to know" for the general dentist. The consensus reached by
      participants in the Delphi Method panels and a second group of faculty experts
      led to a streamlined, better integrated DMD curriculum to prepare graduates for
      future practice. 

PMID- 27037451
TI  - Evidence-Based Practice Knowledge, Perceptions, and Behavior: A Multi
      Institutional, Cross-Sectional Study of a Population of U.S. Dental Students.
AB  - The aim of this study was to help inform faculty and curriculum leaders in
      academic dental institutions about the knowledge, skills, perceptions, and
      behavior of an institutionally diverse population of dental students with respect
      to evidence-based practice (EBP). A survey utilizing the validated Knowledge,
      Attitudes, Access, and Confidence Evaluation instrument developed by Hendricson
      et al. was conducted in 2012 with fourth-year dental students at seven
      geographically dispersed U.S. dental schools. The survey addressed elements of
      EBP knowledge, attitudes toward EBP, behavior in accessing evidence, and
      perceptions of competence in statistical analysis. A total of 138 students from
      the seven schools participated. A slight majority of these students correctly
      responded to the knowledge of critical appraisal questions. While the students
      demonstrated positive attitudes about EBP, they did not report high levels of
      confidence in their critical appraisal skills. The findings also showed that the
      students accessed various sources of evidence with differing frequencies. The
      most frequently accessed resources were colleagues, the Internet (excluding
      Cochrane Database of Systematic Reviews), and textbooks. The results of this
      study help to identify areas for improvement in EBP education in order to advance
      dental students' preparation to become evidence-based practitioners. 

PMID- 27037452
TI  - Student Evaluations of Teaching: Dental and Dental Hygiene Students' and Faculty
      Members' Perspectives.
AB  - The aim of this study was to explore dental and dental hygiene students' and
      faculty members' perceptions of student evaluations of teaching (SET) and
      determine whether dental vs. dental hygiene student, beginning vs. advanced
      student, and faculty vs. student responses differed. Perceived benefits,
      challenges, and suggestions for conducting SETs optimally were also assessed.
      Survey data were collected from 329 dental students (D1: 108; D2: 91; D3&4: 130)
      and 68 dental hygiene students (DH2: 26; DH3: 19; DH4: 23) (overall response
      rates 76%/92%) and 56 dental and eight dental hygiene faculty members (response
      rates 41%/100%). Faculty respondents were more positive about SETs than students
      (five-point scale with 1=disagree: 3.85 vs. 3.39; p<0.001), with seniors being
      the least positive (mean 2.42). Respondents agreed that all students should
      complete SETs (3.87 vs. 3.61; p=0.068), with faculty agreeing more strongly than
      students that all courses should be evaluated (4.32/4.04; p=0.046). Students
      agreed more strongly than faculty that SETs should occur during regular class
      time (3.97/3.44; p<0.001) and are too long (3.47/3.09; p=0.010) and that results
      should be shared with students (4.03/3.57; p=0.002). Open-ended responses showed
      that students perceived more benefits of SETs for faculty members than for
      students and that the most frequently mentioned problem was that SETs do not
      result in changes. Faculty members were generally more positive than students
      (especially seniors) about SETs. These findings suggest that, according to these
      respondents, SETs should be completed by all students for all courses, be short,
      provide opportunities for open-ended comments, and be administered in class to
      improve response rate. In addition, SET results and how SETs are used to improve
      courses should be shared with students. 

PMID- 27037453
TI  - Relationship Among Dental Students' Class Lecture Attendance, Use of Online
      Resources, and Performance.
AB  - This study aimed to evaluate the relationship among dental students' attendance
      at class lectures, use of online lecture materials, and performance in didactic
      courses. The study was conducted with second-year predoctoral students at Tufts
      University School of Dental Medicine during the fall semester of 2014. Three
      basic science and three preclinical dental courses were selected for evaluation.
      Online usage for each participant was collected, and a survey with questions
      about attendance and online behavior was conducted. The final grade for each
      participant in each selected course was obtained and matched with his or her
      online usage and attendance. Out of a total 190 students, 146 (77%) participated.
      The results showed no significant relationship between students' grades and their
      class attendance or online usage except for a weak negative relationship between
      class attendance and online usage for the Epidemiology course (p<0.001) and the
      overall preclinical dental courses (p=0.03). Although the results did not show
      strong relationships among class attendance, online usage, and course grades,
      most of the students reported that having the online resources in addition to the
      lectures was helpful. 

PMID- 27037454
TI  - Educational Outcomes of Small-Group Discussion Versus Traditional Lecture Format
      in Dental Students' Learning and Skills Acquisition.
AB  - The aim of this prospective quantitative study was to compare the effect of
      different instructional formats on dental students' skills and knowledge
      acquisition for access cavity preparation. All first-year dental students were
      invited to participate in this study conducted during the four consecutive two
      week endodontic rotation courses at the University of the Pacific Arthur A.
      Dugoni School of Dentistry in spring semester 2015. Four alphabetically
      distributed intact groups of students were randomly allocated to two groups (n=70
      each) that participated in either small-group discussion or a traditional lecture
      on access preparation. The first outcome measure was skill acquisition, measured
      by the quality of access cavities prepared in extracted teeth at the conclusion
      of the session. Two blinded raters scored direct observations on a continuous
      scale. Knowledge, the second outcome measure, was scored with a multiple-choice
      and open-ended question test at the end of each two-week session. Data were
      obtained for 134 of the 140 students, for a 96% response rate. The results showed
      that students in the small-group discussion groups scored significantly higher
      than those in the lecture groups when skill performance was tested (p=8.9 * 10(
      7)). However, no significant differences were found in the acquisition of
      knowledge between the two groups on the written test. Active student
      participation was significantly related to improved manual skill acquisition, but
      the format of the session does not seem to have had a direct influence on
      acquired knowledge. 

PMID- 27037455
TI  - Conversation Salons: A Flexible Format for Open Discourse in Dental Education.
AB  - A series of conversation salons was created at the University of Minnesota School
      of Dentistry as an innovative format with the objective of engaging students,
      faculty, staff, and practitioners in discussion to promote reflection. The aim of
      this study was to explore the nature of students' abilities in the salons to
      connect experiences through reflection and apply what they learned to practice.
      Reflective essays (written during the summer and fall semesters of 2014) from 108
      fourth-year dental students (all members of the Class of 2015) were read and
      assessed for the nature of reflection, number of connections, references to the
      past, applications to the future, and use of examples. For analysis, the
      theoretical works of Schon and Mezirow provided a useful framework. Overall, the
      results showed that the participants found the salon experience to be positive,
      and student participation was strong. When asked about learning, the most
      frequent responses were topic-related. At this stage of dental education, the
      students were largely focused on their future practice and found it easier to
      connect to an imagined future than a past experience. In terms of student
      abilities to reflect, the majority were skilled at simple reflection, based on
      these essays since only 18% were non-reflective and 15% showed strong critical
      reflection skills. The open and respectful environment of the salons enabled
      discussion and promoted reflection. These results suggest that more opportunities
      for collegial conversations and instruction in reflective practice earlier in the
      dental curriculum may be beneficial. 

PMID- 27037456
TI  - Using a Dental Student Exercise on Shear Bond Testing to Both Provide Skills
      Practice and Demonstrate a Research Process.
AB  - This article describes an exercise with junior dental students at the University
      of the Pacific Arthur A. Dugoni School of Dentistry designed in part to serve the
      requirement for dental accreditation Standard 6-3 ("Dental education programs
      must provide opportunities, encourage, and support student participation in
      research and other scholarly activities mentored by faculty"). The exercise has
      been conducted for seven years and has been found to provide a distinctive and
      important experience to the education of these dental students. The exercise has
      three aims. First, it is an exercise in which students practice their skills with
      dental bonding; second, it serves as a tool to give immediate feedback on these
      skills that is otherwise not possible in a real patient situation; and third, it
      demonstrates to the students how data from the exercise with the students as
      subjects can be used in a research study. The project thus serves as an
      innovative way to use a skill-building exercise to educate students about
      research at the same time. 

PMID- 27037458
TI  - Variable Pyrethroid Susceptibility Among the Sweet Corn-Infesting Ulidiidae
      (Diptera) in Florida and New Baseline Susceptibilities.
AB  - Florida sweet corn is intensively treated to prevent infestation from the corn
      infesting picture-winged fly complex (hereafter referred to as silk flies,
      Diptera: Ulidiidae). Previous bioassays performed onEuxesta stigmatiasLoew
      demonstrated some pyrethroids performed weakly, while others were more
      efficacious and with longer-lasting residual activity. Since the last published
      bioassays, new active ingredients have been made available, other species in the
      complex discovered, and label restrictions increased for some products. For these
      reasons, topical bioassays were performed on the three most common species to
      assess insecticide efficacy of current commercial products labeled for either
      silk fly or fall armyworm (Spodoptera frugiperda(J.E. Smith), Lepidoptera:
      Noctuidae) control. Bioassays were conducted using formulated product mixed in
      water and applied using a Generation III Research Spray Booth. The median lethal
      concentration ratio (LC50) of beta-cyfluthrin with and without the pyrethroid
      synergist piperonyl butoxide was investigated. Acetamiprid, chlorantraniliprole,
      carbaryl, and flubendiamide did not result in high mortality to any species
      tested.Euxesta elutaLoew was susceptible to all other insecticides tested, and
      exhibited the lowest LC50to beta-cyfluthrin. BothChaetopsis massylaWalker andE.
      stigmatiasrecovered from several pyrethroid treatments.Euxesta stigmatiasalso had
      the highest beta-cyfluthrin LC50, and piperonyl butoxide restored beta-cyfluthrin
      efficacy and lowered the LC50s of all three species.

PMID- 27037459
TI  - Age and fertility: a social-biologic balance.

PMID- 27037460
TI  - Combination of metabolism measurement and a time-lapse system provides an embryo
      selection method based on oxygen uptake and chronology of cytokinesis timing.
AB  - OBJECTIVE: To evaluate correlations between oxygen consumption (OC) measurements
      before and after embryo cytokinesis, observing OC during embryo cleavages and
      combining that information with morphokinetics to relate to implantation
      potential. DESIGN: Prospective cohort study. SETTING: University-affiliated
      private IVF unit. PATIENT(S): A total of 1,150 injected oocytes in 86 first
      oocyte donation cycles with embryo transfer on day 3. INTERVENTION(S): None. MAIN
      OUTCOME MEASUREMENT(S): We analyzed the embryo OC and combined this data with the
      cytokinesis event, exact timing (in hours) of blastomeric cleavages, with the use
      of an incubator equipped with time-lapse videography, gathering a total of 7,630
      measurements during the cytokinesis (active phase) and consecutive measurements
      after this division (passive phase), correlating this data with embryo outcome.
      RESULT(S): OC was found to increase during embryo cleavage, showing high levels
      during first division with a strong correlation with implantation success.
      Moreover, those embryos with slow or fast development gave rise to lower OC
      levels, whereas higher levels were associated with optimal embryo division ranges
      linked to higher implantation potential. CONCLUSION(S): A detailed analysis of OC
      by time-lapse observations enhances the value that these measurements represented
      as markers of embryo quality, especially during the cytokinesis events produced
      during preimplantation development.

PMID- 27037461
TI  - Economic implications of the Society for Assisted Reproductive Technology embryo
      transfer guidelines: healthcare dollars saved by reducing iatrogenic triplets.
AB  - OBJECTIVE: To estimate the national cost savings resulting from reductions in
      higher-order multiple (HOM) live births (defined as three or more fetuses),
      following the initial publication of the Society for Assisted Reproductive
      Technology (SART) guidelines on ET in 1998. DESIGN: Descriptive use and cost
      analysis. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S):
      Not applicable. MAIN OUTCOME MEASURE(S): Estimates of the total number of HOM
      deliveries prevented (from 1998-2012) following the publication of SART
      guidelines; the associated healthcare savings (2014 US dollars). RESULT(S): A
      singleton live birth was estimated to cost $17,100-$24,200. A twin live birth was
      estimated at $66,000-$117,500. A triplet live birth was estimated at $190,800
      $456,300. The percentage of HOM gestations among all ART pregnancies decreased
      from 11.4% in 1997 to 2.0% in 2012, with the sharpest year-over-year decline of
      20.3% occurring in the year following the publication of the guidelines. The
      number of prevented HOM deliveries from 1998 through 2012 was estimated to be
      between 13,500 and 16,300, corresponding to cost savings of $6.02B (billion)
      (range, $2.35B-$7.03B, 2014 US dollars). CONCLUSION(S): Iatrogenic HOM gestations
      represent a substantial economic burden to our healthcare system. The
      introduction of guidelines for ET in 1998 coincided with a dramatic decrease in
      the HOM rate in subsequent years and an associated cumulative cost savings of
      more than $6B. Further reductions in HOM gestations could save up to an
      additional $2B annually.

PMID- 27037462
TI  - Optimal timing of misoprostol administration in nulliparous women undergoing
      office hysteroscopy: a randomized double-blind placebo-controlled study.
AB  - OBJECTIVE: To determine the optimal timing of vaginal misoprostol administration
      in nulliparous women undergoing office hysteroscopy. DESIGN: Randomized double
      blind placebo-controlled study. SETTING: University teaching hospital.
      PATIENT(S): One hundred twenty nulliparous patients were randomly allocated in a
      1:1 ratio to the long-interval misoprostol group or the short-interval
      misoprostol group. INTERVENTION(S): In the long-interval misoprostol group, two
      misoprostol tablets (400 MUg) and two placebo tablets were administered vaginally
      at 12 and 3 hours, respectively, before office hysteroscopy. In the short
      interval misoprostol group, two placebo tablets and two misoprostol tablets (400
      MUg) were administered vaginally 12 and 3 hours, respectively, before office
      hysteroscopy. MAIN OUTCOME MEASURE(S): The severity of pain was assessed by the
      patients with the use of a 100-mm visual analog scale (VAS). The operators
      assessed the ease of the passage of the hysteroscope through the cervical canal
      with the use of a 100-mm VAS as well. RESULT(S): Pain scores during the procedure
      were significantly lower in the long-interval misoprostol group (37.98 +/- 13.13
      vs. 51.98 +/- 20.68). In contrast, the pain scores 30 minutes after the procedure
      were similar between the two groups (11.92 +/- 7.22 vs. 13.3 +/- 6.73). Moreover,
      the passage of the hysteroscope through the cervical canal was easier in the long
      interval misoprostol group (48.9 +/- 17.79 vs. 58.28 +/- 21.85). CONCLUSION(S):
      Vaginal misoprostol administration 12 hours before office hysteroscopy was more
      effective than vaginal misoprostol administration 3 hours before office
      hysteroscopy in relieving pain experienced by nulliparous patients undergoing
      office hysteroscopy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02316301.

PMID- 27037464
TI  - Journal of Dairy Science((r)) 2015 Editorial Report.

PMID- 27037463
TI  - A spherical harmonics intensity model for 3D segmentation and 3D shape analysis
      of heterochromatin foci.
AB  - The genome is partitioned into regions of euchromatin and heterochromatin. The
      organization of heterochromatin is important for the regulation of cellular
      processes such as chromosome segregation and gene silencing, and their
      misregulation is linked to cancer and other diseases. We present a model-based
      approach for automatic 3D segmentation and 3D shape analysis of heterochromatin
      foci from 3D confocal light microscopy images. Our approach employs a novel 3D
      intensity model based on spherical harmonics, which analytically describes the
      shape and intensities of the foci. The model parameters are determined by fitting
      the model to the image intensities using least-squares minimization. To
      characterize the 3D shape of the foci, we exploit the computed spherical
      harmonics coefficients and determine a shape descriptor. We applied our approach
      to 3D synthetic image data as well as real 3D static and real 3D time-lapse
      microscopy images, and compared the performance with that of previous approaches.
      It turned out that our approach yields accurate 3D segmentation results and
      performs better than previous approaches. We also show that our approach can be
      used for quantifying 3D shape differences of heterochromatin foci.

PMID- 27037465
TI  - Letter to the Editor: Comments on Journal of Dairy Science statistical unit
      policy as it relates to pen-based animal studies.

PMID- 27037466
TI  - Letter to the Editor: A Response to Robinson (2016).

PMID- 27037467
TI  - Genomic selection for tolerance to heat stress in Australian dairy cattle.
AB  - Temperature and humidity levels above a certain threshold decrease milk
      production in dairy cattle, and genetic variation is associated with the amount
      of lost production. To enable selection for improved heat tolerance, the aim of
      this study was to develop genomic estimated breeding values (GEBV) for heat
      tolerance in dairy cattle. Heat tolerance was defined as the rate of decline in
      production under heat stress. We combined herd test-day recording data from
      366,835 Holstein and 76,852 Jersey cows with daily temperature and humidity
      measurements from weather stations closest to the tested herds for test days
      between 2003 and 2013. We used daily mean values of temperature-humidity index
      averaged for the day of test and the 4 previous days as the measure of heat
      stress. Tolerance to heat stress was estimated for each cow using a random
      regression model with a common threshold of temperature-humidity index=60 for all
      cows. The slope solutions for cows from this model were used to define the
      daughter trait deviations of their sires. Genomic best linear unbiased prediction
      was used to calculate GEBV for heat tolerance for milk, fat, and protein yield.
      Two reference populations were used, the first consisted of genotyped sires only
      (2,300 Holstein and 575 Jersey sires), and the other included genotyped sires and
      cows (2,189 Holstein and 1,188 Jersey cows). The remainder of the genotyped sires
      were used as a validation set. All animals had genotypes for 632,003 single
      nucleotide polymorphisms. When using only genotyped sires in the reference set
      and only the first parity data, the accuracy of GEBV for heat tolerance in
      relation to changes in milk, fat, and protein yield were 0.48, 0.50, and 0.49 in
      the Holstein validation sires and 0.44, 0.61, and 0.53 in the Jersey validation
      sires, respectively. Some slight improvement in the accuracy of prediction was
      achieved when cows were included in the reference population for Holsteins. No
      clear improvements in the accuracy of genomic prediction were observed when data
      from the second and third parities were included. Correlations of GEBV for heat
      tolerance with Australian Breeding Values for other traits suggested heat
      tolerance had a favorable genetic correlation with fertility (0.29-0.39 in
      Holsteins and 0.15-0.27 in Jerseys), but unfavorable correlations for some
      production traits. Options to improve heat tolerance with genomic selection in
      Australian dairy cattle are discussed. 

PMID- 27037468
TI  - Corrigendum to "Nonambulatory cows: Duration of recumbency and quality of nursing
      care affect outcome of flotation therapy" (J. Dairy Sci. 99:2076-2085).

PMID- 27037469
TI  - Bioremediation of polychlorinated-p-dioxins/dibenzofurans contaminated soil using
      simulated compost-amended landfill reactors under hypoxic conditions.
AB  - Compost-amended landfill reactors were developed to reduce polychlorinated-p
      dioxins and dibenzofurans (PCDD/Fs) in contaminated soils. By periodically
      recirculating leachate and suppling oxygen, the online monitoring of the
      oxidation reduction potential confirmed that the reactors were maintained under
      hypoxic conditions, with redox levels constantly fluctuating between -400 and
      +80mV. The subsequent reactor operation demonstrated that PCDD/F degradation in
      soil could be facilitated by amending compost originating from the cow manure and
      waste sludge and that the degradation might be affected by the availability of
      easily degradable substrates in the soil and compost. The pyrosequencing analysis
      of V4/V5 regions of bacterial 16S rRNA genes suggested that species richness of
      the soil microbial community was increased by a factor of 1.37-1.61. Although the
      bacterial community varied with the compost origin and changed markedly during
      reactor operation, it was dominated by Alphaproteobacteria, Gammaproteobacteria,
      Actinobacteria, and Firmicutes. The aerotolerant anaerobic Sedimentibacter and
      Propionibacterium spp., and the uncultured Chloroflexi group could be temporarily
      induced to a high abundance by amending the cow manure compost; the bacterial
      growths were associated with the rapid degradation of PCDD/Fs. Overall, the novel
      bioremediation method for PCDD/F-contaminated soils using hypoxic conditions was
      effective, simple, energy saving, and thus easily practicable.

PMID- 27037470
TI  - The toxicity, bioaccumulation, elimination, conversion of the enantiomers of
      fipronil in Anodonta woodiana.
AB  - The enantioselective bioaccumulation and elimination of fipronil in Anodonta
      woodiana (A. woodiana) were studied and the main metabolites fipronil desulfinyl,
      fipronil sulfide and fipronil sulfone were determined. The acute toxicity of the
      enantiomers of fipronil and the three metabolites were also investigated. In the
      bioaccumulation process, fipronil in A. woodiana reached equilibrium after 11days
      with BCF value of 0.2, and the enantiomeric fraction (EF) values showed that the
      bioaccumulation was enantioselective with enantioenrichment of S-fipronil. The
      degradation of fipronil in A. woodiana fitted first-order kinetics model with
      half-lives of the enantiomers were 5.8 d for R-fipronil and 7.6 d for S-fipronil,
      and the EF values decreasing from 0.5 gradually indicating the R-enantiomer was
      preferentially degraded. The degradation of single enantiomers was also performed
      and the results revealed a fast conversion of R-fipronil to S-fipronil by A.
      woodiana. The three metabolites were all detected in A. woodiana-water system, in
      which fipronil sulfone and fipronil sulfide had higher concentration levels.
      According to the 72-h LC50 values, S-fipronil was much more toxic than the
      racemate and R-fipronil. Moreover, the metabolites were more toxic than the
      parent fipronil. The results suggested the individual enantiomers of chiral
      pollutants and the metabolites should be considered in the risk assessments.

PMID- 27037471
TI  - Combination of complex adsorption and anammox for nitric oxide removal.
AB  - High-efficiency Fe(II)EDTA (approximately 80%) was selected to remove nitric
      oxide (NO) in a complex adsorption process; subsequently, this Fe(II)EDTA was
      combined with the anammox process to eliminate the NO in flue gas. The Fe(II)EDTA
      NO solution negatively affected the conventional nitrite-dependent anammox
      bacteria when the solution concentration exceeded 0.5mM. Fe(II)EDTA-NO-cultivated
      anammox bacteria removed the ammonium coupled to complex NO reduction (<=3.5mM).
      The batch test results demonstrated that NH4(+) was eliminated through Fe(II)EDTA
      NO reduction via anammox. The removal of complex NO and NH4(+) exhibited high
      relativity relevance, and the Fe(II)EDTA-NO/NH4(+) molar ratio was approximately
      0.97. The complex NO-dependent process generates lesser nitrate than that
      generated by conventional anammox. Moreover, Candidatus Kuenenia
      stuttgartiensitiensis became the dominant anammox bacterial community when the
      biomass is cultivated using the inoculated bacteria, and the proportion of the
      former increased to 90% from the initial 38% for ribosomal intergenic spacer
      analysis and library construction.

PMID- 27037472
TI  - Degradation of atrazine by a novel Fenton-like process and assessment the
      influence on the treated soil.
AB  - This is the premier study reporting the remediation of atrazine contaminated soil
      with steel converter slag (SCS) catalyzed Fenton-like process. The effects of
      various operating parameters, such as SCS loads and H2O2 concentrations were
      evaluated with respect to the removal efficiency of atrazine. Results show the
      optimal SCS load and H2O2 concentration were 80gkg(-1) and 10%, respectably. The
      graded modified Fenton's oxidation with a 3-time addition of 10% H2O2 was able to
      remove 93.7% of total atrazine in the contaminated soil and maintain soil
      temperature within 50 degrees C. In contrast to traditional Fenton treatment, a
      slight pH increase has been observed due to the addition of SCS. More
      importantly, experiment conducted at natural conditions with SCS gave the similar
      atrazine removal to the experiments with the other catalysts (e.g., FeSO4 and
      Fe2O3). One thing should be noted that after the treatment, dissolved organic
      carbon (DOC) content increased to 1.206gkg(-1) from an initial value of 0.339gkg(
      1).

PMID- 27037473
TI  - Integrated adsorptive technique for efficient recovery of m-cresol and m
      toluidine from actual acidic and salty wastewater.
AB  - An integrated adsorptive technique combining an m-cresol adsorption unit, an acid
      retardation unit and an m-toluidine adsorption unit in sequence was designed to
      recover m-cresol and m-toluidine from highly acidic and salty m-cresol
      manufacturing wastewater. In the first column packed with hypercrosslinked
      polymeric resin (NDA-99), most m-cresol was captured through pi-pi and hydrogen
      bonding interactions as well as the salting-out effect, while m-toluidine was not
      absorbed due to protonation. To separate acid from salt, an acid retardation unit
      was introduced successively to adsorb sulfuric acid by strong base anion exchange
      resin (201*7). After the acid retardation unit and mild neutralization reaction,
      the last column filled with NDA-99 was applied to trap neutral m-toluidine from
      the salty effluent. Moreover, the eluent of the acid retardation unit was
      utilized as the regenerant to recover m-toluidine, and the recycled high-acidity
      and low-salinity solution of m-toluidine was directly used to produce m-cresol as
      the raw material. Therefore, the proposed method not only efficiently recycled m
      cresol and m-toluidine, but also reduced the consumption of alkali dramatically
      (saving 0.1628t/t wastewater). These findings will inspire design of integrated
      adsorptive techniques for treating complex organic wastewater with high
      efficiency and low cost.

PMID- 27037474
TI  - Physico-chemical properties and toxicity of alkylated polycyclic aromatic
      hydrocarbons.
AB  - Crude oil and refined petroleum products contain many polycyclic and heterocyclic
      aromatic hydrocarbons, in particular, alkylated PAHs. Although alkylated PAHs are
      found in significantly higher quantities than their corresponding unsubstituted
      PAHs, the most studies on the physico-chemical properties and toxicities of these
      compounds have been conducted on unsubstituted PAHs. In this study, we measured
      crucial physico-chemical properties (i.e., water solubility, partition
      coefficients between polydimethylsiloxane and water (KPDMSw), and partition
      coefficient between liposomes and water (Klipw)) of selected alkylated PAHs, and
      evaluated their toxicity using the luminescence inhibition of Aliivibrio fischeri
      and growth inhibition of Raphidocelis subcapitata. In general, the logarithms of
      these properties for alkylated PAHs showed good linear correlations with log Kow,
      as did those for unsubstituted PAHs. Changes in molecular symmetry on the
      introduction of alkyl groups on aromatic ring structure significantly altered
      water solubility. The inhibition of bacterial luminescence and algal growth by
      alkylated PAHs can be explained well by the baseline toxicity hypothesis, and
      good linear relationships between log Kow or log Klipw and log (1/EC50) were
      found.

PMID- 27037475
TI  - Electro-removal of arsenic(III) and arsenic(V) from aqueous solutions by
      capacitive deionization.
AB  - The feasibility of the electro-removal of arsenate (As(V)) and arsenite (As(III))
      from aqueous solutions via capacitive deionization was investigated. The effects
      of applied voltage (0.0-1.2V) and initial concentration (0.1-200mgL(-1)) on
      arsenic removal were examined. As evidenced, an enhancement of arsenic removal
      can be achieved by capacitive deionization. The capacity to remove As(V) at an
      initial concentration of 0.2mgL(-1) on the activated carbon electrode at 1.2V was
      determined to be 2.47*10(-2)mgg(-1), which is 1.8-fold higher than that of
      As(III) (1.37*10(-2)mgg(-1)). Notably, the possible transformation of arsenic
      species was further characterized. The higher effectiveness of As(V) removal via
      electrosorption at 1.2V was attributed to the formation of an electrical double
      layer at the electrode/solution interface. The removal of As(III) could be
      achieved by the oxidation of As(III) to As(V) and subsequent electrosorption of
      the As(V) onto the electrode surface of the anode. The presence of sodium
      chloride or natural organic matter was found to considerably decrease arsenic
      removal. Single-pass electrosorption-desorption experiments conducted at 1.2V
      further demonstrated that capacitive deionization is a potential means of
      effectively removing arsenic from aqueous solutions.

PMID- 27037476
TI  - Effects of carbonaceous materials on microbial bioavailability of 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47) in sediments.
AB  - In this study, we investigated the influence of various types of carbonaceous
      materials (CMs) on the bioavailability of 2,2',4,4'-tetrabromodiphenyl ether (BDE
      47) to polybrominated diphenyl ether (PBDE)-degrading microorganisms in CM
      amended sediments. The microbial debromination ratio of BDE-47 was reduced by
      92.8%-98.2% in the 5.0% CM-amended sediment compared with in sediment without CM
      amendment after 100 d of anaerobic incubation. The concentrations of lower
      brominated products also decreased when the content of CMs increased from 0.2% to
      5.0%. The inhibitory effects of CMs on BDE-47 debromination were CM content- and
      characteristic-specific. The reciprocals of BDE-47 debromination ratios and lower
      brominated product concentrations showed positive linear correlations with CM
      contents in sediments (p<0.01), and the slopes of linear regression fitting
      generally correlated with specific surface areas (SSAs) of CMs. Desorption of BDE
      47 from CMs indicated the declined desorbing fraction of BDE-47 was responsible
      for the reduction in BDE-47 bioavailability to microorganisms, thus decreasing
      its debromination in sediments amended with CMs. This study revealed that CM
      amendment could reduce the PBDE bioavailability to PBDE-degrading microorganisms
      in sediments, and it is expected to help deepen our understanding of the
      environmental behaviors and risks of PBDEs.

PMID- 27037477
TI  - The impact of functionalized CNT in the network of sodium alginate-based
      nanocomposite beads on the removal of Co(II) ions from aqueous solutions.
AB  - Significant efforts have been made to develop highly efficient adsorbents to
      remove radioactive Co(II) ion pollutants from medical and industrial wastewaters.
      In this study, amide group functionalized multi-walled carbon nanotube (CNT
      CONH2) imprinted in the network of sodium alginate containing hydroxyapatite, and
      new nanocomposite beads were synthesized. Then, they were characterized using
      Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD),
      field emission scanning electron microscopy (FESEM), transmission electron
      microscopy (TEM) and energy dispersive spectroscopy (EDS). The prepared
      nanocomposite beads were used as an adsorbent of Co(II) ions from an aqueous
      solution. The presence and distribution of Co(II) ions in the surface of the
      nanocomposite beads was confirmed using FESEM, EDS and metal mapping analysis.
      The effect of various experimental conditions such as time, pH, and initial
      concentration of the adsorbate solution and temperature on the adsorption
      capacity of the nanocomposite beads were explored. The maximum Co(II) ions
      adsorption capacity of the prepared nanocomposite beads with the largest surface
      area of 163.4m(2)g(-1) was 347.8mgg(-1) in the optimized condition. The
      adsorption mechanism followed a pseudo-second-order kinetic model. Furthermore,
      the Freundlich appears to produce better fit than the Langmuir adsorption
      isotherm. Finally, thermodynamic studies suggest that endothermic adsorption
      process of Co(II) ions is spontaneous and thermodynamically favorable.

PMID- 27037478
TI  - Aging study on carboxymethyl cellulose-coated zero-valent iron nanoparticles in
      water: Chemical transformation and structural evolution.
AB  - To assess the long-term fate and the associated risks of nanoscale zero-valent
      iron (nZVI) used in the water remediation, it is essential to understand the
      chemical transformations during aging of nZVI in water. This study investigated
      the compositional and structural evolution of bare nZVI and carboxymethyl
      cellulose (CMC) coated nZVI in static water over a period of 90 days. Fourier
      transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), X-ray
      diffraction (XRD) and Raman spectroscopy were used to characterize the corrosion
      products of nZVI and CMC-nZVI. Results show that both the structures and the
      compositions of the corrosion products change with the process of aging, but the
      coating of CMC could slow down the aging rate of nZVI (as indicated by the slower
      drop in Fe(0) intensity in XRD pattern). For the bare nZVI, magnetite (Fe3O4)
      and/or maghemite (gamma-Fe2O3) are the dominant corrosion products after 90 days
      of aging. However, for the CMC-nZVI, the core-shell spheres collapses to acicular
      shaped structures after aging with crystalline lepidocrocite (gamma-FeOOH) as the
      primary end product. Moreover, more lepidocrocite present in the corrosion
      products of CMC-nZVI with higher loading of CMC, which reveals that the CMC
      coating could influence the transformation of iron oxides.

PMID- 27037479
TI  - Surface decoration of amine-rich carbon nitride with iron nanoparticles for
      arsenite (As(III)) uptake: The evolution of the Fe-phases under ambient
      conditions.
AB  - A novel hybrid material (gC3N4-rFe) consisting of amine-rich graphitic carbon
      nitride (gC3N4), decorated with reduced iron nanoparticles (rFe) is presented.
      XRD and TEM show that gC3N4-rFe bears aggregation-free Fe-nanoparticles (10nm)
      uniformly dispersed over the gC3N4 surface. In contrast, non-supported iron
      nanoparticles are strongly aggregated, with non-uniform size distribution (20
      100nm). (57)Fe-Mossbauer spectroscopy, dual-mode electron paramagnetic resonance
      (EPR) and magnetization measurements, allow a detailed mapping of the evolution
      of the Fe-phases after exposure to ambient O2. The as-prepared gC3N4-rFe bears
      Fe(2+) and Fe degrees  phases, however only after long exposure to ambient O2, a
      Fe-oxide layer is formed around the Fe degrees  core. In this [Fe degrees /Fe
      oxide] core-shell configuration, the gC3N4-rFe hybrid shows enhanced As(III)
      uptake capacity of 76.5mgg(-1), i.e., ca 90% higher than the unmodified
      carbonaceous support, and 300% higher than the non-supported Fe-nanoparticles.
      gC3N4-rFe is a superior As(III) sorbent i.e., compared to its single counterparts
      or vs. graphite/graphite oxide or activated carbon analogues (11-36mgg(-1)). The
      present results demonstrate that the gC3N4 matrix is not simply a net that holds
      the particles, but rather an active component that determines particle formation
      dynamics and ultimately their redox profile, size and surface dispersion
      homogeneity.

PMID- 27037480
TI  - Local and seasonal variations in concentrations of chlorinated polycyclic
      aromatic hydrocarbons associated with particles in a Japanese megacity.
AB  - Concentrations of particle-bound polycyclic aromatic hydrocarbons (PAHs) and
      chlorinated PAHs (ClPAHs) were measured in different seasons at five sampling
      stations in Nagoya, a Japanese megacity. The annual mean total ClPAH and total
      PAH concentrations were 43.3-92.6pg/m(3) and 5200-8570pg/m(3), respectively. The
      concentrations of total ClPAHs were significantly variable than those of total
      PAHs, and both total concentrations through the seasons did not significantly
      correlate at any of the stations. Principal component analysis was used to
      characterize the ClPAH sources, resulted that ClPAHs were found to be associated
      with the sources of high-molecular-weight PAHs in the warmer seasons and of low
      molecular-weight PAHs in the colder seasons. These findings suggest that
      principal sources of particle-bound ClPAHs are present in the local area, and
      change in the seasons. Toxic equivalent (TEQ) concentrations were estimated to
      assess the risks associated with exposure to ClPAHs in air. The TEQ
      concentrations in the samples were 0.05-0.32pg-TEQ/m(3). The TEQ concentrations
      in summer were approximately half the TEQ concentrations in the other seasons at
      all of the stations.

PMID- 27037481
TI  - Single and multi-component adsorptive removal of bisphenol A and 2,4
      dichlorophenol from aqueous solutions with transition metal modified inorganic
      organic pillared clay composites: Effect of pH and presence of humic acid.
AB  - Pillared clay based composites containing transition metals and a surfactant,
      namely MAlOr-NaBt (Bt=bentonite; Or=surfactant; M=Ni(2+), Cu(2+)or Co(2+)), were
      prepared to study selectivity and capacity toward single and multiple-component
      adsorption of bisphenol A (BPA) and 2,4-diclorophenol (DCP) from water. Tests
      were also performed to account for the presence of natural organic matter in the
      form of humic acid (HA). Equilibrium adsorption capacities for single components
      increased as follows: NaBt<Al-NaBt<AlOr-NaBt<MAlOr-NaBt. The observed equilibrium
      loadings were ca. 5 and 3mgg(-1) for BPA and DCP, respectively, at neutral pH
      conditions and ambient temperature, representing an ordered of magnitude increase
      over the unmodified pillared clay capacities. Inclusion of the transition metal
      brought an increase of nearly two-fold in adsorption capacity over the materials
      modified only with surfactant. The MAlOr-NaBt adsorbents displayed remarkable
      selectivity for BPA. Multi-component fixed-bed tests, however, revealed
      competition between the adsorbates, with the exception of the CuAlOr-NaBt beds.
      Inclusion of HA, surprisingly, enhanced the phenols adsorption capacity.
      Preliminary regeneration tests suggested that the adsorbent capacity can be
      recovered via thermal treatment or by washing with alkaline solutions. The former
      strategy, however, requires surfactant replenishment. More complex schemes would
      be needed to deal with absorbed HA.

PMID- 27037482
TI  - Parental perception of functional status and impact on the family of children
      with congenital heart surgery.
AB  - AIMS: To assess the functional status and the family impact of children with
      congenital heart defects (CHD), using the parental Functional Status II (FS-II)
      and the Impact on Family (IOF) questionnaires. METHODS: In this prospective
      observational study, parents of children who underwent surgery for CHD during the
      first year of life completed the FS-II and the IOF questionnaires. Genetic
      syndromes and prematurity <32weeks were exclusion criteria. The FS-II generates a
      total score and age specific general health (GH), activity (A) and,
      responsiveness (R) subscales. The IOF generates a total scale and financial and
      sibling subscales. RESULTS: Our cohort (n=100), comprised 54% males; the median
      (IQR) age was 32 (10-56) months. Eighteen children had age-specific scores in the
      1-2 SD below mean range (n=17) or more than 2 SD below the mean (n=1) for "ill
      children". There were significant negative correlations between the total FS-II
      and total IOF (r=-0.35, p<0.001) and financial IOF (r=-0.35, p<0.001). RACHS-1
      category of CHD 4-6 was associated with higher likelihood of lower functional
      status. CONCLUSIONS: More complex CHD was associated with lower functional
      status, which correlated with a greater impact on the families. Parental
      questionnaires may be useful instruments for developmental surveillance in this
      population.

PMID- 27037483
TI  - Habit reversal training and educational group treatments for children with
      tourette syndrome: A preliminary randomised controlled trial.
AB  - Quality of life of children with Tourette Syndrome (TS) is impacted greatly by
      its symptoms and their social consequences. Habit Reversal Training (HRT) is
      effective but has not, until now, been empirically evaluated in groups. This
      randomised controlled trial evaluated feasibility and preliminary efficacy of
      eight HRT group sessions compared to eight Education group sessions. Thirty-three
      children aged 9-13 years with TS or Chronic Tic Disorder took part. Outcomes
      evaluated were tic severity and quality of life (QoL). Tic severity improvements
      were found in both groups. Motor tic severity (Yale Global Tic Severity Scale)
      showed greatest improvements in the HRT group. Both groups showed a strong
      tendency toward improvements in patient reported QoL. In conclusion, group-based
      treatments for TS are feasible and exposure to other children with tics did not
      increase tic expression. HRT led to greater reductions in tic severity than
      Education. Implications, such as cost-effectiveness of treatment delivery, are
      discussed. 

PMID- 27037484
TI  - Once a Utilitarian, Consistently a Utilitarian? Examining Principledness in Moral
      Judgment via the Robustness of Individual Differences.
AB  - Although individual differences in the application of moral principles, such as
      utilitarianism, have been documented, so too have powerful context effects
      effects that raise doubts about the durability of people's moral principles. In
      this article, we examine the robustness of individual differences in moral
      judgment by examining them across time and across different decision contexts. In
      Study 1, consistency in utilitarian judgment of 122 adult participants was
      examined over two different survey sessions. In Studies 2A and 2B, large samples
      (Ns = 130 and 327, respectively) of adult participants made a series of 32 moral
      judgments across eight different contexts that are known to affect utilitarian
      endorsement. Contrary to some contemporary theorizing, our results reveal a
      strong degree of consistency in moral judgment. Across time and experimental
      manipulations of context, individuals maintained their relative standing on
      utilitarianism, and aggregated moral decisions reached levels of near-perfect
      consistency. Results support the view that on at least one dimension
      (utilitarianism), people's moral judgments are robustly consistent, with context
      effects tailoring the application of principles to the particulars of any given
      moral judgment.

PMID- 27037485
TI  - Genetic Mapping.

PMID- 27037486
TI  - An Overview of Biochemical Genetics.
AB  - Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of
      inherited metabolic disorders. While individually rare, the combined incidence of
      these diseases makes them a significant source of morbidity and mortality,
      particularly among infants and young children, and new conditions continue to be
      identified. Inherited metabolic disorders may present as an acute, life
      threatening illness or with more chronic, progressive symptoms. Population-scale
      newborn screening allows for early detection and treatment for >40 different
      metabolic disorders. This introductory unit is intended to provide an overview of
      the different clinical categories of metabolic disorders, including a description
      of modern diagnostic methods and treatment options.

PMID- 27037487
TI  - Quantitative Analysis of Total Plasma Homocysteine by LC-MS/MS.
AB  - Homocysteine is a nonessential, sulfur-containing amino acid involved in one
      carbon (folate) metabolism. A number of inherited and acquired conditions cause
      increased accumulation of this metabolite in blood (homocysteinemia) and other
      biofluids. Homocysteinemia is a risk factor for cardiovascular disease, including
      recurrent thrombosis. Accurate measurement of total plasma homocysteine is an
      important element in the diagnostic evaluation of these disorders. While a number
      of different methods have been developed for this purpose, the focus of this unit
      will be on a specific technique utilizing liquid chromatography-tandem mass
      spectrometry, which provides several advantages in terms of speed, sensitivity,
      and specificity.

PMID- 27037488
TI  - Overview of Clinical Cytogenetics.
AB  - Chromosome analysis is one of the first approaches to genetic testing and remains
      a key component of genetic analysis of constitutional and somatic genetic
      disorders. Numerical or unbalanced structural chromosome abnormalities usually
      lead to multiple congenital anomalies. Sometimes these are compatible with live
      birth, usually resulting in severe cognitive and physical handicaps; other times
      they result in miscarriage or stillbirth. Chromosome rearrangements also occur as
      somatic changes in malignancies. Identification of constitutional chromosomal
      anomalies (anomalies present in most or all cells of the body and/or the
      germline) can provide important information for genetic counseling. In this unit,
      we introduce chromosomal microarray analysis (CMA), which is a relatively recent
      addition to cytogenetic technologies, and has become the recommended first-tier
      testing method for patients with developmental delay, intellectual disability,
      autism, and/or multiple congenital anomalies. We also discuss non-invasive
      prenatal testing/screening (NIPTS), which uses circulating cell-free fetal DNA
      (cfDNA) from maternal plasma to rapidly screen for autosomal and sex-chromosome
      aneuploidies. Cytogenetic analysis of tumors is helpful in diagnosis and in
      monitoring the effects of treatment. The protocols in this chapter cover the
      clinical study of chromosomes in nonmalignant tissues.

PMID- 27037489
TI  - Using ClinVar as a Resource to Support Variant Interpretation.
AB  - ClinVar is a freely accessible, public archive of reports of the relationships
      among genomic variants and phenotypes. To facilitate evaluation of the clinical
      significance of each variant, ClinVar aggregates submissions of the same variant,
      displays supporting data from each submission, and determines if the submitted
      clinical interpretations are conflicting or concordant. The unit describes how to
      (1) identify sequence and structural variants of interest in ClinVar by multiple
      searching approaches, including Variation Viewer and (2) understand the display
      of submissions to ClinVar and the evidence supporting each interpretation. By
      following this protocol, ClinVar users will be able to learn how to incorporate
      the wealth of resources and knowledge in ClinVar into variant curation and
      interpretation.

PMID- 27037490
TI  - Reporting of Diagnostic Cytogenetic Results.
AB  - This appendix, developed by the staff at the Center for Advanced Molecular
      Diagnostics in the Department of Pathology at the Brigham and Women's Hospital,
      includes a comprehensive list of current "macros" or standardized statements used
      to facilitate reporting of cytogenetic results. These are provided as a useful
      reference for other laboratories. The statements are organized under the general
      categories of constitutional or acquired abnormalities and subdivided into
      analysis type (GTG-banding, FISH, or chromosomal microarray). Multi-specimen
      usage macros are included that can be applied to two or more specimen types.

PMID- 27037491
TI  - The effect of relational continuity of care in maternity and child health clinics
      on parenting self-efficacy of mothers and fathers with loneliness and depressive
      symptoms.
AB  - This study explored the parenting self-efficacy of the parents of 18-month-old
      children in the context of Finnish maternity and child health clinics. This
      parenting self-efficacy was observed in relation with the relational continuity
      of care and parents' experienced loneliness and depressive symptoms. The
      relational continuity of care was provided by a public health nurse in maternity
      and child health clinics. The participating parents were drawn from the STEPS
      study that is being carried out by the Institute for Child and Youth Research at
      the University of Turku. The results showed that relational continuity of care
      provided by the same public health nurse in the maternity and child health
      clinics was associated with mothers' higher emotional loneliness and with lower
      scores on three dimensions of parents' parenting self-efficacy. Loneliness and
      depressive symptoms negatively influenced parents' parenting self-efficacy -
      however, in the case where the family had experienced relational continuity of
      care, the parents' higher levels of depressive symptoms had not weakened their
      parenting self-efficacy beliefs. These results are discussed in terms of
      organizing maternity and child health clinic services. 

PMID- 27037492
TI  - Characterization of neuromuscular synapse function abnormalities in multiple
      Duchenne muscular dystrophy mouse models.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked myopathy caused by dystrophin
      deficiency. Dystrophin is present intracellularly at the sarcolemma, connecting
      actin to the dystrophin-associated glycoprotein complex. Interestingly, it is
      enriched postsynaptically at the neuromuscular junction (NMJ), but its synaptic
      function is largely unknown. Utrophin, a dystrophin homologue, is also
      concentrated at the NMJ, and upregulated in DMD. It is possible that the absence
      of dystrophin at NMJs in DMD causes neuromuscular transmission defects that
      aggravate muscle weakness. We studied NMJ function in mdx mice (lacking
      dystrophin) and wild type mice. In addition, mdx/utrn(+/-) and mdx/utrn(-/-) mice
      (lacking utrophin) were used to investigate influences of utrophin levels. The
      three Duchenne mouse models showed muscle weakness when comparatively tested in
      vivo, with mdx/utrn(-/-) mice being weakest. Ex vivo muscle contraction and
      electrophysiological studies showed a reduced safety factor of neuromuscular
      transmission in all models. NMJs had ~ 40% smaller miniature endplate potential
      amplitudes compared with wild type, indicating postsynaptic sensitivity loss for
      the neurotransmitter acetylcholine. However, nerve stimulation-evoked endplate
      potential amplitudes were unchanged. Consequently, quantal content (i.e. the
      number of acetylcholine quanta released per nerve impulse) was considerably
      increased. Such a homeostatic compensatory increase in neurotransmitter release
      is also found at NMJs in myasthenia gravis, where autoantibodies reduce
      acetylcholine receptors. However, high-rate nerve stimulation induced exaggerated
      endplate potential rundown. Study of NMJ morphology showed that fragmentation of
      acetylcholine receptor clusters occurred in all models, being most severe in
      mdx/utrn(-/-) mice. Overall, we showed mild 'myasthenia-like' neuromuscular
      synaptic dysfunction in several Duchenne mouse models, which possibly affects
      muscle weakness and degeneration.

PMID- 27037493
TI  - The ICF as a measure of effectiveness: structure, function, and contextual
      factors.

PMID- 27037494
TI  - Robust risk prediction with biomarkers under two-phase stratified cohort design.
AB  - Identification of novel biomarkers for risk prediction is important for disease
      prevention and optimal treatment selection. However, studies aiming to discover
      which biomarkers are useful for risk prediction often require the use of stored
      biological samples from large assembled cohorts, and thus the depletion of a
      finite and precious resource. To make efficient use of such stored samples, two
      phase sampling designs are often adopted as resource-efficient sampling
      strategies, especially when the outcome of interest is rare. Existing methods for
      analyzing data from two-phase studies focus primarily on single marker analysis
      or fitting the Cox regression model to combine information from multiple markers.
      However, the Cox model may not fit the data well. Under model misspecification,
      the composite score derived from the Cox model may not perform well in predicting
      the outcome. Under a general two-phase stratified cohort sampling design, we
      present a novel approach to combining multiple markers to optimize prediction by
      fitting a flexible nonparametric transformation model. Using inverse probability
      weighting to account for the outcome-dependent sampling, we propose to estimate
      the model parameters by maximizing an objective function which can be interpreted
      as a weighted C-statistic for survival outcomes. Regardless of model adequacy,
      the proposed procedure yields a sensible composite risk score for prediction. A
      major obstacle for making inference under two phase studies is due to the
      correlation induced by the finite population sampling, which prevents standard
      inference procedures such as the bootstrap from being used for variance
      estimation. We propose a resampling procedure to derive valid confidence
      intervals for the model parameters and the C-statistic accuracy measure. We
      illustrate the new methods with simulation studies and an analysis of a two-phase
      study of high-density lipoprotein cholesterol (HDL-C) subtypes for predicting the
      risk of coronary heart disease.

PMID- 27037495
TI  - Role of enteroendocrine L-cells in arginine vasopressin-mediated inhibition of
      colonic anion secretion.
AB  - KEY POINTS: Arginine vasopressin (AVP) stimulates the release of enteroendocrine
      L-cell derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) in
      vitro from mouse and human colons. This is mediated by the AVP receptor 1B, which
      is highly enriched in colonic L-cells and linked to the elevation of L-cell
      calcium and cAMP concentrations. By means of Ussing chambers, we show that AVP
      reduced colonic anion secretion, although this was blocked by a specific
      neuropeptide Y receptor Y1 receptor antagonist, suggesting that L-cell-released
      PYY acts locally on the epithelium to modulate fluid balance. In human serum
      samples, PYY concentrations were higher in samples with raised osmolality and
      copeptin (surrogate marker for AVP). These findings describe, for the first time,
      the role of L-cells in AVP regulated intestinal fluid secretion, potentially
      linking together hormonal control of blood volume and blood glucose levels, and
      thus adding to our understanding of the complex pathways involved in the gut
      hormonal response to different stimuli. ABSTRACT: Arginine vasopressin (AVP)
      regulates fluid balance and blood pressure via AVP receptor (AVPR)2 in the kidney
      and AVP receptor 1A in vascular smooth muscle. Its role in intestinal function
      has received less attention. We hypothesized that enteroendocrine L-cells
      producing glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) may be a target of
      AVP and contribute to the control of fluid balance. Avpr1b expression was
      assessed by quantitative RT-PCR on flourescence-activated cell sorting-isolated L
      and control cells and was enriched in colonic L-cells. AVP stimulated GLP-1 and
      PYY release from primary cultured murine and human colonic cells and was
      associated with elevated calcium and cAMP concentrations in L-cells as measured
      in cultures from GLU-Cre/ROSA26-GCaMP3 and GLU-Epac2camps mice. An antagonist of
      AVPR1B reduced AVP-triggered hormone secretion from murine and human cells. In
      Ussing chambers, basolaterally applied AVP reduced colonic anion secretion and
      this effect was blocked by a specific neuropeptide Y receptor Y1 (NPY1R)
      antagonist. In human serum, PYY concentrations were higher in samples with raised
      osmolality or copeptin (a surrogate marker for AVP). In conclusion, we propose
      that AVP activates L-cell AVPR1B, causing GLP-1 and PYY secretion. PYY in turn
      reduces colonic anion secretion via epithelial NPY1R. Our data suggest L-cells
      are active players in the hypothalamic control of intestinal fluid homeostasis,
      providing a potential link between the regulation of blood
      volume/pressure/osmolality and blood glucose.

PMID- 27037496
TI  - The embodiment of beauty: Evidence from viewing Chinese concrete words and
      pictographs.
AB  - How is beauty embodied? According to the viewpoint of embodied cognition, the
      aesthetic processing of words or pictographs has roots in their referential
      archetypes. Four experiments tested whether the beauty of referential archetypes
      was routinely activated during the explicit and implicit aesthetic evaluations of
      the font structures of concrete Chinese words and pictographs in congruent or
      incongruent font colour. Results showed font structures of simplified Chinese
      words and pictographs were judged to be more beautiful when they referred to
      beautiful archetypes; and this pattern was reversed when they referred to ugly
      archetypes. Moreover, judgement was facilitated when font colour was congruent
      for Chinese words and pictographs referred to beautiful archetypes. For those
      referred to ugly archetypes, judgement was inhibited in congruent font colour but
      facilitated in incongruent font colour, suggesting aesthetic perceptions of the
      font structures of Chinese words and pictographs were derived from their
      referential natural objects. The spontaneous generation hypothesis of beauty is
      proposed to account for these findings.

PMID- 27037497
TI  - Obesity paradox in advanced liver disease: obesity is associated with lower
      mortality in hospitalized patients with cirrhosis.
AB  - BACKGROUND & AIMS: To investigate how obesity impacts inpatient mortality, length
      of stay (LOS) and costs in patients with cirrhosis. Obesity is a growing epidemic
      associated with multiple co-morbidities, increased morbidity, and a significant
      economic burden on healthcare. Despite the overall harmful impact of obesity, the
      'obesity paradox' has been described as decreased mortality among obese vs non
      obese patients in various chronic medical conditions. METHODS: Analysis of the
      Nationwide Inpatient Sample (NIS) for 2012, which contains data from 44 states
      and 4378 hospitals. Data from all cases with primary, secondary or tertiary
      discharge diagnosis of cirrhosis identified by International Classification of
      Diseases-9 code 571.2, 571.5 571.6 were included. Primary outcomes included
      inpatient mortality, LOS, and hospital charges. Obesity as a predictor of
      mortality was defined by a predetermined obesity co-morbidity variable. RESULTS:
      A total of 32,605 patients were included. Crude mortality was lower for obese
      cirrhotic patients (2.7% vs 3.5%, P = 0.02) than for non-obese cirrhotic
      patients. In contrast, median LOS was longer (4 vs 3 days, P < 0.001) and median
      hospital charges were higher for obese cirrhotic patients ($26 803 vs $23 447, P
      < 0.001) In multivariate logistic regression, obesity was associated with a lower
      risk of inpatient mortality (OR=0.73, 95%CI: 0.55-0.95, P = 0.02). CONCLUSIONS:
      In the acute care setting, obese patients with cirrhosis have lower mortality
      than non-obese patients with cirrhosis, longer hospitalizations and higher
      healthcare cost, providing new evidence for the obesity paradox in cirrhosis.
      Obese cirrhotic patients are more likely to have enhanced nutritional reserve
      which may play a role in survival during acute illness.

PMID- 27037498
TI  - Understanding N-Acetyl-L-Glutamate Synthase Deficiency: Mutational Spectrum,
      Impact of Clinical Mutations on Enzyme Functionality, and Structural
      Considerations.
AB  - N-acetyl-L-glutamate synthase (NAGS) deficiency (NAGSD), the rarest urea cycle
      defect, is clinically indistinguishable from carbamoyl phosphate synthetase 1
      deficiency, rendering the identification of NAGS gene mutations key for
      differentiation, which is crucial, as only NAGSD has substitutive therapy. Over
      the last 13 years, we have identified 43 patients from 33 families with NAGS
      mutations, of which 14 were novel. Overall, 36 NAGS mutations have been found so
      far in 56 patients from 42 families, of which 76% are homozygous for the mutant
      allele. 61% of mutations are missense changes. Lack or decrease of NAGS protein
      is predicted for ~1/3 of mutations. Missense mutations frequency is inhomogeneous
      along NAGS: null for exon 1, but six in exon 6, which reflects the paramount
      substrate binding/catalytic role of the C-terminal domain (GNAT domain).
      Correspondingly, phenotypes associated with missense mutations mapping in the
      GNAT domain are more severe than phenotypes of amino acid kinase domain-mapping
      missense mutations. Enzyme activity and stability assays with 12 mutations
      introduced into pure recombinant Pseudomonas aeruginosa NAGS, together with in
      silico structural analysis, support the pathogenic role of most NAGSD-associated
      mutations found. The disease-causing mechanisms appear to be, from higher to
      lower frequency, decreased solubility/stability, aberrant kinetics/catalysis, and
      altered arginine modulation.

PMID- 27037499
TI  - The incidence of calorie labeling on fast food choices: A comparison between
      stated preferences and actual choices.
AB  - In order to test the effect of calorie information on fast food choices, we
      conducted a questionnaire employing two types of stated preferences methods (the
      best-worst-scaling and intentional questions) and a follow-up randomized field
      experiment in a sample of 119 participants. This combined approach allowed us to
      test the internal validity of preferences for fast food meals across elicitation
      scenarios. The results showed that calorie information reduces the probability of
      selecting high calorie meals only in the questionnaire, while it did not have any
      significant impact on actual purchasing behavior in the field experiment. Thus,
      the findings show that there is a clear difference between the role of calorie
      information on immediate stated preference choices, and the relatively low level
      of responsiveness in real choices in a restaurant. We believe that the current
      results are quite suggestive, indicating the limits of predicting actual fast
      food behavior, and may open the way to using data sources that combine stated
      methods with field experiments.

PMID- 27037500
TI  - The self-medication hypothesis: Evidence from terrorism and cigarette
      accessibility.
AB  - We use single equation and system instrumental variable models to explore if
      individuals smoke during times of stress (the motivation effect) and if they are
      successful in self-medicating short-term stress (the self-medication effect).
      Short-term stress is a powerful motivator of smoking, and the decision to smoke
      could trigger biological feedback that immediately reduces short-term stress. We
      use data on self-reported smoking and stress from 240,388 current and former
      smokers. We instrument short-term stress with temporal distance from September
      11, 2001 (using date of interview). We instrument smoking with cigarette
      accessibility measures of cigarette price changes and distance to state borders.
      In the absence of accounting for endogeneity, we find that smoking is associated
      with increases in short-term stress. However, when we account for endogeneity we
      find no evidence of smoking affecting short-term stress. We do find a consistent
      positive effect of short-term stress on smoking.

PMID- 27037501
TI  - Evaluation of TagSeq, a reliable low-cost alternative for RNAseq.
AB  - RNAseq is a relatively new tool for ecological genetics that offers researchers
      insight into changes in gene expression in response to a myriad of natural or
      experimental conditions. However, standard RNAseq methods (e.g., Illumina
      TruSeq(r) or NEBNext(r) ) can be cost prohibitive, especially when study designs
      require large sample sizes. Consequently, RNAseq is often underused as a method,
      or is applied to small sample sizes that confer poor statistical power. Low cost
      RNAseq methods could therefore enable far greater and more powerful applications
      of transcriptomics in ecological genetics and beyond. Standard mRNAseq is costly
      partly because one sequences portions of the full length of all transcripts. Such
      whole-mRNA data are redundant for estimates of relative gene expression. TagSeq
      is an alternative method that focuses sequencing effort on mRNAs' 3' end,
      reducing the necessary sequencing depth per sample, and thus cost. We present a
      revised TagSeq library construction procedure, and compare its performance
      against NEBNext(r) , the 'gold-standard' whole mRNAseq method. We built both
      TagSeq and NEBNext(r) libraries from the same biological samples, each spiked
      with control RNAs. We found that TagSeq measured the control RNA distribution
      more accurately than NEBNext(r) , for a fraction of the cost per sample (~10%).
      The higher accuracy of TagSeq was particularly apparent for transcripts of
      moderate to low abundance. Technical replicates of TagSeq libraries are highly
      correlated, and were correlated with NEBNext(r) results. Overall, we show that
      our modified TagSeq protocol is an efficient alternative to traditional whole
      mRNAseq, offering researchers comparable data at greatly reduced cost.

PMID- 27037502
TI  - Pathological characterization and morphometric analysis of hepatic lesions in
      SHRSP5/Dmcr, an experimental non-alcoholic steatohepatitis model, induced by high
      fat and high-cholesterol diet.
AB  - SHRSP5/Dmcr is a newly established substrain of stroke-prone spontaneously
      hypertensive rat (SHRSP). Recently, high-fat and high-cholesterol (HFC) diet-fed
      SHRSP5/Dmcr has been reported as a novel rat model of developing hepatic lesions
      similar to human non-alcoholic steatohepatitis (NASH). The aim of this study was
      to investigate the detailed pathological conditions induced by HFC diet in
      SHRSP5/Dmcr rats using molecular biological methods and morphometric analysis.
      SHRSP5/Dmcr rats at 6 weeks of age were fed on either HFC diet or stroke-prone
      (SP) diet for 2, 4, 6, 8 and 16 weeks and histopathological changes in the liver,
      blood chemistry and mRNA expression levels in the liver were investigated. As
      evidenced by the histopathological examination of the liver of the SHRSP5/Dmcr
      rats, hepatic steatosis and lobular inflammation were present, with gradual
      increasing severity from 2 weeks after the introduction of the HFC diet. Partial
      hepatic fibrosis was detected at 6 weeks and spread over the entire region of the
      liver with more severe bridging formation by 16 weeks. The degrees of NASH-like
      hepatic lesions such as steatosis (the size distribution of lipid droplets),
      inflammation and fibrosis were quantified by morphometric analysis. Eosinophilic
      inclusion bodies encountered in the hepatocytes had immunoreactivity with Cox-4
      and double-membrane walls, identified as mega-mitochondria. Serum ALT and
      bilirubins, and the mRNA expression levels related to fibrosis were closely
      correlated with hepatic histopathological changes. The clear feeding time
      dependent progression of NASH-like hepatic lesion in HFC diet-fed SHRSP5/Dmcr
      rats reinforced the conclusion that this strain might be a useful model of NASH
      and of inflammatory fibrotic liver disease.

PMID- 27037503
TI  - Ipsilateral cortical inputs to the rostral and caudal motor areas in rats.
AB  - Rats have a complete body representation in the primary motor cortex (M1).
      Rostrally there are additional representations of the forelimb and whiskers,
      called the rostral forelimb area (RFA) and the rostral whisker area (RWA).
      Recently we showed that sources of thalamic inputs to RFA and RWA are similar,
      but they are different from those for the caudal forelimb area (CFA) and the
      caudal whisker area (CWA) of M1 (Mohammed and Jain [2014] J Comp Neurol 522:528
      545). We proposed that RWA and RFA are part of a second motor area, the rostral
      motor area (RMA). Here we report ipsilateral cortical connections of whisker
      representation in RMA, and compare them with connections of CWA. Connections of
      RFA, CFA, and the caudally located hindlimb area (CHA), which is a part of M1,
      were determined for comparison. The most distinctive features of cortical inputs
      to RWA compared with CWA include lack of inputs from the face region of the
      primary somatosensory cortex (S1), and only about half as much inputs from S1
      compared with the lateral somatosensory areas S2 (second somatosensory area) and
      the parietal ventral area (PV). A similar pattern of inputs is seen for CFA and
      RFA, with RFA receiving smaller proportion of inputs from the forepaw region of
      S1 compared with CFA, and receiving fewer inputs from S1 compared with those from
      S2. These and other features of the cortical input pattern suggest that RMA has a
      distinct, and more of integrative functional role compared with M1. J. Comp.
      Neurol. 524:3104-3123, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037504
TI  - Unraveling Epitaxial Habits in the NaLnF4 System for Color Multiplexing at the
      Single-Particle Level.
AB  - We report an epitaxial growth technique for scalable production of hybrid sodium
      rare-earth fluoride (NaLnF4 ) microcrystals, including NaYF4 , NaYbF4 , and
      NaLuF4 material systems. The single crystalline nature of the as-synthesized
      products makes them strong upconversion emission. The freedom of combining a
      lanthanide activator (Er(3+) or Tm(3+) ) with a sensitizer (Yb(3+) ) at various
      doping concentrations readily gives access to color multiplexing at the single
      particle level. Our kinetic and thermodynamic investigations on the epitaxial
      growth of core-shell microcrystals using NaLnF4 particle seeds suggest that
      within a certain size regime it is plausible to exert precise control over shell
      thickness and growth orientation under hydrothermal conditions.

PMID- 27037505
TI  - The prevalence and clinical significance of premature ventricular beats in the
      athlete.
AB  - Adolescents and adults with cardiovascular disease who are engaged in sports
      activity have an increased risk of sudden cardiac death (SCD) that is three times
      greater than that of their non-athletic counterparts. Sport acts as a trigger for
      cardiac arrest in the presence of underlying cardiovascular diseases predisposing
      to life-threatening ventricular arrhythmias. Frequent and complex premature
      ventricular beats (PVBs) detected during the cardiovascular screening of the
      athletic population may be a sign of an underlying cardiovascular disease at risk
      of SCD, but are also often recorded in trained athletes without cardiovascular
      abnormalities. Thus, the interpretation of PVBs could represent a clinical
      dilemma, particularly in the athlete. However, while some characteristics of PVBs
      can be considered common and benign, others occur uncommonly in the athletic
      population and raise the suspicion of an underlying cardiovascular disease. This
      review discusses the prevalence and clinical significance of PVBs in the athlete,
      with a focus on exercise-induced PVBs, on the analysis of PVB's morphology at 12
      lead ECG, and on the morphological substrates identified by imaging techniques.
      The implications on eligibility for competitive sports participation are also
      discussed, according to the relevance of PVB detection for disqualifying athletes
      from competitions.

PMID- 27037506
TI  - Hierarchical Bayesian approaches for detecting inconsistency in network meta
      analysis.
AB  - Network meta-analysis (NMA), also known as multiple treatment comparisons, is
      commonly used to incorporate direct and indirect evidence comparing treatments.
      With recent advances in methods and software, Bayesian approaches to NMA have
      become quite popular and allow models of previously unanticipated complexity.
      However, when direct and indirect evidence differ in an NMA, the model is said to
      suffer from inconsistency. Current inconsistency detection in NMA is usually
      based on contrast-based (CB) models; however, this approach has certain
      limitations. In this work, we propose an arm-based random effects model, where we
      detect discrepancy of direct and indirect evidence for comparing two treatments
      using the fixed effects in the model while flagging extreme trials using the
      random effects. We define discrepancy factors to characterize evidence of
      inconsistency for particular treatment comparisons, which is novel in NMA
      research. Our approaches permit users to address issues previously tackled via CB
      models. We compare sources of inconsistency identified by our approach and
      existing loop-based CB methods using real and simulated datasets and demonstrate
      that our methods can offer powerful inconsistency detection. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27037507
TI  - Mitochondrial DNA Copy Number in Spermatozoa of Fertile Stallions.
AB  - Predicting male fertility on non-invasive sperm traits is of big importance to
      human and animal reproduction strategies. Combining the wide range of parameters
      monitored by computer-assisted sperm analysis (CASA) with some molecular traits
      (e.g. mtDNA content) may help to identify markers of the male fertility. The aim
      of this study was to characterize variation in the mtDNA copy number in equine
      sperm and to investigate whether mtDNA content is correlated with quality traits
      of stallion spermatozoa and the age of the male. Ejaculates collected from 53
      fertile stallions were divided into four age groups (3-5, 6-10, 11-14 and >15
      years) and were subjected to a complex investigation including conventional
      analysis, CASA, flow cytometry and mtDNA content (real-time PCR). The mean (+/
      SD) number of mtDNA copies equalled 14 +/- 9 and varied from 3 to 64. Considering
      the great number of sperm parameters monitored in this study, only few of them
      were correlated with the mtDNA content: ejaculate volume (a positive
      correlation), the amplitude of lateral head displacement (ALH; a negative
      correlation) and the high mitochondrial activity index (a negative correlation).
      The stallion age was not correlated with the mtDNA copy number. This study
      provides the first set of data on mtDNA content in equine sperm and confirms
      phenomena previously described for humans and dog on associations between sperm
      mtDNA content and selected motility parameters monitored by the CASA. Basing our
      study on spermatozoa from fertile stallions could however limit the extent of
      detected associations. 

PMID- 27037508
TI  - Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep.
AB  - Although Salvia divinorum is traditionally known as a 'mind-altering' or
      psychoactive herb used, among others things, as a tranquilizer, this property has
      not been validated with regard to its efficacy and safety. The objective of this
      study is to provide evidence for the sedative effects of S. divinorum and
      discriminate the nature of the responsible constituents by examining different
      experimental models. A battery of tests, including the open-field, hole-board,
      exploration cylinder, plus-maze and sodium pentobarbital-induced hypnosis
      potentiation, were used in mice after administration of non-polar, medium polar
      and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic
      analysis in rats receiving an active medium polar extract (10 and 100 mg/kg)
      containing salvinorins was also assessed to study the effects of this plant on
      sleep architecture. All tested extracts produced significant sedative-like
      responses, although those of the medium polar extract were more pronounced in
      mice. The sedative effect of this latter extract, which contains a mixture of
      salvinorins, caused fragmented sleep architecture in rats by diminishing rapid
      eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg.
      Our results provide evidence that S. divinorum exhibits sedative-like depressant
      properties that alter physiological sleep architecture. Copyright (c) 2016 John
      Wiley & Sons, Ltd. 

PMID- 27037509
TI  - Erratum.

PMID- 27037510
TI  - Normalising desistance: contextualising marijuana and cocaine use careers in
      young adults.
AB  - Although there is a vast literature on drug use and addiction, there is little
      work that addresses the long-term use of drugs within the general population. We
      take a more contextual look in examining longitudinal drug use patterns over the
      course of 14 years for a representative sample of young adults in their late
      teens and early twenties in the United States using the National Longitudinal
      Survey of Youth (NLSY). We use a growth trajectory modelling approach for cocaine
      and marijuana users to determine general use careers. Using contextual and life
      course variables, we then estimate a multinomial logistic regression model to
      predict group membership. In addition to establishing general use career groups,
      we ask how well mainstream theories comport with our findings and how the
      different chemical makeup of cocaine and marijuana influence our findings. We
      find four general use career groups: (i) high use/late desistance; (ii) peaked
      use/strong desistance; (iii) low use; and (iv) stable use/gradual desistance. Our
      results suggest similar careers for users of both drugs, with desistance over
      time as the rule for all groups. We also find some support for life-course and
      contextual factors in drug using patterns, but our findings challenge other
      psychological and criminological theories.

PMID- 27037511
TI  - Detection of Treponema pallidum in tears during early neurosyphilis.

PMID- 27037512
TI  - Bioanalysis of antihistamines for clinical or forensic purposes.
AB  - Antihistamines are a class of drugs that inhibit the action of histamine and are
      used to alleviate symptoms associated with allergic reactions, but some of them
      can cause side effects, the most unpleasant and dangerous of which are the
      sedative effects that may hinder important psychological functions and impair
      skilled performance. These side effects could decrease safety in certain common
      and critical tasks, such as driving or operating machinery, leading to accidents.
      Antihistamines can also cause intoxications, sometimes lethal, especially when co
      administered with alcohol or other sedative drugs. Thus, the development of
      analytical methods for their determination in biological fluids is considered to
      be useful for the investigation of clinical and forensic cases. These
      methodologies could also be used for pharmacokinetic studies. Several liquid and
      a few gas chromatographic methods have been developed for the determination of
      antihistamines in biological matrices after proper pretreatment procedures. This
      article reviews the published analytical methodologies that were gathered through
      the search in PubMed database and the recent developments on isolation or
      determination of antihistamines in biological materials. Current trends and
      future perspectives on bioanalysis of antihistamines are also discussed.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037513
TI  - Glacial refugia, recolonization patterns and diversification forces in Alpine
      endemic Megabunus harvestmen.
AB  - The Pleistocene climatic fluctuations had a huge impact on all life forms, and
      various hypotheses regarding the survival of organisms during glacial periods
      have been postulated. In the European Alps, evidence has been found in support of
      refugia outside the ice shield (massifs de refuge) acting as sources for
      postglacial recolonization of inner-Alpine areas. In contrast, evidence for
      survival on nunataks, ice-free areas above the glacier, remains scarce. Here, we
      combine multivariate genetic analyses with ecological niche models (ENMs) through
      multiple timescales to elucidate the history of Alpine Megabunus harvestmen
      throughout the ice ages, a genus that comprises eight high-altitude endemics.
      ENMs suggest two types of refugia throughout the last glacial maximum, inner
      Alpine survival on nunataks for four species and peripheral refugia for further
      four species. In some geographic regions, the patterns of genetic variation are
      consistent with long-distance dispersal out of massifs de refuge, repeatedly
      coupled with geographic parthenogenesis. In other regions, long-term persistence
      in nunataks may dominate the patterns of genetic divergence. Overall, our results
      suggest that glacial cycles contributed to allopatric diversification in Alpine
      Megabunus, both within and at the margins of the ice shield. These findings
      exemplify the power of ENM projections coupled with genetic analyses to identify
      hypotheses about the position and the number of glacial refugia and thus to
      evaluate the role of Pleistocene glaciations in driving species-specific
      responses of recolonization or persistence that may have contributed to observed
      patterns of biodiversity.

PMID- 27037514
TI  - Sexual Selection on male cuticular hydrocarbons via male-male competition and
      female choice.
AB  - Traditional views of sexual selection assumed that male-male competition and
      female mate choice work in harmony, selecting upon the same traits in the same
      direction. However, we now know that this is not always the case and that these
      two mechanisms often impose conflicting selection on male sexual traits.
      Cuticular hydrocarbons (CHCs) have been shown to be linked to both social
      dominance and male attractiveness in several insect species. However, although
      several studies have estimated the strength and form of sexual selection imposed
      on male CHCs by female mate choice, none have established whether these chemical
      traits are also subject to sexual selection via male-male competition. Using a
      multivariate selection analysis, we estimate and compare sexual selection exerted
      by male-male competition and female mate choice on male CHC composition in the
      broad-horned flour beetle Gnatocerus cornutus. We show that male-male competition
      exerts strong linear selection on both overall CHC abundance and body size in
      males, while female mate choice exerts a mixture of linear and nonlinear
      selection, targeting not just the overall amount of CHCs expressed but the
      relative abundance of specific hydrocarbons as well. We discuss the potential
      implications of this antagonistic selection with regard to male reproductive
      success.

PMID- 27037515
TI  - Formation of the circle of Willis during human embryonic development.
AB  - The circle of Willis (CW) is a circulatory anastomosis that supplies blood to the
      brain and adjacent structures. We examined the timing of formation of CW in 20
      Japanese human embryo samples by using 3-dimensional reconstruction of serial
      histological sections. The CW was closed in 1 (n = 6), 2 (n = 8), 2 (n = 3) and 2
      (n = 3) samples at Carnegie stages 20, 21, 22, and 23, respectively. The CW was
      unclosed in 13 samples (unclosed at ACOM alone, 6 samples; ACOM and bilateral P1,
      4; left PCOM and right P1, 1; right PCOM and right P1, 1; ACOM and left PCOM, 1).
      It was difficult to predict whether the circle would close during further
      development, as such variations frequently exist in adults. 

PMID- 27037516
TI  - Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid
      engineered for the selective recognition of unanchored polyubiquitin.
AB  - Unanchored polyubiquitin chains are emerging as important regulators of cellular
      physiology with diverse roles paralleling those of substrate-conjugated
      polyubiquitin. However tools able to discriminate unanchored polyubiquitin chains
      of different isopeptide linkages have not been reported. We describe the design
      of a linker-optimized ubiquitin-binding domain hybrid (t-UBD) containing two
      UBDs, a ZnF-UBP domain in tandem with a linkage-selective UBA domain, which
      exploits avidity effects to afford selective recognition of unanchored Lys48
      linked polyubiquitin chains. Utilizing native MS to quantitatively probe binding
      affinities we confirm cooperative binding of the UBDs within the synthetic
      protein, and desired binding specificity for Lys48-linked ubiquitin dimers.
      Furthermore, MS/MS analyses indicate that the t-UBD, when applied as an affinity
      enrichment reagent, can be used to favor the purification of endogenous
      unanchored Lys48-linked polyubiquitin chains from mammalian cell extracts. Our
      study indicates that strategies for the rational design and engineering of
      polyubiquitin chain-selective binding in nonbiological polymers are possible,
      paving the way for the generation of reagents to probe unanchored polyubiquitin
      chains of different linkages and more broadly the 'ubiquitome'. All MS data have
      been deposited in the ProteomeXchange with identifier PXD004059
      (http://proteomecentral.proteomexchange.org/dataset/PXD004059).

PMID- 27037517
TI  - Interaction between living bone particles and rhBMP-2 in large segmental defect
      healing in the rat femur.
AB  - Orthopedic surgeons sometimes combine recombinant, human BMP-2 with autograft
      bone when dealing with problematic osseous fractures. Although some case reports
      indicate success with this off-label strategy, there have been no randomized
      controlled trials. Moreover, a literature search revealed only one pre-clinical
      study and this was in a cranial defect model. The present project examined the
      consequences of combining BMP-2 with particles of living bone in a rat femoral
      defect model. Human bone particles were recovered with a reamer-irrigator
      aspirator (RIA). To allow acceptance of the xenograft as surrogate autograft,
      rats were administered an immunosuppressive cocktail that does not interfere with
      bone healing. Implantation of 200 ug living bone particles generated a small
      amount of new bone and defects did not heal. Graded amounts of BMP-2 that alone
      provoked no healing (1.1 ug), borderline healing (5.5 ug), or full healing (11
      ug) were added to this amount of bone particles. Addition of BMP-2 (1.1 ug)
      increased osteogenesis, and produced bridging in 2 of 7 defects. The combination
      of BMP-2 (5.5 ug) and bone particles made healing more reliable and advanced the
      maturation of the regenerate. Bone formation with BMP-2 (11 ug) and bone
      particles showed improved maturation. Thus, the combination of autograft and BMP
      2 may be helpful clinically under conditions where the healing response is
      suboptimal. (c) 2016 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 34:2137-2145, 2016. Clinical significance These
      data support the clinical use of recombinant, human BMP-2 with autograft bone
      when treating large segmental osseous defects. The combination leads to greater
      bone formation and accelerates the maturation of the regenerate.

PMID- 27037518
TI  - Computer simulations of reentrant activity in the rabbit sinoatrial node.
AB  - With the aid of detailed computer simulations, we have estimated distributions of
      membrane potential and ionic currents in the core region of a sinoatrial node
      reentry. We observe reduced amplitudes of the measured quantities in the core;
      the core sizes for potential and currents did not always coincide. Simulations
      revealed that acetylcholine, when applied in the vicinity of unstable reentry,
      attracted the reentry to become the core and to stabilize its rotation.
      Anatomically detailed simulations of sinoatrial node and surrounding atrial
      tissue revealed that reentry always rotated around small strips of connective
      tissue. Acetylcholine superfusion over superior part of the sinoatrial node
      resulted in a drift of reentry in the cranial direction. Under the latter
      conditions, reentry may coexist with the pacemaker in the caudal part of the
      sinoatrial node. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037519
TI  - CHILD SEXUAL ABUSE, BULLYING, CYBERBULLYING, AND MENTAL HEALTH PROBLEMS AMONG
      HIGH SCHOOLS STUDENTS: A MODERATED MEDIATED MODEL.
AB  - BACKGROUND: Child sexual abuse is associated with adverse outcomes, including
      heightened vulnerability that may translate into risk of revictimization. The
      aims of the study were: (1) to explore the direct and indirect links between
      child sexual abuse and cyberbullying, bullying, and mental health problems and
      (2) to study maternal support as a potential protective factor. METHODS:
      Teenagers involved in the two first waves of the Quebec Youths' Romantic
      Relationships Survey (N = 8,194 and 6,780 at Wave I and II, respectively)
      completed measures assessing child sexual abuse and maternal support at Wave I.
      Cyberbullying, bullying, and mental health problems (self-esteem, psychological
      distress, and suicidal ideations) were evaluated 6 months later. RESULTS: Rates
      of cyberbullying in the past 6 months were twice as high in sexually abused teens
      compared to nonvictims both for girls (33.47 vs. 17.75%) and boys (29.62 vs.
      13.29%). A moderated mediated model revealed a partial mediation effect of
      cyberbullying and bullying in the link between child sexual abuse and mental
      health. Maternal support acted as a protective factor as the conditional indirect
      effects of child sexual abuse on mental health via cyberbullying and bullying
      were reduced in cases of high maternal support. CONCLUSIONS: Results have
      significant relevance for prevention and intervention in highlighting the
      heightened vulnerability of victims of child sexual abuse to experience both
      bullying and cyberbullying. Maternal support may buffer the risk of developing
      mental health distress, suggesting that intervention programs for victimized
      youth may profit by fostering parent involvement.

PMID- 27037520
TI  - An Enzyme-Based Half-Adder and Half-Subtractor with a Modular Design.
AB  - A half-adder and a half-subtractor have been realized using enzymatic reaction
      cascades performed in a flow cell device. The individual cells were modified with
      different enzymes and assembled in complex networks to perform logic operations
      and arithmetic functions. The modular design of the logic devices allowed for
      easy re-configuration, enabling them to perform various functions. The final
      output signals, represented by redox species [Fe(CN)6 ](3-/4-) or NADH/NAD(+) ,
      were analyzed optically to derive the calculation results. These output signals
      might be applicable in the future for actuation processes, for example, substance
      release activated by logically processed signals. 

PMID- 27037521
TI  - Stenamoeba polymorpha, a New Species Isolated from Domesticated Horse Equus ferus
      caballus.
AB  - A new species of lobosean amoeba, Stenamoeba polymorpha n. sp., was isolated from
      the diarrheic stool of a domesticated horse in Great Falls Virginia, U.S. It
      shares characteristics with the five other described Stenamoeba species. However,
      electron microscopy revealed S. polymorpha has a substantially thickened cell
      surface lamina. Under light microscopy, the amoebae had a dynamic polymorphic
      appearance because hyaloplasm readily formed and resorbed subpseudopodia from any
      peripheral region of the cell. While in locomotion, the amoebae produced
      subpseudopodia that led and alternated the direction of movement with an apparent
      zigzag path. Sometimes, stationary amoebae had a vertical cell posture that was
      substantially taller than wide or long. The new species description is also
      supported by small subunit ribosomal ribonucleic acid gene analyses using
      phylogenies with both broad and narrow taxon sampling, pairwise nucleotide
      comparisons, and in-silico secondary structure predictions. The latter suggested
      Stenamoeba spp. discriminatory motifs in variable region eight. Stenamoeba
      polymorpha n. sp. is the first of its genus to be recovered from mammal feces,
      the first to yield a potential group one intron and the second described from
      North America. Here, the phylogenies suggest Stenamoeba limacina is this new
      species' nearest known relative.

PMID- 27037522
TI  - The Length and Flexibility of the 2-Substituent of 9-Ethyladenine Derivatives
      Modulate Affinity and Selectivity for the Human A2A Adenosine Receptor.
AB  - The A2A adenosine receptor (A2A AR) is a key target for the development of
      pharmacological tools for the treatment of central nervous system disorders.
      Previous works have demonstrated that the insertion of substituents at various
      positions on adenine leads to A2A AR antagonists with affinity in the micromolar
      to nanomolar range. In this work, a series of 9-ethyladenine derivatives bearing
      phenylalkylamino, phenylakyloxy or phenylakylthio groups of different lengths at
      the 2-position were synthesised and tested against the human adenosine receptors.
      The derivatives showed sub-micromolar affinity for these membrane proteins. The
      further introduction of a bromine atom at the 8-position has the effect of
      improving the affinity and selectivity for all ARs and led to compounds that are
      able bind to the A2A AR subtype at low nanomolar levels. Functional studies
      confirmed that the new adenine derivatives behave as A2A AR antagonists with half
      maximal inhibitory concentration values in the nanomolar range. Molecular
      modelling studies provide a description of the possible binding mode of these
      compounds at the A2A AR and an interpretation of the affinity data at this AR
      subtype.

PMID- 27037523
TI  - Delayed pressure urticaria treated with the selective serotonin reuptake
      inhibitor escitalopram.
AB  - There is increasing evidence of platelet activation and systemic inflammation in
      chronic spontaneous urticaria and delayed pressure urticaria (DPU). Inflammation
      may be central to understanding the high comorbidity of depression and anxiety in
      patients with chronic urticaria (CU). We report a case of DPU and depression in a
      patient, which responded favourably to treatment with the selective serotonin
      reuptake inhibitor (SSRI) escitalopram. Sustained administration of SSRIs is
      associated with downregulation of serotonin transporters/receptors and depletion
      of platelet stored serotonin, which may reduce the ability of platelets to
      aggregate after thrombotic triggers. SSRIs are easier to manage and have
      significantly less disturbing adverse effects and cardiotoxicity than the
      tricyclic antidepressants (TCAs). SSRIs may represent an alternative to the
      traditional use of TCAs in treatment of CU. 

PMID- 27037524
TI  - Reply.

PMID- 27037525
TI  - Distress tolerance among substance users is associated with functional
      connectivity between prefrontal regions during a distress tolerance task.
AB  - Distress tolerance (DT), defined as the ability to persist in goal directed
      behavior while experiencing affective distress, is implicated in the development
      and maintenance of substance use disorders. While theory and evidence indicate
      that cortico-limbic neural dysfunction may account for deficits in goal directed
      behavior while experiencing distress, the neurobiological mechanisms of DT have
      yet to be examined. We modified a computerized DT task for use in functional
      magnetic resonance imaging (fMRI), the Paced Auditory Serial Addition Task (PASAT
      M), and examined the neural correlates and functional connectivity of DT among a
      cohort of substance users (n = 21; regular cocaine and nicotine users) and
      healthy controls (n = 25). In response to distress during the PASAT-M, we found
      greater activation in a priori cortico-limbic network ROIs, namely the right
      insula, anterior cingulate cortex (ACC), bilateral medial frontal gyrus (MFG),
      right inferior frontal gyrus (IFG) and right ventromedial prefrontal cortex
      (vmPFC) significantly predicted higher DT among substance users, but not healthy
      controls. In addition, greater task-specific functional connectivity during
      distress between the right MFG and bilateral vmPFC/sgACC was associated with
      higher DT among substance users, but not healthy controls. The observed positive
      relationship between DT and neural activation in cortico-limbic structures, as
      well as functional connectivity between the rMFG and vmPFC/sgACC, is in line with
      theory and research suggesting the importance of these structures for persisting
      in goal directed behavior while experiencing affective distress.

PMID- 27037526
TI  - h-Prune is associated with poor prognosis and epithelial-mesenchymal transition
      in patients with colorectal liver metastases.
AB  - The prognosis of patients with colorectal liver metastases (CRLM) remains low
      despite advances in chemotherapy and surgery. The expression of h-prune (human
      homolog of Drosophila prune protein; HGNC13420), an exopolyphosphatase, is
      correlated with progression and aggressiveness in several cancers and promotes
      migration and invasion. We investigated the role of h-prune in CRLM. To
      investigate the role of h-prune, immunohistochemical analysis for h-prune was
      performed in 87 surgically resected specimens of CRLM obtained between 2001 and
      2009 at the Hiroshima University Hospital. Immunohistochemical analysis revealed
      positive staining for h-prune in 24 (28%) cases. The overall survival rate was
      significantly lower in h-prune-positive cases than in h-prune-negative cases (p =
      0.003). Multivariate analysis showed that h-prune positivity was the only
      independent factor related to poor overall survival of patients after curative
      hepatectomy of CRLM. In vitro and in vivo, h-prune-knocked-down and h-prune
      overexpressing cells were analyzed. In vitro, h-prune was associated with
      increased cell motility and upregulation of epithelial-mesenchymal transition
      (EMT) markers. In a mouse model, h-prune was associated with invasion of the
      tumor and distant metastases. In summary, h-prune expression is a useful marker
      to identify high-risk patients for resectable colorectal liver metastasis. h
      Prune expression is necessary for cancer cell motility and EMT and is associated
      with liver and lung metastasis in colorectal cancer cells. h-Prune could be a new
      prognostic marker and molecular target for CRLM.

PMID- 27037527
TI  - Clinical repigmentation patterns in paediatric vitiligo.
AB  - BACKGROUND: Repigmentation is an essential outcome measure in vitiligo. However,
      clinical studies describing vitiligo repigmentation patterns are lacking.
      OBJECTIVES: To assess and clearly define the repigmentation patterns in a series
      of patients with vitiligo, correlating these with clinicoepidemiological
      characteristics. METHODS: Patients with vitiligo seen at least at twice (initial
      consultation and follow-up visit) in the Department of Paediatric Dermatology,
      Hopital Pellegrin des Enfants, Bordeaux University Hospital from 2006 to 2014
      were included. Clinical photographs and case records were reviewed. RESULTS:
      There were 109 patients (64 female, 45 male) mostly with Fitzpatrick skin type
      III (n = 67, 61%). The majority had nonsegmental (n = 71, 65%) or segmental
      vitiligo (n = 29, 27%). In total 172 representative vitiligo lesions were
      analysed. Overall, a combined pattern of repigmentation was most commonly seen (n
      = 106, 62%). The combined pattern occurred more frequently in patients with
      segmental vs. nonsegmental vitiligo (P = 0.009), whereas the diffuse pattern was
      more frequent in the latter (P = 0.007). Diffuse repigmentation was the
      predominant pattern on the eyelids (P < 0.001). We observed a new pattern in
      sites with few to absent hair follicles, which we propose to call 'medium spotted
      repigmentation'. This begins as circular macules of repigmentation, wider than 5
      mm in diameter, which, from the outset, are larger than the initial macules of
      perifollicular repigmentation. This study is limited by its retrospective nature
      and small sample size for subgroup assessment. CONCLUSIONS: The combined pattern
      of repigmentation was most frequently observed. Medium spotted repigmentation is
      a new pattern, which will benefit from larger studies for a better understanding.

PMID- 27037528
TI  - Triply Linked Corrole Dimers.
AB  - The oxidation of 10-10' singly linked corrole dimers with DDQ at low
      concentration in CHCl3 afforded meso-meso, beta-beta, beta-beta triply linked 2H
      corrole dimers (with two inner NH groups in each corrole unit), which exhibited
      characteristic (1) H NMR and absorption spectra attributable to their nonaromatic
      electronic networks. These 2H-corrole dimers were reduced with NaBH4 to aromatic
      3H-corrole dimers, which were unstable and easily oxidized back to the 2H-corrole
      dimers upon exposure to air. Bis(zinc(II)) complexes of the 2H-corrole dimers
      were synthesized and characterized as rare examples of nonaromatic zinc(II)
      corrole complexes.

PMID- 27037529
TI  - The mystery of the thymus gland.
AB  - The thymus is the last organ in the human body to have its mechanisms fully
      understood, having had its function fully delineated more than 50 years ago
      (Miller , Tissue Antigens 63:509-517). Prior to this, the thymus gland has had an
      interesting history with theories having included a role in fetal growth and
      development before becoming more sinisterly, a cause of sudden infant death in
      the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr
      2:877-881). Until Miller (, Lancet 278:748-749) eventually proved its primarily
      immunological role, the history of this mysterious gland has closely mirrored the
      history of medicine itself, troubling the minds of pathologists such as Virchow
      (, Ueber die Chlorose und die damit zusammenhangenden Anomalien im
      Gefassapparate, insbesondere uber "Endocarditis puerperalis," vorgetragen in der
      Sitzung der Berliner Geburtshulflichen Gesellschaft vom 12) and Grawitz (, Deut
      Med Wochenschr 22:429-431), surgeons such as Astley Cooper (, The Anatomy of the
      Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical
      epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305-326]. This
      article will hopefully be of interest therefore to both clinician and historian
      alike. Clin. Anat. 29:679-684, 2016. (c) 2016 Wiley Periodicals, Inc. 

PMID- 27037530
TI  - Incontinentia pigmenti in a father and daughter.

PMID- 27037531
TI  - Support Jordan.

PMID- 27037532
TI  - Novel Piperine Derivatives with Antidiabetic Effect as PPAR-gamma Agonists.
AB  - Piperine is an alkaloid responsible for the pungency of black pepper. In this
      study, piperine isolated from Piper nigrum L. was hydrolyzed under basic
      condition to obtain piperic acid and was used as precursor to carry out the
      synthesis of twenty piperine derivatives containing benzothiazole moiety. All the
      benzothiazole derivatives were evaluated for their antidiabetic potential by OGT
      test followed by assessment of active derivatives on STZ-induced diabetic model.
      It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed
      significantly higher antidiabetic activity in comparison with rosiglitazone
      (standard). Furthermore, these active derivatives were evaluated for their action
      as PPAR-gamma agonists demonstrating their mechanism of action. The effects on
      body weight, lipid peroxidation, and hepatotoxicity after administration with
      active derivatives were also studied to further establish these derivatives as
      lead molecules for treatment of diabetes with lesser side-effects. 

PMID- 27037533
TI  - Chromogranin A and neurone-specific enolase serum levels as predictors of
      treatment outcome in patients with metastatic castration-resistant prostate
      cancer undergoing abiraterone therapy.
AB  - OBJECTIVE: To determine the impact of elevated neuroendocrine serum markers on
      treatment outcome in patients with metastatic castration-resistant prostate
      cancer (mCRPC) undergoing treatment with abiraterone in a post-chemotherapy
      setting. PATIENTS AND METHOD: Chromogranin A (CGa) and neurone-specific enolase
      (NSE) were determined in serum drawn before treatment with abiraterone from 45
      patients with mCRPC. Outcome measures were overall survival (OS), prostate
      specific antigen (PSA) response defined by a PSA level decline of >=50%, PSA
      progression-free survival (PSA-PFS), and clinical or radiographic PFS. RESULTS:
      The CGa and NSE serum levels did not correlate (P = 0.6). Patients were
      stratified in to low- (nine patients), intermediate- (18) or high-risk (18)
      groups according to elevation of none, one, or both neuroendocrine markers,
      respectively. The risk groups correlated with decreasing median OS (median OS not
      reached vs 15.3 vs 6.6 months; P < 0.001), decreasing median clinical or
      radiographic PFS (8.3 vs 4.4 vs 2.7 months; P = 0.001) and decreasing median PSA
      PFS (12.0 vs 3.2 vs 2.7 months; P = 0.012). In multivariate Cox regression
      analysis the combination of CGa and NSE (>=1 marker positive vs both markers
      negative) remained significant predictors of OS, clinical or radiographic PFS,
      and PSA-PFS. We did not observe a correlation with PSA response (63% vs 35% vs
      31%; P = 0.2). CONCLUSION: Chromogranin A and NSE did not predict PSA response in
      patients with mCRPC treated with abiraterone. However, we observed a correlation
      with shorter PSA-PFS, clinical or radiographic PFS, and OS. This might be due to
      an elevated risk of developing resistance under abiraterone treatment related to
      neuroendocrine differentiation.

PMID- 27037534
TI  - From Opportunity to Action.

PMID- 27037535
TI  - Filling the Gap for Early-Stage Breast Cancer Follow-Up: An Overview for Primary
      Care Providers.
AB  - Earlier detection and newer treatments now make breast cancer highly survivable,
      and breast cancer survivors are the largest female cancer survivor group in the
      United States. With earlier detection, more women are being diagnosed with early
      stage breast cancer and need follow-up care. With the increasing number of breast
      cancer survivors, there is a projected shortage in the workforce of oncology
      specialists to care for these women. The American Society of Clinical Oncology
      recommends that breast cancer follow-up care can be provided by an oncologist or
      primary care provider, as long as the primary care provider has spoken to the
      oncologist about appropriate follow-up care. Several studies have shown that
      primary care providers and oncologists have comparable outcomes for follow-up
      care of women with early-stage breast cancer. The National Comprehensive Cancer
      Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) are considered
      the gold standard for breast cancer treatment and follow-up. These guidelines are
      clear and straightforward. Using knowledge of the NCCN Guidelines, primary care
      providers can fill the gap for follow-up care of women with early-stage breast
      cancer. 

PMID- 27037536
TI  - Index of ACNM Documents and Publications, March 2016.

PMID- 27037537
TI  - Choosing Where to Give Birth.

PMID- 27037538
TI  - A screening of multiple classes of pharmaceutical compounds for effect on
      preadult salmon lice Lepeophtheirus salmonis.
AB  - The salmon louse, Lepeophtheirus salmonis Kroyer, is the major obstacle facing a
      sustainable future for farmers of salmonids in the North Atlantic Ocean.
      Medicinal compounds have been the most utilized tool to prevent salmon lice
      infestation; however, the active compounds have become less effective or
      considered environmentally unfriendly in the past years. Novel medicinal
      compounds are thus highly desired. In two experiment series, 26 medicinal
      compounds were screened for their efficacy against salmon lice, in a 30-min
      exposure and 24-h exposure, respectively. Pyriprole, imidacloprid, cartap and
      spinetoram were effective at 50 mg L(-1) in the short-time exposure. In the 24-h
      exposure, pyriprole, propoxur, cartap, imidacloprid, fenoxycarb, pyriproxyfen,
      nitenpyram, spinetoram, spiromesifen and diflubenzuron induced a high level of
      immobilization at 5 mg L(-1) . The EC50 values of the effective compounds were
      calculated in further titration studies for both exposure periods. Several
      physiological and biochemical pathways were discovered as possible targets for
      medicinal intervention against the salmon louse. 

PMID- 27037539
TI  - Influence of body habitus on feasibility and outcome of laparoscopic liver
      resections: a prospective study.
AB  - BACKGROUND: The aim of the present study was to prospectively investigate whether
      the anthropometric measures of A Body Shape Index (ABSI, taking into account
      waist circumference adjusted for height and weight) affects feasibility and
      outcome of laparoscopic liver resections. METHODS: One hundred patients
      undergoing laparoscopic liver resection were prospectively included in the study
      (2014-2015). Preoperative clinical parameters, including body mass index (BMI)
      and ABSI were evaluated for associations with intraoperative outcome and
      postoperative results (morbidity, mortality and functional recovery). RESULTS:
      Twenty-two and 78 patients underwent major and minor hepatectomies, respectively.
      Conversion rate was 9%, mean blood loss was 210 +/- 115 ml. Postoperative
      morbidity was 15% and mortality was nil. Mean length of stay was 4 days. When
      considering the entire series, ABSI was not associated with intra and
      postoperative outcome. After stratification of patients according to difficulty
      score, Pearson's correlation demonstrated an association between ABSI and
      intraoperative blood loss (P = 0.03) and time for functional recovery (P = 0.05)
      in patients undergoing resections with high score of difficulty. CONCLUSION: Body
      habitus has an influence on outcome of laparoscopic liver resections with high
      degree of difficulty, while feasibility and outcome of low difficulty resections
      seem not to be affected by anthropometric measures.

PMID- 27037540
TI  - Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink
      in the 2013-2014 and 2014-2015 seasons.
AB  - PURPOSE: The changes in each year in influenza vaccine antigenic components as
      well as vaccine administration patterns may pose new risks of adverse events
      following immunization (AEs). To evaluate the safety of influenza vaccines
      annually administered to people >= 6 months, we conducted weekly post licensure
      surveillance for seven pre-specified adverse events following receipt of
      influenza vaccines during the 2013-2014 and 2014-2015 seasons in the Vaccine
      Safety Datalink (VSD). METHODS: We used both a historically-controlled cohort
      design with the Poisson-based maximized sequential probability ratio test
      (maxSPRT) and a self-controlled risk interval (SCRI) design with the binomial
      based maxSPRT. For each adverse event outcome, we defined the risk interval on
      the basis of biologic plausibility and prior literature. For the historical
      cohort design, numbers of expected adverse events were calculated from the prior
      seven seasons, adjusted for age and site. For the SCRI design, a comparison
      window was defined either before vaccination or after vaccination, depending on
      each specific outcome. RESULTS: An elevated risk of febrile seizures 0-1 days
      following trivalent inactivated influenza vaccine (IIV3) was identified in
      children aged 6-23 months during the 2014-2015 season using the SCRI design. We
      found the relative risk (RR) of febrile seizures following concomitant
      administration of IIV3 and PCV13 was 5.3 with a 95% CI 1.87-14.75. Without
      concomitant PCV 13 administration, the estimated risk decreased and was no longer
      statistically significant (RR: 1.4; CI: 0.54 - 3.61). CONCLUSION: No increased
      risks, other than for febrile seizures, were identified in influenza vaccine
      safety surveillance during 2013-2014 and 2014-2015 seasons in the VSD. Copyright
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037541
TI  - Assessing the risks of pesticides to threatened and endangered species using
      population modeling: A critical review and recommendations for future work.
AB  - United States legislation requires the US Environmental Protection Agency to
      ensure that pesticide use does not cause unreasonable adverse effects on the
      environment, including species listed under the Endangered Species Act (ESA;
      hereafter referred to as listed species). Despite a long history of population
      models used in conservation biology and resource management and a 2013 report
      from the US National Research Council recommending their use, application of
      population models for pesticide risk assessments under the ESA has been minimal.
      The pertinent literature published from 2004 to 2014 was reviewed to explore the
      availability of population models and their frequency of use in listed species
      risk assessments. The models were categorized in terms of structure, taxonomic
      coverage, purpose, inputs and outputs, and whether the models included density
      dependence, stochasticity, or risk estimates, or were spatially explicit. Despite
      the widespread availability of models and an extensive literature documenting
      their use in other management contexts, only 2 of the approximately 400 studies
      reviewed used population models to assess the risks of pesticides to listed
      species. This result suggests that there is an untapped potential to adapt
      existing models for pesticide risk assessments under the ESA, but also that there
      are some challenges to do so for listed species. Key conclusions from the
      analysis are summarized, and priorities are recommended for future work to
      increase the usefulness of population models as tools for pesticide risk
      assessments. Environ Toxicol Chem 2016;35:1904-1913. (c) 2016 SETAC.

PMID- 27037542
TI  - Financial Neutrality for Living Organ Donors: Reasoning, Rationale, Definitions,
      and Implementation Strategies.
AB  - In the United States, live organ donation can be a costly and burdensome
      undertaking for donors. While most donation-related medical expenses are covered,
      many donors still face lost wages, travel expenses, incidentals, and potential
      for future insurability problems. Despite widespread consensus that live donors
      (LD) should not be responsible for the costs associated with donation, little has
      changed to alleviate financial burdens for LDs in the last decade. To achieve
      this goal, the transplant community must actively pursue strategies and policies
      to eliminate unreimbursed out-of-pocket costs to LDs. Costs should be more
      appropriately distributed across all stakeholders; this will also make live
      donation possible for people who, in the current system, cannot afford to
      proceed. We propose the goal of LD "financial neutrality," offer an operational
      definition to include the coverage/reimbursement of all medical, travel, and
      lodging costs, along with lost wages, related to the act of donating an organ,
      and guidance for consideration of medical care coverage, and wage and other
      expense reimbursement. The intent of this report is to provide a foundation to
      inform discussion within the transplant community and to advance initiatives for
      policy and resource allocation.

PMID- 27037543
TI  - Practical and reproducible estimation of myenteric interstitial cells of Cajal in
      the bowel for diagnostic purposes.
AB  - BACKGROUND: Histological assessment of the interstitial cells of Cajal (ICCs) in
      the bowel is important for diagnosing patients with gastrointestinal
      neuromuscular diseases (GINMD). Although the International Working Group on GINMD
      proposed reporting a decrease in ICC number of more than 50%, quantitative
      methods used in literature are not practical for daily routine of the
      pathologist. Consequently, this study presents a straightforward semiquantitative
      estimation method for myenteric ICCs of the bowel. METHODS: Formalin-fixed
      paraffin-embedded sections from small bowel (n = 87) and colon (n = 159) were
      collected to create two control groups and four groups composed of patients with
      gastrointestinal motility disorders. The control groups included material of
      resection and autopsy origin, respectively. Samples were stained with CD117 (c
      kit) antibody to estimate the myenteric ICC network. Scores of two observers were
      compared to analyze inter- and intraobserver agreement and reliability. KEY
      RESULTS: Interobserver reliability was almost perfect for small bowel (intraclass
      correlation coefficient 0.847; 95% confidence interval [CI]: 0.774-0.897) and
      substantial for colon (0.683; 95% CI: 0.591-0.758). Almost perfect intraobserver
      reliability was found (intraclass correlation coefficient 0.918; 95% CI: 0.874
      0.947). The small bowel showed more myenteric ICCs than the colon. Neither
      significant differences between colonic regions were found nor were there any
      differences in the orientation of the sections. CONCLUSIONS & INFERENCES: The
      proposed estimation method for the myenteric ICC network showed generally good
      agreement and reliability. As the method is semiquantitative, simple, and capable
      to differentiate between normal and diseased tissue, it can be used in routine
      diagnostics of gastrointestinal neuromuscular disorders.

PMID- 27037544
TI  - Comparison of transradial coronary procedures via right radial versus left radial
      artery approach: A meta-analysis.
AB  - INTRODUCTION: Coronary angiography and angioplasty via transradial approach is
      shown to be associated with significant reduction in access site complications.
      Due to a lack of sufficient data, the use of the right or left radial approach is
      still operator-dependent. We performed a meta-analysis of prospective randomized
      studies to compare right versus left radial artery approach for coronary
      procedures. METHODS: We found 12 randomized studies meeting the predetermined
      inclusion criteria. A total of 6,450 patients were included in the meta-analysis
      of which 3,217 patients underwent coronary procedures via right radial approach
      and 3,233 patients via left radial approach. The primary endpoint was the
      comparison of fluoroscopy time, procedure time, contrast use and cross-over rates
      between two radial approaches. RESULTS: Pooled analysis of the included studies
      showed a similar rate of cross-over events (4.2% for right radial approach vs.
      4.1% for left radial approach, odds ratio (OR)=1.08, P = 0.68), and similar total
      procedure times (18.8 +/- 10.3 min vs. 18.1 +/- 10.0 min, standard difference
      (SD) of the mean = 0.09, P = 0.162) between the two radial approaches. However,
      the right radial approach was found to be associated with minimally longer
      fluoroscopy times (5.8 +/- 4.4 min vs. 5.3 +/- 4.2 min, SD of the mean = 0.157, P
      < 0.001) and greater contrast use (84 +/- 35 mL vs. 82 +/- 34 mL, SD of the mean
      = 0.082, P = 0.003). Access site complications and the incidence of stroke were
      similar between two radial approaches. CONCLUSION: Our meta-analysis suggests a
      small but statistically significant difference in terms of contrast use and
      fluoroscopy time in favor of coronary procedures performed via left radial
      approach in comparison to right radial approach without any significant
      difference in access site or other procedural complications between the two
      radial approaches. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037545
TI  - A potential role for cytomegalovirus in a facial ulcer in a renal transplant
      recipient.
AB  - Cytomegalovirus infection (CMV) is a well-known consequence of immunosuppression
      and one of the expected pathogens in recipients of solid organs such as renal
      transplant recipients (RTRs). Infection by CMV in immunocompromised settings can
      be life-threatening since many organs are involved and affected. Skin involvement
      has been rarely reported. In this report, we present a highly immunosuppressed
      RTR with CMV infection manifested as ulcerative skin lesions on the face, along
      with allograft dysfunction diagnosed by biopsy of the skin and the renal
      allograft, in addition to the presence of viral DNA in the tissue and
      antigenemia, which resolved following antiviral treatment. To the best of our
      knowledge, this is the first report in the literature of facial skin involvement
      induced by CMV in an RTR. This report emphasizes the value of early biopsy in
      RTRs with skin lesions and highlights CMV infection as a possible etiology.

PMID- 27037546
TI  - The Effect of Motivational Interviewing-Based Counseling During Outpatient
      Provider Initiated HIV Testing on High-Risk Sexual Behavior in Rural Uganda.
AB  - Provider-initiated HIV testing and counseling (PITC) has rapidly expanded in many
      countries including Uganda. However, because it provides HIV prevention
      information without individualized risk assessment and risk reduction counseling
      it may create missed opportunities for effective HIV prevention counseling. Our
      objective was to assess the effect of a brief motivational interviewing-based
      intervention during outpatient PITC in rural Uganda compared to Uganda's standard
      of-care PITC at reducing HIV transmission-relevant sexual risk behavior. We
      enrolled 333 (160 control, 173 intervention) participants in a historical control
      trial to test the intervention vs. standard-of-care. Participants received PITC
      and standard-of-care or the intervention counseling and we assessed sexual risk
      behavior at baseline and 3 and 6 months follow-up. The intervention condition
      showed 1.5-2.4 times greater decreases in high risk sexual behavior over time
      compared to standard-of-care (p = 0.015 and p = 0.004). These data suggest that
      motivational interviewing based counseling during PITC may be a promising
      intervention to reduce high-risk sexual behavior and potentially reduce risk of
      HIV infection.

PMID- 27037547
TI  - A Multi-Group Latent Class Analysis of Chronic Medical Conditions Among Men Who
      Have Sex with Men.
AB  - Until recently, research on the health of gay and other men who have sex with men
      (MSM) has focused on risk for and the health consequences of HIV and other
      sexually transmitted infections. A multigroup latent class analysis examined a
      range of lifetime chronic medical conditions (CMCs) among MSM. Covariates
      included sociodemographics, substance use, psychological distress, and HIV
      serostatus. A two-class model best fit the medical condition data: a low
      probabilities class for most CMCs and a moderate to high probabilities (MHP)
      class. HIV serostatus was associated with increased within-class probabilities
      for some CMCs, particularly gastrointestinal and skin disorders. Only increasing
      age and use of erectile dysfunction drugs were directly associated with increased
      odds of being in the MHP class whereas methamphetamine use, identifying as gay,
      and lower alcohol use were indirectly associated. Implications of the findings
      for future research and the health care needs of MSM are discussed.

PMID- 27037548
TI  - Overview of the University of Pittsburgh/amfAR Training Program in HIV Prevention
      Research for MSM and Male-to-Female Transgender Populations in Low- and Middle
      Income Countries.
AB  - Gay men, other men who have sex with men and transgender (GMT) populations suffer
      a disproportionate burden of HIV disease around the globe, which is directly
      attributable to the virulently homophobic environments in which many GMT people
      live. In addition to the direct effects of homophobia on GMT individuals, the
      ongoing marginalization of GMT people has meant that there is limited social
      capital on which effective HIV prevention and care programs can be built in many
      low- and middle-income countries (LMIC). Thus, meaningful responses meant to
      address the dire situation of GMT populations in LMIC settings must include a
      combination of bold and innovative approaches if efforts to end the epidemic are
      to have any chance of making a real difference. The HIV Scholars Program at the
      University of Pittsburgh's Center for LGBT Health Research is a prime example of
      a creative and dynamic approach to raising the expertise needed within GMT
      populations to respond to the global HIV/AIDS pandemic.

PMID- 27037549
TI  - Impact of Timing of ECMO Initiation on Outcomes After Pediatric Heart Surgery: A
      Multi-Institutional Analysis.
AB  - Little is known about the relationship of timing of extracorporeal membrane
      oxygenation (ECMO) initiation on patient outcomes after pediatric heart surgery.
      We hypothesized that increasing timing of ECMO initiation after heart surgery
      will be associated with worsening study outcomes. Patients aged <=18 years
      receiving ECMO after pediatric cardiac surgery at a Pediatric Health Information
      System-participating hospital (2004-2013) were included. Outcomes evaluated
      included in-hospital mortality, composite poor outcome, prolonged length of ECMO,
      prolonged length of mechanical ventilation, prolonged length of ICU stay, and
      prolonged length of hospital stay. Multivariable logistic regression models were
      fitted to study the probability of study outcomes as a function of timing from
      cardiac surgery to ECMO initiation. A total of 2908 patients from 42 hospitals
      qualified for inclusion. The median timing of ECMO initiation after cardiac
      surgery was 0 days (IQR 0-1 day; range 0-294 days). After adjusting for patient
      and center characteristics, increasing duration of time from surgery to ECMO
      initiation was not associated with higher mortality or worsening composite poor
      outcome. However, increasing duration of time from surgery to ECMO initiation was
      associated with prolonged length of ECMO, prolonged length of ventilation,
      prolonged length of ICU stay, and prolonged length of hospital stay. Although
      this relationship was statistically significant, the odds for prolonged length of
      ECMO, prolonged length of ventilation, prolonged length of ICU stay, and
      prolonged length of hospital stay increased by only 1-3 % for every 1-day
      increase in ECMO that may be clinically insignificant. We did not demonstrate any
      relationship between timing of ECMO initiation and mortality among the patients
      of varying age groups, and patients undergoing cardiac surgery of varying
      complexity. We concluded that increasing duration of time from surgery to ECMO
      initiation is not associated with worsening mortality. Our results suggest that
      ECMO is initiated at the appropriate time when dictated by clinical situation
      among patients of all age groups, and among patients undergoing heart operations
      of varying complexity. 

PMID- 27037550
TI  - Perinatal Decision Making for Preterm Infants with Congenital Heart Disease:
      Determinable Risk Factors for Mortality.
AB  - For premature infants with congenital heart disease (CHD), it may be unclear when
      the burdens of treatment outweigh potential benefits. Parents may thus have to
      choose between comfort care at birth and medical stabilization until surgical
      repair is feasible. Better defined outcome data, including risk factors for
      mortality, are needed to counsel expectant parents who are considering intensive
      care for premature infants with CHD. We sought to evaluate outcomes in this
      population to inform expectant parents considering intensive versus palliative
      care at birth. We performed a retrospective cohort study of infants born <34
      weeks who received intensive care with critical or moderately severe CHD
      predicted to require surgery in the neonatal period or the first 6 months of
      life. 46 % of 54 infants survived. Among non-survivors, 74 % died prior to
      surgery (median age 24 days). Of the infants that underwent surgery, 75 %
      survived. Survival was lower among infants <32 weeks gestational age (GA) (p =
      0.013), with birth weight (BW) <1500 g (p = 0.011), or with extra-cardiac
      anomalies (ECA) (p = 0.015). GA and ECA remained significant risk factors for
      mortality in multiple logistic regression analysis. In summary, GA < 32 weeks, BW
      < 1500 g, and ECA are determinable prenatally and were significant risk factors
      for mortality. The majority of infants who survived to cardiac intervention
      survived neonatal hospitalization, whereas most of the infants who died did so
      prior to surgery. For some expectant parents, this early declaration of mortality
      may support a trial of intensive care while avoiding burdensome interventions. 

PMID- 27037551
TI  - The Impact of a Designated Cardiology Team Involving Telemedicine Home Monitoring
      on the Care of Children with Single-Ventricle Physiology After Norwood
      Palliation.
AB  - We evaluated the effect of an interdisciplinary single-ventricle task force
      (SVTF) that utilizes a family-driven, telemedicine home monitoring program on
      clinical outcomes of stage II admissions and its acceptance by parents and
      cardiologists. Study population was divided into two cohorts, one with Norwood
      surgery dates before the SVTF (pre-SVTF) and one interventional (post-SVTF). Post
      SVTF data also included surveys of parents and cardiologists on the efficacy of
      the SVTF. Comparative and multivariate statistical testing was performed.
      Compared to the pre-SVTF group, the post-SVTF group had lower complications after
      stage II (18.4 vs. 34.1 %, p = 0.02), higher weight-for-age z scores at stage II
      (-1.5 +/- 0.97 vs. -1.58 +/- 1.34, p = 0.02) and were less likely to have a stage
      II weight-for-age z score below -2 (26.5 vs. 31.7 %, p = 0.03). A multivariate
      regression analysis showed providing a written red-flag action plan to parents at
      discharge was independently associated with higher weight at stage II (beta =
      0.42, p = 0.04) and higher weight-for-age z score (beta = 0.48, p = 0.02).
      Parents' satisfaction with SVTF (alpha = 0.97) was 4.34 +/- 0.62; (95 % CI 4.01
      4.67) and cardiologists' acceptance (alpha = 0.93) was 4.1 +/- 0.7 (95 % CI 3.79
      4.42). Development of SVTF was associated with a reduction in complications post
      stage II and improved weight status at stage II. A written red-flag action plan
      provided to parents at the time of Norwood discharge was associated with higher
      weight status at stage II. Parents and cardiologists expressed satisfaction with
      the utility of SVTF and encouraged expansion to cover all children with
      congenital heart disease. 

PMID- 27037552
TI  - Identification of ABCC2 as a binding protein of Cry1Ac on brush border membrane
      vesicles from Helicoverpa armigera by an improved pull-down assay.
AB  - Cry1Ac toxin-binding proteins from Helicoverpa armigera brush border membrane
      vesicles were identified by an improved pull-down method that involves coupling
      Cry1Ac to CNBr agarose combined with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). According to the LC-MS/MS results, Cry1Ac toxin could
      bind to six classes of aminopeptidase-N, alkaline phosphatase, cadherin-like
      protein, ATP-binding cassette transporter subfamily C protein (ABCC2), actin,
      ATPase, polycalin, and some other proteins not previously characterized as Cry
      toxin-binding molecules such as dipeptidyl peptidase or carboxyl/choline esterase
      and some serine proteases. This is the first report that suggests the direct
      binding of Cry1Ac toxin to ABCC2 in H. armigera.

PMID- 27037553
TI  - A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Determine the
      Effect of Romiplostim on Health-Related Quality of Life in Children with Primary
      Immune Thrombocytopenia and Associated Burden in Their Parents.
AB  - BACKGROUND: Chronic immune thrombocytopenia (ITP) in children can negatively
      impact their health-related quality of life (HRQoL) and impose a burden on their
      parents. This study sought to examine the effect of romiplostim on HRQoL and
      parental burden in children with primary ITP. PROCEDURE: This was a phase 3,
      randomized, double-blind, placebo-controlled study. Children aged <18 years with
      ITP >=6 months were randomly assigned to receive romiplostim or placebo for 24
      weeks. The Kids' ITP Tool (KIT) was used to measure HRQoL and was administered to
      patients and/or their parents at baseline and weeks 8, 16, and 25. Mean KIT
      scores at each assessment and mean changes in KIT scores from baseline were
      calculated overall by treatment group and platelet response status. Psychometric
      properties of the KIT were evaluated and the minimally important difference (MID)
      was estimated for different KIT versions. RESULTS: Sixty-two patients (42
      romiplostim and 20 placebo) were enrolled. Changes in KIT scores by treatment
      group showed numerically greater and more often statistically significant
      improvements from baseline to each assessment for children receiving romiplostim
      versus placebo. Mixed-effects analysis demonstrated statistically significantly
      greater reduction in parental burden from baseline in the romiplostim group
      versus placebo. Ranges for the MID were estimated as 9-13 points for the Child
      Self-Report version and 11-13 points for the Parent Impact version. CONCLUSIONS:
      The treatment with romiplostim may be associated with improved HRQoL in children
      with primary ITP and reduced burden to their parents.

PMID- 27037554
TI  - [Amblyopia. Epidemiology, causes and risk factors].
AB  - BACKGROUND: Amblyopia is the main cause for mostly monocular, impaired vision in
      childhood. Treatment and prevention of amblyopia is only effective during
      childhood. Ophthalmological screening of children does not yet exist in Germany.
      EPIDEMIOLOGY: The prevalence of amblyopia in Germany is 5.6%, which is higher
      than in reports from studies in Australia; however, the prevalence of amblyopia
      is not comparable in these studies due to different definitions of amblyopia and
      the inclusion/exclusion criteria of the study cohorts. At present it is unknown
      at what age ophthalmological screening should be carried out to prevent amblyopia
      and the appropriate frequency of screening examinations. CAUSES: Amblyopia is a
      disorder of the visual cortex that is due to suppression and deprivation of one
      eye leading to unilateral visual impairment. Approximately 50% of cases of
      amblyopia are caused by anisometropia, 25% by strabismus and in every sixth
      person by a combination of both. Other causes, such as unilateral congenital
      cataracts are relatively rare. RISK FACTORS: A variety of factors, such as ocular
      pathologies, premature birth, familial disposition and general diseases are
      associated with an increased risk for amblyopia.

PMID- 27037555
TI  - Helical, Axial, and Central Chirality Combined in a Single Cage: Synthesis,
      Absolute Configuration, and Recognition Properties.
AB  - The synthesis of eight enantiopure molecular cages (four diastereomeric pairs of
      enantiomers) comprising a helically chiral cyclotriveratrylene (CTV) unit, three
      axially chiral binaphthol linkages, and three centrally asymmetric carbon atoms
      of a trialkanolamine core, is described. These new cages constitute a novel
      family of hemicryptophanes, which combine three classes of chirality. Their
      absolute configuration was successfully assigned by a chemical correlation method
      to overcome the signals overlap in the ECD spectra of the binaphtol and CTV
      units. Stereoselective recognition of glucose and mannose derivatives was
      investigated with these new chiral cages. Excellent enantio- and
      diastereoselectivity were reached, since in some cases, both exclusive enantio-
      and diastereo-discrimination have been observed. In addition, compared with the
      most relevant hemicryptophanes, these new cages also exhibit improved binding
      affinities. 

PMID- 27037556
TI  - Psychometric Properties of the DASS-21 Among Latina/o College Students by the US
      Mexico Border.
AB  - Anxious-depression symptomatology is frequently encountered among Latina/o
      individuals. There is a dearth of studies that examine this mixed class of
      anxiety and depression symptomatology, especially among Latina/o college students
      by the US-Mexico border. A total of 505 participants from rural institutions of
      higher education completed the DASS21. Psychometric properties were measured by
      means of confirmatory and exploratory factor analysis (EFA). A multivariate
      analysis of variance (MANOVA) was conducted to determine gender differences in
      depression, anxiety and stress. Among women, 18 % reported at least moderate
      levels of depressive symptoms, 33.1 % reported at least moderate levels of
      anxiety symptoms, and 16.4 % reported at least moderate levels of stress. In men,
      15.9 % reported at least moderate levels of depressive symptoms, 34.1 % reported
      at least moderate levels of anxiety symptoms, and 12.9 % reported at least
      moderate levels of stress. The EFA supported a one dimension factor
      (anxious/stress-depression) among this sample of Latina/o college students
      (Bartlett's test = 4960.9; df = 210; p <= 0.01; Kaiser-Meyer-Olkin = 0.95). The
      MANOVA found no significant gender differences in depression, anxiety
      symptomatology and stress [Wilks'Lambda = 0.99; F = (3, 500) = 2.41; p = 0.07].
      The DASS-21 showed a one dimensional construct of anxious/stress-depression
      symptomatology in a Latina/o rural undergraduate sample, raising awareness to the
      need to screen and monitor this constellation of symptoms.

PMID- 27037557
TI  - Prediction of pediatric meningioma recurrence by preoperative MRI assessment.
AB  - Preoperative identification of high-recurrent pediatric meningiomas with MRI
      features would help clinicians to make optimal treatment strategies; however, the
      relationships between radiological features and recurrence of meningiomas in
      pediatric population have not been clearly demonstrated yet. The aim of this
      study is to identify preoperative MRI features which are significant risk factors
      for recurrence of pediatric meningiomas. From January 2005 to December 2012, we
      retrospectively reviewed 52 pediatric meningiomas in terms of preoperative MRI
      features and their clinical data and followed them up from 22 to 128 months (mean
      63 months) after the initial surgery. The relationships between these
      radiological findings and relapse-free survival (RFS) time were assessed
      initially with univariate Cox analysis and then corrected by multivariate Cox
      analysis. According to univariate analysis, irregular shape, narrow-based
      attachment, and skull base location were significantly correlated with shorter
      time to recurrences of meningiomas in pediatric patients. When corrected by
      multivariate analysis, irregular shape (P = 0.05; OR 3.442, 95 % CI 1.001-11.831)
      and narrow-based attachment (P = 0.004; OR 7.164, 95 % CI 1.894-27.09) were
      strong independent predictive factors for worse RFS of pediatric meningiomas. In
      pediatric population, narrow-based attachment and irregular shape were
      significantly correlated with recurrences of meningiomas. Our results could help
      clinicians to make optimal therapeutic strategies for pediatric patients with
      intracranial meningiomas before surgery. 

PMID- 27037558
TI  - KIR3DL2 (CD158k) is a potential therapeutic target in primary cutaneous
      anaplastic large-cell lymphoma.
AB  - BACKGROUND: KIR3DL2, an inhibitory receptor expressed by natural killer cells and
      a subset of normal CD8(+) T cells, is aberrantly expressed in neoplastic cells in
      transformed mycosis fungoides and Sezary syndrome. Anti-KIR3DL2 targeted antibody
      therapy has shown potent activity in preclinical models for these diseases.
      OBJECTIVES: To examine the expression of KIR3DL2 and its potential use as a
      therapeutic target in patients with primary cutaneous anaplastic large-cell
      lymphoma (pcALCL), the most aggressive cutaneous CD30(+) lymphoproliferative
      disease. METHODS: Samples from 11 patients with pcALCL and three CD30(+)
      lymphoproliferative disease cell lines - Mac1, Mac2a and Mac2b - were used in
      KIR3DL2 expression studies using immunohistochemistry, flow cytometry and reverse
      transcriptase quantitative polymerase chain reaction. The effect of IPH4102, a
      monoclonal humanized IgG1 targeting KIR3DL2, was assessed by in vitro
      cytotoxicity assays against Mac1, Mac2a and Mac2b using allogeneic peripheral
      blood mononuclear cells as effectors. RESULTS: KIR3DL2 mRNA and protein were
      found in all human samples of pcALCL, and in the Mac2a and Mac2b cell lines.
      KIR3DL2 protein expression was present on 85.8 +/- 14.0% of CD30(+) skin
      infiltrating tumour cells. In vitro functional studies showed that KIR3DL2(+)
      Mac2a and Mac2b pcALCL lines are sensitive to antibody-derived cytotoxicity
      mediated by IPH4102, through activation of natural killer cells, in a
      concentration-dependent manner. CONCLUSIONS: pcALCL tumour cells express KIR3DL2,
      and we provide preclinical proof of concept for the use of IPH4102, a humanized
      anti-KIR3DL2 antibody, to treat patients with primary cutaneous CD30(+) ALCL.

PMID- 27037559
TI  - The Uncontrolled Sialylation is Related to Chemoresistant Metastatic Breast
      Cancer.
AB  - Among the scientific communities, there is a convergence of results supporting a
      direct relationship between dysregulated sialylation and poor prognosis in many
      human cancers. For this reason, we have retrospectively investigated 169 cases of
      invasive ductal carcinoma of the breast, coming from female patients aged between
      31 and 76 years old. The whole series was subdivided into two prognostic groups:
      the first group consisted of 138 patients, who showed a post-treatment survival
      time more than 5 years, while the second group was made up by 31 patients, died
      within 5 years despite of chemotherapy. All the surgical specimens were fixed in
      10 % neutral buffered formalin, paraffin embedded and, then, submitted to
      routinely haematoxylin/eosin staining and to a further histochemical (Alcian
      Blue, DDD-Fast Blue B, Mercury Orange), immunohistochemical (ST3GAL5
      sialyltransferase, Ki67, c-erbB2, ER, PR) and chemico-elemental characterization.
      In the 31 cases of breast cancer belonging to the second group, an overexpression
      of sialomucins and sialyltransferases has been detected. Our results lead us to
      support that in aggressive chemoresistant breast cancers, the altered expression
      of sialic acid, due to an uncontrolled sialylation, creates an excessive negative
      charge on cell membranes, which stimulates repulsion between neoplastic cells and
      their subsequent access into the blood stream. This event implies an early
      metastatization and a rapid disease progression with fatal outcome. The early
      application of Alcian Blue stain on diagnostic biopsies of breast cancer is able
      to cheaply reveal the sialomucin accumulations, providing for the disease course.

PMID- 27037560
TI  - A test of the size-constraint hypothesis for a limit to sexual dimorphism in
      plants.
AB  - In flowering plants, many dioecious species display a certain degree of sexual
      dimorphism in non-reproductive traits, but this dimorphism tends to be much less
      striking than that found in animals. Sexual size dimorphism in plants may be
      limited because competition for light in crowded environments so strongly
      penalises small plants. The idea that competition for light constrains the
      evolution of strong sexual size dimorphism in plants (the size-constraint
      hypothesis) implies a strong dependency of the expression of sexual size
      dimorphism on the neighbouring density as a result of the capacity of plants to
      adjust their reproductive effort and investment in growth in response to their
      local environment. Here, we tested this hypothesis by experimentally altering the
      context of competition for light among male-female pairs of the light-demanding
      dioecious annual plant Mercurialis annua. We found that males were smaller than
      females across all treatments, but sexual size dimorphism was diminished for
      pairs grown at higher densities. This result is consistent with the size
      constraint hypothesis. We discuss our results in terms of the tension between
      selection on size acting in opposite directions on males and females, which have
      different optima under sexual selection, and stabilizing selection for similar
      sizes in males and females, which have similar optima under viability selection
      for plasticity in size expression under different density conditions.

PMID- 27037561
TI  - Should women with incontinence and prolapse do abdominal curls?
AB  - INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) and pelvic organ prolapse
      (POP) occur in 30-50 % of women. It is proposed that increases in intra-abdominal
      pressure (IAP) caused by high-intensity activities may contribute to symptoms of
      pelvic floor dysfunction. There is a lack of consensus as to the type of activity
      restrictions that may be necessary in this population. The objective was to
      determine the change in IAP (cm H20) during abdominal curl and cough in patients
      with UI and POP attending urodynamic evaluation. METHODS: In this exploratory
      descriptive study, 30 women with diagnosed POP and/or UI were recruited. IAP was
      measured by multichannel cystometry whilst participants performed three abdominal
      curls and three maximal coughs. RESULTS: Participants were aged 29-80 (mean 56.2)
      years, and mean +/- standard deviation (SD) body mass index (BMI) was 29.9 (5.2)
      kg/m(-2). All participants had UI and 12 had POP in addition to UI. IAP increased
      significantly from rest to abdominal curl and cough (19.6-50.3 and 78.4,
      respectively; p < 0.001). Greater pressures were generated in the women with POP
      than in those with UI only (p = 0.02). There were large variations in change in
      pressure between participants (1.67-159.66 for cough; 4-81.67 for abdominal
      curl). CONCLUSION: The large variability in IAP generated during abdominal curl
      and cough suggests some current recommendations may be unnecessarily restrictive
      in some women but important in others. Advice for women with pelvic floor
      dysfunction undertaking tasks that increase IAP needs to be individualized.

PMID- 27037562
TI  - Reliability and validity of a Turkish version of the Global Pelvic Floor Bother
      Questionnaire.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to translate the Global
      Pelvic Floor Bother Questionnaire (GPFBQ) into Turkish and to assess its validity
      and reliability. METHODS: The Turkish adaptation of the GPFBQ was created by
      following the stages of the intercultural adaptation process. A test-retest
      interval of 1 week was used to assess the reliability, which was examined by the
      intraclass correlation coefficient. The validity of the GPFBQ was assessed and
      compared with the Pelvic Floor Distress Inventory-20 (PFDI-20) and the Pelvic
      Floor Impact Questionnaire-7 (PFIQ-7) using Spearman's rank correlation
      coefficients. For construct validity, confirmatory factor analysis was performed.
      RESULTS: A total of 131 women, whose mean age was 46.83 years, were included in
      the study. The test-retest reliability of the GPFBQ was excellent (0.998, p <
      0.0001). The GPFBQ correlated significantly with the PFDI-20 (r = 0.860, p =
      0.00) and PFIQ-7 (r = 0.802, p = 0.00). Confirmatory factor analysis was
      performed to determine construct validity, and it was found that it had four
      dimensions. CONCLUSIONS: The Turkish version of the GPFBQ is a valid and reliable
      tool for assessing the symptoms of bother and severity in Turkish-speaking women
      with pelvic floor dysfunction.

PMID- 27037563
TI  - Comparison of the efficacy of tension-free vaginal tape obturator (TVT-O) and
      single-incision tension-free vaginal tape (AjustTM) in the treatment of female
      stress urinary incontinence: a 1-year follow-up randomized trial.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the efficacy of
      the tension-free vaginal tape obturator (TVT-O) and single-incision tension-free
      vaginal tape (AjustTM) in the treatment of stress urinary incontinence in a
      randomized two-arm study with a 1-year follow-up. METHODS: This single-centre
      randomized trial compared the objective and subjective cure rates of TVT-O and
      Ajust using objective criteria (cough test) and subjective criteria
      (International Consultation on Incontinence Questionnaire short form, ICIQ-UI
      SF). The objective cure rate was defined as the number of patients with a
      negative cough stress test. Subjective cure was defined as no stress leakage of
      urine after surgery based on the ICIQ-UI SF. The primary outcome was to establish
      differences in objective and subjective cure rates between the TVT-O and Ajust
      groups. We also compared postoperative pain profiles using a visual analogue
      scale (VAS), improvement in quality of life using the ICIQ- UI SF and the
      Incontinence Quality of Life questionnaire, and overall satisfaction with the
      surgical procedure using a VAS and a five-item Likert scale. Inclusion criteria
      were age over 18 years, signed informed consent, and urodynamic stress urinary
      incontinence. Following a power calculation, 50 patients were enrolled into each
      group (Ajust and TVT-O). RESULTS: The mean follow-up after surgery was 445 days
      (SD 157.6 days) in the TVT-O group and 451.8 days (SD 127.6 days) in the Ajust
      group (p = 76.6 %). At 1 year, 47 patients were evaluated in the TVT-O group and
      49 in the Ajust group. No differences in subjective cure rates or objective cure
      rates were observed. In the Ajust and TVT-O groups, the rates for no subjective
      stress leakage were 89.8 % and 91.5 %, respectively (p = 1.0, OR 1.22, 95 % CI
      0.24 - 6.58), and the rates for a negative stress test were 89.8 % and 87.2 %,
      respectively (p = 0.76, OR 0.77, 95 % CI 0.17 - 3.32). In the Ajust group two
      patients reported de novo pain during sexual intercourse. CONCLUSIONS: After a 1
      year-follow-up, no significant differences were found with regard to subjective
      and objective outcomes between the single-incision tape Ajust and TVT-O.

PMID- 27037564
TI  - Internet Training Resulted in Improved Trainee Performance in a Simulated Opioid
      Poisoned Patient as Measured by Checklist.
AB  - INTRODUCTION: Opioid overdose is a leading cause of death in the USA. Internet
      based teaching can improve medical knowledge among trainees, but there are
      limited data to show the effect of Internet-based teaching on clinical competence
      in medical training, including management of opioid poisoning. METHODS: We used
      an ecological design to assess the effect of an Internet-based teaching module on
      the management of a simulated opioid-poisoned patient. We enrolled two
      consecutive classes of post-graduate year-1 residents from a single emergency
      medicine program. The first group (RA) was instructed to read a toxicology
      textbook chapter and the second group (IT) took a brief Internet training module.
      All participants subsequently managed a simulated opioid-poisoned patient. The
      participants' performance was evaluated with two types of checklist (simple and
      time-weighted), along with global assessment scores. RESULTS: Internet-trained
      participants performed better on both checklist scales. The difference between
      mean simple checklist scores by the IT and RA groups was 0.23 (95 % CI, 0.016
      0.44). The difference between mean time-weighted checklist scores was 0.27 (95 %
      CI, 0.048-0.49). When measured by global assessment, there was no statistically
      significant difference between RA and IT participants. CONCLUSION: These data
      suggest that the Internet module taught basic principles of management of the
      opioid-poisoned patient. In this scenario, global assessment and checklist
      assessment may not measure the same proficiencies. These encouraging results are
      not sufficient to show that this Internet tool improves clinical performance. We
      should assess the impact of the Internet module on performance in a true clinical
      environment.

PMID- 27037565
TI  - Fifty Sixth Annual Meeting of the Irish Otorhinolaryngology/Head and Neck
      Society.

PMID- 27037566
TI  - The potential diagnostic value of vitreous humor analyses at autopsy is not
      appreciated.

PMID- 27037567
TI  - Different materials for direct pulp capping: systematic review and meta-analysis
      and trial sequential analysis.
AB  - OBJECTIVES: We systematically assessed randomized controlled trials comparing
      direct pulp capping materials. METHODS: Trials comparing materials for direct
      capping and evaluating clinically and/or radiographically determined success
      after minimum 3 months were included. Two reviewers independently screened
      electronic databases (Medline, Central, Embase) and performed hand searches. Risk
      of bias was assessed and meta-analyses were performed, separated for dentition.
      Trial sequential analysis was used to assess risk of random errors. Strength of
      evidence was graded using the GRADE approach. RESULTS: From a total of 453
      identified studies, 11 (all with high risk of bias) investigating 1094 teeth (922
      patients) were included. Six studies were on primary teeth (all with carious
      exposures) and five on permanent teeth (carious and artificial exposures). Mean
      follow-up was 14 months (range 3-24). Most studies used calcium hydroxide as
      control, comparing it to mineral trioxide aggregate (MTA) (three studies),
      bonding without prior etching/conditioning (two), or bonding with prior
      etching/conditioning, enamel matrix proteins, resin-modified glass ionomer
      cement, calcium sulfate, zinc oxide eugenol, corticosteroids, antibiotics, or
      formocresol (each in only one study). One study compared MTA and calcium-enriched
      cement. In permanent teeth, risk of failure was significantly decreased if MTA
      instead of calcium hydroxide was used (risk ratio (RR) [95 % confidence intervals
      (CI)] 0.59 [0.39/0.90]); no difference was found for primary teeth. Other
      comparisons did not find significant differences or were supported by only one
      study. No firm evidence was reached according to trial sequential analysis.
      CONCLUSION: There is insufficient data to recommend or refute the use of a
      specific material. More long-term practice-based studies with real-life exposures
      are required. CLINICAL RELEVANCE: To reduce risk of failure, dentists might
      consider using MTA instead of calcium hydroxide (CH) for direct capping. Current
      evidence is insufficient for definitive recommendations.

PMID- 27037568
TI  - Location of the extraosseous and intraosseous arterial anastomosis of the
      maxillary sinus in edentulous specimens.
AB  - OBJECTIVES: The aim of this anatomical study was to measure the distance from the
      intraosseous and extraosseous arterial anastomoses of the maxillary sinus to the
      alveolar ridge in edentulous specimens dissected from human cadavers. MATERIALS
      AND METHODS: Forty edentulous maxillary specimens were dissected, anatomically
      prepared, and injected for a better visualization of the maxillary sinus artery.
      RESULTS: This study showed that the mean distance from the alveolar ridge to the
      extraosseous anastomosis was 16 mm for the second maxillary molar, 12 mm for the
      first maxillary molar, and 13 mm for the second maxillary premolar. For the
      intraosseous anastomosis to the alveolar ridge, the mean distance was 17 mm for
      the second maxillary molar, 13 mm for the first maxillary molar, and 14 mm for
      the second maxillary premolar. CONCLUSIONS: Under the conditions of this study,
      we found that the mean distance from the alveolar crest to the extraosseous
      anastomosis and intraosseous anastomosis was shortest for the first maxillary
      molar and second maxillary premolar and greatest for the second maxillary molar.
      CLINICAL RELEVANCE: These findings provide data whose relevance for clinical
      dentistry is that they can be applied to minimize the risk of damage to the
      arterial network of the maxillary sinus during surgical procedures in this
      region.

PMID- 27037569
TI  - Streptococcus mitis and Gemella haemolysans were simultaneously found in
      atherosclerotic and oral plaques of elderly without periodontitis-a pilot study.
AB  - OBJECTIVES: Local infections may contribute to the initiation and progression of
      several clinical diseases in humans. Atherosclerotic plaques of subjects
      suffering from periodontitis are colonized by periopathogens; however, the
      presence of bacteria in atherosclerotic plaques in patients without severe forms
      of periodontitis is of high relevance for the general population. MATERIALS AND
      METHODS: Patients who were electively treated for atherosclerotic lesions of the
      carotid artery and without clinical signs of periodontitis were eligible for the
      study. Oral and atherosclerotic plaques were sampled, processed, and analyzed for
      their microbial composition by 454-sequencing. RESULTS: Seventeen patients were
      included in the analyses, and 76 % of all atherosclerotic plaque specimens were
      positive for bacterial DNA. In the oral plaques, 76,532 sequences were identified
      representing 1 phylum, 17 classes, 112 families, and 263 genera. In
      atherosclerotic plaques, 6112 sequences representing 1 phylum, 4 classes, 8
      families, and 36 genera were found. The bacterial DNAs of the species Gemella
      haemolysans and Streptococcus mitis were simultaneously found in atherosclerotic
      as well as oral plaque samples of 3 patients. CONCLUSIONS: These results
      indicated that in subjects without periodontitis, the transmission of oral
      bacteria to atherosclerotic plaques of the carotid artery is a feasible event.
      CLINICAL RELEVANCE: The prevention of transient bacteremia from the oral cavity
      requires high levels of oral health.

PMID- 27037570
TI  - Cranio-maxillofacial reconstruction with microvascular radialis flaps-parameters
      and correlations of postoperative pain management.
AB  - OBJECTIVES: Postoperative pain management is of highest interest for patients
      undergoing maxillofacial surgery including microvascular reconstructive surgery.
      Currently, there is a lack of information regarding process and outcome of
      postoperative pain management after microvascular reconstruction. MATERIALS AND
      METHODS: In a prospective clinical study, 31 adults were evaluated on the first
      postoperative day following microvascular reconstruction with a radial forearm
      flap using the standardized questionnaire of the Germany-wide project Quality
      Improvement in Postoperative Pain Management (QUIPS). It enables a standardized
      assessment of patients' characteristics, pain parameters, outcome and pain
      therapy process parameters. RESULTS: Pain management consisted predominately of
      premedication with midazolam, sufentanil and metamizol intraoperatively,
      piritramid in the intensive care unit and metamizol, tramadol and fentanyl
      patches on ward. Nineteen patients (61.3 %) showed inadequate pain management
      with pain levels >=4. Among other significant relations, patients exhibiting an
      age below the median presented significant higher levels of pain under strain (p
      = .041) and maximum pain (p = .006) as well as rate of breathing (p = .009) and
      mood (p = .006) disturbance. Performance of pain counselling showed specific
      impact on pain under strain (p = .008), maximum pain (p = .004) and satisfaction
      with pain intensity (p = .001). Whether microvascular reconstruction was
      performed with primary or secondary intention or performance of a neck dissection
      did not show significant influence. CONCLUSIONS: QUIPS helped us to adequately
      evaluate the procedure-specific quality of postoperative management following
      microvascular reconstruction with a radial forearm flap. It helped us to identify
      a surprisingly high amount of inadequate pain management. Postoperative pain
      levels seem to be primarily influenced by the performed reconstruction. CLINICAL
      RELEVANCE: Establishment of a continuous and procedure-specific evaluation of
      postoperative pain levels should help to avoid inadequate pain management, which
      is widely prevalent according to the literature and our study. Preoperative pain
      counselling is essential and should be procedure specific to be its best.

PMID- 27037571
TI  - Selection of physiological spermatozoa during intracytoplasmic sperm injection.
AB  - Sperm genomic integrity has a significant effect on intracytoplasmic sperm
      injection (ICSI) outcomes, especially post-implantation. Spermatozoa selected
      based on motility and morphology do not guarantee the genomic integrity of
      spermatozoa. Nearly fifty percentage of spermatozoa in infertile men with normal
      morphology present different degrees of DNA fragmentation. However, capacitated
      or hyperactivated spermatozoa show lower degrees of DNA fragmentation. Therefore,
      selection of hyperactivated spermatozoa may improve ICSI outcome. Routinely, for
      ICSI, fast-moving spermatozoa with A or B motility pattern are mainly selected
      for injection. The result of this study shows that in processed semen samples,
      hyperactivated spermatozoa are mainly observed in B motility pattern while, in
      viscous medium like polyvinylpyrrolidone (PVP), hyperactivated spermatozoa are
      mainly present in spermatozoa with C pattern of motility (nonprogressive).
      Therefore, we propose spermatozoa with C motility pattern which contains the main
      population of physiological or hyperactivated spermatozoa should be selected for
      ICSI.

PMID- 27037572
TI  - Parent-Child Interaction, Self-Regulation, and Obesity Prevention in Early
      Childhood.
AB  - This paper describes the epidemiologic evidence linking parent-child
      relationships, self-regulation, and weight status with a focus on early
      childhood. The emotional quality of parent-child interactions may influence
      children's risk for obesity through multiple pathways. Prospective studies
      linking observer ratings of young children's self-regulation, particularly
      inhibitory control, to future weight status are discussed. Although findings are
      preliminary, promoting positive relationships between parents/caregivers and
      young children holds promise as a component of efforts to prevent childhood
      obesity. Multi-disciplinary collaborations between researchers with training in
      developmental science and child health should be encouraged. 

PMID- 27037573
TI  - IgA/IgM responses to tryptophan and tryptophan catabolites (TRYCATs) are
      differently associated with prenatal depression, physio-somatic symptoms at the
      end of term and premenstrual syndrome.
AB  - There is some evidence that lowered tryptophan and an activated tryptophan
      catabolite (TRYCAT) pathway play a role in depression, somatoform disorder, and
      postpartum blues. The aim of this study is to delineate the associations between
      the TRYCAT pathway and premenstrual syndrome (PMS) and perinatal depressive and
      physio-somatic symptoms. We examine the associations between end of term serum
      IgM and IgA responses to tryptophan and 9 TRYCATs in relation to zinc, C-reactive
      protein (CRP), and haptoglobin and prenatal physio-somatic (previously known as
      psychosomatic) symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation)
      and prenatal and postnatal depression and anxiety symptoms as measured using the
      Edinburgh Postnatal Depression Scale (EPDS), Hamilton Depression Rating Scale
      (HAMD), and Spielberger's State Anxiety Inventory (STAI). We included pregnant
      females with (n = 24) and without depression (n = 25) and 24 non-pregnant
      females. There were no significant associations between the IgA/IgM responses to
      tryptophan and TRYCATs and prenatal and postnatal depression/anxiety symptoms,
      except for lowered IgA responses to anthranilic acid in prenatal depression. A
      large part of the variance in IgA responses to most TRYCATs was explained by PMS
      and haptoglobin (positively) and CRP (inversely) levels. The IgA responses to
      TRYCATs were significantly increased in PMS, in particular picolinic,
      anthranilic, xanthurenic and kynurenic acid, and 3OH-kynurenine. Variance (62.5%)
      in physio-somatic symptoms at the end of term was explained by PMS, previous
      depressions, zinc (inversely), CRP and haptoglobin (both positively), and the IgM
      responses to quinolinic acid (positively), anthranilic acid, and tryptophan (both
      negatively). The results suggest that mucosa-derived TRYCAT pathway activation is
      significantly associated with PMS, but not with perinatal depression/anxiety
      symptoms. Physio-somatic symptoms in pregnancy have an immune-inflammatory
      pathophysiology. Induction of the TRYCAT pathway appears to be more related to
      physio-somatic than to depression symptoms.

PMID- 27037574
TI  - Aqueous Leaf Extract of Withania somnifera as a Potential Neuroprotective Agent
      in Sleep-deprived Rats: a Mechanistic Study.
AB  - Modern lifestyle and sustained stress of professional commitments in the current
      societal set up often disrupts the normal sleep cycle and duration which is known
      to lead to cognitive impairments. In the present study, we report whether leaf
      extract of Withania somnifera (Ashwagandha) has potential neuroprotective role in
      acute stress of sleep deprivation. Experiments were performed on three groups of
      adult Wistar rats: group 1 (vehicle treated-undisturbed sleep [VUD]), group 2
      (vehicle treated-sleep deprived [VSD]), and group 3 (ASH-WEX treated-sleep
      deprived [WSD]). Groups 1 and 2 received single oral feeding of vehicle and group
      3 received ASH-WEX orally (140 mg/kg or 1 ml/250 g of body weight) for 15
      consecutive days. Immediately after this regimen, animals from group 1 were
      allowed undisturbed sleep (between 6 a.m. and 6 p.m.), whereas rats of groups 2
      and 3 were deprived of sleep during this period. We observed that WSD rats showed
      significant improvement in their performance in behavioral tests as compared to
      VSD group. At the molecular level, VSD rats showed acute change in the expression
      of proteins involved in synaptic plasticity, cell survival, and apoptosis in the
      hippocampus region of brain, which was suppressed by ASH-WEX treatment thus
      indicating decreased cellular stress and apoptosis in WSD group. This data
      suggest that Ashwagandha may be a potential agent to suppress the acute effects
      of sleep loss on learning and memory impairments and may emerge as a novel
      supplement to control SD-induced cognitive impairments.

PMID- 27037575
TI  - C9ORF72 Regulates Stress Granule Formation and Its Deficiency Impairs Stress
      Granule Assembly, Hypersensitizing Cells to Stress.
AB  - Hexanucleotide repeat expansions in the C9ORF72 gene are causally associated with
      frontotemporal lobar dementia (FTLD) and/or amyotrophic lateral sclerosis (ALS).
      The physiological function of the normal C9ORF72 protein remains unclear. In this
      study, we characterized the subcellular localization of C9ORF72 to processing
      bodies (P-bodies) and its recruitment to stress granules (SGs) upon stress
      related stimuli. Gain of function and loss of function experiments revealed that
      the long isoform of C9ORF72 protein regulates SG assembly. CRISPR/Cas9-mediated
      knockdown of C9ORF72 completely abolished SG formation, negatively impacted the
      expression of SG-associated proteins such as TIA-1 and HuR, and accelerated cell
      death. Loss of C9ORF72 expression further compromised cellular recovery responses
      after the removal of stress. Additionally, mimicking the pathogenic condition via
      the expression of hexanucleotide expansion upstream of C9ORF72 impaired the
      expression of the C9ORF72 protein, caused an abnormal accumulation of RNA foci,
      and led to the spontaneous formation of SGs. Our study identifies a novel
      function for normal C9ORF72 in SG assembly and sheds light into how the mutant
      expansions might impair SG formation and cellular-stress-related adaptive
      responses.

PMID- 27037576
TI  - Physical Characterization and Innate Immunogenicity of Aggregated Intravenous
      Immunoglobulin (IGIV) in an In Vitro Cell-Based Model.
AB  - PURPOSE: To investigate in vitro the innate immune response to accelerated stress
      induced aggregates of intravenous immunoglobulin (IGIV) using a well-defined
      human cell-line model, and to correlate the innate response to physical
      properties of the aggregates. METHODS: IGIV aggregates were prepared by applying
      various accelerated stress methods, and particle size, count and structure were
      characterized. Immune cell activation as tracked by inflammatory cytokines
      released in response to aggregates was evaluated in vitro using peripheral blood
      mononuclear cells (PBMC), primary monocytes and immortalized human monocyte-like
      cell lines. RESULTS: IGIV aggregates produced by mechanical stress induced higher
      cytokine release by PBMC and primary monocytes than aggregates formed by other
      stresses. Results with the monocytic cell line THP-1 paralleled trends in PBMC
      and primary monocytes. Effects were dose-dependent, enhanced by complement
      opsonization, and partially inhibited by blocking toll-like receptors (TLR2 and
      TLR4) and to a lesser extent by blocking Fc gamma receptors (FcgammaRs).
      CONCLUSIONS: Stress-induced IGIV aggregates stimulate a dose-dependent cytokine
      response in human monocytes and THP-1 cells, mediated in part by TLRs, FcgammaRs
      and complement opsonization. THP-1 cells resemble primary monocytes in many
      respects with regard to tracking the innate response to IgG aggregates.
      Accordingly, the measurement of inflammatory cytokines released by THP-1 cells
      provides a readily accessible assay system to screen for the potential innate
      immunogenicity of IgG aggregates. The results also highlight the role of
      aggregate structure in interacting with the different receptors mediating innate
      immunity.

PMID- 27037578
TI  - Large Particle Sorting to Isolate Live Parasitic Nematode Eggs.
AB  - Traditional jet-in-air cell sorters have been designed and optimized to isolate
      small particles such as mammalian lymphocytes with an average diameter of 10 MUm.
      We discuss the practical considerations of setting up a conventional jet-in-air
      cell sorter, using a 200-MUm nozzle, to isolate the large parasitic nematode eggs
      of Nippostrongylus brasiliensis, with a maximum size of 60 MUm. The eggs were
      separated based on light scattering properties, no fluorescent dye or molecule
      was required.

PMID- 27037579
TI  - Measurement of Low-Abundance Intracellular mRNA Using Amplified FISH Staining and
      Image-Based Flow Cytometry.
AB  - Recent advances in instrument design and reagent development have enabled the
      rapid progression in available measurement techniques in the field of flow
      cytometry. In particular, image-based flow cytometry extends the analysis
      capacity found in traditional flow cytometry. Until recently, it was not possible
      to measure intracellular mRNA in specific phenotypes of cells by flow cytometry.
      In this protocol, a method of completing simultaneous intracellular measurement
      of mRNA and protein for PPAR-gamma in peripheral blood monocytes, which have been
      exposed in vitro to modified LDL, is described. The process of PPAR-gamma
      activation following uptake of modified LDL is believed to play a role in the
      development of atherogenesis. PPAR-gamma mRNA measurement was made possible using
      an amplified FISH technique (PrimeFlow RNA Assay) that allowed for detection of
      low-abundant intracellular mRNA expression. This protocol represents a continued
      effort by the authors' laboratory to establish and validate new techniques to
      assess the role of the immune system in chronic disease.

PMID- 27037577
TI  - Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal
      Functioning: Clinical Implications.
AB  - BACKGROUND: The fronto-striatal circuits are the common neurobiological basis for
      neuropsychiatric disorders, including schizophrenia, Parkinson's disease,
      Huntington's disease, attention deficit hyperactivity disorder, obsessive
      compulsive disorder, and Tourette's syndrome. Fronto-striatal circuits consist of
      motor circuits, associative circuits, and limbic circuits. All circuits share 2
      common features. First, all fronto-striatal circuits consist of hyper direct,
      direct, and indirect pathways. Second, all fronto-striatal circuits are modulated
      by dopamine. Intracellularly, the effect of dopamine is largely mediated through
      the cyclic adenosine monophosphate/protein kinase A signaling cascade with an
      additional role for the cyclic guanosine monophosphate/protein kinase G pathway,
      both of which can be regulated by phosphodiesterases. Phosphodiesterases are thus
      a potential target for pharmacological intervention in neuropsychiatric disorders
      related to dopaminergic regulation of fronto-striatal circuits. METHODS: Clinical
      studies of the effects of different phosphodiesterase inhibitors on cognition,
      affect, and motor function in relation to the fronto-striatal circuits are
      reviewed. RESULTS: Several selective phosphodiesterase inhibitors have positive
      effects on cognition, affect, and motor function in relation to the fronto
      striatal circuits. CONCLUSION: Increased understanding of the subcellular
      localization and unraveling of the signalosome concept of phosphodiesterases
      including its function and dysfunction in the fronto-striatal circuits will
      contribute to the design of new specific inhibitors and enhance the potential of
      phosphodiesterase inhibitors as therapeutics in fronto-striatal circuits.

PMID- 27037580
TI  - Relevance of flow cytometric enumeration of post-thaw leucocytes: influence of
      temperature during cell staining on viable cell recovery.
AB  - BACKGROUND AND OBJECTIVES: Our post-thaw cell recovery rates differed
      substantially in interlaboratory comparisons of identical samples, potentially
      due to different temperatures during cell staining. MATERIALS AND METHODS: Viable
      CD34(+) cells and leucocyte (WBC) subtypes were quantified by multiparameter
      single-platform flow cytometry in leucapheresis products collected from 30 adult
      lymphoma and myeloma patients, and from 10 paediatric patients. After thawing,
      cells were prepared for analysis within 30 min between thawing and acquisition,
      at either 4 degrees C or at room temperature. RESULTS: For cell products
      cryopreserved in conventional freezing medium (10% final DMSO), viable cell
      recovery was clearly lower after staining at 4 degrees C than at RT. Of all WBC
      subtypes analysed, CD4(+) T cells showed the lowest median recovery of 4% (4
      degrees C) vs. 25% (RT), followed by CD3, CD34 and CD8 cells. The recovery was
      highest for CD3gammadelta cells with 44% (4 degrees C) vs. 71% (RT). In the 10
      samples cryopreserved in synthetic freezing medium (5% final DMSO), median
      recovery rates were 89% for viable CD34 (both at 4 degrees C and RT) and 79% (4
      degrees C) vs 68% (RT) for WBC. CONCLUSIONS: The post-thaw environment and,
      potentially, the cryoprotectant impact the outcome of cell enumeration, and
      results from the analysis tube may not be representative of the cells infused
      into a patient.

PMID- 27037581
TI  - Nuclear DNA level and life cycle of kelps: Evidence for sex-specific polyteny in
      Macrocystis (Laminariales, Phaeophyceae).
AB  - Giant kelp, Macrocystis pyrifera (Linnaeus) C. Agardh, is the subject of intense
      breeding studies for marine biomass production and conservation of natural
      resources. In this context, six gametophyte pairs and a sporophyte offspring of
      Macrocystis from South America were analyzed by flow cytometry. Minimum relative
      DNA content per cell (1C) was found in five males. Unexpectedly, nuclei of all
      female gametophytes contained approximately double the DNA content (2C) of males;
      the male gametophyte from one locality also contained 2C, likely a spontaneous
      natural diploid variant. The results illustrate a sex-specific difference in
      nuclear DNA content among Macrocystis gametophytes, with the chromosomes of the
      females in a polytenic condition. This correlates with significantly larger cell
      sizes in female gametophytes compared to males and resource allocation in
      oogamous reproduction. The results provide key information for the interpretation
      of DNA measurements in kelp life cycle stages and prompt further research on the
      regulation of the cell cycle, metabolic activity, sex determination, and
      sporophyte development. 

PMID- 27037582
TI  - Aragonite infill in overgrown conceptacles of coralline Lithothamnion spp.
      (Hapalidiaceae, Hapalidiales, Rhodophyta): new insights in biomineralization and
      phylomineralogy.
AB  - New empirical and quantitative data in the study of calcium carbonate
      biomineralization and an expanded coralline psbA framework for phylomineralogy
      are provided for crustose coralline red algae. Scanning electron microscopy (SEM)
      and energy dispersive spectrometry (SEM-EDS) pinpointed the exact location of
      calcium carbonate crystals within overgrown reproductive conceptacles in
      rhodolith-forming Lithothamnion species from the Gulf of Mexico and Pacific
      Panama. SEM-EDS and X-ray diffraction (XRD) analysis confirmed the elemental
      composition of these calcium carbonate crystals to be aragonite. After spore
      release, reproductive conceptacles apparently became overgrown by new vegetative
      growth, a strategy that may aid in sealing the empty conceptacle chamber, hence
      influencing the chemistry of the microenvironment and in turn promoting aragonite
      crystal growth. The possible relevance of various types of calcium carbonate
      polymorphs present in the complex internal structure and skeleton of crustose
      corallines is discussed. This is the first study to link SEM, SEM-EDS, XRD,
      Microtomography and X-ray microscopy data of aragonite infill in coralline algae
      with phylomineralogy. The study contributes to the growing body of literature
      characterizing and speculating about how the relative abundances of carbonate
      biominerals in corallines may vary in response to changes in atmospheric pCO2 ,
      ocean acidification, and global warming. 

PMID- 27037583
TI  - A quantitative real-time PCR assay for identification and enumeration of the
      occasionally co-occurring ichthyotoxic Pseudochattonella farcimen and P.
      verruculosa (Dictyochophyceae) and analysis of variation in gene copy numbers
      during the growth phase of single and mixed cultures.
AB  - The ichthyotoxic genus Pseudochattonella forms recurrent extensive blooms in
      coastal waters in Japan, New Zealand and Northern Europe. It comprises of two
      morphologically similar species, P. verruculosa and P. farcimen, which
      complicates visual species identification and enumeration of live and fixed
      material. Primers designed previously could not quantitatively distinguish
      species in mixed assemblages. To address this issue we developed two primer sets:
      one revealed itself to be genus specific for Pseudochattonella and the other
      species-specific for P. verruculosa. By subtracting cell estimates for P.
      verruculosa from combined results we could calculate cell numbers for P.
      farcimen. This approach has overcome the challenges posed by the very limited
      sequence availability and low gene variability between the two species. The qPCR
      assay was extensively tested for specificity, efficiency and sensitivity over an
      entire growth cycle in both single and mixed assemblages. Comparison of cell
      abundance estimates obtained by qPCR assay and microscopy showed no statistically
      significant difference until stationary and death phases. The assay was also
      tested on environmental samples collected during a small Pseudochattonella bloom
      in Denmark in March-April 2015. It was impossible to distinguish P. farcimen and
      P. verruculosa by light microscopy but qPCR showed both species were present. The
      two methods provided nearly identical cell numbers but the assay provided
      discrimination and enumeration of both species. 

PMID- 27037584
TI  - Pseudo-nitzschia arctica sp. nov., a new cold-water cryptic Pseudo-nitzschia
      species within the P. pseudodelicatissima complex.
AB  - A new nontoxic Pseudo-nitzschia species belonging to the P. pseudodelicatissima
      complex, P. arctica, was isolated from different areas of the Arctic. The
      erection of P. arctica is mainly supported by molecular data, since the species
      shares identical ultrastructure with another species in the complex, P.
      fryxelliana, and represents a new case of crypticity within the genus. Despite
      their morphological similarity, the two species are not closely related in
      phylogenies based on LSU, ITS and rbcL. Interestingly, P. arctica is
      phylogenetically most closely related to P. granii and P. subcurvata, from which
      the species is, however, morphologically different. P. granii and P. subcurvata
      lack the central larger interspace which is one of the defining features of the
      P. pseudodelicatissima complex. The close genetic relationship between P. arctica
      and the two species P. granii and P. subcurvata is demonstrated by analysis of
      the secondary structure of ITS2 which revealed no compensatory base changes, two
      hemi-compensatory base changes, and two deletions in P. arctica with respect to
      the other two species. These findings emphasize that rates of morphological
      differentiation, molecular evolution and speciation are often incongruent for
      Pseudo-nitzschia species, resulting in a restricted phylogenetic value for
      taxonomic characters used to discriminate species. The description of a new
      cryptic species, widely distributed in the Arctic and potentially representing an
      endemic component of the Arctic diatom flora, reinforces the idea of the
      existence of noncosmopolitan Pseudo-nitzschia species and highlights the need for
      combined morphological and molecular analyses to assess the distributional
      patterns of phytoplankton species. 

PMID- 27037585
TI  - Potential distribution of the invasive freshwater dinoflagellate Ceratium
      furcoides (Levander) Langhans (Dinophyta) in South America.
AB  - Dinoflagellates of the genus Ceratium are predominantly found in marine
      environments, with a few species in inland waters. Over the last decades, the
      freshwater species Ceratium hirundinella and Ceratium furcoides have colonized
      and invaded several South American basins. The purpose of this study was to
      create a distribution model for the invasive dinoflagellate C. furcoides in South
      America in order to further investigate the basins at potential risk, as well as
      the environmental conditions that influence its expansion. This species is known
      to develop blooms due to its mobility, resistance to sedimentation, and optimized
      use of resources. Although nontoxic, blooms of the species cause many problems to
      both the natural ecosystems and water users. Potential distribution was predicted
      by using a maximum entropy algorithm (MaxEnt). Model was run with 101 occurrences
      obtained from the scientific literature, and climatic, hydrological and
      topographic variables. The developed model had a very good performance for the
      study area. The most susceptible areas identified were mainly concentrated in the
      basins between southeastern Brazil and northeastern Argentina. Besides already
      affected regions, new potentially suitable areas were identified in temperate
      regions of South America. The information generated here will be useful for
      authorities responsible for water and watershed management to monitor the spread
      of this species and address problems related to its establishment in new
      environments. 

PMID- 27037586
TI  - Swimming patterns of the quadriflagellate Tetraflagellochloris mauritanica
      (Chlamydomonadales, Chlorophyceae).
AB  - Chlamydomonadales are elective subjects for the investigation of the problems
      related to locomotion and transport in biological fluid dynamics, whose
      resolution could enhance searching efficiency and assist in the avoidance of
      dangerous environments. In this paper, we elucidate the swimming behavior of
      Tetraflagellochloris mauritanica, a unicellular-multicellular alga belonging to
      the order Chlamydomonadales. This quadriflagellate alga has a complex swimming
      motion consisting of alternating swimming phases connected by in-place random
      reorientations and resting phases. It is capable of both forward and backward
      swimming, both being normal modes of swimming. The complex swimming behavior
      resembles the run-and-tumble motion of peritrichous bacteria, with in-place
      reorientation taking the place of tumbles. In the forward swimming, T.
      mauritanica shows a very efficient flagellar beat, with undulatory retrograde
      waves that run along the flagella to their tip. In the backward swimming, the
      flagella show a nonstereotypical synchronization mode, with a pattern that does
      not fit any of the modes present in the other Chlamydomonadales so far
      investigated. 

PMID- 27037587
TI  - Rickettsial endosymbiont in the "early-diverging" streptophyte green alga
      Mesostigma viride.
AB  - A bacterial endosymbiont was unexpectedly found in the "axenic" culture strain of
      the streptophyte green alga Mesostigma viride (NIES-995). Phylogenetic analyses
      based on 16S rRNA gene sequences showed that the symbiont belongs to the order
      Rickettsiales, specifically to the recently designated clade "Candidatus
      Megaira," which is closely related to the well-known Rickettsia clade.
      Rickettsiales bacteria of the "Ca. Megaira" clade are found in a taxonomically
      diverse array of eukaryotic hosts, including chlorophycean green algae, several
      ciliate species, and invertebrates such as Hydra. Transmission electron
      microscopy, fluorescence in situ hybridi-zation, and SYBR Green I staining
      experiments revealed that the endosymbiont of M. viride NIES-995 is rod shaped,
      typically occurs in clusters, and is surrounded by a halo-like structure,
      presumably formed by secretory substances from the bacterium. Two additional M.
      viride strains (NIES-296 and NIES-475), but not SAG50-1, were found to house the
      rickettsial endosymbiont. Analyses of strain NIES-995 transcriptome data
      indicated the presence of at least 91 transcriptionally active genes of symbiont
      origins. These include genes for surface proteins (e.g., rOmpB) that are known to
      play key roles in bacterial attachment onto host eukaryotes in related Rickettsia
      species. The assembled M. viride transcriptome includes transcripts that code for
      a suite of predicted algal-derived proteins, such as Ku70, WASH, SCAR, and CDC42,
      which may be important in the formation of the algal-rickettsial association. 

PMID- 27037588
TI  - Effects of temperature and salinity on the growth of Alexandrium (Dinophyceae)
      isolates from the Salish Sea.
AB  - Toxin-producing blooms of dinoflagellates in the genus Alexandrium have plagued
      the inhabitants of the Salish Sea for centuries. Yet the environmental conditions
      that promote accelerated growth of this organism, a producer of paralytic
      shellfish toxins, is lacking. This study quantitatively determined the growth
      response of two Alexandrium isolates to a range of temperatures and salinities,
      factors that will strongly respond to future climate change scenarios. An
      empirical equation, derived from observed growth rates describing the temperature
      and salinity dependence of growth, was used to hindcast bloom risk. Hindcasting
      was achieved by comparing predicted growth rates, calculated from in situ
      temperature and salinity data from Quartermaster Harbor, with corresponding
      Alexandrium cell counts and shellfish toxin data. The greatest bloom risk,
      defined at MU >0.25 d(-1) , generally occurred from April through November
      annually; however, growth rates rarely fell below 0.10 d(-1) . Except for a few
      occasions, Alexandrium cells were only observed during the periods of highest
      bloom risk and paralytic shellfish toxins above the regulatory limit always fell
      within the periods of predicted bloom occurrence. While acknowledging that
      Alexandrium growth rates are affected by other abiotic and biotic factors, such
      as grazing pressure and nutrient availability, the use of this empirical growth
      function to predict higher risk time frames for blooms and toxic shellfish within
      the Salish Sea provides the groundwork for a more comprehensive biological model
      of Alexandrium bloom dynamics in the region and will enhance our ability to
      forecast blooms in the Salish Sea under future climate change scenarios. 

PMID- 27037589
TI  - Energy cost and putative benefits of cellular mechanisms modulating buoyancy in
      aflagellate marine phytoplankton.
AB  - Little information is available on the energetics of buoyancy modulation in
      aflagellate phytoplankton, which comprises the majority of autotrophic cells
      found in the ocean. Here, we computed for three aflagellate species of marine
      phytoplankton (Emiliania huxleyi, Thalassiosira pseudonana, and Ethmodiscus rex)
      the theoretical minimum energy cost as photons absorbed and nitrogen resource
      required of the key physiological mechanisms (i.e., replacement of quaternary
      ammonium by dimethyl-sulfoniopropionate, storage of polysaccharides, and cell
      wall biosynthesis) affecting the cell's vertical movement as a function of
      nitrogen (N) availability. These energy costs were also normalized to the
      capacity of each buoyancy mechanism to modulate sinking or rising rates based on
      Stokes' law. The three physiological mechanisms could act as ballast in the three
      species tested in conditions of low N availability at a low fraction (<12%) of
      the total photon energy cost for growth. Cell wall formation in E. huxleyi was
      the least costly ballast strategy, whereas in T. pseudonana, the photon energy
      cost of the three ballast strategies was similar. In E. rex, carbohydrate storage
      and mobilization appear to be energetically cheaper than modulations in organic
      solute synthesis to achieve vertical migration. This supports the carbohydrate
      ballast strategy for vertical migration for this species, but argues against the
      theory of replacement of low- or high-density organic solutes. This study brings
      new insights into the energy cost and potential selective advantages of several
      strategies modulating the buoyancy of aflagellate marine phytoplankton. 

PMID- 27037590
TI  - The color of mass culture: spectral characteristics of a shallow water column
      through shade-limited algal growth dynamics(1).
AB  - It is envisioned that mass algal cultivation for commercial biofuels production
      will entail the use of large raceway pond systems, which typically have shade
      limited photosynthetic growth within depths of 20-30 cm. The attenuation of light
      and spectral qualities of red, green, and blue wavelengths in a 20-cm water
      column as a function of Chl-a concentration during exponential and linear phases
      of growth dynamics for the marine diatom Thalassiosira pseudonana was examined
      under laboratory conditions. While photosynthetically available radiation (PAR)
      was in excess throughout the water column during the phase of exponential growth,
      PAR became rate limiting differently for red, green, and blue wavelengths during
      the phase of linear growth. The transition from exponential to linear growth
      occurred at 1-2 mg Chl-a . L-1, whereby a scalar ~5 MUmol photons . m-2 . s-1 at
      20-cm depth was found to occur as would be anticipated having the compensation
      point for where rates of photosynthesis and respiration are equal. During the
      phase of linear growth, red wavelengths became increasingly dominant at depth as
      Chl-a concentrations increased, being contrary to the optical conditions for
      those natural bodies of water that forced the evolution of phytoplankton
      photosynthesis. It is hypothesized this dramatic difference in water column
      optics between natural and synthetic environments could influence a variety of
      biological reactions, importantly non-photochemical quenching capacities, which
      could negatively impact crop yield. 

PMID- 27037591
TI  - Short- and long-term acclimation patterns of the giant kelp Macrocystis pyrifera
      (Laminariales, Phaeophyceae) along a depth gradient.
AB  - The giant kelp, Macrocystis pyrifera, is exposed to highly variable irradiance
      and temperature regimes across its geographic and vertical depth gradients. The
      objective of this study was to extend our understanding of algal acclimation
      strategies on different temporal scales to those varying abiotic conditions at
      various water depths. Different acclimation strategies to various water depths
      (0.2 and 4 m) between different sampling times (Jan/Feb and Aug/Sept 2012; long
      term acclimation) and more rapid adjustments to different depths (0.2, 2 and 4 m;
      short-term acclimation) during 14 d of transplantation were found. Adjustments of
      variable Chl a fluorescence, pigment composition (Chl c, fucoxanthin), and the de
      epoxidation state of the xanthophyll cycle pigments were responsible for the
      development of different physiological states with respect to various solar
      radiation and temperature climates. Interestingly, the results indicated that
      phlorotannins are important during long-term acclimation while antioxidants have
      a crucial role during short-term acclimation. Furthermore, the results suggested
      that modifications in total lipids and fatty acid compositions apparently also
      might play a role in depth acclimation. In Aug/Sept (austral winter), M. pyrifera
      responded to the transplantation from 4 m to 0.2 m depth with a rise in the
      degree of saturation and a switch from shorter- to longer-chain fatty acids.
      These changes seem to be essential for the readjustment of thylakoid membranes
      and might, thus, facilitate efficient photosynthesis under changing irradiances
      and temperatures. Further experiments are needed to disentangle the relative
      contribution of solar radiation, temperature and also other abiotic parameters in
      the observed physiological changes. 

PMID- 27037592
TI  - Molecular markers define progressing stages of phosphorus limitation in the
      nitrogen-fixing cyanobacterium, Crocosphaera.
AB  - Crocosphaera watsonii is a marine cyanobacterium that frequently inhabits low
      phosphate environments in oligotrophic oceans. While C. watsonii has the ability
      to fix atmospheric nitrogen, its growth may be limited by availability of
      phosphorus. Biomarkers that indicate cellular phosphorus status give insight into
      how P-limitation can affect the distribution of nitrogen-fixing cyanobacterial
      populations. However, adaptation to phosphorus stress is complex and one marker
      may not be sufficient to determine when an organism is P-limited. In this study,
      we characterized the transcription of key genes, activated during phosphorus
      stress in C. watsonii WH8501, to determine how transcription changed during the
      phosphorus stress response. Transcription of pstS, which encodes a high-affinity
      phosphate binding protein, was discovered to be quickly up-regulated in
      phosphorus-depleted cells as an immediate stress response; however, its
      transcription declined after a period of phosphorus starvation. In addition, diel
      regulation of pstS in C. watsonii WH8501 complicates the interpretation of this
      marker in field applications. Transcription of the gene coding for the arsenite
      efflux protein, arsB, was upregulated after pstS in phosphorus limited cells, but
      it remained upregulated at later stages of phosphorus limitation. These results
      demonstrate that a single molecular marker does not adequately represent the
      entire phosphorus stress response in C. watsonii WH8501. Using both markers, the
      variations in transcriptional response over a range of degrees of phosphorus
      limitation may be a better approach for defining cellular phosphorus status. 

PMID- 27037593
TI  - Taxonomic revision of Chlamydomonas subg. Amphichloris (Volvocales,
      Chlorophyceae), with resurrection of the genus Dangeardinia and descriptions of
      Ixipapillifera gen. nov. and Rhysamphichloris gen. nov.
AB  - Chlamydomonas (Cd.) is one of the largest but most polyphyletic genera of
      freshwater unicellular green algae. It consists of 400-600 morphological species
      and requires taxonomic revision. Toward reclassification, each morphologically
      defined classical subgenus (or subgroup) should be examined using culture
      strains. Chlamydomonas subg. Amphichloris is characterized by a central nucleus
      between two axial pyrenoids, however, the phylogenetic structure of this subgenus
      has yet to be examined using molecular data. Here, we examined 12 strains
      including six newly isolated strains, morphologically identified as Chlamydomonas
      subg. Amphichloris, using 18S rRNA gene phylogeny, light microscopy, and
      mitochondria fluorescent microscopy. Molecular phylogenetic analyses revealed
      three independent lineages of the subgenus, separated from the type species of
      Chlamydomonas, Cd. reinhardtii. These three lineages were further distinguished
      from each other by light and fluorescent microscopy-in particular by the
      morphology of the papillae, chloroplast surface, stigmata, and mitochondria-and
      are here assigned to three genera: Dangeardinia emend., Ixipapillifera gen. nov.,
      and Rhysamphichloris gen. nov. Based on the molecular and morphological data, two
      to three species were recognized in each genus, including one new species, I.
      pauromitos. In addition, Cd. deasonii, which was previously assigned to subgroup
      "Pleiochloris," was included in the genus Ixipapillifera as I. deasonii comb.
      nov. 

PMID- 27037594
TI  - Resolving the phylogenetic relationship between Chlamydomonas sp. UWO 241 and
      Chlamydomonas raudensis sag 49.72 (Chlorophyceae) with nuclear and plastid DNA
      sequences.
AB  - The Antarctic psychrophilic green alga Chlamy-domonas sp. UWO 241 is an emerging
      model for studying microbial adaptation to polar environments. However, little is
      known about its evolutionary history and its phylogenetic relationship with other
      chlamydomonadalean algae is equivocal. Here, we attempt to clarify the
      phylogenetic position of UWO 241, specifically with respect to Chlamydomonas rau
      densis SAG 49.72. Contrary to a previous report, we show that UWO 241 is a
      distinct species from SAG 49.72. Our phylogenetic analyses of nuclear and plastid
      DNA sequences reveal that UWO 241 represents a unique lineage within the
      Moewusinia clade (sensu Nakada) of the Chlamydomonadales (Chlorophyceae,
      Chlorophyta), closely affiliated to the marine species Chlamydomonas parkeae SAG
      24.89. 

PMID- 27037595
TI  - Mixotrophy in the terrestrial green alga Apatococcus lobatus (Trebouxiophyceae,
      Chlorophyta).
AB  - The green microalga Apatococcus lobatus is widely distributed in terrestrial
      habitats throughout many climatic zones. It dominates green biofilms on natural
      and artificial substrata in temperate latitudes and is regarded as a key genus of
      obligate terrestrial consortia. Until now, its isolation, cultivation and
      application as a terrestrial model organism has been hampered by slow growth
      rates and low growth capacities. A mixotrophic culturing approach clearly
      enhanced the accumulation of biomass, thereby permitting the future application
      of A. lobatus in different types of bio-assays necessary for material and biofilm
      research. The ability of A. lobatus to grow mixotrophically is assumed as a
      competitive advantage in terrestrial habitats. 

PMID- 27037596
TI  - Corrigendum.

PMID- 27037597
TI  - Corrigendum.

PMID- 27037598
TI  - Differential Role of Neurohypophysial Hormones in Hypotension and Nitric Oxide
      Production During Endotoxaemia.
AB  - Besides their well-established endocrine roles, vasopressin and oxytocin are also
      important regulators of immune function, participating in a complex
      neuroendocrine-immune network. In the present study, we investigated whether and
      how vasopressin and oxytocin could modulate lipopolysaccharide (LPS)-induced
      nitric oxide (NO) production in a well-established model of experimental
      endotoxaemia. Male Wistar rats were previously treated i.v. with vasopressin V1
      or oxytocin receptor antagonists and then received either an i.v. LPS injection
      to induce endotoxaemia or a saline imjection as a control. The animals were
      divided into two groups: in the first group, blood was collected at 2, 4 and 6 h
      after LPS injection; in the second group, mean arterial blood pressure (MABP) and
      heart rate (HR) were recorded over 6 h. Plasma vasopressin and oxytocin values
      were higher in LPS- compared to saline-injected animals at 2 and 4 h but returned
      to basal levels at 6 h. NO levels exhibited an opposite pattern, showing a
      progressive increase over the entire period. The previous administration of a
      vasopressin V1 receptor antagonist significantly reduced NO plasma concentrations
      at 2 and 4 h but not at 6 h. By contrast, oxytocin receptor agonist pre-treatment
      had no effect on the NO plasma concentration. In relation to MABP, previous
      treatment with vasopressin V1 receptor antagonist reversed the LPS-induced
      hypotension at 4 h, although this was not the case for oxytocin antagonist
      treated animals. None of the antagonists affected HR. Our findings indicate that
      vasopressin (but not oxytocin) has effects on NO production during endotoxaemia
      in rats, although they do not lend support to the proposed anti-inflammatory
      actions of vasopressin during endotoxaemia.

PMID- 27037599
TI  - Associations between respiratory arrhythmia and fundamental frequency of
      spontaneous crying in preterm and term infants at term-equivalent age.
AB  - This study investigated whether lower vagal function in preterm infants is
      associated with increased fundamental frequency (F0 ; frequency of vocal fold
      vibration) of their spontaneous cries. We assessed respiratory sinus arrhythmia
      (RSA) during quiet sleep as a measure of vagal function, and its relationship
      with the F0 of spontaneous cries in healthy preterm and term infants at term
      equivalent age. The results showed that preterm infants have significantly lower
      RSA, and higher overall F0 than term infants. Moreover, lower RSA was associated
      with higher overall F0 in preterm infants, whereas higher RSA was positively
      associated with mean and maximum F0 , and a larger F0 range in term infants.
      These results suggest that individual differences in vagal function may be
      associated with the F0 of spontaneous cries via modulation of vocal fold tension
      in infants at an early developmental stage. (c) 2016 The Authors. Developmental
      Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 58:724-733,
      2016.

PMID- 27037600
TI  - Testing a model of codependency for college students in Taiwan based on Bowen's
      concept of differentiation.
AB  - The purpose of this study was to test a model of codependency based on Bowen's
      concept of differentiation for college students in Taiwan. The relations between
      family-of-origin dysfunction, differentiation of self, codependency traits and
      related symptoms including low self-esteem, relationship distress and
      psychological adjustment problems were examined. Data were collected from 567
      college students from 2 large, urban universities in northern Taiwan. Results
      indicated a significantly negative relationship between levels of codependency
      and self-differentiation and that self-differentiation partially mediated the
      relationship between family-of-origin dysfunction and codependency. The
      implications of these findings for counselling Taiwanese college students who
      experience codependency traits and related symptoms as well as suggestions for
      future research are discussed.

PMID- 27037601
TI  - PCAN: Probabilistic correlation analysis of two non-normal data sets.
AB  - Most cancer research now involves one or more assays profiling various biological
      molecules, e.g., messenger RNA and micro RNA, in samples collected on the same
      individuals. The main interest with these genomic data sets lies in the
      identification of a subset of features that are active in explaining the
      dependence between platforms. To quantify the strength of the dependency between
      two variables, correlation is often preferred. However, expression data obtained
      from next-generation sequencing platforms are integer with very low counts for
      some important features. In this case, the sample Pearson correlation is not a
      valid estimate of the true correlation matrix, because the sample correlation
      estimate between two features/variables with low counts will often be close to
      zero, even when the natural parameters of the Poisson distribution are, in
      actuality, highly correlated. We propose a model-based approach to correlation
      estimation between two non-normal data sets, via a method we call Probabilistic
      Correlations ANalysis, or PCAN. PCAN takes into consideration the distributional
      assumption about both data sets and suggests that correlations estimated at the
      model natural parameter level are more appropriate than correlations estimated
      directly on the observed data. We demonstrate through a simulation study that
      PCAN outperforms other standard approaches in estimating the true correlation
      between the natural parameters. We then apply PCAN to the joint analysis of a
      microRNA (miRNA) and a messenger RNA (mRNA) expression data set from a squamous
      cell lung cancer study, finding a large number of negative correlation pairs when
      compared to the standard approaches.

PMID- 27037602
TI  - Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma
      cells by inhibiting the urokinase-plasminogen activator through modulation of the
      Akt signaling pathway.
AB  - Hispolon has been reported to possess antioxidant, antiinflammatory, and
      antitumor activities. However, the effect of hispolon on the metastasis of
      nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated
      how the antimetastatic activity and relevant signaling pathways of hispolon
      affected three NPC cell lines. The results revealed that hispolon significantly
      reduced the migration and invasion of three NPC cells in a dose-dependent manner
      from 0 to 50 uM. Hispolon also significantly inhibited the activity and
      expression of urokinase-plasminogen activator (uPA) as well as the
      phosphorylation of Akt. Moreover, blocking the Akt pathway also enhanced the
      antimetastatic ability of hispolon in the NPC cells. In conclusion, hispolon
      inhibited uPA expression and NPC cell metastasis by downregulating Akt signal
      pathways; therefore, hispolon exerts beneficial effects in chemoprevention. (c)
      2016 Wiley Periodicals, Inc. Environ Toxicol 32: 645-655, 2017.

PMID- 27037603
TI  - Formation Mechanism of the First Carbon-Carbon Bond and the First Olefin in the
      Methanol Conversion into Hydrocarbons.
AB  - The elementary reactions leading to the formation of the first carbon-carbon bond
      during early stages of the zeolite-catalyzed methanol conversion into
      hydrocarbons were identified by combining kinetics, spectroscopy, and DFT
      calculations. The first intermediates containing a C-C bond are acetic acid and
      methyl acetate, which are formed through carbonylation of methanol or dimethyl
      ether even in presence of water. A series of acid-catalyzed reactions including
      acetylation, decarboxylation, aldol condensation, and cracking convert those
      intermediates into a mixture of surface bounded hydrocarbons, the hydrocarbon
      pool, as well as into the first olefin leaving the catalyst. This carbonylation
      based mechanism has an energy barrier of 80 kJ mol(-1) for the formation of the
      first C-C bond, in line with a broad range of experiments, and significantly
      lower than the barriers associated with earlier proposed mechanisms.

PMID- 27037604
TI  - A genes eye view of ontogeny: de novo assembly and profiling of the Gryllus
      rubens transcriptome.
AB  - Crickets (Orthoptera:Gryllidae) are widely used model organisms for
      developmental, evolutionary, neurobiological and behavioural research. Here, we
      developed a de novo transcriptome from pooled RNA-seq Illumina data spanning
      seven stages in the life cycle of Gryllus rubens. Approximately 705 Mbp of data
      was assembled and filtered to form 27 312 transcripts. We were able to annotate
      52% of our transcripts using BLAST and assign at least one gene ontology term to
      41%. Pooled samples from three different ontogenetic stages were used for
      transcriptomic profiling revealing patterns of differential gene expression that
      highlight processes in the different life stages. Embryonic and early instar
      development was enriched for ecdysteroid metabolism, cytochrome P450s and
      glutathione production. Late instar development was enriched for regulation of
      gene expression and many of the genes highly expressed during this stage were
      involved in conserved developmental signalling pathways suggesting that these
      developmental pathways are active beyond embryonic development. Adults were
      enriched for fat transport (mostly relating to egg production) and production of
      octopamine, an important neurohormone. We also identified genes involved in
      conserved developmental pathways (Hedgehog, Hippo, Wnt, JAK/STAT, TGF-beta,
      Notch, and MEK/ERK). This is the first transcriptome spanning ontogeny in Gryllus
      rubens and a valuable resource for future work on development and evolution in
      Orthoptera.

PMID- 27037605
TI  - Compatible stability study of panax notoginseng saponin injection
      (xueshuantong(r)) in combination with 47 different injectables.
AB  - Panax Notoginseng Saponin (PNS) injection (Xueshuantong(r), XST) plays an
      important role in acute and chronic treatment of cardiovascular disease in China.
      XST, a freeze-dried powder injection of PNS, contains ginsenosides, Rg1, Rb1, Re,
      Rd. and notoginsenoside, R1. Study of the stability of herbal medicine injections
      is limited. The degradation products may contribute to adverse drug reactions
      (ADRs). The stability kinetics and degradation mechanisms of the five ingredients
      of PNS in XST injection were systematically explored in aqueous solution. The
      compatible stability of XST injection in combination with 47 injectables was
      evaluated using biophysical analysis. A principal components analysis model
      provided a good clustering result after compatibility. The degradation of the
      five ingredients in aqueous solution was found to be acid, temperature, oxidation
      and trivalent ion-dependent. All ingredients were much more stable in XST
      injection than in aqueous solutions. Nine degradation products were identified by
      adopting LC-Q-TOF/MS. Standards exceeding the osmotic pressure and/or particle
      size were found to be the probable causes of the ADR, which were related to drug
      combination. To minimize the risk of ADRs, drug combinations should be avoided
      until the complicated chemical matrices of the Chinese medicine injections are
      more clearly understood. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27037606
TI  - Controlled degradation pattern of hydroxyapatite/calcium carbonate composite
      microspheres.
AB  - Hydroxyapatite (HAP) is widely used in clinic due to its good biocompatibility
      and osteoconductivity except for its slow degradation speed. In the present
      study, spherical calcium carbonate (CaCO3 ) is fabricated in the presence of silk
      protein sericin, which is transmuted into HAP microsphere in phosphate solution
      with the assistance of microwave irradiation. The effect of reaction conditions
      on the conversion of CaCO3 is investigated including reaction time, chemical
      composition of phosphate solution, and microwave power to get a series of
      HAP/CaCO3 composites. The degradation property of the composites is evaluated in
      vitro. Results show the degradation speed of the composite with higher HAP
      content is slower. The degradation rate of the composite could be changed
      effectively by modulating the proportion of HAP and CaCO3 . This work provides a
      feasible method for the preparation of spherical HAP/CaCO3 composite with
      controllable degradability. The composite thus obtained may be an ideal material
      for bone tissue engineering application. Microsc. Res. Tech. 79:518-524, 2016.
      (c) 2016 Wiley Periodicals, Inc. 

PMID- 27037607
TI  - Multiple pulmonary embolisms in a male marathon athlete: Is intense endurance
      exercise a real thrombogenic risk?
AB  - Intense endurance exercise could be associated with multiple thrombogenic risk
      factors, including dehydration, hemoconcentration, inflammation, and injuries.
      Despite an increasing number of reported cases of deep venous thrombosis (DVT) in
      athletes that is raising awareness in the medical community, the prevalence is
      not well established and evidenced-based guidelines for management of this
      clinical scenario are lacking. We present an episode of unprovoked DVT and
      multiple pulmonary embolisms with severe right ventricular dysfunction in a male
      runner. We highlight the challenge of diagnosing DVT and pulmonary embolism in
      athletes due to frequently atypical symptomatology and the emergent need for
      longitudinal studies to evaluate their thrombogenic risk and develop specific
      guidelines in this field.

PMID- 27037608
TI  - Instrumental and Sensory Texture Attributes of High-Protein Nutrition Bars
      Formulated with Extruded Milk Protein Concentrate.
AB  - Previous instrumental study of high-protein nutrition (HPN) bars formulated with
      extruded milk protein concentrate (MPC) indicated slower hardening compared to
      bars formulated with unmodified MPC. However, hardness, and its change during
      storage, insufficiently characterizes HPN bar texture. In this study, MPC80 was
      extruded at 2 different conditions and model HPN bars were prepared. A trained
      sensory panel and instrumental techniques were used to measure HPN bar firmness,
      crumbliness, fracturability, hardness, cohesiveness, and other attributes to
      characterize texture change during storage. Extrusion modification, storage
      temperature, and storage time significantly affected the instrumental and sensory
      panel measured texture attributes. The HPN bars became firmer and less cohesive
      during storage. When evaluated at the same storage conditions, the texture
      attributes of the HPN bars formulated with the different extrudates did not
      differ significantly from each other. However, textural differences were noted
      most of the time between the control and the HPN bars formulated with extruded
      MPC80. An adapted HPN bar crumbliness measurement technique produced results that
      were correlated with sensory panel measured crumbliness (r = 0.85) and
      cohesiveness (r = -0.84). Overall, the HPN bars formulated with extruded MPC80
      were significantly softer, less crumbly, and more cohesive than the control
      during storage. 

PMID- 27037609
TI  - Doubly robust survival trees.
AB  - Estimating a patient's mortality risk is important in making treatment decisions.
      Survival trees are a useful tool and employ recursive partitioning to separate
      patients into different risk groups. Existing 'loss based' recursive partitioning
      procedures that would be used in the absence of censoring have previously been
      extended to the setting of right censored outcomes using inverse probability
      censoring weighted estimators of loss functions. In this paper, we propose new
      'doubly robust' extensions of these loss estimators motivated by semiparametric
      efficiency theory for missing data that better utilize available data.
      Simulations and a data analysis demonstrate strong performance of the doubly
      robust survival trees compared with previously used methods. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27037610
TI  - Conservation of sex chromosomes in lacertid lizards.
AB  - Sex chromosomes are believed to be stable in endotherms, but young and
      evolutionary unstable in most ectothermic vertebrates. Within lacertids, the
      widely radiated lizard group, sex chromosomes have been reported to vary in
      morphology and heterochromatinization, which may suggest turnovers during the
      evolution of the group. We compared the partial gene content of the Z-specific
      part of sex chromosomes across major lineages of lacertids and discovered a
      strong evolutionary stability of sex chromosomes. We can conclude that the common
      ancestor of lacertids, living around 70 million years ago (Mya), already had the
      same highly differentiated sex chromosomes. Molecular data demonstrating an
      evolutionary conservation of sex chromosomes have also been documented for
      iguanas and caenophidian snakes. It seems that differences in the evolutionary
      conservation of sex chromosomes in vertebrates do not reflect the distinction
      between endotherms and ectotherms, but rather between amniotes and anamniotes, or
      generally, the differences in the life history of particular lineages. 

PMID- 27037611
TI  - Sharp acoustic boundaries across an altitudinal avian hybrid zone despite
      asymmetric introgression.
AB  - Birdsong is a sexually selected trait that could play an important evolutionary
      role when related taxa come into secondary contact. Many songbird species,
      however, learn their songs through copying one or more tutors, which complicates
      the evolutionary outcome of such contact. Two subspecies of a presumed vocal
      learner, the grey-breasted wood-wren (Henicorhina leucophrys), replace each other
      altitudinally across the western slope of the Ecuadorian Andes. These subspecies
      are morphologically very similar, but show striking differences in their song. We
      examined variation in acoustic traits and genetic composition across the
      altitudinal range covered by both subspecies and between two allopatric
      populations. The acoustic boundary between the subspecies was found to be highly
      abrupt across a narrow elevational range with virtually no evidence of song
      convergence. Mixed singing and use of hetero-subspecific song occurred in the
      contact zone and was biased towards the use of leucophrys song types. Hetero
      subspecific song copying by hilaris and not by leucophrys reflected a previously
      found asymmetric pattern of response to song playback. Using amplified fragment
      length polymorphisms (AFLP) markers, we detected hybridization in the contact
      zone and asymmetric introgression in parapatric populations, with more leucophrys
      alleles present in hilaris populations than vice versa. This pattern may be a
      trail of introgression due to upslope displacement of leucophrys by hilaris. Our
      data suggest that song learning may impact speciation and hybridization in
      contrasting ways at different spatial scales: although learning may speed up
      population divergence in songs, thereby enhancing assortative mating and reducing
      gene flow, it may at a local level also lead to the copying of heterospecific
      songs, therefore allowing some level of hybridization and introgression.

PMID- 27037612
TI  - The post-2015 landscape: vested interests, corporate social responsibility and
      public health advocacy.
AB  - This paper explores the tensions between UN calls for private sector engagement
      in the post-2015 landscape and public health opposition to those 'harm
      industries' that are 'corporate vectors of disease' for the mounting global non
      communicable disease burden. The UN's support for public-private partnership has
      provided industries with 'vested interests' in the propagation of unhealthy
      behaviours with new opportunities for the strategic alignment of their corporate
      social responsibility (CSR) endeavours with the post-2015 sustainable development
      agenda. This has galvanised public health advocates to place pressure on the
      World Health Organisation to formalise their ambiguous stance towards private
      sector involvement in public policy formation and the resultant 'conflicts of
      interest'. This paper critically examines the 'gathering storm' between this
      'anti-corporate movement' and the alcohol industry in the increasingly
      politicised domain of CSR. Drawing on the example of SABMiller's Tavern
      Intervention Program, the paper argues that CSR represents a profound threat to
      the sanctity and moral authority of the public health worldview. Questions
      therefore need to be asked about whether the public health-led path of industry
      non-association will necessarily result in health improvements or just a further
      retrenchment of the ideological faultlines explored in the paper.

PMID- 27037613
TI  - An essential role of caffeoyl shikimate esterase in monolignol biosynthesis in
      Medicago truncatula.
AB  - Biochemical and genetic analyses have previously identified caffeoyl shikimate
      esterase (CSE) as an enzyme in the monolignol biosynthesis pathway in Arabidopsis
      thaliana, although the generality of this finding has been questioned. Here we
      show the presence of CSE genes and associated enzyme activity in barrel medic
      (Medicago truncatula, dicot, Leguminosae), poplar (Populus deltoides, dicot,
      Salicaceae), and switchgrass (Panicum virgatum, monocot, Poaceae). Loss of
      function of CSE in transposon insertion lines of M. truncatula results in severe
      dwarfing, altered development, reduction in lignin content, and preferential
      accumulation of hydroxyphenyl units in lignin, indicating that the CSE enzyme is
      critical for normal lignification in this species. However, the model grass
      Brachypodium distachyon and corn (Zea mays) do not possess orthologs of the
      currently characterized CSE genes, and crude protein extracts from stems of these
      species exhibit only a weak esterase activity with caffeoyl shikimate. Our
      results suggest that the reaction catalyzed by CSE may not be essential for
      lignification in all plant species.

PMID- 27037614
TI  - Comparison of IgG concentrations by radial immunodiffusion, electrophoretic gamma
      globulin concentrations and total globulins in neonatal foals.
AB  - REASONS FOR PERFORMING STUDY: Failure of transfer of passive immunity (FTPI) in
      foals is associated with a risk of infection and death. The current diagnostic
      gold standard is quantification of immunoglobulins using radial immunodiffusion
      (IgG-RID). Routine diagnosis is often performed using semi-quantitative tests.
      Concentrations of serum electrophoretic gamma globulins (EGG) and total globulins
      may be useful to assess FTPI, but few studies have investigated their use.
      OBJECTIVES: To assess agreement between IgG-RID and EGG and evaluate the accuracy
      of total globulin concentration to diagnose FTPI based on both IgG-RID and EGG.
      STUDY DESIGN: Prospective study. METHODS: A total of 360 serum samples were
      harvested at 6-24 h post natum from 60 German Warmblood foals. Concentrations of
      EGG, IgG-RID and total globulin (calculated from total proteins and albumin) were
      measured. Agreement between EGG and IgG-RID was assessed using Bland-Altman plots
      and Passing-Bablok regression. The accuracy of total globulin concentration was
      assessed using rank correlation and ROC curve analysis. RESULTS: Good agreement
      was found with slightly lower EGG than IgG-RID concentrations (Bland-Altman
      systemic bias -1.9 g/l) which was more pronounced at higher concentrations
      (regression equation: IgG-RID = -0.78 + 1.28 * EGG). Correlations between total
      globulin concentration and EGG and total globulin concentration and IgG-RID were
      0.93 and 0.79, respectively. The area under the curve was 0.982 and 0.952 for EGG
      <4 and <8 g/l and 0.953 and 0.899 for IgG-RID <4 and <8 g/l. Sensitivities and
      specificities of total globulin concentration in the diagnosis of FTPI were
      comparable to those of commonly used screening tests, but cut-offs could be
      selected to achieve sensitivities of >95% with 71.2% (IgG-RID) and 90.5% (EGG)
      specificity for <4 g/l and >90% with 66.0% (IgG-RID) and 87.9% (EGG) specificity
      for <8 g/l. CONCLUSIONS: There is good agreement between EGG and IgG-RID, with
      slightly more conservative estimates of immunoglobulins obtained using EGG. Total
      globulins may be a useful and economic quantitative screening test with cut-offs
      achieving high sensitivities, but analyser-specific cut-offs may be necessary.

PMID- 27037615
TI  - Whole-body radiofrequency coil for (31) P MRSI at 7 T.
AB  - Widespread use of ultrahigh-field (31) P MRSI in clinical studies is hindered by
      the limited field of view and non-uniform radiofrequency (RF) field obtained from
      surface transceivers. The non-uniform RF field necessitates the use of high
      specific absorption rate (SAR)-demanding adiabatic RF pulses, limiting the signal
      to-noise ratio (SNR) per unit of time. Here, we demonstrate the feasibility of
      using a body-sized volume RF coil at 7 T, which enables uniform excitation and
      ultrafast power calibration by pick-up probes. The performance of the body coil
      is examined by bench tests, and phantom and in vivo measurements in a 7-T MRI
      scanner. The accuracy of power calibration with pick-up probes is analyzed at a
      clinical 3-T MR system with a close to identical (1) H body coil integrated at
      the MR system. Finally, we demonstrate high-quality three-dimensional (31) P MRSI
      of the human body at 7 T within 5 min of data acquisition that includes RF power
      calibration. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037616
TI  - Projected future distribution of dentists in Japan.
AB  - OBJECTIVES: Appropriate health policies for the supply of dentists have been an
      ongoing issue in many developed countries. The purpose of this study was to
      estimate the future distribution of dentists with different working statuses in
      Japan and to discuss policy implications about the supply of dentists in any
      country. METHODS: This was a retrospective cohort study using data from the
      National Survey of Physicians, Dentists and Pharmacists for 1972-2012. Based on
      data from the 2010 and 2012 surveys, we calculated by means of a Markov model the
      future number of dentists with different working statuses until 2042 according to
      sex. RESULTS: We estimated that the total number of active dentists will decrease
      from 2012 to 2042. The number of active dentists per 1,000 population was
      predicted to reach a peak in 2018, decrease by 4.2% from 2012 to 2038, and
      thereafter slightly increase. With regard to working status, the number of
      dentists with their own practices per 1,000 people was predicted to have reached
      a peak in 2014 and decrease by 22.0% until 2042. We estimated that the number of
      dentists used in dental clinics per 1,000 population will increase continuously
      between 2012 and 2042 by 20.0%. CONCLUSIONS: Our study suggests that maintaining
      this supply of dentists may lead to maldistribution of their working status in
      the future.

PMID- 27037617
TI  - Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases
      virulence in the rat caries model.
AB  - In oral biofilms, the major environmental challenges encountered by Streptococcus
      mutans are acid and oxidative stresses. Previously, we showed that the
      transcriptional regulators SpxA1 and SpxA2 are involved in general stress
      survival of S. mutans with SpxA1 playing a primary role in activation of
      antioxidant and detoxification strategies whereas SpxA2 serves as a back up
      activator of oxidative stress genes. We have also found that spxA1 mutant strains
      (?spxA1 and ?spxA1?spxA2) are outcompeted by peroxigenic oral streptococci in
      vitro and have impaired abilities to colonize the teeth of rats fed a highly
      cariogenic diet. Here, we show that the Spx proteins can also exert regulatory
      roles in the expression of additional virulence attributes of S. mutans.
      Competence activation is significantly impaired in Deltaspx strains and the
      production of mutacin IV and V is virtually abolished in DeltaspxA1 strains.
      Unexpectedly, the ?spxA2 strain showed increased production of glucans from
      sucrose, without affecting the total amount of bacteria within biofilms when
      compared with the parent strain. By using the rat caries model, we showed that
      the capacity of the DeltaspxA1 and DeltaspxA2 strains to cause caries on smooth
      tooth surfaces is significantly impaired. The ?spxA2 strain also formed fewer
      lesions on sulcal surfaces. This report reveals that global regulation via Spx
      contributes to the cariogenic potential of S. mutans and highlights that animal
      models are essential in the characterization of bacterial traits implicated in
      virulence.

PMID- 27037618
TI  - An HF exposure system for mice with improved efficiency.
AB  - An exposure system that addresses difficulties that arise for exposure of small
      animals at low frequencies with a high exposure level is presented. The system,
      intended to operate at 27 MHz, consists of two identical transverse electro
      magnetic (TEM) cells for exposure and sham exposure of groups of 16 free-running
      mice housed in pairs within standard cages, capable of exposure over extended
      daily periods while being provided food and water. Inclusion of the exposure cell
      in a half-wavelength resonator has been developed as a new paradigm to enhance
      field strength for an increase of >50-fold in available specific absorption rate
      (SAR) levels compared to traditional TEM cell configurations. The system
      described allows both daily and weekly exposure schedules and supports blinded
      protocols with continuous wave (CW) and amplitude modulation (AM) signals with
      programmable modulation depths and frequencies. Electric field (E-field)
      homogeneity across the TEM cell along a vertical plane (orthogonal to the axis of
      the TEM line) was within 3.3%, and 3.1% along the horizontal plane. Accurate and
      comprehensive dosimetric assessments based on whole-body and organ-specific SAR
      essential for in vivo bioelectromagnetic experiments are presented, which takes
      into account various factors (e.g., mouse activities, close proximity, and field
      homogeneity). Average SAR levels are controllable in the range of 1 mW/kg to 2
      W/kg, with expanded uncertainty (k = 2) of 1 dB and instantaneous variation (k =
      1) of 4 dB.

PMID- 27037619
TI  - Pre-Selection Test to Identify High Responder Donor Goats.
AB  - The aim of the study was to evaluate the feasibility of pre-selection of high or
      low responder does prior to the superovulatory protocols. Twenty Saanen does
      received 800 IU of equine chorionic gonadotropin (eCG) at the end of long-term
      progestogen treatment. Fourteen days later, a second progestogen protocol
      associated with a multiple-dose follicle stimulation hormone (FSH) treatment (5
      IU/kg of FSH, in six decreasing doses between days 4 to 6 of the protocol) was
      administered. Transrectal ultrasound was used to assess the follicular status at
      the beginning of superovulatory treatments, at the oestrous onset and on the
      seventh day of the oestrous cycle for counting corpora lutea (CL). A significant
      lower number of CL was obtained in eCG-treated in comparision with FSH-treated
      does (p < 0.05). A quartic regression was able to explain the relationship
      between the number of CL in response to both treatments (r(2) =0.50; p < 0.05).
      Seventy per cent (14 of 20) of does maintained the same ovulatory response (high
      or low) after treatments. The Kappa (kappa = 0.40; p < 0.05) and Spearman (rs =
      0.39; p = 0.08) coefficients were able to show a relationship between treatments.
      Regarding the follicular status, there is a significant relationship between the
      number of small follicles (r = 0.71; r(2) =0.47; p < 0.01) and total follicles (r
      = 0.60; p < 0.01) at eCG and first FSH dose with the number of CL. Moreover, it
      was found a negative relationship between the presence of large follicles and the
      number of CL in response to eCG treatment (r = -0.44; p < 0.05), but not from FSH
      (p > 0.05). In conclusion, the screening test with eCG has the potential to
      identify Saanen does that will better respond to the superovulatory protocol with
      FSH. In addition, it highlighted the importance of an ultrasound evaluation prior
      to the beginning of superovulatory treatments with FSH to characterize the
      follicular status and identify the potential donors of high ovulatory response in
      MOET programmes in goats. 

PMID- 27037620
TI  - Prurigo pigmentosa: a clinical and histopathological study of nine Chinese cases.
AB  - BACKGROUND: Prurigo pigmentosa (PP) is a chronic and recurrent inflammatory skin
      disease with the distinctive and prominent feature of reticulate
      hyperpigmentation. Most known cases have been reported in Japan; here we report
      nine Chinese cases. OBJECTIVE: To determine the clinical manifestation of PP and
      its effects in Chinese individuals compared with patients of other ethnicities.
      METHODS: We retrospectively analysed nine cases of PP. For all cases, clinical
      information was collected and reviewed, and skin biopsies were performed.
      Furthermore, we followed all nine patients to determine the recurrence rate.
      RESULTS: All nine patients fulfilled the diagnostic criteria of PP. The mean age
      of the patients at diagnosis was 27.4 years, and the patients were predominantly
      female. Skin lesions at different stages commonly co-occurred in the same
      patient. The most commonly affected part of the body was the back, but the armpit
      was also often involved. Patients responded well to minocycline treatment for the
      short duration of 8.62 days, and a lower recurrence rate (28.3%) was recorded
      after treatment. Biopsy revealed classic neutrophil and (or) lymphocyte
      infiltration, spongiosis, and necrotic keratocytes. Abscesses occasionally
      occurred in the follicular orifice. The abnormal presentation of hair follicles
      was also discovered. All characteristics were found to coexist in different
      stages. CONCLUSION: We conclude that PP is easy to misdiagnose. Histopathological
      characteristics can coexist at different stages, consistent with the clinical
      finding that different stages of skin lesions presented concurrently,
      contributing to misdiagnosis. Oral administration of minocycline not only yields
      an excellent response but also effectively reduces the recurrence rate.

PMID- 27037621
TI  - INHIBITION OF FATTY ACID DESATURASES IN Drosophila melanogaster LARVAE BLOCKS
      FEEDING AND DEVELOPMENTAL PROGRESSION.
AB  - Fatty acid desaturases are metabolic setscrews. To study their systemic impact on
      growth in Drosophila melanogaster, we inhibited fatty acid desaturases using the
      inhibitor CAY10566. As expected, the amount of desaturated lipids is reduced in
      larvae fed with CAY10566. These animals cease feeding soon after hatching, and
      their growth is strongly attenuated. A starvation program is not launched, but
      the expression of distinct metabolic genes is activated, possibly to mobilize
      storage material. Without attaining the normal size, inhibitor-fed larvae molt to
      the next stage indicating that the steroid hormone ecdysone triggers molting
      correctly. Nevertheless, after molting, expression of ecdysone-dependent
      regulators is not induced. While control larvae molt a second time, these larvae
      fail to do so and die after few days of straying. These effects are similar to
      those observed in experiments using larvae deficient for the fatty acid
      desaturase1 gene. Based on these data, we propose that the ratio of saturated to
      unsaturated fatty acids adjusts a sensor system that directs feeding behavior. We
      also hypothesize that loss of fatty acid desaturase activity leads to a block of
      the genetic program of development progression indirectly by switching on a
      metabolic compensation program. 

PMID- 27037622
TI  - Intraoperative colonoscopy in patients with colorectal cancer: Review of recent
      developments.
AB  - The use of intraoperative colonoscopy has increased alongside progress in the
      development of colonoscopy-associated devices and techniques, including the
      colonoscope itself. In the present review, we focus on four circumstances in
      which intraoperative colonoscopy is beneficial to colorectal surgery: (i)
      intraoperative determination of a tumor's location; (ii) observation of the
      proximal colon in cases of obstructive colorectal cancer; (iii) confirmation of
      the integrity of anastomosis; and (iv) novel surgical techniques that combine
      laparoscopic and endoscopic surgery. In light of the findings of our review, a
      combination of colonoscopy and surgery-especially laparoscopic surgery-is
      expected to facilitate the optimal handling of a variety of colorectal tumors,
      ranging from benign cases to advanced and obstructive cases. 

PMID- 27037623
TI  - Structures, Unimolecular Fragmentations, and Reactivities of the Self-Assembled
      Multimetallic/Peptide Complexes [Mnn (GlyGly-H)2n-1 ](+) and [Mnn+1 (GlyGly-H)2n
      ](2.).
AB  - Complexes of Mn(2+) with deprotonated GlyGly are investigated by sustained off
      resonance irradiation collision-induced dissociation (SORI-CID), infrared
      multiple-photon dissociation spectroscopy, ion-molecule reactions, and
      computational methods. Singly [Mnn (GlyGly-H)2n-1 ](+) and doubly [Mnn+1 (GlyGly
      H)2n ](2+) charged clusters are formed from aqueous solutions of MnCl2 and GlyGly
      by electrospray ionization. The most intense ion produced was the singly charged
      [M2 (GlyGly-H)3 ](+) cluster. Singly charged clusters show extensive
      fragmentations of small neutral molecules such as water and carbon dioxide as
      well as dissociation pathways related to the loss of NH2 CHCO and GlyGly. For the
      doubly charged clusters, however, loss of GlyGly is observed as the main
      dissociation pathway. Structure elucidation of [Mn3 (GlyGly-H)4 ](2+) clusters
      has also been done by IRMPD spectroscopy as well as DFT calculations. It is shown
      that the lowest energy structure of the [Mn3 (GlyGly-H)4 ](2+) cluster is
      deprotonated at all carboxylic acid groups and metal ions are coordinated with
      carbonyl oxygen atoms, and that all amine nitrogen atoms are hydrogen bonded to
      the amide hydrogen. A comparison of the calculated high-spin (sextet) and low
      spin (quartet) state structures of [Mn3 (GlyGly-H)4 ](2+) is provided. IRMPD
      spectroscopic results are in agreement with the lowest energy high-spin structure
      computed. Also, the gas-phase reactivity of these complexes towards neutral CO
      and water was investigated. The parent complexes did not add any water or CO,
      presumably due to saturation at the metal cation. However, once some of the
      ligand was removed via CO2 laser IRMPD, water was seen to add to the complex.
      These results are consistent with high-spin Mn(2+) complexes. 

PMID- 27037624
TI  - Disordered nucleiome: Abundance of intrinsic disorder in the DNA- and RNA-binding
      proteins in 1121 species from Eukaryota, Bacteria and Archaea.
AB  - Intrinsically disordered proteins (IDPs) are abundant in various proteomes, where
      they play numerous important roles and complement biological activities of
      ordered proteins. Among functions assigned to IDPs are interactions with nucleic
      acids. However, often, such assignments are made based on the guilty-by
      association principle. The validity of the extension of these correlations to all
      nucleic acid binding proteins has never been analyzed on a large scale across all
      domains of life. To fill this gap, we perform a comprehensive computational
      analysis of the abundance of intrinsic disorder and intrinsically disordered
      domains in nucleiomes (~548 000 nucleic acid binding proteins) of 1121 species
      from Archaea, Bacteria and Eukaryota. Nucleiome is a whole complement of proteins
      involved in interactions with nucleic acids. We show that relative to other
      proteins in the corresponding proteomes, the DNA-binding proteins have
      significantly increased disorder content and are significantly enriched in
      disordered domains in Eukaryotes but not in Archaea and Bacteria. The RNA-binding
      proteins are significantly enriched in the disordered domains in Bacteria,
      Archaea and Eukaryota, while the overall abundance of disorder in these proteins
      is significantly increased in Bacteria, Archaea, animals and fungi. The high
      abundance of disorder in nucleiomes supports the notion that the nucleic acid
      binding proteins often require intrinsic disorder for their functions and
      regulation.

PMID- 27037625
TI  - Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent
      Neurotoxicity.
AB  - Free radical damage caused by ferrous iron is involved in the pathogenesis of
      secondary brain injury after intracerebral hemorrhage (ICH). NF-E2-related factor
      2 (Nrf2), a major phase II gene regulator that binds to antioxidant response
      element, represents an important cellular cytoprotective mechanism against
      oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage
      by Fe(2+) . Therefore, we examined cytotoxicity in primary astrocytes induced by
      iron overload and evaluated the effects of Fe(2+) on Nrf2 expression. The results
      demonstrated that 24-h Fe(2+) exposure exerted time- and concentration-dependent
      cytotoxicity in astrocytes. Furthermore, Fe(2+) exposure in astrocytes resulted
      in time- and concentration-dependent increases in Nrf2 expression, which preceded
      Fe(2+) toxicity. Nrf2-specific siRNA further knocked down Nrf2 levels, resulting
      in greater Fe(2+) -induced astrocyte cytotoxicity. These data indicate that
      induction of Nrf2 expression could serve as an adaptive self-defense mechanism,
      although it is insufficient to completely protect primary astrocytes from Fe(2+) 
      induced neurotoxicity. 

PMID- 27037626
TI  - Endothelial cell dysfunction in globoid cell leukodystrophy.
AB  - Angiogenesis plays a pivotal role in the physiology and pathology of the brain.
      Microvascular alterations have been observed in various neurodegenerative
      disorders, including genetic leukodystrophies. Globoid cell leukodystrophy (GLD)
      is a lysosomal storage disease caused by beta-galactosylceramidase (GALC)
      deficiency and characterized by the accumulation of the neurotoxic metabolite
      psychosine in the central nervous system and peripheral tissues. Structural and
      functional alterations occur in the microvascular endothelium of the brain of GLD
      patients and twitcher mice, a murine model of the disease. In addition, increased
      vessel permeability and a reduced capacity to respond to proangiogenic stimuli
      characterize the endothelium of twitcher animals. On the one hand, these
      alterations may depend, at least in part, on the local and systemic angiostatic
      activity exerted by psychosine on endothelial cells. On the other hand, studies
      performed in vivo on zebrafish embryos and in vitro on human endothelial cells
      suggest that GALC downregulation may also lead to psychosine-independent neuronal
      and vascular defects. Together, experimental observations indicate that
      endothelial cell dysfunctions may represent a novel pathogenic mechanism in human
      leukodystrophies, including GLD. A better understanding of the molecular
      mechanisms responsible for these microvascular alterations may provide new
      insights for the therapy of GLD. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037628
TI  - Effect of Spacer Connecting the Secondary Electron Donor Phenothiazine in
      Subphthalocyanine-Fullerene Conjugates in Promoting Electron Transfer Followed by
      Hole Shift Process.
AB  - Sequential electron/hole transfer between energetically well-positioned entities
      of photosynthetic reaction center models is one of the commonly employed
      mechanisms to generate long-lived charge-separated states. A wealth of
      information, applicable towards light energy harvesting and building
      optoelectronic devices, has been acquired from such studies. In the present
      study, we report on the effect of spacer (direct or via phenoxy linkage)
      connecting the hole shifting agent, phenothiazine (PTZ), on photoinduced charge
      stabilization in subphthalocyanine-fullerene donor-acceptor conjugates. In these
      conjugates, the subphthalocyanine (SubPc) and fullerene (C60 ) served as primary
      electron donor and acceptor, respectively, while the phenothiazine entities act
      as hole shifting agents. The newly synthesized compounds were characterized by
      optical absorption and emission, computational, and electrochemical methods. The
      redox potentials measured using differential pulse voltammetry were used to
      estimate free-energy changes for charge separation, hole migration, and charge
      recombination processes. Using femto- and nanosecond transient absorption
      techniques, evidence for charge separation, and kinetics of charge separation and
      recombination were obtained in polar benzonitrile and nonpolar toluene solvents.
      In the conjugate where the phenothiazine entities are directly linked to SubPc,
      evidence for sequential electron transfer followed by hole shift leading to long
      lived charge separated state was weak, primarily due to the delocalization of
      HOMO on both SubPc and PTZ entities. However, in case of the conjugate where the
      PTZ and SubPc are linked via phenoxy spacers, sequential electron transfer/hole
      shift was observed leading to the formation of long-lived charge-separated
      states. The present study brings out the importance of the spacer group
      connecting the hole shifting agent in model donor-acceptor conjugates to generate
      long-lived charge-separated states.

PMID- 27037627
TI  - A novel approach for targeted elimination of CSPG4-positive triple-negative
      breast cancer cells using a MAP tau-based fusion protein.
AB  - Chondroitin sulfate proteoglycan 4 (CSPG4) has been identified as a highly
      promising target antigen for immunotherapy of triple-negative breast cancer
      (TNBC). TNBC represents a highly aggressive heterogeneous group of tumors lacking
      expression of estrogen, progesterone and human epidermal growth factor receptor
      2. TNBC is particularly prevalent among young premenopausal women. No suitable
      targeted therapies are currently available and therefore, novel agents for the
      targeted elimination of TNBC are urgently needed. Here, we present a novel
      cytolytic fusion protein (CFP), designated alphaCSPG4(scFv)-MAP, that consists of
      a high affinity CSPG4-specific single-chain antibody fragment (scFv) genetically
      fused to a functionally enhanced form of the human microtubule-associated protein
      (MAP) tau. Our data indicate that alphaCSPG4(scFv)-MAP efficiently targets
      CSPG4(+) TNBC-derived cell lines MDA-MB-231 and Hs 578T and potently inhibits
      their growth with IC50 values of ~200 nM. Treatment with alphaCSPG(scFv)-MAP
      resulted in induction of the mitochondrial stress pathway by activation of
      caspase-9 as well as endonuclease G translocation to the nucleus, while induction
      of the caspase-3 apoptosis pathway was not detectable. Importantly, in vivo
      studies in mice bearing human breast cancer xenografts revealed efficient
      targeting to and accumulation of alphaCSPG4(scFv)-MAP at tumor sites resulting in
      prominent tumor regression. Taken together, this preclinical proof of concept
      study confirms the potential clinical value of alphaCSPG4(scFv)-MAP as a novel
      targeted approach for the elimination of CSPG4-positive TNBC.

PMID- 27037629
TI  - The Molecular Characterization and Immunity Identification of Microneme 3 of
      Eimeria acervulina.
AB  - The gene of Eimeria acervulina microneme protein 3 (EaMIC3) was cloned and
      characterized. According to the conserved sequence, the 3'- and 5'-ends of EaMIC3
      were amplified by the rapid amplification of cDNA ends (RACE). The full length
      cDNA of this gene was obtained by overlapping the sequences of 3'- and 5'
      extremities and amplification by reverse transcription PCR. The sequence analysis
      revealed that the opening reading frame (ORF) of EaMIC3 was 2,607 bp and encoded
      a protein of 868 amino acids with 93.04 kDa. Western blotting assay showed that
      the recombinant protein was successfully recognized by the sera of chickens
      experimentally infected with E. acervulina, whereas the native protein in the
      somatic extract of sporozoites was as well detected by sera from rats immunized
      with the recombinant protein of EaMIC3. Immunofluorescence analysis indicated
      that EaMIC3 was expressed in the sporozoites and merozoites stages of E.
      acervulina. Animal challenge experiments demonstrated that the recombinant
      protein of EaMIC3 could significantly increase the average body weight gains,
      decrease the mean lesion scores and the oocyst outputs of the immunized chickens
      and presented anticoccidial index (ACI) more than 165. Moreover, EaMIC3 protein
      produced significantly high level of IgG antibody, IFN-gamma, IL-10, IL-17 TGF
      beta, CD4+ , and CD8+ .

PMID- 27037630
TI  - Batch-to-batch pharmacokinetic variability confounds current bioequivalence
      regulations: A dry powder inhaler randomized clinical trial.
AB  - Current pharmacokinetic (PK) bioequivalence guidelines do not account for batch
      to-batch variability in study design or analysis. Here we evaluate the magnitude
      of batch-to-batch PK variability for Advair Diskus 100/50. Single doses of
      fluticasone propionate and salmeterol combinations were administered by oral
      inhalation to healthy subjects in a randomized clinical crossover study comparing
      three different batches purchased from the market, with one batch replicated
      across two treatment periods. All pairwise comparisons between different batches
      failed the PK bioequivalence statistical test, demonstrating substantial PK
      differences between batches that were large enough to demonstrate bio
      inequivalence in some cases. In contrast, between-replicate PK bioequivalence was
      demonstrated for the replicated batch. Between-batch variance was ~40-70% of the
      estimated residual error. This large additional source of variability
      necessitates re-evaluation of bioequivalence assessment criteria to yield a
      result that is both generalizable and consistent with the principles of type I
      and type II error rate control. 

PMID- 27037631
TI  - Interpretation of conventional survival analysis and competing-risk analysis: an
      example of hypertension and prostate cancer.

PMID- 27037632
TI  - Delayed dehiscence of the pericarp: role in germination and retention of
      viability of seeds of two cold desert annual Brassicaceae species.
AB  - Considerable variation occurs in post-maturity timing of dehiscence in fruits of
      Brassicaceae species, and several studies have shown that the pericarp plays an
      important role in seed germination and retention of viability in species with
      indehiscent fruits. However, little is known about the significance to seed
      biology of delay in pericarp dehiscence for <1 year in the field. Thus, we
      determined the role of the pericarps of Leptaleum filifolium and Neotorularia
      korolkovii, which open in <1 year after fruit maturity and dispersal, in seed
      germination and retention of seed viability. We compared dormancy-break via after
      ripening in the laboratory and germination phenology and retention of seed
      viability in intact siliques and isolated seeds buried in an experimental garden.
      Seeds of both species have Type 6 non-deep physiological dormancy, which is
      enhanced by the pericarp. Seeds of both species after-ripened during summer 2013,
      and some of them germinated in autumn and some in the following spring in watered
      and non-watered soil. Germination percentages of seeds in siliques increased in
      soil in spring 2014, after the pericarps had opened. Most isolated seeds of L.
      filifolium and N. korolkovii had germinated or were dead by spring 2014 and
      summer 2015, respectively, whereas 60% of the seeds of both species in the
      (opened) pericarps were viable after 24 months. Thus, although the pericarp
      opened 9-10 months after burial, its presence had a significant effect on seed
      dormancy, germination phenology and retention of viability of seeds of L.
      filifolium and N. korolkovii.

PMID- 27037633
TI  - Confirmatory factor analysis of the Alcohol, Smoking and Substance Involvement
      Screening Test (ASSIST) in community health center patients.
AB  - BACKGROUND AND OBJECTIVES: To investigate the factor structure of the Alcohol,
      Smoking, and Substance Involvement Screening Test (ASSIST). METHODS: Secondary
      analysis on an adult primary care sample (N = 2,599). RESULTS AND DISCUSSION:
      Factor analysis of the tobacco, alcohol, and cannabis items did not yield an
      acceptable oblique, three-factor solution, due in part to floor effects and
      limited variability. A short form comprises three items (past-3-month frequency
      of use, urge to use, and whether others have expressed concern for use), that
      showed good psychometrics. SCIENTIFIC SIGNIFICANCE: Supports the need for further
      investigation of the ASSIST factor structure and a short form. (Am J Addict
      2016;25:259-263).

PMID- 27037634
TI  - Protective role of normothermic machine perfusion during reduced-size liver
      transplantation in pigs.
AB  - The purpose of this study is to explore whether normothermic machine perfusion
      (NMP) preservation is superior to cold preservation during reduced-size liver
      transplantation (RSLT) in pigs. Twenty-four healthy Ba-Ma mini pigs were used
      (aged >13 months; weight 25-35 kg; regardless of sex). The animals were
      randomized into 2 groups. In group A (NMP), donor livers were harvested without
      warm ischemia time and heartbeats and then were connected to the NMP system to
      reduce the livers' size under the normothermic condition. In group B (University
      of Wisconsin [UW] solution), donor livers were harvested without warm ischemia
      time and heartbeats after being perfused by UW solution and were then preserved
      in 0 degrees C-4 degrees C UW solution to reduce the livers' size under cold
      conditions. After that, liver transplantation without venovenous bypass was
      performed. General RSLT information of the pigs from the 2 groups was recorded;
      the serological indices were measured; and routine pathological examination of
      liver tissue was observed. A significant difference was observed in the
      intraoperative bleeding between the 2 groups (P < 0.05), whereas no significant
      difference was found in the other indices (all P > 0.05). Significant differences
      of alanine aminotransferase levels, aspartate aminotransferase levels, and
      lactate dehydrogenase levels between the 2 groups were observed between
      postoperative days 3 and 5 (P < 0.05). Significant differences of lactic acid
      levels between the 2 groups were observed between postoperative days 2 and 5 (P <
      0.05). Compared with the cold preservation group, the liver tissues of the NMP
      preservation group only rarely experienced liver cell necrosis and maintained
      integrities in the hepatic sinusoid spaces and endothelial cells. In conclusion,
      NMP preservation is superior to cold preservation during RSLT in pigs. Liver
      Transplantation 22 968-978 2016 AASLD.

PMID- 27037635
TI  - Pediatric Cardiology Fellow Education - Two Important Components.

PMID- 27037636
TI  - ECMO: Incidence and Outcomes of Patients Undergoing the Hybrid Procedure.
AB  - OBJECTIVE: To document the extracorporeal membrane oxygenation (ECMO) incidence
      and outcome in patients undergoing the hybrid procedure at an institution that
      routinely performs this procedure. DESIGN: A retrospective chart review on all
      patients with single ventricle physiology that underwent the hybrid procedure
      between 7/2002 and 12/2014. Patients were excluded if they underwent the hybrid
      procedure after 60 days of birth or subsequently underwent a biventricular
      repair. SETTING: A single center, tertiary pediatric hospital. PATIENTS: One
      hundred eighty-one patients with single ventricle physiology that underwent the
      hybrid procedure between 7/2002 and 12/2014. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: We studied a total of 181 patients (105 males: 76 females).
      Gestational age was 37.8 +/- 2.0 weeks and birth weight was 3.0 +/- 0.7 kg.
      Underlying diagnosis was hypoplastic left heart syndrome in 149 patients and
      other in 32 patients. Age at surgery was 7.8 +/- 6.8 days and weight at surgery
      was 3.1 +/- 0.6 kg. Two patients underwent ECMO support after the hybrid
      procedure. One patient had aortic atresia/mitral atresia and weighed 2.3 kg and
      the other patient had aortic atresia/mitral stenosis and weighed 2.1 kg at time
      of surgery. Both patients died. Incidence of ECMO support after hybrid procedure
      was 1.3% (2/149) for the hypoplastic left heart syndrome patients and 1.1%
      (2/181) for the entire cohort. CONCLUSION: Mortality in patients who underwent
      ECMO after the hybrid procedure was higher than reported for the Norwood
      procedure, however, the incidence of ECMO after hybrid procedure was also
      significantly lower than reported for the Norwood procedure. Future studies are
      needed to determine how to improve outcomes in this complex patient population.

PMID- 27037637
TI  - Melatonin intake since weaning ameliorates steroidogenic function and sperm
      motility of streptozotocin-induced diabetic rats.
AB  - Melatonin may be used as an antioxidant in therapy against systemic sequelae
      caused by oxidative stress in diabetes. However, as melatonin has a major role in
      regulating reproductive activity, its consequence on reproductive parameters
      under diabetes needs to be better clarified. We have studied whether prior and
      concomitant treatment of juvenile Wistar rats with low doses of melatonin
      interferes in reproductive damage induced by experimental diabetes after 1 and 8
      weeks. The consequences of melatonin administration since weaning on reproductive
      parameters of healthy rats at adulthood were also evaluated. Melatonin was
      provided in drinking water (10 MUg/kg b.w./day) after weaning (5-week-old).
      Diabetes was induced by streptozotocin injection (4.5 mg/100 g b.w.) at 13-week
      old rats, and rats were euthanized 1 and 8 weeks after disease onset. Diabetes
      decreased circulating testosterone levels (~35% to 1 week; ~62% to 2 months; p <
      0.01) but did not affect testes sperm counts. Two months of diabetes reduced the
      sperm reserve and led to atrophy of epididymal cauda. Both 1-week and 2-month
      diabetes impaired sperm motility, decreased the number of spermatozoa with
      progressive movement, and increased the number of immotile sperm. Melatonin
      intake reduced serum testosterone levels ~29% in healthy 14-week-old and ~23% in
      21-week-old rats and reduced daily testicular sperm production ~26% in the latter
      disease stage, but did not interfere in sperm reserves and transit time for both
      experimental periods. Exogenous melatonin prevented the serum testosterone
      decrease and damage to sperm motility in diabetic rats and attenuated reduction
      in sperm counts and transit time induced by 1-week diabetes but did not avoid
      this decrease at 2-month diabetes. Low doses of melatonin administered prior to
      and during experimental diabetes attenuated damage to testicular steroidogenic
      activity and preserved sperm motility, but not sperm reserves in the rat. Our
      data indicated a differential action of melatonin in normoglycemic and
      hyperglycemic conditions, particularly in sperm motility and testosterone
      production by Leydig cells.

PMID- 27037638
TI  - Maternal drug or alcohol abuse is associated with decreased head size from mid
      pregnancy to childhood.
AB  - AIM: Maternal alcohol abuse is poorly recognised and causes developmental
      problems. This study explored the foetal central nervous systems (CNS), head
      circumference and psychomotor development of children exposed to drugs or alcohol
      during pregnancy up to 2.5 years of age. METHODS: We recruited 23 pregnant women
      referred to Kuopio University Hospital, Finland, by their family doctor because
      of drug or alcohol abuse, and 22 control mothers. Foetal CNS parameters were
      measured by three-dimensional ultrasonography at the mean gestational age of 20
      weeks and the Griffiths Mental Developmental Scales (GMDS), and anthropometric
      measurements were carried out at the mean ages of one and 2.5 years. RESULTS: The
      exposed foetuses had decreased biparietal and occipito-frontal distances and head
      circumferences, but unchanged cerebellar volume at 20 weeks, and decreased head
      circumferences and length and height at birth, one and 2.5 years of age. They
      scored lower than the controls on the GMDS general quotient and the hearing,
      language and locomotor subscales at 2.5 years of age. CONCLUSION: Maternal
      alcohol or drug exposure was associated with decreased head size from mid
      pregnancy to childhood and reduced development at 2.5 years. Foetal head
      circumference at mid-pregnancy was a useful indicator of substance abuse
      affecting the CNS.

PMID- 27037639
TI  - A systematic review of the effects of novel psychoactive substances 'legal highs'
      on people with severe mental illness.
AB  - WHAT IS KNOWN ON THE SUBJECT?: Novel psychoactive substances (NPS) include
      synthetic drugs mimicking the effects of illicit drugs, e.g. synthetic
      cannabinoids, and herbs such as Salvia divinorum. NPS are substances that can
      trigger hallucinations and other effects altering the mind, and are currently
      uncontrolled by the United Nations' 1961 Narcotic Drugs/1971 Psychotropic
      Substances Conventions. NPS affect brain chemistry that induces the psychoactive
      effects, such as hallucinations and feeling 'high'. It is unknown what effects
      such drugs have on people with severe mental illness (i.e. psychotic illnesses).
      WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Our review demonstrates that little
      is known about the effects of various NPS on people with severe mental illness.
      Almost nothing is known about the long-term consequences of NPS use on the mental
      and physical health of SMI patients. Patients may lack understanding that NPS are
      psychoactive drugs that can impact on their mental and physical wellbeing. WHAT
      ARE THE IMPLICATIONS FOR PRACTICE?: Some patients might be reluctant or do not
      think it is relevant to disclose NPS use. Commonly used illicit drug screening is
      unlikely to detect the presence of NPS, therefore health and mental health
      professionals should directly enquire about NPS and actively encourage patients
      with severe mental illness to disclose any substance use. PATIENT AND PUBLIC
      INVOLVEMENT IN THE RESEARCH: There was no significant patient and public
      involvement in the development and conduct of this study . ABSTRACT: Introduction
      Novel psychoactive substances (NPS) are synthetic substances that have been
      developed to produce altered states of consciousness and perceptions. People with
      severe mental illness (SMI) are more likely to use NPS than people without mental
      illness, but the short- and long-term effects of NPS are largely unknown. Method
      We systematically reviewed the literature about the effects of NPS on people with
      SMI. Results We included 12 case reports, 1 cross-sectional survey and 1
      qualitative study. Participants included mostly males aged between 20 and 35
      years. A variety of NPS were used, including synthetic cathinones and herbs such
      as Salvia. The most commonly reported effects of NPS were psychotic symptoms (in
      some cases novel in form and content to the patients' usual symptoms) and
      significant changes in behaviour, including agitation, aggression and violence.
      Patients' vital signs, such as blood pressure, pulse rate and temperature, were
      also commonly affected. Conclusion NPS potentially have serious effects on people
      with SMI, but our findings have limited generalizability due to a reliance on
      case studies. There is a paucity of evidence about the long-term effects of these
      substances. Further research is required to provide a better understanding about
      how different NPS affect patients' mental and physical health.

PMID- 27037640
TI  - Anal Canal Carcinoma in a Child With Disorders of Sex Development.
AB  - Squamous cell carcinoma of the anal canal in children is rare. To date, the
      etiology and outcome of this condition have been not fully understood. Here, we
      report an 11-year-old child with anal canal cancer who had concomitant disorders
      of sex development. Radiotherapy followed by salvage surgery achieved disease
      free survival of 3 years. Since overexpression of cell cycle regulatory protein
      p16 was immunohistochemically evident in tumor tissue, human papillomavirus
      infection was considered as a causative factor in the carcinogenesis.

PMID- 27037641
TI  - Rationale and design of the ARCUS: Effects of trAnsRadial perCUtaneouS coronary
      intervention on upper extremity function.
AB  - OBJECTIVE: The aim of this study is to provide a complete insight in the access
      site morbidity and upper extremity function after Transradial Percutaneous
      Coronary Intervention (TR-PCI). BACKGROUND: In percutaneous coronary intervention
      the Transradial Approach (TRA) is gaining popularity as a default technique. It
      is a very promising technique with respect to post-procedure complications, but
      the exact effects of TRA on upper extremity function are unknown. METHODS AND
      RESULTS: The effects of trAnsRadial perCUtaneouS coronary intervention on upper
      extremity function (ARCUS) trial is a multicenter prospective cohort study that
      will be conducted in all patients admitted for TR-PCI. Clinical outcomes will be
      monitored during a follow-up of 6 months, with its primary endpoint at two weeks
      of follow-up. To investigate the complete upper extremity function, a combination
      of physical examinations and validated questionnaires will be used to provide
      information on anatomical integrity, strength, range of motion (ROM),
      coordination, sensibility, pain, and functioning in everyday life. Procedural and
      material specifications will be registered in order to include all possible
      aspects influencing upper extremity function. CONCLUSIONS: Results from this
      study will elucidate the effect of TR-PCI on upper extremity function. This
      creates the opportunity to further optimize TR-PCI, to make improvements in
      functional outcome and to prevent morbidity regarding full upper extremity
      function. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037642
TI  - Addendum: hypercaloric diets with high meal frequency, but not increased meal
      size, increase intrahepatic triglycerides: A randomized controlled trial.

PMID- 27037643
TI  - Pelvic floor dysfunction and sensory impairment: Current evidence.
AB  - AIMS: To explore the role of sensory nerve impairment in women with pelvic organ
      prolapse, painful bladder syndrome, urinary and fecal incontinence, and sexual
      dysfunction. METHODS: Medline and Embase were searched for articles in which
      sensory testing, either quantitative sensory testing or current perception
      thresholds, had been used to evaluate women with pelvic organ prolapse, stress
      and urge urinary incontinence, fecal incontinence and female sexual dysfunction.
      All search terms were expanded within each database prior to searching. RESULTS:
      Research to date has included small numbers of participants, used poorly matched
      controls, lacked a systemic sensory examination and applied non-standardized
      sensory testing techniques. However, the evidence suggests women with pelvic
      organ prolapse demonstrate sensory dysfunction. The role of sensory impairment in
      stress urinary incontinence is inconclusive. In women with urge urinary
      incontinence there is some evidence to suggest it may be urethrally mediated.
      Women with painful bladder syndrome may have more sensitive nerve endings which
      are unable to ignore repeated stimuli. Sensory impairment is common in women with
      sexual dysfunction, typically involving larger nerve fibres. There were no
      studies evaluating sensory function in women with fecal incontinence. CONCLUSION:
      Current evidence suggests women with pelvic floor dysfunction demonstrate sensory
      impairment though the causes remain unclear. Further studies are needed to
      investigate the different conditions of pelvic floor dysfunction using
      standardized sensory testing techniques, as well as evaluate the timing and
      mechanism by which any sensory impairment develops. Neurourol. Urodynam. 36:550
      556, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037644
TI  - Liposomal Amphotericin B drug access for the treatment of leishmaniasis in
      Brazil.

PMID- 27037646
TI  - Fine arts curriculum improves observational skills of dermatology trainees: a
      pilot study.

PMID- 27037647
TI  - Molecular epidemiology of selected infectious diseases caused by bacteria in
      juveniles and post-larvae of the white shrimp Penaeus vannamei from the north
      western coast of Mexico.

PMID- 27037645
TI  - Developmental programming: State-of-the-science and future directions-Summary
      from a Pennington Biomedical symposium.
AB  - OBJECTIVE: On December 8-9, 2014, the Pennington Biomedical Research Center
      convened a scientific symposium to review the state-of-the-science and future
      directions for the study of developmental programming of obesity and chronic
      disease. The objectives of the symposium were to discuss: (i) past and current
      scientific advances in animal models, population-based cohort studies, and human
      clinical trials, (ii) the state-of-the-science of epigenetic-based research, and
      (iii) considerations for future studies. RESULTS: This symposium provided a
      comprehensive assessment of the state of the scientific field and identified
      research gaps and opportunities for future research in order to understand the
      mechanisms contributing to the developmental programming of health and disease.
      CONCLUSIONS: Identifying the mechanisms which cause or contribute to
      developmental programming of future generations will be invaluable to the
      scientific and medical community. The ability to intervene during critical
      periods of prenatal and early postnatal life to promote lifelong health is the
      ultimate goal. Considerations for future research including the use of animal
      models, the study design in human cohorts with considerations about the timing of
      the intrauterine exposure, and the resulting tissue-specific epigenetic signature
      were extensively discussed and are presented in this meeting summary.

PMID- 27037648
TI  - Ultrafast Preparation of Black Phosphorus Quantum Dots for Efficient Humidity
      Sensing.
AB  - Black phosphorus quantum dots (BPQDs) have been prepared by a high turbulent
      shear rate generated from a household kitchen blender. A layer-by-layer
      disintegration mechanism of bulk BP crystals is suggested. As-synthesized BPQDs
      have shown excellent humidity sensing and photothermal converting properties.
      Importantly, this work not only explores potential applications for the BPQDs but
      also provides a successful paradigm for preparing the QDs of other layered
      materials.

PMID- 27037649
TI  - What are the causes and outcomes of the coexistence of HBsAg and anti-HBs?

PMID- 27037650
TI  - The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and
      Substantially Prolongs Survival After First Intestinal Transplantation.
AB  - Intestinal transplantation (ITx) remains challenged by frequent/severe rejections
      and immunosuppression-related complications (infections/malignancies/drug
      toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and
      translated it to the clinics. LIP consists of experimentally proven maneuvers,
      destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms:
      donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin
      inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP
      was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational
      cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient
      survival was 92%. One patient died at 9 months due to aspergillosis, another at
      12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early
      acute rejection (AR) developed in two (15%); late AR in three (23%); all were
      reversible. No chronic rejection (CR) occurred. No malignancies developed and
      estimated glomerular filtration rate remained stable post-Tx. At last follow-up
      (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11
      survivors were total parenteral nutrition free with a Karnofsky score >90% in 8
      recipients (follow-up >1 years). A high frequency of circulating CD4+ CD45RA-
      Foxp3hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney
      transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx,
      KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a
      low-inflammatory/pro-regulatory environment activates Tregs at levels similar to
      tolerant-KTx, without causing sensitization. LIP limits rejection under reduced
      IS and thereby prolongs long-term survival to an extent not previously attained
      after ITx.

PMID- 27037651
TI  - Ganciclovir-resistant cytomegalovirus infection in solid organ transplant
      recipients: a single-center retrospective cohort study.
AB  - BACKGROUND: Ganciclovir-resistant cytomegalovirus (GCV-R CMV) is an emerging
      challenge among solid organ transplant (SOT) recipients. The literature suggests
      that about 1% of abdominal transplant recipients develop GCV-R CMV infection. The
      epidemiology and outcome of GCV-R CMV in SOT recipients who have received
      alemtuzumab induction is not well described. METHODS: After Institutional Review
      Board approval, a single-center, retrospective review of 2148 abdominal SOT
      recipients between January 2006 and July 2011 at our institution (n = 2148) was
      conducted to identify patients with proven or empirically treated GCV-R CMV.
      Descriptive statistics on collected demographics, clinical course, and
      therapeutic outcomes were performed. RESULTS: Of 116 SOT recipient treated for
      CMV, 14 patients (12.1% of cases; 0.65% of all SOT patients) had proven or
      suspected GCV-R CMV. Eight (50%) developed GCV-R CMV while receiving
      valganciclovir (valGCV) prophylaxis. The remainder developed late-onset disease,
      after having completed an average 212 days (range 83-353) of prophylaxis.
      Resistance was clinically suspected an average of 103 days (range 10-455) after
      CMV infection was initially identified; 10 patients had confirmed genotypic
      resistance. Foscarnet therapy was associated with resolution of CMV in 13.
      CONCLUSION: Suboptimal dosing of valGCV is associated with development of GCV-R
      CMV. Our observed rate of GCV-R CMV in alemtuzumab-induced patients is similar to
      rates seen to historical data for other induction agents.

PMID- 27037652
TI  - Deoxynivalenol inhibits proliferation and induces apoptosis in human umbilical
      vein endothelial cells.
AB  - Deoxynivalenol (DON) is a stable mycotoxins found in cereals infected by certain
      fungal species and causes adverse health effects in animals and human such as
      vomiting, diarrhea and reproductive toxicity. In this study, we investigated the
      toxic and apoptotic effects of DON in human umbilical vein endothelial cells
      (HUVECs), a good model for studying inflammation. The results show that DON
      significantly inhibited the viability of HUVECs. DON could also inhibit the
      proliferation of HUVECs through G2/M phase arrest in cell cycle progression.
      Moreover, oxidative stress induced by DON was indicated by observations of
      increased levels of reactive oxygen species (ROS). In addition, DON also causes
      mitochondrial damage by decreasing the mitochondrial membrane potential and
      inducing apoptosis by up-regulation of apoptosis-related genes like caspase-3,
      caspase-9, and Bax genes, and down-regulation of Bcl-2 gene. These results
      together suggest that DON could induce cell cycle arrest, oxidative stress, and
      apoptosis in HUVECs. 

PMID- 27037653
TI  - Evaluated the adverse effects of cadmium and aluminum via drinking water to
      kidney disease patients: Application of a novel solid phase microextraction
      method.
AB  - In present study aluminum (Al) and cadmium (Cd) were determined in ground water
      samples and assesses human health risks associated with elevated concentrations
      of toxic metals in dissolved form, using a novel solid phase microextraction
      (SPMUE). Ground water sample (n=200) and biological sample (blood) of patients
      having chronic kidney disorders (CKD) along with healthy control subjects of same
      area (southern part of Pakistan) were collected. A simple system, including the
      micropipette tip packed with modified ionic liquid-activated carbon cloth (IL
      ACC) coated with 8-hydroxyqunilone (8-HQ) attached to syringe. The analytes in
      water and acid digested blood samples were manually drawn for 2-10 cycles
      (drawing/discharging) at different pH range. The analytes sorbed on coated ACC
      were then desorbed with 2.0molL(-1) HNO3 in ethanol by drawing/discharging cycles
      for 1-5 times. The concentration of extracted analytes was determined by
      electrothermal atomic absorption spectrometer. The influence of different
      variables on the extraction efficiency of Cd and Al, were optimized. The Al and
      Cd concentrations in groundwater were found to be elevated than recommended
      limits by the World Health Organization. The urinary N-acetyl-h-glucosaminidase
      values were significantly higher in CKD patients as compared to refrent subjects
      (p<0.001). The significant variation in levels of Cd and Al were observed in
      blood samples of CKD patients than referents subjects (p<0.01). The strong
      positive correlation among Al and Cd levels in groundwater versus blood samples
      of CKD patients (r=0.82-0.85) p<0.01) was observed than those values calculated
      for referent subjects (r=0.425-0.536). 

PMID- 27037654
TI  - Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts
      of Citrus juices in Fe(3+)-induced oxidative stress.
AB  - Exogenous iron in particulate matter and imbalanced iron homeostasis cause
      deleterious effects on health. Natural and synthetic iron chelators may be of
      therapeutic benefit, therefore we evaluated the protective effect of Citrus
      flavonoids-rich extracts from bergamot and orange juices in iron overloaded human
      lung epithelial cells. Cytofluorimetric, biochemical and genotoxic analyses were
      performed in Fe2(SO4)3 exposed A549, pretreated with each extract whose chemical
      composition was previously detected. Chelating activity was assessed in cells by
      a calcein ester. Both extracts reduced the generation of reactive oxygen species
      and membrane lipid peroxidation, improved mitochondrial functionality, and
      prevented DNA-oxidative damage in iron-exposed cells. Antioxidant effects were
      attributed to the chelating property, blocking upstream the redox activity of
      iron. Flavonoid-rich extracts also induced antioxidant catalase. The bergamot and
      orange juice extracts had a broad-spectrum protective effect. Their use prevents
      iron oxidative injury and these natural iron chelators could be used as
      therapeutic agents. 

PMID- 27037655
TI  - Measuring infrastructure: A key step in program evaluation and planning.
AB  - State tobacco prevention and control programs (TCPs) require a fully functioning
      infrastructure to respond effectively to the Surgeon General's call for
      accelerating the national reduction in tobacco use. The literature describes
      common elements of infrastructure; however, a lack of valid and reliable measures
      has made it difficult for program planners to monitor relevant infrastructure
      indicators and address observed deficiencies, or for evaluators to determine the
      association among infrastructure, program efforts, and program outcomes. The
      Component Model of Infrastructure (CMI) is a comprehensive, evidence-based
      framework that facilitates TCP program planning efforts to develop and maintain
      their infrastructure. Measures of CMI components were needed to evaluate the
      model's utility and predictive capability for assessing infrastructure. This
      paper describes the development of CMI measures and results of a pilot test with
      nine state TCP managers. Pilot test findings indicate that the tool has good face
      validity and is clear and easy to follow. The CMI tool yields data that can
      enhance public health efforts in a funding-constrained environment and provides
      insight into program sustainability. Ultimately, the CMI measurement tool could
      facilitate better evaluation and program planning across public health programs.

PMID- 27037658
TI  - Arsenic mobilization from sediments in microcosms under sulfate reduction.
AB  - Arsenic is often assumed to be immobile in sulfidic environments. Here,
      laboratory-scale microcosms were conducted to investigate whether microbial
      sulfate reduction could control dissolved arsenic concentrations sufficiently for
      use in groundwater remediation. Sediments from the Vineland Superfund site and
      the Coeur d'Alene mining district were amended with different combination of
      lactate and sulfate and incubated for 30-40 days. In general, sulfate reduction
      in Vineland sediments resulted in transient and incomplete arsenic removal, or
      arsenic release from sediments. Sulfate reduction in the Coeur d'Alene sediments
      was more effective at removing arsenic from solution than the Vineland sediments,
      probably by arsenic substitution and adsorption within iron sulfides. X-ray
      absorption spectroscopy indicated that the Vineland sediments initially contained
      abundant reactive ferrihydrite, and underwent extensive sulfur cycling during
      incubation. As a result, arsenic in the Vineland sediments could not be
      effectively converted to immobile arsenic-bearing sulfides, but instead a part of
      the arsenic was probably converted to soluble thioarsenates. These results
      suggest that coupling between the iron and sulfur redox cycles must be fully
      understood for in situ arsenic immobilization by sulfate reduction to be
      successful.

PMID- 27037659
TI  - N-nitrosamine formation by monochloramine, free chlorine, and peracetic acid
      disinfection with presence of amine precursors in drinking water system.
AB  - In this study, the formation of eight N-nitrosamines, N-nitrosodimethylamine
      (NDMA), N-nitrosodiethylamine, N-nitrosomethylamine, N-nitrosodi-n-propylamine, N
      nitrosodi-n-butylamine, N-Nitrosopiperidine, N-Nitrosopyrrolidine, N
      Nitrosomorpholine, were systematically evaluated with respect to seven N
      nitrosamine precursors (dimethylamine, trimethylamine, 3
      (dimethylaminomethyl)indole, 4-dimethylaminoantipyrine, ethylmethylamine,
      diethylamine, dipropylamine) and three disinfectants (monochloramine, free
      chlorine, peracetic acid) under variable dosages, exposure times, and pH in a
      drinking water system. Without the presence of the seven selected N-nitrosamine
      precursors N-nitrosamine formation was not observed under any tested condition
      except very low levels of N-Nitrosopyrrolidine under some conditions. With
      selected N-nitrosamine precursors present N-nitrosamines formed at different
      levels under different conditions. The highest N-nitrosamine formation was NDMA
      with a maximum concentration of 1180 ng/L by monochloramine disinfection with
      precursors present; much lower levels of N-nitrosamines were formed by free
      chlorine disinfection; and no detectable level of N-nitrosamines were observed by
      peracetic acid disinfection except low level of N-Nitrosodi-n-propylamine under
      some conditions. NDMA formation was not affected by pH while four other N
      nitrosamine formations were slightly affected by sample pH tested between 7 and
      9, with formation decreasing with increasing pH. Monochloramine exposure time
      study displayed fast formation of N-nitrosamines, largely formed in four hours of
      exposure and maximized after seven days. This was a systematic study on the N
      nitrosamine formation with the seven major N-nitrosamine precursors presence and
      absence under different conditions, including peracetic acid disinfection which
      has not been studied elsewhere.

PMID- 27037660
TI  - Research on metallic iron for environmental remediation: Stopping growing sloppy
      science.
AB  - Research on using metallic iron (Fe(0)) for environmental remediation has boomed
      during the passed two decades. Achieved results have established filtration on
      Fe(0) packed beds as an efficient technology for water treatment at several
      scales. However, the further development of Fe(0)-based filtration systems is
      impaired by useless discussion on the mechanism of contaminant removal. However,
      the whole discussion becomes superfleous while properly considering the
      difference between a chemical and an electrochemical reaction. This note ends the
      discussion and suggests practical ways to avoid the further propagation of the
      mistake.

PMID- 27037661
TI  - Rebound pustular psoriasis after brodalumab discontinuation.

PMID- 27037662
TI  - Field test kits for collection of ignitable liquids and ignitable liquid residues
      used by the NSW fire scene investigators.
AB  - The detection of ignitable liquid residues (ILR) on samples related to fire
      scenes provides investigators with important information. Field test kits were
      developed as an alternative procedure to swabbing using cotton wool and cotton
      tip applicators for situations where direct sampling is not possible. Central to
      the kits is a piece of white absorbent non-woven material consisting of
      polypropylene fibres (cloth). Experiments were carried out in our laboratory
      using the polypropylene cloths and cotton wool for collection of burnt and
      unburnt petrol residues from porous and non-porous surfaces. Every aspect of this
      new procedure was validated, involving more than 200 analyses of fire debris
      samples, where the polypropylene cloth was used to sample ILR comprising all
      common accelerants. The use of field test kits for collection of petrol and
      medium petroleum distillate (MPD) residues from hands was validated on the hands
      of 11 volunteers. The polypropylene cloth was found to be suitable for
      application in field test kits for the collection and recovery of petroleum-based
      liquids and liquid residues from both fire scenes and hands. 

PMID- 27037663
TI  - A thermoanalytical, X-ray diffraction and petrographic approach to the forensic
      assessment of fire affected concrete in the United Arab Emirates.
AB  - For most fires, forensic investigation takes place well after building materials
      have cooled and knowledge of the structural damage due to heat exposure can
      reveal the temperature reached during an incident. Recently, there have been
      significant changes in the types and hence characteristics of cementitious
      materials used in the United Arab Emirates. Few studies focus on the application
      of thermo-analytical, X-ray diffraction and petrographic techniques on newly
      developed structures and this work aims to address this deficiency by utilising a
      series of parametric laboratory-based tests to assess the effects of heat on
      hardened concrete. Specimens were made with a design mix typically used for low
      rise residential homes and storage facilities. The key constituents were:
      Portland cement (PC), crushed gabbro stone and dune sand with water/cement ratios
      of 0.4-0.5. Portland cement substitutes included ground granulated blast-furnace
      slag (GGBS), and silica fume (SF) at replacement percentages of up to 50% and 4%,
      respectively. The concrete cubes of 100-mm size were produced and standard cured
      to 28 days and then exposed to heat inside an electric furnace with pre
      determined temperature regimes of 150 degrees C, 300 degrees C, 600 degrees C and
      900 degrees C. Petrographic examination was utilised to compare the
      discolouration of the cooled concrete. Data derived from thermogravimetric
      analysis (TGA) and differential scanning calorimetry (DSC) are reported in order
      to assess the usefulness of these techniques in fire scene investigation to
      differentiate between these temperature regimes. The results from the TGA
      indicate that the majority of the percentage weight loss for all the mixtures
      occurred in the range 650-700 degrees C, which corresponds to the decarbonation
      of calcium carbonate, mainly from the aggregates. The endothermic DSC peak at 70
      120 degrees C relates to the loss of evaporable water. Since both of these
      reactions are irreversible, this information can help fire investigators estimate
      the temperature history of concrete after exposure to fire. On the other hand,
      the portlandite in the cement matrix dehydroxylates at 450-550 degrees C but then
      reforms as the concrete cools. The onset temperature for the dehydroxylation of
      the reformed mineral is always lower than in virgin samples and its enthalpy
      furthermore depends strongly on the thermal history of the portlandite. Thus,
      this feature can be used to establish the temperature to which the material was
      exposed to during a fire incident.

PMID- 27037664
TI  - Localized aggressive periodontitis immune response to healthy and diseased
      subgingival plaque.
AB  - AIM: The objective of this case-control study was to compare the inflammatory
      response of peripheral blood from localized aggressive periodontitis (LAP)
      patients when stimulated with healthy or diseased plaque samples. MATERIALS AND
      METHODS: Whole blood and subgingival plaque samples were collected from 13 LAP
      subjects, 14 siblings of LAP subjects and six periodontally healthy individuals.
      Whole blood was stimulated for 24 h with plaque samples generated from healthy or
      diseased sites. The levels of 14 cyto/chemokines were detected using multiplex
      technology. RESULTS: Localized aggressive periodontitis-derived cultures
      displayed higher levels of G-CSF, INFgamma, IL10, IL12p40, IL1beta, IL-6, IL-8,
      MCP-1, MIP-1alpha, and TNFalpha, than control cultures regardless of stimulus
      used. Whole blood from healthy siblings displayed higher levels of IL-6 compared
      to control subjects, but lower levels than those observed in cultures from LAP
      participants. CONCLUSIONS: This study suggests that although bacteria is an
      important factor in eliciting the hyper-inflammatory response observed in LAP
      patients, the predisposition of host's response to bacterial presence may play a
      more significant role than the components of the stimulatory plaque.

PMID- 27037665
TI  - The interrelationship between attentional and executive deficits in major
      depressive disorder.
AB  - OBJECTIVE: Cognitive dysfunction is an established feature of major depressive
      disorder (MDD). However, it remains unclear whether deficits in different
      cognitive domains are relatively independent or originate from a circumscribed
      'primary deficit'. This study tested the hypothesis that a deficit in attention
      represents a primary deficit in depression. METHOD: Neuropsychological function
      was assessed in 30 depressed patients with MDD and 34 control participants.
      Cognitive composites were derived from a minimum of three tests and included
      attention, executive function, visuospatial memory and verbal memory. A
      multivariate analysis of variance was used to assess group differences in overall
      cognitive performance, and multiple regression models were used to evaluate the
      role of attention in deficits in other domains. RESULTS: The cognitive deficit in
      the depressed sample was found to be characterized by poorer performance in
      attention and executive function. When evaluating the interrelationship between
      the two deficits, the attentional deficit was found to persist when variability
      in executive function was statistically accounted for, whilst the executive
      deficit was eliminated when attention was accounted for. CONCLUSION: The results
      demonstrated that the attentional deficit could not be explained by deficits in
      executive function, which provides support for a primary attention deficit in
      depression.

PMID- 27037666
TI  - Respiratory Science.

PMID- 27037667
TI  - Recent advances on the functional and evolutionary morphology of the amniote
      respiratory apparatus.
AB  - Increased organismic complexity in metazoans was achieved via the specialization
      of certain parts of the body involved in different faculties (structure-function
      complexes). One of the most basic metabolic demands of animals in general is a
      sufficient supply of all tissues with oxygen. Specialized structures for gas
      exchange (and transport) consequently evolved many times and in great variety
      among bilaterians. This review focuses on some of the latest advancements that
      morphological research has added to our understanding of how the respiratory
      apparatus of the primarily terrestrial vertebrates (amniotes) works and how it
      evolved. Two main components of the respiratory apparatus, the lungs as the
      "exchanger" and the ventilatory apparatus as the "active pump," are the focus of
      this paper. Specific questions related to the exchanger concern the structure of
      the lungs of the first amniotes and the efficiency of structurally simple snake
      lungs in health and disease, as well as secondary functions of the lungs in heat
      exchange during the evolution of sauropod dinosaurs. With regard to the active
      pump, I discuss how the unique ventilatory mechanism of turtles evolved and how
      understanding the avian ventilatory strategy affects animal welfare issues in the
      poultry industry. 

PMID- 27037668
TI  - Inhibition of Leptin-ObR Interaction Does not Prevent Leptin Translocation Across
      a Human Blood-Brain Barrier Model.
AB  - The adipocyte-derived hormone leptin regulates appetite and energy homeostasis
      through the activation of leptin receptors (ObR) on hypothalamic neurones; hence,
      leptin must be transported through the blood-brain barrier (BBB) to reach its
      target sites in the central nervous system. During obesity, however, leptin BBB
      transport is decreased, in part precluding leptin as a viable clinical therapy
      against obesity. Although the short isoform of the ObR (ObRa) has been implicated
      in the transport of leptin across the BBB as a result of its elevated expression
      in cerebral microvessels, accumulating evidence indicates that leptin BBB
      transport is independent of ObRa. In the present study, we employed an ObR
      neutralising antibody (9F8) to directly examine the involvement of endothelial
      ObR in leptin transport across an in vitro human BBB model composed of the human
      endothelial cell line hCMEC/D3. Our results indicate that, although leptin
      transport across the endothelial monolayer was nonparacellular, and energy- and
      endocytosis-dependent, it was not inhibited by pre-treatment with 9F8, despite
      the ability of the latter to recognise hCMEC/D3-expressed ObR, prevent leptin-ObR
      binding and inhibit leptin-induced signal transducer and activator of
      transcription 3 (STAT-3) phosphorylation in hCMEC/D3 cells. Furthermore, hCMEC/D3
      cells expressed the transporter protein low-density lipoprotein receptor-related
      protein-2 (LRP-2), which is capable of binding and endocytosing leptin. In
      conclusion, our results demonstrate that leptin binding to and signalling through
      ObR is not required for efficient transport across human endothelial monolayers,
      indicating that ObR is not the primary leptin transporter at the human BBB, a
      role which may fall upon LRP-2. A deeper understanding of leptin BBB transport
      will help clarify the exact causes for leptin resistance seen in obesity and aid
      in the development of more efficient BBB-penetrating leptin analogues.

PMID- 27037669
TI  - A comparison of preference-assessment methods.
AB  - In Study 1, we evaluated preference stability across 4 preference-assessment
      methods for 6 individuals, 5 of whom had autism spectrum disorder and 1 of whom
      had traumatic brain injury. We also measured participants' problem behavior as a
      corollary measure during all assessment methods. The highest mean correlation
      coefficients and Kendall rank coefficients of concordance across administrations
      were observed for the paired-stimulus and multiple-stimulus-without-replacement
      methods. Lower correspondence across administrations was observed for the free
      operant and response-restriction methods. Although differentially higher levels
      of problem behavior did not occur with a single method, lower levels were
      consistently observed with the free-operant method. During Study 2, we evaluated
      the implications of lower coefficients on reinforcer efficacy by comparing an
      initially identified and an immediately identified high-preference stimulus in a
      reinforcer assessment. Initially identified and immediately identified high
      preference stimuli were equally effective reinforcers, suggesting that
      fluctuations in preference do not necessarily affect reinforcer efficacy in
      practice.

PMID- 27037670
TI  - Role of riboswitches in gene regulation and their potential for algal
      biotechnology.
AB  - Riboswitches are regulatory elements in messenger RNA to which specific ligands
      can bind directly in the absence of proteins. Ligand binding alters the mRNA
      secondary structure, thereby affecting expression of the encoded protein.
      Riboswitches are widespread in prokaryotes, with over 20 different effector
      ligands known, including amino acids, cofactors, and Mg(2+) ions, and gene
      expression is generally regulated by affecting translation or termination of
      transcription. In plants, fungi, and microalgae, riboswitches have been found,
      but only those that bind thiamine pyrophosphate. These eukaryotic riboswitches
      operate by causing alternative splicing of the transcript. Here, we review the
      current status of riboswitch research with specific emphasis on microalgae. We
      discuss new riboswitch discoveries and insights into the underlying mechanism of
      action, and how next generation sequencing technology provides the motivation and
      opportunity to improve our understanding of these rare but important regulatory
      elements. We also highlight the potential of microalgal riboswitches as a tool
      for synthetic biology and industrial biotechnology.

PMID- 27037671
TI  - Clustering of metabolic risk factors and adverse pregnancy outcomes: a
      prospective cohort study.
AB  - BACKGROUND: The relative contributions of a cluster of metabolic risk factors to
      pregnancy complications are not fully understood. We investigated the correlation
      between clustering of metabolic risk factors and adverse pregnancy outcomes.
      METHODS: This prospective cohort study was performed on pregnant women who sought
      health care during their whole gestation in a women's and children's hospital.
      The pregnancy outcomes were also followed. Pre-pregnancy overweight/obesity, as
      well as pregnancy high triglycerides, low high-density lipoprotein-cholesterol,
      hyperglycemia and raised blood pressure were defined as metabolic risk factors.
      Adverse pregnancy outcomes included preterm delivery, small/large for gestational
      age, preeclampsia, gestational diabetes mellitus, neonatal asphyxia and foetal
      demise. Stratified analyses were conducted on a total of 5535 women according to
      classification in each metabolic risk factor. The adjusted odds ratio (OR) for
      adverse pregnancy outcomes according to the number of clustering metabolic
      factors was calculated using the logistic regression analysis. RESULTS: The
      number of metabolic risk factors and adverse pregnancy outcomes were positively
      correlated (Ptrend  < 0.001). Compared with women without a metabolic risk
      factor, women with one metabolic risk factor had a risk (OR = 1.67 95%CI 1.42
      1.96) of adverse pregnancy outcomes. Women with a cluster of two metabolic risk
      factors tended to develop more adverse pregnancy outcomes (OR = 3.32 95% CI 2.69
      4.10), and the risk was much higher in women with a cluster of three or more
      metabolic risk factors (OR = 10.40 95%CI 7.37-14.69). CONCLUSIONS: Pregnant women
      with a cluster of metabolic risk factors are more likely to have adverse
      pregnancy outcomes. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037672
TI  - Enantioselective Synthesis of Silacyclopentanes.
AB  - A variety of functionalized silacyclopentanes were synthesized by highly
      enantioselective beta-eliminations of silacyclopentene oxides followed by
      stereospecific transformations. The reaction mechanism of the beta-elimination
      was elucidated by DFT calculations. An in vitro biological assay with an oxy
      functionalized silacyclopentane showed substantial binding to a serotonin
      receptor protein.

PMID- 27037673
TI  - Invited review: Microtubule severing enzymes couple atpase activity with tubulin
      GTPase spring loading.
AB  - Microtubules are amazing filaments made of GTPase enzymes that store energy used
      for their own self-destruction to cause a stochastically driven dynamics called
      dynamic instability. Dynamic instability can be reproduced in vitro with purified
      tubulin, but the dynamics do not mimic that observed in cells. This is because
      stabilizers and destabilizers act to alter microtubule dynamics. One interesting
      and understudied class of destabilizers consists of the microtubule-severing
      enzymes from the ATPases Associated with various cellular Activities (AAA+)
      family of ATP-enzymes. Here we review current knowledge about GTP-driven
      microtubule dynamics and how that couples to ATP-driven destabilization by
      severing enzymes. We present a list of challenges regarding the mechanism of
      severing, which require development of experimental and modeling approaches to
      shed light as to how severing enzymes can act to regulate microtubule dynamics in
      cells. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 547-556, 2016. 

PMID- 27037675
TI  - The importance of including imperfect detection models in eDNA experimental
      design.
AB  - Environmental DNA (eDNA) is DNA that has been isolated from field samples, and it
      is increasingly used to infer the presence or absence of particular species in an
      ecosystem. However, the combination of sampling procedures and subsequent
      molecular amplification of eDNA can lead to spurious results. As such, it is
      imperative that eDNA studies include a statistical framework for interpreting
      eDNA presence/absence data. We reviewed published literature for studies that
      utilized eDNA where the species density was known and compared the probability of
      detecting the focal species to the sampling and analysis protocols. Although
      biomass of the target species and the volume per sample did not impact
      detectability, the number of field replicates and number of samples from each
      replicate were positively related to detection. Additionally, increased number of
      PCR replicates and increased primer specificity significantly increased
      detectability. Accordingly, we advocate for increased use of occupancy modelling
      as a method to incorporate effects of sampling effort and PCR sensitivity in eDNA
      study design. Based on simulation results and the hierarchical nature of
      occupancy models, we suggest that field replicates, as opposed to molecular
      replicates, result in better detection probabilities of target species. 

PMID- 27037674
TI  - Epilepsy diagnostic and treatment needs identified with a collaborative database
      involving tertiary centers in France.
AB  - OBJECTIVE: To obtain perspective on epilepsy in patients referred to tertiary
      centers in France, and describe etiology, epilepsy syndromes, and identify
      factors of drug resistance and comorbidities. METHODS: We performed a cross
      sectional analysis of the characteristics of 5,794 pediatric and adult patients
      with epilepsy included in a collaborative database in France between 2007 and
      2013. Comparisons between groups used Student's t-test or Fisher's exact test for
      binary or categorical variables. Factors associated with drug resistance and
      intellectual disability were evaluated in multi-adjusted logistic regression
      models. RESULTS: Mean age at inclusion was 17.9 years; children accounted for
      67%. Epilepsy was unclassified in 20% of patients, and etiology was unknown in
      65%, including those with idiopathic epilepsies. Etiologies differed
      significantly in adult- when compared to pediatric-onset epilepsy; however, among
      focal structural epilepsies, mesial temporal lobe epilepsy with hippocampal
      sclerosis began as often in the pediatric as in adult age range. Drug resistance
      concerned 53% of 4,210 patients evaluable for seizure control and was highest in
      progressive myoclonic epilepsy (89%), metabolic diseases (84%), focal cortical
      dysplasia (70%), other cortical malformations (69%), and mesial temporal lobe
      epilepsy with hippocampal sclerosis (67%). Fifty-nine percent of patients with
      focal structural epilepsy and 69% with epileptic encephalopathies were drug
      resistant; however, 40-50% of patients with West syndrome and epileptic
      encephalopathy with continuous spike-and-waves during sleep were seizure-free.
      Ages at onset in infancy and in young adults shared the highest risk of drug
      resistance. Epilepsy onset in infancy comprised the highest risk of intellectual
      disability, whereas specific cognitive impairment affected 36% of children with
      idiopathic focal epilepsy. SIGNIFICANCE: Our study provides a snapshot on
      epilepsy in patients referred to tertiary centers and discloses needs for
      diagnosis and treatment. Large databases help identify patients with rare
      conditions that could benefit from specific prospective studies.

PMID- 27037676
TI  - Factorial validity and measurement invariance of the Perceived Susceptibility to
      Sport Injury scale.
AB  - The Perceived Susceptibility to Sport Injury (PSSI) scale is a measure that has
      recently surfaced in the sport injury literature. The factor structure of the
      PSSI scale has not been subjected to a rigorous factor analysis; thus, the
      factorial validity of the measure in athlete populations is unknown. To establish
      the validity of the PSSI scale in sports medicine research, the purpose of this
      study was to examine the factor structure and measurement invariance across
      gender of the PSSI scale. Male and female intercollegiate athletes (N = 217)
      completed the PSSI scale during the off-season. The factor structure was analyzed
      using confirmatory factor analysis (CFA) procedures and maximum likelihood
      estimation. The measurement invariance analysis was conducted via comparisons of
      fit indices within a series of hierarchically constrained models. Results of the
      CFA yielded a very good fit of the measurement model: chi2 (2) = 4.535, P =
      0.104; RMSEA = 0.076; SRMR = 0.018; CFI = 0.995; NNFI = 0.985. Results of the
      measurement invariance analysis demonstrated strict invariance across gender, and
      no significant latent mean differences emerged between men and women. Study
      results support the factorial validity of the PSSI scale for use in future sports
      medicine research.

PMID- 27037677
TI  - Antihypertensive Properties of a Pea Protein Hydrolysate during Short- and Long
      Term Oral Administration to Spontaneously Hypertensive Rats.
AB  - This study investigated short-term (24 h) and long-term (5 wk) systolic blood
      pressure (SBP)-lowering effects in spontaneously hypertensive rats (SHR) of a 5
      kDa membrane pea protein hydrolysate permeate (PPH-5) produced through thermoase
      hydrolysis of pea protein isolate (PPI). Amino acid analysis showed that the PPH
      5 had lower contents of sulfur-containing amino acids than the PPI. Size
      exclusion chromatography indicated mainly low molecular weight (<10 kDa) peptides
      in PPH-5 but not in the PPI. The PPH-5 had renin and angiotensin converting
      enzyme inhibition IC50 values of 0.57 and 0.10 mg/mL (P < 0.05), respectively,
      and consisted mainly of peptides with 2 to 6 amino acids. Mass spectrometry
      analysis revealed mainly hydrophilic tetrapeptide sequences. After a single oral
      administration (100 mg/kg body weight) to SHR, the unheated PPI showed weakest (P
      < 0.05) SBP-lowering effect with a -4 mm Hg maximum when compared to -25 mm Hg
      for heat-treated PPI and -36 mm Hg for PPH-5. Incorporation of the PPH-5 as 0.5%
      or 1% (w/w) casein substitute in the SHR diet produced maximum SBP reductions of 
      22 or -26 mm Hg (P < 0.05), respectively after 3 wk. In comparison, the
      unhydrolyzed PPI produced a maximum SBP reduction of -17 mm Hg also after 3 wk.
      Potency of the pea products decreased in the 4th and 5th wk, though SBP values of
      the treated rats were still lower than the untreated control. We conclude that
      the antihypertensive potency of PPH-5 may have been due to the presence of easily
      absorbed hydrophilic peptides. 

PMID- 27037678
TI  - Reliability Analysis of Lithium Disilicate Crowns: Effectof Veneering and Milling
      Production Workflow.

PMID- 27037679
TI  - Quantitative determination of regorafenib and its two major metabolites in human
      plasma with high-performance liquid chromatography and ultraviolet detection.
AB  - A simple, highly sensitive and specific high-performance liquid chromatography
      (HPLC) method was developed for the simultaneous quantitation of regorafenib, N
      oxidemetabolite (M-2) and the desmethyl N-oxide metabolite (M-5) in human plasma.
      Regorafenib, M-2, M-5 and the internal standard sorafenib were separated using a
      mobile phase of 0.5% KH2 PO4 (pH 3.5)-acetonitrile (30:70, v/v), on a Capcell PAK
      MG II column at a flow rate of 0.5 mL/min and measurement at UV 260 nm. The lower
      limits of quantification for regorafenib, M-2 and M-5 were 10 ng/mL for each
      analyte. A procedure using solid-phase extraction required only a small amount of
      plasma (100 MUL) for one analysis while providing high extraction recovery (>81%
      for all compounds) and good selectivity. Coefficients of variation for intra- and
      inter-day assays were <12.2% for regorafenib, <12.3% for M-2 and <15.1% for M-5.
      Accuracies for intra- and inter-day assays were <9.4% for regorafenib, <8.0% for
      M-2 and <12.8% for M-5 over a linear range from 10 to 10,000 ng/mL. This HPLC
      assay is suitable for clinical pharmacokinetic studies of regorafenib. The
      present HPLC method is currently in use for our observational studies of patients
      under treatment. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27037680
TI  - Estimation of time-shift models with application to survival calibration in
      health technology assessment.
AB  - The incremental life expectancy, defined as the difference in mean survival times
      between two treatment groups, is a crucial quantity of interest in cost
      effectiveness analyses. Usually, this quantity is very difficult to estimate from
      censored survival data with a limited follow-up period. The paper develops
      estimation procedures for a time-shift survival model that, provided model
      assumptions are met, gives a reliable estimate of incremental life expectancy
      without extrapolation beyond the study period. Methods for inference are
      developed both for individual patient data and when only published Kaplan-Meier
      curves are available. Through simulation, the estimators are shown to be close to
      unbiased and constructed confidence intervals are shown to have close to nominal
      coverage for small to moderate sample sizes. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27037681
TI  - Escape from the cryptic species trap: lichen evolution on both sides of a
      cyanobacterial acquisition event.
AB  - Large, architecturally complex lichen symbioses arose only a few times in
      evolution, increasing thallus size by orders of magnitude over those from which
      they evolved. The innovations that enabled symbiotic assemblages to acquire and
      maintain large sizes are unknown. We mapped morphometric data against an eight
      locus fungal phylogeny across one of the best-sampled thallus size transition
      events, the origins of the Placopsis lichen symbiosis, and used a phylogenetic
      comparative framework to explore the role of nitrogen-fixing cyanobacteria in
      size differences. Thallus thickness increased by >150% and fruiting body core
      volume increased ninefold on average after acquisition of cyanobacteria. Volume
      of cyanobacteria-containing structures (cephalodia), once acquired, correlates
      with thallus thickness in both phylogenetic generalized least squares and
      phylogenetic generalized linear mixed-effects analyses. Our results suggest that
      the availability of nitrogen is an important factor in the formation of large
      thalli. Cyanobacterial symbiosis appears to have enabled lichens to overcome size
      constraints in oligotrophic environments such as acidic, rain-washed rock
      surfaces. In the case of the Placopsis fungal symbiont, this has led to an
      adaptive radiation of more than 60 recognized species from related crustose
      members of the genus Trapelia. Our data suggest that precyanobacterial symbiotic
      lineages were constrained to forming a narrow range of phenotypes, so-called
      cryptic species, leading systematists until now to recognize only six of the 13
      species clusters we identified in Trapelia.

PMID- 27037682
TI  - Lentivirus-mediated somatic recombination and development of a novel mouse model
      for sporadic colorectal cancer.
AB  - In this study, we have developed a novel mouse model for sporadic colorectal
      cancer (CRC) by utilizing APC conditional knockout (Apc(CKO) ) mouse and
      lentivirus encoding Cre recombinase and a reporter gene (EGFP or LacZ).
      Lentiviral transduction of colonic crypt stem cells allowed for the long-term
      expression of reporter gene as well as excision of floxed Apc alleles, which
      resulted in tumor development. Tumors represented adenoma stages along with the
      nuclear accumulation of beta-catenin. Loss of E-cadherin at the cellular
      junctions and strong expression of Vimentin suggested the sign of active
      epithelial-mesenchymal transition. Moreover, nuclear staining of Ki67 inside
      epithelial cells of aberrant crypts demonstrated their higher proliferative
      nature. Erratic downstream signaling of activated Wnt/beta-catenin, AKT/mTOR, and
      Notch pathways provided strong evidence towards the higher proliferative index of
      epithelial cells inside the aberrant crypts. These results do recapitulate the
      findings of previous APC mutant mouse models. Our model represents sporadic CRC
      more precisely as (i) tumors result from somatic mutations but not from germline;
      (ii) tumors develop in colon not in small intestine; (iii) few tumors develop at
      the distal end of colons. Additionally, our model allows for the long-term
      expression of the gene(s), which get integrated into the host cell genome and
      provides an ability to track the tumor growth. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037683
TI  - Long-term human primary hepatocyte cultures in a microfluidic liver biochip show
      maintenance of mRNA levels and higher drug metabolism compared with Petri
      cultures.
AB  - Human primary hepatocytes were cultivated in a microfluidic bioreactor and in
      Petri dishes for 13 days. mRNA kinetics in biochips showed an increase in the
      levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6, HNF4a, SULT1A1, UGT1A1
      mRNA related genes when compared with post extraction levels. In addition,
      comparison with Petri dishes showed higher levels of CYP2B6, CYP2C19, CYP2C8,
      CYP3A4, CYP1A2, CYP2D6 related genes at the end of culture. Functional assays
      illustrated a higher urea and albumin production over the period of culture in
      biochips. Bioreactor drug metabolism (midazolam and phenacetin) was not superior
      to the Petri dish after 2 days of culture. The CYP3A4 midazolam metabolism was
      maintained in biochips after 13 days of culture, whereas it was almost
      undetectable in Petri dishes. This led to a 5000-fold higher value of the
      metabolic ratio in the biochips. CYP1A2 phenacetin metabolism was found to be
      higher in biochips after 5, 9 and 13 days of culture. Thus, a 100-fold higher
      metabolic ratio of APAP in biochips was measured after 13 days of perfusion.
      These results demonstrated functional primary human hepatocyte culture in the
      bioreactor in a long-term culture. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27037684
TI  - Involvement of an ethylene response factor in chlorophyll degradation during
      citrus fruit degreening.
AB  - Chlorophyll degradation naturally occurs during plant senescence. However, in
      fruit such as citrus, it is a positive characteristic, as degreening is an
      important colour development contributing to fruit quality. In the present work,
      Citrus sinensis Osbeck, cv. Newhall fruit was used as a model for chlorophyll
      degradation. An ethylene response factor, CitERF13, was isolated and its
      transcriptional changes were closely correlated with fruit peel degreening during
      development or in response to ethylene. Dual-luciferase and yeast one-hybrid
      assays, as well as motif mutation, indicated that CitERF13 directly binds to the
      CitPPH promoter and enhances its activity. Transient and stable over-expression
      of CitERF13 resulted in rapid chlorophyll degradation in Nicotiana tabacum leaves
      and led to accumulation of pheophorbide (Pheide) a, a metabolite of pheophorbide
      hydrolase (PPH). Similar results were observed from transient transformation of
      CitERF13 in citrus fruit peel. Moreover, this function of CitERF13 was conserved
      within Arabidopsis and tomato, as the homologs AtERF17 and SlERF16 similarly
      acted as activators of PPH genes and accelerators of chlorophyll degradation.

PMID- 27037685
TI  - Evaluation of an Assistive Telepresence Robot for Elderly Healthcare.
AB  - In this paper we described the telepresence robot system designed to improve the
      well-being of elderly by supporting them to do daily activities independently, to
      facilitate social interaction in order to overcome a sense of social isolation
      and loneliness as well as to support the professional caregivers in everyday
      care. In order to investigate the acceptance of the developed robot system,
      evaluation study involved elderly people and professional caregivers, as two
      potential user groups was conducted. The results of this study are also presented
      and discussed. 

PMID- 27037686
TI  - Performance Evaluation of Color Models in the Fusion of Functional and Anatomical
      Images.
AB  - Fusion of the functional image with an anatomical image provides additional
      diagnostic information. It is widely used in diagnosis, treatment planning, and
      follow-up of oncology. Functional image is a low-resolution pseudo color image
      representing the uptake of radioactive tracer that gives the important metabolic
      information. Whereas, anatomical image is a high-resolution gray scale image that
      gives structural details. Fused image should consist of all the anatomical
      details without any changes in the functional content. This is achieved through
      fusion in de-correlated color model and the choice of color model has greater
      impact on the fusion outcome. In the present work, suitability of different color
      models for functional and anatomical image fusion is studied. After converting
      the functional image into de-correlated color model, the achromatic component of
      functional image is fused with an anatomical image by using proposed
      nonsubsampled shearlet transform (NSST) based image fusion algorithm to get new
      achromatic component with all the anatomical details. This new achromatic and
      original chromatic channels of functional image are converted to RGB format to
      get fused functional and anatomical image. Fusion is performed in different color
      models. Different cases of SPECT-MRI images are used for this color model study.
      Based on visual and quantitative analysis of fused images, the best color model
      for the stated purpose is determined. 

PMID- 27037687
TI  - A Multi-Constraint Scheme with Authorized Mechanism for the Patient Safety.
AB  - Many research works have attempted to introduce passive RFID technology into
      medical systems to reduce medical errors. However, most of these proposed works
      focused on identifying patients and objects. If an RFID based medical system is
      only good for identifying patients and medical objects but not capable of halting
      any medical process immediately, then it is not possible to prevent medical
      errors from happening. Our research focuses on a mechanism to detect and to avoid
      medical harm before it occurs to patients. In this paper, we propose to
      incorporate multiple-constraints into the authorization scheme and used this
      scheme as a basis for implementing a medical management system avoiding medical
      errors to assist medical staff. Specifically, our scheme ensures that a medical
      operation is if and only if enabled when the constraints are being satisfied that
      an "identified patient" is being treated by a "certified medical staff member"
      within an "authorized area". In practical environments, our authorization scheme
      can be applied to various healthcare applications, and we develop a prototype
      system and test it in three applications: X-ray control, specimen collection, and
      blood transfusion management. The experimental results show that the system can
      be used to enable X-ray when the X-ray is in authorized location and operated by
      authorized operator. For the specimen collection and blood transfusion, the logs
      showing which medical staff has done specimen or blood transfusion on which
      patient at authorized location are correctly recorded into Hospital Information
      System (HIS). The locating process can be performed within 10 to 20 seconds, and
      the locating error is less than 2 meters. 

PMID- 27037688
TI  - Predictors and clinical consequences of starting androgen therapy in men with low
      testosterone: results from the SIAMO-NOI registry.
AB  - PURPOSE: Management of late onset hypogonadism (LOH) is not homogenous. The aim
      of the study is to observe the management of patients with low testosterone (T)
      in highly specialized Italian centres. METHODS: The SIAMO-NOI is an observational
      longitudinal disease registry for the evaluation of the clinical management of
      patients with low T levels (total T < 12 nmol/L, calculated free T < 225 pmol/l
      or already in treatment) in 15 Italian centers members of the Italian Society for
      Andrology and Sexual Medicine (SIAMS). Clinical and biochemical data were
      collected for four visits during 12 months of observation. RESULTS: 432 patients
      (mean age 50.9 +/- 14.9 years) were enrolled. Of them, 247 men were receiving
      androgen therapy, whereas 145 were naive. After the first visit (V0), 80 men
      started androgen therapy, whereas 55 remained untreated during the entire
      observation. Younger age [odds ratio (OR) 0.57 (0.35-0.92)], total T < 8 nmol/l
      [OR 4.69 (1.59-13.81)], complaining at least one sexual symptom [OR 11.55 (2.01
      66.35)] and reporting more severe lower urinary tract symptoms [OR 1.27 (1.01
      1.60)] predicted starting an androgen therapy. Sixty-four men started therapy
      immediately after V0 and maintained it until the observation end. When compared
      to V0, they reported an increase in all the domains of the International Index of
      Erectile Function-15 (IIEF-15), in the sexual and physical subdomains of the
      Aging Male Scale as well as in the International Prostate Symptom Score.
      Conversely, the untreated group reported a significant improvement, although
      lower than the treated group, only in the erectile function domain of the IIEF
      15. CONCLUSIONS: Management of LOH in SIAMS centres is in line with the
      international guidelines and the newest knowledge about the role of T on prostate
      health. Androgen therapy is associated with an improvement in all the aspects of
      sexual life and in the perception of physical strength.

PMID- 27037690
TI  - Genetic and Neuroimaging Features of Personality Disorders: State of the Art.
AB  - Personality disorders often act as a common denominator for many psychiatric
      problems, and studies on personality disorders contribute to the etiopathology,
      diagnosis, and treatment of many mental disorders. In recent years, increasing
      evidence from various studies has shown distinctive features of personality
      disorders, and that from genetic and neuroimaging studies has been especially
      valuable. Genetic studies primarily target the genes encoding neurotransmitters
      and enzymes in the serotoninergic and dopaminergic systems, and neuroimaging
      studies mainly focus on the frontal and temporal lobes as well as the limbic
      paralimbic system in patients with personality disorders. Although some studies
      have suffered due to unclear diagnoses of personality disorders and some have
      included few patients for a given personality disorder, great opportunities
      remain for investigators to launch new ideas and technologies in the field. 

PMID- 27037692
TI  - A fusion protein consisting of the exopeptidases PepN and PepX-production,
      characterization, and application.
AB  - Nowadays, general and specific aminopeptidases are of great interest, especially
      for protein hydrolysis in the food industry. As shown previously, it is confirmed
      that the general aminopeptidase N (PepN; EC 3.4.11.2) and the proline-specific
      peptidase PepX (EC 3.4.14.11) from Lactobacillus helveticus ATCC 12046 show a
      synergistic effect during protein hydrolysis which results in high degrees of
      hydrolysis and reduced bitterness. To combine both activities, the enzymes were
      linked and a fusion protein called PepN-L1-PepX (FUS-PepN-PepX) was created.
      After production and purification, the fusion protein was characterized. Some of
      its biochemical characteristics were altered in favor for an application compared
      to the single enzymes. As an example, the optimum temperature for the PepN
      activity increased from 30  degrees C for the single enzyme to 35  degrees C for
      FUS-PepN. In addition, the temperature stability of PepX was higher for FUS-PepX
      than for the single enzyme (50 % compared to 40 % residual activity at 50 
      degrees C after 14 days, respectively). In addition, the disulfide bridge
      reducing reagent beta-mercaptoethanol did not longer inactivate the FUS-PepN
      activity. Furthermore, the K M values decreased for both enzyme activities in the
      fusion protein. Finally, it was found that the synergistic hydrolysis performance
      in a casein hydrolysis was not reduced for the fusion protein. The increase of
      the relative degree of hydrolysis of a prehydrolyzed casein solution was the same
      as it was for the single enzymes. As a benefit, the resulting hydrolysate showed
      a strong antioxidative capacity (ABTS-IC50 value: 5.81 MUg mL(-1)). 

PMID- 27037691
TI  - Non-coding RNAs as Emerging Regulators of Neural Injury Responses and
      Regeneration.
AB  - Non-coding RNAs (ncRNAs) are a large cluster of RNAs that do not encode proteins,
      but have multiple functions in diverse cellular processes. Mounting evidence
      indicates the involvement of ncRNAs in the physiology and pathophysiology of the
      central and peripheral nervous systems. It has been shown that numerous ncRNAs,
      especially microRNAs and long non-coding RNAs, are differentially expressed after
      insults such as acquired brain injury, spinal cord injury, and peripheral nerve
      injury. These ncRNAs affect neuronal survival, neurite regrowth, and glial
      phenotype primarily by targeting specific mRNAs, resulting in translation
      repression or degradation of the mRNAs. An increasing number of studies have
      investigated the regulatory roles of microRNAs and long non-coding RNAs in neural
      injury and regeneration, and thus a new research field is emerging. In this
      review, we highlight current progress in the field in an attempt to provide
      further insight into post-transcriptional changes occurring after neural injury,
      and to facilitate the potential use of ncRNAs for improving neural regeneration.
      We also suggest potential directions for future studies. 

PMID- 27037693
TI  - Mixed consortia in bioprocesses: role of microbial interactions.
AB  - The utilization of mixed consortia or mixed culture has become a current research
      trend of applied microbiology, bioprocess engineering and biotechnology. The
      constituent microorganisms of such mixed cultures can jointly perform complex
      processes efficiently, yielding the desired product at an augmented rate, in
      comparison to monocultures. It is understandable that the interactions between
      the microbial partners in these mixed cultures are expected to have a significant
      impact on the combined performance of the microorganisms and the bioprocess as a
      whole. Prevalence of positive interactions (commensalism or mutualism) among
      microbial members of a mixed culture or consortia can significantly enhance the
      product outcome of the bioprocess, ensuring their industrial application and long
      term stability. On the contrary, negative interaction (parasitism, predation or
      ammensalism) leads to elimination of microbial members from the consortia causing
      the destruction of community structure as well as disruption of cumulative
      performance. Therefore, a priori knowledge on the type of interaction between the
      microorganisms is also essential for the optimization of the performance of the
      designed consortia. This could only be achieved through the study of inter
      microbial interaction prevailing in a mixed culture. In the present article,
      different bioprocess applications of mixed cultures, currently in practice along
      with types of positive microbial interactions involved, have been reviewed.
      Complexity of mixed cultures from the perspective of multiple types of intra
      culture relationships has been explained in detail. Overall, the necessity for
      more in-depth research studies on "microbial interaction" in mixed culture
      bioprocesses has been stressed in the article. 

PMID- 27037694
TI  - Co-culture-inducible bacteriocin production in lactic acid bacteria.
AB  - It is common knowledge that microorganisms have capabilities, like the production
      of antimicrobial compounds, which do not normally appear in ideal laboratory
      conditions. Common antimicrobial discovery techniques require the isolation of
      monocultures and their individual screening against target microorganisms. One
      strategy to achieve expression of otherwise hidden antimicrobials is induction by
      co-cultures. In the area of bacteriocin-producing lactic acid bacteria, there has
      been some research focusing into the characteristics of co-culture-inducible
      bacteriocin production and particularly the molecular mechanism(s) of such
      interactions. No clear relationship has been seen between bacteriocin-inducing
      and bacteriocin-producing microorganisms. The three-component regulatory system
      seems to be playing a central role in the induction, but inducing compounds have
      not been identified or characterized. However, the presence of the universal
      messenger molecule autoinducer-2 has been associated in some cases with the co
      culture-inducible bacteriocin phenotype and it may play the role in the
      additional regulation of the three-component regulatory system. Understanding the
      mechanisms of induction would facilitate the development of strategies for
      screening and development of co-culture bacteriocin-producing systems and novel
      products as well as the perseverance of such systems in food and down to the
      intestinal tract, possibly conferring a probiotic effect on the host. 

PMID- 27037695
TI  - Assessment of physicochemical parameters and prevalence of virulent and multiple
      antibiotic-resistant Escherichia coli in treated effluent of two wastewater
      treatment plants and receiving aquatic milieu in Durban, South Africa.
AB  - The poor operational status of some wastewater treatment plants often result in
      the discharge of inadequately treated effluent into receiving surface waters.
      This is of significant public health concern as there are many informal
      settlement dwellers (ISDs) that rely on these surface waters for their domestic
      use. This study investigated the treatment efficiency of two independent
      wastewater treatment plants (WWTPs) in Durban, South Africa and determined the
      impact of treated effluent discharge on the physicochemical and microbial quality
      of the receiving water bodies over a 6-month period. Presumptive Escherichia coli
      isolates were identified using biochemical tests and detection of the mdh gene
      via PCR. Six major virulence genes namely eae, hly, fliC, stx1, stx2, and rfbE
      were also detected via PCR while antibiotic resistance profiles of the isolates
      were determined using Kirby-Bauer disc diffusion assay. The physicochemical
      parameters of the wastewater samples ranged variously between 9 and 313.33 mg/L,
      1.52 and 76.43 NTUs, and 6.30 and 7.87 for COD, turbidity, and pH respectively,
      while the E. coli counts ranged between 0 and 31.2 * 10(3) CFU/ml. Of the 200
      selected E. coli isolates, the hly gene was found in 28 %, fliC in 20 %, stx2 in
      17 %, eae in 14 %, with stx1 and rfbE in only 4 % of the isolates. Notable
      resistance was observed toward trimethoprim (97 %), tetracycline (56 %), and
      ampicillin (52.5 %). These results further highlight the poor operational status
      of these WWTPs and outline the need for improved water quality monitoring and
      enforcement of stringent guidelines.

PMID- 27037696
TI  - Heavy metals contamination and human health risk assessment around Obuasi gold
      mine in Ghana.
AB  - Gold mining has increased the prevalence and occurrence of heavy metals
      contamination at the Earth's surface and is causing major concern due to the
      potential risk involved. This study investigated the impact of gold mine on heavy
      metals (As, Cd, Cr, Cu, Pb, Hg, Ni, Fe, Mn, and Zn) pollution and evaluated the
      potential health risks to local residents via consumption of polluted
      groundwater, agricultural soils, and vegetable crops grown at three community
      farms surrounding the mine at Obuasi municipality of Ghana. The results showed
      levels of As, Cd, Cr, Hg, Fe, and Mn higher than the allowable drinking water
      standards. The vegetable samples analyzed showed high accumulation of As and Ni
      above the normal value. Bioaccumulation factors of heavy metals were
      significantly higher for vegetables grown in the Sanso soils. Estimated average
      daily intake and hazard quotient for As in drinking water as well as As, Pb, and
      Hg in vegetable samples exceeded permissible limit. Unacceptable non-cancer
      health risk levels were found in vegetable samples analyzed for As, Pb, and Hg.
      An unacceptable cancer risk was found via drinking of groundwater, in consumption
      of vegetables, and in soil. The hazard index for vegetables was higher than 1,
      indicating very high health risk to heavy metals contamination through
      consumption of vegetables grown around the sampling sites. The results recommend
      the need for regular monitoring of groundwater and food crops to protect
      consumers' health. 

PMID- 27037697
TI  - Impact of the Pb and Zn ore mining industry on the pollution of the Biala
      Przemsza River, Poland.
AB  - The development of mining and metallurgic industries of Pb and Zn ores in the
      Biala Przemsza catchment area has had a strong influence on the condition of the
      surface water and bottom sediments. In the following study, total contents of
      metals and metalloids were researched in the water and bottom sediment samples
      from the Biala Przemsza River. The samples were collected monthly in 2014 at five
      sampling points along the river. The research helped to determine correlations
      between the parameters and components of the water environment
      (metals/metalloids, cations/anions, pH, Eh, conductivity, carbon (TOC, IC, TC),
      and suspension). The contents of metals and metalloids were determined with
      inductively coupled plasma-mass spectrometry (ICP-MS), whereas anions and cations
      were investigated with ion chromatography (IC). The simplified Community Bureau
      of Reference (BCR) three-step sequential chemical extraction was performed on
      Biala Przemsza River bottom sediments collected in April, July, and October. At
      its lower course, the Biala Przemsza River water did not meet the Polish surface
      water quality standards. The Biala Przemsza River water is mainly loaded with
      metals. Toxic concentrations of Cd, Pb, and Zn were observed at sampling points
      in Okradzionow and Slawkow. The toxic Tl concentration was exceeded (2-6 MUg/L)
      at three sampling points. The Biala Przemsza River bottom sediments were composed
      mostly of medium and fine sand. The BCR extraction of the bottom sediments
      demonstrated that Cd and Zn were bound to cations/anions and carbonates loosely
      adsorbed on the bottom sediments in spring and summer. Such a situation was
      observed at all the sampling points, except for BP3 in Okradzionow. The organic
      carbon concentration increased along the river course.

PMID- 27037698
TI  - Water Quality Index (WQI) of Jaguari and Atibaia Rivers in the region of
      Paulinia, Sao Paulo, Brazil.
AB  - Due to the concern with the quality of hydric resources, the monitoring is
      essential to evaluate and identify the anthropogenic and environmental
      interferences in a quantitative and qualitative level. In order to assist the
      interpretation of the water status of hydric bodies, the gathering of analytical
      data often considers the Water Quality Index (WQI). This index transforms
      technical information in description of the water quality status, highlighting
      the effectiveness of its use and guiding the decision-making process when
      necessary. The aim of this research is to assess the water quality of a region in
      Sao Paulo State, Brazil, by means of the WQI of Jaguari and Atibaia Rivers. The
      period of intense drought, which affected the Brazilian southeast in 2014, was
      evaluated and compared to the mean values recorded from October 2009 to March
      2015, correlating the values of Escherichia coli and the biochemical oxygen
      demand (BOD). One hundred nine samples were collected, being 53 from dry seasons,
      between October and March, and 56 from rainy seasons, between April and
      September. The WQIs in Jaguari and Atibaia Rivers, during dry season, were of
      42.2 (medium) and 36.7 (bad), respectively. The same pattern was registered for
      the dry season, for both rivers, with indices values of 40.1 for Jaguari River
      (medium) and 34.9 for Atibaia River (bad). This research presented the need of an
      effective evaluation of the environmental quality and preservation by competent
      organs for both rivers. Due to the detected conditions, special attention should
      be given to the Atibaia River. 

PMID- 27037700
TI  - An Incredible Mentor: a Tribute to Dick Bakemeier.

PMID- 27037699
TI  - Development of Plain Language Supplemental Materials for the Biobank Informed
      Consent Process.
AB  - The US Department of Health and Human Services addresses clear communication in
      the informed consent process as part of the Notice of Proposed Rulemaking for
      revisions to the Common Rule. However, prior research has shown that participants
      may not fully comprehend research studies despite completion of an informed
      consent process. Our main goal was to provide plain language information about
      donation processes to a cancer biobank to supplement an informed consent form. We
      developed and conducted cognitive testing with supplemental brochures that
      clearly communicated information about three different models for consent
      (notice, broad and study-specific) to future use of biospecimens. During the
      brochure development process, we conducted qualitative, semi-structured,
      individual, in-person cognitive interviews among 14 women to examine
      participants' perceptions of the brochures. Each participant provided feedback
      regarding the understandability, graphics and layout, and cultural
      appropriateness of the brochures. Our findings demonstrate that these methods may
      be used to tailor consent form brochures, such as the ones developed here, to
      other populations. This study therefore adds to our understanding of how best to
      present content to help women from two different racial groups make informed
      decisions about participation in a cancer biobank.

PMID- 27037701
TI  - Barriers to Implementing Person-Centered Recovery Planning in Public Mental
      Health Organizations in Texas: Results from Nine Focus Groups.
AB  - Despite being an established practice in the disabilities service systems, person
      centered planning is a relatively new practice in the behavioral health system.
      As a result, little is known about the barriers that mental health organizations
      face in implementing person-centered recovery planning (PCRP). To fill this gap,
      results are presented from a qualitative analysis of nine focus groups at three
      public mental health organizations in Texas that have been implementing PCRP for
      at least 2 years. Findings suggest that organizations experienced 12 distinct
      barriers to PCRP implementation which were categorized into the Consolidated
      Framework for Implementation Research domains of intervention characteristics,
      the outer setting, the inner setting, characteristics of individuals, and the
      implementation process. Half of these 12 barriers fell within the inner setting
      domain, suggesting that implementation efforts should be flexible and adaptable
      to organizational culture and context. One-quarter of the barriers fell into the
      domain of characteristics of individuals involved in the intervention, which
      further suggests implementation efforts should assess the impact that both staff
      and consumers have on implementation success.

PMID- 27037702
TI  - Safety of outpatient laparoscopic cholecystectomy in children: analysis of 2050
      elective ACS NSQIP-pediatric cases.
AB  - PURPOSE: Limited data exists evaluating the extent of utilization and safety of
      outpatient laparoscopic cholecystectomy (LC) in children. The aim of this study
      was to investigate the safety of outpatient LC in the pediatric population
      utilizing a national surgical quality improvement database. METHODS: The National
      Surgical Quality Improvement Program-Pediatric (NSQIP-P) databases from 2012 and
      2013 were queried to identify pediatric patients who underwent elective LC.
      Patients who underwent outpatient LC were compared with those who underwent
      inpatient LC. Outcomes of interest included 30-day overall morbidity,
      readmission, and reoperation. RESULTS: A total of 2,050 LC were identified, 995
      (48.5 %) were performed as an outpatient procedure and 1055 (51.5 %) as
      inpatient. Patients who underwent outpatient LC were more often white (79.6 vs.
      69.2 %; p = <0.0001). Choledocholithiasis was more often treated in inpatient
      setting (12.5 vs. 1.7 %; p < 0.0001), while biliary dyskinesia was performed in
      outpatient setting (26.1 v. 12.6 %; p = 0.0001). Overall 30-day morbidity was
      greater in the inpatient group (2.5 vs. 0.8 %; p = 0.03). There were no
      differences in term of 30-day readmission rate and related reoperations (0.9 vs
      0.3 % respectively; p = 0.09). CONCLUSION: This analysis of a large multicenter
      dataset demonstrates that pediatric patients without significant associated
      comorbidities can safely undergo laparoscopic cholecystectomy as an outpatient
      procedure.

PMID- 27037703
TI  - The involvement of TRP channels in sensory irritation: a mechanistic approach
      toward a better understanding of the biological effects of local irritants.
AB  - Peripheral nerves innervating the mucosae of the nose, mouth, and throat protect
      the organism against chemical hazards. Upon their stimulation, characteristic
      perceptions (e.g., stinging and burning) and various reflexes are triggered
      (e.g., sneezing and cough). The potency of a chemical to cause sensory irritation
      can be estimated by a mouse bioassay assessing the concentration-dependent
      decrease in the respiratory rate (50 % decrease: RD50). The involvement of the N.
      trigeminus and its sensory neurons in the irritant-induced decrease in
      respiratory rates are not well understood to date. In calcium imaging
      experiments, we tested which of eight different irritants (RD50 5-730 ppm) could
      induce responses in primary mouse trigeminal ganglion neurons. The tested
      irritants acetophenone, 2-ethylhexanol, hexyl isocyanate, isophorone, and
      trimethylcyclohexanol stimulated responses in trigeminal neurons. Most of these
      responses depended on functional TRPA1 or TRPV1 channels. For crotyl alcohol, 3
      methyl-1-butanol, and sodium metabisulfite, no activation could be observed. 2
      ethylhexanol can activate both TRPA1 and TRPV1, and at low contractions (100 uM)
      G protein-coupled receptors (GPCRs) seem to be involved. GPCRs might also be
      involved in the mediation of the responses to trimethylcyclohexanol. By using
      neurobiological tools, we showed that sensory irritation in vivo could be based
      on the direct activation of TRP channels but also on yet unknown interactions
      with GPCRs present in trigeminal neurons. Our results showed that the potency
      suggested by the RD50 values was not reflected by direct nerve-compound
      interaction. 

PMID- 27037704
TI  - Neutrophil apoptosis is delayed in an equine model of colitis: Implications for
      the development of systemic inflammatory response syndrome.
AB  - BACKGROUND: Horses that develop colitis invariably exhibit signs of a systemic
      inflammatory response syndrome (SIRS). A significant contributor to the
      development of SIRS in human subjects is delayed neutrophil apoptosis, but this
      has not been specifically studied in horses. OBJECTIVES: To determine the
      occurrence of ex vivo neutrophil apoptosis and its contribution to the
      development of SIRS in an equine colitis model. STUDY DESIGN: Experiment using a
      colitis model. METHODS: Neutrophils were isolated before and after the induction
      of colitis using an oligofructose overdose model, placed into culture for 12 h or
      24 h with or without lipopolysaccharide (LPS) at various concentrations, and
      assessed for the occurrence of apoptosis using Annexin V and propidium iodide
      staining with flow cytometric quantification. Levels of caspase-3, -8 and -9
      activity were measured after 12 h of incubation in neutrophil lysates. RESULTS:
      Ex vivo neutrophil apoptosis was significantly delayed in neutrophils isolated
      after the induction of colitis (12-h incubation: P = 0.004; 24-h incubation: P =
      0.003) with concomitant reductions in caspase-3, -8 and -9 activity (caspase-3: P
      = 0.004; caspase-8: P = 0.02; caspase-9: P = 0.02). Neutrophils isolated after
      the induction of colitis were refractory to LPS-delayed apoptosis. Neutrophil
      apoptosis was delayed with increasing cell concentration in vitro. MAIN
      LIMITATIONS: The main limitation of the study is the that the exact mechanism for
      delayed neutrophil apoptosis following the induction of colitis was not fully
      elucidated. CONCLUSIONS: The data show that neutrophil apoptosis is delayed in
      horses following the induction of colitis as a result of interference with the
      intrinsic and extrinsic apoptotic pathways, which may contribute to the
      development of equine SIRS. Concurrent development of neutrophilia may contribute
      to a prolonged neutrophil lifespan through a concentration-dependent delay in
      apoptosis.

PMID- 27037705
TI  - Immune Priming, Fat Reserves, Muscle Mass and Body Weight of the House Cricket is
      Affected by Diet Composition.
AB  - Some insect species are capable of producing an enhanced immune response after a
      first pathogenic encounter, a process called immune priming. However, whether and
      how such ability is driven by particular diet components (protein/carbohydrate)
      have not been explored. Such questions are sound given that, in general, immune
      response is dietary dependent. We have used adults of the house cricket Acheta
      domesticus L. (Orthoptera: Gryllidae) and exposed them to the bacteria Serratia
      marcescens. We first addressed whether survival rate after priming and nonpriming
      treatments is dietary dependent based on access/no access to proteins and
      carbohydrates. Second, we investigated how these dietary components affected fat
      reserves, muscle mass, and body weight, three key traits in insect fitness. Thus,
      we exposed adult house crickets to either a protein or a carbohydrate diet and
      measured the three traits. After being provided with protein, primed animals
      survived longer compared to the other diet treatments. Interestingly, this effect
      was also sex dependent with primed males having a higher survival than primed
      females when protein was supplemented. For the second experiment, protein-fed
      animals had more fat, muscle mass, and body weight than carbohydrate-fed animals.
      Although we are not aware of the immune component underlying immune priming, our
      results suggest that its energetic demand for its functioning and/or consequent
      survival requires a higher demand of protein with respect to carbohydrate. Thus,
      protein shortage can impair key survival-related traits related to immune and
      energetic condition. Further studies varying nutrient ratios should verify our
      results. 

PMID- 27037706
TI  - Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists Utilizing
      Data from the Exenatide Clinical Trial Development Program.
AB  - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated benefits
      for patients with type 2 diabetes including A1C reduction and weight loss with
      minimal risk of hypoglycemia. This article provides an evidence-based update of
      safety and tolerability considerations for the clinical use of GLP-1RAs as a
      class, with a specific detailed review of data from the exenatide clinical trial
      development program, which has the longest history and availability of safety and
      tolerability data as the first-approved GLP-1RA. Specific areas covered include
      comparative risk of hypoglycemia, as well as pancreatic, thyroid, and
      cardiovascular safety data; clinical guidance regarding current safety and
      tolerability data is also reviewed. 

PMID- 27037707
TI  - The impact of ADHD on the health and well-being of ADHD children and their
      siblings.
AB  - Childhood attention-deficit/hyperactivity disorder (ADHD) has been associated
      with reduced health and well-being of patients and their families. The authors
      undertook a large UK survey-based observational study of the burden associated
      with childhood ADHD. The impact of ADHD on both the patient (N = 476) and their
      siblings (N = 337) on health-related quality of life (HRQoL) and happiness was
      quantified using multiple standard measures [e.g. child health utility-9D (CHU
      9D), EuroQol-5D-Youth]. In the analysis, careful statistical adjustments were
      made to ensure a like-for-like comparison of ADHD families with two different
      control groups. We controlled for carers' ADHD symptoms, their employment and
      relationship status and siblings' ADHD symptoms. ADHD was associated with a
      significant deficit in the patient's HRQoL (with a CHU-9D score of around 6 %
      lower). Children with ADHD also have less sleep and were less happy with their
      family and their lives overall. No consistent decrement to the HRQoL of the
      siblings was identified across the models, except that related to their own
      conduct problems. The siblings do, however, report lower happiness with life
      overall and with their family, even when controlling for the siblings own ADHD
      symptoms. We also find evidence of elevated bullying between siblings in families
      with a child with ADHD. Overall, the current results suggest that the reduction
      in quality of life caused by ADHD is experienced both by the child with ADHD and
      their siblings.

PMID- 27037708
TI  - Phenotypic and chemotypic studies using Arabidopsis and yeast reveal that GHB
      converts to SSA and induce toxicity.
AB  - gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound. It is detected
      in organisms such as yeasts, plants and mammals. GHB is produced from the
      reduction of succinic semialdehyde (SSA) by the activity of GHB dehydrogenase.
      Arabidopsis genome contains two GHB dehydrogenase encoding genes. The
      accumulation of GHB in ssadh mutants led to the speculation that GHB is the cause
      of aberrant phenotypes. Conversely, the accumulation of GHB in Arabidopsis plants
      subjected to abiotic stresses was described as a way of avoiding SSA induced
      damage. To resolve these contrasting views on GHB, we examined the effect of
      exogenous GHB and SSA on the growth of yeast and Arabidopsis plants. GHB
      concentrations up to 1.5 mM didn't affect shoots of Arabidopsis plants; however,
      root growth was inhibited. In contrast, 0.3 mM SSA has severely affected the
      growth of plants. Treatment of yeast wild-type strain with 10 mM SSA and 10 mM
      GHB didn't affect the growth. However, the growth of yeast uga2 mutant was
      greatly inhibited by the same concentration of SSA, but not GHB. Metabolic
      analysis and enzyme activity assay on native gel showed that Arabidopsis, but not
      yeast, possesses a GHB dehydrogenase activity that converts GHB back to SSA. The
      enzymatic assay has also indicated the existence of an additional GHB
      dehydrogenase encoding gene(s) in Arabidopsis genome. Taken together, we conclude
      that GHB is less toxic than SSA. Its accumulation in ssadh mutants and during
      abiotic stresses is a response to avoid the SSA induced damage. 

PMID- 27037709
TI  - Tailored therapy for different presentations of chronic pain after stapled
      hemorrhoidopexy.
AB  - BACKGROUND: As stapled hemorrhoidopexy (SH) becomes more widely used, we see more
      patients with chronic postoperative anal pain after this surgery. Its
      presentation is variable and difficult to treat. The aim of our study was to
      investigate the impact of chronic anal pain after SH and whether tailored therapy
      was likely to achieve a favorable outcome. METHODS: We retrospectively analyzed
      31 consecutive patients with chronic anal pain who had undergone SH in other
      hospitals and were referred to our institutions. Depending on the type of pain,
      unrelated (at rest) or related to defecation, two groups of patients were
      identified. Moreover, the mean distance of the staple line from the anal verge
      was calculated in both groups. Treatments included: topical nifedipine, local
      anesthetic and steroid infiltration, removal of retained staples, anal dilation,
      and scar excision with mucosal suturing. A visual analog scale (VAS) was used to
      compare pain at baseline, postoperatively, and in the follow-up. This mean
      difference of the VAS score between stages was always used as the main outcome
      measure, depending on the type of presentation, type of pain, and type of
      treatment. Treatment response was defined as a 50 % decrease of VAS from
      baseline. RESULTS: There were 22 males and 9 females. The overall median age was
      43 years (range 21-62 years). On digital examination and proctoscopy, 15 (48 %)
      patients had inflammatory changes, 19 (61 %) patients had staple retention, 8 (26
      %) patients had anorectal stenosis, and 30 (97 %) patients had scar tissue. All
      patients had one or more of the following treatments listed from the least to
      most invasive: topical nifedipine in 12 (39 %) patients, anal dilation in 6 (19
      %) patients, anesthetic and steroid infiltration in 18 (58 %) patients, removal
      of staples in 10 (32 %) patients, and scar excision in 18 (58 %) patients. The
      mean VAS score at baseline was 6.100, +/- 1.953 SD, which dropped significantly
      after treatment to 1.733, +/- 1.658 SD (p < 0.001) and remained low at follow-up
      (1.741 +/- SD 1.251; p < 0.743). In patients with pain at rest (n = 20, 65 %),
      the symptoms improved in 19 (95 %) patients, while the VAS score decreased from
      5.552 +/- 2.115 SD to 1.457 +/- 1.440 SD (95 % CI 3.217-4.964; p < 0.001). In
      patients with post-evacuation pain (n = 11, 35 %), the symptoms improved in 11
      (100 %) patients, while the VAS score decreased from 6.429 +/- 1.835 SD to 1.891
      +/- 1.792 SD (95 % CI 3.784-5.269; p < 0.001). Rating of response based on
      presentation was 90.0 % (0.9/10) after treatment of staple retention, which led
      to a significant decrease in the mean VAS score from 6.304 +/- 1.845 SD to 1.782
      +/- 1.731 SD (95 % CI 3.859-5.185; p < 0.001). Anal stenosis was successfully
      treated in 100.0 % (n = 8/8) of cases with the mean VAS score dropping from 6.500
      +/- 1.309 SD to 2.125 +/- 1.808 SD (95 % CI 2.831-5.919; p < 0.001). Anal
      inflammation improved in 60.0 % (n = 9/15) of patients and the mean VAS score
      dropped from 6.006 +/- 2.138 SD to 1.542 +/- 1.457 SD (95 % CI 3.217-4.964; p <
      0.001). The response after scar tissue treatment was 94 % (n = 17/18) of patients
      with a mean VAS decreasing from 6.117 +/- 2.006 SD to 1.712 +/- 1.697 SD (95 % CI
      3.812-4.974; p < 0.001). Success for topical nifedipine was between 13 and 25 %
      of patients depending on the clinical presentation. Anal dilation was successful
      in 75 % of patients, while Anesthetic and steroid infiltration in 23-54 % of
      patients depending on the clinical presentation. Staple removal was successful in
      77 % of patients, and scar excision with mucosal suturing in 94 % of patients.
      CONCLUSIONS: Our retrospective study suggests that most patients with chronic
      anal pain after SH may be cured with treatment by applying a stepwise approach
      from the least to the most invasive treatment.

PMID- 27037710
TI  - Comments to: surgical management of pelvic organ prolapse in women.

PMID- 27037711
TI  - Key Considerations and Methods in the Study of Gene-Environment Interactions.
AB  - With increased involvement of genetic data in most epidemiological
      investigations, gene-environment (G * E) interactions now stand as a topic, which
      must be meticulously assessed and thoroughly understood. The level, mode, and
      outcomes of interactions between environmental factors and genetic traits have
      the capacity to modulate disease risk. These must, therefore, be carefully
      evaluated as they have the potential to offer novel insights on the "missing
      heritability problem", reaching beyond our current limitations. First, we review
      a definition of G * E interactions. We then explore how concepts such as the
      early manifestation of the genetic components of a disease, the heterogeneity of
      complex traits, the clear definition of epidemiological strata, and the effect of
      varying physiological conditions can affect our capacity to detect (or miss) G *
      E interactions. Lastly, we discuss the shortfalls of regression models to study G
      * E interactions and how other methods such as the ReliefF algorithm, pattern
      recognition methods, or the LASSO (Least Absolute Shrinkage and Selection
      Operator) method can enable us to more adequately model G * E interactions.
      Overall, we present the elements to consider and a path to follow when studying
      genetic determinants of disease in order to uncover potential G * E interactions.

PMID- 27037713
TI  - Attenuated Heart Rate Recovery After Exercise Testing and Risk of Incident
      Hypertension in Men.
AB  - BACKGROUND: Although attenuated heart rate recovery (HRR) and reduced heart rate
      (HR) reserve to maximal exercise testing are associated with adverse
      cardiovascular outcomes, their relation to incident hypertension in healthy
      normotensive populations is unclear. We examined the hypothesis that both
      attenuated HRR and reduced HR reserve to exercise testing are associated with
      incident hypertension in men. METHODS: A total of 1,855 participants were
      selected comprising of healthy, initially normotensive men who underwent peak or
      symptom-limited treadmill testing at baseline. HRR was calculated as the
      difference between peak HR during exercise testing and the HR at 2 minutes after
      exercise cessation. HR reserve was calculated as the percentage of HR reserve
      (peak HR - resting HR)/(220 - age - resting HR) * 100. RESULTS: During an average
      4-year follow-up, 179 (9.6%) men developed hypertension. Incident hypertension
      was associated with HRR quartiles (Q1 (<42 (bpm)) 12.5%, Q2 (43-49 bpm) 8.5%, Q3
      (50-56 bpm) 9.3%, and Q4 (>57 bpm) 8.3%; P = 0.05 for trend). The relative risk
      (RR) of the incident hypertension in the slowest HRR quartile vs. the fastest HRR
      quartile was 1.78 (95% confidence interval (CI): 1.14-2.78) after adjustment for
      confounders. Every 1 bpm increment in HRR was associated with a 2% (RR 0.98, 95%
      CI: 0.97-0.99) lower risk of incident hypertension after adjusting for potential
      confounders. In contrast, reduced HR reserve did not predict the risk of incident
      hypertension. CONCLUSIONS: Slow HRR after exercise testing is independently
      associated with the development of hypertension in healthy normotensive men.

PMID- 27037712
TI  - Orthostatic Circulatory Disorders: From Nosology to Nuts and Bolts.
AB  - When patients complain of altered consciousness or discomfort in the upright
      posture, either relieved by recumbency or culminating in syncope, physicians may
      find themselves baffled. There is a wide variety of disorders that cause abnormal
      regulation of blood pressure and pulse rate in the upright posture. The aim of
      this focused review is 3-fold. First, to offer a classification (nosology) of
      these disorders; second, to illuminate the mechanisms that underlie them; and
      third, to assist the physician in the practical aspects of diagnosis of adult
      orthostatic hypotension, by extending clinical skills with readily available
      office technology.

PMID- 27037714
TI  - State policy environment and the dental safety net: a case study of professional
      practice environments' effect on dental service availability in Federally
      Qualified Health Centers.
AB  - OBJECTIVES: To determine whether and to what extent the state policy environment
      for the dental hygiene workforce affects the availability of dental services at
      Federally Qualified Health Centers (FQHCs). METHODS: We examined data drawn from
      the Uniform Data System on 1,135 unique FQHC grantees receiving community health
      center funding from the U.S. Health Center program between 2004 and 2012. The
      Dental Hygiene Professional Practice Index was used to quantify variations in
      state policy environment. We then examined the influence of state policy
      environment on the availability of dental care through generalized linear mixed
      effects models. RESULTS: Approximately 80% of FQHCs reported delivering dental
      services. We consistently observed that FQHCs with favorable levels of state
      support had the highest proportion of FQHCs that delivered dental services, even
      more so than FQHCs with extremely high support. FQHCs located in the most
      restrictive states had 0.28 the odds of delivering dental services as did those
      located in the most supportive states. CONCLUSIONS: The state policy environment
      for the dental hygiene workforce is likely associated with the availability of
      dental services at FQHCs. The greatest proportion of FQHCs delivering dental
      services was found in states with policy provisions supporting professional
      independence in public health settings. Nevertheless, additional research is
      needed to understand the specific mechanism by which these policies affect FQHCs.

PMID- 27037715
TI  - Quantitative analysis of the reconstruction errors of the currently popular
      algorithm of magnetic resonance electrical property tomography at the interfaces
      of adjacent tissues.
AB  - This work quantitatively analyzed the reconstruction errors (REs) of electrical
      property (EP) images using a currently popular algorithm of magnetic resonance
      electrical property tomography (MREPT), which occurred along the tissue
      interfaces. Transmitted magnetic fields B1+ were acquired at 3 T using a birdcage
      coil loaded with a phantom consisting of various adjacent tissues. Homogeneous
      Helmholtz was employed to calculate the EP maps by Laplacian computation of
      central differences. The maps of absolute REs (aREs) and relative REs (rREs) were
      calculated. The maximum and mean rREs, in addition to rRE distributions at the
      interfaces, were presented. Reconstructed EP maps showed various REs along
      different interface boundaries. Among all the investigated tissue interfaces, the
      kidney-fat interface presented the maximum mean rREs for both conductivity and
      relative permittivity. The minimum mean rRE of conductivity was observed at the
      spleen-muscle interface, and the minimum mean rRE of relative permittivity was
      detected along the lung-heart interface. The mean rREs ranged from 0.3986 to
      36.11 for conductivity and 0.2218 to 11.96 for relative permittivity. Overall,
      this research indicates that different REs occur at various tissue boundaries, as
      shown by the currently popular algorithm of MREPT. Thus, REs should be considered
      when applying MREPT to reconstruct the EP distributions inside the human body.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037716
TI  - Editorial.

PMID- 27037717
TI  - Detailed modeling of palpebral fissure and its influence on SAR and temperature
      rise in human eye under GHz exposures.
AB  - This article investigates variations in specific absorption rate and temperature
      rise in human eye caused by changes in palpebral fissure, the extent of opening
      between eyelids, under GHz plane-wave electromagnetic (EM) exposures. Detailed
      human head models with different palpebral fissure features were developed with a
      refined spatial resolution of 0.25 mm. These head models were then incorporated
      into both EM and bio-heat simulations, but using finite-difference time-domain
      method and finite-difference method, respectively. Maximum temperature rise in
      lens was found to be 0.8 degrees C under EM exposure at 100 W/m(2). Results
      reveal that changes in palpebral fissure would produce a 0.23 degrees C variation
      in maximum temperature rise in lens.

PMID- 27037718
TI  - Carbocations Confined in a Thiatriazuliporphyrin Frame.
AB  - In the search for tricarbaporphyrinoids, a three-component acid-catalyzed
      condensation of azulene, 2,5-bis[(p-tolyl)hydroxymethyl]thiophene, and an aryl
      aldehyde has been elaborated, affording the appropriate
      thiatriazuliporphyrinogens. The subsequent oxidation yielded a rare example of a
      macrocyclic organic tetracation, which can be readily and reversibly converted
      into macrocyclic tri- and dicarbocations by addition of one or two hydroxides
      bound at the meso position(s). Further insight into the influence of carbocation
      formation on the geometry, electronic structure, and magnetic manifestation in
      (1) H NMR spectroscopy has been obtained by using density functional theory
      calculations. The charge distribution was evaluated by mapping electron density
      surfaces with electrostatic potential (ESP).

PMID- 27037719
TI  - A novel technique in mouse liver transplantation.

PMID- 27037721
TI  - Robotic transmural ablation of bladder tumors using high-intensity focused
      ultrasound: Experimental study.
AB  - OBJECTIVES: To evaluate the feasibility of robot-assisted laparoscopic high
      intensity focused ultrasound for targeted, extravesical, transmural, full
      thickness ablation of intact bladder wall and tumor. METHODS: In three fresh
      cadavers and one acute porcine model, the transperitoneal robotic approach was
      used to mobilize the bladder and create a midline cystotomy. "Mimic" bladder
      tumors (2 tumors/case) were created by robotically suturing a piece of striated
      muscle (2.5 * 2.5 cm) to the luminal, urothelial surface of the bladder wall. The
      cystotomy was suture-repaired and bladder distended with 250 mL saline. A
      laparoscopic high-intensity focused ultrasound probe was robotically placed
      extravesically in direct contact with the serosal surface of the bladder wall to
      image the "mimic" tumor. Targeted, transmural, full-thickness high-intensity
      focus ultrasound ablation of the "mimic" tumor and adjacent bladder was carried
      out under real-time ultrasound and robotic monitoring. Untreated areas of the
      bladder served as a comparison. Post-procedure, gross and microscopic
      examinations were carried out. RESULTS: Laparoscopic high-intensity focused
      ultrasound ablation was feasible for all "mimic" tumors (100%). Real-time
      ultrasound clearly visualized the "mimic" tumor. Simultaneous display of the pre
      planning and real-time treatment ultrasound images confirmed targeting precision.
      Mean operative room times for ultrasound localization, laparoscopic high
      intensity focused ultrasound probe coupling, high-intensity focus ultrasound
      ablation, and total procedure were 3, 5, 6 and 60 min, respectively. On necropsy,
      no thermal/mechanical injuries occurred to the untreated bladder wall, adjacent
      organs or ureters. Gross inspection distinguished the treated from untreated
      areas. Histopathology confirmed sharply demarcated thermal coagulative necrosis
      and shrinkage effects between the treated and untreated areas. CONCLUSIONS:
      Laparoscopic extravesical high-intensity focus ultrasound for transmural, full
      thickness targeted ablation of intact bladder wall and tumor is feasible. This
      has implications for bladder-sparing surgery in select patients with solitary
      muscle-invasive bladder cancer.

PMID- 27037720
TI  - Incorporating dixon multi-echo fat water separation for novel quantitative
      magnetization transfer of the human optic nerve in vivo.
AB  - PURPOSE: The optic nerve (ON) represents the sole pathway between the eyes and
      brain; consequently, diseases of the ON can have dramatic effects on vision.
      However, quantitative magnetization transfer (qMT) applications in the ON have
      been limited to ex vivo studies, in part because of the fatty connective tissue
      that surrounds the ON, confounding the magnetization transfer (MT) experiment.
      Therefore, the aim of this study was to implement a multi-echo Dixon fat-water
      separation approach to remove the fat component from MT images. METHODS: MT
      measurements were taken in a single slice of the ON and frontal lobe using a
      three-echo Dixon readout, and the water and out-of-phase images were applied to a
      two-pool model in ON tissue and brain white matter to evaluate the effectiveness
      of using Dixon fat-water separation to remove fatty tissue from MT images.
      RESULTS: White matter data showed no significant differences between image types;
      however, there was a significant increase (p < 0.05) in variation in the out-of
      phase images in the ON relative to the water images. CONCLUSIONS: The results of
      this study demonstrate that Dixon fat-water separation can be robustly used for
      accurate MT quantification of anatomies susceptible to partial volume effects
      resulting from fat. Magn Reson Med 77:707-716, 2017. (c) 2016 International
      Society for Magnetic Resonance in Medicine.

PMID- 27037722
TI  - Telehealth to improve asthma control in pregnancy: A randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Poorly controlled asthma during pregnancy is hazardous
      for both mother and foetus. Better asthma control may be achieved if patients are
      involved in regular self-monitoring of symptoms and self-management according to
      a written asthma action plan. Telehealth applications to optimize asthma
      management and outcomes in pregnant women have not yet been evaluated. This study
      evaluated the efficacy of a telehealth programme supported by a handheld
      respiratory device in improving asthma control during pregnancy. METHODS:
      Pregnant women with asthma (n = 72) from two antenatal clinics in Melbourne,
      Australia, were randomized to one of two groups: (i) intervention-involving a
      telehealth programme (management of asthma with supportive telehealth of
      respiratory function in pregnancy (MASTERY((c)) )) supported by a handheld
      respiratory device and an Android smart phone application (Breathe-easy((c)) )
      and written asthma action plan or (ii) control-usual care. The primary outcome
      was change in asthma control at 3 and 6 months (prenatal). Secondary outcomes
      included changes in quality of life and lung function, and perinatal/neonatal
      outcomes. RESULTS: At baseline, participants' mean (+/- standard deviation) age
      was 31.4 +/- 4.5 years and gestational age 16.7 +/- 3.1 weeks. At 6 months, the
      MASTERY group had better asthma control (P = 0.02) and asthma-related quality of
      life (P = 0.002) compared with usual care. There were no significant differences
      between groups in lung function, unscheduled health-care visits, days off
      work/study, oral corticosteroid use, or perinatal outcomes. Differences between
      groups were not significant at 3 months. CONCLUSION: Telehealth interventions
      supporting self-management are feasible and could potentially improve asthma
      control and asthma-related quality of life during pregnancy.

PMID- 27037723
TI  - Co-occurrence of myasthenia gravis with Parkinson's disease: A not to be missed
      diagnosis.

PMID- 27037724
TI  - Emotional satisfaction index for dementia patients.

PMID- 27037725
TI  - Fatigue as a clinical sign of biological aging: exploratory analyses from the
      MINDED project.

PMID- 27037726
TI  - Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness
      and outcomes: a multi-institutional study.
AB  - Monocyte-derived cells, constituents of the cancer microenvironment, support
      chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell
      interaction and secreted factors. We hypothesized that circulating absolute
      monocyte count (AMC) reflects the monocyte-derived cells in the microenvironment,
      and that higher AMC is associated with increased CLL cell survival in vivo and
      thus inferior CLL patient outcomes. We assessed the extent to which AMC at
      diagnosis of CLL is correlated with clinical outcomes, and whether this
      information adds to currently used prognostic markers. We evaluated AMC,
      clinically used prognostic markers, and time to event data from 1,168 CLL
      patients followed at the Mayo Clinic, the Duke University Medical Center, and the
      Durham VA Medical Center. Elevated AMC was significantly associated with inferior
      clinical outcomes, including time to first therapy (TTT) and overall survival
      (OS). AMC combined with established clinical and molecular prognostic markers
      significantly improved risk-stratification of CLL patients for TTT. As an
      elevated AMC at diagnosis is associated with accelerated disease progression, and
      monocyte-derived cells in the CLL microenvironment promote CLL cell survival and
      proliferation, these findings suggest that monocytes and monocyte-derived cells
      are rational therapeutic targets in CLL. Am. J. Hematol. 91:687-691, 2016. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27037727
TI  - Pressure and judgement within a dichotomous landscape of infant feeding: a
      grounded theory study to explore why breastfeeding women do not access peer
      support provision.
AB  - Lack of support is reported as a key reason for early breastfeeding cessation.
      While breastfeeding peer support (BPS) is a recommended intervention to increase
      breastfeeding rates, a number of studies identify that engagement with BPS is
      problematic. Due to paucity of research in this area, this study explores why
      breastfeeding women do not access BPS in South-West England. Utilising a
      constructionist grounded theory approach, 33 participants (women (n = 13), health
      professionals (n = 6) and peer supporters (n = 14)) participated in a semi
      structured interview (n = 22) or focus group (n = 11). Analysis involved open
      coding, constant comparisons and focussed coding. One core category and three
      main themes explicating non-access were identified. The core category concerns
      women's experiences of pressure and judgement around their feeding decisions
      within a dichotomous landscape of infant feeding language and support. Theme one,
      'place and space of support', describes the contrast between perceived pressure
      to breastfeed and a lack of adequate and appropriate support. Theme two, 'one way
      or no way', outlines the rules-based approach to breastfeeding adopted by some
      health professionals and how women avoided BPS due to anticipating a similar
      approach. Theme three, 'it must be me', concerns how lack of embodied insights
      could lead to 'breastfeeding failure' identities. A background of dichotomised
      language, pressure and moral judgement, combined with the organisation of post
      natal care and the model of breastfeeding adopted by health professionals, may
      inhibit women's access to BPS. A socio-cultural model of breastfeeding support
      providing clear messages regarding the value and purpose of BPS should be
      adopted.

PMID- 27037728
TI  - Host genetic influence on papillomavirus-induced tumors in the horse.
AB  - The common equine skin tumors known as sarcoids have been causally associated
      with infection by bovine papillomavirus (BPV). Additionally, there is evidence
      for host genetic susceptibility to sarcoids. We investigated the genetic basis of
      susceptibility to sarcoid tumors on a cohort of 82 affected horses and 270
      controls genotyped on a genome-wide platform and two custom panels. A Genome Wide
      Association Study (GWAS) identified candidate regions on six chromosomes.
      Bayesian probability analysis of the same dataset verified only the regions on
      equine chromosomes (ECA) 20 and 22. Fine mapping using custom-produced SNP arrays
      for ECA20 and ECA22 regions identified two marker loci with high levels of
      significance: SNP BIEC2-530826 (map position 32,787,619) on ECA20 in an intron of
      the DQA1 gene in the Major Histocompatibility Complex (MHC) class II region (p =
      4.6e-06), and SNP BIEC2-589604 (map position 25,951,536) on ECA22 in a 200 kb
      region containing four candidate genes: PROCR, EDEM2, EIF6 and MMP24 (p = 2.14e
      06). The marker loci yielded odds ratios of 5.05 and 4.02 for ECA20 and ECA22,
      respectively. Associations between genetic MHC class II variants and
      papillomavirus-induced tumors have been reported for human papillomavirus and
      cottontail rabbit papillomavirus infections. This suggests a common mechanism for
      susceptibility to tumor progression that may involve subversion of the host
      immune response. This study also identified a genomic region other than MHC that
      influenced papillomavirus-induced tumor development in the studied population.

PMID- 27037729
TI  - A cost and clinical effectiveness analysis among moist wound healing dressings
      versus traditional methods in home care patients with pressure ulcers.
AB  - The aim of the study was a cost and clinical effectiveness analysis between moist
      wound healing dressings and gauze in a homecare set up for the treatment of stage
      III and IV pressure ulcers up to complete healing. In addition, we assessed the
      overall economic burden on the Healthcare System. Treatment method for each
      patient was chosen randomly by using sealed opaque envelopes. The authors
      monitored the healing progress and recorded treatment costs without interfering
      with the treatment process. The healing progress was estimated by using surface
      measurement transparent films. To estimate treatment costs, the authors took into
      account labor costs, cost of dressings, as well the cost of other materials such
      as cleansing gauzes, normal saline, syringes, examination gloves, antiseptics and
      adhesive tape. The patient group under treatment with moist wound healing
      dressings consisted of 27 men and 20 women aged 75.1 +/- 8,6 and had an average
      ulcer surface of 43.5 +/- 30.70 cm(2) ; the patient group under treatment with
      gauze comprised 25 men and 23 women aged 77.02 +/- 8.02 and had an average ulcer
      surface 41.52 +/- 29.41 cm(2) (p = 0.25, 95% CI, Student's t test). The average
      healing time for the moist wound healing dressings group' was 85.56 +/- 52.09
      days, while 121.4 +/- 52.21 days for the "gauze group" (p = 0.0001, 95% CI,
      Student's t test). The dressing change frequency per patient was reduced in the
      "moist wound healing dressings group," 49.5 +/- 29.61, compared with a dressing
      change frequency per patient of 222.6 +/- 101.86 for the "gauze group" (p =
      0.0001, 95% CI, Student's t test). The use of moist wound healing dressings had a
      lower total treatment cost of 1,351 ? per patient compared with, the use of
      gauzes (3,888 ?).

PMID- 27037730
TI  - Research challenges for drug-induced birth defects.
AB  - Drug-induced birth defects (teratogenesis) represent unique adverse drug
      reactions (ADRs). Not only is the ADR manifest in a subject other than the one
      for whom treatment is intended, but most teratogens can be identified only after
      a drug is marketed. We know little about fetal safety for most marketed drugs,
      and identification of potential teratogens uniquely requires that study designs
      consider issues related to the effects of specific drugs, specific defects, and
      specific gestational timing.

PMID- 27037731
TI  - Synthesizing 2D and 3D Selenidostannates in Ionic Liquids: The Synergistic
      Structure-Directing Effects of Ionic Liquids and Metal-Amine Complexes.
AB  - Presented are the ionothermal syntheses, characterizations, and properties of a
      series of two- and three-dimensional selenidostannate compounds synergistically
      directed by metal-amine complex (MAC) cations and ionic liquids (ILs) of
      [Bmmim]Cl (Bmmim=1-butyl-2,3-dimethylimidazolium). Four selenidostannates,
      namely, 2D-(Bmmim)3 [Ni(en)3 ]2 [Sn9 Se21 ]Cl (1, en=ethylenediamine), 2D
      (Bmmim)8 [Ni2 (teta)2 (MU-teta)]Sn18 Se42 (2, teta=triethylenetetramine), 2D
      (Bmmim)4 [Ni(tepa)Cl]2 [Ni(tepa)Sn12 Se28 ] (3, tepa=tetraethylenepentamine), and
      3D-(Bmmim)2 [Ni(1,2-pda)3 ]Sn8 Se18 (4, 1,2-pda=1,2-diaminopropane), were
      obtained. Single-crystal X-ray diffraction analyses revealed that compounds 1 and
      2 possess a lamellar anionic [Sn3 Se7 ]n (2n-) structure comprising distinct
      eight-membered ring units, whereas 3 features a MAC-decorated anionic
      [Ni(tepa)Sn12 Se28 ]n (6n-) layered structure. In contrast to 1-3, compound 4
      exhibits a 3D open framework of anionic [Sn4 Se9 ]n (2n-) . The structural
      variation from 1 to 4 clearly indicates that on the basis of the synergistic
      structure-directing ability of the MACs and ILs, variation of the organic
      polyamine ligand has a significant impact on the formation of selenidostannates.

PMID- 27037732
TI  - Patient-physician communication and health-related quality of life of patients
      with localised prostate cancer undergoing radical prostatectomy - a longitudinal
      multilevel analysis.
AB  - OBJECTIVES: To examine whether patient-physician communication is associated with
      health-related quality of life (HRQoL) in a sample of patients with localised
      prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS:
      HAROW (Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful
      Waiting) is a prospective, observational study designed to collect data of the
      different treatment options for newly diagnosed patients with localised prostate
      cancer under real-life conditions. At 6-months intervals, clinical data (D'Amico
      risk categories, Charlson comorbidity index), aspects of patient-provider
      communication (standardised psychosocial-care instrument for patients' assessment
      of communication; Cologne Patient Questionnaire), and HRQoL (European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire)
      were assessed. Data were analysed by longitudinal multilevel analysis. RESULTS:
      Completed questionnaires for 1772 patients undergoing a RP were analysed over a 3
      year follow-up period. Patients rated the patient-provider communication
      generally high with slight variations over the course of treatment (3.2-3.8). The
      HRQoL of the patients varied substantial over time and between the reported
      subscales (global HRQoL 71.1-77.2; physical functioning 89.1-92.1; role
      functioning 81.0-88.1; emotional functioning 74.4-84.0; cognitive functioning
      84.3-87.7; social functioning (77.7-84.0). The longitudinal multilevel models
      showed significant associations between patient-provider communication in terms
      of devotion, support and shared decision-making, and functional aspects of HRQoL.
      CONCLUSION: Patient-provider communication is a valuable resource to support
      patients with prostate cancer coping with the disease and to improve their HRQoL.
      Future interventions should be designed especially for urologists to enhance
      their awareness for the importance of communication and the relationship with
      their patients with prostate cancer for treatment outcomes.

PMID- 27037733
TI  - Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse:
      A systematic review of the case literature.
AB  - BACKGROUND/OBJECTIVES: Nitrous oxide (N2 O) is known to have abuse potential,
      although debate regarding the toxic effects of such abuse continues. Our
      objective was to review the case literature and present the neurologic,
      psychiatric and medical consequences of N2 O abuse. METHODS: A systematic
      literature review was completed for case reports using keywords "nitrous oxide"
      with "abuse/abusing" or "misuse/misusing" or "overuse/overusing" or "addiction."
      Non-English-language cases and cases not involving direct toxic effects of N2 O
      were excluded as were commentaries or personal essays. Clinical presentation,
      frequency of N2 O abuse, laboratory studies, imaging, ancillary tests, treatments
      and outcomes were collected from case reports. RESULTS: Our review returned 335
      Pubmed, 204 Web of Science, 73 PsycINFO, 6 CINAHL, 55 EMBASE and 0 Grey
      Literature results, and after exclusion and removal of duplicates, 91 individual
      cases across 77 publications were included. There were also 11 publications
      reporting 29 cases of death related to N2 O abuse. The majority of cases (N = 72)
      reported neurologic sequelae including myeloneuropathy and subacute combined
      degeneration, commonly (N = 39) with neuroimaging changes. Psychiatric (N = 11)
      effects included psychosis while other medical effects (N = 8) included
      pneumomediastinum and frostbite. Across all cases N2 O abuse was correlated with
      low or low-normal Vitamin B12 (cyanocobalamin) levels (N = 52) and occasionally
      elevated homocysteine and methylmalonic acid. CONCLUSIONS/SCIENTIFIC
      SIGNIFICANCE: N2 O abuse represents a significant problem because of the
      difficulty involved with identification and the toxicity related to chronic abuse
      including possible death. Health professionals should be aware of the toxic
      effects of N2 O and be able to identify potential N2 O abuse. (Am J Addict
      2016;25:358-369).

PMID- 27037735
TI  - Loop-Grafted Old Yellow Enzymes in the Bienzymatic Cascade Reduction of Allylic
      Alcohols.
AB  - The enzymatic reduction of C=C bonds in allylic alcohols with Old Yellow Enzymes
      represents a challenging task, due to insufficient activation through the hydroxy
      group. In our work, we coupled an alcohol dehydrogenase with three wild-type ene
      reductases-namely nicotinamide-dependent cyclohex-2-en-1-one reductase (NCR) from
      Zymomonas mobilis, OYE1 from Saccharomyces pastorianus and morphinone reductase
      (MR) from Pseudomonas putida M10-and four rationally designed beta/alpha loop
      variants of NCR in the bienzymatic cascade hydrogenation of allylic alcohols.
      Remarkably, the wild type of NCR was not able to catalyse the cascade reaction
      whereas MR and OYE1 demonstrated high to excellent activities. Through the
      rational loop grafting of two intrinsic beta/alpha surface loop regions near the
      entrance of the active site of NCR with the corresponding loops from OYE1 or MR
      we successfully transferred the cascade reduction activity from one family member
      to another. Further we observed that loop grafting revealed certain influences on
      the interaction with the nicotinamide cofactor. 

PMID- 27037736
TI  - How Positive Is Their Future? Assessing the Role of Optimism and Social Support
      in Understanding Mental Health Symptomatology among Homeless Adults.
AB  - Optimism has been noted as a primary protective factor in understanding mental
      health symptomatology in clinical and non-clinical settings. Any exploration of
      optimism has been absent in understanding mental health outcomes among homeless
      people. This study, using intensive interviews with 168 homeless adults in
      Northwest Arkansas, examines the role that social support and optimism play in
      lessening the negative impact of homeless circumstances/experiences on mental
      health symptomatology. Using OLS, findings support a mediating/protective role
      that social support and optimism play in lowering the negative effects of
      childhood life experiences on depressive symptoms among homeless persons. Despite
      the overwhelming conditions of homelessness, persons with higher levels of
      optimism and social support report lower depression and anxiety symptoms. The
      findings are discussed paying particular attention to the importance of
      developing and maintaining the perception of support and resiliency in preserving
      a positive outlook for the future among homeless persons facing often
      debilitating circumstances. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037737
TI  - Protective benefit of predominant breastfeeding against otitis media may be
      limited to early childhood: results from a prospective birth cohort study.
AB  - OBJECTIVES: To examine the long-term effects of predominant breastfeeding on
      incidence of otitis media. DESIGN: Prospective birth cohort study. SETTING: The
      West Australian Pregnancy Cohort (Raine) Study recruited 2900 mothers through
      antenatal clinics at the major tertiary obstetric hospital in Perth, Western
      Australia, between 1989 and 1992. PARTICIPANTS: In total, 2237 children
      participated in a 6-year cohort follow-up, and a subset of 1344 were given ear
      and hearing assessments. MAIN OUTCOME MEASURES: OM diagnosis at 6 years of age
      (diagnosed by low-compliance tympanograms, 0-0.1 mmho). This was compared to OM
      diagnosed at the 3-year cohort follow-up using parent-report measures. Main
      exposure measures were duration of predominant breastfeeding (defined as the age
      other milk was introduced) and duration of partial (any) breastfeeding (defined
      as the age breastfeeding was stopped). RESULTS: There was a significant,
      independent association between predominant breastfeeding (OR = 1.33 [1.04,
      1.69]; P = 0.02) and OM, and breastfeeding duration (OR = 1.35 [1.08, 1.68]; P =
      0.01) with OM at 3 years of age. However, at 6 years of age, this relationship
      was no longer statistically significant (predominant breastfeeding OR = 0.78
      [0.48, 1.06]; P = 0.09; duration of breastfeeding, OR = 1.34 [0.81, 2.23]; P =
      0.25). CONCLUSIONS: Our findings are in line with a number of epidemiological
      studies which show a positive association between breastfeeding and OM in early
      childhood. However, the long-term follow-up of these children revealed that by 6
      years of age, there was no significant influence of breastfeeding on presence of
      OM. These results suggest that the protective effect of predominant breastfeeding
      for at least 6 months does not extend to school-age children, where other social
      and environmental factors may be stronger predictors of OM.

PMID- 27037738
TI  - Nurse practitioners' job satisfaction in rural versus nonrural areas.
AB  - PURPOSE: The purpose of this study is to examine the nature of nurse
      practitioners' (NPs) job satisfaction and its relationship to work conditions in
      rural versus nonrural areas. DATA SOURCES: A secondary analysis of data extracted
      from the 2012 National Sample Survey of Nurse Practitioners. NPs in active
      practice in clinical settings were included in this study. The final analytic
      sample consisted of 9010 NPs. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Overall,
      NPs were satisfied with their positions (satisfied to very satisfied). Both rural
      and nonrural NPs were most satisfied with the proportion of their time spent in
      patient care, their level of autonomy, and the respect that they received from
      other colleagues. Nonrural NPs who said or stated that they performed to the
      fullest extent of their states' legal scope of practice were more satisfied than
      nonrural NPs who did not. When nonrural NPs fully utilized their NP skills, their
      job satisfaction increased. For rural NPs, a similar pattern was found regarding
      full use of their NP skills. The evidence found in this study reminds us that
      given the increasing demands for NPs' healthcare services, continuous effort
      should be made to recruit and retain rural NPs.

PMID- 27037739
TI  - Short bowel syndrome (SBS)-associated alterations within the gut-liver axis
      evolve early and persist long-term in the piglet model of short bowel syndrome.
AB  - BACKGROUND AND AIM: Short bowel syndrome (SBS) is primarily characterized by
      malabsorption and malnutrition, resulting from loss of intestinal absorptive area
      following massive small bowel resection (SBR). Bile acids and the gut microbiota
      are functionally linked within the gut-liver axis; however, SBS-associated
      disturbances within the gut-liver axis remain largely unexplored. The aim of this
      study was to characterize the evolution of bile acid alterations within the gut
      liver axis at both short-term and long-term time points and to relate these
      changes to alterations in colonic bacterial composition. METHODS: Four-week-old
      piglets were assigned to 75% SBR, sham-operation or non-operation control groups.
      High throughput sequencing was employed to determine bacterial abundance in
      colonic content and ultra-performance liquid chromatography used to determine the
      bile acid concentration of gall bladder, portal serum, and fecal samples.
      RESULTS: Bile acid complexity and relative abundance are altered in the SBS
      piglet model at two weeks post-SBR, and these changes persisted at six weeks post
      SBR. Our examination of the microbial profile revealed an early and persistent
      loss in bacteria belonging to the Clostridiales order. CONCLUSIONS: This study
      provides evidence of an early and persistent disturbance of the bile acid profile
      throughout the entero-hepatic circulation with an increase in the proportion of
      primary bile acids and a decrease in secondary bile acids following SBR. These
      changes were associated with a loss of bacteria belonging to the Clostridiales
      order consistent with a disturbance in the bile-microbial axis following SBR.

PMID- 27037740
TI  - Bending over forwards - to make a diagnosis.

PMID- 27037741
TI  - Spatiotemporal variation of nitrate uptake kinetics within the maize (Zea mays
      L.) root system is associated with greater nitrate uptake and interactions with
      architectural phenes.
AB  - Increasing maize nitrogen acquisition efficiency is a major goal for the 21st
      century. Nitrate uptake kinetics (NUK) are defined by I max and K m, which denote
      the maximum uptake rate and the affinity of transporters, respectively. Because
      NUK have been studied predominantly at the molecular and whole-root system
      levels, little is known about the functional importance of NUK variation within
      root systems. A novel method was created to measure NUK of root segments that
      demonstrated variation in NUK among root classes (seminal, lateral, crown, and
      brace). I max varied among root class, plant age, and nitrate deprivation
      combinations, but was most affected by plant age, which increased I max, and
      nitrate deprivation time, which decreased I max K m was greatest for crown roots.
      The functional-structural simulation SimRoot was used for sensitivity analysis of
      plant growth to root segment I max and K m, as well as to test interactions of I
      max with root system architectural phenes. Simulated plant growth was more
      sensitive to I max than K m, and reached an asymptote near the maximum I max
      observed in the empirical studies. Increasing the I max of lateral roots had the
      largest effect on shoot growth. Additive effects of I max and architectural
      phenes on nitrate uptake were observed. Empirically, only lateral root tips aged
      20 d operated at the maximum I max, and simulations demonstrated that increasing
      all seminal and lateral classes to this maximum rate could increase plant growth
      by as much as 26%. Therefore, optimizing I max for all maize root classes merits
      attention as a promising breeding goal.

PMID- 27037742
TI  - Metachronous T-Lymphoblastic Lymphoma and Burkitt Lymphoma in a Child With
      Constitutional Mismatch Repair Deficiency Syndrome.
AB  - Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition
      syndrome associated with a high risk of developing early-onset malignancies of
      the blood, brain, and intestinal tract. We present the case of a patient with T
      lymphoblastic lymphoma at the age of 3 years, followed by Burkitt lymphoma 10
      years later. This patient also exhibited numerous nonmalignant findings including
      cafe au lait spots, lipomas, bilateral renal nodules, a nonossifying fibroma,
      multiple colonic adenomas, and a rapidly enlarging pilomatrixoma. The spectrum of
      malignant and nonmalignant neoplasms in this patient highlights the remarkable
      diversity, and early onset, of lesions seen in children with CMMRD.

PMID- 27037743
TI  - Early catheterization after initiation of extracorporeal membrane oxygenation
      support in children is associated with improved survival.
AB  - OBJECTIVES: The study evaluated the institutional experience with cardiac
      catheterization on extracorporeal membrane oxygenation (ECMO) support.
      BACKGROUND: There is scant literature on the outcomes of catheterization on ECMO.
      METHODS: A retrospective review was performed of all children who underwent
      catheterization on ECMO from 2003 to 2013. Patients were categorized as
      cardiomyopathy (CM) or congenital heart disease (CHD). RESULTS: During the study
      period, 215 children were placed on cardiac ECMO. Of these, 29.8% underwent 75
      catheterization procedures while on ECMO support. The median age of the cohort
      was 1.5 months (range 0 days -16.7 years) and the median weight was 3.9 kg (2.2
      63.1 kg). CM patients constituted 18.8% of the cohort and all of them underwent
      atrial septoplasty (an atrial septal stent in 7/12 and balloon atrial septoplasty
      or septostomy in 5). The survival to hospital discharge rate was 83% and the
      transplant-free survival rate was 58.3%. CHD patients constituted 81.2% of the
      cohort. In this group, transcatheter interventions were performed in 40.4% and
      subsequent surgical interventions in 40.4%. Survival to hospital discharge rate
      was 34.6% and transplant free survival rate was 32.7%. Overall, 76.7% underwent
      transcatheter or surgical interventions. The major catheterization complication
      rate was 6.7%. The mean ECMO-to-catheterization time was 1.6 days for survivors
      and 3.5 days for non-survivors (P = 0.034). Survival to discharge was better for
      the CM group compared to the CHD group (P = 0.01). Among CHD, survival was better
      with transcatheter interventions compared to no interventions or surgical
      interventions (P < 0.001). CONCLUSIONS: Cardiac catheterization and transcatheter
      interventions on ECMO can be performed with low rate of complications.
      Catheterization was associated with high rate of interventions. Better survival
      to hospital discharge was associated with transcatheter interventions, earlier
      performance of catheterization after ECMO and diagnosis of CM. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27037744
TI  - Defender-Attacker Decision Tree Analysis to Combat Terrorism.
AB  - We propose a methodology, called defender-attacker decision tree analysis, to
      evaluate defensive actions against terrorist attacks in a dynamic and hostile
      environment. Like most game-theoretic formulations of this problem, we assume
      that the defenders act rationally by maximizing their expected utility or
      minimizing their expected costs. However, we do not assume that attackers
      maximize their expected utilities. Instead, we encode the defender's limited
      knowledge about the attacker's motivations and capabilities as a conditional
      probability distribution over the attacker's decisions. We apply this methodology
      to the problem of defending against possible terrorist attacks on commercial
      airplanes, using one of three weapons: infrared-guided MANPADS (man-portable air
      defense systems), laser-guided MANPADS, or visually targeted RPGs (rocket
      propelled grenades). We also evaluate three countermeasures against these
      weapons: DIRCMs (directional infrared countermeasures), perimeter control around
      the airport, and hardening airplanes. The model includes deterrence effects, the
      effectiveness of the countermeasures, and the substitution of weapons and targets
      once a specific countermeasure is selected. It also includes a second stage of
      defensive decisions after an attack occurs. Key findings are: (1) due to the high
      cost of the countermeasures, not implementing countermeasures is the preferred
      defensive alternative for a large range of parameters; (2) if the probability of
      an attack and the associated consequences are large, a combination of DIRCMs and
      ground perimeter control are preferred over any single countermeasure.

PMID- 27037745
TI  - Genetic or epigenetic regulations in immune responses and allergic diseases.

PMID- 27037746
TI  - Pelvic floor muscle function, pelvic floor dysfunction and diastasis recti
      abdominis: Prospective cohort study.
AB  - AIMS: Compare vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength,
      and endurance in women with and without diastasis recti abdominis at gestational
      week 21 and at 6 weeks, 6 months, and 12 months postpartum. Furthermore, to
      compare prevalence of urinary incontinence (UI) and pelvic organ prolapse (POP)
      in the two groups at the same assessment points. METHODS: This is a prospective
      cohort study following 300 nulliparous pregnant women giving birth at a public
      university hospital. VRP, PFM strength, and endurance were measured with vaginal
      manometry. ICIQ-UI-SF questionnaire and POP-Q were used to assess UI and POP.
      Diastasis recti abdominis was diagnosed with palpation of  >=2 fingerbreadths 4.5
      cm above, at, or 4.5 cm below the umbilicus. RESULTS: At gestational week 21
      women with diastasis recti abdominis had statistically significant greater VRP
      (mean difference 3.06 cm H2 O [95%CI: 0.70; 5.42]), PFM strength (mean difference
      5.09 cm H2 O [95%CI: 0.76; 9.42]) and PFM muscle endurance (mean difference 47.08
      cm H2 O sec [95%CI: 15.18; 78.99]) than women with no diastasis. There were no
      statistically significant differences between women with and without diastasis in
      any PFM variables at 6 weeks, 6 months, and 12 months postpartum. No significant
      difference was found in prevalence of UI in women with and without diastasis at
      any assessment points. Six weeks postpartum 15.9% of women without diastasis had
      POP versus 4.1% in the group with diastasis (P = 0.001). CONCLUSIONS: Women with
      diastasis were not more likely to have weaker PFM or more UI or POP. Neurourol.
      Urodynam. 36:716-721, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037747
TI  - Leishmaniasis in Turkey: first clinical isolation of Leishmania major from 18
      autochthonous cases of cutaneous leishmaniasis in four geographical regions.
AB  - OBJECTIVE: To report isolation of Leishmania major strains obtained from 18
      Turkish autochthonous cutaneous leishmaniasis (CL) patients infected with L.
      major between 2011 and 2014. METHODS: Initial diagnosis relied on microscopy and
      culture in enriched medium, prepared by adding specific amounts of liver extract,
      protein and lipid sources to NNN medium. Promastigotes were then transferred to
      RPMI medium including 10% of foetal calf serum for mass culture. Species-specific
      real-time PCR targeting ITS1 region of Leishmania spp. was performed using both
      lesion aspiration samples and cultured promastigotes. Two of 18 isolates were
      identified by isoenzyme analysis in the Leishmaniasis Reference Center in
      Montpellier, France. Each isolate was inoculated into the footpads of six mice to
      observe the pathogenicity of L. major. Developing lesions were observed, and the
      thickening of footpads was measured weekly. RESULTS: Melting curve analyses of 18
      isolates showed a peak concordant with L. major, and two of them were confirmed
      by isoenzyme analyses as L. major zymodeme MON103. In the mouse model, acute
      lesions seen on day 21 were accepted as an indication of heavy infection. Severe
      impairments were observed on all mouse footpads over 3 weeks, which even
      progressed to extremity amputation. CONCLUSION: Cutaneous leishmaniasis-causing
      L. major was recently identified in Adana province in southern Turkey, with PCR.
      Our study shows that such CL cases are not limited to Adana but currently present
      from western to Southeastern Anatolia, and along the Mediterranean coast. The
      role of small mammals, the main reservoirs of L. major in Anatolia, needs to be
      elucidated, as do the underlying factors that cause severe clinical
      manifestations in L. major infections in Turkey, contrary to the infections in
      neighbouring countries.

PMID- 27037748
TI  - Hormone resuscitation therapy for brain-dead donors - is insulin beneficial or
      detrimental?
AB  - Hormonal replacement therapy to brain-dead potential organ donors remains
      controversial. A retrospective study was carried out of hormonal therapy on
      procurement of organs in 63 593 donors in whom information on thyroid hormone
      therapy (triiodothyronine or levothyroxine [T3 /T4 ]) was available. In 40 124
      donors, T3 /T4 and all other hormonal therapy were recorded. The percentage of
      all organs procured, except livers, was greater when T3 /T4 had been
      administered. An independent beneficial effect of antidiuretic hormone (ADH) was
      also clear. Corticosteroids were less consistently beneficial (most frequently
      when T3 /T4 had not been administered), although never detrimental. Insulin was
      almost never beneficial and at times was associated with a reduced yield of
      organs, particularly of the pancreas and intestine, an observation that does not
      appear to have been reported previously. In addition, there was reduced survival
      at 12 months of recipients of pancreases from T3 /T4 -treated donors, but not of
      pancreas grafts. The possibly detrimental effect observed following insulin
      therapy is discussed.

PMID- 27037749
TI  - Can medical students accurately predict their learning? A study comparing
      perceived and actual performance in neuroanatomy.
AB  - It is important that clinicians are able to adequately assess their level of
      knowledge and competence in order to be safe practitioners of medicine. The
      medical literature contains numerous examples of poor self-assessment accuracy
      amongst medical students over a range of subjects however this ability in
      neuroanatomy has yet to be observed. Second year medical students attending
      neuroanatomy revision sessions at the University of Southampton and the
      competitors of the National Undergraduate Neuroanatomy Competition were asked to
      rate their level of knowledge in neuroanatomy. The responses from the former
      group were compared to performance on a ten item multiple choice question
      examination and the latter group were compared to their performance within the
      competition. In both cohorts, self-assessments of perceived level of knowledge
      correlated weakly to their performance in their respective objective knowledge
      assessments (r = 0.30 and r = 0.44). Within the NUNC, this correlation improved
      when students were instead asked to rate their performance on a specific
      examination within the competition (spotter, rS = 0.68; MCQ, rS = 0.58). Despite
      its inherent difficulty, medical student self-assessment accuracy in neuroanatomy
      is comparable to other subjects within the medical curriculum. Anat Sci Educ 9:
      488-495. (c) 2016 American Association of Anatomists. 

PMID- 27037750
TI  - The Evolving, Multifaceted Roles of Autophagy in Cancer.
AB  - Autophagy is a lysosomal degradation process crucial for adaptation to stress and
      cellular homeostasis. In cancer, autophagy has been demonstrated to serve
      multifaceted roles in tumor initiation and progression. Although genetic evidence
      corroborates a role for autophagy as a tumor suppressor mechanism during tumor
      initiation, autophagy also sustains metabolic pathways in cancer cells and
      promotes survival within the harsh tumor microenvironment and in response to
      diverse anticancer therapies. Moreover, though traditionally viewed as an
      autodigestive process, more recent work demonstrates that autophagy also
      facilitates cellular secretion; the importance of these new functions of the
      autophagy pathway is being increasingly appreciated during cancer progression and
      treatment. In this review, we discuss how these evolving and diverse roles for
      autophagy both impede and promote tumorigenesis. 

PMID- 27037751
TI  - Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation:
      A Perfect Combination for Cancer Therapy.
AB  - Epigenetic silencing and inappropriate activation of gene expression are frequent
      events during the initiation and progression of cancer. These events involve a
      complex interplay between the hypermethylation of CpG dinucleotides within gene
      promoter and enhancer regions, the recruitment of transcriptional corepressors
      and the deacetylation and/or methylation of histone tails. These epigenetic
      regulators act in concert to block transcription or interfere with the
      maintenance of chromatin boundary regions. However, DNA/histone methylation and
      histone acetylation states are reversible, enzyme-mediated processes and as such,
      have emerged as promising targets for cancer therapy. This review will focus on
      the potential benefits and synergistic/additive effects of combining DNA
      demethylating agents and histone deacetylase inhibitors or lysine-specific
      demethylase inhibitors together in epigenetic therapy for solid tumors and will
      highlight what is known regarding the mechanisms of action that contribute to the
      antitumor response. 

PMID- 27037752
TI  - Emerging Roles of Epigenetic Regulator Sin3 in Cancer.
AB  - Revolutionizing treatment strategies is an urgent clinical need in the fight
      against cancer. Recently the scientific community has recognized chromatin
      associated proteins as promising therapeutic candidates. However, there is a need
      to develop more targeted epigenetic inhibitors with less toxicity. Sin3 family is
      one such target which consists of evolutionary conserved proteins with two
      paralogues Sin3A and Sin3B. Sin3A/B are global transcription regulators that
      provide a versatile platform for diverse chromatin-modifying activities. Sin3
      proteins regulate key cellular functions that include cell cycle, proliferation,
      and differentiation, and have recently been implicated in cancer pathogenesis. In
      this chapter, we summarize the key concepts of Sin3 biology and elaborate the
      recent advancements in the role of Sin3 proteins in cancer with specific examples
      in multiple endocrine neoplasia type 2, pancreatic ductal adenocarcinoma, and
      triple negative breast cancer. Finally, a program to create an integrative
      approach for screening antitumor agents that target chromatin-associated factors
      like Sin3 is presented. 

PMID- 27037753
TI  - PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future
      Oncobiology.
AB  - Since the initial recognition of a mechanistic role of p21-activated kinase 1
      (PAK1) in breast cancer invasion, PAK1 has emerged as one of the widely
      overexpressed or hyperactivated kinases in human cancer at-large, allowing the
      PAK family to make in-roads in cancer biology, tumorigenesis, and cancer
      therapeutics. Much of our current understanding of the PAK family in cancer
      progression relates to a central role of the PAK family in the integration of
      cancer-promoting signals from cell membrane receptors as well as function as a
      key nexus-modifier of complex, cytoplasmic signaling network. Another core aspect
      of PAK signaling that highlights its importance in cancer progression is through
      PAK's central role in the cross talk with signaling and interacting proteins, as
      well as PAK's position as a key player in the phosphorylation of effector
      substrates to engage downstream components that ultimately leads to the
      development cancerous phenotypes. Here we provide a comprehensive review of the
      recent advances in PAK cancer research and its downstream substrates in the
      context of invasion, nuclear signaling and localization, gene expression, and DNA
      damage response. We discuss how a deeper understanding of PAK1's pathobiology
      over the years has widened research interest to the PAK family and human cancer,
      and positioning the PAK family as a promising cancer therapeutic target either
      alone or in combination with other therapies. With many landmark findings and
      leaps in the progress of PAK cancer research since the infancy of this field
      nearly 20 years ago, we also discuss postulated advances in the coming decade as
      the PAK family continues to shape the future of oncobiology. 

PMID- 27037754
TI  - Sirtuins and the Estrogen Receptor as Regulators of the Mammalian Mitochondrial
      UPR in Cancer and Aging.
AB  - By being both the source of ATP and the mediator of apoptosis, the mitochondria
      are key regulators of cellular life and death. Not surprisingly alterations in
      the biology of the mitochondria have implications in a wide array of diseases
      including cancer and age-related diseases such as neurodegeneration. To protect
      the mitochondria against damage the mitochondrial unfolded protein response
      (UPR(mt)) orchestrates several pathways, including the protein quality controls,
      the antioxidant machinery, oxidative phosphorylation, mitophagy, and
      mitochondrial biogenesis. While several reports have implicated an array of
      transcription factors in the UPR(mt), most of the focus has been on studies of
      Caenorhabditis elegans, which led to the identification of ATFS-1, for which the
      mammalian homolog remains unknown. Meanwhile, there are studies which link the
      UPR(mt) to sirtuins and transcription factors of the Foxo family in both C.
      elegans and mammalian cells but those have been largely overlooked. This review
      aims at emphasizing the potential importance of these studies by building on the
      large body of literature supporting the key role of the sirtuins in the
      maintenance of the integrity of the mitochondria in both cancer and aging.
      Further, the estrogen receptor alpha (ERalpha) and beta (ERbeta) are known to
      confer protection against mitochondrial stress, and at least ERalpha has been
      linked to the UPR(mt). Considering the difference in gender longevity, this
      chapter also includes a discussion of the link between the ERalpha and ERbeta and
      the mitochondria in cancer and aging. 

PMID- 27037755
TI  - Keratinocyte Carcinoma as a Marker of a High Cancer-Risk Phenotype.
AB  - Keratinocyte carcinoma (KC) (also referred to as nonmelanoma skin cancer) is by
      far the most common form of human cancer. A personal history of KC is well
      established to be associated with increased risk of recurrent KC and malignant
      melanoma, a less common yet more fatal form of skin cancer. More surprising is
      that a substantial body of epidemiologic evidence now indicates that a personal
      history of KC is significantly associated with an overall elevated risk of
      noncutaneous malignancies. This association is not limited to one or a few types
      of cancer but applies across many different types of malignancy. This association
      has been consistently observed in prospective studies across genders for both
      major histologic types of KC, basal cell carcinoma and squamous cell carcinoma.
      The risk of other cancers has been even stronger in those with younger compared
      with older age of onset of KC. A robust body of evidence lends support to the
      notion that KC may be a marker of a high cancer-risk phenotype. The underlying
      mechanisms for this association remain to be elucidated, but the cross-cutting
      nature of this association across numerous malignancies suggests that research to
      uncover these mechanisms is a promising line of inquiry that could potentially
      yield valuable insight into human carcinogenesis. 

PMID- 27037756
TI  - Cardiomyopathy diagnosed in the eldest child harbouring p.S24X mutation in JUP.

PMID- 27037758
TI  - Synthesis of Indolophanes by Photochemical Macrocyclization.
AB  - Herein, we report the synthetically practical, short, and general access to novel
      indolophane architectures by means of a photochemical C-H activation process-the
      Witkop cyclization. These highly strained scaffolds were obtained by photoinduced
      ring closure and feature atropisomerism as well as aromatic ring current effects,
      which both have been investigated. The prevailing regioselectivity of theWitkop
      cyclization reaction was completely reversed by the presence of a quaternary
      carbon center, exerting a strong Thorpe-Ingold effect on the system for which
      experimental-evidence is provided. 

PMID- 27037757
TI  - Plant hydraulics as a central hub integrating plant and ecosystem function:
      meeting report for 'Emerging Frontiers in Plant Hydraulics' (Washington, DC, May
      2015).
AB  - Water plays a central role in plant biology and the efficiency of water transport
      throughout the plant affects both photosynthetic rate and growth, an influence
      that scales up deterministically to the productivity of terrestrial ecosystems.
      Moreover, hydraulic traits mediate the ways in which plants interact with their
      abiotic and biotic environment. At landscape to global scale, plant hydraulic
      traits are important in describing the function of ecological communities and
      ecosystems. Plant hydraulics is increasingly recognized as a central hub within a
      network by which plant biology is connected to palaeobiology, agronomy,
      climatology, forestry, community and ecosystem ecology and earth-system science.
      Such grand challenges as anticipating and mitigating the impacts of climate
      change, and improving the security and sustainability of our food supply rely on
      our fundamental knowledge of how water behaves in the cells, tissues, organs,
      bodies and diverse communities of plants. A workshop, 'Emerging Frontiers in
      Plant Hydraulics' supported by the National Science Foundation, was held in
      Washington DC, 2015 to promote open discussion of new ideas, controversies
      regarding measurements and analyses, and especially, the potential for expansion
      of up-scaled and down-scaled inter-disciplinary research, and the strengthening
      of connections between plant hydraulic research, allied fields and global
      modelling efforts.

PMID- 27037759
TI  - Targeting the Notch Pathway to Prevent Rejection.
AB  - Immune rejection is mediated by a complex interplay of cellular and humoral
      mechanisms. Current therapeutic strategies, which rely on global
      immunosuppression, can result in serious complications and are not completely
      effective. Notch signaling is a cell-to-cell communication pathway that plays an
      important role during T cell development and in the regulation of peripheral
      immune responses. Initial work, performed mainly through gain-of-function
      approaches, paradoxically identified Notch as an inducer of tolerance; however,
      recent studies using loss-of-function approaches in mouse models of transplant
      rejection and graft-versus-host disease have clarified an important role for
      Notch as a central mediator of T cell alloreactivity. Short-term inhibition of
      individual Notch ligands in the peritransplant period had long-lasting protective
      effects. In a vascularized heart allograft model, blockade of Delta-like Notch
      ligands dampened both cellular and humoral rejection. In this minireview, we
      summarize current knowledge about the role of Notch signaling during allograft
      rejection and provide an overarching mechanism through which Notch acts to
      promote T cell pathogenicity and allograft damage. We propose that targeting
      elements of the Notch pathway could provide a new therapeutic approach to prevent
      allograft rejection.

PMID- 27037760
TI  - Removal from liver transplantation list of a hepatitis C virus-HIV co-infected
      patient after successful treatment with sofosbuvir and daclatasvir.
AB  - We present a human immunodeficiency virus-infected patient with severe
      decompensated hepatitis C virus-related cirrhosis awaiting liver transplantation
      (LT) who received a 24-week course of interferon/ribavirin-free antiviral
      treatment with sofosbuvir and daclatasvir on a compassionate basis. Rapid viral
      suppression was associated with progressive improvement of his liver function
      tests. The patient achieved a sustained virological response and concomitant
      clinical improvement, which prompted removal from the LT list 12 weeks after the
      end of treatment.

PMID- 27037762
TI  - Effect of isovalent dopants on photodegradation ability of ZnS nanoparticles.
AB  - Isovalent (Mn, Cd, Cu, Co)-doped-ZnS nanoparticles having size vary in between 2
      to 5nm are synthesized by co-precipitation route. Their photocatalytic activity
      for decoloration of Cango Red and Malachite Green dyes is tested in visible
      radiation under natural conditions. Structural and morphological features of the
      samples are investigated by X-ray diffraction, Raman spectroscopy, Scanning
      Electron Microscope (SEM), Transmission Electron Microscope (TEM) and UVVis
      spectrometer. Single phase zinc blende structure of as-synthesized undoped and
      doped-ZnS is confirmed by XRD and revealed by Rietveld fitting. SEM and TEM
      images show ultrafine nanoparticles having size in the range of 2 to 5nm. UV-Vis
      absorption spectra exhibit blue shift in absorption edge of undoped and doped ZnS
      as compared to bulk counterpart. The photocatalytic activity as a function of
      dopant concentration and irradiation time is systematically studied. The rate of
      de-coloration of dyes is detected by UVVis absorption spectroscopy and organic
      dye mineralization is confirmed by table of carbon (TOC) study. The
      photocatalytic activity of Mn-doped ZnS is highest amongst all dopants; however
      Co as a dopant is found to reduce photocatalytic activity than pure ZnS. 

PMID- 27037761
TI  - Association Between Oral Health and Cognitive Status: A Systematic Review.
AB  - OBJECTIVES: To systematically review longitudinal studies examining the
      association between oral health and cognitive decline. DESIGN: Studies published
      between January 1993 and March 2013 were identified by search of English language
      publications in PubMed/Medline using relevant Medical Subject Heading terms and
      title and abstract keywords and from CINAHL using relevant subject headings.
      After applying eligibility criteria and adding four studies identified from
      article references, 56 of the 1,412 articles identified remained; 40 were cross
      sectional, and 16 were longitudinal; 11 of the latter examined the effect of oral
      health on change in cognitive health or dementia incidence, five examined the
      reverse. SETTING: Sources of information included administrative data, subject
      evaluations in parent studies, medical and dental records, self-reports, and in
      person evaluations. PARTICIPANTS: Older adults. MEASUREMENTS: Most studies used
      subjects whose oral or cognitive status was known, using standard approaches to
      impute for missing information. The oral health information most frequently
      studied included number of teeth, periodontal and caries problems, and denture
      use. Cognition was most frequently evaluated using the Mini-Mental State
      Examination or according to a diagnosis of dementia. RESULTS: Some studies found
      that oral health measures such as number of teeth and periodontal disease were
      associated with risk of cognitive decline or incident dementia, whereas others
      did not find an association. Similarly, cognitive decline was not consistently
      associated with greater loss of teeth or number of decayed teeth. It is likely
      that methodological limitations play a major role in explaining the inconsistent
      findings. CONCLUSION: It is unclear how or whether oral health and cognitive
      status are related. Additional research is needed in which there is greater
      agreement on how oral health and cognitive states are assessed to better examine
      the linkages between these two health outcomes.

PMID- 27037763
TI  - Comments on "Synthesis aspects, structural, spectroscopic, antimicrobial and room
      temperature ferromagnetism of zinc iodide complex with Schiff based ligand" by K.
      Shakila and S. Kalainathan, Spectrochim. Acta 135 A (2015) 1059-1065.
AB  - Shakila and Kalainathan report on the synthetic and structural aspects of a zinc
      iodide complex with Schiff based ligand, which exhibits room temperature
      ferromagnetism. In this comment, many points of criticism, concerning the
      characterization of this so called zinc iodide complex of Schiff based ligand are
      highlighted to prove that the title paper is completely erroneous. 

PMID- 27037764
TI  - Advanced glycation end products induce differential structural modifications and
      fibrillation of albumin.
AB  - Glycation induced amyloid fibrillation is fundamental to the development of many
      neurodegenerative and cardiovascular complications. Excessive non-enzymatic
      glycation in conditions such as hyperglycaemia results in the increased
      accumulation of advanced glycation end products (AGEs). AGEs are highly reactive
      pro-oxidants, which can lead to the activation of inflammatory pathways and
      development of oxidative stress. Recently, the effect of non-enzymatic glycation
      on protein structure has been the major research area, but the role of specific
      AGEs in such structural alteration and induction of fibrillation remains
      undefined. In this study, we determined the specific AGEs mediated structural
      modifications in albumin mainly considering carboxymethyllysine (CML),
      carboxyethyllysine (CEL), and argpyrimidine (Arg-P) which are the major AGEs
      formed in the body. We studied the secondary structural changes based on circular
      dichroism (CD) and spectroscopic analysis. The AGEs induced fibrillation was
      determined by Congo red binding and examination of scanning and transmission
      electron micrographs. The amyloidogenic regions in the sequence of BSA were
      determined using FoldAmyloid. It was observed that CEL modification of BSA leads
      to the development of fibrillar structures, which was evident from both secondary
      structure changes and TEM analysis. 

PMID- 27037765
TI  - SERS spectrum of gallic acid obtained from a modified silver colloid.
AB  - Two different crystals of the gallic acid were microscopically separated from a
      p.a. commercial product. The Raman spectra analysis allowed distinguishing
      monomeric and dimeric structures. The vibrational wave numbers were computed
      using DFT quantum chemical calculations. The data obtained from wave number
      calculations are used to assign vibrational bands obtained in the Raman spectrum.
      The dimer, characterized as ellagic acid, involves the carboxyl and hydroxyl
      moieties. The Raman spectrum in water solution of each species is dominated by
      the monomeric form. A low negatively charged Ag colloid allowed obtain to the
      best of our knowledge, the first surface enhanced Raman scattering (SERS)
      spectrum of the gallic acid. The possible electrophilic attacking sites of the
      title molecule are identified using MEP surface plot study and the orientation of
      the analyte on the metal surface is proposed tilted to the surface. 

PMID- 27037766
TI  - Invited review: Architectures and mechanisms of ATP binding cassette proteins.
AB  - ATP binding cassette (ABC) ATPases form chemo-mechanical engines and switches
      that function in a broad range of biological processes. Most prominently, a very
      large family of integral membrane NTPases-ABC transporters-catalyzes the import
      or export of a diverse molecules across membranes. ABC proteins are also
      important components of the chromosome segregation, recombination, and DNA repair
      machineries and regulate or catalyze critical steps of ribosomal protein
      synthesis. Recent structural and mechanistic studies draw interesting
      architectural and mechanistic parallels between diverse ABC proteins. Here, I
      review this state of our understanding how NTP-dependent conformational changes
      of ABC proteins drive diverse biological processes. (c) 2016 Wiley Periodicals,
      Inc. Biopolymers 105: 492-504, 2016. 

PMID- 27037768
TI  - Evaluation of the detoxication efficiencies for acrylonitrile wastewater treated
      by a combined anaerobic oxic-aerobic biological fluidized tank (A/O-ABFT)
      process: Acute toxicity and zebrafish embryo toxicity.
AB  - Acrylonitrile (ACN) wastewater generated during ACN production has been reported
      to be toxic to many aquatic organisms. However, few studies have evaluated
      toxicity removal of ACN wastewater during and after the treatment process. In
      this study, the detoxication ability of an ACN wastewater treatment plant (WWTP)
      was evaluated using Daphnia magna, Danio rerio and zebrafish embryo. This ACN
      WWTP has a combined anaerobic oxic-aerobic biological fluidized tank (A/O-ABFT)
      process upgraded from the traditional anaerobic oxic (A/O) process. Moreover, the
      potential toxicants of the ACN wastewaters were identified by gas chromatography
      mass spectrometry (GC-MS). The raw ACN wastewater showed high acute and embryo
      toxicity. 3-Cyanopyridine, succinonitrile and a series of nitriles were detected
      as the toxic contributors of ACN wastewater. The A/O process was effective for
      the acute and embryo toxicity removal, as well as the organic toxicants. However,
      the A/O effluent still showed acute and embryo toxicity which was attributed by
      the undegraded and the newly generated toxicants during the A/O process. The
      residual acute and embryo toxicity as well as the organic toxicants in the A/O
      effluent were further reduced after going through the downstream ABFT process
      system. The final effluent displayed no significant acute and embryo toxicity,
      and less organic toxicants were detected in the final effluent. The upgrade of
      this ACN WWTP results in the improved removal efficiencies for acute and embryo
      toxicity, as well as the organic toxicants. 

PMID- 27037767
TI  - Atheroprotective effects of conjugated linoleic acid.
AB  - Atherosclerosis, the underlying cause of heart attack and strokes, is a
      progressive dyslipidaemic and inflammatory disease where monocyte-derived
      macrophage cells play a pivotal role. Although most of the mechanisms that
      contribute to the progression of atherosclerosis have been identified, there is
      limited information on those governing regression. Conjugated linoleic acid (CLA)
      is a generic term denoting a group of naturally occurring isomers of linoleic
      acid (18:2, n6) that differ in the position or geometry (i.e. cis or trans) of
      their double bonds. The most predominant isomers in ruminant fats are cis-9,
      trans-11 CLA (c9,t11-CLA), which accounts for more than 80% of CLA isomers in
      dairy products and trans-10, cis-12 CLA (t10,c12-CLA). Dietary administration of
      a blend of the two most abundant isomers of CLA has been shown to inhibit the
      progression and induce the regression of pre-established atherosclerosis. Studies
      investigating the mechanisms involved in CLA-induced atheroprotective effects are
      continually emerging. The purpose of this review is to discuss comprehensively
      the effects of CLA on monocyte/macrophage function in atherosclerosis and to
      identify possible mechanisms through which CLA mediates its atheroprotective
      effects.

PMID- 27037769
TI  - Introducing sequential managed aquifer recharge technology (SMART) - From
      laboratory to full-scale application.
AB  - Previous lab-scale studies demonstrated that stimulating the indigenous soil
      microbial community of groundwater recharge systems by manipulating the
      availability of biodegradable organic carbon (BDOC) and establishing sequential
      redox conditions in the subsurface resulted in enhanced removal of compounds with
      redox-dependent removal behavior such as trace organic chemicals. The aim of this
      study is to advance this concept from laboratory to full-scale application by
      introducing sequential managed aquifer recharge technology (SMART). To validate
      the concept of SMART, a full-scale managed aquifer recharge (MAR) facility in
      Colorado was studied for three years that featured the proposed sequential
      configuration: A short riverbank filtration passage followed by subsequent re
      aeration and artificial recharge and recovery. Our findings demonstrate that
      sequential subsurface treatment zones characterized by carbon-rich (>3 mg/L BDOC)
      to carbon-depleted (<=1 mg/L BDOC) and predominant oxic redox conditions can be
      established at full-scale MAR facilities adopting the SMART concept. The
      sequential configuration resulted in substantially improved trace organic
      chemical removal (i.e. higher biodegradation rate coefficients) for moderately
      biodegradable compounds compared to conventional MAR systems with extended travel
      times in an anoxic aquifer. Furthermore, sorption batch experiments with clay
      materials dispersed in the subsurface implied that sorptive processes might also
      play a role in the attenuation and retardation of chlorinated flame retardants
      during MAR. Hence, understanding key factors controlling trace organic chemical
      removal performance during SMART allows for systems to be engineered for optimal
      efficiency, resulting in improved removal of constituents at shorter subsurface
      travel times and a potentially reduced physical footprint of MAR installations. 

PMID- 27037770
TI  - Insights into reptile dermal contaminant exposure: Reptile skin permeability to
      pesticides.
AB  - There is growing interest in improving ecological risk assessment exposure
      estimation, specifically by incorporating dermal exposure. At the same time,
      there is a growing interest in amphibians and reptiles as receptors in ecological
      risk assessment, despite generally receiving less research than more traditional
      receptors. Previous research has suggested that dermal exposure may be more
      important than previously considered for reptiles. We measured reptile skin
      permeability to four pesticides (thiamethoxam, malathion, tebuthiuron,
      trifluralin) using ventral skin samples. All four pesticides penetrated the skin
      but generally had low permeability. There was no apparent relationship between
      physicochemical properties and permeability coefficients. Malathion had a
      significantly greater permeability rate at all time points compared to the other
      pesticides. Tebuthiuron had a greater permeability than thiamethoxam. Reptiles
      and mammals appear to have similar skin permeability suggesting that dermal
      exposure estimates for mammals may be representative of reptiles. 

PMID- 27037771
TI  - A QSAR for the prediction of rate constants for the reaction of VOCs with nitrate
      radicals.
AB  - A QSAR for the prediction of rate constants for the degradation of volatile
      organic compounds by nitrate radicals is developed using the Partial Least
      Squares technique. The QSAR is based on experimental data published in the
      literature for 260 compounds. They are modeled by a set of calculated descriptors
      from standard descriptor generation tools and from quantum chemistry. Out of
      several diversity-based partitionings of the data set a diverse set of 99
      compounds turned out to be the optimum choice with regard to simplicity and
      performance. The final QSAR model is characterized by r(2) = 0.831 (fit) and q(2)
      = 0.823 (prediction), and by an r(2)pred = 0.862 for the n = 155 external
      validation set. The QSAR needs 3 latent variables. The most important descriptors
      for the QSAR are the ionization potential, obtained from density functional
      theory, and the energy of the highest occupied molecular orbital, which are
      modulated by fingerprints indicating the presence of specific molecular fragments
      like functional groups or ring systems. The applicability domain of the new QSAR
      was studied for some compound classes which are important for the crop protection
      industry, including (di)hydroxbenzenes and heterocyclic compounds. 

PMID- 27037772
TI  - Predicting changes in aquatic toxicity of chemicals resulting from solvent or
      dispersant use as vehicle.
AB  - The influence of two vehicles (N,N-dimethylformamide [DMF] as solvent and
      polyoxyethylene hydrogenated castor oil [HCO-40] as a dispersant) on the acute
      toxicity of eight hydrophobic chemicals with a non-specific mode of action to
      Daphnia magna was investigated according to the OECD Guidelines for the Testing
      of Chemicals, No. 202. An increased 48-h EC50 value for D. magna or reduced
      toxicity resulting from the addition of HCO-40 to the test medium was observed
      for five of the eight chemicals examined. Each of eight chemicals was dissolved
      in water at a concentration of either 10 mg/L or 1.0 mg/L, with or without DMF or
      HCO-40. Silicone film as a model of a biological membrane was then immersed in
      each solution, and the concentration of each chemical in the water was monitored
      until equilibrium was reached for each test substance, after which the adsorbed
      amount of each chemical was determined. The amounts of p-pentylphenol and four
      other substances with log Pow (1-octanol/water partition coefficient) values
      greater than 3.4 adsorbed onto the silicone film decreased with increasing
      concentrations of HCO-40. However, 3-chloro-4-fluoronitrobenzene and two other
      substances with log Pow values less than 2.6 demonstrated no changes in
      adsorption with either increasing HCO-40 concentration or the addition of DMF.
      The reduced adsorption in the presence of a vehicle on the silicone film
      correlated closely with changes in toxicity. These results indicate that the
      methodology developed in this study enables the prediction of changes in toxicity
      resulting from the addition of vehicles to a test system. 

PMID- 27037773
TI  - Tracing changes in atmospheric sources of lead contamination using lead isotopic
      compositions in Australian red wine.
AB  - Air quality data detailing changes to atmospheric composition from Australia's
      leaded petrol consumption is spatially and temporally limited. In order to
      address this data gap, wine was investigated as a potential proxy for atmospheric
      lead conditions. Wine spanning sixty years was collected from two wine regions
      proximal to the South Australian capital city, Adelaide, and analysed for lead
      concentration and lead and strontium isotopic composition for source
      apportionment. Maximum wine lead concentrations (328 MUg/L) occur prior to the
      lead-in-air monitoring in South Australia in the later 1970s. Wine lead
      concentrations mirror available lead-in-air measurements and show a declining
      trend reflecting parallel reductions in leaded petrol emissions. Lead from petrol
      dominated the lead in wine ((206)Pb/(207)Pb: 1.086; (208)Pb/(207)Pb: 2.360) until
      the introduction of unleaded petrol, which resulted in a shift in the wine lead
      isotopic composition closer to vineyard soil ((206)Pb/(207)Pb: 1.137;
      (208)Pb/(207)Pb: 2.421). Current mining activities or vinification processes
      appear to have no impact with recent wine samples containing less than 4 MUg/L of
      lead. This study demonstrates wine can be used to chronicle changes in
      environmental lead emissions and is an effective proxy for atmospherically
      sourced depositions of lead in the absence of air quality data. 

PMID- 27037774
TI  - Nodules behind the ears: IgG4-related skin disease.
AB  - A 53-year-old healthy factory worker consulted our hospital complaining of small
      nodules of similar size, shape and location on both ears. The nodules revealed
      focal and massive infiltration of lymphocytes, plasma cells and eosinophils with
      fibrosis. They had no specific structure on pathological staining with
      haematoxylin and eosin. Immunostaining for IgG4 revealed that a large majority of
      the IgG+ cells were positive for IgG4. The ratio of IgG4+ to IgG+ plasma cells
      was approximately 40%. IgG4+ plasma cells were present at approximately 250 per
      high-power field. The patient was diagnosed with IgG4-related skin disease
      without multiple organ involvement in the systemic syndrome of IgG4-related
      diseases. Because the patient was a factory worker and exposed to an environment
      of metallic dust, a skin patch test that included a metal series was performed.
      Zinc and manganese produced positive reactions. Because only skin lesions were
      observed in this case, not multiple organ involvement, tissue infiltration by
      IgG4+ plasma cells might have resulted from continuous sensitization to zinc
      and/or manganese.

PMID- 27037775
TI  - SRC Family Kinase Inhibition in Ewing Sarcoma Cells Induces p38 MAP Kinase
      Mediated Cytotoxicity and Reduces Cell Migration.
AB  - Ewing sarcoma (ES) is a highly aggressive bone and soft tissue cancer,
      representing the second most common primary malignant bone tumor in children and
      adolescents. Although the development of a multimodal therapy, including both
      local control (surgery and/or radiation) and systemic multidrug chemotherapy, has
      determined a significant improvement in survival, patients with metastatic and
      recurrent disease still face a poor prognosis. Moreover, considering that ES
      primarily affects young patients, there are concerns about long-term adverse
      effects of the therapy. Therefore, more rational strategies, targeting specific
      molecular alterations underlying ES, are required. Recent studies suggest that
      SRC family kinases (SFKs), which are aberrantly activated in most cancer types,
      could represent key therapeutic targets also for ES. Here, we challenged ES cell
      lines with a recently developed selective SFK inhibitor (a pyrazolo[3,4
      d]pyrimidine derivative, called SI221), which was previously shown to be a
      valuable proapoptotic agent in other tumor types while not affecting normal
      cells. We observed that SI221 significantly reduced ES cell viability and proved
      to be more effective than the well-known SFK inhibitor PP2. SI221 was able to
      induce apoptosis in ES cells and also reduced ES cell clonogenic potential.
      Furthermore, SI221 was also able to reduce ES cell migration. At the molecular
      level, our data suggest that SFK inhibition through SI221 could reduce ES cell
      viability at least in part by hindering an SFK-NOTCH1 receptor-p38 mitogen
      activated protein kinase (MAPK) axis. Overall, our study suggests a potential
      application of specific SFK inhibition in ES therapy. J. Cell. Physiol. 232: 129
      135, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037776
TI  - Prenatal exposure to environmental phenols and childhood fat mass in the Mount
      Sinai Children's Environmental Health Study.
AB  - Early life exposure to endocrine disrupting chemicals may alter adipogenesis and
      energy balance leading to changes in obesity risk. Several studies have evaluated
      the association of prenatal bisphenol A exposure with childhood body size but
      only one study of male infants has examined other environmental phenols.
      Therefore, we assessed associations between prenatal exposure to environmental
      phenols and fat mass in a prospective birth cohort. We quantified four phenol
      biomarkers in third trimester maternal spot urine samples in a cohort of women
      enrolled in New York City between 1998 and 2002 and evaluated fat mass in their
      children using a Tanita scale between ages 4 and 9years (173 children with 351
      total observations). We estimated associations of standard deviation differences
      in natural log creatinine-standardized phenol biomarker concentrations with
      percent fat mass using linear mixed effects regression models. We did not observe
      associations of bisphenol A or triclosan with childhood percent fat mass. In
      unadjusted models, maternal urinary concentrations of 2,5-dichlorophenol were
      associated with greater percent fat mass and benzophenone-3 was associated with
      lower percent fat mass among children. After adjustment, phenol biomarkers were
      not associated with percent fat mass. However, the association between
      benzophenone-3 and percent fat mass was modified by child's sex: benzophenone-3
      concentrations were inversely associated with percent fat mass in girls (beta=
      1.51, 95% CI=-3.06, 0.01) but not boys (beta=-0.20, 95% CI=-1.69, 1.26). Although
      we did not observe strong evidence that prenatal environmental phenols exposures
      influence the development of childhood adiposity, the potential antiadipogenic
      effect of benzophenone-3 in girls may warrant further investigation. 

PMID- 27037777
TI  - Stimuli-responsive lipid nanotubes in gel formulations for the delivery of
      doxorubicin.
AB  - Lipid nanotubes (LNTs) are one of the most advantageous structures for drug
      delivery and targeting. LNTs formed by a specially designed molecule called AQUA
      (AQ-NH-(CH2)10COOH (AQ: anthraquinone group) is used for drug delivery, and
      doxorubicin (DOX) is the drug selected. DOX and AQUA have some similarities in
      their molecular structures, so a significant amount of DOX can be loaded to LNTs.
      The AQUA LNTs are pH responsive, and drug loading increased almost linearly by
      increasing the pH, reaching a maximum value (96%) at pH 9.0. In terms of drug
      release, lower pHs are preferred. Drug-loaded LNTs are also mixed with four
      different gels (chitosan, alginate, hydroxypropyl methylcellulose and
      polycarbophil) to use the advantages of these gels. The drug release efficiency
      is studied using a Franz diffusion cell in which sheep colon membranes and
      dialysis membranes are utilized. The amount of released DOX from the chitosan gel
      formulations was quite high. Sodium alginate gels had lower release and slower
      diffusion of DOX. The cytotoxic effect of DOX-loaded AQUA LNTs has also been
      determined on cell cultures. Our new lipid nanotubes are a non-toxic, effective,
      biodegradable, biocompatible, stable and promising system for drug delivery and
      can be used for colonic administration of DOX for the treatment of colorectal
      cancer (CRC). 

PMID- 27037778
TI  - Electrospun tilapia collagen nanofibers accelerating wound healing via inducing
      keratinocytes proliferation and differentiation.
AB  - The development of biomaterials with the ability to induce skin wound healing is
      a great challenge in biomedicine. In this study, tilapia skin collagen sponge and
      electrospun nanofibers were developed for wound dressing. The collagen sponge was
      composed of at least two alpha-peptides. It did not change the number of spleen
      derived lymphocytes in BALB/c mice, the ratio of CD4(+)/CD8(+) lymphocytes, and
      the level of IgG or IgM in Sprague-Dawley rats. The tensile strength and contact
      angle of collagen nanofibers were 6.72+/-0.44MPa and 26.71+/-4.88 degrees ,
      respectively. They also had good thermal stability and swelling property.
      Furthermore, the nanofibers could significantly promote the proliferation of
      human keratinocytes (HaCaTs) and stimulate epidermal differentiation through the
      up-regulated gene expression of involucrin, filaggrin, and type I
      transglutaminase in HaCaTs. The collagen nanofibers could also facilitate rat
      skin regeneration. In the present study, electrospun biomimetic tilapia skin
      collagen nanofibers were succesfully prepared, were proved to have good
      bioactivity and could accelerate rat wound healing rapidly and effectively. These
      biological effects might be attributed to the biomimic extracellular matrix
      structure and the multiple amino acids of the collagen nanofibers. Therefore, the
      cost-efficient tilapia collagen nanofibers could be used as novel wound dressing,
      meanwhile effectively avoiding the risk of transmitting animal disease in the
      future clinical apllication. 

PMID- 27037779
TI  - Polycaprolactone-laponite composite scaffold releasing strontium ranelate for
      bone tissue engineering applications.
AB  - We report polycaprolactone-laponite composite scaffold for the controlled release
      of strontium ranelate (SRA), a drug for osteoporosis. Laponite-SRA complex with
      electrostatic interaction between the drug and laponite was obtained through an
      aqueous phase reaction. Structural evaluation verified complexation of the bulky
      SRA molecules with the negatively charged laponite tactoid surfaces, leading to
      extended ordering of the tactoids, leaving behind the interlayer spacing of the
      laponite unchanged. The laponite-SRA complex was solution blended with
      polycaprolactone to obtain composite scaffolds. The strategy was found improving
      the dispersibility of laponite in PCL due to partial organomodification imparted
      through interaction with the SRA. The composite scaffolds with varying laponite
      SRA complex content of 3-12wt% were evaluated in vitro using human osteosarcoma
      cells. It was confirmed that an optimum composition of the scaffold with 3wt%
      laponite-SRA complex loading would be ideal for obtaining enhanced ALP activity,
      by maintaining cell viability. 

PMID- 27037780
TI  - Potential of non-mulberry silk protein fibroin blended and grafted poly(?
      caprolactone) nanofibrous matrices for in vivo bone regeneration.
AB  - An in vivo investigation is conducted to evaluate effectiveness of poly(?
      caprolactone) (PCL) nanofibrous matrices, with non-mulberry silk fibroin (NSF)
      (from Antheraea mylitta) inclusion, for bone tissue engineering. Inclusion is
      achieved by either blending NSF with PCL prior to electrospinning substrates or
      by grafting NSF onto electrospun PCL substrates. Proceeding from our previous in
      vitro results, showing that NSF grafted matrices have an edge when it comes to
      aiding cellular adhesion and proliferation, animal trials using rabbits are
      planned. As this is first in vivo trial of nanofibrous scaffolds with silk
      fibroin from A. mylitta, aim is to both evaluate the grafted and blended
      scaffolds independently and compare the method of silk fibroin introduction into
      the nanofibrous structures. The scaffolds are implanted at bone defect site in
      distal metaphysis region of the rabbits' femur. Host tissue immuno-compatibility
      of implants is assessed from measurements of IL-2, IL-6 and TNF-alpha level
      through 4 weeks after implantation. Barring an initial inflammatory response, IL
      2, IL-6 and TNF-alpha levels fall back at baseline values in 2 or 4 weeks, thus
      confirming long term compatibility. Substantial interfacial bonding strength
      between grafts and host bone is evidenced from mechanical push-out test.
      Formation of bone tissue for both implant varieties is confirmed using
      histological and radiological examinations along with fluorochrome labelling and
      scanning electron microscopy. Significantly better bone formation is observed for
      NSF grafted matrices. The cumulative results from in vivo tests indicate
      suitability of NSF grafted PCL nanofibrous matrix as an ECM for bone repair and
      regrowth. 

PMID- 27037781
TI  - Aggregation-induced emissive nanoparticles for fluorescence signaling in a low
      cost paper-based immunoassay.
AB  - Low cost paper based immunoassays are receiving interest due to their fast
      performance and small amounts of biomolecules needed for developing an
      immunoassay complex. In this work aggregation-induced emissive (AIE)
      nanoparticles, obtained from a diastereoisomeric mixture of 1,2-di-(4
      hydroxyphenyl)-1,2-diphenylethene (TPEDH) in a one-step top-down method, are
      characterized through Dynamic Light Scattering (DLS), Scanning Electron
      Microscopy (SEM), and Zeta potential. By measuring the Zeta potential before and
      after labeling the nanoparticles with antibodies we demonstrate that the
      colloidal system is stable in a wide pH-range. The AIE-active nanoparticles are
      deposited on chitosan and glutaraldehyde modified paper pads overcoming the
      common aggregation-caused quenching (ACQ) effect. Analyte concentrations from
      1000ng and below are applied in a model immunocomplex using Goat anti-Rabbit IgG
      and Rabbit IgG. In the range of 7.81ng-250ng, linear trends with a high R(2) are
      observed, which leads to a strong increase of the blue fluorescence from the
      TPEDH nanoparticles. 

PMID- 27037782
TI  - Nanoporous anodic titanium dioxide layers as potential drug delivery systems:
      Drug release kinetics and mechanism.
AB  - Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a
      three step anodization process in an electrolyte based on an ethylene glycol
      solution with fluoride ions. Some of the ATO samples were heat-treated in order
      to achieve two different crystallographic structures - anatase (400 degrees C)
      and a mixture of anatase and rutile (600 degrees C). The structural and
      morphological characterizations of ATO layers were performed using a field
      emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was
      determined with contact angle measurements using distilled water. Ibuprofen and
      gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in
      vitro drug release was conducted for 24h under a static and dynamic flow
      conditions in a phosphate buffer solution at 37 degrees C. The drug
      concentrations were determined using UV-Vis spectrophotometry. The absorbance of
      ibuprofen was measured directly at 222nm, whether gentamicin was determined as a
      complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited
      long term release profiles, despite the ATO structure. A new release model, based
      on the desorption of the drug from the ATO top surface followed by the desorption
      and diffusion of the drug from the nanopores, was derived. The proposed release
      model was fitted to the experimental drug release profiles, and kinetic
      parameters were calculated. 

PMID- 27037783
TI  - The potential use of novel chitosan-coated deformable liposomes in an ocular drug
      delivery system.
AB  - In this study, novel chitosan-coated deformable liposomes (DL-CS) were proposed
      as an ocular drug delivery system to prolong pre-corneal retention, and improve
      transcorneal penetration and absorption. Flurbiprofen-loaded deformable liposomes
      (FP-DL) were prepared by a modified ethanol injection method and then coated with
      chitosan. Both DL and DL-CS exhibited a homogeneous particle size distribution,
      high encapsulation efficiency and good stability. After coating with 0.1% CS, the
      zeta potential was shifted from negative to positive. The apparent permeability
      coefficient of FP-DL-0.1% CS evaluated using isolated rabbit corneas was 1.29-,
      1.95- and 4.59- fold greater than that of uncoated FP-DL, conventional liposomes
      and FP solution (P<0.01), respectively. The in vivo pre-corneal retention time
      and elimination dynamics were assessed using gamma scintigraphy technology. The
      area under the remaining activity-time of FP-DL-0.1% CS was prolonged 2.84- and
      1.53-fold compared with that of the FP solution and FP-DL groups, respectively.
      Moreover, the ocular irritation test in vivo revealed that DL-0.1% CS produced no
      ocular damage or abnormal clinical signs. These results indicate that DL-CS
      appears to be a novel ophthalmic drug delivery strategy with the potential to
      overcome the limitations of conventional eye drops. 

PMID- 27037784
TI  - Pegylated polyelectrolyte nanoparticles containing paclitaxel as a promising
      candidate for drug carriers for passive targeting.
AB  - Targeted drug delivery systems are of special importance in cancer therapies,
      since serious side effects resulting from unspecific accumulation of highly toxic
      chemotherapeutics in healthy tissues can restrict effectiveness of the therapy.
      In this work we present the method of preparing biocompatible, polyelectrolyte
      nanoparticles containing the anticancer drug that may serve as a vehicle for
      passive tumor targeting. The nanoparticles were prepared via direct encapsulation
      of emulsion droplets in a polyelectrolyte multilayer shell. The oil cores that
      contained paclitaxel were stabilized by docusate sodium salt/poly-l-lysine
      surface complex (AOT/PLL) and were encapsulated in shells formed by the LbL
      adsorption of biocompatible polyelectrolytes, poly-L-glutamic acid (PGA) and PLL
      up to 5 or 6 layers. The surface of the nanoparticles was pegylated through the
      adsorption of the pegylated polyelectrolyte (PGA-g-PEG) as the outer layer to
      prolong the persistence of the nanocarriers in the circulation. The synthesized
      nanoparticles were stable in cell culture medium containing serum and their
      average size was 100nm, which makes them promising candidates for passive
      targeted drug delivery. This notion was further confirmed by the results of
      studying the biological effects of nanoformulations on two tumor cell lines:
      mouse colon carcinoma cell line CT26-CEA and the mouse mammary carcinoma cell
      line 4T1. The empty polyelectrolyte nanoparticles did not affect the viability of
      the tested cells, whereas encapsulated paclitaxel retained its strong
      cytotoxic/cytostatic activity. 

PMID- 27037785
TI  - Biosurfactant templated quantum sized fluorescent gold nanoclusters for in vivo
      bioimaging in zebrafish embryos.
AB  - We report the biosurfactant (sodium cholate) templated bright bluish-green
      emitting gold nanoclusters (AuNCs) by green chemical approach. Optical properties
      of the AuNCs were studied using UV-vis and luminescence spectroscopy. Lifetime of
      the fluorescent AuNCs was measured using time correlated single photon counting
      technique (TCSPC). High-resolution transmission electron microscopy (HR-TEM) and
      dynamic light scattering (DLS) were used to measure the sizes of the clusters. In
      vivo toxicity and bioimaging studies of sodium cholate (NaC) templated AuNCs were
      carried out at different developmental stages of zebrafish embryos. The survival
      rate, hatching rate, heart rate, malformation and apoptotic gene expression
      experiments shows no significant toxicity in developing embryos up to 100MUL/mL
      of AuNCs concentration and the AuNCs stained embryos exhibited green fluorescence
      with high intensity over the period from 4 to 96hpf (hours post fertilization)
      which shows that AuNCs were stable in living organisms. 

PMID- 27037786
TI  - Restructuring reward processing with Mindfulness-Oriented Recovery Enhancement:
      novel therapeutic mechanisms to remediate hedonic dysregulation in addiction,
      stress, and pain.
AB  - Though valuation processes are fundamental to survival of the human species,
      hedonic dysregulation is at the root of an array of maladies, including
      addiction, stress, and chronic pain, as evidenced by the allostatic shift in the
      relative salience of natural reward to drug reward observed among persons with
      severe substance use disorders. To address this crucial problem, novel
      interventions are needed to restore hedonic regulatory processes gone awry in
      persons exhibiting addictive behaviors. This article describes a theoretical
      rationale and empirical evidence for the effects of one such new intervention,
      Mindfulness-Oriented Recovery Enhancement (MORE), on top-down and bottom-up
      mechanisms implicated in cognitive control and hedonic regulation. MORE is
      innovative and distinct from extant mindfulness-based interventions in that it
      unites traditional mindfulness meditation with reappraisal and savoring
      strategies designed to reverse the downward shift in salience of natural reward
      relative to drug reward, representing a crucial tipping point to disrupt the
      progression of addiction-a mechanistic target that no other behavioral
      intervention has been designed to address. Though additional studies are needed,
      clinical and biobehavioral data from several completed and ongoing trials suggest
      that MORE may exert salutary effects on addictive behaviors and the
      neurobiological processes that underpin them.

PMID- 27037787
TI  - Adverse effects of incretin-based therapies on major cardiovascular and
      arrhythmia events: meta-analysis of randomized trials.
AB  - BACKGROUND: Recent cardiovascular outcome trials of incretin-based therapies
      (IBT) in type 2 diabetes have not demonstrated either benefit or harm in terms of
      major adverse cardiovascular events (MACE). Earlier meta-analyses showed
      conflicting results but were limited in methodology. We aimed to perform an
      updated meta-analysis of all available incretin therapies on the incidence of
      MACE plus arrhythmia and heart failure. METHODS: We identified studies published
      through November 2014 by searching electronic databases and reference lists. We
      included RCTs in which the intervention group received incretin-based therapies
      and the control group received placebo or standard treatment; enrolled >100
      participants in each group; interventions lasted >24 weeks; and reported data on
      one or more primary major adverse cardiovascular events endpoints plus terms for
      arrhythmia and heart failure. We used the Peto method for each CV event for
      individual IBT treatment. RESULTS: In this meta-analysis of 100 RCTs involving
      54,758 incretin-based therapies users and 48,175 controls, exenatide was
      associated with increased risk of arrhythmia (OR 2.83; 95% CI, 1.06-7.57);
      saxagliptin was associated with an increased risk of heart failure (OR 1.23; 95%
      CI, 1.03-1.46), and sitagliptin was associated with a significantly decreased
      risk of all cause death compared to active controls (OR 0.39, 95% CI 0.18-0.82).
      CONCLUSIONS: In type 2 diabetes, exenatide may increase the risk of arrhythmia,
      and sitagliptin may reduce the risk of all cause death; however, the subgroup of
      patients most likely to experience harm or benefit is unclear. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27037788
TI  - Vitamin D insufficiency and cognitive impairment in Asians: a multi-ethnic
      population-based study and meta-analysis.
AB  - BACKGROUND: The relationship between vitamin D insufficiency and cognitive
      impairment remains equivocal in Asians. We examined the association between
      circulating 25-hydroxyvitamin D (25OHD) concentration and cognitive performance
      in a large multi-ethnic Singaporean population-based study. We also conducted a
      meta-analysis of 25OHD concentrations amongst cognitively impaired older adults
      in Asia. METHODS: Our population-based cross-sectional study included 2273
      persons >=60 years of age from the Singapore Epidemiology of Eye Diseases (SEED)
      study (mean +/- SD age 70.4 +/- 6.2 years; 44.7% female), who were categorized
      according to 25OHD concentration (i.e. <=10, 10.1-20 and >20 ng mL(-1) ). The
      25OHD concentration was measured and adjusted to reflect a deseasonalized value.
      Cognition was assessed using the total and domain scores of the Abbreviated
      Mental Test (AMT). Global cognitive impairment was defined as AMT score of <=6 if
      0-6 years of education and AMT score of <=8 if >7 years of education. Fully
      adjusted multivariate models were used. We included seven studies in a meta
      analysis of 25OHD and cognition in Asia (6068 participants; 1179 cognitively
      impaired cases). RESULTS: Participants with 25OHD levels >20 ng mL(-1) (n = 1302)
      had higher AMT total scores (mean +/- SD 8.5 +/- 1.9) and were less likely to
      have cognitive impairment (14.1%) than participants with lower 25OHD levels
      (overall P < 0.001, P-trend < 0.001). Deseasonalized 25OHD concentration was
      associated with AMT score (beta = 0.10 per 10 ng mL(-1) , P = 0.035). Vitamin D
      insufficiency (25OHD <=20 ng mL(-1) ) was associated with global cognitive
      impairment (OR 1.56, P = 0.028). Specifically, 25OHD concentration correlated
      with semantic memory (r = 0.08, P = 0.009) and orientation in time (r = 0.09, P =
      0.003). In the meta-analysis, the pooled mean 25OHD difference was -6.83 ng mL(
      1) (95% confidence interval -11.36; -2.30), indicating lower 25OHD concentrations
      amongst cognitively impaired compared to cognitively healthy participants in
      Asia. CONCLUSION: Vitamin D insufficiency is associated with a greater likelihood
      of and more severe cognitive impairment in Asian populations.

PMID- 27037789
TI  - Mono- and Ditopic Bisfunctionalization of Graphene.
AB  - For the first time, the bisfunctionalization of graphene by employing two
      successive reduction and covalent bond forming steps is reported. Bulk
      functionalization in dispersion and functionalization of individual sheets
      deposited on surfaces have both been carried out. Whereas in the former case
      attacks from both sides of the basal plane are possible and can lead to strain
      free architectures, in the latter case, retrofunctionalizations can become
      important when the corresponding anion of the addend is a sufficiently good
      leaving group.

PMID- 27037790
TI  - Arctic marine phytobenthos of northern Baffin Island.
AB  - Global climate change is expected to alter the polar bioregions faster than any
      other marine environment. This study assesses the biodiversity of seaweeds and
      associated eukaryotic pathogens of an established study site in northern Baffin
      Island (72 degrees  N), providing a baseline inventory for future work assessing
      impacts of the currently ongoing changes in the Arctic marine environment. A
      total of 33 Phaeophyceae, 24 Rhodophyceae, 2 Chlorophyceae, 12 Ulvophyceae, 1
      Trebouxiophyceae, and 1 Dinophyceae are reported, based on collections of an
      expedition to the area in 2009, complemented by unpublished records of Robert T.
      Wilce and the first-ever photographic documentation of the phytobenthos of the
      American Arctic. Molecular barcoding of isolates raised from incubated substratum
      samples revealed the presence of 20 species of brown seaweeds, including
      gametophytes of kelp and of a previously unsequenced Desmarestia closely related
      to D. viridis, two species of Pylaiella, the kelp endophyte Laminariocolax
      aecidioides and 11 previously unsequenced species of the Ectocarpales,
      highlighting the necessity to include molecular techniques for fully unraveling
      cryptic algal diversity. This study also includes the first records of Eurychasma
      dicksonii, a eukaryotic pathogen affecting seaweeds, from the American Arctic.
      Overall, this study provides both the most accurate inventory of seaweed
      diversity of the northern Baffin Island region to date and can be used as an
      important basis to understand diversity changes with climate change.

PMID- 27037791
TI  - Altered cerebellar-cerebral functional connectivity in benign adult familial
      myoclonic epilepsy.
AB  - OBJECTIVE: The pathogenesis of benign adult familial myoclonic epilepsy (BAFME)
      remains unknown, although cerebellar pathologic changes and brain
      hyperexcitability have been reported. We used resting-state functional magnetic
      resonance imaging (fMRI) to examine the functional connectivity between the
      cerebellum and cerebrum in a Chinese family with BAFME for the first time.
      METHODS: Eleven adults with BAFME and 15 matched healthy controls underwent
      resting-state blood oxygen level-dependent (BOLD) fMRI scanning. The cerebellar
      seeds, including the bilateral crus I, lobule VIII, lobule VIIb, and lobule IV&V,
      were defined a priori. Next, regional time courses were obtained for each
      individual by averaging the BOLD time series over all voxels in each seed region.
      Then, seed-based functional connectivity z-maps were produced by computing
      Pearson's correlation coefficients (converted to z-scores by Fisher
      transformation) between each seed signal and the time series from all other
      voxels within the entire brain. Finally, a second-level random-effect two-sample
      t-test was performed on the individual z-maps in a voxel-wise manner. RESULTS:
      Reduced functional connectivity of the right cerebellar crus I with the left
      middle frontal gyrus and right cerebellar lobule IX was observed in the default
      network of BAFME. Enhanced functional connectivity of the left cerebellar lobule
      VIII with the bilateral middle temporal gyri, right putamen, and left cerebellar
      crus I was found in the dorsal attention network of BAFME. Enhanced functional
      connectivity between the left cerebellar lobule VIIb and right frontal pole was
      found in the control network of BAFME. SIGNIFICANCE: Altered cerebellar-cerebral
      functional connectivity may contribute to the understanding of the nosogenesis of
      BAFME and explain the cognitive dysfunction in this Chinese family with BAFME.

PMID- 27037792
TI  - Target gene enrichment in the cyclophyllidean cestodes, the most diverse group of
      tapeworms.
AB  - The Cyclophyllidea is the most diverse order of tapeworms, encompassing species
      that infect all classes of terrestrial tetrapods including humans and
      domesticated animals. Available phylogenetic reconstructions based either on
      morphology or molecular data lack the resolution to allow scientists to either
      propose a solid taxonomy or infer evolutionary associations. Molecular markers
      available for the Cyclophyllidea mostly include ribosomal DNA and mitochondrial
      loci. In this study, we identified 3641 single-copy nuclear coding loci by
      comparing the genomes of Hymenolepis microstoma, Echinococcus granulosus and
      Taenia solium. We designed RNA baits based on the sequence of H. microstoma, and
      applied target enrichment and Illumina sequencing to test the utility of those
      baits to recover loci useful for phylogenetic analyses. We captured DNA from five
      species of tapeworms representing two families of cyclophyllideans. We obtained
      an average of 3284 (90%) of the targets from the test samples and then used
      captured sequences (2 181 361 bp in total; fragment size ranging from 301 to 6969
      bp) to reconstruct a phylogeny for the five test species plus the three species
      for which genomic data are available. The results were consistent with the
      current consensus regarding cyclophyllidean relationships. To assess the
      potential for our method to yield informative genetic variation at intraspecific
      scales, we extracted 14 074 single nucleotide polymorphisms (SNPs) from
      alignments of four Arostrilepis macrocirrosa and two A. cooki and successfully
      inferred their relationships. The results showed that our target gene tools yield
      data sets that provide robust inferences at a range of taxonomic scales in the
      Cyclophyllidea. 

PMID- 27037793
TI  - Vertical stiffness asymmetries during drop jumping are related to ankle stiffness
      asymmetries.
AB  - Asymmetry in vertical stiffness has been associated with increased injury
      incidence and impaired performance. The determinants of vertical stiffness
      asymmetry have not been previously investigated. Eighteen healthy men performed
      three unilateral drop jumps during which vertical stiffness and joint stiffness
      of the ankle and knee were calculated. Reactive strength index was also
      determined during the jumps using the ratio of flight time to ground contact
      time. "Moderate" differences in vertical stiffness (t17  = 5.49; P < 0.001),
      "small" differences in center of mass displacement (t17  = -2.19; P = 0.043), and
      "trivial" differences in ankle stiffness (t17  = 2.68; P = 0.016) were observed
      between stiff and compliant limbs. A model including ankle stiffness and reactive
      strength index symmetry angles explained 79% of the variance in vertical
      stiffness asymmetry (R2  = 0.79; P < 0.001). None of the symmetry angles were
      correlated to jump height or reactive strength index. Results suggest that
      asymmetries in ankle stiffness may play an important role in modulating vertical
      stiffness asymmetry in recreationally trained men.

PMID- 27037794
TI  - Annexin A2, an essential partner of the exocytotic process in chromaffin cells.
AB  - Annexin A2 is a calcium-, actin-, and lipid-binding protein implicated in
      exocytosis in different cell types, such as neuroendocrine cells. In chromaffin
      cells, cytosolic annexin A2 is recruited to the plasma membrane upon cell
      stimulation. Here, we review the latest evidence detailing the functional
      importance of annexin A2 in different stages of exocytosis. These include the
      recruitment of annexin A2 to the plasma membrane near soluble N-ethylmaleimide
      sensitive factor attachment protein receptor complexes, the role of annexin A2 in
      the formation of lipid domains at exocytotic sites, and finally the annexin A2
      bundling of actin microfilaments associated with chromaffin granules. These
      structures induce first the coalescence of lipid domains required for the
      formation of the exocytotic site, and in the second time, exert mechanical force
      on the granule to favor fusion pore expansion and squeeze the granule to
      facilitate catecholamine release. Annexin A2 is a calcium-, actin-, and lipid
      binding protein implicated in exocytosis in different cell types, including
      neuroendocrine cells. Upon cell stimulation, annexin A2 translocates from the
      cytosol to the plasma membrane of chromaffin cells and bundles actin filaments
      associated with chromaffin granules. This promotes the formation of lipid domains
      required for granule docking, and facilitates catecholamine release by
      compressing the granule. This article is part of a mini review series on
      Chromaffin cells (ISCCB Meeting, 2015).

PMID- 27037795
TI  - Retention Load of Telescopic Crowns with Different Taper Angles between Cobalt
      Chromium and Polyetheretherketone Made with Three Different Manufacturing
      Processes Examined by Pull-Off Test.
AB  - PURPOSE: To investigate the retention loads of differently fabricated secondary
      telescopic polyetheretherketone (PEEK) crowns on cobalt-chromium primary crowns
      with different tapers. MATERIALS AND METHODS: Cobalt-chromium primary crowns with
      0 degrees , 1 degrees , and 2 degrees  tapers were constructed, milled, and
      sintered. Corresponding secondary crowns were fabricated by milling, pressing
      from pellets, and pressing from granules. For these nine test groups, the pull
      off tests of each crown combination were performed 20 times, and the retention
      loads were measured (Zwick 1445, 50 mm/min). Data were analyzed using linear
      regression, covariance analysis, mixed models, Kruskal-Wallis, and Mann-Whitney U
      test, together with the Benferroni-Holm correction. RESULTS: The mixed models
      covariance analysis reinforced stable retention load values (p = 0.162) for each
      single test sequence. There was no interaction between the groups and the
      separation cycles (p = 0.179). Milled secondary crowns with 0 degrees  showed the
      lowest mean retention load values compared to all tested groups (p = 0.003)
      followed by those pressed form pellets with 1 degrees . Regarding the different
      tapers, no effect of manufacturing method on the results was observed within 1
      degrees  and 2 degrees  groups (p = 0.540; p = 0.052); however, among the 0
      degrees  groups, the milled ones showed significantly the lowest retention load
      values (p = 0.002). Among the manufacturing methods, both pressed groups showed
      no impact of taper on the retention load values (p > 0.324 and p > 0.123,
      respectively), whereas among the milled secondary crowns, the 0 degrees  taper
      showed significantly lower retention load values than the 1 degrees  and 2
      degrees  taper (p < 0.002). CONCLUSION: Based on these results, telescopic crowns
      made of PEEK seem to show stable retention load values for each test sequence;
      however, data with thermo-mechanical aging are still required. In addition,
      further developments in CAD/CAM manufacturing of PEEK materials for telescopic
      crowns are warranted, especially for 0 degrees .

PMID- 27037796
TI  - Predicting human intestinal absorption in the presence of bile salt with micellar
      liquid chromatography.
AB  - Understanding intestinal absorption for pharmaceutical compounds is vital to
      estimate the bioavailability and therefore the in vivo potential of a drug. This
      study considers the application of micellar liquid chromatography (MLC) to
      predict passive intestinal absorption with a selection of model compounds. MLC is
      already known to aid prediction of absorption using simple surfactant systems;
      however, with this study the focus was on the presence of a more complex, bile
      salt surfactant, as would be encountered in the in vivo environment. As a result,
      MLC using a specific bile salt has been confirmed as an ideal in vitro system to
      predict the intestinal permeability for a wide range of drugs, through the
      development of a quantitative partition-absorption relationship. MLC offers many
      benefits including environmental, economic, time-saving and ethical advantages
      compared with the traditional techniques employed to obtain passive intestinal
      absorption values. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27037797
TI  - Power/sample size calculations for assessing correlates of risk in clinical
      efficacy trials.
AB  - In a randomized controlled clinical trial that assesses treatment efficacy, a
      common objective is to assess the association of a measured biomarker response
      endpoint with the primary study endpoint in the active treatment group, using a
      case-cohort, case-control, or two-phase sampling design. Methods for power and
      sample size calculations for such biomarker association analyses typically do not
      account for the level of treatment efficacy, precluding interpretation of the
      biomarker association results in terms of biomarker effect modification of
      treatment efficacy, with detriment that the power calculations may tacitly and
      inadvertently assume that the treatment harms some study participants. We develop
      power and sample size methods accounting for this issue, and the methods also
      account for inter-individual variability of the biomarker that is not
      biologically relevant (e.g., due to technical measurement error). We focus on a
      binary study endpoint and on a biomarker subject to measurement error that is
      normally distributed or categorical with two or three levels. We illustrate the
      methods with preventive HIV vaccine efficacy trials and include an R package
      implementing the methods. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037798
TI  - Adaptation to low temperatures in the wild tomato species Solanum chilense.
AB  - Molecular adaptation to abiotic stresses in plants is a complex process based
      mainly on the modifications of gene transcriptional activity and the alteration
      of protein-protein interactions. We used a combination of population genetic,
      comparative transcriptomic and plant physiology approaches to investigate the
      mechanisms of adaptation to low temperatures in Solanum chilense populations
      distributed along Andean altitudinal gradients. We found that plants from all
      populations have high chilling tolerance, which does not correlate with
      temperatures in their native habitats. In contrast, tolerance to freezing shows a
      significant association with altitude and temperature variables. We also observed
      the differences in expression patterns of cold-response genes between plants from
      high- and low-altitude populations. These results suggest that genetic
      adaptations to low temperatures evolved in high-altitude populations of S.
      chilense. At the transcriptional level, these adaptations may include high levels
      of constitutive expression of the genes encoding ICE1, the key transcription
      factor of the cold signalling pathway, and chloroplast omega-3 fatty acid
      desaturase FAD7. At the sequence level, a signature of selection associated with
      the adaptation to high altitudes was detected at the C-terminal part of ICE1
      encoding the ACT regulatory domain.

PMID- 27037799
TI  - Wide to Narrow QRS Tachycardia: What Is the Mechanism?

PMID- 27037800
TI  - PLURIPETALA mediates ROP2 localization and stability in parallel to SCN1 but
      synergistically with TIP1 in root hairs.
AB  - Prenylation, the post-translational attachment of prenyl groups to substrate
      proteins, can affect their distribution and interactomes. Arabidopsis PLURIPETALA
      (PLP) encodes the shared alpha subunit of two heterodimeric protein
      isoprenyltransferases, whose functional loss provides a unique opportunity to
      study developmental and cellular processes mediated by its prenylated substrates,
      such as ROP GTPases. As molecular switches, the distribution and activation of
      ROPs are mediated by various factors, including guanine nucleotide exchange
      factors, GTPase activating proteins, guanine nucleotide dissociation inhibitors
      (RhoGDIs), prenylation, and S-acylation. However, how these factors together
      ensure that dynamic ROP signalling is still obscure. We report here that a loss
      of-function allele of PLP resulted in cytoplasmic accumulation of ROP2 in root
      hairs and reduced its stability. Consequently, two downstream events of ROP
      signalling, i.e. actin microfilament (MF) organization and the production of
      reactive oxygen species (ROS), were compromised. Genetic, cytological and
      biochemical evidence supports an additive interaction between prenylation and
      RhoGDI1/SCN1 in ROP2 distribution and stability whereas PLP acts synergistically
      with the protein S-acyl transferase TIP GROWTH DEFECTIVE1 during root hair
      growth. By using root hair growth as a model system, we uncovered complex
      interactions among prenylation, RhoGDIs, and S-acylation in dynamic ROP
      signalling.

PMID- 27037801
TI  - Micro-CT evaluation of the quality of root fillings when using three root filling
      systems.
AB  - AIM: To evaluate the percentage volumes of filling materials and voids in single
      rooted teeth filled with three different filling systems using micro-computed
      tomography (micro-CT). METHODOLOGY: Thirty single-rooted human teeth were used.
      After preparation of the root canals, the teeth were randomly divided into three
      groups (n = 10). The canals were filled with EndoREZ, ActiV GP or AH Plus/gutta
      percha. Each specimen was scanned using a micro-CT device at a resolution of
      13.68 MUm. Percentage volumes of root filling materials and voids were calculated
      and data were analysed statistically using the Kruskal-Wallis test and the Mann
      Whitney U-test with Bonferroni adjustment. Within each group, the Friedman test
      was performed with the Wilcoxon signed-rank test to detect discrepancies.
      RESULTS: The percentage volume of filling material was significantly lower in the
      ActiV GP group than in the other groups (P < 0.05), whilst the percentage volume
      of voids was significantly higher in the ActiV GP group than in the other groups
      (P < 0.05). CONCLUSION: None of the systems were associated with void-free root
      fillings. The ActiV GP system had a significantly higher percentage volume of
      voids than the other systems.

PMID- 27037802
TI  - Continuous evolution of magnetic resonance imaging in multiple sclerosis.

PMID- 27037803
TI  - A case of cervical esophageal duplication cyst in a newborn infant.
AB  - Esophageal duplication cyst is a rare congenital anomaly resulting from a foregut
      budding error during the fourth to sixth week of embryonic development. Cervical
      esophageal duplication cysts are very rare and may cause respiratory distress in
      infancy. A full-term newborn girl who was born by normal delivery was transferred
      to our hospital because of swelling of the right anterior neck since birth.
      Cervical ultrasonography showed a 40 * 24 * 33 mm simple cyst on the right neck.
      Tracheal intubation was required at 2 weeks of age because of worsening external
      compression of the trachea. Fine-needle aspiration cytology revealed the
      existence of ciliated epithelium. At 1 month of age, exploration was performed
      through a transverse neck incision. The cyst had a layer of muscle connected to
      the lateral wall of the esophagus. Histopathological diagnosis was a cervical
      esophageal duplication cyst. We describe the clinical features of infantile
      cervical esophageal duplication cysts based on our experience of this rare
      disease in a neonate, along with a review of 19 cases previously reported in
      literature. 

PMID- 27037804
TI  - Malignant hepatic epithelioid angiomyolipoma with recurrence in the lung 7 years
      after hepatectomy: a case report and literature review.
AB  - Angiomyolipoma (AML) arising in the liver is rare and usually benign, but it
      occasionally has malignant potential. A 58-year-old man with a liver tumor
      identified by a previous doctor with features suggestive of hepatocellular
      carcinoma on computed tomography (CT) underwent anterior segmentectomy of the
      liver in 2006. Microscopically, the tumor was composed of exclusively epithelioid
      cells that were scatteredly positive for human melanoma black 45 on
      immunohistochemistry. Accordingly, primary hepatic epithelioid AML (eAML) was
      diagnosed. The patient was subsequently referred to our hospital for follow-up
      after hepatectomy. He had event-free survival for nearly 7 years. In 2013, two
      well-defined round nodules were detected in the right lung field by chest CT, and
      partial pneumonectomy was performed for diagnosis and treatment. Histological
      examination of the resected lung tissue showed that it was morphologically and
      immunohistochemically identical to his primary hepatic eAML, leading to the
      diagnosis of pulmonary metastasis. This paper demonstrates a rare case of
      malignant hepatic eAML with late recurrence in the lung after hepatectomy. 

PMID- 27037805
TI  - Treatment of periprosthetic acetabular fractures after previous hemi- or total
      hip arthroplasty: Introduction of a new implant.
AB  - OBJECTIVE: Treatment of displaced periprosthetic acetabular fractures in elderly
      patients. The goal is to stabilize an acetabular fracture independent of the
      fracture pattern, by inserting the custom-made roof-reinforcement plate and
      starting early postoperative full weight-bearing mobilization. INDICATIONS:
      Acetabular fracture with or without previous hemi- or total hip arthroplasty.
      CONTRAINDICATIONS: Non-displaced acetabular fractures. SURGICAL TECHNIQUE: Watson
      Jones approach to provide accessibility to the anterior and supraacetabular part
      of the iliac bone. Angle-stable positioning of the roof-reinforcement plate
      without any fracture reduction. Cementing a polyethylene cup into the metal plate
      and restoring prosthetic femoral components. POSTOPERATIVE MANAGEMENT: Full
      weight-bearing mobilization within the first 10 days after surgery. In cases of
      two column fractures, partial weight-bearing is recommended. RESULTS: Of 7
      patients with periprosthetic acetabular fracture, 5 were available for follow-up
      at 3, 6, 6, 15, and 24 months postoperatively. No complications were recognized
      and all fractures showed bony consolidation. Early postoperative mobilization was
      started within the first 10 days. All patients except one reached their preinjury
      mobility level. This individual and novel implant is custom made for displaced
      acetabular and periprosthetic fractures in patients with osteopenic bone. It
      provides a hopeful benefit due to early full weight-bearing mobilization within
      the first 10 days after surgery. LIMITATIONS: In case of largely destroyed
      supraacetabular bone or two-column fractures according to Letournel additional
      synthesis via an anterior approach might be necessary. In these cases partial
      weight bearing is recommended.

PMID- 27037806
TI  - Implantation of a Novel Allogeneic Mesenchymal Precursor Cell Type in Patients
      with Ischemic Cardiomyopathy Undergoing Coronary Artery Bypass Grafting: an Open
      Label Phase IIa Trial.
AB  - Heart failure is a life-limiting condition affecting over 40 million patients
      worldwide. Ischemic cardiomyopathy (ICM) is the most common cause. This study
      investigates in situ cardiac regeneration utilizing precision delivery of a novel
      mesenchymal precursor cell type (iMP) during coronary artery bypass surgery
      (CABG) in patients with ischemic cardiomyopathy (LVEF < 40 %). The phase IIa
      safety study was designed to enroll 11 patients. Preoperative scintigraphy
      imaging (SPECT) was used to identify hibernating myocardium not suitable for
      conventional myocardial revascularization for iMP implantation. iMP cells were
      implanted intramyocardially in predefined viable peri-infarct areas that showed
      poor perfusion, which could not be grafted due to poor target vessel quality.
      Postoperatively, SPECT was then used to identify changes in scar area.
      Intramyocardial implantation of iMP cells with CABG was safe with preliminary
      evidence of efficacy of improved myocardial contractility and perfusion of
      nonrevascularized territories resulting in a significant reduction in left
      ventricular scar area at 12 months after treatment. Clinical improvement was
      associated with a significant improvement in quality of life at 6 months
      posttreatment in all patients. The results suggest the potential for in situ
      myocardial regeneration in ischemic heart failure by delivery of iMP cells.

PMID- 27037807
TI  - Youth-Adult Partnerships and Youth Identity Style.
AB  - Youth-adult partnerships (e.g., youth leading programs, participating as members
      of advisory boards) are a common and widely recommended practice in youth work
      and youth-serving program settings. Although researchers have suggested that
      these opportunities contribute to youth's identity development, empirical
      evidence is lacking. In the current study, we tested associations between
      identity style and degree of youth voice, collaborative youth-adult
      relationships, and youth's program engagement in 194 youth participating in youth
      adult partnerships (M age = 17.6, 62 % female). We found that these
      characteristics of youth-adult partnerships predicted higher informational
      identity style, although only program engagement emerged as a unique predictor.
      Furthermore, exploratory analysis indicated that these associations were
      moderated by the type of organization. The findings suggest the need for more
      research on the multiple dimensions of youth-adult partnerships and their
      association with youth functioning, as well as pointing to the importance of the
      broader organizational context of youth-adult partnerships.

PMID- 27037808
TI  - Adrenergic Effect on Cytokine Release After Ex Vivo Healthy Volunteers' Whole
      Blood LPS Stimulation.
AB  - Catecholamines are molecules with immunomodulatory properties in health and
      disease. Several studies showed the effect of catecholamines when administered to
      restore hemodynamic stability in septic patients. This study investigates the
      effect of norepinephrine and dobutamine on whole blood cytokine release after ex
      vivo lipopolysaccharide (LPS) stimulation. Whole blood collected from healthy
      individuals was stimulated with LPS, in the presence of norepinephrine or
      dobutamine at different concentrations, with or without metoprolol, a beta1
      receptor antagonist. Cytokine measurement was performed in isolated cell culture
      supernatants with ELISA. Results are expressed as mean +/- SEM and compared with
      Mann-Whitney rank-sum test. Both norepinephrine and dobutamine significantly
      reduced TNF-alpha and IL-6 production after ex vivo LPS stimulation of whole
      blood in a dose-dependent manner, and this effect was partially reversed by the
      presence of metoprolol. Norepinephrine and dobutamine reduce the LPS-induced
      production of pro-inflammatory cytokines, thus possibly contributing to altered
      balance between the inflammatory and anti-inflammatory responses, which are vital
      for a successful host response to severe disease, shock, and sepsis. 

PMID- 27037809
TI  - MRI of the tibioastragalus anticus of Gruber muscle: a rare accessory muscle and
      normal anatomical variant.
AB  - We present the case of a 31-year-old man who sustained a hyperplantar flexion
      injury of his right ankle, and was evaluated using computed tomography and MRI to
      assess for osseous and ligamentous injury. The MRI and CT studies demonstrated a
      tibioastragalus anticus of Gruber (TAAG) muscle in the lower limb's anterior
      compartment. To our knowledge, the imaging of this muscle has not been previously
      described. The TAAG muscle arises from the lower third of the anterolateral tibia
      and the interosseous membrane. Its tendon passes laterally, deep to the tibialis
      anterior and extensor hallucis longus tendons, and inserts onto the anterior
      superolateral neck of the talus in a fan-like manner. Knowledge and recognition
      of this tendon are important for both diagnostic accuracy and surgical planning,
      and could potentially be used as a tendon transfer or graft in the appropriate
      clinical setting. The presence of this accessory muscle should not be confused
      with a pathological condition. 

PMID- 27037810
TI  - Prevalence of asymptomatic chondrocalcinosis in the pelvis.
AB  - OBJECTIVE: To determine trends in incidentally detected age- and gender
      associated chondrocalcinosis on pelvic CT. MATERIALS AND METHODS: Twenty patients
      of each gender at the center of each decade of life who underwent a CT scan of
      the pelvis performed 2009-2013 were identified and selected for a total of 400
      pelvic CTs. Images were reviewed independently by two radiologists for the
      presence or absence of chondrocalcinosis within the pelvis. Patients with hip or
      low back pain, known CPPD arthropathy or any known predisposing condition, prior
      hip arthroplasty, or articular fracture were excluded. Logistic regression was
      used to predict the presence/absence of chondrocalcinosis as a function of
      patient age and gender. RESULTS: The presence/absence of chondrocalcinosis was
      found to be associated with patient age (p = 0.016) but not patient gender (p =
      0.929). In the pelvis, chondrocalcinosis was most frequently identified at the
      pubic symphysis. Incidental chondrocalcinosis was not identified in any patients
      under 50 years of age. Chondrocalcinosis increased in frequency from 12.5 at 55
      years of age to 27.5 % of patients 95 years of age. CONCLUSIONS:
      Chondrocalcinosis is common and more prevalent in late adulthood, occurs without
      a gender predilection, and is infrequently identified in patients younger than 50
      years of age.

PMID- 27037811
TI  - A multicenter study on the relative effectiveness of a 12-week physical training
      program for adults with an oncologic diagnosis.
AB  - PURPOSE: The purpose of this study was to examine the association between cancer
      survivors' socio-demographic and clinical characteristics and aerobic fitness
      changes following a physical training program. METHODS: We assessed the
      association between participant's characteristics and aerobic fitness in the six
      min walk test (6MWT) after a 12-week LIVESTRONG(r) at Young Men's Christian
      Association (YMCA) exercise program for adults with an oncologic diagnosis using
      linear mixed effects models. RESULTS: Fifty-one percent of participants had a
      breast cancer diagnosis and 22 % had received treatment within 1 year of
      enrollment. At baseline, participants who reported good/excellent health status
      performed better in the 6MWT than those who reported poor/fair health status
      (384.2 vs. 345.0 m, p = 0.035). After 12 weeks, all participants increased their
      average 6MWT performance by 54.2 m. After adjustment for age, gender, physical
      activity level, and smoking status, participants who were 60 years old or younger
      had a greater increase in the 6MWT score than participants older than 60 years
      (63.2 vs. 43.9 m, p = 0.041) while those who had never been YMCA members had a
      greater increase in the 6MWT compared to those who had ever been a YMCA member
      (62.2 vs. 40.3 m, p = 0.041). CONCLUSION: Overall, aerobic fitness among adults
      with an oncologic diagnosis increased after a 12-week exercise program,
      particularly among participants who were 60 years old or younger or were not YMCA
      members at enrollment. Participants with poorer health had lower aerobic fitness
      at baseline, though they had a similar positive response to the program as
      healthier participants. Future study designs may include randomization and an
      additional untreated arm.

PMID- 27037812
TI  - "An addendum to breast cancer": the triple negative experience.
AB  - PURPOSE: The triple negative breast cancer (TNBC) subtype, known to be aggressive
      with high recurrence and mortality rates, disproportionately affects African
      Americans, young women, and BRCA1 carriers. TNBC does not respond to hormonal or
      biologic agents, limiting treatment options. The unique characteristics of the
      disease and the populations disproportionately affected indicate a need to
      examine the responses of this group. No known studies describe the psychosocial
      experiences of women with TNBC. The purpose of this study is to begin to fill
      that gap and to explore participants' psychosocial needs. METHOD: An interpretive
      descriptive qualitative approach was used with in-depth interviews. A purposive
      sample of adult women with TNBC was recruited. Dominant themes were extracted
      through iterative and constant comparative analysis. RESULTS: Of the 22
      participants, nearly half were women of color, and the majority was under the age
      of 60 years and within 5 years of diagnosis. The central theme was a perception
      of TNBC as "an addendum" to breast cancer. There were four subthemes: TNBC is
      Different: "Bottom line, it's not good"; Feeling Insecure: "Flying without a
      net"; Decision-Making and Understanding: "A steep learning curve"; and Looking
      Back: "Coulda, shoulda, woulda." Participants expressed a need for support in
      managing intense uncertainty with a TNBC diagnosis and in decision-making.
      CONCLUSIONS: Women with all subtypes of breast cancer have typically been studied
      together. This is the first study on the psychosocial needs specifically of women
      with TNBC. The findings suggest that women with TNBC may have unique experiences
      and unmet psychosocial needs.

PMID- 27037813
TI  - A systematic review of patient-reported outcome measures of neuropathy in
      children, adolescents and young adults.
AB  - PURPOSE: Peripheral neuropathy is an important, yet poorly studied, side effect
      of pediatric cancer treatment. There are many measures of patient-reported
      peripheral neuropathy in adults but very few in children. We aimed to
      systematically review and summarize reliable and valid patient-reported
      peripheral neuropathy scales used in pediatrics. METHODS: Four major electronic
      databases (Medline, Embase, EBSCO Host in Cumulative Index to Nursing and Allied
      Health Literature, and PsycINFO) were reviewed for studies that measured
      peripheral neuropathy in pediatric patients. Studies eligible for inclusion were
      those that described use of any patient-reported scale of peripheral neuropathy
      among children, adolescents, and young adults with any underlying diagnosis (not
      limited to cancer). RESULTS: From a total of 765 articles retrieved, 5 met
      eligibility criteria and were included. One was a neuropathy symptom score used
      in patients with diabetes, and the remaining four were in oncology patients and
      all were based on the total neuropathy score. All involved objective assessments
      conducted by trained professionals; none relied purely on patient report.
      CONCLUSIONS: There are no validated instruments that consist solely of a patient
      reported outcome measure of neuropathy in pediatrics and adolescents. Because the
      clinical evaluation of neuropathy requires specialized training, it is not
      generalizable in large studies conducted in many diverse institutions. Future
      studies should validate adult patient-reported neuropathy scales in pediatric and
      adolescent populations, or develop novel instruments designed for this
      population.

PMID- 27037814
TI  - Dosimetric predictors of acute hematologic toxicity during concurrent intensity
      modulated radiotherapy and chemotherapy for anal cancer.
AB  - PURPOSE: This study aimed at investigating whether the irradiated volume of
      pelvic bone marrow (PBM) and specific subsites may predict the occurrence of
      acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent
      chemo-radiation. METHODS: 50 patients, submitted to IMRT and concurrent
      chemotherapy, were analyzed. Several bony structures were defined on planning-CT:
      PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On
      dose-volume histograms, dosimetric parameters were taken. Endpoints included
      white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb)
      and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring
      scale. Generalized linear modeling was used to find correlations between
      dosimetric variables and blood cell nadirs, while logistic regression analysis
      was used to test correlation with >=G3 HT. Receiver Operating Characteristic
      (ROC) curve analysis was used to evaluate the optimal cut-off points for
      predictive dosimetric variables with the Youden method. RESULTS: Maximum detected
      acute HT comprised 38 % of >=G3 leukopenia and 32 % of >=G3 neutropenia. Grade 2
      anemia was observed in 4 % of patients and >=G3 thrombocytopenia in 10 %. On
      multivariate analysis a higher PBM-V 20 was associated with lower WBC nadir.
      Increased LSBM-V 40 was correlated with a higher likelihood to develop >=G3 HT. A
      cut-off point at 41 % for LSBM-V 40 was found. Patients with LSBM-V 40 >=41 %
      were more likely to develop >=G3 HT (55.3 vs. 32.4 %; p < 0.01). CONCLUSIONS:
      Increased low-dose to pelvic bony structures significantly predicted for WBC
      decrease. Medium-high dose to specific osseous subsites was associated with a
      higher probability of HT. LSBM-V 40 was a strong predictor of >=G3 HT. A
      threshold at 41 % for LSBM-V 40 could be used to limit HT.

PMID- 27037815
TI  - Is regorafenib providing clinically meaningful benefits to pretreated patients
      with metastatic colorectal cancer?
AB  - Treatment with regorafenib has demonstrated statistically significant
      improvements in terms of overall survival, progression-free survival and disease
      control when compared with placebo in pretreated patients with metastatic
      colorectal cancer in two placebo-controlled, randomized, phase III trials
      (CORRECT and CONCUR). Similar results were observed in two open-label, single-arm
      studies (REBECCA and CONSIGN) performed in the real-world setting. But several
      authors have suggested that the benefit provided by regorafenib may not be
      clinically meaningful for these patients. Moreover, it has been suggested that
      not all subgroups of patients might benefit from regorafenib. The intention of
      this review is to provide an overview of the existing evidence for regorafenib in
      terms of efficacy, tolerability and quality of life in different subpopulations
      according to clinical and biological characteristics. Additionally, the magnitude
      of the clinical benefit provided by regorafenib to these patients has been
      explored and whether there are poorer outcomes in certain subpopulations.

PMID- 27037816
TI  - Prevalence of liver fluke infection in Irish horses and assessment of a
      serological test for diagnosis of equine fasciolosis.
AB  - BACKGROUND: There is little information on the prevalence of Fasciola hepatica
      infection in the horse population in Ireland or the potential impact of fluke
      infection on animal health. OBJECTIVES: To investigate F. hepatica infection in
      the Irish horse population and to assess the diagnostic potential of an indirect
      enzyme-linked immunosorbent assay (ELISA) based on the F. hepatica recombinant
      cathepsin L1 (CL1) antigen. STUDY DESIGN: Cross-sectional abattoir survey of
      horses for liver fluke status. METHODS: Animals (n = 200) were examined at an
      abattoir between May 2013 and April 2014. Horses were graded ante mortem for body
      condition score. Blood and faeces were collected and livers were examined post
      mortem by gross morphology. A cohort (n = 35) of livers were also examined
      histologically. Haematology and blood biochemistry, including serum liver enzyme
      activities, were measured and faeces were sedimented for egg counts. Serum was
      assayed by indirect ELISA using a recombinant CL1. RESULTS: The prevalence of
      liver fluke infection was 9.5%. There was no correlation between liver fluke
      status and time of year, breed classification, age group, sex, body condition
      score, ante mortem assessment, strongyle infection status, serum liver enzyme
      activities or CL1 concentration. A comparison of the CL1 ELISA in horse sera
      compared with a reference standard diagnosis showed high specificity of 95.6%
      (95% confidence interval [CI] 91.5-98.0%), but low sensitivity of 42.1% (95% CI
      20.2-66.5%). MAIN LIMITATIONS: This study is limited by its nature as an abattoir
      study, the relatively small number of animals examined (n = 200), and the absence
      of a known negative group of horses. CONCLUSIONS: Blood biomarkers are not good
      indicators of liver fluke infection and the CL1 ELISA is not a sensitive tool for
      diagnosis of fluke infection in the horse. The prevalence of F. hepatica in
      horses indicates that further research is required to assess the potential impact
      of liver fluke on equine liver health.

PMID- 27037817
TI  - Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion
      in Chinese Children.
AB  - BACKGROUND AND OBJECTIVE: Dexmedetomidine is a highly selective alpha2
      adrenoceptor agonist with sedative and analgesic properties which is also used in
      pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been
      studied in pediatric patients, there are no data for Chinese children available.
      As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was
      the aim of this study to characterize the pharmacokinetics of dexmedetomidine in
      Chinese pediatric patients. METHODS: Thirty-nine children aged 1-9 years
      undergoing surgery were enrolled in the study. Dexmedetomidine was administered
      as short intravenous infusion of 1-2 ug/kg in 10 min. Venous blood samples were
      drawn until 480 min after stopping of infusion. Dexmedetomidine plasma
      concentrations were measured with high-performance liquid chromatography and mass
      spectrometry. Pharmacokinetic modeling was performed by population analysis using
      linear compartment models. RESULTS: Data of 36 patients (age 1-9 years, weight 10
      27 kg) were analyzed. The pharmacokinetics of dexmedetomidine were best described
      by a two-compartment model with an allometric power model and estimates
      standardized to 70 kg body weight. The population estimates (95 % CI) per 70 kg
      bodyweight were: clearance 36.2 (33.3-41.1) l/h, central volume of distribution
      84.3 (70.3-91.4) l, intercompartmental clearance 82.8 (63.6-136.6) l/h,
      peripheral volume of distribution 114 (95-149) l, and terminal half-life 4.4 (3.6
      5.3) h. Age did not show any influence on weight-adjusted parameters.
      CONCLUSIONS: Chinese children showed a similar clearance, but larger volumes of
      distribution and longer terminal half-life when compared to studies in
      Caucasians. TRIAL REGISTRATION: ChiCTR-OPC-14005659.

PMID- 27037818
TI  - Prediction of intrinsically disordered regions in proteins using signal
      processing methods: application to heat-shock proteins.
AB  - Heat-shock protein (HSP)-based immunotherapy is believed to be a promising area
      of development for cancer treatment as such therapy is characterized by a unique
      approach to every tumour. It was shown that by inhibition of HSPs it is possible
      to induce apoptotic cell death in cancer cells. Interestingly, there are a great
      number of disordered regions in proteins associated with cancer, cardiovascular
      and neurodegenerative diseases, signalling, and diabetes. HSPs and some specific
      enzymes were shown to have these disordered regions in their primary structures.
      The experimental studies of HSPs confirmed that their intrinsically disordered
      (ID) regions are of functional importance. These ID regions play crucial roles in
      regulating the specificity of interactions between dimer complexes and their
      interacting partners. Because HSPs are overexpressed in cancer, predicting the
      locations of ID regions and binding sites in these proteins will be important for
      developing novel cancer therapeutics. In our previous studies, signal processing
      methods have been successfully used for protein structure-function analysis (i.e.
      for determining functionally important amino acids and the locations of protein
      active sites). In this paper, we present and discuss a novel approach for
      predicting the locations of ID regions in the selected cancer-related HSPs.

PMID- 27037819
TI  - Using codispersion analysis to quantify and understand spatial patterns in
      species-environment relationships.
AB  - The analysis of spatial patterns in species-environment relationships can provide
      new insights into the niche requirements and potential co-occurrence of species,
      but species abundance and environmental data are routinely collected at different
      spatial scales. Here, we investigate the use of codispersion analysis to measure
      and assess the scale, directionality and significance of complex relationships
      between plants and their environment in large forest plots. We applied
      codispersion analysis to both simulated and field data on spatially located tree
      species basal area and environmental variables. The significance of the observed
      bivariate spatial associations between the basal area of key species and
      underlying environmental variables was tested using three null models.
      Codispersion analysis reliably detected directionality (anisotropy) in bivariate
      species-environment relationships and identified relevant scales of effects. Null
      model-based significance tests applied to codispersion analyses of forest plot
      data enabled us to infer the extent to which environmental conditions, tree sizes
      and/or tree spatial positions underpinned the observed basal area-environment
      relationships, or whether relationships were a result of other unmeasured
      factors. Codispersion analysis, combined with appropriate null models, can be
      used to infer hypothesized ecological processes from spatial patterns, allowing
      us to start disentangling the possible drivers of plant species-environment
      relationships.

PMID- 27037820
TI  - Anterocollis and startle myoclonus due to Lyme meningomyeloradiculitis.

PMID- 27037821
TI  - The relationships of motor-evoked potentials to hand dexterity, motor function,
      and spasticity in chronic stroke patients: a transcranial magnetic stimulation
      study.
AB  - The standardization of patient evaluation and monitoring methods has a special
      importance in evaluating the effectiveness of therapeutic methods using drugs or
      rehabilitative techniques in stroke rehabilitation. The aim of this study was to
      investigate the relationships between clinical instruments and transcranial
      magnetic stimulation (TMS)-evoked neurophysiological parameters in stroke
      patients. This study included 22 chronic post-stroke patients who were clinically
      assessed using the Motricity Index (MI), finger-tapping test (FTT), Motor
      Activity Log (MAL) 28, Brunnstrom motor staging and Ashworth Scale (ASH). Motor
      evoked potential (MEP) latency and amplitude, resting motor threshold (rMT) and
      central motor conduction time (CMCT) were measured with TMS. Shorter MEP-latency,
      shorter CMCT, higher motor-evoked potential amplitude, and diminished rMT
      exhibited significant correlations with clinical measures evaluating motor stage,
      dexterity, and daily life functionality. rMT exhibited a negative correlation
      with hand and lower extremity Brunnstrom stages (r = -0.64, r = -0.51,
      respectively), MI score (r = -0.48), FTT score (r = -0.69), and also with amount
      of use scale and quality of movement scale of MAL 28 scores (r = -0.61, r = 
      0.62, respectively). Higher MEP amplitude and diminished rMT showed positive
      correlations with reduced ASH score (r = -0.65, r = 0.44, respectively). The TMS
      evoked neurophysiologic parameters including MEP latency, amplitude, rMT and CMCT
      generally have positive correlation with clinical measures which evaluate motor
      stage, dexterity and daily life functionality. Additionally, spasticity has also
      remarkable relationships with MEP amplitude and rMT. These results suggest that
      TMS-evoked neurophysiological parameters were useful measures for monitoring post
      stroke patients.

PMID- 27037822
TI  - Mapping the intrinsically disordered properties of the flexible loop domain of
      Bcl-2: a molecular dynamics simulation study.
AB  - Most of the B-cell lymphoma-2 (Bcl-2) protein structure has been elucidated;
      however, the conformation of its flexible loop domain (FLD) has not yet been
      experimentally predicted. Its high flexibility under physiological conditions is
      the reason. FLD behaves as an intrinsically disordered region (IDR) and can adopt
      regular structures in particular conditions associated with the control of Bcl
      2's anti-apoptotic functions. In a previous contribution, we analyzed an
      engineered Bcl-2 construct (Bcl-2-Delta22Sigma3) submitted to 25-ns MD and
      reported a disordered-to-helix transitions in a region of FLD (rFLD, residues 60
      77). However, the conformational preferences in solution of rFLD in the
      nanosecond to microsecond scale were not analyzed. Herein, an average model was
      obtained for the native Bcl-2 protein by homology modeling and MD simulation
      techniques. From this, only the atomic coordinates corresponding to the rFLD were
      simulated for 1 MUs by MD at 310 K. In concordance with previous studies, a
      disordered-to-helix transitions were exhibited, implying that this
      "interconversion of folding" in the rFLD suggest a possible set of conformations
      encoded in its sequence. Principal component analysis (PCA) showed that most of
      the conformational fluctuation of Bcl-2 is provided by rFLD. Dihedral PCA (dPCA)
      offered information about all the conformations of rFLD in the MUs of the
      simulation, characterizing a dPCA-based free energy landscape of rFLD, and a
      conformational ensemble of fast interconverting conformations as other IDRs.
      Furthermore, despite the conformational heterogeneity of rFLD, the analysis of
      the dihedral angles (Phi, Psi) showed that this region does not randomly explore
      the conformational space in solution.

PMID- 27037823
TI  - Melt-phase behavior of collapsed PMMA/PVC chains revealed by multiscale
      simulations.
AB  - Single- and double-chain models of three stereoregular polymers, iso- and
      syndiotactic poly(methyl methacrylate) and isotactic poly(vinyl chloride), were
      extensively simulated using systematic coarse-grained (CG) potentials. It was
      found that, in vacuum, all of these long chains collapse in a two-stage process
      from their fully extended configurations into coils, and the two chains in each
      double-chain model ultimately become intertwined. Strong intermolecular
      interactions were found to occur between two chains of the same polymer ("like
      pairs"), which helps to explain the high densities of single-component melts.
      However, the intermolecular interactions between two chains of different polymers
      ("unlike pairs") were stronger than those in like pairs. The enthalpy of mixing
      for unlike pairs-obtained from their intermolecular interaction energies-was
      negative, indicating that the two binary blends considered here are homogeneous
      systems. Moreover, a more negative enthalpy of mixing is suggested to correlate
      with better miscibility. These results agree well with corresponding experimental
      and simulated results, once again validating the accuracy of CG potentials when
      they are used to explore structural and energetic properties. The local structure
      captured by the isolated long chains dictates the ability to elucidate melt-phase
      behavior. A scheme involving the preparation of bulk models with initially
      collapsed chains was proposed; such CG models could be widely used to rapidly
      screen pairs of polymers for specific applications.

PMID- 27037824
TI  - A DFT investigation on the structural and antioxidant properties of new isolated
      interglycosidic O-(1 -> 3) linkage flavonols.
AB  - We present a computational study on two flavonols that were recently isolated
      from Loranthaceae family plant extracts: kaempferol 3-O-alpha-L-arabinofuranosyl
      (1 -> 3)-alpha-L-rhamnoside and quercetin 3-O-alpha-L-arabinofuranosyl-(1 -> 3)
      alpha-L-rhamnoside. Their structures and energetics have been investigated at the
      density functional level of theory, up to B3LYP/6-31+G(d,p), incorporating
      solvent effects with polarizable continuum models. In addition, their potential
      antioxidant activities were probed through the computation of the (i) bond
      dissociation enthalpies (BDEs), which are related to the hydrogen-atom transfer
      mechanism (HAT), and (ii) ionization potentials (IPs), which are related to the
      single-electron transfer mechanism (SET). The BDEs were determined in water to be
      83.23 kcal/mol for kaempferol 3-O-alpha-L-arabinofuranosyl-(1 -> 3)-alpha-L
      rhamnoside and 77.49 kcal/mol for quercetin 3-O-alpha-L-arabinofuranosyl-(1 -> 3)
      alpha-L-rhamnoside. The corresponding IPs were obtained for both compounds as
      133.38 and 130.99 kcal/mol, respectively. The BDEs and IPs are comparable to
      those probed for their parental molecules kaempferol and quercetin; this is in
      marked contrast to previous studies where glycosylation at the 3-position
      increases the corresponding BDEs, and, hence, decreases subsequent antioxidant
      activity. The BDEs and IPs obtained suggest both compounds are promising for
      antioxidant activity and thus further experimental tests are encouraged. 

PMID- 27037825
TI  - Light acclimation of shade-tolerant and light-resistant Tradescantia species:
      induction of chlorophyll a fluorescence and P700 photooxidation, expression of
      PsbS and Lhcb1 proteins.
AB  - In this work, we have compared photosynthetic performance and expression of the
      PsbS and Lhcb1 proteins in two contrast ecotypes of Tradescantia species, T.
      fluminensis (shade-tolerant) and T. sillamontana (light-resistant), grown at two
      intensities of light: 50-125 MUmol photons m-2 s-1 (low light, LL) and 875-1000
      MUmol photons m-2 s-1 (high light, HL). Using the EPR method for measuring the
      P700 content, we have found that LL-grown plants of both species have higher (by
      a factor of ~1.7-1.8) contents of PSI per fresh weight unit as compared to HL
      grown plants. Acclimation of plants to LL or HL irradiation also influences the
      Chl(a + b) level and expression of the PsbS and Lhcb1 proteins. Immunoblotting
      analysis showed that acclimation to HL stimulates (by a factor of ~1.7-1.8) the
      level of PsbS related to the total number of P700 centers. In light-resistant
      species T. sillamontana, the ratio PsbS/P700 is about 2-times higher than in
      shade-tolerant species T. fluminensis grown under the same conditions. This
      should enhance the capacity of their leaves for protection against the light
      stress. In agreement with these observations, the capacity of leaves for NPQ
      induction was enhanced during plant acclimation to HL. Kinetic studies of P700
      photooxidation and light-induced changes in the yield of Chl a fluorescence also
      revealed that the short-term regulation of electron transport processes in
      chloroplasts, which manifested themselves in the kinetics of [Formula: see text]
      induction and the rate of Chl a fluorescence quenching, occurred more rapidly in
      HL-grown plants than in LL-grown plants. Thus, both factors, enhanced expression
      of PsbS and more rapid response of the photosynthetic electron transport chain to
      dark-to-light transitions should increase the capacity of HL-grown plants for
      their resistance to rapid fluctuations of solar light.

PMID- 27037826
TI  - Nanostructured manganese oxide on silica aerogel: a new catalyst toward water
      oxidation.
AB  - Herein we report on the synthesis and characterization of nano-sized Mn
      oxide/silica aerogel with low density as a good catalyst toward water oxidation.
      The composite was synthesized by a simple and low-cost hydrothermal procedure. In
      the next step, we studied the composite in the presence of cerium(IV) ammonium
      nitrate and photo-produced Ru(bpy) 33+ as a water-oxidizing catalyst. The low
      density composite is a good Mn-based catalyst with turnover frequencies of ~0.3
      and 0.5 (mmol O2/(mol Mn.s)) in the presence of Ru(bpy) 33+ and cerium(IV)
      ammonium nitrate, respectively. In addition to the water-oxidizing activities of
      the composite under different conditions, its self-healing reaction in the
      presence of cerium(IV) ammonium nitrate was also studied.

PMID- 27037827
TI  - Learning and memory in the forced swimming test: effects of antidepressants
      having varying degrees of anticholinergic activity.
AB  - The antidepressant-induced reduction in immobility time in the forced swimming
      test may depend on memory impairment due to the drug's anticholinergic efficacy.
      Therefore, the present study evaluated learning and memory of the immobility
      response in rats after the pretest and test administrations of antidepressants
      having potent, comparatively lower, and no anticholinergic activities. Immobility
      was measured in the test session performed 24 h after the pretest session.
      Scopolamine and MK-801, which are agents that have memory impairing effects, were
      used as reference drugs for a better evaluation of the memory processes in the
      test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline
      (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and
      moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest
      administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased
      immobility time suggesting impaired "learning to be immobile" in the animals. The
      test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg),
      moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg)
      decreased immobility time, which suggested that the drugs exerted antidepressant
      activity or the animals did not recall that attempting to escape was futile. The
      test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg)
      produced no effect on immobility time. Even though the false-negative and
      positive responses made it somewhat difficult to interpret the findings, this
      study demonstrated that when given before the pretest antidepressants with or
      without anticholinergic activity seemed to be devoid of impairing the learning
      process in the test. 

PMID- 27037828
TI  - Wound healing modulation by a latex protein-containing polyvinyl alcohol
      biomembrane.
AB  - In a previous study, we performed the chemical characterization of a polyvinyl
      alcohol (PVA) membrane supplemented with latex proteins (LP) displaying wound
      healing activity, and its efficacy as a delivery system was demonstrated. Here,
      we report on aspects of the mechanism underlying the performance of the PVA-latex
      protein biomembrane on wound healing. LP-PVA, but not PVA, induced more intense
      leukocyte (neutrophil) migration and mast cell degranulation during the
      inflammatory phase of the cicatricial process. Likewise, LP-PVA induced an
      increase in key markers and mediators of the inflammatory response
      (myeloperoxidase activity, nitric oxide, TNF, and IL-1beta). These results
      demonstrated that LP-PVA significantly accelerates the early phase of the
      inflammatory process by upregulating cytokine release. This remarkable effect
      improves the subsequent phases of the healing process. The polyvinyl alcohol
      membrane was fully absorbed as an inert support while LP was shown to be active.
      It is therefore concluded that the LP-PVA is a suitable bioresource for
      biomedical engineering. 

PMID- 27037829
TI  - Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic
      effects on rod photoreceptor synapses via matrix-associated proteins.
AB  - Heterotrimeric G-proteins couple metabotropic receptors to downstream effectors.
      In retinal ON bipolar cells, Go couples the metabotropic receptor mGluR6 to the
      TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell. Light,
      via GTPase-activating proteins, deactivates Go , opens TRPM1 and depolarizes the
      cell. Go comprises Galphao1 , Gbeta3 and Ggamma13; all are necessary for
      efficient coupling. In addition, Gbeta3 contributes to trafficking of certain
      cascade proteins and to maintaining the synaptic structure. The goal of this
      study was to determine the role of Galphao1 in maintaining the cascade and
      synaptic integrity. Using mice lacking Galphao1 , we quantified the
      immunostaining of certain mGluR6-related components. Deleting Galphao1 greatly
      reduced staining for Gbeta3, Ggamma13, Gbeta5, RGS11, RGS7 and R9AP. Deletion of
      Galphao1 did not affect mGluR6, TRPM1 or PCP2. In addition, deleting Galphao1
      reduced the number of rod bipolar dendrites that invaginate the rod terminal,
      similar to the effect seen in the absence of mGluR6, Gbeta3 or the matrix
      associated proteins, pikachurin, dystroglycan and dystrophin, which are localized
      presynaptically to the rod bipolar cell. We therefore tested mice lacking mGluR6,
      Galphao1 and Gbeta3 for expression of these matrix-associated proteins. In all
      three genotypes, staining intensity for these proteins was lower than in wild
      type, suggesting a retrograde trans-synaptic effect. We propose that the mGluR6
      macromolecular complex is connected to the presynaptic rod terminal via a protein
      chain that includes the matrix-associated proteins. When a component of the
      macromolecular chain is missing, the chain may fall apart and loosen the
      dendritic tip adherence within the invagination.

PMID- 27037830
TI  - Controlled transurethral resection and incision of the bladder neck to treat
      female primary bladder neck obstruction: Description of a novel surgical
      procedure.
AB  - OBJECTIVES: To investigate the efficacy and complications of controlled
      transurethral resection and incision of the bladder neck to treat female primary
      bladder neck obstruction. METHODS: A total of 59 patients who were diagnosed with
      female primary bladder neck obstruction by urodynamic examination underwent
      surgical procedures at Urological Institute of the People's Liberation Army,
      First Affiliated Hospital of Third Military Medical University, Chongqing, China,
      between March 2010 and March 2014. For all patients, neurogenic, anatomical and
      dysfunctional voiding causes of bladder outlet obstruction had been excluded.
      Perioperative and follow-up data, including operative time, maximum urine flow
      rate, residual urine volume, International Prostate Symptom Score and Quality of
      Life Score, were prospectively investigated. RESULTS: All of the operations were
      completed uneventful. The median operative time was 15 +/- 8 min (range 10-22
      min). No massive hemorrhage or infection was reported. Follow-up data were
      available for 59, 59, and 57 of the patients at 1, 6 and 12 months
      postoperatively, respectively. The mean maximum urine flow rate increased from
      7.2 +/- 3.9 mL/s preoperatively to 26.1 +/- 5.2 mL/s postoperatively. The mean
      residual urine volume decreased from 162 +/- 75 to 20 +/- 7 mL. The mean
      International Prostate Symptom Score decreased from 24.5 +/- 7.2 to 5.5 +/- 3.6.
      The mean Quality of Life Score decreased from 5.4 +/- 1.7 to 1.9 +/- 1.1. All of
      the differences between the preoperative and postoperative values were
      significant (P < 0.001). CONCLUSIONS: The novel technique described here shortens
      the length of the urethra to 2.5 cm, which both released the obstruction and
      maintained continence. The results of the present preliminary study show that
      this method represents a safe and effective treatment for female primary bladder
      neck obstruction.

PMID- 27037831
TI  - Study of the Discrepancies between Crystallographic Porosity and Guest Access
      into Cadmium-Imidazolate Frameworks and Tunable Luminescence Properties by
      Incorporation of Lanthanides.
AB  - An extended member of the isoreticular family of metal-imidazolate framework
      structures, IFP-6 (IFP=imidazolate framework Potsdam), based on cadmium metal and
      an in situ functionalized 2-methylimidazolate-4-amide-5-imidate linker is
      reported. A porous 3D framework with 1D hexagonal channels with accessible pore
      windows of 0.52 nm has been synthesized by using an ionic liquid (IL) linker
      precursor. IFP-6 shows significant gas uptake capacity only for CO2 and CH4 at
      elevated pressure, whereas it does not adsorb N2 , H2 , and CH4 under atmospheric
      conditions. IFP-6 is assumed to deteriorate at the outside of the material during
      the activation process. This closing of the metal-organic framework (MOF) pores
      is proven by positron annihilation lifetime spectroscopy (PALS), which revealed
      inherent crystal defects. PALS results support the conservation of the inner
      pores of IFP-6. IFP-6 has also been successfully loaded with luminescent
      trivalent lanthanide ions (Ln(III) =Tb, Eu, and Sm) in a bottom-up one-pot
      reaction through the in situ generation of the linker ligand and in situ
      incorporation of photoluminescent Ln ions into the constituting network. The
      results of photoluminescence investigations and powder XRD provide evidence that
      the Ln ions are not doped as connectivity centers into the frameworks, but are
      instead located within the pores of the MOFs. Under UV light irradiation, Tb@IFP
      6 and Eu@IFP-6 (lambdaexc =365 nm) exhibit observable emission changes to a
      greenish and reddish color, respectively, as a result of strong Ln 4 f emissions.

PMID- 27037833
TI  - Molecular phylogeny of heterotrophic nitrifiers and aerobic denitrifiers and
      their potential role in ammonium removal.
AB  - To investigate the physiology and taxonomic composition of the key players of
      nitrification and denitrification processes in paddy fields, culture dependent
      and independent studies have been carried out. A total of 28 bacterial strains
      have been screened in which six were capable of reducing nitrate and nitrite as
      well as having significant ammonium removal potential. 16S rRNA-PCR-DGGE-based
      molecular typing of enriched batch culture was done with time duration to explore
      and identify dominant and stable soil denitrifiers. Notably, three isolates
      namely PDN3, PDN19, PDN14 were found to be efficiently involved in the removal of
      70.32, 71.46, and 81.50% of NH4 (+) and showed closest similarity (>98%) with
      Bacillus cereus, Bacillus subtilis, and Pseudomonas aeruginosa strains,
      respectively. The bacterial strain PDN14 showed maximum growth with highest
      ammonium removal rate (2.78 gN/(m(3) .h) has also been characterized based on
      nosZ gene which showed similarity to uncultured gamma- Proteobacteria, P.
      aeruginosa sp. B3. Median joining (MJ) network and rRNA secondary structure have
      been analyzed for their detailed taxonomic diversity and derived haplotype-based
      co-occurrence. Results demonstrated that such strains can serve as good candidate
      for in situ nitrogen transformation in paddy soils and improvingly characterized
      by physiological and detailed phylogenetic approaches. 

PMID- 27037832
TI  - Assembly of the draft genome of buckwheat and its applications in identifying
      agronomically useful genes.
AB  - Buckwheat (Fagopyrum esculentum Moench; 2n = 2x = 16) is a nutritionally dense
      annual crop widely grown in temperate zones. To accelerate molecular breeding
      programmes of this important crop, we generated a draft assembly of the buckwheat
      genome using short reads obtained by next-generation sequencing (NGS), and
      constructed the Buckwheat Genome DataBase. After assembling short reads, we
      determined 387,594 scaffolds as the draft genome sequence (FES_r1.0). The total
      length of FES_r1.0 was 1,177,687,305 bp, and the N50 of the scaffolds was 25,109
      bp. Gene prediction analysis revealed 286,768 coding sequences (CDSs;
      FES_r1.0_cds) including those related to transposable elements. The total length
      of FES_r1.0_cds was 212,917,911 bp, and the N50 was 1,101 bp. Of these, the
      functions of 35,816 CDSs excluding those for transposable elements were annotated
      by BLAST analysis. To demonstrate the utility of the database, we conducted
      several test analyses using BLAST and keyword searches. Furthermore, we used the
      draft genome as a reference sequence for NGS-based markers, and successfully
      identified novel candidate genes controlling heteromorphic self-incompatibility
      of buckwheat. The database and draft genome sequence provide a valuable resource
      that can be used in efforts to develop buckwheat cultivars with superior
      agronomic traits. 

PMID- 27037834
TI  - Arterial oxygen saturation and heart rate after birth in newborns with and
      without maternal bonding.
AB  - BACKGROUND: The aim of this study was to determine and compare changes in
      arterial oxygen saturation (SpO2 ) and heart rate (HR) in healthy term infants
      with and without maternal bonding. METHOD: This was a prospective observational
      study in healthy term infants. SpO2 and HR were recorded from 1 to 10 min after
      birth. After this, SpO2 and HR were registered at 15, 30 and 60 min and then at
      12 and 24 h after birth. SpO2 and HR were measured with a pulse oximeter.
      RESULTS: A total of 216 healthy term infants were divided into three different
      groups: 136 (63%) born by vaginal delivery, 56 (26%) born by cesarean section
      with bonding, and 24 (11%) born by cesarean section without bonding. No
      difference in SpO2 was found in babies born by cesarean section with or without
      maternal bonding. In neonates delivered vaginally, SpO2 was significantly higher
      during the first 10 min after birth than in neonates born by cesarean section
      with bonding (P < 0.05). Compared with infants born by cesarean section without
      bonding, this tendency was not significant. In general, HR was similar across
      groups, although, for infants born by cesarean section, neonates who received
      bonding had lower HR from 6 to 8 min (P < 0.05). CONCLUSIONS: In healthy term
      newborns, maternal bonding in infants born by cesarean section did not have
      effects on SpO2 . Some differences were observed in HR between infants born by
      cesarean section with and without bonding.

PMID- 27037835
TI  - AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid
      carcinoma.
AB  - Thyroid cancer is the fastest increasing cancer worldwide in all age groups.
      Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in
      both adults and children. PTC genomic landscape has been extensively studied in
      adults, but information regarding sporadic pediatric patients is lacking.
      Although BRAF V600E mutation is highly prevalent in adults, this mutation is
      uncommon in pediatric cases. As adult and pediatric PTC is a mitogen-activated
      protein kinase-driven cancer, this altered pathway might be activated by
      different genetic events. The aim of this study was to investigate the occurrence
      of AGK-BRAF fusion gene, recently described in radiation-exposed pediatric PTC,
      in a cohort of exclusively sporadic pediatric PTC. The series consisted of 30
      pediatric PTC younger than 18 years of age at the time of diagnosis and 15
      matched lymph node metastases (LNM). Primary tumors and matched LNM were screened
      for the presence of the AGK-BRAF fusion transcript by RT-PCR. To confirm the
      identity of the amplified products, randomly selected samples positive for the
      presence of the fusion transcripts were sequenced. Moreover, BRAF dual-color,
      break-apart probes confirmed BRAF rearrangement. Overall, the AGK-BRAF fusion
      gene was detected in 10% (3/30) of primary tumors. For one of these cases, paired
      LNM was also available, which also shows the presence of AGK-BRAF fusion gene.
      This study described, for the first time, the presence of AGK-BRAF in sporadic
      pediatric PTC. Understanding the molecular events underlying pediatric PTC may
      improve preoperative diagnosis, allow molecular prognostication and define a
      therapeutic approach toward sporadic PTC patients.

PMID- 27037836
TI  - LORAKS makes better SENSE: Phase-constrained partial fourier SENSE reconstruction
      without phase calibration.
AB  - PURPOSE: Parallel imaging and partial Fourier acquisition are two classical
      approaches for accelerated MRI. Methods that combine these approaches often rely
      on prior knowledge of the image phase, but the need to obtain this prior
      information can place practical restrictions on the data acquisition strategy. In
      this work, we propose and evaluate SENSE-LORAKS, which enables combined parallel
      imaging and partial Fourier reconstruction without requiring prior phase
      information. THEORY AND METHODS: The proposed formulation is based on combining
      the classical SENSE model for parallel imaging data with the more recent LORAKS
      framework for MR image reconstruction using low-rank matrix modeling. Previous
      LORAKS-based methods have successfully enabled calibrationless partial Fourier
      parallel MRI reconstruction, but have been most successful with nonuniform
      sampling strategies that may be hard to implement for certain applications. By
      combining LORAKS with SENSE, we enable highly accelerated partial Fourier MRI
      reconstruction for a broader range of sampling trajectories, including widely
      used calibrationless uniformly undersampled trajectories. RESULTS: Our empirical
      results with retrospectively undersampled datasets indicate that when SENSE
      LORAKS reconstruction is combined with an appropriate k-space sampling
      trajectory, it can provide substantially better image quality at high
      acceleration rates relative to existing state-of-the-art reconstruction
      approaches. CONCLUSION: The SENSE-LORAKS framework provides promising new
      opportunities for highly accelerated MRI. Magn Reson Med 77:1021-1035, 2017. (c)
      2016 International Society for Magnetic Resonance in Medicine.

PMID- 27037837
TI  - Combined liver-thoracic transplantation: single-center experience with
      introduction of the 'Liver-first' principle.
AB  - Combined liver/thoracic transplantation (cLiThTx) is a complex procedure for end
      stage/advanced liver and heart(H)/lung(Lu) disease. To avoid futile use of
      multiple organs in single recipients, results should be scrutinously analyzed.
      Single-center cLiThTx (04/2000-12/2015) were reviewed for the following:
      demographics, indications, surgical technique, complications, rejection, and five
      year patient survival. Results are reported as median (range). Fourteen
      consecutive patients underwent cLiThTx: 3 cLiHTx, 10 cLiLuTx, and 1 cLiHLuTx.
      Recipient age was 42 years (17-63 years). Most frequent indications were cystic
      fibrosis (n = 5), hepatopulmonary fibrosis (n = 2), amyloidosis (n = 2), and
      epithelioid hemangio-endothelioma (n = 2). Thoracic organs were transplanted
      first, except in three where LiTx preceded LuTx. In the latter, lungs were
      preserved by normothermic ex vivo lung perfusion. Stenting was performed for
      stenosis of bile duct (n = 4), hepatic artery (n = 2), and bronchus (n = 2).
      Abdominal interventions were required for bleeding (n = 3), evisceration (n = 1),
      and adhesiolysis (n = 1). One liver (cLiLuTx) was lost to hepatic artery
      thrombosis 3 months post-transplant and successfully retransplanted. One patient
      (cLiHTx) died 4 months post-transplant (myocardial infarction). Follow-up was 4
      years (2 months-16 years). One liver and 5 pulmonary rejections occurred, all
      mild and reversible. Two patients developed bronchiolitis obliterans, one is
      clinically well 16 years post-transplant, and the other successfully
      retransplanted. Estimated 5-year patient survival is 90%. CLiThTx is safe with
      excellent short-/long-term surgical and immunological results. 

PMID- 27037838
TI  - Competition and quality in a physiotherapy market with fixed prices.
AB  - Our study focuses on competition and quality in physiotherapy organized and
      regulated by the Social Insurance Institution of Finland (Kela). We first derive
      a hypothesis with a theoretical model and then perform empirical analyses of the
      data. Within the physiotherapy market, prices are regulated by Kela, and after
      registration eligible firms are accepted to join a pool of firms from which
      patients choose service providers based on their individual preferences. By using
      2SLS estimation techniques, we analyzed the relationship among quality,
      competition and regulated price. According to the results, competition has a
      statistically significant (yet weak) negative effect (p = 0.019) on quality. The
      outcome for quality is likely caused by imperfect information. It seems that Kela
      has provided too little information for patients about the quality of the
      service.

PMID- 27037839
TI  - Hepatic resection of non-colorectal non-endocrine liver metastases.
AB  - BACKGROUND: Hepatic resection is standard treatment for liver metastases from
      colorectal and neuroendocrine cancers as well as primary biliary and hepatic
      carcinomas. The role of hepatic resection in patients with non-colorectal non
      endocrine liver metastases (NCNELM) is less defined. Overall survival in this
      group of patients is poor with few patients surviving beyond two years, even with
      modern chemotherapy. METHODS: A prospective database of all liver resections
      performed by a single surgeon (KSH) from January 2007 to December 2014 was
      maintained. Patient demographics, surgical and pathological data were collected
      prospectively; survival data were updated retrospectively. Patients were grouped
      according to pathology and analysis was performed using SPSS (version 21).
      RESULTS: A total of 48 patients underwent hepatic resection for NCNELM, of which
      18 were major resections. Pathologies encountered included sarcoma in 8/48, both
      breast and ovarian in 6/48 each and renal cell carcinoma and melanoma, each
      representing 5/48. A result of 38/48 patients undertook chemotherapy prior to
      surgery. R0 margin was achieved in 96%. Seven patients suffered complications
      from surgery and one peri-operative mortality. Overall survival at 1, 3 and 5
      years was 93%, 83% and 61%, respectively. Forty-four percent of patients
      developed disease recurrence, 29% at distant sites. CONCLUSION: Hepatic resection
      can be achieved safely for NCNELM. Patient selection is key, along with a
      standardized surgical and anaesthetic technique. Patients should be rigorously
      investigated to exclude disseminated disease and multidisciplinary discussion
      must take place prior to surgery. Patients with NCNELM should not routinely be
      excluded from liver resection and selected patients may benefit from resection.

PMID- 27037840
TI  - Epidemiology and clinical relevance of mutations in postpolycythemia vera and
      postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM
      group.
AB  - Transformation to secondary myelofibrosis (MF) occurs as part of the natural
      history of polycythemia vera (PPV-MF) and essential thrombocythemia (PET-MF).
      Although primary (PMF) and secondary MF are considered similar diseases and
      managed similarly, there are few studies specifically focused on the latter. The
      aim of this study was to characterize the mutation landscape, and describe the
      main clinical correlates and prognostic implications of mutations, in a series of
      359 patients with PPV-MF and PET-MF. Compared with PV and ET, the JAK2V617F and
      CALR mutated allele burden was significantly higher in PPV-MF and/or PET-MF,
      indicating a role for accumulation of mutated alleles in the process of
      transformation to MF. However, neither the allele burden nor the type of driver
      mutation influenced overall survival (OS), while absence of any driver mutation
      (triple negativity) was associated with significant reduction of OS in PET-MF,
      similar to PMF. Of the five interrogated subclonal mutations (ASXL1, EZH2, SRSF2,
      IDH1, and IDH2), that comprise a prognostically detrimental high molecular risk
      (HMR) category in PMF, only SRSF2 mutations were associated with reduced survival
      in PET-MF, and no additional mutation profile with prognostic relevance was
      highlighted. Overall, these data indicate that the molecular landscape of
      secondary forms of MF is different from PMF, suggesting that unknown mutational
      events might contribute to the progression from chronic phase disease to
      myelofibrosis. These findings also support more extended genotyping approaches
      aimed at identifying novel molecular abnormalities with prognostic relevance for
      patients with PPV-MF and PET-MF. Am. J. Hematol. 91:681-686, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27037841
TI  - Aberrant O-GlcNAcylation disrupts GNE enzyme activity in GNE myopathy.
AB  - UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key
      enzyme for the biosynthesis of sialic acids. Sialic acids are terminal
      monosaccharides of glycoconjugates and gangliosides, which have an essential
      influence on various cell interactions. The sialylation of proteins varies during
      development, aging, and pathogenesis of degenerative diseases such as Morbus
      Alzheimer, diabetes mellitus type II, or myopathies. Mutation of methionine 743
      in the GNE leads to a 30% reduction of the enzyme activity and is responsible for
      an aggressive form of GNE myopathy. GNE myopathy or hereditary inclusion body
      myopathy (HIBM) is an age-dependent muscular dystrophy. Here, we analyzed the
      impact of the exchange of methionine to threonine at position 743 which
      introduces an additional potential phosphorylation/O-GlcNAcylation site. We found
      increased O-GlcNAcylation of the M743T variant compared to the wild-type GNE. In
      addition, removal of the O-GlcNAc of the M743T variant resulted in an increased
      activity comparable to activity of the wild-type GNE. Furthermore, the half-life
      of the M743T variant is two times longer than for the wild-type GNE protein. This
      study provides that the balance of phosphorylation and O-GlcNAcylation is
      decisive involved in efficiency and regulation of GNE.

PMID- 27037842
TI  - Induction of antigen-specific TH 9 immunity accompanied by mast cell activation
      blocks tumor cell engraftment.
AB  - The engraftment of circulating cancer cells at distal sites represents a key step
      in the metastatic cascade, yet remains an unexplored target for therapeutic
      intervention. In this study, we establish that a vaccination strategy yielding an
      antigen-specific TH 9 response induces long term host surveillance and prevents
      the engraftment of circulating cancer cells. Specifically, we show that
      vaccination with a recombinant CEA IgV-like N domain, formulated with the TLR3
      ligand poly I:C, elicits a CEA-specific TH 9 response, wherein IL-9 secreting TH
      cells act in concert with CEA N domain-specific antibodies as well as activated
      mast cells in preventing tumor cell engraftment. The development of this immune
      response was dependent on TLR3, since interference with the TLR3-dsRNA complex
      formation led to a reduction in vaccine-imparted protection and a shift in the
      resulting immune response toward a TH 2 response. These findings point to the
      existence of an alternate tumor targeting immune mechanism that can be exploited
      for the purpose of developing vaccine therapies targeting tumor dissemination and
      engraftment.

PMID- 27037843
TI  - The Objective and Subjective Caregiving Burden and Caregiving Behaviours of
      Parents of Adolescents with Anorexia Nervosa.
AB  - OBJECTIVE: The study aimed to examine caregiving burden and levels of distress,
      accommodating behaviours, expressed emotion (EE) and carers' skills, in parents
      of adolescents with anorexia nervosa. METHOD: A semi-structured interview
      assessed the objective burden (time spent across caregiving tasks) in parents (n
      = 196) of adolescents (n = 144) receiving outpatient treatment for anorexia
      nervosa. Subjective burden (carers' distress), accommodating behaviours, EE and
      carers' skills were measured by self-report. RESULTS: Mothers, on average, spent
      2.5 h/day of care, mainly providing food and emotional support, compared with 1
      h/day by fathers. The level of distress and accommodating behaviour was
      significantly lower in fathers than in mothers. Accommodating behaviours mediated
      the relationship between objective burden and subjective burden in mothers,
      whereas EE and carers' skills did not mediate this relationship for either
      parent. DISCUSSION: The objective burden for most mothers is high. In order to
      reduce subjective burden, it may be helpful to target accommodating behaviours.
      TRIAL REGISTRATION: ISRCTN83003225 - Expert Carers Helping Others (ECHO).
      Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 27037844
TI  - Rationale and design for an investigation to optimize selective serotonin
      reuptake inhibitor treatment for pregnant women with depression.
AB  - The physiological changes of pregnancy can affect the pharmacokinetics of a drug,
      thereby affecting its dose requirements. Because pharmacokinetic (PK) studies in
      pregnant women have rarely been conducted, evidence-based dosing adjustments are
      seldom available. In particular, despite the fact that the use of antidepressants
      has become increasingly common, pregnancy-associated PK changes of the selective
      serotonin reuptake inhibitors (SSRIs) are largely unknown.

PMID- 27037845
TI  - Ligand-Free, Cu- and Fe-Catalyzed Selective Ring-Opening Arylations of
      Benzoxazoles with Aryl Iodides.
AB  - Cu- or Fe-based catalyst systems have been reported to selectively catalyze the
      N,N-diarylation or N-monoarylation of benzoxazoles ring-opening with aryl iodides
      in the absence of additional added ligand in polyethylene glycol under an inert
      atmosphere. Two types of coupling products (triphenylamines and diphenylamines)
      have been examined and the reaction routes can be simply controlled by changing
      the metal salts (Cu or Fe) as catalyst. A range of substrates have been
      investigated for the diverse reactions, and the corresponding arylation products
      were achieved in good to high yields. This selective, low-cost, and
      environmentally friendly protocol displays great potential for replacing existing
      methodologies as well as extending the synthetic applications of benzoxazoles.

PMID- 27037846
TI  - Guideline of guidelines: thromboprophylaxis for urological surgery.
AB  - Decisions regarding thromboprophylaxis in urologic surgery involve a trade-off
      between decreased risk of venous thromboembolism (VTE) and increased risk of
      bleeding. Both patient- and procedure-specific factors are critical in making an
      informed decision on the use of thromboprophylaxis. Our systematic review of the
      literature revealed that existing guidelines in urology are limited.
      Recommendations from national and international guidelines often conflict and are
      largely based on indirect as opposed to procedure-specific evidence. These issues
      have likely contributed to large variation in the use of VTE prophylaxis within
      and between countries. The majority of existing guidelines typically suggest
      prolonged thromboprophylaxis for high-risk abdominal or pelvic surgery, without
      clear clarification of what these procedures are, for up to 4 weeks post
      discharge. Existing guidance may result in the under-treatment of procedures with
      low risk of bleeding and the over-treatment of oncological procedures with low
      risk of VTE. Guidance for patients who are already anticoagulated are not
      specific to urological procedures but generally involve evaluating patient and
      surgical risks when deciding on bridging therapy. The European Association of
      Urology Guidelines Office has commissioned an ad hoc guideline panel that will
      present a formal thromboprophylaxis guideline for specific urological procedures
      and patient risk factors. 

PMID- 27037847
TI  - Multiplexed Imaging of Protein Phosphorylation on Membranes Based on Ti(IV)
      Functionalized Nanopolymers.
AB  - Accurate protein phosphorylation analysis reveals dynamic cellular signaling
      events not evident from protein expression levels. The most dominant biochemical
      assay, western blotting, suffers from the inadequate availability and poor
      quality of phospho-specific antibodies for phosphorylated proteins. Furthermore,
      multiplexed assays based on antibodies are limited by steric interference between
      the antibodies. Here we introduce a multifunctionalized nanopolymer for the
      universal detection of phosphoproteins that, in combination with regular
      antibodies, allows multiplexed imaging and accurate determination of protein
      phosphorylation on membranes.

PMID- 27037848
TI  - Abortion Stigma: A Systematic Review.
AB  - CONTEXT: Although stigma has been identified as a potential risk factor for the
      well-being of women who have had abortions, little attention has been paid to the
      study of abortion-related stigma. METHODS: A systematic search of the databases
      Medline, PsycArticles, PsycInfo, PubMed and Web of Science was conducted; the
      search terms were "(abortion OR pregnancy termination) AND stigma* ." Articles
      were eligible for inclusion if the main research question addressed experiences
      of individuals subjected to abortion stigma, public attitudes that stigmatize
      women who have had abortions or interventions aimed at managing abortion stigma.
      To provide a comprehensive overview of this issue, any study published by
      February 2015 was considered. The search was restricted to English- and German
      language studies. RESULTS: Seven quantitative and seven qualitative studies were
      eligible for inclusion. All but two dated from 2009 or later; the earliest was
      from 1984. Studies were based mainly on U.S. samples; some included participants
      from Ghana, Great Britain, Mexico, Nigeria, Pakistan, Peru and Zambia. The
      majority of studies showed that women who have had abortions experience fear of
      social judgment, self-judgment and a need for secrecy. Secrecy was associated
      with increased psychological distress and social isolation. Some studies found
      stigmatizing attitudes in the public. Stigma appeared to be salient in abortion
      providers' lives. Evidence of interventions to reduce abortion stigma was scarce.
      Most studies had limitations regarding generalizability and validity. CONCLUSION:
      More research, using validated measures, is needed to enhance understanding of
      abortion stigma and thereby reduce its impact on affected individuals.

PMID- 27037849
TI  - The clinical diagnostic value of target biopsy using narrow-band imaging
      endoscopy and accurate laryngeal carcinoma pathologic specimen acquisition.
AB  - OBJECTIVE: To estimate the clinical significance of target biopsy for clinical
      diagnosis and determine accurate laryngeal lesion pathologic specimen acquisition
      via narrow-band imaging (NBI) endoscopy. METHODS: A total of 138 samples from
      patients with laryngeal lesions (carcinoma, 118; hyperplasia, 3; mild dysplasia,
      2; moderate dysplasia, 5; severe dysplasia, 5; vocal cord polyp, 1; and
      inflammatory lesion, 4) were collected from the Department of Otolaryngology Head
      and Neck Surgery of Tianjin Union Medical Center from 1 January 2013 to 1
      February 2015. All patients were divided into the regular biopsy and NBI target
      biopsy groups; the imaging data were recorded and patient samples were biopsied.
      Pathologic diagnoses were used to evaluate the accuracies of regular and target
      biopsy. RESULTS: Based on the pathologic diagnosis, NBI target pathology yielded
      an accurate laryngeal lesion pathologic specimen acquisition rate of 95.6%
      (65/68), significantly higher than that yielded by regular biopsy (75.7%, 53/70;
      chi2 = 10.99, P = 0.001). In the NBI target pathology group, the correct accurate
      pathologic specimen acquisition rates at laryngeal cancer diagnostic stages 0
      (Tis), I and II were 100%, 100% and 85.71%, respectively, which were higher than
      the corresponding rates in the regular biopsy group (0%, chi2 = 10.000, P =
      0.002; 25%, chi2 = 5.625, P = 0.018; and 38.46%, chi2 = 6.454, P = 0.011,
      respectively). CONCLUSIONS: In cases of laryngeal carcinoma, NBI endoscopy plays
      an important role in clinical diagnosis and accurate pathologic specimen
      acquisition and could be a regular clinical method for laryngeal lesion
      detection.

PMID- 27037850
TI  - Plasma cells with segmented nuclei in benign lymph node follicular hyperplasia.

PMID- 27037851
TI  - Targeted DNA delivery to cancer cells using a biotinylated chitosan carrier.
AB  - A novel biotinylated chitosan-graft-polyethyleneimine (Bio-Chi-g-PEI) copolymer
      was synthesized and evaluated as a nonviral gene delivery carrier for improvement
      of the transfection efficiency, endosomal escape, and targeted gene delivery of a
      plasmid encoding green fluorescent protein N1 (pEGFP-N1) into two different
      biotin-overexpressing cell lines including HeLa and OVCAR-3 cells. The structure
      of the obtained copolymers was confirmed by 1 H nuclear magnetic resonance (1 H
      NMR) and Fourier transform infrared spectroscopy. Physicochemical properties of
      the Bio-Chi-g-PEI/plasmid DNA (pDNA) complexes such as complex stability, size,
      zeta potential, and their morphology were investigated at various weight ratios
      of copolymer to pDNA. Bio-Chi-g-PEI copolymers could effectively condense pDNA
      into small particles with average diameters less than 164 nm and the zeta
      potential of +34.8 mV at the N/P ratio of 40/1. As revealed by flow cytometry,
      Bio-Chi-g-PEI/pDNA complexes had lower cytotoxicity than that of PEI 25 kDa/pDNA
      complexes in both cell lines. In vitro experiments revealed that the Bio-Chi
      gPEI/pDNA complexes not only had much lower cytotoxicity, but also displayed
      higher transfection efficiency than that of PEI 25kDa/pDNA complexes. High
      percentage of cancer cells was successfully transfected by Bio-Chi-g-PEI/pDNA and
      properly expressed GFP protein. This study indicates that this copolymer complex
      can be a promising gene delivery carrier.

PMID- 27037852
TI  - Two drugs are better than one ... for a while. Duration of dual-antiplatelet
      therapy following stroke or transient ischaemic attack.

PMID- 27037853
TI  - Relapsed or Refractory Lymphoblastic Lymphoma in Children: Results and Analysis
      of 23 Patients in the EORTC 58951 and the LMT96 Protocols.
AB  - BACKGROUND: The treatment of children with T-cell lymphoblastic lymphoma (T-LBL)
      and precursor B-cell lymphoblastic lymphoma (pB-LBL) has improved during the last
      decades. However, patients with relapsed or refractory lymphomas still have a
      poor prognosis. METHODS: We report the characteristics and evolution of T-LBL and
      pB-LBL relapses in two multicenter prospective studies (LMT 96, European
      Organization for Research and Treatment of Cancer 58951). RESULTS: From 1997 to
      2008, 194 patients were included in these studies (157 T-LBL; 37 pB-LBL); among
      them, 23 patients underwent relapse or progression (18 T-LBL and 5 pB-LBL). The
      median age was 7.7 years (range 1.4-16.3). The survival rate at 8 years was 8.7%
      (21 deaths). The median time from diagnosis to relapse was 9 months [1-69] and 11
      months [1-45] for T-LBL and pB-LBL, respectively. Twenty-two patients received a
      second-line treatment but remission was achieved in only seven patients. In 10
      patients, intensification with hematopoietic stem cell transplantation (HSCT) was
      performed and four of them had a second relapse. Two patients still alive had T
      LBL, experienced relapses 15 and 69 months after diagnosis, and received HSCT.
      Relapse during the intensive phase and second-line treatment without HSCT were
      identified as risk factors for bad prognosis (P = 0.01). CONCLUSIONS: The results
      of second-line treatment, including intensive chemotherapy and HSCT, show that
      salvage treatment is still disappointing in controlling refractory forms. Early
      identification of patients at high risk of relapse is mandatory, allowing earlier
      intensification. Valid prognostic parameters, such as biological markers, are
      needed. International cooperation is warranted to collect more data on these rare
      diagnoses.

PMID- 27037854
TI  - Predicting long-term bleeding after percutaneous coronary intervention.
AB  - OBJECTIVES: To construct a model to predict long-term bleeding events following
      percutaneous coronary intervention (PCI). BACKGROUND: Treatment with dual
      antiplatelet therapy following PCI involves balancing the benefits of preventing
      ischemic events with the risks of bleeding. There are no models to predict long
      term bleeding events after PCI. METHODS: We analyzed 1-year bleeding outcomes
      from 3,128 PCI procedures in the Patient Risk Information Services Manager
      (PRISM) observational study. Patient-reported bleeding events were categorized
      according to Bleeding Academic Research Consortium (BARC) definitions. Logistic
      regression analysis was used to develop a model predicting BARC >= 1 bleeding.
      RESULTS: BARC 0, 1, 2 or 3 bleeding was observed in 574 (18.4%); 2382 (76.2%);
      114 (3.6%); and 58 (1.8%) patients, respectively. Compared to patients who had no
      bleeding, patients with BARC >= 1 bleeding were more often female (30 vs. 23%),
      Caucasian (94 vs. 83%), had a higher incidence of drug eluting stent (DES)
      implantation (83 vs. 76%) and warfarin therapy (7.4 vs. 3.9%), and a lower
      incidence of diabetes (31 vs. 45%; P-value <0.01 for all comparisons). A 27
      variable model had moderate discrimination (c-statistic of 0.674), and good
      calibration, as did a parsimonious model with 10 variables (c-statistic = 0.667).
      This model performed well in predicting BARC >= 2 bleeding events as well (c
      statistic = 0.653). CONCLUSIONS: Bleeding is common in the first year after PCI,
      and can be predicted by pre-procedural patient characteristics and use of DES.
      Objective estimates of bleeding risk may help support shared decision-making with
      respect to stent selection and duration of antiplatelet therapy following PCI.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27037855
TI  - Basset Hound thrombopathia in a 4-month-old female Ba-Shar (Sharp Asset).
AB  - A 3-month-old female Basset Hound-Shar Pei mix puppy (Ba-Shar or Sharp Asset)
      presented with oral bleeding due to a cracked molar. On physical exam, an aural
      hematoma was also noted that the owner indicated was chronic. The puppy was
      hospitalized for over 24 h until the bleeding was brought under control. At 4
      months of age, the puppy again presented with oral bleeding due to loss of
      deciduous teeth and was hospitalized until bleeding was controlled. Coagulation
      screening tests, platelet numbers, and von Willebrand Factor antigen levels were
      within reference limits. Based on the presence of platelet-type bleeding in the
      face of normal screening test results, samples were submitted for DNA testing for
      Basset Hound thrombopathia. The puppy tested as affected for the calcium and
      diacylglycerol regulated guanine nucleotide exchange factor I (CalDAG-GEFI)
      mutation causing this disorder. This is the first time thrombopathia has been
      diagnosed in a "designer" breed.

PMID- 27037856
TI  - Urethral bulking for recurrent stress urinary incontinence after midurethral
      sling failure.
AB  - AIMS: To assess the effectiveness of a polyacrylamide hydrogel (PAHG;
      Bulkamid(r)) in treating recurrent stress urinary incontinence (SUI) following a
      previous midurethral sling (MUS) implant. METHODS: This observational study,
      conducted since 2009, included 60 patients with recurrent SUI or mixed urinary
      incontinence (MUI) after a previous MUS and who chose to be treated with PAHG.
      Objective and subjective outcomes were assessed at 1, 6, and 12 months after the
      initial injection. Patients were classified as cured based on a negative cough
      test (supine and standing) and <2 g urine on 1-hr pad test and a VAS score
      improved by >=90%. Improved were those with the loss of only a few drops of urine
      during the cough test and 2-10 g urine on 1-hr pad test or a reduction >50%
      compared with preoperative urine loss and a VAS score improved by >=75%. RESULTS:
      The volume of PAHG injected in the current study ranged from 1-3 ml.
      Cured/improved rates were 93.3% (56/60), 88.3% (53/60), and 83.6% (46/55) at 1,
      6, and 12 months, respectively. Patients with MUI had a cured urgency urinary
      incontinence rate of 36.8%, 47.4%, and 38.9%, respectively. Voiding dysfunction
      rates were 13.3% (8/60), 8.3% (5/60), and 1.8% (1/55) at 1, 6, and 12 months and
      urinary tract infection rates were 5% (3/60), 11.7% (7/60), and 3.6% (2/55),
      respectively. Other adverse events were short-term and/or observed in <4% of
      patients. CONCLUSIONS: PAHG can be used to treat recurrent SUI after MUS failure
      with good outcome and low complication rates. Neurourol. Urodynam. 36:722-726,
      2017. (c) 2016 The Authors. Neurourology and Urodynamics published by Wiley
      Periodicals, Inc.

PMID- 27037857
TI  - An oxidative burst and its attenuation by bacterial peroxidase activity is
      required for optimal establishment of the Arachis hypogaea-Bradyrhizobium sp.
      symbiosis.
AB  - AIMS: The main purpose of this study was to determine whether the Arachis
      hypogaea L. root oxidative burst, produced at early stages of its symbiotic
      interaction with Bradyrhizobium sp. SEMIA 6144, and the bacterial antioxidant
      system are required for the successful development of this interaction. METHODS
      AND RESULTS: Pharmacological approaches were used to reduce both plant oxidative
      burst and bacterial peroxidase enzyme activity. In plants whose H2 O2 levels were
      decreased, a low nodule number, a reduction in the proportion of red nodules (%)
      and an increase in the bacteroid density were found. The symbiotic phenotype of
      plants inoculated with a Bradyrhizobium sp. SEMIA 6144 culture showing decreased
      peroxidase activity was also affected, since the biomass production, nodule
      number and percentage of red nodules in these plants were lower than in plants
      inoculated with Bradyrhizobium sp. control cultures. CONCLUSIONS: We demonstrated
      for the first time that the oxidative burst triggered at the early events of the
      symbiotic interaction in peanut, is a prerequisite for the efficient development
      of root nodules, and that the antioxidant system of bradyrhizobial peanut
      symbionts, particularly the activity of peroxidases, is counteracting this
      oxidative burst for the successful establishment of the symbiosis. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Our results provide new insights into the mechanisms
      involved in the development of the symbiotic interaction established in A.
      hypogaea L. a legume infected in an intercellular way.

PMID- 27037858
TI  - Influence of platelet and white blood cell counts on major thrombosis - analysis
      from a patient registry in essential thrombocythemia.
AB  - OBJECTIVES: Although guidelines recommend normalization of platelet counts as an
      appropriate endpoint for treatment in high-risk essential thrombocythemia (ET),
      retrospective studies could not prove a correlation of diagnostic platelet counts
      with an increased thrombotic rate. There is, however, an increasing evidence that
      leukocytosis is an important risk factor for arterial thrombosis in
      myeloproliferative neoplasms. METHODS: This study considers the Austrian cohort
      of a European registry regarding the platelet-lowering therapeutic anagrelide.
      Influence of platelet and white blood cell (WBC) counts on thrombotic risk was
      assessed. RESULTS: Using the calculated cutoffs of 574.5 G/L for platelets and
      8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a
      clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on
      the occurrence of major thrombotic events. The time to a major thrombotic event
      was shortest (P < 0.001) and the frequency related to 100 patient-years was
      highest (P = <0.001) when both platelet and WBC counts ranged above the
      calculated cutoffs. CONCLUSION: Our data add evidence to the impact of platelet
      and WBC counts on thrombosis in ET. We suspect a particular interaction between
      platelets and WBC which might be based on a biological interplay depending on
      particular cell counts.

PMID- 27037859
TI  - Dissecting the voice: Health professions students' perceptions of instructor age
      and gender in an online environment and the impact on evaluations for faculty.
AB  - Gender and age bias is well-documented in academia with many studies
      demonstrating bias in students' evaluations of instructors. Failure of an
      instructor to meet gender or age-based expectations can translate to lower scores
      or negative comments on evaluations. While there is some evidence of bias in
      students' evaluations of online instructors, current studies have not fully
      examined the relationship between bias and instructor vocal characteristics.
      First-year dental students at two institutions were randomly assigned one of four
      videos on spinal cord anatomy to view. Videos contained identical content but
      were narrated by individuals of different gender and age (younger man, younger
      woman, older man, older woman). Students completed a content-based prequiz,
      watched the video, completed a postquiz, and answered a questionnaire evaluating
      the video and instructor. Students at Institution A rated the younger man and
      younger woman highest for nearly every evaluation category. At Institution B
      students rated the older man and younger woman highest. Results reveal that the
      older woman's voice received the lowest rankings for nearly every question in
      both samples. This report confirms the presence of gender and age bias in student
      evaluations of instructors in an online environment and demonstrates that bias
      may surface in response to vocal characteristics. Bias may impact older women
      more significantly than other groups. Differences in results from Institution A
      and Institution B suggest that factors affecting student perceptions of
      instructors, and the roles that gender and age bias may play in student
      evaluations, are complex and may be contextual. Anat Sci Educ 9: 537-544. (c)
      2016 American Association of Anatomists.

PMID- 27037860
TI  - Phenotypic heterogeneity in PIK3CA-related overgrowth spectrum.

PMID- 27037861
TI  - Gadolinium-Decorated Silica Microspheres as Redox-Responsive MRI Probes for
      Applications in Cell Therapy Follow-Up.
AB  - The redox microenvironment within a cell graft can be considered as an indicator
      to assess whether the graft is metabolically active or hypoxic. We present a
      redox-responsive MRI probe based on porous silica microparticles whose surface
      has been decorated with a Gd-chelate through a disulphide bridge. Such
      microparticles are designed to be interspersed with therapeutic cells within a
      biocompatible hydrogel. The onset of reducing conditions within the hydrogel is
      paralleled by an increased clearance of Gd, that can be detected by MRI.

PMID- 27037862
TI  - Microarray and genetic analysis reveals that csa-miR159b plays a critical role in
      abscisic acid-mediated heat tolerance in grafted cucumber plants.
AB  - Root-shoot communication plays a vital role in plant growth, development and
      adaptation to environmental stimuli. Grafting-induced stress tolerance is
      associated with the induction of plentiful stress-related genes and proteins; the
      mechanism involved, however, remains obscure. Here, we show that the enhanced
      tolerance against heat stress in cucumber plants with luffa as rootstock was
      accompanied with an increased accumulation of abscisic acid (ABA), down
      regulation of a subset of microRNAs (miRNAs) but up-regulation of their target
      genes and CsHSP70 accumulation in the shoots. Significantly, luffa rootstock and
      foliar application of ABA both down-regulated csa-miR159b and up-regulated its
      target mRNAs CsGAMYB1 and CsMYB29-like and CsHSP70 accumulation in cucumber,
      while ectopic expression of csa-miR159b led to decreased heat tolerance, AtMYB33
      transcript and AtHSP70 accumulation in Arabidopsis plants. Taken together, our
      results suggest that root-originated signals such as ABA could alter miRNAs in
      the shoots, which have a major role in the post-transcriptional regulation of the
      stress-responsive genes.

PMID- 27037863
TI  - Seizure outcome following medical treatment of mesial temporal lobe epilepsy:
      Clinical phenotypes and prognostic factors.
AB  - OBJECTIVE: Surveys on mesial temporal lobe epilepsy (MTLE) repeatedly demonstrate
      that seizures are commonly resistant to antiepileptic drugs (AED), but patients
      usually came from third-level epilepsy centers, making the medically refractory
      population larger. The aim of our study is to evaluate patterns of seizure
      control and prognostic factors of general population of MTLE patients observed in
      clinical practice. METHODS: Sixty five MTLE patients were evaluated for
      demographic data, family history, febrile convulsions, detailed descriptions of
      auras and seizures, presence of secondarily generalized seizures, age at seizure
      onset, duration of epilepsy, epileptiform discharges in EEG, neuroradiological
      findings and AED schedules with therapeutic response. According to seizure
      frequency, patients were divided into three groups: (1) seizure-free (SF)
      patients at the time of evaluation, (2) patients considered as having infrequent
      seizures (IS) if they presented only auras or up to three dyscognitive (complex
      partial) seizures per year and (3) patients with higher rate were regarded as
      having frequent seizures i.e. being drug-resistant (DR). For each clinical
      parameter, the three groups were compared statistically. In addition, following
      the patterns of evolution over time, patients were categorized into two groups:
      continuous pattern, with no period of remission, and intermittent pattern, in
      which patients had at least one period of remission. RESULTS: Ten patients
      (15.4%) were seizure free, 19 (29.2%) had infrequent seizures, while 36 patients
      (55.4%) had frequent uncontrolled seizures. Ten (52.6%) IS patients and ten
      (27.7%) DR patients had a intermittent i.e. relapse-remitting pattern with at
      least one period of two years without seizures. Female patients dominated SF
      group and the gender difference with other groups reached statistical
      significance (p=0.02). Comparing the groups, DR group had longer seizure duration
      than IS group (12.6+/-10.9years vs. 22.8+/-10.6years, p=0.006). Number of tried
      AEDs (p<0.00006) was significantly lower in the seizure-free patients. Other
      variables are not related to course of the epilepsy. CONCLUSION: MTLE is a
      heterogeneous syndrome, 45% of patients in our series were having either rare
      auras or seizures or were seizure-free. The factors associated with drug
      resistance were longer duration of epilepsy, higher number of previously tried
      AED and male gender.

PMID- 27037864
TI  - Stent-assisted coiling versus coiling alone of ruptured anterior communicating
      artery aneurysms: A single-center experience.
AB  - OBJECTIVE: Endovascular coiling of anterior communicating artery (ACoA) aneurysms
      has evolved; however, stent-assisted coiling of ruptured aneurysms remains
      controversial. We aimed to compare periprocedural complications, angiographic and
      clinical outcomes after stent-assisted coiling with coiling alone of ruptured
      ACoA aneurysms. METHODS: We performed a retrospective review of consecutive 222
      patients with ruptured ACoA aneurysms treated with endovascular coiling within 7
      days after ictus. Patients were grouped into stent-assisted coiling and coiling
      alone groups. Baseline characteristics, periprocedural complications, clinical
      outcomes, and angiographic results were compared between the two groups. RESULTS:
      63 (28.4%) patients underwent stent-assisted coiling and 159 (71.6%) underwent
      coiling alone. There were no statistically significant differences in age, sex,
      clinical grading and Fisher grade. Larger aneurysms (P=0.002) and wider-neck
      aneurysms (P<0.001) were more often treated with stent-assisted coiling within
      72h (P=0.025). Intraprocedural aneurysm rupture occurred in 6 (9.5%) patients
      treated with stent-assisted coiling compared with in 5 (3.1%) treated with
      coiling alone (P<0.048). Thrombus formation occurred in 10 (15.9%) patients after
      stent-assisted coiling compared with 6 (3.8%) after coiling alone (P=0.002).
      Stent-assisted coiling achieved a lower rate of immediate occlusion than coiling
      alone (P=0.045). Postoperative complications, clinical outcomes, and follow-up
      aneurysm occlusion did not significantly differ. CONCLUSIONS: Stent-assisted
      coiling of ruptured ACoA aneurysms was associated with a higher rate of
      intraprocedural complications and associated with a lower immediate occlusion
      rate. However, Postoperative complications and clinical outcomes did not differ.
      Long-term angiographic results require further study.

PMID- 27037865
TI  - Decreased CSF output as a clinical indicator of cerebral vasospasm following
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Vasospasm is a significant cause of morbidity and mortality among
      those with aneurysmal subarachnoid hemorrhage (aSAH). Treating increased
      intracranial pressure by drainage of cerebral spinal fluid through an external
      ventriculostomy is routine practice. The objective of this study is to evaluate
      the trends of CSF output in patients who experience vasospasm. METHODS:
      Electronic medical charts were reviewed to identify two groups of patients with
      aSAH, 75 consecutive patients who developed vasospasm and 75 matched patients who
      did not develop vasospasm. CSF output was recorded within 3 days before and 3
      days after the occurrence of vasospasm. CSF output was recorded for the same days
      after SAH in matched patients with no vasospasm. RESULTS: Total CSF output was
      lower in patients with vasospasm as compared to patients without vasospasm
      matched for the same day (p<0.001). In patients with vasospasm, CSF output
      recordings were significantly higher prior to the occurrence of vasospasm
      (438ml/day) than the period following vasospasm (325.7ml/day), with a consistent
      decrease in CSF drainage from day 3 before vasospasm to day 3 after vasospasm
      (p=0.012). Decreasing CSF output was significantly associated with the occurrence
      of vasospasm (p=0.017). Youden indices demonstrated that daily CSF drainage
      <160ml was significantly associated with the occurrence of vasospasm. The
      sensitivity of this test was 64.79% and the specificity was 55.38%. CONCLUSIONS:
      In addition to clinical exam findings, observation of a CSF output decline to
      less than 160ml/day may be used as additional support for the diagnosis of
      vasospasm.

PMID- 27037866
TI  - Prolonged Ischemic Time, Delayed Graft Function, and Graft and Patient Outcomes
      in Live Donor Kidney Transplant Recipients.
AB  - The association between prolonged cold ischemic time (CIT) and graft and patient
      outcomes in live donor kidney transplant recipients remains unclear. The aims of
      this study were to examine the association of CIT with delayed graft function and
      graft loss in live donor kidney transplant recipients and those who participated
      in the Australian Paired Kidney Exchange program using data from the Australia
      and New Zealand Dialysis and Transplant (ANZDATA) registry. Of 3717 live donor
      transplant recipients between 1997 and 2012 who were followed for a median of 6.6
      years (25 977 person-years), 224 (25%) experienced CIT >4-8 h. Donor age was an
      effect modifier between CIT and graft outcomes. In recipients who received
      kidneys from older donors aged >50 years, every hour of increase in CIT was
      associated with adjusted odds of 1.28 (95% confidence interval [CI] 1.07-1.53, p
      = 0.007) for delayed graft function, whereas CIT >4-8 h was associated with
      adjusted hazards of 1.93 (95% CI 1.21-3.09, p = 0.006) and 1.91 (95% CI 1.05
      3.49, p = 0.035) for overall and death-censored graft loss, respectively,
      compared with CIT of 1-2 h. Attempts to reduce CIT in live donor kidney
      transplants involving older donor kidneys may lead to improvement of graft
      outcomes.

PMID- 27037868
TI  - Reply by Authors.

PMID- 27037867
TI  - Editorial Comment.

PMID- 27037869
TI  - Editorial Comment.

PMID- 27037870
TI  - Reply by Authors.

PMID- 27037871
TI  - Human Fumarate Hydratase Is Dual Localized by an Alternative Transcription
      Initiation Mechanism.
AB  - Fumarate hydratase (FH, fumarase), is a tricarboxylic acid cycle enzyme localized
      in the mitochondrial matrix. However, a common theme, conserved from yeast to
      human, is the existence of a large cytosolic population of FH. FH has been shown
      to function as a tumor suppressor gene and is now implicated in various diseases.
      We have previously indicated that the cytosolic echoform of FH has a role in the
      DNA damage response and specifically in the response to DNA double strand breaks.
      In fact, recently FH has been shown to be involved in histone demethylation.
      Therefore, it has become important to understand the underlying mechanism of FH
      dual subcellular location in human cells. We revealed that in human cells, in
      contrast to yeast, the FH gene encodes two gene products, one containing and one
      lacking the mitochondrial targeting sequence. On the basis of expression of
      endogenous wild-type FH and mutant FH cDNAs from plasmids, RT-PCR, RACE to
      determine the 5' termini of FH mRNAs, and mass spectrometry of FH products, we
      show that the mechanism of FH distribution is alternative transcription
      initiation from a broad promoter. This is contrary to the suggested mechanism for
      rat liver cells which had claimed alternative translation initiation.

PMID- 27037872
TI  - Effects of Exercise on Cognition: The Finnish Alzheimer Disease Exercise Trial: A
      Randomized, Controlled Trial.
AB  - OBJECTIVES: To examine whether a regular, long-term exercise program performed by
      individuals with Alzheimer's disease (AD) at home or as group-based exercise at
      an adult daycare center has beneficial effects on cognition; to examine secondary
      outcomes of a trial that has been published earlier. DESIGN: Randomized,
      controlled trial. SETTING: Community. PARTICIPANTS: Community-dwelling dyads (N =
      210) of individuals with AD and their spousal caregivers randomized into three
      groups. INTERVENTION: Two types of intervention comprising customized home-based
      exercise (HE) and group-based exercise (GE), each twice a week for 1 year, were
      compared with a control group (CG) receiving usual community care. MEASUREMENTS:
      Cognitive function was measured using the Clock Drawing Test (CDT), Verbal
      Fluency (VF), Clinical Dementia Rating (CDR), and Mini-Mental State Examination
      (MMSE) at baseline and 3, 6, and 12 months of follow-up. RESULTS: Executive
      function, measured using CDT, improved in the HE group, and changes in the score
      were significantly better than those of the CG at 12 months (adjusted for age,
      sex, and CDR, P = .03). All groups deteriorated in VF and MMSE score during the
      intervention, and no significant differences between the groups were detected at
      12-month follow-up when analyses were adjusted for age, sex, and CDR. CONCLUSION:
      Regular, long-term, customized HE improved the executive function of community
      dwelling older people with memory disorders, but the effects were mild and were
      not observed in other domains of cognition.

PMID- 27037873
TI  - Psychometric properties of the Drive for Muscularity Scale in Malay men.
AB  - The Drive for Muscularity Scale (DMS) is a widely used measure in studies of
      men's body image, but few studies have examined its psychometric properties
      outside English-speaking samples. Here, we assessed the factor structure of a
      Malay translation of the DMS. A community sample of 159 Malay men from Kuala
      Lumpur, Malaysia, completed the DMS, along with measures of self-esteem, body
      appreciation, and muscle discrepancy. Exploratory factor analysis led to the
      extraction of two factors, differentiating attitudes from behaviours, which
      mirrors the parent scale. Both factors also loaded on to a higher-order drive for
      muscularity factor. The subscales of the Malay DMS had adequate internal
      consistencies and good convergent validity, insofar as significant relationships
      were reported with self-esteem, body appreciation, muscle discrepancy, and body
      mass index. These results indicate that the Malay DMS has acceptable psychometric
      properties and can be used to assess body image concerns in Malay men. 

PMID- 27037874
TI  - Glutathione analogues as substrates or inhibitors that discriminate between
      allozymes of the MDR-involved human glutathione transferase P1-1.
AB  - Glutathione (GSH) structure-guided tripeptide analogues were designed and
      synthesized by solid phase technology, purified (>=95%) by RP and/or GF column
      chromatography, to identify those that, compared with GSH, exhibited similar or
      higher binding and catalytic efficiency toward the MDR-involved human GSTP1-1
      isoenzyme, and could discriminate between the allozymic expression products of
      the polymorphic human GSTP1 gene locus, designated as hGSTP1*A (Ile(104)
      /Ala(113) ), hGSTP1*B (Val(104) /Ala(113) ), and hGSTP1*C (Val(104) /Val(113) ).
      The analogues bear single amino acid alterations as well as alterations in more
      than one position. Some analogues showed remarkable allozyme selectivity, binding
      catalytically to A (I, II, IV, XII), to C (V and XVI), to A and C (III, VII, XIV)
      or to all three allozymes (XV). A heterocyclic substituent at positions 1 or 2 of
      GSH favors inhibition of A, whereas a small hydrophobic/hydrophilic amide
      substituent at position 2 (Cys) favors inhibition of B and C. Heterocyclic
      substituents at position 1, only, produce catalytic analogues for A, whereas less
      bulky and more flexible hydrophobic/hydrophilic substituents, at positions 1 or
      3, lead to effective substrates with C. When such substituents were introduced
      simultaneously at positions 1 and 3, the analogues produced have no catalytic
      potential but showed appreciable inhibitory effects, instead, with all allozymes.
      It is anticipated that when GSH analogues with selective inhibitory or catalytic
      binding, were conjugated to allozyme-selective inhibitors of hGSTP1-1, the
      derived leads would be useful for the designing of novel chimeric inhibitors
      against the MDR-involved hGSTP1-1 allozymes. (c) 2016 Wiley Periodicals, Inc.
      Biopolymers (Pept Sci) 106: 330-344, 2016. 

PMID- 27037875
TI  - Electrocoagulation mechanism of perfluorooctanoate (PFOA) on a zinc anode:
      Influence of cathodes and anions.
AB  - Batch experiments were conducted to investigate the effects of cathode materials
      and anions (Cl(-), SO4(2-), NO3(-), and CO3(2-)/HCO3(-)) on perfluorooctanoate
      (PFOA) removal in electrocoagulation process using zinc anode. The results
      indicated that the hydroxide flocs generated in-situ in the electrocoagulation
      process using the stainless steel rod as cathode were more effective than those
      using aluminum rod as cathode for the removal of PFOA after 20min of
      electrocoagulation at a current density of 0.5mAcm(-2). Hydroxide flocs generated
      in-situ in the electrocoagulation in the presence of Cl(-)/NO3(-) could
      effectively remove PFOA from aqueous solution with the removal ratios of
      99.7%/98.1% and 98.9%/97.3% using stainless steel rod and aluminum rod as
      cathode, respectively. However, the PFOA removal ratios were 96.2%/4.1% and
      7.4%/4.6% using stainless steel rod and aluminum rod as cathode, respectively, in
      the presence of SO4(2-) and CO3(2-)/HCO3(-). The different removal ratios of PFOA
      during the electrocoagulation process were primarily due to the fact that the
      hydroxide flocs generated in-situ were different in the presence of diverse
      cathodes and anions. We firstly demonstrated that Zn0.70Al0.30(OH)2(CO3)0.15.xH2O
      and ZnO generated in-situ in the electrocoagulation process (except for CO3(2
      )/HCO3(-)) using zinc anode and aluminum/stainless steel rod cathode governed the
      sorption of PFOA. The adsorbent hydroxide flocs in-situ generated in the presence
      of Cl(-) could effectively remove PFOA from aqueous solution containing CO3(2
      )/HCO3(-) anion at the initial hydroxide flocs concentration of 2000mgL(-1).
      These results provided an effective and alternative method to remove PFOA from
      aqueous solution containing CO3(2-)/HCO3(-) anion.

PMID- 27037876
TI  - Assessing the relation between anthropogenic pressure and PAH concentrations in
      surface water in the Seine River basin using multivariate analysis.
AB  - Understanding the relation between polycyclic aromatic hydrocarbons (PAHs) in
      freshwater and anthropogenic pressure is fundamental to finding a solution to
      reduce the presence of PAHs in water, and thus their potential impact on aquatic
      life. In this paper we propose to gain greater insight into the variability,
      sources and partitioning of PAHs in labile (or freely dissolved=not associated to
      the organic matter), dissolved and particulate phases in freshwater. This study
      was conducted using land use data as a marker of anthropogenic pressure and
      coupling it with chemical measurements. This study was conducted on 30 sites in
      the Seine River basin, which is subjected to a strong human impact and exhibits a
      wide range of land uses. Half of the sites were studied twice. Labile PAHs were
      measured by semi-permeable membrane devices (SPMDs), and dissolved and
      particulate phases by grab samples. Partial least squares regressions were
      performed between chemical measurements and data of anthropogenic pressure. The
      results indicate different sources for the dissolved phase and particles.
      Dissolved and labile phases were more related to the population density of the
      watershed, while particles were more related to a local pressure. Season and land
      use data are necessary information to correctly interpret and compare PAH
      concentrations from different sites. Furthermore, the whole data set of the 45
      field deployments comprising labile, dissolved, total and particulate PAH
      concentrations as well as the physico-chemical parameters is available in the
      supplementary information.

PMID- 27037877
TI  - Indonesia palm oil production without deforestation and peat conversion by 2050.
AB  - Palm oil is a promising source of cooking oil and biodiesel. The demand for palm
      oil has been increasing worldwide. However, concerns exist surrounding the
      environmental and socio-economic sustainability of palm oil production. Indonesia
      is a major palm oil producing country. We explored scenarios for palm oil
      production in Indonesia until 2050, focusing on Sumatra, Kalimantan and Papua.
      Our scenarios describe possible trends in crude palm oil production in Indonesia,
      while considering the demand for cooking oil and biodiesel, the available land
      for plantations, production capacity (for crude palm oil and fresh fruit bunches)
      and environmentally restricting conditions. We first assessed past developments
      in palm oil production. Next, we analysed scenarios for the future. In the past
      20years, 95% of the Indonesian oil palm production area was in Sumatra and
      Kalimantan and was increasingly cultivated in peatlands. Our scenarios for the
      future indicate that Indonesia can meet a considerable part of the global and
      Asian demand for palm oil, while avoiding further cultivation of peatlands and
      forest. By 2050, 264-447Mt crude palm oil may be needed for cooking oil and
      biodiesel worldwide. In Indonesia, the area that is potentially suitable for oil
      palm is 17 to 26Mha with a potential production rate of 27-38t fresh fruit
      bunches/ha, yielding 130-176Mt crude palm oil. Thus Indonesia can meet 39-60% of
      the international demand. In our scenarios this would be produced in Sumatra (21
      26%), Kalimantan (12-16%), and Papua (2%). The potential areas include the
      current oil palm plantation in mineral lands, but exclude the current oil palm
      plantations in peatlands.

PMID- 27037878
TI  - Polybrominated diphenyl ethers in dissolved and suspended phases of seawater and
      in surface sediment from Jiaozhou Bay, North China.
AB  - The concentration and distribution of polybrominated diphenyl ethers (PBDEs) in
      the dissolved phase (DP) and suspended particulate matter (SPM) of seawater and
      in surface sediment obtained from Jiaozhou Bay (JZB) were determined. The
      potential sources of these compounds were evaluated. The total concentrations of
      14 PBDEs (?14PBDE) in DP and SPM were 0.09-1.35 and 1.17-5.45ng/L, respectively,
      indicating that the PBDE congeners are predominantly partitioned into the SPM
      fraction. The ?14PBDE concentrations in sediment ranged from 2.18ng/g to
      10.59ng/g with a mean value of 6.59ng/g. BDE-209 was dominant among 14 PBDE
      congeners, and BDE-47 was another abundant congener in the SPM and sediment
      samples. The PBDE concentration in SPM showed a significantly positive
      correlation with chlorophyll a level (r(2)=0.496, p<0.05), and that in the
      sediment exhibited a significantly positive correlation with clay proportion
      (r(2)=0.846, p<0.01). This result suggests that the phytoplankton or debris in
      the suspended particulates play an important role in PBDE accumulation and
      transportation and that PBDEs are preferentially enriched in clays in the
      sediment. PBDE concentrations were higher in the inner and mouth regions than in
      the outer and middle regions, and decreased with water depth in the water column.
      Non-parametric multidimensional scaling ordination showed that BDE-209 and BDE-47
      are the important products discriminating PBDE contamination. This result is
      associated with industrial waste discharge from urban areas and with heavy ship
      traffic, indicating that DecaBDE and PentaBDE products are the potential sources
      of PBDEs. PBDE concentrations were lower in the sediment in JZB than in other
      coastal areas in South China, although the PBDE concentrations in DP were higher
      than those in some coastal areas worldwide. Moreover, the PBDE concentrations in
      DP and sediment increased in the last decade.

PMID- 27037879
TI  - Dissolved organic carbon in a constructed and natural fens in the Athabasca oil
      sands region, Alberta, Canada.
AB  - In the Athabasca oil sands region near Fort McMurray, Alberta, Canada, peatlands
      are disturbed extensively in order to recover bitumen below the surface. Hence,
      following oil sands mining, landscape reclamation is a part of the mine closure
      process in order to return functioning ecosystems, including peatlands, to the
      region. This study was conducted at a pilot fen reclamation project and three
      other diverse natural (poor, rich and saline) fens in the oil sands region during
      the growing seasons of 2013 and 2014, the first and second year post
      construction. Ecosystem functioning of the constructed fen (CF) was evaluated
      with reference to natural fens based on pore water dissolved organic carbon (DOC)
      concentration and chemistry. Significant variation of DOC concentration among the
      reference fens was observed, varying from an average of 42.0mg/L at the rich fen
      (RF) to 70.8mg/L at the saline fen (SF). Dissolved organic carbon concentration
      at CF was significantly lower than at all reference fens, but increased
      significantly over the first two years. Seasonal variation of DOC concentration
      was also observed in each site with concentration increasing over the growing
      season. At CF, DOC was comprised of larger, more humic and complex aromatic
      compounds than reference fens in the first year post-construction based on its
      spectrophotometric properties; however, these differences were reduced in the
      second year. Initial DOC concentration and chemistry at CF was indicative of the
      source being largely the peat placed during fen construction. Changes in
      chemistry and increasing concentration of DOC in the second growing season likely
      resulted from increasing inputs from plants established on site. These results
      suggest that DOC concentration is likely to increase in future at CF as vascular
      plant productivity increases and in response to salinity sourced from tailing
      sand used to construct the catchment.

PMID- 27037880
TI  - A mathematical model for soil solute transfer into surface runoff as influenced
      by rainfall detachment.
AB  - Nutrients transport is a main source of water pollution. Several models
      describing transport of soil nutrients such as potassium, phosphate and nitrate
      in runoff water have been developed. The objectives of this research were to
      describe the nutrients transport processes by considering the effect of rainfall
      detachment, and to evaluate the factors that have greatest influence on nutrients
      transport into runoff. In this study, an existing mass-conservation equation and
      rainfall detachment process were combined and augmented to predict runoff of
      nutrients in surface water in a Loess Plateau soil in Northwestern Yangling,
      China. The mixing depth is a function of time as a result of rainfall impact, not
      a constant as described in previous models. The new model was tested using two
      different sub-models of complete-mixing and incomplete-mixing. The complete
      mixing model is more popular to use for its simplicity. It captured the runoff
      trends of those high adsorption nutrients, and of nutrients transport along steep
      slopes. While the incomplete-mixing model predicted well for the highest observed
      concentrations of the test nutrients. Parameters inversely estimated by the
      models were applied to simulate nutrients transport, results suggested that both
      models can be adopted to describe nutrients transport in runoff under the impact
      of rainfall.

PMID- 27037881
TI  - Examining the relationship between environmental factors and conflict in
      pastoralist areas of East Africa.
AB  - The eastern Africa region has long been known for recurring drought, prolonged
      civil war and frequent pastoral conflicts. Several researchers have suggested
      that environmental factors can trigger conflicts among pastoralist communities,
      but quantitative support for this hypothesis is lacking. Here we use 29years of
      georeferenced precipitation and Normalized Difference Vegetation Index (NDVI)
      data to evaluate long term trends in scarcity of water and forage for livestock,
      and then ask whether these environmental stressors have any predictive power with
      respect to the location and timing of 11years of conflict data based on Armed
      Conflict Location and Event Data Project (ACLED) and Uppsala Conflict Data
      Program (UCDP). Results indicate that environmental stressors were only partly
      predictive of conflict events. To better understand the drivers behind conflict,
      the contribution of other potential stressors to conflict need to be
      systematically quantified and be taken into consideration.

PMID- 27037882
TI  - Parallel pathways of ethoxylated alcohol biodegradation under aerobic conditions.
AB  - Non-ionic surfactants (NS) are a major component of the surfactant flux
      discharged into surface water, and alcohol ethoxylates (AE) are the major
      component of this flux. Therefore, biodegradation pathways of AE deserve more
      thorough investigation. The aim of this work was to investigate the stages of
      biodegradation of homogeneous oxyethylated dodecanol C12E9 having 9 oxyethylene
      subunits, under aerobic conditions. Enterobacter strain Z3 bacteria were chosen
      as biodegrading organisms under conditions with C12E9 as the sole source of
      organic carbon. Bacterial consortia of river water were used in a parallel test
      as an inoculum for comparison. The LC-MS technique was used to identify the
      products of biodegradation. Liquid-liquid extraction with ethyl acetate was
      selected for the isolation of C12E9 and metabolites from the biodegradation
      broth. The LC-MS/MS technique operating in the multiple reaction monitoring (MRM)
      mode was used for quantitative determination of C12E9, C12E8, C12E7 and C12E6.
      Apart from the substrate, the homologues C12E8, C12E7 and C12E6, being
      metabolites of C12E9 biodegradation by shortening of the oxyethylene chain, as
      well as intermediate metabolites having a carboxyl end group in the oxyethylene
      chain (C12E8COOH, C12E7COOH, C12E6COOH and C12E5COOH), were identified.
      Poly(ethylene glycols) (E) having 9, 8 and 7 oxyethylene subunits were also
      identified, indicating parallel central fission of C12E9 and its metabolites.
      Similar results were obtained with river water as inoculum. It is concluded that
      AE, under aerobic conditions, are biodegraded via two parallel pathways: by
      central fission with the formation of PEG, and by Omega-oxidation of the
      oxyethylene chain with the formation of carboxylated AE and subsequent shortening
      of the oxyethylene chain by a single unit.

PMID- 27037883
TI  - Determination of fluoroquinolone antibiotic residues in the plasma of Eurasian
      griffon vultures (Gyps fulvus) in Spain.
AB  - Due to the possible toxicological impact, the accumulation of pharmaceuticals in
      wildlife as a consequence of human practices is of growing concern. The
      consumption of carrion at feeding stations - the so-called 'vulture restaurants' 
      with no management of the veterinary drugs it contains may expose scavengers to
      pharmaceuticals. To demonstrate this, we analyzed plasma from Eurasian griffon
      vultures (Gyps fulvus) originating from two different areas of Spain for
      antibiotics such as enrofloxacin and ciprofloxacin, its primary metabolite.
      Quinolone residues were detected in about 65% (n=106) of birds, of which 15.1%
      (16/106) had quantifiable amounts of enrofloxacin (0.049+/-0.102MUg/mL) and 5.7%
      (6/106) of ciprofloxacin (0.009+/-0.007MUg/mL). The differences in exposure
      between the two sampled areas are attributable to different types of carrion
      management: the vultures that fed in areas with a high density of dead livestock
      (supplied directly to feeding stations) were more prone to exposure than those
      that sought food in areas where carcass availability is more unpredictable. Our
      findings are evidence that vultures have access to medicated livestock and that
      there are quantifiable levels of livestock antibiotics in vulture plasma.
      However, the vultures analyzed in this study had maximum antibiotic
      concentrations of only 0.4MUg/mL, much less than the concentrations used in the
      clinical treatment of scavengers and a level that is probably too small to cause
      intoxication.

PMID- 27037884
TI  - Effects of long-term greywater disposal on soil: A case study.
AB  - This study investigated the environmental health risks to soil and potential
      risks to groundwater associated with long term (8-18years) greywater disposal
      practices. Land application of greywater is likely to have environmental impacts,
      which may be positive or negative. Greywater can contain plant macronutrients
      that may benefit plant growth. Conversely, high levels of surfactants, oils,
      grease, sodium and potentially pathogenic organisms may negatively impact
      environmental and human health. In this study, land disposal of untreated
      greywater was practiced at five coastal domestic properties. At each property,
      soil samples were collected at two depths from areas used for greywater disposal
      and from control areas that were not exposed to greywater. Soils were analysed
      for chemical and biological responses to greywater exposure. Generally, greywater
      irrigated soils had higher pH, Olsen P, base saturation, and increased soil
      microbial activity (as measured by biomass carbon, basal respiration and
      dehydrogenase activity). A pH of >9 was recorded for some greywater treated soil
      samples. Escherichia coli (E. coli) were detected at up to 10(3)MPN/g in the
      greywater exposed surface soils at some sites. Terminal Restriction Fragment
      Length Polymorphism (TRFLP) analysis revealed that greywater affected the soil
      microbial community structure, which may have implications for soil health and
      fertility. Overall, this study shows that the long-term application of greywater
      at the investigated sites had a moderate impact on the soil environment. This may
      have been due to the sandy soils and high rainfall that would flush the soil.
      Increases in microbial biomass and dehydrogenase indicate that greywater
      application may be beneficial for plant growth. However, high levels of E. coli
      in some soils may be a risk to human health and sub-surface irrigation should be
      the recommended application method.

PMID- 27037885
TI  - How benthic diatoms within natural communities respond to eight common herbicides
      with different modes of action.
AB  - Herbicides are common pollutants of rivers in agricultural regions. These
      contaminants include various types of chemicals with different modes of toxic
      action. Herbicides can have toxic effects on freshwater benthic diatoms, the base
      of the aquatic food web. We examined the effects of (non-mixture) herbicide
      exposure to the health of diatoms for eight common herbicides with three
      different modes of action; the photosystem II (PSII) inhibitors: atrazine,
      simazine, hexazinone, tebuthiuron and diuron; two auxinic herbicides: MCPA and
      2,4-D; and the EPSP synthase inhibitor: glyphosate. Benthic diatoms within
      riverine communities were exposed to each herbicide in rapid toxicity tests at
      concentrations of 50, 200 and 500MUgL(-1). The most sensitive taxa were
      Gomphonema spp. and Encyonema gracilis. Navicula cryptotenella was the most
      tolerant to herbicide exposure. There was no significant effect of the different
      herbicide modes of action at the community level. Herbicide mode of action did
      not alter which taxa were most sensitive within the community and sensitivity
      rankings of the dominant diatom taxa were similar for each of the eight
      herbicides. The consistency of the results between herbicides suggests that
      freshwater benthic diatoms may be suitable in situ indicators for detecting the
      toxicity of herbicides with differing modes of action.

PMID- 27037886
TI  - Short-chain chlorinated paraffins in the soils of two different Chinese cities:
      Occurrence, homologue patterns and vertical migration.
AB  - Short-chain chlorinated paraffins (SCCPs) are candidate persistent organic
      pollutants (POPs) that are under review by the Stockholm Convention. China is
      currently the largest producer and consumer of chlorinated paraffins (CPs). To
      study the environmental behavior and fate of SCCPs in the soils of urban and
      suburban regions, the SCCP concentrations in 88 topsoils and 15 soil columns from
      land of different use types (e.g., woodland, vegetable field, paddy field and
      greenbelt) from Guangzhou and Chengdu have been determined. The SCCP
      concentrations in topsoils from Guangzhou (range: 1.45-25.5ngg(-1) dry weight
      (dw), average: 10.3ngg(-1) dw) were much higher than those from Chengdu (range:
      0.218-3.26ngg(-1) dw, average: 1.43ngg(-1) dw). When compared to previously
      reported SCCP levels for topsoils from other areas, the SCCP concentrations
      measured in the present work were quite low. Much higher SCCP concentrations were
      observed in the greenbelt topsoils from Chengdu relative to the values measured
      from woodlands and vegetable and paddy fields. The composition profiles suggest
      that C10Cl6-10 and C11-13Cl6-8 were the major groups of SCCPs in topsoils from
      the woodlands and vegetable and paddy fields in Guangzhou and Chengdu. Vertical
      variations of the SCCP concentrations in the soil columns suggest that less
      chlorinated SCCPs (Cl5-6-SCCPs) are more capable of migrating to the deeper-layer
      soils than more chlorinated ones (Cl9-10-SCCPs). The SCCP concentrations
      displayed little dependence on organic matter (OM) for most topsoils (p>0.05),
      indicating that OM is not the controlling factor in the distribution of SCCPs in
      the soils. CAPSULE: This study analyzed the occurrence, homologue patterns and
      vertical migration of SCCPs in the topsoils of two Chinese cities with different
      industrial structures and climate conditions.

PMID- 27037887
TI  - Stress-related phenomena and detoxification mechanisms induced by common
      pharmaceuticals in alfalfa (Medicago sativa L.) plants.
AB  - Pharmaceutically active compounds (PhACs) have been recently shown to exert
      phytotoxic effects. The present study explores the uptake, systemic
      translocation, and abiotic stress responses and detoxification mechanisms induced
      by the exposure of alfalfa plants grown in sand under greenhouse conditions to
      four common, individually applied PhACs (10MUgL(-1)) (diclofenac,
      sulfamethoxazole, trimethoprim, 17a-ethinylestradiol) and their mixture. Stress
      physiology markers (lipid peroxidation, proline, H2O2 and NO content, antioxidant
      activity assays) and gene expression levels of key plant detoxification
      components (including glutathione S-transferases, GST7, GST17; superoxide
      dismutases, CuZnSOD, FeSOD; proton pump, H(+)-ATP, and cytochrome c oxidase,
      CytcOx), were evaluated. PhACs were detected in significantly higher
      concentrations in roots compared with leaves. Stress related effects, manifested
      via membrane lipid peroxidation and oxidative burst, were local (roots) rather
      than systemic (leaves), and exacerbated when the tested PhACs were applied in
      mixture. Systemic accumulation of H2O2 in leaves suggests its involvement in
      signal transduction and detoxification responses. Increased antioxidant enzymatic
      activities, as well as upregulated transcript levels of GST7, GST17, H(+)-ATPase
      and CytcOx, propose their role in the detoxification of the selected PhACs in
      plants. The current findings provide novel biochemical and molecular evidence
      highlighting the studied PhACs as an emerging abiotic stress factor, and point
      the need for further research on wastewater flows under natural agricultural
      environments.

PMID- 27037888
TI  - Optical properties of PM2.5 and the impacts of chemical compositions in the
      coastal city Xiamen in China.
AB  - Continuous in situ measurements of optical properties of fine aerosols (PM2.5)
      were conducted in the urbanized coastal city Xiamen in Southeast China from
      November 2013 to January 2014. PM2.5 samples were also collected and chemical
      compositions including organic carbon (OC), elemental carbon (EC) and water
      soluble inorganic ions were determined to investigate the impacts of chemical
      compositions on aerosol optical properties. Average values of scattering
      coefficient (bscat), absorption coefficient (babs), extinction coefficient (bext)
      and single scattering albedo (SSA) were 164.0Mm(-1), 22.4Mm(-1), 187.0Mm(-1) and
      0.88, respectively. bscat, babs and bext showed obvious bi-modal diurnal
      variations with high values in the morning and at night while low value in the
      early afternoon, whereas SSA exhibited an opposite diurnal variation. Average
      bscat and babs were largest in the wind direction of southwest and were larger
      with slower wind. babs was mainly affected by EC, while bscat was affected by
      ammonium, sulfate, nitrate and OC. The IMPROVE formula was applied to estimate
      bext based on the chemical species. Results shows that ammonium sulfate was the
      largest contributor, accounting for 36.4% of bext, followed by organic matter
      (30.6%), ammonium nitrate (20.1%), EC (9.0%) and sea salt (3.9%). The
      deterioration in visibility was mainly led by increases in secondary aerosols
      including sulfate and nitrate. Backward trajectories analysis showed that during
      the sampling period Xiamen was significantly affected by the air masses
      originating from the Northern and Northeastern areas. Air masses from the
      Northern associated with relative higher bext and less relative contribution from
      ammonium sulfate and more relative contribution from ammonium nitrate, organic
      matter and sea salt.

PMID- 27037889
TI  - The impact of a smoke-free policy on environmental tobacco smoke exposure in
      public housing developments.
AB  - BACKGROUND: Smoke-free housing policies have the potential to reduce secondhand
      smoke (SHS) exposures for residents of multi-unit housing. Since common areas
      represent a pathway of SHS movement between units, smoke-free policies would be
      expected to reduce SHS in these microenvironments. METHODS: Week-long air
      nicotine and PM2.5 (particulate matter below 2.5MUm in aerodynamic diameter)
      samples were collected in the common areas of 10 Boston Housing Authority (BHA)
      and 6 Cambridge Housing Authority (CHA) buildings from January 2012 to October
      2013. We also measured one outdoor PM level at each study building. Samples from
      BHA included pre and post- smoke-free policy measurements. Each development was
      visited three times over the course of the study period. The effect of the
      smoking ban on indoor PM2.5 was examined using generalized mixed effect models to
      accommodate repeated measurement at each site. Changes in nicotine concentrations
      were modeled using quantile mixed regression to reduce the impact of outliers.
      RESULTS: After controlling for season, site, and background PM2.5 concentrations,
      PM2.5 levels were 4.05MUg/m(3) (p-value=0.09) lower in BHA after the smoke-free
      policy was implemented in the summer of 2012, compared with CHA developments,
      which had no smoking policy in place. Similarly, nicotine levels decreased by 57%
      (p-value=0.08) in Boston relative to Cambridge after the ban. CONCLUSIONS: Our
      findings support the use of smoke-free policies as an effective tool to reduce
      SHS exposure and protect non-smokers, especially residents of multi-unit housing.

PMID- 27037890
TI  - PAH determination based on a rapid and novel gas purge-microsyringe extraction
      (GP-MSE) technique in road dust of Shanghai, China: Characterization, source
      apportionment, and health risk assessment.
AB  - A novel cleanup technique termed as gas purge-microsyringe extraction (GP-MSE)
      was evaluated and applied for polycyclic aromatic hydrocarbon (PAH) determination
      in road dust samples. A total of 68 road dust samples covering almost the entire
      Shanghai area were analyzed for 16 priority PAHs using gas chromatography-mass
      spectrometry. The results indicate that the total PAH concentrations over the
      investigated sites ranged from 1.04MUg/g to 134.02MUg/g dw with an average of
      13.84MUg/g. High-molecular-weight compounds (4-6 rings PAHs) were significantly
      dominant in the total mass of PAHs, and accounted for 77.85% to 93.62%.
      Diagnostic ratio analysis showed that the road dust PAHs were mainly from the
      mixture of petroleum and biomass/coal combustions. Principal component analysis
      in conjunction with multiple linear regression indicated that the two major
      origins of road dust PAHs were vehicular emissions and biomass/fossil fuel
      combustions, which contributed 66.7% and 18.8% to the total road dust PAH burden,
      respectively. The concentration of benzo[a]pyrene equivalent (BaPeq) varied from
      0.16MUg/g to 24.47MUg/g. The six highly carcinogenic PAH species
      (benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene,
      dibenz(a,h)anthracene, and indeno(1,2,3-cd)pyrene) accounted for 98.57% of the
      total BaPeq concentration. Thus, the toxicity of PAHs in road dust was highly
      associated with high-molecular-weight compounds.

PMID- 27037891
TI  - Seasonal and regional variations of source contributions for PM10 and PM2.5 in
      urban environment.
AB  - To characterize the sources of to PM10 and PM2.5, a long-term, speciate and
      simultaneous dataset was sampled in a megacity in China during the period of 2006
      2014. The PM concentrations and PM2.5/PM10 were higher in the winter. Higher
      percentages of Al, Si, Ca and Fe were observed in the summer, and higher
      concentrations of OC, NO3(-) and SO4(2-) occurred in the winter. Then, the
      sources were quantified by an advanced three-way model (defined as an ABB three
      way model), which estimates different profiles for different sizes. A higher
      percentage of cement and crustal dust was present in the summer; higher fractions
      of coal combustion and nitrate+SOC were observed in the winter. Crustal and
      cement contributed larger portion to coarse part of PM10, whereas vehicular and
      secondary source categories were enriched in PM2.5. Finally, potential source
      contribution function (PSCF) and source regional apportionment (SRA) methods were
      combined with the three-way model to estimate geographical origins. During the
      sampling period, the southeast region (R4) was an important region for most
      source categories (0.6%-11.5%); the R1 (centre region) also played a vital role
      (0.3-6.9%).

PMID- 27037892
TI  - Edible plants for oral delivery of biopharmaceuticals.
AB  - Molecular farming is the use of plants for the production of high value
      recombinant proteins. Over the last 25 years, molecular farming has achieved the
      inexpensive, scalable and safe production of pharmaceutical proteins using a
      range of strategies. One of the most promising approaches is the use of edible
      plant organs expressing biopharmaceuticals for direct oral delivery. This
      approach has proven to be efficacious in several clinical vaccination and
      tolerance induction trials as well as multiple preclinical studies for disease
      prevention. The production of oral biopharmaceuticals in edible plant tissues
      could revolutionize the pharmaceutical industry by reducing the cost of
      production systems based on fermentation, and also eliminating expensive
      downstream purification, cold storage and transportation costs. This review
      considers the unique features that make plants ideal as platforms for the oral
      delivery of protein-based therapeutics and describes recent developments in the
      production of plant derived biopharmaceuticals for oral administration.

PMID- 27037893
TI  - Identification and functional characterization of a glucose regulated protein 94
      gene in Litopenaeus vannamei and its responsiveness in WSSV infection.
AB  - In the current study, a cDNA of glucose regulated protein 94 (LvGRP94) was cloned
      from Litopenaeus vannamei. Subcellular localization assay revealed that LvGRP94
      expressed in endoplasmic reticulum (ER). And results of reported gene assays
      demonstrated that the promoter of LvGRP94 was activated by L. vannamei leucine
      zipper domain transcription factor X-box binding protein 1 (LvXBP1) or heat shock
      treatment. Furthermore, LvGRP94 was found to highly express in hemocytes as well
      as in epidermis by real-time RT-PCR. In addition, it was shown that LvGRP94
      inhibited by LvXBP1 knocked-down in the hemocytes, was induced by white spot
      syndrome virus (WSSV) infection, or unfolded protein response (UPR) pathway
      activation. Importantly, decreasing LvGRP94 reduced the cumulative mortality of
      WSSV-infected shrimps and WSSV copies in shrimp muscle. These results suggested
      that LvGRP94 might involve in shrimp UPR pathway as well as WSSV infection.

PMID- 27037894
TI  - Tfh cell-mediated humoral immune response and HBsAg level can predict HBeAg
      seroconversion in chronic hepatitis B patients receiving peginterferon-alpha
      therapy.
AB  - Hepatitis B e antigen (HBeAg) seroconversion constitutes a significant milestone
      in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB), but
      studies have yet to identify the specific humoral immune mechanisms behind the
      process or any accurate markers that can determine the virus-host immune status
      and, thereby, predict the degree of HBeAg seroconversion achievable. In the
      present longitudinal study, higher frequencies of circulating CXCR5(+)CD4(+) T
      cells and CD19(+)CD38(+) B cells were found in peginterferon-alpha treated HBeAg
      positive CHB patients in whom HBeAg seroconversion had been achieved. What's
      more, both cell types peaked at 24 weeks for the HBeAg seroconversion group,
      while showing only a slight variation in the HBeAg non-seroconversion group. In
      addition, circulating CXCR5(+)CD4(+) T cells and hepatitis B surface antigens
      (HBsAg) were assessed at 24 weeks and 12 weeks, respectively, and the use of
      their ratio was explored in terms of its ability to predict HBeAg seroconversion.
      CONCLUSION: Dysfunction of the humoral immune response mediated by CXCR5(+)CD4(+)
      T cells is associated with the failure of HBeAg seroconversion. The
      CXCR5(+)CD4(+) T cells/HBsAg ratio is an ideal marker for predicting HBeAg
      seroconversion in CHB patients.

PMID- 27037895
TI  - Modulation of Mammary Stromal Cell Lactate Dynamics by Ambient Glucose and
      Epithelial Factors.
AB  - Hyperglycemia is a risk factor for a variety of human cancers. Increased access
      to glucose and that tumor metabolize glucose by a glycolytic process even in the
      presence of oxygen (Warburg effect), provide a framework to analyze a particular
      set of metabolic adaptation mechanisms that may explain this phenomenon. In the
      present work, using a mammary stromal cell line derived from healthy tissue that
      was subjected to a long-term culture in low (5 mM) or high (25 mM) glucose, we
      analyzed kinetic parameters of lactate transport using a FRET biosensor. Our
      results indicate that the glucose pre-culture and soluble epithelial factors
      constitute a stimulus for lactate stromal production, factors that also modify
      the kinetic parameters and the monocarboxylate transporters expression in stromal
      cells. We also observed a vectorial flux of lactate from stroma to epithelial
      cells in a co-culture setting and found that the uptake of lactate by epithelial
      cells correlates with the degree of malignancy. Glucose preconditioning of the
      stromal cell stimulated epithelial motility. Our findings suggest that lactate
      generated by stromal cells in the high glucose condition stimulate epithelial
      migration. Overall, our results support the notion that glucose not only provides
      a substrate for tumor nutrition but also behaves as a signal promoting
      malignancy. J. Cell. Physiol. 232: 136-144, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27037896
TI  - Clinical and immunological features and outcome of anti-p200 pemphigoid.
AB  - BACKGROUND: Anti-p200 pemphigoid is a rare autoimmune blistering disease (AIBD)
      of the dermoepidermal junction, characterized by autoantibodies to laminin
      gamma1. The clinical course of anti-p200 pemphigoid in patients remains poorly
      investigated. OBJECTIVES: We aimed to describe the clinical and immunological
      features and the course of a series of patients with anti-p200 pemphigoid.
      METHODS: We conducted a retrospective study by immunoblotting detection of sera
      on 200-kDa dermal protein extracts from the register of the French reference
      centre for AIBD. We recorded the clinical and immunological features and the
      course of patients. RESULTS: A total of 14 patients with a mean age 81.6 +/- 6.5
      years were included. Only one patient had an associated neurological condition
      and one had psoriasis. Twelve patients had atypical clinical presentation,
      including eczematous, urticarial, prurigo-like, dyshydrosis-like and rosette-like
      skin lesions. Eight patients (57%) had mucosal involvement. Immunoblot analysis
      of sera on dermal and epidermal extracts showed a 200-kDa band in 14 and 10
      cases, respectively. All eight of the sera tested by enzyme-linked immunosorbent
      assay detected recombinant human laminin gamma1. Disease control was obtained in
      six of nine patients treated with topical corticosteroids, and four of five
      patients who received systemic treatment. Seven patients relapsed (50%) and five
      patients (36%) died during the median follow-up time of 12.6 months. At the end
      of the study, only one of the nine living patients was in complete remission off
      therapy. CONCLUSIONS: Many patients with anti-p200 pemphigoid had heterogeneous
      clinical presentation and a more severe prognosis than previously suspected.

PMID- 27037897
TI  - Mandate-based health reform and the labor market: Evidence from the Massachusetts
      reform.
AB  - We model the labor market impact of the key provisions of the national and
      Massachusetts "mandate-based" health reforms: individual mandates, employer
      mandates, and subsidies. We characterize the compensating differential for
      employer-sponsored health insurance (ESHI) and the welfare impact of reform in
      terms of "sufficient statistics." We compare welfare under mandate-based reform
      to welfare in a counterfactual world where individuals do not value ESHI. Relying
      on the Massachusetts reform, we find that jobs with ESHI pay $2812 less annually,
      somewhat less than the cost of ESHI to employers. Accordingly, the deadweight
      loss of mandate-based health reform was approximately 8 percent of its potential
      size. 

PMID- 27037898
TI  - Neuroscience of aesthetics.
AB  - Aesthetic evaluations are appraisals that influence choices in important domains
      of human activity, including mate selection, consumer behavior, art appreciation,
      and possibly even moral judgment. The nascent field of neuroaesthetics is
      advancing our understanding of the role of aesthetic evaluations by examining
      their biological bases. Here, we conduct a selective review of the literature on
      neuroaesthetics to demonstrate that aesthetic experiences likely emerge from the
      interaction between emotion-valuation, sensory-motor, and meaning-knowledge
      neural systems. This tripartite model can in turn be evoked to explain phenomena
      central to aesthetics, such as context effects on preferences. Indeed, context
      dependent appraisals that focus on objects rather than on outcomes could be an
      important factor distinguishing aesthetic experiences from other kinds of
      evaluations.

PMID- 27037899
TI  - Maternal glucose intolerance reduces offspring nephron endowment and increases
      glomerular volume in adult offspring.
AB  - BACKGROUND: Animal studies report a nephron deficit in offspring exposed to
      maternal diabetes, yet are limited to models of severe hyperglycaemia which do
      not reflect the typical clinical condition and which are associated with foetal
      growth restriction that may confound nephron endowment. We aimed to assess renal
      morphology and function in offspring of leptin receptor deficient mice (Leprdb
      /+) and hypothesized that exposure to impaired maternal glucose tolerance (IGT)
      would be detrimental to the developing kidney. METHODS: Nephron endowment was
      assessed in offspring of C57BKS/J Leprdb /+ and +/+ mice at embryonic day (E)18
      and postnatal day (PN)21 using design-based stereology. Transcutaneous
      measurement of renal function and total glomerular volume were assessed in 6
      month-old offspring. Only +/+ offspring of Leprdb /+ dams were analysed. RESULTS:
      Compared with +/+ dams, Leprdb /+ dams had a 20% and 35% decrease in glucose
      tolerance prior to pregnancy and at E17.5 respectively. Offspring of IGT Leprdb
      /+ dams had approximately 15% fewer nephrons at E18.5 and PN21 than offspring of
      +/+ dams. There was no difference in offspring bodyweight. Despite normal renal
      function, total glomerular volume was 13% greater in 6-month-old offspring of IGT
      Leprdb /+ dams than in +/+ offspring. CONCLUSIONS: IGT throughout gestation
      resulted in a nephron deficit that was established early in renal development.
      Maternal IGT was associated with glomerular hypertrophy in adult offspring,
      likely a compensatory response to maintain normal renal function. Given the
      increasing prevalence of IGT, monitoring glucose from early in gestation may be
      important to prevent altered kidney morphology. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27037900
TI  - Cardiac sarcoidosis.

PMID- 27037901
TI  - Nonpeptidic Selective Inhibitors of the Chymotrypsin-Like (beta5 i) Subunit of
      the Immunoproteasome.
AB  - Elevated expression of the immunoproteasome has been associated with autoimmune
      diseases, inflammatory diseases, and various types of cancer. Selective
      inhibitors of the immunoproteasome are not only scarce, but also almost entirely
      restricted to peptide-based compounds. Herein, we describe nonpeptidic reversible
      inhibitors that selectively block the chymotrypsin-like (beta5i) subunit of the
      human immunoproteasome in the low micromolar range. The most potent of the
      reversibly acting compounds were then converted into covalent, irreversible,
      nonpeptidic inhibitors that retained selectivity for the beta5i subunit. In
      addition, these inhibitors discriminate between the immunoproteasome and the
      constitutive proteasome in cell-based assays. Along with their lack of
      cytotoxicity, these data point to these nonpeptidic compounds being suitable for
      further investigation as beta5i-selective probes for possible application in
      noncancer diseases related to the immunoproteasome.

PMID- 27037902
TI  - Application of multigene phylogenetics and site-stripping to resolve intraordinal
      relationships in the Rhodymeniales (Rhodophyta).
AB  - Previous molecular assessments of the red algal order Rhodymeniales have
      confirmed its monophyly and distinguished the six currently recognized families
      (viz. Champiaceae, Faucheaceae, Fryeellaceae, Hymenocladiaceae, Lomentariaceae,
      and Rhodymeniaceae); however, relationships among most of these families have
      remained unresolved possibly as a result of substitution saturation at deeper
      phylogenetic nodes. The objective of the current study was to improve
      rhodymenialean systematics by increasing taxonomic representation and using a
      more robust multigene dataset of mitochondrial (COB, COI/COI-5P), nuclear (LSU,
      EF2) and plastid markers (psbA, rbcL). Additionally, we aimed to prevent
      phylogenetic inference problems associated with substitution saturation
      (particularly at the interfamilial nodes) by removing fast-evolving sites and
      analyzing a series of progressively more conservative alignments. The
      Rhodymeniales was resolved as two major lineages: (i) the Fryeellaceae as sister
      to the Faucheaceae and Lomentariaceae; and (ii) the Rhodymeniaceae allied to the
      Champiaceae and Hymenocladiaceae. Support at the interfamilial nodes was highest
      when 20% of variable sites were removed. Inclusion of Binghamiopsis,
      Chamaebotrys, and Minium, which were absent in previous phylogenetic
      investigations, established their phylogenetic affinities while assessment of two
      genera consistently polyphyletic in phylogenetic analyses, Erythrymenia and
      Lomentaria, resulted in the proposition of the novel genera Perbella and
      Fushitsunagia. The taxonomic position of Drouetia was reinvestigated with re
      examination of holotype material of D. coalescens to clarify tetrasporangial
      development in this genus. In addition, we added three novel Australian species
      to Drouetia as a result of ongoing DNA barcoding assessments-D. aggregata sp.
      nov., D. scutellata sp. nov., and D. viridescens sp. nov.

PMID- 27037903
TI  - A migraine management training program for primary care providers: An overview of
      a survey and pilot study findings, lessons learned, and considerations for
      further research.
AB  - BACKGROUND: There are five to nine million primary care office visits a year for
      migraine in the United States. However, migraine care is often suboptimal in the
      primary care setting. A prior study indicated that primary care physicians (PCPs)
      wanted direct contact with headache specialists to improve the migraine care they
      provide. OBJECTIVE: We sought to further examine PCPs' knowledge of migraine
      management and assess the feasibility of a multimodal migraine education program
      for PCPs. METHODS: We conducted a survey assessing PCPs' knowledge about
      migraine. We then held three live educational sessions and developed an email
      consultative service for PCPs to submit questions they had about migraine. We
      report both quantitative and qualitative findings. RESULTS: Twenty-one PCPs
      completed the survey. They were generally familiar with the epidemiology of
      migraine (mean prevalence of migraine reported was 12.6% +/- 10.1), the
      psychiatric comorbidities (mean prevalence of comorbid depression was 24.5% +/-
      16.7, mean prevalence of comorbid anxiety was 24.6% +/- 18.3), and evidence-based
      behavioral treatments. Fifty-six percent cited cognitive behavioral therapy, 78%
      cited biofeedback, and 61% cited relaxation therapy as evidence based treatments.
      Though most were aware of the prevalence of psychiatric comorbidities, they did
      not routinely assess for them (43% did not routinely assess for anxiety, 29% did
      not routinely assess for depression). PCPs reported frequently referring patients
      for non-level A evidence based treatments: special diets (60%), acupuncture
      (50%), physical therapy (30%), and psychoanalysis (20%). Relaxation therapy was a
      therapy recommended by 40% of the PCPs. Only 10% reported referring for cognitive
      behavioral therapy or biofeedback. Nineteen percent made minimal or no use of
      migraine preventive medications. Seventy-two percent were unaware of or only
      slightly aware of the American Academy of Neurology guidelines for migraine.
      There was variable attendance at the educational sessions (N=22 at 1st session, 6
      at 2nd session, 15 at 3rd session). Very few PCPs used the email consultative
      service (N=4). CONCLUSIONS: Though PCPs are familiar with many aspects of
      migraine care, there is a need and opportunity for improvement. The three live
      sessions were poorly attended and the email consultative service was rarely used.
      We provide an in depth discussion of targeted areas for educational intervention,
      of the challenges in developing a migraine educational program for PCPs, and
      areas for future study.

PMID- 27037904
TI  - Physical activity, heart rate variability-based stress and recovery, and
      subjective stress during a 9-month study period.
AB  - The aim of this study was to investigate the association between physical
      activity (PA) and objective heart rate variability (HRV)-based stress and
      recovery with subjective stress in a longitudinal setting. Working-age
      participants (n = 221; 185 women, 36 men) were overweight (body mass index, 25.3
      40.1 kg/m2 ) and psychologically distressed (>=3/12 points on the General Health
      Questionnaire). Objective stress and recovery were based on HRV recordings over 1
      3 work days. Subjective stress was assessed with the Perceived Stress Scale and
      PA level with a questionnaire. Data were collected at three time points:
      baseline, 10 weeks post intervention, and at the 36-week follow-up. We adopted a
      latent growth model to investigate the initial level and change in PA, objective
      stress and recovery, and subjective stress at the three measurement time points.
      The results showed that initial levels of PA (P < 0.001) and objective stress (P
      = 0.001) and recovery (P < 0.01) were associated with the change in subjective
      stress. The results persisted after adjustment for intervention group. The
      present results suggest that high PA and objectively assessed low stress and good
      recovery have positive effects on changes in subjective stress in the long-term.

PMID- 27037905
TI  - Primary trabeculotomy compared to combined trabeculectomy-trabeculotomy in
      congenital glaucoma: 3-year study.
AB  - PURPOSE: To compare the outcome of primary trabeculotomy with that of combined
      trabeculectomy-trabeculotomy (CTT) with mitomycin C (MMC) in children with
      congenital glaucoma. METHODS: This is a prospective comparative study, carried
      out on a cohort of 28 eyes (28 infants) with congenital glaucoma. Infants with
      proved congenital glaucoma [based on intra-ocular pressure (IOP), cup/disc (C/D
      ratio), corneal diameter and axial length measurements] were randomly allocated
      to either group A (trabeculotomy) or group B (CTT with MMC). Postoperatively, all
      patients were followed regularly for 3 years; for IOP and C/D evaluation.
      Criteria for successful outcome included resolution of corneal oedema, reversal
      of disc cupping, and IOP 18 mmHg or less. RESULTS: Success rate in each group was
      85.7% (p = 1.00). All preoperative parameters, including horizontal corneal
      diameter, axial length, IOP and C/D ratio, were not statistically significantly
      different between the two groups. Also, postoperative C/D ratio, IOP, IOP
      difference and percentage difference (compared to preoperative values), at
      different follow-up visits, were not statistically significantly different
      between both surgical techniques. Comparing preoperative to postoperative IOP and
      C/D ratio in each group was statistically significant. CONCLUSION: Both primary
      trabeculotomy and CTT with MMC had similar outcomes, which could mean that
      trabeculotomy could be resorted to first.

PMID- 27037906
TI  - Bortezomib-induced pro-inflammatory macrophages as a potential factor limiting
      anti-tumour efficacy.
AB  - Multiple myeloma (MM) is a chronic progressive malignancy of plasma cells.
      Although treatment with the novel proteasome inhibitor, bortezomib, significantly
      improves patient survival, some patients fail to respond due to the development
      of de novo resistance. We have previously shown that cytotoxic drugs can induce
      pro-tumorigenic host-mediated effects which contribute to tumour re-growth and
      metastasis, and thus limit anti-tumour efficacy. However, such effects and their
      impact on tumour cell aggressiveness have not been investigated using cytostatic
      agents such as bortezomib. Here we show that plasma from bortezomib-treated mice
      significantly increases migration, viability and proliferation of MM cells in
      vitro, compared to plasma from vehicle treated mice. In vivo, bortezomib induces
      the mobilization of pro-angiogenic bone marrow cells. Furthermore, mice treated
      with bortezomib and subsequently were used as recipients for an injection of MM
      cells succumb to MM earlier than mice treated with the vehicle. We show that
      bortezomib promotes pro-inflammatory macrophages which account for MM cell
      aggressiveness, an effect which is partially mediated by interleukin-16.
      Accordingly, co-inoculation of MM cells with pro-inflammatory macrophages from
      bortezomib-treated mice accelerates MM disease progression. Taken together, our
      results suggest that, in addition to the known effective anti-tumour activity of
      bortezomib, host-driven pro-tumorigenic effects generated in response to
      treatment can promote MM aggressiveness, and thus may contribute to the overall
      limited efficacy. Copyright (c) 2016 Pathological Society of Great Britain and
      Ireland. Published by John Wiley & Sons, Ltd.

PMID- 27037907
TI  - Technique to Match Gingival Shade when Using Pink Ceramics for Anterior Fixed
      Implant Prostheses.
AB  - Use of pink gingival ceramics can reduce the necessity for extensive surgical
      procedures attempting to restore missing soft and hard tissues in the maxillary
      esthetic zone. Selecting the appropriate shade for pink porcelain poses a
      challenge, especially when the patient presents with a high smile line. This
      paper describes a simple and effective technique to facilitate shade selection
      for gingival ceramics to match the patient's existing gingival shade.

PMID- 27037908
TI  - Determination of RH-5849 and indoxacarb in rice straw, rice husk, brown rice and
      soil using liquid chromatography-tandem triple quadrupole mass spectrometry
      following extraction with QuEChERS method.
AB  - A fast and simple analytical method was developed for the simultaneous
      determination of RH-5849 and indoxacarb in soil, rice straw, rice husk and brown
      rice. QuEChERS (quick, easy, cheap, effective, rugged and safe) method was used
      for extraction, and liquid chromatography with tandem triple quadrupole mass
      spectrometry was used for quantification. The matrix-matched calibration plots
      were linear in the range between 25 and 5000 MUg/L for soil, rice straw, rice
      husk and brown rice samples. All determination coefficients (R(2) ) were
      >=0.9962. The limits of detection and quantification were 1.5 and 5 MUg/kg,
      respectively. Recoveries at three fortification levels ranged between 79.5 and
      97.9% with relative standard deviations <11%. The developed method was validated
      and applied for the analysis of dissipation study samples. For field experiments,
      the half-lives of RH-5849 and indoxacarb in rice straw were 11.93 and 5.83 days,
      respectively. The method was demonstrated to be reliable for the routine
      monitoring of RH-5849 and indoxacarb in rice samples. Copyright (c) 2016 John
      Wiley & Sons, Ltd. 

PMID- 27037909
TI  - Acylated and unacylated ghrelin during OGTT in Prader-Willi syndrome: a rebuttal
      to the conclusions by Kuppens et al.

PMID- 27037910
TI  - Incident and long-term HIV-1 infection among pregnant women in Brazil:
      Transmitted drug resistance and mother-to-child transmission.
AB  - Primary infection, seroconversion, and transmitted drug resistance (TDR) during
      pregnancy may influence the risk of mother-to-child-transmission (MTCT) of HIV-1
      infection. This study estimated recent seroconversion, TDR rates, HIV-1 subtypes
      and pregnancy outcomes among 95 recently diagnosed, antiretroviral (ARV)-naive
      pregnant women recruited during antenatal care in central western Brazil. Recent
      seroconversion was defined by BED-capture enzyme immunoassay (<155 days) and
      ambiguous nucleotides base calls (<1 year) in pol sequences (protease-PR and
      reverse transcriptase-RT regions). TDR was evaluated by the Calibrated Population
      Resistance tool. HIV-1 subtypes were defined by REGA and phylogenetic analyses.
      The median age of participants was 25 years; the median gestational age at
      diagnosis was 20.5 weeks. Based on serology and sequence polymorphism, recent
      infection was identified in 11.6% (11/95) and, 9 of them (82%), probably
      seroconverted during pregnancy; one MTCT case was observed among them. Three
      cases of stillbirth were observed among chronic infected patients (3.6%; 3/84).
      Moderate rate of TDR was observed (9/90, 10%, CI95% 4.7-18.1%). Subtype B was 60%
      (54/90), 13.3% (12/90) was subtype C, 6.7% (6/90) was subtype F1. Recombinant
      B(PR) /F1(RT) and F1(PR) /B(RT) viruses comprised 15.5% (14/90); B(PR) /C(RT)
      mosaics represented 4.4% (4/90). Seroconversion during pregnancy, late
      presentation to antenatal care and moderate TDR identified in this study
      represent significant challenges for the MTCT elimination. J. Med. Virol. 88:1936
      1943, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27037911
TI  - What influences the worldwide genetic structure of sperm whales (Physeter
      macrocephalus)?
AB  - The interplay of natural selection and genetic drift, influenced by geographic
      isolation, mating systems and population size, determines patterns of genetic
      diversity within species. The sperm whale provides an interesting example of a
      long-lived species with few geographic barriers to dispersal. Worldwide mtDNA
      diversity is relatively low, but highly structured among geographic regions and
      social groups, attributed to female philopatry. However, it is unclear whether
      this female philopatry is due to geographic regions or social groups, or how this
      might vary on a worldwide scale. To answer these questions, we combined mtDNA
      information for 1091 previously published samples with 542 newly obtained DNA
      profiles (394-bp mtDNA, sex, 13 microsatellites) including the previously
      unsampled Indian Ocean, and social group information for 541 individuals. We
      found low mtDNA diversity (pi = 0.430%) reflecting an expansion event <80 000
      years bp, but strong differentiation by ocean, among regions within some oceans,
      and among social groups. In comparison, microsatellite differentiation was low at
      all levels, presumably due to male-mediated gene flow. A hierarchical amova
      showed that regions were important for explaining mtDNA variance in the Indian
      Ocean, but not Pacific, with social group sampling in the Atlantic too limited to
      include in analyses. Social groups were important in partitioning mtDNA and
      microsatellite variance within both oceans. Therefore, both geographic philopatry
      and social philopatry influence genetic structure in the sperm whale, but their
      relative importance differs by sex and ocean, reflecting breeding behaviour,
      geographic features and perhaps a more recent origin of sperm whales in the
      Pacific. By investigating the interplay of evolutionary forces operating at
      different temporal and geographic scales, we show that sperm whales are perhaps a
      unique example of a worldwide population expansion followed by rapid assortment
      due to female social organization.

PMID- 27037912
TI  - GAMDB: a web resource to connect microRNAs with autophagy in gerontology.
AB  - OBJECTIVES: MicroRNAs (miRNAs) are endogenous ~23 nucleotides (nt) RNAs,
      regulating gene expression by pairing to the mRNAs of protein-coding genes to
      direct their post-transcriptional repression. Both in normal and aberrant
      activities, miRNAs contribute to a recurring paradigm of cellular behaviors in
      pathological settings, especially in gerontology. Autophagy, a multi-step
      lysosomal degradation process with function to degrade long-lived proteins and
      damaged organelles, has significant impact on gerontology. Thus, elucidating how
      miRNAs participate in autophagy may enlarge the scope of miRNA in autophagy and
      facilitate researches in gerontology. MATERIALS AND METHODS: Herein, based upon
      the published studies, predicted targets and gerontology-related diseases, we
      constructed a web resource named Gerontology-Autophagic-MicroRNA Database (GAMDB)
      (http://gamdb.liu-lab.com/index.php), which contained 836 autophagy-related
      miRNAs, 197 targeted genes/proteins and 56 aging-related diseases such as
      Parkinson' disease, Alzheimer's disease and Huntington's disease. RESULTS AND
      CONCLUSION: We made use of large amounts of data to elucidate the intricate
      relationships between microRNA-regulated autophagic mechanisms and gerontology.
      This database will facilitate better understanding of autophagy regulation
      network in gerontology and thus promoting gerontology-related therapy in the
      future.

PMID- 27037913
TI  - Electrogram Characteristics of Ablated and Non-Ablated Myocardium in Humans: A
      Comparison of Miniaturized Embedded Electrodes and Conventional Ablation
      Electrodes.
AB  - INTRODUCTION: Intracardiac electrogram voltage remains an important metric for
      radiofrequency lesion application. Embedded micro-electrodes within ablation
      catheters are now approved for use in humans. OBJECTIVE: This study examined
      electrogram characteristics of miniaturized electrode bipoles (iEGMmini )
      compared to distal ablation tip bipoles (iEGMstandard ) in the setting of typical
      atrial flutter in humans. METHODS: This was a single-center prospective trial
      involving 21 patients. A total of 54 non-ablated and 56 ablated sites were
      analyzed offline by separate blinded observers for iEGM voltage after a
      clinically successful radiofrequency (RF) ablation for typical atrial flutter.
      Ablation sites were defined as sites that were localized anatomically within the
      RF lesion set and did not have atrial capture at 10 mA and 2 milliseconds. Non
      ablated sites were defined as sites adjacent to or remote from the ablation
      lesion set with capture at 10 mA and 2 milliseconds. RESULTS: iEGMmini had
      greater voltages at non-ablated sites and lower voltages at ablated sites than
      iEGMstandard (non-ablated sites iEGMstandard 0.64 mV vs. iEGMmini 1.0 mV; ablated
      sites iEGMstandard 0.15 mV, iEGMmini 0.08 mV, P < 0.001). The difference for each
      patient between ablated and non-ablated sites was greater for iEGMmini compared
      to iEGMstandard (0.94 mV +/- 0.57 iEGMmini vs. 0.52 mV +/- 0.35 iEGMstandard , P
      < 0.001). Inter-observer agreement was good among all non-ablated sites and
      iEGMmini ablated sites, but was less robust for ablated sites using iEGMstandard
      . CONCLUSIONS: Imbedded mini-electrode iEGM bipoles had higher voltages in non
      ablated tissue, lower voltages in ablated tissue, and significantly greater intra
      patient differences between ablated and non-ablated sites. These data suggest a
      potential role for miniaturized electrode bipole use in RF lesion monitoring.

PMID- 27037914
TI  - Primary rectal mucosa-associated lymphoid tissue lymphoma in a patient with
      previously identified primary biliary cirrhosis and secondary Sjogren's syndrome.
AB  - An 83-year-old female began treatment with prednisolone and ursodeoxycholic acid
      at 62 years of age, following a diagnosis of primary biliary cirrhosis (PBC) and
      secondary Sjogren's syndrome (SjS). With persisting bloody stools, the patient
      underwent colonoscopy at 83 years of age. Histopathological evaluation revealed
      mucosa-associated lymphoid tissue (MALT) lymphoma. The elevated rectal lesion
      resolved with rituximab treatment. We report this case because although patients
      with SjS are at increased risk of malignant lymphoma, primary rectal MALT
      lymphoma is very uncommon in association with PBC and secondary SjS. 

PMID- 27037915
TI  - Estimation of average causal effect using the restricted mean residual lifetime
      as effect measure.
AB  - Although mean residual lifetime is often of interest in biomedical studies,
      restricted mean residual lifetime must be considered in order to accommodate
      censoring. Differences in the restricted mean residual lifetime can be used as an
      appropriate quantity for comparing different treatment groups with respect to
      their survival times. In observational studies where the factor of interest is
      not randomized, covariate adjustment is needed to take into account imbalances in
      confounding factors. In this article, we develop an estimator for the average
      causal treatment difference using the restricted mean residual lifetime as target
      parameter. We account for confounding factors using the Aalen additive hazards
      model. Large sample property of the proposed estimator is established and
      simulation studies are conducted in order to assess small sample performance of
      the resulting estimator. The method is also applied to an observational data set
      of patients after an acute myocardial infarction event.

PMID- 27037916
TI  - Aroused at Home: Basic Autonomic Regulation during Orthostatic and Physical
      Activation is Altered in Children with Social Anxiety Disorder.
AB  - Previous research has documented altered autonomic nervous system (ANS)
      reactivity to laboratory-based social stress tasks in children with social
      anxiety disorder (SAD). It is unclear, however, whether these alterations are
      caused by the unfamiliar and possibly threatening lab environment or whether they
      generalize to other, more representative contexts. Sympathetic and
      parasympathetic autonomic functioning was assessed in the home (minimizing
      environmental threat) during a supine baseline phase and two physical activation
      phases (orthostatic stress, stair stepping) in children (9-13 years) with SAD (n
      = 27) and healthy control children (n = 27). Relative to controls, children with
      SAD showed tonic autonomic hyperarousal as indicated by higher heart rate and
      electrodermal activity during the supine baseline phase. Further, there was
      evidence for stronger cardiac and vascular sympathetic reactivity (T-wave
      amplitude, pulse wave transit time) to moderate physical activation in children
      with SAD. Higher autonomic arousal during rest was related to measures of trait
      social anxiety and general psychopathology. Groups did not differ on
      parasympathetic parameters. Our results extend previous laboratory findings and
      provide the first evidence for alterations in children with SAD during basal
      autonomic regulation and in the absence of explicit social evaluative threat.
      They may further help to clarify conflicting study results from previous
      laboratory studies. The findings underline the importance of psychophysiological
      assessment using different environments and tasks to elucidate the physiological
      bases of SAD.

PMID- 27037917
TI  - Contribution of (18)F-FDG PET in the diagnostic assessment of fever of unknown
      origin (FUO): a stratification-based meta-analysis.
AB  - PURPOSE: The aim of this study was to quantify the contribution of FDG PET to the
      diagnostic assessment of fever of unknown origin (FUO), taking into account the
      diagnostic limitations resulting from the composite nature of this entity.
      METHODS: The PubMed/MEDLINE database was searched from 2000 to September 2015.
      Original articles fulfilling the following criteria were included: (1) FUO as the
      initial diagnosis, (2) no immunosuppressed or nosocomial condition, (3) final
      diagnosis not based on PET, (4) a follow-up period specified, (5) adult
      population, and (6) availability of adapted data for calculation of odds ratios
      (ORs). ORs were computed for each study and then pooled using a random effects
      model. Stratification-based sensitivity analyses were finally performed using the
      following prespecified criteria: (a) study design, (b) PET device, (c) geographic
      area, and (d) follow-up period. RESULTS: A meta-analysis of the 14 included
      studies showed that normal PET findings led to an increase in the absolute final
      diagnostic rate of 36 % abnormal PET findings to an increase of 83 %,
      corresponding to a pooled OR of 8.94 (95 % CI 4.18 - 19.12, Z = 5.65; p <
      0.00001). The design of the studies influenced the results (OR 2.92, 95 % CI 1.00
      - 8.53 for prospective studies; OR 18,57, 95 % CI 7.57 - 45.59 for retrospective
      studies; p = 0.01), whereas devices (dedicated or hybrid), geographic area and
      follow-up period did not. CONCLUSION: Abnormal PET findings are associated with a
      substantially increased final diagnostic rate in FUO. Consequently, FDG PET could
      be considered for inclusion in the first-line diagnostic work-up of FUO. Further
      randomized prospective studies with standardized FDG PET procedures are warranted
      to confirm this first-line position.

PMID- 27037918
TI  - Double plate fixation for the management of proximal interphalangeal joint
      instability in 30 horses (1987-2015).
AB  - REASONS FOR PERFORMING STUDY: Double plate fixation has been reported in a small
      number of horses with comminuted fractures of the middle phalanx. There are no
      published reports using this technique in the management of other injuries that
      destabilise the proximal interphalangeal joint (PIJ), including biaxial
      palmar/plantar eminence fractures and disruption of the palmar/plantar soft
      tissue support structures of the PIJ. Furthermore, there is a paucity of
      information on the long-term prognosis for horses undergoing double plate
      fixation to manage destabilising injuries of the PIJ. OBJECTIVES: To document
      further the clinical use of double plate fixation for management of injuries to
      the PIJ resulting in palmar/plantar instability and compare these results with
      other methods of management. STUDY DESIGN: Retrospective case series. METHODS:
      The case records and radiographs of 30 horses with destabilising injuries to the
      PIJ treated by double plate fixation at Texas A&M University between 1987 and
      2013 were analysed. Long-term follow-up information was obtained by telephone
      interview with the client or referring veterinarian. RESULTS: Thirty-one
      disruptive PIJ injuries were double plated in 30 cases. Twenty-nine of 30 horses
      were discharged from the hospital. The medial time for post operative external
      coaptation was 41 days. Long-term follow-up (>2 years) was available for 25
      horses, of which 15 (60%) returned to useful function. Radiographic evidence of
      fracture healing and arthrodesis of the PIJ was evident in 28 (90%) repairs at 6
      months following repair. CONCLUSIONS: The use of 2 abaxially placed dorsal plates
      for management of destabilising injuries to the PIJ results in a very good
      prognosis for survival and a reasonable prognosis for return to functional use.

PMID- 27037919
TI  - Discussing reproductive health in spinal care, part II: fertility issues.
AB  - PURPOSE: Due to advancing insights, discussing fertility in spinal care is an
      emerging topic. Studies among neurosurgeons to evaluate clinical practice about
      discussing fertility are non-existent. The aim of this study is to review
      knowledge, attitude and practice patterns regarding discussing fertility in
      spinal care. METHODS: Dutch neurosurgeons and residents were sent a mail-based
      questionnaire addressing attitude, knowledge and practice patterns regarding
      discussing fertility. RESULTS: Response rate was 62 % (compared to mean of 28 %
      in similar surveys) with 89 questionnaires suitable for analysis. Mean age was 42
      years with 83 % of respondents being male. A quarter of respondents stated
      neurosurgeons are responsible to discuss fertility, with 12 % indicating to
      actually do this. Fertility is discussed more often with patients with cauda
      equina syndrome (70 %) and with men (p = 0.006). Merely 8 % of respondents stated
      to have adequate knowledge on fertility preservation (FP); this percentage was
      higher for doctors with spinal surgery as specialty (p = 0.015). In case of cauda
      equina syndrome, doctors with more knowledge discussed fertility more often (p =
      0.002). Fifty-three percent of neurosurgeons wished to enhance their knowledge,
      in order to feel more comfortable to discuss fertility with their patients. Five
      percent indicated to have ever referred a patient to a fertility specialist.
      CONCLUSION: With the exception of cauda equina syndrome, fertility is not
      routinely discussed in spinal care. Fertility is discussed more often with men.
      Recent guidelines state that discussing fertility is an essential part of good
      practice in spinal care. Education on fertility and FP needs to be integrated in
      the neurosurgical training program to create more awareness, and to enable
      clinicians to provide adequate information and care to the patient.

PMID- 27037920
TI  - The role of specialist units to provide focused care and complication avoidance
      following traumatic spinal cord injury: a systematic review.
AB  - OBJECTIVE: Current recommendations for traumatic spinal cord injury treatment
      recommend immediate transfer to a spinal injury unit (SIU) where available
      following patient stabilisation. Although transfer is dependent on a variety of
      factors, the largest review was unable to justify implementation of such units on
      the basis of insufficient and lack of quality data in favour of care at the SIU
      as opposed to non-SIU centres. Our study sought to investigate: are subspecialty
      spinal injury units (SIUs) able to provide superior care compared with
      traditional trauma/rehab units? Is the standard of care of acute spinal cord
      injured patients to be managed in SIU's? METHOD: A literature search was
      conducted across five major databases using the key terms: "spinal cord injury"
      AND "Spinal Injury Unit" OR "spinal rehabilitation" OR "spinal injury centre" OR
      "specialist care" OR "care requirements." RESULTS: After review of over 500
      studies, only 9 met inclusion criteria, 3 of which were past reviews. There were
      no relevant RCT's obtained. Standardised roles of global SIU units are needed to
      deliver equitable and high quality care as current evidence demonstrates variable
      standards of care and service (mean LOS range: 16-174 days). There is low quality
      evidence supporting earlier admission into SIU units being associated with
      improved neurological outcome, complication rates and reduced LOS, despite
      variations in the definition of "early admission" across studies. CONCLUSIONS:
      Our review demonstrates a lack of standardisation within SIU on a global scale,
      with significantly different outcomes reported across published studies. New and
      higher quality evidence directly comparing SIU to non-SIU based care is required.
      Earlier transfer (<24 h) to SIU following initial injury and stabilisation is
      advised.

PMID- 27037921
TI  - Development of an ex vivo cavity model to study repair strategies in loaded
      intervertebral discs.
AB  - PURPOSE: The aim of this study was to compare two approaches for the delivery of
      biomaterials to partially nucleotomised intervertebral discs in whole organ
      culture under loading. Such models can help to bridge the gap between in vitro
      and in vivo studies by assessing (1) suitability of biomaterial delivery and
      defect closure methods, (2) effect of mechanical loading and (3) tissue response.
      METHODS: Mechanical performance of bovine discs filled with a hyaluronan-based
      thermoreversible hydrogel delivered through the annulus fibrosus (AF) or the bony
      endplate (EP) was evaluated under cyclic axial loading in a bioreactor. The
      loading protocol was optimised to achieve physiological disc height changes in
      nucleotomised discs. A loading regime of 0.06 +/- 0.02 MPa, 0.1 Hz, 6 h daily was
      applied on the nucleotomised discs. Disc height and stiffness were tracked for 5
      days, followed by histological analyses. RESULTS: Creation of a defect is less
      demanding for AF approach, while sealing is superior with the EP approach.
      Dynamic compressive stiffness is reduced following nucleotomy, with no
      significant difference between the two approaches. Disc height loss was higher,
      disc height recovery was lower and region around the defect with reduced cell
      viability was smaller for AF-approached than EP-approached discs. CONCLUSIONS:
      Two alternative methods for biomaterial testing in whole organ culture under
      loading were developed. Such models bring insights on the ability of the
      biomaterial to restore the mechanical behaviour of the discs. From a clinical
      perspective, the cavity models can simulate treatment of nucleotomy after disc
      herniation in young patients, whereby the remaining nucleus pulposus is still
      functional and therefore at high risk of re-herniation, though the defect may
      differ from the clinical situation.

PMID- 27037922
TI  - Ornithine Aminotransferase Deficiency in Differential Diagnosis of Neonatal
      Hyperammonemia: A Case with a Novel OAT Gene Mutation.

PMID- 27037923
TI  - Clinical Profile of Atypical Manifestations of Dengue Fever: Author's Reply.

PMID- 27037924
TI  - Formulation and evaluation of self-emulsifying orlistat tablet to enhance drug
      release and in vivo performance: factorial design approach.
AB  - The purpose of the present research work was to formulate, evaluate, and optimize
      self-emulsifying orlistat tablet to enhance drug release followed by in vivo
      antiobesity activity in Wistar rats. Initially, the solubility of orlistat was
      determined in different natural oils, surfactant, and co-surfactants. Self
      emulsifying drug delivery system (SEDDS) was prepared by using castor oil, Tween
      80, and Capryol PGMC as components. Liquid SEDDS evaluated for globule size and
      emulsification time. A 3(2) full factorial design was utilized for the
      optimization purpose. Formulation variables such as quantity of oil (X1) and
      ratio of surfactant to co-surfactant (X2) were investigated for their effect on
      globule size and emulsification time. Optimized formulation with minimum globule
      size was freeze-dried which further compressed into the tablet. Finally,
      optimized formulation evaluated for the in vitro drug release study followed by
      weight losing potential in Wistar rats. Globule size and emulsification time for
      the optimized formulation were found to be 96.4 +/- 8.5 nm and 26 +/- 4 s,
      respectively. Fourier transform infra red spectroscopy (FTIR) studies indicated
      that there was no interaction between drug and excipients. Differential scanning
      calorimetry (DSC) and X-ray diffraction (XRD) study revealed that there was the
      conversion of crystalline orlistat to the amorphous form. Orlistat release from
      the self-emulsifying tablet formulation was faster with higher weight reduction
      potential in Wistar rats than the marketed formulation. Increased in vitro drug
      release with considerable in vivo weight loss by self-emulsifying tablet suggests
      that the SEDDS could serve as potential formulation strategy for orlistat.

PMID- 27037925
TI  - Colonization and diversification in the African 'sky islands': insights from
      fossil-calibrated molecular dating of Lychnis (Caryophyllaceae).
AB  - The flora on the isolated high African mountains or 'sky islands' is remarkable
      for its peculiar adaptations, local endemism and striking biogeographical
      connections to remote parts of the world. Ages of the plant lineages and the
      timing of their radiations have frequently been debated but remain contentious as
      there are few estimates based on explicit models and fossil-calibrated molecular
      clocks. We used the plastid region maturaseK (matK) and a Caryophylloflora
      paleogenica fossil to infer the age of the genus Lychnis, and constructed a data
      set of three plastid (matK; a ribosomal protein S16 (rps16); and an intergenic
      spacer (psbE-petL)) and two nuclear (internal transcribed spacer (ITS) and a
      region spanning exon 18-24 in the second largest subunit of RNA polymerase II
      (RPB2)) loci for joint estimation of the species tree and divergence time of the
      African representatives. The time of divergence of the African high-altitude
      Lychnis was placed in the late Miocene to early Pliocene. A single speciation
      event was inferred in the early Pliocene; subsequent speciation took place
      sporadically from the late Pliocene to the middle Pleistocene. We provide further
      support for a Eurasian origin of the African 'sky islands' floral elements, which
      seem to have been recruited via dispersals at different times: some old, as in
      Lychnis, and others very recent. We show that dispersal and diversification
      within Africa play an important role in shaping these isolated plant communities.

PMID- 27037926
TI  - Erratum to: Design of Polyepitope DNA Vaccine against Breast Carcinoma Cells and
      Analysis of Its Expression in Dendritic Cells.

PMID- 27037927
TI  - Strained GaAs/InGaAs Core-Shell Nanowires for Photovoltaic Applications.
AB  - We report on the successful growth of strained core-shell GaAs/InGaAs nanowires
      on Si (111) substrates by molecular beam epitaxy. The as-grown nanowires have a
      density in the order of 10(8) cm(-2), length between 3 and 3.5 MUm, and diameter
      between 60 and 160 nm, depending on the shell growth duration. By applying a
      range of characterization techniques, we conclude that the In incorporation in
      the nanowires is on average significantly smaller than what is nominally expected
      based on two-dimensional growth calibrations and exhibits a gradient along the
      nanowire axis. On the other hand, the observation of sharp dot-like emission
      features in the micro-photoluminescence spectra of single nanowires in the 900
      1000-nm spectral range highlights the co-existence of In-rich enclosures with In
      content locally exceeding 30 %. 

PMID- 27037928
TI  - Percutaneous closure of an incomplete left atrial appendage closure.

PMID- 27037929
TI  - Readmission in Cirrhosis: a Growing Problem.
AB  - OPINION STATEMENT: Patients with cirrhosis are at risk for several complications
      that require readmission. Readmissions are a direct burden on the patient and the
      family and are associated with negative outcomes to the patient, family, and
      health care system. Several recent studies have shown a high rate of readmission
      in patients with cirrhosis and a trend towards an increase in cost of health care
      delivery. Physicians and hospitals should recognize the patient at high risk for
      readmission not only at dismissal from hospital but also at admission. The Model
      for End-Stage Liver Disease (MELD) score may be used as a tool for risk
      stratification for readmission among patient with cirrhosis. Frailty,
      comorbidity, socioeconomic status, and type of health care delivery system are
      probable independent risk factors. Strategies to prevent readmission should
      target the high-risk patient.

PMID- 27037930
TI  - The Changing Role of Sodium Management in Cirrhosis.
AB  - OPINION STATEMENT: Hyponatremia may occur in patients with cirrhosis and ascites
      mainly due to water retention and an inability of the kidney to excrete free
      water. The main reason for this abnormality is related to the fact that these
      patients have portal hypertension and this leads to systemic vasodilation that in
      turn activates sodium-retaining and water-retaining systems such as the renin
      angiotensin-aldosterone system and arginine vasopressin (AVP). AVP increases
      solute-free water retention by acting on the V2 receptors of the kidney
      collecting tubes. Hyponatremia in cirrhosis is defined as a serum sodium level
      less than 130 meq/L. The appearance of hyponatremia in patients with advanced
      cirrhosis portends a poor prognosis before and after liver transplantation.
      Treatment of hyponatremia is difficult; fluid restriction rarely increases serum
      sodium levels and other therapies are associated with important drawbacks. A
      thorough discussion of the underlying mechanisms leading to hyponatremia and
      hypernatremia in cirrhosis and current treatment options including the use of
      vaptans (V2 receptor antagonists) are discussed in this review.

PMID- 27037932
TI  - Echo-level compensation and delay tuning in the auditory cortex of the mustached
      bat.
AB  - During echolocation, bats continuously perform audio-motor adjustments to
      optimize detection efficiency. It has been demonstrated that bats adjust the
      amplitude of their biosonar vocalizations (known as 'pulses') to stabilize the
      amplitude of the returning echo. Here, we investigated this echo-level
      compensation behaviour by swinging mustached bats on a pendulum towards a
      reflective surface. In such a situation, the bats lower the amplitude of their
      emitted pulses to maintain the amplitude of incoming echoes at a constant level
      as they approach a target. We report that cortical auditory neurons that encode
      target distance have receptive fields that are optimized for dealing with echo
      level compensation. In most cortical delay-tuned neurons, the echo amplitude
      eliciting the maximum response matches the echo amplitudes measured from the
      bats' biosonar vocalizations while they are swung in a pendulum. In addition,
      neurons tuned to short target distances are maximally responsive to low pulse
      amplitudes while neurons tuned to long target distances respond maximally to high
      pulse amplitudes. Our results suggest that bats dynamically adjust biosonar pulse
      amplitude to match the encoding of target range and to keep the amplitude of the
      returning echo within the bounds of the cortical map of echo delays.

PMID- 27037933
TI  - Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90
      Inhibitors.
AB  - Development of heat shock protein 90 (Hsp90) C-terminal inhibitors has emerged as
      an exciting strategy for the treatment of cancer. Previous efforts have focused
      on modifications to the natural products novobiocin and coumermycin. Moreover,
      variations in both the sugar and amide moieties have been extensively studied,
      whereas replacements for the coumarin core have received less attention. Herein,
      24 cores were synthesized with varying distances and angles between the sugar and
      amide moieties. Compounds that exhibited good anti-proliferative activity against
      multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed
      the sugar and amide moieties between 7.7 and 12.1 A apart along with angles of
      180 degrees .

PMID- 27037934
TI  - Physical and Bioactive Properties of Muffins Enriched with Raspberry and
      Cranberry Pomace Powder: A Promising Application of Fruit By-Products Rich in
      Biocompounds.
AB  - The objective of this study was to determine the effects on quality of
      incorporating raspberry and cranberry pomaces into American-style muffins
      prepared under various baking conditions. The different baking conditions did not
      affect the texture or microstructure of the control muffins. The enhanced samples
      baked at 140  degrees C for 30 min were characterized by a harder texture than
      the control muffins and by a distributed protein matrix and distorted starch
      granules, while those baked at 240  degrees C for 15 min had a moist texture and
      showed incomplete starch gelatinization. The mean percent recovery of ellagic
      acid, flavonols, tocopherols, tocotrienols, and anthocyanins after baking were
      156, 53, 48, 43, and 22 %, respectively. Lower baking temperature was better for
      ellagic acid and tocotrienols, but worse for flavonols, tocopherols, and
      anthocyanins. It seems that, for the enhanced samples, the intermediate baking
      conditions (180  degrees C for 20 min) guarantee the best microstructure and
      texture and the appropriate retention of phytochemicals in muffins. 

PMID- 27037935
TI  - Differential response of ammonia-oxidizing archaea and bacteria to the wetting of
      salty arid soil.
AB  - Ammonia-oxidizing archaea and bacteria (AOA, AOB) catalyze the first and rate
      limiting step of nitrification. To examine their differential responses to the
      wetting of dry and salty arid soil, AOA and AOB amoA genes (encoding subunit A of
      the ammonia monooxygenase) and transcripts were enumerated in dry (summer) and
      wet (after the first rainfall) soil under the canopy of halophytic shrubs and
      between the shrubs. AOA and AOB were more abundant under shrub canopies than
      between shrubs in both the dry and wetted soil. Soil wetting caused a significant
      decrease in AOB abundance under the canopy and an increase of AOA between the
      shrubs. The abundance of the archaeal amoA gene transcript was similar for both
      the wet and dry soil, and the transcript-to-gene ratios were < 1 independent of
      niche or water content. In contrast, the bacterial amoA transcript-to-gene ratios
      were between 78 and 514. The lowest ratio was in dry soil under the canopy and
      the highest in the soil between the shrubs. The results suggest that the AOA are
      more resilient to stress conditions and maintain a basic activity in arid
      ecosystems, while the AOB are more responsive to changes in the biotic and
      abiotic conditions. 

PMID- 27037936
TI  - Diagnostic and prognostic factors for acute encephalopathy.
AB  - BACKGROUND: Acute encephalopathy has the possibility of sequelae. While early
      treatment is required to prevent the development of sequelae, differential
      diagnosis is of the utmost priority. The aim of this study was therefore to
      identify parameters that can facilitate early diagnosis and prediction of outcome
      of acute encephalopathy. METHODS: We reviewed the medical charts of inpatients
      from 2005 to 2011 and identified 33 patients with febrile status epilepticus.
      Subjects were classified into an acute encephalopathy group (n = 20) and a
      febrile convulsion group (n = 13), and the parameters serum aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase
      (LDH), ammonia (NH3 ), cerebrospinal fluid (CSF) tau protein, and CSF interleukin
      6 compared between them. Furthermore, the relationship between each parameter and
      prognosis was investigated in the encephalopathy group. RESULTS: Significant
      differences in serum AST, ALT, and LDH were observed between the febrile
      convulsion and acute encephalopathy group. Moreover, a significant difference in
      serum LDH was noted between the patients with and without developmental
      regression at the time of hospital discharge in the encephalopathy group. In
      particular, CSF tau protein was found to be highly likely to indicate progress,
      with CSF tau protein >1000 pg/dL associated with poor prognosis leading to
      developmental regression. CONCLUSION: Serum AST, ALT and LDH may be related to
      early diagnosis and prognosis, and should be carefully investigated in patients
      with encephalopathy. CSF tau protein could also be used as an indicator of poor
      prognosis in acute encephalopathy.

PMID- 27037937
TI  - Threshold dose for discrimination of nicotine via cigarette smoking.
AB  - RATIONALE: The lowest nicotine threshold "dose" in cigarettes discriminated from
      a cigarette containing virtually no nicotine may help inform the minimum dose
      maintaining dependence. OBJECTIVES: Spectrum research cigarettes (from NIDA)
      differing in nicotine content were used to evaluate a procedure to determine
      discrimination thresholds. METHODS: Dependent smokers (n = 18; 13 M, 5 F) were
      tested on ability to discriminate cigarettes with nicotine contents of 11, 5,
      2.4, and 1.3 mg/g, one per session, from the "ultralow" cigarette with 0.4 mg/g,
      after having discriminated 16 mg/g from 0.4 mg/g (all had 9-10 mg "tar").
      Exposure to each was limited to 4 puffs/trial. All subjects were abstinent from
      smoking overnight prior to each session, and the number of sessions was
      determined by the participant's success in discrimination behavior on >80 % of
      trials. Subjective perceptions and behavioral choice between cigarettes were also
      assessed and related to discrimination behavior. RESULTS: The median threshold
      was 11 mg/g, but the range was 2.4 to 16 mg/g, suggesting wide variability in
      discrimination threshold. Compared to the ultralow, puff choice was greater for
      the subject's threshold dose but only marginal for the subthreshold (next lowest
      nicotine) cigarette. Threshold and subthreshold also differed on subjective
      perceptions but not withdrawal relief. CONCLUSIONS: Under these testing
      conditions, threshold content for discriminating nicotine via cigarettes may be
      11 mg/g or greater for most smokers, but some can discriminate nicotine contents
      one-half or one-quarter this amount. Further study with other procedures and
      cigarette exposure amounts may identify systematic differences in nicotine
      discrimination thresholds.

PMID- 27037938
TI  - The natural expression of individual differences in self-reported level of
      response to alcohol during ecologically assessed drinking episodes.
AB  - RATIONALE: Low sensitivity to alcohol is a well-established risk factor for
      alcohol use disorder (AUD). However, little is known about how the low
      sensitivity phenotype is expressed on a fine-grained, momentary level in
      drinkers' daily experience. OBJECTIVES: The objective of the study is to evaluate
      individual differences in subjective states and appraisals of alcoholic beverages
      during the ascending limb of real-world drinking episodes. METHODS: Social
      drinkers (N = 398) with varying degrees of alcohol sensitivity as indexed by the
      Self-Rating of the Effects of Alcohol form (SRE; Schuckit et al. in Addiction
      92:979-988, 1997a) recorded diary entries over a 3-week monitoring period (2576
      drinking episodes containing 6546 moments). Hierarchical linear modeling was used
      to evaluate whether individual differences in alcohol sensitivity predicted
      differing intra-episode estimated blood alcohol concentration (eBAC)
      trajectories, ratings of subjective states, and drink appraisals. RESULTS: Lower
      self-reported alcohol sensitivity was associated with consuming "too much, too
      fast," as indicated by a steeper slope of ascending eBAC. In models adjusted for
      momentary eBAC level, participants reporting lower alcohol sensitivity at
      baseline showed blunted subjective intoxication and drink-contingent punishment.
      CONCLUSIONS: The results suggest that low sensitivity to alcohol is associated
      with a blunting of some forms of subjective feedback (i.e., perceptions of
      intoxication and punishment) that might typically encourage drinking restraint.
      This may 'tip the scales' toward excess consumption and could help to explain why
      a low alcohol sensitivity forecasts AUD.

PMID- 27037939
TI  - Chronic methamphetamine self-administration alters cognitive flexibility in male
      rats.
AB  - RATIONALE: Methamphetamine (meth) addiction is a chronically relapsing disorder
      that often produces persistent cognitive deficits. These include decreased
      cognitive flexibility, which may prevent meth addicts from altering their
      habitual drug abuse and leave them more susceptible to relapse. Multiple factors
      including low rates of compliance with research study participation and varied
      drug use patterns make the relationship between cognitive flexibility and relapse
      difficult to establish in clinical populations. OBJECTIVES: Here, we combined an
      extended-access meth self-administration paradigm with an automated set-shifting
      task in rats to directly compare cognitive flexibility performance with meth
      seeking behavior. METHODS: Rats were pre-trained on an automated visual
      discrimination task, followed by 14 days of extended access (6 h/day) of meth or
      sucrose self-administration. They were then tested in the set-shifting task on
      strategy shift and reversal and subsequently assessed for cue-induced
      reinstatement of meth seeking. RESULTS: Rats with a history of meth, but not
      sucrose, self-administration had selective deficits in reversal learning.
      Specifically, meth rats had an increase in the total number of errors and
      perseverative errors (corresponding to the old stimulus-reward association)
      following the reversal shift, which correlated with prior stable meth self
      administration. However, no relationship was seen between errors during the
      reversal and cue-induced reinstatement. CONCLUSION: The lack of association
      between meth-induced reversal deficits and cue-induced reinstatement to meth
      seeking indicates that these two domains may constitute independent pathologies
      of meth addiction.

PMID- 27037940
TI  - Can metronomic maintenance with weekly vinblastine prevent early
      relapse/progression after bevacizumab-irinotecan in children with low-grade
      glioma?
AB  - The association of bevacizumab and irinotecan has been shown to display a quick
      efficacy in low-grade glioma (LGG), but most patients relapse within months after
      cessation of therapy. From October 2012 to March 2014, four patients have been
      treated with irinotecan-bevacizumab followed by a metronomic maintenance with
      weekly vinblastine to try to prevent relapses. After a median follow-up of 23
      months after the end of the bevacizumab-irinotecan induction, no patient
      relapsed. These observations suggest that maintenance chemotherapy with weekly
      vinblastine after an induction by irinotecan-bevacizumab can improve progression
      free survival in children with LGG.

PMID- 27037941
TI  - Hexagonal gradient scheme with RF spoiling improves spoiling performance for high
      flip-angle fast gradient echo imaging.
AB  - PURPOSE: To present a framework in which time-varying gradients are applied with
      RF spoiling to reduce unwanted signal, particularly at high flip angles. METHODS:
      A time-varying gradient spoiler scheme compatible with RF spoiling is defined, in
      which spoiler gradients cycle through the vertices of a hexagon, which we call
      hexagonal spoiling. The method is compared with a traditional constant spoiling
      gradient both in the transition to and in the steady state. Extended phase graph
      (EPG) simulations, phantom acquisitions, and in vivo images were used to assess
      the method. RESULTS: Simulations, phantom and in vivo experiments showed that
      unwanted signal was markedly reduced by employing hexagonal spoiling, both in the
      transition to and in the steady state. For adipose tissue at 1.5 Tesla, the
      unwanted signal in the steady state with a 60  degrees  flip angle was reduced
      from 22% with constant spoiling to 2% with hexagonal spoiling. CONCLUSIONS: A
      time-varying gradient spoiler scheme that works with RF spoiling, called
      "hexagonal spoiling," has been presented and found to offer improved spoiling
      over the traditional constant spoiling gradient. Magn Reson Med 77:1231-1237,
      2017. (c) 2016 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 License, which permits use, distribution and reproduction in any
      medium, provided the original work is properly cited.

PMID- 27037948
TI  - Helpful and unhelpful responses after suicide: Experiences of bereaved family
      members.
AB  - Individuals who are bereaved by suicide and other traumatic natured deaths are
      thought to be at greater risk of psychological complications, than people
      bereaved by other means. While it is recognized that interventions can influence
      the bereavement process, there remains limited communications about both helpful
      responses and those that may adversely influence the grieving process for the
      suicide bereaved. This paper presents findings from a narrative study, which
      sought the experiences of family members after the loss of a loved one as a
      result of suicide. The study findings demonstrated that responses by agencies are
      often insensitive and not aligned with the needs of those bereaved. We argue that
      training is paramount for all services to increase awareness of the needs of
      people bereaved by suicide and available support services. Changes to
      organizational policies in relation to finance support would greatly support the
      bereaved during their time of grief and heightened distress. 

PMID- 27037949
TI  - Tryptophan Hydroxylase 1 Variant rs1800532 is Associated with Suicide Attempt in
      Serbian Psychiatric Patients but does not Moderate the Effect of Recent Stressful
      Life Events.
AB  - Tryptophan hydroxylase 1 (TPH1) gene, coding for serotonin synthesizing enzyme,
      and recent stressful life events (SLEs) have been commonly associated with
      suicidal behavior. TPH1 has been also hypothesized to be involved in stress
      response mechanisms. The aim of this study was to assess TPH1 variant rs1800532
      and its possible interaction with recent SLEs as risk factors for suicide attempt
      (SA) in Serbian psychiatric patients, including 165 suicide attempters and 188
      suicide nonattempters. rs1800532 and recent SLEs were independently associated
      with SA, while rs1800532 did not moderate the effect of recent SLEs on SA
      vulnerability among Serbian psychiatric patients.

PMID- 27037950
TI  - Initiation of innate immune responses by surveillance of homeostasis
      perturbations.
AB  - Pathogen recognition, signaling transduction pathways, and effector mechanisms
      are necessary steps of innate immune responses that play key roles in the early
      phase of defense and in the stimulation of the later specific response of
      adaptive immunity. Here, we argue that in addition to the direct recognition of
      conserved common structural and functional molecular signatures of microorganisms
      using pattern recognition receptors, hosts can mount an immune response following
      the sensing of disruption in homeostasis as proximal reporters for infections.
      Surveillance of disruption of core cellular activities leading to defense
      responses is a flexible strategy that requires few additional components and that
      can effectively detect relevant threats. It is likely to be evolutionarily very
      conserved and ancient because it is operational in organisms that lack pattern
      recognition triggered immunity. A homeostasis disruption model of immune response
      initiation and modulation has broad implications for pathophysiology and
      treatment of disease and might constitute an often overlooked but central
      component of a comprehensive conceptual framework for innate immunity.

PMID- 27037952
TI  - Microvessels of the Heart.

PMID- 27037953
TI  - Corrigendum.

PMID- 27037951
TI  - Body mass index and risk of colorectal cancer according to tumor lymphocytic
      infiltrate.
AB  - Higher body mass index (BMI), higher body adiposity and obesity have been
      associated with increased risk of colorectal cancer. Evidence suggests that
      excess energy balance may influence systemic immune and inflammatory status.
      Thus, we hypothesized that the positive association between BMI and colorectal
      cancer risk might differ according to colorectal carcinoma subtypes according to
      levels of histopathological lymphocytic reaction to tumor. We collected biennial
      questionnaire data on weight and baseline height information in two prospective
      cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals
      Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional
      hazards regression models, we prospectively assessed the association between BMI
      and risk of colorectal cancer subtypes according to the degree of Crohn's-like
      lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular
      reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score,
      or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor
      tissue. Statistical significance level was adjusted for multiple hypotheses
      testing by Bonferroni correction. During follow up of 1,708,029 men and women
      (over 3,346,752 person-years), we documented 1,436 incident rectal and colon
      cancer cases with available formalin-fixed paraffin-embedded tumor tissue
      materials and pathological immunity data. BMI was significantly associated with
      higher risk of overall colorectal cancer (Ptrend  < 0.001); however, the
      association of BMI with colorectal carcinoma risk did not significantly differ by
      the level of lymphocytic reaction or T-cell infiltration in tumor tissue status
      (Pheterogeneity  > 0.10). BMI may be associated with risk of colorectal cancer
      regardless of levels of lymphocytic response to tumor.

PMID- 27037954
TI  - Mathematical modelling of angiogenesis using continuous cell-based models.
AB  - In this work, we develop a mathematical formalism based on a 3D in vitro model
      that is used to simulate the early stages of angiogenesis. The model treats cells
      as individual entities that are migrating as a result of chemotaxis and
      durotaxis. The phenotypes used here are endothelial cells that can be
      distinguished into stalk and tip (leading) cells. The model takes into account
      the dynamic interaction and interchange between both phenotypes. Next to the
      cells, the model takes into account several proteins such as vascular endothelial
      growth factor, delta-like ligand 4, urokinase plasminogen activator and matrix
      metalloproteinase, which are computed through the solution of a system of
      reaction-diffusion equations. The method used in the present study is classified
      into the hybrid approaches. The present study, implemented in three spatial
      dimensions, demonstrates the feasibility of the approach that is qualitatively
      confirmed by experimental results.

PMID- 27037955
TI  - Roles of ERalpha during mouse trophectoderm lineage differentiation: revealed by
      antagonist and agonist of ERalpha.
AB  - During mouse early embryogenesis, blastomeres increase in number by the morula
      stage. Among them, the outer cells are polarized and differentiated into
      trophectoderm (TE), while the inner cells remain unpolarized and give rise to
      inner cell mass (ICM). TE provides an important liquid environment for ICM
      development. In spite of extensive research, the molecular mechanisms underlying
      TE formation are still obscure. In order to investigate the roles of estrogen
      receptor alpha (ERalpha) in this course, mouse 8-cell embryos were collected and
      cultured in media containing ERalpha specific antagonist MPP and/or agonist PPT.
      The results indicated that MPP treatment inhibits blastocyst formation in a dose
      dependent manner, while PPT, at proper concentration, promotes the cavitation
      ratio of mouse embryos. Immunofluorescence staining results showed that MPP
      significantly decreased the nuclear expression of CDX2 in morula, but no
      significant changes of OCT4 were observed. Moreover, after MPP treatment, the
      expression levels of the genes related to TE specification, Tead4, Gata3 and
      Cdx2, were significantly reduced. Overall, these results indicated that ERalpha
      might affect mouse embryo cavitation by regulating TE lineage differentiation. 

PMID- 27037956
TI  - Cyclodextrins as Protective Agents of Protein Aggregation: An Overview.
AB  - Cyclodextrins are extensively used in different fields (e.g., catalysis,
      chromatography, pharma, supramolecular chemistry, bioorganic chemistry, and
      bioinorganic chemistry), and their applications have been widely reviewed. Their
      main application in the field of pharmaceutical is as a drug carrier. This review
      overviews, for the first time, the use of cyclodextrins and their derivatives as
      antiaggregant agents in a number of proteins (e.g., amyloid-beta, insulin,
      recombinant human growth hormone, prion protein, transthyretin, and alpha
      synuclein) and some multimeric enzymes. There are many diseases that are
      correlated to protein misfolding and amyloid formation processes affecting
      numerous organs and tissues. There are over 30 different amyloid proteins and a
      number of corresponding diseases. Alzheimer's disease is the most common
      neurodegenerative disease. Treatment of these diseases is still a goal to reach,
      and many molecules are studied in this perspective. Cyclodextrins have also been
      studied, and they show great potential; as such, further studies could be very
      promising. This review aims to be a stimulus for the design of new cyclodextrin
      derivatives to obtain multifunctional systems with antiaggregant activity. 

PMID- 27037957
TI  - An effector of apple proliferation phytoplasma targets TCP transcription factors
      a generalized virulence strategy of phytoplasma?
AB  - The plant pathogen Candidatus Phytoplasma mali (P. mali) is the causative agent
      of apple proliferation, a disease of increasing importance in apple-growing areas
      within Europe. Despite its economic importance, little is known about the
      molecular mechanisms of disease manifestation within apple trees. In this study,
      we identified two TCP (TEOSINTE BRANCHED/CYCLOIDEA/PROLIFERATING CELL FACTOR)
      transcription factors of Malus x domestica as binding partners of the P. mali
      SAP11-like effector ATP_00189. Phytohormone analyses revealed an effect of P.
      mali infection on jasmonates, salicylic acid and abscisic acid levels, showing
      that P. mali affects phytohormonal levels in apple trees, which is in line with
      the functions of the effector assumed from its binding to TCP transcription
      factors. To our knowledge, this is the first characterization of the molecular
      targets of a P. mali effector and thus provides the basis to better understand
      symptom development and disease progress during apple proliferation. As SAP11
      homologues are found in several Phytoplasma species infecting a broad range of
      different plants, SAP11-like proteins seem to be key players in phytoplasmal
      infection.

PMID- 27037958
TI  - Attitudes to legalizing cannabis use.
AB  - In this paper, we investigate the relationship between cannabis use and attitudes
      to legalizing the use of cannabis. Predictions from theory provide a means of
      learning about the roles of information, self interest and regret in explaining
      differences in attitudes to legalization between those who currently use, those
      who have used in the past and those who have never used. Our empirical
      investigation suggests that users have a greater awareness of cannabis not being
      as harmful as abstainers think it is. This may explain why individuals are more
      inclined to be in favor of legalizing cannabis once they have used it themselves.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037959
TI  - Effect of Liposome Size on Internal RNA Replication Coupled with Replicase
      Translation.
AB  - Cell membranes inhibit the diffusion of intracellular materials, and compartment
      size can strongly affect the intracellular biochemical reactions. To assess the
      effect of the size of microcompartments on intracellular reactions, we
      constructed a primitive cell model consisting of giant liposomes and a
      translation-coupled RNA replication (TcRR) system. The RNA was replicated by
      Qbeta replicase, which was translated from the RNA in giant liposomes
      encapsulating the cell-free translation system. A reporter RNA encoding the
      antisense strand of beta-glucuronidase was introduced into the system to yield a
      TcRR read-out (green fluorescence). We demonstrate that TcRR was hardly
      detectable in larger liposomes (230 fL) but was more effective in smaller (7.7
      fL) liposomes. Our experimental and theoretical results show that smaller
      microcompartments considerably enhance TcRR because the synthesized molecules,
      such as RNA and replicases, are more concentrated in smaller liposomes.

PMID- 27037960
TI  - The role of CHADS2 and CHA2 DS2 -VASc scores in the prediction of stroke in
      individuals without atrial fibrillation: a population-based study.
AB  - Essentials CHADS2 and CHA2 DS2 -VASc scores are used to predict stroke in atrial
      fibrillation (AF). These scores were calculated for a large cohort from the
      largest healthcare provider in Israel. The risk of stroke gradually increased
      with an increase in the scores in individuals without AF. Both scores have a
      relatively high performance for stroke prediction in individuals without AF.
      Click to hear Prof. Lowe's perspective on Arterial Thrombosis, Pathogenesis and
      Epidemiology SUMMARY: Background CHADS2 and CHA2 DS2 -VASc are validated scores
      used to predict stroke in patients with atrial fibrillation (AF). We aimed to
      examine the performance of these scores in predicting stroke in individuals
      without AF. Methods Using the computerized database of the largest HMO in Israel,
      we identified all not-anticoagulated adults, aged 50 years or older on 1 January
      2012. The cohort was followed for the occurrence of stroke or transient ischemic
      attack (TIA) until 31 December 2014. Results Of 1 053 871 individuals without AF
      at baseline, 34 215 developed stroke/TIA during a follow-up of 3 014 002 person
      years (stroke/TIA incidence rate, 1.14 per 100 person-years). The incidence rate
      of stroke/TIA increased in a graded manner with increasing CHADS2 score: 0.36,
      0.89, 1.89, 2.96, 4.31, 5.37 and 6.62 per 100 person-years for CHADS2 scores of 0
      to 6 points, respectively (P < 0.001). Results were similar for the CHA2 DS2 
      VASc score. A similar graded increasing trend in the stroke/TIA incidence rate
      was observed in a cohort of 46 657 patients with AF at baseline; however,
      stroke/TIA rates were higher in each score stratum compared with the rates of
      individuals without AF. The area under the receiver operating characteristic
      curve was 0.718 (95% CI, 0.715-0.721) and 0.714 (0.711-0.717) for CHADS2 and CHA2
      DS2 -VASc scores, respectively, in individuals without AF, and 0.606 (0.598
      0.614) and 0.610 (0.602-0.618), respectively, in individuals with AF. Conclusions
      CHADS2 and CHA2 DS2 -VASc scores have a relatively high performance for
      prediction of stroke/TIA in individuals without AF, which is comparable to their
      performance in patients with AF.

PMID- 27037961
TI  - A study of synthesis and properties of poly-3-hydroxybutyrate/diethylene glycol
      copolymers.
AB  - This study investigates synthesis of poly(3-hydroxybutyrate)/diethylene glycol
      copolymers (P3HB/DEG) by Cupriavidus eutrophus B-10646 cells as related to DEG
      concentration in the medium and the time when it is added to the culture of cells
      synthesizing P3HB. The study determines the limits of physiological effect of DEG
      on C. eutrophus cells, showing that at DEG concentrations above 30 g/L, it
      inhibits cell growth, decreasing cell concentration and total P3HB/DEG yield and
      inducing an increase in the degree of saturation of fatty acids in lipids of cell
      cytoplasmic membrane. A series of copolymers containing different molar fractions
      of DEG (between 0.13 and 3.0 mol%) have been synthesized and their
      physicochemical, physical/mechanical, and biological properties have been
      investigated as related to the chemical composition and proportions of DEG
      monomers of the polymers. (c) 2016 American Institute of Chemical Engineers
      Biotechnol. Prog., 32:1017-1028, 2016.

PMID- 27037962
TI  - Could erythrocyte omega-3 fatty acid levels be harbingers of bipolar disorder?

PMID- 27037963
TI  - Erratum.

PMID- 27037964
TI  - Confirmation of genetic testing results in haemostasis and thrombosis - survey of
      current practice in the field.

PMID- 27037965
TI  - Family-Based Therapy for Young Adults with Anorexia Nervosa Restores Weight.
AB  - OBJECTIVE: We examined the preliminary acceptability and efficacy of family-based
      therapy (FBT) for weight restoration in young adults (FBTY) with Anorexia Nervosa
      (AN). METHOD: Twenty-two primarily female participants ranging from age 18 to 26,
      with AN or atypical AN (ICD-10) and their support adults were enrolled in a 6
      month open trial of FBTY. Participants were assessed at baseline, after
      treatment, and at six and 12 month follow-up visits. The primary outcome was BMI
      and secondary outcomes included eating disorder psychopathology, current eating
      disorder obsessions, and compulsions, number of other Axis I disorders and global
      assessment of functioning. RESULTS: Although FBTY was rated as suitable by
      participants and their support adults, during FBTY, 9/22 participants dropped out
      and 3/22 dropped out at follow-up assessments. Despite being offered 18-20
      sessions over six months, a mean of 12 FBTY sessions (SD = 6) were attended.
      After FBTY, 15 of the intent-to-treat sample of 22 were no longer underweight
      (BMIs >= 19 kg/m(2) ) and 12 months after treatment, 13/22 were no longer
      underweight. The magnitude of the BMI increase during FBTY (Hedges g = 1.20, 95th
      percentile CI = 0.55-1.85) was comparable to findings for adolescent FBT for AN.
      Secondary outcomes also improved. DISCUSSION: FBTY for young adults with AN and
      atypical AN, which involves support adults participants have chosen, results in
      weight restoration that is sustained up to a year after treatment. (c) 2016 Wiley
      Periodicals, Inc. (Int J Eat Disord 2016; 49:701-707).

PMID- 27037966
TI  - A sensitive fluorescent nanosensor for chloramphenicol based on molecularly
      imprinted polymer-capped CdTe quantum dots.
AB  - A novel fluorescent nanosensor using molecularly imprinted silica nanospheres
      embedded CdTe quantum dots (CdTe@SiO2 @MIP) was developed for detection and
      quantification of chloramphenicol (CAP). The imprinted sensor was prepared by
      synthesis of molecularly imprinting polymer (MIP) on the hydrophilic CdTe quantum
      dots via reverse microemulsion method using small amounts of solvents. The
      resulting CdTe@SiO2 @MIP nanoparticles were characterized by fluorescence, UV-vis
      absorption and FT-IR spectroscopy and transmission electron microscopy. They
      preserved 48% of fluorescence quantum yield of the parent quantum dots. CAP
      remarkably quenched the fluorescence of prepared CdTe@SiO2 @MIP, probably via
      electron transfer mechanism. Under the optimal conditions, the relative
      fluorescence intensity of CdTe@SiO2 @MIP decreased with increasing CAP by a Stern
      Volmer type equation in the concentration range of 40-500 ug L(-1). The
      corresponding detection limit was 5.0 ug L(-1). The intra-day and inter-day
      values for the precision of the proposed method were all <4%. The developed
      sensor had a good selectivity and was applied to determine CAP in spiked human
      and bovine serum and milk samples with satisfactory results.

PMID- 27037967
TI  - Probing the interaction of caffeic acid with ZnO nanoparticles.
AB  - The binding of ZnO nanoparticles (NPs) and caffeic acid (CFA) was investigated
      using fluorescence quenching, UV/vis absorption spectrscopy, Fourier transform
      infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) and dynamic
      light scattering (DLS) at different temperatures. The study results indicated
      fluorescence quenching between ZnO NPs and CFA rationalized in terms of a static
      quenching mechanism or the formation of non-fluorescent CFA-ZnO. From
      fluorescence quenching spectral analysis, the binding constant (K(a)), number of
      binding sites (n) and thermodynamic properties were determined. Values of the
      quenching (K(SV)) and binding (K(a)) constants decrease with increasing
      temperature and the number of binding sites n = 2. The thermodynamic parameters
      determined using Van't Hoff equation indicated that binding occurs spontaneously
      involving the hydrogen bond, and van der Waal's forces played a major role in the
      reaction of ZnO NPs with CFA. The FTIR, TEM and DLS measurements also indicated
      differences in the structure, morphology and size of CFA, ZnO NPs and their
      corresponding CFA-ZnO.

PMID- 27037968
TI  - Fluorescence resonance energy transfer between bovine serum albumin and
      fluoresceinamine.
AB  - Physical binding-mediated organic dye direct-labelling of proteins could be a
      promising technology for bio-nanomedical applications. Upon binding, it was found
      that fluorescence resonance energy transfer (FRET) occurred between donor bovine
      serum albumin (BSA; an amphiphilic protein) and acceptor fluoresceinamine (FA; a
      hydrophobic fluorophore), which could explain fluorescence quenching found for
      BSA. FRET efficiency and the distance between FA and BSA tryptophan residues were
      determined to 17% and 2.29 nm, respectively. Using a spectroscopic
      superimposition method, the saturated number of FAs that bound to BSA was
      determined as eight to give a complex formula of FA8-BSA. Finally, molecular
      docking between BSA and FA was conducted, and conformational change that occurred
      in BSA upon binding to FA molecules was also studied by three-dimensional
      fluorescence microscopy.

PMID- 27037969
TI  - Changes in bacterial composition of biofilm in a metropolitan drinking water
      distribution system.
AB  - AIMS: This study examined the development of bacterial biofilms within a
      metropolitan distribution system. The distribution system is fed with different
      source water (i.e. groundwater, GW and surface water, SW) and undergoes different
      treatment processes in separate facilities. METHODS AND RESULTS: The biofilm
      community was characterized using 16S rRNA gene clone libraries and functional
      potential analysis, generated from total DNA extracted from coupons in biofilm
      annular reactors fed with onsite drinking water for up to 18 months. Differences
      in the bacterial community structure were observed between GW and SW.
      Representatives that explained the dissimilarity were associated with the classes
      Betaproteobacteria, Alphaproteobacteria, Actinobacteria, Gammaproteobacteria and
      Firmicutes. After 9 months the biofilm bacterial community from both GW and SW
      were dominated by Mycobacterium species. The distribution of the dominant
      operational taxonomic unit (OTU) (Mycobacterium) positively correlated with the
      drinking water distribution system (DWDS) temperature. CONCLUSIONS: In this
      study, the biofilm community structure observed between GW and SW were
      dissimilar, while communities from different locations receiving SW did not show
      significant differences. The results suggest that source water and/or the water
      quality shaped by their respective treatment processes may play an important role
      in shaping the bacterial communities in the distribution system. In addition,
      several bacterial groups were present in all samples, suggesting that they are an
      integral part of the core microbiota of this DWDS. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These results provide an ecological insight into biofilm bacterial
      structure in chlorine-treated drinking water influenced by different water
      sources and their respective treatment processes.

PMID- 27037970
TI  - Cytogenetic and immunohistochemical biomarker profiling of therapy-relevant
      factors in salivary gland carcinomas.
AB  - OBJECTIVES: There is currently no established algorithm for the molecular
      profiling of therapy-relevant defects in salivary gland carcinomas (SGC). HER2
      overexpression in a subfraction of SGC and low frequencies of EGFR mutations are
      known. Here, we established receptor and cell signalling profiles of 17 therapy
      relevant factors and propose a molecular diagnostic algorithm for SGC. MATERIALS
      AND METHODS: Formalin-fixed and paraffin-embedded tissue samples from SGC (n =
      38) were analysed with immunohistochemistry and fluorescence in situ
      hybridisation (FISH). RESULTS: Two or more expressed receptors and/or receptor
      gene amplification were detectable in eight of 38 (21%) tumours: HER2 3+/AR 1+,
      HER3 gene amplification/AR 1+/EGFR 1+, ER 3+/AR 1+, EGFR 2+/PR 1+ and EGFR 2+/PR
      1+/AR 1+. No FGFR1-3, MET, ALK1, ROS1, RET, BRAF nor VEGFA defects were
      detectable, and ERCC1 was not overexpressed. No PD1+ tumour-infiltrating T cells
      were detectable. CONCLUSION: Personalised therapy of patients with salivary gland
      carcinomas should include HER2 and EGFR signalling testing and, in negative
      cases, evaluation of rare potential target molecules. ERCC1 and PD1 do not appear
      to be reliable markers for the decision for or against chemotherapy or
      immunotherapy, respectively.

PMID- 27037971
TI  - Identifying children with autism spectrum disorder based on their face processing
      abnormality: A machine learning framework.
AB  - The atypical face scanning patterns in individuals with Autism Spectrum Disorder
      (ASD) has been repeatedly discovered by previous research. The present study
      examined whether their face scanning patterns could be potentially useful to
      identify children with ASD by adopting the machine learning algorithm for the
      classification purpose. Particularly, we applied the machine learning method to
      analyze an eye movement dataset from a face recognition task [Yi et al., 2016],
      to classify children with and without ASD. We evaluated the performance of our
      model in terms of its accuracy, sensitivity, and specificity of classifying ASD.
      Results indicated promising evidence for applying the machine learning algorithm
      based on the face scanning patterns to identify children with ASD, with a maximum
      classification accuracy of 88.51%. Nevertheless, our study is still preliminary
      with some constraints that may apply in the clinical practice. Future research
      should shed light on further valuation of our method and contribute to the
      development of a multitask and multimodel approach to aid the process of early
      detection and diagnosis of ASD. Autism Res 2016, 9: 888-898. (c) 2016
      International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27037972
TI  - Fiber/collagen composites for ligament tissue engineering: influence of elastic
      moduli of sparse aligned fibers on mesenchymal stem cells.
AB  - Electrospun microfibers are attractive for the engineering of oriented tissues
      because they present instructive topographic and mechanical cues to cells.
      However, high-density microfiber networks are too cell-impermeable for most
      tissue applications. Alternatively, the distribution of sparse microfibers within
      a three-dimensional hydrogel could present instructive cues to guide cell
      organization while not inhibiting cell behavior. In this study, thin (~5 fibers
      thick) layers of aligned microfibers (0.7 MUm) were embedded within collagen
      hydrogels containing mesenchymal stem cells (MSCs), cultured for up to 14 days,
      and assayed for expression of ligament markers and imaged for cell organization.
      These microfibers were generated through the electrospinning of polycaprolactone
      (PCL), poly(ester-urethane) (PEUR), or a 75/25 PEUR/PCL blend to produce
      microfiber networks with elastic moduli of 31, 15, and 5.6 MPa, respectively.
      MSCs in composites containing 5.6 MPa fibers exhibited increased expression of
      the ligament marker scleraxis and the contractile phenotype marker alpha-smooth
      muscle actin versus the stiffer fiber composites. Additionally, cells within the
      5.6 MPa microfiber composites were more oriented compared to cells within the 15
      and 31 MPa microfiber composites. Together, these data indicate that the
      mechanical properties of microfiber/collagen composites can be tuned for the
      engineering of ligament and other target tissues. (c) 2016 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 104A: 1894-1901, 2016.

PMID- 27037973
TI  - Intradetrusor injections of onabotulinum toxin A (Botox(r)) 300 U or 200 U versus
      abobotulinum toxin A (Dysport(r)) 750 U in the management of neurogenic detrusor
      overactivity: A case control study.
AB  - AIMS: To compare the outcomes of the first intradetrusor injections of
      abobotulinum toxin 750 U and onabotulinum toxin 200 and 300 U in patients with
      neurogenic detrusor overactivity (NDO). METHODS: A retrospective case-control
      study was conducted including 211 NDO patients treated in three consecutives eras
      with onabotulinum toxin 300 U (2004-2006; 80 patients), abobotulinum toxin 750 U
      (2007-2011; 78 patients) or onabotulinum toxin 200 U (2011-2014; 53 patients).
      Urodynamic and clinical parameters were compared between groups. The primary
      endpoint was the rates of success defined as the combination of urgency, urinary
      incontinence, and detrusor overactivity resolution. RESULTS: When comparing
      abobotulinum toxin to onabotulinum toxin any doses (200 or 300 U; n = 133),
      success rates were similar (65.4% vs. 55.6%; P = 0.16). Patients treated with
      abobotulinum toxin 750 U had higher success rate (65.4% vs. 41.5%; P = 0.007)
      compared to those who received onabotulinum toxin 200 U. In contrast, there were
      similar success rates in abobotulinum toxin 750 U and onabotulinum toxin 300 U
      groups (65.4% vs. 65%; P = 0.91) but with a trend towards longer interval between
      the first and the second injection in the onabotulinum toxin 300 U group (12.4
      vs. 9.3 months; P = 0.09). CONCLUSIONS: Intradetrusor injections of abobotulinum
      toxin 750 U for NDO provided better outcomes than injections of onabotulinum
      toxin 200 U. Success rates of abobotulinum toxin 750 U and onabotulinum toxin 300
      U were similar but interval between injections tended to be longer with
      onabotulinum toxin 300 U. Neurourol. Urodynam. 36:734-739, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27037974
TI  - Negative maple-leaf-like areas: a new clue for basal cell carcinoma margin
      recognition.

PMID- 27037975
TI  - Efficient Synthesis of Cyclic Block Copolymers by Rotaxane Protocol by
      Linear/Cyclic Topology Transformation.
AB  - High-yielding synthesis of cyclic block copolymer (CBC) using the rotaxane
      protocol by linear-cyclic polymer topology transformation was first demonstrated.
      Initial complexation of OH-terminated sec-ammonium salt and a crown ether was
      followed by the successive living ring-opening polymerizations of two lactones to
      a linear block copolymer having a rotaxane structure by the final capping of the
      propagation end. CBC was obtained in a high yield by an exploitation of the
      mechanical linkage through the translational movement of the rotaxane component
      to transform polymer structure from linear to cyclic. Furthermore, the change of
      the polymer topology was translated into a macroscopic change in crystallinity of
      the block copolymer. 

PMID- 27037976
TI  - Organelle redox autonomy during environmental stress.
AB  - Oxidative stress is generated in plants because of inequalities in the rate of
      reactive oxygen species (ROS) generation and scavenging. The subcellular redox
      state under various stress conditions was assessed using the redox reporter
      roGFP2 targeted to chloroplastic, mitochondrial, peroxisomal and cytosolic
      compartments. In parallel, the vitality of the plant was measured by ion leakage.
      Our results revealed that during certain physiological stress conditions the
      changes in roGFP2 oxidation are comparable to application of high concentrations
      of exogenous H2 O2 . Under each stress, particular organelles were affected.
      Conditions of extended dark stress, or application of elicitor, impacted chiefly
      on the status of peroxisomal redox state. In contrast, conditions of drought or
      high light altered the status of mitochondrial or chloroplast redox state,
      respectively. Amalgamation of the results from diverse environmental stresses
      shows cases of organelle autonomy as well as multi-organelle oxidative change.
      Importantly, organelle-specific oxidation under several stresses proceeded cell
      death as measured by ion leakage, suggesting early roGFP oxidation as predictive
      of cell death. The measurement of redox state in multiple compartments enables
      one to look at redox state connectivity between organelles in relation to
      oxidative stress as well as assign a redox fingerprint to various types of stress
      conditions.

PMID- 27037977
TI  - Follow-up with primary care providers for elevated glycated haemoglobin
      identified at the dental visit.
AB  - OBJECTIVES: This study examined patient experiences after receiving elevated
      diabetes screening values using blood collected at a dental clinic. It explores
      patients' reactions to screening, whether or not they sought recommended medical
      follow-up, and facilitating factors and barriers to obtaining follow-up care.
      METHODS: At the comprehensive care clinics at a large, urban College of Dentistry
      in the United States, haemoglobin A1C (HbA1C) values were obtained from 379 study
      participants who had not been previously diagnosed with diabetes. In all, 169
      (44.6%) had elevated HbA1C values. We analysed quantitative and qualitative data
      concerning these patients' follow-up with primary care providers (PCPs). RESULTS:
      We were able to contact 112 (66.3%) of the 169 study participants who had an
      elevated HbA1C reading. Of that group, 61 (54.5%) received recommended follow-up
      care from a PCP within 3 months, and an additional 28 (25.0%) said they intended
      to seek such care. Qualitative themes included the following: the screening
      letter - opportunity or burden, appreciation for the 3-month follow-up call and
      barriers to medical follow-up that included the following: lack of knowledge
      about diabetes, not understanding the importance of follow-up, busyness,
      financial concerns, fear and denial. CONCLUSIONS: Quantitative and qualitative
      data demonstrate that dentists, dental hygienists and nurses are well poised to
      discover and translate new models of patient-centred, comprehensive care to
      patients with oral and systemic illness.

PMID- 27037978
TI  - Selective separation and characterisation of stress degradation products and
      process impurities of prucalopride succinate by LC-QTOF-MS/MS.
AB  - The present study reports the degradation behaviour of a new prokinetic agent,
      Prucalopride succinate, under various stress conditions as per International
      Conference on Harmonization guidelines (ICH, Q1A (R2)). The investigation
      involved monitoring decomposition of the drug under hydrolytic (acidic, basic and
      neutral), oxidative, photolytic and thermal stress conditions followed by
      characterization of the degradation products (DPs) and process related impurities
      (IMPs). A rapid, precise, accurate and robust reverse phase high performance
      liquid chromatography (RP-HPLC) method has been developed involving mobile phase
      of 20mM ammonium bicarbonate buffer and acetonitrile: methanol (80:20v/v) on a
      Waters Xbridge-C8 (150mm*4.6mm i.d., 3.5MUm) column using gradient elution. The
      drug was found to be degraded in hydrolytic (acidic) and oxidative conditions,
      whereas it was stable under basic and neutral hydrolytic, photolytic and thermal
      stress conditions. The method was extended to LC-ESI-QTOF-MS/MS for the
      structural characterization of DPs and process related IMPs. Structural
      characterization was carried out based on the generated molecular formula of DPs
      and its fragment ions. It has been observed that two major DPs were formed under
      each acid hydrolysis and oxidative stress conditions. The most probable
      mechanisms involved in the formation of DPs were also proposed. Finally, the
      method was validated in the term of specificity, linearity, accuracy, precision,
      and robustness as per ICH guidelines, Q2 (R1). 

PMID- 27037979
TI  - Development of a UFLC-MS/MS method for the simultaneous determination of seven
      tea catechins in rat plasma and its application to a pharmacokinetic study after
      administration of green tea extract.
AB  - A rapid, sensitive and selective ultra-fast liquid chromatography-tandem mass
      spectrometry (UFLC-MS/MS) method was developed and validated for simultaneous
      determination of seven green tea catechins including catechin (C), (-)
      epicatechin (EC), gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-epicatechin
      3-gallate (ECG), gallocatechin-3-gallate (GCG) and (-)-epigallocatechin-3-gallate
      (EGCG) in rat plasma. The plasma samples were firstly hydrolysed with the mixture
      of beta-glucuronidase and sulfatase, which were then extracted by liquid-liquid
      extraction with ethyl acetate-isopropanol (1:1, v/v). The analytes were separated
      on a Venusil MP C18 column (Venusil, China) with a gradient elution at a flow
      rate of 0.4mL/min. The detection was performed in negative ionization and
      multiple reaction monitoring (MRM) mode. All the calibration curves exhibited
      good linearity (r>0.9943) with intra- and inter-day precisions of less than 14.3%
      and the accuracy deviations ranging from -8.8% to 7.5%. The extraction recoveries
      of the analytes and ethyl gallate (internal standard) were all more than 72%. The
      validated method was successfully applied to a pharmacokinetic study of seven
      catechins in rat plasma after oral administration of the green tea extract at
      different doses of 0.4, 1.2 and 2.0g/kg. 

PMID- 27037980
TI  - Validated liquid chromatography-tandem mass spectrometry method for simultaneous
      determination of clopamide, reserpine and dihydroergotoxine: Application to
      pharmacokinetics in human plasma.
AB  - A simple, sensitive and rapid high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) method was developed and validated for the simultaneous
      quantitation of clopamide, reserpine and dihydroergotoxine (ergoloid mesylates)
      in human plasma. Under basic conditions, liquid-liquid extraction using ethyl
      acetate was efficiently used for extraction of the analytes from plasma samples
      in presence of indapamide as internal standard (IS). The analytes were separated
      with isocratic elution on Phenomenex((r)) Synergi Fusion-RP 80A column (50*4.6mm,
      4MUm). With positive ion electrospray ionization (ESI), the analytes were
      quantified and monitored on a triple quadrupole mass spectrometer using Multiple
      Reaction Monitoring (MRM) scanning mode. Satisfactory results regarding
      linearity, recovery, stability, accuracy and precision of the analytes were
      obtained. The method was linear in the concentration range of 0.04-30.00ng/mL for
      reserpine, 1-96.00ng/mL for clopamide, and 0.05-40.00ng/mL for dihydroergotoxine
      alkaloids, respectively. For all analytes, the high sensitivity of HPLC-MS/MS
      method revealed sufficient lower limit of quantification (LLOQ) ranged from 0.04
      1ng/mL using 1mL of plasma. The recoveries from spiked control samples were
      >=86.16% for all analytes and IS. The intra- and inter-day precision variations
      were lower than 13.03% while the accuracy values ranged from 91.76% to 111.50%.
      The developed method was successfully applied to pharmacokinetic study of fixed
      dose combination of clopamide, reserpine and dihydroergotoxine in healthy male
      volunteers. 

PMID- 27037981
TI  - A randomised cross-over comparison of the transverse and longitudinal techniques
      for ultrasound-guided identification of the cricothyroid membrane in morbidly
      obese subjects.
AB  - We compared the transverse and longitudinal approaches to ultrasound-guided
      identification of the cricothyroid membrane, to determine which was faster and
      more successful. Forty-two anaesthetists received a one-hour structured training
      programme consisting of e-learning, a lecture and hands-on training, and then
      applied both techniques in a randomised, cross-over sequence to obese females
      with body mass index 39.0 - 43.9 kg.m(-2) . The mean (SD) time to identify the
      cricothyroid membrane was 24.0 (12.4) s using the transverse technique compared
      with 37.6 (17.9) s for the longitudinal technique (p = 0.0003). Successful
      identification of the cricothyroid membrane was achieved by 38 (90%)
      anaesthetists using either technique. All anaesthetists were successful in
      identifying the cricothyroid membrane with at least one of the techniques. We
      advocate the learning and application of these two techniques for identification
      of the cricothyroid membrane before starting anaesthesia in difficult patients,
      especially when anatomical landmarks are impalpable. Further use in emergency
      situations is feasible, if clinicians have experience and the ultrasound machine
      is readily available.

PMID- 27037982
TI  - Recommendations for the Evaluation of Left Ventricular Diastolic Function by
      Echocardiography: An Update from the American Society of Echocardiography and the
      European Association of Cardiovascular Imaging.

PMID- 27037983
TI  - Infective Endocarditis: A Deadly Disease if Diagnosed Too Late.

PMID- 27037984
TI  - Shifting the Spotlight onto the Forgotten Ventricle: Role of the Right Ventricle
      in Low-Flow, Low-Gradient Aortic Stenosis.

PMID- 27037985
TI  - The Point of Care.

PMID- 27037986
TI  - From Mentee to Mentor: A Cardiovascular Sonographer's Perspective.

PMID- 27037987
TI  - Procedural TEE: Sometimes Hard to Swallow.

PMID- 27037988
TI  - Encouraging overweight students with intellectual disability to actively perform
      walking activity using an air mouse combined with preferred stimulation.
AB  - This study continues the research on using an air mouse as a physical activity
      detector. An air mouse is embedded with a MEMS (Micro Electro Mechanical Systems)
      gyro sensor, which can measure even the slightest movement in the air. The air
      mouse was strapped to one of each participant's calves to detect walking
      activity. This study was conducted to evaluate whether four students with
      intellectual disability who were overweight and disliked exercising could be
      motivated to engage in walking actively by linking the target response with
      preferred stimulation. Single-subject research with ABAB design was adopted in
      this study. The experimental data showed substantial increases in the
      participants' target responses (i.e. the performance of the activity of walking)
      during the intervention phases compared to the baseline phases. The practical and
      developmental implications of the findings are discussed. 

PMID- 27037989
TI  - Subjective happiness among mothers of children with disabilities: The role of
      stress, attachment, guilt and social support.
AB  - BACKGROUND: Parenting a child with disabilities might affect the happiness of the
      mothers. Hence we adapted Wallander, Varni, Babani, Banis, and Wilcox's (1989)
      disability-stress-coping model to examine the impact of risk factors (specific
      stressors related to the child's disability) on the mother's adaptation
      (happiness). Intrapersonal factors (attachment) and social-ecological factors
      (social support) were hypothesized to predict adaptation. Both constitute 'risk
      resistant' factors, which are mediated by the mother's perceived general stress
      and guilt. METHOD: 191 mothers of a child with a developmental disability (ages 3
      7) answered questionnaires on happiness, specific and general stress, attachment,
      guilt and social support. RESULTS: Attachment avoidance was directly and
      negatively associated with mothers' happiness. General stress was negatively
      associated with happiness, and mediated the association between anxious
      attachment, support, and specific stress with happiness. Guilt was negatively
      associated with happiness, and served as a mediator between attachment anxiety
      and support and happiness. CONCLUSION: The findings of the current research show
      direct and indirect associations of risk factors with happiness and the role of
      general stress and feelings of guilt as mediators. IMPLICATIONS: This study
      stresses the importance of attachment and social support to happiness and sheds
      light on the unique role of guilt in promoting or inhibiting happiness.

PMID- 27037990
TI  - Corrigendum: Oxychlorination-Dehydrochlorination Chemistry on Bifunctional Ceria
      Catalysts for Intensified Vinyl Chloride Production.

PMID- 27037991
TI  - Corrigendum: Anion Recognition in Water: Recent Advances from a Supramolecular
      and Macromolecular Perspective.

PMID- 27037993
TI  - Asymmetric Synthesis of Axinellamines A and B.
AB  - Axinellamines A and B are broad-spectrum antibacterial pyrrole-imidazole
      alkaloids that have a complex polycyclic skeleton. A new asymmetric synthesis of
      these marine sponge metabolites is described herein, featuring an oxidative
      rearrangement and an anchimeric chlorination reaction. 

PMID- 27037994
TI  - Direct Electrophilic (Benzenesulfonyl)Difluoromethylthiolation with a Shelf
      Stable Reagent.
AB  - The (benzenesulfonyl)difluoromethylsulfanyl (PhSO2CF2S) group is a valuable
      substituent with specific properties which can provide access to new applications
      of fluoroalkylthiolated compounds. Direct introduction of this moiety can be
      performed by in an electrophilic manner by using a new shelf-stable reagent,
      namely a (benzenesulfonyl)difluoromethanesulfenamide. Furthermore, mild magnesium
      mediated reduction of the PhSO2CF2S group leads to a facile synthesis of
      difluoromethylthiolated molecules and their deuterated analogs.

PMID- 27037995
TI  - Identification of non-random sequence properties in groups of signature peptides
      obtained in random sequence peptide microarray experiments.
AB  - Immunosignaturing is an emerging experimental technique that uses random sequence
      peptide microarrays to detect antibodies produced by the immune system in
      response to a particular disease. Two important questions regarding
      immunosignaturing are "Do microarray peptides that exhibit a strong affinity to a
      given type of antibodies share common sequence properties?" and "If so, what are
      those properties?" In this work, three statistical tests designed to detect non
      random patterns in the amino acid makeup of a group of microarray peptides are
      presented. One test detects patterns of significantly biased amino acid usage,
      whereas the other two detect patterns of significant bias in the biochemical
      properties. These tests do not require a large number of peptides per group. The
      tests were applied to analyze 19 groups of peptides identified in
      immunosignaturing experiments as being specific for antibodies produced in
      response to various types of cancer and other diseases. The positional
      distribution of the biochemical properties of the amino acids in these 19 peptide
      groups was also studied. Remarkably, despite the random nature of the sequence
      libraries used to design the microarrays, a unique group-specific non-random
      pattern was identified in the majority of the peptide groups studied. (c) 2016
      Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 318-329, 2016. 

PMID- 27037996
TI  - Dietary nitrate enhances arterial oxygen saturation after dynamic apnea.
AB  - Breath-hold divers train to minimize their oxygen consumption to improve their
      apneic performance. Dietary nitrate has been shown to reduce the oxygen cost in a
      variety of situations, and our aim was to study its effect on arterial oxygen
      saturation (SaO2 ) after dynamic apnea (DYN) performance. Fourteen healthy male
      apnea divers (aged 33 +/- 11 years) received either 70 mL of concentrated nitrate
      rich beetroot juice (BR) or placebo (PL) on different days. At 2.5 h after
      ingesting the juice, they were asked to perform 2 * 75 m DYN dives in a pool with
      4.5-min recovery between dives. Each dive started after 2-min countdown and
      without any warm-up apneas, hyperventilation, or lung packing. SaO2 and heart
      rate were measured via pulse oximetry for 90 s before and after each dive. Mean
      SaO2 nadir values after the dives were 83.4 +/- 10.8% with BR and 78.3 +/- 11.0%
      with PL (P < 0.05). At 20-s post-dive, mean SaO2 was 86.3 +/- 10.6% with BR and
      79.4 +/- 10.2% with PL (P < 0.05). In conclusion, BR juice was found to elevate
      SaO2 after 75-m DYN. These results suggest an oxygen conserving effect of dietary
      nitrate supplementation, which likely has a positive effect on maximal apnea
      performance.

PMID- 27037997
TI  - Collaborative Divorce: An Effort to Reduce the Damage of Divorce.
AB  - Divorce has been trapped in the adversarial system of the courts, a system ill
      suited to the needs of a family attempting to reorganize itself and still
      safeguard the well-being of its members. Collaborative divorce (CD) is a
      relatively new approach comprising an interdisciplinary professional team trained
      to help the divorcing family arrive at a financial, legal, and emotional
      settlement. The CD approach is designed to assist both members of the couple and
      their children transition into a more constructive future wherein they can still
      be a family. The structure and adversarial approach of the courts have been
      replaced by collaborative structures and principles developed to encourage
      honesty and cooperation. The case presented illustrates how this actually works. 

PMID- 27037998
TI  - Pancreatic volume is reduced in patients with latent autoimmune diabetes in
      adults.
AB  - AIMS: This study aimed to compare pancreatic volume and its clinical significance
      among patients with type 2 diabetes mellitus (DM), adult-onset type 1 DM and
      latent autoimmune diabetes in adults (LADA). METHODS: This is a cross-sectional
      study. One hundred twenty-six outpatients (68 with LADA and 58 with type 1 DM)
      and 158 inpatients (71 with type 2 DM and 87 non-diabetic controls) were
      recruited during May-July 2013 in Shanghai Jiao Tong University Affiliated Sixth
      People's Hospital. All the patients underwent abdominal computerized tomography;
      pancreatic volume was then calculated. RESULTS: The mean pancreatic volume was
      highest in the controls, followed by those in patients with type 2 DM, LADA and
      type 1 DM. The pancreatic volume in LADA was comparable with that in type 2 DM
      but significantly greater than that in type 1 DM (p < 0.05). The pancreatic
      volume in patients with LADA was significantly correlated with sex, waist
      circumference, body surface area, body mass index, diastolic blood pressure and
      high-density lipoprotein cholesterol (all p < 0.05). The correlation between
      pancreatic volume and fasting C-peptide was high in patients with LADA (r =
      0.643, p < 0.001) and moderate in patients with type 2 DM (r = 0.467, p < 0.001).
      The area under the receiver operating characteristic curve for pancreatic volume
      predictive of absolute insulin deficiency (FCP < 0.9 ng/mL) was 0.85 (0.76-0.94)
      in LADA. CONCLUSIONS: Pancreatic atrophy in LADA was less marked than in type 1
      DM. Pancreatic atrophy may suggest reduced level of fasting C-peptide in patients
      with LADA. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27037999
TI  - Consumer acceptance of patient-performed mobile teledermoscopy for the early
      detection of melanoma.
AB  - BACKGROUND: Mobile teledermoscopy allows consumers to send images of skin lesions
      to a teledermatologist for remote diagnosis. Currently, technology acceptance of
      mobile teledermoscopy by people at high risk of melanoma is unknown. OBJECTIVES:
      We aimed to determine the acceptance of mobile teledermoscopy by consumers based
      on perceived usefulness, ease of use, compatibility, attitude/intention,
      subjective norms, facilitators and trust before use. Consumer satisfaction was
      explored after use. METHODS: Consumers aged 50-64 years at high risk of melanoma
      (fair skin or previous skin cancer) were recruited from a population-based cohort
      study and via media announcements in Brisbane, Australia in 2013. The
      participants completed a 27-item questionnaire preteledermoscopy modified from a
      technology acceptance model. The first 49 participants with a suitable smartphone
      then conducted mobile teledermoscopy in their homes for early detection of
      melanoma and were asked to rate their satisfaction. RESULTS: The
      preteledermoscopy questionnaire was completed by 228 participants. Most
      participants (87%) agreed that mobile teledermoscopy would improve their skin
      self-examination performance and 91% agreed that it would be in their best
      interest to use mobile teledermoscopy. However, nearly half of participants (45%)
      were unsure about whether they had complete trust in the telediagnosis. The
      participants who conducted mobile teledermoscopy (n = 49) reported that the
      dermatoscope was easy to use (94%) and motivated them to examine their skin more
      often (86%). However, 18% could not take photographs in hard-to-see areas and 35%
      required help to submit the photograph to the teledermatologist. CONCLUSIONS:
      Mobile teledermoscopy consumer acceptance appears to be favourable. This new
      technology warrants further assessment for its utility in the early detection of
      melanoma or follow-up.

PMID- 27038000
TI  - Tumour stroma-derived lipocalin-2 promotes breast cancer metastasis.
AB  - Tumour cell-secreted factors skew infiltrating immune cells towards a tumour
      supporting phenotype, expressing pro-tumourigenic mediators. However, the
      influence of lipocalin-2 (Lcn2) on the metastatic cascade in the tumour micro
      environment is still not clearly defined. Here, we explored the role of stroma
      derived, especially macrophage-released, Lcn2 in breast cancer progression.
      Knockdown studies and neutralizing antibody approaches showed that Lcn2
      contributes to the early events of metastasis in vitro. The release of Lcn2 from
      macrophages induced an epithelial-mesenchymal transition programme in MCF-7
      breast cancer cells and enhanced local migration as well as invasion into the
      extracellular matrix, using a three-dimensioanl (3D) spheroid model. Moreover, a
      global Lcn2 deficiency attenuated breast cancer metastasis in both the MMTV-PyMT
      breast cancer model and a xenograft model inoculating MCF-7 cells pretreated with
      supernatants from wild-type and Lcn2-knockdown macrophages. To dissect the role
      of stroma-derived Lcn2, we employed an orthotopic mammary tumour mouse model.
      Implantation of wild-type PyMT tumour cells into Lcn2-deficient mice left primary
      mammary tumour formation unaltered, but specifically reduced tumour cell
      dissemination into the lung. We conclude that stroma-secreted Lcn2 promotes
      metastasis in vitro and in vivo, thereby contributing to tumour progression. Our
      study highlights the tumourigenic potential of stroma-released Lcn2 and suggests
      Lcn2 as a putative therapeutic target. Copyright (c) 2016 Pathological Society of
      Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 27038001
TI  - Pharmacodynamics, pharmacokinetics, and safety of ticagrelor in Chinese patients
      with stable coronary artery disease.
AB  - AIM: The aim of the study was to assess ticagrelor's effects on inhibition of
      platelet aggregation (IPA), P2Y12 reaction units (PRU, measure of platelet P2Y12
      receptor blockade), pharmacokinetic (PK) parameters and safety in Chinese
      patients with stable coronary artery disease (CAD). METHODS: This was an open
      label, single centre, randomized study. Thirty-six patients on low dose aspirin
      (75-100 mg day(-1) ) received ticagrelor 45, 60 or 90 mg (single dose, days 1 and
      7; twice daily, days 3-6). IPA (final extent), PRU and ticagrelor and AR
      C124910XX plasma concentrations were determined. RESULTS: On day 1, peak IPA >80%
      occurred 2-6 h post-dose (all doses). PRU was markedly reduced at 1 h vs.
      baseline (all doses). With ticagrelor 45 and 90 mg twice daily, maximum IPA
      (mean, SD) was 91% (13%), and 99% (3%), and maximum PRU reduction from baseline
      (mean, SD) was 82% (17%) and 92% (9%), respectively. Approximate dose
      proportional increases (mean [%CV]; 45 vs. 90 mg twice daily) in ticagrelor Cmax
      (616 [37] vs. 1273 [43] ng ml(-1) ) and AUC (3882 [42] vs. 8206 [51] ng ml(-1) h)
      and AR-C124910XX parameters were seen. Pharmacodynamic and PK differences between
      45 and 60 mg were small. No safety issues were identified. CONCLUSIONS: In
      Chinese patients with CAD, ticagrelor (45, 60 and 90 mg) markedly reduced
      platelet aggregation. The IPA and PRU magnitude increased generally with
      increasing doses. However, the mean pharmacodynamic differences between 45 and 60
      mg doses were small. Following single and multiple doses, the mean Cmax and AUC
      values of ticagrelor and AR-C124910XX increased approximately dose proportionally
      between 45 and 90 mg doses.

PMID- 27038002
TI  - Molecular phylogeny of Zeacarpa (Ralfsiales, Phaeophyceae) proposing a new family
      Zeacarpaceae and its transfer to Nemodermatales.
AB  - Zeacarpa leiomorpha is a crustose brown alga endemic to South Africa. The species
      has been tentatively placed in Ralfsiaceae, but its ordinal assignment has been
      uncertain. The molecular phylogeny of brown algae based on concatenated DNA
      sequences of seven chloroplast and mitochondrial gene sequences (atpB, psaA,
      psaB, psbA, psbC, rbcL, and cox1) of taxa covering most of the orders revealed
      the most related phylogenetic relationship of Z. leiomorpha to Nemoderma
      tingitanum (Nemodermatales) rather than Ralfsiaceae (Ralfsiales).
      Morphologically, Zeacarpa and Nemoderma share crustose thallus structure and
      multiple discoidal chloroplasts without pyrenoids in each cell, however, the
      formation of lateral unilocular zoidangia in tufts in loose upright filaments in
      Zeacarpa is distinctive in brown algae. Considering the relatively distant
      genetic divergence between the two taxa, comparable to that among families or
      orders in representative brown algae, in addition to the above-mentioned unique
      morphological features, we propose the classification of Zeacarpa in a new family
      Zeacarpaceae in the order Nemodermatales.

PMID- 27038003
TI  - Signal or noise: brain network interactions underlying the experience and
      training of mindfulness.
AB  - A broad set of brain regions has been associated with the experience and training
      of mindfulness. Many of these regions lie within key intrinsic brain networks,
      including the executive control, salience, and default networks. In this paper,
      we review the existing literature on the cognitive neuroscience of mindfulness
      through the lens of network science. We describe the characteristics of the
      intrinsic brain networks implicated in mindfulness and summarize the relevant
      findings pertaining to changes in functional connectivity (FC) within and between
      these networks. Convergence across these findings suggests that mindfulness may
      be associated with increased FC between two regions within the default network:
      the posterior cingulate cortex and the ventromedial prefrontal cortex.
      Additionally, extensive meditation experience may be associated with increased FC
      between the insula and the dorsolateral prefrontal cortex. However, little
      consensus has emerged within the existing literature owing to the diversity of
      operational definitions of mindfulness, neuroimaging methods, and network
      characterizations. We describe several challenges to develop a coherent cognitive
      neuroscience of mindfulness and to provide detailed recommendations for future
      research.

PMID- 27038004
TI  - Iridium-Catalyzed Diastereoselective and Enantioselective Allylic Substitutions
      with Acyclic alpha-Alkoxy Ketones.
AB  - The asymmetric alkylation of acyclic ketones is a longstanding challenge in
      organic synthesis. Reported herein are diastereoselective and enantioselective
      allylic substitutions with acyclic alpha-alkoxy ketones catalyzed by a
      metallacyclic iridium complex to form products with contiguous stereogenic
      centers derived from the nucleophile and electrophile. These reactions occur
      between allyl methyl carbonates and unstabilized copper(I) enolates generated in
      situ from acyclic alpha-alkoxy ketones. The resulting products can be readily
      converted into enantioenriched tertiary alcohols and tetrahydrofuran derivatives
      without erosion of enantiomeric purity.

PMID- 27038005
TI  - Exploring thermography: a promising tool in differentiation between infection and
      ischemia of the acra in systemic sclerosis.

PMID- 27038006
TI  - Modification of impulse generation during pique turns with increased rotational
      demands.
AB  - During initiation of a pique turn, a dancer generates impulse to achieve the
      desired lateral translation and whole-body rotation. The goal of this study was
      to determine how individuals regulate impulse generation when initiating pique
      turns with increased rotational demands. Skilled dancers (n=10) performed single
      (~360 degrees ) and double (~720 degrees ) pique turns from a stationary
      position. Linear and angular impulse generated by the push and turn legs were
      quantified using ground reaction forces and compared across turn conditions as a
      group and within a dancer using probability-based statistical methods. The
      results indicate that as the rotation demands of the pique turn increased, the
      net angular impulse generated increased whereas net lateral impulse decreased.
      Early during turn initiation, the free moment contributed to angular impulse
      generation. Later during turn initiation, horizontal reaction forces were
      controlled to generate angular impulse. As rotational demands increased, the
      moment applied increased primarily from redirection of the horizontal reaction
      force (RFh) at the push leg and a combination of RFh magnitude and moment arm
      increases at the turn leg. RFh at each leg were coordinated to limit unwanted net
      linear impulse. Knowledge of observed subject-specific mechanisms is important to
      inform the design of turning performance training tools. 

PMID- 27038007
TI  - High plasma osteocalcin is associated with low blood haemoglobin in elderly men:
      the MrOS Sweden Study.
AB  - BACKGROUND: It has been suggested that osteoblasts are involved in the regulation
      of haematopoietic stem cells. Whether osteocalcin, which is derived from
      osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels
      is not known. OBJECTIVE: To determine whether plasma osteocalcin is a determinant
      of Hb in elderly men. METHODS: A total of 993 men (mean age 75.3 +/- 3.2 years)
      participated in the population-based MrOS (osteoporotic fractures in men) study.
      Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments
      were made for potential confounders (i.e. age, body mass index, erythropoietin,
      total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C).
      RESULTS: Hb correlated (age adjusted) negatively with osteocalcin in the total
      study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men
      (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was
      more likely that Hb would be in the lowest quartile (odds ratio per SD decrease
      in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were
      negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men
      (47/812) (Hb <130 g L(-1) ) had significantly higher mean osteocalcin levels than
      nonanaemic men (33.9 vs. 27.1 MUg L(-1) , P < 0.001). In multiple stepwise linear
      regression analyses (adjusted for age, body mass index, total oestradiol,
      adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and
      holotranscobalamin), osteocalcin was an independent predictor of Hb concentration
      in nondiabetic men (P < 0.05). CONCLUSIONS: These data add further support to the
      evidence indicating that the bone-specific protein osteocalcin has several
      endocrine functions targeting the pancreas, testes, adipocytes, brain. An
      additional novel finding is that osteocalcin may also have a paracrine function
      as a regulator of haematopoiesis.

PMID- 27038008
TI  - Asymmetry in functional connectivity of the human habenula revealed by high
      resolution cardiac-gated resting state imaging.
AB  - The habenula is a hub for cognitive and emotional signals that are relayed to the
      aminergic centers in the midbrain and, thus, plays an important role in goal
      oriented behaviors. Although it is well described in rodents and non-human
      primates, the habenula functional network remains relatively uncharacterized in
      humans, partly because of the methodological challenges associated with the
      functional magnetic resonance imaging of small structures in the brain. Using
      high-resolution cardiac-gated resting state imaging in healthy humans and
      precisely identifying each participants' habenula, we show that the habenula is
      functionally coupled with the insula, parahippocampus, thalamus, periaqueductal
      grey, pons, striatum and substantia nigra/ventral tegmental area complex.
      Furthermore, by separately examining and comparing the functional maps from the
      left and right habenula, we provide the first evidence of an asymmetry in the
      functional connectivity of the habenula in humans. Hum Brain Mapp 37:2602-2615,
      2016. (c) 2016 The Authors Human Brain Mapping Published by Wiley Periodicals,
      Inc.

PMID- 27038009
TI  - Association between human papillomavirus type 16 E6 and E7 variants with
      subsequent persistent infection and recurrence of cervical high-grade squamous
      intraepithelial lesion after conization.
AB  - The study aimed to detect the variants of human papillomavirus (HPV) type 16 E6
      and E7 in patients with cervical high-grade squamous intraepithelial lesion
      (HSIL), and to determine the existence and recurrence of persistent infection
      after treatment with loop electrosurgical excision procedure (LEEP).
      Preoperatively collected cervical exfoliated cells from 100 HPV 16 positive HSIL
      patients enrolled in the study were used to test for E6 and E7 variants. Follow
      ups which included TCT, HPV test, and colposcopy were performed every 3 months
      after the operation, and colposcopic biopsy and endocervical curettage were
      performed for patients with abnormalities. Patients were followed for 2 years,
      and recurrence was defined as detecting low-grade squamous intraepithelial lesion
      (LSIL) or relapse of HSIL in 1 year. In 81% of patients, the E6 variant was the
      Asian prototype (As.P), 14% of patients had the European variant, 2% had the
      European prototype (EP), and 3% had the African 1 variant (Af1). The HPV16 could
      be easily cleared by LEEP in patients with As.P. Persistent infection or
      recurrence was very rare in this group. The patients with European variants T350G
      or A442C had a significantly higher incidence of persistent and recurring HPV16
      infection. In conclusion, (i) in most cases, As.P caused HSIL. (ii) The European
      variant E6 T350G/A442C may be associated with higher rates of recurring and
      persistent HPV16 infection after the LEEP. (iii) The E7 gene mutation may not be
      a risk factor for recurring HSIL caused by HPV16 or persistent infection. J. Med.
      Virol. 88:1982-1988, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038010
TI  - Umbilical Cord Serum 25-Hydroxyvitamin D Concentrations and Relation to
      Birthweight, Head Circumference and Infant Length at Age 14 Days.
AB  - BACKGROUND: Insufficient supply of vitamin D during early development may
      negatively affect offspring growth. METHODS: We examined the association between
      umbilical cord (UC) serum 25-hydroxyvitamin D (25(OH)D) concentrations and infant
      size in a study of two Faroese birth cohorts of 1038 singleton infants. In the
      third trimester, the pregnant women completed questionnaires, and clinical
      examination included birthweight, head circumference, and infant length at age 14
      days. RESULTS: Fifty-three percent of the newborn population had UC 25(OH)D < 25
      nmol/L as determined by LC-MS/MS. Using multiple linear regression models with
      adjustment for pre-pregnancy BMI, sex, parity, gestational age, or infant age at
      examination, season of birth, smoking, gestational diabetes, examiner, and cohort
      identity, we found no relationship between birthweight or head circumference and
      UC 25(OH)D. However, infants with vitamin D status <12 nmol/L had a 0.49 (95%
      confidence interval 0.05, 0.93) cm lower length than infants with vitamin D
      status >50 nmol/L in models further adjusted for birthweight. CONCLUSION: Our
      data suggest that umbilical cord serum 25(OH)D concentrations are positively
      associated with infant length but not with birthweight and head circumference.
      Although the paediatric relevance of the observed association is unclear, the
      possible long-term consequences of late-pregnancy hypovitaminosis D deserve
      attention.

PMID- 27038011
TI  - Does the Biological Response to Fetal Hypoxia Involve Angiogenesis, Placental
      Enlargement and Preeclampsia?

PMID- 27038012
TI  - Making a difference? A comparison between multi-sensory and regular storytelling
      for persons with profound intellectual and multiple disabilities.
AB  - BACKGROUND: Multi-sensory storytelling (MSST) was developed to include persons
      with profound intellectual and multiple disabilities in storytelling culture. In
      order to increase the listeners' attention, MSST stories are individualised and
      use multiple sensory stimuli to support the verbal text. In order to determine
      the value of MSST, this study compared listeners' attention under two conditions:
      (1) being read MSST books and (2) being read regular stories. METHOD: A non
      randomised control study was executed in which the intervention group read MSST
      books (n = 45) and a comparison group (n = 31) read regular books. Books were
      read 10 times during a 5-week period. The 1st, 5th and 10th storytelling sessions
      were recorded on video in both groups, and the percentage of attention directed
      to the book and/or stimuli and to the storyteller was scored by a trained and
      independent rater. Two repeated measure analyses (with the storytelling condition
      as a between-subject factor and the three measurements as factor) were performed
      to determine the difference between the groups in terms of attention directed to
      the book/stimuli (first analysis) and storyteller (second analysis). A further
      analysis established whether the level of attention changed between the reading
      sessions and whether there was an interaction effect between the repetition of
      the book and the storytelling condition. RESULTS: The attention directed to the
      book and/or the stimuli was significantly higher in the MSST group than in the
      comparison group. No significant difference between the two groups was found in
      the attention directed to the storyteller. For MSST stories, most attention was
      observed during the fifth reading session, while for regular stories, the fifth
      session gained least attentiveness from the listener. CONCLUSION: The persons
      with profound intellectual and multiple disabilities paid more attention to the
      book and/or stimuli in the MSST condition compared with the regular story telling
      group. Being more attentive towards the book and stimuli might give persons with
      PIMD the opportunity to apprehend the story and to be included in storytelling
      culture.

PMID- 27038013
TI  - Trends in oral cavity cancer incidence, mortality, survival and treatment in the
      Netherlands.
AB  - Information on epidemiology is essential to evaluate care for the growing group
      of oral cancer patients. We investigated trends in incidence, mortality and
      relative survival rates for oral cavity cancer (OCC) and its subsites in the
      Netherlands from 1991 to 2010, and relate these to changes in stage and
      treatment. Patient (age, sex), tumour (subsite, stage) and treatment
      characteristics of patients diagnosed with OCC (ICD-O-3: C02-C06) in 1991-2010
      were extracted from the Netherlands Cancer Registry. Incidence, mortality and 5
      year relative survival rates over time are presented, as well as trends in type
      of treatment. The incidence of OCC increased with +1.2% (95%CI: +0.9%;+1.6%) per
      year: more strongly in women, stage I and IV disease, and in cancers of the
      tongue and gum. The mortality rate slightly rose (+0.8%, 95%CI: +0.3%;+1.3% per
      year), but differed by subsite. The 5-year relative survival improved from 57% in
      1991-1995 to 62% in 2006-2010. The 5-year relative survival was better for women
      compared with men (64% and 55%, respectively), decreased with increasing stage,
      was the best for tongue cancer (63%) and the worst for cancer of the gum (56%)
      and floor of mouth cancer (55%). The relative excess risk of dying was higher for
      non-surgery-based treatments. Surgery was the main treatment option and the
      proportion of "surgery only" rose in stage I and III disease. The incidence and,
      to a lesser extent, mortality of OCC are increasing and therefore, even with
      slightly improving survival rates, OCC is an increasingly important health
      problem.

PMID- 27038014
TI  - Comparison of P75 NTR-positive and -negative etcomesenchymal stem cell
      odontogenic differentiation through epithelial-mesenchymal interaction.
AB  - OBJECTIVES: The aim of this study was to investigate differences of odonto
      differentiation between P75 -neurotrophin receptor (P75 -NTR)-positive
      ectomesenchymal stem cells (P75+EMSCs) and P75 -NTR-negative ectomesenchymal stem
      cells (P75-EMSCs), and their underlying mechanisms. MATERIALS AND METHODS:
      Primary cranial neural crest-derived cells (CNC) were isolated from the first
      branchial arches, and P75+EMSCs and P75-EMSCs were sorted by fluorescence
      activated cell sorting. Differentiation of P75+EMSCs or P75-EMSCs into
      odontoblast-like cells was induced by dental epithelial cells in vitro or in
      vivo. Differential gene expression profiles between P75+EMSCs and P75-EMSCs were
      analysed by microarray assay. Smad4-specific small interfering RNA and activator
      kartogenin were used to treat the cells, to evaluate effects of Smad4 in odonto
      differentiation of P75+EMSCs or P75-EMSCs. RESULTS: Under induction of dental
      epithelium conditioned medium, P75+EMSCs had more mineralized node formation and
      higher expression of Dmp1 and Dspp compared to P75-EMSCs. In our in vivo study,
      graft of P75+EMSCs recombination with dental epithelium showed higher expression
      of DMP1 and DSP. Knock-down of Smad4 in P75+EMSCs significantly downregulated
      expression of DMP1 and DSP, while activation of Smad4 in P75-EMSCs by the
      activator kartogenin, significantly increased DSP and DMP1 expression.
      CONCLUSIONS: P75+EMSCs showed more odonto-differentiation potential than P75
      EMSCs both in vivo and in vitro. Smad4 played a critical role in determination of
      odonto-differentiation potential of CNC-derived EMSCs.

PMID- 27038015
TI  - Role of angiopoietin-2 in infection - A double-edged sword?
AB  - The endothelial angiopoietin (Angpt)/Tie2 ligand receptor system maintains
      vascular quiescence and modulates the response to injury. Angpt-1 is considered
      the natural Tie2 agonist and receptor ligation leads to its phosphorylation
      inducing various protective downstream pathways. The natural antagonist - Angpt-2
      - appears to inhibit these protective effects. In sepsis, the balance between
      both ligands is shifted in favor for Angpt-2 and the vasculature is highly
      dysfunctional, activated and leaky. Circulating levels of Angpt-2 strongly
      predict mortality in septic patients. Consistently, experimental strategies that
      target Angpt-2 (e.g. antibody, RNAi, etc.) can protect the vascular barrier and
      improve survival. However, in vitro is has also been shown that Angpt-2 can act
      as a dose-dependent Tie2 agonist/antagonist. Based on this, people have wondered
      if Angpt-2 is per se injurious or if it might have protective effects dependent
      on the scenario. A recent paper by Safioleas and colleagues showed survival
      benefits after a therapeutic injection of recombinant Angpt-2 in experimental
      pyelonephritis. Here, we discuss their counter-intuitive but interesting findings
      and put them into a global context with respect to the existent literature in the
      angiopoietin/Tie2 sepsis field.

PMID- 27038016
TI  - Thymoquinone ameliorated elevated inflammatory cytokines in testicular tissue and
      sex hormones imbalance induced by oral chronic toxicity with sodium nitrite.
AB  - Scientific evidence illustrated the health hazards of exposure to nitrites for
      prolonged time. Nitrites affected several body organs due to oxidative,
      inflammatory and apoptosis properties. Furthermore, thymoquinone (TQ) had
      curative effects against many diseases. We tried to discover the impact of both
      sodium nitrite and TQ on inflammatory cytokines contents in testicular tissues
      and hormonal balance both in vivo and in vitro. Fifty adult male SD rats received
      80mg/kg sodium nitrite and treated with either 25 or 50mg/kg TQ daily by oral
      gavage for twelve weeks. Testis were removed for sperms' count. Testicular tissue
      homogenates were used for assessment of protein and gene expression of IL-1beta,
      IL-6, TNF-alpha, Nrf2 and caspase-3. Serum samples were used for measurement of
      testosterone, LH, FSH and prolactin. Moreover, all the parameters were measured
      in human normal testis cell-lines, CRL-7002. Sodium nitrite produced significant
      decrease in serum testosterone associated with raised FSH, LH and prolactin.
      Moreover, sodium nitrite significantly elevated TNF-alpha, IL-1beta, IL-6,
      caspase-3 and reduced Nrf2. TQ significantly reversed all these effects both in
      vivo and in vitro. In conclusion, TQ ameliorated testicular tissue inflammation
      and restored the normal balance of sex hormones induced by sodium nitrite both in
      vivo and in vitro.

PMID- 27038017
TI  - Inhaled corticosteroids and HPA axis suppression: how important is it and how
      should it be managed?
AB  - Inhaled corticosteroids (ICS) are established as a cornerstone of management for
      patients with bronchoconstrictive lung disease. However, systemic absorption may
      lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis in a
      significant minority of patients. This is more likely in 'higher risk' patients
      exposed to high cumulative ICS doses, and in those treated with frequent oral
      corticosteroids or drugs which inhibit cytochrome p450 3A4. Hypothalamic
      pituitary-adrenal axis suppression is frequently unrecognized, such that some
      patients, notably children, only come to light when an adrenal crisis is
      precipitated by physical stress. To minimize this risk, 'higher risk' patients
      and those with previously identified suppressed cortisol responses to Synacthen
      testing should undergo an education programme to inform them about sick day
      rules. A review of ICS therapy should also be undertaken to ensure that the dose
      administered is the minimum required to control symptoms.

PMID- 27038018
TI  - Pollinator specialization: from the individual to the community.
AB  - 1190 I. 1190 II. 1191 III. 1191 IV. 1193 V. 1193 1194 References 1194 SUMMARY:
      Most spermatophytes need conspecific pollen in order to produce seed. This need
      for specialization seems to conflict with the generalized nature of most plant
      pollinator interactions. Specialization and generalization are dynamic - not
      fixed - and exist simultaneously in multiple states at different levels of
      biological hierarchy. Over the short term, specialization ensures conspecific
      pollen transfer, whereas over the long term, generalization improves system-level
      robustness. The balance between specialization and generalization at different
      scales is critical for different kinds of ecological functioning and is an
      important factor in plant speciation and the evolution of plant mating systems.
      Community context, including diversity and interaction network structure at
      different levels of aggregation, is a key driver of specialization dynamics.

PMID- 27038019
TI  - Behavioral activities collected through smartphones and the association with
      illness activity in bipolar disorder.
AB  - Smartphones are useful in symptom-monitoring in bipolar disorder (BD). Objective
      smartphone data reflecting illness activity could facilitate early treatment and
      act as outcome in efficacy trials. A total of 29 patients with BD presenting with
      moderate to severe levels of depressive and manic symptoms used a smartphone
      based self-monitoring system during 12 weeks. Objective smartphone data on
      behavioral activities were collected. Symptoms were clinically assessed every
      second week using the Hamilton Depression Rating Scale and the Young Mania Rating
      Scale. Objective smartphone data correlated with symptom severity. The more
      severe the depressive symptoms (1) the longer the smartphone's screen was
      "on"/day, (2) more received incoming calls/day, (3) fewer outgoing calls/day were
      made, (4) less answered incoming calls/day, (5) the patients moved less between
      cell towers IDs/day. Conversely, the more severe the manic symptoms (1) more
      outgoing text messages/day sent, (2) the phone calls/day were longer, (3) the
      fewer number of characters in incoming text messages/day, (4) the lower duration
      of outgoing calls/day, (5) the patients moved more between cell towers IDs/day.
      Further, objective smartphone data were able to discriminate between affective
      states. Objective smartphone data reflect illness severity, discriminates between
      affective states in BD and may facilitate the cooperation between patient and
      clinician. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27038020
TI  - The repeatability of an oral glucose test in ponies.
AB  - REASONS FOR PERFORMING STUDY: Insulin dysregulation can be difficult to diagnose
      from basal insulin and glucose concentrations, so a field-based oral glucose test
      (OGT) is preferred. However, the repeatability of this test has not been
      reported. OBJECTIVES: To determine the repeatability of an in-feed OGT in ponies
      and examine some factors affecting the palatability of the test meal. STUDY
      DESIGN: A repeated measures, longitudinal study. METHODS: An in-feed OGT was
      performed at 08.00 h on 3 consecutive occasions under controlled conditions in 8
      mixed breed ponies. d-glucose (0.75 g/kg bwt) was dissolved in water and combined
      with wheat bran and lucerne chaff. Blood samples were taken before and 90, 120,
      180 min and 24 h after d-glucose. The repeatability of the test was analysed with
      repeated measures ANOVA. Insulin and glucose responses to d-glucose were also
      compared to an equivalent dose of dietary carbohydrate provided with a commercial
      grain mixture. RESULTS: The overall insulin responses to the OGTs did not differ
      between tests. Individual insulin responses were more variable (P<0.05) than
      glucose responses. There was no difference in insulin concentration in post d
      glucose samples over time. Insulin and glucose responses to grain and d-Glucose
      were not different. CONCLUSIONS: An OGT is reasonably repeatable in ponies. The
      currently recommended post-glucose sampling time point of 2 h is acceptable, with
      sampling at 90 min also likely to produce a consistent result. The use of an
      alternative carbohydrate source to d-glucose, such as a commercial grain-based
      product, may be a viable and more palatable option for the test.

PMID- 27038021
TI  - Modularity and developmental stability in segmented animals: variation in
      translational asymmetry in geophilomorph centipedes.
AB  - Does a modular body organization present a challenge for developmental control?
      We investigate the idea of a possible developmental cost of modularity by
      examining the relationship between modularity and developmental stability in a
      multi-segmented arthropod taxon: the geophilomorph centipedes. In a sample of
      eight species, we tested the correlation between developmental stability,
      estimated from measures of translational fluctuating asymmetry, and the number of
      trunk segments and some other morphological traits, both at the species and
      individual levels. We found sizeable differences in size and shape patterns of
      variation at the level of species. However, we did not find any clear evidence of
      correlation between fluctuating asymmetry and the number of trunk segments or the
      other morphological traits considered. Thus, our results provide no support to
      the idea of a possible trade-off between the cardinality of a modular system and
      the level of developmental precision in the phenotypic expression of its modules.
      The results of this exploratory study invite further investigations of patterns
      of translational fluctuating asymmetry in segmented animals and other modular
      organisms, as these have the potential to reveal features of developmental
      stability that cannot be captured by the study of bilateral asymmetry alone.

PMID- 27038022
TI  - The sex-limited effects of mutations in the EGFR and TGF-beta signaling pathways
      on shape and size sexual dimorphism and allometry in the Drosophila wing.
AB  - Much of the morphological diversity in nature-including among sexes within a
      species-is a direct consequence of variation in size and shape. However,
      disentangling variation in sexual dimorphism for both shape (SShD), size (SSD),
      and their relationship with one another remains complex. Understanding how
      genetic variation influences both size and shape together, and how this in turn
      influences SSD and SShD, is challenging. In this study, we utilize Drosophila
      wing size and shape as a model system to investigate how mutations influence size
      and shape as modulated by sex. Previous work has demonstrated that mutations in
      epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF
      beta) signaling components can influence both wing size and shape. In this study,
      we re-analyze this data to specifically address how they impact the relationship
      between size and shape in a sex-specific manner, in turn altering the pattern of
      sexual dimorphism. While most mutations influence shape overall, only a subset
      have a genotypic specific effect that influences SShD. Furthermore, while we
      observe sex-specific patterns of allometric shape variation, the effects of most
      mutations on allometry tend to be small. We discuss this within the context of
      using mutational analysis to understand sexual size and shape dimorphism.

PMID- 27038023
TI  - Size, shape, and form: concepts of allometry in geometric morphometrics.
AB  - Allometry refers to the size-related changes of morphological traits and remains
      an essential concept for the study of evolution and development. This review is
      the first systematic comparison of allometric methods in the context of geometric
      morphometrics that considers the structure of morphological spaces and their
      implications for characterizing allometry and performing size correction. The
      distinction of two main schools of thought is useful for understanding the
      differences and relationships between alternative methods for studying allometry.
      The Gould-Mosimann school defines allometry as the covariation of shape with
      size. This concept of allometry is implemented in geometric morphometrics through
      the multivariate regression of shape variables on a measure of size. In the
      Huxley-Jolicoeur school, allometry is the covariation among morphological
      features that all contain size information. In this framework, allometric
      trajectories are characterized by the first principal component, which is a line
      of best fit to the data points. In geometric morphometrics, this concept is
      implemented in analyses using either Procrustes form space or conformation space
      (the latter also known as size-and-shape space). Whereas these spaces differ
      substantially in their global structure, there are also close connections in
      their localized geometry. For the model of small isotropic variation of landmark
      positions, they are equivalent up to scaling. The methods differ in their
      emphasis and thus provide investigators with flexible tools to address specific
      questions concerning evolution and development, but all frameworks are logically
      compatible with each other and therefore unlikely to yield contradictory results.

PMID- 27038024
TI  - Toward a study of gene regulatory constraints to morphological evolution of the
      Drosophila ocellar region.
AB  - The morphology and function of organs depend on coordinated changes in gene
      expression during development. These changes are controlled by transcription
      factors, signaling pathways, and their regulatory interactions, which are
      represented by gene regulatory networks (GRNs). Therefore, the structure of an
      organ GRN restricts the morphological and functional variations that the organ
      can experience-its potential morphospace. Therefore, two important questions
      arise when studying any GRN: what is the predicted available morphospace and what
      are the regulatory linkages that contribute the most to control morphological
      variation within this space. Here, we explore these questions by analyzing a
      small "three-node" GRN model that captures the Hh-driven regulatory interactions
      controlling a simple visual structure: the ocellar region of Drosophila. Analysis
      of the model predicts that random variation of model parameters results in a
      specific non-random distribution of morphological variants. Study of a limited
      sample of drosophilids and other dipterans finds a correspondence between the
      predicted phenotypic range and that found in nature. As an alternative to
      simulations, we apply Bayesian networks methods in order to identify the set of
      parameters with the largest contribution to morphological variation. Our results
      predict the potential morphological space of the ocellar complex and identify
      likely candidate processes to be responsible for ocellar morphological evolution
      using Bayesian networks. We further discuss the assumptions that the approach we
      have taken entails and their validity.

PMID- 27038025
TI  - Measurement error in geometric morphometrics.
AB  - Geometric morphometrics-a set of methods for the statistical analysis of shape
      once saluted as a revolutionary advancement in the analysis of morphology -is now
      mature and routinely used in ecology and evolution. However, a factor often
      disregarded in empirical studies is the presence and the extent of measurement
      error. This is potentially a very serious issue because random measurement error
      can inflate the amount of variance and, since many statistical analyses are based
      on the amount of "explained" relative to "residual" variance, can result in loss
      of statistical power. On the other hand, systematic bias can affect statistical
      analyses by biasing the results (i.e. variation due to bias is incorporated in
      the analysis and treated as biologically-meaningful variation). Here, I briefly
      review common sources of error in geometric morphometrics. I then review the most
      commonly used methods to measure and account for both random and non-random
      measurement error, providing a worked example using a real dataset.

PMID- 27038026
TI  - An anatomical study of wormian bones from the eastern part of India: is genetic
      influence a primary determinant of their morphogenesis?
AB  - Over the years a number of investigators have analysed the morphology of wormian
      bones in different population groups across the world. There have been
      significant variations between findings reported in these studies, and this has
      prompted researchers to focus on the influence of genetic factors on the
      morphology of these bones. In the light of the above observation, we considered
      it justified to conduct anatomical studies on wormian bones in different
      population groups; hence, we undertook the present study to look into the
      morphological details of these bones among a population in the eastern part of
      India. We observed a total of 120 adult dry human skulls of unknown age and sex,
      and noted the anatomical details of wormian bones when present. It was observed
      that wormian bones were present in 45 % of skulls, and that 30 % of skulls had
      more than one wormian bone. We also found that 2.5 % of the skulls had ten or
      more wormian bones, which is considered as pathognomonic. Maximum incidence
      (53.33 %) was observed at the lambdoid suture and minimum incidence at the bregma
      and metopic suture (0.61 % in each case). We noted a high incidence (21.21 %) of
      Inca bone/lambdoid ossicle, and bilaterally symmetrical wormian bones were
      present in 12.5 % study skulls. There were statistically significant (P < 0.05)
      variations between the findings of the present study and values reported in
      previous studies conducted in other regions of India and different parts of the
      world. Our observations favour the view that genetic influence primarily
      determines the morphology of wormian bones.

PMID- 27038027
TI  - In-vivo kinematics of high-flex posterior-stabilized total knee prosthesis
      designed for Asian populations.
AB  - PURPOSE: The purpose of this study was to determine in-vivo kinematics of our
      developed posterior-stabilized (PS) total knee prosthesis for Asian populations
      in comparison with a popular high-flexion PS prosthesis. METHODS: We analyzed 62
      osteoarthritic knees: 31 knees with the new PS prosthesis (group A) and 31 knees
      with a popular high-flexion PS prosthesis (group B). Radiographic knee images
      were taken during standing, lunge, and kneeling activities. The three-dimensional
      position and orientation of the implant components were determined using model
      based shape matching techniques. RESULTS: Group A showed slightly greater implant
      flexion angles compared with knees with conventional prosthesis at maximum lunge
      (average: 119 vs. 110 degrees , p = 0.001), and at maximum kneeling (121 vs. 114
      degrees , p = 0.004), although the range of motion was not significantly
      different. The femoral centre positions were more posterior in group A at
      standing, at 90 degrees  lunge, at maximum lunge (-9 and -7 mm, p = 0.004), at 90
      degrees  kneeling, and at maximum kneeling (-9 vs. -7 mm, p = 0.016), and
      posterior translations of the femoral center were greater at 90 degrees  knee
      flexion postures. The femoral centre positions had a strong negative correlation
      with implant flexion angles at maximum lunge in group B (r = -0.893, p < 0.001),
      but not in group A (p = 0.242). CONCLUSIONS: The new PS prosthesis designed for
      Asian knee morphology achieved flexion angles and range of motion at least
      comparable to that of conventional high-flexion PS prosthesis. The femoral roll
      back pattern, however, is different from a conventional knee, reflecting the
      post/cam design.

PMID- 27038028
TI  - Role of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus.
AB  - In the last ten years, knowledge on pathophysiology of type 2 diabetes (T2DM) has
      significantly increased, with multiple failures (decreased incretin effect,
      increased lipolysis, increased glucagon secretion, neurotransmitters dysfunction)
      recognized as important contributors, together with decreased insulin secretion
      and reduced peripheral glucose uptake. As a consequence, the pharmacologic
      therapy of T2DM has been progressively enriched by several novel classes of
      drugs, trying to overcome these defects. The last, intriguing compounds come into
      the market are SGLT2 inhibitors, framing the kidney in a different scenario, not
      as site of a harmful disease complication, but rather as the means to correct
      hyperglycemia and fight the disease. This review aims to offer a short, updated
      overview of the role of these compounds in the treatment of T2DM, focusing on
      efficacy, ancillary albeit relevant clinical effects, safety, potential
      cardiovascular protection, positioning in common therapeutic algorithms.

PMID- 27038029
TI  - Recommendations and guidelines in the JIMD: suggested procedures and avoidance of
      conflicts of interest.

PMID- 27038030
TI  - Clinical phenotype, biochemical profile, and treatment in 19 patients with
      arginase 1 deficiency.
AB  - BACKGROUND: Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD).
      This hypothesis-generating study explored clinical phenotypes, metabolic
      profiles, molecular genetics, and treatment approaches in a cohort of children
      and adults with ARG1 deficiency to add to our understanding of the underlying
      pathophysiology. METHODS: Clinical data were retrieved retrospectively from
      physicians using a questionnaire survey. Plasma aminoacids, guanidinoacetate
      (GAA), parameters indicating oxidative stress and nitric oxide (NO) synthesis as
      well as asymmetric dimethylarginine (ADMA) were measured at a single study site.
      RESULTS: Nineteen individuals with ARG1 deficiency and 19 matched controls were
      included in the study. In patients, paraparesis, cognitive impairment, and
      seizures were significantly associated suggesting a shared underlying
      pathophysiology. In patients plasma GAA exceeded normal ranges and plasma ADMA
      was significantly elevated. Compared to controls, nitrate was significantly
      higher, and the nitrite:nitrate ratio significantly lower in subjects with ARG1
      deficiency suggesting an advantage for NO synthesis by inducible NO synthase
      (iNOS) over endothelial NOS (eNOS). Logistic regression revealed no significant
      impact of any of the biochemical parameters (including arginine, nitrates, ADMA,
      GAA, oxidative stress) or protein restriction on long-term outcome. CONCLUSION:
      Three main hypotheses which must be evaluated in a hypothesis driven confirmatory
      study are delineated from this study: 1) clinical manifestations in ARG1
      deficiency are not correlated with arginine, protein intake, ADMA, nitrates or
      oxidative stress. 2) GAA is elevated and may be a marker or an active part of the
      pathophysiology of ARG1 deficiency. 3) Perturbations of NO metabolism merit
      future attention in ARG1 deficiency.

PMID- 27038031
TI  - Site-Specific N-Glycosylation of Recombinant Pentameric and Hexameric Human IgM.
AB  - Glycosylation is known to play an important role in IgG antibody structure and
      function. Polymeric IgM, the largest known antibody in humans, displays five
      potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a
      pentamer with a connecting singly N-glycosylated J-chain (with a total of 51
      glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the
      N-glycosylation of recombinant pentameric and hexameric IgM produced by the same
      human cell type and culture conditions was site-specifically profiled by RP-LC
      CID/ETD-MS/MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy
      of all putative N-glycosylation sites on the pentameric and hexameric IgM were
      able to be determined. Distinct glycosylation differences were observed between
      each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332,
      and Asn395 all had predominantly complex type glycans, differences in glycan
      branching and sialylation were observed between the sites. Asn563, a high mannose
      rich glycosylation site that locates in the center of the IgM polymer, was only
      approximately 60% occupied in both the pentameric and hexameric IgM forms, with a
      difference in relative abundance of the glycan structures between the pentamer
      and hexamer. This study highlights the information obtained by characterization
      of the site-heterogeneity of a highly glycosylated protein of high molecular mass
      with quaternary structure, revealing differences that would not be seen by global
      glycan or deglycosylated peptide profiling. Graphical Abstract ?.

PMID- 27038032
TI  - [Medical examination: preparation for ENT specialisation : Part 24].

PMID- 27038033
TI  - [Diagnosis of auditory processing disorders in children].
AB  - Despite normal hearing thresholds in pure tone audiometry, 0.5-1 % of children
      have difficulty understanding what they hear. An auditory processing disorder
      (APD) can be assumed, which should be clarified and treated. Based on a selective
      literature search in the PubMed and Scopus databases using the term "auditory
      processing disorder", several consensus papers are discussed. Numerous studies on
      APD have revealed partially contradicting results, thus fueling critical
      discussion regarding validity and reliability-of specific audiometric APD methods
      and the APD construct in particular. In order to correctly advise parents and,
      where necessary, treat affected children, otorhinolaryngologists, phoniatrists,
      and pediatric audiologists must understand the psychometric properties of applied
      tests and have knowledge of current discussion. Diagnosis is generally a
      multistep interdisciplinary process. 

PMID- 27038034
TI  - [Multicenter trial for sudden hearing loss therapy - planning and concept].
AB  - Systemic steroids are widely used worldwide as a standard of care for primary
      therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL
      guideline recommends high-dose steroids for primary therapy of ISSHL, without
      evidence from randomized controlled trials (RCTs). The rationale for the
      treatment of ISSHL using high dose steroids is only based on retrospective cohort
      studies.This article describes the planning and initiation of a multicenter,
      national, randomized, controlled clinical trial entitled Efficacy and safety of
      high dose glucocorticosteroid treatment for idiopathic sudden sensorineural
      hearing loss - a three-armed, randomized, triple-blind, multicenter trial
      (HODOKORT). This clinical trial aims to compare standard dose with two types of
      high-dose steroids for primary systemic therapy with respect to their efficacy in
      improving hearing, and thus communication ability, in patients with idiopathic
      sudden sensorineural hearing loss.This study is funded by the "Clinical Trials
      with High Patient Relevance" research program in the health research framework of
      the German Federal Ministry of Education and Research. It is one of two studies
      by the German Study Center of Clinical Trials of the German Society of
      Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was
      done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials
      of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the
      University Hospital Freiburg. 

PMID- 27038035
TI  - Severe scleroporphyria following autoimmune hepatitis.

PMID- 27038036
TI  - Alcohol preference and consumption are controlled by the caudal linear nucleus in
      alcohol-preferring rats.
AB  - The neuroanatomical and neurochemical basis of alcohol drinking has been
      extensively studied, but the neural circuitry mediating alcohol reinforcement has
      not been fully delineated. In the present experiments, we used both neuroimaging
      and pharmacological tools to identify neural systems associated with alcohol
      preference and high voluntary alcohol drinking in alcohol-preferring AA (Alko
      Alcohol) rats. First, we compared the basal brain activity of AA rats with that
      of heterogeneous Wistar rats with manganese-enhanced magnetic resonance imaging
      (MEMRI). Briefly, alcohol-naive rats were implanted with subcutaneous osmotic
      minipumps delivering 120 mg/kg MnCl2 over a 7-day period, and were then imaged
      using a three-dimensional rapid acquisition-relaxation enhanced pulse sequence.
      MEMRI analysis revealed that the most conspicuous subcortical activation
      difference was located in the caudal linear nucleus of raphe (CLi), with AA rats
      displaying significantly lower T1 signal in this region compared to Wistar rats.
      However, following long-term alcohol drinking, CLi activity was increased in AA
      rats. In the second experiment, the CLi was targeted with pharmacological tools.
      AA rats trained to drink 10% alcohol during 2-h sessions were implanted with
      guide cannulas aimed at the CLi and were given injections of the GABAA receptor
      agonist muscimol into the CLi before drinking sessions. Muscimol dose-dependently
      increased alcohol drinking, and co-administration of the gamma aminobutyric acid
      (GABA)A antagonist bicuculline blocked muscimol's effect. These findings suggest
      that the mediocaudal region of the ventral tegmental area, particularly the CLi,
      is important for the propensity for high alcohol drinking and controls alcohol
      reward via GABAergic transmission.

PMID- 27038037
TI  - Photoorganocatalytic One-Pot Synthesis of Hydroxamic Acids from Aldehydes.
AB  - An efficient one-pot synthesis of hydroxamic acids from aldehydes and
      hydroxylamine is described. A fast, visible-light-mediated metal-free
      hydroacylation of dialkyl azodicarboxylates was used to develop the subsequent
      addition of hydroxylamine hydrochloride. A range of aliphatic and aromatic
      aldehydes were employed in this reaction to give hydroxamic acids in high to
      excellent yields. Application of the current methodology was demonstrated in the
      synthesis of the anticancer medicine vorinostat.

PMID- 27038038
TI  - Corrigendum.
AB  - The complex role of NOTCH receptors and their ligands in the development of
      hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma by Borja Gil
      Garcia and Victoriano Baladron, Biol. Cell 2016, Vol 108, pages 29-40. DOI:
      10.1111/boc.201500029. In the following sentence on page 5 of this article a
      wrong reference was given: "Gramantieri et al. (2007) showed that the NOTCH1
      receptor causes growth inhibition and apoptosis of cell lines derived from HCC."
      This sentence should read: "Giovannini et al. (2012) showed that the
      downregulation of NOTCH1 receptor causes growth inhibition and induces senescence
      of cell lines derived from HCC." The correct reference is: Giovannini, C.,
      Gramantieri, L., Minguzzi, M., Fornari, F., Chieco, P., Grazi, G.L., Bolondi, L.
      (2012) CDKN1C/P57 is regulated by the Notch target gene Hes1 and induces
      senescence in human hepatocellular carcinoma. Am. J. Pathol. 181, 413-422

PMID- 27038039
TI  - Expanded criteria for retinopathy of prematurity screening in moderately preterm
      infants: Single-center pilot study.
AB  - BACKGROUND: While developed countries seek to lower the gestational age and
      birthweight parameters in retinopathy of prematurity (ROP) screening, older,
      larger infants still develop ROP in other parts of the world. The aim of this
      study was therefore to define criteria to identify potential ROP developers who
      are outliers of the common screening range. METHODS: A retrospective medical
      record review was performed in 147 inborn moderately preterm infants admitted to
      the neonatal intensive care unit during the study period. Univariate and logistic
      regression analysis was carried out. RESULTS: Forty-two infants developed ROP.
      Gestational age (31.4 +/- 1.1 vs 32.4 +/- 1.0 weeks, P = 0.000) and birthweight
      (1607.7 +/- 339.4 vs 1846.4 +/- 317.2 g, P = 0.000) were lower in those who
      developed ROP. Respiratory distress syndrome (P = 0.026) and documented sepsis (P
      = 0.003) were significant comorbidities on univariate analysis. Inotrope need >72
      h starting in the first week of life (P = 0.004; OR, 5.181) and more than three
      transfusions of packed red blood cells (P = 0.028; OR, 3.891) were also
      significant, both on univariate and multivariate analysis. CONCLUSIONS: In
      moderately preterm infants, status should be evaluated in order to effectively
      select candidates for ROP screening without missing potential ROP developers.

PMID- 27038040
TI  - ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal
      dissection of esophageal squamous cell carcinoma.
AB  - A previous genome-wide association study identified two novel esophageal squamous
      cell carcinoma (ESCC) susceptibility genes, ADH1B and ALDH2. We investigated the
      characteristics of ESCC, and the relationship between metachronous esophageal
      and/or pharyngeal squamous cell carcinoma (SCC) and the ADH1B & ALDH2 risk
      alleles. One hundred and seventeen superficial ESCC patients who underwent
      treatment with endoscopic submucosal dissection (ESD) were followed up using
      endoscopy for >=12 months. First, we performed a replication analysis to confirm
      the relationship between ESCC and the ADH1B & ALDH2 risk alleles using 117
      superficial ESCC cases and 1125 healthy controls. Next, we investigated the
      incidence and genetic/environmental factors associated with metachronous SCC
      development after ESD. We also analyzed the potential risk factors for
      metachronous SCC development using Cox's proportional hazards model. rs1229984 GG
      located on ADH1B and rs671 GA located on ALDH2 were significantly associated with
      ESCC progression (P = 7.93 * 10(-4) and P = 1.04 * 10(-5) ). Patients with
      rs1229984 GG, those with rs671 GA, smokers, heavy alcohol drinkers (44 g/day
      ethanol), and presence of multiple Lugol-voiding lesions (LVLs) developed
      metachronous SCC more frequently (P = 3.20 * 10(-3) , 7.00 * 10(-4) , 4.00 * 10(
      4) , 2.15 * 10(-2) , and 4.41 * 10(-3) , respectively), with hazard ratios were
      2.84 (95% confidence interval [CI] = 1.43-5.63), 4.57 (95% CI = 1.80-15.42), 4.84
      (95% CI = 1.89-16.41), and 2.34 (95% CI = 1.12-5.31), respectively. Multiple
      logistic regression analysis revealed that rs1229984 GG, rs671 GA, and smoking
      status were independently associated with the risk of developing metachronous
      SCCs after ESD. Moreover, we found cumulative effects of these two genetic
      factors (rs1229984 GG and rs671 GA) and one environmental factor (tobacco
      smoking) which appear to increase metachrous SCCs after ESD of ESCC risk
      approximately nearly 12-fold. Our findings elucidated the crucial role of
      multiple genetic variations in ADH1B and ALDH2 as biomarkers of metachronous
      ESCC.

PMID- 27038041
TI  - Edge Functionalization of Graphene and Two-Dimensional Covalent Organic Polymers
      for Energy Conversion and Storage.
AB  - Edge functionalization by selectively attaching chemical moieties at the edge of
      graphene sheets with minimal damage of the carbon basal plane can impart
      solubility, film-forming capability, and electrocatalytic activity, while largely
      retaining the physicochemical properties of the pristine graphene. The resultant
      edge-functionalized graphene materials (EFGs) are attractive for various
      potential applications. Here, a focused, concise review on the synthesis of EFGs
      is presented, along with their 2D covalent organic polymer (2D COP) analogues, as
      energy materials. The versatility of edge-functionalization is revealed for
      producing tailor-made graphene and COP materials for efficient energy conversion
      and storage. 

PMID- 27038042
TI  - Moraxella catarrhalis induces CEACAM3-Syk-CARD9-dependent activation of human
      granulocytes.
AB  - The human restricted pathogen Moraxella catarrhalis is an important causal agent
      for exacerbations in chronic obstructive lung disease in adults. In such
      patients, increased numbers of granulocytes are present in the airways, which
      correlate with bacteria-induced exacerbations and severity of the disease. Our
      study investigated whether the interaction of M. catarrhalis with the human
      granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule
      (CEACAM)-3 is linked to NF-kappaB activation, resulting in chemokine production.
      Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis
      in the presence of different inhibitors, blocking antibodies and siRNA. The
      supernatants were analysed by enzyme-linked immunosorbent assay for chemokines.
      NF-kappaB activation was determined using a luciferase reporter gene assay and
      chromatin-immunoprecipitation. We found evidence that the specific engagement of
      CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the
      activation of pro-inflammatory events, such as degranulation of neutrophils, ROS
      production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced
      the activation of the NF-kappaB pathway via Syk and the CARD9 pathway and was
      dependent on the phosphorylation of the CEACAM3 ITAM-like motif. These findings
      suggest that the CEACAM3 signalling in neutrophils is able to specifically
      modulate airway inflammation caused by infection with M. catarrhalis.

PMID- 27038043
TI  - MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton
      spin density.
AB  - PURPOSE: To introduce a two-dimensional MR fingerprinting (MRF) technique for
      quantification of T1 , T2 , and M0 in myocardium. METHODS: An electrocardiograph
      triggered MRF method is introduced for mapping myocardial T1 , T2 , and M0 during
      a single breath-hold in as short as four heartbeats. The pulse sequence uses
      variable flip angles, repetition times, inversion recovery times, and T2
      preparation dephasing times. A dictionary of possible signal evolutions is
      simulated for each scan that incorporates the subject's unique variations in
      heart rate. Aspects of the sequence design were explored in simulations, and the
      accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo
      imaging was performed at 3 Tesla in 11 volunteers to generate native parametric
      maps. RESULTS: T1 and T2 measurements from the proposed cardiac MRF sequence
      correlated well with standard spin echo measurements in the phantom study (R2  >
      0.99). A Bland-Altman analysis revealed good agreement for myocardial T1
      measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72
      ms) and T2 measurements between MRF and T2 -prepared balanced steady-state free
      precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). CONCLUSION:
      MRF can provide quantitative single slice T1 , T2 , and M0 maps in the heart
      within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27038044
TI  - Dietary Pyridoxine Protects against Stress and Maintains Immunohaematological
      Status in Chanos chanos Exposed to Endosulfan.
AB  - The amelioration effect of water-soluble vitamin pyridoxine against stress was
      evaluated in milkfish, Chanos chanos exposed to endosulfan. Two hundred and
      twenty-five fish were distributed randomly into five treatments, each with three
      replicates. Four isocaloric and isonitrogenous diets with graded levels of
      pyridoxine feed were as follows: normal water and fed with control diet
      (En0/PY0); endosulfan-treated water and fed with control diet (En/PY0); and
      endosulfan-treated water and fed with 50 (En/PY 50 mg/kg), 75 (En/PY 75 mg/kg)
      and 100 mg/kg (En/PY 100 mg/kg) pyridoxine-supplemented feed. The endosulfan in
      treated water was maintained at a level of 1/40th of LC50 (0.52 ppb). The effect
      of dietary pyridoxine supplementation was studied in terms of antioxidative
      enzymes (catalase, superoxide dismutase, glutathione-S-transferase), stress
      markers [heat-shock protein 70, caspase-3, cortisol, acetylcholine esterase
      (AChE), blood glucose], immunohaematological parameters (total protein, albumin,
      globulin and A/G ratio, nitroblue tetrazolium, RBC, WBC, Hb), gill histopathology
      and a subsequent challenge study with Vibrio parahaemolyticus. The antioxidative
      enzymes, stress markers, albumin and A/G ratio were significantly (p < 0.01)
      elevated, brain AChE and immunohaematological parameters were significantly (p <
      0.01) decreased, and chromosome aberration and gill histopathology were also
      altered due to endosulfan exposure. The relative survival % was reduced due to
      the combined effect of endosulfan stress and bacterial challenge. Fish fed the
      diet supplemented with pyridoxine at 75 and 100 mg/kg was found to restore the
      studied parameter towards normal compared with control and indicated protection
      against endosulfan-induced stress significantly (p < 0.01). Results obtained in
      the present study indicate that the supplementation of 75 and 100 mg/kg of
      pyridoxine in the diet has a definitive role in the mitigation of the endosulfan
      induced stress in milkfish, C. chanos fingerlings. 

PMID- 27038045
TI  - Impacts of Supervised Exercise Training in Addition to Interdisciplinary
      Lifestyle Management in Subjects Awaiting Bariatric Surgery: a Randomized
      Controlled Study.
AB  - BACKGROUND: Experts recommend physical activity (PA) to optimize bariatric
      surgery (BS) results. However, evidence on the effect of PA before BS is missing.
      The aim of this study was to assess the impact of adding a Pre-Surgical Exercise
      Training (PreSET) to an interdisciplinary lifestyle intervention on physical
      fitness, quality of life, PA barriers, and anthropometric parameters of subjects
      awaiting BS. METHODS: Thirty candidates for BS (43.2 +/- 9.2 years, 47.5 +/- 8.1
      kg/m2) have been randomized in two groups: one group following the PreSET
      (endurance and strength training) and another receiving usual care. Before and
      after 12 weeks, we assessed physical fitness with a battery of tests (symptom
      limited exercise test, 6-min walk test (6MWT), sit-to-stand test, half-squat
      test, and arm curl test), quality of life with the laval questionnaire, and PA
      barriers with the physical exercise belief questionnaire. RESULTS: One control
      group subject abandoned the study. Subjects in the PreSET group participated in
      60.0 % of the supervised exercise sessions proposed. Results showed significant
      improvements in the 6MWT (17.4 +/- 27.2 vs. -16.4 +/- 42.4 m; p = 0.03), half
      squat test (17.1 +/- 17.9 vs. -0.9 +/- 14.5 s; p = 0.05), arm curl repetitions
      (4.8 +/- 2.3 vs. 1.0 +/- 4.1; p = 0.01), social interaction score (10.7 +/- 12.5
      vs. -2.1 +/- 11.0 %; p = 0.02), and embarrassment (-15.6 +/- 10.2 vs. -3.1 +/-
      17.8 %; p = 0.02) in completers (n = 8) compared to the non-completers (n = 21).
      No significant difference between groups in BMI and other outcomes studied was
      observed after the intervention. CONCLUSIONS: Adding a PreSET to an individual
      lifestyle counselling intervention improved physical fitness, social
      interactions, and embarrassment. Post-surgery data would be interesting to
      confirm these benefits on the long term.

PMID- 27038046
TI  - Patient-Reported Adherence to Empiric Vitamin/Mineral Supplementation and Related
      Nutrient Deficiencies After Roux-en-Y Gastric Bypass.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is associated with nutrient
      deficiencies, but the optimal supplement regimen remains unclear. We assessed
      patient-reported adherence to and efficacy of Mayo Clinic's post-RYGB
      vitamin/mineral supplement protocol and the related incidence of common nutrient
      deficiencies. METHODS: Data were collected on 287 obese patients who underwent
      RYGB. Patient-reported supplement adherence was assessed via
      medication/supplement lists generated by medication reconciliation in hospital
      dismissal summaries and clinic notes at 6, 12, and 18-36 months postsurgery.
      Deficiencies were assessed via measurements of hemoglobin, ferritin, 25
      hydroxyvitamin D, and vitamins A, E, and B12 in the setting of our
      supplementation protocol. RESULTS: Patient-reported adherence to
      multivitamin/minerals and subcutaneous vitamin B12 was sustained in >92 % of
      patients, correlating with low rates of vitamin A, E, and B12 deficiencies (4.9,
      0, and 3.7 %, respectively). Rates of calcium supplementation decreased (94.1 to
      78.7 %) while rates of vitamin D and iron use increased over time (39.7 to 65.8
      and 6.3 to 23.1 %, respectively). At 18-36 months, vitamin D deficiency persisted
      in 16.2 % of patients, iron deficiency in 6.7 % of women and 17.2 % of men, and
      anemia in 12.2 % of women and 34.3 % of men. CONCLUSION: Compared to previous
      reports, we found a lower prevalence of micronutrient deficiencies and excellent
      patient-reported adherence to a standardized multivitamin/mineral and vitamin B12
      regimen. Continued prevalence of vitamin D deficiency prompts consideration of
      standardized vitamin D supplementation after RYGB. Anemia and iron deficiency
      were observed at lower rates than previously reported, but were more common in
      men compared to women.

PMID- 27038047
TI  - Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases
      Intestinal Gluconeogenesis in a T2DM Rat Model.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment
      for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the
      effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal
      morphological adaption, as well as hepatic and intestinal gluconeogenesis.
      METHODS: Twenty adult male T2DM rats induced by high-fat diet and low dose of
      streptozotocin were randomly divided into sham and RYGB groups. The parameters of
      body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid
      profiles were assessed to evaluate metabolic changes. Intestinal sections were
      stained with hematoxylin and eosin (H&E) for light microscopy examination. The
      messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of
      gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase
      (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western
      blotting, respectively. RESULTS: RYGB induced significant improvements in glucose
      tolerance and insulin sensitivity, along with weight loss and decreased food
      intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA)
      levels. The jejunum and ileum exhibited a marked increase in the length and
      number of intestinal villi after RYGB. The RYGB group exhibited downregulated
      mRNA and protein expression levels of PEPCK and G6Pase in the liver and
      upregulated expression of these enzymes in the jejunum and ileum tissues.
      CONCLUSIONS: RYGB ameliorates glucose and lipid metabolism accompanied by weight
      loss and calorie restriction. The small intestine shows hyperplasia and
      hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced
      hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute
      to improved glucose homeostasis after RYGB.

PMID- 27038049
TI  - Ghost busting--taking the sheet off the ghost.

PMID- 27038050
TI  - The Coping Long Term with Active Suicide Program: Description and Pilot Data.
AB  - A description of and pilot data for a new adjunctive intervention designed to
      reduce suicidal behavior among high-risk individuals are presented. The Coping
      Long Term with Active Suicide Program (CLASP) has three major components: (1)
      three individual, in-person meetings, (2) one significant other/family meeting,
      and (3) 11 brief (15-30 minute) phone contacts with the patient and his/her
      significant other. Open trial and pilot randomized trial data provide preliminary
      evidence that CLASP is a feasible, acceptable, and efficacious intervention to
      reduce suicidal behavior.

PMID- 27038051
TI  - The Influence of Active Carbon Supports Toward the Electrocatalytic Behavior of
      Fe3O4 Nanoparticles for the Extended Energy Generation of Mediatorless Microbial
      Fuel Cells.
AB  - Magnetite (Fe3O4) nanoparticles anchored over the different active carbon
      supports were developed by a simple wet solution method. The developed
      nanostructures were magnetically self-assembled over the electrode surface and
      exploited as anode catalysts in mediatorless microbial fuel cells (MFC). The
      morphological characterizations revealed that 3~8-nm-sized Fe3O4 nanoparticles
      were homogeneously anchored over the different carbon matrices and the obtained
      diffraction patterns ensured the cubic inverse spinel structure of prepared Fe3O4
      nanoparticles. The morphology, size, and structure of Fe3O4 nanoparticles
      anchored over the different active carbon supports were maintained identical, and
      the influence of active carbon support toward the effectual MFC performances was
      evaluated under various electrochemical regimes and conditions by using
      Escherichia coli as a catalytic microorganism. The electrochemical
      characterizations revealed that carbon nanotube (CNT)-supported Fe3O4
      nanoparticles exhibited lower charge transfer resistance and high coulombic
      efficiency in comparison with the graphene and graphite nanofiber-supported
      composites. Among the studied anode catalysts, Fe3O4/CNT composite exhibited the
      maximum MFC power density of 865 mW m(-2) associated with excellent durability
      performances, owing to the specific interaction exerted between the
      microorganisms and the Fe3O4/CNT composite. Thus, the binder-free electrode
      modification process, mediatorless environment, rapid electron transfer kinetics,
      high power generation, and long durability performances achieved for the
      developed system paved futuristic dimensions for the high performance MFCs. 

PMID- 27038052
TI  - Silk fibroin hydrogel as physical barrier for prevention of post hernia adhesion.
AB  - BACKGROUND: Adhesion formation remains a major complication following hernia
      repair surgery. Physical barriers though effective for adhesion prevention in
      clinical settings are associated with major disadvantages, therefore, needs
      further investigation. This study evaluates silk fibroin hydrogel as a physical
      barrier on polypropylene mesh for the prevention of adhesion following ventral
      hernia repair. STUDY DESIGN: Peritoneal explants were cultured on silk fibroin
      scaffold to evaluate its support for mesothelial cell growth. Full thickness
      uniform sized defects were created on the ventral abdominal wall of rabbits, and
      the defects were covered either with silk hydrogel coated polypropylene mesh or
      with plain polypropylene mesh as a control. The animals were killed after 1
      month, and the adhesion formation was graded; healing response of peritoneum was
      evaluated by immunohistochemistry with calretinin, collagen staining of
      peritoneal sections, and expression of PCNA, collagen-I, TNFalpha, IL6 by real
      time PCR; and its adverse effect if any was determined. RESULTS: Silk fibroin
      scaffold showed excellent support for peritoneal cell growth in vitro and the
      cells expressed calretinin. A remarkable prevention of adhesion formation was
      observed in the animals implanted with silk hydrogel coated mesh compared to the
      control group; in these animals peritoneal healing was complete and predominantly
      by mesothelial cells with minimum fibrotic changes. Expression of inflammatory
      cytokines decreased compared to control animals, histology of abdominal organs,
      haematological and blood biochemical parameters remained normal. CONCLUSION:
      Therefore, silk hydrogel coating of polypropylene mesh can improve peritoneal
      healing, minimize adhesion formation, is safe and can augment the outcome of
      hernia surgery.

PMID- 27038053
TI  - How to perform the endoscopically assisted components separation technique (ECST)
      for large ventral hernia repair.
AB  - BACKGROUND: The components separation technique (CST) is frequently used for
      reconstructing large ventral hernias. Unfortunately, it is associated with a high
      wound complication rate up to 50 %, caused by large wound surface and inherent
      trauma to abdominal skin vascularization. An endoscopically assisted modification
      of the original technique (ECST) spares skin vascularization and reduces wound
      surface, supposedly reducing wound complications. This study accurately describes
      ECST step by step with detailed illustrations and report the results of a 27
      patient cohort. METHODS: Since September 2012 patients with midline hernias
      without previous subcutaneous dissection and a maximum diameter of approximately
      10-15 cm underwent ECST in an expert centre for abdominal wall reconstructions.
      Prospective data was gathered during inpatient care and 3-6 monthly follow-up.
      RESULTS: Twenty-seven patients (17 male/10 female) with median age of 60 years
      (range 35-77), average BMI 27 (SD +/-2) kg/m(2) and median ASA classification 2
      (range 1-3) underwent ECST. Two patients were excluded due to bilateral
      conversion to conventional CST and finding of peritoneal metastases. Median
      defect size was 116 +/- 48 cm(2). Median length of stay was 5 days (range 3-15).
      Wound complication rate was 11 %. Recurrence rate was 29 % after a median follow
      up of 13 months. CONCLUSIONS: Endoscopically assisted modification of the
      original technique can be used for reconstructing large and complex ventral
      hernias up to 15 cm in diameter. The results of this small sized cohort study
      showed that ECST is feasible in patients with a uro-, or enterostomy and suggest
      that ECST reduces wound complication rate when compared to CST.

PMID- 27038054
TI  - HDQLIFE: the development of two new computer adaptive tests for use in Huntington
      disease, Speech Difficulties, and Swallowing Difficulties.
AB  - PURPOSE: Huntington disease (HD) is an autosomal dominant neurodegenerative
      disease which results in several progressive symptoms, including bulbar
      dysfunction (i.e., speech and swallowing difficulties). Although difficulties in
      speech and swallowing in HD have a negative impact on health-related quality of
      life, no patient-reported outcome measure exists to capture these difficulties
      that are specific to HD. Thus, we developed a new patient-reported outcome
      measure for use in the Huntington Disease Health-Related Quality of Life
      (HDQLIFE) Measurement System that focused on the impact that difficulties with
      speech and swallowing have on HRQOL in HD. METHODS: Five hundred and seven
      individuals with prodromal and/or manifest HD completed 47 newly developed items
      examining speech and swallowing difficulties. Unidimensional item pools were
      identified using exploratory factor analysis and confirmatory factor analysis
      (EFA and CFA, respectively). Item response theory (IRT) was used to calibrate the
      final measures. RESULTS: EFA and CFA identified two separate unidimensional sets
      of items: Speech Difficulties (27 items) and Swallowing Difficulties (16 items).
      Items were calibrated separately for these two measures and resulted in item
      banks that can be administered as computer adaptive tests (CATs) and/or 6-item,
      static short forms. Reliability of both of these measures was supported through
      high correlations between the simulated CAT scores and the full item bank.
      CONCLUSIONS: CATs and 6-item calibrated short forms were developed for HDQLIFE
      Speech Difficulties and HDQLIFE Swallowing Difficulties. These measures both
      demonstrate excellent psychometric properties and may have clinical utility in
      other populations where speech and swallowing difficulties are prevalent.

PMID- 27038055
TI  - Streptavidin conjugation and quantification-a method evaluation for
      nanoparticles.
AB  - Aiming at the development of validated protocols for protein conjugation of
      nanomaterials and the determination of protein labeling densities, we
      systematically assessed the conjugation of the model protein streptavidin (SAv)
      to 100-, 500-, and 1000-nm-sized polystyrene and silica nanoparticles and dye
      encoded polymer particles with two established conjugation chemistries, based
      upon achievable coupling efficiencies and labeling densities. Bioconjugation
      reactions compared included EDC/sulfo NHS ester chemistry for direct binding of
      the SAv to carboxyl groups at the particle surface and maleimide-thiol chemistry
      in conjunction with heterobifunctional PEG linkers and aminated nanoparticles
      (NPs). Quantification of the total and functional amounts of SAv on these
      nanomaterials and unreacted SAv in solution was performed with the BCA assay and
      the biotin-FITC (BF) titration, relying on different signal generation
      principles, which are thus prone to different interferences. Our results revealed
      a clear influence of the conjugation chemistry on the amount of NP crosslinking,
      yet under optimized reaction conditions, EDC/sulfo NHS ester chemistry and the
      attachment via heterobifunctional PEG linkers led to comparably efficient SAv
      coupling and good labeling densities. Particle size can obviously affect protein
      labeling densities and particularly protein functionality, especially for larger
      particles. For unstained nanoparticles, direct bioconjugation seems to be the
      most efficient strategy, whereas for dye-encoded nanoparticles, PEG linkers are
      to be favored for the prevention of dye-protein interactions which can affect
      protein functionality specifically in the case of direct SAv binding. Moreover,
      an influence of particle size on achievable protein labeling densities and
      protein functionality could be demonstrated. 

PMID- 27038056
TI  - A novel four-dimensional analytical approach for analysis of complex samples.
AB  - A two-dimensional LC (2D-LC) method, based on the work of Erni and Frei in 1978,
      was developed and coupled to an ion mobility-high-resolution mass spectrometer
      (IM-MS), which enabled the separation of complex samples in four dimensions (2D
      LC, ion mobility spectrometry (IMS), and mass spectrometry (MS)). This approach
      works as a continuous multiheart-cutting LC system, using a long modulation time
      of 4 min, which allows the complete transfer of most of the first - dimension
      peaks to the second - dimension column without fractionation, in comparison to
      comprehensive two-dimensional liquid chromatography. Hence, each compound
      delivers only one peak in the second dimension, which simplifies the data
      handling even when ion mobility spectrometry as a third and mass spectrometry as
      a fourth dimension are introduced. The analysis of a plant extract from Ginkgo
      biloba shows the separation power of this four-dimensional separation method with
      a calculated total peak capacity of more than 8700. Furthermore, the advantage of
      ion mobility for characterizing unknown compounds by their collision cross
      section (CCS) and accurate mass in a non-target approach is shown for different
      matrices like plant extracts and coffee. Graphical abstract Principle of the four
      dimensional separation.

PMID- 27038057
TI  - A rapid and sensitive method for kinetic study and activity assay of DNase I in
      vitro based on a GO-quenched hairpin probe.
AB  - As a waste-management endonuclease, DNase I has been suggested to be one of the
      deoxyribonucleases responsible for DNA fragmentation during apoptosis. We report
      here an alternative fluorescence method for DNase I assay with high accuracy and
      sensitivity by applying a DNA/GO (graphene oxide) probe. The method with a
      detection limit of 1 U mL(-1) was then applied to investigate the effects of
      external factors including antibiotics and heavy metal ions on DNase I. The
      results demonstrated that gentamicin sulfate was a strong inhibitor with an IC50
      value of 0.57 +/- 0.12 mM. The investigated heavy metal ions showed an inhibitory
      effect on DNase I activity in a concentration dependent manner with IC50 values
      of 0.04 MUg/mL (Hg(2+)), 0.10 MUg/mL (Pb(2+)), 1.35 MUg/mL (Cd(2+)), 1.20 MUg/mL
      (As(2+)), and 1.80 MUg/mL (Cu(2+)). Finally, the new method was applied to detect
      DNase levels in complicated tumor tissue and cell samples and the results showed
      that DNase levels increased in tumor tissues compared with that of adjacent
      tissue. From the above results, we conclude that the method can be widely used
      for high - throughput assay of DNase I in biological samples as well as drug
      screening in vitro. Graphical Abstract The schematic of real-time monitoring of
      DNase I using GO - quenched hairpin probe as the substrate. The process of
      nucleotide digestion catalyzed by DNase I produces short fragments of hairpin
      probe and accordingly causes a significant increase in fluorescence. At first, GO
      can absorb the hairpin probes and quenched their fluorescence. When there is
      DNase I, the DNase can cleave the double strands of DNA. Fluorescence is restored
      due to the significantly weaker binding ability of small DNA fragments to GO
      compared with long DNA fragments. So, we can detect the increase in fluorescence
      to study the activity of DNase.

PMID- 27038058
TI  - Hasse diagram as a green analytical metrics tool: ranking of methods for
      benzo[a]pyrene determination in sediments.
AB  - This study presents an application of the Hasse diagram technique (HDT) as the
      assessment tool to select the most appropriate analytical procedures according to
      their greenness or the best analytical performance. The dataset consists of
      analytical procedures for benzo[a]pyrene determination in sediment samples, which
      were described by 11 variables concerning their greenness and analytical
      performance. Two analyses with the HDT were performed-the first one with
      metrological variables and the second one with "green" variables as input data.
      Both HDT analyses ranked different analytical procedures as the most valuable,
      suggesting that green analytical chemistry is not in accordance with metrology
      when benzo[a]pyrene in sediment samples is determined. The HDT can be used as a
      good decision support tool to choose the proper analytical procedure concerning
      green analytical chemistry principles and analytical performance merits.

PMID- 27038059
TI  - Patients' perceptions of mortality risk for localized prostate cancer vary
      markedly depending on their treatment strategy.
AB  - Treatment choice for localized prostate cancer (PCa) is a controversial issue,
      and mortality risk is probably the most decisive factor in this regard. The study
      aimed to compare prostate-cancer-specific mortality risk estimates for different
      treatment options assigned by patients managed with active surveillance (AS),
      radical prostatectomy (RP) and patients who had discontinued AS (DAS). Patients
      initially managed with AS or RP (N = 370) were matched according to length of
      therapy. All patients completed mailed questionnaires assessing their mortality
      risk estimates (in %) and prostate-cancer-specific anxiety. Differences in risk
      estimates among the three treatment groups were analyzed using ANOVA,
      relationships of clinical and psychosocial variables with risk estimates using
      standard multiple regression. In all treatment groups, the prostate- cancer
      specific mortality risk was overestimated. This applied whether it was the
      patient's own treatment or the alternative treatment option. RP patients assigned
      a mortality risk to AS that was almost three times higher than that assigned to
      RP (50.9 +/- 25.0 vs. 17.8 +/- 19.7, d = 1.48; p < 0.001). Anxiety was
      significantly associated with risk estimates for AS (p = 0.008) and RP (p =
      0.001). Compared with clinical data that suggest that the prostate-cancer
      specific mortality risk for AS is low and does not significantly differ from that
      for RP, patients strongly overestimated the mortality risk. This was most
      markedly so in RP patients, who drastically overestimated the benefits of RP
      compared to the risk of AS. This overestimation could increase overtreatment and
      should therefore be corrected by better patient education. 

PMID- 27038060
TI  - Association between gross motor function and nutritional status in children with
      cerebral palsy: a cross-sectional study from Colombia.
AB  - AIM: To determine the association between gross motor function and nutritional
      status in children with cerebral palsy (CP) residing in an urban area in a
      developing country. METHOD: We conducted a cross-sectional study in 177 children
      (ages 2-12y, 59.3% male) with a diagnosis of CP who were attending rehabilitation
      centres in Bucaramanga, Colombia (2012-2013). A physiotherapist evaluated
      patients using the Gross Motor Function Classification System (GMFCS, levels I to
      V). Nutritional status was evaluated by nutritionists and classified according to
      the World Health Organization growth charts. We used linear and multinomial
      logistic regression methods to determine the associations. RESULTS: There were
      39.5%, 6.8%, 5.6%, 16.4%, and 31.6% patients classified in levels I to V
      respectively. The mean adjusted differences for weight-for-age, height-for-age,
      BMI-for-age, and height-for-weight z-scores were significantly larger for
      children classified in levels II to V compared with those in level I. The
      children classified in levels IV and V were more likely to have malnutrition
      (adjusted odds ratio [OR] 5.64; 95% confidence interval [CI] 2.27-14.0) and
      stunting (OR 8.42; 95% CI 2.90-24.4) than those classified in GMFCS levels I to
      III. INTERPRETATION: Stunting and malnutrition are prevalent conditions among
      paediatric patients with CP, and both are directly associated with higher levels
      of gross motor dysfunction.

PMID- 27038061
TI  - Quality of Life Following Symptomatic Macromastia Surgery: Short- and Long-term
      Evaluation.
AB  - Mammary hypertrophy or macromastia can cause a wide range of symptoms (physical,
      psychosomatic or behavioral), which affect patients' quality of life. Breast
      reduction can, in most of the cases, solve the problem. However, certain factors
      could have a negative effect on the outcome of surgery. The aims of this study
      were to discover the degree of patient satisfaction (short- and long-term) and to
      evaluate results of reduction mammoplasty, and also to ascertain which factors
      may have a negative role on the effectiveness of breast reduction surgery. We
      carried out a prospective and longitudinal study of 121 patients who underwent
      breast reduction surgery. Quality of life, outcome of surgery (complications and
      sequelae) and degree of patient satisfaction were evaluated at 1 month and at 1
      year after reduction mammoplasty. Mean patient age was 40.71 (SD = 12.02). Among
      them, 35.5% were overweight, 44.6% were obese and 34.7% were smokers. The most
      common symptom was pain. The mean amount of resected breast tissue was 1785 g (SD
      = 876). A total of 27.3% of the patients suffered complications and 30.60%
      suffered sequelae. Our results show an improvement in symptoms (p < 0.001) and
      quality of life (p < 0.001 to p = 0.002) 1 month after and 1 year after breast
      reduction compared with the preoperative situation. Neither age, body mass index,
      smoking habit nor the amount of tissue removed had a negative effect on the
      results of surgery. One year after surgery, the majority of patients were
      satisfied with the outcome (96.6%), they would recommend it to others (96.6%),
      and they would undergo surgery a second time (95.8%). CONCLUSIONS: Breast
      reduction is highly efficient in resolving symptoms and in improving quality of
      life. It leads to a high level of short- and long-term satisfaction irrespective
      of each patient's individual characteristics.

PMID- 27038062
TI  - Organocatalytic Enantioselective Synthesis of Pyrazoles Bearing a Quaternary
      Stereocenter.
AB  - An efficient one-pot asymmetric synthesis of pyrazoles bearing a chiral
      quaternary stereocenter has been developed. Quinine-derived thiourea catalyzed
      the enantioselective addition of pyrazolones to isatin-derived ketimines,
      providing the corresponding acetylated pyrazoles after in situ treatment with Ac2
      O/Et3 N. The corresponding pyrazoles were afforded in high yields and excellent
      enantioselectivities.

PMID- 27038063
TI  - Surveys and objectifying the subjective.

PMID- 27038064
TI  - Use of Direct-Acting Oral Anticoagulants in Nonagenarians: A Call for More Data.
AB  - The prevalence and embolic risk of atrial fibrillation (AF) increase with age.
      Vitamin K antagonists (VKAs) or direct-acting oral anticoagulants (DOACs) reduce
      the risk of stroke or embolism. The aim of this review was to summarize the
      paucity of information regarding the safety and efficacy of DOACs in AF patients
      aged 90 years or older. The maximum age of included patients is not listed in any
      of the available DOAC investigating trials and registries, thus it is unclear if
      nonagenarians were included. Additionally, we could not find any subgroup
      analysis addressing this issue. There is an urgent need to collect more
      information on the safety and efficacy of oral anticoagulants in nonagenarians,
      especially regarding the role of DOACs, which are increasingly prescribed to this
      group of patients despite the lack of data. The best solution to this problem
      would be a prospective, randomized trial in this group of patients, however that
      would require a large investment of time, effort, and funds. In the meantime, we
      suggest subgroup analyses addressing the effects and safety of VKAs versus DOACs
      in nonagenarians, in case they have been included in previously completed or
      ongoing trials or registries. This could be feasible and would be desirable in
      view of the large amount of data already accumulated. Irrespective of age, anemia
      in patients receiving DOACs should be carefully investigated to rule out occult
      blood loss. With their known interaction profile and the possibility of
      monitoring these drugs, VKAs should be favored over DOACs in nonagenarians until
      more data are available regarding the safety of DOACs. 

PMID- 27038065
TI  - Examination and Estimation of Anticholinergic Burden: Current Trends and
      Implications for Future Research.
AB  - It is postulated that minimizing anticholinergic burden in older people may
      result in improved short-term memory and behavior, reduced confusion and
      delirium, and enhanced quality of life and daily functioning. The purpose of this
      opinion article was to investigate the current trends and future implications
      relating to the examination and estimation of anticholinergic burden in older
      people. Current evidence linking medicines with anticholinergic activity and
      cognitive impairment is derived mostly from observational data. Further research
      with larger trials or cohort studies with adequate power and appropriate follow
      up periods is required to confirm associations between anticholinergic burden and
      adverse outcomes. This article provides insights into different approaches for
      the estimation of anticholinergic burden. Network-based systems pharmacology
      models could be an effective way of understanding anticholinergic drug-induced
      adverse effects. The emphasis on mechanistic models may open new opportunities
      for researchers to understand adverse drug effects in clinical practice. In the
      interim, medicines with high anticholinergic activity should be avoided in older
      people, unless considered clinically essential. In this instance, they should be
      used at a low/titrated dose and for the shortest duration possible. It is
      therefore important to reinforce the clinical significance of reviewing
      anticholinergic medicines in older people. 

PMID- 27038066
TI  - A Probability Analysis of Historical Pregnancy and Fetal Data from Dutch Belted
      and New Zealand White Rabbit Strains from Embryo-Fetal Development Studies.
AB  - Embryo-fetal development (EFD) studies, typically in pregnant rats and rabbits,
      are conducted prior to enrolling females of reproductive age in clinical trials.
      Common rabbit strains used are the New Zealand White (NZW) and Dutch Belted (DB).
      As fetal abnormalities can occur in all groups, including controls, Historical
      Control Data (HCD) is compiled using data from control groups of EFD studies, and
      is used along with each study's concurrent control group to help determine
      whether fetal abnormalities are caused by the test article or are part of
      background incidences. A probability analysis was conducted on 2014 HCD collected
      at Charles River Inc., Horsham PA on Covance NZW, Covance DB, and Charles River
      (CR) NZW rabbits. The analysis was designed to determine the probability of 2 or
      3 out of a group of 22 does aborting their litter or of having a fetal
      abnormality by chance. Results demonstrate that pregnancy parameters and fetal
      observations differ not only between strains, but between sources of rabbits of
      the same strain. As a result the probability of these observations occurring by
      chance in two or three litters was drastically different. Although no one single
      strain is perfect, this analysis highlights the need to appreciate the inherent
      differences in pregnancy and fetal abnormalities between strains, and points out
      that an apparent isolated increased incidence of an observation in one strain
      will not necessarily be test-article related in another strain. A robust HCD is
      critical for interpretation of EFD rabbit studies, regardless of the rabbit
      strain used. 

PMID- 27038067
TI  - Chemical Diversity and Antimicrobial Activity of Salvia multicaulis Vahl
      Essential Oils.
AB  - The chemical compositions and antimicrobial activities of the essential oils
      (EOs) of aerial parts of Salvia multicaulis Vahl, collected during the same week
      from two different Lebanese regions, were investigated. The EOs were obtained by
      hydrodistillation using a Clevenger-type apparatus and characterized by GC and
      GC/MS analyses. The minimum inhibitory concentrations of these EOs were
      determined against one Gram-negative and two Gram-positive bacteria, one yeast,
      and five dermatophytes using the broth microdilution technique. One EO was
      notably active against Staphylococcus aureus, methicillin-resistant S. aureus,
      and all of the Trichophyton species tested. Nerolidol was found to be the major
      compound in the active oil; nerolidol was also absent from the inactive oil. This
      study demonstrated that nerolidol shows antimicrobial activity and therefore
      significantly contributes to the antimicrobial potential of the oil. The chemical
      diversity of worldwide S. multicaulis EOs was analyzed, revealing that the EOs of
      this study belong to two different chemotypes found in the literature. The
      nerolidol chemotype appears to be restricted to Lebanon, and it can be used as
      antimicrobial agent against external bacterial and fungal infections. 

PMID- 27038068
TI  - Exploring Cooperative Effects in Oxidative NHC Catalysis: Regioselective
      Acylation of Carbohydrates.
AB  - The utility of oxidative NHC catalysis for both the regioselective and
      chemoselective functionalization of carbohydrates is explored. Chiral NHCs allow
      for the highly regioselective oxidative esterification of various carbohydrates
      using aldehydes as acylation precursors. The transformation was also shown to be
      amenable to both cis/trans diol isomers, free amino groups, and selective for
      specific sugar epimers in competition experiments. Efficiency and
      regioselectivity of the acylation can be improved upon using two different NHC
      catalysts that act cooperatively. The potential of the method is documented by
      the regioselective acylation of an amino-linked neodisaccharide. 

PMID- 27038069
TI  - Through a glass darkly - ultrasound imaging in obstetric anaesthesia.

PMID- 27038070
TI  - Mechanism investigation for poloxamer 188 raw material variation in cell culture.
AB  - Variability in poloxamer 188 (P188) raw material, which is routinely used in cell
      culture media to protect cells from hydrodynamic forces, plays an important role
      in the process performance. Even though tremendous efforts have been spent to
      understand the mechanism of poloxamer's protection, the root cause for lot-to-lot
      variation was not clear. A recent study reported that the low performance was not
      due to toxicity but inefficiency to protect cells (Peng et al., Biotechnol Prog.
      2014;30:1411-1418). In this study, it was demonstrated for the first time that
      the addition of other surfactants even at a very low level can interfere with
      P188 resulting in a loss of efficiency. It was also found that the performance of
      P188 lots correlated well with its foam stability. Foam generated from low
      performing lots in baffled shaker flask lasts longer, which suggests that the
      components in the foam layers are different. The spiking of foam generated from a
      low performing lot into the media containing a high performance lot resulted in
      cell damage and low growth. Analytical studies using size exclusion
      chromatography (SEC) identified differences in high molecular weight (HMW)
      species present in the P188 lots. These differences are much clearer when
      comparing the HMW region of the SEC chromatogram of foam vs. bulk liquid samples.
      This study shows that low performing lots have enriched HMW species in foam
      samples due to high hydrophobicity, which can be potentially used as a screening
      assay. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog.,
      32:767-775, 2016.

PMID- 27038071
TI  - The Use of Qualitative Methods in Developing Implementation Strategies in
      Prevention Research for Stroke Survivors in Nigeria.
AB  - Implementing complex clinical interventions is a key challenge in many global
      regions. Local communities play a necessary role in enhancing feasibility and
      strengthening adaptive issues in the design and implementation of stroke
      interventions in developing countries. Drawing on the knowledge of physicians,
      patients, and caregivers, the authors employed qualitative methods as a phase 1
      strategy to explore the challenges of stroke management and improve the
      adaptability and efficient delivery of a multimodal preventive intervention for
      secondary stroke disease in Nigeria. A total of 22 individual interviews were
      conducted with healthcare professionals, as well as 12 focus groups with patients
      and caregivers. Findings revealed four operational domains to improve strategies
      for phase 2 implementation and intervention: (1) barriers influencing optimal
      adherence in stroke survivors, (2) patient health beliefs and perceptions of
      patient health beliefs by others, (3) adoption of the "patient report card," and
      (4) "medical action plan" and family management strategies.

PMID- 27038072
TI  - COMPARISON OF COMPUTED TOMOGRAPHY AND ABDOMINAL RADIOGRAPHY FOR DETECTION OF
      CANINE MECHANICAL INTESTINAL OBSTRUCTION.
AB  - Vomiting, often caused by mechanical intestinal obstruction, is common in dogs.
      Equivocal radiographic signs often necessitate repeat radiographs or additional
      imaging procedures. For our prospective, case-controlled, accuracy study, we
      hypothesized the following: (1) using computed tomography (CT), radiologists will
      be more sensitive and specific for detecting mechanical intestinal obstruction
      and recommending surgery compared to using radiographs; and (2) using
      measurements, radiologists will be more sensitive and specific using radiographs
      or CT for detecting mechanical intestinal obstruction and recommending surgery.
      Twenty dogs had abdominal radiographs and abdominal CT. Seventeen dogs had
      abdominal surgery and three dogs were not obstructed based on clinical follow-up.
      Confidence levels (five-point scale) of three experienced radiologists for
      mechanical intestinal obstruction and recommending surgery were recorded before
      and after making selected measurements. Eight dogs had surgically confirmed
      mechanical intestinal obstruction, and 12 dogs did not have obstruction. For
      detecting mechanical intestinal obstruction, CT was more sensitive (95.8% vs.
      79.2%) and specific (80.6% vs. 69.4%) compared to radiographs, but the difference
      was not statistically significant. For recommending surgery, radiography was more
      sensitive (91.7% vs. 83.3%) and specific (83.3% vs. 72.2%) than using CT, but
      differences were not statistically significant. We reported objective CT
      measurements for predicting small mechanical intestinal obstruction. By
      incorporating these objective data, the diagnosis of mechanical intestinal
      obstruction changed in five of 120 instances (radiographs and CT). In no instance
      (0/120), did the objective data change the recommendation for surgery. Using CT
      or abdominal radiographs for the detection of canine mechanical intestinal
      obstruction is sensitive and specific when evaluated by experienced veterinary
      radiologists. 

PMID- 27038073
TI  - DNA Origami Seesaws as Comparative Binding Assay.
AB  - The application of commonly used force spectroscopy in biological systems is
      often limited by the need for an invasive tether connecting the molecules of
      interest to a bead or cantilever tip. Here we present a DNA origami-based
      prototype in a comparative binding assay. It has the advantage of in situ readout
      without any physical connection to the macroscopic world. The seesaw-like
      structure has a lever that is able to move freely relative to its base. Binding
      partners on each side force the structure into discrete and distinguishable
      conformations. Model experiments with competing DNA hybridisation reactions
      yielded a drastic shift towards the conformation with the stronger binding
      interaction. With reference DNA duplexes of tuneable length on one side, this
      device can be used to measure ligand interactions in comparative assays.

PMID- 27038074
TI  - Inclusion and exclusion criteria in phase III trials with systemic agents in
      psoriasis: the external validity of drug development.

PMID- 27038075
TI  - Lactation and suckling behavior in the Iberian lynx.
AB  - Understanding the behavior of endangered species is crucial to improve the
      management tools to breed animals in captivity and, thus, to increase the success
      of ex situ conservation programs. In this study, we monitored suckling behavior
      of 26 cubs born between 2008 and 2012 at "El Acebuche" Iberian Lynx Breeding
      Centre. The cubs devoted 251 +/- 19.7 min (mean +/- SE) to lactation on the day
      of birth, while mothers spent 426 +/- 27 min (mean +/- SE) nursing their
      offspring. The time cubs spent suckling decreased exponentially as they grown,
      until they were fully weaned at 65 +/- 2.6 days. The onset of weaning (first
      intake of solid food) occurred at 54 +/- 1.35 days (mean +/- SE). Thus, the
      strict lactation period occupied most of the overall lactation period. Both
      suckling and maternal behavior were affected by litter size. In twins and
      triplets, the competition between siblings caused a decrease in the time spent
      suckling, in spite of the mothers spending more time nursing their young.
      Finally, no significant differences were found in time spent suckling between
      littermates or depending on the sex of the cub. Lactation appeared to play a key
      role in the nutrition of the Iberian lynx and should therefore be conveniently
      managed in captive breeding programs of this threatened species. Zoo Biol. 35:216
      221, 2016. (c) 2016 Wiley Periodicals, Inc. 

PMID- 27038076
TI  - Optimization of the thrombin generation test components to measure potency of
      factor VIII concentrates.
AB  - INTRODUCTION: The thrombin generation test (TGT) is used both as a global
      haemostasis assay, and to compare activities of coagulation factor concentrates
      that have been spiked into patient plasma. However, TGT has not been
      systematically optimized to evaluate factor VIII (FVIII) product potency. AIMS:
      To improve the sensitivity of TGT to FVIII and allow a comparative analysis of
      the thrombin generating capacities of FVIII concentrates against reference
      preparations with known FVIII activity. METHODS: Concentrations of TGT components
      (analytical variables) were assessed to maximize the linearity and range of
      responses to the concentration of FVIII. RESULTS: We optimized the range and
      sensitivity of the TGT assay with respect to FVIII through the addition of FXIa
      to the assay. Other parameters that were adjusted, i.e. tissue factor (TF),
      procoagulant lipids and plasma concentrations, did not improve the ability of the
      assay to measure both high and very low levels of FVIII. In the optimized TF/FXIa
      activated TGT assay, all thrombin generation curve parameters were suitable for
      FVIII quantification, but thrombin peak height and maximal velocity demonstrated
      better linearity in the desired FVIII range. We found that the optimized TF/FXIa
      activated TGT has a wider range of sensitivity to FVIII than a commercially
      available TGT. Additionally, we demonstrated that the TF/FXIa-activated assay
      performs adequately by comparing potency measurements of five commercially
      available FVIII products using TGT and traditional chromogenic and one-stage
      clotting assays. CONCLUSIONS: The optimized TGT assay can be used to quantify and
      compare the thrombin generating capacities of FVIII concentrates.

PMID- 27038077
TI  - Identification of the Burkholderia pseudomallei bacteriophage ST79 lysis gene
      cassette.
AB  - AIMS: To identify and characterize the lysis gene cassette from the bacteriophage
      ST79 that lyses Burkholderia pseudomallei. METHODS AND RESULTS: Approximately 1.5
      kb of ST79 lysis genes were identified from the phage genome data. It was
      composed of holin, peptidase M15A or endolysin, lysB and lysC. Each gene and its
      combinations were cloned into Escherichia coli and the lytic effects were
      measured. Co-expression of holin and peptidase M15A showed the highest lysis
      activity. Expression of holin, lysB/C or holin-peptidase M15A-lysB/lysC lysed the
      E. coli membrane, whereas peptidase M15A alone did not. The predicted
      transmembrane structures of holin and lysB/C indicated that they could be
      inserted into the bacterial membrane to form pores, affecting cell permeability
      and causing lysis. CONCLUSION: This is the first report of an investigation into
      the lysis genes of B. pseudomallei's lytic phage using E. coli as a model.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Burkholderia pseudomallei, a Gram-negative
      bacterium causing an infectious disease, is intrinsically resistant to several
      antibiotics, and a vaccine is not available. The lysis genes of ST79, the first
      reported lytic bacteriophage of B. pseudomallei, were characterized. The
      development of ST79 as an alternative treatment for skin ulceration, for example,
      or to be used as a gene cloning tool for B. pseudomallei may be possible with
      this knowledge.

PMID- 27038078
TI  - Synergistic influence of topomimetic and chondroitin sulfate-based treatments on
      osteogenic potential of Ti-6Al-4V.
AB  - We combined topographical and chemical surface modifications of Ti-6Al-4V (TA6V)
      to improve its osteogenic potential. By acid-etching, we first generated
      topomimetic surface features resembling, in size and roughness, bone cavities
      left by osteoclasts. Next, we coated these surfaces with biomimetic Layer-by
      Layer films (LbL), composed of chondroitin sulfate A and poly-l-lysine that were
      mechanically tuned after a post-treatment with genipin. The structural impact of
      each surface processing step was thoroughly inspected. The desired
      nano/microrough topographies of TA6V were maintained upon LbL deposition. Whereas
      no significant promotion of adhesion and proliferation of MC3T3-E1 preosteoblasts
      were detected after independent or combined modifications of the topography and
      the chemical composition of the substrates, osteogenic maturation was promoted
      when both surface treatments were combined, as was evidenced by significant long
      term matrix mineralization. The results open promising route toward improved
      osseointegration of titanium-based implants. (c) 2016 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 104A: 1988-2000, 2016.

PMID- 27038079
TI  - A comparative study of socio-demographic and substance use correlates in early
      onset psychosis.
AB  - BACKGROUND: Comorbid substance use, particularly cannabis among adolescents with
      mental illness, is a major public health concern in developing countries with
      limited mental health resources. Better understanding of the association between
      cannabis use and other polysubstance use and early mental illness will provide
      for more targeted early interventions. AIM: This aim of this study was to examine
      the socio-demographic profile and cannabis use characteristics among adolescents
      with first-episode early-onset psychosis (EOP) and compare with age-matched and
      gender-matched adolescents with first-episode non-psychotic mental illness
      (controls). METHOD: Forty-five adolescents with first-episode EOP and 45 controls
      were assessed using a clinical interview, Positive and Negative Syndrome Scale
      and World Health Organization Alcohol, Smoking and Substance Involvement
      Screening test (ASSIST) for substance-related problems. RESULTS: There were
      significant socio-demographic differences among the adolescents with EOP (73%
      Black, 64% from low family income, 44% from rural areas) compared with controls
      (24% Black, 53% from low family income, 2% from rural areas). Although there was
      no difference in lifetime cannabis use, EOP adolescents differed in motivation
      for cannabis use, had increased current cannabis use (38%, P = 0.01) and more
      frequent use (52%, P = 0.04) compared with controls (16% current and 18% frequent
      use). EOP adolescents reported more hazardous use with higher ASSIST mean
      cannabis-specific involvement scores (EOP 10,2; controls 2,3; P = 0.004).
      CONCLUSION: The differences in socio-demographic variables may reflect the marked
      disparity in access to mental health care for rural Black youth. Psychotic youth
      may be more vulnerable to comorbid cannabis-related problems than other mentally
      ill adolescents. The study highlights the need for early introduction of
      substance use interventions among adolescents with mental illness.

PMID- 27038080
TI  - Surface shapes and surrounding environment analysis of single- and double
      stranded DNA-binding proteins in protein-DNA interface.
AB  - Protein-DNA bindings are critical to many biological processes. However, the
      structural mechanisms underlying these interactions are not fully understood.
      Here, we analyzed the residues shape (peak, flat, or valley) and the surrounding
      environment of double-stranded DNA-binding proteins (DSBs) and single-stranded
      DNA-binding proteins (SSBs) in protein-DNA interfaces. In the results, we found
      that the interface shapes, hydrogen bonds, and the surrounding environment
      present significant differences between the two kinds of proteins. Built on the
      investigation results, we constructed a random forest (RF) classifier to
      distinguish DSBs and SSBs with satisfying performance. In conclusion, we present
      a novel methodology to characterize protein interfaces, which will deepen our
      understanding of the specificity of proteins binding to ssDNA (single-stranded
      DNA) or dsDNA (double-stranded DNA). Proteins 2016; 84:979-989. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27038081
TI  - Nursing students' experiences of ethical issues in clinical practice: A New
      Zealand study.
AB  - Nursing students experience ethical problems in clinical practice in a different
      way from registered nurses. In order to develop ethical reasoning and competence
      in nursing students, nurse educators must recognise the unique issues students
      face. This research described the occurrence of ethical issues in clinical
      practice for 373 undergraduate nursing students who responded to a national
      questionnaire investigating the frequency of pre-determined ethical issues and
      the corresponding level of distress. Over two thirds of respondents experienced
      breaches of a patient's right to confidentiality, privacy, dignity or respect and
      87% experienced unsafe working conditions. The most distressing issues were those
      that compromised patient safety, including unsafe healthcare practices, working
      conditions and suspected abuse or neglect. Themes that emerged from an open-ended
      question included lack of support and supervision, bullying and end of life
      issues. This research found the frequency at which ethical issues are experienced
      was highest in year three participants. However, the overall distress levels were
      lower for the majority of issues for those participants in the later part of
      their degree. Recommendations from this research include developing ethics
      education around the main concerns that students face in order to enhance
      students' understanding, resilience and ability to respond appropriately.

PMID- 27038082
TI  - Preceptors' experiences of using a competence assessment tool to assess
      undergraduate nursing students.
AB  - The purpose of this study was to explore Irish preceptors' experience of using a
      competence tool to assess undergraduate nursing students' clinical competence.
      This study used a mixed methods design. This study was conducted in two phases,
      the qualitative phase involved six focus group interviews to ascertain
      preceptors' experiences of using an assessment tool to assess clinical
      competence. The quantitative phase involved a descriptive survey measuring
      preceptors (N = 843) attitudes linked with the use of the assessment tool. The
      key themes that emerged from qualitative analysis were challenges of using the
      assessment tool, recognising competence and valuing adult learners. The
      challenges of using the tool included negotiating complex language and time
      constraints in completing assessments. Recognising competence revealed the use of
      intuition and subjectivity. While valuing adult learners acknowledged the
      reciprocal learning process between the preceptor and the learner. These findings
      reveal the inherent skills of preceptors to intuitively and subjectively
      recognise competence. The quantitative findings revealed merits and challenges
      for the preceptors using the assessment tool. In particular the complexity of the
      language was highlighted as an issue. A key recommendation from this research is
      the need to revise the assessment tool to support objective and subjective
      measurement of competence. 

PMID- 27038083
TI  - Preparing health students for interprofessional placements.
AB  - Clinical education increasingly includes opportunities for interprofessional (IP)
      placements but few opportunities for students and supervisors to adequately
      prepare for such placements. The aim of this project was to further develop and
      evaluate an online multidisciplinary resource that was originally designed to
      prepare students for single-discipline placements. The revised resource aimed to
      prepare health students and their supervisors for IP placements. The resource was
      trialled in host organisations with participants from naturopathy, nursing,
      osteopathy and pharmacy. The resource used language that was common to all
      participants and comprised activities that had broad relevance such as
      orientating students to specific placements, developing learning plans,
      clarifying roles, rights and responsibilities, and clinical scenarios that raised
      ethical and professional issues. The effectiveness of the resource as an IP
      learning tool was evaluated using an E-survey, focus groups and feedback from the
      project team. According to participants, the resource afforded insights into what
      other disciplines do and opportunities for cross-disciplinary interactions, which
      helped break down stereotypes and misconceptions. Cross-disciplinary
      commonalities such as those pertaining to patient care, communication and ethics
      became evident. Collaborative projects involving academics, clinical supervisors
      and students from multiple disciplines provided an opportunity for culture change
      in an education organisation from single discipline to a more collaborative
      interdisciplinary one. 

PMID- 27038084
TI  - Students' perceptions of digital narratives of compassionate care.
AB  - This study set out to explore the learning that occurred from listening to
      narratives of compassionate care, and to identify students' preferred story
      formats and other potential uses of such stories. Four short stories in different
      media formats were used. Data was gathered from an evaluation questionnaire and
      thematic analysis undertaken; this generated two themes: 'Learning from the
      stories' and 'Students perceptions of the value of different media formats and
      other potential uses'. Sub-themes related to the narratives themselves emerged
      from first theme these included: person-centredness, compassion, relatives,
      effective mentor support and 'the world of the student nurse'. There was evidence
      of the stories acting as a trigger for reflection and discussion although
      sometimes, cognitive dissonance arose. Audiofiles suitable for use as podcasts,
      with and without music, and digital stories all proved to be effective digital
      narratives for this type of learning activity. Students suggested such stories
      would be also useful for preparing them for practice placements and training of
      mentors. In conclusion, digital narratives can promote effective reflective
      thinking and discussion about compassionate care. The findings support many
      aspects of narrative pedagogy previously reported but add to this by providing
      insight into student nurses' learning from peer experiences. 

PMID- 27038085
TI  - Virtual patient simulation in psychiatric care - A pilot study of digital support
      for collaborate learning.
AB  - Psychiatric and mental health nursing is built on a trusted nurse and patient
      relationship. Therefore communication and clinical reasoning are two important
      issues. Our experiences as teachers in psychiatric educational programmes are
      that the students feel anxiety and fear before they start their clinical
      practices in psychiatry. Therefore there is a need for bridging over the fear.
      Technology enhanced learning might support such activities so we used Virtual
      patients (VPs), an interactive computer simulations of real-life clinical
      scenarios. The aim of this study was to investigate 4th term nursing students'
      opinions on the use of Virtual Patients for assessment in a Mental Health and Ill
      health course module. We asked 24 volunteering students to practise with five
      different VP cases during almost 10 weeks before the exam. The participants were
      gathered together for participating in a written and an oral evaluation. The
      students were positive to the use of VPs in psychiatry and were very positive to
      use VPs in their continued nursing education. It seems that Virtual Patients can
      be an activity producing pedagogic model promoting students' independent
      knowledge development, critical thinking, reflection and problem solving ability
      for nurse students in psychiatric care. 

PMID- 27038086
TI  - The effect of preceptor role effectiveness on newly licensed registered nurses'
      perceived psychological empowerment and professional autonomy.
AB  - The first year turnover rate for newly licensed registered nurses is roughly 30%
      and increases to about 57% in the second year (Twibell et al., 2012). An
      effective preceptorship has been shown to better facilitate the first year
      transition (Hodges et al., 2008) and increase retention rates (Pine and Tart,
      2007). The purpose of this study was to examine the relationships between newly
      licensed registered nurses' perceived preceptor role effectiveness, psychological
      empowerment and professional autonomy. A prospective, cross-sectional,
      descriptive research design was used. Sixty-nine newly licensed registered nurses
      were recruited and surveyed. Newly licensed registered nurses were found to have
      moderately high levels of perceived preceptor role effectiveness, psychological
      empowerment, and professional autonomy. Preceptor role effectiveness had
      significant, moderately, positive relationships with professional autonomy and
      psychological empowerment. There was also a significant relationship found
      between professional autonomy and psychological empowerment. Results show that
      preceptor role effectiveness is linked to increased professional autonomy and
      psychological empowerment. Therefore, effective preceptorships are necessary in
      easing the newly licensed registered nurse's transition to practice. Strategies
      to ensure effective preceptorships and enhance the NRLN's transition to practice
      are proposed.

PMID- 27038087
TI  - Learning about population-health through a community practice learning project:
      An evaluation study.
AB  - Increasing student nurse numbers requiring community placement learning
      opportunities has led to insufficient numbers of community nurses being available
      to support student nurses in the community. Although the study presented in the
      article is based in the UK this issue is reported widely in the literature across
      the globe. Universities in many countries have had to find innovative ways of
      providing community health learning opportunities for student nurses. This
      article reports on how one university in the UK has approached this challenge
      through students engaging in a population-based study in the community through
      group work. A research study was undertaken into this innovation which found that
      the student nurses engaged well with the project and with their groups and
      undertaking the project had positive value and impact on them and their
      understanding of population-health. Issues that arose for them largely focused on
      unequal participation in the group work by some with many participants perceiving
      that they had done more work on the group project and presentation than others in
      their group. However, working in this way was perceived to be a good learning
      experience for the majority of participants. 

PMID- 27038088
TI  - Perceived barriers to the professional development of modern nursing in Italy - A
      discussion paper.
AB  - The aim of this paper is to discuss the development of modern nursing in Italy.
      Specifically, the paper aims to draw attention to the fact that while nursing in
      Italy has mirrored developments in Europe, in many respects the advancement of
      the profession is much less accelerated. The paper considers the reasons for this
      and the contributing factors and explores possible solutions. 

PMID- 27038089
TI  - Eruption of urticaria and angioedema induced by binging and purging in an
      anorexia nervosa patient.
AB  - BACKGROUND: Anorexia nervosa is a perplexing psycho-biological disorder with a
      systemic nature, which can present in almost every organ and system of the body.
      Among the different presentations of starvation, several immunological and
      dermatological manifestations have been documented. To the best of our knowledge
      the occurrence of urticaria and angioedema in patients with binge or purge
      behaviors has yet to be documented. CASE PRESENTATION: We present a 16-year-old
      female patient diagnosed with anorexia nervosa binge/purge type, who presented
      with urticaria and angioedema shortly after binge/purge episodes that subsided
      when these behaviors ceased. Other possible causes for the urticaria were ruled
      out. DISCUSSION: This finding may represent a form of inducible urticaria,
      exacerbated in low-weight patients by the occurrence of binge/purge behaviors. We
      wish to report this observation in an attempt to widen the scope of the physical
      signs that may accompany eating disorders and bring this specific phenomenon into
      awareness. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:822-825).

PMID- 27038090
TI  - A loss-of-function allele of OsHMA3 associated with high cadmium accumulation in
      shoots and grain of Japonica rice cultivars.
AB  - Excessive cadmium (Cd) accumulation in rice poses a risk to food safety. OsHMA3
      plays an important role in restricting Cd translocation from roots to shoots. A
      non-functional allele of OsHMA3 has been reported in some Indica rice cultivars
      with high Cd accumulation, but it is not known if OsHMA3 allelic variation is
      associated with Cd accumulation in Japonica cultivars. In this study, we
      identified a Japonica cultivar with consistently high Cd accumulation in shoots
      and grain in both field and greenhouse experiments. The cultivar possesses an
      OsHMA3 allele with a predicted amino acid mutation at the 380(th) position from
      Ser to Arg. The haplotype had no Cd transport activity when the gene was
      expressed in yeast, and the allele did not complement a known nonfunctional
      allele of OsHMA3 in F1 test. The allele is present only in temperate Japonica
      cultivars among diversity panels of 1483 rice cultivars. Different cultivars
      possessing this allele showed greatly increased root-to-shoot Cd translocation
      and a shift in root Cd speciation from Cd-S to Cd-O bonding determined by
      synchrotron X-ray absorption spectroscopy. Our study has identified a new loss-of
      function allele of OsHMA3 in Japonica rice cultivars leading to high Cd
      accumulation in shoots and grain.

PMID- 27038092
TI  - Erratum to "Topical iontophoretic delivery of ionizable, biolabile aciclovir
      prodrugs: A rational approach to improve cutaneous bioavailability" [Eur. J.
      Pharm. Biopharm. 99 (2016) 103-113].

PMID- 27038093
TI  - Functionalization of Two-Dimensional MoS2 : On the Reaction Between MoS2 and
      Organic Thiols.
AB  - Two-dimensional layered transition metal dichalcogenides (TMDs) have attracted
      great interest owing to their unique properties and a wide array of potential
      applications. However, due to their inert nature, pristine TMDs are very
      challenging to functionalize. We demonstrate a general route to functionalize
      exfoliated 2H-MoS2 with cysteine. Critically, MoS2 was found to be facilitating
      the oxidation of the thiol cysteine to the disulfide cystine during
      functionalization. The resulting cystine was physisorbed on MoS2 rather than
      coordinated as a thiol (cysteine) filling S-vacancies in the 2H-MoS2 surface, as
      originally conceived. These observations were found to be true for other organic
      thiols and indeed other TMDs. Our findings suggest that functionalization of two
      dimensional MoS2 using organic thiols may not yield covalently or datively
      tethered functionalities, rather, in this instance, they yield physisorbed
      disulfides that are easily removed.

PMID- 27038091
TI  - Particulate delivery systems for vaccination against bioterrorism agents and
      emerging infectious pathogens.
AB  - Bioterrorism agents that can be easily transmitted with high mortality rates and
      cause debilitating diseases pose major threats to national security and public
      health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus
      outbreak in Brazil, now spreading throughout Latin America, are case examples of
      emerging infectious pathogens that have incited widespread fear and economic and
      social disruption on a global scale. Prophylactic vaccines would provide
      effective countermeasures against infectious pathogens and biological warfare
      agents. However, traditional approaches relying on attenuated or inactivated
      vaccines have been hampered by their unacceptable levels of reactogenicity and
      safety issues, whereas subunit antigen-based vaccines suffer from suboptimal
      immunogenicity and efficacy. In contrast, particulate vaccine delivery systems
      offer key advantages, including efficient and stable delivery of subunit
      antigens, co-delivery of adjuvant molecules to bolster immune responses, low
      reactogenicity due to the use of biocompatible biomaterials, and robust
      efficiency to elicit humoral and cellular immunity in systemic and mucosal
      tissues. Thus, vaccine nanoparticles and microparticles are promising platforms
      for clinical development of biodefense vaccines. In this review, we summarize the
      current status of research efforts to develop particulate vaccine delivery
      systems against bioterrorism agents and emerging infectious pathogens. WIREs
      Nanomed Nanobiotechnol 2017, 9:e1403. doi: 10.1002/wnan.1403 For further
      resources related to this article, please visit the WIREs website.

PMID- 27038094
TI  - Redoubling the ring size of an endomorphin-2 analog transforms a centrally acting
      mu-opioid receptor agonist into a pure peripheral analgesic.
AB  - The study reports the synthesis and biological evaluation of two opioid analogs,
      a monomer and a dimer, obtained as products of the solid-phase, side-chain to
      side-chain cyclization of the pentapeptide Tyr-d-Lys-Phe-Phe-AspNH2 . The binding
      affinities to the mu, delta, and kappa opioid receptors, as well as results
      obtained in a calcium mobilization functional assay are reported. Tyr-[d-Lys-Phe
      Phe-Asp]2 -NH2 1 was a potent and selective full agonist of mu with sub-nanomolar
      affinity, while the dimer (Tyr-[d-Lys-Phe-Phe-Asp]2 -NH2 )2 2 showed a
      significant mixed mu/kappa affinity, acting as an agonist at the mu. Molecular
      docking computations were utilized to explain the ability of the dimeric
      cyclopeptide 2 to interact with the receptor. Interestingly, in spite of the
      increased ring size, the higher flexibility allowed 2 to fold and fit into the mu
      receptor binding pocket. Both cyclopeptides were shown to elicit strong
      antinociceptive activity after intraventricular injection but only cyclomonomer 1
      was able to cross the blood-brain barrier. However, the cyclodimer 2 displayed a
      potent peripheral antinociceptive activity in a mouse model of visceral
      inflammatory pain. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106:
      309-317, 2016. 

PMID- 27038095
TI  - Distinguishing Mediational Models and Analyses in Clinical Psychology: Atemporal
      Associations Do Not Imply Causation.
AB  - PURPOSE: A popular way to attempt to discern causality in clinical psychology is
      through mediation analysis. However, mediation analysis is sometimes applied to
      research questions in clinical psychology when inferring causality is impossible.
      This practice may soon increase with new, readily available, and easy-to-use
      statistical advances. Thus, we here provide a heuristic to remind clinical
      psychological scientists of the assumptions of mediation analyses. APPROACH: We
      describe recent statistical advances and unpack assumptions of causality in
      mediation, underscoring the importance of time in understanding mediational
      hypotheses and analyses in clinical psychology. Example analyses demonstrate that
      statistical mediation can occur despite theoretical mediation being improbable.
      CONCLUSION: We propose a delineation of mediational effects derived from cross
      sectional designs into the terms temporal and atemporal associations to emphasize
      time in conceptualizing process models in clinical psychology. The general
      implications for mediational hypotheses and the temporal frameworks from within
      which they may be drawn are discussed.

PMID- 27038096
TI  - Violent offenders as a target population for Public Mental Health Care.
AB  - The study sought to specify which part of a population of young adult violent
      offenders in Amsterdam (mean age 24.9 years, sd = 8.2) were eligible for Public
      Mental Health Care (PMHC). The results of a semi-structured clinical interview
      were used (N = 454), which included the Self-Sufficiency Matrix (SSM-D). Using
      the SSM-D and two distinct definitions of what constitutes a need for PMHC, the
      size of the PMHC target population was determined twice. Depending on which
      definition was used, 35.9% (mathematical algorithm which put weights to single
      SSM-D domains) and 34.8% (problematic levels of self-sufficiency on a selection
      of domains) appeared to be eligible for entering the PMHC system. The study
      confirms that a substantial proportion of vulnerable people are among the
      forensic population. 

PMID- 27038097
TI  - Live high, train low - influence on resting and post-exercise hepcidin levels.
AB  - The post-exercise hepcidin response during prolonged (>2 weeks) hypoxic exposure
      is not well understood. We compared plasma hepcidin levels 3 h after exercise [6
      * 1000 m at 90% of maximal aerobic running velocity (vVO2max )] performed in
      normoxia and normobaric hypoxia (3000 m simulate altitude) 1 week before, and
      during 14 days of normobaric hypoxia [196.2 +/- 25.6 h (median: 200.8 h; range:
      154.3-234.8 h) at 3000 m simulated altitude] in 10 well-trained distance runners
      (six males, four females). Venous blood was also analyzed for hepcidin after 2
      days of normobaric hypoxia. Hemoglobin mass (Hbmass ) was measured via CO
      rebreathing 1 week before and after 14 days of hypoxia. Hepcidin was suppressed
      after 2 (Cohen's d = -2.3, 95% confidence interval: [-2.9, -1.6]) and 14 days of
      normobaric hypoxia (d = -1.6 [-2.6, -0.6]). Hepcidin increased from baseline, 3 h
      post-exercise in normoxia (d = 0.8 [0.2, 1.3]) and hypoxia (d = 0.6 [0.3, 1.0]),
      both before and after exposure (normoxia: d = 0.7 [0.3, 1.2]; hypoxia: d = 1.3
      [0.4, 2.3]). In conclusion, 2 weeks of normobaric hypoxia suppressed resting
      hepcidin levels, but did not alter the post-exercise response in either normoxia
      or hypoxia, compared with the pre-exposure response.

PMID- 27038098
TI  - Impact of perampanel on pharmacokinetics of concomitant antiepileptics in
      patients with partial-onset seizures: pooled analysis of clinical trials.
AB  - AIMS: To evaluate the impact of perampanel and demographics on clearance of
      concomitant antiepileptic drugs (AEDs), in patients with refractory partial-onset
      seizures. METHODS: Pooled data from three Phase III clinical studies with
      adjunctive perampanel were used. Blood samples for evaluation of 11 concomitant
      AEDs were taken during baseline (before perampanel initiation), and at weeks 10,
      14, and 19 during the maintenance phase of perampanel treatment (2-12 mg/day,
      once daily at bedtime). Models estimating apparent clearance of each concomitant
      AED were fitted to the data, and the effects of perampanel and demographic
      variables on clearance were determined. Final models were assessed with goodness
      of fit plots including population predictions and individual predictions against
      observations. RESULTS: No significant impact of perampanel on clearance was found
      for clonazepam (n = 81), levetiracetam (n = 330), phenobarbital (n = 54),
      phenytoin (n = 90), topiramate (n = 226) or zonisamide (n = 93). Statistically
      significant, but small and not clinically relevant increases in model-predicted
      clearance were detected for carbamazepine (+4.3% with 12 mg perampanel; n = 379),
      clobazam (+3.4% males, +7.7% females, 12 mg; n = 114), lamotrigine (+9.3%, 12 mg;
      n = 356), and valproic acid (+5.0%, 12 mg; n = 349). Oxcarbazepine clearance was
      reduced (26%; n = 200), but the clinical relevance is unclear as levels of the
      active metabolite (the monohydroxy derivative of oxcarbazepine) were not
      measured. CONCLUSIONS: Population PK data show that perampanel (2-12 mg/day, once
      daily at bedtime) has no relevant impact on the clearance of the most commonly
      used concomitant AEDs.

PMID- 27038099
TI  - Aortic annulus to left coronary distance as a predictor for persistent left
      bundle branch block after TAVI.
AB  - OBJECTIVES: To identify potential predictors for ventricular conduction delay and
      to evaluate the impact of interventricular dyssynchrony on mortality after
      implantation of a balloon-expandable aortic valve (BEV). METHODS AND RESULTS:
      Clinical, computertomographical (CT), and electrocardiographical (ECG) data from
      225 transcatheter aortic valve implantation (TAVI) patients were analyzed.
      Procedures were performed between May 2010 and September 2013 via transfemoral
      access using a BEV. Incidence of new-onset left bundle branch block (NOP-LBBB) at
      discharge was 23.1% (n = 52). Predictive factors for NOP-LBBB were first degree
      atrioventricular (AV) block (odds ratio (OR): 3.91, 95% confidence interval (CI):
      1.58 to 9.64), area cover index (OR: 1.83, 95% CI: 1.26 to 2.67), annulus
      calcification > first degree (OR: 3.01, 95% CI: 1.36 to 6.66), and annulus to
      left coronary distance (OR: 0.65, 95% CI: 0.44 to 0.96). At 1-year follow-up, no
      significant difference was observed concerning all-cause mortality (15.6% among
      non NOP-LBBB and 9.6% among NOP-LBBB patients, P = 0.278) and cardiovascular
      mortality (4.6% among non NOP-LBBB and 5.8% among NOP-LBBB patients, P = 0.737).
      CONCLUSION: In addition to previous predictors, annulus to left coronary distance
      and area cover index have been identified as new predictors for NOP-LBBB. NOP
      LBBB showed no relevant impact on mortality after one year. Further investigation
      including larger populations and longer follow-up is required to confirm these
      findings and develop an algorithm for identification of patients at risk for NOP
      LBBB associated adverse events. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038100
TI  - End-of-life care for hospitalized patients with metastatic melanoma in France: a
      nationwide, register-based study.
AB  - BACKGROUND: Although the aggressiveness of end-of-life cancer care has come under
      great scrutiny over the past two decades, little is known about the intensity of
      care and treatments in the last months of life of patients with metastatic
      melanoma. OBJECTIVES: To measure the prevalence of aggressive cancer care use,
      and to assess the frequency of palliative care referral over the course of the
      last 3 months of life of hospitalized patients who died from metastatic melanoma.
      METHODS: A nationwide register-based study in France was carried out, including
      all hospitalized adults aged >= 20 years who died from metastatic melanoma in
      metropolitan France between 2010 and 2013. RESULTS: Of 3889 patients who died
      from metastatic melanoma, 51.9% received chemotherapy in the last 3 months before
      death, 25.9% in the last month, 12.9% in the last 2 weeks and 7.6% in the last
      week. On average, patients were hospitalized for 31.7 days over the course of
      their last 3 months of life. During the final month before death, 12.0% of
      patients received radiation therapy, 14.0% received blood transfusion, 12.1% were
      transferred into an intensive care unit and 19.7% remained hospitalized
      continuously. Palliative care needs were identified in 78.4% of patients, with
      variations according to the type of facility. In total 17% of all patients died
      in palliative care inpatient units. CONCLUSIONS: Treatment intensity near the end
      of life of patients with metastatic melanoma raises concerns for the quality of
      care. There is a need for clinical guidelines and adequate support to facilitate
      patient-physician communication and to improve access to palliative care
      services.

PMID- 27038101
TI  - Antimicrobial efficiency of mouthrinses versus and in combination with different
      photodynamic therapies on periodontal pathogens in an experimental study.
AB  - BACKGROUND AND OBJECTIVE: In the therapy of destructive periodontal disease,
      chemical antimicrobial agents and increasingly photodynamic therapy (PDT) play an
      important adjunctive role to standard mechanical anti-infective treatment
      procedures. However, both antiseptic methods have their shortcomings in terms of
      eliminating periodontal pathogens. The aim of the study was to compare the
      antibacterial efficacy of different antiseptic mouthrinses, of a conventional and
      a new, modified PDTplus as well as of the different antiseptic mouthrinses
      combined with either the conventional or the modified PDTplus against
      periopathogens. MATERIAL AND METHODS: Six representative periodontitis-associated
      bacterial strains were grown for 24 h under anaerobic conditions. After mixing
      the individual cell pellets they were exposed to 10 different antiseptic
      mouthrinse formulations: chlorhexidine (0.2%, 0.06%, CHX); CHX + cetylpyridinium
      chloride (each 0.05%); sodium hypochlorite (0.05%); polyhexanide (0.04%, PHMB1;
      0.1%, PHMB2); octenidine dihydrochloride (0.1%); fluoride (250 ppm); essential
      oils; povidone iodine (10%); and saline (0.9%, NaCl) as control. Furthermore, the
      bacteria were treated with conventional PDT based on light-emitting diodes and a
      new modified photodisinfection combining photosensitizer with hydrogen peroxide
      to PDTplus also based on light-emitting diodes. In addition to the single
      treatments, a combined application of antiseptic exposure followed by use of PDT
      or PDTplus was performed. The microbial viability was characterized by analyzing
      colony growth and fluorescence-based vitality proportions. RESULTS: Nearly all
      mouthrinses caused a statistically significant growth inhibition. The most
      effective antiseptics, CHX (0.2%), CHX/cetylpyridinium chloride and octenidine
      dihydrochloride, inhibited bacterial growth completely. Conventional PDT resulted
      in moderate reduction of colony growth. The modified PDTplus achieved maximum
      antimicrobial effect. The combination of antiseptic exposure and PDT against
      periopathogens predominantly increased antibacterial efficacy compared to the
      single applications. The mouthrinse containing essential oil seemed to interfere
      with PDT. CONCLUSION: A combination therapy of preceding chemotherapeutical
      exposure and subsequent photodisinfection may be a more effective and promising
      antibacterial treatment than single applications of the antiseptic methods. The
      modified PDTplus using oxygen-enriched toluidine showed a superior antibacterial
      effect on periodontal pathogens to conventional PDT and to the majority of the
      investigated mouthrinses.

PMID- 27038102
TI  - Fine needle aspiration cytology diagnosis of a pancreatoblastoma in an infant:
      case report with a summary of prior published cases.

PMID- 27038104
TI  - Changing of the Guard.

PMID- 27038103
TI  - Dysregulated axonal RNA translation in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease that
      has been associated with a diverse array of genetic changes. Prominent among
      these are mutations in RNA-binding proteins (RBPs) or repeat expansions that give
      rise to toxic RNA species. RBPs are additionally central components of pathologic
      aggregates that constitute a disease hallmark, suggesting that dysregulation of
      RNA metabolism underlies disease progression. In the context of neuronal
      physiology, transport of RNAs and localized RNA translation in axons are
      fundamental to neuronal survival and function. Several lines of evidence suggest
      that axonal RNA translation is a central process perturbed by various pathogenic
      events associated with ALS. Dysregulated translation of specific RNA groups could
      underlie feedback effects that connect and reinforce disease manifestations.
      Among such candidates are RNAs encoding proteins involved in the regulation of
      microtubule dynamics. Further understanding of axonally dysregulated RNA targets
      and of the feedback mechanisms they induce could provide useful therapeutic
      insights. WIREs RNA 2016, 7:589-603. doi: 10.1002/wrna.1352 For further resources
      related to this article, please visit the WIREs website.

PMID- 27038105
TI  - Dark adaptation of M-cones in the retina.

PMID- 27038106
TI  - Is there sufficient evidence to claim muscle units are not localised and
      functionally grouped within the human gastrocnemius?

PMID- 27038107
TI  - Reply from J. S. Blouin, H. J. Brown, M. E. Heroux, J. T. Inglis and G. P.
      Siegmund.

PMID- 27038108
TI  - Corrigendum. Prolonged ischaemia impairs muscle blood flow and oxygen uptake
      dynamics during subsequent heavy exercise.

PMID- 27038109
TI  - The Angioedema Quality of Life Questionnaire (AE-QoL) - assessment of sensitivity
      to change and minimal clinically important difference.
AB  - BACKGROUND: The Angioedema Quality of Life Questionnaire (AE-QoL) has recently
      been developed and validated as the first specific patient-reported outcome tool
      to assess quality of life (QoL) impairment in recurrent angioedema patients. As
      of yet, its sensitivity to change and minimal clinically important difference
      (MCID) have not been established. METHODS: Recurrent angioedema patients with
      chronic spontaneous urticaria or hereditary angioedema were repeatedly asked to
      complete the AE-QoL along with the SF-12 and other anchors for QoL impairment and
      disease activity during routine care visits. The sensitivity to change of AE-QoL
      was determined by correlating changes in its scores over time with changes in the
      applied anchors. In addition, the MCID was determined using anchor-based and
      distributional criterion-based approaches. RESULTS: Two hundred and seventy-eight
      patients contributed data sets for analysis. Baseline AE-QoL values were found to
      correlate well with SF-12 results as well as all other applied anchors for
      angioedema-related QoL impairment and disease activity. In addition, AE-QoL score
      changes over time correlated significantly with changes in the above anchors,
      thus demonstrating its sensitivity to change. The MCID of the AE-QoL total score
      was found to be six points. CONCLUSION: The AE-QoL is a valuable tool to assess
      changes of QoL impairment in recurrent angioedema patients over time, including
      changes due to treatment.

PMID- 27038110
TI  - Absence of anti-HMG-CoA reductase autoantibodies in severe self-limited statin
      related myopathy.
AB  - INTRODUCTION: Patients with self-limited statin-related myopathy improve
      spontaneously when statins are stopped. In contrast, patients with statin
      associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl
      glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive
      therapy to control their disease. On initial presentation, it can sometimes be
      difficult to distinguish between these 2 diseases, as both present with muscle
      pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this
      study was to determine whether patients with severe self-limited statin-related
      myopathy also make anti-HMGCR autoantibodies. METHODS: We screened 101 subjects
      with severe self-limited cerivastatin-related myopathy for anti-HMGCR
      autoantibodies. RESULTS: No patient with severe self-limited cerivastatin-related
      myopathy had anti-HMGCR autoantibodies. CONCLUSION: Anti-HMGCR autoantibody
      testing can be used to help differentiate whether a patient has self-limited
      myopathy due to cerivastatin or autoimmune statin-associated myopathy; these
      findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016.

PMID- 27038111
TI  - Unexpected Roles for Ciliary Kinesins and Intraflagellar Transport Proteins.
AB  - Transport of proteins in the ciliary shaft is driven by microtubule-dependent
      motors, kinesins. Prior studies suggested that the heterotrimeric ciliary kinesin
      may be dispensable for certain aspects of transport in specialized cilia of
      vertebrate photoreceptor cells. To test this possibility further, we analyzed the
      mutant phenotype of the zebrafish kif3a gene, which encodes the common motor
      subunit of heterotrimeric ciliary kinesins. Cilia are absent in all organs
      examined, leading to the conclusion that kif3a is indispensable for ciliogenesis
      in all cells, including photoreceptors. Unexpectedly, kif3a function precedes
      ciliogenesis as ciliary basal bodies are mispositioned in mutant photoreceptors.
      This phenotype is much less pronounced in intraflagellar transport (IFT) mutants
      and reveals that kif3a has a much broader role than previously assumed. Despite
      the severity of their basal body phenotype, kif3a mutant photoreceptors survive
      longer compared to those in IFT mutants, which display much weaker basal body
      mispositioning. This effect is absent in kif3a;IFT double mutants, indicating
      that IFT proteins have ciliary transport-independent roles, which add to the
      severity of their photoreceptor phenotype. kif3a is dispensable for basal body
      docking in otic vesicle sensory epithelia and, surprisingly, short cilia form in
      mechanosensory cristae even in the absence of kif3a In contrast to Kif3a, the
      functions of the Kif3c-related protein, encoded by the kif3c-like (kif3cl) gene,
      and the homodimeric ciliary kinesin, kif17, are dispensable for photoreceptor
      morphogenesis. These studies demonstrate unexpected new roles for both ciliary
      heterotrimeric kinesins and IFT particle genes and clarify the function of kif17,
      the homodimeric ciliary kinesin gene.

PMID- 27038112
TI  - An Approximate Markov Model for the Wright-Fisher Diffusion and Its Application
      to Time Series Data.
AB  - The joint and accurate inference of selection and demography from genetic data is
      considered a particularly challenging question in population genetics, since both
      process may lead to very similar patterns of genetic diversity. However,
      additional information for disentangling these effects may be obtained by
      observing changes in allele frequencies over multiple time points. Such data are
      common in experimental evolution studies, as well as in the comparison of ancient
      and contemporary samples. Leveraging this information, however, has been
      computationally challenging, particularly when considering multilocus data sets.
      To overcome these issues, we introduce a novel, discrete approximation for
      diffusion processes, termed mean transition time approximation, which preserves
      the long-term behavior of the underlying continuous diffusion process. We then
      derive this approximation for the particular case of inferring selection and
      demography from time series data under the classic Wright-Fisher model and
      demonstrate that our approximation is well suited to describe allele trajectories
      through time, even when only a few states are used. We then develop a Bayesian
      inference approach to jointly infer the population size and locus-specific
      selection coefficients with high accuracy and further extend this model to also
      infer the rates of sequencing errors and mutations. We finally apply our approach
      to recent experimental data on the evolution of drug resistance in influenza
      virus, identifying likely targets of selection and finding evidence for much
      larger viral population sizes than previously reported.

PMID- 27038113
TI  - The Genetic Cost of Neanderthal Introgression.
AB  - Approximately 2-4% of genetic material in human populations outside Africa is
      derived from Neanderthals who interbred with anatomically modern humans. Recent
      studies have shown that this Neanderthal DNA is depleted around functional
      genomic regions; this has been suggested to be a consequence of harmful epistatic
      interactions between human and Neanderthal alleles. However, using published
      estimates of Neanderthal inbreeding and the distribution of mutational fitness
      effects, we infer that Neanderthals had at least 40% lower fitness than humans on
      average; this increased load predicts the reduction in Neanderthal introgression
      around genes without the need to invoke epistasis. We also predict a residual
      Neanderthal mutational load in non-Africans, leading to a fitness reduction of at
      least 0.5%. This effect of Neanderthal admixture has been left out of previous
      debate on mutation load differences between Africans and non-Africans. We also
      show that if many deleterious mutations are recessive, the Neanderthal admixture
      fraction could increase over time due to the protective effect of Neanderthal
      haplotypes against deleterious alleles that arose recently in the human
      population. This might partially explain why so many organisms retain gene flow
      from other species and appear to derive adaptive benefits from introgression.

PMID- 27038114
TI  - Neurofeedback training of EEG alpha rhythm enhances episodic and working memory.
AB  - Neurofeedback training (NFT) of the alpha rhythm has been used for several
      decades but is still controversial in regards to its trainability and effects on
      working memory. Alpha rhythm of the frontoparietal region are associated with
      either the intelligence or memory of healthy subjects and are also related to
      pathological states. In this study, alpha NFT effects on memory performances were
      explored. Fifty healthy participants were recruited and randomly assigned into a
      group receiving a 8-12-Hz amplitude (Alpha) or a group receiving a random 4-Hz
      amplitude from the range of 7 to 20 Hz (Ctrl). Three NFT sessions per week were
      conducted for 4 weeks. Working memory was assessed by both a backward digit span
      task and an operation span task, and episodic memory was assessed using a word
      pair task. Four questionnaires were used to assess anxiety, depression, insomnia,
      and cognitive function. The Ctrl group had no change in alpha amplitude and
      duration. In contrast, the Alpha group showed a progressive significant increase
      in the alpha amplitude and total alpha duration of the frontoparietal region.
      Accuracies of both working and episodic memories were significantly improved in a
      large proportion of participants of the Alpha group, particularly for those with
      remarkable alpha-amplitude increases. Scores of four questionnaires fell in a
      normal range before and after NFT. The current study provided supporting evidence
      for alpha trainability within a small session number compared with that of
      therapy. The findings suggested the enhancement of working and episodic memory
      through alpha NFT. Hum Brain Mapp 37:2662-2675, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27038115
TI  - Mechanically Induced Catalytic Amplification Reaction for Readout of Receptor
      Mediated Cellular Forces.
AB  - Mechanics play a fundamental role in cell biology, but detecting piconewton (pN)
      forces is challenging because of a lack of accessible and high throughput assays.
      A mechanically induced catalytic amplification reaction (MCR) for readout of
      receptor-mediated forces in cells is described. Mechanically labile DNA duplexes
      presenting ligands are surface immobilized such that specific receptor forces
      denature the duplex and thus expose a blocked primer. Amplification of primers is
      achieved using an isothermal polymerization reaction and quantified by
      fluorescence readout. As a proof of concept, the assay was used to test the
      activity of a mechanomodulatory drug and integrin adhesion receptor antibodies.
      To the best of our knowledge, this is the first example of a catalytic reaction
      triggered in response to molecular piconewton forces. The MCR may transform the
      field of mechanobiology by providing a new facile tool to detect receptor
      specific mechanics with the convenience of the polymerase chain reaction (PCR).

PMID- 27038116
TI  - Digital Imaging of the Breast: Is a Synthetic View Better?

PMID- 27038117
TI  - Unraveling How Obesity Fuels Cancer.

PMID- 27038119
TI  - Adhesion Molecules, Stem Cells, and the Microenvironment in Acute Myeloid
      Leukemia.

PMID- 27038120
TI  - Active Surveillance Gets Personal.

PMID- 27038121
TI  - Humans, Animals and the Scope of Bioethics.

PMID- 27038122
TI  - Mexican mothers' perceptions of their child's body weight.
AB  - Currently, Mexico holds one of the top rankings in childhood obesity worldwide.
      This present qualitative study aims to explore and describe mothers' perceptions
      concerning the body weight of their children and, based on these findings, be
      able to arrive at a typology. Research included 91 semi-structured interviews
      administered to mothers of children who were underweight (UW), normal weight
      (NW), overweight (OW) or obese (OB). The data were collected between June 2011
      and December 2013. The information was analysed with MAXQDA qualitative software.
      It was found that overestimated perception in UW children is observed in mothers
      who fear gaining weight. Mothers of NW children tend to gauge the weight of their
      children close to that which is normal. OW children are appropriately perceived
      by their mothers; however, these mothers are not concerned by this situation
      because for them, it is something temporary that will disappear as the child
      grows. The majority of boys who were OB were underestimated in their weight;
      those who were appropriately perceived showed class II or III obesity. Mothers
      typically perceived OW and OB girls with greater precision. The mothers who
      perceived obesity in their sons or daughters felt responsible, which motivated
      them to change their children's habits and behaviours. Therefore, health
      professionals should communicate and help these mothers recognise OW and OB
      status in their children. Furthermore, the importance of prevention should be
      stressed when a child is OW, and they should be informed of the high health risks
      that accompany obesity.

PMID- 27038123
TI  - Obesity, weight gain, and ovarian cancer risk in African American women.
AB  - Although there is growing evidence that higher adiposity increases ovarian cancer
      risk, little is known about its impact in African American (AA) women, the
      racial/ethnic group with the highest prevalence of obesity. We evaluated the
      impact of body mass index (BMI) 1 year before diagnosis and weight gain since age
      18 years on ovarian cancer risk in a population-based case-control study in AA
      women in 11 geographical areas in the US. Cases (n = 492) and age and site
      matched controls (n = 696) were identified through rapid case ascertainment and
      random-digit-dialing, respectively. Information was collected on demographic and
      lifestyle factors, including self-reported height, weight at age 18 and weight 1
      year before diagnosis/interview. Multivariable logistic regression was used to
      compute odds ratios (OR) and 95% confidence intervals (CI), adjusting for
      potential covariates. Obese women had elevated ovarian cancer risk, particularly
      for BMI >= 40 kg/m(2) compared to BMI <25 (OR = 1.72, 95% CI: 1.12-2.66; p for
      trend: 0.03). There was also a strong association with weight gain since age 18
      (OR: 1.52; 95% CI: 1.07-2.16; p for trend: 0.02) comparing the highest to lowest
      quartile. In stratified analyses by menopausal status, the association with BMI
      and weight gain was limited to postmenopausal women, with a 15% (95% CI: 1.05
      1.23) increase in risk per 5 kg/m(2) of BMI and 6% (95% CI: 1.01-1.10) increase
      in risk per 5 kg of weight gain. Excluding hormone therapy users essentially did
      not change results. Obesity and excessive adult weight gain may increase ovarian
      cancer risk in post-menopausal AA women.

PMID- 27038124
TI  - The association of incident hypertension with metabolic health and obesity
      status: definition of metabolic health does not matter.
AB  - OBJECTIVE: Metabolically healthy obese (MHO) phenotype refers to obese
      individuals with a favourable metabolic profile. Its prognostic value remains
      controversial and may partly depend on differences in how the phenotype is
      defined. We aimed to investigate whether the MHO phenotype is associated with
      future development of incident hypertension in a Korean population according to
      various definitions of metabolic health. SUBJECTS AND METHODS: The study
      population comprised 31 033 Koreans without hypertension. Participants were
      stratified into metabolically healthy nonobese (MHNO), metabolically unhealthy
      nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy
      obese (MUO) by body mass index (cut-off value, 25.0 kg/m(2) ) and metabolic
      health state, using four different definitions: Adult Treatment Panel (ATP)-III,
      Wildman, Karelis and the homoeostasis model assessment (HOMA) criteria. RESULTS:
      Over the median follow-up period of 35.0 months (range, 4.5-81.4 months), 4589 of
      the 31 033 individuals (14.8%) developed incident hypertension. Compared with the
      MHNO group, the MHO group showed increased association with incident hypertension
      with multivariate-adjusted odds ratios of 1.56 (95% confidence interval [CI],
      1.41-1.72), 1.58 (95% CI 1.42-1.75), 1.52 (95% CI 1.35-1.71) and 1.46 (95% CI
      1.33-1.61), when defined by ATP-III, Wildman, Karelis and HOMA criteria,
      respectively. CONCLUSION: MUO individuals showed the highest association with the
      incident hypertension (adjusted odds ratios up to 2.00). MHO subjects showed an
      approximately 1.5-fold higher association with incident hypertension than their
      nonobese counterpart regardless of the definition of metabolic health used. Thus,
      considering both metabolic health and obesity is important for the assessment of
      potential cardiovascular outcomes.

PMID- 27038125
TI  - Disorder transitions and conformational diversity cooperatively modulate
      biological function in proteins.
AB  - Structural differences between conformers sustain protein biological function.
      Here, we studied in a large dataset of 745 intrinsically disordered proteins, how
      ordered-disordered transitions modulate structural differences between conformers
      as derived from crystallographic data. We found that almost 50% of the proteins
      studied show no transitions and have low conformational diversity while the rest
      show transitions and a higher conformational diversity. In this last subset, 60%
      of the proteins become more ordered after ligand binding, while 40% more
      disordered. As protein conformational diversity is inherently connected with
      protein function our analysis suggests differences in structure-function
      relationships related to order-disorder transitions.

PMID- 27038126
TI  - Cloud forest trees with higher foliar water uptake capacity and anisohydric
      behavior are more vulnerable to drought and climate change.
AB  - Many tropical montane cloud forest (TMCF) trees are capable of foliar water
      uptake (FWU) during leaf-wetting events. In this study, we tested the hypothesis
      that maintenance of leaf turgor during periods of fog exposure and soil drought
      is related to species' FWU capacity. We conducted several experiments using
      apoplastic tracers, deuterium labeling and leaf immersion in water to evaluate
      differences in FWU among three common TMCF tree species. We also measured the
      effect of regular fog exposure on the leaf water potential of plants subjected to
      soil drought and used these data to model species' response to long-term drought.
      All species were able to absorb water through their leaf cuticles and/or
      trichomes, although the capacity to do so differed between species. During the
      drought experiment, the species with higher FWU capacity maintained leaf turgor
      for a longer period when exposed to fog, whereas the species with lower FWU
      exerted tighter stomatal regulation to maintain leaf turgor. Model results
      suggest that without fog, species with high FWU are more likely to lose turgor
      during seasonal droughts. We show that leaf-wetting events are essential for
      trees with high FWU, which tend to be more anisohydric, maintaining leaf turgor
      during seasonal droughts.

PMID- 27038127
TI  - Harnessing Fc receptor biology in the design of therapeutic antibodies.
AB  - The antibody Fc domain engages the small family of Fc receptors, expressed on
      cells of the immune system and beyond, to stimulate a rich diversity of positive
      and negative cell-mediated effector functions. The emergence of monoclonal
      antibodies for the treatment of various pathologic conditions has provided
      additional insights into Fc receptor biology, and has suggested new strategies to
      exploit Fc receptor interactions to create improved therapeutics. While most
      therapeutic IgGs approved to date have retained a native IgG Fc domain, the
      knowledge gained over the last decades has provided the opportunity to design
      tailored and more efficacious immunotherapies exhibiting fewer side effects and
      longer half-life. This review summarizes recent advances made in the design of
      biologics that modulate or exploit Fc receptor-IgG interactions, and describes
      innovative drugs currently under investigation in clinical trials that have been
      precisely tuned to achieve a desired therapeutic effect.

PMID- 27038128
TI  - Value of severe liver iron overload for assessing heart iron levels in
      thalassemia major patients.
AB  - PURPOSE: The relationship between severe liver iron overload (LIO) and heart iron
      overload (HIO) in transfusion-dependent patients with thalassemia major (TM) is
      uncertain. Whether severe LIO can serve as an index for assessing heart iron
      deposition has vital clinical significance. Therefore, our aim is to determine if
      a close relationship exists between severe LIO and HIO. MATERIALS AND METHODS: We
      examined 110 TM patients who underwent T2* measurement in the liver and heart on
      a 1.5 Tesla MRI scanner. Various statistical analysis methods were used to assess
      the relationship. RESULTS: Most of these patients suffered from severe LIO
      (58.18%, liver T2* < 1.4 ms). Both Pearson's and Spearman's tests showed a
      significant correlation between liver T2* and heart T2* values (with a
      correlation coefficient of 0.408 and 0.550, respectively, both P < 0.0001). A
      nonlinear model, with the equation of Heart T2* = 37.974-17.684 / Liver T2*, was
      found to be the best model to indicate the relationship between liver T2* and
      heart T2*. Receiver operating characteristic (ROC) analysis showed the area under
      the ROC curve of liver T2* and serum ferritin for predicting HIO was 0.812 (95%
      confidence interval [CI]: 0.731-0.892; P < 0.0001) and 0.69 (95% CI: 0.585-0.795;
      P = 0.001), respectively. CONCLUSION: Our preliminary data suggest the existence
      of a close relationship between severe LIO and HIO. High liver iron levels appear
      to increase the risk of heart iron deposition. This further supports the concept
      of critical liver iron concentration, above which elevated heart iron is present.
      J. MAGN. RESON. IMAGING 2016;44:880-889.

PMID- 27038129
TI  - DMSO- and Serum-Free Cryopreservation of Wharton's Jelly Tissue Isolated From
      Human Umbilical Cord.
AB  - The facile nature of mesenchymal stem cell (MSC) acquisition in relatively large
      numbers has made Wharton's jelly (WJ) tissue an alternative source of MSCs for
      regenerative medicine. However, freezing of such tissue using dimethyl sulfoxide
      (DMSO) for future use impedes its clinical utility. In this study, we compared
      the effect of two different cryoprotectants (DMSO and cocktail solution) on post
      thaw cell behavior upon freezing of WJ tissue following two different freezing
      protocols (Conventional [-1 degrees C/min] and programmed). The programmed method
      showed higher cell survival rate compared to conventional method of freezing.
      Further, cocktail solution showed better cryoprotection than DMSO. Post-thaw
      growth characteristics and stem cell behavior of Wharton's jelly mesenchymal stem
      cells (WJMSCs) from WJ tissue cryopreserved with a cocktail solution in
      conjunction with programmed method (Prog-Cock) were comparable with WJMSCs from
      fresh WJ tissue. They preserved their expression of surface markers, pluripotent
      factors, and successfully differentiated in vitro into osteocytes, adipocytes,
      chondrocytes, and hepatocytes. They also produced lesser annexin-V-positive cells
      compared to cells from WJ tissue stored using cocktail solution in conjunction
      with the conventional method (Conv-Cock). Real-time PCR and Western blot analysis
      of post-thaw WJMSCs from Conv-Cock group showed significantly increased
      expression of pro-apoptotic factors (BAX, p53, and p21) and reduced expression of
      anti-apoptotic factor (BCL2) compared to WJMSCs from the fresh and Prog-Cock
      group. Therefore, we conclude that freezing of fresh WJ tissue using cocktail
      solution in conjunction with programmed freezing method allows for an efficient
      WJ tissue banking for future MSC-based regenerative therapies. J. Cell. Biochem.
      117: 2397-2412, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038130
TI  - Universal influenza vaccines: Shifting to better vaccines.
AB  - Influenza virus causes acute upper and lower respiratory infections and is the
      most likely, among known pathogens, to cause a large epidemic in humans.
      Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced
      immunity. Furthermore, influenza viruses can cross from animals to humans,
      generating novel, potentially pandemic strains. Currently available influenza
      vaccines induce a strain specific response and may be ineffective against new
      influenza viruses. The difficulty in predicting circulating strains has
      frequently resulted in mismatch between the annual vaccine and circulating
      viruses. Low-resource countries remain mostly unprotected against seasonal
      influenza and are particularly vulnerable to future pandemics, in part, because
      investments in vaccine manufacturing and stockpiling are concentrated in high
      resource countries. Antibodies that target conserved sites in the hemagglutinin
      stalk have been isolated from humans and shown to confer protection in animal
      models, suggesting that broadly protective immunity may be possible. Several
      innovative influenza vaccine candidates are currently in preclinical or early
      clinical development. New technologies include adjuvants, synthetic peptides,
      virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and
      attenuated or inactivated influenza viruses. Other approaches target the
      conserved exposed epitope of the surface exposed membrane matrix protein M2e.
      Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are
      mainly targeted for developing strong cross-protective T cell responses. With
      multiple vaccine candidates moving along the testing and development pipeline,
      the field is steadily moving toward a product that is more potent, durable, and
      broadly protective than previously licensed vaccines.

PMID- 27038131
TI  - Vaccine effectiveness of tetanus toxoid, reduced diphtheria toxoid, and acellular
      pertussis vaccine during a pertussis outbreak in Maine.
AB  - BACKGROUND: Multiple school-associated pertussis outbreaks were reported in Maine
      from 2010 to 2011. These outbreaks were associated with an overall increase in
      pertussis cases statewide. Waning of protection in students recently vaccinated
      with tetanus, diphtheria, and acellular pertussis (Tdap) has been implicated in
      the increase in reported rates of pertussis nationally. METHODS: We conducted a
      retrospective cohort study to evaluate Tdap vaccine effectiveness (VE) among
      students aged 11-19 years in two schools reporting outbreaks in 2011. All
      pertussis cases reported from August through November, 2011 at the two schools
      were included. Vaccination history was verified using provider information, state
      vaccine registry data, and parental verification. Attack rates (AR) were
      calculated. VE and duration of protection was calculated as VE=1
      (ARvaccinated/ARunvaccinated)*100% using a log binomial regression model.
      RESULTS: Of 416 students enrolled, 314 were included in the analyses. Twenty-nine
      cases collectively in Schools A and B. Tdap coverage was 65% at School A and 42%
      at School B before the start of the outbreak. Among students enrolled in the
      study, attack rates were 11.9% and 7.7% at Schools A and B, respectively. Overall
      VE was 68.5% (95% confidence interval (CI) 37.7-86.2). VE was 70.4% (95% CI 17.5
      89.4) for School A and 65.2% (95% CI -19.2 to 89.9) for School B. VE <2 years
      versus >=2 years from outbreak onset was not significantly different.
      CONCLUSIONS: Tdap was moderately effective in preventing disease among vaccinated
      students. Vaccine coverage of 65% or less was suboptimal and might contribute to
      outbreaks. Waning VE was not demonstrated. Increased vaccination coverage rates
      as well as further evaluation of the role of acellular vaccine on VE is needed.

PMID- 27038132
TI  - A prospective cohort study assessing the reactogenicity of pertussis and
      influenza vaccines administered during pregnancy.
AB  - BACKGROUND: Pertussis vaccination during pregnancy can prevent 91% of infant
      infections. In 2015, antenatal pertussis vaccination programs were introduced
      across Australia. METHODS: To monitor the safety of this program, pregnant women
      who received trivalent influenza vaccine (TIV) and/or diphtheria-tetanus
      acellular pertussis vaccine (dTpa) were surveyed by text message seven days post
      vaccination about possible adverse events following immunization (AEFI).
      Univariate logistic regression models were used to calculate the odds of
      reporting an AEFI following dTpa compared to TIV. Similar analyses were used to
      compare AEFI reported by women who received a previous dose of dTpa in 2011/2012
      as part of a state-wide cocooning program. RESULTS: Of 5155 women, 4347 (84.3%)
      replied; 10.8% indicated they experienced an AEFI. There was no difference in the
      proportion of women who reported any reaction by vaccine; however, women who
      received dTpa were more likely to report a local reaction than women who received
      TIV (7.1% and 3.2%, respectively; OR: 2.29; 95% CI: 1.61-3.26). There was
      evidence suggesting local reactions were more common among women with a previous
      dose of dTpa (11.4%) compared to women with no previous dose (6.0%; OR: 2.00; 95%
      CI: 0.95-4.25); 11 (0.3%) women reported attending a hospital emergency
      department. Subsequent follow-up indicated symptoms resolved and mother and
      infant were healthy. There was no difference in the proportion of women attending
      hospital by vaccine (p > 0.05). DISCUSSION: Data on systemic and local reactions
      following receipt of TIV and dTpa during pregnancy support the safety of
      antenatal vaccination.

PMID- 27038133
TI  - Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after
      exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.
AB  - We recently showed that orexin expression in sudden infant death syndrome (SIDS)
      infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as
      compared with controls. Orexin maintains wakefulness/sleeping states, arousal,
      and rapid eye movement sleep, abnormalities of which have been reported in SIDS.
      This study examined the effects of two prominent risk factors for SIDS,
      intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine
      exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in
      piglets. Piglets were randomly assigned to five groups: saline control (n = 7),
      air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of
      7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles)
      (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB
      expression was quantified in the central tuberal hypothalamus [dorsal medial
      hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the
      dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures
      significantly increased: (i) orexin expression in the hypothalamus and pons; and
      (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin
      expression in the hypothalamus and pons without changing neuronal numbers. Linear
      relationships existed between the percentage of orexin-positive neurons and the
      area of pontine orexin immunoreactivity of control and exposure piglets. These
      results demonstrate that postnatal nicotine exposure increases the proportion of
      orexin-positive neurons in the hypothalamus and fibre expression in the pons, and
      that IHH exposure does not prevent the nicotine-induced increase. Thus, although
      both nicotine and IHH are risk factors for SIDS, it appears they have opposing
      effects on OxA and OxB expression, with the IHH exposure closely mimicking what
      we recently found in SIDS.

PMID- 27038134
TI  - Interventions for acne scars.
AB  - BACKGROUND: Acne scarring is a frequent complication of acne and resulting scars
      may negatively impact on an affected person's psychosocial and physical well
      being. Although a wide range of interventions have been proposed, there is a lack
      of high-quality evidence on treatments for acne scars to better inform patients
      and their healthcare providers about the most effective and safe methods of
      managing this condition. This review aimed to examine treatments for atrophic and
      hypertrophic acne scars, but we have concentrated on facial atrophic scarring.
      OBJECTIVES: To assess the effects of interventions for treating acne scars.
      SEARCH METHODS: We searched the following databases up to November 2015: the
      Cochrane Skin Group Specialised Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 10), MEDLINE
      (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five
      trials registers, and checked the reference lists of included studies and
      relevant reviews for further references to randomised controlled trials.
      SELECTION CRITERIA: We include randomised controlled trials (RCTs) which
      allocated participants (whether split-face or parallel arms) to any active
      intervention (or a combination) for treating acne scars. We excluded studies
      dealing only or mostly with keloid scars. DATA COLLECTION AND ANALYSIS: Three
      review authors independently extracted data from each of the studies included in
      this review and evaluated the risks of bias. We resolved disagreements by
      discussion and arbitration supported by a method expert as required. Our primary
      outcomes were participant-reported scar improvement and any adverse effects
      serious enough to cause participants to withdraw from the study. MAIN RESULTS: We
      included 24 trials with 789 adult participants aged 18 years or older. Twenty
      trials enrolled men and women, three trials enrolled only women and one trial
      enrolled only men. We judged eight studies to be at low risk of bias for both
      sequence generation and allocation concealment. With regard to blinding we judged
      17 studies to be at high risk of performance bias, because the participants and
      dermatologists were not blinded to the treatments administered or received;
      however, we judged all 24 trials to be at a low risk of detection bias for
      outcome assessment. We evaluated 14 comparisons of seven interventions and four
      combinations of interventions. Nine studies provided no usable data on our
      outcomes and did not contribute further to this review's results.For our outcome
      'Participant-reported scar improvement' in one study fractional laser was more
      effective in producing scar improvement than non-fractional non-ablative laser at
      week 24 (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.25 to 12.84; n =
      64; very low-quality evidence); fractional laser showed comparable scar
      improvement to fractional radiofrequency in one study at week eight (RR 0.78, 95%
      CI 0.36 to 1.68; n = 40; very low-quality evidence) and was comparable to
      combined chemical peeling with skin needling in a different study at week 48 (RR
      1.00, 95% CI 0.60 to 1.67; n = 26; very low-quality evidence). In a further study
      chemical peeling showed comparable scar improvement to combined chemical peeling
      with skin needling at week 32 (RR 1.24, 95% CI 0.87 to 1.75; n = 20; very low
      quality evidence). Chemical peeling in one study showed comparable scar
      improvement to skin needling at week four (RR 1.13, 95% CI 0.69 to 1.83; n = 27;
      very low-quality evidence). In another study, injectable fillers provided better
      scar improvement compared to placebo at week 24 (RR 1.84, 95% CI 1.31 to 2.59; n
      = 147 moderate-quality evidence).For our outcome 'Serious adverse effects' in one
      study chemical peeling was not tolerable in 7/43 (16%) participants (RR 5.45, 95%
      CI 0.33 to 90.14; n = 58; very low-quality evidence).For our secondary outcome
      'Participant-reported short-term adverse events', all participants reported pain
      in the following studies: in one study comparing fractional laser to non
      fractional non-ablative laser (RR 1.00, 95% CI 0.94 to 1.06; n = 64; very low
      quality evidence); in another study comparing fractional laser to combined
      peeling plus needling (RR 1.00, 95% CI 0.86 to 1.16; n = 25; very low-quality
      evidence); in a study comparing chemical peeling plus needling to chemical
      peeling (RR 1.00, 95% CI 0.83 to 1.20; n = 20; very low-quality evidence); in a
      study comparing chemical peeling to skin needling (RR 1.00, 95% CI 0.87 to 1.15;
      n = 27; very low-quality evidence); and also in a study comparing injectable
      filler and placebo (RR 1.03, 95% CI 0.10 to 11.10; n = 147; low-quality
      evidence).For our outcome 'Investigator-assessed short-term adverse events',
      fractional laser (6/32) was associated with a reduced risk of hyperpigmentation
      than non-fractional non-ablative laser (10/32) in one study (RR 0.60, 95% CI 0.25
      to 1.45; n = 64; very low-quality evidence); chemical peeling was associated with
      increased risk of hyperpigmentation (6/12) compared to skin needling (0/15) in
      one study (RR 16.00, 95% CI 0.99 to 258.36; n = 27; low-quality evidence). There
      was no difference in the reported adverse events with injectable filler (17/97)
      compared to placebo (13/50) (RR 0.67, 95% CI 0.36 to 1.27; n = 147; low-quality
      evidence). AUTHORS' CONCLUSIONS: There is a lack of high-quality evidence about
      the effects of different interventions for treating acne scars because of poor
      methodology, underpowered studies, lack of standardised improvement assessments,
      and different baseline variables.There is moderate-quality evidence that
      injectable filler might be effective for treating atrophic acne scars; however,
      no studies have assessed long-term effects, the longest follow-up being 48 weeks
      in one study only. Other studies included active comparators, but in the absence
      of studies that establish efficacy compared to placebo or sham interventions, it
      is possible that finding no evidence of difference between two active treatments
      could mean that neither approach works. The results of this review do not provide
      support for the first-line use of any intervention in the treatment of acne
      scars.Although our aim was to identify important gaps for further primary
      research, it might be that placebo and or sham trials are needed to establish
      whether any of the active treatments produce meaningful patient benefits over the
      long term.

PMID- 27038135
TI  - Understanding the Origins of Nucleophilic Hydride Reactivity of a Sodium Hydride
      Iodide Composite.
AB  - Sodium hydride (NaH) has been commonly used as a Bronsted base in chemical
      syntheses, while it has rarely been employed to add hydride (H(-) ) to
      unsaturated electrophiles. We previously developed a procedure to activate NaH
      through the addition of a soluble iodide source and found that the new NaH-NaI
      composite can effect even stereoselective nucleophilic hydride reductions of
      nitriles, imines, and carbonyl compounds. In this work, we report that mixing NaH
      with NaI or LiI in tetrahydrofuran (THF) as a solvent provides a new inorganic
      composite, which consists of NaI interspersed with activated NaH, as revealed by
      powder X-ray diffraction, and both solid-state NMR and X-ray photoelectron
      spectroscopies. DFT calculations imply that this remarkably simple inorganic
      composite, which is comprised of NaH and NaI, gains nucleophilic hydridic
      character similar to covalent hydrides, resulting in unprecedented and unique
      hydride donor chemical reactivity.

PMID- 27038136
TI  - A four-phase strategy for the implementation of reflectance confocal microscopy
      in dermatology.
AB  - BACKGROUND: Reflectance confocal microscopy (RCM) is gradually implemented in
      dermatology. Strategies for further implementation and practical 'hands on'
      guidelines are lacking. OBJECTIVE: The primary outcome was to conduct a general
      strategy for further implementation of RCM. The secondary outcome was the
      diagnosis of psoriasis and differentiation of stable from unstable psoriatic
      plaques by means of the 'hands on' protocol, derived from the strategy. METHODS:
      We used a four-phased model; an exploring phase, a systematic literature search,
      a clinical approach and, finally, an integration phase to develop a clinical
      guideline for RCM in psoriasis. Receiver operating characteristic curve
      statistics was applied to define the accuracy for the diagnosis of unstable
      psoriasis. RESULTS: A general strategy for further implementation of RCM and
      practical approach was developed to examine psoriasis by RCM and to distinguish
      stable from unstable psoriasis. Unstable psoriasis was diagnosed by epidermal
      inflammatory cell counts with a sensitivity and specificity of 91.7% and 98.3%,
      respectively, and with an accuracy of 0.92 (area under the curve). In addition, a
      monitoring model was proposed. CONCLUSION: This is the first study that shows a
      method for implementation of RCM in dermatology. The strategy and hands on
      protocol for psoriasis may serve as a model for other dermatological entities and
      additionally may lead to specialized ready-to-use RCM protocols for clinical
      dermatological practice.

PMID- 27038137
TI  - Reprint of: Diabetes in Kearns-Sayre Syndrome: More Common than Anticipated.

PMID- 27038138
TI  - Low Vital Capacity Was Associated with Incident Diabetes in a Japanese Health
      Screening Population in Whom Obesity Was Not Prevalent.
AB  - OBJECTIVES: There have been few studies regarding the relationship between
      respiratory function and incident diabetes in East Asian populations in whom
      obesity is not prevalent. METHODS: This is a 6-year follow-up study in a Japanese
      health-screening population that included 1874 men and 1093 women. Using Cox
      regression models, hazard ratios (HRs) of incident diabetes for percent vital
      capacity (%VC) and forced expiratory volume in 1 second divided by forced vital
      capacity (FEV1/FVC) were calculated. Diabetes was defined as simultaneous fasting
      plasma glucose (FPG) >=7.0 mmol/L and glycated hemoglobin (A1C) >=6.5% or use of
      antidiabetic medications. RESULTS: During the 6-year follow-up period (mean of
      4.8 years), 71 men (3.8%) and 18 women (1.7%) developed diabetes. The HRs (95%
      confidence intervals [CIs]) of incident diabetes for each 1 SD increase in %VC
      and the lowest tertile of %VC compared with the highest tertile were 0.81 (0.66
      to 1.00) (p=0.045) and 1.78 (1.01 to 3.16) (p=0.048), respectively, adjusted for
      sex, age, body mass index, antihypertensive drug use and A1C levels. After
      further adjustment for log high-sensitivity C-reactive protein, the HRs (95% CI)
      of incident diabetes for each 1 SD increase in %VC and the lowest tertile of %VC
      were 0.82 (0.67 to 1.01) (p=0.063) and 1.69 (0.95 to 3.01) (p=0.073),
      respectively. The association between FEV1/FVC and incident diabetes was not
      significant. CONCLUSIONS: %VC, but not FEV1/FVC, was significantly associated
      with incident diabetes in a Japanese health-screening population in whom obesity
      was not prevalent.

PMID- 27038139
TI  - Barriers to Active Lifestyles in Children with Type 1 Diabetes.
AB  - OBJECTIVES: To identify the main barriers to active lifestyles in children with
      type 1 diabetes based on known barriers in adults with type 1 diabetes. METHODS:
      Children with type 1 diabetes (n=201) recruited from the Centre Hospitalier
      Universitaire (CHU) Sainte-Justine Diabetes Clinic answered a specific
      questionnaire, the Barriers to Physical Activity in Type 1 Diabetes (BAPAD1),
      which assesses perceived barriers and parental support in the children's adoption
      of active lifestyles. RESULTS: In younger individuals (those younger than 12
      years of age), the highest barrier scores were loss of control of diabetes, fear
      of hypoglycemia, work schedule and external temperature. In the older group
      (those >=12 years of age), fear of hypoglycemia, external temperature, loss of
      control of diabetes and low fitness levels were the most important. Greater
      parental support was associated with lower overall barrier scores in younger and
      older children alike (r=-0.71 and r=-0.65, respectively; p<0.001). CONCLUSIONS:
      There are some differences in barriers to active lifestyles between younger and
      older children with type 1 diabetes. Parental support appears to be the key to
      active lifestyles in their children.

PMID- 27038140
TI  - Pharmacokinetics of drugs for pediatric pulmonary hypertension.
AB  - BACKGROUND: Over the past few years, several drugs, each with a different
      mechanism, have been developed for the treatment of pulmonary hypertension (PH)
      and are now prescribed in the clinical setting. While the optimal doses of these
      drugs in adults have been determined, the optimal dose in children, however, is
      unclear. The aim of this study was therefore, to measure blood drug levels and
      analyze the pharmacokinetics of two such drugs in children. METHODS: From April
      2010 to May 2015, we prospectively enrolled 23 children with PH for treatment
      with bosentan and/or tadalafil. Twenty children were treated with bosentan and 19
      received tadalafil. Sixteen children were given both drugs. Blood samples were
      collected after 2 weeks of treatment, and blood drug levels measured using high
      performance liquid chromatography. RESULTS: For both drugs, the peak plasma
      concentration was lower and the half-life was shorter than the known values in
      adults. The blood trough level of bosentan significantly correlated with its
      dose, but no such correlation was seen for tadalafil. For both drugs, no
      correlation was observed between age and blood drug levels. CONCLUSIONS: Oral
      dosing with bosentan and tadalafil in children may not achieve therapeutic blood
      concentration. Thus, the optimal dosing must be established individually while
      monitoring blood drug level.

PMID- 27038141
TI  - Identification of genes in longissimus dorsi muscle differentially expressed
      between Wannanhua and Yorkshire pigs using RNA-sequencing.
AB  - Western commercial pig breeds have been intensively selected, resulting in a
      sizeable, rapid and efficient accretion of muscle but a reduction in meat
      quality. When compared with Western commercial pig breeds, Chinese indigenous pig
      breeds exhibited slower growth rates and reduced lean meat content but superior
      perceived meat quality. To study the factors that determine meat quality, we
      examined piglets of one Western commercial breed (Yorkshire) and one Chinese
      indigenous breed (Wannanhua) and sequenced the longissimus dorsi muscle using RNA
      sequencing (RNA-seq). We analyzed their transcriptomes, focusing on identifying
      candidate genes that may influence porcine muscle growth, meat quality and
      adipose deposition. Gene Ontology functional enrichment and pathway enrichment
      analyses identified differentially expressed genes (DEGs) primarily associated
      with glycolytic metabolism, biological processes of muscle development and
      signaling pathways related to fatty acid metabolism, growth and carcass traits.
      This finding suggests that the DEGs may play important roles in determining meat
      quality traits. Quantitative real-time reverse transcription polymerase chain
      reaction confirmed the differential expression of 12 selected DEG. This study
      identified a number of novel candidate genes for porcine meat quality and carcass
      traits that merit further investigation to elucidate the molecular mechanisms
      responsible for muscle growth and fat deposition. 

PMID- 27038142
TI  - The real role of pseudokinase: linking diabetes to cancers.
AB  - A recent paper in Nature Communications shows that pseudokinase TRIB3 has a
      critical role in the development of diabetes-related cancers via interacting with
      SQSTM1, a selective autophagy receptor. Interrupting the TRIB3-SQSTM1 interaction
      using an alpha-helix peptide shows a significant antitumor effect both in normal
      and diabetic mice. This work provides a potential strategy against cancers in
      patients with diabetes.

PMID- 27038143
TI  - High-Current-Density Vertical-Tunneling Transistors from Graphene/Highly Doped
      Silicon Heterostructures.
AB  - Scalable fabrication of vertical-tunneling transistors is presented based on
      heterostructures formed between graphene, highly doped silicon, and its native
      oxide. Benefiting from the large density of states of highly doped silicon, the
      tunneling transistors can deliver a current density over 20 A cm(-2) . This study
      demonstrates that the interfacial native oxide plays a crucial role in governing
      the carrier transport in graphene-silicon heterostructures. 

PMID- 27038144
TI  - Connecting Eating Pathology with Risk for Engaging in Suicidal Behavior: The
      Mediating Role of Experiential Avoidance.
AB  - Individuals with eating pathology, particularly those with diagnosed eating
      disorders, are at high risk for suicide. It is less clear whether undiagnosed
      eating pathology and subsyndromal eating disorders carry the same risk and, if
      so, what mechanisms may explain why higher levels of eating pathology yield
      greater risk for engaging in suicidal behaviors. The indirect relationship
      between disordered eating and risk for suicidal behaviors via facets of
      experiential avoidance was tested using a multiple-mediator model. The model was
      tested using bootstrapping estimates of indirect effects in a sample of 218
      noncollege student adults (Mage = 32.33, 66.1% women) with a history of suicidal
      attempt and/or history of nonsuicidal self-injury (NSSI). Results revealed that
      disordered eating indirectly predicted risk for suicidal behaviors, distress
      aversion (i.e., negative attitudes or dislike of distress), and procrastination
      (i.e., delaying engagement with distressing activities). Results suggest that
      targeting experiential avoidance and helping those who have a history of engaging
      in suicidal behaviors and/or NSSI develop regulation strategies to use during
      times of distress may be of utmost importance for treatment and prevention of
      eating pathology.

PMID- 27038145
TI  - Early sorafenib-related adverse events predict therapy response of TACE plus
      sorafenib: A multicenter clinical study of 606 HCC patients.
AB  - The purpose of our study was to test the hypothesis that sorafenib-related
      dermatologic adverse events (AEs) as an early biomarker can predict the long-term
      outcomes following the combination therapy of transarterial chemoembolization
      (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma
      patients who received either TACE-S or TACE-alone treatment were consecutively
      included into analysis. In the TACE-S group, patients with >= grade 2
      dermatologic AEs within the first month of sorafenib initiation were defined as
      responders; whereas those with < grade 2 were defined as nonresponders. In the
      TACE-S group, the median overall survival (OS) of the responders was
      significantly longer than that of nonresponders (28.9 months vs. 16.8 months,
      respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders
      were significantly associated with an increased risk of death compared with
      responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The
      survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8)
      among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among
      those who received TACE-alone (p = 0.046). The median time to progression was
      13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was
      significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4
      13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic
      AEs are clinical biomarkers to identify responders from all of the patients for
      TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can
      predict the efficacy of TACE-S in future randomized controlled trials. 

PMID- 27038147
TI  - Colo-Plastics: a new surgical sub-specialty.

PMID- 27038150
TI  - Erratum.

PMID- 27038152
TI  - Transthoracic Echocardiography-Guided Percutaneous Patent Ductus Arteriosus
      Occlusion: A New Strategy for Interventional Treatment.
AB  - INTRODUCTION: Percutaneous patent ductus arteriosus (PDA) occlusion has become
      the preferred therapeutic option, which uses fluoroscopy as the guidance. To
      reduce the x-ray exposure, PDA occlusion using the Amplatzer Duct Occluder II
      (ADO II) under guidance of transthoracic echocardiography only was conducted.
      This single center study aims to access the safety and efficiency of this new
      strategy. METHODS AND RESULTS: From June 2013 to May 2015, 63 consecutive PDA
      patients underwent transthoracic echocardiography-guided PDA occlusion through
      the femoral artery. Outpatient follow-up was conducted at 1, 3, and 6 months, and
      yearly. Sixty-two patients successfully underwent echocardiography-guided
      percutaneous PDA occlusion. One patient was converted to minimally invasive
      transthoracic occlusion due to failure of delivery sheath passage through
      tortuous PDA. Mean procedure duration was 24.3 +/- 7.0 minutes; ADO II diameter
      averaged 4.6 +/- 0.9 mm; 8 cases showed traces of residual shunt immediately
      after operation which resolved after 24 hours; and mean hospital stay was 3.4 +/-
      0.5 days. There was no occluder migration, hemolysis, pericardial effusion,
      pulmonary branch or aortic stenosis at mean 13.5 +/- 4.8 months follow-up.
      CONCLUSIONS: This study demonstrated that percutaneous PDA occlusion can be
      successfully performed under guidance of transthoracic echocardiography only and
      appears safe and effective while avoiding radiation and contrast agent use.

PMID- 27038153
TI  - Effect of parent-delivered action observation therapy on upper limb function in
      unilateral cerebral palsy: a randomized controlled trial.
AB  - AIM: To determine whether home-based, parent-delivered therapy comprising action
      observation (AO) and repeated practice (RP) improves upper limb function more
      than RP alone in children with unilateral cerebral palsy (UCP). METHOD:  DESIGN:
      single-blinded parallel-group randomized controlled trial with 1:1 allocation
      comparing AO+RP (intervention) with RP alone (control). RANDOMIZATION: computer
      generated, with allocation concealment by opaque sequentially-numbered envelopes.
      SETTING: northern England, August 2011 to September 2013. PARTICIPANTS: 70
      children with UCP; mean age 5.6 years (SD 2.1), 31 female. INTERVENTION: home
      based activities were provided, tailored to interests and abilities. DURATION: 15
      minutes/day, 5 days/week for 3 months. ASSESSMENTS: Assisting Hand Assessment
      (AHA; primary outcome measure), Melbourne Assessment 2 (MA2), and ABILHAND-Kids
      at baseline, 3 months, and 6 months. RESULTS: Outcome data was available at 3
      months for 28 children in the AO+RP group and 31 controls, and at 6 months for 26
      and 28 children respectively. There were no between-group differences in AHA,
      MA2, or ABILHAND-Kids at 3 or 6 months versus baseline (all p>0.05). Combined
      group improvements (p<0.001), observed in AHA and MA2 at 3 months, were
      maintained at 6 months. ABILHAND-Kids also showed improvement at 3 months
      (p=0.003), maintained at 6 months. INTERPRETATION: Parent-delivered RP (with or
      without AO) improves upper limb function and could supplement therapist input.

PMID- 27038154
TI  - High Frequency of CYP2D6 Ultrarapid Metabolizer Genotype in the Finnish
      Population.
AB  - CYP2D6 participates in the biotransformation of many commonly used drugs. Large
      genetic variability in CYP2D6 results in a wide interindividual variability in
      the response to CYP2D6 substrate drugs. Previous studies have assessed the
      phenotype and genotype distributions of CYP2D6 in relatively small Finnish
      population samples. The aim of our study was to investigate the frequencies of
      CYP2D6 genotypes in a larger Finnish population cohort of 857 healthy volunteers.
      The volunteers were genotyped for 10 CYP2D6 genetic variants (*2, *3, *4, *5, *6,
      *9, *10, *17, *39, *41) and copy number variation performed with TaqMan
      genotyping assays and copy number assay targeting exon 9. CYP2D6 phenotypes were
      inferred from the genotype data with the classical and activity score methods.
      According to the classical method, a large majority of the study cases were
      extensive metabolizers (EM; 87.3%; 95% confidence interval 84.9-89.3) and the
      second largest group was ultrarapid metabolizers (UM; 7.2%; 5.7-9.2%).
      Intermediate (IM) and poor metabolizers (PM) were in clear minority (3.0%; 2.1
      4.4% and 2.3%; 1.5-3.6%, respectively). The activity score method yielded similar
      phenotype predictions. These results show that the frequency of UM genotype is
      higher and that of PM and IM genotype is lower in the Finnish population than in
      other North European populations. Accordingly, CYP2D6 genetic profile of the
      Finnish population differs from its geographically close neighbours, which has
      implications for the effective and safe use of drugs metabolized by CYP2D6. 

PMID- 27038155
TI  - Characterization and expression profiling of MYB transcription factors against
      stresses and during male organ development in Chinese cabbage (Brassica rapa ssp.
      pekinensis).
AB  - MYB proteins comprise a large family of plant transcription factors that play
      regulatory roles in different biological processes such as plant development,
      metabolism, and defense responses. To gain insight into this gene superfamily and
      to elucidate its roles in stress resistance, we performed a comprehensive genome
      wide identification, characterization, and expression analysis of MYB genes in
      Chinese cabbage (Brassica rapa ssp. pekinensis). We identified 475 Chinese
      cabbage MYB genes, among which most were from R2R3-MYB (256 genes) and MYB
      related (202) subfamilies. Analysis of sequence characteristics, phylogenetic
      classification, and protein motif structures confirmed the existence of several
      categories (1R, 2R, 3R, 4R, and 5R) of Chinese cabbage MYB genes, which is
      comparable with MYB genes of other crops. An extensive in silico functional
      analysis, based on established functional properties of MYB genes from different
      crop species, revealed 11 and four functional clades within the Chinese cabbage
      R2R3-MYB and MYB-related subfamilies, respectively. In this study, we reported a
      MYB-like group within the MYB-related subfamily contains 77 MYB genes. Expression
      analysis using low temperature-treated whole-genome microarray data revealed
      variable transcript abundance of 1R/2R/3R/4R/5R-MYB genes in 11 clusters between
      two inbred lines of Chinese cabbage, Chiifu and Kenshin, which differ in cold
      tolerance. In further validation tests, we used qRT-PCR to examine the cold
      responsive expression patterns of 27 BrMYB genes; surprisingly, the MYB-related
      genes were induced more highly than the R2R3-MYB genes. In addition, we
      identified 10 genes with corresponsive expression patterns from a set of salt-,
      drought-, ABA-, JA-, and SA-induced R2R3-MYB genes. We identified 11 R2R3-MYBs
      functioning in resistance against biotic stress, including 10 against Fusarium
      oxysporum f.sp. conglutinans and one against Pectobacterium carotovoram subsp.
      caratovorum. Furthermore, based on organ-specific expression data, we identified
      nine R2R3-MYBs that were constitutively expressed in male reproductive tissue,
      which may provide an important key for studying male sterility in Chinese
      cabbage. The extensive annotation and transcriptome profiling reported in this
      study will be useful for understanding the involvement of MYB genes in stress
      resistance in addition to their growth regulatory functions, ultimately providing
      the basis for functional characterization and exploitation of the candidate MYB
      genes for genetic engineering of Chinese cabbage. 

PMID- 27038156
TI  - Can you perceive ensembles without perceiving individuals?: The role of
      statistical perception in determining whether awareness overflows access.
AB  - Do we see more than we can report? Psychologists and philosophers have been hotly
      debating this question, in part because both possibilities are supported by
      suggestive evidence. On one hand, phenomena such as inattentional blindness and
      change blindness suggest that visual awareness is especially sparse. On the other
      hand, experiments relating to iconic memory suggest that our in-the-moment
      awareness of the world is much richer than can be reported. Recent research has
      attempted to resolve this debate by showing that observers can accurately report
      the color diversity of a quickly flashed group of letters, even for letters that
      are unattended. If this ability requires awareness of the individual letters'
      colors, then this may count as a clear case of conscious awareness overflowing
      cognitive access. Here we explored this requirement directly: can we perceive
      ensemble properties of scenes even without being aware of the relevant individual
      features? Across several experiments that combined aspects of iconic memory with
      measures of change blindness, we show that observers can accurately report the
      color diversity of unattended stimuli, even while their self-reported awareness
      of the individual elements is coarse or nonexistent-and even while they are
      completely blind to situations in which each individual element changes color mid
      trial throughout the entire experiment. We conclude that awareness of statistical
      properties may occur in the absence of awareness of individual features, and that
      such results are fully consistent with sparse visual awareness. 

PMID- 27038157
TI  - Study of Glycine and Folic Acid Supplementation to Ameliorate Transfusion
      Dependence in Congenital SLC25A38 Mutated Sideroblastic Anemia.
AB  - Congenital sideroblastic anemia (CSA) is a hematological disorder characterized
      by the presence of ringed sideroblasts in bone marrow erythroid precursors.
      Mutations in the erythroid-specific glycine mitochondrial transporter gene
      SLC25A38 have been found in a subset of patients with transfusion-dependent
      congenital CSA. Further studies in a zebrafish model identified a promising
      ameliorative strategy with combined supplementation with glycine and folate. We
      tested this combination in three individuals with SLC25A38 CSA, with a primary
      objective to decrease red blood cell transfusion requirements. No significant
      impact was observed on transfusion requirements or any hematologic parameters.

PMID- 27038158
TI  - Effects of paclitaxel on permanent head and neck squamous cell carcinoma cell
      lines and identification of anti-apoptotic caspase 9b.
AB  - PURPOSE: Paclitaxel is an effective chemotherapeutic agent against various human
      tumors inducing apoptosis via binding to beta-tubulin of microtubules and
      arresting cells mainly in the G2/M phase of the cell cycle. However, the
      underlying specific molecular mechanisms of paclitaxel on head and neck squamous
      cell carcinoma (HNSCC) have not been identified yet. METHODS: The apoptotic
      effects and mechanisms of paclitaxel on different permanent HPV-negative HNSCC
      cell lines (UT-SCC-24A, UT-SCC-24B, UT-SCC-60A and UT-SCC-60B) were determined by
      flow cytometry assays, polymerase chain reaction analysis, immunofluorescence
      based assays and sequencing studies. RESULTS: Paclitaxel induced a G2/M arrest in
      HNSCC cell lines followed by an increased amount of apoptotic cells. Moreover,
      the activation of caspase 8, caspase 10 and caspase 3, and the loss of the
      mitochondrial outer membrane potential could be observed, whereas an activation
      of caspase 9 could barely be detected. The efficient activation of caspase 9 was
      not affected by altered methylation patterns. Our results can show that the
      promoter region of apoptotic protease activating factor 1 (Apaf-1) was not
      methylated in the HNSCC cell lines. By sequencing analysis two isoforms of
      caspase 9, the pro-apoptotic caspase 9 and the anti-apoptotic caspase 9b were
      identified. The anti-apoptotic caspase 9b is missing the catalytic site and acts
      as an endogenous inhibitor of apoptosis by blocking the binding of caspase 9 to
      Apaf-1 to form the apoptosome. CONCLUSION: Our data indicate the presence of anti
      apoptotic caspase 9b in HNSCC, which may serve as a promising target to increase
      chemotherapeutic apoptosis induction.

PMID- 27038159
TI  - Comparative Analysis of the Effects of Two Probiotic Bacterial Strains on
      Metabolism and Innate Immunity in the RAW 264.7 Murine Macrophage Cell Line.
AB  - Probiotic and potential probiotic bacterial strains are routinely prescribed and
      used as supplementary therapy for a variety infectious diseases, including
      enteric disorders among a wide range of individuals. While there are an
      increasing number of studies defining the possible mechanisms of probiotic
      activity, a great deal remains unknown regarding the diverse modes of action
      attributed to these therapeutic agents. More precise information is required to
      support the appropriate application of probiotics. To address this objective, we
      selected two probiotics strains, Lactobacillus acidophilus MTCC-10307 (LA) and
      Bacillus clausii MTCC-8326 (BC) that are frequently prescribed for the treatment
      of intestinal disorders and investigated their effects on the RAW 264.7 murine
      macrophage cell line. Our results reveal that LA and BC are potent activators of
      both metabolic activity and innate immune responses in these cells. We also
      observed that LA and BC possessed similar activity in preventing infection
      simulated in vitro in murine macrophages by Salmonella typhimurium serovar
      enterica.

PMID- 27038160
TI  - A Scoping Study on the Ethics of Health Systems Research.
AB  - Currently, health systems research (HSR) is reviewed by the same ethical
      standards as clinical research, which has recently been argued in the literature
      to be an inappropriate standard of evaluation. The issues unique to HSR warrant a
      different review by research ethics committees (RECs), as it does not impose the
      same risks to study participants as other types of clinical or public health
      research. However, there are limited tools and supporting documents that clarify
      the ethical considerations. Therefore, there is a need for additional reflection
      around ethical review of HSR and their consideration by RECs. The purpose of this
      paper is to review, understand, and synthesize the current state of literature
      and practice to inform these deliberations and the larger discourse on ethics
      review guidelines for HSR. This paper presents a review of the literature on
      ethics of HSR in the biomedical, public health, and implementation research to
      identify ethical considerations specific to HSR; and to identify examples of
      commonly available guidance and/or tools for the ethical review of HSR studies.
      Fifteen articles were identified on HSR ethics issues, and forty-two
      international academic institutions were contacted (of the responses (n=29), no
      institution had special ethical guidelines for reviewing HSR) about their HSR
      ethics review guidelines. There appears to be a clear gap in the current health
      research ethics discourse around health systems research ethics. This review
      serves as a first step (to better understand the current status) towards a larger
      dialogue on the topic.

PMID- 27038161
TI  - Urine biochemistry assessment in critically ill patients: controversies and
      future perspectives.
AB  - In the past, urine biochemistry was a major tool in acute kidney injury (AKI)
      management. Classic papers published some decades ago established the values of
      the urine indices which were thought to distinguish "pre-renal" (functional) AKI
      attributed to low renal perfusion and "renal" (structural) AKI attributed to
      acute tubular necrosis (ATN). However, there were a lot of drawbacks and
      limitations in these studies and some recent articles have questioned the utility
      of measuring urine electrolytes especially because they do not seem to adequately
      inform about renal perfusion nor AKI duration (transient vs. persistent). At the
      same time, the "pre-renal" paradigm has been consistently criticized because
      hypoperfusion followed by ischemia and ATN does not seem to explain most of the
      AKI developing in critically ill patients and distinct AKI durations do not seem
      to be clearly related to different pathophysiological mechanisms or
      histopathological findings. In this new context, other possible roles for urine
      biochemistry have emerged. Some studies have suggested standardized changes in
      the urine electrolyte composition preceding increases in serum creatinine
      independently of AKI subsequent duration, which might actually be due to intra
      renal microcirculatory changes and activation of sodium-retaining mechanisms even
      in the absence of impaired global renal blood flow. In the present review, the
      points of controversy regarding urine biochemistry assessment were evaluated as
      well as future perspectives for its role in AKI monitoring. An alternative
      approach for the interpretation of measured urine electrolytes is proposed which
      needs further larger studies to be validated and incorporated in daily ICU
      practice.

PMID- 27038162
TI  - The venous-arterial partial pressure of carbon dioxide as a new monitoring of
      circulatory disorder: no so simple.

PMID- 27038163
TI  - Transit times and mean ages for nonautonomous and autonomous compartmental
      systems.
AB  - We develop a theory for transit times and mean ages for nonautonomous
      compartmental systems. Using the McKendrick-von Forster equation, we show that
      the mean ages of mass in a compartmental system satisfy a linear nonautonomous
      ordinary differential equation that is exponentially stable. We then define a
      nonautonomous version of transit time as the mean age of mass leaving the
      compartmental system at a particular time and show that our nonautonomous theory
      generalises the autonomous case. We apply these results to study a nine
      dimensional nonautonomous compartmental system modeling the terrestrial carbon
      cycle, which is a modification of the Carnegie-Ames-Stanford approach model, and
      we demonstrate that the nonautonomous versions of transit time and mean age
      differ significantly from the autonomous quantities when calculated for that
      model.

PMID- 27038164
TI  - On Hill coefficients and subunit interaction energies.
AB  - The study of cooperative ligand binding to multimeric proteins aims to explain
      complex cooperative binding phenomena using concepts derived from ideal binding
      isotherms. The purpose of such efforts is the dissection of the cooperative
      binding isotherm into its interacting components, a result with a clear
      mechanistic value. Historically, cooperative binding is usually quantified using
      the Hill coefficient, [Formula: see text], defined as the slope of the Hill plot
      at 50 % saturation. It was previously shown that the slope of the Hill plot
      throughout the titration is equal to the ratio of the binding variance in the
      system under study, to the binding variance of a reference non-interacting
      system. In the present contribution, this leads to a broader approach towards
      quantifying cooperativity, which empirically links cooperativity to the ensemble
      average of the subunit interaction energy. The resulting equations can be used to
      derive average differential subunit interaction energies directly from
      experimental binding isotherms. Combined with recent experimental advances in
      assessing binding distributions in multimeric proteins, these equations can also
      be used to calculate individual subunit interaction energies for specific n
      ligated protein species.

PMID- 27038165
TI  - Pupillary correlates of lapses of sustained attention.
AB  - The current study examined the extent to which pupillary responses (both pretrial
      baseline and phasic responses) would accurately track lapses of attention as
      predicted by theories of locus coeruleus norepinephrine (LC-NE) functioning.
      Participants performed a sustained attention task while pupil responses were
      continuously recorded. Periodically during the task, participants were presented
      with thought probes to determine if they were on or off task. The results
      suggested the pupillary responses accurately distinguished on from off-task
      states. Importantly, pretrial baseline pupil responses distinguished different
      types of lapses of attention, with inattentive and mind-wandering states being
      associated with small pretrial baseline pupil diameters on average and distracted
      states being associated with larger pretrial baseline pupil diameters on average
      compared to focused states. These results support the notion that pupil diameter
      is sensitive to different types of lapses of attention which may be associated
      with different LC-NE modes. 

PMID- 27038166
TI  - Antiepileptic drugs with histone deacetylase inhibition activity and prostate
      cancer risk: a population-based case-control study.
AB  - Previous studies suggest that antiepileptic drugs with histone deacetylase (HDAC)
      inhibitor properties may have prostate cancer preventive effects. We evaluated
      the association between antiepileptic drug use and prostate cancer risk in a
      population-based case-control study. The study included all new prostate cancer
      cases diagnosed in Finland in 1995-2002 and matched controls (24,657 case-control
      pairs) identified from the Finnish Cancer Registry and the Population Register
      Center, respectively. Information on antiepileptic drug purchases was obtained
      from the national prescription reimbursement database. Odds ratios and their 95 %
      confidence intervals were estimated using age-adjusted and multivariable-adjusted
      conditional logistic regression analysis. Compared to never-users of
      antiepileptic drugs, the overall prostate cancer risk was decreased among users
      of phenobarbital, carbamazepine, and valproic acid (multivariable-adjusted odds
      ratio (OR) 0.47, 95 % CI 0.24-0.92; OR 0.82, 95 % CI 0.71-0.94, and OR 0.62, 95 %
      CI 0.42-0.92, respectively), but not among users of other antiepileptic drugs.
      Overall prostate cancer risk decreased in a dose-dependent manner by cumulative
      amount, duration and yearly dosage (intensity) of HDAC inhibitors valproic acid
      and carbamazepine. The risk of advanced prostate cancer was decreased only among
      carbamazepine users (OR 0.65, 95 % CI 0.44-0.96). Our results support possible
      prostate cancer preventive effects of HDAC inhibitors. However, also
      phenobarbital use was associated with decreased prostate cancer risk, despite not
      having HDAC inhibiting activity. The mechanism of action for antiepileptic drugs
      in prostate cancer deserves further study.

PMID- 27038167
TI  - Twin-like appearance of an unruptured intracerebral anterior communicating artery
      (ACom) aneurysm in a male sibling of a patient with a ruptured ACom aneurysm.
AB  - BACKGROUND: Increased risk of intracranial aneurysm rupture with subsequent
      subarachnoid haemorrhage (SAH) is related to several possible factors, including
      first-grade familial aneurysms. METHODS AND RESULTS: Here we present a case of
      one ruptured and one unruptured identical twin-like anterior communicating artery
      (ACom) aneurysm present in two male siblings, without any proven genetic
      predisposition. According to evidence-based scores, aneurysm rupture risk for the
      younger (51 years old) sibling (with an unruptured ACom aneurysm) would be low,
      leaving the decision for either treatment or clinical follow-up to the discretion
      of the treating physician. CONCLUSIONS: From a clinical neurosurgical
      perspective, however, especially since his older brother suffered an aneurysmal
      SAH at age 57 (i.e. 6 life-years later) from a twin-like-appearing ACom aneurysm,
      in our opinion rupture seems almost inevitable, thus prompting treatment at an
      early stage.

PMID- 27038168
TI  - Reconstructive endovascular treatment of ruptured vertebral artery dissection
      involving the posterior inferior cerebellar artery.
AB  - Two cases with ruptured vertebral artery (VA) dissection involving the origin of
      the posterior inferior cerebellar artery (PICA) are presented. Endovascular
      proximal occlusion of the dissected segment proximal to the PICA origin was
      performed, leaving the PICA patent in the acute stage. Stent placement from the
      PICA to the VA through the contralateral VA and coil embolization were added to
      the residual dissection in the chronic stage. Rebleedings were not observed. This
      is the first report of a staged, combined strategy for the treatment of a
      ruptured PICA involving VA dissection, which enabled preservation of the PICA
      without bypass surgery.

PMID- 27038169
TI  - Terson syndrome in aneurysmal subarachnoid hemorrhage-its relation to
      intracranial pressure, admission factors, and clinical outcome.
AB  - BACKGROUND: A large number of reports have not been able to clarify the
      pathophysiology of Terson syndrome (TS) in aneurysmal subarachnoid hemorrhage
      (aSAH). METHODS: Prospective single-center study on aSAH patients. Fundoscopic
      and radiological signs of TS were assessed. The opening intracranial pressure
      (ICP) in patients who required a ventriculostomy was recorded with a manometer.
      RESULTS: Six out of 36 included patients had TS (16.7 %), which was associated
      with unfavorable admission scores. Twenty-nine patients (80.5 %) required
      ventriculostomy; TS was associated with higher ICP (median, 40 vs. 15 cm cmH2O, p
      = .003); all patients with TS had pathological ICP values of >20 cmH2O. Patients
      with a ruptured aneurysm of the anterior cerebral artery complex were ten times
      as likely to suffer from TS (OR 10.0, 95 % CI 1.03-97.50). Detection of TS on CT
      had a sensitivity of 50 %, a specificity of 98.4 %, a positive predictive value
      of 83.3 %, and a negative predictive value of 92.4 %. Mortality was 45 times as
      high in patients with TS (OR 45.0, 95 % CI 3.86-524.7) and neurologic morbidity
      up until 3 months post-aSAH was significantly higher in patients with TS (mRS 4
      6; 100 vs. 17 %; p = .001). CONCLUSIONS: Our findings demonstrate an association
      between raised ICP and the incidence of TS. TS should be ruled out in aSAH
      patients presenting comatose or with raised ICP to ensure upfront
      ophthalmological follow-up. In alert patients without visual complaints and a TS
      negative CT scan, the likelihood for the presence of TS is very low.

PMID- 27038170
TI  - Overexpression and purification of folded domain of prostate cancer related
      proteins MSMB and PSA.
AB  - Overexpression of domains of a human protein using recombinant DNA technology has
      been challenging because individual domains intend to accumulate as non-soluble
      aggregate when expressed separately. Studies on identifying right sequences for a
      domain to be able to fold independently may help understand the folding pattern
      and underlying protein-engineering events to isolate the functional domains of a
      protein. In this report, individual domains of prostate cancer related
      biomarkers; MSMB and PSA were overexpressed in bacterial system and purified in
      their folded forms using affinity chromatography. The western blotting experiment
      using domain specific antibodies further confirmed these proteins. The designed
      nucleotide sequences domains were truncated using fold index software and folding
      were predicted by phyre2 and I-TASSER software. Other parameters were optimized
      for their overexpression and purification using Co-NTA affinity chromatography.
      Purified domains of each protein showed secondary structures such as alpha + beta
      type for PSA, alpha/beta and beta type for the each domains of PSA and MSMB
      respectively. This is the first report on producing PSA and MSMB individual
      domains in functional folded forms. This study may help produce the folded domain
      of many such proteins to be used for better diagnostic purpose.

PMID- 27038171
TI  - Genetic diversity of Guangxi chicken breeds assessed with microsatellites and the
      mitochondrial DNA D-loop region.
AB  - The domestic chicken (Gallus gallus domesticus) is an excellent model for genetic
      studies of phenotypic diversity. The Guangxi Region of China possesses several
      native chicken breeds displaying a broad range of phenotypes well adapted to the
      extreme hot-and-wet environments in the region. We thus evaluated the genetic
      diversity and relationships among six native chicken populations of the Guangxi
      region and also evaluated two commercial breeds (Arbor Acres and Roman chickens).
      We analyzed the sequences of the D-loop region of the mitochondrial DNA (mtDNA)
      and 18 microsatellite loci of 280 blood samples from six Guangxi native chicken
      breeds and from Arbor Acres and Roman chickens, and used the neighbor-joining
      method to construct the phylogenetic tree of these eight breeds. Our results
      showed that the genetic diversity of Guangxi native breeds was relatively rich.
      The phylogenetic tree using the unweighed pair-group method with arithmetic means
      (UPGAM) on microsatellite marks revealed two main clusters. Arbor Acres chicken
      and Roman chicken were in one cluster, while the Guangxi breeds were in the other
      cluster. Moreover, the UPGAM tree of Guangxi native breeds based on
      microsatellite loci was more consistent with the genesis, breeding history,
      differentiation and location than the mtDNA D-loop region. STRUCTURE analysis
      further confirmed the genetic structure of Guangxi native breeds in the Neighbor
      Net dendrogram. The nomenclature of mtDNA sequence polymorphisms suggests that
      the Guangxi native chickens are distributed across four clades, but most of them
      are clustered in two main clades (B and E), with the other haplotypes within the
      clades A and C. The Guangxi native breeds revealed abundant genetic diversity not
      only on microsatellite loci but also on mtDNA D-loop region, and contained
      multiple maternal lineages, including one from China and another from Europe or
      the Middle East. 

PMID- 27038172
TI  - Manganese Oxide Nanorod-Decorated Mesoporous ZSM-5 Composite as a Precious-Metal
      Free Electrode Catalyst for Oxygen Reduction.
AB  - A precious-metal-free cathode catalyst, MnO2 nanorod-decorated mesoporous ZSM-5
      zeolite nanocomposite (MnO2 / m-ZSM-5), has been successfully synthesized by a
      hydrothermal and electrostatic interaction approach for efficient electrochemical
      catalysis of the oxygen reduction reaction (ORR). The active MnOOH species, that
      is, Mn(4+) /Mn(3+) redox couple and Bronsted acid sites on the mesoporous ZSM-5
      matrix facilitate an approximately 4 e(-) process for the catalysis of the ORR
      comparable to commercial 20 wt % Pt/C. Stable electrocatalytic activity with 90 %
      current retention after 5000 cycles, and more importantly, excellent methanol
      tolerance is observed. Synergetic catalytic effects between the MnO2 nanorods and
      the mesoporous ZSM-5 matrix are proposed to account for the high electrochemical
      catalytic performance.

PMID- 27038173
TI  - Dynamic Assessment of Functional Lipidomic Analysis in Human Urine.
AB  - The development of enabling mass spectrometry platforms for the quantification of
      diverse lipid species in human urine is of paramount importance for understanding
      metabolic homeostasis in normal and pathophysiological conditions. Urine
      represents a non-invasive biofluid that can capture distinct differences in an
      individual's physiological status. However, currently there is a lack of
      quantitative workflows to engage in high throughput lipidomic analysis. This
      study describes the development of a MS/MS(ALL) shotgun lipidomic workflow and a
      micro liquid chromatography-high resolution tandem mass spectrometry (LC-MS/MS)
      workflow for urine structural and mediator lipid analysis, respectively. This
      workflow was deployed to understand biofluid sample handling and collection,
      extraction efficiency, and natural human variation over time. Utilization of 0.5
      mL of urine for structural lipidomic analysis resulted in reproducible
      quantification of more than 600 lipid molecular species from over 20 lipid
      classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator
      lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids
      generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In
      summary, the high-throughput functional lipidomics workflow described in this
      study demonstrates an impressive robustness and reproducibility that can be
      utilized for population health and precision medicine applications.

PMID- 27038174
TI  - Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic
      Acid with Combined Intake in Rats.
AB  - Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase
      the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3
      PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on
      the effects of prolonged combined dietary supplementation of DHA and lecithin on
      RBC and plasma PUFA levels. In the current experiments, levels of DHA and
      choline, two dietary ingredients that enhance neuronal membrane formation and
      function, were determined in plasma and red blood cells (RBC) from rats after
      dietary supplementation of DHA-containing oils with and without concomitant
      dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide
      experimental evidence for the hypothesized additive effects of dietary lecithin
      (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC.
      Dietary supplementation of DHA-containing oils, either as vegetable algae oil or
      as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and
      decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin
      supplementation alone did not affect these levels. However, combined dietary
      supplementation of DHA and lecithin increased the changes induced by DHA
      supplementation alone. Animals receiving a lecithin-containing diet also had a
      higher plasma free choline concentration as compared to controls. In conclusion,
      dietary DHA-containing oils and crude lecithin have synergistic effects on
      increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing
      the systemic availability of dietary DHA, dietary lecithin may increase the
      efficacy of DHA supplementation when their intake is combined.

PMID- 27038175
TI  - An Analysis of Complication Risk Factors in 641 Nipple Reconstructions.
AB  - Nipple-areola reconstruction represents the completion of the breast restorative
      process and is associated with significant positive psychological implications.
      While factors such as medical comorbidities, smoking status, and radiation
      therapy have been shown to be associated with an increase in complications
      following breast reconstruction, their impact on nipple reconstruction remains
      largely unaddressed in the literature. An IRB-approved, retrospective review of
      472 patients who underwent nipple reconstruction at Wake Forest University over a
      15-year period was completed. Demographic and surgical characteristics were
      assessed including age, body mass index, medical comorbidities, smoking status,
      need for radiation, breast reconstruction type, and nipple flap used. Four
      hundred and seventy-two patients with 641 nipple reconstructions were included
      with an average follow-up of 56.5 months. Radiation prior to nipple
      reconstruction was required in 146 breasts (22.8%). Overall, postoperative nipple
      projection problems occurred in 7.6% of reconstructions with a 4.1% rate of other
      complications, including nipple necrosis, tip loss, wound infection and wound
      breakdown. Implant-based reconstruction and radiation were associated with
      significantly more nipple projection problems (p = 0.009 and 0.05, respectively).
      Higher rates of complications and nipple projection problems were seen with skate
      flap reconstruction compared to a star flap (p = 0.046 and 0.001, respectively).
      Implant-based breast reconstruction and radiotherapy are associated with higher
      rates of nipple reconstruction problems. Identification of patient and surgical
      variables associated with increased risk of poor outcomes preoperatively could
      help in patient counseling and selection of the most appropriate method of breast
      and nipple reconstruction. 

PMID- 27038180
TI  - Marijuana-derived Delta-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated
      delayed-type hypersensitivity through microRNA regulation.
AB  - ?(9)-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids
      derived from the Cannabis sativa plant and is known for its anti-inflammatory
      properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T
      helper cells including the classic inflammatory Th1 lineage as well as the more
      recently discovered Th17 lineage. In the current study, we investigated whether
      THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH
      response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased
      swelling and infiltration of immune cells at the site of antigen rechallenge.
      Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17
      lineage commitment, including reduced lineage-specific transcription factors and
      cytokines. Interestingly, while DTH caused an overexpression of miR-21, which
      increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR
      29b, an IFN-gamma inhibitor, THC treatment reversed this microRNA (miR)
      dysregulation. Furthermore, when we transfected primary cells from DTH mice with
      miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of
      target gene message was directly impacted increasing SMAD7 and decreasing IFN
      gamma expression, respectively. In summary, the current study suggests that THC
      treatment during DTH response can simultaneously inhibit Th1/Th17 activation via
      regulation of microRNA (miRNA) expression. KEY MESSAGES: * THC treatment inhibits
      simultaneous Th1/Th17 driven inflammation. * THC treatment corrects DTH-mediated
      microRNA dysregulation. * THC treatment regulates proinflammatory cytokines and
      transcription factors.

PMID- 27038181
TI  - Efficient generation of functional pancreatic beta-cells from human induced
      pluripotent stem cells.
AB  - BACKGROUND: Insulin-secreting cells have been generated from human embryonic or
      induced pluripotent stem cells (iPSCs) by mimicking developmental processes.
      However, these cells do not always secrete glucose-responsive insulin, one of the
      most important characteristics of pancreatic beta-cells. We focused on the
      importance of endodermal differentiation from human iPSCs in order to obtain
      functional pancreatic beta-cells. METHODS: A six-stage protocol was established
      for the differentiation of human iPSCs to pancreatic beta-cells using defined
      culture media without feeders or serum. The effects of CHIR99021, a selective
      glycogen synthase kinase-3beta inhibitor, were examined in the presence of
      fibroblast growth factor 2, activin, and bone morphogenetic protein 4 (FAB)
      during definitive endodermal induction by immunostaining for SRY (sex determining
      region Y)-box 17 (SOX17) and Forkhead box protein A2 (FOXA2). Insulin secretion
      was compared between the last stage of monolayer culture and spheroid culture
      conditions. Cultured cells were transplanted under kidney capsules of
      streptozotocin-diabetic non-obese diabetic-severe combined immunodeficiency mice,
      and blood glucose levels were measured once a week. Immunohistochemical analyses
      were performed 4 and 12 weeks after transplantation. RESULTS: Addition of
      CHIR99021 (3 MUmol/L) in the presence of FAB for 2 days improved endodermal cell
      viability, maintaining the high SOX17-positive rate. Spheroid formation after the
      endocrine progenitor stage showed more efficient insulin secretion than did
      monolayer culture. After cell transplantation, diabetic mice had lower blood
      glucose levels, and islet-like structures were detected in vivo. CONCLUSION:
      Functional pancreatic beta-cells were generated from human iPSCs. Induction of
      definitive endoderm and spheroid formation may be key steps for producing these
      cells.

PMID- 27038182
TI  - CLINICAL AND MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF THORACOLUMBAR
      INTERVERTEBRAL DISK EXTRUSIONS AND PROTRUSIONS IN LARGE BREED DOGS.
AB  - Treatment recommendations differ for dogs with intervertebral disk extrusion vs.
      intervertebral disk protrusion. The aim of this retrospective, cross-sectional
      study was to determine whether clinical and magnetic resonance imaging (MRI)
      variables could be used to predict a diagnosis of thoracolumbar intervertebral
      disk extrusion or protrusion in dogs. Dogs were included if they were large breed
      dogs, had an MRI study of the thoracolumbar or lumbar vertebral column, had
      undergone spinal surgery, and had the type of intervertebral disk herniation
      (intervertebral disk extrusion or protrusion) clearly stated in surgical reports.
      A veterinary neurologist unaware of surgical findings reviewed MRI studies and
      recorded number, location, degree of degeneration and morphology of
      intervertebral disks, presence of nuclear clefts, disk space narrowing, extent,
      localization and lateralization of herniated disk material, degree of spinal cord
      compression, intraparenchymal intensity changes, spondylosis deformans, spinal
      cord swelling, spinal cord atrophy, vertebral endplate changes, and presence of
      extradural hemorrhage. Ninety-five dogs were included in the sample.
      Multivariable statistical models indicated that longer duration of clinical signs
      (P = 0.01), midline instead of lateralized disk herniation (P = 0.007), and
      partial instead of complete disk degeneration (P = 0.01) were associated with a
      diagnosis of intervertebral disk protrusion. The presence of a single
      intervertebral herniation (P = 0.023) and dispersed intervertebral disk material
      not confined to the disk space (P = 0.06) made a diagnosis of intervertebral disk
      extrusion more likely. Findings from this study identified one clinical and four
      MRI variables that could potentially facilitate differentiating intervertebral
      disk extrusions from protrusions in dogs. 

PMID- 27038183
TI  - The Effects of Copper on Brain Microvascular Endothelial Cells and Claudin Via
      Apoptosis and Oxidative Stress.
AB  - Many neurodegenerative diseases are related to copper although the effects on
      brain microvascular endothelial cells (BMECs) are poorly understood. In the
      present study, a primary BMEC culture model was established to evaluate the
      effects of copper on brain microvascular endothelial cells and whether claudin-1,
      claudin-3, claudin-5, and claudin-12 isoforms contribute to apoptosis and
      intrinsic antioxidant activity. Our results showed that copper ions had dual
      effects on BMECs by regulating intracellular reactive oxygen species (ROS)
      levels. Copper levels between 30 and 120 MUM could enhance viability and promote
      proliferation. On the other hand, copper cytotoxicity was a result of apoptosis
      indicating a redox-independent manner of cell death. Expression levels of
      claudins were also regulated by copper in a concentration-dependent manner. We
      identified four claudin isoforms (1, 3, 5, and 12) and showed that their
      expression levels were regulated as a group by copper. Antioxidant activity of
      BMECs was also copper regulated, and superoxide dismutase and catalase were the
      main contributors to BMEC antioxidant functions. Together, our results indicated
      that copper had dual effects on BMEC growth and intrinsic antioxidant activities
      played a crucial role in BMEC survival and tight junction.

PMID- 27038184
TI  - Long-Term Supplementation with Chromium Malate Improves Short Chain Fatty Acid
      Content in Sprague-Dawley Rats.
AB  - Our previous study showed that chromium malate improved the composition of
      intestinal flora, glycometabolism, glycometabolism-related enzymes, and lipid
      metabolism in type 2 diabetes mellitus (T2DM) rats. The present study was
      designed to evaluate the effect of chromium malate with long-term supplementation
      on short chain fatty acid (SCFA) content in Sprague-Dawley rats. The samples were
      analyzed by gas chromatography with high linearity (R 2 >= 0.9995), low
      quantification limit (0.011-0.070 mM), and satisfactory recoveries. The method
      was simple and environmentally friendly. The acetic content in cecum of 3-month
      control group was significantly higher than that of 1-year control group. When
      compared with 1-year control group, chromium malate (at a dose of 20.0 MUg Cr/kg
      bw) could significantly increase acetic, propionic, i-butyric butyric, butyric, i
      valeric, valeric, and n-caproic levels. The acetic, propionic, i-butyric,
      valeric, and n-caproic contents of 1-year chromium malate group (at a dose of
      20.0 MUg Cr/kg bw) had a significant improvement when compared with 1-year
      chromium picolinate group. Acetic, propionic, and butyric contained approximately
      91.65 % of the total SCFAs in 1-year group. The results indicated that the
      improvement of chromium malate on short chain fatty acid content change was
      better than that of chromium picolinate.

PMID- 27038185
TI  - The impact of US Government assistance on recidivism.
AB  - BACKGROUND: Community re-entry from custody programmes facilitate access to
      community resources, such as cash assistance and food stamps, with the aim of
      reducing criminal recidivism. Evidence that these programmes achieve is mainly
      from longer-term prisoners rather than short-term jail inmates. AIM: The aim of
      the study is to test the hypothesis that facilitating access to community
      resources while still in jail would reduce re-arrest rates among former jail
      inmates in the USA. METHODS: Community resources offered to the jail inmates
      participating in this study included Medicaid, food stamps and cash assistance.
      Participants who opted to sign up for these social services were matched with non
      applicants based on date of release (n = 101). Each participant's criminal
      history was coded prior to release from the jail and at three months, six months
      and one year after release. RESULTS: Contrary to our original hypotheses,
      recidivism was not significantly reduced in the applicant group. People released
      after facilitated access to community assistance had an increase in drug offence
      severity at six months after release. Recidivism also differed by age and race.
      CONCLUSION: The substance offences in the applicant group suggested that cash
      benefits provided the released offender with the means to sustain their substance
      misuse. Treatment for substance misuse should be incorporated with other
      resources in order to reduce recidivism effectively. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27038186
TI  - Erratum to: Depression, anxiety, and quality of life in a large cohort of
      patients with rheumatic diseases: common, yet undertreated.

PMID- 27038187
TI  - Relative expression and correlation of tumor necrosis factor-alpha, interferon
      gamma, and interleukin-17 in the rheumatoid synovium.
AB  - Although tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma),
      and interleukin-17 (IL-17) play important roles in RA, their relative expression
      and possible correlation in synovial tissues are not well understood. In this
      study, mRNA expression levels of IFN-gamma, IL-17, and TNF-alpha were
      investigated in individual patients with RA and the correlations between pairs of
      these three pro-inflammatory cytokines were analyzed. Synovial tissues were
      obtained during arthroplasties from 24 joints of 24 RA patients. After harvesting
      synovial tissues, total RNA was isolated then quantitative real-time polymerase
      chain reaction (qRT-PCR) for IFN-gamma, IL-17, and TNF-alpha was performed.
      Correlation of expression levels between them was also analyzed. Expression
      levels of TNF-alpha, IFN-gamma, and IL-17 in patients receiving TNF inhibitors
      (TNFi) and those treated with conventional synthetic disease-modifying
      antirheumatic drugs (csDMARDs) alone were also compared between groups. Based on
      relative expression levels of the three pro-inflammatory cytokines, patients were
      classified into three major types; an IFN-gamma plus TNF-alpha-dominant type, an
      IL-17-dominant type, and the other type. TNF-alpha expression levels were
      correlated with IFN-gamma. In addition, there was a negative correlation between
      TNF-alpha and IL-17, and IFN-gamma and IL-17. Median relative expression levels
      of TNF-alpha have no significant difference between the TNFi and the csDMARDs
      groups. In the rheumatoid synovial tissues, expression levels of TNF-alpha were
      modulated in parallel with IFN-gamma, and TNF-alpha and IL-17, or IFN-gamma and
      IL-17 did not co-express at high levels. This characteristic expression pattern
      of the three pro-inflammatory cytokines may be clinically useful information in
      the current cytokine-targeted treatment with biological DMARDs for RA. 

PMID- 27038188
TI  - Histone H3 genotyping refines clinico-radiological diagnostic and prognostic
      criteria in DIPG.

PMID- 27038190
TI  - Thought-shape fusion in young healthy females appears after vivid imagination of
      thin ideals.
AB  - BACKGROUND AND OBJECTIVES: It has been shown that exposure to female thin ideals
      in media has minimal to moderate direct effects on body image satisfaction (BIS),
      mood and dysfunctional eating in healthy young women. Evidence has been found for
      several intervening variables such as social comparison processes. Accordingly it
      is assumed, that cognitive processing (rather than mere media exposure) is
      crucial. Consequently, vivid imagination of thin ideals after exposure to a
      fashion magazine was induced in order to trigger cognitive processes. Changes in
      mood, BIS and resulting bodyrelated cognitive distortions (Thought-Shape Fusion
      Body, TSF-B) were assessed. METHODS: A total of 91 healthy women (mean age 21.9
      years, SD = 2.0) were exposed to either a fashion magazine (thin-ideal group) or
      a nature magazine (control group) in a waiting room design. Afterwards they were
      instructed to vividly imagine either the thin ideals or landscapes. RESULTS: When
      exposed to thin ideals, a significant decrease in mood and BIS emerged after
      vivid imagination, but not after mere magazine exposure. Imagining thin ideals
      triggered body-related cognitive distortions (TSF-B). A higher degree of eating
      disorder (ED) symptomatology amplified this effect. LIMITATIONS: These findings
      apply to young healthy females and cannot be generalized to samples with obesity,
      EDs or males. Internal validity is limited since the intensity of the exposure
      has not been systematically controlled. CONCLUSIONS: Vivid imagination of thin
      ideals promoted by magazines results in impaired mood and BIS and moreover in
      body-related cognitive distortions (TSF-B) in healthy women, especially, for
      those with stronger ED symptomatology.

PMID- 27038191
TI  - Are addiction-related memories malleable by working memory competition? Transient
      effects on memory vividness and nicotine craving in a randomized lab experiment.
AB  - BACKGROUND AND OBJECTIVES: Experimental research suggests that working memory
      (WM) taxation reduces craving momentarily. Using a modified Eye Movement
      Desensitization and Reprocessing (EMDR) procedure, prolonged reductions in
      craving and relapse rates in alcohol dependence have been demonstrated. Modified
      EMDR-procedures may also hold promise in smoking cessation attempts. A proof-of
      concept study was conducted to narrow the gap between WM-taxation experiments and
      clinical EMDR studies. To this end the clinical EMDR-procedure was modified for
      use in a laboratory experiment. METHODS: Daily smokers (n = 47), abstaining
      overnight, were allocated (by minimization randomization) to one of two groups
      using a parallel design. In both cases a modified EMDR-procedure was used. In the
      experimental group (n = 24) eye movements (EM) were induced while control group
      participants (n = 23) fixed their gaze (not taxing WM). During 6 min trials,
      craving-inducing memories were recalled. Craving, vividness of target memories,
      and smoking behavior were assessed at several variable-specific time-points
      between baseline (one week pre-intervention) and one week follow-up. RESULTS: The
      experimental group showed significant immediate reductions of craving and
      vividness of targeted memories. However, these effects were lost during a one
      week follow-up period. CONCLUSIONS: A limited dose of WM-taxation, in the form of
      EM in a modified EMDR-procedure, resulted in transient effects on memory
      vividness and nicotine craving. EM provide a valuable way of coping with the
      acute effects of craving during smoking cessation attempts. Other aspects of the
      EMDR-procedure may provide additional effects. Component and dose-response
      studies are needed to establish the potential of EMDR-therapy in smoking
      cessation.

PMID- 27038189
TI  - Brain imaging of neurovascular dysfunction in Alzheimer's disease.
AB  - Neurovascular dysfunction, including blood-brain barrier (BBB) breakdown and
      cerebral blood flow (CBF) dysregulation and reduction, are increasingly
      recognized to contribute to Alzheimer's disease (AD). The spatial and temporal
      relationships between different pathophysiological events during preclinical
      stages of AD, including cerebrovascular dysfunction and pathology, amyloid and
      tau pathology, and brain structural and functional changes remain, however, still
      unclear. Recent advances in neuroimaging techniques, i.e., magnetic resonance
      imaging (MRI) and positron emission tomography (PET), offer new possibilities to
      understand how the human brain works in health and disease. This includes methods
      to detect subtle regional changes in the cerebrovascular system integrity. Here,
      we focus on the neurovascular imaging techniques to evaluate regional BBB
      permeability (dynamic contrast-enhanced MRI), regional CBF changes (arterial spin
      labeling- and functional-MRI), vascular pathology (structural MRI), and cerebral
      metabolism (PET) in the living human brain, and examine how they can inform about
      neurovascular dysfunction and vascular pathophysiology in dementia and AD.
      Altogether, these neuroimaging approaches will continue to elucidate the spatio
      temporal progression of vascular and neurodegenerative processes in dementia and
      AD and how they relate to each other. 

PMID- 27038192
TI  - The influence of locally applied granulocyte-colony stimulating factor on
      osteoporotic bone.
AB  - OBJECTIVES: The compromised capacity of bone healing in osteoporotic population
      renders a serious concern of patients and clinicians. This study aimed to
      investigate the influence of G-CSF on bone reconstruction using an osteoporotic
      animal model. MATERIALS AND METHODS: Sixty skeletal mature female Spraque-Dawley
      rats underwent bilateral ovariectomy (OVX) and were assigned into three groups (n
      = 20). Three months after OVX, defects of 5 mm in cranial and 2 mm in femur were
      surgically created on all the animals. The defects were left unfilled, filled
      with gelatin sponge (GS), or filled with granulocyte-colony stimulating factor (G
      CSF) infused GS. Specimens were retrieved for histomorphometric and micro-CT
      analyses at weeks 1, 4, 8, and 12 after surgery. RESULTS: At early stage of week
      1 to week 8, the histomorphometric and micro-CT analysis demonstrated more
      advanced bone formation in femur in the control group; by week 12, all groups
      achieved cortical closure. In cranial bone, more advanced bone formation was
      exhibited in G-CSF-treated group at both early and late stages, although this
      observation was not statistically significant. CONCLUSIONS: The results indicated
      that in osteoporotic bone, G-CSF may advance bone healing in cranial bone where
      spontaneous bone formation was insufficient.

PMID- 27038193
TI  - Detection of wide genetic diversity and several novel strains among non-avium
      nontuberculous mycobacteria isolated from farmed and wild animals in Hungary.
AB  - AIMS: Besides Mycobacterium avium numerous nontuberculous Mycobacterium (NTM)
      species exist, which pose constant health risk to both humans and animals. The
      aim of our study was to identify non-avium NTM isolates from veterinary origin in
      Hungary, and to detect the occurrence of rifampicin resistance among them.
      METHODS AND RESULTS: Two hundred and twenty-five strains isolated between 2006
      and 2013 from domestic and wild animals and veterinary important samples were
      identified on the basis of partial DNA sequences of different structural or
      coding genes, besides commercial kits and multiplex PCR. From 14 different
      sources, 28 NTM strains and 8 hitherto unidentified strain types were detected.
      Mycobacterium nonchromogenicum was the most frequently occurring strain (25.78%).
      Besides, new hosts and mycobacteria-related pathological symptoms were detected.
      Noticeable rifampicin resistance (42.76%) was found among 159 strains from six
      different host species. Furthermore, we described the problematics of strain
      misidentifications using commercial kits. CONCLUSIONS: Our study identified the
      most common non-avium NTM strains in Hungary, and provided account of their
      occurrence, host range, and pathogenicity. The detected high rifampicin
      resistance among the strains isolated mainly from fallow and red deer clearly
      shows that more attention should be paid to the examination of wild animals
      especially to those ones which may have contact or shared territory with farmed
      animals. SIGNIFICANCE AND IMPACT OF THE STUDY: In domestic animal husbandry the
      maintenance of tuberculosis free status is of primary importance. As
      immunological cross-reactions due to NTM hamper the diagnosis of bovine
      tuberculosis, the precise identification of NTM strains would be essential in the
      veterinary diagnostics, especially for potentially zoonotic strains. This is the
      first study investigating the strain diversity of non-avium NTM in Hungary.

PMID- 27038194
TI  - The use of FAMACHA in estimation of gastrointestinal nematodes and total worm
      burden in Damara and Barbados Blackbelly cross sheep.
AB  - The prevalence of gastrointestinal (GI) nematodes and total worm burden of Damara
      and Barbados Blackbelly cross sheep was investigated among smallholder farms in
      Salak Tinggi district of Selangor, Malaysia. A total of 50 sheep raised in
      smallholder farms comprising of 27 Damara cross and 23 Barbados Blackbelly cross
      were categorized based on their age into young and adults. Fecal samples were
      collected and examined for strongyle egg count by using modified McMaster
      technique. Severity of infection was categorized into mild, moderate, and heavy,
      based on egg per gram (EPG). Five sheep were randomly selected and slaughtered to
      examine the presence of adult gastrointestinal (GI) nematodes through total worm
      count (TWC). Faffa Malan Chart (FAMACHA) score was used for investigation of worm
      load based on the degree of anemia. The study revealed an overall EPG prevalence
      of 88 %, of which 84.1 % had mild infection. There was a significant difference
      (p = 0.002) in EPG among the two breeds. Based on age, significant difference (p
      = 0. 004) in EPG was observed among Barbados Blackbelly cross, but not for Damara
      cross (p = 0.941). The correlation between severity of infection and the FAMACHA
      score was significant (r = 0.289; p = 0.042). Haemonchus spp. were the most
      predominant nematode found in the gastrointestinal tract, followed by
      Trichostrongylus and Oesophagostomum spps. EPG and TWC for Haemonchus were
      positively correlated, but not significant (r = 0.85, p = 0.066). From regression
      analysis, 73 % of the variability in TWC for Haemonchus could be explained by
      EPG. Thus, it can be concluded that FAMACHA score correlates well with severity
      of infection of a nematode and can be used to assess the strongyle nematode
      burden in the different sheep crosses. 

PMID- 27038195
TI  - The role of herpesviruses (BoHV-1 and BoHV-4) and pestiviruses (BVDV and BDV) in
      ruminant abortion cases in western Turkey.
AB  - The economic impact of abortions in ruminant breeders is one of the biggest
      problems in livestock. Of the infectious agents, viruses, especially
      herpesviruses and pestiviruses, are the most important causative agents of
      abortion in ruminants. In the present study, the role of herpesviruses (bovine
      herpesvirus-1 (BoHV-1), bovine herpesvirus-4 (BoHV-4)) and pestiviruses (bovine
      viral diarrhea virus (BVDV), border disease virus (BDV)) was investigated in
      cases of ruminant abortion between 2007 and 2015 in western Turkey. Out of 81
      aborted fetal samples (60 calves, 19 lambs, and 2 kids), 42 were positive, which
      included 31 calves, 9 lambs, and 2 goats; 39 aborted fetal samples were negative
      for the pestivirus antigen ELISA. BoHV-1 antigen ELISA was positive in 3 cases
      which included 2 calves and 1 lamb; the remainder 78 cases were negative.
      Pestivirus and BoHV-1 were positive in 51.85 and 3.70 %, respectively, of the
      samples. According to PCR analysis, BoHV-4 was not encountered in any of the
      tested samples. In one of the calf fetus samples, both BVDV and BoHV-1 were
      positive; in one of the lamb fetus samples, BoHV-1 was positive. There was a much
      higher level of pestivirus antigen than the other viral agents evaluated in the
      study (p < 0.0001). The results of this study indicate that pestiviruses are a
      common viral cause of ruminant abortions in the examined area. 

PMID- 27038197
TI  - ANZJOG 2016 - Taking up the baton.

PMID- 27038196
TI  - Elastin-like-polypeptide based fusion proteins for osteogenic factor delivery in
      bone healing.
AB  - Modern treatments of bone injuries and diseases are becoming increasingly
      dependent on the usage of growth factors to stimulate bone growth. Bone
      morphogenetic protein-2 (BMP-2), a potent osteogenic inductive protein, exhibits
      promising results in treatment models, but recently has had its practical
      efficacy questioned due to the lack of local retention, ectopic bone formation,
      and potentially lethal inflammation. Where a new delivery technique of the BMP-2
      is necessary, here we demonstrate the viability of an elastin-like peptide (ELP)
      fusion protein containing BMP-2 for delivery of the BMP-2. This fusion protein
      retains the performance characteristics of both the BMP-2 and ELP. The fusion
      protein was found to induce osteogenic differentiation of mesenchymal stem cells
      as evidenced by the production of alkaline phosphatase and extracellular calcium
      deposits in response to treatment by the fusion protein. Retention of the ELPs
      inverse phase transition property has allowed for expression of the fusion
      protein within a bacterial host (such as Escherichia coli) and easy and rapid
      purification using inverse transition cycling. The fusion protein formed self
      aggregating nanoparticles at human-body temperature. The data collected suggests
      the viability of these fusion protein nanoparticles as a dosage-efficient and
      location-precise noncytotoxic delivery vehicle for BMP-2 in bone treatment. (c)
      2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1029-1037,
      2016.

PMID- 27038198
TI  - Is the third trimester repeat ultrasound scan for placental localisation needed
      if the placenta is low lying but clear of the os at the mid-trimester morphology
      scan?

PMID- 27038199
TI  - Unexpected Photo-instability of 2,6-Sulfonamide-Substituted BODIPYs and Its
      Application to Caged GABA.
AB  - Investigation of the unexpected photo-instability of 2,6-sulfonamide-substituted
      derivatives of the boron dipyrromethene (BODIPY) fluorophore led to the discovery
      of a photoreaction accompanied by multiple bond scissions. We characterized the
      photoproducts and utilized the photoreaction to design a caged gamma-aminobutyric
      acid (GABA) derivative that can release GABA upon irradiation in the visible
      range (>450 nm). This allowed us to stimulate neural cells in mouse brain slices.

PMID- 27038201
TI  - 2016 Annual Meeting of the Orthopaedic Research Society Orlando, FL March 5-8,
      2016.
AB  - Searchable abstracts may be found at http://www.ors.org/abstract-search/. 

PMID- 27038200
TI  - A Short History of Automated Office Blood Pressure - 15 Years to SPRINT.

PMID- 27038202
TI  - Reliability of diagnosis from Mohs slides: interpersonal and intrapersonal
      agreement on basal cell carcinoma presence and histological subtype.
AB  - BACKGROUND: The success of Mohs micrographic surgery (MMS) depends partly on the
      correct diagnosis of slides. OBJECTIVES: To determine reliability of diagnosis
      from Mohs slides. METHODS: This was a prospective study evaluating the
      reliability of diagnosis from Mohs slides of basal cell carcinoma (BCC) presence,
      BCC location on the slide and BCC subtype among six raters who independently
      assessed 50 Mohs slides twice with a 2-month interval. Slides were randomly
      selected whereby difficult-to-diagnose slides were oversampled. For each slide, a
      reference diagnosis was established by an expert panel. Cohen's kappa (kappa) was
      calculated to determine levels of agreement interpersonally (rater vs. reference
      diagnosis) and intrapersonally (rater at T1 vs. T2). Multivariable logistic
      regression was used to determine independent risk factors for slides with
      interpersonal discordant diagnosis. The variables studied were BCC presence,
      whether a slide was scored as easy or difficult to diagnose, review duration of
      the 50 slides, profession and years of experience in diagnosis from Mohs slides.
      RESULTS: Interpersonal and intrapersonal agreement were substantial on BCC
      presence (kappa = 0.66 and 0.68) and moderate on BCC subtype (kappa = 0.45 and
      0.55). Slides that were scored as difficult to diagnose were an independent risk
      factor for interpersonal discordant diagnosis on BCC presence (odds ratio 3.54,
      95% confidence interval 1.81-6.84). CONCLUSIONS: Reliability of diagnosis from
      Mohs slides was substantial on BCC presence and moderate on BCC subtype. For
      slides that are scored difficult to diagnose, a second opinion is recommended to
      prevent misinterpretation and thereby recurrence of skin cancer.

PMID- 27038203
TI  - Voluntary action and tactile sensory feedback in the intentional binding effect.
AB  - The intentional binding effect refers to a subjective compression over a temporal
      interval between the start point initialized by a voluntary action and the
      endpoint signaled by an external sensory (visual or audio) feedback. The present
      study aimed to explore the influence of tactile sensory feedback on this binding
      effect by comparing voluntary key-press actions with voluntary key-release
      actions. In experiment 1, each participant was instructed to report the perceived
      interval (in ms) between an action and the subsequent visual sensory feedback. In
      this task, either the action (key-press or key-release) was voluntarily performed
      by the participant or a kinematically identical movement was passively applied to
      the left index finger of the participant. In experiment 2, we explored whether
      the difference in the perception of time was affected by the direction of action.
      In experiment 3, we developed an apparatus in which two parallel laser beams were
      generated by a laser emission unit and detected by a laser receiver unit; this
      allowed the movement of the left index finger to be detected without it touching
      a keyboard (i.e., without any tactile sensory feedback). Convergent results from
      all of the experiments showed that the temporal binding effect was only observed
      when the action was both voluntary and involved physical contact with the key,
      suggesting that the combination of intention and tactile sensory feedback, as a
      form of top-down processing, likely distracted attention from temporal events and
      caused the different binding effects.

PMID- 27038204
TI  - Differences in corticospinal excitability to the biceps brachii between arm
      cycling and tonic contraction are not evident at the immediate onset of movement.
AB  - This is the first study to examine changes in corticospinal excitability to the
      biceps brachii during the onset of arm cycling from a resting position to a point
      when steady-state arm cycling was obtained. Supraspinal and spinal excitability
      were assessed using motor-evoked potentials (MEPs) elicited via transcranial
      magnetic stimulation and cervicomedullary evoked potentials (CMEPs) elicited via
      transmastoid electrical stimulation, respectively. Evoked responses were recorded
      from the biceps brachii during elbow flexion (6 o'clock relative to a clock face)
      for both arm cycling and an intensity-matched tonic contraction at three separate
      periods: (1) immediately at the onset of motor output and after completion of the
      (2) 4th revolution and (3) 9th revolution. There was no difference during
      initiation between tasks for MEP (P = 0.79) or CMEP amplitudes (P = 0.57).
      However, MEP amplitudes were significantly larger during arm cycling than an
      intensity-matched tonic contraction after the completion of the 4th (Cycling
      76.48 +/- 17.35 % of M max, Tonic 63.45 +/- 18.45 % of M max, P < 0.05) and 9th
      revolutions (Cycling 72.37 +/- 15.96 % of M max, Tonic 58.1 +/- 24.23 % of M max,
      P < 0.05). There were no differences between conditions in CMEP amplitudes at the
      4th (Cycling 49.6 +/- 25.4 % of M max, Tonic 41.6 +/- 11.2 % of M max, P = 0.31)
      or the 9th revolution (Cycling 47.2 +/- 17.0 % of M max, Tonic 40.8 +/- 13.6 % of
      M max, P = 0.29). These results demonstrate that corticospinal excitability is
      not different between arm cycling and a tonic contraction at motor output onset,
      but supraspinal excitability is enhanced during steady-state arm cycling. This
      suggests a similarity in the way the corticospinal tract initiates motor outputs
      in humans, regardless of the differences that present themselves in the later,
      steady-state stages.

PMID- 27038205
TI  - Gross primary production controls the subsequent winter CO2 exchange in a boreal
      peatland.
AB  - In high-latitude regions, carbon dioxide (CO2 ) emissions during the winter
      represent an important component of the annual ecosystem carbon budget; however,
      the mechanisms that control the winter CO2 emissions are currently not well
      understood. It has been suggested that substrate availability from soil labile
      carbon pools is a main driver of winter CO2 emissions. In ecosystems that are
      dominated by annual herbaceous plants, much of the biomass produced during the
      summer is likely to contribute to the soil labile carbon pool through litter fall
      and root senescence in the autumn. Thus, the summer carbon uptake in the
      ecosystem may have a significant influence on the subsequent winter CO2
      emissions. To test this hypothesis, we conducted a plot-scale shading experiment
      in a boreal peatland to reduce the gross primary production (GPP) during the
      growing season. At the growing season peak, vascular plant biomass in the shaded
      plots was half that in the control plots. During the subsequent winter, the mean
      CO2 emission rates were 21% lower in the shaded plots than in the control plots.
      In addition, long-term (2001-2012) eddy covariance data from the same site showed
      a strong correlation between the GPP (particularly the late summer and autumn
      GPP) and the subsequent winter net ecosystem CO2 exchange (NEE). In contrast,
      abiotic factors during the winter could not explain the interannual variation in
      the cumulative winter NEE. Our study demonstrates the presence of a cross
      seasonal link between the growing season biotic processes and winter CO2
      emissions, which has important implications for predicting winter CO2 emission
      dynamics in response to future climate change.

PMID- 27038206
TI  - Distribution of antibiotic resistance genes (ARGs) in anaerobic digestion and
      land application of swine wastewater.
AB  - Swine farm and the adjacent farmland are hot spots of ARGs. However, few studies
      have investigated the on-site occurrence of ARGs distributed in the process of
      anaerobic digestion (AD) followed by land application of swine wastewater. Two
      typical swine farms, in southern and northern China respectively, with AD along
      with land application were explored on ARG distributions. ARGs were highly
      abundant in raw swine wastewater, AD effectively reduced the copy number of all
      detected ARGs (0.21-1.34 logs removal), but the relative abundance with different
      resistance mechanisms showed distinctive variation trends. The reduction
      efficiency of ARGs was improved by stable operational temperature and longer
      solid retention time (SRT) of AD. ARGs in soil characterized the contamination
      from the irrigation of the digested liquor. The total ARGs quantity in soil fell
      down by 1.66 logs in idle period of winter compared to application period of
      summer in the northern region, whereas the total amount was steady with whole
      year application in south. Some persistent (sul1 and sul2) and elevated ARGs
      (tetG and ereA) in AD and land application need more attention. 

PMID- 27038207
TI  - A proposal of "core enzyme" bioindicator in long-term Pb-Zn ore pollution areas
      based on topsoil property analysis.
AB  - To study the effects of long-term mining activities on the agricultural soil
      quality of Mengnuo town in Yunnan province, China, the heavy metal and soil
      enzyme activities of soil samples from 47 sites were examined. The results showed
      that long-term mining processes led to point source heavy metal pollution and Pb,
      Cd, Zn and As were the primary metal pollutants. Polyphenoloxidase was found the
      most sensitive soil enzyme activity and significantly correlated with almost all
      the metals (P < 0.05). Amylase (for C cycling), acid phosphatase (for P cycling)
      and catalase (for redox reaction) activities showed significantly positive
      correlations (P < 0.05) with Pb, Cd, Zn and As contents. The correlations between
      soil enzymes activities and Cd, Pb and Zn contents were verified in microcosm
      experiments, it was found that catalase activity had significant correlations (P
      < 0.05) with these three metals in short-term experiments using different soils
      under different conditions. Based on both field investigation and microcosm
      simulation analysis, oxidoreductases activities (rather than a specific enzyme
      activity) were suggested to be used as "core enzyme", which could simply and
      universally indicate the heavy metal pollution degrees of different environments.
      And hydrolases (for C, N, P and S recycling) could be used as a supplement to
      improve correlation accuracy for heavy metal indication in various polluted
      environments. 

PMID- 27038208
TI  - Enantioselective absorption and transformation of a novel chiral neonicotinoid
      [(14)C]-cycloxaprid in rats.
AB  - Neonicotinoid pesticides caused hazardous effects on pollinators and aquatic
      ecosystem. The new developed chiral cis-neonicotinoid cycloxaprid(CYC) is a
      highly potent substitute for low toxicity to bees and high efficiency on target
      insects, but little is known about the metabolic dynamics of racemic CYC and its
      2 enantiomers(SR and RS) in animal models. In this study, chiral separation of
      (14)C-labeled racemic CYC was performed in high-performance liquid chromatography
      under optimal conditions. For the first time that the stereoselectivity of the
      chiral neonicotinoid insecticide CYC was exhibited in rats after single dose oral
      administration using (14)C-labeled isotope trace technique. Enantioselective
      behaviors of racemic CYC, SR and RS were observed in blood metabolism, tissue
      distribution and excretion. The major deposition of (14)C were found in liver,
      lung, kidney and heart. After 24 h, skin and fat showed a strong bioaccumulation
      effect, and total excreted urine and feces of CYC, SR and RS were 50.4%, 59.7%
      and 74.5%, respectively. Enantiomer RS had the fastest absorption and elimination
      rates, and it was least bioaccumulated in rats. The results provide scientific
      basis and practical techniques for environmental risk assessment of chiral
      pesticides, especially neonicotinoids. 

PMID- 27038209
TI  - The binary mixtures of megestrol acetate and 17alpha-ethynylestradiol adversely
      affect zebrafish reproduction.
AB  - Synthetic progesterones and estrogens are broadly used bioactive pharmaceutical
      agents and have been detected in aquatic environments. In the present study, we
      investigated the combined reproductive effects of megestrol acetate (MTA) and
      17alpha-ethinylestradiol (EE2) on zebrafish. Adult zebrafish were exposed to MTA
      (33, 100 or 333 ng/L), EE2 (10 ng/L) or a mixture of both (MTA + EE2: 33 + 10,
      100 + 10 or 333 + 10 ng/L) for 21 days. Results demonstrated that egg production
      was significantly reduced by exposure to 10 ng/L EE2, but not MTA. However, a
      combined exposure to MTA and EE2 caused further reduction of fish fecundity
      compared to EE2 exposure alone, suggesting an additive effect on egg production
      when EE2 is supplemented with MTA. Plasma concentrations of 17beta-estradiol and
      testosterone in the females and 11-ketotestosterone in the males were
      significantly decreased in the groups exposed to EE2 or MTA alone compared with
      the solvent control, and the plasma concentrations of the three hormones were
      further reduced in the co-exposure groups relative to the MTA exposure group, but
      not the EE2 exposure group. These data indicate that the inhibitory effects on
      plasma concentrations in the co-exposures were predominantly caused by EE2.
      Furthermore, exposure to MTA and EE2 (alone or in combination) led to
      histological alterations in the ovaries (decreased vitellogenic/mature oocytes),
      but not in the testes. This study has important implications for environmental
      risk assessment of synthetic hormones that are concurrently present in aquatic
      systems. 

PMID- 27038210
TI  - Mercury species, selenium, metallothioneins and glutathione in two dolphins from
      the southeastern Brazilian coast: Mercury detoxification and physiological
      differences in diving capacity.
AB  - In the present study, the concentration of trace elements, total mercury (Hg) and
      selenium (Se) and mercury forms (MeHg, Hginorg and HgSe) in the vulnerable
      coastal dolphins Pontoporia blainvillei and Sotalia guianensis were appraised and
      compared, using metallothioneins (MT) and glutathione (GSH) as biomarkers for
      trace element exposure. The trace element concentrations varied between muscle
      and liver tissues, with liver of all dolphin specimens showing higher Hg and Se
      concentrations than those found in muscle. Hg, MeHg and Hginorg molar
      concentrations showed a clear increase with Se molar concentrations in the liver
      of both dolphins, and Se concentrations were higher than those of Hg on a molar
      basis. Se plays a relevant role in the detoxification of MeHg in the hepatic
      tissue of both dolphins, forming Hg-Se amorphous crystals in liver. In contrast,
      MT were involved in the detoxification process of Hginorg in liver. GSH levels in
      P. blainvillei and S. guianensis muscle tissue suggest that these dolphins have
      different diving capacities. Muscle Hg concentrations were associated to this
      tripeptide, which protects dolphin cells against Hg stress. 

PMID- 27038211
TI  - Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo.
AB  - Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been
      pointed out of potentially causing developmental neurotoxicity, but the exact
      mechanism is little known. In this study, zebrafish embryos were exposed to 0,
      0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused
      serious hatching delay and body length decrease. The content of MCLR in zebrafish
      larvae was analyzed and the results demonstrated that MCLR can accumulate in
      zebrafish larvae. The locomotor speed of zebrafish larvae was decreased.
      Furthermore, the dopamine and acetylcholine (ACh) content were detected to be
      significantly decreased in MCLR exposure groups. And the acetylcholinesterase
      (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L
      MCLR. The transcription pattern of manf, chrnalpha7 and ache gene was consistent
      with the change of the dopamine content, ACh content and AChE activity. Gene
      expression involved in the development of neurons was also measured. alpha1
      tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene
      expression were observed to be significantly up-regulated upon exposure to MCLR.
      The above results indicated that MCLR-induced developmental toxicity might
      attribute to the disorder of cholinergic system, dopaminergic signaling, and the
      development of neurons. 

PMID- 27038212
TI  - Facile synthesis of (55)Fe-labeled well-dispersible hematite nanoparticles for
      bioaccumulation studies in nanotoxicology.
AB  - Although water-dispersible engineered nanoparticles (ENPs) have a wide range of
      applications, the ENPs used in many nanotoxicological studies tend to form micron
      sized aggregates in the exposure media and thus cannot reflect the toxicity of
      real nanoparticles. Here we described the synthesis of bare hematite
      nanoparticles (HNPs-0) and two poly(acrylic acid) (PAA)-coated forms (HNPs-1 and
      HNPs-2). All three HNPs were well dispersed in deionized water, but HNPs-0
      quickly aggregated in the three culture media tested. By contrast, the
      suspensions of HNPs-1 and HNPs-2 remained stable, with negligible amounts of PAA
      and Fe(3+) liberated from either one under the investigated conditions. To better
      quantify the accumulation of the coated HNPs, a relatively innocuous (55)Fe
      labeled form of HNPs-2 was synthesized as an example and its accumulation in
      three phytoplankton species was tested. Consistent with the uptake kinetics model
      for conventional pollutants, the cellular accumulation of HNPs-2 increased
      linearly with exposure time for two of the three phytoplankton species. These
      results demonstrate the utility of (55)Fe-labeled well-dispersible HNPs as a
      model material for nanoparticle bioaccumulation studies in nanotoxicology. 

PMID- 27038213
TI  - Biological impact of environmental polycyclic aromatic hydrocarbons (ePAHs) as
      endocrine disruptors.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are often detected in the environment and
      are regarded as endocrine disruptors. We here designated mixtures of PAHs in the
      environment as environmental PAHs (ePAHs) to discuss their effects collectively,
      which could be different from the sum of the constituent PAHs. We first
      summarized the biological impact of environmental PAHs (ePAHs) found in the
      atmosphere, sediments, soils, and water as a result of human activities,
      accidents, or natural phenomena. ePAHs are characterized by their sources and
      forms, followed by their biological effects and social impact, and bioassays that
      are used to investigate their biological effects. The findings of the bioassays
      have demonstrated that ePAHs have the ability to affect the endocrine systems of
      humans and animals. The pathways that mediate cell signaling for the endocrine
      disruptions induced by ePAHs and PAHs have also been summarized in order to
      obtain a clearer understanding of the mechanisms responsible for these effects
      without animal tests; they include specific signaling pathways (MAPK and other
      signaling pathways), regulatory mechanisms (chromatin/epigenetic regulation, cell
      cycle/DNA damage control, and cytoskeletal/adhesion regulation), and cell
      functions (apoptosis, autophagy, immune responses/inflammation, neurological
      responses, and development/differentiation) induced by specific PAHs, such as
      benz[a]anthracene, benzo[a]pyrene, benz[l]aceanthrylene, cyclopenta[c,d]pyrene,
      7,12-dimethylbenz[a]anthracene, fluoranthene, fluorene, 3-methylcholanthrene,
      perylene, phenanthrene, and pyrene as well as their derivatives. Estrogen
      signaling is one of the most studied pathways associated with the endocrine
      disrupting activities of PAHs, and involves estrogen receptors and aryl
      hydrocarbon receptors. However, some of the actions of PAHs are contradictory,
      complex, and unexplainable. Although several possibilities have been suggested,
      such as direct interactions between PAHs and receptors and the suppression of
      their activities through other pathways, the mechanisms underlying the activities
      of PAHs remain unclear. Thus, standardized assay protocols for pathway-based
      assessments are considered to be important to overcome these issues. 

PMID- 27038214
TI  - HLA-C*18:01: A Rare Allele in the European Caucasian Population Coinciding with
      Difficult-to-Treat Plaque Psoriasis.
AB  - BACKGROUND: Advances in knowledge about the metabolic pathways involved in the
      pathogenesis of psoriasis and related diseases have led to a search for new
      therapeutic targets and the development of new biological drugs. Several studies
      have focused on HLA-C*06 and investigated correlations between the genetic risk
      factors of psoriasis and clinical parameters such as the severity of the disease
      and the response to treatment. OBJECTIVE: Our objective is to share experience
      from our institution in the observation of two patients with severe chronic
      plaque psoriasis who were unresponsive to any anti-TNF-alpha treatment and only
      partially responsive to ustekinumab. The patients are carriers of a rare allele
      of HLA-C that occurs in Caucasians. METHODS: The patients with moderate-to-severe
      chronic plaque psoriasis, and candidates for biological therapy were typed for
      the HLA-C locus at high resolution via polymerase chain reaction sequence
      specific oligonucleotide probes (PCR-SSOP) using a commercial kit (LAB((r))Type,
      One Lambda Inc., Canoga Park, CA, USA). The socio-demographic variables and
      clinical data were collected. RESULTS: In our cohort of 134 patients, only two
      showed the presence of the allele HLA-C*18:01. To our knowledge, a coincidence
      between HLA-C*18 and severe psoriasis in Caucasian patients has not previously
      been described. The fact that both of these patients showed the same clinical
      history (unresponsive to any anti-TNF-alpha treatment and partially responsive to
      ustekinumab) cannot be attributed to a random observation because HLA-C*18 is
      extremely rare in Europe. As a consequence, at this latitude, it probably
      indicates a severe disease for which the proper therapy has still not been
      identified.

PMID- 27038216
TI  - Genetic background and environmental conditions drive metabolic variation in wild
      type and transgenic soybean (Glycine max) seeds.
AB  - The metabolic profiles and composition of storage reserves of agricultural crop
      seeds are strongly regulated by heritable and environmental factors. Yet, very
      little is known about the genetic and environmental determinants of adaptive
      metabolic variation amongst wild type as well as transgenic seed populations
      derived from the same genetic background, grown under natural field conditions.
      The goal of the current study was to investigate the effects of natural
      environmental conditions on wild type and transgenic soybean seeds expressing a
      feedback-insensitive form of cystathionine gamma-synthase, a methionine main
      regulatory enzyme. The seeds were grown in four geographically distinct habitats
      in China and then assayed for primary metabolic profiles using gas chromatography
      mass spectrometry, morphological traits and storage reserve accumulation. The
      analyses revealed changes in the levels of primary metabolites which evidently
      exhibited high correlation to methionine regardless of changes in environmental
      conditions. The environment, however, constituted a major determinant of
      metabolic profiles amongst seeds, as much more metabolites were observed to be
      affected by this variable, particularly along the north-to-south latitudinal
      gradient. The observations suggest that metabolic variation amongst seeds grown
      under natural field conditions depends upon the complex relationships existing
      amongst their genetic background and the environmental conditions characterizing
      their cultivation areas.

PMID- 27038217
TI  - In vitro characterization of MG-63 osteoblast-like cells cultured on organic
      inorganic lyophilized gelatin sponges for early bone healing.
AB  - The development of three-dimensional porous scaffolds with enhanced osteogenic
      and angiogenic potential would be beneficial for inducing early-stage bone
      regeneration. Previous studies have demonstrated the advantages of mineralized
      and nonmineralized acellular 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide
      hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich
      in growth factors, hydroxyapatite, and chitin whiskers. In this study, those same
      scaffolds were mineralized and dynamically seeded with MG-63 cells. Cell
      proliferation, protein/cytokine secretion, and compressive mechanical properties
      of scaffolds were evaluated. It was found that mineralization and the addition of
      growth factors increased cell proliferation compared to gelatin controls. Cells
      on all scaffolds responded in an appropriate bone regenerative fashion as shown
      through osteocalcin secretion and little to no secretion of bone resorbing
      markers. However, compressive mechanical properties of cellularized scaffolds
      were not significantly different from acellular scaffolds. The combined results
      of increased cellular attachment, infiltration, and bone regenerative
      protein/cytokine secretion on scaffolds support the need for the addition of a
      bone-like mineral surface. Cellularized scaffolds containing growth factors
      reported similar advantages and mechanical values in the range of native tissues
      present in the early stages of bone healing. These results suggest that the
      developed composite sponges exhibited cellular responses and mechanical
      properties appropriate for promoting early bone healing in various applications.
      (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2011-2019,
      2016.

PMID- 27038218
TI  - Territorial and land-use rights perspectives on human-chimpanzee-elephant
      coexistence in West Africa (Guinea, Guinea-Bissau, Senegal, nineteenth to twenty
      first centuries).
AB  - The first part of this article compares the distribution of chimpanzee and
      elephant populations in reaction to human territorial dynamics of West African
      trade in parts of nineteenth century Guinea, Guinea-Bissau and Senegal. It
      answers for this specific region the question of whether present-day situations
      of close chimpanzee-human spatial proximity are stable or only temporary
      phenomena in long-term processes of environmental change, and shows that
      conservation policies centred on either of these two "flagship" species carry
      radically different ecological, political and territorial implications. The
      second part shifts to local-level perspectives on human-chimpanzee relationships,
      emphasizing the land rights contentions and misunderstandings created by the
      implementation of protected areas at Bossou and in the Boke region of Guinea.
      These case studies help to look at acts of resistance and local interpretations
      of primate conservation policies as opportunities to reconsider what is being
      protected, for what purpose, as whose heritage, and to move towards new and more
      legitimate opportunities for the implementation of conservation policies. 

PMID- 27038219
TI  - Iron overload, G6PD deficiency, and lead levels on blood smears.

PMID- 27038220
TI  - Risky drinking behaviors among women with eating disorders-A longitudinal
      community-based study.
AB  - OBJECTIVE: Eating disorders and alcohol use disorders often co-occur, but few
      prospective studies have examined their relationship. Using a large population
      based twin sample, we investigated how the drinking behaviors of women with
      lifetime eating disorders unfold from adolescence to adulthood. METHOD: We
      identified 182 women with a lifetime eating disorder assessed at mean age 24,
      including 92 women with DSM-5 anorexia nervosa and 58 women with DSM-5 bulimia
      nervosa, from the 1975-1979 birth cohorts of Finnish twins (N = 2,825 women).
      Frequency of drinking and intoxicating were assessed at ages 16, 24, and 34.
      Drinking problems were assessed at ages 24 and 34 by the Malmo-modified Michigan
      Alcohol Screening Test (Mm-Mast) and the Rutgers Alcohol Problem Index (RAPI).
      RESULTS: At age 16, proportionately more women with eating disorders reported
      being severely intoxicated when they last drank (25% vs.16%, P = 0.001), and at
      both surveys in adulthood, they reported more frequent intoxication and more
      alcohol-related problems than their unaffected peers. Those who had recovered
      from their eating disorder at age 24 still reported more alcohol-related problems
      in their 30s than did other women. The age of drinking onset, number of monthly
      drinking days, or frequency of intoxication in adolescence did not differ between
      women with lifetime eating disorders and unaffected women. DISCUSSION: Women with
      eating disorders scored higher than their unaffected peers on scales measuring
      alcohol dependence, alcohol-related problems, and intoxication. These differences
      persisted from mid-adolescence into young adulthood. Women with eating disorders
      should be assessed routinely for drinking behaviors. (c) 2016 Wiley Periodicals,
      Inc. (Int J Eat Disord 2016; 49:563-571).

PMID- 27038221
TI  - The Dynamic Organic/Inorganic Interface of Colloidal PbS Quantum Dots.
AB  - Colloidal quantum dots are composed of nanometer-sized crystallites of inorganic
      semiconductor materials bearing organic molecules at their surface. The
      organic/inorganic interface markedly affects forms and functions of the quantum
      dots, therefore its description and control are important for effective
      application. Herein we demonstrate that archetypal colloidal PbS quantum dots
      adapt their interface to the surroundings, thus existing in solution phase as
      equilibrium mixtures with their (metal-)organic ligand and inorganic core
      components. The interfacial equilibria are dictated by solvent polarity and
      concentration, show striking size dependence (leading to more stable ligand/core
      adducts for larger quantum dots), and selectively involve nanocrystal facets.
      This notion of ligand/core dynamic equilibrium may open novel synthetic paths and
      refined nanocrystal surface-chemistry strategies.

PMID- 27038222
TI  - What is new in nanoparticle-based photoacoustic imaging?
AB  - Photoacoustic imaging combines the high temporal and spatial resolution of
      ultrasound with the good contrast and spectral tuning of optical imaging.
      Contrast agents are used in photoacoustic imaging to further increase the
      contrast and specificity of imaging or to image a specific molecular process,
      e.g., cell-surface proteins or small molecule biomarkers. Nanoparticle-based
      contrast agents are important tools in photoacoustic imaging because they offer
      intense and stable signal and can be targeted to specific molecular processes. In
      this review, we describe some of the most interesting and recent advances in
      nanoparticle-based photoacoustic imaging including inorganic nanoparticles,
      organic/polymeric nanoparticles, nanoparticle coatings, multimodality imaging, as
      well as emerging topics in the field. WIREs Nanomed Nanobiotechnol 2017, 9:e1404.
      doi: 10.1002/wnan.1404 For further resources related to this article, please
      visit the WIREs website.

PMID- 27038223
TI  - Conformational flexibility of aspartame.
AB  - L-Aspartyl-L-phenylalanine methyl ester, better known as aspartame, is not only
      one of the most used artificial sweeteners, but also a very interesting molecule
      with respect to the correlation between molecular structure and taste. The
      extreme conformational flexibility of this dipeptide posed a huge difficulty when
      researchers tried to use it as a lead compound to design new sweeteners. In
      particular, it was difficult to take advantage of its molecular model as a mold
      to infer the shape of the, then unknown, active site of the sweet taste receptor.
      Here, we follow the story of the 3D structural aspects of aspartame from early
      conformational studies to recent docking into homology models of the receptor.
      (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376-384, 2016. 

PMID- 27038224
TI  - Topography of claustrum and insula projections to medial prefrontal and anterior
      cingulate cortices of the common marmoset (Callithrix jacchus).
AB  - The claustrum has been the subject of intense research interest in recent years,
      driven in large part by its extensive connections with various regions of the
      cerebral cortex and by hypotheses surrounding its possible role in multimodal
      sensory and/or sensory-emotional integration. Here we employed neuroanatomical
      tracers to map projections from the claustrum-insular region to the medial
      prefrontal and anterior cingulate cortex of the common marmoset (Callithrx
      jacchus). These areas were selected based on their identification as "hub" areas
      of the default mode and cortical salience networks, respectively. Microinjections
      of fluorescent tracers, along with gold-nanoparticle-conjugated cholera toxin B
      subunit and biotinylated dextran amine, were placed in subdivisions of the
      anterior cingulate area 24b/c and in medial prefrontal areas 32 and 32V. The
      resulting distribution of transported label showed rostral-caudal and dorsal
      ventral topographic arrangement of claustrum connections and clear rostral-caudal
      topography of insular projections. Medial prefrontal connections were restricted
      mainly to a ventromedial strip located in the rostral half of the claustrum, with
      a second, smaller patch of cells in the caudal, ventrolateral portion. In
      contrast, injections into area 24 yielded dense, widespread connections from the
      dorsal claustrum, extending along its entire rostral-caudal length. Projections
      from the "classical" agranular, disgranular, and granular insular areas were
      sparse or nonexistent in areas 32 and 32V, with progressively increasing
      connections observed in more caudal tracer injections (i.e., in subdivisions of
      area 24). Transported label was observed in rostral peri-insular areas orbital
      periallocortex, orbital proisocortex, and insular proisocortex following all
      prefrontal injections. These data provide a structural connectivity foundation
      for interpretation of functional imaging studies, which often indicate activity
      in the "anterior insula" that may arise, in part, from claustrum and/or peri
      insular projections to the anterior cingulate and medial prefrontal cortices. J.
      Comp. Neurol. 525:1421-1441, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038225
TI  - Acute p-synephrine ingestion increases fat oxidation rate during exercise.
AB  - AIMS: p-Synephrine is a protoalkaloid widely used in dietary supplements for
      weight management because of its purported thermogenic effects. However, there is
      a lack of scientific information about its effectiveness to increase fat
      metabolism during exercise. The purpose of this investigation was to determine
      the effects of an acute ingestion of p-synephrine on fat oxidation at rest and
      during exercise. METHODS: In a double-blind, randomized and counterbalanced
      experimental design, 18 healthy subjects performed two acute experimental trials
      after the ingestion of p-synephrine (3 mg kg(-1) ) or after the ingestion of a
      placebo (cellulose). Energy expenditure and fat oxidation rates were measured by
      indirect calorimetry at rest and during a cycle ergometer ramp exercise test
      (increases of 25 W every 3 min) until volitional fatigue. RESULTS: In comparison
      with the placebo, the ingestion of p-synephrine did not change energy consumption
      (1.6 +/- 0.3 vs. 1.6 +/- 0.3 kcal min(-1) ; P = 0.69) or fat oxidation rate at
      rest (0.08 +/- 0.02 vs. 0.10 +/- 0.04 g min(-1) ; P = 0.15). However, the intake
      of p-synephrine moved the fat oxidation-exercise intensity curve upwards during
      the incremental exercise (P < 0.05) without affecting energy expenditure.
      Moreover, p-synephrine increased maximal fat oxidation rate (0.29 +/- 0.15 vs.
      0.40 +/- 0.18 g min(-1) ; P = 0.01) during exercise although it did not affect
      the intensity at which maximal fat oxidation was achieved (55.8 +/- 7.7 vs. 56.7
      +/- 8.2% VO2peak ; P = 0.51). CONCLUSIONS: The acute ingestion of p-synephrine
      increased the fat oxidation rate while it reduced the carbohydrate oxidation rate
      when exercising at low-to-moderate exercise intensities.

PMID- 27038226
TI  - Effect of desensitizing agents on the microtensile bond strength of two-step etch
      and-rinse adhesives to dentin.
AB  - Desensitizers can be used to control postoperative sensitivity in adhesive
      restorations. The aim of this study was to evaluate the effect of desensitizing
      agents on the bond strength of two-step etch-and-rinse adhesive systems to
      dentin. Forty-two human molars were sectioned to obtain 3-mm-thick dentin discs.
      The discs were divided into three groups (n = 14 in each) - no-treatment control
      group (CT), and oxalic acid [BisBlock (BB)] and calcium phosphate [Desensibilize
      Nano-P (NP)] desensitizers - before the application of two adhesive systems
      [Adper Single Bond Plus (SB) and One-Step Plus (OSP)]. A nanoparticle composite
      resin was used to create a 3-mm-thick build-up. The specimens were stored in
      distilled water for 24 h before a microtensile bond-strength test was performed.
      The failure modes were determined using a stereomicroscope at 100 *
      magnification. Specimens were sectioned perpendicular to the interface for
      scanning electron microscopy analyses. The CT-SB group exhibited the highest bond
      strength, differing significantly from BB-SB and BB-OSP groups. Mixed failures
      were prevalent for all groups. Scanning electron microscopy revealed a continuous
      hybrid layer and resin tags in all groups. Dentin bond strength of etch-and-rinse
      adhesive systems was reduced by an oxalic acid desensitizer but was not affected
      by a calcium phosphate-containing desensitizer.

PMID- 27038227
TI  - Intraprocedural assessment of mitral regurgitation during the mitraclip
      procedure: Impact of continuous left atrial pressure monitoring.
AB  - INTRODUCTION: Intraprocedural assessment of mitral regurgitation (MR) is a
      challenging issue during the MitraClip procedure, which might influence not only
      the position but also the number of MitraClips implanted. Though transesophageal
      echocardiography (TEE) is the predominant tool used during the MitraClip
      procedure, MR assessment might be facilitated by a multimodality approach
      including continuous and simultaneous determination of left atrial and left
      ventricular (LV) pressure. METHODS: 86 consecutive patients (76.5 +/- 8 years)
      who qualified for the MitraClip procedure were included into the study. In all
      patients, the multimodal assessment of MR (TEE, LV angiogram, TEE bubble
      evaluation, left atrial (LA) pressure => MitraScore) was performed after
      introducing the MitraClip guide catheter. In the first 42 patients (group A, no
      CAP), left atrial (LA) pressure (peak pressure of V-wave) was determined only
      before and after MitraClip implantation, whereas, in the subsequent 44 patients
      (group B, with CAP), continuous left atrial pressure monitoring (CAP) was
      performed. RESULTS: Patients with CAP (group B) had similar total procedural
      durations and no increase in the complication rate. MitraScore decreased from
      10.5 to 3.5 in group A compared to 10.7 to *2.8 in group B (*P = 0.021 vs. group
      B). Whether the significant improvement of intraprocedural MR in group B
      translated into superior MR reduction in the conscious patient, was analyzed by
      transthoracic echocardiography (TTE) in a blinded fashion. Again MR reduction was
      significantly greater (P = 0.03) in group B (MR grade 2.8 to 0.9) as compared to
      group A (MR grade 2.8 to 1.3) and 2D vena contracta decreased from 0.54 +/- 0.15
      cm to 0.17 +/- 0.10 in group B compared to group A (0.56 +/- 0.19 cm to *0.23 +/-
      0.12; *P = 0.01 vs. group B). CONCLUSIONS: Multimodality assessment of
      intraprocedural MR supported by continuous left atrial pressure monitoring was
      associated with superior intraprocedural results translating into improved MR
      reduction also at the end of the hospital stay. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038228
TI  - Risk factors for residual disease after cervical conization in patients with
      cervical intraepithelial neoplasia grades 2 and 3 and positive surgical margins.
AB  - OBJECTIVE: To evaluate risk factors for the persistence of cervical
      intraepithelial neoplasia (CIN) grade >=2 following repeat surgical procedures in
      patients with CIN grades 2 and 3 and positive surgical margins. STUDY DESIGN:
      This study included patients with CIN grades 2 and 3 and positive surgical
      margins following loop electrosurgical excision procedures (LEEP), who had
      undergone additional surgery between 2007 and 2014. Factors associated with CIN
      grade >=2 on biopsy results after the second operation were assessed by multiple
      logistic regression analysis. Factors considered included patient age, parity,
      menopausal status, smoking, referral cytology, initial LEEP pathology, time
      interval between LEEP and surgical procedures, presence of disease on
      endocervical sampling, endocervical surgical margins, glands, disease surrounding
      >=50% of the cervical circumference and requirement for multiple sweeps on
      initial LEEP to excise a lesion. The forward likelihood ratio method was used and
      significance was set at p<0.05. RESULTS: Repeat surgical procedures were
      performed in 104 patients, 75 with CIN 2 and 29 with CIN 3, with 43 (41.3%)
      reported as normal or CIN 1. However, 57 (54.8%) patients had CIN >=2 lesions and
      four (3.8%) had previously undiagnosed cervical cancer. Factors associated with
      CIN >=2 lesions included requirement for multiple sweeps (vs. a single sweep;
      odds ratio [OR] 5.967; 95% confidence interval [CI] 2.183-16.311, p<0.001) and
      involvement of >=50% of the cervical circumference (vs. <50%; OR 5.073; 95% CI
      1.501-17.146, p=0.009). CONCLUSION: As lesions requiring multiple sweeps for
      excision and/or surrounding >=50% of the cervical circumference during initial
      conization are associated with recurrent CIN >=2 lesions, attention should be
      paid during resection to prevent margin positivity. If surgical margins are
      positive, however, repeat surgical procedures should be considered in patients
      with CIN 2 and CIN 3 lesions and these risk factors.

PMID- 27038229
TI  - Rice bacterial endophytes: isolation of a collection, identification of
      beneficial strains and microbiome analysis.
AB  - Endophytes are harmless or beneficial microorganisms that live inside plants
      between cells. The relationship they develop with the plant as well as their
      potential role in plant health is at large unexplored and it is believed that the
      opportunity to find new and interesting endophytes among the large variety of
      plants is great. Here, we present the isolation and analysis of a large
      collection of endophytes from one cultivar of rice grown in Italy. A total 1318
      putative endophytes were isolated from roots, leaves and stems from rice grown in
      submerged and dry conditions and a working collection of 229 isolates was
      created. Among these, several isolates were confirmed to be endophytes and a few
      displayed the trait of plant growth promotion. A cultivation independent analysis
      via 16S rDNA amplicons of the bacterial community of the endosphere was also
      performed providing information on bacterial diversity in the rice endopshere.

PMID- 27038230
TI  - Biochemical and histopathologic analysis of the effects of periodontitis on left
      ventricular heart tissues of rats.
AB  - BACKGROUND AND OBJECTIVE: Current epidemiological works have suggested that
      chronic infections, such as periodontitis, are associated with an increased risk
      of cardiovascular diseases, including hypertrophy and heart failure. However,
      mechanisms behind the association are not known. The aim of this study was to
      evaluate the effects of periodontitis on the serum lipid levels, inflammatory
      marker levels and left ventricular heart muscle tissues of rats. MATERIAL AND
      METHODS: Eighteen male Sprague-Dawley rats were randomly divided into two groups:
      control (without ligature) and experimental periodontitis (EP; ligatured).
      Periodontitis was induced by placing ligatures (3.0 silk) at a submarginal
      position of the lower first molar teeth for 5 wk. Serum samples were collected
      for biochemical studies (C-reactive protein, interleukin-1beta, tumor necrosis
      factor-alpha and serum lipids), after which the rats were killed and heart tissue
      samples were obtained for histopathological and immunological studies (nuclear
      factor kappa B and beta-myosin heavy chain). RESULTS: Significant increases in C
      reactive protein and interleukin-1beta levels and no statistically significant
      increase in tumor necrosis factor-alpha level were observed in the EP group
      compared to the control group. In addition, total cholesterol, low-density
      lipoprotein cholesterol and triglyceride levels were significantly higher in the
      EP group. Stereological and immunological findings showed that the number of
      nuclear factor kappa B-p65- and beta-myosin heavy chain-positive cardiomyocytes
      increased significantly in the left ventricular tissue samples of the rats with
      periodontitis. CONCLUSION: Early chronic phase effects of periodontitis on heart
      tissue are in the form of degenerative and hypotrophic changes. Prolonging the
      exposure to systemic inflammatory stress may increase the risk of occurrence of
      hypertrophic changes.

PMID- 27038231
TI  - PD-1 blockade: a therapeutic option for treatment of metastatic Merkel cell
      carcinoma.
AB  - The immune system is extremely important in the development and progression of
      Merkel cell carcinoma (MCC). Immune checkpoint blockade has recently been shown
      to enable efficacious treatment of a variety of tumours. We report the use of an
      anti-programmed death receptor 1 (PD-1) antibody for treatment of a patient with
      metastatic MCC. An 80-year-old patient with metastatic MCC received off-label
      treatment with the anti-PD-1 antibody pembrolizumab after the disease had
      progressed during therapy with oral etoposide. A positron emission tomography
      (PET) computed tomography scan performed after three cycles of pembrolizumab
      revealed responses to therapy with reduced size of the adrenal gland metastases
      and less PET activity in the adrenal gland and lymph node metastases. Treatment
      was resumed owing to disease progression after a treatment-free interval of > 4
      months. During subsequent months of treatment, the size of the metastases
      stabilized and uptake of nuclide by all tumour sites once again decreased. These
      results reveal the potential efficacy of an anti-PD-1 antibody for treatment of
      metastatic MCC. Thus, they contribute to currently limited data on the use of
      anti-PD-1 antibodies for the treatment of MCC. Moreover, this is the first report
      of successful resumption of treatment of metastatic MCC with an anti-PD-1
      antibody. Results from ongoing trials will contribute to determination of the
      relevance of PD-1 blockade in metastatic MCC.

PMID- 27038232
TI  - Properties and dynamics of inhibitory synaptic communication within the CA3
      microcircuits of pyramidal cells and interneurons expressing parvalbumin or
      cholecystokinin.
AB  - KEY POINTS: To understand how a network operates, its elements must be identified
      and characterized, and the interactions of the elements need to be studied in
      detail. In the present study, we describe quantitatively the connectivity of two
      classes of inhibitory neurons in the hippocampal CA3 area (parvalbumin-positive
      and cholecystokinin-positive interneurons), a key region for the generation of
      behaviourally relevant synchronous activity patterns. We describe how
      interactions among these inhibitory cells and their local excitatory target
      neurons evolve over the course of physiological and pathological activity
      patterns. The results of the present study enable the construction of precise
      neuronal network models that may help us understand how network dynamics is
      generated and how it can underlie information processing and pathological
      conditions in the brain. We show how inhibitory dynamics between parvalbumin
      positive basket cells and pyramidal cells could contribute to sharp wave-ripple
      generation. ABSTRACT: Different hippocampal activity patterns are determined
      primarily by the interaction of excitatory cells and different types of
      interneurons. To understand the mechanisms underlying the generation of different
      network dynamics, the properties of synaptic transmission need to be uncovered.
      Perisomatic inhibition is critical for the generation of sharp wave-ripples,
      gamma oscillations and pathological epileptic activities. Therefore, we aimed to
      quantitatively and systematically characterize the temporal properties of the
      synaptic transmission between perisomatic inhibitory neurons and pyramidal cells
      in the CA3 area of mouse hippocampal slices, using action potential patterns
      recorded during physiological and pathological network states. Parvalbumin
      positive (PV+) and cholecystokinin-positive (CCK+) interneurons showed distinct
      intrinsic physiological features. Interneurons of the same type formed
      reciprocally connected subnetworks, whereas the connectivity between interneuron
      classes was sparse. The characteristics of unitary interactions depended on the
      identity of both synaptic partners, whereas the short-term plasticity of synaptic
      transmission depended mainly on the presynaptic cell type. PV+ interneurons
      showed frequency-dependent depression, whereas more complex dynamics
      characterized the output of CCK+ interneurons. We quantitatively captured the
      dynamics of transmission at these different types of connection with simple
      mathematical models, and describe in detail the response to physiological and
      pathological discharge patterns. Our data suggest that the temporal propeties of
      PV+ interneuron transmission may contribute to sharp wave-ripple generation.
      These findings support the view that intrinsic and synaptic features of PV+ cells
      make them ideally suited for the generation of physiological network
      oscillations, whereas CCK+ cells implement a more subtle, graded control in the
      hippocampus.

PMID- 27038233
TI  - Chronic Conditions, New Onset, and Persistent Disability in the Ibadan Study of
      Aging.
AB  - Background.: Information about the contribution of chronic conditions to
      disability in the sub-Saharan African older persons is derived from implicit
      data. We investigated the association of chronic conditions with incident and
      persistent disability among community-dwelling elderly Nigerians. Methods.: We
      followed disability-free participants in a household cluster randomized sample of
      2,149 Nigerians, aged 65 years or older, in three waves over 5 years (2003-2009).
      Disability was measured using culturally adapted tools. Dementia and depression
      were ascertained using validated interviewer-administered measures. The presence
      of pain in six sites, angina, systemic hypertension, diabetes, heart and
      respiratory disease, and vision and hearing impairment were assessed using
      standardized self-report of clinician diagnoses. Independent predictors of
      disability were investigated using separate multivariate binomial and multinomial
      regression models with Bonferroni corrections. Results.: Among 1,887 disability
      free participants, 457 (24.2%) had incident disability over 5 years; there were
      234 (12.4%), 177 (9.4%), and 106 (5.6%) new cases in each of the waves. A total
      of 181 (10.0%) persons had disability persistently. Having a pain condition
      (relative risk ratio [RRR] = 4.7, 95% confidence interval [CI] = 2.0-11.0),
      especially when nonlocalizing (RRR = 1.5, 95% CI = 1.0-2.2), was the main
      predictor of incident disability in the study. Dementia was associated with
      cumulative deaths over 5 years (RRR = 3.5, 95% CI = 2.3-5.3). There were no
      significant associations between having a chronic condition and persistent
      disability following correction for false discovery rates. Conclusion.: Using
      direct measurements, musculoskeletal pain appears to be the most disabling
      condition in this sub-Saharan African elderly cohort surviving for up to 5 years
      with chronic conditions. Dementia may be associated with early death.

PMID- 27038234
TI  - Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia
      via c-Jun N-terminal kinase and monocyte chemoattractant protein-1.
AB  - Pathological chronic pain, which is frequently associated with prolonged tissue
      damage, inflammation, tumour invasion, and neurodegenerative diseases, gives rise
      to hyperalgesia and allodynia. We previously reported that intrathecal
      administration of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the
      orphan opioid receptor-like receptor, in the femtomole range induces touch-evoked
      allodynia. N/OFQ has been implicated in multiple signalling pathways, such as
      inhibition of cAMP production and Ca(2+) channels, or activation of K(+) channels
      and mitogen-activated protein kinase, although the signalling pathways of N/OFQ
      induced allodynia remain unclear. To address these issues, we developed an ex
      vivo mitogen-activated protein kinase assay by using intact slices of mouse
      spinal cord. N/OFQ markedly increased the phosphorylation of c-Jun N-terminal
      kinase (JNK) in the superficial dorsal horn of the spinal cord. The N/OFQ
      stimulated JNK phosphorylation was significantly inhibited by pertussis toxin,
      the phospholipase C inhibitor U73122, and the inositol trisphosphate receptor
      antagonist Xestospongin C. Intrathecal administration of the JNK inhibitor
      SP600125 inhibited N/OFQ-evoked allodynia. The N/OFQ-induced increase in JNK
      phosphorylation was observed in astrocytes that expressed glial fibrillary acidic
      protein. N/OFQ also induced monocyte chemoattractant protein-1 (MCP-1) release
      via the JNK pathway, and N/OFQ-induced JNK phosphorylation was observed in MCP-1
      immunoreactive astrocytes. Intrathecal administration of the MCP-1 receptor
      antagonist RS504393 inhibited N/OFQ-evoked allodynia. These results suggest that,
      in the spinal dorsal horn, N/OFQ induces allodynia through activation of JNK via
      the phospholipase C-inositol trisphosphate pathway, which is coupled to pertussis
      toxin-sensitive G-protein, and following the release of MCP-1 from astrocytes.

PMID- 27038235
TI  - Photocatalytic Treatment of Desalination Concentrate Using Optical Fibers Coated
      With Nanostructured Thin Films: Impact of Water Chemistry and Seasonal Climate
      Variations.
AB  - Treatment of desalination concentrate can reduce concentrate volume for disposal,
      increase water recovery and convert waste to resource. However, concentrate
      treatment is costly and energy intensive due to high concentrations of salt and
      recalcitrant organic matter in concentrate. Photocatalytic oxidation provides a
      novel energy neutral technology for concentrate treatment by degrading organic
      contaminants. Polymer-assisted hydrothermal deposition method was used to
      synthesize innovative pure and Fe-doped TiO2 mixed-phase nanocomposite thin films
      on side-glowing optical fibers (SOFs). The properties of the photocatalysts
      coated SOF were characterized by surface morphology, nanostructure, crystallite
      size and phase and zeta potential. Photodegradation efficiency and durability of
      the photocatalysts treating different types of desalination concentrate was
      studied under natural sunlight. Synthetic solutions and reverse osmosis (RO)
      concentrates from brackish water and municipal wastewater desalination facilities
      were tested to elucidate the impact of water chemistry, operating conditions and
      seasonal climate variations (solar irradiation intensity and temperature) on
      photocatalytic efficiency. High ionic strength and divalent electrolyte ions in
      RO concentrate accelerated photocatalytic process, whereas the presence of
      carbonate species and organic matter hindered photodegradation. Outdoor testing
      of immobilized continuous-flow photoreactors suggested that the catalyst-coated
      SOFs can utilize a wide spectrum of natural sunlight and achieved durable
      photocatalytic performance.

PMID- 27038236
TI  - Physiological factors influencing median nerve mobility in normal subjects.
AB  - INTRODUCTION: The purpose of this study was to assess the mobility of the median
      nerve in the axial plane in normal healthy subjects and to evaluate physiological
      factors associated with lesser degrees of mobility. METHODS: Our study included
      80 healthy volunteers between 20 and 60 years of age. For all subjects, mobility
      of the median nerve was assessed with ultrasound at the carpal tunnel. RESULTS:
      With wrist and finger flexion, the median nerve moved in all 160 wrists; in 78,
      the nerve dove deep to the flexor tendons (full), and in 82 it made a partial
      turn, but did drop below the tendons (partial). Among all demographic factors and
      sonographic measurements, only height was significantly related to partial
      mobility. CONCLUSIONS: Full or partial mobility of the median nerve with wrist
      flexion is an attribute of normal subjects; partial mobility is common,
      particularly in taller individuals. Muscle Nerve 54: 883-886, 2016.

PMID- 27038237
TI  - Adaptive responses of outer membrane porin balance of Yersinia ruckeri under
      different incubation temperature, osmolarity, and oxygen availability.
AB  - The capability of Yersinia ruckeri to survive in the aquatic systems reflects its
      adaptation (most importantly through the alteration of membrane permeability) to
      the unfavorable environments. The nonspecific porins are a key factor
      contributing to the permeability. Here we studied the influence of the stimuli,
      such as temperature, osmolarity, and oxygen availability on regulation of Y.
      ruckeri porins. Using qRT-PCR and SDS-PAGE methods we found that major porins are
      tightly controlled by temperature. Hyperosmosis did not repress OmpF production.
      The limitation of oxygen availability led to decreased expression of both major
      porins and increased transcription of the minor porin OmpY. Regulation of the
      porin balance in Y. ruckeri, in spite of some similarities, diverges from that
      system in Escherichia coli. The changes in porin regulation can be adapted in Y.
      ruckeri in a species-specific manner determined by its aquatic habitats.

PMID- 27038238
TI  - Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.
AB  - OBJECTIVE: Many JC virus antibody-positive relapsing-remitting multiple sclerosis
      (RRMS) patients who are stable on natalizumab switch to other therapies to avoid
      progressive multifocal leukoencephalopathy. METHODS: We compared outcomes for all
      RRMS patients switching from natalizumab due to JC virus antibody positivity at 3
      Swedish multiple sclerosis centers with different preferential use of rituximab
      and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64,
      fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding a total cohort of N = 256
      (fingolimod 55%). RESULTS: Within 1.5 years of cessation of natalizumab, 1.8%
      (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse
      (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43).
      The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and
      treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07
      (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were
      found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging
      examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when
      adjusting for possible confounders (age, sex, disability status, time on
      natalizumab, washout time, follow-up time, and study center). INTERPRETATION: Our
      findings suggest an improved effectiveness and tolerability of rituximab compared
      with fingolimod in stable RRMS patients who switch from natalizumab due to JC
      virus antibody positivity. Although residual confounding factors cannot be ruled
      out, the shared reason for switching from natalizumab and the preferential use of
      either rituximab or fingolimod in 2 of the centers mitigates these concerns. Ann
      Neurol 2016;79:950-958.

PMID- 27038239
TI  - Purinergic and Store-Operated Ca(2+) Signaling Mechanisms in Mesenchymal Stem
      Cells and Their Roles in ATP-Induced Stimulation of Cell Migration.
AB  - ATP is an extrinsic signal that can induce an increase in the cytosolic Ca(2+)
      level ([Ca(2+) ]c ) in mesenchymal stem cells (MSCs). However, the cognate
      intrinsic mechanisms underlying ATP-induced Ca(2+) signaling in MSCs is still
      contentious, and their importance in MSC migration remains unknown. In this
      study, we investigated the molecular mechanisms underlying ATP-induced Ca(2+)
      signaling and their roles in the regulation of cell migration in human dental
      pulp MSCs (hDP-MSCs). RT-PCR analysis of mRNA transcripts and interrogation of
      agonist-induced increases in the [Ca(2+) ]c support that P2X7, P2Y1 , and P2Y11
      receptors participate in ATP-induced Ca(2+) signaling. In addition, following P2Y
      receptor activation, Ca(2+) release-activated Ca(2+) Orai1/Stim1 channel as a
      downstream mechanism also plays a significant role in ATP-induced Ca(2+)
      signaling. ATP concentration-dependently stimulates hDP-MSC migration.
      Pharmacological and genetic interventions of the expression or function of the
      P2X7, P2Y1 and P2Y11 receptors, and Orai1/Stim1 channel support critical
      involvement of these Ca(2+) signaling mechanisms in ATP-induced stimulation of
      hDP-MSC migration. Taken together, this study provide evidence to show that
      purinergic P2X7, P2Y1 , and P2Y11 receptors and store-operated Orai1/Stim1
      channel represent important molecular mechanisms responsible for ATP-induced
      Ca(2+) signaling in hDP-MSCs and activation of these mechanisms stimulates hDP
      MSC migration. Such information is useful in building a mechanistic understanding
      of MSC homing in tissue homeostasis and developing more efficient MSC-based
      therapeutic applications. Stem Cells 2016;34:2102-2114.

PMID- 27038240
TI  - The effect and expense of redemption reintegration services versus usual
      reintegration care for young African Canadians discharged from incarceration.
AB  - African Canadians comprise 2.5% of the population, but represent 9.5% of federal
      inmates - an increase of 80% since 2003-2004. Recidivism among federal inmates is
      high (about 40%). This paper outlines the findings, at 9 months after enrolment
      during 2011-2012, of a randomised controlled trial testing the effectiveness and
      cost of Redemption Reintegration Services (RRS), a culturally specific, multi
      level intervention for young African Canadian former inmates. Retention at 9
      months was 95% of those randomised (n = 115 per group) to RRS (n = 114) or usual
      reintegration services (n = 105) offered by the municipality. The primary
      outcomes were recidivism and service costs. Mediating and moderating measures
      were Personality Strengths, Developmental Assets, Meaning in Life, the Structured
      Assessment of Violence Risk in Youth, the Youth Behaviour Checklist and
      Neighbourhood Vitality. Compared with the usual care group, the RRS group showed
      significant improvements in: self-reported Personality Strengths, Developmental
      Assets, the presence and search for Meaning in Life, social and individual risk
      factors, behaviour, and life events such as obtaining stable housing and
      enrolling in school. At 9 months, RRS participants generated significantly lower
      per person per annum expenditures for law enforcement services, housing services
      and total direct costs. Among RRS participants, 3.5% reported being re-charged
      for offences in the previous 9 months compared with 45.7% of the usual care
      group. The 2010-2011 average annual cost per person for incarceration was
      $114,364. The 48 individuals in the usual care group and 4 in RRS would generate
      costs of $5,489,472 and $457,456, respectively - a $5 million difference. We
      conclude that, at 9 months, RRS is more effective and less expensive than usual
      reintegration services for young African Canadians.

PMID- 27038241
TI  - Global epidemiology of nonalcoholic fatty liver disease: Meta-analytic assessment
      of prevalence, incidence, and outcomes.

PMID- 27038242
TI  - Pituitary apoplexy - bespoke patient management allows good clinical outcome.
AB  - OBJECTIVE: To describe the clinical presentation, management and outcome of
      pituitary apoplexy from a single centre and retrospectively apply the Pituitary
      Apoplexy Score (PAS). DESIGN: Retrospective review of patients presenting with
      classical pituitary apoplexy to a single neurosurgical centre in the Greater
      Manchester region. RESULTS: A total of 31 cases with classical pituitary apoplexy
      were identified between 2005 and 2014. The mean age at presentation was 55 years,
      and there were 19 men. In only one patient was there prior knowledge of a
      pituitary adenoma. Eleven (35%) patients were managed conservatively and 20 (65%)
      patients managed surgically. Emergency surgery was carried out in 11 patients. At
      presentation, visual symptoms were present in a higher proportion of patients in
      the surgical group (90%) compared to the conservatively managed group (64%). At
      final follow-up, visual recovery was apparent in most patients in both the
      surgical (100%) and conservatively (86%) managed groups. The proportion of
      patients with hypopituitarism was high in both the surgical (86%) and
      conservative (73%) groups at presentation, and this failed to improve at final
      follow-up (90% vs 73%, respectively). The median PAS scores were higher in the
      surgical (PAS 2), compared to the conservatively managed group (PAS 0).
      CONCLUSION: In pituitary apoplexy patients managed conservatively or surgically,
      there is good recovery of visual symptoms but not endocrine function. Patients
      should be managed on a case-by-case basis based on the severity of symptoms at
      presentation, progression of disease and surgical expertise available. Further
      prospective studies using the PAS are required to determine its usefulness in
      clinical practice.

PMID- 27038243
TI  - Definition, aims, and implementation of GA(2) LEN Urticaria Centers of Reference
      and Excellence.
AB  - BACKGROUND: GA2LEN, the Global Allergy and Asthma European Network, has recently
      launched a program for the development, interaction, and accreditation of centers
      of reference and excellence in special areas of allergy embedded in its overall
      quality management of allergy centers of excellence. The first area chosen is
      urticaria. Urticaria is a common and debilitating condition and can be a
      challenge for both patients and treating physicians, especially when chronic.
      Centers of reference and excellence in urticaria (UCAREs) can help to improve the
      management of hard-to-treat conditions such as urticaria. AIMS: Here, we describe
      the aims, the requirements and deliverables, the application process, and the
      audit and accreditation protocol for GA2LEN UCAREs. RESULTS: The main aims of
      GA2LEN UCAREs are to provide excellence in urticaria management, to increase the
      knowledge of urticaria by research and education, and to promote the awareness of
      urticaria by advocacy activities. To become a certified GA2LEN UCARE, urticaria
      centers have to apply and fulfill 32 requirements, defined by specific
      deliverables that are assessed during an audit visit. DISCUSSION AND CONCLUSION:
      The GA2LEN UCARE program will result in a strong network of urticaria
      specialists, promote urticaria research, and harmonize and improve urticaria
      management globally.

PMID- 27038244
TI  - Do founder mutations characteristic of some cancer sites also predispose to
      pancreatic cancer?
AB  - Understanding of the etiology and risk of pancreatic cancer (PaCa) is still
      poorly understood. This study evaluated the prevalence of 10 Polish founder
      mutations in four genes among PaCa patients and assessed their possible
      association with the risk of disease in Poland. In the study 383 PaCa patients
      and 4,000 control subjects were genotyped for founder mutations in: BRCA1
      (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1
      (657del5) and PALB2 (509_510delGA, 172_175delTTGT). A statistically significant
      association between the 657del5 mutation and an increased risk of pancreatic
      cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA)
      was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000
      (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509_510delGA and 172_175delTTGT
      mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8
      (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations
      combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000
      (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with
      the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1
      (657del5) was associated with an increased risk of PaCa in heterozygous carriers,
      indicating that this mutation appears to predispose to cancer of the pancreas. By
      identifying pancreatic cancer risk groups, founder mutation testing in Poland
      should be considered for people at risk for PaCa.

PMID- 27038245
TI  - What Confucius practiced is good for your mind: Examining the effect of a
      contemplative practice in Confucian tradition on executive functions.
AB  - The short-term training effects on various executive functions (EFs) by a
      movement-based contemplative practice (MBCP) are examined. Three aspects of EFs
      (working memory capacity, inhibition, switching) are assessed before and after a
      month-long 12-h training period using Body-Mind Axial Awareness (BMAA) principles
      that Confucius followers have practiced for more than 2000years. A mindfulness
      based practice (Chan-meditation) and a waiting-list control group served as
      contrast groups. Our results showed that the BMAA group performed better on the
      task that measured working memory capacity than did the Chan-meditation and the
      waiting-list groups after training. In addition, the Chan-meditation groups
      outperformed the control group on attentional switching, a novel finding for this
      kind of practice. Our findings not only show a new effect of short-term MBCPs on
      EFs, but also indicate movement-based and mindfulness-based contemplative
      practices might benefit development of various aspects of EFs in different ways.

PMID- 27038246
TI  - Preliminary investigation of multiparametric strain Z-score (MPZS) computation
      using displacement encoding with simulated echoes (DENSE) and radial point
      interpretation method (RPIM).
AB  - PURPOSE: To describe and assess an automated normalization method for identifying
      sentinel (septal) regions of myocardial dysfunction in nonischemic, nonvalvular
      dilated cardiomyopathy (DCM), using an unprecedented combination of the navigator
      gated 3D spiral displacement encoding with stimulated echoes (DENSE) magnetic
      resonance imaging (MRI), radial point interpolation (RPIM) and multiparametric
      strain z-score (MPZS). MATERIALS AND METHODS: Navigator-gated 3D spiral DENSE, in
      a 1.5T MRI machine, was used for acquiring the displacement encoded complex
      images, MR Analytical Software System (MASS) for automated boundary detection and
      automated meshfree RPIM for left-ventricular (LV) myocardial strain computation
      to analyze MPZS in 36 subjects (with n = 17 DCM patients). Pearson's r
      correlation established relations between global/sentinel MPZS and ejection
      fraction (EF). The time taken for combined RPIM-MPZS computations was recorded.
      RESULTS: Maximum MPZS differences were seen between anteroseptal and
      posterolateral regions in the base (2.0 +/- 0.3 vs. 0.9 +/- 0.5) and the mid-wall
      (2.1 +/- 0.4 vs. 1.0 +/- 0.4). These regional differences were found to be
      consistent with historically documented septal injury in nonischemic DCM.
      Correlations were 0.6 between global MPZS and EF, and 0.7 between sentinel MPZS
      and EF. The time taken for combined RPIM-MPZS computations per subject was 18.9
      +/- 5.9 seconds. CONCLUSION: Heterogeneous contractility found in the sentinel
      regions with the current automated MPZS computation scheme and the correlation
      found between MPZS and EF may lead to the creation of a new clinical metric in LV
      DCM surveillance. J. MAGN. RESON. IMAGING 2016;44:993-1002.

PMID- 27038247
TI  - Vedolizumab induction therapy for inflammatory bowel disease in clinical practice
      -a nationwide consecutive German cohort study.
AB  - BACKGROUND: Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting
      alpha4 beta7 integrin. AIM: To investigate the real-world efficacy of vedolizumab
      for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A
      consecutive cohort of 212 adult IBD patients with active disease (HBI >7/partial
      Mayo >4) newly receiving VDZ was prospectively recruited from 7 academic and 17
      community centres. The primary endpoint was clinical remission (CRM) (CD HBI <=4,
      UC pMayo <=1) in week 14. Secondary endpoints included steroid-free remission
      (SFCRM), clinical response (CRS) (HBI/pMayo score drop >=3), vedolizumab impact
      on CRP, calprotectin and haemoglobin. RESULTS: Data of 97 CD (71.1% female, HBI
      11) and 115 UC (42.6% female, pMayo 6) patients were analysed. Only 5.2% CD and
      24.3% UC were anti-TNFalpha naive. Most had extensive mucosal involvement
      (Montreal L3 69.1%/E3 53.9%). At week 14, 23.7% vs. 23.5% of CD vs. UC patients
      achieved CRM, 19.6% vs. 19.1% SFCRM and 60.8% vs. 57.4% CRS, respectively (all
      based on NRI). Week 14 CRM in CD was significantly associated with no history of
      extraintestinal manifestations (P = 0.019), no prior adalimumab use (P = 0.011),
      no hospitalisation in the past 12 months (P = 0.015) and low HBI score (P = 0.02)
      and in UC with active or previous smoking (P = 0.044/0.028) and no anti-TNFalpha
      (P = 0.023) use. Low HBI (P = 0.019) and no hospitalisation in the past 12 months
      (P = 0.01) predict CD CRM. The three most common AE were joint pain, acne and
      nasopharyngitis. CONCLUSION: Vedolizumab is effective in routine use.

PMID- 27038248
TI  - First molecular evidence for the presence of Anaplasma DNA in milk from sheep and
      goats in China.
AB  - Anaplasmosis, a disease caused by bacteria in the genus of Anaplasma, imposes
      economic constraints on animal breeders and also threatens human health. In the
      present study, we investigated the presence of Anaplasma spp. DNA in milk
      collected from sheep and goats in China. A total of 120 milk samples and 414
      field-sampled blood specimens from sheep and goats were analyzed by PCR and DNA
      sequencing. Anaplasma ovis was detected in 12 milk samples (three from sheep and
      nine from goats). The blood specimens corresponding to the A. ovis DNA-positive
      milk were analyzed for Anaplasma DNA presence, and A. ovis DNA was identified in
      10 out of the 12 blood specimens. One goat's milk sample was Anaplasma bovis DNA
      positive, as was the corresponding blood sample. Anaplasma phagocytophilum was
      found in a milk sample and blood sample from one goat. One milk sample from Xinmi
      in Henan province was simultaneously positive for A. bovis and A.
      phagocytophilum; however, the corresponding blood was negative for both species.
      DNA sequencing of the PCR products and phylogenetic analysis confirmed that the
      sequences from the milk samples matched those of the corresponding blood samples.
      This is the first report to detect the Anaplasma DNA in milk samples under
      natural condition, and represents the first evidence of the presence of A. ovis,
      A. bovis and A. phagocytophilum DNA in milk from sheep and goats. 

PMID- 27038249
TI  - Pediculosis capitis is a growing neglected infestation due to migration in
      southeast Turkey.
AB  - Demographic, socio-economical, and environmental changes affecting prevalence of
      Pediculosis capitis. The aim of this study was to investigate the prevalence of
      P. capitis and external factors affecting the distribution of P. capitis. A total
      of 6004 primary-school students between 5 and 11 years were screened for P.
      capitis at 28 different primary-schools in Gaziantep, located in southeastern of
      Turkey, during different two education terms (First education term is in
      September 2013 to May 2014, second education term is in September 2014 and May
      2015). The prevalence of P. capitis was found to be positive 1.5 % (90/6004) and
      6.9 % (415/6004) in first education term and in second education term,
      respectively. In this study shown that the rate of P. capitis's prevalence was
      increased 5.4 % in Gaziantep. P. capitis is a neglected infestation and it has re
      emerged in Gaziantep, located in the southeastern of Turkey. Health staff member
      must improve health education programs in primary-school students especially girl
      students. 

PMID- 27038250
TI  - Survivability of Kudoa septempunctata in human intestinal conditions.
AB  - To elucidate whether Kudoa septempunctata was able to live in the human
      intestine, we assessed viability of K. septempunctata sporoplasms under
      conditions that mimicked human and ragworm digestive tracts. To study the effect
      of osmotic pressure on viability, sporoplasms were incubated in 0.9 or 3.4 %
      sodium chloride solutions, which roughly corresponded to the osmotic pressure in
      human or ragworm tissues, respectively. While viability in 3.4 % sodium chloride
      did not change after 72 h, it dropped to 21 % in 0.9 % sodium chloride. To study
      the effect of temperature on viability, sporoplasms were incubated at 37, 15, or
      25  degrees C, which were representative of human, winter ragworm, or summer
      ragworm temperatures, respectively. Viability decreased sharply to 8.4 % after 48
      h at 37  degrees C, but remained essentially unchanged at 15 and 25  degrees C.
      In addition, sporoplasms showed strong susceptibility to bile. These results
      indicate that K. septempunctata could not live in the human intestine for a long
      time. 

PMID- 27038251
TI  - The hair grooming practices of women of African descent in London, United
      Kingdom: findings of a cross-sectional study.
AB  - BACKGROUND: There is a lack of published data pertaining to the hair grooming
      practices of women of African descent in Europe. However, these data are
      important in facilitating culturally appropriate discussions on hair loss
      prevention. OBJECTIVE: We sought to describe the hair grooming practices of adult
      women of African descent in London, UK. METHOD: Analysis of pooled data collected
      from a questionnaire-based study exploring correlates of hair loss in women of
      African descent in London. RESULTS: A maximum of 242 subjects were included in
      the final data analysis. Subjects had a mean age of 41.1 years (CI: 39.3-42.9)
      and exhibited a diverse range of scalp hair phenotypes, although the majority
      (76.3%) had type 6, 7 or 8 hair. A percentage of 64.9 had more than five
      different hairstyles since childhood, with natural hairstyles being the most
      frequent current hairstyle (52.6%). The mean frequency of hair washing was 17.9
      days (CI: 15.8-20.0), increasing to 32.8 days (28.6-37.0) when hair was braided
      or in a weave. The mean frequency of hair braiding/weaving was 63 days (CI: 56.3
      69.7), whereas that for application of chemical relaxers was 88.6 days (CI: 75.6
      101.6). While 59.2% of subjects avoided concurrent use of hair colours and
      chemical relaxers, only 46.3% avoided braiding chemically relaxed hair.
      CONCLUSIONS: The hair-care practices of women of African descent should be borne
      in mind when treating hair and scalp disorders in this group. Although the
      current trend is towards natural hairstyles, some adverse hair-care practices
      still persist which should be addressed through culturally appropriate public
      health messages on hair loss prevention.

PMID- 27038252
TI  - Controlled Variable Oxidative Doping of Individual Organometallic Nanoparticles.
AB  - The charging and controlled oxidative doping of single organometallic ferrocene
      nanoparticles is reported in aqueous sodium tetrafluoroborate using the nano
      impacts method. It is shown that ferrocene nanoparticles of approximately 105 nm
      diameter are essentially quantitatively oxidatively doped with the uptake of one
      tetrafluoroborate anion per ferrocene molecule at suitably high overpotentials.
      By using lower potentials, it is possible to achieve low doping levels of single
      nanoparticles in a controlled manner.

PMID- 27038253
TI  - Molecular Dynamics Simulations of Ligand-Induced Flap Conformational Changes in
      Cathepsin-D-A Comparative Study.
AB  - The flap region in aspartic proteases is a unique structural feature to this
      class of enzymes, and found to have a profound impact on protein overall
      structure, function, and dynamics. Understanding the structure and dynamic
      behavior of the flap regions is crucial in the design of selective inhibitors
      against aspartic proteases. Cathepsin-D, an aspartic protease enzyme, has been
      implicated in a long list of degenerative diseases as well as breast cancer
      progression. Presented herein, for the first time, is a comprehensive description
      of the conformational flap dynamics of cathepsin-D using a comparative 50 ns
      "multiple" molecular dynamics simulations. Diverse collective metrics were
      proposed to accurately define flap dynamics. These are distance d1 between the
      flap tips residues (Gly79 and Met301); dihedral angle phi; in addition to
      TriCalpha angles Gly79-Asp33-Asp223, theta1 , and Gly79-Asp223-Met301, theta2 .
      The maximum distance attained throughout the simulation was 17.42 and 11.47 A for
      apo and bound cathepsin-D, respectively, while the minimum distance observed was
      8.75 and 6.32 A for apo and bound cathepsin-D, respectively. The movement of the
      flap as well as the twist of the active pocket can properly be explained by
      measuring the angle, theta1 , between Gly79-Asp33-Met301 and correlating it with
      the distance Calpha of the flap tip residues. The asymmetrical opening of the
      binding cavity was best described by the large shift of -6.26 degrees  to +20.94
      degrees  in the dihedral angle, phi, corresponding to the full opening of the
      flap at a range of 31-33 ns. A wide-range of post-dynamic analyses was also
      applied in this report to supplement our findings. We believe that this report
      would augment current efforts in designing potent structure-based inhibitors
      against cathepsin-D in the treatment of breast cancer and other degenerative
      diseases. J. Cell. Biochem. 117: 2643-2657, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27038254
TI  - Bisphenol A Increases the Migration and Invasion of Triple-Negative Breast Cancer
      Cells via Oestrogen-related Receptor Gamma.
AB  - Triple-negative breast cancer (TNBC) is characterized by great metastasis and
      invasion capability. Our study revealed that nanomolar bisphenol A (BPA), one of
      the most ubiquitous endocrine disruptors, can increase wound closure and invasion
      of both MDA-MB-231 and BT-549 cells. BPA treatment can increase protein and mRNA
      expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while had no effect
      on the expression of vimentin (Vim) and fibronectin (FN) in TNBC cells. The
      expression of G-protein-coupled receptor (GPER), which has been suggested to
      mediate rapid oestrogenic signals, was not varied in BPA-treated MDA-MB-231 and
      BT-549 cells. Its inhibitor G15 also had no effect on BPA-induced MMPs expression
      and cell invasion. Interestingly, BPA treatment can significantly increase the
      mRNA and protein expressions of oestrogen-related receptor gamma (ERRgamma), but
      not ERRalpha or ERRbeta, in both MDA-MB-231 and BT-549 cells. The knock-down of
      ERRgamma can markedly attenuate BPA-induced expression of MMP-2 and MMP-9 in TNBC
      cells. BPA treatment can activate both ERK1/2 and Akt in TNBC cells. Both
      inhibitors of ERK1/2 (PD98059) and Akt (LY294002) can attenuate BPA-induced
      ERRgamma expression and cell invasion of MDA-MB-231 cells. Collectively, our data
      revealed that BPA can increase the expression of MMPs and in vitro motility of
      TNBC cells via ERRgamma. Both activation of ERK1/2 and Akt participated in this
      process. Our study suggests that more attention should be paid to the roles of
      xenoestrogens such as BPA in the development and progression of TNBC. 

PMID- 27038255
TI  - pi-Extended "Earring" Porphyrins with Multiple Cavities and Near-Infrared
      Absorption.
AB  - beta,beta-tripyrrin-bridged earring porphyrins were synthesized through Suzuki
      Miyaura cross coupling reactions. These porphyrinoids have multiple cavities and
      can accommodate two or three metal ions per molecule. The structures of the
      porphyrins have been elucidated by x-ray diffraction analysis, and feature curved
      pi planes. The electronic spectra of the porphyrins exhibit near-infrared (NIR)
      absorptions and metal insertion leads to red-shifted and intensified absorption
      features. Electrochemical analysis and transient absorption measurements
      indicated that the porphyrins exhibit effective electronic communication between
      their central and peripheral moieties.

PMID- 27038257
TI  - Reaction monitoring using NMR.

PMID- 27038256
TI  - Double-Sided Junctions Enable High-Performance Colloidal-Quantum-Dot
      Photovoltaics.
AB  - The latest advances in colloidal-quantum-dot material processing are combined
      with a double-sided junction architecture, which is done by efficiently
      incorporating indium ions in the ZnO eletrode. This platform allows the
      collection of all photogenerated carriers even at the maximum power point. The
      increased depletion width in the device facilitates full carrier collection,
      leading to a record 10.8% power conversion efficiency. 

PMID- 27038258
TI  - Dihydroartemisinin alleviates bile duct ligation-induced liver fibrosis and
      hepatic stellate cell activation by interfering with the PDGF-betaR/ERK signaling
      pathway.
AB  - Liver fibrosis represents a frequent event following chronic insult to trigger
      wound healing responses in the liver. Activation of hepatic stellate cells
      (HSCs), which is a pivotal event during liver fibrogenesis, is accompanied by
      enhanced expressions of a series of marker proteins and pro-fibrogenic signaling
      molecules. Artemisinin, a powerful antimalarial medicine, is extracted from the
      Chinese herb Artemisia annua L., and can inhibit the proliferation of cancer
      cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is
      able to attenuate lung injury and fibrosis. However, the effect of DHA on liver
      fibrosis remains unclear. The aim of this study was to investigate the effect of
      DHA on bile duct ligation-induced injury and fibrosis in rats. DHA improved the
      liver histological architecture and attenuated collagen deposition in the
      fibrotic rat liver. Experiments in vitro showed that DHA inhibited the
      proliferation of HSCs and arrested the cell cycle at the S checkpoint by altering
      several cell-cycle regulatory proteins. Moreover, DHA reduced the protein
      expressions of a-SMA, alpha1 (I) collagen and fibronectin, being associated with
      interference of the platelet-derived growth factor beta receptor (PDGF-betaR)
      mediated ERK pathway. These data collectively revealed that DHA relieved liver
      fibrosis possibly by targeting HSCs via the PDGF-betaR/ERK pathway. DHA may be a
      therapeutic antifibrotic agent for the treatment of hepatic fibrosis. 

PMID- 27038259
TI  - Energy conversion of biomass crops and agroindustrial residues by combined
      biohydrogen/biomethane system and anaerobic digestion.
AB  - Aim of this study was to evaluate the suitability of ensiled giant reed, ensiled
      maize, ensiled olive pomace, wheat bran for combined systems (CS: dark
      fermentation+anaerobic digestion (AD)) producing hydrogen-rich biogas
      (biohythane), tested in batch under basic operational conditions (mesophilic
      temperatures, no pH control). Substrates were also analyzed under a single stage
      AD batch test, in order to investigate the effects of DF on estimated energy
      recovery (ER) in combined systems. In CS, maize and wheat bran exhibited the
      highest hydrogen potential (13.8 and 18.9NLkgVS(-1)) and wheat bran the highest
      methane potential (243.5NLkgVS(-1)). In one-stage AD, giant reed, maize and wheat
      bran showed the highest methane production (239.5, 267.3 and 260.0NLkgVS(-1)).
      Butyrate/acetate ratio properly described the dark fermentation, correlating with
      hydrogen production (r=0.92). Wheat bran proved to be a promising residue for CS
      in terms of hydrogen/methane potential and ER. 

PMID- 27038260
TI  - Enhanced solution velocity between dark and light areas with horizontal tubes and
      triangular prism baffles to improve microalgal growth in a flat-panel photo
      bioreactor.
AB  - Novel horizontal tubes and triangular prism (HTTP) baffles that generate flow
      vortices were developed to increase solution velocity between dark and light
      areas and thus improve microalgal growth in a flat-panel photo-bioreactor.
      Solution velocity, mass-transfer coefficient, and mixing time were measured with
      a particle-imaging velocimeter, dissolved oxygen probes, and pH probes. The
      solution mass-transfer coefficient increased by 30% and mixing time decreased by
      21% when the HTTP baffles were used. The solution velocity between dark and light
      areas increased from ~0.9cm/s to ~3.5cm/s, resulting in a decreased dark-light
      cycle period to one-fourth. This enhanced flashing light effect with the HTTP
      baffles dramatically increased microalgae biomass yield by 70% in the flat-panel
      photo-bioreactor. 

PMID- 27038261
TI  - Hydraulic retention time effects on wastewater nutrient removal and bioproduct
      production via rotating algal biofilm reactor.
AB  - Rotating algal biofilm reactor (RABR) technology was successfully employed in an
      effective strategy to couple the removal of wastewater nutrients with
      accumulation of valuable bioproducts by grown algae. A secondary stage municipal
      wastewater was fed to the developed system and the effects of the hydraulic
      retention time (HRT) parameter on both nutrient removal and bioproduct production
      were evaluated under fed-batch operation mode. Two sets of bench scale RABRs were
      designed and operated with HRTs of 2 and 6days in order to provide competitive
      environment for algal growth. The HRT significantly affected nitrogen and
      phosphorus uptakes along with lipid and starch accumulations by microalgae in
      harvested biofilms. Domination of nitrogen removal in 2-day HRT with higher lipid
      accumulation (20% on dried weight basis) and phosphorus removal in 6-day HRT with
      higher starch production (27% on dried weight basis) was observed by comparing
      the performances of the RABRs in duplicate runs. 

PMID- 27038262
TI  - Methane enhancement through co-digestion of chicken manure and thermo-oxidative
      cleaved wheat straw with waste activated sludge: A C/N optimization case.
AB  - The present study emphasized the co-digestion of the thermal-H2O2 pretreated
      wheat straw (WS) and chicken manure (CM) with the waste activated sludge at four
      levels of C/N (35:1, 30:1, 25:1 and 20:1). All C/N compositions were found
      significant (P<0.05) to enhance methane generation and process stability during
      the anaerobic co-digestion of WS and CM. The experimental results revealed that
      the composition having C/N value of 20:1 was proved as optimum treatment with the
      methane enhancing capability of 85.11%, CODs removal efficiency of 48.55% and
      66.83% VS removal as compared with the untreated WS. The other compositions
      having C/N of 25:1, 30:1 and 35:1 provided 75.85%, 63.04% and 59.96% enhanced
      methane respectively as compared with the control. Pretreatment of the WS reduced
      its C/N value up to 65%. Moreover, to optimize the most suitable C/N composition,
      the process stability of the co-digestion of WS and CM was deeply monitored. 

PMID- 27038263
TI  - Trace heavy metal ions promoted extracellular electron transfer and power
      generation by Shewanella in microbial fuel cells.
AB  - Although microbial fuel cells (MFCs) is considered as one of the most promising
      technology for renewable energy harvesting, low power output still accounts one
      of the bottlenecks and limits its further development. In this work, it is found
      that Cu(2+) (0.1MUgL(-1)-0.1mgL(-1)) or Cd(2+) (0.1MUgL(-1)-1mgL(-1))
      significantly improve the electricity generation in MFCs. The maximum power
      output achieved with trace level of Cu(2+) (~6nM) or Cd(2+) (~5nM) is 1.3 times
      and 1.6 times higher than that of the control, respectively. Further analysis
      verifies that addition of Cu(2+) or Cd(2+) effectively improves riboflavin
      production and bacteria attachment on the electrode, which enhances bacterial
      extracellular electron transfer (EET) in MFCs. These results unveil the mechanism
      for power output enhancement by Cu(2+) or Cd(2+) addition, and suggest that metal
      ion addition should be a promising strategy to enhance EET as well as power
      generation of MFCs. 

PMID- 27038264
TI  - Bioconversion of volatile fatty acids derived from waste activated sludge into
      lipids by Cryptococcus curvatus.
AB  - Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS)
      was used to produce microbial lipids as culture medium in this study, which aimed
      to realize the resource recovery of WAS and provide low-cost feedstock for
      biodiesel production simultaneously. Cryptococcus curvatus was selected among
      three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch
      cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen
      ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by
      struvite precipitation. The lipid content further increased to 39.6% and the
      biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using
      sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA
      solution contained nearly 50% of monounsaturated fatty acids, including palmitic
      acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic
      acid, which showed the adequacy of biodiesel production. 

PMID- 27038265
TI  - Preparation of ferric-activated sludge-based adsorbent from biological sludge for
      tetracycline removal.
AB  - Ferric activation was novelly used to produce sludge-based adsorbent (SBA) from
      biological sludge through pyrolysis, and the adsorbents were applied to remove
      tetracycline from aqueous solution. The pyrolysis temperature and mass ratio
      (activator/dried sludge) greatly influenced the surface area and pore
      characteristics of SBA. Ferric activation could promote the porous structure
      development of adsorbents, and the optimum preparation conditions were pyrolysis
      temperature 750 degrees C and mass ratio (activator/dried sludge) 0.5. In batch
      experiments, ferric-activated SBA showed a higher adsorption capacity for
      tetracycline than non-activated SBA, because the enhanced mesoporous structure
      favored the diffusion of tetracycline into the pores, the iron oxides and oxygen
      containing functional groups in the adsorbents captured tetracycline by surface
      complexation. The results indicate that ferric activation is an effective
      approach for preparing adsorbents from biological sludge to remove tetracycline,
      providing a potential option for waste resource recovery. 

PMID- 27038266
TI  - Essential factors of an integrated moving bed biofilm reactor-membrane
      bioreactor: Adhesion characteristics and microbial community of the biofilm.
AB  - This work aims at revealing the adhesion characteristics and microbial community
      of the biofilm in an integrated moving bed biofilm reactor-membrane bioreactor,
      and further evaluating their variations over time. With multiple methods, the
      adhesion characteristics and microbial community of the biofilm on the carriers
      were comprehensively illuminated, which showed their dynamic variation along with
      the operational time. Results indicated that: (1) the roughness of biofilm on the
      carriers increased very quickly to a maximum value at the start-up stage, then,
      decreased to become a flat curve, which indicated a layer of smooth biofilm
      formed on the surface; (2) the tightly-bound protein and polysaccharide was the
      most important factor influencing the stability of biofilm; (3) the development
      of biofilm could be divided into three stages, and Gammaproteobacteria were the
      most dominant microbial species in class level at the last stage, which occupied
      the largest ratio (51.48%) among all microbes. 

PMID- 27038267
TI  - Identification and functional characterization of four transient receptor
      potential ankyrin 1 variants in Apolygus lucorum (Meyer-Dur).
AB  - As signal integrators that respond to various physical and chemical stimuli,
      transient receptor potential (TRP) channels fulfil critical functional roles in
      the sensory systems of both vertebrate and invertebrate organisms. Here, four
      variants of TRP ankyrin 1 (TRPA1) were identified and cloned from the green plant
      bug, Apolygus lucorum. Spatiotemporal expression profiling across development and
      in different adult tissues revealed that the highest relative-transcript levels
      occurred in first-instar nymphs and antennae, respectively. In Xenopus laevis
      based functional assays, Apo. lucorum TRPA1-A (AlucTRPA1-A), AlucTRPA1-B and
      AlucTRPA1-C were activated by increasing the temperature from 20 to 40  degrees C
      with no significant desensitization observed after repeated temperature stimuli.
      The activation temperature of AlucTRPA1-A and AlucTRPA1-B was < 25  degrees C,
      whereas the activation temperature of AlucTRPA1-C was between 25 and 30  degrees
      C. Amongst the variants, only AlucTRPA1-A and AlucTRPA1-C were directly activated
      by high concentrations of allyl isothiocyanate, cinnamaldehyde and citronellal.
      Taken together, these results suggest that AlucTRPA1 variants may function in
      vivo as both thermal and chemical sensors, with the four variants potentially
      mediating different physiological functions. This study not only enriches our
      understanding of TRPA1 function in Hemiptera (Miridae), but also offers a
      foundation for developing new pest control strategies.

PMID- 27038268
TI  - In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1
      and 17A2 Proteins from Zebrafish.
AB  - Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17alpha
      hydroxylation and 17alpha,20-lyase reactions. Fish P450 17A2 catalyzes only
      17alpha-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane
      proteins that bind to the membrane through their N-terminal hydrophobic segment,
      the signal anchor sequence. The presence of this N-terminal region renders
      expression of full-length proteins challenging or impossible. For some proteins,
      variable truncation of the signal anchor sequence precludes expression or results
      in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain
      insight into their different activities, we used an alternative N-terminal
      sequence to boost expression together with in situ proteolysis. Key features of
      our approach to identify crystallizable P450 fragments were the use of an N
      terminal leader sequence, a screen composed of 12 proteases to establish optimal
      cleavage, variations of protease concentration in combination with an SDS-PAGE
      assay, and analysis of the resulting fragments using Edman sequencing. Described
      in this unit are protocols for vector preparation, expression, purification, and
      in situ proteolytic crystallization of two membrane-bound P450 proteins.

PMID- 27038269
TI  - The Use of Detergents to Purify Membrane Proteins.
AB  - Extraction of membrane proteins from biological membranes is usually accomplished
      with the help of detergents. This unit describes the use of detergents to
      solubilize and purify membrane proteins. The chemical and physical properties of
      the different classes of detergents typically used with biological samples are
      discussed. A separate section addresses the compatibility of detergents with
      applications downstream of the membrane protein purification process, such as
      optical spectroscopy, mass spectrometry, protein crystallography, biomolecular
      NMR, or electron microscopy. A brief summary of alternative membrane protein
      solubilizing and stabilizing systems is also included. Protocols in this unit
      include the isolation and solubilization of biological membranes and phase
      separation; support protocols for detergent removal, detergent exchange, and the
      determination of critical micelle concentration using different methods are also
      included.

PMID- 27038270
TI  - Obtaining Soluble Folded Proteins from Inclusion Bodies Using Sarkosyl, Triton X
      100, and CHAPS: Application to LB and M9 Minimal Media.
AB  - This unit describes a straightforward and efficient method of using sarkosyl to
      solubilize and recover difficult recombinant proteins, such as GST- and His6 
      tagged fusion proteins, that are overexpressed in E. coli. This protocol is
      especially useful for rescuing recombinant proteins overexpressed in M9 minimal
      medium. Sarkosyl added to lysis buffers helps with both protein solubility and
      cell lysis. Higher percentage sarkosyl (up to 10%) can extract >95% of soluble
      protein from inclusion bodies. In the case of sarkosyl-solubilized GST-fusion
      proteins, batch-mode affinity purification requires addition of a specific ratio
      of Triton X-100 and CHAPS, while sarkosyl-solubilized His6 -tagged fusion
      proteins can be directly purified on Ni(2+) resin columns. Proteins purified by
      this method could be widely used in biological assays, structure analysis and
      mass spectrum assay.

PMID- 27038271
TI  - Use of Protein Folding Reagents.
AB  - The reagents and methods for purification and use of the most commonly used
      denaturants, guanidine hydrochloride (guanidine-HCl) and urea, are described.
      Other protein denaturants and reagents used to fold proteins are briefly
      mentioned. Sulfhydryl reagents (reducing agents) and "oxido-shuffling" (or
      oxidative regeneration) systems are also described.

PMID- 27038272
TI  - Protein Precipitation Using Ammonium Sulfate.
AB  - The basic theory of protein precipitation by addition of ammonium sulfate is
      presented, and the most common applications are listed. Tables are provided for
      calculating the appropriate amount of ammonium sulfate to add to a particular
      protein solution.

PMID- 27038273
TI  - First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical
      practice: Patients' outcome and analysis of prognostic factors.
AB  - FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer
      (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated
      efficacy in metastatic colorectal cancer. We aimed to evaluate activity and
      tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative
      prognostic factors. One hundred thirty-seven consecutive aPC patients were
      treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical,
      laboratory and pathological data were collected and their association with
      activity, progression free survival (PFS) and overall survival (OS) was
      investigated. After a median follow up of 30 months, median PFS and OS were 8.0
      months (95% CI 6.19-9.81) and 12 months (95% CI 9.75-14.25), respectively.
      Response rate was 38.6%, while disease-control rate 72.2%. At multivariate
      analysis liver metastases (p = 0.019; Hazard Ratio, HR, 0.59, 95% Confidence
      Interval, CI, 0.380.96), Eastern Cooperative Oncology Group (ECOG) performance
      status (PS) 1 (p = 0.001; HR 2.26, 95%CI 1.42-3.59) and neutrophil-lymphocyte
      ratio (NLR)> 4 (p= 0.002; HR: 2.42; 95% CI 1.38-4.25) were associated with poorer
      OS. We categorized 119 pts with complete available data as good-risk (0 factors,
      38 pts), intermediate-risk (1 factor, 49 pts) and poor-risk (>=2 factors, 32
      pts). Median OS for these three groups were 17.6, 11.1 and 7.4 months,
      respectively (p < 0.001). FOLFOXIRI is active and feasible in aPC. Prognosis of
      aPC pts treated with FOLFOXIRI is influenced by easily available factors: our
      analysis revealed ECOG PS, liver metastases and NLR as the most important
      predictors of survival. These factors could be helpful for treatment decision and
      clinical trial design. 

PMID- 27038274
TI  - Corrigendum to "Generalizing memories over time: Sleep and reinforcement
      facilitate transitive inference" [Neurobiol. Learn. Memory 100 (2013) 70-76].

PMID- 27038275
TI  - Parents' Perspective of Quality of Life of Retinoblastoma Survivors.
AB  - Health-related quality of life (HRQOL) in retinoblastoma survivors was assessed
      using parent proxy report of PedsQL(TM) 4.0 generic core scale. One hundred
      twenty-two parents of retinoblastoma survivors filled the questionnaire
      satisfactorily. This was compared with parent-reported HRQOL of 50 siblings. The
      median age of survivors was 98 (range, 60-247) months and male:female ratio was
      2:1. The overall parent-reported HRQOL was significantly worse in survivors as
      compared to controls (74.4 +/- 8.5 vs. 85.1 +/- 4.6, P < 0.001). All health
      domains were significantly affected when compared with controls. None of the
      baseline and treatment-related factors predicted HRQOL.

PMID- 27038276
TI  - A large family of anti-activators accompanying XylS/AraC family regulatory
      proteins.
AB  - AraC Negative Regulators (ANR) suppress virulence genes by directly down
      regulating AraC/XylS members in Gram-negative bacteria. In this study, we sought
      to investigate the distribution and molecular mechanisms of regulatory function
      for ANRs among different bacterial pathogens. We identified more than 200 ANRs
      distributed in diverse clinically important gram negative pathogens, including
      Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp.,
      enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the
      Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and
      surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR-activated
      regulator), a prototype member of the ANR family in EAEC, binds with high
      affinity to the central linker domain of AraC-like member AggR. ANR-AggR binding
      disrupted AggR dimerization and prevented AggR-DNA binding. ANR homologs of
      Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable
      of complementing Aar activity by repressing aggR expression in EAEC strain 042.
      ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other
      members of the AraC family, including Rns and ToxT. The predicted proteins of all
      ANR members exhibit three highly conserved predicted alpha-helices. Site-directed
      mutagenesis studies suggest that at least predicted alpha-helices 2 and 3 are
      required for Aar activity. In sum, our data strongly suggest that members of the
      novel ANR family act by directly binding to their cognate AraC partners.

PMID- 27038277
TI  - Laparoscopic right colectomy vs laparoscopic-assisted colonoscopic polypectomy
      for endoscopically unresectable polyps: a randomized controlled trial.
AB  - AIM: A randomized controlled trial (RCT) was conducted to test the null
      hypothesis that there is no difference in complication rates and length of stay
      (LOS) between laparoscopic right colectomy (LRC) and laparoscopic-assisted
      colonoscopic polypectomy (LACP) for endoscopically unresectable polyps of the
      right colon. METHOD: A single-centre RCT (NCT01986699) was conducted on patients
      with polyps of the right colon deemed by the gastroenterologist to be
      unresectable. Patients underwent a repeat colonoscopy with biopsy by an
      interventional endoscopist and were allocated to LRC or LACP. Patients with a
      nonlift sign, dysplasia, adenocarcinoma, inflammatory bowel disease or familial
      adenomatous polyposis were excluded from the trial. The study was powered to
      detect a 73% difference in the LOS which required 17 patients in each arm with an
      alpha error of 0.05 and a power of 95%. RESULTS: Thirty-four patients were
      comparable for age (P = 0.919), gender (P = 0.364), body mass index (P = 0.634),
      American Society of Anesthesiologists class (P = 0.388) and previous abdominal
      surgery (P = 0.366). There was no significant difference in the preoperative
      morphology (P = 0.485), location (P = 0.297), size (P = 0.690) or histology of
      the polyps (P = 0.779). LRC patients experienced a longer operating time (180 vs
      90 min; P = 0.001), required more intravenous infusion (3.1 vs 2.0 l; P = 0.025),
      took significantly longer to pass flatus (2.88 vs 1.44 days; P < 0.001), resumed
      solid food later (3.94 vs 1.69 days; P < 0.001) and had a longer postoperative
      LOS (4.94 vs 2.63 days; P < 0.001). Postoperative complications (P = 0.656),
      readmissions (P = 0.5) and reoperations (P = 0.5) did not differ. Final size (P =
      0.339) and histology (P = 0.104) of the polyps did not differ. There were four
      cancers in the LRC arm. At follow-up colonoscopy with biopsy of the scar in 10
      patients at 15.3 months, one patient had recurrence of the polyp at the site of
      the previous LACP. CONCLUSION: LACP and LRC had similar complication rates, but
      LOS was shorter after LACP.

PMID- 27038278
TI  - Intelligence quotient in paediatric sickle cell disease: a systematic review and
      meta-analysis.
AB  - AIM: Sickle cell disease (SCD) is the commonest cause of childhood stroke
      worldwide. Magnetic resonance imaging (MRI) is routinely used to detect
      additional silent cerebral infarction (SCI), as IQ is lower in SCI as well as
      stroke. This review assesses the effect of infarction on IQ, and specifically
      whether, compared to healthy controls, IQ differences are seen in children with
      SCI with no apparent MRI abnormality. METHOD: A systematic review was conducted
      to include articles with an SCD paediatric population, MRI information, and
      Wechsler IQ. A meta-analysis of 19 articles was performed to compare IQ in three
      groups: stroke vs SCI; SCI vs no SCI; and no SCI vs healthy controls. RESULTS:
      Mean differences in IQ between all three groups were significant: stroke patients
      had lower IQ than patients with SCI by 10 points (six studies); patients with SCI
      had lower IQ than no patients with SCI by 6 points (17 studies); and no patients
      with SCI had lower IQ than healthy controls by 7 points (seven studies).
      INTERPRETATION: Children with SCD and no apparent MRI abnormality have
      significantly lower IQ than healthy controls. In this chronic condition, other
      biological, socioeconomic, and environmental factors must play a significant role
      in cognition.

PMID- 27038279
TI  - A flexible nanofiber-based membrane with superhydrophobic pinning properties.
AB  - A nanofiber-based TiO2(B)/carbon nanofiber membrane has been synthesized by a
      facile and effective route that incorporates electrospinning approach with
      hydrothermal method. The prepared membrane shows high flexibility and
      hydrophilicity. After treatment with a low surface energy fluorosilane, the
      obtained superhydrophobic surface endows the membrane a high adhesive force due
      to the hybrid microstructure of TiO2(B) nanotubes and nanoplates on fibers. A
      water droplet on the surface of the membrane appears spherical in shape, which
      cannot roll off even when the membrane is bent and turned upside down. When a
      water droplet dropped from a certain height above the tilt membrane, the rolled
      water droplet can be stopped after a small displacement. In addition, a 12 MUl
      water droplet can be quickly captured from a hydrophobic surface by curvature
      change of the superhydrophobic TiO2(B)/carbon nanofiber membrane. The membrane
      with excellent static and dynamic pinning performance to water may be expected to
      apply to biomedical and microfluidic devices.

PMID- 27038280
TI  - Green synthesis of the Cu/ZnO nanoparticles mediated by Euphorbia prolifera leaf
      extract and investigation of their catalytic activity.
AB  - A green synthesis process was developed for the preparation of the Cu/ZnO
      nanoparticles (NPs) using Euphorbia prolifera leaf extract as a mild, renewable
      and non-toxic reducing agent and efficient stabilizer without using dangerous,
      hazardous and toxic materials. The approach of biosynthesis appears to be cost
      efficient eco-friendly and easy alternative to conventional methods of the Cu/ZnO
      NPs synthesis. The Cu/ZnO NPs were characterized by FESEM, EDS, elemental
      mapping, TEM and XRD. TEM micrograph has shown the formation of Cu NPs with the
      size in the range of 5-17 nm. In addition, the synthesized Cu/ZnO NPs presented
      excellent catalytic activity for the degradation of Methylene blue (MB) and Congo
      red (CR) in the presence of NaBH4 in water at room temperature.

PMID- 27038281
TI  - Incorporation of negatively charged iron oxide nanoparticles in the shell of
      anionic surfactant-stabilized microbubbles: The effect of NaCl concentration.
AB  - We report on the key effect of NaCl for the stabilization of nanoparticle
      decorated microbubbles coated by an anionic perfluoroalkylated phosphate
      C10F21(CH2)2OP(O)(OH)2 surfactant and negatively charged iron oxide
      nanoparticles. We show that hollow microspheres with shells of 100-200 nm in
      thickness can be stabilized even at high pH when a strong ionic force is required
      to screen the negative charges. Due to the more drastic conditions required to
      stabilize the hollow microspheres, they appear to be stable enough to be
      deposited on a surface and dried. That can be a simple way to fabricate porous
      ceramics.

PMID- 27038282
TI  - Nucleation, growth, and dissolution of silver nanostructures formed in
      nanotubular J-aggregates of amphiphilic cyanine dyes.
AB  - Solution fabricated high aspect ratio silver nanowires are of interest because of
      their usability in plasmonic devices or transparent electrodes. Recently, silver
      nanowires with diameters of 6.5 nm and lengths exceeding tens or hundreds of
      microns were grown by reduction of silver ions within the inner volume of
      nanotubular J-aggregates of an amphiphilic cyanine dye. Unlike in other soft
      template systems, the anisotropic growth of the silver wires is not caused by
      different screening of the diverse facets of silver crystals. Instead, the shape
      of the wires replicates the inner space of the tubes without destroying the
      template. This effect is demonstrated by ex-situ observation of the growth of the
      silver wires via transmission electron microscopy. The wire growth is initiated
      by exposure to blue light and starts with small, isolated crystallites within the
      tubular aggregates. The crystallites grow into pieces of wires that finally
      coalesce into continuous wires. The growth is mediated by material transport
      through the membrane-like wall of the dye aggregates. This wall permeability is
      further demonstrated by dissolution of the silver wires via oxidative etching by
      addition of sodium chloride. It is concluded that the cyanine double layer wall
      is permeable for ions such as silver, sodium, chlorine, and water molecules. This
      permeability permits control of the wire length through the concentration of
      chlorine when oxygen is removed from the solvent.

PMID- 27038283
TI  - Size-based separation of supercoiled plasmid DNA using ultrafiltration.
AB  - HYPOTHESIS: Most previous studies of membrane-based separations have shown no
      effect of DNA size on plasmid transmission through small pore size
      ultrafiltration membranes, consistent with the predicted behavior for flexible
      polymer chains. However, supercoiled plasmids are known to have a highly
      "branched" structure with the number of branches dependent on the DNA length.
      This difference in branching could lead to a significant dependence of the
      transmission on the plasmid size, providing opportunities for size-based
      separations using ultrafiltration. EXPERIMENTS: Data were obtained with 3.0, 9.8,
      and 16.8 kbp plasmids using both cellulosic and polyethersulfone ultrafiltration
      membranes with different nominal molecular weight cutoffs. Initial experiments
      were performed with purified samples of the supercoiled and linear isoforms, with
      the results used to identify appropriate conditions for plasmid separation.
      FINDINGS: Plasmid transmission increased with increasing filtrate flux due to
      elongation of the plasmids in the converging flow field. However, the flux
      dependence was different for each plasmid due to differences in the extent of
      branching of the twisted supercoiled DNA. This behavior provided a significant
      selectivity that could be used to separate the 3.0 and 16.8 kbp supercoiled
      plasmids using small pore size ultrafiltration membranes.

PMID- 27038284
TI  - Mesoporous polyacrylic acid supported silver nanoparticles as an efficient
      catalyst for reductive coupling of nitrobenzenes and alcohols using glycerol as
      hydrogen source.
AB  - Silver nanoparticle immobilized mesoporous cross-linked polyacrylic acid (Ag-MCP
      1) has been synthesized via aqueous-phase polymerization of acrylic acid followed
      by the surface immobilization with silver nanoparticles. The nanocomposite
      material has been characterized by different spectroscopic techniques. Powder X
      ray diffraction patterns revealed the formation of silver nanoparticles, while
      transmission electron microscope image showed that Ag nanoparticles are formed
      and uniformly dispersed in the mesoporous polyacrylic acid. The Ag-MCP-1
      nanocomposite can be used as an efficient heterogeneous catalyst in the reductive
      coupling of nitrobenzenes and alcohols using glycerol as hydrogen source. This
      nanocomposite can be reused more than five times without any significant decrease
      in its catalytic activity. 

PMID- 27038285
TI  - Glycine decarboxylase in C3, C4 and C3-C4 intermediate species.
AB  - The glycine decarboxylase complex (GDC) plays a central role in photorespiration.
      GDC is localized in the mitochondria and together with serine
      hydroxymethyltransferase it converts two molecules of glycine to one molecule of
      serine, CO2 and NH3. Overexpression of GDC subunits in the C3 species Arabidopsis
      thaliana can increase the metabolic flux through the photorespiratory pathway
      leading to enhanced photosynthetic efficiency and consequently to an enhanced
      biomass production of the transgenic plants. Changing the spatial expression
      patterns of GDC subunits was an important step during the evolution of C3-C4
      intermediate and likely also C4 plants. Restriction of the GDC activity to the
      bundle sheath cells led to the establishment of a photorespiratory CO2 pump.

PMID- 27038286
TI  - Benefit Sharing in a Global Context: Working Towards Solutions for
      Implementation.
AB  - Due to the state of globalized clinical research, questions have been raised as
      to what, if any, benefits those who contribute to research should receive. One
      model for compensating research participants is "benefit sharing," and the basic
      premise is that, as a matter of justice, those who contribute to scientific
      research should share in its benefits. While incorporated into several
      international documents for over two decades, benefit sharing has only been
      sparsely implemented. This analysis begins by addressing the concept of benefit
      sharing, its historical development, and how it has been applied in the context
      of virus sharing for influenza research. The second portion of this analysis
      presents recommendations for ensuring benefit sharing. These recommendations are
      threefold: 1) an emphasis on social pressure, 2) the revision of international
      documents as means to ensure benefit sharing, and 3) greater collaboration
      between sponsor IRB and host country IRB. Because clinical research is a
      globalized industry, a global model will be proposed in the second that focuses
      on collaboration between the sponsor and host country. This collaboration is
      vital in order to ensure that proper forms of benefit sharing are accomplished as
      a matter of justice.

PMID- 27038287
TI  - Deceleration Capacity of Heart Rate Predicts Arrhythmic and Total Mortality in
      Heart Failure Patients.
AB  - BACKGROUND: Deceleration capacity (DC) of heart rate proved an independent
      mortality predictor in postmyocardial infarction patients. The original method
      (DCorig) may produce negative values (9% in our analyzed sample). We aimed to
      improve the method and to investigate if DC also predicts the arrhythmic
      mortality. METHODS: Time series from 221 heart failure patients was analyzed with
      DCorig and a new variant, the DCsgn, in which decelerations are characterized
      based on windows of four consecutive beats and not on anchors. After 41.2 months,
      69 patients experienced sudden cardiac death (SCD) surrogate end points, while 61
      died. RESULTS: (SCD+ vs SCD-group) DCorig: 3.7 +/- 1.6 ms versus 4.6 +/- 2.6 ms
      (P = 0.020) and DCsgn: 4.9 +/- 1.7 ms versus 6.1 +/- 2.2 ms (P < 0.001). After
      Cox regression (gender, age, left ventricular ejection fraction, filtered QRS,
      NSVT>=1/24h, VPBs>=240/24h, mean 24-h QTc, and each DC index added on the model
      separately), DCsgn (continuous) was an independent SCD predictor (hazard ratio
      [H.R.]: 0.742, 95% confidence intervals (C.I.): 0.631-0.871, P < 0.001). DCsgn <=
      5.373 (dichotomous) presented 1.815 H.R. for SCD (95% C.I.: 1.080-3.049, P =
      0.024), areas under curves (AUC)/receiver operator characteristic (ROC): 0.62
      (DCorig) and 0.66 (DCsgn), P = 0.190 (chi-square). Results for deceased versus
      alive group: DCorig: 3.2 +/- 2.0 ms versus 4.8 +/- 2.4 ms (P < 0.001) and DCsgn:
      4.6 +/- 1.4 ms versus 6.2 +/- 2.2 ms (P < 0.001). In Cox regression, DCsgn
      (continuous) presented H.R.: 0.686 (95% C.I. 0.546-0.862, P = 0.001) and DCsgn <=
      5.373 (dichotomous) presented an H.R.: 2.443 for total mortality (TM) (95% C.I.
      1.269-4.703, P = 0.008). AUC/ROC: 0.71 (DCorig) and 0.73 (DCsgn), P = 0.402.
      CONCLUSIONS: DC predicts both SCD and TM. DCsgn avoids the negative values,
      improving the method in a nonstatistical important level.

PMID- 27038288
TI  - Hybrid Silver Mesh Electrode for ITO-Free Flexible Polymer Solar Cells with Good
      Mechanical Stability.
AB  - Herein, we report a tailored Ag mesh electrode coated with poly(3,4
      ethylenedioxythiophene) (PEDOT) polymer on a flexible polyethylene terephthalate
      (PET) substrate. The introduction of this highly conductive polymer solves the
      existing problems of Ag mesh-type transparent conductive electrodes, such as high
      pitch, roughness, current inhomogeneity, and adhesion problems between the Ag
      mesh grid and PEDOT polymer or PET substrate, to result in excellent electron
      spreading from the discrete Ag mesh onto the entire surface without sacrificing
      sheet conductivity and optical transparency. Based on this hybrid anode, we
      demonstrate highly efficient flexible polymer solar cells (PSCs) with a high fill
      factor of 67.11 %, which results in a power conversion efficiency (PCE) of 6.9 %
      based on a poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b'] dithiophene-2,6
      diyl}{3-fluoro-2-[(2-ethylhexyl) carbonyl]thieno[3,4-b]thiophenediyl}):[6,6]
      phenyl-C71 -butyric acid methyl ester bulk heterojunction device. Furthermore,
      the PSC device with the Ag mesh electrode also exhibits a good mechanical bending
      stability, as indicated by a 70 % retention of the initial PCE after 500 bending
      cycles compared with the PSC device with a PET/indium tin oxide electrode, which
      retained 0 % of the initial PCE after 300 bending cycles.

PMID- 27038289
TI  - A randomized clinical trial of prone position extubation to reduce the severity
      of coughing in patients undergoing dorsolumbar spine surgery.

PMID- 27038290
TI  - The relationship between study findings and publication outcome in anesthesia
      research: a retrospective observational study examining publication bias.
AB  - PURPOSE: Many areas of medicine have shown bias towards the publication of
      studies with positive results. To estimate publication bias in the anesthesia
      literature, we reviewed all abstracts presented at the American Society of
      Anesthesiologists (ASA) annual meetings over a four-year period and compared
      study results (positive vs negative) with publication outcomes. METHODS: This
      review included all abstracts from the 2001-2004 ASA annual meetings performed as
      randomized-controlled trials in humans. We scored their outcome results as
      positive or negative and assessed abstract quality using a 13-point scoring
      system. We then performed a systematic literature search to identify any
      subsequent publication of the studies and calculated the relative risk (RR) for
      journal publication by comparing positive vs negative studies. RESULTS: Of 5,918
      abstracts reviewed, 1,052 met inclusion criteria, and 564 (53.6%) of the
      abstracts proceeded to publication. The RR for abstracts with positive results
      proceeding to journal publication was 1.42 (95% confidence interval, 1.22 to
      1.66; P < 0.001). This result did not change significantly after adjusting for
      study size and abstract quality score during logistic regression modelling. There
      was no significant difference in the abstract quality score between positive vs
      negative studies or between abstracts proceeding vs not proceeding to
      publication. CONCLUSIONS: Approximately half of the ASA annual meeting abstracts
      proceed to publication. After adjustment for study quality and size, abstracts
      with positive results were more likely to proceed to journal publication than
      those with negative results, suggesting publication bias in the anesthesia
      literature.

PMID- 27038291
TI  - Efficient One-Step Production of Microencapsulated Hepatocyte Spheroids with
      Enhanced Functions.
AB  - Hepatocyte spheroids microencapsulated in hydrogels can contribute to liver
      research in various capacities. The conventional approach of microencapsulating
      spheroids produces a variable number of spheroids per microgel and requires an
      extra step of spheroid loading into the gel. Here, a microfluidics technology
      bypassing the step of spheroid loading and controlling the spheroid
      characteristics is reported. Double-emulsion droplets are used to generate
      microencapsulated homotypic or heterotypic hepatocyte spheroids (all as single
      spheroids <200 MUm in diameter) with enhanced functions in 4 h. The composition
      of the microgel is tunable as demonstrated by improved hepatocyte functions
      during 24 d culture (albumin secretion, urea secretion, and cytochrome P450
      activity) when alginate-collagen composite hydrogel is used instead of alginate.
      Hepatocyte spheroids in alginate-collagen also perform better than hepatocytes
      cultured in collagen-sandwich configuration. Moreover, hepatocyte functions are
      significantly enhanced when hepatocytes and endothelial progenitor cells (used as
      a novel supporting cell source) are co-cultured to form composite spheroids at an
      optimal ratio of 5:1, which could be further boosted when encapsulated in
      alginate-collagen. This microencapsulated-spheroid formation technology with high
      yield, versatility, and uniformity is envisioned to be an enabling technology for
      liver tissue engineering as well as biomanufacturing. 

PMID- 27038292
TI  - Serum brain-derived neurotrophic factor levels and sleep disorders in Chinese
      healthy and newly diagnosed type 2 diabetic subjects.
AB  - BACKGROUND: The aims of the present study were to detect serum brain-derived
      neurotrophic factor (BDNF) protein concentrations in healthy and diabetic
      subjects with sleep disorders and to explore correlations among serum BDNF
      concentrations, metabolic parameters and inflammation. METHODS: In all, 377
      eligible subjects were recruited to the study and underwent a 75-g oral glucose
      tolerance test. Various clinical parameters of metabolic disorders and cytokines
      were measured. Sleep disorders were assessed using the Pittsburgh Sleep Quality
      Index (PSQI). Subjects were grouped into those with normal glucose tolerance
      (NGT), those with NGT and sleep disorders (NGT-SDi), those with newly diagnosed
      type 2 diabetes mellitus (T2DM), and those with newly diagnosed T2DM and sleep
      disorders (T2DM-SDi). RESULTS: Serum BDNF levels were higher in the NGT-SDi and
      T2DM-SDi subgroups than in the NGT and T2DM groups, respectively. Multiple linear
      regression analysis revealed that serum BDNF concentrations were independently
      correlated with PSQI scores, homeostasis model assessment of insulin resistance,
      and HbA1c, interleukin 6 and tumor necrosis factor-alpha concentrations (P < 0.05
      for all). Binary logistic regression analysis revealed that significant
      associations remained between serum BDNF concentrations and sleep disorders after
      adjustment for glucose- and metabolic-related factors in both the NGT-SDi and
      T2DM-SDi subgroups. CONCLUSIONS: Serum BDNF concentrations were higher in
      patients with sleep disorders and were associated with various metabolic
      parameters and inflammatory cytokines.

PMID- 27038294
TI  - The retrotrapezoid nucleus as a central brainstem area for central and peripheral
      chemoreceptor interactions.

PMID- 27038293
TI  - Mucolipidosis III GNPTG Missense Mutations Cause Misfolding of the gamma Subunit
      of GlcNAc-1-Phosphotransferase.
AB  - The lysosomal storage disorder ML III gamma is caused by defects in the gamma
      subunit of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase,
      the enzyme that tags lysosomal enzymes with the mannose 6-phosphate lysosomal
      targeting signal. In patients with this disorder, most of the newly synthesized
      lysosomal enzymes are secreted rather than being sorted to lysosomes, resulting
      in increased levels of these enzymes in the plasma. Several missense mutations in
      GNPTG, the gene encoding the gamma subunit, have been reported in mucolipidosis
      III gamma patients. However, in most cases, the impact of these mutations on
      gamma subunit function has remained unclear. Here, we report that the variants
      c.316G>A (p.G106S), c.376G>A (p.G126S), and c.425G>A (p.C142Y) cause misfolding
      of the gamma subunit, whereas another variant, c.857C>T (p.T286M), does not
      appear to alter gamma subunit function. The misfolded gamma subunits were
      retained in the ER and failed to rescue the lysosomal targeting of lysosomal acid
      glycosidases.

PMID- 27038295
TI  - Gastrorenal communication: sniffing and tasting.
AB  - A video slideshow introduction to the Symposium by organiser Pedro A. Jose can be
      found here. 

PMID- 27038297
TI  - Letter regarding article: 'Effect of acute exercise on circulating angiogenic
      cell and microparticle populations'.

PMID- 27038296
TI  - Deletion of Kvbeta1.1 subunit leads to electrical and haemodynamic changes
      causing cardiac hypertrophy in female murine hearts.
AB  - NEW FINDINGS: What is the central question of this study? The goal of this study
      was to evaluate sex differences and the role of the potassium channel beta1
      (Kvbeta1) subunit in the heart. What is the main finding and its importance?
      Genetic ablation of Kvbeta1.1 in females led to cardiac hypertrophy characterized
      by increased heart size, prolonged monophasic action potentials, elevated blood
      pressure and increased myosin heavy chain alpha (MHCalpha) expression. In
      contrast, male mice showed only electrical changes. Kvbeta1.1 binds the MHCalpha
      isoform at the protein level, and small interfering RNA targeted knockdown of
      Kvbeta1.1 upregulated MHCalpha. Cardiovascular disease is the leading cause of
      death and debility in women in the USA, and cardiac arrhythmias are a major
      concern. Voltage-gated potassium (Kv) channels along with the binding partners;
      Kvbeta subunits are major regulators of the action potential (AP) shape and
      duration (APD). The regulation of Kv channels by the Kvbeta1 subunit is unknown
      in female hearts. In the present study, we hypothesized that the Kvbeta1 subunit
      is an important regulator of female cardiac physiology. To test this hypothesis,
      we ablated (knocked out; KO) the KCNAB1 isoform 1 (Kvbeta1.1) subunit in mice and
      evaluated cardiac function and electrical activity by using ECG, monophasic
      action potential recordings and echocardiography. Our results showed that the
      female Kvbeta1.1 KO mice developed cardiac hypertrophy, and the hearts were
      structurally different, with enlargement and increased area. The electrical
      derangements caused by Kvbeta1.1 KO in female mice included long QTc and QRS
      intervals along with increased APD (APD20-90% repolarization). The male Kvbeta1.1
      KO mice did not develop cardiac hypertrophy, but they showed long QTc and
      prolonged APD. Molecular analysis showed that several genes that support cardiac
      hypertrophy were significantly altered in Kvbeta1.1 KO female hearts. In
      particular, myosin heavy chain alpha expression was significantly elevated in
      Kvbeta1.1 KO mouse heart. Using a small interfering RNA strategy, we identified
      that knockdown of Kvbeta1 increases myosin heavy chain alpha expression in H9C2
      cells. Collectively, changes in molecular and cell signalling pathways clearly
      point towards a distinct electrical and structural remodelling consistent with
      cardiac hypertrophy in the Kvbeta1.1 KO female mice.

PMID- 27038298
TI  - Injuries in Swedish floorball: a cost analysis.
AB  - The epidemiology of sport injuries is well documented. However, the costs are
      rarely discussed. Previous studies have presented such costs in specific sports
      or localization. No study has investigated the costs related to injuries in elite
      floorball. Thus, the aim of this study was to estimate cost of injuries in
      Swedish elite floorball players. During 1 year, 346 floorball players were
      prospectively followed. All time-loss injures were recorded. The injured players
      were asked to complete a questionnaire regarding their costs tied to the injury.
      Mean costs were calculated by multiplying the total resource use with the
      collected unit costs and dividing these total costs with the number of injuries
      as well as players. The results showed that the average cost per injury increased
      with the level of severity and ranged from 332 to 2358 Euros. The mild and
      moderate overuse injuries were costlier than the corresponding traumatic
      injuries. However, the severe traumatic injuries were associated with higher
      costs than overuse injuries. Knee injuries were the costliest. Our results
      indicate that there are costs to be saved, if floorball injuries can be avoided.
      They should be of interest to decision makers deciding whether to invest in
      preventive interventions.

PMID- 27038299
TI  - Practice recommendations: A new type of article in Pediatric Transplantation.

PMID- 27038300
TI  - Liver transplantation for maple syrup urine disease: A global domino effect.

PMID- 27038301
TI  - Polyomaviruses BK, JC, KI, WU, MC, and TS in children with allogeneic
      hematopoietic stem cell transplantation.
AB  - Timely and reliable detection of viruses is of key importance in early diagnosis
      of infection(s) following allogeneic HSCT. Among the immunocompetent, infections
      with BKPyV and JCPyV are mostly subclinical, while post-HSCT, the former may
      cause HC and the latter PML. The epidemiology and clinical impact of the newly
      identified KIPyV, WUPyV, MCPyV, and TSPyV in this context remain to be defined.
      To assess the incidence and clinical impact of BKPyV, JCPyV, KIPyV, WUPyV, MCPyV,
      and TSPyV infections, we performed longitudinal molecular surveillance for
      DNAemias of these HPyVs among 53 pediatric HSCT recipients. Surveillance pre-HSCT
      and for three months post-HSCT revealed BKPyV DNAemia in 20 (38%) patients. Our
      data demonstrate frequent BKPyV DNAemia among pediatric patients with HSCT and
      the confinement of clinical symptoms to high copy numbers alone. MCPyV and JCPyV
      viremias occurred at low and TSPyV viremia at very low prevalences. KIPyV or
      WUPyV viremias were not demonstrable in this group of immunocompromised patients.

PMID- 27038302
TI  - Comparing biomarkers as trial level general surrogates.
AB  - An intermediate response measure that accurately predicts efficacy in a new
      setting can reduce trial cost and time to product licensure. In this article, we
      define a trial level general surrogate, which is an intermediate response that
      can be used to accurately predict efficacy in a new setting. Methods for
      evaluating general surrogates have been developed previously. Many methods in the
      literature use trial level intermediate responses for prediction. However, all
      existing methods focus on surrogate evaluation and prediction in new settings,
      rather than comparison of candidate general surrogates, and few formalize the use
      of cross validation to quantify the expected prediction error. Our proposed
      method uses Bayesian non-parametric modeling and cross-validation to estimate the
      absolute prediction error for use in evaluating and comparing candidate trial
      level general surrogates. Simulations show that our method performs well across a
      variety of scenarios. We use our method to evaluate and to compare candidate
      trial level general surrogates in several multi-national trials of a pentavalent
      rotavirus vaccine. We identify at least one immune measure that has potential
      value as a trial level general surrogate and use it to predict efficacy in a new
      trial where the clinical outcome was not measured.

PMID- 27038303
TI  - Adaptation and Diversification of an RNA Replication System under Initiation- or
      Termination-Impaired Translational Conditions.
AB  - Adaptation to various environments is a remarkable characteristic of life. Is
      this limited to extant complex living organisms, or is it also possible for a
      simpler self-replication system to adapt? In this study, we addressed this
      question by using a translation-coupled RNA replication system that comprised a
      reconstituted translation system and an RNA "genome" that encoded a replicase
      gene. We performed RNA replication reactions under four conditions, under which
      different components of translation were partly inhibited. We found that
      replication efficiency increased with the number of rounds of replication under
      all the tested conditions. The types of dominant mutations differed depending on
      the condition, thus indicating that this simple system adapted to different
      environments in different ways. This suggests that even a primitive self
      replication system composed of a small number of genes on the early earth could
      have had the ability to adapt to various environments.

PMID- 27038304
TI  - Red, Yellow, Blue and Green Emission from Eu(3+), Dy(3+) and Bi(3+) Doped
      Y2O3nano-Phosphors.
AB  - Rare earth elements (RE = Eu(3+)& Dy(3+))and Bi(3+) doped Y2O3 nanoparticles were
      synthesized by urea hydrolysis method in ethylene glycol, which acts as reaction
      medium as well as a capping agent, at a low temperature of 140  degrees
      C,followed by calcination of the obtained product. Transmission electron
      microscope (TEM) images reveals that ovoid shaped Y2O3 nanoparticles of around 22
      24 nm size range were obtained in this method. The respective RE and Bi(3+) doped
      Y2O3 precursor nanoparticles when heated at 600 and 750  degrees C, retains the
      same shape as that of the as-synthesized Y2O3 precursor samples. From EDAX
      spectra, the incorporation of RE ions into the host has been studied. XRD pattern
      reveals the crystalline nature of the heated nanoparticles and indicate the
      absence of any impurity phase other than cubic Y2O3.However, the as-synthesized
      nanoparticles were highly amorphous without the presence of any sharp XRD peaks.
      Photoluminescence study suggests that the synthesized samples could be used as
      red (Eu(3+)), yellow (Dy(3+)), blue and green (Bi(3+))emitting phosphors. 

PMID- 27038305
TI  - Migration by seed dispersal of ACCase-inhibitor-resistant Avena fatua in north
      western Mexico.
AB  - BACKGROUND: Biotypes of Avena fatua resistant to ACCase-inhibiting herbicides
      have been reported in the States of Baja California (BC) and Sonora (SON),
      Mexico. We hypothesised that resistant biotypes present in SON (Valle de
      Hermosillo and Valle del Yaqui) are derived from a resistant population from BC
      (Valle de Mexicali) via gene flow through the transport and exchange of
      contaminated wheat seed. This study aimed to determine (1) the resistance of A.
      fatua to ACCase-inhibiting herbicides in populations from BC and SON, (2) the
      mutation at the site of action and (3) the genetic structure and gene flow among
      populations. RESULTS: DNA sequencing showed that all biotypes shared the same
      mutation (Leu * Ile at codon 1781). Microsatellites showed evidence of a genetic
      bottleneck in SON, and spatial analysis of molecular variance grouped one biotype
      from the Valle de Mexicali with two biotypes from the Valle de Hermosillo.
      Migration analysis suggested gene flow from the Valle de Mexicali to the Valle de
      Hermosillo, but not to the Valle del Yaqui. CONCLUSIONS: The presence of
      resistant biotypes of A. fatua in the Valle de Hermosillo, SON, are likely
      derived from seeds from BC, possibly through the transport of contaminated wheat
      seeds. (c) 2016 Society of Chemical Industry.

PMID- 27038307
TI  - Association analysis of psoriasis vulgaris and psoriatic arthritis with loss-of
      function mutations in IL36RN in German patients.

PMID- 27038306
TI  - Nonsurgical treatment and early return to activity leads to improved Achilles
      tendon fatigue mechanics and functional outcomes during early healing in an
      animal model.
AB  - Achilles tendon ruptures are common and devastating injuries; however, an
      optimized treatment and rehabilitation protocol has yet to be defined. Therefore,
      the objective of this study was to investigate the effects of surgical repair and
      return to activity on joint function and Achilles tendon properties after 3 weeks
      of healing. Sprague-Dawley rats (N = 100) received unilateral blunt transection
      of their Achilles tendon. Animals were then randomized into repaired or non
      repaired treatments, and further randomized into groups that returned to activity
      after 1 week (RTA1) or after 3 weeks (RTA3) of limb casting in plantarflexion.
      Limb function, passive joint mechanics, and tendon properties (mechanical,
      organizational using high frequency ultrasound, histological, and compositional)
      were evaluated. Results showed that both treatment and return to activity
      collectively affected limb function, passive joint mechanics, and tendon
      properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight
      bearing of the injured limb compared to RTA3 animals 3-weeks post-injury. Such
      functional improvements in RTA1 tendons were evidenced in their mechanical
      fatigue properties and increased cross sectional area compared to RTA3 tendons.
      When RTA1 was coupled with nonsurgical treatment, superior fatigue properties
      were achieved compared to repaired tendons. No differences in cell shape,
      cellularity, GAG, collagen type I, or TGF-beta staining were identified between
      groups, but collagen type III was elevated in RTA3 repaired tendons. The larger
      tissue area and increased fatigue resistance created in RTA1 tendons may prove
      critical for optimized outcomes in early Achilles tendon healing following
      complete rupture. (c) 2016 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 34:2172-2180, 2016.

PMID- 27038308
TI  - Development and validation of a custom microarray for global transcriptome
      profiling of the fungus Aspergillus nidulans.
AB  - Transcriptome profiling is a powerful tool for identifying gene networks from
      whole genome expression analysis in many living species. Here is described the
      first extensively characterized platform using Agilent microarray technology for
      transcriptome analysis in the filamentous fungus Aspergillus (Emericella)
      nidulans. We developed and validated a reliable gene expression microarray in 8 *
      15 K format, with predictive and experimental data establishing its specificity
      and sensitivity. Either one or two 60-mer oligonucleotide probes were selected
      for each of 10,550 nuclear as well as 20 mitochondrial coding sequences. More
      than 99 % of probes were predicted to hybridize with 100 % identity to their
      aimed specific A. nidulans target only. Probe sensitivity was supported by a
      highly narrow distribution of melting temperatures together with thermodynamic
      features, which strongly favored probe-target perfect match hybridization, in
      comparison with predicted secondary structures. Array quality was evaluated
      through transcriptome comparison of two A. nidulans strains, differing by the
      presence or not of Escherichia coli LacZ transgene. High signal-to-noise ratios
      were measured, and signal reproducibility was established at intra-probe and
      inter-probe levels. Reproducibility of microarray performances was assessed by
      high correlation between two-color dye signals and between technical replicates.
      Results were confirmed by RT-qPCR analysis on five genes. Though it covers 100 %
      of the A. nidulans targeted coding sequences, this low density array allows
      limited experimental costs and simplified data analysis process, making it
      suitable for studying gene expression in this model organism through large
      numbers of experimental conditions, in basic, biomedical or industrial
      microbiology research fields.

PMID- 27038309
TI  - Declining water yield from forested mountain watersheds in response to climate
      change and forest mesophication.
AB  - Climate change and forest disturbances are threatening the ability of forested
      mountain watersheds to provide the clean, reliable, and abundant fresh water
      necessary to support aquatic ecosystems and a growing human population. Here, we
      used 76 years of water yield, climate, and field plot vegetation measurements in
      six unmanaged, reference watersheds in the southern Appalachian Mountains of
      North Carolina, USA to determine whether water yield has changed over time, and
      to examine and attribute the causal mechanisms of change. We found that annual
      water yield increased in some watersheds from 1938 to the mid-1970s by as much as
      55%, but this was followed by decreases up to 22% by 2013. Changes in forest
      evapotranspiration were consistent with, but opposite in direction to the changes
      in water yield, with decreases in evapotranspiration up to 31% by the mid-1970s
      followed by increases up to 29% until 2013. Vegetation survey data showed
      commensurate reductions in forest basal area until the mid-1970s and increases
      since that time accompanied by a shift in dominance from xerophytic oak and
      hickory species to several mesophytic species (i.e., mesophication) that use
      relatively more water. These changes in forest structure and species composition
      may have decreased water yield by as much as 18% in a given year since the mid
      1970s after accounting for climate. Our results suggest that changes in climate
      and forest structure and species composition in unmanaged forests brought about
      by disturbance and natural community dynamics over time can result in large
      changes in water supply.

PMID- 27038310
TI  - Variation in strategy use across measures of verbal working memory.
AB  - The working memory (WM) literature contains a number of tasks that vary on
      dimensions such as when or how memory items are reported. In addition to the ways
      in which WM tasks are designed to differ, tasks may also diverge according to the
      strategies participants use during task performance. The present study included
      seven tasks from the WM literature, each requiring short-term retention of verbal
      items. Following completion of a small number of trials from each task,
      individuals completed a self-report questionnaire to identify their primary
      strategy. Results indicated substantial variation across individuals for a given
      task, and within the same individual across tasks. Moreover, while direct
      comparisons between tasks showed that some tasks evinced similar patterns of
      strategy use despite differing task demands, others showed markedly different
      patterns of self-reported strategy use. A community detection algorithm, aimed at
      identifying groups of individuals based on their profile of strategic choices,
      revealed unique communities of individuals who are dependent on specific
      strategies under varying demands. Together, the findings suggest that researchers
      using common WM paradigms should very carefully consider the implications of
      variation in strategy use when interpreting their findings.

PMID- 27038311
TI  - Upregulation of 3-MST Relates to Neuronal Autophagy After Traumatic Brain Injury
      in Mice.
AB  - 3-mercaptopyruvate sulfurtransferase (3-MST) was a novel hydrogen sulfide (H2S)
      synthesizing enzyme that may be involved in cyanide degradation and in
      thiosulfate biosynthesis. Over recent years, considerable attention has been
      focused on the biochemistry and molecular biology of H2S-synthesizing enzyme. In
      contrast, there have been few concerted attempts to investigate the changes in
      the expression of the H2S-synthesizing enzymes with disease states. To
      investigate the changes of 3-MST after traumatic brain injury (TBI) and its
      possible role, mice TBI model was established by controlled cortical impact
      system, and the expression and cellular localization of 3-MST after TBI was
      investigated in the present study. Western blot analysis revealed that 3-MST was
      present in normal mice brain cortex. It gradually increased, reached a peak on
      the first day after TBI, and then reached a valley on the third day. Importantly,
      3-MST was colocalized with neuron. In addition, Western blot detection showed
      that the first day post injury was also the autophagic peak indicated by the
      elevated expression of LC3. Importantly, immunohistochemistry analysis revealed
      that injury-induced expression of 3-MST was partly colabeled by LC3. However,
      there was no colocalization of 3-MST with propidium iodide (cell death marker)
      and LC3 positive cells were partly colocalized with propidium iodide. These data
      suggested that 3-MST was mainly located in living neurons and may be implicated
      in the autophagy of neuron and involved in the pathophysiology of brain after
      TBI.

PMID- 27038312
TI  - Meningitis Caused by Candida Dubliniensis in a Patient with Cirrhosis: A Case
      Report and Review of the Literature.
AB  - Candida species, including Candida dubliniensis, are a rare cause of meningitis.
      Herein, we report the second case of C. dubliniensis meningitis in a 49-year-old
      man with a history of hepatitis C virus-related cirrhosis, substance use
      disorder, and recent exposure to intravenous antibiotic therapy, presenting with
      confusion, abnormal gait, and urinary incontinence. Magnetic resonance imaging
      (MRI) of the brain showed marked hydrocephalus and leptomeningeal enhancement.
      Initial cerebrospinal fluid (CSF) studies were concerning for bacterial
      meningitis, although cultures were negative. Despite empiric treatment with broad
      spectrum antibiotics, the patient's mental status declined. The diagnosis of C.
      dubliniensis meningitis was not made until the third lumbar puncture. The patient
      was treated with liposomal amphotericin B and flucytosine. Despite improvement of
      hydrocephalus on MRI of the brain and sterilization of CSF, the patient's mental
      status declined and he expired. This case highlights the difficulty in the
      diagnosis of C. dubliniensis meningitis as multiple lumbar punctures may be
      necessary. C. dubliniensis meningitis should be considered in the differential
      diagnosis for a patient with risk factors such as end-stage liver disease, human
      immunodeficiency virus infection, recent chemotherapy, substance use disorders,
      and recent broad-spectrum antibiotic use. A high index of suspicion is necessary
      as delay in initiation of therapy is associated with high mortality. The optimal
      treatment strategy has not been determined. 

PMID- 27038313
TI  - The efficacy of open partial aponeurectomy for recurrent Dupuytren's contracture.
AB  - INTRODUCTION: To evaluate the efficacy of open partial aponeurectomy for
      recurrent Dupuytren's contracture. METHODS: Eighteen patients with recurrent
      Dupuytren's contracture of 22 fingers were retrospectively assessed with a mean
      follow-up time of 94 months (range: 70-114 months). Examination parameters
      included the determination of range of motion (ROM), grip strength, pain and
      subjective outcome (disabilities of the arm, shoulder and hand (DASH)
      questionnaire). SURGICAL TECHNIQUE: Dissection with special regard to former skin
      incision and expected wound defect. Modified incisions after Bruner (Mini-Bruner
      incisions) were facilitated. Dissection started at the palm. Fibrous tissue was
      resected proximally within the palm including vertical fibrotic septae. Direct
      preparation of the neurovascular bundles (NVB) was facilitated from proximal to
      distal. If the anatomy of the neurovascular structures became unclear around the
      natatory ligament preparation of the NVB at the distal end of the fibrous cord
      was performed. After complete preparation of a NVB, dissection was continued from
      medial to lateral until the other bundle was completely released. Transposition
      flaps and skin transplants were often used for sufficient wound closure. RESULTS:
      Recurrence rate was 36 % applying the definition of van Rijssen et al. Fifteen
      patients had a grip strength of 90 % or higher in comparison to the contralateral
      side. Ten patients had a pinch strength of 90 % or higher in comparison to the
      contralateral side. All patients except for one had pain reduction or none
      postoperatively. Fifteen patients had a DASH score of 15 or lower (range: 0-47).
      An unrelated ray amputation was suffered due to wound healing complications.
      CONCLUSIONS: Open partial aponeurectomy performed by a board certified hand
      surgeon proved to be safe. The postoperative functional outcome seemed to be
      related to the individual course of the disease.

PMID- 27038314
TI  - [Not Available].

PMID- 27038315
TI  - Major motor-functional determinants associated with poor self-reported health
      related quality of life in myasthenia gravis patients.
AB  - Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which disabling
      muscle weakness may affect health-related quality of life (HRQoL). The aim of
      this study was to investigate which common motor-functional deficits and
      corresponding severity are most determinant of poor HRQoL in these patients. In
      41 patients, the dichotomized first item of the Italian Myasthenia Gravis
      Questionnaire (IMGQ), categorizing patients who report "good" and "poor" HRQoL,
      was chosen as dependent-outcome variable. All items composing the myasthenia
      gravis-specific scale (MG-ADL), i.e. talking, chewing, swallowing, breathing,
      impairment of ability to brush teeth or comb hair, impairment of ability to rise
      from chair, double vision, and eyelid droop were acquired as independent
      variables and dichotomized. Stepwise backward LR multivariable logistic
      regression analysis was performed. In addition, the main characteristics of
      patients were compared. MG-ADL items "chewing" >=1, i.e. "fatigue chewing solid
      food", and "breathing" >=2, i.e. "shortness of breath at rest" proved to be
      significant determinants. Higher dose of corticosteroid therapy was significantly
      (p = 0.027; r s  = -0.35), correlated with poor HRQoL. At diagnosis, a
      decremental response to repetitive nerve stimulation (RNS) from the abductor
      pollicis brevis was significantly more frequent in patients with poor HRQoL. In
      conclusion, impaired "chewing" and "breathing" functions indicate the need for
      careful planning of rehabilitation, re-education and patient management.
      Moreover, decremental response to RNS at diagnosis may identify patients at risk
      for poor HRQoL. 

PMID- 27038316
TI  - Biodistribution of [(68)Ga]PSMA-HBED-CC in Patients with Prostate Cancer:
      Characterization of Uptake in Normal Organs and Tumour Lesions.
AB  - PURPOSE: The aim of this study was to determine the physiological and
      pathophysiological biodistribution of [(68)Ga]PSMA-HBED-CC (PSMA-11)
      ([(68)Ga]PSMA) in patients with prostate cancer (PCA) to establish the range of
      normal uptake in relevant organs and primary prostate tumours, locally recurrent
      PCA, lymph and bone metastases and other metastatic lesions. Additionally, we
      aimed to determine a cut-off uptake value for differentiation of primary tumours
      from normal prostate tissue. PROCEDURES: Overall, [(68)Ga]PSMA positron emission
      tomography/x-ray computed tomography (PET/CT) of 101 patients (mean age 69.1
      years) with PCA was analysed retrospectively. For assessment of tracer
      biodistribution, maximum standardized uptake values (SUVmax) were calculated for
      various normal organs, as well as for primary tumours (PT) and/or metastases.
      Results are presented as median, interquartile range (IQR; 25th quantil-75th
      quantil) and range (minimum-maximum). RESULTS: [(68)Ga]PSMA PET/CT was performed
      50 min (range 30-126) after injection of 109 MBq (range 84-158). Regarding
      biodistribution, highest uptake (median/IQR/range) of the tracer was found in the
      kidneys (49.6/40.7-57.6/2.7-97.0) followed by the submandibular glands (17.3/13.7
      21.2/7.5-30.4), parotid glands (16.1/12.2-19.8/5.5-30.9) and duodenum (13.8/10.5
      17.2/5.8-26.9). The best cut-off value for differentiating physiological uptake
      in the primary tumour from that in the prostate was found to be an SUVmax of 3.2.
      The median SUVmax in the PT (n = 35), locally recurrent PCA (n = 8), lymph node
      (n = 166), bone (n = 157) and other metastases (n = 3) were 10.2, 5.9, 6.2, 7.4
      and 3.8, respectively. The best cut-off values for differentiating non
      pathological uptake in lymph nodes and bones from tumour uptake were found to be
      SUVmax of 3.2 and 1.9, respectively. Patients with PSA <2 had significantly lower
      SUVmax in bone metastases as compared to patients with PSA >=2 (p < 0.01).
      CONCLUSIONS: This biodistribution study provided a broad range of uptake data of
      [(68)Ga]PSMA-11 for normal organs/tissues, primary prostate tumours and
      metastatic lesions based on a large patient cohort. Both PT and small metastatic
      lesions were detectable due to their high tracer uptake. Four-times-higher median
      uptake in PT in comparison to normal prostate stroma resulted in a high
      diagnostic accuracy that could potentially be used for multimodal image-guided
      biopsy with dedicated reconstruction software.

PMID- 27038317
TI  - Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin
      surges in ovariectomized rats.
AB  - Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy
      maintenance, lactation, and aspects of maternal behavior. In rodents, there is a
      surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of
      prolactin surges during early pregnancy, with a diurnal and nocturnal surge every
      day. Both of these patterns can be replicated in ovariectomized rats. A prior
      study demonstrated that central antagonism of kappa-opioid receptors, the target
      of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats.
      We build on this to determine whether dynorphin, perhaps from the arcuate
      population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy
      neurons), also contributes to the estradiol- or cervical stimulation-induced
      surges in ovariectomized rats. Ovariectomized rats were treated with either
      estradiol or cervical stimulation to induce prolactin surge(s). Blood samples
      were taken around the expected surge time to determine the effect of either acute
      kappa-opioid receptor antagonism or previous chemical ablation of the KNDy
      population on prolactin levels. Dynorphin antagonism does significantly disrupt
      the nocturnal prolactin surge, but it does not contribute to the estradiol
      induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation
      of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while
      a somewhat larger ablation significantly reduced the size of the estradiol
      induced surge. We conclude that dynorphin is likely a controlling factor for the
      nocturnal surge induced by cervical stimulation, and that other KNDy neuron
      products must play a role in the estradiol-induced surge. 

PMID- 27038319
TI  - How Good is Our Best Guess? Clinical Application of the WHO FRAX Tool in
      Osteoporotic Fracture Risk Determination and Treatment Decisions.
AB  - Historically, treatment decisions for osteoporosis were based on bone mineral
      density. However, many fractures occur in patients with T-scores outside the
      osteoporotic range, emphasizing the importance of multi-factorial risk
      assessments. The World Health Organization Fracture Risk Assessment Tool (FRAX)
      predicts 10-year risk of osteoporotic fracture. We hypothesized that physicians'
      clinical estimates of osteoporotic fracture risk would differ significantly from
      that calculated by FRAX. Thus, treatment decisions would differ depending whether
      or not physicians used FRAX. A survey consisting of five clinical scenarios was
      administered to 76 endocrinologists, family physicians, internists, and internal
      medicine residents. They were asked to estimate the osteoporotic fracture risk
      and decide whether they would offer preventative treatment. Their estimates were
      compared to the risk predicted by FRAX and national treatment threshold
      guidelines. The primary outcome was the difference between the participant's
      estimate and the FRAX-based estimate of the 10-year risk of osteoporotic fracture
      for each scenario. In each scenario, physicians statistically significantly over
      estimated fracture risk compared to that predicted by FRAX. Estimates for hip
      fracture risk were 2-4 times higher than FRAX estimates. The major osteoporotic
      fracture risk at which participants would offer treatment varied with physician
      group, with endocrinologists, family physicians, and residents requiring a 10-20
      % 10-year risk, while internal medicine physician thresholds ranged from 2 to 20
      %. Physicians greatly over-estimated the risk of hip fracture based on clinical
      information. FRAX is necessary to accurately quantify risk, but because
      physicians varied in the level of risk required before they would offer
      treatment, uniform approaches to risk estimation may still not result in uniform
      clinical treatment decisions.

PMID- 27038318
TI  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome:
      insights on insulin resistance, inflammation, and atherogenic dyslipidemia.
AB  - Low-density lipoprotein (LDL) cholesterol plays a pivotal role in the
      pathogenesis of atherosclerotic cardiovascular disease (CVD). The discovery that
      proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a key regulator
      pathway for hepatic LDL receptor (LDLR) degradation sheds light on new uncovered
      issues regarding LDL-C homeostasis. Indeed, as confirmed by phase II and III
      clinical trials with monoclonal antibodies, targeting PCSK9 represents the newest
      and most promising pharmacological tool for the treatment of hypercholesterolemia
      and related CVD. However, clinical, genetic, and experimental evidence indicates
      that PCSK9 may be either a cause or an effect in the context of metabolic
      syndrome (MetS), a condition comprising a cluster of risk factors including
      insulin resistance, obesity, hypertension, and atherogenic dyslipidemia. The
      latter is characterized by a triad of hypertriglyceridemia, low plasma
      concentrations of high-density lipoproteins, and qualitative changes in LDLs.
      PCSK9 levels seem to correlate with many of these lipid parameters as well as
      with the insulin sensitivity indices, although the molecular mechanisms behind
      this association are still unknown or not completely elucidated. Nevertheless,
      this area of research represents an important starting point for a better
      understanding of the physiological role of PCSK9, also considering the recent
      approval of new therapies involving anti-PCSK9. Thus, in the present review, we
      will discuss the current knowledge on the role of PCSK9 in the context of MetS,
      alteration of lipids, glucose homeostasis, and inflammation.

PMID- 27038320
TI  - Stress at work: Differential experiences of high versus low SES workers.
AB  - This paper asks whether workers with higher socioeconomic status (SES) experience
      different levels of stress at work than workers with lower SES and, if so, what
      might explain these differences. We collected innovative assessments of immediate
      objective and subjective measures of stress at multiple time points across
      consecutive days from 122 employed men and women. We find that in comparison to
      higher SES individuals, those with lower SES reported greater happiness at work,
      less self-reported stress, and less perceived stress; cortisol, a biological
      marker of stress, was unrelated to SES. Worker's momentary perceptions of the
      workplace were predicted by SES, with higher SES individuals more commonly
      reporting feeling unable to meet work demands, fewer work resources, and less
      positive work appraisals. In turn, perceptions of the workplace had a generally
      consistent and robust effect on positive mood, subjective stress, and cortisol. 

PMID- 27038322
TI  - Increasing public support for food-industry related, obesity prevention policies:
      The role of a taste-engineering frame and contextualized values.
AB  - BACKGROUND: Support for policies to combat obesity is often undermined by a
      public sense that obesity is largely a matter of personal responsibility.
      Industry rhetoric is a major contributor to this perception, as the soda/fast
      food/big food companies emphasize choice and individual agency in their efforts
      to neutralize policies that are burdensome. Yet obesity experts recognize that
      environmental forces play a major role in obesity. We investigate whether
      exposure to a taste-engineering frame increases support for food and beverage
      policies that address obesity. A taste-engineering frame details strategies used
      by the food industry to engineer preferences and increase the over-consumption of
      processed foods and sugary beverages. We also examine the effects of exposure to
      two contextualized values that have recently been promoted in expert discourse
      consumer knowledge and consumer safety - on public support of policies. Our
      research shows how causal frames and contextualized values may effectively
      produce support for new obesity policies. METHODS: We use an online survey
      experiment to test the effects of exposure to a taste-engineering frame (TEF),
      the value of consumer knowledge (CK), or the value of consumer safety (CS), on
      level of support for a range of policies. A random sample of adults, age 18 +
      living in the United States was included in the study (N = 2580). Ordered
      logistic regression was used to measure the effects of treatment exposure. The
      primary outcome was level-of-support for four (4) food-industry related, obesity
      prevention policies (aka food and beverage policies): 1) require food
      manufacturers to disclose the amount of additives in food products on food
      packaging; 2) require food-manufacturers to advertise food products in accordance
      with their actual nutritional value; 3) prohibit all high-fat, high-sugar food
      advertising on television programming watched primarily by children; and 4)
      increase healthy food availability in work sites, schools, and hospitals.
      FINDINGS: These data suggest that a taste-engineering frame and contextualized
      values significantly increase public support for many of the food and beverage
      policies tested. CONCLUSIONS: Applying a taste-engineering frame and/or
      contextualized values to address obesity advances a population-based policy
      agenda to counteract the effects of food-industry strategies.

PMID- 27038321
TI  - Discrimination and excessive weight gain during pregnancy among Black and Latina
      young women.
AB  - RATIONALE: Excessive weight gain during pregnancy is a major determinant of later
      life obesity among both Black and Latina women and their offspring. However,
      psychosocial determinants of this risk, including everyday discrimination, and
      potential moderators of such effects remain unexplored. OBJECTIVE: We examined
      the influence of discrimination, a culturally relevant stressor, on odds of
      gaining weight beyond Institute of Medicine recommendations during pregnancy.
      Whether the effect was moderated by race/ethnicity, age, or depressive symptoms
      was also examined. METHOD: Participants were 413 Black and Latina pregnant young
      women, ages 14-21 years. Experience with discrimination and all moderators were
      assessed in the second trimester. Last weight recorded in the third trimester was
      abstracted from medical records and used to determine excessive weight gain.
      RESULTS: Ever experiencing discrimination was associated with a 71% increase in
      the odds of excessive weight gain. The effect of discrimination was primarily
      present among women who attributed this treatment to membership in a historically
      oppressed group (e.g., ethnic minority, female) or to membership in other
      stigmatized groups (e.g., overweight). The effect of ever experiencing
      discrimination was not moderated by race/ethnicity or age but was moderated by
      depressive symptoms. Supporting the perspective of the environmental affordances
      model, discrimination strongly predicted excessive weight gain when women were
      low in depressive symptoms but had no effect when women were high in depressive
      symptoms. The moderating role of depressive symptoms was equivalent for Black and
      Latina women. CONCLUSION: Results highlight the role of discrimination in
      perpetuating weight-related health disparities and suggest opportunities for
      improving health outcomes among young pregnant women.

PMID- 27038323
TI  - PDE4B as a microglia target to reduce neuroinflammation.
AB  - The importance of microglia in immune homeostasis within the brain is undisputed.
      Their role in a diversity of neurological and psychiatric diseases as well as CNS
      injury is the subject of much investigation. Cyclic adenosine monophosphate (AMP)
      is a critical regulator of microglia homeostasis; as the predominant negative
      modulator of cyclic AMP signaling within microglia, phosphodiesterase 4 (PDE4)
      represents a promising target for modulating immune function. PDE4 expression is
      regulated by inflammation, and in turn, PDE4 inhibition can alter microglia
      reactivity. As the prototypic PDE4 inhibitor, rolipram, was tested clinically in
      the 1980s, drug discovery and clinical development of PDE4 inhibitors have been
      severely hampered by tolerability issues involving nausea and emesis. The two
      PDE4 inhibitors approved for peripheral inflammatory disorders (roflumilast and
      apremilast) lack brain penetration and are dose-limited by side effects making
      them unsuitable for modulating microglial function. Subtype selective inhibitors
      targeting PDE4B are of high interest given the critical role PDE4B plays in
      immune function versus the association of PDE4D with nausea and emesis. The
      challenges and requirements for successful development of a novel brain-penetrant
      PDE4B inhibitor are discussed in the context of early clinical development
      strategies. Furthermore, the challenges of monitoring the state of microglia in
      vivo are highlighted, including a description of the currently available tools
      and their limitations. Continued drug discovery efforts to identify safe and well
      tolerated, brain-penetrant PDE4 inhibitors are a reflection of the confidence in
      the rationale for modulation of this target to produce meaningful therapeutic
      benefit in a wide range of neurological conditions and injury. GLIA 2016;64:1698
      1709.

PMID- 27038324
TI  - Nutritional aspects of Noonan syndrome and Noonan-related disorders.
AB  - Rasopathies are a group of rare disorders characterized by
      neurocardiofaciocutaneous involvement, and caused by mutations in several genes
      of the RAS/MAPK pathway. In the present study, we characterized growth
      parameters, body composition, and nutritional aspects of children and adults (n =
      62) affected by these disorders, mainly Noonan syndrome, using an indirect method
      anthropometry-and a 24-hr recall questionnaire. The growth parameters in our
      cohort showed short stature, especially in individuals with RAF1 and SHOC2
      mutations, lower obesity rates compared to the control population, and BMI scores
      highest in individuals with BRAF mutations and lowest in individuals with SHOC2.
      Body composition showed a compromise in the upper arm muscle circumference, with
      a statistically significant difference in the z-score of triceps skinfold (P =
      0.0204) and upper arm fat area (P = 0.0388) between BRAF and SHOC2 groups and in
      the z-score of triceps skinfold between RAF1 and SHOC2 (P = 0.0218). The pattern
      of macronutrient consumption was similar to the control population. Our study is
      the first to address body composition in RASopathy individuals and the data
      indicate a compromise not only in adipose tissue, but also in muscle mass.
      Studies using different techniques, such as dual-energy X-ray absorptiometry or
      imaging studies, which give a more precise delineation of fat and non-fat mass,
      are required to confirm our results, ultimately causing an impact on management
      strategies. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038325
TI  - Element distribution and iron speciation in mature wheat grains (Triticum
      aestivum L.) using synchrotron X-ray fluorescence microscopy mapping and X-ray
      absorption near-edge structure (XANES) imaging.
AB  - Several studies have suggested that the majority of iron (Fe) and zinc (Zn) in
      wheat grains are associated with phytate, but a nuanced approach to unravel
      important tissue-level variation in element speciation within the grain is
      lacking. Here, we present spatially resolved Fe-speciation data obtained directly
      from different grain tissues using the newly developed synchrotron-based
      technique of X-ray absorption near-edge spectroscopy imaging, coupling this with
      high-definition MU-X-ray fluorescence microscopy to map the co-localization of
      essential elements. In the aleurone, phosphorus (P) is co-localized with Fe and
      Zn, and X-ray absorption near-edge structure imaging confirmed that Fe is
      chelated by phytate in this tissue layer. In the crease tissues, Zn is also
      positively related to P distribution, albeit less so than in the aleurone.
      Speciation analysis suggests that Fe is bound to nicotianamine rather than
      phytate in the nucellar projection, and that more complex Fe structures may also
      be present. In the embryo, high Zn concentrations are present in the root and
      shoot primordium, co-occurring with sulfur and presumably bound to thiol groups.
      Overall, Fe is mainly concentrated in the scutellum and co-localized with P. This
      high resolution imaging and speciation analysis reveals the complexity of the
      physiological processes responsible for element accumulation and
      bioaccessibility.

PMID- 27038326
TI  - Elevated plasma concentrations of bacterial ClpB protein in patients with eating
      disorders.
AB  - OBJECTIVE: Caseinolytic protease B (ClpB) produced by Enterobacteria, such as
      Escherichia coli, has been identified as a conformational mimetic of alpha
      melanocyte-stimulating hormone (alpha-MSH), an anorexigenic and anxiogenic
      neuropeptide. In mice, ClpB induces alpha-MSH cross-reactive antibodies and
      activates anorexigenic brain neurons. In patients with eating disorders (ED),
      anti-ClpB and anti-alpha-MSH antibodies correlate with psychopathological traits.
      However, it is not known if ClpB is present in human plasma including ED
      patients. METHODS: Plasma concentrations of ClpB were measured using a recently
      developed ClpB immunoassay in female patients with anorexia nervosa, bulimia
      nervosa, and binge-eating disorder and compared with healthy participants, all
      characterized by the Eating Disorder Inventory-2 (EDI-2) scale. RESULTS: We found
      that ClpB was readably detectable in plasma of healthy participants and ED
      patients and that its concentrations were elevated in ED patients, without
      significant differences in patient's subgroups. Plasma ClpB concentrations
      correlated with the EDI-2 scores, with alpha-MSH as well as with plasma levels of
      anti-ClpB and anti-alpha-MSH antibodies. DISCUSSION: These data revealed that
      bacterial ClpB is naturally present in human plasma and that its concentrations
      can be elevated in ED patients and associated with ED-related psychopathological
      traits. These results support a link between bacterial ClpB and the ED
      pathophysiology. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:805
      808).

PMID- 27038327
TI  - Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9.
AB  - Conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates is
      an important disease-associated posttranslational modification, although few
      inhibitors of this process are known. Herein, we report the discovery of an
      allosteric small-molecule binding site on Ubc9, the sole SUMO E2 enzyme. An X-ray
      crystallographic screen was used to identify two distinct small-molecule
      fragments that bind to Ubc9 at a site distal to its catalytic cysteine. These
      fragments and related compounds inhibit SUMO conjugation in biochemical assays
      with potencies of 1.9-5.8 mm. Mechanistic and biophysical analyses, coupled with
      molecular dynamics simulations, point toward ligand-induced rigidification of
      Ubc9 as a mechanism of inhibition.

PMID- 27038328
TI  - Effects of linker sequence modifications on the structure, stability, and
      biological activity of a cyclic alpha-conotoxin.
AB  - The cyclic conotoxin analogue cVc1.1 is a promising lead molecule for the
      development of new treatments for neuropathic and chronic pain. The design of
      this peptide includes a linker sequence that joins the N and C termini together,
      improving peptide stability while maintaining the structure and activity of the
      original linear Vc1.1. The effect of linker length on the structure, activity and
      stability of cyclised conotoxins has been studied previously but the effect of
      altering the composition of the linker sequence has not been investigated. In
      this study, we designed three analogues of cVc1.1 with linker sequences that
      varied in charge, hydrophobicity and hydrogen bonding capacity and examined the
      effect on structure, stability, membrane permeability and biological activity.
      The three designed peptides were successfully synthesized using solid phase
      peptide synthesis approaches and had similar structures and stability compared
      with cVc1.1. Despite modifications in charge, hydrophobicity and hydrogen bonding
      potential, which are all factors that can affect membrane permeability, no
      changes in the ability of the peptides to pass through membranes in either PAMPA
      or Caco-2 cell assay were observed. Surprisingly, modification of the linker
      sequence was deleterious to biological activity. These results suggest the linker
      sequence might be a useful part of the molecule for optimization of bioactivity
      and not just the physiochemical properties of cVc1.1. (c) 2016 Wiley Periodicals,
      Inc. Biopolymers (Pept Sci) 106: 864-875, 2016.

PMID- 27038329
TI  - Modifying the tumor microenvironment using nanoparticle therapeutics.
AB  - Treatment of cancer has come a long way from the initial 'radical surgeries' to
      the multimodality treatments. For the major part of the last century, cancer was
      considered as a monocellular disorder, and treatment strategies were designed
      according to that hypothesis. However, the mortality rate from cancer continued
      to be high and a comprehensive treatment remained elusive. Recent progress in
      research has demonstrated that tumors are a complex network of neoplastic and non
      neoplastic cells. The non-neoplastic cells, which are collectively called stroma,
      assist in tumor survival and progression. It has been shown that disrupting the
      tumor-stromal balance leads to significant effects on the tumor survival, and
      effective treatment can be achieved by targeting one or more of the stromal
      components. In this review, we summarize the roles of various stromal components
      in promoting tumor progression, and discuss innovative nanoparticle-mediated drug
      targeting strategies for stromal depletion and the subsequent effects on the
      tumors. Perspectives and the future directions are also provided. WIREs Nanomed
      Nanobiotechnol 2016, 8:891-908. doi: 10.1002/wnan.1406 For further resources
      related to this article, please visit the WIREs website.

PMID- 27038331
TI  - Developing consensus on hospital prescribing indicators of potential harm for
      infants and children.
AB  - AIMS: The aim of the study was to develop a list of hospital based paediatric
      prescribing indicators that can be used to assess the impact of electronic
      prescribing or clinical decision support tools on paediatric prescribing errors.
      METHODS: Two rounds of an electronic consensus method (eDelphi) were carried out
      with 21 expert panellists from the UK. Panellists were asked to score each
      prescribing indicator for its likelihood of occurrence and severity of outcome
      should the error occur. The scores were combined to produce a risk score and a
      median score for each indicator calculated. The degree of consensus between
      panellists was defined as the proportion that gave a risk score in the same
      category as the median. Indicators were included if a consensus of 80% or higher
      was achieved and were in the high risk categories. RESULTS: Each of the 21
      panellists completed an exploratory round and two rounds of scoring. This
      identified 41 paediatric prescribing indicators with a high risk rating and
      greater than 80% consensus. The most common error type within the indicators was
      wrong dose (n = 19) and the most common drug classes were antimicrobials (n = 10)
      and cardiovascular (n = 7). CONCLUSIONS: A set of 41 paediatric prescribing
      indicators describing potential harm for the hospital setting has been identified
      by an expert panel. The indicators provide a standardized method of evaluation of
      prescribing data on both paper and electronic systems. They can also be used to
      assess implementation of clinical decision support systems or other quality
      improvement initiatives.

PMID- 27038330
TI  - Electron microscopic localization of M2-muscarinic receptors in cholinergic and
      noncholinergic neurons of the laterodorsal tegmental and pedunculopontine nuclei
      of the rat mesopontine tegmentum.
AB  - Muscarinic m2 receptors (M2Rs) are implicated in autoregulatory control of
      cholinergic output neurons located within the pedunculopontine (PPT) and
      laterodorsal tegmental (LTD) nuclei of the mesopontine tegmentum (MPT). However,
      these nuclei contain many noncholinergic neurons in which activation of M2R
      heteroceptors may contribute significantly to the decisive role of the LTD and
      PPT in sleep-wakefulness. We examined the electron microscopic dual
      immunolabeling of M2Rs and the vesicular acetylcholine transporter (VAchT) in the
      MPT of rat brain to identify the potential sites for M2R activation. M2R
      immunogold labeling was predominately seen in somatodendritic profiles throughout
      the PPT/LTD complex. In somata, M2R immunogold particles were often associated
      with Golgi lamellae and cytoplasmic endomembrannes, but were rarely in contact
      with the plasma membrane, as was commonly seen in dendrites. Approximately 36% of
      the M2R-labeled somata and 16% of the more numerous M2R-labeled dendrites
      coexpressed VAchT. M2R and M2R/VAchT-labeled dendritic profiles received synapses
      from inhibitory- and excitatory-type axon terminals, over 88% of which were
      unlabeled and others contained exclusively M2R or VAchT immunoreactivity. In
      axonal profiles M2R immunogold was localized to plasmalemmal and cytoplasmic
      regions and showed a similar distribution in many VAchT-negative glial profiles.
      These results provide ultrastructural evidence suggestive of somatic endomembrane
      trafficking of M2Rs, whose activation serves to regulate the postsynaptic
      excitatory and inhibitory responses in dendrites of cholinergic and
      noncholinergic neurons in the MPT. They also suggest the possibility that M2Rs in
      this brain region mediate the effects of acetylcholine on the release of other
      neurotransmitters and on glial signaling. J. Comp. Neurol. 524:3084-3103, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27038332
TI  - Bioresorbable vascular scaffolds for small vessels coronary disease: The BVS-save
      registry.
AB  - OBJECTIVE: In this study, we investigated long-term results following
      bioresorbable vascular scaffold (BVS) implantation in small coronary arteries.
      BACKGROUND: Management of small coronary vessel disease with percutaneous
      coronary interventions (PCI) is often associated with high recurrencies and an
      increased risk of late or very late adverse events. Currently, little is known
      about BVS behavior in this setting. METHODS: A retrospective cohort analysis in a
      consecutive all-comer population was performed in patients that had a BVS
      implanted for coronary artery disease (CAD) in vessels with reference diameter
      <2.75 mm. Primary end-point was the occurrence of BVS failure (any event between
      target lesion revascularization (TLR) and definite/probable thrombosis) at the
      longest available follow-up. Secondary end-points were device-oriented clinical
      outcome (DOCE, a composite of cardiac death, target-vessel non-fatal myocardial
      infarction (MI) and TLR) and its single components at 12-month follow-up.
      RESULTS: A total of 121 patients (133 lesions) were treated between March 2013
      and December 2014 at three high volume Italian centers. From baseline clinical
      and angiographic characteristics emerges a highly complex patient population.
      Procedural success was obtained in 120 (99.2%) patients. In-hospital events
      included one cardiac death. At the longest available clinical follow-up (average
      12 +/- 6, median 11.4 months, interquartile ranges (IQR) 8, primary end-point
      occurred in 12 patients (9.0%), including 12 (9.0%) TLR and 2 (1.5%) BVS
      thrombosis. DOCE occurred in 9.0% of cases. The use of overlapping BVS in this
      setting did not increase the risk of adverse events. CONCLUSIONS: BVS
      implantation in a highly complex clinical and angiographic setting of small
      coronary vessels was technically feasible and effective in maintaining vessel
      patency after 12 months. (c) 2016 Wiley Periodicals, Inc.

PMID- 27038333
TI  - Insights into 6q21-q22: Refinement of the critical region for acro-cardio-facial
      syndrome.
AB  - Deletions on chromosome 6q are rarely reported in the literature, and genotype
      phenotype correlations are poorly understood. We report a child with a deletion
      of the 6q21-q22 chromosomal region, providing some intriguing results about the
      correlation between this region and acro-cardio-facial syndrome, congenital heart
      disease, split hand and foot malformation, and epilepsy.

PMID- 27038334
TI  - A novel chemically modified curcumin reduces inflammation-mediated connective
      tissue breakdown in a rat model of diabetes: periodontal and systemic effects.
AB  - BACKGROUND AND OBJECTIVE: Periodontal disease is the most common chronic
      inflammatory disease known to mankind (and the major cause of tooth loss in the
      adult population) and has also been linked to various systemic diseases,
      particularly diabetes mellitus. Based on the literature linking periodontal
      disease with diabetes in a "bidirectional manner", the objectives of the current
      study were to determine: (i) the effect of a model of periodontitis, complicated
      by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the
      response of the combination of this local and systemic phenotype to a novel
      pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin
      (CMC) 2.24. MATERIAL AND METHODS: Diabetes was induced in adult male rats by
      intravenous injection of streptozotocin (nondiabetic rats served as controls),
      and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into
      the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30
      mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of
      treatment, the rats were killed, and gingiva, jaws, tibia and skin were
      collected. The maxillary jaws and tibia were dissected and radiographed. The
      gingival tissues of each experimental group (n = 6 rats/group) were pooled,
      extracted, partially purified and, together with individual skin samples,
      analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography;
      MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western
      blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1beta,
      IL-6 and tumor necrosis factor-alpha], were measured in gingival tissue extracts
      and serum by ELISA. RESULTS: Systemic administration of CMC 2.24 to diabetic rats
      with endotoxin-induced periodontitis significantly inhibited alveolar bone loss
      and attenuated the severity of local and systemic inflammation. Moreover, this
      novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the
      pathologically excessive levels of inducible MMPs to near-normal levels, but
      appeared to have no significant effect on the constitutive MMPs required for
      physiologic connective tissue turnover. In addition to the beneficial effects on
      periodontal disease, induced both locally and systemically, CMC 2.24 also
      favorably affected extra-oral connective tissues, skin and skeletal bone.
      CONCLUSION: This study supports our hypothesis that CMC 2.24 is a potential
      therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular
      effects, which reduces local and systemic inflammation and prevents hyperglycemia
      and bacteria-induced connective tissue destruction.

PMID- 27038335
TI  - Risk of self-harm and nonfatal suicide attempts, and completed suicide in
      patients with psoriasis: a population-based cohort study.
AB  - BACKGROUND: Psoriasis is a common inflammatory skin disease, and inflammation may
      affect suicidal behaviour. Current data on the incidence and risk of suicidal
      behaviour in patients with psoriasis are scarce. OBJECTIVES: We investigated the
      association between psoriasis and the risk of self-harm and suicide attempts and
      suicides. METHODS: All Danish patients aged >= 18 years with mild or severe
      psoriasis (cases) from 1 January 1997 to 31 December 2011 were matched on age,
      sex and calendar time 1 : 5 with healthy controls. The outcome was a diagnosis of
      self-harm or a nonfatal suicide attempt, or completed suicide. Incidence rates
      per 10 000 person-years were calculated, and incidence rate ratios (IRRs) and
      confidence intervals (CIs) were estimated by Poisson regression models. RESULTS:
      The study cohort comprised 408 663 individuals, including 57 502 and 11 009
      patients with mild and severe psoriasis, respectively. In total 280 cases of self
      harm or suicide attempts, and 574 suicides occurred during follow-up. There was
      no increased risk of self-harm or suicide attempts in patients with mild
      psoriasis (IRR 1.01, 95% CI 0.17-2.01), but this risk was significantly increased
      in severe psoriasis (IRR 1.69, 95% CI 1.00-2.84). There was no increased risk of
      suicides in mild (IRR 1.05, 95% CI 0.84-1.32) or severe psoriasis (IRR 0.78, 95%
      CI 0.45-1.36). Similar results were found when suicides were confirmed by
      official forensic investigations, and when psoriasis was compared with atopic
      dermatitis. CONCLUSIONS: We found limited evidence to suggest an increased risk
      of self-harm and nonfatal suicide attempts in patients with psoriasis.
      Importantly, after adjustment for psoriatic arthritis this risk was no longer
      significantly increased. The risk of completed suicide was also not increased,
      regardless of psoriasis severity.

PMID- 27038336
TI  - p21-Activated kinase (Pak) regulates airway smooth muscle contraction by
      regulating paxillin complexes that mediate actin polymerization.
AB  - KEY POINTS: In airway smooth muscle, tension development caused by a contractile
      stimulus requires phosphorylation of the 20 kDa myosin light chain (MLC), which
      activates crossbridge cycling and the polymerization of a pool of submembraneous
      actin. The p21-activated kinases (Paks) can regulate the contractility of smooth
      muscle and non-muscle cells, and there is evidence that this occurs through the
      regulation of MLC phosphorylation. We show that Pak has no effect on MLC
      phosphorylation during the contraction of airway smooth muscle, and that it
      regulates contraction by mediating actin polymerization. We find that Pak
      phosphorylates the adhesion junction protein, paxillin, on Ser273, which promotes
      the formation of a signalling complex that activates the small GTPase, cdc42, and
      the actin polymerization catalyst, neuronal Wiskott-Aldrich syndrome protein (N
      WASP). These studies demonstrate a novel role for Pak in regulating the
      contractility of smooth muscle by regulating actin polymerization. ABSTRACT: The
      p21-activated kinases (Pak) can regulate contractility in smooth muscle and other
      cell and tissue types, but the mechanisms by which Paks regulate cell
      contractility are unclear. In airway smooth muscle, stimulus-induced contraction
      requires phosphorylation of the 20 kDa light chain of myosin, which activates
      crossbridge cycling, as well as the polymerization of a small pool of actin. The
      role of Pak in airway smooth muscle contraction was evaluated by inhibiting
      acetylcholine (ACh)-induced Pak activation through the expression of a kinase
      inactive mutant, Pak1 K299R, or by treating tissues with the Pak inhibitor, IPA3.
      Pak inhibition suppressed actin polymerization and contraction in response to
      ACh, but it did not affect myosin light chain phosphorylation. Pak activation
      induced paxillin phosphorylation on Ser273; the paxillin mutant, paxillin S273A,
      inhibited paxillin Ser273 phosphorylation and inhibited actin polymerization and
      contraction. Immunoprecipitation analysis of tissue extracts and proximity
      ligation assays in dissociated cells showed that Pak activation and paxillin
      Ser273 phosphorylation triggered the formation of an adhesion junction signalling
      complex with paxillin that included G-protein-coupled receptor kinase-interacting
      protein (GIT1) and the cdc42 guanine exchange factor, betaPIX (Pak interactive
      exchange factor). Assembly of the Pak-GIT1-betaPIX-paxillin complex was necessary
      for cdc42 and neuronal Wiskott-Aldrich syndrome protein (N-WASP) activation,
      actin polymerization and contraction in response to ACh. RhoA activation was also
      required for the recruitment of Pak to adhesion junctions, Pak activation,
      paxillin Ser273 phosphorylation and paxillin complex assembly. These studies
      demonstrate a novel role for Pak in the regulation of N-WASP activation, actin
      dynamics and cell contractility.

PMID- 27038338
TI  - Consumers' perception and acceptance of boiled and fermented sausages from
      strongly boar tainted meat.
AB  - Characteristic off-flavours may occur in uncastrated male pigs depending on the
      accumulation of androstenone and skatole. Feasible processing of strongly tainted
      carcasses is challenging but gains in importance due to the European ban on
      piglet castration in 2018. This paper investigates consumers' acceptability of
      two sausage types: (a) emulsion-type (BOILED) and (b) smoked raw-fermented
      (FERM). Liking (9 point scales) and flavour perception (check-all-that-apply with
      both, typical and negatively connoted sensory terms) were evaluated by 120
      consumers (within-subject design). Proportion of tainted boar meat (0, 50, 100%)
      affected overall liking of BOILED, F (2, 238)=23.22, P<.001, but not of FERM
      sausages, F (2, 238)=0.89, P=.414. Consumers described the flavour of BOILED-100
      as strong and sweaty. In conclusion, FERM products seem promising for processing
      of tainted carcasses whereas formulations must be optimized for BOILED in order
      to eliminate perceptible off-flavours. Boar taint rejection thresholds may be
      higher for processed than those suggested for unprocessed meat cuts. 

PMID- 27038340
TI  - Inter-Rater Agreement of Pressure Ulcer Risk and Prevention Measures in the
      National Database of Nursing Quality Indicators((r)) (NDNQI).
AB  - In this descriptive multi-site study, we examined inter-rater agreement on 11
      National Database of Nursing Quality Indicators((r)) (NDNQI((r)) ) pressure ulcer
      (PrU) risk and prevention measures. One hundred twenty raters at 36 hospitals
      captured data from 1,637 patient records. At each hospital, agreement between the
      most experienced rater and each other team rater was calculated for each measure.
      In the ratings studied, 528 patients were rated as "at risk" for PrU and,
      therefore, were included in calculations of agreement for the prevention
      measures. Prevalence-adjusted kappa (PAK) was used to interpret inter-rater
      agreement because prevalence of single responses was high. The PAK values for
      eight measures indicated "substantial" to "near perfect" agreement between most
      experienced and other team raters: Skin assessment on admission (.977, 95% CI
      [.966-.989]), PrU risk assessment on admission (.978, 95% CI [.964-.993]), Time
      since last risk assessment (.790, 95% CI [.729-.852]), Risk assessment method
      (.997, 95% CI [.991-1.0]), Risk status (.877, 95% CI [.838-.917]), Any prevention
      (.856, 95% CI [.76-.943]), Skin assessment (.956, 95% CI [.904-1.0]), and
      Pressure-redistribution surface use (.839, 95% CI [.763-.916]). For three
      intervention measures, PAK values fell below the recommended value of >=.610:
      Routine repositioning (.577, 95% CI [.494-.661]), Nutritional support (.500, 95%
      CI [.418-.581]), and Moisture management (.556, 95% CI [.469-.643]). Areas of
      disagreement were identified. Findings provide support for the reliability of 8
      of the 11 measures. Further clarification of data collection procedures is needed
      to improve reliability for the less reliable measures. (c) 2016 Wiley
      Periodicals, Inc. 

PMID- 27038339
TI  - Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent
      mechanism that is modulated by endocannabinoids.
AB  - The reinforcing effects of abused drugs are mediated by their ability to elevate
      nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to
      increase dopamine by an action potential-independent, non-exocytotic type of
      release called efflux, involving reversal of dopamine transporter function and
      driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also
      acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic
      voltammetry demonstrates that AMPH activates dopamine transients, reward-related
      phasic signals generated by burst firing of dopamine neurons and dependent on
      intact vesicular dopamine. Not established for AMPH but indicating a shared
      mechanism, endocannabinoids facilitate this activation of dopamine transients by
      broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled
      to pharmacological manipulations in awake rats, we investigated the action
      potential and endocannabinoid dependence of AMPH-induced elevations in nucleus
      accumbens dopamine. AMPH increased the frequency, amplitude and duration of
      transients, which were observed riding on top of slower dopamine increases.
      Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced
      dopamine elevations, identifying an action potential-dependent origin. Blocking
      cannabinoid type 1 receptors prevented AMPH from increasing transient frequency,
      similar to reported effects on other abused drugs, but not from increasing
      transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus
      accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and
      promoting the summation of temporally coincident transients, made more numerous,
      larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH
      eliciting action potential-independent dopamine efflux and vesicular dopamine
      depletion, and support endocannabinoids facilitating phasic dopamine signalling
      as a common action in drug reinforcement.

PMID- 27038341
TI  - Adolescents and social support situations.
AB  - The present study concerned adolescents' needs for social support with a focus on
      specific situations. The Adolescent Need for Social Support Questionnaire (ANSSQ)
      was developed based on qualitative interviews with typically developing
      adolescents about situations in which they need parent support. The questionnaire
      was tested on a sample of 380 Swedish 15-year-olds. A 3-component structure
      reflecting the dimensions "Home and school", "Low mood", and "Sex and alcohol"
      was tested in SEM analyses. Scales based on these dimensions, measuring support
      from parents and peers, yielded satisfactory psychometric results. Parent support
      was preferred over peer support for "Home and school" situations; in the other
      two areas peers were more likely to be the support providers. Females turned more
      often to parents and friends for support than males. Seeking parental support was
      positively related to adolescent disclosure and negatively related to adolescent
      secrecy, indicating convergent and discriminant validity. Further validation of
      the ANSSQ is discussed. The current study points to possibilities for adapting
      measures of social support to contexts. 

PMID- 27038342
TI  - Identification of inhibitors of the transmembrane protease FlaK of Methanococcus
      maripaludis.
AB  - GxGD-type intramembrane cleaving proteases (I-CLiPs) form a family of proteolytic
      enzymes that feature an aspartate-based catalytic mechanism. Yet, they
      structurally and functionally largely differ from the classical pepsin-like
      aspartic proteases. Among them are the archaeal enzyme FlaK, processing its
      substrate FlaB2 during the formation of flagella and gamma-secretase, which is
      centrally involved in the etiology of the neurodegenerative Alzheimer's disease.
      We developed an optimized activity assay for FlaK and based on screening of a
      small in-house library and chemical synthesis, we identified compound 9 as the
      first inhibitor of this enzyme. Our results show that this intramembrane protease
      differs from classical pepsin-like aspartic proteases and give insights into the
      substrate recognition of this enzyme. By providing the needed tools to further
      study the enzymatic cycle of FlaK, our results also enable further studies
      towards a functional understanding of other GxGD-type I-CLiPs.

PMID- 27038343
TI  - Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States
      of WNT-Induced Presomitic Mesoderm.
AB  - Presomitic mesoderm (PSM) cells are the precursors of the somites, which flank
      both sides of the neural tube and give rise to the musculo-skeletal system
      shaping the vertebrate body. WNT and FGF signaling control the formation of both
      the PSM and the somites and show a graded distribution with highest levels in the
      posterior PSM. We have used reporters for the mesoderm/PSM control genes T, Tbx6,
      and Msgn1 to investigate the differentiation of mouse ESCs from the naive state
      via EpiSCs to PSM cells. Here we show that the activation of WNT signaling by
      CHIR99021 (CH) in combination with FGF ligand induces embryo-like PSM at high
      efficiency. By varying the FGF ligand concentration, the state of PSM cells
      formed can be altered. High FGF concentration supports posterior PSM formation,
      whereas low FGF generates anterior/differentiating PSM, in line with in vivo
      data. Furthermore, the level of Msgn1 expression depends on the FGF ligand
      concentration. We also show that Activin/Nodal signaling inhibits CH-mediated PSM
      induction in EpiSCs, without affecting T-expression. Inversely, Activin/Nodal
      inhibition enhances PSM induction by WNT/high FGF signaling. The ability to
      generate PSM cells of either posterior or anterior PSM identity with high
      efficiency in vitro will promote the investigation of the gene regulatory
      networks controlling the formation of nascent PSM cells and their switch to
      differentiating/somitic paraxial mesoderm. Stem Cells 2016;34:1790-1800.

PMID- 27038344
TI  - 9th National Congress of the Italian Society for the Study of Eating Disorders
      (SISDCA) : Rome, 26-27 February 2016.

PMID- 27038345
TI  - Plasma orexin-A level associated with physical activity in obese people.
AB  - OBJECTIVE: To measure the amount of physical activity (PA) among obese adults,
      investigate the association between plasma orexin-A level and PA patterns, and
      explore the effect of orexin on the prevention and control of obesity. METHODS:
      Interviews were conducted in 218 participants (106 obese; 73 overweight; and 39
      normal) who ranged in age between 18 and 70 years using a survey that included
      sociodemographic variables. The International Physical Activity Questionnaire
      (IPAQ-long version) was used to measure PA. A total of 178 participants agreed to
      submit blood sample collections, and plasma orexin-A content was measured by
      ELISA testing. RESULTS: The average level of orexin-A was 85.34 +/- 42.85 ng/L in
      the obese group, 97.38 +/- 36.72 ng/L in the overweight group, and 106.56 +/-
      52.09 ng/L in the control group, which was significantly different (P = 0.03).
      The concentration of plasma orexin-A correlated with the total PA (P = 0.000),
      moderate PA (obese = 0.007; overweight: P = 0.000; control: P = 0.000), and
      walking PA (P = 0.000) in all three groups. Working and domestic PAs were
      significantly associated with the plasma orexin-A level (P < 0.0001).
      CONCLUSIONS: The plasma orexin-A level was associated with PA in obese and
      overweight people, including many aspects of daily life, such as working,
      domestic work, and walking especially.

PMID- 27038346
TI  - Errors in meta-analysis on prevalence of nonalcoholic fatty liver disease.

PMID- 27038347
TI  - Variance and variability, uncovering an underappreciated component of
      reproductive isolation.
AB  - Estimating the fitness of line crosses has been a key element in studies of
      inbreeding depression, hybridization, and speciation. Fitness values are
      typically compared using differences in the arithmetic mean of a fitness
      component between types of crosses. One aspect of fitness that is often
      overlooked is variance in offspring fitness over time. In the majority of
      studies, ignoring this aspect of fitness is unavoidable because it is impossible
      to estimate variance in offspring fitness over long time periods. Here, I
      describe a method of estimating variance in offspring fitness by substituting
      spatial variation for temporal variation and provide an empirical example. The
      method is based on Levene's test of homogeneity of variances. It is implemented
      by quantifying differences in residual variation among cross types. In a previous
      study, I performed crosses between populations of the annual plant Diodia teres
      and quantified hybrid fitness. In this study, another component of isolation and
      heterosis was revealed when considering variance in offspring fitness. When
      taking into account variance in offspring fitness using geometric mean fitness as
      the measure of performance, hybrids between populations from different habitats
      showed less heterosis than when calculating fitness based on arithmetic mean.
      This study demonstrates that variance in offspring fitness can be an important
      aspect of fitness that should be measured more frequently.

PMID- 27038348
TI  - Echocardiographic diagnosis of adult valvular heart disease.

PMID- 27038349
TI  - Age and gender differences in the influences of eNOS T-786C polymorphism on
      arteriosclerotic parameters in general population in Japan.
AB  - OBJECTIVE: The influence of T-786C polymorphism in the promoter region of
      endothelial nitric oxide synthase (eNOS) on arteriosclerotic parameters by age
      and gender were examined. METHODS: Brachial-ankle pulse wave velocity (baPWV),
      heart-rate adjusted augmentation index (AIx@75), pulse pressure (PP) and albumin
      creatinine ratio (ACR) were assessed as arteriosclerotic parameters in addition
      to non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (non-HDL-C/HDL
      C) ratio in 1499 participants. T-786C polymorphism (rs2070744) was screened using
      a TaqMan allelic discrimination assay. Analyses of covariance were carried.
      RESULTS: Women with the non-C allele showed significantly lower AIx@75 in
      participants aged <65 years and baPWV in participants aged >=65 years than those
      with C allele. In contrast, men with the non-C allele showed significantly higher
      PP in participants aged <65 years, and higher ACR and non-HDL-C/HDL-C ratio in
      participants aged >=65 years. In men on cholesterol-lowering medication, the non
      C allele carriers showed significantly higher non-HDL-C compared to those in the
      C allele carriers. CONCLUSIONS: eNOS T-786C polymorphism is significantly
      associated with arteriosclerotic parameters accompanied with age and gender
      differences, possibly involving antioxidative and/or endothelial signaling other
      than inflammatory signaling.

PMID- 27038350
TI  - Oestrogen receptors beta genotype in infertile Egyptian men with nonobstructive
      azoospermia.
AB  - In a prospective study, the polymorphism of oestrogen receptor beta gene was
      investigated in nonobstructive azoospermia patients. Ninety infertile patients
      with nonobstructive azoospermia diagnosed after two semen analysis, 2 weeks apart
      and negative testicular sperm extraction during intracytoplasmic sperm injection,
      and 60 fertile men as controls were enrolled in the study. Semen analysis,
      hormonal profile and allele-specific PCR reaction were performed to detect
      variants of the RsaI polymorphism of the oestrogen receptor beta gene for all
      patients and controls. The mean patient's age was significantly lower than the
      mean age of the controls (P < 0.05). There was a significant increase in the mean
      serum levels of FSH, LH, free testosterone and E2 and significant decrease in
      total testosterone in patients than controls (P < 0.05). In the patients, the
      frequency of the homozygous GG, heterozygous AG and homozygous AA genotype was
      83.3%, 14.3% and 3.3% respectively, whereas their frequencies in the controls
      were 95%, 5% and 0% respectively (odds ratio 3.8). There is no significant
      correlation between ERbeta polymorphisms and patient's age or pituitary and sex
      hormones (P > 0.05). Our findings suggested that in Egyptian population, genetic
      mutation in ERbeta is associated with the risk of nonobstructive azoospermia.

PMID- 27038351
TI  - A screening of medicinal compounds for their effect on egg strings and nauplii of
      the salmon louse Lepeophtheirus salmonis (Kroyer).
AB  - Egg strings and nauplii of the salmon louse Lepeophtheirus salmonis were exposed
      to a variety of medicinal compounds at 50 mg L(-1) for 30 min in two experiment
      series. This medicine concentration was selected as a starting point for a
      screening series. Hatching of egg strings and development to copepodid larvae
      were monitored in one experiment, and the survival and development of nauplii
      were monitored in the other. Two compounds, emamectin benzoate and cypermethrin,
      inhibited hatching effectively. Several compounds affected nauplii, either
      directly or through inhibiting development to the infective stage. A total of 50
      mg L(-1) of azamethiphos, cypermethrin, emamectin benzoate and propoxur was
      lethal to >70% of the larvae. Diflubenzuron, fenoxycarb, pymetrozine, pyriprole
      and tebufenozide diminished the ability of nauplii developing to copepodids. 

PMID- 27038352
TI  - The association of soy food consumption with the risk of subtype of breast
      cancers defined by hormone receptor and HER2 status.
AB  - Soy food intake has previously been associated with reduced breast cancer risk.
      Epidemiological evidence for subgroups of breast cancer, particularly by
      menopausal and hormone receptor status, is less consistent. To evaluate the role
      of hormone receptor and menopausal status on the association between soy food
      intake and breast cancer risk, we measured usual soy food intake in adolescence
      and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40
      70 years, recruited to the Shanghai Women's Health Study (1996-2000). After a
      median follow-up of 13.2 years (range: 0.01-15.0), 1,034 incident breast cancer
      cases were identified. Using Cox models, we found that adult soy intake was
      inversely associated with breast cancer risk [hazard ratio (HR) for fifth versus
      first quintile soy protein intake = 0.78; 95% confidence interval (CI):0.63
      0.97]. The association was predominantly seen in premenopausal women (HR = 0.46;
      95% CI:0.29-0.74). Analyses further stratified by hormone receptor status showed
      that adult soy intake was associated with significantly decreased risk of
      estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer in
      postmenopausal women (HR = 0.72; 95% CI:0.53-0.96) and decreased risk of ER-/PR-
      breast cancer in premenopausal women (HR = 0.46; 95% CI:0.22-0.97). The soy
      association did not vary by human epidermal growth factor-2 (HER2) status.
      Furthermore, we found that high soy intake during adulthood and adolescence was
      associated with reduced premenopausal breast cancer risk (HR = 0.53; 95% CI: 0.32
      0.88; comparing third vs. first tertile) while high adulthood soy intake was
      associated with postmenopausal breast cancer only when adolescent intake was low
      (HR = 0.63; 95% CI: 0.43-0.91). Our study suggests that hormonal status,
      menopausal status and time window of exposure are important factors influencing
      the soy-breast cancer association. 

PMID- 27038353
TI  - The IMI PROTECT project: purpose, organizational structure, and procedures.
AB  - The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European
      ConsorTium (PROTECT) initiative was a collaborative European project that sought
      to address limitations of current methods in the field of pharmacoepidemiology
      and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of
      the Innovative Medicines Initiative, a joint undertaking by the European Union
      and pharmaceutical industry. Thirty-five partners including academics,
      regulators, small and medium enterprises, and European Federation of
      Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two
      work packages within PROTECT implemented research examining the extent to which
      differences in the study design, methodology, and choice of data source can
      contribute to producing discrepant results from observational studies on drug
      safety. To evaluate the effect of these differences, the project applied
      different designs and analytic methodology for six drug-adverse event pairs
      across several electronic healthcare databases and registries. This papers
      introduces the organizational structure and procedures of PROTECT, including how
      drug-adverse event and data sources were selected, study design and analyses
      documents were developed, and results managed centrally.

PMID- 27038354
TI  - Risk of acute liver injury associated with use of antibiotics. Comparative cohort
      and nested case-control studies using two primary care databases in Europe.
AB  - PURPOSE: To assess the impact of varying study designs, exposure and outcome
      definitions on the risk of acute liver injury (ALI) associated with antibiotic
      use. METHODS: The source population comprised of patients registered in two
      primary care databases, in the UK and in Spain. We identified a cohort consisting
      of new users of antibiotics during the study period (2004-2009) and non-users
      during the study period or in the previous year. Cases with ALI were identified
      within this cohort and classified as definite or probable, based on recorded
      medical information. The relative risk (RR) of ALI associated with antibiotic use
      was computed using Poisson regression. For the nested case-control analyses, up
      to five controls were matched to each case by age, sex, date and practice (in
      CPRD) and odds ratios (OR) were computed with conditional logistic regression.
      RESULTS: The age, sex and year adjusted RRs of definite ALI in the current
      antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI:
      3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style,
      comorbidities and use of medications, the OR of ALI for current users of
      antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37)
      in BIFAP. CONCLUSION: Guided by a common protocol, both cohort and case-control
      study designs found an increased risk of ALI associated with the use of
      antibiotics in both databases, independent of the exposure and case definitions
      used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.

PMID- 27038355
TI  - Understanding inconsistency in the results from observational
      pharmacoepidemiological studies: the case of antidepressant use and risk of
      hip/femur fractures.
AB  - PURPOSE: Results from observational studies on the same exposure-outcome
      association may be inconsistent because of variations in methodological factors,
      clinical factors or health care systems. We evaluated the consistency of results
      assessing the association between antidepressant use and the risk of hip/femur
      fractures in three European primary care databases using two different study
      designs. METHODS: Cohort and nested case control studies were conducted in three
      European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to
      assess the association between use of antidepressants and hip/femur fracture. A
      common protocol and statistical analysis plan was applied to harmonize study
      design and conduct between data sources. RESULTS: Current use of antidepressants
      was consistently associated with a 1.5 to 2.5-fold increased risk of hip/femur
      fractures in all data sources with both designs, with estimates for SSRIs
      generally higher than those for TCAs. In general, risk estimates in Mondriaan,
      the smallest data source, were higher compared to the other data sources. This
      difference may be partially explained by an interaction between SSRI and age in
      Mondriaan. Adjustment for GP-recorded lifestyle factors and matching on general
      practice had negligible impact on adjusted relative risk estimates. CONCLUSION:
      We found a consistent increased risk of hip/femur fracture with current use of
      antidepressants across different databases and different designs. Applying
      similar pharmacoepidemiological study methods resulted in similar risks for TCA
      use and some variation for SSRI use. Some of these differences may express real
      (or natural) variance in the exposure-outcome co-occurrences.

PMID- 27038356
TI  - Case-only designs for studying the association of antidepressants and hip or
      femur fracture.
AB  - PURPOSE: The purpose of this study is to evaluate the performance and validity of
      the case-crossover (CCO) and self-controlled case-series (SCCS) designs when
      studying the association between hip/femur fracture (HF) and antidepressant (AD)
      use in general practitioner databases. In addition, comparability with cohort and
      case-control designs is discussed. METHODS: Adult patients with HF and who
      received an AD prescription during 2001-2009 were identified from UK's The Health
      Improvement Network (THIN) and the Dutch Mondriaan databases. AD exposure was
      classified into current, recent and past/non-use (reference). In the CCO, for
      each patient, a case moment (date of HF) and four prior control moments at -91, 
      182, -273 and -365 days were defined. In SCCS, incidence of HF was compared
      between exposure states. Conditional logistic regression was used in the CCO and
      Poisson regression in the SCCS to compute odds ratios and incidence rate ratios,
      respectively. In CCO, we adjusted for time-varying co-medication and in SCCS for
      age. RESULTS: Adjusted estimates for the effect of current AD exposure on HF were
      higher in the CCO (co-medication-adjusted odds ratio, THIN: 2.24, 95% confidence
      interval [CI]: 2.04-2.47; Mondriaan: 2.57, 95%CI [1.50, 4.43]) than in the SCCS
      (age-adjusted incidence rate ratio, THIN: 1.41, 95%CI [1.32, 1.49]; Mondriaan:
      2.14, 95%CI [1.51, 3.03]). The latter were comparable with the traditional
      designs. CONCLUSION: Case-only designs confirmed the association between AD and
      HF. The CCO design violated assumptions in this study with regard to
      exchangeability and length of exposure, and transient effects on outcome. The
      SCCS seems to be an appropriate design for assessing AD-HF association.

PMID- 27038357
TI  - Methodological comparison of marginal structural model, time-varying Cox
      regression, and propensity score methods: the example of antidepressant use and
      the risk of hip fracture.
AB  - BACKGROUND: Observational studies including time-varying treatments are prone to
      confounding. We compared time-varying Cox regression analysis, propensity score
      (PS) methods, and marginal structural models (MSMs) in a study of antidepressant
      [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip
      fracture. METHODS: A cohort of patients with a first prescription for
      antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch
      Mondriaan and Spanish Base de datos para la Investigacion Farmacoepidemiologica
      en Atencion Primaria (BIFAP) general practice databases for the period 2001-2009.
      The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was
      estimated using time-varying Cox regression, stratification and covariate
      adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse
      probability of censoring weights. RESULTS: The crude hazard ratio (HR) of SSRI
      use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan
      and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying
      Cox regression, stratification, and covariate adjustment using the PS, HRs
      increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63,
      4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39,
      1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded
      HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting
      for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP
      without accounting for censoring. CONCLUSIONS: In this empirical study,
      differences between the different methods to control for time-dependent
      confounding were small. The observed differences in treatment effect estimates
      between the databases are likely attributable to different confounding
      information in the datasets, illustrating that adequate information on (time
      varying) confounding is crucial to prevent bias.

PMID- 27038358
TI  - Instrumental variables analysis using multiple databases: an example of
      antidepressant use and risk of hip fracture.
AB  - PURPOSE: Instrumental variable (IV) analysis can control for unmeasured
      confounding, yet it has not been widely used in pharmacoepidemiology. We aimed to
      assess the performance of IV analysis using different IVs in multiple databases
      in a study of antidepressant use and hip fracture. METHODS: Information on adults
      with at least one prescription of a selective serotonin reuptake inhibitor (SSRI)
      or tricyclic antidepressant (TCA) during 2001-2009 was extracted from the THIN
      (UK), BIFAP (Spain), and Mondriaan (Netherlands) databases. IVs were created
      using the proportion of SSRI prescriptions per practice or using the one, five,
      or ten previous prescriptions by a physician. Data were analysed using
      conventional Cox regression and two-stage IV models. RESULTS: In the conventional
      analysis, SSRI (vs. TCA) was associated with an increased risk of hip fracture,
      which was consistently found across databases: the adjusted hazard ratio (HR) was
      approximately 1.35 for time-fixed and 1.50 to 2.49 for time-varying SSRI use,
      while the IV analysis based on the IVs that appeared to satisfy the IV
      assumptions showed conflicting results, e.g. the adjusted HRs ranged from 0.55 to
      2.75 for time-fixed exposure. IVs for time-varying exposure violated at least one
      IV assumption and were therefore invalid. CONCLUSIONS: This multiple database
      study shows that the performance of IV analysis varied across the databases for
      time-fixed and time-varying exposures and strongly depends on the definition of
      IVs. It remains challenging to obtain valid IVs in pharmacoepidemiological
      studies, particularly for time-varying exposure, and IV analysis should therefore
      be interpreted cautiously.

PMID- 27038359
TI  - Evaluating different physician's prescribing preference based instrumental
      variables in two primary care databases: a study of inhaled long-acting beta2
      agonist use and the risk of myocardial infarction.
AB  - PURPOSE: Instrumental variable (IV) analysis with physician's prescribing
      preference (PPP) as IV is increasingly used in pharmacoepidemiology. However, it
      is unclear whether this IV performs consistently across databases. We aimed to
      evaluate the validity of different PPPs in a study of inhaled long-acting beta2
      agonist (LABA) use and myocardial infarction (MI). METHODS: Information on adults
      with asthma and/or COPD and at least one prescription of beta2-agonist, or
      muscarinic antagonist was extracted from the CPRD (UK) and the Mondriaan
      (Netherlands) databases. LABA exposure was considered time-fixed or time-varying.
      We measured PPPs using previous LABA prescriptions of physicians or proportion of
      LABA prescriptions per practice. Correlation (r) and standardized difference
      (SDif) were used to assess assumption of IV analysis. RESULTS: For time-fixed
      LABA, the IV based on 10 previous prescriptions outperformed the other IVs
      regarding strength of the IV (r >= 0.15) and balance of confounders between IV
      categories (SDif < 0.10). None of the IVs we considered appeared to be valid for
      time-varying LABA. In CPRD (n = 490,499), which included approximately 18 times
      more subjects than Mondriaan (n = 27,459), IVs appeared more valid. LABA was not
      associated with MI; hazard ratios ranged from 0.86 to 1.18 for conventional
      analysis, and from 0.61 to 1.24 for the IV analyses with apparent valid IVs.
      CONCLUSIONS: The validity of physician's prescribing preference as IV strongly
      depends on how this IV is defined and in which database it is applied. Hence,
      general recommendations cannot be made, other than to generate several plausible
      IVs, assess their validity, and report the estimate(s) from apparently valid IVs.

PMID- 27038360
TI  - Impact of varying outcomes and definitions of suicidality on the associations of
      antiepileptic drugs and suicidality: comparisons from UK Clinical Practice
      Research Datalink (CPRD) and Danish national registries (DNR).
AB  - PURPOSE: The purpose of this study is to quantify the impact of the different
      outcomes and definitions of suicidality on the association between antiepileptic
      drugs (AEDs) and suicidality. METHODS: Retrospective cohort studies of selected
      AEDs (carbamazepine, gabapentin, lamotrigine, phenytoin, pregabalin, topiramate
      and valproate) using data from UK Clinical Practice Research Datalink (CPRD)
      alone and linked to UK Hospital Episode Statistics (HES) and UK Office of
      National Statistics (ONS), and from Danish national registries (DNR). Follow-up
      started at initiation of one of the study AEDs, divided into exposure periods, a
      maximum 90-day post-exposure period, and the reference period starting the day
      after the 90-day post-exposure period ended. Primary outcomes were completed
      suicide (SUI)/suicide attempt (SA) for CPRD and SUI/deliberate self-harm (DSH)
      for DNR. We applied adjusted Cox regression analyses and sensitivity analyses
      with varying outcome definitions. RESULTS: We analyzed 84,524 AED users from CPRD
      HES-ONS (1188 SUI/SA; 96 SUI) and 258,180 users from DNR (7561 SUI/DSH; 781 SUI).
      The adjusted hazard ratios (HRs) on SUI/SA ranged between 1.3 (95% confidence
      interval (CI): 0.84-2.00) for lamotrigine and 2.7 (1.24-5.81) for phenytoin in
      CPRD-HES-ONS, and between 0.9 (0.78-1.00) for valproate and 1.8 (1.10-3.07) for
      phenytoin on SUI/DSH in DNR. HRs for the primary outcomes varied consistently
      across exposure periods and data sources. HRs for SUI were in general lower, more
      stable and similar for periods of exposure and the 90-day post-exposure period.
      CONCLUSION: Applying different outcomes and definitions of suicidality had an
      impact on the relative risks of suicidality associated with the investigated AEDs
      with results for SUI being most consistent and reliable.

PMID- 27038361
TI  - Multi-centre, multi-database studies with common protocols: lessons learnt from
      the IMI PROTECT project.
AB  - PURPOSE: To assess the impact of a variety of methodological parameters on the
      association between six drug classes and five key adverse events in multiple
      databases. METHODS: The selection of Drug-Adverse Event pairs was based on public
      health impact, regulatory relevance, and the possibility to study a broad range
      of methodological issues. Common protocols and data analytical specifications
      were jointly developed and independently and blindly executed in different
      databases in Europe with replications in the same and different databases.
      RESULTS: The association between antibiotics and acute liver injury,
      benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long
      acting beta2-agonists and acute myocardial infarction was consistent in direction
      across multiple designs, databases and methods to control for confounding. Some
      variation in magnitude of the associations was observed depending on design,
      exposure and outcome definitions, but none of the differences were statistically
      significant. The association between anti-epileptics and suicidality was
      inconsistent across the UK CPRD, Danish National registries and the French PGRx
      system. Calcium channel blockers were not associated with the risk of cancer in
      the UK CPRD, and this was consistent across different classes of calcium channel
      blockers, cumulative durations of use up to >10 years and different types of
      cancer. CONCLUSIONS: A network for observational drug effect studies allowing the
      execution of common protocols in multiple databases was created. Increased
      consistency of findings across multiple designs and databases in different
      countries will increase confidence in findings from observational drug research
      and benefit/risk assessment of medicines.

PMID- 27038362
TI  - Plasma interleukin-10 predicts short-term mortality of acute-on-chronic hepatitis
      B liver failure.
AB  - BACKGROUND: Interleukin (IL)-10 is a pleiotropic cytokine with anti-inflammatory
      and immunosuppressive properties in liver failure. Biomarkers are urgently needed
      to predict prognosis of acute-on-chronic hepatitis B liver failure (ACHBLF). AIM:
      To investigate the potential diagnostic value of plasma IL-10 as a biomarker for
      predicting the mortality of ACHBLF. METHODS: This prospective study consisted of
      115 newly diagnosed ACHBLF patients from May 2009 to October 2013 as a training
      cohort and 54 ACHBLF patients from November 2013 to March 2015 as a validating
      cohort. Plasma IL-10 level was measured using enzyme-linked immunosorbent assay.
      RESULTS: In the training cohort, the plasma IL-10 level of nonsurvivals [median
      (centile25; centile75): 12.38 (8.76; 15.52) pg/mL] was significantly higher than
      that in survivals [6.55 (5.43; 7.65) pg/mL, P < 0.001]. Plasma IL-10 (hazard
      ratio = 1.205, 95% confidence interval: 1.145-1.267, P < 0.001) was identified as
      an independent risk factor for mortality of ACHBLF patients. Furthermore, plasma
      IL-10 showed higher area under the curve of receiver operating characteristic
      (AUROC) than model for end-stage liver diseases (MELD) for predicting 1-month
      (0.887 vs. 0.779, P < 0.05), 2-month (0.878 vs. 0.779, P < 0.05) and 3-month
      (0.917 vs. 0.776, P < 0.001) mortality. However, we did not find significant
      differences in AUROC between IL-10 and IL-10 plus MELD for 1-, 2- and 3-month
      mortality. ACHBLF patients with plasma IL-10 > 9.6 pg/mL showed poor survival
      time than patients with plasma IL-10 <= 9.6 pg/mL at the end of 1 month in the
      training and validation cohorts. CONCLUSIONS: Plasma IL-10 performed better than
      MELD in predicting the prognosis of acute-on-chronic hepatitis B liver failure.
      Furthermore, plasma IL-10 > 9.6 pg/mL predicts a poor 1-month mortality.

PMID- 27038363
TI  - Five-year experience with Ustekinumab for psoriasis: real-life data of a single
      centre.

PMID- 27038364
TI  - Dissolving Hydroxyolite: A DNA Molecule into Its Hydroxyapatite Mold.
AB  - In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that
      controls its dissolution in acidic environments remains unclear. Knowledge of
      such a process is highly desirable to provide better understanding of different
      pathologies, as for example osteoporosis, and of the HAp potential as vehicle for
      gene delivery to replace damaged DNA. In this work, the mechanism of dissolution
      in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has
      been investigated at the atomistic level using computer simulations. For this
      purpose, four consecutive (multi-step) molecular dynamics simulations, involving
      different temperatures and proton transfer processes, have been carried out.
      Results are consistent with a polynuclear decalcification mechanism in which
      proton transfer processes, from the surface to the internal regions of the
      particle, play a crucial role. In addition, the DNA remains protected by the
      mineral mold and transferred proton from both temperature and chemicals. These
      results, which indicate that biomineralization imparts very effective protection
      to DNA, also have important implications in other biomedical fields, as for
      example in the design of artificial bones or in the fight against osteoporosis by
      promoting the fixation of Ca(2+) ions. 

PMID- 27038365
TI  - Effect of Combined Action of Extracellular ATP and Elevated Calcium on Osteogenic
      Differentiation of Primary Cultures From Rat Calvaria.
AB  - The in vitro osteogenic differentiation has been intensively studied. However, it
      is not yet clear precisely how osteogenesis can be optimized. Changes in
      extracellular Ca(2+) concentration ([Ca(2+) ]e ), as well as modulation of
      purinergic receptors play an important role in the regulation of osteoblasts
      differentiation and bone formation. In this study, we investigated the effects of
      a combined treatment of ATPgamma-S and high [Ca(2+) ]e (5.35 mM) on osteogenic
      differentiation and function of primary cell cultures from rat calvaria. Our
      results indicate that ATPgamma-S stimulates cell transition from the G0 to S
      phase of cell cycle, involving the PI3K signaling pathway. Treatment with 10 or
      100 uM ATPgamma-S and [Ca(2+) ]e (ATP-[Ca(2+) ]e ) for 48 h increases cell number
      significantly above the control. ATPgamma-S treatment in osteogenic medium
      containing [Ca(2+) ]e stimulates the gene expression of BMP-4, BMP-5, and OPN at
      16, 48, and 72 h, respectively, above control. In same conditions, treatment for
      6 days with 10 uM UTP or 100 uM UDP significantly increased the ALP activity
      respect to control. Cells grown in osteogenic medium showed a statistically
      significant increase in calcium deposits at 15 and 18 days, for 10 uM ATPgamma-S
      treatment, and at 18 and 22 days, for [Ca(2+) ]e treatment, respect to control
      but ATP-[Ca(2+) ]e treatment shown a significant greater mineralization at 15
      days respect to ATPgamma-S, and at 18 days respect to both agonists. In
      conclusion, we demonstrated that an osteogenic medium containing 10 uM ATPgamma-S
      and 5.35 mM [Ca(2+) ]e enhance osteogenesis and mineralization by rat primary
      calvarial cells cultures. J. Cell. Biochem. 117: 2658-2668, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27038366
TI  - Differences in health-related quality of life between European and Asian patients
      with hepatocellular carcinoma.
AB  - AIM: The aim of this study is to explore the possible effects of clinical and
      cultural characteristics of hepatocellular carcinoma on patients' health-related
      quality of life (HRQoL). METHODS: Patients with hepatocellular carcinoma from
      Asian and European countries completed the EORTC QLQ-C30 and the EORTC QLQ-HCC18.
      Comparisons were made using Student's t-test and Wilcoxon rank-sum test with
      method of false discovery to correct multiple comparisons. Multiway analysis of
      variance and model selection were used to assess the effects of clinical
      characteristics and geographic areas. RESULTS: Two hundred and twenty-seven
      patients with hepatocellular carcinoma completed questionnaires. After adjusting
      for demographic and clinical characteristics, Asian patients still had
      significantly better HRQoL scores in emotional functioning, insomnia, (QLQ-C30)
      and in sexual interest (QLQ-HCC18). We also found an interaction in physical
      functioning (QLQ-C30) and fatigue (QLQ-HCC18) between geographic region and
      marital status, married European had worse HRQoL scores than Asian singles.
      CONCLUSIONS: Both clinical characteristics and geographic areas affected the
      HRQoL in with hepatocellular carcinoma. Cultural differences and clinical
      differences in the pattern of disease due to active surveillance of Asian
      countries may explain the results.

PMID- 27038367
TI  - Strongly Coupled Nafion Molecules and Ordered Porous CdS Networks for Enhanced
      Visible-Light Photoelectrochemical Hydrogen Evolution.
AB  - Strongly coupled Nafion molecules and ordered porous CdS networks are fabricated
      for visible-light photoelectrochemical (PEC) hydrogen evolution. The Nafion layer
      coating shifts the band position of CdS upward and accelerates charge transfer in
      the photoelectrode/electrolyte interface. It is highly expected that the strong
      coupling effect between organic and inorganic materials will provide new routes
      to advance PEC water splitting. 

PMID- 27038368
TI  - Astellifadiene: Structure Determination by NMR Spectroscopy and Crystalline
      Sponge Method, and Elucidation of its Biosynthesis.
AB  - Genome mining of a terpene synthase gene from Emericella variecolor NBRC 32302
      and its functional expression in Aspergillus oryzae led to the production of the
      new sesterterpene hydrocarbon, astellifadiene (1), having a 6-8-6-5-fused ring
      system. The structure of 1 was initially investigated by extensive NMR analyses,
      and was further confirmed by the crystalline sponge method, which established the
      absolute structure of 1 and demonstrated the usefulness of the method in the
      structure determination of complex hydrocarbon natural products. Furthermore, the
      biosynthesis of 1 was proposed on the basis of isotope-incorporation experiments
      performed both in vivo and in vitro. The cyclization of GFPP involves a
      protonation-initiated second cyclization sequence, 1,2-alkyl migration, and 1,5
      hydride shift to generate the novel scaffold of 1.

PMID- 27038369
TI  - Costs of hospital services in Jordan.
AB  - BACKGROUND: Policy makers are on quest for estimates of health costs to achieve
      maximum efficiency and sustainability. In Jordan, there is a scarcity of
      information on hospital service costs. AIM: The purpose of this study was to
      estimate the direct cost of hospital services in one of the biggest public
      hospitals in Amman, Jordan. METHODS: A retrospective analysis forms a 400-bed
      public urban hospital. Costs were estimated in Jordanian dinars (JD) (exchange
      rate was US$1.41). RESULTS: Inpatient costs contributed to 50% of all costs
      whilst outpatient clinics consumed 17%. Average cost per admission was JD 481.6
      (US$674.2), JD 106.7 (US$149.3) per inpatient day and JD 63.1 (US$88.3) per bed
      day. The average cost per visit to emergency room was JD 14.1 s (US$19.7). Cost
      per visit to ambulatory care services ranged between JD 37.3 and 473 (US$52.6
      662.2). The average cost per surgery was JD 322.1 (US$454.2). CONCLUSIONS: With
      high health costs, areas for improvements in efficiency and cost savings must be
      identified and discussed with managers and policy makers. A larger-scale study is
      advocated to understand the costs of various health providers such as military,
      teaching and private hospitals.

PMID- 27038370
TI  - Sensory innervation of the guinea pig colon and rectum compared using retrograde
      tracing and immunohistochemistry.
AB  - BACKGROUND: Neurons in lumbar and sacral dorsal root ganglia (DRG) comprise
      extrinsic sensory pathways to the distal colon and rectum, but their relative
      contributions are unclear. In this study, sensory innervation of the rectum and
      distal colon in the guinea pig was directly compared using retrograde labeling
      combined with immunohistochemistry. METHODS: The lipophilic tracer, DiI, was
      injected in either the rectum or distal colon of anesthetized guinea pigs, then
      DRG (T6 to S5) and nodose ganglia were harvested and labeled using antisera for
      calcitonin gene-related peptide (CGRP) and transient receptor potential vanilloid
      1(TRPV1). KEY RESULTS: More primary afferent cell bodies were labeled from the
      rectum than from the distal colon. Vagal sensory neurons, with cell bodies in the
      nodose ganglia comprised fewer than 0.5% of labeled sensory neurons. Spinal
      afferents to the distal colon were nearly all located in thoracolumbar DRG, in a
      skewed unimodal distribution (peak at L2); fewer than 1% were located in sacral
      ganglia. In contrast, spinal afferents retrogradely labeled from the rectum had a
      bimodal distribution, with one peak at L3 and another at S2. Fewer than half of
      all retrogradely labeled spinal afferent neurons were immunoreactive for CGRP or
      TRPV1 and these included the larger traced neurons, especially in thoracolumbar
      ganglia. CONCLUSIONS & INFERENCES: In the guinea pig, both the distal colon and
      the rectum receive a sensory innervation from thoracolumbar ganglia. Sacral
      afferents innervate the rectum but not the distal colon. Calcitonin gene-related
      peptide immunoreactivity was detectable in fewer than half of afferent neurons in
      both pathways.

PMID- 27038371
TI  - Role of Hemichannels in CNS Inflammation and the Inflammasome Pathway.
AB  - Neurodegenerative, cardiovascular, and metabolic disorders, once triggered, share
      a number of common features, including sustained inflammatory cell activation and
      vascular disruption. These shared pathways are induced independently of any
      genetic predisposition to the disease or the precise external stimulus. Glial
      cells respond to injury with an innate immune response that includes release of
      proinflammatory cytokines and chemokines. Vascular endothelial cells may also be
      affected, leading to opening of the blood-brain barrier that facilitates invasion
      by circulating inflammatory cells. Inflammation can trigger acute neural injury
      followed by chronic inflammation that plays a key role in neurodegenerative
      conditions. Gap junction channels normally allow direct cell-to-cell
      communication. They are formed by the docking of two hemichannels, one
      contributed by each of the neighboring cells. While the opening probability of
      these channels is tightly controlled under resting conditions, hemichannels can
      open in response to injury or inflammatory factors, forming a large, relatively
      nonselective membrane pore. In this review, we consider the CNS immune system
      from the perspective that modulating connexin hemichannel opening can prevent
      tissue damage arising from excessive and uncontrolled inflammation. We discuss
      connexin channel roles in microglia, astrocytes, and endothelial cells in both
      acute and chronic inflammatory conditions, and in particular describe the role of
      connexin hemichannels in the inflammasome pathway where they contribute to both
      its activation and its spread to neighboring cells. Finally, we describe the
      benefits of hemichannel block in animal models of brain injury.

PMID- 27038372
TI  - P2X7 Receptor as a Therapeutic Target.
AB  - P2X7 receptor is an ATP-gated cation channel that upon agonist interaction leads
      to cellular influx of Na(+) and Ca(2+) and efflux of K(+). P2X7 is expressed by a
      wide variety of cells and its activation mediates a large number of biological
      processes like inflammation, neuromodulation, cell death or cell proliferation
      and it has been associated to related pathological conditions including
      infectious, inflammatory, autoimmune, neurological, and musculoskeletal disorders
      and, in the last years, to cancer. This chapter describes structural features of
      P2X7, chemical properties of its agonist, antagonist, and allosteric modulators
      and summarizes recent advances on P2X7 receptor as therapeutic target in the
      aforementioned diseases. We also give an overview on recent literature suggesting
      that P2X7 single-nucleotide polymorphisms could be exploited as diagnostic
      biomarkers for the development of tailored therapies.

PMID- 27038373
TI  - Polymodal Transient Receptor Potential Vanilloid Type 1 Nocisensor: Structure,
      Modulators, and Therapeutic Applications.
AB  - Transient receptor potential (TRP) channels belong to a superfamily of sensory
      related ion channels responding to a wide variety of thermal, mechanical, or
      chemical stimuli. In an attempt to comprehend the piquancy and pain mechanism of
      the archetypal vanilloids, transient receptor potential vanilloid (TRPV) 1 was
      discovered. TRPV1, a well-established member of the TRP family, is implicated in
      a range of functions including inflammation, painful stimuli sensation, and
      mechanotransduction. TRPV1 channels are nonselective cation receptors that are
      gated by a broad array of noxious ligands. Such polymodal-sensor aspect makes the
      TRPV1 channel extremely versatile and important for its role in sensing burning
      pain. Besides ligands, TRPV1 signaling can also be modulated by lipids, secondary
      messengers, protein kinases, cytoskeleton, and several other proteins. Due to its
      central role in hyperalgesia transduction and inflammatory processes, it is
      considered as the primary pharmacological pain target. Moreover, understanding
      the structural and functional intricacies of the channel is indispensable for the
      therapeutic intervention of TRPV1 in pain and other pathological disorders. In
      this chapter, we seek to give a mechanistic outlook on the TRPV1 channel.
      Specifically, we will explore the TRPV1 structure, activation, modulation,
      ligands, and its therapeutic targeting. However, the major objective of this
      review is to highlight the fact that TRPV1 channel can be treated as an effective
      therapeutic target for treating several pain- and nonpain-related physiological
      and pathological states.

PMID- 27038374
TI  - TRPM8 Ion Channels as Potential Cancer Biomarker and Target in Pancreatic Cancer.
AB  - This article provides a review and discussion of the transient receptor potential
      melastatin-subfamily member 8 (TRPM8) ion channel as a potential biomarker and
      target in cancer. TRPM8 is a Ca(2+)-permeable channel that plays a major
      physiological role in cellular sensation and transduction of cold temperature.
      TRPM8 is aberrantly expressed in a variety of solid tumors including pancreatic
      cancer. In pancreatic adenocarcinoma cell lines and tissues, TRPM8 is
      overexpressed as compared to normal pancreatic ductal epithelia. Analysis of anti
      TRPM8 immunoreactivity in pancreatic adenocarcinoma indicates positive
      correlation of TRPM8 expression with tumor size and stages. The biological roles
      of TRPM8 in pancreatic cancer cells have been revealed from studies using RNA
      interference-mediated silencing of TRPM8. The experimental data show that TRPM8
      channels are required for sustaining proliferation and cell cycle progression,
      preventing replicative senescence, and promoting cell invasion. Evidence to date
      implicates a contributory role of TRPM8 channels in the pathogenesis of
      pancreatic neoplasms and other tumors. Research focus on the mechanisms that
      underlie TRPM8-mediated roles in tumor growth and metastasis may help establish a
      novel link of physicochemical changes with pancreatic carcinogenesis.
      Translational and clinical investigation to exploit TRPM8 as a molecular
      biomarker and therapeutic target is expected to make a positive impact on
      precision medicine in pancreatic cancer and other malignant diseases.

PMID- 27038375
TI  - Ion Channels in the Eye: Involvement in Ocular Pathologies.
AB  - The eye is the sensory organ of vision. There, the retina transforms photons into
      electrical signals that are sent to higher brain areas to produce visual
      sensations. In the light path to the retina, different types of cells and tissues
      are involved in maintaining the transparency of avascular structures like the
      cornea or lens, while others, like the retinal pigment epithelium, have a
      critical role in the maintenance of photoreceptor function by regenerating the
      visual pigment. Here, we have reviewed the roles of different ion channels
      expressed in ocular tissues (cornea, conjunctiva and neurons innervating the
      ocular surface, lens, retina, retinal pigment epithelium, and the inflow and
      outflow systems of the aqueous humor) that are involved in ocular disease
      pathophysiologies and those whose deletion or pharmacological modulation leads to
      specific diseases of the eye. These include pathologies such as retinitis
      pigmentosa, macular degeneration, achromatopsia, glaucoma, cataracts, dry eye, or
      keratoconjunctivitis among others. Several disease-associated ion channels are
      potential targets for pharmacological intervention or other therapeutic
      approaches, thus highlighting the importance of these channels in ocular
      physiology and pathophysiology.

PMID- 27038376
TI  - Calcium-Activated Potassium Channels: Potential Target for Cardiovascular
      Diseases.
AB  - Ca(2+)-activated K(+) channels (KCa) are classified into three subtypes: big
      conductance (BKCa), intermediate conductance (IKCa), and small conductance (SKCa)
      KCa channels. The three types of KCa channels have distinct physiological or
      pathological functions in cardiovascular system. BKCa channels are mainly
      expressed in vascular smooth muscle cells (VSMCs) and inner mitochondrial
      membrane of cardiomyocytes, activation of BKCa channels in these locations
      results in vasodilation and cardioprotection against cardiac ischemia. IKCa
      channels are expressed in VSMCs, endothelial cells, and cardiac fibroblasts and
      involved in vascular smooth muscle proliferation, migration, vessel dilation, and
      cardiac fibrosis. SKCa channels are widely expressed in nervous and
      cardiovascular system, and activation of SKCa channels mainly contributes
      membrane hyperpolarization. In this chapter, we summarize the physiological and
      pathological roles of the three types of KCa channels in cardiovascular system
      and put forward the possibility of KCa channels as potential target for
      cardiovascular diseases.

PMID- 27038377
TI  - The Modulation of Potassium Channels in the Smooth Muscle as a Therapeutic
      Strategy for Disorders of the Gastrointestinal Tract.
AB  - Alterations of smooth muscle contractility contribute to the pathophysiology of
      important functional gastrointestinal disorders (FGIDs) such as functional
      dyspepsia and irritable bowel syndrome. Consequently, drugs that decrease smooth
      muscle contractility are effective treatments for these diseases. Smooth muscle
      contraction is mainly triggered by Ca(2+) influx through voltage-dependent
      channels located in the plasma membrane. Thus, the modulation of the membrane
      potential results in the regulation of Ca(2+) influx and cytosolic levels. K(+)
      channels play fundamental roles in these processes. The open probability of K(+)
      channels increases in response to various stimuli, including membrane
      depolarization (voltage-gated K(+) [K(V)] channels) and the increase in cytosolic
      Ca(2+) levels (Ca(2+)-dependent K(+) [K(Ca)] channels). K(+) channel activation
      is mostly associated with outward K(+) currents that hyperpolarize the membrane
      and reduce cell excitability and contractility. In addition, some K(+) channels
      are open at the resting membrane potential values of the smooth muscle cells in
      some gut segments and contribute to set the resting membrane potential itself.
      The closure of these channels induces membrane depolarization and smooth muscle
      contraction. K(V)1.2, 1.5, 2.2, 4.3, 7.4 and 11.1, K(Ca)1.1 and 2.3, and inwardly
      rectifying type 6K(+) (K(ir)6) channels play the most important functional roles
      in the gastrointestinal smooth muscle. Activators of all these channels may
      theoretically relax the gastrointestinal smooth muscle and could therefore be
      promising new therapeutic options for FGID. The challenge of future drug research
      and development in this area will be to synthesize molecules selective for the
      channel assemblies expressed in the gastrointestinal smooth muscle.

PMID- 27038378
TI  - Targeting the Channel Activity of Viroporins.
AB  - Since the discovery that certain small viral membrane proteins, collectively
      termed as viroporins, can permeabilize host cellular membranes and also behave as
      ion channels, attempts have been made to link this feature to specific biological
      roles. In parallel, most viroporins identified so far are virulence factors, and
      interest has focused toward the discovery of channel inhibitors that would have a
      therapeutic effect, or be used as research tools to understand the biological
      roles of viroporin ion channel activity. However, this paradigm is being shifted
      by the difficulties inherent to small viral membrane proteins, and by the
      realization that protein-protein interactions and other diverse roles in the
      virus life cycle may represent an equal, if not, more important target.
      Therefore, although targeting the channel activity of viroporins can probably be
      therapeutically useful in some cases, the focus may shift to their other
      functions in following years. Small-molecule inhibitors have been mostly
      developed against the influenza A M2 (IAV M2 or AM2). This is not surprising
      since AM2 is the best characterized viroporin to date, with a well-established
      biological role in viral pathogenesis combined the most extensive structural
      investigations conducted, and has emerged as a validated drug target. For other
      viroporins, these studies are still mostly in their infancy, and together with
      those for AM2, are the subject of the present review.

PMID- 27038379
TI  - Contribution of Automated Technologies to Ion Channel Drug Discovery.
AB  - Automated technologies are now resolving the historical relegation that ion
      channels have endured as targets for the new drug discovery and development
      global efforts. The richness and adequacy of functional assay methodologies,
      remarkably fluorescence-based detection of ions fluxes and patch-clamp
      electrophysiology recording of ionic currents, are now automated and increasingly
      employed for the analysis of ion channel activity. While the former is currently
      the most commonly applied, the latter is finally reaching the throughput capacity
      to be engaged in the primary screening of chemical libraries conformed by
      hundreds of thousands of compounds. The use of automated instrumentation for the
      study of ion channel functionality (and dysfunctionality), particularly in the
      search for novel pharmacological agents with therapeutic purposes, has now
      reached out beyond the industrial setting, its original natural enclave, and is
      making its way into a growing number of academic labs and core facilities. The
      present chapter reviews the increasing contributions accomplished by a variety of
      different key automated technologies which have revolutionized the strategies to
      approach the discovery and development of new drugs targeting ion channels.

PMID- 27038380
TI  - Preface.

PMID- 27038381
TI  - Reproductive isolation and introgression between sympatric Mimulus species.
AB  - Incompletely isolated species provide an opportunity to investigate the genetic
      mechanisms and evolutionary forces that maintain distinct species in the face of
      ongoing gene flow. Here, we use field surveys and reduced representation
      sequencing to characterize the patterns of reproductive isolation, admixture and
      genomic divergence between populations of the outcrossing wildflower Mimulus
      guttatus and selfing M. nasutus. Focusing on a single site where these two
      species have come into secondary contact, we find that phenological isolation is
      strong, although incomplete, and is likely driven by divergence in response to
      photoperiod. In contrast to previous field studies, which have suggested that F1 
      hybrid formation might be rare, we discover patterns of genomic variation
      consistent with ongoing introgression. Strikingly, admixed individuals vary
      continuously from highly admixed to nearly pure M. guttatus, demonstrating
      ongoing hybridization and asymmetric introgression from M. nasutus into M.
      guttatus. Patterns of admixture and divergence across the genome show that levels
      of introgression are more variable than expected by chance. Some genomic regions
      show a reduced introgression, including one region that overlaps a critical
      photoperiod QTL, whereas other regions show elevated levels of interspecific gene
      flow. In addition, we observe a genome-wide negative relationship between
      absolute divergence and the local recombination rate, potentially indicating
      natural selection against M. nasutus ancestry in M. guttatus genetic backgrounds.
      Together, our results suggest that Mimulus speciation is both ongoing and dynamic
      and that a combination of divergence in phenology and mating system, as well as
      selection against interspecific alleles, likely maintains these sympatric
      species.

PMID- 27038382
TI  - Impacts of ferrate oxidation on natural organic matter and disinfection byproduct
      precursors.
AB  - This study investigated the effectiveness of ferrate (Fe(VI)) oxidation in
      combination with ferric chloride coagulation on the removal of natural organic
      matter (NOM) and disinfection byproduct (DBP) precursors. Twelve natural waters
      were collected and four treatment scenarios were tested at bench-scale. Results
      showed that intermediate-ferrate treatment (i.e., coagulation and particle
      removal followed by ferrate oxidation) was most effective followed by pre-ferrate
      treatment (i.e., ferrate oxidation followed by coagulation and particle removal
      (conventional treatment)) or conventional treatment alone (i.e., no oxidation),
      and the least effective was ferrate oxidation alone (i.e., no coagulation). At
      typical doses, direct ferrate oxidation of raw water decreased DBP formation
      potentials (DBPFPs) by about 30% for trihalomethanes (THMs), 40% for
      trihaloacetic acids (THAAs), 10% for dihaloacetic acids (DHAAs), 30% for
      dihaloacetonitriles (DHANs), and 5% for haloketones (HKs). The formation
      potential of chloropicrin (CP) consistently increased after direct ferrate
      oxidation. Pre-ferrate followed by conventional treatment was similar to
      conventional treatment alone for NOM and DBP precursor removal. Ferrate pre
      oxidation had positive effects on subsequent coagulation/particle removal for THM
      and THAA precursor removal and may allow the use of lower coagulant doses due to
      the Fe(III) introduced by ferrate decomposition. On the other hand, intermediate
      ferrate resulted in substantially improved removal of NOM and DBP precursors,
      which can be attributed to initial removal by coagulation and particle removal,
      leaving precursors that are particularly susceptible to oxidation by ferrate. The
      Fe(III) resulting from ferrate decay during intermediate-ferrate process was
      primarily present as particulate iron and could be effectively removed by
      filtration.

PMID- 27038383
TI  - Evaluation of chain architectures and charge properties of various starch-based
      flocculants for flocculation of humic acid from water.
AB  - Three different starch-based flocculants with various chain architectures and
      charge properties have been prepared through etherification, graft
      copolymerization, or their combination. Two of the flocculants (starch-graft
      poly[(2-methacryloyloxyethyl) trimethyl ammonium chloride] and starch-3-chloro-2
      hydroxypropyl triethyl ammonium chloride, denoted as STC-g-PDMC and STC-CTA
      respectively) are cationic, and another one (carboxymethyl starch-graft-poly[(2
      methacryloyloxyethyl) trimethyl ammonium chloride], denoted as CMS-g-PDMC) is
      amphoteric. Those three flocculants have shown far different flocculation
      efficiency and floc properties for the removal of humic acid (HA) from water due
      to their distinct structural features. The effects of pH, flocculant dose, and
      initial HA concentration have been studied systematically. Accordingly, STC-g
      PDMC and CMS-g-PDMC with strongly cationic branch chains have much better
      flocculation performance than polyaluminum chloride (PAC) and STC-CTA, the latter
      of which features linear chain architecture and strongly cationic pieces lying on
      its chain backbone. It indicates that the architecture of cationic branch chains
      plays an important role in HA flocculation due to their significantly enhanced
      bridging effects. Moreover, STC-g-PDMC has higher HA removal efficiency and
      better floc properties than CMS-g-PDMC, suggesting that charge neutralization
      effects make notable contributions to HA removal and that the additional anionic
      pieces on CMS-g-PDMC can weaken its flocculation performance. In addition, STC-g
      PDMC used as coagulant aid for PAC has also been tried, which observably reduces
      the optimal dose of the inorganic coagulant.

PMID- 27038384
TI  - Influence of the large-small split effect on strategy choice in complex
      subtraction.
AB  - Two main theories have been used to explain the arithmetic split effect: decision
      making process theory and strategy choice theory. Using the inequality paradigm,
      previous studies have confirmed that individuals tend to adopt a plausibility
      checking strategy and a whole-calculation strategy to solve large and small split
      problems in complex addition arithmetic, respectively. This supports strategy
      choice theory, but it is unknown whether this theory also explains performance in
      solving different split problems in complex subtraction arithmetic. This study
      used small, intermediate and large split sizes, with each split condition being
      further divided into problems requiring and not requiring borrowing. The reaction
      times (RTs) for large and intermediate splits were significantly shorter than
      those for small splits, while accuracy was significantly higher for large and
      middle splits than for small splits, reflecting no speed-accuracy trade-off.
      Further, RTs and accuracy differed significantly between the borrow and no-borrow
      conditions only for small splits. This study indicates that strategy choice
      theory is suitable to explain the split effect in complex subtraction arithmetic.
      That is, individuals tend to choose the plausibility-checking strategy or the
      whole-calculation strategy according to the split size.

PMID- 27038385
TI  - Plenary reviews of the 28th Fungal Genetics Conference.

PMID- 27038386
TI  - Immunoblotting and Immunodetection.
AB  - Immunoblotting (western blotting) is used to identify specific antigens
      recognized by polyclonal or monoclonal antibodies. This unit provides protocols
      for all steps, starting with solubilization of the protein samples, usually by
      means of SDS and reducing agents. Following solubilization, the material is
      separated by SDS-PAGE and the antigens are electrophoretically transferred to a
      membrane, a process that can be monitored by reversible staining with Ponceau S.
      The transferred proteins are bound to the surface of the membrane, providing
      access to immunodetection reagents. After nonspecific binding sites are blocked,
      the membrane is probed with the primary antibody and washed. The antibody-antigen
      complexes are tagged with fluorophores, horseradish peroxidase, or alkaline
      phosphatase coupled to a secondary anti-IgG antibody, and detected using
      appropriate fluorescent imaging technologies or with chromogenic or luminescent
      substrates. Finally, membranes may be stripped and reprobed.

PMID- 27038387
TI  - Analysis of Individual Signaling Complexes by mMAPS, a Flow-Proteometric System.
AB  - Signal transduction is essential for maintaining normal cell physiological
      functions, and deregulation of signaling can lead to diseases such as diabetes
      and cancers. Some of the major players in signal delivery are molecular complexes
      composed of proteins and nucleic acids. This unit describes a technique called
      microchannel for multiparameter analysis of proteins in a single complex (mMAPS)
      for analyzing and quantifying individual target signaling complexes. mMAPS is a
      flow-proteometric system that allows detection of individual proteins or
      complexes flowing through a microfluidic channel. Specific target proteins and
      nucleic acids labeled by fluorescent tags are harvested from tissues or cultured
      cells for analysis by the mMAPS system. Overall, mMAPS enables both detection of
      multiple components within a single complex and direct quantification of
      different populations of molecular complexes in one setting in a short timeframe
      and requiring very low sample input.

PMID- 27038388
TI  - Molecular Dissection of Chromatin Maturation via Click Chemistry.
AB  - DNA synthesis and chromatin assembly are the two most critical processes of
      eukaryotic cell division. It is well known that their coordination is tightly
      regulated. Although the interplay between DNA and its higher-order chromatin
      state is integral for many processes, including cell survival and genome
      stability, little is known about the re-establishment of chromatin structure
      during the cell cycle. Moreover, the extent to which the fidelity of the newly
      synthesized chromatin plays a role in the maintenance of cellular identity is
      still under debate. Here, we present a novel approach to purify nascent chromatin
      from the replication fork. In this protocol, we take advantage of click
      chemistry, a method that allows efficient conjugation of azide-containing biotin
      molecules to ethynyl-labeled nucleic acids. Using this approach, we selectively
      enrich biotin-nucleic acid conjugates via streptavidin affinity purification to
      pull down and assess chromatin states as well as chromatin-bound complexes from
      newly replicated DNA fragments.

PMID- 27038389
TI  - Metabolomics by Gas Chromatography-Mass Spectrometry: Combined Targeted and
      Untargeted Profiling.
AB  - Gas chromatography-mass spectrometry (GC-MS)-based metabolomics is ideal for
      identifying and quantitating small-molecule metabolites (<650 Da), including
      small acids, alcohols, hydroxyl acids, amino acids, sugars, fatty acids, sterols,
      catecholamines, drugs, and toxins, often using chemical derivatization to make
      these compounds sufficiently volatile for gas chromatography. This unit shows how
      GC-MS-based metabolomics allows integration of targeted assays for absolute
      quantification of specific metabolites with untargeted metabolomics to discover
      novel compounds. Complemented by database annotations using large spectral
      libraries and validated standard operating procedures, GC-MS can identify and
      semiquantify over 200 compounds from human body fluids (e.g., plasma, urine, or
      stool) per study. Deconvolution software enables detection of more than 300
      additional unidentified signals that can be annotated through accurate mass
      instruments with appropriate data processing workflows, similar to untargeted
      profiling using liquid chromatography-mass spectrometry. GC-MS is a mature
      technology that uses not only classic detectors (quadrupole) but also target mass
      spectrometers (triple quadrupole) and accurate mass instruments (quadrupole-time
      of flight). This unit covers sample preparation from mammalian samples, data
      acquisition, quality control, and data processing.

PMID- 27038390
TI  - Construction of a Sequencing Library from Circulating Cell-Free DNA.
AB  - Circulating DNA is cell-free DNA (cfDNA) in serum or plasma that can be used for
      non-invasive prenatal testing, as well as cancer diagnosis, prognosis, and
      stratification. High-throughput sequence analysis of the cfDNA with next
      generation sequencing technologies has proven to be a highly sensitive and
      specific method in detecting and characterizing mutations in cancer and other
      diseases, as well as aneuploidy during pregnancy. This unit describes detailed
      procedures to extract circulating cfDNA from human serum and plasma and generate
      sequencing libraries from a wide concentration range of circulating DNA.

PMID- 27038392
TI  - Risk and outcomes of methicillin-resistant Staphylococcus aureus (MRSA)
      bacteremia among patients admitted with and without MRSA nares colonization.
AB  - BACKGROUND: The risk of nosocomial methicillin-sensitive Staphylococcus aureus
      bacteremia in patients with nasal colonization on admission is 3-fold higher than
      in patients who are not colonized. Limited data on this question have been
      reported for methicillin-resistant S aureus (MRSA). METHODS: This is an
      observational cohort study of patients admitted to a tertiary care medical center
      from October 1, 2007-September 30, 2013, who underwent active screening for nasal
      colonization with MRSA. RESULTS: There were 29,371 patients who underwent
      screening for nasal MRSA colonization; 3,262 (11%) were colonized with MRSA.
      There were 32 cases of MRSA bacteremia among colonized patients, for an incidence
      of 1%. Thirteen cases of bacteremia occurred in non-MRSA-colonized patients, for
      an incidence of 0.05%. The odds of developing MRSA bacteremia for patients who
      were nasally colonized with MRSA compared with those who were not colonized were
      19.89. There was no difference between colonized and noncolonized subjects with
      bacteremia in all-cause mortality at 30 days or 1 year. CONCLUSIONS: In a setting
      with active screening for MRSA, the risk of MRSA bacteremia is 19.89-fold higher
      among colonized than noncolonized patients.

PMID- 27038393
TI  - Prediction of surgical site infection after colorectal surgery.
AB  - BACKGROUND: Surgical site infection (SSI) after colorectal surgery is a frequent
      complication associated with substantial morbidity. Our objective was to identify
      surgical predictors of SSI in patients undergoing colorectal surgery using a
      retrospective case-control design. MATERIAL AND METHODS: Randomly selected
      patients from all those undergoing colorectal surgery (2007-2013). Cases were
      patients who developed SSI within 30 days. Controls were patients who did not
      develop SSI within 30 days. Patients undergoing multiple procedures during a
      single surgical intervention were excluded. SSI was diagnosed according to
      Centers for Disease Control and Prevention definitions. The main outcome measures
      were SSI, surgical variables, and cumulative survival (Kaplan-Meier method).
      Variables considered predictors were compared using log-rank test. RESULTS: Of
      911 patients undergoing colorectal surgery, 221 developed SSI (24.3%; 95%
      confidence interval, 24.0-24.6). On univariate analysis, significant risk factors
      for SSI were: female sex (P = .02), >72 hours preoperative stay (P = .04), open
      surgery (P = .08), incision class: contaminated and dirty (P = .001), and
      emergency procedures (P = .006). On multivariate analysis, significant
      independent predictors of SSI and survival were dirty surgery (hazard ratio [HR],
      2.12; P = .015), contaminated surgery (HR, 1.74; P = .009), female sex (HR, 1.58;
      P = .003), open surgery, (HR, 1.51; P = .015) and >72 hours preoperative stay
      (HR, 1.48; P = .024). CONCLUSIONS: Dirty or contaminated surgery, female sex,
      open surgery, and >72 hours preoperative stay were significant predictors of SSI.

PMID- 27038394
TI  - Crisis prevention and management by infection control nurses during the Middle
      East respiratory coronavirus outbreak in Korea.
AB  - A Middle East respiratory coronavirus (MERS-CoV) outbreak occurred in Korea
      between June 20 and July 28, 2015. A total of 186 patients were confirmed as
      being infected with MERS-CoV, 36 of whom died. Infection control nurses referred
      to hospital guidelines to address the screening and isolation needs of patients
      and instigated a variety of infection control activities to prevent MERS-CoV
      transmission at the frontlines of patient care. Their concerted effort is
      believed to have been instrumental in ending the outbreak. 

PMID- 27038395
TI  - Feasibility of Pegylated Interferon in Children and Young Adults With Resected
      High-Risk Melanoma.
AB  - BACKGROUND: Pegylated interferon alpha-2b (IFN alpha-2b) improves disease-free
      survival in adults with resected stage III melanoma. We conducted a study to
      determine the feasibility and safety of incorporating pegylated IFN alpha-2b as
      adjuvant therapy in the treatment of children and adolescents with high-risk
      melanoma. Pharmacokinetic studies of IFN alpha-2b and neuropsychological and
      quality of life (OL) assessments were performed. PATIENT AND METHODS: Eligible
      patients with resected American Joint Committee on Cancer Stage IIC, IIIA, and
      IIIB cutaneous melanoma received nonpegylated IFN alpha-2b 20 million units/m(2)
      /day intravenously 5 days per week for 4 weeks (induction) followed by pegylated
      IFN alpha-2b 1 MUg/kg/dose weekly subcutaneously (SQ) for 48 weeks (maintenance).
      RESULTS: Twenty-three patients (15 females, median age 10 years) were enrolled.
      All patients completed induction therapy; five patients did not complete
      maintenance therapy either because of recurrent disease (n = 2) or toxicity (n =
      3). The most common grade 3 and 4 toxicities of pegylated IFN alpha-2b were
      neutropenia (35%) and elevated liver transaminases (17%). The median nonpegylated
      IFN alpha-2b AUC0-infinity (5,026 pcg?hr/ml) was similar to adults. The median
      pegylated IFN alpha-2b exposure (48,480 pcg?hr/ml) was greater than the
      cumulative weekly exposure for nonpegylated IFN alpha-2b administered SQ three
      times per week (TIW). Validated measures demonstrated an improvement in QOL
      scores and no decline in psychological functioning over the course of therapy.
      CONCLUSIONS: Pegylated IFN alpha-2b 1 MUg/kg/dose SQ weekly as maintenance
      therapy in children and adolescents with high-risk melanoma is feasible with
      tolerable toxicity and appears to yield higher exposures than nonpegylated IFN
      alpha-2b administered SQ TIW.

PMID- 27038396
TI  - Polyphenol-Rich Fraction from Larrea divaricata and its Main Flavonoid Quercetin
      3-Methyl Ether Induce Apoptosis in Lymphoma Cells Through Nitrosative Stress.
AB  - Larrea divaricata is a plant with antiproliferative principles. We have
      previously identified the flavonoid quercetin-3-methyl ether (Q-3-ME) in an ethyl
      acetate fraction (EA). Both the extract and Q-3-ME were found to be effective
      against the EL-4 T lymphoma cell line. However, the mechanism underlying the
      inhibition of tumor cell proliferation remains to be elucidated. In this work, we
      analyzed the role of nitric oxide (NO) in the induction of apoptosis mediated by
      Q-3-ME and EA. Both treatments were able to induce apoptosis in a concentration
      dependent and time-dependent manner. The western blot analysis revealed a
      sequential activation of caspases-9 and 3, followed by poly-(ADP-ribose)
      polymerase cleavage. EA and Q-3-ME lowered the mitochondrial membrane potential,
      showing the activation of the intrinsic pathway of apoptosis. Q-3-ME and EA
      increased NO production and inducible NO synthase expression in tumor cells. The
      involvement of NO in cell death was confirmed by the nitric oxide synthases
      inhibitor L-NAME. In addition, EA and Q-3-ME induced a cell cycle arrest in G0/G1
      phase. These drugs did not affect normal cell viability. This data suggested that
      EA and Q-3-ME induce an increase in NO production that would lead to the cell
      cycle arrest and the activation of the intrinsic pathway of apoptosis. Copyright
      (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27038397
TI  - Inborn error metabolic screening in individuals with nonsyndromic autism spectrum
      disorders.
AB  - AIM: To perform metabolic testing on 406 patients (age range 3-22y [mean 6.71, SD
      4.15], 343 males and 63 females) with nonsyndromic autism spectrum disorders
      (ASD) to assess the diagnostic yield. In addition, we reviewed our hospital's
      clinical database of 8500 patients who had undergone metabolic testing to be
      identified for inborn errors of metabolism (IEM), and described the
      characteristics of those with IEM and nonsyndromic ASD. METHOD:
      Neuropsychological evaluation included the Social Communication Questionnaire and
      Child Behavior Checklist. For metabolic testing/screening, urine samples were
      analyzed for the diagnosis of cerebral creatine deficiency syndromes, purine and
      pyrimidine disorders, amino acid metabolism defects, mucopolysaccharidoses, and
      organic acidurias. RESULTS: The 406 recruited participants fulfilled the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
      criteria of ASD. No biochemical evidence of a metabolic disorder was detected in
      any of the 406 patients studied. Concerning the retrospective evaluation from the
      8500 who had metabolic testing, 464 individuals had a diagnosis of an IEM (394
      without the diagnosis of ASD and 70 with ASD diagnosis). Only one individual with
      IEM had a diagnosis of nonsyndromic ASD at the time of the metabolic study; the
      metabolic testing had revealed diagnosis of urea-cycle disorder. INTERPRETATION:
      Metabolic testing should be considered in the work-up of individuals with
      syndromic ASD, but metabolic testing is not cost-effective for individuals with
      nonsyndromic ASD.

PMID- 27038398
TI  - Living Conditions, Low Socioeconomic Position, and Mortality in the Ibadan Study
      of Aging.
AB  - Objectives: Very little is known about socioeconomic differentials in mortality
      among persons surviving to old age in sub-Saharan Africa. We report on the impact
      of low socioeconomic position (SEP) on mortality over a 5-year observation period
      among community-dwelling older adults living in southwestern Nigeria. Method:
      Data are from a household multistage probability sample of 2,149 Yoruba Nigerians
      aged 65 years or older. We collected information on indices related to health and
      well-being at baseline (2003/2004). Socioeconomic positions were estimated using
      asset-based measures relevant to low income settings. Information on mortality
      was obtained by research supervisors in multiple waves (2007, 2008, and 2009).
      Associations between baseline covariates and mortality were explored using
      discrete time survival models and life tables. Results: We recorded 357 deaths
      over 5 years, or an annual mortality rate of 4.7% (95% CI = 4.2-5.2). Being 80
      years or older (HR = 1.6, 95% CI = 1.1-2.5) and belonging to the lowest SEP (HR =
      1.5, 95% CI = 1.1-2.1) were the main predictors of mortality. The significant
      effect of lowest SEP on mortality risk over the study period was independent of
      age, gender, education, rural or urban residence, weight, physical activity
      level, and social engagement. Conclusion: In this sample of older persons living
      in an economically disadvantaged context, we found persistent socioeconomic
      differentials in mortality estimated, conservatively, over 5 years.

PMID- 27038399
TI  - Coming Into Its Own? Developments and Challenges for Research on Aging in Africa.

PMID- 27038400
TI  - Screening for toxic phorbol esters in jerky pet treat products using LC-MS.
AB  - Since 2007, the U.S. FDA's Center for Veterinary Medicine (CVM) has been
      investigating reports of pets becoming ill after consuming jerky pet treats.
      Jerky used in pet treats contains glycerin, which can be made from vegetable oil
      or as a byproduct of biodiesel production. Because some biodiesel is produced
      using oil from Jatropha curcas, a plant that contains toxic compounds including
      phorbol esters, CVM developed a liquid chromatography-mass spectrometry (LC-MS)
      screening method to evaluate investigational jerky samples for the presence of
      these toxins. Results indicated that the samples analyzed with the new method did
      not contain Jatropha toxins at or above the lowest concentration tested. 

PMID- 27038401
TI  - An LC-MS/MS method for simultaneous determination of four flavonoids from Semen
      Oroxyli in rat plasma and its application to a pharmacokinetic study.
AB  - Semen Oroxyli, a Traditional Chinese Medicine, has many significant
      pharmacological activities such as analgesic, apoptotic, anti-inflammatory,
      anticancer, and immunostimulant activities. A sensitive and selective liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and
      validated for the simultaneous quantitation of four flavonoids (oroxin A, oroxin
      B, baicalin, and chrysin) of Semen Oroxyli in rat plasma. After the addition of
      internal standard, plasma samples were pretreated with acetonitrile via a single
      step protein precipitation. Chromatographic separation was performed on a Capcell
      Pak C18 column (100 mm * 2.0 mm, 5 MUm particles) with isocratic elution using a
      mobile phase of methanol and 2mM ammonium acetate buffer solution (75:25, v/v) at
      a flow rate of 0.45 mL/min. The analytes were detected without interference in
      the selection reaction monitoring mode with negative electrospray ionization. The
      validated method exhibited good linearity over a wide concentration range (r >=
      0.9958), and the lower limits of quantification were 1.0-5.5 ng/mL for all the
      analytes. The mean extraction recoveries of the analytes from rat plasma exceeded
      80.6%. The intra- and inter-day precisions at three QC levels were both less than
      11.5%, and the accuracies ranged from -6.2% to 10.3%. The LC-MS/MS method was
      successfully applied to a pharmacokinetic study of the four flavonoids in rat
      plasma after oral administration of Semen Oroxyli extract.

PMID- 27038402
TI  - Analysis of prasugrel active metabolite R-138727 in human plasma: a sensitive,
      highly selective and fast LC-MS/MS method.
AB  - A cost effective, sensitive, simple, and rapid high-performance liquid
      chromatography-tandem mass spectrometry method was developed and validated for
      the quantification of the prasugrel metabolite in human plasma. Following solid
      phase extraction, the analyte (prasugrel active metabolite; R-138727) and
      internal standard (emtricitabine) were separated using a mobile phase in an
      isocratic elution mode on a reverse phase C18 column and were analyzed by an LC
      MS/MS in the multiple reaction monitoring mode using the respective [M+H](+)
      ions, m/z 498.3-206.0 for R-138727 and m/z 248.2-130.1 for the internal standard.
      The assay exhibited a linear dynamic range of 0.2-120 ng/mL. The lower limit of
      quantification was 0.2 ng/mL with a relative standard deviation of 5.0%. This LC
      MS/MS method was validated with intra-batch and inter-batch precision and
      accuracy. Results for precision and accuracy are in range of 3.9-9.6% and 95.2
      102.2% respectively. This validated method is simple and repeatable to use in
      bioequivalence/pharmacokinetic studies.

PMID- 27038403
TI  - Simultaneous determination of itraconazole, hydroxy itraconazole, keto
      itraconazole and N-desalkyl itraconazole concentration in human plasma using
      liquid chromatography with tandem mass spectrometry.
AB  - A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS)
      assay was developed and validated for simultaneous determination of itraconazole
      (ITZ), hydroxy-itraconazole (OH-ITZ), keto-itraconazole (keto-ITZ) and N-desalkyl
      itraconazole (ND-ITZ) concentration in human plasma. One hundred and fifty
      microliters of human plasma were extracted using a solid-supported liquid
      extraction (SLE) method and the final extracts were analyzed using reverse-phase
      chromatography and positive electrospray ionization mass spectrometry. The
      standard curve range is 5-2500 ng/mL for ITZ and OH-ITZ and 0.4-200 ng/mL for
      keto-ITZ and ND-ITZ. The curve was fitted to a 1/x(2) weighted linear regression
      model for all analytes. The precision and accuracy of the LC-MS/MS assay based on
      the five analytical quality control (QC) levels were well within the acceptance
      criteria from both FDA and EMA guidance for bioanalytical method validation.
      Average extraction recovery was 97.4% for ITZ, 112.9% for OH-ITZ, 103.4% for keto
      ITZ, and 102.3% for ND-ITZ across their respective curve range. Matrix factor was
      close to 1.0 at both high and low QC levels of all 4 analytes, which indicates
      minimal ion suppression or enhancement in our validated assay. Itraconazole and
      all three metabolites are stable in human plasma for 145 days stored at -70 
      degrees C freezers. The validated assay was successfully applied to a clinical
      study, which has a drug-drug interaction (DDI) arm using ITZ as a cytochrome
      P450, family 3, subfamily A (CYP3A) inhibitor.

PMID- 27038404
TI  - Metabolic profile of esculin in rats by ultra high performance liquid
      chromatography combined with Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Esculin, a coumarin derivative found in Fraxinus rhynchophylla, has been reported
      to possess multiple biological activities. This present study is designed to
      investigate the metabolic profile of esculin in vivo based on ultra high
      performance liquid chromatography coupled to Fourier transform ion cyclotron
      resonance mass spectrometry (UHPLC-FT-ICR-MS) for the first time. After oral
      administration of esculin (100 mg/kg) for rats, plasma, urine, feces and bile
      samples were collected to screen metabolites. As a result, a total of 19
      metabolites (10 phase I metabolites and 9 phase II metabolites) were found and
      identified. Results showed that metabolic pathways of esculin included
      hydrolysis, dehydrogenation, hydroxylation, methylation, dehydrogenation,
      glucuronidation, sulfation, and glycine conjugation. It was also found that after
      oral administration of esculin, the esculin could be metabolized to esculetin in
      vivo via deglycosylation, and esculetin was found in all biological samples. This
      study also laid solid basis for in-depth development of esculin and provided
      important information for clarifying the biotransformation process of esculin in
      vivo.

PMID- 27038405
TI  - HIV Pharmacist's Impact on Inpatient Antiretroviral Errors.
AB  - OBJECTIVES: Transitions in care between out-patient and in-patient settings
      provide ample opportunity for medication errors to occur in HIV-infected
      patients. The purpose of this study was to examine the effectiveness of an HIV
      pharmacist monitoring service in decreasing antiretroviral medication errors in a
      large south central teaching hospital in the USA. METHODS: A retrospective,
      observational study was conducted to examine the frequency of antiretroviral
      medication errors in HIV-seropositive patients with hospital admissions between 1
      September 2011 and 30 September 2013 at a single tertiary care centre in
      Oklahoma. Patient assignment to the 12-month pre-intervention and intervention
      study periods was determined by admission date. Demographic, laboratory, and in
      patient medication data were collected. Bivariate analyses were conducted using
      chi2 analysis with the Yates correction factor for continuity to examine
      frequencies in specific antiretroviral classes and error categories. A
      multivariable Poisson regression was employed to examine the frequency of
      medication errors before and after initiation of the pharmacist service. RESULTS:
      Medication errors were examined in a total of 330 patient admissions during the 2
      year study period. A multivariable-adjusted decrease of 73.9% in the number of
      errors was observed between the pre-intervention and intervention periods (P <
      0.001). Patients on protease inhibitor regimens or with impaired renal function
      had 2.6-fold and 2.8-fold higher numbers of errors, respectively (P < 0.001).
      CONCLUSIONS: HIV pharmacist monitoring can decrease medication errors in HIV
      infected patients as they transition between out-patient and in-patient care.
      Patients receiving protease inhibitor-based therapy or with renal insufficiency
      are at higher risk for medication errors upon admission.

PMID- 27038406
TI  - Impact of Braun anastomosis on reducing delayed gastric emptying following
      pancreaticoduodenectomy: a prospective, randomized controlled trial.
AB  - BACKGROUND: The present study investigates the clinical impact of Braun
      anastomosis on delayed gastric emptying (DGE) after pylorus-preserving
      pancreaticoduodenectomy (PPPD). METHODS: From February 2013 to June 2014, 60
      patients were recruited for this randomized controlled trial. The incidence of
      DGE and its risk factors were analyzed according to whether or not Braun
      anastomosis was used after PPPD. RESULTS: Thirty patients were respectively
      enrolled in No-Braun group and Braun group. A comparative analysis between the
      two groups showed no differences in sex, diagnosis, operation time, hospital
      stay, or postoperative complications, including pancreatic fistula. Overall DGE
      developed in eight patients (26.7%) in the Braun group and in 14 patients (46.7%)
      in the No-Braun group (P = 0.108). However, clinically relevant DGE (grades B and
      C) was marginally more frequent in the No-Braun group (23.3% vs. 3.3%, P =
      0.052). In a multivariable analysis, No-Braun anastomosis was an independent risk
      factor for developing clinically relevant DGE (odds ratio = 16.489; 95%
      confidence interval: 1.287-211.195; P = 0.031). CONCLUSION: The overall DGE
      occurrence was not different between the two groups. However, No-Braun
      anastomosis was an independent risk factor for developing clinically relevant
      DGE.

PMID- 27038407
TI  - Environmental context for the terminal Ediacaran biomineralization of animals.
AB  - In terminal Ediacaran strata of South China, the onset of calcareous
      biomineralization is preserved in the paleontological transition from Conotubus
      to Cloudina in repetitious limestone facies of the Dengying Formation. Both
      fossils have similar size, funnel-in-funnel construction, and epibenthic
      lifestyle, but Cloudina is biomineralized, whereas Conotubus is not. To provide
      environmental context for this evolutionary milestone, we conducted a high
      resolution elemental and stable isotope study of the richly fossiliferous
      Gaojiashan Member. Coincident with the first appearance of Cloudina is a
      significant positive carbonate carbon isotope excursion (up to +60/00) and an
      increase in the abundance and (34) S composition of pyrite. In contrast,
      delta(34) S values of carbonate-associated sulfate remain steady throughout the
      succession, resulting in anomalously large (>700/00) sulfur isotope
      fractionations in the lower half of the member. The fractionation trend likely
      relates to changes in microbial communities, with sulfur disproportionation
      involved in the lower interval, whereas microbial sulfate reduction was the
      principal metabolic pathway in the upper. We speculate that the coupled
      paleontological and biogeochemical anomalies may have coincided with an increase
      in terrestrial weathering fluxes of sulfate, alkalinity, and nutrients to the
      depositional basin, which stimulated primary productivity, the spread of an
      oxygen minimum zone, and the development of euxinic conditions in subtidal and
      basinal environments. Enhanced production and burial of organic matter is thus
      directly connected to the carbon isotope anomaly, and likely promoted
      pyritization as the main taphonomic pathway for Conotubus and other soft-bodied
      Ediacara biotas. Our studies suggest that the Ediacaran confluence of ecological
      pressures from predation and environmental pressures from an increase in seawater
      alkalinity set the stage for an unprecedented geobiological response: the
      evolutionary novelty of animal biomineralization.

PMID- 27038409
TI  - NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY
      RESPONSE IN ANXIETY AND DEPRESSION.
AB  - BACKGROUND: Cognitive behavioral therapy (CBT) is a well-established treatment
      for anxiety and depression; however, response to CBT is heterogeneous across
      patients and many remain symptomatic after therapy, raising the need to identify
      prospective predictors for treatment planning. Altered neural processing of
      reward has been implicated in both depression and anxiety, and improving hedonic
      capacity is a goal of CBT. However, little is known about how neural response to
      reward relates to CBT outcomes in depression and anxiety. The current study used
      the reward positivity (RewP) event-related potential (ERP) component to examine
      whether neural reactivity to reward would predict CBT response in a sample of
      patients with anxiety without depression (n = 30) and comorbid anxiety and
      depression (CAD, n = 22). METHODS: Participants completed a guessing reward ERP
      paradigm before completing 12 weeks of standard CBT. RESULTS: The majority of the
      sample (68%; 35 out of 52 patients) responded to treatment, and those with a
      reduced RewP at baseline were more likely to respond to treatment. A reduced RewP
      was also associated with a greater pre-to-post CBT reduction in depressive
      symptoms among individuals with CAD, but not among individuals with pure anxiety.
      CONCLUSIONS: CBT may be most beneficial in reducing depressive symptoms for
      individuals who demonstrate decreased reward reactivity prior to treatment. CBT
      may target reward brain function, leading to greater improvement in symptoms.
      These effects may be strongest, and therefore most meaningful, for individuals
      with reward-processing deficits prior to treatment.

PMID- 27038408
TI  - GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION
      STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA
      WOMEN.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have made little progress in
      identifying variants linked to depression. We hypothesized that examining
      depressive symptoms and considering gene-environment interaction (GxE) might
      improve efficiency for gene discovery. We therefore conducted a GWAS and genome
      wide by environment interaction study (GWEIS) of depressive symptoms. METHODS:
      Using data from the SHARe cohort of the Women's Health Initiative, comprising
      African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined
      genetic main effects and GxE with stressful life events and social support. We
      also conducted a heritability analysis using genome-wide complex trait analysis
      (GCTA). Replication was attempted in four independent cohorts. RESULTS: No SNPs
      achieved genome-wide significance for main effects in either discovery sample.
      The top signals in African Americans were rs73531535 (located 20 kb from GPR139,
      P = 5.75 * 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 * 10(-7) ). In
      Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P =
      2.44 * 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 * 10(-7) ). In the GEWIS
      with stressful life events, one interaction signal was genome-wide significant in
      African Americans (rs4652467; P = 4.10 * 10(-10) ; located 14 kb from CEP350).
      This interaction was not observed in a smaller replication cohort. Although
      heritability estimates for depressive symptoms and stressful life events were
      each less than 10%, they were strongly genetically correlated (rG = 0.95),
      suggesting that common variation underlying self-reported depressive symptoms and
      stressful life event exposure, though modest on their own, were highly
      overlapping in this sample. CONCLUSIONS: Our results underscore the need for
      larger samples, more GEWIS, and greater investigation into genetic and
      environmental determinants of depressive symptoms in minorities.

PMID- 27038410
TI  - ALTERED DEFAULT MODE NETWORK (DMN) RESTING STATE FUNCTIONAL CONNECTIVITY
      FOLLOWING A MINDFULNESS-BASED EXPOSURE THERAPY FOR POSTTRAUMATIC STRESS DISORDER
      (PTSD) IN COMBAT VETERANS OF AFGHANISTAN AND IRAQ.
AB  - BACKGROUND: Recent studies suggest that mindfulness may be an effective component
      for posttraumatic stress disorder (PTSD) treatment. Mindfulness involves practice
      in volitional shifting of attention from "mind wandering" to present-moment
      attention to sensations, and cultivating acceptance. We examined potential neural
      correlates of mindfulness training using a novel group therapy (mindfulness-based
      exposure therapy (MBET)) in combat veterans with PTSD deployed to Afghanistan
      (OEF) and/or Iraq (OIF). METHODS: Twenty-three male OEF/OIF combat veterans with
      PTSD were treated with a mindfulness-based intervention (N = 14) or an active
      control group therapy (present-centered group therapy (PCGT), N = 9). Pre-post
      therapy functional magnetic resonance imaging (fMRI, 3 T) examined resting-state
      functional connectivity (rsFC) in default mode network (DMN) using posterior
      cingulate cortex (PCC) and ventral medial prefrontal cortex (vmPFC) seeds, and
      salience network (SN) with anatomical amygdala seeds. PTSD symptoms were assessed
      at pre- and posttherapy with Clinician Administered PTSD Scale (CAPS). RESULTS:
      Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but
      effect was not significantly different from PCGT (d = 0.46). Increased DMN rsFC
      (PCC seed) with dorsolateral dorsolateral prefrontal cortex (DLPFC) regions and
      dorsal anterior cingulate cortex (ACC) regions associated with executive control
      was seen following MBET. A group * time interaction found MBET showed increased
      connectivity with DLPFC and dorsal ACC following therapy; PCC-DLPFC connectivity
      was correlated with improvement in PTSD avoidant and hyperarousal symptoms.
      CONCLUSIONS: Increased connectivity between DMN and executive control regions
      following mindfulness training could underlie increased capacity for volitional
      shifting of attention. The increased PCC-DLPFC rsFC following MBET was related to
      PTSD symptom improvement, pointing to a potential therapeutic mechanism of
      mindfulness-based therapies.

PMID- 27038411
TI  - STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER:
      ASSOCIATIONS WITH FKBP5.
AB  - BACKGROUND: The integrity of connections between the hippocampus and the anterior
      cingulate cortex (ACC) is critical for adaptive cognitive and emotional
      processing; these connections may be compromised in posttraumatic stress disorder
      (PTSD). However, there is a lack of PTSD research that combines structural and
      functional connectivity data, and no studies have examined whether abnormal ACC
      hippocampal connectivity is associated with genetic variability, particularly for
      polymorphisms of a gene that has been previously associated with PTSD, FKBP5.
      This was the goal of the present study. METHODS: Fifty-four women with and
      without PTSD underwent diffusion tensor imaging and resting-state MRI.
      Probabilistic tractography was used to examine ACC-hippocampal structural
      connectivity; mean fractional anisotropy (FA) values were extracted from
      connectivity streamlines, which represent the cingulum bundle. Genotype data were
      collected for a single nucleotide polymorphism (SNP) of FKBP5, rs1360780.
      RESULTS: Participants with PTSD demonstrated poorer structural connectivity
      (lower cingulum FA) compared to traumatized controls (F1, 50 = 6.77, P < .05). An
      interaction of FKBP5 genotype and diagnostic group was also observed (F1, 37 =
      4.52, P = .04), indicating lower cingulum FA in carriers of two risk alleles for
      this SNP, compared to other diagnostic and genotype groups. Carriers of two FKBP5
      risk alleles also demonstrated poorer hippocampus-ACC connectivity at rest (P <
      .05). When cingulum FA was used a regressor in a brain-wide, seed-based
      regression analysis, significant associations were found between the hippocampus
      and dorsal regions of the ACC (P < .05). CONCLUSIONS: Individuals with PTSD
      demonstrated compromised structural connectivity of the hippocampus-ACC pathway.
      Altered hippocampus-ACC connectivity may represent a highly salient intermediate
      neural phenotype for PTSD.

PMID- 27038413
TI  - Impact of Membrane-Induced Particle Immobilization on Seeded Growth Monitored by
      In Situ Liquid Scanning Transmission Electron Microscopy.
AB  - In situ liquid cell scanning transmission electron microscopy probes seeded
      growth in real time. The growth of Pd on Au nanocubes is monitored as a model
      system to compare growth within a liquid cell and traditional colloidal
      synthesis. Different growth patterns are observed due to seed immobilization and
      the highly reducing environment within the liquid cell. 

PMID- 27038412
TI  - EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND INTERNALIZING
      PSYCHOPATHOLOGY.
AB  - BACKGROUND: DNA methylation of the SKA2 gene has recently been implicated as a
      biomarker of suicide risk and posttraumatic stress disorder (PTSD). To examine
      the specificity and reliability of these findings, we examined associations
      between SKA2 DNA methylation, broad dimensions of psychiatric symptoms, and
      suicide phenotypes in adults with high levels of trauma exposure. METHODS: A
      total of 466 White, non-Hispanic veterans and their intimate partners (65% male)
      underwent clinical assessment and had blood drawn for genotyping and methylation
      analysis. DNA methylation of the CpG locus cg13989295 and genotype at the
      methylation-associated single-nucleotide polymorphism (SNP) rs7208505 were
      examined in relation to current and lifetime PTSD, internalizing and
      externalizing psychopathology, and suicide phenotypes (ideation, plans, and
      attempts). RESULTS: DNA methylation at the previously implicated SKA2 CpG locus
      (cg13989295) was associated with current and lifetime symptoms of internalizing
      (but not externalizing) disorders. SKA2 methylation levels also predicted higher
      rates of current suicidal thoughts and behaviors, even after including well
      established psychiatric risk factors for suicide in the model. Associations
      between PTSD and SKA2 were not significant, and genetic variation at the
      methylation-associated SNP (rs7208505) was not related to any of the phenotypes
      examined. CONCLUSIONS: SKA2 methylation may index a general propensity to
      experience stress-related psychopathology, including internalizing disorders and
      suicidal thoughts and behaviors. This study demonstrates that SKA2 methylation
      levels explain unique variance in suicide risk not captured by clinical symptom
      interviews, providing further evidence of its potential utility as a biomarker of
      suicide risk and stress-related psychopathology.

PMID- 27038414
TI  - Increased grip strength with sodium-glucose cotransporter 2.

PMID- 27038415
TI  - Fryns Syndrome Associated with Recessive Mutations in PIGN in two Separate
      Families.
AB  - Fryns syndrome is an autosomal recessive condition characterized by congenital
      diaphragmatic hernia (CDH), dysmorphic facial features, distal digital
      hypoplasia, and other associated malformations, and is the most common syndromic
      form of CDH. No gene has been associated with this condition. Whole-exome
      sequence data from two siblings and three unrelated individuals with Fryns
      syndrome were filtered for rare, good quality, coding mutations fitting a
      recessive inheritance model. Compound heterozygous mutations in PIGN were
      identified in the siblings, with appropriate parental segregation: a novel STOP
      mutation (c.1966C>T: p.Glu656X) and a rare (minor allele frequency <0.001) donor
      splice site mutation (c.1674+1G>C) causing skipping of exon 18 and utilization of
      a cryptic acceptor site in exon 19. A further novel homozygous STOP mutation in
      PIGN (c.694A>T: p.Lys232X) was detected in one unrelated case. All three variants
      affected highly conserved bases. The two remaining cases were negative for PIGN
      mutations. Mutations in PIGN have been reported in cases with multiple congenital
      anomalies, including one case with syndromic CDH. Fryns syndrome can be caused by
      recessive mutations in PIGN. Whether PIGN affects other syndromic and non
      syndromic forms of CDH warrants investigation.

PMID- 27038416
TI  - Effects of velocity loss during resistance training on athletic performance,
      strength gains and muscle adaptations.
AB  - We compared the effects of two resistance training (RT) programs only differing
      in the repetition velocity loss allowed in each set: 20% (VL20) vs 40% (VL40) on
      muscle structural and functional adaptations. Twenty-two young males were
      randomly assigned to a VL20 (n = 12) or VL40 (n = 10) group. Subjects followed an
      8-week velocity-based RT program using the squat exercise while monitoring
      repetition velocity. Pre- and post-training assessments included: magnetic
      resonance imaging, vastus lateralis biopsies for muscle cross-sectional area
      (CSA) and fiber type analyses, one-repetition maximum strength and full load
      velocity squat profile, countermovement jump (CMJ), and 20-m sprint running. VL20
      resulted in similar squat strength gains than VL40 and greater improvements in
      CMJ (9.5% vs 3.5%, P < 0.05), despite VL20 performing 40% fewer repetitions.
      Although both groups increased mean fiber CSA and whole quadriceps muscle volume,
      VL40 training elicited a greater hypertrophy of vastus lateralis and intermedius
      than VL20. Training resulted in a reduction of myosin heavy chain IIX percentage
      in VL40, whereas it was preserved in VL20. In conclusion, the progressive
      accumulation of muscle fatigue as indicated by a more pronounced repetition
      velocity loss appears as an important variable in the configuration of the
      resistance exercise stimulus as it influences functional and structural
      neuromuscular adaptations.

PMID- 27038417
TI  - Late sequelae of left ventricular assist device infection presenting after heart
      transplant.
AB  - The long-term use of left ventricular assist devices (LVADs) is becoming more
      common among the end-stage heart failure population. At the time of heart
      transplantation, most of the LVAD is removed, but some of its components might be
      retained. Retained LVAD prosthetic material can lead to serious infection post
      heart transplant. We report 4 such cases. Our goal is to highlight the importance
      of complete prosthetic material removal at the time of cardiac transplant to
      prevent late-onset infection, especially in patients with preceding infection,
      but also in patients without evidence of LVAD infection prior to orthotopic heart
      transplantation.

PMID- 27038418
TI  - Conversion of human M-CSF macrophages into foam cells reduces their
      proinflammatory responses to classical M1-polarizing activation.
AB  - BACKGROUND: In atherosclerotic lesions, cholesterol-laden macrophage foam cells
      are formed and exposed to M1- and M2-polarizing factors. However, the effects of
      the polarizing factors on the proinflammatory and the anti-inflammatory potential
      of foam cells are not known. OBJECTIVE: To investigate the effects of M1- and M2
      polarizing factors on the expression of pro- and anti-inflammatory genes in
      cultured human macrophage foam cells. METHODS AND RESULTS: Human monocytes were
      differentiated into macrophages in the presence of M-CSF, and then converted into
      cholesterol-loaded foam cells by incubation with acetylated LDL. The generated
      macrophages and foam cells were polarized into the M1 phenotype by classical
      activation with LPS and IFN-gamma, or into the M2 phenotype by alternative
      activation with IL-4. When subjected to the M1-polarizing factors, the
      macrophages responded by typical upregulation of several key proinflammatory
      genes (TNFA, IL1B, CXCL8, CCL19, and COX2), while the anti-inflammatory genes
      (MRC1, CCL17, and IL10) displayed variable responses. The foam cells, again,
      showed a weaker response to the M1-polarizing factors, as indicated by reduced
      upregulation of the proinflammatory genes, reduced secretion of TNF-alpha, and a
      trend towards lower NF-kappaB activity. When subjected to alternative M2
      polarization, both macrophages and foam cells responded by a typical upregulation
      of the anti-inflammatory genes, which was of equal magnitude in both cell types.
      CONCLUSIONS: Conversion of cultured human macrophages into foam cells suppresses
      their proinflammatory responses to M1-polarizing factors. Thus, in M1-polarizing
      microenvironments of atherosclerotic lesions, foam cell formation may locally
      weaken the macrophage-dependent inflammatory component of atherogenesis.

PMID- 27038420
TI  - Accurate quantification of atherosclerotic plaque volume by 3D vascular
      ultrasound using the volumetric linear array method.
AB  - INTRODUCTION: Direct quantification of atherosclerotic plaque volume by three
      dimensional vascular ultrasound (3DVUS) is more reproducible than 2DUS-based
      three-dimensional (2D/3D) techniques that generate pseudo-3D volumes from summed
      2D plaque areas; however, its accuracy has not been reported. We aimed to
      determine 3DVUS accuracy for plaque volume measurement with special emphasis on
      small plaques (a hallmark of early atherosclerosis). METHODS: The in vitro study
      consisted of nine phantoms of different volumes (small and medium-large) embedded
      at variable distances from the surface (superficial vs. >5 cm-depth) and
      comparison of 3DVUS data generated using a novel volumetric-linear array method
      with the real phantom volumes. The in vivo study was undertaken in a rabbit model
      of atherosclerosis in which 3DVUS and 2D/3D volume measurements were correlated
      against gold-standard histological measurements. RESULTS: In the in vitro
      setting, there was a strong correlation between 3DVUS measures and real phantom
      volume both for small (3.0-64.5 mm(3) size) and medium-large (91.1-965.5 mm(3)
      size) phantoms embedded superficially, with intraclass correlation coefficients
      (ICC) of 0.99 and 0.98, respectively; conversely, when phantoms were placed at >5
      cm, the correlation was only moderate (ICC = 0.67). In the in vivo setting there
      was strong correlation between 3DVUS-measured plaque volumes and the histological
      gold-standard (ICC = 0.99 [4.02-92.5 mm(3) size]). Conversely, the correlation
      between 2D/3D values and the histological gold standard (sum of plaque areas) was
      weaker (ICC = 0.87 [49-520 mm(2) size]), with large dispersion of the differences
      between measurements in Bland-Altman plots (mean error, 79.2 mm(2)). CONCLUSIONS:
      3DVUS using the volumetric-linear array method accurately measures plaque
      volumes, including those of small plaques. Measurements are more accurate for
      superficial arterial territories than for deep territories.

PMID- 27038419
TI  - Fetuin-A, glycemic status, and risk of cardiovascular disease: The Multi-Ethnic
      Study of Atherosclerosis.
AB  - AIMS: Fetuin-A is a hepatic secretory protein that both promotes insulin
      resistance and inhibits arterial calcification. Previous studies have suggested
      that the association of fetuin-A with incident cardiovascular disease (CVD) might
      be modified by glycemic status. METHODS AND RESULTS: We conducted a case-cohort
      study of fetuin-A and incident non-fatal CVD nested in the Multi-Ethnic Study of
      Atherosclerosis with follow-up from 2000 to 2007. Fetuin-A concentrations were
      measured from baseline serum samples among 2505 randomly selected subcohort
      members and 142 incident cases. In weighted multivariable Cox regression models,
      no association was observed between fetuin-A and incident CVD in the total study
      population (HR per SD = 1.01; 95% CI: 0.84, 1.23). Although associations with CVD
      events were not statistically significant within categories of glycemic status,
      our results tended to support the interaction with glycemic status observed in
      other studies, with a positive trend restricted to participants with impaired
      fasting glucose or diabetes (HR per SD = 1.20; 95% CI: 0.89, 1.63) and an inverse
      trend among normoglycemic individuals (HR = 0.89; 95% CI: 0.69-1.13) (p
      interaction = 0.04). In addition, we observed significant interaction between
      fasting glucose and fetuin-A when both were treated continuously in the subset of
      participants not using diabetes medication (p-interaction = 0.006). CONCLUSION:
      Our results suggest that fetuin-A is not associated with an overall risk of CVD,
      but support prior evidence indicating that the association might be modified by
      glycemic status.

PMID- 27038421
TI  - Mild heat stress enhances differentiation and proliferation of Japanese quail
      myoblasts and enhances slow muscle fiber characteristics.
AB  - The objective of this study was to investigate the effect of mild heat stress on
      muscle fiber hyperplastic and hypertrophic growth in quail primary myogenic cells
      to better understand the mechanisms leading to increased skeletal muscle
      development in avian embryos incubated at a higher temperature. Compared to
      control cultures maintained at 37 degrees C, incubation at 39 degrees C enhanced
      myotube length (P < 0.01) and diameter (P < 0.001) at 3 days after
      differentiation (D3). This enlargement of the myotubes incubated at 39 degrees C
      can be explained by differences in the fusion index (56.7 vs. 46.2%, P < 0.05)
      and nuclei number per myotube (18.1 vs. 10.8, P < 0.001) compared to the control
      cells at D3. Additionally, a higher density of myotubes at D3 in cultures exposed
      to a higher temperature were related to higher levels of Pax-7 (P < 0.05)
      compared to the control cells incubated continuously at 37 degrees C. These
      results indicated a higher proliferative capacity in cells exposed to mild heat
      stress compared to the control cells. On the other hand, mild heat stress
      enhanced protein levels of slow myosin heavy chain isoform (P < 0.01) and
      cytochrome c oxidase subunit IV (P < 0.01) compared to the control cells at D3.
      These discrepancies in protein expression indicated maintenance of slow muscle
      fiber type characteristics in myotubes incubated at 39 degrees C. Our results
      suggest that mild heat stress plays a significant role in myogenic mechanisms
      related to muscle mass and development. 

PMID- 27038422
TI  - Effect of the addition of beta-mannanase on the performance, metabolizable
      energy, amino acid digestibility coefficients, and immune functions of broilers
      fed different nutritional levels.
AB  - Three experiments were conducted to evaluate the effect of beta-mannanase BM:
      supplementation on the performance, metabolizable energy, amino acid
      digestibility, and immune function of broilers. A total of 1,600 broilers were
      randomly distributed in a 4 * 2 factorial arrangement (4 nutritional levels * 0
      or 500 g/ton BM), with 10 replicates and 20 broilers per pen. The same design was
      used in the energy and digestibility experiments with 8 and 6 replicates,
      respectively, and 6 broilers per pen. The nutritional levels : NL : were
      formulated to meet the nutritional requirements of broilers : NL1 : ; reductions
      of 100 kcal metabolizable energy : NL2 : ; 3% of the total amino acids (NL3); and
      100 kcal metabolizable energy and 3% total amino acids (NL4) from NL1. The serum
      immunoglobulin (Ig) concentration was determined in two broilers per pen, and
      these broilers were slaughtered to determine the relative weight of spleen,
      thymus, and bursa of Fabricius. Throughout the experiment, the lower nutritional
      levels reduced (P < 0.05) body weight gain : BWG : and increased (P < 0.05) feed
      conversion : FCR : for the NL4 treatment. The BM increased (P < 0.05) the BWG
      values and improved (P < 0.05) the FCR of the broilers. The apparent
      metabolizable energy corrected for nitrogen balance (AMEn) values were reduced (P
      < 0.05) for NL2 and NL3. The BM increased (P < 0.05) the AMEn values and reduced
      (P < 0.05) the excreted nitrogen. NL3 and NL4 reduced (P < 0.05) the true ileal
      digestibility coefficients (TIDc) of the amino acids cystine and glycine, and BM
      increased (P < 0.05) the TIDc for all amino acids. The addition of BM reduced (P
      < 0.05) the relative weights of the spleen and bursa. NL2 increased (P < 0.05)
      the Ig values, whereas BM reduced (P < 0.05) the serum IgA, IgG, and IgM values
      of the broilers. This study indicates that using suboptimal nutrient levels leads
      to losses in production parameters, whereas BM-supplemented diets were effective
      in improving performance, energy values, and TIDc levels of amino acids and
      immune response of broilers. 

PMID- 27038423
TI  - The effect of chicken blood and its components on wastewater characteristics and
      sewage surcharges.
AB  - Local wastewater treatment authorities levy surcharges from their non-residential
      customers that are based, in part, on the concentration of various pollutants in
      the customer's wastewater. Blood has long been recognized as the most potent
      contributor to pollutant loads in chicken processing plant wastewater.
      Quantification of the impact of blood on wastewater characteristics and sewage
      surcharges is hindered by lack of information on specific characteristics of
      chicken blood, and by the highly variable methods used by local authorities for
      calculating surcharges. In this study, the most commonly used wastewater
      characteristics are determined for whole chicken blood as well as its individual
      components. The characteristics measured include biochemical oxygen demand,
      chemical oxygen demand, total suspended solids, fats oil and grease, total
      Kjeldahl nitrogen, ammonia, and total phosphorus. Sewage surcharge calculation
      methods were collected from 71 local wastewater authorities. The results show all
      components of the blood to be extremely high-strength pollutants. The impact of
      blood on sewage surcharges is shown to be highly variable depending on the rates
      applied by the local authority. 

PMID- 27038424
TI  - Impact of oral Lactobacillus acidophilus gavage on rooster seminal and cloacal
      Lactobacilli concentrations.
AB  - The use of antibiotics in poultry is being heavily scrutinized, therefore
      alternatives such as probiotics are being investigated. Lactobacilli spp. are a
      commonly used bacteria in formulating probiotics, and the addition of
      Lactobacilli to broiler diets has demonstrated increased growth rates, stimulated
      immune systems, and reduced pathogen loads in the gastro-intestinal tract ( GI: )
      tract. However, previous research has shown that when rooster semen is directly
      exposed to Lactobacillus acidophilus (L. acidophilus) sperm quality is reduced.
      Therefore, the objective of the current study was to determine if oral
      administration of L. acidophilus increases the concentration of Lactobacilli in
      semen as well as the cloaca. A total of 30 roosters were used: 15 roosters were
      gavaged with 1X PBS (Control) and 15 roosters were gavaged with 10(7) cfu/mL of
      L. acidophilus (Treated). All roosters were gavaged for 14 consecutive days.
      Semen was collected on a 3 d interval, and cloacal swabs were collected on a 2 d
      interval, beginning on the first day prior to oral administration. Semen and
      cloacal swabs were serial diluted, and 100 MUL of each dilution was then plated
      on Man, Rogosa, Sharpe ( MRS: ) agar plates. All plates were incubated for 48 h
      at 37 degrees C under anaerobic conditions and counted. All Lactobacilli counts
      were first log transformed, then log transformed (day 0) pre-counts were
      subtracted from the log transformed day counts providing log differences for the
      analysis. Seminal Lactobacilli counts were not altered by treatments. However,
      the main effect of treatment (P = 0.026) for cloacal counts indicated that
      roosters gavaged with Lactobacilli yielded higher counts than the controls.
      Additionally, cloaca samples also demonstrated a treatment by day interaction
      trend (P = 0.082), where Lactobacilli was higher in the L. acidophilus gavaged
      roosters than the controls only on days 3, 5, 13, and 15. In conclusion, the
      addition of L. acidophilus to the male breeder diet over extended periods may
      increase concentrations of Lactobacilli in the cloaca even higher than the
      concentrations observed in this study. If Lactobacilli reaches high enough
      concentrations in the cloaca, then sperm quality may be impacted which could lead
      to poor fertility within the breeder flock. 

PMID- 27038425
TI  - 1,1-Dilithioethylene: Toward Spectroscopic Identification of the Definitive
      Singlet Ground Electronic State of a Peculiar Structure.
AB  - 1,1-Dilithioethylene is a prototypical carbon-lithium compound that is not known
      experimentally. All low-lying singlet and triplet structures of interest were
      investigated by using high-level theoretical methods with correlation-consistent
      basis sets up to pentuple zeta. The coupled cluster methods adopted included up
      to full triple excitations and perturbative quadruples. In contrast to earlier
      studies that predicted the twisted C2v triplet to be the ground state, we found a
      peculiar planar Cs singlet ground state in the present research. The lowest
      excited electronic state of 1,1-dilithioethylene, the twisted Cs triplet, was
      found to lie 9.0 kcal mol(-1) above the ground state by using energy
      extrapolation to the complete basis set limit. For the planar Cs singlet and
      twisted Cs triplet states of 1,1-dilithioethylene, anharmonic vibrational
      frequencies were reported on the basis of second-order vibrational perturbation
      theory. The remarkably low (2050 cm(-1) ) C-H stretching fundamental (the C-H
      bond near the bridging lithium) of the singlet state was found to have very
      strong infrared intensity. These highly reliable theoretical findings may assist
      in the long-sought experimental identification of 1,1-dilithioethylene. Using
      natural bond orbital analysis, we found that lithium bridging structures were
      strongly influenced by electrostatic effects. All carbon-carbon linkages
      corresponded to conventional double bonds.

PMID- 27038426
TI  - Impact of Bacillus cereus NRKT on grape ripe rot disease through resveratrol
      synthesis in berry skin.
AB  - BACKGROUND: Vine growers are faced with the difficult problem of how to control
      grape ripe rot disease in vineyards because of fear of accumulation of pesticide
      residues on grape berries near harvest. Biological control is an alternative non
      hazardous technique to control the diseases. RESULTS: Application of resveratrol
      synthesis-promoting bacterium, Bacillus cereus strain NRKT, reduced the incidence
      of grape ripe rot disease caused by Colletotrichum gloeosporioides in a vineyard.
      The application of NRKT to berry bunches upregulated the gene expression of
      stilbene synthase, a key enzyme for resveratrol synthesis in berry skins, thereby
      promoting resveratrol synthesis in berry skins. CONCLUSION: The potential use of
      NRKT in vineyards is expected to contribute to the increase in resveratrol
      content in berry skins, thereby protecting grape berries against fungal diseases.
      (c) 2016 Society of Chemical Industry.

PMID- 27038427
TI  - N-acetyl cysteine protects cells from chondrocyte death induced by local
      anesthetics.
AB  - Local anesthetics (LA) are among the drugs most frequently used for
      musculoskeletal problems, in procedures ranging from diagnosis to postoperative
      pain control. Chondrocyte toxicity induced by LA is an emerging area of concern.
      The purpose of this study was to determine whether N-acetyl cysteine (NAC), an
      antioxidant, will exert cytoprotective effects against chondrocyte death induced
      by LA. Primary cultured human chondrocytes were used for this study. This study
      used control, NAC, LA, and NAC-LA groups. Cytotoxicity was induced in the LA
      subgroups and their paired NAC-LA subgroups through exposure to ropivacaine
      (0.075%), bupivacaine (0.05%), or lidocaine (0.2%) for 24 h. The NAC-LA subgroups
      were exposed to 10 mM NAC for 1 h, before LA exposure. These study groups were
      evaluated for rates of cell viability, apoptosis, necrosis, intracellular ROS
      production, and caspase-3/7 activity. Cell viability in all LA subgroups was
      significantly lower than in the control group (p < 0.001). Cell viability in the
      NAC-LA subgroups was significantly higher than in their paired LA subgroups (p <
      0.001). In the LA subgroups, rates of apoptosis and necrosis, intracellular ROS
      production, and caspase-3/7 activity were significantly higher than in the
      control group (p <= 0.029). In the NAC-LA subgroups, rates of apoptosis and
      necrosis, intracellular ROS production, and caspase-3/7 activity were
      significantly lower than in their paired LA subgroups (p <= 0.023). These results
      indicate that N-acetyl cysteine, an antioxidant, has cytoprotective effects
      against LA-induced toxicity to chondrocytes in vitro. (c) 2016 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:297-303,
      2017.

PMID- 27038428
TI  - NIPT and Informed Consent: an Assessment of Patient Understanding of a Negative
      NIPT Result.
AB  - Since becoming clinically available in 2011, the use of noninvasive prenatal
      testing (NIPT) to screen for fetal aneuploidy has continued to increase. However,
      it has been questioned whether the education of patients undergoing NIPT
      consistently meets informed consent standards. We sought to evaluate patients'
      basic understanding of NIPT, such as conditions assessed and accuracy. In
      addition, we investigated patient self-assessment of NIPT knowledge and
      satisfaction with the testing process. We distributed an anonymous paper survey
      to pregnant women during prenatal visits following a negative NIPT result. The
      survey assessed patient NIPT knowledge, gathered pregnancy-specific and
      demographic information, and allowed respondents to rank their basic
      understanding of NIPT and provide written feedback about the testing process. A
      total of 95 completed and 3 partially completed surveys were returned.
      Participants scored lowest on knowledge questions involving whether a negative
      NIPT result ensures a healthy baby or eliminates the possibility of Down
      syndrome. Most perceived themselves to have a good basic understanding of NIPT
      and two-thirds of the written feedback proposed no changes to NIPT
      administration. Overall, most patients appear satisfied with their understanding
      of NIPT and the testing process, yet they may not fully appreciate the
      limitations of this screening method.

PMID- 27038429
TI  - Vitiligo: a potential autoimmune sequela of DRESS syndrome.

PMID- 27038430
TI  - Early tooth loss in end-stage renal disease patients on haemodialysis.
AB  - OBJECTIVE: This article sets out to evaluate the prevalence and aetiopathogenesis
      of edentulism in patients on haemodialysis. SUBJECTS AND METHODS: The study group
      comprised 44 adult patients with end-stage renal disease (ESRD) on haemodialysis.
      A control group was formed of 44 individuals matched for age and sex and with a
      glomerular filtration rate >90 ml min(-1) . All participants underwent intra-oral
      examination, gathering information on dental and periodontal status, and a saliva
      sample was taken to determine saliva debit and its biochemical composition.
      RESULTS: The average number of missing teeth was higher in ESRD patients than in
      controls (P = 0.018). Six (13.6%) fully edentulous individuals were detected in
      the study group and 1 (2.2%) in the control group. Some of the clinical and
      biochemical variables with statistically significant differences between the
      study group and the control group showed a significant relationship with the
      number of missing teeth, but the depth of the periodontal pockets presented the
      highest coefficient of determination (OR = 3511.1; 95%CI = 82.2-6834.3; P <
      0.001; R(2)  = 0.827). CONCLUSIONS: Premature tooth loss is common in
      haemodialysis patients. Although the aetiology and pathogenesis of this finding
      has still not been fully clarified, it appears that severe periodontal disease
      may play a relevant role.

PMID- 27038431
TI  - Effect of mixed alloy combinations on fretting corrosion performance of spinal
      screw and rod implants.
AB  - Spinal implants are made from a variety of materials to meet the unique
      mechanical demands of each application. However, the medical device community has
      raised concern about mixing dissimilar metals in an implant because of fear of
      inducing corrosion. There is a lack of systematic studies on the effects of
      mixing metals on performance of spinal implants, especially in fretting corrosion
      conditions. Hence, the goal was to determine whether mixing stainless steel
      (SS316L), titanium alloy (Ti6Al4V) and cobalt chromium (CoCrMo) alloy components
      in a spinal implant leads to any increased risk of corrosion degradation. Spinal
      constructs consisting of single assembly screw-connector-rod components were
      tested using a novel short-term cyclic fretting corrosion test method. A total of
      17 alloy component combinations (comprised of SS316L, Ti6Al4V-anodized and CoCrMo
      alloy for rod, screws and connectors) were tested under three anatomic
      orientations. Spinal constructs having all SS316L were most susceptible to
      fretting-initiated crevice corrosion attack and showed higher average fretting
      currents (~25 - 30 uA), whereas constructs containing all Ti6Al4V components were
      less susceptible to fretting corrosion with average fretting currents in the
      range of 1 - 6 uA. Mixed groups showed evidence of fretting corrosion but they
      were not as severe as all SS316L group. SEM results showed evidence of severe
      corrosion attack in constructs having SS316L components. There also did not
      appear to be any galvanic effects of combining alloys together. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1169-1177,
      2017.

PMID- 27038432
TI  - Enhancement of biogas production from food waste and sewage sludge -
      Environmental and economic life cycle performance.
AB  - Management of municipal solid waste is an efficient method to increase resource
      efficiency, as well as to replace fossil fuels with renewable energy sources due
      to that (1) waste to a large extent is renewable as it consists of food waste,
      paper, wood etc. and (2) when energy and materials are recovered from waste
      treatment, fossil fuels can be substituted. In this paper results from a
      comprehensive system study of future biological treatment of readily degradable
      waste in two Swedish regions are presented. Different collection and separation
      systems for food waste in households have been applied as well as technical
      improvements of the biogas process as to reduce environmental impact. The results
      show that central sorting of a mixed fraction into recyclables, combustibles,
      biowaste and inert is a competitive option compared to source separation. Use of
      pellets is beneficial compared to direct spreading as fertiliser. Fuel pellets
      seem to be the most favourable option, which to a large extent depends on the
      circumstances in the energy system. Separation and utilisation of nitrogen in the
      wet part of the digestion residue is made possible with a number of technologies
      which decreases environmental impact drastically, however to a substantial cost
      in some cases. 

PMID- 27038433
TI  - Rapid degradation of phenol by ultrasound-dispersed nano-metallic particles
      (NMPs) in the presence of hydrogen peroxide: A possible mechanism for phenol
      degradation in water.
AB  - The present study was carried out to investigate the degradation of phenol by
      ultrasonically dispersed nano-metallic particles (NMPs) in an aqueous solution of
      phenol. Leaching liquor from automobile shredder residue (ASR) was used to obtain
      the NMPs. The prepared NMPs were analyzed by scanning electron microscopy (SEM),
      X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy
      (FTIR), and by X-ray diffraction (XRD). The SEM images show that the diameters of
      the NMPs were less than 50 nm. An SEM-EDX elemental analysis reveals that Fe was
      the most commonly found element (weight %) in the NMPs. The FTIR and XRD peaks
      indicate the presence of metals oxides on the surfaces of the NMPs. The results
      of the XPS analysis indicate that various elements (e.g., C, O, Zn, Cu, Mn, Fe)
      are present on the surfaces of the NMPs. The effects of the NMP dose, the initial
      solution pH, and of different concentrations of phenol and H2O2 on the phenol
      degradation characteristics were evaluated. The results of this study demonstrate
      that phenol degradation can be improved by increasing the amount of NMPs, whereas
      it is reduced with an increase in the phenol concentration. The degradation of
      phenol by ultrasonically dispersed NMPs followed the pseudo-first-order kinetics.
      The probable mechanism of phenol degradation by ultrasonically dispersed NMPs was
      the oxidation of phenol caused by the hydroxyl radicals produced during the
      reaction between H2O2 and the NMPs during the ultrasonication process.

PMID- 27038434
TI  - Acclimation of the crucifer Eutrema salsugineum to phosphate limitation is
      associated with constitutively high expression of phosphate-starvation genes.
AB  - Eutrema salsugineum, a halophytic relative of Arabidopsis thaliana, was subjected
      to varying phosphate (Pi) treatments. Arabidopsis seedlings grown on 0.05 mm Pi
      displayed shortened primary roots, higher lateral root density and reduced shoot
      biomass allocation relative to those on 0.5 mm Pi, whereas Eutrema seedlings
      showed no difference in lateral root density and shoot biomass allocation. While
      a low Fe concentration mitigated the Pi deficiency response for Arabidopsis,
      Eutrema root architecture was unaltered, but adding NaCl increased Eutrema
      lateral root density almost 2-fold. Eutrema and Arabidopsis plants grown on soil
      without added Pi for 4 weeks had low shoot and root Pi content. Pi-deprived, soil
      grown Arabidopsis plants were stunted with senescing older leaves, whereas
      Eutrema plants were visually indistinguishable from 2.5 mm Pi-supplemented
      plants. Genes associated with Pi starvation were analysed by RT-qPCR. EsIPS2,
      EsPHT1;4 and EsPAP17 showed up-regulated expression in Pi-deprived Eutrema
      plants, while EsPHR1, EsWRKY75 and EsRNS1 showed no induction. Absolute
      quantification of transcripts indicated that PHR1, WRKY75 and RNS1 were expressed
      at higher levels in Eutrema plants relative to those in Arabidopsis regardless of
      external Pi. The low phenotypic plasticity Eutrema displays to Pi supply is
      consistent with adaptation to chronic Pi deprivation in its extreme natural
      habitat.

PMID- 27038435
TI  - Histological and immunohistochemical study of estrogen and progesterone receptors
      in normal human breast tissue in adult age groups vulnerable to malignancy.
AB  - Analysis of receptor status has become standard procedure for assessing breast
      cancer patients. Estrogen causes epithelial proliferation in breast tissue via
      the estrogen receptor (ER). The progesterone receptor (PR) is also regulated by
      the estrogen gene. Analyzing ER and PR together gives information regarding the
      likely response of carcinoma patients to hormonal therapy. The aim of the present
      study was to record the expression patterns of ER and PR in normal mammary tissue
      in different age groups to provide reference data to facilitate histological
      diagnosis. Breast tissues from the upper outer quadrant of each side of 27 adult
      female cadavers were examined after H & E staining. ER and PR were identified and
      examined by immunohistochemistry. The percentage area occupied by parenchyma
      relative to stromal tissue was calculated in different age groups and was about
      4:6, 3.5:6.5, 3:7, 2:8, and 1.5:8.5 in the 3rd, 4th and 5th, 6th, 7th, 8th and
      9th, and 10th decades of life, respectively. Both ER and PR were present in all
      age groups and the numbers of both receptors were maximal during the 4th decade.
      The distribution and staining patterns for both ER and PR were recorded in
      different age groups. The contiguous pattern of ER, which is considered
      pathognomonic of breast carcinoma, was not seen except in one case in the 6th
      decade. Moderately stained ER and PR receptor sites predominated throughout. The
      study of normal breast tissue of similar age might provide comparisons that will
      help histopathologists to make clinical diagnoses from breast biopsies. Clin.
      Anat. 29:729-737, 2016. (c) 2016 Wiley Periodicals, Inc. 

PMID- 27038436
TI  - A latent profile analysis of childhood trauma in women with bulimia nervosa:
      Associations with borderline personality disorder psychopathology.
AB  - OBJECTIVE: The aim of this study was to empirically examine naturally occurring
      groups of individuals with bulimia nervosa (BN) based on their childhood trauma
      (CT) histories and to compare these groups on a clinically relevant external
      validator, borderline personality disorder (BPD) psychopathology. METHOD: This
      study examined the relationship between CT and BPD psychopathology among 133
      women with BN using latent profile analysis (LPA) to classify participants based
      on histories of CT. Participants completed the Structured Clinical Interview for
      DSM-IV Axis I Disorders (SCID-I/P), the Diagnostic Interview for Borderlines
      Revised (DIB-R), and the Childhood Trauma Questionnaire (CTQ). RESULTS: The LPA
      revealed four trauma profiles: low/no trauma, emotional trauma, sexual trauma,
      and polytrauma. Results indicated that the sexual and polytrauma profiles
      displayed significantly elevated scores on the DIB-R and that the low/no and
      emotional trauma profiles did not differ significantly on the DIB-R. Secondary
      analyses revealed elevated levels of a composite CT score among those with both
      BN and BPD psychopathology compared to those with BN only. DISCUSSION: These
      findings suggest that both childhood sexual abuse and the additive effects of
      childhood polytrauma may be linked to BPD psychopathology in BN. (c) 2016 Wiley
      Periodicals, Inc. (Int J Eat Disord 2016; 49:689-694).

PMID- 27038437
TI  - Probing the Small-Molecule Inhibition of an Anticancer Therapeutic Protein
      Protein Interaction Using a Solid-State Nanopore.
AB  - Nanopore sensing is an emerging technology for the single-molecule-based
      detection of various biomolecules. In this study, we probed the anticancer
      therapeutic p53 transactivation domain (p53TAD)/MDM2 interaction and its
      inhibition with a small-molecule MDM2 antagonist, Nutlin-3, using low-noise solid
      state nanopores. Although the translocation of positively charged MDM2 through a
      nanopore was detected at the applied negative voltage, this MDM2 translocation
      was almost completely blocked upon formation of the MDM2/GST-p53TAD complex owing
      to charge conversion. In combination with NMR data, the nanopore measurements
      showed that the addition of Nutlin-3 rescued MDM2 translocation, indicating that
      Nutlin-3 disrupted the MDM2/GST-p53TAD complex, thereby releasing MDM2. Taken
      together, our results reveal that solid-state nanopores can be a valuable
      platform for the ultrasensitive, picomole-scale screening of small-molecule drugs
      against protein-protein interaction (PPI) targets.

PMID- 27038438
TI  - Computational particle-haemodynamics analysis of liver radioembolization
      pretreatment as an actual treatment surrogate.
AB  - Liver radioembolization (RE) is a treatment option for patients with unresectable
      and chemorefractory primary and metastatic liver tumours. RE consists of intra
      arterially administering via catheter radioactive microspheres that locally
      attack the tumours, sparing healthy tissue. Prior to RE, the standard practice is
      to conduct a treatment-mimicking pretreatment assessment via the infusion of 99m
      Tc-labelled macroaggregated albumin microparticles. The usefulness of this
      pretreatment has been debated in the literature, and thus, the aim of the present
      study is to shed light on this issue by numerically simulating the liver RE
      pretreatment and actual treatment particle-haemodynamics in a patient-specific
      hepatic artery under two different literature-based cancer scenarios and two
      different placements of a realistic end-hole microcatheter in the proper hepatic
      artery. The parameters that are analysed are the following: microagent quantity
      and size (accounting for RE pretreatment and treatment), catheter-tip position
      (near the proper hepatic artery bifurcation and away from it), and cancer burden
      (10% and 30% liver involvement). The conclusion that can be reached from the
      simulations is that when it comes to mimicking RE in terms of delivering
      particles to tumour-bearing segments, the catheter-tip position is much more
      important (because of the importance of local haemodynamic pattern alteration)
      than the infused microagents (i.e. quantity and size). Cancer burden is another
      important feature because the increase in blood flow rate to tumour-bearing
      segments increases the power to drag particles. These numerical simulation-based
      conclusions are in agreement with clinically observed events reported in the
      literature. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27038439
TI  - A mini-epidemic of eruptive hypomelanosis in three children of the same family;
      the first piece of epidemiological evidence for an infectious cause of a novel
      paraviral exanthem.

PMID- 27038440
TI  - A phase I randomized trial to assess the effect on skin infiltrate thickness and
      tolerability of topical phosphodiesterase inhibitors in the treatment of
      psoriasis vulgaris using a modified psoriasis plaque test.
AB  - BACKGROUND: Oral phosphodiesterase (PDE)4 inhibitors have shown efficacy in
      chronic obstructive pulmonary disease and psoriasis. OBJECTIVES: To assess the
      effectiveness, local safety and tolerability, and systemic pharmacokinetics of
      two topical PDE4 inhibitors, roflumilast and TAK-084, in plaque psoriasis.
      METHODS: An intraindividual comparison of six topical products was made in 15
      patients aged 18-65 years with stable chronic plaque psoriasis in an investigator
      blinded, within-subject randomized study. The products evaluated were
      calcipotriol 0.005% cream; betamethasone valerate 0.1% (both in their marketed
      formulations); investigational cream formulations of roflumilast 0.5% and TAK-084
      0.5% and 5%; and a vehicle cream formulation as a control. Each treatment was
      applied daily to different test sites located on psoriasis plaques for 3 weeks.
      RESULTS: The primary end point of (mean) change from baseline in skin infiltrate
      thickness after 3 weeks of treatment showed statistically significant
      improvements for all treatments: betamethasone valerate cream (-286.9 MUm), the
      selective PDE4 inhibitors roflumilast 0.5% (-237.1 MUm) and TAK-084 (0.5% cream, 
      153.6 MUm; 5% cream, -216.7 MUm) and calcipotriol 0.005% (-187.7 MUm) when
      compared with vehicle cream control (all P < 0.001). Both the TAK-084 5% and
      roflumilast 0.5% formulations performed well overall compared with the potent
      corticosteroid, betamethasone, and were ranked better than the vitamin D analogue
      calcipotriol. All adverse events were mild or moderate and none was serious.
      CONCLUSIONS: Topical treatment with cream formulations of the PDE4 inhibitors
      roflumilast and TAK-084 reduced inflammation, measured as a change in skin
      infiltrate thickness, and reduced psoriasis severity. Corticosteroid treatments
      have known systemic and cutaneous side-effects; PDE4 inhibitors could offer an
      alternative to these and deserve further study.

PMID- 27038441
TI  - Discerning picroside-I biosynthesis via molecular dissection of in vitro shoot
      regeneration in Picrorhiza kurroa.
AB  - KEY MESSAGE: Expression analysis of primary and secondary metabolic pathways
      genes vis-a-vis shoot regeneration revealed developmental regulation of picroside
      I biosynthesis in Picrorhiza kurroa. Picroside-I (P-I) is an important iridoid
      glycoside used in several herbal formulations for treatment of various disorders.
      P-I is synthesized in shoots of Picrorhiza kurroa and Picrorhiza
      scrophulariiflora. Current study reports on understanding P-I biosynthesis in
      different morphogenetic stages, viz. plant segment (PS), callus initiation (CI),
      callus mass (CM), shoot primordia (SP), multiple shoots (MS) and fully developed
      (FD) stages of P. kurroa. Expression analysis of genes involved in primary and
      secondary metabolism revealed that genes encoding HMGR, PMK, DXPS, ISPE, GS,
      G10H, DAHPS and PAL enzymes of MVA, MEP, iridoid and shikimate/phenylpropanoid
      pathways showed significant modulation of expression in SP, MS and FD stages in
      congruence with P-I content compared to CM stage. While HK, PK, ICDH, MDH and
      G6PDH showed high expression in MS and FD stages of P. kurroa, RBA, HisK and CytO
      showed high expression with progress in regeneration of shoots. Quantitative
      expression analysis of secondary metabolism genes at two temperatures revealed
      that 7 genes HMGR, PMK, DXPS, GS, G10H, DAHPS and PAL showed high transcript
      abundance (32-87-folds) in FD stage derived from leaf and root segments at 15 
      degrees C compared to 25  degrees C in P. kurroa. Further screening of these
      genes at species level showed high expression pattern in P. kurroa (6-19-folds)
      vis-a-vis P. scrophulariiflora that was in corroboration with P-I content.
      Therefore, current study revealed developmental regulation of P-I biosynthesis in
      P. kurroa which would be useful in designing a suitable genetic intervention
      study by targeting these genes for enhancing P-I production.

PMID- 27038443
TI  - Typing of Pneumocystis jirovecii by multilocus sequencing: evidence of outbreak?
AB  - Different reports of Pneumocystis jirovecii pneumonia (PcP) outbreaks on oncology
      and transplant units suggest the possibility of a person-to-person transmission.
      Based on these reports, we searched retrospectively for possible PcP clusters in
      UZ Leuven in 2013. A movement and transmission map was established for all
      patients (n = 21) with a positive PcP PCR on BAL fluid. BAL fluid samples from
      all patients with a positive PCR on the mitochondrial large subunit mRNA of P.
      jirovecii and possible cross exposure were typed with multilocus sequence typing
      (MLST). Five patients with a positive PcP PCR could have contact with another PcP
      patient. Another five patients with a weak positive PcP PCR on BAL fluid during
      the same period were also included. Based on the MLST typing of the BAL samples
      of these ten patients, there was no evidence of a PcP outbreak in UZ Leuven in
      2013. MLST has proven to be a useful tool in genotyping and outbreak detection.
      From this case series, it could be concluded that current infection control
      precautions for P. jirovecii are appropriate in UZ Leuven. However, there is need
      for an international Pneumocystis database and more clarity in the geographic
      distribution of different P. jirovecii genotypes. 

PMID- 27038442
TI  - Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats
      Exposed Prenatally and/or Postnatally to Methamphetamine.
AB  - Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic
      abuse of which leads to neurodegenerative changes in the brain. The global use of
      MA is increasing, including in pregnant women. Since MA can cross both placental
      and haematoencephalic barriers and is also present in maternal milk, children of
      chronically abused mothers are exposed prenatally as well as postnatally. Women
      seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to
      exert its effects among others via direct interactions with dopamine transporters
      (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base
      of sex-dependent actions of MA observed in behavioural and neurochemical studies.
      Possible sex differences in the DATs of preadolescent offspring exposed to MA
      prenatally and/or postnatally have not yet been evaluated. We examined the
      striatal synaptosomal DATs (the activity and density of surface expressed DATs
      and total DAT expression) in preadolescent male and female Wistar rats (31-35-day
      old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to
      mothers during pregnancy and lactation). To distinguish between specific and
      nonspecific effects of MA on DATs, we also evaluated the in vitro effects of
      lipophilic MA on the fluidity of striatal membranes isolated from preadolescent
      and young adult rats of both sexes. We observed similar changes in the DATs of
      preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the
      reserve pool but no alterations in surface-expressed DATs). However, prenatal
      exposure evoked significant changes in males and postnatal exposure in females. A
      significant decrease in the activity of surface-expressed DATs was found only in
      postnatally exposed females sensitized to MA via prenatal exposure. MA applied in
      vitro increased the fluidity of striatal membranes of preadolescent female but
      not male rats. In summary, DATs of preadolescent males are more sensitive to
      prenatal MA exposure via changes in the reserve pool and those of preadolescent
      females to postnatal MA exposure via the same mechanism. The combination of
      prenatal and postnatal MA exposure increases the risk of dopaminergic deficits
      via alterations in the activity of surface-expressed DATs especially in
      preadolescent females. MA-mediated changes in DATs of preadolescent females could
      be still enhanced via nonspecific disordering actions of MA on striatal
      membranes. 

PMID- 27038444
TI  - Clinical Significance of Serum Galectin-3 Levels in Gastric Cancer Patients.
AB  - PURPOSE: Galectin-3, a member of the galectin family, is an endogenous beta
      galactoside-binding lectin. It plays an important role in the pathogenesis of
      multiple malignancies and its expression strongly also affects the outcomes of
      cancer patients. The objective of this study was to determine the clinical
      significance of the serum levels of galectin-3 in gastric cancer patients.
      MATERIAL AND METHODS: A total of 58 patients with diagnosis of gastric cancer
      were enrolled into this study. Serum galectin-3 concentrations were determined by
      the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls
      were included in the analysis. RESULTS: The median age at diagnosis was 59.5
      years, range 32 to 82 years. There was no significant difference in the baseline
      serum galectin-3 levels between gastric cancer patients and healthy controls (p =
      0.357). The older patients had elevated galectin-3 levels compared with younger
      ones (p = 0.02). The other known clinical variables including gender, site of
      lesion, histopathology, tumor size, lymph node involvement, and stage of disease
      were not correlated with serum galectin-3 concentrations (p > 0.05). Moreover, no
      relationship was shown between serum galectin-3 level and chemotherapy
      responsiveness (p = 0.36). Likewise, serum galectin-3 concentrations were not
      associated with prognosis on survival (p = 0.54). CONCLUSION: Serum levels of
      galectin-3 have no diagnostic, predictive and prognostic roles in gastric cancer
      patients.

PMID- 27038445
TI  - Does remifentanil improve ECT seizure quality?
AB  - Studies have reported that co-adjuvant remifentanil can enhance electroconvulsive
      therapy (ECT) seizure quality, putatively by allowing a reduction in the dosage
      of the main anaesthetic agents, as the latter have anticonvulsant properties.
      However, whether remifentanil also has direct effects on ECT seizure quality, and
      by implication, treatment efficacy, is unknown. This is the first study examining
      the effect of adjuvant remifentanil on ECT seizure quality when the dose of
      conventional anaesthesia remained unchanged. A total of 96 ECT sessions (from 36
      patients) were retrospectively analysed. Subjects received ECT with and without
      remifentanil (1 ug/kg), while the dose of thiopentone (3-5 mg/kg) or propofol (1
      2 mg/kg) was unchanged. Seizure quality indices (time to slow wave activity or
      TSLOW, amplitude, regularity, stereotypy, post-ictal suppression) and duration
      were assessed through a structured rating scale by a single trained blinded
      rater. Linear mixed-effects models with random subject effects analysed the
      effect of remifentanil on seizure parameters, controlling for other variables
      that can affect seizure quality or duration. Remifentanil was given in 47.9 % of
      the ECT sessions. Co-adjuvant remifentanil had no effects on any of the seizure
      quality parameters analysed [TSLOW (E = -0.21, p > 0.1), amplitude (E = 0.08, p >
      0.5), regularity (E = -0.05, p > 0.5), stereotypy (E = -0.02, p > 0.5),
      suppression (E = -0.3, p > 0.05)] or on seizure duration (E = -0.25, p > 0.1).
      While adjuvant remifentanil may be a useful strategy for reducing anaesthetic
      dosage in ECT, present evidence suggests that remifentanil does not have
      intrinsic properties that enhance ECT seizures.

PMID- 27038446
TI  - Diagnosis and Surveillance of Barrett's Esophagus: Addressing the Transatlantic
      Divide.
AB  - BACKGROUND: Barrett's esophagus is a premalignant condition of the esophagus
      leading to esophageal adenocarcinoma. No consensus exists between the UK and USA
      concerning the diagnosis of Barrett's esophagus. Although the diagnostic
      procedure is common, the required findings and diagnostic criteria vary. Both
      guidelines require endoscopy showing columnar epithelia lining the esophagus, but
      the US guidelines require the additional finding of intestinal metaplasia on
      biopsy to confirm diagnosis. Achievement of a consensus is of particular
      importance due to the established progression from Barrett's esophagus to
      esophageal adenocarcinoma. Of further importance is the increasing incidence of
      esophageal adenocarcinoma, a condition with poor overall survival, leading to
      various opinions on the utility of surveillance in patients. DISCUSSION: A review
      of the vast array of literature revealed that substantial evidence exists in
      favor of both diagnostic criteria; hence, there is no easy way to identify the
      "correct" method of diagnosing Barrett's esophagus. USA recommends surveillance
      of Barrett's esophagus, whereas UK does not advocate it unless dysplasia is
      present. Surveillance was found to be effective, but this varied as did cost
      effectiveness. Further research into diagnostic methods for Barrett's esophagus
      is needed to address areas of limited understanding, such that agreement can be
      reached and practice standardized. Surveillance was generally advocated, but with
      different criteria and time intervals, and new methods are being evaluated.

PMID- 27038447
TI  - Spontaneous Regression of Hepatocellular Carcinoma with Multiple Lung Metastases:
      A Case Report and Review of the Literature.
AB  - Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event. Here we
      present a case of spontaneous regression of metastatic HCC. A 53-year-old man
      with hepatitis C and alcoholic cirrhosis was found to have a large liver mass
      consistent with HCC based on its radiographic features. Imaging also revealed
      left portal and hepatic vein thrombosis, as well as multiple lung nodules
      concerning for metastases. Approximately 2 months after the initial diagnosis,
      both the primary liver lesion and the lung metastases decreased in size and
      eventually resolved without any intervention. Thereafter, the left hepatic vein
      thrombus progressed into the inferior vena cava and the right atrium, and the
      patient died due to right heart failure. In this case report and literature
      review, we discuss the potential mechanisms for and review the literature on
      spontaneous regression of metastatic HCC.

PMID- 27038449
TI  - Minimally invasive anterior chest wall lifting technique for thoracoscopic
      mediastinal approach.
AB  - Anterior chest wall lifting facilitates a wide view and allows easy access during
      thoracoscopic surgery in a supine position for anterior mediastinal lesions. We
      previously reported an anterior chest wall lifting method for a thymectomy that
      utilizes our original costal hooks. Here, we present a less invasive method that
      can be performed with only a needle puncture, i.e., a metal plate placed under
      the ribs is lifted with a wire inserted through the anterior chest wall. We have
      applied this novel 'T-lifting method' for 5 different cases with anterior
      mediastinal tumors, and found it to be simple and easy to perform, as well as
      less invasive for patients undergoing thoracoscopic surgery.

PMID- 27038450
TI  - Protein corona: The golden gate to clinical applications of nanoparticles.

PMID- 27038448
TI  - Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US
      Minority Populations.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome
      predicted to be the next global epidemic affecting millions of people worldwide.
      The natural course of this disease including its subtype, non-alcoholic
      steatohepatitis (NASH), is not clearly defined especially in the African-American
      segment of the US population. AIMS: To conduct a review of the global
      epidemiology of NAFLD with emphasis on US minority populations. METHODS: A
      thorough search of evidence-based literature was conducted using the Pubmed
      database and commercial web sources such as Medscape and Google Scholar. RESULTS:
      NAFLD and its subtype NASH are becoming the principal cause of chronic liver
      disease across the world. In the US, Hispanics are the most disproportionately
      affected ethnic group with hepatic steatosis, and elevated aminotransferase
      levels, whereas African-Americans are the least affected. Genetic disparities
      involved in lipid metabolism seem to be the leading explanation for the lowest
      incidence and prevalence of both NAFLD and NASH in African-Americans.
      CONCLUSIONS: The unprecedented rise in the prevalence of NAFLD globally requires
      an initiation of population cohort studies with long-term follow-up to determine
      the incidence and natural history of NAFLD and its underrepresentation in African
      Americans. Future studies should also focus on the delineation of the interplay
      between genetic and environmental factors that trigger the development of NAFLD
      and NASH.

PMID- 27038452
TI  - Modeling Learning in Doubly Multilevel Binary Longitudinal Data Using Generalized
      Linear Mixed Models: An Application to Measuring and Explaining Word Learning.
AB  - When word learning is supported by instruction in experimental studies for
      adolescents, word knowledge outcomes tend to be collected from complex data
      structure, such as multiple aspects of word knowledge, multilevel reader data,
      multilevel item data, longitudinal design, and multiple groups. This study
      illustrates how generalized linear mixed models can be used to measure and
      explain word learning for data having such complexity. Results from this
      application provide deeper understanding of word knowledge than could be attained
      from simpler models and show that word knowledge is multidimensional and depends
      on word characteristics and instructional contexts.

PMID- 27038451
TI  - Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2
      diabetes patients: a randomised, double-blind, placebo-controlled trial.
AB  - AIMS/HYPOTHESIS: This study aimed to investigate the acute renal effects of the
      glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes
      patients. METHODS: We included overweight (BMI 25-40 kg/m(2)) men and
      postmenopausal women, aged 35-75 years with type 2 diabetes (HbA1c 48-75
      mmol/mol; 6.5-9.0%) and estimated GFR >= 60 ml min(-1) 1.73 m(-2). Exenatide or
      placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute,
      randomised, double-blind, placebo-controlled trial conducted at the Diabetes
      Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective
      renal plasma flow (ERPF) were determined by inulin and para-aminohippurate
      clearance, respectively, based on timed urine sampling. Filtration fraction (FF)
      and effective renal vascular resistance (ERVR) were calculated, and glomerular
      hydrostatic pressure (PGLO) and vascular resistance of the afferent (RA) and
      efferent (RE) renal arteriole were estimated. Tubular function was assessed by
      absolute and fractional excretion of sodium (FENa), potassium (FEK) and urea
      (FEU), in addition to urine osmolality, pH and free water clearance. Renal damage
      markers, BP and plasma glucose were also determined. RESULTS: Of the 57 patients
      randomised by computer, 52 were included in the final analyses. Exenatide (n =
      24) did not affect GFR (mean difference +2 +/- 3 ml min(-1) 1.73 m(-2), p =
      0.489), ERPF, FF, ERVR or PGLO, compared with placebo (n = 28). Exenatide
      increased RA (p < 0.05), but did not change RE. Exenatide increased FENa, FEK,
      urine osmolality and pH, while FEU, urinary flow and free water clearance were
      decreased (all p < 0.05). Osmolar clearance and renal damage makers were not
      affected. Diastolic BP and mean arterial pressure increased by 3 +/- 1 and 6 +/-
      2 mmHg, respectively, whereas plasma glucose decreased by 1.4 +/- 0.1 mmol/l (all
      p < 0.05). CONCLUSIONS/INTERPRETATION: Exenatide infusion does not acutely affect
      renal haemodynamics in overweight type 2 diabetes patients at normal filtration
      levels. Furthermore, acute GLP-1RA administration increases proximal sodium
      excretion in these patients. TRIAL REGISTRATION: ClincialTrials.gov NCT01744236
      FUNDING : The research leading to these results has been funded from: (1) the
      European Community's Seventh Framework Programme (FP7/2007-2013) under grant
      agreement number 282521 - the SAFEGUARD project; and (2) the Dutch Kidney
      Foundation, under grant agreement IP12.87.

PMID- 27038453
TI  - Good news about the ESNR-Springer Award.

PMID- 27038454
TI  - Bovine viral diarrhea virus structural protein E2 as a complement regulatory
      protein.
AB  - Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, family
      Flaviviridae, and is one of the most widely distributed viruses in cattle
      worldwide. Approximately 60 % of cattle in endemic areas without control measures
      are infected with BVDV during their lifetime. This wide prevalence of BVDV in
      cattle populations results in significant economic losses. BVDV is capable of
      establishing persistent infections in its host due to its ability to infect
      fetuses, causing immune tolerance. However, this cannot explain how the virus
      evades the innate immune system. The objective of the present work was to test
      the potential activity of E2 as a complement regulatory protein. E2 glycoprotein,
      produced both in soluble and transmembrane forms in stable CHO-K1 cell lines, was
      able to reduce complement-mediated cell lysis up to 40 % and complement-mediated
      DNA fragmentation by 50 %, in comparison with cell lines not expressing the
      glycoprotein. This work provides the first evidence of E2 as a complement
      regulatory protein and, thus, the finding of a mechanism of immune evasion by
      BVDV. Furthermore, it is postulated that E2 acts as a self-associated molecular
      pattern (SAMP), enabling the virus to avoid being targeted by the immune system
      and to be recognized as self. 

PMID- 27038455
TI  - Chronic idiopathic normocytic anaemia in older people: the risk factors and the
      role of age-associated renal impairment.
AB  - OBJECTIVES: To characterise the risk factors for chronic idiopathic normocytic
      anaemia (CINA) in older people, particularly the role of age-associated renal
      impairment. METHODS: Patients aged >=65 years admitted to a medical unit over 12
      months were assessed. Those with secondary causes of anaemia including chronic
      kidney disease (CKD) were excluded. CINA was defined as a haemoglobin <130 g/l
      for men and <120 g/l for women for at least 6 months without any apparent cause.
      Renal function was determined by estimating creatinine clearance (CrCl) using
      Cockcroft-Gault formula, and glomerular filtration rate (GFR) using modification
      of diet in renal disease (MDRD) and chronic kidney disease epidemiology
      collaboration (CKD-EPI) formulas. RESULTS: 116 had CINA. Controls were 572. The
      mean estimates of renal function were significantly lower in cases as compared
      with controls (P < 0.001). The risk of CINA increased by 12.6, 10.4 and 12 %,
      respectively, for each unit decrease in CrCl, MDRD-eGFR and CKD-EPI-eGFR,
      independent of age and other covariates. The adjusted odds ratios for CINA in
      those with CrCl, MDRD or CKD-EPI eGFR <60 ml/min/1.73 m2 were 2.68 (CI 1.53
      4.70); 2.70 (CI 1.57-4.62) and 2.12 (CI 1.46-3.74), respectively. Other
      covariates in the model that were independently associated with CINA included
      advanced age, diabetes mellitus (DM), use of angiotensin converting enzyme
      inhibitor (ACEI) or angiotensin receptor blocker (ARB), history of dementia and
      living in a residential care facility. CONCLUSIONS: Age-associated renal
      impairment independently contributes to CINA. Other potential risk factors for
      CINA include advanced age, DM and ACEI or ARB use.

PMID- 27038457
TI  - Laparoscopic Pancreaticoduodenectomy with Reconstruction of the Portal Vein with
      the Parietal Peritoneum.
AB  - INTRODUCTION: Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used for
      resections of periampullary tumors, including pancreatic adenocarcinoma.1 LPD
      with venous resection-reconstruction (VRR) has already been performed with or
      without vascular graft.2 (,) 3 The parietal peritoneum (PP) was recently
      described for reconstruction of the mesenterico-portal vein, with excellent
      results.4 PATIENTS AND METHODS: Between April 2011 and May 2015, a total of 64
      LPDs were performed in our department; however, only one patient underwent VRR.
      Compared with the open approach, full mobilization of the mesentery and right
      liver is not systematically carried out and, theoretically, vascular grafts may
      be more frequently needed with LPD. In this video, LPD for pancreatic
      adenocarcinoma with resection of the lateral right side of the portal vein (>25
      mm) was performed. Reconstruction was achieved rapidly, as a lateral patch, with
      the falciform ligament. RESULTS: Surgery lasted 360 min, 60 min of portal vein
      occlusion, 200 ml of blood loss, and uneventful stay. Since 2010, the PP has been
      used as a lateral patch in 69 patients operated by open (n = 68) or laparoscopic
      approach (n = 1). Although handling and suturing can be difficult, no bleeding
      complications related to the PP were observed and the permeability rate was >95
      %. CONCLUSION: LPD is still restricted to selected centers, with conflicting
      results regarding safety; however, venous resection may be required. We feel that
      with the laparoscopic approach, vascular grafts are more frequently needed and
      the PP has many advantages compared with an open approach, including easy access,
      unlimited size, and rapid harvesting.

PMID- 27038456
TI  - A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric
      Micelles.
AB  - Curcumin, a phenolic compound, possesses many pharmacological activities and is
      under clinical evaluation to treat different diseases. However, conflicting data
      about its stability have been reported. In this study, the kinetic degradation of
      curcumin from a natural curcuminoid mixture under various conditions (pH,
      temperature, and dielectric constant of the medium) was investigated. Moreover,
      the degradation of pure curcumin at some selected conditions was also determined.
      To fully solubilize curcumin and to prevent precipitation of curcumin that occurs
      when low concentrations of co-solvent are present, a 50:50 (v/v) aqueous
      buffer/methanol mixture was used as standard medium to study its degradation
      kinetics. The results showed that degradation of curcumin both as pure compound
      and present in the curcuminoid mixture followed first order kinetic reaction. It
      was further shown that an increasing pH, temperature, and dielectric constant of
      the medium resulted in an increase in the degradation rate. Curcumin showed rapid
      degradation due to autoxidation in aqueous buffer pH = 8.0 with a rate constant
      of 280 * 10(-3) h(-1), corresponding with a half-life (t1/2) of 2.5 h.
      Dioxygenated bicyclopentadione was identified as the final degradation product.
      Importantly, curcumin loaded as curcuminoid mixture in omega-methoxy poly
      (ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (mPEG-HPMA-Bz)
      polymeric micelles and in Triton X-100 micelles was about 300-500 times more
      stable than in aqueous buffer. Therefore, loading of curcumin into polymeric
      micelles is a promising approach to stabilize this compound and develop
      formulations suitable for further pharmaceutical and clinical studies.

PMID- 27038458
TI  - Protecting Nipple Perfusion by Devascularization and Surgical Delay in Patients
      at Risk for Ischemic Complications During Nipple-Sparing Mastectomies.
AB  - BACKGROUND: Indications for nipple-sparing mastectomy (NSM) are expanding;
      however, high-risk patients have more ischemic complications. Surgical
      devascularization of the nipple-areolar complex (NAC) prior to NSM can reduce
      complications. This study reports perfusion patterns and complications in high
      risk patients undergoing 2-stage NSM. METHODS: Surgical devascularization of the
      NAC was performed 3-6 weeks prior to NSM in 28 women. Risk factors included
      ptosis, obesity, smoking, prior breast surgery, and radiation. Using indocyanine
      green (ICG)-based fluorescence and an infrared camera, blood inflow was
      visualized intraoperatively. NAC perfusion patterns were classified as: V1,
      underlying breast; V2, surrounding skin; V3 = V1 + V2, or V4, capillary fill
      following devascularization. Ischemic complications were analyzed. RESULTS:
      Baseline perfusion for 54 breasts was 35 % V1, 32 % V2, and 33 % V3. Increasing
      ptosis was associated with V1 pattern: 86 % for grade 3, 31 % for grade 2, and 18
      % for grade 1. Postdevascularization epidermolysis was observed in 63 % of V1
      baseline, 41 % of V2, and 22 % of V3 (P = .042) and after NSM in 26 % for V1, 7 %
      for V2, and 6 % for V3 (P = .131). Ptosis was significantly associated with
      epidermolysis postdevascularization (P = .002) and NSM (P = .002). Smoking and
      BMI >=30 were related to increased ischemic complications. Two or more risk
      factors were associated with postdevascularization ischemic changes (P = .026),
      but were not significant after NSM. Nipple loss was not observed, but 2 patients
      underwent partial areolar resection. CONCLUSION: Adaptive circulatory changes
      after devascularization allow tissues to tolerate the additional ischemic
      challenge of mastectomy. Our findings support extending 2-staged operations to
      high-risk women previously considered unsuitable for NSM.

PMID- 27038459
TI  - Fighting Global Disparities in Cancer Care: A Surgical Oncology View.
AB  - Cancer is the second leading cause of death globally after cardiovascular
      disease. Long-term cancer survival has improved in the Western world due to early
      detection and the use of effective combined treatment modalities, as well as the
      development of effective immunotherapy and drug-targeted therapy. Surgery is
      still the mainstay for most solid tumors; however, low- and middle-income
      countries are facing an increasing lack of primary surgical care for easily
      treatable conditions, including breast, colon, and head and neck cancers. In this
      paper, a surgical oncology view is presented to elaborate how the Western
      surgical oncologist can take part in the 'surgical fight' against global
      disparities in cancer care, and a plea is made to strive for structural
      solutions, such as a partnership in surgical oncology training. The pros and cons
      of the use of eHealth and mHealth technologies and education programs for schools
      and the community are discussed as these create an opportunity to reach a large
      portion of the population in these countries, at low cost and with high impact.

PMID- 27038460
TI  - Mouse Models for Immune-Mediated Platelet Destruction or Immune Thrombocytopenia
      (ITP).
AB  - Immune thrombocytopenia (ITP) is a debilitating, life-threatening autoimmune
      disorder affecting more than 4 in every 100,000 adults annually, stemming from
      the production of antiplatelet antibody resulting in accelerated platelet
      destruction and thrombocytopenia. Numerous animal models of ITP have been
      developed that contributed to the basic understanding of the underlying
      mechanisms of ITP onset, progression, and maintenance. Rodent models that develop
      ITP spontaneously, or by passive transfer of an antiplatelet sera or antibody,
      play an instrumental role in the investigation of ITP mechanisms responsible for
      the breakdown of tolerance in human ITP, in studies of the immunopathology
      underlying the progression of platelet destruction, and in elucidation of the
      mechanisms of therapeutic amelioration of ITP by existing and new therapeutic
      modalities. This unit captures the protocols for the implementation and readout
      of passive antibody transfer mouse models of ITP, established by the infusion of
      a commercially-available monoclonal rat anti-mouse CD41 platelet antibody.

PMID- 27038461
TI  - Measuring Bioenergetics in T Cells Using a Seahorse Extracellular Flux Analyzer.
AB  - This unit contains several protocols to determine the energy utilization of T
      cells in real-time using a Seahorse Extracellular Flux Analyzer
      (http://www.seahorsebio.com). The advantages to using this machine over
      traditional metabolic assays include the simultaneous measurement of glycolysis
      and mitochondrial respiration, in real-time, on relatively small numbers of
      cells, without any radioactivity. The Basic Protocol describes a standard
      mitochondrial stress test on the XF(e) 96, which yields information about
      oxidative phosphorylation and glycolysis, two energy-generating pathways. The
      alternate protocols provide examples of adaptations to the Basic Protocol,
      including adjustments for the use of the XF(e) 24. A protocol for real-time
      bioenergetic responses to T cell activation allows for the analysis of immediate
      metabolic changes after T cell receptor stimulation. Specific substrate
      utilization can be determined by the use of differential assay media, or the
      injection of drugs that specifically affect certain metabolic processes. Accurate
      cell numbers, purity, and viability are critical to obtain reliable results.

PMID- 27038463
TI  - In Vivo Depletion of T Lymphocytes.
AB  - In vivo depletion of T lymphocytes is a means of studying the role of specific T
      cell populations during defined phases of in vivo immune responses. In this unit,
      a protocol is provided for injecting monoclonal antibodies (mAbs) into wild-type
      adult mice. Depletion of the appropriate subset of cells is verified by flow
      cytometry analysis of lymph node and spleen cell suspensions in pilot
      experiments. Once conditions have been established, depleted mice can be used to
      study the impact of T cell subsets on a variety of in vivo immune responses. The
      depleted condition may be maintained by repeated injections of the monoclonal
      antibody, or reversed by normal thymopoiesis following discontinuation of
      antibody administration.

PMID- 27038462
TI  - Differentiation and Characterization of Tr1 Cells.
AB  - Regulatory T cell-mediated suppression serves as a pivotal mechanism of negative
      regulation of immune-mediated inflammation. Type 1 regulatory T cells (Tr1 cells)
      are an important subset of CD4+ T cells that prevent excessive inflammatory
      responses and maintain immune tolerance. The anti-inflammatory role of Tr1 cells
      is mediated in part by their production of interleukin 10 (IL-10), which dampens
      the function of both antigen-presenting cells and antigen-specific effector T
      cells. Additionally, Tr1 cells can kill effector and myeloid cells through the
      perforin-granzyme B pathway. Adoptive transfer of in vitro differentiated Tr1
      cells can be used to suppress autoimmune tissue inflammation in vivo. This unit
      describes the in vitro stimulation of naive murine CD4+ T cells using IL-27 to
      generate IL-10-producing Tr1 cells.

PMID- 27038464
TI  - Contact Hypersensitivity.
AB  - Contact hypersensitivity (CHS) is a simple in vivo assay of cell-mediated immune
      function in which exposure of epidermal and dermal cells to exogenous haptens
      results in a delayed-type hypersensitivity (DTH) reaction that can be measured
      and quantified. Epidermal Langerhans cells and dermal dendritic cells are the
      critical antigen-presenting cells in this reaction which initiate sensitization
      to haptens by presenting antigens to CD4- and CD8-bearing T lymphocytes which, in
      turn, secrete cytokines and recruit other cells to the site of the reaction. In
      the protocol described here, mice are shaved and the skin of their abdomens is
      exposed to a hapten. After 5 or 6 days (the afferent phase), the baseline ear
      thickness is measured prior to initiation of the efferent phase. Finally, the ear
      is treated epicutaneously with the hapten solution and ear thickness is measured
      in ~24 hr. The magnitude of the ear swelling reaction after allergen treatment
      reflects the strength of the immune response.

PMID- 27038465
TI  - The Associations and Correlations Between Self-reported Health and Neighborhood
      Cohesion and Disorder in a Community-dwelling U.S. Chinese Population.
AB  - Purpose of the Study: Characteristics of neighborhood have been found to be
      associated with physical and psychological health status of older adults,
      especially in relationship to social dynamics like cohesion and disorder. This
      study aims to examine correlations and associations between sociodemographic
      characteristics, self-reported health status, cohesion, and disorder among
      Chinese older adults in the greater Chicago area. Design and Methods: The
      Population Study of Chinese Elderly in Chicago is a cross-sectional, population
      based study with community-dwelling Chinese older adults aged 60 and older,
      recruited through a community-based participatory research approach. Cohesion was
      measured through six questions; disorder was measured through eight questions.
      Correlation and regression analyses were conducted using SAS. Results: Among
      3,158 participants enrolled in the study, 92.3% reported any neighborhood
      cohesion; 69.8% reported any neighborhood disorder. After controlling for age,
      sex, education, income, marital status, living arrangement, number of children,
      years in the community, years in the United States, country of origin, language
      preference, and location, a higher level of cohesion is associated with higher
      quality of life (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.13, 1.39)
      and a higher level of disorder is associated with lower overall health status
      (OR: 0.97, 95% CI: 0.95, 0.99) and lower quality of life (OR: 0.96, 95% CI: 0.95,
      0.98). Implications: Our findings suggest that neighborhood cohesion and
      neighborhood disorder are correlated to the health of U.S. Chinese older adults.
      Future longitudinal research should examine the relationship between community
      characteristics, both structural and social, and health-related outcomes.

PMID- 27038466
TI  - Diabetes-induced perturbations are subject to intergenerational transmission
      through maternal line.
AB  - The hypothesis of fetal origins of adult disease states that early life events
      program the occurrence of significant adult diseases, including diabetes and
      obesity. Maternal diabetes is associated with general stress environment for
      developing fetus, and gestational diabetes is an independent risk factor for type
      2 diabetes and metabolic syndrome in offspring. Intra-uterine fetal programming
      of fetal tissues exposes the offspring to increased risk of impaired glucose
      tolerance, type 2 diabetes, and cardiovascular disease. Here, we examined the
      transmission of maternal diabetes-induced fetal programming in second generation
      and compared maternal and paternal routes of intergenerational effects. We
      organized 40 Wistar rats into three groups, male offspring of diabetic mothers,
      female offspring of diabetic mothers, and offspring of control mothers. These
      groups were mated with normal healthy rats to assess the effect of grand-maternal
      diabetes on pregnancy outcome in F2 rats, as well as glucose-sensing parameters,
      insulin resistance, and glucose tolerance prenatally and postnatally. We found
      that F2 offspring of diabetic mothers had impaired glucose sensing, increased
      oxidative stress, insulin resistance, and impaired glucose tolerance, and these
      effects were more prominent in the F2 offspring of F1 female rats (F2-DF1F). We
      deduce that fetal programming of maternal diabetes is mostly transmitted through
      maternal line across two generations. 

PMID- 27038467
TI  - The Effects of Pop-up Harm Minimisation Messages on Electronic Gaming Machine
      Gambling Behaviour in New Zealand.
AB  - In New Zealand a simple pop-up message feature that provides gambling session
      information and forces a break in play is mandatory on all electronic gaming
      machines in all venues (EGMs). Previous research has demonstrated small effects
      of more sophisticated pop-up messages tested predominantly in laboratory
      environments. The present research examined gambler engagement with and views on
      the New Zealand pop-up messages and on the relationship between pop-up messages
      and EGM expenditure. A sample of gamblers was recruited at casino and non-casino
      (pub) EGM venues. Most participants were aware of pop-up messages (57 %) and many
      saw them often (38 %). Among gamblers who reported seeing pop-up messages, half
      read the message content, and a quarter believed that pop-up messages helped them
      control the amount of money they spend on gambling. Participants who reported
      being likely to stop gambling in response to pop-up messages spent significantly
      less money on gambling when variables that were independently associated with EGM
      expenditure were controlled for. A modest harm minimisation effect of the pop-up
      message feature that has been operating in New Zealand for 5 years was evident.
      Suggestions for improvement of the harm minimisation potential of the current pop
      up message feature are discussed.

PMID- 27038468
TI  - Age of Onset and Lifetime Projected Risk of Psychotic Experiences: Cross-National
      Data From the World Mental Health Survey.
AB  - BACKGROUND: Given the early age of onset (AOO) of psychotic disorders, it has
      been assumed that psychotic experiences (PEs) would have a similar early AOO. The
      aims of this study were to describe (a) the AOO distribution of PEs, (b) the
      projected lifetime risk of PEs, and (c) the associations of PE AOO with selected
      PE features. METHODS: Data came from the WHO World Mental Health (WMH) surveys. A
      total of 31 261 adult respondents across 18 countries were assessed for lifetime
      prevalence of PE. Projected lifetime risk (at age 75 years) was estimated using a
      2-part actuarial method. AOO distributions were described for the observed and
      projected estimates. We examined associations of AOO with PE type metric and
      annualized PE frequency. RESULTS: Projected lifetime risk for PEs was 7.8% (SE =
      0.3), slightly higher than lifetime prevalence (5.8%, SE = 0.2). The median
      (interquartile range; IQR) AOO based on projected lifetime estimates was 26 (17
      41) years, indicating that PEs commence across a wide age range. The AOO
      distributions for PEs did not differ by sex. Early AOO was positively associated
      with number of PE types (F = 14.1, P < .001) but negatively associated with
      annualized PE frequency rates (F = 8.0, P < .001). DISCUSSION: While most people
      with lifetime PEs have first onsets in adolescence or young adulthood, projected
      estimates indicate that nearly a quarter of first onsets occur after age 40
      years. The extent to which late onset PEs are associated with (a) late onset
      mental disorders or (b) declining cognitive and/or sensory function need further
      research.

PMID- 27038469
TI  - Environmental Social Stress, Paranoia and Psychosis Liability: A Virtual Reality
      Study.
AB  - The impact of social environments on mental states is difficult to assess,
      limiting the understanding of which aspects of the social environment contribute
      to the onset of psychotic symptoms and how individual characteristics moderate
      this outcome. This study aimed to test sensitivity to environmental social stress
      as a mechanism of psychosis using Virtual Reality (VR) experiments. Fifty-five
      patients with recent onset psychotic disorder, 20 patients at ultra high risk for
      psychosis, 42 siblings of patients with psychosis, and 53 controls walked 5 times
      in a virtual bar with different levels of environmental social stress. Virtual
      social stressors were population density, ethnic density and hostility. Paranoia
      about virtual humans and subjective distress in response to virtual social stress
      exposures were measured with State Social Paranoia Scale (SSPS) and self-rated
      momentary subjective distress (SUD), respectively. Pre-existing (subclinical)
      symptoms were assessed with the Community Assessment of Psychic Experiences
      (CAPE), Green Paranoid Thoughts Scale (GPTS) and the Social Interaction Anxiety
      Scale (SIAS). Paranoia and subjective distress increased with degree of social
      stress in the environment. Psychosis liability and pre-existing symptoms, in
      particular negative affect, positively impacted the level of paranoia and
      distress in response to social stress. These results provide experimental
      evidence that heightened sensitivity to environmental social stress may play an
      important role in the onset and course of psychosis.

PMID- 27038470
TI  - Proton Gradients as a Key Physical Factor in the Evolution of the Forced
      Transport Mechanism Across the Lipid Membrane.
AB  - A critical phase in the transition from prebiotic chemistry to biological
      evolution was apparently an asymmetric ion flow across the lipid membrane. Due to
      imbalance in the ion flow, the early lipid vesicles could selectively take the
      necessary molecules from the environment, and release the side-products from the
      vesicle. Natural proton gradients played a definitively crucial role in this
      process, since they remain the basis of energy transfer in the present-day cells.
      On the basis of this supposition, and the premise of the early vesicle membrane's
      impermeability to protons, we have shown that the emergence of the proton
      gradient in the lipid vesicle could be a key physical factor in the evolution of
      the forced transport mechanism (pore formation and active transport) across the
      lipid bilayer. This driven flow of protons across the membrane is the result of
      the electrochemical proton gradient and osmotic pressures on the integrity of the
      lipid vesicle. At a critical number of new lipid molecules incorporated into the
      vesicle, the energies associated with the creation of the proton gradient exceed
      the bending stiffness of the lipid membrane, and overlap the free energy of the
      lipid bilayer pore formation.

PMID- 27038471
TI  - In silico transcriptional regulation and functional analysis of dengue shock
      syndrome associated SNPs in PLCE1 and MICB genes.
AB  - Single nucleotide polymorphisms (SNPs) in PLCE1 and MICB genes increase risk for
      the development of dengue shock syndrome (DSS). We used Bioinformatics tools to
      predict alterations at the transcriptional and posttranslational levels driven by
      PLCE1 and MICB SNPs associated with DSS. Functional and phenotypic analysis
      conducted to determine deleterious SNPs and impact of amino acid substitution on
      the structure and function of proteins identified rs2274223 (H1619R) as
      deleterious to protein coding as it induces structural change in the C2 domain of
      PLCepsilon, with the mutant residue more positively charged than the wild-type
      residue (RMSD score, 1.75 A). Moreover, rs2274223 condenses the chromatin
      repressing PLCepsilon expression in DSS. Briefly, this study presents the impact
      of a single nucleotide transition at SNPs associated with DSS on differential
      protein binding patterns with PLCE1 and MICB genes and on protein structure
      modification and their possible role in the pathogenesis of DSS. 

PMID- 27038472
TI  - Hypoxia regulates stemness of breast cancer MDA-MB-231 cells.
AB  - Human breast cancers include cancer stem cell populations as well as non
      tumorigenic cancer cells. Breast cancer stem cells possess self-renewal
      capability and thus are the root cause of recurrence and metastasis of malignant
      tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and
      exerts a wide range of effects on the biological behavior of cancer cells.
      However, there is little information on the role of hypoxia in modulating the
      stemness of breast cancer cells. In the present study, we cultured MDA-MB-231
      cells in a hypoxic gas mixture to simulate the hypoxic environment in tissues and
      to determine how hypoxia conditions could affect the cell proliferation,
      apoptosis, cytotoxicity, and colony-forming ability. Expression of the stem cell
      phenotype CD24(-)CD44(+)ESA(+) was analyzed to assess the effects of hypoxia on
      stemness transformation in MDA-MB-231 cells. Our results found that the cell
      toxicity of MDA-MB-231 cells was not affected by hypoxia. Hypoxia could slightly
      inhibit the growth of MDA-MB-231 cells, but the inhibitory effect is not
      significant when compared with normoxic control. Moreover, hypoxia significantly
      blocked the apoptosis in MDA-MB-231 cells (P < 0.05). The proportion of CD24(
      )CD44(+)ESA(+) cells in MDA-MB-231 cells was increased greatly after they were
      treated with hypoxia, and cell colony-formation rate of MDA-MB-231 cells also
      increased significantly in hypoxia-treated cells. These results encourage the
      exploration of hypoxia as a mechanism which might not be underestimated in chemo
      resistant breast cancer treatment. 

PMID- 27038473
TI  - Multi-kinase inhibitors, AURKs and cancer.
AB  - Inhibitors that impact function of kinases are valuable both for the biological
      research as well as therapy of kinase-associated diseases, such as different
      cancers. There are quite a number of inhibitors, which are quite specific for
      certain kinases and several of them are either already approved for the cancer
      therapy or are in clinical studies of various phases. However, that does not mean
      that each single kinase inhibitor is suitable for targeted therapy. Some of them
      are not effective others might be toxic or fail some other criteria for the use
      in vivo. On the other hand, even in case of successful therapy, many responders
      eventually develop resistance to the inhibitors. The limitations of various
      single kinase inhibitors can be fought using compounds which target multiple
      kinases. This tactics can increase effectiveness of the inhibitors by the
      synergistic effect or help to diminish the likelihood of drug resistance. To
      date, several families of kinases are quite popular targets of the inhibition in
      cancers, such as tyrosine kinases, cycle-dependent kinases, mitogen-activated
      protein kinases, phosphoinositide 3-kinases as well as their pathway "players"
      and aurora kinases. Aurora kinases play an important role in the control of the
      mitosis and are often altered in diverse human cancers. Here, we will describe
      the most interesting multi-kinase inhibitors which inhibit aurora kinases among
      other targets and their use in preclinical and clinical cancer studies. 

PMID- 27038474
TI  - The Risk Factors and Characteristics of COPD Among Nonsmokers in Korea: An
      Analysis of KNHANES IV and V.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is increasing in prevalence
      and mortality. This study evaluated the prevalence, risk factors,
      characteristics, and health-related quality of life (HRQoL) of COPD among
      nonsmokers in Korea. METHODS: This was a population-based cross-sectional study
      using data obtained from the Fourth and Fifth Korean National Health and
      Nutrition Examination Survey, which was conducted from 2007 to 2011. RESULTS: A
      total of 15,063 participants completely answered the questionnaire and performed
      the spirometry. Among them, 59.6 % were nonsmokers and 40.4 % were smokers. The
      prevalence of nonsmoker COPD was 7.1 %. On multivariate analysis, age >=65 years
      (OR, 2.93; 95 % CI, 2.44-3.51), male sex (OR, 2.98; 95 % CI, 2.40-3.71), living
      in rural area (OR, 1.26; 95 % CI, 1.05-1.51), lower body mass index (BMI) (<18.5
      kg/m(2)) (OR, 3.00; 95 % CI, 1.78-5.01), self-reported asthma (OR, 2.72; 95 % CI,
      2.05-3.60), and self-reported tuberculosis (OR, 4.73; 95 % CI, 3.63-6.17) showed
      a significantly higher risk of nonsmoker COPD. Analysis of nonsmoker and smoker
      COPD revealed that there are more females in nonsmoker COPD patients (73.9 vs.
      6.9 %, P < 0.001). Nonsmoker COPD patients presented with impaired mobility,
      pain/discomfort, and anxiety/depression functions as well as a lower mean EuroQol
      Five-Dimension Questionnaire utility score, which showed HRQoL. CONCLUSIONS: The
      burden of nonsmoker COPD was considerable. Older age, male sex, lower BMI, self
      reported asthma, and self-reported tuberculosis were risk factors for nonsmoker
      COPD and there were differences between nonsmoker and smoker COPD in terms of
      sex, comorbidities, and HRQoL.

PMID- 27038475
TI  - Identification and Characterization of a delta-Cadinol Synthase Potentially
      Involved in the Formation of Boreovibrins in Boreostereum vibrans of
      Basidiomycota.
AB  - Sesquiterpenoids are very common among natural products. A large number of
      sesquiterpene synthase genes have been cloned and functionally characterized.
      However, until now there is no report about the delta-cadinol synthase
      predominantly forming delta-cadinol (syn. torreyol) from farnesyl diphosphate.
      Sesquiterpenoids boreovibrins structurally similar to delta-cadinol were
      previously isolated from culture broths of the basidiomycete fungus Boreostereum
      vibrans. This led us to expect a corresponding gene coding for a delta-cadinol
      synthase that may be involved in the biosynthesis of boreovibrins in B. vibrans.
      Here we report the cloning and heterologous expression of a new sesquiterpene
      synthase gene from B. vibrans. The crude and purified recombinant enzymes, when
      incubating with farnesyl diphosphate as substrate, gave delta-cadinol as its
      principal product and thereby identified as a delta-cadinol synthase. A new
      sesquiterpene synthase gene was cloned from the basidiomycete fungus Boreostereum
      vibrans and heterologously expressed in E. coli. The purified recombinant enzyme
      gave delta-cadinol as its principal product from farnesyl diphosphate and thereby
      identified as a delta-cadinol synthase (BvCS). 

PMID- 27038476
TI  - Blood lead concentrations in free-ranging Nile crocodiles (Crocodylus niloticus)
      from South Africa.
AB  - Generally crocodilians have received little attention with regard to the effects
      of lead toxicity despite their trophic status as apex, generalist predators that
      utilize both aquatic and terrestrial habitats, thereby exposing them to a
      potentially wide range of environmental contaminants. During July-October 2010 we
      collected whole blood from 34 sub-adult and adult free-ranging Nile crocodiles
      (Crocodylus niloticus) from three separate populations in northeastern South
      Africa in order to analyze their blood lead concentrations (BPb). Concentrations
      ranged from below detectability (<3 MUg/dL, n = 8) to 960 MUg/dL for an adult
      male at the Lake St Lucia Estuary. Blood lead concentrations averaged 8.15 MUg/dL
      (SD = 7.47) for females and 98.10 MUg/dL (SD = 217.42) for males. Eighteen
      individuals (53 %) had elevated BPbs (>=10 MUg/dL). We assessed 12 general linear
      models using Akaike's Information Criterion (AIC) and found no significant
      statistical effects among the parameters of sex, crocodile size and population
      sampled. On average, crocodiles had higher BPbs at Lake St Lucia than at Ndumo
      Game Reserve or Kosi Bay, which we attribute to lead sinker ingestion during
      normal gastrolith acquisition. No clinical effects of lead toxicosis were
      observed in these crocodiles, even though the highest concentration (960 MUg/dL)
      we report represents the most elevated BPb recorded to date for a free-ranging
      vertebrate. Although we suggest adult Nile crocodiles are likely tolerant of
      elevated Pb body burdens, experimental studies on other crocodilian species
      suggest the BPb levels reported here may have harmful or fatal effects to egg
      development and hatchling health. In light of recent Nile crocodile nesting
      declines in South Africa we urge further BPb monitoring and ecotoxicology
      research on reproductive females and embryos. 

PMID- 27038477
TI  - Cadmium induced oxidative damage and apoptosis in the hepatopancreas of Meretrix
      meretrix.
AB  - Even trace amounts of cadmium (Cd), a non-essential metal, are known to be toxic
      to aquatic organisms. Here we investigated the relationship between cadmium ion
      (Cd(2+)) exposure and oxidative damage and apoptosis in the hepatopancreas of the
      clam Meretrix meretrix. Clams were exposed to different concentrations of Cd(2+)
      (0, 1.5, 3, 6 and 12 mg L(-1)) for 5 days. We monitored both antioxidant enzyme
      activity, including that of superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidases (GPx), and levels of malondialdehyde (MDA), glutathione
      (GSH) and glutathione disulfide (GSSG). Apoptosis of hepatopancreatic cells was
      detected by DNA laddering and AO/EB double fluorescent staining. The results show
      that the rate of apoptotis, MDA levels, and caspase-3 activity, increased with
      Cd(2+) concentration, whereas GPx activity and the ratio of GSH/GSSG, decreased.
      SOD and CAT enzyme activity first increased, then decreased, with increasing
      Cd(2+) concentration; peak activity of these enzymes was recorded in the 3 mg L(
      1) Cd(2+)-treatment group. These results show that Cd-induced oxidative damage
      can both induce, and aggravate, apoptosis in the hepatopancreatic cells of clams,
      even at Cd(2+) concentrations far below the semi-lethal dose for adult clams. The
      observed changes in caspase-3 activity enhanced significantly at lower Cd(2+)
      concentrations, indicating that caspase-3 is a suitable biomarker for heavy metal
      pollution, especially cadmium pollution, in marine organisms. 

PMID- 27038478
TI  - The effects of medial synovial plica excision with and without lateral
      retinacular release on adolescents with anterior knee pain.
AB  - OBJECTIVES: To describe the functional outcomes in patients aged <=18 years with
      anterior knee pain treated with medial plica excision with or without lateral
      release. METHODS: We identified 135 patients including 30 bilateral cases (165
      knees) with a mean +/- SD age of 15.1 +/- 2.0 years. Patient and surgical
      information was recorded and a follow-up athletic questionnaire and an
      International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form
      were sent out. Statistical analysis evaluated predictors of residual pain,
      reoperation, return to sports, IKDC score and satisfaction with surgery. RESULTS:
      At a final mean follow-up of 4.4 years (range 2-7.5), 36 % of patients were pain
      free, 46 % had mild residual pain and 18 % had pain not improved from surgery.
      Reoperation was more likely following isolated plica excision (7/41; 17 %) versus
      plica excision with lateral release (8/124; 6 %), although not statistically
      significant, P = 0.06. Mean IKDC score (107 knees) was 76.9 +/- 17.8 (range 31
      100). Most patients (86/99; 87 %) were satisfied with surgery and were able to
      return to sports (104/120; 87 %). CONCLUSIONS: While most patients were satisfied
      and able to return to sports following plica excision with or without lateral
      release, residual symptoms were common.

PMID- 27038479
TI  - Erratum to: The Intensive Care Global Study on Severe Acute Respiratory Infection
      (IC-GLOSSARI): a multicenter, multinational, 14-day inception cohort study.

PMID- 27038480
TI  - Experts' opinion on management of hemodynamics in ARDS patients: focus on the
      effects of mechanical ventilation.
AB  - RATIONALE: Acute respiratory distress syndrome (ARDS) is frequently associated
      with hemodynamic instability which appears as the main factor associated with
      mortality. Shock is driven by pulmonary hypertension, deleterious effects of
      mechanical ventilation (MV) on right ventricular (RV) function, and associated
      sepsis. Hemodynamic effects of ventilation are due to changes in pleural pressure
      (Ppl) and changes in transpulmonary pressure (TP). TP affects RV afterload,
      whereas changes in Ppl affect venous return. Tidal forces and positive end
      expiratory pressure (PEEP) increase pulmonary vascular resistance (PVR) in direct
      proportion to their effects on mean airway pressure (mPaw). The acutely injured
      lung has a reduced capacity to accommodate flowing blood and increases of blood
      flow accentuate fluid filtration. The dynamics of vascular pressure may
      contribute to ventilator-induced injury (VILI). In order to optimize perfusion,
      improve gas exchange, and minimize VILI risk, monitoring hemodynamics is
      important. RESULTS: During passive ventilation pulse pressure variations are a
      predictor of fluid responsiveness when conditions to ensure its validity are
      observed, but may also reflect afterload effects of MV. Central venous pressure
      can be helpful to monitor the response of RV function to treatment.
      Echocardiography is suitable to visualize the RV and to detect acute cor
      pulmonale (ACP), which occurs in 20-25 % of cases. Inserting a pulmonary artery
      catheter may be useful to measure/calculate pulmonary artery pressure, pulmonary
      and systemic vascular resistance, and cardiac output. These last two indexes may
      be misleading, however, in cases of West zones 2 or 1 and tricuspid regurgitation
      associated with RV dilatation. Transpulmonary thermodilution may be useful to
      evaluate extravascular lung water and the pulmonary vascular permeability index.
      To ensure adequate intravascular volume is the first goal of hemodynamic support
      in patients with shock. The benefit and risk balance of fluid expansion has to be
      carefully evaluated since it may improve systemic perfusion but also may decrease
      ventilator-free days, increase pulmonary edema, and promote RV failure. ACP can
      be prevented or treated by applying RV protective MV (low driving pressure,
      limited hypercapnia, PEEP adapted to lung recruitability) and by prone
      positioning. In cases of shock that do not respond to intravascular fluid
      administration, norepinephrine infusion and vasodilators inhalation may improve
      RV function. Extracorporeal membrane oxygenation (ECMO) has the potential to be
      the cause of, as well as a remedy for, hemodynamic problems. Continuous
      thermodilution-based and pulse contour analysis-based cardiac output monitoring
      are not recommended in patients treated with ECMO, since the results are
      frequently inaccurate. Extracorporeal CO2 removal, which could have the
      capability to reduce hypercapnia/acidosis-induced ACP, cannot currently be
      recommended because of the lack of sufficient data.

PMID- 27038481
TI  - The influence of maternal and paternal history on stone composition and clinical
      course of calcium nephrolithiasis in subjects aged between 15 and 25.
AB  - Our aim was to compare the influence of maternal history of stones (MHS) and
      paternal history of stones (PHS) on composition of calculi and disease course in
      a group of patients with calcium nephrolithiasis (CN) aged between 15 and 25, the
      age range with the maximal influence of family history on disease expression. One
      hundred thirty-five patients (68 F) with CN and one stone-forming parent were
      retrospectively selected from the database of our outpatient stone clinic, and
      categorized according to MHS or PHS. Data about stone disease course and
      composition of passed calculi, determined by chemical analysis or Fourier
      transformed infrared spectrophotometry, were collected together with information
      on blood chemistry and 24-h urinary profile of lithogenic risk. The
      characteristics of disease course and stone composition were compared using
      logistic regression tests adjusted for age, sex, and BMI or analysis of
      covariance where appropriate. Patients with MHS (n = 46) had significantly higher
      urinary calcium/creatinine ratio and ammonium, a higher prevalence of urological
      treatments (57 vs 27 %, p < 0.001) and mixed calcium oxalate/calcium phosphate
      stone composition (69 vs 35 %, p = 0.002) than those with PHS. At multivariate
      logistic regression models, MHS was independently associated with urological
      treatments (OR 4.5, 95 %CI 1.9-10.7, p < 0.001) and the formation of calculi with
      mixed calcium oxalate/calcium phosphate composition (OR 5.8, 95 %CI 1.9-17.9, p =
      0.002). The method of stone analysis did not affect this result. In conclusion,
      in subjects aged 15-25, MHS is associated with mixed calcium stones and with a
      higher risk for urological procedures, and should be, therefore, considered in
      the management of urolithiasis.

PMID- 27038482
TI  - Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in
      Global Catfish Aquaculture.
AB  - Catfish is one of the most cultivated species worldwide. Antibiotics are usually
      used in catfish farming as therapeutic and prophylactic agents. In the USA, only
      oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and
      florfenicol are approved by the Food Drug Administration for specific fish
      species (e.g., catfish and salmonids) and their specific diseases. Misuse of
      antibiotics as prophylactic agents in disease prevention, however, is common and
      contributes in the development of antibiotic resistance. Various studies had
      reported on antibiotic residues and/or resistance in farmed species, feral fish,
      water column, sediments, and, in a lesser content, among farm workers. Ninety
      percent of the world aquaculture production is carried out in developing
      countries, which lack regulations and enforcement on the use of antibiotics.
      Hence, efforts are needed to promote the development and enforcement of such a
      regulatory structure. Alternatives to antibiotics such as antibacterial vaccines,
      bacteriophages and their lysins, and probiotics have been applied to curtail the
      increasing emergence of antibiotic-resistant bacteria due to the imprudent
      application of antibiotics in aquaculture. 

PMID- 27038483
TI  - Investigation of Biowaivers for Immediate Release Formulations Containing BCS III
      Drugs, Acyclovir, Atenolol, and Ciprofloxacin Hydrochloride, Using Dissolution
      Testing.
AB  - The dissolution of several products containing Biopharmaceutical Classification
      System (BCS) class III drugs, acyclovir, atenolol, and ciprofloxacin
      hydrochloride, listed in the WHO essential drug list (EDL), was tested and
      compared with their respective comparator pharmaceutical products (CPPs) marketed
      in South Africa and India. US Pharmacopeia (USP) buffers of pH 1.2, 4.5, and 6.8
      were used as dissolution media and tested using USP apparatus 2 at 75 rpm and 900
      ml. Nine acyclovir products were tested, and only three dissolved very rapidly in
      all media; i.e., they showed a release of >85% in 15 min. Eight atenolol products
      tested were all very rapidly dissolving in all three pH media. Ten ciprofloxacin
      hydrochloride products were tested, and the results showed that only five
      products met the WHO biowaiver criteria. This study indicates that not all
      marketed products containing the same BCS III active pharmaceutical ingredient
      (API) in similar strength and dosage form are necessarily in vitro equivalent as
      per the WHO biowaiver criteria. Furthermore, selection and availability of an
      innovator product as CPP are important considerations that can affect the
      outcomes of such studies.

PMID- 27038484
TI  - Comparative Study Between Different Ready-Made Orally Disintegrating Platforms
      for the Formulation of Sumatriptan Succinate Sublingual Tablets.
AB  - Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the
      treatment of migraine attacks, suffering from extensive first-pass metabolism and
      low oral bioavailability (~14%). The aim of this work is to compare the
      performance of different ready-made co-processed platforms (Pharmaburst(r),
      Prosolv ODT(r), Starlac(r), Pearlitol Flash(r), or Ludiflash(r)) in the
      formulation of SS sublingual orodispersible tablets (ODTs) using direct
      compression technique. The prepared SS ODT formulae were evaluated regarding
      hardness, friability, simulated wetting time, and in vitro disintegration and
      dissolution tests. Different mucoadhesive polymers-HPMC K4M, Carbopol(r),
      chitosan, or Polyox(r)-were tested aiming to increase the residence time in the
      sublingual area. A pharmacokinetic study on healthy human volunteers was
      performed, using LC/MS/MS assay, to compare the optimum sublingual formula
      (Ph25/HPMC) with the conventional oral tablet Imitrex(r). Results showed that
      tablets prepared using Pharmaburst(r) had significantly (p < 0.05) the lowest
      simulated wetting and in vitro disintegration times of 17.17 and 23.50 s,
      respectively, with Q 5 min of 83.62%. HPMC showed a significant (p < 0.05)
      increase in the residence time from 48.44 to 183.76 s. The relative
      bioavailability was found to be equal to 132.34% relative to the oral tablet
      Imitrex(r). In conclusion, Pharmaburst(r) was chosen as the optimum ready-made co
      processed platform that can be successfully used in the preparation of SS
      sublingual tablets for the rapid relief of migraine attacks.

PMID- 27038485
TI  - VEGF receptor-2-specific signaling mediated by VEGF-E induces hemangioma-like
      lesions in normal and in malignant tissue.
AB  - Viral VEGF-E (ovVEGF-E), a homolog of VEGF-A, was discovered in the genome of Orf
      virus. Together with VEGF-A, B, C, D, placental growth factor (PlGF) and snake
      venom VEGF (svVEGF), ovVEGF-E is a member of the VEGF family of potent
      angiogenesis factors with a bioactivity similar to VEGF-A: it induces
      proliferation, migration and sprouting of cultured vascular endothelial cells and
      proliferative lesions in the skin of sheep, goat and man that are characterized
      by massive capillary proliferation and dilation. These biological functions are
      mediated exclusively via its interaction with VEGF receptor-2 (VEGFR-2). Here, we
      have generated transgenic mice specifically expressing ovVEGF-E in beta-cells of
      the endocrine pancreas (Rip1VEGF-E; RVE). RVE mice show an increase in number and
      size of the islets of Langerhans and a distorted organization of insulin and
      glucagon-expressing cells. Islet endothelial cells of RVE mice hyper-proliferate
      and form increased numbers of functional blood vessels. In addition, the
      formation of disorganized lymphatic vessels and increased immune cell
      infiltration is observed. Upon crossing RVE single-transgenic mice with Rip1Tag2
      (RT2) transgenic mice, a well-studied model of pancreatic beta-cell
      carcinogenesis, double-transgenic mice (RT2;RVE) display hyper-proliferation of
      endothelial cells resulting in the formation of hemangioma-like lesions. In
      addition, RT2;RVE mice exhibit activated lymphangiogenesis at the tumor periphery
      and increased neutrophil and macrophage tumor infiltration and micro-metastasis
      to lymph nodes and lungs. These phenotypes markedly differ from the phenotypes
      observed with the transgenic expression of the other VEGF family members in beta
      cells of normal mice and of RT2 mice.

PMID- 27038486
TI  - alpha2-6 sialylation is a marker of the differentiation potential of human
      mesenchymal stem cells.
AB  - Human somatic stem cells such as human mesenchymal stem cells (hMSCs) are
      considered attractive cell sources for stem cell-based therapy. However, quality
      control issues have been raised concerning their safety and efficacy. Here we
      used lectin microarray technology to identify cell surface glycans as markers of
      the differentiation potential of stem cells. We found that alpha2-6Sia-specific
      lectins show stronger binding to early passage adipose-derived hMSCs (with
      differentiation ability) than late passage cells (without the ability to
      differentiate). Flow cytometry analysis using alpha2-6Sia-specific lectins
      supported the results obtained by lectin microarray. Similar results were
      obtained for bone marrow-derived hMSCs and cartilage tissue-derived chondrocytes.
      Little or no binding of alpha2-6Sia-specific lectins was observed for human
      dermal fibroblasts, which are unable to differentiate, suggesting that the
      binding of alpha2-6Sia-specific lectins is associated with the differentiation
      ability of cells, but not to their capacity to proliferate. Quantitative analysis
      of the linkage mode of Sia using anion-exchange chromatography showed that the
      percentage of alpha2-6Sia linkage type was higher in early passage adipose
      derived hMSCs than late passage cells. Integrinalpha5 was found to be a carrier
      protein of alpha2-6Sia. Sialidase treatment significantly reduced the
      differentiation efficiency of bone marrow-derived hMSCs. Based on these findings,
      we propose that alpha2-6sialylation is a marker of differentiation potential in
      stem cells such as adipose-derived hMSCs, bone marrow-derived hMSCs, and
      cartilage tissue-derived chondrocytes.

PMID- 27038488
TI  - MicroRNA degeneracy and pluripotentiality within a Lavalliere-tie architecture
      confers robustness to gene expression networks.
AB  - Modularity, feedback control, functional redundancy and bowtie architecture have
      been proposed as key factors that confer robustness to complex biological
      systems. MicroRNAs (miRNAs) are highly conserved but functionally dispensable.
      These antinomic properties suggest that miRNAs fine-tune gene expression rather
      than act as genetic switches. We synthesize published and unpublished data and
      hypothesize that miRNA pluripotentiality acts to buffer gene expression, while
      miRNA degeneracy tunes the expression of targets, thus providing robustness to
      gene expression networks. Furthermore, we propose a Lavalliere-tie architecture
      by integrating signal transduction, miRNAs and protein expression data to model
      complex gene expression networks.

PMID- 27038489
TI  - Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as
      measures of response in osteoarthritis.
AB  - OBJECTIVE: Synovium is increasingly a target of osteoarthritis (OA) treatment,
      yet its optimal measurement is unclear. Using dynamic contrast enhanced (DCE) MRI
      in knee OA patients before and after intraarticular steroid injection, we
      compared the responsiveness of static synovial volume measures to measures of
      dynamic changes in synovial enhancement, changes that are strongly related to
      synovial vascularity. METHODS: Ninety three patients underwent DCE-MRI before and
      1-2 weeks after intra-articular injection of 80 mg methylprednisolone. Synovium
      was segmented and volume, relative enhancement rate (RER), maximum relative
      enhancement (REmax), late relative enhancement (RElate) and pharmacokinetic
      parameters (K(trans), ve) were calculated. KOOS (knee injury and osteoarthritis
      outcome score) pain score was recorded before and after injection. Standardized
      change scores were calculated for each parameter. Linear regression and Pearson's
      correlations were used to investigate the relationship between change in MRI
      parameters and change in pain. RESULTS: The change in standardized score for the
      measures of synovial enhancement, RElate and REmax were -0.58 (95% CI -0.79 to 
      0.37) and -0.62 (95% CI -0.83 to -0.41) respectively, whereas the score for
      synovial volume was -0.30 (-0.52 to -0.09). Further, change in knee pain
      correlated more strongly with changes in enhancement (for both REmax and RElate,
      r = -0.27 (95% CI -0.45 to -0.07)) than with changes in synovial volume -0.15 (
      0.35 to 0.05). CONCLUSION: This study suggests DCE-MRI derived measures of
      synovial enhancement may be more sensitive to the response to treatment and more
      strongly associated with changes in pain than synovial volume and may be better
      outcomes for assessment of structural effects of treatment in OA.

PMID- 27038490
TI  - Mechanical symptoms as an indication for knee arthroscopy in patients with
      degenerative meniscus tear: a prospective cohort study.
AB  - OBJECTIVE: According to prevailing consensus, patients with mechanical symptoms
      are those considered to most likely benefit from arthroscopic surgery. The aim of
      this study was to determine the value of using patients' pre-operative self
      reports of mechanical symptoms as a justification surgery in patients with
      degenerative meniscus tear/knee disease. DESIGN: Pragmatic prospective cohort of
      900 consecutive patients with symptomatic degenerative knee disease and meniscus
      tear undergoing arthroscopic partial meniscectomy (APM) was collected from one
      public orthopedic referral center specialized in arthroscopic surgery during 2007
      2011. The patients' subjective satisfaction, self-rated improvement, change in
      Western Ontario Meniscal Evaluation Tool (WOMET) score, and patients' ratings of
      the knee using a numerical rating scale (NRS) was assessed at 1 year
      postoperatively. Multivariable regression models, adjusted for possible
      confounders and intermediates, were used to compare the outcomes in those with
      and without preoperative mechanical symptoms. RESULTS: The proportion of patients
      satisfied with their knee 12 months after arthroscopy was significantly lower
      among those with preoperative mechanical symptoms than among those without (61%
      vs 75%, multivariable adjusted risk ratio [RR] 0.84; 95% confidence interval [CI]
      0.76, 0.92). Similarly, the proportion reporting improvement was lower (RR 0.91;
      95% CI 0.85, 0.97). No statistically significant difference was found in change
      in WOMET or NRS between the two groups. Of those with preoperative mechanical
      symptoms, 47% reported persistent symptoms at 12 months postoperatively.
      CONCLUSIONS: Our observational data contradicts the current tenet of using
      patients' self-report of mechanical symptoms as a justification for performing
      arthroscopic surgery on patients with degenerative meniscus tear.

PMID- 27038487
TI  - Mechanisms of T cell organotropism.
AB  - Protective immunity relies upon T cell differentiation and subsequent migration
      to target tissues. Similarly, immune homeostasis requires the localization of
      regulatory T cells (Tregs) to the sites where immunity takes place. While naive T
      lymphocytes recirculate predominantly in secondary lymphoid tissue, primed T
      cells and activated Tregs must traffic to the antigen rich non-lymphoid tissue to
      exert effector and regulatory responses, respectively. Following priming in
      draining lymph nodes, T cells acquire the 'homing receptors' to facilitate their
      access to specific tissues and organs. An additional level of topographic
      specificity is provided by T cells receptor recognition of antigen displayed by
      the endothelium. Furthermore, co-stimulatory signals (such as those induced by
      CD28) have been shown not only to regulate T cell activation and differentiation,
      but also to orchestrate the anatomy of the ensuing T cell response. We here
      review the molecular mechanisms supporting trafficking of both effector and
      regulatory T cells to specific antigen-rich tissues.

PMID- 27038491
TI  - Development and preliminary evaluation of the OsteoArthritis Questionnaire (OA
      Quest): a psychometric study.
AB  - OBJECTIVE: This study reports the development of the OsteoArthritis Questionnaire
      (OA-Quest) - a new measure designed to comprehensively capture the potentially
      modifiable burden of osteoarthritis. DESIGN: Item development was guided by the a
      priori conceptual framework of the Personal Burden of Osteoarthritis (PBO) which
      captures 8 dimensions of osteoarthritis burden (Physical distress, Fatigue,
      Physical limitations, Psychosocial distress, Physical de-conditioning, Financial
      hardship, Sleep disturbances, Lost productivity). One hundred and twenty three
      candidate items were pretested in a clinical sample of 18 osteoarthritis
      patients. The measurement properties of the OA-Quest were assessed with
      exploratory factor analysis (EFA), Rasch modelling, and confirmatory factor
      analysis (CFA) in a community-based sample (n = 792). RESULTS: EFA replicated 7
      of the 8 PBO domains. An exception was PBO Fatigue domain, with items merging
      into the Physical distress subscale in the OA-Quest. Following item analysis, a
      42-item 7-subscale questionnaire was constructed, measuring Physical distress
      (seven items, Cronbach's alpha = 0.93), Physical limitations (11 items, alpha =
      0.95), Psychosocial distress (seven items, alpha = 0.93), Physical de
      conditioning (four items, alpha = 0.87), Financial hardship (four items, alpha =
      0.93), Sleep disturbances (five items, alpha = 0.96), and Lost productivity (four
      items alpha = 0.90). A highly restricted 7-factor CFA model had excellent fit
      with the data (chi(2)(113) = 316.36, P < 0.001; chi-square/degrees of freedom =
      2.8; comparative fit index [CFI] = 0.97; root mean square error of approximation
      [RMSEA] = 0.07), supporting construct validity of the new measure. CONCLUSIONS:
      The OA-Quest is a new measure of osteoarthritis burden that is founded on a
      comprehensive conceptual model. It has strong evidence of construct validity and
      provides reliable measurement across a broad range of osteoarthritis burden.

PMID- 27038492
TI  - Hyperthyroidism.
AB  - Hyperthyroidism is characterised by increased thyroid hormone synthesis and
      secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical
      syndrome of excess circulating thyroid hormones, irrespective of the source. The
      most common cause of hyperthyroidism is Graves' disease, followed by toxic
      nodular goitre. Other important causes of thyrotoxicosis include thyroiditis,
      iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of
      excess thyroid hormones. Treatment options for Graves' disease include
      antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid
      drugs are not generally used long term in toxic nodular goitre, because of the
      high relapse rate of thyrotoxicosis after discontinuation. beta blockers are used
      in symptomatic thyrotoxicosis, and might be the only treatment needed for
      thyrotoxicosis not caused by excessive production and release of the thyroid
      hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post
      partum period are special circumstances that need careful assessment and
      treatment. 

PMID- 27038493
TI  - Local retention of antibodies in vivo with an injectable film embedded with a
      fluorogen-activating protein.
AB  - Herein we report an injectable film by which antibodies can be localized in vivo.
      The system builds upon a bifunctional polypeptide consisting of a fluorogen
      activating protein (FAP) and a beta-fibrillizing peptide (betaFP). The FAP domain
      generates fluorescence that reflects IgG binding sites conferred by Protein A/G
      (pAG) conjugated with the fluorogen malachite green (MG). A film is generated by
      mixing these proteins with molar excess of EAK16-II, a betaFP that forms beta
      sheet fibrils at high salt concentrations. The IgG-binding, fluorogenic film can
      be injected in vivo through conventional needled syringes. Confocal microscopic
      images and dose-response titration experiments showed that loading of IgG into
      the film was mediated by pAG(MG) bound to the FAP. Release of IgG in vitro was
      significantly delayed by the bioaffinity mechanism; 26% of the IgG were released
      from films embedded with pAG(MG) after five days, compared to close to 90% in
      films without pAG(MG). Computational simulations indicated that the release rate
      of IgG is governed by positive cooperativity due to pAG(MG). When injected into
      the subcutaneous space of mouse footpads, film-embedded IgG were retained
      locally, with distribution through the lymphatics impeded. The ability to track
      IgG binding sites and distribution simultaneously will aid the optimization of
      local antibody delivery systems.

PMID- 27038494
TI  - Selective non-zinc binding MMP-2 inhibitors: Novel benzamide Ilomastat analogs
      with anti-tumor metastasis.
AB  - Novel Ilomastat analogs with substituted benzamide groups, instead of hydroxamic
      acid groups, were designed, synthesized and evaluated against MMP-2 and MMP-9.
      Among these analogs, the most potent compound 10a exhibited potent inhibitory
      activity against MMP-2 with IC50 value of 0.19 nM, which is 5 times more potent
      than that of Ilomastat (IC50=0.94 nM). Importantly, 10a exhibited more than 8300
      fold selectivity for MMP-2 versus MMP-9 (IC50=1.58 MUM). Molecular docking
      studies showed that 10a bond to the catalytic active pocket of MMP-2 by a non
      zinc-chelating mechanism which was different from that of Ilomastat. Furthermore,
      the invasion assay showed that 10a was effective in reducing HEY cells invasion
      at 84.6% in 50 MUM concentration. For 10a, the pharmacokinetic properties had
      been improved and especially the more desirable t1/2z was achieved compared with
      these of the lead compound Ilomastat.

PMID- 27038495
TI  - Synthesis and biological evaluation of aryloxyacetamide derivatives as
      neuroprotective agents.
AB  - A series of new aryloxyacetamide derivatives 10a-s and 14a-m are designed and
      synthesized. Their protective activities against the glutamate-induced cell death
      were investigated in differentiated rat pheochromocytoma cells (PC12 cells). Most
      compounds exhibited neuroprotective effects, especially for 10m, 10r, 14b and
      14c, which showed potential protection of PC12 cells at three doses (0.1, 1.0,
      10MUM). MTT assay, Hoechst 33342/PI double staining, and high content screening
      (HCS) revealed that pretreatment of the cells with 10m, 10r, 14b and 14c has
      significantly decreased the extent of cell apoptosis in a dose-dependent manner.
      The results of western blot analysis demonstrated these compounds suppressed
      apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds
      can be lead compounds for further discovery of neuroprotective agents for
      treating cerebral ischemic stroke. Basic structure-activity relationships are
      also presented.

PMID- 27038496
TI  - Part 3: Notch-sparing gamma-secretase inhibitors: SAR studies of 2-substituted
      aminopyridopyrimidinones.
AB  - In search for novel lead compounds as gamma-secretase inhibitors, analogs of
      aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for
      inhibitory effects on amyloid-beta-peptide production and cleavage of the Notch1
      receptor mediated by gamma-secretase. Selected pyridopyrimidines, such as 1, 8,
      9, 10, 11 and 16 are gamma-secretase inhibitors that did not have an effect on
      Notch1 receptor processing. 

PMID- 27038497
TI  - Nitric oxide production inhibition and mechanism of phenanthrene analogs in
      lipopolysaccharide-stimulated RAW264.7 macrophages.
AB  - Natural phenanthrene derivatives are considered to be important resource for the
      anti-inflammatory therapeutics, but their structure-activity relationship and
      mechanisms are still unknown. In this study we evaluated 20 synthesized
      phenanthrene analogs in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages.
      Compounds 10, 11 and 17 were found to inhibit the production of nitric oxide (NO)
      with IC50 values of 37.26MUM, 5.05MUM and 20.31MUM, respectively. Compound 11
      decreased LPS-induced expression of inducible NO synthase (iNOS), inhibited
      phosphorylation of p38 mitogen-activated protein kinase (MAPK) and
      serine/threonine kinase Akt. It also suppressed the phosphorylation and
      degradation of inhibitory kappa B-alpha (IkappaBalpha). Data obtained suggest
      that compound 11 exerts anti-inflammatory effects by inhibiting p38 MAPK and
      nuclear factor kappaB (NF-kappaB) pathways, which warrants further investigation
      as a new anti-inflammatory pharmaceutical tool.

PMID- 27038498
TI  - Discovery of triazolopyridinone GS-462808, a late sodium current inhibitor (Late
      INai) of the cardiac Nav1.5 channel with improved efficacy and potency relative
      to ranolazine.
AB  - Previously we disclosed the discovery of potent Late INa current inhibitor 2 (GS
      458967, IC50 of 333nM) that has a good separation of late versus peak Nav1.5
      current, but did not have a favorable CNS safety window due to high brain
      penetration (3-fold higher partitioning into brain vs plasma) coupled with potent
      inhibition of brain sodium channel isoforms (Nav1.1, 1.2, 1.3). We increased the
      polar surface area from 50 to 84A(2) by adding a carbonyl to the core and an
      oxadiazole ring resulting in 3 GS-462808 that had lower brain penetration and
      serendipitously lower activity at the brain isoforms. Compound 3 has an improved
      CNS window (>20 rat and dog) relative to 2, and improved anti-ischemic potency
      relative to ranolazine. The development of 3 was not pursued due to liver lesions
      in 7day rat toxicology studies.

PMID- 27038499
TI  - The influence of the elements of procedural justice and speed camera enforcement
      on young novice driver self-reported speeding.
AB  - Road policing is an important tool used to modify road user behaviour. While
      other theories, such as deterrence theory, are significant in road policing,
      there may be a role for using procedural justice as a framework to improve
      outcomes in common police citizen interactions such as traffic law enforcement.
      This study, using a sample of 237 young novice drivers, considered how the four
      elements of procedural justice (voice, neutrality, respect and trustworthiness)
      were perceived in relation to two forms of speed enforcement: point-to-point (or
      average) speed and mobile speed cameras. Only neutrality was related to both
      speed camera types suggesting that it may be possible to influence behaviour by
      emphasising one or more elements, rather than using all components of procedural
      justice. This study is important as it indicates that including at least some
      elements of procedural justice in more automated policing encounters can
      encourage citizen compliance. 

PMID- 27038500
TI  - Investigation of work zone crash casualty patterns using association rules.
AB  - Investigation of the casualty crash characteristics and contributory factors is
      one of the high-priority issues in traffic safety analysis. In this paper, we
      propose a method based on association rules to analyze the characteristics and
      contributory factors of work zone crash casualties. A case study is conducted
      using the Michigan M-94/I-94/I-94BL/I-94BR work zone crash data from 2004 to
      2008. The obtained association rules are divided into two parts including rules
      with high-lift, and rules with high-support for the further analysis. The results
      show that almost all the high-lift rules contain either environmental or occupant
      characteristics. The majority of association rules are centered on specific
      characteristics, such as drinking driving, the highway with more than 4 lanes,
      speed-limit over 40mph and not use of traffic control devices. It should be
      pointed out that some stronger associated rules were found in the high-support
      part. With the network visualization, the association rule method can provide
      more understandable results for investigating the patterns of work zone crash
      casualties. 

PMID- 27038501
TI  - Brain injury tolerance limit based on computation of axonal strain.
AB  - Traumatic brain injury (TBI) is the leading cause of death and permanent
      impairment over the last decades. In both the severe and mild TBIs, diffuse
      axonal injury (DAI) is the most common pathology and leads to axonal
      degeneration. Computation of axonal strain by using finite element head model in
      numerical simulation can enlighten the DAI mechanism and help to establish
      advanced head injury criteria. The main objective of this study is to develop a
      brain injury criterion based on computation of axonal strain. To achieve the
      objective a state-of-the-art finite element head model with enhanced brain and
      skull material laws, was used for numerical computation of real world head
      trauma. The implementation of new medical imaging data such as, fractional
      anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12
      healthy patients into the finite element brain model was performed to improve the
      brain constitutive material law with more efficient heterogeneous anisotropic
      visco hyper-elastic material law. The brain behavior has been validated in terms
      of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in
      terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992)
      experiments. Verification of model stability has been conducted as well. Further,
      109 well-documented TBI cases were simulated and axonal strain computed to derive
      brain injury tolerance curve. Based on an in-depth statistical analysis of
      different intra-cerebral parameters (brain axonal strain rate, axonal strain,
      first principal strain, Von Mises strain, first principal stress, Von Mises
      stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal
      strain was the most appropriate candidate parameter to predict DAI. The proposed
      brain injury tolerance limit for a 50% risk of DAI has been established at 14.65%
      of axonal strain. This study provides a key step for a realistic novel injury
      metric for DAI. 

PMID- 27038502
TI  - Cryptococcus tetragattii as a major cause of cryptococcal meningitis among HIV
      infected individuals in Harare, Zimbabwe.
AB  - OBJECTIVES: HIV-associated cryptococcal meningitis is commonly caused by
      Cryptococcus neoformans, whilst infections with Cryptococcus gattii sensu lato
      are historically rare. Despite available studies, little is known about the
      occurrence of C. gattii sensu lato infections among HIV-infected individuals in
      Zimbabwe. METHODS: In a prospective cohort, we investigated the prevalence of C.
      gattii sensu lato meningitis among HIV-infected patients (n = 74) in Harare,
      Zimbabwe. RESULTS: Of the 66/74 isolates confirmed by molecular characterization,
      16.7% (11/66) were found to be C. gattii sensu lato and 83.3% (55/66) C.
      neoformans sensu stricto. From one patient two phenotypically different C. gattii
      sensu lato colonies were cultured. The majority (n = 9/12; 75%) of the C. gattii
      sensu lato isolates were Cryptococcus tetragattii (AFLP7/VGIV), which has been an
      infrequently reported pathogen. In-hospital mortality associated with C. gattii
      sensu lato was 36.4%. CONCLUSIONS: Our data suggests that C. tetragattii
      (AFLP7/VGIV) is a more common cause of disease than C. gattii sensu stricto
      (genotype AFLP4/VGI) among patients with HIV-associated cryptococcal meningitis
      in Harare, Zimbabwe and possibly underreported in sub-Saharan Africa.

PMID- 27038503
TI  - Genetic evolution of Human Enterovirus A71 subgenotype C4 in Shenzhen, China,
      1998-2013.
AB  - BACKGROUND: Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses
      that causes hand, foot, and mouth disease (HFMD) among children. This study
      identified the mutations of EV-A71 VP1 amino acid residues over a number of years
      and explored the possible association of identified mutations and HFMD epidemic
      outbreaks in Shenzhen, China. METHODS: A total of 3760 stool specimens were
      collected from HFMD patients by Shenzhen Centers for Disease Control and
      Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced
      in this study, and amino acids mutation frequency was calculated. There were 2040
      China nationwide sequences downloaded from Genebank as replication data. RESULTS:
      In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid
      positions on VP1 protein were found to have high mutation prevalence. These are
      Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008,
      at the time of the large scale epidemic outbreak in Shenzhen. Analysis of the
      nationwide data replicated the same trend of mutation prevalence of the three
      sites. CONCLUSION: The switching from Q to H on site 22 of the EV-A71 VP1 strain
      might be associated with the HFMD outbreak in Shenzhen in 2008. The identified
      amino acid sites 22, 283 and 289 provided information for developing anti-viral
      drugs against EV-A71 in the future.

PMID- 27038504
TI  - WITHDRAWN: The MSX1 gene polymorphisms rs12532 and rs1001179 confer an increased
      risk of non syndromic orofacial clefts.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 27038505
TI  - Stress Testing After Complete and Successful Coronary Revascularization.
AB  - BACKGROUND: Noninvasive stress tests play a determinant role in the initial
      management of patients with chronic angina. Nonetheless, their use in the same
      patient population is considered inappropriate within 2 years after percutaneous
      coronary intervention (PCI). Indeed, early abnormal results correlate less well
      with angiographic control and are attributed to a number of confounding factors.
      We prospectively assessed prevalence and impact on the quality of life of
      abnormal stress test results in a highly selected patient population. METHODS:
      Patients with no cardiac comorbidities who underwent successful and complete PCI
      with stenting for typical angina and had an abnormal exercise stress test (EST)
      under guideline-directed medical treatment were administered the Seattle Angina
      Questionnaire (SAQ). Clinical evaluation, EST, and the SAQ were repeated at 1, 6,
      and 12 months after the index PCI. RESULTS: One hundred ninety-eight patients
      qualified and were included in the study (mean age, 64 years; 79% men). Although
      the majority had normal EST results or an increased threshold to angina, at 1
      month after the index PCI, 29% of patients still had an abnormal result. At 6 and
      12 months, 31% and 29% of patients had abnormal results, respectively. Quality-of
      life assessment by the SAQ showed consistent results, with persistent angina in
      one third of patients. Control angiography documented a critical lesion,
      attributable to in-stent coronary restenosis, in only 8% of patients.
      CONCLUSIONS: When stress testing is systematically performed after PCI, the
      prevalence of abnormal results is high and is associated with impaired quality of
      life. Prognostic significance along with the underlying pathophysiological
      mechanisms of such findings should be investigated.

PMID- 27038506
TI  - Impactful Clinical Trials of 2015: What Clinicians Need to Know.
AB  - Randomized clinical trials (RCTs) remain the foundation for assessing and
      introducing evidence-based therapies into cardiovascular (CV) medicine. In 2015,
      a number of RCTs were reported and published that have great potential to improve
      CV outcomes and thus to change clinical practice. We highlight the results and
      implications of major RCTs in the areas of acute coronary syndrome (ACS),
      interventional cardiology, atrial fibrillation, lipids, heart failure, diabetes,
      and hypertension. Among the trials we discuss, PEGASUS and DAPT provide guidance
      regarding the potential benefits and hazards of longer-term dual-antiplatelet
      therapy after percutaneous coronary intervention (PCI) or myocardial infarction
      (MI). The BRIDGE study evaluated the role of bridging patients with atrial
      fibrillation who underwent noncardiac surgery with low-molecular-weight heparin
      while temporarily discontinuing their oral anticoagulant. The REVERSE-AD trial
      addressed the highly relevant issue of the first reversal agent (idarucizumab)
      for the direct oral anticoagulant dabigatran. The IMPROVE-IT assessed the
      benefits of adding ezetimibe to a statin in patients with ACS. Coupled with the
      latest studies involving proprotein convertase subtilisin/kexin type 9
      inhibitors, the lipid field was particularly active in 2015. The year ended with
      major headlines in hypertension and diabetes. The SPRINT may lead to a new era in
      hypertension, with lowered blood pressure (BP) targets, and EMPA-REG became the
      first study ever to demonstrate a convincing reduction in CV events with a
      glucose-lowering agent, in this case empagliflozin. The results of these and
      other trials will likely impact practice guidelines and improve outcomes for our
      patients.

PMID- 27038507
TI  - Protein Elongation, Co-translational Folding and Targeting.
AB  - The elongation phase of protein synthesis defines the overall speed and fidelity
      of protein synthesis and affects protein folding and targeting. The mechanisms of
      reactions taking place during translation elongation remain important questions
      in understanding ribosome function. The ribosome-guided by signals in the mRNA
      can recode the genetic information, resulting in alternative protein products. Co
      translational protein folding and interaction of ribosomes and emerging
      polypeptides with associated protein biogenesis factors determine the quality and
      localization of proteins. In this review, we summarize recent findings on
      mechanisms of translation elongation in bacteria, including decoding and
      recoding, peptide bond formation, tRNA-mRNA translocation, co-translational
      protein folding, interaction with protein biogenesis factors and targeting of
      ribosomes synthesizing membrane proteins to the plasma membrane. The data provide
      insights into how the ribosome shapes composition and quality of the cellular
      proteome.

PMID- 27038508
TI  - The Details of Glycolipid Glycan Hydrolysis by the Structural Analysis of a
      Family 123 Glycoside Hydrolase from Clostridium perfringens.
AB  - Clostridium perfringens is an opportunistic pathogen of humans and animals whose
      genome encodes a wide variety of putative carbohydrate-hydrolyzing enzymes that
      are increasingly being shown to be directed toward the cleavage of host glycans.
      Among these putative enzymes is a member of glycoside hydrolase family 123. Here
      we show that the recombinant enzyme (referred to as CpNga123) encoded by the gene
      cloned from C. perfringens strain ATCC 13124 (locus tag CPF_1473) is a beta-N
      acetylgalactosaminidase, similar to NgaP from Paenibacillus sp. TS12. Like NgaP,
      CpNga123 was able to cleave the terminal beta-D-GalNAc-(1->4)-D-Gal and beta-D
      GalNAc-(1->3)-D-Gal motifs that would be found in glycosphigolipids. The X-ray
      crystal structure of CpNga123 revealed it to have an N-terminal beta-sandwich
      domain and a (beta/alpha)8-barrel catalytic domain with a C-terminal alpha
      helical elaboration. The structures determined in complex with reaction products
      provide details of the -1 subsite architecture, catalytic residues, and a
      structural change in the active site that is likely required to enable hydrolysis
      of the glycosidic bond by promoting engagement of the substrate by the catalytic
      residues. The features of the active site support the likelihood of a substrate
      assisted catalytic mechanism for this enzyme. The structures of an inactive
      mutant of CpNga123 in complex with intact GA2 and Gb4 glycosphingolipid motifs
      reveal insight into aglycon recognition and suggest that the kinked or pleated
      conformation of GA2 caused by the beta-1,4-linkage between N-acetylgalactosamine
      and galactose, and the accommodation of this conformation by the enzyme active
      site, may be responsible for greater activity on GA2.

PMID- 27038509
TI  - Thermostabilization of the Human Endothelin Type B Receptor.
AB  - The peptide hormone endothelin, produced by the vascular endothelium, is involved
      in several physiological functions, including maintenance of vascular tone and
      humoral homeostasis. Endothelin transmits signals through the endothelin
      receptor, a G-protein-coupled receptor. Structural studies of the endothelin type
      B receptor (ETBR) have been unsuccessful due to its structural flexibility and
      instability in detergent-solubilized solution. To overcome these problems, we
      explored thermostabilization of human ETBR by establishing an ETBR expression
      system in Escherichia coli, followed by systematic alanine scanning mutagenesis.
      Among 297 point mutations, 11 thermostabilizing residues were selected and
      further mutated to other amino acids. The thermostability indices of these
      residues, represented by the ratios of endothelin-1 (ET-1) binding activities
      with or without heat treatment at 27 degrees C for 30min in a ligand-free form,
      were compared. The ligand affinity and apparent melting temperature (Tm) of the
      five most thermostable mutants, R124Y, D154A, K270A, S342A, and I381A, were then
      examined. The apparent Tm of three single mutants, R124Y, D154A, and K270A, was
      approximately 7 degrees C higher than that of the wild type. The apparent Tm
      value of a combination of the five residues, named the Y5 ETBR mutant, was 17
      degrees C higher than that of the wild type. The Y5 ETBR mutant exhibited an
      affinity for ET-1 and activated Gq similar to the wild type. Further
      investigation of the pharmacological properties affected by combinatorial
      mutations of ET-1, ET-3, TxET-1, and K8794 suggested that Y5 ETBR is highly
      suitable for representing a ligand-free form of ETBR and is potentially
      applicable for studying an ET-1-bound form.

PMID- 27038510
TI  - Shaping the Immune Landscape in Cancer by Galectin-Driven Regulatory Pathways.
AB  - Along with the discovery of tumor-driven inflammatory pathways, there has been a
      considerable progress over the past 10years in understanding the mechanisms
      leading to cancer immunosurveillance and immunoediting. Several regulatory
      pathways, typically involved in immune cell homeostasis, are co-opted by cancer
      cells to thwart the development of effective antitumor responses. These
      regulatory circuits include the engagement of inhibitory checkpoint pathways
      (CTLA-4, PD-1/PD-L1, LAG-3 and TIM-3), secretion of immunosuppressive cytokines
      (TGF-beta, IL-10), and expansion and/or recruitment of myeloid or lymphoid
      regulatory cell populations. Elucidation of these pathways has inspired the
      design and implementation of novel immunotherapeutic modalities, which have
      already generated clinical benefits in an important number of cancer patients.
      Galectins, a family of glycan-binding proteins widely expressed in the tumor
      microenvironment (TME), have emerged as key players in immune evasion programs
      that differentially control the fate of effector and regulatory lymphoid and
      myeloid cell populations. How do galectins translate glycan-containing
      information into cellular programs that control immune regulatory cancer
      networks? Here, we uncover the selective roles of individual members of the
      galectin family in cancer-promoting inflammation, immunosuppression, and
      angiogenesis. Moreover, we highlight the relevance of corresponding glycosylated
      ligands and counter-receptors and the emerging function of these lectins as
      biological liaisons connecting commensal microbiota, systemic inflammation, and
      distal tumor growth. Understanding the molecular and cellular components of
      galectin-driven regulatory circuits, the implications of different glycosylation
      pathways in their functions and their clinical relevance in human cancer might
      lead to the development of new therapeutic approaches in a broad range of tumor
      types.

PMID- 27038511
TI  - The Functional Role of eL19 and eB12 Intersubunit Bridge in the Eukaryotic
      Ribosome.
AB  - During translation, the two eukaryotic ribosomal subunits remain associated
      through 17 intersubunit bridges, five of which are eukaryote specific. These are
      mainly localized to the peripheral regions and are believed to stabilize the
      structure of the ribosome. The functional importance of these bridges remains
      largely unknown. Here, the essentiality of the eukaryote-specific bridge eB12 has
      been investigated. The main component of this bridge is ribosomal protein eL19
      that is composed of an N-terminal globular domain, a middle region, and a long C
      terminal alpha-helix. The analysis of deletion mutants demonstrated that the
      globular domain and middle region of eL19 are essential for cell viability, most
      likely functioning in ribosome assembly. The eB12 bridge, formed by contacts
      between the C-terminal alpha-helix of eL19 and 18S rRNA in concert with
      additional stabilizing interactions involving either eS7 or uS17, is dispensable
      for viability. Nevertheless, eL19 mutants impaired in eB12 bridge formation
      displayed slow growth phenotypes, altered sensitivity/resistance to translational
      inhibitors, and enhanced hyperosmotic stress tolerance. Biochemical analyses
      determined that the eB12 bridge contributes to the stability of ribosome subunit
      interactions in vitro. 60S subunits containing eL19 variants defective in eB12
      bridge formation failed to form 80S ribosomes regardless of Mg(2+) concentration.
      The reassociation of 40S and mutant 60S subunits was markedly improved in the
      presence of deacetylated tRNA, emphasizing the importance of tRNAs during the
      subunit association. We propose that the eB12 bridge plays an important role in
      subunit joining and in optimizing ribosome functionality. 

PMID- 27038512
TI  - Systolic and Diastolic Myocardial Response to Exercise in a Healthy Pediatric
      Cohort.
AB  - BACKGROUND: The aims of the present study were to evaluate the feasibility and
      reproducibility of color Doppler tissue imaging (DTI) and two-dimensional speckle
      tracking echocardiography during semisupine cycle ergometric stress
      echocardiography and to establish normal myocardial systolic and diastolic left
      ventricular (LV) and right ventricular (RV) response to exercise in children.
      METHODS: This was a single-center prospective study of 62 healthy children (35
      girls). The median age was 14 years (range, 8-19 years). A stepwise semisupine
      cycle ergometric protocol was used. Color DTI peak systolic (s') and peak
      diastolic (e') velocities and myocardial acceleration during isovolumic
      contraction were measured in the LV lateral wall, RV free wall, and septum. Early
      mitral inflow Doppler (E) was measured from the apical four-chamber view, and the
      ratio of diastolic filling to tissue early diastolic velocity (E/e') was
      calculated. LV and RV longitudinal strain were measured from four-chamber apical
      views. LV circumferential strain was derived from the parasternal short-axis view
      at the midventricular level. The relationship of each parameter with increasing
      heart rate was evaluated at each stage of exercise. RESULTS: During exercise
      color DTI, velocities were obtained in 96% of subjects, with isovolumic
      contraction having the lowest feasibility among DTI measurements (89%). Strain
      analysis was measurable in 87% of subjects, with LV longitudinal strain measured
      in 98% of the subjects compared with 93% for circumferential strain. RV
      longitudinal strain had the lowest feasibility (70%). A linear relationship was
      observed between heart rate and color DTI velocities, E, E/e', and myocardial
      longitudinal and circumferential strain. The relationship between isovolumic
      contraction and heart rate was exponential. CONCLUSIONS: This study provides
      reference values for systolic and diastolic reserve during exercise in healthy
      children as measured by color DTI and two-dimensional speckle-tracking
      echocardiography. These data allow the evaluation of myocardial response in
      pediatric cardiac disease.

PMID- 27038513
TI  - Detection of Carotid Atherosclerotic Plaque Neovascularization Using Contrast
      Enhanced Ultrasound: A Systematic Review and Meta-Analysis of Diagnostic Accuracy
      Studies.
AB  - BACKGROUND: Intraplaque neovascularization is considered an important indicator
      of plaque vulnerability. Contrast-enhanced ultrasound (CEUS) of carotid arteries
      improves imaging of carotid intima-media thickness and permits real-time
      visualization of neovascularization of the atherosclerotic plaque. The authors
      conducted a systematic review and meta-analysis to evaluate the accuracy of CEUS
      detected carotid atherosclerotic plaque. METHODS: A systematic search was
      performed to identify studies published in the MEDLINE, Embase, Scopus, and Web
      of Science databases from 2004 to June 2015. Studies evaluating the accuracy of
      quantitative analysis and qualitative analysis (visual interpretation) for the
      diagnosis of intraplaque neovascularization compared with histologic specimens
      and/or clinical diagnosis of symptomatic plaque were included. Parameters
      evaluated were plaque quantitative CEUS intensity and the visual grading of
      plaque CEUS. A random-effects meta-analysis was used to pool the likelihood
      ratios (LRs), diagnostic odds ratios, and summary receiver operating
      characteristic curves. Corresponding areas under the curves were calculated.
      RESULTS: The literature search identified 203 studies, 20 of which were selected
      for systematic review; the final meta-analysis included seven studies. For
      qualitative CEUS, pooled sensitivity was 0.80 (95% CI, 0.72-0.87), pooled
      specificity was 0.83 (95% CI, 0.76-0.89), the pooled positive LR was 3.22 (95%
      CI, 1.67-6.18), the pooled negative LR was 0.24 (95% CI, 0.09-0.64), the pooled
      diagnostic odds ratio was 15.57 (95% CI, 4.94-49.03), and area under the curve
      was 0.894. For quantitative CEUS, pooled sensitivity was 0.77 (95% CI, 0.71
      0.83), pooled specificity was 0.68 (95% CI, 0.62-0.73), the pooled positive LR
      was 2.34 (95% CI, 1.69-3.23), the pooled negative LR was 0.34 (95% CI, 0.25
      0.47), the pooled diagnostic odds ratio was 7.06 (95% CI, 3.6-13.82), and area
      under the curve was 0.888. CONCLUSIONS: CEUS is a promising noninvasive
      diagnostic modality for detecting intraplaque neovascularization. Standardization
      of quantitative analysis and visual grading classification is needed to increase
      reliability and reduce technical heterogeneity.

PMID- 27038514
TI  - Coronary Flow Velocity Reserve Assessed by Transthoracic Doppler: The iPOWER
      Study: Factors Influencing Feasibility and Quality.
AB  - BACKGROUND: Coronary flow velocity reserve (CFVR) measured by transthoracic
      Doppler echocardiography is a noninvasive measure of microvascular function, but
      it has not achieved widespread use, mainly because of concerns of validity and
      feasibility. The aim of this study was to describe the feasibility and factors
      associated with the quality of CFVR obtained in a large prospective study of
      women suspected of having microvascular disease. METHODS: Women with angina-like
      chest pain and no obstructive coronary artery disease on coronary angiography
      (<50% stenosis) were consecutively examined by transthoracic Doppler
      echocardiography of the left anterior descending coronary artery to measure CFVR
      (n = 947). Quality was evaluated on the basis of (1) identification of the left
      anterior descending coronary artery, (2) maintained probe position throughout the
      examination, (3) visibility and configuration of the left anterior descending
      coronary artery in two-dimensional color Doppler mode, and (4) gradual,
      consistent increases of characteristic, well-defined flow velocity curves in
      pulsed-wave mode. RESULTS: The mean age (SD) was 62.1 +/- 9.7 years. On the basis
      of the evaluations, patients were divided into four groups according to quality
      score: nonfeasible (n = 28 [3%]), low quality (n = 80 [8%]), medium quality (n =
      451 [48%]), and high quality (n = 388 [41%]). Quality score was associated with
      diabetes (P < .01), body mass index (P = .02), waist circumference (P = .05),
      nonsignificant atherosclerosis on coronary angiography (P = .03), and operator
      experience (P < .01). Low examination quality was associated with lower CFVR (P =
      .03), also after multivariate adjustment. CONCLUSIONS: Transthoracic Doppler
      echocardiographic measurement of CFVR is highly feasible and of good quality in
      experienced hands. However, CFVR is possibly underestimated when examination
      quality is low. Awareness of pitfalls and potential bias may improve the validity
      and interpretation of the measures obtained.

PMID- 27038515
TI  - Impaired Right Ventricular Function in Long-Term Lymphoma Survivors.
AB  - BACKGROUND: Cardiotoxicity from anthracyclines or cardiac radiation therapy is
      detrimental to left ventricular (LV) function. However, the long-term effects on
      right ventricular (RV) performance are largely unknown. The aim of this study was
      to investigate the long-term impact of cardiotoxic treatment on RV function among
      adult cancer survivors. METHODS: Adult lymphoma survivors (LSs) who underwent
      autologous hematopoietic stem cell transplantation in Norway from 1987 to 2008
      were invited to undergo cardiovascular evaluation by echocardiography and
      cardiopulmonary exercise testing. In total, 274 LSs participated. The mean age
      was 56 +/- 12 years, and the mean follow-up time since lymphoma diagnosis was 13
      +/- 6 years. Echocardiographic parameters were compared with those of age- and
      gender-matched control subjects from an existing large Norwegian database. RV
      systolic dysfunction was indicated by two or more abnormal RV systolic parameters
      according to current recommendations. LV systolic dysfunction was indicated by LV
      global longitudinal strain > -17%. RESULTS: All parameters of RV systolic
      function were impaired in LSs compared with control subjects (P < .01 for all).
      The most pronounced difference was observed for tricuspid annular plane systolic
      excursion: 22.9 +/- 4.1 versus 27.1 +/- 4.2 mm. Greater cardiotoxic treatment
      burden was associated with larger RV functional impairment. Tricuspid annular
      plane systolic excursion correlated with peak oxygen consumption (r = 0.23, P =
      .001). RV systolic performance was associated with LV systolic function (r =
      0.49, P < .001 for tricuspid annular plane systolic excursion vs LV global
      longitudinal strain), but a greater proportion of patients had LV dysfunction
      (30.8%) compared with RV dysfunction (6.2%) (P < .001). CONCLUSIONS: RV systolic
      function was impaired in LSs. The association between RV and LV function
      indicates a global, long-term cardiotoxic effect. However, RV dysfunction was
      less prevalent than LV dysfunction.

PMID- 27038516
TI  - Calcium channels contribute to albiflorin-mediated antinociceptive effects in
      mouse model.
AB  - Albiflorin (AF), one of important bioactive constituents of Paeonia lactiflora
      Radix, possesses neuro-protective effect. The present study aims to investigate
      the antinociceptive activities of AF and possible mechanisms. AF suppressed
      acetic acid-caused writhing, lengthened the latency period of mouse in hot plate
      test, and reduced the licking and biting response time of the injected mouse paw
      during phase I and phase II, and it suggested that AF exerted the antinociceptive
      activity mainly through central nervous system. Nimodipine, a commonly used
      calcium channels blocker, strongly lengthened AF-enhanced latency period of mouse
      in hot plate test. Compared with control group, AF reduced the levels of euronal
      nitric oxide synthase (nNOS), and enhanced the levels of serotonin (5-HT) in
      serum and/or hypothalamus before and after 30-s thermal stimuli. The reduced
      activation of calmodulin-dependent protein kinase II and c-Jun N-terminal kinase
      in hypothalamus was observed in AF-treated mice. Collectively, AF-mediated
      antinociceptive activities were, at least partially, related to calcium channels.

PMID- 27038517
TI  - Altered GABAA alpha5 subunit expression in the hypothalamic paraventricular
      nucleus of hypertensive and pregnant rats.
AB  - A characteristic of both hypertension and pregnancy is increased sympathetic
      nerve activity. The level of sympathetic activation is determined, in part, by a
      tonic GABAergic inhibition arising from the hypothalamic paraventricular nucleus
      (PVN). In hypertension, decreases in GABAergic inhibition and increases in
      glutamatergic excitation within the PVN contribute to this sympatho-excitation.
      In late-term pregnancy however, the sympatho-excitation appears to be mediated by
      decreases in GABAergic inhibition only. This study examined whether changes in
      subunit expression for GABAA receptors in the PVN could provide a molecular basis
      for the sympatho-excitation characteristic of hypertension and pregnancy.
      Hypertension and pregnancy were accompanied by significant decrease in the GABAA
      receptor alpha5 subunit in the PVN. We suggest that decreases in the alpha5
      subunit of the GABAA receptor may be important in mediating the sympatho
      excitation observed in both hypertension and pregnancy.

PMID- 27038518
TI  - The role of D-serine in peripheral tissues.
AB  - A considerable level of D-serine (a free D-amino acid) was discovered,
      surprisingly, in the mammalian brain in the early 1990s. Since then, D-serine has
      been considered to be a co-agonist of glutamate at the glycine site of NMDA
      receptors. D-serine is synthetized by racemization of L-serine in most neural and
      non-neural cells, and modulates a variety of physiological functions in mammals.
      In addition to the central nervous system, NMDA receptors have an important
      function in the modulation of physiological processes in peripheral tissues.
      Thus, investigations on the functions of D-serine in the peripheral nervous
      system, as well as the visceral organs, have gained attention in recent years. In
      this review we summarize the current knowledge on the role of D-serine in the
      kidneys, skeletal system, skin as well as on the non-adrenergic, non-cholinergic
      transmission within the autonomic nervous system. 

PMID- 27038519
TI  - Uvaol attenuates pleuritis and eosinophilic inflammation in ovalbumin-induced
      allergy in mice.
AB  - Uvaol, a triterpene present in olives and virgin olive oil, has been shown to
      possess anti-inflammatory properties and antioxidant effects. However, until now,
      no studies have demonstrated its potential effects on allergic inflammation. The
      aim of this study was to evaluate the anti-inflammatory effects of uvaol in a
      mouse model of allergy characterized by eosinophil-dominant inflammation in
      actively sensitized mice. The anti-inflammatory effect of uvaol was analyzed in
      two murine models of allergic inflammation (pleurisy and asthma). In these
      models, Swiss mice were sensitized and challenged with ovalbumin (OVA). In the
      pleurisy model, the pleural eosinophilic inflammation and IL-5 concentrations
      were examined 24h after the OVA challenge, while in the asthma model were
      examined the airway inflammation via bronchoalveolar lavage (BAL) fluid cytology
      and lung histopathology analyses. Our results showed that uvaol decreased the
      accumulation of eosinophils and the concentration of IL-5 in pleural effluent.
      Uvaol also demonstrated important anti-inflammatory activity by inhibiting
      production of IL-5 and influx of leukocytes, mainly of eosinophils, in BAL fluid,
      but without interfering with levels of reactive oxygen species in leukocytes.
      Moreover, the eosinophil infiltration, mucus production, number of alveoli that
      collapsed, and IL-5 levels in the lung were clearly decreased by uvaol treatment.
      These findings indicate that uvaol can be a good candidate for the treatment of
      allergic inflammation by inhibiting eosinophil influx and IL-5 production in
      ovalbumin-induced allergy. 

PMID- 27038520
TI  - The effect of the phenol compound ellagic acid on Ca(2+) homeostasis and
      cytotoxicity in liver cells.
AB  - Ellagic acid, a natural phenol compound found in numerous fruits and vegetables,
      causes various physiological effects in different cell models. However, the
      effect of this compound on Ca(2+) homeostasis in liver cells is unknown. This
      study examined the effect of ellagic acid on intracellular Ca(2+) concentration
      ([Ca(2+)]i) and established the relationship between Ca(2+) signaling and
      cytotoxicity in liver cells. The data show that ellagic acid induced
      concentration-dependent [Ca(2+)]i rises in HepG2 human hepatoma cells, but not in
      HA22T, HA59T human hepatoma cells or AML12 mouse hepatocytes. In HepG2 cells,
      this Ca(2+) signal response was reduced by removing extracellular Ca(2+) and was
      inhibited by store-operated Ca(2+) channel blockers (2-APB, econazole or
      SKF96365) and the protein kinase C (PKC) inhibitor GF109203X. In Ca(2+)-free
      medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor
      thapsigargin abolished ellagic acid-induced [Ca(2+)]i rises. Conversely,
      incubation with ellagic acid abolished thapsigargin-induced [Ca(2+)]i rises.
      Inhibition of phospholipase C (PLC) with U73122 also abolished ellagic acid
      induced [Ca(2+)]i rises. Ellagic acid (25-100MUM) concentration-dependently
      caused cytotoxicity in HepG2, HA22T or HA59T cells, but not in AML12 cells.
      Furthermore, this cytotoxic effect was partially prevented by prechelating
      cytosolic Ca(2+) with BAPTA-AM only in HepG2 cells. Together, in HepG2 cells,
      ellagic acid induced [Ca(2+)]i rises by inducing PLC-dependent Ca(2+) release
      from the endoplasmic reticulum and Ca(2+) entry via PKC-sensitive store-operated
      Ca(2+) channels. Moreover, ellagic acid induced Ca(2+)-associated cytotoxicity. 

PMID- 27038521
TI  - Reversal of morphine-induced respiratory depression by doxapram in anesthetized
      rats.
AB  - The present study was undertaken to investigate whether doxapram, a blocker of
      tandem pore K(+) (TASK-1/-3) channels, is a useful tool for recovery from
      morphine-induced ventilatory disturbances. Spontaneous ventilation and the hind
      leg withdrawal response against noxious thermal stimulation were recorded
      simultaneously in anesthetized rats. Morphine (1.0mg/kg, i.v.) decreased the
      minute volume resulting from depression of the ventilatory rate and tracheal
      airflow. Concomitantly, it prolonged the latency of withdrawal response against
      the thermal stimulation. Subsequent intravenous injection of doxapram recovered
      the morphine-induced ventilatory depression. This effect of doxapram declined
      rapidly after a single injection (1.0-3.0mg/kg, i.v.) but persisted with a
      continuous infusion (0.33mg/kg/min). Neither single injection nor continuous
      infusion of doxapram had any detectable effect on the analgesic potency of
      morphine. The central respiratory activity was recorded from the phrenic nerve in
      anesthetized, vagotomized, paralyzed and artificially ventilated rats. Morphine
      (3.0mg/kg, i.v.) induced respiratory depression, characterized by a prolonged
      plateau-like inspiratory discharge (apneustic discharge) in the phrenic nerve.
      Doxapram (10mg/kg, i.v.) restored the morphine-induced apneustic discharge to an
      augmenting inspiratory discharge. This study demonstrated that doxapram
      counteracted morphine-induced respiratory depression by stimulating the central
      respiratory network without compromising morphine antinociception. These results
      support the clinical use of doxapram for amelioration of ventilatory disturbances
      in patients treated with opioids. 

PMID- 27038522
TI  - Identification and characterization of heptapeptide modulators of the glycine
      receptor.
AB  - The glycine receptor is a member of the Cys-loop receptor superfamily of ligand
      gated ion channels and is implicated as a possible therapeutic target for the
      treatment of diseases such as alcoholism and inflammatory pain. In humans, four
      glycine receptor subtypes (alpha1, alpha2, alpha3, and beta) co-assemble to form
      pentameric channel proteins as either alpha homomers or alphabeta heteromers. To
      date, few agents have been identified that can selectively modulate the glycine
      receptor, especially those possessing subtype specificity. We used a cell-based
      method of phage display panning, coupled with two-electrode voltage-clamp
      electrophysiology in Xenopus laevis oocytes, to identify novel heptapeptide
      modulators of the alpha1beta glycine receptor. This involved a panning procedure
      in which the phage library initially underwent subtractive panning against Human
      Embryonic Kidney (HEK) 293 cells expressing alternative glycine receptor subtypes
      before panning the remaining library over HEK 293 cells expressing the target,
      the alpha1beta glycine receptor. Peptides were identified that act with
      selectivity on alpha1beta and alpha3beta, compared to alpha2beta, glycine
      receptors. In addition, peptide activity at the glycine receptor decreased when
      zinc was chelated by tricine, similar to previous observations of a decrease in
      ethanol's enhancing actions at the receptor in the absence of zinc. Comparisons
      of the amino acid sequences of heptapeptides capable of potentiating glycine
      receptor function revealed several consensus sequences that may be predictive of
      a peptide's enhancing ability. 

PMID- 27038524
TI  - Adaptation of an interim partial removable dental prosthesis as a radiographic
      template for implant placement.

PMID- 27038523
TI  - Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma
      xanthine oxidoreductase activity in db/db mice.
AB  - Topiroxostat, a xanthine oxidoreductase (XOR) inhibitor, has been shown to
      decrease the urinary albumin-to-creatinine ratio compared with placebo in
      hyperuricemic patients with stage 3 chronic kidney disease. Thus, we aimed to
      ascertain the albuminuria-lowering effect of topiroxostat in diabetic mouse.
      Db/db mice were fed standard diets with or without topiroxostat (0.1, 0.3, 1, and
      3mg/kg/day) and febuxostat (0.1, 0.3, and 1mg/kg/day) for four weeks. Urinary
      albumin and purine bodies levels, XOR activities, and drug concentrations in the
      liver, kidney, and plasma were measured. Moreover, the XOR inhibitory activity of
      each XOR inhibitor was evaluated with or without an exogenous protein in vitro.
      Topiroxostat decreased dose-dependently the urinary albumin excretion, but
      febuxostat did not show such a tendency. Treatment with topiroxostat inhibited
      plasma XOR activity with dose-dependent increase in plasma purine levels, which
      was not observed by febuxostat. Pharmacokinetic/pharmacodynamic analysis revealed
      that topiroxostat and febuxostat concentration in each tissue showed a good
      correlation with both the hypouricemic effect and plasma drug concentration,
      whereas the change in albuminuria correlated neither with the change in uric acid
      nor with drug concentration in plasma. However, the change in urinary albumin and
      plasma XOR activity showed good correlation in topiroxostat group. The 50%
      inhibitory concentration (IC50 value) of febuxostat against plasma XOR in vitro
      was 12-fold higher than that of topiroxostat, and increased by approximately 13
      fold by interfering with an exogenous protein. Topiroxostat caused reduced
      urinary albumin excretion, in which potent inhibition of the plasma XOR activity
      might be involved. 

PMID- 27038525
TI  - In vivo study of the effectiveness of quantitative percussion diagnostics as an
      indicator of the level of the structural pathology of teeth.
AB  - STATEMENT OF PROBLEM: Conventional dental diagnostic aids based upon imagery and
      patient symptoms are at best only partially effective for the detection of fine
      structural defects such as cracks in teeth. PURPOSE: The purpose of this clinical
      study was to determine whether quantitative percussion diagnostics (QPD) provided
      knowledge of the structural instability of teeth before restorative work begins.
      QPD is a mechanics-based methodology that tests the structural integrity of teeth
      noninvasively. MATERIAL AND METHODS: Eight human participants with 60 sites
      needing restoration were enrolled in an institutional review board-approved
      clinical study. Comprehensive examinations were performed in each human
      participant, including QPD testing. Each site was disassembled and
      microscopically video documented, and the results were recorded on a defect
      assessment sheet. Each restored site was then tested using QPD. The normal fit
      error (NFE), which corresponds to the localized defect severity, was correlated
      with any pretreatment structural pathology. RESULTS: QPD agreed with clinical
      disassembly in 55 of 60 comparisons (92% agreement). Moreover, the method
      achieved 98% specificity and 100% sensitivity for detecting structural
      pathologies found later upon clinical disassembly. Overall, the NFE was found to
      be highly predictive of advanced structural pathology. CONCLUSIONS: The data from
      the present in vivo study support the hypothesis that QPD can provide the
      clinician with advance knowledge of the structural instability of teeth before
      restorative work begins.

PMID- 27038526
TI  - Customized CAD-CAM healing abutment for delayed loaded implants.
AB  - When conventional prefabricated healing abutments are used, the surrounding soft
      tissue profile may be unfavorable at the time for restorative treatment,
      requiring additional time-consuming recontouring. This article presents a
      technique for fabricating a customized computer-aided design and computer-aided
      manufacturing (CAD-CAM) healing abutment for a delayed loaded dental implant
      placed in the region of a missing maxillary right first premolar. A surgical
      guide was fabricated and a definitive cast was made from the surgical guide. The
      cast was digitized using a scanner, and a customized healing abutment was
      digitally designed using computer software. The presented technique provides
      guided implant placement and predicts optimum soft tissue contours that enhance
      the implant emergence profile. 

PMID- 27038527
TI  - Three-dimensional evaluation of the reproducibility of presintered zirconia
      single copings fabricated with the subtractive method.
AB  - STATEMENT OF PROBLEM: Reproducibility is an important factor determining the
      success of a prosthesis. However, no studies have focused on identifying the
      location of errors on prostheses fabricated with the subtractive method, leading
      to a lack of standards for reproducibility evaluations. PURPOSE: The purpose of
      this in vitro study was to evaluate the reproducibility of the subtractive method
      by conducting 3-dimensional assessments of presintered single-tooth zirconia
      copings for different teeth. MATERIAL AND METHODS: Acrylic resin tooth molds for
      the canine (CAN), premolar (PRE), and molar (MOL) were used to prepare stone
      casts, and copings were designed and fabricated with the subtractive method. The
      intaglio surfaces of corresponding presintered zirconia copings were scanned with
      a blue light scanner. Initial scan data were used as a reference for comparisons
      with subsequent data for the measurement of errors. Nine color-difference maps
      were created for each of the 3 groups and used to calculate root-mean-square
      (RMS) error values. One-way analysis of variance and the Tukey honestly
      significant difference tests were used for statistical evaluations (alpha=.05).
      RESULTS: MOL copings exhibited the highest RMS error value (9.22 +/-1.56 MUm),
      which was significantly different from values for CAN (3.33 +/-2.65 MUm) and PRE
      (4.00 +/-2.40 MUm; P<.001) copings. Color-difference maps revealed maximum errors
      in the line angles. CONCLUSIONS: The highest reproducibility was observed for the
      CAN copings. The clinical reproducibility of the subtractive method can be
      improved by avoiding sharp angles during abutment preparation and careful
      reproduction of angles during prosthesis fabrication.

PMID- 27038528
TI  - Use of digital panoramic radiology in presurgical implant treatment planning to
      accurately assess bone density.
AB  - STATEMENT OF PROBLEM: No cost-effective method of ascertaining bone density from
      2-dimensional radiographic images is currently available for dental implants
      before surgery. PURPOSE: The purpose of this in vivo study was to use digital
      panoramic radiology and dental computed tomography (CT) to evaluate the bone
      density of specific points in the jaw near the tooth-bearing areas. The objective
      was to determine whether digital panoramic radiology can be used in assessing
      bone density as an alternative to a more expensive and complex dental CT.
      MATERIAL AND METHODS: This study involved determining bone densities at
      predetermined anatomic landmarks near tooth-bearing areas of the jaws of 20
      participants, using digital panoramic radiology in gray-level scale with a lead
      step wedge. Subsequently, the bone densities of the same points were determined
      in Hounsfield units (Hu) with dental CT. The data collected after interpretation
      of the panoramic radiograph and CT were tabulated and analyzed statistically.
      RESULTS: Bone density measured using CT correlated with the first 3 steps of (A,
      B, and C) the digital scale of gray. Further analysis conducted using the Mann
      Whitney U test showed a significant association between step A to detect D4 bone,
      step B to detect D3 bone, and step C to detect D2 type bone. CONCLUSIONS: The
      digital scale of gray obtained from a lead step wedge can be effectively used
      with digital orthopanoramic radiology to assess bone density before the placement
      of implants, but with certain restrictions.

PMID- 27038529
TI  - Use of ceria-stabilized zirconia/alumina nanocomposite for fabricating the
      frameworks of removable dental prostheses: A clinical report.
AB  - Ceria-stabilized zirconia/alumina nanocomposite (Ce-TZP/A) exhibits an elasticity
      equivalent to that of cobalt-chromium alloy and a flexural property that is
      superior to that of yttria-tetragonal zirconia polycrystal. Therefore, the use of
      Ce-TZP/A for the fabrication of removable dental prosthesis frameworks is being
      studied. However, the current English literature does not include any clinical
      report on the use of Ce-TZP/A for the fabrication of the entire framework. This
      clinical report describes the process and outcomes of fabricating a mandibular
      implant-supported overdenture and a maxillary complete denture with Ce-TZP/A as
      the framework material. 

PMID- 27038530
TI  - Does vitamin D supplementation alter plasma adipokines concentrations? A
      systematic review and meta-analysis of randomized controlled trials.
AB  - We aimed to elucidate the role of vitamin D supplementation on adipokines through
      a systematic review and a meta-analysis of randomized placebo-controlled trials
      (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar
      through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta
      analysis of data from 7 studies did not find a significant change in plasma
      adiponectin concentrations following vitamin D supplementation (mean difference
      [MD]: 4.45%, 95%CI: -3.04, 11.93, p=0.244; Q=2.18, I(2)=0%). In meta-regression,
      changes in plasma adiponectin concentrations following vitamin D supplementation
      were found to be independent of treatment duration (slope: 0.25; 95%CI: -0.69,
      1.19; p=0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope:
      -0.02; 95%CI: -0.15, 0.12; p=0.780). Meta-analysis of data from 6 studies did not
      find a significant change in plasma leptin concentrations following vitamin D
      supplementation (MD: -4.51%, 95%CI: -25.13, 16.11, p=0.668; Q=6.41, I(2)=21.97%).
      Sensitivity analysis showed that this effect size is sensitive to one of the
      studies; removing it resulted in a significant reduction in plasma leptin levels
      (MD: -12.81%, 95%CI: -24.33, -1.30, p=0.029). In meta-regression, changes in
      plasma leptin concentrations following vitamin D supplementation were found to be
      independent of treatment duration (slope: -1.93; 95%CI: -4.08, 0.23; p=0.080).
      However, changes in serum 25(OH)D were found to be significantly associated with
      changes in plasma leptin levels following vitamin D supplementation (slope: 1.05;
      95%CI: 0.08, 2.02; p=0.033). In conclusion, current data did not indicate a
      significant effect of vitamin D supplementation on adiponectin and leptin levels.

PMID- 27038531
TI  - The water soluble ruthenium(II) organometallic compound [Ru(p-cymene)(bis(3,5
      dimethylpyrazol-1-yl)methane)Cl]Cl suppresses triple negative breast cancer
      growth by inhibiting tumor infiltration of regulatory T cells.
AB  - Ruthenium compounds have become promising alternatives to platinum drugs by
      displaying specific activities against different cancers and favorable toxicity
      and clearance properties. Here, we show that the ruthenium(II) complex [Ru(p
      cymene)(bis(3,5-dimethylpyrazol-1-yl)methane)Cl]Cl (UNICAM-1) exhibits potent in
      vivo antitumor effects. When administered as four-dose course, by repeating a
      single dose (52.4mgkg-1) every three days, UNICAM-1 significantly reduces the
      growth of A17 triple negative breast cancer cells transplanted into FVB syngeneic
      mice. Pharmacokinetic studies indicate that UNICAM-1 is rapidly eliminated from
      kidney, liver and bloodstream thanks to its high hydrosolubility, exerting
      excellent therapeutic activity with minimal side effects. Immunohistological
      analysis revealed that the efficacy of UNICAM-1, mainly relies on its capacity to
      reverse tumor-associated immune suppression by significantly reducing the number
      of tumor-infiltrating regulatory T cells. Therefore, UNICAM-1 appears very
      promising for the treatment of TNBC.

PMID- 27038532
TI  - Effect of recombinant plasminogen activator timing on thrombolysis in a novel rat
      embolic stroke model.
AB  - The treatment of acute ischemic stroke (AIS) using thrombolysis with recombinant
      tissue-plasminogen activator (rtPA, alteplase) is limited by its narrow time
      window and the risk of hemorrhage. Recombinant plasminogen activator (rPA,
      reteplase) has been used clinically on coronary artery thrombosis and acute
      myocardial infarction. It is necessary to induce strokes experimentally as a
      means of validating the rPA timing on patients with AIS. However, current embolic
      models cannot mimic clinical situations well due to the embolus's composition of
      dried blood clots or artificial materials. In this paper, we used two novel rat
      thromboembolic models to determine the dosage-effect relationship and therapeutic
      time window of r-PA. Male rats were administered rPA or rtPA intravenously at 2
      12h postischemia. Cerebral blood flow, behavioral outcomes and infarct volume
      within the same animal group were determined. Our results demonstrated that rPA
      (0.2 and 0.4mg/kg) or rtPA (0.2mg/kg) restored focal perfusion, reduced cerebral
      infarction, and improved behavioral outcomes at 2-4h postischemia. rPA but not
      rtPA significantly restored focal perfusion at 6h postischemia. However, delayed
      rPA-treatment neither decreased infarct volume nor improved the neurological
      disorder. Cerebral hemorrhage occurred at 6h postischemia detected by Evan's blue
      leakage and tissue hemoglobin content. Collectively, Thrombolysis with rPA may be
      beneficial in revascularization at an acceptable dosage of 0.2-0.4mg/kg within 6h
      after the cerebral infarct onset.

PMID- 27038533
TI  - Anthocyanins in cardioprotection: A path through mitochondria.
AB  - Constantly growing experimental data from in vitro, in vivo and epidemiological
      studies show the great potential of anthocyanin-containing fruit and berry
      extracts or pure individual anthocyanins as cardioprotective food components or
      pharmacological compounds. In general it is regarded that the cardioprotective
      activity of anthocyanins is related to their antioxidant properties. However
      there are recent reports that certain anthocyanins may protect the heart against
      ischemia/reperfusion-induced injury by activating signal transduction pathways
      and sustaining mitochondrial functions instead of acting solely as antioxidants.
      In this review, we summarize the proposed mechanisms of direct or indirect
      actions of anthocyanins within cardiac cells with the special emphasis on
      recently discovered their pharmacological effects on mitochondria in
      cardioprotection: reduction of cytosolic cytochrome c preventing apoptosis and
      sustainment of electron transfer between NADH dehydrogenase and cytochrome c
      supporting oxidative phosphorylation in ischemia-damaged mitochondria.

PMID- 27038534
TI  - Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset
      treatable metabolic disease.
AB  - INTRODUCTION: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a
      rare, treatable, beta-oxidation disorder responsible for neuromuscular symptoms
      in adults. This case series describes the clinical and biochemical features of 13
      French patients with late-onset MADD. METHODS AND RESULTS: Thirteen ambulant
      patients (eight women, five men), with a median age at onset of 27 years,
      initially experienced exercise intolerance (n=9), isolated muscle weakness (n=1)
      and a multisystemic pattern with either central nervous system or hepatic
      dysfunction (n=3). During the worsening period, moderate rhabdomyolysis (n=5), a
      pseudomyasthenic pattern (n=5) and acute respiratory failure (n=1) have been
      observed. Weakness typically affected the proximal limbs and axial muscles, and
      there was sometimes facial asymmetry (n=3). Moderate respiratory insufficiency
      was noted in one case. Median baseline creatine kinase was 190IU/L. Lactacidemia
      was sometimes moderately increased at rest (3/10) and after exercise (1/3). The
      acylcarnitine profile was characteristic, with increases in all chain-length
      acylcarnitine species. Electromyography revealed a myogenic pattern, while muscle
      biopsy showed lipidosis, sometimes with COX-negative fibers (n=2). The
      mitochondrial respiratory chain was impaired in five cases, with coenzyme Q10
      decreased in two cases. All patients harbored mutations in the ETFDH gene (four
      homozygous, seven compound heterozygous, two single heterozygous), with nine
      previously unidentified mutations. All patients were good responders to medical
      treatment, but exercise intolerance and/or muscular weakness persisted in 11 of
      them. CONCLUSION: Late-onset forms of MADD may present as atypical beta-oxidation
      disorders. Acylcarnitine profiling and muscle biopsy remain the most decisive
      investigations for assessing the diagnosis. These tests should thus probably be
      performed more widely, particularly in unexplained cases of neuromuscular and
      multisystemic disorders.

PMID- 27038535
TI  - Care pathways and healthcare use of stroke survivors six months after admission
      to an acute-care hospital in France in 2012.
AB  - INTRODUCTION: Care pathways and healthcare management are not well described for
      patients hospitalized for stroke. METHODS: Among the 51 million beneficiaries of
      the French national health insurance general scheme (77% of the French
      population), patients hospitalized for a first stroke in 2012 and still alive six
      months after discharge were included using data from the national health
      insurance information system (Sniiram). Patient characteristics were described by
      discharge destination-home or rehabilitation center (for < 3 months)-and were
      followed during their first three months back home. RESULTS: A total of 61,055
      patients had a first admission to a public or private hospital for stroke (mean
      age; 72 years, 52% female), 13% died during their stay and 37% were admitted to a
      stroke management unit. Overall, 40,981 patients were still alive at six months:
      33% of them were admitted to a rehabilitation center (mean age: 73 years) and 54%
      were discharged directly to their home (mean age 67 years). For each group, 45
      and 62% had been previously admitted to a stroke unit. Patients discharged to
      rehabilitation centers had more often comorbidities, 39% were highly physically
      dependent and 44% were managed in specialized neurology centers. For patients
      with a cerebral infarction who were directly discharged to their home 76%
      received at least one antihypertensive drug, 96% an antithrombotic drug and 76% a
      lipid-lowering drug during the following month. For those with a cerebral
      hemorrhage, these frequencies were respectively 46, 33 and 28%. For those
      admitted to a rehabilitation center, more than half had at least one visit with a
      physiotherapist or a nurse, 15% a speech therapist, 10% a neurologist or a
      cardiologist and 15% a psychiatrist during the following three months back home
      (average numbers of visits for those with at least one visit: 23 for
      physiotherapists and 100 for nurses). Patients who returned directly back home
      had fewer physiotherapist (30%) or nurse (47%) visits but more medical
      consultations. The 3-month re-hospitalization rate for patients who were
      discharged directly to their home was 23% for those who had been admitted to a
      stroke unit and 25% for the others. In rehabilitation centers, this rate was 10%
      for patients who stayed < 3 months. CONCLUSIONS: These results illustrate the
      value of administrative databases to study stroke management, care pathways and
      ambulatory care. These data should be used to improve care pathways,
      organization, discharge planning and treatments.

PMID- 27038536
TI  - [Optic disc drusen in children: Advantages of various imaging modalities].
AB  - In children, optic disc drusen pose a diagnostic problem with papilledema when
      they are buried. The goal of our study is to retrospectively compare the results
      of examinations performed in 34 children with optic disc drusen. In children who
      underwent ultrasonography and autofluorescence imaging, the results were
      conclusive in both examinations in 44.7% of cases, and in neither of the two
      examinations in 27.6% of cases. Ultrasonography alone demonstrated superiority in
      diagnosing 27.6% of eyes, whereas autofluorescence imaging was inconclusive.
      Since diagnostic confusion with papilledema persisted in seven children,
      angiography was performed. B-mode ultrasonography constitutes a relevant
      examination in the diagnosis of buried optic disc drusen in children and shows
      superiority in our study compared to autofluorescence imaging. 

PMID- 27038537
TI  - [Spontaneously regressed retinoblastoma].

PMID- 27038538
TI  - Performance of an antigen assay for diagnosing acute hepatitis E virus genotype 3
      infection.
AB  - BACKGROUND: Hepatitis E virus (HEV) is a major cause of hepatitis worldwide. Its
      diagnosis is based on the detection of anti-HEV IgM and/or HEV-RNA. OBJECTIVE: To
      evaluate the performance of the Wantai HEV-antigen (Ag) ELISA(Plus) assay for
      diagnosing acute HEV infections. STUDY DESIGN: Specificity was assessed using 100
      blood samples containing no anti-HEV IgM, anti-HEV IgG, or HEV-RNA. Cross
      reactivity was assessed using samples positive for hepatitis C virus RNA (n=10),
      Epstein-Barr virus DNA (n=10) and cytomegalovirus DNA (n=10). Serial dilutions of
      4 HEV RNA positive samples were used to estimate the corresponding viremia
      detected with the Ag assay. Blood samples from 33 immunocompetent and 31
      immunocompromised patients with an acute HEV genotype 3 infection, HEV-RNA
      positive, were tested to assess diagnostic sensitivity. RESULTS: The HEV-Ag assay
      was 100% specific, with no cross-reactivity. The lower viremias detected ranged
      from 10(3)copies/ml to 10(5)copies/ml (800-80,000UI/ml). Diagnostic sensitivity
      for an acute HEV infection was 91%, with no significant difference between
      immunocompetent (88%) and immunocompromised (94%) patients. The HEV-Ag assay was
      more frequently positive in immunocompromised patients at the acute phase (94%)
      than was the anti-HEV IgM test (71%; p=0.04). The HEV-Ag assay ratio was
      correlated with HEV-RNA viral load (rho=0.54; p<0.0001). CONCLUSION: The HEV-Ag
      assay performed well and could be suitable for laboratories with no molecular
      diagnosic facilities.

PMID- 27038539
TI  - Bilosomes in the context of oral immunization: development, challenges and
      opportunities.
AB  - Oral administration remains the most favored means of drug administration as far
      as patient compliance is concerned. For the majority of vaccines and biologics,
      the oral route is not a good choice because of diminished uptake of the
      administered dose. Vesicular carriers like liposomes and niosomes are among the
      potential candidates for vaccine delivery by the oral route but their instability
      in the gastrointestinal environment is a problem. Bilosomes represent a key
      advance in oral vaccine delivery because they are more resistant to disruption by
      gastric acid as well as enzymes. Here, we focus on different aspects of bilosomes
      including composition, developmental techniques, stability, transitional
      modifications and scale-up - emphasizing their biomedical potential in oral
      immunization against various diseases.

PMID- 27038540
TI  - Bilateral polypoidal choroidal vasculopathy coexisting with exudative and
      atrophic age-related macular degeneration.
AB  - OBJECTIVE: To present the case of simultaneous presentation of polypoidal
      choroidal vasculopathy (PCV) and aged-related macular degeneration (AMD). CASE
      REPORT: An 83-year-old woman presented with decreased vision in the left eye
      (LE). In the examination there was an orange peripapillary lesion surrounded by
      lipid exudates and another subfoveal greyish lesion in the LE. Disciform scarring
      was observed in the right eye. Fluorescein angiography showed a classic
      neovascular membrane in in the LE fovea. Indocyanine angiography (ICGA) showed a
      polyp-like peri-papillary aneurysmal dilation in both eyes. The patient was
      treated with photodynamic therapy and anti-VEFG injections with stabilisation of
      the lesions. CONCLUSION: PCV and AMD can co-exist in unusual cases. When PCV is
      suspected, ICGA is mandatory for diagnosis.

PMID- 27038541
TI  - Printable low-cost, sustained and dynamic cell stretching apparatus.
AB  - Deformations that are applied on body tissues during daily activities, as a
      result of morbid conditions, or during various medical treatments, affect cell
      viability and biological function. Such mechanobiological phenomena are often
      studied in vitro, in monolayer cultures. To facilitate such studies cost
      effectively, we have developed a novel, printable cell stretching apparatus. The
      apparatus is used to apply tensile strains on cells cultured on elastic,
      stretchable substrata, either by sustained or by dynamic-cyclic application. Most
      of the apparatus parts are three-dimensionally printed (excluding motors), and
      stretching is automatically performed by two direct current geared motors that
      are controlled by a programmable microcontroller platform. To demonstrate
      functionality of this novel printable device, which can be produced in multiple
      copies in research labs at a cost of under 100 US$ per unit, including motors and
      controller, we performed cell culture studies monitored by fluorescence
      microscopy. Specifically, we have applied sustained and cyclic, radial stretching
      at large strains to NIH3T3 mouse fibroblasts, and have demonstrated that cell
      viability, adhesion and morphology were maintained following stretching. Our
      apparatus is designed to be low-cost, rapidly manufactured at a university or
      small-company setting, and simple to use and control, where its flexible,
      versatile design allows users to experimentally induce different stretching
      regimes with varying amplitudes and frequencies.

PMID- 27038542
TI  - The development and validation of using inertial sensors to monitor postural
      change in resistance exercise.
AB  - This research presented and validated a method of assessing postural changes
      during resistance exercise using inertial sensors. A simple lifting task was
      broken down to a series of well-defined tasks, which could be examined and
      measured in a controlled environment. The purpose of this research was to
      determine whether timing measures obtained from inertial sensor accelerometer
      outputs are able to provide accurate, quantifiable information of resistance
      exercise movement patterns. The aim was to complete a timing measure validation
      of inertial sensor outputs. Eleven participants completed five repetitions of 15
      different deadlift variations. Participants were monitored with inertial sensors
      and an infrared three dimensional motion capture system. Validation was
      undertaken using a Will Hopkins Typical Error of the Estimate, with a Pearson's
      correlation and a Bland Altman Limits of Agreement analysis. Statistical
      validation measured the timing agreement during deadlifts, from inertial sensor
      outputs and the motion capture system. Timing validation results demonstrated a
      Pearson's correlation of 0.9997, with trivial standardised error (0.026) and
      standardised bias (0.002). Inertial sensors can now be used in practical settings
      with as much confidence as motion capture systems, for accelerometer timing
      measurements of resistance exercise. This research provides foundations for
      inertial sensors to be applied for qualitative activity recognition of resistance
      exercise and safe lifting practices.

PMID- 27038543
TI  - Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2
      signaling pathway in K562/Adr human leukemia cells.
AB  - Drug resistance limits leukemia treatment and chaetominine, a cytotoxic alkaloid
      that promotes apoptosis in a K562 human leukemia cell line via the mitochondrial
      pathway was studied with respect to chemoresistance in a K562/Adr human resistant
      leukemia cell line. Cytotoxicity assays indicated that K562/Adr resistance to
      adriamycin (ADR) did not occur in the presence of chaetominine and that
      chaetominine increased chemosensitivity of K562/Adr to ADR. Data show that
      chaetominine enhanced ADR-induced apoptosis and intracellular ADR accumulation in
      K562/Adr cells. Accordingly, chaetominine induced apoptosis by upregulating ROS,
      pro-apoptotic Bax and downregulating anti-apoptotic Bcl-2. RT-PCR and western
      blot confirmed that chaetominine suppressed highly expressed MRP1 at mRNA and
      protein levels. But little obvious alternation of another drug transporter MDR1
      mRNA was observed. Furthermore, inhibition of MRP1 by chaetominine relied on
      inhibiting Akt phosphorylation and nuclear Nrf2. In summary, chaetominine
      strongly reverses drug resistance by interfering with the PI3K/Akt/Nrf2
      signaling, resulting in reduction of MRP1-mediated drug efflux and induction of
      Bax/Bcl-2-dependent apoptosis in an ADR-resistant K562/Adr leukemia cell line.

PMID- 27038544
TI  - Structural characterization of the full-length response regulator spr1814 in
      complex with a phosphate analogue reveals a novel conformational plasticity of
      the linker region.
AB  - Spr1814 of Streptococcus pneumoniae is a response regulator (RR) that belongs to
      the NarL/FixJ subfamily and has a four-helix helix-turn-helix DNA-binding domain.
      Here, the X-ray crystal structure of the full-length spr1814 in complex with a
      phosphate analogue beryllium fluoride (BeF3(-)) was determined at 2.0 A. This
      allows for a structural comparison with the previously reported full-length
      unphosphorylated spr1814. The phosphorylation of conserved aspartic acid residue
      of N-terminal receiver domain triggers a structural perturbation at the alpha4
      beta5-alpha5 interface, leading to the domain reorganization of spr1814, and this
      is achieved by a rotational change in the C-terminal DNA-binding domain. 

PMID- 27038545
TI  - Collagencin, an antibacterial peptide from fish collagen: Activity, structure and
      interaction dynamics with membrane.
AB  - In this study, we first report characterization of collagencin, an antimicrobial
      peptide identified from fish collagen hydrolysate. The peptide completely
      inhibited the growth of Staphylococcus aureus at 1.88 mM. Although non-toxic up
      to 470 MUM, collagencin was hemolytic at higher concentrations. The secondary
      structure of collagencin was mainly composed by beta-sheet and beta-turn as
      determined by CD measurements and molecular dynamics. The peptide is likely to
      form beta-sheet structure under hydrophobic environments and interacts with both
      anionic (phosphatidylglycerol) and zwitterionic (phosphoethanolamine and
      phosphatidylcholine) lipids as shown with CD spectroscopy and molecular dynamics.
      The peptide formed several hydrogen bonds with both POPG and POPE lipids and
      remained at membrane-water interface, suggesting that collagencin antibacterial
      action follows a carpet mechanism. Collagenous fish wastes could be processed by
      enzymatic hydrolysis and transformed into products of high value having
      functional or biological properties. Marine collagens are a promising source of
      antimicrobial peptides with new implications in food safety and human health. 

PMID- 27038546
TI  - CD147 promotes the formation of functional osteoclasts through NFATc1 signalling.
AB  - CD147, a membrane glycoprotein of the immunoglobulin superfamily, is highly
      upregulated during dynamic cellular events including tissue remodelling. Elevated
      CD147 expression is present in the joint of rheumatoid arthritis patients.
      However, the role of CD147 in bone destruction remains unclear. To determine
      whether CD147 is involved in osteoclastogenesis, we studied its expression in
      mouse osteoclasts and its role in osteoclast differentiation and function. CD147
      expression was markedly upregulated during osteoclast differentiation. To
      investigate the role of CD147 in receptor activator of nuclear factor-kappa B
      ligand (RANKL)-induced osteoclastogenesis and bone resorption activity,
      osteoclast precursor cells were transfected with CD147 siRNA. Decreased CD147
      expression inhibited osteoclast formation and bone resorption, inhibited RANKL
      induced nuclear translocation of the nuclear factor of activated T cells (NFAT)
      c1 and decreased the expression of the d2 isoform of vacuolar ATPase Vo domain
      and cathepsin K. Therefore, CD147 plays a critical role in the differentiation
      and function of osteoclasts by upregulating NFATc1 through the autoamplification
      of its expression in osteoclastogenesis. 

PMID- 27038547
TI  - MiRNA-199a-5p influences pulmonary artery hypertension via downregulating Smad3.
AB  - MicroRNAs (miRNAs) play important roles in pulmonary artery hypertension (PAH).
      Recently, it has been reported that miR-199a-5p participates in the progression
      of chronic obstructive pulmonary disease, ventricular hypertrophy and heart
      failure. However, the roles of miR-199a-5p in PAH are still unclear. In the
      present study, miR-199a-5p was investigated in PAH rat models and in human
      pulmonary artery smooth muscle cells (HPASMCs) and endothelial cells (HPAECs).
      The expression of miR-199a-5p was significantly increased following PAH
      induction, and anti-miR-199a-5p could increase the nitric oxide (NO) level and
      decrease the PAH-induced upregulation of pulmonary artery pressure and right
      ventricular hypertrophy. Moreover, in HPASMCs and HPAECs, miR-199a-5p
      overexpression could inhibit the level of NO and promote the concentration of
      Ca(2+), but anti-miR-199a-5p showed opposite results. Further analysis
      demonstrated that miR-199a-5p attenuated the expression of Smad3. Importantly,
      Smad3 was confirmed to be the target gene of miR-199a-5p using dual-luciferase
      reporter assay. Mechanism analyses revealed that the downregulation of NO and the
      upregulation of Ca(2+) caused by miR-199a-5p were all reversed by Smad3
      overexpression in HPASMCs and HPAECs. Moreover, in PAH model, Smad3, p-Smad3 and
      Smad4 were all downregulated in lung tissues, and SIS3 (Smad3 inhibitor) could
      reverse the effects of anti-miR-199a-5p in PAH rats. Our date suggest that miR
      199a-5p may function as a regulator of PAH by targeting Smad3, indicating a novel
      therapeutic strategy for patients with PAH.

PMID- 27038548
TI  - Asymmetric reduction of acetophenone into R-(+)-1-phenylethanol by endophytic
      fungus Neofusicoccum parvum BYEF07 isolated from Illicium verum.
AB  - Seventy-nine strains of endophytic fungi isolated from the healthy leaves, twigs
      and fruits of Illicium verum were screened for the asymmetric reduction
      activities to acetophenone. Strain BYEF07, which showed relatively high reduction
      activities, has been classified as Neofusicoccum parvum, and the main product was
      confirmed to be (R)-(+)-1-phenylethanol by GC-MS and chiral HPLC methods. The bio
      reduction conditions of acetophenone by cells of N. parvum BYEF07 were
      investigated in detail. Under the conditions of 1.8 g/L of acetophenone, 100 g/L
      of microorganism cells and 10 g/L of glucose in 40 mL Na2HPO4 KH2PO4 buffer
      solution at pH7.5, 30  degrees C and 150 rpm, after 48 h reaction, the production
      yield of 1-phenylethanol and enantiomeric excess value of (R)-(+)-1-phenylethanol
      were 78% and 96%, respectively.

PMID- 27038549
TI  - Generation of transcriptome profiling and gene functional analysis in Gossypium
      hirsutum upon Verticillium dahliae infection.
AB  - Verticillium wilt caused by the soil-borne fungus Verticillium dahliae, is a
      devastating disease in cotton. To get more candidate genes related to wilt
      resistance, a normalized, full-length cDNA library was used to generate the
      transcriptome profile from a wilt-resistant Gossypium hirsutum variety
      (Zhongzhimian KV3) upon V. dahliae strain V991 infection. Total 3486 high-quality
      ESTs were focused from randomly selected 4000 clones, which included 3065
      singletons and 421 contigs. To categorize these unigenes, they were compared to
      functional domain databases. Total 106 unigenes were found to be homologous to
      known defense-related genes. Among them, PR genes were the major group.
      Furthermore, knockdown of GhWRKY22, GhWRKY33, GhChitinase, GhCML, and GhDirigent
      resulted in increased susceptibility of resistant cotton to V. dahliae infection.
      The results of transcriptome profiles and virus induced gene silencing (VIGS)
      analysis laid a good foundation for further investigation of cotton resistance to
      wilt disease.

PMID- 27038551
TI  - Oncogenic epigenetic control.

PMID- 27038550
TI  - Establishing moderators and biosignatures of antidepressant response in clinical
      care (EMBARC): Rationale and design.
AB  - Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for
      any given antidepressant. No biological or clinical marker has demonstrated
      sufficient ability to match individuals to efficacious treatment. Biosignatures
      developed from the systematic exploration of multiple biological markers, which
      optimize treatment selection for individuals (moderators) and provide early
      indication of ultimate treatment response (mediators) are needed. The rationale
      and design of a multi-site, placebo-controlled randomized clinical trial of
      sertraline examining moderators and mediators of treatment response is described.
      The target sample is 300 participants with early onset (<=30 years) recurrent
      MDD. Non-responders to an 8-week trial are switched double blind to either
      bupropion (for sertraline non-responders) or sertraline (for placebo non
      responders) for an additional 8 weeks. Clinical moderators include anxious
      depression, early trauma, gender, melancholic and atypical depression, anger
      attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression.
      Biological moderator and mediators include cerebral cortical thickness, task
      based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor
      imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG),
      cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline
      and week 1, except DTI, assessed only at baseline. The study is designed to
      standardize assessment of biomarkers across multiple sites as well as institute
      replicable quality control methods, and to use advanced data analytic methods to
      integrate these markers. A Differential Depression Treatment Response Index
      (DTRI) will be developed. The data, including biological samples (DNA, RNA, and
      plasma collected before and during treatment), will become available in a public
      scientific repository. CLINICAL TRIAL REGISTRATION: Establishing Moderators and
      Biosignatures of Antidepressant Response for Clinical Care for Depression
      (EMBARC). Identifier: NCT01407094. URL:
      http://clinicaltrials.gov/show/NCT01407094.

PMID- 27038553
TI  - Oxaliplatin-Induced Neuropathy: A Long-Term Clinical and Neurophysiologic Follow
      Up Study.
AB  - BACKGROUND: Oxaliplatin is an effective drug used mainly for advanced colorectal
      cancer. Neurotoxicity is the major side effect of oxaliplatin. The present
      clinical and neurophysiologic study was conducted to evaluate patients receiving
      oxaliplatin therapy. PATIENTS AND METHODS: Thirty-one consecutive patients with
      colorectal cancer who received oxaliplatin therapy were followed up for more than
      3 years. The patients underwent clinical and neurophysiologic tests for large and
      small fiber function at every visit. RESULTS: Most of the patients received
      oxaliplatin-based chemotherapy at the initial dose of 130 mg/m(2) for 6 to 8
      cycles, normally every 3 weeks. Acute neurotoxicity with cold and mechanical
      hyperalgesia was reported by the vast majority of patients after each cycle of
      therapy and was confirmed by the quantitative sensory, filament, and axon reflex
      test. Chronic sensory cumulative neuropathy developed in most of the patients
      after the middle of therapy with numbness and was assessed using clinical scales,
      nerve conduction studies, and the vibration threshold. Our results support the
      persistence of the sensory nerve deficits for years after cessation of
      oxaliplatin therapy. CONCLUSION: Our study has confirmed the results of a few
      previous long-term studies concerning the persistence of chronic large sensory
      fiber neuropathy and the influence of the cumulative dose of oxaliplatin on the
      development and severity of the chronic neuropathy. Our findings have improved
      the knowledge about the acute oxaliplatin-induced neurotoxicity using the C-fiber
      axon reflex response.

PMID- 27038552
TI  - IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in
      oral squamous cell carcinoma.
AB  - Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators
      of the Janus kinase/signal transducer and activator of transcription (JAK/STAT)
      pathway. Dysregulation of SOCS protein expression in cancers can be one of the
      mechanisms that maintain STAT activation, but this mechanism is still poorly
      understood in oral squamous cell carcinoma (OSCC). Here, we report that SOCS2
      protein is significantly downregulated in OSCC patients and its levels are
      inversely correlated with miR-424-5p expression. We identified the SOCS2 protein,
      which modulates STAT5 activity, as a direct target of miR-424-5p. The miR-424-5p
      induced STAT5 phosphorylation, matrix metalloproteinases (MMPs) expression, and
      cell migration and invasion were blocked by SOCS2 restoration, suggesting that
      miR-424-5p exhibits its oncogenic activity through negatively regulating SOCS2
      levels. Furthermore, miR-424-5p expression could be induced by the cytokine IL-8
      primarily through enhancing STAT5 transcriptional activity rather than NF-kappaB
      signaling. Antagomir-mediated inactivation of miR-424-5p prevented the IL-8
      induced cell migration and invasion, indicating that miR-424-5p is required for
      IL-8-induced cellular invasiveness. Taken together, these data indicate that
      STAT5-dependent expression of miR-424-5p plays an important role in mediating IL
      8/STAT5/SOCS2 feedback loop, and scavenging miR-424-5p function using antagomir
      may have therapeutic potential for the treatment of OSCC.

PMID- 27038554
TI  - [Keep an eye on transient ischaemic attacks in patients treated with eyedrops].

PMID- 27038555
TI  - Circulating pattern and genomic characteristics of influenza B viruses in Taiwan
      from 2003 to 2014.
AB  - BACKGROUND/PURPOSE: Influenza B viruses are antigenically classified into
      Yamagata and Victoria lineages according to their hemagglutinin (HA) proteins.
      These two lineages are known to either appear sequentially or cocirculate in
      Taiwan. METHODS: Taiwanese influenza B viral HA and neuraminidase (NA) sequences
      between 2003 and 2014 were determined and analyzed. A time-scaled phylogenetic
      tree was constructed to decipher the evolutionary trends of these sequences, and
      the reassortment between the two lineages. Positively selected amino acids were
      predicted, demonstrating the adaptive mutations of the circulating pattern.
      RESULTS: The HA phylogenetic tree revealed that the Victoria lineage evolved into
      a ladder-like pattern, whereas the Yamagata lineage exhibited complex topology
      with several independently evolved clades on which viruses from different
      influenza seasons interlaced. For several seasons, HA sequences were found to be
      dominated by strains of the same lineage as the corresponding vaccine strain.
      Inspecting these sequences revealed that frequent mutations occurred in
      neutralizing epitopes and glycosylation sites. Amino acid positions 212 and 214
      of N-glycosylation sites, which are known to be critical determinants of receptor
      binding specificity, were found to be subject to positive selection. No drug
      resistant sites were noticed in the NA sequences. In addition, we identified
      several cases of NA reassortment with an overall incidence rate of 6% for the
      investigated Taiwan strains. CONCLUSION: We highlighted the interplay between
      mutations in the glycosylation sites and epitope during HA evolution. These are
      crucial molecular signatures to be monitored for influenza B epidemics in the
      future.

PMID- 27038556
TI  - De novo assembly and characterization of the Trichuris trichiura adult worm
      transcriptome using Ion Torrent sequencing.
AB  - Infection with helminthic parasites, including the soil-transmitted helminth
      Trichuris trichiura (human whipworm), has been shown to modulate host immune
      responses and, consequently, to have an impact on the development and
      manifestation of chronic human inflammatory diseases. De novo derivation of
      helminth proteomes from sequencing of transcriptomes will provide valuable data
      to aid identification of parasite proteins that could be evaluated as potential
      immunotherapeutic molecules in near future. Herein, we characterized the
      transcriptome of the adult stage of the human whipworm T. trichiura, using next
      generation sequencing technology and a de novo assembly strategy. Nearly 17.6
      million high-quality clean reads were assembled into 6414 contiguous sequences,
      with an N50 of 1606bp. In total, 5673 protein-encoding sequences were
      confidentially identified in the T. trichiura adult worm transcriptome; of these,
      1013 sequences represent potential newly discovered proteins for the species,
      most of which presenting orthologs already annotated in the related species T.
      suis. A number of transcripts representing probable novel non-coding transcripts
      for the species T. trichiura were also identified. Among the most abundant
      transcripts, we found sequences that code for proteins involved in lipid
      transport, such as vitellogenins, and several chitin-binding proteins. Through a
      cross-species expression analysis of gene orthologs shared by T. trichiura and
      the closely related parasites T. suis and T. muris it was possible to find twenty
      six protein-encoding genes that are consistently highly expressed in the adult
      stages of the three helminth species. Additionally, twenty transcripts could be
      identified that code for proteins previously detected by mass spectrometry
      analysis of protein fractions of the whipworm somatic extract that present
      immunomodulatory activities. Five of these transcripts were amongst the most
      highly expressed protein-encoding sequences in the T. trichiura adult worm.
      Besides, orthologs of proteins demonstrated to have potent immunomodulatory
      properties in related parasitic helminths were also predicted from the T.
      trichiura de novo assembled transcriptome. 

PMID- 27038557
TI  - West Nile virus in Tunisia, 2014: First isolation from mosquitoes.
AB  - Several outbreaks of human West Nile virus (WNV) infections were reported in
      Tunisia during the last two decades. Serological studies on humans as well as on
      equine showed intensive circulation of WNV in Tunisia. However, no virus
      screening of mosquitoes for WNV has been performed in Tunisia. In the present
      study, we collected mosquito samples from Central Tunisia to be examined for the
      presence of flaviviruses. A total of 102 Culex pipiens mosquitoes were collected
      in September 2014 from Central Tunisia. Mosquitoes were pooled according to the
      collection site, date and sex with a maximum of 5 specimens per pool and tested
      for the presence of flaviviruses by conventional reverse transcription heminested
      PCR and by a specific West Nile virus real time reverse transcription PCR. Of a
      total of 21 pools tested, 7 were positive for WNV and no other flavivirus could
      be evidenced in mosquito pools. In addition, WNV was isolated on Vero cells.
      Phylogenetic analysis showed that recent Tunisian WNV strains belong to lineage 1
      WNV and are closely related to the Tunisian strain 1997 (PAH 001). This is the
      first detection and isolation of WNV from mosquitoes in Tunisia. Some areas of
      Tunisia are at high risk for human WNV infections. WNV is likely to cause future
      sporadic and foreseeable outbreaks. Therefore, it is of major epidemiological
      importance to set up an entomological surveillance as an early alert system.
      Timely detection of WNV should prompt vector control to prevent future outbreaks.
      In addition, education of people to protect themselves from mosquito bites is of
      major epidemiological importance as preventive measure against WNV infection. 

PMID- 27038558
TI  - New medications for heart failure.
AB  - Heart failure is common and results in substantial morbidity and mortality.
      Current guideline-based therapies for heart failure with reduced ejection
      fraction, including beta blockers, angiotensin converting enzyme (ACE)
      inhibitors, and aldosterone antagonists aim to interrupt deleterious
      neurohormonal pathways and have shown significant success in reducing morbidity
      and mortality associated with heart failure. Continued efforts to further improve
      outcomes in patients with heart failure with reduced ejection fraction have led
      to the first new-in-class medications approved for heart failure since 2005,
      ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the
      sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan
      combines a neprilysin inhibitor that increases levels of beneficial vasodilatory
      peptides with an angiotensin receptor antagonist. On a background of previously
      approved, guideline-directed medical therapies for heart failure, these
      medications have shown improved clinical outcomes ranging from decreased
      hospitalizations in a select group of patients to a reduction in all-cause
      mortality across all pre-specified subgroups. In this review, we will discuss the
      previously established guideline-directed medical therapies for heart failure
      with reduced ejection fraction, the translational research that led to the
      development of these new therapies, and the results from the major clinical
      trials of ivabradine and sacubitril/valsartan.

PMID- 27038559
TI  - Women's experience of childbirth - A five year follow-up of the randomised
      controlled trial "Ready for Child Trial".
AB  - BACKGROUND: Few studies have assessed the long term perspective of women's
      childbirth experience as well as studying women's individual birth experience
      over time. AIM: To compare the long term perspective of the birth experience in
      nulliparous women attending a structured antenatal programme to that of women
      allocated to standard care. Moreover, to study changes in the woman's perception
      of birth and explore the birth characteristics in women reporting a less positive
      birth experience after five years compared to their reported experience shortly
      after birth. METHODS: A five-year follow-up study of a randomised controlled
      trial; "The Ready for Child" trial. Information used in the current study was
      collected from 905 nulliparous womens' questionnaires. RESULTS: More women
      reported less positive birth experiences in the long term compared to shortly
      after birth. Women receiving the structured antenatal programme reported a more
      positive birth experience in the long term compared to women in the original
      reference group. Birth characteristics of women reporting a less positive birth
      experience in the long term, irrespective of group allocation, were significantly
      more likely to experience an epidural, cardiotocography monitoring, and less
      likely to used water as pain relief and have a spontaneous vaginal birth.
      CONCLUSION AND IMPLICATIONS: Women's overall birth experience is important as it
      has a long term influence on the future health of the woman and her family.
      Reporting a good birth experience in the long term is more likely when attending
      a structured antenatal programme and if medical intervention is avoided during
      birth.

PMID- 27038560
TI  - 'Expecting and Connecting' Group Pregnancy Care: Evaluation of a collaborative
      clinic.
AB  - PROBLEM: Establishment of a service to increase clinical placement opportunities
      for midwifery students in a regional area of Queensland, Australia with unknown
      impact on all service stakeholders. BACKGROUND: Group antenatal care (known as
      Expecting and Connecting) was provided at the university campus, instigated
      collaboratively between the health service and university in response to
      population growth and student needs in a health service jurisdiction not
      otherwise serviced for public pregnancy care. QUESTION, HYPOTHESIS OR AIM: This
      study evaluated the 'Expecting and Connecting' Group Pregnancy Care service from
      the perspective of attending women, midwifery students and midwives. METHODS:
      Qualitative findings were obtained from mothers, midwives and midwifery students.
      The study was guided by Donabedian's conceptual framework to assess quality
      within a health service. Thematic analysis was used to identify themes and
      concepts from the data within the areas of structure, process and outcome.
      FINDINGS: Expecting and Connecting provided benefits to participants including an
      environment for students and pregnant women to build relationships to meet
      Continuity of Care requirements for students. Mothers reported high levels of
      satisfaction with antenatal care including the ability to develop peer support.
      DISCUSSION: The collaborative facilitation of group antenatal care by university
      and health service midwives provided a catalyst to the development of peer
      support networks within the local community and enhance opportunity for midwifery
      student requirements. CONCLUSION: The 'Expecting and Connecting' group antenatal
      care service was highly regarded by participant mothers, midwives and midwifery
      students and provided an additional source of midwifery student placement.

PMID- 27038561
TI  - Numerosity underestimation in sets with illusory contours.
AB  - People underestimate the numerosity of collections in which a few dots are
      connected in pairs by task-irrelevant lines. Such configural processing suggests
      that visual numerosity depends on the perceived scene segments, rather than on
      the perceived total area occupied by a collection. However, a methodology that
      uses irrelevant line connections may also introduce unnecessary distraction and
      variety, or obscure the perception of task-relevant items, given the saliency of
      the lines. To avoid such potentially confounding variables, we conducted four
      experiments where the line-connected dots were replaced with collinear inducers
      of Kanizsa-type illusory contours. Our participants had to compare two
      simultaneously presented collections and choose the more numerous one. Displays
      comprised c-shaped inducers and disks (Experiment 1), c-shaped inducers only
      (Experiments 2 and 4), or closed inducers (Experiment 3). One display always
      showed a 12- (Experiments 1-3) or 48-item reference pattern (Experiment 4); the
      other was a test pattern with numerosity varying between 9 and 15 (Experiments 1
      3) or 36-60 items (Experiment 4). By manipulating the number of illusory contours
      in the test patterns, the level of connectedness increased or decreased
      respectively. The fitted psychometric functions revealed an underestimation that
      increased with the number of illusory contours in Experiments 1 and 2, but was
      absent in Experiments 3 and 4, where illusory contours were more difficult to
      perceive or larger numerosities were used. Results corroborate claims that visual
      numerosity estimation depends on segmented inputs, but only within moderate
      numerical ranges.

PMID- 27038562
TI  - Misbinding of color and motion in human early visual cortex: Evidence from event
      related potentials.
AB  - One of the central tasks for the visual system is to integrate visual features
      into objects, which is referred to as the binding problem. To study the binding
      mechanisms, it has been suggested to use phenomena of feature misbinding to
      separate active feature binding from feature co-occurence. Taking advantage of a
      steady-state misbinding of color and motion, we performed psychophysical and
      event-related potential (ERP) adaptation experiments to investigate the neural
      mechanisms of the misbinding (i.e., the active color-motion binding). Human
      subjects adapted to the misbinding of color and motion, as well as their correct
      binding that was used for identifying neural processes associated with the co
      occurrence of color and motion. We found that adaptation to the misbinding and
      the correct binding could generate color-contingent motion aftereffects (CCMAEs),
      but in opposite directions. ERP adaptation effects manifested in the earliest ERP
      component C1. The C1 latency in the misbinding condition was 11ms longer than
      that in the correct binding condition. In the correct binding condition, the C1
      adaptation effect (i.e., the C1 amplitude reduction after adaptation) took place
      in the peak phase of the C1. The dipole source of the adaptation effect was
      located in V1. In the misbinding condition, the C1 adaptation effect occurred in
      the descending phase of the C1 and its dipole source was in V2. In both
      conditions, the C1 adaptation effects correlated with the CCMAEs across
      individual subjects. These findings provide human electrophysiological evidence
      that active feature binding takes place in early visual cortex, but at later
      processing stages than feature co-occurrence.

PMID- 27038563
TI  - Shoulder arthroplasty for chondrolysis.
AB  - BACKGROUND: Chondrolysis is a rare complication after shoulder arthroscopy
      leading to early joint destruction. Shoulder arthroplasty may be considered for
      end-stage chondrolysis, but concerns exist about implant survivorship, given the
      younger age of this population. This study aimed to assess pain relief, function,
      and survivorship of shoulder arthroplasty for chondrolysis and to assess risk
      factors for failure. METHODS: Between January 2000 and January 2013, 26
      consecutive shoulders with chondrolysis were treated at our institution with
      shoulder arthroplasty. All shoulders had a prior arthroscopic procedure that
      predated a phase of rapid joint destruction. Twenty-three shoulders were followed
      up for a minimum of 2 years or until reoperation (mean, 4.0 years; range, 0.7-8.6
      years). The mean age of the patients was 40 years (range, 21-58 years). Outcome
      measures included pain, range of motion, postoperative modified Neer ratings,
      American Shoulder and Elbow Surgeons scores, complications, and reoperations.
      RESULTS: At most recent follow-up, only 14 of 23 shoulders had no or mild pain.
      Overall pain scores improved from 4.7 to 2.6 points. Abduction and external
      rotation improved significantly. Five shoulders required reoperation, 2 for
      glenoid loosening and 1 each for infection, instability, and stiffness.
      Subjectively, 8 patients rated their shoulder as much better, 7 as better, 4 the
      same, and 4 worse. Most recent American Shoulder and Elbow Surgeons scores
      averaged 64 points (range, 20-95 points). CONCLUSIONS: Shoulder arthroplasty for
      the treatment of chondrolysis improves pain and range of motion. However, patient
      satisfaction is variable. Early follow-up shows a higher than expected rate of
      reoperation (25%). Patients undergoing shoulder arthroplasty for chondrolysis
      should be counseled appropriately about expectations after surgery.

PMID- 27038564
TI  - Comparison of shoulder internal rotation passive range of motion in various
      positions in nonathletic persons and the establishment of normative values for
      the sidelying position.
AB  - BACKGROUND: Loss of shoulder internal rotation (IR) range of motion (ROM) is
      prevalent in overhead athletes, but it can also be seen in nonathletic persons. A
      paucity of normative data exists, however, for shoulder IR ROM in positions other
      than supine, especially in nonathletic persons. The aim of this study was to
      determine shoulder IR ROM differences between the sidelying, semi-sidelying, and
      supine positions as well as to establish initial normative values for IR ROM for
      the sidelying and semi-sidelying positions in nonathletic persons. METHODS: IR
      ROM was measured on 204 nonathletic persons using the sidelying, semi-sidelying,
      and supine positions. Mean values of IR ROM for each position were calculated.
      Differences in IR ROM across the 3 positions and side-to-side differences were
      examined, including the influence of sex and age on IR ROM. RESULTS: Intra-rater
      and inter-rater reliability for the sidelying position was excellent. The
      sidelying position had significantly less IR ROM compared with the other
      positions, and there was a significant side-to-side IR ROM difference, greatest
      for the sidelying position (6.8 degrees ). Women had significantly more IR ROM
      than men did, with sidelying normative values of 49 degrees  and 55 degrees  for
      female dominant and nondominant shoulders, respectively, and 42 degrees  and 51
      degrees  for male dominant and nondominant shoulders, respectively. CONCLUSION:
      This investigation establishes initial normative IR ROM values for the sidelying
      position for both shoulders and sexes. Health care providers can begin to examine
      IR ROM deficits using these normative values for the sidelying position.

PMID- 27038565
TI  - The challenge of Propionibacterium acnes and revision shoulder arthroplasty: a
      review of current diagnostic options.
AB  - BACKGROUND: Propionibacterium acnes is the most common cause of infection after
      shoulder arthroplasty. Whereas there are several methods that can aid in the
      diagnosis of P. acnes infection, there is not a single "gold standard" because of
      the difficulties inherent in identifying this bacterium. We present an evidence
      based discussion of the demographic, clinical, and radiographic predictors of P.
      acnes infection and review the current options for diagnosis. METHODS: This
      review was written after a comprehensive analysis of the current literature
      related to shoulder periprosthetic joint infection and P. acnes identification.
      RESULTS AND CONCLUSIONS: Of the techniques reviewed, alpha-defensin had the
      highest sensitivity in detecting P. acnes infection (63%). C-reactive protein
      level and erythrocyte sedimentation rate were often normal in cases of infection.
      Whereas P. acnes can be challenging to successfully diagnose, there are several
      options that are considered preferable because of their higher sensitivities and
      specificities. The current gold standard is intraoperative culture, but major
      advances in molecular techniques may provide future improvements in diagnostic
      accuracy.

PMID- 27038566
TI  - Younger patients report similar activity levels to older patients after reverse
      total shoulder arthroplasty.
AB  - BACKGROUND: Younger patients who have undergone reverse total shoulder
      arthroplasty (RTSA) are believed to have higher activity levels that place higher
      stresses across the prosthesis, increasing the risk of failure, but there is
      little information to support or refute this supposition. The purposes of this
      study were to define the patient-reported activity levels of patients younger
      than 65 years and older than 65 years who underwent RTSA and to evaluate any
      differences between the groups. METHODS: Forty-six patients who underwent primary
      RTSA answered a questionnaire regarding their activity levels. Data were
      categorized and tabulated according to pain, range of motion, strength, and
      activity level (low, medium, and high demand). Statistical analyses were
      performed using the Fisher exact test, chi(2) test, and independent t test.
      Differences with P < .05 were considered statistically significant. RESULTS:
      Seventeen patients younger than 65 years (mean age, 57.7 years) and 29 patients
      older than 65 years (mean age, 75.2 years) were included. No significant
      differences were found for range of motion, strength, or number of activities;
      47% of younger patients and 44% of older patients reported high-demand activities
      (P = .64); 24% of younger patients and 37% of older patients reported medium
      demand use (P = .30). Patients younger than 65 years were more likely to require
      narcotic pain medication (P = .03) and to have disability (P = .0001).
      CONCLUSION: These data provide initial evidence that commonly held concerns about
      higher activity levels among younger patients placing excessive demands on the
      RTSA prosthesis may not be as important as currently thought. Rather, patients
      seem to self-regulate their activities to minimize pain and maximize essential
      functions after surgery.

PMID- 27038567
TI  - Melanocytic Lesion with a Globular Pattern Showing Changes During Short-term
      Follow-up.

PMID- 27038569
TI  - Vapor intrusion risk of lead scavengers 1,2-dibromoethane (EDB) and 1,2
      dichloroethane (DCA).
AB  - Vapor intrusion of synthetic fuel additives represented a critical yet still
      neglected problem at sites impacted by petroleum fuel releases. This study used
      an advanced numerical model to simulate the vapor intrusion risk of lead
      scavengers 1,2-dibromoethane (ethylene dibromide, EDB) and 1,2-dichloroethane
      (DCA) under different site conditions. We found that simulated EDB and DCA indoor
      air concentrations can exceed USEPA screening level (4.7 * 10(-3) MUg/m(3) for
      EDB and 1.1 * 10(-1) MUg/m(3) for DCA) if the source concentration is high enough
      (is still within the concentration range found at leaking UST site). To evaluate
      the chance that vapor intrusion of EDB might exceed the USEPA screening levels
      for indoor air, the simulation results were compared to the distribution of EDB
      at leaking UST sites in the US. If there is no degradation of EDB or only abiotic
      degradation of EDB, from 15% to 37% of leaking UST sites might exceed the USEPA
      screening level. This study supports the statements made by USEPA in the
      Petroleum Vapor Intrusion (PVI) Guidance that the screening criteria for
      petroleum hydrocarbon may not provide sufficient protectiveness for fuel releases
      containing EDB and DCA. Based on a thorough literature review, we also compiled
      previous published data on the EDB and DCA groundwater source concentrations and
      their degradation rates. These data are valuable in evaluating EDB and DCA vapor
      intrusion risk. In addition, a set of refined attenuation factors based on site
      specific information (e.g., soil types, source depths, and degradation rates)
      were provided for establishing site-specific screening criteria for EDB and DCA.
      Overall, this study points out that lead scavengers EDB and DCA may cause vapor
      intrusion problems. As more field data of EDB and DCA become available, we
      recommend that USEPA consider including these data in the existing PVI database
      and possibly revising the PVI Guidance as necessary. 

PMID- 27038568
TI  - Comparative effect of physicomechanical and biomolecular cues on zone-specific
      chondrogenic differentiation of mesenchymal stem cells.
AB  - Current tissue engineering approaches to regeneration of articular cartilage
      rarely restore the tissue to its normal state because the generated tissue lacks
      the intricate zonal organization of the native cartilage. Zonal regeneration of
      articular cartilage is hampered by the lack of knowledge for the relation between
      physical, mechanical, and biomolecular cues and zone-specific chondrogenic
      differentiation of progenitor cells. This work investigated in 3D the effect of
      TGF-beta1, zone-specific growth factors, optimum matrix stiffness, and adding
      nanofibers on the expression of chondrogenic markers specific to the superficial,
      middle, and calcified zones of articular cartilage by the differentiating human
      mesenchymal stem cells (hMSCs). Growth factors included BMP-7, IGF-1, and
      hydroxyapatite (HA) for the superficial, middle, and calcified zones,
      respectively; optimum matrix stiffness was 80 kPa, 2.1 MPa, and 320 MPa; and
      nanofibers were aligned horizontal, random, and perpendicular to the gel surface.
      hMSCs with zone-specific cell densities were encapsulated in engineered hydrogels
      and cultured with or without TGF-beta1, zone-specific growth factor, optimum
      matrix modulus, and fiber addition and cultured in basic chondrogenic medium. The
      expression of encapsulated cells was measured by mRNA, protein, and biochemical
      analysis. Results indicated that zone-specific matrix stiffness had a dominating
      effect on chondrogenic differentiation of hMSCs to the superficial and calcified
      zone phenotypes. Addition of aligned nanofibers parallel to the direction of gel
      surface significantly enhanced expression of Col II in the superficial zone
      chondrogenic differentiation of hMSCs. Conversely, biomolecular factor IGF-1 in
      combination with TGF-beta1 had a dominating effect on the middle zone
      chondrogenic differentiation of hMSCs. Results of this work could potentially
      lead to the development of multilayer grafts mimicking the zonal organization of
      articular cartilage.

PMID- 27038570
TI  - Occurrence and distribution of antibiotics, antibiotic resistance genes in the
      urban rivers in Beijing, China.
AB  - The occurrence and distribution of sulfonamide and tetracycline, corresponding
      bacterial resistant rate and resistance genes (ARGs) and two integrase genes were
      investigated in seven urban rivers in Beijing, China. The total concentration of
      sulfonamide and tetracycline ranged from 1.3 * 10(1)-1.5 * 10(3) ng/L and 3.9 *
      10(1)-5.4 * 10(4) ng/L for water, and 1.0 * 10(0)-2.7 * 10(2) and 3.1 * 10(1)-1.6
      * 10(2) ng/g for sediment, respectively. The sul resistant rate was 2-3 times
      higher than tet resistant rate in both surface water and sediment. The average
      rate of sul resistance and tet resistance were up to 81.3% and 38.6% in surface
      water, 89.1% and 69.4% in the sediment, respectively. The sul1, tetA and tetE
      genes were predominant in term of the absolute abundance. The absolute abundance
      of ARGs in Wenyu River and Qinghe River, which were close to the direct
      discharging sites, were 5-50 times higher than those in the other investigated
      urban rivers, suggesting that the source release played an important role in the
      distribution of ARGs. The sul1 and sul2 genes had positive correlation (p < 0.05)
      with sulfonamides, and the tet resistance genes was significantly correlated with
      tetracyclines (p < 0.05), indicating that some ARGs and antibiotics in the urban
      rivers had identical sources of pollution. Considering principal component
      analysis, sampling sites (QH5, QH6, B1, B2, B3 and BX2) intimated that a complex
      interplay of processes govern fate and transport of ARGs in the junction of
      rivers. These results are significant to understand the fate, and the
      contribution of ARGs from the source release. In view of the large-scale
      investigation of urban rivers system in Beijing, it reflected the bacterial
      resistance in sewage drainage system. Such investigation highlights the
      management on controlling the pollutant release which was seemed as a major
      driving force for the maintenance and propagation of many ARGs during the
      development of urbanization in the future. 

PMID- 27038571
TI  - Evaluation of the use of moss transplants (Pseudoscleropodium purum) for
      biomonitoring different forms of air pollutant nitrogen compounds.
AB  - We investigated whether three different types of moss transplants (devitalized
      moss bags with and without cover and auto-irrigated moss transplants) are
      suitable for use as biomonitors of the deposition of oxidised and/or reduced
      forms of N. For this purpose, we determined whether the concentration of
      atmospheric NO2 was related to the % N, delta(15)N and the activity of the enzyme
      biomarkers phosphomonoesterase (PME) and nitrate reductase (NR) in the tissues of
      moss transplants. We exposed the transplants in 5 different environments of
      Galicia (NW Spain) and Cataluna (NE Spain): industrial environments, urban and
      periurban environments, the surroundings of a cattle farm and in a monitoring
      site included in the sampling network of the European Monitoring Programme. The
      results showed that the moss in the auto-irrigated transplants was able of
      incorporating the N in its tissues because it was metabolically active, whereas
      in devitalized moss bags transplants, moss simply intercepts physically the N
      compounds that reached it in particulate or gaseous form. In addition, this
      devitalization could limit the capacity of moss to capture gaseous compounds
      (i.e. reduced N) and to reduce the oxidised compounds that reach the specimens.
      These findings indicate that devitalized moss transplants cannot be used to
      monitor either oxidised or reduced N compounds, whereas transplants of
      metabolically active moss can be used for this purpose. Finally, the NR and PME
      biomarkers should be used with caution because of the high variability in their
      activities and the limits of quantification should be evaluated in each case. 

PMID- 27038572
TI  - Potential health benefits of controlling dust emissions in Beijing.
AB  - Although the adverse impact of fine particulate matter (i.e., PM2.5) on human
      health has been well acknowledged, little is known of the health effects of its
      specific constituents. Over the past decade, the annual average dust
      concentrations in Beijing were approximately ~14 MUg m(-3), a value that poses a
      great threat to the city's 20 million residents. In this study, we quantify the
      potential long-term health damages in Beijing resulting from the dust exposure
      that occurred from 2000 to 2011. Each year in Beijing, nearly 4000 (95% CI: 1000
      7000) premature deaths may be associated with long-term dust exposure, and ~20%
      of these deaths are attributed to lung cancer. A decomposition analysis of the
      inter-annual variability of premature deaths in Beijing indicates that dust
      concentrations determine the year-to-year tendency, whereas population growth and
      lung cancer mortality rates drive the increasing tendency of premature death. We
      suggest that if Beijing takes effective measures towards reducing dust
      concentrations (e.g., controlling the resuspension of road dust and the fugitive
      dust from construction sites) to a level comparable to that of New York City's,
      the associated premature deaths will be significantly reduced. This
      recommendation offers "low-hanging fruit" suggestions for pollution control that
      would greatly benefit the public health in Beijing. 

PMID- 27038573
TI  - Polychlorinated biphenyls (PCBs) in sediments/soils of different wetlands along
      100-year coastal reclamation chronosequence in the Pearl River Estuary, China.
AB  - PCBs (polychlorinated biphenyls) were determined in sediment/soil profiles to a
      depth of 30 cm from three different wetlands (i.e., ditch wetlands, riparian
      wetlands and reclaimed wetlands) of the Pearl River Estuary to elucidate their
      levels, distribution and toxic risks along a 100-year chronosequence of
      reclamation. All detected PCB congeners and the total 15 PCBs (?15 PCBs)
      decreased with depth along sediment/soil profiles in these three wetlands. The
      ?15 PCBs concentrations ranged from 17.68 to 169.26 ng/g in surface
      sediments/soils. Generally, old wetlands tended to have higher PCB concentrations
      than younger ones. The dominant PCB congeners at all sampling sites were light
      PCB homologues (i.e., tetra-CBs and tri-CBs). According to the sediment quality
      guideline, the average PCB concentrations exceeded the threshold effects level
      (TEL, 21.6 ng/g) at most of the sampling sites, exhibiting possible adverse
      biological effects, which were dominantly caused by light PCB congeners. The
      total toxic equivalent (TEQ) concentrations of 10 dioxin-like PCBs (DL-PCBs)
      detected at all sampling sites ranged from 0.04 to 852.7 (10(-3) ng/g), mainly
      affected by PCB126. Only DL-PCB concentrations in ditch and riparian wetland
      sediments with 40-year reclamation histories (i.e., D40 and Ri40) exhibited
      moderate adverse biological effects according to SQGQ values. Principal component
      analysis indicated that PCBs in three wetland sediments/soils mainly originated
      from Aroclor 1016, 1242, and 1248. Correlation analysis showed that sediment/soil
      organic carbon content had a significant correlation with the concentrations of
      several PCB congeners (P < 0.05), whereas no significant correlations were
      observed between any PCBs congeners and grain size or aggregate content (P >
      0.05). 

PMID- 27038574
TI  - An emphasis of hydrogen sulfide-cysteine cycle on enhancing the tolerance to
      chromium stress in Arabidopsis.
AB  - Increasing attention has been focused on the health of vegetables and grains
      grown in the contaminated agricultural soil, it is thus meaningful to find ways
      to reduce the heavy metals (HMs) accumulation in plants. As sulfur is considered
      to be an essential macronutrient for plant stress defenses, the important role of
      sulfur assimilation in plants responding to HMs stress has been followed.
      However, the potential mechanism of the only sulfur-containing gasotransmitter
      hydrogen sulfide (H2S) and its main endogenously generated substrate, cysteine
      (Cys), in plant defense is poorly understood. The physiological and biochemical
      methods together with qRT-PCR were used to explore the response pattern of H2S
      Cys cycle in plants resisting to chromium (Cr(6+)) stress. Our results suggested
      that Cr(6+) stress inhibited Arabidopsis root elongation, increased the H2S and
      Cys contents time-dependently, and H2S production was activated earlier than Cys.
      Furthermore, H2S increased Cys accumulation more quickly than Cr(6+) stress. The
      qRT-PCR results revealed that H2S up-regulated the Cys generation-related genes
      OASTLa, SAT1 and SAT5 expression levels, and that SAT1 and SAT5 expression was
      elevated for a longer duration. Data suggested that H2S might regulate Cys
      metabolism-related genes expression to participate in Cr(6+)-mediated Cys
      accumulation. H2S and Cys relieved the root elongation inhibition caused by
      Cr(6+) in Arabidopsis. Both H2S and Cys enhanced glutathione generation and
      activated phytochelatins (PCs) synthesis by up-regulating PCS1 and PCS2
      expression levels to fight against Cr(6+) stress. Besides regulating the
      expression of PCs synthase encoding genes, H2S might promote metallothioneins
      accumulation by significantly increasing the MT2A gene expression. Overall, H2S
      and H2S-induced Cys accumulation (H2S-Cys system) was critical in imparting
      Cr(6+) tolerance in Arabidopsis. This paper is the first to indicate that
      gasotransmitter H2S induced Cys accumulation in Arabidopsis Cr(6+)-stress defense
      and provides evidence for more extensive studies of the H2S signaling pathway. 

PMID- 27038575
TI  - Thallium dispersal and contamination in surface sediments from South China and
      its source identification.
AB  - Thallium (Tl) is a non-essential element in humans and it is considered to be
      highly toxic. In this study, the contents, sources, and dispersal of Tl were
      investigated in surface sediments from a riverine system (the western Pearl River
      Basin, China), whose catchment has been contaminated by mining and roasting of Tl
      bearing pyrite ores. The isotopic composition of Pb and total contents of Tl and
      other relevant metals (Pb, Zn, Cd, Co, and Ni) were measured in the pyrite ores,
      mining and roasting wastes, and the river sediments. Widespread contamination of
      Tl was observed in the sediments across the river, with the highest concentration
      of Tl (17.3 mg/kg) measured 4 km downstream from the pyrite industrial site.
      Application of a modified Institute for Reference Materials and Measurement
      (IRMM) sequential extraction scheme in representative sediments unveiled that 60
      90% of Tl and Pb were present in the residual fraction of the sediments. The
      sediments contained generally lower (206)Pb/(207)Pb and higher (208)Pb/(206)Pb
      ratios compared with the natural Pb isotope signature (1.2008 and 2.0766 for
      (206)Pb/(207)Pb and (208)Pb/(206)Pb, respectively). These results suggested that
      a significant fraction of non-indigenous Pb could be attributed to the mining and
      roasting activities of pyrite ores, with low (206)Pb/(207)Pb (1.1539) and high
      (208)Pb/(206)Pb (2.1263). Results also showed that approximately 6-88% of Tl
      contamination in the sediments originated from the pyrite mining and roasting
      activities. This study highlights that Pb isotopic compositions could be used for
      quantitatively fingerprinting the sources of Tl contamination in sediments. 

PMID- 27038576
TI  - Selenium exposure results in reduced reproduction in an invasive ant species and
      altered competitive behavior for a native ant species.
AB  - Competitive ability and numerical dominance are important factors contributing to
      the ability of invasive ant species to establish and expand their ranges in new
      habitats. However, few studies have investigated the impact of environmental
      contamination on competitive behavior in ants as a potential factor influencing
      dynamics between invasive and native ant species. Here we investigated the
      widespread contaminant selenium to investigate its potential influence on
      invasion by the exotic Argentine ant, Linepithema humile, through effects on
      reproduction and competitive behavior. For the fecundity experiment, treatments
      were provided to Argentine ant colonies via to sugar water solutions containing
      one of three concentrations of selenium (0, 5 and 10 MUg Se mL(-1)) that fall
      within the range found in soil and plants growing in contaminated areas.
      Competition experiments included both the Argentine ant and the native Dorymyrmex
      bicolor to determine the impact of selenium exposure (0 or 15 MUg Se mL(-1)) on
      exploitation- and interference-competition between ant species. The results of
      the fecundity experiment revealed that selenium negatively impacted queen
      survival and brood production of Argentine ants. Viability of the developing
      brood was also affected in that offspring reached adulthood only in colonies that
      were not given selenium, whereas those in treated colonies died in their larval
      stages. Selenium exposure did not alter direct competitive behaviors for either
      species, but selenium exposure contributed to an increased bait discovery time
      for D. bicolor. Our results suggest that environmental toxins may not only pose
      problems for native ant species, but may also serve as a potential obstacle for
      establishment among exotic species. 

PMID- 27038577
TI  - Effect of bacteria on the transport and deposition of multi-walled carbon
      nanotubes in saturated porous media.
AB  - The influence of bacteria on the transport and deposition behaviors of carbon
      nanotubes (CNTs) in quartz sand was examined in both NaCl (5 and 25 mM ionic
      strength) and CaCl2 (0.3 and 1.2 mM ionic strength) solutions at unadjusted pH
      (5.6-5.8) by direct comparison of both breakthrough curves and retained profiles
      in both the presence and absence of bacteria. Two types of widely utilized CNTs,
      i.e., carboxyl- and hydroxyl-functionalized multi-walled carbon nanotubes (MWCNT
      COOH and MWCNT-OH, respectively), were employed as model CNTs and Escherichia
      coli was utilized as the model bacterium. The results showed that, for both types
      of MWCNTs under all examined conditions, the breakthrough curves were higher in
      the presence of bacteria, while the retained profiles were lower, indicating that
      the co-presence of bacteria in suspension increased the transport and decreased
      the deposition of MWCNTs in porous media, regardless of ionic strength or ion
      valence. Complementary characterizations and extra column tests demonstrated that
      competition by bacteria for deposition sites on the quartz sand surfaces was a
      major (and possibly the sole) contributor to the enhanced MWCNTs transport in
      porous media. 

PMID- 27038578
TI  - Relative contribution of iron reduction to sediments organic matter
      mineralization in contrasting habitats of a shallow eutrophic freshwater lake.
AB  - Iron reduction is one of the important organic matter (OM) mineralization pathway
      in sediments. Here we investigated the rates and the relative contribution of
      iron reduction to OM mineralization in Zhushan bay (ZSB, cyanobacterial bloom
      biomass (CBB)-dominated habitats) and East Taihu Lake (ETL, submerged macrophypes
      (SM)-dominated habitats) of Lake Taihu, China. Anaerobic microcosm incubation
      revealed that the rate of iron reduction at ZSB (4.42 MUmol cm(-3) d(-1)) in
      summer was almost 1.5 times higher than at ETL (3.13 MUmol cm(-3) d(-1)). Iron
      reduction accounted for 66.5% (ZSB) and 31.8% (ETL) of total anaerobic carbon
      mineralization, respectively. No detectable methanogenesis was found at ZSB,
      while methanogenesis was responsible for 16.7% of total anaerobic respiration in
      sediments of ETL. Geochemical analysis of solid phase constituents indicated that
      ZSB surface sediments experienced highly oxidizing conditions with much higher
      amorphous Fe(III) (71 mmol m(-2)) than ETL (11 mmol m(-2)). Conversely, AVS
      inventories at ETL (38 mmol m(-2)) were up to 30 times higher than at ZSB (1.27
      mmol m(-2)), indicating significant sulfate reduction in sediments of ETL.
      Overall results suggested that varying carbon sources and distinct geochemical
      characterizations of the sediments in contrasting habitats significantly
      influenced the rate of iron reduction and the pathway of C mineralization in a
      large freshwater lake. 

PMID- 27038579
TI  - Processed aconite root and its active ingredient neoline may alleviate
      oxaliplatin-induced peripheral neuropathic pain.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Processed aconite root (PA, the root of Aconitum
      carmichaeli, Ranunculaceae) is a crude drug used in traditional Chinese or
      Japanese kampo medicine to generate heat in the body and to treat pain associated
      with coldness. Oxaliplatin (L-OHP) is a platinum-based anticancer drug that
      frequently causes acute and chronic peripheral neuropathies, including cold and
      mechanical hyperalgesia. AIM OF THE STUDY: We investigated the effects of PA on L
      OHP-induced peripheral neuropathies and identified the active ingredient within
      PA extract. MATERIALS AND METHODS: L-OHP was intraperitoneally injected into
      mice, and PA boiled water extract was orally administered. Cold and mechanical
      hyperalgesia were evaluated using the acetone test and the von Frey filament
      method, respectively. Dorsal root ganglion (DRG) neurons were isolated from
      normal mice and cultured with L-OHP with or without PA extract. Cell viability
      and neurite elongation were evaluated. RESULTS: PA extract significantly
      attenuated cold and mechanical hyperalgesia induced by L-OHP in mice. In cultured
      DRG neurons, L-OHP reduced cell viability and neurite elongation in a dose
      dependent manner. Treatment with PA extract significantly alleviated the L-OHP
      induced reduction of neurite elongation, while the cytotoxicity of L-OHP was not
      affected. Using activity-guided fractionation, we isolated neoline from PA
      extract as the active ingredient. Neoline significantly alleviated L-OHP-induced
      reduction of neurite elongation in cultured DRG neurons in a concentration
      dependent manner. Moreover, subcutaneous injection of neoline attenuated cold and
      mechanical hyperalgesia in L-OHP-treated mice. PA extract and neoline did not
      show sedation and motor impairment. CONCLUSIONS: The present study indicates that
      PA and its active ingredient neoline are promising agents to alleviate L-OHP
      induced neuropathic pain.

PMID- 27038580
TI  - Photocatalytic activity of the modified composite photocatalyst by introducing
      the rich-nitrogen complex to the Bi2WO6.
AB  - A metal-organic complex [Cd2(L)(N3)4].DMF was prepared by the reaction of
      Cd(NO3)2.4H2O, NaN3 and ligand L (L: 1,4-bis(bis(3,5-dimethyl-1H-pyrazol-1
      yl)methyl)benzene) in a DMF system. And the complex was characterized by
      elemental analysis, IR spectroscopy, UV-vis spectroscopy, thermal gravimetric
      technology, X-ray powder diffraction and single-crystal X-ray diffraction.
      Furthermore, the complex was combined with Bi2WO6 to form a composite, which was
      used as photocatalyst to degrade the basic dye methylene blue (MB) under the Xe
      lamp irradiation. The result revealed that the photocatalytic activity of the
      composite was better than that of the pure Bi2WO6 and the complex. In addition,
      the mechanism of the photocatalysis was also studied. 

PMID- 27038581
TI  - Novel pure component contribution, mean centering of ratio spectra and factor
      based algorithms for simultaneous resolution and quantification of overlapped
      spectral signals: An application to recently co-formulated tablets of
      chlorzoxazone, aceclofenac and paracetamol.
AB  - In this work, resolution and quantitation of spectral signals are achieved by
      several univariate and multivariate techniques. The novel pure component
      contribution algorithm (PCCA) along with mean centering of ratio spectra (MCR)
      and the factor based partial least squares (PLS) algorithms were developed for
      simultaneous determination of chlorzoxazone (CXZ), aceclofenac (ACF) and
      paracetamol (PAR) in their pure form and recently co-formulated tablets. The PCCA
      method allows the determination of each drug at its lambdamax. While, the mean
      centered values at 230, 302 and 253nm, were used for quantification of CXZ, ACF
      and PAR, respectively, by MCR method. Partial least-squares (PLS) algorithm was
      applied as a multivariate calibration method. The three methods were successfully
      applied for determination of CXZ, ACF and PAR in pure form and tablets. Good
      linear relationships were obtained in the ranges of 2-50, 2-40 and 2-30MUgmL(-1)
      for CXZ, ACF and PAR, in order, by both PCCA and MCR, while the PLS model was
      built for the three compounds each in the range of 2-10MUgmL(-1). The results
      obtained from the proposed methods were statistically compared with a reported
      one. PCCA and MCR methods were validated according to ICH guidelines, while PLS
      method was validated by both cross validation and an independent data set. They
      are found suitable for the determination of the studied drugs in bulk powder and
      tablets. 

PMID- 27038582
TI  - Experimental and quantum mechanical studies on the ion-pair of levocetirizine and
      bromocresol green in aqueous solutions.
AB  - In the present work, levocetirizine dihydrochloride (LEV) was found to interact
      with bromocresol green (BCG) via ion-pair formation. UV-vis and FTIR spectroscopy
      were used to validate the data obtained from quantum mechanical calculations
      (QMC). The electrostatic potential maps show that the reaction is preferred
      through the interaction of the sulfonic acid group of BCG and the quaternary
      ammonium group of LEV. The optimized geometry of the product shows that there are
      six different intermolecular hydrogen bonds between the studied molecules
      resulting from the ionic attraction between the oppositely charged groups. The UV
      vis spectra suggest the formation of an ion-pair. This finding is contradicting
      with the previous charge-transfer hypothesis. 

PMID- 27038583
TI  - Mechanism, kinetics, and pathways of self-sensitized sunlight photodegradation of
      phenylarsonic compounds.
AB  - Being highly water-soluble, phenylarsonic feed additives discharged in animal
      wastes can easily accumulate in surface water bodies. The photodegradation
      mechanism, kinetics, and pathways of p-arsanilic acid (p-ASA), 4
      hydrophenylarsonic acid (4-HPAA), and phenylarsonic acid (PAA) in water under
      simulated and natural sunlight irradiation were investigated. The -AsO(OH)2 group
      was cleaved from the aromatic ring during photodegradation, and p-benzoquinone
      and p-hydroquinone were formed as the major organic degradation intermediates.
      Experimental results did not indicate any significant direct photolysis of the
      phenylarsonic compounds under simulated and natural sunlight irradiation, but
      consistently showed that they sensitized the formation of singlet oxygen, which
      was responsible for their photodegradation and oxidation of the As(III) released.
      A simple (1)O2-based "heterogeneous" model was developed, which could well
      describe the kinetics of (1)O2 formation and phenylarsonic compound
      photodegradation under various conditions. Indirect photolysis caused by
      inorganic ions commonly present in natural waters was negligible, while natural
      organic matter could significantly inhibit their photodegradation. The half-lives
      of p-ASA, 4-HPAA, and PAA photodegradation under simulated sunlight irradiation
      (765 W m(-2), 25  degrees C) were 11.82 +/- 0.19, 20.06 +/- 0.10, and 135 +/- 6.0
      min, respectively, while their degradation rates under natural sunlight in the
      Pearl River Delta of southern China were 5 times slower due to lower irradiation
      intensity and water temperatures (19-23  degrees C).

PMID- 27038584
TI  - Evaluation of exposure scenarios on intentional microbiological contamination in
      a drinking water distribution network.
AB  - Drinking water distribution networks are vulnerable to accidental or intentional
      contamination events. The objective of this study was to investigate the effects
      of seeding duration and concentration, exposure pathway (ingestion via drinking
      of water and tooth brushing and inhalation by taking a shower) and pathogen
      infectivity on exposure and infection risk in the case of an intentional
      pathogenic contamination in a drinking water distribution network. Seeding of a
      pathogen for 10 min and 120 min, and subsequent spreading through a drinking
      water distribution network were simulated. For exposure via drinking, actual data
      on drinking events and volumes were used. Ingestion of a small volume of water by
      tooth brushing twice a day by every person in the network was assumed. Inhalation
      of contaminated aerosol droplets took place when taking a shower. Infection risks
      were estimated for pathogens with low (r = 0.0001) and high (r = 0.1)
      infectivity. In the served population (48 000 persons) and within 24 h, about
      1400 persons were exposed to the pathogen by ingestion of water in the 10-min
      seeding scenario and about 3400 persons in the 120-min scenario. The numbers of
      exposed persons via tooth brushing were about the same as via drinking of water.
      Showering caused (inhalation) exposure in about 450 persons in the 10-min
      scenario and about 1500 in the 120-min scenario. Regardless of pathogen
      infectivity, if the seeding concentration is 10(6) pathogens per litre or more,
      infection risks are close to one. Exposure by taking a shower is of relevance if
      the pathogen is highly infectious via inhalation. A longer duration of the
      seeding of a pathogen increases the probability of exposure.

PMID- 27038585
TI  - Multivariate statistical analysis of water chemistry conditions in three
      wastewater stabilization ponds with algae blooms and pH fluctuations.
AB  - The wastewater stabilization ponds (WSPs) at a wastewater treatment facility in
      eastern Ontario, Canada, have experienced excessive algae growth and high pH
      levels in the summer months. A full range of parameters were sampled from the
      system and the chemical dynamics in the three WSPs were assessed through
      multivariate statistical analysis. The study presents a novel approach for
      exploratory analysis of a comprehensive water chemistry dataset, incorporating
      principal components analysis (PCA) and principal components (PC) and partial
      least squares (PLS) regressions. The analyses showed strong correlations between
      chl-a and sunlight, temperature, organic matter, and nutrients, and weak and
      negative correlations between chl-a and pH and chl-a and DO. PCA reduced the data
      from 19 to 8 variables, with a good fit to the original data matrix (similarity
      measure of 0.73). Multivariate regressions to model system pH in terms of these
      key parameters were performed on the reduced variable set and the PCs generated,
      for which strong fits (R(2) > 0.79 with all data) were observed. The
      methodologies presented in this study are applicable to a wide range of natural
      and engineered systems where a large number of water chemistry parameters are
      monitored resulting in the generation of large data sets.

PMID- 27038586
TI  - Modeling the formation of TOCl, TOBr and TOI during chlor(am)ination of drinking
      water.
AB  - The use of chlorine and chloramines in drinking water disinfection may produce
      innumerable halogenated disinfection byproducts (DBPs). Because of the
      impossibility of measuring the concentration and evaluating the toxicity of each
      individual halogenated DBP in a water sample, total organic halogen (TOX) as a
      collective parameter and a toxicity indicator for all the halogenated DBPs has
      been gaining popularity in recent years. TOX can be divided into total organic
      chlorine (TOCl), total organic bromine (TOBr), and total organic iodine (TOI).
      Previously, the authors' group studied the formation kinetics of TOCl and TOBr in
      chlor(am)ination using two models. In this study, we further explored the
      formation kinetics of TOI as well as TOCl and TOBr during chlor(am)ination by
      carefully selecting a series of iodine-related reactions and incorporating them
      into the two kinetic models. The models well predicted the levels of TOCl, TOBr,
      TOI, and total chlorine residual during chlorination and chloramination of
      simulated raw waters. According to the modeling results, 57.1-73.6% of the total
      generated iodinated DBPs in chlorination was converted to their chlorinated and
      brominated analogues by the substitution with hypochlorous acid and hypobromous
      acid; while in chloramination, with the presence of excessive monochloramine, the
      formed hypoiodous acid might react with monochloramine to form an iodine
      substituted intermediate (proposed as chloroiodamine), which was responsible for
      41.4-49.8% of the total generated iodinated DBPs, and meantime 51.9-52.6% of the
      total generated iodinated DBPs underwent deiodination via the base-catalyzed
      hydrolysis. The models were successfully applied in determining the lag time
      between the dosages of chlorine and ammonia, a challenging issue in chlorine
      chloramine sequential treatment. This study provided important insights into
      kinetic reactions that control the formation of overall halogenated DBPs in
      chlor(am)ination.

PMID- 27038587
TI  - The therapeutic use of cannabinoids: Forensic aspects.
AB  - Since 2013 in the Italian market has been introduced the Nabiximols, a drug
      containing two of the main active cannabinoids: Delta(9)-tetrahydrocannabinol
      (Delta(9)-THC) and cannabidiol (CBD). This drug has been approved in Italy in the
      treatment of Multiple Sclerosis (MS). It is an oral spray formulation and each
      puff of 100MUl contains 2.7mg of Delta(9)-THC and 2.5mg of CBD. In the present
      study we analyzed urine and blood samples collected from a group of 20 patients
      treated with Nabiximols in order to evaluate: blood Delta(9)-THC concentrations
      in relation to the dose administered and the duration of treatment and the
      potentiality of this medication to be used for drug habit. METHODS: The study was
      conducted on a sample group of patients affected by MS, of both sexes, age: 49-61
      years, treated with Nabiximols for short (28 days) or long-term. The results of
      our study allow affirming that it is unlikely to use this medication for drug
      habit or to sale it in the black market because of the low blood concentrations
      available and of its high costs. These statements were confirmed by: (a) the low
      Delta(9)-THC concentrations in the pharmaceutical formulation; (b) the low blood
      concentrations produced by Nabiximols administration, more than 10 times smaller
      than the blood concentrations known to produce psychotropic effects; (c) the
      presence of CBD (Delta(9)-THC natural antagonist); (d) the route of
      administration (inhaled, not smoked).

PMID- 27038588
TI  - Exposure to ionizing radiation and brain cancer incidence: The Life Span Study
      cohort.
AB  - BACKGROUND: Ionizing radiation is a cause of cancer. This paper examines the
      effects of radiation dose and age at exposure on the incidence of brain cancer
      using data from the Life Span Study (LSS) of atomic bomb survivors. METHODS: The
      Radiation Effects Research Foundation website provides demographic details of the
      LSS population, estimated radiation doses at time of bomb in 1945, person years
      of follow-up and incident cancers from 1958 to 1998. We modelled brain cancer
      incidence using background-stratified Poisson regression, and compared the excess
      relative risk (ERR) per Gray (Gy) of brain dose with estimates from follow-up
      studies of children exposed to diagnostic CT scans. RESULTS: After exposure to
      atomic bomb radiation at 10 years of age the estimated ERR/Gy was 0.91 (90%CI
      0.53, 1.40) compared with 0.07 (90%CI -0.27, 0.56) following exposure at age 40.
      Exposure at 10 years of age led to an estimated excess of 17 brain tumors per
      100,000 person year (pyr) Gy by 60 years of age. These LSS estimates are
      substantially less than estimates based on follow-up of children exposed to CT
      scans. CONCLUSION: Estimates of ERR/Gy for brain cancers in the LSS and
      haemangioma cohorts seem much smaller than estimates of risk for young persons in
      the early years after exposure to CT-scans. This could be due to reverse
      causation bias in the CT cohorts, diagnostic error, measurement error with
      radiation doses, loss of early follow-up in the LSS, or non-linearity of the dose
      response curve.

PMID- 27038589
TI  - [Thromboembolic events and Bardet-Biedl syndrome].

PMID- 27038590
TI  - [Recurrent fever in a patient with obstructive pulmonary disease (COPD) who works
      as a welder].

PMID- 27038592
TI  - Ethanol Toxicity During Brain Development: Alterations of Excitatory Synaptic
      Transmission in Immature Organotypic Hippocampal Slice Cultures.
AB  - BACKGROUND: The developing brain is particularly vulnerable to alcohol: Drinking
      during pregnancy can lead to a number of physical, learning, and behavioral
      disorders in the newborn. It has been demonstrated that immature and mature brain
      tissues display a differential sensitivity to ethanol (EtOH) toxicity and that
      cerebral structure and function are diversely impaired according to the stage of
      synaptic maturation. METHODS: Rat organotypic hippocampal slice cultures were
      exposed for 7 days to EtOH (100 to 300 mM) after 2 days (immature) or 10 days
      (mature) of culture in vitro; EtOH was then removed from the medium, and 24 hours
      later, slices were analyzed by fluorescence microscopy, Western blotting,
      electrophysiology, and electron microscopy to explore the molecular mechanisms of
      EtOH toxicity in the developing hippocampus. RESULTS: EtOH withdrawal elicited a
      selective CA1 pyramidal cell injury in mature slices, but not in immature slices.
      A significant increase in the expression of pre- and postsynaptic proteins in
      mature slices revealed that slice maturation is presumably associated with the
      development of new synapses. Incubation with chronic EtOH for 7 days and its
      removal from the medium induced a significant decrease in GluA1 and GluA2
      expression levels; a significant reduction in the expression of synaptophysin and
      GluN2A was observed only after EtOH withdrawal. Whole-cell patch-clamp recordings
      showed that incubation with EtOH for 7 days induced a significant decrease in
      spontaneous excitatory postsynaptic current (sEPSC) frequency in CA1 pyramidal
      cells of immature slices and a trend toward a decrease in sEPSC amplitude.
      Electron microscopy revealed a disorganization of neurotubuli in immature slices
      after chronic exposure to EtOH. CONCLUSIONS: These results indicate that
      prolonged incubation with EtOH and its subsequent withdrawal from the medium
      induce an impairment of excitatory synaptic transmission and possibly an
      incorrect formation of neuronal circuits in developing hippocampus in vitro,
      which is suggestive of mechanisms that may lead to mental retardation in fetal
      alcohol spectrum disorders.

PMID- 27038591
TI  - Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in
      Neural Stem Cells.
AB  - The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial
      increases in fetal abnormalities and microcephaly. However, information about the
      underlying molecular and cellular mechanisms connecting viral infection to these
      defects remains limited. In this study we have examined the expression of
      receptors implicated in cell entry of several enveloped viruses including ZIKV
      across diverse cell types in the developing brain. Using single-cell RNA-seq and
      immunohistochemistry, we found that the candidate viral entry receptor AXL is
      highly expressed by human radial glial cells, astrocytes, endothelial cells, and
      microglia in developing human cortex and by progenitor cells in developing
      retina. We also show that AXL expression in radial glia is conserved in
      developing mouse and ferret cortex and in human stem cell-derived cerebral
      organoids, highlighting multiple experimental systems that could be applied to
      study mechanisms of ZIKV infectivity and effects on brain development.

PMID- 27038593
TI  - Alcohol, Methamphetamine, and Marijuana Exposure Have Distinct Effects on the
      Human Placenta.
AB  - BACKGROUND: Animal studies have demonstrated adverse effects of prenatal alcohol
      exposure on placental development, but few studies have examined these effects in
      humans. Little is known about effects of prenatal exposure to methamphetamine,
      marijuana, and cigarette smoking on placental development. METHODS: Placentas
      were collected from 103 Cape Coloured (mixed ancestry) pregnant women recruited
      at their first antenatal clinic visit in Cape Town, South Africa. Sixty-six heavy
      drinkers and 37 nondrinkers were interviewed about their alcohol, cigarette
      smoking, and drug use at 3 antenatal visits. A senior pathologist, blinded to
      exposure status, performed comprehensive pathology examinations on each placenta
      using a standardized protocol. In multivariable regression models, effects of
      prenatal exposure were examined on placental size, structure, and presence of
      infections and meconium. RESULTS: Drinkers reported a binge pattern of heavy
      drinking, averaging 8.0 drinks/occasion across pregnancy on 1.4 d/wk. 79.6%
      smoked cigarettes; 22.3% used marijuana; and 17.5% used methamphetamine. Alcohol
      exposure was related to decreased placental weight and a smaller placenta-to
      birthweight ratio. By contrast, methamphetamine was associated with larger
      placental weight and a larger placenta-to-birthweight ratio. Marijuana was also
      associated with larger placental weight. Alcohol exposure was associated with
      increased risk of placental hemorrhage. Prenatal alcohol, drug, and cigarette use
      were not associated with chorioamnionitis, villitis, deciduitis, or maternal
      vascular underperfusion. Alcohol and cigarette smoking were associated with a
      decreased risk of intrauterine passing of meconium, a sign of acute fetal stress
      and/or hypoxia; methamphetamine, with an increased risk. CONCLUSIONS: This is the
      first human study to show that alcohol, methamphetamine, and marijuana were
      associated with distinct patterns of pathology, suggesting different mechanisms
      mediating their effects on placental development. Given the growing body of
      evidence linking placental abnormalities to neurodevelopmental deficits, these
      findings may be important in the long-term teratogenic effects of prenatal
      alcohol and drug exposure.

PMID- 27038594
TI  - Employment Status, Depression, Drinking, and Alcohol Use Disorder in Puerto Rico.
AB  - BACKGROUND: Our aim was to examine the association between employment status,
      depression, drinking, binge drinking, and DSM-5 alcohol use disorder in Puerto
      Rico. METHODS: Data are from a 2013 to 2014 household random sample of
      individuals 18 to 64 years of age in San Juan, Puerto Rico. RESULTS: Bivariate
      analyses showed that depression was 5 times higher among unemployed males than
      among those employed full time (21% vs. 4%) and 2 times higher among unemployed
      females compared to those employed part time or full time (18% vs. 7% and 9%).
      Employment status was not associated with weekly volume of drinking, but
      nonparticipation in the workforce was protective against drinking (odds ratio
      [OR] = 2.17; 95% confidence interval [CI]: 1.03 to 4.57; p < 0.05) and binge
      drinking (OR = 0.62; 95% CI = 0.39 to 0.97; p < 0.05). This association could be
      due to the fact that those not in the work force may not be working due to
      sickness or disability. Male gender was a factor of risk for being a current
      drinker (OR = 2; 95% CI = 1.53 to 2.6; p < 0.001) and binge drinking (OR = 1.69;
      95% CI = 1.29 to 2.2; p < 0.001). Male gender was protective against depression
      (OR = 0.32; 95% CI = 0.14 to 0.73; p < 0.01), but males employed only part time
      were almost 5 times more likely than females employed full time to be depressed
      (OR = 4.66; 95% CI = 1.25 to 17.38; p < 0.05). CONCLUSIONS: Employment status in
      Puerto Rico is associated with depression and with current drinking, but not with
      other alcohol-related outcomes. Perhaps Puerto Rico is a "wet" environment, where
      drinking is already at a relatively high level that is not affected by employment
      status. Perhaps the chronic high rate of unemployment in the island has also
      created familial (e.g., support) and personal level accommodations (e.g.,
      participation in the informal economy) that do not include increased drinking.

PMID- 27038595
TI  - Taking the First Full Drink: Epidemiological Evidence on Male-Female Differences
      in the United States.
AB  - BACKGROUND: This research extends prior epidemiological estimates for the United
      States and re-examines a previously described male excess in alcohol drinking.
      Its aim was to estimate fine-grained age-specific incidence of becoming a drinker
      among 12- to 24-year-old U.S. males and females, and to compare incidence
      estimates with prevalence proportions. METHODS: The study population is 12- to 24
      year-old noninstitutionalized U.S. civilian residents. Estimates are from 12
      successive U.S. National Surveys on Drug Use and Health (NSDUH), with nationally
      representative samples drawn each year from 2002 to 2013 and assessed via
      computer-assisted self-interviews (n ~ 390,000). Analysis-weighted incidence and
      prevalence estimates are generated using the NSDUH Restricted Data Analysis
      System for 6 year-pairs. Meta-analysis-derived summary estimates are provided,
      treating each year-pair as a replication. RESULTS: In this 21st century evidence,
      there no longer is male excess of incidence with respect to underage drinking.
      Indeed, in mid-adolescence, there is a clear female excess for the risk of
      becoming an underage drinker. Meta-analytic summaries disclosed no other male
      female differences in incidence. Nevertheless, a male excess in the prevalence of
      recently active drinking can be seen after the age of 19 years. CONCLUSIONS: This
      new evidence from the United States shows that the so-called "gender gap" in risk
      of becoming a drinker has narrowed to the point of there being no gap at all.
      Indeed, in mid-adolescence, risk of starting to drink is greater for females than
      for males.

PMID- 27038596
TI  - Alcohol Use During Pregnancy is Associated with Specific Alterations in MicroRNA
      Levels in Maternal Serum.
AB  - BACKGROUND: Given the challenges of confirming prenatal alcohol exposure (PAE)
      during pregnancy using currently established biomarkers of alcohol consumption,
      we examined whether serum microRNAs (miRNAs) may serve as stable biomarkers for
      PAE. Alterations in the levels of specific circulating miRNAs have been
      associated with various disease states and in animal models of fetal alcohol
      spectrum disorder. METHODS: Pregnant women in this prospective study were
      recruited from substance abuse and general maternity clinics affiliated with the
      University of New Mexico. Serum was collected at the time of admission for
      delivery from 14 subjects who reported >=1 binge-drinking episode or >=3
      drinks/wk during pregnancy and 16 subjects who reported abstinence during
      pregnancy and tested negative for 5 ethanol biomarkers. Total RNA was isolated
      from serum and used for microarray analysis. RESULTS: False discovery rate
      corrected analyses of covariance revealed that 55 miRNAs were significantly
      altered between the 2 groups. Hierarchical clustering using only the
      significantly altered miRNAs grouped samples into alcohol-consuming and non
      alcohol-consuming individuals. Discriminant analysis then identified miRs-122*, 
      126, -216b, -221*, -3119, -3942-5p, -4704-3p, -4743, -514-5p, and -602 as the top
      10 discriminators between the 2 groups. Ingenuity Pathway Analysis of putative
      miRNA targets illustrated that miRNAs identified in this study are involved in
      biological pathways that mediate the effects of alcohol, such as brain-derived
      neurotrophic factor, ERK1/2, and PI3K/AKT signaling. CONCLUSIONS: This is the
      first report of alterations in serum miRNA expression that are associated with
      alcohol use during human pregnancy. These results suggest that serum miRNAs could
      be useful as biomarkers of alcohol exposure.

PMID- 27038597
TI  - Drinking Patterns Across Spring, Summer, and Fall in 462 University Students.
AB  - BACKGROUND: Student heavy drinking and associated problems are common at most
      universities and fluctuate throughout the calendar year, with marked increases
      during celebrations. Most studies of student drinking are limited to the academic
      year itself, and relatively few focus specifically on special heavy drinking
      events. Even fewer studies include drinking during summer break and subsequent
      school return. METHODS: In the context of an experimental protocol, beginning in
      January 2014, alcohol-related characteristics were evaluated 8 times over 55
      weeks for 462 college freshmen, including periods that incorporated a campus
      festival, summer, and school return. Baseline predictors of drinking quantities
      over time included demography, substance use patterns, as well as environmental
      and attitudinal characteristics. Product-moment correlations evaluated
      relationships between baseline characteristics and subsequent quantities, and
      simultaneous entry regression analyses evaluated which characteristics most
      robustly predicted usual and maximum drinks over time. RESULTS: Maximum drinks
      per occasion increased 18% from the early spring (4/8/14 to 5/6/14) to the campus
      festival period (5/7/14 to 6/3/14), decreased 29% in the summer (7/8/14 to
      8/5/14), and increased 31% on school return (10/7/14 to 11/4/14). The most robust
      predictors of higher quantities in regression analyses included items from each
      of the 3 major domains with the most consistent results seen for most baseline
      alcohol-related items and descriptive drinking norms (R(2) = 0.20 to 0.31).
      CONCLUSIONS: These data demonstrate important changes in students' drinking
      during the calendar year, including expected large increases during the month of
      a 1-day festival, large decreases over the summer, and resumption of relatively
      high quantities upon return to school.

PMID- 27038598
TI  - Adolescent Choline Supplementation Attenuates Working Memory Deficits in Rats
      Exposed to Alcohol During the Third Trimester Equivalent.
AB  - BACKGROUND: Children exposed to alcohol prenatally may suffer from behavioral and
      cognitive alterations that adversely affect their quality of life. Animal studies
      have shown that perinatal supplementation with the nutrient choline can attenuate
      ethanol's adverse effects on development; however, it is not clear how late in
      development choline can be administered and still effectively reduce the
      consequences of prenatal alcohol exposure. Using a rodent model, this study
      examined whether choline supplementation is effective in mitigating alcohol's
      teratogenic effects when administered during adolescence/young adulthood.
      METHODS: Sprague-Dawley rats were exposed to alcohol (5.25 g/kg/d) during the
      third trimester equivalent brain growth spurt, which occurs from postnatal day
      (PD) 4 to 9, via oral intubation. Sham-intubated and nontreated controls were
      included. Subjects were treated with 100 mg/kg/d choline chloride or vehicle from
      PD 40 to 60, a period equivalent to young adulthood in the rat. After the choline
      treatment had ceased, subjects were tested on a series of behavioral tasks: open
      field activity (PD 61 to 64), Morris water maze spatial learning (PD 65 to 73),
      and spatial working memory (PD 87 to 91). RESULTS: Ethanol-exposed subjects were
      overactive in the activity chambers and impaired on both the spatial and the
      working memory versions of the Morris water maze. Choline treatment failed to
      attenuate alcohol-related overactivity in the open field and deficits in Morris
      water maze performance. In contrast, choline supplementation significantly
      mitigated alcohol-related deficits in working memory, which may suggest that
      choline administration at this later developmental time affects functioning of
      the prefrontal cortex. CONCLUSIONS: The results indicate that adolescent choline
      supplementation can attenuate some, but not all, of the behavioral deficits
      associated with early developmental alcohol exposure. The results of this study
      indicate that dietary intervention may reduce some fetal alcohol effects, even
      when administered later in life, findings with important implications for
      adolescents and young adults with fetal alcohol spectrum disorders.

PMID- 27038599
TI  - Oral Conditioned Cues Can Enhance or Inhibit Ethanol (EtOH)-Seeking and EtOH
      Relapse Drinking by Alcohol-Preferring (P) Rats.
AB  - BACKGROUND: Conditioned cues can elicit drug-seeking in both humans and rodents.
      The majority of preclinical research has employed excitatory conditioned cues
      (stimuli present throughout the availability of a reinforcer), but oral
      consumption of alcohol is similar to a conditional stimuli (presence of stimuli
      is paired with the delivery of the reinforcer) approach. The current experiments
      attempted to determine the effects of conditional stimuli (both excitatory and
      inhibitory) on the expression of context-induced ethanol (EtOH)-seeking. METHODS:
      Alcohol-preferring (P) rats self-administered EtOH and water in standard 2-lever
      operant chambers. A flavor was added to the EtOH solution (CS+) during the EtOH
      self-administration sessions. After 10 weeks, rats underwent extinction training
      (7 sessions), followed by a 2-week home cage period. Another flavor was present
      during extinction (CS-). Rats were exposed to a third flavor in a non-drug-paired
      environment (CS(0)). EtOH-seeking was assessed in the presence of no cue, CS+, CS
      , or CS(0) in the dipper previously associated with EtOH self-administration (no
      EtOH available). Rats were maintained a week in their home cage before being
      returned to the operant chambers with access to EtOH (flavored with no cue, CS+,
      CS-, or CS(0)). RESULTS: The results indicated that the presence of the CS+
      enhanced EtOH-seeking, while the presence of the CS- suppressed EtOH-seeking.
      Similarly, adding the CS- flavor to 15% EtOH reduced responding for EtOH while
      the CS+ enhanced responding for EtOH during relapse testing. CONCLUSIONS:
      Overall, the data indicate that conditional stimuli are effective at altering
      both EtOH-seeking behavior and EtOH-relapse drinking.

PMID- 27038600
TI  - Impact of silicon on Indian mustard (Brassica juncea L.) root traits by
      regulating growth parameters, cellular antioxidants and stress modulators under
      arsenic stress.
AB  - Arsenic (As) is an emerging pollutant causing inhibition in growth and
      development of plants resulting into phytotoxicity. On the other hand, silicon
      (Si) has been suggested as a modulator in abiotic and biotic stresses that,
      enhances plant's physiological adaptations in response to several stresses
      including heavy metal stress. In this study, we used roots of hydroponically
      grown 14 day old seedlings of Brassica juncea var. Varuna treated with 150 MUM
      As, 1.5 mM Si and both in combination for 96 h duration. Application of Si
      modulated the effect of As by improving morphological traits of root along with
      the development of both primary and lateral roots. Changes observed in root
      traits showed positive correlation with As induced cell death, accumulation of
      reactive oxygen species (ROS), nitric oxide (NO) and intracellular superoxide
      radicals (O2(-)). Addition of 1.5 mM Si during As stress increased accumulation
      of As in roots. Mineral nutrient analysis was done using energy-dispersive X-ray
      fluorescence (EDXRF) technique and positively correlated with increased cysteine,
      proline, MDA, H2O2 and activity of antioxidant enzymes (SOD, CAT and APX). The
      results obtained from the above biochemical approaches support the protective and
      active role of Si in the regulation of As stress through the changes in root
      developmental process. 

PMID- 27038601
TI  - Evaluation of a novel promoter from Populus trichocarpa for mature xylem tissue
      specific gene delivery.
AB  - Wood (i.e., secondary xylem) is an important raw material for many industrial
      applications. Mature xylem (MX) tissue-specific genetic modification offers an
      effective means to improve the chemical and physical properties of the wood.
      Here, we describe a promoter that drives strong gene expression in a MX tissue
      specific manner. Using whole-transcriptome genechip analyses of different tissue
      types of poplar, we identified five candidate genes that had strong expression in
      the MX tissue. The putative promoter sequences of the five MX-specific genes were
      evaluated for their promoter activity in both transgenic Arabidopsis and poplar.
      Among them, we found the promoter of Potri.013G007900.1 (called the PtrMX3
      promoter) had the strongest activity in MX and thus was further characterized. In
      the stem and root tissues of transgenic Arabidopsis plants, the PtrMX3 promoter
      activity was found exclusively in MX tissue. MX-specific activity of the promoter
      was reproduced in the stem tissue of transgenic poplar plants. The PtrMX3
      promoter activity was not influenced by abiotic stresses or exogenously applied
      growth regulators, indicating the PtrMX3 promoter is bona fide MX tissue
      specific. Our study provides a strong MX-specific promoter for MX-specific
      modifications of woody biomass. 

PMID- 27038602
TI  - Tomato plants acclimate better to elevated temperature and high light than to
      treatment with each factor separately.
AB  - The influence of two factors - high temperature and high light intensity, acting
      separately or simultaneously on the pigment composition, fluorescent
      characteristics, membrane integrity and synthesis of protective substances was
      investigated in tomato plants (Solanum lycopersicum cv. M 82). Moderate elevated
      temperatures (38/29  degrees C) were applied under optimum or high light
      intensity for 2 and 6 days and after that the plants are allowed to recover for 5
      days at optimum conditions. Parameters of chlorophyll fluorescence were used to
      evaluate the alterations of photosystem I and photosystem II activity and
      malondialdehyde content was determined as a measure of stress-induced
      peroxidation of membrane lipids. The response of treated plants to high light and
      elevated temperature was estimated by analyzing the accumulation of anthocyanins.
      Both stress factors exhibit different impact on studied parameters - high light
      intensity influences considerably quantum yield of photosystem II and
      photochemical quenching that is compensated to some extent when applied at
      elevated temperature. High temperature reduces strongly non-photochemical
      quenching. Data obtained show that after two days under particular conditions,
      the plants tend to acclimate, but this is achieved after longer treatment - 6
      days. During the recovery period the activity of photosystem I and the quantum
      yield of photosystem II recover almost completely, while the values of non
      photochemical quenching although slightly higher, did not reach the levels at the
      beginning of treatment. 

PMID- 27038603
TI  - Axonal degeneration, distal collateral branching and neuromuscular junction
      architecture alterations occur prior to symptom onset in the SOD1(G93A) mouse
      model of amyotrophic lateral sclerosis.
AB  - Degeneration of the distal axon and neuromuscular junction (NMJ) is considered a
      key and early feature of the pathology that accompanies motor neuron loss in
      people with amyotrophic lateral sclerosis (ALS). The mutant SOD1(G93A) mouse
      replicates many features of the disease, however the sequence of events resulting
      in degeneration of the neuromuscular circuitry remains unknown. Furthermore,
      despite widespread degenerative neuronal pathology throughout the spinal cord in
      this model, hindlimb motor function is lost before forelimb function. We
      investigated axons and NMJs in the hindlimb (gastrocnemius) and forelimb
      (extensor) muscles in the high copy number mutant SOD1(G93A)xYFP (yellow
      fluorescent protein) mouse. We found that distal axonal and NMJ alterations were
      present prior to previously reported functional symptom onset in this strain.
      Indeed, increased branch complexity as well as colocalisation between pre- and
      post-synaptic markers indicated widespread early axonal and NMJ alterations in
      the hindlimb. Immunohistochemical analysis demonstrated that the colocalisation
      of the scaffolding proteins nestin, LRP-4, dystrophin and rapsyn were diminished
      before post-synaptic receptors in the gastrocnemius, and the degree of loss
      differed between proteins. Analysis of the forelimb muscle revealed axonal and
      NMJ degeneration at a late, post symptomatic stage, as well as novel differences
      in NMJ morphology, with reduced complexity. Furthermore, post-synaptic
      scaffolding proteins were preserved in the forelimb compared with the hindlimb.
      Analysis of protein levels indicated an increase in LRP-4, dystrophin and rapsyn
      in post symptomatic skeletal muscle that may suggest ongoing attempts at repair.
      This study indicates that axonal and NMJ degeneration in the SOD1 model of ALS is
      a complex and evolving sequence of events. We provide evidence that YFP can
      detect morphological and plastic alterations in the SOD1(G93A) mouse, and that
      the pre- and post-synaptic integrity of the NMJ plays an important role in the
      pathogenic mechanisms of ALS.

PMID- 27038605
TI  - "Extroverted Cuff", a novel modification of the elephant trunk technique for
      distal anastomosis of ragged descending aorta.
AB  - BACKGROUND: The elephant trunk technique has been applied in various situations
      including distal aortic dissection, entire aortic replacement, proximal aortic
      aneurysm, proximal aortic dissection, and Marfan's syndrome. The elephant trunk
      technique remains a challenge in cardiac surgery. Here we report a modification
      of this surgical approach. CASE PRESENTATION: The "extroverted cuff" technique
      that we propose is a novel modification of the flanged technique for the elephant
      trunk construction. The technique consists in the graft extroversion which is
      than located inside the descending aorta. Then the distal anastomosis is
      constructed between the descending aorta and the circular free edge the external
      layer of the graft. Such a technique was successfully applied in a patient with
      type A aortic dissection undergoing modified elephant trunk technique, aortic
      arch replacement and Bentall operation. CONCLUSION: Such a modification seems
      suitable for aortic arch aneurysm with ragged descending thoracic aorta that
      minimizes bleeding from the distal anastomosis and potentially prevents distal
      embolization of atheromatous plaque.

PMID- 27038604
TI  - Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical
      implications of CDC25 overexpression and potential treatment strategies.
AB  - Alterations in the cell-cycle regulatory genes result in uncontrolled cell
      proliferation leading to several disease conditions. Cyclin-dependent kinases
      (CDK) and their regulatory subunit, cyclins, are essential proteins in cell-cycle
      progression. The activity of CDK is regulated by a series of phosphorylation and
      dephosphorylation at different amino acid residues. Cell Division Cycle-25
      (CDC25) plays an important role in transitions between cell-cycle phases by
      dephosphorylating and activating CDKs. CDC25B and CDC25C play a major role in
      G2/M progression, whereas CDC25A assists in G1/S transition. Different isomers of
      CDC25 expressions are upregulated in various clinicopathological situations.
      Overexpression of CDC25A deregulates G1/S and G2/M events, including the G2
      checkpoint. CDC25B has oncogenic properties. Binding to the 14-3-3 proteins
      regulates the activity and localization of CDC25B. CDC25C is predominantly a
      nuclear protein in mammalian cells. At the G2/M transition, mitotic activation of
      CDC25C protein occurs by its dissociation from 14-3-3 proteins along with its
      phosphorylation at multiple sites within its N-terminal domain. In this article,
      we critically reviewed the biology of the activation/deactivation of CDC25 by
      kinases/phosphatases to maintain the level of CDK-cyclin activities and thus the
      genomic stability, clinical implications due to dysregulation of CDC25, and
      potential role of CDC25 inhibitors in diseases. 

PMID- 27038606
TI  - Genetic heteroscedastic models for ordinal traits: application to sheep litter
      size.
AB  - BACKGROUND: Classical genetic canalization models, which accommodate the mean and
      variance of a trait separately, provide a flexible approach to take
      heteroscedasticity for continuous traits into account. However, this model is not
      appropriate for discrete traits. The aim of this work was to propose
      heteroscedastic threshold models suitable for the genetic analysis of ordinal
      data. METHODS: In order to first fit the mean and variance of ordinal traits
      separately, we extended the classical threshold model (TM) for discrete data by
      introducing non-genetic and genetic factors of heterogeneity on the variance of
      its underlying variable, which leads to a homothetic threshold model HTM and its
      alternative parameterization HTM' in which the thresholds of different
      individuals are linked by a homothetic-translation. Relaxing the constraint
      between the thresholds led us to propose an independent threshold model ITM that
      was more flexible than HTM' but required the estimation of more parameters. TM,
      HTM and ITM models were applied to study 19,671 records on litter size in Romane
      sheep. RESULTS: Both HTM and ITM were able to disentangle the link between the
      mean and variance that holds in the classical homoscedastic threshold model. The
      results obtained for the litter size of Romane ewes showed that the data was best
      fitted with HTM compared to ITM and TM. The correlations between the observed and
      predicted variances were equal to 0.6 and 0.2 for HTM and TM, respectively. These
      analyses showed the existence of a genetic component for the heterogeneity of
      litter size in sheep that was taken into account in HTM. CONCLUSIONS: HTM is the
      most suitable model to study the variability of litter size in sheep. It
      accommodates both the mean and variance separately while requiring the estimation
      of only a few parameters.

PMID- 27038607
TI  - Limited independent prognostic value of MMP-14 and MMP-2 expression in ovarian
      cancer.
AB  - BACKGROUND: In cancer, various MMPs play a role in progression and metastasis and
      their overexpression generally indicates a poor prognosis. MMP-14 is the main
      activator of MMP-2 and both molecules play a role in normal ovarian follicular
      development. Earlier reports indicated a prognostic value for both MMP-14 and MMP
      2 in ovarian cancer. This study was designed to determine the prognostic value of
      MMP-14 and MMP-2 expression in ovarian cancer with data on long-term follow-up.
      METHODS: Tumor samples of 94 consecutive ovarian cancer patients from one
      regional laboratory were evaluated. Clinical and survival data were collected and
      related to known prognostic factors, as well as to the expression of MMP-14 and
      MMP-2 as determined by semi-quantitative immunohistochemistry. RESULTS:
      Epithelial MMP-14 expression correlated with stromal MMP-14 expression (rho =
      .47, p < .01) and epithelial MMP-2 expression was found to correlate with both
      MMP-14 epithelial and stromal expression (rho = -.28, p < .01 respectively rho = 
      .21, p < .05). In univariable analysis of 64 advanced-staged tumours, no MMP
      parameter was significant for progression-free or overall survival. In
      multivariable analysis for PFS, stromal MMP-14 expression and epithelial MMP-2
      expression remained in the model. For overall survival, no MMP parameter showed
      significance. CONCLUSIONS: We confirmed the correlation between epithelial and
      stromal MMP-14 expression and between epithelial MMP-2 and both epithelial and
      stromal MMP-14 expression. In this study with long-term follow-up, the
      independent prognostic value of MMP-14 and MMP-2 expression in ovarian cancer is
      limited to a role in PFS for stromal MMP-14 expression and epithelial MMP-2
      expression.

PMID- 27038608
TI  - A phase III randomized study to evaluate the efficacy and safety of CT-P13
      compared with reference infliximab in patients with active rheumatoid arthritis:
      54-week results from the PLANETRA study.
AB  - BACKGROUND: CT-P13 (Remsima(r), Inflectra(r)) is a biosimilar of the infliximab
      reference product (RP; Remicade(r)). The aim of this study was to compare the 54
      week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics
      (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA). METHODS:
      In this multinational phase III double-blind study, patients with active RA and
      an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT
      P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54
      in combination with MTX (12.5-25 mg/week). Efficacy endpoints included American
      College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity
      Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical
      Disease Activity Index (CDAI), European League Against Rheumatism (EULAR)
      response rates, patient-reported outcomes and joint damage progression.
      Immunogenicity, safety and PK/PD outcomes were also assessed. RESULTS: Of 606
      randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week
      54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3
      %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13
      43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI
      and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and
      RP. Radiographic progression measured by Sharp scores as modified by van der
      Heijde was also comparable. With both treatments, patient assessments of pain,
      disease activity and physical ability, as well as mean scores on the Medical
      Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and
      remained stable thereafter up to week 54. The proportion of patients positive for
      antidrug antibodies at week 54 was similar between the two groups: 41.1 % and
      36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a
      similar safety profile to RP. PK/PD results were also comparable between CT-P13
      and RP. CONCLUSIONS: CT-P13 and RP were comparable in terms of efficacy
      (including radiographic progression), immunogenicity and PK/PD up to week 54. The
      safety profile of CT-P13 was also similar to that of RP. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01217086 . Registered 4 Oct 2010.

PMID- 27038609
TI  - What is the effect of sensory discrimination training on chronic low back pain? A
      systematic review.
AB  - BACKGROUND: Sensory discrimination training (SDT) for people with chronic low
      back pain (CLBP) is a novel approach based on theories of the cortical
      reorganization of the neural system. SDT aims to reverse cortical reorganization,
      which is observed in chronic pain patients. SDT is still a developing therapeutic
      approach and its effects have not been systematically reviewed. The aim of this
      systematic review was to evaluate if SDT decreases pain and improves function in
      people with CLBP. METHODS: A systematic review was performed on the available
      literature to evaluate the effects of SDT. Randomised controlled trials compared
      the effectiveness of SDT on pain and function in people with CLBP with the
      effectiveness of other physiotherapy interventions, no treatment, or sham
      therapy. The methodological quality of the included studies and the clinical
      relevance of reported treatment effects were investigated. RESULTS: The original
      search revealed 42 records of which 6 fulfilled the inclusion criteria. The
      majority of studies showed that SDT caused statistically significant improvements
      in pain and function, but only two studies reported clinically relevant
      improvements. The applied SDT varied considerably with regard to dosage and
      content. The methodological quality of the included studies also varied, which
      hampered the comparability of results. CONCLUSIONS: Although SDT seems to improve
      pain and function in people with CLBP, study limitations render firm conclusions
      unsafe. Future studies should pay closer attention to power and sample selection
      as well as to the content and dosage of the SDT intervention. We recommend a
      large, well-powered, prospective randomized control study that uses a
      standardized SDT approach to address the hypothesis that SDT causes clinically
      relevant improvements in pain and function.

PMID- 27038610
TI  - A proposal of linear assessment scheme for the udder of dairy camels (Camelus
      dromedarius L.).
AB  - Digital images from the left side of the mammary gland of 146 multiparous
      lactating dromedary camels in mid lactation and managed under intensive
      conditions were obtained immediately before milking and used to build up a
      reference scheme for the morphological evaluation of camel mammary glands. A 5
      point linear scoring scheme (with 0.5-point accuracy) was subsequently generated
      based on five mammary traits (udder, depth and floor inclination, teats, shape,
      length, and width). Results showed that Arabian dairy camels had voluminous
      udders with large-sized teats. Most common udder shape was globular (47.3 %),
      followed by the pear (34.3 %) and pendulous (18.4 %) shapes. Conical- or funnel
      shaped teats (60.9 %) were the most frequent, followed by cylindrical- (29.5 %)
      and blew-up (9.6 %)-shaped teats. The observed variation in the udder and teat
      measurements, as well as in typology, attested that dromedary camels need
      especially large milking clusters to improve their machine milkability.
      Assessment of the previously indicated digital images according to the proposed
      linear scoring scheme, performed by 3 independent operators showed that the
      overall means were close to 3.00 points (values between 2.45 and 3.62), and the
      standard deviations were close to 0.76 points (values between 0.58 and 0.94).
      Moderate repeatability between operators (r > 0.69) was obtained for udder depth
      and floor inclination, indicating that training of operators, as well as
      improvements in the definition of traits should be considered in future studies.
      Further research is needed to validate the proposed linear scoring system in
      different stages of lactation and parities using a large number of camels. 

PMID- 27038611
TI  - Effectiveness of pharmaceutical care for drug treatment adherence in patients
      with systemic lupus erythematosus in Rio de Janeiro, Brazil: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Treatment adherence is a primary determinant of the success and
      effectiveness of healthcare. Lack of adherence can lead to treatment failure and
      death. Although studies have shown that pharmaceutical intervention can improve
      drug treatment for patients with chronic diseases, studies on pharmaceutical care
      are not only inconsistent, they are scarce and limited to developed countries,
      include few patients, and are not studied in randomized clinical trials. Systemic
      lupus erythematosus is an autoimmune disease with high hospitalization and case
      fatality rates. The adherence rate is low (31.7 %) in this group of patients in
      Brazil, and drug treatment for the disease is complex. Our objective is to
      evaluate the effectiveness of pharmaceutical care in drug treatment adherence in
      patients with systemic lupus erythematosus treated at a rheumatology outpatient
      clinic in Rio de Janeiro, Brazil. METHODS: A randomized clinical trial (pragmatic
      trial) will be conducted. Adult participants (women) from a public hospital in
      Rio de Janeiro with a diagnosis of systemic lupus erythematosus will be followed
      for 12 months. A total of 120 patients will be randomized to two groups:
      intervention (Dader method for pharmaceutical care) and control (health/dietary
      counseling and risk reduction). The primary outcome will be drug treatment
      adherence evaluated by the eight-item Morisky Medication Adherence Scale.
      Secondary outcomes will be clinical improvement and quality of life. DISCUSSION:
      Patients with systemic lupus erythematosus present with low treatment adherence,
      thus justifying the mobilization of human resources to optimize their clinical
      management. Despite the proven effectiveness of pharmaceutical care for various
      diseases, there are still no studies evaluating its effectiveness in systemic
      lupus erythematosus. Our hypothesis is that the intervention will also be
      effective in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT02330250 .

PMID- 27038612
TI  - Molecular Cardiovascular Magnetic Resonance: Current Status and Future Prospects.
AB  - In the Western world and developing countries, the number one causes of mortality
      and morbidity result from cardiovascular diseases. Cardiovascular diseases
      represent a wide range of pathologies, including myocardial infarction,
      peripheral vascular disease, and cerebrovascular disease, which are all linked by
      a common cause - atherosclerosis. Currently, the diagnosis of atherosclerosis is
      in most cases established at the end stage of the disease, when patients are
      administered to the emergency room due to a myocardial infarction or stroke. Even
      though cardiovascular diseases have an enormous impact on society, there are
      still limitations in the early diagnosis and the prevention of the disease.
      Current imaging methods mainly focus on morphological changes that occur at an
      advanced disease stage, e.g., degree of stenosis. Cardiovascular magnetic
      resonance imaging and specifically molecular cardiovascular magnetic resonance
      imaging are capable to reveal pathophysiological changes already occurring during
      early atherosclerotic plaque formation. This allows for the assessment of
      cardiovascular disease on a level, which goes beyond morphological or anatomical
      criteria. In this review, we will introduce promising MR-based molecular imaging
      strategies for the non-invasive assessment of cardiovascular disease.

PMID- 27038613
TI  - Retinoblastoma in a pediatric oncology reference center in Southern Brazil.
AB  - BACKGROUND: Retinoblastoma (Rb) is the most common intraocular tumor diagnosed in
      children in Brazil. However, detailed information is lacking regarding patient
      clinical demographics. This study aimed to determine the clinical profile of
      patients with Rb who were treated in a public university hospital in southern
      Brazil from 1983 to 2012. METHODS: Patients' medical records were reviewed to
      retrospectively identify patients with a principal diagnosis of Rb. Rb was
      classified as hereditary or non-hereditary. Clinical staging was reviewed by an
      ophthalmologist. Statistical analysis was performed using SPSS. RESULTS: Of 165
      patients with a diagnosis of Rb during this period, 140 were included in the
      study. Disease was unilateral in 65.0 % of patients, bilateral in 32.9 %, and
      trilateral in 2.1 %. The mean age at onset of the first sign/symptom was 18.1
      month, and 35.7 % of patients were diagnosed during the first year of life. The
      most common presenting signs were leukocoria (73.6 %) and strabismus (20.7 %).
      The mean age at diagnosis was 23.5 months, and time to diagnosis was 5.4 months.
      In patients with clinical features of hereditary Rb, both onset of the first
      sign/symptom and diagnosis were at an earlier age than in patients without these
      features (12.3 vs 21.6 months [P = 0.001] and 15.9 vs 28.0 months [P < 0.001],
      respectively). However, there was no significant difference in overall survival
      between the two groups. Ocular stage at diagnosis was advanced in 76.5 % (Reese
      V) and 78.1 % (International Classification D or E). Of patients with unilateral
      and bilateral disease, 35.2 % and 34.8 %, respectively, had extraocular disease
      at diagnosis; 10.7 % had metastatic disease at diagnosis. Enucleation was
      observed in 88.1 % and exenteration in 11.9 % of patients; 93.6 % patients were
      followed until 2012, and 22.9 % relapsed. Overall survival was 86.4 %.
      CONCLUSIONS: Most Rb diagnoses are still diagnosed in advanced stages of the
      disease, considerably reducing overall survival time and the rate of eye and
      vision preservation.

PMID- 27038614
TI  - Multimodal perioperative care plus immunonutrition versus traditional care in
      total hip arthroplasty: a randomized pilot study.
AB  - BACKGROUND: Multimodal protocols of perioperative care may enhance postoperative
      recovery. However, limited information is available on preoperative immune and
      carbohydrate (CHO)-enriched drinks in patients undergoing hip arthroplasty. We
      aimed to investigate the effect of a multimodal protocol (ACERTO protocol) plus
      preoperative immune nutrition on the length of stay (LOS) and the postoperative
      acute phase response of patients undergoing total hip arthroplasty. METHODS:
      Thirty-two patients (mean age, 58 years; range, 26-85 years; 16 males) were
      randomized to receive either the ACERTO protocol (n = 15, ACERTO Group), which
      consisted of 6 h preoperative fasting for solids, an oral drink (200 mL of 12.5 %
      maltodextrin) up to 2 h before induction of anesthesia, restricted intravenous
      fluids (only 1000 mL of crystalloid fluid after surgery) and preoperative immune
      nutrition (600 mL/day of Impact - Nestle, Brazil) for five days prior to surgery,
      or traditional care (n = 17; control group), which consisted of 6-8 h
      preoperative fasting, intravenous hydration until the 1(st) postoperative day and
      no preoperative immune supplementation. The main endpoint was LOS. C-reactive
      protein (CRP) was the secondary endpoint and was assessed during induction of
      anesthesia and on postoperative day 2. RESULTS: Neither deaths nor postoperative
      complications occurred. The median LOS was 3 (2-5) days in the ACERTO group and 6
      (3-8) days in controls (P <0.01). Postoperative CRP was higher in the control
      group (P <0.01). CONCLUSION: The ACERTO multimodal protocol of perioperative care
      plus preoperative immune nutrition may decrease LOS and postoperative CRP levels
      in total hip arthroplasty. TRIAL REGISTRATION:  CLINICAL TRIALS: NCT02580214.

PMID- 27038615
TI  - 25 years on and no end in sight: a perspective on the role of RecG protein.
AB  - The RecG protein of Escherichia coli is a double-stranded DNA translocase that
      unwinds a variety of branched substrates in vitro. Although initially associated
      with homologous recombination and DNA repair, studies of cells lacking RecG over
      the past 25 years have led to the suggestion that the protein might be multi
      functional and associated with a number of additional cellular processes,
      including initiation of origin-independent DNA replication, the rescue of stalled
      or damaged replication forks, replication restart, stationary phase or stress
      induced 'adaptive' mutations and most recently, naive adaptation in CRISPR-Cas
      immunity. Here we discuss the possibility that many of the phenotypes of recG
      mutant cells that have led to this conclusion may stem from a single defect,
      namely the failure to prevent re-replication of the chromosome. We also present
      data indicating that this failure does indeed contribute substantially to the
      much-reduced recovery of recombinants in conjugational crosses with strains
      lacking both RecG and the RuvABC Holliday junction resolvase.

PMID- 27038616
TI  - Unravel biophysical factors on river water quality response in Chilean Central
      Southern watersheds.
AB  - Identifying the key anthropogenic (land uses) and natural (topography and
      climate) biophysical drivers affecting river water quality is essential for
      efficient management of water resources. We tested the hypothesis that water
      quality can be predicted by different biophysical factors. Multivariate
      statistics based on a geographical information system (GIS) were used to explore
      the influence of factors (i.e., precipitation, topography, and land uses) on
      water quality (i.e., nitrate (NO 3 (-)), phosphate (PO 4 (3-)), silicate
      (Si(OH)4), dissolved oxygen (DO), suspended solids (TSS), biological oxygen
      demand (DO), temperature (T), conductivity (EC), and pH) for two consecutive
      years in the Itata and Biobio river watersheds, Central Chile (36 degrees  00'
      and 38 degrees  30'). The results showed that (NO 3 (-)), (PO 4 (3-)), Si(OH)4,
      TSS, EC, and DO were higher during rainy season (austral fall, winter, and
      spring), whereas BOD and temperature were higher during dry season. The spatial
      variation of these parameters in both watersheds was related to land use,
      topography (e.g., soil moisture, soil hydrological group, and erodability), and
      precipitation. Soil hydrological group and soil moisture were the strongest
      explanatory predictors for PO 4 (3-) , Si(OH)4 and EC in the river, followed by
      land use such as agriculture for NO 3 (-) and DO and silviculture for TSS and
      Si(OH)4. High-resolution water leaching and runoff maps allowed us to identify
      agriculture areas with major probability of water leaching and higher probability
      of runoff in silviculture areas. Moreover, redundancy analysis (RDA) revealed
      that land uses (agriculture and silviculture) explained in 60 % the river water
      quality variation. Our finding highlights the vulnerability of Chilean river
      waters to different biophysical drivers, rather than climate conditions alone,
      which is amplified by human-induced degradation.

PMID- 27038617
TI  - Speaking valves in tracheostomised ICU patients weaning off mechanical
      ventilation--do they facilitate lung recruitment?
AB  - BACKGROUND: Patients who require positive pressure ventilation through a
      tracheostomy are unable to phonate due to the inflated tracheostomy cuff. Whilst
      a speaking valve (SV) can be used on a tracheostomy tube, its use in ventilated
      ICU patients has been inhibited by concerns regarding potential deleterious
      effects to recovering lungs. The objective of this study was to assess end
      expiratory lung impedance (EELI) and standard bedside respiratory parameters
      before, during and after SV use in tracheostomised patients weaning from
      mechanical ventilation. METHODS: A prospective observational study was conducted
      in a cardio-thoracic adult ICU. 20 consecutive tracheostomised patients weaning
      from mechanical ventilation and using a SV were recruited. Electrical Impedance
      Tomography (EIT) was used to monitor patients' EELI. Changes in lung impedance
      and standard bedside respiratory data were analysed pre, during and post SV use.
      RESULTS: Use of in-line SVs resulted in significant increase of EELI. This effect
      grew and was maintained for at least 15 minutes after removal of the SV (p <
      0.001). EtCO2 showed a significant drop during SV use (p = 0.01) whilst SpO2
      remained unchanged. Respiratory rate (RR (breaths per minute)) decreased whilst
      the SV was in situ (p <0.001), and heart rate (HR (beats per minute)) was
      unchanged. All results were similar regardless of the patients' respiratory
      requirements at time of recruitment. CONCLUSIONS: In this cohort of critically
      ill ventilated patients, SVs did not cause derecruitment of the lungs when used
      in the ventilator weaning period. Deflating the tracheostomy cuff and restoring
      the airflow via the upper airway with a one-way valve may facilitate lung
      recruitment during and after SV use, as indicated by increased EELI. TRIAL
      REGISTRATION: Anna-Liisa Sutt, Australian New Zealand Clinical Trials Registry
      (ANZCTR). ACTRN: ACTRN12615000589583. 4/6/2015.

PMID- 27038618
TI  - How do case managers spend time on their functions and activities?
AB  - BACKGROUND: Case management has been a widely accepted approach to practice in
      various care settings. This study aimed to explore how community aged care case
      managers allocated their time to case management functions, how frequently they
      performed specific case management activities, and what factors influenced the
      frequency of their activities. METHODS: The study involved 154 survey
      participants, or 17.1% of the target case managers in the State of Victoria,
      Australia. Key information collected included participants' socio-demographic
      characteristics, proportions of time allocated to six core case management
      functions, and frequency ratings of 41 specific activities within seven case
      management functions. Ordinal regression analyses were performed to determine
      significant factors associated with participants' frequency ratings of their
      activities. RESULTS: Participants allocated the largest proportion of time to
      care coordination (22.0%), and the smallest proportion of time to outcome
      evaluation (8.0%). Over 70% of the participants assigned high frequency ratings
      to 31 of the 41 case management activities. The remaining ten activities,
      including all four outcome evaluation activities, three needs assessment
      activities, one care planning activity, one care coordination activity, and one
      general functions-related activity were less commonly performed very frequently.
      The regression analyses indicated that some case manager and client factors were
      significantly associated with frequency ratings of nine of the ten activities
      aforementioned. The two main findings of the regression analyses were: First,
      emphasising achieving more case management goals was significantly associated
      with higher frequency of three outcome evaluation activities; second, longer work
      experience was significantly associated with higher frequency of one care
      coordination activity and one outcome evaluation activity. CONCLUSIONS: The
      frequent performance of most case management activities and relative absence of
      factors influencing their frequency suggest a uniformity of practice in community
      aged care case managers' practice. What is not clear is whether the frequency of
      these activities (in particular less frequent performance of outcome evaluation
      activities) conforms to expectations.

PMID- 27038619
TI  - Drimane Sesquiterpenoids and Isochromone Derivative from the Endophytic Fungus
      Pestalotiopsis sp. M-23.
AB  - Three new drimane sesquiterpenoids (1-3) together with the known 2alpha
      hydroxyisodrimeninol (4), and a new isochromone derivative (5), were obtained
      from the solid cultures of fungal strain Pestalotiopsis sp. M-23, an endophytic
      fungus isolated from the leaves of Leucosceptrum canum (Labiatae). Their
      structures were determined by comprehensive 1D and 2D NMR, and MS analyses. The
      metabolites were evaluated for their antibacterial activities, and compound 3
      showed weak inhibitory activity against Bacillus subtilis. 

PMID- 27038620
TI  - Analytical Assessment of Bio- and Toxic Elements Distribution in Pu-erh and Fruit
      Teas in View of Chemometric Approach.
AB  - This study concerns application of flame atomic absorption spectrometry (FAAS) in
      assessment of macro- and microelement and toxic metal levels (Mg, Ca, K, Na, Mn,
      Cu, Fe, Zn, Cr, Ni, Co, Cd and Pb) in dark (Pu-erh) and fruit tea leaves and
      their infusions. Phosphorus was also determined in the form of phosphomolybdate
      by spectrophotometric method. The reliability of the method was checked using
      three certified reference materials. The results of analysis were in agreement
      with the certified values, with analytical recovery ranging from 86 to 113 %.
      Significant correlations (p < 0.001) were found between concentrations of P, Zn,
      K, Ni, Fe, Co, Cr, and Pb in Pu-erh tea, whereas in fruit tea, such
      interdependences were found between Mg, Fe, P, Ni, and Co. Kruskal-Wallis test
      results have related differences in Pu-erh tea quality as well as technological
      processing of fruit tea to their mineral composition. In order to characterize
      tea elemental content, chemometric techniques such as factor analysis (FA) and
      cluster analysis (CA) were used. Their application allowed on differentiation of
      samples in view of the fermentation type, technological processing, and overall
      quality.

PMID- 27038621
TI  - Protective Role of Zinc and Magnesium against Cadmium Nephrotoxicity in Male
      Wistar Rats.
AB  - Cd is a toxic metal that has a destructive impact on most organ systems. This
      work aims to determine Zn or Mg protective effects against Cd renal toxicity. In
      this study, rats were divided into six groups. The Cd group was treated with 1 mg
      Cd/kg, and the control group received 0.5 cm3 normal saline, intraperitoneally.
      The other four groups received one of the following dosages of 1 mg/kg Cd + 0.5
      mg/kg Zn, 1 mg/kg Cd + 1.5 mg/kg Zn, 1 mg/kg Cd + 0.5 mg/kg Mg, or 1 mg/kg Cd +
      1.5 mg/kg Mg through IP injection for 3 weeks. Kidney malondialdehyde (MDA) and
      serum sodium, potassium, urea, creatinine, and protein were measured. Light
      microscopic examination was used for histological studies. Cd reduced serum
      creatinine and protein, and increased urea, sodium, and potassium. Moreover, Cd
      exposure caused a significant enhancement in MDA levels as well as histological
      damage in kidneys. Zn or Mg treatment prevented and reversed toxic alterations
      induced by Cd. These results suggest that Zn and Mg may have protective effects
      against Cd renal toxicity.

PMID- 27038622
TI  - Cerium Oxide-Incorporated Calcium Silicate Coating Protects MC3T3-E1 Osteoblastic
      Cells from H2O2-Induced Oxidative Stress.
AB  - Oxidative stress regulates cellular functions in multiple pathological
      conditions, including bone formation by osteoblastic cells. In this work, the
      protective effects of cerium oxide (CeO2)-incorporated calcium silicate (CeO2-CS)
      coating on the response of osteoblasts to H2O2-induced oxidative stress and the
      related mechanism were examined. CeO2 incorporation significantly improved
      osteoblast viability and reduced cell apoptosis caused by H2O2 when compared with
      the control. H2O2-induced reduction of differentiation marker alkaline
      phosphatase (ALP) was recovered in the presence of the CeO2-CS coating. The above
      effects were mediated by the antioxidant effect of CeO2. The CeO2-CS coating
      immersed in 0.1 mM H2O2 aqueous solution was able to degrade 64 % of it in 1
      week. In addition, CeO2 incorporation decreased reactive oxygen species (ROS)
      production and suppressed malondialdehyde (MDA) formation in H2O2-treated
      osteoblasts. Taken together, CeO2-CS biomedical coatings with antioxidant
      property would be promising for bone regeneration under oxidative stress.

PMID- 27038623
TI  - Transcriptome dynamics in the asexual cycle of the chordate Botryllus schlosseri.
AB  - BACKGROUND: We performed an analysis of the transcriptome during the
      blastogenesis of the chordate Botryllus schlosseri, focusing in particular on
      genes involved in cell death by apoptosis. The tunicate B. schlosseri is an
      ascidian forming colonies characterized by the coexistence of three blastogenetic
      generations: filter-feeding adults, buds on adults, and budlets on buds.
      Cyclically, adult tissues undergo apoptosis and are progressively resorbed and
      replaced by their buds originated by asexual reproduction. This is a feature of
      colonial tunicates, the only known chordates that can reproduce asexually.
      RESULTS: Thanks to a newly developed web-based platform (
      http://botryllus.cribi.unipd.it ), we compared the transcriptomes of the mid
      cycle, the pre-take-over, and the take-over phases of the colonial blastogenetic
      cycle. The platform is equipped with programs for comparative analysis and allows
      to select the statistical stringency. We enriched the genome annotation with
      11,337 new genes; 581 transcripts were resolved as complete open reading frames,
      translated in silico into amino acid sequences and then aligned onto the non
      redundant sequence database. Significant differentially expressed genes were
      classified within the gene ontology categories. Among them, we recognized genes
      involved in apoptosis activation, de-activation, and regulation. CONCLUSIONS:
      With the current work, we contributed to the improvement of the first released B.
      schlosseri genome assembly and offer an overview of the transcriptome changes
      during the blastogenetic cycle, showing up- and down-regulated genes. These
      results are important for the comprehension of the events underlying colony
      growth and regression, cell proliferation, colony homeostasis, and competition
      among different generations.

PMID- 27038624
TI  - Exploring the determinants of endocrinologist visits by patients with diabetes.
AB  - BACKGROUND: Diabetes is today a major public health concern in terms of its
      financial and social burden. Previous studies have revealed that specialist care
      for patients with diabetes leads to more positive outcomes than care by general
      practitioners (GPs) alone. The aim of this study was to estimate the determinants
      of endocrinologist consultation by patients with diabetes. METHODS: We used a two
      part model to explore both the decision to consult and the frequency of
      consultations. We used claim data collected for 65,633 affiliates of a French
      social security provider. Patients were aged over 18 and treated for diabetes
      (types I and II). We controlled for patients' socioeconomic characteristics, type
      of diabetes treatment, medical care, and health status. We also controlled for
      variables, such as the cost of a visit, the distance to the nearest
      endocrinologist's office, the density of medical practitioners and the prevalence
      of diabetes in the area. RESULTS: The results show that the parameters associated
      with the decision to consult an endocrinologist were considerably different from
      factors associated with the frequency of consultations. A marked positive effect
      of income on the decision to consult was found, whereas travel time to the office
      had a negative impact on both the decision to consult and the frequency of
      consultations. Increasing treatment complexity is associated with a higher
      probability of consulting an endocrinologist. We found evidence of a significant
      substitution effect between GPs and endocrinologists. Finally, consultation price
      is a barrier to seeing an endocrinologist. CONCLUSION: Given that financial
      barriers were identified in the relatively wealthy population analysed here, it
      is likely that this may be even more of an obstacle in the general population.

PMID- 27038625
TI  - Social/economic costs and health-related quality of life in patients with
      Duchenne muscular dystrophy in Europe.
AB  - OBJECTIVE: The aim of this study was to determine the economic burden from a
      societal perspective and the health-related quality of life (HRQOL) of patients
      with Duchenne muscular dystrophy (DMD) in Europe. METHODS: We conducted a cross
      sectional study of patients with DMD from Bulgaria, France, Germany, Hungary,
      Italy, Spain, Sweden, and the UK. Data on demographic characteristics, healthcare
      resource utilization, informal care, labor productivity losses, and HRQOL were
      collected from the questionnaires completed by patients or their caregivers.
      HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. Costs have
      been estimated from a societal perspective adopting a bottom-up approach.
      RESULTS: A total of 422 questionnaires were included in the study; 268 of which
      were collected from patients with DMD and 154 from caregivers. The average annual
      cost per person in 2012 ranged from ?7657 in Hungary to ?58,704 in France. Direct
      non-healthcare costs are the main component of whole costs and informal care is
      the main driver of non-healthcare costs. Costs are also shown to differ between
      children and adults. With regard to HRQOL of adult patients, the EQ-5D VAS score
      and EQ-5D index scores were 50.5 and 0.24, respectively. The corresponding EQ-5D
      VAS and EQ-5D index scores for caregivers were 74.7 and 0.71, respectively.
      CONCLUSIONS: We have estimated the average annual cost per patient with DMD in
      eight European countries adopting a social perspective, and to our knowledge this
      is the first study with such a wide perspective. The results on costs show a
      considerable gap between Eastern and Western European countries. Non-healthcare
      costs range from 64 to 89 % of overall costs and informal care is to a great
      extent the main driver of this cost category. The HRQOL of people with DMD is
      much lower than that of the general population.

PMID- 27038626
TI  - Social/economic costs and health-related quality of life in patients with
      scleroderma in Europe.
AB  - OBJECTIVE: The aim of this study was to determine the economic burden from a
      societal perspective and the health-related quality of life (HRQOL) of patients
      with systemic sclerosis (SSc; scleroderma) in Europe. METHODS: We conducted a
      cross-sectional study of patients with SSc (involving both localised and systemic
      sclerosis) from Germany, Italy, Spain, France, the UK, Hungary and Sweden. Data
      on demographic characteristics, healthcare resource utilisation, informal care,
      labour productivity losses and HRQOL were collected from the questionnaires
      completed by patients or their caregivers. HRQOL was measured with the EuroQol 5
      domain (EQ-5D) questionnaire. RESULTS: A total of 589 patients completed the
      questionnaire. The rate of patients with localised scleroderma, limited cutan and
      diffuse cutan SSc were 28, 68 and 4 %, respectively. Average annual costs varied
      from country to country and ranged from ? 4607 to ? 30,797 (reference year:
      2012). Estimated direct healthcare costs ranged from ? 1413 to ? 17,300; direct
      non-healthcare costs ranged from ? 1875 to ? 4684 and labour productivity losses
      ranged from ? 1701 to ? 14,444. The mean EQ-5D index score for adult SSc patients
      varied from 0.49 to 0.75 and the mean EQ-5D visual analogue scale score was
      between 58.72 and 65.86. CONCLUSION: The main strengths of this study lie in our
      bottom-up approach to costing and our evaluation of SSs patients from a broad
      societal perspective. This type of analysis is very unusual in the international
      literature on rare diseases in comparison with other illnesses. We concluded that
      SSc patients incur considerable societal costs and experience substantial
      deterioration in HRQOL.

PMID- 27038627
TI  - Social/economic costs and health-related quality of life in patients with Prader
      Willi syndrome in Europe.
AB  - OBJECTIVE: The aim of this study was to determine the economic burden from a
      societal perspective and health-related quality of life (HRQOL) of patients with
      Prader-Willi syndrome (PWS) in Europe. METHODS: We conducted a cross-sectional
      study of patients with PWS from Spain, Bulgaria, Hungary, Germany, Italy, the UK,
      Sweden and France. Data on demographic characteristics, healthcare resource
      utilisation, informal care, labour productivity losses and HRQOL were collected
      from questionnaires completed by patients or their caregivers. HRQOL was measured
      with the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: A total of 261 patients
      completed the questionnaire. The average annual costs ranged from ? 3937 to ?
      67,484 between countries; the reference year for unit prices was 2012. Direct
      healthcare costs ranged from ? 311 to ? 18,760, direct non-healthcare costs
      ranged from ? 1269 to ? 44,035, and loss of labour productivity ranged from ? 0
      to ? 2255. Costs were also shown to differ between children and adults. The mean
      EQ-5D index score for adult PWS patients ranged between 0.40 and 0.81 and the
      mean EQ-5D visual analogue scale score ranged between 51.25 and 90.00.
      CONCLUSION: The main strengths of this study lie in our bottom-up approach to
      costing and in the evaluation of PWS patients from a broad societal perspective.
      This type of analysis is very scarce in the international literature on rare
      diseases in comparison with other illnesses. We conclude that PWS patients incur
      considerable societal costs and experience substantial deterioration in HRQOL.

PMID- 27038628
TI  - Condensation Product of Phenylalanine and Salicylaldehyde: Fluorescent Sensor for
      Zn(2.).
AB  - The condensation product of phenylalanine and salicylaldehyde (L) was synthesised
      and characterised which was found to be selective fluorescent "off-on" sensor for
      Zn(2+) ion with the detection limit 10(-5) M. The sensor is free of interferences
      from metal ions - Na(+), K(+), Al(3+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Pb(2+),
      Cd(2+) and Hg(2+). The Fluorescence and the UV/visible spectral data reveals a
      1:1 interaction between the sensor and Zn(2+) ion with binding constant 10(8).
      The DFT and TDDFT calculations confirm the structures of the sensor and the
      sensor-Zn(2+) complex. 

PMID- 27038630
TI  - Stepwise discriminant function analysis for rapid identification of acute
      promyelocytic leukemia: should this be the first choice to establish the
      diagnosis of APL?

PMID- 27038629
TI  - The impact of preventive measures on the burden of femoral fractures - a
      modelling approach to estimating the impact of fall prevention exercises and oral
      bisphosphonate treatment for the years 2014 and 2025.
AB  - BACKGROUND: Due to the demographic transition with a growing number of old and
      oldest-old persons the absolute number of fragility fractures is expected to
      increase in industrialized countries unless effective preventive efforts are
      intensified. The main causes leading to fractures are osteoporosis and falls. The
      aim of this study is to develop population based models of the potential impact
      of fall-prevention exercise and oral bisphosphonates over the coming decade.
      METHODS: The German federal state of Bavaria served as the model population.
      Model interventions were limited to community-dwelling persons aged 65 years and
      older. Models are based on fall-prevention exercise being offered to all persons
      aged 70 to 89 years and oral bisphosphonate treatment offered to all persons with
      osteoporosis as defined by a T-score of <= - 2.5. Treatment effect sizes are
      estimated from meta-analyses. Reduction in all femoral fractures in the
      population of community-dwelling persons aged 65 years and older is the outcome
      of interest. A spreadsheet-based modelling approach was used for prediction.
      RESULTS: In 2014, reduction of femoral fractures by 10 % required 21 % of all
      community-dwelling persons aged 70-89 to participate in fall-prevention exercise,
      or 37 % of those with osteoporosis to receive oral bisphosphonates. Without
      intervention, demographic changes will result in a 24 % increase in femoral
      fractures by 2025. To lower the increase of fractures between 2014 and 2025 to 10
      %, fall-prevention-exercise participation rate needs to be 25 % and
      bisphosphonate treatment rates 41 %, whereas to hold the 2025 rates flat at 2014
      rates require 43 % fall-prevention-exercises participation, and is not achievable
      using oral bisphosphonates. CONCLUSIONS: Unrealistic high treatment and
      participation rates of the two analysed measures are needed to achieve
      substantial effects on the expected burden of femoral fractures at present and in
      the future.

PMID- 27038631
TI  - Pediatric radiology: current status and perspectives.

PMID- 27038632
TI  - Transcranial direct current stimulation of the prefrontal cortex reduces cue
      reactivity in alcohol-dependent patients.
AB  - Alcohol craving has been shown to be an important factor for relapses in alcohol
      dependent patients. Furthermore, brain activity in reward-related areas in
      response to alcohol-related cues is positively related to the amount of post
      relapse alcohol consumption. On the other hand, it has been shown that cue
      exposure based extinction training (CET) leads to larger decrease of striatal and
      left dorsolateral prefrontal cortex (dLPFC) cue-induced activation compared to
      standard clinical day-care treatment, but the effect sizes are relatively small.
      The question of this study was, whether it is possible to change cue-reactivity
      and subjective craving by applying bilateral prefrontal transcranial direct
      current stimulation (tDCS). We stimulated 30 detoxified alcohol-dependent
      patients (50 % with a sham and 50 % with left cathodal/right anodal stimulation)
      and presented emotional as well as alcohol-related pictures. We measured the
      emotional startle modulation and found significantly increased startle amplitudes
      in the verum stimulation condition for alcohol-related cues, indicating a more
      negative processing of this cues in alcohol-dependent patients after verum tDCS
      stimulation. Additionally we found tendencies for stronger reduction in
      subjective craving in verum-stimulated patients. Therefore our study underscores
      the positive value of DCS in reducing craving and might help to improve the
      understanding and therapy of alcohol dependence.

PMID- 27038633
TI  - The Columbian Exchange as a source of adaptive introgression in human
      populations.
AB  - BACKGROUND: The term "Columbian Exchange" refers to the massive transfer of life
      between the Afro-Eurasian and American hemispheres that was precipitated by
      Columbus' voyage to the New World. The Columbian Exchange is widely appreciated
      by historians, social scientists and economists as a major turning point that had
      profound and lasting effects on the trajectory of human history and development.
      PRESENTATION OF THE HYPOTHESIS: I propose that the Columbian Exchange should also
      be appreciated by biologists for its role in the creation of novel human genomes
      that have been shaped by rapid adaptive evolution. Specifically, I hypothesize
      that the process of human genome evolution stimulated by the Columbian Exchange
      was based in part on selective sweeps of introgressed haplotypes from ancestral
      populations, many of which possessed pre-evolved adaptive utility based on
      regional-specific fitness and health effects. TESTING THE HYPOTHESIS: Testing of
      this hypothesis will require comparative analysis of genome sequences from
      putative ancestral source populations, with genomes from modern admixed
      populations, in order to identify ancestry-specific introgressed haplotypes that
      exist at higher frequencies in admixed populations than can be expected by chance
      alone. Investigation of such ancestry-enriched genomic regions can be used to
      provide clues as to the functional roles of the genes therein and the selective
      forces that have acted to increase their frequency in the population.
      IMPLICATIONS OF THE HYPOTHESIS: Critical interrogation of this hypothesis could
      serve to underscore the important role of introgression as a source of adaptive
      alleles and as a driver of evolutionary change, and it would highlight the role
      of admixture in facilitating rapid human evolution.

PMID- 27038634
TI  - Sharing all types of clinical data and harmonizing journal standards.
AB  - Despite recent efforts to enforce policies requiring the sharing of data
      underlying clinical findings, current policies of biomedical journals remain
      largely heterogeneous. As this heterogeneity does not optimally serve the cause
      of data sharing, a first step towards better harmonization would be the
      requirement of a data sharing statement for all clinical studies and not simply
      for randomized studies. Although the publication of a data sharing statement does
      not imply that all data is made readily available, such a policy would swiftly
      implement a cultural change in the definition of scientific outputs. Currently, a
      scientific output only corresponds to a study report published in a medical
      journal, while in the near future it might consist of all materials described in
      the manuscript, including all relevant raw data. When such a cultural shift has
      been achieved, the logical conclusion would be for biomedical journals to require
      authors to make all data fully available without restriction as a condition for
      publication. 

PMID- 27038635
TI  - Metallothionein 2 and Heat Shock Protein 72 Protect Allolobophora chlorotica from
      Cadmium But Not Nickel or Copper Exposure: Body Malformation and Coelomocyte
      Functioning.
AB  - Earthworms serve as good indicators of heavy metal contamination due to their
      innate sensitivity towards soil pollution. However, to date, not many studies
      have focused on endogeic earthworms, such as the omnipresent Allolobophora
      chlorotica. The current study was designed to verify whether this earthworm could
      serve as a novel distinctively susceptible species for environmental
      contamination studies. We show that the dermal exposure to Cu, Ni, and Cd
      affected the mortality and morphology of A. chlorotica, and the number and
      functioning of coelomocytes. These features particularly were pronounced in
      animals treated with Ni and Cu and interestingly to a lesser extend with Cd. In
      contrast, Cd induced a strong expression of metallothioneins (MT-2) and heat
      shock proteins (HSP72). The presence of MT-2 was detected not only in
      coelomocytes but also in the intestine, blood vessels, and epidermis. In
      conclusion, Allolobophora chlorotica coelomocytes are adopted to respond
      differentially to various heavy metals, generating powerful response towards
      potentially most dangerous exogenous non-essential elements. 

PMID- 27038636
TI  - Erratum to: Induction of initial steps of angiogenic differentiation and
      maturation of endothelial cells by pericytes in vitro and the role of collagen
      IV.

PMID- 27038637
TI  - Rhabdomyosarcoma masquerading as lymphadenopathy in a patient with newly
      diagnosed Hodgkin's lymphoma.
AB  - BACKGROUND: Hodgkin's lymphoma (HL) is a rare malignancy which often presents
      with lymphadenopathy and classic "B symptoms" of weight loss, fever, and night
      sweats. Additional masses or nodes could easily be presumed to be a result of the
      initial diagnosis. On the other hand, adult rhabdomyosarcoma is a rare malignancy
      presenting with a new mass in a patient with previous diagnosis of Hodgkin's
      lymphoma. In both cases, a tissue diagnosis should be obtained to appropriately
      confirm the diagnosis. CASE PRESENTATION: We present a case of a 64-year-old male
      who presents with right axillary lymphadenopathy, diagnosed as Hodgkin's
      lymphoma. He subsequently developed left inguinal lymphadenopathy without the
      classic B symptoms of HL. Excisional biopsy revealed rhabdomyosarcoma. Stage III
      Hodgkin's lymphoma (lymph node involvement on both sides of the diaphragm) is not
      commonly seen without typical B symptoms. Once the diagnosis of two primary
      malignancies is made, the dilemma becomes determining the treatment course. In
      the case of Hodgkin's lymphoma and rhabdomyosarcoma, there is some overlap in the
      chemotherapeutic regimen and use of radiation. CONCLUSIONS: This case illustrates
      the importance of careful examination of Hodgkin's lymphoma patients and
      consideration of additional tissue diagnoses in atypical presentations of new
      masses or lymphadenopathy on the opposite side of the diaphragm.

PMID- 27038638
TI  - Repurposing of FDA-approved drugs against cancer - focus on metastasis.

PMID- 27038639
TI  - The Use of Patient-reported Outcomes in Demonstrating Safety and Efficacy in
      Oncology.

PMID- 27038640
TI  - Prognosis of Low Normal Left Ventricular Ejection Fraction in an Asymptomatic
      Population-Based Adult Cohort: The Multiethnic Study of Atherosclerosis.
AB  - BACKGROUND: Reduced left ventricular systolic function predicts worse outcomes.
      However, the optimal threshold for "normal" left ventricular ejection fraction
      (LVEF) is uncertain. In general, LVEF >= 55% is considered to be "normal" by
      guidelines, with a low normal designation for LVEF being 50%-55%. We assessed the
      prognosis of participants with low normal LVEF in the Multiethnic Study of
      Atherosclerosis. All participants were asymptomatic and had no known clinical
      cardiovascular disease at baseline. METHODS AND RESULTS: A total of 4926 out of
      6814 had LVEF assessed with the use of cardiac magnetic resonance imaging (MRI),
      had no significant valvular disease, did not have myocardial infarction during
      follow-up, had complete data, and were included in this analysis. A total of
      83/4926 (1.7%) had LVEF < 50% (low LVEF) and 101/4926 (2.1%) had low normal LVEF.
      Cox proportional hazard and cubic spline analyses were used to evaluate the
      association between LVEF category and 10 years of adjudicated incident congestive
      heart failure (CHF) and all-cause mortality adjusting for (model 1) age, sex, and
      race and (model 2) model 1 and diabetes mellitus, smoking, systolic blood
      pressure (BP), BP medications, body mass index, estimated glomerular filtration
      rate, low-density lipoprotein, family history of coronary heart disease,
      educational status, and LV mass. Mean age was 61 +/- 10 years, 47% were men, 35%
      were on BP medications, 9% had diabetes. After 10.2 years of follow-up, 109
      (2.2%) had CHF and 427 (8.7%) died. Compared with normal LVEF (>=55%), low normal
      LVEF and low LVEF were associated with an increased risk for incident CHF during
      follow-up in our multivariable Cox models: hazard ratios (HRs) 3.64 (95% CI 1.76
      7.52) and 9.52 (5.63-17.52), respectively. Unlike low LVEF, low normal LVEF was
      not associated with increased risk of death compared with normal LVEF in our
      fully adjusted models: HRs 3.03 (1.94-4.73) and 1.32 (0.72-2.41), respectively.
      In the adjusted spline analysis HR of LVEF 55% as reference, LVEF had a U-shape
      association of future CHF risk and LVEF. CONCLUSION: Low normal LVEF is as
      prevalent as low LVEF in asymptomatic community-dwelling adults. We observed a
      gradient-response association between the 3 categories of LVEF (low, low normal,
      and normal) and incident CHF but not for all-cause death.

PMID- 27038641
TI  - Biomarkers as Predictors of Cardiac Toxicity From Targeted Cancer Therapies.
AB  - BACKGROUND: Cardiac biomarkers have been extensively investigated as early
      detectors of cardiac toxicity from cancer therapies. Whereas the role of
      biomarkers in monitoring anthracycline toxicity is generally well understood,
      substantial uncertainty remains regarding their role in monitoring newer targeted
      cancer therapies. METHODS AND RESULTS: This review article examines all major
      published studies using cardiac troponins and/or N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) in monitoring for cardiac toxicity with
      trastuzumab, tyrosine kinase inhibitors, and mammalian target of rapamycin (mTOR)
      inhibitors. There is substantial variability among studies regarding biomarker
      assays used, sensitivity of the assays, and definitions of abnormal results. In
      general, troponin I predicts early but not late cardiac events when trastuzumab
      is administered after anthracyclines, but troponin increases likely reflect
      anthracycline injury rather than trastuzumab injury. NT-proBNP detects cardiac
      toxicity with tyrosine kinase inhibitors and mTOR inhibitors, but not
      independently from echocardiography. CONCLUSIONS: Troponin I can serve as a
      marker for susceptibility to cardiac toxicity during early trastuzumab treatment
      in patients who have received recent anthracyclines. NT-proBNP can serve as a
      useful marker of cardiac toxicity in patients treated with tyrosine kinase
      inhibitors or mTOR inhibitors if echocardiographic screening is not being used.

PMID- 27038642
TI  - Cardio-Oncology Training: A Proposal From the International Cardioncology Society
      and Canadian Cardiac Oncology Network for a New Multidisciplinary Specialty.
AB  - There is an increasing awareness and clinical interest in cardiac safety during
      cancer therapy as well as in optimally addressing cardiac issues in cancer
      survivors. Although there is an emerging expertise in this area, known as cardio
      oncology, there is a lack of organization in the essential components of
      contemporary training. This proposal, an international consensus statement
      organized by the International Cardioncology Society and the Canadian Cardiac
      Oncology Network, attempts to marshal the important ongoing efforts for training
      the next generation of cardio-oncologists. The necessary elements are outlined,
      including the expectations for exposure necessary to develop adequate training.
      There should also be a commitment to local, regional, and international education
      and research in cardio-oncology as a requirement for advancement in the field. 

PMID- 27038643
TI  - Biological approach for the management of non-healing diabetic foot ulcers.
AB  - OBJECTIVE: To show an approach to profit of the main components of platelet rich
      plasma (PRP), i.e. the signaling proteins, and the fibrin scaffold and discuss
      the intervention within TIME (Tissue, Inflammation/Infection, Moisture, Edges)
      framework. METHODS: Two patients with diabetic foot ulcers are treated with both
      liquid and gelled PRP, and the rationale for the PRP intervention is described
      herein. Autologous blood is withdrawn and, PRP is separated by single spinning
      and activated with CaCl2 prior to application. PRP is injected in an activated
      liquid form, i.e. freshly activated, before coagulation, within the wound edges.
      In fibrotic tissue PRP is introduced performing a needling procedure. In
      addition, PRP, clotted ex-vivo, is applied in the wound bed as a primary
      dressing. RESULTS: Both patients responded positively to PRP intervention. Case 1
      healed after five weekly PRP applications. Case 2 healed after eight weekly PRP
      applications. Patient satisfaction was high in both cases. The procedure had no
      complications, is well tolerated and easy to perform in any medical setting.
      CONCLUSION: PRP intervention is safe and if associated with correct tissue
      debridement and preparation of the host tissue it may help to decrease the burden
      of diabetic foot ulcers. Carefully designed randomized clinical trials with
      special attention to the PRP procedure are needed to assess the efficacy of these
      interventions.

PMID- 27038644
TI  - Invasive Lobular Cancer of the Breast: A Pictorial Essay of Imaging Findings on
      Mammography, Sonography, and Magnetic Resonance Imaging.

PMID- 27038645
TI  - PNPLA3 gene in liver diseases.
AB  - Genome-wide association studies (GWAS) in the field of liver diseases have
      revealed previously unknown pathogenic loci and generated new biological
      hypotheses. In 2008, a GWAS performed in a population-based sample study, where
      hepatic liver fat content was measured by magnetic spectroscopy, showed a strong
      association between a variant (rs738409 C>G p.I148M) in the patatin-like
      phospholipase domain containing 3 (PNPLA3) gene and nonalcoholic fatty liver
      disease. Further replication studies have shown robust associations between
      PNPLA3 and steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma on a
      background of metabolic, alcoholic, and viral insults. The PNPLA3 protein has
      lipase activity towards triglycerides in hepatocytes and retinyl esters in
      hepatic stellate cells. The I148M substitution leads to a loss of function
      promoting triglyceride accumulation in hepatocytes. Although PNPLA3 function has
      been extensively studied, the molecular mechanisms leading to hepatic fibrosis
      and carcinogenesis remain unclear. This unsuspected association has highlighted
      the fact that liver fat metabolism may have a major impact on the pathophysiology
      of liver diseases. Conversely, alone, this locus may have limited predictive
      value with regard to liver disease outcomes in clinical practice. Additional
      studies at the genome-wide level will be required to identify new variants
      associated with liver damage and cancer to explain a greater proportion of the
      heritability of these phenotypes. Thus, incorporating PNPLA3 and other genetic
      variants in combination with clinical data will allow for the development of
      tailored predictive models. This attractive approach should be evaluated in
      prospective cohorts.

PMID- 27038646
TI  - Cancer prevention and therapy through the modulation of transcription factors by
      bioactive natural compounds.
AB  - The association between chronic inflammation and cancer development has been well
      documented. One of the major obstacles in cancer treatment is the persistent
      autocrine and paracrine activation of pro-inflammatory transcription factors such
      as nuclear factor-kappaB, signal transducer and activator of transcription 3,
      activator protein 1, fork head box protein M1, and hypoxia-inducible factor
      1alpha in a wide variety of tumor cell lines and patient specimens. This, in
      turn, leads to an accelerated production of cellular adhesion molecules,
      inflammatory cytokines, chemokines, anti-apoptotic molecules, and inducible
      nitric oxide synthase. Numerous medicinal plant-derived compounds have made a
      tremendous impact in drug discovery research endeavors, and have been reported to
      modulate the activation of diverse oncogenic transcription factors in various
      tumor models. Moreover, novel therapeutic combinations of standard
      chemotherapeutic drugs with these agents have significantly improved patient
      survival by making cancer cells more susceptible to chemotherapy and
      radiotherapy. In this review, we critically analyze the existing literature on
      the modulation of diverse transcription factors by various natural compounds and
      provide views on new directions for accelerating the discovery of novel drug
      candidates derived from Mother Nature.

PMID- 27038647
TI  - Towards personalized diagnostics via longitudinal study of the human plasma N
      glycome.
AB  - Facilitated by substantial advances in analytical methods, plasma N-glycans have
      emerged as potential candidates for biomarkers. In the recent years, several
      investigations could link aberrant plasma N-glycosylation to numerous diseases.
      However, due to often limited specificity and sensitivity, only a very limited
      number of glycan biomarkers were approved by the authorities up to now. The inter
      individual heterogeneity of the plasma N-glycomes might mask disease related
      changes in conventional large cross-sectional cohort studies, with a one-time
      sampling approach. But, a possible benefit of longitudinal sampling in biomarker
      discovery could be, that already small changes during disease progression are
      revealed, by monitoring the plasma N-glycome of individuals over time. To
      evaluate this, we collected blood plasma samples of five healthy donors over a
      time period of up to six years (min. 1.5 years). The plasma N-glycome was
      analyzed by xCGE-LIF, to investigate the intra-individual N-glycome variability
      over time. It is shown, that the plasma N-glycome of an individual is remarkably
      stable over a period of several years, and that observed small longitudinal
      changes are independent from seasons, but significantly correlated with lifestyle
      and environmental factors. Thus, the potential of future longitudinal biomarker
      discovery studies could be demonstrated, which is a further step towards
      personalized diagnostics. This article is part of a Special Issue entitled
      "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

PMID- 27038648
TI  - An experimental model of affinity filtration for the isolation of egg white
      Lysozyme using Cibacron Blue immobilized to yeast cells.
AB  - An experimental model of affinity filtration process was designed using a
      macroligand composed by Cibacron Blue F3GA immobilized to yeast cells. Its
      performance was evaluated, at bench scale, through the recovery of egg white
      Lysozyme. The selective and reversible binding between the Cibacron ligand
      molecule and the enzyme is described. The separation of Lysozyme from the protein
      mixture included the application of stages such as affinity adsorption,
      concentration, diafiltration and elution. A tangential microfiltration system
      with an inorganic membrane was designed. The main finding was the development of
      the diafiltration operation, key stage in the enzyme isolation. The macroligand
      particle kept its integrity along the whole process and the degree of purity of
      the isolated Lysozyme was significant. 

PMID- 27038649
TI  - A comparative study of various physicochemically modified capillaries used in CE
      technique for the three distinct analytical purposes.
AB  - The five different commercially offered capillaries, bare silica, one dynamically
      and three permanently coated, have been tested with respect to the three distinct
      bioanalytical issues: (i) achiral and chiral separation of small mass molecules,
      warfarin and its six isomeric hydroxy-derivatives; (ii) ultraselective separation
      of transferrin and albumin including differentiation between the diferric, two
      monoferric and iron-free forms of transferrin; and (iii) pioneering
      identification of albumin-induced shifts of acid dissociation constant by using
      CE instrumentation, revealed for warfarin and six hydroxywarfarins. As a result
      all of these pharmacologically and biochemically-relevant purposes have been
      reached, but using different capillaries. The dynamically coated silica capillary
      has allowed for the first time to separate warfarin from its six main hydroxy
      metabolites by CE with high resolution. The bare silica capillary has performed
      well in cyclodextrin-assisted enantioseparation of these compounds. The neutral
      capillary has provided excellent resolution and performance in separation of
      proteins. The amine capillary, in turn, has occurred to be the best choice for
      identification of albumin-induced pKa shifts occurring in vivo, omitting
      capillary clogging and providing better sensitivity than the neutral capillary.
      This work reveals specific predispositions and shows that there is no universal
      capillary which may be applied to all issues. 

PMID- 27038650
TI  - A validated ultra-performance liquid chromatography-tandem mass spectrometry
      method to identify the pharmacokinetics of SR8278 in normal and streptozotocin
      induced diabetic rats.
AB  - There is a relationship between circadian rhythm and metabolic disorders. The
      active agent, SR8278, could competitively bind to and inhibit the nuclear
      receptor, Rev-erb (a major modulator of mammalian circadian clock system), to
      regulate the metabolism in organisms. However, we had limited knowledge of the
      pharmacokinetic (PK) characteristics of SR8278. Here, we describe a sensitive and
      reproducible ultra-performance liquid chromatography-tandem mass spectrometric
      (UPLC-MS/MS) method to quantify SR8278 in vivo. The linearity range and the limit
      of quantification (LOQ) for SR8278 were 30-3000 ng/mL and 6 ng/mL, respectively.
      The inter-day and intra-day variability were within 10%. This UPLC-MS/MS method
      was successfully used to characterize the PK behaviors of SR8278 in normal and
      diabetic rats after intravenous (i.v.) injection at a dosage of 2mg/kg. No
      significant differences were observed in the PK parameters of SR8278 in normal
      and diabetic rats. Specifically, the values of areas under plasma concentration
      time curves (AUC), initial plasma concentrations (C0), elimination half-lives
      (t1/2), and clearances (CL) were 608.33 +/- 295.25 vs. 598.59 +/- 276.92 ng.h/mL,
      2410.25 +/- 202.36 vs. 3742.11 +/- 1300.21 ng/mL, 0.17 +/- 0.08 vs. 0.11 +/- 0.04
      h, 3330.83 +/- 1609.48 vs. 3364.81 +/- 1111.38 mL/kg.h for SR8278 in normal rats
      vs. diabetic rats, respectively. In conclusion, a UPLC-MS/MS method was
      successfully developed and validated for the first time, with a wide linearity
      range, low LOQ, small sample volume (10 MUL), rapid analysis (4 min) and
      excellent recoveries (>80%). It was also used to clarify the PK characteristics
      of SR8378 in rats. The same PK behaviors of SR8278 in normal and diabetic rats
      showed that diabetes may have little or no effect on the disposition, metabolism
      and/or elimination in vivo, which may be of great importance for future clinical
      studies.

PMID- 27038651
TI  - SpeB proteolysis with imaged capillary isoelectric focusing for the
      characterization of domain-specific charge heterogeneities of reference and
      biosimilar Rituximab.
AB  - The charge variations of therapeutic monoclonal antibody reveal important
      information of the post-translational modifications that may potentially impact
      the potency and safety of pharmaceutical products, especially during the
      evaluation of biosimilarity of therapeutic proteins. In this work, a novel SpeB
      based proteolysis strategy coupling with imaged capillary isoelectric focusing
      was developed for the determination of domain-specific charge heterogeneities of
      innovator and generic Rituximab drug products from United States, European and
      Indian markets. It was observed that innovator Rituximab from the United States
      and Europe share highly similar peak distributions and charge heterogeneities
      with 26.2-26.6% Fc/2, 28.9-29.3% LC and 44.4-44.5% Fd peak areas detected,
      respectively, while multiple basic variations of Fc/2 and less acidic LC and Fd
      species were found from generic Rituximab from India with 20.9% Fc/2, 32.3% LC
      and 46.9% Fd peak areas detected. It was also demonstrated that structural
      changes caused by Carboxypeptidase B treatment and deamidation study at pH
      extremes could be sensitively captured with the established method, with the
      results further indicating that the generic product's basic variations of Fc/2
      were un-cleaved Lysine residues, while the lack of certain acidic peaks on LC and
      Fd probably was due to the lower level of deamidation. This new strategy could
      become a useful tool to reveal domain-specific charge heterogeneities profiles of
      a variety of therapeutic monoclonal antibodies in regulated environments. 

PMID- 27038652
TI  - Lymphomatous involvement of the central nervous system.
AB  - Lymphoma may arise within the central nervous system (CNS), known as primary CNS
      lymphoma (PCNSL) or may involve the CNS secondary to systemic disease. Clinical
      features are non-specific. A provisional diagnosis of PCNSL can be made on
      imaging, potentially changing the management algorithm from neurosurgical
      resection to biopsy. PCNSL in immunocompetent patients generally presents late,
      is solid, is bright on diffusion weighted imaging and shows uniform enhancement.
      Contiguity with a cerebrospinal fluid (CSF) surface and perivascular enhancement
      are useful clues. Immunocompromised patients, on the other hand, present earlier
      and often have multiple, necrotic, haemorrhagic lesions with irregular or rim
      enhancement. Secondary CNS involvement predominantly affects the leptomeninges.
      This review illustrates the varied imaging features of CNS lymphoma, atypical
      presentations, and differential diagnoses. 

PMID- 27038653
TI  - Impact of a short walking exercise on gait kinematics in children with cerebral
      palsy who walk in a crouch gait.
AB  - BACKGROUND: Crouch gait results in an increase of the joint stress due to an
      excessive knee flexion. Daily walking exercises, even when performed at a self
      selected speed, may result in a decrease of the extensor muscle strength which
      could lead to a more severe crouch gait pattern. The aim of this study was to
      assess the impact of a short walking exercise on gait kinematics in children with
      cerebral palsy who walk with a crouch gait. METHODS: Seven children with cerebral
      palsy who walk with a crouch gait were asked to walk for 6min at a self-selected
      speed. The spatio-temporal and kinematic measures, as well as the center of mass
      position were compared before and after the exercise. FINDINGS: There was no
      significant difference between walking speed before and after the walking
      exercise. Knee flexion and the maximal ankle dorsiflexion increased after the
      walking exercise. The vertical position of the center of mass decreased. No
      significant difference was found at the hip. INTERPRETATION: Children with
      cerebral palsy who walk with a crouch gait were more crouched after a 6-min
      walking exercise performed at their self-selected speed. These gait modifications
      could be due to fatigue of the extensor muscle groups. This study highlighted
      that a short walking exercise, corresponding to daily mobility, results in gait
      pattern modifications. Since therapies in children with cerebral palsy aim to
      improve motor function in everyday life situations, it could be relevant to
      evaluate gait adaptation after a few minutes of walking exercise.

PMID- 27038654
TI  - MicroRNA-107 prevents amyloid-beta induced blood-brain barrier disruption and
      endothelial cell dysfunction by targeting Endophilin-1.
AB  - The disruption of blood-brain barrier (BBB) and endothelial cell dysfunction,
      associated with the cerebrovascular deposition of the amyloid-beta (Abeta)
      protein, have been characterized as the key pathological characteristics in
      Alzheimer's disease (AD). In various biologic processes of AD, researchers have
      proven that mircroRNAs (miRNAs) play critical roles. However, the role and
      function of miRNAs in the disruption of BBB of AD still remain unclear. Here, we
      found that mircroRNA-107 (miR-107) is endogenously expressed in human brain
      microvascular endothelial cells (ECs) of BBB model, while it is significantly
      down-regulated in ECs pre-incubated with Abeta. Abeta significantly impairs the
      integrity, increases the permeability of BBB, inhibits the viability of
      endothelial cells (ECs), and meanwhile down-regulates the expression of tight
      junction proteins ZO-1, Occludin and Claudin-5. Overexpression of miR-107 largely
      abrogated Abeta-induced disruption of BBB and endothelial cell dysfunction.
      Furthermore, overexpression of miR-107 also down-regulates endophilin-1, which is
      involved in the regulation of BBB permeability and the expression of ZO-1,
      Occludin, and Claudin-5. Both bioinformatics and luciferase reporter assays
      demonstrated that Endophilin-1 was a direct and functional downstream target of
      miR-107. In conclusion, our results indicate that overexpression of miR-107 is
      able to prevent Abeta-induced blood-brain barrier disruption and endothelial cell
      dysfunction by targeting endophilin-1.

PMID- 27038655
TI  - Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9
      activation by Hexachlorobenzene in human endometrial stromal cells.
AB  - Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic
      reproductive effects in laboratory animals. It is a dioxin-like compound and a
      weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is
      characterized by the presence of functional endometrial tissues outside the
      uterine cavity. Experimental studies indicate that exposure to organochlorines
      can interfere with both hormonal regulation and immune function to promote
      endometriosis. Altered expression of metalloproteinases (MMPs) in patients with
      endometriosis, suggests that MMPs may play a critical role. In the endometriotic
      lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to
      its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting
      endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and
      expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced
      effects. We have used different in vitro models: (1) human endometrial stromal
      cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3)
      primary cultures of endometrial stromal cells from eutopic endometrium of control
      (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances
      MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were
      elevated in all models, while the MMP-2 expression only increased in ESC cells.
      HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase
      activation in T-HESC. Besides, we observed that AhR is implicated in these HCB
      induced effects. In conclusion, our results show that HCB exposure could
      contribute to endometriosis development, affecting inflammation and invasion
      parameters of human endometrial cells.

PMID- 27038656
TI  - Brain alpha7 nicotinic acetylcholine receptors in MPTP-lesioned monkeys and
      parkinsonian patients.
AB  - L-DOPA-induced dyskinesias (LID) appear in the majority of Parkinson's disease
      (PD) patients. Nicotinic acetylcholine (nACh) receptor-mediated signaling has
      been implicated in PD and LID and modulation of brain alpha7 nACh receptors might
      be a potential therapeutic target for PD. This study used [(125)I]alpha
      Bungarotoxin autoradiography to investigate alpha7 nACh receptors in LID in post
      mortem brains from PD patients (n=14) and control subjects (n=11), and from 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with
      saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP)
      (n=5), and control monkeys (n=4). MPEP is the prototypal metabotropic glutamate 5
      (mGlu5) receptor antagonist; it reduced the development of LID in these monkeys.
      [(125)I]alpha-Bungarotoxin specific binding to striatal and pallidal alpha7 nACh
      receptors were only increased in L-DOPA-treated dyskinetic MPTP monkeys as
      compared to controls, saline and L-DOPA+MPEP MPTP monkeys; dyskinesia scores
      correlated positively with this binding. The total group of Parkinsonian patients
      had higher [(125)I]alpha-Bungarotoxin specific binding compared to controls in
      the caudate nucleus but not in the putamen. PD patients without motor
      complications had higher [(125)I]alpha-Bungarotoxin specific binding compared to
      controls only in the caudate nucleus. PD patients with LID only had higher
      [(125)I]alpha-Bungarotoxin specific binding compared to controls in the caudate
      nucleus and compared to those without motor complications and controls in the
      putamen. PD patients with wearing-off only, had [(125)I]alpha-Bungarotoxin
      specific binding at control values in the caudate nucleus and lower in the
      putamen. Reduced motor complications were associated with normal striatal alpha7
      nACh receptors, suggesting the potential of this receptor to manage motor
      complications in PD.

PMID- 27038657
TI  - Soluble Immune Response Suppressor (SIRS): Reassessing the immunosuppressant
      potential of an elusive peptide.
AB  - A previously studied immunosuppressive cytokine, Soluble Immune Response
      Suppressor (SIRS), may have relevance to current studies of immune suppression in
      a variety of human disease states. Despite extensive efforts using experimental
      models, mainly in mice, much remains to be discovered as to how autoimmune cells
      in mice and humans escape normal regulation and, conversely, how tumor cells
      evade evoking an immune response. It is the contention of this commentary that
      the literature pre-2000 contain results that might inform current studies. The
      broadly immunosuppressive protein, SIRS, was studied extensively from the 1970s
      to 1990s and culminated in the determination of the n-terminal 21mer sequence of
      this 15kDa protein which had high homology to the short neurotoxins from sea
      snakes, that are canonical members of the three finger neurotoxin superfamily
      (3FTx). It was not until 2007 that the prophylactic administration of the
      synthetic N-terminal peptide of the SIRS 21mer, identical to the published
      sequence, was reported to inhibit or delay the development of two autoimmune
      diseases in mice: experimental allergic encephalomyelitis (EAE) and type I
      diabetes (T1D). These findings were consistent with other studies of the 3FTx
      superfamily as important probes in the study of mammalian pharmacology. It is the
      perspective of this commentary that SIRS, SIRS peptide and the anti-peptide mAb,
      represent useful, pharmacologically-active probes for the study of the immune
      response as well as in the potential treatment of autoimmune, inflammatory
      diseases and cancer.

PMID- 27038658
TI  - A rapid screening method using DNA binding dyes to determine whether hair
      follicles have sufficient DNA for successful profiling.
AB  - We report a simple screening method to assess the viability of successful DNA
      profiling from single hair follicles. A total of 48 hair samples (shed and
      plucked) were collected from male and female donors and the root tips (0.5cm)
      were stained using one of three DNA binding dyes (EvaGreenTM, DiamondTM Nucleic
      Acid Dye and RedSafeTM) at 20* concentration. The hairs were subsequently viewed
      under a Nikon Optiphot fluorescent microscope to count the approximate number of
      nuclei in one plane of view. The hairs were then processed using either (1) a DNA
      extraction kit (QIAmp((r)) Mini Kit) and then amplified using the AmpFLSTR((r))
      NGMTM kit, which amplifies 15 short tandem repeat (STR) loci plus the gender
      marker amelogenin, or (2) by direct PCR amplification using the same DNA
      profiling kit. DiamondTM dye had the lowest background signal and plucked hairs
      treated with this dye produced full DNA profiles when amplified directly and was
      chosen to screen a further 150 mixed hair samples. These hairs were separated
      into one of five categories (1, >100 nuclei; 1.5, 50-99 nuclei; 2, 1-49 nuclei;
      2.5, no nuclei but high fluorescent signal; 3, no nuclei and very low fluorescent
      signal) from which 60 of the hairs were chosen to undergo direct amplification
      using the NGMTM kit. It was found that there was a direct correlation to the
      category designation and the ability to obtain a DNA profile up-loadable to the
      Australian DNA Database. Approximately 91% of category 1 hairs resulted in either
      a full or high partial (12-29 alleles) profile by direct PCR whereas about 78% of
      category 3 hairs exhibited no amplification. The results show that this method
      can be used to predict successful STR amplification from single hair follicles.
      It is a rapid, sensitive, cheap, non-destructive and easy to perform methodology
      applicable for screening multiple hairs in order to aid forensic investigators in
      predicting hairs that will yield DNA results. 

PMID- 27038659
TI  - Gabapentin concentrations and postmortem distribution.
AB  - Gabapentin is a widely prescribed medication used primarily for the treatment of
      epilepsy and neuropathic pain. Gabapentin has a favorable adverse effect profile
      in therapeutic dosing with the most common reported effects being dizziness,
      fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional
      self-poisonings, serious effects are generally rare. In this report, gabapentin
      analyses were performed on 30 postmortem cases that had peripheral blood, central
      blood and liver tissue. Overall the central to peripheral blood (C/P) ratio mean
      was 0.90+/-0.24 (mean+/-standard deviation), and a median of 0.97. The liver to
      peripheral blood (L/P) ratio mean was 0.68+/-0.26L/kg (mean+/-standard
      deviation), and a median of 0.65L/kg. An additional case, where both antemortem
      blood and postmortem peripheral blood specimens were available, revealed the same
      gabapentin concentration in both specimens. Taken together, the data presented
      suggests that gabapentin is unlikely to show postmortem redistribution. 

PMID- 27038660
TI  - Resource use in pediatric blunt and penetrating trauma.
AB  - BACKGROUND: Trauma is one of the leading causes of pediatric morbidity and
      mortality with significant patient and economic impacts that necessitate constant
      study. Significant differences in outcomes and resource use exist between blunt
      and penetrating mechanisms. METHODS: The National Trauma Data Bank was analyzed
      for patients aged 0-18 y with International Classification of Diseases, 9th
      Revision injury codes for blunt and penetrating trauma from 2007-2012.
      Demographic information, causes, treatments, complications, and outcomes were
      assessed. RESULTS: A total of 748,347 pediatric trauma patients were assessed.
      Blunt trauma was identified as the cause in 601,898 (80.43%) patients compared
      with 55,597 (7.4%) patients with penetrating trauma. Blunt trauma patients were
      younger on average and more likely to be female. Despite having a slightly higher
      mean injury severity scores, blunt trauma patients had shorter length of stay in
      the hospital (2.9 versus 4.3 d, P < 0.001), fewer complications (34.8% versus
      38.6%, P < 0.001), and a much lower mortality rate (1.3% versus 7.1%, P < 0.001).
      Blunt trauma patients were more likely to undergo computed tomography scanning
      but less likely to receive transfusions (1.79% versus 5.5%, P < 0.001) and to
      undergo exploratory laparotomy (0.9% versus 9.4%, P < 0.001) and thoracotomy
      (0.07% versus 1.7%, P < 0.001). Variations in outcome and resource use were also
      noted by age. CONCLUSIONS: Compared with penetrating trauma, blunt trauma is more
      common and patients have shorter length of stay, less complications, lower
      mortality, and are less likely to need operative intervention or blood
      transfusion. Resource use also varied by age.

PMID- 27038661
TI  - Thoracic irrigation prevents retained hemothorax: a pilot study.
AB  - BACKGROUND: Upward of 20% of patients undergoing thoracostomy tube (TT) placement
      develop retained hemothorax (HTx) requiring secondary intervention. The aim of
      this study was to define the rate of secondary intervention in patients
      undergoing prophylactic thoracic irrigation. METHODS: A prospective observational
      trial of 20 patients who underwent thoracic irrigation at the time of TT
      placement was conducted. Patients with HTx identified on chest x-ray were
      included. After standard placement of a 36-French TT, the HTx was evacuated using
      a sterile suction catheter advanced within the TT. Warmed sterile saline was
      instilled into the chest through the TT followed by suction catheter evacuation.
      The TT was connected to the sterile drainage atrium and suction applied. TTs were
      managed in accordance with our standard division protocol. RESULTS: The
      population was predominantly (70%) male at median age 35 years, median ISS 13,
      with 55% suffering penetrating trauma. Thirteen (65%) patients underwent TT
      placement within 6 h of trauma with the remainder within 24 h. Nineteen patients
      received the full 1000-mL irrigation. The majority demonstrated significant
      improvement on postprocedure chest x-ray. The secondary intervention rate was 5%.
      A single patient required VATS on post-trauma day zero for retained HTx. Median
      TT duration was 5 d with median length of stay of 7 d. No adverse events related
      to the pleural lavage were noted. CONCLUSIONS: Thoracic irrigation at the time of
      TT placement for traumatic HTx may decrease the rate of retained HTx.

PMID- 27038662
TI  - Blood loss and outcomes after resection of colorectal liver metastases.
AB  - BACKGROUND: The influence of intraoperative blood loss (IBL) on long-term
      outcomes of patients undergoing liver resection for colorectal cancer liver
      metastases (CRLM) remains not well defined. MATERIALS AND METHODS: A total of 433
      patients who underwent curative-intent hepatic resection for CRLM between 2000
      and 2013 at Johns Hopkins were identified. Demographics, IBL data, and long-term
      outcomes were collected and analyzed. Clinicopathologic predictors of IBL and the
      association of IBL and outcomes were assessed. RESULTS: The median patient age
      was 54 y (interquartile range, 44-64), most patients were male (58.9%; n = 255).
      At surgery, the median IBL was 400 mL (range, 10-5100 mL). Two-hundred eighty
      seven patients (66.3%) had an IBL of >250 mL. Factors associated with increased
      IBL (>250 mL) on multivariate analysis were male sex (odds ratio [OR], 2.62; 95%
      confidence interval [CI], 1.68-4.09; P < 0.001), tumor size >3 cm (OR, 1.88; 95%
      CI, 1.18-2.99; P = 0.008), and major hepatic resection (OR, 3.08; 95% CI, 1.92
      4.92; P < 0.001). At a median follow-up time of 30.6 mo, the median survival
      times were 70.5, 56.4, and 36.9 mo for IBL <250, 250-1000, and >1000 mL,
      respectively (P = 0.004). IBL >250 mL remained an independent prognostic factor
      of overall survival in multivariate analysis (hazard ratio, 1.41; 95% CI, 1.01
      1.97; P = 0.04) after adjusting for other factors including the receipt of blood
      transfusion. CONCLUSIONS: The magnitude of IBL during CRLM resection was related
      to biologic characteristics of the tumor and the extent of surgery. Increased IBL
      during CRLM resection was an independent prognostic factor for worse patient
      survival. Furthermore, a dose-response relationship between increasing IBL and
      worsening survival was evident.

PMID- 27038663
TI  - Multi-scale segmentation of neurons based on one-class classification.
AB  - BACKGROUND: High resolution multiphoton and confocal microscopy has allowed the
      acquisition of large amounts of data to be analyzed by neuroscientists. However,
      manual processing of these images has become infeasible. Thus, there is a need to
      create automatic methods for the morphological reconstruction of 3D neuronal
      image stacks. NEW METHOD: An algorithm to extract the 3D morphology from a neuron
      is presented. The main contribution of the paper is the segmentation of the
      neuron from the background. Our segmentation method is based on one-class
      classification where the 3D image stack is analyzed at different scales. First, a
      multi-scale approach is proposed to compute the Laplacian of the 3D image stack.
      The Laplacian is used to select a training set consisting of background points. A
      decision function is learned for each scale from the training set that allows
      determining how similar an unlabeled point is to the points in the background
      class. Foreground points (dendrites and axons) are assigned as those points that
      are rejected as background. Finally, the morphological reconstruction of the
      neuron is extracted by applying a state-of-the-art centerline tracing algorithm
      on the segmentation. RESULTS: Quantitative and qualitative results on several
      datasets demonstrate the ability of our algorithm to accurately and robustly
      segment and trace neurons. COMPARISON WITH EXISTING METHOD(S): Our method was
      compared to state-of-the-art neuron tracing algorithms. CONCLUSIONS: Our approach
      allows segmentation of thin and low contrast dendrites that are usually difficult
      to segment. Compared to our previous approach, this algorithm is more accurate
      and much faster.

PMID- 27038664
TI  - Ketone Bodies Signal Opportunistic Food-Seeking Activity.
AB  - Food-seeking activity at a predictable time of the day is one of the fundamental
      'opportunistic behaviors' for survival. The neural and molecular basis for such
      anticipatory activity is not clearly understood. However, a new report shows
      that, after several hours of fasting, liver-derived ketone bodies have a key role
      in this behavior.

PMID- 27038665
TI  - Simulating evolution of protein complexes through gene duplication and co-option.
AB  - We present a model of the evolution of protein complexes with novel functions
      through gene duplication, mutation, and co-option. Under a wide variety of input
      parameters, digital organisms evolve complexes of 2-5 bound proteins which have
      novel functions but whose component proteins are not independently functional.
      Evolution of complexes with novel functions happens more quickly as gene
      duplication rates increase, point mutation rates increase, protein complex
      functional probability increases, protein complex functional strength increases,
      and protein family size decreases. Evolution of complexity is inhibited when the
      metabolic costs of making proteins exceeds the fitness gain of having functional
      proteins, or when point mutation rates get so large the functional proteins
      undergo deleterious mutations faster than new functional complexes can evolve.

PMID- 27038667
TI  - The sex ratio of the sibs of probands diagnosed with autism.

PMID- 27038666
TI  - A generative modeling approach to connectivity-Electrical conduction in vascular
      networks.
AB  - The physiology of biological structures is inherently dynamic and emerges from
      the interaction and assembly of large collections of small entities. The extent
      of coupled entities complicates modeling and increases computational load. Here,
      microvascular networks are used to present a novel generative approach to
      connectivity based on the observation that biological organization is
      hierarchical and composed of a limited set of building blocks, i.e. a vascular
      network consists of blood vessels which in turn are composed by one or more cell
      types. Fast electrical communication is crucial to synchronize vessel tone across
      the vast distances within a network. We hypothesize that electrical conduction
      capacity is delimited by the size of vascular structures and connectivity of the
      network. Generation and simulation of series of dynamical models of electrical
      spread within vascular networks of different size and composition showed that (1)
      Conduction is enhanced in models harboring long and thin endothelial cells that
      couple preferentially along the longitudinal axis. (2) Conduction across a branch
      point depends on endothelial connectivity between branches. (3) Low connectivity
      sub-networks are more sensitive to electrical perturbations. In summary, the
      capacity for electrical signaling in microvascular networks is strongly shaped by
      the morphology and connectivity of vascular (particularly endothelial) cells.
      While the presented software can be used by itself or as a starting point for
      more sophisticated models of vascular dynamics, the generative approach can be
      applied to other biological systems, e.g. nervous tissue, the lymphatics, or the
      biliary system.

PMID- 27038668
TI  - The influence of dispersal on a predator-prey system with two habitats.
AB  - Dispersal between different habitats influences the dynamics and stability of
      populations considerably. Furthermore, these effects depend on the local
      interactions of a population with other species. Here, we perform a general and
      comprehensive study of the simplest possible system that includes dispersal and
      local interactions, namely a 2-patch 2-species system. We evaluate the impact of
      dispersal on stability and on the occurrence of bifurcations, including pattern
      forming bifurcations that lead to spatial heterogeneity, in 19 different classes
      of models with the help of the generalized modelling approach. We find that
      dispersal often destabilizes equilibria, but it can stabilize them if it
      increases population losses. If dispersal is nonrandom, i.e. if emigration or
      immigration rates depend on population densities, the correlation of stability
      with dispersal rates is positive in part of the models. We also find that many
      systems show all four types of bifurcations and that antisynchronous oscillations
      occur mostly with nonrandom dispersal.

PMID- 27038669
TI  - Discrete-time moment closure models for epidemic spreading in populations of
      interacting individuals.
AB  - Understanding the dynamics of spread of infectious diseases between individuals
      is essential for forecasting the evolution of an epidemic outbreak or for
      defining intervention policies. The problem is addressed by many approaches
      including stochastic and deterministic models formulated at diverse scales
      (individuals, populations) and different levels of detail. Here we consider
      discrete-time SIR (susceptible-infectious-removed) dynamics propagated on contact
      networks. We derive a novel set of 'discrete-time moment equations' for the
      probability of the system states at the level of individual nodes and pairs of
      nodes. These equations form a set which we close by introducing appropriate
      approximations of the joint probabilities appearing in them. For the example case
      of SIR processes, we formulate two types of model, one assuming statistical
      independence at the level of individuals and one at the level of pairs. From the
      pair-based model we then derive a model at the level of the population which
      captures the behavior of epidemics on homogeneous random networks. With respect
      to their continuous-time counterparts, the models include a larger number of
      possible transitions from one state to another and joint probabilities with a
      larger number of individuals. The approach is validated through numerical
      simulation over different network topologies.

PMID- 27038670
TI  - AmyI-1-18, a cationic alpha-helical antimicrobial octadecapeptide derived from
      alpha-amylase in rice, inhibits the translation and folding processes in a
      protein synthesis system.
AB  - In our previous study, we used a cell-free rapid translation system (RTS), which
      is an in vitro protein synthesis system based on Escherichia coli lysate, for
      evaluating the inhibition of green fluorescent protein (GFP) synthesis by
      pyrrhocoricin. In this study, using an RTS, we evaluated the inhibition of GFP
      synthesis by AmyI-1-18, an antimicrobial octadecapeptide. We found that,
      similarly to pyrrhocoricin, AmyI-1-18 inhibited GFP synthesis in the RTS in a
      concentration-dependent manner. In addition, the blockage of transcription and
      translation steps in the RTS was individually estimated using RT-PCR after gene
      expression to determine the mRNA products and using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis to determine the amounts of GFP expressed from
      purified mRNA, respectively. The results demonstrated that the inhibition of GFP
      synthesis by AmyI-1-18 did not occur at the transcription step but rather at the
      translation step. Furthermore, we assessed the inhibition of DnaK-mediated
      refolding of chemically denatured luciferase by AmyI-1-18; AmyI-1-18 inhibited
      the protein folding activity of the ATP-dependent DnaK/DnaJ molecular chaperone
      system in a concentration-dependent manner. Surface plasmon resonance (SPR)
      analysis showed that AmyI-1-18 strongly bound to RNA with a KD value of 1.4 * 10(
      8) M but not to DNA and that AmyI-1-18 specifically bound to DnaK with a KD value
      of 4.4 * 10(-6) M. These SPR analysis results supported the results obtained in
      both the RTS and the molecular chaperone system. These results demonstrated that
      both RNA and DnaK are most likely the target of AmyI-1-18 in the protein
      synthesis system. 

PMID- 27038671
TI  - Kinetics of bisphenol A degradation by Sphingomonas paucimobilis FJ-4.
AB  - A chemostat was operated to characterize degradation of bisphenol A by
      Sphingomonas paucimobilis FJ-4. The chemostat at 30 degrees C was fed with a
      medium containing 150 mg L(-1) of BPA as the sole carbon and energy source. At
      the short cell retention time of 8 h, the bacterial cells were washed out from
      the chemostat. At long cell retention times of 12, 16, 24, and 48 h, steady
      states of the bacterial growth on BPA degradation were achieved after a lag time
      of 16-57 h. A mathematical model was applied to evaluate the BPA degradation
      ability of strain FJ-4. The maximum specific degradation rate, the half
      saturation constant, the cell yield, and the specific decay rate were estimated
      respectively as 0.46 mg-BPA (mg-VSS h)(-1), 13.1 mg L(-1), 0.39 mg-VSS mg-BPA(
      1), and 0.0014 h(-1). 

PMID- 27038672
TI  - Screening, expression, and characterization of an anti-human oxidized low-density
      lipoprotein single-chain variable fragment.
AB  - Increased levels of oxidized low-density lipoprotein (OxLDL) in the blood
      circulation are correlated with atherosclerosis. Monoclonal antibody-based
      detection systems have been reported for OxLDL. We identified novel single-chain
      variable fragments (scFvs) having affinity for human OxLDL and related ligands.
      We constructed an scFv library from nonimmunized human spleen mRNA. Two types
      (gamma+kappa and MU+lambda) of scFv phage libraries were enriched by biopanning,
      and five scFv clones with affinity for OxLDL were identified. The gammakappa5
      scFv, which showed the highest affinity for OxLDL, was cloned into pET-22b(+) and
      expressed in Escherichia coli BL21(DE3). gammakappa5, expressed as an inclusion
      body in BL21(DE3), was refolded and purified. The specificity and sensitivity of
      gammakappa5 were analyzed using enzyme-linked immunosorbent assays (ELISAs). The
      gammakappa5 scFv showed affinity for OxLDL and acetylated LDL. The sensitivity of
      gammakappa5 to low concentrations (1-2 MUg/mL) of OxLDL was higher than that to
      AcLDL and LDL. Finally, we developed a sandwich ELISA using gammakappa5 and
      CTLD14 (a lectin-like OxLDL receptor-1 ligand recognition region), which allowed
      specific detection of OxLDL at a level below 0.1 MUg/mL. Our results indicated
      that the gammakappa5 scFv was a promising molecule for the detection of modified
      LDL at very low concentrations. 

PMID- 27038673
TI  - Sequential therapy with "vacuum sealing drainage-artificial dermis implantation
      thin partial thickness skin grafting" for deep and infected wound surfaces in
      children.
AB  - OBJECTIVE: To evaluate the efficacy of a "vacuum sealing drainage (VSD) -
      artificial dermis implantation (ADI) - thin partial thickness skin grafting
      (TSG)" sequential therapy for deep and infected wounds in children. MATERIALS AND
      METHODS: Fifty-three pediatric patients with deep and infected wounds were
      treated with sequential VSD-ADI-TSG therapy. The efficacy of this treatment was
      compared with that of the surgical debridement-change dressings-thin partial
      thickness skin grafting previously performed on 20 patients. Survival of tissue
      grafts, color and flexibility, subcutaneous fullness and scar formation of the
      graft site were examined and compared. RESULTS: The sequential therapy combined
      the advantages of the VSD treatment, in reducing tissue necrosis and infection on
      the wound surfaces and promoting the growth of granulation tissue, with the
      enhancement of grafting by artificial dermis. Compared with the 20 controls, skin
      grafted on the artificial dermis was more smooth and glossy, while the textures
      of the region were more elastic, and the scars were significantly lighter in
      Vancouver scale. CONCLUSION: The sequential VSD-ADI-TSG therapy is a simple and
      effective treatment for children with deep and infected wounds. LEVEL OF
      EVIDENCE: IV.

PMID- 27038674
TI  - Seemed Like Cellulitis: Intravascular Large B-Cell Lymphoma.

PMID- 27038675
TI  - Wide array of T-cell subpopulation alterations in patients with alcohol use
      disorders.
AB  - BACKGROUND: Alcohol abuse impacts innate and adaptive immunity and predisposes to
      infections. However, prevalence and correlations of cellular immune alterations
      in large case series is underreported. We aimed to analyze quantitative
      alterations of T-lymphocyte subpopulations in patients with alcohol use disorder
      (AUD). METHODS: cross-sectional study in patients admitted for detoxification
      between January 1, 2002 and December 31, 2012. Socio-demographic and alcohol use
      characteristics and blood samples for biochemistry, hematology and immune
      phenotype was obtained at admission. RESULTS: 238 patients (79.8%M) were
      eligible; age at admission was 43 years (interquartile range [IQR]: 38-51 years),
      the amount of alcohol consumption was 180 g/day (IQR: 120-200 g/day) and median
      duration of AUD was 18 years (IQR: 9-25 years). Compared to healthy individuals,
      50% of patients had significantly fewer double-negative (DN) T-lymphocytes (<34 *
      10(9)/L) and 23% had more double-positive (DP) T-cells (>52 * 10(9)/L). In
      addition, 24% of patients had high number of CD8(+) cells (>735 * 10(9)/L) and
      13% had low CD4(+) cell counts (<600 * 10(9)/L). In multivariable analysis, age,
      sex, serum albumin, and current cocaine use were predictors of T-cell
      subpopulation alterations. Women were three-times (OR=3.5, 95%CI:1.3-9.5) more
      likely to present with higher DP T-lymphocytes than men. CONCLUSIONS:
      Quantitative alterations of T-cell subpopulations are frequent in patients
      seeking treatment of AUD. Assessment of cellular immunity in this population may
      help to identify those at increased risk of immune alterations.

PMID- 27038677
TI  - Estradiol enhances retention but not organization of hippocampus-dependent memory
      in intact male mice.
AB  - Because estrogens have mostly been studied in gonadectomized females, effects of
      chronic exposure to environmental estrogens in the general population are
      underestimated. Estrogens can enhance hippocampus-dependent memory through the
      modulation of information storage. However, declarative memory, the hippocampus
      dependent memory of facts and events, demands more than abilities to retain
      information. Specifically, memory of repetitive events of everyday life such as
      "where I parked" requires abilities to organize/update memories to prevent
      proactive interference from similar memories of previous "parking events".
      Whether such organizational processes are estrogen-sensitive is unknown. We here
      studied, in intact young and aged adult mice, drinking-water (1MUM) estradiol
      effects on both retention and organizational components of hippocampus-dependent
      memory, using a radial-maze task of everyday-like memory. Demand on retention vs
      organization was manipulated by varying the time-interval separating repetitions
      of similar events. Estradiol increased performance in young and aged mice under
      minimized organizational demand, but failed to improve the age-associated memory
      impairment and diminished performance in young mice under high organizational
      demand. In fact, estradiol prolonged mnemonic retention of successive events
      without improving organization abilities, hence resulted in more proactive
      interference from irrelevant memories. c-Fos imaging of testing-induced brain
      activations showed that the deterioration of young memory was associated with
      dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our
      findings support the view that estradiol is promnesic but also reveal that such
      property can paradoxically impair memory. These findings have important outcomes
      regarding health issues relative to the impact of environmental estrogens in the
      general population.

PMID- 27038676
TI  - The effect of sex and irritable bowel syndrome on HPA axis response and
      peripheral glucocorticoid receptor expression.
AB  - BACKGROUND AND AIMS: Dysregulation of the hypothalamic-pituitary-adrenal (HPA)
      axis has been reported in irritable bowel syndrome (IBS). Enhanced HPA axis
      response has been associated with reduced glucocorticoid receptor (GR) mediated
      negative feedback inhibition. We aimed to study the effects of IBS status, sex,
      or presence of early adverse life events (EAL) on the cortisol response to
      corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), and
      on GR mRNA expression in peripheral blood mononuclear cells (PBMCs). METHODS:
      Rome III+ IBS patients and healthy controls underwent CRF (1MUg/kg ovine) and
      ACTH (250MUg) stimulation tests with serial plasma ACTH and cortisol levels
      measured (n=116). GR mRNA levels were measured using quantitative PCR (n=143).
      Area under the curve (AUC) and linear mixed effects models were used to compare
      ACTH and cortisol response measured across time between groups. RESULTS: There
      were divergent effects of IBS on the cortisol response to ACTH by sex. In men,
      IBS was associated with an increased AUC (p=0.009), but in women AUC was blunted
      in IBS (p=0.006). Men also had reduced GR mRNA expression (p=0.007). Cumulative
      exposure to EALs was associated with an increased HPA response. Lower GR mRNA was
      associated with increased pituitary HPA response and increased severity of
      overall symptoms and abdominal pain in IBS. CONCLUSION: This study highlights the
      importance of considering sex in studies of IBS and the stress response in
      general. Our findings also provide support for PBMC GR mRNA expression as a
      peripheral marker of central HPA response.

PMID- 27038678
TI  - Laboratory surveillance of Salmonella enterica from human clinical cases in
      Colombia 2005-2011.
AB  - INTRODUCTION: Salmonella is an enteropathogen acquired through contaminated food
      or water. In Colombia, Salmonella spp. is included in the national surveillance
      of Acute Diarrhoeal Diseases and typhoid fever initiated in 1997. This report
      shows the phenotype and genotype results obtained from 2005 to 2011. METHODS: A
      total of 4010 isolates of Salmonella enterica were analysed by serotyping with
      Kauffmann-White-LeMinor, antimicrobial resistance patterns, and pulse-field gel
      electrophoresis (PFGE). RESULTS: A total of 93 serovars were identified, of
      which, Typhimurium, Enteritidis, Typhi, Dublin, Panama, Derby, Braenderup,
      Saintpaul, and Uganda were prominent. The highest levels of resistance were found
      for tetracycline and nalidixic acid. Susceptibility was observed in 52.4%
      (2101/4010) of the isolates. Multi-resistance was recorded in 54.9% of
      Typhimurium isolates, with 81 different combinations. Using PFGE, 51.9%
      (2083/4010) isolates were analysed in 34 serovars, and 828 electrophoretic
      patterns were obtained. From these, 8 patterns were found in at least two Latin
      American countries. CONCLUSION: The surveillance of Salmonella spp. provides
      information on the serovar distribution, antimicrobial resistance, and clonal
      distribution in Colombia, as well as information to treat this disease and
      control the spread of antimicrobial bacterial resistance.

PMID- 27038679
TI  - Multiple beta-catenin mutations in hepatocellular lesions arising in Abernethy
      malformation.
AB  - An 18-year-old man underwent liver transplantation due to an Abernethy
      malformation associated with multiple hepatocellular nodules including one which
      was rapidly enlarging and was suspicious for malignant transformation. Analysis
      of the explanted liver showed a spectrum of multiple hepatocellular nodules
      ranging in appearance from focal nodular hyperplasia, hepatocellular adenoma and
      to a well-differentiated hepatocellular neoplasm borderline for hepatocellular
      carcinoma. Mutational analysis revealed wild-type beta-catenin expression in the
      background liver and some nodules, whilst different variants were present in
      other lesions irrespective of their morphological appearance. No telomerase
      reverse transcriptase (TERT) promoter mutation was identified. Abernethy
      malformations can lead to independent genetic events which can result in beta
      catenin mutations associated with malignant transformation of hepatocellular
      nodules. When following up such patients, one must therefore have a high index of
      suspicion, particularly if radiological surveillance reveals a change in the
      nature of hepatic lesions.

PMID- 27038680
TI  - Myoglobin casts in renal biopsies: immunohistochemistry and morphologic spectrum.
AB  - Five hundred eighty renal biopsies from a pool of 27850 archived cases were
      identified in which a myoglobin stain was performed because of atypical casts.
      Two hundred and thirty-eight (41%) of these biopsies were found to be positive
      for myoglobin casts. The morphology of the myoglobin casts ranged from light,
      almost translucent and refractile, to pink, to dark red and slightly brown
      granular casts by hematoxylin and eosin, to beaded globular casts that stained
      brightly fuchsinophilic with Masson trichrome and partially argyrophilic with
      silver methenamine. All biopsies displayed acute tubular injury associated with
      intratubular debris and thinning and vacuolization of tubular epithelium.
      Approximately 20% of myoglobin-positive biopsies showed calcium oxalate or
      phosphate deposition. Positive myoglobin staining was present in casts, proximal
      tubular epithelial cells without casts, and also dehisced epithelial cells.
      Collecting ducts and occasionally the distal tubular epithelium also stained
      positive. One case showed concurrent myeloma cast nephropathy with "fractured"
      casts and translucent myoglobin-positive casts. Herein, we describe the
      morphologic spectrum of myoglobin-positive casts. We conclude that utilization of
      myoglobin immunohistochemistry is advantageous and, when not available, knowledge
      of the morphologic spectrum is important.

PMID- 27038681
TI  - Expression of CEA, CA19-9, CA125, and EpCAM in pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei is a fatal clinical syndrome with mucinous tumor cells
      disseminated into peritoneal cavity and secreting abundant mucinous ascites. The
      serum tumor markers CEA, CA19-9, and CA125 are used to monitor pseudomyxoma
      peritonei remission, but their expression at tissue level has not been well
      characterized. Herein, we analyzed expression of these proteins and the
      adenocarcinoma marker EpCAM in 92 appendix-derived pseudomyxoma peritonei tumors
      by immunohistochemistry. All tumors were found to ubiquitously express CEA and
      EpCAM. In the majority of the tumors (94.6%), CEA showed polarized
      immunostaining, but in 5 aggressive high-grade tumors containing numerous signet
      ring cells, a nonpolarized staining was detected. We found preoperative CEA serum
      values to correlate with peritoneal cancer index. However, the serum values of
      the advanced cases with nonpolarized staining pattern were normal, and the
      patients died within 5 years after diagnosis. Thus, serum CEA measurements did
      not reflect aggressiveness of these tumors. CA19-9 showed strong immunopositivity
      in most of the tumors (91.3%), and mutated enzyme FUT3 was demonstrated from the
      cases showing negative or weak staining. CA125 was infrequently expressed by
      tumor cells (focal staining in 6.5% of the cases), but in most of the cases
      (79.3%), adjacent nonneoplastic mesothelial cells showed immunopositivity. As a
      conclusion, CEA and EpCAM are invariably expressed by pseudomyxoma peritonei
      tumor cells and could be exploited to targeted therapies against this malignancy.

PMID- 27038682
TI  - Immunohistochemical staining of transcription factor NFE2 for the discrimination
      of primary myelofibrosis from essential thrombocythemia.

PMID- 27038683
TI  - BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in
      node-negative breast carcinoma.
AB  - The objective of this study was to analyze the expression and clinical role of 13
      signaling molecules in a large cohort of breast carcinoma patients with long
      follow-up period. Breast carcinomas (n=410) were analyzed for protein expression
      of phosphorylated mitogen-activated protein kinases (p-ERK, p-JNK, p-p38) and
      phosphoinositide 3-kinase signaling pathway proteins (p-AKT, p-mTOR, p-p70S6K);
      the BAG family proteins BAG-1 and BAG-4/SODD; the antiapoptotic protein Bcl-2;
      the inhibitor of apoptosis family member Survivin; and the heat shock protein
      family members HSP27, HSP70, and HSP90. Protein expression was studied for
      association with clinicopathological parameters and survival. Significantly
      higher expression of p-AKT (P<.001), p-mTOR (P<.001), p-p70S6K (P<.001), Bcl-2
      (P<.001), BAG-4/SODD (P<.001), HSP27 (P<.001), HSP70 (P=.012), HSP90 (P<.001),
      and Survivin (P=.004) was found in infiltrating ductal and lobular carcinomas
      compared to mucinous carcinomas. Bcl-2 expression was significantly higher in
      grades 1 and 2 compared to grade 3 carcinomas (P<.001). p-AKT expression was
      higher in tumors more than 2cm (P=.027), whereas p-mTOR expression was lowest in
      tumors more than 5cm (P=.019). Higher BAG-4/SODD, HSP70, and HSP90 expression was
      associated with poor overall survival (P=.016, P=.039, and P=.023, respectively)
      in univariate analysis, whereas the only independent prognosticator in Cox
      multivariate survival analysis was tumor diameter (P=.003). In conclusion, BAG
      4/SODD, HSP70, and HSP90 are potential prognostic markers in node-negative breast
      carcinoma that merit further research.

PMID- 27038684
TI  - Giant intra-abdominal mature cystic teratoma (dermoid cyst) in an adult man, with
      male genitourinary tissue including prostatic and penile elements.
AB  - We describe a case of a giant intra-abdominal mature cystic teratoma in a 36-year
      old man, which comprised typical features of differentiated teratoma/dermoid cyst
      but which contained a macroscopic rudimentary penis, with vasoformative erectile
      tissue-like structures consistent with corpora cavernosa, as well as scrotal-type
      skin and prostatic tissue. The genitourinary structures were well formed both
      grossly and microscopically and sharply demarcated from the rest of the neoplasm,
      which comprised typical differentiated teratoma, without any other macroscopic
      foci of organoid differentiation or of other histologic differentiation. The
      plasticity of the cells of differentiated teratoma, which enables it to undergo
      multidirectional differentiation, is well recognized, but the factors determining
      this distinct path of differentiation remain to be established.

PMID- 27038685
TI  - Society of Interventional Radiology IR Pre-Procedure Patient Safety Checklist by
      the Safety and Health Committee.

PMID- 27038686
TI  - Independent Analysis of Albumin-Bilirubin Grade in a 765-Patient Cohort Treated
      with Transarterial Locoregional Therapy for Hepatocellular Carcinoma.
AB  - PURPOSE: To assess validity of albumin-bilirubin (ALBI) grade as a predictor of
      survival in patients undergoing transarterial embolization for hepatocellular
      carcinoma. MATERIALS AND METHODS: Baseline albumin and bilirubin values of 765
      consecutive patients treated with conventional transarterial chemoembolization or
      yttrium-90 ((90)Y) radioembolization at a single institution were used to
      determine liver function according to ALBI grade. Survival outcomes were
      stratified by ALBI grade using Kaplan-Meier and stratified by Child-Pugh (C-P)
      class and Barcelona Clinic Liver Cancer (BCLC) stage. Discriminatory ability was
      assessed by C-index. RESULTS: For 428 patients receiving (90)Y radioembolization,
      ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P
      class and BCLC stage, ALBI grade revealed different survival outcomes for C-P B
      (P = .001), BCLC A (P < .001), BCLC B (P = .001), and BCLC C (P < .001). When
      substratified by BCLC stage, ALBI grade was a better discriminator of survival
      than C-P class (C-index 0.792, 0.763, respectively). For 337 patients receiving
      transarterial chemoembolization, ALBI grade yielded distinct survival curves (P <
      .001). When stratified by C-P class and BCLC stage, ALBI grade provided distinct
      survival curves for C-P B (P = .02), BCLC B (P = .001), and BCLC C (P = .02).
      When substratified by BCLC stage, ALBI grade was a better discriminator of
      survival than C-P class (C-index 0.739, 0.735, respectively). CONCLUSIONS: ALBI
      grade outperforms C-P class at discriminating survival in patients receiving
      transarterial chemoembolization or (90)Y radioembolization. ALBI grade is also
      valuable in patients with moderate liver dysfunction and BCLC B disease.

PMID- 27038687
TI  - Endovascular versus Open Repair of Asymptomatic Popliteal Artery Aneurysms: A
      Systematic Review and Meta-Analysis.
AB  - This systematic review compared outcomes between endovascular and open repair of
      asymptomatic popliteal artery aneurysms (PAAs). Endovascular repair was
      associated with increased 30-day graft occlusion (odds ratio [OR] = 3.14; 95%
      confidence interval [CI], 1.43-6.92) and increased 30-day reintervention (OR =
      4.09; 95% CI, 2.79-6.00). The 12-month primary patency rate was significantly
      higher in the open repair group (hazard ratio = 1.95; 95% CI, 1.14-3.33).
      Endovascular repair was associated with shorter length of hospital stay (mean
      difference = -3 d; 95% CI, -4.09 to -1.91; P < .001). Endovascular repair is
      associated with inferior perioperative and postoperative outcomes compared with
      open repair. 

PMID- 27038689
TI  - Follow-up of a patient who had suffered a "heart breaking pleasure"-triggered
      Takotsubo syndrome.

PMID- 27038688
TI  - Sec14-like phosphatidylinositol transfer proteins and the biological landscape of
      phosphoinositide signaling in plants.
AB  - Phosphoinositides and soluble inositol phosphates are essential components of a
      complex intracellular chemical code that regulates major aspects of lipid
      signaling in eukaryotes. These involvements span a broad array of biological
      outcomes and activities, and cells are faced with the problem of how to
      compartmentalize and organize these various signaling events into a coherent
      scheme. It is in the arena of how phosphoinositide signaling circuits are
      integrated and, and how phosphoinositide pools are functionally defined and
      channeled to privileged effectors, that phosphatidylinositol (PtdIns) transfer
      proteins (PITPs) are emerging as critical players. As plant systems offer some
      unique advantages and opportunities for study of these proteins, we discuss
      herein our perspectives regarding the progress made in plant systems regarding
      PITP function. We also suggest interesting prospects that plant systems hold for
      interrogating how PITPs work, particularly in multi-domain contexts, to diversify
      the biological outcomes for phosphoinositide signaling. This article is part of a
      Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo
      Feussner.

PMID- 27038690
TI  - Regarding article, "A multi-artery fractional flow reserve (FFR) approach for
      handling coronary stenosis-stenosis interaction in the multi-vessel disease (MVD)
      arena".

PMID- 27038691
TI  - Electrocardiograms in recurrent multiform epilepsy-triggered Takotsubo syndrome.

PMID- 27038692
TI  - Inconsistency of hemodynamic data in severe aortic stenosis: Yet unexplored
      reasoning!

PMID- 27038693
TI  - An Inflection Point in the Evolution of Oncologic Emergency Medicine.

PMID- 27038694
TI  - Effectiveness of glucagon in relieving esophageal foreign body impaction: a
      multicenter study.
AB  - PURPOSE: Glucagon is thought to decrease lower esophageal sphincter tone and is
      used as an alternative to invasive endoscopy for esophageal foreign body
      impaction (EFBI). The purpose of this study was to evaluate efficacy and safety
      of glucagon and identify characteristics associated with success. METHODS: A
      multicenter, retrospective study of patients receiving glucagon for EFBI at 2
      academic emergency departments was conducted between 2006 and 2010. A control
      group of patients that did not receive glucagon was evaluated. Data collection
      included demographics, type of foreign body, glucagon dose, resolution of
      impaction, incidence of vomiting, additional medication, and endoscopy required.
      Descriptive and univariate analysis was performed as appropriate. RESULTS: A
      total of 133 doses of glucagon were administered in 127 patients. Glucagon
      related resolution of EFBI occurred in 18 patients (14.2%) and vomiting in 16
      patients (12.6%). No statistical differences between successful and unsuccessful
      groups were seen with the exception of concomitant medication administration
      (benzodiazepine or nitroglycerin) being associated with less glucagon success,
      33.3% vs 59.6%, respectively (P = .04). Eighty-four percent of patients in the
      unsuccessful group underwent endoscopy. Comparing those that received glucagon (n
      = 127) and the control group (n = 29), there was no significant difference in
      resolution of EFBI, 14.2% vs 10.3%, respectively (P = .586). CONCLUSIONS:
      Glucagon-related resolution occurred in 14.2% of patients and was not
      significantly different compared with those that did not receive glucagon
      (10.3%). Concomitant medication administration was associated with lower success.
      Overall, glucagon had a low success rate, was related to adverse effects, and
      does not offer advantages for treatment.

PMID- 27038695
TI  - Differential reporting of mixed DNA profiles and its impact on jurists'
      evaluation of evidence. An international analysis.
AB  - While DNA analysis is considered by many the gold standard in forensic science,
      there is ample room for variation in interpretation and reporting. This seems
      especially the case when working with (complex) mixed DNA profiles. Two
      consecutive studies on differential DNA reporting were conducted. In Study 1, we
      first examined type and magnitude of differences when forensic DNA experts across
      institutes and jurisdictions are handed an identical forensic case with mixed
      profiles. In Study 2, we explore the impact of the observed differential
      reporting on jurists' evaluation of the DNA evidence. 19 DNA expert reports from
      forensic institutes across Western jurisdictions were obtained. Differences
      between the reports were many and include extensiveness of the reports,
      explanations of technical issues, use of explanatory appendices, level of
      reporting, use of context information, and, most markedly, type and substantive
      content of the conclusions. In Study 2, a group of criminal law students judged a
      selection of these reports in a quasi experimental study design. Findings show
      that these differing reports have quite different evidentiary value for jurists,
      depending on which expert authored the report. It is argued that the impact of
      differential reporting on jurists' evaluation was so fundamental and substantive
      that it is seems reasonable to claim that in an actual court case it could make
      the difference between acquittal and conviction.

PMID- 27038696
TI  - Neutrophil-to-lymphocyte ratio as a detection marker of tumor recurrence in
      patients with muscle-invasive bladder cancer after radical cystectomy.
AB  - PURPOSE: High-neutrophil to lymphocyte ratio (NLR) values have been shown to be
      associated with a poor prognosis in many human malignant tumors. We evaluated the
      correlation of the NLR with other variables in patients with muscle-invasive
      bladder cancer after radical cystectomy (RC); in particular, we evaluated
      chronological changes in the postoperative NLR. METHODS: We included the data
      from a total of 110 patients who underwent RC for muscle-invasive bladder cancer.
      The NLR was calculated using complete blood counts determined before RC. Kaplan
      Meier and Cox proportional regression analyses of recurrence-free survival (RFS),
      cancer-specific survival (CSS), and overall survival (OS) were performed to
      identify significant prognostic variables. RESULTS: The median patient age was 72
      years (41-91 years). In univariate analysis, the pretreatment NLR (>=2.6 vs.<2.6)
      was associated with RFS (hazard ratio [HR] = 2.41, P = 0.008), CSS (HR = 2.89, P
      = 0.006), and OS (HR = 2.73, P = 0.002). In multivariate analysis, an NLR>=2.6
      and an infiltrative growth pattern at the tumor invasion front were significantly
      associated with RFS (HR = 2.61, P = 0.023), CSS (HR = 2.58, P = 0.08), and OS (HR
      = 2.77, P = 0.004). Postoperative chronological analysis revealed that the NLR of
      68 patients without recurrence remained low during follow-up, whereas the NLR of
      the remaining 42 patients with recurrence increased significantly in the last
      visit before recurrence was detected radiographically (P< 0.01). CONCLUSIONS: The
      NLR and tumor growth pattern were strong predictors of prognosis for patients
      undergoing RC. Our results suggest that an increase in the NLR during follow-up
      after RC is a potential marker for the early detection of recurrence.

PMID- 27038697
TI  - Oncologic surveillance after curative treatment: A probability-based approach
      should be preferred to a risk-based approach.

PMID- 27038698
TI  - Decision analysis model evaluating the cost of a temporary hydrogel rectal spacer
      before prostate radiation therapy to reduce the incidence of rectal
      complications.
AB  - PURPOSE: We conducted a decision analysis to evaluate the cost effectiveness of a
      newly Food and Drug Administration approved rectal spacer gel (SpaceOAR,
      Augmenix) for the reduction of rectal toxicity of prostate radiation therapy
      (RT). METHODS: A decision tree model (TreeAge Pro) was used to compare the
      strategy of pretherapy placement of a spacing hydrogel before RT to RT alone. The
      model compared costs associated with rectal complications because of rectal
      toxicity over a 10-year period across 3 different RT modalities. Rectal toxicity
      rates were estimated from studies on conformal RT dose escalation, high-dose
      stereotactic body radiotherapy (SBRT) and low-dose SBRT. Rectal toxicity
      reduction rates (baseline reduction 70%) were estimated from recently published
      15 month data using a rectal spacer. Direct and indirect cost estimates for
      established grades of rectal toxicity were based on national and institutional
      costs. Reduction in short-term complications were assumed to carry forward to a
      reduction in long-term toxicity. One-way and two-way sensitivity analyses were
      performed. RESULTS: The overall standard management cost for conformal RT was
      $3,428 vs. $3,946 with rectal spacer for an incremental cost of $518 over 10
      years. A 1-way sensitivity analyses showed the breakeven cost of spacer at $2,332
      or a breakeven overall risk reduction of 86% at a cost of $2,850. For high-dose
      SBRT, spacer was immediately cost effective with a savings of $2,640 and
      breakeven risk reduction at 36%. However, 2-way spacer cost to risk reduction
      sensitivity analyses were performed. CONCLUSION: The use of a rectal spacer for
      conformal RT results in a marginal cost increase with a significant reduction in
      rectal toxicity assuming recently published 15 month rectal toxicity reduction is
      maintained over 10 years. For high-dose SBRT it was cost effective. Further
      studies would be necessary to validate the long-term benefits of rectal spacers.

PMID- 27038699
TI  - CDODA-Me decreases specificity protein transcription factors and induces
      apoptosis in bladder cancer cells through induction of reactive oxygen species.
AB  - OBJECTIVE: The objective is to determine whether methyl 2-cyano-3,11-dioxo-18b
      olean-1,12-dien-30-oate (CDODA-Me) has therapeutic potential in bladder cancer.
      We investigated the effects of CDODA-Me on the growth and survival of bladder
      cancer cells, and expression of specificity protein (Sp) transcription factors
      that regulate genes associated with cancer cell proliferation and survival.
      METHODS: J82, RT4P, and 253JB-V bladder cancer cell lines were treated with
      vehicle alone or with CDODA-Me with or without the antioxidant l-glutathione.
      Cell viability and DNA fragmentation were measured by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide-fluorescence
      activated cell sorting (FACS) analysis, respectively. Intracellular reactive
      oxygen species (ROS) were measured by 2',7'-dichlorofluorescin diacetate-FACS
      analysis. We assessed CDODA's effects on the levels of Sp and Sp-regulated
      proteins and induction of apoptosis in bladder cancer cells by Western blotting.
      We also assessed the anticancer effects of CDODA-Me in nude mice bearing RT4v6
      bladder cancer. RESULTS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay and FACS analysis revealed that CDODA-Me inhibited the
      proliferation and survival of the 3 bladder cancer cell lines in a dose-dependent
      manner. FACS analysis also indicated that CDODA-Me-induced intracellular ROS, and
      Western blot analysis indicated that CDODA-Me decreased levels of Sp and Sp
      regulated proteins and induced apoptosis in a dose-dependent and time-dependent
      manner. l-Glutathione attenuated CDODA-Me's down-regulation of Sp and Sp
      regulated proteins. Compared with the control treatment, CDODA-Me substantially
      inhibited tumor growth in vivo. CONCLUSIONS: CDODA-Me has antineoplastic activity
      in bladder cancer cells by inducing ROS, which down-regulate Sp and Sp-regulated
      proteins. Thus, CDODA-Me has therapeutic potential in bladder cancer, and
      additional studies of the agent's efficacy and mode of action are warranted.

PMID- 27038700
TI  - Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal
      muscle sirtuins and heat shock proteins.
AB  - AIM: Sirtuins are proteins that connect energy metabolism, oxidative stress and
      aging. Expression of heat shock proteins (Hsps) is regulated by heat shock
      factors (HSFs) in response to various environmental and physiological stresses,
      such as oxidative stress. Oxidative stress accumulates during aging which makes
      cells more prone to DNA damage. Although many experimental animal models have
      been designed to study the effects of knockdown or overexpression of sirtuins,
      HSFs and Hsps, little is known about how aging per se affects their expression.
      Here we study the impact of intrinsic aerobic capacity, aging and voluntary
      exercise on the levels of sirtuins, HSFs and Hsps in skeletal muscle. METHODS: We
      studied the protein levels of sirtuins (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6
      and SIRT7), HSF1, HSF2, Hsp10, Hsp27 and Hsp70 before and after one-year of
      voluntary running intervention of rat strains selectively bred for intrinsic
      aerobic exercise capacity; high capacity runners (HCR) and low capacity runners
      (LCR) differ by more than 30% for median lifespan. This setup enabled us to
      discern the effects of inborn aerobic capacity, aging and exercise activity on
      the protein levels of sirtuins, HSFs and Hsps in skeletal muscle. RESULTS: Our
      results revealed that the longer lived HCR rats had higher SIRT3, HSF1 and HSF2
      contents in skeletal muscle (gastrocnemius, p < 0.05) than LCRs. Neither aging
      nor voluntary running had a significant effect on the studied sirtuin proteins.
      Aging significantly increased the protein levels of HSF1, HSF2 and Hsp27 (p <
      0.05). CONCLUSION: Our finding of elevated SIRT3 levels in HCR rats is in line
      with previous studies; SIRT3 in general is linked to elevated fatty acid
      oxidation and oxidative phosphorylation, which previously have been associated
      with metabolic profile of HCRs. HSF1, HSF2 and Hsp27 levels increased with aging,
      showing that aged muscles responded to aging-related stress. Our study shows for
      the first time that SIRT3 protein level is linked to high inborn aerobic
      capacity, and may be directly interconnected to longevity.

PMID- 27038701
TI  - Chiral separation of acidic compounds using an O-9-(tert-butylcarbamoyl)quinidine
      functionalized monolith in micro-liquid chromatography.
AB  - An O-9-(tert-butylcarbamoyl) quinidine (t-BuCQD) functionalized polymeric
      monolithic capillary column was prepared by the in situ copolymerization method.
      The physicochemical properties of the optimized monolithic column were
      characterized by scanning electron microscopy and micro-LC. Satisfactory column
      permeability, efficiency, stability and reproducibility were obtained for this
      monolithic column. The chiral recognition ability of the resulting monolith was
      also evaluated using 47 N-derivatized amino acids, eight N-derivatized
      dipeptides, and two herbicides. Under the selected conditions, the enantiomers of
      all chiral analytes were baseline separated with exceptionally high selectivity
      and resolution using micro-LC. It is worth noting that this chiral stationary
      phase (CSP) containing quinidine with a tert-butyl carbamate residue as chiral
      selector exhibits much higher enantioselectivity and diastereoselectivity than
      the previously developed O-9-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11
      dihydroquinidine (MQD) based CSP for N-derivatized amino acids and dipeptides.
      These results indicate that this novel quinidine-based polymeric monolith can be
      used as an effective tool for the enantioseparation of chiral acidic compounds. 

PMID- 27038702
TI  - Analysis of long-term follow-up and examination of pathological liver tissue in
      chronic hepatitis E.
AB  - Hepatitis E is chronic in immunocompromised patients with HIV infection, organ
      transplant, or radiation and chemotherapy. General cases are not chronic. Fifty
      five cases were collected and followed up for 4-14 years. It was found that
      chronic hepatitis E is more common in males, but a high degree of inflammatory
      activity and fibrosis was not evident. After 4-14 years of follow-up observation,
      cirrhosis or liver cancer did not appear. This is significantly different from
      the hepatitis B and C viruses. We speculated that the chronic mechanism in the
      general patients with hepatitis E might be different from that of
      immunocompromised cases. 

PMID- 27038703
TI  - Non-alcoholic steatohepatitis and liver transplantation.
AB  - Non-alcoholic steatohepatitis is a growing liver-related health problem. In
      Europe, non-alcoholic fatty liver disease is the most usual reason of chronic
      liver illness while steatohepatitis, its progressive form, affects 1% of
      Europeans and North Americans. In the United States steatohepatitis-related
      cirrhosis is one of the main indications for liver transplant. A targeted
      stratification for patients waiting for transplant and affected by this disease
      is mandatory especially because of their increased cardiovascular and cancer
      risk. The adequate treatment of NAFLD is crucial for the reduction of the disease
      related morbidity and mortality. In post-transplant setting, the recurrent or de
      novo steatosis might seriously affect the allograft short- and long-term outcome.
      Many conditions can represent the basis of the post-transplant steatohepatitis:
      obesity, hyperlipidaemia, diabetes mellitus, arterial hypertension,
      immunosuppressant treatment, alcoholic habit and liver graft steatosis. Today,
      the only consolidated therapy is represented by a deep life-style intervention
      since the use of drug-based alternative strategies is still limited and a very
      few data are available for the post-transplant period. Targeted and personalized
      behaviour and pharmacological interventions have to be developed for both the pre
      and post-transplant phase. 

PMID- 27038704
TI  - Reply to "When to resume anticoagulation after acute gastrointestinal bleeding?".

PMID- 27038705
TI  - Immunoglobulin G4 (IgG4)-associated pouchitis - Part of IgG4 related disease? A
      case series and review of the literature.
AB  - BACKGROUND AND AIMS: IgG4-mediated pouchitis was first described in 2011. The
      aetiology and pathogenesis of IgG4-associated pouchitis is unknown. Over the last
      four years, less than seventy cases of IgG-associated pouchitis have been
      reported from a pouchitis clinic in Cleveland. METHODS: We report the first two
      cases of IgG4-associated pouchitis from our inflammatory bowel disease clinic and
      outside of Cleveland. CONCLUSION: This highlights the fact that this entity could
      be more common than we think. It is important for general gastroenterologists to
      think about IgG4-mediated disease if the patient has refractory pouchitis, so
      early diagnosis and referral can be made. This would avoid the cost of expensive
      therapy and minimize antibiotic use which is what happened in our cases prior to
      this diagnosis being made.

PMID- 27038706
TI  - Difficulty of Comparing the Multiple Heterogeneous Approaches: Comment to
      Transcranial Direct Current Stimulation in Epilepsy.

PMID- 27038707
TI  - Effects of 10 Hz and 20 Hz Transcranial Alternating Current Stimulation on
      Automatic Motor Control.
AB  - BACKGROUND: In a masked prime choice reaction task, presentation of a compatible
      prime increases the reaction time to the following imperative stimulus if the
      interval between mask and prime is around 80-250 ms. This is thought to be due to
      automatic suppression of the motor plan evoked by the prime, which delays
      reaction to the imperative stimulus. Oscillatory activity in motor networks
      around the beta frequency range of 20 Hz is important in suppression of movement.
      Transcranial alternating current at 20 Hz may be able to drive oscillations in
      the beta range. OBJECTIVE/HYPOTHESIS: To investigate whether transcranial
      alternating current stimulation (tACS) at 20 Hz would increase automatic
      inhibition in a masked prime task. As a control we used 10 Hz tACS. METHODS:
      Stimulation was delivered at alpha (10 Hz) and beta (20 Hz) frequency over the
      supplementary motor area and the primary motor cortex (simultaneous tACS of SMA
      M1), which are part of the BG-cortical motor loop, during the execution of the
      subliminal masked prime left/right choice reaction task. We measured the effects
      on reaction times. Corticospinal excitability was assessed by measuring the
      amplitude of motor evoked potentials (MEPs) evoked in the first dorsal
      interosseous muscle by transcranial magnetic stimulation (TMS) over M1. RESULTS:
      The 10 and 20-Hz tACS over SMA-M1 had different effects on automatic inhibition.
      The 20 Hz tACS increased the duration of automatic inhibition whereas it was
      decreased by 10 Hz tACS. Neurophysiologically, 20 Hz tACS reduced the amplitude
      of MEPs evoked from M1, whereas there was no change after 10 Hz tACS. CONCLUSION:
      Automatic mechanisms of motor inhibition can be modulated by tACS over motor
      areas of cortex. tACS may be a useful additional tool to investigate the causal
      links between endogenous brain oscillations and specific cognitive processes.

PMID- 27038708
TI  - Current Concepts in Osteoradionecrosis after Head and Neck Radiotherapy.
AB  - Osteoradionecrosis (ORN) of the jaws is a feared complication of head and neck
      radiotherapy. ORN causes significant morbidity for patients and controversy among
      clinicians. This overview considers the variations in definition and
      classification of the condition that affect estimates of incidence and also the
      interpretation of evidence. The influence of newer radiotherapy techniques in
      reducing ORN through reduced dose and xerostomia is balanced against a probable
      increase in a vulnerable population through a rising head and neck cancer
      incidence. Theories of pathophysiology of ORN include radiation-induced
      osteomyelitis, hypoxic and hypovascular theory and fibroatrophic theory.
      Prevention strategies include restorative dentistry and radiation planning
      techniques. Treatments range from conservative 'watch and wait' through to more
      radical surgical strategies. Newer medical management strategies are available
      with a limited evidence base. The use of hyperbaric oxygen therapy remains
      controversial and the background and need for newer hyperbaric oxygen trials is
      discussed. 

PMID- 27038709
TI  - Molecular characterization and prevalence of two capulaviruses: Alfalfa leaf curl
      virus from France and Euphorbia caput-medusae latent virus from South Africa.
AB  - Little is known about the prevalence, diversity, evolutionary processes, genomic
      structures and population dynamics of viruses in the divergent geminivirus
      lineage known as the capulaviruses. We determined and analyzed full genome
      sequences of 13 Euphorbia caput-medusae latent virus (EcmLV) and 26 Alfalfa leaf
      curl virus (ALCV) isolates, and partial genome sequences of 23 EcmLV and 37 ALCV
      isolates. While EcmLV was asymptomatic in uncultivated southern African Euphorbia
      caput-medusae, severe alfalfa disease symptoms were associated with ALCV in
      southern France. The prevalence of both viruses exceeded 10% in their respective
      hosts. Besides using patterns of detectable negative selection to identify ORFs
      that are probably functionally expressed, we show that ALCV and EcmLV both
      display evidence of inter-species recombination and biologically functional
      genomic secondary structures. Finally, we show that whereas the EcmLV populations
      likely experience restricted geographical dispersion, ALCV is probably freely
      moving across the French Mediterranean region.

PMID- 27038710
TI  - Intravenous iron sucrose reverses anemia-induced cardiac remodeling, prevents
      myocardial fibrosis, and improves cardiac function by attenuating
      oxidative/nitrosative stress and inflammation.
AB  - BACKGROUND: According to recent clinical trial data, correction of iron
      deficiency with intravenous (i.v.) iron has favorable outcomes on cardiac
      function. We evaluated whether i.v. iron treatment of anemic rats has favorable
      effect on the left ventricular (LV) performance and remodeling and the role of
      oxidative/nitrosative stress and inflammation in the process. METHODS: After
      weaning, Sprague-Dawley rats were fed low iron diet for 16weeks, after which the
      treatment group received five weekly doses of i.v. iron sucrose (10mg Fe/kg body
      weight). Echocardiography of LV was performed and hematology parameters were
      assessed before treatment (baseline, day 0) and at the end of the study (day 29).
      On day 29, rats were sacrificed and extracellular expansion and fibrosis in LV
      and interventricular septum were evaluated together with oxidative/nitrosative
      stress, pro-inflammatory, and repair process markers. RESULTS: Although iron
      sucrose treatment did not fully correct the anemia, it reversed anemia-induced
      cardiac remodeling as indicated by echocardiographic and tissue Doppler
      parameters. Treatment with iron sucrose also prevented anemia-induced myocardial
      fibrosis as indicated by extracellular expansion and fibrosis markers. Anemia
      induced inflammation was prevented by iron sucrose as indicated by the levels of
      proinflammatory (TNF-alpha, NF-kappaB65) and repair process markers (HSP27,
      HSP70). In addition, iron sucrose treatment significantly reduced (p<0.01) anemia
      induced oxidative and nitrosative stress. CONCLUSION: Intravenous iron sucrose
      treatment reversed anemia-induced remodeling of LV, prevented myocardial
      fibrosis, and improved cardiac function by attenuating oxidative/nitrosative
      stress and inflammation in the heart.

PMID- 27038711
TI  - Bifurcation lesions: Bioresorbable vascular scaffold and drug coated balloon, an
      efficacy association. Lessons from optimal coherence tomography.

PMID- 27038712
TI  - Differentiation of cardiac thrombus from cardiac tumor combining cardiac MRI and
      18F-FDG-PET/CT Imaging.
AB  - Radiological differentiation of an unknown cardiac masse is often a challenging
      issue. 18F-FDG-PET/CT imaging was performed to evaluate a left ventricle mass
      visualized on transthoracic echocardiogram (TTE) and cardiac magnetic resonance
      (CMR) in a patient with an history of ischemic heart disease. The metabolically
      inert area on the PET/CT, corresponding to the relatively homogenous hypodensity
      in the LV, was thought to represent an old organized LV thrombus.
      Histopathological examination confirmed the imaging diagnosis. 

PMID- 27038713
TI  - Is the new Micra-leadless pacemaker entirely safe?

PMID- 27038714
TI  - Role of stent type and of duration of dual antiplatelet therapy in patients with
      chronic kidney disease undergoing percutaneous coronary interventions. Is bare
      metal stent implantation still a justifiable choice? A post-hoc analysis of the
      all comer PRODIGY trial.
AB  - AIM: Chronic kidney disease (CKD) is a powerful predictor of major cardiovascular
      events and stent thrombosis (ST) in patients undergoing percutaneous coronary
      interventions (PCI). No randomized data are available to compare, and guide the
      selection of type of stent between bare metal (BMS) or drug eluting stent (DES)
      in this population. METHODS AND RESULTS: We performed a post-hoc analysis of the
      PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal
      hyperplasia studY (PRODIGY) trial, in which stable or unstable patients with
      coronary artery disease undergoing PCI were randomized 1:1:1:1 to receive BMS,
      paclitaxel- (PES), zotarolimus- (ZES-S), or everolimus- (EES) eluting stent. A
      total of 2003 patients were randomized, and 22 patients were excluded for missing
      serum creatinine leading to a final population of 1981 patients. Primary outcome
      was definite or probable ST. We also assessed MACE (myocardial infarction,
      stroke, or death), and all-cause death, as secondary outcome. CKD, defined with
      estimated glomerular filtration rate <60ml/min/1.73m(2), was found in 373
      patients (18.8%). The incidence of ST at 2years was 5.1% in CKD and 2.1% in non
      CKD patients (HR 2.57, 95% confidence interval (CI) 1.46 to 4.52, p<0.001). At
      multivariable regression we found that patients randomized to EES or ZES-S, but
      not PES, had lower risk of ST at two years as compared with BMS: adjusted
      HR=0.288, 95% CI [0.107-0.778, p=0.014] and HR=0.394, 95% CI [0.164-0.947,
      p=0.037] respectively. The number of patients needed to be treated to prevent 1
      ST with an EES vs BMS was 20 in CKD and 50 in patients without CKD. EES patients
      had the lowest incident MACE events 26.4% as compared to BMS 35.1%, ZES-S 33.0%,
      or PES 35.7% patients, p=0.551. All-cause death was lowest in ZES-S group 10.6%
      as compared to BMS 18.1%, PES 25.5% and EES 14.9%, p=0.040. We found no
      significant interaction between DAPT duration (6 vs 24months) and stent type on
      primary outcome, PINT=0.47 for BMS, PINT=0.57 for PES, PINT=0.41 for ZES-S and
      PINT=0.28 for EES. CONCLUSIONS: In an all-comer population of patients with
      stable and unstable CAD, CKD at baseline was associated with a double risk of ST
      and MACE. CKD patients receiving EES had less than half risk of ST 2years after
      PCI as compared with BMS and PES. Our analysis suggests that 2nd generation limus
      based stent should be favored over paclitaxel-based DES or BMS to reduce ST and
      MACE in CKD patients.

PMID- 27038715
TI  - Loss of TLR4 in a murine model of left anterior descending myocardial infarction
      modifies early remodeling, but does not provide long-term benefit.

PMID- 27038716
TI  - Intricate associations between heart failure, depression and vitamin D.

PMID- 27038717
TI  - A glimpse into first generation drug-eluting and bare metal stents ten years
      later with optical coherence tomography analysis.

PMID- 27038718
TI  - Coffee consumption and risk of cardiovascular events in hypertensive patients.
      Results from the HARVEST.
AB  - BACKGROUND: Controversy still exists about the long-term cardiovascular effects
      of coffee consumption in hypertension. METHODS: The predictive capacity of coffee
      use for cardiovascular events (CVEs) was investigated in 1204 participants from
      the HARVEST, a prospective cohort study of non-diabetic subjects aged 18-45years,
      screened for stage 1 hypertension. Subjects were grouped into three categories of
      coffee drinking, non-drinkers (none), moderate drinkers (1 to 3cups/day) and
      heavy drinkers (4or more cups/day). Multivariate Cox proportional hazards models
      were developed adjusting for possible confounding variables and risk factors.
      RESULTS: During a median follow-up of 12.6years, CVEs were developed by 60
      participants. CVEs were more common among coffee drinkers than abstainers
      (abstainers, 2.2%; moderate drinkers, 7.0%; heavy drinkers, 14.0%; p for
      trend=0.0003). In a multivariable Cox regression model, coffee use was a
      significant predictor of CVE in both coffee categories, with a hazard ratio of
      2.8 (95% CI, 1.0-7.9) in moderate coffee drinkers and of 4.5 (1.4-14.2) in heavy
      drinkers compared to abstainers. After inclusion of change in body weight (p=ns),
      incident hypertension (p=0.027) and presence of diabetes/prediabetes (p=ns) at
      follow-up end, the association with CVE was attenuated but remained significant
      in heavy coffee drinkers (HR, 95% CI, 3.4, 1.04-11.3). CONCLUSIONS: These data
      show that coffee consumption increases the risk of CVE in a linear fashion in
      hypertension. This association may be explained in part by the association
      between coffee and development of hypertension. Hypertensive patients should be
      discouraged from drinking coffee.

PMID- 27038719
TI  - Clinical outcomes for transcatheter valve-in-valve in treating surgical
      bioprosthetic dysfunction: A meta-analysis.

PMID- 27038720
TI  - The impact of marital status on mortality and length of stay in patients admitted
      with acute coronary syndrome.

PMID- 27038721
TI  - Pseudoaneurysm with fistulization to the left atrium: A very rare late
      complication of previous aortic root surgery.

PMID- 27038722
TI  - Simultaneous subacute coronary artery stent thrombosis in a carrier of two
      CYP2C19 loss-of function polymorphisms (*2/*3).

PMID- 27038723
TI  - Association between age, time after hospitalization, and survival among patients
      hospitalized for acute heart failure syndromes.

PMID- 27038724
TI  - Intravascular ultrasound for morphological assessment of napkin-ring sign
      detected on multidetector computed tomography.
AB  - BACKGROUND: Although napkin-ring sign (NRS) plaques assessed by multidetector
      computed tomography (MDCT) is identified as a high-risk feature, the detailed
      morphological features are still unknown. The purpose of this study was to
      elucidate the morphological features of the MDCT-assessed NRS using intravascular
      ultrasound (IVUS). METHODS: We evaluated 204 plaques in 193 patients with non-ST
      elevation acute coronary syndrome who were diagnosed using 128-slice MDCT and
      were assessed using IVUS prior to coronary intervention. Morphology was compared
      between plaques with and without MDCT-assessed NRS. Severe IVUS-assessed
      attenuation was defined as an attenuation angle >180 degrees . RESULTS: NRS was
      detected in 49 lesions. MDCT-assessed plaque attenuation was lower (p<0.0001),
      and cross-sectional plaque areas at lesion sites, remodeling index, and the
      prevalence of positive remodeling were greater, in lesions with NRS (p<0.005,
      p<0.0001, and p<0.0001, respectively). Furthermore, the IVUS-assessed remodeling
      index and prevalence of severe attenuation and speckled echo appearance were
      significantly greater in lesions with NRS (p<0.01, p<0.0001, and p<0.0001,
      respectively). Using multivariate analysis, IVUS-assessed speckled echo
      appearance was identified as an independent predictor of MDCT-assessed NRS (odds
      ratio, 3.59; 95% confidence interval, 1.49-8.66; p<0.005). CONCLUSION: MDCT
      assessment of NRS may be associated with larger heterogeneous necrotic cores and
      greater positive remodeling.

PMID- 27038725
TI  - Effects of statin therapy on augmentation index as a measure of arterial
      stiffness: A systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effects of statin therapy on augmentation index (AIx)
      as a measure of arterial stiffness using a meta-analysis of clinical trials.
      METHODS: The search included PubMed-Medline, Embase, SCOPUS, Web of Science and
      Google Scholar databases to identify randomized controlled trials investigating
      the effects of statin therapy on arterial stiffness measured as AIx. A random
      effects model and generic inverse variance method were used for quantitative data
      synthesis. Sensitivity analysis was conducted using the leave-one-out method.
      Random-effects meta-regression was performed using unrestricted maximum
      likelihood method to evaluate the impact of potential confounders. RESULTS: 18
      trials examining the effects of statin therapy on arterial stiffness were
      included. A significant reduction in aortic AIx following statin therapy was
      proven (WMD: -2.40%, 95% CI: -4.59, -0.21, p=0.032; I(2): 51.20%). HR-adjusted
      AIx 75% values also revealed a significant improvement by statin therapy (WMD: 
      5.04%, 95% CI: -7.81, -2.27, p<0.001; I(2): 0%), but not when analysis was
      restricted to unadjusted AIx values (WMD: -2.30%, 95% CI: -4.83, 0.23, p=0.075;
      I(2): 53.83%). There was no significant change in carotid (WMD: -2.75%, 95% CI: 
      8.06, 2.56, p=0.309; I(2): 26.86%) and peripheral (WMD: 0.25%, 95% CI: -3.31,
      3.82, p=0.889; I(2): 72.19%) AIx due to statin treatment. There was also no
      difference in the effect size calculated for different statins subgroups. The
      impact of statins on AIx was independent of LDL-cholesterol level (slope: 0.05;
      95% CI: -0.02, 0.13; p=0.181). CONCLUSION: Statin therapy causes a significant
      reduction in aortic AIx which is independent of LDL-cholesterol changes.

PMID- 27038726
TI  - Arrhythmic risk prediction of acute myocarditis presenting with life-threatening
      ventricular tachyarrhythmias.

PMID- 27038727
TI  - Medication adherence to rivaroxaban and dabigatran for stroke prevention in
      patients with non-valvular atrial fibrillation in the United States.

PMID- 27038728
TI  - The role of epigenetic modifications in cardiovascular disease: A systematic
      review.
AB  - BACKGROUND: Epigenetic modifications of the genome, such as DNA methylation and
      histone modifications, have been reported to play a role in processes underlying
      cardiovascular disease (CVD), including atherosclerosis, inflammation,
      hypertension and diabetes. METHODS: Eleven databases were searched for studies
      investigating the association between epigenetic marks (either global, site
      specific or genome-wide methylation of DNA and histone modifications) and CVD.
      RESULTS: Of the 3459 searched references, 31 studies met our inclusion criteria
      (26 cross-sectional studies and 5 prospective studies). Overall, 12,648
      individuals were included, with total of 4037 CVD events. The global DNA
      methylation assessed at long-interspersed nuclear element (LINE-1) was inversely
      associated with CVD, independent of established cardiovascular risk factors.
      Conversely, a higher degree of global DNA methylation measured at Alu repeats or
      by the LUMA method was associated with the presence of CVD. The studies reported
      epigenetic regulation of 34 metabolic genes (involved in fetal growth, glucose
      and lipid metabolism, inflammation, atherosclerosis and oxidative stress) in
      blood cells to be related with CVD. Among them, 5 loci were validated and
      methylation at F2RL3 was reported in two large prospective studies to predict
      cardiovascular disease beyond the traditional risk factors. CONCLUSIONS: Current
      evidence supports an association between genomic DNA methylation and CVD.
      However, this review highlights important gaps in the existing evidences
      including lack of large-scale epigenetic investigations, needed to reliably
      identify genomic loci where DNA methylation is related to risk of CVD.

PMID- 27038729
TI  - Incessant pericarditis following dual-chamber cardioverter defibrillation device
      implantation.

PMID- 27038730
TI  - The PARADIGM of ARNI's: Assessing reasons for non-implementation in heart
      failure.
AB  - Several trials have targeted neutral endopeptidase to demonstrate benefits for
      patients with heart failure. In the PARADIGM-HF trial, a combination of
      sacubitril and valsartan was superior to enalapril in reducing the risk of death
      and of hospitalization for heart failure. In this editorial we apply the trial to
      heart failure population at large to estimate what proportion of patients might
      actually be treated in daily practice. 

PMID- 27038731
TI  - Respiratory function and oxygenation after balloon pulmonary angioplasty.

PMID- 27038732
TI  - Falling cholesterol trend at acute coronary syndrome presentation is strongly
      related to statin use for secondary prevention.
AB  - BACKGROUND: Lifestyle changes are believed responsible for temporal trends of
      reduced population total cholesterol (TC), but it is uncertain whether this
      applies to patients with known coronary heart disease (CHD) often prescribed
      lipid lowering therapy (LLT). We studied temporal TC trends at presentation with
      acute coronary syndrome (ACS) to determine the contribution of LLT given for
      secondary prevention. METHODS: TC and LLT were obtained in 5592 patients in
      annual surveys of ACS admissions in Australia between 1999 and 2013, and annual
      mean trends analysed by linear and segmented regression. RESULTS: TC declined
      from 5.13+/-1.1 to 4.53+/-1.2mmol/L (p<0.001) and LLT (96% statin) use at
      presentation increased from 37.4% to 47.5% (p=0.005). TC decline was greater in
      those on LLT vs. those not on therapy, with LLT contributing to 57% of the TC
      decline. The decline in TC and increase in LLT use was non-linear and much
      steeper in those with, than without CHD history, and LLT contributed
      substantially more to the TC decline (79%, p<0.001 vs. 27%, p=0.06 respectively).
      The rapid decline in TC and increase in LLT, plateauing after 2005 in those with
      CHD history differed markedly from trends in recent population studies, while TC
      trend for those without CHD history was slower, linear and consistent with
      population trends. CONCLUSIONS: Declining TC level at presentation for ACS was
      strongly associated with increasing LLT use in those with a history of CHD,
      indicating that increasing uptake of LLT for secondary prevention has impacted TC
      changes in the new millennium.

PMID- 27038733
TI  - Clinical confirmation of impending left ventricular rupture.

PMID- 27038734
TI  - Occupant UV exposure measurements for upper-room ultraviolet germicidal
      irradiation.
AB  - The threshold limit value (TLV) guideline for ultraviolet (UV) radiation
      specifies that irradiance measurements to ensure occupant safety be taken over an
      angle of 80 degrees  at the sensor. The purpose of this study was to evaluate the
      effect of an 80 degrees  field of view (FOV) tube on lower room UV-C irradiation
      measurements. Measurements were made in an experimental chamber at a height of
      1.73m with and without an FOV tube. The FOV tube reduced the lower room
      irradiance readings by 18-34%, a statistically significant reduction compared to
      the bare sensor. An 80 degrees  FOV tube should be used for lower room irradiance
      measurements to comply with the TLV guideline. The resulting lower readings would
      allow more UV-C radiation in the upper room without compromising occupant safety.
      More UV-C radiation in the upper room could increase efficacy of UVGI systems for
      reducing transmission of airborne infectious diseases. In addition,
      recommendations are made to standardize lower room irradiance measurement
      techniques. 

PMID- 27038735
TI  - Liraglutide protects cardiac microvascular endothelial cells against
      hypoxia/reoxygenation injury through the suppression of the SR-Ca(2+)-XO-ROS axis
      via activation of the GLP-1R/PI3K/Akt/survivin pathways.
AB  - Microvascular endothelial cells (CMECs) oxidative damage resulting from
      hypoxia/reoxygenation (H/R) injury is responsible for microcirculation perfusion
      disturbances and the progression of cardiac dysfunction. However, few strategies
      are available to reverse such pathologies. Here, we studied the effects and
      mechanisms of liraglutide on CEMCs oxidative damage, focusing in particular on
      calcium overload-triggered free radical injury signals and the GLP
      1R/PI3K/Akt/survivin survival pathways. The results indicate that H/R increased
      IP3R expression but reduced SERCA2a expression, which rapidly raised
      intracellular Ca(2+) levels, subsequently leading to Ca(2+)-dependent xanthine
      oxidase (XO) activation, reactive oxygen species (ROS) production and the
      cellular apoptosis of CMECs. However, liraglutide pretreatment abrogated Ca(2+)
      mediated oxidative apoptosis. Furthermore, liraglutide regulated the rate of
      IP3R/SERCA2a gene transcription and conserved SERCA2a-ATPase activity via the
      maintenance of ATP production under H/R, which drove excessive Ca(2+) reflux to
      the sarcoplasmic reticulum (SR) and inhibited Ca(2+) release from the SR,
      ultimately restoring Ca(2+) homeostasis. Furthermore, the regulatory role of
      liraglutide on Ca(2+) balance in conjunction with its up-regulation of superoxide
      dismutase, glutathione and glutathione peroxidase collectively scavenged the
      excess ROS under H/R. Moreover, we showed that liraglutide strengthened Akt
      phosphorylation and subsequently survivin expression. In addition, both the
      blockade of the GLP-1R/PI3K/Akt pathways and the siRNA-mediated knockdown of
      survivin abolished the protective effects of liraglutide on SR-Ca(2+) function
      and CMECs oxidative apoptosis. In summary, this study confirmed that H/R induced
      CMECs oxidative damage through the SR-Ca(2+)-XO-ROS injury signals and that
      liraglutide pretreatment may suppress such CMECs damage through the
      PI3K/Akt/survivin pathways.

PMID- 27038736
TI  - Oysters and Vibrios as a Model for Disease Dynamics in Wild Animals.
AB  - Disease dynamics in the wild are influenced by a number of ecological and
      evolutionary factors not addressed by traditional laboratory-based
      characterization of pathogens. Here we propose the oyster, Crassostrea gigas, as
      a model for studying the interaction of the environment, bacterial pathogens, and
      the host in disease dynamics. We show that an important first step is to ask
      whether the functional unit of pathogenesis is a bacterial clone, a population,
      or a consortium in order to assess triggers of disease outbreaks and devise
      appropriate monitoring tools. Moreover, the development of specific-pathogen-free
      (SPF) oysters has enabled assessment of the infection process under natural
      conditions. Finally, recent results show the importance of microbial interactions
      and host genetics in determining oyster health and disease.

PMID- 27038737
TI  - Finding the optimal deconvolution algorithm for MR perfusion in carotid stenosis:
      Correlations with angiographic cerebral circulation time.
AB  - PURPOSE: The aim of our study is to explore the impacts of different
      deconvolution algorithms on correlations between CBF, MTT, CBV, TTP, Tmax from MR
      perfusion (MRP) and angiography cerebral circulation time (CCT). METHODS:
      Retrospectively, 30 patients with unilateral carotid stenosis, and available pre
      stenting MRP and angiography were included for analysis. All MRPs were conducted
      in a 1.5-T MR scanner. Standard singular value decomposition, block-circulant,
      and two delay-corrected algorithms were used as the deconvolution methods. All
      angiographies were obtained in the same bi-plane flat-detector angiographic
      machine. A contrast bolus of 12mL was administrated via angiocatheter at a rate
      of 8mL/s. The acquisition protocols were the same for all cases. CCT was defined
      as the difference between time to peak from the cavernous ICA and the parietal
      vein in lateral view. Pearson correlations were calculated for CCT and CBF, MTT,
      CBV, TTP, Tmax. RESULTS: The correlation between CCT and MTT was highest with
      Tmax (r=0.65), followed by MTT (r=0.60), CBF (r=-0.57), and TTP (r=0.33) when
      standard singular value decomposition was used. No correlation with CBV was
      noted. CONCLUSIONS: MRP using a singular value decomposition algorithm confirmed
      the feasibility of quantifying cerebral blood flow deficit in steno-occlusive
      disease within the angio-room. This approach might further improve patient safety
      by providing immediate cerebral hemodynamics without extraradiation and iodine
      contrast.

PMID- 27038738
TI  - Seeing the unseen: Second-order correlation learning in 7- to 11-month-olds.
AB  - We present four experiments with the object-examining procedure that investigated
      7-, 9-, and 11-month-olds' ability to associate two object features that were
      never presented simultaneously. In each experiment, infants were familiarized
      with a number of 3D objects that incorporated different correlations among the
      features of those objects and the body of the objects (e.g., Part A and Body 1,
      and Part B and Body 1). Infants were then tested with objects with a novel body
      that either possessed both of the parts that were independently correlated with
      one body during familiarization (e.g., Part A and B on Body 3) or that were
      attached to two different bodies during familiarization. The experiments
      demonstrate that infants as young as 7months of age are capable of this kind of
      second-order correlation learning. Furthermore, by at least 11months of age
      infants develop a representation for the object that incorporates both of the
      features they experienced during training. We suggest that the ability to learn
      second-order correlations represents a powerful but as yet largely unexplored
      process for generalization in the first years of life.

PMID- 27038739
TI  - Relationship between the target dose for hemodialysis adequacy and nutritional
      assessment.
AB  - BACKGROUND: Some studies have shown an increased relative risk of death for
      patients with higher levels of Kt/V, which may be associated with marked
      malnutrition. OBJECTIVE: The aim of this study was to investigate the
      relationship between the target dose for hemodialysis adequacy, as measured by
      Kt/V, and various nutritional parameters in hemodialysis patients. DESIGN: Cross
      sectional. SETTINGS: Sakarya University Faculty of Medicine, Turkey between
      February 2014 and March 2014. PATIENTS AND METHODS: For consecutive patients who
      met criteria, the following were recorded: nutritional status, dialysis
      malnutrition score (DMS), the geriatric nutritional risk index (GNRI), serum
      albumin level, anthropometric measurements, and bioelectrical impedance analysis.
      Patients were classified into two groups according to the target hemodialysis
      dose for single-pool Kt/V: patients with spKt/V >=1.4 and patients with spKt/V <
      1.4. MAIN OUTCOME MEASURE(S): Association of hemodialysis adequacy by nutritional
      assessment. RESULTS: The prevalence of malnutrition in 286 patients with target
      dose hemodialysis (spKt/V >=1.4) was significantly higher according to body mass
      index (BMI), DMS, and GDRI (P=.001, P=.006, and P=.004, respectively) compared
      with patients with a lower target dose (spKt/V < 1.4). BMI, biceps skinfolds, mid
      arm circumference, calf circumference, fat free mass, and total body water were
      statistically significantly lower in patients at a higher target dose (spKt/V >=
      1.4) (P < .001, P=.034, P=.010, P < .001, P < .001, and P < .001 respectively).
      CONCLUSIONS: Malnutrition was more frequent in chronic hemodialysis patients who
      received the target hemodialysis. Evaluation of nutritional status in patients at
      the target hemodialysis dose should be considered. LIMITATIONS: Data collected
      from a single region; small sample size; cross-sectional design is
      disadvantageous.

PMID- 27038740
TI  - Angiotensin IV protects cardiac reperfusion injury by inhibiting apoptosis and
      inflammation via AT4R in rats.
AB  - Angiotensin IV (Ang IV) is formed by aminopeptidase N from Ang III by removing
      the first N-terminal amino acid. Previously, we reported that Ang III has some
      cardioprotective effects against global ischemia in Langendorff heart. However,
      it is not clear whether Ang IV has cardioprotective effects. The aim of the
      present study was to evaluate the effect of Ang IV on myocardial ischemia
      reperfusion (I/R) injury in rats. Before ischemia, male Sprague-Dawley rats
      received Ang IV (1mg/kg/day) for 3 days. Anesthetized rats were subjected to
      45min of ischemia by ligation of left anterior descending coronary artery
      followed by reperfusion and then, sacrificed 1 day or 1 week after reperfusion.
      Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations, and
      infarct size were measured. Quantitative analysis of apoptotic and inflammatory
      proteins in ventricles were performed using Western blotting. Pretreatment with
      Ang IV attenuated I/R-induced increases in plasma CK and LDH levels, and infarct
      size, which were blunted by Ang IV receptor (AT4R) antagonist and but not by
      antagonist for AT1R, AT2R, or Mas receptor. I/R increased Bax, caspase-3 and
      caspase-9 protein levels, and decreased Bcl-2 protein level in ventricles, which
      were blunted by Ang IV. I/R-induced increases in TNF-alpha, MMP-9, and VCAM-1
      protein levels in ventricles were also blunted by Ang IV. Ang IV increased the
      phosphorylation of Akt and mTOR. These effects were attenuated by co-treatment
      with AT4R antagonist or inhibitors of downstream signaling pathway. Myocardial
      dysfunction after reperfusion was improved by Ang IV. These results suggest that
      Ang IV has cardioprotective effect against I/R injury by inhibiting apoptosis via
      AT4R and PI3K-Akt-mTOR pathway.

PMID- 27038741
TI  - PAI-1 deficiency increases the trophic effects of hypergastrinemia in the gastric
      corpus mucosa.
AB  - The gastric hormone gastrin plays a role in organizing the gastric mucosa.
      Gastrin also regulates the expression of genes that have important actions in
      extracellular matrix modelling, including plasminogen activator inhibitor (PAI)-1
      which is part of the urokinase plasminogen activator (uPA) system. The uPA system
      (including PAI-1) is associated with cancer progression, fibrosis and thrombosis.
      Its biological role in the stomach and molecular mechanisms of action are not
      well understood. The aim of this study was to examine the effect of PAI-1 on the
      trophic changes observed in gastric corpus mucosa in hypergastrinemia using PAI-1
      and/or HK-ATPase beta subunit knockout (KO) mice. HK-ATPase beta subunit KO mice
      were used as a model of hypergastrinemia. In 12 month old female mice,
      intragastric acidity and plasma gastrin were measured. The stomachs were examined
      for macroscopic and histological changes. In mice null for both PAI-1 and HK
      ATPase beta (double KO), there was exaggerated hypergastrinemia, increased
      stomach weight and corpus mucosal thickness, and more pronounced trophic and
      architectural changes in the corpus compared with HK-ATPase beta KO mice. Genome
      wide microarray expression data for the gastric corpus mucosa showed a distinct
      gene expression profile for the HK-ATPase beta KO mice; moreover, enrichment
      analysis revealed changes in expression of genes regulating intracellular
      processes including cytoskeleton remodelling, cell adhesion, signal transduction
      and epithelial-to-mesenchymal transition (EMT). Genes differentially expressed in
      the double KO compared with HK-ATPase beta KO mice included the transcription
      factor Barx2 and the chromatin remodeler gene Tet2, which may be involved in both
      normal gastric physiology and development of gastric cancer. Based on the present
      data, we suggest that PAI-1 plays a role in maintaining gastric mucosal
      organization in hypergastrinemia.

PMID- 27038742
TI  - Neuronal correlates of sustained fear in the anterolateral part of the bed
      nucleus of stria terminalis.
AB  - As part of the extended amygdala network, the bed nucleus of the stria terminalis
      (BNST) was shown to be critically involved in processing sustained fear responses
      to diffuse and unpredictable threats. However, neuronal activity patterns in
      relation to sustained components of the fear response remain elusive, so far. We
      used a fear training paradigm with unpredictable pairing of conditioned and
      unconditioned stimuli allowing distinction between phasic and sustained
      components of conditioned fear, and recorded single units in the anterolateral
      part of the BNST (BNSTal) in freely behaving mice. An objective, non-biased
      cluster-analysis was performed for each identified single unit on specific
      waveform-, activity-, stimulus-dependent and LFP-related parameters. The analysis
      revealed three distinct neuronal subpopulations of biphasic-, sustained fear on-
      and fear off-neurons. Results show that activities of biphasic- and sustained
      fear on-neurons temporally coincide with the shift from phasic to sustained
      components of the fear response. Presentation of non-conditioned auditory stimuli
      resulted in a variety of neuronal responses in BNSTal with no indication of
      biphasic response profiles. It is suggested that fear conditioning sharpens
      neuronal response profiles in BNSTal with biphasic-cells signaling phasic and
      sustained fear. These results confirm the pivotal role of BNST in processing
      sustained fear on the neuronal level, thereby complementing pharmacological
      experimental animal and human imaging data.

PMID- 27038743
TI  - Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal
      CA1 neurons during locomotor activity and sleep.
AB  - The activity-regulated cytoskeletal-associated protein/activity regulated gene
      (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation.
      However, the neurophysiological substrates of memory deficits occurring in the
      absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1 single-unit and
      local field potential (LFP) activity in Arc/Arg3.1 knockout and wild-type mice
      during track running and flanking sleep periods. Locomotor activity, basic firing
      and spatial coding properties of CA1 cells in knockout mice were not different
      from wild-type mice. During active behavior, however, knockout animals showed a
      significantly shifted balance in LFP power, with a relative loss in high
      frequency (beta-2 and gamma) bands compared to low-frequency bands. Moreover,
      during track-running, knockout mice showed a decrease in phase locking of spiking
      activity to LFP oscillations in theta, beta and gamma bands. Sleep architecture
      in knockout mice was not grossly abnormal. Sharp-wave ripples, which have been
      associated with memory consolidation and replay, showed only minor differences in
      dynamics and amplitude. Altogether, these findings suggest that Arc/Arg3.1
      effects on memory formation are not only manifested at the level of molecular
      pathways regulating synaptic plasticity, but also at the systems level. The
      disrupted power balance in theta, beta and gamma rhythmicity and concomitant loss
      of spike-field phase locking may affect memory encoding during initial storage
      and memory consolidation stages.

PMID- 27038744
TI  - Polymer-based metal nano-coated disposable target for matrix-assisted and matrix
      free laser desorption/ionization mass spectrometry.
AB  - The ideal MALDI/LDI mass spectrometry sample target for an axial TOF instrument
      possesses a variety of properties. Primarily, it should be chemically inert to
      the sample, i.e. analyte, matrix and solvents, highly planar across the whole
      target, without any previous chemical contact and provide a uniform surface to
      facilitate reproducible measurements without artifacts from previous sample or
      matrix compounds. This can be hard to achieve with a metal target, which has to
      be extensively cleaned every time after use. Any cleaning step may leave residues
      behind, may change the surface properties due to the type of cleaning method used
      or even cause microscopic scratches over time hence altering matrix
      crystallization behavior. Alternatively, use of disposable targets avoids these
      problems. As each possesses the same surface they therefore have the potential to
      replace the conventional full metal targets so commonly employed. Furthermore,
      low cost single-use targets with high planarity promise an easier compliance with
      GLP guidelines as they alleviate the problem of low reproducibility due to
      inconsistent sample/matrix crystallization and changes to the target surface
      properties. In our tests, polymeric metal nano-coated targets were compared to a
      stainless steel reference. The polymeric metal nano-coated targets exhibited all
      the performance characteristics for a MALDI MS sample support, and even surpassed
      the - in our lab commonly used - reference in some aspects like limit of
      detection. The target exhibits all necessary features such as electrical
      conductivity, vacuum, laser and solvent compatibility.

PMID- 27038745
TI  - High-throughput, high-force probing of DNA-protein interactions with magnetic
      tweezers.
AB  - Recent advances in high-throughput single-molecule magnetic tweezers have paved
      the way for obtaining information on individual molecules as well as ensemble
      averaged behavior in a single assay. Here we describe how to design robust high
      throughput magnetic tweezers assays that specifically require application of high
      forces (>20pN) for prolonged periods of time (>1000s). We elaborate on the
      strengths and limitations of the typical construct types that can be used and
      provide a step-by-step guide towards a high tether yield assay based on two
      examples. Firstly, we discuss a DNA hairpin assay where force-induced strand
      separation triggers a tight interaction between DNA-binding protein Tus and its
      binding site Ter, where forces up to 90pN for hundreds of seconds were required
      to dissociate Tus from Ter. Secondly, we show how the LTag helicase of Simian
      virus 40 unwinds dsDNA, where a load of 36pN optimizes the assay readout. The
      approaches detailed here provide guidelines for the high-throughput, quantitative
      study of a wide range of DNA-protein interactions.

PMID- 27038746
TI  - Simple calibration of TIR field depth using the supercoiling response of DNA.
AB  - The combination of single-molecule fluorescence and nanomanipulation techniques
      into a single experimental platform enables one to carry out correlative analysis
      of the composition and the activity of complex, multicomponent molecular systems.
      Here we describe implementation and calibration of such a combined system
      allowing simultaneous single-molecule force spectroscopy and fluorescence imaging
      of proteins acting on the DNA using magnetic trapping coupled with fluorescence
      excitation based on a Total Internal Reflection (TIR), or evanescent, field. We
      propose a simple and robust in situ method for calibration of the TIR field depth
      against the mechanical properties of nanomanipulated DNA, and which is made
      possible by the fact that the magnetic bead used to trap and nanomanipulate DNA
      and measure its conformation also exhibits autofluorescence in the TIR field.
      Indeed, the fact that the bead size is on the 1-micron scale does not preclude
      sensitive probing of an intensity field which decays exponentially on the
      0.1micron-scale. We demonstrate the usefulness of this approach by mapping out
      TIR field depth as a function of the angle of incidence of the illuminating laser
      at the glass-water interface and showing that one recovers the expected
      theoretical relationship between field depth and angle of incidence.

PMID- 27038747
TI  - Visualizing recombination intermediates with single-stranded DNA curtains.
AB  - Homologous recombination (HR) is a critical cellular process for repairing double
      stranded DNA breaks (DSBs) - a toxic type of DNA lesion that can result in
      chromosomal rearrangements and cancer. During the early stages of HR, members
      from the Rad51/RecA family of recombinases assemble into long filaments on the
      single-stranded DNA overhangs that are present at processed DSBs. These
      nucleoprotein filaments are referred to as presynaptic complexes, and these
      presynaptic complexes must align and pair homologous DNA sequences during HR.
      Traditional ensemble methods cannot easily access the transient and often
      heterogeneous intermediates that are typical of DNA recombination reactions, and
      as a consequence, there remain many open questions with respect to the molecular
      details of this pathway. Novel single-molecule approaches that are capable of
      directly visualizing reaction intermediates in solution and in real time offer
      the potential for new insights into the mechanism of homologous DNA
      recombination. Here we highlight recently developed single stranded DNA curtain
      methods for studying the properties of individual Rad51 presynaptic complexes and
      other related recombination intermediates at the single-molecule level.

PMID- 27038748
TI  - Slow sulfide donor GYY4137 differentiates NG108-15 neuronal cells through
      different intracellular transporters than dbcAMP.
AB  - Cellular differentiation is the process, by which a cell changes from one cell
      type to another, preferentially to the more specialized one. Calcium fluxes play
      an important role in this action. Differentiated NG108-15 or PC12 cells serve as
      models for studying neuronal pathways. NG108-15 cell line is a reliable model of
      cholinergic neuronal cells. These cells differentiate to a neuronal phenotype due
      to the dibutyryl cAMP (dbcAMP) treatment. We have shown that a slow sulfide donor
      - GYY4137 - can also act as a differentiating factor in NG108-15 cell line.
      Calcium is an unavoidable ion required in NG108-15 cell differentiation by both,
      dbcAMP and GYY4137, since cultivation in EGTA completely prevented
      differentiation of these cells. In this work we focused primarily on the role of
      reticular calcium in the process of NG108-15 cell differentiation. We have found
      that dbcAMP and also GYY4137 decreased reticular calcium concentration by
      different mechanisms. GYY4137 caused a rapid decrease in type 2 sarco/endoplasmic
      calcium ATPase (SERCA2) mRNA and protein, which results in lower calcium levels
      in the endoplasmic reticulum compared to the control, untreated group. The dbcAMP
      revealed rapid increase in expression of the type 3 IP3 receptor, which
      participates in a calcium clearance from the endoplasmic reticulum. These results
      point to the important role of reticular calcium in a NG108-15 cell
      differentiation.

PMID- 27038749
TI  - The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation
      and neuroplasticity.
AB  - Insulin-Like Growth Factor 1 (IGF-1) is a phylogenetically ancient neurotrophic
      hormone with crucial roles to play in CNS development and maturation. Recently,
      IGF-1 has been shown to have potent effects on cellular neuroplasticity.
      Neuroplasticty refers to the adaptive changes made by the CNS in the face of
      changing functional demands and is crucial in processes such as learning and
      memory. IGF-1, signaling through its glycoprotein receptor (IGF-1R), and
      canonical signaling pathways such as the PI3K-Akt and Ras-Raf-MAP pathways, has
      potent effects on cellular neuroplasticity in the CNS. In the present review, the
      role of IGF-1 in brain development is reviewed, followed by a detailed discussion
      of the role played by IGF in cellular neuroplasticity in the CNS. Findings from
      models of perturbed and reparative plasticity detailing the role played by IGF-1
      are discussed, followed by the electrophysiological, structural and functional
      evidence supporting this role. Finally, the post-lesion and post-injury roles
      played by IGF-1 are briefly evaluated. We discuss the putative neurobiology
      underlying these changes, reviewing recent evidence and highlighting areas for
      further research.

PMID- 27038751
TI  - beta-Dystroglycan cleavage by matrix metalloproteinase-2/-9 disturbs aquaporin-4
      polarization and influences brain edema in acute cerebral ischemia.
AB  - Dystroglycan (DG) is widely expressed in various tissues, and throughout the
      cerebral microvasculature. It consists of two subunits, alpha-DG and beta-DG, and
      the cleavage of the latter by matrix metalloproteinase (MMP)-2 and -9 underlies a
      number of physiological and pathological processes. However, the involvement of
      MMP-2/-9-mediated beta-DG cleavage in cerebral ischemia remains uncertain. In
      astrocytes, DG is crucial for maintaining the polarization of aquaporin-4 (AQP4),
      which plays a role in the regulation of cytotoxic and vasogenic edema. The
      present study aimed to explore the effects of MMP-2/-9-mediated beta-DG cleavage
      on AQP4 polarization and brain edema in acute cerebral ischemia. A model of
      cerebral ischemia was established via permanent middle cerebral artery occlusion
      (pMCAO) in male C57BL/6 mice. Western blotting, real-time polymerase chain
      reaction (PCR), immunohistochemical staining, immunofluorescent staining,
      electron microscopy, and light microscopy were used. Captopril was applied as a
      selective MMP-2/-9 inhibitor. Recombinant mouse MMP (rmMMP)-2 and -9 were used in
      an in vitro cleavage experiment. The present study demonstrated evidence of beta
      DG cleavage by MMP-2/-9 in pMCAO mouse brains; this cleavage was implicated in
      AQP4 redistribution and brain edema in cerebral ischemia. In addition, captopril
      exacerbated cytotoxic edema and ameliorated vasogenic edema at 24h after pMCAO,
      and alleviated brain edema and neurological deficit at 48h and 72h. In
      conclusion, this study provides novel insight into the effects of MMP-2/-9
      mediated beta-DG cleavage in acute cerebral ischemia. Such findings might
      facilitate the development of a therapeutic strategy for the optimization of MMP
      2/-9 targeted treatment in cerebral ischemia.

PMID- 27038750
TI  - Effects of early and late neonatal bromocriptine treatment on hypothalamic
      neuropeptides, dopaminergic reward system and behavior of adult rats.
AB  - In humans, bromocriptine (BRO) is used as a treatment for many disorders, such as
      prolactinomas, even during pregnancy and lactation. Previously we demonstrated
      that maternal BRO treatment at the end of lactation programs offspring for
      obesity and several endocrine dysfunctions. Here, we studied the long-term
      effects of direct BRO injection in neonatal Wistar rats on their dopaminergic
      pathway, anxiety-like behavior and locomotor activity at adulthood. Male pups
      were either s.c. injected with BRO (0.1MUg/once daily) from postnatal day (PN) 1
      to 10 or from PN11 to 20. Controls were injected with methanol-saline. Body mass,
      food intake, neuropeptides, dopamine pathway parameters, anxiety-like behavior
      and locomotor activity were analyzed. The dopamine pathway was analyzed in the
      ventral tegmental area (VTA), nucleus accumbens (NAc) and dorsal striatum (DS) at
      PN180. PN1-10 BRO-treated animals had normal body mass and adiposity but lower
      food intake and plasma prolactin (PRL). This group had higher POMC in the arcuate
      nucleus (ARC), higher tyrosine hydroxylase (TH) in the VTA, higher dopa
      decarboxylase (DDc), higher D2R and MUu-opioid receptor in the NAc. Concerning
      behavior in elevated plus maze (EPM), BRO-treated animals displayed more anxiety
      like behaviors. PN11-20 BRO-treated showed normal body mass and adiposity but
      higher food intake and plasma PRL. This group had lower POMC in the ARC, lower TH
      in the VTA and lower DAT in the NAc. BRO-treated animals showed less anxiety-like
      behaviors in the EPM. Thus, neonatal BRO injection, depending on the time of
      treatment, leads to different long-term dysfunctions in the dopaminergic reward
      system, food intake behavior and anxiety levels, findings that could be partially
      due to PRL and POMC changes.

PMID- 27038752
TI  - Connexin23 deletion does not affect lens transparency.
AB  - While connexin46 (Cx46) and connexin50 (Cx50) are crucial for maintaining lens
      transparency and growth, the contributions of a more recently identified lens
      fiber connexin, Cx23, are poorly understood. Therefore, we studied the
      consequences of absence of Cx23 in mouse lenses. Cx23-null mice were generated by
      homologous Cre recombination. Cx23 mRNA was abundantly expressed in wild type
      lenses, but not in Cx23-null lenses. The transparency and refractive properties
      of Cx23-null lenses were similar to wild type lenses when examined by darkfield
      microscopy. Neither the focusing ability nor the light scattering was altered in
      the Cx23-null lenses. While both Cx46 and Cx50 localized to appositional fiber
      cell membranes (as in wild type lenses), their levels were consistently (but not
      significantly) decreased in homozygous Cx23-null lenses. These results suggest
      that although Cx23 expression can influence the abundance of the co-expressed
      lens fiber connexins, heterozygous or homozygous expression of a Cx23-null allele
      does not alter lens transparency.

PMID- 27038753
TI  - Preparing neural stem/progenitor cells in PuraMatrix hydrogel for transplantation
      after brain injury in rats: A comparative methodological study.
AB  - Cultivation of neural stem/progenitor cells (NS/PCs) in PuraMatrix (PM) hydrogel
      is an option for stem cell transplantation. The efficacy of a novel method for
      placing adult rat NS/PCs in PM (injection method) was compared to encapsulation
      and surface plating approaches. In addition, the efficacy of injection method for
      transplantation of autologous NS/PCs was studied in a rat model of brain injury.
      NS/PCs were obtained from the subventricular zone (SVZ) and cultivated without
      (control) or with scaffold (three-dimensional cultures; 3D). The effect of
      different approaches on survival, proliferation, and differentiation of NS/PCs
      were investigated. In in vivo study, brain injury was induced 45 days after
      NS/PCs were harvested from the SVZ and phosphate buffered saline, PM, NS/PCs, or
      PM+NS/PCs were injected into the brain lesion. There was an increase in cell
      viability and proliferation after injection and surface plating of NS/PCs
      compared to encapsulation and neural differentiation markers were expressed seven
      days after culturing the cells. Using injection method, transplantation of NS/PCs
      cultured in PM resulted in significant reduction of lesion volume, improvement of
      neurological deficits, and enhancement of surviving cells. In addition, the
      transplanted cells could differentiate in to neurons, astrocytes, or
      oligodendrocytes. Our results indicate that the injection and surface plating
      methods enhanced cell survival and proliferation of NS/PCs and suggest the
      injection method as a promising approach for transplantation of NS/PCs in brain
      injury. 

PMID- 27038754
TI  - Bioluminescence imaging of transplanted human endothelial colony-forming cells in
      an ischemic mouse model.
AB  - Ischemic strokes are devastating events responsible for high mortality and
      morbidity worldwide each year. Endothelial colony-forming cell (ECFC) therapy
      holds promise for stroke treatment; however, grafted ECFCs need to be monitored
      better understand their biological behavior in vivo, so as to evaluate their
      safety and successful delivery. The objectives of this study are to visualize the
      fate of infused human cord blood derived ECFCs via bioluminescence imaging (BLI)
      in an ischemic stroke mouse model and to determine the therapeutic effects of
      ECFC transplantation. ECFCs derived from human umbilical cord blood were infected
      with lentivirus carrying enhanced green fluorescent protein (eGFP) and firefly
      luciferase (Luc2) double fusion reporter gene. Labeled ECFCs were grafted into a
      photothrombotic ischemic stroke mouse model via intra-arterial injection though
      the left cardiac ventricle. The homing of infused cells and functional recovery
      of stroke mice were evaluated using BLI, neurological scoring, and
      immunohistochemistry. Significantly, BLI signals were highest in the brain on day
      1 and decreased steadily until day 14. GFP-positive cells were also found
      surrounding infarct border zones in brain sections using immunohistochemical
      staining, suggesting that ECFCs properly homed to the ischemic brain tissue.
      Using a modified neurological severity score assay and histological analysis of
      brain slices with CD31 immunostaining in brain tissue, double cortin analysis,
      and the TdT-mediated dUTP nick end labeling (TUNEL) assay, we demonstrated
      functional restoration, improved angiogenesis, neurogenesis, and decreased
      apoptosis in ischemic mice after ECFC infusion. Collectively, our data support
      that ECFCs may be a promising therapeutic agent for stroke.

PMID- 27038755
TI  - Mechanisms of neuronal homeostasis: Autophagy in the axon.
AB  - Autophagy is an evolutionarily conserved lysosomal degradation pathway that
      removes damaged organelles and protein aggregates from the cytoplasm. Being post
      mitotic, neurons are particularly vulnerable to the accumulation of proteotoxins
      and are thus heavily dependent on autophagy to maintain homeostasis. In fact, CNS
      specific and neuron-specific loss of autophagy is sufficient to cause
      neurodegeneration in mice. Further, mutations in genes that encode PINK1 and
      Parkin, proteins that selectively remove damaged mitochondria, cause Parkinson's
      disease, linking defective autophagy with neurodegenerative disease in humans.
      This review provides an overview of the mechanisms of autophagy in the axon and
      the role of neuronal autophagy in axonal homeostasis and degeneration. The
      pathway for autophagosome biogenesis and maturation along the axon will be
      discussed as well as several key insights revealing the diverse functions of
      axonal autophagy. Evidence linking altered autophagy with axonal degeneration and
      neuronal death will be presented. Appropriate manipulation of autophagy may lead
      to promising therapeutics for neurodegenerative diseases. This article is part of
      a Special Issue entitled SI:Autophagy.

PMID- 27038756
TI  - The lasting memory enhancements of retrospective attention.
AB  - Behavioral research has shown that spatial cues that orient attention toward task
      relevant items being maintained in visual short-term memory (VSTM) enhance item
      memory accuracy. However, it is unknown if these retrospective attentional cues
      ("retro-cues") enhance memory beyond typical short-term memory delays. It is also
      unknown whether retro-cues affect the spatial information associated with VSTM
      representations. Emerging evidence suggests that processes that affect short-term
      memory maintenance may also affect long-term memory (LTM) but little work has
      investigated the role of attention in LTM. In the current event-related potential
      (ERP) study, we investigated the duration of retrospective attention effects and
      the impact of retrospective attention manipulations on VSTM representations.
      Results revealed that retro-cueing improved both VSTM and LTM memory accuracy and
      that posterior maximal ERPs observed during VSTM maintenance predicted subsequent
      LTM performance. N2pc ERPs associated with attentional selection were attenuated
      by retro-cueing suggesting that retrospective attention may disrupt maintenance
      of spatial configural information in VSTM. Collectively, these findings suggest
      that retrospective attention can alter the structure of memory representations,
      which impacts memory performance beyond short-term memory delays.

PMID- 27038757
TI  - Secretory pathway Ca(2+)-ATPase isoform 1 knockdown promotes Golgi apparatus
      stress injury in a mouse model of focal cerebral ischemia-reperfusion: In vivo
      and in vitro study.
AB  - The present study was designed to investigate the potential role of secretory
      pathway Ca(2+)-ATPase isoform 1(SPCA1) in experimental focal cerebral ischemia
      reperfusion injury. Cerebral ischemia-reperfusion was induced by transient middle
      cerebral artery occlusion (MCAO) for 2h s in Sprague-Dawley rats, and then the
      expression levels of SPAC1 mRNA and protein were determined. Results showed that
      SPCA1 level was transiently increased 1 day after reperfusion in peri-infarction
      area, while markedly increased in infarction core on 3day and 7 day after
      reperfusion. Then a SPCA1 lentivirus was used to achieve knockdown of SPCA1 gene:
      Ca(2+) transporting type 2C, member 1 (ATP2C1) gene. It has been observed that
      SPCA1 knockdown by lentivirus markedly increased cerebral infarction volume in
      vivo. Meanwhile, SPCA1 knockdown also facilitated per-oxidative production,
      including nitric oxide (NO) and 3-nitrotyrosine (3-NT) and decreased the
      expression of total superoxide dismutase (SOD) and manganese superoxide dismutase
      (MnSOD). Moreover, in vitro study showed that SPCA1 knockdown increased hydrogen
      peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and
      elevated caspase3 level in neuro-2a (N2a) cells. In addition, SPCA1 knockdown
      increased H2O2-induced production of nitric oxide and 3-NT dose-dependently, and
      reversed the increased activity of total SOD and MnSOD in neuro-2a cells. In
      conclusion, the present study indicated that SPCA1 could suppress over active
      Golgi apparatus (GA) stress thus attenuate cerebral ischemia-reperfusion injury. 

PMID- 27038758
TI  - Are we ready to sit on a little cloud?

PMID- 27038759
TI  - Aortic arch reconstruction using a Kommerell diverticulum for hypoplastic left
      heart syndrome with a right aortic arch.

PMID- 27038760
TI  - Know your adversary: The type of aortic pathology determines late outcomes after
      thoracic endovascular aortic repair.

PMID- 27038761
TI  - Let's get high.

PMID- 27038762
TI  - Results after spouse donations in living-donor liver transplantation: Does HLA
      matching impact long-term survival?

PMID- 27038763
TI  - Reply to: Independent prognostic factors and unsettled parameters of resected
      primary gastrointestinal stromal tumors.

PMID- 27038764
TI  - Dietary phytic acid prevents fatty liver by reducing expression of hepatic
      lipogenic enzymes and modulates gut microflora in rats fed a high-sucrose diet.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of phytic acid
      (PA) on fatty liver and gut microflora in rats fed a high-sucrose (HSC) diet.
      METHODS: Three groups of rats were fed a high-starch (HSR) diet or an HSC diet
      with or without 1.02% sodium PA for 12 d. We evaluated hepatic weight, total
      lipids, and triacylglycerol (TG) levels, the activities and expression of hepatic
      lipogenic enzymes (glucose-6-phosphate dehydrogenase, malic enzyme 1, and fatty
      acid synthetase), and fecal microflora. RESULTS: The HSC diet significantly
      increased hepatic total lipids and TG levels, and the activities and expression
      of the hepatic lipogenic enzymes compared with the HSR diet. These upregulations
      were clearly suppressed by dietary PA. Consumption of PA elevated the fecal ratio
      of Lactobacillus spp. and depressed the ratio of Clostridium cocoides, and
      suppressed the elevation in the ratio of C. leptum induced by the HSC diet.
      CONCLUSION: This work showed that dietary PA ameliorates sucrose-induced fatty
      liver through reducing the expression of hepatic lipogenesis genes and modulates
      gut microflora in rats.

PMID- 27038765
TI  - Consumption of broccoli sprouts during late gestation and lactation confers
      protection against developmental delay induced by maternal inflammation.
AB  - BACKGROUND: The presence of a fetal inflammatory response is linked to cerebral
      palsy. Unfortunately no preventive therapies are available. In this study, we
      determined whether dietary supplementation with broccoli sprouts (BrSp), a phase
      II enzyme inducer, would be effective in preventing the behavioural and
      pathologic manifestations in a rodent model of inflammation during late
      pregnancy. METHODS: Pregnant Long-Evans rats were administered i.p. Injections of
      saline (100MUl) or lipopolysaccharide (LPS, 200MUg/kg), every 12h on embryonic
      day (E) 19 and 20. In the treatment groups, dams were supplemented with 200mg/day
      of dried BrSp from E14 until postnatal day 21. Pups underwent a series of
      neurodevelopmental reflex tests from postnatal day 3-21 followed by
      neuropathological analyses. RESULTS: Pups born from the LPS group were
      significantly growth restricted (p<0.001) and delayed in hindlimb placing
      (p<0.05), cliff avoidance (p<0.05), and gait (p<0.001) compared to controls. In
      the open field behaviour analyses, LPS pups had an increase in grooming behaviour
      (p<0.05) and a decreased amount of time spent in the center of the box compared
      to controls. Dietary supplementation with BrSp to offspring exposed to LPS had
      increased birth weights (p<0.001), were no longer delayed in acquiring hindlimb
      placing, cliff avoidance, gait, and posture, and groomed less compared to LPS
      alone pups (p<0.01). Histological analyses revealed that LPS pups had reduced
      myelin basic protein compared to controls. CONCLUSIONS: Our data suggest that
      BrSp dietary supplementation during pregnancy may be effective in preventing
      growth restriction and neurodevelopmental delays.

PMID- 27038766
TI  - Real-space path integration is impaired in Alzheimer's disease and mild cognitive
      impairment.
AB  - INTRODUCTION: Path integration (PI) is an important component of spatial
      navigation that integrates self-motion cues to allow the subject to return to a
      starting point. PI depends on the structures affected early in the course of
      Alzheimer's disease (AD) such as the medial temporal lobe and the parietal
      cortex. OBJECTIVES: To assess whether PI is impaired in patients with mild AD and
      amnestic mild cognitive impairment (aMCI) and to investigate the role of the
      hippocampus, entorhinal and inferior parietal cortex in this association.
      METHODS: 27 patients with aMCI, 14 with mild AD and 18 controls completed eight
      trials of Arena Path Integration Task. The task required subjects with a mask
      covering their eyes to follow an enclosed triangle pathway through two previously
      seen places: start-place1-place2-start. Brains were scanned at 1.5T MRI and
      respective volumes and thicknesses were derived using FreeSurfer algorithm.
      RESULTS: Controlling for age, education, gender and Mini-Mental State Examination
      score the aMCI and AD subjects were impaired in PI accuracy on the pathway
      endpoint (p=0.042 and p=0.013) compared to controls. Hippocampal volume and
      thickness of entorhinal and parietal cortices explained separately 36-45% of the
      differences in PI accuracy between controls and aMCI and 28-31% of the
      differences between controls and AD subjects. CONCLUSIONS: PI is affected in aMCI
      and AD, possibly as a function of neurodegeneration in the medial temporal lobe
      structures and the parietal cortex. PI assessment (as a part of spatial
      navigation testing) may be useful for identification of patients with incipient
      AD.

PMID- 27038767
TI  - Catheter Ablation of Recurrent Ventricular Fibrillation: A Literature Review and
      Case Examples.
AB  - Ventricular fibrillation (VF) electrical storm is a serious and life-threatening
      event, and is often triggered by premature ventricular complexes (PVCs). Catheter
      ablation of these PVC triggers have been described in a variety of clinical
      situations, including post-myocardial infarction (MI), patients with structurally
      normal heart, as well as in patients with Brugada Syndrome and Long QT Syndrome.
      We provide a literature review on this topic, using case examples for
      illustration. 

PMID- 27038768
TI  - Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance
      Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.
AB  - PURPOSE: We compared the diagnostic outcomes of magnetic resonance-ultrasound
      fusion and visually targeted biopsy for targeting regions of interest on prostate
      multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Patients
      presenting for prostate biopsy with regions of interest on multiparametric
      magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy.
      For each region of interest 2 visually targeted cores were obtained, followed by
      2 cores using a magnetic resonance-ultrasound fusion device. Our primary end
      point was the difference in the detection of high grade (Gleason 7 or greater)
      and any grade cancer between visually targeted and magnetic resonance-ultrasound
      fusion, investigated using McNemar's method. Secondary end points were the
      difference in detection rate by biopsy location using a logistic regression model
      and the difference in median cancer length using the Wilcoxon signed rank test.
      RESULTS: We identified 396 regions of interest in 286 men. The difference in the
      detection of high grade cancer between magnetic resonance-ultrasound fusion
      biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for
      any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median
      cancer length detected by magnetic resonance-ultrasound fusion and visually
      targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance
      ultrasound fusion biopsy detected 15% more cancers in the transition zone
      (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the
      prostate base (p=0.005). Only 52% of all high grade cancers were detected by both
      techniques. CONCLUSIONS: We found no evidence of a significant difference in the
      detection of high grade or any grade cancer between visually targeted and
      magnetic resonance-ultrasound fusion biopsy. However, the performance of each
      technique varied in specific biopsy locations and the outcomes of both techniques
      were complementary. Combining visually targeted biopsy and magnetic resonance
      ultrasound fusion biopsy may optimize the detection of prostate cancer.

PMID- 27038770
TI  - Low Intensity Extracorporeal Shock Wave Therapy Improves Erectile Function in a
      Model of Type II Diabetes Independently of NO/cGMP Pathway.
AB  - PURPOSE: Erectile dysfunction is highly prevalent in type II diabetes mellitus.
      Low intensity extracorporeal shock wave therapy improves erectile function in
      patients with erectile dysfunction of vasculogenic origin, including diabetes.
      However, its mode of action remains unknown. We investigated the effects of low
      intensity extracorporeal shock wave therapy compared to or combined with
      sildenafil on erectile dysfunction in a type II diabetes mellitus model. Our
      purpose was to test our hypothesis of a mode of action targeting the cavernous
      nitric oxide/cyclic guanosine monophosphate pathway. MATERIALS AND METHODS: GK
      rats, a validated model of type II diabetes mellitus, and age matched Wistar rats
      were treated with low intensity extracorporeal shock wave therapy twice weekly
      for 3 weeks. Treatment was repeated after a 3-week no-treatment interval. The
      penis was stretched and dipped in a specifically designed water-filled cage.
      Shock waves were delivered by a calibrated probe yielding a controlled energy
      flux density (0.09 mJ/mm(2)). The probe was attached to an electrohydraulic unit
      with a focused shock wave source, allowing for accurate extrapolation to humans.
      Following a 4-week washout period erectile function was assessed as well as
      endothelium dependent and independent, and nitrergic relaxations of the corpus
      cavernosum of GK rats. RESULTS: Low intensity extracorporeal shock wave therapy
      significantly improved erectile function in GK rats to the same extent as
      sildenafil. Treatment effects were potentiated when combined with sildenafil.
      Shock wave effects were not associated with improved cavernous endothelium
      dependent or independent, or nitrergic reactivity. CONCLUSIONS: Low intensity
      extracorporeal shock wave therapy improved erectile function in GK rats.
      Unexpectedly, this was not mediated by a nitric oxide/cyclic guanosine
      monophosphate dependent mechanism. Sildenafil increased shock wave efficacy. This
      preclinical paradigm to deliver low intensity extracorporeal shock wave therapy
      to the rat penis should help further exploration of the mode of action of this
      therapy on erectile tissue.

PMID- 27038771
TI  - Preoperative Bladder Urine Culture as a Predictor of Intraoperative Stone Culture
      Results: Clinical Implications and Relationship to Stone Composition.
AB  - PURPOSE: We examine the relationship between urine and stone cultures in a large
      cohort of patients undergoing percutaneous stone removal and compare the findings
      in infectious vs metabolic calculi. MATERIALS AND METHODS: A total of 776
      patients treated with percutaneous nephrolithotomy who had preoperative urine
      cultures and intraoperative stone cultures were included in the study.
      Statistical analysis used chi-square or logistic fit analysis as appropriate.
      RESULTS: Preoperative urine culture was positive in 352 patients (45.4%) and
      stone cultures were positive in 300 patients (38.7%). There were 75 patients
      (9.7%) with negative preoperative cultures who had positive stone cultures, and
      in patients with both cultures positive the organisms differed in 103 (13.3%).
      Gram-positive organisms predominated in preoperative urine and stone cultures.
      CONCLUSIONS: Preoperative urine cultures in patients undergoing percutaneous
      nephrolithotomy are unreliable as there is a discordance with intraoperative
      stone cultures in almost a quarter of cases. There has been a notable shift
      toward gram-positive organisms in this cohort of patients.

PMID- 27038772
TI  - Using eye movements to explore mental representations of space.
AB  - Visual mental imagery is a cognitive experience characterised by the activation
      of the mental representation of an object or scene in the absence of the
      corresponding stimulus. According to the analogical theory, mental
      representations have a pictorial nature that preserves the spatial
      characteristics of the environment that is mentally represented. This cognitive
      experience shares many similarities with the experience of visual perception,
      including eye movements. The mental visualisation of a scene is accompanied by
      eye movements that reflect the spatial content of the mental image, and which can
      mirror the deformations of this mental image with respect to the real image, such
      as asymmetries or size reduction. The present article offers a concise overview
      of the main theories explaining the interactions between eye movements and mental
      representations, with some examples of the studies supporting them. It also aims
      to explain how ocular-tracking could be a useful tool in exploring the dynamics
      of spatial mental representations, especially in pathological situations where
      these representations can be altered, for instance in unilateral spatial neglect.

PMID- 27038769
TI  - Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients
      with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study.
AB  - PURPOSE: These are the final results of the prospective, multicenter, long-term
      (3.5-year) study of the efficacy/safety of onabotulinumtoxinA for overactive
      bladder syndrome. MATERIALS AND METHODS: Patients who completed either of 2, 24
      week phase 3 trials could enter a 3-year extension and continue treatment with
      onabotulinumtoxinA 100 U as needed to control overactive bladder symptoms. Data
      were analyzed by the treatment(s) received (up to 6) and in discrete subgroups
      that received 1, 2, 3, 4, 5 or 6 treatments (to evaluate the consistency of the
      response after repeat treatments in the same patient groups). Assessments
      included the change from baseline in the number of urinary incontinence episodes
      per day and the proportion of patients who reported improvement/great improvement
      in urinary symptoms on the TBS (Treatment Benefit Scale) at week 12 as co-primary
      end points. Other end points were the change from baseline in I-QOL (Incontinence
      Quality of Life), the number of urgency and micturition episodes per day;
      duration of effect; the number of adverse events; and the initiation of
      intermittent catheterization. RESULTS: Consistent mean reductions in urinary
      incontinence were observed following continued onabotulinumtoxinA treatment,
      ranging from -3.1 to -3.8 in the overall population and -2.9 to -4.5 in the
      discrete subgroups. Durable improvements were seen in overactive bladder symptoms
      and quality of life. A high proportion of patients rated their condition as
      improved/greatly improved. The median duration of effect was 7.6 months. The most
      common adverse event was urinary tract infection. The rate of de novo
      catheterization after the first treatment was 4.0% and it ranged from 0.6% to
      1.7% after subsequent treatments. CONCLUSIONS: Long-term onabotulinumtoxinA
      treatment consistently decreased overactive bladder symptoms and improved quality
      of life with no new safety signals.

PMID- 27038773
TI  - A stratified myeloid system, the challenge of understanding macrophage diversity.
AB  - The present issue of 'Seminars in Immunology' addresses the topic of macrophage
      biology, 100 years after the death of Elie Metchnikoff (May 1845-July 1916). As
      foreseen by Metchnikoff, the roles of macrophages in the maintenance of
      homeostasis and immunity against pathogens have become a broad and active area of
      investigation. We now start to realize that the myeloid system includes a
      multiplicity of cell types with diverse developmental origins and functions.
      Therefore, the textbook picture of a plastic and multifunctional macrophage does
      not meet the requirements of our current knowledge anymore. Further development
      toward a quantitative and molecular understanding of myeloid cell biology in vivo
      and their roles in tissue homeostasis and remodeling will benefit from taking
      this complexity into account. A tentative model to help in this pursuit and
      account for myeloid cell and macrophage diversity is discussed below.

PMID- 27038774
TI  - Erratum.

PMID- 27038775
TI  - The genetic relationship between extirpated and contemporary Atlantic salmon
      Salmo salar L. lines from the southern Baltic Sea.
AB  - BACKGROUND: The genetic relationship between original Atlantic salmon populations
      that are now extinct in the southern Baltic Sea and the present-day populations
      has long been controversial. To investigate and clarify this issue, we
      successfully genotyped individuals of the historical populations from the Oder
      and Vistula Rivers using DNA extracted from dried scales with the Atlantic salmon
      single nucleotide polymorphism array. RESULTS: Our results showed a global F ST
      of 0.2515 for all pairs of loci, which indicates a high level of genetic
      differentiation among the groups analyzed in this study. Pairwise F ST values
      were significant for all comparisons and the highest values were found between
      present-day reintroduced Slupia River salmon and extinct Vistula River Atlantic
      salmon. Bayesian analysis of genetic structure revealed the existence of
      substructures in the extirpated Polish populations and three main clades among
      studied stocks. CONCLUSIONS: The historical salmon population from the Oder River
      was genetically closer to present-day salmon from the Neman River than to the
      historical salmon from the Vistula River. Vistula salmon clearly separated from
      all other analyzed salmon stocks. It is likely that the origins of the Atlantic
      salmon population from the Morrum River and the Polish historical native
      populations are different.

PMID- 27038776
TI  - Preconceptional exposure to oral contraceptive pills and the risk of wheeze,
      asthma and rhinitis in children.
AB  - BACKGROUND: The prevalence of maternal oral contraceptive pills (OCP) use and
      that of childhood asthma are high in western countries. The aim of this study is
      to examine the association of OCP use with childhood wheeze and allergic diseases
      in Japan. METHODS: Relevant data were extracted from a hospital based birth
      cohort study named as Tokyo-Children's Health, Illness and Development Study (T
      CHILD) of which questionnaire conducted during pregnancy included maternal
      history and duration of OCP use. To identify wheeze and allergic diseases in the
      children, the questionnaire of the International Study of Asthma and Allergies in
      Childhood (ISAAC) was used. Logistic regression models were applied to estimate
      those association and adjustments were made for maternal history of allergy,
      maternal education level, maternal age at pregnancy, maternal BMI, maternal
      smoking during pregnancy, mode of delivery, gestational age at delivery, daycare
      attendance, number of previous live births, and gender of child. RESULTS: OCP use
      was associated with ever wheeze (adjusted odds ratio [aOR], 1.62; 95% confidence
      interval [CI], 1.10-2.40), current wheeze (aOR, 1.59; 95% CI, 1.01-2.50), ever
      asthma (aOR, 1.65; 95% CI, 1.02-2.65), and ever rhinitis (aOR, 1.90; 95% CI, 1.30
      2.80). Compared with no prior OCP use, using OCP for more than three months
      statistically increased the odds of ever wheeze (P = 0.012), current wheeze (P =
      0.035), and ever rhinitis (P = 0.002). CONCLUSIONS: Our findings suggest that
      maternal OCP use has a role in the development of wheeze, asthma and rhinitis in
      children. Extended use of OCP is likely to increase the risk of wheeze and
      rhinitis.

PMID- 27038777
TI  - Sequence characterization, molecular phylogeny reconstruction and recombination
      analysis of the large RNA of Tomato spotted wilt virus (Tospovirus: Bunyaviridae)
      from the United States.
AB  - BACKGROUND: Tomato spotted wilt virus (TSWV; Tospovirus: Bunyaviridae) has been
      an economically important virus in the USA for over 30 years. However the
      complete sequence of only one TSWV isolate PA01 characterized from pepper in
      Pennsylvania is available. RESULTS: The large (L) RNA of a TSWV WA-USA isolate
      was cloned and sequenced. It consisted of 8914 nucleotides (nt) encoding a single
      open reading frame of 8640 nts in the viral-complementary sense. The ORF
      potentially codes for RNA-dependent RNA polymerase (RdRp) of 330.9 kDa. Two
      untranslated regions of 241 and 33 nucleotides were present at the 5' and 3'
      termini, respectively that shared conserved tospoviral sequences. Phylogenetic
      analysis using nucleotide sequences of the complete L RNA showed that TSWV WA-USA
      isolate clustered with the American and Asian TSWV isolates which formed a
      distinct clade from Euro-Asiatic Tospoviruses. Phylogeny of the amino acid
      sequence of all tospoviral RdRps used in this study showed that all the known
      TSWV isolates including the USA isolate described in this study formed a distinct
      and a close cluster with that of Impateins necrotic spot virus. Multiple sequence
      alignment revealed conserved motifs in the RdRp of TSWV. Recombination analysis
      identified two recombinants including the TSWV WA-USA isolate. Among them, three
      recombination events were detected in the conserved motifs of the RdRp.
      CONCLUSIONS: Sequence analysis and phylogenetic analysis of the L RNA showed
      distinct clustering with selected TSWV isolates reported from elsewhere.
      Conserved motifs in the core polymerase region of the RdRp and recombination
      events were identified.

PMID- 27038778
TI  - The determinants of antimicrobial prescribing among hospital doctors in England:
      a framework to inform tailored stewardship interventions.
AB  - AIM: Little is known about the determinants of antimicrobial prescribing
      behaviour (APB), how they vary between hospital prescribers or the mechanism by
      which interventions are effective. Yet, interventions based on a sound
      theoretical understanding of APB are more likely to be successful in changing
      outcomes. This study sought to quantify the potential determinants of APB among
      hospital doctors in south-west England. METHODS: This multicentre, quantitative
      study employed a closed answer questionnaire to garner hospital doctors' views on
      factors influencing their APB. Underlying constructs within the data were
      identified using exploratory factor analysis and subsequent pairwise comparisons
      assessed for variance between groups of prescribers. RESULTS: The questionnaire
      was completed by 301 doctors across four centres (response rate >= 74%) and three
      key factors were identified: autonomy, guidelines adherence and antibiotic
      awareness. The internal consistency for the questionnaire scale and for each
      factor subscale was good (alpha >= 0.7). Subgroup analysis identified significant
      differences between groups of prescribers: autonomy scores increased with grade
      until at the specialist trainee level (P <= 0.009), foundation doctors scored
      higher for guidelines adherence than consultants (P = 0.004) and specialist
      trainees (P = 0.003) and United Kingdom trained doctors scored higher than those
      trained abroad for antibiotic awareness (P < 0.0005). Scores did not vary
      significantly between doctors from different centres. CONCLUSION: Autonomy,
      guidelines adherence and antibiotic awareness were identified as important
      factors relevant to APB, which vary with experience and training. A theoretical
      framework is offered to facilitate development of more effective, tailored
      interventions to change APBs.

PMID- 27038779
TI  - Type 2 diabetes mellitus induces congenital heart defects in murine embryos by
      increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.
AB  - BACKGROUND: Maternal type 1 and 2 diabetes mellitus are strongly associated with
      high rates of severe structural birth defects, including congenital heart
      defects. Studies in type 1 diabetic embryopathy animal models have demonstrated
      that cellular stress-induced apoptosis mediates the teratogenicity of maternal
      diabetes leading to congenital heart defect formation. However, the mechanisms
      underlying maternal type 2 diabetes mellitus-induced congenital heart defects
      remain largely unknown. OBJECTIVE: We aim to determine whether oxidative stress,
      endoplasmic reticulum stress, and excessive apoptosis are the intracellular
      molecular mechanisms underlying maternal type 2 diabetes mellitus-induced
      congenital heart defects. STUDY DESIGN: A mouse model of maternal type 2 diabetes
      mellitus was established by feeding female mice a high-fat diet (60% fat). After
      15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2
      diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the
      high-fat diet during pregnancy only. Female mice from the high-fat diet group and
      the 2 control groups were mated with male mice that were fed a normal diet. At
      E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides
      and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8,
      and apoptosis. E17.5 embryonic hearts were harvested for the detection of
      congenital heart defect formation using India ink vessel patterning and
      histological examination. RESULTS: Maternal type 2 diabetes mellitus
      significantly induced ventricular septal defects and persistent truncus
      arteriosus in the developing heart, along with increasing oxidative stress
      markers, including superoxide and lipid peroxidation; endoplasmic reticulum
      stress markers, including protein levels of phosphorylated-protein kinase RNA
      like endoplasmic reticulum kinase, phosphorylated-IRE1alpha, phosphorylated
      eIF2alpha, C/EBP homologous protein, and binding immunoglobulin protein;
      endoplasmic reticulum chaperone gene expression; and XBP1 messenger RNA splicing,
      as well as increased cleaved caspase 3 and 8 in embryonic hearts. Furthermore,
      maternal type 2 diabetes mellitus triggered excessive apoptosis in ventricular
      myocardium, endocardial cushion, and outflow tract of the embryonic heart.
      CONCLUSION: Similar to those observations in type 1 diabetic embryopathy,
      maternal type 2 diabetes mellitus causes heart defects in the developing embryo
      manifested with oxidative stress, endoplasmic reticulum stress, and excessive
      apoptosis in heart cells.

PMID- 27038781
TI  - Dentin abrasivity of various desensitizing toothpastes.
AB  - BACKGROUND: The aim of this study was to compare the abrasivity of various
      commercially available toothpastes that claim to reduce dentin hypersensitivity.
      METHODS: Dentin discs were prepared from 70 human extracted molars. The discs
      were etched with lemon juice for 5 min, and one half of the discs were covered
      with aluminum tape. Following this, they were brushed with 6 different
      toothpastes, simulating a total brushing time of 6 months. As a negative control,
      discs were brushed with tap water only. The toothpastes contained pro-arginine
      and calcium carbonate, strontium acetate, stannous fluoride, zinc carbonate and
      hydroxyapatite, new silica, or tetrapotassium pyrophosphate and hydroxyapatite.
      After brushing, the height differences between the control halves and the brushed
      halves were determined with a profilometer and statistically compared using a
      Mann-Whitney U test for independent variables. RESULTS: A significant difference
      (p < 0.001) in height difference between the controls and the toothpaste-treated
      samples was found in all cases, except for the stannous fluoride-containing
      toothpaste (p = 0.583). The highest abrasion was found in the toothpaste
      containing zinc carbonate and hydroxyapatite, and the lowest was found in the
      toothpaste containing pro-arginine and calcium carbonate. CONCLUSIONS:
      Desensitizing toothpastes with different desensitizing ingredients have different
      levels of abrasivity, which may have a negative effect on their desensitizing
      abilities over a long period of time.

PMID- 27038780
TI  - Arrhythmogenic cardiomyopathy.
AB  - Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease clinically
      characterized by life-threatening ventricular arrhythmias and pathologically by
      an acquired and progressive dystrophy of the ventricular myocardium with fibro
      fatty replacement. Due to an estimated prevalence of 1:2000-1:5000, AC is listed
      among rare diseases. A familial background consistent with an autosomal-dominant
      trait of inheritance is present in most of AC patients; recessive variants have
      also been reported, either or not associated with palmoplantar keratoderma and
      woolly hair. AC-causing genes mostly encode major components of the cardiac
      desmosome and up to 50% of AC probands harbor mutations in one of them. Mutations
      in non-desmosomal genes have been also described in a minority of AC patients,
      predisposing to the same or an overlapping disease phenotype. Compound/digenic
      heterozygosity was identified in up to 25% of AC-causing desmosomal gene mutation
      carriers, in part explaining the phenotypic variability. Abnormal trafficking of
      intercellular proteins to the intercalated discs of cardiomyocytes and Wnt/beta
      catenin and Hippo signaling pathways have been implicated in disease
      pathogenesis.AC is a major cause of sudden death in the young and in athletes.
      The clinical picture may include a sub-clinical phase; an overt electrical
      disorder; and right ventricular or biventricular pump failure. Ventricular
      fibrillation can occur at any stage. Genotype-phenotype correlation studies led
      to identify biventricular and dominant left ventricular variants, thus supporting
      the use of the broader term AC.Since there is no "gold standard" to reach the
      diagnosis of AC, multiple categories of diagnostic information have been combined
      and the criteria recently updated, to improve diagnostic sensitivity while
      maintaining specificity. Among diagnostic tools, contrast enhanced cardiac
      magnetic resonance is playing a major role in detecting left dominant forms of
      AC, even preceding morpho-functional abnormalities. The main differential
      diagnoses are idiopathic right ventricular outflow tract tachycardia,
      myocarditis, sarcoidosis, dilated cardiomyopathy, right ventricular infarction,
      congenital heart diseases with right ventricular overload and athlete heart. A
      positive genetic test in the affected AC proband allows early identification of
      asymptomatic carriers by cascade genetic screening of family members. Risk
      stratification remains a major clinical challenge and antiarrhythmic drugs,
      catheter ablation and implantable cardioverter defibrillator are the currently
      available therapeutic tools. Sport disqualification is life-saving, since effort
      is a major trigger not only of electrical instability but also of disease onset
      and progression. We review the current knowledge of this rare cardiomyopathy,
      suggesting a flowchart for primary care clinicians and geneticists.

PMID- 27038782
TI  - Self-compassion, body image, and disordered eating: A review of the literature.
AB  - Self-compassion, treating oneself as a loved friend might, demonstrates
      beneficial associations with body image and eating behaviors. In this systematic
      review, 28 studies supporting the role of self-compassion as a protective factor
      against poor body image and eating pathology are reviewed. Findings across
      various study designs consistently linked self-compassion to lower levels of
      eating pathology, and self-compassion was implicated as a protective factor
      against poor body image and eating pathology, with a few exceptions. These
      findings offer preliminary support that self-compassion may protect against
      eating pathology by: (a) decreasing eating disorder-related outcomes directly;
      (b) preventing initial occurrence of a risk factor of a maladaptive outcome; (c)
      interacting with risk factors to interrupt their deleterious effects; and (d)
      disrupting the mediational chain through which risk factors operate. We conclude
      with suggestions for future research that may inform intervention development,
      including the utilization of research designs that better afford causal
      inference. 

PMID- 27038783
TI  - Vanadium pentoxide nanochains for high-performance electrochemical
      supercapacitors.
AB  - We have synthesized unique hierarchical one dimensional (1D) nanochains of V2O5
      by employing simple hydrothermal method using cetyltrimethylammonium bromide
      (CTAB) as a soft template. The electrochemical performance of resulting V2O5
      electrode materials was evaluated by cyclic voltammetry, galvanostatic charge
      discharge and electrochemical impedance spectroscopy techniques. The V2O5
      nanochains (V2O5-ctab) show maximum specific capacitance of 631 F g(-1) at a
      current density of 0.5 A g(-1) and retain 300 F g(-1) even at high current
      density of 15 A g(-1). In addition the V2O5 nanochains show good cyclic stability
      with 75% capacitance retention after 1200 charge-discharge cycles. The order of
      specific capacitance is commercial bulk-V2O5 (160 F g(-1))<agglomerated V2O5
      particles (395 F g(-1))<V2O5 nanochains (631 F g(-1)). The interconnected
      nanochain-like morphology and high specific surface area are the main factors
      which contribute to higher electrochemical performance to V2O5 nanochains and
      promote facile exchange of Li(+) ions during the charge-discharge processes.

PMID- 27038784
TI  - Azadirachta indica plant-assisted green synthesis of Mn3O4 nanoparticles:
      Excellent thermal catalytic performance and chemical sensing behavior.
AB  - The leaf extract of Azadirachta indica (Neem) plant was utilized as reducing
      agent for the green synthesis of Mn3O4 nanoparticles (NPs). The crystalline
      analysis demonstrated the typical tetragonal hausmannite crystal structure of
      Mn3O4, which confirmed the formation of Mn3O4 NPs without the existence of other
      oxides. Green synthesized Mn3O4 NPs were applied for the catalytic thermal
      decomposition of ammonium perchlorate (AP) and as working electrode for
      fabricating the chemical sensor. The excellent catalytic effect for the thermal
      decomposition of AP was observed by decreasing the decomposition temperature by
      175  degrees C with single decomposing step. The fabricated chemical sensor based
      on green synthesized Mn3O4 NPs displayed high, reliable and reproducible
      sensitivity of ~569.2 MUA mM(-1) cm(-2) with reasonable limit of detection (LOD)
      of ~22.1 MUM and the response time of ~10 s toward the detection of 2-butanone
      chemical. A relatively good linearity in the ranging from ~20 to 160 MUM was
      detected for Mn3O4 NPs electrode based 2-butanone chemical sensor.

PMID- 27038785
TI  - Influence of the separation procedure on the properties of magnetic
      nanoparticles: Gaining in vitro stability and T1-T2 magnetic resonance imaging
      performance.
AB  - Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) coated with
      polyacrylic acid (PAA) were synthesized by a hydrothermal method in gram-scale
      quantity and extensively characterized. Only the nanoparticles subjected to an
      additional centrifugation step showed narrow size distribution, high polymeric
      coverage, and ideal superparamagnetism. In addition to improved physico-chemical
      properties, these nanoparticles feature high stability in vitro as well as dual
      T1-T2 performance as contrast agents (CAs) for magnetic resonance imaging (MRI),
      highlighting the importance of the additional separation step in obtaining
      material with the desired properties. 

PMID- 27038786
TI  - Cost-effectiveness of i-Sleep, a guided online CBT intervention, for patients
      with insomnia in general practice: protocol of a pragmatic randomized controlled
      trial.
AB  - BACKGROUND: Insomnia is a highly prevalent disorder causing clinically
      significant distress and impairment. Furthermore, insomnia is associated with
      high societal and individual costs. Although cognitive behavioural treatment for
      insomnia (CBT-I) is the preferred treatment, it is not used often. Offering CBT-I
      in an online format may increase access. Many studies have shown that online CBT
      for insomnia is effective. However, these studies have all been performed in
      general population samples recruited through media. This protocol article
      presents the design of a study aimed at establishing feasibility, effectiveness
      and cost-effectiveness of a guided online intervention (i-Sleep) for patients
      suffering from insomnia that seek help from their general practitioner as
      compared to care-as-usual. METHODS/DESIGN: In a pragmatic randomized controlled
      trial, adult patients with insomnia disorder recruited through general practices
      are randomized to a 5-session guided online treatment, which is called "i-Sleep",
      or to care-as-usual. Patients in the care-as-usual condition will be offered i
      Sleep 6 months after inclusion. An ancillary clinician, known as the
      psychological well-being practitioner who works in the GP practice (PWP; in
      Dutch: POH-GGZ), will offer online support after every session. Our aim is to
      recruit one hundred and sixty patients. Questionnaires, a sleep diary and wrist
      actigraphy will be administered at baseline, post intervention (at 8 weeks), and
      at 6 months and 12 months follow-up. Effectiveness will be established using
      insomnia severity as the main outcome. Cost-effectiveness and cost-utility (using
      costs per quality adjusted life year (QALY) as outcome) will be conducted from a
      societal perspective. Secondary measures are: sleep diary, daytime consequences,
      fatigue, work and social adjustment, anxiety, alcohol use, depression and quality
      of life. DISCUSSION: The results of this trial will help establish whether online
      CBT-I is (cost-) effective and feasible in general practice as compared to care
      as-usual. If it is, then quality of care might be increased because
      implementation of i-Sleep makes it easier to adhere to insomnia guidelines.
      Strengths and limitations are discussed. TRIAL REGISTRATION: Netherlands Trial
      register NTR 5202 (registered April 17(st) 2015).

PMID- 27038787
TI  - State budget transfers to health insurance funds: extending universal health
      coverage in low- and middle-income countries of the WHO European Region.
AB  - BACKGROUND: Many low-and middle-income countries (LMIC) of the World Health
      Organization (WHO) European Region have introduced social health insurance
      payroll taxes after the political transition in the late 1980s, combined with
      budget transfers to allow for exempting specific population groups from paying
      contributions, such as those outside formal sector work and in particular
      vulnerable groups. This paper assesses the institutional design aspects of such
      financing arrangements and their performance with respect to universal health
      coverage progress in LMIC of the European region. METHODS: The study is based on
      a literature review and review of secondary databases for the performance
      assessment. RESULTS: Such financing arrangements currently exist in 13 LMIC of
      that region, with strong commonalities in institutional design: This includes a
      wide range of different eligible population groups, mostly mandatory membership,
      integrated pools for both the exempted and contributors, and relatively
      comprehensive benefit packages. Performance is more varied. Enrolment rates range
      from about 65 % to above 95 %, and access to care and financial protection has
      improved in several countries. Yet, inequities between income quintiles persist.
      CONCLUSIONS: Budget transfers to health insurance arrangements have helped to
      deepen UHC or maintain achievements with respect to UHC in these European LMICs
      by covering those outside formal sector work, and in particular vulnerable
      population groups. However, challenges remain: a comprehensive benefit package on
      paper is not enough as long as supply side constraints and quality gaps as well
      as informal payments prevail. A key policy question is how to reach those so far
      uncovered.

PMID- 27038788
TI  - Effectiveness of a telemonitoring intensive strategy in early rheumatoid
      arthritis: comparison with the conventional management approach.
AB  - BACKGROUND: The advent of Internet and World Wide Web has created new
      perspectives toward interaction between patients and healthcare professionals.
      Telemonitoring patients with rheumatoid arthritis (RA) is an emerging concept to
      guide the collaborative management treatment and improve outcomes in patients.
      The objective of this study was to investigate whether an intensive treatment
      strategy, according to a telemonitoring protocol, is more effective than
      conventional management strategy in reaching remission and comprehensive disease
      control (CDC) after 1 year in early rheumatoid arthritis (ERA) patients. METHODS:
      Forty-four ERA patients were randomly allocated into two groups: the
      telemonitoring intensive strategy (TIS) group (group 1) or the conventional
      strategy (CS) group (group 2). Three patients refused to participate. In group 1
      (n = 21), a remote monitoring system of disease activity, in combination with
      protocolised treatment adjustments aiming for remission was applied. In group 2
      (n = 20), patients were treated according to daily clinical practice, with
      regular evaluation of disease activity, but without protocolised treatment
      adjustments. A telemedical care called "REmote TElemonitoring for MAnaging
      Rheumatologic Condition and HEaltcare programmes" (RETE-MARCHE), was developed to
      perform the remote monitoring. RESULTS: A higher percentage of patients in the
      TIS group achieved CDAI remission vs patients in the CS group (38.1 % vs 25 % at
      year 1, p <0.01). Time to achieve remission was significantly shorter in the
      group 1 than in the group 2, with a median of 20 weeks vs a median over 36-weeks
      (p <0.001). Concordantly, the patients in group 1 showed a greater improvement (p
      <0.001), compared with group 2 in terms of functional impairment (71.4 % vs 35 %)
      and radiological damage progression (23.8 % vs 10 %), resulting in a greater rate
      of CDC (19.4 % vs 5 %). CONCLUSIONS: According to our results, an intensive
      treatment strategy by telemonitoring leads to more effective disease remission
      and more rapid CDC than treatment according to conventional management strategy
      in ERA. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: ISRCTN13142685 Date of
      registration: March, 17(th) 2016.

PMID- 27038789
TI  - Anticholinergic medication use and falls in postmenopausal women: findings from
      the women's health initiative cohort study.
AB  - BACKGROUND: Results from studies assessing the association between
      anticholinergic use and falls are mixed, and prior studies are limited in their
      ability to control for important potential confounders. Thus, we sought to
      examine the association between anticholinergic medication use, including over
      the-counter medications, and recurrent falls in community-dwelling older women.
      METHODS: We analyzed data from a prospective cohort study of women aged 65 to 79
      years from the Women's Health Initiative Observational Study and Clinical Trials.
      Women were recruited between 1993 and 1998, and analyses included 61,451 women
      with complete information. Medications with moderate or strong anticholinergic
      effects were ascertained directly from drug containers during face-to-face
      interviews. The main outcome measure was recurrent falls (>=2 falls in previous
      year), which was determined from self-report within 1.5 years subsequent to the
      medication assessment. RESULTS: At baseline, 11.3 % were using an anticholinergic
      medication, of which antihistamines (commonly available over-the-counter) were
      the most common medication class (received by 45.2 % of individuals on
      anticholinergic medication). Using multivariable GEE models and controlling for
      potential confounders, the adjusted odds ratio for anticholinergic medication use
      was 1.51 (95 % CI, 1.43-1.60) for recurrent falls. Participants using multiple
      anticholinergic medications had a 100 % increase in likelihood of recurrent falls
      (adjusted odds ratio 2.00, 95 % CI 1.73-2.32). Results were robust to sensitivity
      analysis. CONCLUSIONS: Anticholinergic medication use was associated with
      increased risk for recurrent falls. Our findings reinforce judicious use of
      anticholinergic medications in older women. Public health efforts should
      emphasize educating older women regarding the risk of using over-the-counter
      anticholinergics, such as first-generation antihistamines.

PMID- 27038790
TI  - Clinical efficacy of postoperative adjuvant transcatheter arterial
      chemoembolization on hepatocellular carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical efficacy of
      postoperative adjuvant transcatheter arterial chemoembolization (TACE) on
      hepatocellular carcinoma (HCC). METHODS: Data from 117 patients with HCC who
      underwent hepatectomy between December 2010 and February 2014 were
      retrospectively reviewed. In total, 55 patients underwent surgical resection only
      (group A), and 62 patients underwent surgical resection with adjuvant TACE (group
      B). The perioperative clinical indicators, postoperative sequential treatment,
      and follow-up were compared between the two groups of patients. The Kaplan-Meier
      method was used to compare survival between the groups, and prognostic factors
      were evaluated by a Cox proportional hazard model. RESULTS: The two groups showed
      no significant difference in age, gender, preoperative A-fetoprotein (AFP)
      values, preoperative Child-Pugh score, hepatitis B virus(HBV) DNA levels,
      duration of surgery, hepatectomy technique, albumin values 1-week postoperative,
      postoperative complications, duration of postoperative hospital stay, cirrhosis,
      tumor size, tumor differentiation, tumor encapsulation, satellite nodules, or
      microvascular infiltration. Cox regression analysis revealed that tumor size,
      satellite nodules, and microvascular infiltration were significantly independent
      prognostic factors (P = 0.001, 0.002, and 0.001). Of the 117 patients, the 1-, 2
      , and 3-year disease-free survival rates were 64.5, 50.0, and 41.9%,
      respectively, for group B (62 patients) and 45.5, 36.4, and 30.9%, respectively,
      for group A (55 patients). Although improving trends of disease-free survival
      were observed in the adjuvant TACE group, there was a significant difference in
      postoperative 1-year survival between the two groups (P = 0.04) but no
      significant difference in postoperative 2- and 3-year survival. In patients with
      tumor size >5 cm, the 1-, 2-, and 3-year disease-free survival rates were 41.7,
      25.0, and 12.5%, respectively, for group B and 11.8, 0, and 0%, respectively, for
      group A. There was a significant difference in postoperative 1- and 2-year
      survival between the two groups (P = 0.04 and 0.03, respectively) but no
      significant difference in postoperative 3-year survival. In patients with
      microvascular infiltration, the 1-, 2-, and 3-year disease-free survival rates
      were 42.3, 26.9, and 15.4%, respectively, for group B and 12.5, 4.2, and 0%,
      respectively, for group A. There was a significant difference between the two
      groups (P = 0.02, 0.03, and 0.045, respectively). In patients with satellite
      nodules, the 1-, 2-, and 3-year disease-free survival rates were 50.0, 50, and
      40%, respectively, for group B and 17.6, 0, and 0%, respectively, for group A.
      There was a significant difference between the two groups (P = 0.04, 0.01, and
      0.03, respectively). In patients with tumor size <=5 cm, without satellite
      nodules, or without microvascular infiltration, there was no significant
      difference between the two groups in the 1-, 2-, or 3-year disease-free survival
      rates. Of 117 patients overall, 18 (15.4%) developed hepatitis B virus
      reactivation: 2 (3.6%) patients in group A and 16 (25.8%) patients in group B.
      There was a significant difference between the two groups (P = 0.000). Of these
      patients, one (1.8 %) patient in group A and five (8.1 %) patients in group B
      developed hepatitis due to hepatitis B virus reactivation. There was a
      significant difference between the two groups (P = 0.000). CONCLUSIONS:
      Postoperative adjuvant TACE can improve the 1-year disease-free survival rate of
      HCC patients. Postoperative adjuvant TACE may improve 2- and 3-year disease-free
      survival rates, but no statistical significance was found. For patients with
      tumor size >5 cm, postoperative adjuvant TACE can improve 1- and 2-year disease
      free survival rates, and postoperative adjuvant TACE may improve the 3-year
      disease-free survival rate. For HCC patients with tumor size <=5 cm,
      postoperative adjuvant TACE may improve the 1-, 2-, and 3-year disease-free
      survival rates, but no statistical significance was found. For patients with
      microvascular infiltration or satellite nodules, postoperative adjuvant TACE can
      improve the 1-, 2-, and 3-year disease-free survival rates. For patients without
      microvascular infiltration or without satellite nodules, postoperative adjuvant
      TACE cannot improve 1-, 2-, or 3-year disease-free survival rates. For patients
      with tumor size >5 cm with microvascular infiltration or with satellite nodules,
      postoperative adjuvant TACE was suggested. Hepatitis B virus reactivation can
      occur in patients with postoperative adjuvant TACE; thus, antiviral treatment was
      suggested for these patients.

PMID- 27038791
TI  - Variable use of amiodarone is associated with a greater risk of recurrence of
      atrial fibrillation in the critically ill.
AB  - BACKGROUND: Atrial fibrillation is a common rhythm disturbance in the general
      medical-surgical intensive care unit. Amiodarone is a popular drug in this
      setting but evidence to inform clinical practice remains scarce. We aimed to
      identify whether variation in the clinical use of amiodarone was associated with
      recurrent atrial fibrillation. METHODS: This was a retrospective audit of 177
      critically ill patients who developed new-onset atrial fibrillation after
      admission to a tertiary level medical-surgical trauma intensive care unit.
      Patterns of amiodarone prescription (including dosage schedule and duration) were
      assessed in relation to recurrence of atrial fibrillation during the intensive
      care unit stay. Known recurrence risk factors, such as inotrope administration,
      cardiac disease indices, Charlson Comorbidity Index, magnesium concentrations,
      fluid balance, and potassium concentrations, were also included in adjusted
      analysis using forward stepwise logistic regression modelling. RESULTS: The
      cohort had a median (interquartile range) age of 69 years (60-75), Acute
      Physiology and Chronic Health Evalution II score of 22 (17-28) and Charlson
      Comorbidity Index of 2 (1-4). A bolus dose of amiodarone followed by infusion (P
      = 0.02), in addition to continuing amiodarone infusion through to discharge from
      the intensive care unit (P < 0.001), were associated with less recurrent
      dysrhythmia. Recurrence after successful treatment was associated with ceasing
      amiodarone while an inotrope infusion continued (P < 0.001), and was more common
      in patients with a prior history of congestive cardiac failure (P = 0.04), and a
      diagnosis of systemic inflammatory response syndrome (P = 0.02). CONCLUSIONS:
      Amiodarone should be administered as a bolus dose followed immediately with an
      infusion when treating atrial fibrillation in the medical-surgical intensive care
      unit. Consideration should be given to continuing amiodarone infusions in
      patients on inotropes until they are ceased.

PMID- 27038792
TI  - Do South Indian newborn babies have higher fat percentage for a given birth
      weight?
AB  - BACKGROUND: India is experiencing rapidly escalating epidemics of diabetes and
      cardiovascular disease. High fat percent in Indian adults may have its origins at
      birth (Fetal origin hypothesis). Conflicting evidence from India have shown
      increased or similar fat mass in Indian newborn babies compared to western
      countries. AIM: To compare body composition of term infants with data from
      similar studies in India and developed countries. STUDY DESIGN: Cross-sectional
      study in newborn infants at the antenatal ward of a tertiary care hospital in
      South India. SUBJECTS: 626 mothers and their newborn babies. OUTCOME MEASURES:
      Maternal body weight and height, baby weight, length, head circumference, skin
      folds at three sites. Body fat, arm muscle area and arm muscle index were
      calculated based on known methods. RESULTS: Mean (SD) birth weight of newborn
      babies was 2.80 (0.37) kg and 43% of them were small for gestational age. Birth
      weight was significantly related to subscapular (r=0.445; p<0.001) and triceps
      (r=0.567; p<0.001) skin fold thickness. Mean (CI) Subscapular skin fold thickness
      and total body fat % was 3.81mm (3.74-3.97) and 10.5% (10.2-10.8). Mean total
      body fat % for small for gestational age (SGA) (9.57%) was significantly lower
      than appropriate for gestational age (AGA) babies (11.7%). CONCLUSIONS: The mean
      body fat percent in AGA infants was similar to that of studies reported on term
      infants of developed countries, suggesting that South Indian babies may
      accumulate similar fat mass with increasing birth weight and gestational age.

PMID- 27038793
TI  - Recent discoveries in the molecular genetics of Lynch syndrome.
AB  - Lynch syndrome is the inherited predisposition to cancer caused by a germline
      mutation in a DNA mismatch repair gene. The consequent tumors have a
      characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of
      Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these
      tumors have a substantially greater number of mutations than non-MSI CRCs, and
      that the target mutations driving tumor behavior are also different from what
      occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that
      can create clinical confusion with that disease, including the acquired
      methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with
      Lynch syndrome-associated CRCs have a substantially better prognosis, and there
      is growing evidence that this is due to the generation of immunogenic frameshift
      peptides as a consequence of defective DNA mismatch repair, and an effective
      immune response to the tumor.

PMID- 27038794
TI  - Post-trauma mortality increase at age 60: a cutoff for defining elderly?
AB  - BACKGROUND: There has been an increasing emphasis on identifying elderly trauma
      patients. However, definitions based solely on age vary widely, ranging from age
      55 to 80 years, hampering optimal trauma management for older patients. The goal
      of this study was to develop an objective, data-driven definition for "elderly"
      in trauma care by evaluating mortality risk as a function of age. METHODS: We
      conducted a retrospective analysis of 872,861 adult (>=18 years) patients from
      the National Trauma Data Bank's National Sample Program from 2003 to 2010. The
      primary outcome was risk-adjusted in-hospital mortality determined using
      multivariate logistic regression. Contribution of age to mortality was
      investigated through step-wise regression and percent of R2 attributable to age.
      We searched for straight-line trends in mortality rate at each age using the
      spline function of Statistical Analysis Software. RESULTS: Statistically
      significant increases in mortality rate were noted at ages 37, 60, and 78. Age
      was found to contribute 10% to mortality compared with greater than 80% for
      Glasgow coma scale and injury severity score combined. CONCLUSIONS: Our findings
      suggest using age 60 years as a data-driven definition of "elderly" in trauma.

PMID- 27038796
TI  - Host cell invasion and oral infection by Trypanosoma cruzi strains of genetic
      groups TcI and TcIV from chagasic patients.
AB  - BACKGROUND: Outbreaks of acute Chagas disease by oral infection have been
      reported frequently over the last ten years, with higher incidence in northern
      South America, where Trypanosoma cruzi lineage TcI predominates, being
      responsible for the major cause of resurgent human disease, and a small
      percentage is identified as TcIV. Mechanisms of oral infection and host-cell
      invasion by these parasites are poorly understood. To address that question, we
      analyzed T. cruzi strains isolated from chagasic patients in Venezuela, Guatemala
      and Brazil. METHODS: Trypanosoma cruzi metacyclic trypomastigotes were orally
      inoculated into mice. The mouse stomach collected four days later, as well as the
      stomach and the heart collected 30 days post-infection, were processed for
      histological analysis. Assays to mimic parasite migration through the gastric
      mucus layer were performed by counting the parasites that traversed gastric mucin
      coated transwell filters. For cell invasion assays, human epithelial HeLa cells
      were incubated with metacyclic forms and the number of internalized parasites was
      counted. RESULTS: All TcI and TcIV T. cruzi strains were poorly infective by the
      oral route. Parasites were either undetectable or were detected in small numbers
      in the mouse stomach four days post oral administration. Replicating parasites
      were found in the stomach and/or in the heart 30 days post-infection. As compared
      to TcI lineage, the migration capacity of TcIV parasites through the gastric
      mucin-coated filter was higher but lower than that exhibited by TcVI metacyclic
      forms previously shown to be highly infective by the oral route. Expression of
      pepsin-resistant gp90, the surface molecule that downregulates cell invasion, was
      higher in TcI than in TcIV parasites and, accordingly, the invasion capacity of
      TcIV metacyclic forms was higher. Gp90 molecules spontaneously released by TcI
      metacyclic forms inhibited the parasite entry into host cells. TcI parasites
      exhibited low intracellular replication rate. CONCLUSIONS: Our findings indicate
      that the poor capacity of TcI lineage, and to a lesser degree of TcIV parasites,
      in invading gastric epithelium after oral infection of mice may be associated
      with the inefficiency of metacyclic forms, in particular of TcI parasites, to
      migrate through the gastric mucus layer, to invade target epithelial cells and to
      replicate intracellularly.

PMID- 27038795
TI  - DNA repair genes RAD52 and SRS2, a cell wall synthesis regulator gene SMI1, and
      the membrane sterol synthesis scaffold gene ERG28 are important in efficient
      Agrobacterium-mediated yeast transformation with chromosomal T-DNA.
AB  - BACKGROUND: Plant pathogenic Agrobacterium strains can transfer T-DNA regions of
      their Ti plasmids to a broad range of eukaryotic hosts, including fungi, in
      vitro. In the recent decade, the yeast Saccharomyces cerevisiae is used as a
      model host to reveal important host proteins for the Agrobacterium-mediated
      transformation (AMT). Further investigation is required to understand the
      fundamental mechanism of AMT, including interaction at the cell surface, to
      expand the host range, and to develop new tools. In this study, we screened a
      yeast mutant library for low AMT mutant strains by advantage of a chromosome type
      T-DNA, which transfer is efficient and independent on integration into host
      chromosome. RESULTS: By the mutant screening, we identified four mutant strains
      (srs2Delta, rad52Delta, smi1Delta and erg28Delta), which showed considerably low
      AMT efficiency. Structural analysis of T-DNA product replicons in AMT colonies of
      mutants lacking each of the two DNA repair genes, SRS2 and RAD52, suggested that
      the genes act soon after T-DNA entry for modification of the chromosomal T-DNA to
      stably maintain them as linear replicons and to circularize certain T-DNA
      simultaneously. The cell wall synthesis regulator SMI1 might have a role in the
      cell surface interaction between the donor and recipient cells, but the smi1Delta
      mutant exhibited pleiotropic effect, i.e. low effector protein transport as well
      as low AMT for the chromosomal T-DNA, but relatively high AMT for integrative T
      DNAs. The ergosterol synthesis regulator/enzyme-scaffold gene ERG28 probably
      contributes by sensing a congested environment, because growth of erg28Delta
      strain was unaffected by the presence of donor bacterial cells, while the growth
      of the wild-type and other mutant yeast strains was suppressed by their presence.
      CONCLUSIONS: RAD52 and the DNA helicase/anti-recombinase gene SRS2 are necessary
      to form and maintain artificial chromosomes through the AMT of chromosomal T-DNA.
      A sterol synthesis scaffold gene ERG28 is important in the high-efficiency AMT,
      possibly by avoiding congestion. The involvement of the cell wall synthesis
      regulator SMI1 remains to be elucidated.

PMID- 27038797
TI  - Spondylodiscitis Due to Aspergillus terreus in an Immunocompetent Host: Case
      Report and Literature Review.
AB  - Aspergillus terreus, a saprophytic fungus, is recognized as an emerging pathogen
      responsible for various infections in human beings. However, bone and joint
      involvement is uncommon. We report a rare case of A. terreus spondylodiscitis in
      a 20-year-old male with a past history of recurrent, incompletely treated
      pulmonary tuberculosis. Clinical signs at the time of admission included cough,
      low-grade fever, general weakness and left-sided back pain. Histological
      examination of spinal biopsy samples revealed lesions of necrosis, granulomatous
      inflammation and septate hyphae with acute-angle branching. A. terreus was
      recovered from culture. The patient received antifungal therapy with voriconazole
      plus caspofungin and underwent surgical debridement. Further investigations
      revealed no cause of primary immunodeficiency such as chronic granulomatous
      disease, severe combined immunodeficiency syndrome or disorders of the IL
      12/IFNgamma signaling pathway. Moreover, HIV serological tests resulted negative
      and the patient was not under immunosuppressive therapy. Unfortunately, owing to
      precarity and medication non-adherence, vertebral sequelae occurred. This new
      report emphasizes the need to consider a fungal infection in patients with
      spondylodiscitis, regardless of the immune status. 

PMID- 27038798
TI  - Effects of communication training with the MAAS-Global-D instrument on the
      antibiotic prescribing for respiratory infections in primary care: study protocol
      of a randomised controlled trial.
AB  - BACKGROUND: Primary care physicians account for the majority of antibiotic
      prescribing in ambulatory care in Germany. Respiratory diseases are, regardless
      of effectiveness, often treated with antibiotics. Research has found this use
      without indication to be caused largely by communication problems (e.g.
      expectations on the patient's part or false assumptions about them by the
      physician). The present randomised controlled trial (RCT) study evaluates whether
      communication training for primary care physicians can reduce the antibiotic
      prescribing rate for respiratory tract infections. METHODS/DESIGN: The study
      consists of three groups: group A will receive communication training; group B
      will be given the same, plus additional, access to an evidence-based point-of
      care tool; and group C will function as the control group. The primary endpoint
      is the difference between intervention and control groups regarding the
      antibiotic prescribing rate before and after the intervention assessed through
      routine data. The communication skills are captured with the help of the
      communication instrument MAAS-Global-D, as well as individual videos of physician
      patient consultations recorded by the primary care physicians. These skills will
      also be regarded with respect to the antibiotic prescribing rate. A process
      evaluation using qualitative as well as quantitative methods should provide
      information about barriers and enablers to implementing the communication
      training. DISCUSSION: The trial contributes to an insight into the effectiveness
      of the different components to reduce antibiotic prescribing, which will also be
      supported by an extensive evaluation. Communication training could be an
      effective method of reducing antibiotic prescribing in primary care. TRIAL
      REGISTRATION: DRKS00009566 DATE REGISTRATION: 5 November 2015.

PMID- 27038799
TI  - Genetic characterization of hantaviruses isolated from rodents in the port cities
      of Heilongjiang, China, in 2014.
AB  - BACKGROUND: Hantavirus is a tripartite negative-sense RNA virus. It can infect
      humans through contaminated rodent excreta and causes two types of fatal human
      diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary
      syndrome (HPS). China exhibits the highest HFRS occurrence rate in the world, and
      the Heilongjiang area is one of the most severely infected regions. RESULTS: To
      obtain additional insights into the genetic characteristics of hantaviruses in
      the port cities of the Heilongjiang area in China, a molecular epidemiological
      investigation of hantaviruses isolated from rodents was performed in 2014. A
      total of 649 rodents (11 murine species and 1 shrew species) were caught in 12
      port cities in Heilongjiang. Among these rodents, the most common species was A.
      agrarius, and the second-most common was R. norvegicus. A viral gene PCR assay
      revealed the presence of two specific genotypes of hantavirus, referred to as
      Hantaan virus (HTNV) and Seoul virus (SEOV), and the positive SEOV infection rate
      was higher than that for HTNV. A genetic analysis based on partial M segment
      sequences indicated that all of the isolates belonging to SEOV could be assigned
      to two genetic lineages, whereas the isolate belonging to HTNV could be assigned
      to only one genetic lineage. CONCLUSIONS: These results suggested that HTNV and
      SEOV are circulating in A. agrarius and R. norvegicus in the port cities in the
      area of Heilongjiang, but SEOV may be the dominant common hantavirus.

PMID- 27038800
TI  - Carbamylated vimentin represents a relevant autoantigen in Latin American (Cuban)
      rheumatoid arthritis patients.
AB  - Smoking produces substances that activate proinflammatory, prothrombotic and
      vasoconstrictive mediators via posttranslational carbamylation of proteins. As a
      new consequence of carbamylation, induction of anti-carbamylated autoantibodies
      were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of
      the disease. The overall aim of this study was to characterize the reactivity of
      different isotypes of autoantibodies against carbamylated antigens of vimentin in
      relation to established rheumatoid factor (RF), anti-citrullinated protein
      antibodies (ACPA) and markers of disease activity in a so far largely
      uncharacterized population of Latin American (Cuban) patients with RA. Antigenic
      properties of carbamylated vimentin as well as vimentin peptides were analyzed in
      101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic
      performance was compared with established commercial ELISA rheumatoid factor,
      anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and
      anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV
      IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated
      MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %)
      and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was
      associated with positive IgG antibody reactivity against CCP2 in 75.0 % and
      against MCV in 90 % of patients. Furthermore, IgM antibody response against
      carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due
      to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the
      combination of ACPA with anti-carbVIM IgM provided the best diagnostic
      performance so far achieved in a RA cohort of this ethnic origin. We demonstrate
      a high prevalence of anti-carbVIM antibodies and correlation with smoking in
      Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker
      in ACPA-negative patients and, in combination with ACPA IgG assays, optimizes the
      strategy for autoantibody testing. 

PMID- 27038801
TI  - Full-length genomic characterization and molecular evolution of canine parvovirus
      in China.
AB  - Canine parvovirus type 2 (CPV-2) can cause acute haemorrhagic enteritis in dogs
      and myocarditis in puppies. This disease has become one of the most serious
      infectious diseases of dogs. During 2014 in China, there were many cases of acute
      infectious diarrhoea in dogs. Some faecal samples were negative for the CPV-2
      antigen based on a colloidal gold test strip but were positive based on PCR, and
      a viral strain was isolated from one such sample. The cytopathic effect on
      susceptible cells and the results of the immunoperoxidase monolayer assay, PCR,
      and sequencing indicated that the pathogen was CPV-2. The strain was named CPV-NY
      14, and the full-length genome was sequenced and analysed. A maximum likelihood
      tree was constructed using the full-length genome and all available CPV-2
      genomes. New strains have replaced the original strain in Taiwan and Italy,
      although the CPV-2a strain is still predominant there. However, CPV-2a still
      causes many cases of acute infectious diarrhoea in dogs in China. 

PMID- 27038802
TI  - [Sustainability focus in the health plans of the autonomous communities:
      sustainable development as an opportunity].
AB  - OBJECTIVE: To determine the degree to which the health plans of the autonomous
      communities focus on the usual three dimensions of sustainability: economic,
      social and environmental, both in the general level of discourse and in the
      different areas of intervention. METHOD: A qualitative study was conducted
      through content analysis of a large sample of documents. The specific methodology
      was analysis of symbolic and operational sensitivity in a sample of eleven health
      plans of the Spanish state. RESULTS: Social aspects, such as social determinants
      or vulnerable groups, are receiving increasing attention from the health planner,
      although there is room to strengthen attention to environmental issues and to
      provide specific interventions in economic terms. CONCLUSIONS: The analysis
      demonstrates the incipient state of health plans as strategic planning documents
      that integrate economic, social and environmental aspects and contribute to the
      sustainability of the different health systems of the country.

PMID- 27038803
TI  - Towards equity and sustainability of rural and remote health services access:
      supporting social capital and integrated organisational and professional
      development.
AB  - BACKGROUND: Access to rural health services is compromised in many countries
      including Australia due to workforce shortages. The issues that consequently
      impact on equity of access and sustainability of rural and remote health services
      are complex. DISCUSSION: The purpose of this paper is to describe a number of
      approaches from the literature that could form the basis of a more integrated
      approach to health workforce and rural health service enhancement that can be
      supported by policy. A case study is used to demonstrate how such an approach
      could work. Disjointed health services are common in rural areas due to the
      'tyranny of distance.' Recruitment and retention of health professionals in rural
      areas and access to and sustainability of rural health services is therefore
      compromised. Strategies to address these issues tend to have a narrow focus. An
      integrated approach is needed to enhance rural workforce and health services; one
      that develops, acknowledges and accounts for social capital and social relations
      within the rural community.

PMID- 27038804
TI  - Species-Independent Modeling of High-Frequency Ultrasound Backscatter in Hyaline
      Cartilage.
AB  - Apparent integrated backscatter (AIB) is a common ultrasound parameter used to
      assess cartilage matrix degeneration. However, the specific contributions of
      chondrocytes, proteoglycan and collagen to AIB remain unknown. To reveal these
      relationships, this work examined biopsies and cross sections of human, ovine and
      bovine cartilage with 40-MHz ultrasound biomicroscopy. Site-matched estimates of
      collagen concentration, proteoglycan concentration, collagen orientation and cell
      number density were employed in quasi-least-squares linear regression analyses to
      model AIB. A positive correlation (R(2) = 0.51, p < 10(-4)) between AIB and a
      combination model of cell number density and collagen concentration was obtained
      for collagen orientations approximately perpendicular (>70 degrees ) to the sound
      beam direction. These findings indicate causal relationships between AIB and
      cartilage structural parameters and could aid in more sophisticated future
      interpretations of ultrasound backscatter.

PMID- 27038805
TI  - Nuances in the Management of Older People With Multiple Myeloma.
AB  - Multiple myeloma is a disease of the elderly, with about a third of patients at
      diagnosis older than 75 years of age. Yet, the population of elderly patients is
      heterogeneous: older patients are more likely to have comorbidities and frailties
      complicating both their initial diagnosis and subsequent management, but these
      are not consistent across the group. Furthermore, patients with comorbidities and
      frailty are generally underrepresented in clinical trials. Despite the survival
      of myeloma patients increasing following the introduction of novel agents, older
      patients continue to have worse outcomes with increased treatment-related
      toxicity. Treatment tolerability is not defined by age alone, rather a
      combination of age, physical function, cognitive function, and comorbidities.
      These factors all influence patients' tolerability of treatment and therefore
      treatment efficacy and should also be considered when reviewing the results of
      clinical trials. It is the nuances of determining how these factors interact that
      should influence initial treatment and ongoing management decisions and these
      will be discussed here.

PMID- 27038806
TI  - Successful Conversion From Parenteral Paricalcitol to Pulse Oral Calcitriol for
      the Management of Secondary Hyperparathyroidism in Hemodialysis Patients.
AB  - OBJECTIVE: The management of hyperparathyroidism in hemodialysis patients
      involves the administration of phosphate binders, vitamin D receptor activators,
      and calcimimetics. Intravenous paricalcitol has been preferred over oral
      calcitriol as it may cause less hypercalcemia and hyperphosphatemia. However,
      there is little data looking at the efficacy and tolerability of oral calcitriol
      in the calcimimetic era particularly in a real practice-based experience. The
      University of California, Irvine free-standing dialysis center converted from
      routine intravenous paricalcitol to oral calcitriol due to pharmacy purchasing
      preferences. We report the efficacy, safety, and cost of such a change. SUBJECTS:
      Ninety-three preconversion intravenous paricalcitol and 91 postconversion oral
      calcitriol. INTERVENTION: Conversion to in-center, pulse, oral calcitriol (0.25
      mcg = 1 mcg paricalcitol) 3 times a week from intravenous paricalcitol.
      Additional dose adjustments were made by the nephrologists based on clinical
      indications. MAIN OUTCOME MEASURE: Five-month average serum calcium, phosphorous,
      and intact parathyroid hormone levels and cardiovascular events pretransition and
      posttransition. RESULTS: There were 93 patients on intravenous paricalcitol
      between April 2013 and August 2013, of which 74 converted to oral calcitriol and
      were included in the postconversion group evaluated between October 2013 and
      February 2014. An additional 17 new patients had initiated calcitriol such that
      91 patients were on oral therapy in the postconversion period. Sevelamer use
      increased from 41 (44.1%) patients preconversion to 48 (52.7%) postconversion,
      whereas calcium acetate use significantly dropped from 62 (66.7%) to 46 (50.5%)
      (P = .026). Cinacalcet use dropped slightly from 37 (39.7%) patients
      preconversion to 35 (38.4%) postconversion. Average serum calcium, phosphorus,
      and intact parathyroid hormone levels remained unchanged after conversion.
      Percent of values within Kidney Disease Outcome Quality Initiative guidelines
      were similarly maintained. Estimated vitamin D cost savings were $564 per
      person/year. No increase in the incidence of cardiovascular events was observed.
      CONCLUSIONS: We conclude that in-center distributed pulse oral calcitriol may be
      an effective, safe, and economical treatment option for the management of
      hyperparathyroidism in hemodialysis patients.

PMID- 27038807
TI  - Association of Abdominal Circumference, Body Mass Index, and Inflammation in
      Kidney Transplant Recipients.
AB  - OBJECTIVE: Increased abdominal circumference is a marker of obesity, and it is
      associated with increased mortality in renal transplant recipients. Recent
      findings suggest that increased visceral fat deposition is a modifier of
      inflammation. However, little is known about the association of inflammation with
      abdominal circumference in kidney transplant recipients. DESIGN: Cross-sectional.
      SUBJECT: We collected sociodemographic and clinical parameters, medical and
      transplant history, and laboratory data from 985 prevalent kidney transplant
      recipients. Abdominal circumference, body mass index (BMI), and inflammatory
      markers were measured at baseline. Associations of inflammatory markers with
      abdominal circumference and BMI were examined in unadjusted and adjusted
      regression models. RESULTS: Mean +/- standard deviation age was a 51 +/- 13
      years, 57% were men, and 21% were diabetics. Patients with abdominal
      circumference above the median had higher BMI and were older (mean +/- standard
      deviation: 23.9 +/- 3.6 vs. 30.1 +/- 3.9 kg/m(2), P < .001; and 48 +/- 14 vs. 54
      +/- 11 years, P < .001). Furthermore, patients with higher abdominal
      circumference had higher inflammatory parameters: median (interquartile range) C
      reactive protein (mg/L): 2.3 (3.9) versus 4.1 (6.2), P < .001; and IL-6 (pg/mL):
      1.9 (2.2) versus 2.3 (2.4), P < .001. In multivariable-adjusted linear regression
      models, higher abdominal circumference showed significant linear associations
      with inflammatory markers (standardized regression coefficients (beta) of
      abdominal circumference for lnCRP: betaabdominal circumference = 0.29, P < .001;
      and for lnIL-6: betaabdominal circumference = 0.09, P = .018). Moreover, in
      multivariable-adjusted linear regression models, higher BMI showed significant
      linear associations with inflammatory markers (standardized regression
      coefficients (beta) of BMI for lnCRP: betaBMI = 0.24, P < .001; and for white
      blood cells: betaBMI = 0.07, P = .041). CONCLUSIONS: Abdominal circumference and
      BMI are independently associated with inflammatory markers in prevalent kidney
      transplant recipients.

PMID- 27038808
TI  - A multifaceted role for MOF histone modifying factor in genome maintenance.
AB  - MOF (males absent on the first) was initially identified as a dosage compensation
      factor in Drosophila that acetylates lysine 16 of histone H4 (H4K16ac) and
      increased gene transcription from the single copy male X-chromosome. In humans,
      however, the ortholog of Drosophila MOF has been shown to interact with a range
      of proteins that extend its potential significance well beyond transcription. For
      example, recent results indicate MOF is an upstream regulator of the ATM (ataxia
      telangiectasia mutated) protein, the loss of which is responsible for ataxia
      telangiectasia (AT). ATM is a key regulatory kinase that interacts with and
      phosphorylates multiple substrates that influence critical, cell-cycle control
      and DNA damage repair pathways in addition to other pathways. Thus, directly or
      indirectly, MOF may be involved in a wide range of cellular functions. This
      review will focus on the contribution of MOF to cellular DNA repair and new
      results that are beginning to examine the in vivo physiological role of MOF.

PMID- 27038809
TI  - Macronutrient Content of the Diet: What Do We Know About Energy Balance and
      Weight Maintenance?
AB  - The 2013 AHA/ACC Clinical Guideline for the Management of Overweight and Obesity
      recommends a reduced energy diet for weight loss regardless of the macronutrient
      content. However, diet composition may affect the maintenance of weight loss. In
      general, a healthful dietary pattern with reduced portion sizes, low energy dense
      foods, and physical activity are successful for many. Certain populations, such
      as those with insulin resistance, may find reductions in carbohydrate and higher
      levels of unsaturated fats to be more effective and promote greater adherence. Of
      importance is that metabolic adaptations following weight loss also may impact
      weight loss maintenance and should be considered in the transition from weight
      loss to weight stabilization. Thus, weight loss and weight maintenance strategies
      are both important in an intervention for sustaining long-term behavior change. 

PMID- 27038810
TI  - First observation of Dorylus ant feeding in Budongo chimpanzees supports absence
      of stick-tool culture.
AB  - The use of stick- or probe-tools is a chimpanzee universal, recorded in all long
      term study populations across Africa, except one: Budongo, Uganda. Here, after 25
      years of observation, stick-tool use remains absent under both natural
      circumstances and strong experimental scaffolding. Instead, the chimpanzees
      employ a rich repertoire of leaf-tools for a variety of dietary and hygiene
      tasks. One use of stick-tools in other communities is in feeding on the
      aggressive Dorylus 'army ant' species, consumed by chimpanzees at all long-term
      study sites outside of mid-Western Uganda. Here we report the first observation
      of army-ant feeding in Budongo, in which individuals from the Waibira chimpanzee
      community employed detached leaves to feed on a ground swarm. We describe the
      behaviour and discuss whether or not it can be considered tool use, together with
      its implication for the absence of stick-tool 'culture' in Budongo chimpanzees. 

PMID- 27038811
TI  - Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of
      multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for
      Minpp1 in cellular stress response.
AB  - Inositol polyphosphates represent a group of differentially phosphorylated
      inositol metabolites, many of which are implicated to regulate diverse cellular
      processes such as calcium mobilization, vesicular trafficking, differentiation,
      apoptosis, etc. The metabolic network of these compounds is complex and tightly
      regulated by various kinases and phosphatases present predominantly in the
      cytosol. Multiple inositol polyphosphate phosphatase 1 (Minpp1) is the only known
      endoplasmic reticulum (ER) luminal enzyme that hydrolyzes various inositol
      polyphosphates in vitro as well as in vivo conditions. However, access of the
      Minpp1 to cytosolic substrates has not yet been demonstrated clearly and hence
      its physiological function. In this study, we examined a potential role for
      Minpp1 in ER stress-induced apoptosis. We generated a custom antibody and
      characterized its specificity to study the expression of Minpp1 protein in
      multiple mammalian cells under experimentally induced cellular stress conditions.
      Our results demonstrate a significant increase in the expression of Minpp1 in
      response to a variety of cellular stress conditions. The protein expression was
      corroborated with the expression of its mRNA and enzymatic activity. Further, in
      an attempt to link the role of Minpp1 to apoptotic stress, we studied the effect
      of Minpp1 expression on apoptosis following silencing of the Minpp1 gene by its
      specific siRNA. Our results suggest an attenuation of apoptotic parameters
      following knockdown of Minpp1. Thus, in addition to its known role in inositol
      polyphosphate metabolism, we have identified a novel role for Minpp1 as a stress
      responsive protein. In summary, our results provide, for the first time, a
      probable link between ER stress-induced apoptosis and Minpp1 expression.

PMID- 27038813
TI  - Gambling Motives in a Representative Swedish Sample of Risk Gamblers.
AB  - Motives for gambling have been shown to be associated with gambling involvement,
      and hence important in the understanding of the etiology of problem gambling. The
      aim of this study was to describe differences in gambling motives in different
      subgroups of lifetime risk gamblers, categorized by: age, gender, alcohol- and
      drug habits and type of game preferred, when considering the level of risk
      gambling. A random Swedish sample (n = 19,530) was screened for risk gambling,
      using the Lie/Bet questionnaire. The study sample (n = 257) consisted of the
      respondents screening positive on Lie/Bet and completing a postal questionnaire
      about gambling and motives for gambling (measured with the NODS-PERC and the RGQ
      respectively). When considering the level of risk gambling, motives for gambling
      were not associated with gender, whereas younger persons gambled for the
      challenge more often than did older participants. Card/Casino and Sport gamblers
      played to a greater extent for social and challenge reasons then did Lotto/Bingo
      gamblers. EGM-gamblers played more for coping reasons than did Lotto/Bingo
      gamblers. However, this association turned non-significant when considering the
      level of risk gambling. Moderate risk gamblers played for the challenge and
      coping reasons to a greater extent than low risk gamblers motives for gambling
      differ across subgroups of preferred game and between gamblers with low and
      moderate risk. The level of risk gambling is intertwined with motives for
      gambling and should be considered when examining gambling reasons.

PMID- 27038812
TI  - Loss of p27 expression is associated with MEN1 gene mutations in sporadic
      parathyroid adenomas.
AB  - MEN1 is the main gene responsible for tumorigenesis of syndromic and sporadic
      primary hyperparathyroidism (PHPT). Germline mutations of the CDKN1B/p27Kip gene
      have been associated with multiple endocrine tumors in rats and humans. To
      evaluate the involvement of the CDKN1B gene and its relationship with MEN1 in
      sporadic PHPT, we carried out sequencing and loss of heterozygosity analyses of
      the CDKN1B gene in 147 sporadic parathyroid adenomas. p27 immunohistochemistry
      and genetic screening of the MEN1 gene were performed in 50 cases. Three germline
      CDKN1B variants (c.-80C>T, c.-29_-26delAGAG, c.397C>A) were identified in 3/147
      patients. Reduction of CDKN1B gene transcription rate was demonstrated in vitro
      for the novel c.-80C>T and the c.-29_-26delAGAG variants. Loss of p27 expression
      was detected in the tumor carrying the c.-29_-26delAGAG variant. Two tumors
      carrying the CDKN1B variants also harbored a MEN1 mutation. Fifty-four percent of
      50 CDKN1B mutation-negative tumors had a reduction of p27 nuclear staining.
      Somatic MEN1 mutations, identified in 15/50 samples, significantly segregated in
      tumors negative for nuclear and cytoplasmic p27 staining. The germline nature of
      the CDKN1B mutations suggests that they might predispose to PHPT. The lack of
      somatic CDKN1B mutations in our samples points to a rare involvement in
      parathyroid adenomas, despite the frequent loss of nuclear p27 expression. MEN1
      biallelic inactivation seems to be directly related to down-regulation of p27
      expression through the inhibition of CDKN1B gene transcription.

PMID- 27038814
TI  - Is Fear to Intervene with Problem Gamblers Related to Interveners' Gender and
      Status? A Study with VLT Operators.
AB  - We assess how video lottery terminal (VLT) operators' self-perceive their ability
      to recognize a problem gambler, to what extent they are approached by problem
      gamblers seeking for assistance, how many detections and interventions they
      report, and the reasons they give for not intervening with clients who show signs
      of problem gambling. We also examine how these variables are related to the
      operators' gender and status in the establishment. 177 VLT operators anonymously
      completed a structured questionnaire at the beginning of a responsible gambling
      training class held in different French-speaking Swiss towns. The operators felt
      confident in their ability to detect problem gambling behaviors, were rarely
      approached by problem gamblers seeking assistance, and reported fewer
      interventions compared to the number of detections. This reluctance to intervene
      was mainly attributed to the fear of potential negative reactions from the
      client. Female staff were the most reluctant to intervene and the most fearful of
      potential negative reactions from the client. Responsible gambling training
      programs should include coping strategies for dealing with potential negative
      reactions from clients. Our findings suggest that staff gender and status are two
      individual characteristics that should be taken into account when planning
      responsible gambling trainings.

PMID- 27038815
TI  - Brief Intervention Within Primary Care for At-Risk Gambling: A Pilot Study.
AB  - Studies on interventions for at-risk gambling are scarce. This pilot study is the
      first step in a larger project aimed to develop methods to prevent more serious
      gambling problems. Drawing on experiences from the alcohol field, the brief
      intervention (BI) model was tested in a primary care setting. Primary care
      personnel was trained for 2 days. Patients were screened, and those with signs of
      problematic gambling were offered a return visit to discuss their gambling
      habits. Of the 537 screened, 34 (6.3 %) screened positive for problem gambling.
      Of those, 24 were at-risk gamblers whereof 19 agreed to participate. Six of those
      19 took part in a 1-month follow-up. Important information for the planning of
      upcoming studies was collected from the pilot work. Given that the rate of at
      risk gamblers was elevated in this setting we consider primary care a suitable
      arena for intervention. Staff training and support appeared essential, and
      questionnaires should be selected that are clear and well-presented so staff feel
      secure and comfortable with them. The BI model was found to be most suitable for
      patients already known to the caregiver. The number of participants who were
      willing to take part in the follow-up was low. To ensure power in future studies,
      a much larger number of screened patients is evidently necessary.

PMID- 27038816
TI  - Hierarchy of Gambling Choices: A Framework for Examining EGM Gambling Environment
      Preferences.
AB  - This paper presents the Hierarchy of Gambling Choices (HGC), which is a consumer
      oriented framework for understanding the key environmental and contextual
      features that influence peoples' selections of online and venue-based electronic
      gaming machines (EGMs). The HGC framework proposes that EGM gamblers make choices
      in selection of EGM gambling experiences utilising Tversky's (Psychol Rev
      79(4):281-299, 1972). Elimination-by-Aspects model, and organise their choice in
      a hierarchical manner by virtue of EGMs being an "experience good" (Nelson in J
      Polit Econ 78(2):311-329, 1970). EGM features are divided into three levels: the
      platform-including, online, mobile or land-based; the provider or specific venue
      in which the gambling occurs; and the game or machine characteristics, such as
      graphical themes and bonus features. This framework will contribute to the
      gambling field by providing a manner in which to systematically explore the
      environment surrounding EGM gambling and how it affects behaviour.

PMID- 27038818
TI  - Invasive human brucellosis infection in travelers to and immigrants from the Horn
      of Africa related to the consumption of raw camel milk.
AB  - BACKGROUND: Brucellosis is the commonest zoonosis worldwide and typically results
      from ingestion of unpasteurized goat and sheep milk and cheese. Consumption of
      camel milk is common in the Middle East and the Horn of Africa, but is an
      infrequently reported source of brucellosis. METHODS: We report three immigrant
      patients seen in one hospital system between 2007 and 2013 with brucellosis due
      to the consumption of camel milk. RESULTS: The case patients presented after 3-14
      days of symptoms following travel to countries where Brucella is endemic. All
      three patients were bacteremic. One patient had definite infective endocarditis,
      one had possible endocarditis and one patient presented with acute brucellosis.
      The diagnoses were made expeditiously and appropriate treatment initiated.
      CONCLUSIONS: Knowledge of travel, local customs and immigration patterns are keys
      to early Brucella diagnosis and optimal treatment. Previous reports implicating
      camel milk as the source of Brucella infection have been limited to patients
      living in or traveling to and from the Middle East. This report highlights the
      acquisition of Brucella infection in travelers to and immigrants from the Horn of
      Africa related to the consumption of camel milk.

PMID- 27038817
TI  - Elucidating the triplicated ancestral genome structure of radish based on
      chromosome-level comparison with the Brassica genomes.
AB  - KEYMESSAGE: This study presents a chromosome-scale draft genome sequence of
      radish that is assembled into nine chromosomal pseudomolecules. A comprehensive
      comparative genome analysis with the Brassica genomes provides genomic evidences
      on the evolution of the mesohexaploid radish genome. Radish (Raphanus sativus L.)
      is an agronomically important root vegetable crop and its origin and phylogenetic
      position in the tribe Brassiceae is controversial. Here we present a
      comprehensive analysis of the radish genome based on the chromosome sequences of
      R. sativus cv. WK10039. The radish genome was sequenced and assembled into 426.2
      Mb spanning >98 % of the gene space, of which 344.0 Mb were integrated into nine
      chromosome pseudomolecules. Approximately 36 % of the genome was repetitive
      sequences and 46,514 protein-coding genes were predicted and annotated.
      Comparative mapping of the tPCK-like ancestral genome revealed that the radish
      genome has intermediate characteristics between the Brassica A/C and B genomes in
      the triplicated segments, suggesting an internal origin from the genus Brassica.
      The evolutionary characteristics shared between radish and other Brassica species
      provided genomic evidences that the current form of nine chromosomes in radish
      was rearranged from the chromosomes of hexaploid progenitor. Overall, this study
      provides a chromosome-scale draft genome sequence of radish as well as novel
      insight into evolution of the mesohexaploid genomes in the tribe Brassiceae.

PMID- 27038819
TI  - Probing the structure and dynamics of caveolin-1 in a caveolae-mimicking
      asymmetric lipid bilayer model.
AB  - Caveolin-1 is the principle membrane protein of caveolae and plays an important
      role in various cellular processes. The protein contains two helices (H1 and H2)
      connected by a three-residue break. Although caveolin-1 is assumed to adopt a U
      shaped conformation in the transmembrane domain, with both the N-terminus and C
      terminus exposed to the cytoplasm, the structure and dynamics of caveolin-1 in
      membranes are still unclear. Here, we performed six molecular dynamics
      simulations to characterize the structure and dynamics of caveolin-1 (residues
      D82-S136; Cav182-136) in a caveolae-mimicking asymmetric lipid bilayer. The
      simulations reveal that the structure of the caveolin scaffolding domain of
      caveolin-1 is dynamic, as it could be either fully helical or partly
      unstructured. Cav182-136 inserts into the inner leaflet of the asymmetric lipid
      bilayer with a stable U-shaped conformation and orients almost vertical to the
      bilayer surface. The simulations also provide new insights into the effects of
      caveolin-1 on the morphology of caveolae and the possible interacting site of
      cholesterol on caveolin-1. 

PMID- 27038820
TI  - Re: Meniere's disease: Importance of socioeconomic and environmental factors.

PMID- 27038821
TI  - Radiological challenges in distinguishing keratocystic odontogenic tumor from
      ameloblastoma: an extraordinary occurrence in the same patient.
AB  - OBJECTIVES: The aims of this study are to describe the radiological appearance of
      two common odontogenic lesions (keratocystic odontogenic tumor and ameloblastoma)
      arising in the same patient simultaneously with their radiological differences
      and histological correlates, and to describe challenges in radiological
      diagnosis. DESIGN: Single case report. SETTING: Tertiary referral center.
      PARTICIPANTS: Forty-one year-old African-American male patient. MAIN OUTCOME
      MEASURE: Lesion appearance on computed tomography (CT) scan and pathological
      correlates. RESULTS: A 41year-old African-American male presented with
      asymptomatic right maxillary swelling. A CT scan of the maxillofacial skeleton
      showed and expansile and cystic lesion of the right hemimaxilla with trabecular
      osseous expansion, and a left cystic lesion in the left hemimaxilla expanding
      into the pterygopalatine fossa. Biopsy confirmed the suspected diagnoses of right
      ameloblastoma and left keratocystic odontogenic tumor. CONCLUSION: Although they
      are among the most common odontogenic tumors, the presence of concurrent
      ameloblastoma and KOT is an exceedingly rare occurrence in the same patient. The
      appearance on CT scan may help in distinguishing ameloblastoma from KOT by
      looking at bone expansion and high density areas, although the gold standard
      diagnostic test remains open biopsy.

PMID- 27038822
TI  - Medical therapy of maxillary sinus inflammatory myofibroblastic tumors.
AB  - Inflammatory myofibroblastic tumor (IMT) in the maxillary sinus is a diagnostic
      challenge. As IMT has various names, it has various findings in magnetic
      resonance image. Although destructive pattern in computed tomography and
      hypermetabolism in PET CT suggest malignancy, it is debatable whether it is a
      tumor or inflammatory lesion. Treatment of IMT usually includes surgery. However,
      IMT can be dealt with medical treatment according to histologic type and
      localization. We report a rare case of IMT in the maxillary sinus which is
      controlled by medical therapy. 

PMID- 27038823
TI  - A Step Towards Clinical Translation of Biofabrication.

PMID- 27038824
TI  - Erratum to: Serial passage in ducks of a low-pathogenic avian influenza virus
      isolated from a chicken reveals a high mutation rate in the hemagglutinin that is
      likely due to selection in the host.

PMID- 27038825
TI  - Deep sequencing of banana bract mosaic virus from flowering ginger (Alpinia
      purpurata) and development of an immunocapture RT-LAMP detection assay.
AB  - Banana bract mosaic virus (BBrMV) has never been reported in banana plants in
      Hawaii. In 2010, however, it was detected in a new host, flowering ginger
      (Alpinia purpurata). In this study, we characterize the A. purpurata isolate and
      study its spread in flowering ginger in Hawaii. A laboratory study demonstrated
      that BBrMV could be transmitted from flowering ginger to its natural host,
      banana, therefore raising a serious concern about the potential risk to the
      rapidly growing banana industry of Hawaii. To quickly monitor this virus in the
      field, we developed a robust immunocapture reverse transcription loop-mediated
      isothermal amplification (IC-RT-LAMP) assay. Deep sequencing of the BBrMV isolate
      from A. purpurata revealed a single-stranded RNA virus with a genome of 9,713 nt
      potentially encoding a polyprotein of 3,124 aa, and another predicted protein,
      PIPO, in the +2 reading-frame shift. Most of the functional motifs in the
      Hawaiian isolate were conserved among the genomes of isolates from one found in
      the Philippines and India. However, the A. purpurata isolate had an amino acid
      deletion in the Pl protein that was most similar to the Philippine isolate.
      Phylogenetic analysis of an eastern Pacific subpopulation that included A.
      purpurata was closest in genetic distance to a Southeast Asian subpopulation,
      suggesting frequent gene flow and supporting the hypothesis that the A. purpurata
      isolate arrived in Hawaii from Southeast Asia. 

PMID- 27038826
TI  - A single R36Q mutation in the matrix protein of pigeon paramyxovirus type 1
      reduces virus replication and shedding in pigeons.
AB  - Pigeon paramyxovirus type 1 (PPMV-1) is considered an antigenic and variant of
      avian paramyxovirus type 1 (APMV-1) that has adapted to pigeons as hosts.
      However, how this host-specific adaption of PPMV-1 is related to its biological
      characteristics is unknown. In this study, seven unique amino acids in PPMV-1
      that are not present in other APMV-1 strains (n = 39 versus n = 106) were
      identified. R36 of the M protein was found to be not only a unique amino acid but
      also a positive-selection site. To investigate the role of R36 in host
      adaptation, a recombinant PPMV-1 with R36Q mutation was constructed. Our results
      indicated that the an R36Q mutation significantly attenuates pathogenicity in
      chickens, viral growth in both chicken embryo fibroblasts (CEFs) and pigeon
      embryo fibroblasts (PEFs), and virus replication and shedding in pigeons in
      comparison with the wild-type virus, suggesting that R36 is a key residue that
      evolved during the adaptation of PPMV-1 in pigeons. 

PMID- 27038827
TI  - Detection and sequencing of West Nile virus RNA from human urine and serum
      samples during the 2014 seasonal period.
AB  - West Nile virus, a widely distributed mosquito-borne flavivirus, is responsible
      for numerous animal and human infections in Europe, Africa and the Americas. In
      Hungary, the average number of human infections falls between 10 and 20 cases
      each year. The severity of clinically manifesting infections varies widely from
      the milder form of West Nile fever to West Nile neuroinvasive disease (WNND). In
      routine laboratory diagnosis of human West Nile virus infections, serological
      methods are mainly applied due to the limited duration of viremia. However,
      recent studies suggest that detection of West Nile virus RNA in urine samples may
      be useful as a molecular diagnostic test for these infections. The Hungarian
      National Reference Laboratory for Viral Zoonoses serologically confirmed eleven
      acute human infections during the 2014 seasonal period. In three patients with
      neurological symptoms, viral RNA was detected from both urine and serum
      specimens, albeit for a longer period and in higher copy numbers with urine.
      Phylogenetic analysis of the NS3 genomic region of three strains and the complete
      genome of one selected strain demonstrated that all three patients had lineage-2
      West Nile virus infections. Our findings reaffirm the utility of viral RNA
      detection in urine as a molecular diagnostic procedure for diagnosis of West Nile
      virus infections. 

PMID- 27038828
TI  - Survey of molecular chaperone requirement for the biosynthesis of hamster
      polyomavirus VP1 protein in Saccharomyces cerevisiae.
AB  - A number of viruses utilize molecular chaperones during various stages of their
      life cycle. It has been shown that members of the heat-shock protein 70 (Hsp70)
      chaperone family assist polyomavirus capsids during infection. However, the
      molecular chaperones that assist the formation of recombinant capsid viral
      protein 1 (VP1)-derived virus-like particles (VLPs) in yeast remain unclear. A
      panel of yeast strains with single chaperone gene deletions were used to evaluate
      the chaperones required for biosynthesis of recombinant hamster polyomavirus
      capsid protein VP1. The impact of deletion or mild overexpression of chaperone
      genes was determined in live cells by flow cytometry using enhanced green
      fluorescent protein (EGFP) fused with VP1. Targeted genetic analysis demonstrated
      that VP1-EGFP fusion protein levels were significantly higher in yeast strains in
      which the SSZ1 or ZUO1 genes encoding ribosome-associated complex components were
      deleted. The results confirmed the participation of cytosolic Hsp70 chaperones
      and suggested the potential involvement of the Ydj1 and Caj1 co-chaperones and
      the endoplasmic reticulum chaperones in the biosynthesis of VP1 VLPs in yeast.
      Likewise, the markedly reduced levels of VP1-EGFP in Deltahsc82 and Deltahsp82
      yeast strains indicated that both Hsp70 and Hsp90 chaperones might assist VP1
      VLPs during protein biosynthesis. 

PMID- 27038829
TI  - Erratum to: The carboxy-terminal half of nonstructural protein 3A is not
      essential for foot-and-mouth disease virus replication in cultured cell lines.

PMID- 27038830
TI  - Quantitative trait loci affecting pathogen resistance and ripening of grapevines.
AB  - Grapevines (Vitis vinifera L.) form the basis of viticulture, and are susceptible
      to diseases such as downy mildew (Plasmopara viticola) and powdery mildew
      (Erysiphe necator). Therefore, successful viticulture programs require the use of
      pesticides. Breeding for resistance is the only eco-friendly solution. Marker
      assisted selection is currently widely used for grapevine breeding. Consequently,
      traits of interest must be tagged with molecular markers linked to quantitative
      trait loci (QTL). We herein present our findings regarding genetic mapping and
      QTL analysis of resistance to downy and powdery mildew diseases in the progenies
      of the GF.GA-47-42 ('Bacchus' * 'Seyval') * 'Villard blanc' cross. Simple
      sequence repeats and single nucleotide polymorphisms of 151 individuals were
      analyzed. A map consisting of 543 loci was screened for QTL analyses based on
      phenotypic variations observed in plants grown in the field or under controlled
      conditions. A major QTL for downy mildew resistance was detected on chromosome
      18. For powdery mildew resistance, a QTL was identified on chromosome 15. This
      QTL was replaced by a novel QTL on chromosome 18 in 2003 (abnormally high
      temperatures) and 2004. Subsequently, both QTLs functioned together.
      Additionally, variations in the timing of the onset of veraison, which is a
      crucial step during grape ripening, were studied to identify genomic regions
      affecting this trait. A major QTL was detected on linkage group 16, which was
      supplemented by a minor QTL on linkage group 18. This study provides useful
      information regarding novel QTL-linked markers relevant for the breeding of
      disease-resistant grapevines adapted to current climatic conditions. 

PMID- 27038831
TI  - Traffic-related air pollution and childhood acute leukemia in Oklahoma.
AB  - BACKGROUND: While many studies have evaluated the association between acute
      childhood leukemia and environmental factors, knowledge is limited. Ambient air
      pollution has been classified as a Group 1 carcinogen, but studies have not
      established whether traffic-related air pollution is associated with leukemia.
      The goal of our study was to determine if children with acute leukemia had higher
      odds of exposure to traffic-related air pollution at birth compared to controls.
      METHODS: We conducted a case-control study using the Oklahoma Central Cancer
      Registry to identify cases of acute leukemia in children diagnosed before 20
      years of age between 1997 and 2012 (n=307). Controls were selected from birth
      certificates and matched to cases on week of birth (n=1013). Using a novel
      satellite-based land-use regression model of nitrogen dioxide (NO2) and
      estimating road density based on the 2010 US Census, we evaluated the association
      between traffic-related air pollution and childhood leukemia using conditional
      logistic regression. RESULTS: The odds of exposure to the fourth quartile of NO2
      (11.19-19.89ppb) were similar in cases compared to controls after adjustment for
      maternal education (OR: 1.08, 95% CI: 0.75, 1.55). These estimates were stronger
      among children with acute myeloid leukemia (AML) than acute lymphoid leukemia,
      with a positive association observed among urban children with AML (4th quartile
      odds ratio: 5.25, 95% confidence interval: 1.09, 25.26). While we observed no
      significant association with road density, male cases had an elevated odds of
      exposure to roads at 500m from the birth residence compared to controls (OR:
      1.39, 95% CI: 0.93, 2.10), which was slightly attenuated at 750m. CONCLUSIONS:
      Although we observed no association overall between NO2 or road density, this was
      the first study to observe an elevated odds of exposure to NO2 among children
      with AML compared to controls suggesting further exploration of traffic-related
      air pollution and AML is warranted.

PMID- 27038832
TI  - Exposure to polychlorinated biphenyls and the thyroid gland - examining and
      discussing possible longitudinal health effects in humans.
AB  - BACKGROUND: Many previous studies have dealt with the effect of polychlorinated
      biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One
      problem of these studies has been their use of cross-sectional designs.
      OBJECTIVES: The aim of the current study is to investigate longitudinal effects
      of PCBs on the thyroid gland, focusing on: morphological changes in thyroid
      tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid
      antibodies. METHODS: A total of 122 individuals (Mage=44.7) were examined over a
      period of four years (t(1) until t(4)). Medical history was collected via
      interviews, an ultrasound examination was performed and blood samples were taken
      to determine plasma PCB levels, thyroid stimulating hormone (TSH), free
      triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies
      (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone
      receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect
      models were performed controlling for age and total lipids. RESULTS: There were
      negative correlations between higher chlorinated biphenyls and fT3, cross
      sectionally as well as longitudinally. We also found an interaction effect of
      higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high
      exposure, a decrease in fT4 and an increase in TSHRab level were found over time.
      In regards to the other variables, our findings yielded no clear results in the
      examined time period. CONCLUSION: This is the first study to shows a PCB-related
      effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that
      morphological and antibody findings remain inconsistent and do not allow for
      unambiguous interpretation.

PMID- 27038833
TI  - Dendrochemical assessment of mercury releases from a pond and dredged-sediment
      landfill impacted by a chlor-alkali plant.
AB  - Although current Hg emissions from industrial activities may be accurately
      monitored, evidence of past releases to the atmosphere must rely on one or more
      environmental proxies. We used Hg concentrations in tree cores collected from
      poplars and willows to investigate the historical changes of Hg emissions from a
      dredged sediment landfill and compared them to a nearby control location. Our
      results demonstrated the potential value of using dendrochemistry to record
      historical Hg emissions from past industrial activities.

PMID- 27038834
TI  - Comparison of supramesenteric aortic cross-clamping with supraceliac aortic cross
      clamping for aortic reconstruction.
AB  - OBJECTIVE: Supraceliac aortic cross-clamping (SCXC) is routinely used during open
      aortic reconstruction (OAR) of pararenal aortic disease when suprarenal control
      is not feasible. On occasion, however, aortic control may be obtained at the
      supramesenteric level by supramesenteric cross-clamping (SMXC) between the
      superior mesenteric artery and the celiac axis. The purpose of this study was to
      compare outcomes between patients who had SMXC vs SCXC during OAR for both
      aneurysmal and occlusive diseases. METHODS: A retrospective chart review
      identified 69 patients who underwent elective OAR requiring SMXC (n = 18) or SCXC
      (n = 51). All patients with thoracoabdominal aneurysms and those who had
      inframesenteric (suprarenal and infrarenal) aortic control were excluded.
      Propensity score-based matching was performed to adjust for confounding factors
      in a 1:1 ratio to compare outcomes. Late survival was estimated by Kaplan-Meier
      methods. RESULTS: Propensity score-based matching was performed at a 1:1 ratio;
      18 SMXC cases were matched with 18 SCXC cases. The average age was 66.7 years,
      and men constituted 72%. Baseline characteristics were matched, except for the
      incidence of peripheral vascular occlusive disease (72.2% in the SMXC group vs
      33.3% in the SCXC group; P = .04). A majority (80.6%) of patients underwent OAR
      for aneurysmal disease (72.2% in the SMXC group, 88.9% in the SCXC group).
      Intraoperatively, there were no differences in operative times (325 minutes for
      SMXC vs 298 minutes for SCXC; P = .48), but the SMXC group had a longer renal
      ischemia time (40 minutes vs 28 minutes; P = .03). There were no significant
      differences in intraoperative blood loss (2.4 L vs 1.6 L; P = .2) or blood
      product transfusion requirements (packed red blood cells, 2.2 units vs 1.6 units
      [P = .5]; Cell Saver, 1.3 L vs 0.7 L [P = .09]). Overall complication rates did
      not differ significantly (27.8% for SMXC vs 44.4% for SCXC; P = .24). Thirty-day
      mortality rates did not differ between the two groups (0% for SMXC vs 5.6% for
      SCXC; P = 1). CONCLUSIONS: In this study, there were no differences in early
      morbidity or mortality between SMXC and SCXC during aortic reconstruction. SMXC,
      however, can be performed safely and effectively in properly selected patients. A
      larger, multicenter prospective study would help elucidate the potential
      benefits.

PMID- 27038835
TI  - Comparison of a collagen plug arterial closure device with manual compression
      after endovascular interventions for peripheral artery disease.
AB  - OBJECTIVE: Arterial closure devices (ACDs) seem to be safe and effective to
      obtain hemostasis for cardiac interventions and diagnostic vascular procedures.
      However, only limited evidence is presented on therapeutic interventions in
      patients with peripheral atherosclerotic disease. We compared ischemic and
      hemorrhagic complications of an ACD vs manual compression (MC) after puncture of
      the femoral artery for endovascular lower extremity procedures. METHODS: The
      records of all subsequent endovascular interventions for peripheral artery
      disease performed in a large teaching hospital, from January 2012 to April 2014,
      were retrospectively reviewed. The primary outcome was an ischemic complication
      requiring reintervention. Secondary outcomes were hematoma (needing conservative
      or invasive intervention) and infection (needing intervention or antibiotics).
      Multivariate analysis was performed to identify predictors for any complication.
      RESULTS: The Angio-Seal (St. Jude Medical, Minnetonka, Minn) closure device was
      used in 244 of 463 endovascular interventions (54%). Five patients (2%) who
      received an ACD needed emergency surgery for ischemic complications vs none in
      the MC group (P = .06). Hematomas occurred in 22 patients (9%) after ACD vs in
      six (3%) after MC (adjusted odds ratio [OR], 3.4; 95% confidence interval [CI],
      1.4-8.9; P = .015). There were no infections in either group. ACD (OR, 3.8; 95%
      CI, 1.5-9.7) and current smoking (OR, 2.6; 95% CI, 1.01-6.7) were independent
      predictors for any complication. CONCLUSIONS: This study demonstrates that ACD
      use in patients with peripheral artery disease can lead to serious adverse events
      resulting in increased morbidity. Therefore, the potential benefits of an ACD
      over MC should be carefully weighed.

PMID- 27038836
TI  - Temporary inferior vena cava filter indications, retrieval rates, and follow-up
      management at a multicenter tertiary care institution.
AB  - OBJECTIVE: The aim of this study was to investigate the practice pattern of
      inferior vena cava (IVC) filters and to determine factors predictive of filter
      retrievals at a multicenter, tertiary care institution. METHODS: A retrospective
      review of all IVC filter procedures performed between January 2001 and July 2013
      was conducted. Data collected included demographics, venous thromboembolism risk
      factors, medical comorbidities, insertional and retrieval characteristics,
      referring services, complications, discharge, and follow-up management. RESULTS:
      During the study period, 1123 IVC filter procedures were performed; 69% (n = 810)
      were insertions and 31% (n = 313) were retrievals. Of the patients receiving
      filters, the average age was 61.4 years, and 53.3% were male. Overall, 408
      filters (51.5%) were placed with absolute indications, 214 (27.0%) for relative
      indications, 138 (17.4%) prophylactically, and 32 (4.0%) for reasons outside the
      established guidelines. Of the 663 retrievable filters, successful removal rate
      was 41.6% (n = 276); the mean time to first retrieval attempt was 76.4 days
      (standard deviation = 110.5). Documentation of the filter was present in 342
      (43.1%) discharge summaries, and outlined instructions for filter management were
      seen in 129 (16.3%) cases. Significant predictors of filter removal were
      thrombosis follow-up (odds ratio [OR], 6.7; P < .01) and the ordering service as
      filters ordered by medical specialties were less likely to be retrieved than
      filters ordered by surgical specialties (OR, 0.53; P = .04). Compared with
      discharge summaries without filter management instructions, those with plans had
      higher filter retrieval rates (OR, 3.74; P < .00). Filter-related complications
      was observed in 57 patients. CONCLUSIONS: Given the established complications
      relating to long indwelling times and recent Food and Drug Administration
      guidelines, a multidisciplinary and systematic follow-up protocol needs to be
      implemented to optimize filter retrieval rates and to ensure exemplary quality of
      care.

PMID- 27038837
TI  - Outcomes of patients with type I endoleak at completion of endovascular abdominal
      aneurysm repair.
AB  - BACKGROUND: Type I endoleak (TIE) during endovascular aneurysm repair (EVAR) is
      usually identified and treated intraoperatively. We evaluated the outcomes of
      patients who, despite possible treatment, had TIE at completion of EVAR. METHODS:
      We examined consecutive EVAR for nonruptured abdominal aortic aneurysm (AAA)
      within the Vascular Study Group of New England database (2003-2012) and compared
      the outcomes of patients who had TIE at completion with those who did not.
      Outcomes included perioperative death, cardiac complication, reoperation, and 1
      year mortality. Multivariable logistic regression was used to determine factors
      associated with perioperative mortality, as well as factors associated with TIE.
      Anatomic factors associated with TIE were not evaluated because of the
      limitations of the Vascular Study Group of New England database. RESULTS: Among
      the 2402 EVARs for nonruptured AAA in the Vascular Study Group of New England
      sample, 93% (n = 2235) were performed electively and 7% had (n = 167) symptomatic
      AAA. Eighty patients (3.3%) had TIE at completion of surgery. Patients with TIE
      were older (77.9 vs 73.9 years; P < .001), had higher female preponderance (34%
      vs 20%; P = .004), larger endograft main body diameter (28.8 vs 27.2 mm; P <
      .001), and more unplanned graft extension (32% vs 10%; P < .001) than those
      without TIE. At 1-year follow-up, 90% of patients who had TIE at the completion
      of their EVAR had resolution of TIE without further need for endovascular
      intervention or open conversion type I endoleak at the completion of surgery was
      associated with increased in-hospital mortality (5% vs 0.6%; P = .002) and
      cardiac dysrhythmia (8.8% vs 3.2%; P = .02). In multivariable analysis, TIE was
      independently associated with increased odds of in-hospital mortality (odds ratio
      [OR], 4.4; 95% confidence interval [CI], 1.2-16.4; P = .03). Multivariable
      analysis revealed the following factors to be independently predictive of TIE:
      female gender (OR, 2.2, 95% CI, 1.3-3.7; P = .002), patients older than 70 years
      of age (OR, 2.0; 95% CI, 1.1-3.8; P = .02), those with main body graft diameter
      >30 mm (OR, 2.6; 95% CI, 1.6-4.3; P < .001), and those undergoing unplanned graft
      extension (OR, 4.6; 95% CI, 2.7-7.7; P < .001). CONCLUSIONS: TIE occurred in 3%
      of patients at completion of EVAR with more than 90% resolved spontaneously at 1
      year follow-up. It is associated with increased risk of in-hospital mortality and
      cardiac complication. Additional investigation is needed to further define
      anatomic factors associated with TIE and to improve perioperative outcomes of
      these at-risk patients.

PMID- 27038838
TI  - Drivers of readmissions in vascular surgery patients.
AB  - OBJECTIVE: Postoperative readmissions are frequent in vascular surgery patients,
      but it is not clear which factors are the main drivers of readmissions.
      Specifically, the relative contributions of patient comorbidities vs those of
      operative factors and postoperative complications are unknown. We sought to study
      the multiple potential drivers of readmission and to create a model for
      predicting the risk of readmission in vascular patients. METHODS: The 2012-2013
      American College of Surgeons National Surgical Quality Improvement Program data
      set was queried for unplanned readmissions in 86,238 vascular patients.
      Multivariable forward selection logistic regression analysis was used to model
      the relative contributions of patient comorbidities, operative factors, and
      postoperative complications for readmission. RESULTS: The unplanned readmission
      rate was 9.3%. The preoperative model based on patient demographics and
      comorbidities predicted readmission risk with a low C index of .67; the top five
      predictors of readmission were American Society of Anesthesiologists class,
      preoperative open wound, inpatient operation, dialysis dependence, and diabetes
      mellitus. The postoperative model using operative factors and postoperative
      complications predicted readmission risk better (C index, .78); postoperative
      complications were the most significant predictor of readmission, overpowering
      patient comorbidities. Importantly, postoperative complications identified before
      discharge from the hospital were not a strong predictor of readmission as the
      model using predischarge postoperative complications had a similar C index to our
      preoperative model (.68). However, the inclusion of complications identified
      after discharge from the hospital appreciably improved the predictive power of
      the model (C index, .78). The top five predictors of readmission in the final
      model based on patient comorbidities and postoperative complications were
      postdischarge deep space infection, superficial surgical site infection,
      pneumonia, myocardial infection, and sepsis. CONCLUSIONS: Readmissions in
      vascular surgery patients are mainly driven by postoperative complications
      identified after discharge. Thus, efforts to reduce vascular readmissions
      focusing on inpatient hospital data may prove ineffective. Our study suggests
      that interventions to reduce vascular readmissions should focus on prompt
      identification of modifiable postdischarge complications.

PMID- 27038839
TI  - ERP evidence for on-line syntactic computations in 2-year-olds.
AB  - Syntax allows human beings to build an infinite number of sentences from a finite
      number of words. How this unique, productive power of human language unfolds over
      the course of language development is still hotly debated. When they listen to
      sentences comprising newly-learned words, do children generalize from their
      knowledge of the legal combinations of word categories or do they instead rely on
      strings of words stored in memory to detect syntactic errors? Using novel words
      taught in the lab, we recorded Evoked Response Potentials (ERPs) in two-year-olds
      and adults listening to grammatical and ungrammatical sentences containing
      syntactic contexts that had not been used during training. In toddlers, the
      ungrammatical use of words, even when they have been just learned, induced an
      early left anterior negativity (surfacing 100-400ms after target word onset)
      followed by a late posterior positivity (surfacing 700-900ms after target word
      onset) that was not observed in grammatical sentences. This late effect was
      remarkably similar to the P600 displayed by adults, suggesting that toddlers and
      adults perform similar syntactic computations. Our results thus show that
      toddlers build on-line expectations regarding the syntactic category of upcoming
      words in a sentence.

PMID- 27038841
TI  - "Chain of Beads" Appearance of the Superior Mesenteric Artery.

PMID- 27038840
TI  - Basic emotion processing and the adolescent brain: Task demands, analytic
      approaches, and trajectories of changes.
AB  - Early neuroimaging studies suggested that adolescents show initial development in
      brain regions linked with emotional reactivity, but slower development in brain
      structures linked with emotion regulation. However, the increased sophistication
      of adolescent brain research has made this picture more complex. This review
      examines functional neuroimaging studies that test for differences in basic
      emotion processing (reactivity and regulation) between adolescents and either
      children or adults. We delineated different emotional processing demands across
      the experimental paradigms in the reviewed studies to synthesize the diverse
      results. The methods for assessing change (i.e., analytical approach) and cohort
      characteristics (e.g., age range) were also explored as potential factors
      influencing study results. Few unifying dimensions were found to successfully
      distill the results of the reviewed studies. However, this review highlights the
      potential impact of subtle methodological and analytic differences between
      studies, need for standardized and theory-driven experimental paradigms, and
      necessity of analytic approaches that are can adequately test the trajectories of
      developmental change that have recently been proposed. Recommendations for future
      research highlight connectivity analyses and non-linear developmental
      trajectories, which appear to be promising approaches for measuring change across
      adolescence. Recommendations are made for evaluating gender and biological
      markers of development beyond chronological age.

PMID- 27038842
TI  - CD103 defines intraepithelial CD8+ PD1+ tumour-infiltrating lymphocytes of
      prognostic significance in endometrial adenocarcinoma.
AB  - INTRODUCTION: Intraepithelial CD8+ tumour-infiltrating T-lymphocytes (TIL) are
      associated with a prolonged survival in endometrial cancer (EC). By contrast,
      stromal infiltration of CD8+ TIL does not confer prognostic benefit. A single
      marker to discriminate these populations would therefore be of interest for rapid
      assessment of the tumour immune contexture, ex vivo analysis of intraepithelial
      and stromal T-cells on a functional level and/or adoptive T-cell transfer. Here
      we determined whether CD103, the alphaE subunit of the alphaEbeta7integrin, can
      be used to specifically discriminate the epithelial and stromal CD8+ TIL
      populations in EC. METHODS: CD103+ TIL were quantified in a cohort of 305 EC
      patients by immunohistochemistry. Localization of CD103+ cells and co-expression
      of CD103 with CD3, CD8, CD16 and FoxP3 were assessed by immunofluorescence.
      Further phenotyping of CD103+ cells was performed by flow cytometry on primary
      endometrial tumour digests. RESULTS: CD8+CD103+ cells were preferentially located
      in endometrial tumour epithelium, whereas CD8+CD103- cells were located in
      stroma. CD103+ lymphocytes were predominantly CD3+CD8+ T-cells and expressed PD1.
      The presence of a high CD103+ cell infiltration was associated with an improved
      prognosis in patients with endometrial adenocarcinoma (p = 0.035). Moreover, this
      beneficial effect was particularly evident in high-risk adenocarcinoma patients
      (p = 0.031). CONCLUSIONS: Because of the restricted expression on intraepithelial
      CD8+ T-cells, CD103 may be a suitable biomarker for rapid assessment of immune
      infiltration of epithelial cancers. Furthermore, this intraepithelial tumour
      reactive subset might be an interesting T-cell subset for adoptive T-cell
      transfer and/or target for checkpoint inhibition therapy.

PMID- 27038843
TI  - Antibacterial activity of Syzygium aromaticum seed: Studies on oxidative stress
      biomarkers and membrane permeability.
AB  - Oxidative stress and membrane permeability as mode of antibacterial activity of
      aqueous extract of Syzygium aromaticum seeds against Escherichia coli,
      Pseudomonas aeruginosa and Staphylococcus aureus was investigated. The
      concentration of phytochemical constituents of Syzygium aromaticum was determined
      using gas chromatography. Syzygium aromaticum seeds contain eugenol acetate >
      beta-carophyllene > eugenin > eugenol > methyl salicylate > beta-humulene >
      rhamnatin > fernesol > alpha-copeane > beta-ylangene > kaempferol > cinnamic acid
      > oleanolic acid > benzaldehyde > alpha-humulene > vanillin > alpha-cubebene >
      carvicol > benzoic acid. Syzygium aromaticum showed antimicrobial activity with
      minimum inhibitory concentration (MIC) and minimum bactericidal concentration
      (MBC) values as 0.06 and 0.10 mg/mL respectively. Time kill susceptibility by
      Syzygium aromaticum at MBC values showed significant decrease in the optical
      density and colony-forming unit (CFU) of Escherichia coli, Pseudomonas aeruginosa
      and Staphylococcus aureus. Superoxide anion radical content of the bacterial
      cells increased significantly following exposure to the extract. In a similar
      vein, superoxide dismutase and catalase activities increased significantly, while
      the level of reduced glutathione reduced, malondialdehyde increased significantly
      in bacterial cells exposed to the extract. The extract at MBC also enhanced the
      leakage of 260 nm absorbing materials and outer membrane permeability. It is
      evident from the data generated from this study that aqueous extract of Syzygium
      aromaticum seeds enhanced membrane permeability and oxidative stress in
      Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. 

PMID- 27038844
TI  - The role of regulator Eha in Edwardsiella tarda pathogenesis and virulence gene
      transcription.
AB  - Edwardsiella tarda is a pathogen with a broad host range that infects both
      animals and humans. Eha is a new transcriptional regulator identified in ET13,
      which is involved in the bacterial hemolytic activity. This study explored the
      effect of the Eha in the pathogenesis of E. tarda and the transcriptional
      regulation of the bacterial virulence genes (eseC, fliC, pagC and fimA). Our
      results found that the virulence of the eha mutant was 2.5-fold less than the one
      of its wild ET13 by LD50 in a murine model of i.p. infection, and the bacterial
      loads of the mutant displayed a different profile from the one of the wild
      strain. Most significantly, the mice infected with the mutant have greatly
      reduced acute inflammation in the liver, spleen and kidney compared to the ones
      infected with the wild. We further demonstrated that eseC, fliC and pagC were
      regulated directly by the Eha with qRT-PCR and beta-Galactosidase assay, but fimA
      wasn't done. The promoter regions of the genes modulated and the cly gene
      reported before had been found to contain a common conserved motif by using
      software. In addition, we found that the wild strain was more toxic to RAW264.7
      macrophages, and induced less the host cell apoptotic responses than the eha
      mutant did. Altogether, these data suggested that the Eha was required for the
      bacterial infection and the transcriptive regulation of the important virulence
      genes of E. tarda. 

PMID- 27038845
TI  - A case of brugada syndrome presenting with ventricular fibrillation storm and
      prominent early repolarization.
AB  - A 21-year-old man developed ventricular fibrillation (VF) while drinking alcohol
      and was admitted to our hospital. An electrocardiogram (ECG) on admission
      revealed remarkably prominent slurs on the terminal part of QRS complexes in the
      left precordial leads and a coved type ST elevation at higher intercostal spaces.
      After hypothermia therapy, he underwent implantation of an implantable
      cardioverter-defibrillator (ICD). Standard twelve-lead follow-up ECGs revealed
      early repolarization pattern and an intermittent coved type ST elevation. When
      the coved type ST elevation appeared, the early repolarization pattern in the
      inferior and left precordial leads was attenuated. Prominent early repolarization
      pattern was the most likely trigger of the VF storm in this Brugada patient.

PMID- 27038846
TI  - Sinusoidal obstruction syndrome.
AB  - Sinusoidal obstruction syndrome (SOS) is characterized by damage to small hepatic
      vessels affecting particularly sinusoidal endothelium. Damaged sinusoids can be
      associated with a partial or complete occlusion of small hepatic veins, hence the
      previous denomination of hepatic veno-occlusive disease (VOD). Exposure to
      certain exogenous toxins appears to be specific to this condition and is
      frequently included in its definition. Typical histopathological features of SOS
      in a liver biopsy specimen are presented in the text. The purpose of this article
      is to provide an overview on the different entities corresponding to this general
      definition. Such entities include: (i) liver disease related to pyrrolizidine
      alcaloids; (ii) liver injury related to conditioning for hematopoietic stem cell
      transplantation; (iii) vascular liver disease occurring in patients treated with
      chemotherapy for liver metastasis of colorectal cancer; and (iv) other liver
      diseases related to toxic agents. 

PMID- 27038847
TI  - DPP-4 inhibitors and cardiovascular disease in type 2 diabetes mellitus.
      Expectations, observations and perspectives.
AB  - AIMS: Cardiovascular disease (CVD) is the greatest burden of type 2 diabetes
      mellitus (T2DM) in terms of morbility, mortality and costs for individuals and
      societies. Therefore, its prevention is a major goal in diabetes care. Optimal
      treatment of hyperglycemia is certainly instrumental to CVD prevention. Optimal
      treatment means both establishing the most appropriate glycemic target for the
      given individual and selecting the medication(s) with the most favourable
      benefit/safety ratio. CVD safety, if not a clear CVD benefit, is certainly
      required for all antidiabetic agents. Dipeptidyl-peptidase-4 (DPP-4) inhibitors
      are among the classes of antidiabetic agents most recently made available for
      diabetes care. A major question to be addressed is the effect of these compounds
      on CVD. Expectations were high for their mechanism of action, which targets also
      post-prandial glucose and minimize hypoglycemia risk, thereby providing a sort of
      global glucose control, and for some potentially beneficial extra-glycemic
      effects. This article reviews the existing literature on this issue. DATA
      SYNTHESIS: Data published so far document that DPP-4 inhibitors have a wide
      spectrum of glycemic and extra-glycemic effects potentially reducing the risk of
      CVD as well as favourable effects on intermediate or surrogate CVD endpoints.
      These data heralded a better CVD outcome. Accordingly, pooling CVD safety data
      from phase 3 and 4 studies conducted with DPP-4 inhibitors suggested that their
      use might translate into a better CVD outcome. Data from three CVD outcome RCTs
      with alogliptin, saxagliptin and sitagliptin documented no harm but did not show
      any benefit on major CVD events. A modest but significant increased risk of
      hospitalization for heart failure was observed with saxagliptin and with
      alogliptin (only in subjects with no history of heart failure before
      randomization) but not with sitagliptin. A study currently in progress with
      linagliptin will provide further insights in the issue of CVD safety and benefit.
      CONCLUSIONS: It should be considered that most alternative oral antidiabetic
      agents generally do not possess a better CVD risk profile than DPP-4 inhibitors
      and that some of them, indeed, should be used with caution because of potentially
      adverse effects on heart and vasculature. Overall, the selection of antidiabetic
      agent(s) with the most favourable CVD profile is mandatory but still challenging
      in diabetes care.

PMID- 27038848
TI  - Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II
      inhibitor.
AB  - Elevated levels of carbonic anhydrase II (CA II) have been shown to be associated
      with cardiac hypertrophy and heart failure. Although arjunolic acid (AA) has a
      diverse range of therapeutic applications including cardio-protection, there have
      been no reports on the effect of AA on CA II. The present study describes for the
      first time, the novel zinc independent inhibition of CA II by AA. The molecular
      docking studies of AA indicated that the hydroxyl group at C2 of the A-ring,
      which hydrogen bonds with the catalytic site residues (His64, Asn62 and Asn67),
      along with the gem-dimethyl group at C20 of the E-ring, greatly influences the
      inhibitory activity, independent of the catalytic zinc, unlike the inhibition
      observed with most CA II inhibitors. Among the triterpenoids tested viz.
      arjunolic acid, arjunic acid, asiatic acid, oleanolic acid and ursolic acid, AA
      was the most potent in inhibiting CA II in vitro with an IC50 of 9MUM. It was
      interesting to note, that in spite of exhibiting very little differences in their
      structures, these triterpenoids exhibited vast differences in their inhibitory
      activities, with IC50 values ranging from 9MUM to as high as 333MUM. Furthermore,
      AA also inhibited the cytosolic activity of CA in H9c2 cardiomyocytes, as
      reflected by the decrease in acidification of the intracellular pH (pHi). The
      decreased acidification reduced the intracellular calcium levels, which further
      prevented the mitochondrial membrane depolarization. Thus, these studies provide
      a better understanding for establishing the novel molecular mechanism involved in
      CA II inhibition by the non-zinc binding inhibitor AA.

PMID- 27038849
TI  - Hybrid benzothiazole analogs as antiurease agent: Synthesis and molecular docking
      studies.
AB  - Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and
      (1)H NMR, and evaluated for urease inhibition activity. All compounds showed
      excellent urease inhibitory potential varying from 1.4+/-0.10 to 34.43+/-2.10MUM
      when compared with standard thiourea (IC50 19.46+/-1.20MUM). Among the series
      seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and
      18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed
      good urease inhibition activity. When we compare the activity of N-phenylthiourea
      20 with all substituted phenyl derivatives (1-18) we found that compound 15
      showed less activity than compound 20 having 3-methoxy substituent. The binding
      interactions of these active analogs were confirmed through molecular docking.

PMID- 27038850
TI  - Outcomes in systematic reviews of complex interventions never reached "high"
      GRADE ratings when compared with those of simple interventions.
AB  - OBJECTIVES: To investigate the application of the Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) approach and the quality of
      evidence ratings in systematic reviews of complex interventions. STUDY DESIGN AND
      SETTING: This study examined all 40 systematic reviews published in three
      Cochrane Review Groups from 2013 to May 2014: Cochrane Developmental,
      Psychosocial and Learning Problems Group (CDPLPG); Cochrane Public Health Group
      (CPHG); and Cochrane Depression, Anxiety, and Neurosis Group (CCDAN). The reviews
      were coded and classified into "complex" (n = 24) and "simple" (n = 16)
      intervention review groups based on the predefined complexity dimensions from the
      extant literature mapped into the PICOTS framework. All the data were analyzed in
      these two groups to help identify specific patterns of the GRADE ratings in the
      reviews of complex interventions. RESULTS: Outcomes of complex intervention
      reviews had higher proportions of "very low" quality of evidence ratings compared
      with those of simple intervention reviews (37.5% vs. 9.1% for the primary benefit
      outcomes) and were more frequently downgraded for inconsistency, performance
      bias, and study design. None of the outcomes of complex intervention reviews (0%)
      were given "high" GRADE ratings. CONCLUSION: Results suggest that the GRADE
      assessment may not adequately describe the evidence base of complex
      interventions.

PMID- 27038851
TI  - Response to the commentary on "A nomogram was developed to enhance the use of
      multinomial logistic regression modelling in diagnostic research".

PMID- 27038852
TI  - Psychometric properties of the Neck OutcOme Score, Neck Disability Index, and
      Short Form-36 were evaluated in patients with neck pain.
AB  - OBJECTIVE: To assess reliability, construct validity, responsiveness, and
      interpretability for Neck OutcOme Score (NOOS), Neck Disability Index (NDI), and
      Short Form-36 (SF-36) in neck pain patients. STUDY DESIGN AND SETTING: Internal
      consistency was assessed by Cronbach alpha. Test-retest reliability was evaluated
      by intraclass correlation coefficient (ICC), and measurement error was estimated
      from the standard error of measurement. Responsiveness was assessed as
      standardized response mean (SRM) and interpretability from the minimal important
      difference (MID). Construct validity was tested correlating subscale scores from
      NOOS and SF-36 and NDI items. RESULTS: At baseline, 196 neck pain patients were
      included. Cronbach alpha was adequate for most NOOS subscales, NDI, and SF-36
      with few exceptions. Good to excellent reliability was found for NOOS subscales
      (ICC 0.88-0.95), for NDI, and for SF-36 with few exceptions. For NOOS, minimal
      detectable changes varied between 1.1 and 1.9, and construct validity was
      supported. SRMs were higher for NOOS subscales (0.19-0.42), compared to SF-36 and
      NDI. MID values varied between 15.0 and 24.1 for NOOS subscales. CONCLUSIONS: In
      conclusion, the NOOS is a reliable, valid, and responsive measure of self
      reported disability in neck pain patients, performing at least as well or better
      than the commonly used SF-36 and NDI.

PMID- 27038853
TI  - Inadequate critical appraisal of studies in systematic reviews of time to
      diagnosis.
AB  - OBJECTIVE: To analyze tools used to critically appraise primary studies included
      in systematic reviews (SRs) of time to diagnosis (TTD). STUDY DESIGN AND SETTING:
      We systematically searched MEDLINE via PubMed and Web of Science for SRs of TTD
      published up to the end of February 2015; we identified and characterized tools
      used for critical appraisal and classified their items. RESULTS: From 1,936
      articles identified, we included 45 SRs that aimed to summarize the available
      information on the length (n = 16), determinants (n = 31), and/or consequences (n
      = 14) of TTD. For the 23 SRs (51%) reporting a critical appraisal process, 21
      different tools were used, with 232 items assessing quality of reporting (64%),
      risk of bias or threats to generalizability (43%), statistical issues (5%),
      and/or an unclear domain (0.5%); 11% were specific to TTD issues. Overall, 36% of
      the 45 SRs assessed risk of bias and/or threats to generalizability. CONCLUSION:
      Assessment of risk of bias and threats to generalizability in primary studies
      included in SRs of TTD is infrequent, nonstandardized and rarely concerns TTD
      study specificities. These findings highlight the need for guidance on critical
      appraisal of studies of TTD.

PMID- 27038854
TI  - Perioperative complications in open versus percutaneous treatment of spinal
      fractures in patients with an ankylosed spine.
AB  - We compared open stabilization of vertebral fractures to percutaneous spinal
      fixation techniques in patients with a diagnosis of either ankylosing spondylitis
      (AS) or diffuse idiopathic skeletal hyperostosis (DISH). A retrospective review
      of patients known to have AS or DISH treated for spinal column fracture at a
      single institution between 1995 and 2011 was performed. Patients were analyzed by
      the type of fixation, divided into either a percutaneous group (PG) or an open
      group (OG). There were 41 patients identified with a spinal column fracture and
      history of AS or DISH who received surgical intervention. There were 17 (42%)
      patients with AS and 24 (58%) with DISH. Patients in the PG and OG cohorts
      presented with similar mechanisms of injury, Injury Severity Scale, number of
      vertebral fractures, number of additional injuries, and Arbeitsgemeinschaft fur
      Osteosynthesefragen (AO) classification scores. Mean operative time
      (254.76minutes versus 334.67minutes, p=0.040), estimated blood loss (166.8 versus
      1240.36mL, p<0.001), blood transfusion volume (178.32 versus 848.69mL, p<0.001),
      and time to discharge (9.58 days versus 16.73 days, p=0.008) were significantly
      less in the PG cohort. The rate of blood transfusion (36% versus 87.5%, p=0.001)
      and complications (56% versus 87%, p=0.045) were significantly less in the PG
      cohort. Percutaneous stabilization of fractures in patients with AS or DISH was
      associated with lower blood loss, shorter operative times and decreased need for
      transfusion, shorter hospitalization time and a lower perioperative complication
      rate. 

PMID- 27038855
TI  - [Chronic or recurrent ulceration of the tongue].

PMID- 27038856
TI  - Effects of Intraoperative Hemodynamics on Incidence of Postoperative Delirium in
      Elderly Patients: A Retrospective Study.
AB  - BACKGROUND: Postoperative delirium (POD) is a common complication in the elderly.
      This retrospective study investigated the effect of intraoperative hemodynamics
      on the incidence of POD in elderly patients after major surgery to explore ways
      to reduce the incidence of POD. MATERIAL/METHODS: Based on the incidence of POD,
      elderly patients (81+/-6 y) were assigned to a POD (n=137) or non-POD group
      (n=343) after elective surgery with total intravenous anesthesia. POD was
      diagnosed based on the guidelines of the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV), using the confusion assessment method.
      The hemodynamic parameters, such as mean arterial pressure, were monitored 10 min
      before anesthesia (baseline) and intraoperatively. The incidence of
      intraoperative hypertension, hypotension, tachycardia, and bradycardia were
      calculated. RESULTS: At 30 min and 60 min after the initiation of anesthesia and
      at the conclusion of surgery, the monitored hemodynamic parameter values of the
      POD group, but not those of the non-POD group, were significantly higher than at
      baseline. Multivariate logistic regression analysis showed that intraoperative
      hypertension and tachycardia were significantly associated with POD. CONCLUSIONS:
      Intraoperative hypertension and tachycardia were significantly associated with
      POD. Maintaining intraoperative stable hemodynamics may reduce the incidence of
      POD in elderly patients undergoing surgery.

PMID- 27038857
TI  - Advanced purification strategy for CueR, a cysteine containing copper(I) and DNA
      binding protein.
AB  - Metal ion regulation is essential for living organisms. In prokaryotes metal ion
      dependent transcriptional factors, the so-called metalloregulatory proteins play
      a fundamental role in controlling the concentration of metal ions. These proteins
      recognize metal ions with an outstanding selectivity. A detailed understanding of
      their function may be exploited in potential health, environmental and analytical
      applications. Members of the MerR protein family sense a broad range of mostly
      late transition and heavy metal ions through their cysteine thiolates. The air
      sensitivity of latter groups makes the expression and purification of such
      proteins challenging. Here we describe a method for the purification of the
      copper-regulatory CueR protein under optimized conditions. In order to avoid
      protein precipitation and/or eventual aggregation and to get rid of the co
      purifying Escherichia coli elongation factor, our procedure consisted of four
      steps supplemented by DNA digestion. Subsequent anion exchange on Sepharose FF Q
      16/10, affinity chromatography on Heparin FF 16/10, second anion exchange on
      Source 30 Q 16/13 and gel filtration on Superdex 75 26/60 resulted in large
      amounts of pure CueR protein without any affinity tag. Structure and
      functionality tests performed with mass spectrometry, circular dichroism
      spectroscopy and electrophoretic gel mobility shift assays approved the success
      of the purification procedure.

PMID- 27038858
TI  - Structural brain correlates of defective gesture performance in schizophrenia.
AB  - INTRODUCTION: The neural correlates of impaired performance of gestures are
      currently unclear. Lesion studies showed variable involvement of the ventro
      dorsal stream particularly left inferior frontal gyrus (IFG) in gesture
      performance on command. However, findings cannot be easily generalized as lesions
      may be biased by the architecture of vascular supply and involve brain areas
      beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares
      apraxic-like errors and altered brain structure without macroanatomic lesions.
      Schizophrenia may therefore qualify as a model disorder to test neural correlates
      of gesture impairments. METHODS: We included 45 schizophrenia patients and 44
      healthy controls in the study to investigate the structural brain correlates of
      defective gesturing in schizophrenia using voxel based morphometry. Gestures were
      tested in two domains: meaningful gestures (transitive and intransitive) on
      verbal command and imitation of meaningless gestures. Cut-off scores were used to
      separate patients with deficits, patients without deficits and controls. Group
      differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS:
      Patients performed poorer than controls in each gesture category (p < .001).
      Patients with deficits in producing meaningful gestures on command had reduced GM
      predominantly in left IFG, with additional involvement of right insula and
      anterior cingulate cortex. Patients with deficits differed from patients without
      deficits in right insula, inferior parietal lobe (IPL) and superior temporal
      gyrus. CONCLUSIONS: Impaired performance of meaningful gestures on command was
      linked to volume loss predominantly in the praxis network in schizophrenia. Thus,
      the behavioral similarities between apraxia and schizophrenia are paralleled by
      structural alterations. However, few associations between behavioral impairment
      and structural brain alterations appear specific to schizophrenia.

PMID- 27038859
TI  - The contribution of the pineal gland on daily rhythms and masking in diurnal
      grass rats, Arvicanthis niloticus.
AB  - Melatonin is a hormone rhythmically secreted at night by the pineal gland in
      vertebrates. In diurnal mammals, melatonin is present during the inactive phase
      of the rest/activity cycle, and in primates it directly facilitates sleep and
      decreases body temperature. However, the role of the pineal gland for the
      promotion of sleep at night has not yet been studied in non-primate diurnal
      mammalian species. Here, the authors directly examined the hypothesis that the
      pineal gland contributes to diurnality in Nile grass rats by decreasing activity
      and increasing sleep at night, and that this could occur via effects on circadian
      mechanisms or masking, or both. Removing the pineal gland had no effect on the
      hourly distribution of activity across a 12:12 light-dark (LD) cycle or on the
      patterns of sleep-like behavior at night. Masking effects of light at night on
      activity were also not significantly different in pinealectomized and control
      grass rats, as 1h pulses of light stimulated increases in activity of sham and
      pinealectomized animals to a similar extent. In addition, the circadian
      regulation of activity was unaffected by the surgical condition of the animals.
      Our results suggest that the pineal gland does not contribute to diurnality in
      the grass rat, thus highlighting the complexity of temporal niche transitions.
      The current data raise interesting questions about how and why genetic and neural
      mechanisms linking melatonin to sleep regulatory systems might vary among mammals
      that reached a diurnal niche via parallel and independent pathways. 

PMID- 27038860
TI  - Cord Blood Units with High CD3(+) Cell Counts Predict Early Lymphocyte Recovery
      After In Vivo T Cell-Depleted Single Cord Blood Transplantation.
AB  - Although high absolute lymphocyte count (ALC) early after transplantation is a
      simple surrogate for immune reconstitution, few studies to date have established
      the predictive factors for ALC after umbilical cord blood transplantation (UCBT).
      We retrospectively studied the factors associated with early lymphocyte recovery
      and the impact of the ALC on day +42 (ALC42) of >=300 * 10(6)/L on outcomes in
      210 consecutive pediatric and adult patients (112 males; median age, 15 years;
      range, 0.3 to 60 years; interquartile range, 4 to 36 years) who underwent
      myeloablative in vivo T cell-depleted single UCBT between 2005 and 2014 for
      malignant and nonmalignant disorders. In a logistic multivariate regression
      model, factors favoring a higher ALC42 were higher infused CD3(+) cell dose (odds
      ratio [OR], 2.7; 95% CI, 1.4 to 5.2; P = .004), lower antithymocyte globulin dose
      (OR, 2.3; 95% CI, 1.2 to 4.5; P = .01), and better HLA match (OR, 2.1; 95% CI,
      1.1 to 4.1; P = .03). In multivariate analysis, lower ALC42 was associated with
      higher nonrelapse mortality (hazard ratio [HR], 1.76; 95% CI, 1.34 to 2.32; P =
      .001), whereas a higher ALC42 was associated with better disease-free survival
      (HR, 2.03; 95% CI, 1.15 to 3.6; P < .001) and overall survival (HR, 2.03; 95% CI,
      1.17 to 3.6; P < .001). Our study suggests that the selection of better HLA
      matched cord blood units containing higher CD3(+) cell counts and the use of
      conditioning regimens with lower ATG doses could improve immune reconstitution
      after UCBT.

PMID- 27038861
TI  - Secondary Patellar Resurfacing as a Rescue Procedure for Persistent Anterior Knee
      Pain After Primary Total Knee Arthroplasty: Do Our Patients Really Improve?
AB  - BACKGROUND: Secondary patellar resurfacing (SPR) is a procedure that can be used
      in patients with persistent anterior knee pain (AKP) after a primary total knee
      arthroplasty. The aim of our study was to analyze the clinical and functional
      outcomes as well as the complications of this procedure and identify predictive
      factors for a favorable outcome. METHODS: Forty-six patients who underwent SPR
      for persistent AKP after primary total knee arthroplasty were retrospectively
      studied. The patient's mean age was 68 years (range, 36-86 years). The average
      follow-up time after SPR was 74 months (range, 24-197 months). Demographic data,
      Knee Society Score scale, range of motion, pain improvement (Visual Analogue
      Scale), overall satisfaction, and complications were recorded. The statistical
      analysis was performed using STATA tm/SE v10. RESULTS: There was an improvement
      of the Knee Society scale (from 54 +/- 11 to 64 +/- 16 points; P < .05). However,
      in 59% of the cases, there was no pain improvement, and 65% of patients were not
      satisfied. Four patients showed complications, and in 2 cases, reoperation was
      necessary. We did not find any preoperative predictive factor for a favorable
      outcome after SPR. CONCLUSION: Despite improvement of the Knee Society scale,
      many patients continue with AKP and are dissatisfied with this procedure;
      therefore, we do not recommend it in this clinical scenario.

PMID- 27038862
TI  - The Valgus Inclination of the Tibial Component Increases the Risk of Medial
      Tibial Condylar Fractures in Unicompartmental Knee Arthroplasty.
AB  - BACKGROUND: Medial tibial condylar fractures (MTCFs) are a rare but serious
      complication after unicompartmental knee arthroplasty. Although some surgical
      pitfalls have been reported for MTCFs, it is not clear whether the varus/valgus
      tibial inclination contributes to the risk of MTCFs. METHODS: We constructed a 3
      dimensional finite elemental method model of the tibia with a medial component
      and assessed stress concentrations by changing the inclination from 6 degrees 
      varus to 6 degrees  valgus. Subsequently, we repeated the same procedure adding
      extended sagittal bone cuts of 2 degrees  and 10 degrees  in the posterior tibial
      cortex. Furthermore, we calculated the bone volume that supported the tibial
      component, which is considered to affect stress distribution in the medial tibial
      condyle. RESULTS: Stress concentrations were observed on the medial tibial
      metaphyseal cortices and on the anterior and posterior tibial cortices in the
      corner of cut surfaces in all models; moreover, the maximum principal stresses on
      the posterior cortex were larger than those on the anterior cortex. The extended
      sagittal bone cuts in the posterior tibial cortex increased the stresses further
      at these 3 sites. In the models with a 10 degrees  extended sagittal bone cut,
      the maximum principal stress on the posterior cortex increased as the tibial
      inclination changed from 6 degrees  varus to 6 degrees  valgus. The bone volume
      decreased as the inclination changed from varus to valgus. CONCLUSION: In this
      finite element method, the risk of MTCFs increases with increasing valgus
      inclination of the tibial component and with increased extension of the sagittal
      cut in the posterior tibial cortex.

PMID- 27038863
TI  - Soft Tissue Reconstruction and Flap Coverage for Revision Total Knee
      Arthroplasty.
AB  - BACKGROUND: Total knee arthroplasty is a successful operation for treatment of
      arthritis. However, devastating wound complications and infections can compromise
      the knee joint, particularly in revision situations. METHODS: Soft tissue loss
      associated with poor wound healing and multiple operations can necessitate the
      need for reconstruction for wound closure and protection of the prosthesis.
      RESULTS: Coverage options range from simple closure methods to complex
      reconstruction, including delayed primary closure, healing by secondary
      intention, vacuum-assisted closure, skin grafting, local flap coverage, and
      distant microsurgical tissue transfer. CONCLUSION: Understanding the advantages
      and pitfalls of each reconstructive option helps to guide treatment and avoid
      repeated operations and potentially devastating consequences such as knee
      arthrodesis or amputation.

PMID- 27038864
TI  - Toward the Turkish National Registry System: A Prevalence Study of Total Knee
      Arthroplasty in Turkey.
AB  - BACKGROUND: The aim of this pilot study was to analyze the data obtained from a
      retrospective examination of the records of the existing reimbursement system and
      through the identification of gaps in the data to create a foundation for a
      reliable, descriptive national registry system for our country. METHODS: The
      Social Security Institution Medical Messenger (MEDULA) records were scanned for
      the years 2010-2014, and the numbers of total knee arthroplasty applied for a
      diagnosis of gonarthrosis and the numbers of revision knee arthroplasty were
      recorded for the country in general. The patients were classified according to
      age, gender, and bilateral or unilateral surgery. The institution where the
      surgery was applied, the geographic region and the province were also recorded.
      RESULTS: A total of 283,400 primary and 9900 revision knee arthroplasty
      operations were applied in Turkey between 2010 and 2014. Numbers were recorded
      for each year, and there was found to be an increase between years. For primary
      knee arthroplasty, the female:male ratio was 67 of 33, and surgery was applied
      most often between the ages of 60-69 years. Both types of surgery were determined
      to have been applied most often in second-stage state hospitals. Geographically,
      both types of surgery were applied most in the Marmara region, with the highest
      frequency of primary knee arthroplasty in Istanbul and the highest frequency of
      revision surgery in Ankara. CONCLUSIONS: The data obtained from this study will
      contribute to the creation of the basis for a National Registry System and
      thereby define more scientific treatment approaches.

PMID- 27038865
TI  - Urine and serum biomonitoring of exposure to environmental estrogens I: Bisphenol
      A in pregnant women.
AB  - Despite its very low oral bioavailability and rapid elimination, multiple reports
      of unexpectedly high bisphenol A (BPA) concentrations in the serum of pregnant
      mothers or cord blood have raised questions about BPA exposures during pregnancy.
      Thirty healthy pregnant women recruited to the study were evaluated for total BPA
      exposure over a 30-h period comprising one-half day in the field and one day in a
      clinical setting. BPA and its metabolites were measured in serum and total BPA
      was measured in matching urine samples. The mean total exposure was similar to
      the 50(th) percentile of exposure for U.S. women and pregnant women in a large
      North American cohort. Twenty volunteers had total daily exposures equal to or
      exceeding the U.S. mean, and six volunteers had exposures exceeding the 75th
      percentile. Women working as cashiers did not have higher total BPA exposure. BPA
      was detected in some serum samples (0.25-0.51 ng/ml), but showed no relationship
      to total BPA in corresponding urine samples, no relationship to total BPA
      exposure, and had unconjugated BPA fractions of 60-80%, consistent with
      established criteria for sample contamination. We conclude that typical exposures
      of North American pregnant women produce internal exposures to BPA in the
      picomolar range. 

PMID- 27038866
TI  - ['Hit and run': The old paradigm of psychopharmacology in a new coat' -
      Editorial].

PMID- 27038867
TI  - [Alzheimer's disease and diabetes - the common pathogenesis].
AB  - Epidemiological studies presented evidence that Alzheimer's disease and type 2
      diabetes share common features in their pathophysiology and clinical patterns.
      Insulin resistance is a characteristic feature of both diseases. According to the
      pathomechanism, inflammatory, metabolic, and an atypical form based on the
      deficiency of zinc ions can be distinguished. Glucose metabolic disorders,
      related to Alzheimer's disease, are type 2 diabetes, and prediabetes/metabolic
      syndrome. Based on the common pathophysiological patterns of these two diseases,
      Alzheimer's disease is customary called type 3 diabetes. In the research on
      dementias, insulin resistance stands in the highlight for its documented harmful
      effects on cognitive function and causes dementia. Insulin-like growth factor
      also influences cognitive functions. Reduced input of this hormone into the brain
      may also cause dementia, however literary data are controversial. In Alzheimer's
      disease, deposition of amyloid beta in the brain, hyperphosphorylation of tau
      proteins and dysruption of neurofibrilles are characteristic. Amyloid beta is co
      secreted in the beta-cells of the pancreas with insulin. Amyloid beta and
      hyperphosphorylated tau protein were detected in the Langerhans islets by
      autopsy. Amyloid deposits, found in the pancreas and brain presented
      similarities. As a consequence of hyperglycemia, glycation endproducts cause the
      development of amyloid plaques, dysruption of neurofibrilles, and activated
      microglia, all are typical to Alzheimer's disease. Continuous hyperglycemia leads
      to oxidative stress, which used to play significant role in the development of
      both diseases. Low-grade inflammation is also a significant pathophysiological
      factor in both disorders. The sources of inflammation are proinflammatorical
      adipocytokines, dysbacteriosis, metabolic endotoxaemia, caused by
      lipopolysaccharides, and high fat diet which also lead to insulin resistance.
      Based on recent data, microbial amyloid, the main product of bacteria, is also
      contributing to the pathophysiology of the human central nervous system.
      Alzheimer's disease is a heterogeneous disorder, and as yet there is no effective
      therapy. Encouraging results have emerged by using intranasal insulin spray.
      Insulin sensitizers like metformin, thiazolidines have also resulted in
      improvements in cognitive functions, mainly in animal experiments. Glucagon-like
      peptide-1, beyond its insulin-stimulating effect, also has central pleiotropic
      influences. Research results with the application of these molecules seem to be
      enouraging. More recently, glucagon-like peptide-1, and glucose-dependent
      insulinotropic peptide were administered together, with promising early results.
      The real breakthrough has not yet arrived. For the time being we have to
      endeavour to the prevention of both chronic diseases via a more healthy life
      style.

PMID- 27038868
TI  - [Autotelic activities aimed at the alteration of the human body from socially
      accepted to pathological forms: about non-suicidal self-injury].
AB  - The author lays down that non-suicidal self-injury (NSSI) constitutes an
      increasingly more common and serious public health problem, especially during the
      age of adolescence. In spite of the fact that the phenomenon has been known since
      the beginning of human mankind even in animals, we have not been able to either
      give a clear explanation or prevent its spreading yet. The author reviews the
      conceptual disturbances, behavioural phenotypes, cultural-historical and
      mythological antecedents related to self-injury, just as the controversial
      concepts, reasons of unclearness of the concepts, and clinical classification of
      self-injuries, and he outlines a new categorisation/ classification of the
      explanation of autotelic activities aimed at the alteration of the human body. He
      reviews the relationship between self-injuries and other psychological signs and
      symptoms and psychiatric illnesses, the explanations of developing self-injurious
      behaviour and further research directions. Besides the different models of self
      injury he presents a holistic model. Besides the therapeutic guidelines of self
      injurious behaviour, he calls the attention to the importance of genetic and
      nervous system researches, psychological and spiritual research, the importance
      of mental education and prevention, and he also lists some more essential
      questions future researchers have to find the answers for if we would like all
      children to be allowed to enter the adults' world in a healthy and sound state.

PMID- 27038869
TI  - [Possible effects of climate changes (particularly heat waves) on body functions
      with a special emphasis on subjects taking psychopharmacons: a narrative review].
AB  - Climate change and global warming have become increasingly discussed in the last
      few years - but mainly as an economical-social problem. Due to the preceding
      years' hot summers, as a clinical psychiatrist I considered it important to
      examine the effect of heat on body functions especially among those who are
      taking psychiatric drugs. The problem has a clinical significance, since heat is
      an extreme environmental factor with unexpected consequences. Due to heat various
      adverse reactions are expected especially in subjects on combined pharmacotherapy
      regimes. The present article points out the clinical importance of heat and also
      its potential adverse (and sometimes life-threatening) consequences.

PMID- 27038870
TI  - [Iowa Gambling Task: illustration of a behavioral measurement].
AB  - The Iowa Gambling Task is a behavioral measurement which was developed to examine
      decision-making based on the Somatic Marker Hypothesis. Participants have to make
      series of choices altogether 100 times from four decks of cards. The decks have
      different characteristics with regards to gains and losses. After the initial
      analyses - with a focus on patients with damage to the ventromedial prefrontal
      cortex - the tool soon became one of the most frequently used technique of
      measuring hot executive functions. It is also used to measure impulsivity.
      Structures involved in decision-making constitute the neural basis of the Task.
      IGT is applied in several different disorders (in connection with decision-making
      and impulsivity as well). In recent years different versions have been developed,
      and these modifications may have different effects on IGT performance, and may
      also influence what the Task measures exactly. With growing empirical evidence
      several questions have arisen in connection with the composition of the decks
      (gain-loss magnitude vs. frequency, prominent deck B phenomenon) which suggest to
      use other indexes as well besides the net scores.

PMID- 27038871
TI  - [Changes in quality of life and work function during phase prophylactic
      lamotrigine treatment in bipolar patients: 6 month, prospective, observational
      study].
AB  - Bipolar disorder is a lifelong illness requiring lifelong pharmacotherapy.
      Therefore besides symptomatic remission, achievement of full work-related
      functioning and restoration of quality of life is a priority during successful
      treatment. The present prospective, observational, non-intervention study focused
      on investigating the effect of lamotrigine therapy on the quality of life and
      work-related function of bipolar patients in outpatient care. METHODS: 969
      bipolar or schizoaffective outpatients participated in the study who previously
      did not receive lamotrigine therapy. Our present phase-prophylactic study was a
      prospective, observational, non-intervention study with a six-month follow-up.
      Evaluations took place at baseline and at months 1, 2, 3 and 6. Patients were
      followed with a Clinical Global Impression-Severity (CGI-S) and Clinical Global
      Impression-Improvement (CGI-I). Changes in work-related function was evaluated
      using Social Adjustment Scale (SAS), while quality of life was assessed with the
      Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scale.
      RESULTS: SAS scoreds showed a consistent decrease in the overall sample and in
      all CGI-S initial groups reflecting the improvement of work-related function
      during the six months of the follow-up. Q-LES-Q values in the whole sample and in
      all initial CGI-S groups showed a steady increase indicating a continuous
      increase in quality of life during the study. CONCLUSION: Our results indicate
      that during long-term prophylactic lamotrigine therapy the work function and
      quality of life of bipolar patients shows a significant improvement, therefore
      lamotrigine provides a possibility for full functional remission and restoration
      of quality of life.

PMID- 27038872
TI  - Prevalence of the accessory deep peroneal nerve: A cadaveric study and meta
      analysis.
AB  - OBJECTIVES: The accessory deep peroneal nerve (ADPN) is a common anatomical
      variant arising from the superficial peroneal nerve (SPN) and, when present, is
      often responsible for partial or complete innervation of the extensor digitorum
      brevis muscle (EDBM). The nerve lies posterior to the peroneus brevis muscle,
      traveling posterior to the lateral malleolus to terminate in the ankle by giving
      off sensory branches to the ankle and joints. Although the EDBM is usually
      supplied by the deep peroneal nerve (DPN), in the presence of an ADPN,
      electrodiagnostic procedures may be complicated. Due to the lack of detailed
      anatomical knowledge on the topography of the ADPN, its presence posterior to the
      lateral malleolus can be iatrogenically injured during surgical procedures on the
      ankle using a lateral approach. Therefore, this meta-analysis aimed to provide a
      comprehensive, evidence-based assessment of the anatomical characteristics of the
      ADPN, supplemented with data from our own cadaveric dissection. PATIENTS AND
      METHODS: A comprehensive search of all major electronic databases, including
      Pubmed, Embase, Scopus, Web of Science, ScienceDirect, SciELO, and BIOSIS was
      performed. All articles with data on prevalence, symmetry and innervation of the
      EDBM by the ADPN were included. The anatomical data was then extracted and pooled
      into a meta-analysis using MetaXL 2.0. In addition, we dissected 21 cadavers
      (n=42 lower limbs) bilaterally to find the ADPN. RESULTS: A total of 19 studies
      (n=6070 lower limbs) were included in the meta-analysis. The pooled prevalence of
      the ADPN was 18.8% (95%CI:14.2-24.0) with a 39.3% prevalence rate for cadaveric
      studies. The ADPN was present more commonly unilaterally (67.0%) and when it was
      present, provided branches to the EDBM in 79.5% of cases. In our cadaveric study,
      the ADPN was identified in 5 of the 42 lower limbs dissected (11.9%); on the
      right side in 3 lower limbs and on the left side in 2 lower limbs. CONCLUSIONS:
      The ADPN is a clinically important nerve and has been inculpated in unexplained
      cases of chronic ankle pain and EDBM atrophy. The variability in detection of the
      ADPN using electrophysiological techniques can lead to misdiagnoses of peroneal
      nerve lesions and increase the risk for iatrogenic injury to the ADPN, especially
      in laterally approaching ankle procedures and sural nerve biopsies.

PMID- 27038873
TI  - Hypopituitarism patterns among adult males with prolactinomas.
AB  - OBJECTIVES: The objective of this study was to characterize hypopituitarism in
      adult males with prolactinomas. PATIENTS AND METHODS: We retrospectively analyzed
      the records of 102 consecutive patients, classified under three categories based
      on adenoma size at diagnosis: 1.0-2.0cm (group A), 2.1-4.0cm (group B), and
      >4.0cm (group C). Further, 76 patients had successful outcomes at follow-up. We
      compared different forms of pituitary hormone dysfunction (growth hormone
      deficiency, hypogonadism, hypothyroidism, and hypocortisolism) based on the
      maximal adenoma diameter. RESULTS: Serum prolactin levels were significantly
      correlated with the maximal adenoma diameter (r=0.867; P=0.000). Of the patients,
      89.2% presented with pituitary failure, which included 74.5% with growth hormone
      deficiency, 71.6% with hypogonadism, 28.4% with hypothyroidism, and 12.7% with
      hypocortisolism. The three groups did not differ significantly (P>0.05) in the
      incidence of hypopituitarism, including the extent of pituitary axis deficiency,
      at presentation and following treatment. However, there was a statistically
      significant difference in the degree of hypogonadism in cases of acquired
      pituitary insufficiency at diagnosis (P=0.000). CONCLUSION: In adult males with
      prolactin-secreting adenomas, the most common form of pituitary hormone
      dysfunction was growth hormone deficiency and hypogonadism, whereas
      hypocortisolism was less common. The maximal adenoma diameter and prolactin
      secretion did not determine hormone insufficiency in adult males with
      prolactinomas, but these factors did affect the degree of both hypogonadism and
      hypothyroidism. Smaller tumors were found to recur more frequently than large
      tumors, and recovery was more common in cases of growth hormone deficiency and
      hypogonadism.

PMID- 27038874
TI  - Fluorescein assistance in neuro-oncological surgery: A trend of the moment or a
      real technical adjunt?

PMID- 27038875
TI  - Changes in brain peptides associated with reproduction and energy homeostasis in
      photosensitive and photorefractory migratory redheaded buntings.
AB  - Present study examined the expression of brain peptides associated with the
      reproduction and energy homeostasis (GnRH/GnIH, NPY/VIP), and assessed their
      possible functional association in the photosensitive (non-breeding, pre
      breeding), photostimulated (breeding) and photorefractory (post-breeding)
      migratory redheaded buntings (Emberiza bruniceps), using double-labeled
      immunohistochemistry. Particularly, we measured immunoreactive (-ir) cell
      numbers, per cent cell area and cell optical density (OD) in the preoptic area
      (GnRH-I), midbrain (GnRH-II), paraventricular nucleus (GnIH), dorsomedial
      hypothalamus, DMH and infundibular complex, INc (NPY and VIP), and lateral septal
      organ (VIP) of buntings kept under natural photoperiods at the wintering latitude
      (26 degrees 55'N). There was a significant seasonal difference in GnRH-I, not
      GnRH-II, with reduced -ir cells in the photosensitive and photorefractory
      buntings, and notably with increased cell OD between the refractory and non
      breeding states with no increase in testis size. Also, increased cell OD of GnIH
      neurons in non-breeding state indicated its role in the maintenance of small
      testes during the post-refractory period. Overall, seasonal changes in GnRH-I and
      GnIH were found consistent with their suggested roles in reproductive regulation
      of absolute photorefractory birds. Further, there was a significant seasonal
      change in cell OD of NPY neurons in DMH, not the INc. In contrast, VIP
      immunoreactivity was seasonally altered, with a significantly higher VIP-ir cells
      in breeding than the pre-breeding state. Finally, close proximity between
      perikarya with fibres suggested functional interactions between the GnRH and
      GnIH, and NPY and VIP. Thus, seasonal plasticity of brain peptides is perhaps the
      part of neural regulation of seasonal reproduction and associated energy
      homeostasis in migratory songbirds.

PMID- 27038876
TI  - Russelioside B, a pregnane glycoside ameliorates hyperglycemia in streptozotocin
      induced diabetic rats by regulating key enzymes of glucose metabolism.
AB  - An alternative strategy to treat diabetes mellitus is the use of various natural
      agents possessing hypoglycemic effect. Caralluma quadrangula has been used in
      Saudi traditional medicine in cases of thirst and hunger and for the treatment of
      diabetes. The present study was designed to evaluate the improving effect of
      russelioside B, a pregnane glycoside isolated from Caralluma quadrangula on
      glucose metabolism in the liver of streptozotocin-induced diabetic rats. Diabetes
      mellitus was induced in rats by a single intraperitoneal injection of
      streptozotocin (50 mg/kg body weight). Experimental rats were administered
      russelioside B at a dose of 50 mg/kg body weight once a day for 30 days. The
      results showed that RB improved the fasting serum glucose level, glycated
      hemoglobin percent, serum insulin level and lipid profile. A significant
      improvement was observed upon the administration of russelioside B on the
      activities of the key enzymes of carbohydrate metabolism (glucokinase, glucose-6
      phosphatase, glucose-6-phosphate dehydrogenase, and glycogen phosphorylase) in
      the liver of diabetic rats. Further, russelioside B administration to diabetic
      rats reverted gene expression of glucokinase, glucose-6-phosphatase, glycogen
      synthase and glycogen synthase kinase-3beta to near normal levels. In conclusion,
      russelioside B possess antidiabetic and antihyperlipidemic effect in
      streptozotocin induced diabetic rats. Hence, administration of russelioside B may
      represent a potentially useful strategy for the management of diabetes. 

PMID- 27038877
TI  - Methotrexate administration induces differential and selective protein tyrosine
      nitration and cysteine nitrosylation in the subcellular organelles of the small
      intestinal mucosa of rats.
AB  - Gastrointestinal toxicity is one of the most frequent dose limiting side effects
      of methotrexate (MTX), a commonly used chemotherapeutic drug. Peroxynitrite (PON)
      overproduction is reported to contribute to MTX induced gastrointestinal
      mucositis. However, the consequence of PON overproduction i.e. protein tyrosine
      nitration and protein cysteine nitrosylation, the subcellular distribution of
      these modified proteins and their molecular weights have not been investigated
      yet. Mucositis was induced in Wistar rats by the administration of 3 consecutive
      i.p. injections of MTX. Tyrosine nitrated proteins and cysteine nitrosylated
      proteins were determined in the subcellular organelles fractions of mucosa using
      immunoprecipitation and western blot. The proteins in the subcellular fractions
      were separated by 1D electrophoresis, and probed with anti -nitrotyrosine
      antibody and anti-nitrosocysteine antibody. After MTX treatment, a general
      increase in protein tyrosine nitration as well as a change in the spectrum of
      proteins that underwent nitration was observed. The relative densities of the 3
      nitrotyrosine protein adducts were as follows: Mitochondria > cytosol >
      microsomes > nucleus. In the mitochondrial fraction increased nitration of 12
      kDa, 25 kDa 29Kda, 47 kDa, and 62Kda proteins, in the cytosol increased nitration
      of 12 kDa, 19 kDa, 45 kDa, and 60 kDa proteins and in the nuclear fraction
      increased nitration of 17 kDa, 35 kDa, and 58 kDa proteins was observed. On the
      other hand, MTX treatment resulted to a general decrease in protein cysteine
      nitrosylation in all the subcellular fractions. These results suggest that MTX
      induced, PON mediated small intestinal injury is mediated by differential
      nitration and nitrosylation of proteins in the subcellular organelles with
      increased protein tyrosine nitration and decreased cysteine nitrosylation. In
      addition MTX treatment results in selective nitration and nitrosylation of
      proteins in the intestinal mucosa. This differential nitrosative modifications
      may contribute to MTX induced small intestinal injury.

PMID- 27038878
TI  - From early prophylaxis to delayed treatment: Establishing the plutonium
      decorporation activity window of hydroxypyridinonate chelating agents.
AB  - The potential consequences of a major radiological event are not only large-scale
      external radiation exposure of the population, but also uncontrolled
      dissemination of, and internal contamination with, radionuclides. When planning
      an emergency response to radiological and nuclear incidents, one must consider
      the need for not only post-exposure treatment for contaminated individuals, but
      also prophylactic measures to protect the workforce facing contaminated areas and
      patients in the aftermath of such events. In addition to meeting the desired
      criteria for post-exposure treatments such as safety, ease of administration, and
      broad-spectrum efficacy against multiple radionuclides and levels of challenge,
      ideal prophylactic countermeasures must include rapid onset; induce minimal to no
      performance-decrementing side effects; be compatible with current military
      Chemical, Biological, Radiological, Nuclear, and Explosive countermeasures; and
      require minimal logistical burdens. Hydroxypyridinone-based actinide
      decorporation agents have shown the most promise as decorporation strategies for
      various radionuclides of concern, including the actinides plutonium and
      americium. The studies presented here probe the extent of plutonium decorporation
      efficacy for two chelating agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO),
      from early pre-exposure time points to a delay of up to 7 days in parenteral or
      oral treatment administration, i.e., well beyond the initial hours of emergency
      response. Despite delayed treatment after a contamination event, both ligands
      clearly enhanced plutonium elimination through the investigated 7-day post
      treatment period. In addition, a remarkable prophylactic efficacy was revealed
      for 3,4,3-LI(1,2-HOPO) with treatment as early as 48 h before the plutonium
      challenge. This work provides new perspectives in the indication and use of
      experimental actinide decorporation treatments.

PMID- 27038879
TI  - Isolation of aluminum-tolerant bacteria capable of nitrogen removal in activated
      sludge.
AB  - Four strains of bacteria capable of withstanding 20mM concentration of aluminum
      were isolated from activated sludge in a bioreactor. 16S rRNA identification and
      morphological characteristics indicated that these strains were Chryseobacterium
      sp. B1, Brevundimonas diminuta B3, Hydrogenophaga sp. B4, and Bacillus cereus B5.
      Phylogenetic analysis revealed the position and interrelationships of these
      bacteria. B. diminuta B3 and Hydrogenophaga sp. B4 could achieve nitrate nitrogen
      removal of 94.0% and 76.8% within 36h of its initial concentration of 148.8 and
      151.7mg/L, respectively. Meanwhile, B3 and B4 could degrade ammonia with little
      nitrite accumulation. Results of this study provide more information about
      aluminum-resistant bacteria and laid the foundation for aluminum salt when it is
      simultaneously used for chemical precipitation. 

PMID- 27038880
TI  - Effects of H2S injection on the CO2-brine-sandstone interaction under 21MPa and
      70 degrees C.
AB  - In this study, laboratory experiments were conducted to investigate the
      influences of H2S injection on the capacity of CO2's solubility trapping and
      mineral trapping. Results demonstrated that the preferential dissolution of H2S
      gas into brine (compared with pure CO2) resulted in the decrease of pH,
      consequently inhibiting the CO2's solubility trappings to some extent. Then, the
      lower pH droved more severe corrosion of primary minerals, favored more secondary
      mineral to be formed. In addition, the discovery of pyrite demonstrated that H2S
      could precipitate by the formation of sulfide mineral trapping. As the secondary
      carbon sink minerals, ankerite and dawsonite were observed in the pure CO2-brine
      sandstone interaction. However, there were no secondary carbonates found through
      the SEM images and EDS analyses, implied that the injection of H2S probably may
      partially inhibit the precipitation of Fe-bearing carbonate minerals such as
      ankerite in the CO2-H2S-brine-sandstone interaction in this short term
      experiments. 

PMID- 27038881
TI  - Ecological risk, source and preliminary assessment of metals in the surface
      sediments of Chabahar Bay, Oman Sea.
AB  - In this study, concentrations of Aluminum (Al), Iron (Fe), Chromium (Cr), Copper
      (Cu), Nickel (Ni), Vanadium (V), Zinc (Zn), Arsenic (As), Cobalt (Co) and lead
      (Pb) in the surface sediments from Chabahar Bay were studied to assess the degree
      of heavy metal pollution as a consequence of natural and anthropogenic sources.
      Metal contents in the sediments were observed in the order of:
      Al>Fe>Cr>V>Ni>Zn>Cu>>As>Pb>Co. According to enrichment factor (EF), Arsenic was
      higher than 1.5 at some sites, indicating anthropogenic inputs. Contents of Ni,
      As and Cr in the some sampling sites were higher than sediment quality guideline
      implying adverse impacts of these metals. Based on potential ecological risk
      (PER), the Chabahar Bay had low ecological risk. 

PMID- 27038882
TI  - Impacts of a high-discharge submarine sewage outfall on water quality in the
      coastal zone of Salvador (Bahia, Brazil).
AB  - Carbon and nitrogen stable isotopic signatures of suspended particulate organic
      matter and seawater biological oxygen demand (BOD) were measured along a coastal
      transect during summer 2015 to investigate pollution impacts of a high-discharge
      submarine sewage outfall close to Salvador, Brazil. Impacts of untreated sewage
      discharge were evident at the outfall site by depleted delta(13)Corg and
      delta(15)N signatures and 4-fold increased BOD rates. Pollution effects of a
      sewage plume were detectable for more than 6km downstream from the outfall site,
      as seasonal wind- and tide-driven shelf hydrodynamics facilitated its advective
      transport into near-shore waters. There, sewage pollution was detectable at
      recreational beaches by depleted stable isotope signatures and elevated BOD rates
      at high tides, suggesting high bacterial activity and increased infection risk by
      human pathogens. These findings indicate the urgent necessity for appropriate
      wastewater treatment in Salvador to achieve acceptable standards for released
      effluents and coastal zone water quality. 

PMID- 27038883
TI  - Reappraisal of GIP Pharmacology for Metabolic Diseases.
AB  - Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines
      for type 2 diabetes (T2D) and obesity due to their actions in lowering blood
      glucose and body weight. Despite similarities to GLP-1, glucose-dependent
      insulinotropic polypeptide (GIP) has not been extensively pursued as a medical
      treatment for T2D. This is largely based on observations of diminished responses
      of GIP to lower blood glucose in select patients, as well as evidence from rodent
      knockout models implying that GIP promotes obesity. These findings have prompted
      the belief in some, that inhibiting GIP action might be beneficial for metabolic
      diseases. However, a growing body of new evidence - including data based on
      refined genetically modified models and improved pharmacological agents -
      suggests a paradigm shift on how the GIP system should be manipulated for
      metabolic benefits.

PMID- 27038884
TI  - IL-17A induces chromatin remodeling promoting IL-8 release in bronchial
      epithelial cells: Effect of Tiotropium.
AB  - AIMS: IL-17A plays a key role in the persistence of airway inflammation,
      oxidative stress, and reduction of steroid-sensitivity in COPD. We studied the
      effect of IL-17A on chromatin remodeling and IL-8 production. MAIN METHODS: We
      measured the levels of IL-8 and IL-17A in induced sputum supernatants (ISS) from
      healthy controls (HCs), healthy smokers (HSs), and COPD patients by enzyme-linked
      immunosorbent assay (ELISA). A human bronchial epithelial cell line (16HBE) was
      stimulated with ISS from HCs, HSs, or COPD subjects. IL-8 was evaluated in 16HBE
      by Western blot and real-time polymerase chain reaction (PCR). Histone
      deacetylase 2 (HDAC2), acetyl histone H3 (Ac-His H3) (k9) and inhibitor kappa
      kinase alpha (IKKalpha) levels were evaluated in the nuclear extract by Western
      blot. Finally, we evaluated the effect of IL-17A depletion in ISS, the silencing
      of IKKalpha, and the anti-inflammatory effects of Tiotropium Spiriva(r) (100nM)
      on 16HBE. KEY FINDINGS: IL-8 and IL-17A levels were higher in ISS from COPD
      patients and HSs than from HCs. IL-8 protein and messenger RNA (mRNA) levels were
      increased in 16HBE stimulated with ISS from COPD patients compared with untreated
      cells. Furthermore, ISS from COPD patients reduced the nuclear levels of HDAC2
      while increasing the activity of both Ac-His H3 (k9) and IKKalpha in stimulated
      16HBE. IL-17A depletion in ISS and the IKKalpha silencing in 16HBE significantly
      increased the nuclear levels of HDAC2, reduced Ac-His H3 (k9), and promoted IL-8
      synthesis in stimulated 16HBE. Tiotropium controls the proinflammatory activity
      generated by ISS from COPD patients in 16HBE. SIGNIFICANCE: IL-17A present in the
      airway of COPD patients, which induces chromatin remodeling, promotes the release
      of IL-8 in the bronchial epithelium. Tiotropium is able to control this
      proinflammatory activity.

PMID- 27038885
TI  - Artificial olfactory system with fault-tolerant sensor array.
AB  - Numerous applications of artificial olfaction resulting from research in many
      branches of sciences have caused considerable interest in the enhancement of
      these systems. In this paper, we offer an architecture which is suitable for
      critical applications, such as medical diagnosis, where reliability and precision
      are deemed important. The proposed architecture is able to tolerate failures in
      the sensors of the array. In this study, the discriminating ability of the
      proposed architecture in detecting complex odors, as well as the performance of
      the proposed architecture in encountering sensor failure, were investigated and
      compared with the generic architecture. The results demonstrated that by applying
      the proposed architecture in the artificial olfactory system, the performance of
      system in the healthy mode was identical to the classic structure. However, in
      the faulty situation, the proposed architecture implied high identification
      ability of odor samples, while the generic architecture showed very poor
      performance in the same situation. Based on the results, it was possible to
      achieve high odor identification through the developed artificial olfactory
      system using the proposed architecture. 

PMID- 27038886
TI  - Optimal disturbance rejection for PI controller with constraints on relative
      delay margin.
AB  - Performance optimization with robustness constraints is frequently encountered in
      process control. Motivated by the analytical difficulties in dealing with the
      conventional robustness index, e.g., maximum sensitivity, we introduce the
      relative delay margin as a good alternative, which gives much simpler robust
      analysis. This point is illustrated by designing an optimal PI controller for the
      first-order-plus-dead-time (FOPDT) model. It is first shown that the PI
      controller parameters can be analytically derived in terms of a new pair of
      parameters, i.e., the phase margin and gain crossover frequency. The stability
      region of PI controller is subsequently obtained with a much simpler procedure
      than the existing approaches. It is further shown that a certain relative delay
      margin can represent the robustness level well and the contour can be sketched
      with a simpler procedure than the one using maximum sensitivity index. With
      constraints on the relative delay margin, an optimal disturbance rejection
      problem is then formulated and analytically solved. Simulation results show that
      the performance of the proposed methodology is better than that of other PI
      tuning rules. In this paper, the relative delay margin is shown as a promising
      robustness measure to the analysis and design of other advanced controllers. 

PMID- 27038887
TI  - Induction machine bearing faults detection based on a multi-dimensional MUSIC
      algorithm and maximum likelihood estimation.
AB  - Condition monitoring of electric drives is of paramount importance since it
      contributes to enhance the system reliability and availability. Moreover, the
      knowledge about the fault mode behavior is extremely important in order to
      improve system protection and fault-tolerant control. Fault detection and
      diagnosis in squirrel cage induction machines based on motor current signature
      analysis (MCSA) has been widely investigated. Several high resolution spectral
      estimation techniques have been developed and used to detect induction machine
      abnormal operating conditions. This paper focuses on the application of MCSA for
      the detection of abnormal mechanical conditions that may lead to induction
      machines failure. In fact, this paper is devoted to the detection of single-point
      defects in bearings based on parametric spectral estimation. A multi-dimensional
      MUSIC (MD MUSIC) algorithm has been developed for bearing faults detection based
      on bearing faults characteristic frequencies. This method has been used to
      estimate the fundamental frequency and the fault related frequency. Then, an
      amplitude estimator of the fault characteristic frequencies has been proposed and
      fault indicator has been derived for fault severity measurement. The proposed
      bearing faults detection approach is assessed using simulated stator currents
      data, issued from a coupled electromagnetic circuits approach for air-gap
      eccentricity emulating bearing faults. Then, experimental data are used for
      validation purposes. 

PMID- 27038888
TI  - Soluble form of the receptor for advanced glycation end-products attenuates
      inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung
      injury.
AB  - Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused
      by acute lung inflammation. Recently, the receptor for advanced glycation end
      products (RAGE) has attracted attention in the lung inflammatory response.
      However, the function of soluble form of RAGE (sRAGE), which is composed of an
      extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated
      the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human
      sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung
      inflammation. Our result revealed that RAGE was highly expressed on the alveolar
      type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45
      kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space
      was increased, whereas the expression of RAGE was decreased with alveolar
      disruption. Treatment of the injured lung with rsRAGE significantly suppressed
      the lung edema, the neutrophils infiltration, the release of high mobility group
      box-1 (HMGB1), and the expressions of TNF-alpha, IL-1beta and iNOS. These results
      suggest that the alveolar release of sRAGE may play a protective role against
      HMGB1 as well as exogenous pathogen-associated molecular patterns. Supplementary
      therapy with sRAGE may be an effective therapeutic strategy for ARDS. 

PMID- 27038889
TI  - Marine protected areas increase resilience among coral reef communities.
AB  - With marine biodiversity declining globally at accelerating rates, maximising the
      effectiveness of conservation has become a key goal for local, national and
      international regulators. Marine protected areas (MPAs) have been widely
      advocated for conserving and managing marine biodiversity yet, despite extensive
      research, their benefits for conserving non-target species and wider ecosystem
      functions remain unclear. Here, we demonstrate that MPAs can increase the
      resilience of coral reef communities to natural disturbances, including coral
      bleaching, coral diseases, Acanthaster planci outbreaks and storms. Using a 20
      year time series from Australia's Great Barrier Reef, we show that within MPAs,
      (1) reef community composition was 21-38% more stable; (2) the magnitude of
      disturbance impacts was 30% lower and (3) subsequent recovery was 20% faster that
      in adjacent unprotected habitats. Our results demonstrate that MPAs can increase
      the resilience of marine communities to natural disturbance possibly through
      herbivory, trophic cascades and portfolio effects. 

PMID- 27038890
TI  - Comparing Glaucomatous Disc Change Using Stereo Disc Viewing and the
      MatchedFlicker Software Program in Ophthalmologists-in-Training.
AB  - PURPOSE: To compare the accuracy and speed of using the computerized
      MatchedFlicker software program (EyeIC Inc, Narberth, Pennsylvania, USA) to
      evaluate glaucomatous optic disc change against the traditional gold standard of
      manually examining stereoscopic disc photographs. DESIGN: A prospective
      evaluation of diagnostic technology. METHODS: Two resident ophthalmologists and 1
      glaucoma fellow at the University of Florida independently evaluated 140 image
      pairs from 100 glaucomatous/ocular hypertensive patient eyes using a handheld
      stereo viewer and the MatchedFlicker program. Fifty had progression to glaucoma
      as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc
      Reading Group and the OHTS Endpoint Committee in the OHTS, and 50 more had
      photographs taken a few minutes apart, which were negative controls with no
      progression. Twenty photograph pairs from each group were duplicated to determine
      reviewer variability. Photographs were examined in alternating blocks of 70
      photograph pairs for each method, with the starting viewing method randomized.
      Reviewer accuracy and time to review for each method were measured. RESULTS:
      Using the handheld stereo viewer, the reviewers correctly identified progression
      or nonprogression in 76.0% of the slide pairs. Using the MatchedFlicker software,
      87.6% were correctly identified (P = .011). Evaluator speed averaged 34.1 seconds
      per image pair with the stereo viewer vs 24.9 seconds with the MatchedFlicker
      program (P = .044). Overall, Flicker was significantly more specific but less
      sensitive than stereo slides. Trainees appeared more reluctant to identify
      glaucoma progression from slides than from Flicker. For the 2 less experienced
      trainees Flicker was significantly more accurate. CONCLUSION: The MatchedFlicker
      software had a greater accuracy and was quicker to perform than using a handheld
      stereoscopic viewer.

PMID- 27038891
TI  - Scrolling Characteristics of Pre-Descemet Endothelial Keratoplasty Tissue: An Ex
      Vivo Study.
AB  - PURPOSE: To evaluate the scrolling propensity of pre-Descemet endothelial
      keratoplasty (PDEK) tissue and to compare it with each component of the PDEK
      tissue, namely the pre-Descemet layer (Dua's layer [PDL]) and the Descemet
      membrane (DM). DESIGN: Experimental laboratory investigation. METHODS: Fourteen
      human donor sclerocorneal discs in which a type 1 big bubble was obtained by
      stromal injection of air were studied. The wall of the type 1 big bubble was
      excised and its grade of scrolling noted. The components of the wall (ie, the DM
      and PDL) were then separated and the scrolling of each was individually graded.
      Statistical comparison of the grade of scrolling of each layer and correlation
      with age was carried out; 25-MUm slices of anterior and posterior stroma obtained
      with the femtosecond laser from 4 control samples were used for comparison. The
      main outcome measure was the grade of scrolling of PDEK tissue in comparison with
      PDL and DM. RESULTS: Mean donor age was 67 years. The mean grade of the scroll
      formed by PDEK tissue was1.6 compared to 0.64 for PDL alone and 3.6 for DM alone.
      The difference was statistically significant. No correlation between donor age
      and degree of scrolling for any of the tissues tested was found. CONCLUSION: PDEK
      tissue scrolls less than DM. PDL scrolls the least. This demonstrates that PDL
      tissue splints the DM and reduces its scrolling in PDEK. This feature has
      relevance to tissue preparation, handling, and unscrolling in the eye during
      endothelial keratoplasty.

PMID- 27038892
TI  - Outer Retinal Structural Alternation and Segmentation Errors in Optical Coherence
      Tomography Imaging in Patients With a History of Retinopathy of Prematurity.
AB  - PURPOSE: To evaluate retinal anatomy and segmentation errors from spectral-domain
      optical coherence tomography (SD-OCT) imaging in school-aged children. DESIGN: A
      prospective cohort study in a referral medical center. METHODS: One hundred
      thirty-three eyes of 133 patients were enrolled. Patients were grouped as those
      who were treated for retinopathy of prematurity (ROP) (ROP-Tx group); those with
      spontaneously regressed ROP (ROP-non-Tx group); other premature patients
      (premature group); and full-term age-matched children (full-term group). Anatomy
      and segmentation errors of retina were evaluated by SD-OCT. RESULTS: The mean age
      at assessment was 9.5 years (range, 4-16 years). The external limiting membrane
      (ELM) and the cone outer segment tips (COST) line were least frequently
      identified in patients of the ROP-Tx group (65.2% and 47.8%, P = .002 and P <
      .001, respectively). The visual acuity of the patients did not correlate
      significantly with the absence of COST line (P = .140) but correlated with the
      absence of ELM (P < .001). The presence of artifacts, including misidentification
      of the inner retina, misidentification of the outer retina, out-of-register
      artifacts, off-center scans, and degraded scan images, was observed to range from
      0.6% to 50.0% in 4 groups of patients. All types of errors occurred more
      frequently in the ROP-Tx group than in the full-term group (all P < .05).
      CONCLUSIONS: Outer retinal abnormalities were commonly observed in the ROP-Tx
      group. The higher segmentation errors in the ROP-Tx group might be related to
      fine structural abnormalities in the outer retina. Future studies are needed to
      investigate the mechanisms for these structural changes.

PMID- 27038893
TI  - Quantitative Optical Coherence Tomography Angiography Features and Visual
      Function in Eyes With Branch Retinal Vein Occlusion.
AB  - PURPOSE: To measure the vascular density and foveal avascular zone (FAZ) area in
      the deep and superficial retinal vascular networks using optical coherence
      tomography angiography (OCTA) in patients with branch retinal vein occlusion
      (BRVO). DESIGN: Retrospective observational case series. METHODS: Patients with
      unilateral BRVO involving the macula were enrolled. OCTA was performed on the
      BRVO and fellow eyes. Macular vascular density, FAZ area, and foveal thickness
      were measured in all eyes. RESULTS: Seventeen eyes of 17 patients met inclusion
      criteria. The mean overall vascular density measured in the entire scan was lower
      in BRVO eyes compared to fellow eyes in both the superficial (48.07% vs 52.60%,
      respectively; P < .001) and deep (52.60% vs 57.67%, respectively; P < .001)
      networks. In both networks, the density was lower in the affected BRVO sector
      compared to the unaffected sector in the same eye and in the fellow eye (P <
      .001). In the deep network, the density was lower in the unaffected sector of the
      BRVO eye compared with the corresponding sector in the fellow eye (58.87% vs
      61.65%, respectively; P = .04). A negative correlation was found between the
      logarithm of the minimal angle of resolution (logMAR) visual acuity and the
      overall density in superficial (r = -0.40, P = .02) and deep (r = -0.38, P = .03)
      networks. The mean FAZ area in BRVO eyes was significantly lower only at the
      level of the deep network when compared to the fellow eyes (0.519 mm(2) vs 0.410
      mm(2), respectively; P = .02) and correlated positively with logMAR (r = 0.34, P
      = .04). CONCLUSION: In eyes with BRVO, quantitative OCTA measurements confirm
      decreased vascular density in both the superficial and deep vascular networks.
      Moreover, vascular density and FAZ area appear to correlate with visual function.

PMID- 27038894
TI  - Changes in Anterior Segment Morphology After Laser Peripheral Iridotomy in Acute
      Primary Angle Closure.
AB  - PURPOSE: To evaluate the anterior segment biometric changes measured by anterior
      segment optical coherence tomography (AS-OCT) in acute primary angle closure
      (APAC) after laser peripheral iridotomy (LPI). DESIGN: Prospective interventional
      study. METHODS: In this clinic-based study, 52 eyes of 52 patients with resolved
      APAC attack who underwent LPI were enrolled. Subjects underwent complete
      ophthalmic examination and AS-OCT imaging before and 6 weeks after LPI. Anterior
      chamber depth (ACD), anterior chamber area (ACA), iris thickness (IT), iris area,
      iris curvature, lens vault (LV), anterior vault, angle opening distance (AOD500,
      AOD750), and trabecular iris space area (TISA500, TISA750) were measured in
      qualified images and compared before and after LPI. A linear mixed-model analysis
      was performed for potential predictors of change in AOD750. Main outcome measure
      was change in AOD750 after LPI. RESULTS: The mean age of participants was 60.7 +/
      9.2 years. Mean angle width (Shaffer grade) changed from 0.25 +/- 0.34 at
      baseline to 1.22 +/- 0.86 after LPI (P < .001). However, 25 nasal angles (48.0%)
      and 28 temporal angles (53%) had iridotrabecular contact after LPI. All angle
      parameters (AOD500, AOD750, TISA500, TISA750; P <= .03), ACD (P = .001), and ACA
      (P < .001) increased significantly after LPI. Iris curvature and LV were reduced
      (P = .01 for both) after LPI, but there was no significant change in IT and iris
      area. After multivariate analysis, pre-LPI AOD750 was the only factor associated
      with change in AOD750 (beta = -0.992, P = .02). Exaggerated LV, defined as LV
      greater than one-third of the anterior vault (sum of LV and ACD), was present in
      61.5% of the cases (32 eyes). The extent of change in angle parameters was not
      significantly different between groups with and without exaggerated LV after LPI.
      CONCLUSION: This study confirms that LPI results in a significant increase in the
      angle width, ACD, and ACA as well as flattening of the iris in APAC eyes. The
      extent of angle deepening is inversely related to baseline angle width. The lens
      shifts posteriorly after resolution of attack, especially in those with greater
      lens vault.

PMID- 27038895
TI  - Orbital Inflammation in Pregnant Women.
AB  - OBJECTIVE: To analyze overlaps between pregnancy and orbital inflammation (OI).
      DESIGN: Retrospective observational case series. METHODS: Eight new cases from
      1997 to 2015 and 2 previously published cases were identified for inclusion in
      this investigation to provide the fullest clinical picture. Medical records,
      imaging studies, and the results of biopsies were reviewed. RESULTS: Three
      categories of association were discovered: (1) OI arising for the first time
      during pregnancy (5 cases); (2) OI arising within 3 months of delivery (2 cases);
      and (3) previously diagnosed OI reactivated or exacerbated by pregnancy (3
      cases). One patient had a preexistent systemic autoimmune disease and another's
      was later diagnosed. One patient had attacks during sequential pregnancies.
      Findings included eyelid swelling and erythema, conjunctival chemosis, pain on
      eye movement, minimal diplopia, the usual absence of proptosis, and general
      preservation of visual acuity. Imaging studies disclosed extraocular muscle
      swelling (8 cases), most frequently of a single lateral rectus muscle. There were
      2 cases of dacryoadenitis; 1 of these and an additional case displayed
      inflammation of the retrobulbar fat. Corticosteroids effected resolution of most
      symptoms. Singleton births were normal with the exceptions of an intrauterine
      fetal demise owing to acrania and a molar pregnancy. CONCLUSION: OI usually
      affects a single rectus muscle (typically the lateral) and, less often, the
      lacrimal gland and is often mild when it arises during or after pregnancy.
      Independent systemic autoimmune disease is an uncommon feature. Corticosteroids
      were efficacious except in 1 case with severe orbital scarring. No definitive
      causal relationships between pregnancy and OI could be established based on the
      clinical data.

PMID- 27038896
TI  - Influence of purified multiwalled carbon nanotubes on the mechanical and
      morphological behavior in poly (L-lactic acid) matrix.
AB  - Poly (L-latic acid) (PLLA) is a bioresorbable polymer widely used as a
      biomaterial, but its fragility can limit its use. An alternative is to produce
      polymer nanocomposites, which can enhance the mechanical properties of polymeric
      matrix, resulting in a material with differentiated properties. In this work,
      PLLA based nanocomposites containing 0.25, 0.5 and 1.0wt% of purified multiwalled
      carbon nanotubes (p-MWCNTs) were prepared by the solvent casting method. The
      morphology and mechanical properties results show an improvement in strain at
      break for 0.25 and 0.5wt% p-MWCNTs and an increase in stiffness and elastic
      modulus for all compositions. Nanocomposites presented a p-MWCNTs agglomeration;
      however, there was a good stress transfer between PLLA and p-MWCNTs, which was
      confirmed by the increase in the hardness and elastic modulus. Atomic force
      microscopy analysis indicated an increase in roughness after nanotube addition.
      The in vitro biological study showed that PLLA/p-MWCNTs nanocomposites are
      cytocompatible with osteoblasts cells. The capacity of PLLA nanocomposites to
      stimulate osteogenesis was investigated by alkaline phosphatase (ALP) activity
      assay. Higher ALP activity was found on osteoblasts cultured on nanocomposites
      with 0.25 and 0.5wt% p-MWCNT compared to neat PLLA, confirming that PLLA
      cytocompatibility was improved on these compositions. Finally, our results showed
      that by a simple and inexpensive solvent casting method, it is possible to
      manufacture biofunctional nanocomposites devices with potential for orthopedic
      applications.

PMID- 27038897
TI  - Reproducibility of Illumina platform deep sequencing errors allows accurate
      determination of DNA barcodes in cells.
AB  - BACKGROUND: Next generation sequencing (NGS) of amplified DNA is a powerful tool
      to describe genetic heterogeneity within cell populations that can both be used
      to investigate the clonal structure of cell populations and to perform genetic
      lineage tracing. For applications in which both abundant and rare sequences are
      biologically relevant, the relatively high error rate of NGS techniques
      complicates data analysis, as it is difficult to distinguish rare true sequences
      from spurious sequences that are generated by PCR or sequencing errors. This
      issue, for instance, applies to cellular barcoding strategies that aim to follow
      the amount and type of offspring of single cells, by supplying these with unique
      heritable DNA tags. RESULTS: Here, we use genetic barcoding data from the
      Illumina HiSeq platform to show that straightforward read threshold-based
      filtering of data is typically insufficient to filter out spurious barcodes.
      Importantly, we demonstrate that specific sequencing errors occur at an
      approximately constant rate across different samples that are sequenced in
      parallel. We exploit this observation by developing a novel approach to filter
      out spurious sequences. CONCLUSIONS: Application of our new method demonstrates
      its value in the identification of true sequences amongst spurious sequences in
      biological data sets.

PMID- 27038898
TI  - Prevalence of smear positive pulmonary tuberculosis and associated risk factors
      among prisoners in Hadiya Zone prison, Southern Ethiopia.
AB  - BACKGROUND: People concentrated in congregated systems such as prisons, are
      important but often neglected reservoirs for tuberculosis transmission, and
      threaten those in the outside community. The condition is more serious in Africa
      particularly in Sub-Saharan Africa (SSA) due to its poor living conditions and
      ineffective health services. OBJECTIVES: This study was conducted to determine
      the prevalence of smear positive pulmonary tuberculosis and associated risk
      factors among prisoners in Hadiya Zone prison. METHODS: A cross-sectional survey
      was carried out from May to June 2013 in Hadiya Zone prison. Prison inmates who
      had history of cough for at least a week were included in the study. Three
      morning sputum samples were collected from suspected inmates and examined through
      compound light microscopy. The data obtained was analyzed using statistical
      software like Epidata and STATA. RESULTS: A total of 164 prisoners were included
      in the survey using active screening strategy and the point prevalence of smear
      positive pulmonary tuberculosis (PTB) in the prison was 349.2 per 100,000
      populations; about three times higher than its prevalence in the general
      population. Even though lack of visit from family was the only variable
      identified as a risk factor for PTB (P = 0.029), almost all of the PTB positive
      cases were rural residents, farmers, male youngsters and those who shared cell
      with TB patients and chronically coughing persons as well as those who stayed in
      a cell that contains >100 inmates. CONCLUSION: There is high prevalence of TB in
      Hadiya Zone prison with possible active transmission of TB within the prison. The
      study also documented a number of factors which may facilitate exposures to TB
      though most of them are not significantly associated. Therefore, strong
      cooperation between prison authorities and the national tuberculosis control
      programmes is urgently required to develop locally appropriate interventions to
      reduce transmission.

PMID- 27038899
TI  - Equations for water-triolein partition coefficients for neutral species;
      comparison with other water-solvent partitions, and environmental and
      toxicological processes.
AB  - Linear free energy relationships, LFERs, have been constructed for water-triolein
      partition coefficients for neutral species. It is shown that separate equations
      are required for wet and dry triolein. From a comparison of the equation
      coefficients for water-wet triolein with those for 52 other water-solvent systems
      it is shown that there is little correspondence between triolein and any of the
      52 other solvents - only the water-isopropyl myristate system is close to the
      water-wet triolen system. A comparison of equation coefficients for the water-wet
      triolein system with LFER coefficients of 16 environmentally important processes
      shows that wet triolein is not a suitable model for any of the processes,
      although a number of other water-solvent systems are possible models for some of
      the environmental processes. A comparison of LFER coefficients with those of 17
      aqueous toxicological processes reveals that most of the water-solvent systems,
      including water-wet triolein, will be poor models for any of the toxicological
      systems, but the water-lower alcohol systems show promise as models for a number
      of the toxicological systems. Our method of comparison of coefficients for LFERs
      that have exactly the same independent variables can be extended to various other
      types of system. 

PMID- 27038900
TI  - Soil radioactivity levels, radiological maps and risk assessment for the state of
      Kuwait.
AB  - An evaluation of the radioactivity levels associated with naturally occurring
      radioactive materials has been undertaken as part of a systematic study to
      provide a surface radiological map of the State of Kuwait. Soil samples from
      across Kuwait were collected, measured and analysed in the current work. These
      evaluations provided soil activity concentration levels for primordial
      radionuclides, specifically members of the (238)U and (232)Th decay chains and
      (40)K which. The (238)U and (232)Th chain radionuclides and (40)K activity
      concentration values ranged between 5.9 <-> 32.3, 3.5 <-> 27.3, and 74 <-> 698
      Bq/kg respectively. The evaluated average specific activity concentrations of
      (238)U, (232)Th and (40)K across all of the soil samples have mean values of 18,
      15 and 385 Bq/kg respectively, all falling below the worldwide mean values of 35,
      40 and 400 Bq/kg respectively. The radiological risk factors are associated with
      a mean of 33.16 +/- 2.46 nG/h and 68.5 +/- 5.09 Bq/kg for the external dose rate
      and Radium equivalent respectively. The measured annual dose rates for all
      samples gives rise to a mean value of 40.8 +/- 3.0 MUSv/y while the internal and
      internal hazard indices have been found to be 0.23 +/- 0.02 and 0.19 +/- 0.01
      respectively. 

PMID- 27038901
TI  - Multiple model approach to evaluation of accelerated carbonation for steelmaking
      slag in a slurry reactor.
AB  - Basic oxygen furnace slag (BOFS) exhibits highly alkaline properties due to its
      high calcium content, which is beneficial to carbonation reaction. In this study,
      accelerated carbonation of BOFS was evaluated under different reaction times,
      temperatures, and liquid-to-solid (L/S) ratios in a slurry reactor. CO2 mass
      balance within the slurry reactor was carried out to validate the technical
      feasibility of fixing gaseous CO2 into solid precipitates. After that, a multiple
      model approach, i.e., theoretical kinetics and empirical surface model, for
      carbonation reaction was presented to determine the maximal carbonation
      conversion of BOFS in a slurry reactor. On one hand, the reaction kinetics of
      BOFS carbonation was evaluated by the shrinking core model (SCM). Calcite (CaCO3)
      was identified as a reaction product through the scanning electronic microscopy
      and X-ray diffraction analyses, which provided the rationale of applying the SCM
      in this study. The rate-limiting step of carbonation was found to be ash
      diffusion controlled, and the effective diffusivity for carbonation of BOFS in a
      slurry reactor were determined accordingly. On the other hand, the carbonation
      conversion of BOFS was predicted by the response surface methodology (RSM) via a
      nonlinear mathematical programming. According to the experimental data, the
      highest carbonation conversion of BOFS achieved was 57% under an L/S ratio of 20
      mL g(-1), a CO2 flow rate of 0.1 L min(-1), and a pressure of 101.3 kPa at 50 
      degrees C for 120 min. Furthermore, the applications and limitations of SCM and
      RSM were examined and exemplified by the carbonation of steelmaking slags. 

PMID- 27038903
TI  - Evaluation of background soil and air polychlorinated biphenyl (PCB)
      concentrations on a hill at the outskirts of a metropolitan city.
AB  - Air and soil sampling was conducted inside a forested area for 22 months. The
      sampling location is situated to the north of a metropolitan city. Average
      atmospheric gas and particle concentrations were found to be 180 and 28 pg m(-3)
      respectively, while that of soil phase was detected to be 3.2 ng g(-1) on dry
      matter, The congener pairs of PCB#4-10 had the highest contribution to each
      medium. TEQ concentration was 0.10 pg m(-3), 0.07 pg m(-3), 21.92 pg g(-1), for
      gas, particle and soil phases, respectively. PCB#126 and PCB#169 contributed to
      over 99% of the entire TEQ concentrations for each medium. Local sources were
      investigated by conditional probability function (CPF) and soil/air fugacity.
      Landfilling area and medical waste incinerator, located to the 8 km northeast,
      contributed to ambient concentrations, especially in terms of dioxin-like
      congeners. The industrial settlement (called Dilovasi being to the east southeast
      of 60 km distant) contributed from southeast direction. Further sources were
      identified by potential source contribution function (PSCF). Sources at close
      proximity had high contribution. Air mass transportation from Aliaga industrial
      region (being to the southwest of 300 km distant) moderately contributed to
      ambient concentrations. Low molecular weight congeners were released from soil
      body. 5-CBs and 6-CBs were close to equilibrium state between soil/air
      interfaces. PCB#171 was close to equilibrium and PCB#180 was likely to evaporate
      from soil, which constitute 7-CBs. PCB#199, representing 8-CBs deposited to soil.
      9-CB (PCB#207) was in equilibrium between soil and air phases. 

PMID- 27038902
TI  - Perfluorinated alkyl acids in the plasma of South African crocodiles (Crocodylus
      niloticus).
AB  - Perfluorinated alkyl acids (PFAAs) are environmental contaminants that have been
      used in many products for over 50 years. Interest and concern has grown since
      2000 on the widespread presence of PFAAs, when it was discovered that PFAAs were
      present in wildlife samples around the northern hemisphere. Since then, several
      studies have reported PFAAs in wildlife from many locations, including the remote
      regions of Antarctica and the Arctic. Although there are a multitude of studies,
      few have reported PFAA concentrations in reptiles and wildlife in the Southern
      Hemisphere. This study investigated the presence of PFAAs in the plasma of Nile
      crocodiles (Crocodylus niloticus) from South Africa. Crocodiles were captured
      from five sites in and around the Kruger National Park, South Africa, and plasma
      samples examined for PFAAs. Perfluorooctane sulfonate (PFOS) was the most
      frequent PFAA detected; with median values of 13.5 ng/g wet mass in crocodiles.
      In addition to PFOS, long chain perfluorinated carboxylic acids were also
      detected. Correlations between total length and PFAA load were investigated, as
      were differences in PFAA accumulation between sexes. No correlations were seen
      between crocodile size, nor were there sex-related differences. Spatial
      differences were examined and significant differences were observed in samples
      collected from the different sites (p < 0.05). Flag Boshielo Dam had the highest
      PFOS measurements, with a median concentration of 50.3 ng/g wet mass, when
      compared to the other sites (median concentrations at other sites below 14.0 ng/g
      wet mass). This suggests a point source of PFOS in this area. 

PMID- 27038904
TI  - The joint effects of arsenic and risk diplotypes of insulin-like growth factor
      binding protein-3 in renal cell carcinoma.
AB  - The association between renal cell carcinoma (RCC) and diabetes mellitus (DM),
      alcohol consumption, insulin-like growth factor binding protein-3 (IGFBP-3) gene,
      and arsenic exposure, has been the subject of independent studies. However, few
      studies have examined the combined effect of these factors on RCC risk. The aim
      of this study was to examine the association between these risk factors and the
      odds ratio (OR) of RCC. A hospital-based case-control study was conducted in 398
      RCC patients and 756 age- and gender-matched non-cancer controls. Genomic DNA was
      used to examine the genotype of IRS-1 (Gly972Arg), PI3-K (Met362Ile), IGFBP-3 (A[
      202]C), and IGFBP-3 (C[-1590]A) by PCR-RFLP. Profiles of urinary arsenic were
      measured by high performance liquid chromatography linked with hydride generator
      and atomic absorption spectrometry. Participants who had never consumed alcohol
      and who had high total levels of urinary arsenic and DM had a high OR of RCC.
      IGFBP-3 (A[-202]C) and IGFBP-3 (C[-1590]A) were in linkage disequilibrium.
      Participants carrying high-risk IGFBP-3 diplotypes A-C/C-C, A-A/A-C, and C-A/C-A
      had a significantly higher odds ratio (OR) and 95% confidence interval (2.80,
      1.91-4.12) of RCC compared to those carrying other IGFBP-3 diplotypes. This is
      the first study to show that borderline significant interaction of high total
      levels of urinary arsenic and IGFBP-3 high-risk diplotypes significantly enhanced
      the OR of RCC. Our data also provide evidence that subjects with more risk
      factors (e.g., high total levels of urinary arsenic, never consumed alcohol,
      IGFBP-3 high-risk diplotypes) may experience a higher OR of RCC. 

PMID- 27038905
TI  - Processes influencing chemical biomagnification and trophic magnification factors
      in aquatic ecosystems: Implications for chemical hazard and risk assessment.
AB  - Bioconcentration factors (BCFs) and bioaccumulation factors (BAFs) are widely
      used in scientific and regulatory programs to assess chemical hazards. There is
      increasing interest in also using biomagnification factors (BMFs) and trophic
      magnification factors (TMFs) for this purpose, especially for highly hydrophobic
      substances that may reach high concentrations in predatory species that occupy
      high trophic level positions in ecosystems. Measurements of TMFs in specific
      ecosystems can provide invaluable confirmation that biomagnification or
      biodilution has occurred across food webs, but their use in a regulatory context
      can be controversial because of uncertainties related to the reliability of
      measurements and their regulatory interpretation. The objective of this study is
      to explore some of the recognized uncertainties and dependencies in field BMFs
      and TMFs. This is accomplished by compiling a set of three simple food web models
      (pelagic, demersal and combined pelagic-demersal) consisting of up to seven
      species to simulate field BMFs and TMFs and to explore their dependences on
      hydrophobicity (expressed as log KOW), rates of biotransformation and growth,
      sediment-water fugacity ratios, and extent of food web omnivory and issues that
      arise when chemical concentration gradients exist in aquatic ecosystems. It is
      shown that empirical TMFs can be highly sensitive to these factors, thus the use
      of TMFs in a regulatory context must recognize these sensitivities. It is
      suggested that simple but realistic evaluative food web models could be used to
      extend BCF and BAF assessments to include BMFs and TMFs, thus providing a tool to
      address bioaccumulation hazard and the potential risk of exposures to elevated
      chemical concentrations in organisms at high trophic levels. 

PMID- 27038907
TI  - [Social inequalities in health less pronounced in women than in men: A question
      of measurements?].
AB  - Social inequalities in mortality are generally less pronounced for women than for
      men. Are women's health risks and behaviours more homogeneous, or does this
      pattern arise from a measurement issue inducing an under-estimation of these
      inequalities? This article reviews a number of studies covering different
      dimensions of health and different dimensions of social status. Their findings
      show that there are large social inequalities in health among women. The focus on
      the working careers, family histories and conciliation of multiple activities
      provides evidence of major social determinants of health to which women are
      widely exposed. This article highlights the need to broaden the notion of social
      inequality and to redefine the social categories, notably by considering the
      distinct trajectories of men and women and their different spheres of activity.
      It highlights that gender differences in health are themselves partly socially
      constructed, as suggested by the gender approaches in the social sciences.

PMID- 27038906
TI  - Pioglitazone ameliorates the phenotype of a novel Parkinson's disease mouse model
      by reducing neuroinflammation.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      characterized by motor and non-motor symptoms. The cause of the motor symptoms is
      the loss of dopaminergic neurons in the substantia nigra with consequent
      depletion of dopamine in the striatum. Although the etiology of PD is unknown,
      mitochondrial dysfunctions, including cytochrome c oxidase (Complex IV)
      impairment in dopaminergic neurons, have been associated with the disease's
      pathophysiology. In order to analyze the role of Complex IV in PD, we knocked out
      Cox10 (essential for the maturation of COXI, a catalytic subunit of Complex IV)
      in dopaminergic neurons. We also tested whether the resulting phenotype was
      improved by stimulating the PPAR-gamma pathway. RESULTS: Cox10/DAT-cre mice
      showed decreased numbers of TH+ and DAT+ cells in the substantia nigra, early
      striatal dopamine depletion, motor defects reversible with L-DOPA treatment and
      hypersensitivity to L-DOPA with hyperkinetic behavior. We found that chronic
      pioglitazone (PPAR-gamma agonist) treatment ameliorated the motor phenotype in
      Cox10/DAT-cre mice. Although neither mitochondrial function nor the number of
      dopaminergic neurons was improved, neuroinflammation in the midbrain and the
      striatum was decreased. CONCLUSIONS: By triggering a mitochondrial Complex IV
      defect in dopaminergic neurons, we created a new mouse model resembling the late
      stages of PD with massive degeneration of dopaminergic neurons and striatal
      dopamine depletion. The motor phenotypes were improved by Pioglitazone treatment,
      suggesting that targetable secondary pathways can influence the development of
      certain forms of PD.

PMID- 27038908
TI  - [Nutrition policies: What possible impacts on health inequalities?].

PMID- 27038909
TI  - DNA methylation within melatonin receptor 1A (MTNR1A) mediates paternally
      transmitted genetic variant effect on asthma plus rhinitis.
AB  - BACKGROUND: Asthma and allergic rhinitis (AR) are common allergic comorbidities
      with a strong genetic component in which epigenetic mechanisms might be involved.
      OBJECTIVE: We aimed to identify novel risk loci for asthma and AR while
      accounting for parent-of-origin effect. METHODS: We performed a series of genetic
      analyses, taking into account the parent-of-origin effect in families ascertained
      through asthma: (1) genome-wide linkage scan of asthma and AR in 615 European
      families, (2) association analysis with 1233 single nucleotide polymorphisms
      (SNPs) covering the significant linkage region in 162 French Epidemiological
      Study on the Genetics and Environment of Asthma families with replication in 154
      Canadian Saguenay-Lac-Saint-Jean asthma study families, and (3) association
      analysis of disease and significant SNPs with DNA methylation (DNAm) at CpG sites
      in 40 Saguenay-Lac-Saint-Jean asthma study families. RESULTS: We detected a
      significant paternal linkage of the 4q35 region to asthma and allergic rhinitis
      comorbidity (AAR; P = 7.2 * 10(-5)). Association analysis in this region showed
      strong evidence for the effect of the paternally inherited G allele of rs10009104
      on AAR (P = 1.1 * 10(-5), reaching the multiple-testing corrected threshold).
      This paternally inherited allele was also significantly associated with DNAm
      levels at the cg02303933 site (P = 1.7 * 10(-4)). Differential DNAm at this site
      was found to mediate the identified SNP-AAR association. CONCLUSION: By
      integrating genetic and epigenetic data, we identified that a differentially
      methylated CpG site within the melatonin receptor 1A (MTNR1A) gene mediates the
      effect of a paternally transmitted genetic variant on the comorbidity of asthma
      and AR. This study provides a novel insight into the role of epigenetic
      mechanisms in patients with allergic respiratory diseases.

PMID- 27038910
TI  - Understandings of spirituality and its role in illness recovery in persons with
      schizophrenia and mental-health professionals: a qualitative study.
AB  - BACKGROUND: Spirituality has received increased attention in the psychiatric
      literature; however, it remains underexplored on a global level. Knowledge about
      spirituality of persons with schizophrenia is often hampered by positive and
      negative symptoms, which limit their expression of spiritual needs and shift
      mental-health professionals' focus from spiritual care to symptom control.
      Differences in the ways that the two parties understand spirituality may create
      different expectations and further hinder the provision of high-quality holistic
      care. This study investigated the meaning and roles of spirituality from the
      perspectives of persons with schizophrenia and mental-health professionals.
      METHODS: A qualitative design with semi-structured individual interviews was
      adopted. The analysis was based on data collected from interviews with 18 clients
      diagnosed with schizophrenia and 19 mental-health professionals from public
      hospitals and mental-health community rehabilitation centres in Hong Kong. Data
      were collected and analysed based on grounded theory principles. RESULTS: Both
      clients and professionals regarded spirituality as an inherent part of a person's
      well-being, clients' rehabilitation, and their lives in general. At the personal
      level, the clients' descriptions were more factual, concrete, short term, and
      affective, whereas the professionals' descriptions were more abstract, complex,
      and cognitive. At the communal level, both parties had a similar understanding of
      spirituality but different interpretations of its role in recovery from mental
      illness. The clients regarded spirituality as a source of giving and receiving
      love and care, whereas the professionals regarded it as a means of receiving
      support and managing symptoms. CONCLUSIONS: Building a common understanding on
      the concept of spirituality and the significant role it plays in rehabilitation
      between clients and mental-health professionals is an essential first step to
      support clients' spiritual health. Clients tend to seek for stability, peace, and
      growth rather than an existential quest; while professionals hold a more
      pathological perspective, viewing spirituality as a means to relieve symptoms,
      increase social acceptance, and cope with illness experiences. The differential
      understanding of the two perspectives provides insight and perhaps a roadmap for
      developing spiritual assessments and holistic care in the psychiatric context.

PMID- 27038911
TI  - "I don't have options but to persevere." Experiences and practices of care for
      HIV and diabetes in rural Tanzania: a qualitative study of patients and family
      caregivers.
AB  - BACKGROUND: The high prevalence of chronic diseases in Tanzania is putting a
      strain on the already stretched health care services, patients and their
      families. This study sought to find out how health care for diabetes and HIV is
      perceived, practiced and experienced by patients and family caregivers, to inform
      strategies to improve continuity of care. METHODS: Thirty two in-depth interviews
      were conducted among 19 patients (10 HIV, 9 diabetes) and 13 family caregivers (6
      HIV, 7 diabetes). Diabetes patients and caregivers were accessed through one
      referral facility. HIV patients and caregivers were accessed through HIV clinics
      at the district hospital, one health centre and one dispensary respectively. The
      innovative care for chronic conditions framework informed the study design. Data
      was analysed with the help of Nvivo 10. RESULTS: Three major themes emerged;
      preparedness and practices in care, health care at health facilities and
      community support in care for HIV and diabetes. In preparedness and practices,
      HIV patients and caregivers knew more about aspects of HIV than did diabetes
      patients and caregivers on diabetes aspects. Continued education on care for the
      conditions was better structured for HIV than diabetes. On care at facilities,
      HIV and diabetes patients reported that they appreciated familiarity with
      providers, warm reception, gentle correction of mistakes and privacy during care.
      HIV services were free of charge at all levels. Costs involved in seeking
      services resulted in some diabetes patients to not keep appointments. There was
      limited community support for care of diabetes patients. Community support for
      HIV care was through community health workers, patient groups, and village
      leaders. CONCLUSION: Diabetes and HIV have socio-cultural and economic
      implications for patients and their families. The HIV programme is successfully
      using decentralization of health services, task shifting and CHWs to address
      these implications. For diabetes and NCDs, decentralization and task shifting are
      also important and, strengthening of community involvement is warranted for
      continuity of care and patient centeredness in care. While considering
      differences between HIV and diabetes, we have shown that Tanzania's rich
      experiences in community involvement in health can be leveraged for care and
      treatment of diabetes and other NCDs.

PMID- 27038912
TI  - Depleting extracellular vesicles from fetal bovine serum alters proliferation and
      differentiation of skeletal muscle cells in vitro.
AB  - BACKGROUND: Fetal bovine serum (FBS) contains a wide range of growth factors,
      hormones, vitamins, amino acids, fatty acids and trace elements required for cell
      growth. It was shown that animal sera contain also extracellular vesicles (EVs)
      with important biological properties; thus we wondered whether EVs present in FBS
      would influence muscle cell phenotype. EVs were removed from sera by
      ultracentrifugation (18 h). C2C12, L6 and human primary myoblasts, were grown
      either in classical media (CM) or in EVs-depleted media. Differentiation was
      induced by replacing the culture medium either with CM or EV-depleted media. qRT
      PCR of relevant genes and miRNA involved in proliferation, differentiation,
      energy metabolism and EVs formation and secretion were performed. RESULTS: Growth
      of myoblasts in EV-free media during proliferation produces the most unfavorable
      situation for proper myotube formation, when considering C212 and human
      myoblasts. Removing EVs from serum committed myoblasts to differentiate
      precociously (induction of myogenin and decreased expression of myomiR involved
      in myogenesis). C2C12 and human myoblasts, grown constantly in EV-depleted media
      during proliferation and differentiation, formed less myotubes than in CM. They
      had a reduced level of myogenin and a strong increase in myostatin expression, a
      negative regulator of muscle cell differentiation that affects myotube size. This
      situation was not reversed when confluent myoblasts were switched to CM for
      differentiation. Like C2C12 and human cells, L6 formed less myotubes in EVs
      depleted media. However, as they do not express myostatin, L6 myotubes were
      larger and expressed higher level of CKTM2 compared to myotubes grown in CM
      suggesting that they had reached a higher level of differentiation. CONCLUSIONS:
      Researchers studying the role of muscle EVs in culture conditions should consider
      that depleting EVs from serum alters the phenotype of muscle cells.
      Interestingly, the cross-talk between myoblasts and myotubes during myogenesis
      (Forterre 2014, PLoS One. 2014 Jan 2;9(1):e84153) can be recapitulate by using
      FBS-EVs as well. This implies that EVs can transfer specific signals to cells
      from unrelated species and that part of serum EV composition is evolutionarily
      conserved (e.g.; myomiR are detected in FBS-EVs). EVs in body fluids could have
      an unsuspected function during embryogenesis and in regulation of cellular
      processes such as hypertrophy and hyperplasia.

PMID- 27038913
TI  - Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III
      apparatus: An evaluation of the effect of systematic agitation and ionic
      strength.
AB  - The aim of the study was to evaluate the effect of systematic agitation,
      increasing ionic strength and gel strength on drug release from a gel-forming
      matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with
      theophylline as a model drug. The triboelectric charging; particle sizing, water
      content, true density and SEM of all the hypromellose grades, theophylline and
      formulated blends were characterised. The results showed that balanced inter
      particulate forces exist between drug particles and the excipient surface and
      this enabled optimum charge to mass ratio to be measured. Agitation and ionic
      strength affected drug release from E50LV and E4M tablet matrices in comparison
      to the E10M tablet matrices. Drug release increased substantially when water was
      used as the dissolution media relative to media at pH 1.2 (containing 0.4M NaCl).
      The results showed all f2 values for the E10M tablet matrices were above 50
      suggesting the drug release from these tablet matrices to be similar. Rheological
      data also explained the different drug release behaviour with the stress required
      to yield/erode being 1Pa, 150Pa, and 320Pa, for the E50LV, E4M and E10M
      respectively. The stiffness of the gel was also found to be varied from 2.5Pa,
      176.2Pa and 408.3Pa for the E50LV, E4M and E10M respectively. The lower G' value
      can be explained by a softer gel being formed after tablet introduction into the
      dissolution media thereby indicating faster drug release. 

PMID- 27038914
TI  - Antibacterial activity of graphene supported FeAg bimetallic nanocomposites.
AB  - We report the simple one pot synthesis of iron-silver (FeAg) bimetallic
      nanoparticles with different compositions on graphene support. The nanoparticles
      are well dispersed on the graphene sheet as revealed by the TEM, XRD, and Raman
      spectra. The antibacterial activity of graphene-FeAg nanocomposite (NC) towards
      Bacillus subtilis, Escherichia coli, and Staphylococcus aureus was investigated
      by colony counting method. Graphene-FeAg NC demonstrates excellent antibacterial
      activity as compared to FeAg bimetallic without graphene. To understand the
      antibacterial mechanism of the NC, oxidative stress caused by reactive oxygen
      species (ROS) and the glutathione (GSH) oxidation were investigated in the
      system. It has been observed that ROS production and GSH oxidation are
      concentration dependent while the increase in silver content up to 50% generally
      enhances the ROS production while ROS decreases on further increase in silver
      content. Graphene loaded FeAg NC demonstrates higher GSH oxidation capacity than
      bare FeAg bimetallic nanocomposite. The mechanism study suggests that the
      antibacterial activity is probably due to membrane and oxidative stress produced
      by the nanocomposites. The possible antibacterial pathway mainly includes the non
      ROS oxidative stress (GSH oxidation) while ROS play minor role. 

PMID- 27038915
TI  - Polyphenol stabilized colloidal gold nanoparticles from Abutilon indicum leaf
      extract induce apoptosis in HT-29 colon cancer cells.
AB  - Green synthesized gold nanoparticles have received substantial attention owing to
      their biomedical applications, particularly in cancer therapy. Although
      anticancer activities of green synthesized gold nanoparticles have been reported
      earlier, the underlying mechanism behind their anticancer activity is still to be
      understood. The present study, describes the green synthesis of Abutilon indicum
      gold nanoparticles (AIGNPs) from Abutilon indicum leaf extract (AILE) and their
      cytotoxic mechanism in colon cancer cells. Dimensions of spherical shaped AIGNPs
      were found to be in the range of 1-20nm as determined by TEM. GC-MS and FTIR
      analysis indicated the presence of polyphenolic groups in AILE, which might have
      been involved in the stabilization of AIGNPs. In vitro free radical scavenging
      analysis revealed the radical quenching activity of AIGNPs. Further, the AIGNPs
      exhibited cytotoxicity in HT-29 colon cancer cells with IC50 values of 210 and
      180MUg/mL after 24 and 48h. This was mediated through nuclear morphological
      changes and cell membrane damage as evidenced by acridine orange/ethidium
      bromide, propidium iodide and AnnexinV-Cy3 staining methods. Mechanism of the
      observed cytotoxicity of AIGNPs was explained on the basis of increased levels of
      reactive oxygen species and simultaneous reduction in cellular antioxidants,
      which might have caused mitochondrial membrane potential loss, DNA damage and
      G1/S phase cell cycle arrest. Expression of cleaved Caspase-9, Caspase-8, Caspase
      3, Lamin A/C and PARP, provided the clues for the induction of intrinsic and
      extrinsic apoptosis pathways in AIGNPs treated HT-29 cells. The study provides a
      preliminary guidance towards the development of colon cancer therapy using green
      synthesized gold nanoparticles. 

PMID- 27038916
TI  - Antioxidative and antiinflammatory activities of quercetin-loaded silica
      nanoparticles.
AB  - Utilizing the biological activities of compounds by encapsulating natural
      components in stable nanoparticles is an important strategy for a variety of
      biomedical and healthcare applications. In this study, quercetin-loaded silica
      nanoparticles were synthesized using an oil-in-water microemulsion method, which
      is a suitable system for producing functional nanoparticles of controlled size
      and shape. The resulting quercetin-loaded silica nanoparticles were spherical,
      highly monodispersed, and stable in an aqueous system. Superoxide radical
      scavenging effects were found for the quercetin-loaded silica nanoparticles as
      well as free quercetin. The quercetin-loaded silica nanoparticles showed cell
      viability comparable to that of the controls. The amounts of proinflammatory
      cytokines produced by macrophages, such as interleukin 1 beta, interleukin 6, and
      tumor necrosis factor alpha, were reduced significantly for the quercetin-loaded
      silica nanoparticles. These results suggest that the antioxidative and
      antiinflammatory activities of quercetin are maintained after encapsulation in
      silica. Silica nanoparticles can be used for the effective and stable
      incorporation of biologically active natural components into composite
      biomaterials. 

PMID- 27038917
TI  - Physicochemical analysis of initial adhesion and biofilm formation of
      Methanosarcina barkeri on polymer support material.
AB  - The retention of selective biofilms of Methanosarcina species within anaerobic
      digesters could reduce start-up times and enhance the efficiency of the process
      in treating high-strength domestic sewage. The objective of the study was to
      examine the effect of the surface characteristics of six common polymer support
      materials on the initial adhesion of the model methanogen, Methanosarcina
      barkeri, and to assess the potential of these support materials as selective
      biofilm carriers. Results from both the initial adhesion tests and extended DLVO
      (xDLVO) model correlated with each other, with PVC (12% surface coverage/mm(2)),
      PTFE (6% surface coverage/mm(2)), and PP (6% surface coverage/mm(2)), shown to be
      the better performing support materials for initial adhesion, as well as
      subsequent biofilm formation by M. barkeri after 72h. Experimental results of
      these three support materials showed that the type of material strongly
      influenced the extent of adhesion from M. barkeri (p<0.0001), and the xDLVO model
      was able to explain the results in these environmental conditions. Therefore,
      DLVO physicochemical forces were found to be influential on the initial adhesion
      of M. barkeri. Scanning electron microscopy suggested that production of
      extracellular polymeric substances (EPS) from M. barkeri could facilitate further
      biofilm development. This study highlights the potential of using the xDLVO model
      to rapidly identify suitable materials for the selective adhesion of M. barkeri,
      which could be beneficial in both the start-up and long-term phases of anaerobic
      digestion. 

PMID- 27038918
TI  - Transmural Placement of Endocardial Pacing Leads in Patients With Congenital
      Heart Disease.
AB  - BACKGROUND: This study evaluates the feasibility and outcomes of transmural
      placement of endocardial leads (TML) in patients with congenital heart disease.
      METHODS: Between October 2009 and May 2015, 29 TML procedures were performed in
      27 patients. Leads are grouped according to their pacing site: atrial (TML-A, n =
      24) or ventricular (TML-V, n = 12). The TML-V includes transatrial and
      transventricular approaches. Clinical outcome, functional properties of TML, and
      Kaplan-Meier freedom from lead dysfunction were evaluated. RESULTS: Median age
      was 4 years (range, 29 days to 43 years). Median follow-up duration was 2 years
      (range, 1 day to 5.7 years). There was no early mortality. Three late deaths were
      observed (2 unrelated, 1 related to pacing). In group TML-A, no lead dysfunction
      was noted. In group TML-V, there were 3 lead dislodgements and 1 lead fracture.
      Kaplan-Meier freedom from lead dysfunction after 0.5, 1, and 5 years,
      respectively, was 100% in group TML-A and 82% +/- 11%, 73% +/- 13%, and 59% +/-
      17% in group TML-V (log rank p < 0.01). Mean acute (at implantation) and chronic
      (at last follow-up) sensing thresholds were 3.1 +/- 2.3 mV and 3.5 +/- 2.5 mV in
      group TML-A and 11.6 +/- 4.9 mV and 7.5 +/- 4.6 mV in group TML-V, respectively.
      Mean acute and chronic pacing thresholds at 0.5 ms were 1.1 +/- 0.6 V and 0.6 +/-
      0.3 V in group TML-A and 1.0 +/- 0.6 V and 0.9 +/- 0.5 V in group TML-V,
      respectively. CONCLUSIONS: The transmural approach provides an alternative method
      in patients with congenital cardiac defects who cannot receive transvenous leads
      and who have extensive epicardial scarring. Subanalysis shows superior midterm
      performance for TML-A compared with TML-V.

PMID- 27038919
TI  - Modelling the risk of transfusion transmission from travelling donors.
AB  - BACKGROUND: The EUFRAT (European Up-Front Risk Assessment Tool) was developed as
      an online risk assessment tool ( http://eufrattool.ecdc.europa.eu ) to help
      decision-makers assess the transmission risk of emerging infectious diseases
      (EID) through blood transfusion. The aim of this study is to extend the
      methodology developed in the EUFRAT project to quantify the transfusion
      transmission (TT) risk from travelling donors. METHODS: A generic model for
      estimating the TT risk from a group of travelling donors that visited an EID risk
      area was developed. In addition, the new model distinguishes projected future
      transmissions from those that have already occurred. As an illustration the model
      was applied to the outbreaks of chikungunya in Italy in 2007 and Q fever in the
      Netherlands in 2007-2009. RESULTS: Formulas for calculating the travelling
      donors' TT risk were derived. For the chikungunya outbreak in Italy an early
      intervention (at the end of week 7 after the start of the outbreak, so after only
      19% of all cases) would have been required to prevent only 41% of all expected
      transmissions at that time. For Q fever, in which the transmission of chronic Q
      fever is considered, even at the end of the third annual outbreak's peak 47% of
      all (chronic) Q fever transmissions could still be prevented. CONCLUSIONS: The
      updated model allows estimation of the infection transmission risk from
      travelling donors. In combination with the distinction between past and future
      transmissions, these estimates provide valuable information to support decisions
      concerning communication with the public and/or the implementation of safety
      interventions.

PMID- 27038921
TI  - Porta hepatic schwannoma: case report and a 30-year review of the literature
      yielding 15 cases.
AB  - BACKGROUND: Schwannomas located in the periportal region are extremely rare. Only
      14 cases have been reported in the medical literature worldwide. Cases of porta
      hepatic schwannomas reported in the literature worldwide were reviewed. As a
      result, it is very challenging for surgeons to make a preoperative diagnosis due
      to its rarity and nonspecific imaging manifestations. CASE PRESENTATION: A 57
      year-old Chinese female was admitted to our institution with complaint of upper
      abdominal distension and the abdominal CT in the local hospital revealed a
      hypodense mass in the porta hepatis. A fine needle aspiration (FNA) was made to
      confirm the diagnosis, but the result was just suggestive of spindle cell
      neoplasia. Eventually, the patient underwent surgery and postoperative pathology
      confirmed schwannoma in porta hepatis. The patient recovered uneventfully with no
      evidence of recurrence after a follow-up period of 41 months. CONCLUSIONS: It is
      essential for the final diagnosis of porta hepatic schwannomas to combine
      histological examination with immunohistochemistry after surgery. The main
      treatment of porta hepatic schwannomas is complete excision with free margins and
      no lymph node dissection. In some cases, biliary reconstruction or the proper
      hepatic and the gastroduodenal artery resection was performed because the tumor
      was inseparably attached to the extrahepatic bile duct or the proper hepatic and
      the gastroduodenal artery. Malignant transformation of schwannomas is very rare
      and the overall prognosis is satisfactory.

PMID- 27038920
TI  - Corticosteroid therapy in refractory shock following cardiac arrest: a
      randomized, double-blind, placebo-controlled, trial.
AB  - BACKGROUND: The purpose of this study was to determine whether the provision of
      corticosteroids improves time to shock reversal and outcomes in patients with
      post-cardiac arrest shock. METHODS: We conducted a randomized, double-blind trial
      of post-cardiac arrest patients in shock, defined as vasopressor support for a
      minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg
      or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint
      was time to shock reversal. RESULTS: Fifty patients were included with 25 in each
      group. There was no difference in time to shock reversal between groups (hazard
      ratio: 0.83 [95% CI: 0.40-1.75], p = 0.63). We found no difference in secondary
      outcomes including shock reversal (52% vs. 60%, p = 0.57), good neurological
      outcome (24% vs. 32%, p = 0.53) or survival to discharge (28% vs. 36%, p = 0.54)
      between the hydrocortisone and placebo groups. Of the patients with a baseline
      cortisol < 15 ug/dL, 100% (6/6) in the hydrocortisone group achieved shock
      reversal compared to 33% (1/3) in the placebo group (p = 0.08). All patients in
      the placebo group died (100%; 3/3) whereas 50% (3/6) died in the hydrocortisone
      group (p = 0.43). CONCLUSIONS: In a population of cardiac arrest patients with
      vasopressor-dependent shock, treatment with hydrocortisone did not improve time
      to shock reversal, rate of shock reversal, or clinical outcomes when compared to
      placebo. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00676585,
      registration date: May 9, 2008.

PMID- 27038922
TI  - Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF
      kB signaling pathway.
AB  - AIM: The aim of the present study is to explore whether atorvastatin improves
      intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway
      in TNBS-induced rat colitis. METHODS: Acute colitis was induced by intra-rectal
      administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty
      four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and
      sulfasalazine (100 mg/kg) were given to the animals by oral route. This was
      repeated daily for 1 week. Body weight changes, macroscopic and microscopic
      lesions were assessed. MPO and TNF-alpha activities were detected by
      immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-kappaB
      p65 proteins were measured by western blotting analysis. RESULTS: Atorvastatin
      and sulfasalazine reduced the body weight loss, macroscopic and microscopic
      lesions. Additionally, both drugs decreased the expression of MPO and TNF-alpha
      positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced
      expression of TLR4, MyD88 and NF-kappaB p65 proteins. CONCLUSIONS: It is
      suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat
      colitis may involve the inhibition of the TLR4/NFkB signaling pathway.

PMID- 27038923
TI  - Immunoblot screening of CRISPR/Cas9-mediated gene knockouts without selection.
AB  - BACKGROUND: Targeted genomic editing using the CRISPR/Cas9 methodology has opened
      exciting new avenues in probing gene function in virtually any model system,
      including cultured mammalian cells. Depending on the desired mutation, several
      experimental options exist in the isolation of clonal lines, such as selection
      with introduced markers, or screening by PCR amplification of genomic DNA.
      However, streamlined approaches to establishing deletion and tagging mutants with
      minimal genomic perturbation are of interest in applying this methodology.
      RESULTS: We developed a procedure for rapid screening of clonal cell lines for
      the deletion of a protein of interest following CRISPR/Cas9 targeting in the
      absence of selective pressure based on dot immunoblots. To assess the technique,
      we probed clonal isolates of 293-TREx cells that were targeted with three
      separate sgRNAs against the HuR gene. Validation of knockout candidates by
      western blot indicated that the normalized protein abundances indicated by the
      dot blot serve as accurate predictors of deletion. In total, 32 independent
      biallelic deletion lines out of 248 screened clones were isolated, and recovery
      of null mutants ranged from 6 to 36% for the individual sgRNAs. Genomic
      sequencing verified small deletions at the targeted locus. CONCLUSIONS: Clonal
      screening for CRISPR/Cas9-mediated editing events using dot immunoblot is a
      straightforward and efficient approach that facilitates rapid generation of
      genomic mutants to study gene function.

PMID- 27038924
TI  - Efficacy and safety of intravenous paracetamol in comparison to ibuprofen for the
      treatment of patent ductus arteriosus in preterm infants: study protocol for a
      randomized control trial.
AB  - BACKGROUND: Patent ductus arteriosus (PDA) is one of most common complications in
      preterm infants. Although ibuprofen represents the first choice for the closure
      of PDA, this treatment can cause severe gastrointestinal and adverse renal
      effects and worsen platelet function. The successful closure of the PDA with
      paracetamol has been recently reported in several preterm infants, and the safety
      of paracetamol for this use has been suggested by the available data.
      METHODS/DESIGN: We present the design of a randomized, multicenter, controlled
      study, whose aim is to assess the effectiveness and safety of intravenous
      paracetamol in comparison to intravenous ibuprofen for the treatment of PDA in
      preterm infants. A total of 110 infants born at 25(+0) to 31(+6) weeks of
      gestational age will be enrolled and randomized to receive paracetamol or
      ibuprofen (55 patients per group) starting at 24-72 h of life. The primary
      endpoint of the study is the comparison of the PDA closing rate observed after a
      3-day course with paracetamol or ibuprofen. The secondary endpoints include the
      closure rate of PDA after the second course of treatment with ibuprofen, the re
      opening rate of the PDA, the incidence of surgical ligation, and the occurrence
      of adverse effects. DISCUSSION: The results of this study will provide new
      information about the possible use of paracetamol in the treatment of PDA.
      Paracetamol could offer several important therapeutic advantages over current
      treatment options, and it could become the treatment of choice for the management
      of PDA, mainly due to its more favorable side effect profile. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02422966 . Eudract no. 2013-003883-30.

PMID- 27038925
TI  - Characterization of a Plasmodium berghei sexual stage antigen PbPH as a new
      candidate for malaria transmission-blocking vaccine.
AB  - BACKGROUND: Transmission-blocking vaccines (TBVs) are a promising strategy for
      malaria control and elimination. However, candidate TBV antigens are currently
      limited, highlighting the urgency of identifying new antigens for TBV
      development. METHODS: Using a combination of bioinformatic analysis and
      functional studies in the rodent malaria model Plasmodium berghei, we identified
      a conserved Plasmodium protein PbPH (PBANKA_041720) containing a pleckstrin
      homology (PH) domain. The expression of PbPH was detected by Western blot and
      indirect immunofluorescence assay (IFA). The function of PbPH was tested by
      genetic knockout. The TB activity was confirmed by in vitro ookinete conversion
      assay and mosquito feeding. RESULTS: PbPH was detected in Western blot as highly
      expressed in sexual stages (gametocytes and ookinetes). IFA revealed
      localizations of PbPH on the surface of gametes, zygotes, and ookinetes. Deletion
      of the pbph gene did not affect asexual growth, but significantly reduced the
      formation of gametocytes, ookinetes, and oocysts, indicating that PbPH protein is
      required for parasite sexual development. Recombinant PbPH expressed and purified
      from bacteria elicited strong antibody responses in mice and the antibodies
      significantly inhibited exflagellation of male gametocytes and formation of
      ookinetes in a concentration-dependent manner. Mosquito feeding experiments
      confirmed that mosquitoes fed on mice immunized with PbPH had 13 % reduction in
      the prevalence of infection and almost 48 % reduction in oocyst density.
      CONCLUSIONS: Pbph is a highly conserved Plasmodium gene and is required for
      parasite sexual development. PbPH protein is expressed on the surface of gametes
      and ookinetes. Immunization of mice against the recombinant PbPH protein induced
      strong antibody responses that effectively reduced the formation of male gametes
      and ookinetes in vitro and blocked transmission of the parasites to mosquitoes.
      These results highlight PbPH as a potential TBV candidate that is worth future
      investigations in human malaria parasites.

PMID- 27038926
TI  - Natural Xanthones from Garcinia mangostana with Multifunctional Activities for
      the Therapy of Alzheimer's Disease.
AB  - Natural xanthones have diversity pharmacological activities. Here, a series of
      xanthones isolated from the pericarps of Garcinia mangostana Linn, named alpha
      Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D,
      and gamma-Mangostin were investigated. Biological screening performed in vitro
      and in Escherichia coli cells indicated that most of the xanthones exhibited
      significant inhibition of self-induced beta-amyloid (Abeta) aggregation and also
      beta-site amyloid precursor protein-cleaving enzyme 1, acted as potential
      antioxidants and biometal chelators. Among these compounds, alpha-Mangostin,
      Gartanin, Garcinone C and gamma-Mangostin showed better antioxidant properties to
      scavenge Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) free radical than
      Trolox, and potent neuroprotective effects against glutamate-induced HT22 cell
      death partly by up-regulating HO-1 protein level and then scavenging reactive
      oxygen species. Moreover, Gartanin, Garcinone C and gamma-Mangostin could be able
      to penetrate the blood-brain barrier (BBB) in vitro. These findings suggest that
      the natural xanthones have multifunctional activities against Alzheimer's disease
      (AD) and could be promising compounds for the therapy of AD. 

PMID- 27038927
TI  - Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative
      Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.
AB  - Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic
      compound, is widely used as a flavoring additive in food, beverage, cosmetic and
      drug industries. It is reported to cross the blood brain barrier and also
      displayed antioxidant and neuroprotective activities. We previously reported the
      neuroprotective effect of vanillin against rotenone induced in in vitro model of
      PD. The present experiment was aimed to analyze the neuroprotective effect of
      vanillin on the motor and non-motor deficits, neurochemical variables, oxidative,
      anti-oxidative indices and the expression of apoptotic markers against rotenone
      induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor
      and non-motor impairments, neurochemical deficits, oxidative stress and
      apoptosis, whereas oral administration of vanillin attenuated the above-said
      indices. However further studies are needed to explore the mitochondrial
      protective and anti-inflammatory properties of vanillin, as these processes play
      a vital role in the cause and progression of PD. 

PMID- 27038928
TI  - Modulation of NMDA Receptor Subunits Expression by Concanavalin A.
AB  - The processes of N-methyl-D-aspartate (NMDA) receptor subunits expression were
      examined in cortical neurons and rat brain in order to investigate how the
      concanavalin A (Con A) modulates neuronal cells. Con A modulated the expression
      of NMDA receptor subunits in cultured cortical cells. Con A augmented the level
      of intracellular Ca(2+) by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate
      (AMPA). We determined whether activation of AMPA receptors was involved in the
      regulation of NMDA receptor expression with Con A by blocking the desensitization
      of AMPA receptors. The results showed that AMPA receptor antagonists suppressed
      NMDA receptor subunits expression in Con A-treated cortical neuronal cells. PMA
      elevated the expression of NMDA receptor subunits, while PKC inhibitor and
      tyrosine kinases inhibitor suppressed the expression of NMDA receptor subunits.
      Furthermore, it was shown that NMDA receptor subunits expression was modulated in
      a region-specific manner after the sustained microinfusion of Con A into the
      cerebroventricle of the rat brain. Collectively, it could be presumed that the
      AMPA receptor activation was involved in Con A-induced modulation of NMDA
      receptor subunits expression. 

PMID- 27038929
TI  - (-)-Epigallocatechin Gallate Inhibits Asymmetric Dimethylarginine-Induced Injury
      in Human Brain Microvascular Endothelial Cells.
AB  - (-)-Epigallocatechin gallate (EGCG) is the main polyphenol component of green tea
      (leaves of the Camellia sinensis plant). EGCG has been reported to protect human
      brain microvascular endothelial cells (HBMECs) against injury in several models.
      However, the exact mechanism is still unclear. In the current study we found that
      EGCG protected against asymmetric dimethylarginine (ADMA)-induced HBMEC injury,
      and inhibited ADMA-induced reactive oxygen species production and malondialdehyde
      expression. At the same time, we found that pretreatment with EGCG attenuated the
      upregulation of Bax and the downregulation of Bcl-2, thus confirming the cellular
      protective properties of EGCG against ADMA-induced apoptosis. Furthermore, we
      found that EGCG inhibited ADMA-induced phosphorylation of ERK1/2 and p-38, whose
      inhibitors relieved HBMEC injury. In conclusion, EGCG can protect against ADMA
      induced HBMEC injury via the ERK1/2 and p38 MAPK pathways, which are involved in
      the underlying mechanisms of HBMEC injury in cerebral infarction. 

PMID- 27038930
TI  - Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated
      with Glioma Development and Tumor-Associated Epilepsy.
AB  - Level of adenosine, an endogenous astrocyte-based neuromodulator, is primarily
      regulated by adenosine P1 receptors. This study assessed expression of adenosine
      P1 receptors, ADORA1 (adenosine A1 receptor) and ADORA2A (adenosine A2a receptor)
      and their association with glioma development and epilepsy in glioma patients.
      Expression of ADORA1/ADORA2A was assessed immunohistochemically in 65 surgically
      removed glioma tissue and 21 peri-tumor tissues and 8 cases of normal brain
      tissues obtained from hematoma patients with cerebral trauma. Immunofluorescence,
      Western blot, and qRT-PCR were also used to verify immunohistochemical data.
      Adenosine P1 receptor ADORA1 and ADORA2A proteins were localized in the cell
      membrane and cytoplasm and ADORA1/ADORA2A immunoreactivity was significantly
      stronger in glioma and peri-tumor tissues that contained infiltrating tumor cells
      than in normal brain tissues (p < 0.05). The World Health Organization (WHO)
      grade III gliomas expressed even higher level of ADORA1 and ADORA2A. Western blot
      and qRT-PCR confirmed immunohistochemical data. Moreover, higher levels of ADORA1
      and ADORA2A expression occurred in high-grade gliomas, in which incidence of
      epilepsy were lower (p < 0.05). In contrast, a lower level of ADORA1/ADORA2A
      expression was found in peri-tumor tissues with tumor cell presence from patients
      with epilepsy compared to patients without epilepsy (p < 0.05). The data from the
      current study indicates that dysregulation in ADORA1/ADORA2A expression was
      associated with glioma development, whereas low level of ADORA1/ADORA2A
      expression could increase susceptibility of tumor-associated epilepsy. 

PMID- 27038931
TI  - Stromal Cell-Derived Factor 1 Increases Tetrodotoxin-Resistant Sodium Currents
      Nav1.8 and Nav1.9 in Rat Dorsal Root Ganglion Neurons via Different Mechanisms.
AB  - Stromal cell-derived factor 1 (SDF-1)/chemokine CXC motif ligand 12 (CXCL12), a
      chemokine that is upregulated in dorsal root ganglion (DRG) during chronic pain
      models, has recently been found to play a central role in pain hypersensitivity.
      The purpose of present study is to investigate the functional impact of SDF-1 and
      its receptor, chemokine CXC motif receptor 4 (CXCR4), on two TTXR sodium channels
      in rat DRG using electrophysiological techniques. Preincubation with SDF-1 caused
      a concentration-dependent increase of Nav1.8 and Nav1.9 currents amplitudes in
      acutely isolated small diameter DRG neurons in short-term culture. As to Nav1.9,
      changes in current density and kinetic properties of Nav1.9 current evoked by SDF
      1(50 ng/ml) was eliminated by CXCR4 antagonist AMD3100 and phosphatidylinositol 3
      kinase (PI3K) inhibitor LY294002. The increase in Nav1.9 current was also blocked
      by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of Gi/o
      but not Gs subunits. As to Nav1.8, inhibitors (AMD3100, PTX, CTX, LY294002) used
      in present study didn't inhibit the increased amplitude of Nav1.8 current and
      shifted activation curve of Nav1.8 in a hyperpolarizing direction in the presence
      of SDF-1 (50 ng/ml). In conclusion, our data demonstrated that SDF-1 may excite
      primary nociceptive sensory neurons by acting on the biophysical properties of
      Nav1.8 and Nav1.9 currents but via different mechanisms. 

PMID- 27038932
TI  - Expression and Prognostic Significance of p53 in Glioma Patients: A Meta
      analysis.
AB  - Glioma is a brain tumor deriving from the neoplastic glial cells or neuroglia.
      Due to its resistance to anticancer drugs and different disease progress of
      individuals, patients with high-grade glioma are difficult to completely cure,
      leading to a poor prognosis and low overall survival. Therefore, there is an
      urgent need to look for prognostic and diagnostic indicators that can predict
      glioma grades. P53 is one of the widely studied biomarkers in human glioma. The
      purpose of this study was to comprehensively evaluate the significance of p53
      expression in glioma grades and overall survival. We searched commonly used
      electronic databases to retrieve related articles of p53 expression in glioma.
      Overall, a total of 21 studies including 1322 glioma patients were finally
      screened out. We observed that the frequency of p53 immuno-positivity was higher
      in high-grade patients than that in low-grade category (63.8 vs. 41.6 %), and our
      statistic analysis indicated that p53 expression was associated with pathological
      grade of glioma (OR 2.93, 95 % CI 1.87-4.60, P < 0.00001). This significant
      correction was also found in 1-, 3- and 5-year overall survival. However, no
      positive relationship was found between age, sex, tumor size and p53 expression
      in patients with glioma. In conclusion, our results suggested that p53
      immunohistochemical expression might have an effective usefulness in predicting
      the prognosis in patients with glioma. 

PMID- 27038933
TI  - Impaired Purinergic Regulation of the Glial (Muller) Cell Volume in the Retina of
      Transgenic Rats Expressing Defective Polycystin-2.
AB  - Retinal glial (Muller) cells possess an endogenous purinergic signal transduction
      cascade which normally prevents cellular swelling in osmotic stress. The cascade
      can be activated by osmotic or glutamate receptor-dependent ATP release. We
      determined whether activation of this cascade is altered in Muller cells of
      transgenic rats that suffer from a slow photoreceptor degeneration due to the
      expression of a truncated human cilia gene polycystin-2 (CMV-PKD21/703 HA). Age
      matched Sprague-Dawley rats served as control. Retinal slices were superfused
      with a hypoosmotic solution (60 % osmolarity). Muller cells in retinas of
      PKD21/703 rats swelled immediately in hypoosmotic stress; this was not observed
      in control retinas. Pharmacological blockade of P2Y1 or adenosine A1 receptors
      induced osmotic swelling of Muller cells from control rats. The swelling induced
      by the P2Y1 receptor antagonist was mediated by induction of oxidative
      nitrosative stress, mitochondrial dysfunction, production of inflammatory lipid
      mediators, and a sodium influx from the extracellular space. Exogenous VEGF or
      glutamate prevented the hypoosmotic swelling of Muller cells from PKD21/703 rats;
      this effect was mediated by activation of the purinergic signaling cascade. In
      neuroretinas of PKD21/703 rats, the gene expression levels of P2Y1 and A1
      receptors, pannexin-1, connexin 45, NTPDases 1 and 2, and various subtypes of
      nucleoside transporters are elevated compared to control. The data may suggest
      that the osmotic swelling of Muller cells from PKD21/703 rats is caused by an
      abrogation of the osmotic ATP release while the glutamate-induced ATP release is
      functional. In the normal retina, ATP release and autocrine P2Y1 receptor
      activation serve to inhibit the induction of oxidative-nitrosative stress,
      mitochondrial dysfunction, and production of inflammatory lipid mediators, which
      otherwise will induce a sodium influx and cytotoxic Muller cell swelling under
      anisoosmotic conditions. Purinergic receptors may represent a target for the
      protection of retinal glial cells from mitochondrial oxidative stress. 

PMID- 27038934
TI  - Coronary MR angiography at 3T: fat suppression versus water-fat separation.
AB  - OBJECTIVES: To compare Dixon water-fat suppression with spectral pre-saturation
      with inversion recovery (SPIR) at 3T for coronary magnetic resonance angiography
      (MRA) and to demonstrate the feasibility of fat suppressed coronary MRA at 3T
      without administration of a contrast agent. MATERIALS AND METHODS: Coronary MRA
      with Dixon water-fat separation or with SPIR fat suppression was compared on a 3T
      scanner equipped with a 32-channel cardiac receiver coil. Eight healthy
      volunteers were examined. Contrast-to-noise ratio (CNR), signal-to-noise ratio
      (SNR), right coronary artery (RCA), and left anterior descending (LAD) coronary
      artery sharpness and length were measured and statistically compared. Two
      experienced cardiologists graded the visual image quality of reformatted Dixon
      and SPIR images (1: poor quality to 5: excellent quality). RESULTS: Coronary MRA
      images in healthy volunteers showed improved contrast with the Dixon technique
      compared to SPIR (CNR blood-fat: Dixon = 14.9 +/- 2.9 and SPIR = 13.9 +/- 2.1; p
      = 0.08, CNR blood-myocardium: Dixon = 10.2 +/- 2.7 and SPIR = 9.11 +/- 2.6; p =
      0.1). The Dixon method led to similar fat suppression (fat SNR with Dixon: 2.1 +/
      0.5 vs. SPIR: 2.4 +/- 1.2, p = 0.3), but resulted in significantly increased SNR
      of blood (blood SNR with Dixon: 19.9 +/- 4.5 vs. SPIR: 15.5 +/- 3.1, p < 0.05).
      This means the residual fat signal is slightly lower with the Dixon compared to
      the SIPR technique (although not significant), while the SNR of blood is
      significantly higher with the Dixon technique. Vessel sharpness of the RCA was
      similar for Dixon and SPIR (57 +/- 7 % vs. 56 +/- 9 %, p = 0.2), while the RCA
      visualized vessel length was increased compared to SPIR fat suppression (107 +/-
      21 vs. 101 +/- 21 mm, p < 0.001). For the LAD, vessel sharpness (50 +/- 13 % vs.
      50 +/- 7 %, p = 0.4) and vessel length (92 +/- 46 vs. 90 +/- 47 mm, p = 0.4) were
      similar with both techniques. Consequently, the Dixon technique resulted in an
      improved visual score of the coronary arteries in the water fat separated images
      of healthy subjects (RCA: 4.6 +/- 0.5 vs. 4.1 +/- 0.7, p = 0.01, LAD: 4.1 +/- 0.7
      vs. 3.5 +/- 0.8, p = 0.007). CONCLUSIONS: Dixon water-fat separation can
      significantly improve coronary artery image quality without the use of a contrast
      agent at 3T.

PMID- 27038935
TI  - Scan time minimization in hepatic diffusion-weighted imaging: evaluation of the
      simultaneous multislice acceleration technique with different acceleration
      factors and gradient preparation schemes.
AB  - OBJECTIVE: To evaluate simultaneous multislice (sms) accelerated diffusion
      weighted imaging (DWI) of the liver in comparison to conventional sequences.
      MATERIALS AND METHODS: Ten volunteers underwent DWI of the liver at 1.5 T. Four
      different sms-accelerated sequences with monopolar and bipolar gradient
      preparation (MP, BP) and acceleration factors 2 and 3 (sms2-DWI, sms3-DWI) were
      compared to conventional DWI (c-DWI). Image quality criteria rated on a 5-point
      Likert scale (5 = excellent), image quality sum scores (maximum 120), and ADC
      were compared using Friedman test and Dunn-Bonferroni post hoc test. Bland-Altman
      plots were calculated for ADC comparison. p values <0.05 were considered
      significant. RESULTS: Sms2-DWI offered scan time minimization of 67 % without
      significant difference in image quality (sum score: sms2-DWI MP/BP: 97 +/- 8/92
      +/- 9; c-DWI MP/BP: 99 +/- 8/97 +/- 8). Sms3-DWI offered slight additional scan
      time minimization with significantly inferior image quality (sum score: sms3-DWI
      MP/BP: 75 +/- 14/69 +/- 14; p < 0.001). MP preparation provided slightly higher
      image quality in sms-DWI without statistical significance. ADC in sms-DWI were
      significantly lower (sms2-DWI MP 1.01 * 10(-3) mm(2)/s; c-DWI MP 1.20 * 10(-3)
      mm(2)/s; p < 0.001). CONCLUSION: Sms2-DWI provides considerable scan time
      minimization without significant shortcomings in image quality. Sms3-DWI provides
      significantly inferior image quality without further scan time minimization.
      Potentially lower ADC in sms-DWI should be considered in clinical routine.

PMID- 27038936
TI  - Measurements of RF power reflected and radiated by multichannel transmit MR coils
      at 7T.
AB  - OBJECTIVE: The power balance of multichannel transmit coils is a central
      consideration in assessing performance and safety issues. At ultrahigh fields, in
      addition to absorption and reflection, radiofrequency (RF) radiation into the far
      field becomes a concern. MATERIALS AND METHODS: We engineered a system for in
      situ measurement of complex-valued scattering parameter (S-parameter) matrices of
      multichannel transmit coils that allows for the calculation of the reflected and
      accepted power for arbitrary steering conditions. The radiated power from an RF
      coil inside a large single-mode waveguide couples to that mode. Finite-difference
      time-domain simulations were used for the calculations, and E-field probes were
      used to measure the electric field distribution, and hence the radiated power, in
      the waveguide. To test this concept, an eight-channel shielded-loop array for 7T
      imaging was studied inside a 280-cm-long cylindrical waveguide with a 60-cm
      diameter. RESULTS: For a 7T parallel-transmit coil, the S-parameters were
      measured and the reflected power calculated as a function of steering conditions.
      Maximum radiated power was observed for the circularly polarized mode.
      CONCLUSION: A system was developed for in situ S-parameter measurements combined
      with a method for determining radiated power, allowing a complete assessment of
      the power balance of multichannel transmit coils at 7T.

PMID- 27038937
TI  - Case-oriented pathways analysis in pancreatic adenocarcinoma using data from a
      sleeping beauty transposon mutagenesis screen.
AB  - BACKGROUND: Mutation studies of pancreatic ductal adenocarcinoma (PDA) have
      revealed complicated heterogeneous genomic landscapes of the disease. These
      studies cataloged a number of genes mutated at high frequencies, but also report
      a very large number of genes mutated in lower percentages of tumors. Taking
      advantage of a well-established forward genetic screening technique, with the
      Sleeping Beauty (SB) transposon, several studies produced PDA and discovered a
      number of common insertion sites (CIS) and associated genes that are recurrently
      mutated at high frequencies. As with human mutation studies, a very large number
      of genes were found to be altered by transposon insertion at low frequencies.
      These low frequency CIS associated genes may be very valuable to consider for
      their roles in cancer, since collectively they might emerge from a core group of
      genetic pathways. RESULT: In this paper, we determined whether the genetic
      mutations in SB-accelerated PDA occur within a collated group of biological
      processes defined as gene sets. The approach considered both genes mutated in
      high and lower frequencies. We implemented a case-oriented, gene set enrichment
      analysis (CO-GSEA) on SB altered genes in PDA. Compared to traditional GSEA, CO
      GSEA enables us to consider individual characteristics of mutation profiles of
      each PDA tumor. We identified genetic pathways with higher numbers of genetic
      mutations than expected by chance. We also present the correlations between these
      significant enriched genetic pathways, and their associations with CIS genes.
      CONCLUSION: These data suggest that certain pathway alterations cooperate in PDA
      development.

PMID- 27038938
TI  - Arabidopsis atypical kinase ABC1K1 is involved in red light-mediated development.
AB  - KEY MESSAGE: ABC1K1 functions as a novel negative regulator downstream of phyB
      and HY5 in red light-mediated Arabidopsis development. Light is a key
      environmental factor for plant morphogenesis. To understand the role of ACTIVITY
      OF BC1 COMPLEX KINASE (ABC1K) family members in light-mediated Arabidopsis
      development, we examined the phenotype of abc1k mutants under various light
      conditions. We show that abc1k1 mutants display significantly short hypocotyls
      specifically under continuous red light and this effect is more apparent under
      higher red light fluence rates. The expression of PHYTOCHROME-INTERACTING FACTORs
      (PIFs), transcription factors in red light signaling, is repressed in abc1k1
      mutants under continuous red light. The expression pattern of ABC1K1 is
      independent of light conditions. Furthermore, genetic analysis indicates that
      abc1k1 almost completely suppresses the long hypocotyl phenotype of phyB and hy5.
      However, the mutation of ABC1K3, one homolog of ABC1K1, reverses the inhibition
      of hypocotyl elongation in phyB and hy5 by abc1k1. Together, our research
      describes novel characteristics for ABC1K1 in seedling stage and defines it as a
      novel negative component in red light-mediated Arabidopsis development.

PMID- 27038939
TI  - Consumer acceptance of food crops developed by genome editing.
AB  - One of the major problems regarding consumer acceptance of genetically modified
      organisms (GMOs) is the possibility that their transgenes could have adverse
      effects on the environment and/or human health. Genome editing, represented by
      the CRISPR/Cas9 system, can efficiently achieve transgene-free gene modifications
      and is anticipated to generate a wide spectrum of plants. However, the public
      attitude against GMOs suggests that people will initially be unlikely to accept
      these plants. We herein explored the bottlenecks of consumer acceptance of
      transgene-free food crops developed by genome editing and made some
      recommendations. People should not pursue a zero-risk bias regarding such crops.
      Developers are encouraged to produce cultivars with a trait that would satisfy
      consumer needs. Moreover, they should carefully investigate off-target mutations
      in resultant plants and initially refrain from agricultural use of multiplex
      genome editing for better risk-benefit communication. The government must
      consider their regulatory status and establish appropriate regulations if
      necessary. The government also should foster communication between the public and
      developers. If people are informed of the benefits of genome editing-mediated
      plant breeding and trust in the relevant regulations, and if careful risk-benefit
      communication and sincere considerations for the right to know approach are
      guaranteed, then such transgene-free crops could gradually be integrated into
      society. 

PMID- 27038940
TI  - Inheritance in doubled-diploid clementine and comparative study with SDR
      unreduced gametes of diploid clementine.
AB  - KEY MESSAGE: Tetraploid clementine displays mainly tetrasomic inheritance.
      Genetic structures of 2n SDR and 2 * gametes from DD clementine are complementary
      and will guides triploids citrus breeding strategies. Triploid breeding is
      developed worldwide to create new seedless cultivars. Citrus triploid hybrids can
      be recovered from 2x * 2x sexual hybridizations as a consequence of the formation
      of unreduced gametes (2n), or from 4x * 2x interploid hybridizations in which
      tetraploid parents used are most often doubled-diploid (DD). Here we have
      analyzed the inheritance in doubled-diploid clementine and compared the genetic
      structures of gametes of DD clementine with SDR unreduced gametes of diploid
      clementine. Parental heterozygosity restitution (PHR) with DD parents depends on
      the rate of preferential chromosome pairing and thus the proportion of disomic
      versus tetrasomic segregations. Doubled-diploid clementine largely exhibited
      tetrasomic segregation. However, three linkage groups had intermediate
      segregation and one had a tendency for disomy. Significant doubled reduction
      rates (DR) rates were observed in six of the nine LGs. Differences of PHR between
      2n SDR and 2x DD gametes were highest in the centromeric region and progressively
      decreased toward the distal regions where they were not significant. Over all
      markers, PHR was lower (two-thirds) in SDR 2n gametes than in DD-derived diploid
      gametes. The two strategies appear complementary in terms of genotypic
      variability. Interploid 4x * 2x hybridization is potentially more efficient for
      developing new cultivars that are phenotypically closer to the diploid parent of
      the DD than sexual hybridization through SDR 2n gametes. Conversely, 2x * 2x
      triploidisation has the potential to produce novel products with characteristics
      for market segmentation strategies.

PMID- 27038941
TI  - The forensic implications of predatory publishing.

PMID- 27038942
TI  - Erratum to: Identification of invasion proteins of Cryptosporidium parvum.

PMID- 27038943
TI  - A Candida guilliermondii lysine hyperproducer capable of elevated citric acid
      production.
AB  - A mutant of the yeast Candida guilliermondii ATCC 9058 exhibiting elevated citric
      acid production was isolated based upon its ability to overproduce lysine. This
      method involved the use of a solid medium containing a combination of lysine
      analogues to identify a mutant that produced a several-fold higher lysine level
      compared to its parent strain using glucose or glycerol as a carbon source. The
      mutant strain was also capable of producing more than a fivefold higher citric
      acid level on glycerol as a carbon source compared to its parent strain. It was
      concluded that the screening of yeast lysine hyperproducer strains could provide
      a rapid approach to isolate yeast citric acid hyperproducer strains. 

PMID- 27038944
TI  - Effect of cuticular waxes compounds from table grapes on growth, germination and
      gene expression in Botrytis cinerea.
AB  - Botrytis cinerea attacks a broad range of host causing significant economic
      losses in the worldwide fruit export industry. Hitherto, many studies have
      focused on the penetration mechanisms used by this phytopathogen, but little is
      known about the early stages of infection, especially those such as adhesion and
      germination. The aim of this work was to evaluate the effect of cuticular waxes
      compounds from table grapes on growth, germination and gene expression of B.
      cinerea. To accomplish this, growth was analyzed using as substrate n-alkanes
      extracted from waxes of fresh fruit (table grapes, blueberries and apricots).
      Subsequently, the main compounds of table grape waxes, oleanolic acid (OA) and n
      fatty alcohols, were mixed to generate a matrix on which conidia of B. cinerea
      were added to assess their effect on germination and expression of bctub, bchtr
      and bchex genes. B. cinerea B05.10, isolated from grapes, increased its growth on
      a matrix composed by table grapes n-alkanes in comparison to a matrix made with n
      alkanes from apricot or blueberries. Moreover, at 2.5 h, B05.10 germination
      increased 17 and 33 % in presence of n-alkanes from table grape, in comparison to
      conditions without alkanes or with blueberries alkanes, respectively. Finally,
      expression of bchtr and bchex showed a significant increase during the first hour
      after contact with n-fatty alcohols and OA. In conclusion, B. cinerea displays
      selectivity towards certain compounds found in host waxes, mainly n-fatty
      alcohols, which could be a good candidate to control this phytopathogen in early
      stages of infection.

PMID- 27038945
TI  - Development of a powder formulation based on Bacillus cereus sensu lato strain
      B25 spores for biological control of Fusarium verticillioides in maize plants.
AB  - Maize is an economically important crop in northern Mexico. Different fungi cause
      ear and root rot in maize, including Fusarium verticillioides (Sacc.) Nirenberg.
      Crop management of this pathogen with chemical fungicides has been difficult. By
      contrast, the recent use of novel biocontrol strategies, such as seed
      bacterization with Bacillus cereus sensu lato strain B25, has been effective in
      field trials. These approaches are not without their problems, since insufficient
      formulation technology, between other factors, can limit success of biocontrol
      agents. In response to these drawbacks, we have developed a powder formulation
      based on Bacillus B25 spores and evaluated some of its characteristics, including
      shelf life and efficacy against F. verticillioides, in vitro and in maize plants.
      A talc-based powder formulation containing 1 * 10(9) c.f.u. g(-1) was obtained
      and evaluated for seed adherence ability, seed germination effect, shelf life and
      antagonism against F. verticillioides in in vitro and in planta assays. Seed
      adherence of viable bacterial spores ranged from 1.0 to 1.41 * 10(7) c.f.u. g(
      1). Bacteria did not display negative effects on seed germination. Spore
      viability for the powder formulation slowly decreased over time, and was 53 %
      after 360 days of storage at room temperature. This formulation was capable of
      controlling F. verticillioides in greenhouse assays, as well as eight other maize
      phytopathogenic fungi in vitro. The results suggest that a talc-based powder
      formulation of Bacillus B25 spores may be sufficient to produce inoculum for
      biocontrol of maize ear and root rots caused by F. verticillioides.

PMID- 27038946
TI  - Fate of virginiamycin through the fuel ethanol production process.
AB  - Antibiotics are frequently used to prevent and treat bacterial contamination of
      commercial fuel ethanol fermentations, but there is concern that antibiotic
      residues may persist in the distillers grains coproducts. A study to evaluate the
      fate of virginiamycin during the ethanol production process was conducted in the
      pilot plant facilities at the National Corn to Ethanol Research Center,
      Edwardsville, IL. Three 15,000-liter fermentor runs were performed: one with no
      antibiotic (F1), one dosed with 2 parts per million (ppm) of a commercial
      virginiamycin product (F2), and one dosed at 20 ppm of virginiamycin product
      (F3). Fermentor samples, distillers dried grains with solubles (DDGS), and
      process intermediates (whole stillage, thin stillage, syrup, and wet cake) were
      collected from each run and analyzed for virginiamycin M and virginiamycin S
      using a liquid chromatography-mass spectrometry method. Virginiamycin M was
      detected in all process intermediates of the F3 run. On a dry-weight basis,
      virginiamycin M concentrations decreased approximately 97 %, from 41 MUg/g in the
      fermentor to 1.4 MUg/g in the DDGS. Using a disc plate bioassay, antibiotic
      activity was detected in DDGS from both the F2 and F3 runs, with values of 0.69
      MUg virginiamycin equivalent/g sample and 8.9 MUg/g, respectively. No antibiotic
      activity (<0.6 MUg/g) was detected in any of the F1 samples or in the fermentor
      and process intermediate samples from the F2 run. These results demonstrate that
      low concentrations of biologically active antibiotic may persist in distillers
      grains coproducts produced from fermentations treated with virginiamycin.

PMID- 27038947
TI  - Improving the yield of (+)-terrein from the salt-tolerant Aspergillus terreus
      PT06-2.
AB  - (+)-Terrein has a potential application for drug discovery. To improve the yield
      of (+)-terrein, two-level Plackett-Burman design and response surface methodology
      methods were used to optimize the condition of a salt-tolerant fungus,
      Aspergillus terreus PT06-2. As a result, the yield of (+)-terrein reached 8.20 +/
      0.072 g/L in a 500-mL flask containing 150 mL optimal medium consisted of 13.1 %
      NaCl, 3.6 % starch, 2 % sodium glutamate, 0.05 % KCl, 3 % inoculum size,
      adjusting initial pH value to 5 with 10 % HCl and shaking for 18 days at 28 
      degrees C and 180 rpm. The production of (+)-terrein was 47.0 % higher than the
      highest production reported in shake flasks. The advantages of this optimization
      are uses of single carbon source and nitrogen source and easy separation and
      purification by recrystallization. The result exhibited the potential and
      advantages of A. terreus PT06-2 in industrial production of (+)-terrein by
      fermentation.

PMID- 27038948
TI  - Fungal communities from the calcareous deep-sea sediments in the Southwest India
      Ridge revealed by Illumina sequencing technology.
AB  - The diversity and ecological significance of bacteria and archaea in deep-sea
      environments have been thoroughly investigated, but eukaryotic microorganisms in
      these areas, such as fungi, are poorly understood. To elucidate fungal diversity
      in calcareous deep-sea sediments in the Southwest India Ridge (SWIR), the
      internal transcribed spacer (ITS) regions of rRNA genes from two sediment
      metagenomic DNA samples were amplified and sequenced using the Illumina
      sequencing platform. The results revealed that 58-63 % and 36-42 % of the ITS
      sequences (97 % similarity) belonged to Basidiomycota and Ascomycota,
      respectively. These findings suggest that Basidiomycota and Ascomycota are the
      predominant fungal phyla in the two samples. We also found that Agaricomycetes,
      Leotiomycetes, and Pezizomycetes were the major fungal classes in the two
      samples. At the species level, Thelephoraceae sp. and Phialocephala fortinii were
      major fungal species in the two samples. Despite the low relative abundance,
      unidentified fungal sequences were also observed in the two samples. Furthermore,
      we found that there were slight differences in fungal diversity between the two
      sediment samples, although both were collected from the SWIR. Thus, our results
      demonstrate that calcareous deep-sea sediments in the SWIR harbor diverse fungi,
      which augment the fungal groups in deep-sea sediments. This is the first report
      of fungal communities in calcareous deep-sea sediments in the SWIR revealed by
      Illumina sequencing.

PMID- 27038949
TI  - Decreased microbial diversity and Lactobacillus group in the intestine of
      geriatric giant pandas (Ailuropoda melanoleuca).
AB  - It has been established beyond doubt that giant panda genome lacks lignin
      degrading related enzyme, gastrointestinal microbes may play a vital role in
      digestion of highly fibrous bamboo diet. However, there is not much information
      available about the intestinal bacteria composition in captive giant pandas with
      different ages. In this study, we compared the intestinal bacterial community of
      12 captive giant pandas from three different age groups (subadults, adults, and
      geriatrics) through PCR-denaturing gradient gel electrophoresis (DGGE) and real
      time PCR analysis. Results indicated that microbial diversity in the intestine of
      adults was significantly higher than that of the geriatrics (p < 0.05), but not
      significant compared to the subadults (p > 0.05). The predominant bands in DGGE
      patterns shared by the twelve pandas were related to Firmicutes and
      Proteobacteria. Additionally, in comparison to healthy individuals, antibiotic
      treated animals showed partial microbial dysbiosis. Real-time PCR analyses
      confirmed a significantly higher abundance of the Lactobacillus in the fecal
      microbiota of adults (p < 0.05), while other bacterial groups and species
      detected did not significantly differ among the three age groups (p > 0.05). This
      study revealed that captive giant pandas with different ages showed different
      intestinal bacteria composition.

PMID- 27038950
TI  - A strain of Meyerozyma guilliermondii isolated from sugarcane juice is able to
      grow and ferment pentoses in synthetic and bagasse hydrolysate media.
AB  - The search for new microbial strains that are able to withstand inhibitors
      released from hemicellulosic hydrolysis and are also still able to convert sugars
      in ethanol/xylitol is highly desirable. A yeast strain isolated from sugarcane
      juice and identified as Meyerozyma guilliermondii was evaluated for the ability
      to grow and ferment pentoses in synthetic media and in sugarcane bagasse
      hydrolysate. The yeast grew in xylose, arabinose and glucose at the same rate at
      an initial medium pH of 5.5. At pH 4.5, the yeast grew more slowly in arabinose.
      There was no sugar exhaustion within 60 h. At higher xylose concentrations with a
      higher initial cell concentration, sugar was exhausted within 96 h at pH 4.5. An
      increase of 350 % in biomass was obtained in detoxified hydrolysates, whereas
      supplementation with 3 g/L yeast extract increased biomass production by
      approximately 40 %. Ethanol and xylitol were produced more significantly in
      supplemented hydrolysates regardless of detoxification. Xylose consumption was
      enhanced in supplemented hydrolysates and arabinose was consumed only when xylose
      and glucose were no longer available. Supplementation had a greater impact on
      ethanol yield and productivity than detoxification; however, the product yields
      obtained in the present study are still much lower when compared to other yeast
      species in bagasse hydrolysate. By the other hand, the fermentation of both
      xylose and arabinose and capability of withstanding inhibitors are important
      characteristics of the strain assayed.

PMID- 27038951
TI  - Evidence of alpha-, beta- and gamma-HCH mixture aerobic degradation by the native
      actinobacteria Streptomyces sp. M7.
AB  - The organochlorine insecticide gamma-hexachlorocyclohexane (gamma-HCH, lindane)
      and its non-insecticidal alpha- and beta-isomers continue to pose serious
      environmental and health concerns, although their use has been restricted or
      completely banned for decades. In this study we report the first evidence of the
      growth ability of a Streptomyces strain in a mineral salt medium containing high
      doses of alpha- and beta-HCH (16.6 mg l(-1)) as a carbon source. Degradation of
      HCH isomers by Streptomyces sp. M7 was investigated after 1, 4, and 7 days of
      incubation, determining chloride ion release, and residues in the supernatants by
      GC with uECD detection. The results show that both the alpha- and beta-HCH
      isomers were effectively metabolized by Streptomyces sp. M7, with 80 and 78 %
      degradation respectively, after 7 days of incubation. Moreover,
      pentachlorocyclohexenes and tetrachlorocyclohexenes were detected as metabolites.
      In addition, the formation of possible persistent compounds such as
      chlorobenzenes and chlorophenols were studied by GC-MS, while no phenolic
      compounds were detected. In conclusion, we have demonstrated for the first time
      that Streptomyces sp. M7 can degrade alpha- and beta-isomers individually or
      combined with gamma-HCH and could be considered as a potential agent for
      bioremediation of environments contaminated by organochlorine isomers.

PMID- 27038952
TI  - Evidence for the involvement of nematocidal toxins of Purpureocillium lilacinum
      6029 cultured on Karanja deoiled cake liquid medium.
AB  - In present study, in vitro nematocidal bioassays, FT-IR and HPLC analysis were
      employed to demonstrate the involvement of toxins of Purpureocillium lilacinum in
      killing root-knot nematodes (Meloidogyne incognita). During growth study, maximum
      mycelial biomass (10.52 g/l) in de-oiled Karanja cake medium was achieved on 8th
      day while complete mortality of nematodes was obtained by 6th day filtrate
      (FKSM). Maximum production of crude nematocidal toxin was recorded on 7th day
      suggesting that the toxin production was paralleled with growth of the fungus.
      The median lethal concentration (LC50) determined for the crude toxin from 6th
      day to 10th day ranged from 89.41 to 43.21 ppm. The median lethal time (LT50) for
      the crude toxin of FKSM was found to be 1.46 h. This is the first report of
      implementing a comparative infra-red spectroscopy coupled with HPLC analysis to
      predict the presence of nematocidal toxin in the fungal filtrate cultured on
      Karanja deoiled cake liquid medium.

PMID- 27038953
TI  - Enhanced green fluorescent protein (egfp) gene expression in Tetraselmis
      subcordiformis chloroplast with endogenous regulators.
AB  - On the basis of fundamental genetic transformation technologies, the goal of this
      study was to optimize Tetraselmis subcordiformis chloroplast transformation
      through the use of endogenous regulators. The genes rrn16S, rbcL, psbA, and psbC
      are commonly highly expressed in chloroplasts, and the regulators of these genes
      are often used in chloroplast transformation. For lack of a known chloroplast
      genome sequence, the genome-walking method was used here to obtain full sequences
      of T. subcordiformis endogenous regulators. The resulting regulators, including
      three promoters, two terminators, and a ribosome combination sequence, were
      inserted into the previously constructed plasmid pPSC-R, with the egfp gene
      included as a reporter gene, and five chloroplast expression vectors prepared.
      These vectors were successfully transformed into T. subcordiformis by particle
      bombardment and the efficiency of each vector tested by assessing EGFP
      fluorescence via microscopy. The results showed that these vectors exhibited
      higher efficiency than the former vector pPSC-G carrying exogenous regulators,
      and the vector pRFA with Prrn, psbA-5'RE, and TpsbA showed the highest
      efficiency. This research provides a set of effective endogenous regulators for
      T. subcordiformis and will facilitate future fundamental studies of this alga.

PMID- 27038954
TI  - An extremely alkaline mannanase from Streptomyces sp. CS428 hydrolyzes
      galactomannan producing series of mannooligosaccharides.
AB  - An alkaline-thermostable mannanase from Streptomyces sp. CS428 was produced,
      purified, and biochemically characterized. The extracellular mannanase (Mn428)
      was purified to homogeneity with 12.4 fold, specific activity of 2406.7 U/mg, and
      final recovery of 37.6 %. The purified beta-mannanase was found to be a monomeric
      protein with a molecular mass of approximately 35 kDa as analyzed by SDS-PAGE and
      zymography. The first N-terminal amino acid sequences of mannanase enzyme were
      HIRNGNHQLPTG. The optimal temperature and pH for enzyme were 60  degrees C and
      12.5, respectively. The mannanase activities were significantly affected by the
      presence of metal ions, modulators, and detergents. Km and Vmax values of Mn428
      were 1.01 +/- 3.4 mg/mL and 5029 +/- 85 umol/min mg, respectively when different
      concentrations (0.6-10 mg/mL) of locust bean gum galactomannan were used as
      substrate. The substrate specificity of enzyme showed its highest specificity
      towards galactomannan which was further hydrolyzed to produce mannose,
      mannobiose, mannotriose, and a series of mannooligosaccharides.
      Mannooligosaccharides can be further converted to ethanol production, thus the
      purified beta-mannanase isolated from Streptomyces sp. CS428 was found to be
      attractive for biotechnological applications.

PMID- 27038956
TI  - Ethanol production from acid- and alkali-pretreated corncob by endoglucanase and
      beta-glucosidase co-expressing Saccharomyces cerevisiae subject to the expression
      of heterologous genes and nutrition added.
AB  - Low-cost technologies to overcome the recalcitrance of cellulose are the key to
      widespread utilization of lignocellulosic biomass for ethanol production.
      Efficient enzymatic hydrolysis of cellulose requires the synergism of various
      cellulases, and the ratios of each cellulase are required to be regulated to
      achieve the maximum hydrolysis. On the other hand, engineering of cellulolytic
      Saccharomyces cerevisiae strains is a promising strategy for lignocellulosic
      ethanol production. The expression of cellulase-encoding genes in yeast would
      affect the synergism of cellulases and thus the fermentation ability of strains
      with exogenous enzyme addition. However, such researches are rarely reported. In
      this study, ten endoglucanase and beta-glucosidase co-expressing S. cerevisiae
      strains were constructed and evaluated by enzyme assay and fermentation
      performance measurement. The results showed that: (1) maximum ethanol titers of
      recombinant strains exhibited high variability in YPSC medium (20 g/l peptone, 10
      g/l yeast extract, 100 g/l acid- and alkali-pretreated corncob) within 10 days.
      However, they had relatively little difference in USC medium (100 g/l acid- and
      alkali-pretreated corncob, 0.33 g/l urea, pH 5.0). (2) Strains 17# and 19#, with
      ratio (CMCase to beta-glucosidase) of 7.04 +/- 0.61 and 7.40 +/- 0.71
      respectively, had the highest fermentation performance in YPSC. However, strains
      11# and 3# with the highest titers in USC medium had a higher ratio of CMCase to
      beta-glucosidase, and CMCase activities. These results indicated that nutrition,
      enzyme activities and the ratio of heterologous enzymes had notable influence on
      the fermentation ability of cellulase-expressing yeast.

PMID- 27038955
TI  - Comparison of the abundance and community structure of ammonia oxidizing
      prokaryotes in rice rhizosphere under three different irrigation cultivation
      modes.
AB  - The abundance, diversity and community structure of ammonia oxidizing archaea
      (AOA) and bacteria (AOB) in rice rhizosphere soils under three different
      irrigation cultivated modes, named continuous irrigation mode (C), intermittent
      irrigation mode (I) and semi-arid mode (M), respectively, were investigated using
      amoA gene as a molecular biomarker. Clone libraries and quantitative polymerase
      chain reaction results indicated the highest number of archaeal amoA gene copy
      was detected in M cultivation mode, then in I and C, whereas, their order of amoA
      gene copy numbers were I > M > C for AOB, and those were obvious higher than in
      the bulk soil. The ratios of AOA/AOB were greater than 1 for all samples,
      suggested the predominance of AOA throughout the period of rice growth in the
      three different irrigation cultivation modes. Diversity index (SChao1 and Shannon
      H) have an obvious variation in three different irrigation cultivation modes. For
      AOA, SChao1 was highest in M and lowest in I mode, whereas, Shannon H was highest
      in M cultivation mode and lowest in C mode. For AOB, mode M exhibited the highest
      diversity index (SChao1 and Shannon H), while C showed the lowest highest
      diversity, suggested long-term water input (continuous mode) may decrease
      diversity of ammonia oxidizers, whereas mode M may be more appropriate for them.
      In addition, AOA sequences fall within Nitrososphaera, Nitrosopumilus and
      Nitrosotalea cluster with proportion of 89.38, 8.85 and 1.77 %, respectively. AOB
      gene sequences belonged to the Nitrosomonas and Nitrosospira genera with
      proportion of 90.97 and 9.03 %, respectively. In addition, the abundances,
      diversity and community structure had an obvious temporal variation in three
      developmental stages of rice, further suggested rice growth obviously affected
      the ammonia oxidizing prokaryotes in their rhizosphere soil.

PMID- 27038957
TI  - Functional food red yeast rice (RYR) for metabolic syndrome amelioration: a
      review on pros and cons.
AB  - Red yeast rice (RYR), the fermentation product of mold Monascus purpureus has
      been an integral part of Oriental food and traditional Chinese medicine, long
      before the discovery of their medicinal roles. With the identification of
      bioactive components as polyketide pigments (statins), and unsaturated fatty
      acids, RYR has gained a nutraceutical status. Hypercholesterolemic effect of this
      fermented compound has been validated and monacolin K has been recognized as the
      pivotal component in cholesterol alleviation. Functional similarity with
      commercial drug lovastatin sans the side effects has catapulted its popularity in
      other parts of the world as well. Apart from the hypotensive role, ameliorative
      benefits of RYR as anti-inflammatory, antidiabetic, anticancer and osteogenic
      agent have emerged, fueling intense research on it. Mechanistic studies have
      revealed their interaction with functional agents like coenzyme Q10, astaxanthin,
      vitamin D, folic acid, policosanol, and berberine. On the other hand, concurrence
      of mycotoxin citrinin and variable content of statin has marred its integration
      in mainstream medication. In this disputable scenario, evaluation of the scopes
      and lacunae to overcome seems to contribute to an eminent area of healthcare. Red
      yeast rice (RYR), the rice-based fermentation product of mold Monascus purpureus
      is a functional food. Its bioactive component monacolin K acts like synthetic
      drug lovastatin, without the severe side effects of the latter. RYR has been
      validated to lower cholesterol, control high blood pressure; confer anti
      flammation, hypoglycaemic, anticancer and osteogenic properties. However, dose
      inconsistency and co-occurrence of toxin citrinin hampers its dietary
      supplementation prospect. Further research might facilitate development of RYR as
      a nutraceutical.

PMID- 27038958
TI  - Microorganisms as efficient biosystem for the synthesis of metal nanoparticles:
      current scenario and future possibilities.
AB  - Nanoparticles, the elementary structures of nanotechnology, are important
      materials for fundamental studies and variety of applications. The different
      sizes and shapes of these materials exhibit unique physical and chemical
      properties than their bulk materials. There is a great interest in obtaining well
      dispersed, ultrafine, and uniform nanoparticles to delineate and utilize their
      distinct properties. Nanoparticle synthesis can be achieved through a wide range
      of materials utilizing a number of methods including physical, chemical, and
      biological processes with various precursors from liquids and solids. There is a
      growing need to prepare environmentally friendly nanoparticles that do not
      produce toxic wastes in their process synthesis protocol. This kind of synthesis
      can be achieved by green environment benign processes, which happen to be mostly
      of a biological nature. Microorganisms are one of the most attractive and simple
      sources for the synthesis of different types of nanoparticles. This review is an
      attempt to provide the up-to-date information on current status of nanoparticle
      synthesis by different types of microorganisms such as fungi, yeast, bacteria,
      cyanobacteria, actinomycete, and algae. The probable biosynthesis mechanism and
      conditions for size/shape control are described. Various applications of
      microbially synthesized nanoparticles are summarized. They include antibacterial,
      antifungal, anticancer, larvicidal, medical imaging, biosensor, and catalytic
      applications. Finally, limitations and future prospects for specific research are
      discussed. 

PMID- 27038959
TI  - Identification of major cardiovascular events in patients with diabetes using
      primary care data.
AB  - BACKGROUND: Routine primary care data are increasingly being used for evaluation
      and research purposes but there are concerns about the completeness and accuracy
      of diagnoses and events captured in such databases. We evaluated how well
      patients with major cardiovascular disease (CVD) can be identified using primary
      care morbidity data and drug prescriptions. METHODS: The study was conducted
      using data from 17,230 diabetes patients of the GIANTT database and Dutch
      Hospital Data register. To estimate the accuracy of the different measures, we
      analyzed the sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) relative to hospitalizations and/or records with
      a diagnosis indicating major CVD, including ischaemic heart diseases and
      cerebrovascular events. RESULTS: Using primary care morbidity data, 43% of major
      CVD hospitalizations could be identified. Adding drug prescriptions to the search
      increased the sensitivity up to 94%. A proxy of at least one prescription of
      either a platelet aggregation inhibitor, vitamin k antagonist or nitrate could
      identify 85% of patients with a history of major CVD recorded in primary care,
      with an NPV of 97%. Using the same proxy, 57% of incident major CVD recorded in
      primary or hospital care could be identified, with an NPV of 99%. CONCLUSIONS: A
      substantial proportion of major CVD hospitalizations was not recorded in primary
      care morbidity data. Drug prescriptions can be used in addition to diagnosis
      codes to identify more patients with major CVD, and also to identify patients
      without a history of major CVD.

PMID- 27038960
TI  - Promoting and Providing HPV Vaccination in Hawaii: Barriers Faced by Health
      Providers.
AB  - Despite the availability of HPV prophylactic vaccines, uptake has been suboptimal
      in the US. In the state of Hawaii, HPV vaccine coverage has decreased among
      females and remains low among males aged 13-17. The reasons for low uptake are
      unknown and may indicate the existence of critical barriers to HPV vaccination.
      The purpose of this investigation was to identify policy, system and
      environmental barriers and promoters of pediatric HPV vaccination in Hawaii. An
      online 86-item survey addressing knowledge, attitudes, beliefs, practices, and
      barriers to HPV vaccination was distributed to practicing physicians in Hawaii
      specializing in Pediatrics, Family Medicine, and Obstetrics-Gynecology. Survey
      responses were received from a total of 120 physicians. Private practice
      physicians reported more concerns with vaccine ordering and stocking costs (p <
      0.0001), reimbursement levels (p < 0.0001), and insurance coverage (p < 0.0001)
      compared to physicians in large group practices. Eighty-three percent of
      providers cited lack of parent knowledge and understanding of HPV infection as a
      barrier. Over half of physicians (58 %) reported that completion of the 3-dose
      schedule was a barrier. Most physicians did not use tracking or reminder systems
      to ensure dose completion. A majority (58 %) of providers cited the lack of
      school-based vaccination requirements as a barrier. Uptake of HPV vaccination in
      Hawaii may be impeded by physician perception of parent knowledge and attitudes.
      Cost-related system barriers are particular barriers among those in private
      practice. Completion of the 3-dose schedule also remains a challenge.

PMID- 27038961
TI  - Construct validity of a video-tracking system based on orthogonal cameras
      approach for objective assessment of laparoscopic skills.
AB  - PURPOSE: This study was aimed to establish the construct validity of a video
      tracking system based on orthogonal cameras approach for assessment of
      laparoscopic psychomotor skills in training environments. METHODS: The camera
      tracking system consists of two webcams placed in orthogonal configuration at a
      distance of 13.5 cm. The orthogonal cameras employ a color segmentation algorithm
      to register the 3D motions of the laparoscopic instruments using colored tapes
      placed on the distal end. For construct validity, 31 participants (4 experts and
      27 residents) performed three training tasks in a laparoscopic box trainer with
      the built-in orthogonal cameras system. Eleven motion-related parameters were
      used to evaluate their performance. Statistical analysis was performed, and
      results between two groups were compared using a Mann-Whitney U-test. RESULTS:
      Construct validity results showed statistical differences in almost all motion
      related parameters for assessment of laparoscopic technical skills. Results
      demonstrated that the orthogonal video-based tracking system was able to
      differentiate laparoscopic experience between experts and trainees surgeons.
      CONCLUSION: The orthogonal cameras system was successfully validated in a
      laparoscopic box trainer. This video-based tracking system was able to
      distinguish performance between experts and trainees surgeons, showing its
      potential as a reliable tool to assess laparoscopic psychomotor skills. The
      orthogonal cameras allow incorporating the advantages of this video motion
      tracking technology with the benefits of the traditional laparoscopic box
      trainers, creating realistic haptic feedback and allowing the evaluation of
      psychomotor skills of the surgeons.

PMID- 27038962
TI  - Three-dimensional quantitative assessment of ablation margins based on
      registration of pre- and post-procedural MRI and distance map.
AB  - PURPOSE: Contrast-enhanced MR images are widely used to confirm the adequacy of
      ablation margin after liver ablation for early prediction of local recurrence.
      However, quantitative assessment of the ablation margin by comparing pre- and
      post-procedural images remains challenging. We developed and tested a novel
      method for three-dimensional quantitative assessment of ablation margin based on
      non-rigid image registration and 3D distance map. METHODS: Our method was tested
      with pre- and post-procedural MR images acquired in 21 patients who underwent
      image-guided percutaneous liver ablation. The two images were co-registered using
      non-rigid intensity-based registration. After the tumor and ablation volumes were
      segmented, target volume coverage, percent of tumor coverage, and Dice similarity
      coefficient were calculated as metrics representing overall adequacy of ablation.
      In addition, 3D distance map around the tumor was computed and superimposed on
      the ablation volume to identify the area with insufficient margins. For patients
      with local recurrences, the follow-up images were registered to the post
      procedural image. Three-dimensional minimum distance between the recurrence and
      the areas with insufficient margins was quantified. RESULTS: The percent tumor
      coverage for all nonrecurrent cases was 100 %. Five cases had tumor recurrences,
      and the 3D distance map revealed insufficient tumor coverage or a 0-mm margin. It
      also showed that two recurrences were remote to the insufficient margin.
      CONCLUSIONS: Non-rigid registration and 3D distance map allow us to
      quantitatively evaluate the adequacy of the ablation margin after percutaneous
      liver ablation. The method may be useful to predict local recurrences immediately
      following ablation procedure.

PMID- 27038963
TI  - Combined 2D and 3D tracking of surgical instruments for minimally invasive and
      robotic-assisted surgery.
AB  - PURPOSE: Computer-assisted interventions for enhanced minimally invasive surgery
      (MIS) require tracking of the surgical instruments. Instrument tracking is a
      challenging problem in both conventional and robotic-assisted MIS, but vision
      based approaches are a promising solution with minimal hardware integration
      requirements. However, vision-based methods suffer from drift, and in the case of
      occlusions, shadows and fast motion, they can be subject to complete tracking
      failure. METHODS: In this paper, we develop a 2D tracker based on a Generalized
      Hough Transform using SIFT features which can both handle complex environmental
      changes and recover from tracking failure. We use this to initialize a 3D tracker
      at each frame which enables us to recover 3D instrument pose over long sequences
      and even during occlusions. RESULTS: We quantitatively validate our method in 2D
      and 3D with ex vivo data collected from a DVRK controller as well as providing
      qualitative validation on robotic-assisted in vivo data. CONCLUSIONS: We
      demonstrate from our extended sequences that our method provides drift-free
      robust and accurate tracking. Our occlusion-based sequences additionally
      demonstrate that our method can recover from occlusion-based failure. In both
      cases, we show an improvement over using 3D tracking alone suggesting that
      combining 2D and 3D tracking is a promising solution to challenges in surgical
      instrument tracking.

PMID- 27038964
TI  - Virtually transparent surgical instruments in endoscopic surgery with
      augmentation of obscured regions.
AB  - PURPOSE: We developed and evaluated a visual compensation system that allows
      surgeons to visualize obscured regions in real time, such that the surgical
      instrument appears virtually transparent. METHODS: The system consists of two
      endoscopes: a main endoscope to observe the surgical environment, and a
      supporting endoscope to render the region hidden from view by surgical
      instruments. The view captured by the supporting endoscope is transformed to
      simulate the view from the main endoscope, segmented to the shape of the hidden
      regions, and superimposed to the main endoscope image so that the surgical
      instruments look transparent. A prototype device was benchmarked for processing
      time and superimposition rendering error. Then, it was evaluated in a training
      environment with 22 participants performing a backhand needle driving task with
      needle exit point error as the criterion. Lastly, we conducted an in vivo study.
      RESULTS: In the benchmark, the mean processing time was 62.4 ms, which was lower
      than the processing time accepted in remote surgeries. The mean superimposition
      error of the superimposed image was 1.4 mm. In the training environment, needle
      exit point error with the system decreased significantly for experts compared
      with the condition without the system. This change was not significant for
      novices. In the in vivo study, our prototype enabled visualization of needle exit
      points during anastomosis. CONCLUSION: The benchmark suggests that the
      implemented system had an acceptable performance, and evaluation in the training
      environment demonstrated improved surgical task outcomes in expert surgeons. We
      will conduct a more comprehensive in vivo study in the future.

PMID- 27038965
TI  - Fully automatic reconstruction of personalized 3D volumes of the proximal femur
      from 2D X-ray images.
AB  - PURPOSE: Accurate preoperative planning is crucial for the outcome of total hip
      arthroplasty. Recently, 2D pelvic X-ray radiographs have been replaced by 3D CT.
      However, CT suffers from relatively high radiation dosage and cost. An
      alternative is to reconstruct a 3D patient-specific volume data from 2D X-ray
      images. METHODS: In this paper, based on a fully automatic image segmentation
      algorithm, we propose a new control point-based 2D-3D registration approach for a
      deformable registration of a 3D volumetric template to a limited number of 2D
      calibrated X-ray images and show its application to personalized reconstruction
      of 3D volumes of the proximal femur. The 2D-3D registration is done with a
      hierarchical two-stage strategy: the scaled-rigid 2D-3D registration stage
      followed by a regularized deformable B-spline 2D-3D registration stage. In both
      stages, a set of control points with uniform spacing are placed over the domain
      of the 3D volumetric template first. The registration is then driven by computing
      updated positions of these control points with intensity-based 2D-2D image
      registrations of the input X-ray images with the associated digitally
      reconstructed radiographs, which allows computing the associated registration
      transformation at each stage. RESULTS: Evaluated on datasets of 44 patients, our
      method achieved an overall surface reconstruction accuracy of [Formula: see text]
      and an average Dice coefficient of [Formula: see text]. We further investigated
      the cortical bone region reconstruction accuracy, which is important for planning
      cementless total hip arthroplasty. An average cortical bone region Dice
      coefficient of [Formula: see text] and an inner cortical bone surface
      reconstruction accuracy of [Formula: see text] were found. CONCLUSIONS: In
      summary, we developed a new approach for reconstruction of 3D personalized
      volumes of the proximal femur from 2D X-ray images. Comprehensive experiments
      demonstrated the efficacy of the present approach.

PMID- 27038966
TI  - Guided ultrasound calibration: where, how, and how many calibration fiducials.
AB  - PURPOSE: Many image-guided interventions rely on tracked ultrasound where the
      transducer is augmented with a tracking device. The relationship between the
      ultrasound image coordinate system and the tracking sensor must be determined
      accurately via probe calibration. We introduce a novel calibration framework
      guided by the prediction of target registration error (TRE): Between successive
      measurements of the calibration phantom, our framework guides the user in
      choosing the pose of the calibration phantom by optimizing TRE. METHODS: We
      introduced an oriented line calibration phantom and modeled the ultrasound
      calibration process as a point-to-line registration problem. We then derived a
      spatial stiffness model of point-to-line registration for estimating TRE
      magnitude at any target. Assuming isotropic, identical localization error, we
      used the model to estimate TRE for each pixel using the current calibration
      estimate. We then searched through the calibration tool space to find the pose
      for the next fiducial which maximally minimized TRE. RESULTS: Both simulation and
      experimental results suggested that TRE decreases monotonically, reaching an
      asymptote when a sufficient number of measurements (typically around 12) are
      made. Independent point reconstruction accuracy assessment showed sub-millimeter
      accuracy of the calibration framework. CONCLUSION: We have introduced the first
      TRE-guided ultrasound calibration framework. Using a hollow straw as an oriented
      line phantom, we virtually constructed a rigid lines phantom and modeled the
      calibration process as a point-to-line registration. Highly accurate calibration
      was achieved with minimal measurements by using a spatial stiffness model of TRE
      to strategically choose the pose of the calibration phantom between successive
      measurements.

PMID- 27038967
TI  - Real-time 6DoF pose recovery from X-ray images using library-based DRR and hybrid
      optimization.
AB  - PURPOSE: Real-time 6 degrees of freedom (6DoF) pose recovery and tracking from X
      ray images is a key enabling technology for many interventional imaging
      applications. However, real-time 2D/3D registration is a very challenging problem
      because of the heavy computation in iterative digitally reconstructed radiograph
      (DRR) generation. In this paper, we propose a real-time 2D/3D registration
      framework using library-based DRRs to achieve high computational efficiency.
      METHOD: The proposed method pre-computes a library of canonical DRRs and
      reconstructs library-based DRRs (libDRRs) during registration without online
      rendering. The transformation parameters are decoupled to 2 geometry-relevant and
      4 geometry-irrelevant ones so that canonical DRRs only need to cover the
      variation of 2 geometry-relevant parameters, making it practical to be pre
      computed and stored. The 2D/3D registration using libDRRs is then solved as a
      hybrid optimization problem, i.e., continuous in geometry-irrelevant parameters
      while discrete in geometry-relevant parameters. RESULTS: On 5 fluoroscopic
      sequences with 246 frames acquired during animal studies with a transesophageal
      echocardiography (TEE) probe in the field of view, 6DoF tracking of the TEE probe
      using the proposed method achieved a mean target registration error in the
      projection direction (mTREproj) of 0.81 mm, a success rate of 100 % (defined as
      mTREproj [Formula: see text]2.5 mm), and a registration frame rate of 23.1 fps on
      a pure CPU-based implementation executed in a single thread. CONCLUSION: Using
      libDRRs with a hybrid optimization can significantly improve the computational
      efficiency (up to tenfold) for 6DoF pose recovery and tracking with little
      degradation in robustness and accuracy, compared to conventional intensity-based
      2D/3D registration using ray casting DRRs with a continuous optimization.

PMID- 27038968
TI  - Role of Alternative Therapies for Chronic Pain Syndromes.
AB  - There is increasing interest in the use of complimentary and alternative medicine
      (CAM) for the treatment of chronic pain. This review examines alternative and
      complimentary therapies, which can be incorporated as part of a biopsychosocial
      approach in the treatment of chronic pain syndromes. In the present
      investigation, literature from articles indexed on PubMed was evaluated including
      topics of alternative therapies, complimentary therapies, pain psychology,
      biofeedback therapy, physical exercise therapies, acupuncture, natural and herbal
      supplements, whole-body cryotherapy, and smartphone technologies in the treatment
      of chronic pain syndromes. This review highlights the key role of psychology in
      the treatment of chronic pain. Cognitive behavior therapy appears to be the most
      impactful while biofeedback therapy has also been shown to be effective for
      chronic pain. Exercise therapy has been shown to be effective in short-,
      intermediate-, and long-term pain states. When compared to that in sham controls,
      acupuncture has shown some benefit for neck pain immediately after the procedure
      and in the short term and improvement has also been demonstrated in the treatment
      of headaches. The role of smartphones and whole-body cryotherapy are new
      modalities and further studies are needed. Recent literature suggests that
      several alternate therapies could play a role in the treatment of chronic pain,
      supporting the biopsychosocial model in the treatment of pain states. 

PMID- 27038969
TI  - Ice Pick Headache.
AB  - Ice pick headache, also called idiopathic or primary stabbing headache, is a
      unique headache type associated with ultra-brief stabs of pain, most commonly in
      the frontal or temporal area. It occurs predominantly in women and is estimated
      to affect 2-35% of the population. Unlike other headache types of short duration,
      such as short-lasting unilateral neuralgiform headache with conjunctival
      injection and tearing (SUNCT), ice pick headache is not associated with any
      cranial autonomic symptoms but has been known to occur with nausea, vomiting,
      photophobia, and dizziness. It exists in two forms: primary and secondary, with
      examples of secondary causes being herpes zoster meningoencephalitis,
      meningiomas, stroke, and multiple sclerosis. Ice pick headache is one of the
      "indomethacin responsive headaches," but up to 35% of patients fail to show
      significant benefit with that treatment. Other treatment options include
      gabapentin, cyclooxygenase-2 inhibitors, melatonin, and external hand warming.

PMID- 27038970
TI  - The Link Between Infantile Colic and Migraine.
AB  - Infantile colic is a self-limiting disorder of excessive infant crying or
      fussiness that peaks at 6 weeks of age and typically improves by 3 months of age.
      The etiology of infantile colic has yet to be definitively elucidated, but there
      is increasing research to support its relationship to migraine. The aims of this
      review are to present recent research investigating the connection between
      infantile colic and migraine. The importance of identifying this connection is
      useful in reducing invasive and potentially harmful investigations and to
      identify age appropriate pharmacologic interventions that would be safe in this
      population.

PMID- 27038971
TI  - No Laughing Matter: Gelastic Migraine and Other Unusual Headache Syndromes.
AB  - Primary and secondary headache disorders have established diagnostic criteria in
      the International Classification of Headache Disorders IIIb, as well as classic
      findings, which although not part of the formal criteria are often suggestive of
      a particular diagnosis. At times, headache disorders can involve unusual symptoms
      that lack an identifiable secondary cause. This review will discuss some of these
      unusual symptoms, including headache associated auditory and olfactory symptoms,
      as well as two case reports involving gelastic migraine and migrainous
      thoracalgia. 

PMID- 27038972
TI  - New Chronic Pain Treatments in the Outpatient Setting: Review Article.
AB  - Chronic pain is an issue encountered by many health care providers in their
      routine clinical practice. In addition to generalized patient suffering, this
      condition has significant clinical, psychological, and socioeconomic impact due
      to its widespread occurrence. The landscape of chronic pain management has been
      changing rapidly with an array of treatment innovations, better understanding of
      established therapies, and care coordination across specialties. In this article,
      we have reviewed emerging new modalities as well as transformation of established
      therapies by interventional, pharmacologic, rehabilitative, psychological,
      complimentary, and interdisciplinary approaches. 

PMID- 27038973
TI  - International note: Maternal warmth, behavioral control, and psychological
      control: Relations to adjustment of Ghanaian early adolescents.
AB  - This investigation addressed the relation between maternal warmth, behavioral
      control, psychological control, and psychological adjustment in a sample of 119
      Ghanaian adolescents (42% boys) living in an urban area (mean age = 14.19).
      Adolescents in the sample reported clinically elevated levels of depression and
      anxiety. Significant associations were found between warmth, behavioral control,
      and psychological control and adolescents' anxiety, physical aggression,
      relational aggression, positive friendship quality, and conflict with friends.
      Warmth moderated the effect of behavioral control on anxiety, physical
      aggression, and relational aggression such that higher levels of warmth in
      combination with higher levels of behavioral control were related to more
      positive adjustment. Higher levels of warmth in conjunction with higher
      psychological control were related to higher levels of anxiety. Boys who reported
      lower levels of warmth in combination with higher behavioral control reported
      higher levels of physical aggression. For boys reporting higher levels of warmth,
      higher behavioral control was associated with lower physical aggression.

PMID- 27038974
TI  - Mental health benefits of outdoor adventures: Results from two pilot studies.
AB  - This paper investigates potential mental health benefits of outdoor and adventure
      education programs. It is argued that experiences made in successful programs can
      increase self-efficacy, mindfulness and subjective well-being. Furthermore,
      programs may reduce feelings of time pressure and mental stress amongst
      participants. Evidence comes from two pilot studies: In the school project
      "Crossing the Alps" (Study 1), 14-year-old participants reported an increase in
      life satisfaction, mindfulness and a decrease in the PSQ Subscale 'demand' after
      a successful nine-day hike through the German, Austrian, and Italian Alps. In the
      university project "Friluftsliv" (Study 2) participants scored higher in life
      satisfaction, happiness, mindfulness, and self-efficacy and lower in perceived
      stress after having spent eight days in the wilderness of the Norwegian
      Hardangervidda region, miles away from the next locality. The findings suggest
      that outdoor education and wilderness programs can foster mental health in youths
      and young adults.

PMID- 27038975
TI  - ISS 2015 Annual meeting Maui, HI: scientific paper presentations.

PMID- 27038976
TI  - Lumps in the thigh. Mazabraud Syndrome.

PMID- 27038977
TI  - Protocol of the Stroke in Korean Young Adults Study: A Multicenter Case-Control
      Study and Prospective Cohort Study.
AB  - BACKGROUND: The incidence of ischemic stroke in young adults has been rising over
      recent decades, but there is still limited information on its risk factors,
      etiologies, and outcomes. Because these patients generally participate in social
      life, risk factors associated with lifestyle may have a great impact and need to
      be identified. METHODS: The SKY (Stroke in Korean Young Adults) study is a
      multicenter case-control study and a prospective cohort study in 8 tertiary
      medical centers in the Republic of Korea. The case subjects are patients aged 18
      44 years with first-ever ischemic stroke occurring within 1 month of stroke
      onset, and the control subjects are age- and gender-matched community controls.
      Our aim is to include 470 cases and 470 controls. The main objective of our study
      is to determine the risk factors and the causes of ischemic stroke in Korean
      young adults. Both well-documented risk factors and little-known lifestyle
      related risk factors such as lifestyle habits and psychological distress
      including job strain will be evaluated by comparing cases and controls using a
      structured questionnaire. Secondary objectives are to determine the risks of
      mortality, recurrent vascular events, and poststroke epilepsy in these patients.
      Conditional logistic regression analysis will be used to estimate odds ratios and
      95% confidence intervals. CONCLUSIONS: The SKY study is designed to obtain more
      insights into relatively little-known risk factors in young Korean adults with
      ischemic stroke. The results may also help identify the frequencies of uncommon
      etiologies and outcomes in these patients.

PMID- 27038978
TI  - Re: "Report of Dramatic Improvement after a Lumboperitoneal Shunt Procedure in a
      Case of Anticoagulation Therapy-Resistant Cerebral Venous Thrombosis".

PMID- 27038980
TI  - Average Temperature, Diurnal Temperature Variation, and Stroke Hospitalizations.
AB  - BACKGROUND: Studies assessing the relationship between meteorological factors and
      stroke incidence are inconsistent. We assessed the associations of average
      temperature and diurnal temperature fluctuations with ischemic stroke
      hospitalizations in a nationally representative sample of patients in the United
      States. METHODS: Hospitalizations were identified for adults aged 18 years or
      older in the 2009-2011 Nationwide Inpatient Sample and linked with county-level
      monthly average temperatures from the United States National Climatic Data
      Center. Logistic regression models assessed the relationships of 5 degrees F
      increases in average temperature and diurnal temperature variation (difference
      between high- and low-daily temperatures) with the odds of ischemic stroke
      hospitalization (International Classification of Diseases, Ninth Revision,
      Clinical Modification codes 433, 434, and 436), adjusting for patient
      characteristics and dew point. Models were stratified by age (18-64, >=65 years),
      season, and region, with analysis at the hospitalization level. RESULTS:
      Increased average temperature was associated with decreased odds of stroke
      hospitalization among both age groups and across seasons in the Northeast, and
      among the elderly in the West. Increased diurnal temperature variation was
      associated with increased odds of stroke hospitalization for nearly all regions
      in the spring to fall seasons; associations were most pronounced in the Northeast
      and strongest in the spring. CONCLUSIONS: Lower average temperature and larger
      diurnal temperature variations were associated with stroke hospitalizations.
      Associations were strongest in the Northeast and largely similar across seasons
      and age. Further research is needed to explore the mechanisms underlying these
      associations. Understanding these patterns may lead to targeted prevention
      strategies for vulnerable populations during periods of extreme weather
      conditions.

PMID- 27038979
TI  - Reversibility of White Matter Hyperintensity by Revascularization Surgery in
      Moyamoya Disease.
AB  - BACKGROUND: White matter lesions (WMLs) indicate progressive cerebral small
      vessel disease and are frequently observed in aging people and stroke patients.
      The purpose of this study was to evaluate WMLs and the influence of
      revascularization surgery for WMLs in patients with moyamoya disease. METHODS: A
      total of 42 hemispheres in 21 patients with moyamoya disease were included in
      this analysis. WMLs were detected on fluid-attenuated inversion recovery (FLAIR)
      imaging in 24 hemispheres. The distribution pattern of WMLs was categorized. WMLs
      were measured by manually creating a region of interest, and the total WML volume
      in the hemisphere was estimated and compared with the control group. Clinical
      features of patients with WMLs and postoperative changes were analyzed. RESULTS:
      The total WML volume in moyamoya disease was significantly higher than that of
      controls (P = .014). WMLs were observed in the internal watershed zone,
      especially in the watershed zone between the anterior cerebral artery and the
      middle cerebral artery. Patients with WMLs had significantly higher magnetic
      resonance angiography scores compared with controls (P = .015). A given patient's
      total WML volume per hemisphere was significantly decreased after surgery (P =
      .001). CONCLUSIONS: WMLs on FLAIR imaging increase in patients with moyamoya
      disease and are reversible by revascularization surgery. Improvement of cerebral
      blood flow is partly related to the decrease in WMLs. The present results provide
      insight into the potential role of revascularization surgery.

PMID- 27038981
TI  - Is Quasi-moyamoya Disease a Uniform Disease Entity? A Three-Dimensional
      Constructive Interference in Steady State Imaging Study.
AB  - BACKGROUND: Quasi-moyamoya disease (MMD) or moyamoya syndrome is based on various
      underlying diseases and radiologically simulates MMD, but its disease entity is
      still unclear. Recent studies have proven specific shrinkage of the involved
      arteries in MMD. Using 3-dimensional constructive interference in steady state
      (3D-CISS), therefore, this study aimed to analyze the outer diameter of the
      involved arteries in quasi-MMD. METHODS: This study included 9 patients with
      quasi-MMD (unilateral type, n = 2; bilateral type, n = 7). Using 3D-CISS, the
      outer diameter was quantified in the internal carotid artery distal to the
      posterior communicating artery (C1), the horizontal portion of the middle and
      anterior cerebral arteries (M1 and A1, respectively), and the basilar artery.
      Control values were obtained from 17 healthy subjects. RESULTS: In 7 of 9
      patients, the outer diameters of C1, M1, and A1 were significantly smaller than
      those of the controls. On the other hand, the values were normal in other 2
      patients. There was no significant difference in the underlying disorders between
      the 2 groups. All 3 pediatric patients are categorized into the arterial
      shrinkage group, but 2 of 6 adult patients were not. CONCLUSIONS: These findings
      strongly suggest that quasi-MMD is not a uniform disease entity and includes at
      least 2 pathophysiologically different groups: the arterial shrinkage group and
      the nonarterial shrinkage group. A certain subgroup of MMD patients may be
      misdiagnosed as quasi-MMD because of the patients' comorbid disorders and mixed
      up with the patients who present angiographic findings similar to MMD in spite of
      the lack of arterial shrinkage.

PMID- 27038982
TI  - Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal
      Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.
AB  - OBJECTIVE: To assess the relationship between individual nephrometry score (NS)
      constituents (RENAL) on perioperative outcomes and renal function of the surgical
      kidney in patients undergoing laparoscopic partial nephrectomy or robotic
      assisted partial nephrectomy. MATERIALS AND METHODS: Two hundred forty-five
      patients who underwent laparoscopic partial nephrectomy or robotic-assisted
      partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each
      renal mass' NS was calculated from preoperative computed tomography imaging.
      Multivariate regression analysis was used to evaluate the effect of NS variables
      on perioperative outcomes and change in overall renal function (as estimated by
      glomerular filtration rate) from preoperative to 1-year postoperative. A cohort
      analysis assessed the effect of NS variables on change in split renal function of
      the surgical kidney from pre- to postoperative based on nuclear medicine renal
      scintigraphy. RESULTS: Tumor radius (R), endophytic nature (E), and nearness to
      collecting system (N) variables significantly and incrementally predicted a
      longer operative time and warm ischemia time. Overall renal function based on
      glomerular filtration rate was not affected by any NS variable. However, percent
      function of the surgical kidney by renal scintigraphy significantly decreased
      postoperatively as R and E values increased. CONCLUSION: R, E, and N were
      associated with significant changes in warm ischemia time and operative time. R
      and E were associated with a significant decrease in split renal function of the
      surgical kidney at 1 year after surgery but not with overall renal function. R,
      E, and N are the NS constituents most relevant to perioperative outcomes and
      postoperative differential renal function after partial nephrectomy.

PMID- 27038983
TI  - Giant Angiofibroma of the Scrotum in a Child.
AB  - We present a unique case of angiofibroma of the scrotum in a 3-year-old child. A
      previous red plaque has been observed in the same region since the neonatal
      period. The boy underwent total excision of the mass. We suggest a close follow
      up of any erythematous lesion of the genital region; in case of rapid increase,
      it is important to proceed to prompt surgical excision. 

PMID- 27038984
TI  - Quantification of Long-term Stability and Specific Relief of Lower Urinary Tract
      Symptoms (LUTS) After Robot-assisted Radical Prostatectomy.
AB  - OBJECTIVE: To assist in preoperative counseling by assessing long-term changes in
      American Urological Association symptom scores (AUAss) and lower urinary tract
      symptom (LUTS)-related quality of life (QOL) in patients undergoing robot
      assisted radical prostatectomy (RARP). MATERIALS AND METHODS: RARP was performed
      on 666 men by one surgeon from 2002 to 2007 at a single institution. AUAss and
      QOL were queried preoperatively and at 3, 9, 15, 24-48, 60-84, and 96+ months
      postoperatively. LUTS subgroups were compared pre-/postsurgery using univariate
      and multivariate statistics. RESULTS: The mean and median follow-up for all
      responders was 3.0 and 2.4 years. Pad-free continence at 12 months was 89%. A
      subset of 174 men reported preoperative and long-term responses; average follow
      up was 5.8 years (range 4.0-10.3 years). AUAss for all men declined from baseline
      to 5 years by 3.7 (8.6 to 4.8) whereas QOL/Bother scores decreased by 0.5 (1.7 to
      1.2) (all P < .05). Men with baseline mild LUTS remained clinically unchanged
      with long-term AUAss. Individuals with moderate and severe preoperative LUTS had
      marked improvements in AUA and QOL scores (all P <= .05). CONCLUSION: Men with
      mild LUTS have short-term increases in AUAss but most return to baseline and are
      stable at 5 years. Benefits were found for men with preoperative moderate and
      severe LUTS in that 63% had significant QOL improvements and 68% reduced their
      AUAss to mild LUTS, persisting years after RARP. This study suggests that certain
      patients with preoperative urinary symptoms and bother may experience
      improvements in LUTS and associated QOL after RARP.

PMID- 27038985
TI  - Non-cystoscopic Removal of Retained Ureteral Stents With Mild Sedation in
      Children.
AB  - INTRODUCTION: We present a novel noncyctoscopic procedure in removing retained
      ureteral stents that requires minimal sedation and significantly reduces
      operation time and costs compared to the cystoscopy-based procedure. TECHNICAL
      CONSIDERATIONS: We used a simple self-made device, which was made of an Fr5
      feeding tube and a monofilament suture to remove the stents. Although the success
      rate is very high with this new procedure, it is important to point out that
      approximately 13% of our patients required 2 to 3 trials to remove the stents.
      Another potential problem is that the feeding tube may tie a knot when it is in
      the bladder, which could pose a risk of urethral injury when the knot is pulled
      out. CONCLUSION: The noncystoscopic procedure we have established has less
      operation time and costs less. This procedure provides an alternative solution in
      removing retained ureteral stents in child patients compared to conventional
      cystoscopy-based procedure.

PMID- 27038986
TI  - Description of the Terrestrial Larva of Parosca latipalpis (Macquart) (Diptera:
      Tabanidae) from Southern Chile.
AB  - The terrestrial larva of the austral horsefly, Parosca latipalpis (Macquart),
      identified by molecular techniques, is described. The larva of P. latipalpis
      resembles Scaptia auriflua (Donovan), Copidapha vicina (Taylor), Myioscaptia
      muscula (English), and Osca lata (Guerin-Meneville) in many morphological
      characters, as well as in their terrestrial habitats. Some characters that are
      shared between these species are unique among Tabanidae and provide evidence of
      their monophyletic origin, suggesting a typical Gondwanaland group. Larvae of P.
      latipalpis were found 2-3 cm below of the soil surface and associated with larvae
      of Coleoptera, Lepidoptera, and Diptera in southern Chile.

PMID- 27038987
TI  - Effects of losartan treatment on the physicochemical properties of diabetic rat
      bone.
AB  - Inhibitors of the renin-angiotensin system used to treat several diseases have
      also been shown to be effective on bone tissue, suggesting that angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers may reduce
      fracture risk. The present study investigated the effects of losartan on the
      physicochemical and biomechanical properties of diabetic rat bone. Losartan (5
      mg/kg/day) was administered via oral gavage for 12 weeks. Bone mineral density
      (BMD) was measured using dual-energy X-ray absorptiometry. Whole femurs were
      tested under tension to evaluate the biomechanical properties of bone. The
      physicochemical properties of bone were analyzed by Fourier transform infrared
      spectroscopy. Although losartan did not recover decreases in the BMD of diabetic
      bone, it recovered the physicochemical (mineral and collagen matrix) properties
      of diabetic rat bone. Furthermore, losartan also recovered ultimate tensile
      strength of diabetic rat femurs. Losartan, an angiotensin II type 1 receptor
      blocker, has a therapeutic effect on the physicochemical properties of diabetic
      bone resulting in improvement of bone strength at the material level. Therefore,
      specific inhibition of this pathway at the receptor level shows potential as a
      therapeutic target for diabetic patients suffering from bone diseases such as
      osteopenia.

PMID- 27038988
TI  - The natural history and hip geometric changes of primary hyperparathyroidism
      without parathyroid surgery.
AB  - There have been few reports on changes in bone geometry in asymptomatic patients
      with primary hyperparathyroidism (PHPT) not treated surgically. We reviewed the
      records concerning biochemical parameters, bone mineral density (BMD), and hip
      geometry in 119 PHPT patients who did not undergo parathyroidectomy, followed up
      at one of three hospitals affiliated to Seoul National University from 1997 to
      2013. We examined biochemical parameters over 7 years and BMD and hip geometry
      over 5 years of follow-up. We further compared hip geometry and BMD derived from
      dual-energy X-ray absorptiometry (DXA) between patients and age- and sex-matched
      controls. The median follow-up duration of 56 patients for whom surgery was not
      indicated was 33.9 months (range 11.2-131.2 months), and 19.6 % of these patients
      had disease progression during follow-up. Serum calcium levels remained stable
      for 7 years in all 119 patients. From a comparison of the PHPT patients for whom
      surgery was not indicated with controls, both male and postmenopausal female
      patients had significantly lower hip axis length (P < 0.001), cross-sectional
      moment of inertia (P < 0.001), cross-sectional area (P < 0.001), and section
      modulus (P < 0.001). In addition, cortical thickness was significantly decreased
      at 5 years compared with individual baseline values (P = 0.003). However, there
      was no significant change in BMD for the duration of the 5-year follow-up. DXA
      derived geometry can detect skeletal change in asymptomatic PHPT patients for
      whom surgery is not indicated, supporting the concept that even mild PHPT can
      eventually compromise the cortical bones. Hip geometry is a potential tool for
      monitoring skeletal complication in asymptomatic PHPT patients.

PMID- 27038989
TI  - The association between osteoporotic hip fractures and actinic lesions as a
      biomarker for cumulative sun exposure in older people-a retrospective case
      control study in Argentina.
AB  - The aim of this study was to analyze the association between the presence of
      actinic lesions (solar keratosis and non-melanoma skin cancer) and osteoporotic
      hip fractures in older patients. Both pathologies are common conditions in this
      age group. Since cumulative sun exposure is difficult to quantify, the presence
      of actinic lesions can be used to indirectly analyze the association between
      ultraviolet radiation and osteoporotic hip fractures. This was an observational
      case-control study. We reviewed the centralized medical records of patients with
      hip fracture (cases, n = 51) and patients with other diseases hospitalized in the
      same institution and period (controls, n = 59). The mean age of the patients was
      80 +/- 8.3 years (range 50-103 years). Differences in maternal hip fracture
      history were found between cases and controls (14.8 and 8 %, respectively; p =
      0.047). Falls history in the past year was higher in cases than in controls (p <
      0.0001). Actinic lesions were observed in 32.7 % of patients (prevalence rate
      23.5 % in cases, 40.7 % in controls; p = 0.04). When considering patients with
      actinic lesions, controls have a higher FRAX score compared with cases. Although
      sun exposure is recommended for bone health, it represents a risk factor for
      actinic lesions. The presence of actinic lesions may indicate a lower
      osteoporotic hip fracture risk. A balance between adequate lifetime sun exposure
      and protection against its adverse effects is required for each patient, in the
      context of geographic location.

PMID- 27038990
TI  - Generation and characterization of two immortalized human osteoblastic cell lines
      useful for epigenetic studies.
AB  - Different model systems using osteoblastic cell lines have been developed to help
      understand the process of bone formation. Here, we report the establishment of
      two human osteoblastic cell lines obtained from primary cultures upon
      transduction of immortalizing genes. The resulting cell lines had no major
      differences to their parental lines in their gene expression profiles. Similar to
      primary osteoblastic cells, osteocalcin transcription increased following 1,25
      dihydroxyvitamin D3 treatment and the immortalized cells formed a mineralized
      matrix, as detected by Alizarin Red staining. Moreover, these human cell lines
      responded by upregulating ALPL gene expression after treatment with the
      demethylating agent 5-aza-2'-deoxycytidine (AzadC), as shown before for primary
      osteoblasts. We further demonstrate that these cell lines can differentiate in
      vivo, using a hydroxyapatite/tricalcium phosphate composite as a scaffold, to
      produce bone matrix. More importantly, we show that these cells respond to
      demethylating treatment, as shown by the increase in SOST mRNA levels, the gene
      encoding sclerostin, upon treatment of the recipient mice with AzadC. This also
      confirms, in vivo, the role of DNA methylation in the regulation of SOST
      expression previously shown in vitro. Altogether our results show that these
      immortalized cell lines constitute a particularly useful model system to obtain
      further insight into bone homeostasis, and particularly into the epigenetic
      mechanisms regulating sclerostin production.

PMID- 27038991
TI  - Treatment of neovaginal prolapse: case report and systematic review of the
      literature.
AB  - INTRODUCTION AND HYPOTHESIS: Neovaginal prolapse (NP) is a rare event as few
      cases have been reported in the literature. Its management is complex and depends
      on the initial pathology, the vaginoplasty technique and the patient's history.
      We present a review the literature on this rare event. METHODS: We describe the
      case of a 72-year-old woman who presented with NP 1 year after pelvic
      exenteration and radiotherapy for recurrent cervical carcinoma associated with
      vaginal reconstruction by shaped-tube omentoplasty. She had undergone two
      previous surgical procedures (posterior sacrospinous ligament suspension and
      partial colpocleisis), but NP recurred each time within a few months. We
      performed an anterior approach to the sacrospinous ligament and inserted a mesh
      under the anterior wall of the neovagina, with the two mesh arms driven through
      the sacrospinous ligament in a tension-free manner (Uphold Lite(r) system). The
      MEDLINE, Cochrane Library, ClinicalTrials and OpenGrey databases were
      systematically searched for literature on the management of NP following bowel
      vaginoplasty, mechanical dilatation, graciloplasty, omentoplasty, rectus
      abdominis myocutaneous flap and the Davydov procedure. RESULTS: The postoperative
      course in the patient whose case is described was uneventful and after 1 year of
      follow-up, the anatomical results and patient satisfaction were good. The
      systematic search of the databases revealed several studies on the treatment of
      NP using abdominal and vaginal approaches, and these are reviewed. CONCLUSIONS:
      Overall, sacrocolpopexy would appear to be a good option for the treatment of
      prolapse after bowel vaginoplasty, but too few cases have been reported to
      establish this technique as the standard management of NP.

PMID- 27038992
TI  - Tissue reaction to urogynecologic meshes: effect of steroid soaking in two
      different mesh models.
AB  - INTRODUCTION AND HYPOTHESIS: Steroid soaking may decrease mesh-triggered
      inflammatory reaction in tissue. We aimed to investigate the tissue reaction to a
      steroid-soaked mesh material and an unsoaked mesh material in the rat model.
      METHODS: Neutral and steroid-soaked type I macroporous polypropylene (PP)
      monofilament and polyvinylidene fluoride (PVF) mesh materials were implanted on
      the rectus abdominis muscle of 20 mature Wistar albino rats. Animals were divided
      into four groups: PP mesh with steroid (PP-S), PP mesh without steroid, PVF mesh
      with steroid (PVF-S), and PVF mesh without steroid. The rats were killed after 12
      weeks, and histologic, immunohistochemical and electron microscopic examinations
      were performed. For immunohistochemical analysis, polyclonal rabbit anti-mouse
      CD3, rabbit anti-mouse CD68, rabbit anti-mouse CD15, and rabbit anti-mouse CD34
      antibodies were used for the detection of lymphocytes, macrophages,
      polymorphonuclear leukocyte foreign body giant cells, and fibromyocyte stem
      cells, respectively. Samples were stained with hematoxylin and eosin for the
      histologic evaluation of inflammation and with Masson's trichrome stain for the
      evaluation of collagen deposition. Pore size and mesh ultrastructure were
      evaluated by electron microscopy. RESULTS: Expression of CD3 was lower in the
      PVF, PVF-S and PP-S groups, and expression of CD34 was higher in the PVF-S and PP
      S groups than in the PP groups (p < 0.05). Collagen deposition was lower in the
      PVF, PVF-S and PP-S groups (p < 0.05). Histologically, the intensity of
      inflammation was lower in the PVF-S and PP-S groups than in the PP mesh group (p
      < 0.05). There were no significant differences among the groups in terms of pore
      size and mesh ultrastructure on electron microscopic examination (p > 0.05).
      CONCLUSIONS: PVF mesh induces less inflammation than PP mesh, and in both mesh
      types steroid soaking further decreases inflammation without changing the pore
      size.

PMID- 27038994
TI  - A rare coexistence of spinal subdural and subarachnoid hemorrhage as a
      consequence of anticoagulant administration.

PMID- 27038993
TI  - Plant species diversity affects soil-atmosphere fluxes of methane and nitrous
      oxide.
AB  - Plant diversity effects on ecosystem functioning can potentially interact with
      global climate by altering fluxes of the radiatively active trace gases nitrous
      oxide (N2O) and methane (CH4). We studied the effects of grassland species
      richness (1-16) in combination with application of fertilizer
      (nitrogen:phosphorus:potassium = 100:43.6:83 kg ha(-1) a(-1)) on N2O and CH4
      fluxes in a long-term field experiment. Soil N2O emissions, measured over 2 years
      using static chambers, decreased with species richness unless fertilizer was
      added. N2O emissions increased with fertilization and the fraction of legumes in
      plant communities. Soil CH4 uptake, a process driven by methanotrophic bacteria,
      decreased with plant species numbers, irrespective of fertilization. Using
      structural equation models, we related trace gas fluxes to soil moisture, soil
      inorganic N concentrations, nitrifying and denitrifying enzyme activity, and the
      abundance of ammonia oxidizers, nitrite oxidizers, and denitrifiers (quantified
      by real-time PCR of gene fragments amplified from microbial DNA in soil). These
      analyses indicated that plant species richness increased soil moisture, which in
      turn increased N cycling-related activities. Enhanced N cycling increased N2O
      emission and soil CH4 uptake, with the latter possibly caused by removal of
      inhibitory ammonium by nitrification. The moisture-related indirect effects were
      surpassed by direct, moisture-independent effects opposite in direction.
      Microbial gene abundances responded positively to fertilizer but not to plant
      species richness. The response patterns we found were statistically robust and
      highlight the potential of plant biodiversity to interact with climatic change
      through mechanisms unrelated to carbon storage and associated carbon dioxide
      removal.

PMID- 27038995
TI  - Resection of liver metastases in patients with gastrointestinal stromal tumors in
      the imatinib era: A nationwide retrospective study.
AB  - INTRODUCTION: Liver metastases are common in patients with gastrointestinal
      stromal tumors (GIST). In the absence of randomized controlled clinical trials,
      the effectiveness of surgery as a treatment modality is unclear. This study
      identifies safety and outcome in a nationwide study of all patients who underwent
      resection of liver metastases from GIST. METHODS: Patients were included using
      the national registry of histo- and cytopathology (PALGA) of the Netherlands from
      1999. Kaplan Meier survival analysis was used for calculating survival outcome.
      Univariate and multivariate regression analyses were carried out for the
      assessment of potential prognostic factors. RESULTS: A total of 48 patients (29
      male, 19 female) with a median age of 58 (range 28-81) years were identified.
      Preoperative and postoperative tyrosine kinase inhibitor therapy was given to 30
      (63%) and 36 (75%) patients, respectively. A minor liver resection was performed
      in 32 patients, 16 patients underwent major liver resection. Median follow-up was
      27 (range 1-146) months. Median progression-free survival (PFS) was 28 (range 1
      121) months. One-, three-, and five-year PFS was 93%, 67%, and 59% respectively.
      Median overall survival (OS) was 90 (range 1-146) months from surgery. The one-,
      three-, and five-year OS was 93%, 80%, and 76% respectively. R0 resection was the
      only independent significant prognostic factor for DFS and OS at multivariate
      analysis. CONCLUSION: Resection of liver metastases in GIST patients combined
      with imatinib may be associated with prolonged overall survival when a complete
      resection is achieved.

PMID- 27038996
TI  - The circumferential resection margins status: A comparison of robotic,
      laparoscopic and open total mesorectal excision for mid and low rectal cancer.
AB  - INTRODUCTION: Minimally invasive surgery for rectal cancer (RC) is now widely
      performed via the laparoscopic approach, but robotic-assisted surgery may
      overcome some limitations of laparoscopy in RC treatment. We compared the rate of
      positive circumferential margins between robotic, laparoscopic and open total
      mesorectal excision (TME) for RC in our institution. METHODS: Mid and low rectal
      adenocarcinoma patients consecutively submitted to robotic surgery were compared
      to laparoscopic and open approach. From our prospective database, 59 patients
      underwent robotic-assisted rectal surgery from 2012 to 2015 (RTME group) were
      compared to our historical control group comprising 200 open TME (OTME group) and
      41 laparoscopic TME (LTME group) approaches from July 2008 to February 2012.
      Primary endpoint was to compare the rate of involved circumferential resection
      margins (CRM) and the mean CRM between the three groups. Secondary endpoint was
      to compare the mean number of resected lymph nodes between the three groups.
      RESULTS: CRM involvement was demonstrated in 20 patients (15.5%) in OTME, 4 (16%)
      in LTME and 9 (16.4%) in the RTME (p = 0.988). The mean CRM in OTME, LTME and
      RTME were respectively 0.6 cm (0-2.7), 0.7 cm (0-2.0) and 0.6 cm (0-2.0) (p =
      0.960). Overall mean LN harvest was 14 (0-56); 16 (0-52) in OTME, 13 (1-56) in
      LTME and 10 (0-45) in RTME (p = 0.156). CONCLUSION: Our results suggest that
      robotic TME has the same oncological short-term results when compared to the open
      and laparoscopic technique, and it could be safely offered for the treatment of
      mid and low rectal cancer.

PMID- 27038997
TI  - Cost versus control: Understanding ownership through outsourcing in hospitals.
AB  - For-profit hospitals in California contract out services much more intensely than
      either private nonprofit or public hospitals. To explain why, we build a model in
      which the outsourcing decision is a trade-off between cost and control. Since
      nonprofit firms are more restricted in how they consume net revenues, they
      experience more rapidly diminishing value of a dollar saved, and they are less
      attracted to a low-cost but low-control outsourcing opportunity than a for-profit
      firm is. This difference is exaggerated in services where the benefits of
      controlling the details of production are particularly important but minimized
      when a fixed-cost shock raises the marginal value of a dollar of cost savings. We
      test these predictions in a panel of California hospitals, finding evidence for
      each and that the set of services that private non-profits are particularly
      interested in controlling (physician-intensive services) is very different from
      those than public hospitals are particularly interested in (labor-intensive
      services). These results suggest that a model of public or nonprofit make-or-buy
      decisions should be more than a simple relabeling of a model derived in the for
      profit context.

PMID- 27038999
TI  - Six Years and a Column: The Evolution of a Specialty.

PMID- 27038998
TI  - Augmented Image Interpretation Through the Use of Advanced Health Record
      Technology.

PMID- 27039000
TI  - Managing Scale and Innovation in Health IT.
AB  - Given the high-intensity interaction between radiology and IT, radiology
      leadership should understand IT's new, somewhat conflicting, dual roles. Managing
      large-scale and small-scale projects concurrently has become an important
      challenge for leaders of health IT (HIT). Historical parallels of this challenge
      can be drawn from transportation and communication systems, in which a large
      scale mind-set is needed to build the initial network, whereas a small-scale mind
      set is more useful to develop the content that will traverse this network.
      Innovation and creativity is a cornerstone of content small-scale thinking, and
      in HIT, that is what is needed to extract the value from it. However, unlike the
      early historical transportation and communication examples, the time between the
      development of the infrastructure and the follow-on, value-rich content is
      shortened greatly because it has become nearly simultaneous in HIT. Weaving the
      ability to concomitantly manage both large- and small-scale projects into the
      fabric of the organizational HIT culture will be critical for its success. 

PMID- 27039001
TI  - Panacea or Sham? Legal Issues of Vertebroplasty.

PMID- 27039002
TI  - Detection of Cardiac Incidental Findings on Routine Chest CT: The Impact of
      Dedicated Training in Cardiac Imaging.
AB  - PURPOSE: Routine chest CT and cardiac CT angiography (CTA) both image the heart,
      albeit with different precision and intent. The aim of this study was to evaluate
      the diagnostic ability of radiologists with different levels of cardiac training
      to identify cardiac findings on chest CT without electrocardiographic gating
      compared with a reference standard of electrocardiographically gated cardiac CTA.
      METHODS: Electrocardiographically gated cardiac CT angiographic studies performed
      between January 2005 to January 2010 in patients with routine chest CT within six
      months were retrospectively identified. Fourteen radiologists at four stages of
      training (stage 1, residents with no cardiac training [n = 4]; stage 2, residents
      who had completed at least one dedicated rotation of cardiac imaging [n = 3];
      stage 3, radiologists without cardiac training [n = 3]; and stage 4, radiologists
      with formal cardiac fellowship training [n = 4]) performed blinded, anonymized
      cardiac readings of chest CT images. Findings were categorized (coronary
      arterial, noncoronary vessel, cardiac chamber, myocardial, pericardial, and valve
      findings) with cardiac CTA as a reference standard. RESULTS: Overall, 140 cardiac
      CT angiographic findings were reported in 63 of 77 patients. The sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of nongated CTA were 43.6%, 96.8%, 83.0%, 81.6%, and 81.8%, respectively, for all
      readers. Increasing training was associated with higher sensitivity (30.3%,
      35.7%, 45.7%, and 61.2% from stages 1 to 4) but similar specificity (96.4%,
      96.7%, 96.3%, and 97.6% from stages 1 to 4). Frequently missed findings
      categories were coronary arterial, myocardial, and cardiac chamber findings.
      CONCLUSIONS: Increasing cardiac imaging training correlates with increased
      sensitivity and stable specificity to detect cardiac findings on routine chest CT
      without electrocardiographic gating. Cardiac findings should be noted on chest CT
      when observed, and cardiac training should be encouraged.

PMID- 27039003
TI  - Osteoradionecrosis following treatment for head and neck cancer and the effect of
      radiotherapy dosimetry: the Guy's and St Thomas' Head and Neck Cancer Unit
      experience.
AB  - OBJECTIVES: To analyze clinical features, dosimetric parameters, and outcomes of
      osteoradionecrosis (ORN). STUDY DESIGN: Thirty-six patients with ORN who had been
      previously treated with radiotherapy (RT) were retrospectively identified between
      January 2009 and April 2014. ORN volumes were contoured on planning computed
      tomography (CT) scans. Near maximum dose (D2%), minimum dose (Dmin), mean dose
      (Dmean), and percentage of bone volume receiving 50 Gy (V50) were examined.
      Clinical and dosimetric variables were considered to compare ORN resolution
      versus ORN persistence. RESULTS: Median interval time from end of RT to
      development of ORN was 6 months. Of the ORN cases, 61% were located in the
      mandible. Dmean to affected bone was 57.6 Gy, and 44% had a D2% 65 Gy or greater.
      Smoking was associated with ORN persistence on univariate analysis, but no
      factors were found to impact ORN resolution or progression on logistic
      regression. CONCLUSIONS: Prevention strategies for ORN development should be
      prioritized. Dose-volume parameters could have a role in preventing ORN.

PMID- 27039004
TI  - Assault-related facial injuries during the season of goodwill.
AB  - OBJECTIVE: The aim of this study was to assess if the "season of goodwill," over
      the 12 days of Christmas, manifests in a reduction in the rate of maxillofacial
      injuries secondary to interpersonal violence. STUDY DESIGN: We performed a
      retrospective analysis at a teaching hospital in the United Kingdom. We
      identified consecutive patients presenting at our institution with facial
      injuries secondary to assault during the Christmas season, together with
      corresponding Easter time and control periods. Data for 4 consecutive years
      starting from 2010 were collected. We compared the rates of presentation of
      facial injuries over the Christmas season with those occurring during Easter and
      control periods. Our outcome measures included frequency distributions of facial
      injuries secondary to assault as well as maxillofacial injury patterns. RESULTS:
      For the study, 440 patients met the inclusion criteria, with 194 presentations
      occurring during the Christmas season, 132 presentations over Easter, and 114
      over the control period (P = .006). There was a statistically significant
      difference in the mean rates of presentation between the Christmas and Easter
      seasons (P = .03) and also between the Christmas and control periods (P = .02).
      We noted an increasing annual trend during the study period in the frequency of
      assault-related facial injuries during Christmas. CONCLUSIONS: Our data suggest
      that the rate of assault-related facial trauma during Christmas is significantly
      greater compared with that for both the Easter holiday period and the baseline
      presentation rate. The "season of goodwill," therefore, does not appear to
      manifest in a reduction in the rate of assault-related facial injuries. This
      increased trauma workload requires strategic planning to ensure adequate clinical
      cover for these anticipated busy periods.

PMID- 27039005
TI  - Primary mucosal melanoma of the oral cavity: current therapy and future
      directions.
AB  - BACKGROUND: Primary mucosal melanoma of the oral cavity is a highly aggressive
      malignancy of melanocytic origin. The aim of this study is to report a case
      series of oral mucosal melanomas (OMMs) and provide a review of the literature
      with regard to treatment guidelines for and prognosis of this pathologic entity.
      STUDY DESIGN: We report three cases of OMMs treated in our institutions and the
      results of a literature review, in which the words "oral" and "mucosal melanoma"
      were used as the main keywords. RESULTS: Surgical resection of the primary tumor
      with wide resection margins appears to be the recommended primary treatment
      modality with the aim to achieve tumor-free margins. Elective neck dissection and
      adjuvant radiotherapy have been advocated for locoregional control. Chemotherapy
      has not been shown to improve survival and is mainly used for palliative
      purposes. Immunotherapy and biochemotherapy seem to significantly improve
      survival and could open new therapeutic horizons. CONCLUSIONS: The prognosis of
      OMMs remains poor despite treatment. Early diagnosis and aggressive surgical
      resection followed by adjuvant therapies could be the key to improving survival.
      Multicenter randomized clinical trials, which may be difficult to conduct because
      of the rarity to the lesion, would aid in the development of new strategies.

PMID- 27039007
TI  - Assessment of furcal perforations in the vicinity of different root canal sealers
      using a cone beam computed tomography system with and without the application of
      artifact reduction mode: an ex vivo investigation on extracted human teeth.
AB  - OBJECTIVE: To investigate observer ability to diagnose ex vivo simulated
      endodontic furcal perforations in root-filled teeth from cone beam computed
      tomography (CBCT) images using different artifact reduction algorithms. STUDY
      DESIGN: Our study consisted of 135 first maxillary molar teeth. In 89 teeth,
      furcation perforations were created using dental burs. Forty-six teeth without
      artificial perforations were used as controls. MTA Fillapex, Activ GP, and AH
      Plus were used with or without metal posts. All teeth were imaged using Planmeca
      ProMax 3-D Max CBCT, and four image modes were obtained as without artifact
      reduction and with artifact reduction in low, medium, and high modes. Images were
      evaluated by three observers for the presence or absence of furcation perforation
      using a five-point scale. Weighted kappa coefficients were calculated to assess
      observer agreement. Receiver operating characteristic analysis was performed.
      Areas under the curve (AUCs) were calculated for each image mode, observer,
      treatment group, and reading and were compared using Chi(2) tests, with a
      significance level of alpha = 0.05. The effects on diagnosis were calculated
      using analysis of variance (ANOVA). RESULTS: Intraobserver agreements for all
      observers ranged from 0.857 to 0.945. Kappa coefficients among different
      observers ranged from 0.673 to 0.763. AUC values ranged from 0.83 to 0.92, and
      there were no statistically significant differences (P > .05) between different
      CBCT image modes. Ratings in Activ GP treatment groups with or without posts
      showed statistically significant differences (P < .001). CONCLUSIONS: All CBCT
      image modes performed similarly in detecting furcal perforations near different
      root canal sealers with or without posts.

PMID- 27039006
TI  - Inherent physical characteristics and gene expression differences between
      alveolar and basal bones.
AB  - OBJECTIVES: The objective of this study was to evaluate the baseline differences
      between alveolar and basal areas of the rat mandible. STUDY DESIGN: Rat
      mandibular alveolar and basal bones were evaluated using histology and micro
      computed tomography to compare osteocyte number as well as bone density and
      architecture and polymerase chain reaction to measure gene expression levels.
      RESULTS: Micro-computed tomography data indicated that basal bone is denser and
      less porous than alveolar bone. Histologic analysis showed that alveolar bone has
      more osteocytes per unit area compared with basal bone. Real-time polymerase
      chain reaction results showed higher levels of expression of the following genes
      in basal bone than in alveolar bone: SOST, E-11, DMP-1, and MEPE. CONCLUSIONS:
      Three of these gene products are associated with mature osteocytes, and this
      suggests that basal bone has more mature osteocyte phenotypes compared with
      alveolar bone. These findings are suggestive of fewer bone mineralization units
      and therefore a slower remodeling rate.

PMID- 27039008
TI  - Pattern of recurrence of nonsyndromic keratocystic odontogenic tumors.
AB  - OBJECTIVE: To describe and analyze recurrent pattern of KOTs according to time.
      STUDY DESIGN: This retrospective chart study evaluated histologically confirmed
      nonsyndromic keratocystic odontogenic tumors (KOT) treated at our institutions
      between 1975 and 2012. RESULTS: Mean age at time of diagnosis was 48 years, and
      male/female ratio was 1.8:1. The typical nonsyndromic KOT lesion was most often
      found in the posterior mandible, had radiographically smooth borders, and was
      associated with symptoms and clinical findings, perforated bone, with a thin
      capsule. Anterior jaw KOT were found more frequently in patients 50 years or
      older, and maxillary KOTs were more frequently infected. Treatment was
      enucleation (n = 70) or marsupialization with subsequent enucleation (n = 22).
      Observation time ranged from 0.5 months to 25 years (mean 53 months). Crude
      recurrence rate was 29%. Risk of recurrence increased until 7 years after
      treatment and then remained stable. Patients with impaired general health had a
      significantly increased risk of recurrence. Tumors in the posterior mandible that
      had bone perforation and a thin capsule and contained keratin showed increased
      recurrence rates. Although recurrence rates were similar for both treatment
      groups, the groups differed in size and tumor site; thus, the results of this
      study need to be confirmed in a prospective study. CONCLUSIONS: Time-dependent
      recurrence pattern of KOTs is described and analyzed. The following follow-up
      protocol is suggested for patients with impaired health or large lesions:
      clinical and radiographic examinations at 2, 4, and 7 years, followed by
      intervals of 3 to 4 years; for other patients: clinical and radiographic
      examination at 4, 6, and 8 years, followed by intervals of 3 to 4 years.

PMID- 27039009
TI  - Associations of acoustically measured tongue/jaw movements and portion of time
      speaking with negative symptom severity in patients with schizophrenia in Italy
      and the United States.
AB  - This is the first cross-language study of the effect of schizophrenia on speech
      as measured by analyzing phonetic parameters with sound spectrography. We
      hypothesized that reduced variability in pitch and formants would be correlated
      with negative symptom severity in two samples of patients with schizophrenia, one
      from Italy, and one from the United States. Audio recordings of spontaneous
      speech were available from 40 patients. From each speech sample, a file of F0
      (pitch) and formant values (F1 and F2, resonance bands indicating the moment-by
      moment shape of the oral cavity), and the portion of the recording in which there
      was speaking ("fraction voiced," FV), was created. Correlations between
      variability in the phonetic indices and negative symptom severity were tested and
      further examined using regression analyses. Meaningful negative correlations
      between Scale for the Assessment of Negative Symptoms (SANS) total score and
      standard deviation (SD) of F2, as well as variability in pitch (SD F0) were
      observed in the Italian sample. We also found meaningful associations of SANS
      affective flattening and SANS alogia with SD F0, and of SANS avolition/apathy and
      SD F2 in the Italian sample. In both samples, FV was meaningfully correlated with
      SANS total score, avolition/apathy, and anhedonia/asociality.

PMID- 27039010
TI  - The reliability and validity of the Maryland Assessment of Recovery in Serious
      Mental Illness Scale.
AB  - The current study aims to further evaluate the psychometric properties of the
      Maryland Assessment of Recovery in Serious Mental Illness (MARS), a relatively
      new instrument designed to assess personal recovery status in individuals with
      serious mental illness. Two hundred and fifty individuals with serious mental
      illness receiving outpatient mental health treatment completed a baseline
      assessment which included the MARS and measures to assess recovery-related
      constructs, clinical outcomes, and social and community functioning. The MARS
      demonstrated excellent internal consistency and test-retest reliability. Good
      construct validity was evidenced by strong positive relationships between the
      MARS and recovery-related constructs (e.g. hope, empowerment, self-efficacy, and
      personal agency) and a strong negative relationship with self-stigma. Divergent
      validity was demonstrated by weaker relationships with cognitive and social
      functioning. The confirmatory factor analysis did not confirm the unitary factor
      structure found in previous research. Given the equivocal result of the CFA,
      additional exploratory work is needed to determine if a more complex factor
      structure is present. This study provides addition support for the psychometric
      soundness of the MARS and subsequently, its potential use as a measure of
      personal recovery status in people with serious mental illness.

PMID- 27039011
TI  - Cross-cultural confirmation of bi-factor models of a symptom distress measure:
      Symptom Checklist-90-Revised in clinical samples.
AB  - Four decades have elapsed since the introduction for clinical and research
      purposes of the Symptom Checklist-90(-R). Yet, its underlying dimensional
      structure has not been clearly delineated. A shift has been observed in the
      methods utilized-from predominantly exploratory factor analytic in nature in the
      first two decades or so to different confirmatory methods in recent years. A need
      remains to search for a structure that remains invariant across samples and
      nations. In that context, the present study attempted to replicate and extend
      recent findings yielded in a Hungarian general population sample (N=2,874) with
      two psychiatric patient samples from Hungary (N=972) and The Netherlands
      (N=1,902). In doing so, four models were contrasted: the one-factor model,
      Derogatis' nine factor model, a second-ordered factor model, and a bi-factor
      model. The bi-factor model was shown to yield the closest fit to the data in both
      countries. Further studies are needed to determine the stable number and kind of
      subscale scores that reflect the specific (primary) symptoms best, that is, those
      subscales with minimal shared variance with the overall general psychological
      distress dimension.

PMID- 27039012
TI  - The manic phase of Bipolar disorder significantly impairs theory of mind
      decoding.
AB  - Bipolar disorder is associated with significant deficits in the decoding of
      others' mental states in comparison to healthy participants. However, differences
      in theory of mind decoding ability among patients in manic, depressed, and
      euthymic phases of bipolar disorder is currently unknown. Fifty-nine patients
      with bipolar I or II disorder (13 manic, 25 depressed, 20 euthymic) completed the
      "Reading the Mind in the Eyes" Task (Eyes task) and the Animals Task developed to
      control for non-mentalistic response demands of the Eyes Task. Patients also
      completed self-report and clinician-rated measures of depression, mania, and
      anxiety symptoms. Patients in the manic phase were significantly less accurate
      than those in the depressed and euthymic phases at decoding mental states in the
      Eyes task, and this effect was strongest for eyes of a positive or neutral
      valence. Further Eyes task performance was negatively correlated with the
      symptoms of language/thought disorder, pressured speech, and disorganized
      thoughts and appearance. These effects held when controlling for accuracy on the
      Animals task, response times, and relevant demographic and clinical covariates.
      Results suggest that the state of mania, and particularly psychotic symptoms that
      may overlap with the schizophrenia spectrum, are most strongly related to social
      cognitive deficits in bipolar disorder.

PMID- 27039013
TI  - U.S. Physicians' Opinions About Accommodating Religiously Based Requests for
      Continued Life-Sustaining Treatment.
AB  - CONTEXT: Families of critically ill patients occasionally request that physicians
      continue life-sustaining treatment (LST), sometimes giving religious reasons.
      OBJECTIVES: To examine whether U.S. physicians are more likely to accommodate
      requests for LST that are based on religious reasons. METHODS: In 2010, we
      surveyed 1156 practicing U.S. physicians from specialties likely to care for
      adult patients with advanced illness. The questionnaire included two randomized
      experimental vignettes: one where a family asked that LST be continued for a
      patient that met brain death criteria and a second where the son of an elderly
      patient with cancer insists on continuing LST. In both, we experimentally varied
      the reasons that the family member gave to justify the request, to see if
      physicians are more likely to accommodate a request based on a religious
      requirement or hope for a miracle, compared to no mention of either. For
      physicians' religious characteristics, we assessed their religious affiliation
      and level of religiosity. RESULTS: For the patient meeting brain death criteria,
      physicians were more likely to accommodate the request to continue LST when the
      family mentioned their Orthodox Jewish community (85% vs. 70%, P < 0.001). For
      the patient with metastatic cancer, physicians were more likely to accommodate
      the request when the son said his religious faith does not permit discontinuing
      LST (65% vs. 46%, P < 0.001), but not when he said he expected divine healing
      (50% vs. 46%). CONCLUSION: Physicians appear more willing to accommodate requests
      to continue LST when those requests are based on particular religious communities
      or traditions, but not when based on expectations of divine healing.

PMID- 27039014
TI  - Frailty measurement in research and clinical practice: A review.
AB  - One of the leading causes of morbidity and premature mortality in older people is
      frailty. Frailty occurs when multiple physiological systems decline, to the
      extent that an individual's cellular repair mechanisms cannot maintain system
      homeostasis. This review gives an overview of the definitions and measurement of
      frailty in research and clinical practice, including: Fried's frailty phenotype;
      Rockwood and Mitnitski's Frailty Index (FI); the Study of Osteoporotic Fractures
      (SOF) Index; Edmonton Frailty Scale (EFS); the Fatigue, Resistance, Ambulation,
      Illness and Loss of weight (FRAIL) Index; Clinical Frailty Scale (CFS); the
      Multidimensional Prognostic Index (MPI); Tilburg Frailty Indicator (TFI); PRISMA
      7; Groningen Frailty Indicator (GFI), Sherbrooke Postal Questionnaire (SPQ); the
      Gerontopole Frailty Screening Tool (GFST) and the Kihon Checklist (KCL), among
      others. We summarise the main strengths and limitations of existing frailty
      measurements, and examine how well these measurements operationalise frailty
      according to Clegg's guidelines for frailty classification - that is: their
      accuracy in identifying frailty; their basis on biological causative theory; and
      their ability to reliably predict patient outcomes and response to potential
      therapies. 

PMID- 27039015
TI  - Barriers and facilitators to reaching a diagnosis of PNES from the patients'
      perspective: Preliminary findings.
AB  - PURPOSE: This qualitative study aimed at examining the subjective experiences of
      patients during the complicated and often prolonged diagnostic process of
      psychogenic non-epileptic seizures (PNES). METHODS: Thematic analyses were used
      to explore the semi-structured interviews that were conducted with ten
      individuals who have been diagnosed with PNES. RESULTS: Six main themes, namely
      inexpert healthcare providers, limited medical insurance and loss of independence
      were identified as barriers, while social support, comprehensive medical
      insurance and knowledgeable healthcare providers were identified as facilitators
      through the process of thematic analysis. CONCLUSIONS: The patients' perspectives
      revealed that an earlier diagnosis of PNES is essential to address the loss of
      independence and limit inappropriate and potentially harmful treatment as well as
      the costly burden of this condition on both the patient and the healthcare
      system. It was evident in this study that healthcare providers play an essential
      role in the subjective experiences of these individuals during the diagnostic
      process. The implementation of continuous education programmes for healthcare
      providers in particular could contribute positively to the diagnostic process of
      PNES for patients.

PMID- 27039016
TI  - Assessing the value of topiramate in refractory status epilepticus.
AB  - PURPOSE: The aim of this study was to assess factors associated with the use of
      topiramate (TPM) in refractory status epilepticus (RSE). METHODS: We
      retrospectively reviewed RSE episodes over a 12-year period. Episodes treated
      with and without TPM were compared in terms of demographics, RSE characteristics,
      clinical course, and outcome in univariate and multivariate analyses. Subgroups
      defined by type of RSE were studied separately. Functional outcome was assessed
      with the modified Rankin Scale. RESULTS: Among 71 episodes, 17 (23.9%) were
      treated with TPM and seizure control was achieved in all of these. The results of
      unadjusted comparisons suggested a use of TPM in younger and healthier patients
      who received more perseverant treatment indicated by a higher number of
      antiepileptic drugs applied. In multivariate analysis adjusting for RSE duration,
      however, these associations lost significance. Furthermore, TPM was not a
      predictor of successful RSE termination in neither the overall cohort, nor in the
      subgroup of complex-partial RSE. CONCLUSION: After multivariate adjustment, no
      significant differences were observed between episodes treated with and without
      TPM in baseline characteristics, treatment, and outcome. Regarding the latter,
      this study does therefore not yield evidence for a particular efficacy of TPM in
      RSE.

PMID- 27039017
TI  - Long-term exposure to political violence: The particular injury of persistent
      humiliation.
AB  - This study assessed the association between exposure to political violence over a
      25-year period and adult functioning among a population that has experienced
      protracted and severe political conflict. Instead of aggregating exposure to
      political violence across time and type of exposure, as is commonly done, the
      event history calendar pioneered in this study assessed exposure to five forms of
      political violence annually from 1987 to 2011 in a representative sample of 1788
      adults, aged 37 on average, in the occupied Palestinian territories (West Bank,
      East Jerusalem, and the Gaza Strip). This method allowed for the identification
      of trajectories of exposure to political violence from childhood to adulthood
      using latent profile analysis. We then correlated the trajectories of exposure to
      measures of economic, political, community, family, psychological, and health
      functioning. As expected, being shot at, having one's home raided, being hit or
      kicked, being verbally abused, and witnessing someone close being humiliated were
      all elevated during periods of heightened political conflict (the first intifada
      (1987-1993) and, less so, the second intifada (2000-2005)). In addition, 12% of
      women and men reported high and persistent levels of exposure to humiliation
      (being verbally abused and/or witnessing someone close being humiliated) across
      the entire 25-year period. These individuals lived predominantly in neighborhoods
      with a high Israeli military presence. Compared to those who experienced periodic
      exposure to political violence, persistently humiliated men and women reported
      significantly lower health, economic, political, and psychological functioning,
      as well as higher social cohesion and political expression. Relevant literatures
      are reviewed when concluding that persistent humiliation is a neglected form of
      political violence that is best represented as a direct (versus structural),
      acute (versus chronic), macro (versus micro), and high-grade (versus low-grade)
      stressor whose particular injury is due to the violation of individual and
      collective identity, rights, justice and dignity. 

PMID- 27039018
TI  - About one-half of adults with active epilepsy and seizures have annual family
      incomes under $25,000: The 2010 and 2013 US National Health Interview Surveys.
AB  - People with active epilepsy are those who reported being told that they have
      epilepsy or a seizure disorder and either take antiseizure medication or have had
      a seizure during the past 12months. We used combined 2010 and 2013 National
      Health Interview Survey (NHIS) data on US adults with active epilepsy to examine
      whether taking medications and seizure frequency differed by sex, age,
      race/ethnicity, and reported or imputed annual family income. Of adults with
      active epilepsy, 45.5% reported taking medication and having at least one
      seizure, 41.3% reported taking medication and having no seizures, and 13.2%
      reported not taking any medication and having at least one seizure. About one
      half of adults with active epilepsy and seizures have annual family incomes of
      less than $25,000. Promoting self-management supports and improved access to
      specialty care may reduce the burden of uncontrolled seizures in adults with
      epilepsy.

PMID- 27039019
TI  - Spatio-temporal coordination of cell cycle exit, fusion and differentiation of
      adult muscle precursors by Drosophila Erect wing (Ewg).
AB  - The mechanisms of cell cycle exit by myoblasts during skeletal muscle development
      are poorly understood. Cell cycle arrest is known to be a prerequisite for
      myoblast fusion and subsequent differentiation. Despite tremendous knowledge on
      myoblast fusion and differentiation, tissue-specific factors that spatio
      temporally regulate the cell cycle exit are not well known. In this paper, we
      show that the transcriptional factor/co-activator "Erect wing" (Ewg) synchronises
      myoblast cell cycle exit with that of the fusion process. Ewg-null myoblasts show
      delayed temporal development of dorsal longitudinal muscles (DLMs), a group of
      indirect flight muscles (IFMs), which culminates to abnormal and asymmetric
      muscle pattern. A role for Ewg in cell cycle exit at G1/S stage is also shown.
      Reducing Cyclin E dose in Ewg-null mutant rescues the lack of IFMs and flight
      ability. Thus, we show that Ewg repression of Cyclin E expression is required for
      the arrest of myoblast proliferation and initiate myoblast fusion and terminal
      differentiation.

PMID- 27039021
TI  - Correlation of Histologic Features with In Vivo Imaging of Reticular
      Pseudodrusen.
AB  - PURPOSE: To determine the histologic and cellular correlates in the retina and
      retinal pigment epithelium (RPE) with the presence of optical coherence
      tomography-defined reticular pseudodrusen (RPD). DESIGN: Observation case using
      immunocytochemistry of an exenterated eye with immediate fixation after removal.
      PARTICIPANTS: Two patients, one with confirmed RPD and the other with mid
      peripheral drusen, underwent multimethod imaging before exenteration and
      immediate fixation of the posterior eyecup for high-resolution immunocytochemical
      analysis. METHODS: Optical coherence tomography (OCT) was compared with high
      resolution immunocytochemistry using a range of cellular markers to determine
      changes in the RPE, photoreceptors, and gliosis. MAIN OUTCOME MEASURES:
      Correlations of the appearance of reticular pseudodrusen on OCT and
      immunocytochemical analysis. RESULTS: Reticular pseudodrusen were deposits
      juxtaposed to photoreceptor outer segments extending through the outer nuclear
      layer and even beyond the outer limiting membrane. Deposits were rich in
      vitronectin, photoreceptor-associated proteins, and Iba1-immunoreactive immune
      cells. In contrast to conventional drusen the lipid stain Oil Red O failed to
      stain RPD. Cellular analysis revealed that RPD were associated with photoreceptor
      disruption and loss and localized gliosis. In addition, anomalies in the RPE were
      observed. CONCLUSIONS: Reticular pseudodrusen represent subretinal deposits that
      extend through the outer nuclear layer, affect photoreceptor integrity, and are
      associated with retinal gliosis and RPE damage.

PMID- 27039020
TI  - Molecular Architecture of the Retroviral Capsid.
AB  - Retroviral capsid cores are proteinaceous containers that self-assemble to encase
      the viral genome and a handful of proteins that promote infection. Their function
      is to protect and aid in the delivery of viral genes to the nucleus of the host,
      and, in many cases, infection pathways are influenced by capsid-cellular
      interactions. From a mathematical perspective, capsid cores are polyhedral cages
      and, as such, follow well-defined geometric rules. However, marked morphological
      differences in shapes exist, depending on virus type. Given the specific roles of
      capsid in the viral life cycle, the availability of detailed molecular
      structures, particularly at assembly interfaces, opens novel avenues for targeted
      drug development against these pathogens. Here, we summarize recent advances in
      the structure and understanding of retroviral capsid, with particular emphasis on
      assemblies and the capsid cores.

PMID- 27039022
TI  - Individualized Stabilization Criteria-Driven Ranibizumab versus Laser in Branch
      Retinal Vein Occlusion: Six-Month Results of BRIGHTER.
AB  - PURPOSE: To compare the 6-month efficacy and safety profile of an individualized
      stabilization criteria-driven pro re nata (PRN) regimen of ranibizumab 0.5 mg
      with or without laser versus laser alone in patients with visual impairment due
      to macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN: A 24
      month, prospective, open-label, randomized, active-controlled, multicenter, phase
      IIIb study. PARTICIPANTS: A total of 455 patients. METHODS: Eligible patients
      were randomized 2:2:1 to receive ranibizumab (n = 183), ranibizumab with laser (n
      = 180), or laser only (n = 92). Patients treated with ranibizumab with or without
      laser received a minimum of 3 initial monthly ranibizumab injections until visual
      acuity (VA) stabilization, and VA-based PRN dosing thereafter. In the ranibizumab
      with laser and laser-only groups, laser was given at the investigator's
      discretion at a minimum interval of 4 months and if VA was <79 letters. MAIN
      OUTCOME MEASURES: Mean change from baseline at month 6 in best-corrected visual
      acuity (BCVA) (primary end point) and central subfield thickness, and safety over
      6 months. Exploratory objectives were to evaluate the influence of baseline BCVA,
      disease duration, and ischemia on BCVA outcomes at month 6. RESULTS: Baseline
      mean BCVA was 57.7 letters, and mean BRVO duration was 9.9 months. Ranibizumab
      with or without laser was superior to laser only in improving mean BCVA from
      baseline at month 6 (14.8 and 14.8 vs. 6.0 letters; both P < 0.0001; primary end
      point met). Patients with a shorter BRVO duration at baseline had a higher mean
      BCVA gain than those with a longer BRVO duration. Patients with a poor baseline
      VA had a better BCVA gain than those with a higher baseline VA, although final
      BCVA was lower in those with poor baseline VA. In the ranibizumab with or without
      laser groups, the presence of some macular ischemia at baseline did not influence
      mean BCVA gains. There were no new ocular or nonocular safety events.
      CONCLUSIONS: Ranibizumab with an individualized VA-based regimen, with or without
      laser, showed statistically significant superior improvement in BCVA compared
      with laser alone in patients with BRVO. Overall, there were no new safety events
      other than those reported in previous studies.

PMID- 27039023
TI  - Branching of keratin intermediate filaments.
AB  - Keratin intermediate filaments (IFs) are crucial to maintain mechanical stability
      in epithelial cells. Since little is known about the network architecture that
      provides this stiffness and especially about branching properties of filaments,
      we addressed this question with different electron microscopic (EM) methods.
      Using EM tomography of high pressure frozen keratinocytes, we investigated the
      course of several filaments in a branching of a filament bundle. Moreover we
      found several putative bifurcations in individual filaments. To verify our
      observation we also visualized the keratin network in detergent extracted
      keratinocytes with scanning EM. Here bifurcations of individual filaments could
      unambiguously be identified additionally to bundle branchings. Interestingly,
      identical filament bifurcations were also found in purified keratin 8/18
      filaments expressed in Escherichia coli which were reassembled in vitro. This
      excludes that an accessory protein contributes to the branch formation.
      Measurements of the filament cross sectional areas showed various ratios between
      the three bifurcation arms. This demonstrates that intermediate filament
      furcation is very different from actin furcation where an entire new filament is
      attached to an existing filament. Instead, the architecture of intermediate
      filament bifurcations is less predetermined and hence consistent with the general
      concept of IF formation.

PMID- 27039024
TI  - Role of human GRP75 in miRNA mediated regulation of dengue virus replication.
AB  - In recent times, RNAi has emerged as an important defence system that regulates
      replication of pathogens in host cells. Many RNAi related host factors especially
      the host miRNAs play important roles in all intrinsic cellular functions,
      including viral infection. We have been working on identification of mammalian
      host factors involved in Dengue virus infection. In the present study, we
      identified Glucose Regulated Protein 75kDa (GRP75), as a host factor that is
      associated with dicer complex, in particular with HADHA (trifunctional enzyme
      subunit alpha, mitochondrial), an auxiliary component of dicer complex. Knockdown
      of GRP75 by respective siRNAs in Huh-7 cells resulted in the accumulation of
      dengue viral genomic RNA suggesting a role of GRP75 in regulating dengue virus
      replication in human cell lines. To elucidate the mode of action of GRP75, we
      over expressed the protein in Huh-7 cells and analysed the host miRNAs
      processing. The results revealed that, GRP75 is involved in processing of host
      miRNA, hsa-mir-126, that down regulates dengue virus replication. These findings
      suggest a regulatory role of human miRNA pathway especially GRP75 protein and hsa
      mir-126 in dengue virus replication. These results thus provide insights into the
      role of miRNAs and RNAi machinery in dengue life cycle. 

PMID- 27039025
TI  - Streptococcus uberis ST439 and ST475 induce differential inflammatory responses
      in a mouse intramammary infection model.
AB  - Streptococcus uberis causing mastitis is a growing challenge to the dairy
      industry. Molecular, epidemiological and population structure studies have
      revealed clonal diversity among the infecting strains. In this study, mouse
      intramammary infection model was used to uncover the host immune response to two
      epidemiologically important live strains of S. uberis (SU1and SU2) obtained from
      subclinical case of mastitis possessing specific and unique multi locus sequence
      types (ST), pulsed field gel electrophoresis (PFGE) pulsotypes and virulence
      profiles. Temporal (2h, 4h, 8h, 12h, 24h and 48h) expression of key inflammatory
      mediators (IL2, IL4, IL6, IL12, TNFalpha, IFNgamma, GMCSF, TLR2, TLR4, TLR9,
      TLR11, TLR12, CD14, IL1beta, RANTES, Lactoferrin, and CXCl1) by reverse
      transcription and probe-based quantitative real-time PCR showed relative mRNA
      levels higher (p<0.05) in response to SU2 compared with SU1 with 24h PI serving
      as a critical point for the deviating behavior (SU1 versus SU2). Further
      employing the predicted biological processes under the influence of this pool of
      tested genes, the delineation of gene regulatory networks suggested SU1-favoring
      its persistence in the host environment; in contrast, SU2-which elevated gene
      expression indicating towards pathogen clearance or immune surveillance. This
      study suggested how these unique strains could manipulate the host immune
      response to influence the severity of mastitis; our results expand the available
      information on host pathogen interaction and provide a firm foundation needing
      further investigations to gain control over this pathogen.

PMID- 27039026
TI  - Reactive oxygen species in development and infection processes.
AB  - Reactive oxygen species (ROS) are important signaling molecules that affect
      vegetative and pathogenic processes in pathogenic fungi. There is growing
      evidence that ROS are not only secreted during the interaction of host and
      pathogen but also involved in tightly controlled intracellular processes. The
      major ROS producing enzymes are NADPH oxidases (Nox). Recent investigations in
      fungi revealed that Nox-activity is responsible for the formation of infection
      structures, cytoskeleton architecture as well as interhyphal communication.
      However, information about the localization and site of action of the Nox
      complexes in fungi is limited and signaling pathways and intracellular processes
      affected by ROS have not been fully elucidated. This review focuses on the role
      of ROS as signaling molecules in fungal "model" organisms: it examines the role
      of ROS in vegetative and pathogenic processes and gives special attention to Nox
      complexes and their function as important signaling hubs.

PMID- 27039027
TI  - Circadian clocks and the regulation of virulence in fungi: Getting up to speed.
AB  - You cannot escape time. Therefore, it seems wise to learn how to keep track of it
      and use it to your advantage. Circadian clocks are molecular circuits that allow
      organisms to temporally coordinate a plethora of processes, including gene
      expression, with a close to 24h rhythm, optimizing cellular function in synchrony
      with daily environmental cycles. The molecular bases of these clocks have been
      extensively studied in the fungus Neurospora crassa, providing a detailed
      molecular description. Surprisingly, there is scarce molecular information of
      clocks in fungi other than Neurospora, despite the existence of rhythmic
      phenomena in many fungal species, including pathogenic ones. This review will
      comment on the overall importance of clocks, what is known in Neurospora and what
      has been described in other fungi including new insights on the evolution of
      fungal clock components. The molecular description of the circadian system of the
      phytopathogenic fungus Botrytis cinerea will be revisited, as well as time-of-the
      day variation in host-pathogen interaction dynamics, utilizing an Arabidopsis
      Botrytis system, including also what is known regarding circadian regulation of
      defense mechanisms in the Arabidopsis thaliana plant model. Finally, this review
      will mention how little is known about circadian regulation of human pathogenic
      fungi, commenting on potential future directions and the overall perspective of
      fungal circadian studies.

PMID- 27039028
TI  - Pathological and molecular mechanisms underlying resistance to recombinant human
      erythropoietin therapy in the remnant kidney rat model of chronic kidney disease
      associated anemia.
AB  - Anemia of chronic kidney disease (CKD) can be corrected by treatment with
      recombinant human erythropoietin (rHuEPO); however, some patients become
      hyporesponsive. The molecular mechanisms underlying this resistance remain to be
      elucidated. Our aim was to study hyporesponsiveness to rHuEPO therapy using the
      remnant kidney rat model of anemia associated with CKD induced by 5/6
      nephrectomy. At starting, male Wistar rats were divided in 3 groups, for a 3-week
      protocol: Sham, CRF (vehicle) and two rHuEPO (200 k/kg body weight [BW]/week)
      treated groups; at the end of protocol, the rHuEPO treated rats were subdivided
      in responders (CRF200) and non-responders (CRF200NR), according to their
      hematologic response; blood, cellular and tissue studies were performed. The
      CRF200 group achieved correction of anemia, while the CRF200NR group developed
      anemia, after an initial response (1st week) to rHuEPO therapy. CRF and CRF200NR
      groups presented a trend to higher serum CRP levels; CRF200NR showed also high
      levels of renal inflammatory markers, such as interleukin (IL)-6, IL-1beta,
      nuclear factor kappa B, connective tissue growth factor (CTGF) and transforming
      growth factor beta 1 (TGF-beta1); no changes were found in iron metabolism. Our
      data suggest that the development of anemia/rHuEPO hyporesponsiveness is
      associated with a higher systemic and renal inflammatory condition, favoring
      hypoxia and triggering an increase in renal expression of HIF-1alpha, TGF-beta1
      and CTGF that will further aggravate renal fibrosis, which will enhance the
      inflammatory response, creating a cycle that promotes disease progression. New
      therapeutic strategies to reduce inflammation in CKD patients could improve the
      response to rHuEPO therapy and reduce hyporesponsiveness. 

PMID- 27039029
TI  - Comparison of web-based and face-to-face interviews for application to an
      anesthesiology training program: a pilot study.
AB  - OBJECTIVE: This study compared admission rates to a United States anesthesiology
      residency program for applicants completing face-to-face versus web-based
      interviews during the admissions process. We also explored factors driving
      applicants to select each interview type. METHODS: The 211 applicants invited to
      interview for admission to our anesthesiology residency program during the 2014
      2015 application cycle were participants in this pilot observational study. Of
      these, 141 applicants selected face-to-face interviews, 53 applicants selected
      web-based interviews, and 17 applicants declined to interview. Data regarding
      applicants' reasons for selecting a particular interview type were gathered using
      an anonymous online survey after interview completion. Residency program
      admission rates and survey answers were compared between applicants completing
      face-to-face versus web-based interviews. RESULTS: One hundred twenty-seven
      (75.1%) applicants completed face-to-face and 42 (24.9%) completed web-based
      interviews. The admission rate to our residency program was not significantly
      different between applicants completing face-to-face versus web-based interviews.
      One hundred eleven applicants completed post-interview surveys. The most common
      reasons for selecting web-based interviews were conflict of interview dates
      between programs, travel concerns, or financial limitations. Applicants selected
      face-to-face interviews due to a desire to interact with current residents, or
      geographic proximity to the residency program. CONCLUSIONS: These results suggest
      that completion of web-based interviews is a viable alternative to completion of
      face-to-face interviews, and that choice of interview type does not affect the
      rate of applicant admission to the residency program. Web-based interviews may be
      of particular interest to applicants applying to a large number of programs, or
      with financial limitations.

PMID- 27039030
TI  - Occurence of the phthalate esters in soil and street dust samples from the Novi
      Sad city area, Serbia, and the influence on the children's and adults' exposure.
AB  - This is the first study reporting the presence of 6 phthalic acid esters (PAEs)
      in 60 composite soil and street dust samples collected in the urban zone of Novi
      Sad, the second largest city in Serbia. The results were further used to assess
      children's and adults' PAEs nondietary daily intakes (DIs) through incidental
      soil and dust ingestion and/or dermal absorption. The study could be regarded as
      the important baseline for future monitoring of PAEs in the urban environments,
      particularly as it contributes to the rare data on PAEs occurence in the street
      dust. All 6 PAEs were detected in every analyzed soil and street dust samples
      from 0.0002mgkg(-1) to 4.82mgkg(-1), with the highest level obtained for di-(2
      ethylhexyl) phthalate (DEHP), which was the most dominant PAE (70-96%). The
      highest total PAEs (Sigma6PAEs) contents in soil (2.12mgkg(-1)) and street dust
      (5.45mgkg(-1)) samples were obtained for the samples from city parks. In all soil
      samples, Sigma6PAEs exceeded the soil sustainable quality limit sets by the
      relevant Serbian Regulation, but were much lower than the limit requiring
      remediation measures. Concerning the estimated DIs, children were more
      susceptible to PAEs intake than adults regardless of the exposure routes. All the
      estimated DIs values were far below the known reference values.

PMID- 27039031
TI  - Ion and water balance in Gryllus crickets during the first twelve hours of cold
      exposure.
AB  - Insects lose ion and water balance during chilling, but the mechanisms underlying
      this phenomenon are based on patterns of ion and water balance observed in the
      later stages of cold exposure (12 or more hours). Here we quantified the
      distribution of ions and water in the hemolymph, muscle, and gut in adult Gryllus
      field crickets during the first 12h of cold exposure to test mechanistic
      hypotheses about why homeostasis is lost in the cold, and how chill-tolerant
      insects might maintain homeostasis to lower temperatures. Unlike in later chill
      coma, hemolymph [Na(+)] and Na(+) content in the first few hours of chilling
      actually increased. Patterns of Na(+) balance suggest that Na(+) migrates from
      the tissues to the gut lumen via the hemolymph. Imbalance of [K(+)] progressed
      gradually over 12h and could not explain chill coma onset (a finding consistent
      with recent studies), nor did it predict survival or injury following 48h of
      chilling. Gryllus veletis avoided shifts in muscle and hemolymph ion content
      better than Gryllus pennsylvanicus (which is less chill-tolerant), however
      neither species defended water, [Na(+)], or [K(+)] balance during the first 12h
      of chilling. Gryllus veletis better maintained balance of Na(+) content and may
      therefore have greater tissue resistance to ion leak during cold exposure, which
      could partially explain faster chill coma recovery for that species.

PMID- 27039032
TI  - Reproductive arrest and stress resistance in winter-acclimated Drosophila
      suzukii.
AB  - Overwintering insects must survive the multiple-stress environment of winter,
      which includes low temperatures, reduced food and water availability, and cold
      active pathogens. Many insects overwinter in diapause, a developmental arrest
      associated with high stress tolerance. Drosophila suzukii (Diptera:
      Drosophilidae), spotted wing drosophila, is an invasive agricultural pest
      worldwide. Its ability to overwinter and therefore establish in temperate regions
      could have severe implications for fruit crop industries. We demonstrate here
      that laboratory populations of Canadian D. suzukii larvae reared under short-day,
      low temperature, conditions develop into dark 'winter morph' adults similar to
      those reported globally from field captures, and observed by us in southern
      Ontario, Canada. These winter-acclimated adults have delayed reproductive
      maturity, enhanced cold tolerance, and can remain active at low temperatures,
      although they do not have the increased desiccation tolerance or survival of
      fungal pathogen challenges that might be expected from a more heavily melanised
      cuticle. Winter-acclimated female D. suzukii have underdeveloped ovaries and
      altered transcript levels of several genes associated with reproduction and
      stress. While superficially indicative of reproductive diapause, the delayed
      reproductive maturity of winter-acclimated D. suzukii appears to be temperature
      dependent, not regulated by photoperiod, and is thus unlikely to be 'true'
      diapause. The traits of this 'winter morph', however, likely facilitate
      overwintering in southern Canada, and have probably contributed to the global
      success of this fly as an invasive species.

PMID- 27039033
TI  - An evaluation of a family planning mobile job aid for community health workers in
      Tanzania.
AB  - OBJECTIVES: The global rapid growth in mobile technology provides unique
      opportunities to support community health workers (CHWs) in providing family
      planning (FP) services. FHI 360, Pathfinder International and D-tree
      International developed an evidence-based mobile job aid to support CHW
      counseling, screening, service provision and referrals, with mobile forms for
      client and service data, and text-message reporting and reminders. The purpose of
      this study is to evaluate the acceptability and potential benefits to service
      quality from the perspective of CHWs and their clients. STUDY DESIGN: The mobile
      job aid was piloted in Dar es Salaam, Tanzania. Data collection tools included a
      demographic survey of all 25 CHWs trained to use the mobile job aid, in-depth
      interviews with 20 of the CHWs after 3 months and a survey of 176 clients who
      received FP services from a CHW using the mobile job aid after 6 months. RESULTS:
      Both CHWs and their clients reported that the mobile job aid was a highly
      acceptable FP support tool. CHWs perceived benefits to service quality, including
      timelier and more convenient care; better quality of information; increased
      method choice; and improved privacy, confidentiality and trust with clients. Most
      clients discussed multiple FP methods with CHWs; only 1 in 10 clients reported
      discussion of all 9 methods. CONCLUSIONS: This research suggests that mobile
      phones can be effective tools to support CHWs with FP counseling, screening and
      referrals, data collection and reporting, and communication. Challenges remain to
      support informed contraceptive choice. Future research should focus on
      implementation, including scale-up and sustainability. IMPLICATIONS: Mobile job
      aids can uniquely enhance FP service provision at the community level through
      adherence to standard protocols, real-time feedback and technical assistance, and
      provision of confidential care. This study can inform future efforts to support
      and expand the role of CHWs in increasing FP access and informed contraceptive
      choice.

PMID- 27039034
TI  - Editorial - A critical perspective on geo-engineering for eutrophication
      management in lakes.
AB  - Eutrophication is the primary worldwide water quality issue. Reducing excessive
      external nutrient loading is the most straightforward action in mitigating
      eutrophication, but lakes, ponds and reservoirs often show little, if any, signs
      of recovery in the years following external load reduction. This is due to
      internal cycling of phosphorus (P). Geo-engineering, which we can here define as
      activities intervening with biogeochemical cycles to control eutrophication in
      inland waters, represents a promising approach, under appropriate conditions, to
      reduce P release from bed sediments and cyanobacteria accumulation in surface
      waters, thereby speeding up recovery. In this overview, we draw on evidence from
      this special issue Geoengineering in Lakes, and on supporting literature to
      provide a critical perspective on the approach. We demonstrate that many of the
      strong P sorbents in the literature will not be applicable in the field because
      of costs and other constraints. Aluminium and lanthanum modified compounds are
      among the most effective compounds for targeting P. Flocculants and ballast
      compounds can be used to sink cyanobacteria, in the short term. We emphasize that
      the first step in managing eutrophication is a system analysis that will reveal
      the main water and P flows and the biological structure of the waterbody. These
      site specific traits can be significant confounding factors dictating successful
      eutrophication management. Geo-engineering techniques, considered collectively,
      as part of a tool kit, may ensure successful management of eutrophication through
      a range of target effects. In addition, novel developments in modified zeolites
      offer simultaneous P and nitrogen control. To facilitate research and reduce the
      delay from concept to market a multi-national centre of excellence is required.

PMID- 27039035
TI  - Inhibition of alpha oscillations through serotonin-2A receptor activation
      underlies the visual effects of ayahuasca in humans.
AB  - Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two
      plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic
      5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus beta-carboline
      alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the
      psychoactive effects of ayahuasca have commonly been attributed solely to agonism
      at the 5-HT2A receptor, the molecular target of classical psychedelics, this has
      not been tested experimentally. Here we wished to study the contribution of the 5
      HT2A receptor to the neurophysiological and psychological effects of ayahuasca in
      humans. We measured drug-induced changes in spontaneous brain oscillations and
      subjective effects in a double-blind randomized placebo-controlled study
      involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and
      the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic
      users (5 females) participated in four experimental sessions in which they
      received the following drug combinations: placebo+placebo, placebo+ayahuasca,
      ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power
      decreases in the delta, theta and alpha frequency bands. Current density in alpha
      band oscillations in parietal and occipital cortex was inversely correlated with
      the intensity of visual imagery induced by ayahuasca. Pretreatment with
      ketanserin inhibited neurophysiological modifications, reduced the correlation
      between alpha and visual effects, and attenuated the intensity of the subjective
      experience. These findings suggest that despite the chemical complexity of
      ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and
      visual effects of ayahuasca in humans.

PMID- 27039036
TI  - Affective responsiveness is influenced by intake of oral contraceptives.
AB  - Despite the widespread use of oral contraceptive pills (OCs), little is known
      about their impact on psychological processes and emotional competencies. Recent
      data indicate impaired emotion recognition in OC users compared to naturally
      cycling females. Building upon these findings, the current study investigated the
      influence of OC use on three components of empathy, i.e., emotion recognition,
      perspective-taking, and affective responsiveness. We compared naturally cycling
      women to two groups of OC users, one being tested in their pill-free week and one
      in the phase of active intake. Whereas groups did not differ in emotion
      recognition and perspective-taking, an effect of pill phase was evident for
      affective responsiveness: Females currently taking the pill showed better
      performance than those in their pill-free week. These processing advantages
      complement previous findings on menstrual cycle effects and thereby suggest an
      association with changes in endogenous and exogenous reproductive hormones. The
      current study highlights the need for future research to shed more light on the
      neuroendocrine alterations accompanying OC intake.

PMID- 27039037
TI  - Chronic expression of Ski induces apoptosis and represses autophagy in cardiac
      myofibroblasts.
AB  - Inappropriate cardiac interstitial remodeling is mediated by activated
      phenoconverted myofibroblasts. The synthesis of matrix proteins by these cells is
      triggered by both chemical and mechanical stimuli. Ski is a repressor of
      TGFbeta1/Smad signaling and has been described as possessing anti-fibrotic
      properties within the myocardium. We hypothesized that overexpression of Ski in
      myofibroblasts will induce an apoptotic response, which may either be supported
      or opposed by autophagic flux. We used primary myofibroblasts (activated
      fibroblasts) which were sourced from whole heart preparations that were only
      passaged once. We found that overexpression of Ski results in distinct
      morphological and biochemical changes within primary cardiac myofibroblasts
      associated with apoptosis. Ski treatment was associated with the expression of
      pro-apoptotic factors such as Bax, caspase-7, and -9. Our results indicate that
      Ski triggers a pro-death mechanism in primary rat cardiac myofibroblasts that is
      mediated through the intrinsic apoptotic pathway. Myofibroblast survival is
      prolonged by an autophagic response, as the dataset indicate that apoptosis is
      hastened when autophagy is inhibited. We suggest that the apoptotic death
      response of myofibroblasts is working in parallel with the previously observed
      anti-fibrotic properties of Ski within this cell type. As myofibroblasts are the
      sole mediators of matrix expansion in heart failure, we suggest that Ski, or a
      putative Ski-mimetic, may induce graded apoptosis in myofibroblasts within the
      failing heart and may be a novel therapeutic approach towards controlling cardiac
      fibrosis. Future studies are needed to examine the potential effects of Ski
      overexpression on other cell types in the heart. 

PMID- 27039038
TI  - The Sumo protease Senp7 is required for proper neuronal differentiation.
AB  - Covalent attachment of the Small ubiquitin-like modifier (Sumo) polypeptide to
      proteins regulates many processes in the eukaryotic cell. In the nervous system,
      Sumo has been associated with the synapsis and with neurodegenerative diseases.
      However, its involvement in regulating neuronal differentiation remains largely
      unknown. Here we show that net Sumo deconjugation is observed during neurogenesis
      and that Sumo overexpression impairs this process. In an attempt to shed light on
      the underlying mechanisms, we have analyzed the expression profile of genes
      coding for components of the sumoylation pathway following induction of neuronal
      differentiation. Interestingly, we observed strong upregulation of the Senp7
      protease at both mRNA and protein levels under differentiation conditions. Sumo
      proteases, by removing Sumo from targets, are key regulators of sumoylation.
      Strikingly, loss-of-function analysis demonstrated that Senp7 is required for
      neuronal differentiation not only in a model cell line, but also in the
      developing neural tube. Finally, reporter-based analysis of the Senp7 promoter
      indicated that Senp7 was transiently activated at early stages of neuronal
      differentiation. Thus, the Sumo protease Senp7 adds to the list of factors
      involved in vertebrate neurogenesis. 

PMID- 27039039
TI  - Apportioning blame in the North American hepatitis C virus epidemic.

PMID- 27039040
TI  - The spread of hepatitis C virus genotype 1a in North America: a retrospective
      phylogenetic study.
AB  - BACKGROUND: The timing of the initial spread of hepatitis C virus genotype 1a in
      North America is controversial. In particular, how and when hepatitis C virus
      reached extraordinary prevalence in specific demographic groups remains unclear.
      We quantified, using all available hepatitis C virus sequence data and
      phylodynamic methods, the timing of the spread of hepatitis C virus genotype 1a
      in North America. METHODS: We screened 45 316 publicly available sequences of
      hepatitis C virus genotype 1a for location and genotype, and then did
      phylogenetic analyses of available North American sequences from five hepatitis C
      virus genes (E1, E2, NS2, NS4B, NS5B), with an emphasis on including as many
      sequences with early collection dates as possible. We inferred the historical
      population dynamics of this epidemic for all five gene regions using Bayesian
      skyline plots. FINDINGS: Most of the spread of genotype 1a in North America
      occurred before 1965, and the hepatitis C virus epidemic has undergone relatively
      little expansion since then. The effective population size of the North American
      epidemic stabilised around 1960. These results were robust across all five gene
      regions analysed, although analyses of each gene separately show substantial
      variation in estimates of the timing of the early exponential growth, ranging
      roughly from 1940 for NS2, to 1965 for NS4B. INTERPRETATION: The expansion of
      genotype 1a before 1965 suggests that nosocomial or iatrogenic factors rather
      than past sporadic behavioural risk (ie, experimentation with injection drug use,
      unsafe tattooing, high risk sex, travel to high endemic areas) were key
      contributors to the hepatitis C virus epidemic in North America. Our results
      might reduce stigmatisation around screening and diagnosis, potentially
      increasing rates of screening and treatment for hepatitis C virus. FUNDING: The
      Canadian Institutes of Health Research, Michael Smith Foundation for Health
      Research, and BC Centre for Excellence in HIV/AIDS.

PMID- 27039041
TI  - The 5-HT6 receptor antagonist idalopirdine potentiates the effects of
      acetylcholinesterase inhibition on neuronal network oscillations and
      extracellular acetylcholine levels in the rat dorsal hippocampus.
AB  - The 5-HT6 receptor has emerged as a promising target for cognitive disorders and
      combining a 5-HT6 receptor antagonist with an acetylcholinesterase inhibitor
      (AChEI) represents a novel approach for the symptomatic treatment of Alzheimer's
      disease (AD). A recent phase 2 trial showed that the selective 5-HT6 receptor
      antagonist idalopirdine (Lu AE58054) improved cognition in patients with moderate
      AD on stable treatment with the AChEI donepezil. Here we investigated the effects
      of idalopirdine in combination with donepezil on hippocampal function using in
      vivo electrophysiology and microdialysis. Network oscillations in the hippocampus
      were recorded during electrical stimulation of the brainstem nucleus pontis
      oralis (nPO) in the anesthetized rat and hippocampal acetylcholine (ACh) levels
      were measured in the freely-moving rat. In addition, potential pharmacokinetic
      interactions between idalopirdine and donepezil were assessed. Idalopirdine alone
      did not affect hippocampal network oscillations or ACh levels. Donepezil (0.3 and
      1.0 mg/kg i.v.) dose-dependently increased hippocampal theta and gamma power
      during nPO stimulation. Idalopirdine (2 mg/kg i.v.), administered 1 h prior to
      donepezil, potentiated the theta and gamma response to 0.3 mg/kg donepezil and
      prolonged the gamma response to 1 mg/kg donepezil. Donepezil (1.3 mg/kg s.c.)
      increased extracellular ACh levels in the hippocampus and this was further
      augmented by administration of idalopirdine (10 mg/kg p.o.) 2 h prior to
      donepezil. These effects could not be attributed to a pharmacokinetic interaction
      between the compounds. This study demonstrates that idalopirdine potentiates the
      effects of donepezil on two pharmacodynamic biomarkers associated with cognition,
      i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such
      potentiation could contribute to the procognitive effects of idalopirdine
      observed in donepezil-treated AD patients.

PMID- 27039042
TI  - Differential efficacy of the TSPO ligands etifoxine and XBD-173 in two rodent
      models of Multiple Sclerosis.
AB  - Neurosteroids such as progesterone and allopregnanolone have been shown to exert
      neuroprotective effects under a variety of pathological or insult conditions, and
      there is evidence that the neurosteroid system is perturbed in Multiple Sclerosis
      (MS) patients. Neurosteroids are synthesized in the central nervous system (CNS)
      through a series of metabolic transformations, beginning with a rate-limiting
      step of cholesterol transport through the outer mitochondrial membrane via the
      transporter translocator protein (TSPO). We examined the effects of etifoxine and
      XBD-173, two different brain penetrant TSPO agonists, for their ability to
      ameliorate clinical signs in two different experimental autoimmune encephalitis
      (EAE) models. Etifoxine, as previously reported, was efficacious in EAE, while
      XBD-173 was not. Surprisingly, XBD-173, but not etifoxine elevated relevant
      neurosteroids in brain of female rats and differed in its ability to exert anti
      inflammatory and direct neuroprotective effects in vitro as compared to
      etifoxine. We conclude that the neurosteroid elevations produced in brain by XBD
      173 are not sufficient to ameliorate EAE and suggest that etifoxine may have
      additional mechanisms of action that provide therapeutic benefit in this model
      system.

PMID- 27039043
TI  - Progesterone in the treatment of neonatal arterial ischemic stroke and acute
      seizures: Role of BDNF/TrkB signaling.
AB  - Neonatal stroke is among the top ten causes of childhood death and permanent
      disability in survivors, but no safe and effective acute treatments exist. To
      advance understanding of its neuroprotective mechanisms, we examined the effects
      of progesterone (PROG) on local and systemic inflammation (IL-1beta, IL-6,
      TNFalpha), brain derived neurotrophic factor/Tropomyosin receptor kinase B
      (BDNF/TrkB) signaling, vascular damage (vascular endothelial growth factor
      (VEGF), matrix metalloproteinase-9 (MMP-9)), acute behavioral seizures and brain
      infarction size following neonatal arterial ischemic stroke in mice. CD1 mouse
      pups (postnatal day 12, mixed gender) received permanent unilateral right common
      carotid ligation (pUCCL) or sham surgery. Pups showing seizure activity during
      the first hour post-pUCCL were randomly assigned to receive PROG (8 mg/kg) or
      vehicle injections. PROG treatment significantly (p < 0.05) reduced seizure
      occurrence by ~44% compared to vehicle and attenuated the expression of pro
      inflammatory cytokines in serum and brain at different time-points. PROG
      differentially regulated the expression of BDNF and TrkB and the activity of VEGF
      and MMP-9 over the 7d period. Permanent UCCL resulted in severe hemispheric
      damage measured at 7 days post-pUCCL but PROG treatment produced a significant (p
      < 0.05) reduction in infarct volume (~70%) compared to vehicle. A gender-based
      comparison of data revealed significantly greater seizure activity in males
      compared to females. However, we did not observe significant sex differences on
      any other markers of the injury at this early stage of development. PROG
      treatment is neuroprotective through a number of signaling pathways and can be
      beneficial in treating neonatal arterial ischemic stroke in CD1 mice.

PMID- 27039044
TI  - Evidence From Pacing in Obstructive Hypertrophic Cardiomyopathy. Response.

PMID- 27039045
TI  - Evidence From Pacing in Obstructive Hypertrophic Cardiomyopathy.

PMID- 27039046
TI  - The spatial distribution of gender differences in obesity prevalence differs from
      overall obesity prevalence among US adults.
AB  - PURPOSE: Although obesity disparities between racial and socioeconomic groups
      have been well characterized, those based on gender and geography have not been
      as thoroughly documented. This study describes obesity prevalence by state,
      gender, and race and/or ethnicity to (1) characterize obesity gender inequality,
      (2) determine if the geographic distribution of inequality is spatially
      clustered, and (3) contrast the spatial clustering patterns of obesity gender
      inequality with overall obesity prevalence. METHODS: Data from the Centers for
      Disease Control and Prevention's 2013 Behavioral Risk Factor Surveillance System
      were used to calculate state-specific obesity prevalence and gender inequality
      measures. Global and local Moran's indices were calculated to determine spatial
      autocorrelation. RESULTS: Age-adjusted, state-specific obesity prevalence
      difference and ratio measures show spatial autocorrelation (z-score = 4.89, P
      value < .001). Local Moran's indices indicate the spatial distributions of
      obesity prevalence and obesity gender inequalities are not the same. High and low
      values of obesity prevalence and gender inequalities cluster in different areas
      of the United States. CONCLUSIONS: Clustering of gender inequality suggests that
      spatial processes operating at the state level, such as occupational or physical
      activity policies or social norms, are involved in the etiology of the inequality
      and necessitate further attention to the determinates of obesity gender
      inequality.

PMID- 27039048
TI  - Vaginal fluid pH and buffer capacity for predicting false preterm labor in
      Japanese women.
AB  - OBJECTIVE: To determine the relationship between preterm labor and delivery, and
      the pH and buffer capacity of vaginal secretions. METHODS: Between January 1,
      2009 and March 31, 2012, two cohorts of patients at 22-36weeks of pregnancy were
      enrolled in a prospective cohort study at Nara Medical University Hospital,
      Japan. Patients experiencing preterm contractions and a control group of patients
      experiencing normal pregnancies were included. The pH and buffer capacity of
      vaginal secretions were measured and compared. RESULTS: Of the 237 patients
      enrolled, 48 (20.3%) were experiencing symptoms of preterm labor and 189 (79.7%)
      were included in the control group. The pH was higher (P<0.001) and the buffer
      capacity was lower (P=0.0135) in the vaginal secretions of the patients
      experiencing preterm contractions compared with the control group. There was no
      difference in the pH and buffer capacity of the vaginal secretions of symptomatic
      patients who would experience preterm delivery and those who would not. Receiver
      operating characteristic curve analyses demonstrated that vaginal-secretion pH
      and buffer capacity could differentiate between patients experiencing preterm
      contractions and those not, but could not differentiate between patients who
      would experience preterm delivery and those who would not. CONCLUSION: Vaginal
      secretion pH and buffer capacity could be useful in diagnosing preterm labor;
      further studies are needed to determine potential practical diagnostic criteria.

PMID- 27039047
TI  - Characterization of the gut microbiome in epidemiologic studies: the multiethnic
      cohort experience.
AB  - PURPOSE: The development of next-generation sequencing and accompanying
      bioinformatics tools has revolutionized characterization of microbial
      communities. As interest grows in the role of the human microbiome in health and
      disease, so does the need for well-powered, robustly designed epidemiologic
      studies. Here, we discuss sources of bias that can arise in gut microbiome
      research. METHODS: Research comparing methods of specimen collection,
      preservation, processing, and analysis of gut microbiome samples is reviewed.
      Although selected studies are primarily based on the gut, many of the same
      principles are applicable to samples derived from other anatomical sites. Methods
      for participant recruitment and sampling of the gut microbiome implemented in an
      ongoing population-based study, the Multiethnic Cohort (MEC), are also described.
      RESULTS: Variation in methodologies can influence the results of human microbiome
      studies. To help minimize bias, techniques such as sample homogenization,
      addition of internal standards, and quality filtering should be adopted in
      protocols. Within the MEC, participant response rates to stool sample collection
      were comparable to other studies, and in-home stool sample collection yields
      sufficient high-quality DNA for gut microbiome analysis. CONCLUSIONS: Application
      of standardized and quality controlled methods in human microbiome studies is
      necessary to ensure data quality and comparability among studies.

PMID- 27039049
TI  - Association between the maternal serum levels of 19 eicosanoids and pre
      eclampsia.
AB  - OBJECTIVE: To investigate whether serum levels of 19 eicosanoids are associated
      with pre-eclampsia. METHODS: A case-control study was performed using data for
      pregnant women with pre-eclampsia, normotensive pregnant women, and nonpregnant
      women, for all of whom serum samples had been collected at a hospital in
      Shanghai, China, between December 2012 and December 2013. Ultra-performance
      liquid chromatography-tandem mass spectrometry was used to measure the serum
      levels of 19 eicosanoids. RESULTS: Overall, 49 pregnant women with pre-eclampsia,
      26 normotensive pregnant women, and 14 nonpregnant women were included. Women
      with pre-eclampsia had significantly higher serum levels of 11,12
      epoxyeicosatrienoic acid (11,12-EET), the hydroxyeicosatetraenoic acids 5-HETE, 8
      HETE, 12-HETE, and 15-HETE, and leukotriene B4 than did women with a normal
      pregnancy and nonpregnant women, both before and after the onset of pre-eclampsia
      (P<0.01 for all comparisons). Women with severe pre-eclampsia had significantly
      higher serum levels of 5-HETE, 15-HETE, and leukotriene B4 than did women with
      mild pre-eclampsia, women with a normal pregnancy, and nonpregnant women (P<0.01
      for all comparisons). CONCLUSION: The eicosanoids 11,12-EET, 5-HETE, 8-HETE, 12
      HETE, 15-HETE, and leukotriene B4 might play important parts in the occurrence
      and development of pre-eclampsia.

PMID- 27039050
TI  - Ensuring best decisions in women's health.

PMID- 27039051
TI  - Variable genetic penetrance of myotonic dystrophy following the diagnosis of
      idiopathic polyhydramnios.

PMID- 27039052
TI  - Outcomes of fertility-sparing surgery among young women with FIGO stage I clear
      cell carcinoma of the ovary.
AB  - OBJECTIVES: To evaluate the outcome of fertility-sparing surgery among young
      women with early-stage clear cell carcinoma of the ovary. METHODS: In a
      retrospective study, data were reviewed for patients aged 45years or younger who
      had FIGO stage I clear cell carcinoma of the ovary and had attended one
      institution in South Korea between December 1999 and December 2009. Outcomes were
      compared between women undergoing fertility-sparing surgery, defined as
      preservation of the uterus and at least one adnexa, and those undergoing radical
      surgery. RESULTS: Overall, 47 patients were included (22 underwent fertility
      sparing surgery, 25 radical surgery). After a median follow-up of 72months (range
      8-175), 5 (23%) patients who underwent fertility-sparing surgery and 5 (20%) in
      the radical surgery group had recurrent disease (P=0.820). The mean time to
      recurrence was 19months after fertility-sparing surgery versus 20months after
      radical surgery (P=0.935). The anatomical location of recurrence did not differ.
      There was no difference in 5-year disease-free survival (77% vs 84%; P=0.849) or
      5-year overall survival (91% vs 88%; P=0.480). CONCLUSION: Fertility-sparing
      surgery was found to be a safe alternative for young women with FIGO stage I
      clear cell carcinoma of the ovary who wish to preserve fertility.

PMID- 27039053
TI  - A systematic review and meta-analysis of intimate partner violence during
      pregnancy and selected birth outcomes.
AB  - BACKGROUND: Intimate partner violence (IPV) has a detrimental impact on the lives
      of women worldwide. Several studies have examined the effect IPV has on adverse
      birth outcomes when it occurs during pregnancy. OBJECTIVES: To explore the
      association between IPV and selected adverse birth outcomes. SEARCH STRATEGY:
      Multiple databases were searched to identify studies investigating the
      association between IPV and low birth weight (LBW), preterm birth, and/or
      intrauterine growth restriction (IUGR). SELECTION CRITERIA: Included studies
      defined the perpetrator of violence as an intimate partner, the type of violence
      as physical and/or sexual, and the study outcomes as LBW, preterm birth, or IUGR,
      with violence preceding delivery. DATA COLLECTION AND ANALYSIS: Random-effects
      meta-analysis was used to calculate adjusted/unadjusted odds ratios (ORs).
      Subanalyses explored the effect of emotional/psychological violence on birth
      outcomes. MAIN RESULTS: Nineteen studies met the inclusion criteria (15 LBW, 12
      preterm birth, 4 IUGR). IPV was associated with LBW (OR 1.18, 95% confidence
      interval 1.05-1.31; I(2)=0.70, P<0.001) and preterm birth (OR 1.42, 95%
      confidence interval 1.21-1.63; I(2)=0.20, P<0.001). No statistically significant
      association was found for IUGR. CONCLUSIONS: There are associations between IPV
      and LBW and preterm birth that could be causal.

PMID- 27039054
TI  - A systematic review of ultrasonography-guided transvaginal aspiration of
      recurrent ovarian endometrioma.
AB  - BACKGROUND: Ovarian endometriosis is present in 17%-44% of women with
      endometriosis. The main treatment is surgery, but ultrasonography-guided
      aspiration is a less invasive alternative. OBJECTIVES: To evaluate the
      effectiveness of this alternative treatment in recurrent ovarian endometrioma.
      SEARCH STRATEGY: Multiple databases were searched for articles published between
      1994 and 2014 using the keywords "ultrasound-guided aspiration," "ovarian," and
      "endometriosis." SELECTION CRITERIA: Randomized controlled trials and
      observational studies published in English, Portuguese, or Spanish were included.
      DATA COLLECTION AND ANALYSIS: Two researchers independently extracted and
      reviewed the data. The main outcome of interest was the recurrence rate. MAIN
      RESULTS: Eight studies were eligible. Ovarian endometriosis is associated with
      high recurrence rates after one ultrasonography-guided aspiration (28.9%-91.5%),
      but involves less ovarian manipulation. The results of aspiration followed by
      sclerotherapy are not uniform, but overall the addition of a sclerosing agent
      does not seem to significantly reduce the likelihood of recurrence (13.3%-75.0%).
      Repeated aspiration of the cysts can reduce the recurrence rate to 5.4% by the
      sixth aspiration. CONCLUSIONS: Repeated ultrasonography-guided aspiration of
      ovarian endometriomas can be performed for the treatment of recurrent ovarian
      endometriosis. Further studies comparing the efficacy of this procedure and
      ovarian surgery are needed.

PMID- 27039055
TI  - Loss of ATP13A2 impairs glycolytic function in Kufor-Rakeb syndrome patient
      derived cell models.
AB  - BACKGROUND: Kufor-Rakeb syndrome (KRS) is an autosomal recessive, juvenile-onset
      Parkinson's disease (PD) caused by loss-of-function mutations in ATP13A2 (PARK9).
      Impaired energy metabolism is considered a pathogenic mechanism in PD and
      mitochondrial dysfunction resulting from Zn(2+) dyshomeostasis has been found in
      KRS patient-derived cells. In addition to mitochondrial energy production,
      glycolysis plays an important role in cellular energy metabolism and glucose
      hypometabolism has been reported in PD. However, glycolytic status in KRS remains
      undetermined despite its potential importance. METHODS: We assessed glycolytic
      function in ATP13A2-deficient KRS patient-derived human olfactory neurosphere
      cells and fibroblasts and determined the effect of pyruvate supplementation on
      improving cellular energy production. RESULTS: We found impaired extracellular
      acidification, reduction in pyruvate production and a decrease in the NAD(+)/NADH
      ratio, indicative of glycolytic dysfunction. In addition, gene expression
      analysis revealed an altered expression profile for several glycolytic enzymes.
      Glycolytic dysfunction was aggravated when the intracellular Zn(2+) concentration
      was increased, while ATP13A2 overexpression and pyruvate supplementation blocked
      the observed Zn(2+)-mediated toxicity. Moreover, supplementation with pyruvate
      significantly increased basal mitochondrial ATP production and abolished Zn(2+)
      induced cell death. CONCLUSIONS: These findings indicate that glycolytic
      dysfunction contributes to pathogenesis and pyruvate supplementation improves
      overall cellular bioenergetics in our KRS patient-derived cell model,
      highlighting a therapeutic potential.

PMID- 27039056
TI  - Tremor in progressive supranuclear palsy.
AB  - INTRODUCTION: Tremor is thought to be a rare feature of progressive supranuclear
      palsy (PSP). METHODS: We retrospectively reviewed the database of the CurePSP
      brain bank at Mayo Clinic Florida to retrieve all available clinical information
      for PSP patients. All patients underwent a standard neuropathological assessment
      and an immunohistochemical evaluation for tau and alpha-synuclein. DNA was
      genotyped for the MAPT H1/H2 haplotype. RESULTS: Of the 375 PSP patients
      identified, 344 had a documented presence or absence of tremor, which included
      146 (42%) with tremor, including 29 (20%) with postural/action tremors, 16 (11%)
      with resting tremor, 7 (5%) with intention tremor, 20 (14%) with a combination of
      different types of tremor, and 74 (51%) patients who had tremor at some point
      during their illness, but details were unavailable. The tremor severity of 96% of
      the patients (54/55) who had this data was minimal to mild. The probability of
      observing a tremor during a neurological examination during the patient's illness
      was estimated to be ~22%. PSP patients with postural/action tremors and PSP
      patients with resting tremor responded to carbidopa-levodopa therapy more
      frequently than PSP patients without tremor, although the therapy response was
      always transient. There were no significant differences in pathological findings
      between the tremor groups. CONCLUSIONS: Tremor is an inconspicuous feature of
      PSP; however, 42% (146/344) of the PSP patients in our study presented some form
      of tremor. Because there is no curative therapy for PSP, carbidopa/levodopa
      therapy should be tried for patients with postural, action, and resting tremor.

PMID- 27039057
TI  - A chromatin modifier integrates insulin/IGF-1 signalling and dietary restriction
      to regulate longevity.
AB  - Insulin/IGF-1-like signalling (IIS) and dietary restriction (DR) are the two
      major modulatory pathways controlling longevity across species. Here, we show
      that both pathways license a common chromatin modifier, ZFP-1/AF10. The
      downstream transcription factors of the IIS and select DR pathways, DAF-16/FOXO
      or PHA-4/FOXA, respectively, both transcriptionally regulate the expression of
      zfp-1. ZFP-1, in turn, negatively regulates the expression of DAF-16/FOXO and PHA
      4/FOXA target genes, apparently forming feed-forward loops that control the
      amplitude as well as the duration of gene expression. We show that ZFP-1 mediates
      this regulation by negatively influencing the recruitment of DAF-16/FOXO and PHA
      4/FOXA to their target promoters. Consequently, zfp-1 is required for the
      enhanced longevity observed during DR and on knockdown of IIS. Our data reveal
      how two distinct sensor pathways control an overlapping set of genes, using
      different downstream transcription factors, integrating potentially diverse and
      temporally distinct nutritional situations.

PMID- 27039058
TI  - Outcomes and Lessons Learned From a Randomized Controlled Trial to Reduce Health
      Care Utilization During the First Year After Spinal Cord Injury Rehabilitation:
      Telephone Counseling Versus Usual Care.
AB  - OBJECTIVES: To describe the outcomes and lessons learned from a trial of
      telephone counseling (TC) to reduce medical complications and health care
      utilization and to improve psychosocial outcomes during the first year after
      spinal cord injury rehabilitation. DESIGN: Single-site, single-blind, randomized
      (1:1) controlled trial comparing usual care plus TC with usual care (UC).
      SETTING: Two inpatient rehabilitation programs. PARTICIPANTS: Adult patients
      (N=168) discharged between 2007 and 2010. INTERVENTIONS: The TC group (n=85, 51%)
      received up to eleven 30- to 45-minute scheduled telephone calls to provide
      education, resources, and support. The UC group (n=83, 49%) received indicated
      referrals and treatment. MAIN OUTCOME MEASURES: The primary outcome was a
      composite of self-reported health care utilization and medical complications.
      Secondary outcomes were depression severity, current health state, subjective
      health, and community participation. RESULTS: No significant differences were
      observed between TC and UC groups in the primary or secondary psychosocial
      outcomes. CONCLUSIONS: This study had a number of strengths, but included
      potential design weaknesses. Intervention studies would benefit from prescreening
      participants to identify those with treatable problems, those at high risk for
      poor outcomes, or those with intentions to change target behaviors. Interventions
      focused on treatment goals and designed to work in collaboration with the
      participant's medical care system may lead to improved outcomes.

PMID- 27039059
TI  - Effects of rigorous emission controls on reducing ambient volatile organic
      compounds in Beijing, China.
AB  - 102 volatile organic compound (VOC) species were measured online using a gas
      chromatography-mass spectrometry/flame ionization detector (GC-MS/FID) at an
      urban site in Beijing in 11 August to 3 September 2015, when a series of rigorous
      air quality control measures were implemented in Beijing city and neighbouring
      provinces. Positive matrix factorization (PMF) was applied to identify emission
      sources from 1h averaged values of VOC data. Based on the online VOC data and the
      PMF analysis results, the effectiveness of different control measures were
      investigated. The PMF results were compared with an emission inventory data.
      Results show that the rigorous air quality restrictions implemented were
      successful. The averaged ambient VOC mixing ratios during the emission control
      period and non-control period were 27.53 and 45.42ppbv, respectively. The mixing
      ratios of total VOC during the control period were reduced by 40%. Alkanes were
      the most abundant chemical group in the two periods, followed by oxygenated
      volatile organic compounds (OVOCs). Almost all quantified VOC species decreased
      during the control period. Tracers of industrial sources and vehicle exhaust
      reduced most, including some halocarbons, esters and aromatics. Eight sources
      were resolved by online PMF analysis for ambient VOCs in Beijing. Contributions
      of those sources varied significantly during the control and non-control period.
      Compared with the values before control, contributions of vehicle-related sources
      were most reduced, followed by solvent utilization. Reductions of vehicle-related
      sources, solvent utilization, secondary formation, fuel combustion, and biogenic
      were responsible for 65%, 19%, 10%, 5%, and 1% of the reductions in ambient VOCs.
      Both PMF results and emission inventory data indicated that the control measure
      on traffic was very effective in reducing ambient VOCs in Beijing, with the
      emission reductions of about 50%.

PMID- 27039060
TI  - Fast analysis of 4-tertoctylphenol, pentachlorophenol and 4-nonylphenol in river
      sediments by QuEChERS extraction procedure combined with GC-QqQ-MS/MS.
AB  - A quick, easy, cheap, effective, rugged and safe (QuEChERS)-based extraction
      method has been optimized for the determination of pentachlorophenol, 4
      tertoctylphenol and 4-nonylphenol in river sediments. The extraction method was
      followed by gas chromatography-triple quadrupole tandem mass spectrometry (GC-QqQ
      MS/MS) analysis, which ensures the reliable identification of the target
      compounds. The proposed method has been validated allowing the successful
      determination of the selected compounds, with recoveries ranging from 72 to 96%,
      when three concentration levels were evaluated (10, 50 and 100MUgkg(-1)) and
      inter-day and intra-day precision, expressed as relative standard deviation
      (RSD), were lower than 20%. The method showed limits of detection (LODs) and
      limits of quantification (LOQs) ranging from 0.1 to 2.0MUgkg(-1) and from 0.5 to
      5.0MUgkg(-1), respectively. Finally, 25 real samples from Poland have been
      analyzed, and only 4-tertoctylphenol was detected at concentrations up to
      8.9MUgkg(-1) of soil dry weight.

PMID- 27039061
TI  - Effects of illuminance and nutrients on bacterial photo-physiology of hydrocarbon
      degradation.
AB  - Bacterial photophysiology was previously limited to photoautotrophs. The
      discovery of bacteriophytochromes in non-photoautotrophs raised a question
      whether these non-photoautotrophs are affected by the presence or absence of
      light? In this research work for the first time, bacterial hydrocarbon
      degradation and biomass production was studied under the influence of nutrients,
      illuminance (light flux) and time. An experimental model was designed, with six
      isolated bacterial strains (Pseudomonas poae BA1, Pseudomonas rhizosphaerae BP3,
      Bacillus thuringiensis BG3, Acinetobacter bouvetii BP18, Pseudomonas proteolytica
      BG31 and Stenotrophomonas rhizophila BG32) under four different conditions of
      nutrient media and illuminance at three time intervals of 15, 30, and 45days
      without shaking. All strains showed statistically higher hydrocarbon degradation
      under nutrient rich, dark conditions. Highest biodegradation (80.8, 79.4, and
      78.7mg) was observed in BG31, BG17 and BG3 respectively. Nutrient rich media
      along with dark conditions improved the biomass production, and when media was
      nutrient deprived, higher biomass was produced in the presence of light. This
      work proved that light and nutrients significantly affect bacterial populations
      and hydrocarbon degradation. The optimal use of these parameters could facilitate
      to achieve the goal of remediation of hydrocarbon contaminated sites.

PMID- 27039062
TI  - Remediation of mercury contaminated saltwater with functionalized silica coated
      magnetite nanoparticles.
AB  - The study aimed to evaluate the efficiency of dithiocarbamate functionalized
      silica coated magnetite nanoparticles (NPs) for Hg decontamination of saltwater
      either contaminated with Hg alone or with As and Cd. For this, the residual
      levels of Hg in seawater were assessed and Hg-contaminated or Hg+As+Cd
      contaminated seawater toxicity to aquatic biota, before and after the sorption
      process, was compared. The results showed that under highly competitive
      conditions (water salts, Cd and As), the removal of Hg from seawater, by using
      these magnetic NPs, for the lowest concentration (50MUg/L) was superior to 98%
      and for the highest concentration (500MUg/L) ranged between 61% to 67%. Despite
      the great affinity of the magnetic NPs for Hg, they were not effective at
      removing As and Cd from seawater. In relation to the ecotoxicity endpoints after
      remediation, the mixture with lower Hg concentration exhibited no toxicity to
      rotifer Brachionus plicatilis and bacteria Vibrio fischeri ; however, the mixture
      with higher concentration revealed toxicity. In addition, the toxicity of
      bacteria V. fischeri, rotifer B. plicatilis and algae Phaeodactylum tricornutum,
      whose responses where inhibited during its exposure to the non-remediate sample
      was considerably reduced after treatment with NPs. Furthermore, microalgae P.
      tricornutum appears to be most sensitive species while Artemia franciscana showed
      no toxic effects to the tested solutions. Both chemical and ecotoxicological
      approaches revealed a high efficiency for the remediation of Hg-contaminated
      saltwater.

PMID- 27039063
TI  - Biodegradation of carbamazepine and clarithromycin by Trichoderma harzianum and
      Pleurotus ostreatus investigated by liquid chromatography - high-resolution
      tandem mass spectrometry (FTICR MS-IRMPD).
AB  - In this study, the capability of pharmaceutical biodegradation of fungus
      Trichoderma harzianum was evaluated through the comparison with the well-known
      biodegradation capability of white-rot fungus Pleurotus ostreatus. The study was
      performed in aqueous phase under aerobic conditions, using two of the most
      frequently detected drugs in water bodies: carbamazepine and clarithromycin, with
      concentrations commonly found in treated wastewater (4MUg/l and 0.03MUg/l
      respectively). For the first time, we demonstrated that T. harzianum is able to
      remove carbamazepine and clarithromycin. The analyses were performed by reversed
      phase liquid chromatography/mass spectrometry, using high-resolution Fourier
      transform ion cyclotron resonance mass spectrometry upon electrospray ionization
      in positive ion mode. The high selectivity and mass accuracy provided by high
      resolution mass spectrometry, allowed us to identify some unknown metabolites. On
      the basis of our study, the major metabolites detected in liquid culture treated
      by T. harzianum were: 14-hydroxy-descladinosyl- and descladinosyl-clarithromycin,
      which are pharmacologically inactive products not dangerous for the environment.

PMID- 27039064
TI  - Comparative environmental impact assessment of herbicides used on genetically
      modified and non-genetically modified herbicide-tolerant canola crops using two
      risk indicators.
AB  - Canola (Brassica napus L.) is the third largest field crop in Australia by area
      sown. Genetically modified (GM) and non-GM canola varieties released or being
      developed in Australia include Clearfield(r) (imidazolinone tolerant), TT
      (triazine tolerant), InVigor(r) (glufosinate-ammonium tolerant), Roundup Ready(r)
      - RR(r) (glyphosate tolerant) and Hyola(r) RT(r) (tolerant to both glyphosate and
      triazine). We used two risk assessment approaches - the Environmental Impact
      Quotient (EIQ) and the Pesticide Impact Rating Index (PIRI) - to compare the
      environmental risks associated with herbicides used in the canola varieties (GM
      and non-GM) that are currently grown or may be grown in the future. Risk
      assessments found that from an environmental impact viewpoint a number of
      herbicides used in the production of TT canola showed high relative risk in terms
      of mobility and ecotoxicity of herbicides. The EIQ field use rating values for
      atrazine and simazine in particular were high compared with those for glyphosate
      and trifluralin. Imazapic and imazapyr, which are only used in Clearfield(r)
      canola, had extremely low EIQ field use rating values, likely reflecting the very
      low application rates used for these chemicals (0.02 to 0.04kg/ha) compared with
      those used for atrazine and simazine (1.2 to 1.5kg/ha). The PIRI assessment
      showed that irrespective of the canola variety grown, trifluralin posed a high
      toxicity risk to fish (Rainbow trout, Oncorhynchus mykiss), algae and Daphnia sp.
      While the replacement of trifluralin with propyzamide had little effect on the
      mobility score, it greatly decreased the ecotoxicity score to fish, algae and
      Daphnia sp. due to the lower LC50 values for propyzamide compared with
      trifluralin. This study has shown that based on likelihood of off-site transport
      of herbicides in surface water and potential toxicity to non-target organisms,
      the GM canola varieties have no advantage over non-herbicide tolerant (non HT) or
      Clearfield(r) canola.

PMID- 27039065
TI  - [Influenza A/H1N1 virus infections associated with bacterial infections
      complicated by extensive compartment syndrome].

PMID- 27039066
TI  - Polymicrobial anaerobic meningitis.

PMID- 27039067
TI  - [Henoch-Schonlein purpura-like vasculitis revealing HIV infection].

PMID- 27039068
TI  - Community-acquired Clostridium difficile infections.
AB  - OBJECTIVE: To describe the management and treatment of community-acquired C.
      difficile infections (CDI) and to evaluate family physicians' (FP) knowledge and
      practice. PATIENTS AND METHODS: Observational study from December 2013 to June
      2014. All community-acquired CDI case patients diagnosed in the community or at
      the University Hospital of Nantes were prospectively included. A questionnaire
      was mailed to 150 FPs of the area of Nantes. RESULTS: A total of 27 community
      acquired CDI case patients were included (incidence: 7.7 case patients/100,000
      inhabitants). Mean age was higher among case patients diagnosed at hospital
      (69years) compared with those diagnosed in the community (44years). Fifteen
      patients were treated at home (55%) and 22 received a first-line treatment with
      metronidazole. Only one patient did not receive any prior antibiotic treatment.
      Amoxicillin-clavulanic acid was mainly prescribed (68%) for respiratory and ENT
      infections (40%). Twenty-three patients were cured on Day 7 and three had
      complications (two deaths). Thirty-one of 47 FPs reported to have already managed
      CDI patients. Twenty-two FPs reported to usually treat patients with
      uncomplicated CDI at home, 21 to refer patients to a specialist, and three to
      hospital. Forty-one FPs reported to prescribe a CD toxin test only after recent
      antibiotic exposure and 30 when patients are at risk of CDI. CONCLUSION: The
      incidence and impact of community-acquired CDIs may be underestimated and the
      unjustified use of antibiotics may promote their emergence. FPs are not used to
      treat CDIs as more than 50% prefer referring patients to hospital or to a
      specialist.

PMID- 27039069
TI  - [Hypoglycemic coma and co-trimoxazole in a nondiabetic patient].

PMID- 27039071
TI  - PAT: predictor for structured units and its application for the optimization of
      target molecules for the generation of synthetic antibodies.
AB  - BACKGROUND: The identification of structured units in a protein sequence is an
      important first step for most biochemical studies. Importantly for this study,
      the identification of stable structured region is a crucial first step to
      generate novel synthetic antibodies. While many approaches to find domains or
      predict structured regions exist, important limitations remain, such as the
      optimization of domain boundaries and the lack of identification of non-domain
      structured units. Moreover, no integrated tool exists to find and optimize
      structural domains within protein sequences. RESULTS: Here, we describe a new
      tool, PAT ( http://www.kimlab.org/software/pat ) that can efficiently identify
      both domains (with optimized boundaries) and non-domain putative structured
      units. PAT automatically analyzes various structural properties, evaluates the
      folding stability, and reports possible structural domains in a given protein
      sequence. For reliability evaluation of PAT, we applied PAT to identify antibody
      target molecules based on the notion that soluble and well-defined protein
      secondary and tertiary structures are appropriate target molecules for synthetic
      antibodies. CONCLUSION: PAT is an efficient and sensitive tool to identify
      structured units. A performance analysis shows that PAT can characterize
      structurally well-defined regions in a given sequence and outperforms other
      efforts to define reliable boundaries of domains. Specially, PAT successfully
      identifies experimentally confirmed target molecules for antibody generation. PAT
      also offers the pre-calculated results of 20,210 human proteins to accelerate
      common queries. PAT can therefore help to investigate large-scale structured
      domains and improve the success rate for synthetic antibody generation.

PMID- 27039070
TI  - BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by
      regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo.
AB  - There has been an increasing recognition that mitochondrial perturbations play a
      central role in human heart failure. Mitochondrial networks, whose function is to
      maintain the regulation of mitochondrial biogenesis, autophagy ('mitophagy') and
      mitochondrial fusion/fission, are new potential therapeutic targets. Yet our
      understanding of the molecular underpinning of these processes is just emerging.
      We recently identified a role of the SWI/SNF ATP-dependent chromatin remodeling
      complexes in the metabolic homeostasis of the adult cardiomyocyte using
      cardiomyocyte-specific and inducible deletion of the SWI/SNF ATPases BRG1 and BRM
      in adult mice (Brg1/Brm double mutant mice). To build upon these observations in
      early altered metabolism, the present study looks at the subsequent alterations
      in mitochondrial quality control mechanisms in the impaired adult cardiomyocyte.
      We identified that Brg1/Brm double-mutant mice exhibited increased mitochondrial
      biogenesis, increases in 'mitophagy', and alterations in mitochondrial fission
      and fusion that led to small, fragmented mitochondria. Mechanistically, increases
      in the autophagy and mitophagy-regulated proteins Beclin1 and Bnip3 were
      identified, paralleling changes seen in human heart failure. Evidence for
      perturbed cardiac mitochondrial dynamics included decreased mitochondria size,
      reduced numbers of mitochondria, and an altered expression of genes regulating
      fusion (Mfn1, Opa1) and fission (Drp1). We also identified cardiac protein
      amyloid accumulation (aggregated fibrils) during disease progression along with
      an increase in pre-amyloid oligomers and an upregulated unfolded protein response
      including increased GRP78, CHOP, and IRE-1 signaling. Together, these findings
      described a role for BRG1 and BRM in mitochondrial quality control, by regulating
      mitochondrial number, mitophagy, and mitochondrial dynamics not previously
      recognized in the adult cardiomyocyte. As critical to the pathogenesis of heart
      failure, epigenetic mechanisms like SWI/SNF chromatin remodeling seem more
      intimately linked to cardiac function and mitochondrial quality control
      mechanisms than previously realized. 

PMID- 27039072
TI  - Rapid chondrolysis of the medial knee compartment after arthroscopic meniscal
      resection: a case report.
AB  - BACKGROUND: Rapidly destructive osteoarthritis of the hip and rapid chondrolysis
      of the lateral compartment of the knee or the shoulder are rare, but have been
      previously described in the medical literature. To the best of our knowledge, no
      case of medial femorotibial compartment chondrolysis after arthroscopy has yet
      been described. We therefore submit the first case report. CASE PRESENTATION: A
      64-year-old white European man presented with right knee pain due to a medial
      meniscal tear with no other abnormality found on examination or imaging. An
      arthroscopic partial medial meniscectomy was performed and early evolution was
      favorable with no signs of infection. He developed knee pain 2 months later. X
      rays showed a thinning of the medial compartment which was confirmed by computed
      tomography arthrogram. There was no articular effusion, mobility was conserved
      (0/0/125 degrees ), there was no laxity, and pain was localized to the medial
      femorotibial compartment, with no meniscal signs. There was a 8 degrees  varus
      deviation (versus 3 degrees  for his uninjured left knee). His blood work was
      normal. As there were no signs of infection, no aspiration was performed.
      Viscosupplementation was offered but refused by the patient. He is now waiting
      for a partial knee replacement. CONCLUSIONS: To the best of our knowledge, this
      is the first description of such a case. Rapid chondrolysis has been described in
      the hip, shoulder, and the lateral compartment of the knee. Infiltration of
      bupivacaine and lateral meniscectomy are the most frequently sited offending
      procedures. Concerning the medial compartment, cases of avascular necrosis have
      been reported after meniscectomy or use of radiofrequency devices. This case
      underlines the necessity of a thorough physical examination and complete
      radiological work up before any surgery. It must also drive us to use caution
      regarding meniscectomy, especially in patients over 60 years of age, and reminds
      us that patients must be informed of this potential complication.

PMID- 27039073
TI  - Quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2
      in vitro and in vivo.
AB  - BACKGROUND: Evidences indicate that inflammatory process plays pivotal role in
      tumor disease. Soluble epoxide hydrolase inhibitors (sEHIs) have been shown to
      participate in anti-inflammation and tumorigenesis by protecting
      epoxyeicosatrienoic acids (EETs). Although we have previously revealed some
      effects of t-AUCB on glioma in vitro, further investigations are needed to
      demonstrate its effects on glioblastoma growth in vivo and how to strengthen its
      antitumor effect. METHODS: CCK-8 kit was used to test cell growth. Cell migration
      capacity was performed by wound healing assays. Transwell assay was used to test
      cell invasion potency. Cell-cycle analysis and cell apoptosis was performed by
      flow cytometry. The activity of caspase-3 in cells was measured using caspase-3
      activity assay kits. Total RNA was extracted from cells lysated by TRIzol
      reagent. qRT-PCR was performed by ABI 7500 fast RT- PCR system. Lipofectamine
      RNAiMAX Transfection Reagent (Invitrogen) was used for siRNA transfection.
      Western blootting was used to test protein expression. Tumor cell xenograft mouse
      models were used for in vivo study. The SPSS version 17.0 software was applied
      for statistical analysis. RESULTS: Our data shown that t-AUCB inhibits cell
      proliferation, migration and invasion and induces cell cycle G1 phase arrest in
      vitro but induces no cell apoptosis; increased Hsp27 activation and following COX
      2 overexpression confer resistance to t-AUCB treatment in glioblastoma both in
      vitro and in vivo; quercetin sensitizes glioblastoma to t-AUCB by dual inhibition
      of Hsp27 and COX-2 in vitro and in vivo. CONCLUSIONS: These results indicate that
      combination of t-AUCB and quercetin may be a potential approach to treating
      glioblastoma.

PMID- 27039074
TI  - Effects of cryopreservation on sperm viability, synthesis of reactive oxygen
      species, and DNA damage of bovine sperm.
AB  - The objective was to examine if there are relationships between alterations in
      sperm viability, reactive oxygen species (ROS) synthesis, and DNA integrity
      induced by cryopreservation of bovine sperm. Four ejaculates were collected from
      each of six bulls. Each ejaculate was diluted and divided into two aliquots; one
      was incubated for 24 hours at 37  degrees C, and the other frozen, thawed, and
      incubated for 24 hours at 37  degrees C. Analyses of quality of sperm were
      performed after 0, 3, 6, 12, and 24 hours of incubation. Progressive motile sperm
      was determined with computer assisted sperm analysis. Percentages of plasma
      membrane- and acrosome-intact sperm, sperm with a high mitochondrial membrane
      potential, sperm showing a high degree of DNA fragmentation (%DFI), and their
      reactive oxygen species content were assessed with dichlorofluorescein-diacetate,
      dihydrorhodamine, diaminofluorescein diacetate, and mitochondrial superoxide
      indicator using flow cytometry. Although all other sperm parameters showed
      alterations (P < 0.05) during the 24-hour incubation time, %DFI stayed constant
      (P > 0.05, 0.91 +/- 0.23) in nonfrozen sperm. Cryopreservation induced changes of
      all sperm parameters (P < 0.05). In contrast to all other sperm parameters,
      dichlorofluorescein-diacetate-fluoroescence indicating the synthesis of H2O2
      showed a similar exponential rise (P < 0.05) like the %DFI values in frozen
      sperm. In conclusion, changes of DNA integrity in frozen sperm seem to be related
      to synthesis of H2O2 but not to sperm viability and synthesis of other reactive
      oxygen species. 

PMID- 27039075
TI  - An investigation of the microbiota in uterine flush samples and endometrial
      biopsies from dairy cows during the first 7 weeks postpartum.
AB  - Metritis and endometritis commonly occur in dairy cows after calving. Although
      numerous studies have been performed to identify the causative pathogens, a
      complete overview has not been done. Metagenomic studies have analyzed the
      bacterial populations of uterine flush samples from postpartum (pp) dairy cows,
      but the microbiota in the uterine luminal fluid may differ from the microbiota of
      the endometrium itself, and important putative pathogens may have been
      overlooked. In the present study, we compared the microbiota of the uterine lumen
      and the endometrium of healthy, metritic, and endometritic cows. Samples were
      collected from 68 Holstein dairy cows at 1, 4, and 7 weeks pp, and the data were
      analyzed by deep sequencing of the V1 and V2 hypervariable regions of the 16S
      ribosomal RNA gene. The results showed that Porphyromonadaceae, Fusobacteriaceae,
      Leptotrichiaceae, and Mycoplasmataceae may be associated with uterine disease.
      The microbiota of the uterine flush samples and the endometrial biopsies were
      correlated, but the microbiota of the biopsies was more diverse. Fusobacteriaceae
      and Leptotrichiaceae were not observed in the biopsies at week 7, whereas they
      accounted for 20% and 13%, respectively, of the bacterial populations in the
      flush samples. The Mycoplasmataceae family was observed in much higher quantity
      in the flush samples than in the biopsies of the endometritis groups at weeks 4
      and 7. Our findings support the observations of previous metagenomic studies and
      illustrate the importance of including endometrial biopsies to obtain more
      detailed knowledge of the pp uterine microbiota. 

PMID- 27039076
TI  - A surgical glove port technique for laparoscopic-assisted ovariohysterectomy for
      pyometra in the bitch.
AB  - The objective of the study was to describe the feasibility of a glove port
      technique for laparoscopic-assisted surgical treatment of canine pyometra. In
      this retrospective case series, a total of 10 female dogs (median age 7 years,
      range 5.5-10.5 years; median weight 37.0 kg, range 12.9-64.0 kg) with pyometra
      were included. A multiaccess port was created from a surgical glove attached to
      an Alexis wound retractor and placed in the ventral midline between the middle
      and caudal third of the distance between umbilicus and pubic rim. A vessel
      sealing device was used for transection of the ovarian pedicle. The port size was
      selected on the basis of maximum uterine diameter determined by ultrasound.
      Median incision length was 5.0 cm (range 3.1-7.7 cm) for a maximum uterine
      diameter of 4.0 cm (range 2.0-7.0 cm). Median surgical time was 57 minutes (range
      48-65 minutes). No case had to be converted to open celiotomy. Complications
      included one case of minor, self-limiting splenic trauma by the endoscope. In
      eight dogs, the distended uterine horns endangered safe access to the ovarian
      pedicle, and the vessel sealing device was inserted through a second cannula
      placed periumbilically. Extension of the original incision was necessary to
      exteriorize organs in two dogs. All dogs recovered quickly and were discharged
      either on the day of surgery or 1 day thereafter. In conclusion, a surgical glove
      port technique in combination with an Alexis wound retractor is feasible for
      surgical laparoscopic treatment of canine pyometra up to a diameter of 7 cm. 

PMID- 27039078
TI  - Progress in the structural and functional characterization of kinetochores.
AB  - Kinetochores are macromolecular complexes built on a specialized chromatin domain
      called the centromere. Kinetochores provide a site of attachment for spindle
      microtubules during mitosis. They also control a cell cycle checkpoint, the
      spindle assembly checkpoint, which coordinates mitotic exit with the completion
      of chromosome alignment on the mitotic spindle. Correct kinetochore operation is
      therefore indispensable for accurate chromosome segregation. With multiple copies
      of at least 30 structural core subunits and a myriad of regulatory subunits,
      kinetochores are among the largest known macromolecular machines. Biochemical
      reconstitution and structural analysis, together with functional studies, are
      bringing to light the organizational principles of these complex and fascinating
      structures. We summarize recent work and identify a few challenges for future
      work. 

PMID- 27039077
TI  - Effectiveness of an intervention in increasing the provision of preventive care
      by community mental health services: a non-randomized, multiple baseline
      implementation trial.
AB  - BACKGROUND: Relative to the general population, people with a mental illness are
      more likely to have modifiable chronic disease health risk behaviours. Care to
      reduce such risks is not routinely provided by community mental health
      clinicians. This study aimed to determine the effectiveness of an intervention in
      increasing the provision of preventive care by such clinicians addressing four
      chronic disease risk behaviours. METHODS: A multiple baseline trial was
      undertaken in two groups of community mental health services in New South Wales,
      Australia (2011-2014). A 12-month practice change intervention was sequentially
      implemented in each group. Outcome data were collected continuously via telephone
      interviews with a random sample of clients over a 3-year period, from 6 months
      pre-intervention in the first group, to 6 months post intervention in the second
      group. Outcomes were client-reported receipt of assessment, advice and referral
      for tobacco smoking, harmful alcohol consumption, inadequate fruit and/or
      vegetable consumption and inadequate physical activity and for the four
      behaviours combined. Logistic regression analyses examined change in client
      reported receipt of care. RESULTS: There was an increase in assessment for all
      risks combined following the intervention (18 to 29 %; OR 3.55, p = 0.002: n =
      805 at baseline, 982 at follow-up). No significant change in assessment, advice
      or referral for each individual risk was found. CONCLUSIONS: The intervention had
      a limited effect on increasing the provision of preventive care. Further research
      is required to determine how to increase the provision of preventive care in
      community mental health services. TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry ACTRN12613000693729.

PMID- 27039079
TI  - Prevalence of metabolic syndrome in Mainland China: a meta-analysis of published
      studies.
AB  - BACKGROUND: Metabolic syndrome (MS) comprises a set of conditions that are risk
      factors for cardiovascular diseases and diabetes. Numerous epidemiological
      studies on MS have been conducted, but there has not been a systematic analysis
      of the prevalence of MS in the Chinese population. Therefore, the aim of this
      study was to estimate the pooled prevalence of MS among subjects in Mainland
      China. METHODS: We performed a systematic review by searching both English and
      Chinese literature databases. Random or fixed effects models were used to
      summarize the prevalence of MS according to statistical tests for heterogeneity.
      Subgroup, sensitivity, and meta-regression analyses were performed to address
      heterogeneity. Publication bias was evaluated using Egger's test. RESULTS: Thirty
      five papers were included in the meta-analysis, with a total population of
      226,653 Chinese subjects. Among subjects aged 15 years and older, the pooled
      prevalence was 24.5% (95% CI: 22.0-26.9%). By sex, the prevalences were 19.2%
      (95% CI: 16.9-21.6%) in males and 27.0% (95% CI: 23.5-30.5%) in females. The
      pooled prevalence of MS increased with age (15-39 years: 13.9%; 40-59 years:
      26.4%; and 60 years: 32.4%). Individuals living in urban areas (24.9%, 95% CI:
      18.5-31.3%) were more likely to suffer from MS than those living in rural areas
      (19.2%, 95% CI: 14.8-23.7%). Hypertension was the most prevalent component of MS
      in males (52.8%), while the most prevalent component of MS for females was
      central obesity (46.1%). CONCLUSIONS: Our systematic review suggested a high
      prevalence of MS among subjects in Mainland China, indicating that MS is a
      serious public health problem. Therefore, more attention should be paid to the
      prevention and control of MS.

PMID- 27039080
TI  - Changes in lipoprotein lipase and endothelial lipase mass in familial
      hypercholesterolemia during three-drug lipid-lowering combination therapy.
AB  - BACKGROUND: This study was performed to compare the effects of three different
      lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein
      lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and
      EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH
      is usually treated by coadministration of these three drugs. METHODS: The pre
      heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored
      at various time points during coadministration of the three drugs from patients
      with heterozygous FH harboring a single mutation in the LDL receptor (n = 16,
      mean age 63 years). The patients were randomly divided into two groups based on
      the timing when ezetimibe was added. RESULTS: Plasma LPL mass concentration was
      significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4
      124.7] to 67.5 [IQR: 62.1-114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10
      mg/day as well as colestimide at 3.62 g/day did not alter its level substantially
      (median = 67.5 [IQR: 62.1-114.3] to 70.2 [IQR: 58.3-106.2], and to 74.9 [IQR:
      55.6-101.3] ng/ml, respectively) in the group starting with rosuvastatin followed
      by the addition of ezetimibe and colestimide. On the other hand, the magnitude in
      LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day
      before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass
      concentration was significantly increased by rosuvastatin at 20 mg/day (median =
      278.8 [IQR: 186.7-288.7] to 297.0 [IQR: 266.2-300.2] ng/ml, P < 0.05), whereas
      other drugs did not significantly alter its level. CONCLUSION: The effects on
      changes of LPL and EL mass differed depending on the lipid-lowering therapy,
      which may impact the prevention of atherosclerosis differently.

PMID- 27039081
TI  - Switching patients with acromegaly from octreotide to pasireotide improves
      biochemical control: crossover extension to a randomized, double-blind, Phase III
      study.
AB  - BACKGROUND: Many patients with acromegaly do not achieve biochemical control with
      first-generation somatostatin analogues. A large, multicenter, randomized, Phase
      III core study demonstrated that pasireotide LAR had significantly superior
      efficacy over octreotide LAR. This analysis explores the efficacy and safety of
      switching therapeutic arms in inadequately controlled patients during a 12-month
      crossover extension. METHODS: Patients with inadequate biochemical control (GH
      >=2.5 MUg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to
      switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days
      (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR
      30 mg/28 days was permitted, but not mandatory, at month 17 or 20. RESULTS:
      Twelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide
      LAR patients achieved GH <2.5 MUg/L and normal IGF-1 (main outcome measure); 27.2
      and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1,
      respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients
      achieved GH <2.5 MUg/L, respectively. Mean (+/-SD) tumor volume further decreased
      from the end of the core study by 25 % (+/-25) and 18 % (+/-28); 54.3 % of
      pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (>=20
      %) tumor volume reduction during the extension. The safety profile of pasireotide
      LAR was similar to that of octreotide LAR, with the exception of the frequency
      and degree of hyperglycemia-related adverse events. CONCLUSIONS: Pasireotide LAR
      is a promising treatment option for patients with acromegaly inadequately
      controlled with the first-generation somatostatin analogue octreotide LAR. TRIAL
      REGISTRATION: clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.

PMID- 27039082
TI  - French Ministry of Health's response to Paris attacks of 13 November 2015.
AB  - On Friday November 13th at 9:20 pm, three kamikaze bombs went off around the
      Stade de France a stadium in Saint-Denis just outside Paris, 4 different
      shootings took place and bombings in Paris and hundreds of people were held
      hostage in a theater.This multi-site terrorist attack was the first of this
      magnitude in France. Drawing the lessons of these attacks and those which
      occurred in other countries from a health perspective is essential to
      continuously adapt and improve the French response to possible future attacks.
      Several issues would need to be further explored: Management of uncertainties:
      When to trigger the plans: after the 1st attack, the 2nd? When do attacks end and
      when to release mobilized resources? Management of victims: How to ensure that
      all victims are secured or taken care of? How to provide assistance when attacks
      are ongoing? Management of teams: Proper follow-up of persons involved in the
      response: health professionals, police and firemen, emergency call centers but
      also civil servants within administration that contributed to the response.
      Communication: Reactivity of all is a key element to secure appropriate resource
      is mobilized for the response. All actors have to be able to communicate quickly
      in a secured way.

PMID- 27039083
TI  - Workload, mental health and burnout indicators among female physicians.
AB  - BACKGROUND: Female doctors in Hungary have worse indicators of physical and
      mental health compared with other professional women. We aimed to cast light on
      possible indicators of mental health, workload, and burnout of female physicians.
      METHODS: Two time-points (T) were compared, in 2003 (T1 n = 408) and 2013 (T2 n =
      2414), based on two nationally representative surveys of female doctors, and
      comparison made with data from other professional control groups. Independent
      samples t test or chi-squared test was used both for the two time-point
      comparison and the comparison between the index and the control groups. The
      background factors of sleep disorders and burnout were assessed by binary
      logistic regression analysis. RESULTS: No significant differences in the rates of
      depressive symptoms and suicidal thoughts and attempts were detected between the
      2003 and 2013 cohorts, but the prevalence of sleep disorders increased. The
      workload increased, and there was less job satisfaction in 2013 than in 2003,
      coupled to more stressful or difficult work-related situations. The personal
      accomplishment component of burnout significantly decreased in line with the
      declining work-related satisfaction. Compared to the professional control groups,
      the prevalence of depressive symptoms, suicide attempts, and sleep disorders was
      higher among female physicians at both time-points. The number of workplaces,
      frequency of work-related stressful situations, and intensive role conflict was
      associated with sleep disorders and decreased personal accomplishment.
      CONCLUSIONS: In comparison with the other professional groups, female doctors had
      worse mental health indicators with regard to depression, suicidal ideas, and
      sleep disorders both in 2003 and 2013 while within professional strata the
      changes seemed to be less. Increasing workload had a clear impact on sleep
      disorders and the personal accomplishment dimension of burnout.

PMID- 27039084
TI  - The effects of ivabradine on left atrial electromechanical function in patients
      with systolic heart failure.
AB  - AIM: Heart rate (HR) reduction with ivabradine improves left ventricle filling by
      the prolongation of the diastolic time and increases stroke volume. But, it
      remains unclear what ivabradine's effect is on atrial conduction time and atrial
      mechanical functions. The aim of our study was to evaluate in stable outpatients
      with systolic heart failure (HF) the 3 months effect of ivabradine on atrial
      conduction time and mechanical functions. METHOD: We evaluated prospectively 43
      (31 males, 12 females) patients with HF. Before and after treatment, all patients
      were evaluated by transthoracic M mode, two dimensional (2D), pulsed-wave (PW),
      continuous wave (CW), color flow and tissue Doppler imaging (TDI), and LA volumes
      were obtained apical four-chamber views by a disc's method. LA maximum volume
      (Vmax) at the end-systolic phase, LA minimum volume (Vmin) at the end-diastolic
      phase, and LA volume before atrial systole (Vp) were evaluated. The LA function
      parameters were calculated as follows: LA passive emptying volume = Vmax - Vp; LA
      passive emptying fraction = [(Vmax - Vp)/Vmax] * 100%, LA active emptying volume
      = Vp - Vmin; LA active emptying fraction = [(Vp - Vmin)/Vp] * 100%. RESULTS:
      Thirty men and 13 women with mean +/- SD age of 63.9 +/- 10.1 years were included
      in this study. Resting heart rate was significantly reduced after ivabradine
      treatment. There were no significantly difference in LVEF, and E/A before and
      after ivabradine treatment. LA diameter and Vmin were similar before and after
      ivabradine treatment (p = 0.793 and p = 0.284). However, Vmax and Vp were
      significantly decreased after ivabradine treatment (p = 0.040 and p = 0.012).
      Moreover, LA active emptying volume and LA active emptying fraction were
      significantly decreased after ivabradine treatment (p = 0.030 and p = 0.008). The
      PA lateral, septal, and tricuspid durations were significantly reduced after
      ivabradine treatment (p < 0.001, p < 0.001, and p = 0.002, respectively).
      Interatrial electromechanical delay and right intra-atrial electromechanical
      delay were significantly decreased after ivabradine treatment (33.7 +/- 12.7 vs
      26.2 +/- 10.1, p = 0.001; and 14.1 +/- 6.1 vs 9.2 +/- 6.8, p < 0.001).
      CONCLUSIONS: The present study demonstrated that adding ivabradine to the
      standard therapy reduced HR and improves significantly LA electrical and
      mechanical functions in systolic HF patients.

PMID- 27039085
TI  - Interaction of plant growth regulators and reactive oxygen species to regulate
      petal senescence in wallflowers (Erysimum linifolium).
AB  - BACKGROUND: In many species floral senescence is coordinated by ethylene.
      Endogenous levels rise, and exogenous application accelerates senescence.
      Furthermore, floral senescence is often associated with increased reactive oxygen
      species, and is delayed by exogenously applied cytokinin. However, how these
      processes are linked remains largely unresolved. Erysimum linifolium (wallflower)
      provides an excellent model for understanding these interactions due to its
      easily staged flowers and close taxonomic relationship to Arabidopsis. This has
      facilitated microarray analysis of gene expression during petal senescence and
      provided gene markers for following the effects of treatments on different
      regulatory pathways. RESULTS: In detached Erysimum linifolium (wallflower)
      flowers ethylene production peaks in open flowers. Furthermore senescence is
      delayed by treatments with the ethylene signalling inhibitor silver thiosulphate,
      and accelerated with ethylene released by 2-chloroethylphosphonic acid. Both
      treatments with exogenous cytokinin, or 6-methyl purine (which is an inhibitor of
      cytokinin oxidase), delay petal senescence. However, treatment with cytokinin
      also increases ethylene biosynthesis. Despite the similar effects on senescence,
      transcript abundance of gene markers is affected differentially by the
      treatments. A significant rise in transcript abundance of WLS73 (a putative
      aminocyclopropanecarboxylate oxidase) was abolished by cytokinin or 6-methyl
      purine treatments. In contrast, WFSAG12 transcript (a senescence marker)
      continued to accumulate significantly, albeit at a reduced rate. Silver
      thiosulphate suppressed the increase in transcript abundance both of WFSAG12 and
      WLS73. Activity of reactive oxygen species scavenging enzymes changed during
      senescence. Treatments that increased cytokinin levels, or inhibited ethylene
      action, reduced accumulation of hydrogen peroxide. Furthermore, although auxin
      levels rose with senescence, treatments that delayed early senescence did not
      affect transcript abundance of WPS46, an auxin-induced gene. CONCLUSIONS: A model
      for the interaction between cytokinins, ethylene, reactive oxygen species and
      auxin in the regulation of floral senescence in wallflowers is proposed. The
      combined increase in ethylene and reduction in cytokinin triggers the initiation
      of senescence and these two plant growth regulators directly or indirectly result
      in increased reactive oxygen species levels. A fall in conjugated auxin and/or
      the total auxin pool eventually triggers abscission.

PMID- 27039087
TI  - Erratum to: Molecular detection and identification of piroplasms in sika deer
      (Cervus nippon) from Jilin Province, China.

PMID- 27039086
TI  - Effect of acupuncture and its influence on cerebral activity in functional
      dyspepsia patients: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Functional dyspepsia (FD) is a prevalent gastric disorder that is
      difficult to manage due to lack of satisfactory treatments. Acupuncture has been
      studied with regard to the rising need for treating FD, but the mechanism
      verifying its efficacy has not yet been fully revealed. The aim of this study is
      to explore the efficacy and mechanism of acupuncture for FD compared with a sham
      group. METHODS/DESIGN: We describe a proposal for a randomized, assessor-blind,
      sham-controlled trial with 70 eligible participants who will be randomly
      allocated either into an acupuncture or a sham group. Participants in the
      acupuncture group will receive 10 sessions of real acupuncture treatment and
      those in the sham group will be treated with identical sessions using a
      Streitberger needle. Functional magnetic resonance imaging (fMRI) and
      metabolomics studies will be implemented before and after 4 weeks of treatment to
      investigate the mechanism of acupuncture. The primary outcome is a proportion of
      responders with adequate symptom relief and the secondary outcomes include the
      Nepean Dyspepsia Index - Korean version, Functional Dyspepsia-Related Quality of
      Life questionnaire, Ways of Coping Questionnaire, Coping Strategies
      Questionnaire, perception of bodily sensation questionnaire, State-Trait Anxiety
      Inventory, and the Center for Epidemiological Studies - Depression Scale. The
      outcomes will be evaluated before and after the treatment. DISCUSSION: This is
      the first large-scale trial evaluating the efficacy and mechanism of acupuncture
      with fMRI and metabolomic methods. We will compare real acupuncture with the
      Streitberger sham needle to verify the specific effect of acupuncture. The
      results of this trial are expected to be relevant evidences affecting policy and
      decision-makers associated with routine healthcare. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02358486 . Date of Registration: 21 January
      2015.

PMID- 27039088
TI  - Naive-pooled pharmacokinetic analysis of pyrazinamide, isoniazid and rifampicin
      in plasma and cerebrospinal fluid of Vietnamese children with tuberculous
      meningitis.
AB  - BACKGROUND: Among the various forms of TB, tuberculous meningitis (TBM) is the
      most severe, with about 30% mortality and 50% of survivors left with neurological
      sequelae. Children suffer more frequently from TBM than adults and outcomes are
      often poor due to difficulties in making the diagnosis and uncertainty regarding
      the best anti-tuberculosis drug regimen. The aim of this prospective study was to
      describe the pharmacokinetics of pyrazinamide, isoniazid and rifampicin in plasma
      and cerebrospinal fluid of children with tuberculous meningitis treated with the
      standard TBM regimen. METHODS: We performed a prospective observational study of
      100 consecutively treated children (<= 15 years of age) with tuberculous
      meningitis in Ho Chi Minh City, Vietnam. Children were treated according to the
      2006 WHO recommended pediatric treatment regimen consisting of isoniazid (5
      mg/kg), rifampicin (10 mg/kg) and ethambutol (15 mg/kg) for 8 months, with the
      addition of pyrazinamide (25 mg/kg) for the first 3 months and streptomycin (15
      mg/kg) for the first 2 months. Pyrazinamide, isoniazid and rifampicin
      concentrations were measured in plasma at day 14 and in cerebrospinal fluid (CSF)
      at 1 month by HPLC-UV. A naive-pooled non-compartmental data analysis was used to
      describe the pharmacokinetic properties of drugs in the two-age groups of
      children <= 4 years or > 4 years of age. RESULTS: Younger children, when compared
      to older children, presented a higher body weight-normalized clearance and volume
      of distribution, and lower median total plasma exposures for the three studied
      drugs with -14%, -22% and -16% for Pyrazinamide, Isoniazid and Rifampicin,
      respectively. In CSF, individual concentrations of isoniazid and pyrazinamide
      were comparable to that in plasma in both age groups; but rifampicin
      concentrations were lower than the minimum inhibitory concentration of
      susceptible bacteria in all but two children. CONCLUSIONS: There is an age
      dependent variation in the plasma and cerebrospinal fluid pharmacokinetics of
      rifampicin, isoniazid and pyrazinamide. The safety and efficacy of higher doses
      of rifampicin should be investigated for the treatment of childhood tuberculous
      meningitis.

PMID- 27039089
TI  - beta-Glucan exacerbates allergic airway responses to house dust mite allergen.
AB  - beta-(1,3)-Glucan is present in mould cell walls and frequently detected in house
      dust mite (HDM) faeces. beta-Glucan exposure is thought to be associated with
      pulmonary allergic inflammation in mouse and man, although the published data are
      inconsistent. Here, we show that highly purified beta-glucan exacerbates HDM
      induced eosinophilic, T helper 2 type airway responses by acting as an adjuvant,
      promoting activation, proliferation and polarisation of HDM-specific T cells (1
      Derbeta T cells). We therefore provide definitive evidence that beta-glucan can
      influence allergic pulmonary inflammation. 

PMID- 27039090
TI  - Medication at discharge in an orthopaedic surgical ward: quality of information
      transmission and implementation of a medication reconciliation form.
AB  - Background Medication reconciliation (MedRec) at discharge is a cumbersome but
      necessary process to reduce the risk of medication errors at transitions of care.
      The main barriers to implementing such a process are the large number of
      professionals involved and a lack of collaboration among caregivers. Objective
      This study was designed to assess the need for a medication reconciliation form
      at discharge in an orthopaedic surgical ward. Setting The study was conducted in
      the orthopaedic surgery ward among inpatients at a 407-bed French teaching
      hospital. Method We first performed a retrospective audit to evaluate the quality
      of discharge medication information in the medical record, after which a 5-week
      prospective study was conducted in 2013. All patients admitted to the orthopaedic
      surgery unit who had at least two chronic diseases and three medications
      underwent MedRec at discharge. We designed a Best Possible Medication at
      Discharge List (BPMDL) to be completed by hospital staff and transmitted to
      community caregivers. Mean outcome measures We assessed the completeness of
      medication information in the medical records, discrepancies between medications
      noted on the BPMDL and those prescribed on the discharge order, and the value of
      the BPMDL for stakeholders. Results Thirty patients were included in the study.
      Only 4 % of medical records contained a discharge summary with complete
      medication information. In 67 % of cases, treatment discontinuations at admission
      were justified, and medications were reintroduced before discharge, while 107
      treatments (45 %) were added but not prescribed on discharge orders.
      Discontinuations prior to discharge were justified in 60 % of cases (treatments
      were ended or supportive treatment was required during hospitalization). An
      average of 2.1 treatments were prescribed on discharge orders (vs. 9.4 prescribed
      on the BPMDL). Patients, general practitioners (GP), and physicians in long-term
      care settings (PLTCS) rated the format, content, and readability of the BPMDL as
      satisfactory, and it was found to be of value for patients and PLTCS to support
      medication information. Because of the very low response rate among GP (10 %), we
      were unable to determine their satisfaction with the MedRec discharge process.
      Conclusion The transmission of patient medication information at discharge is
      often lacking. As such, the BPMDL appears to have value to both patients and
      community health providers. Because this study was conducted within a single
      surgical unit, further study in other surgical wards is needed to assess
      generalizability. 

PMID- 27039091
TI  - The challenges of outcome research.
AB  - Cognitive pharmacy trials seek to identify interventions that benefit patients.
      The potential benefits of an intervention are primarily evaluated by outcome
      measures. The question then is: What is the optimal outcome measure?
      Unfortunately, the question remains unsolved. Several factors must be taken into
      consideration when conducting outcome research-particularly within cognitive
      pharmacy trials. The interventions are often complex and non-specific, and seek
      to improve symptom control, optimise the use of medications and reduce medication
      related risks. "Hard" endpoints, such as mortality and hospital admissions, may
      not be the optimal outcome measures, since cognitive pharmacy interventions are
      unlikely to result in changes in these measures. Instead, adverse drug events or
      "soft" endpoints, such as quality of life, drug-related problems and patient
      satisfaction may be appropriate choices of outcome measures. Finally, it is not
      only outcome measures that may pose a challenge when conducting outcome research;
      other essential components include study design, type of intervention, the
      patient population, etc. 

PMID- 27039092
TI  - Creating More Effective Mentors: Mentoring the Mentor.
AB  - Given the diversity of those affected by HIV, increasing diversity in the HIV
      biomedical research workforce is imperative. A growing body of empirical and
      experimental evidence supports the importance of strong mentorship in the
      development and success of trainees and early career investigators in academic
      research settings, especially for mentees of diversity. Often missing from this
      discussion is the need for robust mentoring training programs to ensure that
      mentors are trained in best practices on the tools and techniques of mentoring.
      Recent experimental evidence shows improvement in mentor and mentee perceptions
      of mentor competency after structured and formalized training on best practices
      in mentoring. We developed a 2-day "Mentoring the Mentors" workshop at UCSF to
      train mid-level and senior HIV researchers from around the country [recruited
      mainly from Centers for AIDS Research (CFARs)] on best practices, tools and
      techniques of effective mentoring. The workshop content was designed using
      principles of Social Cognitive Career Theory (SCCT) and included training
      specifically geared towards working with early career investigators from
      underrepresented groups, including sessions on unconscious bias,
      microaggressions, and diversity supplements. The workshop has been held three
      times (September 2012, October 2013 and May 2015) with plans for annual training.
      Mentoring competency was measured using a validated tool before and after each
      workshop. Mentoring competency skills in six domains of mentoring-specifically
      effective communication, aligning expectations, assessing understanding,
      fostering independence, addressing diversity and promoting development-all
      improved as assessed by a validated measurement tool for participants pre- and 
      post the "Mentoring the Mentors" training workshops. Qualitative assessments
      indicated a greater awareness of the micro-insults and unconscious bias
      experienced by mentees of diversity and a commitment to improve awareness and
      mitigate these effects via the mentor-mentee relationship. Our "Mentoring the
      Mentors" workshop for HIV researchers/mentors offers a formal and structured
      curriculum on best practices, tools and techniques of effective mentoring, and
      methods to mitigate unconscious bias in the mentoring relationship. We found
      quantitative and qualitative improvements in mentoring skills as assessed by self
      report by participants after each workshop and plan additional programs with
      longitudinal longer-term assessments focused on objective mentee outcomes
      (grants, papers, academic retention). Mentoring training can improve mentoring
      skills and is likely to improve outcomes for optimally-mentored mentees.

PMID- 27039093
TI  - A specific dose of grape seed-derived proanthocyanidins to inhibit body weight
      gain limits food intake and increases energy expenditure in rats.
AB  - PURPOSE: Several studies have suggested that flavanols may have antiobesity
      effects; however, those effects clearly depend on the experimental conditions. In
      a previous study, we found that a single acute dose of grape seed
      proanthocyanidin extract (GSPE) has satiating effects. We therefore hypothesise
      that satiating doses of GSPE could be used to reduce body weight gain, and our
      present objective was to define the most effective dose. METHODS: We assayed two
      GSPE doses in aged male Wistar rats. First we performed a subchronic (8-day)
      treatment by intragastric administration, which was repeated after a washout
      period. We measured body weight, energy intake and faeces composition; we
      performed indirect calorimetry; and we analysed the mRNA expression of genes
      involved in lipid metabolism to determine the target tissue for the GSPE.
      RESULTS: We observed that 0.5 g GSPE/kg BW significantly reduced food intake and
      thus the amount of energy absorbed. This dosage also increased lipid oxidation in
      subcutaneous adipose tissue, thus causing a higher total energy expenditure.
      These combined effects caused a decrease in body weight. Conversely, 1 g GSPE/kg
      BW, which also reduced energy absorption after the first treatment, had a rebound
      effect on body weight gain which resulted in a lower response to the
      proanthocyanidin extract. That is, after the second treatment, the GSPE did not
      reduce the energy absorbed or modify energy expenditure and body weight.
      CONCLUSION: GSPE at a dose of 0.5 g/kg can reduce body weight by limiting food
      intake and activating energy expenditure in subcutaneous adipose tissue.

PMID- 27039094
TI  - Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor
      Formation, but Induces Pathological Lobulation of the Developing Cerebellum.
AB  - LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene
      expression during development and carcinogenesis. It is strongly upregulated in a
      variety of brain tumors, such as medulloblastoma, embryonal tumor with
      multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or
      glioblastoma, but the effect of an in vivo overexpression of LIN28B on the
      developing central nervous system is unknown. We generated transgenic mice that
      either overexpressed Lin28b in Math1-positive cerebellar granule neuron
      precursors or in a broad range of Nestin-positive neural precursors. Sections of
      the cerebellar vermis from adult Math1-Cre::lsl-Lin28b mice had an additional
      subfissure in lobule IV. Vermes from p0 and p7 Nestin-Cre::lsl-Lin28b mice
      appeared normal, but we found a pronounced vermal hypersublobulation at p15 and
      p21 in these mice. Also, the external granule cell layer (EGL) was thicker at p15
      than in controls, contained more proliferating cells, and persisted up to p21.
      Consistently, some Pax6- and NeuN-positive cells were present in the EGL of
      Nestin-Cre::lsl-Lin28b mice even at p21, and we detected more NeuN-positive
      granule neuron precursors in the molecular layer (ML) as compared to control.
      Finally, we found some residual Pax2-positive precursors of inhibitory
      interneurons in the ML of Nestin-Cre::lsl-Lin28b mice at p21, which have already
      disappeared in controls. We conclude that while overexpression of LIN28B in
      Nestin-positive cells does not lead to tumor formation, it results in a
      protracted development of granule cells and inhibitory interneurons and leads to
      a hypersublobulation of the cerebellar vermis.

PMID- 27039096
TI  - Modified barbed soft palatal posterior pillar webbing flap palatopharyngoplasty.
AB  - BACKGROUND: The soft palate and the lateral pharyngeal walls contribute to the
      collapse of the upper airway in patients with snoring and obstructive sleep
      apnea. In this study, the original soft palatal webbing flap palatopharyngoplasty
      for both soft palatal and oropharyngeal lateral wall collapse has been modified
      to include all tonsil grades and to apply the barbed suture technique. METHODS:
      Twenty-one adults with significant soft palatal webbing, lateral pharyngeal wall
      collapse, and tonsil hypertrophy of any grade were selected for the study with a
      minimum follow-up period of 6 months. RESULTS: Snoring was improved with snoring
      scale reduced from 9.4 +/- 1.6 to 1.7 +/- 3.2 (p < 0.005). The preoperative to
      postoperative apnea-hypopnea index (AHI) statistically improved from 45.7 +/- 2.6
      to 12.3 +/- 3.9 (p < 0.005) and lowest O2 saturation from 73.8 +/- 3.6 to 89.4 +/
      1.9 % (p < 0.005). Postoperative endoscopic findings showed significant
      improvement in soft palatal and lateral pharyngeal wall collapse. There were no
      significant intraoperative or postoperative complications. CONCLUSION: Modified
      barbed soft palatal webbing flap palatopharyngoplasty provided objective
      improvement of obstructive sleep apnea (OSA) in adults with soft palatal, lateral
      pharyngeal wall collapse and tonsillar hypertrophy, with no significant
      complications and has the potential to serve as an effective alternative for
      these cases.

PMID- 27039095
TI  - Inhibition of Ectodermal-Neural Cortex 1 Protects Neural Cells from Apoptosis
      Induced by Hypoxia and Hypoglycemia.
AB  - Ectodermal-neural cortex 1 (Enc1), a member of the KELCH family, is widely
      expressed in the nervous system and plays an important role in nervous system
      development. However, the function of Enc1 in neural survival following apoptosis
      induced by hypoxia and hypoglycemia remains unclear. In this study, we aimed to
      investigate the role of Enc1 in the cell survival of neurons subjected to
      apoptosis induced by oxygen-glucose deprivation (OGD) and the potential
      underlying mechanism. The in vitro cell model of neuron OGD was established by
      anoxia/hypoglycemic injury. Real-time quantitative PCR and Western blot analyses
      showed that Enc1 was significantly reduced in neurons under anoxia/hypoglycemic
      injury. Knockdown of Enc1 by small interfering RNA markedly promoted the survival
      of neurons under anoxia/hypoglycemia. Moreover, knockdown of Enc1 inhibited
      neuronal apoptosis. Conversely, overexpression of Enc1 showed the opposite
      effect. Further, data demonstrated that Enc1 might regulate neuron survival
      through heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor
      (Nrf2). Taken together, our study suggests that knockdown of Enc1 protects
      newborn neurons from apoptosis induced by OGD associated with Nrf2 and HO-1,
      providing a novel molecular target for the treatment of neonatal apoptosis
      induced by hypoxia and hypoglycemia brain injury. 

PMID- 27039097
TI  - Scaling exponent values as an ordinary function of the ratio of very low
      frequency to high frequency powers in heart rate variability over various sleep
      stages.
AB  - PURPOSE: To assess the physiological meanings of the detrended fluctuation
      analysis (DFA) slope alpha and its relationship to spectral measures in heart
      rate variability, this study investigated changes of alpha and its corresponding
      spectral measures over various night-sleep stages. METHODS: The overall DFA alpha
      and natural-logarithm-transformed power values of the spectral parameters ln[high
      frequency (HF)], ln[low-frequency (LF)], and ln[very-low-frequency (VLF)], and
      their relationship from one 5-min proper electrocardiography segment in each of
      pre-sleep-wakefulness (AWK), non-rapid eye movement stage 2 (N2), slow-wave (N3),
      the first and the latest rapid-eye movement sleep (REM1, and REM2), were computed
      in 93 otherwise healthy males (44.1 +/- 7.7 years.) with wide-ranged apnea
      hypopnea, periodic-limb movement and arousal indices (19.0 +/- 20.9, 4.7 +/- 9.9,
      and 10.7 +/- 18.2 h, respectively). RESULTS: While ln(HF) dipped from AWK, N2,
      and N3 to REM1 then rebounded to the origin level at REM2, ln(VLF) dipped from
      AWK to N2, N3 trough, and then surged to levels surpassing AWKs and N2s at REM1
      and REM2. ln(LF/HF), ln(VLF/HF), and alpha dipped from AWK and N2 to N3 trough,
      surged to levels surpassing AWKs, and N2s at REM1 then became attenuated at REM2.
      By general linear modeling, the relationship between alpha and the corresponding
      spectral values can be seen over various stages as alpha = b 0 + 0.147 *
      ln(VLF/HF) (R (2) = 0.766), regardless of age and sleep-sympathoexcitatory
      episodes. CONCLUSION: The REM sleep attenuations appeared in ln(HF) and its
      derivatives, such as ln(LF/HF), ln(VLF/HF), and the overall DFA slope alpha
      values. The quantitative function of ln(VLF/HF) describes the alpha values
      constantly for overnight sleep stages, and it is not affected by age, LF, PLM,
      and AHI. Our findings therefore suggest that in sleep studies with spectral HRV
      measures, ln(VLF/HF) as a surrogate of the overall DFA slope alpha should be
      calculated at the same time.

PMID- 27039098
TI  - Modelling the healthcare costs of skin cancer in South Africa.
AB  - BACKGROUND: Skin cancer is a growing public health problem in South Africa due to
      its high ambient ultraviolet radiation environment. The purpose of this study was
      to estimate the annual health system costs of cutaneous melanoma, squamous cell
      carcinoma (SCC) and basal cell carcinoma (BCC) in South Africa, incorporating
      both the public and private sectors. METHODS: A cost-of-illness study was used to
      measure the economic burden of skin cancer and a 'bottom-up' micro-costing
      approach. Clinicians provided data on the patterns of care and treatments while
      national costing reports and clinician fees provided cost estimates. The mean
      costs per melanoma and per SCC/BCC were extrapolated to estimate national costs
      using published incidence data and official population statistics. One-way and
      probabilistic sensitivity analyses were undertaken to address the uncertainty of
      the parameters used in the model. RESULTS: The estimated total annual cost of
      treating skin cancers in South Africa were ZAR 92.4 million (2015) (or US$15.7
      million). Sensitivity analyses showed that the total costs could vary between ZAR
      89.7 to 94.6 million (US$15.2 to $16.1 million) when melanoma-related variables
      were changed and between ZAR 78.4 to 113.5 million ($13.3 to $19.3 million) when
      non-melanoma-related variables were changed. The primary drivers of overall costs
      were the cost of excisions, follow-up care, radical lymph node dissection,
      cryotherapy and radiation therapy. CONCLUSION: The cost of managing skin cancer
      in South Africa is sizable. Since skin cancer is largely preventable through
      improvements to sun-protection awareness and skin cancer prevention programs,
      this study highlights these healthcare resources could be used for other pressing
      public health problems in South Africa.

PMID- 27039099
TI  - Social Well-Being Among Colombian and Peruvian Immigrants in Northern Chile.
AB  - In recent years, northern Chile has received a large number of immigrants
      attracted mainly by mining and related services. The last population census
      revealed that 70.5 % of foreigners in Chile came from South America, and were
      mainly Peruvians (30.5 %), Argentines (16.8 %), and Colombians (8.1 %). The aim
      of this cross-sectional study is to describe the social well-being levels
      reported by Colombian and Peruvian immigrants in northern Chile, as well as their
      connection to socio-demographic and relational factors. The Spanish version of
      the Scale of Social Well-being (Keyes in Soc Psychol Q 61:121-140, 1998) was
      administered to 431 men and women over 18 years old, with a minimum residence of
      6 months in the city of Antofagasta. The highest-rated aspect was Social
      Contribution, and the lowest-rated aspect was Social Acceptance. The relational
      variables that show statistically significant differences in both populations
      relate to who the subject lives with, the degree of contact that the subject has
      with people from Chile, and the subject's relationship status. There are no
      differences that indicate a higher level of social well-being in one population
      more than the other; however, it appears that the Peruvian population has a
      greater perception of Social Coherence, while Colombians show a greater
      perception of Social Contribution.

PMID- 27039100
TI  - Associations Between Discrimination and Cardiovascular Health Among Asian Indians
      in the United States.
AB  - Asian Indians (AI) have a high risk of atherosclerotic cardiovascular disease.
      The study investigated associations between discrimination and (1) cardiovascular
      risk and (2) self-rated health among AI. Higher discrimination scores were
      hypothesized to relate to a higher cardiovascular risk score (CRS) and poorer
      self-rated health. Asian Indians (n = 757) recruited between 2010 and 2013
      answered discrimination and self-reported health questions. The CRS (0-8 points)
      included body-mass index, systolic blood pressure, total cholesterol, and fasting
      blood glucose levels of AI. Multiple linear regression analyses were conducted to
      evaluate relationships between discrimination and the CRS and discrimination and
      self-rated health, adjusting for psychosocial and clinical factors. There were no
      significant relationships between discrimination and the CRS (p >= .05).
      Discrimination was related to poorer self-reported health, B = -.41 (SE = .17), p
      = .02. Findings suggest perhaps there are important levels at which
      discrimination may harm health.

PMID- 27039101
TI  - Usefulness of Baltasar's expected body mass index as an indicator of bariatric
      weight loss surgery.
AB  - INTRODUCTION: Determining the best indicator to report weight loss takes on
      special relevance following bariatric surgery. Our objective is to apply a method
      proposed by Baltasar et al. to express weight loss results following bariatric
      surgery. MATERIALS AND METHODS: Anthropometric data were collected from 265
      patients who had undergone Sleeve gastrectomy (SG, n = 172) and Roux-en-Y gastric
      bypass (RYGBP, n = 93) with a 2-year follow-up period. Initial BMI was calculated
      as well as BMI 2 years after, percentage of excess BMI loss (PEBMIL), expected
      BMI (EBMI), and corrected PEBMIL. RESULTS: In SG group, average BMI 2 years after
      surgery fell within a 95 % CI of expected BMI, with an average BMI of 31.58 +/-
      4.05 kg/m2 in 35-45 BMI group, an average BMI of 33.62 +/- 4.96 kg/m2 in 45-55
      BMI group, and an average BMI of 37.40 +/- 5.93 kg/m2 in 55-65 BMI group. In
      RYGBP group, average BMI 2 years after the surgery was below than average
      expected BMI (28.76 +/- 3.20 kg/m2 in 35-45 BMI group and 29.71 +/- 3.30 kg/m2 in
      45-55 BMI group). Results are considered excellent for the group with an initial
      BMI of above 45 kg/m2. CONCLUSIONS: EBMI is a good weight loss indicator, mainly
      when 95 % CI is taken into account. EBMI is consistent with the results obtained
      2 years after surgery in our patients who underwent SG and RYGBP. Corrected
      PEBMIL is a good indicator for expressing the percentage of BMI loss and offers
      more realistic values than conventional formula with a cut-off point of 25
      points.

PMID- 27039102
TI  - Iron-Deficiency Anemia After Laparoscopic Roux-en-Y Gastric Bypass in Chinese
      Obese Patients with Type 2 Diabetes: a 2-Year Follow-Up Study.
AB  - BACKGROUND: This study was conducted to evaluate the prevalence of iron
      deficiency anemia (IDA) after Roux-en-Y gastric bypass (RYGB) in Chinese obese
      patients with type 2 diabetes (T2DM). Furthermore, we evaluate potential
      predicting factors for onset of IDA after RYGB. METHODS: A total of 184 obese
      T2DM individuals who underwent RYGB were enrolled in the study. Patients were
      divided into three groups: male, premenopausal female, and postmenopausal female.
      Hematologic parameters were obtained prior to and after surgery on standardized
      time intervals up to 24 months postoperatively. RESULTS: At baseline, 6.0 % of
      patients were anemic, with similar percentages of anemic patients in each group.
      The relative decrease in the mean hemoglobin (Hb) level was significantly more
      pronounced for premenopausal female than for postmenopausal female or male. The
      percentage of anemia in male group had increased to 15.2 and 17.0 % at 6 and 12
      months, respectively, and then decreased to 4.5 % at 24-month visit. In
      postmenopausal female group, the percentages of anemia constantly increase to
      34.0 % at 6-month follow-up. Then, it decreased gradually to 25.0 and 26.7 % at
      12- and 24-month visits, respectively. In premenopausal female group, the anemia
      percentages dramatically increased to 62.5 % at 24-month follow-up. Multiple
      logistic regression indicated that lower serum ferritin level preoperative and
      female were associated with higher possibility to suffer IDA 2 years after RYGB.
      CONCLUSIONS: Iron-deficiency and IDA are extremely frequent after RYGB in Chinese
      obese patients with T2DM. Premenopausal female presents unexpectedly high
      incidence of IDA during the 2-year observation.

PMID- 27039104
TI  - Mechanistic evaluation of primary human hepatocyte culture using global proteomic
      analysis reveals a selective dedifferentiation profile.
AB  - The application of primary human hepatocytes following isolation from human
      tissue is well accepted to be compromised by the process of dedifferentiation.
      This phenomenon reduces many unique hepatocyte functions, limiting their use in
      drug disposition and toxicity assessment. The aetiology of dedifferentiation has
      not been well defined, and further understanding of the process would allow the
      development of novel strategies for sustaining the hepatocyte phenotype in
      culture or for improving protocols for maturation of hepatocytes generated from
      stem cells. We have therefore carried out the first proteomic comparison of
      primary human hepatocyte differentiation. Cells were cultured for 0, 24, 72 and
      168 h as a monolayer in order to permit unrestricted hepatocyte
      dedifferentiation, so as to reveal the causative signalling pathways and factors
      in this process, by pathway analysis. A total of 3430 proteins were identified
      with a false detection rate of <1 %, of which 1117 were quantified at every time
      point. Increasing numbers of significantly differentially expressed proteins
      compared with the freshly isolated cells were observed at 24 h (40 proteins), 72
      h (118 proteins) and 168 h (272 proteins) (p < 0.05). In particular, cytochromes
      P450 and mitochondrial proteins underwent major changes, confirmed by functional
      studies and investigated by pathway analysis. We report the key factors and
      pathways which underlie the loss of hepatic phenotype in vitro, particularly
      those driving the large-scale and selective remodelling of the mitochondrial and
      metabolic proteomes. In summary, these findings expand the current understanding
      of dedifferentiation should facilitate further development of simple and complex
      hepatic culture systems.

PMID- 27039105
TI  - Metabolomic network analysis of estrogen-stimulated MCF-7 cells: a comparison of
      overrepresentation analysis, quantitative enrichment analysis and pathway
      analysis versus metabolite network analysis.
AB  - In the context of the Human Toxome project, mass spectroscopy-based metabolomics
      characterization of estrogen-stimulated MCF-7 cells was studied in order to
      support the untargeted deduction of pathways of toxicity. A targeted and
      untargeted approach using overrepresentation analysis (ORA), quantitative
      enrichment analysis (QEA) and pathway analysis (PA) and a metabolite network
      approach were compared. Any untargeted approach necessarily has some noise in the
      data owing to artifacts, outliers and misidentified metabolites. Depending on the
      chemical analytical choices (sample extraction, chromatography, instrument and
      settings, etc.), only a partial representation of all metabolites will be
      achieved, biased by both the analytical methods and the database used to identify
      the metabolites. Here, we show on the one hand that using a data analysis
      approach based exclusively on pathway annotations has the potential to miss much
      that is of interest and, in the case of misidentified metabolites, can produce
      perturbed pathways that are statistically significant yet uninformative for the
      biological sample at hand. On the other hand, a targeted approach, by narrowing
      its focus and minimizing (but not eliminating) misidentifications, renders the
      likelihood of a spurious pathway much smaller, but the limited number of
      metabolites also makes statistical significance harder to achieve. To avoid an
      analysis dependent on pathways, we built a de novo network using all metabolites
      that were different at 24 h with and without estrogen with a p value <0.01 (53)
      in the STITCH database, which links metabolites based on known reactions in the
      main metabolic network pathways but also based on experimental evidence and text
      mining. The resulting network contained a "connected component" of 43 metabolites
      and helped identify non-endogenous metabolites as well as pathways not visible by
      annotation-based approaches. Moreover, the most highly connected metabolites
      (energy metabolites such as pyruvate and alpha-ketoglutarate, as well as amino
      acids) showed only a modest change between proliferation with and without
      estrogen. Here, we demonstrate that estrogen has subtle but potentially
      phenotypically important alterations in the acyl-carnitine fatty acids, acetyl
      putrescine and succinoadenosine, in addition to likely subtle changes in key
      energy metabolites that, however, could not be verified consistently given the
      technical limitations of this approach. Finally, we show that a network-based
      approach combined with text mining identifies pathways that would otherwise
      neither be considered statistically significant on their own nor be identified
      via ORA, QEA, or PA.

PMID- 27039106
TI  - Globally invasive, withdrawing at home: Aedes albopictus and Aedes japonicus
      facing the rise of Aedes flavopictus.
AB  - It has been suggested that climate change may have facilitated the global
      expansion of invasive disease vectors, since several species have expanded their
      range as temperatures have warmed. Here, we present results from observations on
      two major global invasive mosquito vectors (Diptera: Culicidae), Aedes albopictus
      (Skuse) and Aedes japonicus (Theobald), across the altitudinal range of Mt.
      Konpira, Nagasaki, Japan, a location within their native range, where Aedes
      flavopictus Yamada, formerly a rare species, has now become dominant. Spatial
      abundance patterns of the three species suggest that temperature is an important
      factor influencing their adult distribution across the altitudinal range of Mt.
      Konpira. Temporal abundance patterns, by contrast, were associated with rainfall
      and showed signals of density-dependent regulation in the three species. The
      spatial and temporal analysis of abundance patterns showed that Ae. flavopictus
      and Ae. albopictus were negatively associated, even when accounting for
      differential impacts of weather and other environmental factors in their co
      occurrence patterns. Our results highlight a contingency in the expansion of
      invasive vectors, the potential emergence of changes in their interactions with
      species in their native communities, and raise the question of whether these
      changes might be useful to predict the emergence of future invasive vectors.

PMID- 27039107
TI  - The Eating Disorder Examination Questionnaire: reliability and validity of the
      Italian version.
AB  - PURPOSE: To examine the validity and reliability of a new Italian language
      version of the latest edition of the Eating Disorder Examination Questionnaire
      (EDE-Q 6.0). METHODS: The sixth edition of the EDE-Q was translated into Italian
      and administered to 264 Italian-speaking inpatient and outpatient (257 females in
      their mid-20s) with eating disorder (75.4% anorexia nervosa) and 216 controls
      (205 females). RESULTS: Internal consistency was high for both the global EDE-Q
      and all subscale scores. Test-retest reliability was good to excellent (0.66
      0.83) for global and subscale scores, and for items assessing key behavioral
      features of eating disorders (0.55-0.91). Patients with an eating disorder
      displayed significantly higher EDE-Q scores than controls, demonstrating the good
      criterion validity of the tool. Confirmatory factor analysis revealed a good fit
      for a modified seven-item three-factor structure. CONCLUSIONS: The study showed
      the good psychometric properties of the new Italian version of the EDE-Q 6.0, and
      validated its use in Italian eating disorder patients, particularly in young
      females with anorexia nervosa.

PMID- 27039109
TI  - Anesthetic Management of an Acute Bleeding Ventriculo-Cutaneous Fistula.

PMID- 27039108
TI  - Genomic and physiological analysis reveals versatile metabolic capacity of deep
      sea Photobacterium phosphoreum ANT-2200.
AB  - Bacteria of the genus Photobacterium thrive worldwide in oceans and show
      substantial eco-physiological diversity including free-living, symbiotic and
      piezophilic life styles. Genomic characteristics underlying this variability
      across species are poorly understood. Here we carried out genomic and
      physiological analysis of Photobacterium phosphoreum strain ANT-2200, the first
      deep-sea luminous bacterium of which the genome has been sequenced. Using optical
      mapping we updated the genomic data and reassembled it into two chromosomes and a
      large plasmid. Genomic analysis revealed a versatile energy metabolic potential
      and physiological analysis confirmed its growth capacity by deriving energy from
      fermentation of glucose or maltose, by respiration with formate as electron donor
      and trimethlyamine N-oxide (TMAO), nitrate or fumarate as electron acceptors, or
      by chemo-organo-heterotrophic growth in rich media. Despite that it was isolated
      at a site with saturated dissolved oxygen, the ANT-2200 strain possesses four
      gene clusters coding for typical anaerobic enzymes, the TMAO reductases. Elevated
      hydrostatic pressure enhances the TMAO reductase activity, mainly due to the
      increase of isoenzyme TorA1. The high copy number of the TMAO reductase
      isoenzymes and pressure-enhanced activity might imply a strategy developed by
      bacteria to adapt to deep-sea habitats where the instant TMAO availability may
      increase with depth. 

PMID- 27039110
TI  - Delayed Paraplegia After Endovascular Treatment of a Thoracoabdominal Aortic
      Aneurysm Successfully Managed Using Cerebrospinal Fluid Drainage.

PMID- 27039111
TI  - Structural Defect Leading to an Impression of Iatrogenic Lung Damage.

PMID- 27039112
TI  - Therapeutic Efficacy of Chest Ultrasound and Chest X-Ray After Cardiac Surgery.

PMID- 27039113
TI  - Perioperative Management of Mitral Valve Replacement in an Individual With Bombay
      Phenotype.

PMID- 27039114
TI  - Prevalence of under-nutrition, associated factors and perceived nutritional
      status among elderly in a rural area of Puducherry, South India.
AB  - BACKGROUND: Under-nutrition among elderly goes undetected, despite their nature
      of vulnerability to it. Majority of the available literature assessed under
      nutrition in the facility based settings. We aimed to determine the prevalence of
      under-nutrition and its associated factors among elderly, in a rural setting.
      METHODS: A community based cross sectional survey was conducted among elderly in
      one of the randomly selected sub centre catchment area in rural Puducherry, south
      India. Information on socio demographic characteristics, morbidities and
      perception on their nutritional status were obtained. Anthropometric measures
      such as weight and arm span were measured by trained medical graduate as per the
      standard guidelines. Bodymass index (BMI) less than 18.5kg/m(2) was considered as
      under-nutrition. RESULTS: Of total 296 elderly in the study setting, 271 (92%)
      participated in the study. The prevalence of under nutrition among the elderly
      was 24.8% (95% CI: 19.7-30.3). More than half of the elderly (58.7%) perceived
      their nutritional status as poor; of them 28.9% were actually under-nourished.
      Mean (SD) BMI scores were higher for elderly women compared to that of men
      [elderly women vs men: 22 (4.6)kg/m(2) vs 21 (3.8)kg/m(2), p=0.03]. In
      multivariate analysis, being an elderly male, age more than 70 years and per
      capita income less than 1000 INR were found to be significantly associated with
      under-nutrition. CONCLUSION: In this rural area, one fourth of elderly were under
      nourished. Urgent inter-sectoral measures including food security programs are
      required to address this huge nutritional problem in this vulnerable group.

PMID- 27039115
TI  - Airway disorders of the fetus and neonate: An overview.
AB  - Differences between neonatal, pediatric and adult airway anatomy, structure and
      function are important to understand. Size, surface area, proportion, resistance
      and compliance are all very different between age groups and infants are
      certainly not small adults. Knowledge of these airway differences is essential in
      rapid correction of an emergency situation. Unanticipated airway emergencies are
      the most serious of all and may be classified into profiles such as the
      unanticipated emergency in the non-intubated patient, the unanticipated emergency
      in the intubated patient, and patients with tracheostomy. A neonatal airway
      emergency can be effectively managed by a strategy for anticipation,
      identification, preparation, mobilization, and execution. Furthermore, neonatal
      airways may be classified by severity in being considered either difficult or
      critical. These neonatal specific clinical challenges have recently substantiated
      the need for a distinct neonatal airway algorithm. This strategy is strengthened
      by regular education of the team and frequent simulation of airway emergencies.
      Following a predetermined pathway for activating an airway emergency alert and
      having all necessary equipment readily available are essential components of a
      well-defined strategy. Finally, knowing the pediatric otolaryngologist's
      perspective of what defines these airway disorders and current management is key
      to working collaboratively. 

PMID- 27039117
TI  - Preparation and characterization of an advanced collagen aggregate from porcine
      acellular dermal matrix.
AB  - The objective of this study was to extract and characterize an advanced collagen
      aggregate (Ag-col) from porcine acellular dermal matrix (pADM). Based on
      histological examination, scanning electron microscopy (SEM) and atomic force
      microscope (AFM), Ag-col was composed of the D-periodic cross-striated collagen
      fibrils and thick collagen fiber bundles with uneven diameters and non-orientated
      arrangement. Fourier transform infrared (FTIR) spectra of pADM, Ag-col and Col
      were similar and revealed the presence of the triple helix. Circular dichroism
      (CD) analysis exhibited a slightly higher content of alpha-helix but
      inappreciably less amount of random coil structure in Ag-col compared to Col.
      Moreover, imino acid contents of pADM, Ag-col and Col were 222.43, 218.30 and
      190.01 residues/1000 residues, respectively. From zeta potential analysis, a net
      charge of zero was found at pH 6.45 and 6.11 for Ag-col and Col, respectively.
      Differential scanning calorimetry (DSC) study suggested that the Td of Ag-col was
      20 degrees C higher than that of Col as expected, and dynamic mechanical analysis
      (DMA) indicated that Ag-col possessed a higher storage modulus but similar loss
      factor compared to Col. Therefore, the collagen aggregate from pADM could serve
      as a better alternative source of collagens for further applications in food and
      biological industries. 

PMID- 27039116
TI  - Substance Use Patterns Through Early Adulthood: Results for Youth With and
      Without Chronic Conditions.
AB  - INTRODUCTION: Adolescence and emergent adulthood are periods of peak prevalence
      for substance use that pose risks for short- and long-term health harm,
      particularly for youth with chronic medical conditions (YCMC) who are
      transitioning from adolescence to adulthood. As there have been no nationally
      representative studies of substance use during this period for these medically
      vulnerable youth, the authors sought to examine onset and intensification of
      these behaviors for a national sample of youth with and without chronic
      conditions. METHODS: Longitudinal data are from 2,719 youth between the ages of
      12 and 26 years interviewed from 2002 to 2011 for the Panel Study of Income
      Dynamics, Child Development and Transition to Adulthood Supplements, a nationally
      representative, population-based survey. Multivariate generalized linear mixed
      models were used to estimate patterns of alcohol, tobacco, and marijuana use
      during adolescence and emergent adulthood for youth with and without chronic
      conditions, adjusting for potential confounders. RESULTS: Overall, 68.8%, 44.3%,
      and 47.8% of youth reported ever trying alcohol, tobacco, and marijuana,
      respectively. Among users, 42.2%, 73.4%, and 50.3% of youth reported binge
      drinking, regular cigarette use, and recent marijuana use, respectively. YCMC
      were more likely to engage in any and heavier substance use; transition years and
      early adulthood were periods of peak risk for YCMC compared with their healthy
      peers. CONCLUSIONS: Substance use among YCMC during adolescence and emergent
      adulthood is a substantial concern. Increased prevention and case detection are
      in order to address these behaviors and promote optimal health outcomes for
      medically vulnerable youth.

PMID- 27039118
TI  - Polysaccharide-based bioflocculant template of a diazotrophic Bradyrhizobium
      japonicum 36 for controlled assembly of AgCl nanoparticles.
AB  - A simple and green method was developed for the biosynthesis of silver chloride
      nanoparticles, free from silver nanoparticles, using polysaccharide-based
      bioflocculant of a diazotrophic rhizobacteria Bradyrhizobium japonicum 36 strain.
      The synthesized silver chloride nanoparticles were characterized by UV-vis, XRD,
      FT-IR and TEM. The concentration-dependent and controllable method for silver
      chloride nanoparticles was developed. The biosynthesized silver chloride
      nanoparticles exhibited strong antimicrobial activity towards pathogenic
      microorganisms such as Escherichia coli, Staphylococcus aureus and Candida
      albicans. The synthesized silver chloride nanoparticles can be exploited as a
      promising new biocide bionanocomposite against pathogenic microorganisms. 

PMID- 27039119
TI  - An automated knowledge-based textual summarization system for longitudinal,
      multivariate clinical data.
AB  - OBJECTIVES: Design and implement an intelligent free-text summarization system:
      The system's input includes large numbers of longitudinal, multivariate, numeric
      and symbolic clinical raw data, collected over varying periods of time, and in
      different complex contexts, and a suitable medical knowledge base. The system
      then automatically generates a textual summary of the data. We aim to prove the
      feasibility of implementing such a system, and to demonstrate its potential
      benefits for clinicians and for enhancement of quality of care. METHODS: We have
      designed a new, domain-independent, knowledge-based system, the CliniText system,
      for automated summarization in free text of longitudinal medical records of any
      duration, in any context. The system is composed of six components: (1) A
      temporal abstraction module generates all possible abstractions from the
      patient's raw data using a temporal-abstraction knowledge base; (2) The abductive
      reasoning module infers abstractions or events from the data, which were not
      explicitly included in the database; (3) The pruning module filters out raw or
      abstract data based on predefined heuristics; (4) The document structuring module
      organizes the remaining raw or abstract data, according to the desired format;
      (5) The microplanning module, groups the raw or abstract data and creates
      referring expressions; (6) The surface realization module, generates the text,
      and applies the grammar rules of the chosen language. We have performed an
      initial technical evaluation of the system in the cardiac intensive-care and
      diabetes domains. We also summarize the results of a more detailed evaluation
      study that we have performed in the intensive-care domain that assessed the
      completeness, correctness, and overall quality of the system's generated text,
      and its potential benefits to clinical decision making. We assessed these
      measures for 31 letters originally composed by clinicians, and for the same
      letters when generated by the CliniText system. RESULTS: We have successfully
      implemented all of the components of the CliniText system in software. We have
      also been able to create a comprehensive temporal-abstraction knowledge base to
      support its functionality, mostly in the intensive-care domain. The initial
      technical evaluation of the system in the cardiac intensive-care and diabetes
      domains has shown great promise, proving the feasibility of constructing and
      operating such systems. The detailed results of the evaluation in the intensive
      care domain are out of scope of the current paper, and we refer the reader to a
      more detailed source. In all of the letters composed by clinicians, there were at
      least two important items per letter missed that were included by the CliniText
      system. The clinicians' letters got a significantly better grade in three out of
      four measured quality parameters, as judged by an expert; however, the variance
      in the quality was much higher in the clinicians' letters. In addition, three
      clinicians answered questions based on the discharge letter 40% faster, and
      answered four out of the five questions equally well or significantly better,
      when using the CliniText-generated letters, than when using the clinician
      composed letters. CONCLUSIONS: Constructing a working system for automated
      summarization in free text of large numbers of varying periods of multivariate
      longitudinal clinical data is feasible. So is the construction of a large
      knowledge base, designed to support such a system, in a complex clinical domain,
      such as the intensive-care domain. The integration of the quality and
      functionality results suggests that the optimal discharge letter should exploit
      both human and machine, possibly by creating a machine-generated draft that will
      be polished by a human clinician.

PMID- 27039120
TI  - The intestinal damage induced by lipid soluble meconium subfraction is profound
      compared to the intestinal damage induced by water soluble meconium subfraction.
AB  - BACKGROUND: It is unclear which substances in meconium are responsible for
      intestinal damage in gastroschisis. An experimental study was designed to
      investigate the effects of the lipid or water soluble subfractions of meconium on
      the intestines of gastroschisis in a chick model. METHODS: Meconium was pooled,
      homogenated, rota-evaporated dry and diluted. Meconium subfractions were obtained
      from water soluble and lipid soluble extracts of the meconium. Five days old
      fertilized chick embryos were used and divided into 5 groups: control, sham,
      water soluble meconium subfraction, lipid soluble meconium subfraction and whole
      meconium. All embryos were extirpated on the 18days and the intestines were
      harvested for histopathological examination. Serosal thickness was measured under
      light microscopy. RESULTS: Serosal thickness of the meconium (36.36+/-2.8MUm),
      the water soluble meconium (14.15+/-0.93MUm) and the lipid soluble meconium
      (23.88+/-1.69MUm) subfractions groups were significantly increased compared with
      the control (7.47+/-0.68MUm) and the sham (7.48+/-0.71MUm) groups (p<0.001).
      Serosal thickness of the lipid soluble meconium subfraction group was
      significantly increased compared with the water soluble meconium subfraction
      group (p<0.001). Serosal thickness of the meconium group was significantly
      increased compared to both the water and the lipid soluble meconium subfraction
      groups (p<0.001). CONCLUSION: Lipid soluble meconium subfraction induces more
      intestinal damage compared to water soluble meconium subfraction.

PMID- 27039121
TI  - Secondary signs may improve the diagnostic accuracy of equivocal ultrasounds for
      suspected appendicitis in children.
AB  - INTRODUCTION: Ultrasound (US) is the preferred imaging modality for evaluating
      appendicitis. Our purpose was to determine if including secondary signs (SS)
      improve diagnostic accuracy in equivocal US studies. METHODS: Retrospective
      review identified 825 children presenting with concern for appendicitis and with
      a right lower quadrant (RLQ) US. Regression models identified which SS were
      associated with appendicitis. Test characteristics were demonstrated. RESULTS:
      530 patients (64%) had equivocal US reports. Of 114 (22%) patients with equivocal
      US undergoing CT, those with SS were more likely to have appendicitis (48.6% vs
      14.6%, p<0.001). Of 172 (32%) patients with equivocal US admitted for
      observation, those with SS were more likely to have appendicitis (61.0% vs 33.6%,
      p<0.001). SS associated with appendicitis included fluid collection (adjusted
      odds ratio (OR) 13.3, 95% confidence interval (CI) 2.1-82.8), hyperemia (OR=2.0,
      95%CI 1.5-95.5), free fluid (OR=9.8, 95%CI 3.8-25.4), and appendicolith (OR=7.9,
      95%CI 1.7-37.2). Wall thickness, bowel peristalsis, and echogenic fat were not
      associated with appendicitis. Equivocal US that included hyperemia, a fluid
      collection, or an appendicolith had 96% specificity and 88% accuracy. CONCLUSION:
      Use of SS in RLQ US assists in the diagnostic accuracy of appendicitis. SS may
      guide clinicians and reduce unnecessary CT and admissions.

PMID- 27039122
TI  - Comparison of protocols for measuring cosmetic ingredient distribution in human
      and pig skin.
AB  - The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to
      improve the measurement and prediction of the bioavailability of topically
      exposed compounds for risk assessment. Key parameters of the experimental design
      of the skin penetration studies were compared. Penetration studies with frozen
      human and pig skin were conducted in two laboratories, according to the SCCS and
      OECD 428 guidelines. The disposition in skin was measured 24h after finite
      topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability
      distribution in skin layers of cold and radiolabelled chemicals were comparable.
      Furthermore, the distribution of each chemical was comparable in human and pig
      skin. The protocol was reproducible across the two laboratories. There were small
      differences in the amount of chemical detected in the skin layers, which were
      attributed to differences in washing procedures and anatomical sites of the skin
      used. In conclusion, these studies support the use of pig skin as an alternative
      source of skin should the availability of human skin become a limiting factor. If
      radiolabelled chemicals are not available, cold chemicals can be used, provided
      that the influence of chemical stability, reactivity or metabolism on the
      experimental design and the relevance of the data obtained is considered. 

PMID- 27039123
TI  - Bio-energy conversion performance, biodegradability, and kinetic analysis of
      different fruit residues during discontinuous anaerobic digestion.
AB  - Huge amounts of fruit residues are produced and abandoned annually. The high
      moisture and organic contents of these residues makes them a big problem to the
      environment. Conversely, they are a potential resource to the world. Anaerobic
      digestion is a good way to utilize these organic wastes. In this study, the
      biomethane conversion performances of a large number of fruit residues were
      determined and compared using batch anaerobic digestion, a reliable and easily
      accessible method. The results showed that some fruit residues containing high
      contents of lipids and carbohydrates, such as loquat peels and rambutan seeds,
      were well fit for anaerobic digestion. Contrarily, residues with high lignin
      content were strongly recommended not to be used as a single substrate for
      methane production. Multiple linear regression model was adopted to simulate the
      correlation between the organic component of these fruit residues and their
      experimental methane yield, through which the experimental methane yield could
      probably be predicted for any other fruit residues. Four kinetic models were used
      to predict the batch anaerobic digestion process of different fruit residues. It
      was shown that the modified Gompertz and Cone models were better fit for the
      fruit residues compared to the first-order and Fitzhugh models. The first
      findings of this study could provide useful reference and guidance for future
      studies regarding the applications and potential utilization of fruit residues. 

PMID- 27039124
TI  - Interval-parameter chance-constraint programming model for end-of-life vehicles
      management under rigorous environmental regulations.
AB  - As the number of end-of-life vehicles (ELVs) is estimated to increase to 79.3
      million units per year by 2020 (e.g., 40 million units were generated in 2010),
      there is strong motivation to effectively manage this fast-growing waste flow.
      Intensive work on management of ELVs is necessary in order to more successfully
      tackle this important environmental challenge. This paper proposes an interval
      parameter chance-constraint programming model for end-of-life vehicles management
      under rigorous environmental regulations. The proposed model can incorporate
      various uncertainty information in the modeling process. The complex
      relationships between different ELV management sub-systems are successfully
      addressed. Particularly, the formulated model can help identify optimal patterns
      of procurement from multiple sources of ELV supply, production and inventory
      planning in multiple vehicle recycling factories, and allocation of sorted
      material flows to multiple final destinations under rigorous environmental
      regulations. A case study is conducted in order to demonstrate the potentials and
      applicability of the proposed model. Various constraint-violation probability
      levels are examined in detail. Influences of parameter uncertainty on model
      solutions are thoroughly investigated. Useful solutions for the management of
      ELVs are obtained under different probabilities of violating system constraints.
      The formulated model is able to tackle a hard, uncertainty existing ELV
      management problem. The presented model has advantages in providing bases for
      determining long-term ELV management plans with desired compromises between
      economic efficiency of vehicle recycling system and system-reliability
      considerations. The results are helpful for supporting generation and improvement
      of ELV management plans. 

PMID- 27039125
TI  - Effects of the Novel Long-Acting GLP-1 Agonist, Albiglutide, on Cardiac Function,
      Cardiac Metabolism, and Exercise Capacity in Patients With Chronic Heart Failure
      and Reduced Ejection Fraction.
AB  - OBJECTIVES: This study sought to determine if glucagon-like peptide (GLP)-1
      ameliorates myocardial metabolic abnormalities in chronic heart failure.
      BACKGROUND: Albiglutide (GSK716155) is a GLP-1 agonist indicated for type 2
      diabetes. METHODS: We performed a randomized, placebo-controlled study evaluating
      12 weeks of albiglutide in New York Heart Association II or III subjects with
      ejection fraction <40%. Subjects received weekly placebo (n = 30) or albiglutide
      3.75 mg (n = 12), 15 mg (n = 13), or 30 mg (n = 27). The primary comparison was
      between albiglutide 30 mg and placebo. Assessments included echocardiography, 6
      minute-walk test, and peak oxygen consumption. In a subgroup of patients,
      myocardial glucose and oxygen use were assessed. Endpoints are reported as change
      from baseline +/- SE. RESULTS: Albiglutide 30 mg compared with placebo did not
      improve change from baseline in left ventricular ejection fraction (2.4% [1.1%]
      vs. 4.4% [1.1%]; p = 0.22), 6-min walk test (18 [12] m vs. 9 [11] m; p = 0.58),
      myocardial glucose use (p = 0.59), or oxygen use (p = 0.25). In contrast,
      albiglutide 30 mg versus placebo improved change from baseline in peak oxygen
      consumption (0.9 [0.5] ml/kg/min vs. -0.6 [0.5] ml/kg/min; p = 0.02). Albiglutide
      was well tolerated. CONCLUSIONS: Although there was no detectable effect of
      albiglutide on cardiac function or myocardial glucose use, there was a modest
      increase in peak oxygen consumption, which could have been mediated by noncardiac
      effects. (A Multi-center, Placebo-controlled Study to Evaluate the Safety of
      GSK716155 and Its Effects on Myocardial Metabolism, Myocardial Function, and
      Exercise Capacity in Patients With NYHA Class II/III Congestive Heart Failure;
      NCT01357850).

PMID- 27039126
TI  - QRS Duration Is a Predictor of Adverse Outcomes in Heart Failure With Preserved
      Ejection Fraction.
AB  - OBJECTIVES: This study examined the relationship between baseline QRS duration
      and clinical outcomes in subjects enrolled in the TOPCAT (Treatment of Preserved
      Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. BACKGROUND:
      Heart failure with preserved ejection fraction (HFPEF) is a heterogeneous
      clinical syndrome. Whether QRS duration identifies HFPEF subjects at an increased
      risk of adverse outcomes has not been well studied. METHODS: QRS duration was
      analyzed as a dichotomous variable (>=120 ms or <120 ms) and as a continuous
      variable to determine its relation to the primary outcome (composite of
      cardiovascular death, aborted cardiac arrest, or HF hospitalization [HFH]) and to
      each component of the primary outcome. Multivariate analyses were conducted in
      the entire study cohort as well as in separate analyses for subjects enrolled
      only from North and South America, or from Russia and Georgia. RESULTS: The QRS
      duration of >=120 ms was independently associated with an increased risk of the
      primary outcome (p = 0.009) and HFH (p = 0.003) in the entire study cohort and in
      the subset enrolled in the Americas. There was a linear relation of QRS duration
      with risk of the primary outcome and HFH. No interaction was observed between
      treatment with spironolactone and QRS duration. The risk of adverse outcomes was
      increased independently of the type of conduction abnormality underlying
      prolonged QRS duration. CONCLUSIONS: This post hoc analysis demonstrated that
      prolonged QRS duration identifies HFPEF subjects at a higher risk of adverse
      clinical outcomes and that spironolactone had a similar effect on outcomes
      independent of QRS duration. (Aldosterone Antagonist Therapy for Adults With
      Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).

PMID- 27039127
TI  - Digoxin Toxicity and Use of Digoxin Immune Fab: Insights From a National Hospital
      Database.
AB  - OBJECTIVES: This study was developed to determine contemporary management of
      digoxin toxicity and clinical outcomes. BACKGROUND: Although the use of digoxin
      in heart failure management has declined, toxicity remains a prevalent
      complication. METHODS: The Premier Perspective Comparative Hospital Database
      (Premier Inc., Charlotte, North Carolina) was used to retrospectively identify
      patients diagnosed with digoxin toxicity and/or who received digoxin immune fab
      (DIF) over a 5-year period (2007 to 2011). DIF was evaluated using treatment
      date, number of vials administered, and total cost. Clinical outcomes included
      length of stay (total hospitalization; days after DIF), cost of hospitalization,
      and in-hospital mortality. Exploratory multivariate analyses were conducted to
      determine predictors of DIF and effect on length of stay, adjusting for patient
      characteristics and selection bias. RESULTS: Digoxin toxicity diagnosis without
      DIF treatment accounted for 19,543 cases; 5,004 patients received DIF of whom
      3086 had a diagnosis of toxicity. Most patients were >65 years old (88%). The
      predictors of DIF use were urgent/emergent admission, hyperkalemia, arrhythmia
      associated with digoxin toxicity, acute renal failure, or suicidal intent (odds
      ratios 1.7, 2.4, 3.6, 2.1, and 3.7, respectively; p < 0.0001 for all). The
      majority (78%) of DIF was administered on days 1 and 2 of the hospitalization;
      10% received treatment after day 7. Digoxin was used after DIF administration in
      14% of cases. Among patients who received DIF within 2 days of admission, there
      was no difference for in-hospital mortality or length of stay compared with
      patients not receiving DIF. CONCLUSIONS: Digoxin toxicity diagnoses are clustered
      in the elderly. One-fifth of cases receive treatment with DIF, most within 2 days
      of admission. Opportunities exist for improved diagnosis and post-DIF management.
      Prospective data may be required to assess the impact of DIF on length of stay.

PMID- 27039128
TI  - Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With
      Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction.
AB  - OBJECTIVES: The objective of this study was to determine the cost-effectiveness
      and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan
      relative to enalapril for treatment of heart failure with reduced ejection
      fraction (HFrEF). BACKGROUND: Compared with enalapril, combination angiotensin
      receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan,
      reduces cardiovascular death and heart failure hospitalization rates in patients
      with HFrEF. METHODS: Using a Markov model, costs, effects, and cost-effectiveness
      were estimated for sacubitril-valsartan and enalapril therapies for the treatment
      of HFrEF. Patients were 60 years of age at model entry and were modeled over a
      lifetime (40 years) from a third-party payer perspective. Clinical probabilities
      were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With
      ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All
      costs and effects were discounted at a 3% rate annually and are presented in 2015
      U.S. dollars. RESULTS: In the base case, sacubitril-valsartan, compared with
      enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs.
      5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was
      highly dependent on duration of treatment, ranging from $249,411 per QALY at 3
      years to $50,959 per QALY gained over a lifetime. CONCLUSIONS: Sacubitril
      valsartan may be a cost-effective treatment option depending on the willingness
      to-pay threshold. Future investigations should incorporate real-world evidence
      with sacubitril-valsartan to further inform decision making.

PMID- 27039129
TI  - Use of High-Sensitivity Troponin T to Identify Patients With Acute Heart Failure
      at Lower Risk for Adverse Outcomes: An Exploratory Analysis From the RELAX-AHF
      Trial.
AB  - OBJECTIVES: The aim of this study was to determine if a baseline high-sensitivity
      troponin T (hsTnT) value <=99th percentile upper reference limit (0.014 MUg/l
      ["low hsTnT"]) identifies patients at low risk for adverse outcomes. BACKGROUND:
      Approximately 85% of patients who present to emergency departments with acute
      heart failure are admitted. Identification of patients at low risk might decrease
      unnecessary admissions. METHODS: A post-hoc analysis was conducted from the RELAX
      AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart
      Failure) trial, which randomized patients within 16 h of presentation who had
      systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N
      terminal pro-brain natriuretic peptide >=1,600 ng/l to serelaxin versus placebo.
      Linear regression models for continuous endpoints and Cox models for time-to
      event endpoints were used. RESULTS: Of the 1,076 patients with available baseline
      hsTnT values, 107 (9.9%) had low hsTnT. No cardiovascular (CV) deaths through day
      180 were observed in the low-hsTnT group compared with 79 CV deaths (7.3%) in
      patients with higher hsTnT. By univariate analyses, low hsTnT was associated with
      lower risk for all 5 primary outcomes: 1) days alive and out of the hospital by
      day 60; 2) CV death or rehospitalization for heart failure or renal failure by
      day 60; 3) length of stay; 4) worsening heart failure through day 5; and 5) CV
      death through day 180. After multivariate adjustment, only 180-day CV mortality
      remained significant (hazard ratio: 0.0; 95% confidence interval: 0.0 to 0.736; p
      = 0.0234; C-index = 0.838 [95% confidence interval: 0.798 to 0.878]).
      CONCLUSIONS: No CV deaths through day 180 were observed in patients with hsTnT
      levels <=0.014 MUg/l despite high N-terminal pro-brain natriuretic peptide
      levels. Low baseline hsTnT may identify patients with acute heart failure at very
      low risk for CV mortality.

PMID- 27039130
TI  - Championing Effectiveness Before Cost-Effectiveness.

PMID- 27039132
TI  - [Intestinal and peritoneal tuberculosis in a non-immunocompromised patient].

PMID- 27039131
TI  - In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients
      Hospitalized for Worsening Heart Failure: Insights From the EVEREST Trial.
AB  - OBJECTIVES: The aim of this study was to characterize the association between
      decongestion therapy and 30-day outcomes in patients hospitalized for heart
      failure (HF). BACKGROUND: Loop diuretic agents are commonly prescribed for the
      treatment of symptomatic congestion in patients hospitalized for HF, but the
      association between loop diuretic agent dose response and post-discharge outcomes
      has not been well characterized. METHODS: Cox proportional hazards models were
      used to estimate the association among average loop diuretic agent dose,
      congestion status at discharge, and 30-day post-discharge all-cause mortality and
      HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in
      the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study
      With Tolvaptan) study. RESULTS: In univariate analysis, subjects exposed to high
      dose diuretic agents (>=160 mg/day) had greater risk for the combined outcome
      than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio:
      2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for
      pre-specified covariates of disease severity, the association between diuretic
      agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence
      interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical
      assessments of volume status, 2,063 (69%) had little or no congestion at hospital
      discharge. Congestion status at hospital discharge did not modify the association
      between diuretic agent exposure and the combined endpoint (p for interaction =
      0.84). CONCLUSIONS: Short-term diuretic agent exposure during hospital treatment
      for worsening HF was not an independent predictor of 30-day all-cause mortality
      and HF rehospitalization in multivariate analysis. Congestion status at discharge
      did not modify the association between diuretic agent dose and clinical outcomes.

PMID- 27039133
TI  - Effects of omentectomy in addition to sleeve gastrectomy on the metabolic and
      inflammatory profiles of obese rats.
AB  - BACKGROUND: Visceral obesity has been considered a risk factor for metabolic and
      cardiovascular complications. In an attempt to reduce the visceral adipose
      tissue, omentectomy has been proposed to be performed along with bariatric
      surgery. OBJECTIVE: The goal of this study was to evaluate whether omentectomy
      associated with sleeve gastrectomy (SG) is beneficial to the inflammatory and
      metabolic profile of rats fed a standard diet (STD) or high-fat diet (HFD).
      SETTING: University hospital, Brazil. METHODS: For this experiment, male Wistar
      rats were randomly divided into 6 groups as follows: sham surgery (STD+L or
      HFD+L), SG alone (STD+SG or HFD+SG), or SG with omentectomy (STD+SGO or HFD+SGO).
      Anthropometric data and metabolic profiles were evaluated, and the tissue
      expression of inflammatory markers in the visceral adipose tissue was measured.
      RESULTS: In rats with diet-induced obesity treated with SG with or without
      omentectomy, there was a reduction in weight (HFD+SG: P<.01 and HFD+SGO: P<.05),
      adiposity (HFD+SG: P<.001 and HFD+SGO: P<.05), plasma levels of glucose (HFD+SG:
      P<.01 and HFD+SGO: P<.01), plasma levels of C-peptide (HFD+SG: P<.01 and HFD+SGO:
      P<.001), plasma levels of insulin (HFD+SG: P<.05 and HFD+SGO: P<.001), plasma
      levels of total cholesterol (HFD+SG: P<.01 and HFD+SGO: P<.01), and tissue
      expression of TNF-alpha (HFD+SG: P<.001 and HFD+SGO: P<.01), but there was no
      statistically significant difference between the groups in which omentectomy was
      performed or was not. CONCLUSION: In this study, we did not observe additional
      beneficial effects due to omentectomy associated with SG in the metabolic profile
      and tissue expression of inflammatory markers.

PMID- 27039134
TI  - Influence of intertidal recreational fisheries and 'bouchot' mussel culture on
      bivalve recruitment.
AB  - In coastal environments, fishing and aquaculture may be important sources of
      disturbance to ecosystem functioning, the quantification of which must be
      assessed to make them more sustainable. In the Chausey Archipelago, France,
      recreational fishing and commercial shellfish farming are the only two evident
      anthropogenic activities, dominated by bivalve hand-raking and 'bouchot' mussel
      culture, respectively. This study evaluates the impact of both activities on
      bivalve recruitment dynamics by comparing primary recruitment intensity (short
      term effect) and recruitment efficiency (medium-term effect) by sampling bivalves
      in reference (undisturbed) and disturbed (i.e. subjected to hand-raking or in
      'bouchot' mussel culture areas) parcels throughout and at the end of the
      recruitment season, respectively. Specific hypotheses evaluated were that (H1)
      bivalve hand-raking negatively affects bivalve recruitment and that (H2)
      'bouchot' mussel culture promotes bivalve recruitment. Patterns in bivalve
      community structure in reference parcels (i.e. natural pattern) differed between
      initial and final recruitment, underlining the great importance of early post
      settlement processes, particularly secondary dispersal. Primary recruitment
      intensity was inhibited in hand-raking parcels whereas it was promoted in
      'bouchot' mussel culture parcels, but the effect on recruitment efficiency was
      muted for both activities due to post-settlement processes. Nevertheless, the
      importance of effects that occur during the first step of recruitment should not
      be ignored as they may affect bivalve communities and induce immediate
      consequences on the trophic web through a cascade effect. Finally, it is
      highlighted that hand-raking damages all life stages of the common cockle
      Cerastoderma edule, one of the major target species, suggesting that this
      activity should be managed with greater caution than is currently done. 

PMID- 27039135
TI  - Anthropometric measurements of the femur change with component positioning in
      total knee arthroplasty.
AB  - BACKGROUND: To analyze aspect ratio (AP size/ (ML) size) of osteoarthritic knees
      at four different areas of the femur and to observe if proximalization of the
      femoral cut would change the ML size as well as confirm that external rotation
      increases the measurements for the AP dimensions of the femur. METHOD: From the
      available MyKnee database (Medacta International, Castel San Pietro, Switzerland)
      1030 patients were randomly selected within 20 degrees  of deformity consisting
      of 400 men with a mean (SD) age of 67.5 (9) years and 630 women with a mean (SD)
      age of 69 (10) years (p<0.0001). A specific software program was developed to
      measure AP and ML dimensions of the femur on CT-scans for (3D) planning in four
      areas. The AP femoral size was measured with neutral axial rotation following the
      epicondylar axis and without accepting anterolateral notching. RESULTS:
      Proximalization of the femur resulted in no changes except for a larger ML3 area
      in men. Increased axial rotation increased the AP dimensions for the same femur
      by a mean (SD) 2.5 (1) mm for males and females. CONCLUSIONS: The crucial area
      for overhang of the femoral component is the anterior region (ML1) with an aspect
      ratio of about +/-, but with an important range. Proximalization of the femoral
      cut is not accompanied by narrowing of the anterior femur but ML widening of the
      more posterior femur in men. Increased external rotation leads to a measurement
      of bigger AP size leading to an AP versus ML mismatch and change in aspect ratio.

PMID- 27039136
TI  - Novel electrospun nanofibrous matrices prepared from poly(lactic
      acid)/poly(butylene adipate) blends for controlled release formulations of an
      anti-rheumatoid agent.
AB  - In the present work, a series of novel formulations consisting of poly(lactic
      acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as
      controlled release matrices for Leflunomide's active metabolite, Teriflunomide
      (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order
      to produce nanofibrous matrices with different characteristics. Miscibility
      studies of the blended polymeric fibers were performed through differential
      scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation
      in the prepared fibers was evaluated at 37 degrees C using a phosphate buffered
      saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were
      incorporated into nanofibers for examining the drug release behavior in simulated
      body fluids (SBF), at 37 degrees C. The drug-loaded nanofibrous formulations were
      further characterized by Fourier Transform Infrared Spectroscopy (FTIR)
      spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used
      to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and
      multi-linear-regression (MLR) models were used to evaluate the effect of %
      content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution
      behavior. It was found that PLA/PBAd nanofibers have different diameters
      depending on the ratio of used polyesters and added drug. TFL was incorporated in
      an amorphous form inside the polymeric nanofibers. In vitro release studies
      reveal that a drug release behavior is correlated with the size of the
      nanofibers, drug loading and matrix degradation after a specific time. ANN
      dissolution modeling showed increased correlation efficacy compared to MLR. 

PMID- 27039137
TI  - Spontaneous rupture of an internal laryngocele after neck dissection: a rare
      complication.
AB  - We present a rare, and to the best of our knowledge, previously unreported
      complication of the spontaneous rupture of an internal laryngocele after a
      routine neck dissection for metastatic squamous cell carcinoma. While this caused
      some diagnostic confusion, the patient was managed conservatively with no further
      complications.

PMID- 27039138
TI  - PCSK9 Inhibitors for Statin Intolerance?

PMID- 27039139
TI  - Contextual modulation of motor resonance during the observation of everyday
      actions.
AB  - Neuroimaging studies on action observation suggest that context plays a key role
      in coding high-level components of motor behavior, including the short-term and
      the end-goal of an action. However, little is known about the possible role of
      context in shaping lower-levels of action processing such as reading action
      kinematics and simulating muscular activity. Here, we combined single-pulse TMS
      and motor-evoked potentials (MEPs) recording to explore whether top-down
      contextual information is capable of modulating low-level motor representations.
      We recorded MEPs from FDI and FCR muscles while participants watched videos about
      everyday actions embedded in congruent, incongruent or ambiguous contexts. Videos
      were interrupted before action ending, and participants were requested to predict
      the course of the observed action. A contextual modulation of corticospinal
      excitability was observed only for the FDI muscle, which is specifically involved
      in the execution of reaching-to-grasping movements, and whose corticospinal
      pathway is influenced by the observation of the very same movements. This
      modulation was reflected in a selective decrease of corticospinal excitability
      during the observation of actions embedded in incongruent as compared to
      congruent and ambiguous contexts. These findings indicate that motor resonance is
      not an entirely automatic process, but it can be modulated by high-level
      contextual representations.

PMID- 27039140
TI  - People matter: Perceived sender identity modulates cerebral processing of socio
      emotional language feedback.
AB  - How do human brains integrate content with social context in communication?
      Recent research demonstrates that the perceived communicative embedding of
      perceptually identical language messages alters their cortical processing. When
      emotional trait-adjectives are perceived as human-generated personality feedback,
      event-related brain potentials are considerably larger than when the same
      adjectives are perceived as random computer-generated feedback. Here, we
      investigate the unique role of ascribed sender humanness for the underlying
      neural mechanisms. Participants were told that they were going to receive written
      positive, negative, or neutral feedback from an unknown stranger or from a
      socially intelligent computer system while high-density EEG was recorded. In the
      event-related potential (ERP), feedback from the 'human sender' elicited larger
      P2, Early Posterior Negativity (EPN), P3, and Late Positive Potential (LPP)
      components. The sources of this activity were localized in extended visual
      cortex, but also in the right superior frontal gyri, related to mentalizing about
      others, and the bilateral postcentral gyri implicated in embodied language
      processing. For emotional feedback, larger EPN, P3 and LPP amplitudes were also
      observed, resulting from enhanced activity in visual and temporal regions.
      Finally, for the EPN an interaction between sender and emotion was found, showing
      substantially increased visual processing of human-generated emotional feedback.
      These data confirm visual amplification effects induced by motivated attention
      but crucially also reveal distinct effects of perceiving a communication partner
      as human that activate 'social brain' structures. Obviously who is perceived as
      saying something can be as relevant as what is said and induce specific brain
      activity.

PMID- 27039141
TI  - Trails of meaning construction: Symbolic artifacts engage the social brain.
AB  - Symbolic artifacts present a challenge to theories of neurocognitive processing
      due to their hybrid nature: they are at the same time physical objects and
      vehicles of intangible social meanings. While their physical properties can be
      read of their perceptual appearance, the meaning of symbolic artifacts depends on
      the perceiver's interpretative attitude and embeddedness in cultural practices.
      In this study, participants built models of LEGO bricks to illustrate their
      understanding of abstract concepts. They were then scanned with fMRI while
      presented to photographs of their own and others' models. When participants
      attended to the meaning of the models in contrast to their bare physical
      properties, we observed activations in mPFC and TPJ, areas often associated with
      social cognition, and IFG, possibly related to semantics. When contrasting own
      and others' models, we also found activations in precuneus, an area associated
      with autobiographical memory and agency, while looking at one's own collective
      models yielded interaction effects in rostral ACC, right IFG and left Insula.
      Interestingly, variability in the insula was predicted by individual differences
      in participants' feeling of relatedness to their fellow group members during LEGO
      construction activity. Our findings support a view of symbolic artifacts as neuro
      cognitive trails of human social interactions.

PMID- 27039142
TI  - Temporal context processing within hippocampal subfields.
AB  - The episodic memory system can differentiate similar events based on the temporal
      information associated with the events. Temporal context, which is at least
      partially determined by the events that precede or follow the critical event, may
      be a cue to differentiate events. The purpose of the present study is to
      investigate whether the hippocampal dentate gyrus (DG)/CA3 and CA1 subfields are
      sensitive to changes in temporal context and, if so, whether the subregions show
      a linear or threshold-like response to similar temporal contexts. Participants
      incidentally encoded a series of object picture triplets and 20 of them were
      included in final analyses. The third picture in each triplet was operationally
      defined as the target and the first two pictures served as temporal context for
      the target picture. Each target picture was presented twice with temporal context
      manipulated to be either repeated, high similarity, low similarity, or new on the
      second presentation. We extracted beta parameters for the repeated target as a
      function of the type of temporal context. We expected to see repetition
      suppression, a reduction in the beta values, in response to repetition of the
      target. If temporal context information is included in the representation of the
      target within a given region, this repetition suppression should be greater for
      target images that were preceded by their original context than for target images
      preceded by a new context. Neuroimaging results showed that CA1, but not DG/CA3,
      modifies the target's representation based on its temporal context. Right CA1 did
      not distinguish high similarity temporal context from repeated context but did
      distinguish low similarity temporal context from repeated context. These results
      indicate that CA1 is sensitive to temporal context and suggest that it does not
      differentiate between a substantially similar temporal context and an identical
      temporal context. In contrast, DG/CA3 does not appear to process temporal context
      as defined in the current experiment.

PMID- 27039143
TI  - Sleep in children triggers rapid reorganization of memory-related brain
      processes.
AB  - Behavioral evidence shows that sleep is crucial for the consolidation of
      declarative memories in children as in adults. However, the underlying cerebral
      mechanisms remain virtually unexplored. Using magnetoencephalography, we
      investigated in children (8.0-12.5years) the impact of sleep (90-minute nap) on
      the neurophysiological processes underlying the creation and consolidation of
      novel associations between unknown objects and their functions. Learning
      dependent changes in brain activity were observed within hippocampal and
      parahippocampal regions, followed by sleep-dependent changes in the prefrontal
      cortex, whereas no equivalent change was observed after a similar period of
      wakeful rest. Hence, our results show that in school-age children a 90-minute
      daytime nap after learning is sufficient to trigger the reorganization of memory
      related brain activity toward prefrontal areas, where it incorporates into pre
      existing semantic knowledge. This functional reorganization process in children
      is similar to that observed in adults but occurs at a much faster rate, which may
      contribute to the development of the impressive learning skills that characterize
      childhood.

PMID- 27039144
TI  - Interpersonal frontopolar neural synchronization in group communication: An
      exploration toward fNIRS hyperscanning of natural interactions.
AB  - Research of interpersonal neural synchronization (INS) using functional near
      infrared spectroscopy (fNIRS) hyperscanning is an expanding nascent field. This
      field still requires the accumulation of findings and establishment of analytic
      standards. In this study, we therefore intend to extend fNIRS-based INS research
      in three directions: (1) verifying the enhancement of frontopolar INS by natural
      and unstructured verbal communication involving more than two individuals; (2)
      examining timescale dependence of the INS modulation; and (3) evaluating the
      effects of artifact reduction methods in capturing INS. We conducted an fNIRS
      hyperscanning study while 12 groups of four subjects were engaged in cooperative
      verbal communication. Corresponding to the three objectives, our analyses of the
      data (1) confirmed communication-enhanced frontopolar INS, as expected from the
      region's roles in social communication; (2) revealed the timescale dependency in
      the INS modulation, suggesting the merit of evaluating INS in fine timescale
      bins; and (3) determined that removal of the skin blood flow component engenders
      substantial improvement in sensitivity to communication-enhanced INS and
      segregation from artifactual synchronization, and that caution for artifact
      reduction preprocessing is needed to avoid excessive removal of the neural
      fluctuation component. Accordingly, this study provides a prospective technical
      basis for future hyperscanning studies during daily communicative activities.

PMID- 27039145
TI  - Neuronal interactions in areas of spatial attention reflect avoidance of disgust,
      but orienting to danger.
AB  - For survival, it is necessary to attend quickly towards dangerous objects, but to
      turn away from something that is disgusting. We tested whether fear and disgust
      sounds direct spatial attention differently. Using fMRI, a sound cue (disgust,
      fear or neutral) was presented to the left or right ear. The cue was followed by
      a visual target (a small arrow) which was located on the same (valid) or opposite
      (invalid) side as the cue. Participants were required to decide whether the arrow
      pointed up- or downwards while ignoring the sound cue. Behaviorally, responses
      were faster for invalid compared to valid targets when cued by disgust, whereas
      the opposite pattern was observed for targets after fearful and neutral sound
      cues. During target presentation, activity in the visual cortex and IPL increased
      for targets invalidly cued with disgust, but for targets validly cued with fear
      which indicated a general modulation of activation due to attention. For the TPJ,
      an interaction in the opposite direction was observed, consistent with its role
      in detecting targets at unattended positions and in relocating attention. As a
      whole our results indicate that a disgusting sound directs spatial attention away
      from its location, in contrast to fearful and neutral sounds.

PMID- 27039146
TI  - Thinking about the thoughts of others; temporal and spatial neural activation
      during false belief reasoning.
AB  - Theory of Mind (ToM) is the ability to understand the perspectives, mental states
      and beliefs of others in order to anticipate their behaviour and is therefore
      crucial to social interactions. Although fMRI has been widely used to establish
      the neural networks implicated in ToM, little is known about the timing of ToM
      related brain activity. We used magnetoencephalography (MEG) to measure the
      neural processes underlying ToM, as MEG provides very accurate timing and
      excellent spatial localization of brain processes. We recorded MEG activity
      during a false belief task, a reliable measure of ToM, in twenty young adults (10
      females). MEG data were recorded in a 151 sensor CTF system (MISL, Coquitlam, BC)
      and data were co-registered to each participant's MRI (Siemens 3T) for source
      reconstruction. We found stronger right temporoparietal junction (rTPJ)
      activations in the false belief condition from 150ms to 225ms, in the right
      precuneus from 275ms to 375ms, in the right inferior frontal gyrus from 200ms to
      300ms and the superior frontal gyrus from 300ms to 400ms. Our findings extend the
      literature by demonstrating the timing and duration of neural activity in the
      main regions involved in the "mentalizing" network, showing that activations
      related to false belief in adults are predominantly right lateralized and onset
      around 100ms. The sensitivity of MEG will allow us to determine spatial and
      temporal differences in the brain processes in ToM in younger populations or
      those who demonstrate deficits in this ability.

PMID- 27039147
TI  - Study of the interactions of PAMAM G3-NH2 and G3-OH dendrimers with 5
      fluorouracil in aqueous solutions.
AB  - The results of spectroscopic measurements (increase in solubility, equilibrium
      dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration
      ITC) indicate spontaneous (DeltaG<0) bonding of 5-fluorouracil by both cationic
      PAMAM G3-NH2 dendrimer and hydroxyl PAMAM G3-OH dendrimer in aqueous solutions.
      PAMAM G3-NH2 dendrimer bonds about n= 25+/-8 drug molecules. Some of them n1= 5+/
      1 are bonded by terminal amine groups with equilibrium constant K1= 3890+/-930,
      while the remaining ones n2= 24 +/-3 are bonded by amide groups with equilibrium
      constant K2= 110+/-30. Hydroxyl PAMAM G3-OH dendrimer bonds n=6.0+/-1.6 molecules
      of 5-fluorouracil through tertiary amine groups with equilibrium constant K= 65+/
      10. The parameters of bonding 5-fluorouracil by PAMAM G3-NH2 and G3-OH dendrimer
      were compared with those of bonding this drug by the macromolecules of PAMAM of
      generations G4-NH2, G5-NH2 and G5-OH. 

PMID- 27039148
TI  - Demonstration of the interactions between aromatic compound-loaded lipid
      nanocapsules and Acinetobacter baumannii bacterial membrane.
AB  - Acinetobacter baumannii is an important nosocomial pathogen that is resistant to
      many commonly-used antibiotics. One strategy for treatment is the use of aromatic
      compounds (carvacrol, cinnamaldehyde) against A. baumannii. The aim of this study
      was to determine the interactions between bacteria and lipid nanocapsules (LNCs)
      over time based on the fluorescence of 3,3'-Dioctadecyloxacarbocyanine
      Perchlorate-LNCs (DiO-LNCs) and the properties of trypan blue to analyse the
      physicochemical mechanisms occurring at the level of the biological membrane. The
      results demonstrated the capacity of carvacrol-loaded LNCs to interact with and
      penetrate the bacterial membrane in comparison with cinnamaldehyde-loaded LNCs
      and unloaded LNCs. Modifications of carvacrol after substitution of hydroxyl
      functional groups by fatty acids demonstrated the crucial role of hydroxyl
      functions in antibacterial activity. Finally, after contact with the efflux pump
      inhibitor, carbonylcyanide-3-chlorophenyl hydrazine (CCCP), the results indicated
      the total synergistic antibacterial effect with Car-LNCs, showing that CCCP is
      associated with the action mechanism of carvacrol, especially at the level of the
      efflux pump mechanism. 

PMID- 27039149
TI  - Targeting, bio distributive and tumor growth inhibiting characterization of anti
      HER2 affibody coupling to liposomal doxorubicin using BALB/c mice bearing TUBO
      tumors.
AB  - Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of
      breast cancer tumors. In the current investigation, we exploited such a feature
      and utilized an anti-HER2 affibody (ZHER2:477) in combination with a pegylated
      liposomal doxorubicin (PLD) for concurrent passive and active targeting of HER2
      overexpressing TUBO tumor, using BALB/c mice. It was determined that the affibody
      coupled liposomes (affisomes) was capable of increasing doxorubicin (Dox)
      delivery to HER2+ cells (SK-BR-3 and TUBO cells), while transferring drug
      similarly as low as naive PLD to HER2- MDA-MB-231 cells. This also resulted in
      selectively enhance cytotoxicity. The veracity of targeting was further assessed
      utilizing DiD lipophilic tracer model liposomes via competition assay. An
      approximated 10 ligand/liposome integration caused Dox delivery at 50% of maximal
      delivery capacity (Kd). Such integration did not alter Dox release in vitro,
      while it affected the serum clearance profile. Affibody integration to PLD
      increased drug concentration in tumor and led to significantly further
      augmentation of drug in liver and spleen compared to those of PLD. Overall, such
      differences led to prolonging the mice life spans as compared to PLD. 

PMID- 27039150
TI  - Highly stable polyglutamate derivatives/siRNA polyplex efficiently down-relegate
      survivin expression and augment the efficacy of cisplatin.
AB  - RNA interfere (RNAi)-based technology holds great promise in cancer treatment.
      The use of small interfering RNA (siRNA), however, is hampered by its low
      delivery efficiency in vivo when they are diluted in blood biofluids and in the
      presence of serum and salt. In this study, we developed the polyglutamate
      derivative polymer brush, poly(ethyleneglycol) monomethyl ether-b-polyglutamate-g
      spermine (mPEG-b-PG-g-spermine, PPGS), which could efficiently deliver survivin
      siRNA under ultra-high dilution and in the presence of salt (NaCl 150mM) and
      serum (10% FBS), most likely due to its PEG-shelled polymer brush structure. On
      the contrary, aggregation occurred when PEI/siRNA polyplex dispersed in saline
      and serum-containing media and PEI polyplex dissociated after making a 256-fold
      dilution. PPGS/si-survivin polyplex exhibited high cellular uptake efficiency and
      efficiently down-regulated the expression of survivin mRNA in the cisplatin
      resistance of non-small cell human lung adenocarcinoma (A549/DDP) cells in the
      presence of serum. However, either PEI polyplex or Lipofectmine 2000 complex was
      unstable in serum and salt-containing media and at high dilution rates, which
      resulted in their dramatical decrease of cellular uptake and gene-silencing
      efficiency in these conditions. The PPGS/si-survivin polyplex also exhibited
      synergistic effects of killing the cancer cells by combination treatment with
      cisplatin. Therefore, the PPGS gene carrier showed great potential in systemic
      siRNA delivery, and its combination with chemotherapeutic drug is promising in
      treating drug resistant cancers. 

PMID- 27039151
TI  - Pharmacy and formulation support for paediatric clinical trials in England.
AB  - Availability and sourcing of investigational drugs for paediatric clinical trials
      is known to be a challenge for investigator-led clinical trials. The National
      Institute of Health Research Clinical Research Network: Children (CRN: Children)
      provides support for formulations and pharmacy related issues to researchers
      planning and setting up paediatric clinical trials within England. This paper
      reviews pharmacy and formulation support provided to a consecutive series of
      investigator-led clinical studies supported by CRN:Children. Case studies are
      included to describe some of the unique pharmaceutical challenges encountered. 44
      trials were reviewed and a total of 103 products were required to support these
      clinical trials. UK authorised products were suitable for use for 62 of these 103
      products. In the remaining 41 cases, 4 could be sourced as an authorised product
      within the European Union and the remaining 37 required bespoke manufacture.
      Bespoke manufacture of an investigational drug or placebo is costly. Typical
      costs for the initial development and testing of a bespoke investigational drug
      or placebo were in the range of L30,000-100,000 per product. The estimated cost
      for 19 out of 45 trials was available; in summary, the costs on a per patient per
      day of therapy basis ranged from under L1 to almost L600; short studies involving
      multiple agents are obviously the most expensive. This range is dependent upon
      the need for bespoke manufacture and also the number of participants within the
      trial. The arrangements for investigational drug supply can greatly affect the
      study design, regulatory requirements, trial logistics, as well as the total cost
      of research. As investigational product related activities are often costly,
      necessitating months of advance planning, it is imperative that specialist inputs
      are sought from the very start of the study design and planning process. 

PMID- 27039152
TI  - Functional roles and substrate specificities of twelve cytochromes P450 belonging
      to CYP52 family in n-alkane assimilating yeast Yarrowia lipolytica.
AB  - Yarrowia lipolytica possesses twelve ALK genes, which encode cytochromes P450 in
      the CYP52 family. In this study, using a Y. lipolytica strain from which all
      twelve ALK genes had been deleted, strains individually expressing each of the
      ALK genes were constructed and their roles and substrate specificities were
      determined by observing their growth on n-alkanes and analyzing fatty acid
      metabolism. The results suggested that the twelve Alk proteins can be categorized
      into four groups based on their substrate specificity: Alk1p, Alk2p, Alk9p, and
      Alk10p, which have significant activities to hydroxylate n-alkanes; Alk4p, Alk5p,
      and Alk7p, which have significant activities to hydroxylate the omega-terminal
      end of dodecanoic acid; Alk3p and Alk6p, which have significant activities to
      hydroxylate both n-alkanes and dodecanoic acid; and Alk8p, Alk11p, and Alk12p,
      which showed faint or no activities to oxidize these substrates. The involvement
      of Alk proteins in the oxidation of fatty alcohols and fatty aldehydes was also
      analyzed by measuring viability of the mutant deleted for twelve ALK genes in
      medium containing dodecanol and by observing growth on dodecanal of a mutant
      strain, in which twelve ALK genes were deleted along with four fatty aldehyde
      dehydrogenase genes. It was suggested that ALK gene(s) is/are involved in the
      detoxification of dodecanol and the assimilation of dodecanal. These results
      imply that genes encoding CYP52-family P450s have undergone multiplication and
      diversification in Y. lipolytica for assimilation of various hydrophobic
      compounds.

PMID- 27039153
TI  - A randomised control trial to compare retention rates of two cardiopulmonary
      resuscitation instruction methods in the novice.
AB  - BACKGROUND: Studies show that after implementation of chest compression only CPR
      (CCC) in the community, there was an increase in bystander CPR rates and survival
      of OHCA victims. There have been very few studies to compare the retention rates
      of CCC and conventional CPR (CVC) in lay people. METHODS: First year nursing
      students were randomised into one of the two CPR training methods: CVC - 30 chest
      compressions, followed by 2 mouth-to-mouth ventilations; and CCC - 100 chest
      compressions with 10s of rest before the next compression cycle. Within each
      group, they were sub-randomised into two groups for locating chest compression
      landmark: 2F - 2 finger-breadth proximal from xiphoid process, identified by
      tracing the lower margin of the victim's rib cage; or SL - shown the approximate
      location on the lower half of the sternum. 6 months later, participants underwent
      an unannounced test to perform one-man CPR on a moulaged mannikin. RESULTS:
      During the test, CVC groups did significantly fewer chest compressions per minute
      than CCC groups (57.8+/-23.7 vs 77.7+/-24.2, adjusted p<0.001). SL groups
      compressed significantly deeper than 2F groups (34.3+/-11.5cm vs 27.3+/-13.7cm,
      adjusted p<0.001), and was associated with higher rate of correct landmark for
      chest compression. 50.0% of the participants did not compress at the correct
      location. For those who were trained in CVC, only 3.7% were able to perform >=10
      effective ventilations in 5min. CONCLUSION: CCC, with SL as the method to locate
      landmark for chest compression, should be taught to lay people.

PMID- 27039154
TI  - Low cerebral activity and cerebral oxygenation during immediate transition in
      term neonates-A prospective observational study.
AB  - AIM: To analyze whether in term neonates during immediate transition after birth
      low cerebral activity measured by amplitude-integrated EEG (aEEG) is linked to
      cerebral regional oxygen saturation (crSO2) measured by near-infrared
      spectroscopy (NIRS). Additionally, the cerebral fractional tissue oxygen
      extraction (cFTOE) was calculated to analyze whether cerebral activity is linked
      to cFTOE. METHODS: A total of 244 term neonates delivered by primary cesarean
      section were studied. In addition to routine monitoring with pulse oximetry, aEEG
      and NIRS measurements were performed during the first 15min after birth. The mean
      minimum (Vmin) and maximum (Vmax) amplitude of the cerebral activity as well as
      crSO2 and cFTOE for each minute was determined. Neonates with initial Vmin<5MUV
      or Vmax<10MUV, which normalized during transition (study group) were compared to
      neonates with normal aEEG values throughout the whole monitoring period (control
      group). RESULTS: 9 neonates fulfilled inclusion criteria to the study group and
      were compared to 50 neonates in the control group. Vmin, Vmax, crSO2, SpO2 and
      cFTOE were compared from the 4th to 15thmin after birth. During our study period,
      Vmin and Vmax were significantly lower in the study group than in the control
      group. crSO2 was significantly lower in the study group until minute 11, dropping
      below the 10th centile in minute 8. cFTOE was significantly higher in the study
      group until minute 10, rising above the 90th centile in minutes 8 and 9. SpO2 was
      within normal ranges in both groups. crSO2 and cFTOE were within normal ranges in
      the control group. CONCLUSION: The present study demonstrates that neonates with
      initially low cerebral activity during immediate transition after birth
      concurrently showed low crSO2 (<10th percentile), but increased cerebral oxygen
      extraction (cFTOE>90th percentile). Cerebral monitoring with aEEG and NIRS might
      provide useful information on the neonates' condition during immediate
      transition.

PMID- 27039155
TI  - [Changes in drug management of Alzheimer's disease in nursing homes: Impact of
      the media campaign against specific drugs for Alzheimer's disease].
AB  - CONTEXT: Alzheimer's disease is a common disease in nursing homes. Evolution is
      constantly negative and specific treatments, which are only symptomatic, are
      subject to controversy. In a context of media exposure, the Transparency
      Committee of the Haute Autorite de sante (HAS) downgraded their medical service
      in October 2011, seeing it as weak. AIM: Assess the evolution of the consumption
      of specific treatments for Alzheimer's disease; assess changes in the quality of
      monitoring in specific consultation. METHODS: This is a retrospective and
      descriptive study, cross-sectional in three times (T0 January 2011, T1 October
      2011 and T2 June 2012), in 6 nursing homes of Lille and its surroundings.
      RESULTS: In total, 262 residents with dementia and present at least once during
      the three times of the study were included. Their mean age was 85.8 years. Among
      them, 40 % had Alzheimer's disease clearly identified. At T0, 76.7 % of patients
      present who were supposed to receive a specific treatment of Alzheimer's disease
      were actually receiving such treatment, 73.6 % at T1 and 71.6 % at T2. After 17
      months of observation, the discontinuation rate of anticholinesterase was 34 %,
      24 % for anti-glutamate. The monitoring in specific consultations decreased
      slightly between the three stages. CONCLUSION: Our work did not show major impact
      of the media campaign against specific drugs for Alzheimer's disease. There is
      however a trend towards a decrease of their consumption in people with dementia
      living in nursing homes with no obvious link between monitoring in specific
      consultation and specific prescription. This trend would ask to be confirmed by a
      study on a larger scale.

PMID- 27039156
TI  - Crayfish plague Aphanomyces astaci detected in redclaw crayfish, Cherax
      quadricarinatus in Taiwan.
AB  - Between December 2013 and January 2014, five outbreaks of an unknown disease with
      moderate to high cumulative mortality were observed among the freshwater redclaw
      crayfish (Cherax quadricarinatus) populations at four crayfish farms in Miaoli
      and Changhua counties (northern Taiwan) and at one crayfish farm in Pingtung
      County (southern Taiwan). Polymerase chain reaction (PCR) analysis allowed the
      detection of Aphanomyces astaci DNA in dead crayfish. Histopathological
      examination revealed an infection of host tissue by fungal hyphae that presented
      as typical non-septate hyphae within the soft abdominal cuticle from the first to
      second segment and in the tail fan. In PCR assays completed for the detection of
      crayfish plague, an expected 568-bp product, specific for the A. astaci ITS gene,
      was obtained from all sub-adults and adults examined. In a comparison of our
      strains with the known strains of A. astaci in Europe, nucleotide sequence
      identities were very similar, with 99.8-100% sequence similarity in that gene
      region. Positive reactions to in situ hybridization, using a digoxigenin (DIG)
      labelled DNA probe, further confirmed A. astaci as the causative agent. This is
      the first report concerning natural infection of A. astaci in freshwater redclaw
      crayfish in Asia.

PMID- 27039157
TI  - Co-managed Care for Medical Inpatients, C-L vs C/L Psychiatry.
AB  - OBJECTIVE: We report on a quality improvement program to co-manage patients with
      co-morbid medical and psychiatric disorders in the general hospital. A
      philanthropic donation allowed a high volume, high-acuity urban hospital to hire
      a co-managing inpatient psychiatrist. The expectation was that facilitating
      psychiatric evaluation/treatment of medical patients would result in fewer
      patients staying beyond the expected length of stay (LOS). METHOD: The
      psychiatrist became a member of a general medical team working with a group of
      internists and actively co-managing medical patients. After one year, we compared
      time-to-consultation request and LOS for patients seen through the traditional
      Consultation-Liaison model and patients seen through the co-managed care model. A
      second co-managing psychiatrist was hired. A new QI project investigated
      reduction in lost days. RESULTS: There was a decrease in LOS for patients seen in
      the co-managed care model when compared with those seen via the traditional
      Consultation-Liaison model. Co-managed patients were seen earlier in the
      hospitalization. Excluding very-long-stay outliers, there was a reduction in LOS
      of 1.19 days (p < 0.003). There was an estimated annualized saving to the
      hospital of 2889 patient days. CONCLUSIONS: A program of co-managed care reduced
      both LOS and lost days to the hospital. This resulted in an increase in hospital
      support to hire 2.5 full-time equivalent psychiatrists and 1.0 full-time
      equivalent social worker for the Consultation-Liaison service. Such programs may
      permit the return of modernized psychiatric liaison programs to medical and
      surgical services.

PMID- 27039158
TI  - Argyrophilic Grain Disease Presenting as Excited Catatonia: A Case Report.

PMID- 27039159
TI  - The transcriptome responses of cardiomyocyte exposed to hypothermia.
AB  - Hypothermia has positive and negative consequences on the body. Hypothermia
      depresses myocardial contraction, conduction, and metabolic rate in the heart.
      However, little is known about the underlying molecular mechanisms. Herein, we
      compared the gene expression of human adult ventricular cardiomyocytes (AC16)
      under hypothermia to find differences between different temperatures, and
      elucidate the candidate genes that may play important roles in the response to
      hypothermia. A total of 2413 differentially expressed genes (DEGs) were
      identified by microarray hybridization, which provided abundant data for further
      analysis. Gene Ontology (GO) enrichment analysis revealed that genes related to
      transcription, and protein and lipid metabolism were significantly enriched.
      Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were
      significantly enriched in TGF-beta pathway and cytokine-cytokine receptor
      interaction, which may play important roles in changes affected by hypothermia. A
      set of transcription factors (TFs) (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333,
      ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key
      nodes, which mapped the signal of hypothermia to transcriptome. The identified
      DEGs, pathways and predicted TFs could facilitate further investigations of the
      detailed molecular mechanisms.

PMID- 27039160
TI  - Association of dental infections with systemic diseases in Brazilian Native
      Indigenous: a cross-sectional study.
AB  - The aim of this cross-sectional study was to evaluate the association between
      dental infections and systemic diseases in the Indigenous population of Brazil. A
      representative sample of 225 Indigenous (>=19 years) was assessed. The T-test and
      bivariate and logistic models were used to assess the associations of diabetes,
      hypertension, and obesity with dental caries and destructive periodontal disease.
      After adjustments for covariates, dental caries were associated with hypertension
      (odds ratio = 1.95; 95% confidence interval: 1.03-3.66; P = .04). Individuals
      with destructive periodontal disease had a higher systolic blood pressure (124 +/
      20.34 mm Hg) than those without destructive periodontal disease (117.52 +/-
      16.54 mm Hg; P = .01). In conclusion, dental infections were found to be
      associated with hypertension in the present population. Thus, patients diagnosed
      with hypertension should be referred for dental evaluation and vice versa.

PMID- 27039161
TI  - Distance between rotator cuff footprints and the acromion, coracoacromial
      ligament, and coracoid process during dynamic arm elevations: Preliminary
      observations.
AB  - BACKGROUND: The objective of this study was to provide preliminary measures of
      the distance between the supraspinatus, infraspinatus, and subscapularis
      footprints and the acromion, coracoacromial ligament, and coracoid process,
      during dynamic arm elevations through the entire range-of-motion. METHODS: Two
      healthy men performed maximum adduction, flexion, abduction, and extension with
      the arm internally, neutrally, and externally rotated. The distance between each
      rotator cuff footprint and the acromion, coracoacromial ligament, and coracoid
      process was measured from glenohumeral kinematics obtained from markers fitted to
      intracortical pins combined with the scapular and humeral 3D geometry obtained
      from CT-scan. RESULTS: All footprints moved to be less than 10 mm to the
      acromion, coracoacromial ligament and coracoid process. They got closer to the
      acromion than to the other parts of the coracoacromial arch. The acromion
      supraspinatus and acromion-infraspinatus distances were minimal during abduction
      and flexion. The acromion-subscapularis distance was minimal when the arm was in
      external and neutral rotation during both adduction and flexion. CONCLUSIONS: The
      present study provides benchmark results of the distance between the rotator cuff
      footprints and the coracoacromial arch that may guide future clinical research.
      Pressure transducers should be positioned throughout the coracoacromial arch to
      provide comprehensive assessment of the compression undergone by the rotator cuff
      tendons. Common shoulder examination tests, that require flexion and internal
      rotation movements, may be refined since the supraspinatus footprint was the
      closest to the coracoacromial arch during abduction. Larger scale investigations
      may be needed to identify more accurate shoulder examination tests.

PMID- 27039162
TI  - Assessment of alpha-synuclein in submandibular glands of patients with idiopathic
      rapid-eye-movement sleep behaviour disorder: a case-control study.
AB  - BACKGROUND: The histological feature of Parkinson's disease is the presence of
      intraneuronal aggregates of phosphorylated alpha-synuclein (alphaSyn). In
      patients with Parkinson's disease, deposits of alphaSyn are found in the
      autonomic nerve fibres of the submandibular gland. Since patients with idiopathic
      rapid-eye-movement sleep behaviour disorder (IRBD) can develop Parkinson's
      disease and other synucleinopathies, we investigated whether alphaSyn deposits
      could also be detected in their submandibular gland nerve fibres. METHODS: We did
      a case-control study at the Hospital Clinic de Barcelona (Barcelona, Spain) in
      patients with polysomnographic-confirmed IRBD, patients with clinically diagnosed
      Parkinson's disease, and controls matched by age with the IRBD group. The
      controls were either healthy, had had elective neck surgery in the clinic, or
      were patients who had died in the clinic and had an autopsy. We did a
      transcutaneous core needle biopsy of the submandibular gland with ultrasound
      guidance in patients with IRBD or Parkinson's disease, and healthy controls, and
      without ultrasound guidance in the other controls. We assessed the presence of
      alphaSyn with immunohistochemistry using 129-phosphorylated antiserine monoclonal
      antibody, and analysed quantitative variables with Kruskall-Wallis tests and
      qualitative variables with Fisher's exact tests. FINDINGS: We did our study
      between July 16, 2014, and May 16, 2015, and recruited 21 patients with IRBD, 24
      patients with Parkinson's disease, and 26 controls (seven healthy, 11 patients
      undergoing neck surgery, and eight autopsies). We obtained submandibular biopsy
      material containing glandular parenchyma in nine (43%) of 21 patients with IRBD,
      12 (50%) of 24 patients with Parkinson's disease, and all (100%) of the 26
      controls. alphaSyn aggregates were detected in nerve fibres of the glandular
      parenchyma in eight (89%) of nine patients with IRBD and eight (67%) of 12 with
      Parkinson's disease, but none of the controls. Of the individuals whose biopsy
      samples did not contain glandular parenchyma, deposits of alphaSyn were found in
      extraglandular tissues in an additional three (25%) of 12 patients with IRBD and
      five (42%) of 12 patients with Parkinson's disease. None of the controls showed
      alphaSyn immunoreactivity in extraglandular tissues. Of the 52 participants who
      had ultrasonography-guided biopsy, 11 (21%) reported mild-to-moderate local pain,
      and nine (17%) developed a subcutaneous haematoma; however, these adverse events
      were transient and did not need treatment. INTERPRETATION: Our findings suggest
      that, in patients with IRBD, submandibular gland biopsy is a safe procedure for
      the detection of alphaSyn aggregates. alphaSyn detection could be useful for
      histological confirmation in individuals clinically diagnosed with Parkinson's
      disease. FUNDING: Centre for Networked Biomedical Research in Neurodegenerative
      Disorders (CIBERNED), Barcelona, Spain.

PMID- 27039163
TI  - Prefrontal transcranial direct current stimulation facilitates affective
      flexibility.
AB  - Performance on paradigms involving switching between emotional and non-emotional
      task-sets (affective flexibility) predicts emotion regulation abilities and is
      impaired in patients with different emotional disorders. A better understanding
      of how neurostimulation techniques such as transcranial direct current
      stimulation (tDCS) influence affective switching may provide support for the
      improvement of rehabilitation programs. In the current study healthy volunteers
      received anodal tDCS over the right dorsolateral prefrontal cortex (DLPFC), the
      left DLPFC or sham stimulation while performing an affective-switching task.
      Participants had to repeat or switch between facial judgments of emotional
      expressions (emotional task-set) or gender (non-emotional task-set). Right tDCS
      resulted in faster responses in the gender task only when it followed a judgment
      of emotion. These effects were not observed following left tDCS. Further,
      switching away from emotion was easier for the right compared to left tDCS group
      (reduced switch costs for gender), while switching away from gender toward
      emotion was easier for the left compared to the right group (reduced switch-costs
      for emotion). In sum, tDCS over the DLPFC may modulate affective flexibility and
      right stimulation may be particularly helpful to facilitate disengagement from
      emotional task-sets. The usefulness of tDCS-trained affective switching may be
      further investigated on larger therapeutic protocols targeting emotional
      disorders.

PMID- 27039164
TI  - The association between perceived social support and amygdala structure.
AB  - The subjective perception of social support plays a crucial role in human well
      being. However, its structural neural substrates remain unknown. We hypothesized
      that the amygdala, specifically its laterobasal and superficial subregions, which
      have been suggested to serve social functions, could be associated with the level
      of perceived social support. To test this hypothesis, we assessed perceived
      social support using the Multidimensional Scale of Perceived Social Support. In
      addition, we measured the volume and shape of the amygdala using structural
      magnetic resonance imaging in 49 healthy participants. Global amygdala volume in
      the left hemisphere was positively associated with the perceived social support
      score after adjusting for total cerebral volume, sex, age, intelligence, and five
      factor personality domains. The local shape of the laterobasal and superficial
      subregions of the left amygdala showed the same association with perceived social
      support. These data suggest that the social subregions of the left amygdala are
      associated with the implementation of perceived social support.

PMID- 27039165
TI  - Bioenergetic relevance of hydrogen sulfide and the interplay between
      gasotransmitters at human cystathionine beta-synthase.
AB  - Merely considered as a toxic gas in the past, hydrogen sulfide (H2S) is currently
      viewed as the third 'gasotransmitter' in addition to nitric oxide (NO) and carbon
      monoxide (CO), playing a key signalling role in human (patho)physiology. H2S can
      either act as a substrate or, similarly to CO and NO, an inhibitor of
      mitochondrial respiration, in the latter case by targeting cytochrome c oxidase
      (CcOX). The impact of H(2)S on mitochondrial energy metabolism crucially depends
      on the bioavailability of this gaseous molecule and its interplay with the other
      two gasotransmitters. The H(2)S-producing human enzyme cystathionine beta
      synthase (CBS), sustaining cellular bioenergetics in colorectal cancer cells,
      plays a role in the interplay between gasotransmitters. The enzyme was indeed
      recently shown to be negatively modulated by physiological concentrations of CO
      and NO, particularly in the presence of its allosteric activator S-adenosyl-l
      methionine (AdoMet). These newly discovered regulatory mechanisms are herein
      reviewed. This article is part of a Special Issue entitled 'EBEC 2016: 19th
      European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited
      by Prof. Paolo Bernardi.

PMID- 27039166
TI  - Impact of renal function on mean platelet volume and its relationship with
      coronary artery disease: A single-centre cohort study.
AB  - BACKGROUND: Mean platelet volume (MPV) has been proposed as a marker of platelet
      reactivity and cardiovascular disease. Chronic kidney disease (CKD) significantly
      favors the occurrence of cardiovascular events, by increasing the circulating
      levels of a wide spectrum of pro-oxidant and pro-thrombotic mediators. However,
      opposite alterations of platelet function, both enhanced aggregability and
      increased bleeding diathesis have been reported in these patients, with
      contrasting results on the effects of renal function on MPV and coronary artery
      disease, that were assessed in present study. METHODS: In patients undergoing
      coronary angiography, MPV and renal function (serum creatinine and estimated
      Glomerular Filtration Rate, eGFR, by MDRD formula) were assessed at admission.
      Coronary artery disease (CAD) was defined as a stenosis >50% in at least 1
      coronary vessel, while severe CAD as left main or trivessel disease. RESULTS:
      Among 3712 patients, 1044 (28.1%) had chronic kidney disease. CKD was related
      with age, female gender, diabetes and glycemic control, history of myocardial
      infarction, cerebrovascular accidents, coronary artery bypass grafting and left
      ventricular dysfunction or arrhythmias as indication to angiography, therapy with
      angiotensin-receptor blockers, nitrates, diuretics and calcium-antagonists, but
      lower rate of smoking, lower fibrinogen levels, haemoglobin, total and HDL
      cholesterol (p<0.001, respectively). CKD patients displayed increased severity
      and complexity of CAD (p<0.001) and significantly larger platelet volume
      (p<0.001), with CKD resulting as independent predictor of MPV above the median
      (>=10.85fl; Adjusted OR[95%CI]=1.56[1.23,1.99], p=0.002). Moreover, in the 1044
      patients with renal failure, higher platelet volume (above the median value;
      >=10.85fl) was associated with age (p=0.05), haemoglobin levels and platelet
      count (p<0.001), but not to a higher prevalence or extent of coronary artery
      disease (CAD: adjusted OR[95%CI]=0.80[0.58-1.09], p=0.16; severe CAD, adjusted
      OR[95%CI]=1.07[0.81-1.41], p=0.65). CONCLUSIONS: Higher values of MPV are
      observed among patients with chronic kidney disease, inversely relating to eGFR.
      However, larger platelet size does not contribute to explain the increased
      severity of coronary artery disease observed among these patients.

PMID- 27039167
TI  - Bergeyella porcorum sp. nov., isolated from pigs.
AB  - Four Gram-stain-negative, catalase- and oxidase-positive, bacillus-shaped
      bacterial isolates were recovered from the lungs and tonsils of four pigs. Based
      on cellular morphology and biochemical criteria the isolates were tentatively
      assigned to the genus Bergeyella, although the organisms did not appear to
      correspond with Bergeyella zoohelcum, the only validly named species of this
      genus. 16S rRNA gene sequencing demonstrated that isolates represented a distinct
      subline within the genus Bergeyella with <97%. 16S rRNA gene sequence similarity
      with B. zoohelcum ATCC 43767(T). The predominant cellular fatty acids of strain
      1350-03(T) were iso-C15:0 and iso-C17:0 3-OH and the major quinone was MK-6. The
      DNA G+C content of strain 1350-03(T) was 37.7mol%. The novel isolates can be
      phenotypically distinguished from B. zoohelcum based on physiological traits. On
      the basis of both phenotypic and phylogenetic findings, we describe a new species
      of the genus Bergeyella for which we propose the name of Bergeyella porcorum sp.
      nov. (1350-03(T)=CCUG 67887(T)=CECT 9006(T)). 

PMID- 27039168
TI  - Multiple acquisitions via sequential transfer of orphan spin polarization
      (MAeSTOSO): How far can we push residual spin polarization in solid-state NMR?
AB  - Conventional multidimensional magic angle spinning (MAS) solid-state NMR (ssNMR)
      experiments detect the signal arising from the decay of a single coherence
      transfer pathway (FID), resulting in one spectrum per acquisition time. Recently,
      we introduced two new strategies, namely DUMAS (DUal acquisition Magic Angle
      Spinning) and MEIOSIS (Multiple ExperIments via Orphan SpIn operatorS), that
      enable the simultaneous acquisitions of multidimensional ssNMR experiments using
      multiple coherence transfer pathways. Here, we combined the main elements of
      DUMAS and MEIOSIS to harness both orphan spin operators and residual polarization
      and increase the number of simultaneous acquisitions. We show that it is possible
      to acquire up to eight two-dimensional experiments using four acquisition periods
      per each scan. This new suite of pulse sequences, called MAeSTOSO for Multiple
      Acquisitions via Sequential Transfer of Orphan Spin pOlarization, relies on
      residual polarization of both (13)C and (15)N pathways and combines low- and high
      sensitivity experiments into a single pulse sequence using one receiver and
      commercial ssNMR probes. The acquisition of multiple experiments does not affect
      the sensitivity of the main experiment; rather it recovers the lost coherences
      that are discarded, resulting in a significant gain in experimental time. Both
      merits and limitations of this approach are discussed.

PMID- 27039169
TI  - Preferential processing of emotionally and self-relevant stimuli persists in
      unconscious N2 sleep.
AB  - Information processing has been suggested to depend on the current state of the
      brain as well as stimulus characteristics (e.g. salience). We compared processing
      of salient stimuli (subject's own names [SONs] and angry voice [AV] stimuli) to
      processing of unfamiliar names (UNs) and neutral voice (NV) stimuli across
      different vigilance stages (i.e. wakefulness as well as sleep stages N1 and N2)
      by means of event-related oscillatory responses during wakefulness and a
      subsequent afternoon nap. Our findings suggest that emotional prosody and self
      relevance drew more attentional resources during wakefulness with specifically AV
      stimuli being processed more strongly. During N1, SONs were more arousing than
      UNs irrespective of prosody. Moreover, emotional and self-relevant stimuli evoked
      stronger responses also during N2 sleep suggesting a 'sentinel processing mode'
      of the brain during this state of naturally occurring unconsciousness. Finally,
      this initial preferential processing of salient stimuli during N2 sleep seems to
      be followed by an inhibitory sleep-protecting process, which is reflected by a K
      complex-like response.

PMID- 27039170
TI  - High levels of the soluble programmed death-ligand (sPD-L1) identify
      hepatocellular carcinoma patients with a poor prognosis.
AB  - AIM: Immunotherapy in cancer is a recent and very promising approach, namely the
      inhibition of the PD/programmed death-ligand 1 (PD-L1) axis. Here we aimed to
      investigate the prognostic value of a soluble form of PD-L1 in hepatocellular
      carcinoma (HCC) patients. METHODS: HCC patients were prospectively recruited and
      soluble programmed death-ligand 1 (sPD-L1) levels were determined. sPD-L1 levels
      were compared to stages of cirrhosis and HCC. The association of the sPD-L1
      levels and overall survival (OS) was assessed. RESULTS: Two hundred fifteen
      patients with HCC were prospectively included. The median serum sPD-L1
      concentration in patients with HCC was 0.5 ng/ml (range 0.03-6.04). Soluble PD-L1
      levels positively correlated with the stage of cirrhosis and with stages of HCC.
      Furthermore, sPD-L1 correlated positively with a marker of macrophage activation
      (sCD163) and inflammation (C-reactive protein). The cut-off for high-level sPD-L1
      (>0.8 ng/ml) was defined by sPD-L1 levels determined in a healthy control cohort.
      Patients with high serum sPD-L1 concentrations had an increased mortality risk
      (hazard ratio 3.340, 95 % confidence interval 1.609-6.934, P<0.001), while very
      low PD-L1 levels seem to come along with better prognosis. High sPD-L1 levels
      were associated with mortality independently from cirrhosis stage, alpha
      fetoprotein and sCD163 levels in a multivariate Cox regression model.
      CONCLUSIONS: We conclude that a high sPD-L1 level is a possible prognostic
      indicator for a poor outcome in HCC patients. The predictive value of sPD-L1
      levels for a successful anti-PD1/PD-L1 therapy should be investigated in the
      future.

PMID- 27039171
TI  - Immunotherapy in gastrointestinal cancer: Recent results, current studies and
      future perspectives.
AB  - The new therapeutic approach of using immune checkpoint inhibitors as anticancer
      agents is a landmark innovation. Early studies suggest that immune checkpoint
      inhibition might also be effective in patients with gastrointestinal cancer. To
      improve the efficacy of immunotherapy, different strategies are currently under
      evaluation. This review summarises the discussion during the European
      Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer
      Translational Research Meeting in Mainz in November 2014 and provides an update
      on the most recent results of immune therapy in gastrointestinal cancers.
      Knowledge of potential relationships between tumour cells and their
      microenvironment including the immune system will be essential in
      gastrointestinal malignancies. In this context, the density of T cell
      infiltration within colorectal cancer metastases has been associated with
      response to chemotherapy, and a high expression of programmed cell death ligand 1
      (PD-L1) in advanced gastric cancer has been related with poor prognosis.
      Effective targets might include neo-antigens encoded from genes carrying tumour
      specific somatic mutations. Tailored immunotherapy based on such mutations could
      enable the effective targeting of an individual patient's tumour with vaccines
      produced on demand. Other strategies considering checkpoint inhibitors have shown
      efficacy by targeting cytotoxic T-lymphocyte-associated protein 4 and PD-1 or PD
      L1. DNA mismatch repair-deficient tumours appear to be potentially the best
      candidates for these therapies. Finally, the combination of oncolytic viruses
      with immunotherapy might boost antitumour activity as well. Further evaluation of
      these promising immunological therapeutic approaches will require large
      prospective clinical studies.

PMID- 27039172
TI  - Retracing the path of planar cell polarity.
AB  - BACKGROUND: The Planar Cell Polarity pathway (PCP) has been described as the main
      feature involved in patterning cell orientation in bilaterian tissues. Recently,
      a similar phenomenon was revealed in cnidarians, in which the inhibition of this
      pathway results in the absence of cilia orientation in larvae, consequently
      proving the functional conservation of PCP signaling between Cnidaria and
      Bilateria. Nevertheless, despite the growing accumulation of databases concerning
      basal lineages of metazoans, very few information concerning the existence of PCP
      components have been gathered outside of Bilateria and Cnidaria. Thus, the origin
      of this module or its prevalence in early emerging metazoans has yet to be
      elucidated. RESULTS: The present study addresses this question by investigating
      the genomes and transcriptomes from all poriferan lineages in addition to
      Trichoplax (Placozoa) and Mnemiopsis (Ctenophora) genomes for the presence of the
      core components of this pathway. Our results confirm that several PCP components
      are metazoan innovations. In addition, we show that all members of the PCP
      pathway, including a bona fide Strabismus ortholog (Van gogh), are retrieved only
      in one sponge lineage (Homoscleromorpha) out of four. This highly suggests that
      the full PCP pathway dates back at least to the emergence of homoscleromorph
      sponges. Consequently, several secondary gene losses would have occurred in the
      three other poriferan lineages including Amphimedon queenslandica (Demospongiae).
      Several proteins were not retrieved either in placozoans or ctenophores leading
      us to discuss the difficulties to predict orthologous proteins in basally
      branching animals. Finally, we reveal how the study of multigene families may be
      helpful to unravel the relationships at the base of the metazoan tree.
      CONCLUSION: The PCP pathway antedates the radiation of Porifera and may have
      arisen in the last common ancestor of animals. Oscarella species now appear as
      key organisms to understand the ancestral function of PCP signaling and its
      potential links with Wnt pathways.

PMID- 27039173
TI  - Salvage of bleeding renal allograft following biopsy, with suture technique: a
      case report.
AB  - BACKGROUND: Percutaneous renal biopsy is a valuable procedure in the management
      of and prognostication for patients with renal disease. Complications, although
      rare, occur with renal biopsies. Arteriovenous fistulas and heavy bleeding are
      notable complications. In this report, we describe simple suturing of the biopsy
      tract for salvage of a graft destined for a nephrectomy due to a profusely
      bleeding arteriovenous fistula. CASE PRESENTATION: A 20-year-old Sri Lankan man
      with end-stage renal disease due to steroid-resistant nephrotic syndrome
      underwent a renal transplant. He had poor urine output following the surgery, and
      a renal biopsy was performed to diagnose his renal pathology. He experienced
      poorly controlled postprocedural hypertension, and he had four episodes of gross
      hematuria that required blood transfusion. Coil embolization was delayed due to
      technical issues, and a graft nephrectomy was planned following the fourth
      episode of hematuria, which was the most severe. A Doppler scan revealed a
      slender, iatrogenic arteriovenous fistula corresponding to the biopsy tract, with
      very high flow rates. With knowledge of the anatomy of the fistula, we performed
      suturing of the tract to obliterate the fistula as a last resort to salvage the
      graft. The surgical procedure stopped the bleeding, and the patient made a full
      recovery with an excellent quality of life. CONCLUSIONS: In our patient, a renal
      transplant biopsy revealed acute tubular necrosis. The incidence and treatment of
      fistulas and differences in complication rates among native and graft kidney
      biopsies are discussed.

PMID- 27039174
TI  - Autocrine Sonic hedgehog signaling promotes gastric cancer proliferation through
      induction of phospholipase Cgamma1 and the ERK1/2 pathway.
AB  - BACKGROUND: Sonic hedgehog (SHH) plays critical roles in cell growth and
      development. Tumor cells express SHH, which can promote cell proliferation and
      epithelial-to-mesenchymal transition. However, the autocrine SHH pathway has not
      been described in gastric cancer. The aim of this study was to explore molecular
      mechanisms underlying autocrine SHH signaling in gastric cancer cells. METHODS:
      SHH expression was assessed using immunohistochemistry and the results were
      compared with clinicopathologic parameters, including survival. Using gastric
      cancer cell lines, we measured SHH mRNA and protein expression, and studied the
      effects of SHH signaling on cell proliferation and SHH secretion. We also studied
      the effects of an inhibitor of PLC-gamma1 on phosphorylation of phospholipase
      Cgamma1 and extracellular signal-regulated kinases (ERK)1/2. RESULTS: SHH protein
      expression in gastric cancer tissue was significantly higher compared with that
      in normal gastric tissue (P < 0.001), and the increased expression was
      significantly associated with pT staging (P = 0.004), pN staging (P = 0.018), pM
      staging (P = 0.006), and pTNM staging (P < 0.001). In multivariate analyses,
      overall survival in gastric cancer was significantly shorter in cases with high
      SHH expression (HR = 1.734, 95% CI: 1.109-2.713, P = 0.016). The AGS and SGC-7901
      gastric cancer cell lines expressed SHH mRNA and protein. In these cell lines,
      SHH promoted carcinogenesis through activation of the PLCgamma1-ERK1/2 pathway,
      resulting in increased cell proliferation and survival. CONCLUSIONS: Increased
      SHH expression is associated with shorter survival in gastric cancer patients,
      and SHH could represent a useful biomarker or therapeutic target for this
      disease.

PMID- 27039175
TI  - Characterization of the serum metabolome following radiation treatment in
      patients with high-grade gliomas.
AB  - BACKGROUND: Glioblastomas progress rapidly making response evaluation using MRI
      insufficient since treatment effects are not detectable until months after
      initiation of treatment. Thus, there is a strong need for supplementary
      biomarkers that could provide reliable and early assessment of treatment
      efficacy. Analysis of alterations in the metabolome may be a source for
      identification of new biomarker patterns harboring predictive information.
      Ideally, the biomarkers should be found within an easily accessible compartment
      such as the blood. METHOD: Using gas-chromatographic- time-of-flight-mass
      spectroscopy we have analyzed serum samples from 11 patients with glioblastoma
      during the initial phase of radiotherapy. Fasting serum samples were collected at
      admittance, on the same day as, but before first treatment and in the morning
      after the second and fifth dose of radiation. The acquired data was analyzed and
      evaluated by chemometrics based bioinformatics methods. Our findings were
      compared and discussed in relation to previous data from microdialysis in tumor
      tissue, i.e. the extracellular compartment, from the same patients. RESULTS: We
      found a significant change in metabolite pattern in serum comparing samples taken
      before radiotherapy to samples taken during early radiotherapy. In all, 68
      metabolites were lowered in concentration following treatment while 16
      metabolites were elevated in concentration. All detected and identified amino
      acids and fatty acids together with myo-inositol, creatinine, and urea were among
      the metabolites that decreased in concentration during treatment, while citric
      acid was among the metabolites that increased in concentration. Furthermore, when
      comparing results from the serum analysis with findings in tumor extracellular
      fluid we found a common change in metabolite patterns in both compartments on an
      individual patient level. On an individual metabolite level similar changes in
      ornithine, tyrosine and urea were detected. However, in serum, glutamine and
      glutamate were lowered after treatment while being elevated in the tumor
      extracellular fluid. CONCLUSION: Cross-validated multivariate statistical models
      verified that the serum metabolome was significantly changed in relation to
      radiation in a similar pattern to earlier findings in tumor tissue. However, all
      individual changes in tissue did not translate into changes in serum. Our study
      indicates that serum metabolomics could be of value to investigate as a potential
      marker for assessing early response to radiotherapy in malignant glioma.

PMID- 27039176
TI  - Early mortality in lung cancer: French prospective multicentre observational
      study.
AB  - BACKGROUND: Despite the progress seen in the last decade in diagnosis and
      treatment, lung cancer has still a bad prognosis and a substantial number of
      patients died within the weeks following diagnosis. The objective of this study
      was to quantify early mortality in lung cancer, to identify patients who are at
      high risk of early decease, and to describe their management in a real world.
      METHODS: Prospective observational study including consecutively all adult
      patients managed for primary lung cancer histologically or cytologically
      diagnosed in 2010 in the respiratory medicine department of one of the
      participating French general hospitals. Patients and cancer characteristics and
      first therapeutic strategy were collected at diagnosis. Dates of death were
      obtained from investigators or town council of the patient's birth place. All
      fatal cases were considered regardless of the cause of the death. Multivariate
      logistic regression model was used to determine the factors significantly and
      independently associated with death at 1 and 3 months. RESULTS: Seven thousand
      fifty-one patients from 104 centres were included in the study. Vital status was
      obtained for 6,981 patients. Respectively, 678 (9.7%) and 1,621 (23.2%) of the
      6,981 patients with available data died within 1 and 3 months following
      diagnosis. As compared with the other patients, they were significantly older and
      frailer (based on performance status [PS] and recent weight loss) and more
      frequently reported stage IV tumour. Overall, 64.5% (1 month) and 42.8% (3
      months) of patients had no cancer therapy and less than 1% were included in a
      therapeutic trial. CONCLUSION: About one in four patients died within 3 months
      following lung cancer diagnosis. Early mortality mainly involves frail patients
      with advanced cancer and is associated with lack of cancer therapy. This supports
      the need for early diagnosis and clinical trials in this population. Reducing
      early mortality to give supplementary time to patients to organise the future is
      a major challenge for 21(st) century physicians.

PMID- 27039177
TI  - A qualitative study on the background of long-term maintenance patients at a
      private Japanese dental clinic.
AB  - BACKGROUND: Continued periodontal maintenance after active therapy is highly
      important for maintaining a healthy oral function. In Japan, the rate of
      consultation for periodontal maintenance is remarkably low compared to other
      developed countries. This study analyzed the relationship between long-term
      maintenance and patient background characteristics in an effort to identify ways
      to increase the rate of consultation for periodontal maintenance in Japan.
      METHODS: Thirty-three long-term maintenance patients were interviewed. The
      interviews were recorded on video. The conversation between the patient and the
      interviewer was converted to text, and the data were qualitatively analyzed using
      the Steps for Coding and Theorization (SCAT) method. RESULTS: The mean age of the
      patients was 61.4 years and the average duration of maintenance was 10.7 years.
      The majority (90.9 %) of patients cared about their dietary habits, and 72.7 % of
      the patients understood the importance of physical activity. All of the patients
      wished to continue the maintenance, and 72.7 % of patients had good feelings
      about the staff of the dental clinic. However, their recognition of the
      description of primary prevention was low, with a response rate of only 21.2 %.
      CONCLUSIONS: The long-term maintenance patients had a high level of consciousness
      regarding their health and good feelings about the staff of the dental clinic.
      Oral hygienists, who are the main staff involved in periodontal maintenance were
      suggested to be important for increasing the maintenance consultation rate.

PMID- 27039178
TI  - Improved eating behaviours mediate weight gain prevention of young adults:
      moderation and mediation results of a randomised controlled trial of TXT2BFiT,
      mHealth program.
AB  - BACKGROUND: Explanatory evaluation of interventions for prevention of weight gain
      is required beyond changes in weight, to determine for whom the intervention
      works and the underlying mechanisms of change. It was hypothesised that
      participant characteristics moderate intervention effect on weight change and
      improved eating and physical activity behaviours during the 3-month program
      mediate the relationship between intervention and weight. METHODS: In our
      randomised controlled trial, young adults at risk of weight gain (n = 250) were
      assigned either to an intervention group that received a 3-month mHealth
      (TXT2BFiT) program with 6-month maintenance or to a control group. Data were
      collected via online self-report surveys. Hypothesised moderators and mediators
      of the intervention effect on weight were independently assessed in PROCESS macro
      models for 3 and 9-month weight change. RESULTS: Males (P = 0.01), mid-20s age
      group (P = 0.04), and higher income earners (P = 0.02) moderated intervention
      effects on weight change at 3-months and males only at 9-months (P = 0.02).
      Weight change at 3 (-1.12 kg) and 9-months (-1.38 kg) remained significant when 3
      month nutrition and physical activity behaviours were specified as mediators (P
      <0.01 and P = 0.01 respectively). Indirect paths explained 39% (0.72/1.85 kg) and
      40 % (0.92/2.3 kg) of total effect on weight change at 3 and 9-months
      respectively. Increased vegetable intake by intervention group at 3-months
      accounted for 19 and 17% and decreased sugar-sweetened beverages accounted for 8
      and 13% of indirect weight change effects at 3 and 9-months respectively.
      CONCLUSIONS: TXT2BFiT was effective for both young men and women. Small sustained
      behavioural changes, including increased vegetable intake and decreased sugar
      sweetened beverages consumption significantly mediated the intervention's effects
      on weight change. Improved eating behaviours and increased physical activity
      accounted for approximately 40% of the weight change. TRIAL REGISTRATION: The
      trial is registered with the Australian New Zealand Clinical Trials Registry (
      ACTRN12612000924853 ).

PMID- 27039179
TI  - The FcgammaR/IgG Interaction as Target for the Treatment of Autoimmune Diseases.
AB  - FcgammaRs are a crucial component of the antibody response as they mediate the
      cellular effector functions in response to IgG-containing immune complexes (ICs).
      Therefore, they also play a central role in the pathogenesis of autoimmune
      diseases which offers an attractive option to specifically target this class of
      molecules and their interaction with IgG for treatment of immune disorders. In
      detail, two strategies are discussed in this article. SM101, a soluble FcgammaR
      that is already in clinical development competes with the interaction of IgG with
      membrane FcgammaRs. Oppositely, SM201 recruits the inhibitory FcgammaRIIB for a
      broad down-modulation of the immune system. The presented approaches for the
      treatment of autoimmune diseases have the potential be more efficacious with
      fewer side effects than the currently used therapeutic options.

PMID- 27039180
TI  - Quality of life after aortic valve repair is similar to Ross patients and
      superior to mechanical valve replacement: a cross-sectional study.
AB  - BACKGROUND: In patients after aortic valve surgery, the quality of life is
      hypothesized to be influenced by the type of the valve procedure. A cross
      sectional study on the postoperative quality of life was carried out in patients
      after aortic valve-sparing surgery (with regards to the age of the patient), Ross
      procedure and mechanical aortic valve replacement. METHODS: Quality of life was
      studied in 139 patients after aortic valve surgery divided into four study groups
      (Y - aortic valve-sparing procedure at the age below 50 years, mean age 36.2
      years; O - aortic valve-sparing procedure at the age 50 years and over, mean age
      59.2 years; R - Ross procedure, mean age 37.8 years and M - mechanical aortic
      valve replacement at the age below 50 years, mean age 39.2 years). SF-36 Short
      Form and valve-specific questionnaires were mailed to the patients after 6 months
      or later following surgery (median 26.9 months). RESULTS: In SF-36, the younger
      aortic valve repair patients and the Ross patients scored significantly better in
      4 of 4 physical subscales and in 2 of 4 mental subscales than the older aortic
      valve repair and mechanical valve replacement patients. In the valve-specific
      questionnaire; however, all 3 groups free of anticoagulation (Y, O, and R)
      displayed greater freedom from negative valve-related concerns. CONCLUSIONS:
      Postoperative quality of life is influenced by the type of aortic valve procedure
      and is negatively linked with mechanical prosthesis implantation and long-term
      anticoagulation. Aortic valve-sparing strategy should be considered in cases with
      suitable valve morphology due to favorable clinical results and beneficial impact
      on the long-term quality of life.

PMID- 27039181
TI  - Exploring non-participation in primary care physical activity interventions: PACE
      UP trial interview findings.
AB  - BACKGROUND: Trials in primary care to increase physical activity (PA) typically
      experience poor recruitment rates and may not recruit those with lower PA levels
      and who are most in need of the intervention. Despite the well-publicised
      benefits of physical activity, the majority of adults in the UK remain inactive
      and, therefore, at greater risk of many health problems. Our aim was to
      investigate the reasons for non-participation in the PACE-UP trial, which is a
      primary care pedometer-based walking intervention. This is important for
      successful recruitment and retention in future PA trials and programmes. METHOD:
      We conducted semi-structured audio-recorded telephone interviews with 30
      participants, aged 45-75 years, purposively sampled from those declining
      participation in the PACE-UP trial. Recruitment continued until data saturation
      and a demographically balanced sample was achieved. Interviews were transcribed
      verbatim, coded and subjected to thematic analysis. RESULTS: Interviewees
      supported walking as suitable exercise for most people in this age group,
      recognised the importance of this type of research and general practice as an
      appropriate setting. Key reasons for declining were: the perception of being
      already 'too active'; existing medical conditions; work; travel and other
      commitments. Less frequently cited reasons included reluctance to be randomised,
      the intervention's duration, wearing a pedometer, perceived inappropriateness of
      trial literature and a preference for a different kind of PA or for a group
      activity. CONCLUSIONS: Whilst most interviewees perceived themselves to be
      sufficiently active, an important minority did not participate due to existing
      medical conditions and other commitments. Recruitment to future PA trials might
      be improved by tailoring activity to compensate for medical problems, and
      adapting PA interventions to fit around work and travel commitments. Ensuring
      that patient-targeted literature is succinct and inclusive and that equipment is
      user-friendly are also important. Primary care is seen as an appropriate setting
      for PA trials and programmes. TRIAL REGISTRATION: ISRCTN98538934 .

PMID- 27039183
TI  - Diagnosis of mycobacterial infections based on acid-fast bacilli test and
      bacterial growth time and implications on treatment and disease outcome.
AB  - BACKGROUND: The establishment of therapeutic regimens for mycobacteriosis depends
      on the accurate identification of Mycobacterium species, and misdiagnosis can
      result in inappropriate treatment and increased mortality of patients.
      Differential diagnosis among Mycobacterium species has been made by conventional
      phenotypic and biochemical tests after a long culture period. Specialized
      molecular diagnostics of mycobacteria allows rapid detection and species
      identification; however, such tests are not available in public health programs.
      Our aim was to demonstrate the clinical implications of erroneous diagnosis by
      performing molecular genotyping of mycobacterial infections in patients that were
      diagnosed based on symptoms, culture and bacilloscopy. METHODS: Culture samples
      of mycobacterial infections from 55 patients clinically diagnosed as tuberculosis
      in 2013 and 2014, based on conventional methods, were identified by PCR -RFLP and
      results are discussed. RESULTS: We have confirmed 35 (63.6%) positive samples as
      M. tuberculosis, but 18 (32.7%) were identified as non-tuberculous mycobacteria
      (M. avium type 1, M. avium type 2, M. kansasii type 1 type 1, M. mucogenicum, M.
      chelonae, M. terrae type 3, and 1 unknown RFLP pattern) and two were negative.
      Regarding clinical diagnosis, 61.8% (34/55) was classified as pulmonary
      tuberculosis. It is important to emphasize that 36.4% (20/55) of samples were
      misdiagnosed by conventional methods, and 11 (61.1%) of the HIV positive patients
      (18/55) were NTM-coinfected. CONCLUSION: The identification of species in
      mycobacterial infections is essential for correct diagnosis and choice of
      treatment regimen, and misdiagnosis by conventional tools can lead to chronic
      disease, increased resistance and death.

PMID- 27039182
TI  - Novel hyaluronic acid-methotrexate conjugate suppresses joint inflammation in the
      rat knee: efficacy and safety evaluation in two rat arthritis models.
AB  - BACKGROUND: Methotrexate (MTX) is one of the most widely used medications to
      treat rheumatoid arthritis (RA), and recent studies have also suggested the
      potential benefit of the drug for the treatment of osteoarthritis (OA) of the
      knee. MTX is commonly administered in oral formulations, but is often associated
      with systemic adverse reactions. In an attempt to address this issue, we have
      shown previously that a conjugate of hyaluronic acid (HA) and MTX exhibits
      potential as a drug candidate for intra-articular treatment of inflammatory
      arthritis. In this study, we compare the efficacy and safety of an optimized HA
      MTX conjugate, DK226, with that of MTX in inflammatory arthritis rat models.
      METHODS: In vitro activity of DK226 was assessed in human fibroblast-like
      synoviocytes (HFLS) and a synovial sarcoma cell line, SW982. Release of MTX from
      DK226 was investigated after incubation with rabbit synovial tissue homogenate or
      synovial fluid. In vivo efficacy of DK226 was evaluated in antigen-induced
      arthritis (AIA) and collagen-induced arthritis (CIA) in the rat knee.
      Pharmacokinetics and hematological toxicity after treatment with oral MTX or an
      intra-articular injection of DK226 were compared in AIA. RESULTS: Proliferation
      of HFLS and SW982 cells was inhibited by DK226, and the inhibitory activity was
      reversed by cotreatment with excess HA or anti-CD44 antibody. MTX was released
      from DK226 by incubation with rabbit synovial tissue homogenate or synovial fluid
      at pH 4.0, but not at pH 7.4. AIA was ameliorated by intra-articular DK226, but
      not by HA, as potently as oral MTX. Hematological toxicity was induced by oral
      MTX, but not by DK226. The maximum plasma concentration of MTX after oral MTX was
      40 times higher than the concentration of MTX after an intra-articular injection
      of DK226. Knee swelling in AIA was inhibited by intra-articular injections of
      DK226, but not by free MTX or a mixture of HA and MTX. In CIA, an injection of
      DK226 into the right knee joint significantly reduced swelling and synovial
      inflammation of the treated knee joint, but had no effect on the untreated
      contralateral knee joint. CONCLUSIONS: DK226 exerted anti-arthritic effects in
      two different models of arthritis. The conjugate had a wider therapeutic window
      than oral MTX, and could be a future drug for treatment of arthritic disorders,
      including inflammatory OA.

PMID- 27039184
TI  - OsPhyA modulates rice flowering time mainly through OsGI under short days and
      Ghd7 under long days in the absence of phytochrome B.
AB  - Phytochromes recognize light signals and control diverse developmental processes.
      In rice, all three phytochrome genes-OsphyA, OsphyB, and OsphyC-are involved in
      regulating flowering time. We investigated the role of OsPhyA by comparing the
      osphyA osphyB double mutant to an osphyB single mutant. Plants of the double
      mutant flowered later than the single under short days (SD) but bolted earlier
      under long days (LD). Under SD, this delayed-flowering phenotype was primarily
      due to the decreased expression of Oryza sativa GIGANTEA (OsGI), which controls
      three flowering activators: Heading date 1 (Hd1), OsMADS51, and Oryza sativa
      Indeterminate 1 (OsId1). Under LD, although the expression of several repressors,
      e.g., Hd1, Oryza sativa CONSTANS-like 4 (OsCOL4), and AP2 genes, was affected in
      the double mutant, that of Grain number, plant height and heading date 7 (Ghd7)
      was the most significantly reduced. These results indicated that OsPhyA
      influences flowering time mainly by affecting the expression of OsGI under SD and
      Ghd7 under LD when phytochrome B is absent. We also demonstrated that far-red
      light delays flowering time via both OsPhyA and OsPhyB. 

PMID- 27039185
TI  - A comparison between angiotensin converting enzyme inhibitors and angiotensin
      receptor blockers on end stage renal disease and major adverse cardiovascular
      events in diabetic patients: a population-based dynamic cohort study in Taiwan.
AB  - BACKGROUND: Contemporary guidelines recommend angiotensin-converting-enzyme
      inhibitors (ACEi) or angiotensin-receptor blockers (ARB) for hypertensive
      patients with diabetes. However, there is limited data to evaluate the comparison
      between ACEi and ARB on end stage renal disease (ESRD) and major adverse
      cardiovascular events (MACE), in Asian diabetic patients. METHODS: We used the
      Taiwan Longitudinal Cohort of Diabetes Patients Database to perform a population
      based dynamic cohort study. The comparison between ACEi and ARB on ESRD and MACE
      in diabetic patients was examined using the propensity score weighting method. We
      followed these patients until the occurrence of first study outcomes or end date
      of the study, whichever came first. RESULTS: There were 6898 and 12,758 patients
      in ACEi and ARB groups, respectively. The mean follow-up period was about 3.5
      years in ESRD and 2.5 years in MACE. The incidence of ESRD was 0.44 % and 0.63 %
      per person-years in the ACEi and ARB group, respectively. The risk of ESRD was
      lower in the ACEi group than the ARB group [hazard ratio (HR) 0.69; 95 %
      confidence interval (CI) 0.54-0.88, P = 0.0025]. Among those without chronic
      kidney disease (CKD), the incidence of ESRD was 0.30 % and 0.37 % per person
      years in the ACEi and ARB group, respectively. ACEi was similar to ARB in
      preventing ESRD for those without CKD (P = 0.11). Among those with CKD, the
      incidence of ESRD was 1.39 % and 2.34 % per person-years in the ACEi and ARB
      group, respectively. The ACEi group had a lower risk of ESRD than the ARB group
      (HR 0.61; 95 % CI 0.42-0.88, P = 0.008). The incidence of MACE was 9.33 % and
      9.62 % per person-years in the ACEi and ARB group, respectively. There was no
      significant difference in the composite MACE outcome between the two groups (P =
      0.42), but the ACEi group was associated with a higher risk of stroke than the
      ARB group (HR 1.12; 95 % CI 1.02-1.24, P = 0.02). CONCLUSIONS: ACEi compared with
      ARB was associated with a lower incidence of ESRD, especially in those with CKD.
      Though ACEi and ARB had a similar risk of composite MACE outcome, ACEi had a
      slightly higher incidence of stroke than ARB, among the Asian diabetic patients.

PMID- 27039186
TI  - Transarterial Radioembolization with Yttrium-90 for the Treatment of
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of worldwide
      mortality. Transarterial radioembolization (TARE) with yttrium-90 (Y90), a
      transcatheter intra-arterial procedure performed by interventional radiology, has
      become widely utilized in managing HCC. METHODS: The following is a focused
      review of TARE covering its commercially available products, clinical
      considerations of treatment, salient clinical trial data establishing its
      utility, and the current and future roles of TARE in the management of HCC.
      RESULTS: TARE is indicated for patients with unresectable, intermediate stage
      HCC. The two available products are glass and resin microspheres. All patients
      undergoing TARE must be assessed with a history, physical examination, clinical
      laboratory tests, imaging, and arteriography with macroaggregated albumin. TARE
      is safe and effective in the treatment of unresectable HCC, as it has a safer
      toxicity profile than chemoembolization, longer time-to-progression, greater
      ability to downsize and/or bridge patients to liver transplant, and utility in
      tumor complicated by portal vein thrombosis. TARE can also serve as an
      alternative to ablation and chemotherapy. CONCLUSION: TARE assumes an integral
      role in the management of unresectable HCC and has been validated by numerous
      studies.

PMID- 27039187
TI  - Molecular Cloning and Characterization of O-Methyltransferase from Mango Fruit
      (Mangifera indica cv. Alphonso).
AB  - Flavour of ripe Alphonso mango is invariably dominated by the de novo appearance
      of lactones and furanones during ripening. Of these, furanones comprising
      furaneol (4-hydroxy-2,5-dimethyl-3(2H)-furanone) and mesifuran (2,5-dimethyl-4
      methoxy-3(2H)-furanone) are of particular importance due to their sweet, fruity
      caramel-like flavour characters and low odour detection thresholds. We isolated a
      1056 bp complete open reading frame of a cDNA encoding S-adenosyl-L-methionine
      dependent O-methyltransferase from Alphonso mango. The recombinantly expressed
      enzyme, MiOMTS showed substrate specificity towards furaneol and protocatechuic
      aldehyde synthesizing mesifuran and vanillin, respectively, in an in vitro assay
      reaction. A semi-quantitative PCR analysis showed fruit-specific expression of
      MiOMTS transcripts. Quantitative real-time PCR displayed ripening-related
      expression pattern of MiOMTS in both pulp and skin of Alphonso mango. Also, early
      and significantly enhanced accumulation of its transcripts was detected in pulp
      and skin of ethylene-treated fruits. Ripening-related and fruit-specific
      expression profile of MiOMTS and substrate specificity towards furaneol is a
      suggestive of its involvement in the synthesis of mesifuran in Alphonso mango.
      Moreover, a significant trigger in the expression of MiOMTS transcripts in
      ethylene-treated fruits point towards the transcriptional regulation of mesifuran
      biosynthesis by ethylene. 

PMID- 27039188
TI  - Potentially inappropriate medication in the elderly in Germany: an economic
      appraisal of the PRISCUS list.
AB  - BACKGROUND: Several lists of potentially inappropriate medication (PIM) for
      elderly patients have been developed worldwide in recent years. Those lists
      intend to reduce prescriptions of drugs that carry an unnecessarily high risk of
      adverse drug events in elderly patients. In 2010, an expert panel published the
      PRISCUS list for the German drug market. This study calculates the amount of drug
      reimbursement for PIM in Germany and potential cost effects from the perspective
      of statutory health insurance when these are replaced by the substitutes
      recommended by the PRISCUS list. METHODS: Register-based data for the 30 top
      selling drugs on the PRISCUS list in 2009 for patients greater than or equal to
      65 years of age were provided by the Scientific Institute of the German Local
      Health Care Fund. We calculated the percentage of sales and defined daily doses
      for patients greater than or equal to 65 years of age compared with the total
      statutory health insurance population. Reimbursement costs for the recommended
      substitutions were estimated by considering different scenarios. RESULTS: In
      2009, drug reimbursement for the 30 top-selling PIM prescribed to patients
      greater than or equal to 65 years of age were calculated to be ?305.7 million.
      Prescribing the recommended substitution medication instead of PIM would lead to
      an increased total reimbursement cost for the German health care system ranging
      between from ?325.9 million to ?810.0 million. CONCLUSIONS: The results show that
      the substitution of PIM by medication deemed to be more appropriate for the
      elderly comes along with additional costs. Consequently, there is no short-term
      incentive for doing so from a payer perspective. Future studies have to consider
      the long-term effects and other sectors.

PMID- 27039189
TI  - Robotic surgery training: construct validity of Global Evaluative Assessment of
      Robotic Skills (GEARS).
AB  - The objective of this study is to determine the ability of the GEARS scale
      (Global Evaluative Assessment of Robotic Skills) to differentiate individuals
      with different levels of experience in robotic surgery, as a fundamental
      validation. This is a cross-sectional study that included three groups of
      individuals with different levels of experience in robotic surgery (expert,
      intermediate, novice) their performance were assessed by GEARS applied by two
      reviewers. The difference between groups was determined by Mann-Whitney test and
      the consistency between the reviewers was studied by Kendall W coefficient. The
      agreement between the reviewers of the scale GEARS was 0.96. The score was 29.8
      +/- 0.4 to experts, 24 +/- 2.8 to intermediates and 16 +/- 3 to novices, with a
      statistically significant difference between all of them (p < 0.05). All
      parameters from the scale allow discriminating between different levels of
      experience, with exception of the depth perception item. We conclude that the
      scale GEARS was able to differentiate between individuals with different levels
      of experience in robotic surgery and, therefore, is a validated and useful tool
      to evaluate surgeons in training. 

PMID- 27039190
TI  - Management of gallbladder duplication using a single-site robotic-assisted
      approach: a case study.
AB  - Gallbladder duplication is a rare congenital anomaly. Here, we describe a 29-year
      old female who presents with classic symptoms of biliary colic. A duplicated
      gallbladder was recognized on preoperative ultrasound. This case report reviews a
      single-site robotic-assisted cholecystectomy with a cystic duct duplication. The
      patient underwent the surgery without complication. Due to the aberrant anatomy
      of the cystic triangle, it was decided to mobilize the gallbladder in a dome-down
      fashion. True gallbladder duplication can be categorized according to cystic duct
      orientation based on Boyden's classification. Preoperative diagnosis is essential
      to prevent surgical complications. A laparoscopic approach can be carried out
      safely in the hands of a skilled surgeon. This case report shows that the robotic
      assisted surgical approach is a viable and safe alternative. 

PMID- 27039191
TI  - Robotic cystogastrostomy and debridement of walled-off pancreatic necrosis.
AB  - Walled-off pancreatic necrosis is a known complication of acute pancreatitis and
      requires intervention if symptomatic or complicated. Laparoscopic
      cystogastrostomy as a minimally invasive surgical intervention has been well
      described in surgical literature but data on a robotic approach is limited. Here
      we report a case of robotic cystogastrostomy and debridement of walled-off
      pancreatic necrosis in a patient with a history of severe biliary pancreatitis. 

PMID- 27039192
TI  - The role of the assistant during robot-assisted partial nephrectomy: does
      experience matter?
AB  - The objective of this study was to evaluate surgical outcomes with respect to the
      experience level of the bedside assistant during robot-assisted partial
      nephrectomy. A retrospective review was conducted of a prospectively maintained
      database of 414 consecutive robot-assisted laparoscopic partial nephrectomies
      performed by experienced robotic surgeons at our institution from April 2011 to
      September 2014. A senior-level assistant was defined as a resident in his or her
      post-graduate year (PGY) 4 or 5, or a fellow. Junior-level assistants were
      considered to be PGY-2, PGY-3, or a nurse first assistant. Multivariate analyses
      were performed using linear, Poisson, and logistic regression models. There were
      115 junior-level cases and 299 senior-level cases. On univariate analysis, the
      experience level of the assistant had no impact on operative time (168 for junior
      level vs. 163 min for senior level, p = 0.656). Likewise, there were no
      differences between the junior- and senior-level groups with regard to warm
      ischemia time (21.3 vs. 20.9 min, p = 0.843), negative margin status (111/115
      (96.5 %) vs. 280/299 (93.6 %), p = 0.340), or postoperative complications (17/115
      (14.8 %) vs. 35/299 (11.7 %), p = 0.408). After multivariate analysis, operative
      time was associated with increased body mass index and tumor size (both p <
      0.001), but not with resident experience level (p = 0.051). Estimated blood loss
      and postoperative complications were also not associated with the PGY of the
      assistant (p = 0.488 and p = 0.916, respectively). Despite common concern, the
      PGY status of a physician trainee serving as the bedside assistant does not
      appear to influence the outcomes of robot-assisted partial nephrectomy at a high
      volume center. 

PMID- 27039193
TI  - Microwave ablation of liver tumors: degree of tissue contraction as compared to
      RF ablation.
AB  - PURPOSE: To compare the amount of tissue contraction after microwave (MW) versus
      radiofrequency (RF) ablation of liver tumors. MATERIALS AND METHODS: Seventy-five
      hepatic tumors in 65 patients who underwent percutaneous MW or RF ablations were
      included in this retrospective study. All patients underwent MRI within 6 months
      before the ablation and 24 h after the procedure. Two blinded radiologists, by
      consensus, performed measurements on the corresponding series of pre and post
      ablation MRI. Absolute and relative contraction of liver, tumor, and control were
      calculated and compared. RESULTS: Thirty-one patients underwent MW ablations, and
      44 patients underwent RF ablations. The absolute and relative contraction of the
      ablation zone were significantly greater with MW than RF ablation (p = 0.003 to
      <0.001). Thirty-two lesions were visible on both pre- and post-ablation MRI. MW
      ablation had significantly more tumor contraction as compared to RF ablation (p =
      0.003 to 0.009). The control measurements demonstrated no significant difference
      in normal tissue variation between MW and RF groups. CONCLUSIONS: MW ablation of
      hepatic tumors produced significantly more contraction of tumor and ablated
      hepatic tissue compared to RF ablation. Tissue contraction should be taken into
      account during pre-procedural planning and assessing treatment response by
      comparing pre- and post-ablation images.

PMID- 27039194
TI  - Severe allergic-like contrast reactions: epidemiology and appropriate treatment.
AB  - Epinephrine is the most important treatment for severe allergic-like contrast
      reactions. The signs and symptoms of a severe reaction and the dose and methods
      of epinephrine administration are important for all radiologists to master. In
      this review article, we review the epidemiology of severe allergic-like contrast
      reactions, their common clinical manifestations, and their appropriate treatment,
      with a focus on correct epinephrine administration. We also discuss systematic
      limitations in the training of current and future radiologists, and recommend
      strategies for improvement.

PMID- 27039195
TI  - A Mixed-Methods Outcome Evaluation of a Mentorship Intervention for Canadian
      Nurses in HIV Care.
AB  - We assessed the impact of an HIV care mentorship intervention on knowledge,
      attitudes, and practices with nurses and people living with HIV (PLWH) in Canada.
      We implemented the intervention in two urban and two rural sites with 16 mentors
      (eight experienced HIV nurses and eight PLWH) and 40 mentees (nurses with limited
      HIV experience). The 6- to 12-month intervention included face-to-face workshops
      and monthly meetings. Using a mixed-methods approach, participants completed pre-
      and postintervention questionnaires and engaged in semistructured interviews at
      intervention initiation, mid-point, and completion. Data from 28 mentees (70%)
      and 14 mentors (87%) were included in the quantitative analysis. We analyzed
      questionnaire data using McNemar test, and interview data using content analysis.
      Results indicated positive changes in knowledge, attitudes, and practices among
      nurse mentees, with qualitative interviews highlighting mechanisms by which
      change occurred. Mentorship interventions have the potential to engage and
      educate nurses in HIV treatment and care.

PMID- 27039196
TI  - Gut Microbiotas and Host Evolution: Scaling Up Symbiosis.
AB  - Our understanding of species evolution is undergoing restructuring. It is well
      accepted that host-symbiont coevolution is responsible for fundamental aspects of
      biology. However, the emerging importance of plant- and animal-associated
      microbiotas to their hosts suggests a scale of coevolutionary interactions many
      fold greater than previously considered. This review builds on current
      understanding of symbionts and their contributions to host evolution to evaluate
      recent data demonstrating similar contributions of gut microbiotas. It further
      considers a multilayered model for microbiota to account for emerging themes in
      host-microbiota interactions. Drawing on the structure of bacterial genomes, this
      model distinguishes between a host-adapted core microbiota, and a flexible,
      environmentally modulated microbial pool, differing in constraints on their
      maintenance and in their contributions to host adaptation.

PMID- 27039197
TI  - ECG low QRS voltage and wide QRS complex predictive of centenarian 360-day
      mortality.
AB  - We examined the electrocardiographic (ECG) findings of centenarians and
      associated them with >360-day survival. Physical and functional assessment,
      resting electrocardiogram and laboratory tests were performed on 86 study
      participants 101.9 +/- 1.2 years old (mean +/- SD) (70 women, 16 men) and
      followed for at least 360 days. Centenarian ECGs were assessed for left
      ventricular hypertrophy (LVH) according to the Romhilt-Estes score, Sokolow-Lyon
      criteria and Cornell voltage criteria which were positive for 12.8, 6.98, and
      10.5 % of participants, respectively. Fifty-two study participants (60 %)
      survived >=360 days. Multivariate logistic regression analysis revealed a
      negative relationship between 360-day survival and the following: R II <0.45 mV
      adjusted for CRP (odds ratio (OR) = 0.108, 95 % confidence interval (CI) = 0.034
      0.341, P < .001), R aVF < 0.35 mV adjusted for CRP (OR = 0.151, 95 % CI = 0.039
      0.584, P < .006), Sokolow-Lyon voltage <1.45 mV adjusted for CRP (OR = 0.178, 95
      % CI = 0.064-0.492, P = .001), QRS >=90 ms adjusted for CRP (OR = 0.375, 95 % CI
      = 0.144-0.975, P = .044), and Romhilt-Estes score >=5 points adjusted for sex and
      Barthel Index (OR = 0.459, 95 % CI = 0.212-0.993, P = .048) in single variable
      ECG models. QRS voltage correlated positively with systolic and pulse pressure,
      serum vitamin B12 level, sodium, calcium, phosphorous, TIMP-1, and eGFR. QRS
      voltage correlated negatively with BMI, WHR, serum leptin, IL-6, TNF-alpha, and
      PAI-1 levels. QRS complex duration correlated positively with CRP; QTc correlated
      positively with TNF-alpha. Results suggest that Romhilt-Estes LVH criteria scores
      >=5 points, low ECG QRS voltages (Sokolow-Lyon voltage <1.45 mV), and QRS
      complexes >=90 ms are predictive of centenarian 360-day mortality. 

PMID- 27039199
TI  - Development of quantitative immunochromatographic kit and visual screening
      immunoassay strip for cadmium.
AB  - Cadmium is a highly toxic heavy metal for humans. In 2006, the Codex Alimentarius
      Commission set the international standard value of Cd contained in polished rice
      at 0.4 mg kg(-1), thus requiring the monitoring of Cd in food. We developed two
      types of Cd immunochromatographic kit by using anti-(Cd-EDTA) antibody. One is
      the quantitative Cd immunochromatographic device which can precisely measure Cd
      concentrations. The other is the Cd screening strip that enables visible
      evaluation of Cd exceeding 0.003 mg L(-1). Compared with conventional
      instrumental analysis methods, the immunoassay kits provide rapid, simple, and
      inexpensive on-site methods. For these kits, we also developed an efficient
      pretreatment method that can be easily administrated on-site. In this method,
      brown rice samples are coarsely crushed by a hand-held grinder then mixed with an
      enzyme solution, and Cd is extracted with HCl. The extracted solution is then
      purified by a newly developed Cd-selective ion exchange column. Cd concentrations
      measured by the quantitative Cd immunochromatographic devices correlated well
      with those obtained by ICP-OES (r (2) = 0.96). The Cd screening strips performed
      well in tests; pretreated purification solution which gave Cd concentrations
      exceeding 0.4 mg kg(-1) according to the Cd immunochromatographic devices gave
      corresponding results with the Cd screening strips with no false positives or
      false negatives. These results indicate that the two immunochromatographic kits
      are useful for on-site measurement of Cd concentrations and screening of Cd
      present in brown rice. 

PMID- 27039200
TI  - Multigrid MALDI mass spectrometry imaging (mMALDI MSI).
AB  - Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI)
      is an important technique for the spatially resolved molecular analysis of tissue
      sections. The selection of matrices influences the resulting mass spectra to a
      high degree. For extensive and simultaneous analysis, the application of
      different matrices to one tissue sample is desirable. To date, only a single
      matrix could be applied to a tissue section per experiment. However, repetitive
      removal of the matrix makes this approach time-consuming and damaging to tissue
      samples. To overcome these drawbacks, we developed a multigrid MALDI MSI
      technique (mMALDI MSI) that relies on automated inkjet printing to place
      differing matrices onto predefined dot grids. We used a cooled printhead to
      prevent cavitation of low viscosity solvents in the printhead nozzle. Improved
      spatial resolution of the dot grids was achieved by using a triple-pulse
      procedure that reduced droplet volume. The matrices can either be applied
      directly to the thaw-mounted tissue sample or by precoating the slide followed by
      mounting of the tissue sample. During the MALDI imaging process, we were able to
      precisely target different matrix point grids with the laser to simultaneously
      produce distinct mass spectra. Unlike the standard method, the prespotting
      approach optimizes the spectra quality, avoids analyte delocalization, and
      enables subsequent hematoxylin and eosin (H&E) staining. Graphical Abstract
      Scheme of the pre-spotted multigrid MALDI MSI workflow.

PMID- 27039198
TI  - Thyroid function and cardiovascular events in chronic kidney disease patients.
AB  - BACKGROUND AND AIMS: Abnormalities of thyroid function are commonly seen in
      chronic kidney disease (CKD) patients. They are associated with adverse clinical
      conditions such as atherosclerosis, endothelial dysfunction, inflammation and
      abnormal blood pressure variability. We investigated the association between
      thyroid disorders and endothelial function, assessed by flow-mediated dilatation
      (FMD) and carotid intima-media thickness (CIMT), and cardiovascular events (CVE)
      in CKD patients. MATERIALS AND METHODS: This observational cohort study included
      305 CKD (stages 1-5) patients. Routine biochemistry, including free T3, free T4
      and thyroid stimulating hormone, fibroblast growth factor-23 (FGF-23) and FMD,
      CIMT were measured. We divided patients into four groups according to thyroid
      hormone status: euthyroidism, subclinical hyperthyroidism, subclinical
      hypothyroidism, and euthyroid sick syndrome. Fatal and composite CVE were
      recorded for a median 29 months. RESULTS: Patients with subclinical
      hypothyroidism had a higher prevalence of hypertension and diabetes and also were
      more likely to have higher values of systolic CIMT, phosphorus, intact
      parathormone (iPTH), FGF-23, homeostasis model assessment-insulin resistance and
      lower levels of FMD than euthyroid patients. In the unadjusted survival analysis,
      subclinical hypothyroidism and euthyroid sick syndrome were associated with an
      increased risk for the outcome as compared with euthyroidism [hazard ratio 30.63
      (95 % confidence interval 12.27-76.48) and 12.17 (3.70-39.98), respectively]. The
      effects of subclinical hypothyroidism and euthyroid sick syndrome were maintained
      even in fully adjusted models. CONCLUSION: We demonstrated that subclinical
      hypothyroidism and euthyroid sick syndrome are associated with increased CVE in
      CKD patients. Further studies are needed to explore these issues.

PMID- 27039201
TI  - Development of a multi-class steroid hormone screening method using Liquid
      Chromatography/Tandem Mass Spectrometry (LC-MS/MS).
AB  - Monitoring complex endocrine pathways is often limited by indirect measurement or
      measurement of a single hormone class per analysis. There is a burgeoning need to
      develop specific direct-detection methods capable of providing simultaneous
      measurement of biologically relevant concentrations of multiple classes of
      hormones (estrogens, androgens, progestogens, and corticosteroids). The
      objectives of this study were to develop a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for multi-class steroid hormone detection using
      biologically relevant concentrations, then test limits of detection (LOD) in a
      high-background matrix by spiking charcoal-stripped fetal bovine serum (FBS)
      extract. Accuracy was tested with National Institute of Standards and Technology
      Standard Reference Materials (SRMs) with certified concentrations of cortisol,
      testosterone, and progesterone. 11-Deoxycorticosterone, 11-deoxycortisol, 17
      hydroxypregnenolone, 17-hydroxyprogesterone, adrenosterone, androstenedione,
      cortisol, corticosterone, dehydroepiandrosterone, dihydrotestosterone, estradiol,
      estriol, estrone, equilin, pregnenolone, progesterone, and testosterone were also
      measured using isotopic dilution. Dansyl chloride (DC) derivatization was
      investigated maintaining the same method to improve and expedite estrogen
      analysis. Biologically relevant LODs were determined for 15 hormones. DC
      derivatization improved estrogen response two- to eight-fold, and improved
      chromatographic separation. All measurements had an accuracy <=14 % difference
      from certified values (not accounting for uncertainty) and relative standard
      deviation <=14 %. This method chromatographically separated and quantified
      biologically relevant concentrations of four hormone classes using highly
      specific fragmentation patterns and measured certified values of hormones that
      were previously split into three separate chromatographic methods. 

PMID- 27039202
TI  - Microscopic imaging and tuning of electrogenerated chemiluminescence with boron
      doped diamond nanoelectrode arrays.
AB  - Nanoelectrode arrays (NEAs) are increasingly applied for a variety of
      electroanalytical applications; however, very few studies dealt with the use of
      NEAs as an electrochemical generator of electrogenerated chemiluminescence (ECL).
      In the present study, arrays of nanodisc and nanoband electrodes with different
      dimensions and inter-electrode distances were fabricated by e-beam lithography on
      a polycarbonate layer deposited on boron-doped diamond (BDD) substrates. In
      particular, NEAs with 16 different geometries were fabricated on the same BDD
      sample substrate obtaining a multiple nanoelectrode and ultramicroelectrode array
      platform (MNEAP). After electrochemical and morphological characterization, the
      MNEAP was used to capture simultaneously with a single image the characteristic
      behaviour of ECL emission from all the 16 arrays. Experiments were performed
      using Ru(bpy)3 (2+) as the ECL luminophore and tri-n-propylamine (TPrA) as the co
      reactant. With a relatively limited number of experiments, such an imaging
      procedure allowed to study the role that geometrical and mechanistic parameters
      play on ECL generation at NEAs. In particular, at high concentrations of TPrA,
      well-separated individual ECL spots or bands revealed an ECL signal which forms a
      pattern matching the nanofabricated structure. The analysis of the imaging data
      indicated that the thickness of the ECL-emitting zone at each nanoelectrode
      scales inversely with the co-reactant concentration, while significantly stronger
      ECL signals were detected for NEAs operating under overlap conditions. 

PMID- 27039203
TI  - On the role of experimental imperfections in constructing (1)H spin diffusion NMR
      plots for domain size measurements.
AB  - We discuss the precision of 1D chemical-shift-based (1)H spin diffusion NMR
      experiments as well as straightforward experimental protocols for reducing
      errors. The (1)H spin diffusion NMR experiments described herein are useful for
      samples that contain components with significant spectral overlap in the (1)H NMR
      spectrum and also for samples of small mass (<1mg). We show that even in samples
      that display little spectral contrast, domain sizes can be determined to a
      relatively high degree of certainty if common experimental variability is
      accounted for and known. In particular, one should (1) measure flip angles to
      high precision (~+/-1 degrees  flip angle), (2) establish a metric for phase
      transients to ensure their repeatability, (3) establish a reliable spectral
      deconvolution procedure to ascertain the deconvolved spectra of the neat
      components in the composite or blend spin diffusion spectrum, and (4) when
      possible, perform 1D chemical-shift-based (1)H spin diffusion experiments with
      zero total integral to partially correct for errors and uncertainties if these
      requirements cannot fully be implemented. We show that minimizing the degree of
      phase transients is not a requirement for reliable domain size measurement, but
      their repeatability is essential, as is knowing their contribution to the
      spectral offset (i.e. the J1 coefficient). When performing experiments with zero
      total integral in the spin diffusion NMR spectrum with carefully measured flip
      angles and known phase transient effects, the largest contribution to error
      arises from an uncertainty in the component lineshapes which can be as high as
      7%. This uncertainty can be reduced considerably if the component lineshapes
      deconvolved from the composite or blend spin diffusion spectra adequately match
      previously acquired pure component spectra.

PMID- 27039204
TI  - Psychometric assessment of the Chinese version of the MASCC Antiemesis Tool (MAT)
      for measuring chemotherapy-induced nausea and vomiting.
AB  - PURPOSE: This paper aims to assess the psychometric properties of the Chinese
      version of the MASCC Antiemesis Tool (MAT) for measuring chemotherapy-induced
      nausea and vomiting (CINV). METHODS: This was a psychometric study using a panel
      of experts and a prospective observational design. Six experts were invited to
      identify the content validity and face validity of the MAT, and 115 cancer
      patients were then recruited from three provincial medical centers in Fuzhou,
      China. The MAT was self-completed by the patients on the first and the fifth day
      after receiving the most recent chemotherapy, and patients also rated daily the
      Index of Nausea, Vomiting, and Retching (INVR) during the first 5 days after
      chemotherapy. Content validity was measured by the index of the content validity
      (CVI). Construct validity was estimated by the contrasted groups approach.
      Concurrent validity was measured by exploring the correlations between the INVR
      and MAT scores. The reliability of the MAT was examined by Cronbach's alpha and
      item-to-total correlations. RESULTS: One hundred and eleven subjects returned the
      completed measures. High content validity was determined. Contrasted groups
      analysis clearly discriminated the differences on the CINV symptom experiences
      between different age and gender groups. Excellent concurrent validity was
      identified, with the Spearman's correlation coefficient between the MAT total
      score and the INVR overall total score of 0.94 (P < 0.001). Cronbach's alpha for
      the MAT was 0.73, and the item-to-total correlations ranged from 0.50 to 0.71.
      CONCLUSIONS: The MAT Chinese version is a valid, reliable, and convenient
      instrument for measuring CINV in Chinese cancer patients.

PMID- 27039205
TI  - "Enjoy glass of wine before eating:" a randomized trial to test the orexigenic
      effects of this advice in advanced cancer patients.
AB  - BACKGROUND: Because the extant literature suggests wine increases appetite, this
      study sought to determine whether this effect could be observed in advanced
      cancer patients with appetite loss. METHODS: Advanced cancer patients with self
      reported loss of appetite were randomly assigned to white wine with <=15 %
      alcohol content twice a day for 3-4 weeks versus a nutritional supplement, such
      as Boost(r) or Ensure(r). Patients assigned to wine were encouraged to also take
      a nutritional supplement, whereas patients assigned to the nutritional supplement
      arm were told to abstain completely from alcohol. Patient-reported outcomes were
      captured with a validated questionnaire to assess the primary endpoint of
      appetite improvement. RESULTS: A total of 141 patients (118 evaluable) were
      enrolled. Twenty-eight patients (48 %) in the wine arm reported an improvement in
      appetite at some point during the treatment period, whereas 22 patients (37 %)
      assigned to the nutritional supplement arm also reported improvement (p = 0.35).
      Other appetite-related questions and questionnaire items showed no statistically
      significant differences between treatment arms. In both arms, approximately 9 %
      of patients achieved weight stability (p = 0.98); median survival was not
      statistically different. Both interventions were well tolerated. CONCLUSION: As
      prescribed in this trial, wine does not improve appetite or weight in advanced
      cancer patients.

PMID- 27039206
TI  - Breast cancer survivors suffer from persistent postmastectomy pain syndrome and
      posttraumatic stress disorder (ORTHUS study): a study of the palliative care
      working committee of the Turkish Oncology Group (TOG).
AB  - PURPOSE: Persistent postmastectomy pain syndrome (PMPS) is one of the most
      important disturbing symptoms. Posttraumatic stress disorder (PTSD) is an anxiety
      disorder which is characterized by reactions to reminders of the trauma that has
      been experienced. The purpose of this study is to evaluate the predictors of PMPS
      and PTSD in Turkish breast cancer survivors and the correlation between PMPS and
      PTSD. METHOD: The study is designed as a multicenter survey study. Breast cancer
      patients in remission were evaluated. Patients were evaluated with structured
      questionnaires to assess the PMPS and clinical parameters associated with it. The
      Turkish version of the posttraumatic stress disorder checklist-civilian version
      (PCL-C) was used. RESULTS: Between February 2015 and October 2015, 614 breast
      cancer survivors in outpatient clinics were evaluated. The incidence of PMPS
      documented is 45.1 %. In the multivariate analysis low income, presence of PTSD
      and <46 months after surgery were associated with increased risk of PMPS. PTSD
      was documented in 75 %, and the mean PCL-C score was 32.4 +/- 11.1. PMPS and
      being married at the time of the evaluation were linked with PTSD. CONCLUSIONS:
      It is the first data about the association between PMPS and PTSD. The clinicians
      should be aware of PMPS and PTSD in breast cancer survivors.

PMID- 27039207
TI  - Appraisals, perceived dyadic communication, and quality of life over time among
      couples coping with prostate cancer.
AB  - PURPOSE: Little research has examined how prostate cancer patients' and their
      spouses' appraisals of illness and quality of life (QOL) interact with one
      another. This study examined the interdependent relationships between their
      appraisals of illness and QOL and if their perceived dyadic communication
      mediated these relationships. METHODS: We used the Actor-Partner Interdependence
      Mediation Model (APIMeM) approach to conduct a secondary analysis of longitudinal
      data from 124 prostate cancer patient-spouse dyads. We examined actor effects
      (each person's influence on his/her own outcomes) and partner effects (each
      person's influence on his/her partner's outcomes). Appraisals of illness,
      perceived dyadic communication, and QOL were measured using Appraisal of Illness
      Scale, Lewis Mutuality and Interpersonal Sensitivity Scale, and Functional
      Assessment of Chronic Illness Therapy General Scale, respectively. Analyses
      controlled for effects of prostate cancer symptoms and demographic factors.
      RESULTS: Among actor effects, spouses with more negative appraisals at baseline
      perceived worse dyadic communication 4 months later (p < .05) and worse QOL 8
      months later (p < .001). Patients and spouses who perceived more dyadic
      communication at 4 months had better QOL at 8 months (p < .01). Among partner
      effects, there was only weak evidence for an association between patient
      perceived dyadic communication at 4 months and better spouse QOL at 8 months of
      follow-up (p = .05). No mediation effects were found. CONCLUSIONS: Patients' and
      spouses' appraisals of the illness and their dyadic communication were associated
      with their long-term QOL. Interventions that reduce negative appraisals of
      illness and promote dyadic communication may improve QOL for both patients with
      prostate cancer and their spouses.

PMID- 27039208
TI  - Sulforaphane regulates phenotypic and functional switching of both induced and
      spontaneously differentiating human monocytes.
AB  - At the site of inflammation, switching default on polarization of monocyte
      differentiation into classically activated macrophages (M1 type) is one of the
      pathogenic outcomes in several inflammatory autoimmune diseases, such as
      rheumatoid arthritis and osteoarthritis. In rheumatoid and osteoarthritis, a
      soluble collagen known as self-antigen is considered as a biomarker and acts as
      an important inflammatory mediator. In the present study, we investigated the
      effects of sulforaphane (SFN) on phenotypic changes and functional switching
      during in vitro induced and spontaneous differentiation of monocytes/macrophages,
      whose conditions were established with THP1 induced by PMA, and human peripheral
      blood monocytes, respectively. SFN at non-cytotoxic concentration (10MUM) blocked
      soluble collagen induced inflammatory responses specific to M1 macrophages, COX
      2, iNOS, surface CD14, CD197 expressions and production of IL12p70, suggesting
      that signals induced by SFN eventually shifted macrophage polarization to a
      direction specific to M2 macrophages (CD36high CD197extremely low). Results
      obtained with the induction of inflammatory conditions specific to M1 macrophages
      followed by SFN treatment showed that MAPKs were involved in the M1 to M2
      phenotype switching. This immune-modulatory nature of SFN provides a clear
      indication for its ability to alleviate chronic inflammatory diseases by
      targeting monocytes/macrophages. 

PMID- 27039209
TI  - RETRACTED: Sophocarpine displays anti-inflammatory effect via inhibiting TLR4 and
      TLR4 downstream pathways on LPS-induced mastitis in the mammary gland of mice.
AB  - Mastitis is defined as the inflammation of the mammary gland. LPS, which is
      widely used to induce mastitis models for the study of this disease, triggers
      similar inflammation as Escherichia coli. Sophocarpine, isolated from Sophora
      alopecuroides L., exhibits multiple biological properties. The aim of the present
      study was to determine the anti-inflammatory effect and mechanism of action of
      sophocarpine on mastitis within an LPS-induced mouse model. ELISA and western
      blotting were performed to detect protein levels. The qPCR was performed to
      detect mRNA levels. The ELISA and qRT-PCR results showed that sophocarpine
      inhibited the expression of TNF-alpha, IL-1beta and IL-6 in a dose-dependent
      manner. However, sophocarpine suppressed TLR4 expression. Further study showed
      that sophocarpine could suppress the phosphorylation of IkappaBalpha, p65 and
      p38. These results confirm that sophocarpine played an anti-inflammatory role in
      LPS-induced mastitis by regulating TLR4 and the NF-kappaB and MAPK signaling
      pathways in mammary gland tissues. Therefore, sophocarpine may be a potential
      therapeutic drug for the treatment of mastitis.

PMID- 27039210
TI  - Baicalin ameliorates experimental inflammatory bowel disease through polarization
      of macrophages to an M2 phenotype.
AB  - Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the
      intestinal tract. Baicalin, originally isolated from the root of the Chinese herb
      Huangqin (Scutellaria baicalensis Georgi) and its main active ingredient, has a
      protective effect against inflammatory responses in several diseases. The present
      study investigated the effects of baicalin on macrophage polarization and its
      therapeutic role in IBD. Murine peritoneal macrophages and mice with colitis were
      treated with baicalin. Macrophage subset distribution, M1 and M2 macrophage
      associated mRNA expression, and interferon regulatory factor 4 and 5 (IRF4 and
      IRF5) expression were analyzed. siRNA transfection into mouse peritoneal
      macrophages was utilized to suppress IRF4. Fluorescence-activated cell sorting,
      western blot, and real-time PCR analyses were performed. Baicalin (50MUM) limited
      lipopolysaccharide (LPS)-induced M1 macrophage polarization; decreased LPS
      induced tumor necrosis factor alpha, interleukin (IL)-23, and IRF5 expression;
      and increased IL-10, arginase-1 (Arg-1), and IRF4 expression. siRNA-mediated IRF4
      silencing significantly impaired baicalin activity. Furthermore, pretreatment
      with baicalin (100mg/kg) in mice with dextran sodium sulfate (DSS)-induced
      colitis ameliorated the severity of colitis and significantly decreased the
      disease activity index (baicalin group, 3.33+/-0.52 vs. DSS group, 5.67+/-1.03).
      Baicalin (100mg/kg) also repressed IRF5 protein expression and promoted IRF4
      protein expression in the lamina propria mononuclear cells, and induced
      macrophage polarization to the M2 phenotype. In summary, our results showed that
      baicalin upregulates IRF4 protein expression and reverses LPS-induced macrophage
      subset redistribution. Thus, baicalin alleviates DSS-induced colitis by
      modulating macrophage polarization to the M2 phenotype. 

PMID- 27039211
TI  - Aqueous leaf extract of Passiflora alata Curtis promotes antioxidant and anti
      inflammatory effects and consequently preservation of NOD mice beta cells (non
      obese diabetic).
AB  - Passiflora alata Curtis (P. alata) leaves have anti-inflammatory properties; the
      present study aimed to investigate the anti-diabetogenic properties of P. alata
      aqueous leaf extract. HPLC analysis identified the phenolic compounds catechin,
      epicatechin and rutin. The aqueous extract was administered for 30weeks to non
      obese diabetic (NOD) mice presenting a decrease of 28.6% in diabetes incidence
      and the number of inflammatory cells in pancreatic islets, when compared with the
      control group (water). The P. alata group presented an antioxidant effect and
      decreased lipid peroxidation in the serum of NOD mice. Increased numbers of
      insulin-positive cells were also observed in the pancreatic islets of the treated
      group. The diabetic group exhibited higher levels in the glucose tolerance test
      and glycemic index, in comparison to the P. alata-treated group and non-diabetic
      control BALB/c mice. In addition, the P. alata extract reduced the percentage and
      the proliferation index of NOD mice lymphocytes submitted to in vitro
      dose/response mitogenic stimulation assays. These results suggest that the
      aqueous extract of P. alata has anti-inflammatory properties, contributing to the
      protection of beta cells in pancreatic islets in NOD mice, and presents potential
      for use a supporting approach to treat type 1 diabetes. 

PMID- 27039212
TI  - Optimization of a methamphetamine conjugate vaccine for antibody production in
      mice.
AB  - There are still no approved medications for treating patients who abuse
      methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are
      in clinical studies, but have not proven effective seemingly due to inadequate
      anti-drug antibody production. The current studies aimed to optimize the
      composition, adjuvant and route of administration of a methamphetamine conjugate
      vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher
      antibody levels. A range of hapten epitope densities were compared, as were the
      adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE.
      While methamphetamine hapten density did not strongly affect the antibody
      response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water
      emulsion (GLA-SE) produced much higher levels of antibody in response to
      immunization compared with Alhydrogel; immunization with GLA-SE also produced
      antibodies with higher affinities for methamphetamine. GLA-SE has been used in
      human studies of vaccines for influenza among others and like some other clinical
      TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted
      vaccines are typically administered by intramuscular injection and this also
      proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9
      methamphetamine vaccine adjuvanted with GLA-SE have the potential for
      demonstrating efficacy by generating much higher levels of antibody than
      substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. 

PMID- 27039213
TI  - Radiographic Analysis of the Hill-Sachs Lesion in Anteroinferior Shoulder
      Instability After First-Time Dislocations.
AB  - PURPOSE: To identify the relation between the Hill-Sachs (H-S) angle and arm
      position at the time of the initial dislocation, and to see if this correlates
      with the glenoid track. METHODS: A total of 102 patients (89 male patients,
      87.2%), with a mean age of 32 years (range, 17 to 38 years), were divided into 2
      groups, abduction (ABD) and adduction (ADD), dependent on the position of the arm
      at the time of the instability event. All patients were evaluated with bilateral
      computed tomography scans (3-dimensional) to define the H-S position on the
      glenoid track and to measure the H-S angle. One-way analysis of variance was used
      to compare the H-S angle between the 2 groups. RESULTS: Dislocation occurred in
      ABD in 45 patients (44.1%) and in ADD in 57 (55.9%). The H-S angle was 32.4
      degrees  +/- 4.7 degrees  in the ABD group versus 16.1 degrees  +/- 2.9 degrees 
      in the ADD group. All patients' injuries were "on-track" glenoid injuries in both
      groups. CONCLUSIONS: This study identified a difference in the H-S angle relative
      to arm position at the time of initial dislocation. Patients whose injury
      occurred in the ABD position showed a higher H-S angle, leading to an increased
      risk of engagement, because the long axis of the H-S lesion is parallel to the
      glenoid in a position of function. Thus arm position at the time of the initial
      instability event may be a risk factor for engagement and higher risk of
      recurrence. LEVEL OF EVIDENCE: Level IV, prognostic case series.

PMID- 27039214
TI  - The Incidence of Subsequent Surgery After Outpatient Arthroscopic Rotator Cuff
      Repair.
AB  - PURPOSE: To quantify the incidence and risk factors associated with subsequent
      shoulder procedures in individuals undergoing outpatient arthroscopic rotator
      cuff repair (ARCR). METHODS: We examined the New York Statewide Planning and
      Research Cooperative Systems outpatient database from 2003 through 2014 to
      identify patients undergoing isolated ARCR with or without concomitant
      acromioplasty. Patients were longitudinally followed up for a minimum of 2 years
      to determine the incidence of subsequent ipsilateral shoulder surgery. The impact
      of age, sex, insurance, concomitant acromioplasty, and tobacco use on reoperation
      was explored. RESULTS: Between 2003 and 2012, 30,430 patients underwent isolated
      ARCR. The mean age was 56.6 +/- 11.5 years, and 55.1% were male patients. A total
      of 1,826 patients (6.0%) underwent subsequent ipsilateral outpatient shoulder
      surgery a mean of 24.3 +/- 27.1 months after the initial ARCR. Of patients who
      underwent repeat surgery, 57.3% underwent a revision cuff repair. Patients who
      underwent additional outpatient shoulder surgery were significantly younger (53.7
      +/- 10.9 years v 56.8 +/- 11.5 years, P < .001). Tobacco use was associated with
      an increased rate of subsequent surgery (7.3% v 5.9%, P = .044) and accelerated
      time to reoperation (16.9 months v 24.7 months, P < .001). Independent risk
      factors for subsequent ipsilateral surgery after initial ARCR were presence of a
      Workers' Compensation claim (odds ratio, 2.11; 95% confidence interval, 1.89
      2.36; P < .001) and initial ARCR without acromioplasty (odds ratio, 1.20; 95%
      confidence interval, 1.09-1.34; P < .001). CONCLUSIONS: We identified a 6.0%
      incidence of repeat ipsilateral surgery after isolated ARCR. Although reasons for
      reoperation are likely multifactorial, younger age, Workers' Compensation claim,
      and absence of acromioplasty at the time of initial ARCR remained independent
      predictors of subsequent outpatient procedures, whereas a history of tobacco use
      was associated with accelerated time to subsequent surgery. LEVEL OF EVIDENCE:
      Level III, retrospective comparative study.

PMID- 27039215
TI  - Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones
      as a general cellular response to stress.
AB  - Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia
      magna. Previous results characterized gene transcripts of genes encoding and
      efflux activities of four putative ABCB1 and ABCC transporters that were
      chemically induced but showed low specificity against model transporter
      substrates and inhibitors, thus preventing us from distinguishing between
      activities of different efflux transporter types. In this study we report on the
      specificity of induction of ABC transporters and of the stress protein hsp70 in
      clones selected to be genetically resistant to ABCB1 chemical substrates. Clones
      resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive
      transcriptional responses of transporter protein coding genes and of putative
      transporter dye activities. Expression of hsp70 proteins also varied across
      resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed
      high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene
      transporter and of putative dye transporter activity were also induced to a
      greater extent in the pentachlorophenol resistant clone. Observed higher dye
      transporter activities in individuals from clones resistant to mitoxantrone and
      ivermectin were unrelated with transcriptional levels of the studied four abcc
      and abcb1 transporter genes. These findings suggest that Abcb1 induction in D.
      magna may be a part of a general cellular stress response. 

PMID- 27039216
TI  - Identification and characterization of the melanoma differentiation - associated
      gene 5 in sea perch, Lateolabrax japonicus.
AB  - The RIG-I-like receptors family is a group of cytosolic RNA helicase proteins
      that can recognize viral RNA via binding to pathogen associated molecular pattern
      motifs within RNA ligands. A novel vertebrate RLR counterpart named LjMDA5 was
      firstly identified from the marine fish sea perch Lateolabrax japonicus in this
      study. The full-length cDNA of LjMDA5 is 3750 bp and encodes a polypeptide of 988
      amino acids, containing two N-terminal tandem caspase activation and recruitment
      domains, a DExH (Asp-Glu-X-His) box domain, an HELICc domain, and a C-terminal
      domain RIG-I. Phylogenetic analysis showed that LjMDA5 shared the closest genetic
      relationship with the MDA5 of Larimichthys crocea. Quantitative RT-PCR analysis
      showed that LjMDA5 was ubiquitously expressed and up-regulated significantly in
      all selected tissues in vivo post NNV infection. Time course analysis showed that
      LjMDA5 transcripts significantly increased in spleen and kidney. We found LjMDA5
      could be regulated in the sea perch LJB and LJF cell lines after
      lipopolysaccharide, polyinosinic-polycytidylic acid treatment and NNV challenge.
      RNA interference experiment indicated that silencing of LjMDA5 significantly
      increased RGNNV replication and virus production in NNV infected LJF cells. Our
      results revealed that MDA5 was essential for host defense against NNV, which
      provided new insights into the function of RLR signaling pathway during NNV
      infection in fish.

PMID- 27039217
TI  - Incidentalomas associated with abdominal and pelvic CT angiograms for abdominal
      based breast free flap reconstruction.
AB  - Computed tomography angiography (CTA) is routinely performed prior to breast
      reconstruction using deep inferior epigastric perforator (DIEP) flaps to provide
      better surgical planning and improve preoperative decision making. These
      investigations occasionally result in unexpected findings in otherwise
      asymptomatic women. Unexpected findings on imaging in a population of women with
      previous breast cancer or strong breast cancer risk factors can lead to undue
      stress and anxiety. The aim of this study is to determine the incidence of
      unexpected findings in preoperative CT angiograms and to correlate these with
      patient and breast cancer characteristics. A retrospective chart review from May
      2008 to December 2012 was performed reviewing all patients who underwent DIEP
      flap breast reconstruction. Radiology reports of their preoperative CT
      angiograms, details of unexpected findings, patients' past medical and cancer
      history, additional radiological investigations, outcomes, and interventions were
      reviewed. In total, 360 patients met the inclusion criteria for the study. Sixty
      four percent of the patients who underwent CTA imaging had incidental findings.
      Further imaging was suggested in 48% of this group. The most common
      incidentalomas were hepatic (47%), bone (24%), and renal (20%). "Incidentalomas"
      were associated with patients' underlying comorbidities (p = 0.001) and age (p =
      0.01). "Radiographically suspicious incidentalomas" were associated with the
      underlying comorbidities (p = 0.001). The radiologists most commonly suggested
      investigation methods such as ultrasound (41%), another CT (28%), bone scan
      (21%), and magnetic resonance imaging (MRI; 14%). No incidentalomas were found to
      be malignant on further recommended investigation in this study and no breast
      cancer reconstruction was delayed as a result of the discovery of incidentalomas
      or their subsequent investigations. It is important to counsel patients of the
      possibility of incidental findings and the resulting sequelae prior to CTA
      investigations for breast cancer reconstruction and involve them in shared
      decision making if additional investigations are required. 

PMID- 27039218
TI  - Extracorporeally frozen tumour-bearing bone combined with free vascularised
      fibula for the intercalary reconstruction of femoral defect after resection of
      bony sarcoma.
AB  - BACKGROUND: With the improved survival for patients with bone sarcomas, there is
      a trend to reconstruct intercalary femur defects using biologic techniques. This
      study examined whether the results of a frozen femur autograft with vascularised
      fibula are comparable to other reconstructive options in terms of the functional
      outcomes and the complications. MATERIALS AND METHODS: Between 2008 and 2012,
      eight patients with bony sarcoma of the femur were subjected to reconstruction
      with a recycled frozen autograft combined with a vascularised fibula flap inside.
      The oncologic and functional results were analysed retrospectively. RESULTS: The
      mean follow-up was 48.7 months (37-71). The oncologic results were continuously
      disease free in five patients; there was no evidence of disease in one, one
      patient was alive with disease and another died of the disease. The average
      length of defect was 13.6 cm (9-21). Bone union was achieved in all cases. The
      mean time to bone union was 7.9 months (5-19) and to full weight bearing was 7.8
      months (6-11). There was no infection or construct fracture in this series. Two
      complications were observed. One tumour recurrence in soft tissue was treated
      with reresection. One tibia fracture was successfully managed with cast
      immobilisation. The average Musculoskeletal Tumor Society functional score was
      95% (27-30). The construct was intact in all patients. CONCLUSIONS: Vascularised
      fibular flap combined with frozen autografts is a dependable and durable option
      for the reconstruction of large bony defects after femoral sarcoma resection. It
      had the merits of reliable bone union and low complications, which compare well
      with other biological reconstructions. Evidence Rating Scale for Therapeutic
      Studies Level IV, therapeutic study.

PMID- 27039219
TI  - Use of a purified collagen membrane to aid closure of palatal fistulae.
AB  - INTRODUCTION: Fistula formation following closure of palatal clefts remains a
      difficult clinical complication. A significant recurrence rate has also been
      reported following attempted closure. We present our results of fistula closure
      augmented with Bio-Gide((r)), a purified porcine collagen membrane designed to
      promote guided tissue regeneration. METHODS: We reviewed the records of 263
      patients operated between 1993 and 2011 for closure of palatal fistula. The
      patients selected comprised 61 who underwent fistula closure augmented with Bio
      Gide and 202 with other techniques in the absence of Bio-Gide. We reviewed the
      age at surgery, sex, location of fistula, cleft type and outcome. Operation
      success was defined as an asymptomatic patient along with visible confirmation of
      closure of the fistula. RESULTS: The overall fistula closure rate was 75% in the
      Bio-Gide group and 63% in the non-Bio-Gide group (p = 0.070) and 86% versus 61%
      in the unilateral cleft palate patients (p = 0.027). DISCUSSION: Bio-Gide has
      improved the success rate in fistula closure in this study. Using this technique,
      fistula closure can be performed as a day case procedure and does not need to
      transgress any original suture lines; an additional advantage is that this
      procedure does not require harvesting of any autologous tissue to augment the
      repair.

PMID- 27039220
TI  - Targeted drug delivery to ischemic stroke via chlorotoxin-anchored, lexiscan
      loaded nanoparticles.
AB  - Ischemic stroke is a leading cause of disability and death worldwide. Current
      drug treatment for stroke remains inadequate due to the existence of the blood
      brain barrier. We proposed an innovative nanotechnology-based autocatalytic
      targeting approach, in which the blood-brain barrier modulator lexiscan is
      encapsulated in nanoparticles to enhance blood-brain barrier permeability and
      autocatalytically augment the brain stroke-targeting delivery efficiency of
      chlorotoxin-anchored nanoparticles. The nanoparticles efficiently and
      specifically accumulated in the brain ischemic microenvironment and the targeting
      efficiency autocatalytically increased with subsequent administrations. When Nogo
      66 receptor antagonist peptide NEP1-40, a potential therapeutic agent for
      ischemic stroke, was loaded, nanoparticles significantly reduced infarct volumes
      and enhanced survival. Our findings suggest that the autocatalytic targeting
      approach is a promising strategy for drug delivery to the ischemic
      microenvironment inside the brain. Nanoparticles developed in this study may
      serve as a new approach for the clinical management of stroke.

PMID- 27039221
TI  - Three-Dimensional Quantitative Validation of Breast Magnetic Resonance Imaging
      Background Parenchymal Enhancement Assessments.
AB  - The magnetic resonance imaging (MRI) background parenchymal enhancement (BPE) and
      its clinical significance as a biomarker of breast cancer risk has been proposed
      based on qualitative studies. Previous BPE quantification studies lack
      appropriate correlation with BPE qualitative assessments. The purpose of this
      study is to validate our three-dimensional BPE quantification method with
      standardized BPE qualitative cases. An Institutional Review Board-approved study
      reviewed 500 consecutive magnetic resonance imaging cases (from January 2013
      December 2014) using a strict inclusion criteria and 120 cases that best
      represented each of the BPE qualitative categories (minimal or mild or moderate
      or marked) were selected. Blinded to the qualitative data, fibroglandular tissue
      contours of precontrast and postcontrast images were delineated using an in
      house, proprietary segmentation algorithm. Metrics of BPE were calculated
      including %BPE ([ratio of BPE volume to fibroglandular tissue volume] * 100) at
      multiple threshold levels to determine the optimal cutoff point for BPE
      quantification that best correlated with the reference BPE qualitative cases. The
      highest positive correlation was present at *1.5 precontrast average signal
      intensity threshold level (r = 0.84, P < 0.001). At this level, the BPE
      qualitative assessment of minimal, mild, moderate, and marked correlated with the
      mean quantitative %BPE of 14.1% (95% CI: 10.9-17.2), 26.1% (95% CI: 22.8-29.3),
      45.9% (95% CI: 40.2-51.7), and 74.0% (95% CI: 68.6-79.5), respectively. A one-way
      analysis of variance with post-hoc analysis showed that at *1.5 precontrast
      average signal intensity level, the quantitative %BPE measurements best
      differentiated the four reference BPE qualitative groups (F [3,117] = 106.8, P <
      0.001). Our three-dimensional BPE quantification methodology was validated using
      the reference BPE qualitative cases and could become an invaluable clinical tool
      to more accurately assess breast cancer risk and to test chemoprevention
      strategies. 

PMID- 27039222
TI  - Craniofacial and upper airway morphology in adult obstructive sleep apnea
      patients: A systematic review and meta-analysis of cephalometric studies.
AB  - Obstructive sleep apnea (OSA) is one of the common sleep breathing disorders in
      adults, characterised by frequent episodes of upper airway collapse during sleep.
      Craniofacial disharmony is an important risk factor for OSA. Overnight
      polysomnography (PSG) study is considered to be the most reliable confirmatory
      investigation for OSA diagnosis, whereas the precise localization of site of
      obstruction to the airflow cannot be detected. Identifying the cause of OSA in a
      particular ethnic population/individual subject helps to understand the
      etiological factors and effective management of OSA. The objective of the meta
      analysis is to elucidate altered craniofacial anatomy on lateral cephalograms in
      adult subjects with established OSA. Significant weighted mean difference with
      insignificant heterogeneity was found for the following parameters: anterior
      lower facial height (ALFH: 2.48 mm), position of hyoid bone (Go-H: 5.45 mm, S-H:
      6.89 mm, GoGn-H: 11.84 degrees , GoGn-H: 7.22 mm, N-S-H: 2.14 degrees ), and
      pharyngeal airway space (PNS-Phw: -1.55 mm, pharyngeal space: -495.74 mm2 and oro
      pharyngeal area: -151.15 mm2). Significant weighted mean difference with
      significant heterogeneity was found for the following parameters: cranial base
      (SN: -2.25 mm, S-N-Ba: -1.45 degrees ), position and length of mandible (SNB: 
      1.49 degrees  and Go-Me: -5.66 mm) respectively, maxillary length (ANS-PNS: -1.76
      mm), tongue area (T: 366.51 mm2), soft palate area (UV: 125.02 mm2), and upper
      airway length (UAL: 5.39 mm). This meta-analysis supports the relationship
      between craniofacial disharmony and obstructive sleep apnea. There is a strong
      evidence for reduced pharyngeal airway space, inferiorly placed hyoid bone and
      increased anterior facial heights in adult OSA patients compared to control
      subjects. The cephalometric analysis provides insight into anatomical basis of
      the etiology of OSA that can influence making a choice of appropriate therapy.

PMID- 27039223
TI  - Effects of sleep manipulation on cognitive functioning of adolescents: A
      systematic review.
AB  - Adolescents are considered to be at risk for deteriorated cognitive functioning
      due to insufficient sleep. This systematic review examined the effects of
      experimental sleep manipulation on adolescent cognitive functioning. Sleep
      manipulations consisted of total or partial sleep restriction, sleep extension,
      and sleep improvement. Only articles written in English, with participants' mean
      age between 10 and 19 y, using objective sleep measures and cognitive performance
      as outcomes were included. Based on these criteria 16 articles were included. The
      results showed that the sleep manipulations were successful. Partial sleep
      restriction had small or no effects on adolescent cognitive functioning. Sleep
      deprivation studies showed decrements in the psychomotor vigilance task as most
      consistent finding. Sleep extension and sleep improvement contributed to
      improvement of working memory. Sleep directly after learning improved memory
      consolidation. Due to the great diversity of tests and lack of coherent results,
      decisive conclusions could not be drawn about which domains in particular were
      influenced by sleep manipulation. Small number of participants, not accounting
      for the role of sleep quality, individual differences in sleep need, compensatory
      mechanisms in adolescent sleep and cognitive functioning, and the impurity
      problem of cognitive tests might explain the absence of more distinct results.

PMID- 27039224
TI  - Comparison of Controlled Attenuation Parameter and Liver Biopsy to Assess Hepatic
      Steatosis in Pediatric Patients.
AB  - OBJECTIVE: To assess whether the degree of steatosis as determined by controlled
      attenuation parameter (CAP) measurements correlates with that observed on liver
      biopsies in a single-center pediatric and young adult cohort. STUDY DESIGN: This
      cross-sectional study included patients undergoing liver biopsy as part of
      standard clinical care between January 25, 2012, and April 1, 2015, at Boston
      Children's Hospital. Eligible patients, with a variety of liver diseases, had CAP
      measurements within 1 year of biopsy. CAP values were compared across histologic
      steatosis grades using ANOVA. RESULTS: Sixty-nine patients (mean age, 16.0 +/-
      2.9 years; 62% male) were studied. CAP measurements were obtained at a median of
      1.3 months (IQR, 0.5-3.2) after biopsy. Of the 69 subjects, 23 had steatosis on
      biopsy. Mean CAP value (dB/m) for subjects with no steatosis was 198 +/- 37 vs
      290 +/- 47 for subjects with steatosis (P < .0001). There were statistically
      significant differences between CAP values in individuals with no steatosis vs
      mild/moderate steatosis (P < .0001), no steatosis vs marked steatosis (P <
      .0001), and mild/moderate vs marked steatosis (P = .004). CONCLUSION: This study
      demonstrated a difference in CAP between no steatosis and steatosis, and between
      grades of steatosis. CAP may be a useful noninvasive tool to detect hepatic
      steatosis in children.

PMID- 27039225
TI  - Transient Deformation of Neutrophils in Kawasaki Disease.
AB  - In the treatment of Kawasaki disease, resistance to high-dose immunoglobulin
      intravenous (IGIV) can occur. The neutrophil morphology analyses in 17 patients
      revealed that transient pseudo-Pelger-Huet anomaly was more frequently detected
      in the IGIV-resistant group. This finding may aid the prediction of IGIV
      resistance.

PMID- 27039226
TI  - Tinea Faciei in a 14-Day-Old Girl.

PMID- 27039227
TI  - Impact of Multiplex Polymerase Chain Reaction Testing for Respiratory Pathogens
      on Healthcare Resource Utilization for Pediatric Inpatients.
AB  - OBJECTIVE: To assess whether multiplex polymerase chain reaction (mPCR) vs non
      mPCR testing impacts the use of antibiotics, chest radiographs, and isolation
      precautions. STUDY DESIGN: We retrospectively compared use of antibiotics, chest
      radiographs, and isolation precautions for patients <18 years old (excluding
      neonates) hospitalized at a tertiary referral center tested for respiratory
      pathogens in the emergency department or during the first 2 hospital days, during
      2 periods: June 2010-June 2012 (non-mPCR group) vs October 2012-May 2014 (mPCR
      group). RESULTS: Subjects (n = 2430) in the mPCR group were older, had more
      complex chronic conditions, and were admitted to the pediatric intensive care
      unit more often compared with the non-mPCR (n = 2349) group. Subjects in the mPCR
      group had more positive tests (42.4% vs 14.4%, P < .01), received fewer days of
      antibiotics (4 vs 5 median antibiotic days, P < .01), fewer chest radiographs
      performed, (59% vs 78%, P < .01), and were placed in isolation longer (20 vs 0
      median isolation-hours, P < .01) compared with the non-mPCR group. In
      multivariable regression, patients tested with mPCR were less likely to receive
      antibiotics for >=2 days (OR 0.5, 95% CI 0.5-0.6), chest radiographs at admission
      (OR 0.4, 95% CI 0.3-0.4), and more likely to be in isolation for >=2 days (OR
      2.4, 95% CI 2.1-2.8) compared with the non-mPCR group. CONCLUSIONS: Use of mPCR
      testing for respiratory viruses among hospitalized patients was significantly
      associated with decreased healthcare resource utilization, including decreased
      use of antibiotics and chest radiographs, and increased use of isolation
      precautions.

PMID- 27039229
TI  - Hospitalizations at Nonfederal Facilities for Lower Respiratory Tract Infection
      in American Indian and Alaska Native Children Younger than 5 Years of Age, 1997
      2012.
AB  - OBJECTIVES: To evaluate hospitalizations at nonfederal facilities for lower
      respiratory tract infection (LRTI) in American Indian/Alaska Native (AI/AN)
      children and to compare associated rates and risk factors in AI/AN children and
      white children. STUDY DESIGN: We used Kids' Inpatient Database samples from 1997
      2012 to identify discharges in non-Hispanic AI/AN and white children ages <5
      years with a principal or secondary diagnosis code indicating LRTI. To address
      systematic underreporting and misclassification of race in administrative
      databases, population rates were estimated by deriving race- and year-specific
      denominators from hospital births. RESULTS: During the study period, LRTI
      associated discharge rates (per 1000) declined for white children (from 14.8 to
      10.9; P < .001 for trend). For AI/AN children, rates varied widely by census
      region and were highest in the West, where they ranged from 38.6 in 1997 to 26.7
      in 2012 (P = .35 for trend). Discharges in AI/AN children were associated with
      low household income, Medicaid insurance, and rural residence. In a case-cohort
      analysis of infants hospitalized with LRTI in 2012, discharge rates were higher
      for AI/AN infants than for white infants only in the West (72.8 vs 22.2; aOR,
      2.5; 95% CI, 1.8-3.4). CONCLUSIONS: Among young children who use nonfederal
      hospitals, LRTI-associated hospitalizations occur at substantially higher rates
      for AI/AN children than for white children. These hospitalizations occur at rates
      that are particularly high for AI/AN infants in the West, where rates are
      comparable with those reported for Indian Health Service enrollees.

PMID- 27039228
TI  - Corticosteroid Treatment and Growth Patterns in Ambulatory Males with Duchenne
      Muscular Dystrophy.
AB  - OBJECTIVES: To evaluate growth patterns of ambulatory males with Duchenne
      muscular dystrophy (DMD) treated with corticosteroids compared with ambulatory,
      steroid-naive males with DMD and age-matched unaffected general-population males
      and to test associations between growth and steroid treatment patterns among
      treated males. STUDY DESIGN: Using data from the Muscular Dystrophy Surveillance,
      Tracking, and Research Network, we identified a total of 1768 height, 2246
      weight, and 1755 body mass index (BMI) measurements between age 2 and 12 years
      for 324 ambulatory males who were treated with corticosteroids for at least 6
      months. Growth curve comparisons and linear mixed-effects modeling, adjusted for
      race/ethnicity and birth year, were used to evaluate growth and steroid treatment
      patterns (age at initiation, dosing interval, duration, cumulative dose).
      RESULTS: Growth curves for ambulatory males treated with corticosteroids showed
      significantly shorter stature, heavier weight, and greater BMI compared with
      ambulatory, steroid-naive males with DMD and general-population US males.
      Adjusted linear mixed-effects models for ambulatory males treated with
      corticosteroids showed that earlier initiation, daily dosing, longer duration,
      and greater dosages predicted shorter stature with prednisone. Longer duration
      and greater dosages predicted shorter stature for deflazacort. Daily prednisone
      dosing predicted lighter weight, but longer duration, and greater dosages
      predicted heavier weight. Early initiation, less than daily dosing, longer
      duration, and greater doses predicted greater BMIs. Deflazacort predicted shorter
      stature, but lighter weight, compared with prednisone. CONCLUSION: Prolonged
      steroid use is significantly associated with short stature and heavier weight.
      Growth alterations associated with steroid treatment should be considered when
      making treatment decisions for males with DMD.

PMID- 27039230
TI  - Reflex Myoclonic Epilepsy of Infancy: Seizures Induced by Tactile Stimulation.
AB  - Myoclonic epilepsy with reflex seizures in infancy is an extremely rare
      condition, in which seizures are provoked mainly by auditory or auditory-tactile
      stimuli. To increase the awareness of pediatricians regarding this
      underrecognized condition, we describe a child with seizures provoked only by the
      tactile stimulation of specific areas of the head and face. 

PMID- 27039231
TI  - Characterizing and Forecasting Individual Weight Changes in Term Neonates.
AB  - OBJECTIVES: To develop a mathematical, semimechanistic model characterizing
      physiological weight changes in term neonates, identify and quantify key maternal
      and neonatal factors influencing weight changes, and provide an online tool to
      forecast individual weight changes during the first week of life. STUDY DESIGN:
      Longitudinal weight data from 1335 healthy term neonates exclusively breastfed up
      to 1 week of life were available. A semimechanistic model was developed to
      characterize weight changes applying nonlinear mixed-effects modeling. Covariate
      testing was performed by applying a standard stepwise forward selection-backward
      deletion approach. The developed model was externally evaluated on 300 additional
      neonates collected in the same center. RESULTS: Weight changes during first week
      of life were described as a function of a changing net balance between time
      dependent rates of weight gain and weight loss. Males had higher birth weights
      (WT0) than females. Gestational age had a positive effect on WT0 and weight gain
      rate, whereas mother's age had a positive effect on WT0 and a negative effect on
      weight gain rate. The developed model showed good predictive performance when
      externally validated (bias = 0.011%, precision = 0.52%) and was able to
      accurately forecast individual weight changes up to 1 week with only 3 initial
      weight measurements (bias = -0.74%, precision = 1.54%). CONCLUSIONS: This
      semimechanistic model characterizes weight changes in healthy breastfed neonates
      during first week of life. We provide a user-friendly online tool allowing
      caregivers to forecast and monitor individual weight changes. We plan to validate
      this model with data from other centers and expand it with data from preterm
      neonates.

PMID- 27039232
TI  - Changes in Brown Adipose Tissue and Muscle Development during Infancy.
AB  - OBJECTIVE: To examine the relationship between brown adipose tissue (BAT) and
      muscle development, two tissues that derive from a common cell lineage, during
      the first 6 months of postnatal life. STUDY DESIGN: Thirty healthy term infants
      (15 males and females) underwent whole-body magnetic resonance imaging
      examinations. Measurements of BAT in the supraclavicular area as well as measures
      of trunk musculature and subcutaneous adiposity were obtained at birth and at 6
      months of age. RESULTS: Paraspinous musculature and subcutaneous white adipose
      tissue (WAT) increased, and the proportion of BAT in the supraclavicular area
      decreased during infancy. Although measures of BAT did not correlate with
      paraspinous musculature through the first 6 months of life (r = -0.35; P = .09),
      BAT was a significant predictor of paraspinous musculature after adjusting for
      weight, body length, and WAT (P = .002); infants with the smallest decreases in
      BAT had the greatest gains in musculature. In contrast, changes in BAT did not
      predict increases in subcutaneous WAT (P = .25) during infancy, which were
      primarily determined by body weight. CONCLUSIONS: Changes in BAT are associated
      with muscle development but not WAT accumulation in healthy infants. Studies are
      needed to determine the mechanism(s) by which BAT could facilitate muscle growth,
      and the degree to which decreased muscle mass, such as in preterm and low birth
      weight infants, is related to a deficiency of BAT.

PMID- 27039233
TI  - Allergy to several local anesthetics from the amide group.

PMID- 27039235
TI  - Intraoperative anaphylaxis to latex possibly facilitated by the administration of
      oxytocin and vasopressin.

PMID- 27039234
TI  - Antibiotics Are the Most Commonly Identified Cause of Perioperative
      Hypersensitivity Reactions.
AB  - BACKGROUND: Hypersensitivity reactions (HSRs) during the perioperative period are
      unpredictable and can be life threatening. Prospective studies for the evaluation
      of perioperative HSRs are lacking, and data on causative agents vary between
      different studies. OBJECTIVE: The objective of this study was to prospectively
      determine the success of a comprehensive allergy evaluation plan for patients
      with HSRs during anesthesia, including identification of a causative agent and
      outcomes during subsequent anesthesia exposure. METHODS: All patients referred
      for a perioperative HSR between November 2013 and March 2015, from a Boston
      teaching hospital, were evaluated using a standardized protocol with skin testing
      (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection
      of patient information, including characteristics of HSR during anesthesia. We
      reviewed the results of ST and/or test doses for all potential causative
      medications Event-related tryptase levels were reviewed when available. RESULTS:
      Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty
      two percent (13 of 25) were female with a median age of 52 (interquartile range
      43-66) years. The most frequently observed HSR systems were cutaneous (68%),
      cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive
      ST, was identified in 36% (9 of 25) of patients. The most common agent identified
      was cefazolin (6 of 9). After our comprehensive evaluation and management plan, 7
      (7 of 8, 88%) patients tolerated subsequent anesthesia. CONCLUSIONS: Cefazolin
      was the most commonly identified cause of a perioperative HSR in our study
      population. Skin testing patients within 6 months of a perioperative HSR may
      improve the odds of finding a positive result. Tolerance of subsequent anesthesia
      is generally achieved in patients undergoing our comprehensive evaluation.

PMID- 27039237
TI  - The "Tooth" About Wheezing.

PMID- 27039236
TI  - Assessment of Consistency of Fixed Airflow Obstruction Status during
      Budesonide/Formoterol Treatment and Its Effects on Treatment Outcomes in Patients
      with Asthma.
AB  - BACKGROUND: The consistency of fixed airflow limitation status during treatment
      in patients with asthma is unknown. OBJECTIVE: The objective of this study was to
      determine the consistency of fixed airflow obstruction (FAO) status during
      treatment and effects on treatment response. METHODS: This post hoc analysis from
      a 12-week study (NCT00652002) assessed patients aged 12 years or more with
      moderate-to-severe asthma randomized to twice-daily budesonide/formoterol
      (BUD/FM) via pressurized metered-dose inhaler (pMDI) 320/9 MUg, BUD pMDI 320 MUg,
      FM 9 MUg via dry-powder inhaler, or placebo. FAO status was assessed
      postbronchodilator at screening and after study drug administration at weeks 2,
      6, and 12 via the forced expiratory volume in 1 second to forced vital capacity
      (FEV1/FVC) ratio < lower limit of normal (LLN) (FAO+) or >= LLN (FAO-). Patients
      with persistent FAO- and FAO+ retained their screening FAO status at all visits.
      Patients with inconsistent FAO changed categories at least once during the study.
      Assessments included early withdrawal due to predefined worsening asthma events
      (PAEs), lung function, and symptoms. RESULTS: Of 386 patients, 29% had persistent
      FAO+, 31% inconsistent FAO, and 40% persistent FAO-. PAEs were lowest in the FAO-
      group overall and with BUD/FM treatment in patients with FAO+ and inconsistent
      FAO. Baseline demographics and treatment responses of the inconsistent FAO group
      were most similar to the FAO+ group. The greatest improvements in asthma control
      days and use of rescue medications were seen with BUD/FM treatment, regardless of
      FAO status. CONCLUSIONS: Approximately one third of patients with moderate-to
      severe asthma in this study had inconsistent FAO, and their treatment responses
      were most similar to patients with FAO+. Regardless of FAO status, patients
      treated with BUD/FM experienced the most improved treatment responses and fewest
      withdrawals due to PAEs.

PMID- 27039238
TI  - NOD2-associated autoinflammatory disease and immune deficiency.

PMID- 27039239
TI  - Intrasubject Variability in Total IgE Levels in Patients with Moderate to Severe
      Persistent Allergic Asthma Over 1 Year.
AB  - BACKGROUND: Longitudinal variability in serum IgE levels has not been
      prospectively studied in people with moderate to severe allergic asthma.
      OBJECTIVE: We investigated change in serum IgE concentrations over 1 year, and
      its relationship with lung function, asthma control, asthma pharmacotherapy,
      allergy season, asthma exacerbations, body mass index, and demographic factors.
      METHODS: Seventeen patients with moderate to severe persistent allergic asthma
      were followed for 1 year. Variability in serum IgE level was explored using a
      linear mixed regression model treating a change of 10% or more in IgE
      concentration and combined change of 10% or more and an absolute change of 50
      IU/mL as dichotomous variables. RESULTS: For consecutive visits every 2 months,
      the mean percent change in serum IgE level was 23 +/- 3 (P < .001). Probability
      of having a greater than 10% change in serum IgE level in a subsequent visit was
      69% (95% CI, 58%-78%; P < .001). Variability in IgE level could have affected
      clinical decisions for anti-IgE treatment (dosing and/or treatment candidacy) in
      7 of 17 patients. There were no statistically significant associations of IgE
      level variability with demographic characteristics and lung function,
      exacerbations, allergy season, Asthma Control Test scores, peak flow rates,
      pharmacotherapy, or body mass index. CONCLUSIONS: Serum IgE concentrations
      exhibit variability over time among individuals with moderate to severe
      persistent allergic asthma. The factors that contribute to IgE level variability
      and the impact of these findings on clinical outcomes deserve further study.

PMID- 27039240
TI  - [Geriatric Cardiology, fundamental for the cardiologist, vital for the
      geriatrician].

PMID- 27039243
TI  - Declaration for Integrative, Evidence-Based, End-of-Life Care that Incorporates
      Nonlocal Consciousness.

PMID- 27039241
TI  - Mind-body interactions in the regulation of airway inflammation in asthma: A PET
      study of acute and chronic stress.
AB  - BACKGROUND: Psychological stress has long been recognized as a contributing
      factor to asthma symptom expression and disease progression. Yet, the neural
      mechanisms that underlie this relationship have been largely unexplored in
      research addressing the pathophysiology and management of asthma. Studies that
      have examined the mechanisms of this relationship in the periphery suggest that
      it is the superimposition of acute stress on top of chronic stress that is of
      greatest concern for airway inflammation. METHODS: We compared asthmatic
      individuals with high and low levels of chronic life stress in their neural and
      peripheral physiological responses to the Trier Social Stress Test and a matched
      control task. We used FDG-PET to measure neural activity during performance of
      the two tasks. We used both circulating and airway-specific markers of asthma
      related inflammation to assess the impact of acute stress in these two groups.
      RESULTS: Asthmatics under chronic stress had a larger HPA-axis response to an
      acute stressor, which failed to show the suppressive effects on inflammatory
      markers observed in those with low chronic stress. Moreover, our PET data suggest
      that greater activity in the anterior insula during acute stress may reflect
      regulation of the effect of stress on inflammation. In contrast, greater activity
      in the mid-insula and perigenual anterior cingulate seems to reflect greater
      reactivity and was associated with greater airway inflammation, a more robust
      alpha amylase response, and a greater stress-induced increase in proinflammatory
      cytokine mRNA expression in airway cells. CONCLUSIONS: Acute stress is associated
      with increases in markers of airway inflammation in asthmatics under chronic
      stress. This relationship may be mediated by interactions between the insula and
      anterior cingulate cortex, that determine the salience of environmental cues, as
      well as descending regulatory influence of inflammatory pathways in the
      periphery.

PMID- 27039242
TI  - General intelligence is associated with subclinical inflammation in Nepalese
      children: A population-based plasma proteomics study.
AB  - Improving child cognition in impoverished countries is a public health priority.
      Yet, biological pathways and associated biomarkers of impaired cognition remain
      poorly understood and largely unknown, respectively. This study aimed to explore
      and quantify associations between functional plasma protein biomarkers and
      childhood intellectual test performance. We applied proteomics to quantify
      proteins in plasma samples of 249 rural Nepalese children, 6-8years of age who,
      1year later at 7-9years of age, were administered the Universal Nonverbal
      Intelligence Test (UNIT). Among 751 plasma proteins quantified, 22 were
      associated with UNIT scores, passing a false discovery rate threshold of 5.0%
      (q<0.05). UNIT scores were higher by 2.3-9.2 points for every 50% increase in
      relative abundance of two insulin-like growth factor binding proteins (IGFBPs),
      six subclasses of apolipoprotein (Apo) and transthyretin, and lower by 4.0-15.3
      points for each 50% increase in relative abundance of 13 proteins predominantly
      involved in inflammation. Among them, IGFBP-acid labile subunit, orosomucoid 1
      (ORM1), Apo C-I, and pyruvate kinase isoenzymes M1/M2 jointly explained 37% of
      the variance in UNIT scores. After additional adjustment for height-for-age Z
      score and household socio-economic status as indicators of long-term nutritional
      and social stress, associations with 6 proteins involved in inflammation,
      including ORM1, alpha-1-antichymotrypsin, reticulocalbin 1, and 3 components of
      the complement cascade, remained significant (q<0.05). Using untargeted
      proteomics, stable, constitutive facets of subclinical inflammation were
      associated with lower developmental test performance in this rural South Asian
      child population. Plasma proteomics may offer opportunities to identify
      functional, antecedent biomarkers of child cognitive development. 

PMID- 27039244
TI  - Sorption of copper onto low molecular weight chitosan derivative from aqueous
      solution.
AB  - In this study, sorption of copper onto low molecular weight chitosan derivative
      was studied. Experimental parameters such as pH of the solution (A), temperature
      (B), dose of the sorbent (C), and concentration of solution (D) were considered.
      The statistical results indicated that the dose of sorbent (C) and Cu (II)
      concentration (D) influenced removal efficiency at 5% significance level. Also,
      some interactions such as ABCD, ACD, ABC and AC affected the removal process. The
      sorbent was characterized with FTIR, SEM and TG/DSC. Freundlich isotherm model
      was the best isotherm model. The kinetic study results correlated well with the
      pseudo-second-order model. The thermodynamic studies revealed that the nature of
      copper sorption was spontaneous and endothermic. Strong affinity of the sorbent
      for copper (II) was revealed by the Isothermal Titration Calorimetry (ITC)
      technique.

PMID- 27039245
TI  - Reproductive effects in hybrid sparrow from a polluted area in Tunisia: Oxidative
      damage and altered testicular histomorphology.
AB  - Air pollution is a threat for human health and wildlife. The aim of this study is
      to assess the pathophysiological changes and the oxidative-antioxidative status
      in testicular tissues of 40 Hybrid sparrows collected from four areas in Gabes
      city, one of the most polluted areas in Tunisia. The testis histopathological
      analysis revealed alterations in birds from Ghannouche, the polluted area. The
      thiobarbituric acid reactive substance (TBARS) levels were higher in testis of
      birds from the contaminated site compared to less polluted areas indicating
      oxidative damage to membrane lipids. Antioxidant enzyme activities (superoxide
      dismutase and catalase) were lower in testis sparrows from the polluted site
      compared with the reference site, suggesting deficiency of the antioxidant system
      to compensate for oxidative stress. Overall, our results suggest that the hybrid
      sparrow offers a suitable model for biomonitoring programs of atmosphere
      pollutants and the selected biomarkers could be useful tool to evaluate pollution
      impacts in living organisms.

PMID- 27039246
TI  - Effect of natural and synthetic surfactants on crude oil biodegradation by
      indigenous strains.
AB  - Hydrocarbon pollution is a worldwide problem. In this study, five surfactants
      containing SDS, LAS, Brij 30, Tween 80 and biosurfactant were used to evaluate
      their effect on crude oil biodegradation. Hydrocarbon degrading bacteria were
      isolated from oil production water. The biosurfactant used was a kind of cyclic
      lipopeptide produced by Bacillus subtilis strain WU-3. Solubilization test showed
      all the surfactants could apparently increase the water solubility of crude oil.
      The microbial adhesion to the hydrocarbon (MATH) test showed surfactants could
      change cell surface hydrophobicity (CSH) of microbiota, depending on their
      species and concentrations. Microcalorimetric experiments revealed these
      surfactants exhibited toxicity to microorganisms at high concentrations (above 1
      CMC), except for SDS which showed low antibacterial activity. Surfactant
      supplementation (about 0.1 and 0.2 CMC) could improve degradation rate of crude
      oil slightly, while high surfactant concentration (above 1 CMC) may decrease the
      degradation rate from 50.5% to 28.9%. Those findings of this work could provide
      guidance for the application of surfactants in bioremediation of oil pollution.

PMID- 27039247
TI  - Placenta previa with early opening of the uterine isthmus is associated with high
      risk of bleeding during pregnancy, and massive haemorrhage during caesarean
      delivery.
AB  - OBJECTIVE: To demonstrate the relationship between the timing of opening of the
      uterine isthmus and bleeding during pregnancy and caesarean section in patients
      with placenta previa. METHODS: A prospective observational study was conducted at
      a single perinatal centre. All patients with placenta previa, diagnosed between
      20 and 22 weeks of gestation, who were followed up at the study hospital and
      underwent caesarean section were enrolled. The condition of the uterine isthmus
      was examined every 2 weeks. The timing (in gestational weeks) of complete opening
      of the uterine isthmus was determined. Patients were divided into two groups:
      patients in whom the uterine isthmus opened before 25 weeks of gestation (EO
      previa), and patients in whom the uterine isthmus opened after 25 weeks of
      gestation (LO-previa). The frequency of bleeding during pregnancy and the amount
      of intra-operative bleeding were compared between the two groups. RESULTS: Forty
      four cases of EO-previa and 55 cases of LO-previa were analysed. Complete
      placenta previa at delivery was observed more frequently in the EO-previa group
      than in the LO-previa group (88.6% vs 47.3%, p<0.001). An emergency caesarean
      section due to active bleeding was performed more frequently in the EO-previa
      group (48%) than in the LO-previa group (25%) (p=0.021). The frequency of massive
      haemorrage (>2500ml) during caesarean section was higher in the EO-previa group
      than in the LO-previa group (25% vs 9%, p=0.033). CONCLUSION: Placenta previa was
      associated with a high risk of bleeding leading to emergency caesarean section
      during pregnancy, and massive haemorrhage during caesarean section in patients in
      whom the uterine isthmus opened before 25 weeks of gestation.

PMID- 27039248
TI  - Characteristics and attitudes of women in relation to chosen fertility
      preservation techniques: a prospective, multicenter questionnaire-based study
      with 144 participants.
AB  - OBJECTIVE: What are the patients attitudes about their fertility and about the
      counselling process at the time when fertility preservation counselling is
      performed? STUDY DESIGN: A survey regarding fertility concerns and counselling
      performance in relation to the chosen fertility preservation procedure such as no
      treatment, GnRH agonists, and freezing of ovarian tissue or oocytes/zygotes was
      prospectively conducted in four university centres and one private centre, all
      belonging to the network FertiPROTEKT in Germany and Switzerland. RESULTS: All
      women (n=145) received a questionnaire at the first counselling appointment. The
      mean age of the patients was 30 years (+/-5.8, range 17-43 years). 91% were
      referred by their treating oncologists. Single patients preferred invasive
      strategies, such as freezing of oocytes/zygotes (44.3%) or freezing of ovarian
      tissue (36%), whereas only 19.7% opted for no treatment/GnRH agonists. In married
      couples, the proportions were 28.9%, 31.1% and 40.0% respectively. Women without
      children also opted more frequently for invasive strategies, such as freezing of
      oocytes/zygotes (84.5%) or freezing of ovarian tissue (74.1%), and less
      frequently for no treatment/GnRH agonists (63.3%). Physical and psychological
      status, current and future fertility concerns and satisfaction with the
      counselling process were equal in all treatment groups. CONCLUSION: As fertility
      concerns and attitudes about the counselling process were independent from the
      fertility preservation procedure chosen, the preferred treatment can hardly be
      predicted and therefore all women should be counselled about all possible
      fertility preservation techniques.

PMID- 27039249
TI  - Pregnancy loss: French clinical practice guidelines.
AB  - In intrauterine pregnancies of uncertain viability with a gestational sac without
      a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements
      <25mm), the suspected pregnancy loss should only be confirmed after a follow-up
      scan at least 14 days later shows no embryo with cardiac activity (Grade C). In
      intrauterine pregnancies of uncertain viability with an embryo <7mm on
      transvaginal ultrasound, the suspected pregnancy loss should only be confirmed
      after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown
      location after transvaginal ultrasound (i.e. not visible in the uterus), a
      threshold of at least 3510IU/l for the serum human chorionic gonadotrophin assay
      is recommended; above that level, a viable intrauterine pregnancy can be ruled
      out (Grade C). Postponing conception after an early miscarriage in women who want
      a new pregnancy is not recommended (Grade A). A work-up for women with recurrent
      pregnancy loss should include the following: diabetes (Grade A), antiphospholipid
      syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and
      anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12)
      (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B),
      diminished ovarian reserve (Grade C), and a uterine malformation or an acquired
      uterine abnormality amenable to surgical treatment (Grade C). The treatment
      options recommended for women with a missed early miscarriage are vacuum
      aspiration (Grade A) or misoprostol (Grade B); and the treatment options
      recommended for women with an incomplete early miscarriage are vacuum aspiration
      (Grade A) or expectant management (Grade A). In the absence of both
      chorioamnionitis and rupture of the membranes, women with a threatened late
      miscarriage and an open cervix, with or without protrusion of the amniotic sac
      into the vagina, should receive McDonald cerclage, tocolysis with indomethacin,
      and antibiotics (Grade C). Among women with a threatened late miscarriage and an
      isolated undilated shortened cervix (<25mm on ultrasound), cerclage is only
      indicated for those with a history of either late miscarriage or preterm delivery
      (Grade A). Among women with a threatened late miscarriage, an isolated undilated
      shortened cervix (<25mm on ultrasound) and no uterine contractions, daily
      treatment with vaginal progesterone up to 34 weeks of gestation is recommended
      (Grade A). Hysteroscopic section of the septum is recommended for women with a
      uterine septum and a history of late miscarriage (Grade C). Correction of
      acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is
      recommended after three early or late miscarriages (Grade C). Prophylactic
      cerclage is recommended for women with a history of three late miscarriages or
      preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin
      at a preventive dose are recommended for women with obstetric antiphospholipid
      syndrome (Grade A). Glycaemic levels should be controlled before conception in
      women with diabetes (Grade A). 

PMID- 27039250
TI  - Synthesis of 4-substituted nipecotic acid derivatives and their evaluation as
      potential GABA uptake inhibitors.
AB  - In this study, we disclose the design and synthesis of novel 4-susbtituted
      nipecotic acid derivatives as inhibitors of the GABA transporter mGAT1. Based on
      molecular modeling studies the compounds are assumed to adopt a binding pose
      similar to that of the potent mGAT1 inhibitor nipecotic acid. As substitution in
      4-position should not cause an energetically unfavorable orientation of nipecotic
      acid as it is the case for N-substituted derivatives this is expected to lead to
      highly potent binders. For the synthesis of novel 4-substituted nipecotic acid
      derivatives a linear synthetic strategy was employed. As a key step, palladium
      catalyzed cross coupling reactions were used to attach the required biaryl
      moieties to the omega-position of the alkenyl- or alkynyl spacers of varying
      length in the 4-position of the nipecotic acid scaffold. The resulting amino
      acids were characterized with respect to their binding affinities and inhibitory
      potencies at mGAT1. Though the biological activities found were generally
      insignificant to poor, two compounds, one of which possesses a reasonable binding
      affinity for mGAT1, rac-57, the other a notable inhibitory potency at mGAT4, rac
      84, both displaying a slight subtype selectivity for the individual transporters,
      could be identified. 

PMID- 27039251
TI  - Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as
      selective gelatinase inhibitors.
AB  - As our ongoing work on research of gelatinase inhibitors, an array of hydrazide
      containing peptidomimetic derivatives bearing quinoxalinone as well as spiro
      heterocyclic backbones were designed, synthesized, and assayed for their in vitro
      enzymatic inhibitory effects. The results demonstrated that both the
      quinoxalinone (series I and II) and 1,4-dithia-7-azaspiro[4,4]nonane-based
      hydrazide peptidomimetics (series III) displayed remarkably selectivity towards
      gelatinase A as compared to APN, with IC50 values in the micromole range.
      Structure-activity relationships were herein briefly discussed. Given evidences
      have validated that gelatinase inhibition may be contributable to the therapy of
      HIV-1 infection, all the target compounds were also submitted to the preliminary
      in vitro anti-HIV-1 evaluation. It resulted that gelatinase inhibition really has
      positive correlation with anti-HIV-1 activity, especially compounds 4m and 7h,
      which gave enhanced gelatinase inhibition in comparison with the positive control
      LY52, and also decent anti-HIV-1 potencies. The FlexX docking results provided a
      straightforward insight into the binding pattern between inhibitors and
      gelatinase, as well as the selective inhibition towards gelatinase over APN.
      Collectively, our research encouraged potent gelatinase inhibitors might be used
      in the development of anti-HIV-1 agents. And else, compounds 4m and 7h might be
      promising candidates to be considered for further chemical optimization. 

PMID- 27039252
TI  - Makings of a brittle bone: Unexpected lessons from a low protein diet study of a
      mouse OI model.
AB  - Glycine substitutions in type I collagen appear to cause osteogenesis imperfecta
      (OI) by disrupting folding of the triple helix, the structure of which requires
      Gly in every third position. It is less clear, however, whether the resulting
      bone malformations and fragility are caused by effects of intracellular
      accumulation of misfolded collagen on differentiation and function of
      osteoblasts, effects of secreted misfolded collagen on the function of bone
      matrix, or both. Here we describe a study originally conceived for testing how
      reducing intracellular accumulation of misfolded collagen would affect mice with
      a Gly610 to Cys substitution in the triple helical region of the alpha2(I) chain.
      To stimulate degradation of misfolded collagen by autophagy, we utilized a low
      protein diet. The diet had beneficial effects on osteoblast differentiation and
      bone matrix mineralization, but also affected bone modeling and suppressed
      overall animal growth. Our more important observations, however, were not related
      to the diet. They revealed how altered osteoblast function and deficient bone
      formation by each cell caused by the G610C mutation combined with increased
      osteoblastogenesis might make the bone more brittle, all of which are common OI
      features. In G610C mice, increased bone formation surface compensated for reduced
      mineral apposition rate, resulting in normal cortical area and thickness at the
      cost of altering cortical modeling process, retaining woven bone, and reducing
      the ability of bone to absorb energy through plastic deformation. Reduced
      collagen and increased mineral density in extracellular matrix of lamellar bone
      compounded the problem, further reducing bone toughness. The latter observations
      might have particularly important implications for understanding OI
      pathophysiology and designing more effective therapeutic interventions.

PMID- 27039253
TI  - No Need to Sugarcoat the Message: Is Cardiovascular Risk Reduction From SGLT2
      Inhibition Related to Natriuresis?

PMID- 27039254
TI  - Long-term Follow-up of a Reused Kidney Allograft.

PMID- 27039255
TI  - Severe rhabdomyolysis from red-bellied black snake (Pseudechis porphyriacus)
      envenoming despite antivenom.
AB  - Envenoming by the Australian red-bellied black snake (Pseudechis porphyriacus)
      causes non-specific systemic symptoms, anticoagulant coagulopathy, myotoxicity
      and local effects. Current management for systemic envenoming includes
      administration of one vial of tiger snake antivenom within 6 h of the bite to
      prevent myotoxicity. We present a case of severe rhabdomyolysis in a 16 year old
      male which developed despite early administration of one vial of tiger snake
      antivenom. Free venom was detected after the administration of antivenom
      concurrent with rapidly decreasing antivenom concentrations. The case suggests
      that insufficient antivenom was administered and the use of larger doses of
      antivenom need to be explored for red-bellied black snake envenoming. 

PMID- 27039256
TI  - Response to Letter: Psychometric properties of the Tinnitus Functional Index
      (TFI): Assessment in a UK research volunteer population.

PMID- 27039257
TI  - Social housing of non-rodents during cardiovascular recordings in safety
      pharmacology and toxicology studies.
AB  - INTRODUCTION: The Safety Pharmacology Society (SPS) and National Centre for the
      Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a
      survey and workshop in 2015 to define current industry practices relating to
      housing of non-rodents during telemetry recordings in safety pharmacology and
      toxicology studies. The aim was to share experiences, canvas opinion on the study
      procedures/designs that could be used and explore the barriers to social housing.
      METHODS: Thirty-nine sites, either running studies (Sponsors or Contract Research
      Organisations, CROs) and/or outsourcing work responded to the survey (51% from
      Europe; 41% from USA). RESULTS: During safety pharmacology studies, 84, 67 and
      100% of respondents socially house dogs, minipigs and non-human primates (NHPs)
      respectively on non-recording days. However, on recording days 20, 20 and 33% of
      respondents socially house the animals, respectively. The main barriers for
      social housing were limitations in the recording equipment used, study design and
      animal temperament/activity. During toxicology studies, 94, 100 and 100% of
      respondents socially house dogs, minipigs and NHPs respectively on non-recording
      days. However, on recording days 31, 25 and 50% of respondents socially house the
      animals, respectively. The main barriers for social housing were risk of damage
      to and limitations in the recording equipment used, food consumption recording
      and temperament/activity of the animals. CONCLUSIONS: Although the majority of
      the industry does not yet socially house animals during telemetry recordings in
      safety pharmacology and toxicology studies, there is support to implement this
      refinement. Continued discussions, sharing of best practice and data from
      companies already socially housing, combined with technology improvements and
      investments in infrastructure are required to maintain the forward momentum of
      this refinement across the industry.

PMID- 27039258
TI  - Rat cardiovascular telemetry: Marginal distribution applied to positive control
      drugs.
AB  - Cardiovascular effects are considered frequent during drug safety testing. This
      investigation aimed to characterize the pharmacological response of the conscious
      telemetered rat in vivo model to known cardiovascular active agents. These
      effects were analyzed using statistical analysis and cloud representation with
      marginal distribution curves for the contractility index and heart rate as to
      assess the effect relationship between cardiac variables. Arterial blood
      pressure, left ventricular pressure, electrocardiogram and body temperature were
      monitored. The application of data cloud with marginal distribution curves to
      heart rate and contractility index provided an interesting tactic during the
      interpretation of drug-induced changes particularly during selective time
      resolution (i.e. marginal distribution curves restricted to Tmax). Taken
      together, the present data suggests that marginal distribution curves can be a
      valuable interpretation strategy when using the rat cardiovascular telemetry
      model to detect drug-induced cardiovascular effects. Marginal distribution curves
      could also be considered during the interpretation of other inter-dependent
      parameters in safety pharmacology studies. 

PMID- 27039260
TI  - Consensus document and recommendations on the use of natriuretic peptides in
      clinical practice.
AB  - Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis
      and treatment of patients with heart failure. Natriuretic peptides are used in
      various healthcare settings (consultations, emergency department,
      hospitalization, laboratory) and by various primary care and specialised
      professionals. However, their use in clinical practice is still scare and uneven.
      Properly using and interpreting natriuretic peptides in clinical practice
      requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and
      postlaboratory (interpretation and integration of clinical data) expertise. The
      objective of this consensus document, developed by several scientific societies,
      is to update the necessary concepts and expertise on natriuretic peptides that
      enable its application in the diagnosis, prognosis and treatment of heart
      failure, in various healthcare environments. 

PMID- 27039261
TI  - A Highly Sensitive and Drug-Tolerant Anti-Drug Antibody Screening Assay for
      Ixekizumab using Affinity Capture Elution.

PMID- 27039259
TI  - TGF-beta signaling in liver and gastrointestinal cancers.
AB  - Transforming Growth Factor-beta (TGF-beta) plays crucial and complex roles in
      liver and gastrointestinal cancers. These include a multitude of distinct
      functions, such as maintaining stem cell homeostasis, promoting fibrosis, immune
      modulating, as a tumor suppressor and paradoxically, as a tumor progressor.
      However, key mechanisms for the switches responsible for these distinct actions
      are poorly understood, and remain a challenge. The Cancer Genome Atlas (TCGA)
      analyses and genetically engineered mouse models now provide an integrated
      approach to dissect these multifaceted and context-dependent driving roles of the
      TGF-beta pathway. In this review, we will discuss the molecular mechanisms of TGF
      beta signaling, focusing on colorectal, gastric, pancreatic, and liver cancers.
      Novel drugs targeting the TGF-beta pathway have been developed over the last
      decade, and some have been proven effective in clinical trials. A better
      understanding of the TGF-beta pathway may improve our ability to target it, thus
      providing more tools to the armamentarium against these deadly cancers.

PMID- 27039262
TI  - Identification of Gene Mutations and Fusion Genes in Patients with Sezary
      Syndrome.
AB  - Sezary syndrome is a leukemic form of cutaneous T-cell lymphoma with an
      aggressive clinical course. The genetic etiology of the disease is poorly
      understood, with chromosomal abnormalities and mutations in some genes being
      involved in the disease. The goal of our study was to understand the genetic
      basis of the disease by looking for driver gene mutations and fusion genes in 15
      erythrodermic patients with circulating Sezary cells, 14 of them fulfilling the
      diagnostic criteria of Sezary syndrome. We have discovered genes that could be
      involved in the pathogenesis of Sezary syndrome. Some of the genes that are
      affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and
      RAG2, with some of them mutated in more than one patient. We observed several
      somatic copy number variations shared between patients, including deletions and
      duplications of large segments of chromosome 17. Genes with potential function in
      the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sezary
      syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1.
      Furthermore, we discovered several fusion events of interest involving RASA2,
      NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the
      development of potential therapeutic approaches for this aggressive disease.

PMID- 27039263
TI  - Morbidity and Mortality of Stevens-Johnson Syndrome and Toxic Epidermal
      Necrolysis in United States Adults.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life
      threatening disorders. Our study objective was to describe the incidence, costs
      of care, length of stay, comorbidities, and mortality of SJS and TEN in US
      adults. The Nationwide Inpatient Sample 2009-2012, containing a 20% sample of all
      US hospitalizations, was analyzed. We used a validated approach involving
      International Classification of Disease, 9th edition, Clinical Modification codes
      to identify SJS, SJS/TEN, and TEN (n = 2,591, n = 502, and n = 564,
      respectively). The mean estimated incidences of SJS, SJS/TEN, and TEN were 9.2,
      1.6, and 1.9 per million adults per year, respectively. SJS/TEN was associated
      with nonwhite race, particularly Asians (odds ratio = 3.27, 95% confidence
      interval = 3.02-3.54) and blacks (odds ratio = 2.01, 95% confidence interval =
      1.92-2.10). Significantly prolonged length of stay and higher costs of care (SJS:
      9.8 +/- 0.3 days, $21,437 +/- $807; SJS/TEN: 16.5 +/- 1.0 days, $58,954 +/-
      $5,238; TEN: 16.2 +/- 1.0 days, $53,695 +/- $4,037) were observed compared with
      all other admissions (4.7 +/- 0.02 days, $11,281 +/- $98). Mean adjusted
      mortality was 4.8% for SJS, 19.4% for SJS/TEN, and 14.8% for TEN. SJS, SJS/TEN,
      and TEN pose a substantial health care burden. Predictors of mortality included
      increasing age, increasing number of chronic conditions, infection (septicemia,
      pneumonia, tuberculosis), hematological malignancy (non-Hodgkin's lymphoma,
      leukemia), and renal failure (P <= 0.03 for all). Further studies are needed to
      confirm mortality findings to improve prognostication of SJS/TEN.

PMID- 27039264
TI  - Segmental pairs of giant insect cells discharge presumptive immune proteins at
      each larval molt.
AB  - A pair of massive secretory cells exists within each thoracic and the nine
      abdominal segments of Manduca larvae. Each of these cells is nestled between the
      dorsal integument and underlying muscles. Contents of large vacuoles in these
      cells are abruptly discharged at each molt and have always been considered to
      contribute to shedding and/or formation of cuticle. Peanut agglutinin is a
      specific lectin label for these secretory vacuoles; vacuoles label intensely
      immediately before each molt as vacuoles attain their maximal size. Contents of
      vacuoles are restored after each molt and throughout most of each intermolt.
      During the molt cycle these cells secrete contents of their vacuoles into the
      interior hemocoel rather than onto the exterior cuticle. Vacuoles discharge via a
      distinctive mechanism involving partitioning of contents into numerous vesicles
      that move to the cell surface. Dermal secretory cells were dissected from larvae
      before and after the 4th-5th instar molt. Proteins from pre-molt and post-molt
      secretory cells were separated by two-dimensional electrophoresis to establish
      which proteins are discharged at the molt. While secreted proteins are novel, all
      have presumptive roles in immune responses. Dermal secretory cells may represent
      a new, unsuspected component of the innate immune system that release their
      proteins during the vulnerable molting period of an insect's life.

PMID- 27039265
TI  - Xenopus genomic data and browser resources.
AB  - The two species of Xenopus most commonly used in biomedical research are the
      diploid Xenopus (Silurana) tropicalis and the tetraploid Xenopus laevis. The X.
      tropicalis genome sequence has been available since 2010 and this year the X.
      laevis, genome from two distinct genetic backgrounds has been published. Multiple
      genome assemblies available for both species and transcriptomic and epigenetic
      data sets are growing rapidly, all of which are available from a variety of web
      resources. This review describes the contents of these resources, how to locate
      and download genomic data, and also how to view and manipulate these data on
      various public genome browsers, with an emphasis on Xenbase, the Xenopus model
      organism database.

PMID- 27039266
TI  - Characteristics of childhood lead poisoning among Tennessee children ages one to
      five years, 2009-2013.

PMID- 27039267
TI  - The extent and nature of food advertising to children on Spanish television in
      2012 using an international food-based coding system and the UK nutrient
      profiling model.
AB  - OBJECTIVE: To examine the extent and nature of food television advertising
      directed at children in Spain using an international food-based system and the
      United Kingdom nutrient profile model (UKNPM). STUDY DESIGN: Cross-sectional
      study of advertisements of food and drinks shown on five television channels over
      7 days in 2012 (8am-midnight). METHODS: Showing time and duration of each
      advertisement was recorded. Advertisements were classified as core (nutrient
      rich/calorie-low products), non-core, or miscellaneous based on the international
      system, and either healthy/less healthy, i.e., high in saturated fats, trans
      fatty acids, salt, or free sugars (HFSS), according to UKNPM. RESULTS: The food
      industry accounted for 23.7% of the advertisements (4212 out of 17,722) with 7.5
      advertisements per hour of broadcasting. The international food-based coding
      system classified 60.2% of adverts as non-core, and UKNPM classified 64.0% as
      HFSS. Up to 31.5% of core, 86.8% of non-core, and 8.3% of miscellaneous
      advertisements were for HFSS products. The percentage of advertisements for HFSS
      products was higher during reinforced protected viewing times (69.0%), on
      weekends (71.1%), on channels of particular appeal to children and teenagers
      (67.8%), and on broadcasts regulated by the Spanish Code of self-regulation of
      the advertising of food products directed at children (70.7%). CONCLUSIONS: Both
      schemes identified that a majority of foods advertised were unhealthy, although
      some classification differences between the two systems are important to
      consider. The food advertising Code is not limiting Spanish children's exposure
      to advertisements for HFSS products, which were more frequent on Code-regulated
      broadcasts and during reinforced protected viewing time.

PMID- 27039268
TI  - Persistent virus and addiction modules: an engine of symbiosis.
AB  - The giant DNA viruses are highly prevalent and have a particular affinity for the
      lytic infection of unicellular eukaryotic host. The giant viruses can also be
      infected by inhibitory virophage which can provide lysis protection to their
      host. The combined protective and destructive action of such viruses can define a
      general model (PD) of virus-mediated host survival. Here, I present a general
      model for role such viruses play in the evolution of host symbiosis. By
      considering how virus mixtures can participate in addiction modules, I provide a
      functional explanation for persistence of virus derived genetic 'junk' in their
      host genomic habitats.

PMID- 27039269
TI  - Updating strategies for isolating and discovering giant viruses.
AB  - Almost fifteen years ago, the discovery of Acanthamoeba polyphaga mimivirus, the
      first giant virus, changed how we define a virus. It was discovered incidentally
      in a process of isolating Legionella sp. from environmental samples in the
      context of pneumonia epidemics using a co-culture system with Acanthamoeba. Since
      then, much effort and improvement has been put into the original technique. In
      addition to the known families of Mimiviridae and Marseilleviridae, four new
      proposed families of giant viruses have been isolated: Pandoravirus, Pithovirus,
      Faustovirus and Mollivirus. Major improvements were based on enrichment systems,
      targeted use of antibiotics and high-throughput methods. The most recent
      development, using flow cytometry for isolation and presumptive identification
      systems, opens a path to large environmental surveys that may discover new giant
      virus families in new protozoa supports used for culture support.

PMID- 27039270
TI  - Giants among larges: how gigantism impacts giant virus entry into amoebae.
AB  - The proposed order Megavirales comprises the nucleocytoplasmic large DNA viruses
      (NCLDV), infecting a wide range of hosts. Over time, they co-evolved with
      different host cells, developing various strategies to penetrate them.
      Mimiviruses and other giant viruses enter cells through phagocytosis, while
      Marseillevirus and other large viruses explore endocytosis and macropinocytosis.
      These differing strategies might reflect the evolution of those viruses. Various
      scenarios have been proposed for the origin and evolution of these viruses,
      presenting one of the most enigmatic issues to surround these microorganisms. In
      this context, we believe that giant viruses evolved independently by massive
      gene/size gain, exploring the phagocytic pathway of entry into amoebas. In
      response to gigantism, hosts developed mechanisms to evade these parasites.

PMID- 27039271
TI  - Endemic plants harbour specific Trichoderma communities with an exceptional
      potential for biocontrol of phytopathogens.
AB  - Trichoderma strains exhibit enormous potential for applications in biotechnology,
      in particular as biocontrol agents against pathogens. However, little is known
      about the diversity of plant-associated Trichoderma communities at a global scale
      and their antagonistic spectrum. In order to gather information about structure
      and function, we compared Trichoderma biomes of endemic (Aeonium, Diospyros,
      Hebe, Rhododendron) and cosmopolitan plants (Zea mays) in a global study
      encompassing the area Northwest Africa to New Zealand via the European Alps and
      Madagascar. At the quantitative level we found no differences between
      cosmopolitan and endemic plants. Statistically significant differences were
      detected at the qualitative level: Trichoderma populations of endemic plants were
      highly specific and diverse with hot spots appearing in Madagascar and New
      Zealand. By contrast, maize plants from all sites shared the majority of
      Trichoderma species (65.5%). Interestingly, the high above ground biodiversity in
      ecosystems containing endemic plants was confirmed by a high below ground
      Trichoderma diversity. Despite the differences, we found a global Trichoderma
      core community shared by all analysed plants, which was dominated by T. koningii
      and T. koningiopsis. Amplicon-based network analyses revealed a high similarity
      between maize Trichoderma grown world-wide and distinct populations of endemic
      plants. Furthermore, Trichoderma strains from endemic plants showed a higher
      antagonistic activity against fungal pathogens compared to maize-associated
      strains. Our results showed that endemic plants are associated with a specific
      Trichoderma microbiome which possesses a high antagonistic activity indicating
      that it has potential to be used for biocontrol purposes. 

PMID- 27039272
TI  - Development of a standard documentation protocol for communicating exposure
      models.
AB  - An important step in building a computational model is its documentation; a
      comprehensive and structured documentation can improve the model applicability
      and transparency in science/research and for regulatory purposes. This is
      particularly crucial and challenging for environmental and/or human exposure
      models that aim to establish quantitative relationships between personal exposure
      levels and their determinants. Exposure models simulate the transport and fate of
      a contaminant from the source to the receptor and may involve a large set of
      entities (e.g. all the media the contaminants may pass though). Such complex
      models are difficult to be described in a comprehensive, unambiguous and
      accessible way. Bad communication of assumptions, theory, structure and/or
      parameterization can lead to lack of confidence by the user and it may be source
      of errors. The goal of this paper is to propose a standard documentation protocol
      (SDP) for exposure models, i.e. a generic format and a standard structure by
      which all exposure models could be documented. For this purpose, a CEN (European
      Committee for Standardisation) workshop was set up with objective to agree on
      minimum requirements for the amount and type of information to be provided on
      exposure models documentation along with guidelines for the structure and
      presentation of the information. The resulting CEN workshop agreement (CWA) was
      expected to facilitate a more rigorous formulation of exposure models description
      and the understanding by users. This paper intends to describe the process
      followed for defining the SDP, the standardisation approach, as well as the main
      components of the SDP resulting from a wide consultation of interested
      stakeholders. The main outcome is a CEN CWA which establishes terms and
      definitions for exposure models and their elements, specifies minimum
      requirements for the amount and type of information to be documented, and
      proposes a structure for communicating the documentation to different users. 

PMID- 27039273
TI  - Decay rates of faecal indicator bacteria from sewage and ovine faeces in brackish
      and freshwater microcosms with contrasting suspended particulate matter
      concentrations.
AB  - To safeguard human health, legislative measures require the monitoring of faecal
      indicator bacteria (FIB) concentrations in recreational and shellfish waters.
      Consequently, numerous studies have focussed on FIB survival in the water column
      and more recently in estuarine sediments. However, there is a paucity of
      information regarding the influence of contrasting suspended particulate matter
      (SPM) concentrations on the survival of FIB in the water column of estuaries.
      Here, microcosms containing freshwater or brackish water with low, high and
      extreme SPM concentrations were inoculated with sewage and ovine faeces and the
      decay rate of Escherichia coli, coliforms and enterococci were determined by
      enumeration over five consecutive days. E. coli derived from ovine faeces
      proliferated and persisted at high levels in both freshwater and brackish
      microcosms (no decay), whereas ovine enterococci demonstrated a net decay over
      the duration of the experiment. Furthermore, SPM concentration had a significant
      effect on the decay rates of both E. coli and enterococci from ovine faeces in
      brackish microcosms, but decay rate was greater at low SPM concentrations for E.
      coli, whereas the opposite was observed for enterococci, whose decay rates
      increased as SPM concentration increased. E. coli, enterococci and coliforms
      derived from wastewater demonstrated a net decay in both freshwater and brackish
      microcosms, with contrasting effects of SPM concentration on decay rate. In
      addition, some FIB groups demonstrated contrasting responses (decay or
      proliferation) in the first 24h following inoculation into freshwater versus
      brackish microcosms. Overall, SPM concentrations influenced the proliferation and
      decay rates of FIB in brackish waters, but had minimal influence in freshwater.
      These results demonstrate that the survival rates of FIB in aquatic environments
      are system specific, species and source dependent, and influenced by SPM
      concentration. This study has important implications for catchment-based risk
      assessments and source apportionment of FIB pollution in aquatic environments.

PMID- 27039274
TI  - Activated carbon from pyrolysed sugarcane bagasse: Silver nanoparticle
      modification and ecotoxicity assessment.
AB  - Activated carbon from pyrolysed sugarcane bagasse (ACPB) presented pore size
      ranges from 1.0 to 3.5nm, and surface area between 1200 and 1400m(2)g(-1) that is
      higher than commonly observed to commercial activated carbon. The ACPB material
      was successfully loaded with of silver nanoparticles with diameter around 35nm
      (0.81wt.%). X-ray photoelectron spectroscopy (XPS) analyses showed that the
      material surface contains metallic/Ag(0) (93.60wt.%) and ionic/Ag(+) states
      (6.40wt.%). The adsorption capacity of organic model molecules (i.e. methylene
      blue and phenol) was very efficient to ACPB and ACPB loaded with silver
      nanoparticles (ACPB-AgNP), indicating that the material modification with silver
      nanoparticles has not altered its adsorption capacity. ACPB-AgNP inhibited
      bacteria growth (Escherichia coli), it is a promising advantage for the use of
      these materials in wastewater treatment and water purification processes.
      However, ACPB-AgNP showed environmental risks, with toxic effect to the aquatic
      organism Hydra attenuata (i.e. LC50 value of 1.94mgL(-1)), and it suppressed root
      development of Lycopersicum esculentum plant (tomato). Finally, this work draw
      attention for the environmental implications of activated carbon materials
      modified with silver nanoparticles. 

PMID- 27039275
TI  - Reservoirs and water management influence fish mercury concentrations in the
      western United States and Canada.
AB  - Anthropogenic manipulation of aquatic habitats can profoundly alter mercury (Hg)
      cycling and bioaccumulation. The impoundment of fluvial systems is among the most
      common habitat manipulations and is known to increase fish Hg concentrations
      immediately following impoundment. However, it is not well understood how Hg
      concentrations differ between reservoirs and lakes at large spatial and temporal
      scales or how reservoir management influences fish Hg concentrations. This study
      evaluated total Hg (THg) concentrations in 64,386 fish from 883 reservoirs and
      1387 lakes, across the western United States and Canada, to assess differences
      between reservoirs and lakes, as well as the influence of reservoir management on
      fish THg concentrations. Fish THg concentrations were 1.4-fold higher in
      reservoirs (0.13+/-0.011MUg/g wet weight+/-standard error) than lakes (0.09+/
      0.006), though this difference varied among ecoregions. Fish THg concentrations
      were 1.5- to 2.6-fold higher in reservoirs than lakes of the North American
      Deserts, Northern Forests, and Mediterranean California ecoregions, but did not
      differ between reservoirs and lakes in four other ecoregions. Fish THg
      concentrations peaked in three-year-old reservoirs then rapidly declined in 4
      12year old reservoirs. Water management was particularly important in influencing
      fish THg concentrations, which were up to 11-times higher in reservoirs with
      minimum water storage occurring in May, June, or July compared to reservoirs with
      minimum storage occurring in other months. Between-year changes in maximum water
      storage strongly influenced fish THg concentrations, but within-year fluctuations
      in water levels did not influence fish THg concentrations. Specifically, fish THg
      concentrations increased up to 3.2-fold over the range of between-year changes in
      maximum water storage in all ecoregions except Mediterranean California. These
      data highlight the role of reservoir creation and management in influencing fish
      THg concentrations and suggest that water management may provide an effective
      means of mitigating Hg bioaccumulation in some reservoirs. 

PMID- 27039276
TI  - Depression Trajectories of Antenatally Depressed and Nondepressed Young Mothers:
      Implications for Child Socioemotional Development.
AB  - OBJECTIVES: This study explores the longitudinal trajectories of depressive
      symptoms in young mothers and investigate the consequences of maternal depression
      for children's birth outcomes and behavioral adjustment. HYPOTHESIS: Antenatal
      depression puts children of young mothers at risk for adjustment difficulties by
      adversely impacting birth outcomes and maternal symptoms after birth. METHODS:
      Data were drawn from a three-wave randomized, controlled trial of a statewide
      home visiting program for young primiparous women. A subsample of women (n = 400)
      who were prenatal at intake was used in the analysis. Mothers were divided into
      an antenatally depressed group (ADG; 40%) and a healthy group (HG) based on their
      symptoms at intake. Mothers reported depressive symptoms at intake and 12- and 24
      month follow-up, and filled out a checklist of child behavior problems at 24
      months follow-up. Perinatal and birth outcomes were derived from the Electronic
      Birth Certificate collected by the State Department of Public Health at discharge
      from the hospital. RESULTS: ADG and HG had similar pregnancy characteristics and
      birth outcomes, but ADG reported more child behavioral problems. Multigroup
      latent growth curve analysis provided evidence for distinct depression
      trajectories. A mediation hypothesis was not supported. In both groups, steeper
      increase in symptoms over time predicted more mother-reported child behavioral
      problems. CONCLUSIONS: Findings are consistent with studies linking antenatal
      depression with post-birth symptoms, underscoring the importance of prenatal
      screening for depression.

PMID- 27039277
TI  - Secondary Prevention Recommendation Attainment with Cardiac Rehabilitation: Is
      There a Gender Disparity?
AB  - BACKGROUND: Achievement of secondary prevention guideline recommendations (i.e.,
      goals) with cardiac rehabilitation (CR) is not well-documented, especially for
      women. This study examined achievement of the American Heart Association/American
      College of Cardiology (AHA/ACC) goals before and after CR by gender. METHODS: Of
      12,976 patients enrolled in the Wisconsin CR Outcomes Registry, 8,929 (68.8%)
      completed CR and were included in the sample. Attainment of 15 AHA/ACC goals
      before and after CR was examined by extracting corresponding data points in the
      registry as entered by CR program staff. Gender differences in achievement of
      these goals after CR were examined via generalized estimating equations
      technique. RESULTS: Attainment of AHA/ACC goals before CR ranged from 15.3% of
      patients (physical activity) to 98.1% (aspirin), and by 17.6% (physical activity)
      to 98.4% (diastolic blood pressure) by CR completion. Significant improvements
      were achieved for 8 goals (53.3%), ranging from 0.7% for body mass index (BMI) to
      50.8% for physical activity. Women were significantly less likely than men to
      achieve the following goals by CR completion: triglycerides (adjusted odds ratio
      [AOR], 0.54; 95% confidence interval [CI], 0.45-0.66), physical activity (AOR,
      0.66; 95% CI, 0.59-0.74), and hemoglobin A1C (AOR, 0.50; 95% CI, 0.32-0.78).
      Women were significantly more likely than men to achieve the high-density
      lipoprotein goal (AOR, 1.39; 95% CI, 1.05-1.86). There were no gender differences
      in goal achievement for blood pressure, total cholesterol, low-density
      lipoprotein, BMI, smoking cessation, or medication use. More than 94% of patients
      were taking three of four recommended secondary prevention medications both
      before and after the program. CONCLUSIONS: Men and women generally improved
      similarly in terms of AHA/ACC goal achievement. Quality improvement strategies
      need to focus on physical activity and blood glucose control in women.

PMID- 27039279
TI  - Closing the gap: The approach of optical and computational microscopy to uncover
      biomembrane organization.
AB  - Biological membranes are complex composites of lipids, proteins and sugars, which
      catalyze a myriad of vital cellular reactions in a spatiotemporal tightly
      controlled manner. Our understanding of the organization principles of
      biomembranes is limited mainly by the challenge to measure distributions and
      interactions of lipids and proteins within the complex environment of living
      cells. With the recent advent of super-resolution optical microscopy (or
      nanoscopy) one now has approached the molecular scale regime with non-invasive
      live cell fluorescence observation techniques. Since in silico molecular dynamics
      (MD) simulation techniques are also improving to study larger and more complex
      systems we can now start to integrate live-cell and in silico experiments to
      develop a deeper understanding of biomembranes. In this review we summarize
      recent progress to measure lipid-protein interactions in living cells and give
      examples how MD simulations can complement and upgrade the experimental data.
      This article is part of a Special Issue entitled: Biosimulations edited by Ilpo
      Vattulainen and Tomasz Rog.

PMID- 27039278
TI  - Relating structure and internalization for ROMP-based protein mimics.
AB  - Elucidating the predominant cellular entry mechanism for protein transduction
      domains (PTDs) and their synthetic mimics (PTDMs) is a complicated problem that
      continues to be a significant source of debate in the literature. The PTDMs
      reported here provide a well-controlled platform to vary molecular composition
      for structure activity relationship studies to further our understanding of PTDs,
      their non-covalent association with cargo, and their cellular internalization
      pathways. Specifically, several guanidine rich homopolymers, along with an
      amphiphilic block copolymer were used to investigate the relationship between
      structure and internalization activity in HeLa cells, both alone and non
      covalently complexed with EGFP by flow cytometery and confocal imaging. The
      findings indicate that while changing the amount of positive charge on our PTDMs
      does not seem to affect the endosomal uptake, the presence of hydrophobicity
      appears to be a critical factor for the polymers to enter cells either alone, or
      with associated cargo. 

PMID- 27039280
TI  - A chimeric protein of aluminum-activated malate transporter generated from wheat
      and Arabidopsis shows enhanced response to trivalent cations.
AB  - TaALMT1 from wheat (Triticum aestivum) and AtALMT1 from Arabidopsis thaliana
      encode aluminum (Al)-activated malate transporters, which confer acid-soil
      tolerance by releasing malate from roots. Chimeric proteins from TaALMT1 and
      AtALMT1 (Ta::At, At::Ta) were previously analyzed in Xenopus laevis oocytes.
      Those studies showed that Al could activate malate efflux from the Ta::At chimera
      but not from At::Ta. Here, functions of TaALMT1, AtALMT1 and the chimeric protein
      Ta::At were compared in cultured tobacco BY-2 cells. We focused on the
      sensitivity and specificity of their activation by trivalent cations. The
      activation of malate efflux by Al was at least two-fold greater in the chimera
      than the native proteins. All proteins were also activated by lanthanides
      (erbium, ytterbium, gadolinium, and lanthanum), but the chimera again released
      more malate than TaALMT1 or AtALMT1. In Xenopus oocytes, Al, ytterbium, and
      erbium activated inward currents from the native TaALMT1 and the chimeric
      protein, but gadolinium only activated currents from the chimera. Lanthanum
      inhibited currents from both proteins. These results demonstrated that function
      of the chimera protein was altered compared to the native proteins and was more
      responsive to a range of trivalent cations when expressed in plant cells. 

PMID- 27039281
TI  - Lunch-time food choices in preschoolers: Relationships between absolute and
      relative intakes of different food categories, and appetitive characteristics and
      weight.
AB  - Children's appetitive characteristics measured by parent-report questionnaires
      are reliably associated with body weight, as well as behavioral tests of
      appetite, but relatively little is known about relationships with food choice. As
      part of a larger preloading study, we served 4-5year olds from primary school
      classes five school lunches at which they were presented with the same
      standardized multi-item meal. Parents completed Child Eating Behavior
      Questionnaire (CEBQ) sub-scales assessing satiety responsiveness (CEBQ-SR), food
      responsiveness (CEBQ-FR) and enjoyment of food (CEBQ-EF), and children were
      weighed and measured. Despite differing preload conditions, children showed
      remarkable consistency of intake patterns across all five meals with day-to-day
      intra-class correlations in absolute and percentage intake of each food category
      ranging from 0.78 to 0.91. Higher CEBQ-SR was associated with lower mean intake
      of all food categories across all five meals, with the weakest association
      apparent for snack foods. Higher CEBQ-FR was associated with higher intake of
      white bread and fruits and vegetables, and higher CEBQ-EF was associated with
      greater intake of all categories, with the strongest association apparent for
      white bread. Analyses of intake of each food group as a percentage of total
      intake, treated here as an index of the child's choice to consume relatively more
      or relatively less of each different food category when composing their total
      lunch-time meal, further suggested that children who were higher in CEBQ-SR ate
      relatively more snack foods and relatively less fruits and vegetables, while
      children with higher CEBQ-EF ate relatively less snack foods and relatively more
      white bread. Higher absolute intakes of white bread and snack foods were
      associated with higher BMI z score. CEBQ sub-scale associations with food intake
      variables were largely unchanged by controlling for daily metabolic needs.
      However, descriptive comparisons of lunch intakes with expected amounts based on
      metabolic needs suggested that overweight/obese boys were at particularly high
      risk of overeating. Parents' reports of children's appetitive characteristics on
      the CEBQ are associated with differential patterns of food choice as indexed by
      absolute and relative intake of various food categories assessed on multiple
      occasions in a naturalistic, school-based setting, without parents present.

PMID- 27039282
TI  - Trends in the consumption of low-calorie sweeteners.
AB  - Low-calorie sweeteners (LCS) offer a palatable alternative to caloric sugars such
      as sucrose (table sugar) and high fructose corn syrup and are commonly found in
      soft drinks, sweetener packets, grains, snack foods, dairy products, hygiene
      products, and medications. Consumption of LCS has increased significantly in
      recent years and while this trend is expected to continue, controversy exists
      surrounding their use. The purpose of this article is to review trends in the
      consumption of LCS, to summarize differences in LCS consumption across socio
      demographic subgroups and subtypes of LCS-containing products, and to highlight
      important challenges in the accurate assessment of LCS consumption.

PMID- 27039283
TI  - Distinguishing asymptomatic bacteriuria from urinary tract infection in the
      elderly - the use of urine levels of heparin-binding protein and interleukin-6.
AB  - Asymptomatic bacteriuria (ABU) is highly prevalent among elderly patients. It can
      be difficult to distinguish ABU from symptomatic urinary tract infection (UTI) in
      this population, which leads to unnecessary antibiotic treatment. Urinary heparin
      binding protein (U-HBP) and urinary interleukin-6 (U-IL-6) have previously been
      studied as diagnostic markers for UTI. In this study, biomarkers were measured in
      the urine of 134 nursing home residents. The prevalence of ABU in this
      population, excluding patients with urinary catheter, was 32.8%. Levels of U-HBP
      and IL-6 were significantly lower among residents with ABU when compared to 49
      patients with verified UTI. When previously defined cut-off limits were used, U
      HBP had a high negative predictive value for UTI (93%), however, the specificity
      for differentiating patients with UTI and ABU was low. Discriminatory values were
      better for U-IL-6 with a sensitivity of 80% and specificity of 82% for the
      differentiation between the subgroup of pyelonephritis and ABU. 

PMID- 27039285
TI  - Multi-host environments select for host-generalist conjugative plasmids.
AB  - BACKGROUND: Conjugative plasmids play an important role in bacterial evolution by
      transferring ecologically important genes within and between species. A key limit
      on interspecific horizontal gene transfer is plasmid host range. Here, we
      experimentally test the effect of single and multi-host environments on the host
      range evolution of a large conjugative mercury resistance plasmid, pQBR57.
      Specifically, pQBR57 was conjugated between strains of a single host species,
      either P. fluorescens or P. putida, or alternating between P. fluorescens and P.
      putida. Crucially, the bacterial hosts were not permitted to evolve allowing us
      to observe plasmid evolutionary responses in isolation. RESULTS: In all
      treatments plasmids evolved higher conjugation rates over time. Plasmids evolved
      in single-host environments adapted to their host bacterial species becoming less
      costly, but in the case of P. fluorescens-adapted plasmids, became costlier in P.
      putida, suggesting an evolutionary trade-off. When evolved in the multi-host
      environment plasmids adapted to P. fluorescens without a higher cost in P.
      putida. CONCLUSION: Whereas evolution in a single-host environment selected for
      host-specialist plasmids due to a fitness trade-off, this trade-off could be
      circumvented in the multi-host environment, leading to the evolution of host
      generalist plasmids.

PMID- 27039284
TI  - Molecular and proteome analyses highlight the importance of the Cpx envelope
      stress system for acid stress and cell wall stability in Escherichia coli.
AB  - Two-component systems (TCS) play a pivotal role for bacteria in stress regulation
      and adaptation. However, it is not well understood how these systems are
      modulated to meet bacterial demands. Especially, for those TCS using an accessory
      protein to integrate additional signals, no data concerning the role of the
      accessory proteins within the coordination of the response is available. The Cpx
      envelope stress two-component system, composed of the sensor kinase CpxA and the
      response regulator CpxR, is orchestrated by the periplasmic protein CpxP which
      detects misfolded envelope proteins and inhibits the Cpx system in unstressed
      cells. Using selected reaction monitoring, we observed that the amount of CpxA
      and CpxR, as well as their stoichiometry, are only marginally affected, but that
      a 10-fold excess of CpxP over CpxA is needed to switch off the Cpx system.
      Moreover, the relative quantification of the proteome identified not only acid
      stress response as a new indirect target of the Cpx system, but also suggests a
      general function of the Cpx system for cell wall stability.

PMID- 27039286
TI  - The reliability and validity of the Japanese version of the Temperament and
      Personality Questionnaire for patients with non-melancholic depression.
AB  - BACKGROUND: Parker et al. (2006) proposed a new approach to classify specific sub
      types of non-melancholic depression caused by various stress factors and
      premorbid personality styles: the Temperament and Personality Questionnaire
      (T&P). The current study aim was to develop the Japanese version of the T&P and
      evaluate its reliability and validity. METHODS: We studied 114 patients with non
      melancholic depression. Reliability was assessed using the test-retest method.
      Convergent validity of the T&P was compared with the clinician ratings of each
      patient for the eight personality traits. We also assessed the impact of
      depressive state on the T&P. RESULTS: The test-retest intraclass correlation
      coefficients among eight constructs of the T&P ranged from 0.77 to 0.89,
      indicating good-to-excellent reliability. Anxious Worrying (rho=0.29),
      Perfectionism (rho=0.17), Personal Reserve (rho=0.18), Irritability (rho=0.38),
      and Social Avoidance (rho=0.32) showed adequate levels of convergent validity;
      Rejection Sensitivity (rho=0.16), Self-criticism (rho=-0.02), and Self-focus
      (rho=0.07) showed relatively weak convergent validity. Perfectionism (rho=-0.06),
      Social Avoidance (rho=0.17), Anxious Worrying (rho=0.40), Personal Reserve
      (rho=0.30), Irritability (rho=0.28), Rejection Sensitivity (rho=0.35), Self
      criticism (rho=0.49), and Self-focus (rho=0.24) showed minimal sensitivity to
      mood state effects. LIMITATIONS: Only one site was used. While a Likert scale was
      used, the clinician-rated personality trait measure had not been validated.
      CONCLUSIONS: The J-T&P is a reliable and valid measure for assessing temperament
      and personality in Japanese patients with non-melancholic depression.

PMID- 27039287
TI  - [Aorto-bifermoral grafs infection due to Candida parapsilosis. An unusual
      pathogen].
AB  - BACKGROUND: Aorto-enteric fistula is a rare and potentially lethal entity. Its
      presentation may be as an enteric-paraprosthetic fistula, due to injury in the
      gut caused by direct contact with the vascular prosthesis. OBJECTIVE: We report a
      case of enteric-paraprosthetic fistulae with the unusual finding of Candida
      parapsilosis as the only isolated pathogen. CLINICAL CASE: A 65-year-old male,
      smoker, with aortobifemoral revascularisation with dacron due to aortoiliac
      occlusive disease, and re-intervention for thrombosis of left arm at 6 months.
      Hospitalisation at 22 months was required due to a toxic syndrome, which was
      diagnosed as enteric-paraprosthetic fistulae after complementary studies. The
      graft was removed and an extra-anatomic revascularisation was performed.
      Microbiology specimens taken from the duodenal segment in contact with the
      prosthesis showed the prosthetic segment and peri-prosthetic fluid were positive
      to C. parapsilosis. DISCUSSION: The finding of C. parapsilosis in all cultures
      taken during surgery, along with negative blood cultures and no other known
      sources of infection, is of interest. It is an unusual pathogen with low
      virulence and limited as regards other Candida species. Our patient had no
      clinical data common to cases of infection with C. parapsilosis, and the
      mechanism of graft infection is unknown. CONCLUSION: Graft infection by C.
      parapsilosis may be anecdotal. However, its consequences can also be severe.
      Microbiological tests can be useful to adjust antimicrobial therapy in the post
      operative period, but their usefulness for determining the aetiology is doubtful,
      as it may be just an incidental finding.

PMID- 27039288
TI  - [Prognostic factors for survival in patients with resectable advanced gastric
      adenocarcinoma].
AB  - BACKGROUND: Patients under 45 years with gastric cancer are associated with a
      poor prognosis. Recent studies report that the 5-year survival is better in
      younger patients after curative resection. OBJECTIVE: To determine if prognostic
      factors such as age under 45 years old, anaemia, weight loss, tumour
      differentiation, histological sub-type, depth of invasion, and lymph node
      involvement, reduce the survival of patients with resectable advanced gastric
      adenocarcinoma undergoing gastrectomy with limited and extended lymphadenectomy.
      MATERIALS AND METHODS: This study included a cohort of consecutive cases treated
      in the Sarcomas Department of the Oncology Hospital of the Centro Medico Nacional
      Siglo XXI, of the Instituto Mexicano del Seguro Social, during the period between
      January 2000 and December 2006. RESULTS: Of the total of 588 patients evaluated,
      112 (19%) were under 45 years, 43% classified as Borrmann IV, and 36% as Borrmann
      III. Metastatic disease was present in 39.3%, localised diffuse in 12.5%; lower
      resectability 52.7 vs. 61.3% in older than 45 years. At the end of the study
      29.5% of patients under 45 years were alive; no recurrence in 26.8%, with an
      overall survival of 58.6+/-4.3 months, compared with 18.3% of patients alive over
      45 years, 17.9% disease-free, and with overall survival 35.2+/-4.3 months
      resectable disease. CONCLUSIONS: Patients under 45 years have a better survival
      after a two-year disease-free period.

PMID- 27039289
TI  - [Primary posterior perineal hernia associated with dolichocolon].
AB  - BACKGROUND: Primary posterior perineal hernias in men are rare. We report a case
      of this type of hernia associated with dolichocolon, a condition which, to our
      knowledge, has not been reported previously. CLINICAL CASE: A 71-year old male
      presenting with a perineal tumour of 40 years evolution. He had no history of
      perineal surgery or trauma. On physical examination, a lump of 4*3cm was observed
      in the right para-anal region, which increased in volume during the Valsalva
      manoeuvre. Computed tomography showed a defect in the pelvic floor, which was
      reconstructed using a roll of polypropylene mesh in the hernia defect.
      DISCUSSION: The case described is of interest, not only because a perineal hernia
      is a rare clinical entity, but also because repair using a roll of mesh has not
      been reported associated with a dolichocolon, which can be considered a factor
      risk for development. CONCLUSIONS: The surgical approach and repair technique of
      the pelvic floor for perineal hernias should be individualised. The use of mesh
      for reconstruction should always be considered. The presence of dolichocolon can
      contribute to the gradual development of a perineal hernia.

PMID- 27039290
TI  - Effects of mindfulness-based stress reduction for adults with sleep disturbance:
      a protocol for an update of a systematic review and meta-analysis.
AB  - BACKGROUND: Sleep disturbance is a common and significant health problem that has
      been linked to decreased quality of life. Mindfulness-based stress reduction
      (MBSR) can be a potentially effective intervention for insomnia. In previous
      systematic review examining the effects of MBSR for people with sleep
      disturbance, the authors highlighted the need for additional well-designed
      randomized controlled trials (RCTs) to assess the effects of MBSR practice.
      Recently, several RCTs of the effectiveness of MBSR for individuals who have
      difficulties in sleep have been published. Therefore, the aim of this review is
      to update and synthesize evidence on the effects of MBSR for people with sleep
      disturbance or insomnia. METHODS/DESIGN: We will search ovidMEDLINE, ovidEMBASE,
      Allied and Alternative Medicine, PsycINFO, the Cochrane Central Register of
      Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature,
      and four representative Korean electronic databases including KoreaMed, the
      Korean Studies Information Service System, the Korean Medical Database, and the
      National Digital Science Library. Two reviewers will independently screen and
      select relevant studies. The Cochrane Risk of Bias tool will be used to assess
      risk of bias in the included studies. The primary outcomes will be defined as the
      change in sleep quality before and after the intervention as evaluated by the
      polysomnography or self-reported questionnaires such as the Pittsburgh Sleep
      Quality Index. If quantitative synthesis is not appropriate, a descriptive
      analysis might be undertaken. DISCUSSION: Many published primary studies have
      investigated the positive effects of MBSR on sleep quality; however, there are no
      systematic reviews and meta-analyses synthesizing the evidence of up-to-date
      research on the effects of MBSR for sleep problems. The review findings will aid
      the general population and healthcare providers in making informed decisions on
      evidence-based intervention selection for sleep disturbance or insomnia.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015027963 .

PMID- 27039291
TI  - Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle
      Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.
AB  - IMPORTANCE: Muscle-related statin intolerance is reported by 5% to 20% of
      patients. OBJECTIVE: To identify patients with muscle symptoms confirmed by
      statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies,
      ezetimibe and evolocumab. DESIGN, SETTING, AND PARTICIPANTS: Two-stage randomized
      clinical trial including 511 adult patients with uncontrolled low-density
      lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more
      statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover
      procedure with atorvastatin or placebo to identify patients having symptoms only
      with atorvastatin but not placebo. In phase B, after a 2-week washout, patients
      were randomized to ezetimibe or evolocumab for 24 weeks. INTERVENTIONS: Phase A:
      atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous
      evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). MAIN OUTCOME AND
      MEASURES: Coprimary end points were the mean percent change in LDL-C level from
      baseline to the mean of weeks 22 and 24 levels and from baseline to week 24
      levels. RESULTS: Of the 491 patients who entered phase A (mean age, 60.7 [SD,
      10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry
      mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491
      (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199
      entered phase B, along with 19 who proceeded directly to phase B for elevated
      creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab;
      entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24,
      LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7%
      (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was
      103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute
      change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5
      mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, 
      31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95%
      CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of
      weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute
      difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was 
      36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were reported in 28.8%
      of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank
      P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe
      treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%).
      CONCLUSIONS AND RELEVANCE: Among patients with statin intolerance related to
      muscle-related adverse effects, the use of evolocumab compared with ezetimibe
      resulted in a significantly greater reduction in LDL-C levels after 24 weeks.
      Further studies are needed to assess long-term efficacy and safety. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01984424.

PMID- 27039292
TI  - Topographic expression of the Hippo transducers TAZ and YAP in triple-negative
      breast cancer treated with neoadjuvant chemotherapy.
AB  - BACKGROUND: The Hippo signaling acts as a tumor-suppressor pathway that
      negatively regulates TAZ and YAP. Increasing evidence supports the activation of
      TAZ and YAP in breast cancer. Moreover, the Hippo pathway is involved in the
      biology of non-neoplastic cells residing in the tumor microenvironment. On this
      basis, we herein assessed TAZ and YAP in triple-negative breast cancer and its
      surrounding microenvironemnt in order to investigate their impact on pathological
      complete response (pCR) and tumor recurrence. METHODS: Sixty-one triple-negative
      breast cancer patients treated with neoadjuvant chemotherapy were retrospectively
      evaluated. TAZ and YAP were assessed by immunohistochemistry and classified as
      positive or negative according to the percentage of tumor-expressing cells,
      cellular localization, and staining intensity. TAZ and YAP expression was also
      evaluated in non-lymphocytic stromal cells, tumor-infiltrating lymphocytes (TILs)
      and endothelial cells. The Pearson's Chi-squared test of independence was used to
      test the association between TAZ/YAP and clinical-molecular factors. A
      multivariate logistic regression model was generated to identify variables
      impacting pCR. The Kaplan-Meier method and the log-rank test were used for
      estimating and comparing survival curves. Cox proportional regression models were
      built to evaluate the risk of recurrence for the variables considered. Internal
      validation was carried out with a re-sampling without replacement method.
      RESULTS: We did not observe any impact on pCR rate when TAZ and YAP were
      addressed singularly. Conversely, the combined expression of YAP in tumor cells
      and non-lymphocytic stromal cells was an independent predictor of reduced pCR
      rate in the multivariate model (OR 7.13, 95% CI: 1.23-41.41, p = 0.029). Next,
      the combined expression of TAZ and YAP was associated with shorter disease-free
      survival (DFS) in multivariate analysis (HR 3.07, 95% CI: 1.24-7.61, p = 0.016).
      The robustness of these findings were internally validated. CONCLUSIONS: The
      combined expression of YAP in TNBC cells and in the surrounding stroma seems to
      be associated with a decreased likelihood to achieve pCR. Conversely, the
      combined expression of TAZ and YAP in tumor cells conferred poor survival
      outcomes.

PMID- 27039293
TI  - Return-to-activity after anatomical reconstruction of acute high-grade
      acromioclavicular separation.
AB  - BACKGROUND: To evaluate return-to-activity (RtA) after anatomical reconstruction
      of acute high-grade acromioclavicular joint (ACJ) separation. METHODS: A total of
      42 patients with anatomical reconstruction of acute high-grade ACJ-separation
      (Rockwood Type V) were surveyed to determine RtA at a mean 31 months follow-up (f
      u). Sports disciplines, intensity, level of competition, participation in
      overhead and/or contact sports, as well as activity scales (DASH-Sport-Module,
      Tegner Activity Scale) were evaluated. Functional outcome evaluation included
      Constant score and QuickDASH. RESULTS: All patients (42/42) participated in
      sporting activities at f-u. Neither participation in overhead/contact sports, nor
      level of activity declined significantly (n.s.). 62 % (n = 26) of patients
      reported subjective sports specific ACJ integrity to be at least the same as
      prior to the trauma. Sporting intensity (hours/week: 7.3 h to 5.4 h, p = .004)
      and level of competition (p = .02) were reduced. If activity changed, in 50 %
      other reasons but clinical symptoms/impairment were named for modified behavior.
      QuickDASH (mean 6, range 0-54, SD 11) and DASH-Sport-Module (mean 6, range 0-56,
      SD 13) revealed only minor disabilities at f-u. Over time Constant score improved
      significant to an excellent score (mean 94, range 86-100, SD 4; p < .001).
      Functional outcome was not correlated with RtA (n.s.). CONCLUSION: All patients
      participated in sporting activities after anatomical reconstruction of high-grade
      (Rockwood Type V) ACJ-separation. With a high functional outcome there was no
      significant change in activity level (Tegner) and participation in overhead
      and/or contact sports observed. There was no correlation between functional
      outcome and RtA. Limiting, there were alterations in time spent for sporting
      activities and level of competition observed. But in 50 % those were not related
      to ACJ symptoms/impairment. Unrelated to successful re-established integrity and
      function of the ACJ it should be considered that patients decided not return-to
      activity but are very content with the procedure.

PMID- 27039294
TI  - Intensity modulated arc therapy implementation in a three phase adaptive (18)F
      FDG-PET voxel intensity-based planning strategy for head-and-neck cancer.
AB  - BACKGROUND: This study investigates the implementation of a new intensity
      modulated arc therapy (IMAT) class solution in comparison to a 6-static beam step
      and-shoot intensity modulated radiotherapy (s-IMRT) for three-phase adaptive
      (18)F-FDG-PET-voxel-based dose-painting-by-numbers (DPBN) for head-and-neck
      cancer. METHODS: We developed (18)F-FDG-PET-voxel intensity-based IMAT employing
      multiple arcs and compared it to clinically used s-IMRT DPBN. Three IMAT plans
      using (18)F-FDG-PET/CT acquired before treatment (phase I), after 8 fractions
      (phase II) and CT acquired after 18 fractions (phase III) were generated for each
      of 10 patients treated with 3 s-IMRT plans based on the same image sets. Based on
      deformable image registration (ABAS, version 0.41, Elekta CMS Software, Maryland
      Heights, MO), doses of the 3 plans were summed on the pretreatment CT using
      validated in-house developed software. Dosimetric indices in targets and organs
      at-risk (OARs), biologic conformity of treatment plans set at <=5 %, treatment
      quality and efficiency were compared between IMAT and s-IMRT for the whole group
      and for individual patients. RESULTS: Doses to most organs-at-risk (OARs) were
      significantly better in IMAT plans, while target levels were similar for both
      types of plans. On average, IMAT ipsilateral and contralateral parotid mean doses
      were 14.0 % (p = 0.001) and 12.7 % (p < 0.001) lower, respectively. Pharyngeal
      constrictors D50% levels were similar or reduced with up to 54.9 % for IMAT
      compared to s-IMRT for individual patient cases. IMAT significantly improved
      biologic conformity by 2.1 % for treatment phases I and II. 3D phantom
      measurements reported an agreement of >=95 % for 3 % and 3 mm criteria for both
      treatment modalities. IMAT delivery time was significantly shortened on average
      by 41.1 %. CONCLUSIONS: IMAT implementation significantly improved the biologic
      conformity as compared to s-IMRT in adaptive dose-escalated DPBN treatments. The
      better OAR sparing and faster delivery highly improved the treatment efficiency.

PMID- 27039295
TI  - Ethanolic extract of Descurainia sophia seeds sensitizes A549 human lung cancer
      cells to TRAIL cytotoxicity by upregulating death receptors.
AB  - BACKGROUND: Our previous genome-wide gene expression analysis revealed that tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors 4 (DR4)
      and 5 (DR5) are markedly upregulated by the ethanolic extract of D. sohia seeds
      (EEDS) in A549 TRAIL-refractory cancer cells. In the present study, we
      investigated whether the EEDS-mediated upregulation of TRAIL death receptors was
      associated with increased TRAIL-mediated toxicity in A549 cells in vitro.
      METHODS: Cell proliferation and viability were determined by an automatic cell
      counter. Gene silencing was performed by introducing small interfering RNA into
      cells. Expression changes of cellular proteins were determined by western blot
      analysis. Apoptotic cell death was monitored by western blot analysis. Analysis
      of variance followed by the post-hoc Dunnett's test was used to compare the data.
      RESULTS: EEDS treatment increased both mRNA and protein levels of DR4 and DR5 in
      the TRAIL refractory A549 cells. Co-treatment of A549 cells with sub-lethal dose
      of EEDS and recombinant TRAIL increased the apoptotic cell death. Upregulation of
      DR5 by EEDS was mediated by an endoplasmic reticulum stress-induced transcription
      factor, CCAAT/enhancer-binding protein homologous protein (CHOP), and knockdown
      of CHOP expression inhibited EEDS-induced DR5 upregulation and abolished the EEDS
      associated increase in TRAIL toxicity in A549 cells. CONCLUSIONS: EEDS can
      sensitize A549 cells to TRAIL cytotoxicity by upregulation of TRAIL death
      receptors. Our findings suggested that EEDS is a good initial herbal source for
      the development of an anticancer supplement for anticancer therapeutics
      associated with TRAIL.

PMID- 27039297
TI  - Erratum to: Leucine-rich repeat kinase 2 positively regulates inflammation and
      down-regulates NF-kappaB p50 signaling in cultured microglia cells.

PMID- 27039296
TI  - miR-720 is a downstream target of an ADAM8-induced ERK signaling cascade that
      promotes the migratory and invasive phenotype of triple-negative breast cancer
      cells.
AB  - BACKGROUND: ADAM8 (a disintegrin and metalloproteinase 8) protein promotes the
      invasive and metastatic phenotype of triple-negative breast cancer (TNBC) cells.
      High ADAM8 expression in breast cancer patients is an independent predictor of
      poor prognosis. Here, we investigated whether ADAM8 regulates specific miRNAs,
      their roles in aggressive phenotype, and potential use as biomarkers of disease.
      METHODS: Microarray analysis was performed on RNA from MDA-MB-231 cells after
      transient ADAM8 knockdown using TaqMan miRNA cards. Changes in miRNA levels were
      confirmed using two ADAM8 siRNAs in TNBC cell lines. Kinase inhibitors, beta1
      integrin antagonist antibody, and different forms of ADAM8 were employed to
      elucidate the signaling pathway required for miR-720 expression. miR-720 levels
      were modulated using a specific antagomiR or a mimic, and effects on aggressive
      phenotype of TNBC cells were determined using Boyden chamber and 3D-Matrigel
      outgrowth assays. Plasma was isolated from mice before and after implantation of
      MDA-MB-231 cells and analyzed for miR-720 levels. Serum samples of TNBC patients
      were evaluated for their ADAM8 and miR-720 levels. RESULTS: We identified 68
      miRNAs differentially regulated upon ADAM8 knockdown, including decreased levels
      of secreted miR-720. Ectopic overexpression of wild-type ADAM8 or forms that lack
      metalloproteinase activity similarly induced miR-720 levels. The disintegrin and
      cysteine-rich domains of ADAM8 were shown to induce miR-720 via activation of a
      beta1-integrin to ERK signaling cascade. Knockdown of miR-720 led to a
      significant decrease in migratory and invasive abilities of TNBC cells.
      Conversely, miR-720 overexpression rescued these properties. A profound increase
      in plasma levels of miR-720 was detected 7 days after TNBC cell inoculation into
      mouse mammary fat pads when tumors were barely palpable. Concordantly, miR-720
      levels were found to be significantly higher in serum samples of TNBC patients
      with high ADAM8 expression. CONCLUSIONS: We have shown for the first time that
      miR-720 is induced by ADAM8 signaling via ERK and plays an essential role in
      promoting the aggressive phenotype of TNBCs. miR-720 is elevated in serum of
      patients with ADAM8-high TNBC and, in a group with other miRNAs downstream of
      ADAM8, holds promise as a biomarker for early detection of or treatment response
      of ADAM8-positive TNBCs.

PMID- 27039298
TI  - Heart rate time series characteristics for early detection of infections in
      critically ill patients.
AB  - It is difficult to make a distinction between inflammation and infection.
      Therefore, new strategies are required to allow accurate detection of infection.
      Here, we hypothesize that we can distinguish infected from non-infected ICU
      patients based on dynamic features of serum cytokine concentrations and heart
      rate time series. Serum cytokine profiles and heart rate time series of 39
      patients were available for this study. The serum concentration of ten cytokines
      were measured using blood sampled every 10 min between 2100 and 0600 hours. Heart
      rate was recorded every minute. Ten metrics were used to extract features from
      these time series to obtain an accurate classification of infected patients. The
      predictive power of the metrics derived from the heart rate time series was
      investigated using decision tree analysis. Finally, logistic regression methods
      were used to examine whether classification performance improved with inclusion
      of features derived from the cytokine time series. The AUC of a decision tree
      based on two heart rate features was 0.88. The model had good calibration with
      0.09 Hosmer-Lemeshow p value. There was no significant additional value of adding
      static cytokine levels or cytokine time series information to the generated
      decision tree model. The results suggest that heart rate is a better marker for
      infection than information captured by cytokine time series when the exact stage
      of infection is not known. The predictive value of (expensive) biomarkers should
      always be weighed against the routinely monitored data, and such biomarkers have
      to demonstrate added value.

PMID- 27039299
TI  - Validation and reliability of a guideline appraisal mini-checklist for daily
      practice use.
AB  - BACKGROUND: The use of comprehensive instruments for guideline appraisal is time
      consuming and requires highly qualified personnel. Since practicing physicians
      are generally busy, the rapid-assessment Mini-Checklist (MiChe) tool was
      developed to help them evaluate the quality and utility of guidelines quickly.
      The aim of this study was to validate the MiChe in comparison to the AGREE II
      instrument and to determine its reliability as a tool for guideline appraisal.
      METHODS: Ten guidelines that are relevant to general practice and had been
      evaluated by 2 independent reviewers using AGREE II were assessed by 12 GPs using
      the MiChe. The strength of the correlation between average MiChe ratings and
      AGREE II total scores was estimated using Pearson's correlation coefficient.
      Inter-rater reliability for MiChe overall quality ratings and endorsements was
      determined using intra-class correlations (ICC) and Kendall's W for ordinal
      recommendations. To determine the GPs' satisfaction with the MiChe, mean scores
      for the ratings on five questions were computed using a six-point Likert scale.
      RESULTS: The study showed a high level of agreement between MiChe and AGREE II in
      the quality rating of guidelines (Pearson's r = 0.872; P < 0.001). Inter-rater
      reliability for overall MiChe ratings (ICC = 0.755; P < 0.001) and endorsements
      (Kendall's W = 0.73; P < 0.001) were high. The mean time required for guideline
      assessment was less than 15 min und user satisfaction was generally high.
      CONCLUSIONS: The MiChe performed well in comparison to AGREE II and is suitable
      for the rapid evaluation of guideline quality and utility in practice. TRIAL
      REGISTRATION: German Clinical Trials Register: DRKS00007480.

PMID- 27039300
TI  - Text message-based diabetes self-management support (SMS4BG): study protocol for
      a randomised controlled trial.
AB  - BACKGROUND: Addressing the increasing prevalence, and associated disease burden,
      of diabetes is a priority of health services internationally. Interventions to
      support patients to effectively self-manage their condition have the potential to
      reduce the risk of costly and debilitating complications. The utilisation of
      mobile phones to deliver self-management support allows for patient-centred care
      at the frequency and intensity that patients desire from outside the clinic
      environment. Self-Management Support for Blood Glucose (SMS4BG) is a novel text
      message-based intervention for supporting people with diabetes to improve self
      management behaviours and achieve better glycaemic control and is tailored to
      individual patient preferences, demographics, clinical characteristics, and
      culture. This study aims to assess whether SMS4BG can improve glycaemic control
      in adults with poorly controlled diabetes. This paper outlines the rationale and
      methods of the trial. METHODS/DESIGN: A two-arm, parallel, randomised controlled
      trial will be conducted across New Zealand health districts. One thousand
      participants will be randomised at a 1:1 ratio to receive SMS4BG, a theoretically
      based and individually tailored automated text message-based diabetes self
      management support programme (intervention) in addition to usual care, or usual
      care alone (control). The primary outcome is change in glycaemic control (HbA1c)
      at 9 months. Secondary outcomes include glycaemic control at 3 and 6 months, self
      efficacy, self-care behaviours, diabetes distress, health-related quality of
      life, perceived social support, and illness perceptions. Cost information and
      healthcare utilisation will also be collected as well as intervention
      satisfaction and interaction. DISCUSSION: This study will provide information on
      the effectiveness of a text message-based self-management support tool for people
      with diabetes. If found to be effective it has the potential to provide
      individualised support to people with diabetes across New Zealand (and
      internationally), thus extending care outside the clinic environment. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12614001232628 .

PMID- 27039301
TI  - Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and
      FOXP3+ T cells in the inflamed muscle of patients with polymyositis and
      dermatomyositis.
AB  - BACKGROUND: T-cell infiltrates may persist in muscle tissue of polymyositis (PM)
      and dermatomyositis (DM) patients despite aggressive immunosuppressive treatment.
      Here, we investigated to what extent persistent T cells in affected muscle were
      FOXP3+, a marker for regulatory T cells (Tregs), or CD244+, a marker for CD28null
      T cells, and whether their presence correlated to clinical outcome. The
      sensitivity of CD28null T cells towards glucocorticoid and Treg-mediated
      immunosuppression was also investigated. METHODS: Muscle biopsies from 16 newly
      diagnosed or untreated patients with PM/DM were investigated by
      immunohistochemistry for expression of CD3, FOXP3 and CD244 before and after
      treatment with glucocorticoids and immunosuppressive agents. For clinical
      evaluation, serum levels of creatine kinase, muscle performance (FI and MMT8),
      disease activity (MITAX) and disability (HAQ) were measured. In vitro suppressive
      effects of glucocorticoids and Tregs on T-cell activation were measured by CD69
      upregulation. RESULTS: Before treatment, CD244+ cells were present at higher
      proportions compared to FOXP3+ cells in the inflamed muscle. Following treatment,
      FOXP3+ cell numbers decreased while CD244+ cells persisted. Patients with
      impaired muscle function (<75 % FI) post-treatment had higher levels of CD244+
      cells in the follow-up biopsy compared to those with FI >75 %. MITAX and HAQ
      correlated with the number of CD244+ cells post-treatment. CD4+CD28null T cells
      displayed lower sensitivity towards both glucocorticoid and Treg-mediated
      immunosuppression in vitro compared to their CD28+ counterparts. CONCLUSIONS:
      Poor outcome in patients with myositis following immunosuppressive therapy was
      linked to persistence of CD244+ (CD28null) T cells in muscle tissue, suggesting
      their resistance against immunosuppression. A relative loss of regulatory T cells
      could also contribute to poor clinical outcome given their recently ascribed role
      in muscle tissue regeneration.

PMID- 27039302
TI  - Diagnosing onset of labor: a systematic review of definitions in the research
      literature.
AB  - BACKGROUND: The diagnosis of labor onset has been described as one of the most
      important judgments in maternity care. There is compelling evidence that the
      duration of both latent and active phase labor are clinically important and
      require consistent approaches to measurement. In order to measure the duration of
      labor phases systematically, we need standard definitions of their onset. We
      reviewed the literature to examine definitions of labor onset and the evidentiary
      basis provided for these definitions. METHODS: Five electronic databases were
      searched using predefined search terms. We included English, French and German
      language studies published between January 1978 and March 2014 defining the onset
      of latent labor and/or active labor in a population of healthy women with term
      births. Studies focusing exclusively on induced labor were excluded. RESULTS: We
      included 62 studies. Four 'types' of labor onset were defined: latent phase,
      active phase, first stage and unspecified. Labor onset was most commonly defined
      through the presence of regular painful contractions (71% of studies) and/or some
      measure of cervical dilatation (68% of studies). However, there was considerable
      discrepancy about what constituted onset of labor even within 'type' of labor
      onset. The majority of studies did not provide evidentiary support for their
      choice of definition of labor onset. CONCLUSIONS: There is little consensus
      regarding definitions of labor onset in the research literature. In order to
      avoid misdiagnosis of the onset of labor and identify departures from normal
      labor trajectories, a consistent and measurable definition of labor onset for
      each phase and stage is essential. In choosing standard definitions, the
      consequences of their use on rates of maternal and fetal morbidity must also be
      examined.

PMID- 27039303
TI  - Need for streamlined use of DPP-4 inhibitors in the treatment of type 2 diabetes.
AB  - Regulatory agencies request an assessment of cardiovascular safety for all "new"
      oral anti-diabetic drugs in order to avoid possible negative effects on
      cardiovascular events. Dipeptidyl peptidase 4 inhibitors have emerged as a new
      therapeutic alternative for the treatment of type 2 diabetes mellitus, but the
      several large post-marketing clinical trials have shown only a modest effect in
      glycaemic control and, more importantly, a neutral effect on total and
      cardiovascular events. Conversely a recent trial with empagliflozin, a sodium
      glucose co-transporter 2 inhibitor, has shown significant effect on overall and
      cardiovascular mortality. Although glycaemic control is an important aspect of
      diabetes management, the results of the EMPA-REG outcome trial suggest that it is
      possible to develop anti-diabetic drugs that may exert an overall beneficial
      effect beyond the mere improvement of glycaemic control. While the regulatory
      hurdles should not be increased, there is the need for evaluation of the net
      clinical impact and cost effectiveness of all anti-diabetic agents. Therefore, a
      better collaboration among all stakeholders is needed in order to develop studies
      with endpoints that will be both clinically meaningful including appropriate
      follow-up, and economically relevant in patients with type 2 diabetes mellitus. 

PMID- 27039304
TI  - The use and impact of quality of life assessment tools in clinical care settings
      for cancer patients, with a particular emphasis on brain cancer: insights from a
      systematic review and stakeholder consultations.
AB  - PURPOSE: Patient-reported data are playing an increasing role in health care. In
      oncology, data from quality of life (QoL) assessment tools may be particularly
      important for those with limited survival prospects, where treatments aim to
      prolong survival while maintaining or improving QoL. This paper examines the use
      and impact of using QoL measures on health care of cancer patients within a
      clinical setting, particularly those with brain cancer. It also examines
      facilitators and challenges, and provides implications for policy and practice.
      DESIGN: We conducted a systematic literature review, 15 expert interviews and a
      consultation at an international summit. RESULTS: The systematic review found no
      relevant intervention studies specifically in brain cancer patients, and after
      expanding our search to include other cancers, 15 relevant studies were
      identified. The evidence on the effectiveness of using QoL tools was inconsistent
      for patient management, but somewhat more consistent in favour of improving
      patient-physician communication. Interviews identified unharnessed potential and
      growing interest in QoL tool use and associated challenges to address.
      CONCLUSION: Our findings suggest that the use of QoL tools in cancer patients may
      improve patient-physician communication and have the potential to improve care,
      but the tools are not currently widely used in clinical practice (in brain cancer
      nor some other cancer contexts) although they are in clinical trials. There is a
      need for further research and stakeholder engagement on how QoL tools can achieve
      most impact across cancer and patient contexts. There is also a need for policy,
      health professional, research and patient communities to strengthen information
      exchange and debate, support awareness raising and provide training on tool
      design, use and interpretation.

PMID- 27039306
TI  - Prognostic factors in male breast cancer: a population-based study.
AB  - Prognostic factors in male breast cancer (MaBC) are controversial. The objective
      of this study was to analyze patient characteristics and prognostic factors in
      MaBC over the last decade. Using the Surveillance, Epidemiology, and End Results
      program, we extracted MaBC patients diagnosed between 2003 and 2012. Patient
      characteristics were compared between tumor grades. We conducted univariate and
      multivariate analyses to determine the effects of each prognostic variable on
      overall survival (OS). The study included 2992 patients. The majority had ductal
      (85 %), ER-positive (95.1 %), and PR-positive (86 %) breast cancer; however, only
      12.4 % had grade I tumors. Stage I and II disease represented 73 % of cases.
      There was a significant association between grade III/IV tumors with ductal
      histology, ER and PR negativity, advanced stage, receipt of mastectomy and
      radiotherapy, and breast cancer death (all P < 0.05). ER-positive patients had
      better OS (hazard ratio 0.69, P = 0.03); however, after 7.5 years, OS rates by ER
      status were similar. In multivariate analysis, older age, grade III/IV tumors,
      stage IV disease, no surgery, no radiotherapy, ER-negative tumors, and unmarried
      patients had significantly shorter OS (all P < 0.05). Over the past decade, MaBC
      has been diagnosed most frequently with early stages of disease and high rates of
      ER positivity; however, grade I is uncommon. ER positivity is associated with
      better prognosis, mainly during the first 5 years after diagnosis. Age at
      diagnosis, tumor grade, stage, surgery, radiotherapy, ER, and marital status have
      clear impact on OS in MaBC.

PMID- 27039305
TI  - Evaluation of measurement properties of self-administered PROMs aimed at patients
      with non-specific shoulder pain and "activity limitations": a systematic review.
AB  - OBJECTIVE: To critically appraise and compare the measurement properties of self
      administered patient-reported outcome measures (PROMs) focussing on the shoulder,
      assessing "activity limitations." STUDY DESIGN: Systematic review. The study
      population had to consist of patients with shoulder pain. We excluded
      postoperative patients or patients with generic diseases. The methodological
      quality of the selected studies and the results of the measurement properties
      were critically appraised and rated using the COSMIN checklist. RESULTS: Out of a
      total of 3427 unique hits, 31 articles, evaluating 7 different questionnaires,
      were included. The SPADI is the most frequently evaluated PROM and its
      measurement properties seem adequate apart from a lack of information regarding
      its measurement error and content validity. CONCLUSION: For English, Norwegian
      and Turkish users, we recommend to use the SPADI. Dutch users could use either
      the SDQ or the SST. In German, we recommend the DASH. In Tamil, Slovene, Spanish
      and the Danish languages, the evaluated PROMs were not yet of acceptable
      validity. None of these PROMs showed strong positive evidence for all measurement
      properties. We propose to develop a new shoulder PROM focused on activity
      limitations, taking new knowledge and techniques into account.

PMID- 27039307
TI  - Interferon-Gamma Release Assays for the Diagnosis of Tuberculosis: A Systematic
      Review and Meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: We conducted a systematic review and meta-analysis to
      compare the accuracy of the interferon-gamma release assays (IGRAs) and the
      tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis
      infection. METHODS: We systematically searched PubMed, Embase, Cochrane library,
      and Web of Science databases for relevant published studies in recent decades and
      calculated pooled estimated sensitivities, specificities, DOR, and SROC curve of
      the QFT-IT, T-SPOT and TST. Random-effects models were used to assess estimates
      from studies with significant heterogeneity. Moreover, area under the curve was
      used to evaluate the accuracy of the tests. RESULTS: Overall, 9 studies for QFT
      IT, 12 studies for T-SPOT, and 16 studies for TST involving 3586 participants
      were included in this analysis. We found that sensitivities of the QFT-IT, T
      SPOT, and TST were respectively 0.842 (95 % CI 0.811-0.870), 0.840 (95 % CI 0.814
      0.864), and 0.665 (CI 0.635-0.693); specificities were respectively 0.745 (95 %
      CI 0.715-0.775), 0.658 (95 % CI 0.621-0.693), and 0.633 (CI 0.605-0.661);
      positive likelihood ratios were respectively 3.652 (95 % CI 2.180-6.117), 2.196
      (95 % CI 1.727-2.794), and 1.825 (95 % CI 1.351-2.464); negative likelihood
      ratios were respectively 0.212 (95 % CI 0.109-0.414), 0.246 (95 % CI 0.161
      0.377), and 0.556 (95 % CI 0.385-0.804); the SROC curves were 19.205, 10.397, and
      3.810. CONCLUSIONS: The two IGRAs showed better performance than TST for the
      diagnosis of the tuberculosis. However, neither of them showed stability in the
      diagnosis of TB.

PMID- 27039310
TI  - What can we offer to 3 million MDRTB household contacts in 2016?
AB  - The diagnosis of multidrug resistant tuberculosis (MDR-TB) in any individual is
      the beginning of a prolonged and difficult therapeutic journey. It also marks the
      moment from which to begin consideration of how to manage close contacts.
      Preventive therapy for drug-susceptible latent tuberculosis infection has been
      demonstrated to be effective at reducing the risk of future disease; the stakes
      are higher when considering prevention of MDR-TB because treatment of active
      disease is more prolonged and toxic and much less effective. This has encouraged
      exploration of the potential utility of preventive therapy, with second-line
      agents, in reducing future incident drug-resistant TB.Three clinical trials of
      preventive therapy for contacts of patients with MDR-TB are starting in 2015/16;
      results will not be available until at least 2020, so what should be offered to
      exposed contacts in the interim?A recent policy brief, arising from a global
      consultation meeting of international experts, recommended preventive therapy
      based upon very limited available observational data. However the many known
      unknowns associated with this approach, include the high proportion of index
      contact pairs with discordant drug susceptibility profiles and (even if
      susceptibilities are shared) the lack of data supporting the use of the selected
      agents in the treatment of latent infection (rather than active disease).It is
      important to acknowledge that the alternative to offering preventive therapy is
      not doing nothing. On the contrary, identified contacts should be maintained
      under close, active surveillance for 24 months, enabling early detection of
      active disease in the small proportion amongst whom this may occur. Such patients
      should benefit from less extensive disease at diagnosis and early access to
      individualized therapeutic regimens with improved treatment outcomes. Moreover
      the vast majority of contacts that do not develop disease will benefit from
      avoidance of potentially toxic, unnecessary therapy.Whether preventive therapy or
      close observation are implemented, national programmes should maintain a register
      of all contacts, interventions and 24 month outcomes; these will provide
      important performance metrics for programmatic management of MDRTB. If harmonized
      and standardized internationally, such a register could rapidly yield a wealth of
      observational data, to complement the trial results of the future.

PMID- 27039309
TI  - Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse
      Hippocampus: Involvement of System [Formula: see text], System [Formula: see
      text], MRP-1, and Nrf2.
AB  - Realgar, a type of mineral drug-containing arsenic, exhibits neurotoxicity. Brain
      glutathione (GSH) is crucial to protect the nervous system and to resist arsenic
      toxicity. Therefore, the main aim of this study was to explore the neurotoxic
      mechanisms of realgar and the protective effects of glycyrrhetinic acid (GA) by
      observing the effects of GA on the hippocampal GSH biosynthetic pathway after
      exposure to realgar. Institute of Cancer Research (ICR) mice were randomly
      divided into five groups: a control group, a GA control group, a realgar alone
      group, a low-dose GA intervention group, and a high-dose GA intervention group.
      Cognitive ability was tested using an object recognition task (ORT). The
      ultrastructures of the hippocampal neurons and synapses were observed. mRNA and
      protein levels of EAAT1, EAAT2, EAAT3, xCT, Nrf2, HO-1, gamma-GCS (GCLC, GCLM),
      and MRP-1 were measured, as was the cellular localization of EAAT3, xCT, MRP-1,
      and Nrf2. The levels of GSH in the hippocampus, the levels of glutamate (Glu) and
      cysteine (Cys) in the extracellular fluid of hippocampal CA1 region, and the
      levels of active sulfur in the brain were also investigated. The results indicate
      that realgar lowered hippocampal GSH levels, resulting in ultrastructural changes
      in hippocampal neurons and synapses and deficiencies in cognitive ability,
      ultimately inducing neurotoxicity. GA could trigger the expression of Nrf2, HO-1,
      EAAT1, EAAT2, EAAT3, xCT, MRP-1, GCLC, and GCLM. Additionally, the expression of
      gamma-GT and the supply levels of Glu and Cys increased, ultimately causing a
      significant increase in hippocampal GSH to alleviate realgar-induced
      neurotoxicity. In conclusion, the findings from our study indicate that GA can
      antagonize decreased brain GSH levels induced by realgar and can lessen the
      neurotoxicity of realgar.

PMID- 27039311
TI  - Models for the red blood cell lifespan.
AB  - The lifespan of red blood cells (RBCs) plays an important role in the study and
      interpretation of various clinical conditions. Yet, confusion about the meanings
      of fundamental terms related to cell survival and their quantification still
      exists in the literature. To address these issues, we started from a
      compartmental model of RBC populations based on an arbitrary full lifespan
      distribution, carefully defined the residual lifespan, current age, and excess
      lifespan of the RBC population, and then derived the distributions of these
      parameters. For a set of residual survival data from biotin-labeled RBCs, we fit
      models based on Weibull, gamma, and lognormal distributions, using nonlinear
      mixed effects modeling and parametric bootstrapping. From the estimated Weibull,
      gamma, and lognormal parameters we computed the respective population mean full
      lifespans (95 % confidence interval): 115.60 (109.17-121.66), 116.71 (110.81
      122.51), and 116.79 (111.23-122.75) days together with the standard deviations of
      the full lifespans: 24.77 (20.82-28.81), 24.30 (20.53-28.33), and 24.19 (20.43
      27.73). We then estimated the 95th percentiles of the lifespan distributions (a
      surrogate for the maximum lifespan): 153.95 (150.02-158.36), 159.51 (155.09
      164.00), and 160.40 (156.00-165.58) days, the mean current ages (or the mean
      residual lifespans): 60.45 (58.18-62.85), 60.82 (58.77-63.33), and 57.26 (54.33
      60.61) days, and the residual half-lives: 57.97 (54.96-60.90), 58.36 (55.45
      61.26), and 58.40 (55.62-61.37) days, for the Weibull, gamma, and lognormal
      models respectively. Corresponding estimates were obtained for the individual
      subjects. The three models provide equally excellent goodness-of-fit, reliable
      estimation, and physiologically plausible values of the directly interpretable
      RBC survival parameters.

PMID- 27039312
TI  - Increased levels of N(epsilon)- Carboxy methyl lysine (N(epsilon)-CML) are
      associated with topographic alterations in retinal pigment epithelium: A
      preliminary study.
AB  - PURPOSE: To evaluate the association of serum levels of N(epsilon)- Carboxy
      methyl lysine (N(epsilon)-CML), an advanced glycation end product with
      topographic alterations in retinal pigment epithelium (RPE) in diabetic
      retinopathy on spectral domain optical coherence tomography (SD-OCT). METHOD:
      Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non
      proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy
      (n=20) and healthy controls (n=20) between the ages of 40 and 65years were
      included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No
      RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE
      alterations in more than two quadrants. Serum level of N(epsilon)-CML and
      glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical
      analysis was done. RESULTS: Significant increase in N(epsilon)-CML was observed
      with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact
      test revealed significant increase in grades of RPE alterations with increased
      severity of diabetic retinopathy (p<0.001). Univariate ordinal regression
      analysis was done to calculate the risk of progression in grades of RPE
      alteration with individual changes in variables like duration of diabetes (odds
      ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nepsilon-CML (odds
      ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting
      progression in grades of RPE alteration revealed Nepsilon-CML to be an
      independent predictor of increase in grades of RPE alteration (adjusted odds
      ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant.
      CONCLUSION: Increase in serum levels of N(epsilon)- Carboxy methyl lysine is
      significantly associated with topographic alterations in RPE. Grades of RPE
      alteration increase significantly with increased severity of diabetic
      retinopathy.

PMID- 27039308
TI  - Brain Iron Metabolism Dysfunction in Parkinson's Disease.
AB  - Dysfunction of iron metabolism, which includes its uptake, storage, and release,
      plays a key role in neurodegenerative disorders, including Parkinson's disease
      (PD), Alzheimer's disease, and Huntington's disease. Understanding how iron
      accumulates in the substantia nigra (SN) and why it specifically targets
      dopaminergic (DAergic) neurons is particularly warranted for PD, as this
      knowledge may provide new therapeutic avenues for a more targeted
      neurotherapeutic strategy for this disease. In this review, we begin with a brief
      introduction describing brain iron metabolism and its regulation. We then provide
      a detailed description of how iron accumulates specifically in the SN and why
      DAergic neurons are especially vulnerable to iron in PD. Furthermore, we focus on
      the possible mechanisms involved in iron-induced cell death of DAergic neurons in
      the SN. Finally, we present evidence in support that iron chelation represents a
      plausable therapeutic strategy for PD.

PMID- 27039313
TI  - A comparison of the Dobbs method for correction of idiopathic and teratological
      congenital vertical talus.
AB  - INTRODUCTION: Congenital vertical talus (CVT) is a rare deformity. Traditionally,
      CVT correction involved extensive soft tissue releases, and this was associated
      with high complication rates. The Dobbs method is less invasive and comprises
      serial manipulation and casting, followed by minimally invasive reduction and K
      wire fixation of the talonavicular joint and percutaneous Achilles tenotomy. AIM:
      The purpose of our study was to compare the outcomes of using the Dobbs method
      for CVT correction in idiopathic and teratological patients. METHODS: A
      retrospective analysis of all patients treated with the Dobbs method for CVT
      between the years 2007 and 2012 was carried out. Notes, electronic records and
      radiographs were reviewed for every patient. The Oxford ankle foot score was
      obtained at follow-up. RESULTS: There was a total of ten children with 18
      affected feet. Five children (ten feet) had teratological CVT. Recurrence was
      noted in six feet (two from the idiopathic group and four from the teratological
      group). The median age was 5 months (range 2-8 months). The mean follow-up was 53
      months (range 24-80 months). There was a significant difference between pre
      operative to initial post-operative and pre-operative to latest follow-up
      measurements for all angles in the successfully treated CVT group (p < 0.000001).
      The mean Oxford ankle foot scores for each domain in all patients are 59.9
      (physical), 88.8 (school and play) and 99.1 (emotional). CONCLUSION: The Dobbs
      method is a less invasive technique of CVT correction. It is an effective initial
      method of treatment in both teratological and idiopathic patients. A higher
      recurrence rate was observed in the teratological group, although this was not
      statistically significant.

PMID- 27039314
TI  - The efficacy of an extended scope physiotherapy clinic in paediatric
      orthopaedics.
AB  - BACKGROUND: The demand for paediatric orthopaedic care is growing, and providing
      the service required is an increasingly challenging task. Physiotherapist-led
      triage clinics are utilised in adult orthopaedics to enable the provision of care
      to patients who may not require a surgical consult. The Physiotherapy Orthopaedic
      Triage Clinic (POTC) was established in Our Lady's Children's Hospital Crumlin in
      response to increasing demands on the paediatric orthopaedic service. The clinic
      is run by physiotherapists working in an advanced practice role (APP), and is the
      first paediatric clinic of its type and scale in the Republic of Ireland.
      PURPOSE: To evaluate the efficacy of the service over the 3-year period from
      January 2011 to December 2013. METHODS: A review of the prospectively gathered
      database was performed in order to establish the demographic profile of patients,
      investigate clinic outcomes, and evaluate the reduction in patient waiting times.
      RESULTS: 2650 patients were managed by the clinic over the 3-year period. A total
      of 77 % of patients were managed without consultant intervention. Fifty-three
      percent of patients were diagnosed as having a normal presentation. The mean
      waiting time reduced from 101.9 weeks pre-2010 to 15.4 weeks in 2013 for those
      patients managed by the POTC. CONCLUSION: Since its inception, the clinic has
      significantly reduced waiting times for routine elective paediatric orthopaedic
      patients while managing the majority of patients independent of surgical opinion.
      This study shows that the APP can deliver high-quality care in the paediatric
      orthopaedic setting, benefitting both patients and service.

PMID- 27039315
TI  - Partial or non-union after triple arthrodesis in children: does it really matter?
AB  - PURPOSE: Triple arthrodesis is a commonly performed salvage procedure to correct
      hindfoot deformity. Non-union is considered an undesirable radiographic outcome;
      however, the clinical ramifications of this are not as well defined. The purpose
      of this study was to determine the incidence of partial or complete radiographic
      non-union after triple arthrodesis in children and characterize the clinical
      consequences. METHODS: An IRB-approved retrospective review of triple arthrodesis
      surgeries in patients less than 16 years of age performed by a single surgeon
      (DSW) identified 159 cases meeting the inclusion criteria. Plain radiographs were
      reviewed for bony fusion (defined as over 80 % radiographic bony union of the
      subtalar, calcaneocuboid, and talonavicular bones) and charts for clinical
      outcomes (pain, return to activity, and subsequent hindfoot surgeries).
      Statistics were used to compare the fused and unfused cases, with p < 0.05
      considered to be significant. RESULTS: Of the 159 cases included in the study, 9
      % did not achieve at least 80 % plain film radiographic union. The fused and
      unfused groups had similar clinical outcomes. Only one patient required surgery
      for sequelae of symptoms arising from a pseudoarthrosis related to the triple
      arthrodesis. The fused and unfused groups were similar in terms of gender and pin
      removal time, but differed significantly in surgical age and underlying
      diagnosis. CONCLUSIONS: This is one of the largest case series of pediatric
      triple arthrodesis surgery presented in the literature. This study demonstrated
      that good clinical outcomes can be achieved despite the lack of radiographic
      union after triple arthrodesis surgery in children. LEVEL OF EVIDENCE: IV.

PMID- 27039316
TI  - Evaluation of immunogenicity and protective efficacy of combination heat-killed
      immunogens from three entero-invasive bacteria in rabbit model.
AB  - Diarrhea is a very common health problem in both developing and developed
      countries. Among the major entero-invasive bacteria, Shigella, Salmonella and
      Campylobacter cause serious problems in different geographic regions. Recently we
      have shown immunogenicity and protective efficacy of heat killed multi-serotype
      Shigella immunogen in different animal models. In our present study, we have
      advanced our research by preparing a combination heat-killed immunogen of three
      different entero-invasive bacteria, Shigella, Salmonella and Campylobacter. After
      three doses on 0th, 14th and 28th day of oral immunization with tri-valent heat
      killed (TVHK) immunogen in rabbit model, the immunogenicity was determined by
      differential count of white blood cells and immunoglobulin assay at various time
      points. During oral immunization differential count of lymphocytes increased
      where as polymorphonuclear leucocytes (PMN) count decreased. Serum IgG and IgA
      showed significant elevation during oral immunization and remained at a
      detectable value upto 120 days. Protection study was performed in both, in vitro
      and in vivo conditions, using bacteriocidal assay and rabbit ligated ileal loop
      model, respectively, which conferred protection against homologous bacteria.
      Moreover, immunoblot assay against whole cell lysate and lipopolysaccharide
      exhibited significant amount of antigen-specific immunoglobulins raised against
      three different bacteria which proved that proteins along with
      lipopolysaccharides played a pivotal role in immunogenicity and protective
      efficacy. This trivalent heat-killed immunogen could be a low-cost, simple, oral,
      non-living vaccine candidate for future use against invasive diarrhea.

PMID- 27039317
TI  - Acute gastrointestinal vaso-occlusive ischemia in sickle cell disease: CT imaging
      features and clinical outcome.
AB  - PURPOSE: The purpose of this study was to determine the incidence, specific
      imaging features, and outcome of gastrointestinal vaso-occlusive ischemia (GVOI)
      in sickle cell patients undergoing CT for acute abdominal pain. METHODS: This
      HIPAA-compliant, IRB-approved retrospective study evaluated sickle cell patients
      with an abdominal pain crisis and acute gastrointestinal abnormalities on CT from
      1/2006 to 1/2014. CT findings were divided into those compatible and incompatible
      with bowel ischemia or clinical diagnosis of GVOI. Two abdominal radiologists (1,
      13 years' experience) reviewed the CTs for specific imaging features of ischemia.
      Clinical laboratory values (lactate, WBC) and outcome were recorded. Descriptive
      statistics and Wilcoxon-Mann-Whitney two-sample rank-sum test were performed.
      RESULTS: Of 217 CTs, 33 had acute gastrointestinal abnormalities: 75% (25/33)
      consistent with ischemia and clinical GVOI. Complications of ischemia occurred in
      16% (4/25): ileus (50%), perforation (25%), and pneumatosis (25%). In
      uncomplicated cases, all had bowel wall thickening: segmental 52% (11/21) or
      diffuse 48% (10/21). The colon was commonly involved (76%, 16/21), particularly
      the ascending (57%, 12/21). Most abnormalities (52%, 11/21) were in the superior
      mesenteric artery distribution. Average lactate (4.3 +/- 4.0 mmol/L, p = 0.02)
      and WBC count (20.1 +/- 10.4, *1000 cells/MUL, p = 0.01) were significantly
      higher in GVOI. Overall mortality in patients with GVOI was 17% (3/18).
      CONCLUSION: GVOI is an important feature of the acute abdominal crisis in
      patients with sickle cell disease and can be seen in up to 75% of patients with
      abnormal bowel findings on CT. The diagnosis should be strongly considered in
      sickle cell patients with CT findings of diffuse or segmental bowel wall
      thickening, particularly involving the colon.

PMID- 27039318
TI  - Subtypes and clinical significance of common bile duct varices in portal vein
      thrombosis: diagnosis and follow-up by Doppler US and EUS.
AB  - PURPOSE: To investigate (1) diagnostic performance of transabdominal color
      doppler ultrasound (US) and endoscopic ultrasound (EUS) for detection and sub
      classification of common bile duct varices (CBDV) in patients with portal vein
      thrombosis (PVT), and (2) clinical significance and natural history of CBDV
      subtypes. PATIENTS AND METHODS: During a 4-year period, 56 patients with PVT
      underwent US and EUS for the presence and subtypes of CBDV. Natural history was
      analyzed for patients who attended control visits. RESULTS: CBDV were diagnosed
      in 57 and 59 % of patients with US and EUS, respectively. In 19 % of patients,
      EUS revealed different CBDV subtypes than previously seen by US. The most common
      were paracholedochal (PCV), while the least common were epicholedochal (ECV) and
      Submucosal varices (SMV). Nine patients had obstructive jaundice and underwent
      ERCP which was complicated by hemobilia in two patients with SMV. Among eight
      patients who underwent control EUS (median follow-up 60 months), the form of CBDV
      remained unchanged. Two patients bled from esophageal varices, both with ECV.
      CONCLUSION: While abdominal US and EUS are equally sensitive for detection of
      CBDV, EUS allows more precise determination of CBDV subtype. Patients with SMV
      might be at increased risk of bleeding upon ERCP.

PMID- 27039319
TI  - Added value of diffusion-weighted imaging to MR cholangiopancreatography for the
      diagnosis of bile duct dilatations.
AB  - PURPOSE: To investigate the added value of diffusion-weighted imaging (DWI) when
      used with conventional T2-weighted magnetic resonance (MR) imaging (T2WI) and MR
      cholangiopancreatography (MRCP) for diagnosing bile duct dilatations. METHODS:
      Our institutional review board approved this retrospective study protocol and
      waived the informed consent requirement. The study included 151 consecutive
      patients (70 men, 81 women) with intra- and/or extra-hepatic bile duct dilatation
      examined using MR imaging. Two radiologists independently and randomly reviewed 3
      image sets (A: MRCP and T2WI; B: DWI; and C: combined T2WI, MRCP, and DWI) at
      different occasions to differentiate between malignancy, biliary lithiasis, and
      benign dilatation. The sensitivity, specificity, and diagnostic accuracy of these
      imaging sets were calculated and compared. RESULTS: For both readers, combined
      T2WI, MRCP, and DWI exhibited significantly higher sensitivity and diagnostic
      accuracy for malignant dilatation, compared with conventional T2WI and MRCP (P <
      0.01 for both readers). However, DWI did not significantly affect the sensitivity
      and diagnostic accuracy for biliary lithiasis or benign dilatation. CONCLUSION:
      The addition of DWI to T2WI and MRCP sequences yields significantly higher
      sensitivity and diagnostic accuracy when examining bile duct dilatations,
      particularly malignant dilatations.

PMID- 27039320
TI  - Liver detection algorithm: its efficacy for CT noise reduction in the liver.
AB  - OBJECTIVES: This study was performed to evaluate the efficacy of a novel computed
      tomography (CT) liver detection algorithm (LDA), which allows for targeted
      increase of radiation dose to the upper abdomen, on image quality of the liver.
      METHODS: We retrospectively evaluated the LDA by comparing 40 consecutive
      patients who had portal venous CT abdomen performed without use of the algorithm,
      to 40 patients in whom the algorithm was used. Image quality was assessed
      objectively by comparing the standard deviation (SD) of attenuation values in
      Hounsfield units (HU) of the abdominal organs. Qualitative analysis was performed
      by two blinded radiologists who independently graded the image quality of
      abdominal organs RESULTS: There was significant noise reduction in the liver (P <
      0.001) and spleen (P < 0.001) in the LDA group compared to the conventional
      group. There was also a significant improvement in image quality of the liver (P
      < 0.001), kidney (P < 0.001), spleen (P < 0.001), pancreas (P < 0.001), and psoas
      (P = 0.005) in the LDA group compared to the conventional group. Overall dose
      between the two groups was similar. CONCLUSIONS: This liver detection algorithm
      improves the subjective image quality of upper abdominal organs, in particular
      the liver, without increasing overall radiation dose.

PMID- 27039321
TI  - Measurement of pancreatic cystic lesions on magnetic resonance imaging: efficacy
      of standards in reducing inter-observer variability.
AB  - PURPOSE: The purpose of this study is to assess inter-observer variability in the
      measurement of pancreatic cystic lesions with MRI and to determine the impact of
      measurement standards. MATERIALS AND METHODS: In this IRB-approved, HIPAA
      compliant study with waiver of informed consent, 144 MRI examinations, containing
      pancreatic cystic lesions measuring between 5 and 35 mm, were reviewed
      independently by two radiology attendings and two abdominal imaging fellows.
      Measurements were repeated by the same reviewers 12 weeks later after the
      introduction of measurement standards. Results were analyzed using within-subject
      standard deviation, intraclass correlation coefficient, and kappa. RESULTS: Prior
      to standardization, the within-subject standard deviation, showing measurement
      variability in each cyst, was 4.0 mm, which was reduced to 3.3 mm after
      introduction of measurement standards (p < 0.01). Overall inter-observer
      agreement, kappa, improved from 0.59 to 0.65 (p = 0.04). The frequency of all
      four reviewers agreeing on size category increased from 51% to 60%. The
      intraclass correlation coefficient increased from 0.81 to 0.86. CONCLUSIONS:
      There is significant and frequent inter-observer variability in the measurement
      of pancreatic cystic lesions with MRI which could affect clinical management.
      Implementation of measurement standards reduces measurement variability and aids
      in preventing erroneous reporting of growth and potentially unwarranted changes
      in management.

PMID- 27039322
TI  - Adenosquamous carcinoma of pancreas: CT and MR imaging features in eight
      patients, with pathologic correlations and comparison with adenocarcinoma of
      pancreas.
AB  - PURPOSE: To reveal the CT and MR imaging features of adenosquamous carcinoma of
      pancreas (ASqC) in eight patients. METHODS: This study was approved by our
      institutional review board. Eight patients with ASqC were included in this study.
      Radiologic and pathologic findings were reviewed in each lesion. Additionally,
      radiologic imaging findings were compared between ASqC and controlled
      adenocarcinoma groups. RESULTS: Significant differences between ASqC and
      adenocarcinoma groups were noted in lesion shape, enhancement pattern on dynamic
      CT images, the presence or absence of necrosis, and tumor thrombus in the portal
      vein (PV) system. Compared with adenocarcinoma, ASqC tended to be round-lobulated
      shape (100% vs. 57.6%), have necrotic portions (100% vs. 39.4%), and have tumor
      thrombus in the PV system (37.5% vs. 6.1%). Extensive central necrosis was found
      in six (75%) of ASqC lesions. More lesions in ASqC group (62.5% vs. 12.1%) showed
      the highest absolute attenuation on pancreatic arterial phase (PAP) or portal
      venous phase (PVP) images, although the average attenuation values of all ASqC
      lesions on PAP, PVP, and delayed phase images were almost the same. Five (83.3%)
      of six resected lesions appeared as nodular type macroscopically.
      Microscopically, all lesions did not show infiltrating growth pattern, but showed
      an intermediate growth pattern, and were surrounded incompletely by fibrous
      tissue. CONCLUSIONS: ASqC tended to be a round-lobulated lesion with extensive
      central necrosis. Additionally, tumor thrombus in the PV system was often
      present. These CT and MR imaging features could be a useful clue for diagnosing
      ASqC.

PMID- 27039323
TI  - Comparison of 11C-4DST and 18F-FDG PET/CT imaging for advanced renal cell
      carcinoma: preliminary study.
AB  - PURPOSE: 4'-[Methyl-(11)C]-thiothymidine (4DST) has been developed as an in vivo
      cell proliferation marker based on its DNA incorporation mechanism. This study
      evaluated the potential of 4DST PET/CT for imaging cellular proliferation in
      advanced clear cell renal cell carcinoma (RCC), compared with FDG PET/CT. Both
      4DST and FDG uptake were compared with biological findings based on surgical
      pathology. METHODS: Five patients (3 men and 2 women; mean (+/-SD) age 64.8 +/-
      11.0 years) with a single RCC (mean diameter: 9.3 +/- 3.2 cm) were examined by
      PET/CT using 4DST and FDG. The dynamic emission scan of 4DST for RCC over 35 min
      followed by a static emission scan of the body for 4DST and FDG. Then we compared
      the maximum standardized uptake value (SUVmax) of 20 areas of RCC on both 4DST
      and FDG images with (1) the Ki-67 index of cellular proliferation (2) Fuhrman
      grade system for nuclear grade (G) in RCC and (3) pathological phosphorylated
      grade of mammalian target of rapamycin (pmTOR). RESULTS: All patient cases showed
      clear uptake of FDG and 4DST in RCC tumors, with mean 4DST SUVmax of 7.3 +/- 2.2
      (range 4.3-9.4) and mean FDG SUVmax of 6.0 +/- 2.8 (range 3.4-10.4). The
      correlation coefficient between SUVmax and Ki-67 index was higher with 4DST (r =
      0.61) than with FDG (r = 0.43). Tumor 4DST uptake (G0: 1.4, G2: 2.6, G2 5.6, G4:
      5.7) and tumor FDG uptake (G0: 1.8, G2: 2.9, G2 3.7, G4: 4.1) were both related
      to Fuhrman grade system. The 4DST uptake increased as the pmTOR grade increases
      (G0: 3.1, G1: 4.8, G2: 4.7, G3: 6.2); in contrast FDG uptake was unrelated to
      pmTOR grade (G0: 2.8, G2: 4.0, G2 3.3, G4: 3.6). CONCLUSION: A higher correlation
      with the proliferation of RCC was observed for 4DST than for FDG. The 4DST uptake
      exhibits the possibility to predict pmTOR grade, indicating that 4DST has
      potential for the evaluation of therapeutic effect with mTOR inhibitor in
      patients with RCC.

PMID- 27039324
TI  - Acute pyelonephritis in transplanted kidneys: can diffusion-weighted magnetic
      resonance imaging be useful for diagnosis and follow-up?
AB  - PURPOSE: To assess reliability of diffusion-weighted magnetic resonance imaging
      (DW-MRI) in the management of acute pyelonephritis (APN) foci in transplanted
      kidneys. MATERIALS AND METHODS: In the 2012-2014 period, 24 kidney-transplanted
      patients underwent MR screening for clinical suspicion of APN. Two readers
      independently analyzed all images, establishing presence and location of APN
      foci. The 22 patients who were positive at the MR exam constituted the study
      population. For each patient the apparent diffusion coefficient (ADC) was
      measured in the APN foci and in three sites of the healthy parenchyma (case
      control comparison). The data were matched to the laboratory measurements for
      white blood cell, C-reactive protein, and serum creatinine. RESULTS: Forty-six
      APN foci were found in 22/24 patients. At the acute stage, the difference in ADC
      between healthy parenchyma and APN foci was significant (2.06 +/- 0.16 vs. 1.43
      +/- 0.32 * 10(-3) mm(2)/s; p < 0.0001). The performance of ADC as APN indicator
      was tested by the receiving operating characteristics (ROC) curve: the area under
      curve AUC = 0.99 witnessed an excellent discriminatory ability, with threshold
      APN/normal parenchyma 1.9 * 10(-3) mm(2)/s. At the 1-month follow-up 43/46 APN
      foci were no longer visible, with ADC values significantly higher than at the
      acute stage; all laboratory data were physiological, with WBC significantly
      reduced from the acute phase (5.2 +/- 1.6 * 10(9)/L vs. 10.6 +/- 4.8 * 10(9)/L; p
      < 0.0001). The other 3 patients underwent further therapy and exams, including a
      third MR. CONCLUSIONS: DW-MRI with ADC measurement seems to be a reliable tool in
      diagnosing and monitoring APN foci in transplanted kidneys, with clinical impact
      on patient management.

PMID- 27039325
TI  - Ultrasound-guided percutaneous ethanol ablation for primary non-parasitic splenic
      cysts in 15 patients.
AB  - PURPOSE: This study aimed to evaluate the feasibility, safety, and efficacy of
      ultrasound (US)-guided percutaneous ethanol ablation (PEA) for primary non
      parasitic splenic cysts. MATERIALS AND METHODS: Between February 2006 and
      February 2015, 15 patients (4 men and 11 women; mean age, 33 +/- 15.3 years; age
      range, 17-65 years) with primary non-parasitic splenic cysts were treated with US
      guided PEA. 99.5% absolute ethanol in an amount of approximately 50%-100% of the
      aspirated volume was injected into each cyst and no more than 240 mL. Standard
      laboratory tests (hemogram, coagulation, serum, and biochemical tumor marker
      levels) were performed before and after PEA. RESULTS: The median follow-up time
      was 18.7 months (range 2.8-59.2 months). During follow-up, seven cysts after
      treatment had disappeared completely, while the other eight cysts had decreased
      significantly in size. The 3-, 6-, 12-, and 24-month volume reduction rates were
      49.7%, 87.6%, 94.3%, and 96.7%. Serum tumor marker CA19-9 levels significantly
      decreased. Mild adverse reactions included moderate pain in four (26.7%),
      unbearable pain in one (6.67%), fever in two (13.3%) and slight intracystic
      bleeding in one (6.67%). There were no serious complications. CONCLUSION: US
      guided PEA appears to be a safe and effective minimally invasive technique for
      management of primary non-parasitic splenic cysts.

PMID- 27039326
TI  - Quantitative assessment of angiographic perfusion reduction using color-coded
      digital subtraction angiography during transarterial chemoembolization.
AB  - PURPOSE: The aim of this study was to develop a quantitative measurement of
      perfusion reduction using color-coded digital subtraction angiography (ccDSA) to
      monitor intra-procedural arterial stasis during TACE. MATERIALS AND METHODS: A
      total number of 35 patients with hepatocellular carcinoma who had undergone TACE
      were enrolled into the study. Pre- and post-two-dimensional digital subtraction
      angiography scans were conducted with same protocol and post-processed with ccDSA
      prototype software. Time-contrast-intensity (CI[t]) curve was obtained by region
      of-interest (ROI) measurement on the generated ccDSA image. Quantitative 2D
      perfusion parameters time to peak, area under the curve (AUC), maximum upslope,
      and contrast intensity peak (CI-Peak) derived from the ROI-based CI[t] curve for
      pre- and post-TACE were evaluated to assess the reduction of antegrade blood flow
      and tumor blush. Relationships between 2D perfusion parameters, subjective
      angiographic chemoembolization endpoint (SACE) scale, and clinical outcomes were
      analyzed. RESULTS: Area normalized AUC and CI-Peak revealed significant reduction
      after the TACE (P < 0.0001). AUCnorm decreased from pre-procedure of 0.867 +/-
      0.242 to 0.421 +/- 0.171 (P < 0.001) after completion of TACE. CI-Peaknorm was
      0.739 +/- 0.221 before TACE and 0.421 +/- 0.174 (P < 0.001) after TACE. Tumor
      blood supply time slowed down obviously after embolization. A perfusion reduction
      either from AUCnorm or CI-Peaknorm ranging from 30% to 40% was associated with
      SACE level III and a reduction ranging from 60% to 70% was equivalent to SACE
      level IV. For intermediate reduction (SACE level III), better tumor response was
      found after TACE rather than a higher reduction (SACE level IV). CONCLUSION:
      ccDSA application provides an objective approach to quantify the perfusion
      reduction and subjectively evaluate the arterial stasis of antegrade blood flow
      and tumor blush caused by TACE.

PMID- 27039327
TI  - Beyond appendicitis; radiologic review of unusual and rare pathology of the
      appendix.
AB  - Appendicitis is a very common cause of acute abdominal pathology, however, many
      other pathologic conditions of the appendix can be diagnosed utilizing CT.
      Examples of these conditions include primary appendiceal neoplasms, secondary
      inflammation of the appendix, stump appendicitis, endometriosis, appendicitis
      within a hernia, appendiceal diverticulosis and intussusception and intraluminal
      foreign bodies. The purpose of this article is to review appendiceal pathology
      outside of acute appendicitis, describe corresponding imaging findings on CT, and
      to illustrate various CT findings of appendiceal disease with representative
      cases. 

PMID- 27039328
TI  - The "winking owl" sign.

PMID- 27039329
TI  - Surgical versus conservative interventions for treating anterior cruciate
      ligament injuries.
AB  - BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is a common injury,
      mainly affecting young, physically active individuals. The injury is
      characterised by joint instability, leading to decreased activity, which can lead
      to poor knee-related quality of life. It is also associated with increased risk
      of secondary osteoarthritis of the knee. It is unclear whether stabilising the
      knee surgically via ACL reconstruction produces a better overall outcome than non
      surgical (conservative) treatment. OBJECTIVES: To assess the effects of surgical
      versus conservative interventions for treating ACL injuries. SEARCH METHODS: We
      searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register
      (18 January 2016), the Cochrane Central Register of Controlled Trials (2016,
      Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In-Process & Other Non
      Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial
      registers (February 2016) and reference lists. SELECTION CRITERIA: We included
      randomised controlled trials that compared the use of surgical and conservative
      interventions in participants with an ACL rupture. We included any trial that
      evaluated surgery for ACL reconstruction using any method of reconstruction, type
      of reconstruction technique, graft fixation or type of graft. DATA COLLECTION AND
      ANALYSIS: Three review authors independently screened all titles and abstracts
      for potentially eligible studies, for which we then obtained full-text reports.
      Two authors then independently confirmed eligibility, extracted data and assessed
      the risk of bias using the Cochrane 'Risk of bias' tool. We used the GRADE
      approach to assess the overall quality of the evidence. MAIN RESULTS: We
      identified one study in which 141 young, active adults with acute ACL injury were
      randomised to either ACL reconstruction followed by structured rehabilitation
      (results reported for 62 participants) or conservative treatment comprising
      structured rehabilitation alone (results reported for 59 participants). Built
      into the study design was a formal option for subsequent (delayed) ACL
      reconstruction in the conservative treatment group, if the participant requested
      surgery and met pre-specified criteria.This study was deemed at low risk of
      selection and reporting biases, at high risk of performance and detection biases
      because of the lack of blinding and at unclear risk of attrition bias because of
      an imbalance in the post-randomisation exclusions. According to GRADE
      methodology, the overall quality of the evidence was low across different
      outcomes.This study identified no difference in subjective knee score (measured
      using the average score on four of the five sub-scales of the KOOS score (range
      from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and
      conservative treatment at two years (difference in KOOS-4 change from baseline
      scores: MD -0.20, 95% confidence interval (CI) -6.78 to 6.38; N = 121
      participants; low-quality evidence), or at five years (difference in KOOS-4 final
      scores: MD -2.0, 95% CI -8.27 to 4.27; N = 120 participants; low-quality
      evidence). The total number of participants incurring one or more complications
      in each group was not reported; serious events reported in the surgery group were
      predominantly surgery-related, while those in conservative treatment group were
      predominantly knee instability. There were also incomplete data for total
      participants with treatment failure, including subsequent surgery. In the
      surgical group at two years, there was low-quality evidence of far fewer ACL
      related treatment failures, when defined as either graft rupture or subsequent
      ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the
      participants in the conservative treatment group of ACL reconstruction for knee
      instability at two years and by 51% (30/59) of the participants at five years.
      There was low-quality evidence of little difference between the two groups in
      participants who had undergone meniscal surgery at anytime up to five years.
      There was low-quality evidence of no clinically important between-group
      differences in SF-36 physical component scores at two years. There was low
      quality evidence of a higher return to the same or greater level of sport
      activity at two years in the ACL reconstruction group, but the wide 95% CI also
      included the potential for a higher return in the conservative treatment group.
      Based on an illustrative return to sport activities of 382 per 1000
      conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL
      reconstruction patients (95% CI 84 fewer to 348 more). There was very low-quality
      evidence of a higher incidence of radiographically-detected osteoarthritis in the
      surgery group (19/58 (35%) versus 10/55 (18%)). AUTHORS' CONCLUSIONS: For adults
      with acute ACL injuries, we found low-quality evidence that there was no
      difference between surgical management (ACL reconstruction followed by structured
      rehabilitation) and conservative treatment (structured rehabilitation only) in
      patient-reported outcomes of knee function at two and five years after injury.
      However, these findings need to be viewed in the context that many participants
      with an ACL rupture remained symptomatic following rehabilitation and later opted
      for ACL reconstruction surgery. Further research, including the two identified
      ongoing trials, will help to address the limitations in the current evidence,
      which is from one small trial in a young, active, adult population.

PMID- 27039330
TI  - Myoclonus: Pathophysiology and Treatment Options.
AB  - OPINION STATEMENT: Treatment of myoclonus requires an understanding of the
      physiopathology of the condition. The first step in treatment is to determine if
      there is an epileptic component to the myoclonus and treat accordingly. Secondly,
      a review of medications (e.g., opiates) and comorbidities (e.g., hepatic or renal
      failure) is required to establish the possibility of iatrogenic and reversible
      conditions. Once those are eliminated, delineation between cortical, cortico
      subcortical, subcortical, brainstem, and spinal generators can determine the
      first-line treatment. Cortical myoclonus can be treated with levetiracetam,
      valproic acid, and clonazepam as first-line agents. Phenytoin and carbamazepine
      may paradoxically worsen myoclonus. Subcortical and brainstem myoclonus can be
      treated with clonazepam as a first-line agent, but levetiracetam and valproic
      acid can be tried as well. L-5-Hydroxytryptophan and sodium oxybate are agents
      used for refractory cases. Spinal myoclonus does not respond to anti-epileptic
      drugs, and clonazepam is a first-line agent. Botulinum toxin treatment can be
      useful for focal cases of spinal myoclonus. The etiology of propriospinal
      myoclonus is controversial, and a functional etiology is suspected in most cases.
      Treatment can include clonazepam, levetiracetam, baclofen, valproate,
      carbamazepine, and zonisamide. Functional myoclonus requires multimodal and
      multidisciplinary treatment that may include psychotropic drugs and physical and
      occupational therapy. Close collaboration between neurologists and psychiatrists
      is required for effective treatment. Finally, deep brain stimulation targeting
      the globus pallidus pars-interna bilaterally has been used in myoclonus-dystonia
      when pharmacological treatments have been exhausted.

PMID- 27039331
TI  - Comprehensive techno-economic analysis of wastewater-based algal biofuel
      production: A case study.
AB  - Combining algae cultivation and wastewater treatment for biofuel production is
      considered the feasible way for resource utilization. An updated comprehensive
      techno-economic analysis method that integrates resources availability into
      techno-economic analysis was employed to evaluate the wastewater-based algal
      biofuel production with the consideration of wastewater treatment improvement,
      greenhouse gases emissions, biofuel production costs, and coproduct utilization.
      An innovative approach consisting of microalgae cultivation on centrate
      wastewater, microalgae harvest through flocculation, solar drying of biomass,
      pyrolysis of biomass to bio-oil, and utilization of co-products, was analyzed and
      shown to yield profound positive results in comparison with others. The estimated
      break even selling price of biofuel ($2.23/gallon) is very close to the
      acceptable level. The approach would have better overall benefits and the
      internal rate of return would increase up to 18.7% if three critical components,
      namely cultivation, harvest, and downstream conversion could achieve
      breakthroughs. 

PMID- 27039334
TI  - [Flagellate erythema].

PMID- 27039333
TI  - [Alcohol-related neuropsychological impairments: Nature, impact and detection].
AB  - Alcohol-related neuropsychological deficits result from chronic and excessive
      alcohol consumption and are associated with structural and functional damage of
      Papez's circuit and frontocerebellar circuit. Alcohol-related cognitive deficits
      are heterogeneous but especially affect executive functions and memory abilities.
      They result in difficulties to change alcohol behavior combined with a tendency
      for patients to overestimate their capacity to succeed. Alcohol-related cognitive
      deficits could be a risk-factor for relapse since they hamper patients to benefit
      fully from treatment (especially when based on relapse prevention). Screening
      tools usable by non-psychologists are available and can be completed by an
      extensive neuropsychological examination conducted by a neuropsychologist when
      necessary. Alcohol treatment should be adjusted to take alcohol-related cognitive
      deficits into account, by promoting longer treatment in healthy environment for
      example. Improvements of alcohol treatment options, including specific
      neuropsychological rehabilitation, are required for patients with persistent
      alcohol-related cognitive deficits.

PMID- 27039332
TI  - Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus
      Macaques.
AB  - The abuse of opiates such as morphine in synergy with HIV infection not only
      exacerbates neuropathogenesis but significantly impacts behavioral attributes in
      HIV infected subjects. Thus, the goal of the current study was to characterize
      behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV
      infection. Specifically, we assessed three behavioral tasks: motor skill (MS),
      forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline
      control data (44 weeks) and data during the morphine-only dependency period (26
      weeks), a subset of animals were productively infected with neurovirulent strains
      of SIVmac (R71/E17) for an additional 33 weeks. A general pattern in the results
      is that behavioral decline occurred with high CSF viral loads but not necessarily
      with high plasma viral loads. Compared to saline controls, all treated animals
      showed significant decreases in performance on all three behavioral tasks during
      the morphine-only dependency period. During the post infection period, only the
      morphine plus SIV group showed a significant further decline and this only
      occurred for the MS task. Taken together, these data demonstrate a clear effect
      of morphine to produce behavioral deficits and also suggest that morphine can act
      synergistically with SIV/HIV to exacerbate behavioral deficits.

PMID- 27039335
TI  - [Seasonality in asthma: Impact and treatments].
AB  - The role of seasons should be taken into account in the management of asthma. The
      environment varies between seasons and it is well documented that asthma is
      modulated by environment. Viruses cause asthma exacerbations peak, in winter, in
      adults while the peak is present in September in children. Allergens are probably
      a less powerful source of asthma exacerbation than viruses but pollen involvement
      in spring and summer and dust mites in autumn are indisputable. Air pollutants,
      present in summer during the hottest periods, are also highly involved in asthma
      exacerbations. Indoor air pollution, in winter, is also implicated in asthma
      disease. All these environmental factors are synergistic and increase the risk of
      asthma exacerbation. Therapies should be adapted to each season depending on
      environmental factors potentially involved in the asthma disease.

PMID- 27039336
TI  - [Hallucinations and Parkinson's disease in the elderly: Pitfalls and medical
      care].
AB  - Hallucinations are common neuropsychiatric symptoms in Parkinson's disease (PD),
      with a significant prognosis impact. It is necessary to rule out other diagnoses
      that can be mentioned when hallucinations occur in old patients with PD. The
      various etiological factors must be systematically checked and can help for
      diagnosis. Medical care will be focused on treating the primary cause (medical or
      iatrogenic origin) and will privilege non-pharmacological strategies. Due to
      their frequent adverse effects, antipsychotic medication should be limited and
      started at low dose in old patients with multiple comorbidities. Clozapine and
      quetiapine have the highest level of recommendation in this indication. In the
      future, defining fMRI-based targets for noninvasive brain stimulation tools
      should pave the way for innovative non-pharmacological treatment of
      hallucinations. 

PMID- 27039337
TI  - Structural requirements of acylated Gly-l-Ala-d-Glu analogs for activation of the
      innate immune receptor NOD2.
AB  - The fragment of bacterial peptidoglycan muramyl dipeptide (MDP) has long been
      known for its adjuvant activity, however the underlying mechanism of this action
      has only recently been elucidated. It is ascribed to its agonist action on the
      nucleotide-binding oligomerization domain-containing protein 2 (NOD2). In spite
      of the pressing need for novel adjuvants for human use, this discovery is
      hampered, by not knowing the structural requirements underlying the
      immunostimulatory activity. We have investigated how minor modifications of hit
      compound acyl Gly-L-Ala-D-Glu derivative I modulate the molecular recognition by
      NOD2. A series of novel desmuramyldipeptides has been designed and synthesized
      leading to the identification of compound 16, in which the sugar moiety is
      replaced by a 6-phenylindole moiety, that exhibits the strongest NOD2 activation
      to date sans the carbohydrate moiety. The results have enabled a deeper
      understanding of the structural requirements of desmuramylpeptides for NOD2
      activation. 

PMID- 27039338
TI  - Medicinal leech therapy and Aeromonas spp. infection.
AB  - While the use of medicinal leech therapy (MLT) in reconstructive and orthopaedic
      surgery is widely described, post-operative complications related to leeches
      remain a major concern. Aeromonas spp. strains are involved in the majority of
      reported cases. As surgical success rate is directly impacted, an adapted
      antibiotic prophylaxis should be instituted in order to minimize these
      complications. We assessed pharmaceutical process, microbiological control and
      related infections in order to provide data and choose the appropriate
      antibiotherapy for patients requiring MLT. We report a clinical and
      microbiological study over a 24-month period. Clinical data were collected from
      patients' database, and microbiological analysis both on leeches' tank water and
      crushed leeches were performed to characterize isolated strains and their
      susceptibility to antibiotics. A total of 595 leeches were used to treat 28
      patients (12 in plastic surgery and 16 in orthopaedic surgery), and three
      documented cases of post-operative infections were reported. Aeromonas spp.
      isolates yielded from 62 % of analyzed batches (75 % of Aeromonas veronii).
      Eighteen Aeromonas spp. isolates yielded from 23 water samples and three crushed
      leeches. Isolates were similar in tank and crushed leeches. Strains were
      susceptible to fluoroquinolones, sulfamethoxazole/trimethoprim, aminosides, and
      third-generation cephalosporins but resistant to amoxicillin/clavulanic acid and
      second-generation cephalosporins. According to collected data, routine tank water
      microbiological analyses are mandatory in order to identify leeches' batches
      containing resistant strains and to discard them. In this context, the surgeon is
      able to select an appropriated antibiotic prophylaxis in order to avoid MLT
      associated serious post-operative complications. 

PMID- 27039339
TI  - Early detection of Mycobacterium tuberculosis complex in BACTEC MGIT cultures
      using nucleic acid amplification.
AB  - We evaluated the application of nucleic acid amplification (NAA) in liquid
      cultures for the early detection of Mycobacterium tuberculosis. The Cobas TaqMan
      MTB test, IS6110 real-time PCR, and hsp65 PCR-restriction fragment length
      polymorphism (RFLP) analysis were used to detect BACTEC MGIT 960 (MGIT) cultures
      on days 3, 5, 7, and 14. The procedure was initially tested with a reference
      strain, H37Rv (ATCC 27294). Subsequently, 200 clinical specimens, including 150
      Acid Fast bacillus (AFB) smear-positive and 50 AFB smear-negative samples, were
      examined. The Cobas TaqMan MTB test and IS6110-based PCR analysis were able to
      detect M. tuberculosis after 1 day when the inoculum of H37Rv was >3 x 10(-2)
      CFU/ml. After a 5-day incubation in the MGIT system, all three NAA assays had a
      positive detection regardless of the inoculum size. After a 1-day incubation of
      the clinical specimens in the MGIT system, the sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) for the Cobas TaqMan
      MTB assay were 70.2%, 100%, 100%, and 82.3% respectively. For IS6110-based PCR
      analysis, these values were 63.1%, 100%, 100%, and 78.9%, and were 88.1%, 100%,
      100%, and 92.1% respectively for hsp65 PCR-RFLP analysis. After a 3-day
      incubation, the specificity and PPV were 100% for all three NAA tests; the Cobas
      TaqMan MTB assay had the best sensitivity (97.6%) and NPV (98.3%). The
      sensitivity, specificity, PPV, and NPV for conventional culture analysis were
      98.8%, 100%, 100%, and 99.1%. Thus, NAA may be useful for the early detection of
      M. tuberculosis after 3 days in MGIT. 

PMID- 27039340
TI  - Serum concentrations of amoxicillin in neonates during continuous intravenous
      infusion.
AB  - Amoxicillin is commonly used for the treatment of neonatal bacterial infection
      with intermittent dosing (ID) regimens. However, increasing bacterial resistance,
      in addition to a lack of new antimicrobial agents, urges the optimization of
      current therapeutic options. Clinical studies in adults suggest continuous
      infusion (CI) regimens of beta-lactam antibiotics to be superior to ID. There are
      as yet no guidelines concerning the CI dosing of amoxicillin. The present study
      was developed to describe the CI pharmacokinetics and -dynamics of amoxicillin
      during the first 3 days of life in search of the optimal dosing regimen. Neonates
      with a gestational age above 34 weeks, at risk of neonatal infection and
      requiring amoxicillin therapy, were included. Serum concentrations of amoxicillin
      were measured during CI on days 1 and 3 in the steady state. Twenty-two serum
      samples of 11 patients were collected. All patients reached and retained serum
      concentrations of amoxicillin within the therapeutic range without exceeding the
      toxic concentration (serum concentrations on day 1 mean 55.4 mg/l, range 30.9
      69.5, SD 10.5, and on day 3 48.8 mg/l, range 25.5-92.4, SD 18.4). There was no
      significant decrease in concentration from day 1 to day 3 (p = 0.38). This study
      showed therapeutic, nontoxic concentrations of amoxicillin in neonates on CI of
      amoxicillin in the first 3 days of life. Randomized controlled trials should
      reveal whether the clinical benefits of the CI of amoxicillin exceed those of ID
      regimens. 

PMID- 27039341
TI  - Impact of systemic antifungal therapy on the detection of Candida species in
      blood cultures in clinical cases of candidemia.
AB  - The diagnosis and follow-up of candidemia still rely on blood cultures (BCs). In
      vitro studies show that antifungals can significantly modify the result of blood
      culture not containing adsorbing agents. We aimed to evaluate, under clinical
      conditions, the impact on BC yeast detection of systemic antifungal therapy
      (SAT). Patients (n = 125) experiencing candidemia at Grenoble University Hospital
      (France) were included in a 4-year retrospective study. The Plus Aerobic/F
      (Aerobic) and Plus Anaerobic/F (Anaerobic) bottles, which both contain adsorbing
      resins and the non-resin selective Mycosis IC/F (Mycosis) bottles, were compared
      using multivariate hierarchical models adjusted for clinical characteristics. The
      positivity rate (PR) is decreased in patients with SAT (p < 0.01), abdominal
      surgery (p = 0.01), and hemodialysis (p = 0.02). In all bottles, SAT reduces PR
      by a factor of 0.16 (95 % CI: [0.08; 0.32]) and increases the time to positivity
      (TTP) by a factor of 1.76 ([1.30; 2.40]; p < 0.01). In the presence of SAT, TTP
      is higher in non-resin bottles (Mycosis) than in resin bottles (RR = 1.76, [1.30;
      2.40]); however, the TTP in nonresin and resin bottles remains comparable.
      Although discordant results are observed with and without SAT (37 and 58 %
      respectively), we showed that the presence of SAT decreases significantly the
      agreement rate by a factor of 0.29 (CI: [0.12; 0.68]). The combination of
      Anaerobic and Mycosis bottles allowed a 100 % positivity rate for C. glabrata.
      SAT significantly affects BC results. Because they provide additional and
      complementary results, this study supports the concomitant use of resin and
      selective bottles, especially in patients receiving SAT. 

PMID- 27039342
TI  - Paediatric nasopharyngeal cytology: a new diagnostic opportunity?
AB  - The purpose of this investigation was to describe the first application of
      nasopharyngeal cytology (NPC), a new cytological technique to collect cellular
      material from the nasopharyngeal surface non-invasively in children with chronic
      adenoiditis associated with recurrent acute otitis media and/or otitis media with
      effusion. Cellular material was collected transorally using an extra-thin
      flexible wire nasopharyngeal swab and then examined under a light microscope. The
      diagnostic accuracy of NPC in detecting the presence of allergy and pathogens
      (compared to microbiological evaluation of nasopharyngeal aspirates, NPAs) was
      assessed. NPC was performed on 121 children (mean age 69.4 +/- 15.5 months).
      Inflammatory cells and pathogens were detected in 61.1 % and 44.2 % of patients,
      respectively. The specificity of nasopharyngeal eosinophils in detecting allergy
      was good (91.9 %), as was the specificity of mast cells, but the sensitivities
      were less. The NPAs revealed bacterial colonisation in 84.7 % of the patients,
      and Streptococcus pneumoniae was the most frequently isolated (60.0 %). NPC
      revealed the presence of bacteria in 94.9 % of patients, including bacillary
      species in 33.9 %. NPC was highly sensitive in detecting pathogens (96.0 %). Its
      specificity in detecting bacillary species was fairly good (75.0 %), but the
      corresponding values of the specificity of NPC in detecting pathogens and its
      sensitivity in detecting bacillary species were poor. Our findings suggest the
      need for more structured studies that can test the real effectiveness and
      usefulness of NPC in defining nasopharyngeal cytological patterns in children
      with chronic nasopharyngeal diseases by comparing it with established diagnostic
      techniques. 

PMID- 27039343
TI  - Innate immune evasion of Escherichia coli clinical strains from orthopedic
      implant infections.
AB  - Escherichia coli is one of the first causes of Gram-negative orthopedic implant
      infections (OII). Those infections, usually hematogenous, mostly originate from
      the urinary tract. We investigated the strategies developed by E. coli in this
      context to evade host innate immune responses, i.e. complement and
      polymorphonuclear neutrophils (PMN). Twenty strains from OII were compared with
      20 strains from bacteremia in patients with non-infected orthopedic implant. In
      both groups, 6/20 (30 %) strains lysed PMNs, due to the production of the pore
      forming toxin alpha-hemolysin (HlyA). For the others, resistance to phagocytic
      killing by PMN was not significantly different between both groups. In contrast,
      resistance to complement-mediated serum killing was significantly higher in OII
      strains than in the others (65 % vs 10 %; P <0.001). In E. coli, different
      mechanisms have been involved in complement resistance. Here, serum resistance
      was not linked to a group 2 capsule, or a loss of outer membrane permeability, or
      the recruitment of the complement inhibitor C4bp, but was significantly
      associated with the synthesis of long-chain LPS, regardless of the O-antigen.
      Thus, serum resistance could promote seeding of peri-implant tissues by helping
      E. coli to either persist in blood and reach the site of infection or overcome
      localized complement activation. 

PMID- 27039346
TI  - Global form and motion processing in healthy ageing.
AB  - The ability to perceive biological motion has been shown to deteriorate with age,
      and it is assumed that older adults rely more on the global form than local
      motion information when processing point-light walkers. Further, it has been
      suggested that biological motion processing in ageing is related to a form-based
      global processing bias. Here, we investigated the relationship between older
      adults' preference for form information when processing point-light actions and
      an age-related form-based global processing bias. In a first task, we asked older
      (>60years) and younger adults (19-23years) to sequentially match three different
      point-light actions; normal actions that contained local motion and global form
      information, scrambled actions that contained primarily local motion information,
      and random-position actions that contained primarily global form information.
      Both age groups overall performed above chance in all three conditions, and were
      more accurate for actions that contained global form information. For random
      position actions, older adults were less accurate than younger adults but there
      was no age-difference for normal or scrambled actions. These results indicate
      that both age groups rely more on global form than local motion to match point
      light actions, but can use local motion on its own to match point-light actions.
      In a second task, we investigated form-based global processing biases using the
      Navon task. In general, participants were better at discriminating the local
      letters but faster at discriminating global letters. Correlations showed that
      there was no significant linear relationship between performance in the Navon
      task and biological motion processing, which suggests that processing biases in
      form- and motion-based tasks are unrelated. 

PMID- 27039344
TI  - Structural and functional neural adaptations in obstructive sleep apnea: An
      activation likelihood estimation meta-analysis.
AB  - Obstructive sleep apnea (OSA) is a common multisystem chronic disorder.
      Functional and structural neuroimaging has been widely applied in patients with
      OSA, but these studies have often yielded diverse results. The present
      quantitative meta-analysis aims to identify consistent patterns of abnormal
      activation and grey matter loss in OSA across studies. We used PubMed to retrieve
      task/resting-state functional magnetic resonance imaging and voxel-based
      morphometry studies. Stereotactic data were extracted from fifteen studies, and
      subsequently tested for convergence using activation likelihood estimation. We
      found convergent evidence for structural atrophy and functional disturbances in
      the right basolateral amygdala/hippocampus and the right central insula.
      Functional characterization of these regions using the BrainMap database
      suggested associated dysfunction of emotional, sensory, and limbic processes.
      Assessment of task-based co-activation patterns furthermore indicated that the
      two regions obtained from the meta-analysis are part of a joint network
      comprising the anterior insula, posterior-medial frontal cortex and thalamus.
      Taken together, our findings highlight the role of right amygdala, hippocampus
      and insula in the abnormal emotional and sensory processing in OSA.

PMID- 27039347
TI  - Differential expression of microRNAs in plasma of patients with prediabetes and
      newly diagnosed type 2 diabetes.
AB  - AIMS: MicroRNAs (miRNAs) are present in plasma and have emerged as critical
      regulators of gene expression at posttranscriptional level, and thus are involved
      in various human diseases, including diabetes. The objective of this study was to
      screen and validate differentially expressed plasma miRNAs in prediabetes and
      newly diagnosed type 2 diabetes (T2D). METHODS: In this study, we screened
      differentially expressed plasma miRNAs in prediabetes and newly diagnosed T2D by
      miRNA microarray analysis, and validated the expression of candidate miRNAs using
      quantitative reverse transcription polymerase chain reaction assays. Furthermore,
      we performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes
      (KEGG) pathway analyses to disclose functional enrichment of genes predicted to
      be regulated by the differentially expressed miRNAs. RESULTS: Notably, our
      results revealed that hsa-miR-1249, hsa-miR-320b, and hsa-miR-572 (P < 0.05) were
      differentially expressed among the three groups, which yielded an area under the
      receiver operator characteristics curve (AUC) of 0.784 [95 % confidence interval
      (CI) 0.685-0.883], 0.946 (95 % CI 0.906-0.985), and 0.843 (95 % CI 0.766-0.920)
      discriminating T2D patients from NGT control groups, respectively, while the AUC
      was 0.887 (95 % CI 0.818-0.957), 0.635 (95 % CI 0.525-0.744), and 0.69 (95 % CI
      0.580-0.793) discriminating prediabetes patients from NGT control groups,
      respectively. In addition, GO and KEGG pathway analyses showed that genes
      predicted to be regulated by differentially expressed miRNAs were significantly
      enriched in several related biological processes and pathways, including the
      development of multicellular organisms, signal transduction, cell
      differentiation, apoptosis, cell metabolism, ion transport regulation, and other
      biological functions. CONCLUSIONS: Taken together, our results showed
      differentially expressed miRNAs in T2D and prediabetes. Plasma hsa-miR-1249, hsa
      miR-320b, and hsa-miR-572 may serve as novel biomarkers for diagnosis and
      potential targets for the treatment for prediabetes and T2D.

PMID- 27039348
TI  - A Modification to Simplify the Harvest of a Hemi-hamate Autograft.
AB  - Hemi-hamate arthroplasty is a valuable option for subacute dorsal fracture
      dislocations of the proximal interphalangeal joint. Various harvesting techniques
      have been recommended via both anterograde and retrograde directions, both posing
      some technical challenges. We propose a technique for simplifying the hemi-hamate
      graft harvest by creating a window of visualization onto the dorsal hamate
      articular surface. This is achieved by resection of the dorsal-ulnar base of
      fourth metacarpal and the dorsal-radial base of the fifth metacarpal. This makes
      it easier to measure and cut the hamate articular surface. It also provides a
      properly shaped graft that can be inset in the middle phalangeal defect without
      using backgrafting, and allowing screws to be placed perpendicular to the graft
      defect to obtain direct compression. 

PMID- 27039345
TI  - Why estrogens matter for behavior and brain health.
AB  - The National Institutes of Health (NIH) has required the inclusion of women in
      clinical studies since 1993, which has enhanced our understanding of how
      biological sex affects certain medical conditions and allowed the development of
      sex-specific treatment protocols. However, NIH's policy did not previously apply
      to basic research, and the NIH recently introduced a new policy requiring all new
      grant applications to explicitly address sex as a biological variable. The policy
      itself is grounded in the results of numerous investigations in animals and
      humans illustrating the existence of sex differences in the brain and behavior,
      and the importance of sex hormones, particularly estrogens, in regulating
      physiology and behavior. Here, we review findings from our laboratories, and
      others, demonstrating how estrogens influence brain and behavior in adult
      females. Research from subjects throughout the adult lifespan on topics ranging
      from social behavior, learning and memory, to disease risk will be discussed to
      frame an understanding of why estrogens matter to behavioral neuroscience.

PMID- 27039349
TI  - The Outcomes of Arthroscopic Repair Versus Debridement for Chronic Unstable
      Triangular Fibrocartilage Complex Tears in Patients Undergoing Ulnar-Shortening
      Osteotomy.
AB  - PURPOSE: The aim of this study was to compare the results of arthroscopic
      peripheral repair (AR) and arthroscopic debridement (AD) for the treatment of
      chronic unstable triangular fibrocartilage complex (TFCC) tears in ulnar-positive
      patients undergoing ulnar-shortening osteotomy (USO). METHODS: A total of 31
      patients who underwent arthroscopic treatments combined with USO for unstable
      TFCC tears and were followed-up at a minimum of 24 months were included in this
      retrospective cohort study. Fifteen patients were treated with AR, and 16
      patients were treated with AD while at the same time undergoing a USO. Outcome
      measures included wrist range of motion, grip strength, Disabilities of the Arm,
      Shoulder, and Hand (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, and
      overall outcomes according to the modified Mayo wrist scoring system. In
      addition, a stress test to assess distal radioulnar joint (DRUJ) stability was
      performed before and after surgery to compare the 2 cohorts. RESULTS: Both
      respective cohorts showed significant improvements in grip strength and
      subjective scores at the final follow-up. Grip strength, DASH, and PRWE scores
      were better in the AR group than in the AD group. The recovery rate from DRUJ
      instability observed during the preoperative examination was superior in the AR
      group. CONCLUSIONS: Both AD and AR of the TFCC combined with USO are reliable
      procedures with satisfactory clinical outcomes for unstable TFCC tears in ulnar
      positive patients. However, AR of the TFCC is suggested if DRUJ stability is
      concomitantly compromised. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 27039350
TI  - Strategy and design of Innovation Policy Road Mapping for a waste biorefinery.
AB  - Looming energy crisis, climate change concerns coupled with decreasing fossil
      fuel resources has garnered significant global attention toward development of
      alternative, renewable, carbon-neutral and eco-friendly fuels to fulfil
      burgeoning energy demands. Waste utilization and its management are being pursued
      with renewed interest due to the gamut of biobased products it can offer apart
      from providing enough energy to meet a major fraction of the world's energy
      demand. Biorefining is the sustainable processing of biomass into a spectrum of
      marketable products and energy. Integrating all components of waste treatment
      culminating into biobased products and energy recovery in a single integrated
      waste biorefinery is self sufficient, highly sustainable and is very beneficial.
      Designing systematic innovation policies are essential for development and
      commercialization of new technologies in this important futuristic research area.
      This communication explores Innovation Policy Road Mapping (IPRM) methodology
      available in the literature and applies it to design integrated waste
      biorefinery. 

PMID- 27039351
TI  - Effect of Chinese medicinal herbal residues on microbial community succession and
      anti-pathogenic properties during co-composting with food waste.
AB  - This study investigated the antimicrobial properties of Chinese medicinal herbal
      residues (CMHRs) during its co-composting with food waste (FW) in two different
      ratios along with a control. Inhibition on total microbial population were
      assessed while the numerically dominant microbes were isolated and their
      antagonistic effects were assessed. Results indicate that the active ingredients
      persist in the composting mass did not affect the microbes unspecifically as
      revealed from almost similar bacterial and fungal populations. Rather specific
      inhibitory activities against Alternaria solani and Fusarium oxysporum were
      observed. Apart from the CMHR-born active compounds, CMHR-induced changes in the
      antagonistic and mycoparasitic abilities of the bacteria and fungi also
      contribute to the specific inhibition against the tested pathogens. Therefore use
      of CMHRs during the composting of CMHRs enhances its antipathogenic property
      resulting in an anti-pathogenic compost. 

PMID- 27039352
TI  - Innovative method for increased methane recovery from two-phase anaerobic
      digestion of food waste through reutilization of acidogenic off-gas in
      methanogenic reactor.
AB  - In this study, the performance of a two-phase anaerobic digestion reactor
      treating food waste with the reutilization of acidogenic off-gas was investigated
      with the objective to improve the hydrogen availability for the methanogenic
      reactor. As a comparison a treatment without off-gas reutilization was also set
      up. Results showed that acidogenic off-gas utilization in the upflow anaerobic
      sludge blanket (UASB) reactor increased the methane recovery up to 38.6%. In
      addition, a 27% increase in the production of cumulative chemical oxygen demand
      (COD) together with an improved soluble microbial products recovery dominated by
      butyrate was observed in the acidogenic leach bed reactor (LBR) with off-gas
      reutilization. Of the increased methane recovery, ~8% was contributed by the
      utilization of acidogenic off-gas in UASB. Results indicated that utilization of
      acidogenic off-gas in methanogenic reactor is a viable technique for improving
      overall methane recovery. 

PMID- 27039353
TI  - Performance of organics and nitrogen removal in subsurface wastewater
      infiltration systems by intermittent aeration and shunt distributing wastewater.
AB  - Organics and nitrogen removal in four subsurface wastewater infiltration systems
      (SWISs), named SWIS A (without intermittent aeration and shunt distributing
      wastewater), SWIS B (with intermittent aeration), SWIS C (with shunt distributing
      wastewater) and SWIS D (with intermittent aeration and shunt distributing
      wastewater) was investigated. High average removal rates of 92.3% for COD, 90.2%
      for NH4-N and 88.1% for TN were achieved simultaneously in SWIS D compared with
      SWIS A, B and C. The excellent TN removal of SWIS D was due to intermittent
      aeration provided sufficient oxygen for nitrification in upper matrix and the
      favorable anoxic or anaerobic environment for denitrification in subsequent
      matrix, and moreover, shunt distributing wastewater provided sufficient carbon
      source for denitrification process. The results indicated that intermittent
      artificial aeration combined with shunt distributing wastewater could achieve
      high organics and nitrogen removal in SWISs. 

PMID- 27039354
TI  - Recent advances in yeast cell-surface display technologies for waste
      biorefineries.
AB  - Waste biorefinery aims to maximize the output of value-added products from
      various artificial/agricultural wastes by using integrated bioprocesses. To make
      waste biorefinery economically feasible, it is thus necessary to develop a low
      cost, environment-friendly technique to perform simultaneous biodegradation and
      bioconversion of waste materials. Cell-surface display engineering is a novel,
      cost-effective technique that can auto-immobilize proteins on the cell exterior
      of microorganisms, and has been applied for use with waste biofinery. Through
      tethering different enzymes (e.g., cellulase, lipase, and protease) or metal
      binding peptides on cell surfaces, various yeast strains can effectively produce
      biofuels and biochemicals from sugar/protein-rich waste materials, catalyze waste
      oils into biodiesels, or retrieve heavy metals from wastewater. This review
      critically summarizes recent applications of yeast cell-surface display on
      various types of waste biorefineries, highlighting its potential and future
      challenges with regard to commercializing this technology. 

PMID- 27039355
TI  - Synthesis and Cell Imaging of a Near-Infrared Fluorescent Magnetic "CdHgTe
      Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Composite.
AB  - In this article, a water-soluble near-infrared quantum dots of CdHgTe were
      prepared and subsequently combined with the drug delivery system "dextran
      magnetic layered double hydroxide-fluorouracil" (DMF) to build a new
      nanostructure platform in form of CdHgTe@DMF, in which the fluorescent probe
      function of quantum dots and the magnetic targeting transport and slow-release
      curative effect of DMF were blended availably together. The luminescent property
      particle size, and internal structure of the composite were characterized using
      fluorescence spectrophotometer, ultraviolet spectrophotometer, laser particle
      size distribution, TEM, X-ray diffraction, and Fourier transform infrared. The
      experimental study on fluorescent tags effect and magnetic targeting performance
      of the multifunctional platform were performed by fluorescent confocal imaging.
      The results showed that the CdHgTe could be grafted successfully onto the surface
      of DMF by electrostatic coupling. The CdHgTe@DMF composite showed super
      paramagnetic and photoluminescence property in the near-infrared wavelength range
      of 575-780 nm. Compared with CdHgTe, the CdHgTe@DMF composite could significantly
      improve the cell imaging effect, the label intensity increased with the magnetic
      field intensity, and obeyed the linear relationship Dmean = 1.758 + 0.0075M under
      the conditions of magnetic field interference. It can be implied that the
      CdHgTe@DMF may be an effective multifunction tool applying to optical bioimaging
      and magnetic targeted therapy.

PMID- 27039356
TI  - AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol-Poly(lactic-co
      glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non
      Small Cell Lung Cancer In Vitro.
AB  - Molecularly targeted drug delivery systems represent a novel therapeutic strategy
      in the treatment of different cancers. In the present study, we have developed
      gemcitabine (GEM)-loaded AS1411 aptamer surface-decorated polyethylene glycol
      poly(lactic-co-glycolic acid) nanopolymersome (Apt-GEM-NP) to target nucleolin
      overexpressing non-small cell lung cancer (NSCLC; A549). The prepared Apt-GEM-NP
      showed average particle size of 128 +/- 5.23 nm and spherical morphology with
      encapsulation efficiency and loading content of 95.32 +/- 2.37% and 8.61 +/-
      0.27%, respectively. Apt-GEM-NP exhibited a controlled release pattern. A
      sustained release of drug in physiological conditions will greatly improve the
      chemotherapeutic efficiency of a system. Enhanced cellular uptake and the
      cytotoxicity of aptamer-conjugated nanoparticles (NPs) in A549 cancer cells
      obviously verified nucleolin-mediated receptor-based active targeting. Nucleolin
      mediated internalization of the targeted polymeric NP was further confirmed by
      flow cytometry and fluorescence microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay clearly showed the enhanced cell proliferation
      inhibitory effect of AS1411-conjugated NP on account of the selective delivery of
      GEM to the nucleolin-overexpressing cancer cells. Our results showed that AS1411
      aptamer conjugation on the surface of NP could be a potential treatment strategy
      for A549 as a nucleolin-overexpressing cell line. This suggests that AS1411-GEM
      NPs could be potentially used for the treatment of NSCLC.

PMID- 27039357
TI  - Screening for diabetes in patients with cardiovascular disease: HbA1c trumps oral
      glucose tolerance testing.

PMID- 27039358
TI  - Peritonitis by Shewanella putrefaciens: Apropos of a case.

PMID- 27039359
TI  - New test for endothelin receptor type B (EDNRB) mutation genotyping in horses.
AB  - Lethal white foal syndrome (LWFS) is an autosomal recessive disease of neonatal
      foals characterized by a white hair coat and a functional intestinal obstruction.
      Traditional techniques for identifying the dinucleotide mutation (TC->AG) of the
      endothelin receptor B gene (EDNRB) associated with LWFS are time-consuming. We
      developed a new technique based on mutagenically separated polymerase chain
      reaction (MS-PCR) for simple detection of the EDNRB genotype in horses.

PMID- 27039360
TI  - Real-time monitoring of DNA methyltransferase activity using a hemimethylated
      smart probe.
AB  - A real-time assay for DNA methyltransferase (MTase) activity has been developed.
      A hemimethylated smart probe is used as the substrate for DNA MTase. Cleavage of
      the methylated product leads to separation of fluorophore from quencher, giving a
      proportional increase in fluorescence. The method permits real-time monitoring of
      DNA methylation process and makes it easy to characterize the activity of DNA
      MTase. It also has the potential to screen suitable inhibitor drugs for DNA
      MTase.

PMID- 27039362
TI  - Electrocoagulation using a rotated anode: A novel reactor design for textile
      wastewater treatment.
AB  - This paper investigates the optimum operational conditions of a novel rotated bed
      electrocoagulation (EC) reactor for the treatment of textile wastewater. The
      effect of various operational parameters such as rotational speed, current
      density (CD), operational time (RT), pH, temperature, and inter-electrode
      distance (IED) on the pollutant removal efficiency were examined. In addition,
      the consumption of aluminum (Al) and electrical energy, as well as operating
      costs at optimum conditions were also calculated. The results indicated that the
      optimum conditions for the treatment of textile wastewater were achieved at CD =
      4 mA/cm(2), RT = 10 min, rotational speed = 150 rpm, pH = 4.57, temperature = 25 
      degrees C, and IED = 1 cm. The electrode consumption, energy consumption, and
      operating costs were 0.038 kg/m(3), 4.66 kWh/m(3) and 0.44 US$/m(3),
      respectively. The removal efficiencies of chemical oxygen demand (COD),
      biological oxygen demand (BOD), total suspended solid (TSS), turbidity and color
      were 97.10%, 95.55%, 98%, 96% and 98.50%, respectively, at the first 10 min of
      reaction time, while the phenol compound of the wastewater was almost entirely
      removed (99.99%). The experimental results confirm that the new reactor design
      with rotated anode impellers and cathode rings provided high treatment efficiency
      at a reduced reaction time and with lower energy consumption. 

PMID- 27039361
TI  - Eriobotrya japonica seed biocomposite efficiency for copper adsorption:
      Isotherms, kinetics, thermodynamic and desorption studies.
AB  - Adsorption techniques are widely used to remove pollutants from wastewater;
      however, composites are gaining more importance due to their excellent adsorption
      properties. Bentonite composite with Eriobotrya japonica seed was prepared and
      used for the adsorption of copper (Cu) metal from aqueous media. The process
      variables such as pH, Cu(II) ions initial concentration, adsorbent dose, contact
      time and temperature were optimized for maximum Cu(II) adsorption. At pH 5,
      adsorbent dose 0.1 g, contact time 45 min, Cu(II) ions initial concentration 75
      mg/L and temperature 45  degrees C, maximum Cu(II) adsorption was achieved.
      Desorption studies revealed that biocomposite is recyclable. Langmuir, Freundlich
      and Harkins-Jura isotherms as well as pseudo-first and pseudo-second-order
      kinetics models were applied to understand the adsorption mechanism.
      Thermodynamic parameters (DeltaG(0), DeltaH(0) and DeltaS(0)) suggest that the
      adsorption process was spontaneous and endothermic in nature. The pseudo-second
      order kinetic model and Langmuir isotherm fitted well to the adsorption data.
      Results showed that biocomposite was more efficient for Cu(II) adsorption in
      comparison to individuals native Eriobotrya japonica seed biomass and Na
      bentonite. 

PMID- 27039363
TI  - Anodic oxidation of coke oven wastewater: Multiparameter optimization for
      simultaneous removal of cyanide, COD and phenol.
AB  - Anodic oxidation of industrial wastewater from a coke oven plant having cyanide
      including thiocyanate (280 mg L(-1)), chemical oxygen demand (COD - 1520 mg L(
      1)) and phenol (900 mg L(-1)) was carried out using a novel PbO2 anode. From
      univariate optimization study, low NaCl concentration, acidic pH, high current
      density and temperature were found beneficial for the oxidation. Multivariate
      optimization was performed with cyanide including thiocyanate, COD and phenol
      removal efficiencies as a function of changes in initial pH, NaCl concentration
      and current density using Box-Behnken experimental design. Optimization was
      performed for maximizing the removal efficiencies of these three parameters
      simultaneously. The optimum condition was obtained as initial pH 3.95, NaCl as 1
      g L(-1) and current density of 6.7 mA cm(-2), for which the predicted removal
      efficiencies were 99.6%, 86.7% and 99.7% for cyanide including thiocyanate, COD
      and phenol respectively. It was in agreement with the values obtained
      experimentally as 99.1%, 85.2% and 99.7% respectively for these parameters. The
      optimum conditions with initial pH constrained to a range of 6-8 was initial pH
      6, NaCl as 1.31 g L(-1) and current density as 6.7 mA cm(-2). The predicted
      removal efficiencies were 99%, 86.7% and 99.6% for the three parameters. The
      efficiencies obtained experimentally were in agreement at 99%, 87.8% and 99.6%
      respectively. The cost of operation for degradation at optimum conditions was
      calculated as 21.4 USD m(-3). 

PMID- 27039364
TI  - Role of nutrients and illuminance in predicting the fate of fungal mediated
      petroleum hydrocarbon degradation and biomass production.
AB  - Biodegradation and biomass production are affected by numerous environmental
      factors including pH, oxygen availability and presence of pollutants. The present
      study, for the first time, elucidated the effects of nutrients and light on
      mycodegradation of petroleum hydrocarbons in diesel oil. Seven fungal strains
      (Aspergillus terreus FA3, Aspergillus niger FA5, Aspergillus terreus FA6,
      Penicillium chrysogenum FP4, Aspergillus terreus FP6, Aspergillus flavus FP10,
      and Candida sp. FG1) were used for hydrocarbon degradation under static
      conditions, in four combinations of nutrient media and illuminance for 45 days.
      Highest degradation was achieved by Aspergillus terreus FA6 and Candida sp. FG1
      under both conditions of light and dark, with nutrient deprived HAF (Hydrocarbon
      adopted fungi) broth. Under HAF/Dark diesel oil degradation by FA6 and FG1 was
      87.3% and 84.3% respectively, while under HAF/Light both FA6 and FG1 performed
      84.3% biodegradation. The highest biomass was produced by Aspergillus flavus FP10
      in PDB (Potato dextrose broth)/Dark (109.3 mg). Fungal degradation of petroleum
      hydrocarbons was negatively affected by the presence of other simpler-to-degrade
      carbon sources in the medium. The biomass production was enhanced by improved
      nutrient availability and diminished by illuminance. 

PMID- 27039365
TI  - One-step synthesis of a novel N-doped microporous biochar derived from crop
      straws with high dye adsorption capacity.
AB  - N-doping is one of the most promising strategies to improve the adsorption
      capacity and selectivity of carbon adsorbents. Herein, synthesis,
      characterization and dye adsorption of a novel N-doped microporous biochar
      derived from direct annealing of crop straws under NH3 is presented. The
      resultant products exhibit high microporosity (71.5%), atomic percentage of
      nitrogen (8.81%), and adsorption capacity to dyes, which is about 15-20 times
      higher than that of original biochar. Specifically, for the sample NBC800-3
      pyrolyzed at 800 degrees C in NH3 for 3 h, its adsorption for acid orange 7 (AO7,
      anionic) and methyl blue (MB, cationic) is up to 292 mg g(-1) and 436 mg g(-1),
      respectively, which is among the highest ever reported for carbonaceous
      adsorbents. The influences of N-doping and porous structure on dye adsorption of
      the synthesized carbons are also discussed, where electrostatic attraction, pi-pi
      electron donor-accepter interaction, and Lewis acid-base interaction mainly
      contribute to AO7 adsorption, and surface area (especially pore-filling)
      dominates MB adsorption. The N-doped biochar can be effectively regenerated and
      reused through direct combustion and desorption approaches.

PMID- 27039366
TI  - The French eco-neighbourhood evaluation model: Contributions to sustainable city
      making and to the evolution of urban practices.
AB  - In this article we discuss whether the French eco-neighbourhood policy tool may
      be considered as an original experimentation in sustainable urban planning. From
      scientific literature across a number of countries and especially in European
      context, we present what kind of policies may achieve eco-neighbourhoods. Then we
      present what the French framework is, and what tools to promote and elaborate eco
      neighbourhoods there are in France. Thirdly, in fact, both French policies,
      national and local, concerning eco-neighbourhood projects, seem to integrate
      means of assessing urban projects and this assessment achieves a kind of
      certification. While the Ministry in charge of Urban Planning has developed the
      national EcoQuartier ("EcoNeighbourhood" in English) certification, the City of
      Paris and other local authorities have designed similar tools, which integrate a
      large number of parameters dealing with urban sustainability and which are
      designed to evolve over time. Finally, we discuss whether the French tool is
      really original and whether it prefigures new practices in the field of
      sustainable urban development. 

PMID- 27039367
TI  - Assessment of dynamic surface leaching of monolithic surface road materials.
AB  - Construction materials have to satisfy, among others, health and environment
      requirements. To check the environmental compatibility of road construction
      materials, release of hazardous substances into water must be assessed.
      Literature mostly describes the leaching behaviour of recycled aggregates for
      potential use in base or sub-base layers of roads. But little is known about the
      release of soluble substances by materials mixed with binders and compacted for
      intended use on road surface. In the present study, we thus performed a diffusion
      test with sequential renewal of water during a 64 day period according to CEN/TS
      16637-2 specifications, on asphalt concretes and hydraulically bound monoliths,
      two common surface road materials. It is shown that release of dangerous
      substances is limited in these hydrodynamic conditions. It was particularly true
      for asphalt concrete leachates where no metallic trace element, sulphate,
      chloride or fluoride ion could be quantified. This is because of the low
      hydraulic conductivity and the low polarity of the petroleum hydrocarbon binder
      of these specimens. For hydraulically bound materials around 20,000 mg/m(2) of
      sulphate diffused from the monoliths. It is one order of magnitude higher than
      chloride diffusion and two orders of magnitude higher than fluoride release. No
      metallic trace element, except small quantities of copper in the last eluate
      could be quantified. No adverse effect is to be expected for human and
      environmental health from the leachates of these compacted surface road
      construction materials, because all the measured parameters were below EU
      (Council Directive 98/83/EC) or WHO guidelines for drinking water standards. 

PMID- 27039368
TI  - Leaching characteristics of encapsulated controlled low-strength materials
      containing arsenic-bearing waste precipitates from refractory gold bioleaching.
AB  - We report on the leaching of heavy elements from cemented waste flowable fill,
      known as controlled low-strength materials (CLSM), for potential mine backfill
      application. Semi-dynamic tank leaching tests were carried out on laboratory
      scale monoliths cured for 28 days and tested over 64 days of leaching with pure
      de-ionised water as leachant. Mineral processing waste include flotation tailings
      from a Spanish nickel-copper sulphide concentrate, and two bioleach
      neutralisation precipitates (from processing at 35 degrees C and 70 degrees C)
      from a South African arsenopyrite concentrate. Encapsulated CLSM formulations
      were evaluated to assess the reduction in leaching by encapsulating a 'hazardous'
      CLSM core within a layer of relatively 'inert' CLSM. The effect of each bioleach
      waste in CLSM core and tailings in CLSM encapsulating medium, are assessed in
      combination and in addition to CLSM with ordinary silica sand. Results show that
      replacing silica sand with tailings, both as core and encapsulating matrix,
      significantly reduced leachability of heavy elements, particularly As (from 0.008
      0.190 mg/l to 0.008-0.060 mg/l), Ba (from 0.435-1.540 mg/l to 0.050-0.565 mg/l),
      and Cr (from 0.006-0.458 mg/l to 0.004-0.229 mg/l), to below the 'Dutch List' of
      groundwater contamination intervention values. Arsenic leaching was inherently
      high from both bioleach precipitates but was significantly reduced to below
      guideline values with encapsulation and replacing silica sand with tailings.
      Tailings proved to be a valuable encapsulating matrix largely owing to small
      particle size and lower hydraulic conductivity reducing diffusion transport of
      heavy elements. Field-scale trials would be necessary to prove this concept of
      encapsulation in terms of scale and construction practicalities, and further
      geochemical investigation to optimise leaching performance. Nevertheless, this
      work substantiates the need for alternative backfill techniques for sustainable
      management of hazardous finely-sized bulk mineral residues.

PMID- 27039369
TI  - Effects of the great recession on drugs consumption in Spain.
AB  - This paper presents evidence on how the consumption of legal and illegal drugs
      has changed in response to the Great Recession in Spain. We use a large scale
      survey from 2005 to 2011 to analyze the association between changes in local
      economic conditions and drug consumption among individuals aged 15-64. Although
      Spain was one of the countries hardest hit by the economic downturn, the crisis
      was unevenly felt across the country. Therefore, we exploit this difference in
      unemployment rates across provinces to identify the effects of business cycle
      variations on the consumption of legal and illegal drugs. To the best of our
      knowledge, this is the first study to find a relation between the deterioration
      of local economic conditions and a strong increase in the consumption of
      marihuana and cocaine. We also report a decrease in alcohol consumption but a
      significant escalation in abusive smoking behavior (smoking every day). We
      believe that these findings are important not only for the potential negative
      implications at the individual level but also for the costs to society as a
      whole.

PMID- 27039370
TI  - EphrinB1 and EphrinB2 regulate T cell chemotaxis and migration in experimental
      autoimmune encephalomyelitis and multiple sclerosis.
AB  - T cells are believed to be key effector cells in multiple sclerosis (MS). In this
      study, we examined the roles of T cell ephrinB1 (EFNB1) and ephrinB2 (EFNB2) in
      the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and MS. We
      provide evidence that animals with T cell specific double deletion of EFNB1 and
      EFNB2 (dKO) have reduced proliferation in response to MOG35-55, defective Th1 and
      Th17 differentiations and significantly lower scores of MOG-induced EAE. We
      further demonstrate that dKO T cells are compromised in their ability to migrate
      into the CNS of EAE animals in vivo and towards multiple chemokines in vitro.
      Using deletion mutations, we identified a critical 11-aa EFNB1 intracellular
      domain segment that controls T cell chemotaxis towards CCL21. In humans, EFNB1
      and EFNB2 are highly expressed in Th1 and Th17 cells and EFNB1- and EFNB2
      expressing T cells are found among immune cell infiltrates in MS lesions. Reverse
      signaling through EFNB1 and EFNB2 in human Th17 cells enhances their migration
      through a monolayer of blood brain barrier endothelial cells. Our study
      demonstrates that expression of EFNB1 and EFNB2 is implicated in Th cell
      differentiation and migration to inflammatory sites in both EAE and MS.

PMID- 27039371
TI  - GWAS and transcriptional analysis prioritize ITPR1 and CNTN4 for a serum uric
      acid 3p26 QTL in Mexican Americans.
AB  - BACKGROUND: The variation in serum uric acid concentrations is under significant
      genetic influence. Elevated SUA concentrations have been linked to increased risk
      for gout, kidney stones, chronic kidney disease, and cardiovascular disease
      whereas reduced serum uric acid concentrations have been linked to multiple
      sclerosis, Parkinson's disease and Alzheimer's disease. Previously, we identified
      a novel locus on chromosome 3p26 affecting serum uric acid concentrations in
      Mexican Americans from San Antonio Family Heart Study. As a follow up, we
      examined genome-wide single nucleotide polymorphism data in an extended cohort of
      1281 Mexican Americans from multigenerational families of the San Antonio Family
      Heart Study and the San Antonio Family Diabetes/Gallbladder Study. We used a
      linear regression-based joint linkage/association test under an additive model of
      allelic effect, while accounting for non-independence among family members via a
      kinship variance component. RESULTS: Univariate genetic analysis indicated serum
      uric acid concentrations to be significant heritable (h (2) = 0.50 +/- 0.05, p <
      4 * 10(-35)), and linkage analysis of serum uric acid concentrations confirmed
      our previous finding of a novel locus on 3p26 (LOD = 4.9, p < 1 * 10(-5)) in the
      extended sample. Additionally, we observed strong association of serum uric acid
      concentrations with variants in following candidate genes in the 3p26 region;
      inositol 1,4,5-trisphosphate receptor, type 1 (ITPR1), contactin 4 (CNTN4),
      decapping mRNA 1A (DCP1A); transglutaminase 4 (TGM4) and rho guanine nucleotide
      exchange factor (GEF) 26 (ARHGEF26) [p < 3 * 10(-7); minor allele frequencies
      ranged between 0.003 and 0.42] and evidence of cis-regulation for ITPR1
      transcripts. CONCLUSION: Our results confirm the importance of the chromosome
      3p26 locus and genetic variants in this region in the regulation of serum uric
      acid concentrations.

PMID- 27039372
TI  - Interaction between COMT rs5993883 and second generation antipsychotics is linked
      to decreases in verbal cognition and cognitive control in bipolar disorder.
AB  - BACKGROUND: Second generation antipsychotics (SGAs) are increasingly utilized in
      Bipolar Disorder (BD) but are potentially associated with cognitive side effects.
      Also linked to cognitive deficits associated with SGA-treatment are catechol-O
      methyltransferase (COMT) gene variants. In this study, we examine the
      relationship between cognition in SGA use and COMT rs5993883 in cohort sample of
      subjects with BD. METHODS: Interactions between SGA-treatment and COMT rs5993883
      genotype on cognition was tested using a battery of neuropsychological tests
      performed in cross-sectional study of 246 bipolar subjects. RESULTS: The mean age
      of our sample was 40.15 years and was comprised of 70 % female subjects.
      Significant demographic differences included gender, hospitalizations,
      benzodiazepine/antidepressant use and BD-type diagnosis. Linear regressions
      showed that the COMT rs5993883 GG genotype predicted lower verbal learning (p =
      0.0006) and memory (p = 0.0026) scores, and lower scores on a cognitive control
      task (p = 0.004) in SGA-treated subjects. Interestingly, COMT GT- or TT-variants
      showed no intergroup cognitive differences. Further analysis revealed an
      interaction between SGA-COMT GG-genotype for verbal learning (p = 0.028), verbal
      memory (p = 0.026) and cognitive control (p = 0.0005). CONCLUSIONS: This
      investigation contributes to previous work demonstrating links between cognition,
      SGA-treatment and COMT rs5993883 in BD subjects. Our analysis shows significant
      associations between cognitive domains such as verbal-cognition and cognitive
      control in SGA-treated subjects carrying the COMT rs5993883 GG-genotype.
      Prospective studies are needed to evaluate the clinical significance of these
      findings.

PMID- 27039373
TI  - Feasibility of four-dimensional preoperative simulation for elbow debridement
      arthroplasty.
AB  - BACKGROUND: Recent advances in imaging modalities have enabled three-dimensional
      preoperative simulation. A four-dimensional preoperative simulation system would
      be useful for debridement arthroplasty of primary degenerative elbow
      osteoarthritis because it would be able to detect the impingement lesions.
      METHODS: We developed a four-dimensional simulation system by adding the
      anatomical axis to the three-dimensional computed tomography scan data of the
      affected arm in one position. Eleven patients with primary degenerative elbow
      osteoarthritis were included. A "two rings" method was used to calculate the
      flexion-extension axis of the elbow by converting the surface of the trochlea and
      capitellum into two rings. A four-dimensional simulation movie was created and
      showed the optimal range of motion and the impingement area requiring excision.
      To evaluate the reliability of the flexion-extension axis, interobserver and
      intraobserver reliabilities regarding the assessment of bony overlap volumes were
      calculated twice for each patient by two authors. Patients were treated by open
      or arthroscopic debridement arthroplasties. Pre- and postoperative examinations
      included elbow range of motion measurement, and completion of the patient-rated
      questionnaire Hand20, Japanese Orthopaedic Association-Japan Elbow Society Elbow
      Function Score, and the Mayo Elbow Performance Score. RESULTS: Measurement of the
      bony overlap volume showed an intraobserver intraclass correlation coefficient of
      0.93 and 0.90, and an interobserver intraclass correlation coefficient of 0.94.
      The mean elbow flexion-extension arc significantly improved from 101 degrees  to
      125 degrees . The mean Hand20 score significantly improved from 52 to 22. The
      mean Japanese Orthopaedic Association-Japan Elbow Society Elbow Function Score
      significantly improved from 67 to 88. The mean Mayo Elbow Performance Score
      significantly improved from 71 to 91 at the final follow-up evaluation.
      CONCLUSION: We showed that four-dimensional, preoperative simulation can be
      generated by adding the rotation axis to the one-position, three-dimensional
      computed tomography image of the affected arm. This method is feasible for elbow
      debridement arthroplasty.

PMID- 27039374
TI  - Load distribution between cephalic screws in a dual lag screw trochanteric nail.
AB  - BACKGROUND: It has been observed clinically that the Z-effect is a potential
      cause of failure of an intramedullary nail with two cephalic screws. It describes
      the migration behavior of the cephalic screws in the femoral head. The primary
      objective was to examine different cephalic screw configurations and test the
      load distribution between them as a function of their relative placement and
      their relative movement in the nail. It has been hypothesized that different
      cephalic screw positions may have an influence on the stress in the implant and
      bone and therefore on implant failures, such as the Z-effect. METHODS: To
      quantify the load distribution of a dual cephalic screw intramedullary femoral
      nail (Citieffe, Calderara di Reno, BO, Italy), a finite element model of the
      femur, focusing on the loading of the cephalic screws, was prepared. Four
      different screw lengths (90-105 mm) were examined. The investigation considered
      the stresses and strains in the bone and implant as well as the relative movement
      of the screws. RESULTS: If the inferior cephalic screw had a shorter length, then
      the superior one and the femoral nail had to bear higher loads. In that case, the
      "equivalent von Mises stress" increased up to 10 % at the superior cephalic screw
      and up to 5 % at the femoral nail. The analysis of the relative movement showed
      that sliding of the inferior cephalic screw occurred in the nail. The total
      movement ranged from 0.47 to 0.73 mm for the different screw configurations.
      CONCLUSIONS: The stresses were distributed more equally between the two cephalic
      screws in the bone and the implant if a longer inferior screw was used. The
      stresses in the bone and implant were reduced with a longer inferior cephalic
      screw. Therefore, a configuration using a longer inferior cephalic screw is
      preferable for trochanteric fracture fixation with a dual cephalic screw
      intramedullary device.

PMID- 27039375
TI  - The association between the duration of fluoropyrimidine-based adjuvant
      chemotherapy and survival in stage II or III gastric cancer.
AB  - BACKGROUND: This study was conducted to propose the optimal duration of
      fluoropyrimidine-based adjuvant chemotherapy consisting of fluoropyrimidine
      derivatives alone or combined with intravenous platinum for stage II or III
      gastric cancer (GC). METHODS: We analyzed retrospectively the data from 2219
      patients with histologically confirmed adenocarcinoma in the stomach, who
      underwent a curative gastrectomy with lymphadenectomy from 2005 to 2012. Five
      year overall survival (OS) and 3-year relapse-free survival (RFS) were analyzed
      according to the duration of fluoropyrimidine-based adjuvant chemotherapy.
      RESULTS: Data from 617 patients with stage II or III GC were analyzable; 187
      patients (30.3%) were treated with surgery alone, while 430 patients (69.7%) were
      treated with postoperative adjuvant chemotherapy. The duration of adjuvant
      chemotherapy was less than 6 months [group 1] in 147 patients (34.2%), 6 months
      to less than 12 months [group 2] in 94 patients (21.9%), 1 year to less than 2
      years [group 3] in 139 patients (32.3%), and over 2 years [group 4] in 50
      patients (11.6%). The 5-year OS in groups 1, 2, 3, and 4 was 75.7, 87, 90.3, and
      93.4%, respectively, while 3-year RFS was 52.5, 58.8, 81.4, and 94.0%,
      respectively. CONCLUSIONS: In this retrospective study, we did not demonstrate
      any significant improvement in OS and RFS by longer periods of fluoropyrimidine
      based adjuvant chemotherapy in stage II or III GCs. Further prospective
      randomized studies are needed.

PMID- 27039376
TI  - Perception of medical professionalism among the surgical community in the
      University of Nairobi: a mixed method study.
AB  - BACKGROUND: Professionalism defines the relationship between colleagues, patients
      and the society as a whole. Furthermore, being a social construct,
      professionalism is sophisticated to be regarded simply as a single concept across
      different cultural contexts. This study sought to explore how professionalism is
      conceptualized by the clinicians, students and patients in a teaching hospital in
      Kenya. METHODS: A sequential mixed methods study was conducted among clinicians,
      students and patients at Kenyatta National Hospital on the surgical wards from
      March 1(st)-December 31(st), 2014. The first phase of the study involved focus
      group discussions (FGDs) of between 10-12 persons and individual in-depth
      interviews of senior faculty and patients. Grounded theory method was used for
      collecting perceptions of participants on professionalism. These views were then
      coded using Atlas 5.2, allowing the development of a questionnaire that provided
      the survey tool for the second phase of the study. For the questionnaire,
      response options utilized a 4-point Likert scale with a range from "strongly
      agree" to "strongly disagree". Factor analysis was used to analyse the responses
      to the survey. Internal reliability was determined by Cronbach's alpha. RESULTS:
      Sixteen FGDs and 18 in-depth interviews were held with 204 clinicians, students
      and patients. A further 188 participants completed the questionnaire. Respect was
      the most frequently mentioned or picked component of professionalism during the
      interview and survey respectively, with 74.5 % of participants reporting
      "strongly agree". Factor analysis showed that 3 factors accounted for the
      majority of the variance in the items analysed; respect in practice, excellence
      in service and concern for the patient. The Cronbach's alpha for this analysis
      was 0.927. CONCLUSION: The study cohort predominantly conceptualizes
      professionalism as relating to respect between colleagues and toward patients.
      Respect, being a cultural norm, should form part of the core curriculum of
      professionalism in order to be relevant for the Kenyan context.

PMID- 27039377
TI  - Work environment, volume of activity and staffing in neonatal intensive care
      units in Italy: results of the SONAR-nurse study.
AB  - BACKGROUND: Neonatal units' volume of activity, and other quantitative and
      qualitative variables, such as staffing, workload, work environment, care
      organization and geographical location, may influence the outcome of high risk
      newborns. Data about the distribution of these variables and their relationships
      among Italian neonatal units are lacking. METHODS: Between March 2010-April 2011,
      63 neonatal intensive care units adhering to the Italian Neonatal Network
      participated in the SONAR Nurse study. Their main features and work environment
      were investigated by questionnaires compiled by the chief and by physicians and
      nurses of each unit. Twelve cross-sectional monthly-repeated surveys on different
      shifts were performed, collecting data on number of nurses on duty and number and
      acuity of hospitalized infants. RESULTS: Six hundred forty five physicians and
      1601 nurses compiled the questionnaires. In the cross-sectional surveys 702
      reports were collected, with 11082 infant and 3226 nurse data points. A high
      variability was found for units' size (4-50 total beds), daily number of patients
      (median 14.5, range 3.4-48.7), number of nurses per shift (median 4.2, range 0.7
      10.8) and number of team meetings per month. Northern regions performed better
      than Central and Southern regions for frequency of training meetings, qualitative
      assessment of performance, motivation within the unit and nursing work
      environment; mean physicians' and nurses' age increased moving from North to
      South. After stratification by terciles of the mean daily number of patients, the
      median number of nurses per shift increased at increasing volume of activity,
      while the opposite was found for the nurse-to-patient ratio adjusted by patients'
      acuity. On average, in units belonging to the lower tercile there was 1 nurse
      every 2.5 patients, while in those belonging to the higher tercile the ratio was
      1 nurse every 5 patients. CONCLUSIONS: In Italy, there is a high variability in
      organizational characteristics and work environment among neonatal units and an
      uneven distribution of human resources in relation to volume of activity,
      suggesting that the larger the unit the greater the workload for each nurse.
      Urgent modifications in planning and organization of services are needed in order
      to pursue more efficient, homogeneous and integrated regionalized neonatal care
      systems.

PMID- 27039378
TI  - Multiple testing correction in linear mixed models.
AB  - BACKGROUND: Multiple hypothesis testing is a major issue in genome-wide
      association studies (GWAS), which often analyze millions of markers. The
      permutation test is considered to be the gold standard in multiple testing
      correction as it accurately takes into account the correlation structure of the
      genome. Recently, the linear mixed model (LMM) has become the standard practice
      in GWAS, addressing issues of population structure and insufficient power.
      However, none of the current multiple testing approaches are applicable to LMM.
      RESULTS: We were able to estimate per-marker thresholds as accurately as the gold
      standard approach in real and simulated datasets, while reducing the time
      required from months to hours. We applied our approach to mouse, yeast, and human
      datasets to demonstrate the accuracy and efficiency of our approach. CONCLUSIONS:
      We provide an efficient and accurate multiple testing correction approach for
      linear mixed models. We further provide an intuition about the relationships
      between per-marker threshold, genetic relatedness, and heritability, based on our
      observations in real data.

PMID- 27039379
TI  - Avian leukosis virus subgroup J induces its receptor--chNHE1 up-regulation.
AB  - BACKGROUND: Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus
      which causes immunosuppression and neoplasia in meat-type and egg-type chickens.
      ALV-J infects host cells via specific interaction between the viral Env and the
      cell surface receptor -chicken sodium hydrogen exchanger type 1 (chNHE1). NHE1
      involved in altering the cellular pH and playing a critical role in
      tumorigenesis. However, little is known about the other relationship between ALV
      J and chNHE1. METHODS AND RESULTS: In ALV-J infected DF-1 cells, the mRNA level
      of chNHE1 was up-regulated with time-dependent manner tested by real time PCR,
      and accordingly, intracellular pH was increased tested by spectrofluorometer. In
      vivo, the mRNA level of chNHE1 was determined by real time PCR in ALV-J infected
      experimental chickens and field cases. The result showed that the mRNA level of
      chNHE1 was up-regulated after virus shedding, especially in continuous viremic
      shedders (CS group). However, no significant difference was found between non
      shedding group (NS group) and control group. In field cases, mRNA level of chNHE1
      was positively correlated with increasing ALV-J load in tumor bearing and immune
      tolerance chickens. Furthermore, immunohistochemistry results showed that the
      protein expression of chNHE1 was up-regulated in different organs of both
      experimental chickens and tumor bearing chickens compared with the control.
      CONCLUSION: Taken together, we conclude that ALV-J induces chNHE1 up-regulation
      in viremia and neoplasia chickens.

PMID- 27039380
TI  - Fruit Odor as A Ripeness Signal for Seed-Dispersing Primates? A Case Study on
      Four Neotropical Plant Species.
AB  - Fleshy fruits contain a myriad of secondary metabolites that may fulfill various
      non-mutually exclusive ecological functions. Among them are defense against
      pathogens and herbivores, manipulation of frugivores' gut retention time, or
      controlling the germination process. In addition, it has been suggested that
      aroma compounds may be used as fruit-selection cues by frugivores, and that
      plants may be under selection to provide a reliable signal for ripeness to seed
      dispersal vectors through ripe fruit aroma. A previous project demonstrated that
      fruit odor of two Neotropical primate-dispersed plant species can be used by
      primates to identify ripe fruits. Here, we provide data supporting the hypothesis
      that olfactory conspicuousness of ripeness in these two species may be an evolved
      signal rather than a cue exploited by primates. We analyzed the odors of ripe and
      unripe fruits of the two species along with odors of two sympatric species whose
      main dispersal vector is passerine birds. We show that only primate-dispersed
      species significantly change their odor profiles upon ripening. Thus, odor of
      bird-dispersed species is not informative regarding their ripeness level and is
      likely to fulfill other functions. We discuss these data in light of the multiple
      hypotheses for the presence of fruit secondary metabolites, and we offer a
      roadmap for future studies to establish the hypothesis that fruit odor is an
      evolved signal for ripeness. 

PMID- 27039381
TI  - Supervised progressive cross-continuum strength training compared with usual care
      in older medical patients: study protocol for a randomized controlled trial (the
      STAND-Cph trial).
AB  - BACKGROUND: Hospitalization in older adults is characterized by physical
      inactivity and a risk of losing function and independence. Systematic strength
      training can improve muscle strength and functional performance in older adults.
      Few studies have examined the effect of a program initiated during
      hospitalization and continued after discharge. We conducted a feasibility study
      prior to this trial and found a progression model for loaded sit-to-stands
      feasible in older medical patients. This study aims to determine whether a simple
      supervised strength training program for the lower extremities (based on the
      model), combined with post-training protein supplementation initiated during
      hospitalization and continued at home for 4 weeks, is superior to usual care on
      change in mobility 4 weeks after discharge in older medical patients. METHODS:
      Eighty older medical patients (65 years or older) acutely admitted from their own
      homes will be included in this randomized, controlled, parallel-group,
      investigator-blinded, superiority trial. After baseline assessments patients will
      be randomized to (1) intervention: progressive strength training during
      hospitalization and after discharge (home-based), or (2) control: usual care.
      Shortly after discharge, 4 weeks after discharge (primary end point) and 6 months
      after discharge patients will be assessed in their own homes. The intervention
      encompasses strength training consisting of two lower extremity exercises (sit-to
      stand and heel raise) daily during hospitalization and three times per week for 4
      weeks after discharge. Both exercises follow pre-defined models for progression
      and will be performed for three sets of 8-12 repetitions maximum in each training
      session. Thereafter, the patient will be asked to consume a protein supplement
      given orally containing 18 g milk-based protein. The primary outcome will be
      change in the de Morton Mobility Index score from baseline to 4 weeks after
      discharge. Secondary outcomes will be 24-h mobility level, isometric knee
      extension strength, the 30-sec sit-to-stand test, habitual gait speed, hand-grip
      strength, and Activities of Daily Living. DISCUSSION: We chose to investigate the
      effect of a minimal time-consuming treatment approach, i.e. two well-performed
      strength training exercises combined with protein supplementation, to facilitate
      implementation in a busy clinical care setting, given a positive trial outcome.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01964482 .

PMID- 27039382
TI  - Association between biomarkers of tissue inflammation and progression of
      osteoarthritis: evidence from the Rotterdam study cohort.
AB  - BACKGROUND: We aimed to investigate the prognostic value of two biomarkers of
      tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive
      protein (CRPM) and connective tissue type I collagen turnover (C1M), on the
      incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam
      Study, a prospective cohort. Moreover, the independent effect of these biomarkers
      with respect to the established biomarkers of OA progression, like urinary type
      II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP),
      was evaluated. METHODS: Serum levels of C1M, CRPM, COMP and CRP of 1335
      participants aged >55 years were measured in fasting serum using ELISA. The
      commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and
      5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The
      associations between progression and incidence of OA and the baseline biomarkers
      were examined using logistic regression and generalized estimating equations
      adjusted for age, sex, BMI, and possible other confounders. RESULTS: The uCTX-II,
      COMP, and CRP concentrations were associated with the incidence and progression
      of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p
      = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II
      (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for
      progression of OA independent from the uCTX-II and COMP. CONCLUSIONS: Our study
      confirmed the associations between uCTX-II and COMP concentrations and OA
      progression. Importantly, we showed for the first time that CRPM predicts the
      risk of OA progression independent of the established biomarkers uCTX-II and
      COMP.

PMID- 27039383
TI  - Effects of milk containing only A2 beta casein versus milk containing both A1 and
      A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort,
      and cognitive behavior of people with self-reported intolerance to traditional
      cows' milk.
AB  - BACKGROUND: Cows' milk generally contains two types of beta-casein, A1 and A2
      types. Digestion of A1 type can yield the peptide beta-casomorphin-7, which is
      implicated in adverse gastrointestinal effects of milk consumption, some of which
      resemble those in lactose intolerance. This study aimed to compare the effects of
      milk containing A1 beta-casein with those of milk containing only A2 beta-casein
      on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive
      processing in subjects with self-reported lactose intolerance. METHODS: Forty
      five Han Chinese subjects participated in this double-blind, randomized, 2 * 2
      crossover trial and consumed milk containing both beta-casein types or milk
      containing only A2 beta-casein. Each treatment period was 14 days with a 14-day
      washout period at baseline and between treatment periods. Outcomes included PD3,
      gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment
      Test (SCIT), serum/fecal laboratory biomarkers, and adverse events. RESULTS:
      Compared with milk containing only A2 beta-casein, the consumption of milk
      containing both beta-casein types was associated with significantly greater PD3
      symptoms; higher concentrations of inflammation-related biomarkers and beta
      casomorphin-7; longer gastrointestinal transit times and lower levels of short
      chain fatty acids; and increased response time and error rate on the SCIT.
      Consumption of milk containing both beta-casein types was associated with
      worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose
      intolerant subjects. Consumption of milk containing only A2 beta-casein did not
      aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy
      products) in lactose tolerant and intolerant subjects. CONCLUSIONS: Consumption
      of milk containing A1 beta-casein was associated with increased gastrointestinal
      inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive
      processing speed and accuracy. Because elimination of A1 beta-casein attenuated
      these effects, some symptoms of lactose intolerance may stem from inflammation it
      triggers, and can be avoided by consuming milk containing only the A2 type of
      beta casein. TRIAL REGISTRATION: ClinicalTrials.gov/NCT02406469.

PMID- 27039385
TI  - Erratum to: Piloting a new approach in primary care to identify, assess and
      support carers of people with terminal illnesses: a feasibility study.

PMID- 27039384
TI  - Verification of microRNA expression in human endometrial adenocarcinoma.
AB  - BACKGROUND: MicroRNAs are small non-coding RNAs that have been implicated in
      tumor initiation and progression. In a previous study we identified 138 miRNAs as
      differentially expressed in endometrial adenocarcinoma compared to normal
      tissues. One of these miRNAs was miRNA-34a, which regulates several genes
      involved in the Notch pathway, which is frequently altered in endometrial cancer.
      The aims of this study were to verify the differential expression of a subset of
      miRNAs and to scrutinize the regulatory role of mir-34a on the target genes
      NOTCH1 and DLL1. METHODS: Twenty-five miRNAs that were previously identified as
      differentially expressed were subjected to further analysis using qPCR. To
      investigate the regulation of NOTCH1 and DLL1 by mir-34a, we designed gain- and
      loss-of-function experiments in Ishikawa and HEK293 cell lines by transfection
      with a synthetic mir-34a mimic and a mir-34a inhibitor. RESULTS: Of the 25
      validated miRNAs, seven were down-regulated and 18 were up-regulated compared to
      normal endometrium, which was fully consistent with our previous findings. In
      addition, the up-regulation of mir-34a led to a significant decrease in mRNA
      levels of NOTCH1 and DLL1, while down-regulation led to a significant increase in
      mRNA levels of these two genes. CONCLUSIONS: We verified both up-regulated and
      down-regulated miRNAs in the tumor samples, indicating various roles of microRNAs
      during tumor development. Mir-34a functions as a regulator by decreasing the
      expression of NOTCH1 and DLL1. Our study is the first to identify a correlation
      between mir-34a and its target genes NOTCH1 and DLL1 in endometrial
      adenocarcinoma.

PMID- 27039386
TI  - A phase I, dose escalation, pharmacodynamic, pharmacokinetic, and food-effect
      study of alpha2 integrin inhibitor E7820 in patients with advanced solid tumors.
AB  - Introduction E7820 is an orally administered sulfonamide that inhibits alfa-2
      integrin mRNA expression. Pre-clinically E7820 showed tumor anti-angiogenic
      effects in various tumor cell lines and xenograft mouse models. Human daily
      dosing of 100 mg QD had previously been shown to be safe and tolerable. Methods
      The study consisted of two parts: Part A (food effect) and Part B (determination
      of maximum tolerated dose (MTD) for bi-daily (BID) dosing). E7820 dosing started
      at 50 mg BID with planned escalation to 60, 80 and 100 mg BID every 28 days.
      Results Fifteen patients were enrolled in Part A and 26 in Part B. The most
      frequent adverse events of all grades were constipation, diarrhea, nausea, and
      fatigue while anemia, neutropenia, and fatigue were most frequent grade >=3
      toxicities. At dose-level 60 mg BID, two patients experienced dose-limiting
      toxicities (grade 3 neutropenic sepsis and grade 4 neutropenia). Therefore the
      recommended dose (RD) was 50 mg BID. Food had no effect on E7820 exposure. E7820
      exposure following twice daily administration was dose-proportional. Expression
      of platelet integrin-alpha2 measured as a response biomarker in Part B, generally
      decreased by a median 7.7 % from baseline following treatment with 50 mg BID
      E7820. Reduction was most pronounced within 1-week post treatment. The median
      duration of treatment was median 54, range 20-111 days. The best overall response
      in any treatment group was stable disease (SD): 23.1 % in Part A (100 mg QD); at
      the RD 66.7 % (12 of 18 patients) and 40 % in the 60 mg BID group in Part B.
      CONCLUSIONS: Food had no effect on E7820 exposure. A dose of 50 mg BID was
      considered the MTD. Treatment with E7820 is safe and tolerable with 2/3 of
      patients (66.7 %) at MTD having SD as their best response.

PMID- 27039387
TI  - Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome
      inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3
      maintenance study.
AB  - Background Ixazomib is the first oral, small molecule proteasome inhibitor to
      reach phase 3 trials. The current analysis characterized the exposure-safety and
      exposure-efficacy relationships of ixazomib in patients with relapsed/refractory
      multiple myeloma (MM) with a purpose of recommending an approach to ixazomib
      dosing for maintenance therapy. Methods Logistic regression was used to
      investigate relationships between ixazomib plasma exposure (area under the
      curve/day; derived from individual apparent clearance values from a published
      population pharmacokinetic analysis) and safety/efficacy outcomes (hematologic
      [grade >= 3 vs <= 2] or non-hematologic [grade >= 2 vs <= 1] adverse events
      [AEs], and clinical benefit [>=stable disease vs progressive disease]) using
      phase 1 data in relapsed/refractory MM (NCT00963820; N = 44). Results Significant
      relationships to ixazomib exposure were observed for five AEs (neutropenia,
      thrombocytopenia, rash, fatigue, and diarrhea) and clinical benefit (p < 0.05).
      Dose-response relationships indicated a favorable benefit/risk ratio at 3 mg and
      4 mg weekly, which are below the maximum tolerated dose of 5.5 mg. At 3 mg, the
      model predicted that: 37 % of patients will achieve clinical benefit; incidence
      of grade >= 3 neutropenia and thrombocytopenia will be 10 % and 23 %,
      respectively; and incidence of grade >= 2 rash, fatigue, and diarrhea will be 8
      %, 19 %, and 19 %, respectively. Conclusions Based on the findings, patients in
      the phase 3 maintenance trial will initiate ixazomib at a once-weekly dose of 3
      mg, increasing to 4 mg if acceptable tolerability after 4 cycles, to provide
      maximum clinical benefit balanced with adequate tolerability.

PMID- 27039388
TI  - Plasmapheresis and immunoadsorption in patients with steroid refractory multiple
      sclerosis relapses.
AB  - Patients suffering from multiple sclerosis (MS) are treated with high-dose
      intravenous steroids during acute relapses. In case of steroid refractory
      relapses, patients are treated with plasmapheresis or immunoadsorption. Until now
      data concerning the efficacy of both procedures are scarce. Visual evoked
      potentials (VEP), visual acuity and degree of remission of deficits caused by a
      relapse that had led to admission in MS patients (n = 48) treated with PLEX, IA
      or both in a single university centre setting were evaluated retrospectively. In
      a grouped analysis of patients treated with combined PLEX/IA, PLEX or IA alone,
      patients in all groups profited as assessed by VEP. Visual acuity also showed a
      trend towards a better performance, but lacked significance. In a subgroup
      analysis only concerning patients with initially pathological VEP there was a
      significant beneficial effect in the groups treated with PLEX/IA as well as in
      the group summarizing all patients. The combination of PLEX and IA provides a
      valid treatment option in steroid-refractory MS-relapses, and IA should be
      considered in acute relapses especially in patients with side effect of PLEX. 

PMID- 27039389
TI  - Women have a poorer very long-term functional outcome after stroke among adults
      aged 18-50 years: the FUTURE study.
AB  - Due to their young age young stroke survivors have to cope with a dramatic impact
      on their life for the decades to come. We investigated the sex-specific very long
      term functional outcome after transient ischemic attack (TIA) and ischemic stroke
      (IS) in adults aged 18-50 years. This study is part of a cohort study among 619
      first-ever young ischemic stroke patients, admitted to our department between
      January 1, 1980 and November 1, 2010. Functional outcome was assessed during
      follow-up in 2009-2011 and in 2014-2015 with the modified Rankin Scale (mRS) and
      instrumental Activities of Daily Living scale (iADL). Risk factors for a poor
      functional outcome (mRS > 2 and iADL < 8) were calculated by logistic regression
      analysis. After a mean follow-up of 13.9 (SD 8.2) years, 24.5 % of TIA patients
      and 44.7 % of IS patients had a poor functional outcome (mRS > 2). When assessing
      the survivors, 15.2 % of TIA patients and 22.9 % of IS patients had a poor
      outcome as assessed by iADL. The strongest baseline predictors of poor outcome
      were female sex (OR 2.7, 95 % CI 1.5-5.0) and baseline NIHSS (OR 1.1, 95 % CI 1.1
      1.2 per point increase). In conclusion, 14 years after an ischemic
      cerebrovascular event in young adults, one out of five IS survivors and one out
      of ten TIA survivors is still dependent in daily life, with a two to threefold
      higher risk of a poor outcome in women. This includes a period of life, during
      which important decisions regarding work and family life have to be made. 

PMID- 27039390
TI  - Ice cream headache in students and family history of headache: a cross-sectional
      epidemiological study.
AB  - Headache attributed to ingestion of a cold stimulus (ICHD-3 beta 4.5.1) is also
      known as ice cream headache (ICH). This cross-sectional epidemiological study
      included 283 students (10-14-year-olds) attending a grammar school in Germany,
      their parents (n = 401), and 41 teachers. A self-administered questionnaire was
      used to analyze the prevalence and characteristics of ICH based on the ICHD
      classification. Additionally, the association between ICH and other headaches was
      investigated in students and parents. Prevalence of ICH in students was 62 %
      without gender difference. In adults, only 36 % of females and 22 % of males
      reported ICH. There was an increased risk for ICH in students when mother (OR
      10.7) or father (OR 8.4) had ICH. Other headaches in parents had no influence on
      the prevalence of ICH in students. However, in the groups of students and parents
      itself there was a highly significant association between ICH and other headaches
      (students: OR 2.4, mothers: OR 2.9, fathers: OR 6.8). There was a decreased risk
      for ICH when parents and students had no headache at all (OR < 0.4). ICH in
      students clearly shows a familial disposition by both father and mother. There
      was also an association between ICH and other headaches within the student and
      adult groups. The absence of headache history seems to be a protective factor for
      ICH. 

PMID- 27039391
TI  - Lucja Frey (1889-1942).

PMID- 27039392
TI  - Pearls and Pitfalls in Diagnosing IgE-Mediated Food Allergy.
AB  - The term "food allergy" is used by many patients and clinicians to describe a
      range of symptoms that occur after ingestion of specific foods. However, not all
      symptoms occurring after food exposure are due to an allergic, or immunologic,
      response. It is important to properly evaluate and diagnose immunoglobulin E
      (IgE)-mediated food allergy as this results in reproducible, immediate onset,
      allergic reactions that can progress toward life-threatening anaphylaxis. Proper
      diagnosis requires understanding of the common foods that cause these reactions
      in addition to key historical elements such as symptoms, timing and duration of
      reaction, and risk factors that may predispose to development of IgE-mediated
      food allergy. Diagnostic testing for food-specific IgE can greatly aid the
      diagnosis. However, false-positive test results are very common and can lead to
      overinterpretation, misdiagnosis, and unnecessary dietary elimination. This
      review discusses important aspects to consider during evaluation of a patient for
      suspected IgE-mediated food allergy. 

PMID- 27039393
TI  - Peanut Allergy: New Developments and Clinical Implications.
AB  - Food allergies have increased in prevalence over the past 20 years, now becoming
      an important public health concern. Although there are no therapies currently
      available for routine clinical care, recent reports have indicated that
      immunotherapies targeting the mucosal immune system may be effective. Oral
      immunotherapy is conducted by administering small, increasing amounts of food
      allergen; it has shown promise for desensitizing individuals with peanut, egg, or
      milk allergies. Sublingual immunotherapy also desensitizes allergic patients to
      foods-two major studies have examined the effects of sublingual immunotherapy in
      subjects with peanut allergies. We review the complex nature of IgE-mediated food
      allergies and the therapies being evaluated in clinical trials. We focus on the
      diagnosis and management of food allergies and investigational therapies. 

PMID- 27039394
TI  - Epigenetic Dysfunction in Turner Syndrome Immune Cells.
AB  - Turner syndrome (TS) is a chromosomal condition associated with partial or
      complete absence of the X chromosome that involves characteristic findings in
      multiple organ systems. In addition to well-known clinical characteristics such
      as short stature and gonadal failure, TS is also associated with T cell immune
      alterations and chronic otitis media, suggestive of a possible immune deficiency.
      Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome
      (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a
      downregulated gene in TS immune cells. Importantly, UTX is an X-linked gene that
      escapes X-chromosome inactivation and thus is haploinsufficient in TS. Mice with
      T cell-specific UTX deficiency have impaired clearance of chronic viral infection
      due to decreased frequencies of T follicular helper (Tfh) cells, which are
      critical for B cell antibody generation. In parallel, TS patients have decreased
      Tfh frequencies in peripheral blood. Together, these findings suggest that
      haploinsufficiency of the X-linked UTX gene in TS T cells underlies an immune
      deficit, which may manifest as increased predisposition to chronic otitis media. 

PMID- 27039395
TI  - Distal humerus fractures: a review of current therapy concepts.
AB  - Fractures of the distal humerus in the adult comprise approximately one third of
      all humeral fractures. Successful management of distal humerus fractures depends
      on correct reduction of the fracture, reconstruction of the articular surface if
      needed, stability and rigidity of the fixation, and appropriate rehabilitation.
      In this review, we evaluated the available literature and highlighted current
      therapy concepts. We assessed the evolution of internal fixation and elbow
      arthroplasty focusing on the established surgical approaches against the
      background of a growing incidence of distal humeral fractures in an aging patient
      population. Therefore evaluating the aspect and influence of age-dependent
      comorbidities like osteoporosis on successful treatment. 

PMID- 27039396
TI  - Primaquine plus artemisinin combination therapy for reduction of malaria
      transmission: promise and risk.
AB  - Reduction of gametocyte transmission from humans to mosquitoes is a key component
      of malaria elimination. The study by Goncalves and colleagues provides valuable
      new data on how the addition of low-dose primaquine to artemether-lumefantrine
      affects reduction of gametocytemia and transmission of gametocytes to mosquitoes
      in asymptomatically Plasmodium falciparum-infected children without G6PD
      deficiency, and on the degree to which low-dose primaquine affects hemoglobin
      levels in these children. The study sets the stage for future research required
      for consideration of an artemisinin combination therapy (ACT)-primaquine regimen
      in mass drug administration campaigns. Future studies will need to evaluate
      toxicity in adults and G6PD deficient persons, assess gametocyte transmission
      from adults, evaluate different ACT drugs with primaquine, and assess the
      implications of "rare" toxicities in large treatment populations, such as
      hemolysis requiring blood transfusion. The study highlights both the promise and
      the potential risk of ACT-primaquine treatment in malaria elimination
      campaigns.Please see related article:
      https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0581-y . 

PMID- 27039397
TI  - 25-methoxyl-dammarane-3beta, 12beta, 20-triol and artemisinin synergistically
      inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific
      protease 50 (TSP50) expression.
AB  - While the incidence of cancer continues to increase, the current therapeutic
      options remain imperfect. Therefore, there is an urgent need to discover new
      targeted anti-cancer therapies. Testes-specific protease 50 (TSP50) is abnormally
      expressed in most cancer tissues and downregulation of TSP50 expression can
      reduce cell proliferation and induce cell apoptosis, which makes it a potential
      target for cancer therapy. In this study, we constructed a firefly luciferase
      reporter pGL3-TSP50-3'-UTR as a drug screening model to screen potential
      candidate compounds that target TSP50 mRNA. We identified the compound 7P3A,
      which consists of 70 % 25-methoxyl-dammarane-3beta, 12beta, 20-triol and 30 %
      artemisinin, as being capable of inhibiting the TSP50-3'-UTR reporter activity,
      as well as the expression of TSP50. Further investigation revealed that 7P3A
      could inhibit MDA-MB-231 cell proliferation and induce cell cycle arrest, and
      over-expression of TSP50 partially reversed the effect of 7P3A. In vivo
      investigation showed that 7P3A could inhibit tumor growth in a xenograft model of
      breast cancer. These results suggest that 7P3A exhibits anti-cancer effects, in
      part, through downregulation of TSP50 expression.

PMID- 27039398
TI  - The role of microRNA-26a in human cancer progression and clinical application.
AB  - MicroRNAs, a class of endogenous, small (18-25 nucleotides) noncoding RNAs,
      regulate gene expression by directly binding to the 3'-untranslated regions of
      target messenger RNAs. Evidence has shown that alteration of microRNAs is
      involved in cancer initial and progression. MicroRNA-26a is commonly dysregulated
      in diverse cancers and is involved in various biological processes, including
      proliferation, migration, invasion, angiogenesis, and metabolism by targeting
      multiple mRNAs. This review summarizes current research on the physiology and
      pathological functions of miR-26a and its applications for clinical therapy. 

PMID- 27039399
TI  - Inhibition of Bacterial Toxin Activity by the Nuclear Stain, DRAQ5TM.
AB  - The repeats-in-toxin family of toxins includes proteins produced by Gram negative
      bacteria such as Escherichia coli (alpha-hemolysin), Bordetella pertussis
      (adenylate cyclase toxin), and Aggregatibacter actinomycetemcomitans (LtxA),
      which contribute to the pathogenesis of these organisms by killing host cells. In
      the case of LtxA produced by A. actinomycetemcomitans, white blood cells are
      targeted, allowing the bacteria to avoid clearance by the host immune system. In
      its association with target cells, LtxA binds to a receptor, lymphocyte function
      associated antigen-1, as well as membrane lipids and cholesterol, before being
      internalized via a lysosomal-mediated pathway. The motivation for this project
      comes from our discovery that DRAQ5TM, a membrane-permeable nuclear stain,
      prevents the internalization of LtxA in a Jurkat T cell line. We hypothesized
      that DRAQ5TM, in crossing the plasma membrane, alters the properties of the
      membrane to inhibit LtxA internalization. To investigate how DRAQ5TM interacts
      with the lipid membrane to prevent LtxA internalization, we used studied DRAQ5TM
      mediated membrane changes in model membranes using a variety of techniques,
      including differential scanning calorimetry and fluorescence spectroscopy. Our
      results suggest that DRAQ5TM inhibits the activity of LtxA by decreasing the
      fluidity of the cellular lipid membrane, which decreases LtxA binding. These
      results present an interesting possible anti-virulence strategy; by altering
      bacterial toxin activity by modifying membrane fluidity, it may be possible to
      inhibit the pathogenicity of A. actinomycetemcomitans.

PMID- 27039400
TI  - The Effect of Ionic Liquid Pretreatment on the Bioconversion of Tomato Processing
      Waste to Fermentable Sugars and Biogas.
AB  - Tomato pomace is an abundant lignocellulosic waste stream from industrial tomato
      processing and therefore a potential feedstock for production of renewable
      biofuels. However, little research has been conducted to determine if
      pretreatment can enhance release of fermentable sugars from tomato pomace. Ionic
      liquids (ILs) are an emerging pretreatment technology for lignocellulosic biomass
      to increase enzymatic digestibility and biofuel yield while utilizing recyclable
      chemicals with low toxicity. In this study, pretreatment of tomato pomace with
      the ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) was
      investigated. Changes in pomace enzymatic digestibility were affected by
      pretreatment time and temperature. Certain pretreatment conditions significantly
      improved reducing sugar yield and hydrolysis time compared to untreated pomace.
      Compositional analyses suggested that pretreatment primarily removed water
      soluble compounds and enriched for lignocellulose in pomace, with only subtle
      changes to the composition of the lignocellulose. While tomato pomace was
      effectively pretreated with [C2mim][OAc] to improve enzymatic digestibility, as
      of yet, unknown factors in the pomace caused ionic liquid pretreatment to
      negatively affect anaerobic digestion of pretreated material. This result, which
      is unique compared to similar studies on IL pretreatment of grasses and woody
      biomass, highlights the need for additional research to determine how the unique
      chemical composition of tomato pomace and other lignocellulosic fruit residues
      may interact with ionic liquids to generate inhibitors for downstream
      fermentation to biofuels. 

PMID- 27039401
TI  - Enhancement of Echinocandin B Production by a UV- and Microwave-Induced Mutant of
      Aspergillus nidulans with Precursor- and Biotin-Supplying Strategy.
AB  - Echinocandin B belongs to lipopeptide antifungal antibiotic bearing five types of
      direct precursor amino acids including proline, ornithine, tyrosine, threonine,
      and leucine. The objective of this study is to screen over-producing mutant in
      order to improve echinocandin B production; a stable mutant Aspergillus nidulans
      ZJB12073, which can use fructose as optimal carbon source instead of expensive
      mannitol, was selected from thousand isolates after several cycles of UV and
      microwave irradiation in turn. The results showed that mutant strain ZJB12073
      exhibited 1.9-fold improvement in echinocandin B production to 1656.3 +/- 40.3
      mg/L when compared with the parent strain. Furthermore, the effects of precursor
      amino acids and some chemicals on echinocandin B biosynthesis in A. nidulans were
      investigated, respectively. Tyrosine, leucine, and biotin were selected as key
      factors to optimize the medium employing uniform design method. The results
      showed that the optimized fermentation medium provided another 63.1 % increase to
      2701.6 +/- 31.7 mg/L in final echinocandin B concentration compared to that of
      unoptimized medium. 

PMID- 27039402
TI  - Feasibility of A-mode ultrasound attenuation as a monitoring method of local
      hyperthermia treatment.
AB  - Recently, there is an increasing interest in the use of local hyperthermia
      treatment for a variety of clinical applications. The desired therapeutic outcome
      in local hyperthermia treatment is achieved by raising the local temperature to
      surpass the tissue coagulation threshold, resulting in tissue necrosis. In
      oncology, local hyperthermia is used as an effective way to destroy cancerous
      tissues and is said to have the potential to replace conventional treatment
      regime like surgery, chemotherapy or radiotherapy. However, the inability to
      closely monitor temperature elevations from hyperthermia treatment in real time
      with high accuracy continues to limit its clinical applicability. Local
      hyperthermia treatment requires real-time monitoring system to observe the
      progression of the destroyed tissue during and after the treatment. Ultrasound is
      one of the modalities that have great potential for local hyperthermia
      monitoring, as it is non-ionizing, convenient and has relatively simple signal
      processing requirement compared to magnetic resonance imaging and computed
      tomography. In a two-dimensional ultrasound imaging system, changes in tissue
      microstructure during local hyperthermia treatment are observed in terms of pixel
      value analysis extracted from the ultrasound image itself. Although 2D ultrasound
      has shown to be the most widely used system for monitoring hyperthermia in
      ultrasound imaging family, 1D ultrasound on the other hand could offer a real
      time monitoring and the method enables quantitative measurement to be conducted
      faster and with simpler measurement instrument. Therefore, this paper proposes a
      new local hyperthermia monitoring method that is based on one-dimensional
      ultrasound. Specifically, the study investigates the effect of ultrasound
      attenuation in normal and pathological breast tissue when the temperature in
      tissue is varied between 37 and 65  degrees C during local hyperthermia
      treatment. Besides that, the total protein content measurement was also conducted
      to investigate the relationship between attenuation and tissue denaturation level
      at different temperature ranges. The tissues were grouped according to their
      histology results, namely normal tissue with large predominance of cells (NPC),
      cancer tissue with large predominance of cells (CPC) and cancer with high
      collagen fiber content (CHF). The result shows that the attenuation coefficient
      of ultrasound measured following the local hyperthermia treatment increases with
      the increment of collagen fiber content in tissue as the CHF attenuated
      ultrasound at the highest rate, followed by NPC and CPC. Additionally, the
      attenuation increment is more pronounced at the temperature over 55  degrees C.
      This describes that the ultrasound wave experienced more energy loss when it
      propagates through a heated tissue as the tissue structure changes due to protein
      coagulation effect. Additionally, a significant increase in the sensitivity of
      attenuation to protein denaturation is also observed with the highest sensitivity
      obtained in monitoring NPC. Overall, it is concluded that one-dimensional
      ultrasound can be used as a monitoring method of local hyperthermia since its
      attenuation is very sensitive to the changes in tissue microstructure during
      hyperthermia. 

PMID- 27039403
TI  - Preoperative neuropsychological presentation of patients with refractory frontal
      lobe epilepsy.
AB  - BACKGROUND: This study investigated whether certain cognitive deficits are
      associated with frontal lobe epilepsy (FLE) aiming to contribute with
      localization data to the preoperative assessment of epilepsy surgery candidates.
      METHODS: We evaluated 34 patients with refractory FLE, 37 patients with
      refractory medial temporal lobe epilepsy (MTLE), and 22 healthy individuals in
      attention, psychomotor speed, motor function, verbal memory span, verbal fluency,
      response inhibition/interference, concept formation and set shifting,
      anticipation and planning, global memory. RESULTS: Neuropsychological
      performances of FLE and MTLE were similar, with the only exception the WCST
      number of categories index, measuring mental flexibility, in which MTLE patients
      performed significantly worse than FLE patients. Left-FLE patients presented more
      perseverative responding compared to both other patient groups and healthy
      controls (HCs), while left-MTLE patients showed worse sorting abilities than the
      other epilepsy groups. CONCLUSIONS: Our findings suggest a weak cognitive
      differentiation between FLE and MTLE, probably attributed to the intricate nature
      of fronto-temporal connectivity frequently resulting in overlapping deficits as
      well as the confounding effects of seizure-related variables. In clinical
      practice, a highly individualized (idiographic) neuropsychological approach along
      with the inclusion of concurrent EEG recordings (e.g., interictal coupling) may
      be of help for neuropsychologists in identifying FLE patients from those with
      medial temporal pathology presenting frontal dysfunction as a secondary cognitive
      symptom.

PMID- 27039404
TI  - Anticoagulants and antiplatelet agents for preventing central venous
      haemodialysis catheter malfunction in patients with end-stage kidney disease.
AB  - BACKGROUND: Catheter malfunction, including thrombosis, is associated with
      reduced dialysis adequacy, as well as an increased risk of catheter-related
      bacteraemia and mortality. The role of anticoagulants in the prevention of
      catheter malfunction remains uncertain. OBJECTIVES: This review aimed to compare
      the prophylactic effect of different anticoagulant agents, preparations, doses
      and administration on the incidence of central venous haemodialysis catheter
      related malfunction and sepsis in patients with end-stage kidney disease (ESKD).
      SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 7
      January 2016 through contact with the Trials' Search Co-ordinator using search
      terms relevant to this review. SELECTION CRITERIA: We included all randomised
      controlled trials (RCT) assessing anticoagulants compared with conventional care
      for the prevention of catheter malfunction in adult patients receiving
      haemodialysis for ESKD. DATA COLLECTION AND ANALYSIS: The primary outcome was
      catheter malfunction defined as a catheter blood flow of 200 mL/min or less, or
      as defined by study authors. Secondary outcomes were catheter-related
      bacteraemia, all-cause mortality and bleeding events. Relative risks (RR) with
      95% confidence intervals (CI) for individual studies were pooled using random
      effects models within treatment classes. Analyses were conducted by class, with
      subgroup analyses performed of individual agents within classes. MAIN RESULTS: We
      included 27 studies (3003 participants) that were followed up for a median of six
      months. Study interventions included alternative anticoagulant locking solutions
      (19 studies, 2216 patients), systemic agents (6 studies, 664 patients) and low or
      no dose heparin (2 studies, 123 patients). The most common comparison treatment
      was a locking solution of heparin 5000 IU/mL, used in 17 studies. No significant
      effect on catheter malfunction was observed for alternative anticoagulant locking
      solutions (RR 0.96, 95% CI 0.74 to 1.26), systemic agents (RR 0.59, 95% CI 0.28
      to 1.23), or low or no dose heparin (RR 0.90, 95% CI 0.10 to 8.31). A significant
      reduction on incidence of catheter-related bacteraemia was observed for
      alternative anticoagulant locking solutions (RR 0.46, 95% CI 0.32 to 0.66) but
      not systemic agents (RR 2.41, 95% CI 0.89 to 6.55), and could not be assessed in
      reports of low or no dose heparin studies. No significant effect on all-cause
      mortality was observed for alternative anticoagulant locking solutions (RR 0.88,
      95% CI 0.54 to 1.43) or systemic agents (RR 0.78, 95% CI 0.37 to 1.65), and was
      not reported in studies of low or no dose heparin. Bleeding events were only
      reported in eight studies, including only 2/5 studies of systemic warfarin, with
      no clear effect demonstrated (RR 1.43, 95% CI 0.86 to 2.39). For individual
      agents, recombinant tissue plasminogen (rt-PA) was the only locking solution
      shown to reduce catheter malfunction (RR 0.58, 95% CI 0.37 to 0.91) based on the
      results of a single study. No significant on catheter malfunction was observed
      for other individual classes of alternative anticoagulant locking solutions
      (citrate: RR 1.14, 95% CI 0.76 to 1.69; antibiotic: RR 1.48, 95% CI 0.79 to 2.77;
      ethanol: RR 0.88, 95% CI 0.21 to 3.67). On the other hand, all individual classes
      of alternative anticoagulant locking solutions, except ethanol, reduced catheter
      related bacteraemia (citrate: RR 0.49, 95% CI 0.36 to 0.68; antibiotic: RR 0.27,
      95% CI 0.11 to 0.70; rt-PA: RR 0.35, 95% CI 0.13 to 0.93; ethanol: RR 0.33, 95%
      CI 0.03 to 4.05). No significant effect on all-cause mortality was observed for
      any individual agent within the class of alternative locking solutions. Studies
      were mainly of low quality and underpowered with an average participant number of
      75 and study duration of six months. The interpretation of the study evidence was
      further limited by the variation in tested interventions and outcome reporting.
      AUTHORS' CONCLUSIONS: The relative net benefit of anticoagulant therapies for
      prevention of catheter malfunction remains uncertain. Multiple agents appear to
      reduce catheter-related bacteraemia although the lack of clear assessment of
      harms and the limitations of study quality mean these results should be
      interpreted with caution. Methodological approaches can be used to avoid methods
      of reporting unduly affecting on the results of meta-analyses incorporating
      studies employed mixed reporting methods. Further high quality randomised
      studies, including safety outcomes, are needed.

PMID- 27039405
TI  - [Current topics of myocardia regeneration].

PMID- 27039406
TI  - [Diagnosis and treatment for refractory otitis].

PMID- 27039407
TI  - [Treatment for refractory nose bleeding].

PMID- 27039408
TI  - [Practice guideline for pediatric secretory otitis].

PMID- 27039409
TI  - Supplemental Nutrition Assistance Program: Nutrition Education   and Obesity
      Prevention Grant Program. Final rule.
AB  - This rule adopts the interim rule implementing the Supplemental Nutrition
      Assistance Program (SNAP) nutrition education and obesity prevention grant
      program with changes as provided in this rule. This rule also amends SNAP
      regulations to implement section 28 of the Food and Nutrition Act (FNA) of 2008,
      as added by section 241 of the Healthy, Hunger-Free Kids Act (HHFKA) of 2010, to
      award grants to States for provision of nutrition education and obesity
      prevention programs. These programs provide services for eligible individuals
      that promote healthy food choices consistent with the current Dietary Guidelines
      for Americans (DGAs). The rule provides State agencies with requirements for
      implementing section 28, including the grant award process and describes the
      process for allocating the Federal grant funding for each State's approved SNAP
      Ed plan authorized under the FNA to carry out nutrition education and obesity
      prevention services each fiscal year. This final rule also implements section
      4028 of the Agricultural Act of 2014 (Farm Bill of 2014), which authorizes
      physical activity promotion in addition to promotion of healthy food choices as
      part of this nutrition education and obesity prevention program.

PMID- 27039410
TI  - Polio vaccines: WHO position paper - March, 2016.

PMID- 27039411
TI  - A journey through 90 years of the Weekly Epidemiological Record.

PMID- 27039413
TI  - Know the four cardiovascular symptoms you should never ignore....

PMID- 27039412
TI  - Message from the World Organisation for Animal Health.

PMID- 27039414
TI  - Into the future: are we ready to face modern outbreaks?

PMID- 27039415
TI  - Study finds warning signs may predict sudden cardiac arrest...

PMID- 27039416
TI  - Study says daily PrEP use is as safe as aspirin.

PMID- 27039417
TI  - Transmission.  Young MSM with detectable HIV more likely to engage in risky sex.

PMID- 27039418
TI  - Why conquering stress can help your heart...

PMID- 27039419
TI  - Happiness may not extend life.

PMID- 27039420
TI  - Bright light helps depression.

PMID- 27039421
TI  - Walnuts can lower cholesterol.

PMID- 27039422
TI  - Stand more to lower your risk of obesity.

PMID- 27039423
TI  - Higher cardio fitness may improve multitasking skills.

PMID- 27039424
TI  - Stronger hands linked to healthier heart.

PMID- 27039425
TI  - Eating more fruit may help lower blood pressure.

PMID- 27039426
TI  - Antidote for blood thinner's side effect.

PMID- 27039427
TI  - Don't ignore signs of sudden cardiac arrest.

PMID- 27039429
TI  - Acupuncture and Alexander technique help relieve chronic neck pain.

PMID- 27039428
TI  - Heart attack survivors can have sex without fear.

PMID- 27039430
TI  - Step up to better heart health.

PMID- 27039431
TI  - Peer support good for the heart.

PMID- 27039433
TI  - Understand the realities of having a bioprosthetic valve...

PMID- 27039432
TI  - Be smart about exercise if you have or are at risk of having heart failure...

PMID- 27039434
TI  - Prostate cancer rates decreasing as screening declines.  Some experts question
      the wisdom of reduced screening.

PMID- 27039435
TI  - Rheumatoid arthritis: treatment options when a biologic agent fails.  Switching
      the type of drug administered can be a game-changer.

PMID- 27039436
TI  - Does dietary fat matter for long-term weight loss?

PMID- 27039437
TI  - Generics vs. brand-name drugs?  Go for generics, doctors' group urges.

PMID- 27039438
TI  - [The physician in the future: physician enhancement?].

PMID- 27039439
TI  - [Toward the lived experience of the physician].
AB  - For manyyears, a major focus of interest has been the patient, in the context of
      a constantly changing society and increasingly complex medical practices. We
      propose to shift this focus on the physician, who is entangled in a similar, but
      less evident way. In these three articles, we explore, in succession, the lived
      experience of the contemporary physician, the ethos which brings together the
      medical community, and the education of the future physician, using research
      projects currently under way within the Service of Liaison Psychiatry at Lausanne
      University Hospital. In this first article, we particularly raise the question of
      what is the lived experience of the physician and sketch the outline of
      <<physician-centered>> research.

PMID- 27039440
TI  - [Three aspects of the medical ethos].
AB  - For many years, a major focus of interest has been the patient, in the context of
      a constantly changing society and increasingly complex medical practices. We
      propose to shift this focus on the physician, who is entangled in a similar, but
      less evident way. In these three articles, we explore, in succession, the lived
      experience of the contemporary physician, the ethos which brings together the
      medical community, and the education of the future physician, using research
      projects currently under way within the Service of Liaison Psychiatry at Lausanne
      University Hospital. Here, we describe three aspects of the medical ethos shaping
      medicine and the physicians: pragmatism, scientific rationality, and the
      individualistic embodiment of clinical practice.

PMID- 27039441
TI  - [Medical education: between science and Bildungsroman].
AB  - For many years, a major focus of interest has been the patient, in the context of
      a constantly changing society and increasingly complex medical practices. We
      propose to shift this focus on the physician, who is entangled in a similar, but
      less evident way. In these three articles, we explore, in succession, the lived
      experience of the contemporary physician, the ethos which brings together the
      medical community, and the education of the future physician, using research
      projects currently under way within the Service of Liaison Psychiatry at Lausanne
      University Hospital. The article hereunder is dedicated to the education and will
      examine the multiple and paradoxical expectations that punctuate it.

PMID- 27039442
TI  - [Illness perceptions: what useful approach to the clinician?].
AB  - The model of illness perceptions presented in this article is exploring how a
      patient perceives the illness. This approach is based upon the idea that
      individuals are constructing representations and knowledge in response to a
      critical event or a threat and building coping strategies and psychological
      adjustment. Inspired from a new paradigm in psychosomatic issued from Heath
      psychology, this approach can be useful to clinician by providing a framework for
      patients to make sense of their illness.

PMID- 27039443
TI  - [Personality and psychophysiologic disorders: risk or opportunity?].

PMID- 27039444
TI  - [Burning mouth syndrome - a joint biopsychosocial approach].
AB  - Burning mouth syndrome (BMS) is a medical condition that is often refractory to
      conventional diagnostic and therapeutic methods. Patients suffering from BMS can
      benefit from a biopsychosocial approach in a joint, medical-psychological
      consultation model. Such a consultation exists at Geneva University Hospitals,
      involving the collaboration of the maxillo-facial and oral surgery division and
      the division of liaison psychiatry and crisis intervention, in order to take into
      account the multiple factors involved in BMS onset and persistence. This article
      will describe BMS clinical presentation, and present an integrate approach to
      treat these patients.

PMID- 27039445
TI  - [Cardiopulmonary resuscitation: the essential of 2015 guidelines].
AB  - Cardiopulmonary resuscitation (CPR) guidelines have been updated in October 2015.
      The 2010 guidelines are reaffirmed: immediate call for help via the local
      dispatch center, high quality CPR (frequency between 100 and 120/min, compression
      depth between 5 and 6 cm) and early defibrillation improve patient's survival
      chances. This article reviews the essential elements of resuscitation and
      recommended advanced measures.

PMID- 27039446
TI  - [Pyoderma gangrenosum, an etiology of chronic ulcer disregarded?].
AB  - We report the case of a 65years old patient followed for more than 4 years for a
      leg ulcer in whom a rare combination of pyoderma gangrenosum with breast cancer
      was diagnosed. This is a rare skin disease, usually associated with systemic
      disease: digestive, rheumatological or malignant. The diagnosis is mainly
      clinical. Taking patient diagnostic management has two objectives: to eliminate
      other causes of skin ulcer and determine whether there is a concomitant illness
      that can be treated. Bacteriological swab and a biopsy should always be
      performed. The treatment consists of topical corticosteroids and systemic therapy
      with corticosteroids or immunosuppressive agents.

PMID- 27039447
TI  - [ZIKA: A PHYSIOPATHOLOGICAL AND EPIDEMIOLOGICAL EQUATION WITH MULTIPLE UNKNOWN
      FACTORS ].

PMID- 27039448
TI  - [FRIENDS FACING DEATH- IN THIS SITUATION OR ELSEWHERE, THERE IS NO GOOD ANSWER
      BUT MULTIPLE CHOICES AND PATHS].

PMID- 27039449
TI  - [MISCELLANEOUS NEWS IN ALCOHOLISM, SCIENCE AND LITERATURE].

PMID- 27039451
TI  - [" HIDE THOSE SMOKERS WHOSE SIGHT OFFENDS US ". TOBACCO, WORLD HEALTH
      ORGANIZATION AND CINEMA].

PMID- 27039450
TI  - [Not Available].

PMID- 27039452
TI  - [Slow rebirth of the idea of moratorium].

PMID- 27039453
TI  - [High Council in Geneva opens a gap in medical secrecy].

PMID- 27039454
TI  - [Boredom, heart of the time].

PMID- 27039455
TI  - [Respiratory tract infections in childhood: what's our status in 2016?].

PMID- 27039456
TI  - [Antibiotics to treat streptococcal pharyngitis in Swiss children: is it still
      useful?].
AB  - Group A Streptococcus (GAS) pharyngitis is a common pediatric infectious disease
      in school-aged children. After the detection of the bacteria in the pharynx,
      treatment with 10 days of antibiotics is recommended in Switzerland. The
      rationale to treat is based on studies from the 1950s, when the epidemiology of
      GAS strain was very different and the incidence of acute rheumatic fever
      significantly higher than today in developed countries. This article explores the
      current national recommendations, as well as the benefits of antibiotic treatment
      in the management of this infection. A reevaluation, as in other countries, of
      the management and treatment of GAS pharyngitis in Switzerland is considered.

PMID- 27039457
TI  - [Acute otitis media and short-term complications].
AB  - Oral antibiotic have changed the incidence of otitic intracranial complications.
      In spite of therapeutic progress, these complications remain serious, potentially
      life-threatening and may result in long-life consequences. Acute otitis media
      diagnosis and knowledge of intracranial complications' symptoms are required for
      early and adapted therapeutics. Care strategies evolve with the continuously
      improvement of medical technologies, development of new vaccines and targeted use
      of antibiotics.

PMID- 27039458
TI  - [Community acquired pneumonia in children: an update for outpatients management].
AB  - Pneumonia should be considered in febrile children with tachypnea and/or chest
      recession. Virus are the most common cause of pneumonia in children under 5 years
      old. Streptococcus pneumonia can be found at any age. Mycoplasma pneumonia is
      more frequent in older children. Systematic chest radiograph is not necessary but
      must be obtained in patients with hypoventilation and in those with failed
      initial antibiotic therapy. Mycoplasma pneumonia should be tested according to
      patient age and response to initial antibiotic. First line antibiotherapy is
      amoxicilline. Antibiotic treatment is frequently not necessary in children under
      5 but should be considered depending on clinical presentation and C reactive
      protein value.

PMID- 27039459
TI  - [Impact of vaccination on acute otitis media].
AB  - Acute otitis media (AOM) is an important reason for medical visits and antibiotic
      use in children, with possible complications. Pneumococcal conjugate vaccines
      (PCV) have been developed from 2000, with first the apparition of the 7-valent
      PCV (PCV7), and from 2013, of the 13-valent PCV (PCV13). First developed to
      prevent invasive pneumococcal infections, they have been shown to reduce the
      number of AOM as well. PC13 has allowed to reduce the nasopharyngeal carriage of
      the majority of pneumococcal serotypes found in AOM, with a reduction of 77% of
      pneumococcal AOM, according to one study.

PMID- 27039460
TI  - [Impact of vaccination on the epidemiology of childhood pneumonia].
AB  - The impact of vaccination on non-bacteremic Haemophilus influenza pneumonia is
      difficult to appreciate, in the absence of proper microbiological documentation.
      It has certainly been largely underestimated. Vaccination has reduced the
      incidence of pneumococcal pneumonia. However, the increase of incidence of
      empyema due to nonvaccine serotypes was observed in several countries. The
      replacement of Prevenar 7 by Prevenar 13 portends a decrease in the occurrence of
      these infections, but, unfortunately, without eliminating them completely.

PMID- 27039461
TI  - [Respiratory viruses in pediatrics: what's new?].
AB  - Molecular diagnostic tests have greatly increased our knowledge regarding the
      contribution of respiratory viruses in respiratory illnesses in children, mainly
      lower respiratory tract infections. Respiratory syncytial virus, rhinovirus (RV)
      and human metapneumovirus (hMPV) are predominant viral agents identified in
      children. Notwithstanding the importance of respiratory viruses in children,
      treatment and prophylactic options remain limited. These include palivizumab, a
      monoclonal antibody prophylactically administred to high risk children against
      RSV, vaccines and antivirals such as oseltamivir targeting influenza viruses.

PMID- 27039462
TI  - [Clinical scores for the risk of recurrent VTED and for the relationship cancer
      VTED].
AB  - Clinical scores related to the risk of recurrent venous thromboembolic disease
      (VTED), to the relationship between cancer and VTED (risk of development of VTED,
      risk of recurrent VTED, prognosis of pulmonary embolism) and to the risk of
      cancer following VTED are analysed and commented upon. Although they most often
      rely on appropriate methodology and are often based on a large number of
      subjects, they unfortunately provide information that is not necessarily useful
      for the care of patients. Their use should be considered only when positive
      impact studies are published.

PMID- 27039463
TI  - [Tara's house, live until the end, feeling at home].

PMID- 27039464
TI  - [FRENCH BIO-PIRATES AND QUASSIA AMARA HERBAL PREPARATION AGAINST MALARIA. ].

PMID- 27039465
TI  - [TOMORROW?].

PMID- 27039466
TI  - [Is light therapy useful in summer too?].

PMID- 27039467
TI  - [THE LONG ROAD TOWARDS ANTI-SUICIDE DRUG TREATMENT].

PMID- 27039468
TI  - [REPRODUCTION AND CRYOPRESERVATION: WORDS FROM ZYGOTE'S WORLD].

PMID- 27039469
TI  - [Federal council is mobilizing 100 millions of Francs to educate more
      physicians].

PMID- 27039470
TI  - [In Switzerland, the problem is not a shortage of physicians but rather their
      specialties].

PMID- 27039471
TI  - [New England Journal of Medicine catalyst: and the critical brain?].

PMID- 27039472
TI  - Low Energy Surface Activation of Zirconia Based Restorations.
AB  - PURPOSE: To evaluate the influence of low energy surface activation technique on
      the biaxial flexure strength of zirconia frameworks. MATERIALS AND METHODS:
      Zirconia discs were prepared by cutting CAD/CAM zirconia blocks. Sintered discs
      were airborne particle abraded using one of the following particles: 30 MUm
      alumina particles, 50 MUm alumina particles, or modified round edges 30 MUm
      alumina particles at low pressure. Scanning electron microscopy, x-ray
      diffraction analysis, surface roughness, and biaxial flexure strength tests were
      performed (n = 20). Fractured specimens were fractographically analyzed (alpha =
      0.05). RESULTS: Low energy surface activation resulted in 7% monoclinic
      crystallographic transformation, increasing surface roughness from 0.05 to 0.3
      MUm and in significant increase in biaxial flexure strength (1718 MPa) compared
      30 MUm (1064 MPa), 50 MUm (1210 MPa), and as-sintered specimens (1150 MPa).
      CONCLUSIONS: Low energy surface activation of zirconia specimens improved the
      biaxial flexure strength of zirconia frameworks without creation of surface
      damage. Clinical implications: by controlling particle size and shape of alumina,
      the flexure strength of zirconia restorations could be increased usinglow
      pressure particle abrasion.

PMID- 27039473
TI  - The Accuracy of Fit of Crowns Made From Wax Patterns Produced Conventionally
      (Hand Formed) and Via CAD/CAM Technology.
AB  - OBJECTIVE: The aim of this study was to compare the marginal and internal fit
      accuracy of crowns constructed using three different wax production methods;
      conventional, milled, and 3D printed and utilizing three different cement gap
      thicknesses. METHODS: 15 identical stone dies were made for each method. Wax
      patterns were produced and then cast into metal crowns, which were assessed for
      differences in accuracy of both marginal and internal fit. Measurement points
      were 4 points per crown; occlusal, axial, marginal gap, and marginal discrepancy
      points. A silicone impression technique and conventional cementation technique
      were employed to facilitate the measurements. RESULTS: There was no significant
      difference (p > 0.05) in accuracy between the digitally and manually produced
      crowns, with the 3D printed crowns being slightly more accurate. Whereas,
      statistically significant differences were noticed between the conventional
      versus printed groups, in occlusal and marginal gap points (p < 0.05).
      CONCLUSION: The marginal and internal fit of 3D printed wax patterns is more
      accurate than the other two production methods. The milling of wax crowns is as
      accurate as the conventional hand carved production in terms of internal and
      marginal fit. The manufacturer recommended offset/die-spacer of 30 MUm produced
      the most accurate internal and marginal fits.

PMID- 27039474
TI  - Impact of Referral Protocols on the Dental Management of Patients Undergoing
      Treatment for Head and Neck Oncology in Northern Ireland.
AB  - Management of head and neck oncology necessitates an extensive multidisciplinary
      approach. Throughout Northern Ireland all oral care for Head and Neck Oncology
      patients is overseen within the Centre for Dentistry, Queens University Belfast
      via referral from the Head and Neck Multidisciplinary Team. The aim of this study
      was to develop and introduce a referral pro-forma to improve communication
      between members of the multidisciplinary team and ultimately expedite provision
      of oral care prior to patients undergoing treatment for Head and Neck Oncology.
      The study period ran from June 2013 until November 2014. All patients undergoing
      treatment for Head and Neck Oncology in Northern Ireland were included in the
      study. A referral pro-forma was introduced in June 2014 in an attempt to
      streamline the referral process. Data was gathered on patient waiting times,
      extraction protocols with comparisons made between the period before and after
      introduction of the pro-forma. In total 137 patients were included in the study:
      96 patients were referred to the service using referral letters, confidential
      emails and via telephone; 41 patients were referred using the pro-forma. The
      introduction of the referral pro-forma resulted in a significant decrease in the
      mean number of days from referral to assessment (12 to 7 days) (p < 0.05) and
      significantly increased mean interval time between extractions and patients
      beginning radiotherapy (13 to 17 days) (p < 0.05). Significant improvements have
      been made with the introduction of the referral pro-forma where patients are
      waiting significantly less time for dental assessment and having extractions
      completed in a more timely manner therefore expediting the commencement of their
      oncology treatment.

PMID- 27039475
TI  - Zirconia Abutment Supporting All Ceramic Crowns in the Esthetic Zone: Interim
      Results of a Prospective Study.
AB  - AIM: This prospective study evaluated peri-implant tissues around all-ceramic
      crowns fabricated using CAD/CAM technology. MATERIAL AND METHODS: Twenty-five
      patients received pre-fabricated zirconia implant abutments with CAD/CAM zirconia
      copings in the esthetic zone. Implants were evaluated at baseline, and at 3 and 6
      months in function. RESULTS: Radiographic analyzes showed stable bone crest
      around the implants. Esthetics were more favorable as time lapsed (p > 0.05).
      Bleeding Index was constant in all time intervals. Plaque index reduced from 3 to
      6 months. CONCLUSION: The all-ceramic CAD/CAM crowns were clinically,
      radiographically and esthetically stable during the study period.

PMID- 27039476
TI  - Prosthetic Complications and Maintenance Requirements in Locator-attached Implant
      Supported Overdentures: A Retrospective Study.
AB  - Retrospective data of 32 patients supplied with implant-supported and Locator
      attached overdentures were screened for prosthetic complications and maintenance
      requirements, which were recorded and statistically analyzed. Mean observation
      time was 4.78 +/- 1.72) years. Loss of retention was the most frequently observed
      event (n = 22). Damage and exchange of the insert holders (n = 4) and loosening
      of locator attachments (n = 2) and fracture of the insert holder (n = 2) were
      uncommon events; no loss of locator attachments was observed. Loss of retention
      in Locator-attached overdentures is frequent; correlating patient-specific
      parameters with prosthetic complications is necessary to define recommendations
      for the use of Locator attachments.

PMID- 27039477
TI  - Prosthodontic Rehabilitation for a Patient with Ellis-Van Creveld Syndrome: A
      Case Report.
AB  - Patients suffering from Ellis-Van-Creveld syndrome are a challenge for dental
      management. Aesthetics are a major concern with limited manual dexterity, making
      choice of treatment critical. A 38 year old female diagnosed with Ellis-Van
      Creveld syndrome presented with stained teeth and un-aesthetic smile and related
      that to her low self-esteem and depression. Intra-oral examination revealed mal
      aligned megadont central incisors in the maxillary arch, fused mandibular canines
      with laterals and missing central incisors with space discrepancy and pronounced
      reverse over jet and overbite. Treatment involved non-surgical periodontal
      management, fabrication of veneers and dentine bonded crowns for maxillary
      anteriors and fixed-fixed resin retained bridge for mandibular arch.

PMID- 27039478
TI  - Implant Treatment in Patients with Sjogren's Syndrome: A Review of the Literature
      and Two Clinical Case Reports.
AB  - Implant rehabilitation in patients with Sjogren's Syndrome is reported to offer
      an improvementin the quality of life, but the scientific evidence on implant
      survival in patients with Sjogren's Syndrome is scarce. The paper presents a
      review of the literature on the performance of dental implants in patients with
      Sjogren's Syndrome and two case reports of patients with Sjogren's Syndrome
      treated successfully with dental implants. Two female patients suffering from
      Sjogren's Syndrome were rehabilitated with implant-supported prostheses. After
      eighteen months and two years respectively, the patients were satisfied with
      function and aesthetics; restorations were comfortable, stable radiographic bone
      levels were noted and xerostomia was not reported to affect the function anymore.

PMID- 27039479
TI  - Making "Someday" Happen- The Years of Living Dangerously.

PMID- 27039480
TI  - The Hospital as a Factory and the Physician as an Assembly Line Worker.

PMID- 27039481
TI  - Sustainable Growth Rate Repeal: Why the "Why" Matters.

PMID- 27039482
TI  - Growing the Life Sciences in Missouri & Kansas into A Global Epicenter--Path to
      2025.

PMID- 27039483
TI  - Implementing Change to Reduce Depression, Suicide, and Burnout Among Physicians
      in-Training.

PMID- 27039484
TI  - Protecting Against Tax ID Theft and Avoiding Other Fraudulent Tax Schemes.

PMID- 27039485
TI  - A Call for Fairness in Drug Prices.

PMID- 27039486
TI  - Greene County Medical Society on the Move.

PMID- 27039487
TI  - MU School of Medicine: Understanding the Importance of Inclusion, Diversity, and
      Civility in Education.

PMID- 27039488
TI  - MU Ophthalmology Charts a Future of Growth.

PMID- 27039489
TI  - Visual Acuity Outcomes of Toric Lens Implantation in Patients Undergoing Cataract
      Surgery at a Residency Training Program.
AB  - Ophthalmology residents must become competent in the use of a variety of
      intraocular lenses (IOLs) and refractive technologies designed to reduce
      spectacle use after cataract surgery. Our study of visual acuity outcomes with
      toric IOLs at the Harry S. Truman Memorial Veterans' Hospital revealed that
      residents achieved an uncorrected visual acuity of 20/40 or better in 88% of the
      surgeries they performed, a rate comparable to that reported by other residency
      programs and by cataract surgeons.

PMID- 27039490
TI  - Vitrectomy as a Risk Factor for Complicated Cataract Surgery.
AB  - A retrospective review of 98 cases of complicated cataract surgery and/or delayed
      intraocular lens (IOL) dislocation examined the relationship between vitrectomy
      and cataract surgery complications. Nine (9.2%) of the 98 patients had a history
      of vitrectomy, before or after cataract surgery, and each had complicated
      cataract surgery. Six patients who underwent vitrectomy before cataract surgery
      experienced intraoperative complications. Three patients in whom vitrectomy was
      performed after uneventful cataract surgery subsequently had delayed IOL
      dislocation.

PMID- 27039491
TI  - Vaccine-Associated Uveitis.
AB  - All of the widely administered vaccines have been reported to cause uveitis. The
      ocular inflammation is usually temporary and resolves with topical ocular
      steroids. During a 26-year period, a total of 289 cases of vaccine-associated
      uveitis were reported to three adverse reaction reporting databases. Hepatitis B
      vaccine, either alone or administered with other vaccines, appears to be the
      leading offender. Clinicians are encouraged to report cases of vaccine- or drug
      associated ocular adverse reactions to www.eyedrugregistry.com.

PMID- 27039492
TI  - Central Retinal Artery Occlusion: A Literature Review and the Rationale for
      Hyperbaric Oxygen Therapy.
AB  - Central retinal artery occlusion is visually devastating and has no proven
      treatments. The therapeutic interval between symptom onset and potentially sight
      saving intervention is narrow. Traditional conservative approaches include
      digital massage, administration of systemic vasodilators and diuretics, and
      lowering of intraocular pressure. Systemic and targeted fibrinolytic therapy is
      under investigation but is associated with significant adverse reactions. We
      report a case in which hyperbaric oxygen therapy restored retinal perfusion, and
      the patient's vision was improved.

PMID- 27039493
TI  - The Evolution of Cataract Surgery.
AB  - Cataract surgery is one of the most common procedures performed worldwide. It is
      also one of the oldest. Alongside advancements in cataract surgical techniques
      have been improvements in intraocular lens replacement technology. Cataract
      surgery may be considered among the most successful treatments in all of
      medicine. This article discusses the fascinating evolution of cataract surgery,
      from the earliest approach of couching to modern day phacoemulsification and lens
      replacement.

PMID- 27039494
TI  - Diagnostic Considerations in Patients Presenting with Transient Vision Loss.
AB  - A complete history is essential for determining whether the underlying etiology
      of transient vision loss is from an ischemic or a nonischemic condition that
      originates in the eye or elsewhere. Ischemic transient vision loss constitutes a
      transient ischemic attack and requires a full work-up for ischemic stroke. If
      carotid artery stenosis is found, early intervention may improve the clinical
      outcome. This article highlights the diagnostic considerations in the evaluation
      of patients with transient vision loss.

PMID- 27039495
TI  - Turn on the Music: Cochlear Implants.

PMID- 27039496
TI  - Is It Painful to Manage Chronic Pain? A Cross-Sectional Study of Physicians In
      Training in a University Program.
AB  - BACKGROUND: Prescribing opioids for chronic non-cancer pain (CNCP) is a challenge
      due to associated risks from abuse, addiction and adverse effects. We surveyed
      resident physicians on their knowledge, attitude and practices in opioid
      prescription practices in the ambulatory setting and conducted an educational
      module to address their knowledge gaps. METHODS: A phase 1 survey assessed
      knowledge, attitudes and practices of residents in the out-patient management of
      CNCP with opioids. Demographics, numbers of patients seen, those with concerns
      for risky behaviors, adverse effects and the reasons for concern were also
      recorded. In Phase 2, an educational module in the form of didactics and case
      based discussions addressed the perceived deficiencies noted from results of
      phase 1 survey. Pre and post module surveys assessed the effectiveness of the
      educational module. RESULTS: In the phase 1 study (45/49, 92% response rate, M:F
      = 30:15) 33.3% (15/45) were in Post-Graduate Year (PGY) 1, 35.6% (16/45) PGY2s
      and 31.1% (14/45) PGY3s; 80% (36/45) saw more than one patient with CNCP in the
      previous 3 months; 62.2% (28/45) had at least one patient with concerns for
      misuse and addiction; 77.8% (35/45) and 86.7% (39/45) reported a lack of training
      and consistent documentation respectively, and 82.2% (37/45) were uncomfortable
      to refill for other provider's patients. All (100%, 45/45) consulted the clinical
      pharmacist; 86.7% (39/45) believed that either focused education would be
      beneficial. In the phase 2 study (44/49, 89.7% response rate, M: F = 29: 15), the
      pre- and post-module responses showed that > 90% of the residents perceived
      improvement in knowledge and confidence in management of CNCP with opioids after
      the educational module. CONCLUSIONS: Internal medicine residents perceived
      deficits in their ability to manage CNCP. Following a focused educational
      training, residents' knowledge and confidence in prescription of opioids
      improved, demonstrating the need to include management of CNCP with opioids into
      their curriculum.

PMID- 27039497
TI  - Hospital Personnel Attitude Toward Utilization of Depth Imaging Technology in
      Hospital Rooms.
AB  - Research supports that the use of alarm intervention technology alone does not
      conclusively reduce fall incidents. In an effort to address the need for broader
      use of intervention technology, a study was conducted at a large Missouri
      hospital. The purpose of the study was to determine hospital personnel
      perceptions toward the utilization of depth imaging technology in hospital rooms
      and to explore expanded use of video surveillance systems in the patient room.

PMID- 27039498
TI  - Act 1232 of 2015--Improving the Credentialing Process.

PMID- 27039499
TI  - Chronic Disease Management & Long-Term Relationship.

PMID- 27039500
TI  - Arkansas Trauma System & Related Measures Saving Lives, Improving Stats.

PMID- 27039501
TI  - Medicaid Meaningful Use Incentives.

PMID- 27039502
TI  - Managing Pulmonary Complications in Children with Neurodisabilities.
AB  - The pulmonary service at ACH is available 24 hours a day for the primary care
      physician who has the potential to be an important member of the team caring for
      these children. Initial evaluation and management utilizing the concepts
      presented in this article may allow the acute illness to be handled at home
      without the need for referral to ACH. When that is accomplished, not only does
      the child benefit but the entire family benefits by not having the total
      disruption that occurs with emergent trips to ACH and especially when
      hospitalization ensues. In this way the primary care physician provides a very
      important service not only to the sick child but also to the entire family unit.
      Thus the role of the primary care physician takes on special significance in the
      overall management of the patient.

PMID- 27039503
TI  - Sister Mary Joseph Nodule: A Case Report and Review.

PMID- 27039504
TI  - Absurdities From the Wrong Side of the Sheets. Part 1--Becoming A Patient.

PMID- 27039505
TI  - Protected areas and their surrounding territory: socioecological systems in the
      context of ecological solidarity.
AB  - The concept of ecological solidarity (ES) is a major feature of the 2006 law
      reforming national park policy in France. In the context of biodiversity
      conservation, the objectives of this study are to outline the historical
      development of ES, provide a working definition, and present a method for its
      implementation that combines environmental pragmatism and adaptive management.
      First, we highlight how ES provides a focus on the interdependencies among humans
      and nonhuman components of the socioecological system. In doing so, we identify
      ES within a framework that distinguishes ecological, socioecological, and
      sociopolitical interdependencies. In making such interdependencies apparent to
      humans who are not aware of their existence, the concept of ES promotes
      collective action as an alternative or complementary approach to state- or market
      based approaches. By focusing on the awareness, feelings, and acknowledgement of
      interdependencies between actors and between humans and nonhumans, we present and
      discuss a learning-based approach (participatory modeling) that allows
      stakeholders to work together to construct cultural landscapes for present and
      future generations. Using two case studies, we show how an ES analysis goes
      beyond the ecosystem management approach to take into account how human
      interactions with the environment embody cultural, social, and economic values
      and endorse an ethically integrated science of care and responsibility. ES
      recognizes the diversity of these values as a practical foundation for socially
      engaged and accountable actions. Finally, we discuss how ES enhances academic
      support for a socioecological systems approach to biodiversity conservation and
      promotes collaboration with decision-makers and stakeholders involved in the
      adaptive management of protected areas and their surrounding landscapes.

PMID- 27039506
TI  - Multiyear drought-induced morbidity preceding tree death in southeastern U.S.
      forests.
AB  - Recent forest diebacks, combined with threats of future drought, focus attention
      on the extent to which tree death is caused by catastrophic events as opposed to
      chronic declines in health that accumulate over years. While recent attention has
      focused on large-scale diebacks, there is concern that increasing drought stress
      and chronic morbidity may have pervasive impacts on forest composition in many
      regions. Here we use long-term, whole-stand inventory data from southeastern U.S.
      forests to show that trees exposed to drought experience multiyear declines in
      growth prior to mortality. Following a severe, multiyear drought, 72% of trees
      that did not recover their pre-drought growth rates died within 10 yr. This
      pattern was mediated by local moisture availability. As an index of morbidity
      prior to death, we calculated the difference in cumulative growth after drought
      relative to surviving conspecifics. The strength of drought-induced morbidity
      varied among species and was correlated with drought tolerance. These findings
      support the ability of trees to avoid death during drought events but indicate
      shifts that could occur over decades. Tree mortality following drought is
      predictable in these ecosystems based on growth declines, highlighting an
      opportunity to address multiyear drought-induced morbidity in models,
      experiments, and management decisions.

PMID- 27039507
TI  - Decadal Bering Sea seascape change: consequences for Pacific walruses and
      indigenous hunters.
AB  - The most significant factors currently affecting the Pacific walrus (Odobenus
      rosmarus divergens) population are climate change and consequent changes in sea
      ice morphology and dynamics. This paper integrates recent physical sea-ice change
      in the Bering Sea with biological and ecological conditions of walruses in their
      winter-spring reproductive habitat. Historically, walrus in winter-spring
      depended on a critical mass of sea-ice habitat to optimize social networking,
      reproductive fitness, feeding behavior, migration, and energetic efficiency.
      During 2003-2013, our cross-disciplinary, multiscale analysis from shipboard
      observations, satellite imagery, and ice-floe tracking, reinforced by information
      from indigenous subsistence hunters, documented change of sea-ice structure from
      a plastic continuum to a "mixing bowl" of ice floes moving more independently.
      This fragmentation of winter habitat preconditions the walrus population toward
      dispersal mortality and will also negatively affect the availability of resources
      for indigenous communities. We urge an expanded research and management agenda
      that integrates walrus natural history and habitat more completely with changing
      sea-ice morphology and dynamics at multiple scales, while also meeting the needs
      of local communities.

PMID- 27039508
TI  - Alternative scenarios of bioenergy crop production in an agricultural landscape
      and implications for bird communities.
AB  - Increased demand and government mandates for bioenergy crops in the United States
      could require a large allocation of agricultural land to bioenergy feedstock
      production and substantially alter current landscape patterns. Incorporating
      bioenergy landscape design into land-use decision making could help maximize
      benefits and minimize trade-offs among alternative land uses. We developed
      spatially explicit landscape scenarios of increased bioenergy crop production in
      an 80-km radius agricultural landscape centered on a potential biomass-processing
      energy facility and evaluated the consequences of each scenario for bird
      communities. Our scenarios included conversion of existing annual row crops to
      perennial bioenergy grasslands and conversion of existing grasslands to annual
      bioenergy row crops. The scenarios explored combinations of four biomass crop
      types (three potential grassland crops along a gradient of plant diversity and
      one annual row crop [corn]), three land conversion percentages to bioenergy crops
      (10%, 20%, or 30% of row crops or grasslands), and three spatial configurations
      of biomass crop fields (random, clustered near similar field types, or centered
      on the processing plant), yielding 36 scenarios. For each scenario, we predicted
      the impact on four bird community metrics: species richness, total bird density,
      species of greatest conservation need (SGCN) density, and SGCN hotspots (SGCN
      birds/ha >= 2). Bird community metrics consistently increased with conversion of
      row crops to bioenergy grasslands and consistently decreased with conversion of
      grasslands to bioenergy row crops. Spatial arrangement of bioenergy fields had
      strong effects on the bird community and in some cases was more influential than
      the amount converted to bioenergy crops. Clustering grasslands had a stronger
      positive influence on the bird community than locating grasslands near the
      central plant or at random. Expansion of bioenergy grasslands onto marginal
      agricultural lands will likely benefit grassland bird populations, and bioenergy
      landscapes could be designed to maximize biodiversity benefits while meeting
      targets for biomass production.

PMID- 27039509
TI  - Hemiparasite--host plant interactions in a fragmented landscape assessed via
      imaging spectroscopy and LiDAR.
AB  - Species interactions are susceptible to anthropogenic changes in ecosystems, but
      this has been poorly investigated in a spatially explicit manner in the case of
      plant parasitism, such as the omnipresent hemiparasitic mistletoe-host plant
      interactions. Analyzing such interactions at a large spatial scale may advance
      our understanding of parasitism patterns over complex landscapes. Combining high
      resolution airborne imaging spectroscopy and LiDAR, we studied hemiparasite
      incidence within and among tree host stands to examine the prevalence and spatial
      distribution of hemiparasite load in ecosystems. Specifically, we aimed to
      assess: (1) detection accuracy of mistletoes on their oak hosts; (2)
      hemiparasitism prevalence within host tree canopies depending on tree height, and
      (3) spatial variation in hemiparasitism across fragmented woodlands, in a low
      diversity mediterranean oak woodland in California, USA. We identified mistletoe
      infestations with 55-96% accuracy, and detected significant differences in remote
      sensed spectra between oak trees with and without mistletoe infestation. We also
      found that host canopy height had little influence on infestation degree, whereas
      landscape-level variation showed consistent; non-random patterns: isolated host
      trees had twice the infestation load than did trees located at the core of forest
      fragments. Overall, we found that canopy exposure (i.e., lower canopy density or
      proximity to forest edge) is more important than canopy height for mistletoe
      infestation, and that by changing landscape structure, parasitic prevalence
      increased with woodland fragmentation. We conclude that reducing fragmentation in
      oak woodlands will minimize anthropogenic impact on mistletoe infestation at the
      landscape level. We argue that advanced remote sensing technology can provide
      baselines to quantitatively analyze and monitor parasite-host trajectories in
      light of global environmental change, and that this is a promising approach to be
      further tested in other temperate and tropical forests.

PMID- 27039510
TI  - Gene--environment interactions influence feeding and anti-predator behavior in
      wild and transgenic coho salmon.
AB  - Environmental conditions are known to affect phenotypic development in many
      organisms, making the characteristics of an animal reared under one set of
      conditions not always representative of animals reared under a different set of
      conditions. Previous results show that such plasticity can also affect the
      phenotypes and ecological interactions of different genotypes, including animals
      anthropogenically generated by genetic modification. To understand how plastic
      development can affect behavior in animals of different genotypes, we examined
      the feeding and risk-taking behavior in growth-enhanced transgenic coho salmon
      (with two- to threefold enhanced daily growth rates compared to wild type) under
      a range of conditions. When compared to wild-type siblings, we found clear
      effects of the rearing environment on feeding and risk-taking in transgenic
      animals and noted that in some cases, this environmental effect was stronger than
      the effects of the genetic modification. Generally, transgenic fish, regardless
      of rearing conditions, behaved similar to wild-type fish reared under natural
      like conditions. Instead, the more unusual phenotype was associated with wild
      type fish reared under hatchery conditions, which possessed an extreme risk
      averse phenotype compared to the same strain reared in naturalized conditions.
      Thus, the relative performance of genotypes from one environment (e.g.,
      laboratory) may not always accurately reflect ecological interactions as would
      occur in a different environment (e.g., nature). Further, when assessing risks of
      genetically modified organisms, it is important to understand how the environment
      affects phenotypic development, which in turn may variably influence consequences
      to ecosystem components across different conditions found in the complexity of
      nature.

PMID- 27039511
TI  - Sperm whales reduce foraging effort during exposure to 1-2 kHz sonar and killer
      whale sounds.
AB  - The time and energetic costs of behavioral responses to incidental and
      experimental sonar exposures, as well as control stimuli, were quantified using
      hidden state analysis of time series of acoustic and movement data recorded by
      tags (DTAG) attached to 12 sperm whales (Physeter macrocephalus) using suction
      cups. Behavioral state transition modeling showed that tagged whales switched to
      a non-foraging, non-resting state during both experimental transmissions of low
      frequency active sonar from an approaching vessel (LFAS; 1-2 kHz, source level
      214 dB re 1 uPa m, four tag records) and playbacks of potential predator (killer
      whale, Orcinus orca) sounds broadcast at naturally occurring sound levels as a
      positive control from a drifting boat (five tag records). Time spent in foraging
      states and the probability of prey capture attempts were reduced during these two
      types of exposures with little change in overall locomotion activity, suggesting
      an effect on energy intake with no immediate compensation. Whales switched to the
      active non-foraging state over received sound pressure levels of 131-165 dB re 1
      uPa during LFAS exposure. In contrast, no changes in foraging behavior were
      detected in response to experimental negative controls (no-sonar ship approach or
      noise control playback) or to experimental medium-frequency active sonar
      exposures (MFAS; 6-7 kHz, source level 199 re 1 uPa m, received sound pressure
      level [SPL] = 73-158 dB re 1 uPa). Similarly, there was no reduction in foraging
      effort for three whales exposed to incidental, unidentified 4.7-5.1 kHz sonar
      signals received at lower levels (SPL = 89-133 dB re 1 uPa). These results
      demonstrate that similar to predation risk, exposure to sonar can affect
      functional behaviors, and indicate that increased perception of risk with higher
      source level or lower frequency may modulate how sperm whales respond to
      anthropogenic sound.

PMID- 27039512
TI  - Ecological equivalency as a tool for endangered species management.
AB  - The use of taxon substitutes for extinct or endangered species is a controversial
      conservation measure. We use the example of the endangered California tiger
      salamander (Ambystoma californiense; CTS), which is being replaced by hybrids
      with the invasive barred tiger salamander (Ambystoma mavortium), to illustrate a
      strategy for evaluating taxon substitutes based on their position in a
      multivariate community space. Approximately one-quarter of CTS's range is
      currently occupied by "full hybrids" with 70% nonnative genes, while another one
      quarter is occupied by "superinvasives" where a specific set of 3/68 genes
      comprising 4% of the surveyed genome is nonnative. Based on previous surveys of
      natural CTS breeding ponds, we stocked experimental mesocosms with field
      verified, realistic densities of tiger salamander larvae and their prey, and used
      these mesocosms to evaluate ecological equivalency between pure CTS, full
      hybrids, and superinvasives in experimental pond communities. We also included a
      fourth treatment with no salamanders present to evaluate the community effects of
      eliminating Ambystoma larvae altogether. We found that pure CTS and superinvasive
      larvae were ecologically equivalent, because their positions in the multivariate
      community space were statistically indistinguishable and they did not differ
      significantly along any univariate community axes. Full hybrids were ecologically
      similar, but not equivalent, to the other two genotypes, and the no-Ambystoma
      treatment was by far the most divergent. We conclude that, at least for the
      larval stage, superinvasives are adequate taxon substitutes for pure CTS and
      should probably be afforded protection under the Endangered Species Act. The
      proper conservation status for full hybrids remains debatable.

PMID- 27039513
TI  - A long-term evaluation of applied nucleation as a strategy to facilitate forest
      restoration.
AB  - Applied nucleation is a restoration technique that seeks to facilitate woody
      plant establishment by attracting birds or other animals that may introduce seeds
      of dispersal-limited species. In 1991, an experimental test of applied nucleation
      was initiated in an abandoned landfill in New Jersey, USA. Trees and shrubs were
      planted into 16 10 x 10 m plots, covering < 3% of the 6-ha site. In 2010-2011, we
      sampled the plant community to test the impact of the treatments on forest cover
      and plant biodiversity. Site-wide forest cover increased substantially in the 19
      years since planting from none to 59%. The original planted plots had
      significantly higher stem density, particularly of bird-dispersed species, than
      unplanted areas. Species composition outside the planted plots was dominated by
      the wind-dispersed Fraxinus americana and several small-seeded bird-dispersed
      species, but there were few species indicative of later successional stages. The
      expected model of successional development via the nucleation model that rates of
      colonization would be highest near plantings and that forest cover would spread
      outward from established clusters was not supported after this time span. Given
      the site's isolation from potential sources of woody propagules, the experimental
      treatments may not have been enough to overcome many species' dispersal
      limitation. Regardless of the mechanism, however, the treatments transformed the
      once essentially treeless site into a densely wooded habitat, and did so at a
      rate faster than other descriptions of reforestation following disturbances or
      land-use changes in the region. Despite the relatively low species richness of
      the community, this experiment demonstrated that reforestation of even severely
      degraded habitat can be achieved with minimal management after site preparation
      and cluster plantings.

PMID- 27039514
TI  - Bird functional diversity decreases with time since disturbance: Does patchy
      prescribed fire enhance ecosystem function?.
AB  - Animal species diversity is often associated with time since disturbance, but the
      effects of disturbances such as fire on functional diversity are unknown.
      Functional diversity measures the range, abundance, and distribution of trait
      values in a community, and links changes in species composition with the
      consequences for ecosystem function. Improved understanding of the relationship
      between time since fire (TSF) and functional diversity is critical given that the
      frequency of both prescribed fire and wildfire is expected to increase. To
      address this knowledge gap, we examined responses of avian functional diversity
      to TSF and two direct measures of environmental heterogeneity, plant diversity,
      and structural heterogeneity. We surveyed birds across a 70-year chronosequence
      spanning four vegetation types in southeast Australia. Six bird functional traits
      were used to derive four functional diversity indices (richness, evenness,
      divergence, and dispersion) and the effects of TSF, plant diversity and
      structural heterogeneity on species richness and the functional diversity indices
      were examined using mixed models. We used a regression tree method to identify
      traits associated with species more common in young vegetation. Functional
      richness and dispersion were negatively associated with TSF in all vegetation
      types, suggesting that recent prescribed fire generates heterogeneous vegetation
      and provides greater opportunities for resource partitioning. Species richness
      was not significantly associated with TSF, and is probably an unreliable
      surrogate for functional diversity in fire-prone systems. A positive,
      relationship between functional evenness and structural heterogeneity was comnon
      to all vegetation types, suggesting that fine-scale (tens of meters) structural
      variation can enhance ecosystem function. Species more common in young vegetation
      were primarily linked by their specialist diets, indicating that ecosystem
      services such as seed dispersal and insect control are enhanced in more recently
      burnt vegetation. We suggest that patchy prescribed fire sustains functional
      diversity, and that controlled use of patchy fire to break up large expanses of
      mature vegetation will enhance ecosystem function.

PMID- 27039515
TI  - Shrubland resilience varies across soil types: implications for operationalizing
      resilience in ecological restoration.
AB  - In ecosystems with alternative stable states, restoration success can be thought
      of as overcoming the resilience of an undesirable state to promote an alternative
      state that yields greater ecosystem services. Since greater resilience of
      undesirable states translates into reduced restoration potential, quantifying
      differences in resilience can enhance restoration planning. In the context of
      shrub-encroached rangeland restoration, shrubland resilience is the capacity of a
      woody vegetated state to absorb management interventions designed to produce a
      more desirable grass-dominated state, and remain within its current regime.
      Therefore, differences in the resilience of a state can be quantified in a
      relative sense by measuring whether a state switches to an alternate state
      following perturbation or remains in its current stability domain. Here we
      designed an experimental manipulation to assess the contribution of soils to
      differences in the relative resilience of a shrub-invaded state. In this large
      scale experiment, we repeated perturbations across a gradient of soil textures to
      inform restoration practitioners of differences in the relative resilience of
      shrubland occurring on different soil types to common rangeland restoration
      practices. On each soil type, we compared the relative ability of the shrubland
      state to withstand chemical and mechanical brush control treatments, commonly
      employed in this study region, to untreated controls. While the shrubland
      community composition did not differ prior to the study, its capacity to absorb
      and recover from brush removal treatments depended on soil type. Shrubland
      resilience to chemical and mechanical brush removal was highest on coarse soils.
      On these soils, brush removal temporarily restored grassland dominance, but woody
      plants quickly regained pretreatment levels of dominance. However, shrublands on
      fine soils did not recover following treatments, continuing to be grass-dominated
      for the duration of the study. This study highlights a simple approach for
      prioritizing restoration actions by mapping the locations of different soil
      attributes that support shrub-dominated states with differing levels of
      resilience to brush control. This experimental approach provides a basis for
      operationalizing resilience in restoration and prioritizing management actions
      across a range of environmental conditions, which is critical given the economic
      constraints associated with broad-scale mechanical and chemical interventions for
      rangeland restoration.

PMID- 27039516
TI  - Trade-offs between three forest ecosystem services across the state of New
      Hampshire, USA: timber, carbon, and albedo.
AB  - Forests are more frequently being managed to store and sequester carbon for the
      purposes of climate change mitigation. Generally, this practice involves long
      term conservation of intact mature forests and/or reductions in the frequency and
      intensity of timber harvests. However, incorporating the influence of forest
      surface albedo often suggests that long rotation lengths may not always be
      optimal in mitigating climate change in forests characterized by frequent
      snowfall. To address this, we investigated trade-offs between three ecosystem
      services: carbon storage, albedo-related radiative forcing, and timber
      provisioning. We calculated optimal rotation length at 498 diverse Forest
      Inventory and Analysis forest sites in the state of New Hampshire, USA. We found
      that the mean optimal rotation lengths across all sites was 94 yr (standard
      deviation of sample means = 44 yr), with a large cluster of short optimal
      rotation lengths that were calculated at high elevations in the White Mountain
      National Forest. Using a regression tree approach, we found that timber growth,
      annual storage of carbon, and the difference between annual albedo in mature
      forest vs. a post-harvest landscape were the most important variables that
      influenced optimal rotation. Additionally, we found that the choice of a baseline
      albedo value for each site significantly altered the optimal rotation lengths
      across all sites, lowering the mean rotation to 59 yr with a high albedo
      baseline, and increasing the mean rotation to 112 yr given a low albedo baseline.
      Given these results, we suggest that utilizing temperate forests in New Hampshire
      for climate mitigation purposes through carbon storage and the cessation of
      harvest is appropriate at a site-dependent level that varies significantly across
      the state.

PMID- 27039517
TI  - Quantifying "apparent" impact and distinguishing impact from invasiveness in
      multispecies plant invasions.
AB  - The quantification of invader impacts remains a major hurdle to understanding and
      managing invasions. Here, we demonstrate a method for quantifying the community
      level impact of multiple plant invaders by applying Parker et al.'s (1999)
      equation (impact = range x local abundance x per capita effect or per unit
      effect) using data from 620 survey plots from 31 grasslands across west-central
      Montana, USA. In testing for interactive effects of multiple invaders on native
      plant abundance (percent cover), we found no evidence for invasional meltdown or
      synergistic interactions for the 25 exotics tested. While much concern exists
      regarding impact thresholds, we also found little evidence for nonlinear
      relationships between invader abundance and impacts. These results suggest that
      management actions that reduce invader abundance should reduce invader impacts
      monotonically in this system. Eleven of 25 invaders had significant per unit
      impacts (negative local-scale relationships between invader and native cover). In
      decomposing the components of impact, we found that local invader abundance had a
      significant influence on the likelihood of impact, but range (number of plots
      occupied) did not. This analysis helped to differentiate measures of invasiveness
      (local abundance and range) from impact to distinguish high-impact invaders from
      invaders that exhibit negligible impacts, even when widespread. Distinguishing
      between high- and low-impact invaders should help refine trait-based prediction
      of problem species. Despite the unique information derived from evaluation of per
      unit effects of invaders, invasiveness 'scores based on range and local abundance
      produced similar rankings to impact scores that incorporated estimates of per
      unit effects. Hence, information on range and local abundance alone was
      sufficient to identify problematic plant invaders at the regional scale. In
      comparing empirical data on invader impacts to the state noxious weed list, we
      found that the noxious weed list captured 45% of the high impact invaders but
      missed 55% and assigned the lowest risk category to the highest-impact invader.
      While such subjective weed lists help to guide invasive species management,
      empirical data are needed to develop more comprehensive rankings of ecological
      impacts. Using weed lists to classify invaders for testing invasion theory is not
      well supported.

PMID- 27039518
TI  - Land-use intensification effects on functional properties in tropical plant
      communities.
AB  - There is consensus that plant diversity and ecosystem processes are negatively
      affected by land-use intensification (LUI), but, at the same time, there is
      empirical evidence that a large heterogeneity can be found in the responses. This
      heterogeneity is especially poorly understood in tropical ecosystems. We
      evaluated changes in community functional properties across five common land-use
      types in the wet tropics with different land-use intensity: mature forest, logged
      forest, secondary forest, agricultural land, and pastureland, located in the
      lowlands of Bolivia. For the dominant plant species, we measured 12 functional
      response traits related to their life history, acquisition and conservation of
      resources, plant domestication, and breeding. We used three single-trait metrics
      to describe community functional properties: community abundance-weighted mean
      (CWM) traits values, coefficient of variation, and kurtosis of distribution. The
      CWM of all 12 traits clearly responded to LUI. Overall, we found that an increase
      in LUI resulted in communities dominated by plants with acquisitive leaf trait
      values. However, contrary to our expectations, secondary forests had more
      conservative trait values (i.e., lower specific leaf area) than mature and logged
      forest, probably because they were dominated by palm species. Functional
      variation peaked at intermediate land-use intensity (high coefficient of
      variation and low kurtosis), which included secondary forest but, unexpectedly,
      also agricultural land, which is an intensely managed system. The high functional
      variation of these systems is due to a combination of how response traits (and
      species) are filtered out by biophysical filters and how management practices
      introduced a range of exotic species and their trait values into the local
      species pool. Our results showed that, at local scales and depending on
      prevailing environmental and management practices, LUI does not necessarily
      result in communities with more acquisitive trait values or with less functional
      variation. Instead of the widely expected negative impacts of LUI on plant
      diversity, we found varying responses of functional variation, with possible
      repercussions on many ecosystem services. These findings provide a background for
      actively mitigating negative effects of LUI while meeting the needs of local
      communities that rely mainly on provisioning ecosystem services for their
      livelihoods.

PMID- 27039519
TI  - How livestock and flooding mediate the ecological integrity of working forests in
      Amazon River floodplains.
AB  - The contribution of working forests to tropical conservation and development
      depends upon the maintenance of ecological integrity under ongoing land use.
      Assessment of ecological integrity requires an understanding of the structure,
      composition, and function and major drivers that govern their variability.
      Working forests in tropical river floodplains provide many goods and services,
      yet the data on the ecological processes that sustain these services is scant. In
      flooded forests of riverside Amazonian communities, we established 46 0.1-ha
      plots varying in flood duration, use by cattle and water buffalo, and time since
      agricultural abandonment (30-90 yr). We monitored three aspects of ecological
      integrity (stand structure, species composition, and dynamics of trees and
      seedlings) to evaluate the impacts of different trajectories of livestock
      activity (alleviation, stasis, and intensification) over nine years. Negative
      effects of livestock intensification were solely evident in the forest
      understory, and plots alleviated from past heavy disturbance increased in
      seedling density but had higher abundance of thorny species than plots
      maintaining low activity. Stand structure, dynamics, and tree species composition
      were strongly influenced by the natural pulse of seasonal floods, such that the
      defining characteristics of integrity were dependent upon flood duration (3-200
      d). Forests with prolonged floods >= 140 d had not only lower species richness
      but also lower rates of recruitment and species turnover relative to forests with
      short floods <70 d. Overall, the combined effects of livestock intensification
      and prolonged flooding hindered forest regeneration, but overall forest integrity
      was largely related to the hydrological regime and age. Given this disjunction
      between factors mediating canopy and understory integrity, we present a subset of
      metrics for regeneration and recruitment to distinguish forest condition by
      livestock trajectory. Although our study design includes confounded factors that
      preclude a definitive assessment of the major drivers of ecological change, we
      provide much-needed data on the regrowth of a critical but poorly studied
      ecosystem. In addition to its emphasis on the dynamics of tropical wetland
      forests undergoing anthropogenic and environmental change, our case study is an
      important example for how to assess of ecological integrity in working forests of
      tropical ecosystems.

PMID- 27039520
TI  - Acceleration and novelty: community restoration speeds recovery and transforms
      species composition in Andean cloud forest.
AB  - Community-based tropical forest restoration projects, often promoted as a win-win
      solution for local communities and the environment, have increased dramatically
      in number in the past decade. Many such projects are underway in Andean cloud
      forests, which, given their extremely high biodiversity and history of extensive
      clearing, are understudied. This study investigates the efficacy of community
      based tree-planting projects to accelerate cloud forest recovery, as compared to
      unassisted natural regeneration. This study takes place in northwest Andean
      Ecuador, where the majority of the original, highly diverse cloud forests have
      been cleared, in five communities that initiated tree-planting projects to
      restore forests in 2003. In 2011, we identified tree species along transects in
      planted forests (n = 5), naturally regenerating forests (n = 5), and primary
      forests (n = 5). We also surveyed 120 households about their restoration methods,
      tree preferences, and forest uses. We found that tree diversity was higher in
      planted than in unplanted secondary forest, but both were less diverse than
      primary forests. Ordination analysis showed that all three forests had distinct
      species compositions, although planted forests shared more species with primary
      forests than did unplanted forests. Planted forests also contained more animal
      dispersed species in both the planted canopy and in the unplanted, regenerating
      understory than unplanted forests, and contained the highest proportion of
      species with use value for local people. While restoring forest increased
      biodiversity and accelerated forest recovery, restored forests may also represent
      novel ecosystems that are distinct from the region's previous ecosystems and,
      given their usefulness to people, are likely to be more common in the future.

PMID- 27039521
TI  - Cascade of ecological consequences for West Nile virus transmission when aquatic
      macrophytes invade stormwater habitats.
AB  - Artificial aquatic habitats are ubiquitous in anthropogenic landscapes and highly
      susceptible to colonization by invasive plant species. Recent research into the
      ecology of infectious diseases indicates that the establishment of invasive plant
      species can trigger ecological cascades which alter the transmission dynamics of
      vector-borne pathogens that imperil human health. Here, we examined whether the
      presence or management of two invasive, emergent plants, cattails (Typha spp.)
      and phragmites (Phragmites australis), in stormwater dry detention basins (DDBs)
      alter the local distribution of vectors, avian hosts, or West Nile virus (WNV)
      transmission risk in an urban residential setting. Mosquitoes and birds were
      surveyed at 14 DDBs and paired adjacent residential sites. During the study
      period, emergent vegetation was mowed by site managers in three DDBs. In the
      absence of vegetation management, the overall abundance and species composition
      of both adult vectors and avian hosts differed between residential and DDB
      habitats; however, WNV entomological risk indices were equivalent. Communal bird
      roosts composed primarily of three species, European Starlings (Sturnus
      vulgaris), Red-winged Blackbirds (Agelaius phoeniceus), and Common Grackles
      (Quiscalus quiscula), representing a broad range of WNV reservoir competence,
      were observed at half (three out of six) of the DDBs containing unmanaged stands
      of phragmites; however, their presence was associated with a lower seasonal
      increase in vector infection rate. Conversely, mowing of emergent vegetation
      resulted in a significant and sustained increase in the abundance of WNV-infected
      vectors in DDBs and the increase in risk extended to adjacent residential sites.
      These findings indicate that management of invasive plants in DDBs during the
      growing season can increase, while presence of communal bird roosts can decrease,
      WNV transmission risk.

PMID- 27039522
TI  - Precision of systematic and random sampling in clustered populations: habitat
      patches and aggregating organisms.
AB  - Natural populations of plants and animals spatially cluster because (1) suitable
      habitat is patchy, and (2) within suitable habitat, individuals aggregate further
      into clusters of higher density. We compare the precision of random and
      systematic field sampling survey designs under these two processes of species
      clustering. Second, we evaluate the performance of 13 estimators for the variance
      of the sample mean from a systematic survey. Replicated simulated surveys, as
      counts from 100 transects, allocated either randomly or systematically within the
      study region, were used to estimate population density in six spatial point
      populations including habitat patches and Matern circular clustered aggregations
      of organisms, together and in combination. The standard one-start aligned
      systematic survey design, a uniform 10 x 10 grid of transects, was much more
      precise. Variances of the 10 000 replicated systematic survey mean densities were
      one-third to one-fifth of those from randomly allocated transects, implying
      transect sample sizes giving equivalent precision by random survey would need to
      be three to five times larger. Organisms being restricted to patches of habitat
      was alone sufficient to yield this precision advantage for the systematic design.
      But this improved precision for systematic sampling in clustered populations is
      underestimated by standard variance estimators used to compute confidence
      intervals. True variance for the survey sample mean was computed from the
      variance of 10 000 simulated survey mean estimates. Testing 10 published and
      three newly proposed variance estimators, the two variance estimators (v) that
      corrected for inter-transect correlation (nu8 and nu(W)) were the most accurate
      and also the most precise in clustered populations. These greatly outperformed
      the two "post-stratification" variance estimators (nu2 and nu3) that are now more
      commonly applied in systematic surveys. Similar variance estimator performance
      rankings were found with a second differently generated set of spatial point
      populations, nu8 and nu(W) again being the best performers in the longer-range
      autocorrelated populations. However, no systematic variance estimators tested
      were free from bias. On balance, systematic designs bring more narrow confidence
      intervals in clustered populations, while random designs permit unbiased
      estimates of (often wider) confidence interval. The search continues for better
      estimators of sampling variance for the systematic survey mean.

PMID- 27039523
TI  - Living shorelines can enhance the nursery role of threatened estuarine habitats.
AB  - Coastal ecosystems provide numerous services, such as nutrient cycling, climate
      change amelioration, and habitat provision for commercially valuable organisms.
      Ecosystem functions and processes are modified by human activities locally and
      globally, with degradation of coastal ecosystems by development and climate
      change occurring at unprecedented rates. The demand for coastal defense
      strategies against storms and sea-level rise has increased with human population
      growth and development along coastlines world-wide, even while that population
      growth has reduced natural buffering of shorelines. Shoreline hardening, a common
      coastal defense strategy that includes the use of seawalls and bulkheads
      (vertical walls constructed of concrete, wood, vinyl, or steel), is resulting in
      a "coastal squeeze" on estuarine habitats. In contrast to hardening, living
      shorelines, which range from vegetation plantings to a combination of hard
      structures and plantings, can be deployed to restore or enhance multiple
      ecosystem services normally delivered by naturally vegetated shores. Although
      hundreds of living shoreline projects have been implemented in the United States
      alone, few studies have evaluated their effectiveness in sustaining or enhancing
      ecosystem services relative to naturally vegetated shorelines and hardened
      shorelines. We quantified the effectiveness of (1) sills with landward marsh (a
      type of living shoreline that combines marsh plantings with an offshore low
      profile breakwater), (2) natural salt marsh shorelines (control marshes), and (3)
      unvegetated bulkheaded shores in providing habitat for fish and crustaceans
      (nekton). Sills supported higher abundances and species diversity of fishes than
      unvegetated habitat adjacent to bulkheads, and even control marshes. Sills also
      supported higher cover of filter-feeding bivalves (a food resource and refuge
      habitat for nekton) than bulkheads or control marshes. These ecosystem-service
      enhancements were detected on shores with sills three or more years after
      construction, but not before. Sills provide added structure and may provide
      better refuges from predation and greater opportunity to use available food
      resources for nekton than unvegetated bulkheaded shores or control marshes. Our
      study shows that unlike shoreline hardening, living shorelines can enhance some
      ecosystem services provided by marshes, such as provision of nursery habitat.

PMID- 27039524
TI  - Reciprocal feedbacks between spatial subsidies and reserve networks in coral reef
      meta-ecosystems.
AB  - Top-down processes such as predation and herbivory have been shown to control the
      dynamics of communities across a range of ecosystems by generating trophic
      cascades. However, theory is only beginning to describe how these local trophic
      processes interact with spatial subsidies in the form of material (nutrient,
      detritus) transport and organismal dispersal to (1) shape the structure of
      interconnected (meta-) ecosystems and (2) determine their optimal management via
      reserve networks. Here, we develop a meta-ecosystem model to understand how the
      reciprocal feedbacks between spatial subsidies and reserve networks modulate the
      importance of top-down control in a simple herbivorous fish-macroalgae-coral
      system. We show that in large and isolated reserve networks where connectivity
      between protected and unprotected areas is limited, spatial subsidies remain
      largely confined to reserves. This retention of spatial subsidies promotes the
      top-down control of corals and macroalgae by herbivores inside reserves but
      reduces it outside reserves. Conversely, in small and aggregated reserves where
      connectivity between protected and unprotected areas is high, the spillover of
      spatial subsidies causes a reduction in top-down control of corals and macroalgae
      by herbivores inside reserves and an increase in the strength of top-down control
      outside reserves. In addition, we demonstrate that there is a trade-off between
      local and regional conservation objectives when designing reserve networks: small
      and aggregated reserves based on the extent of dispersal maximize the abundance
      of corals and herbivores regionally, whereas large and isolated reserves always
      maximize the abundance of corals within reserves, regardless of the extent of
      dispersal. The existence of such "conservation traps," which arise from the
      fulfillment of population-level objectives within local reserves at the cost of
      community-level objectives at regional scales, suggests the importance of
      adopting a more holistic strategy to manage complex and interconnected
      ecosystems.

PMID- 27039525
TI  - Learning about colonization when managing metapopulations under an adaptive
      management framework.
AB  - Adaptive management is a framework for resolving key uncertainties while managing
      complex ecological systems. Its use has been prominent in fisheries research and
      wildlife harvesting; however, its application to other areas of environmental
      management remains somewhat limited. Indeed, adaptive management has not been
      used to guide and inform metapopulation restoration, despite considerable
      uncertainty surrounding such actions. In this study, we determined how best to
      learn about the colonization rate when managing metapopulations under an adaptive
      management framework. We developed a mainland-island metapopulation model based
      on the threatened bay checkerspot butterfly (Euphydryas editha bayensis) and
      assessed three management approaches: adding new patches, adding area to existing
      patches, and doing nothing. Using stochastic dynamic programming, we found the
      optimal passive and active adaptive management strategies by monitoring
      colonization of vacant patches. Under a passive adaptive strategy, increasing
      patch area was best when the expected colonization rate was below a threshold;
      otherwise, adding new patches was optimal. Under an active adaptive strategy, it
      was best to add patches only when we were reasonably confident that the
      colonization rate was high. This research provides a framework for managing
      mainland-island metapopulations in the face of uncertainty while learning about
      the dynamics of these complex systems.

PMID- 27039526
TI  - Estimating wildlife disease dynamics in complex systems using an Approximate
      Bayesian Computation framework.
AB  - Emerging infectious diseases of wildlife are of increasing concern to managers
      and conservation policy makers, but are often difficult to study and predict due
      to the complexity of host-disease systems and a paucity of empirical data. We
      demonstrate the use of an Approximate Bayesian Computation statistical framework
      to reconstruct the disease dynamics of bovine tuberculosis in Kruger National
      Park's lion population, despite limited empirical data on the disease's effects
      in lions. The modeling results suggest that, while a large proportion of the lion
      population will become infected with bovine tuberculosis, lions are a spillover
      host and long disease latency is common. In the absence of future aggravating
      factors, bovine tuberculosis is projected to cause a lion population decline of
      ~3% over the next 50 years, with the population stabilizing at this new
      equilibrium. The Approximate Bayesian Computation framework is a new tool for
      wildlife managers. It allows emerging infectious diseases to be modeled in
      complex systems by incorporating disparate knowledge about host demographics,
      behavior, and heterogeneous disease transmission, while allowing inference of
      unknown system parameters.

PMID- 27039527
TI  - Changes in horn size of Stone's sheep over four decades correlate with trophy
      hunting pressure.
AB  - Selective harvest may lead to rapid evolutionary change. For large herbivores,
      trophy hunting removes males with large horns. That artificial selection,
      operating in opposition to sexual selection, can lead to undesirable consequences
      for management and conservation. There have been no comparisons of long-term
      changes in trophy size under contrasting harvest pressures. We analyzed horn
      measurements of Stone's rams (Ovis dalli stonei) harvested over 37 years in two
      large regions of British Columbia, Canada, with marked differences in hunting
      pressure to identify when selective hunting may cause a long-term decrease in
      horn growth. Under strong selective harvest, horn growth early in life and the
      number of males harvested declined by 12% and 45%, respectively, over the study
      period. Horn shape also changed over time: horn length became shorter for a given
      base circumference, likely because horn base is not a direct target of hunter
      selection. In contrast, under relatively lower hunting pressure, there were no
      detectable temporal trends in early horn growth, number of males harvested, or
      horn length relative to base circumference. Trophy hunting is an important
      recreational activity and can generate substantial revenues for conservation. By
      providing a reproductive advantage to males with smaller horns and reducing the
      availability of desirable trophies, however, excessive harvest may have the
      undesirable long-term consequences of reducing both the harvest and the horn size
      of rams. These consequences can be avoided by limiting offtake.

PMID- 27039528
TI  - Improved estimation of intrinsic growth r(max) for long-lived species:
      integrating matrix models and allometry.
AB  - Intrinsic population growth rate (r(max)) is an important parameter for many
      ecological applications, such as population risk assessment and harvest
      management. However, r(max) can be a difficult parameter to estimate,
      particularly for long-lived species, for which appropriate life table data or
      abundance time series are typically not obtainable. We describe a method for
      improving estimates of r(max) for long-lived species by integrating life-history
      theory (allometric models) and population-specific demographic data (life table
      models). Broad allometric relationships, such as those between life history
      traits and body size, have long been recognized by ecologists. These
      relationships are useful for deriving theoretical expectations for r(max), but
      r(max) for real populations may vary from simple allometric estimators for
      "archetypical" species of a given taxa or body mass. Meanwhile, life table
      approaches can provide population-specific estimates of r(max) from empirical
      data, but these may have poor precision from imprecise and missing vital rate
      parameter estimates. Our method borrows strength from both approaches to provide
      estimates that are consistent with both life-history theory and population
      specific empirical data, and are likely to be more robust than estimates provided
      by either method alone. Our method uses an' allometric constant: the product of
      r(max) and the associated generation time for a stable-age population growing at
      this rate. We conducted a meta-analysis to estimate the mean and variance of this
      allometric constant across well-studied populations from three vertebrate taxa
      (birds, mammals, and elasmobranchs) and found that the mean was approximately 1.0
      for each taxon. We used these as informative Bayesian priors that determine how
      much to "shrink" imprecise vital rate estimates for a data-limited population
      toward the allometric expectation. The approach ultimately provides estimates of
      r(max) (and other vital rates) that reflect a balance of information from the
      individual studied population, theoretical expectation, and meta-analysis of
      other populations. We applied the method specifically to an archetypical petrel
      (representing the genus Procellaria) and to white sharks (Carcharodon carcharias)
      in the context of estimating sustainable-fishery bycatch limits.

PMID- 27039529
TI  - The Golden Age of Material Choices.

PMID- 27039530
TI  - Splints and Occlusion Get No Respect.

PMID- 27039531
TI  - Rella Christensen, RDH, PhD, discusses what it takes to stop a developing carious
      lesion.

PMID- 27039532
TI  - I Haven't Got Time for the Pain.

PMID- 27039533
TI  - Joining Forces. Boston-Based Program Brings Primary Care Into the Dental Clinic.

PMID- 27039534
TI  - "OMG! I Have 'Horsey' Teeth!" Selfie Treachery Leads to Uptick in Visits to UK
      Dentists.

PMID- 27039535
TI  - State by State Prevalence of Periodontal Disease Examined.

PMID- 27039536
TI  - Dental Clinic Opens in Des Moines High School.

PMID- 27039537
TI  - Jaws of Hope. UK Scientists' Shark Teeth Discovery Could Help Humans Grow New
      Teeth.

PMID- 27039538
TI  - Texas Dentists Win the Right to Advertise As Specialists.

PMID- 27039539
TI  - Implant Overdentures.

PMID- 27039540
TI  - A Sequential Approach to Implant-Supported Overdentures.
AB  - Fabrication of implant-supported maxillary or mandibular overdentures can seem to
      be difficult procedures. Many things could go wrong and/or unnoticed until the
      fabrication has been completed. Implants must be correctly surgically placed in
      viable bone at the proper angulation and spacing within an arch. The type of
      attachment must be considered and future treatment of the appliance should be
      simple and efficient. The appliance must function not only initially but also for
      many years to come. The author has found the use of the GPS attachment to be an
      ideal tool to achieve the goals of retention and stability. Careful planning is
      the most important part of this process, and understanding the benefits and risks
      of creating overdentures should be well understood by the dentists. By
      sequentially planning and treating these types of cases, the patient is able to
      function reasonably during the stages of implant healing. The final prosthesis is
      created and remaining teeth that held the transitional appliance in place are
      remove on the day of final seating. This is an excellent simplified retentive
      system option for those patients who are anxious about losing their teeth, even
      those teeth that are diseased and ugly.

PMID- 27039541
TI  - Maximizing Stability and Prosthetic Durability.

PMID- 27039542
TI  - The Single-Stage Implant Procedure: Science or Convenience?

PMID- 27039543
TI  - Cameograms: A New Technique for Prosthodontic Applications.

PMID- 27039544
TI  - Successful and Predictable Custom Complete Dentures.

PMID- 27039545
TI  - The Three Fs of Predictable Endodontics: "Finding, Following, and Finishing".

PMID- 27039546
TI  - Direct Composite Restorations to Mask Intrinsic Staining: An Eighteen-Year Follow
      Up.
AB  - In this case example, the use of direct composite resin allowed for a relatively
      simple, conservative treatment that provided excellent function and aesthetics,
      while preserving healthy dental tissue. The importance of continued follow-up and
      a periodic maintenance and minor repair process will ensure longevity of the
      restorations, as aesthetics, and the occlusion.

PMID- 27039547
TI  - Optimizing a Smile Enhancement: Combining Alignment, Composite Bonding, and
      Ceramic Resurfacing.

PMID- 27039548
TI  - Nurturing nursing students.

PMID- 27039549
TI  - Viewpoint highlights the importance of kindness.

PMID- 27039550
TI  - Valuing patients' humanity.

PMID- 27039551
TI  - Proud to be an aged-care nurse.

PMID- 27039552
TI  - Explaining article's real message.

PMID- 27039553
TI  - Migrant nurses' conference.

PMID- 27039554
TI  - Repairing obstetric fistulas.

PMID- 27039555
TI  - Sky Tower stair challenge.

PMID- 27039556
TI  - Lions donate Transplant House.

PMID- 27039557
TI  - Seeking signatories for petition.

PMID- 27039558
TI  - Genetic muscle disorders study.

PMID- 27039559
TI  - The president comments:.

PMID- 27039560
TI  - Maori nurse numbers to match Maori population by 2028?

PMID- 27039561
TI  - Overseas-trained doctors dominate workforce.

PMID- 27039562
TI  - Public hospital staff bear brunt of belt tightening--Powell.

PMID- 27039563
TI  - New chief executive values her nursing role.

PMID- 27039564
TI  - Improving endoscopy services and reducing waiting lists.

PMID- 27039565
TI  - Intensified masters programmes launched.

PMID- 27039566
TI  - Equal pay offer this month.

PMID- 27039567
TI  - Nurses must be protected if euthanasia legalised--NZNO.

PMID- 27039568
TI  - Thousands protest TPPA signing.

PMID- 27039569
TI  - Half NZ adults have poor health literacy.

PMID- 27039570
TI  - New ministry structure elevates chief nurse role.

PMID- 27039571
TI  - Running health clinics for Sri Lankan workers.

PMID- 27039572
TI  - Grappling with the nursing workforce.

PMID- 27039573
TI  - First-year students favour ePortfolios.

PMID- 27039574
TI  - Breaking down educational silos.

PMID- 27039575
TI  - Leading nursing around the globe.

PMID- 27039576
TI  - Vaccines--how and why they work.

PMID- 27039577
TI  - Supporting students in the Far North.

PMID- 27039578
TI  - Maori nursing degree a unique way to learn.

PMID- 27039579
TI  - Choosing to be an agent for change.

PMID- 27039580
TI  - Student fees on the NSU agenda.

PMID- 27039581
TI  - Challenging the coronial system.

PMID- 27039582
TI  - Eiminating discrimination against women.

PMID- 27039583
TI  - Board revises election code.

PMID- 27039584
TI  - Taking action over lack of nurse entry places.

PMID- 27039585
TI  - Neonatal nursing: A gift to a dying baby and his family.

PMID- 27039586
TI  - Nurse educators: What really matters to patients?

PMID- 27039587
TI  - Stroke education day: Early specialist referral is the key.

PMID- 27039588
TI  - Health informatics: Where are the nurses?

PMID- 27039589
TI  - Gerontology nursing: Stepping up and speaking out.

PMID- 27039590
TI  - Primary health care: A MUCA in Golden Bay--at last.

PMID- 27039591
TI  - Aged care: Proposal to remove ENs from skill mix.

PMID- 27039592
TI  - Industrial staff on the move.

PMID- 27039593
TI  - [If a person wants to do everything by himself, he cannot complain that he has to
      do everything by himself].

PMID- 27039594
TI  - [The threatened loss of privacy by families with chronically ill children by the
      constant presence of the pediatric intensive care nursing service].

PMID- 27039595
TI  - [Families with "special children - focus on cerebral palsy at the "5th Krefeld
      Day of Pediatric Nursing" 21 November 2015"].

PMID- 27039596
TI  - [Epigenetics: interaction of environmental factors on genetic activity].

PMID- 27039597
TI  - [Choice of the suitable birthing site is already critical at the outset].

PMID- 27039598
TI  - [During the night, when everyone or almost everyone sleeps].

PMID- 27039599
TI  - [Is exercise allowed in pregnancy?].

PMID- 27039600
TI  - [Federal government wants to eliminate pediatric nursing].

PMID- 27039601
TI  - [Chronic kidney insufficiency management must become a humanitarian priority].

PMID- 27039602
TI  - [Chronic kidney diseases do not always pass unnoticed].
AB  - Kidney diseases are frequent, but most of the time, they develop unnoticed. This
      paucity of symptoms may lead to delayed diagnosis with important consequences on
      their outcome. Nevertheless, specific systemic signs such as skin lesions, joint
      pain or electrolytes disturbances may sometimes alert the clinician and direct
      the diagnosis to an underlying nephropathy. A high awareness of clinicians is
      warranted to recognize these red flags and diagnose these diseases early, as
      illustrated by two clinical cases discussed in this article.

PMID- 27039603
TI  - [Genetic kidney diseases: new perspectives on diagnosis].
AB  - Suspected renal inherited disorders are regularly evaluated in nephrology
      consultations both in adults and children. A positive family history and/or a
      typical phenotype should lead to genetic investigations. A confirmatory diagnosis
      integrated in a multidisciplinary genetic counseling approach gives patient
      guidance for further pregnancy. It also allows physician to better stratify
      disease risk and indicates treatment in some cases. The time to diagnosis and
      costs have been dramatically reduced thanks to next generation sequencing in
      several cases of complex inherited nephrologic syndromes.

PMID- 27039604
TI  - [Preventive measures of acute renal failure].
AB  - Many conditions can lead to acute renal failure. Some of them are intrinsic renal
      diseases whose natural history cannot be anticipated. On the other hand, others
      correspond to external aggressions driven by various hemodynamic or toxic events.
      To some extent, these can be partially prevented by relatively simple measures.
      The recognition of these situations which may benefit from a preventive strategy
      can significantly reduce morbidity or mortality associated with the incidence of
      acute renal failure.

PMID- 27039605
TI  - [When should the nephrologist be called in the emergency room?].
AB  - Nephrology emergencies are not the most frequent in the emergency room but they
      often generate some diagnostic and therapeutic problems. Most common renal
      emergencies are due most often to acute renal failure whatever the cause,
      electrolytes disturbances, hypertensive crisis and less frequently intoxications
      or acute decompensation of chronic kidney diseases. The goal of this paper is to
      review some of these clinical situations both in the diagnostic and therapeutic
      perspective but essentially to discuss when the nephrologist should be called in
      the emergency room so that the coordination of care is optimal for the patients.

PMID- 27039606
TI  - [Magnesium: the missing link between kidneys and vessels?].
AB  - Chronic kidney disease is highly prevalent worldwide and is associated with
      important cardiovascular morbidity and mortality. The search for new prognostic
      factors and therapeutic targets is therefore essential. There has been recently
      an increased interest about magnesium, poorly studied yet in that context. In
      this article, we review the most recent studies looking at the associations
      between magnesium, cardiovascular and chronic kidney disease. According to the
      available data, hypomagnesemia seems to alter negatively cardiovascular and renal
      prognosis. Maintaining normal magnesium levels could then be protective. However,
      studied populations are heterogeneous, most of the data is only observational and
      residual confounding factors still need to be considered. All those issues limit
      currently any definitive therapeutic recommendations.

PMID- 27039607
TI  - [Overview of peritoneal dialysis].
AB  - Peritoneal dialysis is a dialysis modality used worldwide. Despite offering
      several advantages, its prevalence in Switzerland in end stage renal disease
      population is dramatically lower than hemodialysis (7.3% vs 92.7% in 2014)
      although its incidence has recently progressed. Technically, a catheter is
      inserted into the Douglas' pouch, enabling dialysate to be infused into the
      peritoneal cavity. The peritoneum acts as a semi-permeable membrane allowing for
      the removal of toxic substances and excess water. In the following article we
      will give an overview of peritoneal dialysis including its technical modalities,
      indications and main advantages as well as its contraindications and
      complications.

PMID- 27039608
TI  - [Bio-informatic and personalized medicine: Switzerland is pioneer].

PMID- 27039609
TI  - [Not Available].

PMID- 27039611
TI  - [ORGANS: TAKING THE RISK OF PROCUREMENT WITHOUT EXPLICIT CONSENT?].

PMID- 27039610
TI  - [Not Available].

PMID- 27039612
TI  - [THINK ABOUT LIMITS].

PMID- 27039613
TI  - [A HUNDRED YEAR LATER, FRESH NEWS ON GUILLAIN-BARRE SYNDROME].

PMID- 27039614
TI  - [ATRIA: less anticoagulation for atrial fibrillation?].

PMID- 27039615
TI  - [Shortage of data].

PMID- 27039616
TI  - [MISCELLANEOUS NEWS ON RELIGION, ENTOMOLOGY AND SUICIDES].

PMID- 27039617
TI  - [Geneva: clinics are looking forward to merging].

PMID- 27039618
TI  - [Non-politicized public initiative to favor county subsidies].

PMID- 27039619
TI  - [Praise to instability].

PMID- 27039620
TI  - Finding John Doe. PATIENT MATCHING AND THE NEED FOR A NATIONAL PATIENT SAFETY
      IDENTIFIER.

PMID- 27039621
TI  - MANAGING the SELF-PAY SURGE. HIM PROFESSIONALS FIT FOR PATIENT FINANCIAL ADVOCATE
      ROLES AIDING SELF-PAY PATIENTS.

PMID- 27039622
TI  - Pedaling Out of the HIE Peloton. SOME MASS HIWAY PROVIDERS ARE PULLING AWAY FROM
      THE PACK AND USING HIE FOR TRUE CARE COORDINATION.

PMID- 27039624
TI  - Educating Consumers on Their Privacy, Security Rights.

PMID- 27039623
TI  - Bridging HIM's Disconnect vWith IT. BUILD RELATIONSHIPS FIRST, TACKLE DIFFERENCES
      LATER.

PMID- 27039625
TI  - What Makes Data Meaningful? The Important Role of Data Structures.

PMID- 27039626
TI  - Transforming Data into Meaning: Standards-based Capabilities to Bring Disparate
      Data Sources Together.

PMID- 27039627
TI  - The Information Governance Road Map: Mile Marker 1--Getting Started.

PMID- 27039628
TI  - HIM Best Practices for Records Management at Transitions of Care.

PMID- 27039629
TI  - Calendar Year 2016 OPPS Rule Update.

PMID- 27039630
TI  - ICD-10 Opens Documentation Gaps.

PMID- 27039631
TI  - Looking Ahead to 2016 for What's in Store on Healthcare Policy.

PMID- 27039632
TI  - An Assessment of Performance Between Medicare Advantage and Stand-Alone
      Prescription Drug Plans on Two Quality Assurance Measures.
AB  - The purpose of our study was to compare performance between Medicare Advantage
      and stand-alone prescription drug plans on the two quality assurance measures of
      drug-disease interaction and drug-drug interaction for elderly heart failure
      beneficiaries. Performance on the drug-disease interaction measure appeared more
      problematic for stand-alone plan enrollees compared with Medicare Advantage plan
      enrollees. No statistical difference existed between the plans regarding drug
      drug interactions. It appears there may be considerable room for more
      sophisticated use of disease profiling in the processing of drug claims. The
      provision of richer clinical data is an essential step to improving performance
      on the drug-disease interaction measure.

PMID- 27039633
TI  - Preventing and Recognizing Embezzlement.
AB  - It is estimated that approximately one in six physicians will be the victim of
      embezzlement at least once during his or her lifetime. This may be due to the
      trusting nature of physicians, a lack of business training about separating
      duties in transactions involving money, or employees' feeling overworked,
      underpaid, or underappreciated. The best protection against embezzlement is
      prevention. This article informs the reader of the steps to take to prevent
      stealing in the medical office, how to recognize if it is occurring, and how to
      obtain restitution or prosecution.

PMID- 27039634
TI  - Opening the Door to Patient Retention: A Look at New Technology Trends.
AB  - What is the number one factor that shapes a patient's overall opinion of his or
      her medical practitioner and fosters the loyalty we all seek? The answer might
      surprise you, and you may find that you have been using your resources
      ineffectively. This article uncovers the latest technology trends for retaining
      and reactivating your patients, an approach that is much more cost effective than
      constantly bringing in new patients as others go out the back door. We also look
      at a couple of recent studies that blow the lid off traditional thinking with
      regard to patient communication and practice loyalty. The result will be an
      increased recognition of what drives and motivates patients. Find out how your
      practice can use the newest technology to streamline and simplify a number of
      important, but ordinary, communication processes to help keep patients engaged.
      Effective, ongoing, and timely communication not only enhances the patient
      experience, it also increases staff efficiency and helps your office run more
      smoothly.

PMID- 27039635
TI  - Phase 2 HIPAA Audits for Providers and Business Associates on the Horizon.

PMID- 27039636
TI  - Hospital Contracts: Important Issues for Medical Groups.
AB  - Relationships with hospitals and outpatient medical facilities have always been
      an important part of the business model for private medical practices. As
      healthcare delivery to patients has evolved in the United States (much of it
      driven by the new government mandates, regulations, and the Affordable Care Act),
      the delivery of such services is becoming more and more centered on the hospital
      or institutional setting, thus making contractual relationships with hospitals
      even more important for medical practices. As a natural outgrowth of this
      relationship, attention to hospital contracts is becoming more important.

PMID- 27039637
TI  - Increasing Medical Practice Team Commitment: Twenty-Five Strategies.
AB  - Employee commitment is one of the most important principles of practice man-
      agement. Yet commitment is delicate; it must be carefully earned, and it can
      easily deteriorate. This article explores practical strategies the medical
      practice manager can use to assess, foster, and increase employee commitment. It
      de- fines commitment and how commitment is manifested in employee attitudes and
      behavior. It provides a 10-question guide medical practice managers can use to
      assess employee commitment, and a four-part roadmap that will inspire commitment
      through leadership. This article also offers 25 hands-on strate- gies to increase
      employee commitment, and more than a dozen questions to guide difficult
      conversations with employees when their commitment level to the medical practice
      is low or unclear. Finally, this article suggest four drivers of employee
      commitment and a five-part strategy medical practice managers can use to model
      commitment through their own leadership.

PMID- 27039638
TI  - Medicare Physician Fee Schedule Ends at Age 26: Succeeding in an Era of Payment
      Reform.
AB  - The Medicare Access and CHIP Reauthorization Act of 2015 solidifies healthcare
      payment reform by signaling the death of traditional fee-for-service
      reimbursement for providers. Effective 2019, Medicare payments will rely heavily
      on data, risk-sharing, and transparency to advance value over volume. Other
      payers will follow.

PMID- 27039639
TI  - Professional Liability Pertinent to Graduate Medical Education: The Intersection
      of Medical Education, Patient Care, and Law.
AB  - Physicians in training, nurse practitioners, physician assistants, attending
      physicians, and institutions that sponsor medical education are all at risk for
      potential professional liability issues. The unique relationship between
      healthcare providers and their sponsoring institution generates complex and
      evolving legal issues for all participants in medical education training. The law
      has played a great role integrating quality care and patient safety with
      excellent medical education for training physicians, while providing an avenue
      for relief when a medical error occurs. The intersection of law and medicine,
      while allowing for optimal medical education and patient care, exposes
      participating medical providers and the sponsoring institutions to specific
      professional liability issues. This article addresses these medical education
      settings and their potential professional liability issues.

PMID- 27039640
TI  - Crowd Sourcing.
AB  - The Internet has contributed new words and slang to our daily vernacular. A few
      terms, such as tweeting, texting, sexting, blogging, and googling, have become
      common in most vocabularies and in many languages, and are now included in the
      dictionary. A new buzzword making the rounds in industry is crowd sourcing, which
      involves outsourcing an activity, task, or problem by sending it to people or
      groups outside a business or a practice. Crowd sourcing allows doctors and
      practices to tap the wisdom of many instead of relying only on the few members of
      their close-knit group. This article defines "crowd sourcing," offers examples,
      and explains how to get started with this approach that can increase your ability
      to finish a task or solve problems that you don't have the time or expertise to
      accomplish.

PMID- 27039641
TI  - When the Going Gets Tough: When Isn't It Tough?.

PMID- 27039642
TI  - Tactful Communication: Settling Disputes.
AB  - Tact is the ability to speak to others in a manner that is not offensive or
      hurtful of others' feelings. Practices should coach staff on verbiage and body
      language that encourage respect, kindness, and understanding. Being sensitive to
      the feelings of others is a skill that everyone should develop.

PMID- 27039644
TI  - Public Speaking: Managing Challenging People and Situations.
AB  - Every public speaker has encountered, or most likely will encounter, a difficult
      member of the audience who disrupts their presentation. This is a source of
      anxiety and discomfort, not only for the presenter, but for the audience as well.
      Learning how to manage the disruptive audience member is an art form, just like
      being a good public speaker. A professional speaker knows how to handle this
      disruption without making the audience uncomfortable and without embarrassing the
      disruptor. This article discusses ways to manage the disruptive audience member
      and will help those of you who do public speaking to tactfully and professionally
      disengage someone who is ruining your program.

PMID- 27039643
TI  - The New World of Interaction Recording for Medical Practices.
AB  - Today's medical practice staff communicates remotely with patients, pharmacies,
      and other medical providers in new ways that go far beyond telephone calls.
      Patient care and communication are now being provided via telecommunications
      technologies, including chat/IM, screen, Skype, and other video applications.
      This new paradigm in patient care, known as "telehealth" or "telemedicine," could
      put medical practices at risk for noncompliance with strict HIPAA and other
      regulations. Interaction recording encompasses these new means of communication
      and can help medical practice staff achieve compliance and reduce financial and
      liability risks while improving operations and patient care. This article
      explores what medical practices need to know about interaction recording, what to
      look for in an interaction recording solution, and how to best utilize that
      solution to meet compliance, manage liability, and improve patient care.

PMID- 27039645
TI  - How to Survive the Next Five Years.
AB  - The rapid pace of change in medical practice combined with increasingly heavy
      regulation has created a negative mindset for many practitioners. Although the
      future of medical practice is uncertain, there are fundamentals that, if
      understood, can ensure the success of private practitioners. These include
      efficient practice management and effective practice marketing.

PMID- 27039646
TI  - EXERCISE 101. Commit to it.

PMID- 27039647
TI  - The Right Fit.

PMID- 27039648
TI  - Count down to camp.

PMID- 27039649
TI  - New ADA Guidelines: How Much Do You Know? Test Your Knowledge of the Latest
      Advice on Diabetes Care.

PMID- 27039650
TI  - PCOS: Polycystic Ovarian Syndrome.

PMID- 27039651
TI  - READY, SET, go!.

PMID- 27039652
TI  - Eating well on a Budget.

PMID- 27039653
TI  - Take 5.

PMID- 27039654
TI  - GAME DAY. Touchdown!

PMID- 27039655
TI  - SOUPS & STEWS. Cool Air, Warm Bowls.

PMID- 27039656
TI  - HEALTHY EATING. Resolution Ready.

PMID- 27039657
TI  - DATE NIGHT. Cooking for Two.

PMID- 27039658
TI  - Supermarket smarts. Tortilla Chips.

PMID- 27039659
TI  - Sean Walsh.

PMID- 27039660
TI  - Inhibition of Photodegradation of Highly Dispersed Folic Acid Nanoparticles by
      the Antioxidant Effect of Transglycosylated Rutin.
AB  - We developed highly dispersible and photostable nanoparticles of vitamin, folic
      acid (FA). FA was wet bead milled with milling and dispersing adjuvants and
      transglycosylated compounds such as alpha-glucosyl hesperidin (Hesperidin-G) and
      rutin (Rutin-G), which solubilized FA. The milled slurries of FA particles with
      transglycosylated compounds consisted of nanosized particles with a median
      diameter of <100 nm. The lyophilized formulations of these slurries retained
      their nanometer size after resuspension in water with no aggregation. The
      apparent solubility of FA in these formulations was 100-fold higher than that of
      untreated FA. The solubilizing effect of Rutin-G may affect the particle size
      reduction and dispersibility of FA. The photostability results showed that the
      strong antioxidant activity of Rutin-G substantially increased the photostability
      of FA solution. On the basis of these results, bead milling of FA with Rutin-G is
      a promising technique for developing highly dispersible, photostable nanoparticle
      FA formulations. 

PMID- 27039661
TI  - Behavioral and neural impairments of frontotemporal dementia: Potential
      implications for criminal responsibility and sentencing.
AB  - Individuals in the early stages of the behavioral variant of frontotemporal
      dementia (bvFTD), a progressive neurodegenerative disorder marked by atrophy to
      the brain's frontal regions, exhibit severe disturbances to social and moral
      processing and decision-making after the onset of the disorder. These behavioral
      impairments, underlain by the neural deficits associated with the disorder, can
      often lead individuals with bvFTD to criminally offend. As such, behavioral and
      frontotemporal lobe abnormalities exhibited by offenders with bvFTD potentially
      represent several complex challenges for the legal system. This paper examines
      some of the ways in which the behavioral and neural impairments associated with
      bvFTD may influence issues surrounding the criminal responsibility, specifically
      legal insanity, and sentencing of offenders with bvFTD in the U.S. legal system.
      As there is very little literature in these areas concerning bvFTD, the existing
      academic dialogue on psychopathy, a disorder with similar behavioral symptoms and
      neural deficits, is used to frame the discussion on these issues.

PMID- 27039662
TI  - Analysis of the transmission of Trypanosoma cruzi infection through hosts and
      vectors.
AB  - Calculating epidemiological measures of infection by Trypanosoma cruzi, the
      causative agent of Chagas disease, is complex, because it involves several
      species, different stages of infection in humans and multiple transmission
      routes. Using the next-generation matrix method, we analysed a model which
      considers the three stages of human infection, triatomines and dogs (the main
      domestic reservoirs of T. cruzi when triatomines are present) and the main
      transmission routes. We derived R 0 and type-reproduction numbers T. We deduced
      formulas for the number of new infections generated through each transmission
      route by each infected individual. We applied our findings in Argentine Gran
      Chaco. The expressions achieved allowed quantifying the high infectivity of dogs
      and emphasizing the epidemiological importance of the long and asymptomatic
      chronic indeterminate stage in humans in the spread of the infection. According
      to the model, it is expected that one infected human infects 21 triatomines, that
      100 infected triatomines are necessary to infect one human and 34 to infect a
      dog, and that each dog infects on average one triatomine per day. Our results may
      allow quantifying the effect of control measures on infected humans, triatomines
      and dogs (or other highly infected vertebrate) or on a specific route of
      transmission, in other scenarios.

PMID- 27039663
TI  - AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting
      protein 4.
AB  - Our previous studies have shown that PRKA kinase anchor protein 9 (AKAP-9) is
      involved in colorectal cancer (CRC) cell proliferation and migration in vitro.
      However, whether or not AKAP-9 is important for CRC development or metastasis in
      vivo remains unknown. In the present study, we found that AKAP-9 expression was
      significantly higher in human colorectal cancer tissues than the paired normal
      tissues. In fact, AKAP-9 level correlated with the CRC infiltrating depth and
      metastasis. Moreover, the higher AKAP-9 expression was associated with the lower
      survival rate in patients. In cultured CRC cells, knockdown of AKAP-9 inhibited
      cell proliferation, invasion, and migration. AKAP-9 deficiency also attenuated
      CRC tumor growth and metastasis in vivo. Mechanistically, AKAP-9 interacted with
      cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were
      interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential
      for TGF-beta1-induced epithelial-mesenchymal transition of CRC cells, and CIP4
      played a critical role in mediating the function of AKAP-9. Importantly, CIP4
      expression was significantly up-regulated in human CRC tissues. Taken together,
      our results demonstrated that AKAP-9 facilitates CRC development and metastasis
      via regulating CIP4-mediated epithelial-mesenchymal transition of CRC cells.

PMID- 27039664
TI  - Deliberate body disposal by hominins in the Dinaledi Chamber, Cradle of
      Humankind, South Africa?

PMID- 27039665
TI  - Migration-related tuberculosis: epidemiology and characteristics of tuberculosis
      cases originating outside the European Union and European Economic Area, 2007 to
      2013.
AB  - Migrants arriving from high tuberculosis (TB)-incidence countries may pose a
      significant challenge to TB control programmes in the host country. TB
      surveillance data for 2007-2013 submitted to the European Surveillance System
      were analysed. Notified TB cases were stratified by origin and reporting country.
      The contribution of migrant TB cases to the TB epidemiology in EU/EEA countries
      was analysed. Migrant TB cases accounted for 17.4% (n = 92,039) of all TB cases
      reported in the EU/EEA in 2007-2013, continuously increasing from 13.6% in 2007
      to 21.8% in 2013. Of 91,925 migrant cases with known country of origin, 29.3%
      were from the Eastern Mediterranean, 23.0% from south-east Asia, 21.4% from
      Africa, 13.4% from the World Health Organization European Region (excluding
      EU/EEA), and 12.9% from other regions. Of 46,499 migrant cases with known drug
      susceptibility test results, 2.9% had multidrug-resistant TB, mainly (51.7%)
      originating from the European Region. The increasing contribution of TB in
      migrants from outside the EU/EEA to the TB burden in the EU/EEA is mainly due to
      a decrease in native TB cases. Especially in countries with a high proportion of
      TB cases in non-EU/EEA migrants, targeted prevention and control initiatives may
      be needed to progress towards TB elimination. 

PMID- 27039666
TI  - More HOPE for Prevention with Statins.

PMID- 27039667
TI  - Miltefosine lipid nanocapsules: Intersection of drug repurposing and
      nanotechnology for single dose oral treatment of pre-patent schistosomiasis
      mansoni.
AB  - A dual drug repurposing/nanotechnological approach was used to develop an
      alternative oral treatment for schistosomiasis mansoni using miltefosine (MFS),
      an anticancer alkylphosphocholine, and lipid nanocapsules (LNCs) as oral
      nanovectors. We demonstrated earlier that MFS possesses significant activity
      against different developmental stages of Schistosoma mansoni in the mouse model
      using 5 successive 20mg/kg/day oral doses. Moreover, an effective single dose
      (20mg/kg) oral treatment against the adult stage of S. mansoni in mice was
      developed using LNCs, particularly modified with CTAB, a positive charge
      imparting agent (MFS-LNC-CTAB(+)), or oleic acid as membrane permeabilizer (MFS
      LNC-OA). Efficacy enhancement involved, at least in part, targeting of the worm
      tegument with MFS-LNCs as a new therapeutic entity. As the tegument surface
      charge and composition may differ in pre-patent stages of the parasite, it was of
      importance in the present study to assess the efficacy of a single oral dose of
      the two MFS-LNC formulations against invasive and immature stages for potential
      advantage relative to praziquantel. Results indicated potent schistosomicidal
      effects against both invasive and immature stages of S. mansoni in infected mice,
      efficacy being both formulation and developmental stage dependent. This was
      indicated by the significant reduction in the total worm burden of the invasive
      stage by 91.6% and 76.8% and the immature stage by 82.7% and 96.7% for MFS-LNC
      CTAB+ and MFS-LNC-OA, respectively. Histopathological findings indicated
      amelioration of hepatic pathology with regression of the granulomatous
      inflammatory reaction and reduction in granulomas number and size, verifying
      marked improvement in architecture of hepatic lobules. From a clinical
      perspective, MFS-LNCs offer potential as an alternative single oral dose
      nanomedicine with a wide therapeutic profile for the mass chemotherapy of
      schistosomiasis mansoni. 

PMID- 27039668
TI  - Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of
      systemic hydroa vacciniforme and hypersensitivity to mosquito bites.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural killer (NK)
      lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and
      hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases
      are still unclear. OBJECTIVE: To understand the inflammatory process, we examined
      EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from
      patients with EBV-associated T/NK-LPDs. METHODS: Sixty-four patients with EBV
      associated LPDs and epithelial neoplasms, and EBV+ cell line cells were studied.
      DNase-treated and resistant EBV DNA load in blood and cell culture supernatants
      were calculated. An EBV reactivation signal was analyzed in the tissue, blood and
      cell line cells. RESULTS: In the tissue, BZLF1 mRNA was detected in 5 of 6 (83%)
      samples of EBV+ epithelial neoplasms, 16 of 21 (76%) of EBV+ lymphomas, and 5 of
      15 (33%) of systemic HV and/or HMB, but negative in all 15 patients with
      classical HV. In the blood, BZLF1 mRNA was detected in only one of 19 (5.3%)
      samples of EBV-associated T/NK-LPDs. A down-stream reactivation signal, BDRF1
      mRNA was expressed in all 6 samples of EBV+ epithelial neoplasms, but it was
      positive in only one of 15 (6.7%) samples from systemic HV and HMB in the tissue.
      EBV+ T/NK-cell line cells treated with phorbol 12-myristate 13-acetate produced
      BZLF1 and BDRF1 mRNA, and encapsidated EBV DNA was detected in the culture
      supernatants of cell line cells. CONCLUSION: Stimulation-induced EBV reactivation
      occurred both in vivo and in vitro, but it was almost abortive in vivo.
      Reactivation-related EBV antigens might be responsible for induction of systemic
      HV and HMB.

PMID- 27039669
TI  - Preoperative patient-reported scores can predict postoperative outcomes after
      shoulder arthroplasty.
AB  - BACKGROUND: Total shoulder arthroplasty and reverse total shoulder arthroplasty
      are increasingly used to improve pain and function in patients with glenohumeral
      arthritis or cuff tear arthropathy. Our objective was to determine if
      preoperative patient-reported outcome measures predict which patients will
      achieve clinically meaningful improvements after shoulder arthroplasty. METHODS:
      Preoperative and 1-year postoperative 12-Item Short Form Health Survey (SF-12)
      Physical Component Summary (PCS) and Mental Component Summary (MCS) scores and
      American Shoulder and Elbow Surgeons (ASES) pain and function scores were
      prospectively collected from 107 patients who underwent total or reverse shoulder
      arthroplasty. The minimum clinically important difference (MCID) defined
      meaningful clinical improvement. Receiver operating characteristic analysis was
      used to calculate threshold values and C statistic. Multivariate logistic
      regression analysis was performed to determine preoperative measures that were
      indicative of achieving the MCID postoperatively. RESULTS: Threshold values below
      which patients were more likely to achieve MCID were 12 for ASES function, 25 for
      ASES pain, 46 for SF-12 PCS, and 42 for SF-12 MCS. Multivariate analysis revealed
      that preoperative ASES function (area under the curve, 0.79; P = .006) and ASES
      pain (area under the curve, 0.90; P < .001) measures were predictive of achieving
      the MCID postoperatively. Patients with higher preoperative SF-12 MCS scores had
      a higher likelihood of achieving MCID for each measure. CONCLUSION: We determined
      threshold values that predict clinically meaningful improvement after shoulder
      arthroplasty. Patients with higher preoperative mental health scores and lower
      physical function and pain scores were more likely to gain significant benefits
      from surgery. These results can be used to facilitate shared decision-making and
      to forecast expected benefits after shoulder arthroplasty.

PMID- 27039670
TI  - Ulnar neuritis after open elbow arthrolysis combined with ulnar nerve
      subcutaneous transposition for post-traumatic elbow stiffness: outcome and risk
      factors.
AB  - BACKGROUND: Ulnar neuritis (UN) is a common complication of open elbow
      arthrolysis for elbow stiffness. The purpose of this study was to evaluate the
      outcome of subcutaneous anterior transposition of the ulnar nerve during open
      elbow arthrolysis and to describe the risk factors for UN. METHODS: We
      retrospectively studied 260 patients with post-traumatic elbow stiffness who
      underwent routine ulnar nerve transposition during open elbow arthrolysis.
      Patient demographics, clinical characteristics, and incidence and reoperation
      rate of UN were recorded. UN was defined as new-onset ulnar nerve symptoms and no
      relief or worsening of pre-existing ulnar nerve symptoms during the period of
      postoperative rehabilitation. Factors affecting the development of UN were
      analyzed by univariate and multivariate analyses. RESULTS: A total of 9.2% of the
      patients had UN, 25% of whom required reoperation for progressive neuropathy. The
      Dellon grade of patients associated with UN at last follow-up improved
      significantly compared with that preoperatively. The mean arc of motion in
      patients with UN decreased during follow-up in a time-dependent manner.
      Univariate analysis showed that male sex, limited preoperative flexion and arc of
      motion, preoperative heterotopic ossification (HO), and preoperative ulnar nerve
      symptoms were significantly associated with the development of UN. Multivariate
      regression analysis revealed that preoperative HO was the only independent risk
      factor for the development of UN. CONCLUSIONS: UN is still an important
      complication, although ulnar nerve subcutaneous transposition was performed
      during open arthrolysis for post-traumatic elbow stiffness. Identified risk
      factors for UN, especially preoperative HO, should be taken into consideration
      before surgery.

PMID- 27039671
TI  - Reverse total shoulder arthroplasty with structural bone grafting of large
      glenoid defects.
AB  - BACKGROUND: Large glenoid defects pose difficulties in shoulder arthroplasty.
      Structural grafts consisting of a humeral head autograft, iliac crest, and
      allograft have been described. Few series describe grafts used with reverse total
      shoulder arthroplasty (RTSA). METHODS: We retrospectively reviewed patients who
      had undergone primary or revision RTSA. We identified 44 patients (20 men and 24
      women; mean age, 69 years) as having a bulk structural graft to the glenoid
      behind the baseplate. The grafts consisted of a humeral head autograft in 29,
      iliac crest autograft in 1, or femoral head allograft in 14. Range of motion
      data, American Shoulder and Elbow Surgeons score, simple shoulder test, shoulder
      pain and disability index, and Constant scores were obtained from preoperative
      and the latest follow-up visits. Radiographs were reviewed from the initial
      postoperative visit and the latest follow-up. The grafting cohort was compared
      with an age- and sex-matched cohort of RTSA patients without glenoid grafting.
      RESULTS: Improvements were seen in the functional outcome scores at the latest
      follow-up. No significant differences were found in the preoperative or
      postoperative data between allografts and autografts. Postoperative scores for
      the bone graft cohort were significantly lower than those in the cohort without
      grafting. Complete or partial incorporation was shown radiographically in 81% of
      grafts. Six baseplates were considered loose. Complications included 2
      infections, 1 dislocation, 1 humeral loosening, and 2 instances of clinical
      aseptic baseplate loosening. Six patients showed mild scapular notching.
      CONCLUSIONS: The use of bulk structural grafts is a promising treatment option.
      Allografts may yield equally acceptable results compared with autografts.

PMID- 27039672
TI  - Joint capsule attachment to the coronoid process of the ulna: an anatomic study
      with implications regarding the type 1 fractures of the coronoid process of the
      O'Driscoll classification.
AB  - BACKGROUND: The attachment of the anterior joint capsule on the ulnar coronoid
      process is not yet completely understood. The purpose of this study was to
      clarify the anatomic relationship between the anterior capsule of the elbow joint
      and the tip of the coronoid process. METHODS: Seventeen embalmed elbows were used
      for this anatomic study. The anterior capsule of the elbow joint was reflected,
      and the attachment of the capsule on the coronoid process was exposed. The
      attachment of the joint capsule on the coronoid process was macroscopically and
      histologically observed, its relationship to the coronoid tip was assessed, and
      the length of the attachment of the joint capsule was measured. RESULTS: The
      length of the capsule attachment at the radial side of the coronoid (11.9 mm) was
      greater than that at the ulnar side (6.1 mm). The bone thickness on the coronoid
      tip from the proximal edge of the joint capsule attachment was 1.9 mm; together,
      the cartilage and bone thickness was 4.7 mm. At the radial side of the coronoid,
      the thickness of the joint capsule at the proximal aspect of the attachment of 2
      samples was 0.6 mm and 0.3 mm, and that at the tip of the coronoid was 2.6 mm and
      1.7 mm, respectively. CONCLUSIONS: The anterior capsule of the elbow joint had a
      substantial attachment on the radial side of the coronoid process. The subtype 2
      tip fractures of the O'Driscoll classification included the joint capsule
      attachment, joint cartilage, and subchondral bone.

PMID- 27039673
TI  - The effect of myofibroblasts and corticosteroid injections in adhesive
      capsulitis.
AB  - HYPOTHESIS: Adhesive capsulitis is a condition that results in restricted
      glenohumeral motion. Fibroblasts have been implicated in the disease process;
      however, their role as a contractile element in the development of fibrosis and
      capsular contracture is not well understood. We hypothesized (1) that
      myofibroblast prevalence in capsular biopsy specimens from patients with adhesive
      capsulitis would be increased compared with controls and (2) that patients
      treated with an intra-articular injection of corticosteroid would have fewer
      myofibroblasts. METHODS: The study prospectively enrolled 20 consecutive patients
      with adhesive capsulitis scheduled for capsular release and matched controls.
      Tissue samples were collected from the posterior and anterior capsule for
      histomorphologic and immunohistologic analyses. Identical sectioning and
      preparation was performed in 14 additional adhesive capsulitis specimens from
      patients who had not received corticosteroid injections. RESULTS: Patients with
      adhesive capsulitis not treated with preoperative corticosteroid demonstrated
      more histologic evidence of fibromatosis, synovial hyperplasia, and an increase
      in positive staining for alpha-smooth muscle actin than patients who had received
      intra-articular injections of steroid. No specimens obtained from control
      patients demonstrated positive staining for alpha-smooth muscle actin.
      DISCUSSION: There was a higher prevalence of myofibroblast staining in patients
      with adhesive capsulitis, implicating activation of the myofibroblast in the
      pathophysiology of capsular contracture. Intra-articular steroid injection
      decreases the presence and amount of fibromatosis, vascular hyperplasia,
      fibrosis, and the presence of fibroblasts staining for alpha-smooth muscle actin.
      This supports the use of steroid injections to alter the disease process by
      decreasing the pathologic changes found in the capsular tissue.

PMID- 27039674
TI  - Distal biceps reconstruction using an Achilles tendon allograft, transosseous
      EndoButton, and Pulvertaft weave with tendon wrap technique for retracted,
      irreparable distal biceps ruptures.
AB  - BACKGROUND: Distal biceps ruptures can result in ongoing pain and weakness when
      treated nonoperatively. If retraction of the tendon renders primary repair
      impossible, reconstruction using a graft is recommended. The current literature
      includes a variety of techniques with studies reporting small patient numbers.
      The aim of this study was to report the results of a larger cohort of patients
      using a technique modified from those previously described in the literature.
      METHODS: Twenty-one consecutive male patients underwent distal biceps
      reconstruction through 2 small anterior incisions using an Achilles tendon
      allograft that was fixed distally using a transosseous EndoButton and secured
      proximally using a Pulvertaft weave and tendon wrap. The mean age was 44 years,
      and the mean time to surgery was 25 months (range, 2-96 months). Functional
      outcomes were collected prospectively. RESULTS: The mean preoperative Quick
      Disabilities of the Arm, Shoulder and Hand (QuickDASH) score (11 patients) was
      1.9 (range, 0-4.5). The mean postoperative Oxford Elbow Score, QuickDASH score,
      and Mayo Elbow Performance Score were 44.7 (range, 35-48), 4 (range, 0-20.5), and
      92.9 (range, 70-100), respectively, at a mean follow up of 15 months (range, 6-35
      months). The mean postoperative QuickDASH score was significantly improved
      compared with preoperatively (P < .001). All patients were satisfied and all
      returned to their previous level of activity. There were 2 transient lateral
      antebrachial cutaneous nerve paresthesias, and 2 patients had a 5 degrees 
      extension lag. There were no other complications. CONCLUSION: Achilles allograft
      reconstruction of retracted irreparable distal biceps ruptures provides
      consistently good results with few complications using this technique.

PMID- 27039675
TI  - The Arthroscopy Journal Experience: Tailored for You and by You.
AB  - As editors, we not only oversee the peer-review process to select the most timely
      and relevant content but also strive to group the articles we accept for
      publication in a way that best fulfills your expectations and needs as readers.
      The Internet has impacted not only how we review but also how we publish and how
      you read. We invite you to take advantage of Arthroscopy's many web-based
      features to tailor your reading experience. 

PMID- 27039676
TI  - Synthetic Grafts.

PMID- 27039677
TI  - Editorial Commentary: Save the Subchondral Bone in Rotator Cuff Repair Greater
      Tuberosity Preparation.
AB  - Results from a recent investigation into the practice of greater tuberosity
      decortication before rotator cuff repair showed that decortication significantly
      reduced the ultimate failure load. Although the potential of greater tuberosity
      treatment for solving the rotator cuff healing quandary still exists, the
      biomechanics are clear, one should not decorticate the greater tuberosity to
      cancellous bone. 

PMID- 27039678
TI  - Editorial Commentary: Teres Minor Fatty Infiltration on Magnetic Resonance
      Imaging--Have You Considered It, and Does It Matter When Performing Rotator Cuff
      Repairs?
AB  - Rotator cuff repair can be performed without a great deal of concern in the
      presence of fatty infiltration in the teres minor. 

PMID- 27039679
TI  - Editorial Commentary: To Screw or to Sew--Which Is Better for Arthroscopic Biceps
      Tenodesis?
AB  - As the popularity of arthroscopic biceps tenodesis continues to grow, surgeons
      must choose between performing a soft-tissue tenodesis and performing a bony
      tenodesis. Although there is no difference in visual analog scale, Constant, or
      American Shoulder and Elbow Surgeons scores at greater than 2 years' follow-up,
      elbow flexion strength index and fixation failure rates favor bony tenodesis,
      important factors to consider when deciding which procedure to perform.

PMID- 27039680
TI  - Editorial Commentary: Is Lateral Acromioplasty Effective and Safe?
AB  - Reduction of critical shoulder angle to less than 35 degrees  is potentially
      useful to prevent progression of rotator cuff tear or to protect cuff repair from
      re-tear. Lateral acromioplasty is an effective procedure to reduce the critical
      shoulder angle without violating the acromial deltoid origin. 

PMID- 27039681
TI  - Editorial Commentary: Many Ways to Skin a Cat.
AB  - There are many ways to treat lateral epicondylitis. The authors of this study
      present 2 different methods, but one method has less operative cost and takes
      less time. As medicine evolves, we should take this into account when choosing
      one procedure over another.

PMID- 27039682
TI  - Editorial Commentary: Do Our Hip Arthroscopy Patients End Up With a Shiny New
      Hip?
AB  - In a cohort of over 7,000 patients, the rate of conversion to total hip
      arthroplasty after hip arthroscopy was 12.4%. Increased age, the presence of
      osteoarthritis, the presence of obesity, and low surgeon volume were all
      independent risk factors for a higher rate of revision. 

PMID- 27039683
TI  - Editorial Commentary: Workers' Compensation and Hip Arthroscopy.
AB  - Patients with active claims for workplace injuries will benefit from treatment
      for femoroacetabular impingement, but improvement is not as good as in the
      patients with sports-related injuries. Workers' Compensation patients differ from
      highly motivated athletes. 

PMID- 27039684
TI  - Editorial Commentary: How to Achieve Accurate Graft Placement in Lateral Meniscal
      Allograft Transplantation.
AB  - The lateral tibial spine may not be a reliable reference for determining the
      direction of the guide pin for the keyhole in the lateral meniscal allograft
      transplantation procedure. Supplemental landmarks may be required to improve the
      accuracy in graft placement.

PMID- 27039685
TI  - Editorial Commentary: Does Early Arthroscopy of Subtle Instability in High Ankle
      Sprains Hasten Return to Play in Elite Athletes?
AB  - Anterior inferior tibial fibular ligament tenderness to palpation, a positive
      squeeze test, and a positive external rotation test correlate well with
      syndesmosis instability after high ankle sprain. However, it is still unknown
      whether subtle unstable high ankle sprains (grade IIB) could heal satisfactorily
      with nonoperative treatment and whether their recovery would be prolonged
      compared with operative treatment.

PMID- 27039686
TI  - Editorial Commentary: On Kibler & Sciascia: What Did the Five Fingers Say to the
      Face? SLAP. A Systematic Review Wake-Up Call to Improve SLAP Repair Guidelines.
AB  - Both the quality and quantity of reporting in the SLAP repair literature,
      especially the surgical indications and technical intraoperative characteristics,
      leaves significant room for improvement. In their systematic review, Kibler and
      Sciascia identify this considerable underlying imprecision. Based on the current
      literature, no consensus exists for establishing any criteria for a successful
      SLAP repair--surgical indications, characteristics (type, location, number of
      anchors), completeness of repair, or rehabilitation.

PMID- 27039687
TI  - Vaccination of calves against common respiratory viruses in the face of
      maternally derived antibodies(IFOMA).
AB  - Vaccination of calves in the face of maternal antibodies (IFOMA) often does not
      result in seroconversion as maternally derived immunity interferes with the
      activation of adequate antibody responses to vaccination; however, it can prime T
      and B cell memory responses that protect calves against clinical disease when
      maternal immunity has decayed. The activation of B and T cell memory responses in
      calves vaccinated IFOMA varies and is affected by several factors, including age,
      level of maternal immunity, type of vaccine, and route of administration. These
      factors influence the adequate priming of humoral and cell mediated immune
      responses and the outcome of vaccination. The failure to adequately prime immune
      memory after vaccination IFOMA could result in lack of clinical protection and
      increased risk of viremia and/or virus shedding.

PMID- 27039688
TI  - Macrophage Cell Membrane Camouflaged Au Nanoshells for in Vivo Prolonged
      Circulation Life and Enhanced Cancer Photothermal Therapy.
AB  - Macrophage cell membrane (MPCM)-camouflaged gold nanoshells (AuNS) that can serve
      as a new generation of photothermal conversion agents for in vivo photothermal
      cancer therapy are presented. They are constructed by the fusion of biocompatible
      AuNSs and MPCM vesicles. The resulting MPCM-coated AuNSs exhibited good colloidal
      stability and kept the original near-infrared (NIR) adsorption of AuNSs. Because
      AuNS carried high-density coverage of MPCMs, the totally functional portions of
      macrophage cells membrane were grafted onto the surface of AuNSs. This surface
      functionalization provided active targeting ability by recognizing tumor
      endothelium and thus improved tumoritropic accumulation compared to the red blood
      cell membrane-coating approach. These biomimetic nanoparticles significantly
      enhance in vivo blood circulation time and local accumulation at the tumor when
      administered systematically. Upon NIR laser irradiation, local heat generated by
      the MPCM-coated AuNS achieves high efficiency to suppress tumor growth and
      selectively ablate cancerous cells within the illuminated zone. Therefore, MPCM
      coated AuNSs remained the natural properties of their source cells, which may
      improve the efficacy of photothermal therapy modulated by AuNSs and other noble
      metal nanoparticles. 

PMID- 27039689
TI  - Management of Male Reproductive Tract Injuries and Disease.
AB  - Medical and surgical management can be used to restore a bull that has suffered a
      reproductive tract malady. The economic cost of treatment weighed against the
      bull's replacement value as well as prognosis for recovery is of prime
      consideration. In turn, early recognition of a treatable condition and immediate
      initiation of action are factors that impact both treatment cost and prognosis in
      many cases. Common problems are penile hair rings, fibropapillomas, vesicular
      adenitis, penile hematoma, and traumatic injury to the prepuce. Less frequent
      problems are injuries that lead to denervation of the penis, penile shunts, and
      penile deviation. 

PMID- 27039690
TI  - Evaluating Information Obtained from Diagnosis of Pregnancy Status of Beef Herds.
AB  - Good reproductive efficiency is critical for economic sustainability of beef
      herds. Standard measurements of reproductive success are the percentage of cows
      exposed to bulls at the start of the breeding season that are pregnant at
      midgestation and the percentage of pregnant cows that give birth to a live calf.
      Converting fetal age data to a reproductive profile displaying pregnancy
      percentages by 21-day periods provides information for the diagnosis of
      suboptimal reproductive efficiency and guides intervention strategies. The value
      can be amplified by evaluating reproductive profiles by animal age or management
      group. 

PMID- 27039691
TI  - Management and Breeding Soundness of Mature Bulls.
AB  - Mature bulls must be fed a balanced ration, vaccinated appropriately, and undergo
      a breeding soundness evaluation to ensure they meet what is required of a short,
      but intense breeding season. To be classified as a satisfactory potential
      breeder, minimum standards for physical soundness, scrotal circumference, sperm
      motility, and sperm morphology must be achieved using an accepted bull-breeding
      soundness evaluation format. Sperm production requires approximately 70 days.
      Heat and stress are the most common insults to spermatogenesis, causing an
      increase in morphologic abnormalities with obesity-associated scrotal fat
      accumulation being the most frequent cause of elevated testicular temperature in
      mature bulls. 

PMID- 27039692
TI  - Tritrichomonas foetus Prevention and Control in Cattle.
AB  - Bovine trichomoniasis has been recognized as a pathogen of the bovine
      reproductive tract for nearly 100 years. Although characteristics of the
      causative organism, Tritrichomonas foetus lend to control and there are examples
      of disease eradication, cattle producers are still faced with this disease. This
      article highlights the clinical presentation, magnitude of effect, risk factors,
      epidemiology, and sample collection and suggests applications in developing herd
      level control measures for beef cattle producers including testing strategies for
      control, testing strategies for surveillance, strategies to eliminate
      trichomoniasis from infected herds, and strategies for prevention in uninfected
      herds. 

PMID- 27039693
TI  - Synchronization and Artificial Insemination Strategies in Dairy Herds.
AB  - Timed artificial insemination (AI) programs are commonly used in the dairy
      industry for lactating cows, but less so in replacement heifers. Excellent
      programs using combinations of prostaglandin F2alpha and gonadotropin-releasing
      hormone in protocols relying on timed AI without detection of estrus or in
      protocols that combine timed AI with inseminations performed after detected
      estrus are able to achieve acceptable pregnancy percentages. In herds with
      excellent estrus detection, timed AI programs serve as a failsafe system to
      address cows or heifers not yet inseminated after a defined period of estrus
      detection. 

PMID- 27039694
TI  - Beef Heifer Development.

PMID- 27039695
TI  - What can we learn from a case report? It's not always about the Swiss cheese.

PMID- 27039696
TI  - Sample-poor estimation of order and common signal subspace with application to
      fusion of medical imaging data.
AB  - Due to their data-driven nature, multivariate methods such as canonical
      correlation analysis (CCA) have proven very useful for fusion of multimodal
      neurological data. However, being able to determine the degree of similarity
      between datasets and appropriate order selection are crucial to the success of
      such techniques. The standard methods for calculating the order of multimodal
      data focus only on sources with the greatest individual energy and ignore
      relations across datasets. Additionally, these techniques as well as the most
      widely-used methods for determining the degree of similarity between datasets
      assume sufficient sample support and are not effective in the sample-poor regime.
      In this paper, we propose to jointly estimate the degree of similarity between
      datasets and their order when few samples are present using principal component
      analysis and canonical correlation analysis (PCA-CCA). By considering these two
      problems simultaneously, we are able to minimize the assumptions placed on the
      data and achieve superior performance in the sample-poor regime compared to
      traditional techniques. We apply PCA-CCA to the pairwise combinations of
      functional magnetic resonance imaging (fMRI), structural magnetic resonance
      imaging (sMRI), and electroencephalogram (EEG) data drawn from patients with
      schizophrenia and healthy controls while performing an auditory oddball task. The
      PCA-CCA results indicate that the fMRI and sMRI datasets are the most similar,
      whereas the sMRI and EEG datasets share the least similarity. We also demonstrate
      that the degree of similarity obtained by PCA-CCA is highly predictive of the
      degree of significance found for components generated using CCA.

PMID- 27039697
TI  - Modulating rest-break length induces differential recruitment of automatic and
      controlled attentional processes upon task reengagement.
AB  - Rest breaks are commonly administered as a countermeasure to reduce on-the-job
      fatigue, both physical and mental. However, this practice makes the assumption
      that recovery from fatigue, as measured by the reversal of performance declines,
      is the sole effect of taking a break on behavior. Here, through administering
      rest breaks of differing lengths in between blocks of a mentally demanding symbol
      decoding task, we show that this assumption may not be strictly true. First, we
      replicate previous work by showing that taking a longer break leads to two
      correlated effects: greater immediate rebound in performance, and greater
      subsequent time-on-task decline. Using fMRI, we reveal that time-on-task in this
      paradigm is associated with increasing recruitment of fronto-parietal areas
      associated with top-down control, and decreasing deactivation in the default-mode
      network. Finally, by analyzing individual differences, we reveal a potential
      neural basis for our behavioral observation: greater recovery following long
      breaks is associated with greater activity in the putamen, an area associated
      with the automatic generation of motor responses, followed by greater activity in
      left middle frontal gyrus by the end of those task periods. Taken together, this
      suggests a shift in the implicit engagement of automatic and controlled
      attentional processing following longer breaks. This shift may be undesirable or
      detrimental in real-world situations where maintaining a stable level of
      attention over time is necessary.

PMID- 27039698
TI  - Using neuroimaging to help predict the onset of psychosis.
AB  - The aim of this review is to assess the potential for neuroimaging measures to
      facilitate prediction of the onset of psychosis. Research in this field has
      mainly involved people at 'ultra-high risk' (UHR) of psychosis, who have a very
      high risk of developing a psychotic disorder within a few years of presentation
      to mental health services. The review details the key findings and developments
      in this area to date and examines the methodological and logistical challenges
      associated with making predictions in an individual subject in a clinical
      setting.

PMID- 27039699
TI  - A biophysical model of brain deformation to simulate and analyze longitudinal
      MRIs of patients with Alzheimer's disease.
AB  - We propose a framework for developing a comprehensive biophysical model that
      could predict and simulate realistic longitudinal MRIs of patients with
      Alzheimer's disease (AD). The framework includes three major building blocks: i)
      atrophy generation, ii) brain deformation, and iii) realistic MRI generation.
      Within this framework, this paper focuses on a detailed implementation of the
      brain deformation block with a carefully designed biomechanics-based tissue loss
      model. For a given baseline brain MRI, the model yields a deformation field
      imposing the desired atrophy at each voxel of the brain parenchyma while allowing
      the CSF to expand as required to globally compensate for the locally prescribed
      volume loss. Our approach is inspired by biomechanical principles and involves a
      system of equations similar to Stokes equations in fluid mechanics but with the
      presence of a non-zero mass source term. We use this model to simulate
      longitudinal MRIs by prescribing complex patterns of atrophy. We present
      experiments that provide an insight into the role of different biomechanical
      parameters in the model. The model allows simulating images with exactly the same
      tissue atrophy but with different underlying deformation fields in the image. We
      explore the influence of different spatial distributions of atrophy on the image
      appearance and on the measurements of atrophy reported by various global and
      local atrophy estimation algorithms. We also present a pipeline that allows
      evaluating atrophy estimation algorithms by simulating longitudinal MRIs from
      large number of real subject MRIs with complex subject-specific atrophy patterns.
      The proposed framework could help understand the implications of different model
      assumptions, regularization choices, and spatial priors for the detection and
      measurement of brain atrophy from longitudinal brain MRIs.

PMID- 27039701
TI  - Sex differences in the functional connectivity of the amygdalae in association
      with cortisol.
AB  - Human amygdalae are involved in various behavioral functions such as affective
      and stress processing. For these behavioral functions, as well as for
      psychophysiological arousal including cortisol release, sex differences are
      reported. Here, we assessed cortisol levels and resting-state functional
      connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42
      women) to investigate potential modulation of amygdala rsFC by sex and cortisol
      concentration. Our analyses revealed that rsFC of the left amygdala significantly
      differed between women and men: Women showed stronger rsFC than men between the
      left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral
      gyrus and hippocampus, regions involved in face processing, inner-speech, fear
      and pain processing. No stronger connections were detected for men and no sex
      difference emerged for right amygdala rsFC. Also, an interaction of sex and
      cortisol appeared: In women, cortisol was negatively associated with rsFC of the
      amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate
      gyrus, middle and superior frontal gyri, supplementary motor area and the
      parietal-occipital sulcus. Contrarily in men, positive associations of cortisol
      with rsFC of the left amygdala and these structures were observed. Functional
      decoding analyses revealed an association of the amygdalae and these regions with
      emotion, reward and memory processing, as well as action execution. Our results
      suggest that functional connectivity of the amygdalae as well as the regulatory
      effect of cortisol on brain networks differs between women and men. These sex
      differences and the mediating and sex-dependent effect of cortisol on brain
      communication systems should be taken into account in affective and stress
      related neuroimaging research. Thus, more studies including both sexes are
      required.

PMID- 27039700
TI  - Power estimation for non-standardized multisite studies.
AB  - A concern for researchers planning multisite studies is that scanner and T1
      weighted sequence-related biases on regional volumes could overshadow true
      effects, especially for studies with a heterogeneous set of scanners and
      sequences. Current approaches attempt to harmonize data by standardizing
      hardware, pulse sequences, and protocols, or by calibrating across sites using
      phantom-based corrections to ensure the same raw image intensities. We propose to
      avoid harmonization and phantom-based correction entirely. We hypothesized that
      the bias of estimated regional volumes is scaled between sites due to the
      contrast and gradient distortion differences between scanners and sequences.
      Given this assumption, we provide a new statistical framework and derive a power
      equation to define inclusion criteria for a set of sites based on the variability
      of their scaling factors. We estimated the scaling factors of 20 scanners with
      heterogeneous hardware and sequence parameters by scanning a single set of 12
      subjects at sites across the United States and Europe. Regional volumes and their
      scaling factors were estimated for each site using Freesurfer's segmentation
      algorithm and ordinary least squares, respectively. The scaling factors were
      validated by comparing the theoretical and simulated power curves, performing a
      leave-one-out calibration of regional volumes, and evaluating the absolute
      agreement of all regional volumes between sites before and after calibration.
      Using our derived power equation, we were able to define the conditions under
      which harmonization is not necessary to achieve 80% power. This approach can
      inform choice of processing pipelines and outcome metrics for multisite studies
      based on scaling factor variability across sites, enabling collaboration between
      clinical and research institutions.

PMID- 27039702
TI  - An a contrario approach for the detection of patient-specific brain perfusion
      abnormalities with arterial spin labelling.
AB  - In this paper, we introduce a new locally multivariate procedure to
      quantitatively extract voxel-wise patterns of abnormal perfusion in individual
      patients. This a contrario approach uses a multivariate metric from the computer
      vision community that is suitable to detect abnormalities even in the presence of
      closeby hypo- and hyper-perfusions. This method takes into account local
      information without applying Gaussian smoothing to the data. Furthermore, to
      improve on the standard a contrario approach, which assumes white noise, we
      introduce an updated a contrario approach that takes into account the spatial
      coherency of the noise in the probability estimation. Validation is undertaken on
      a dataset of 25 patients diagnosed with brain tumours and 61 healthy volunteers.
      We show how the a contrario approach outperforms the massively univariate general
      linear model usually employed for this type of analysis.

PMID- 27039703
TI  - Dynamics of scene representations in the human brain revealed by
      magnetoencephalography and deep neural networks.
AB  - Human scene recognition is a rapid multistep process evolving over time from
      single scene image to spatial layout processing. We used multivariate pattern
      analyses on magnetoencephalography (MEG) data to unravel the time course of this
      cortical process. Following an early signal for lower-level visual analysis of
      single scenes at ~100ms, we found a marker of real-world scene size, i.e. spatial
      layout processing, at ~250ms indexing neural representations robust to changes in
      unrelated scene properties and viewing conditions. For a quantitative model of
      how scene size representations may arise in the brain, we compared MEG data to a
      deep neural network model trained on scene classification. Representations of
      scene size emerged intrinsically in the model, and resolved emerging neural scene
      size representation. Together our data provide a first description of an
      electrophysiological signal for layout processing in humans, and suggest that
      deep neural networks are a promising framework to investigate how spatial layout
      representations emerge in the human brain.

PMID- 27039704
TI  - Use of a steady-state baseline to address evoked vs. oscillation models of visual
      evoked potential origin.
AB  - There has been a long debate about the neural mechanism of event-related
      potentials (ERPs). Previously, no evidence or method was apparent to validate the
      two competing models, the evoked model and the oscillation model. One argument is
      whether the pre-stimulus brain oscillation could influence the following ERP.
      This study carried out an innovative visual oddball task experiment to
      investigate the dynamic process of visual evoked potentials. A period of stable
      oscillations of specified dominant frequencies and initial phases, i.e. the
      steady-state baseline, would be induced before responses to transient stimuli of
      different contrasts, which could overcome the artifact problem caused by the
      'sorting' method. The result first revealed a 'three-period-transition' for the
      generation of visual evoked potentials by an objective decomposition. The ERP
      almost retained the preceding oscillation during the first period, provided an
      unstable negative potential in the second period, and generated the N1 component
      in the third period. The cross term analysis showed that the evoked model
      couldn't be the whole explanation for the ERP generation. Furthermore, the
      component analysis revealed that the N1 latency was sensitive to the initial
      phase under the low stimulus contrast (supporting the oscillation model) but not
      under the high stimulus contrast (supporting the evoked model). It demonstrated
      that the external stimulus contrast is a significant factor deciding the explicit
      model for ERPs. Our method and preliminary results may help reconcile the
      previous, seemly contradictory findings on the ERP mechanism.

PMID- 27039705
TI  - Physiological processes non-linearly affect electrophysiological recordings
      during transcranial electric stimulation.
AB  - Transcranial electric stimulation (tES) is a promising tool to non-invasively
      manipulate neuronal activity in the human brain. Several studies have shown
      behavioral effects of tES, but stimulation artifacts complicate the simultaneous
      investigation of neural activity with EEG or MEG. Here, we first show for EEG and
      MEG, that contrary to previous assumptions, artifacts do not simply reflect
      stimulation currents, but that heartbeat and respiration non-linearly modulate
      stimulation artifacts. These modulations occur irrespective of the stimulation
      frequency, i.e. during both transcranial alternating and direct current
      stimulations (tACS and tDCS). Second, we show that, although at first sight
      previously employed artifact rejection methods may seem to remove artifacts, data
      are still contaminated by non-linear stimulation artifacts. Because of their
      complex nature and dependence on the subjects' physiological state, these
      artifacts are prone to be mistaken as neural entrainment. In sum, our results
      uncover non-linear tES artifacts, show that current techniques fail to fully
      remove them, and pave the way for new artifact rejection methods. 

PMID- 27039707
TI  - Small molecules, both dietary and endogenous, influence the onset of lens
      cataracts.
AB  - How the lens ages successfully is a lesson in biological adaption and the
      emergent properties of its complement of cells and proteins. This living tissue
      contains some of the oldest proteins in our bodies and yet they remain functional
      for decades, despite exposure to UV light, to reactive oxygen species and all the
      other hazards to protein function. This remarkable feat is achieved by a shrewd
      investment in very stable proteins as lens crystallins, by providing a reservoir
      of ATP-independent protein chaperones unequalled by any other tissue and by an
      oxidation-resistant environment. In addition, glutathione, a free radical
      scavenger, is present in mM concentrations and the plasma membranes contain
      oxidation-resistant sphingolipids what compromises lens function as it ages? In
      this review, we examine the role of small molecules in the prevention or
      causation of cataracts, including those associated with diet, metabolic pathways
      and drug therapy (steroids).

PMID- 27039708
TI  - Intracerebroventricular gene therapy that delays neurological disease progression
      is associated with selective preservation of retinal ganglion cells in a canine
      model of CLN2 disease.
AB  - CLN2 disease is one of a group of lysosomal storage disorders called the neuronal
      ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene
      that cause an insufficiency or complete lack of the soluble lysosomal enzyme
      tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein
      degradation, and lack of this enzyme results in the accumulation of protein-rich
      autofluorescent lysosomal storage bodies in numerous cell types including neurons
      throughout the central nervous system and the retina. CLN2 disease is
      characterized primarily by progressive loss of neurological functions and vision
      as well as generalized neurodegeneration and retinal degeneration. In children
      the progressive loss of neurological functions typically results in death by the
      early teenage years. A Dachshund model of CLN2 disease with a null mutation in
      TPP1 closely recapitulates the human disorder with a progression from disease
      onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of
      functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of
      the recombinant protein or by a single administration of a TPP1 gene therapy
      vector to the CSF, significantly delays the onset and progression of neurological
      signs and prolongs life span but does not prevent the loss of vision or modest
      retinal degeneration that occurs by 11 months of age. In this study we found that
      in dogs that received the CSF gene therapy treatment, the degeneration of the
      retina and loss of retinal function continued to progress during the prolonged
      life spans of the treated dogs. Eventually the normal cell layers of the retina
      almost completely disappeared. An exception was the ganglion cell layer. In
      affected dogs that received TPP1 gene therapy to the CSF and survived an average
      of 80 weeks, ganglion cell axons were present in numbers comparable to those of
      normal Dachshunds of similar age. The selective preservation of the retinal
      ganglion cells suggests that while TPP1 protein delivered via the CSF may protect
      these cells, preservation of the remainder of the retina will require delivery of
      normal TPP1 more directly to the retina, probably via the vitreous body.

PMID- 27039709
TI  - Paracoccus yeei peritonitis in peritoneal dialysis.

PMID- 27039710
TI  - Cd(ii)-MOF-IM: post-synthesis functionalization of a Cd(ii)-MOF as a triphase
      transfer catalyst.
AB  - A robust and porous Cd(ii)-MOF based on a bent imidazole-bridged ligand was
      synthesized and post-synthetically functionalized with linear alkyl chains to
      afford imidazolium salt (IM)-type triphase transfer catalysts for organic
      transformations. The imidazolium salt decorated Cd(ii)-MOF-IM exhibits typical
      solid phase transfer catalytic behavior for the azidation and thiolation of
      bromoalkane between aqueous/organic phases. Moreover, they can be easily
      recovered and reused under the PTC conditions. Cd(ii)-MOF-IM herein created a
      versatile family of solid phase transfer catalysts for promoting a broad scope of
      reactions carried out in a biphasic mixture of two immiscible solvents. 

PMID- 27039711
TI  - Electrically controllable terahertz square-loop metamaterial based on VO2 thin
      film.
AB  - An electrically controllable square-loop metamaterial based on vanadium dioxide
      (VO2) thin film was proposed in the terahertz frequency regime. The square-loop
      shaped metamaterial was adopted to perform roles not only as a resonator but also
      as a micro-heater for the electrical control of the VO2. A dual-resonant square
      loop structure was designed to realize band-pass characteristics in the desired
      frequency band. The measured Q-factors of the basic and scaled-down metamaterials
      fabricated on VO2 thin films were 2.22 and 1.61 at the center frequencies of 0.44
      and 1.14 THz in the passbands, respectively. The transmittances of the proposed
      metamaterial were successfully controlled by applying a bias voltage without an
      external heater. The measured transmittance on-off ratios of the metamaterials
      were over 40 at the center frequencies in the passbands. In the future,
      electrically controllable terahertz metamaterial based on VO2 metamaterial could
      be employed as high-performance active filters or sensors. 

PMID- 27039712
TI  - NAB2-STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary
      fibrous tumors: the association between fusion variants and locations.
AB  - Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm harboring NAB2-STAT6
      fusion, which drives STAT6 nuclear relocation. For extrathoracic SFTs, the
      clinical relevance of this molecular hallmark remains obscure. We assessed STAT6
      immunoexpression for 61 extrathoracic SFTs exclusive of the meninges and head and
      neck, and 25 had analyzable RNAs to distinguish fusion variants by RT-PCR. The
      immunohistochemical and molecular findings were correlated with
      clincopathological features and disease-free survival (DFS). Twenty-eight males
      and 33 females had SFTs in the body cavities (n = 31), extremities (n = 17), and
      trunk (n = 13), categorized into 53 non-malignant and 8 malignant tumors. The
      vast majority (n = 57, 93%) exhibited distinctive STAT6 nuclear expression,
      including malignant ones. The common fusion variants were NAB2ex6-STAT6ex16/17 in
      13 SFTs and NAB2ex4-STAT6ex2 in 8, while miscellaneous variants were detected
      only in 4 SFTs in the limbs and trunk but not in any body cavity-based cases (P =
      0.026). The worse DFS was univariately associated with malignant histology (P =
      0.04) but unrelated to tumor size, location, or fusion variant. Conclusively,
      extrathoracic SFTs mostly harbor NAB2ex6-STAT6ex16/17, followed by NAB2ex4
      STAT6ex2. Miscellaneous variants are significantly rare in SFTs within the body
      cavities. The clinical aggressiveness of extrathoraic SFTs is associated with
      malignant histology but unrelated to the NAB2-STAT6 fusion variants. 

PMID- 27039713
TI  - General practitioners' experiences as nursing home medical consultants.
AB  - OBJECTIVE: To describe general practitioners' experiences of being the principal
      physician responsible for a nursing home. METHOD: Fifteen general practitioners
      assigned to a nursing home participated in semi-structured qualitative
      interviews. Data were analysed using systematic text condensation. RESULT:
      Medical assessment is the main duty of general practitioners. Advance care
      planning together with residents and family members facilitates future decisions
      on medical treatment and end-of-life care. Registered Nurses' continuity and
      competence are perceived as crucial to the quality of care, but inadequate
      staffing, lack of medical equipment and less-than-optimal IT systems for
      electronic healthcare records are impediments to patient safety. CONCLUSION: The
      study highlights the importance of advance care planning together with residents
      and family members in facilitating future decisions on medical treatment and end
      of-life care. To meet the increasing demands for more complex medical treatment
      at nursing homes and to provide high-quality palliative care, there would seem to
      be a need to increase Registered Nurses' staffing and acquire more advanced
      medical equipment, as well as to create better possibilities for Registered
      Nurses and general practitioners to access each other's healthcare record
      systems.

PMID- 27039714
TI  - Microchips and their Significance in Isolation of Circulating Tumor Cells and
      Monitoring of Cancers.
AB  - In micro-fluid systems, fluids are injected into extremely narrow polymer
      channels in small amounts such as micro-, nano-, or pico-liter scales. These
      channels themselves are embedded on tiny chips. Various specialized structures in
      the chips including pumps, valves, and channels allow the chips to accept
      different types of fluids to be entered the channel and along with flowing
      through the channels, exert their effects in the framework of different
      reactions. The chips are generally crystal, silicon, or elastomer in texture.
      These highly organized structures are equipped with discharging channels through
      which products as well as wastes of the reactions are secreted out. A particular
      advantage regarding the use of fluids in micro-scales over macro-scales lies in
      the fact that these fluids are much better processed in the chips when they
      applied as micro-scales. When the laboratory is miniaturized as a microchip and
      solutions are injected on a micro-scale, this combination makes a specialized
      construction referred to as "lab-on-chip". Taken together, micro-fluids are among
      the novel technologies which further than declining the costs; enhancing the test
      repeatability, sensitivity, accuracy, and speed; are emerged as widespread
      technology in laboratory diagnosis. They can be utilized for monitoring a wide
      spectrum of biological disorders including different types of cancers. When these
      microchips are used for cancer monitoring, circulatory tumor cells play a
      fundamental role. 

PMID- 27039715
TI  - Preventive and Risk Reduction Strategies for Women at High Risk of Developing
      Breast Cancer: a Review.
AB  - Breast cancer is the most commonly diagnosed invasive cancer among women. Many
      factors, both genetic and non-genetic, determine a woman's risk of developing
      breast cancer and several breast cancer risk prediction models have been
      proposed. It is vitally important to risk stratify patients as there are now
      effective preventive strategies available. All women need to be counseled
      regarding healthy lifestyle recommendations to decrease breast cancer risk. As
      such, management of these women requires healthcare professionals to be familiar
      with additional risk factors so that timely recommendations can be made on
      surveillance/risk-reducing strategies. Breast cancer risk reduction strategies
      can be better understood by encouraging the women at risk to participate in
      clinical trials to test new strategies for decreasing the risk. This article
      reviews the advances in the identification of women at high risk of developing
      breast cancer and also reviews the strategies available for breast cancer
      prevention. 

PMID- 27039716
TI  - Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer.
AB  - Breast cancer is one of the major threats to female health, and its incidence is
      rapidly increasing in many countries. Currently, breast cancer is treated with
      surgery, followed by chemotherapy or radiation therapy, or both. However, a
      substantial proportion of breast cancer patients might have a risk for local
      relapse that leads to recurrence of their disease and/or metastatic breast
      cancer. Therefore searching for new and potential strategies for breast cancer
      treatment remains necessary. Immunotherapy is an attractive and promising
      approach that can exploit the ability of the immune system to identify and
      destroy tumors and thus prevent recurrence and metastatic lesions. The most
      promising and attractive approach of immunotherapeutic research in cancer is the
      blockade of immune checkpoints. In this review, we discuss the potential of
      certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic
      T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte
      activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint
      inhibitors may represent future standards of care for breast cancer as
      monotherapy or combined with standard therapies. 

PMID- 27039717
TI  - Integrated Bioinformatics Approach Reveals Crosstalk Between Tumor Stroma and
      Peripheral Blood Mononuclear Cells in Breast Cancer.
AB  - Breast cancer is now the leading cause of cancer death in women worldwide. Cancer
      progression is driven not only by cancer cell intrinsic alterations and
      interactions with tumor microenvironment, but also by systemic effects.
      Integration of multiple profiling data may provide insights into the underlying
      molecular mechanisms of complex systemic processes. We performed a bioinformatic
      analysis of two public available microarray datasets for breast tumor stroma and
      peripheral blood mononuclear cells, featuring integrated transcriptomics data,
      protein-protein interactions (PPIs) and protein subcellular localization, to
      identify genes and biological pathways that contribute to dialogue between tumor
      stroma and the peripheral circulation. Genes of the integrin family as well as
      CXCR4 proved to be hub nodes of the crosstalk network and may play an important
      role in response to stroma-derived chemoattractants. This study pointed to
      potential for development of therapeutic strategies that target systemic signals
      travelling through the circulation and interdict tumor cell recruitment. 

PMID- 27039718
TI  - Effects of TNFalpha, NOS3, MDR1 Gene Polymorphisms on Clinical Parameters,
      Prognosis and Survival of Multiple Myeloma Cases.
AB  - It is not clear how gene polymorphisms affecting drugs can contributes totheir
      efficacy in multiple myeloma (MM). We here aimed to explore associations among
      gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide
      synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters,
      prognosis and survival in MM patients treated with VAD (vincristine-adriamycine
      dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation
      (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide
      dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and
      77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There
      was no clinically significant difference between MM and control groups when TNF
      alpha(-238) and (-857) and MDR1 gene polymorphisms were studied. However, the
      TNFalphagene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT
      genotype (p=0.008) were more common in the MM group compared to healthy controls.
      NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in
      the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNF alpha(-308)
      GG genotypes may have roles in myeloma pathogenesis. 

PMID- 27039719
TI  - Correlations between HER2 Expression and Other Prognostic Factors in Breast
      Cancer: Inverse Relations with the Ki-67 Index and P53 Status.
AB  - BACKGROUND: Overexpression or amplification of human epidermal growth factor
      receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in
      breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a
      prognostic marker, and to analyze associations with common histopathological
      parameters in BC cases. MATERIALS AND METHODS: Between of 2007 to 2014, 260
      patients with BC referred to Oncology Clinic provided cancer tissue samples which
      underwent immunohistochemistry (IHC) for markers. ER and PR positivity was
      defined as >=10% positive tumor cells with nuclear staining. HER2-positive was
      defined as either HER2 gene amplification by fluorescent in situ hybridization
      (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine
      HER2 positivity. RESULTS: The mean age at diagnosis for the patients with HER2
      negative was significantly higher than in HER2-positive cases. Also, there were
      significant correlations between histological grade, nuclear grade, lymph node
      metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index
      with HER2 expression. HER2-negative lesions were of higher grade and more likely
      to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor
      size<2cm and also Ki-67>=20% as compared to the HER2-positive group. CONCLUSIONS:
      Contrary to the results of other studies, HER2-positive tumors in our study had a
      lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index >=20% in
      more studies was associated with p53-positive.Therefore, tumors which are HER2
      positive and have a Ki-67>=20% had a more aggressive behavior compared to HER2
      positive and Ki-67<20% lesions.

PMID- 27039720
TI  - Proactive Consultation by a Clinical Pathologist Prevents Diagnostic Delay in
      Hematological Malignancies.
AB  - BACKGROUND: Diagnostic difficulties in hematological malignancies may lead to
      unacceptably prolonged help-seeking to diagnostic interval as well as increased
      complications and poor outcomes. Proactive consultation by a clinical pathologist
      (PCCP) may help clinical diagnosis and therapeutic strategy. Hence, the aim of
      this investigation was to evaluate the effect of PCCP on the help-seeking to
      diagnostic interval in hematological cancer cases. MATERIALS AND METHODS: From
      January to November, 2015, abnormal results of hematological laboratory testing
      with added laboratory comment were selectively screened out, and patients with
      such abnormalities in hematological laboratory testing and accompanied laboratory
      comment with PCCP were enrolled. RESULTS: A total of 125 aberrant results of
      hematological laboratory testing were given with accompanied laboratory comments
      with PCCP and 40.8% (n=51) of these patient-oriented comments had an effect on
      clinical diagnosis and therapeutic strategy. Twelve of the subjects belonged to
      newly diagnosed hematological malignancies with the assistance of PCCP, and the
      help-seeking to diagnostic interval was also shortened from 42 days to 26 days in
      chronic lymphoid leukemia (CLL), from 83 days to 11 days in multiple myeloma
      (MM), and from 128 days to 15 days in myelodysplastic syndrome/myeloproliferative
      neoplasm (MDS/MPN). During the monitoring interval, neither complication events
      nor deaths were reported in the study group. CONCLUSIONS: It was seemingly that
      PCCP prevented diagnostic delay in hematological malignancies via shortening the
      help-seeking to diagnostic interval, particularly in CLL, MM and MDS/MPN cases.
      PCCP can be considered to play an essential role in prompt establishment of
      diagnosis in hematological malignancies for those who newly present.

PMID- 27039721
TI  - Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy
      in Multistep Rat Colon Carcinogenesis Bioassays.
AB  - The purpose of this study was to investigate the role of colon cancer stem cells
      (CSCs) during chemicallyinduced rat multi-step colon carcinogenesis with or
      without the treatment with a specific cyclooxygenase-2 inhibitor drug
      (celecoxib). Two experiments were performed, the first, a short term 12 week
      colon carcinogenesis bioassay in which only surrogate markers for colon cancer,
      aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium
      term colon cancer rat assay in which tumors had developed after 32 weeks.
      Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes
      and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear
      antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by
      celecoxib. Also different cell surface antigens known to associate with CSCs such
      as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared
      between the two experiments and showed differential expression patterns depending
      on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric
      analysis demonstrated that the numbers of CD133 cells were increased in the
      colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were
      increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in
      the colonic epithelium (a known CSC marker) detected by ELISA assay were found
      down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data
      have also shown that the protective effect of celecoxib on these specific markers
      and populations of CSCs and on other molecular processes such as apoptosis
      targeted by this drug may vary depending on the genetic and phenotypic stages of
      carcinogenesis. Therefore, uncovering these distinction roles of CSCs during
      different phases of carcinogenesis and during specific treatment could be useful
      for targeted therapy. 

PMID- 27039722
TI  - HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases
      Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition
      Genes.
AB  - HOX transcription factors are evolutionarily conserved in many different species
      and are involved in important cellular processes such as morphogenesis,
      differentiation, and proliferation. They have also recently been implicated in
      carcinogenesis, but their precise role in cancer, especially in cervical cancer
      (CC), remains unclear. In this work, using microarray assays followed by the
      quantitative polymerase chain reaction (qPCR), we found that the expression of 25
      HOX genes was downregulated in CC derived cell lines compared with nontumorigenic
      keratinocytes. In particular, the expression of HOXA9 was observed as down
      modulated in CCderived cell lines. The expression of HOXA9 has not been
      previously reported in CC, or in normal keratinocytes of the cervix. We found
      that normal CC from women without cervical lesions express HOXA9; in contrast, CC
      cell lines and samples of biopsies from women with CC showed significantly
      diminished HOXA9 expression. Furthermore, we found that methylation at the first
      exon of HOXA9 could play an important role in modulating the expression of this
      gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell
      proliferation and migration, and induced an epithelial-like phenotype.
      Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes
      induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears
      to be a necessary step during CC development. Further studies are needed to
      delineate the role of HOXA9 during malignant progression and to afford more
      insights into the relationship between downmodulation of HOXA9 and viral HPV
      oncoprotein expression during cercical cancer development. 

PMID- 27039723
TI  - Spectrum of the WHO Classification De Novo Myelodysplastic Syndrome: Experience
      from Southern Pakistan.
AB  - BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disorder of hemopoeitic
      stem cells, characterized by infective hematopoiesis, peripheral cytopenias along
      with hypercellularity of marrow and marked dysplastic features. Our aim was to
      study the spectrum of the WHO classification in adult Pakistani patients with MDS
      at disease presentation. MATERIALS AND METHODS: This retrospective descriptive
      study was conducted at Liaquat National Hospital and Medical College, extending
      from January 2010 to December 2014. Patient data were retrieved from the
      maintained archives. RESULTS: Overall, 45 patients were diagnosed at our
      institution with de novo MDS during the study period. There were 28 males and 17
      females. Age ranged between 18 and 95 years with a mean of 57.6+/-17.4 years. The
      male to female ratio was 1.7:1. According to the WHO classification, 53.3% had
      refractory cytopenia with multilineage dysplasia, 22.2% had refractory cytopenia
      with unilineage dysplasia, 4.4% each had refractory anemia with excess of blasts
      1 and II and 15.5% had MDS unclassified. The main presenting complaints were
      generalized fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and
      weight loss (11.1%). Physical examination revealed pallor in 37.7%, followed by
      petechial and purpuric rashes in 20% of patients. Hemoglobin was <10 g/dl in 41
      (91.1%). Pancytopenia and bicytopenia were noted in 18 (40%) and 14 (31.1%)
      respectively. CONCLUSIONS: MDS in our patients presents at a relatively young
      age. Refractory c ytopenia with multilineage dysplasia was the dominant disease
      variant in our setting.

PMID- 27039724
TI  - Somatic JAK-2 V617F Mutational Analysis in Polycythemia Rubra Vera: a Tertiary
      Care Center Experience.
AB  - BACKGROUND: Polycythemia rubra vera (PV), being a primary polycythemia, is caused
      by neoplastic proliferation of erythroid, megakaryocytic and granulocytic
      lineages which result in panmyelosis. PV patients have a somatic acquired
      mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation
      independent of the normal regulatory mechanisms that regulate erythropoiesis. The
      rational of this study was to determine the prevalence of the JAK-2 V617F
      mutation in Pakistani patients with PV. MATERIALS AND METHODS: In this cross
      sectional study, 26 patients with PV were enrolled from January 2010 to December
      2014. Patients were diagnosed based on WHO criteria for PV. All were screened for
      G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific
      PCR. RESULTS: The mean age was 53.4+/-9.31 years (range 36-72) and the male to
      female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients
      was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining
      69.3% presented with symptomatic disease. The mean hemoglobin was 18.1+/-1.9g/dl
      with the mean hematocrit of 55.6+/-8.3%. The mean total leukocyte count was
      12.8+/-7.1x109/l and the platelet count was 511+/-341.9x109/l. A positive
      correlation of JAK2 V617F mutation was established with high TLC count (P=0.01).
      No correlation of JAK2 V617F could be established with age or gender (P>0.05).
      CONCLUSIONS: The JAK2 V617F mutation frequency in our PV patients was similar to
      those reported internationally. Screening for the mutation in all suspected PV
      cases could be beneficial in differentiating patients with reactive and clonal
      erythrocytosis.

PMID- 27039725
TI  - Role of the Mdm2 SNIP 309 Polymorphism in Gastric Mucosal Morphologic Patterns of
      Patients with Helicobacter pylori Associated Gastritis.
AB  - BACKGROUND: The tumor suppressor p53 is as a regulator of cell proliferation,
      apoptosis and many other biological processes as well as external and internal
      stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this
      study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the
      gastric mucosal morphological patterns in patients with Helicobacter pylori
      associated gastritis. MATERIALS AND METHODS: A prospective cross-sectional study
      was carried out from November 2014 through November 2015. Biopsy specimens were
      obtained from patients and infection was proven by positive histology. Gastric
      mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine,
      Suranaree University of Technology where they were tested by molecular methods to
      detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR
      hybridization probe method. The results were analyzed and correlated with gastric
      mucosal morphological patterns by using C-NBI endoscopy. RESULTS: A total of 300
      infected patients were enrolled and gastric mucosa specimens were collected. In
      this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T
      heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous
      was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity
      correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01)
      whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01).
      CONCLUSIONS: Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai
      population is very low, and suggests that this can explain ae Thailand enigma.
      Types 1 to type 3 are the most common gastric mucosal morphological patterns
      according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai
      population.

PMID- 27039726
TI  - Commonest Cancers in Pakistan - Findings and Histopathological Perspective from a
      Premier Surgical Pathology Center in Pakistan.
AB  - CONTEXT: There are no recent authoritative data about incidence and prevalence of
      various types of cancers in Pakistan. AIM: To determine the frequency of
      malignant tumors seen in our practice and provide a foundation for building a
      comprehensive cancer care strategy. MATERIALS AND METHODS: 10,000 successive
      cases of solid malignant tumors reported in 2014 were included. All cases had
      formalin fixed, paraffin embedded specimens available and diagnosis was based on
      histological examination of H and E stained slides plus ancillary studies at the
      Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga
      Khan University Hospital, Karachi. The latest WHO classifications were used along
      with the latest CAP protocols for reporting and the most updated TNM staging.
      RESULTS: There were 9,492 (94.9%) primary tumors while 508 (5.1%) were
      metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in
      males. The commonest malignant tumors in females were breast (32%), esophagus
      (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they
      were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%)
      and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th
      decades. About 8% were seen under 20 years of age. CONCLUSIONS: Oral cavity and
      gastrointestinal cancers continue to be extremely common in both genders. Breast
      and esophageal cancers are prevalent in females. Lung and prostate cancer are
      less common than in the west. Ovarian cancer was very common but cervix cancer
      was less so.

PMID- 27039727
TI  - Roles of Ki67 in Breast Cancer - Important for Management?
AB  - BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen
      receptor (ER), progesterone receptor (PR) and human epidermal growth factor
      receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be
      associated with a poorer outcome, and despite absence of standardization of
      pathological assessment, is widely used for therapy decision making. We aim to
      study the role of the Ki-67 index in a group of Asian women with breast cancer.
      MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3
      invasive breast cancer in a single centre from July 2013 to Dec 2014 were
      included in this study. Univariable and multivariable logistic regression was
      used to determine the association between Ki-67 (positive defined as 14% and
      above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status
      and size. All analyses were performed using SPSS Version 22. RESULTS: In
      univariable analysis, Ki -67 index was associated with younger age, higher grade,
      ER and PR negativity, HER2 positivity, high mitotic index and positive lymph
      nodes. However on multivariable analysis only tumour size, grade, PR and HER2
      remained significant. Out of 102 stage 1 patients who had ER positive/PR
      positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki
      67 index and may have been offered chemotherapy. However, it is interesting to
      note that none of these patients received chemotherapy. CONCLUSIONS: Information
      on Ki67 would have potentially changed management in an insignificant proportion
      of patients with stage 1 breast cancer.

PMID- 27039728
TI  - Detection of Genital HPV Infection Using Urine Samples: a Population Based Study
      in India.
AB  - BACKGROUND: Cervical cancer is the second commonest cancer among Indian women and
      its association with human papilloma virus (HPV) is well established. This
      preventable cancer accounts for the maximum number of cancer related deaths among
      rural Indian women. Unlike in developed countries there are no organized cervical
      cancer screening programmes in India due to lack of resources and manpower.
      OBJECTIVE: To detect genital HPV infection using urine samples among asymptomatic
      rural women in the age group of 18-65 years. MATERIALS AND METHODS: The study
      area chosen was Perdoor village in Udupi Taluk, Karnataka State and all the women
      in the age group of 18-65 years formed the study cohort. A cross sectional study
      was conducted by house visits and 1,305 women were enrolled in the study. After
      taking written informed consent a data sheet was filled and early stream random
      urine samples were collected, transported to a laboratory at 4OC and aliquoted.
      Samples were tested using nested HPV PCR with PGMY09/11 and GP5+/6+ primers.
      Positive cases were genotyped by sequence analysis. RESULTS: Study participants
      included 1,134 sexually active and 171 unmarried women with a mean age at
      marriage of 22.1 (SD=3.9) years. Study area showed high female literacy rate of
      86.6%. Five urine samples tested positive for HPV DNA (0.4%). CONCLUSIONS: We
      found very low genital HPV infection rate among women from monogamous community.
      This is the first major population based study carried out among asymptomatic
      rural women to detect genital HPV infectio from Karnataka using urine samples.

PMID- 27039729
TI  - Novel Nonsense Variants c.58C>T (p.Q20X) and c.256G>T (p.E85X) in the CHEK2 Gene
      Identified dentified in Breast Cancer Patients from Balochistan.
AB  - Breast cancer is the most commonly occurring and leading cause of cancer deaths
      among women globally. Hereditary cases account 5-10% of all the cases and CHEK2
      is considered as a moderate penetrance breast cancer risk gene. CHEK2 plays a
      crucial role in response to DNA damage to promote cell cycle arrest and repair
      DNA damage or induce apoptosis. Our objective in the current study was to analyze
      mutations in the CHEK2 gene related to breast cancer in Balochistan. A total of
      271 individuals including breast cancer patients and normal subjects were
      enrolled. All 14 exons of CHEK2 were amplified and sequenced. The majority of the
      patients (>95%) had invasive ductal carcinomas (IDCs), 52.1% were diagnosed with
      tumor grade III and 56.1% and 27.5% were diagnosed with advance stages III and
      IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at
      exon 1 and 2 in two breast cancer patients were identified in the current study.
      Both the variants identified were novel and have not been reported elsewhere. 

PMID- 27039730
TI  - P16INK4a Immunostaining but Lack of Human Papilloma Virus Type 16 in Cutaneous
      Squamous Cell Carcinoma and Basal Cell Carcinoma: a Report from West Iran.
AB  - The tumor suppressor p16 is a biomarker for transforming human papilloma virus
      (HPV) infections that can lead to contradictory results in skin carcinomas. The
      aim of this study was to evaluate p16 expression and HPV-16 infection in the
      cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case
      control study was performed on paraffin blocks of BCCs and SCCs and normal skin
      (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for
      groups were stained with hematoxylin and eosin (H and E). Immunohistochemistry
      was performed for p16 expression and human papilloma virus type 16 (HPV-16)
      infection. Normal group was skin of mammoplasty specimens and normal skin tissue
      in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4
      years for normal, BCC and SCC groups, respectively. P16 positivity was more in
      SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all
      patients in three groups. Also, the mean age at diagnosis and P16-positivity were
      higher for the SCC group than the BCC group (P<0.005). In conclusion, in non
      melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor
      but there is no correlation between HPV-16 and p16 in these tumors. 

PMID- 27039731
TI  - Nurses and Television as Sources of Information Effecting Behavioral Improvement
      Regarding Liver Flukes in Nakhon Ratchasima Province, Thailand.
AB  - BACKGROUND: Liver fluke infection with Opisthorchis viverrini and its associated
      cholangiocarcinoma constitute a serious problem in Thailand. Healthy behavior can
      decrease infection, therefore, the investigation of knowledge, attitude, and
      practice is need required in high risk areas. OBJECTIVE: This study aimed to
      investigate the behavior and perceptions regarding liver fluke. MATERIALS AND
      METHODS: A cross-sectional descriptive study was conducted in Chum Phuang
      district of Nakhon Ratchasima province, Thailand during July to November 2015. A
      total 80 participants who had screened with verbal screening test, stool
      examination, and ultrasonography, were purposive selected and completed a pre
      designed questionnaire (Kruder-Richardon-20=0.80, Cronbach's alpha
      coefficient=0.82 and 0.79). T-test, ANOVA, and Pearson correlation test were used
      for analyzed data. RESULTS: The results reveal that O. viverrini infection was
      1.25%, and 3 patients had a dilated bile ducts. The participants had a high
      knowledge, attitude, and practice regarding liver fluke. The education,
      occupation, and income, were statistical significant to attitude regarding liver
      fluke. Nurses and television were the main sources of information regarding liver
      fluke, with statistical significance(p-value <0.05). Knowledge was significantly
      associated with attitude and practice (p-value<0.05). CONCLUSIONS: Participants
      had good behavior regarding liver fluke. Improvement of knowledge and attitude is
      influenced to practical change regarding this carcinogenic fluke. In addition,
      nurse and television are the main information resources for key success in
      increasing people perception for disease prevention and control in this area.

PMID- 27039732
TI  - Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with
      the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.
AB  - In the present study, we investigated the effects of motesanib (AMG 706), a
      multikinase inhibitor alone and in combination with DuP-697, an irreversible
      selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis
      induction in a human colorectal cancer cell line (HT29). Real time cell analysis
      (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer
      cell proliferation. Apoptosis was assessed with annexin V staining and
      angiogenesis was determined with chorioallantoic membrane model. We found that
      motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects
      on HT29 colorectal cancer cells. Combination with DUP-697 increased the
      antiproliferative, antiangiogenic and apoptotic effects. Results of this study
      indicate that motesanib may be a good choice in treatment of colorectal tumors.
      In addition, the increased effects of combination of motesanib with DuP-697 raise
      the possibility of using lower doses of these drugs and therefore avoid/minimize
      the dose-dependent side effects generally observed. 

PMID- 27039733
TI  - Effectiveness of a Health Educational Program Based on Self-Efficacy and Social
      Support for Preventing Liver Fluke Infection in Rural People of Surin Province,
      Thailand.
AB  - Opisthorchiasis is a major problem in Thailand particularly in northeast region
      which also has a high incidence of cholangiocarcinomas. Since health modification
      is needed, this quasi-experimental study aimed to assess the effectiveness of a
      health education program based on self-efficacy and social support in Tha Tum
      district, Surin province, Thailand. A total of 70 participants were purposive
      selected with a history of opisthorchiasis. Participants were divided into
      experimental and control groups, each with 35 subjects. The experimental group
      received a health education program composed of: (1) knowledge improvement,
      lectured with multimedia, demonstration, brochure, and handbook; (2) group
      discussion about their health beliefs, sharing their ideas and experience; and
      (3) social support from village health volunteers (VHV), heads of villages (HV),
      friends, and members of families, and public health officer (PHO). Follow-up was
      by PHO/VHV/HV, with provision of certificates and flasg for household that did
      not eat raw fish. Data were collected by predesigned questionnaires after
      implementation of the program for 3 months. Comparative data was analyzed by
      paired simple t-test and independent t-test. The results revealed that the
      experimental group had mean score of knowledge higher more than before the
      experiment (mean difference=3.1, t=3.915, 95%CI-3.3, -1.8 p-value=0.001), and the
      control group (mean difference=2.5, t=4.196, 95%CI=1.4, 3.6, p-value=0.001) with
      statistical significance. The mean scores of practice were higher than before the
      experiment (mean difference=4.6, t=4.331, 95%CI-5.3, -3.1, p-value=0.001), and
      control group (mean difference=4.4, t=6.142, 95%CI=4.2, 7.9, p-value=0.001) . The
      mean scores of perceived susceptibility and perceived severity of
      opisthorchiasis, al well as perceived benefits and perceived barriers to
      prevention of opisthorchiasis, were also higher than before the experiment and in
      the control group (p-value <0.001). In conclusion, this was a successful health
      education program for liver fluke avoidance. Therefore, it may useful for further
      behavior modification in the other epidemic areas. 

PMID- 27039734
TI  - Comparable Ablation Efficiency of 30 and 100 mCi of I-131 for Low to Intermediate
      Risk Thyroid Cancers Using Triple Negative Criteria.
AB  - BACKGROUND: There is controversy about ablation efficacy of low or high doses of
      radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The
      purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi
      of RAI to achieve successful ablation in patients with low to intermediate risk
      DTC. MATERIALS AND METHODS: This prospective cross sectional study was conducted
      from April 2013 to November 2015. Inclusion criteria were patients of either
      gender, 18 years or older, having low to intermediate risk papillary and
      follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant
      metastasis.Thirty-nine patients were administered 30 mCi of RAI while 61 patients
      were given 100 mCi. Informed consent was acquired from all patients and
      counseling was done by nuclear physicians regarding benefits and possible side
      effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after
      thyroxin withdrawal), these patients were followed up for stimulated TSH,
      thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a
      diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful
      ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies,
      negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve
      analysis was used to find diagnostic strength of baseline sTg to predict
      successful ablation. RESULTS: Successful ablation based upon triple negative
      criteria was 56% in the low dose and 57% in the high dose group (non-significant
      difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82%
      and 77% (again non-significant). The ROC curve revealed that a baseline sTg level
      <= 7.4 ng/ml had the highest diagnostic strength to predict successful ablation
      in all patients. CONCLUSIONS: We conclude that 30 mCi of RAI has similar ablation
      success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline
      sTg <= 7.4 ng/ml is a strong predictor of successful ablation in all patients.
      Low dose RAI is safer, more cost effective and more convenient for patients and
      healthcare providers.

PMID- 27039735
TI  - Anti Tumoral Properties of Punica granatum (Pomegranate) Seed Extract in
      Different Human Cancer Cells.
AB  - BACKGROUND: Punica granatum (PG) has been demonstrated to possess antitumor
      effects on various types of cancer cells. In this study, we determined
      antiproliferative properties of a seed extract of PG (PSE) from Iran in different
      human cancer cells. MATERIALS AND METHODS: A methanolic extract of pomegranate
      seeds was prepared. Total phenolic content (TPC) and total flavonoid content
      (TFC) were assessed by colorimetric assays. Antioxidant activity was determined
      with reference to DPPH radical scavenging activity. The cytotoxicity of different
      doses of PSE (0, 5, 20, 100, 250, 500, 1000 MUg/ml) was evaluated by MTT assays
      with A549 (lung non small cell carcinoma), MCF-7 (breast adenocarcinoma), SKOV3
      (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. RESULTS:
      Significant (P<0.01) or very significant (P<0.0001) differences were observed in
      comparison to negative controls at all tested doses (5-1000 MUg/ml). In all
      studied cancer cells, PSE reduced the cell viability to values below 23%, even at
      the lowest doses. In all cases, IC50 was determined at doses below 5 MUg/ml. In
      this regard, SKOV3 ovarian cancer cells were the most responsive to
      antiproliferative effects of PSE with a maximum mean growth inhibition of 86.8%
      vs. 82.8%, 81.4% and 80.0% in MCF-7, PC-3 and A549 cells, respectively.
      CONCLUSIONS: Low doses of PSE exert potent antiproliferative effects on different
      human cancer cells SKOV3 ovarian cancer cells as most and A549 cells ar least
      responsive regarding cytotoxic effects. However, the mechanisms of action need to
      be addressed.

PMID- 27039736
TI  - Survival Outcomes of Advanced and Recurrent Cervical Cancer Patients Treated with
      Chemotherapy: Experience of Northern Tertiary Care Hospital in Thailand.
AB  - Chemotherapy is the primary treatment for advanced and recurrent cervical cancer.
      To evaluate the survival outcomes of chemotherapy and the prognostic factors in
      this setting, we conducted a retrospective study by reviewing the medical records
      of advanced and recurrent cervical cancer patients treated with systemic
      chemotherapy at our institute between January, 2008 and December, 2014. One
      hundred and seventy-three patients met the criteria with a mean age of 50.9
      years. 4.1% of them were HIV positive. The most common initial stage was stage
      IVB (30.1%) and the most common histology was squamous cell carcinoma (68.6%).
      Ninety-two (53.2%) patients were previously treated with concurrent
      chemoradiation with 53% developing combined sites of recurrence. The median
      recurrence free interval was 16.7 months. Cisplatin + 5 fluorouracil (5FU)
      (53.2%) was the most frequent first line chemotherapy followed by carboplatin +
      paclitaxel (20.2%) with an objective response of 39.3%. Seventy-two patients
      received subsequent chemotherapy. The median overall survival of all studied
      patients was 13.2 months. Only a recurrence free interval of less than 12 months
      was an independent prognostic factor for survival outcome. In conclusion,
      chemotherapy treatment for advanced and recurrent cervical cancer patients showed
      modest efficacy with a shorter recurrence free survival less than 12 months as a
      significant poor prognosis factor. 

PMID- 27039737
TI  - Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal
      Abnormal Cytology Lesions and Cancer Tissues from Thai Women.
AB  - Vulva and Vaginal cancers are rare among all gynecological cancers worldwide,
      including Thailand, and typically affect women in later life. Persistent high
      risk human papillomavirus (HR-HPV) infection is one of several important causes
      of cancer development. In this study, we focused on HPV investigation and
      specific type distribution from Thai women with abnormality lesions and cancers
      of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva
      and Vaginal abnormalities and cancer cells with histologically confirmed were
      collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer
      Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain
      reaction and enzyme immunoassay with GP5+/ bio 6+ consensus specific primers and
      digoxigenin-labeled specific oligoprobes, respectively. The human beta-globin
      gene was used as an internal control. Overall results represented that HPV
      frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and
      abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%)
      samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV
      DNA positive. Single HPV type and multiple HPV type infection could be observed
      in both type of cancers and abnormal lesion samples in the different histological
      categorizes. HPV16 was the most frequent type in all cancers and abnormal
      cytology lesions, whereas HPV 18 was less frequent and could be detected as co
      infection with other high risk HPV types. In addition, low risk types such as HPV
      6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion
      samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types;
      HPV 16 and 31. In conclusion, from our results in this study we suggest that
      women with persistent high risk HPV type infection are at risk of developing
      vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of
      these, similar to the cervical cancer cases. Although the number of samples in
      this study was limited and might not represent the overall incidence and
      prevalence in Thai women, but the baseline data are of interest and suggest
      further study for primary cancer screening and/or developing the efficiency of
      prophylactic HPV vaccines in Thailand. 

PMID- 27039738
TI  - Evaluation of Head and Neck Cancer Awareness and Screening Status in Jeddah,
      Saudi Arabia.
AB  - BACKGROUND: Head and neck cancer (HNC) is one of the deadliest cancers worldwide.
      Early detection is a key determinant of HNC prognosis. Hence, raising awareness
      of this disease may improve survival rates. The present study evaluated the level
      of awareness and screening status for HNC in the general population of Jeddah,
      Saudi Arabia. MATERIALS AND METHODS: An e-questionnaire was distributed during
      our HNC awareness campaign at the Red Sea Mall in Jeddah. The questions assessed
      HNC knowledge and screening status among participants. RESULTS: Of the 112
      respondents, 68% indicated that they had no knowledge of HNC. Social media was
      the major source of information (39%) for respondents. The majority (40%)
      believed that it was the joint responsibility of dentists, dental hygienists, and
      general physicians to screen for HNC; 82% had never been screened. CONCLUSIONS:
      Knowledge and awareness of HNC must be increased in the general population and
      among dental health professionals.

PMID- 27039739
TI  - Association of the Glutathione S-transferase T1 Null Genotype with Risk of
      Gastric Cancer: a Meta-analysis in Asian Populations.
AB  - BACKGROUND: A large number of studies have been published to investigate the
      association between the null genotype of glutathione S-transferase T1 (GSTT1)
      with gastric cancer. However, the results were inconsistent and conflicting. The
      aim of this study was to estimate the relationship between this polymorphism in
      the GSTT1 gene and gastric cancer risk in Asian populations by meta-analysis.
      MATERIALS AND METHODS: A literature search was performed in PubMed, Embase,
      Chinese Biomedical database (CBM), Weipu database, Wanfang database, and China
      National Knowledge Infrastructure database (CNKI). Statistical analysis was
      conducted by using Review Manager 5.3. RESULTS: Thirty-nine studies with a total
      of 7,737 gastric cancer cases and 10,823 controls were included in this meta
      analysis. The meta-analysis of total studies showed that the null genotype in
      GSTT1 was associated with increased risk of gastric cancer in Asians (OR=1.19,
      95% CI=1.08-1.31, p=0.0002). Subgroup analysis showed a significant relationship
      between GSTT1 null genotype and gastric cancer in East-Asians, as well as in
      subgroup analysis of hospital-based design. On subgroup analysis by smoking
      status, alcohol status, Helicobacter pylori infection status, and histology type,
      no significant association of this polymorphism with susceptibility to gastric
      cancer was found. CONCLUSIONS: In conclusion, the results showed that the null
      genotype of GSTT1 is significantly associated with an increased risk in gastric
      cancer in Asian populations.

PMID- 27039740
TI  - Sentinel Node Biopsy Examination for Breast Cancer in a Routine Laboratory
      Practice: Results of a Pilot Study.
AB  - BACKGROUND: Examination of sentinel lymph node (SLN) biopsies provides accurate
      nodal staging for breast cancer and plays a key role in patient management.
      Procurement of SLNs and the methods used to process specimens are equally
      important. Increasing the level of detail in histopathological examination of
      SLNs increases detection of metastatic tumours but will also increase the burden
      of busy laboratories and thus may not be carried out routinely. Recommendation of
      a reasonable standard in SLN examination is required to ensure high sensitivity
      of results while maintaining a manageable practice workload. MATERIALS AND
      METHODS: Twenty-four patients with clinically node-negative breast cancer were
      recruited. Combined radiotracer and blue dye methods were used for identification
      of SLNs. The nodes were thinly sliced and embedded. Serial sectioning and
      immunohistochemical (IHC) staining against AE1/AE3 were performed if initial
      HandE sections of the blocks were negative. RESULTS: SLNs were successfully
      identified in all patients. Ten cases had nodal metastases with 7 detected in
      SLNs and 3 detected only in axillary nodes (false negative rate, FNR=30%). Some 5
      out of 7 metastatic lesions in the SLNs (71.4%) were detected in initial sections
      of the thinly sliced tissue. Serial sectioning detected the remaining two cases
      with either micrometastases or isolated tumour cells (ITC). CONCLUSIONS: Thin
      slicing of tissue to 3-5mm thickness and serial sectioning improved the detection
      of micro and macro-metastases but the additional burden of serial sectioning gave
      low yield of micrometastases or ITC and may not be cost effective. IHC validation
      did not further increase sensitivity of detection. Therefore its use should only
      be limited to confirmation of suspicious lesions. False negative cases where SLNs
      were not involved could be due to skipped metastases to non-sentinel nodes or
      poor technique during procurement, resulting in missed detection of actual SLNs.

PMID- 27039741
TI  - Investigation of the Role of Training Health Volunteers in Promoting Pap Smear
      Test Use among Iranian Women Based on the Protection Motivation Theory.
AB  - BACKGROUND: Cervical cancer is known as one of the most prevalent types of
      cancers and a major public health problem in developing countries which can be
      detected by Pap test, prevented, and treated. Despite the effective role of Pap
      test in decreasing the incidence and mortality due to cervical cancer, it is
      still one the most common causes of cancer-related deaths among women, especially
      in developing countries. Thus, this study aimed to examine the effect of
      educational interventions implemented by health volunteers based on protection
      motivation theory (PMT) on promoting Pap test use among women. MATERIALS AND
      METHODS: This quasi-experimental study was conducted on 60 health volunteers and
      420 women. The study participants were divided into an intervention and a control
      group. Data were collected using a valid self-reported questionnaire including
      demographic variables and PMT constructs which was completed by both groups
      before and 2 months after the intervention. Then, the data were entered into the
      SPSS statistical software, version 19 and were analyzed using Chi-square test,
      independent T-test, and descriptive statistical methods. P<0.05 was considered as
      statistically significant. RESULTS: The findings of this study showed that the
      mean scores of PMT constructs (i.e. perceived vulnerability, perceived severity,
      fear, response-costs, self-efficacy, and intention) increased in the intervention
      group after the intervention (P<0.001). However, no significant difference was
      found between the two groups regarding response efficacy after the intervention
      (P=0.06). The rate of Pap test use also increased by about 62.9% among the study
      women. CONCLUSIONS: This study showed a significant positive relationship between
      PMT-based training and Pap test use. The results also revealed the successful
      contribution of health volunteers to training cervical cancer screening. Thus,
      training interventions based on PMT are suggested to be designed and implemented
      and health volunteers are recommended to be employed for educational purposes and
      promoting the community's, especially women's, health.

PMID- 27039742
TI  - Plasma Peptidome as a Source of Biomarkers for Diagnosis of Cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is the bile duct cancer which constitutes one of the
      important public health problems in Thailand with high mortality rate, especially
      in the Opisthorchis viverrini (a parasite risk factor for CCA) endemic area of
      the northeastern region of the country. This study aimed to identify potential
      biomarkers from the plasma peptidome by CCA patients. Peptides were isolated
      using 10 kDa cut-off filter column and the flow-through was then used as a
      peptidome for LC-MS/MS analysis. A total of 209 peptides were obtained. Among
      these, 15 peptides were concerned with signaling pathways and 12 related to
      metabolic, regulatory, and biosynthesis of secondary metabolite pathways. Five
      exclusive peptides were identified as potential biomarkers, i.e. ETS domain
      containing transcription factor ERF (P50548), KIAA0220 (Q92617),
      phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
      isoform 1 (P42338), LP2209 (Q6XYC0), and casein kinase II subunit alpha (P19784).
      Three of these biomarkers are signaling related molecules. A combination of these
      biomarkers for CCA diagnosis is proposed. 

PMID- 27039743
TI  - Prognostic Factors and Clinical Outcome in Parotid Gland Tumors: a Single
      Institution Experience from the Eastern Black Sea Region of Turkey.
AB  - PURPOSE: To review clinical characteristics, treatment outcomes and prognostic
      factors in patients with parotid gland tumors treated with surgery and
      postoperative radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed 69
      patients with parotid gland tumors, with a median follow-up of 52 months (range,
      2-228 months). and a median radiotherapy dose of 60Gy (range, 30-69 Gy). RESULTS:
      There were 24 (35%) females and 45 (65%) males, at a ratio of 1/1.9. Median age
      at presentation was 58.9+/-17.2 (range 13-88) years. The most common histology
      was adenoid cystic carcinoma (33%) and mucoepidermoid carcinoma (28%). The mean
      overall survival (OS) was 65.3+/-8 (95% confidence interval [CI], 49.6-81.1)
      months and the median overall survival was 40.0 +/- 7 (95% CI, 26.2-53.7) months.
      The -1, -3, -5 and -10 year OS rates were 78%, 52.4%, 35.3% and 19.6%
      respectively. The mean disease free survival (DFS) was 79.2+/-10 (95% CI, 59.3
      97.1) months and the median disease free survival was 38+/-13 (95% CI, 7.05-88.7)
      months. The -1,-3,-5 and -10 year DFS rates were 71.9%, 50.1%, 43.7% and 30.1%
      respectively. On univariate analysis, the OS was significantly better with female
      sex (p<0.005), < 50 age (p<0.021), T stage (p<0.0001), absence of lymph node
      involvement (p<0.0001), lower tumor grade (p<0.0001), absence of lymphovascular
      invasion (p<0.002), absence of perineural invasion (p<0.0001), absence of
      extracapsuler extension (p<0.0001), surgical margin negativity (p<0.006), <=60 Gy
      radiotherapy dose (p<0.0001) and absence of distant metastasis (p<0.027).
      CONCLUSIONS: Employing existing standards of postoperative radiotherapy is a
      possible treatment that was found to be mainly effective in patients with parotid
      gland carcinomas.

PMID- 27039744
TI  - Distribution of KRAS and BRAF Mutations in Metastatic Colorectal Cancers in
      Turkish Patients.
AB  - The results of this study demonstrate the potential prognostic and predictive
      values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC).
      It has been proven that KRAS and BRAF mutations are predictive biomarkers for
      resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic
      CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and
      BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared
      the results with clinicopathological data. KRAS and BRAF mutations were
      identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS
      mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of
      the positive patients, respectively. The KRAS mutation frequency was
      significantly higher in tumors located in the ascending colon (p=0.043). Thus, we
      found that approximately 1/3 of the patients with mCRC had KRAS mutations and the
      only clinicopathological factor related to this mutation was tumor location.
      Future studies with larger patient groups should yield more accurate data
      regarding the molecular mechanism of CRC and the association between KRAS and
      BRAF mutations and clinicopathological features. 

PMID- 27039745
TI  - Effect of Neoadjuvant Chemotherapy on Axillary Lymph Node Positivity and Numbers
      in Breast Cancer Cases.
AB  - BACKGROUND: The aim of this study is to compare the numbers of axillary lymph
      nodes (ALN) taken out by dissection between patients with breast cancer operated
      on after having neoadjuvant chemotherapy (NAC) treatment and otherswithout having
      neoadjuvant chemotherapy, and to investigate factors affecting lymph node
      positivity. MATERIALS AND METHODS: A total of 49 patients operated due to
      advanced breast cancer after neoadjuvant chemotherapy and 144 patients with a
      similar stage of the cancer having primary surgical treatment without
      chemotherapy at the general surgery clinic of Ondokuz Mayis University Medicine
      Faculty between the dates 01.01.2006 and 31.10.2012 were included in the study.
      The total number of lymph nodes taken out by axillary dissection (ALND) was
      categorized as the number of positive lymph nodes and divided into <10 and >=10.
      The variables to be compared were analysed using the program SPSS 15.0 with
      P<0.05 accepted as significant. RESULTS: Median number of dissected lymph nodes
      from the patient group having neoadjuvant chemotherapy was 16 (16-33) while it
      was 20 (5-55) without chemotherapy. The respective median numbers of positive
      lymph nodes were 5 ( 0-19) and 10 (0-51). In 8 out of 49 neoadjuvant chemotherapy
      patients (16.3%), the number of dissected lymph nodes was below 10, and it was
      below 10 in 17 out of 144 primary surgery patients. Differences in numbers of
      dissected total and positive lymph nodes between two groups were significant, but
      this was not the case for numbers of <10 lymph nodes. CONCLUSIONS: The number of
      dissected lymph nodes from the patients with breast cancer having neoadjuvant
      chemotherapy may be less than without chemotherapy. This may not always be
      attributed to an inadequate axillary dissection. More research to evaluate the
      numbers of positive lymph nodes are required in order to increase the reliability
      of staging in the patients with breast cancer undergoing neoadjuvant
      chemotherapy.

PMID- 27039746
TI  - Predictors of Positive Bone Metastasis in Newly Diagnosed Prostate Cancer
      Patients.
AB  - BACKGROUND: The prevalence of prostate cancer (PCa) has been increasing in recent
      years. Treatment strategies are largely based on the results of bone scan
      screening. Therefore, our aim was to investigate predictors of positive bone
      metastasis in newly diagnosed PCa patients. MATERIALS AND METHODS: After
      extensive review, 336 consecutive patients newly diagnosed with PCa between April
      2010 and November 2013 at our institution were enlisted in the study. Patients
      were divided into two groups according to bone scan results. Univariate analyses
      (Chi-square test for discrete variables and independent t-test for continuous
      variables) were applied to determine the potentially significant risk factors
      associated with distant bone metastasis. Binary logistic regression analyses were
      used to further investigate the influence of these factors on bone metastasis.
      RESULTS: The patient mean age was 71.9 +/- 8.6 years (range: 48 to 94 years). The
      mean prostate specific antigen (PSA) level and biopsy Gleason score were 260.2 +/
      1107.8 ng/mL and 7.4 +/- 1.5, respectively. The body mass index (BMI) for the
      series was 24.5 +/- 3.4 kg/m2. Sixty-four patients (19.0%) had a positive bone
      scan result. Patients with positive bone scan results had a significantly lower
      BMI (23.3 +/- 3.5 vs. 24.8 +/- 3.3; p=0.003), a higher Gleason score (8.5 +/- 1.1
      vs. 7.1 +/- 1.5; p < 0.001), and a higher PSA level (1071.3 +/- 2337.1 vs. 69.4
      +/- 235.5; p < 0.001) than those without bone metastasis. Multivariate logistic
      regression analysis employing the above independent predictors demonstrated that
      a Gleason score of >=7, clinical stage >=T3, BMI <=22 kg/m2, and an initial PSA
      level of >=20 ng/mL were all independent predictors of bone metastasis.
      CONCLUSIONS: A bone scan might be necessary in newly diagnosed PCa patients with
      any of the following criteria: clinical stage T3 or higher, a Gleason score of 7
      or higher, BMI equal to or less than 22, and a PSA level of 20 or higher.

PMID- 27039747
TI  - Survival of Colorectal Cancer in the Presence of Competing- Risks - Modeling by
      Weibull Distribution.
AB  - BACKGROUND: Colorectal cancer (CRC) is the commonest malignancy in the lower
      gastrointestinal tract in both men and women. It is the third leading cause of
      cancer-dependent death in the world. In Iran the incidence of colorectal cancer
      has increased during the last 25 years. MATERIALS AND METHODS: In this article we
      analyzed the survival of 447 colorectal patients of Taleghani hospital in Tehran
      using parametric competing-risks models. The cancers of these patients were
      diagnosed during 1985 - 2012 and followed up to 2013. The purpose was to assess
      the association between survival of patients with colorectal cancer in the
      presence of competing-risks and prognostic factors using parametric models. The
      analysis was carried out using R software version 3.0.2. RESULTS: The prognostic
      variables included in the model were age at diagnosis, tumour site, body mass
      index and sex. The effect of age at diagnosis and body mass index on survival
      time was statistically significant. The median survival for Iranian patients with
      colorectal cancer is about 20 years. CONCLUSIONS: Survival function based on
      Weibull model compared with Kaplan-Meier survival function is smooth. Iranian
      data suggest a younger age distribution compared to Western reports for CRC.

PMID- 27039748
TI  - Effects of Millimetric Shifts in Breast Cancer Radiotherapy on the Radiation Dose
      Distribution.
AB  - BACKGROUND: This study aimed to facilitate decision-making in cases of breast
      cancer radiotherapy shifts by simulating millimetric shifts and analyzing their
      effects on dose distribution. METHODS: The study included 30 patients with left
      side breast cancer who were treated with three dimensional conformal radiotherapy
      (3D-CRT) in the Radiation Oncology Department in Hatay Public Hospital, between
      January 2013 and April 2015. A treatment plan shifting at three axes with six
      different measures was simulated. RESULTS: The biggest difference in values was
      (+3mm shift) 476cGy, with a 7.7 % change for heart and 25.6% for spinal cord. The
      shifts in values respectively for CTV min, mean, max were -4.8%, 2.5%, 4%. The
      differences for lymphatic min, mean, max were 21.3%, 20.3%, -12.2%. CONCLUSION:
      The most important thing is not the treatment plan quality, but its practicality.
      The treatment plan must be practical and its practice must be controlled rigidly.

PMID- 27039749
TI  - Educational Activities for Rural and Urban Students to Prevent Skin Cancer in Rio
      Grande do Sul, Brazil.
AB  - BACKGROUND: Excessive exposure to the sun during childhood is strongly associated
      with the development of skin cancer in the future. The only way to prevent the
      development of skin cancer is to protect against ultraviolet radiation, which can
      be achieved through strategic awareness during childhood and adolescence.
      OBJECTIVE: The aim of this work was to evaluate the impact of educational
      activities for rural and urban students to promote the use of sunscreens and
      prevent skin cancer. MATERIALS AND METHODS: This study was carried out with
      students (9-12 years) of rural (n=70) and urban (n=70) schools in Rio Grande do
      Sul state, Brazil. The educational interventions were lectures and games. The
      impact of this strategy was evaluated through the application of a questionnaire
      before and after the interventions. RESULTS: Before the intervention, it was
      found around 50% of rural and urban students were not aware of the damage caused
      by sun exposure, often exposing themselves to UV radiation without use sunscreen
      ( ~ 25 %) and at the most critical times of the day/year. After the lectures we
      observed an improvement in the behavior of the students with regard to sun
      exposure and knowledge about skin cancer. CONCLUSIONS: The results of this study
      emphasize the importance of prevention strategies for skin cancer and promoting
      the use of sunscreens based educational strategies. The interventions were of
      great value in relation to disseminating knowledge on the subject.

PMID- 27039750
TI  - Age of initiation, Determinants and Prevalence of Cigarette Smoking among
      Teenagers in Mushin Local Government Area of Lagos State, Nigeria.
AB  - BACKGROUND: Cigarette smoking constitutes a major threat to the health and
      wellbeing of teenagers. While smoking has been on decline in the developed
      countries, the reverse is the case in developing countries. The aim of this study
      was to determine the age of initiation, determinants and prevalence of cigarette
      smoking among teenagers in Mushin Local Government Area of Lagos state, Nigeria.
      MATERIALS AND METHODS: This was a descriptive cross-sectional study among 475
      teenagers selected by multistage sampling. A pre-tested, structured, interviewer
      administered questionnaire was used for data collection. The study was carried
      out in November, 2014. RESULTS: Response rate was 84.6%. Mean age of the
      respondents was 16.4+/-1.65years. Range and mean age of initiation of cigarette
      smoking were 7 to 17 years and 12.0+/-3.32 years respectively. Teenagers who were
      above 15 years (OR:5.13, 95%CI: 0.87-30.26), males (OR:5.19, 95%CI: 1.57-17.18),
      married (OR:8.41, 95%CI: 1.04- 63.35), had <=primary school education(OR:4.31,
      95%CI: 1.07-17.33), influenced by friends(OR:308.84, 95%CI: 84.87-1123.81), and
      influenced by advertisements (OR:27.83, 95%CI: 3.92-197.64) were more likely to
      have initiated cigarette smoking. Furthermore, teenagers who were males
      (OR:12.77, 95%CI: 2.90-56.28), married (OR:19.24, 95%CI: 2.05-180.45), had
      <=primary school education(OR:7.85, 95%CI: 2.37-26.01), influenced by
      friends(OR:28.56, 95%CI: 10.86-75.07), and influenced by advertisements (OR:5.95,
      95%CI: 1.72-20.61) were more likely to be current cigarette smokers. In addition,
      24.9% had initiated cigarette smoking while 14.7% were current smokers of
      cigarette. CONCLUSIONS: Mean age of initiation of cigarette smoking was 12.0+/
      3.32 years. Determinants of cigarette smoking were age, gender, marital status,
      educational background, friends and advertisements. Life time prevalence of
      cigarette smoking was higher than prevalence of current cigarette smokers.
      Cigarette smoking reduction programs should take these factors into
      consideration.

PMID- 27039751
TI  - The C609T (Pro187Ser) Null Polymorphism of the NQO1 Gene Contributes
      Significantly to Breast Cancer Susceptibility in North Indian Populations: a Case
      Control Study.
AB  - BACKGROUND: Worldwide, breast cancer is the most common cancer among women and is
      a leading cause of cancer death. In the present study, we investigated the NQO1
      C609T genotypic and allelic distribution in north Indian breast cancer patients.
      MATERIALS AND METHODS: The genotypic distribution of the NQ01 C609T polymorphism
      was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and
      100 healthy controls using allele specific PCR (AS-PCR). RESULTS: A lower
      frequency of the CC genotype was found in breast cancer patients (24%) than in
      the controls. On the other hand, TT genotype frequency was also found to be
      higher in female healthy controls (32%) than the female breast cancer patients
      (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%,
      56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not
      find any significant correlation between the NQO1 C609T polymorphism and age
      group, grading, menopausal status and distant metastasis. A less significant
      association was found between the NQ01 C609T polymorphism and the stage of breast
      cancer (X2=5.931, P=0.05). CONCLUSIONS: The present study shows a strong
      association between NQO1 C609T polymorphism with the breast cancer risk in the
      north Indian breast cancer patients so that possible use as a risk factor should
      be further explored.

PMID- 27039752
TI  - Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta
      Analysis Findings.
AB  - PURPOSE: To investigate any potential association between wine and breast cancer
      risk. MATERIALS AND METHODS: We quantitatively assessed associations by
      conducting a meta-analysis based on evidence from observational studies. In May
      2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library
      to identify studies examining the effect of wine drinking on breast cancer
      incidence. The relative risk (RR) or odds ratio (OR) were used to measure any
      such association. RESULTS: The analysis was further stratified by confounding
      factors that could influence the results. A total of twenty-six studies (eight
      case-control and eighteen cohort studies) involving 21,149 cases were included in
      our meta-analysis. Our study demonstrated that wine drinking was associated with
      breast cancer risk. A 36% increase in breast cancer risk was observed across
      overall studies based on the highest versus lowest model, with a combined RR of
      1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from
      wine seemed to have protective value from our non-linear model. CONCLUSIONS: Our
      findings indicate that wine drinking is associated with breast cancer risk in a
      dose-dependent manner. High consumption of wine contributes to breast cancer risk
      with protection exerted by low doses. Further investigations are needed for
      clarification.

PMID- 27039753
TI  - Effects of a School-based Intervention Program on Attitude and Knowledge of
      Household Members Towards a Smoke-free Home: a Cluster Controlled Trial.
AB  - BACKGROUND: A school-based smoke free home (SFH) program is useful in empowering
      the mother and child to reduce secondhand smoke exposure but the effects of
      pretesting on knowledge and attitude has been largely ignored. We aimed to test
      whether such a program can be effective in Southern Thailand with an additional
      assessment of the net effect of the pretest. MATERIALS AND METHODS: A Solomon
      four-group design was used. Twelve rural primary schools were assigned to one of
      the four conditions (each with 3 schools): intervention with and without a
      pretest, control with and without the same pretest. The intervention was
      performed in the classroom and home over a period of 1 month. Outcomes were
      assessed at baseline and 3 months after the intervention on whether the home was
      smoke free and related knowledge and attitude. RESULTS: The intervention could
      lead to a smoke-free home without statistical significance. Attitude, knowledge
      and self-confidence on creating a smoke-free home, and self-confidence in
      avoidance of secondhand smoke exposure and persuading smokers to not smoke in
      their home were significantly improved. No pretest effect was observed.
      CONCLUSIONS: Gain in attitude, knowledge and self-confidence among family members
      from the brief school-based education should be enhanced by other measures.

PMID- 27039754
TI  - p53, Cyclin D1, p21 (WAF1) and Ki-67 (MIB1) Expression at Invasive Tumour Fronts
      of Oral Squamous Cell Carcinomas and Development of Local Recurrence.
AB  - BACKGROUND: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was
      evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these
      markers at invasive tumour fronts (ITFs) could predict the development of local
      recurrence. MATERIALS AND METHODS: Archived paraffin-embedded specimens from 51
      patients with T1/T2 tumours were stained immunohistochemically and analysed
      quantitatively. Local recurrence-free survival was tested with Kaplan-Meier
      survival plots (log-rank test) using median values to define low and high
      expression groups and with a Cox's proportional hazards model in which the
      expression scores were entered as continuous variables. RESULTS: The assessment
      of expression of all markers was highly reliable, univariate analysis showing
      that patients with clear surgical margins, with low cyclin D1 and high p21
      expression at the ITF had the best local recurrence-free survival. Multivariate
      analysis showed that these three parameters were independent prognostic factors
      but that neither p53 nor MIB1 expression were of prognostic value. CONCLUSIONS:
      Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help
      to predict local recurrence in early stage oral squamous cell carcinoma cases.

PMID- 27039755
TI  - Clinicopathological Correlation Study of Oral Squamous Cell Carcinoma in a Local
      Indian Population.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC), the most common malignancy of
      the oral cavity, shows geographical variation with respect to the age, sex, site
      and habits of the population. The histolopathologic grade of the tumor is closely
      related to its tissue of origin. This study was conducted to establish the
      prevalence of OSCC in relation to patient sex, age, habits and sites of lesions.
      MATERIALS AND METHODS: A total of 130 cases of histopathologically diagnosed OSCC
      were selected for the study, out of which 66, 38 and 26 were well (WD),
      moderately (MD)and poorly differentiated (PD), respectively. Sections were
      stained with haematoxylin and eosin and graded according to a modified Borders's
      system. Then statistically analyzed different grades of OSCC for correlations
      with other variables. RESULTS: In our study the majority cases of OSCC were found
      in the 5th to 7th decades of life, males acconting for 53%. The most common site
      was the buccal mucosa and most cases had habit of tobacco use either in the form
      of chewing or smoking or both. When the different grades of OSCC were compared
      with different sites a statistically significant value was observed (P=0.029).
      CONCLUSIONS: The incidence of high grade PD is very much less in female patients
      but in males such lesions were common. In our location population the buccal
      mucosa is the most common site due to the tobbaco habits of the patients and
      majority cases of the buccal mucosa are WD whereas in tongue, floor of the mouth
      and palate PD are common.

PMID- 27039756
TI  - Clinical Efficacy of a Mouth-Exercising Device Adjunct to Local Ointment Intra
      Lesional Injections and Surgical Treatment for Oral Submucous Fibrosis: a
      Randomized Controlled Trial.
AB  - BACKGROUND: Oral physiotherapy or mouth exercise is considered to be an adjunct
      but mandatory treatment modality for oral submucous fibrosis (OSMF). This study
      planned to evaluate the clinical efficacy of a newly designed mouth exercising
      device (MED) in OSMF patients receiving local ointment, intra-lesional drugs and
      surgical treatment. MATERIALS AND METHODS: A total of 231 OSMF patients were
      selected and treated with basic regime including topical corticosteroids, oral
      antioxidants and the icecream-stick exercise regime and allotted randomly to two
      equal groups A and B. Group-A patients were additionally given MED. Subgroups A1
      and B1 patients with an inter-incisal distance (IID) 20-35mm were not given any
      additional therapy; subgroup A2 and B2 patients (IID 20-35mm) were treated
      additionally with intra-lesional injections. Subgroups A3 and B3 with IID<20mm
      were managed surgically. IID was measured at baseline and at 6 months recall. The
      change in IID measurements was calculated and statistically analyzed using 2-way
      ANOVA and Tukeys multiple post hoc analysis. RESULTS: Average improvement in IID
      after six months of recall visits was observed to be 8.4 mm in subgroup-A1 (n-53)
      compared to 5.5 mm in B1(n-50) (p<0.01). The IID improvement in subgroup-A2 was
      found to be 9.3mm (n-46) compared to 5.1 mm in B2 (n-48) (p<0.01). In the surgery
      group, mouth opening improvement was observed to be 9.6 mm in subgroup A3 (n-18)
      compared to 4.8 mm for B3 (n-16) (p<0.01). CONCLUSIONS: Use of the MED appears to
      be effective for increasing oral opening in OMSF patients in conjunction with
      local, injection and/or surgical treatment.

PMID- 27039757
TI  - Expression of p53 Breast Cancer in Kurdish Women in the West of Iran: a Reverse
      Correlation with Lymph Node Metastasis.
AB  - BACKGROUND: In breast cancer (BC), it has been suggested that nuclear
      overexpression of p53 protein might be an indicator of poor prognosis. The aim of
      the current study was to evaluate the expression of p53 BC in Kurdish women from
      the West of Iran and its correlation with other clinicopathology figures.
      MATERIALS AND METHODS: In the present retrospective study, 231 patients were
      investigated for estrogen receptor (ER) and progesterone receptor (PR)
      positivity, defined as >=10% positive tumor cells with nuclear staining. A binary
      logistic regression model was selected using Akaike Information Criteria (AIC) in
      stepwise selection for determination of important factors. RESULTS: ER, PR, the
      human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%,
      55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two
      groups: 54.5% had Ki67<20% and 45.5% had Ki67 >=20%. Of 214 patients, 137(64%)
      had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion.
      Binary logistic regression analysis showed that there was inverse significant
      correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025
      0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation
      between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53.
      CONCLUSIONS: As in a number of studies, expression of p53 had a inverse
      correlation with lymph node metastasis and ER status and also a direct
      correlation with HER2 status. Also, p53-positivity is more likely in triple
      negative BC compared to other subtypes.

PMID- 27039758
TI  - Lack of Relationship of Egg White Intake with Occurrence of Leukopenia in
      Gynecologic Cancer Patients during Chemotherapy.
AB  - Egg white intake during chemotherapy is common advice for cancer patients for the
      prevention of leukopenia. However, the benefit is uncertain. We conducted this
      prospective study to identify the relationship of egg white intake for
      gynecologic cancer patients who received carboplatin and paclitaxel and the
      occurrence of leukopenia. Between January 2014 and January, 2015, 81 patients
      were interviewed regarding their intake of egg whites before receiving subsequent
      chemotherapy. The basic data, the details of egg white intake and the grade of
      leukopenia in the previous cycle were recorded. The mean age was 54.1 years and
      80% of the patients had a diagnosis of ovarian or endometrial cancer. The
      patients were interviewed at cycles 1-3 in 45 cases, 4-6 in 45 cases and 7-9 in
      two cases. Subsequent dose reduction was found in 6.2% and granulocyte
      stimulating growth factors was given at 4.9%. All the patients ate egg whites
      with variations in the number of eggs per day as follows: less than one (3), one
      to two (56), three to four (14) and five to six (8). Over 70% were recommended by
      nurses to eat egg whites and about 63% of patients received other supplemental
      food. Some 44.1% of the patients who ate less than or equal to two eggs per day
      and 36.4% who ate more than two eggs per day developed grade 2-4 leukopenia, P =
      0.61. In conclusion, the data did not provide evidence in support of the
      conclusion that a greater egg white intake could significantly reduce the
      occurrence of leukopenia. 

PMID- 27039759
TI  - Social Determinants of Health and Tobacco Use in Five Low and Middle-Income
      Countries - Results from the Global Adult Tobacco Survey (GATS), 2011 - 2012.
AB  - BACKGROUND: Tobacco consumption continues to be the leading cause of preventable
      deaths globally. The objective of this study was to examine the associaton of
      selected socio-demographic variables with current tobacco use in five countries
      that participated in the Phase II Global Adult Tobacco Survey in 2011 - 2012.
      MATERIALS AND METHODS: We analysed internationally comparable representative
      household survey data from 33,482 respondents aged >= 15 years in Indonesia,
      Malaysia, Romania, Argentina and Nigeria for determinants of tobacco use within
      each country. Socio-demographic variables analysed included gender, age,
      residency, education, wealth index and awareness of smoking health consequences.
      Current tobacco use was defined as smoking or use of smokeless tobacco daily or
      occasionally. RESULTS: The overall prevalence of tobacco use varied from 5.5% in
      Nigeria to 35.7% in Indonesia and was significantly higher among males than
      females in all five countries. Odds ratios for current tobacco use were
      significantly higher among males for all countries [with the greatest odds among
      Indonesian men (OR=67.4, 95% CI: 51.2-88.7)] and among urban dwellers in Romania.
      The odds of current tobacco use decreased as age increased for all countries
      except Nigeria where. The reverse was true for Argentina and Nigeria. Significant
      trends for decreasing tobacco use with increasing educational levels and wealth
      index were seen in Indonesia, Malaysia and Romania. Significant negative
      associations between current tobacco use and awareness of adverse health
      consequences of smoking were found in all countries except Argentina.
      CONCLUSIONS: Males and the socially and economically disadvantaged populations
      are at the greatest risk of tobacco use. Tobacco control interventions maybe
      tailored to this segment of population and incorporate educational interventions
      to increase knowledge of adverse health consequences of smoking.

PMID- 27039760
TI  - Psychosocial Predictors of Breast Self-Examination among Female Students in
      Malaysia: A Study to Assess the Roles of Body Image, Self-efficacy and Perceived
      Barriers.
AB  - BACKGROUND: Early detection is a critical part of reducing the burden of breast
      cancer and breast selfexamination (BSE) has been found to be an especially
      important early detection strategy in low and middle income countries such as
      Malaysia. Although reports indicate that Malaysian women report an increase in
      BSE activity in recent years, additional research is needed to explore factors
      that may help to increase this behavior among Southeastern Asian women.
      OBJECTIVE: This study is the first of its kind to explore how the predicting
      variables of self-efficacy, perceived barriers, and body image factors correlate
      with self-reports of past BSE, and intention to conduct future breast self-exams
      among female students in Malaysia. MATERIALS AND METHODS: Through the analysis of
      data collected from a prior study of female students from nine Malaysian
      universities (n=842), this study found that self-efficacy, perceived barriers and
      specific body image sub-constructs (MBSRQ-Appearance Scales) were correlated
      with, and at times predicted, both the likelihood of past BSE and the intention
      to conduct breast self-exams in the future. RESULTS: Self-efficacy (SE)
      positively predicted the likelihood of past self-exam behavior, and intention to
      conduct future breast self-exams. Perceived barriers (BR) negatively predicted
      past behavior and future intention of breast self-exams. The body image sub
      constructs of appearance evaluation (AE) and overweight preoccupation (OWP)
      predicted the likelihood of past behavior but did not predict intention for
      future behavior. Appearance orientation (AO) had a somewhat opposite effect: AO
      did not correlate with or predict past behavior but did correlate with intention
      to conduct breast self-exams in the future. The body image sub-constructs of body
      area satisfaction (BASS) and self-classified weight (SCW) showed no correlation
      with the subjects' past breast self-exam behavior nor with their intention to
      conduct breast self-exams in the future. CONCLUSIONS: Findings from this study
      indicate that both self-efficacy and perceived barriers to BSE are significant
      psychosocial factors that influence BSE behavior. These results suggest that
      health promotion interventions that help enhance self-efficacy and reduce
      perceived barriers have the potential to increase the intentions of Malaysian
      women to perform breast self-exams, which can promote early detection of breast
      cancers. Future research should evaluate targeted communication interventions for
      addressing self-efficacy and perceived barriers to breast self-exams with at-risk
      Malaysian women. and further explore the relationship between BSE and body image.

PMID- 27039761
TI  - BRCA1 Gene Mutations and Influence of Chemotherapy on Autophagy and Apoptotic
      Mechanisms in Egyptian Breast Cancer Patients.
AB  - BACKGROUND: It is well established that mutations in the BRCA1 gene are a major
      risk factor for breast cancer. Induction of cancer cell death and inhibition of
      survival are the main principles of cancer therapy. In this context, autophagy
      may have dual roles in cancer, acting on the one hand as a tumor suppressor and
      on the other as a mechanism of cell survival that can promote the growth of
      established tumors. Therefore, understanding the role of autophagy in cancer
      treatment is critical. Moreover, defects in apoptosis, programmed cell death, may
      lead to increased resistance to chemotherapy. PURPOSE: The aim of the present
      study was to detect BRCA1 gene mutations in order to throw more light on their
      roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy
      and apoptosis in determining response to a fluorouracil, doxorubicin,
      cyclophosphamide (FAC) regimen was investigated. MATERIALS AND METHODS: Forty
      five female breast cancer cases and thirty apparently healthy females were
      enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1
      and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3
      were measured before and after chemotherapy. RESULTS: BRCA1 mutations were found
      in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most
      frequent being 5382insC followed by C61G and 185 delAG. The results revealed that
      chemotherapy caused elevation in serum concentration levels of the autophagic
      biomarkers (Beclin 1 and LC3). This elevation was associated with a significant
      decrease in serum concentration levels of Bcl-2 and significant increase in
      caspase-3 concentration levels (apoptotic markers). CONCLUSIONS: The results of
      the present study indicate a very high level of BRCA mutations in breast cancer
      cases in Egypt and point to involvement of autophagic and apoptotic machinery
      activation in response to FAC chemotherapy.

PMID- 27039762
TI  - GIS Database and Google Map of the Population at Risk of Cholangiocarcinoma in
      Mueang Yang District, Nakhon Ratchasima Province of Thailand.
AB  - Cholangiocarcinoma (CCA) is a serious problem in Thailand, particularly in the
      northeastern and northern regions. Database of population at risk are need
      required for monitoring, surveillance, home health care, and home visit.
      Therefore, this study aimed to develop a geographic information system (GIS)
      database and Google map of the population at risk of CCA in Mueang Yang district,
      Nakhon Ratchasima province, northeastern Thailand during June to October 2015.
      Populations at risk were screened using the Korat CCA verbal screening test
      (KCVST). Software included Microsoft Excel, ArcGIS, and Google Maps. The
      secondary data included the point of villages, sub-district boundaries, district
      boundaries, point of hospital in Mueang Yang district, used for created the
      spatial databese. The populations at risk for CCA and opisthorchiasis were used
      to create an arttribute database. Data were tranfered to WGS84 UTM ZONE 48. After
      the conversion, all of the data were imported into Google Earth using online web
      pages www.earthpoint.us. Some 222 from a 4,800 population at risk for CCA
      constituted a high risk group. Geo-visual display available at following
      www.google.com/maps/d/u/0/ edit?mid=zPxtcHv_iDLo.kvPpxl5mAs90 and hl=th. Geo
      visual display 5 layers including: layer 1, village location and number of the
      population at risk for CCA; layer 2, sub-district health promotion hospital in
      Mueang Yang district and number of opisthorchiasis; layer 3, sub-district
      district and the number of population at risk for CCA; layer 4, district hospital
      and the number of population at risk for CCA and number of opisthorchiasis; and
      layer 5, district and the number of population at risk for CCA and number of
      opisthorchiasis. This GIS database and Google map production process is suitable
      for further monitoring, surveillance, and home health care for CCA sufferers. 

PMID- 27039763
TI  - Why a Combination of WP 631 and Epo B is an Improvement on the Drugs Singly -
      Involvement in the Cell Cycle and Mitotic Slippage.
AB  - Our previous studies clearly demonstrated that a combination of WP 631 and Epo B
      has higher activity against ovarian cancer cells than either of these compounds
      used separately. In order to fully understand the exact mechanism of action in
      combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated
      three control points essential for WP 631 and Epo B action to determine which
      cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate
      activity. The effects of the drug on the cell cycle were measured based on the
      nuclear DNA content using flow cytometry. Expression of cell cycle-regulating
      genes was analyzed using real-time PCR. It was discovered that WP 631, at the
      tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused
      significant G2/M arrest, whereas the drug combination induced stronger apoptosis
      and lower mitotic arrest than Epo B alone. This is very important information
      from the point of view of the fight against cancer, as, while mitotic arrest in
      Epo B-treated cells could be overcame after DNA damage repair, apoptosis which
      occurs after mitotic slippage in combination-treated cells is irreversible. It
      clearly explains the higher activity of the drug combination in comparison to Epo
      B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit
      CDK1, which may be a promising strategy for ovarian cancer treatment in the
      future. The drug combination diminishes EpCAM and HMGB1 expression to a greater
      degree than either WP 631 and Epo B alone. Owing to the fact that the high
      expression of these two proteins is a poor prognostic factor for ovarian cancer,
      a decrease in their expression, observed in our studies, may result in improved
      efficacy of cancer therapy. The presented findings show that the combination of
      WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

PMID- 27039764
TI  - The Neutrophil to Lymphocyte Ratio is an Independent Prognostic Factor in
      Patients with Metastatic Gastric Cancer.
AB  - Inflammation can play an important role in cancer progression and the prognostic
      importance of neutrophil to lymphocyte ratio (NLR), a marker of inflammation, in
      cancer is a current investigation topic. In the present study, we aimed to
      determine whether there is a prognostic link between NLR and metastatic gastric
      cancer (mGC). A total of 143 patients from the Akdeniz University and Antalya
      Training and Research Hospital database were retrospectively analyzed. The median
      NLR value was 3.34. The median overall survival (OS) and median progression-free
      survival (PFS) were 11.6 and 7.9 months, respectively, in patients with NLR<3.34
      while these values were 8.3 and 6.2 months respectively in patients with NLR
      >3.34 (p<0.001 and p=0.011, respectively). Our study showed that increased NLR is
      an independent prognostic factor associated with short survival in patients with
      mGC. 

PMID- 27039765
TI  - Initial Report for the Radiation Effects Research Foundation F1 Mail Survey.
AB  - To study the full health effects of parental radiation exposure on the children
      of the atomic bomb survivors, the Radiation Effects Research Foundation developed
      a cohort of 76,814 children born to atomic bomb survivors (F1 generation) to
      assess cancer incidence and mortality from common adult diseases. In analyzing
      radiationassociated health information, it is important to be able to adjust for
      sociodemographic and lifestyle variations that may affect health. In order to
      gain this and other background information on the F1 cohort and to determine
      willingness to participate in a related clinical study, the F1 Mail Survey
      Questionnaire was designed with questions corresponding to relevant health,
      sociodemographic, and lifestyle indicators. Between the years 2000 and 2006, the
      survey was sent to a subset of the F1 Mortality Cohort. A total of 16,183 surveys
      were completed and returned: 10,980 surveys from Hiroshima residents and 5,203
      from Nagasaki residents. The response rate was 65.6%, varying somewhat across
      parental exposure category, city, gender, and year of birth. Differences in
      health and lifestyle were noted in several variables on comparison across city
      and gender. No major differences in health, lifestyle, sociodemographics, or
      disease were seen across parental exposure categories, though statistically
      significant tests for heterogeneity and linear trend revealed some possible
      changes with dose. The data described herein provide a foundation for studies in
      the future. 

PMID- 27039766
TI  - Protection against Whole Body gamma-Irradiation Induced Oxidative Stress and
      Clastogenic Damage in Mice by Ginger Essential Oil.
AB  - Radioprotective effects of ginger essential oil (GEO) on mortality, body weight
      alteration, hematological parameters, antioxidant status and chromosomal damage
      were studied in irradiated mice. Regression analysis of survival data in mice
      exposed to radiation yielded LD50/30 as 7.12 and 10.14 Gy for control
      (irradiation alone) and experimental (GEO-treated irradiated) mice, respectively,
      with a dose reduction factor (DRF) of 1.42. In mice exposed to whole-body gamma
      irradiation (6 Gy), GEO pre-treatment at 100 and 500 mg/kg b.wt (orally)
      significantly ameliorated decreased hematological and immunological parameters.
      Radiation induced reduction in intestinal tissue antioxidant enzyme levels such
      as superoxide dismutase, catalase, glutathione peroxidase and glutathione was
      also reversed following administration of GEO. Tissue architecture of small
      intestine which was damaged following irradiation was improved upon
      administration of GEO. Anticlastogenic effects of GEO were studied by micronuclei
      assay, chromosomal aberration and alkaline gel electrophoresis assay. GEO
      significantly decreased the formation of micronuclei, increased the P/N ratio,
      inhibited the formation of chromosomal aberrations and protected agaisnt cellular
      DNA damage in bone marrow cells as revealed by comet assay. These results are
      supportive of use of GEO as a potential radioprotective compound. 

PMID- 27039767
TI  - OrCanome: a Comprehensive Resource for Oral Cancer.
AB  - Oral cancer is one of the most prevalent cancers in India but the underlying
      mechanisms are minimally unraveled. Cancer research has immensely benefited from
      genome scale high throughput studies which have contributed to expanding the
      volume of data. Such datasets also exist for oral cancer genes but there has been
      no consolidated approach to integrate the data to reveal meaningful biological
      information. OrCanome is one of the largest and comprehensive, user-friendly
      databases of oral cancer. It features a compilation of over 900 genes
      dysregulated in oral cancer and provides detailed annotations of the genes,
      transcripts and proteins along with additional information encompassing
      expression, inhibitors, epitopes and pathways. The resource has been envisioned
      as a one-stop solution for genomic, transcriptomic and proteomic annotation of
      these genes and the integrated approach will facilitate the identification of
      potential biomarkers and therapeutic targets. 

PMID- 27039768
TI  - Levels of Depression and Anxiety Post-Mastectomy in Breast Cancer Patients at a
      Public Sector Hospital in Karachi.
AB  - BACKGROUND: There is a noticeable change in the approach with which women
      nowadays seek help for diseases like breast cancer, primarily due to awareness
      campaigns, but what happens after surgical procedures is of great significance
      too. This study focused on the several psychological connotations attached to
      mastectomy and how the patients cope. OBJECTIVE: To understand the pattern of
      anxiety and level of depression among Pakistani patients undergoing mastectomy.
      MATERIALS AND METHODS: The sample size consisted of 88 patients who had undergone
      mastectomy at the different surgical units of the Civil Hospital, Karachi, from
      January 2012- December 2014; The questionnaire was administered before they were
      discharged i.e. within 3 days of surgical procedures. The patients were asked if
      they were willing to participate in this study, those who agreed signed the
      consent form and then we preceded by asking questions with a standardized tool. A
      self made questionnaire was constructed keeping in mind the nature and
      specification of the disease, which consisted of 20 questions related to anxiety
      and depression, focusing on a mixture of psychological and physiological
      symptoms. RESULTS: There were a total of 88 patients out of which 36 (41%) were
      aged 51 to 60 years, 24 (27.2%) of the patients were in the age category of 41 to
      50 years, 17 aged 61 and above (19.3%) and only 11 (12.5%) 30-40 years of age,
      the youngest of all the age categories. The pattern of depression and anxiety was
      found to be similar among all age categories, severe depression and anxiety
      predominating over moderate level of such symptoms, with only relatively few
      patients sufering mild or no depression symptoms. CONCLUSIONS: It was concluded
      that going through mastectomy leads to moderate to severe levels of depression
      and anxiety, primarily because the females feel incomplete and insecure after
      losing a part of themselves.

PMID- 27039769
TI  - Inhibitory Effects of Gallic Acid Isolated from Caesalpinia mimosoides Lamk on
      Cholangiocarcinoma Cell Lines and Foodborne Pathogenic Bacteria.
AB  - Gallic acid was isolated from Caesalpinia mimosoides Lamk and the structure s
      identified based on spectroscopic analysis and comparison with authentic
      compound. In this study we compared the ability of natural gallic acid (nGA) and
      commercial gallic acid (cGA) to inhibit the proliferation of cholangiocarcinoma
      cell lines (M213, M214) and foodborne pathogenic bacteria (Salmonella spp. and
      Plesiomonas shigelloides). Both nGA and cGA had the same inhibitory effects on
      cell proliferation by inducing apoptosis of cholangiocarcinoma cell lines. In
      addition, nGA inhibited growth of foodborne pathogenic bacteria in the same
      manner as cGA. Our results suggest that nGA from Caesalpinia mimosoides Lamk is a
      potential anticancer and antibacterial compound. However, in vivo studies are
      needed to elucidate the specific mechanisms involved. 

PMID- 27039770
TI  - Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its
      Relation with Disease-free Survival.
AB  - BACKGROUND: Breast cancer prognosis is influenced by several histopathology and
      clinical factors including expression of Ki67 which may have a predictive role in
      lymph node negative breast cancer patients. The aim of this study was to assess
      Ki67 expression in breast cancers without axillary lymph node involvement and to
      evaluate its prognostic value with regard to disease-free survival. MATERIALS AND
      METHODS: Subjects were selected from non-metastatic invasive breast cancer
      patients who were referred to the oncology department of Ghaem hospital during 1
      April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry
      (IHC) and compared with clinicopathological features. The relation of Ki67
      expression with disease-free survival was also analysed. RESULTS: A total of 106
      women with a mean age of 49 were examined. Some 94.3% were classified as having
      invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis
      was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53
      expression was positive in 48.1% of the cases. According to the IHC results, only
      8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with
      a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005).
      After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most
      commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67
      positive. CONCLUSIONS: In our population Ki67 appeared to be an independent
      prognostic factor for three-year survival. However, we stress that a survival
      study with a bigger sample size would help to support this conclusion.

PMID- 27039771
TI  - Significance of Proliferation Markers and Prognostic Factors in Egyptian Patients
      with Multiple Myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is influenced by genetic and micro
      environmental changes. Malignant plasma cells produce an abnormal monoclonal
      immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate
      cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure
      of many organs. B cell activating factor (BAFF), IL6 and IL10 are known to
      influence the growth and survival of malignant clones. AIM: The objectives of the
      present study were to investigate the circulating levels of BAFF , IL-10 and IL
      6, correlate them with well-known parameters of disease activity in patients with
      MM, and to detect their impact on patients' survival. MATERIALS AND METHODS: This
      study was conducted on 89 newly diagnosed MM patients and seventy apparently
      healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by
      ELISA for both groups and survival analysis was performed for all patients.
      RESULTS: Studied markers were higher in the MM patients compared to the normal
      control subjects. Patients survival was improved by high serum BAFF levels.
      CONCLUSIONS: High levels of BAFF were found to improve patients' survival. BAFF
      and IL-6 can be considered probable diagnostic markers for MM.

PMID- 27039772
TI  - Outcomes of Metastatic Gestational Trophoblastic Neoplasia: Fourteen Year
      Experience from a Northern Thailand Tertiary Care Center.
AB  - Metastatic gestational trophoblastic neoplasia (GTN) is an uncommon cancer. The
      principal treatment consists of chemotherapy with or without surgery or
      radiotherapy. We here retrospectively reviewed the outcomes of metastatic GTN
      treated at our institute between January, 1999 and December, 2013. Sixty-three
      patients met the criteria. The median age was 30.0 years and almost 90% were
      referral cases. Nearly 40% of the studied patients presented with vaginal
      bleeding while 22.2% were asymptomatic. The most common antecedent pregnancy was
      hydatidiform mole (57.1%) followed by term pregnancy (20.6%). The median interval
      time from antecedent pregnancy to the development of GTN was three months and the
      median pretreatment B-hCG was 58,274 mIU/ ml. Stage III (74.6%) was the most
      common staging followed by stage IV (20.6%) and stage II (4.8%). The most
      frequent surgery was hysterectomy (31.7%). Thoracotomy and craniotomy were
      performed in three and two patients, respectively. The most common first line
      chemotherapy regimen was methotrexate and folinic acid (36.5%) followed by EMA
      (etoposide, methotrexate, actinomycin D) (34.9%), EMACO (etoposide, methotrexate,
      actinomycin D, cyclophosphamide, vincristine) (17.5%) with the remission rate of
      66.7%. Nearly one-third of the patients were given a subsequent chemotherapy
      regimen after failure with the first line therapy and showed a final response
      rate of 73.0%. However, in stage IV, the response to first line treatment was
      only 38.5%. In conclusion, the outcomes of metastatic GTN were poor especially
      with the higher stages. 

PMID- 27039773
TI  - Journey of the Human Papillomavirus (HPV) in a Developing Country over 5 Years
      (2010 - 2015).
AB  - Human papillomavirus (HPV) is a prevalent sexually transmitted infection with
      serious medical, sexual, and relationship consequences. HPV vaccine protection is
      available globally but unfortunately vaccine uptake is inconsistent everywhere.
      From this study, it was observed that the awareness of cervical cancer, HPV virus
      and HPV vaccination in Malaysia is high, at 83.1%, 73.9% and 73.3% of
      respondents, respectively. However, a considerably low percentage had undergone
      HPV vaccination (8.6%) compared to those who had experienced a Pap smear (32.9%).
      Awareness between cervical cancer and HPV virus and vaccination was low. Health
      care providers and the governing bodies have to play a vital role in
      disseminating holistic information on the vaccine and the importance of getting
      vaccinated to the public more vigorously in Malaysia. 

PMID- 27039774
TI  - Investigating the Frequency of the ERCC1 Gene C8092A Polymorphism in Iranian
      Patients with Advanced Gastric Cancer Receiving Platinum-based Chemotherapy.
AB  - BACKGROUND: Platinum compounds are the main drugs for treatment of advanced
      gastric cancer. Previous studies have shown that clinical outcome with platinum
      based compounds depends on ERCC1 polymorphisms. The aim of this study was to
      investigate the frequency of a common polymorphism of ERCC1 gene (C8092A) in
      Iranian patients with advanced gastric cancer receiving platinum chemotherapy.
      MATERIALS AND METHODS: Genetic analysis of the ERCC1 C8092A polymorphism was
      performed by the PCR - RFLP method using 50 paraffin-embedded tissue specimens.
      RESULTS: Of the 50 cases, 32% of individuals showed CC genotype, 24% of them had
      CA genotype and 44% of patients had AA genotype. CONCLUSIONS: Based on the
      results, using of platinum-based chemotherapy would be expected to be
      specifically beneficial in only 32% of patients.

PMID- 27039775
TI  - Prostatic Bleeding after Prostatic Biopsy Effects Oncological Outcomes with
      Laparoscopic Radical Prostatectomy.
AB  - BACKGROUND: We vigorously reviewed patients' operation record who had adhesion of
      the Denonvilliers' fascia and found out most of these patients had prostatic
      bleeding after prostatic gland biopsies. We examined the magnitude of prostatic
      bleeding and frequency after biopsies and the relationship with oncological
      outcomes. MATERIALS AND METHODS: A total of 285 patients were selected for the
      final analyses. Inclusion criteria were as follows: receiving MRI three weeks
      after biopsiesand laparoscopic radical prostatectomy within 300 days after
      biopsy. We divided the patients into two groups with (group A) or without (group
      B) prostatic bleeding. We examined the magnitude of prostatic bleeding after
      biopsies and the relationship with operation time (OT), positive surgical margin
      (PSM), biochemical recurrence (BCR) and other factors. Furthermore, we created a
      logistic-regression model to derive a propensity score for prostatic bleeding
      after biopsies, which included all patient and hospital characteristics as well
      as selected interaction terms, and we examined the relationship with PSM and BCR.
      RESULTS: In all patients, the OT in the group B was shorter than the group A (p <
      0.001). Prostatic bleeding was associated with PSM (p=0.000) and BCR (p=0.036).
      In this propensity-matched cohort, 11 of 116 patients in the group B had PSM as
      compared with 36 of 116 patients from group A (match-adjusted odds ratio, 4.30;
      95%CI confidence interval, 2.06 to 8.96; P=0.000). In addition, eight of 116
      patients in group B encountered BCR, as compared with 18 of 116 patients in group
      A (match-adjusted odds ratio, 2.48; 95%CI, 1.03 to 5.96; P=0.042). Kaplan-Meier
      analysis in the propensity matching cohort showed a significant biochemical
      recurrence-free survival advantage for being free of prostate bleeding after
      biopsies. CONCLUSIONS: Our findings in the present cohort should help equip
      surgeons to pay attention to careful excision especially for those who
      experienced deferred prostatic bleeding.

PMID- 27039776
TI  - Comparison of EMA,CEA, CD10 and Bcl-2 Biomarkers by Immunohistochemistry in
      Squamous Cell Carcinoma and Basal Cell Carcinoma of the Skin.
AB  - BACKGROUND: Basal and squamous cell carcinoma (BCC and SCC) are the most common
      skin cancers worldwide and distinction between the two may sometimes be very
      difficult in routine histopathology. The present study was aimed to evaluate a
      reliable diagnostic method for these cancers based on immunohistochemistry (IHC).
      MATERIALS AND METHODS: IHC was used with antibodies to Bcl-2, CD10, CEA, and EMA
      biomarkers, which despite non-specificity are easily available for detection of
      various types of tumors in pathology sections and can be used as a panel for
      differentiation. In this descriptive and analytic study, paraffin- embedded
      blocks of 29 SCC patients and 29 BCC patients were collected and sectioned for
      IHC staining. The results were analyzed by the STATA (version 8) statistical
      package using the Chi-square test. RESULTS: BCC patients were 100%, 75.8%, 0% and
      0% positive for Bcl-2, CD10, CEA and EMA markers, respectively, and for SCC
      patients were 3.5%, 0%, 34.5% and 82.7% positive, respectively. Using
      simultaneously Bcl-2 and CD10 as positive markers, detection of BCC with 88%
      accuracy and 100% specificity was possible, while application of CEA and EMA
      positivity could detect SCC with 67% accuracy and 100% specificity. CONCLUSIONS:
      SCC and BCC have different immunostaining profiles; therefore, Bcl-2, CD10, CEA
      and EMA markers can be helpful to distinguish between them.

PMID- 27039777
TI  - Mammographic Screening of Women Attending a Reference Service Center in Southern
      Brazil.
AB  - BACKGROUND: To investigate the prevalence of and factors associated with
      performance of annual mammography by women above 40 years of age. MATERIALS AND
      METHODS: This cross-sectional retrospective study was conducted at an oncology
      reference service in Southern Brazil from October 2013 to October 2014 with 525
      women aged 40 years or older. RESULTS: The prevalence of annual mammography was
      54.1%; annual mammographic screening was performed for women without private
      medical insurance, who were under hormone replacement therapy and who had used
      contraception in the past. An association was found between non-performance of
      breast clinical and self-examination and non-performance of mammographic
      screening. CONCLUSIONS: Use of mammography for breast cancer screening in the
      public health care setting proved to be accessible; nevertheless, the proportion
      of screened women was low, and they exhibited poor adherence to the basic
      measures of care recommended for breast assessment. Thus, control of breast
      cancer requires implementing actions targeting the population most vulnerable to
      non-adherence to screening in addition to continuously monitoring and assessing
      that population to reduce the prevalence of this disease.

PMID- 27039778
TI  - Breast Cancer in Iranian Woman: Incidence by Age Group, Morphology and Trends.
AB  - BACKGROUND: Breast cancer is the most common cancer and the first cause of cancer
      death in women worldwide, with infiltrating duct carcinoma as the most common
      morphology. This study aimed to investigate trend of breast cancer incidence by
      age groups and histological changes in Iranian women between 2003 and 2008.
      MATERIALS AND METHODS: This is analytic study, carried out based on re-analysis
      of the Cancer Registry Center report of health deputy for women's breast cancer
      in Iran during a 6-year period (2003-2008). Statistical analysis for incidence
      time trends and morphology change percentage carried out joinpoint regression
      analysis using the software Joinpoint Regression Program. RESULTS: A total of
      36,340 cases were reported for Iranian women in the six years. Analytical trend
      showed an increasing incidence trend with significant annual percentage change
      (APC) of 15.2 (CI: 11.6 to 18.8). The lowest and highest significant increased
      trend were related to age groups of 40 to 44 years and above 85 years,
      respectively; with APCs of 13.0 and 25.1, respectively. Of total cases, 78.7% of
      cases were infiltrating duct carcinoma, decreasing from 82.0% in 2003 to 76.6% in
      2008, which was significant with an APC equal to -1.76 (CI:-2.7 to -0.8).
      CONCLUSIONS: The incidence trend of breast cancer is rising in Iranian women. The
      highest incidence was observed in the age groups 45-65 and 80-85. In conclusion,
      to reduce breast cancer incidence and its burden, preventive and screening
      programs for breast cancer, especially in young women, are recommended in Iran.

PMID- 27039779
TI  - Incremental Expression of 14-3-3 Protein Beta/Alpha in Urine Correlates with
      Advanced Stage and Poor Survival in Patients with Clear Cell Renal Cell
      Carcinoma.
AB  - We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their
      diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC)
      and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients
      with AML and 24 healthy volunteers were assessed. We used an enzyme-linked
      immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in
      urine. Values were higher in patients with ccRCC than in those with AML and in
      healthy volunteers. High levels were associated with pathologic stage, lymph node
      status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein
      beta/alpha were significantly increased in patients with small-sized carcinoma,
      irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in
      patients with AML. This study is the first to report that increased expression of
      14-3- 3 protein beta/alpha in urine is associated with advanced stage and poor
      survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha
      may differentiate AML from RCC, even when small sized. These results suggest that
      examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and
      prognostic marker in patients with ccRCC. 

PMID- 27039780
TI  - Assessing the EORTC QLQ-BM22 Module Using Rasch Modeling and Confirmatory Factor
      Analysis across Countries: a Comprehensive Psychometric Evaluation in Patients
      with Bone Metastases.
AB  - BACKGROUND: The European Organisation for Research and Treatment of Cancer
      Quality of Life Questionnaire Bone Metastases Module (EORTC QLQ-BM22) is a
      recently designed supplement to EORTC Quality of Life Questionnaire-C30 (EORTC
      QLQ-C30). Additional psychometric properties, especially using confirmatory
      factor analysis (CFA) and the Rasch model, are warranted. MATERIALS AND METHODS:
      A total of 573 patients with bone metastases were enrolled from eight countries
      with a mean+/-SD age of 55.8+/-13.7 years. Slightly more than two thirds of them
      were female (n=383; 66.8%). CFA was used to examine the BM22 framework; Rasch
      models were applied to understand misfit items and differential item functioning
      (DIF). RESULTS: The fit indices were satisfactory in CFA (comparative fit
      index=0.972, Tucker-Lewis index=0.964, root mean square error of
      approximation=0.076, and standardized root mean square residual=0.045). All items
      fit well in the Rasch models (mean square values were between 0.5 and 1.5), and
      only one item (number 17) displayed DIF across gender. However, there were six
      DIF items across Canada and Taiwan, ten across Canada and Iran, and six across
      Taiwan and Iran. CONCLUSIONS: The BM22 has satisfactory psychometric properties,
      and could assess the QoL of patients with bone metastases specifically focusing
      on their symptoms. Clinicians may want to use it to capture the underlying QoL
      for patients with bone metastases. However, the score of item 17 should be
      interpreted with caution when comparing male and female patients. In addition,
      researchers should note that variation in DIF items may occur when conducting an
      international study.

PMID- 27039781
TI  - Eosinophilia in Pleural Effusions: a Speculative Negative Predictor for
      Malignancy.
AB  - BACKGROUND: Eosinophilic pleural effusion (EPE) is an eosinophil count more than
      10% on cytology of pleural samples. Recently, it was reported that malignancy had
      been the most prevalent cause inducing EPE. Therefore, we conducted an analysis
      on the prevalence and etiology of EPE and investigated the relationship between
      EPE and malignancy. MATERIALS AND METHODS: Data for pleural cell differential
      count from patients receiving thoracentesis during the period from January 2008
      to December 2013 were compared with clinical data and established diagnosis of
      patients obtained via electronic chart review. RESULTS: A total of 6,801 requests
      of pleural cytology from 3,942 patients with pleural effusion who had received
      thoracentesis were available at Far Eastern Memorial Hospital from 2008 to 2013,
      and of these subjects, 115 (2.9%) were found to have EPE. The most frequent cause
      of EPE was malignancy (33.0%, n=38), followed by parapneumonic effusions (27.8%,
      n=32), tuberculosis pleuritis (13.9%, n=16), transudate effusions (12.2%, n=14)
      and the presence of blood or air in pleural space (10.4%, n=12). Additionally, an
      inverse relationship of eosinophilia in pleural fluid was identified in patients
      with malignancy and EPE. The cut-off eosinophil count in pleural fluid was 15%
      for the most accurate discrimination between malignancy and benign disorders in
      patients with EPE. At the cut-off level, the sensitivity and specificity were
      65.8% and 67.5%, respectively. CONCLUSIONS: Pleural fluid eosinophilia was a
      speculative negative predictor for malignancy, despite the fact that cancers,
      including lung cancers and metastatic cancers to lung, were the most leading
      cause of pleural fluid eosinophilia. An inverse correlation was observed between
      the pleural eosinophil percentage and the likelihood of malignancy in patients
      with EPE.

PMID- 27039782
TI  - Squamous Cell Carcinoma as the Most Common Lesion of the Tongue in Iranians: a 22
      Year Retrospective Study.
AB  - The tongue has been globally considered as an indicator of general health for
      millennia. This study aimed to determine the prevalence and distribution of
      tongue lesions in an Iranian population. In this retrospective study, data from
      6,435 oral biopsy reports over a 22-year period (1992-2014) were retrieved from
      archives of Oral and Maxillofacial Pathology Department, Shahid Beheshti Dental
      School, Tehran, Iran. These reports were analyzed according to age, sex, type of
      lesion and location. Prevalence of tongue lesions were reported as percentages.
      Out of total oral lesions, 238 (3.7%) were found in the tongue, with the
      incidence peak (42%) being between 41-60 years. Men constituted 53% and women
      47%of patients. The youngest patient was a 3-year-old girl with pyogenic
      granuloma and the oldest one was a 93-year-old man with squamous cell carcinoma
      (SCC). SCC was the most common (25%) lesion generally found in the lateral border
      of the tongue with a male predilection. The second and third most prevalent
      lesions of the tongue were benign keratosis (frictional keratosis) (13.4%) and
      leukoplakia (13%).White-red lesions (38.6%) were the most frequent subgroup
      followed by neoplastic lesions (28%). Moreover, irritation fibroma, non-specific
      ulcers, squamous papilloma, and hemangioma were found as the most frequent
      lesions in their related subgroups.Given the high rate of SCC of the tongue in
      Iranian patients, this area should be examined more carefully by dental
      practitioners and physicians. 

PMID- 27039783
TI  - Time Trend Analysis of Oral Cancer in Iran from 2005 to 2010.
AB  - BACKGROUND: There is a considerable lack of understanding of oral cancer
      incidence, especially its time trend in Iran. In this study, the authors aimed to
      analyze time trend of oral cancer incidence with a focus on differences by gender
      in a period of six years - from 2005 to 2010. MATERIALS AND METHODS: Both
      population-based cancer registry and national cancer registry (NCR) data based on
      pathologic reports from 2005 to 2010 were obtained from the Ministry of Health
      and Medical Education (MOHME). Population data were also received from
      Statistical Centre of Iran. Age-standardized incidence rates (ASRs) based on the
      World Standard Population were then calculated. Finally, Negative Binomial
      regression was run for time trend analysis. RESULTS: The maximum ASR for males
      was calculated as 2.5 per 100,000 person-years in 2008 and the minimum was
      observed as 1.9 per 100,000 person-years in 2005 and 2006. Meanwhile, the maximum
      ASR for females was estimated as 1.8 per 100,000 person-years in 2009 and the
      minimum was calculated as 1.6 per 100,000 person-years in 2005 and 2006.
      Additionally, in females, incidence risk ratio (IRR) did not show a clear
      decreasing or increasing trend during the six years. Nevertheless, in males an
      increasing trend was observed. The maximum IRR adjusted for age group and
      province, for females was reported in 2009 (IRR=1.05 95% CI: 0.90-1.23), and for
      males was estimated in 2010 (IRR=1/2 95% CI: 1.04 - 1.38). CONCLUSIONS: Our
      findings highlight disparities between oral cancer incidence trends in males and
      females over the six years from 2005 to 2010.

PMID- 27039784
TI  - Impact of Peri-Operative Anemia and Blood Transfusions in Patients with Gastric
      Cancer Receiving Gastrectomy.
AB  - BACKGROUND: Potential disadvantages of blood transfusion during curative
      gastrectomy for gastric cancer have been reported, and the role of peri-operative
      transfusions remains to be ascertained. Thus, the aim of our study was to survey
      its impact in patients with gastric cancer undergoinging gastrectomy. MATERIALS
      AND METHODS: Clinical data of patients receiving curative gastrectomy at Far
      Eastern Memorial Hospital were obtained. Findings for pre-operative anemia
      states, pre-, peri- and post-operative transfusion of red blood cell (RBC)
      products as well as post-operative complication events were collected for
      univariate analysis. RESULTS: A total of 116 patients with gastric cancer
      received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre
      operative and intra- and post-operative transfusion of RBC products were markedly
      associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58,
      P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri-
      and post-operative RBC transfusion was significantly associated with prolonged
      hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002)
      and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001).
      Also, the overall survival was seemingly decreased by peri-operative RBC
      transfusion in our gastric cancer cases (P=0.078). CONCLUSIONS: Our survey
      indicated that peri-operative RBC transfusion could increase the risk of
      infectious events and acute renal failure post curative gastrectomy as well as
      worsen the overall survival in gastric cancer cases. Hence, unnecessary blood
      transfusion before, during and after curative gastrectomy should be avoided in
      patients with gastric cancer.

PMID- 27039785
TI  - Distribution of the Population at Risk of Cholangiocarcinoma in Bua Yai District,
      Nakhon Ratchasima of Thailand Using Google Map.
AB  - BACKGROUND: Cholangiocarcinoma (CCA), a major problem of health in Thailand,
      particularly in Northeastern and Northern regions, is generally incurable and
      rapidly lethal because of presentation in stage 3 or 4. Early diagnosis of stage
      1 and 2 could allow better survival. Therefore, this study aimed to provide a
      distribution map of populations at risk for CCA in BuaYai district of Nakhon
      Ratchasima province, Northeast Thailand. MATERIALS AND METHODS: A cross-sectional
      survey was carried out in 10 sub-districts and 122 villages, during June and
      November 2015. The populations at risk for CCA were screened using the Korat CCA
      verbal screening test (KCVST) and then risk areas were displayed by using Google
      map (GM). RESULTS: A total of 11,435 individuals from a 26,198 population
      completed the KCVST. The majority had a low score of risk for CCA (1-4 points;
      93.3%). High scores with 6, 7 and 8 points accounted for 1.20%, 0.13% and 0.02%.
      The population at risk was found frequently in sub-district municipalities,
      followed by sub-district administrative organization and town municipalities,
      (F=396.220, P-value=0.000). Distribution mapping comprised 11 layers: 1,
      district; 2, local administrative organization; 3, hospital; 4, KCVST
      opisthorchiasis; 5, KCVST praziquantel used; 6, KCVST cholelithiasis; 7, KCVST
      raw fish consumption; 8, KCVST alcohol consumption; 9, KCVST pesticide used; 10,
      KCVST relative family with CCA; and 11, KCVST naive northeastern people.
      Geovisual display is now available online. CONCLUSIONS: This study indicated that
      the population at high risk of CCA in Bua Yai district is low, therefore setting
      a zero model project is possible. Key success factors for disease prevention and
      control need further study. GM production is suitable for further CCA
      surveillance and monitoring of the population with a high risk score in this
      area.

PMID- 27039786
TI  - Weight Gain and Alcohol Drinking Associations with Breast Cancer Risk in Japanese
      Postmenopausal Women - Results from the Japan Collaborative Cohort (JACC) Study.
AB  - BACKGROUND: We investigated four factors, height, weight gain since age 20,
      physical activity, and alcohol drinking, for associations with risk of breast
      cancer (BC) according to menopausal status, using the latest data of the Japan
      Collaborative Cohort Study (JACC Study). MATERIALS AND METHODS: We confined the
      analysis to 24 areas available of cancer incidence information, excluding women
      with a previous diagnosis of BC. Baseline data were collected from 38,610 (9,367
      premenopausal, and 29,243 postmenopausal) women during 1988 and 1990. The study
      subjects were followed-up at the end of 2009, and 273 (84 premenopausal, and 189
      postmenopausal) cases of BC were newly diagnosed in 501,907 person-years. The Cox
      model was used to estimate a hazards ratio (HR) and its 95% confidence interval
      (CI) of BC risk. RESULTS: As a result of the multivariate analysis adjusting for
      age at baseline survey, age at menarche, number of live births, and, age at first
      delivery, weight gain since age 20 of 6.7 kg-9.9 kg, and >=10.0 kg were
      significantly associated with increased risk for postmenopausal BC (HR=2.48, 95%
      CI 1.40-4.41, and, HR=2.94, 95% CI 1.84-4.70, respectively). Significantly
      increased trend of BC risk was also observed in weight gain since age 20 (p for
      trend, p<0.001). Amount of ethanol intake per day>=15.0 g was significantly
      associated with increased risk for postmenopausal BC in the multivariable
      adjusted analysis (HR=2.74, 95% CI 1.32-5.70). CONCLUSIONS: Higher weight gain in
      adulthood and larger amounts of ethanol intake were significantly associated with
      increased risk of BC in Japanese postmenopausal women. None of the investigated
      factors were significantly associated with BC risk in Japanese premenopausal
      women.

PMID- 27039787
TI  - Investigating Preoperative Hematologic Markers for Prediction of Ovarian Cancer
      Surgical Outcome.
AB  - PURPOSE: The current study aimed at assessing the association between neutrophil
      lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) for the prognosis of
      the surgical outcome of epithelial ovarian cancer (EOC). MATERIALS AND METHODS:
      EOC patient medical records of surgical operations between January, 2005 and
      December, 2015 were reviewed and their data of clinicopathological complete blood
      counts (CBCs) and surgical outcomes were collected. To assess their effects on
      surgical outcomes, PLR and NLR optimal predictive values were determined and then
      compared with each other. RESULTS: A statistically significant relation was found
      between surgical outcomes and NLR and PLR (p<0.001 and p<0.001), for which new
      cutoff points were gained (PLR: 192,3,293; NLR: 3). The sensitivity and
      specificity were 0.74 and 0.67, respectively for PLR and 0.74 and 0.58, for NLR.
      CONCLUSIONS: NLR and PLR seem to be useful methods for the prediction of surgical
      outcomes in patients with EOCs. Increased NLR and PLR proved to be beneficial for
      poor surgical outcomes. Moreover, PLR increase showed further help in the
      predicting outcome of EOC suboptimal debulking.

PMID- 27039788
TI  - Treatment Outcome and Predictors of Survival in Thai Adult Rhabdomyosarcoma
      Cases.
AB  - BACKGROUND: Adult rhabdomyosarcoma (RMS) is a rare and aggressive disease with
      limited data compared with pediatric RMS. The goal of this study was to determine
      the treatment outcome and identify factors related to survival outcome in
      Thailand. MATERIALS AND METHODS: Adult patients (>=15 years old) with the
      pathological diagnosis of RMS between 1985 and 2010 were reviewed. The data were
      retrospectively reviewed from the pathological results and medical records from
      Srinagarind Hospital, Khon Kaen University. RESULTS: A total of 34 patients were
      identified in the study. The median age at diagnosis was 35.5 years and the most
      common primary sites were extremity and the head and neck region. The incidence
      of pleomorphic RMS increased with age and none was found in those aged younger
      than 20 years old. The median survival time was 9.33 months (95%CI: 5.6-13.1).
      The 1- and 5- year survival rates were 38.2% (22.3-54.0) and 20.6% (9.1-35.3). On
      multivariate analysis, age and size of tumor did not predict better outcome while
      chemotherapy and surgery were significantly associated with longer survival.
      CONCLUSIONS: Outcome of adult RMS was poor. Surgery and chemotherapy are s
      trongly associated with better prognosis and multimodality treatment should be
      incorporated in the clinic.

PMID- 27039789
TI  - Mate Intake and Risk of Breast Cancer in Uruguay: a Case- Control Study.
AB  - Regarding 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage
      in temperate South American regions), most epidemiologic studies showed positive
      associations with risk of some cancers, (e.g. upper aerodigestive tract), but
      evidence on breast cancer (BC) risk is limited to a previous multi-site study,
      which reported a non significant odds ratio [OR]=0.85, 95% confidence interval
      [95% CI] 0.67-1.09, p for trend=0.31) for the highest quartile of intake. The
      present study was conducted in order to further assess associations of 'mate'
      intake with BC risk. We combined two databases of women belonging to public and
      private healthcare hospitals. The sample included 572 BC incident cases and 889
      controls interviewed with a specific questionnaire featured by socio-demographic,
      reproductive and lifestyle variables, and a food frequency questionnaire of 64
      items, also analyzing 'mate' intake (consumer status, daily intake, age at start,
      age at quit, duration of habit, intensity of intake). ORs and their 95%CI were
      calculated through unconditional logistic regression, adjusting for relevant
      potential confounders. The highest quartile of 'mate' intake was inversely
      associated with BC risk (OR=0.40, 95%CI 0.26-0.57, p for trend <0.001).
      Stratified analyses also displayed strong significant inverse associations for
      'mate' in frequent tea drinkers (OR=0.22), high energy intake (OR=0.23), high
      body mass index (OR=0.29) and in postmenopausal women (OR=0.36), among other
      results. As conclusions, we found evidence of a significant inverse association
      for 'mate' intake and BC risk. 

PMID- 27039790
TI  - Breast Cancer Knowledge, Perception and Breast Self- Examination Practices among
      Yemeni Women: an Application of the Health Belief Model.
AB  - BACKGROUND: The incidence of breast cancer is rapidly increasing in Yemen with
      recent indications of constituting one-third of female cancers. The main problem
      in Yemen remains very late presentation of breast cancer, most of which should
      have been easily recognisable. Since stage of disease at diagnosis is the most
      important prognostic variable, early diagnosis is an important option to be
      considered for control of breast cancer in low resourced settings like Yemen. In
      the present study, we aimed at describing breast cancer knowledge, perceptions
      and breast self-examination (BSE) practices among a sample of Yemeni women.
      MATERIALS AND METHODS: This cross-sectional study covered 400 women attending
      four reproductive health centres in Aden, Yemen through face-to-face interview
      using a structured questionnaire during April - July 2014. We collected data on
      sociodemographic characteristics, knowledge about breast cancer, and screening
      practices as well as respondents' perceptions based on the five sub scales of the
      Health Belief Model (HBM): perceived susceptibility; perceived severity;
      perceived barriers; perceived benefits; and self-efficacy. The response format
      was a fivepoint Likert scale. Statistical Package for Social Sciences (SPSS 20)
      was used for statistical analysis. Statistical significance was set at p<0.05.
      Logistic regression analysis was conducted with BSE as a dependent variable.
      RESULTS: The mean age of women was 26.5 (S.D=5.6) years. The majority (89.0%) had
      never ever performed any screening. Two-thirds of respondents had poor knowledge.
      Perceived BSE benefits and self-efficacy and lower BSE barriers perception were
      significant independent predictors of BSE practice. CONCLUSIONS: Poor knowledge
      and inadequate BSE practices are prevailing in Yemen. The need for implementing
      culturally sensitive targeted education measures is mandatory in the effort to
      improve early detection and reduce the burden of breast cancer.

PMID- 27039791
TI  - Missing Elements in Surgical Pathology Reports: Breast, Colon and Stomach
      Cancers.
AB  - Cancer pathology reports play an important role in choice of patient care. They
      provide crucial information concerning diagnosis, therapy options, and prognosis.
      Professional pathology institutions, such as the College of American Pathologists
      (CAP), have developed checklists to ensure the presence of all the required
      elements in reports. In this study, 438 surgical pathology reports of patients
      with breast (148), colon (147), and stomach cancer (143) were evaluated with
      respect to the presence of mandated elements according to CAP checklists. The
      most common missing element in all the three types of cancer was 'staging' (73.6,
      53.1, and 56.6% in breast, colon, and stomach cancer reports missed 'staging',
      respectively). The second most missing element was 'tumor site' in breast (64.2%)
      and stomach cancer (30.1%), and 'procedure' in colon cancer (29.3%). 'Perineural
      invasion' was the third most missing element in the three types of cancer (25.7,
      17.0, and 22.4% in breast, colon, and stomach cancer, respectively). Only 11.4%
      of reports included all key elements required by CAP. The use of checklists was
      associated with higher rate of completeness. This study demonstrates that the key
      elements requiring the information on the requisition forms from the clinicians
      are commonly missed, leading to ambiguity. 

PMID- 27039792
TI  - Prevalence of Cigarette Smoking and Associated Factors among Male Citizens in
      Tehran, Iran.
AB  - BACKGROUND: Cigarette smoking is as the leading cause of cancer mortality and
      other chronic diseases in males worldwide. The prevalence of cigarette smoking is
      different across and within countries by age, education level, occupation, and so
      on. This study aimed to determine the prevalence of cigarette smoking and its
      relationship with individuals' demographic factors and BMI in adolescent men
      living in Tehran, Iran. MATERIALS AND METHODS: This study involved secondary
      analysis of the 'Urban Health Equity Assessment and Response Tool-2' survey
      conducted in Tehran, Iran, among men aged 20+, 2011-2012. Using a multistage
      sampling method, 45,990 men were included in the study. The cigarette smoking
      status, BMI and demographic factors measured through a self-administered
      questionnaire. Chi-square, t-test, and logistic regression model were used to
      examine the relationships between the independents variables and cigarette
      smoking behavior, using SPSS software version 21. RESULTS: In the total of 45,990
      men, the overall prevalence of cigarette smoking was 14.6% (CI 95%: 14.29-
      14.94). Age (OR=0.96; CI 95%:0.94-0.98), house ownership (OR=0.68; CI 95%: 0.64
      0.72), job status (OR=0.60; CI 95%: 0.46-0.86), marital status (OR=0.42; CI 95%:
      0.39-0.47) and educational levels (OR=0.50; CI95%: 0.45-0.54) were associated
      with the prevalence of cigarette smoking. However, associations with BMI, family
      size, residency years, and district were not statistically significant.
      CONCLUSIONS: Given the relatively high prevalence of cigarette smoking in the
      study population, policy interventions are required to address this major public
      health issue, with a focus on the population demographic influences.

PMID- 27039793
TI  - Determination of Patient Learning Needs after Thyroidectomy.
AB  - The purpose of this study was to determine discharge learning needs of patients
      undergoing thyroidectomy. The population of this descriptive study consisted of
      patients undergoing thyroidectomy in the Endocrine Surgery Unit of a university
      hospital between February and December 2013. The study included 251 patients who
      were discharged after thyroidectomy. Data obtained using the data collection form
      and the Patient Leaning Needs Scale (PLNS) were analyzed by frequency, mean,
      standard deviation, Kruskal Wallis and student-t tests. The mean age of the
      patients was 47.91+/-13.05 and 76.1% were females. The PLNS total mean score was
      208.38+/-34.91, with the maximum score of 39.23+/-6.80 on the subscale of
      treatment and complications and the minimum score of 19.45+/-4.70 on the subscale
      of feelings related to condition. It was found that the PLNS total score of the
      patients was not influenced by age, gender, marital status (p>0.05). This study
      demonstrated that patients had high learning needs after thyroidectomy. 

PMID- 27039794
TI  - Frequency of Cholelithiasis and Biliary Pathology in the Easter Island Rapanui
      and Non-Rapanui Populations.
AB  - BACKGROUND: Chile is one of the countries with the highest prevalence of
      cholelithiasis worldwide, considering the Mapuche ethnicity as a risk factor for
      developing this pathology. Moreover, cholelithiasis is the main risk factor for
      developing gallbladder cancer, being the fifth cause of cancer death in Chile.
      The purpose of this study was to compare the frequency of cholelithiasis and
      biliary pathology among the population belonging to Rapanui ethnicity and non
      Rapanui population living on Easter Island. MATERIALS AND METHODS: In this
      retrospective case-control study, a total of 609 abdominal ultrasonographs
      performed consecutively in Hanga Roa Hospital during the period August 2012 to
      January 2015 were analyzed. Multiple logistic regression was used to obtain odds
      ratio (OR) and 95% confidence intervals (95% CI) of cholelithiasis and biliary
      pathology, adjusting for age, gender and referral diagnostic hypothesis. RESULTS:
      In the Rapanui population the frequency for cholelithiasis and biliary pathology
      was 6.4% and 13%, meanwhile for the non-Rapanui population it was 13% and 22%
      respectively. Compared to the non-Rapanui Chilean population, the Rapanui
      ethnicity presented an OR of 0.53 (95% CI: 0.29-0.95) for cholelithiasis and OR
      of 0.52 (95% CI: 0.33-0.82) for biliary pathology. CONCLUSIONS: We found
      statistically significant ethnic differences in the frequency of cholelithiasis
      and biliary disease among the population of Rapanui and non-Rapanui ethnicity, so
      that this could be a protective factor for the development of biliary pathology,
      given the Chilean population context. Other studies including community
      population to determine the real prevalence of cholelithiasis and analyze the
      protective role of Rapanui ethnicity on this disease are necessary.

PMID- 27039795
TI  - Association of Serum HE4 with Primary Tumor Diameter and Depth of Myometrial
      Invasion in Endometrial Cancer Patients at Rajavithi Hospital.
AB  - BACKGROUND: Although there are no biomarkers that are routinely used in
      endometrial cancer (EC) management, many studies have found that serum human
      epididymis protein 4 (HE4) is superior to cancer antigen 125 (CA125) in the
      detection of EC. The correlation of HE4 with two prognostic factors for EC,
      primary tumor diameter (PTD) and depth of myometrial invasion (DMI) may be useful
      in identifying EC patients at high risk of lymphatic dissemination. OBJECTIVE: To
      evaluate the correlation of serum HE4 with PTD and DMI in patients with EC.
      MATERIALS AND METHODS: A cross-sectional study was conducted on 70 EC patients
      who were scheduled for elective surgery at Rajavithi Hospital between 1st
      September 2013 and 30th May 2014. Preoperative serum levels of HE4 and CA125 were
      investigated, and then gross measurement of PTD was taken and postoperative
      pathologic slides were reviewed for DMI including histologic types, grading and
      staging. RESULTS: Preoperative serum HE4 levels were strongly correlated with PTD
      (r=0.65, p<0.001) and moderately correlated with DMI (r=0.46, p<0.001). Moreover,
      serum HE4 levels were significantly elevated in EC patients with PTD >2 cm
      (p<0.001) and DMI > 50% (p=0.004). The performance of serum HE4 in identifying EC
      patients at low risk and high risk of lymph node metastasis was significantly
      better than that of CA125 (AUC 0.88 vs. 0.65, p=0.003). At an optimal cut-off
      value of 70 pM/L, serum HE4 had a sensitivity of 83.3% and a specificity of
      80.0%. CONCLUSIONS: In EC patients, preoperative serum HE4 is significantly
      correlated with PTD and DMI. Serum HE4 levels could be useful in identifying
      endometrial cancer patients at high risk of lymphatic spread who would benefit
      from systemic lymphadenectomy at the cut-off value of 70 pM/L.

PMID- 27039797
TI  - Molecular Mechanism of Crocin Induced Caspase Mediated MCF-7 Cell Death: In Vivo
      Toxicity Profiling and Ex Vivo Macrophage Activation.
AB  - BACKGROUND: Crocus sativus and its major constituent crocin are well established
      to have anti-cancer properties in breast cancer cells (MCF-7). However the role
      of C. sativus extract (CSE) and crocin on caspase signaling mediated MCF-7 cell
      death at molecular level is remains unclear. In this study, we tried to unravel
      role of CSE and crocin on caspase mediated MCF-7 cells death and their in vivo
      preclinical toxicity profiling and immune stimulatory effect. MATERIALS AND
      METHODS: CSE extract was fractionated by HPLC and crocin was isolated and
      characterized by NMR, IR, and MS. MCF-7 cells were treated with both CSE and
      crocin and expression of Bcl-2 and Bax was assessed after 24 and 36 hours.
      Furthermore, caspase 3, caspase 8 and caspase 9 expression was determined by
      Western blotting after 24 hours of treatment. DNA fragmentation analysis was
      performed for genotoxicity of CSE and crocin in MCF-7 cells. The in vivo toxicity
      profile of CSE (300 mg/kg of b.wt) was investigated in normal Swiss albino mice.
      In addition, peritoneal macrophages were collected from crocin (1, 1.5 and 2
      mg/kg body weight) treated mice and analyzed for ex vivo yeast phagocytosis.
      RESULTS: Immunoblot analysis revealed that there was time dependent decline in
      anti-apoptotic Bcl-2 with simultaneous upregulation of Bax in CSE and crocin
      treated MCF-7 cells. Further CSE and crocin treatment downregulated caspase 8 and
      9 and cleaved the caspase 3 after 24 hours. Both CSE and crocin elicited
      considerable DNA damage in MCF-7 cells at each concentration tested. In vivo
      toxicity profile by histological studies revealed no observable histopathologic
      differences in the liver, kidney, spleen, lungs and heart in CSE treated and
      untreated groups. Crocin treatment elicited significant dose and time dependent
      ex vivo yeast phagocytosis by peritoneal macrophages. CONCLUSIONS: Our study
      delineated involvement of pro-apoptotic and caspase mediated MCF-7 cell death by
      CSE and crocin at the molecular level accompanied with extensive DNA damage.
      Further we found that normal swiss albino mice can tolerate the maximum dose of
      CSE. Crocin enhanced ex vivo macrophage yeast phagocytic ability.

PMID- 27039796
TI  - Breast Cancer Trend in Iran from 2000 to 2009 and Prediction till 2020 using a
      Trend Analysis Method.
AB  - BACKGROUND: Breast cancer is the most common cancer in women worldwide with a
      rising incidence rate in most countries. Considering the increase in life
      expectancy and change in lifestyle of Iranian women, this study investigated the
      age-adjusted trend of breast cancer incidence during 2000-2009 and predicted its
      incidence to 2020. MATERIALS AND METHODS: The 1997 and 2006 census results were
      used for the projection of female population by age through the cohort-component
      method over the studied years. Data from the Iranian cancer registration system
      were used to calculate the annual incidence rate of breast cancer. The age
      adjusted incidence rate was then calculated using the WHO standard population
      distribution. The five-year-age-specific incidence rates were also obtained for
      each year and future incidence was determined using the trend analysis method.
      Annual percentage change (APC) was calculated through the joinpoint regression
      method. RESULTS: The bias adjusted incidence rate of breast cancer increased from
      16.7 per 100,000 women in 2000 to 33.6 per 100,000 women in 2009. The incidence
      of breast cancer had a growing trend in almost all age groups above 30 years over
      the studied years. In this period, the age groups of 45-65 years had the highest
      incidence. Investigation into the joinpoint curve showed that the curve had a
      steep slope with an APC of 23.4% before the first joinpoint, but became milder
      after this. From 2005 to 2009, the APC was calculated as 2.7%, through which the
      incidence of breast cancer in 2020 was predicted as 63.0 per 100,000 women.
      CONCLUSIONS: The age-adjusted incidence rate of breast cancer continues to
      increas in Iranian women. It is predicted that this trend will continue until
      2020. Therefore, it seems necessary to prioritize the prevention, control and
      care for breast cancer in Iran.

PMID- 27039798
TI  - Hormone Use is Associated with Lymphovascular Invasion in Breast Cancer.
AB  - BACKGROUND: Risk of developing breast cancer increases with short breastfeeding
      and the use of hormones. The prognosis of breast cancer is better if the tumours
      are hormone receptor positive. Since breast feeding affects estrogen and
      progesterone receptors, we wanted to investigate how such reproductive factors as
      breastfeeding and the use of hormones interact with known prognostic markers and
      specific tumour characteristics in women with breast cancer. MATERIALS AND
      METHODS: A total of 250 women treated for breast cancer from a larger cohort
      completed a questionnaire on breastfeeding, number and age at births and use of
      hormones. A logistic regression analysis was made to search for connections
      between known prognostic markers on the one hand (type of cancer, grade, tumor
      size, estrogen receptor and progesterone receptor, lymphovascular invasion and
      DNA-ploidy) and reproductive data, breastfeeding, and hormone use on the other.
      RESULTS AND CONCLUSIONS: Hormone use, but not breastfeeding, was significantly
      associated, also on multivariate analysis, with the prognostic variable
      lymphovascular invasion, connected to a worse prognosis. No other hormone use or
      breast feeding correlations with prognostic variables were found.

PMID- 27039799
TI  - Phase III of Study of R-CHOP-21 vs R-CHOP-14 for Untreated Stage III and IV B
      cell Non-Hodgkin's Lymphoma: a Report from Iran.
AB  - BACKGROUND: A combination of rituximab to cyclophosphamide, doxorubicin,
      vincristine, and prednisone (R-CHOP) is one of the most effective front-line
      therapies to treat B-cell non-Hodgkin's lymphoma (NHL). The aim of this trial was
      to evaluate overall survival (OS), progression free survival (PFS) and toxicity
      of R-CHOP-14 compared to R-CHOP-21 in untreated stage III and IV B-cell NHL
      patients with Iranian ethnicity. MATERIALS AND METHODS: In a phase III trial,
      patients with previously untreated stage III and IV indolent and aggressive B
      cell NHL were randomly assigned by using a minimization method to receive six to
      eight cycles of either R-CHOP-21 (administered every 21 days) or R-CHOP-14
      (administered every 14 days with granulocyte colony-stimulating factor). RESULTS:
      A total of 143 patients were randomly enrolled in our study (66 patients in R
      CHOP-14 group and 77 patients in R-CHOP-21), between 2011 and 2014. The mean
      follow-up was 45 months at the time of treatment analysis. The 2-year and 5-year
      PFS rates for the R-CHOP-14 group were 83.6% vs 73.6% and for R-CHOP-21 group
      were 75% vs 54%. The 2-year and 5-year OS rates for R-CHOP-14 group were 98% vs
      89% and for R-CHOP-21 group were 84.4% vs 67.5%. There was a significant
      correlation for PFS and OS in the two arms. There was no significant difference
      between adverse events with the two regimens. CONCLUSIONS: In our research
      improved survival was found with CHOP-14 as compared to CHOP-21. It is possible
      that drug metabolism in different races/ethnicities may be one important factor.

PMID- 27039800
TI  - Secretion and Expression of Matrix Metalloproteinase-2 and 9 from Bone Marrow
      Mononuclear Cells in Myelodysplastic Syndrome and Acute Myeloid Leukemia.
AB  - BACKGROUND: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV
      collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9)
      are key molecules that play roles in tumor growth, invasion, tissue remodeling,
      metastasis and stem-cell regulation by digesting extracellular matrix barriers.
      MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in
      hematological malignancies, a paucity of data is available to resolve the
      function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs)
      and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia
      (AML). OBJECTIVES: The present study aimed to investigate mRNA expression and
      gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of
      MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of
      metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C;
      rs8179090) in MDS and AML. RESULTS: The study covered cases of confirmed MDS
      (n=50), AML (n=32) and healthy controls (n=110). MMP- 9 mRNA expression revealed
      2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70%
      blasts). Secretion of gelatinase- B also revealed the MMP-9 mRNA expression and
      ELISA data also supported these data. We noted that those patients having more
      blast crises presented with more secretion of MMP-9 and its mRNA expression. In
      contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS
      (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were
      1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T
      genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed
      significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS,
      while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML.
      CONCLUSIONS: In view of our results, MMP-9 revealed synergistic secretion and
      expression in blast crises of MDS and AML with 'gene' polymorphic effects and is
      significantly associated with increased risk with tobacco, cigarette and
      environmental exposure. Release and secretion of these enzymes may influence
      hematopoietic cell behavior and may be important in the clinical point of view.
      It may offer valuable tools for diagnosis and prognosis, as well as possible
      targets for the treatments.

PMID- 27039801
TI  - Clinico-Epidemiological Profile of Patients with Polycythaemia Rubra Vera - a
      Five Year Experience from a Tertiary Care Center.
AB  - BACKGROUND: Polycythaemia rubra vera (PV) is a Philadelphia chromosome negative
      myeloproliferative neoplasm characterized by increased red cell production,
      independent of the mechanisms that regulate normal erythropoiesis. The aim of
      this study was to analyze the clinico-epidemiological profile of Pakistani
      patients with PV. MATERIALS AND METHODS: In this retrospective cross sectional
      study, 26 patients with PV were enrolled from January 2010 to December 2014. They
      were diagnosed based on WHO criteria. RESULTS: The mean age was 53.4+/-9.31 years
      (range 36-72) and the male to female ratio was 2:1. Overall 30.7% of patients
      were asymptomatic. In symptomatic patients, major complaints were headache
      (30.8%), abdominal discomfort (23.1%), blurred vision (15.3%), pruritus (11.5%)
      and vascular incidents (11.5%). Physical examination revealed plethoric face and
      splenomegaly as predominant findings, detected in 34.6% and 30.7%, respectively,
      with the mean splenic span of 15.9+/-2.04cm. The mean hemoglobin was 18.1+/-1.9
      g/dl with the mean hematocrit of 55.6+/-8.3%. The mean total leukocyte count was
      12.8+/-7.1x109/l and the platelet count 511+/-341.9x109/l. Mean erythrocyte
      sedimentation rate was 3.5+/-1.22mm/hr. Serum lactate dehydrogenase, serum
      creatinine and uric acid were 552.7+/-309.2, 0.8+/-0.17 and 6.60+/-1.89
      respectively. CONCLUSIONS: PV in Pakistani patients, unlike in the West, is seen
      in a moderately young population. The disease is frequently seen in male gender
      and primarily patients present with symptoms related to hyperviscosity.

PMID- 27039802
TI  - Adult Primary Myelodysplastic Syndrome: Experience from a Tertiary Care Center in
      Pakistan.
AB  - BACKGROUND: Primary myelodysplastic syndrome (MDS) is an acquired clonal disorder
      of myeloid progenitor cells, characterized by peripheral cytopenias in the
      presence of hypercellular marrow with dysplastic features. Our aim was to study
      the demographical and clinicopathological features of adult Pakistani patients
      with MDS at disease presentation. MATERIALS AND METHODS: This single centre study
      was conducted at Liaquat National Hospital and Medical College, extending from
      January 2010 to December 2014. Data were retrieved from the patient archives.
      RESULTS: Overall 45 patients were diagnosed at our institution with de novo MDS
      during the study period. There were 28 males and 17 females. Age ranged between
      18 and 95 years with a mean age of 57.6+/-17.4 years and median of 64 years. The
      male to female ratio was 1.7:1. The main presenting complaints were generalized
      fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and weight loss
      (11.1%). Examination was unremarkable in 42.2% of patients. Physical examination
      revealed pallor in 37.7%, followed by petechial and purpuric rashes in 20%. The
      commonest laboratory finding was anemia (hemoglobin <10 g/dl in 41 (91.1%)
      patients. Out of these, 27 (60%) patients had normocytic anemia, followed by
      macrocytic (22.2%) and microcytic (8.8%). CONCLUSIONS: Primary MDS in Pakistani
      patients demonstrates a male preponderance. The proportion of anemic patients was
      high in our series with predominance of normocytic anemia. However, other clinico
      hematological features appear comparable to published data.

PMID- 27039803
TI  - BRCA1 Gene Mutation Screening for the Hereditary Breast and/or Ovarian Cancer
      Syndrome in Breast Cancer Cases: a First High Resolution DNA Melting Analysis in
      Indonesia.
AB  - Specific patterns of the hereditary breast and ovarian cancer (HBOC) syndrome are
      related to mutations in the BRCA1 gene. One hundred unrelated breast cancer
      patients were interviewed to obtain clinical symptoms and signs, pedigree and
      familial history of HBOC syndrome related cancer. Subsequently, data were
      calculated using the Breast and Ovarian Analysis of Disease Incidence and Carrier
      Estimation Algorithm (BOADICEA) risk prediction model. Patients with high score
      of BOADICEA were offered genetic testing. Eleven patients with high score of
      BOADICEA, 2 patients with low score of BOADICEA, 2 patient's family members and
      15 controls underwent BRCA1 genetic testing. Mutation screening using PCR-HRM was
      carried out in 22 exons (41 amplicons) of BRCA1 gene. Sanger sequencing was
      subjected in all samples with aberrant graph. This study identified 10 variants
      in the BRCA1 gene, consisting of 6 missense mutations (c.1480C>A, c.2612C>T,
      c.2566T>C, c.3113A>G, c.3548 A>G, c.4837 A>G), 3 synonymous mutations (c.2082 C>
      T, c.2311 T> C and c.4308T>C) and one intronic mutation (c.134+35 G>T). All
      variants tend to be polymorphisms and unclassified variants. However, no known
      pathogenic mutations were found. 

PMID- 27039804
TI  - Prognostic Factors and Survival in Acute Myeloid Leukemia Cases: a Report from
      the Northeast of Iran.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a clonal hematopoietic disorder
      resulting from genetic alterations in normal hematopoietic stem cells. The aim of
      this study was to evaluate prognostic factors and survival of AML patients in the
      Northeast of Iran. MATERIALS AND METHODS: This retrospective study covered 96
      patients with AML referred to Emam Reza Hospital, Mashhad city, Iran, from 2009
      to 2015. Age, sex, blood group, type of AML, fever, consumption of amphotericin
      B, cytogenetic forms and survival were analyzed. Also, WBC, hemoglobin and
      platelet levels were checked. Mean follow-up was 30.5 months (60.4% mortality).
      Survival was plotted by GraphPad Prism 5 with Log-rank test. RESULTS: The mean
      age for all AML patients at diagnosis was 40.4 years (range, 17-77 years). Some
      42.7% patients were aged <35 years and 40.6% were male. In all patients, 76% had
      fever and 50% consumed amphotericin. T(15;17)(q22;q21) had the most prevalence
      (37.7%) compared to other forms. Out of 92 patients, O+(30.4%) was the most
      common blood group and AML-M5 (28.3%) the most common subtype. There was a
      significant difference in survival based on WBC and consumption of amphotericin B
      (P<0.05). CONCLUSIONS: WBC level, fever and consumption of amphotericin B proved
      to be factors for survival of AML patients. The mean age for patients in Iran is
      lower than other areas in the World and also survival in this study was higher
      than in other studies.

PMID- 27039805
TI  - Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive
      Properties of U87MG Glioblastoma Cells through a Possible NF-kappaB-Mediated
      Mechanism.
AB  - Identification of novel therapeutics in glioblastoma remains crucial due to the
      devastating and infiltrative capacity of this malignancy. The current study was
      aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results
      demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells
      in a dosedependent manner and also inhibited classical NF-kappaB signaling
      pathway. ATO further upregulated expression of Bax as an important proapoptotic
      target of NF-kappaB and also inhibited mRNA expression of survivin, c-Myc and
      hTERT and suppressed telomerase activity. Moreover, ATO significantly increased
      adhesion of U87MG cells and also diminished transcription of NF-kappaB down
      stream targets involved in cell migration and invasion, including cathepsin B,
      uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B,
      MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known
      signaling in glioblastoma dissemination. Taken together, here we suggest that ATO
      inhibits survival and invasion of U87MG cells possibly through NF-kappaB-mediated
      inhibition of survivin and telomerase activity and NF-kappaB-dependent
      suppression of cathepsin B, MMP-2 and MMP-9. 

PMID- 27039806
TI  - Central, Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of
      35 Cases from Pakistan Plus a Detailed Review of the Published Literature.
AB  - BACKGROUND: Central neurocytomas are rare neuronal neoplasms with a favorable
      prognosis. They are typically located in the lateral ventricles of the brain and
      mostly histologically correspond to WHO grade II with a Mib 1 labelling index of
      <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for
      example, are called "extraventricular neurocytomas". A few tumors histologically
      show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2
      % and are designated as "atypical neurocytomas. AIM: The aim of our study was to
      describe the common as well as unusual morphologic features and the role of
      various immunohistochemical stains in the diagnosis of these rare tumors.
      MATERIALS AND METHODS: We retrieved and reviewed 35 cases diagnosed between 2001
      and 2015. RESULTS: Sixty percent of patients were males, and the mean age was 26
      years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular.
      Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All
      cases showed the classic morphology comprising nests and sheets of uniform, round
      cells with uniform round to oval nuclei with finely speckled chromatin and
      perinuclear cytoplasmic clearing (halos). All cases also showed delicate,
      fibrillary, neuropil-like matrices. Other common histologic features included
      capillary-sized blood vessels in a branching pattern in 57.1%, foci of
      calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings
      included Homer- Wright or true rosettes in 8.6% and ganglioid cells in 2.9%.
      Synaptophysin was the most consistent and valuable marker, being positive in
      almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases.
      Follow up was available in 13 patients. Of these 9 had histologically typical and
      4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due
      to complications of surgery within one month, while 12 (including 3 with atypical
      neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients
      (histologically consistent with typical morphology) almost 9 years after surgery.
      Only 4 patients, including 2 with atypical tumors, received postoperative
      radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent
      with prolonged, recurrence free survival and most patients, even without
      receiving radiation therapy, were alive and well for many years, even a decade or
      more after surgery, without developing any recurrence, indicating the benign
      nature of these neoplasms.

PMID- 27039807
TI  - Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents
      Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for
      Cancers.
AB  - Alteration of the acetylation status of chromatin and other non-histone proteins
      by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment
      of cancers. The present study was sought to identify compounds with positive
      pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by
      Cai et al, 2015 formed the test compounds for the present pharmacological
      evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in
      comparison to all the compounds in the analogue dataset owing to its better
      electrostatic interactions and hydrogen bonding patterns. In order to identify
      compounds with even better high affinity and pharmacological profile than 6H and
      Vorinostat, virtual screening was performed. A total of 83 compounds similar to
      Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695
      (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and
      6H, were the best docked compounds among the virtually screened compounds.
      However, in spite of having good affinity, none of the virtually screened
      compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was
      predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our
      extensive analysis involving binding affinity analysis, ADMET properties
      predictions and pharmacophoric mappings, we report Vorinostat hydroxamate
      analogue 6H to be a potential candidate for HDAC inhibition in treatment of
      cancers through an epigenetic strategy. 

PMID- 27039808
TI  - Estimating the Burden of Cancers Attributable to Smoking Using Disability
      Adjusted Life Years in Indonesia.
AB  - Tobacco use is a well-established risk factor for many types of cancers. Recent
      data on selected cancer incidence and mortality related to smoking in the
      Indonesian population are provided in this study. Morbidity and mortality data
      were derived from GLOBOCAN 2012 and the population attributable fraction (PAF)
      was estimated using the standard methodology developed by the World Health
      Organization. Using these data, we calculated disability adjusted life year
      (DALY) values for smoking-related cancer. The DALY was estimated by summation of
      the years lived with disability (YLD) and years life lost due to premature death
      (YLL). The cancer cases related to smoking in Indonesia numbered 45,132,
      accounting for 35,580 cancer deaths. The morbidity and mortality of lung cancer
      can be considered as the highest priority in both men and women. Furthermore the
      greatest YLD due to smoking in Indonesian men and women were from pancreas and
      lung cancers. For YLL among men, the highest years lost were from lung and liver
      cancers. On the other hand, among women lung oral cavity and lip were most
      important. Based on the DALY indicator, burden priorities for Indonesian men were
      lung cancer (298,980), liver cancer (60,367), and nasopharynx (46,185), while
      among Indonesian women they were lung cancer (34,119), cervix uteri (9,213) and
      pancreas cancer (5,433). In total, Indonesian burden of cancers attributed to
      smoking was 638,682 DALY. This study provides evidence about the burden of
      cancers caused by smoking as a rational basis for initiating national tobacco
      control policies in Indonesia. 

PMID- 27039809
TI  - The ICAM-1 Gly241Arg Polymorphism is Not Associated With Polycystic Ovary
      Syndrome - Results from a Case Control study in Kashmir, India.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is considered to be a multifactorial
      disorder resulting from the interaction of several predisposing and protective
      genetic variants. PCOS is associated with low-grade chronic inflammation.
      Elevated levels of inflammatory markers including intercellular adhesion molecule
      1 (ICAM-1) are demonstrated in women with PCOS. Recent evidence indicates a
      significant linkage between a locus on chromosome 19p13 and multifactorial
      diseases that have an inflammatory component. The aim of the study was to assess
      the possible association of Gly241Arg polymorphism of ICAM-1 gene located on
      chromosome 19p13 in determining risk of PCOS in Kashmiri women. MATERIALS AND
      METHODS: Gly241Arg SNP in DNA from peripheral blood leukocytes of 220 PCOS cases
      and 220 age matched non-PCOS healthy controls was analysed using allel specific
      PCR. RESULTS: The genotype and allele frequency distributions of Gly241Arg SNP
      showed insignificant difference between the PCOS cases and control women,
      indicating no role of this SNP in PCOS susceptibility. The odds ratio for Arg/Arg
      genotype was 0.87 (95% CI=0.32-2.3) [P=0.79], for Gly/Arg genotype was 0.98 (95%
      CI= 0.66-1.47) [P=1] and for Arg/Arg+Gly/Arg genotype was 0.97 (95% CI=0.65-1.45)
      [P=0.92]. The genotypic frequencies of ICAM-1codon 241 showed statistically
      insignificant difference between cases and controls (chi2=0.07; p=0.96) Nor the
      studied polymorphism was found to affect clinical and laboratory parameters
      significantly. CONCLUSIONS: Although Gly241Arg polymorphism have not shown
      significant association with PCOS. Further, specifically designed studies on
      large cohorts are required to conclusively establish any role of ICAM-1 gene
      polymorphisms in PCOS in our study.

PMID- 27039810
TI  - Prevalence and Factors Associated with Opisthorchis viverrini Infection in
      Khammouane Province, Lao PDR.
AB  - Opisthorchis viverrini (OV) liver flukes are common parasites found in central
      and southern Laos and constitute a major public health problem in the country.
      Laos people continue to have the habit of extensively consuming raw or half
      cooked fish which are intermediate hosts. This study aimed to study the
      prevalence and factors associated with OV infection in the population of Thakek
      district, Khammouane Province. This cross-sectional analytic study covered 237
      subjects who filled out structured questionnaires. Fecal examination for OV
      infection was performed by Kato's thick smear method. Data analysis was carried
      out using STATA Version 10.0. Multiple logistic regression was applied. The
      results showed that the infection rate of OV was 54.8 %. Factors associated with
      OV infections were gender, a habit of defecation in fields and raw fish (goi
      bplaa dip) consumption. Opisthorchiasis and associated cholangiocarcinoma
      development thus appear to remain as important concerns in Laos. 

PMID- 27039811
TI  - Leukemic Oral Manifestations and their Management.
AB  - Leukemia is the most common neoplastic disease of the white blood cells which is
      important as a pediatric malignancy. Oral manifestations occur frequently in
      leukemic patients and may present as initial evidence of the disease or its
      relapse. The symptoms include gingival enlargement and bleeding, oral ulceration,
      petechia, mucosal pallor, noma, trismus and oral infections. Oral lesions arise
      in both acute and chronic forms of all types of leukemia. These oral
      manifestations either may be the result of direct infiltration of leukemic cells
      (primary) or secondary to underlying thrombocytopenia, neutropenia, or impaired
      granulocyte function. Despite the fact that leukemia has long been known to be
      associated with oral lesions, the available literature on this topic consists
      mostly of case reports, without data summarizing the main oral changes for each
      type of leukemia. Therefore, the present review aimed at describing oral
      manifestations of all leukemia types and their dental management. This might be
      useful in early diagnosis, improving patient outcomes. 

PMID- 27039812
TI  - Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote
      Gastric Cancer.
AB  - However, the incidence of gastric cancer (GC) has been decreased in past decades;
      GC is the second cause of cancer related death in the world. Evidence has
      illustrated that several factors including Helicobacter pylori (H. pylori)
      infection, host genetics, and environmental factors (smoking and particularly
      diet) may play a crucial role in gastric carcinogenesis. It has been demonstrated
      that high consumption of fresh fruits, vegetables, high level of selenium and
      zinc in drinking water, sufficient iron, and cholesterol protect against GC,
      while; smoked , pickled, and preserved foods in salt, and nitrites increase the
      risk of GC. Epidemiological studies have also proved that H. pylori infection and
      a high salt diet could independently induce atrophic gastritis and intestinal
      metaplasia. Recently, studies have been demonstrated that dietary factors
      directly influence H. pylori virulence. The use of appropriate diet could reduce
      levels of H. pylori colonization or virulence and prevent or delay development of
      peptic ulcers or gastric carcinoma. This is attractive from a number of
      perspectives including those of cost, treatment tolerability, and cultural
      acceptability. This review will describe new insights into the pathogenesis of H.
      pylori in relation to environmental factors, especially dietary, not only to find
      the developed means for preventing and treating GC, but also for understanding
      the role of chronic inflammation in the development of other malignancies. 

PMID- 27039813
TI  - Coexisting JAK2V617F and CALR Exon 9 Mutations in Myeloproliferative Neoplasms -
      Do They Designate a New Subtype?
AB  - The classic BCR-ABL1-negative myeloproliferative neoplasm is an operational sub
      category of MPNs that includes polycythemia vera (PV), essential thrombocythemia
      (ET), and primary myelofibrosis (PMF). The JAK2V617F mutation is found in ~ 95%
      of PV and 50-60% of ET or PMF. In most of the remaining JAK2V617F- negative PV
      cases, JAK2 exon 12 mutations are present. Amongst the JAK2V617F-negative ET or
      PMF 5-10% of patients carry mutations in the MPL gene. Prior to 2013, there was
      no specific molecular marker described in the remaining 30-40% ET and PMF. In
      December 2013, two research groups independently reported mutations in the gene
      CALR found specifically in ET (67-71%) and PMF (56-88%) but not in PV. Initially
      CALR mutations were reported mutually exclusive with JAK2 or MPL. However, co
      occurrence of CALR mutations with JAK2V617F has been reported recently in a few
      MPN cases. Many studies have reported important diagnostic and prognostic
      significance of CALR mutations in ET and PMF patients and CALR mutation screening
      has been proposed to be incorporated into WHO diagnostic criteria for MPN. It is
      suggestive in diagnostic workup of MPN that CALR mutations should not be studied
      in MPN patients who carry JAK2 or MPL mutations. However JAK2V617F and CALR
      positive patients might have a different phenotype and clinical course, distinct
      from the JAK2-positive or CALR-positive subgroups and identification of the true
      frequency of these patients may be an important factor for defining the
      prognosis, risk factors and outcomes for MPN patients. 

PMID- 27039814
TI  - Recombinant Human Bone Morphogenetic Protein-2 in Development and Progression of
      Oral Squamous Cell Carcinoma.
AB  - Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor
      beta superfamily, regulate many cellular activities including cell migration,
      differentiation, adhesion, proliferation and apoptosis. Use of recombinant human
      bone morphogenic protein?2 (rhBMP?2) in oral and maxillofacial surgery has seen a
      tremendous increase. Due to its role in many cellular pathways, the influence of
      this protein on carcinogenesis in different organs has been intensively studied
      over the past decade. BMPs also have been detected to have a role in the
      development and progression of many tumors, particularly disease-specific bone
      metastasis. In oral squamous cell carcinoma - the tumor type accounting for more
      than 90% of head and neck malignancies- aberrations of both BMP expression and
      associated signaling pathways have a certain relation with the development and
      progression of the disease by regulating a range of biological functions in the
      altered cells. In the current review, we discuss the influence of BMPs 
      especially rhBMP-2- in the development and progression of oral squamous cell
      carcinoma. 

PMID- 27039815
TI  - Online Social Networks - Opportunities for Empowering Cancer Patients.
AB  - Online social network technologies have become important to health and apply in
      most health care areas. Particularly in cancer care, because it is a disease
      which involves many social aspects, online social networks can be very useful.
      Use of online social networks provides a suitable platform for cancer patients
      and families to present and share information about their medical conditions,
      address their educational needs, support decision making, and help to coping with
      their disease and improve their own outcomes. Like any other new technologies,
      online social networks, along with many benefits, have some negative effects such
      as violation of privacy and publication of incorrect information. However, if
      these effects are managed properly, they can empower patients to manage cancer
      through changing behavioral patterns and enhancing the quality of cancer patients
      lives This paper explains some application of online social networks in the
      cancer patient care process. It also covers advantages and disadvantages of
      related technologies. 

PMID- 27039816
TI  - Stereotactic Body Radiation Therapy for Treatment of Spinal Bone Metastasis.
AB  - Stereotactic body radiation therapy (SBRT) appears an effective and safe
      treatment modality for spinal bone metastasis, which can enhance local control
      and improve quality of life. Life expectation, predicted fracture risk,
      localization, quality, size and number of metastasis and presence or absence of
      nerve compression seem to be important factors in decision-making for treatment.
      Further studies are needed to identify subsets of patient which will most benefit
      from treatment. 

PMID- 27039817
TI  - Increased Free Circulating DNA Integrity Index as a Serum Biomarker in Patients
      with Colorectal Carcinoma.
AB  - BACKGROUND: Cell-free DNA circulating in blood is a candidate biomarker for
      malignant tumors. Unlike uniformly truncated DNA released from apoptotic non
      diseased cells, DNA released from necrotic cancer cells varies in size.
      OBJECTIVES: To measure the DNA integrity index in serum and the absolute DNA
      concentration to assess their clinical utility as potential serum biomarkers for
      colorectal carcinoma (CRC) compared to CEA and CA19-9. MATERIALS AND METHODS:
      Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age
      matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR)
      using two sets of primers (115 and 247 bp) amplifying different lengths of DNA
      fragments. The DNA integrity index was calculated as the ratio of q-PCR results
      of ALU 247/ ALU 115bp. RESULTS: Serum DNA integrity was statistically
      significantly higher in CRC patients compared to the benign and control groups
      (p<0.001). ROC curves for differentiating CRC patients from normal controls and
      benign groups had areas under curves of 0.90 and 0.85 respectively. CONCLUSIONS:
      The DNA integrity index is superior to the absolute DNA concentration as a
      potential serum biomarker for screening and diagnosis of CRC. It may also serve
      as an indicator for monitoring the progression of CRC patients. Combining CEA and
      CA19-9 with either of the genetic markers studied is better than either of them
      alone.

PMID- 27039818
TI  - Knowledge, Attitudes and Behavior of Bangkok Metropolitan Women Regarding
      Cervical Cancer Screening.
AB  - PURPOSE: To assess knowledge, attitudes and cervical cancer screening behavior of
      Bangkok Metropolitan women. MATERIALS AND METHODS: Thai women, aged 25-to-65
      years old, having lived in Bangkok for 5 years or more were invited to
      participate in the study. After signing informed consent, all women were asked to
      complete a self-questionnaire (Thai language) with literate assistance if needed.
      The questionnaire was divided into 3 parts: (I) demographic data; (II) knowledge
      about cervical cancer screening; and (III) behavior and attitudes, towards
      cervical cancer screening. Adequate screening was defined as women who had >=two
      cervical cancer screening tests except women aged 25-30 years who may have only
      one screening, and the last screen was within 5 year or had had regular
      screening. RESULTS: Of 4,339 women, there were 1,857 (42.8%) with adequate
      screening and 2,482 (57.2%) with inadequate screening. Significant factors
      associated with inadequate screening included age < 45 years, pre-menopausal
      status, family monthly income <625 USD, no reported sexual intercourse,
      nulliparous, no knowledge, lack of awareness and poor attitudes. Three major
      reasons provided by women for inadequate screening were no symptoms (54.4%), fear
      of pain (33.2%), and embarrassment (34.6%). CONCLUSIONS: Personal features,
      knowledge, and attitudes influence screening behavior of Bangkok Metropolitan
      women. The three most common reasons of women for not undergoinging screening are
      no symptoms, fear of pain, and embarrassment. These factors should be the focus
      of attention to improve coverage of cervical cancer screening in Bangkok.

PMID- 27039819
TI  - Lack of Associations between TNF-alphaPolymorphisms and Cervical Cancer in Thai
      women.
AB  - The risk of developing cervical cancer in women infected with human
      papillomavirus (HPV) may be influenced by an individual's genetic susceptibility.
      Published data linking single nucleotide polymorphisms (SNPs) in the tumor
      necrosis factor-alpha (TNF-?) promoter region at positions -308G>A (rs1800629)
      and -238G>A (rs361525) to cervical cancer risk have been inconclusive. In this
      study, we examined 251 cervical specimens and classified them into two groups
      according to their cytological findings: 121 cancer cases and 130 controls (low
      grade squamous intraepithelial lesion and normal cytology). All specimens were
      typed by PCR and sequencing for TNF-alphapromoter -308G>A (rs1800629) and -238G>A
      (rs361525). The genotype distribution of SNPs in either rs1800629 or rs361525 did
      not significantly demonstrate higher frequency in the cancer group (p=0.621 and
      p=0.68, respectively). Based on these results, neither the TNF-alphapromoter 
      308G>A (rs1800629) nor the -238G>A (rs361525) polymorphism presents a major risk
      factor for cervical cancer among Thai women. Larger studies are necessary to
      elucidate possible genetic mechanisms influencing cervical cancer development. 

PMID- 27039820
TI  - Effects of 5-Aza-2'-Deoxycytidine, Bromodeoxyuridine, Interferons and Hydrogen
      Peroxide on Cellular Senescence in Cholangiocarcinoma Cells.
AB  - Cellular senescence, a barrier to tumorigenesis, controls aberrant proliferation
      of cells. We here aimed to investigate cellular senescence in immortalized
      cholangiocyte and cholangiocarcinoma cell lines using five different inducing
      agents: 5-aza-2'deoxycytidine, bromodeoxyuridine, interferons (IFNbeta and
      IFNgamma), and hydrogen peroxide. We analyzed senescence characteristics, colony
      formation ability, expression of genes involved in cell cycling and interferon
      signaling pathways, and protein levels. Treatment with all five agents decreased
      cell proliferation and induced cellular senescence in immortalized cholangiocyte
      and cholangiocarcinoma cell lines with different degrees of growth-inhibitory
      effects depending on cell type and origin. Bromodeoxyuridine gave the strongest
      stimulus to inhibit growth and induce senescence in most cell lines tested.
      Expression of p21 and interferon related genes was upregulated in most
      conditions. The fact that bromodeoxyuridine had the strongest effects on growth
      inhibition and senescence induction implies that senescence in cholangiocarcinoma
      cells is likely controlled by DNA damage response pathways relating to the
      p53/p21 signaling. In addition, interferon signaling pathways may partly regulate
      this mechanism in cholangiocarcinoma cells. 

PMID- 27039821
TI  - Prevalence and Clinical Profile of EGFR Mutation In Non- Small-Cell Lung
      Carcinoma Patients in Southwest China.
AB  - AIMS: To investigate the distribution of epidermal growth factor receptor (EGFR)
      mutations, and explore any relationships with clinical characteristics in non
      small-cell lung carcinoma (NSCLC) patients. MATERIALS AND METHODS: EGFR mutations
      were assessed by ADx-ARMS in 261 NSCLC patients from West China Hospital of
      Sichuan University. Relationships between EGFR mutation and clinical
      characteristics were analyzed by SPSS. RESULTS: The EGFR mutation rate was 48.7%
      (127/261), 19-del and L858R mutations occurred predominantly, accounting for
      33.1% and 40.9%, respectively, in mutated cases. Moreover, 10.2% patients were
      found to carry double mutations. EGFR mutations occurred more frequently in women
      (57.5%) than in men (41.8%) (P=0.01), and were more frequent in non-smokers
      (61.2%) than in former or current smokers (31.2%) (P<0.00). In addition, they
      were more common in adenocarcinomas (52.8%) and adenosquamous carcinomas (42.8%)
      than in squamous cell carcinomas (14.8%) (p<0.00). However, only smoking history
      and pathological types, rather than gender, proved to be associated with EGFR
      mutations on multivariate logistic regression analysis. No significant
      differences in pathological stage and metastasis status were found between EGFR
      wild-type and mutated cases, although EGFR mutation type was related to
      pathological type (p=0.00) - 19-del, L858R and other mutation types respectively
      occurred in 34.2%, 42.5% and 23.3% of adenocarcinomas, but in 14.3%, 0% and 85.7%
      of non-adenocarcinomas. CONCLUSIONS: The EGFR mutation rate was 48.7% in NSCLCs
      in Southwest China, so that nearly 40% patients might benefit from targeted
      therapies. Smoking status and pathological types were independent predictors of
      EGFR mutation, while EGFR mutation type was related to only pathological type,
      rather than smoking status.

PMID- 27039822
TI  - Safety and Management of Toxicity Related to Aflibercept in Combination with
      Fluorouracil, Leucovorin and Irinotecan in Malaysian Patients with Metastatic
      Colorectal Cancer.
AB  - BACKGROUND: Between October 2012 and February 2015, 25 patients with metastatic
      colorectal cancer (mCRC) (mean age, 57.0 +/- 12.1 years) were granted access to
      aflibercept via the Aflibercept Named Patient Program at four centers. MATERIALS
      AND METHODS: Here we reported the initial experience of aflibercept / FOLFIRI in
      combination. We evaluated treatment-related adverse events (AEs), progression
      free survival (PFS) and overall survival (OS). RESULTS: The majority of the
      patients experienced gastrointestinal toxicity (grade 1-2), with diarrhea (52%),
      mucositis (52%), and nausea/vomiting (20%) being largely observed. Neutropenia
      (16%) and febrile neutropenia (8%) were common grade 3-4 hematological events.
      Aflibercept-related toxicity was managed as per practice guidelines. No grade 5
      event was reported. Median PFS was 6.12 months (95% CI, 4.80-7.20) and OS was 12
      months (95% CI, 9.80-14.18). The partial response (PR), stable disease (SD), and
      progressive disease (PD) rates were 25% (95% CI: 23.4-27.0), 37.5% (95% CI: 31.6
      43.3), and 37.5% (95% CI: 22.5-52.5), respectively. CONCLUSIONS:
      Aflibercept/FOLFIRI can be administered safely in a second line setting to
      Malaysian patients with mCRC, as the AEs experienced were generally reversible
      and manageable. The safety and efficacy outcomes were consistent with those
      observed in Western populations.

PMID- 27039823
TI  - Rare Helicobacter pylori Infection May Explain Low Stomach Cancer Incidence:
      Ecological Observations in Bali, Indonesia.
AB  - The incidence rate of stomach cancer in Bali, Indonesia, is estimated to be
      strikingly lower than that in Japan. We conducted an on-site ecological study to
      investigate the association between the stomach cancer incidence and Helicobacter
      pylori (H. pylori) infection. Recruiting 291 healthy persons (136 men and 155
      women) from the general population in Bali, Indonesia, we conducted a urea breath
      test (UBT) to examine H. pylori infection, along with a pepsinogen test to detect
      chronic atrophic gastritis and urine analysis to estimate sodium and potassium
      excretion. UBT positivities were 9% (2-15, 95% confidence interval) for men and
      7% (1-12) for women, and positive cases for H. pylori IgG antibodies were 1% (0
      3) for men and 3% (0-5) for women, significantly lower than the respective values
      in Japan. Positive pepsinogen tests in Bali were 0% (0-0) for men and 1% (0-4)
      for women, also significantly lower than the Japanese figures. Computed values
      for daily salt excretion were 13.3+/-4.1 g (mean +/- SD) for men and 11.1+/-3.1 g
      for women, as high as corresponding Japanese consumption values. Moreover, the
      estimated potassium excretion was 3.2+/-0.7 g for men and 2.8+/-0.6 g for women
      in Bali, significantly higher than the figures in Japan. There were no
      associations across genetic polymorphisms of IL-beta, TNF-alpha, and PTPN11 with
      UBT positivity. The low incidence of stomach cancer in Bali may thus mainly be
      due to the rare H. pylori infection. Namely, the bacterium infection seems to be
      a critical factor for gastric cancer rather than host or other environmental
      factors. 

PMID- 27039824
TI  - Impact of Adaptive Radiotherapy on Locally Advanced Head and Neck Cancer - A
      Dosimetric and Volumetric Study.
AB  - Objective of the study is to evaluate volumetric and dosimetric alterations
      taking place during radiotherapy for locally advanced head and neck cancer
      (LAHNC) and to assess benefit of replanning in them. MATERIALS AND METHODS:
      Thirty patients with LAHNC fulfilling the inclusion and exclusion criteria were
      enrolled in a prospective study. Planning scans were acquired both pre-treatment
      and after 20 fractions (mid-course) of radiotherapy. Single plan (OPLAN) based on
      initial CT scan was generated and executed for entire treatment course. Beam
      configuration of OPLAN was applied to anatomy of interim scan and a hybrid plan
      (HPLAN30) was generated. Adaptive replanning (RPLAN30) for remaining fractions
      was done and dose distribution with and without replanning compared for remaining
      fractions. RESULTS: Substantial shrinkage of target volume (TV) and parotids
      after 4 weeks of radiotherapy was reported (p<0.05). No significant difference
      between planned and delivered doses was seen for remaining fractions. Hybrid
      plans showed increase in delivered dose to spinal cord and parotids for remaining
      fractions. Interim replanning improved homogeneity of treatment plan and
      significantly reduced doses to cord (Dmax, D2% and D1%) and ipsilateral parotid
      (D33%, D50% and D66%) (p<0.05). CONCLUSIONS: Use of one or two mid-treatment CT
      scans and replanning provides greater normal tissue sparing alongwith improved TV
      coverage.

PMID- 27039825
TI  - Effects of Epothilone A in Combination with the Antidiabetic Drugs Metformin and
      Sitagliptin in HepG2 Human Hepatocellular Cancer Cells: Role of Transcriptional
      Factors NF-kappaB and p53.
AB  - Type 2 diabetes mellitus patients are at increased risk of many forms of
      malignancies, especially of the pancreas, colon and hepatocellular cancer.
      Unfortunately, little is known of the possible interaction between antidiabetic
      drugs and anticancer agents. The present study investigates the influence of
      metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the
      microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular
      liver carcinoma cell line (HepG2) viability and apoptosis were determined by the
      MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D,
      respectively, after treatment with EpoA, metformin or sitagliptin. The levels of
      nuclear factor NF-kappaB and p53 were evaluated in the presence and absence of
      inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not.
      EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the
      level of NF-kappaB. Only MET enhanced the proapoptotic effect of EpoA. The
      EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led
      to apoptosis independent of p53, decreasing the level of NF-kappaB. These
      findings support the link between NF-kappaB and p53 in the modulation of
      apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the
      combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic
      effect on liver cancer cells than each of the compounds alone. The therapeutic
      advantages of the combination of EpoA with MET may be valuable in the treatment
      of patients with diabetes mellitus type 2 (T2DM) and liver cancer. 

PMID- 27039826
TI  - The Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Report on
      Baseline Characteristics of Participants.
AB  - OBJECTIVE: To describe baseline headache characteristics of children and
      adolescents participating in a multicenter, randomized, double-blinded, placebo
      controlled, comparative effectiveness study of amitriptyline, topiramate, and
      placebo for the prevention of migraine (CHAMP Study). METHODS: Children and
      adolescents (age 8-17 years old, inclusive) diagnosed with migraine with or
      without aura, having headaches at least four times per month were enrolled from
      2012 through 2014. The trial involved a baseline period (minimum of 28 days)
      during which prospective diaries were completed and demographics and headache
      features obtained. RESULTS: A total of 488 children and adolescents (mean age
      14.0 +/- 2.4 years) agreed to participate in the trial, with 361 randomized and
      127 not randomized. Randomized subjects had a 5.5 +/- 3.1 year history of
      headaches, with 15.1 +/- 7.1 headache days per month (based upon retrospective
      report at screening visit). Prospective diaries reported 11.5 +/- 6.1 headache
      days per 28 day baseline. Across this 28 day period, reported headache days per
      week were stable (about 3 headache days per week). Recording of individual
      headache features by diary (n = 4136 headache days) showed characteristics
      consistent with migraine (mean duration 10.5 +/- 8.1 hours, mean severity 6.0 +/-
      2.1, 60% throbbing, 55% with activity worsening headaches, 55% with photophobia,
      and 47% with phonophobia). CONCLUSIONS: Baseline data from the CHAMP Study
      suggested that the randomized sample was representative of the real world
      population of children and adolescents that present for treatment of migraine.
      Headaches in children and adolescents recorded during a 28 day prospective
      baseline period in this multi-site comparative effectiveness study did not change
      over the course of the baseline period, even though a clear diagnosis,
      recommendation for effective acute treatment, and standardized education about
      healthy habits occurred prior to the diary collection period.

PMID- 27039828
TI  - Update on the nomenclature of human neutrophil antigens and alleles.

PMID- 27039829
TI  - The structure-function relationship for alumina supported platinum during the
      formation of ammonia from nitrogen oxide and hydrogen in the presence of oxygen.
AB  - We study the structure-function relationship of alumina supported platinum during
      the formation of ammonia from nitrogen oxide and dihydrogen by employing in situ
      X-ray absorption and Fourier transform infrared spectroscopy. Particular focus
      has been directed towards the effect of oxygen on the reaction as a model system
      for emerging technologies for passive selective catalytic reduction of nitrogen
      oxides. The suppressed formation of ammonia observed as the feed becomes net
      oxidizing is accompanied by a considerable increase in the oxidation state of
      platinum as well as the formation of surface nitrates and the loss of NH
      containing surface species. In the presence of (excess) oxygen, the ammonia
      formation is proposed to be limited by weak interaction between nitrogen oxide
      and the oxidized platinum surface. This leads to a slow dissociation rate of
      nitrogen oxide and thus low abundance of the atomic nitrogen surface species that
      can react with the adsorbed hydrogen species. In this case the consumption of
      hydrogen through the competing water formation reaction and
      decomposition/oxidation of ammonia are of less importance for the net ammonia
      formation. 

PMID- 27039830
TI  - Quantitative Analysis of Salidroside and p-Tyrosol in the Traditional Tibetan
      Medicine Rhodiola crenulata by Fourier Transform Near-Infrared Spectroscopy.
AB  - A nondestructive, efficient, and rapid method for quantitative analysis of two
      bioactive components (salidroside and p-tyrosol) in Rhodiola crenulata, a
      traditional Tibetan medicine, by Fourier transform near-infrared (FT-NIR)
      spectroscopy was developed. Near-infrared diffuse reflectance spectra in the
      range of 4000 to 10000 cm(-1) of 50 samples of Rhodiola crenulata with different
      sources were measured. To get a satisfying result, partial least squares
      regression (PLSR) was used to establish NIR models for salidroside and p-tyrosol
      content determination. Different preprocessing methods, including smoothing,
      taking a second derivative, standard normal variate (SNV) transformation, and
      multiplicative scatter correction (MSC), were investigated to improve the model
      accuracy of PLSR. The performance of the two final models (salidroside model and
      p-tyrosol model) was evaluated by factors such as the values of correlation
      coefficient (R(2)), root mean square error of prediction (RMSEP), and root mean
      square error of calibration (RMSEC). The optimal results of the PLSR model of
      salidroside showed that R(2), RMSEP and RMSEC were 0.99572, 0.0294 and 0.0309,
      respectively. Meanwhile, in the optimization model of p-tyrosol, the R(2), RMSEP
      and RMSEC were 0.99714, 0.0154 and 0.0168, respectively. These results
      demonstrate that FT-NIR spectroscopy not only provides a precise, rapid method
      for quantitative analysis of major effective constituents in Rhodiola crenulata,
      but can also be applied to the quality control of Rhodiola crenulata.

PMID- 27039827
TI  - mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and
      differentiation.
AB  - Precise coordination of cell growth, proliferation and differentiation is
      essential for the development of multicellular organisms. Here, we report that
      although the mechanistic target of rapamycin complex 1 (mTORC1) activity is
      required for chondrocyte growth and proliferation, its inactivation is essential
      for chondrocyte differentiation. Hyperactivation of mTORC1 via TSC1 gene deletion
      in chondrocytes causes uncoupling of the normal proliferation and differentiation
      programme within the growth plate, resulting in uncontrolled cell proliferation,
      and blockage of differentiation and chondrodysplasia in mice. Rapamycin promotes
      chondrocyte differentiation and restores these defects in mutant mice.
      Mechanistically, mTORC1 downstream kinase S6K1 interacts with and phosphorylates
      Gli2, and releases Gli2 from SuFu binding, resulting in nuclear translocation of
      Gli2 and transcription of parathyroid hormone-related peptide (PTHrP), a key
      regulator of bone development. Our findings demonstrate that dynamically
      controlled mTORC1 activity is crucial to coordinate chondrocyte proliferation and
      differentiation partially through regulating Gli2/PTHrP during endochondral bone
      development. 

PMID- 27039831
TI  - Preparation and Evaluation of Solid Dispersion Tablets by a Simple and
      Manufacturable Wet Granulation Method Using Porous Calcium Silicate.
AB  - The aim of this study was to prepare and evaluate solid dispersion tablets
      containing a poorly water-soluble drug using porous calcium silicate (PCS) by a
      wet granulation method. Nifedipine (NIF) was used as the model poorly water
      soluble drug. Solid dispersion tablets were prepared with the wet granulation
      method using ethanol and water by a high-speed mixer granulator. The binder and
      disintegrant were selected from 7 and 4 candidates, respectively. The dissolution
      test was conducted using the JP 16 paddle method. The oral absorption of NIF was
      studied in fasted rats. Xylitol and crospovidone were selected as the binder and
      disintegrant, respectively. The dissolution rates of NIF from solid dispersion
      formulations were markedly enhanced compared with NIF powder and physical
      mixtures. Powder X-ray diffraction (PXRD) confirmed the reduced crystallinity of
      NIF in the solid dispersion formulations. Fourier transform infrared (FT-IR)
      showed the physical interaction between NIF and PCS in the solid dispersion
      formulations. NIF is present in an amorphous state in granules prepared by the
      wet granulation method using water. The area under the plasma concentration-time
      curve (AUC) and peak concentration (C(max)) values of NIF after dosing rats with
      the solid dispersion granules were significantly greater than those after dosing
      with NIF powder. The solid dispersion formulations of NIF prepared with PCS using
      the wet granulation method exhibited accelerated dissolution rates and superior
      oral bioavailability. This method is very simple, and may be applicable to the
      development of other poorly water-soluble drugs.

PMID- 27039832
TI  - Shifting the Linear Range in Electrospray Ionization by In-Source Collision
      Induced Dissociation.
AB  - The goal of this study was to demonstrate the utility of in-source collision
      induced dissociation for shifting the linear range in liquid chromatography
      electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). The linear
      ranges for uracil, deoxyuridine, and uridine were shifted from 0.3-300, 1-100,
      and 10-1000 ng/mL to 10-1000, 30-3000, and 100-10000 ng/mL, respectively, by
      changing the declustering potential controlling in-source collision-induced
      dissociation. This technique should be considered for control of linear range in
      simultaneous quantitative measurements of extremely different amounts of
      compounds, drugs, and metabolites using LC/ESI-MS/MS. 

PMID- 27039833
TI  - Effects of Hepatoprotective Compounds from the Leaves of Lumnitzera racemosa on
      Acetaminophen-Induced Liver Damage in Vitro.
AB  - Phytochemical investigation of the n-BuOH fraction of the mangrove plant
      Lumnitzera racemosa WILLD. (Combretaceae) led to the isolation of one new
      flavonoid glycoside; myrcetin 3-O-methyl glucuronate (1), one new phenolic
      glycoside; lumniracemoside (2) and one new aliphatic alcohol glycoside; n-hexanol
      1-O-rutinoside (3), in addition to seven known compounds (4-10). The structures
      of these compounds were determined by spectroscopic analyses (UV, IR, high
      resolution-electrospray ionization (HR-ESI)-MS, one- and two-dimensional (1D- and
      2D)-NMR). Compound 7 showed the highest hepatoprotective activity against
      acetaminophen-induced hepatotoxicity using human HepG2 cells at protection %
      value of 34.2+/-3.1%, while compounds 1, 2, 3, 6, and 9 showed weak to moderate
      hepatoprotective activity (11.6-18.9%). Almost all of these compounds showed
      stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity
      compared with the standard Trolox. These results suggest the usefulness of this
      plant extract and the isolated compounds as promising hepatoprotective agents. 

PMID- 27039834
TI  - Synthetic Studies on a Pachastrissamine Sulfur Analogue: Synthesis of a 4-epi
      Sulfur Analogue.
AB  - A versatile synthetic procedure for a sulfur analogue of pachastrissamine
      (jaspine B), which involves the tandem thiolation-cyclization of a 1,4-ditosylate
      to construct a tetrahydrothiophene ring, was developed. Nucleophilic amino
      substitution of a tetrahydrothiophene-4-sulfonate with unexpected retention of
      the configuration afforded the sulfur analogue of 4-epi-pachastrissamine. 

PMID- 27039835
TI  - Markovnikov-Selective Addition of Fluorous Solvents to Unactivated Olefins Using
      a Co Catalyst.
AB  - We developed an addition reaction of fluorous solvents to olefins using salen
      cobalt (Co) complex, N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, and
      1,1,3,3-tetramethyldisiloxane. This reaction condition was found to activate
      olefins, which enabled them to be attacked by 2,2,2-trifluoroethanol (TFE) and
      1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), both of which are electronically weak
      nucleophiles. 

PMID- 27039836
TI  - Facile Preparation of Peptides with C-Terminal N-Alkylamide via Radical-Initiated
      Dethiocarboxylation.
AB  - A new synthetic method has been developed to prepare peptides bearing a C
      terminal N-alkylamide from peptide thioacids via a radical-initiated
      dethiocarboxylation process. This method enables the introduction of various
      alkyl groups to C-terminal amides simply by replacing the amino acid building
      block. Its application to the preparation of anti-cancer drug ABT-510 is also
      reported. 

PMID- 27039837
TI  - Errata for Chemical and Pharmaceutical Bulletin.

PMID- 27039838
TI  - The rational search for selective anticancer derivatives of the peptide Trichogin
      GA IV: a multi-technique biophysical approach.
AB  - Peptaibols are peculiar peptides produced by fungi as weapons against other
      microorganisms. Previous studies showed that peptaibols are promising peptide
      based drugs because they act against cell membranes rather than a specific
      target, thus lowering the possibility of the onset of multi-drug resistance, and
      they possess non-coded alpha-amino acid residues that confer proteolytic
      resistance. Trichogin GA IV (TG) is a short peptaibol displaying antimicrobial
      and cytotoxic activity. In the present work, we studied thirteen TG analogues,
      adopting a multidisciplinary approach. We showed that the cytotoxicity is
      tuneable by single amino-acids substitutions. Many analogues maintain the same
      level of non-selective cytotoxicity of TG and three analogues are completely non
      toxic. Two promising lead compounds, characterized by the introduction of a
      positively charged unnatural amino-acid in the hydrophobic face of the helix,
      selectively kill T67 cancer cells without affecting healthy cells. To explain the
      determinants of the cytotoxicity, we investigated the structural parameters of
      the peptides, their cell-binding properties, cell localization, and dynamics in
      the membrane, as well as the cell membrane composition. We show that, while
      cytotoxicity is governed by the fine balance between the amphipathicity and
      hydrophobicity, the selectivity depends also on the expression of negatively
      charged phospholipids on the cell surface. 

PMID- 27039839
TI  - Construction of a new model of job engagement, psychological empowerment and
      perceived work environment among Chinese registered nurses at four large
      university hospitals: implications for nurse managers seeking to enhance nursing
      retention and quality of care.
AB  - AIM: To explore the relationships among perceived work environment, psychological
      empowerment and job engagement of clinical nurses in Harbin, China. BACKGROUND:
      Previous studies have focused on organisational factors or nurses' personal
      characteristics contributing to job engagement. Limited studies have examined the
      effects of perceived work environment and psychological empowerment on job
      engagement among Chinese nurses. METHOD: A cross-sectional quantitative survey
      with 923 registered nurses at four large university hospitals in China was
      carried out. Research instruments included the Chinese versions of the perceived
      nurse work environment scale, the psychological empowerment scale and the job
      engagement scale. The relationships of the variables were tested using structural
      equation modelling. RESULTS: Structural equation modelling revealed a good fit of
      the model, chi(2) /df = 4.46, GFI = 0.936, CFI = 0.957. Perceived work
      environment was a significant positive direct predictor of psychological
      empowerment and job engagement. Psychological empowerment was a significant
      positive direct contributor to job engagement and had a mediating effect on the
      relationship between perceived work environment and job engagement. CONCLUSIONS:
      Perceived work environment may result in increased job engagement by facilitating
      the development of psychological empowerment. IMPLICATIONS FOR NURSING
      MANAGEMENT: For nurse managers wishing to increase nurse engagement and to
      achieve effective management, both perceived work environment and psychological
      empowerment are factors that need to be well controlled in the process of nurse
      administration.

PMID- 27039840
TI  - Signature of coexistence of superconductivity and ferromagnetism in two
      dimensional NbSe2 triggered by surface molecular adsorption.
AB  - Ferromagnetism is usually deemed incompatible with superconductivity.
      Consequently, the coexistence of superconductivity and ferromagnetism is usually
      observed only in elegantly designed multi-ingredient structures in which the two
      competing electronic states originate from separate structural components. Here
      we report the use of surface molecular adsorption to induce ferromagnetism in two
      dimensional superconducting NbSe2, representing the freestanding case of the
      coexistence of superconductivity and ferromagnetism in one two-dimensional
      nanomaterial. Surface-structural modulation of the ultrathin superconducting
      NbSe2 by polar reductive hydrazine molecules triggers a slight elongation of the
      covalent Nb-Se bond, which weakens the covalent interaction and enhances the
      ionicity of the tetravalent Nb with unpaired electrons, yielding ferromagnetic
      ordering. The induced ferromagnetic momentum couples with conduction electrons
      generating unique correlated effects of intrinsic negative magnetoresistance and
      the Kondo effect. We anticipate that the surface molecular adsorption will be a
      powerful tool to regulate spin ordering in the two-dimensional paradigm. 

PMID- 27039841
TI  - Effect of increasing levels of wasted date palm on digestion, rumen fermentation
      and microbial protein synthesis in sheep.
AB  - This study was conducted to evaluate the effects of increasing levels of wasted
      date (WD) in sheep (initial body weight 50 +/- 2.3 kg) diets on apparent diet
      digestibility, rumen fermentation and microbial protein synthesis. The
      experimental diets contained 0 (0 WD), 9% (9 WD), 18% (18 WD) or 27% (27 WD) of
      wasted dates. These diets were evaluated through a 4 * 4 Latin square design with
      four 28-day periods. Sheep were individually housed in metabolic cages and were
      fed diets ad libitum. To keep the diets isoenergetic and isonitrogenous,
      increasing partial replacement of WD for barley grain was used with increasing
      levels of soya bean meal. Increasing the amount of WD in diets of sheep did not
      influence (p > 0.05) diet intake and digestibility of nutrients. Inclusion of WD
      in diets of sheep did not affect (p > 0.05) ruminal pH but decreased (p < 0.05)
      NH3 -N concentration and blood urea nitrogen. Also there was no effect (p > 0.05)
      of the WD provision on N intake and faecal N loss of experimental animals, but
      urinary nitrogen excretion and retained nitrogen were affected (p < 0.05) by
      dietary treatments. Purine derivatives and microbial protein synthesis increased
      (p < 0.05) linearly with the level of WD in the diet. In conclusion, the increase
      in microbial protein synthesis and concomitant reduction in ruminal NH3 -N
      concentration and blood urea nitrogen in response to wasted date supply suggest
      improved efficiency of ruminal nitrogen metabolism without adverse effects on
      fermentation characteristics and animal performance.

PMID- 27039842
TI  - Nationwide Survey of the Transfer of Adults With Congenital Heart Disease From
      Pediatric Cardiology Departments to Adult Congenital Heart Disease Centers in
      Japan.
AB  - BACKGROUND: Current Japanese transfer practices for adult congenital heart
      disease (ACHD) patients in pediatric departments are elucidated in this study.
      The focus was on 149 facilities (from the Japanese Society of Pediatric
      Cardiology and Cardiac Surgery Subspecialty Board and the Japanese Association of
      Children's Hospitals and Related Institutions). One hundred and thirteen
      facilities were surveyed and the response rate was 75.8%. METHODS AND RESULTS:
      Twenty-six facilities (23.0%) treated >=200 outpatients annually; 48 facilities
      (42.9%) treated <50 outpatients. Only eight facilities admitted >=50 inpatients;
      61 facilities (54.0%) admitted <10 inpatients. Nine facilities fulfilled
      international regional ACHD center criteria. The estimated median number of
      patients receiving outpatient pediatric department follow up was 33,806. Sixty
      facilities (53.6%) treated patients in pediatric departments after they reached
      adulthood. Of 49 facilities that transferred patients, the transfer was most
      commonly to another department in the same facility (20 facilities; 40.8%),
      typically the adult cardiology department (29 facilities; 59.2%). In future, 55
      facilities (48.7%) desired the transfer of patients to regional ACHD centers,
      while 34 facilities (30.1%) preferred to continue treating patients in the
      pediatric department. CONCLUSIONS: The number of regional ACHD centers offering
      sufficient outpatient and inpatient care is limited; transfer from pediatric
      departments is not standard in Japan. Role division clarification between
      regional ACHD centers and other facilities and cooperative network establishment
      including transitional care programs is necessary. (Circ J 2016; 80: 1242-1250).

PMID- 27039843
TI  - Announcement of the 2016 JCS Meeting Activities (2).

PMID- 27039844
TI  - rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments
      and an Extended Pathology Beyond the Central Nervous System.
AB  - Aspartoacylase (AspA) gene mutations cause the pediatric lethal neurodegenerative
      Canavan disease (CD). There is emerging promise of successful gene therapy for CD
      using recombinant adeno-associated viruses (rAAVs). Here, we report an
      intracerebroventricularly delivered AspA gene therapy regime using three
      serotypes of rAAVs at a 20-fold reduced dose than previously described in AspA(-/
      ) mice, a bona-fide mouse model of CD. Interestingly, central nervous system
      (CNS)-restricted therapy prolonged survival over systemic therapy in CD mice but
      failed to sustain motor functions seen in systemically treated mice. Importantly,
      we reveal through histological and functional examination of untreated CD mice
      that AspA deficiency in peripheral tissues causes morphological and functional
      abnormalities in this heretofore CNS-defined disorder. We demonstrate for the
      first time that AspA deficiency, possibly through excessive N-acetyl aspartic
      acid accumulation, elicits both a peripheral and CNS immune response in CD mice.
      Our data establish a role for peripheral tissues in CD pathology and serve to aid
      the development of more efficacious and sustained gene therapy for this disease.

PMID- 27039845
TI  - Randomized Phase 2 Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront
      Treatment of Metastatic Pancreatic Adenocarcinoma.
AB  - Pelareorep causes oncolysis in tumor cells with activated Ras. We hypothesized
      that pelareorep would have efficacy and immunomodulatory activity in metastatic
      pancreatic adenocarcinoma (MPA) when combined with carboplatin and paclitaxel. A
      randomized phase 2 study (NCT01280058) was conducted in treatment-naive patients
      with MPA randomized to two treatment arms: paclitaxel/carboplatin + pelareorep
      (Arm A, n = 36 evaluable patients) versus paclitaxel/carboplatin (Arm B, n = 37
      evaluable patients). There was no difference in progression-free survival (PFS)
      between the arms (Arm A PFS = 4.9 months, Arm B PFS = 5.2 months, P = 0.6), and
      Kirsten rat sarcoma viral oncogene (KRAS) status did not impact outcome. Quality
      adjusted Time without Symptoms or Toxicity analysis revealed that the majority of
      PFS time was without toxicity or progression (4.3 months). Patient
      immunophenotype appeared important, as soluble immune biomarkers were associated
      with treatment outcome (fractalkine, interleukin (IL)-6, IL-8, regulated on
      activation, normal T cell expressed and secreted (RANTES), and vascular
      endothelial growth factor (VEGF)). Increased circulating T and natural killer
      (NK)-cell subsets were also significantly associated with treatment outcome.
      Addition of pelareorep was associated with higher levels of 14 proinflammatory
      plasma cytokines/chemokines and cells with an immunosuppressive phenotype (Tregs,
      cytotoxic T lymphocyte associated protein 4 (CTLA4)(+) T cells). Overall,
      pelareorep was safe but does not improve PFS when administered with
      carboplatin/paclitaxel, regardless of KRAS mutational status. Immunologic studies
      suggest that chemotherapy backbone improves immune reconstitution and that
      targeting remaining immunosuppressive mediators may improve oncolytic
      virotherapy. 

PMID- 27039847
TI  - Epidemiological and Molecular Studies on Lumpy Skin Disease Outbreaks in Turkey
      during 2014-2015.
AB  - This study was carried out to explore epidemiological and molecular features of
      lumpy skin disease virus (LSDV) in the Aegean, Central Anatolian and
      Mediterranean regions of Turkey, to evaluate the risk factors associated with
      LSDV infection and to investigate the financial impact of LSD and potential role
      of the Culicoides spp. in the transmission of LSDV. Samples were obtained from
      611 cattle, each from different farms, and each clinically suspected to be
      infected with LSDV during the months of July 2014 and June 2015. Culicoides spp.
      were trapped from April to June 2015. Genetic characterization of the local LSDV
      field isolates was conducted by sequencing G-protein-coupled chemokine receptor
      gene segment. Real-time PCR high-resolution melting analysis was used for
      distinguishing each type of capripoxviruses. Viral DNA was detected in 448 of the
      611 animals and Culicoides midges. Three hundred and ninety-three of the 448
      affected farms were surveyed. The morbidity and mortality rates detected were
      12.3% and 6.4%, respectively. Phylogenetic analysis showed that the field
      isolates in this study were clustered together with other Africa and Middle East
      isolates. Genotyping of isolates from infected cattle has revealed the presence
      of LSDV. A generalized mixed linear model showed that there were positive
      associations between LSDV infection, European breeds, small-sized family-type
      farms and nearness of farm to a lake. The financial cost of disease presence in
      surveyed cattle farms was estimated to be 72.75 GBP per head. The sequence
      analysis of the mitochondrial cytochrome oxidase subunit I gene showed that the
      species of Culicoides in LSDV-positive pools was Culicoides punctatus. Detection
      of LSDV in Culicoides punctatus suggests that it may have played a role in
      transmitting LSDV. Furthermore, movement of infected animals into disease-free
      areas increases the risk of the transmission of LSD. Control strategies for LSDV
      infection should include consideration of the risk factors identified in this
      study.

PMID- 27039846
TI  - Predictive and Prognostic Clinical Variables in Cancer Patients Treated With
      Adenoviral Oncolytic Immunotherapy.
AB  - The development of oncolytic viruses has recently made great progress towards
      being available to cancer patients. With the breakthrough into clinics, it is
      crucial to analyze the existing clinical experience and use it as a basis for
      treatment improvements. Here, we report clinical data from 290 patients treated
      with oncolytic adenovirus. Using clinical variables and treatment
      characteristics, we constructed statistical models with regard to treatment
      response and overall survival (OS). Additionally, we investigated effects of
      neutralizing antibodies, tumor burden, and peripheral blood leucocyte counts on
      these outcomes. We found the absence of liver metastases to correlate with an
      improved rate of disease control (P = 0.021). In multivariate evaluation,
      patients treated with viruses coding for immunostimulatory granulocyte macrophage
      colony-stimulating factor were linked to better prognosis (hazard ratio (HR)
      0.378, P < 0.001), as well as women with any cancer type (HR 0.694, P = 0.017).
      In multivariate analysis for imaging response, patients treated via
      intraperitoneal injection were more likely to achieve disease control (odds ratio
      (OR) 3.246, P = 0.027). Patients with low neutrophil-to-lymphocyte ratio before
      treatment had significantly longer OS (P < 0.001). These findings could explain
      some of the variation seen in treatment outcomes after virotherapy. Furthermore,
      the results offer hypotheses for treatment optimization and patient selection in
      oncolytic adenovirus immunotherapy.

PMID- 27039849
TI  - LUIGI PROVASOLI AWARD RECIPIENTS.

PMID- 27039850
TI  - SURFACTANT PROMOTION OF THE INHIBITORY EFFECTS OF CUPRIC GLUTAMATE ON THE
      DINOFLAGELLATE ALEXANDRIUM(1).
AB  - We studied cupric glutamate as a novel algicide for marine harmful algae and
      hexadecyltrimethyleamine bromide (HDTMAB) as an accelerant. Cupric glutamate had
      an excellent ability to inhibit the growth of Alexandrium sp. LC3, but the
      inhibition efficiency did not increase with higher cupric glutamate
      concentration. The studies on the inhibition ofAlexandrium sp. LC3 by cupric
      sulfate or cupric glutamate showed that cupric glutamate had a higher inhibition
      rate than cupric sulfate (P < 0.05). HDTMAB could significantly enhance the
      inhibition by cupric glutamate (P < 0.05). Ultrastructural changes of Alexandrium
      sp. LC3 under cupric sulfate, cupric glutamate, and cupric glutamate-HDTMAB
      combined treatment were studied with TEM. Under these stresses, the integrity of
      the cell plasma membranes (cell plasma membrane, chloroplast and mitochondria
      membranes) was destroyed. The degree of damage under cupric glutamate-HDTMAB
      combined treatment was more severe than under the other stresses. These results
      indicated that mechanistically cupric glutamate inhibits algal growth by
      destroying the cell membranes, and that HDTMAB promotes this process, which
      induced mass extravasation of intracellular components and more copper ion entry
      into the plasma. 

PMID- 27039851
TI  - COLONY SIZE OF PHAEOCYSTIS ANTARCTICA (PRYMNESIOPHYCEAE) AS INFLUENCED BY
      ZOOPLANKTON GRAZERS(1).
AB  - The haptophyte Phaeocystis antarctica G. Karst. is a dominant phytoplankton
      species in the Ross Sea, Antarctica, and exists as solitary cells and
      mucilaginous colonies that differ by several orders of magnitude in size. Recent
      studies with Phaeocystis globosa suggest that colony formation and enlargement
      are defense mechanisms against small grazers. To test if a similar grazer-induced
      morphological response exists in P. antarctica, we conducted incubation
      experiments during the austral summer using natural P. antarctica and zooplankton
      assemblages. Dialysis bags that allowed exchange of dissolved chemicals were used
      to separate P. antarctica and zooplankton during incubations. Geometric mean
      colony size decreased by 35% in the control, but increased by 30% in the presence
      of grazers (even without physical contact) over the 15 d incubation. The
      estimated colonial-to-solitary cell carbon ratio was significantly higher in the
      grazing treatment. These results suggest that P. antarctica colonies would grow
      larger in the presence of indigenous zooplankton and skew the carbon partitioning
      significantly toward the colonial phase. While these observations show that the
      colony size of P. antarctica was affected by a chemical signal related to
      grazers, the detailed nature and ecological significance of this signal remain
      unknown. 

PMID- 27039848
TI  - Ethylene positively regulates cold tolerance in grapevine by modulating the
      expression of ETHYLENE RESPONSE FACTOR 057.
AB  - Ethylene (ET) is a gaseous plant hormone that plays essential roles in biotic and
      abiotic stress responses in plants. However, the role of ET in cold tolerance
      varies in different species. This study revealed that low temperature promotes
      the release of ET in grapevine. The treatment of exogenous 1-aminocyclopropane-1
      carboxylate increased the cold tolerance of grapevine. By contrast, the
      application of the ET biosynthesis inhibitor aminoethoxyvinylglycine reduced the
      cold tolerance of grapevine. This finding suggested that ET positively affected
      cold stress responses in grapevine. The expression of VaERF057, an ET signaling
      downstream gene, was strongly induced by low temperature. The overexpression of
      VaERF057 also enhanced the cold tolerance of Arabidopsis. Under cold treatment,
      malondialdehyde content was lower and superoxide dismutase, peroxidase, and
      catalase activities were higher in transgenic lines than in wild-type plants. RNA
      Seq results showed that 32 stress-related genes, such as CBF1-3, were upregulated
      in VaERF057-overexpressing transgenic line. Yeast one-hybrid results further
      demonstrated that VaERF057 specifically binds to GCC-box and DRE motifs. Thus,
      VaERF057 may directly regulate the expression of its target stress-responsive
      genes by interacting with a GCC-box or a DRE element. Our work confirmed that ET
      positively regulates cold tolerance in grapevine by modulating the expression of
      VaERF057. 

PMID- 27039852
TI  - ALKALINE PHOSPHATASE ACTIVITY AS A FUNCTION OF INTERNAL PHOSPHORUS CONCENTRATION
      IN FRESHWATER PHYTOPLANKTON(1).
AB  - Single-cell alkaline phosphatase (AP) activity is being increasingly used to
      characterize phosphorus (P) status of individual species of phytoplankton. As
      phytoplankton growth rates depend more directly on the internal rather than
      external P concentrations, we determine the AP activity in the two species of
      freshwater phytoplankton, Scenedesmus quadricauda (Turpin) Breb. and Asterionella
      formosa Hassall, as a function of internal P concentration. AP activity strongly
      correlated with cellular P, increasing almost linearly with decreasing cellular P
      in both species. The dynamics of initial responses of AP activity to P
      limitation, as well as the final levels of AP activity, when cellular P
      approached minimum quotas, differed in two species. After P addition, cellular P
      concentrations increased rapidly, but AP activity remained high for several days.
      The lag in AP activity down-regulation following an increase in cellular P made
      it difficult to infer current P status of cells under dynamic P conditions. 

PMID- 27039853
TI  - THE BIOGEOGRAPHIC ORIGIN OF ARCTIC ENDEMIC SEAWEEDS: A THERMOGEOGRAPHIC VIEW(1).
AB  - The Arctic is geologically and biogeographically young, and the origin of its
      seaweed flora has been widely debated. The Arctic littoral biogeographic region
      dates from the latest Tertiary and Pleistocene. Following the opening of Bering
      Strait, about 3.5 mya, the "Great Trans-Arctic Biotic Interchange" populated the
      Arctic with a fauna strongly dominated by species of North Pacific origin. The
      Thermogeographic Model (TM) demonstrates why climate and geography continued to
      support this pattern in the Pleistocene. Thus, Arctic and Atlantic subarctic
      species of seaweeds are likely to be evolutionarily "based" in the North Pacific,
      subarctic species are likely to be widespread in the warmer Arctic, and species
      of Atlantic Boreal or warmer origin are unlikely in the Arctic and Subarctic.
      Although Arctic seaweeds have been thought to have a greater affinity with the
      North Atlantic, we have reanalyzed the Arctic endemic algal flora, using the
      Thermogeographic Model and evolutionary trees based on molecular data, to
      demonstrate otherwise. There are 35 congeneric species of the six, abundant
      Arctic Rhodophyta that we treat in this paper; 32 of these species (91%) occur in
      the North Pacific, two species (6%) occur in the Boreal or warmer Atlantic Ocean,
      and a single species is panoceanic, but restricted to the Subarctic. Laminaria
      solidungula J. Agardh, a kelp Arctic "endemic" species, has 18 sister species.
      While only eleven (61%) occur in the North Pacific, this rapidly dispersing and
      evolving genus is a terminal member of a diverse family and order (Laminariales)
      widely accepted to have evolved in the North Pacific. Thus, both the
      physical/time-based TM and the dominant biogeographic pattern of relatives of
      Arctic macrophytes suggest strong compliance with the evidence of zoology,
      geology, and paleoclimatology that the Arctic marine flora is largely of Pacific
      origin. 

PMID- 27039854
TI  - VOLVOX BARBERI, THE FASTEST SWIMMER OF THE VOLVOCALES (CHLOROPHYCEAE)(1).
AB  - Volvox barberi W. Shaw is a volvocalean green alga composed of biflagellated
      cells. Vovocales with 16 cells or more form spherical colonies, and their largest
      members have germ-soma separation (all species in the genus Volvox). V. barberi
      is the largest Volvox species recorded in terms of cell number (10,000-50,000
      cells) and has the highest somatic to reproductive cell ratio (S/R). Since they
      are negatively buoyant, Volvocales need flagellar beating to avoid sinking and to
      reach light and nutrients. We measured V. barberi swimming speed and total
      swimming force. V. barberi swimming speeds are the highest recorded so far for
      volvocine algae (~600 MUm . s(-1) ). With this speed, V. barberi colonies have
      the potential to perform daily vertical migrations in the water column at speeds
      of 2-3 m . h(-1) , consistent with what has been reported about Volvox
      populations in the wild. Moreover, V. barberi data fit well in the scaling
      relationships derived with the other smaller Volvox species, namely, that the
      upward swimming speed Vup ?N(0.28) and the total swimming force FS ?N(0.77) (N =
      colony cell number). These allometric relationships have been important
      supporting evidence for reaching the conclusion that as size increases, colonies
      have to invest in cell specialization and increase their S/R to increase their
      motility capabilities to stay afloat and motile. 

PMID- 27039855
TI  - THE DISTRIBUTION, MORPHOLOGY, AND ECOLOGY OF THREE INTRODUCED ASIATIC SPECIES OF
      PORPHYRA (BANGIALES, RHODOPHYTA) IN THE NORTHWESTERN ATLANTIC(1).
AB  - Distributions of three Asiatic Porphyra species, Porphyra yezoensis Ueda,
      Porphyra katadae A. Miura, and Porphyra suborbiculata Kjellm., are reported from
      New England, USA. Species identifications were confirmed by rbcL and nuclear
      ribosomal DNA internal transcribed spacer-1 (ITS1) sequence comparisons with
      herbarium specimens, cultures, and GenBank accessions. Two distinct genotypes of
      P. yezoensis were detected: forma narawaensis A. Miura and f. yezoensis. Forma
      narawaensis occurs south of Cape Cod, Massachusetts, and has ITS1 sequences
      identical to cultivars widely grown in Japan. Forma yezoensis occurs in western
      Long Island Sound and from Cape Cod northward to midcoastal Maine; its ITS1
      sequence is identical to a wild specimen from Hokkaido, Japan. P. katadae has
      been collected from five locations near Cape Cod; its ITS1 sequence is identical
      to a cultured specimen from Qingdao, China. P. suborbiculata has been collected
      at several locations south of Cape Cod; its presence in North Carolina and
      Delaware during the mid-1960s was confirmed from herbarium specimens.
      Morphological and ecological characteristics for New England populations of the
      three Asiatic species were compared to original descriptions. New England P.
      yezoensis f. yezoensis is similar to Ueda's original description of Japanese
      specimens, but there are morphological differences for P. yezoensis f.
      narawaensis. In New England, f. narawaensis typically does not attain the length
      reported in Japan (max. 19 cm versus 100 cm). New England P. katadae is similar
      to Miura's original description, except for slight differences in thallus
      thickness and reproductive patterns. By contrast, New England, Japanese, and
      other populations of P. suborbiculata exhibit pronounced differences in blade
      coloration, shape and dimensions, reproductive patterns, seasonal occurrence, and
      general ecology. 

PMID- 27039856
TI  - DEWFALL AS A WATER SOURCE FREQUENTLY ACTIVATES THE ENDOLITHIC CYANOBACTERIAL
      COMMUNITIES IN THE GRANITES OF TAYLOR VALLEY, ANTARCTICA(1).
AB  - Endolithic photosynthetic microorganisms like cyanobacteria and algae are well
      known from savannas and deserts of the world, the high Arctic, and also Antarctic
      habitats like the Dry Valleys in the Ross Dependency. These endolithic microbial
      communities are thought to be at the limits of life with reported ages in the
      order of thousands of years. Here we report on an extensive chasmoendolithic
      cyanobacterial community inside granite rocks of Mt. Falconer in the lower Taylor
      Valley, Dry Valleys. On average, the cyanobacterial community was 4.49 +/- 0.95
      mm below the rock surface, where it formed a blue-green layer. The community was
      composed mainly of the cyanobacterium Chroococcidiopsis sp., with occasional
      Cyanothece cf. aeruginosa (Nageli) Komarek and Nostoc sp. Mean biomass was 168 +/
      44 g carbon . m(-2) , and the mean chl a content was 24.3 +/- 34.2 mg . m(-2) .
      In situ chl fluorescence measurements-a relative measure of photosynthetic
      activity-showed that they were active over long periods each day and also showed
      activity the next day in the absence of any moisture. Radiocarbon dating gave a
      relatively young age (175-280 years) for the community. Calculations from
      microclimate data demonstrated that formation of dew or rime was possible and
      could frequently activate the cyanobacteria and may explain the younger age of
      microbial communities at Mt. Falconer compared to older and less active
      endolithic microorganisms reported earlier from Linnaeus Terrace, a higher
      altitude region that experiences colder, drier conditions. 

PMID- 27039857
TI  - PLANOZYGOTE DIVISION AND OTHER OBSERVATIONS ON THE SEXUAL CYCLE OF SEVERAL
      SPECIES OF DINOPHYSIS (DINOPHYCEAE, DINOPHYSIALES)(1).
AB  - A life-cycle model has been proposed for Dinophysis, but several transitions
      between stages of this cycle needed more detailed description. In this study, the
      steps from mating gamete pairs, cell fusion, nuclear fusion, and the fate of
      planozygotes were tracked and described from incubations of different sexual
      cycle stages of D. acuminata Clap. et J. Lachm., D. cf. ovum F. Schutt, and D.
      acuta Ehrenb. There were several pathways for depauperating division and
      formation of small and intermediate cells; observed mating tubes that connect
      mating gamete pairs were more delicate than the feeding tube described in D.
      acuminata; nuclear fusion occurs following cell fusion. Planozygotes were able to
      divide and produce several vegetative cells 2-3 weeks after incubation. New
      pathways were added to the revised sexual life-cycle model of Dinophysis spp. It
      is hypothesized that planozygotes are the main diploid sexual stage that may be
      involved in overwintering and seeding strategies. The importance of planozygote
      division, without further maturation into a resting cyst, as an adaptive strategy
      for holoplanktonic organisms is discussed. 

PMID- 27039858
TI  - PHOTOINHIBITION IN RED ALGAL SPECIES WITH DIFFERENT CAROTENOID PROFILES(1).
AB  - Members of the Rhodophyta present different carotenoid profiles. In a majority of
      the species, lutein constitutes >50% of the total carotenoid content, while in
      other species, it is replaced by zeaxanthin or antheraxanthin. Given that
      carotenoids have specific roles in photoprotection, different carotenoid profiles
      of red algae species could be related to their capacity to cope with
      photoinhibitory stress. Therefore, in the present work, the sensitivity to light
      stress of red algal species with different carotenoid profiles was investigated.
      Photoinhibition of photosynthesis induced by high-light stress and the subsequent
      recovery in dim-light conditions was measured using maximal PSII quantum
      efficiency (Fv /Fm ). The degree of decrease and recovery of Fv /Fm and their
      respective kinetics were related to the carotenoid profile of the species.
      Although no relationship between sensitivity to high-light stress and the
      carotenoid profile was observed, there were clear carotenoid profile-related
      differences in the decrease and recovery kinetics. In species with zeaxanthin or
      antheraxanthin as the major carotenoid, Fv /Fm reduction and recovery was
      principally associated with slowly activated and relaxed processes. In contrast,
      in species with lutein as the major carotenoid, rapidly activated processes
      appear to play a major role in the down-regulation of photosynthesis during light
      stress conditions. In these species, the repair of D1 is also important during
      light-stress conditions. This finding could imply differential expression of
      mechanisms involved in photoprotection in red algae that seems to be related to
      the carotenoid profile of the species. 

PMID- 27039859
TI  - PRODUCTION OF NATURAL BUTYLATED HYDROXYTOLUENE AS AN ANTIOXIDANT BY FRESHWATER
      PHYTOPLANKTON(1).
AB  - Butylated hydroxytoluene (BHT) is one of the synthetic antioxidant agents
      commonly used for food additives. In the present study, we determined that four
      freshwater phytoplankton, including a green alga (Botryococcus braunii Kutz.) and
      three cyanobacteria [Cylindrospermopsis raciborskii (Wollosz.) Seenaya et Sabba
      Raju, Microcystis aeruginosa (Kutz.) and Oscillatoria sp.] were capable of
      producing this compound. Hexane extracts from all the studied species exhibited
      various degrees of antioxidative properties when they were tested with the beta
      carotene-linoleate (beta-CL) assay and the 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      free-radical-scavenging assay. The highest antioxidant activity was observed in
      the crude extracts of M. aeruginosa and B. braunii, which displayed a similar
      activity to synthetic BHT. Gas chromatography/mass spectroscopy (GC-MS) analysis
      of the purified fractions revealed that the active compound was identical to
      synthetic BHT. Culturing under various irradiances gave rise to different
      magnitudes of BHT production in cyanobacterial cells, showing that more BHT was
      produced in the cells irradiated with a higher light intensity, and its
      production was irradiance dependent. Moreover, the quantity of cellular BHT
      displayed a positive correlation with the antioxidative activity of the tested
      species. The present study confirms the production of BHT in all four of the
      studied freshwater phytoplankton and suggests that these species constitute a
      potential source for producing natural BHT. 

PMID- 27039860
TI  - SPECIFICITY AND FUNCTION OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IN A
      FRESHWATER DIATOM, ASTERIONELLA FORMOSA (BACILLARIOPHYCEAE)(1).
AB  - The plastidic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the only
      reductive step in the Calvin cycle and exists as different forms of which GapC1
      enzyme is present in chromalveolates, such as diatoms. Biochemical studies on
      diatoms are still fragmentary, and, thus, in this report, GAPDH from the
      freshwater diatom Asterionella formosa Hassall has been purified and kinetically
      characterized. It is a homotetrameric enzyme with a molecular mass of ~150 +/- 15
      kDa. The enzyme showed Michaelis-Menten kinetics with respect to both cofactors,
      NADPH and NADH, with a 16-fold greater catalytic constant for NADPH. The Km for
      NADPH was 140 MUM, the lowest affinity reported, while the catalytic constant,
      815 s(-1) , is the highest reported. The Km for NADH was 93 MUM, and the
      catalytic constant was 50 s(-1) , both are similar to reported values for other
      types of GAPDH. The GapC1 enzyme, like the Chlamydomonas reinhardtii A4 GAPDH,
      exhibits a cooperative behavior toward the substrate, 1,3-bisphosphoglyceric acid
      (BPGA), with both cofactors. Mass spectrometry analysis showed that when GapC1
      enzyme was purified without reducing agents, it copurified with a small protein
      with a mass of 8.2 kDa. This protein was recognized by antibodies against CP12.
      When associated with this protein, GAPDH displayed a lag that disappeared upon
      incubation with reducing agent in the presence of either BPGA or NADPH as a
      consequence of dissociation of the GAPDH/CP12 complex. Thus, as in other species
      of algae and higher plants, regulation of GapC1 enzyme in A. formosa may occur
      through association-dissociation processes linked to dark-light transitions. 

PMID- 27039861
TI  - THE COMPLEX EXTRACELLULAR POLYSACCHARIDES OF MAINLY CHAIN-FORMING FRESHWATER
      DIATOM SPECIES FROM EPILITHIC BIOFILMS(1).
AB  - Diatoms are dominant organisms in phototrophic biofilms in aquatic habitats. They
      produce copious amounts of extracellular polymeric substances (EPS), which mainly
      consist of carbohydrates and traces of proteins and glycoproteins. This study
      focuses on the characterization of EPS from a total of 14 diatoms belonging to
      the six genera Achnanthes, Cymbella, Fragilaria, Punctastriata, Staurosira, and
      Pseudostaurosira, all of which were isolated from epilithic biofilms of the
      littoral zone of Lake Constance. EPS from all isolates were extracted by a
      sequential extraction procedure resulting in five different fractions. The
      monosaccharide composition of each fraction was analyzed by HPLC equipped with a
      pulse amperiometric detector, yielding results similar to those obtained by
      probing the EPS structures with monomer-specific fluorophore-linked lectins.
      Significant differences in carbohydrate composition occurred in the different
      fractions of single isolates. Most of the diatom isolates in our study form chain
      like colonies in which the cells are attached to each other by intercellular
      pads. Here we demonstrate that these pads can be dissolved in hot bicarbonate and
      that they show a heterogeneous composition of monosaccharides in contrast to
      other fractions, which mostly were dominated by one or two monosaccharides.
      Principal component analysis indicates a correlation between carbohydrate
      composition of EPS fractions and the phylogenetic relationship of the respective
      species, indicating that EPS analyses under defined culture conditions may
      support taxonomic analyses. 

PMID- 27039862
TI  - MULTIPLE FtsZ RING FORMATION AND REDUPLICATED CHLOROPLAST DNA IN NANNOCHLORIS
      BACILLARIS (CHLOROPHYTA, TREBOUXIOPHYCEAE) UNDER PHOSPHATE-ENRICHED CULTURE(1).
AB  - We examined the effects of phosphate enrichment on chloroplasts of the
      unicellular green alga Nannochloris bacillaris Naumann. The doubling time of
      cells was similar in phosphate-limited (no beta-glycerophosphate) and phosphate
      enriched (2 mM beta-glycerophosphate) media. The lengths of cells and
      chloroplasts were similar, regardless of phosphate concentration. The
      relationship between the ring formation of the prokaryote-derived chloroplast
      division protein FtsZ and phosphate concentration was examined using indirect
      fluorescent antibody staining. The number of FtsZ rings increased as the
      phosphate concentration of the medium increased. Multiple FtsZ rings were formed
      in cells in phosphate-enriched medium; up to six FtsZ rings per chloroplast were
      observed. The number of FtsZ rings increased as the chloroplast grew. The FtsZ
      ring located near the center of the chloroplast had the strongest fluorescence.
      The FtsZ ring at the relative center of all FtsZ rings was used for division.
      Plastid division rings did not multiply in phosphate-enriched culture. The
      chloroplast DNA content was 2.3 times greater in phosphate-enriched than in
      phosphate-limited culture and decreased in cells cultured in phosphate-enriched
      medium containing 5-fluorodeoxyuridine (FdUr). In the presence of FdUr, only one
      FtsZ ring formed, even under phosphate enrichment. This finding suggests that
      excessive chloroplast DNA replication induces multiple FtsZ ring formation in
      phosphate-enriched culture. We propose a multiple FtsZ ring formation model under
      phosphate enrichment. 

PMID- 27039863
TI  - PHYTOPLANKTON COMMUNITY COMPOSITION AND GENE EXPRESSION OF FUNCTIONAL GENES
      INVOLVED IN CARBON AND NITROGEN ASSIMILATION(1).
AB  - A functional gene microarray was developed and used to investigate phytoplankton
      community composition and gene expression in the English Channel. Genes encoding
      the CO2 -fixation enzyme RUBISCO (rbcL) and the nitrate assimilation enzyme
      nitrate reductase (NR) representing several major groups of phytoplankton were
      included as oligonucleotide probes on the "phytoarray." Five major groups of
      eukaryotic phytoplankton that possess the Type 1D rbcL gene were detected, both
      in terms of presence (DNA) and activity (rbcL gene expression). Changes in
      relative signal intensity among the Type 1D rbcL probes indicated a shift from
      diatom dominance in the spring bloom to dominance by haptophytes and flagellates
      later in the summer. Because of the limitations of a smaller database, NR probes
      detected fewer groups, but due to the greater diversity among known NR sequences,
      NR probes provided higher phylogenetic resolution than did rbcL probes and
      identified two uncultivated diatom phylotypes as the most abundant (DNA) and
      active (NR gene expression) in field samples. Unidentified chlorophytes and the
      diatom Phaeodactylum tricornutum Bohlin were detected at both the DNA and cDNA
      (gene expression) levels. The reproducibility of the array was evaluated in
      several ways, and future directions for further improvement of probe development
      and sensitivity are outlined. The phytoarray provides a relatively high
      resolution, high-throughput approach to assessing phytoplankton community
      composition in marine environments. 

PMID- 27039864
TI  - PARTICIPATION OF EXTRACELLULAR NUCLEOTIDES IN THE WOUND RESPONSE OF DASYCLADUS
      VERMICULARIS AND ACETABULARIA ACETABULUM (DASYCLADALES, CHLOROPHYTA)(1).
AB  - As assayed by fluorescent reporter dyes, nitric oxide (NO) and H2 O2 , two
      downstream signaling agents induced by wounding in the alga Dasycladus
      vermicularis (Scop.) Krasser, can also be induced in unwounded Dasycladus cells
      by MUM Adenosine 5'[gamma-thio]triphosphate (ATPgammaS) and Adenosine 5'-[beta
      thio]diphosphate (ADPbetaS), but not by Adenosine 5'-O-thiomonophosphate (AMPS).
      These nucleotide-induced responses are blocked by pyridoxalphosphate-6-azophenyl
      2',4'-disulphonic acid (PPADS), an antagonist of animal purinoceptors, and by
      adenosine, a feed-back inhibitor of extracellular nucleotide responses in
      animals. Similar nucleotide- and nucleotide-antagonist responses were observed in
      Acetabularia acetabulum (L.) P. C. Silva. Significant levels of ATP released from
      Dasycladus cells were measured at wound sites by a sensitive luciferin-luciferase
      assay. Additionally, the normal wound-induced production of NO and H2 O2 in
      Dasycladus can be blocked by pretreating the cells with PPADS. Our results
      indicate that nucleotides released from wounds can serve as a signal to trigger
      wound responses in algae, and that coordinated signaling between extracellular
      nucleotides and the NO pathway may have been established early during the
      evolution of plants. 

PMID- 27039865
TI  - SCANNING ELECTRON MICROSCOPY OBSERVATIONS OF DEFORMITIES IN SMALL PENNATE DIATOMS
      EXPOSED TO HIGH CADMIUM CONCENTRATIONS(1).
AB  - Different types of malformations are likely to affect the morphology of diatoms
      when exposed to particularly unstable environmental conditions, the most easily
      identifiable being distortion of the whole frustule. In the present study, we
      investigated, by means of SEM, valve abnormalities induced by high cadmium
      contamination (100 MUg . L(-1) ) in small pennate diatoms. Changes in the shape
      of Amphora pediculus (Kutz.) Grunow and anomalous sculpturing of the cell wall of
      many species, such as Encyonema minutum (Hilse) D. G. Mann, Mayamaea agrestris
      (Hust.) Lange-Bert., Gomphonema parvulum (Kutz.) Kutz., or Eolimna minima
      (Grunow) Lange-Bert., were observed, which were not, or almost not, noticeable in
      the LM. With consideration to current knowledge of diatom morphogenesis, metal
      uptake by the cell would induce, directly or indirectly, damage to many
      cytoplasmic components (e.g., microtubules, cytoskeleton, Golgi-derived vesicles)
      involved in the precisely organized silica deposition. This study confirms that
      many species, whatever their size, are likely to exhibit morphological
      abnormalities under cadmium stress, and that this indicator may be valuable for
      the biomonitoring of metal contamination, even if SEM observations are not
      necessary for routine studies. 

PMID- 27039866
TI  - THE UTILITY OF PROTEOMICS IN ALGAL TAXONOMY: BOSTRYCHIA RADICANS/B. MORITZIANA
      (RHODOMELACEAE, RHODOPHYTA) AS A MODEL STUDY(1).
AB  - A comparison of the proteome of eight genetically well-characterized isolates of
      the Bostrychia radicans (Mont.) Mont./B. moritziana (Sond. ex Kutz.) J. Agardh
      species complex was undertaken to establish if genetic relationships among them
      can be determined using proteome data. Genetic distances were calculated on the
      basis of common and distinct spots in two-dimensional gel electrophoresis (2-DE).
      Proteomes of the male and female plants of each population were compared to
      analyze the range of genetic difference within an isolate. Haploid male and
      female plants of the same species had 3.7%-7.1% sex-specific proteins. The degree
      of similarity of the proteome was consistent with previous DNA sequence data and
      sexual compatibility studies between the isolates. Two sexually compatible
      isolates from Venezuela showed a pair-wise distance ranging from 0.14 to 0.21.
      The isolates from Mexico and Venezuela, which were partially compatible, showed a
      maximum pair-wise distance of 0.26. A high level of genetic difference was found
      among isolates that were sexually incompatible. The isolate from Brazil was
      reproductively isolated from the Mexico and Venezuela isolates and showed a
      maximum pair-wise distance of 0.65 and 0.58, respectively. Comparative proteomics
      may be helpful for studying genetic distances among algal samples, if
      intraisolate variation (gene expression) can be minimized or tested. 

PMID- 27039867
TI  - DISTRIBUTION, MORPHOLOGY, AND PHYLOGENY OF KLEBSORMIDIUM (KLEBSORMIDIALES,
      CHAROPHYCEAE) IN URBAN ENVIRONMENTS IN EUROPE(1).
AB  - Klebsormidium is a cosmopolitan genus of green algae, widespread in terrestrial
      and freshwater habitats. The classification of Klebsormidium is entirely based on
      morphological characters, and very little is understood about its phylogeny at
      the species level. We investigated the diversity and phylogenetic relationships
      of Klebsormidium in urban habitats in Europe by a combination of approaches
      including examination of field-collected material, culture experiments conducted
      in many different combinations of factors, and phylogenetic analyses of the rbcL
      gene. Klebsormidium in European cities mainly occurs at the base of old walls,
      where it may produce green belts up to several meters in extent. Specimens from
      different cities showed a great morphological uniformity, consisting of long
      filaments 6-9 MUm in width, with thin-walled cylindrical cells and smooth wall,
      devoid of false branches, H-shaped pieces, and biseriate parts. Conversely, the
      rbcL phylogeny showed a higher genetic diversity than expected from morphology.
      The strains were separated in four different clades supported by high bootstrap
      values and posterior probabilities. In culture, these clades differed in several
      characters, such as production of a superficial hydro-repellent layer, tendency
      to break into short fragments, and inducibility of zoosporulation. On the basis
      of the taxonomic information available in the literature, most strains could not
      be identified unambiguously at the species level. The rbcL phylogeny showed no
      correspondence with classification based on morphology and suggested that the
      identity of many species, in particular the type species K. flaccidum (kutz.)
      P.C. Silva, Mattox et W. H. Blackw., needs critical reassessment. 

PMID- 27039868
TI  - TAXONOMIC REVISION OF SARGASSUM (FUCALES, PHAEOPHYCEAE) FROM FRENCH POLYNESIA
      BASED ON MORPHOLOGICAL AND MOLECULAR ANALYSES(1).
AB  - An assessment of Sargassum in French Polynesia was done through the critical
      revision of the literature, type specimens, and specimens from type localities.
      Sargassum samples were newly collected, and four morphotypes were identified on
      the basis of morphological characters. Molecular analysis of the nuclear ITS2,
      chloroplastic partial rbcLS, and mitochondrial cox3 markers generated two clades
      and confirmed the recent divergence suspected between closely related species.
      Although 18 different epithets have been attributed to French Polynesian
      Sargassum since 1828, only three species are considered valid in this study. Most
      of these species were transferred to S. pacificum Bory, the only species present
      in the Society Archipelago, while S. obtusifolium J. Agardh was restricted to the
      Austral Archipelago, and S. echinocarpum J. Agardh was confirmed for the Austral
      and Gambier Archipelagos. A morphological identification key is provided, along
      with descriptions and illustrations for each polymorphic species. Moreover, the
      study of several regional collections underlined similar and low specific
      diversity among Sargassum populations in the southeastern Pacific. As a result of
      this study, we propose that S. bacciferum J. Agardh var. latiuscula Grunow, S.
      bisserula f. pacifica Grunow, S. boraborense (Grunow) Setch., S. mangarevense
      (Grunow) Setch., S. sociale (Grunow) Setch., and S. tahitense Grunow be
      considered as heterotypic synonyms of S. pacificum. Sargassum skottsbergii
      Sjostedt, S. hawaiiensis Doty et Newhouse, S. divaricatum var. chilensis Grunow,
      S. obtusifolium J. Agardh f. chamberlainii Grunow, and S. obtusifolium J. Agardh
      f. lendigeroides Grunow are further regarded as heterotypic synonyms of S.
      obtusifolium. 

PMID- 27039869
TI  - PHYLOGENETIC ANALYSES OF THE RED ALGAL ORDER RHODYMENIALES SUPPORTS RECOGNITION
      OF THE HYMENOCLADIACEAE FAM. NOV., FRYEELLACEAE FAM. NOV., AND NEOGASTROCLONIUM
      GEN. NOV.(1).
AB  - Systematics of the red algal order Rhodymeniales was investigated using combined
      large-subunit nuclear ribosomal DNA (LSU) and elongation factor 2 (EF2) analyses.
      These data were subjected to distance, parsimony, and Bayesian analyses, and the
      resulting phylogenies were largely congruent with previously published SSU
      results in that the four currently recognized rhodymenialean families
      (Champiaceae, Faucheaceae, Lomentariaceae, and Rhodymeniaceae) were resolved as
      monophyletic lineages (with the exception of Coelothrix, which is here
      transferred to the Champiaceae from the Rhodymeniaceae). In addition, taxa
      presently considered as incertae sedis consisted of two lineages (Fryeella
      lineage and Hymenocladia lineage). Based on these results, two new families are
      proposed: (i) the Fryeellaceae fam. nov. to accommodate the genera Fryeella,
      Hymenocladiopsis, and a new taxon from Tasmania, Australia; and (ii) the
      Hymenocladiaceae fam. nov., to accommodate Asteromenia, Hymenocladia, and
      Erythrymenia. In addition to resolving familial relationships, these analyses
      resolved some novel interspecific affinities, and we propose a new genus,
      Neogastroclonium gen. nov., for Gastroclonium subarticulatum, a species that
      differs significantly in both morphology and molecular data from genuine species
      of Gastroclonium. Relationships among additional faucheacean and lomentariacean
      taxa were investigated using LSU data only, and these results are discussed. The
      familial classification of the Rhodymeniales proposed herein is discussed in
      light of vegetative and reproductive anatomy, most notably the ontogeny of the
      tetrasporangia. 

PMID- 27039870
TI  - COLEOFASCICULUS GEN. NOV. (CYANOBACTERIA): MORPHOLOGICAL AND MOLECULAR CRITERIA
      FOR REVISION OF THE GENUS MICROCOLEUS GOMONT(1).
AB  - Species currently classified within the cyanobacterial genus Microcoleus were
      determined to fall into two distinct clades in a 16S rDNA phylogeny, one
      containing taxa within the Oscillatoriaceae, the other containing taxa within the
      Phormidiaceae. The two lineages were confirmed in an analysis of the 16S-23S
      internal transcribed spacer (ITS) region sequences and secondary structures. The
      type species for Microcoleus is M. vaginatus Gomont, and this taxon belongs in
      the Oscillatoriaceae. Consequently, Microcoleus taxa in the Phormidiaceae must be
      placed in separate genera, and we propose the new genus Coleofasciculus to
      contain marine taxa currently placed in Microcoleus. The type species for
      Coleofasciculus is the well-studied and widespread marine mat-forming species
      Microcoleus chthonoplastes (Mert.) Zanardini ex Gomont. Other characters
      separating the two families include type of cell division and thylakoid
      structure. 

PMID- 27039871
TI  - NEW STREPTOPHYTE GREEN ALGAE FROM TERRESTRIAL HABITATS AND AN ASSESSMENT OF THE
      GENUS INTERFILUM (KLEBSORMIDIOPHYCEAE, STREPTOPHYTA)(1).
AB  - Sarcinoid aeroterrestrial green algae were isolated from three arid locations in
      Ukraine and the Czech Republic. Although gross morphology suggested an affinity
      with Desmococcus (for taxonomic authorities, see Table S1 in the supplementary
      material), the cellular morphological characteristics were reminiscent of those
      of Geminella terricola. However, the presence of a complex of ultrastructural
      features indicated that these isolates were members of the streptophyte lineage
      in the green plants. 18S rDNA sequence phylogenies provided evidence of a close
      relationship with Klebsormidium in the Streptophyta, while the position of
      Desmococcus was within the Trebouxiophyceae. In the internal transcribed spacer
      (ITS) rDNA phylogeny, the sarcinoid isolates were closely related with strains of
      G. terricola and Interfilum paradoxum. Strains of that clade were morphologically
      united by a specific type of cell division that involves the association of
      persistent, cap-shaped remains of the mother cell wall with daughter cells.
      Consequently, these strains were assigned to a redefined genus Interfilum, and a
      new species, I. massjukiae, was described to accommodate one of the sarcinoid
      isolates. As the position of the genus Geminella was in the Trebouxiophyceae, the
      streptophyte G. terricola was transferred to Interfilum, as I. terricola comb.
      nov., but the ITS rDNA analyses proved inconclusive to resolve its affinities
      with other species of Interfilum due to intragenomic polymorphisms. The species
      of Interfilum had a closer relationship with K. flaccidum than with other species
      of Klebsormidium. The latter genus may not be monophyletic in its present
      circumscription. 

PMID- 27039872
TI  - USE OF PULSE-AMPLITUDE-MODULATED FLUORESCENCE TO ASSESS THE PHYSIOLOGICAL STATUS
      OF CLADOPHORA SP. ALONG A WATER QUALITY GRADIENT(1).
AB  - This study investigated the application of pulse-amplitude-modulated (PAM)
      fluorometry as a rapid assessment of benthic macroalgal physiological status.
      Maximum quantum efficiency (Fv /Fm ), dark-light induction curves, and rapid
      fluorescence light-response curves (RLC) were measured on the filamentous
      macroalgal Cladophora sp. from Lake Ontario on 5 d at 16 sites spanning a
      gradient of light and nutrient supply. For Cladophora sp. growing in situ, light
      limitation was assessed by comparing average daily irradiance with the light
      utilization efficiency parameter (alpha) derived from RLCs. In this study, there
      was a nonlinear relationship between Fv /Fm and the degree of P limitation in
      macroalgae. However, only light-saturated Cladophora sp. showed a significant
      positive linear relationship between Fv /Fm and P nutrient status. The absence of
      this relationship among light-limited algae indicates that their photosynthetic
      rate would be stimulated by increased water clarity, and not by increased P
      supply. PAM fluorescence measures were successfully able to identify light
      saturated macroalgae and, among these, assess the degree to which they were
      nutrient limited. These results enable us to test hypotheses arising from numeric
      models predicting the impact of changes in light penetration and nutrient supply
      on benthic primary production. 

PMID- 27039873
TI  - AXENIC CULTIVATION OF THE HETEROTROPHIC DINOFLAGELLATE PFIESTERIA SHUMWAYAE AND
      OBSERVATIONS ON FEEDING BEHAVIOR(1).
AB  - Pfiesteria shumwayae Glasgow et J. M. Burkh. [=Pseudopfiesteria shumwayae
      (Glasgow et J. M. Burkh.) Litaker, Steid., P. L. Mason, Shields et P. A. Tester]
      is a heterotrophic dinoflagellate commonly found in temperate, estuarine waters.
      P. shumwayae can feed on other protists, fish, and invertebrates, but research on
      the biochemical requirements of this species has been restricted by the lack of
      axenic cultures. An undefined, biphasic culture medium was formulated that
      supported the axenic growth of two of three strains of P. shumwayae. The medium
      contained chicken egg yolk as a major component. Successful growth depended on
      the method used to sterilize the medium, and maximum cell yields (10(4)  . mL(-1)
      ) were similar to those attained in previous research when P. shumwayae was
      cultured with living fish or microalgae. Additionally, P. shumwayae flagellate
      cells ingested particles present in the biphasic medium, allowing detailed
      observations of feeding behavior. This research is an initial step toward a
      chemically defined axenic culture medium and determination of P. shumwayae
      metabolic requirements. 

PMID- 27039874
TI  - JOURNAL OF PHYCOLOGY REVIEWERS.

PMID- 27039876
TI  - Unusual Manifestations of Familial Juvenile Colloid Milium in Two Siblings.
AB  - Juvenile colloid milium is an extremely rare degenerative dermatosis of the
      dermal connective tissue manifesting before puberty. This chronic skin condition,
      detected primarily in sun-exposed areas, is clinically characterized by the
      development of translucent, yellowish papules and plaques containing gelatinous
      material and by the presence of eosinophilic, fissured material in the papillary
      dermis. We present two cases of juvenile colloid milium, in a 13-year-old girl
      and her 10-year-old brother; the condition emerged in both at approximately 6
      years of age and progressively worsened. They both presented with multiple
      yellowish, translucent, firm, flat papules and plaques mainly over the face on
      the cheeks and on the perioral and periocular areas in a unique linear pattern.

PMID- 27039875
TI  - Vaccinology in the third millennium: scientific and social challenges.
AB  - The epidemiology of deaths due to vaccine-preventable diseases has been
      significantly and positively altered through the use of vaccines. Despite this,
      significant challenges remain in vaccine development and use in the third
      millennium. Both new (Ebola, Chikungunya, Zika, and West Nile) and re-emerging
      diseases (measles, mumps, and influenza) require the development of new or next
      generation vaccines. The global aging of the population, and accumulating numbers
      of immunocompromised persons, will require new vaccine and adjuvant development
      to protect large segments of the population. After vaccine development,
      significant challenges remain globally in the cost and efficient use and
      acceptance of vaccines by the public. This article raises issues in these two
      areas and suggests a way forward that will benefit current and future
      generations.

PMID- 27039877
TI  - Emergence of ferroelectricity in antiferroelectric nanostructures.
AB  - First-principles-based finite-temperature simulations are used to predict the
      emergence of ferroelectricity in antiferroelectric nanostructures made of PbZrO3.
      The phenomenon is expected to occur in antiferroelectric nanodots, nanowires, and
      thin films with good surface charge compensation and can be explained by the
      recently proposed surface effect. Our computations provide a microscopic insight
      into the equilibrium phases, phase competition, and electrical properties of
      PbZrO3 nanostructures. The dependence of these properties on the electrical
      boundary conditions and nanostructure size is investigated.

PMID- 27039878
TI  - Narrow endemics on coastal plains: Miocene divergence of the critically
      endangered genus Avellara (Compositae).
AB  - Critically endangered species representing ancient, evolutionarily isolated
      lineages must be given priority when allocating resources for conservation
      projects. Sound phylogenetic analyses and divergence time estimations are
      required to detect them, and studies on their population genetics, ecological
      requirements and breeding system are needed to understand their evolutionary
      history and to design efficient conservation strategies. Here we present the
      paradigmatic case of Avellara, a critically endangered monotypic genus of
      Compositae inhabiting a few swamps in the west-southwest Iberian coastal plains.
      Our phylogenetic and dating analyses based on nuclear (ITS) and plastid (matK)
      DNA sequences support a Miocene (>8.6 Ma) divergence between Avellara and closely
      related genera, resulting in marked morphological and ecological differentiation.
      We found alarmingly low levels of genetic diversity, based on AFLPs and plastid
      DNA sequences, and confirmed the prevalence of clonal reproduction. Species
      distribution modelling suggested a large macroclimatically suitable area for
      Avellara in the western Iberian Peninsula, but its apparently narrow
      microecological requirements restrict its distribution to peatlands with low
      mineralised waters. Although five populations have been recorded from Spain and
      Portugal in the past, its current distribution may be reduced to only one
      population, recurrently found in the last decade but threatened by herbivory and
      habitat degradation. All this confirms the consideration of Avellara as a
      threatened species with high phylogenetic singularity, and makes it a flagship
      species for plant conservation in both Spain and Portugal that should be given
      priority in the design of in situ and ex situ conservation programmes. 

PMID- 27039879
TI  - The crystallization of metal soaps and fatty acids in oil paint model systems.
AB  - The formation and crystallization of metal soaps in oil paint layers is an
      important issue in the conservation of oil paintings. The chemical reactions and
      physical processes that are involved in releasing metal ions from pigments and
      fatty acids from the oil binder to form crystalline metal soap deposits have so
      far remained poorly understood. We have used a combination of differential
      scanning calorimetry (DSC) and attenuated total reflection Fourier transform
      infrared spectroscopy (ATR-FTIR) on model mixtures of palmitic acid, lead
      palmitate or zinc palmitate and linseed oil to study the transition from
      amorphous material to crystalline fatty acid or metal soap. This transition forms
      the final stage in the cascade of processes leading to metal soap-related oil
      paint degradation. Palmitic acid as well as the metal soaps showed nearly ideal
      solubility behavior. However, it was found that, near room temperature, both lead
      and zinc palmitate are practically insoluble in both liquid and partially
      polymerized linseed oil. Interestingly, the rate of metal soap and fatty acid
      crystallization decreased rapidly with the degree of linseed oil polymerization,
      possibly leading to systems where metal soaps are kinetically trapped in a semi
      crystalline state. To explain the various morphologies of metal soap aggregates
      observed in oil paint layers, it is proposed that factors affecting the
      probability of crystal nucleation and the rate of crystal growth play a crucial
      role, like exposure to heat or cleaning solvents and the presence of microcracks.

PMID- 27039880
TI  - The utility of indocyanine green near infrared fluorescent imaging in the
      identification of parathyroid glands during surgery for primary
      hyperparathyroidism.
AB  - BACKGROUND AND OBJECTIVES: Intraoperative adjuncts for the localization of
      parathyroid glands in parathyroid surgery are limited. The aim of this study is
      to assess the usefulness of indocyanine green (ICG) near-infrared (NIR)
      fluorescent imaging in patients undergoing surgery for primary
      hyperparathyroidism (PHPT). METHODS: ICG imaging was performed in 33 patients
      undergoing parathyroidectomy (PTX). Thyroid and parathyroid ICG uptake were
      assessed and independently verified on a grading scale. Clinical variables were
      recorded and analyzed for factors associated with ICG uptake. RESULTS: Of 112
      glands identified by naked eye, 104 (92.9%) demonstrated ICG uptake. Concomitant
      ICG fluorescence was identified in the thyroid in all patients. There was a trend
      toward increased ICG fluorescence in patients <60 years of age (P = 0.05). A
      higher degree of fluorescence was seen in patients presenting with pre-operative
      calcium values >11 mg/dl (P = 0.04) and in those parathyroids larger than 10 mm
      (P < 0.01). All patients had biochemically proven cure. No patients who underwent
      subtotal PTX (n = 6) developed postoperative hypoparathyroidism. CONCLUSION: ICG
      can reliably localize parathyroid glands during PTX and additionally allow for
      assessment of parathyroid perfusion in patients undergoing subtotal resection.
      Concomitant fluorescence of the thyroid gland limits ICG's usefulness in
      directing the course of PTX. J. Surg. Oncol. 2016;113:771-774. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27039881
TI  - Tropical Skin Diseases in Children: A Review-Part II.
AB  - Tropical skin diseases are infectious conditions influenced by factors such as
      nutrition, housing, and the environment. Migration patterns have caused these
      conditions to be seen all around the world, not only in developing countries.
      Many of these diseases have a different presentation in childhood, which changes
      the diagnostic approach and management options. In this article, we review some
      of the most common tropical mycobacterial, protozoan, parasitic, and viral
      dermatologic conditions in children, including their epidemiologic, clinical,
      diagnostic, and therapeutic aspects. 

PMID- 27039882
TI  - trans-Heteroleptic carboxylate-bridged paddlewheel diruthenium(ii, ii) complexes
      with 2,6-bis(trifluoromethyl)benzoate ligands.
AB  - Carboxylate-ligand substitution reactions of paddlewheel-type diruthenium(ii,
      iii) complexes ([Ru(RCO2)4](+)) with 2,6-bis(trifluoromethyl)benzoate (2,6
      (CF3)2PhCO2(-)) involving a selective reduction to [Ru] provide a series of trans
      substituted paddlewheel-type diruthenium(ii, ii) complexes, [Ru(2,6
      (CF3)2PhCO2)2(RCO2)2(THF)2] (R = CH3, ; C2H5, ; C3H7, ; C4H9, ; C(CH3)3, ;
      2,3,5,6-F4Ph, ). Crystal structures of were determined, and their electronic
      states were investigated by cyclic voltammetry, density functional theory (DFT)
      and magnetic measurements. This is the first example of trans-heteroleptic
      carboxylate-bridged [Ru] complexes.

PMID- 27039883
TI  - Persistence of nasal colonisation with methicillin resistant Staphylococcus
      aureus CC398 among participants of veterinary conferences and occurrence among
      their household members: A prospective cohort study, Germany 2008-2014.
AB  - There are only few data on the persistence and transmission of methicillin
      resistant Staphylococcus aureus (MRSA) of the clonal complex (CC) 398 among
      veterinarians and their household members. We therefore investigated the long
      term colonisation with MRSA CC398 among participants of veterinary conferences in
      Germany in 2008/2009 and their household members. Forty-five initially MRSA CC398
      positive and 180 initially MRSA CC398 negative conference participants were
      included in a longitudinal study. These persons and their household members were
      tested for nasal colonisation in 2011, 2012 and 2014. Of 31 continuously tested
      and initially MRSA CC398 positive participants only 8 (26%) were colonized with
      MRSA CC398at all 4 time points, 4 (13%) of them consistently with the same spa
      type. Among initially MRSA CC398 negative participants, 13 (7%) were tested MRSA
      CC398 positive at least once during the follow-up period. Data for household
      members at least at one time point were available for 185 households. Of these 21
      (11%) households had one or more household member who tested positive for MRSA
      CC398at least once. The odds of household members to be MRSA CC398 positive was
      12 times higher (95% confidence interval 4-37) when the conference participant
      tested MRSA CC398 positive in 2008/2009. This association remained strong when
      household members working in veterinary medicine or livestock farms were
      excluded. In summary, these data suggest that colonisation with MRSA CC398 is
      partially transient and that household members of MRSA CC398 colonized persons
      are at an increased risk of colonisation with MRSA CC398.

PMID- 27039884
TI  - Effect of lactoferrin on release and bioactivity of Shiga toxins from different
      Escherichia coli O157:H7 strains.
AB  - Prevention of enterohemorrhagic Escherichia coli (EHEC) O157:H7 infections and of
      their severe clinical sequelae in humans remain to be a current challenge.
      Administration of bovine lactoferrin (bLF) proved to be effective in clearing
      EHEC from the bovine intestine, an important EHEC reservoir, suggesting that bLF
      may also be beneficial in human application against EHEC infections. To estimate
      the biological safety of this approach, we analyzed the effects of bLF on the
      main EHEC virulence factor, Shiga toxin (Stx). We quantified the release of Stx 1
      and 2 from two O157:H7 EHEC strains (Stx1+Stx2+ and Stx2+ producing,
      respectively) cultured in the presence of bLF using ELISA assays and assessed
      cytotoxic effects of bLF and co-cultured EHEC on Vero cells. Effects of bLF on
      the stability of Stx2 were investigated using western blotting. ELISA results
      indicate a bLF concentration-dependent decrease of active, cell-free Stx2, but
      not Stx1 in EHEC cultures. High concentrations (100 and 50mg/ml) of bLF resulted
      in significantly reduced (p<0.05) metabolic activity rates of Vero cells, whereas
      a concentration of 10mg/ml bLF was considered non-toxic for Vero cells. At
      concentrations of 1 or 0.1mg/ml, bLF mitigated the verocytotoxicity of EHEC
      strains in a co-culture model up to 48h after inoculation. When only colonizing
      bacteria were taken into account, cytotoxicity could be significantly reduced by
      10 and 1mg/ml bLF during 48h. This effect of bLF at least partly results from
      degradation of the Stx2 receptor-binding B-subunit.

PMID- 27039885
TI  - Regenerative function of immune system: Modulation of muscle stem cells.
AB  - Ageing is characterised by progressive deterioration of physiological systems and
      the loss of skeletal muscle mass is one of the most recognisable, leading to
      muscle weakness and mobility impairments. This review highlights interactions
      between the immune system and skeletal muscle stem cells (widely termed satellite
      cells or myoblasts) to influence satellite cell behaviour during muscle
      regeneration after injury, and outlines deficits associated with ageing. Resident
      neutrophils and macrophages in skeletal muscle become activated when muscle
      fibres are damaged via stimuli (e.g. contusions, strains, avulsions,
      hyperextensions, ruptures) and release high concentrations of cytokines,
      chemokines and growth factors into the microenvironment. These localised
      responses serve to attract additional immune cells which can reach in excess of
      1*10(5) immune cell/mm(3) of skeletal muscle in order to orchestrate the repair
      process. T-cells have a delayed response, reaching peak activation roughly 4 days
      after the initial damage. The cytokines and growth factors released by activated
      T-cells play a key role in muscle satellite cell proliferation and migration,
      although the precise mechanisms of these interactions remain unclear. T-cells in
      older people display limited ability to activate satellite cell proliferation and
      migration which is likely to contribute to insufficient muscle repair and,
      consequently, muscle wasting and weakness. If the factors released by T-cells to
      activate satellite cells can be identified, it may be possible to develop
      therapeutic agents to enhance muscle regeneration and reduce the impact of muscle
      wasting during ageing and disease. 

PMID- 27039886
TI  - Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in
      transgenic mouse models of Alzheimer's disease.
AB  - It is now well established, at least in animal models, that exercise elicits
      potent pro-cognitive and pro-neurogenic effects. Alzheimer's disease (AD) is one
      of the leading causes of dementia and represents one of the greatest burdens on
      healthcare systems worldwide, with no effective treatment for the disease to
      date. Exercise presents a promising non-pharmacological option to potentially
      delay the onset of or slow down the progression of AD. Exercise interventions in
      mouse models of AD have been explored and have been found to reduce amyloid
      pathology and improve cognitive function. More recent studies have expanded the
      research question by investigating potential pro-neurogenic and anti-inflammatory
      effects of exercise. In this review we summarise studies that have examined
      exercise-mediated effects on AD pathology, cognitive function, hippocampal
      neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore,
      we attempt to identify the optimum exercise conditions required to elicit the
      greatest benefits, taking into account age and pathology of the model, as well as
      type and duration of exercise. 

PMID- 27039888
TI  - Cyclometalated iridium(III) complexes as mitochondria-targeted anticancer agents.
AB  - Four cyclometalated iridium(III) complexes [Ir(dfppy)2(L)](+) (dfppy = 2-(2,4
      difluorophenyl)pyridine, L = 6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine, Ir1; 6
      (isoquinolin-1-yl)-1,3,5-triazine-2,4-diamine, Ir2; 6-(quinolin-2-yl)-1,3,5
      triazine-2,4-diamine, Ir3; 6-(isoquinolin-3-yl)-1,3,5-triazine-2,4-diamine, Ir4)
      have been synthesized and characterized. Distinct from cisplatin, Ir1-Ir4 could
      specifically target mitochondria and induced apoptosis against various cancer
      cell lines, especially for cisplatin resistant cells. ICP-MS results indicated
      that Ir1-Ir4 were taken up via different mechanism for cancer cells and normal
      cells, which resulted in their high selectivity. The structure-activity
      relationship and signaling pathways were also discussed. 

PMID- 27039887
TI  - Roles of the tyrosine isomers meta-tyrosine and ortho-tyrosine in oxidative
      stress.
AB  - The damage to cellular components by reactive oxygen species, termed oxidative
      stress, both increases with age and likely contributes to age-related diseases
      including Alzheimer's disease, atherosclerosis, diabetes, and cataract formation.
      In the setting of oxidative stress, hydroxyl radicals can oxidize the benzyl ring
      of the amino acid phenylalanine, which then produces the abnormal tyrosine
      isomers meta-tyrosine or ortho-tyrosine. While elevations in m-tyrosine and o
      tyrosine concentrations have been used as a biological marker of oxidative
      stress, there is emerging evidence from bacterial, plant, and mammalian studies
      demonstrating that these isomers, particularly m-tyrosine, directly produce
      adverse effects to cells and tissues. These new findings suggest that the
      abnormal tyrosine isomers could in fact represent mediators of the effects of
      oxidative stress. Consequently the accumulation of m- and o-tyrosine may disrupt
      cellular homeostasis and contribute to disease pathogenesis, and as result,
      effective defenses against oxidative stress can encompass not only the
      elimination of reactive oxygen species but also the metabolism and ultimately the
      removal of the abnormal tyrosine isomers from the cellular amino acid pool.
      Future research in this area is needed to clarify the biologic mechanisms by
      which the tyrosine isomers damage cells and disrupt the function of tissues and
      organs and to identify the metabolic pathways involved in removing the
      accumulated isomers after exposure to oxidative stress. 

PMID- 27039889
TI  - Curcumin directly inhibits the transport activity of GLUT1.
AB  - Curcumin, a major ingredient in turmeric, has a long history of medicinal
      applications in a wide array of maladies including treatment for diabetes and
      cancer. Seemingly counterintuitive to the documented hypoglycemic effects of
      curcumin, however, a recent report indicates that curcumin directly inhibits
      glucose uptake in adipocytes. The major glucose transporter in adipocytes is
      GLUT4. Therefore, this study investigates the effects of curcumin in cell lines
      where the major transporter is GLUT1. We report that curcumin has an immediate
      inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum
      inhibition of 80% achieved at 75 MUM curcumin. Curcumin also blocks activation of
      glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine
      oxide. Inhibition does not increase with exposure time and the inhibitory effects
      reverse within an hour. Inhibition does not appear to involve a reaction between
      curcumin and the thiol side chain of a cysteine residue since neither prior
      treatment of cells with iodoacetamide nor curcumin with cysteine alters
      curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of
      2DG transport by about half with little effect on the Km. The inhibitory effects
      of curcumin are not additive to the effects of cytochalasin B and 75 MUM curcumin
      actually reduces specific cytochalasin B binding by 80%. Taken together, the data
      suggest that curcumin binds directly to GLUT1 at a site that overlaps with the
      cytochalasin B binding site and thereby inhibits glucose transport. A direct
      inhibition of GLUT proteins in intestinal epithelial cells would likely reduce
      absorption of dietary glucose and contribute to a hypoglycemic effect of
      curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that
      overexpress GLUT1 and be another possible mechanism for the documented anticancer
      effects of curcumin. 

PMID- 27039890
TI  - Fibrin(ogen)olytic and antiplatelet activities of a subtilisin-like protease from
      Solanum tuberosum (StSBTc-3).
AB  - Plant serine proteases have been widely used in food science and technology as
      well as in medicine. In this sense, several plant serine proteases have been
      proposed as potential anti-coagulants and anti-platelet agents. Previously, we
      have reported the purification and identification of a plant serine protease from
      Solanum tuberosum leaves. This potato enzyme, named as StSBTc-3, has a molecular
      weight of 72 kDa and it was characterized as a subtilisin like protease. In this
      work we determine and characterize the biochemical and medicinal properties of
      StSBTc-3. Results obtained show that, like the reported to other plant serine
      proteases, StSBTc-3 is able to degrade all chains of human fibrinogen and to
      produces fibrin clot lysis in a dose dependent manner. The enzyme efficiently
      hydrolyzes beta subunit followed by partially hydrolyzed alpha and gamma subunits
      of human fibrinogen. Assays performed to determine StSBTc-3 substrate specificity
      using oxidized insulin beta-chain as substrate, show seven cleavage sites: Asn3
      Gln4; Cys7-Gly8; Glu13-Ala14; Leu15-Tyr16; Tyr16-Leu17; Arg22-Gly23 and Phe25
      Tyr26, all of them were previously reported for other serine proteases with
      fibrinogenolytic activity. The maximum StSBTc-3 fibrinogenolytic activity was
      determined at pH 8.0 and at 37 C. Additionally, we demonstrate that StSBTc-3 is
      able to inhibit platelet aggregation and is unable to exert cytotoxic activity on
      human erythrocytes in vitro at all concentrations assayed. These results suggest
      that StSBTc-3 could be evaluated as a new agent to be used in the treatment of
      thromboembolic disorders such as strokes, pulmonary embolism and deep vein
      thrombosis. 

PMID- 27039891
TI  - 1-Acetyl-3-[(3R)-hydroxyfatty acyl]glycerols: Lipid Compounds from Euphrasia
      rostkoviana Hayne and E. tetraquetra (Breb.) Arrond.
AB  - Five homologous acetylated acylglycerols of 3-hydroxyfatty acids (chain lengths
      C(14) - C(18)), named euphrasianins A - E, were characterized for the first time
      in Euphrasia rostkoviana Hayne (Orobanchaceae) by gas chromatography/mass
      spectrometry (GC/MS) and high-performance liquid chromatography/atmospheric
      pressure chemical ionization-mass spectrometry (HPLC/APCI-MS(n) ). In addition to
      mass spectrometric data, structures of euphrasianins were verified via a three
      step total synthesis of one representative homologue (euphrasianin A). The
      structure of the latter was confirmed by 1D- and 2D-NMR experiments as well as
      high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). The
      absolute configuration of the 3-hydroxyfatty acid moiety at C(3) was found to be
      R in the natural euphrasianins, which was determined by alkaline hydrolysis and
      methylation of a purified fraction, followed by chiral GC analysis. Furthermore,
      in extracts of Euphrasia tetraquetra (Breb.) Arrond. euphrasianins C and E were
      detected exclusively, indicating that this subclass of lipid constituents is
      possibly valuable for fingerprinting methods. 

PMID- 27039892
TI  - Comparison of nocturia response to desmopressin treatment in elderly men with and
      without nocturnal polyuria in real-life practice.
AB  - OBJECTIVES: To evaluate the safety and efficacy of low-dose desmopressin in
      elderly men with and without nocturnal polyuria (NP) in real-life practice.
      METHODS: Patients with lower urinary tract symptoms (LUTS)/ benign prostate
      hyperplasia (BPH) who were? 65 years old with refractory nocturia were enrolled
      in this study. We retrospectively analysed elderly men treated with adding
      desmopressin to current medications for nocturia according to category of the
      baseline nocturnal urine volume. The 48-h frequency volume chart (FVC),
      International Prostate Symptom Score (IPSS) and quality of life (QoL) were
      initially assessed and re-evaluated 12 weeks later. Serum sodium level was
      checked 1 week, 4 weeks, and 12 weeks after initiation of desmopressin therapy or
      suspected hyponatremia event. The mean change in numbers of nocturnal voids was
      evaluated for efficacy of treatment. RESULTS: A total of 136 patients were
      included with 55 in non-NP group and 81 in NP group. Hypertension was more common
      in NP group in regard of comorbidities. During treatment period, there were
      significant reductions of nocturnal voids from 4.22 +/- 1.38 to 2.31 +/- 0.98 (p
      < 0.001) in non-NP group and from 4.52 +/- 1.23 to 2.07 +/- 0.89 (p < 0.001) in
      NP group. The reduction in nocturnal voids was more significant in NP group (2.44
      +/- 1.15 vs. 1.91 +/- 1.48, p = 0.003). The mean decrease in serum sodium levels
      were 3.89 +/- 1.22 mmol/l (p < 0.001) in non-NP group and 4.69 +/- 3.5 mmol/l (p
      < 0.001) in NP group at the extreme value. CONCLUSIONS: Long-term treatment with
      low-dose desmopressin is safe and effective for nocturia with or without NP in
      elderly patients with LUTS/BPH during real-life practice. Patients should be well
      informed about the disease and are closely followed.

PMID- 27039893
TI  - Overconfidence, Incentives and Digit Ratio.
AB  - This paper contributes to a better understanding of the biological underpinnings
      of overconfidence by analyzing performance predictions in the Cognitive
      Reflection Test with and without monetary incentives. In line with the existing
      literature we find that the participants are too optimistic about their
      performance on average; incentives lead to higher performance; and males score
      higher than females on this particular task. The novelty of this paper is an
      analysis of the relation between participants' performance prediction accuracy
      and their second to fourth digit ratio. It has been reported that the digit ratio
      is a negatively correlated bio-marker of prenatal testosterone exposure. In the
      un-incentivized treatment, we find that males with low digit ratios, on average,
      are significantly more overconfident about their performance. In the incentivized
      treatment, however, we observe that males with low digit ratios, on average, are
      less overconfident about their performance. These effects are not observed in
      females. We discuss how these findings fit into the literature on testosterone
      and decision making and how they might help to explain seemingly opposing
      evidence. 

PMID- 27039894
TI  - Light emitting diode mediated photobiomodulation therapy improves orthodontic
      tooth movement and miniscrew stability: A randomized controlled clinical trial.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effects of
      light-emitting diode-mediated-photobiomodulation therapy (LPT) on the stability
      of miniscrews, rate of orthodontic tooth movement, and interleukin-1beta levels
      in gingival and peri-implant crevicular fluid. MATERIALS AND METHODS: This study
      was a double blind, randomized placebo/control matched pairs clinical trial to
      test the efficacy of LPT. This split-mouth design study consisted of 20 patients
      (13 girls, 7 boys). The eligibility criteria included patients who had extraction
      of maxillary first premolars. Mini-screws were placed between maxillary first
      molars and second premolars on both sides as anchorage units. LPT was applied
      with an energy density of 20 mW/cm2 over a period of 21 successive days (20
      minutes per day) over the movement of canine teeth on the test side and using a
      pseudo application on the placebo side. The main outcome of this study was to
      assess effect of LPT on the rate of orthodontic tooth movement. The secondary
      outcomes were measuring stability of miniscrews and interleukin-1beta levels in
      gingival and peri-implant crevicular fluid after LPT. Randomization was
      accomplished with random LPT application side selection by coin toss.
      Measurements were made by blinding clinicians. Blinding of the patients was
      achieved using the same LPT device on both sides but irradiating only one side.
      For statistical comparison, paired samples t-test and one-way analysis of
      variance (ANOVA) were used at P < 0.05 level. RESULTS: Miniscrew stability was
      similar between control and LPT groups at baseline (T0) and the 1st month (T1).
      However, miniscrew stability was significantly increased in the LPT group in 2nd
      (T2) and 3rd (T3) months. Comparison of tooth movement during three different
      time intervals (T1-T0, T2-T1, and T3-T2) revealed that statistically
      significantly increased in every time intervals after LPT. No statistically
      significant change was detected in the IL-1beta levels between groups.
      CONCLUSION: LPT had the potential of accelerating orthodontic tooth movement and
      had a positive effect on miniscrew stability. Lasers Surg. Med. 48:936-943, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27039895
TI  - Differential expression of microRNAs in bovine papillomavirus type 1 transformed
      equine cells.
AB  - Bovine papillomavirus (BPV) types 1 and 2 play an important role in the
      pathogenesis of equine sarcoids (ES), the most common cutaneous tumour affecting
      horses. MicroRNAs (miRNAs), small non-coding RNAs that regulate essential
      biological and cellular processes, have been found dysregulated in a wide range
      of tumours. The aim of this study was to identify miRNAs associated with ES.
      Differential expression of miRNAs was assessed in control equine fibroblasts
      (EqPalFs) and EqPalFs transformed with the BPV-1 genome (S6-2 cells). Using a
      commercially available miRNA microarray, 492 mature miRNAs were interrogated. In
      total, 206 mature miRNAs were differentially expressed in EqPalFs compared with
      S6-2 cells. Aberrant expression of these miRNAs in S6-2 cells can be attributed
      to the presence of BPV-1 genomes. Furthermore, we confirm the presence of 124
      miRNAs previously computationally predicted in the horse. Our data supports the
      involvement of miRNAs in the pathogenesis of ES.

PMID- 27039896
TI  - Gossip Versus Punishment: The Efficiency of Reputation to Promote and Maintain
      Cooperation.
AB  - Prior theory suggests that reputation spreading (e.g., gossip) and punishment are
      two key mechanisms to promote cooperation in groups, but no behavioral research
      has yet examined their relative effectiveness and efficiency in promoting and
      maintaining cooperation. To examine these issues, we observed participants
      interacting in a four-round public goods game (PGG) with or without gossip and
      punishment options, and a subsequent two-round trust game (TG). We manipulated
      gossip as the option to send notes about other group members to these members'
      future partners, and punishment as the option to assign deduction points to
      reduce other group members' outcomes with a fee-to-fine ratio of 1:3. Findings
      revealed that in the four-round PGG, the option to gossip increased both
      cooperation and individual earnings, whereas the option to punish had no overall
      effect on cooperation (but a positive effect on cooperation in the last two
      rounds of the PGG) and significantly decreased individual earnings. Importantly,
      the initial option to gossip made people more trusting and trustworthy in the
      subsequent TG when gossip was no longer possible, compared to the no-gossip
      condition. Thus, we provide some initial evidence that gossip may be more
      effective and efficient than punishment to promote and maintain cooperation.

PMID- 27039897
TI  - Soil and river contamination patterns of chlordecone in a tropical volcanic
      catchment in the French West Indies (Guadeloupe).
AB  - The aim of this study was to identify primary flow paths involved in the
      chlordecone (CLD) river contamination and quantify the CLD fluxes to assess CLD
      pollution levels and duration according to a typical catchment of the banana
      cropping area in the French Indies (Guadeloupe): the Perou Catchment (12 km(2))
      characterized by heavy rainfall (5686 mm year(-1)). Three sub-catchments (SC1,
      SC2 and SC3) were studied during the hydrological year 2009-2010: a pedological
      survey combined with a spatialized hydrochemical approach was conducted. The
      average soil concentration is higher in the Perou Catchment (3400 MUg kg(-1))
      than in the entire banana cropping area in Guadeloupe (2100 MUg kg(-1)). The
      results showed that CLD stocks in soils vary largely among soil types and farming
      systems: the weakest stocks are located upstream in SC1 (5 kg ha(-1)), where a
      majority of the area is non-cultivated; medium stocks are located in Nitisols
      downstream in SC3 (9 kg ha(-1)); and the greatest stocks are observed in SC2 on
      Andosols (12 kg ha(-1)) characterized by large farms. The annual water balance
      and the hydro-chemical analysis revealed that the three sub-catchments exhibited
      different behaviors. Perou River contamination was high during low flows, which
      highlighted that contamination primarily originated from groundwater
      contributions. The results showed that only a small part of the catchment (SC2),
      contributing little to the water flow, comprises a major CLD contribution, which
      is in agreement with the highly contaminated andosol soils observed there.
      Another significant result considers that at least 50 years would be required to
      export the totality of the actual CLD soil stocks retained in the topsoil layer.
      The actual time for soil remediation will however be much longer considering (i)
      the necessary time for the chlordecone to percolate and be stored in the shallow
      aquifers and (ii) its travel time to reach the river. 

PMID- 27039898
TI  - Water soluble and insoluble components of urban PM2.5 and their cytotoxic effects
      on epithelial cells (A549) in vitro.
AB  - When PM2.5 enters human bodies, the water soluble (WS-PM2.5) and insoluble
      components (WIS-PM2.5) of PM2.5 would interact with cells and cause adverse
      effects. However, the knowledge about the individual toxicity contribution of
      these two components is limited. In this study, the physiochemical properties of
      PM2.5 were well characterized. The toxic effects of WS-PM2.5 and WIS-PM2.5, which
      include the cell viability, cell membrane damage, reactive oxygen species (ROS)
      generation and morphological changes, were examined with human lung epithelial
      A549 cells in vitro. The results indicated that WS-PM2.5 could induce the early
      response of ROS generation, multiplied mitochondria and multi-lamellar bodies in
      A549 cells, which might cause cell damage through oxidative stress. Meanwhile,
      WIS-PM2.5 was predominantly associated with the cell membrane disruption, which
      might lead to the cell damage through cell-particle interactions. Moreover, the
      synergistic cytotoxic effects of WS-PM2.5 and WIS-PM2.5 were observed at longer
      exposure time. These findings demonstrate the different cytotoxicity mechanisms
      of WS-PM2.5 and WIS-PM2.5, which suggest that not only the size and dosage of
      PM2.5 but also the solubility of PM2.5 should be taken into consideration when
      evaluating the toxicity of PM2.5. 

PMID- 27039900
TI  - A discussion on cell therapy in Manchester.

PMID- 27039899
TI  - MAL62 overexpression and NTH1 deletion enhance the freezing tolerance and
      fermentation capacity of the baker's yeast in lean dough.
AB  - BACKGROUND: Trehalose is related to several types of stress responses, especially
      freezing response in baker's yeast (Saccharomyces cerevisiae). It is desirable to
      manipulate trehalose-related genes to create yeast strains that better tolerate
      freezing-thaw stress with improved fermentation capacity, which are in high
      demand in the baking industry. RESULTS: The strain overexpressing MAL62 gene
      showed increased trehalose content and cell viability after prefermention
      freezing and long-term frozen. Deletion of NTH1 in combination of MAL62
      overexpression further strengthens freezing tolerance and improves the leavening
      ability after freezing-thaw stress. CONCLUSIONS: The mutants of the industrial
      baker's yeast with enhanced freezing tolerance and leavening ability in lean
      dough were developed by genetic engineering. These strains had excellent
      potential industrial applications.

PMID- 27039901
TI  - Adipose tissue plasticity: how fat depots respond differently to
      pathophysiological cues.
AB  - White adipose tissue (WAT) has key metabolic and endocrine functions and plays a
      role in regulating energy homeostasis and insulin sensitivity. WAT is
      characterised by its capacity to adapt and expand in response to surplus energy
      through processes of adipocyte hypertrophy and/or recruitment and proliferation
      of precursor cells in combination with vascular and extracellular matrix
      remodelling. However, in the context of sustained obesity, WAT undergoes fibro
      inflammation, which compromises its functionality, contributing to increased risk
      of type 2 diabetes and cardiovascular diseases. Conversely, brown adipose tissue
      (BAT) and browning of WAT represent potential therapeutic approaches, since
      dysfunctional white adipocyte-induced lipid overspill can be halted by
      BAT/browning-mediated oxidative anti-lipotoxic effects. Better understanding of
      the cellular and molecular pathophysiological mechanisms regulating adipocyte
      size, number and depot-dependent expansion has become a focus of interest over
      recent decades. Here, we summarise the mechanisms contributing to adipose tissue
      (AT) plasticity and function including characteristics and cellular complexity of
      the various adipose depots and we discuss recent insights into AT origins,
      identification of adipose precursors, pathophysiological regulation of
      adipogenesis and its relation to WAT/BAT expandability in obesity and its
      associated comorbidities.

PMID- 27039902
TI  - Hypoxia reduces ER-to-Golgi protein trafficking and increases cell death by
      inhibiting the adaptive unfolded protein response in mouse beta cells.
AB  - AIMS/HYPOTHESIS: Hypoxia may contribute to beta cell failure in type 2 diabetes
      and islet transplantation. The adaptive unfolded protein response (UPR) is
      required for endoplasmic reticulum (ER) homeostasis. Here we investigated whether
      or not hypoxia regulates the UPR in beta cells and the role the adaptive UPR
      plays during hypoxic stress. METHODS: Mouse islets and MIN6 cells were exposed to
      various oxygen (O2) tensions. DNA-damage inducible transcript 3 (DDIT3), hypoxia
      inducible transcription factor (HIF)1alpha and HSPA5 were knocked down using
      small interfering (si)RNA; Hspa5 was also overexpressed. db/db mice were used.
      RESULTS: Hypoxia-response genes were upregulated in vivo in the islets of
      diabetic, but not prediabetic, db/db mice. In isolated mouse islets and MIN6
      cells, O2 deprivation (1-5% vs 20%; 4-24 h) markedly reduced the expression of
      adaptive UPR genes, including Hspa5, Hsp90b1, Fkbp11 and spliced Xbp1. Coatomer
      protein complex genes (Copa, Cope, Copg [also known as Copg1], Copz1 and Copz2)
      and ER-to-Golgi protein trafficking were also reduced, whereas apoptotic genes
      (Ddit3, Atf3 and Trb3 [also known as Trib3]), c-Jun N-terminal kinase (JNK)
      phosphorylation and cell death were increased. Inhibition of JNK, but not
      HIF1alpha, restored adaptive UPR gene expression and ER-to-Golgi protein
      trafficking while protecting against apoptotic genes and cell death following
      hypoxia. DDIT3 knockdown delayed the loss of the adaptive UPR and partially
      protected against hypoxia-induced cell death. The latter response was prevented
      by HSPA5 knockdown. Finally, Hspa5 overexpression significantly protected against
      hypoxia-induced cell death. CONCLUSIONS/INTERPRETATION: Hypoxia inhibits the
      adaptive UPR in beta cells via JNK and DDIT3 activation, but independently of
      HIF1alpha. Downregulation of the adaptive UPR contributes to reduced ER-to-Golgi
      protein trafficking and increased beta cell death during hypoxic stress.

PMID- 27039903
TI  - New Genetic Approaches to AD: Lessons from APOE-TOMM40 Phylogenetics.
AB  - Clinical trials for Alzheimer's disease are now focusing on the earliest stages
      of the disease with the goal of delaying dementia onset. There is great utility
      in using genetic variants to identify individuals at high age-dependent risk when
      the goal is to begin treatment before the development of any cognitive symptoms.
      Genetic variants identified through large-scale genome-wide association studies
      have not substantially improved the accuracy provided by APOE genotype to
      identify people at high risk of late-onset Alzheimer's disease (LOAD). We
      describe novel approaches, focused on molecular phylogenetics, to finding genetic
      variants that predict age at LOAD onset with sufficient accuracy and precision to
      be useful. We highlight the discovery of a polymorphism in TOMM40 that, in
      addition to APOE, may improve risk prediction and review how TOMM40 genetic
      variants may impact the develop of LOAD independently from APOE. The analysis
      methods described in this review may be useful for other genetically complex
      human diseases.

PMID- 27039905
TI  - Association of serum chloride level with mortality and cardiovascular events in
      chronic kidney disease: the CKD-ROUTE study.
AB  - BACKGROUND: Electrolyte abnormalities, particularly dysnatremia, are independent
      predictors of adverse outcome in individuals with and without renal failure.
      However, the association of serum chloride level (Cl-) with mortality or risk of
      cardiovascular (CV) events in chronic kidney disease (CKD) remains unclear.
      METHODS: This prospective cohort study included 923 pre-dialysis CKD G2-G5
      patients among the participants of the CKD Research of Outcomes in Treatment and
      Epidemiology (CKD-ROUTE) study, who newly visited 16 nephrology centers. The
      primary outcome was a composite of overall death and CV events, and the secondary
      outcome was overall death. Data were analyzed using the Cox hazards model with
      adjustment for potential confounders. RESULTS: Median Cl- was 106.0 mEq/L at
      enrollment [quartile (Q) 1: <=103.9, n =  207; Q2: 104.0-105.9, n =  207; Q3:
      106.0-108.0, n =  289; Q4: >=108.1, n = 220]. During a median follow-up of 33
      months, there were 98 CV events, 66 deaths, and 154 composite outcomes. The
      hazard ratio (HR) for the composite outcome was higher for Q1 than Q3 [HR 1.72;
      95 % confidence interval (CI) 1.08-2.72; P =  0.022]. As a continuous variable in
      a subset of patients whose Cl- was <=106.0 mEq/L, higher Cl- was associated with
      lower risk of the composite outcome (HR 0.93; 95 % CI 0.87-0.99; P = 0.023). HR
      for all-cause mortality was also higher for Q1 than Q3 (HR 2.48; 95 % CI 1.22
      5.03; P =  0.012). CONCLUSION: Low Cl- was associated with increased mortality
      and risk of CV events in pre-dialysis CKD patients. Cl- may be an additional
      prognostic indicator in CKD.

PMID- 27039906
TI  - Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell
      activation via alphav integrin interaction.
AB  - BACKGROUND: Periostin is a matricellular protein that serves as a ligand for
      integrins and is required for tissue remodeling and fibrosis. We investigated the
      role of periostin in hepatic fibrosis and the mechanisms involved. METHODS:
      Primary hepatic stellate cells (HSCs) and the HSC-immortalized cell line LX2 were
      used to study the profibrotic property of periostin and the interaction of
      periostin with integrins. Wild-type and periostin-deficient (periostin-/-) mice
      were subjected to two distinct models of liver fibrosis induced by hepatotoxic
      (carbon tetrachloride or thioacetamide) or cholestatic (3.5-diethoxycarbonyl-1.4
      dihydrocollidine) injury. RESULTS: Periostin expression in HSCs and LX2 cells
      increased in association with their activation. Gene silencing of periostin
      resulted in a significant reduction in the levels of profibrotic markers. In
      addition to enhanced cell migration in response to periostin, LX2 cells incubated
      on periostin showed significant induction of alpha-smooth muscle actin and
      collagen, indicating a profibrotic property. An antibody targeting alphavbeta5
      and alphavbeta3 integrins suppressed cell attachment to periostin by 60 and 30 %
      respectively, whereas anti-alpha5beta1 antibody had no effect. Consistently,
      alphav integrin-silenced LX2 cells exhibited decreased attachment to periostin,
      with a significant reduction in the levels of profibrotic markers. Moreover,
      these profibrotic effects of periostin were observed in the mouse models. In
      contrast to extensive collagen deposition in wild-type mice, periostin-/- mice
      developed less noticeable hepatic fibrosis induced by hepatotoxic and cholestatic
      liver injury. Accordingly, the profibrotic markers were significantly reduced in
      periostin-/- mice. CONCLUSION: Periostin exerts potent profibrotic activity
      mediated by alphav integrin, suggesting the periostin-alphav integrin axis as a
      novel therapeutic target for hepatic fibrosis.

PMID- 27039907
TI  - Louis Nico Marie Duysens (March 15, 1921-September 8, 2015): a leading
      biophysicist of the 20th century.
AB  - Louis Nico Marie (L. N. M.) Duijsens (Duysens) was one of the giants in the
      biophysics of photosynthesis. His PhD thesis "Transfer of Excitation Energy in
      Photosynthesis" (Duysens, 1952) is a classic; he introduced light-induced
      absorption difference spectroscopy to photosynthesis research and proved the
      existence of reaction centers, introducing advanced methods from physics to
      understand biological processes. Further, it is his 1959-1961 seminal work, with
      Jan Amesz, that provided evidence for the existence of the series scheme for the
      two light reactions in oxygenic photosynthesis. In one word, he was one of the
      master biophysicists of the 20th century-who provided direct measurements on many
      key intermediates, and made us understand the intricacies of photosynthesis with
      a simplicity that no one else ever did. We present here our personal perspective
      of the scientist that Lou Duysens was. For an earlier perspective, see van
      Grondelle and van Gorkom (Photosynth Res 120: 3-7, 2014). 

PMID- 27039908
TI  - [Not Available].

PMID- 27039909
TI  - [Rheumatism in elderly patients].

PMID- 27039910
TI  - [Prophylaxis and treatment of infections in elderly patients with rheumatism].
AB  - In general, the risk of serious infections increases with age, mainly explained
      by immunosenescence and accumulation of comorbidities. Those patients with
      rheumatoid arthritis who are of advanced age and require treatment with
      immunosuppressive agents are at particular risk to develop an infectious disease.
      Actual requirement and kind of treatment on the one hand, and risk of infection
      on the other hand, have to be considered carefully for each patient. For example,
      in high-risk patients, it is important to use glucocorticoids in a minimal way,
      i.e. in low doses and as short as possible. Vaccination, especially against
      influenza and pneumococci, plays an essential role in preventing infectious
      diseases, particularly in the elderly. Nevertheless, in cases of suspected
      bacterial infection, empiric antibiotic therapy should be started promptly. Due
      to the burden of drugs taken by patients of advanced age, the benefits and
      possible side effects as well as potential drug interactions have to be carefully
      considered. In summary, drug treatment of the elderly requires bearing in mind
      the complete health status of the individual patient. 

PMID- 27039911
TI  - [Recommendations on the use of rituximab for ANCA-associated vasculitis].
AB  - Rituximab (Rtx) has been approved in Germany since April 2013 for treatment of
      granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). This
      therapy can be used in severe manifestations of these diseases and in relapses.
      It is administered as infusions of 375 mg rituximab per m(2) every 4 weeks after
      high dose intravenous prednisolone for 3 days and continued parallel to
      concomitant oral prednisolone therapy. Recommendations for the indications and
      use for antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV)
      are described in addition to previous publications on recommendations for
      rheumatoid arthritis. 

PMID- 27039914
TI  - Audit of Pediatric Transfusion Practices in a Tertiary Care Hospital:
      Correspondence.

PMID- 27039915
TI  - Audit of Pediatric Transfusion Practices in a Tertiary Care Hospital: Expert's
      Opinion.

PMID- 27039916
TI  - Ovarian Edema (A Pseudotumor) - Gynaecologist's Dilemma.

PMID- 27039917
TI  - Erratum to: Biological evaluation of the toxicity and the cell cycle interruption
      by some benzimidazole derivatives.

PMID- 27039918
TI  - The Role of Stromal Components in Pancreatic Cancer Progression.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers,
      and is known for its extremely poor prognosis. Because of the location and
      composition of the organ, early symptoms cannot be visualized as easily as in
      other solid tumors. In the past decades, researchers have been mostly working on
      the genetic and epigenetic alterations of the cancer cells themselves, and
      therapies on pancreatic cancer cells alone have failed to significantly improve
      patient outcome. With the identification of abundant tumor stromal responses, the
      focus of pancreatic cancer research has begun to change. Increasing evidence has
      proved that the tumor stroma, especially the cell components (such as pancreatic
      stellate cells, tumor-associated macrophages, mast cells etc.) plays a key role
      in the development of PDAC. In this review, we discuss the interactions between
      cancer cells and several important cell components of the tumor stroma, as well
      their role in tumor growth, migration, invasion, angiogenesis and immune
      recognition.

PMID- 27039919
TI  - 4-Anilinoquinazoline Derivatives with Epidermal Growth Factor Receptor Inhibitor
      Activity.
AB  - 4-Anilinoquinazoline derivatives possess high anti-cancer activities. Many of
      them are highly selective tyrosine kinase inhibitors (TKI), particularly against
      epidermal growth factor receptor (EGFR). EGFRs are overexpressed or mutated in
      most carcinomas and are required for tumor progression. The efficacy of EGFR
      targeted anti-tumor drugs is impaired by drug-induced acquired resistance.
      Therefore, there is urgency to find better anti-cancer agents with novel effects
      on EGFR. 4-Anilinoquinazolines are small molecule EGFR inhibitors that have been
      synthesized and assessed for their anti-tumor bioactivity. In this paper, we
      review the 4-anilinoquinazoline derivatives with EGFR inhibitor activity reported
      in recent years.

PMID- 27039920
TI  - In Vitro Anticancer Effects of Two New Potent Hydrazide Compounds on Leukemic
      Cells.
AB  - BACKGROUND: Chronic myeloid leukemia (CML), also recognized as chronic
      myelogenous leukemia, is initiated in some types of blood-forming cells of the
      bone marrow. The therapeutic approach to CML is usually chemotherapy; however,
      severe side effects and complications are major problems in the clinical
      research. Thus, recent efforts have focused on the search for compounds affecting
      apoptosis in this type of cancer. OBJECTIVE: In this study, in vitro anticancer
      activity of two compounds (A and B) consisting of a hydrazide backbone with nitro
      thiophen and furan substituents was assessed against K562 cell line displaying
      certain levels of sensitivity to pro-apoptotic compounds. METHODS: The anticancer
      activity was assessed using MTT assay, flowcytometry, annexin-V and Western blot
      analysis. RESULTS: Compounds A and B were both active and revealed a remarkable
      in vitro cytotoxic effect showing IC50 values of 0.09 and 0.07 MUM, respectively,
      after 72 h of treatment. A significant increase in annexin-V/PI staining, sub-G1
      population and Bax/Bcl-2 ratio revealed the apoptotic cell death of compounds A-
      and B-treated K562 cells. CONCLUSION: The results presented here could be used as
      a first step for the development of powerful chemotherapeutic agents to treat
      leukemia.

PMID- 27039921
TI  - Autophagy Inhibits Apoptosis Induced by agrocybe aegerita Lectin in
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Lectins are carbohydrate-binding proteins that exhibit remarkable
      antitumor activities by inducing apoptotic or autophagic cell death. However, the
      relationship between apoptosis and autophagy induced by lectins has rarely been
      reported. Agrocybe aegerita lectin (AAL), a lectin isolated from the fungus
      Agrocybe aegerita, exerts antitumor activity through apoptosis. OBJECTIVE: To
      study the relationship between the autophagy and apoptosis induced by AAL in
      hepatocellular carcinoma (HCC) cells, and then to promote the antitumor effect of
      AAL. METHOD: AAL was evaluateted using the CCK-8 kit and the trypan blue assay.
      Cell autophagy was studied using western blotting, acridine orange straining,
      transmission electron microscopy, and transient transfection of pEGFPLC3
      plasmids. We also evaluated AAL-induced autophagy in Caenorhabditis elegans.
      Apoptosis was studied using flow cytometry. We also identified the antitumor
      effects of co-treatment of AAL with chloroquine (CQ) in vitro and in vivo.
      RESULTS: AAL-treated cell lines showed accumulation of microtubule-associated
      protein light chain 3 II (LC3-II), formation of EGFP-LC3 puncta and acidic
      autophagic vacuoles (AVOs), and the induction of autophagosomes. Inhibition of
      autophagy could enhance apoptosis induced by AAL in HCC cells. Furthermore, co
      therapy (AAL and chloroquine) promote antitumor effect of AAL in a murine in situ
      HCC model. CONCLUSION: Our findings suggest that inhibition of autophagy exerts a
      synergistic effect on the antitumor activity of AAL and may be a helpful strategy
      for reducing the dosage of lectin used in antitumor therapy. The autophagy
      inhibitor may be a synergist of certain antitumor drugs that can induce both
      apoptosis and autophagy.

PMID- 27039922
TI  - Brain-metastatic Breast Cancer: Clinical Considerations and Pharmacological
      Approaches.
AB  - Despite constant advances on breast cancer knowledge, the metastatic disease
      resulting from the spreading of this disease is still a challenge. This scenario
      is particularly critical in the more aggressive subtypes, as HER2-amplified and
      triple negative breast cancers, when often occurs the invasion of central nervous
      system (CNS) structures. In this situation, the survival of patients is
      drastically reduced, and the number of sequels and functional impairment is huge
      due to the small therapeutic arsenal available. In this context, it is necessary
      to understand the mechanisms involved in the process of metastasis of breast
      cancer to CNS, and how this process affects anatomically important structures for
      its functioning. This review aims to point out some mechanisms enrolled in the
      spread of breast cancer to CNS, discuss the clinical impact of such
      metastatisation and address the critical aspects related to the treatment of this
      condition.

PMID- 27039923
TI  - Anticancer Drug Combinations, How Far We can Go Through?
AB  - Many clinical cancer therapies are less effective by using one anticancer drug
      only due to refractory properties of cancer pathogenesis and drug resistance
      property in advanced cancer patients. A general consensus among clinicians is
      that anticancer drug cocktail might better control cancer progresses and
      metastasis than single drug therapeutics in clinical trials. Despite great
      popularity, the anticancer drug combination dogma has not been established. The
      complexity of drug combination dogma discovery is more than we can expect now.
      This article speculates possible routes we can undertake in this matter. The
      background knowledge of drug combination therapy presently practiced and possible
      future landscapes and drawbacks of cancer drug combinative therapies are
      highlighted.

PMID- 27039924
TI  - Synthesis of Icaritin and beta-anhydroicaritin Mannich Base Derivatives and Their
      Cytotoxic Activities on Three Human Cancer Cell Lines.
AB  - BACKGROUND: Prenyl flavonoid icaritin (1) and beta-anhydroicaritin (2) are two
      natural products with important biological and pharmacological effects. such as
      antiosteoporosis, estrogen regulation and antitumor properties. OBJECTIVE: The
      present study investigates the synthesis and cytotoxic activities on three Human
      cancer cell lines (Hela, HCC1954 and SK-OV-3) of icaritin and beta
      anhydroicaritin Mannich base derivatives in vitro models. METHOD: Preylated
      flavonoid icaritin (1) upon treatment with formic acid under microwave assistance
      gave another natural product beta-anhydroicaritin (2) in good yield (89%). Based
      on Mannich reaction of 1 or 2 with various secondary amines and formaldehyde, two
      series eighteen new 6-aminomethylated flavonoids Mannich base derivatives 3-11
      and 12-20 were synthesized. Their cytotoxic potential against three human cancer
      cell lines (Hela, HCC1954 and SK-OV-3) were evaluated by the standard MTT method
      with cis-Platin and Paclitaxel as positive control. RESULTS: Our research showed
      that most of these flavonoid Mannich base derivatives displayed equal or higher
      (lower IC50 values) cytotoxic activities than the positive control cis-Platin.
      Some compounds possess the IC50 value below 10uM. Compounds 6
      (diisopropylamino)methyl- and 6-morpholinylmethyl substituted beta
      anhydroicaritin (15 and 19) showed selective cytotoxicity against HCC1954 cells
      (IC50 12.688 uM) and Hela cells (IC50 6.543 uM) respectively. CONCLUSION: Our
      finding most of icaritin and beta-anhydroicaritin Mannich base derivatives
      possessing moderate to potent cytotoxicity against these three cancer cells
      (Hela, HCC1954 and SK-OV-3). Compound 15 and 19 showed selective cytotoxicity
      against HCC1954 cells and Hela cells respectively, they are potential and
      selective anticancer agent and worthy of further development.

PMID- 27039925
TI  - Differential Cytotoxicity, Cellular Uptake, Apoptosis and Inhibition of BRCA1
      Expression of BRCA1-Defective and Sporadic Breast Cancer Cells Induced by an
      Anticancer Ruthenium(II)-Arene Compound, RAPTA-EA1.
AB  - BACKGROUND: The RAPTA-EA1 complex [ruthenium(II)-arene 1,3,5-triaza-7
      phosphaadamantane (pta) complex with an arene-tethered ethacrynic acid ligand]
      has been reported to overcome drug resistance that developed due to the current
      use of platinum-based treatments. However, the exact mechanism of action of RAPTA
      EA1 remains largely unexplored and unknown. OBJECTIVE: Here we have further
      studied the effect of RAPTA-EA1 on BRCA1-defective HCC1937 breast cancer cells
      and compared its effects on BRCA1-competent MCF-7 breast cancer cells. METHOD:
      HCC1937 and MCF-7 breast cancer cells were treated with the RAPTA-EA1 complex.
      The cytotoxicity of ruthenium-induced cells was evaluated by a MTT assay.
      Cellular uptake of ruthenium was determined by ICP-MS. Cell cycle and apoptosis
      were assessed using a flow cytometer. Expression of BRCA1 mRNA and its encoded
      protein was quantitated by a real-time RT-PCR and Western blotting. RESULTS:
      Differences in cytotoxicity were correlated with the differential accumulations
      of ruthenium and the induction of apoptosis. The ruthenium complex caused
      dramatically more damage to the BRCA1 gene in the BRCA1-defective HCC1937 cells
      than to the BRCA1-competent MCF-7 cells. It decreased the expression of BRCA1
      mRNA in the BRCA1-competent cells, while in contrast, its expression increased in
      the BRCA1-defective cells. However, the expression of the BRCA1 protein was
      significantly reduced in both types of breast cancer cells. CONCLUSION: The
      results presented here have demonstrated a differential cellular response for the
      BRCA1-defective and BRCA1-competent breast cancer cells to RAPTA-EA1. These
      findings have provided more insight into the actions and development of the
      ruthenium-based compounds for use for the treatment of breast cancer.

PMID- 27039926
TI  - Effects of Epirubicin and Cisplatin Against 4T1 Breast Cancer Cells are Enhanced
      by Myrtucommulone-A.
AB  - BACKGROUND: The number of cancer cases around the world has increased according
      to the World Health Organization (WHO) reports, nearly 14 million new cases and
      8.2 million cancer associated mortalities have been reported in 2012.
      Chemotherapeutic resistance is a major problematic issue in the management of
      patients with breast tumor. OBJECTIVE: In this study, the apoptotic gene profile
      of 4T1 mouse breast cancer cells treated with MC-A in combination with cisplatin
      or epirubicin was evaluated to decipher the possible apoptotic molecular targets.
      METHODS: The effects of MC-A in combination with cisplatin (CIS) or epirubicin
      (EPI) on cytotoxicity, cell migration, wound healing, clonogenicity along with
      enhanced effect of these combinations on 84 apoptosis related genes were tested
      in 4T1 cancer cells. RESULTS: MC-A in combination with epirubicin or cisplatin
      robustly induced cytotoxicity in 4T1 cells in vitro. MC-A in combination with
      cisplatin or epirubicin showed significantly inhibition of cell migration
      compared to treatment with each agent alone. Genes involved in positive
      regulation of apoptosis, negative regulator of apoptosis, death-like,
      mitochondrial apoptotic signaling, induction of apoptosis through DR3 and DR4/5
      death receptors, and anti-apoptosis were highly affected in MC-A+cisplatin or MC
      A+epirubicin combinations compared to each agent only. CONCLUSIONS: In
      conclusion, the apoptotic response of 4T1 cancer cells to chemotherapeutic drugs
      occurs in different ways. MC-A in combination with these chemotherapeutic drugs
      could modulate the expression of genes involved in both extrinsic and intrinsic
      pathways of apoptosis, leading to higly effective apoptotic signalling in cancer
      treatment.

PMID- 27039927
TI  - Synthesis and in vitro Evaluation of the Anticancer Potential of New Aminoalkanol
      Derivatives of Xanthone.
AB  - A series of 15 derivatives of xanthone were synthesized and evaluated for the
      anticancer activity. The structure of the tested compounds was diversified to
      establish structureactivity relationships. The following evaluations were carried
      out: cytotoxicity-proliferation tests, apoptosis detection, expression of
      apoptosis and proliferation-related genes, expression and activity of gelatinases
      A and B, wound migration assays, and cell adhesion to MatrigelTMcoated plates.
      Four compounds (7, 12, 13 and 15) displayed direct cytotoxicity at micromolar
      concentrations toward the studied cell lines. They also significantly affected
      the expression of proliferationapoptosis markers, and 13 demonstrated as strong
      influence as alpha-mangostin, that served as a natural standard in our study.
      These four compounds also decreased the expression and activity of gelatinases,
      and inhibited the migration-motility potential of cancer cells. The influence of
      compounds 7 and 12 on MMPs mRNA levels even exceeded the activity of alpha
      mangostin and shRNA-mediated silencing; zymography revealed that 7, 13 and 15
      were as equally active as alpha-mangostin, despite their higher IC50 values. The
      highest activity to inhibit motility and migration of cancer cells was
      demonstrated by 7, 12, 15, and by alpha-mangostin; and this was almost equal to
      shRNA-mediated silencing. Structural features predetermining compound activity
      were: substitution at position C4 instead of C2, and presence of a chlorine atom
      and allyl moiety. These results indicate that synthesis of aminoalkanol
      derivatives of xanthone may lead to successful establishment of new potential
      anticancer chemicals.

PMID- 27039928
TI  - Treatment of Obstructive Sleep Apnea in Young and Middle-Aged Adults: Effects of
      Positive Airway Pressure and Compliance on Arterial Stiffness, Endothelial
      Function, and Cardiac Hemodynamics.
AB  - BACKGROUND: The cardiovascular effects of positive airway pressure (PAP) therapy
      in obstructive sleep apnea (OSA) patients are not clear because of confounding by
      comorbid conditions. METHODS AND RESULTS: Prospective interventional study of PAP
      therapy and withdrawal. Apnea Hypopnea Index (AHI; events/hour of sleep) was
      determined from polysomnography. Central aortic blood pressures (BPs), Aortic
      Augmentation Index (AAIx), and central (PWVc-f) and peripheral pulse wave (PWVc
      r) velocities were determined by applanation tonometry. Echocardiography and
      brachial artery reactivity testing were performed at baseline, after 4 and 12
      weeks of PAP therapy, and 1 week after PAP withdrawal. The 84 participants were
      mean (SD) 41.1 (7.6) years old and had 39.8 (24.5) AHI events/hour. After 4 weeks
      post-PAP initiation and sustained after 12 weeks, subjects experienced decreases
      in central systolic BP (P=0.008), diastolic BP, mean BP, AAIx, and PWVc-r, and
      brachial artery dilation (all P<0.001), as well as improvements in left
      ventricular diastolic function and systemic and pulmonary vascular resistance. In
      adjusted models, PAP use (hours/night) predicted reductions in diastolic BP
      (beta=-0.65 [SE, 0.32] mm Hg/hour; P=0.045), AAIx (beta=-0.53 [0.27] %/hour;
      P=0.049) and PWVc-r (beta=-0.13 [0.05] m.s(-1)/hour; P=0.007), and improved
      brachial artery flow-mediated dilation (beta=0.31 [0.14] %/hour use; P=0.015).
      After 1 week of PAP withdrawal, brachial diameter, diastolic BP, mean BP, AAIx,
      and heart rate increased (P<=0.05). CONCLUSIONS: PAP therapy reduces arterial
      tone and improves endothelial and diastolic function in young to middle-aged
      adults. This positive effect is observed after 4 weeks and depends on hours of
      use, but reverts quickly with PAP withdrawal. CLINICAL TRIAL REGISTRATION: URL:
      https://clinicaltrials.gov/. Unique identifier: NCT01317329.

PMID- 27039929
TI  - Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis
      in ApoE-/- Mice With Unilateral Renal Artery Stenosis.
AB  - BACKGROUND: Chronic unilateral renal artery stenosis (RAS) causes accelerated
      atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice, but effects of
      restoration of renal blood flow on aortic atherosclerosis are unknown. METHODS
      AND RESULTS: Male ApoE(-/-) mice underwent sham surgery (n=16) or had partial
      ligation of the right renal artery (n=41) with the ligature being removed 4 days
      later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days
      (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal
      blood flow, decreased plasma angiotensin II levels, a return of systolic blood
      pressure to baseline, and increased plasma levels of neutrophil gelatinase
      associated lipocalin. Chronic RAS resulted in increased lipid staining in the
      aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P<0.05) and descending
      thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8]; P<0.05), compared to sham
      surgery. There was an increased amount of aortic arch lipid staining in the D8LR
      group (22.7% [22.1, 32.7]), compared to sham-surgery, but less than observed with
      chronic RAS. Lipid staining in the aortic arch was not increased in the D4LR
      group, and lipid staining in the descending aorta was not increased in either the
      D8LR or D4LR groups. There was less macrophage expression in infrarenal aortic
      atheroma in the D4LR and D8LR groups compared to the chronic RAS group.
      CONCLUSIONS: Restoration of renal blood flow at either 4 or 8 days after
      unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid
      deposition, and atheroma inflammation.

PMID- 27039930
TI  - Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected
      Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the
      Released Mature Enzyme.
AB  - We have systematically validated the activity and inhibition of a HIV-1 protease
      (PR) variant bearing 17 mutations (PR(S17)), selected to represent high
      resistance by machine learning on genotype-phenotype data. Three of five
      mutations in PR(S17) correlating with major drug resistance, M46L, G48V, and
      V82S, and five of 11 natural variations differ from the mutations in two
      clinically derived extreme mutants, PR20 and PR22 bearing 19 and 22 mutations,
      respectively. PR(S17), which forms a stable dimer (<10 nM), is ~10- and 2-fold
      less efficient in processing the Gag polyprotein than the wild type and PR20,
      respectively, but maintains the same cleavage order. Isolation of a model
      precursor of PR(S17) flanked by the 56-amino acid transframe region (TFP-p6pol)
      at its N-terminus, which is impossible upon expression of an analogous PR20
      precursor, allowed systematic comparison of inhibition of TFP-p6pol-PR(S17) and
      mature PR(S17). Resistance of PR(S17) to eight protease inhibitors (PIs) relative
      to PR (Ki) increases by 1.5-5 orders of magnitude from 0.01 to 8.4 MUM.
      Amprenavir, darunavir, atazanavir, and lopinavir, the most effective of the eight
      PIs, inhibit precursor autoprocessing at the p6pol/PR site with IC50 values
      ranging from ~7.5 to 60 MUM. Thus, this process, crucial for stable dimer
      formation, shows inhibition ~200-800-fold weaker than that of the mature PR(S17).
      TFP/p6pol cleavage, which occurs faster, is inhibited even more weakly by all PIs
      except darunavir (IC50 = 15 MUM); amprenavir shows a 2-fold increase in IC50 (~15
      MUM), and atazanavir and lopinavir show increased IC50 values of >42 and >70 MUM,
      respectively.

PMID- 27039931
TI  - Deleterious Effect of p-Cresol on Human Colonic Epithelial Cells Prevented by
      Proanthocyanidin-Containing Polyphenol Extracts from Fruits and Proanthocyanidin
      Bacterial Metabolites.
AB  - The protective effect of proanthocyanidin-containing polyphenol extracts from
      apples, avocados, cranberries, grapes, or proanthocyanidin microbial metabolites
      was evaluated in colonic epithelial cells exposed to p-cresol, a deleterious
      compound produced by the colonic microbiota from l-tyrosine. In HT29 Glc(-/+)
      cells, p-cresol significantly increased LDH leakage and decreased ATP contents,
      whereas in Caco-2 cell monolayers, it significantly decreased the transepithelial
      electrical resistance and increased the paracellular transport of FITC-dextran.
      The alterations induced by p-cresol in HT29 Glc(-/+) cells were prevented by the
      extracts from cranberries and avocados, whereas they became worse by extracts
      from apples and grapes. The proanthocyanidin bacterial metabolites decreased LDH
      leakage, ameliorating cell viability without improving intracellular ATP. All of
      the polyphenol extracts and proanthocyanidin bacterial metabolites prevented the
      p-cresol-induced alterations of barrier function. These results suggest that
      proanthocyanidin-containing polyphenol extracts and proanthocyanidin metabolites
      likely contribute to the protection of the colonic mucosa against the deleterious
      effects of p-cresol. 

PMID- 27039932
TI  - Au@MnS@ZnS Core/Shell/Shell Nanoparticles for Magnetic Resonance Imaging and
      Enhanced Cancer Radiation Therapy.
AB  - Although conventional radiotherapy (RT) has been widely used in the clinic to
      treat cancer, it often has limited therapeutic outcomes and severe toxic effects.
      There is still a need to develop theranostic agents with both imaging and RT
      enhancing functions to improve the accuracy and efficiency of RT. Herein we
      synthesize Au@MnS@ZnS core/shell/shell nanoparticles with polyethylene glycol
      (PEG) functionalization, yielding Au@MnS@ZnS-PEG nanoparticles with great
      stability in different physiological solutions and no significant cytotoxicity.
      It is found that Au@MnS@ZnS-PEG nanoparticles can enhance the cancer cell killing
      efficiency induced by RT, as evidenced by multiple in vitro assays. Owing to the
      existence of paramagnetic Mn(2+) in the nanoparticle shell, our Au@MnS@ZnS-PEG
      can be used as a contrast agent for T1-weighted magnetic resonance (MR) imaging,
      which reveals the efficient accumulation and retention of nanoparticles in the
      tumors of mice after intravenous injection. Importantly, by exposing tumor
      bearing mice that were injected with Au@MnS@ZnS-PEG to X-ray irradiation, the
      tumor growth can be significantly inhibited. This result shows clearly improved
      therapeutic efficacy compared to RT alone. Furthermore, no obvious side effect of
      Au@MnS@ZnS-PEG is observed in the injected mice. Therefore, our work presents a
      new type of radiosensitizing agent, which is promising for the imaging-guided
      enhanced RT treatment of cancer. 

PMID- 27039940
TI  - Nutrition with Gastrostomy Feeding Tubes for Amyotrophic Lateral Sclerosis in
      Canada.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing
      degenerative motor neuron disease that results in significant muscle weakness.
      Defects in energy metabolism and difficulties in swallowing eventually lead to a
      reduction in body mass. Weight loss exacerbates symptoms and serves as an
      independent negative prognostic factor. Percutaneous endoscopic gastrostomy (PEG)
      is often inserted in patients with ALS to either supplement or replace oral
      feeding. However, the criteria for PEG placement and timing of insertion are
      important clinical decisions that have not been fully studied. Given the absence
      of guiding evidence, the aim of this project was to better understand how
      Canadian ALS clinics make decisions regarding gastrostomy feeding. METHODS: ALS
      clinical directors across Canada were asked if they had written guidelines for
      timing of PEG insertion and if not, what criteria they use to make this decision.
      Responses from 10 of 17 centres contacted were received. RESULTS: The approach to
      supplemental nutrition management in Canadian clinics varies in the absence of
      formal guidelines. Only one centre has a written set of centre-specific protocols
      in place. Most clinics considered some combination of respiratory decline, weight
      loss, dysphagia and/or patient readiness when reaching a decision. However, the
      absolute threshold and mechanism of measuring the individual criteria differed
      between clinics. CONCLUSIONS: Practices generally reflect international published
      recommendations but vary on the emphasis of specific criteria. Further research
      is required to determine the optimal timing and criteria to place gastrostomy
      feeding tubes in the ALS population.

PMID- 27039941
TI  - The Effect of a Full Bladder on Proportions of Diagnostic Ultrasound Studies in
      Children with Suspected Appendicitis.
AB  - OBJECTIVES: We examined the effect of a full bladder on proportions of diagnostic
      ultrasound (US) studies in children with suspected appendicitis. We also examined
      the effect of a full bladder on proportions of fully visualized ovaries on US in
      children with suspected appendicitis. METHODS: We conducted a retrospective
      health record review of children aged 2-17 years presenting to a tertiary
      pediatric emergency department (ED) with suspected appendicitis who had an
      ultrasound performed. We compared proportions of diagnostic US studies in
      children with full and sub-optimally filled bladders. We also compared
      proportions of ovarian visualization in females with full and sub-optimally
      filled bladders. RESULTS: 678 children were included in our final analysis. The
      proportion of diagnostic US studies did not vary significantly between groups
      with a full (132/283, 47%, 95% confidence interval [CI] 38%-56%) or sub-optimally
      filled bladder (205/395, 52%, 95% CI 47%-57%)(p=0.17). Rates of ovarian
      visualization were higher in females with a full bladder (196/205, 96%, 95% CI
      93%-99%) compared to those with a sub-optimally filled bladder (180/223, 81%, 95%
      CI 76%-86%) (p<0.01). CONCLUSIONS: Administrators and clinical decision makers
      should consider removing routine bladder filling practice from current pediatric
      appendicitis protocols in males and in pre-pubertal females where ovarian
      pathology is not suspected. Selective bladder filling prior to US should be
      performed in females when ovarian pathology is suspected.

PMID- 27039942
TI  - Dynamics of a surface-modified miniaturized SiN mechanical resonator via a
      nanometer-scale pore array.
AB  - We have fabricated porous miniaturized SiN resonators with various dimensions and
      studied their mechanical dynamics at their resonant modes. The surface
      modification of the resonators has been achieved by etching through a thin porous
      anodic aluminum oxide (AAO) mask, prepared by two-step anodization. Even though
      these porous resonators show well-defined Lorentzian line-shapes at their
      resonant modes, the corresponding fundamental flexural resonance frequencies are
      lower than those from typical non-porous resonators. The change in the resonance
      frequency is due to the presence of the pores on the surface, which reduces the
      effective tensile stress across the beam structure, as shown from both
      experimental measurements and the computational model. In addition, the observed
      quality factor reveals the level of dissipation originating from the surface
      modification. The principal dissipation mechanism is found to be gas damping in
      the free molecular flow regime. Based on the dissipation measurement, one can see
      an increase in the surface-to-mass ratio, which is responsible for the increased
      dissipation in the porous beam structure. The work presented here demonstrates
      simple integration of mechanical elements with a nanopatterning technique based
      on an AAO as well as the tuning of mechanics via surface modification at a small
      scale. Such a scheme could provide an additional degree of freedom in developing
      a mechanical sensing element with enhanced effective surface area. 

PMID- 27039943
TI  - Improvement of Glucose Metabolism in the Visual Cortex Accompanies Visual Field
      Recovery in a Patient with Hemianopia.
AB  - Damage to the visual cortex or the geniculostriatal pathways could cause
      homonymous visual field (VF) defects at the contralateral side of the lesion. In
      clinical practice, it is known that the VF defects are gradually recovered over
      months on the cases. We report a case with recovered homonymous hemianopia
      following an infarction in the visual cortex by positron emission tomography
      (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-flumazenil (FMZ). A 58-year
      old man experienced defect of left VF, and magnetic resonance imaging (MRI)
      revealed a localized infarction in the right occipital lobe. Goldmann VF
      perimetry revealed left homonymous hemianopia, but central VF was intact. Three
      months after the onset of infarction, we measured cerebral glucose metabolism
      with FDG and FMZ binding using PET. FMZ binding reflects the density of surviving
      neurons. Moreover, eight months after the onset, FDG-PET scan was performed.
      Goldmann VF perimetry was also performed at the same times of PET examinations.
      Decrease of cerebral glucose metabolism in the right anterior striate cortex was
      observed at three months after onset, while FMZ binding in the same area did not
      decrease in the patient. At eight months after onset, we observed recovery of VF
      and improvement of cerebral glucose metabolism in the anterior striate cortex. We
      presented change of cerebral glucose metabolism using PET accompanying
      improvement of VF. Evaluation of cerebral glucose metabolism and FMZ binding in
      the striate cortex is useful for estimating the prognosis of hemianopia caused by
      organic brain damage. 

PMID- 27039944
TI  - Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive
      Intracranial Immature Teratoma.
AB  - Immature teratoma (IMT) is the most frequent histological subtype of infantile
      intracranial teratoma, the most common congenital brain tumor. IMT contains
      incompletely differentiated components resembling fetal tissues. Infantile
      intracranial IMT has a dismal prognosis, because it is often inoperable due to
      its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to
      be effective in decreasing tumor volume and vascularity to facilitate surgical
      resection in other types of infantile brain tumors. However, only one recent case
      report described the effectiveness of neoadjuvant chemotherapy for infantile
      intracranial IMT in the literature, even though it is common entity with a poor
      prognosis in infants. Here, we describe the case of a 2-month-old male infant
      with a very large intracranial IMT. Maximal surgical resection was first
      attempted but was unsuccessful because of severe intraoperative hemorrhage.
      Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered
      with the aim of shrinking and devascularizing the tumor. After neoadjuvant
      chemotherapy, tumor size did not decrease, but intraoperative blood loss
      significantly decreased and near-total resection was achieved by the second and
      third surgery. The patient underwent adjuvant CARE chemotherapy and has been
      alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant
      chemotherapy does not decrease tumor volume of infantile intracranial IMT,
      surgical resection should be tried because chemotherapy can facilitate surgical
      resection and improve clinical outcome by reducing tumor vascularity. 

PMID- 27039946
TI  - Long-Term Outcomes of Mitral Valve Repair for Active Endocarditis.
AB  - BACKGROUND: The long-term outcomes of mitral valve (MV) repair for active
      infective endocarditis (AE) are not well known, so the present study examined
      results from >5 years. METHODS AND RESULTS: We retrospectively reviewed 43
      patients who underwent primary MV repair for AE at a single center between 1991
      and 2009. Patients' mean age was 50.9 years, and 39% were female. The mean follow
      up was 7.4 years, and 90.7% of the patients had serial echocardiographic studies
      over the years. We examined the data for mortality, mitral reoperation, and
      recurrent significant mitral regurgitation (MR). There were no early deaths but 6
      late deaths. Survival was 92.6+/-4.1% for 5 years, and 83.5+/-7.3% for 10 years.
      The respective 5- and 10-year rates of freedom from MV reoperation were 90.5+/
      4.5% and 86.6+/-5.8%, and for freedom from moderate or severe MR were 95.0+/-3.5
      and 86.1+/-6.7%. Recurrence of endocarditis was observed in 2 patients (4.7%).
      Most (86%) of the survivors were in New York Heart Association class I.
      CONCLUSIONS: MV repair for AE is durable and offers acceptable long-term outcomes
      with low rates of recurrence and reoperation. (Circ J 2016; 80: 1148-1152).

PMID- 27039947
TI  - Titanate nanotubes for reinforcement of a poly(ethylene oxide)/chitosan polymer
      matrix.
AB  - Soft polyethylene oxide (PEO)/chitosan mixtures, reinforced with hard titanate
      nanotubes (TiNTs) by co-precipitation from aqueous solution, have been used to
      produce compact coatings by the 'drop-cast' method, using water soluble PEO
      polymer and stable, aqueous colloidal solutions of TiNTs. The effects of the
      nanotube concentration and their length on the hardness and modulus of the
      prepared composite have been studied using nanoindentation and nanoscratch
      techniques. The uniformity of TiNT dispersion within the polymer matrix has been
      studied using transmission electron microscopy (TEM). A remarkable increase in
      hardness and reduced Young's modulus of the composites, compared to pure polymer
      blends, has been observed at a TiNT concentration of 25 wt %. The short (up to 30
      min) ultrasound treatment of aqueous solutions containing polymers and a
      colloidal TiNT mixture prior to drop casting has resulted in some improvements in
      both hardness and reduced Young's modulus of dry composite films, probably due to
      a better dispersion of ceramic nanotubes within the matrix. However, further
      (more than 1 h) treatment of the mixture with ultrasound resulted in a
      deterioration of the mechanical properties of the composite accompanied by a
      shortening of the nanotubes, as observed by the TEM. 

PMID- 27039948
TI  - Multifunctionalization of C70 at the two polar regions with a high
      regioselectivity via oxazolination and benzylation reactions.
AB  - C70 multiadducts with a novel 1,2,3,4,41,56,57,58-configuration were prepared via
      oxazolination and benzylation reactions. The structures of the adducts were
      determined by single crystal X-ray diffraction and spectral characterization. The
      compounds exhibit a high LUMO level, and result in a high open-circuit voltage in
      devices with P3HT. 

PMID- 27039949
TI  - Modeling the tyrosine-sugar interactions in supersonic expansions: glucopyranose
      phenol clusters.
AB  - Sugars are fundamental building blocks for living organisms and their interaction
      with proteins plays a central role in fundamental biological processes, such as
      energy storage and production, post-transductional modifications or immune
      response. Understanding those processes require deep knowledge of the forces that
      drive the interactions at the molecular level. Here we explore the interactions
      between alpha/beta-methyl-d-glucopyranose and beta-phenyl-d-glucopyranose with
      phenol, and the chromophore of tyrosine, using a combination of mass-resolved
      laser electronic spectroscopy in supersonic expansions and quantum mechanical
      calculations. The structures of the complexes detected in the jet are stabilized
      by a subtle equilibrium between several types of weak interactions, among which
      the dispersion forces may tilt the balance. In particular, the small structural
      changes introduced by the orientation of the anomeric substituent are amplified
      by the interaction with phenol. Consequently, the number of conformational
      isomers detected experimentally is different for each system and they present
      also differences in the preferred solvation site. Furthermore, inclusion of
      entropic terms for the calculated structures is advisable to understand the
      energetic reasons for the detection of a small set of experimental conformational
      isomers.

PMID- 27039950
TI  - Cycloruthenated complexes: pH-dependent reversible cyclometallation and reactions
      with nitrite at octahedral ruthenium centers.
AB  - The pH-dependent reversible cyclometallation and reactions with nitrite in a near
      aqueous system of a related set of cyclometallated ruthenium(ii) bipyridyl
      complexes were investigated in detail. These complexes are [Ru(ppy)(bpy)2]PF6 (,
      bpy = 2,2'-bipyridine, Hppy = 2-phenylpyridine), [Ru(thpy)(bpy)2]PF6 (, Hthpy = 2
      (2-thienyl)pyridine), and [Ru(dfppy)(bpy)2]PF6 (, Hdfppy = 2-(2,4
      difluorophenyl)pyridine). As expected, reversible UV-Vis spectra of these three
      complexes in near-aqueous solutions can be achieved by treating with acid or
      base, which indicates a pH-dependent reversible cyclometallation. However, the
      addition of nitrite to acidic solutions of these complexes disturbed the
      reversible pH-dependent processes. Unexpected ruthenium complexes in the
      aforementioned system were then isolated and characterized using FT-IR, MS, (1)H
      NMR, and UV-Vis spectra, indicating that two reaction modes occurred at the
      ruthenium(ii) centers: (1) the insertion of NO into the ruthenium-aryl bond to
      form a ruthenium C-nitroso complex; and (2) the coordination of NO with the
      entire dissociation of one bipyridine to form a {Ru-NO}(6) complex, which is the
      first example involving the cleavage of Ru-N(?)N bonds in ruthenium bipyridyl
      complexes.

PMID- 27039951
TI  - Graphene-based artificial nacre nanocomposites.
AB  - With its extraordinary properties as the strongest and stiffest material ever
      measured and the best-known electrical conductor, graphene could have promising
      applications in many fields, especially in the area of nanocomposites. However,
      processing graphene-based nanocomposites is very difficult. So far, graphene
      based nanocomposites exhibit rather poor properties. Nacre, the gold standard for
      biomimicry, provides an excellent example and guidelines for assembling two
      dimensional nanosheets into high performance nanocomposites. The inspiration from
      nacre overcomes the bottleneck of traditional approaches for constructing
      nanocomposites, such as poor dispersion, low loading, and weak interface
      interactions. This tutorial review summarizes recent research on graphene-based
      artificial nacre nanocomposites and focuses on the design of interface
      interactions and synergistic effects for constructing high performance
      nanocomposites. This tutorial review also focuses on a perspective of the dynamic
      area of graphene-based nanocomposites, commenting on whether the concept is
      viable and practical, on what has been achieved to date, and most importantly,
      what is likely to be achieved in the future.

PMID- 27039952
TI  - Guidance on assessing the methodological and reporting quality of toxicologically
      relevant studies: A scoping review.
AB  - Assessments of methodological and reporting quality are critical to adequately
      judging the credibility of a study's conclusions and to gauging its potential
      reproducibility. To aid those seeking to assess the methodological or reporting
      quality of studies relevant to toxicology, we conducted a scoping review of the
      available guidance with respect to four types of studies: in vivo and in vitro,
      (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and
      human observational studies. Our aims were to identify the available guidance in
      this diverse literature, briefly summarize each document, and distill the common
      elements of these documents for each study type. In general, we found
      considerable guidance for in vivo and human studies, but only one paper addressed
      in vitro studies exclusively. The guidance for (Q)SAR studies and physico
      chemical studies was scant but authoritative. There was substantial overlap
      across guidance documents in the proposed criteria for both methodological and
      reporting quality. Some guidance documents address toxicology research directly,
      whereas others address preclinical research generally or clinical research and
      therefore may not be fully applicable to the toxicology context without some
      translation. Another challenge is the degree to which assessments of
      methodological quality in toxicology should focus on risk of bias - as in
      clinical medicine and healthcare - or be broadened to include other quality
      measures, such as confirming the identity of test substances prior to exposure.
      Our review is intended primarily for those in toxicology and risk assessment
      seeking an entry point into the extensive and diverse literature on
      methodological and reporting quality applicable to their work.

PMID- 27039953
TI  - Power Failure: Acromegalic Cardiomyopathy.

PMID- 27039945
TI  - Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular
      Disease.
AB  - BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL)
      cholesterol increase the risk of cardiovascular disease. Lowering both should
      reduce the risk of cardiovascular events substantially. METHODS: In a trial with
      2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate
      risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or
      placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per
      day) or placebo. In the analyses reported here, we compared the 3180 participants
      assigned to combined therapy (with rosuvastatin and the two antihypertensive
      agents) with the 3168 participants assigned to dual placebo. The first coprimary
      outcome was the composite of death from cardiovascular causes, nonfatal
      myocardial infarction, or nonfatal stroke, and the second coprimary outcome
      additionally included heart failure, cardiac arrest, or revascularization. The
      median follow-up was 5.6 years. RESULTS: The decrease in the LDL cholesterol
      level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined
      therapy group than in the dual-placebo group, and the decrease in systolic blood
      pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The
      first coprimary outcome occurred in 113 participants (3.6%) in the combined
      therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71;
      95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary
      outcome occurred in 136 participants (4.3%) and 187 participants (5.9%),
      respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness
      and dizziness were more common in the combined-therapy group than in the dual
      placebo group, but the overall rate of discontinuation of the trial regimen was
      similar in the two groups. CONCLUSIONS: The combination of rosuvastatin (10 mg
      per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day)
      was associated with a significantly lower rate of cardiovascular events than dual
      placebo among persons at intermediate risk who did not have cardiovascular
      disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca;
      ClinicalTrials.gov number, NCT00468923.).

PMID- 27039954
TI  - Mindfulness Meditation Modulates Pain Through Endogenous Opioids.
AB  - BACKGROUND: Recent evidence supports the beneficial effects of mindfulness
      meditation on pain. However, the neural mechanisms underlying this effect remain
      poorly understood. We used an opioid blocker to examine whether mindfulness
      meditation-induced analgesia involves endogenous opioids. METHODS: Fifteen
      healthy experienced mindfulness meditation practitioners participated in a double
      blind, randomized, placebo-controlled, crossover study. Participants rated the
      pain and unpleasantness of a cold stimulus prior to and after a mindfulness
      meditation session. Participants were then randomized to receive either
      intravenous naloxone or saline, after which they meditated again, and rated the
      same stimulus. RESULTS: A (3) * (2) repeated-measurements analysis of variance
      revealed a significant time effect for pain and unpleasantness scores (both P
      <.001) as well as a significant condition effect for pain and unpleasantness
      (both P <.2). Post hoc comparisons revealed that pain and unpleasantness scores
      were significantly reduced after natural mindfulness meditation and after
      placebo, but not after naloxone. Furthermore, there was a positive correlation
      between the pain scores following naloxone vs placebo and participants'
      mindfulness meditation experience. CONCLUSIONS: These findings show, for the
      first time, that meditation involves endogenous opioid pathways, mediating its
      analgesic effect and growing resilient with increasing practice to external
      suggestion. This finding could hold promising therapeutic implications and
      further elucidate the fine mechanisms involved in human pain modulation.

PMID- 27039955
TI  - Demographics and Epidemiology of Sudden Deaths in Young Competitive Athletes:
      From the United States National Registry.
AB  - BACKGROUND: Sudden deaths in young competitive athletes are tragic events, with
      high public visibility. The importance of race and gender with respect to sport
      and the diagnosis and causes of sudden death in athletes has generated
      substantial interest. METHODS: The US National Registry of Sudden Death in
      Athletes, 1980-2011, was accessed to define the epidemiology and causes of sudden
      deaths in competitive athletes. A total of 2406 deaths were identified in young
      athletes aged 19 +/- 6 years engaged in 29 diverse sports. RESULTS: Among the 842
      athletes with autopsy-confirmed cardiovascular diagnoses, the incidence in males
      exceeded that in females by 6.5-fold (1:121; 691 vs 1:787,392 athlete-years; P
      <=.001). Hypertrophic cardiomyopathy was the single most common cause of sudden
      death, occurring in 302 of 842 athletes (36%) and accounting for 39% of male
      sudden deaths, almost 4-fold more common than among females (11%; P <=.001). More
      frequent among females were congenital coronary artery anomalies (33% vs 17% of
      males; P <=.001), arrhythmogenic right ventricular cardiomyopathy (13% vs 4%; P =
      .002), and clinically diagnosed long QT syndrome (7% vs 1.5%; P <=.002). The
      cardiovascular death rate among African Americans/other minorities exceeded
      whites by almost 5-fold (1:12,778 vs 1:60; 746 athlete-years; P <.001), and
      hypertrophic cardiomyopathy was more common among African Americans/other
      minorities (42%) than in whites (31%; P <=.001). Male and female basketball
      players were 3-fold more likely to be African American/other minorities than
      white. CONCLUSIONS: Within this large forensic registry of competitive athletes,
      cardiovascular sudden deaths due to genetic and/or congenital heart diseases were
      uncommon in females and more common in African Americans/other minorities than in
      whites. Hypertrophic cardiomyopathy is an under-appreciated cause of sudden death
      in male minority athletes.

PMID- 27039956
TI  - Beach debris on Aruba, Southern Caribbean: Attribution to local land-based and
      distal marine-based sources.
AB  - Accumulation of marine (plastic) debris from local land-based and distal marine
      based sources along coastlines is a pressing modern issue. Hitherto, assessing
      the relative contribution of pollution sources through beach surveys is
      methodologically challenging. We surveyed ten beaches along the leeward and
      windward coastlines of Aruba (southern Caribbean) to determine differences in
      macro- and meso-debris densities. Differences were quantified using three
      metrics: 1) the gradient in macro-debris density away from the waterfront; 2) the
      proportion of plastic within macro-debris; 3) the meso-:macro-debris ratio.
      Overall 42,585 macro-debris items and 884 meso-debris items were collected. The
      density of near-shore macro-debris, proportion of plastic debris herein, and meso
      :macro-debris ratio were highest on the windward coastline. These results suggest
      that southern Caribbean windward coastlines are mainly exposed to debris
      originating from distal marine-based sources, and leeward coastlines to local
      land-based sources. Our metrics clearly reflect these differences, providing
      novel means to survey debris source origin. 

PMID- 27039957
TI  - The influence of substrate material on ascidian larval settlement.
AB  - Submerged man-made structures present novel habitat for marine organisms and
      often host communities that differ from those on natural substrates. Although
      many factors are known to contribute to these differences, few studies have
      directly examined the influence of substrate material on organism settlement. We
      quantified larval substrate preferences of two species of ascidians, Ciona
      intestinalis (cryptogenic, formerly C. intestinalis type B) and Botrylloides
      violaceus (non-native), on commonly occurring natural (granite) and man-made
      (concrete, high-density polyethylene, PVC) marine materials in laboratory trials.
      Larvae exhibited species-specific settlement preferences, but generally settled
      more often than expected by chance on concrete and HDPE. Variation in settlement
      between materials may reflect preferences for rougher substrates, or may result
      from the influence of leached chemicals on ascidian settlement. These findings
      indicate that an experimental plate material can influence larval behavior and
      may help us understand how substrate features may contribute to differences in
      settlement in the field. 

PMID- 27039958
TI  - Young of the year bluefish (Pomatomus saltatrix) as a bioindicator of estuarine
      health: Establishing a new baseline for persistent organic pollutants after
      Hurricane Sandy for selected estuaries in New Jersey and New York.
AB  - Atlantic coastal bays of the US are essential habitat for young of year bluefish
      (Pomatomus saltatrix). Their residence in these estuaries during critical life
      stages, high lipid content, and piscivory make bluefish an ideal bioindicator
      species for evaluating estuarine health. Individual whole fish from four
      estuaries impacted by Hurricane Sandy were collected in August 2013, analyzed for
      a suite of persistent organic pollutants (POPs) including polychlorinated
      biphenyls, polybrominated diphenyl ethers and organochlorine pesticides and
      evaluated using health metrics. Concentrations in whole bluefish differed by
      estuary; however, concentrations for many POPs decreased or were similar to those
      observed prior to the hurricane. Prevalence of the ectoparasitic gill isopod
      (Lironeca ovalis) varied by estuary and no relationships between contaminants and
      lesions were observed. Bluefish should be considered for monitoring programs and,
      if sampled frequently, could be an effective bioindicator of incremental and
      episodic changes in contaminants within aquatic food webs. 

PMID- 27039959
TI  - Pollution from EOLV dismantling and the corresponding countermeasures.
AB  - There are problems associated with dismantling vessels that have reached the end
      of their life, when pollution problems associated with the process need to be
      addressed. The first problem in "end-of-life vessels" (EOLV) is to define their
      legal frameworks. The second problem is their dismantlement for recycling of
      ships. In order to reduce the effects of pollution caused by EOLV dismantling,
      the International Maritime Organization (IMO) adopted the Hong Kong Convention on
      15 May 2009. While preparing for implementing the obligations under the Hong Kong
      Convention, China shall make effort on five aspects: (i) establish an ISRT for
      the safe and environmentally sound recycling of ships, (ii) improve the
      competitiveness of ship dismantling plants, (iii) strengthen international
      exchanges, (iv) amend the domestic laws and regulations, and (v) support from the
      China Classification Society. 

PMID- 27039960
TI  - Use of Arius thalassinus fish in a pollution biomonitoring study, applying
      combined oxidative stress, hematology, biochemical and histopathological
      biomarkers: A baseline field study.
AB  - The present field study aimed to determine the extent of pollution in the Red Sea
      coast of Yemen Republic using a battery of biomarkers in sea catfish, Arius
      thalassinus, originating from a reference site in comparison with a polluted
      site. We reported the concentration of heavy metals in some vital fish organs and
      their effects on the morphological, hematological, biochemical and oxidative
      stress biomarkers accompanied by the examination of histopathological
      alterations. The obtained results showed clear signs of stress in fish from a
      polluted site. Linear correlation analysis exhibited that the biomarkers response
      could be linked to the detected metals bioaccumulation. In addition, principal
      component analysis showed a clear separation of sampling sites in two different
      assemblages. Semi-quantitative analysis for the observed histopathological
      lesions revealed that gills were the most affected organs with signs of severe
      alterations. This field investigation provides a baseline data on pollution
      status in this region. 

PMID- 27039961
TI  - Frequency of 1-h post-load glucose >=155 mg/dl among individuals with different
      glucose tolerance conditions.

PMID- 27039962
TI  - The association of distal femur and proximal tibia shape with sex: The
      Osteoarthritis Initiative.
AB  - OBJECTIVES: Risk of knee osteoarthritis (OA) is much higher in women than in men.
      Previous studies have shown that bone shape is a risk factor for knee OA.
      However, few studies have examined whether knee bone shape differs between men
      and women. The purpose of the present study was to determine whether there are
      differences between men and women in knee bone shape. METHODS: We used
      information from the NIH-funded Osteoarthritis Initiative (OAI), a cohort of
      persons aged 45-79 at baseline who either had symptomatic knee OA or were at high
      risk of it. Among participants aged between 45 and 60 years, we randomly sampled
      340 knees without radiographic OA (i.e., Kellgren/Lawrence grade of 0 in central
      readings on baseline radiograph). We characterized distal femur and proximal
      tibia shape of these selected radiographs using statistical shape modeling (SSM).
      We performed linear regression analysis to examine the association between sex
      and each knee shape mode (proximal tibia and distal femur), adjusting for age,
      race, body mass index (BMI), and clinic site. RESULTS: The mean age was 52.7
      years (+/-4.3 SD) for both men and women. There were 192 female and 147 male
      knees for the distal femur analysis. Thirteen modes were derived for femoral
      shape, accounting for 95.5% of the total variance. Distal femur mode 1 had the
      greatest difference in standardized score of knee shape between females and males
      (1.04, p < 0.01); modes 3, 5, 6, 8, and 12 were also significantly associated
      with sex. For tibial shape, 191 female knees and 149 male knees were used for the
      analysis. Overall, 10 modes explained 95.5% of shape variance. Of the
      significantly associated modes in the proximal tibia, mode 2 had the greatest
      difference in standardized score of bone shape between males and females (-0.30,
      p = 0.01); modes 3 and 4 were also significantly associated. CONCLUSION: The
      shapes of the distal femur and proximal tibia that form the knee joint differ by
      sex. Additional analyses are warranted to assess whether the difference in risk
      of OA between the sexes arises from bone shape differences.

PMID- 27039963
TI  - Arthroscopic Transtendon Repair of Partial-Thickness Articular-Side Rotator Cuff
      Tears.
AB  - PURPOSE: To evaluate the clinical outcomes and complications in a series of
      patients with painful partial articular cuff tears treated with the arthroscopic
      transtendinous repair with a minimum 2-year follow-up. METHODS: Eighty patients
      with a mean age of 51 +/- 5.4 years who had undergone an arthroscopic transtendon
      repair for a painful articular-sided rotator cuff tear with a minimum of 2-year
      follow-up were contacted. Clinical outcomes using a patient-based questionnaire,
      the University of California at Los Angeles score, the American Shoulder and
      Elbow Surgeons score, and the visual analog scale were evaluated. Postoperative
      complications were also assessed. RESULTS: After arthroscopic repair, the
      University of California at Los Angeles scores improved from 13.6 to 31.5; the
      American Shoulder and Elbow Surgeons scores improved from 44.4 to 76.1; and the
      visual analog scale scores improved from 6.3 to 1.3 (P < .0001). A total of 92.5%
      of patients were satisfied with their results. Only 5 patients developed a
      postoperative adhesive capsulitis that responded favorably to physical therapy.
      Eleven patients had concurrent procedures performed at the time of surgery. We
      found no difference between these patients and those who had an isolated tendon
      repair. CONCLUSIONS: Arthroscopic transtendon repair of partial-thickness
      articular-side rotator cuff tears is a reliable procedure that can be expected to
      produce satisfactory functional improvements and pain relief in most patients
      with a low rate of complications in the midterm follow-up. Concurrent procedures
      performed at the time of supraspinatus repair do not change functional outcomes.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 27039964
TI  - Arthroscopic Fixation of Tibial Eminence Fractures: A Clinical Comparative Study
      of Nonabsorbable Sutures Versus Absorbable Suture Anchors.
AB  - PURPOSE: To compare clinical outcomes of arthroscopic therapy for tibial eminence
      fracture with nonabsorbable suture and absorbable suture anchor. METHODS: Between
      February 2010 and September 2012, a total of 60 tibial eminence fracture patients
      were treated with nonabsorbable suture fixation or absorbable suture anchor
      fixation under arthroscopy. Patients with tibial plateau fractures and other
      significant injuries, including osteochondral lesions, meniscal tear, and
      anterior cruciate ligament (ACL) or mutiligament injuries, were excluded from the
      study. Radiographs, anterior drawer test (ADT), Lachman test, Lysholm score, and
      International Knee Documentation Committee (IKDC) 2000 subjective score were
      employed to evaluate clinical outcomes in follow-up. RESULTS: A total of 41
      patients were analyzed. Among these patients, 22 were treated with nonabsorbable
      suture fixation and 19 with absorbable suture anchor fixation. According to the
      modified Meyers-McKeever classification, 15 cases were categorized as type II, 21
      as type III, and 5 as type IV fractures. The mean time from injury to surgery was
      7.1 days (range, 3 to 12 days). All patients were followed up for a median period
      of 33.7 months (range, 24 to 45 months). Radiographic evaluation showed optimal
      reduction immediately after operation and bone union within 3 months in all
      patients. At the final follow-up, there was no limitation of knee motion range in
      any patient. Grade II laxity was found in 2 cases from suture group and 1 from
      suture anchor group, showing no significant difference based on ADT (chi(2) =
      0.538, P = .764) and Lachman test (chi(2) = 0.550, P = .760). Lysholm and IKDC
      2000 subjective scores were significantly improved (P < .001). However, there
      were no significant differences in the improvement of Lysholm (t = 0.522, P =
      .604) and IKDC 2000 subjective scores (t = 0.644, P = .523) between the 2 groups.
      CONCLUSIONS: Nonabsorbable suture fixation and absorbable suture anchor fixation
      are equivalent techniques in terms of the clinical efficacy of arthroscopic
      tibial eminence fracture treatment. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study.

PMID- 27039965
TI  - Outcomes of Bankart Repairs Using Modern Arthroscopic Technique in an Athletic
      Population.
AB  - PURPOSE: To report a large number of highly active patients who underwent
      arthroscopic Bankart repair at our institution over the last decade. METHODS: A
      retrospective analysis of patients who underwent primary and revision
      arthroscopic Bankart repairs using bioabsorbable anchors was performed. Outcome
      measures included recurrence of dislocation, American Shoulder and Elbow Scores
      (ASES), Rowe, visual analog scale (VAS), return to sports, and satisfaction
      scores. RESULTS: A total of 94 shoulders met the inclusion criteria. The
      recurrence rate was 6/94 (6.4%) at a mean follow-up of 5 years (range, 3 to 8.3).
      The mean postoperative scores were as follows: ASES = 91.5/100; Rowe = 84.3/100;
      VAS = 0.8/10; satisfaction = 8.8/10. In those who attempted to return to sports,
      82.5% were able to return to the same level of competition. Statistical analyses
      revealed a significant increase in risk of recurrence among high school and
      recreational athletes. No recurrences were observed among professional or college
      level athletes. No significant difference in recurrence rates was observed in
      regards to age, time to surgery, type of athlete (collision v limited contact),
      repair of SLAP lesion, number of anchors, or revision surgery. CONCLUSIONS:
      Although several repair techniques exist for traumatic anterior shoulder
      instability, arthroscopic repair remains a viable option even in a highly active
      patient population. This study uniquely identified high school and recreational
      athletes at higher risk for recurrence. This is perhaps due to inferior shoulder
      development and technique as well as to limited access to postoperative physical
      therapy. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 27039966
TI  - Biomechanical Comparison of All-Suture Anchor Fixation and Interference Screw
      Technique for Subpectoral Biceps Tenodesis.
AB  - PURPOSE: To compare the biomechanical characteristics of the subpectoral Y-knot
      all-suture anchor fixation with those of the interference screw technique.
      METHODS: Sixteen fresh-frozen human cadaveric shoulders with a mean age of 67.6
      +/- 5.8 years (range, 52 to 74 years) were studied. The specimens were randomly
      grouped into 2 experimental biceps tenodesis groups (n = 8): Y-knot all-suture
      anchor or interference screw. The specimens were cyclically tested to failure by
      applying tensile forces parallel to the longitudinal axis of the humerus. A
      preload of 5 N was applied for 2 minutes prior to cyclic loading for 500 cycles
      from 5 to 70 N at 1 Hz; subsequently, a load-to-failure test at 1 mm/s was
      performed. The ultimate failure load, stiffness, displacement at cyclic and
      failure loading, and mode of failure were recorded. RESULTS: The all-suture
      anchor technique displayed values of ultimate failure load and stiffness
      comparable to that of the interference screw technique. The displacement at
      cyclic and failure loading of the all-suture anchor trials were significantly
      greater than the interference screw (P = .0002). The all-suture anchor specimens
      experienced anchor pullout and tendon tear equally during the trials, whereas the
      interference screw group experienced tendon tear in most of the cases and screw
      pullout in 2 trials. CONCLUSIONS: The Y-knot all-suture anchor fixation provides
      equivalent ultimate failure load and stiffness when compared with the
      interference screw technique in tenodesis of the proximal biceps tendon from a
      subpectoral approach. However, the interference screw technique demonstrates
      significantly less displacement in response to cyclic and failure loading.
      CLINICAL RELEVANCE: The all-suture anchor fixation is an alternative technique
      for subpectoral biceps tenodesis even at greater displacement when compared with
      the interference screw fixation during cyclic and failure loading.

PMID- 27039967
TI  - Intra-population dental morphological variability among the Prehispanic Maya.
AB  - The present paper proposes a new approach to the estimation of intra-site
      variability of dental morphological traits when they are dichotomized into
      presence vs absence. It rests on the assumption that (1) higher intra-site
      variability is the expression of intense population dynamics and gene flow; and
      (2) maximum variability is reached when each trait is expressed in the population
      with a frequency of 50%. The approach simulates the calculation of frequency of
      heterozygotes in Mendelian traits (2xiyi), where xi and yi are the frequency of
      presence and absence of the trait. For every population, the final value
      corresponds to the average of (2xiyi) calculated from all the scored traits. Two
      separate analyses were performed using 50 and 40 traits recorded in 11
      Prehispanic Maya skeletal collections from the Yucatan Peninsula. Resulting
      average values were related to the sites' positions within the region's social,
      political and economic sphere of influence. Dental collections that were obtained
      from important city centers or by grouping many sites from a single region
      present the highest values of internal variability, followed by sites known to
      have played an important role in trade activities or in other socio-political
      contexts. At the other end, dental collections that represent smaller communities
      or more isolated, kin-related groups are set at the lower ranks of internal
      variability. One-way ANOVA tests for both 50 and 40 variables show that sample
      means present significant differences between the extreme ends of the ranked set
      of samples.

PMID- 27039968
TI  - Isokinetic Torque Timing Parameters and Ceramides as Markers of Muscle
      Dysfunction in Systolic Heart Failure.

PMID- 27039969
TI  - Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune
      Mediated Diseases: A Systematic Review and Meta-analysis.
AB  - BACKGROUND & AIMS: Physicians frequently encounter patients with immune-mediated
      diseases and a history of malignancy. There are limited data on the safety of
      immunosuppressive therapy for these patients. Published studies have been small
      with few events, precluding robust estimates of risk. METHODS: We searched
      Medline, EMBASE, and conference proceedings for terms related to immune-mediated
      disease, immune-suppressive therapy, and cancer recurrence from inception to
      April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of
      patients with inflammatory bowel disease, and 1 of patients with psoriasis) and
      stratified studies by type of immune-suppressive therapy (monoclonal antibodies
      to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no
      immune suppression). A random-effects meta-analysis was performed to calculate
      the pooled incidence rates as well as risk differences between the various
      treatments. RESULTS: Our analysis included 11,702 persons contributing 31,258
      person-years (p-y) of follow-up evaluation after a prior diagnosis of cancer.
      Rates of cancer recurrence were similar among individuals receiving anti-TNF
      therapy (33.8 per 1000 p-y), immune-modulator therapy (36.2 per 1000 p-y), or no
      immunosuppression (37.5 per 1000 p-y), but were numerically higher among patients
      receiving combination immune suppression (54.5 per 1000 p-y) (P > .1 for all).
      Subgroup analysis of new and recurrent cancers separately, type of immune
      modulator therapy, or immune-mediated disease showed similar results, with no
      increase in risk. We found similar pooled incidence values for new or primary
      cancers when immunosuppression was initiated within 6 years (33.6 per 1000 p-y
      for immune-modulatory agents and 43.7 per 1000 p-y for anti-TNF agents) vs more
      than 6 years after the index cancer (32.9 per 1000 p-y for immune-modulatory
      agents, P = .86; and 21.0 per 1000 p-y for anti-TNF agents, P = .43).
      CONCLUSIONS: In a meta-analysis of 16 studies, we observed similar rates of
      cancer recurrence among individuals with prior cancer who received no
      immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination
      treatments. Prospective studies are needed to ascertain optimal intervals for re
      initiation of immune-suppressive therapies for individuals with specific cancers.

PMID- 27039970
TI  - Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis
      Differ With Stage of Portal Hypertension.
AB  - BACKGROUND & AIMS: Clearance of hepatitis C virus (HCV) via antiviral treatment
      changes the course of liver disease. We evaluated the benefit of sustained
      virologic response (SVR) in patients with HCV and cirrhosis without (stage 1) and
      with (stage 2) esophageal varices (EV). METHODS: We performed a prospective
      cohort study of 444 patients with HCV and compensated cirrhosis (218 with stage 1
      and 226 with stage 2 disease) treated with peg-interferon and ribavirin from June
      2001 through December 2009 at the University of Palermo, Italy and followed for a
      median of 7.6 years (range, 1-12.6 years). We used Cox regression analysis to
      identify variables associated with appearance or progression of EVs, development
      of hepatocellular carcinoma (HCC), liver decompensation, and overall survival.
      RESULTS: In the intention-to-treat analysis, 67 patients with stage 1 disease
      (30.7%) and 41 patients with stage 2 disease (18.1%) achieved an SVR (P = .003).
      Patients with stage 1 disease and an SVR were less likely to develop EVs than
      stage 1 patients without an SVR (hazard ratio [HR], 0.23; 95% confidence interval
      [CI], 0.11-0.48; P < .001). However, SVR did not affect whether patients with
      stage 2 disease developed further EVs (HR, 1.58; 95% CI, 0.33-1.03; P = .07, by
      log-rank test). An SVR was associated with lower risk for HCC (HR, 0.25; 95% CI,
      0.12-0.55; P < .001). Patients with stage 2 disease, regardless of SVR, were at
      greater risk than patients with stage 1 disease for liver decompensation (HR,
      2.82; 95% CI, 1.73-4.59; P < .001) or death (HR, 1.77; 95% CI, 1.12-2.80; P =
      .015). A lower proportion of patients with stage 1 disease and an SVR died from
      HCC (2.9%), compared with those without an SVR (11.9%) (P = .03) or developed
      liver decompensation (none vs 7.1% without an SVR; P = .009). A lower proportion
      of patients with stage 2 disease and an SVR died from causes secondary to HCC
      (2.0%) compared with those without an SVR (18.4%) (P = .003). Death from causes
      secondary to liver decompensation did not differ significantly between patients
      with stage 2 disease with or without an SVR (12.1% vs 25.4%; P = .15).
      CONCLUSIONS: In a prospective study of 444 patients with HCV and compensated
      cirrhosis, HCV eradication reduced risk for liver decompensation, HCC, and death,
      regardless of whether the patients had EVs.

PMID- 27039971
TI  - [Perceived needs of women regarding maternity. Qualitative study to redesign
      maternal education].
AB  - OBJECTIVES: To assess women's perceptions of their needs during the process of
      becoming a mother and identify what they want from maternal education. DESIGN:
      Qualitative study with focus groups. SETTING: Bizkaia health region, Basque
      Health Service (Osakidetza), Spain. PARTICIPANTS: Thirty one women were recruited
      consecutively by midwives at six Osakidetza health centres. METHODS: Four
      sessions were held from September to November 2010 in Bizkaia (Spain), the four
      groups being stratified by socioeconomic status and stage of the process
      (pregnancy vs. postnatal period). To collate the information related to the
      various topics discussed, we used manifest content analysis that was facilitated
      by use of ATLAS.ti software. RESULTS: The focus of the women worries changes over
      time. In early pregnancy, women's main concern was for "everything to go well".
      As the pregnancy progressed, they needed more emotional support and wanted to
      feel confident and be self-reliant to face their fears of the birth and care for
      their child. They needed greater accompaniment in the puerperium and less
      pressure concerning breastfeeding. They also wanted an extended programme of
      perinatal rather than just antenatal education, which was more participatory and
      flexible and greater participation of their partner. CONCLUSION: Women have the
      same social and family networks needs, regardless of cultural differences between
      Anglo-Saxon and Southern European countries. We recommend an perinatal education
      to empower women to manage their own health and that of their family and link the
      health system with other networks of personal and social support for women.

PMID- 27039972
TI  - A methodological pipeline for serial-section imaging and tissue realignment for
      whole-brain functional and connectivity assessment.
AB  - BACKGROUND: Understanding the neurobiological basis of cognition and behavior,
      and disruptions to these processes following injury and disease, requires a large
      scale assessment of neural populations, and knowledge of their patterns of
      connectivity. NEW METHOD: We present an analysis platform for large-scale
      investigation of functional and neuroanatomical connectivity in rodents.
      Retrograde tracers were injected and in a subset of animals behavioral tests to
      drive immediate-early gene expression were administered. This approach allows
      users to perform whole-brain assessment of function and connection in a semi
      automated quantitative manner. Brains were cut in the coronal plane, and an image
      of the block face was acquired. Wide-field fluorescent scans of whole sections
      were acquired and analyzed using Matlab software. RESULTS: The toolkit utilized
      open-source and custom platforms to accommodate a largely automated analysis
      pipeline in which neuronal boundaries are automatically segmented, the position
      of segmented neurons are co-registered with a corresponding image acquired during
      sectioning, and a 3-D representation of neural tracer (and other products)
      throughout the entire brain is generated. COMPARISON WITH EXISTING METHODS:
      Current whole brain connectivity measures primarily target mice and use
      anterograde tracers. Our focus on segmented units of interest (e.g., NeuN labeled
      neurons) and restricting measures to these units produces a flexible platform for
      a variety of whole brain analyses (measuring activation, connectivity, markers of
      disease, etc.). CONCLUSIONS: This open-source toolkit allows an investigator to
      visualize and quantify whole brain data in 3-D, and additionally provides a
      framework that can be rapidly integrated with user-specific analyses and
      methodologies.

PMID- 27039973
TI  - Moving average template subtraction to remove stimulation artefacts in EEGs and
      LFPs recorded during deep brain stimulation.
AB  - BACKGROUND: Deep brain stimulation (DBS) is a well established therapy to treat
      movement disorders such as Parkinson's disease. More recently it has also been
      discussed as a therapy for certain psychiatric diseases. However, during active
      DBS the recordings of local field potentials (LFP) and the electroencephalogram
      (EEG) can be corrupted by substantial spike-type artefacts which need to be
      removed before any analysis. NEW METHOD: Here, we present a new method that we
      term ' Moving Average Subtraction' (MAS) that removes DBS artefacts by
      subtracting adaptive DBS artefact templates from the artefact contaminated data.
      In particular we have developed a resampling technique which is more efficient
      than upsampling for a precise reconstruction of the artefact shape without the
      need to oversample the EEGs. RESULTS: By applying this method we can derive
      undistorted signals even in case of the low sampling frequencies that are usual
      in clinical recordings. We applied the new technique to 12 data sets recorded at
      the surface and in various brain structures [subthalamic nucleus (STN), pedunculo
      pontine nucleus (PPN), Globus pallidus internus (GPi)] with 7 patients. Our
      results demonstrate the suppression of artefact related activity at the basic and
      harmonic frequencies of DBS. COMPARISON WITH EXISTING METHOD(S): The new
      technique outperforms the non-adaptive template subtraction technique for the
      removal of high frequency artefact residuals without producing the spectral dips
      that occur with notch filter approaches. CONCLUSIONS: The new technique
      facilitates the analysis of higher frequency bands (Gamma activity) in LFPs and
      EEGs recorded during active DBS.

PMID- 27039974
TI  - Purification of alpha-synuclein containing inclusions from human post mortem
      brain tissue.
AB  - Comparison with existing methods. BACKGROUND: Neurodegenerative disorders affect
      a large proportion of the elderly population. A group of disorders, known as the
      alpha-synucleinopathies, are characterised by the presence of alpha-synuclein
      containing protein inclusions, such as Lewy Bodies (LBs) found in neurons from
      Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB), and Glial
      Cytoplasmic Inclusions (GCIs) found in oligodendrocytes from Multiple System
      Atrophy (MSA). The analysis of the protein composition of inclusions has been
      hindered by limitations of methods for isolating the inclusions from the
      surrounding tissue. METHOD: Four modifications were made to the published method
      for GCI purification by Gai et al. (1999) which were: collecting the entire
      inclusion-containing part of the Percoll gradient; lysis of nuclei prior to DNAse
      digestion; limited tryptic digestion to release inclusions from the cytoskeletal
      meshwork; and increased antibody and magnetic bead concentrations/volumes to
      capture the larger amounts of inclusions. RESULTS: The optimised method gave a 28
      fold increase in yield compared to the published method of Gai et al. (1999). A
      2D-DIGE comparison revealed a 3.8-fold increase in alpha-synuclein enrichment and
      a corresponding 5.2-fold reduction in tubulin contamination. This method was also
      successfully adapted to the purification of LBs from DLB tissue. A 2D-DIGE
      comparison of purified GCIs (n=2) revealed that GCIs consist of 11.7% alpha
      synuclein, 1.9% alpha-beta-crystallin and 2.3% 14-3-3 proteins compared to 8.5%,
      2.0% and 1.5% in LBs, respectively. CONCLUSIONS: This study has generated an
      improved method for the purification of alpha-synuclein-containing inclusions
      with a yield sufficient for multiple forms of analysis.

PMID- 27039975
TI  - Intramedullary Mg2Ag nails augment callus formation during fracture healing in
      mice.
AB  - Intramedullary stabilization is frequently used to treat long bone fractures.
      Implants usually remain unless complications arise. Since implant removal can
      become technically very challenging with the potential to cause further tissue
      damage, biodegradable materials are emerging as alternative options. Magnesium
      (Mg)-based biodegradable implants have a controllable degradation rate and good
      tissue compatibility, which makes them attractive for musculoskeletal research.
      Here we report for the first time the implantation of intramedullary nails made
      of an Mg alloy containing 2% silver (Mg2Ag) into intact and fractured femora of
      mice. Prior in vitro analyses revealed an inhibitory effect of Mg2Ag degradation
      products on osteoclast differentiation and function with no impair of osteoblast
      function. In vivo, Mg2Ag implants degraded under non-fracture and fracture
      conditions within 210days and 133days, respectively. During fracture repair,
      osteoblast function and subsequent bone formation were enhanced, while osteoclast
      activity and bone resorption were decreased, leading to an augmented callus
      formation. We observed a widening of the femoral shaft under steady state and
      regenerating conditions, which was at least in part due to an uncoupled bone
      remodeling. However, Mg2Ag implants did not cause any systemic adverse effects.
      These data suggest that Mg2Ag implants might be promising for intramedullary
      fixation of long bone fractures, a novel concept that has to be further
      investigated in future studies. STATEMENT OF SIGNIFICANCE: Biodegradable implants
      are promising alternatives to standard steel or titanium implants to avoid
      implant removal after fracture healing. We therefore developed an intramedullary
      nail using a novel biodegradable magnesium-silver-alloy (Mg2Ag) and investigated
      the in vitro and in vivo effects of the implants on bone remodeling under steady
      state and fracture healing conditions in mice. Our results demonstrate that
      intramedullary Mg2Ag nails degrade in vivo over time without causing adverse
      effects. Importantly, radiographs, MUCT and bone histomorphometry revealed a
      significant increase in callus size due to an augmented bone formation rate and a
      reduced bone resorption in fractures supported by Mg2Ag nails, thereby improving
      bone healing. Thus, intramedullary Mg2Ag nails are promising biomaterials for
      fracture healing to circumvent implant removal.

PMID- 27039976
TI  - Polyamphoteric flocculants for the enhanced separation of cellular suspensions.
AB  - The efficient concentration and separation of microorganisms from dilute culture
      suspensions is crucial to the success and productivity of many biotechnological
      processes. This article presents the design and characterization of
      polyamphoteric flocculants with a tunable, zwitterionic character for the
      enhanced separation of biocolloidal suspensions of yeast, wastewater, microalgae,
      and potentially other cellular systems. The polyamphoteric flocculants have
      overall molecular charges dependent upon the system pH, thereby providing a
      strong electrostatic attraction to the diverse but predominantly negatively
      charged cellular surfaces of the biological suspensions. The polyamphoteric
      flocculants with tailored charge character are shown to have higher flocculation
      efficiencies than comparable cationic polyelectrolytes, and have an enhanced
      ability to 1) adsorb to the diverse range of charge character in cellular
      suspensions, 2) operate over an extended range of suspension pHs, and 3) operate
      at lower flocculant concentrations. These enhanced flocculation properties are
      shown to arise, perhaps counterintuitively, due to interactions between the
      negatively-charged functionality on the flocculant and the predominantly
      negatively-charged biocolloids. STATEMENT OF SIGNIFICANCE: This article presents
      the design and characterization of polyamphoteric flocculants for the separations
      of biocolloidal suspensions of importance in the production of
      biopharmaceuticals, microalgal cultures for nutraceuticals and biofuels, and
      wastewater treatment. The polyamphoteric flocculants consist of tunable, mixed
      charges dependent upon system pH, thereby providing strong electrostatic
      attraction to the diversely-charged surfaces of cellular suspensions. Enhanced
      flocculation efficiencies are achieved, as compared to cationic polyelectrolyte
      flocculants, and result from the ability of polyampholytes to adsorb to a diverse
      range of charge character and operate over an extended range of pH conditions.

PMID- 27039977
TI  - Zwitterionic polymer functionalization of polysulfone membrane with improved
      antifouling property and blood compatibility by combination of ATRP and click
      chemistry.
AB  - The chemical compositions are very important for designing blood-contacting
      membranes with good antifouling property and blood compatibility. In this study,
      we propose a method combining ATRP and click chemistry to introduce zwitterionic
      polymer of poly(sulfobetaine methacrylate) (PSBMA), negatively charged polymers
      of poly(sodium methacrylate) (PNaMAA) and/or poly(sodium p-styrene sulfonate)
      (PNaSS), to improve the antifouling property and blood compatibility of
      polysulfone (PSf) membranes. Attenuated total reflectance-Fourier transform
      infrared spectra, X-ray photoelectron spectroscopy and water contact angle
      results confirmed the successful grafting of the functional polymers. The
      antifouling property and blood compatibility of the modified membranes were
      systematically investigated. The zwitterionic polymer (PSBMA) grafted membranes
      showed good resistance to protein adsorption and bacterial adhesion; the
      negatively charged polymer (PNaSS or PNaMAA) grafted membranes showed improved
      blood compatibility, especially the anticoagulant property. Moreover, the
      PSBMA/PNaMAA modified membrane showed both antifouling property and anticoagulant
      property, and exhibited a synergistic effect in inhibiting blood coagulation. The
      functionalization of membrane surfaces by a combination of ATRP and click
      chemistry is demonstrated as an effective route to improve the antifouling
      property and blood compatibility of membranes in blood-contact.

PMID- 27039978
TI  - Co-immobilization of adhesive peptides and VEGF within a dextran-based coating
      for vascular applications.
AB  - Multifunctional constructs providing a proper environment for adhesion and growth
      of selected cell types are needed for most tissue engineering and regenerative
      medicine applications. In this context, vinylsulfone (VS)-modified dextran was
      proposed as a matrix featuring low-fouling properties as well as multiple
      versatile moieties. The displayed VS groups could indeed react with thiol, amine
      or hydroxyl groups, be it for surface grafting, crosslinking or subsequent
      tethering of biomolecules. In the present study, a library of dextran-VS was
      produced, grafted to aminated substrates and characterized in terms of degree of
      VS modification (%VS), cell-repelling properties and potential for the oriented
      grafting of cysteine-tagged peptides. As a bioactive coating of vascular
      implants, ECM peptides (e.g. RGD) as well as vascular endothelial growth factor
      (VEGF) were co-immobilized on one of the most suitable dextran-VS coating
      (%VS=ca. 50% of saccharides units). Both RGD and VEGF were efficiently tethered
      at high densities (ca. 1nmol/cm(2) and 50fmol/cm(2), respectively), and were able
      to promote endothelial cell adhesion as well as proliferation. The latter was
      enhanced to the same extent as with soluble VEGF and proved selective to
      endothelial cells over smooth muscle cells. Altogether, multiple biomolecules
      could be efficiently incorporated into a dextran-VS construct, while maintaining
      their respective biological activity. STATEMENT OF SIGNIFICANCE: This work
      addresses the need for multifunctional coatings and selective cell response
      inherent to many tissue engineering and regenerative medicine applications, for
      instance, vascular graft. More specifically, a library of dextrans was first
      generated through vinylsulfone (VS) modification. Thoroughly selected dextran-VS
      provided an ideal platform for unbiased study of cell response to covalently
      grafted biomolecules. Considering that processes such as healing and angiogenesis
      require multiple factors acting synergistically, vascular endothelial growth
      factor (VEGF) was then co-immobilized with the cell adhesive RGD peptide within
      our dextran coating through a relevant strategy featuring orientation and
      specificity. Altogether, both adhesive and proliferative cues could be
      incorporated into our construct with additive, if not synergetic, effects.

PMID- 27039979
TI  - [The dangers of blue light: True story!].
AB  - The dangers of the blue light are the object of numerous publications, for both
      the scientific community and the general public. The new prolific development of
      light sources emitting potentially toxic blue light (415-455nm) ranges from LED
      (Light Emitting Diodes) lamps for interior lighting to television screens,
      computers, digital tablets and smartphones using OLED (Organic Light Emitting
      Diode) or AMOLED (Active-Matrix Organic Light Emitting Diode) technology. First
      we will review some technical terms and the main characteristics of light
      perceived by the human eye. Then we will discuss scientific proof of the toxicity
      of blue light to the eye, which may cause cataract or macular degeneration.
      Analysis of the light spectra of several light sources, from natural light to LED
      lamps, will allow us to specify even better the dangers related to each light
      source. LED lamps, whether used as components for interior lighting or screens,
      are of concern if they are used for extended viewing times and at short distance.
      While we can protect ourselves from natural blue light by wearing colored glasses
      which filter out, on both front and back surfaces, the toxic wavelengths, it is
      more difficult to protect oneself from LED lamps in internal lighting, the use of
      which should be restricted to "white warmth" lamps (2700K). As far as OLED or
      AMOLED screens are concerned, the only effective protection consists of using
      them occasionally and only for a short period of time. 

PMID- 27039980
TI  - [Long-term results of phacoemulsification in pseudoexfoliation syndrome].
AB  - INTRODUCTION: The prevalence of pseudoexfoliation syndrome is estimated at 8 % of
      all cataracts operated within our institution. The goal of our study was to
      describe the frequency of intraoperative and postoperative complications and long
      term anatomical and functional results of phacoemulsification in
      pseudoexfoliation syndrome. PATIENTS AND METHODS: A retrospective observational
      study of a series including 103 patients (107 eyes) with cataract associated with
      pseudoexfoliation syndrome admitted between January 2010 and September 2014. All
      patients underwent phacoemulsification. RESULTS: The average age of our patients
      was 72.5+/-6 years. The average initial corrected visual acuity was 0.52+/
      0.14LogMAR. The cataract was grade C3N3 in 58 % of cases. The pseudoexfoliation
      syndrome was bilateral in 69 % of cases. Pupillary dilatation was<=6mm in 54 % of
      cases. Among intraoperative complications, zonular dialysis was found in 1.8 % of
      cases. Posterior capsular rupture and vitreous loss was noted at 5.4 % of
      patients. The incidence of secondary cataract was 31.7 % at 12 months. The mean
      postoperative best corrected visual acuity was 0.13+/-0.15 LogMAR. DISCUSSION:
      The small pupil associated with high grade of the cataracts in our series
      explains the slightly higher frequency of intraoperative zonular dialysis.
      Cataract surgery by phacoemulsification allows for a statistically significant
      improvement in visual acuity (P<0.001). The incidence of secondary cataract, the
      main postoperative complication, is higher in our series compared to data in the
      literature. CONCLUSION: Pseudoexfoliation syndrome is common in our country.
      Functional results of phacoemulsification are very satisfactory, and secondary
      cataract is the main complication. A meticulous search for pseudoexfoliation is
      mandatory during the initial examination in order to reduce intraoperative
      complications. Careful removal of the cortex and systematic polishing of the lens
      capsule should limit the incidence of secondary cataracts.

PMID- 27039981
TI  - [Axenfeld-Rieger syndrome: Case report].

PMID- 27039983
TI  - Questioning Greek philosophy.

PMID- 27039982
TI  - Engineering virus-like particles as vaccine platforms.
AB  - Virus-like particles (VLPs) have been utilized as vaccine platforms to increase
      the immunogenicity of heterologous antigens. A variety of diverse VLP types can
      serve as vaccine platforms, and research has focused on engineering VLPs to
      improve their efficacy as vaccines, enhance their stability, and allow for more
      versatile display of antigens. Here, we review selected VLP vaccine platforms,
      highlight efforts to improve these platforms through structure-informed rational
      design, and point to areas of future research that will assist in these efforts.

PMID- 27039984
TI  - Energy conserving chemical defibrillation of ventricular fibrillation: A
      randomized two phase controlled blinded trial.
AB  - OBJECTIVES: Potassium cardioplegia-induced transient asystole may conserve
      myocardial energy, foster chemical defribrillation, and improve VF arrest
      outcome. A trial of potassium infusion with or without calcium reversal was
      conducted to test for improvement in intra-arrest VF waveform and post-ROSC
      hemodynamics. METHODS: Eighteen swine were randomized to three treatment arms in
      two phases. VF was electrically induced and untreated for 4min. The animals then
      received 6min of mechanical CPR. Blinded investigators infused two study
      medicines peripherally during this interval. One group received 1.5mEq/kg KCl
      with CPR initiation followed 3min later by CaCl 10% infusion 0.12cm(3)/kg, the
      second group received 1.5mEq/kg KCl without CaCl, and the third group received
      placebo infusions. Ten minutes post VF initiation, defibrillation was performed,
      as appropriate, followed by ACLS for continued arrest or observation for 30min if
      ROSC. AMSA change from before to 5min post study drug infusion was compared with
      nonparametric statistics. MAP post ROSC was compared using mixed linear
      regression analysis. RESULTS: Average normalized AMSA change was -0.15, -0.63,
      and +0.27 in the KCl, KCl+CaCl, and placebo groups, respectively (p=0.01). Three
      KCl+CaCl animals developed on organized rhythm chemically without electrical
      defibrillation. One, 3, and 4 animals in the KCl, KCl+CaCl, and placebo groups,
      respectively, survived post ROSC. Post ROSC, MAP decreased 1.8mmHg (95% CI -1.4
      to 5.1) min(-1) less in the KCl+CaCl group compared to placebo. CONCLUSIONS:
      Chemical defibrillation and ROSC are possible post potassium-induced asystole.
      Potassium followed by calcium reversal, but not potassium alone, led to ROSC and
      post-ROSC hemodynamics comparable to recommended therapy.

PMID- 27039985
TI  - Classification of ostrich sperm characteristics.
AB  - The success of assisted reproduction techniques is dependent on a sound
      foundation of understanding sperm characteristics to evaluate so as to improve
      semen processing. This study offers a descriptive basis for ostrich semen quality
      in terms of sperm function characteristics (SFC) that include motility, measured
      by computer assisted sperm analysis CASA (SCA((r))), viability (SYBR14/PI) and
      membrane integrity (hypo-osmotic swelling test). Relationships among these SFC's
      were explored and described by correlations and regressions. Certain fixed
      effects including the dilution of semen, season, year and male associated with
      semen collection were interpreted for future applications. The seasonal effect on
      sperm samples collected throughout the year suggested that it is prudent to
      restrict collections to spring and summer when SFC's and sperm concentration are
      maximized, compared to winter when these aspects of sperm quality are suppressed.
      Dilution of ejaculates helped to maintain important SFC's associated with
      fertilization success. The SFC's and sperm concentration varied among males, with
      specific males, having greater values for the percentage of motile (MOT) and
      progressively motile (PMOT) sperm, as well as sperm velocity (VCL, VSL, VAP) and
      linearity (LIN) variables. Males may thus be screened on these variables for
      inclusion in an artificial insemination (AI) programme to optimize fertility
      success rates. 

PMID- 27039986
TI  - Piperacillin concentration in relation to therapeutic range in critically ill
      patients--a prospective observational study.
AB  - BACKGROUND: Piperacillin levels after standard dosing have been shown frequently
      to be subtherapeutic, especially when renal clearance was augmented. Here, we
      aimed to determine if piperacillin was in its therapeutic range in a typically
      heterogeneous intensive care unit patient group, and also to describe target
      attainment dependent on daily dosage, creatinine clearance, and renal replacement
      therapy (RRT). METHODS: Sixty patients with severe infections were included in
      this monocentric prospective observational study. Patients received 4.5 g of
      piperacillin-tazobactam two to three times daily by intermittent infusion
      depending on renal function according to clinical guidelines. Over 4 days,
      multiple serum samples (median per patient, 29; in total, 1627) were obtained to
      determine total piperacillin concentrations using ultra-high-performance liquid
      chromatography/tandem mass spectrometry. RESULTS: A high heterogeneity of patient
      characteristics was observed (e.g., on day 1: creatinine clearance 2-233 mL/min
      and ten patients on RRT). Piperacillin trough levels showed inter-individual
      variation from 123 to >1785-fold on different study days. Each day, approximately
      50% and 60% of the patients had piperacillin levels below the target ranges 1 and
      2, respectively [defined for the calculated unbound piperacillin fraction
      according to the literature as 100% time above MIC (100%fT > MIC) (target range
      1) and >= 50%fT > 4 * MIC (target range 2); MIC = 16 mg/L]. Whereas only the
      minority of patients who received piperacillin-tazobactam three times daily (TID)
      reached target 1 (38% on day 1), most patients who received piperacillin
      tazobactam only twice daily (BID) because of severely impaired renal function
      reached this target (100% on day 1). Patients with RRT had significant higher
      percentages of fT > MIC. Zero percent, 55% and 100% of patients without RRT who
      received antibiotics TID reached target 1 when creatinine clearance was > 65
      mL/min, 30-65 mL/min and < 30 mL/min, respectively. In patients with causative
      strains only sensitive to piperacillin-tazobactam of all antibiotics given to the
      patient, piperacillin levels negatively correlated with CRP concentrations of day
      4 (p < 0.05). CONCLUSIONS: A dosage of 4.5 g piperacillin-tazobactam TID seems to
      be frequently insufficient in critically ill patients, and also in patients where
      renal function is mildly to moderately impaired. For these patients, prescription
      of 4.5 g piperacillin-tazobactam four times daily could be considered. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01793012. Registered 24 January 2013.

PMID- 27039990
TI  - A REDOR ssNMR Investigation of the Role of an N-Terminus Lysine in R5 Silica
      Recognition.
AB  - Diatoms are unicellular algae that construct cell walls called frustules by the
      precipitation of silica, using special proteins that order the silica into a wide
      variety of nanostructures. The diatom species Cylindrotheca fusiformis contains
      proteins called silaffins within its frustules, which are believed to assemble
      into supramolecular matrices that serve as both accelerators and templates for
      silica deposition. Studying the properties of these biosilicification proteins
      has allowed the design of new protein and peptide systems that generate
      customizable silica nanostructures, with potential generalization to other
      mineral systems. It is essential to understand the mechanisms of aggregation of
      the protein and its coprecipitation with silica. We continue previous
      investigations into the peptide R5, derived from silaffin protein sil1p, shown to
      independently catalyze the precipitation of silica nanospheres in vitro. We used
      the solid-state NMR technique 13C{29Si} and 15N{29Si} REDOR to investigate the
      structure and interactions of R5 in complex with coprecipitated silica. These
      experiments are sensitive to the strength of magnetic dipole-dipole interactions
      between the 13C nuclei in R5 and the 29Si nuclei in the silica and thus yield
      distance between parts of R5 and 29Si in silica. Our data show strong
      interactions and short internuclear distances of 3.74 +/- 0.20 A between 13C?O
      Lys3 and silica. On the other hand, the Calpha and Cbeta nuclei show little or no
      interaction with 29Si. This selective proximity between the K3 C?O and the silica
      supports a previously proposed mechanism of rapid silicification of the
      antimicrobial peptide KSL (KKVVFKVKFK) through an imidate intermediate. This
      study reports for the first time a direct interaction between the N-terminus of
      R5 and silica, leading us to believe that the N-terminus of R5 is a key component
      in the molecular recognition process and a major factor in silica morphogenesis.

PMID- 27039989
TI  - Resonance Raman Study of an Anion Channelrhodopsin: Effects of Mutations near the
      Retinylidene Schiff Base.
AB  - Optogenetics relies on the expression of specific microbial rhodopsins in the
      neuronal plasma membrane. Most notably, this includes channelrhodopsins, which
      when heterologously expressed in neurons function as light-gated cation channels.
      Recently, a new class of microbial rhodopsins, termed anion channel rhodopsins
      (ACRs), has been discovered. These proteins function as efficient light-activated
      channels strictly selective for anions. They exclude the flow of protons and
      other cations and cause hyperpolarization of the membrane potential in neurons by
      allowing the inward flow of chloride ions. In this study, confocal near-infrared
      resonance Raman spectroscopy (RRS) along with hydrogen/deuterium exchange,
      retinal analogue substitution, and site-directed mutagenesis were used to study
      the retinal structure as well as its interactions with the protein in the
      unphotolyzed state of an ACR from Guillardia theta (GtACR1). These measurements
      reveal that (i) the retinal chromophore exists as an all-trans configuration with
      a protonated Schiff base (PSB) very similar to that of bacteriorhodopsin (BR),
      (ii) the chromophore RRS spectrum is insensitive to changes in pH from 3 to 11,
      whereas above this pH the Schiff base (SB) is deprotonated, (iii) when Ser97, the
      homologue to Asp85 in BR, is replaced with a Glu, it remains in a neutral form
      (i.e., as a carboxylic acid) but is deprotonated at higher pH to form a blue
      shifted species, (iv) Asp234, the homologue of the protonated retinylidene SB
      counterion Asp212 in BR, does not serve as the primary counteranion for the
      protonated SB, and (v) substitution of Glu68 with an Gln increases the pH at
      which SB deprotonation is observed. These results suggest that Glu68 and Asp234
      located near the SB exist in a neutral state in unphotolyzed GtACR1 and indicate
      that other unidentified negative charges stabilize the protonated state of the
      GtACR1 SB.

PMID- 27039991
TI  - Cytotoxicity of three commercial mouthrinses on extracellular matrix metabolism
      and human gingival cell behaviour.
AB  - This study evaluated the effects of commercially available antiseptic mouthrinses
      on human gingival fibroblast and keratinocyte behaviour and metabolism. Three
      mouthrinses containing essential oil (EO), chlorhexidine (CHX) and amine
      fluoride/stannous fluoride (AFSF), were tested in an in vitro study. Human
      gingival fibroblasts and keratinocytes were washed with 10% or 30% concentration
      of the commercial mouthrinses and their effects on cell adhesion and
      proliferation were investigated as well as the specific gene expression of
      markers involved in oral mucosa metabolism. As markers of cell metabolism, type I
      and IV collagens, laminin, fibronectin, fibromodulin and integrins were studied
      with real-time PCR. Moreover, interleukin-1 secretion, one of the major pro
      inflammatory cytokines, was evaluated. The results showed that CHX significantly
      reduced fibroblast and keratinocyte substrate adhesion capacities and CHX and EO
      inhibited cell proliferation better than AFSF rinse. The gene expression of
      several matrix components and cell adhesion receptors was downregulated in cells
      washed with CHX and EO compared with those washed with AFSF rinse. In conclusion,
      the AFSF mouthrinse does not induce or induces to a lesser extent the onset of
      irritation and/or cytotoxicity than CHX or EO. These findings and those of future
      studies will enable us to gain further insight into the clinical significance and
      effects of commercial mouthrinses. Pending further investigations, clinicians
      should be aware of the potentially adverse effects of mouthrinses and warn their
      patients against making improper use of these products. 

PMID- 27039992
TI  - Thermally Stable and Sterilizable Polymer Transistors for Reusable Medical
      Devices.
AB  - We realize a thermally stable polymer thin film transistor (TFT) that is able to
      endure the standard autoclave sterilization for reusable medical devices. A
      thermally stable semiconducting polymer poly[4-(4,4-dihexadecyl-4Hcyclopenta[1,2
      b:5,4-b]dithiophen-2-yl)-alt[1,2,5]thiadiazolo [3,4c] pyridine], which is stable
      up to 350  degrees C in N2 and 200  degrees C in air, is used as channel layer,
      whereas the biocompatible SU-8 polymer is used as a flexible dielectric layer, in
      addition to conventional SiO2 dielectric layer. Encapsulating with in-house
      designed composite film laminates as moisture barrier, both TFTs using either
      SiO2 or SU-8 dielectric layer exhibit good stability in sterilized conditions
      without significant change in mobility and threshold voltage. After sterilization
      for 30 min in autoclave, the mobility drops only 15%; from as-fabricated mobility
      of 1.4 and 1.3 cm(2) V(-1) s(-1) to 1.2 and 1.1 cm(2) V(-1) s(-1) for TFTs with
      SiO2 and SU-8 dielectric layer, respectively. Our TFT design along with
      experimental results reveal the opportunity on organic/polymer flexible TFTs in
      sterilizable/reusable medical device application. 

PMID- 27039993
TI  - Reevaluating Muscle Biopsies in the Diagnosis of Pompe Disease: A Corroborative
      Report.
AB  - BACKGROUND: Previous reports suggest that although a diagnostic muscle biopsy can
      confirm the presence of Pompe disease, the absence of a definitive biopsy result
      does not rule out the diagnosis. METHODS: In this study, we reviewed patients
      with a limb-girdle syndrome who demonstrated nonspecific abnormalities of muscle,
      without evidence of the classical changes of acid maltase deficiency. These
      patients were rescreened for Pompe disease using dried blood spot (DBS) testing.
      RESULTS: Twenty-seven patients provided blood samples for the DBS test. Four
      patients underwent subsequent genetic testing. Genetic analysis demonstrated that
      one patient tested positive for Pompe disease and one patient had one copy of a
      pathogenic variant. CONCLUSIONS: In conclusion, the ability of a diagnostic
      muscle biopsy to definitively rule out the presence of Pompe disease is limited.
      There is a role for a screening DBS in all patients presenting with a limb-girdle
      syndrome without a clear diagnosis.

PMID- 27039994
TI  - [Preconceptional and perinatal challenges of pregnancy in women with epilepsy].
AB  - Reproductive-aged women with epilepsy may present a number of specific issues to
      be managed in daily clinical practice. The impact of epileptic seizures and
      antiepileptic therapy on pregnancy outcome and the risk of teratogenicity should
      be minimized, which require careful attention and cooperation between obstetric
      gynecologyst and neurologist. The aim of the present paper is to review the
      impact of epilepsy attack on fetus and the pathomechanism and teratogenic effect
      of antiepileptic drugs.

PMID- 27039995
TI  - [Evaluation of the diagnostic value of bedside ultrasonography in the emergency
      care].
AB  - INTRODUCTION: Rapid differential diagnosis of circulatory failure (shock) with
      unknown etiology is a daily challenge in the field of emergency medicine. The
      Rapid Ultrasound in Shock (RUSH) protocol is well known since 2010. With the use
      of targeted steps, the 4 forms of shock (cardiogen, distributive, obstructive,
      hypovolemic) can be separated in a few minutes. AIM: The aim of the authors was
      to evaluate the usefulness of the Rapid Ultrasound in Shock protocol for the
      diagnosis of different forms of shock. METHOD: The retrospective study included
      123 critically ill patients admitted to the Emergency Department of Markusovszky
      Hospital, Szombathely, Hungary. Detailed records were obtained from all patients.
      RESULTS: From the 123 crirically ill patients, 64 patients suffered from
      circulatory failure, while the remaining patients had acute severe chest or
      abdominal pain, or respiratory failure. CONCLUSIONS: Based on the results of the
      first evaluation of the Rapid Ultrasound in Shock protocol in Hungarian patients,
      the authors conclude that, the bedside ultrasonography has a great value in
      emergency medicine, and this the protocol is suitable for its integration into
      patient care and education of emergency medicine.

PMID- 27039996
TI  - [The shades of anti-Jo1 positive antisynthetase syndrome in a Hungarian cohort].
AB  - INTRODUCTION: In idiopathic inflammatory myopathies, the presence of anti-Jo-1
      antibody defines a distinct clinical phenotype (myositis, arthritis, interstitial
      lung disease, Raynaud's phenomenon fever, mechanic's hands), called
      antisynthetase syndrome. AIM: To determine the demographic data as well as
      clinical, laboratory and terapeutical features of anti-Jo1 positive patients,
      followed by the department of the authors. METHOD: The medical records of 49
      consecutive anti-Jo1 patients were reviewed. RESULTS: Demographic and clinical
      results were very similar to those published by other centers. Significant
      correlation was found between the anti-Jo-1 titer and the creatine kinase and C
      reactive protein levels. Distinct laboratory results measured at the time of
      diagnosis of the disease (C-reactive protein, antigen A associated with Sjogren's
      syndrome, positive rheumatoid factor), and the presence of certain clinical
      symptoms (fever, vasculitic skin) may indicate a worse prognosis within the
      antisyntetase positive patient group. CONCLUSION: In the cases above more
      agressive immunosuppressive therapy may be required.

PMID- 27039997
TI  - [Factors determining the selection of treatment options of complementary and
      alternative medicine].
AB  - INTRODUCTION: Complementary and alternative medicine have undoubtedly been
      gaining ground on the healthcare market, thus the vital question arises why
      patients choose these treatments, oftentimes at the cost of discontinuing the
      Western medical therapy. AIM: The aim of the authors was to investigate and
      scrutinize factors leading to the utilization of various alternative medical
      services. METHOD: The basis of this qualitative research was medical
      anthropological fieldwork conducted at a clinic of Traditional Chinese Medicine
      including participant observation (355 hours), unstructured interviews with
      patients (n = 93) and in-depth interviews (n = 14). RESULTS: Patients of
      alternative medical systems often do not receive a diagnosis, explanation or cure
      for their illness from Western medicine, or they do not agree with what they are
      offered. In other instances, patients choose alternative medicine because it
      exhibits a philosophical congruence with their already existing explanatory
      model, that is, previous concepts of world, man or illness. CONCLUSIONS: A
      particular therapy is always part of a cultural system and it is embedded in a
      specific psycho-social context, hence choice of therapy must be interpreted in
      accordance with this perspective.

PMID- 27039998
TI  - [Successful pregnancy in a patient with idiopathic pulmonary arterial
      hypertension. Case report].
AB  - Idiopathic pulmonary arterial hypertension is characterized by progressive
      increase in pulmonary arterial pressure and pulmonary vascular resistance which
      lead to right ventricular failure and death. Pregnancy in patients with
      idiopathic pulmonary arterial hypertension is contraindicated because of the high
      maternal and fetal mortality. The authors present a case of successful pregnancy
      and delivery of a patient with idiopathic pulmonary arterial hypertension in
      Hungary for the first time. The aim of the report was to demonstrate that
      management and treatment of idiopathic pulmonary arterial hypertension in a
      pregnant woman is a complex and multidisciplinary task that should involve
      obstetrician, cardiologist and anesthesiologist. Those patients who become
      pregnant and do not wish to terminate the pregnancy must be referred to obstetric
      centers where a multidiciplinary approach is taken.

PMID- 27039999
TI  - [Importance of compliance in nutritional management. Case report].
AB  - Disease-related malnutrition is usually caused by the joint action of the
      underlying disease itself and dietary deficiency. The consequences of
      malnutrition, if left untreated, are serious, causing a marked decline in
      physical and psychological health and function, and an increased rate of
      complications and decreased effectiveness of the medical treatments. In case a
      functional gastrointestinal tract is present, the recommended form of nutritional
      management is the use of oral nutritional supplements. However, just like to any
      other therapy, compliance to oral nutritional supplements is highly influenced by
      the consistency, taste, smell, volume consumed, and side effects. The aim of the
      present case report is to illustrate that nutritional management is a successful
      and effective treatment option of disease-related malnutrition when the selection
      of the oral nutritional supplement takes into consideration patient's preferences
      as well.

PMID- 27040001
TI  - Beyond the threshold.

PMID- 27040002
TI  - [Development of the community child-rearing support scale: Measuring supportive
      behavior among older adults].
AB  - OBJECTIVES: Isolation and anxiety among child-rearing mothers in Japan are a
      current social problem. Involving diverse people in the community is recognized
      as an important factor in successful child rearing. This study aimed to develop a
      scale to measure supportive behavior for child rearing among older adults in the
      community and examine its reliability and validity. METHODS: Items were selected
      to measure supportive behaviors for child rearing in the community in accordance
      with constructs introduced via literature reviews and a preliminary
      investigation. Participants were asked to evaluate the frequency of each behavior
      on a four-point scale in a mail-based survey. Of a random sample of 1,500
      individuals aged 60-69, living in the Tokyo metropolitan area, 813 (54%)
      responded. Construct validity and reliability of the scale were examined by a
      confirmatory factor analysis and Cronbach's reliability coefficient. The validity
      was also examined by clarifying whether the assumed positive associations between
      the scale and the following variables were observed: frequency of contact with
      community residents; the generativity scale, which measured concern for the next
      generation; and experience of child rearing measured by number of own children
      and level of support for grandchildren. Pearson's correlation and multiple
      regression analyses were performed for the analysis of the results. RESULTS: The
      literature review and preliminary investigation revealed three constructs of
      supportive behaviors: "children's security and sound growth," "instrumental
      support to parents," and "emotional support to parents." A second-order factor
      analysis that modeled "child-rearing support in the community" as a higher-order
      factor above these three factors showed a good model fit when one item was
      deleted. The reliability coefficient was high enough (alpha=0.87) with the
      remaining seven items. As expected, the total score positively and significantly
      correlated with the frequency of contact with residents, especially with the
      younger generation, including children and their parents; generativity score;
      number of children; and care for grandchildren. Multiple regression analyses
      revealed that the measured child-rearing support in the community was largely
      explained by the frequency of contact with the younger generation. However, being
      female, taking care of grandchildren, and a higher generativity correlated with a
      higher child-rearing support score even after controlling for the frequency of
      contact. CONCLUSION: Reliability and validity of the community child-rearing
      support scale, consisting of seven items, were confirmed. Further studies are
      required to show applicability of the scale to diverse communities and age
      groups, and investigate the effects of the measured supportive behaviors on the
      child-rearing generation.

PMID- 27040003
TI  - [The association between subjective symptoms and lifestyle habits among junior
      high school students a cross-sectional survey in Kumamoto, Japan].
AB  - OBJECTIVES: This study aimed to examine the association between subjective
      symptoms and lifestyle habits among junior high school students by using a cross
      sectional survey. METHODS: The survey was conducted during May-November 2012. The
      study subjects were 1229 adolescents (527 boys and 702 girls, age 12-13 years)
      from 10 junior high schools in Kumamoto Prefecture, Japan. Data from 1182
      students (500 boys and 682 girls; response rate 96.2%) were used for the
      analyses. School nurses measured students' body weights and heights. A self
      administered questionnaire examining dietary intake (FFQW82), subjective symptoms
      (12 items), lifestyle habits (18 items), and diet- and health-related topics (9
      items) was used. The 4 categories of each of the 12 subjective symptoms were
      classified into dichotomous variables (1=always or sometimes; 0=occasionally or
      never). The subjective symptom score was calculated as a total score by summing
      up the dichotomous variables for the 12 subjective symptoms. Associations were
      examined using a chi-square test, Student's t-test, Wilcoxon rank sum test, and a
      stepwise regression model. The structure of factors was examined by factor
      analysis (varimax rotation) and associations among the question items were
      examined by principal component analysis. A significance level of 5% (two-sided)
      was applied and SAS ver. 9.3 software was used for the analyses. RESULTS:
      Students' body weights and heights were mostly at or near national averages. The
      ratio of energy intake at breakfast, lunch, and dinner for the 1-day total energy
      intake (kcal) was respectively 2:3:4, indicating decreased energy intake at
      breakfast. The percent energy (%E) from fat of the 1-day total energy intake was
      29%E for boys and 30%E for girls. Using regression models, we found that the
      following lifestyle factors were significantly related to fewer subjective
      symptoms: "balanced diet," and "sleeping 6 hours or more per day" were for boys
      and girls, "regularly eating three meals a day," "strong appetite," and "having
      relaxation time" for girls. However, the following factors were significantly
      related to more subjective symptoms: "eating hurriedly," and "2 hours or more of
      watching television or playing video games" were for boys and girls, "cooking
      meals or sweets" for boys, "eating snacks and nighttime meals," and "eating
      dinner after 9 p.m.," and "preparing bento (boxed lunches)" for girls. Dietary
      intake was not significantly related to subjective symptoms. CONCLUSION: Findings
      from this study suggest that subjective symptoms are associated with lifestyle
      habits among junior high school students.

PMID- 27040004
TI  - [Smoking behavior and participation in screening for lung, gastric, and
      colorectal cancers].
AB  - OBJECTIVES: Early detection of cancer incidence and tobacco control are
      prioritized in the second-term of the Basic Plan for Promotion of Cancer
      Measures. However, the cancer screening rate is low and smoking prevalence high
      in Japan. Smokers may not participate in cancer screening, although they are a
      high-risk population for cancer mortality. This study examined whether smoking
      status, including number of cigarettes smoked per day and the Brinkman index
      (BI), was associated with participation in screening for lung, gastric, and
      colorectal cancers. METHODS: In 2011, we conducted a cross-sectional study in
      Osaka city: 2,016 subjects aged 40 to 64 (men, N=966; women, N=1,050) were
      analyzed (response rate=52.4%). We used multivariable logistic regression with
      stratification by sex to calculate odds ratios (ORs) for participation in
      screening for lung, gastric, and colorectal cancers according to smoking status,
      such as number of cigarettes smoked per day and the BI. RESULTS: Compared with
      non-current smokers, current smokers were less likely to participate in all
      cancer screenings. Men who currently smoke had significantly lower odds for
      gastric and colorectal cancer screening participation than non-current smokers
      (gastric : OR=0.71, P=0.036 ; colorectal : OR=0.67, P=0.012). Furthermore,
      compared with non-current smokers, men who smoked more than 20 cigarettes per day
      had significantly lower odds for all cancer screenings (lung: OR=0.61, P=0.009;
      gastric: OR=0.61, P=0.009; colorectal: OR=0.59, P=0.004). Similar results were
      observed in smokers with a BI?600 (lung: OR=0.55, P=0.006; gastric: OR=0.62,
      P=0.028; colorectal: OR=0.56, P=0.006). Among the women, significant associations
      between number of cigarettes smoked per day, BI, and colorectal cancer screening
      participation were observed (more than 20 cigarettes per day: OR=0.39, P=0.004;
      BI?400: OR=0.51, P=0.020). CONCLUSION: Current smokers were less likely to
      undergo cancer screening compared with non-current smokers. These associations
      were stronger in men with greater numbers of cigarettes smoked per day and a
      higher BI score. Because smokers do not receive cancer screening, they may be at
      higher risk for cancer mortality. Counseling at the chance of cancer screening
      should be considered as a good opportunity to provide useful information on
      smoking cessation, as well as to promote cancer screening participation.

PMID- 27040005
TI  - [Association between Service Utilization Patterns and Frailty in the Elderly
      Certified at the Support Level in the Long-term Care Insurance System].
AB  - OBJECTIVES: This cross-sectional study clarified the association between service
      utilization patterns and frailty in the elderly certified at the support level in
      Japan's long-term care insurance (LTCI) system. METHODS: We analyzed 710 subjects
      who completed in-home assessments and interviews from 1,033 elderly aged 65 and
      over living in Izumiotsu who had been certified at the LTCI support level in
      August 2014. The long-term service utilization data were collected from the local
      governmental office. Frailty was examined by the in-home structured assessment
      conducted by local health and welfare professionals. As frailty indicators, we
      measured subjects' frailty using the Kaigo-Yobo-Checklist (CL frailty), handgrip
      strength, body mass index, depression, and cognitive function. Long-term service
      utilization patterns were classified into five patterns: (1) home helper service
      only, (2) day care service only, (3) home helper and day care service, (4) one or
      more other services (using at least one other service regardless of home helper
      or day care), and (5) no service utilization. Odds ratios (ORs) of each frailty
      indicator were estimated by service utilization patterns by using logistic
      regression analyses adjusted for demographic characteristics, with the other
      services group as the reference category. RESULTS: Out of 710 subjects (100%),
      the proportions of the service utilization patterns were as follows: home helper
      service only, 17.9%; day care service only, 15.6%; home helper and day care
      service, 13.1%; one or more other services, 27.0%; and no service utilization,
      26.3%. The logistic regression analyses showed that compared with the one or more
      other services group, the day care service only group had lower odds of CL
      frailty (OR=0.57, 95% confidence interval (CI)=0.34 to 0.95) and lower odds of
      low handgrip strength (OR=0.59, 95% CI=0.35 to 1.00). The no service utilization
      group had lower odds of CL frailty (OR=0.50, 95% CI=0.32 to 0.79) and lower odds
      of low handgrip strength (OR=0.58, 95% CI=0.37 to 0.91). The home helper service
      only group had higher odds of low handgrip strength (OR=1.91, 95% CI=1.11 to
      3.29). CONCLUSION: Long-term service utilization patterns of the elderly
      certified at the support level in the LTCI system were associated with frailty.
      Classifying frailty characteristics by long-term service utilization patterns may
      be considered as a method to provide community-based resources and support for
      older adults in the community.

PMID- 27040006
TI  - Will TAVR Become the Predominant Method for Treating Severe Aortic Stenosis?

PMID- 27040007
TI  - The endocast of the one-million-year-old human cranium from Buia (UA 31), Danakil
      Eritrea.
AB  - OBJECTIVES: The Homo erectus-like cranium from Buia (UA 31) was found in the
      Eritrean Danakil depression and dated to 1 million years. Its outer morphology
      displays archaic traits, as well as distinctive and derived characters. The
      present study provides the description and metric comparison of its endocranial
      anatomy. MATERIALS AND METHODS: UA 31 was originally filled by a diffuse
      concretion. Following its removal and cleaning, the endocast (995 cc) was
      reconstructed after physical molding and digital scan. Its morphology is here
      compared with specimens belonging to different human taxa, taking into account
      endocranial metrics, cortical traits, and craniovascular features. RESULTS: The
      endocast is long and narrow when compared to the H. erectus/ergaster hypodigm,
      although its proportions are compatible with the morphology displayed by all
      archaic and medium-brained human species. The occipital areas display a
      pronounced bulging, the cerebellum is located in a posterior position, and the
      middle meningeal vessels are more developed in the posterior regions. These
      features are common among specimens attributed to H. erectus s.l., particularly
      the Middle Pleistocene endocasts from Zhoukoudian. The parietal lobes are
      markedly bossed. This lateral bulging is associated with the lower parietal
      circumvolutions, as in other archaic specimens. This pronounced parietal
      curvature is apparently due to a narrow cranial base, more than to wider parietal
      areas. CONCLUSIONS: The endocast of UA 31 shows a general plesiomorphic
      phenotype, with some individual features (e.g., dolichocephaly and rounded lower
      parietal areas) which confirm a remarkable degree of morphological variability
      within the H. erectus/ergaster hypodigm. Am J Phys Anthropol 160:458-468, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27040008
TI  - Impact of weekend admission on in-hospital mortality in severe community-acquired
      pneumonia patients in Japan.
AB  - BACKGROUND AND OBJECTIVE: Little is known about the consequences of weekend
      admission on the quality of care in patients with severe community-acquired
      pneumonia. We compared the outcomes of weekend versus weekdays' admission for
      these patients on risk-adjusted mortality. METHODS: Using a large nationwide
      administrative database, we analysed patients with severe pneumonia who had been
      hospitalized in 1044 acute care hospitals between 2012 and 2013. We compared risk
      adjusted in-hospital mortality of guideline-concordant care between patients
      admitted weekdays and patients admitted on weekends. RESULTS: The study sample
      comprised 17 342 patients admitted on weekdays and 6190 patients admitted on
      weekends. The mortality rate of the weekend admission group was significantly
      higher than that of the weekday admission group (23.7% vs 20.5%; P < 0.001). Even
      after adjusting for baseline patient severity and need for urgent care, weekend
      admissions were associated with higher mortality (odds ratio: 1.10; 95%
      confidence interval: 1.02-1.19). The implementation rates of guideline-concordant
      microbiological tests (including sputum cultures and urine antigen tests) were
      significantly lower in the weekend admission group. These tests were found to be
      associated with lower in-hospital mortality. CONCLUSION: Our findings showed that
      weekend admission was associated with increased mortality in patients with severe
      community-acquired pneumonia in Japan. This may have been influenced by lower
      implementation of microbiological testing.

PMID- 27040009
TI  - Pentacene based Onsager crosses.
AB  - A dearomatization/aromatization strategy accesses the tetrahedral (crosslike)
      pentacene tetramer (tetrakis(4-((6,13-bis(TIPS-ethynyl)pentacen-2
      yl)ethynyl)phenyl)silane). This molecular caltrop and one of its derivatives form
      amorphous thin films, demonstrating the impact of the 3D-tetramerization on the
      bulk morphology of the otherwise crystalline TIPS-pentacene. 

PMID- 27040010
TI  - Use of novel echocardiographic techniques to assess right ventricular geometry
      and function.

PMID- 27040011
TI  - Usefulness of HATCH score as a predictor of atrial fibrillation after coronary
      artery bypass graft.
AB  - BACKGROUND: Atrial fibrillation (AF) after coronary artery bypass graft (CABG)
      surgery is associated with increased morbidity and mortality. The HATCH score was
      originally devised to predict the progression of paroxysmal AF to persistent AF.
      AIM: To determine whether the HATCH score predicts the development of AF after
      CABG surgery. METHODS: The medical records of 284 consecutive patients, who
      underwent CABG surgery between January 2013 and December 2014, were
      retrospectively reviewed for the development of AF in the postoperative (POAF)
      period. The HATCH score, and clinical and echocardiographic parameters were
      evaluated for all patients. RESULTS: Seventy (25%) patients developed POAF. The
      HATCH scores were higher in the POAF group (2.8 +/- 1.8 vs. 1.1 +/- 1.2, p <
      0.001). The area of the HATCH score under the curve in the receiver operating
      characteristics analysis was 773 (95% CI 706-841, p < 0.001). When the HATCH
      score was 2 or more as a threshold, there was for POAF 72% sensitivity and 75%
      specificity. CONCLUSIONS: The results of the present study suggest that the HATCH
      score can be used to predict the development of POAF.

PMID- 27040012
TI  - Complete atrioventricular block after isolated aortic valve replacement.
AB  - BACKGROUND: Temporary atrioventricular (AV) conduction disturbances are a common
      complication following cardiac surgery, especially involving the aortic valve.
      Permanent complete AV block is a serious and rare complication. Its prevalence
      has been estimated at 3-6% of all patients undergoing aortic valve replacement.
      Identification of factors that affect the occurrence of complete AV block
      requiring permanent pacemaker implantation might help reduce the risk of this
      problem in the future. AIM: To evaluate clinical, anatomical and surgical factors
      that might affect occurrence of complete AV, resulting in the need for permanent
      pacemaker implantation. METHODS: In our prospective study, we analysed clinical
      data of consecutive 159 patients operated due to isolated aortic valve disease
      between February 2011 and March 2012. Patients with a pacemaker implanted before
      that time were excluded from the study. The main indication for surgery was
      aortic stenosis (n = 114, 71.7%). Infectious endocarditis was an indication in 6
      (3.8%) cases. Mean patient age was 65.3 +/- 11.4 years, and the proportion of
      males to females was 56.6%/43.4%. Overall, 135 (84.9%) patients had sinus rhythm
      preoperatively. All operations were performed using median sternotomy,
      cardiopulmonary bypass, and hypothermia at 30-32 degrees C. A biological
      prosthesis was implanted in 120 (70.4%) patients. Patients who needed an
      additional procedure such as another valve surgery, aortic surgery or coronary
      artery bypass grafting were excluded from the study. RESULTS: Permanent pacemaker
      implantation was required in 11 (6.9%) patients. The pacemaker was implanted
      after at least 7 days of complete AV block which was then considered permanent.
      Univariate analysis showed that permanent pacemaker implantation was associated
      with prolonged cardiopulmonary bypass time, prolonged aortic cross-clamp time,
      and the occurrence of electrolyte disturbances. Univariate logistic regression
      revealed that the need for permanent pacemaker implantation depended on 5 factors
      including prolonged cardiopulmonary bypass time, prolonged aortic cross-clamp
      time, larger size of the implanted valve prosthesis, endocarditis as the
      indication for surgery, and electrolyte disturbances. In both backward and
      forward stepwise multivariate regression models, two parameters, prolonged aortic
      cross-clamp time and the presence of electrolyte disturbances, correlated with
      the occurrence of complete AV block. CONCLUSIONS: Permanent complete AV block is
      a serious complication after aortic valve surgery. Of all analysed clinical,
      anatomical and surgical factors, prolonged cardiopulmonary bypass time, prolonged
      aortic cross-clamp time, larger size of the implanted valve prosthesis,
      endocarditis as the indication for surgery, and electrolyte disturbances were
      found to be statistically significant predictors of permanent pacemaker
      implantation.

PMID- 27040013
TI  - Links between parameters of long-term latent memory and progression from
      paroxysmal to permanent atrial fibrillation during a five-year observation
      period. A preliminary study.
AB  - BACKGROUND AND AIM: As cognitive function is the most vulnerable human feature,
      its impairment may precede the occurrence of symptoms of cardiovascular system
      disorders, e.g. atrial fibrillation (AF). In this way, cognitive impairment may
      not only be a complication of AF, but also a marker of its progression. This
      study aims to test this hypothesis. METHODS: Of 35 patients with AF, 23 (66%) had
      paroxysmal and 12 (34%) had permanent arrhythmia at the start of the study. At
      both the start of the study and after 5.86 +/- 3.7-7.05 years of follow-up, the
      following neuropsychological tests were performed using the Beck Depression
      Inventory, Parts A and B of the Trail Making Test, eight trials from the Rey
      Auditory Verbal Learning Test (RAVLT), and the Stroop test. RESULTS: Patients who
      maintained paroxysmal AF for the whole study observation period (n = 10) had a
      significantly greater score in the sixth (A6) and seventh (A7) RAVLT trials
      (pertaining to parameters of long-term latent memory) at the start of the study.
      An association between lower RAVLT A6 and A7 trial scores and the risk of
      paroxysmal arrhythmia progression to permanent AF was confirmed using the Cox
      proportional hazards regression model and Kaplan-Meier survival analysis.
      CONCLUSIONS: A better long-term latent memory RAVLT score was associated with a
      favourable prognosis of sinus rhythm maintenance. Cognitive impairment should be
      investigated in patients with AF for the purpose of evaluating the patient's
      prognosis, subclinical injury to the cardiovascular system, and the ability to
      comply with treatment.

PMID- 27040014
TI  - Transthoracic ultrasonic tissue indices identify patients with severe left
      anterior descending artery stenosis. Correlation with fractional flow reserve.
      Pilot study.
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the potential clinical
      application of ultrasonic tissue indices, with a focus on systolic strain (SS)
      and systolic strain rate (SSR) parameters derived from transthoracic
      echocardiography, in the assessment of left anterior descending artery (LAD)
      stenosis. METHODS: The data of 30 patients with significant LAD stenosis were
      analysed. All patients underwent transthoracic echocardiography to obtain
      systolic myocardial velocity (Sm), longitudinal SS, and SSR from basal, mid, and
      apical segments of anterior and inferior walls in two-chamber apical view.
      Severity of LAD obstruction was measured by means of fractional flow reserve
      (FFR) during coronary catheterisation. RESULTS: Systolic velocities, strain, and
      strain rate measured in basal, middle, and apical segments of the anterior left
      ventricular (LV) wall were lower when compared to those obtained from the
      corresponding, i.e. unaffected, inferior LV wall. There was a significant
      correlation between FFR and the value of SS, SSR characterising the apical LV
      segment of the anterior wall (r = -0.583, p = 0.01; r = -0.598, p = 0.01,
      respectively). Moreover, we found significant correlation between FFR and Sm in
      the mid-segment of the LV anterior wall (r = 0.611, p = 0.009). CONCLUSIONS: We
      conclude that SS and SSR obtained from the apical segment of the anterior LV wall
      may be related to the severity of LAD stenosis.

PMID- 27040015
TI  - Single-centre experience in surgery of acute aortic type A dissection and true
      aortic arch aneurysm.
AB  - BACKGROUND: Surgery of the aortic arch is challenging. AIM: To assess the results
      of aortic arch surgery. METHODS: Analysis of 172 patients operated on arch
      dissection (emergency group: 97 patients) or aneurysm (elective group: 75
      patients) between 2007 and 2014. Arch surgery was defined as a procedure
      requiring circumferential anastomosis at the level of the aortic arch or the
      descending aorta with the use of techniques of brain protection (deep hypothermic
      circulatory arrest [DHCA] or selective antegrade cerebral perfusion [SACP])
      and/or debranching of at least one supra-aortic vessel. RESULTS: Men predominated
      in both groups (> 70%). Men were younger in the emergency group (55 vs. 66 years;
      p < 0.008). The operative risk was higher in the emergency group (19.2% vs.
      12.5%; p < 0.001). Forty-nine per cent of the patients from the emergency group
      and 5% from the elective group were operated with antiplatelet therapy (p <
      0.001). Extended hemiarch procedure was performed in 79% (n = 77) in the
      emergency and 76% (n = 57) in the elective group. Total arch replacement was
      performed in 19 (21%) patients from the emergency and 18 (24%) patients from the
      elective group. In these patients debranching was performed in 68% of the
      emergency patients group and in 67% of the elective group. Elephant trunk
      procedure (classic/frozen) was performed in 53% (n = 10) from the emergency and
      in 78% (n = 14) of patients from the elective group. Aortic valve sparing surgery
      was performed in 20% of patients from the emergency and 9% from the elective
      group (p = 0.063). DHCA was performed in 58% (n = 43) of patients from the
      elective group and 39% (n = 37) from the emergency group. SACP was performed in
      61% (n = 58) of patients from the emergency and 42% (n = 31) from the elective
      group. Thirty-day mortality in the emergency group reached 33% (n = 32), and in
      the elective group 15% (n = 11; p = 0.007). In multivariate analysis, predictors
      of death in the emergency group were: Logistic EuroSCORE above 19.5%,
      extracorporeal circulation time above 228 min, and postoperative acute renal
      failure (ARF); and in the elective group: DHCA time above 26 min, rethoracotomy
      due to bleeding, and ARF. Follow-up was completed in 100% of patients in terms of
      vital status. The mean follow-up time of the patients from the emergency group
      was 24.3 +/- 27.10 (min 0, max 92) months, and from the elective group 30.3 +/-
      24.5 (min 0, max 99) months. During the follow-up period all-cause mortality in
      the emergency group was 43% (n = 42/97), and in the elective group it was 36% (n
      = 27/75). CONCLUSIONS: Early mortality in the emergency group was higher, while
      long-term mortality did not differ among the groups. Postoperative ARF is a
      critical predictor of mortality in both groups.

PMID- 27040016
TI  - Severe hypoglycaemia in elderly patients with type 2 diabetes and coexistence of
      cardiovascular history.
AB  - BACKGROUND: Hypoglycaemia is a condition that occurs when blood glucose levels
      fall below 3.9 mmol/L (70 mg/dL), while hypoglycaemic coma is usually associated
      with glycaemia around 1.1 mmol/L (20 mg/dL). Recurrent severe hypoglycaemia may
      result in permanent neurological disorders and also has a negative impact on the
      cardiovascular system. AIM: To evaluate the causes of severe hypoglycaemia in
      elderly patients with type 2 diabetes and coexistence of cardiovascular history.
      METHODS: We analysed retrospectively the history of 33 elderly patients with type
      2 diabetes and coexistence of cardiovascular history, who were admitted to our
      clinic due to severe hypoglycaemia with loss of consciousness. The mean age of
      the patients was 76.0 +/- 11.1 years, and the mean duration of diabetes was 12.0
      +/- 9.8 years. Glycated haemoglobin (HbA1c) was measured and the prevalence of
      cardiovascular diseases and therapeutic procedures were evaluated. RESULTS: In
      the group of patients with severe hypoglycaemia, the mean value of HbA1c was 6.3
      +/- 1.2% (44 +/- 13.1 mmol/mol), which indicates a mean glucose value below 7.8
      mmol/L (140 mg/dL). Ischaemic heart disease was diagnosed in 18 patients (eight
      had a history of myocardial infarction), and 22 patients had arterial
      hypertension. Severe hypoglycaemia requiring hospitalisation in elderly patients
      with type 2 diabetes and coexistence of cardiovascular history was related to
      insulin or sulfonylurea therapy. CONCLUSIONS: A low HbA1c level indicates
      inappropriate intensification of therapy and was associated with high risk of
      severe hypoglycaemic episodes in older people. The majority of severe
      hypoglycaemic episodes were observed in sulphonylurea or insulin-treated type 2
      diabetic patients.

PMID- 27040017
TI  - The role of HATCH score in predicting the success rate of sinus rhythm following
      electrical cardioversion of atrial fibrillation.
AB  - BACKGROUND: The HATCH score predicts the development of persistent and permanent
      atrial fibrillation (AF) one year after spontaneous or pharmacological conversion
      to sinus rhythm in patients with AF. However, it remains unknown whether HATCH
      score predicts short-term success of the procedure at early stages for patients
      who have undergone electrical cardioversion (EC) for AF. AIM: The present study
      evaluated whether HATCH score predicts short-term success of EC in patients with
      AF. METHODS: The study included patients aged 18 years and over, who had
      undergone EC due to AF lasting less than 12 months, between December 2011 and
      October 2013. HATCH score was calculated for all patients. The acronym HATCH
      stands for Hypertension, Age (above 75 years), Transient ischaemic attack or
      stroke, Chronic obstructive pulmonary disease, and Heart failure. This scoring
      system awards two points for heart failure and transient ischaemic attack or
      stroke and one point for the remaining items. RESULTS: The study included 227
      patients and short-term EC was successful in 163 of the cases. The mean HATCH
      scores of the patients who had undergone successful or unsuccessful EC were 1.3
      +/- 1.4 and 2.9 +/- 1.4, respectively (p < 0.001). The area of the HATCH score
      under the curve in receiver operating characteristics analysis was (AUC) 0.792
      (95% CI 0.727-0.857, p < 0.001). A HATCH score of two and above yielded 77%
      sensitivity, 62% specificity, 56% positive predictive value, and 87% negative
      predictive value in predicting unsuccessful cardioversion. CONCLUSIONS: HATCH
      score is useful in predicting short-term success of EC at early stages for
      patients with AF, for whom the use of a rhythm-control strategy is planned.

PMID- 27040018
TI  - The crystal structure of maleylacetate reductase from Rhizobium sp. strain MTP
      10005 provides insights into the reaction mechanism of enzymes in its original
      family.
AB  - Maleylacetate reductase plays a crucial role in catabolism of resorcinol by
      catalyzing the NAD(P)H-dependent reduction of maleylacetate, at a carbon-carbon
      double bond, to 3-oxoadipate. The crystal structure of maleylacetate reductase
      from Rhizobium sp. strain MTP-10005, GraC, has been elucidated by the X-ray
      diffraction method at 1.5 A resolution. GraC is a homodimer, and each subunit
      consists of two domains: an N-terminal NADH-binding domain adopting an alpha/beta
      structure and a C-terminal functional domain adopting an alpha-helical structure.
      Such structural features show similarity to those of the two existing families of
      enzymes in dehydroquinate synthase-like superfamily. However, GraC is distinct in
      dimer formation and activity expression mechanism from the families of enzymes.
      Two subunits in GraC have different structures from each other in the present
      crystal. One subunit has several ligands mimicking NADH and the substrate in the
      cleft and adopts a closed domain arrangement. In contrast, the other subunit does
      not contain any ligand causing structural changes and adopts an open domain
      arrangement. The structure of GraC reveals those of maleylacetate reductase both
      in the coenzyme, substrate-binding state and in the ligand-free state. The
      comparison of both subunit structures reveals a conformational change of the
      Tyr326 loop for interaction with His243 on ligand binding. Structures of related
      enzymes suggest that His243 is likely a catalytic residue of GraC. Mutational
      analyses of His243 and Tyr326 support the catalytic roles proposed from
      structural information. The crystal structure of GraC characterizes the
      maleylacetate reductase family as a third family in the dehydroquinate synthase
      like superfamily. Proteins 2016; 84:1029-1042. (c) 2016 Wiley Periodicals, Inc.

PMID- 27040019
TI  - Pediatric Positional Sitting Dermatitis: A New Form of Pediatric Contact
      Dermatitis.
AB  - We report on four pediatric patients who presented with localized dermatitis in
      areas subject to repetitive friction due to their sitting positions. We propose
      that the cause of the eruption was irritant contact dermatitis due to frequently
      sitting in a crossed-leg sitting position, an entity for which we have coined the
      term pediatric positional sitting dermatitis (PPSD). The goal of this report is
      to raise clinicians' awareness of PPSD, which to our knowledge has not been
      previously described, and to discuss management of these patients. 

PMID- 27040020
TI  - The "Vessel through Strait" Sign is a Signature Radiological Sign for the
      Diagnosis of Left Hepatic Artery Variation.
AB  - An aberrant artery (AA) can frequently be observed coursing through the fissure
      for the ligamentum venosum (FLV) which was termed the "vessel through strait"
      sign (VTSS) by us. Fundamental data including the incidence, anatomical
      composition and clinical significance of VTSS and the AAs composing VTSS are
      still lacking. We sought to give a systematic demonstration on this issue in the
      present study. VTSS was respectively analyzed in 2,275 patients and was observed
      in 357 of them. Interestingly, 319 (89.4%) out of the 357 patients exhibiting
      VTSS were proved to have left hepatic artery variation (LHAV) (247 with replaced
      left hepatic artery, 64 with accessory left hepatic artery and 8 with variant
      common hepatic artery). We therefore hypothesized that VTSS could be a sign that
      strongly associated with LHAV and could be used for its diagnosis. In the
      following validating analysis, VTSS gained a sensitivity of 96.3% and a
      specificity of 98.3% for the diagnosis of LHAV in another bicenter cohort
      consisted of 1,329 patients. In conclusion, VTSS is a signature radiological sign
      of LHAV which could be used as an easy and specific method for the diagnosis of
      LHAV. 

PMID- 27040021
TI  - The WATCH (Weight Activity and Time Contributes to Health) paradigm and quality
      of life: the impact of overweight/obesity duration on the association between
      physical activity and health-related quality of life.
AB  - PURPOSE: Physical activity has been shown to reduce various health risks
      associated with obesity; however, it is less known how the duration of
      overweight/obesity impacts these associations. The purpose of this study was to
      determine how overweight/obesity status and overweight/obesity duration effects
      the association between physical activity and health-related quality of life
      (HRQOL). DESIGN: Cross-sectional and retrospective. SETTING: NHANES 2003-2006.
      SUBJECTS: One thousand five hundred and seventy-eight adults were included in
      this study. MEASURES: Moderate to vigorous physical activity was defined as >=
      2020 activity counts in a given minute for >= 150 min/week; HRQOL assessed from
      the CDC HRQOL-4 survey; present BMI was objectively measured and 10 year prior
      BMI was calculated using self-reported body mass. Six groups were created: (i)
      physically active, normal weight now and 10 years ago; (ii) physically inactive,
      normal weight now and 10 years ago; (iii) physically active, overweight/obese now
      but not 10 years ago; (iv) physically active, overweight/obese now and 10 years
      ago; (v) physically inactive, overweight/obese now but not 10 years ago and (vi)
      physically inactive, overweight/obese now and 10 years ago. ANALYSIS:
      Multivariable ordinal regression. RESULTS: In comparison to active individuals
      who were normal weight at the examination and 10 years prior, only those who were
      inactive and overweight at the examination and 10 years prior had a worse HRQOL;
      beta = 0.91 (95% CI: 0.20-1.63; p = 0.01). CONCLUSIONS: Among individuals who
      have been overweight/obese for longer durations, physical activity may help to
      improve HRQOL.

PMID- 27040022
TI  - Intra-ocular pressure fluctuation after cataract surgery in primary angle-closure
      glaucoma eyes medically controlled after laser iridotomy.
AB  - PURPOSE: To analyse the effect of cataract surgery on diurnal intra-ocular
      pressure (IOP) fluctuation in primary angle-closure glaucoma (PACG) eyes.
      METHODS: Thirty-nine eyes of 24 patients with PACG scheduled for cataract surgery
      were enrolled to this prospective study. A record was made which included mean
      IOP measurement, anterior chamber depth (ACD), anterior chamber angle (ACA),
      number of antiglaucomatous medications, visual field analysis (mean deviation -
      MD and pattern standard deviation - PSD) and responses to the Glaucoma Quality of
      Life-15 (GQL-15) questionnaires. The eyes were re-evaluated at 2 and 3 months of
      cataract surgery. RESULTS: IOP fluctuation was decreased from 4.58 +/- 2.07 mmHg
      to 2.84 +/- 1.5 mmHg (p < 0.001). The decrease in mean IOP, the number of
      glaucoma eye drops required (p < 0.001, p = 0.012, respectively) and the increase
      in mean ACD, ACA grading and SITA-standard MD (p < 0.001, p < 0.001, and p =
      0.01, respectively) were statistically significant. The mean GQL-15 score was
      also improved (p < 0.001). The change in IOP fluctuation correlated positively
      with the preoperative IOP fluctuation (r = 0.56 p = 0.00), the change in ACD (r =
      0.703, p < 0.001) and the change in ACA (r = 0.664, p < 0.001). In multivariate
      analysis, preoperative IOP fluctuation and postoperative increase in ACD were
      significantly associated with a reduction in IOP fluctuation of an average of 1.1
      mmHg per unit change (p = 0.00 and p = 0.019, respectively). CONCLUSIONS:
      Cataract surgery in PACG provides the opportunity to address many pathologies
      with one intervention; improving vision, diminishing IOP, blunting IOP
      fluctuation, reducing need for medications, eliminating a narrow angle and
      improving GQL-15 scores.

PMID- 27040024
TI  - "Womb with a View": The Introduction of Western Obstetrics in Nineteenth-Century
      Siam.
AB  - This article focuses on the historical confrontation between Western obstetrical
      medicine and indigenous midwifery in nineteenth-century Siam (Thailand).
      Beginning with the campaign of medical missionaries to reform Siamese obstetrical
      care, it explores the types of arguments that were employed in the contest
      between these two forms of expert knowledge. Missionary-physicians used their
      anatomical knowledge to contest both particular indigenous obstetrical practices
      and more generalized notions concerning its moral and metaphysical foundations.
      At the same time, by appealing to the health and well-being of the consorts and
      children of the Siamese elite, they gained access to the intimate spaces of
      Siamese political life. The article contends that the medical missionary campaign
      intersected with imperial desires to make the sequestered spaces of Siamese
      political life more visible and accessible to Western scrutiny. It therefore
      reveals the imbrication of contests over obstetrical medicine and trade diplomacy
      in the imperial world. 

PMID- 27040023
TI  - ADAMTS13 autoantibodies cloned from patients with acquired thrombotic
      thrombocytopenic purpura: 2. Pathogenicity in an animal model.
AB  - BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is a potentially
      fatal disease in which ultralarge von Willebrand factor (UL-VWF) multimers
      accumulate as a result of autoantibody inhibition of the VWF protease, ADAMTS13.
      Current treatment is not specifically directed at the responsible autoantibodies
      and in some cases is ineffective or of transient benefit. More rational,
      reliable, and durable therapies are needed, and a human autoantibody-mediated
      animal model would be useful for their development. Previously, TTP patient anti
      ADAMTS13 single-chain variable-region fragments (scFv's) were cloned that
      inhibited ADAMTS13 proteolytic activity in vitro and expressed features in common
      with inhibitory immunoglobulin G in patient plasma. Here, pathogenicity of these
      scFv's is explored in vivo by transfecting mice with inhibitory antibody cDNA.
      STUDY DESIGN AND METHODS: Hydrodynamic tail vein injection of naked DNA encoding
      human anti-ADAMTS13 scFv was used to create sustained ADAMTS13 inhibition in
      mice. Accumulation of UL-VWF multimers was measured and formation of platelet
      (PLT) thrombi after focal or systemic vascular injury was examined. RESULTS:
      Transfected mice expressed physiological plasma levels of human scFv and
      developed sustained ADAMTS13 inhibition and accumulation of unprocessed UL-VWF
      multimers. Induced focal endothelial injury generated PLT thrombi extending well
      beyond the site of initial injury, and systemic endothelial injury induced
      thrombocytopenia, schistocyte formation, PLT thrombi, and death. CONCLUSIONS:
      These results demonstrate for the first time the ability of human recombinant
      monovalent anti-ADAMTS13 antibody fragments to recapitulate key pathologic
      features of untreated acquired TTP in vivo, validating their clinical
      significance and providing an animal model for testing novel targeted therapeutic
      approaches.

PMID- 27040025
TI  - Hong Kong Junk: Plague and the Economy of Chinese Things.
AB  - Histories of the Third Plague Pandemic, which diffused globally from China in the
      1890s, have tended to focus on colonial efforts to regulate the movement of
      infected populations, on the state's draconian public health measures, and on the
      development of novel bacteriological theories of disease causation. In contrast,
      this article focuses on the plague epidemic in Hong Kong and examines colonial
      preoccupations with Chinese "things" as sources of likely contagion. In the
      1890s, laboratory science invested plague with a new identity as an object to be
      collected, cultivated, and depicted in journals. At the same time, in the
      increasingly vociferous anti-opium discourse, opium was conceived as a contagious
      Chinese commodity: a plague. The article argues that rethinking responses to the
      plague through the history of material culture can further our understanding of
      the political consequences of disease's entanglement with economic and racial
      categories, while demonstrating the extent to which colonial agents "thought
      through things." 

PMID- 27040026
TI  - Between the Bazaar and the Bench: Making of the Drugs Trade in Colonial India,
      ca. 1900-1930.
AB  - This article analyzes why adulteration became a key trope of the Indian drug
      market. Adulteration had a pervasive presence, being present in medical
      discourses, public opinion and debate, and the nationalist claim for government
      intervention. The article first situates the roots of adulteration in the
      composite nature of this market, which involved the availability of drugs of
      different potencies as well as the presence of multiple layers of manufacturers,
      agents, and distributors. It then shows that such a market witnessed the
      availability of drugs of diverse potency and strengths, which were understood as
      elements of adulteration in contemporary medical and official discourse. Although
      contemporary critics argued that the lack of government legislation and control
      allowed adulteration to sustain itself, this article establishes that the culture
      of the dispensation of drugs in India necessarily involved a multitude of
      manufacturer-retailers, bazaar traders, and medical professionals practicing a
      range of therapies. 

PMID- 27040027
TI  - Residential Treatment and the Invention of the Emotionally Disturbed Child in
      Twentieth-Century America.
AB  - In the 1930s, children who were violent, depressed, psychotic, or suicidal would
      likely have been labeled delinquent and sent to a custodial training school for
      punitive treatment. But starting in the 1940s, a new group of institutions
      embarked on a new experiment to salvage and treat severely deviant children. In
      the process, psychiatrists, psychologists, and social workers at these
      residential treatment centers (RTCs) made visible, and indeed invented, a new
      patient population. This article uses medical literature, popular media, and
      archival sources from several RTCs to argue that staff members created what they
      called the "emotionally disturbed" child. While historians have described the
      identification of the mildly "troublesome" child in child guidance clinics, I
      demonstrate how a much more severely ill child was identified and defined in the
      process of creating residential treatment and child mental health as a
      professional enterprise. 

PMID- 27040028
TI  - Introduction.

PMID- 27040029
TI  - Teaching Medical History with Primary Sources: Introduction.

PMID- 27040030
TI  - Teaching with Oral Histories.

PMID- 27040031
TI  - Teaching with Artifacts and Special Collections.

PMID- 27040033
TI  - Symptomatic, Magnetic Resonance Imaging-Confirmed Cervical Disk Herniation
      Patients: A Comparative-Effectiveness Prospective Observational Study of 2 Age-
      and Sex-Matched Cohorts Treated With Either Imaging-Guided Indirect Cervical
      Nerve Root Injections or Spinal Manipulative Therapy.
AB  - OBJECTIVE: The purpose of this study was to compare the outcomes of overall
      improvement, pain reduction, and treatment costs in matched patients with
      symptomatic, magnetic resonance imaging-confirmed cervical disk herniations
      treated with either spinal manipulative therapy (SMT) or imaging-guided cervical
      nerve root injection blocks (CNRI). METHODS: This prospective cohort comparative
      effectiveness study included 104 patients with magnetic resonance imaging
      confirmed symptomatic cervical disk herniation. Fifty-two patients treated with
      CNRI were age and sex matched with 52 patients treated with SMT. Baseline
      numerical rating scale (NRS) pain data were collected. Three months after
      treatment, NRS pain levels were recorded and overall "improvement" was assessed
      using the Patient Global Impression of Change scale. Only responses "much better"
      or "better" were considered "improved." The proportion of patients "improved" was
      calculated for each treatment method and compared using the chi(2) test. The NRS
      and NRS change scores for the 2 groups were compared at baseline and 3 months
      using the unpaired t test. Acute and subacute/chronic patients in the 2 groups
      were compared for "improvement" using the chi(2) test. RESULTS: "Improvement" was
      reported in 86.5% of SMT patients and 49.0% of CNRI patients (P = .0001).
      Significantly more CNRI patients were in the subacute/chronic category (77%)
      compared with SMT patients (46%). A significant difference between the proportion
      of subacute/chronic CNRI patients (37.5%) and SMT patients (78.3%) reporting
      "improvement" was noted (P = .002). CONCLUSION: Subacute/chronic patients treated
      with SMT were significantly more likely to report relevant "improvement" compared
      with CNRI patients. There was no difference in outcomes when comparing acute
      patients only.

PMID- 27040034
TI  - Best Practices for Chiropractic Care of Children: A Consensus Update.
AB  - OBJECTIVE: Chiropractic care is the most common complementary and integrative
      medicine practice used by children in the United States, and it is used
      frequently by children internationally as well. The purpose of this project was
      to update the 2009 recommendations on best practices for chiropractic care of
      children. METHODS: A formal consensus process was completed based on the existing
      recommendations and informed by the results of a systematic review of relevant
      literature from January 2009 through March 2015. The primary search question for
      the systematic review was, "What is the effectiveness of chiropractic care,
      including spinal manipulation, for conditions experienced by children (<18 years
      of age)?" A secondary search question was, "What are the adverse events
      associated with chiropractic care including spinal manipulation among children
      (<18 years of age)?" The consensus process was conducted electronically, by e
      mail, using a multidisciplinary Delphi panel of 29 experts from 5 countries and
      using the RAND Corporation/University of California, Los Angeles, consensus
      methodology. RESULTS: Only 2 statements from the previous set of recommendations
      did not reach 80% consensus on the first round, and revised versions of both were
      agreed upon in a second round. CONCLUSIONS: All of the seed statements in this
      best practices document achieved a high level of consensus and thus represent a
      general framework for what constitutes an evidence-based and reasonable approach
      to the chiropractic management of infants, children, and adolescents.

PMID- 27040035
TI  - The Effect of Chronic Pain Intensity on Sit-to-Stand Strategy in Patients With
      Herniated Lumbar Disks.
AB  - OBJECTIVE: Recurrent symptoms of low back pain and its transition to a chronic
      state are associated with specific motor strategies used by people to avoid pain.
      The aim of the study was to determine the impact of chronic pain intensity on sit
      to-stand (STS) strategy in chronic low back pain (CLBP) patients with herniated
      disks. METHOD: Vertical ground reaction forces (counter, peak, and postpeak
      rebound) and their respective times of occurrence were measured on 2 Kistler
      force plates. Thirty-two healthy persons served as a control group. People with
      CLBP (n = 40) were divided into 2 subgroups according to the reported pain
      intensity at rest as measured by the numeric pain rating scale (NRS): low pain
      (NRS <= 3) and high pain (HP; NRS > 3). RESULTS: Both CLBP subgroups achieved
      shorter time to counter force but longer time to postpeak rebound force (P <
      .01). The time to peak force was extended in HP on the right side (P < .01). HP
      presented lower peak force on the right and lower postpeak rebound force on the
      left side (P < .001) compared with controls. CONCLUSION: Patients with CLBP were
      characterized by an individual, compensatory STS movement strategy with shorter
      preparation and longer stabilization times. Avoidance behavior in STS execution
      was presented in HP individuals only, indicating that intensity of chronic pain
      was a significant factor in decreasing ground reaction peak force and increasing
      time to peak force.

PMID- 27040036
TI  - Nucleic Acid Nanostructures for Chemical and Biological Sensing.
AB  - The nanoscale features of DNA have made it a useful molecule for bottom-up
      construction of nanomaterials, for example, two- and three-dimensional lattices,
      nanomachines, and nanodevices. One of the emerging applications of such DNA-based
      nanostructures is in chemical and biological sensing, where they have proven to
      be cost-effective, sensitive and have shown promise as point-of-care diagnostic
      tools. DNA is an ideal molecule for sensing not only because of its specificity
      but also because it is robust and can function under a broad range of
      biologically relevant temperatures and conditions. DNA nanostructure-based
      sensors provide biocompatibility and highly specific detection based on the
      molecular recognition properties of DNA. They can be used for the detection of
      single nucleotide polymorphism and to sense pH both in solution and in cells.
      They have also been used to detect clinically relevant tumor biomarkers. In this
      review, recent advances in DNA-based biosensors for pH, nucleic acids, tumor
      biomarkers and cancer cell detection are introduced. Some challenges that lie
      ahead for such biosensors to effectively compete with established technologies
      are also discussed. 

PMID- 27040037
TI  - Pancreatic Panniculitis in an 18-Month-Old with Complete DiGeorge Syndrome.
AB  - Pancreatic panniculitis, characterized by tender, erythematous subcutaneous
      nodules occurring most commonly on the lower extremities, occurs in 2% of cases
      of pancreatic disease. We present a rare case of pancreatic panniculitis in a
      child with complete DiGeorge syndrome. 

PMID- 27040038
TI  - New sterically-hindered o-quinones annelated with metal-dithiolates:
      regiospecificity in oxidative addition reactions of a bifacial ligand to the Pd
      and Pt complexes.
AB  - An unusual reactivity of sterically hindered o-quinones with an annelated
      dithiete ring towards coordination at a dithiolene site has been discovered. New
      Pd and Pt dithiolate complexes have been synthesized. The reaction proceeds
      regioselectively, and the quinone site of the parent ligand is not affected even
      while using an excess of the metal complex. Both Pt and Pd complexes display a
      square planar surrounding for the metal ion and have very similar NMR, IR and
      UV/Vis spectra. Surprisingly, being coordinated at the dithiolene site to the
      metal, the ligand exhibits activity like an o-quinone, it could be reduced with
      different metals resulting in the corresponding o-semiquinonates which were
      confirmed by EPR spectroscopy. It was shown that an unpaired electron exhibits
      HFC with the phosphorus nuclei of phosphine ligands coordinated to the metal ions
      at the dithiolene site of the molecule.

PMID- 27040039
TI  - Evidence supporting laparoscopic major hepatectomy.
AB  - Laparoscopic liver resection (LLR) has been increasing in frequency with over
      9,000 cases done worldwide. Benefits of laparoscopic resection include less blood
      loss, smaller incisions, decreased postoperative morbidity, and shorter length of
      stay compared to open liver resection. With increased experience, several centers
      have reported series of laparoscopic major hepatectomy, although this represents
      only about 25% of total LLR performed. Evidence is accumulating to support
      laparoscopic major hepatectomy with the understanding that there is a steep
      learning curve, and surgeons should begin with minor LLR before moving on to
      laparoscopic major hepatectomy. Controversy still remains concerning indications,
      techniques, learning curve, risks, and long-term cancer outcomes with
      laparoscopic major hepatectomy. 

PMID- 27040040
TI  - Thickness-dependent photocatalytic performance of graphite oxide for degrading
      organic pollutants under visible light.
AB  - Photocatalysts use sustainable solar light energy to trigger various catalytic
      reactions. Metal-free nanomaterials have been suggested as cost-effective and
      environmentally friendly photocatalysts. In this work, we propose thickness
      controlled graphite oxide (GO) as a metal-free photocatalyst, which is produced
      by exfoliating thick GO particles via stirring and sonication. All GO samples
      exhibit photocatalytic activity for degrading an organic pollutant, rhodamine B
      under visible light, and the thickest sample shows the best catalytic
      performance. UV-vis-NIR diffuse reflectance absorption spectra indicate that
      thicker GO samples absorb more vis-NIR light than thinner ones. Density
      functional theory calculations show that GO has a much smaller band gap than that
      of single-layer graphene oxide, and thus suggest that the largely-reduced band
      gap is responsible for this trend of light absorption. 

PMID- 27040041
TI  - Effects of silymarin on biochemical and oxidative stress markers in end-stage
      renal disease patients undergoing peritoneal dialysis.
AB  - Introduction End-stage renal disease (ESRD) patients especially those undergoing
      dialysis are vulnerable to several complications, in particular those related to
      oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant
      in different pathologies. Methods To evaluate the effect of silymarin on
      biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal
      dialysis were randomly divided into two groups of silymarin (n = 28) and control
      (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months,
      respectively. Ferric reducing antioxidant power and total 8-iso-prostaglandin
      F2alpha were measured in plasma, while catalase enzyme activity was measured in
      erythrocytes of both groups before and after treatment. Findings Ferric reducing
      antioxidant power values after treatment were significantly decreased in
      silymarin group compared to before treatment values (17.2 +/- 2.9 and 15.9 +/-
      3.1 uM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase
      levels were increased 17.3% after silymarin consumption, while it was decreased
      9.1% in control group. Further, hemoglobin (from 10.94 +/- 2.17 to 11.54 +/- 2.03
      g/dL, P < 0.05) and albumin levels (from 3.48 +/- 0.67 to 3.61 +/- 0.53 g/dL, P <
      0.05) were significantly increased after silymarin administration. Discussion It
      is concluded that silymarin could be regarded as a supplementary therapy for ESRD
      patients undergoing peritoneal dialysis in order to reduce complications.

PMID- 27040042
TI  - Rare breast cancer: 246 invasive secretory carcinomas from the National Cancer
      Data Base.
AB  - BACKGROUND AND OBJECTIVES: Invasive secretory breast carcinoma (SBC) is a rare
      subtype of breast malignancy. METHODS: Cases of SBC and infiltrating ductal
      carcinoma (IDC) from the National Cancer Database (1998-2011) were queried.
      RESULTS: Patients with SBC (n = 246) and IDC were identified (n = 1,564,068). The
      group with SBC was younger (age 56.4 +/- 16.0 vs. 60.4 +/- 13.9 years, P <
      0.001), had similar tumor size (19.9 +/- 17.8 vs. 21.6 +/- 25.5 mm, P = 0.297),
      more frequently African-Americans (24.1 vs. 14.8 vs. 13.7; P = 0.004), more well
      differentiated (32 vs. 18%, P < 0.001) and less likely to be hormone receptor
      positive (ER: 64 vs. 76%, P = 0.001; PR: 43 vs. 65%, P < 0.001). No differences
      were found for incidence of node-positivity (32 vs. 34%, P = 0.520) and stage IV
      presentation (2.4 vs. 3.6%, P = 0.372). Breast conserving surgery (60 vs. 58%, P
      = 0.405) and hormonal therapy (67 vs. 71%, P = 0.489) rates were similar.
      Systemic chemotherapy was used less often for SBC (38 vs. 45%, P = 0.035). The
      overall survival of all patients with SBC was better than all patients with IDC
      (median not reached vs. 14.8 years, P = 0.025). CONCLUSION: SBC is an uncommon
      tumor that is often well-differentiated and seen in younger women. Contrary to
      prior reports, they are frequently hormone receptor-positive. Compared to IDC,
      overall survival is improved. J. Surg. Oncol. 2016;113:721-725. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27040043
TI  - Headache Education in Adult Neurology Residency: A Survey of Program Directors
      and Chief Residents.
AB  - OBJECTIVE: This cross-sectional study reassesses the status of headache didactics
      and clinical training in adult neurology residency programs in the United States
      to determine if program directors and chief residents feel that current training
      in headache is adequate. BACKGROUND: Headache is among the most common new
      complaints to both the neurology and primary care clinic and represents a
      significant economic burden. However, headache remains both under-diagnosed and
      under-treated. Of those who seek treatment only 28% report they are very
      satisfied with their management. One possible cause for dissatisfaction is
      inadequate education of treating physicians. Two studies in 2002 and 2005 that
      collectively surveyed all 125 adult neurology residency programs concluded that
      more evidence was needed to evaluate the adequacy of headache education in these
      programs. A survey of neurology residency department chairs and program directors
      in 2005 also evaluated the status of headache education in adult neurology
      training programs and concluded the same. METHODS: We surveyed 133 neurology
      residency program directors and 213 chief residents. Program directors and chief
      residents were asked about the amount of headache didactics, amount of clinical
      exposure to headache, perceived adequacy of current training and if plans existed
      to increase headache education through didactics or clinical exposure. RESULTS:
      Seventy-two program directors (54%) and 117 chief residents (55%) responded.
      Twenty-six percent of programs reported a mandatory headache clinic. Of these,
      35% of programs reported <2 weeks of clinic, 54% of programs reported 2-4 weeks,
      and 12% of programs reported > 4 weeks of clinic. Fifty-one percent of program
      directors felt more than 4 weeks of clinical exposure to headache was needed to
      adequately prepare neurology residents. Ninety-six percent of program directors
      surveyed believed their residents were adequately prepared to diagnose and treat
      headache disorders. Twenty-one percent had plans to increase didactic time and
      26% planned to incorporate more clinical exposure. CONCLUSIONS: Despite a modest
      increase in headache didactics in neurology residency programs over the last
      decade, many program directors and chief residents report that their programs do
      not include what they believe to be adequate educational experiences in headache.
      Although the overwhelming majority of neurology residency programs reported that
      residents were adequately prepared to diagnose and treat headache disorders,
      about a fourth of programs still felt the need to increase the amount of didactic
      and clinical exposure dedicated toward the management of headache disorders.

PMID- 27040044
TI  - Haemoglobin disorders in Australia: where are we now and where will we be in the
      future?
AB  - Inherited disorders of haemoglobin (Hb), such as thalassaemia and sickle cell
      disease (SCD) are common and responsible for significant morbidity and mortality
      on a global scale. As Australia becomes increasingly ethnically diverse, their
      prevalence will increase. However, we lack important demographic and
      epidemiological data to manage these disorders and their consequences and to
      support affected individuals and communities. Thalassaemia and SCD are lifelong
      conditions. Affected individuals have reduced life expectancies, poorer quality
      of life and complex healthcare needs. Treatment strategies currently focus on
      prenatal diagnosis, red blood cell transfusion, iron chelation, management of
      iron-related complications, haemopoietic stem cell transplantation (HSCT) and
      hydroxyurea. Currently, the only curative therapy is HSCT; however, gene therapy
      offers the possibility of cure and trials are currently underway. These therapies
      are associated with significant complications and substantial costs; there is
      also evidence of variation in approaches to diagnosis and care. Optimal
      strategies for many aspects of management are not yet defined and more research
      is necessary to inform clinical care and health service delivery. 

PMID- 27040045
TI  - Clinical Significance of High-intensity Zone for Discogenic Low Back Pain: A
      Review.
AB  - High-intensity zone (HIZ) was originally described as a high-intensity signal on
      T2-weighted magnetic resonance (MR) images, located in the posterior annulus
      fibrosus, clearly separated from the nucleus pulposus. Among symptomatic patients
      with low back pain, HIZ is present in 28-59% of cases. In morphologically
      abnormal discs, high sensitivity and specificity of 81% and 79%, respectively,
      were reported for HIZs and concordant pain during discography. In contrast,
      another report indicated low rates. Although most papers reported high
      sensitivity and specificity for this relationship, it remains controversial.
      Regarding the pathology of HIZs, inflammatory granulation tissues are found at
      sites showing HIZs. Such inflammatory tissues produce pro-inflammatory cytokines
      and mediators, which sensitize the nociceptors within the disc and cause pain. An
      effective treatment for this condition is yet to be established. Recently,
      minimally invasive surgery using percutaneous endoscopic discectomy (PED) under
      local anesthesia was introduced. After removal of the degenerated disc material,
      the HIZ is identified with the endoscope and then coagulated and modulated with a
      bipolar radio pulse. This technique is called thermal annuloplasty. In
      conclusion, HIZs is an important sign of painful intervertebral disc disruption,
      if identified precisely based on factors such as location and intensity.

PMID- 27040046
TI  - Optimizing baseplate position in reverse total shoulder arthroplasty in small
      sized Japanese females: technical notes and literature review.
AB  - The management of cuff tear arthropathy (CTA) has always been a challenge for
      shoulder surgeons. Introduction of reverse total shoulder arthroplasty (RTSA)
      helped in providing pain relief and improved shoulder function in patients with
      CTA. In this study, we aimed to evaluate the short-term clinical results and some
      clinical details regarding the types of available prosthesis, positioning, and
      size of the components for RTSA in a population of short-stature female Japanese.
      In our seven cases, the average glenoid size was 23.9 mm in width and 34.2 mm in
      height. The average width was smaller than the size of all available baseplates.
      We implanted reverse shoulder prostheses with baseplate that measured 28 mm in
      diameter and two locking screws. The center of the baseplate was shifted to allow
      slight anterior overhang relative to the anatomical center to avoid breakage of
      the posterior cortex and to achieve firm fixation. One case of humeral shaft
      fracture occurred while inserting the humeral stem and required encircling
      wiring. In our experience, the short term clinical results of RTSA were
      excellent, but a new prosthesis that is designed to fit the short stature of
      Asians with smaller glenoid and humerus should be considered.

PMID- 27040047
TI  - Factors complicating the diabetes management of visitors to Japan: advices from a
      Japanese National Center for overseas medical staff.
AB  - Linguistic, cultural, and geographical differences might challenge the management
      of diabetes patients travelling in a culturally and linguistically homogeneous
      country. This article presents an instructive case and identifies various factors
      that can help in effective diabetes management of such cases. A Russian female
      patient aged 23 came to Japan and visited our hospital for a second opinion
      regarding glycemic control. She was diagnosed with type 1 diabetes at age three
      and started insulin injections and diet therapy with carbohydrate counting
      methods. Her HbA1c level was 11.0% with multiple daily insulin injections. She
      showed neuropathy, nephropathy, and blindness due to her progressed retinopathy.
      Because of the language barrier, suggestions for lifestyle modification were not
      effectively conveyed to the patient. We analyzed possible barriers to effective
      diabetes management in such foreign patients. In addition to language barriers
      and difficulties in diet therapy, dissimilar diabetes treatment guidelines,
      inadequate healthcare insurance, and stress-inducing conditions can be barriers
      to effective diabetes management. Foreign diabetes patients might face several
      barriers in effective management while travelling in Japan. Use of medical
      interpreters, adequate medical insurance, and trained medical staff will help in
      overcoming these barriers.

PMID- 27040048
TI  - Recent great impact by an Isotope Separator On-Line (ISOL) in nuclear and
      radiochemistry.
AB  - On April 9 2015, the Letter article titled "Measurement of the first ionization
      potential of lawrencium, element 103" is now published at News and Views on
      Nature (2015) which has been performed by our remarkably Japanese colleagues of
      nuclear and radiochemistry at JAEA (Japan Atomic Energy Agency). In this review,
      the author will state that the isotope separator on-line (ISOL) our regularly
      used, one of mass separation techniques, with a thermal surface ionization makes
      possible for determining the ionization potential of lawrencium based on the
      fruitful fundations of developing the ISOL system until now and also ever
      studying searches for unknown nuclei and these nuclear decay properties around
      actinide region in the past 20 years.

PMID- 27040049
TI  - The intestinal microbiota and its role in human health and disease.
AB  - The role of the intestinal microbiota in human health is gaining more attention
      since clear changes in the composition of the intestinal bacteria or environment
      are seen in patients with inflammatory bowel disease, allergy, autoimmune
      disease, and some lifestyle-related illnesses. A healthy gut environment is
      regulated by the exquisite balance of intestinal microbiota, metabolites, and the
      host's immune system. Imbalance of these factors in genetically susceptible
      persons may promote a disease state. Manipulation of the intestinal microbiota
      with prebiotics, which can selectively stimulate growth of beneficial bacteria,
      might help to maintain a healthy intestinal environment or improve diseased one.
      In this review, analytical methods for identification of intestinal bacteria and
      an update on the correlation of the intestinal microbiota with human health and
      disease were discussed by introducing our recent studies to determine the
      prebiotic effects of a fiber-rich food in animal model and on healthy people and
      patients with ulcerative colitis (UC).

PMID- 27040050
TI  - Changes in foot function, disease activity, and disability after forefoot
      resection arthroplasty in patients with rheumatoid arthritis.
AB  - The purpose of this study was to investigate the changes in foot function,
      disease activity, and disability in patients with RA after resection arthroplasty
      of the forefoot (arthroplasty). Arthroplasty was performed on 11 patients with
      RA. All study patients underwent clinical assessment to measure disease activity
      (Disease Activity Score in 28 Joints-C-reactive protein, DAS28-CRP), disability
      (Health Assessment Questionnaire-Disability Index, HAQ-DI) and foot function
      (Foot Function Index, FFI) at the following stages: preoperatively and 1, 3, and
      12 months after surgery. Following arthroplasty, foot function improved
      significantly, as assessed by FFI total and subscales (pain, disability, and
      limitation of activity) (P<0.001, P<0.001, P<0.001, and P=0.002, respectively).
      Disease activity was significantly improved in relation to DAS28-CRP and its
      subscales of number of swollen joints and patient global assessment (PtGA)
      (P=0.033, P=0.008, and P=0.038, respectively). There was no significant
      difference in disability, as assessed by the HAQ-DI and its subscale, HAQ-walking
      (P=0.150 and P=0.597, respectively). Foot function improved significantly after
      arthroplasty, and was maintained at 12 months postoperatively. Additionally, our
      study showed that disease activity and its subscale PtGA improved after
      arthroplasty.

PMID- 27040051
TI  - Visualization of Lumbar Artery Variations by Contrast-Enhanced Multi-detector Row
      Computed Tomography.
AB  - PURPOSE: This study was designed to identify the anatomical variations of lumbar
      arteries on contrast-enhanced multi-detector row computed tomography (MDCT).
      MATERIALS AND METHODS: Consecutive 100 colon cancer patients underwent
      preoperative 3-dimensional navigation studies, which include CT colonography
      (CTC) and CT angiography (CTA) for evaluation of anatomical relationship between
      the colon cancer and mesenteric vasculatures. After exclusion of inappropriate
      cases, 84 cases (33 women and 51 men; mean age, 64 years) were finally analyzed.
      The visualization of lumbar arteries from the CTA was scored based on the
      agreement of two radiology specialists. Also the presence or absence of left and
      right common trunk of each lumbar artery was evaluated. RESULTS: Visualization
      scores on both sides of L1 were significantly lower than those of L2-L4. No
      significant difference could be found on visualization of L1 lumbar arteries
      between the young and the elderly group. The common trunk tended to be in the
      lower lumbar levels (L1 in 2.4%, L2 in 9.5%, L3 in 11%, and L4 in 23%).
      CONCLUSION: The development and variation of lumbar arteries can be evaluated
      with CTA. Furthermore, CTA can provide sufficient anatomical information on
      variations of the lumbar arteries prior to surgery or catheterization.

PMID- 27040052
TI  - Which muscle shows fasciculations by ultrasound in patients with ALS?
AB  - The purpose of the present study was to elucidate the relative frequencies of
      fasciculations assessed by sonography in a large number of muscles in patients
      with amyotrophic lateral sclerosis (ALS). The patients diagnosed as having ALS
      were retrospectively assessed by muscle sonography. The frequencies of having
      fasciculations were compared among the 15 muscles and the subtypes according to
      the initially affected body region. Overall, approximately half of the muscles
      had fasciculations (48.8%), in the average of 11.4 muscles per patient. The
      frequency of fasciculations tended to be lower in the patients with longer
      disease durations upon testing. Biceps brachii had the highest frequency,
      followed by extensor digitorum communis, whereas sternocleidomastoid and rectus
      abdominis had the lowest frequencies. The frequencies of fasciculations were
      similar among the clinical subtypes. In conclusion, in patients with ALS,
      fasciculations were detected most frequently in proximal arm muscles by
      sonography, whereas truncal muscles had lower frequencies. Fasciculations tended
      to be less evident in the advanced disease stage, possibly reflecting muscle
      degeneration. Appropriate selection of muscles to observe fasciculations is
      important for diagnosis of ALS.

PMID- 27040053
TI  - Sonographic evaluation of cervical nerve roots in ALS and its clinical subtypes.
AB  - Morphological assessment of peripheral nerves in amyotrophic lateral sclerosis
      (ALS) has been available by sonography. Detection of possible axonal atrophy
      could be important in predicting progression. Research on correlation between
      sonographic findings and clinical presentation has been sparse. The aim of the
      study was to assess possible motor axon loss in patients with ALS by sonography
      and to correlate the imaging features with clinical subtypes. Patients with
      either definite or probable ALS and control subjects had sonographic evaluation
      of the cervical nerve roots (C5, C6, and C7). Each diameter and their sums were
      measured. The ALS patients were classified by their clinical onset and
      progression (arm-onset, leg-onset, bulbar, and flail-arm variant) and the
      sonographic features were compared. Overall, the cervical nerve roots were
      thinner in ALS than in the controls, but the diagnostic sensitivity was low. The
      patients with arm dysfunctions tended to show thinner nerve roots than those with
      normal or relatively preserved arm functions. The four ALS subtypes showed
      similar diameters of the nerve roots. There was no correlation between the
      disease duration and the diameters of the nerve roots. Sonography of the cervical
      nerve roots showed axonal atrophy in ALS and potentially reflects subtle arm
      dysfunctions.

PMID- 27040054
TI  - Effects of gender and body weight on fibroblast growth factor 23 responsiveness
      to estimated dietary phosphorus.
AB  - Fibroblast growth factor 23 (FGF23) is a molecule involved in regulating
      phosphorus homeostasis. Although some studies indicated an association between
      serum FGF23 levels and sex, the association has not been fully investigated. The
      purpose of this study was to evaluate whether sex could influence FGF23
      responsiveness to dietary phosphorus intake in healthy individuals. Thirty two
      healthy subjects between 21 and 28 years were recruited for this study. Subjects
      performed 24-hour urine collection and blood samples were collected. We estimated
      phosphorus intake (UC-P) from the urine collection (UC), and evaluated any
      association between UC-P and serum FGF23 levels. Subsequently, we compared serum
      FGF23 levels between males and females. Positive correlation was observed between
      UC-P and serum FGF23 levels. Serum FGF23 levels were significantly higher in
      males than in females. Serum FGF23 levels/UC-P was significantly higher in
      females than in males. There was no significant difference in serum FGF23
      levels/UC-P/BW between the male and female groups. Our results indicate that
      there was no gender difference between FGF23 responsiveness to phosphorus intake
      per body weight.

PMID- 27040055
TI  - Combined treatment of UVA irradiation and antibiotics induces greater
      bactericidal effects on Vibrio parahaemolyticus.
AB  - The presence of antibiotics in the environment and their subsequent impact on the
      development of multi-antibiotic resistant bacteria has raised concerns globally.
      Consequently, much research is focused on a method to produce a better
      disinfectant. We have established a disinfectant system using UVA-LED that
      inactivates pathogenic bacteria. We assessed the bactericidal efficiency of a
      combination of UVA-LED and antibiotics against Vibrio parahaemolyticus. Combined
      use of antibiotic drugs and UVA irradiation was more bactericidal than UVA
      irradiation or antibacterial drugs alone. The bactericidal synergy was observed
      at low concentrations of each drug that are normally unable to kill the bacteria.
      This combination has the potential to become a sterilization technology.

PMID- 27040056
TI  - Short-Term Outcomes of Laparoscopic Distal Gastrectomy for Advanced Gastric
      Cancer.
AB  - The purpose of this study was to investigate the oncologic outcomes of
      laparoscopic distal gastrectomy (LDG) for advanced gastric cancer (AGC). Between
      April 2003 and March 2014, LDG was performed for 392 patients, 91 patients
      (23.2%) had histopathologically diagnosed AGC beyond T2 depth. The
      clinicopathological features, postoperative outcomes, mortality, morbidity,
      recurrence rate, and survivals of those patients were reviewed. The TNM stages of
      the tumor were IB in 26 patients (28.5%), IIA in 20 (21.9%), IIB in 18 (19.7%),
      IIIA in 13 (14.2%), IIIB in 6 (6.5%), IIIC in 6 (6.5%), and IV in 2 (2.1%). Major
      morbidity occurred in 14 patients (15.3%), with no postoperative mortality.
      Median follow-up was 24.5 months; 10 patients developed recurrence during the
      follow-up period, and 10 patients died, including 6 cancer deaths. The 5-year
      overall and disease-free survival rates were 76.8% and 72.6%, respectively. By
      stage, OS/DFS was 92.3%/91.8% in stage IB, 85.4%/85.4% in stage II, and
      49.3%/26.9% in stage III. Oncologic outcomes were good in patients with AGC,
      especially with stage IB-IIB, who underwent LDG. LDG appears to be an effective
      approach for treating stage IB and II gastric cancer.

PMID- 27040057
TI  - Prevalence of asthma and wheezes among snow crab workers in western Japan: a
      cross-sectional study.
AB  - OBJECTIVES: Few reports are available concerning the prevalence of asthma among
      snow crab workers in Japan. The object of this study was to estimate the
      prevalence of asthma and wheezes among Japanese snow crab workers and their
      associations with exhaled nitric oxide (FeNO) and YKL-40. METHODS: Forty-nine
      snow crab workers enrolled in this study, which was cross-sectional by design and
      was conducted using a translated version of the European Community Respiratory
      Health Survey questionnaire. The levels of FeNO and serum YKL-40 were measured
      between September and October 2014. RESULTS: The prevalences of current asthma
      and wheezes were 10.2% (95% CI, 3.4 to 22.2) and 12.2% (95% CI, 4.6 to 24.8),
      respectively. There was no association between these prevalences and the duration
      of snow crab employment. Six subjects' FeNO levels exceeded 50 ppb, and nine
      subjects' levels exceeded 25 ppb. Twelve subjects' (25.5%) serum YKL-40 levels
      exceeded 77.2 ng/mL, which was 2 standard deviations above the mean for healthy
      subjects. However, there were no significant relationships among the prevalences
      for asthma and wheezes, FeNO, and serum YKL-40. CONCLUSIONS: This study provides
      information concerning the prevalences of asthma and wheezes among Japanese snow
      crab processing workers.

PMID- 27040058
TI  - Isoflurane-induced postconditioning via mitochondrial calcium-activated potassium
      channels.
AB  - PURPOSE: Activation of the mitochondrial calcium-activated potassium (mKCa)
      channel reportedly confers resistance to myocardial ischemic stress. However, the
      role of the mKCa channel in postconditioning induced by volatile anesthetic
      remains unclear. METHODS: Male Japanese white rabbits underwent coronary artery
      occlusion for 30 min followed by reperfusion for 3 h. Volatile anesthetic,
      isoflurane, was administered at 3 min prior to reperfusion for 5 min. Rabbits
      were injected with the mKCa channel blocker, iberiotoxin, or the mKCa channel
      opener, NS1619, at 8 min prior to reperfusion. Myocardial infarct size and the
      area at risk (AAR) were measured at the end of the experiment. RESULTS:
      Isoflurane significantly reduced infarct size (23.0 +/- 9.8% of the AAR, P<0.05)
      compared with the control (44.0 +/- 9.1%). Iberiotoxin abolished the
      cardioprotective impact of isoflurane (43.0 +/- 11.6%), while iberiotoxin alone
      exerted no effect on infarct size (45.0 +/- 9.5%). NS1619 and isoflurane/NS1619
      both significantly reduced infarct size (21.0 +/- 10.3% and 19.0 +/- 8.8%,
      respectively, P<0.05 vs control group), but isoflurane/NS1619 showed no
      additional benefits compared with isoflurane alone. CONCLUSION: These results
      indicate that activation of the mKCa channel contribute isoflurane-induced
      postconditioning.

PMID- 27040059
TI  - The effect of dynamic stretching on hamstrings flexibility with respect to the
      spino-pelvic rhythm.
AB  - OBJECTIVES: To ascertain the dynamic stretch effects of flexibility of the
      hamstrings on lumbar spine and pelvic kinematics. BACKGROUND: Tight hamstrings
      are positively correlated with low back pain. However, it is unclear how
      flexibility of the hamstrings affects spino-pelvic rhythm. METHODS: Twelve
      healthy men participated in the study. The straight leg raising (SLR) angle,
      finger floor distance (FFD), and spino-pelvic rhythm was measured before and
      after the 6-week stretching protocol. The forward bending task was divided into 4
      phases. The paired t-test was used to determine significant differences before
      and after the FFD, SLR angle, lumbar motion, and pelvic motion, and spino-pelvic
      rhythm in each phase (p<0.05). RESULTS: After 6 weeks of stretching, significant
      improvements were seen in the FFD with maximum forward bending and in the SLR
      angle. Total pelvic rotation was also significantly increased in contrast to
      total lumbar flexion. A decreased spino-pelvic ratio was seen in the final phase.
      CONCLUSION: Dynamic stretching could change the spino-pelvic rhythm to a pelvis
      dominant motion, indicating that flexible hamstrings are important for preventing
      low back pain.

PMID- 27040060
TI  - Limited lymph node dissection in elderly patients with gastric cancer.
AB  - BACKGROUND: The number of elderly patients with gastric cancer is continuing to
      increase along with the life expectancy of the general population. The purpose of
      this study was to investigate both the impact of age on postoperative outcome and
      the effect of limited lymph node dissection for elderly patients. METHODS:
      Patients were classified into the following three groups: Group A, >=80 years old
      (n=44); Group B, 70-80 years old (n=139); Group C, <70 years old (n=219).
      Postoperative complication and survival rates were compared between the three
      groups Results: Limited lymph node dissection was performed significantly more
      frequently in Group A. In terms of surgery-related complications, no significant
      difference was seen between groups. In terms of general related complications,
      the complication rate increased with age, from 4% in Group C to 13% in Group B
      and 14% in Group A (p<0.05 each). Although limited lymph node dissection was
      frequently performed in Group A, cancer-specific survival showed no significant
      difference in R0 patients. CONCLUSIONS: Limited lymph node dissection for gastric
      cancer did not affect the cancer-specific survival in elderly patients.

PMID- 27040061
TI  - Development of a Breastfeeding Support Scale for Couples.
AB  - The aim of this study was to develop a Breastfeeding Support Scale for Couples
      (BSSC) and to examine its reliability and validity. The BSSC was designed to
      evaluate current state of mutual support necessary for breastfeeding from the
      perspective of wife as support recipient, and husband as support provider.
      Subjects were 324 wives who came for their 1-month postpartum checkup and their
      husbands. Valid responses obtained from 159 husbands (97.0%) and 303 wives
      (93.5%) were then subjected to analysis. The BSSC for husbands comprised of 10
      questions and two factors, and a scale for wives comprised of 14 questions and
      three factors were ultimately created. Cronbach's alpha reliability coefficient
      ranged from 0.72 to 0.89 for all factors for both husbands and wives. The
      internal consistency and criterion-related validity of the scale were also
      confirmed. The model fitted the data satisfactory. Its reliability and validity
      were confirmed. The BSSC focused on mutual support among married couples, and may
      reveal new directions for breastfeeding support by shedding light on the
      differences in the perception of reciprocity support. The BSSC can evaluate
      couples and the appropriate support necessary for breastfeeding from the
      perspective of reciprocity support.

PMID- 27040062
TI  - Cervical root sonography to differentiate multifocal motor neuropathy from ALS.
AB  - To explore suggestive evidence of focal proximal demyelination in multifocal
      motor neuropathy (MMN) without overt evidence of conduction block, we conducted
      sonographical assessment of cervical nerve roots in 9 MMN patients, 22 ALS
      patients, and 17 control subjects. The mean diameters of the C5 and C6 roots in
      MMN patients were significantly larger than those in ALS and controls, especially
      on the clinically dominant side. Although non-specific, sonography can be a
      potentially useful diagnostic procedure to support the diagnosis of MMN, even
      when overt conduction block is lacking.

PMID- 27040063
TI  - Prevalence of allergic rhinitis based on the SACRA questionnaire among Japanese
      nursing professionals with asthma.
AB  - Although adult asthma is attributable to occupational factors and asthma and
      rhinitis are related, relatively few studies have investigated the prevalence of
      occupational rhinitis based on occupation, and knowledge of occupational rhinitis
      in Japan is currently limited. The objective of this cross-sectional study was to
      estimate the prevalence of allergic rhinitis among Japanese nursing professionals
      with asthma. A postal survey was conducted from October to December 2013 using
      translated versions of the European Community Respiratory Health Survey for the
      prevalence of asthma and State of the Impact of Allergic Rhinitis on Asthma
      Control questionnaire for the prevalence of rhinitis. Of 4,634 Japanese nursing
      professionals, 497 subjects had asthma, and 270 of these 497 subjects had
      allergic rhinitis (54.3%; 95% confidence interval [CI], 49.7-58.7). Latex allergy
      was significantly associated with allergic rhinitis (odds ratio, 1.77; 95% CI,
      1.21-2.60). There was no relationship between employment period and prevalent
      allergic rhinitis. The results of this study provide fundamental information
      regarding occupational health among Japanese nursing professionals, including the
      prevalence of allergic rhinitis among Japanese nursing professionals with asthma
      and latex allergy as a potential risk factor for prevalent allergic rhinitis.

PMID- 27040064
TI  - Quantification of neuropathological findings by image data for the diagnosis of
      dementia in forensic autopsy cases.
AB  - The aim of the present study was to quantify neuropathological findings using
      image analysis software for the diagnosis of dementia in deceased who underwent
      forensic autopsy. Of the autopsies performed within 48 hours of death and
      excluding those of patients with head injury, thermal injury, heat stroke, or
      intracranial lesions, 8 were of autopsy cases clinically diagnosed with dementia
      and thus included in the dementia group (D). The non-dementia group (non-D)
      consisted of 6 deceased without dementia. To compare the D and non-D groups, 6
      regions and 7 types of pathological findings were observed semi-quantitatively
      using 4 conventional stainings. Quantitative analysis of collected image data was
      performed using image analysis software. Semiquantitative analysis of senile
      plaques and neurofibrillary tangles was performed with Bielschowsky-Hirano's
      silver staining image data. An easy, simple, and effective quantification method
      of the pathological findings was achieved. However, no significant differences
      were observed between the two groups, and diagnosis of dementia by the
      quantification of pathological findings was not successful. Diagnosis of dementia
      using image data may be possible in future studies with an increased number of
      autopsies, and by utilizing staining techniques with higher specificity and
      sensitivity, such as immunohistochemical staining.

PMID- 27040065
TI  - Stress fracture of the thoracic spine in an elite rhythmic gymnast: A case
      report.
AB  - Spondylolysis, a defect or stress fracture of the vertebral pars
      interarticularis, occurs most frequently in the lower lumbar spine and
      occasionally in the cervical spine, but is extremely rare in the thoracic spine.
      We report the case of a 17 year-old girl, an elite rhythmic gymnast, who reported
      with early-stage thoracic spondylolysis at T10 and T11 levels. Physicians should
      be aware that performance of unusual athletic movements, such as those by
      gymnasts, may lead to spondylolysis in rare locations.

PMID- 27040066
TI  - Complete Fracture-Dislocation of the Thoracolumbar Spine with No Critical
      Neurological Deficit: A Case Report.
AB  - Fractures at the thoracolumbar junction are the most common spinal column
      fractures. Among type C fractures in the Arbeitsgemeinschaft fur
      Osteosynthesefragen Spine Classification, cases with complete fracture
      dislocations of the spinal column often result in a critical neurological deficit
      despite surgical treatment. We present a case of an 18-year-old man who had a
      complete fracture-dislocation of the T12 vertebral body and multiple injuries
      following high-energy trauma but no critical neurological deficits. Because of
      active bleeding in the left thoracic cavity, the patient underwent open reduction
      of the T12 vertebral body and anterior spinal fusion of the T11-L1 vertebral
      bodies via an anterior approach between the T9 and T10 ribs within 24 h of the
      accident. Four months postoperatively, the patient could ambulate independently,
      with a slight disturbance of light touch. At 6 months postoperatively, plain
      computed tomography scans showed bony union of the T12 vertebral body. We
      postulated two reasons for the absence of critical neurological dysfunction: (1)
      spontaneous spinal canal sparing because of the fracture of the right superior
      articular process in the L1 vertebral body and (2) fracture morphology, that is,
      a rotational fracture with mild to moderately strong shearing stress to the dura
      mater.

PMID- 27040067
TI  - Accumulation and washout of 99mTc-sestamibi in osteoarthritic subchondral bone
      may indicate increased osteoclastic activity accompanying microfractures: a case
      study.
AB  - We show for the first time that imaging of osteoarthritic subchondral bone with
      99mTc-sestamibi (MIBI) may be a valuable diagnostic tool to assess the severity
      of subchondral sclerosis. This is a report on a patient who had osteoarthritis of
      both knees and where MIBI was accumulated in the lesion sites. Due to the
      accumulation of MIBI in the bone, we believe that excessive stress had been
      applied to the bone and microfractures had activated bone remodeling. Typically,
      MIBI accumulation is not observed in the bone, but MIBI is believed to exhibit
      high accumulation where there is an increased presence of osteoblasts and
      osteoclasts. Osteoclasts absorb calcium, consequently causing a depolarization of
      the mitochondrial membrane potential, which may decrease the ability to retain
      MIBI and enhance washout. Pathological examination of the tissues of this case
      confirmed an abundance of osteoclasts. This suggests that using MIBI may be
      useful for determining the increased presence of osteoblasts and osteoclasts.

PMID- 27040068
TI  - Arthroscopic excision of unstable os acromiale associated with impingement
      syndrome: a case report.
AB  - Os acromiale is a rare anatomical variant that is caused by failure of fusion of
      the acromial apophysis and is usually asymptomatic. We report a case of
      impingement syndrome of the left shoulder secondary to unstable os acromiale,
      which was initially overlooked and confirmed only during arthroscopic
      examination. Arthroscopic excision of the unstable fragment was successful
      without residual dysfunction of the deltoid muscle.

PMID- 27040069
TI  - Revision percutaneous endoscopic lumbar discectomy under the local anesthesia for
      the recurrent lumbar herniated nucleus pulposus in a high class athlete: A case
      Report.
AB  - Percutaneous endoscopic discectomy (PED) is a minimally invasive spinal technique
      and has several advantages compared with open surgery. We describe repeat PED
      surgery for recurrent herniated nucleus pulposus (HNP). The patient was a 33-year
      old handball high level player. Previously, he underwent transforaminal PED under
      local anesthesia for intracanalicular HNP at L4-5 level about 2 years ago. He
      could return to his original competitive level. Two years later, he felt low back
      and right leg pain again when he was playing handball. Magnetic resonance imaging
      revealed the recurrence of HNP at the same level. We conducted transforaminal PED
      again using the exact same route as the previous surgery. Although there was a
      little adhesion around the L5 nerve root, we could easily identify and remove the
      herniated mass using endoscopic forceps. Immediately after the surgery, the low
      back and leg pain disappeared. Repeat PED surgery for recurrence of lumbar disc
      herniation is effective especially for athletes because of the benefits of PED,
      including surgery under local anesthesia, preservation of normal posterior
      structures, less postoperative pain, early discharge, and faster return to
      sports.

PMID- 27040070
TI  - Early combined treatment with steroid and immunoglobulin is effective for serious
      Kawasaki disease complicated by myocarditis and encephalopathy.
AB  - Severe-type Kawasaki disease (KD) complicated by serious myocarditis and
      encephalopathy can be successfully treated without abnormality of the coronary
      arteries by steroid pulse treatment and intravenous immunoglobulin (IVIg). A 4
      year-old Japanese girl was diagnosed with KD due to a 6-day history of fever,
      rash, flushed lips, conjunctival hyperemia, palmar edema, and cervical
      lymphadenopathy. The day after initiation of IVIg and aspirin, cardiac gallop
      rhythm was identified. Cardiac ultrasonography revealed severe left ventricular
      dysfunction. Disturbance of consciousness, hallucinations, and slurred speech
      were also observed. Magnetic resonance imaging showed no abnormalities, but
      electroencephalography revealed high-voltage slow waves. Despite this serious
      disease, cardiac function and neurological abnormalities showed complete recovery
      without dilatation of the coronary arteries by steroid pulse treatment and
      additional IVIg. Follow-up at 15 months revealed no abnormality of the coronary
      arteries. In conclusion, we suggest that early combined treatment with steroid
      and IVIg is effective for serious KD complicated by myocarditis and
      encephalopathy.

PMID- 27040071
TI  - Efficacy of erlotinib and imatinib in a patient with a rectal gastrointestinal
      stromal tumor and synchronous pulmonary adenocarcinoma: A case report.
AB  - The synchronous existence of lung cancer and gastrointestinal stromal tumors
      (GIST) is considered to be extremely rare. To the best of our knowledge, this is
      the first report about the treatment of lung cancer and GIST with two kinds of
      molecular targeting drugs. An 83-year-old woman with a rectal GIST, which carried
      a c-kit mutation, and pulmonary adenocarcinoma, which exhibited an epidermal
      growth factor receptor (EGFR) mutation, was treated alternately with imatinib and
      erlotinib. Good control over both diseases was achieved for two years. The
      present case is not only of interest due to the rare co-occurrence of GIST and
      lung cancer, but also because it involved two tumors carrying different gene
      mutations, and both tumors were brought under control using different molecular
      targeting drugs.

PMID- 27040072
TI  - Safe and successful treatment with afatinib in three postoperative non-small cell
      lung cancer patients with recurrences following gefitinib/erlotinib-induced
      hepatotoxicity.
AB  - BACKGROUND: Gefitinib and/or erlotinib-induced hepatotoxicity sometimes lead to
      treatment failure in EGFR mutation-positive patients with non-small cell lung
      cancer (NSCLC), even though the therapeutic effect is evident. CASES: Here, we
      report three postoperative NSCLC patients with recurrences who experienced severe
      hepatotoxicity while receiving gefitinib and/or erlotinib treatment but could be
      safely switched to afatinib treatment. CONCLUSION: Afatinib could be a well
      tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity,
      which is attributable to its having a different metabolic mechanism compared to
      other EGFR-TKIs.

PMID- 27040073
TI  - The organisational silence of midwives and nurses: reasons and results.
AB  - AIM: The study was conducted to determine the issues about which nurses and
      midwives remain silent and the reasons for it and the perceived results of
      silence. BACKGROUND: Organisational silence is a vitally important issue in the
      health sector, due to the risks and mistakes that are not reported, and proposals
      for improvement that are not made. METHOD: The sample of this descriptive survey,
      which investigated a cause and effect relationship, was 159 nurses and midwives.
      The data were collected using a questionnaire and the organisational silence
      scale. FINDINGS: Of the study participants, 84.9% were nurses and 15.1% were
      midwives. Of all participants 88.7% were women. 8.8% of participants stated that
      they never remained silent about issues related to work and the workplace.
      Respondents most often remained silent about issues related to ethics and
      responsibility. 'Limited improvement and development' was frequently mentioned as
      a perceived result of organisational silence. CONCLUSION: Our study determined
      that organisational silence is quite common among nurses and midwives.
      IMPLICATIONS FOR NURSING MANAGEMENT: Activities that raise the awareness of
      hospital administrations and employees about preventing the factors that cause
      and maintain silence in hospitals should be planned.

PMID- 27040074
TI  - Ethics in the communicative encounter: seriously ill patients' experiences of
      health professionals' nonverbal communication.
AB  - BACKGROUND: The communicative encounter has been described as a fundamental
      element in caring for the patients, and further, in this encounter, the nonverbal
      body language and the tone of speech are agued to play a crucial role. AIM: This
      study explores how seriously ill hospitalised patients experience and assign
      meaning to the health professionals' communication with special attention to the
      nonverbal body language and tone of speech. The study is part of a larger study
      exploring how seriously ill patients experience and assign meaning to the sensory
      impressions in the physical hospital environment as well as to the health
      professionals' communication. METHOD: The study is based on qualitative
      interviews supplemented by observations and applies Paul Ricoeur's
      phenomenological-hermeneutic theory of interpretation in processing the collected
      data. We included twelve patients with potentially life-threatening illnesses
      such as cancer, severe lung, liver and heart disease. FINDINGS: Through analysis
      and interpretation of the interviews, we identified two themes in the text: (i)
      Being confirmed, (ii) Being ignored and an inconvenience. The patients
      experienced that the health professionals' nonverbal communication was imperative
      for their experience of being confirmed or in contrast, their experience of being
      ignored and an inconvenience. CONCLUSION: The health professionals' nonverbal
      communication proved essential for the seriously ill patients' experience of well
      being in the form of positive thoughts and emotions. Consequently, this sensory
      dimension of the communicative encounter represents a significant ethical element
      in caring for the patients.

PMID- 27040075
TI  - BitterX: a tool for understanding bitter taste in humans.
AB  - BitterX is an open-access tool aimed at providing a platform for identifying
      human bitter taste receptors, TAS2Rs, for small molecules. It predicts TAS2Rs
      from the molecular structures of arbitrary chemicals by integrating two
      individual functionalities: bitterant verification and TAS2R recognition. Using
      BitterX, several novel bitterants and their receptors were predicted and
      experimentally validated in the study. Therefore, BitterX may be an effective
      method for deciphering bitter taste coding and could be a useful tool for both
      basic bitter research in academia and new bitterant discoveries in the industry. 

PMID- 27040076
TI  - Prediction of a native ferroelectric metal.
AB  - Over 50 years ago, Anderson and Blount discussed symmetry-allowed polar
      distortions in metals, spawning the idea that a material might be simultaneously
      metallic and ferroelectric. While many studies have ever since considered such or
      similar situations, actual ferroelectricity--that is, the existence of a
      switchable intrinsic electric polarization--has not yet been attained in a metal,
      and is in fact generally deemed incompatible with the screening by mobile
      conduction charges. Here we refute this common wisdom and show, by means of first
      principles simulations, that native metallicity and ferroelectricity coexist in
      the layered perovskite Bi5Ti5O17. We show that, despite being a metal, Bi5Ti5O17
      can sustain a sizable potential drop along the polar direction, as needed to
      reverse its polarization by an external bias. We also reveal striking behaviours,
      as the self-screening mechanism at work in thin Bi5Ti5O17 layers, emerging from
      the interplay between polar distortions and carriers in this compound.

PMID- 27040078
TI  - Diastereomeric resolution directed towards chirality determination focussing on
      gas-phase energetics of coordinated sodium dissociation.
AB  - Defining chiral centres is addressed by introducing a pair of chiral auxiliary
      groups. Ions of diastereomeric pairs of molecules could be distinguished
      utilising energy-resolved mass spectrometry, and the applicability of the method
      to a series of compounds carrying amine, carboxylic acid, alcohol, and all the
      amino acids was verified. The method was further strengthened by distinguishing
      diastereomeric ions that did not undergo fragmentation. Mass spectrometric
      evaluation of the dissociation process of adducted sodium cations from the
      diastereomeric precursors agreed with the theoretical calculations, indicating
      the potential usefulness of the method for the determination of absolute
      configurations. 

PMID- 27040077
TI  - Conformational heterogeneity of the calmodulin binding interface.
AB  - Calmodulin (CaM) is a ubiquitous Ca(2+) sensor and a crucial signalling hub in
      many pathways aberrantly activated in disease. However, the mechanistic basis of
      its ability to bind diverse signalling molecules including G-protein-coupled
      receptors, ion channels and kinases remains poorly understood. Here we harness
      the high resolution of molecular dynamics simulations and the analytical power of
      Markov state models to dissect the molecular underpinnings of CaM binding
      diversity. Our computational model indicates that in the absence of Ca(2+), sub
      states in the folded ensemble of CaM's C-terminal domain present chemically and
      sterically distinct topologies that may facilitate conformational selection.
      Furthermore, we find that local unfolding is off-pathway for the exchange process
      relevant for peptide binding, in contrast to prior hypotheses that unfolding
      might account for binding diversity. Finally, our model predicts a novel binding
      interface that is well-populated in the Ca(2+)-bound regime and, thus, a
      candidate for pharmacological intervention. 

PMID- 27040079
TI  - Sub-5 nm graphene nanopore fabrication by nitrogen ion etching induced by a low
      energy electron beam.
AB  - A flexible and efficient method to fabricate nanopores in graphene has been
      developed. A focused, low-energy (5 keV) electron beam was used to locally
      activate etching of a graphene surface in a low pressure (0.3 Pa) N2 environment.
      Nanopores with sub-5 nm diameters were fabricated. The lattice structure of the
      graphene was observed to recover within 20 nm of the nanopore edge. Nanopore
      growth rates were investigated systematically. The effects of nitrogen pressure,
      electron beam dwell time and beam current were characterised in order to
      understand the etching mechanism and enable optimisation of the etching
      parameters. A model was developed which describes how the diffusion of ionised
      nitrogen affects the nanopore growth rate. Etching of other two-dimensional
      materials was attempted as demonstrated with MoS2. The lack of etching observed
      supports our model of a chemical reaction-based mechanism. The understanding of
      the etching mechanism will allow more materials to be etched by selection of an
      appropriate ion species. 

PMID- 27040080
TI  - Direct C-C coupling of two Ni-salphen complexes to yield dinickel-disalphen
      complexes with symmetric and non-symmetric substitution-patterns.
AB  - The synthesis of symmetric and non-symmetric 5,5'-linked disalophen Ni(ii)
      complexes by the Suzuki-Miyaura-reaction is reported. Also, the synthesis and
      structural characterization of four Ni(ii)-precursor complexes are presented. The
      5-Br-substituted mononuclear complexes and are coupled to the pinacolborane
      substituted complexes and yielding the four dinuclear dinickel complexes in good
      yields. The crystal structure of dinuclear complex was obtained revealing a
      coplanar arrangement between the two salophen fragments. Electronic spectra as
      well as DFT-calculations on the ground states and excitation energies are
      reported and they reveal a small coupling between the electronically saturated Ni
      salophen complexes.

PMID- 27040081
TI  - CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T
      cell receptor sequencing.
AB  - Rasmussen encephalitis (RE) is a rare paediatric epilepsy with uni-hemispheric
      inflammation and progressive neurological deficits. To elucidate RE
      immunopathology, we applied T-cell receptor (TCR) sequencing to blood (n=23),
      cerebrospinal fluid (n=2) and brain biopsies (n=5) of RE patients, and paediatric
      controls. RE patients present with peripheral CD8(+) T-cell expansion and its
      strength correlates with disease severity. In addition, RE is the only paediatric
      epilepsy with prominent T-cell expansions in the CNS. Consistently, common clones
      are shared between RE patients, who also share MHC-I alleles. Public RE clones
      share Vbeta genes and length of the CDR3. Rituximab/natalizumab/basiliximab
      treatment does not change TCR diversity, stem cell transplantation replaces the
      TCR repertoire with minimal overlap between donor and recipient, as observed in
      individual cases. Our study supports the hypothesis of an antigen-specific attack
      of peripherally expanded CD8(+) lymphocytes against CNS structures in RE, which
      might be ameliorated by restricting access to the CNS. 

PMID- 27040082
TI  - Fasting heat production of Saanen and Anglo Nubian goats measured using open
      circuit facemask respirometry.
AB  - This study aimed to establish the heat production (HP) of Saanen and Anglo Nubian
      goats at absorptive (feeding) and at post-absorptive (fasting) statuses to
      determine the adequate period of fasting required for the measurement of basal
      metabolism. Gas exchange was recorded via open-circuit facemask respirometry. Six
      non-lactating and non-pregnant goats of each breed, Saanen (49.2 +/- 3.2 kg of
      body weight, BW) and Anglo Nubian (64.0 +/- 3.0 kg BW), were placed in individual
      pens with ad libitum access to the same total mixed ration. After a 3-day feeding
      period, the animals were subjected to fasting (no feed), and the gas exchange
      measurement was performed for 30 min at 0, 12, 20, 36, 44, 60 and 68 h after
      fasting. The daily HP of the Saanen and Anglo Nubian goats averaged 557.4 +/-
      38.7 and 357.1 +/- 35.3 kJ/kg0.75  BW day respectively. During fasting, the
      methane production decreased exponentially in both breeds, and the critical time
      when methane production was statistically equal to zero was at 31 h of fasting
      for the Saanen goats and at 40 h for the Anglo Nubian goats. The daily HP and
      respiratory exchange rate during fasting decreased up to 60 h. Taken together,
      our results suggest that the ideal period to measure fasting heat production
      (FHP) for goats fed at maintenance levels should be between 40 h and 60 h of
      fasting. Consequently, the daily FHP, after 60 h of fasting, of Saanen and Anglo
      Nubian goats was 183.3 +/- 16.3 and 211.1 +/- 11.5 kJ/kg0.75  BW day
      respectively. The results presented herein are relevant for future studies of
      energy metabolism in goats.

PMID- 27040084
TI  - Reply.

PMID- 27040083
TI  - Comparative transcriptome analyses of seven anurans reveal functions and
      adaptations of amphibian skin.
AB  - Animal skin, which is the tissue that directly contacts the external
      surroundings, has evolved diverse functions to adapt to various environments.
      Amphibians represent the transitional taxon from aquatic to terrestrial life.
      Exploring the molecular basis of their skin function and adaptation is important
      to understand the survival and evolutionary mechanisms of vertebrates. However,
      comprehensive studies on the molecular mechanisms of skin functions in amphibians
      are scarce. In this study, we sequenced the skin transcriptomes of seven anurans
      belonging to three families and compared the similarities and differences in
      expressed genes and proteins. Unigenes and pathways related to basic biological
      processes and special functions, such as defense, immunity, and respiration, were
      enriched in functional annotations. A total of 108 antimicrobial peptides were
      identified. The highly expressed genes were similar in species of the same family
      but were different among families. Additionally, the positively selected
      orthologous groups were involved in biosynthesis, metabolism, immunity, and
      defense processes. This study is the first to generate extensive transcriptome
      data for the skin of seven anurans and provides unigenes and pathway candidates
      for further studies on amphibian skin function and adaptation. 

PMID- 27040085
TI  - Challenging the 4- to 5-minute rule: from perimortem cesarean to resuscitative
      hysterotomy.

PMID- 27040086
TI  - A Systematic Review of the Prevalence and Outcomes of Ideal Cardiovascular Health
      in US and Non-US Populations.
AB  - Several population-based studies have examined the prevalence and trends of the
      American Heart Association's ideal cardiovascular health (CVH) metrics as well as
      its association with cardiovascular disease (CVD)-related morbidity and mortality
      and with non-CVD outcomes. However, no efforts have been made to aggregate these
      studies. Accordingly, we conducted a systematic review to synthesize available
      data on the distribution and outcomes associated with ideal CVH metrics in both
      US and non-US populations. We conducted a systematic search of relevant studies
      in the MEDLINE and CINAHL databases, as well as the Cochrane Register of
      Controlled Trials (CENTRAL). Search terms used included "life's simple 7", "AHA
      2020" and "ideal cardiovascular health". We included articles published in
      English Language from January 1, 2010, to July 31, 2015. Of the 14 US cohorts,
      the prevalence of 6 to 7 ideal CVH metrics ranged from as low as 0.5% in a
      population of African Americans to 12% in workers in a South Florida health care
      organization. Outside the United States, the lowest prevalence was found in an
      Iranian study (0.3%) and the highest was found in a large Chinese corporation
      (15%). All 6 mortality studies reported a graded inverse association between the
      increasing number of ideal CVH metrics and the all-cause and CVD-related
      mortality risk. A similar relationship between ideal CVH metrics and incident
      cardiovascular events was found in 12 of 13 studies. Finally, an increasing
      number of ideal CVH metrics was associated with a lower prevalence and incidence
      of non-CVD outcomes such as cancer, depression, and cognitive impairment. The
      distribution of ideal CVH metrics in US and non-US populations is similar, with
      low proportions of persons achieving 6 or more ideal CVH metrics. Considering the
      strong association of CVH metrics with both CVD and non-CVD outcomes, a
      coordinated global effort for improving CVH should be considered a priority.

PMID- 27040087
TI  - Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle
      Wasting in Patients With Heart Failure With Testosterone Deficiency.
AB  - OBJECTIVE: To examine whether combined testosterone replacement and exercise
      training (ET) therapies would potentiate the beneficial effects of isolated
      therapies on neurovascular control and muscle wasting in patients with heart
      failure (HF) with testosterone deficiency. PATIENTS AND METHODS: From January 10,
      2010, through July 25, 2013, 39 male patients with HF, New York Heart Association
      functional class III, total testosterone level less than 249 ng/dL (to convert to
      nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L
      were randomized to training (4-month cycloergometer training), testosterone
      (intramuscular injection of testosterone undecylate for 4 months), and training +
      testosterone groups. Muscle sympathetic nerve activity was measured using
      microneurography, forearm blood flow using plethysmography, body composition
      using dual X-ray absorptiometry, and functional capacity using cardiopulmonary
      test. Skeletal muscle biopsy was performed in the vastus lateralis. RESULTS:
      Muscle sympathetic nerve activity decreased in ET groups (training, P<.01;
      training + testosterone, P<.01), whereas no changes were observed in the
      testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean
      mass increased in ET groups (training, P<.01; training + testosterone, P<.01),
      whereas lean mass decreased in the testosterone group (P<.01). The response of
      cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in
      the training + testosterone group as compared with the isolated testosterone
      group. CONCLUSION: Our findings provide evidence for a superior effect of
      combined ET and testosterone replacement therapies on muscle sympathetic nerve
      activity, muscle wasting, and functional capacity in patients with HF with
      testosterone deficiency.

PMID- 27040088
TI  - Effects of the main extraction parameters on chemical and microbial
      characteristics of compost tea.
AB  - The rising popularity of compost tea as fertilizer or foliar spray against
      pathogens has encouraged many researchers to evaluate its performance without
      standardizing its quality, so obtaining inconsistent and controversial results.
      The fertilizing and pesticide-like effects of compost tea are due to its chemical
      and microbiological properties. Therefore, this study aimed to identify the best
      combination of the compost tea extraction parameters for exalting both chemical
      and microbiological features. A factorial design was adopted to evaluate the
      effects of compost/water ratio, extraction time, storage duration and storage
      temperature in different combination on physical, chemical and microbiological
      characteristics of compost tea, and the results were elaborated through different
      statistical analyses. Compost tea nutrients and microorganisms were influenced by
      compost/water ratio and extraction time. In addition, the storage duration
      affected the microbial populations, whereas the storage temperature influenced
      only the fungal population of compost tea. Results suggested that the best
      combination of the studied parameters was: 1:2.5 compost/water ratio, 2days of
      extraction time and the compost tea should be utilized immediately after the
      extraction, since the storage reduced the microbial populations. 

PMID- 27040089
TI  - Effects of phosphoric acid sprayed into an incinerator furnace on the flue gas
      pressure drop at fabric filters.
AB  - Fabric filters are widely used to remove dust from flue gas generated by waste
      incineration. However, a pressure drop occurs at the filters, caused by growth of
      a dust layer on the filter fabric despite regular cleaning by pulsed-jet air. The
      pressure drop at the fabric filters leads to energy consumption at induced draft
      fan to keep the incinerator on negative pressure, so that its proper control is
      important to operate incineration facility efficiently. The pressure drop at
      fabric filters decreased whenever phosphoric acid wastewater (PAW) was sprayed
      into an incinerator for treating industrial waste. Operational data obtained from
      the incineration facility were analyzed to determine the short- and long-term
      effects of PAW spraying on the pressure drop. For the short-term effect, it was
      confirmed that the pressure drop at the fabric filters always decreased to 0.3
      1.2kPa within about 5h after spraying PAW. This effect was expected to be
      obtained by about one third of present PAW spraying amount. However, from the
      long-term perspective, the pressure drop showed an increase in the periods of PAW
      spraying compared with periods for which PAW spraying was not performed. The
      pressure drop increase was particularly noticeable after the initial PAW
      spraying, regardless of the age and type of fabric filters used. These results
      suggest that present PAW spraying causes a temporary pressure drop reduction,
      leading to short-term energy consumption savings; however, it also causes an
      increase of the pressure drop over the long-term, degrading the overall operating
      conditions. Thus, appropriate PAW spraying conditions are needed to make
      effective use of PAW to reduce the pressure drop at fabric filters from a short-
      and long-term point of view. 

PMID- 27040090
TI  - Lactic acid fermentation from food waste with indigenous microbiota: Effects of
      pH, temperature and high OLR.
AB  - The effects of pH, temperature and high organic loading rate (OLR) on lactic acid
      production from food waste without extra inoculum addition were investigated in
      this study. Using batch experiments, the results showed that although the
      hydrolysis rate increased with pH adjustment, the lactic acid concentration and
      productivity were highest at pH 6. High temperatures were suitable for
      solubilization but seriously restricted the acidification processes. The highest
      lactic acid yield (0.46g/g-TS) and productivity (278.1mg/Lh) were obtained at 37
      degrees C and pH 6. In addition, the lactic acid concentration gradually
      increased with the increase in OLR, and the semi-continuous reactor could be
      stably operated at an OLR of 18g-TS/Ld. However, system instability, low lactic
      acid yield and a decrease in VS removal were noticed at high OLRs (22g-TS/Ld).
      The concentrations of volatile fatty acids (VFAs) in the fermentation mixture
      were relatively low but slightly increased with OLR, and acetate was the
      predominant VFA component. Using high-throughput pyrosequencing, Lactobacillus
      from the raw food waste was found to selectively accumulate and become dominant
      in the semi-continuous reactor. 

PMID- 27040091
TI  - Combined oxidative leaching and electrowinning process for mercury recovery from
      spent fluorescent lamps.
AB  - In this paper, oxidative leaching and electrowinnig processes were performed to
      recovery of mercury from spent tubular fluorescent lamps. Hypochlorite was found
      to be effectively used for the leaching of mercury to the solution. Mercury could
      be leached with an efficiency of 96% using 0.5M/0.2M NaOCl/NaCl reagents at 50
      degrees C and pH 7.5 for 2-h. Electrowinning process was conducted on the
      filtered leaching solutions and over the 81% of mercury was recovered at the
      graphite electrode using citric acid as a reducing agent. The optimal process
      conditions were observed as a 6A current intensity, 30g/L of reducing agent
      concentration, 120min. electrolysis time and pH of 7 at the room temperature. It
      was found that current intensity and citric acid amount had positive effect for
      mercury reduction. Recovery of mercury in its elemental form was confirmed by
      SEM/EDX. Oxidative leaching with NaOCl/NaCl reagent was followed by
      electrowinning process can be effectively used for the recovery of mercury from
      spent fluorescent lamps.

PMID- 27040092
TI  - Histochemical study of the olfactory mucosae of the horse.
AB  - The olfactory mucosae of the horse were examined by using histology and lectin
      histochemistry to characterize the carbohydrate sugar residues therein.
      Histological findings revealed that olfactory epithelium (OE) consisted of both
      olfactory marker protein (OMP)- and protein gene product (PGP) 9.5-positive
      receptor cells, supporting cells and basal cells with intervening secretory ducts
      from Bowman's glands. Mucus histochemistry showed that Bowman's gland acini
      contain periodic acid-Schiff (PAS) reagent-positive neutral mucins and alcian
      blue pH 2.5-positive mucosubstances. Lectin histochemistry revealed that a
      variety of carbohydrate sugar residues, including N-acetylglucosamine, mannose,
      galactose, N-acetylgalactosamine, fucose and complex type N-glycan groups, are
      present in the various cell types in the olfactory mucosa at varying levels.
      Collectively, this is the first descriptive study of horse olfactory mucosa to
      characterize carbohydrate sugar residues in the OE and Bowman's glands. 

PMID- 27040093
TI  - Corrigendum to "Development of a new measure for assessing insight: Psychometric
      properties of the insight orientation scale (IOS)" [Schizophr. Res. 169 (2015)
      298-302].

PMID- 27040094
TI  - Autologous lipografting to reconstruct the labia majora following vulvectomy.

PMID- 27040095
TI  - Applying Atherosclerotic Risk Prevention Guidelines to Elderly Patients: A Bridge
      Too Far?
AB  - The primary prevention of atherosclerotic disease is on the basis of optimal
      management of the major risk factors. For the major risk factors of diabetes,
      hypertension, and dyslipidemia, management for most patients is on the basis of
      well developed and extensive evidence-based diagnostic and therapeutic
      guidelines. However, for a growing segment of the population who are at the
      highest risk for atherosclerotic disease (ie, older adults), the application of
      these guidelines is problematic. First, few studies that form the evidence base
      for these primary prevention guidelines actually include substantial numbers of
      elderly subjects. Second, elderly patients represent a special population from
      multiple perspectives related to their accumulation of health deficits and in
      their development of frailty. These patients with frailty and multiple
      comorbidities have been mostly excluded from the primary prevention studies upon
      which the guidelines are based yet comprise a very significant proportion of the
      very elderly population. Third, elderly people are at most risk from adverse drug
      reactions because of the increasing number of medications prescribed in this
      patient population. When applying the existing guidelines to elderly people the
      limitations of our knowledge must be recognized regarding how best to mitigate
      the high risk of heart disease in our aging population and how to generalize
      these recommendations to the management of the largest subgroup of elderly
      patients (ie, those with multiple comorbidities and frail older adults). 

PMID- 27040096
TI  - Cellular Senescence and Vascular Disease: Novel Routes to Better Understanding
      and Therapy.
AB  - Cellular senescence is a definable fate of cells within aging, diseased, and
      remodelling tissues. The traditional hallmark of cellular senescence is permanent
      cell cycle arrest but the senescent state is also accompanied by secretion of
      proteins that can reinforce the senescent phenotype and adversely affect the
      local tissue environment. Assessment for cellular markers of senescence has
      revealed the existence of senescent smooth muscle cells and senescent endothelial
      cells in vessels of patients with atherosclerosis and hypertension. This raises
      the possibility that cellular senescence might contribute to the initiation or
      progression of vascular disease. Potential disease-promoting pathways include
      blunted replicative reserve, reduced nitric oxide production, and increased
      cellular stiffness. Moreover, the secretory phenotype of senescent vascular cells
      might promote vascular degeneration through chronic inflammation and
      extracellular matrix degradation. Slowing of vascular cell aging and selective
      clearing of cells that have become senescent are emerging as exciting
      possibilities for controlling vascular disease.

PMID- 27040097
TI  - Vascular Aging: Lessons From Pediatric Hypertension.
AB  - Hypertension (HTN) in children is associated with early vascular aging (EVA) and
      underlying immunologic-metabolic abnormalities and accelerated biological
      maturation. Morphologic and functional vascular changes underlying EVA and HTN in
      children resemble those seen in the elderly including but not limited to an
      increase in intima-media thickness (IMT) and arterial stiffness and endothelial
      dysfunction. Although progeria syndrome leading to EVA and the development of
      clinically manifested cardiovascular (CV) disease in the second decade of life is
      a rare hereditary disorder, primary HTN, which is also associated with EVA, is
      much more common (reported in up to 10% in adolescents). EVA associated with HTN
      in children leads to the premature development of target organ injury in
      childhood and CV events in early adulthood. Limited evidence from prospective
      observational studies in children and adolescents indicates that early lifestyle
      measures (low salt/low sugar intake and exercise) or pharmacologic treatment of
      HTN, or both, partially reverses morphologic and functional changes underlying
      EVA such as an increase in carotid IMT and pulse wave velocity, a decrease in
      flow-mediated dilation of the brachial artery, and an increase in oxidative
      stress and visceral fat. Future mechanistic and therapeutic clinical trials are
      desirable to assess the mechanisms and treatment strategies of EVA in the context
      of HTN in children and their effect on CV events in early adulthood.

PMID- 27040098
TI  - Protective effects of resveratrol on aging-induced cognitive impairment in rats.
AB  - Resveratrol, a polyphenol phytoalexine, has been shown to play a neuroprotective
      role in the neurodegenerative process in Alzheimer's disease (AD) and improve
      memory function in dementia. However, the in vivo effect of resveratrol in normal
      aging models of learning and memory has not yet been evaluated. Therefore, the
      present neurobehavioral study was undertaken to evaluate the effect of
      resveratrol on cognitive impairment induced by aging in passive avoidance and
      Morris water maze (MWM) tests. Male Wistar albino rats were divided into four
      groups: young control (4month), young resveratrol (4month+RESV), old control
      (24month) and old resveratrol (24month+RESV). Resveratrol (50mg/kg/day) was given
      to the 4month+RESV and 24month+RESV groups orally for 12weeks. There was no
      significant difference between the groups for the first day of latency, while in
      aged rats, the second day of latency was significantly shortened compared to the
      young group in the passive avoidance test (p<0.05). Additionally, in the MWM
      test, the results showed a decrease in the time spent in the escape platform's
      quadrant in the probe test in aged rats (p<0.05). The administration of
      resveratrol at 50mg/kg/day increased the retention scores in the passive
      avoidance test and the time spent in the escape platform's quadrant in the MWM
      task (p<0.05). Furthermore resveratrol attenuated the protein levels of TNFalpha
      and IL1beta in the 24-month group. These findings indicate that aging impairs
      emotional and spatial learning-memory and resveratrol reverses the effect of age
      related learning and memory impairment. The results of this study suggest that
      resveratrol is effective in preventing cognitive deficit in aged rats by
      inhibiting the production of inflammatory cytokines.

PMID- 27040099
TI  - Feasibility of nonradiation EUS-based ERCP in patients with uncomplicated
      choledocholithiasis (with video).
AB  - BACKGROUND AND AIMS: ERCP inherently involves radiation exposure. Nonradiation
      ERCP has been described in pregnancy. Theoretically, the same techniques could be
      applied to the general population. We prospectively assessed the feasibility of
      nonradiation, EUS-based ERCP in nonpregnant patients with choledocholithiasis.
      METHODS: Consecutive patients referred for ERCP for choledocholithiasis were
      recruited over a 1-year period. Patients providing study consent underwent the
      following procedural protocol. First, EUS was performed to verify the presence,
      size, and number of stones. Second, biliary cannulation was attempted without
      fluoroscopy for a maximum of 10 minutes. Selective cannulation was based on deep
      insertion with visible bile in the catheter on aspiration. Third, for stone
      removal, sphincterotomy was performed and stones were removed using a basket or
      balloon. The number of stones exiting the papilla was matched to the number seen
      on EUS. Finally, once the duct was deemed clear by the endoscopist, a final
      occlusion cholangiogram and ductal sweep served as the reference standard for
      confirmation of stone clearance. RESULTS: Nonradiation ERCP was attempted in 31
      patients. Cannulation without fluoroscopy was successful in 26 patients (84%).
      Complete stone removal without fluoroscopy was achieved in all 26 of these cases.
      The 5 patients with failed nonfluoroscopic cannulation required double guidewire
      (n = 2) or precut papillotomy (n = 3) for deep biliary access and subsequent
      stone clearance. One patient who required precut papillotomy for access developed
      moderate post-ERCP pancreatitis (3%). CONCLUSIONS: Nonradiation, EUS-based ERCP
      for uncomplicated choledocholithiasis appears to be successful and safe.
      (Clinical trial registration number: NCT01678391.).

PMID- 27040100
TI  - [A chronic rhinorrhea].

PMID- 27040101
TI  - The transition to non-lead rifle ammunition in Denmark: National obligations and
      policy considerations.
AB  - The issue of Denmark regulating use of lead-free rifle ammunition because of
      potential risks of lead exposure in wildlife and humans was examined from a
      scientific and objective policy perspective. The consequences of adopting or
      rejecting such regulation were identified. Denmark is obliged to examine this
      topic because of its national policy on lead reduction, its being a Party to the
      UN Bonn Convention on Migratory Species, and its role in protecting White-tailed
      Sea Eagles (Haliaeetus albicilla), a species prone to lead poisoning from lead
      ingestion. Lead-free bullets suited for deer hunting are available at comparable
      cost to lead bullets, and have been demonstrated to be as effective. National
      adoption of lead-free bullets would complete the Danish transition to lead-free
      ammunition use. It would reduce the risk of lead exposure to scavenging wildlife,
      and humans who might eat lead-contaminated wild game meat. Opposition from
      hunting organizations would be expected. 

PMID- 27040102
TI  - The standard of care of patients with ARDS: ventilatory settings and rescue
      therapies for refractory hypoxemia.
AB  - PURPOSE: Severe ARDS is often associated with refractory hypoxemia, and early
      identification and treatment of hypoxemia is mandatory. For the management of
      severe ARDS ventilator settings, positioning therapy, infection control, and
      supportive measures are essential to improve survival. METHODS AND RESULTS: A
      precise definition of life-threating hypoxemia is not identified. Typical
      clinical determinations are: arterial partial pressure of oxygen < 60 mmHg and/or
      arterial oxygenation < 88 % and/or the ratio of PaO2/FIO2 < 100. For mechanical
      ventilation specific settings are recommended: limitation of tidal volume (6
      ml/kg predicted body weight), adequate high PEEP (>12 cmH2O), a recruitment
      manoeuvre in special situations, and a 'balanced' respiratory rate (20-30/min).
      Individual bedside methods to guide PEEP/recruitment (e.g., transpulmonary
      pressure) are not (yet) available. Prone positioning [early (<= 48 hrs after
      onset of severe ARDS) and prolonged (repetition of 16-hr-sessions)] improves
      survival. An advanced infection management/control includes early diagnosis of
      bacterial, atypical, viral and fungal specimen (blood culture, bronchoalveolar
      lavage), and of infection sources by CT scan, followed by administration of broad
      spectrum anti-infectives. Neuromuscular blockage (Cisatracurium <= 48 hrs after
      onset of ARDS), as well as an adequate sedation strategy (score guided) is an
      important supportive therapy. A negative fluid balance is associated with
      improved lung function and the use of hemofiltration might be indicated for
      specific indications. CONCLUSIONS: A specific standard of care is required for
      the management of severe ARDS with refractory hypoxemia.

PMID- 27040103
TI  - Personalized medicine for ARDS: the 2035 research agenda.
AB  - In the last 20 years, survival among patients with acute respiratory distress
      syndrome (ARDS) has increased substantially with advances in lung-protective
      ventilation and resuscitation. Building on this success, personalizing mechanical
      ventilation to patient-specific physiology for enhanced lung protection will be a
      top research priority for the years ahead. However, the ARDS research agenda must
      be broader in scope. Further understanding of the heterogeneous biology, from
      molecular to mechanical, underlying early ARDS pathogenesis is essential to
      inform therapeutic discovery and tailor treatment and prevention strategies to
      the individual patient. The ARDSne(x)t research agenda for the next 20 years
      calls for bringing personalized medicine to ARDS, asking simultaneously both
      whether a treatment affords clinically meaningful benefit and for whom. This
      expanded scope necessitates standard acquisition of highly granular biological,
      physiological, and clinical data across studies to identify biologically distinct
      subgroups that may respond differently to a given intervention. Clinical trials
      will need to consider enrichment strategies and incorporate long-term functional
      outcomes. Tremendous investment in research infrastructure and global
      collaboration will be vital to fulfilling this agenda. 

PMID- 27040105
TI  - Unintentional epidural placement of a thoracic paravertebral catheter inserted
      using an ultrasound-guided technique: a case report.
AB  - This is the first case report describing the epidural misplacement of an infusion
      catheter, which was intended to be located in the thoracic paravertebral space
      using an ultrasound-guided technique. The patient was a 57-year-old female
      undergoing a laparoscopy-assisted left partial nephrectomy. Before surgery, a
      Tuohy needle was inserted into the paravertebral space at the left ninth
      intercostal space using an in-plane transverse ultrasound-guided approach in the
      lateral-to-medial direction. A catheter was then threaded into the paravertebral
      space through the needle. Subsequently, the catheter position was secured,
      although ultrasound-guided confirmation of air injected through the catheter into
      the paravertebral space was not obtained. Twenty milliliters of 0.5 %
      levobupivacaine was administered through the catheter at both the initiation and
      conclusion of surgery. A neurologic examination following surgery revealed
      paraplegia, along with sensory deficits in the bilateral T3-S5 dermatome. The
      motor dysfunction in the lower extremities lasted 7 h, and the sensory block
      lasted 13.5 h. Postoperative radiologic confirmation of the catheter position
      concomitant with the spread of radiopaque dye revealed that the tip of the
      catheter was lying in the epidural space. Unless precise attention is paid to
      detection of the catheter tip location, a thoracic paravertebral catheter can
      enter into the epidural space even under ultrasound guidance.

PMID- 27040104
TI  - The Role of Trunk Musculature in Osteoporotic Vertebral Fractures: Implications
      for Prediction, Prevention, and Management.
AB  - This review examines the current evidence for associations between vertebral
      fractures (VFx), the most common type of fracture in older adults, and trunk
      muscles, which are intimately tied to spinal loading and function. Individuals
      with prevalent VFxs have more fat infiltration in the trunk muscles, lower trunk
      extension strength, and altered muscle activation patterns. However, no
      longitudinal studies have examined whether assessment of trunk muscle can
      contribute to prediction of fracture risk. A few studies report that exercise
      interventions targeting the trunk muscles can reduce the risk of VFx, improve
      trunk strength and endurance in patients who have had a VFx, and reduce the risk
      of falling, a common cause of VFx, but the quality of evidence is low. Trunk
      muscles likely have an important role to play in prediction, prevention, and
      management of VFx, but additional longitudinal studies and randomized controlled
      trials are needed to clarify this role.

PMID- 27040106
TI  - Principled Missing Data Treatments.
AB  - We review a number of issues regarding missing data treatments for intervention
      and prevention researchers. Many of the common missing data practices in
      prevention research are still, unfortunately, ill-advised (e.g., use of listwise
      and pairwise deletion, insufficient use of auxiliary variables). Our goal is to
      promote better practice in the handling of missing data. We review the current
      state of missing data methodology and recent missing data reporting in prevention
      research. We describe antiquated, ad hoc missing data treatments and discuss
      their limitations. We discuss two modern, principled missing data treatments:
      multiple imputation and full information maximum likelihood, and we offer
      practical tips on how to best employ these methods in prevention research. The
      principled missing data treatments that we discuss are couched in terms of how
      they improve causal and statistical inference in the prevention sciences. Our
      recommendations are firmly grounded in missing data theory and well-validated
      statistical principles for handling the missing data issues that are ubiquitous
      in biosocial and prevention research. We augment our broad survey of missing data
      analysis with references to more exhaustive resources.

PMID- 27040107
TI  - Vitamin D Deficiency and Critical Illness: Correspondence.

PMID- 27040108
TI  - Vitamin D Deficiency and Critical Illness: Author's Reply.

PMID- 27040109
TI  - Sex differences in the radial grooves in the first extensor compartment.
AB  - OBJECTIVE: De Quervain tenosynovitis affects the first extensor compartment of
      the wrist and occurs more frequently in females. This high prevalence could not
      be explained by soft tissue. As the osseous anatomy has been mostly neglected, we
      aimed to compare the distal radius between the sexes. MATERIALS AND METHODS: We
      evaluated the presence of a bony ridge on the floor of the first extensor
      compartment on CT images with multiplanar imaging. RESULTS: We included 244
      wrists (72 females, 172 males) in the study. A bony ridge was present in 58 (23.8
      %) and absent in 186 (76.2 %) wrists. A ridge was present in 24 (33.3 %) wrists
      among females and 34 (19.8 %) wrists among males. A groove with a bony ridge was
      statistically associated with females. CONCLUSION: We observed two tendon groove
      morphologies for the first extensor compartment. A groove with a bony ridge
      occurs more frequently in females. Further research is needed to clarify the
      relationship between the high frequency of a bony ridge and increased prevalence
      of de Quervain tenosynovitis in females.

PMID- 27040110
TI  - Sensitive spectrophotometric determination of Co(II) using dispersive liquid
      liquid micro-extraction method in soil samples.
AB  - Analytical performance of conventional spectrophotometer was developed by
      coupling of effective dispersive liquid-liquid micro-extraction method with
      spectrophotometric determination for ultra-trace determination of cobalt. The
      method was based on the formation of Co(II)-alpha-benzoin oxime complex and its
      extraction using a dispersive liquid-liquid micro-extraction technique. During
      the present work, several important variables such as pH, ligand concentration,
      amount and type of dispersive, and extracting solvent were optimized. It was
      found that the crucial factor for the Co(II)-alpha benzoin oxime complex
      formation is the pH of the alkaline alcoholic medium. Under the optimized
      condition, the calibration graph was linear in the ranges of 1.0-110 MUg L(-1)
      with the detection limit (S/N = 3) of 0.5 MUg L(-1). The preconcentration
      operation of 25 mL of sample gave enhancement factor of 75. The proposed method
      was applied for determination of Co(II) in soil samples.

PMID- 27040111
TI  - Bilateral nephromegaly due to isolated renal sarcoidosis.

PMID- 27040112
TI  - Human Beige Adipocytes: Epiphenomenon or Drivers of Metabolic Improvements?
AB  - There is a lack of direct evidence that human brown or beige adipocytes improve
      whole-body energy homeostasis. In a recent study, Min et al. implanted
      proliferated human adipocyte progenitors from a 3D culture system in mice.
      Implants responded to adipogenic stimuli and had a beige-like phenotype upon
      induction that significantly improved systemic metabolic parameters.

PMID- 27040113
TI  - A duplex real-time PCR assay based on TaqMan technology for simultaneous
      detection and differentiation of canine adenovirus types 1 and 2.
AB  - Canine adenoviruses are a major cause of disease in dogs, coyotes, red foxes and
      wolves, as well as in other carnivores and marine mammals. Canine adenovirus type
      1 (CAdV-1) and canine adenovirus type 2 (CAdV-2) cause infectious canine
      hepatitis (ICH) and infectious tracheobronchitis (ITB), respectively. In this
      study, a duplex real-time PCR assay for simultaneous detection and
      characterisation of CAdV-1 and CAdV-2 was developed by using a single primer pair
      and virus-specific probes. The assay was validated testing standard DNAs produced
      on purpose and clinical samples of various matrices known to be positive for CAdV
      1, CAdV-2 or both viruses. Precise calculation of DNA loads in samples containing
      a wide range of viral amounts was allowed by generating a standard curve for
      absolute quantification. The assay was proven to be highly specific, since no
      cross-reactions with the different CAdV type was observed, and sensitive, being
      able to detect less than 10 copies of CAdV-1/CAdV-2 DNA. The low intra-assay and
      interassay coefficient of variations demonstrated a high repeatability, thus
      confirming the potential use of this assay for quantitative detection of CAdV-1
      and CAdV-2 for rapid diagnosis and epidemiological investigations.

PMID- 27040115
TI  - Improvement of left ventricular filling by ivabradine during chronic
      hypertension: involvement of contraction-relaxation coupling.
AB  - Chronic hypertension is associated with left ventricular (LV) hypertrophy and LV
      diastolic dysfunction with impaired isovolumic relaxation and abnormal LV
      filling. Increased heart rate (HR) worsens these alterations. We investigated
      whether the I f channel blocker ivabradine exerts beneficial effects on LV
      filling dynamic. In this setting, we also evaluated the relationship between LV
      filling and isovolumic contraction as a consequence of contraction-relaxation
      coupling. Therefore, hypertension was induced by a continuous infusion of
      angiotensin II during 28 days in 10 chronically instrumented pigs. LV function
      was investigated after stopping angiotensin II infusion to offset the changes in
      loading conditions. In the normal heart, LV relaxation filling, LV early filling,
      LV peak early filling rate were positively correlated to HR. In contrast, these
      parameters were significantly reduced at day 28 vs. day 0 (18, 42, and 26 %,
      respectively) despite the increase in HR (108 +/- 6 beats/min vs. 73 +/- 2
      beats/min, respectively). These abnormalities were corrected by acute
      administration of ivabradine (1 mg/kg, iv). Ivabradine still exerted these
      effects when HR was controlled at 150 beats/min by atrial pacing. Interestingly,
      LV relaxation filling, LV early filling and LV peak early filling were strongly
      correlated with both isovolumic contraction and relaxation. In conclusion,
      ivabradine improves LV filling during chronic hypertension. The mechanism
      involves LV contraction-relaxation coupling through normalization of isovolumic
      contraction and relaxation as well as HR-independent mechanisms.

PMID- 27040116
TI  - Application of supervised machine learning algorithms for the classification of
      regulatory RNA riboswitches.
AB  - Riboswitches, the small structured RNA elements, were discovered about a decade
      ago. It has been the subject of intense interest to identify riboswitches,
      understand their mechanisms of action and use them in genetic engineering. The
      accumulation of genome and transcriptome sequence data and comparative genomics
      provide unprecedented opportunities to identify riboswitches in the genome. In
      the present study, we have evaluated the following six machine learning
      algorithms for their efficiency to classify riboswitches: J48, BayesNet, Naive
      Bayes, Multilayer Perceptron, sequential minimal optimization, hidden Markov
      model (HMM). For determining effective classifier, the algorithms were compared
      on the statistical measures of specificity, sensitivity, accuracy, F-measure and
      receiver operating characteristic (ROC) plot analysis. The classifier Multilayer
      Perceptron achieved the best performance, with the highest specificity,
      sensitivity, F-score and accuracy, and with the largest area under the ROC curve,
      whereas HMM was the poorest performer. At present, the available tools for the
      prediction and classification of riboswitches are based on covariance model,
      support vector machine and HMM. The present study determines Multilayer
      Perceptron as a better classifier for the genome-wide riboswitch searches.

PMID- 27040114
TI  - Impaired coronary metabolic dilation in the metabolic syndrome is linked to
      mitochondrial dysfunction and mitochondrial DNA damage.
AB  - Mitochondrial dysfunction in obesity and diabetes can be caused by excessive
      production of free radicals, which can damage mitochondrial DNA. Because
      mitochondrial DNA plays a key role in the production of ATP necessary for cardiac
      work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial
      DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood
      flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese
      fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and
      arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented
      coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial
      respiration was impaired and ROS production was greater in ZOF than ZLN. These
      were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if
      coronary metabolic dilation, the hyperemic response induced by heightened cardiac
      metabolism, is linked to mitochondrial function we introduced recombinant
      proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or
      repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial
      function and metabolic dilation, and reduced ROS production in ZOF; whereas
      induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS
      production, and attenuated metabolic dilation. Adequate metabolic dilation was
      also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac
      myocytes; whereas myocytes from rats with impaired dilation released only H2O2.
      In conclusion, our results suggest that mitochondrial function plays a seminal
      role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is
      central to this process.

PMID- 27040117
TI  - Resistance against Echinostoma caproni (Trematoda) secondary infections in mice
      is not dependent on the ileal protein production.
AB  - Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode,
      which has been widely employed to investigate the factors determining the
      rejection of intestinal helminths. Protein production patterns of intestinal
      epithelial cells are related to the infection-induced changes that determine the
      course of E. caproni infections. Herein, we compare the protein production
      profiles in the ileum of four experimental groups of mice: control; infected;
      dewormed and reinfected. Worm burdens were significantly lower in secondary
      infections, confirming the generation of partial resistance to homologous
      secondary infections in mice. However, quantitative comparison by 2D-DIGE showed
      that the protein production profile is similar in control and dewormed mice, and
      after primary and secondary E. caproni infections. These results showed that,
      unexpectedly, protein production changes in E. caproni infections are not
      responsible of resistance development. Fifty-one protein spots were
      differentially produced between control/treated and infected/reinfected mice and
      37 of them were identified by mass spectrometry. The analysis of differentially
      abundant proteins indicate that cell metabolism and the regulation of
      proliferation and cell death are the most affected processes after primary and
      secondary E. caproni infections. These results provide new insights into the
      proteins involved in the regulation of tissue homeostasis after intestinal
      infection. SIGNIFICANCE: Intestinal helminthiases are highly prevalent parasitic
      infections with about 1 billion people infected worldwide. In this scenario,
      better understanding of host-parasite relationships is needed to elucidate the
      factors that determine intestinal helminth rejection. The intestinal trematode
      Echinostoma caproni has been broadly employed in this field, with resistance
      against secondary homologous infections reported in mice. In this paper, new
      insights are provided in the regulation of tissue homeostasis after intestinal
      infection. The unexpected lack of an altered pattern of ileal protein production
      associated to resistance development suggests that this resistance depends on
      rapid changes, affecting the early establishment of worms, rather than the
      activation of later effector mechanisms. These results may contribute to the
      development of new control tools for the management of these parasitic
      infections.

PMID- 27040118
TI  - How should a bio-mathematical model be used within a fatigue risk management
      system to determine whether or not a working time arrangement is safe?
AB  - Bio-mathematical models that predict fatigue and/or sleepiness have proved a
      useful adjunct in the management of what has been typically referred to as
      fatigue-related risk. Codifying what constitutes appropriate use of these models
      will be increasingly important over the next decade. Current guidelines for
      determining a safe working time arrangement based on model outputs generally use
      a single upper threshold and are, arguably, over-simplistic. These guidelines
      fail to incorporate explicitly essential aspects of the risk assessment process -
      namely, the inherent uncertainty and variability in human sleep-wake behavior;
      the non-linear relationship between fatigue, task performance and safety
      outcomes; the consequence of a fatigue-related error and its influence on overall
      risk; and the impact of risk mitigation or controls in reducing the likelihood or
      consequence of a fatigue-related error. As industry and regulatory bodies
      increasingly move toward performance-based approaches to safety management, any
      fatigue risk management system that includes a bio-mathematical model should
      specify what exactly is measured by the model, and how the model can be used in
      the context of a safety management system approach. This will require significant
      dialog between the various parties with an interest in bio-mathematical models,
      i.e. developers, vendors, end-users, and regulators.

PMID- 27040120
TI  - Organic-Inorganic Perovskites: Structural Versatility for Functional Materials
      Design.
AB  - Although known since the late 19th century, organic-inorganic perovskites have
      recently received extraordinary research community attention because of their
      unique physical properties, which make them promising candidates for application
      in photovoltaic (PV) and related optoelectronic devices. This review will explore
      beyond the current focus on three-dimensional (3-D) lead(II) halide perovskites,
      to highlight the great chemical flexibility and outstanding potential of the
      broader class of 3-D and lower dimensional organic-based perovskite family for
      electronic, optical, and energy-based applications as well as fundamental
      research. The concept of a multifunctional organic-inorganic hybrid, in which the
      organic and inorganic structural components provide intentional, unique, and
      hopefully synergistic features to the compound, represents an important
      contemporary target. 

PMID- 27040121
TI  - Quantitative Subtractively Normalized Interfacial Fourier Transform Infrared
      Reflection Spectroscopy Study of the Adsorption of Adenine on Au(111) Electrodes.
AB  - Quantitative subtractively normalized interfacial Fourier transform infrared
      reflection spectroscopy (SNIFTIRS) was used to determine the molecular
      orientation and identify the metal-molecular interactions responsible for the
      adsorption of adenine from the bulk electrolyte solution onto the surface of the
      Au(111) electrode. The recorded p-polarized IR spectra of the adsorbed species
      were subtracted from the collected s-polarized IR spectra to remove the IR
      contributions of the vibrational bands of the desorbed molecules that are located
      within the thin layer cavity of the spectroelectrochemical cell. The intense IR
      band around 1640 cm(-1), which is assigned to the pyrimidine ring stretching
      vibrations of the C5-C6 and C6-N10 bonds, and the IR band at 1380 cm(-1), which
      results from a combination of the ring stretching vibration of the C5-C7 bond and
      the in-plane CH bending vibration, were selected for the quantitative analysis
      measurements. The transition dipoles of these bands were evaluated by DFT
      calculations. Their orientations differed by 85 +/- 5 degrees . The tilt angles
      of adsorbed adenine molecules were calculated from the intensity of these two
      vibrations at different potentials. The results indicate that the molecular plane
      is tilted at an angle of 40 degrees  with respect to the surface normal of the
      electrode and rotates by 16 degrees  around its normal axis with increasing
      electrode potential. This orientation results from the chemical interaction
      between the N10 and gold atoms coupled with the pi-pi parallel stacking
      interactions between the adjacent adsorbed molecules. Furthermore, the changes in
      the molecular plane rotation with the electric field suggests that the N1 atom of
      adenine must also participate in the interaction between the molecule and metal.

PMID- 27040123
TI  - Switchable Dry Adhesion with Step-like Micropillars and Controllable Interfacial
      Contact.
AB  - Dry adhesives have attracted much attention because of their repeatable and
      reversible attachment. Many research groups have made fruitful achievements in
      fabricating and designing various dry adhesives. However, most of these studies
      focus on imitating bioinspired geometry to achieve this smart adhesion,
      neglecting the contact interface control through their peeling motion. Here, we
      present an alternative design to achieve this switchable adhesion on the basis of
      controlling contact areas. This unique design includes micropillars array with
      large overhanging caps and a "step" located at the center line of the cap. When
      dragging the pillars in the direction of the upper surface of the step, the lower
      surface is brought into contact, rapidly yielding stronger adhesion (switched-on
      state). Alternatively, when dragging the pillars in the direction of the lower
      surface of the step, the contact areas decrease sharply, leading to weak adhesion
      (switched-off state). Such switchable property under strong adhesion force is
      exactly what many practical applications need, and the ability to achieve this
      property by controlling the adhesion area size presented here opens a new way to
      dry adhesives design. 

PMID- 27040122
TI  - Inflammatory markers are associated with decreased psychomotor speed in patients
      with major depressive disorder.
AB  - Previous data have demonstrated that administration of inflammatory cytokines or
      their inducers leads to altered basal ganglia function associated with reduced
      psychomotor speed. Decreased psychomotor speed, referred to clinically as
      psychomotor retardation, is a cardinal symptom of major depressive disorder (MDD)
      and has been associated with poor antidepressant treatment response. We therefore
      examined the association between plasma inflammatory markers and psychomotor
      speed in ninety-three un-medicated patients with MDD. Psychomotor speed was
      assessed by a range of neuropsychological tests from purely motor tasks (e.g.
      movement latency and finger tapping) to those that involved motor activity with
      increasing cognitive demand and cortical participation (e.g. Trails A and Digit
      Symbol Substitution Task (DSST)). Linear regression analyses were performed to
      determine the relationship of inflammatory markers and psychomotor task
      performance controlling for age, race, sex, education, body mass index, and
      severity of depression. MDD patients exhibited decreased psychomotor speed on all
      tasks relative to normative standards. Increased IL-6 was associated with
      decreased performance on simple and choice movement time tasks, whereas MCP-1 was
      associated with decreased performance on the finger tapping task and DSST. IL-10
      was associated with increased performance on the DSST. In an exploratory
      principle component analysis including all psychomotor tasks, IL-6 was associated
      with the psychomotor speed factor. Taken together, the data indicate that a
      peripheral inflammatory profile including increased IL-6 and MCP-1 is
      consistently associated with psychomotor speed in MDD. These data are consistent
      with data demonstrating that inflammation can affect basal ganglia function, and
      indicate that psychomotor speed may be a viable outcome variable for anti
      inflammatory therapies in depression and other neuropsychiatric disorders with
      increased inflammation. 

PMID- 27040124
TI  - Improving Hand Hygiene Practices in a Rural Hospital in Sub-Saharan Africa.
AB  - OBJECTIVE To improve hand hygiene (HH) compliance among physicians and nurses in
      a rural hospital in sub-Saharan Africa (SSA) using the World Health
      Organization's (WHO's) Guidelines on Hand Hygiene in Health Care. DESIGN This
      study was a quasi-experimental design divided into 4 phases: (1) preparation of
      materials and acquisition of the hospital administration's support, (2) baseline
      evaluation, (3) intervention, and (4) follow-up evaluation. SETTING A 160-bed,
      non-referral hospital in Gitwe, Rwanda PARTICIPANTS A total of 12 physicians and
      54 nurses participated in this study. METHODS The intervention consisted of
      introducing locally produced alcohol-based hand rub (ABHR); educating healthcare
      workers (HCWs) on proper HH practice; providing pocket-sized ABHR bottles for
      HCWs; placing HH reminders in the workplace; and surveying HCWs at surrounding
      health centers regarding HH compliance barriers. Hand hygiene infrastructure,
      compliance, and knowledge were assessed among physicians and nurses using
      baseline observations and a follow-up evaluation survey. RESULTS Overall, HH
      compliance improved from 34.1% at baseline to 68.9% post intervention (P.05).
      CONCLUSION Hand hygiene campaigns using WHO methods in SSA have been implemented
      exclusively in large, referral hospitals. This study shows that an HH program
      using the WHO tools successfully improved HH in a low-income, rural hospital in
      SSA. Infect Control Hosp Epidemiol 2016;37:834-839.

PMID- 27040125
TI  - Structuring Roles and Gender Identities Within Families Explaining Suicidal
      Behavior in South India.
AB  - BACKGROUND: This paper examines the social structures, culture, gendered roles,
      and their implications for suicidal behavior in South India. Exploring the
      cultural process within the structures of family and society to understand
      suicide and attempted suicide from the perspectives of survivors, mental health
      professionals, and traditional healers has not been achieved in the existing
      suicide-related research studies conducted in India to date. AIMS: This study
      aimed to explore the cultural implications of attempted suicide by examining the
      survivors' life stories, their perceptions, and service providers'
      interpretations of problem situation. METHOD: A qualitative design was used
      drawing on constant comparison method and thematic analysis. The analysis was
      underpinned by the theoretical concepts of Bourdieu's work. In-depth interviews
      were conducted with 15 survivors of attempted suicide, eight mental health
      professionals, and eight traditional healers from Southern India. RESULTS: The
      study found interactions among visible and invisible fields such as faith, power,
      control, culture, family, religion, and social systems to have strengthened the
      disparities in gender and role structures within families and societies and to
      have impacted survivors' dispositions to situations. CONCLUSION: The role of
      culture in causing suicide and attempted suicide is explained by unraveling the
      negative impact of interacting cultural and structural mechanisms.

PMID- 27040126
TI  - Bullying, Depression, and Suicide Risk in a Pediatric Primary Care Sample.
AB  - BACKGROUND: Suicide is a serious public health concern for US youth. Research has
      established an association between bullying and suicide risk. However, several
      questions remain regarding this relationship. AIMS: The present study examined
      (a) whether experiences of verbal, physical, and cyber bullying were uniquely
      associated with general suicide risk; (b) whether each specific form of bullying
      was related to suicide attempt; and (c) whether depression moderated the
      relationship between each type of bullying and suicide risk. METHOD: The sample
      included medical records of 5,429 youth screened in primary care when providers
      had mental health concerns. Patients were screened using the Behavioral Health
      Screen (BHS), which assessed a range of mental health problems and behaviors,
      including bullying, depression, and suicide. RESULTS: All types of bullying were
      associated with suicide risk, but verbal bullying was uniquely associated with
      suicide attempt. Depression significantly moderated the relationship between each
      type of bullying and suicide risk. CONCLUSION: The study's limitations include
      the use of cross-sectional and self-data reports. When medical providers evaluate
      suicide risk, bullying should be considered as a possible precipitant, especially
      if the patient is depressed. Verbal bullying may be particularly important in
      understanding severity of suicide risk.

PMID- 27040127
TI  - The Response in Twitter to an Assisted Suicide in a Television Soap Opera.
AB  - BACKGROUND: Concern has been expressed about the potentially contagious effect of
      television soap opera suicides and suicidal language in social media. AIMS:
      Twitter content was analyzed during the week in which a fictional assisted
      suicide was broadcast on a British television soap opera, "Coronation Street."
      METHOD: Tweets were collected if they contained language indicating possible
      suicidal intent or used the word suicide. The modified Thompson tau method was
      used to test for any differences in the volume of tweets in both categories on
      the day of screening. Content analysis broke down the use of the word suicide
      into six thematic categories. RESULTS: There was no evidence on the day of
      screening of an increase in tweets expressing possible suicidal intent but there
      was an increase in tweets containing the word suicide. Content analysis found the
      most common thematic category to be information or support, followed by the
      raising of moral issues in relation to suicide. CONCLUSION: It is possible that
      for certain high-profile media events Twitter may be used more as a civic
      reactive forum than as a medium for introspection or disclosure of distress.

PMID- 27040128
TI  - Risky Integration.
AB  - BACKGROUND: Although the protective value of social connectedness is emphasized
      in suicide prevention programming, little is known about the relationship between
      connectedness in high-risk runaway and homeless youth (RHY) networks and suicidal
      ideation. AIMS: The study examined how social connectedness, in the form of
      social network position and network exposures, was associated with suicidal
      ideation among RHY. METHOD: Using population-level social network data from 384
      RHY, each youth's network position and exposure to potentially suicidogenic peer
      attributes were calculated. Logistic regression analyses were used to examine
      associations between network position (core vs. periphery), peer exposures (e.g.,
      depressed or suicidal peers), and suicidal ideation. RESULTS: In univariable
      analyses, being in the core of the network and being connected to greater
      proportions of depressed and suicidal peers increased the likelihood of suicidal
      ideation. In the final multivariable model, higher exposure to depressed peers
      remained associated with suicidal ideation, and a marginal effect for network
      position was observed. CONCLUSION: The risk of suicidal ideation was linked to
      depression among peers and to a lesser extent being more integrated into the RHY
      network. Identifying and treating depression in naturally occurring friendship
      groups, particularly in the core of the network, represents a promising network
      level intervention.

PMID- 27040129
TI  - Police and Suicide Prevention.
AB  - BACKGROUND: Police officers are frequently the first responders to individuals in
      crisis, but generally receive little training for this role. We developed and
      evaluated training in suicide awareness and prevention for frontline rail police
      in the UK. AIMS: To investigate the impact of training on officers' suicide
      prevention attitudes, confidence, and knowledge. METHOD: Fifty-three participants
      completed a brief questionnaire before and after undertaking training. In
      addition, two focus groups were conducted with 10 officers to explore in greater
      depth their views and experiences of the training program and the perceived
      impact on practice. RESULTS: Baseline levels of suicide prevention attitudes,
      confidence, and knowledge were mixed but mostly positive and improved
      significantly after training. Such improvements were seemingly maintained over
      time, but there was insufficient power to test this statistically. Feedback on
      the course was generally excellent, notwithstanding some criticisms and
      suggestions for improvement. CONCLUSION: Training in suicide prevention appears
      to have been well received and to have had a beneficial impact on officers'
      attitudes, confidence, and knowledge. Further research is needed to assess its
      longer-term effects on police attitudes, skills, and interactions with suicidal
      individuals, and to establish its relative effectiveness in the context of
      multilevel interventions.

PMID- 27040130
TI  - Substance Use as a Mediator of the Association Between Demographics, Suicide
      Attempt History, and Future Suicide Attempts in Emergency Department Patients.
AB  - BACKGROUND: Identification of factors that predict and protect against attempted
      suicide are critical for the development of effective suicide prevention and
      intervention programs. AIMS: To examine whether substance use mediates the
      association between demographic characteristics, suicide attempt history, and
      reports of a suicide attempt within 12 months after screening positive for active
      suicidal ideation or behavior during the index emergency department (ED) visit.
      METHOD: Data were collected during the first two phases of the Emergency
      Department Safety Assessment and Follow-up Evaluation (ED-SAFE) study. Data
      collection included baseline interview; 6- and 12-month chart reviews; and 6-, 12
      , 24-, 36-, and 52-week telephone follow-up assessments. Structural equation
      modeling was used. All p values were two-tailed, with p < .05 considered
      statistically significant. RESULTS: Among the 874 subjects, 195 (22%) reported a
      suicide attempt within 12 months after the index ED visit. Of participants
      reporting a suicide attempt, 59% were < 40 years old, 59% female, and 76% non
      Hispanic White. Associations between race, sex, and suicide attempt 12 months
      after the index ED visit may be mediated by a combination of alcohol misuse and
      cocaine use. CONCLUSION: Findings from the mediation analyses provide insight
      into the impact of substance use on future suicide attempts in various
      sociodemographic groups.

PMID- 27040131
TI  - Effects of sodium butyrate supplementation on reproductive performance and
      colostrum composition in gilts.
AB  - Nutrients are essential for the health and survival of human beings and animals.
      Also, they play a major role in enhancing reproductive efficiency. The aim of the
      current study was to investigate the effects of sodium butyrate (SB) on
      reproductive performance and colostrum composition in gilts. A total of 40 Large
      White*Landrace replacement gilts (at the age of 160 to 175 days) were fed either
      a standard diet (control group, n=20) or standard diet top dressed with
      encapsulated SB at the level of 500 mg/kg (SB group, n=20) from 1 month before
      mating to 7 days after farrowing. The rate of gilts regular return to estrus
      after insemination was lower in SB group than the control group. The total number
      of piglets born (P=0.179) and the litter weight at birth (P=0.063) did not differ
      between the two treatment groups. However, the mean BW at day 7 tended to be
      greater in SB group (P=0.051) and average daily gain of piglets was greater
      (P=0.011) compared with control group. Colostrum samples were collected at
      parturition and the concentrations of total protein (P=0.197), cholesterol
      (P=0.161) and lactose (P=0.923) were not influenced by SB supplementation.
      However, compared with control gilts, colostrum from SB-treated gilts contained
      lower triglyceride (P=0.050). Moreover, colostrum concentrations of prolactin
      (P=0.005) and leptin (P=0.006) were significantly lower in SB group. No
      significant differences were noted for the colostral concentrations of cortisol
      (P=0.899), thyroxine (P=0.891) or triiodothyronine (P=0.194). The concentration
      of lipopolysaccharide in colostrum was not influenced by SB supplementation
      (P=0.972). However, colostrum from SB-treated gilts had significantly lower tumor
      necrosis factor alpha (TNFalpha) (P=0.030) and higher immunoglobulin A (IgA)
      (P=0.042). Collectively, SB supplementation could reduce the rate of gilts return
      to estrus, alter the composition of colostrum and enhance the growth rate of
      piglets. Moreover, SB could alter the immune function of newborn piglets through
      decreased production of TNFalpha and increased IgA concentration in colostrum. 

PMID- 27040133
TI  - Variable levels of apoptotic signal-associated cytokines in the disease course of
      patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.
AB  - BACKGROUND/OBJECTIVES: Keratinocyte death is a hallmark of Stevens-Johnson
      syndrome and toxic epidermal necrolysis (SJS/TEN). Apoptotic signal-associated
      cytokines, such as TNF-alpha, sFasL, granulysin, sTRAIL and IFN-gamma have been
      reported to participate in keratinocyte apoptosis. However, their levels are
      variable, which hampers the elucidation of the role of these cytokines. We sought
      to determine whether cytokine levels vary with disease course. METHODS: The serum
      cytokine levels of 24 patients and blister fluid of 10 were analysed by enzyme
      linked immunosorbent assay on the first day of their admission to hospital and
      were evaluated at different time points in the disease course. Meanwhile, surface
      markers (CD3, CD4, CD8, CD1a, CD14, CD16+56 and CD68) of blister fluid cells were
      measured by flow cytometry. RESULTS: The concentrations of all cytokines in the
      serum and blister fluid were higher than those in the controls and were more
      elevated in the blister fluid than in the serum. Moreover, sTRAIL, IFN-gamma and
      TNF-alpha quantities were relatively stable, while those of sFasL and granulysin
      decreased rapidly in the disease course. On the first day, CD8+ T and natural
      killer cells were predominant in the blister fluid but their relative percentage
      diminished gradually, while that of CD14+ cells increased. CONCLUSION: Our study
      confirmed there are high but variable levels of these cytokines in SJS/TEN,
      especially in the early phase and different tendencies are manifested in the
      disease course.

PMID- 27040134
TI  - Free will perceptions and psychiatric symptoms in patients diagnosed with
      schizophrenia.
AB  - WHAT IS KNOWN ON THE SUBJECT?: Some research suggests that holding a free will
      perspective may offer mental health and physical health benefits. WHAT THIS PAPER
      ADDS TO EXISTING KNOWLEDGE?: This study is the first to examine links between
      free will perceptions and psychiatric symptoms in patients diagnosed with
      schizophrenia. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Study results suggest
      that helping people with a diagnosis of schizophrenia to recognize situations
      where they do have some freedom of choice over their actions and emotional
      reactions (free will) may assist them in improving their experiences and better
      managing their symptoms. ABSTRACT: Introduction Some research indicates that
      having a strong sense that one possesses free will may be associated with better
      psychological and physical health. This study is the first to examine the
      relationship between free will perceptions and psychiatric symptoms in patients
      with a diagnosis of schizophrenia. Method Thirty-two participants were
      interviewed using the Brief Psychiatric Rating Scale to assess symptom severity
      and the Free Will Subscale of the Free Will and Determinism Scale to assess free
      will perceptions. Results As hypothesized, a negative association was found
      between free will perceptions and total symptom severity, though it appears that
      this was mainly accounted for by positive symptoms. A content analysis was also
      conducted to qualitatively examine how patients conceptualize the construct of
      free will and its role in coping with their own mental illness. Discussion Study
      results suggest that holding a free will perspective may mitigate psychiatric
      symptoms in patients with a diagnosis of schizophrenia. Thus, psychiatric nurses
      and other mental health clinicians may improve current treatments for
      schizophrenia by helping patients recognize situations where they do have some
      freedom of choice over their actions and emotional reactions (free will) to
      stressful life events.

PMID- 27040135
TI  - E1 detection as prognosticator in human papillomavirus-positive head and neck
      cancers.
AB  - PURPOSE: HPV-related locally advanced head and neck cancers (LA-HNCs) show a good
      prognosis. This study aimed to investigate the HPV prevalence in LA-HNCs and
      compare the prognostic value of E1, E6 and L1 genomic viral fragments and p16,
      individually and in combination, in order to find the best prognosticator in
      terms of overall survival (OS) and progression-free survival (PFS). PATIENTS AND
      METHODS: HPV16 was searched in 255 LA-HNC formalin-fixed paraffin-embedded tumor
      tissues, 89 oropharyngeal cancers (OPCs), and 166 non-OPCs by DNA-PCR with 3
      primer pairs. p16 was analyzed by immunohistochemistry in 235 patients. RESULTS:
      The prevalence of positive samples decreased constantly from E6 to L1 and E1 in
      both OPCs and non-OPCs. Each LA-HNC patient highlighted variable positivity for
      each fragment. OPCs showed a higher prevalence of positive samples compared to
      non-OPCs.Positive coexistence of all the fragments was more common in OPCs
      (31.5%) than non-OPCs (4.2%), and E1 detection was always associated with E6 and
      L1. E1-positive OPCs showed improved OS (p = 0.012) and PFS (p = 0.036), while L1
      or E6-positive ones did not. p16-positive patients were more prevalent in the
      OPC (29.8%) than the non-OPC group (7.3%) (p<0.0001) and its prognostic value was
      not superior to that of E1. However, the multivariate Cox analysis which included
      E1, L1, E6 status and p16 expression did not show a significant p value.
      CONCLUSIONS: Though HPV16 positivity measured by DNA-PCR was higher for L1 and
      E6, they performed weakly as prognosticators; E1 might become a strong prognostic
      marker for OS and PFS in OPCs.

PMID- 27040136
TI  - Thermal-activated nanocarriers for the manipulation of cellular uptake and
      photothermal therapy on command.
AB  - Smart nanocarriers with switchable surfaces consisting of thermo-sensitive
      polymers and aptamers have been developed, through which the cellular uptake and
      photothermal therapy in five different cells could be spatial-temporally
      controlled on command, which is beneficial in maximizing therapy efficacy and
      minimizing side effects. 

PMID- 27040137
TI  - Diaper Dermatitis: A Review of 63 Children.
AB  - BACKGROUND/OBJECTIVE: Diaper dermatitis (DD) is a common infantile dermatosis
      with a highly variable prevalence and incidence. This study aimed to present the
      demographic and clinical features of babies with DD. METHODS: Data, including
      demographic and clinical features, obtained from DD patient forms were
      retrospectively analyzed. RESULTS: The study included 63 babies with DD (female:
      n = 35 [55.6%]; male: n = 28 [44.4%]; mean age 11.6 mos). Most of the patients
      (43.5%) were 0 to 6 months of age. In all, 76.3% were breastfed, of whom 31.7%
      were exclusively breastfed. The number of previous episodes of DD was
      significantly lower in breastfed babies. The most common diaper area cleansing
      method was wet wipes (54.1%). Diaper creams were used in 86.2% of patients. DD
      was severe in 22.2% of patients, moderate in 57.4%, and mild in 20.4%. Candida
      infection was noted in 77.4% of patients. The median number of previous episodes
      of DD was significantly higher in patients with Candida infection than in those
      without (p = 0.02). Treatment yielded greater than 50% improvement (complete and
      moderate response) in 59.4% of patients at the first follow-up visit (3-5 days)
      and 82.6% at the second follow-up visit (10 days). CONCLUSION: Most babies with
      DD were 0 to 6 months of age. Breastfed babies had fewer previous episodes of DD,
      so mothers should be encouraged to breastfeed their babies to reduce the
      incidence of DD. Candida infection was common; clinicians should be aware of its
      association with DD.

PMID- 27040138
TI  - Editorial (Thematic Issue: Neuroprotective Effects of Li - It is Elementary).

PMID- 27040139
TI  - An Anti-apoE4 Specific Monoclonal Antibody Counteracts the Pathological Effects
      of apoE4 In Vivo.
AB  - ApolipoproteinE4 (apoE4) is the most prevalent genetic risk factor for
      Alzheimer's disease (AD) and as such is a promising therapeutic target. This
      study examined the extent to which the pathological effects of apoE4 can be
      counteracted in vivo utilizing an immunological approach in which anti-apoE4
      antibodies are applied peripherally by i.p. injections into apoE4-targeted
      replacement mice. Prerequisites for the successful pursuit of this objective are
      the availability of antibodies that specifically bind brain apoE4 and not apoE3,
      and demonstrating that direct application of these antibodies into the brain can
      counteract the effects of apoE4. Accordingly, it was shown that the antiapoE4
      monoclonal antibody (mAb) 9D11 binds specifically to brain apoE4 and not apoE3.
      Direct i.c.v. application of mAb 9D11 prevented the apoE4-driven accumulation of
      Abeta in hippocampal neurons following activation of the amyloid cascade by
      inhibiting the Abeta-degrading enzyme neprilysin. These findings provide a proof
      of-concept that anti-apoE4 mAb 9D11, when introduced into the brain, can
      counteract the apoE4 effects in vivo. Subsequent experiments, utilizing repeated
      i.p. injections of mAb 9D11, resulted in the formation of apoE/IgG complexes
      specifically in apoE4 mice. This was associated with reversal of the cognitive
      impairments of apoE4 in the Morris water maze and the novel object recognition
      test as well as with reversal of key apoE4-driven pathologies including the
      hyperphosphorylated tau and the reduced levels of the apoER2 receptor. These
      results indicate that anti-apoE4 immunotherapy counteracts the cognitive and
      brain pathological effects of apoE4, and suggest that such an approach could also
      benefit human apoE4 carriers.

PMID- 27040140
TI  - Butyrylcholinesterase as a Diagnostic and Therapeutic Target for Alzheimer's
      Disease.
AB  - The serine hydrolase butyrylcholinesterase (BChE), like the related enzyme
      acetylcholinesterase (AChE), co-regulates metabolism of the neurotransmitter
      acetylcholine. In the human brain BChE is mainly expressed in white matter and
      glia and in distinct populations of neurons in regions that are important in
      cognition and behavior, functions compromised in Alzheimer's disease (AD). AD is
      a neurodegenerative disorder causing dementia with no cure nor means for
      definitive diagnosis during life. In AD, BChE is found in association with
      pathology, such as beta-amyloid (Abeta) plaques, particularly in the cerebral
      cortex where BChE is not normally found in quantity. Up to 30% of cognitively
      normal older adults have abundant Abeta deposition in the brain. We have designed
      an imaging agent that can detect, through autoradiography, BChE-associated Abeta
      plaques in the cerebral cortex of AD brains, but does not visualize Abeta plaques
      in brains of cognitively normal individuals. Furthermore, in an AD mouse model
      with BChE gene knocked out, there are up to 70% fewer fibrillar Abeta brain
      plaques, suggesting diminished BChE activity could prove beneficial as a curative
      approach to AD. To that end, we have examined numerous N-10-carbonyl
      phenothiazines that are specific inhibitors of human BChE, revealing important
      details of the enzyme's active site gorge. These phenothiazines can be designed
      without potential side effects caused by neurotransmitter receptor interactions.
      In conclusion, BChE is potentially an important target for diagnosis and
      treatment of AD.

PMID- 27040141
TI  - Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD
      Mice.
AB  - Apathy is an early and common neuropsychiatric syndrome in Alzheimer's disease
      (AD) patients. In clinical trials, apathy is associated with decreased motor
      activity that can be monitored by actigraphy. The triple transgenic mouse AD
      model (3xTgAD) has been shown to recapitulate the biochemical lesions as well as
      many of the synaptic and cognitive alterations associated with AD. In the present
      work we found that these mice also develop an early and consistent apathy-like
      behavior as evidenced by a drastic decrease in spontaneous activity measured by
      actimetry. We recently established that these mice also display an intraneuronal
      accumulation of the beta-secretase-derived betaAPP fragment (C99) appearing
      early, in absence of Abeta. Interestingly, we found that the apathy-like behavior
      observed in 3xTgAD mice was temporally associated with C99 accumulation and
      synaptic alterations. Since it is well known that the genetic background can
      strongly influence behavior and can induce transcriptional variability in animal
      models, we decided to determine the influence of genetic background on the above
      described alterations. We backcrossed 3xTgAD mice to C57BL/6 and found that the
      genetic background had no influence on either C99 accumulation or synaptic
      plasticity alterations, but strongly affected the apathy-like behavior.

PMID- 27040142
TI  - A novel, optical, on-line bacteria sensor for monitoring drinking water quality.
AB  - Today, microbial drinking water quality is monitored through either time
      consuming laboratory methods or indirect on-line measurements. Results are thus
      either delayed or insufficient to support proactive action. A novel, optical, on
      line bacteria sensor with a 10-minute time resolution has been developed. The
      sensor is based on 3D image recognition, and the obtained pictures are analyzed
      with algorithms considering 59 quantified image parameters. The sensor counts
      individual suspended particles and classifies them as either bacteria or abiotic
      particles. The technology is capable of distinguishing and quantifying bacteria
      and particles in pure and mixed suspensions, and the quantification correlates
      with total bacterial counts. Several field applications have demonstrated that
      the technology can monitor changes in the concentration of bacteria, and is thus
      well suited for rapid detection of critical conditions such as pollution events
      in drinking water. 

PMID- 27040132
TI  - Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease.
AB  - BACKGROUND: Previous trials have shown that the use of statins to lower
      cholesterol reduces the risk of cardiovascular events among persons without
      cardiovascular disease. Those trials have involved persons with elevated lipid
      levels or inflammatory markers and involved mainly white persons. It is unclear
      whether the benefits of statins can be extended to an intermediate-risk,
      ethnically diverse population without cardiovascular disease. METHODS: In one
      comparison from a 2-by-2 factorial trial, we randomly assigned 12,705
      participants in 21 countries who did not have cardiovascular disease and were at
      intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo.
      The first coprimary outcome was the composite of death from cardiovascular
      causes, nonfatal myocardial infarction, or nonfatal stroke, and the second
      coprimary outcome additionally included revascularization, heart failure, and
      resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS: The
      overall mean low-density lipoprotein cholesterol level was 26.5% lower in the
      rosuvastatin group than in the placebo group. The first coprimary outcome
      occurred in 235 participants (3.7%) in the rosuvastatin group and in 304
      participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence
      interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary
      outcome were consistent with the results for the first (occurring in 277
      participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in
      the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The
      results were also consistent in subgroups defined according to cardiovascular
      risk at baseline, lipid level, C-reactive protein level, blood pressure, and race
      or ethnic group. In the rosuvastatin group, there was no excess of diabetes or
      cancers, but there was an excess of cataract surgery (in 3.8% of the
      participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8%
      of the participants, vs. 4.7% in the placebo group; P=0.005). CONCLUSIONS:
      Treatment with rosuvastatin at a dose of 10 mg per day resulted in a
      significantly lower risk of cardiovascular events than placebo in an intermediate
      risk, ethnically diverse population without cardiovascular disease. (Funded by
      the Canadian Institutes of Health Research and AstraZeneca; HOPE-3
      ClinicalTrials.gov number, NCT00468923.).

PMID- 27040143
TI  - Toileting behaviour and related health beliefs among Chinese female nurses.
AB  - AIMS: To investigate the toileting behaviours that female nurses used to empty
      their bladders, health beliefs related to toileting behaviour and the
      relationships between the health beliefs and toileting behaviour based on the
      Health Belief Model. METHODS: A stratified cluster sampling strategy was used to
      recruit 636 female nurses from three tertiary hospitals in China. Reliable and
      valid questionnaires were used to assess female nurses' toileting behaviour and
      health beliefs related to toileting behaviour. The structural equation model was
      applied to explore the relationships between health belief constructs and
      toileting behaviour. RESULTS: The most common unhealthy toileting behaviour was
      that of delayed voiding. More than half of the nurses (53.6%) often or always
      delayed emptying their bladders when they were busy. Approximately one-third of
      female nurses often or always crouched over the toilet to empty their bladders
      when not at home. Nearly two-thirds often or always worried about the cleanliness
      of public toilets. Of all the participants, 67.5% of female nurses had at least
      one type of lower urinary tract symptom (LUTS); however, the majority did not
      believe that they were susceptible to these symptoms. Moreover, they had
      misconceptions that premature voiding would reduce the risk, relieve the symptoms
      and prevent the recurrence of LUTS. CONCLUSIONS: Many female nurses engaged in
      unhealthy toileting behaviours and might not know what types of toileting
      behaviours are healthy. Nurses play an important role in patient education and
      are a major source of health information for society. It is particularly
      important to look more closely at toileting behaviour among nurses and implement
      education and training to promote healthy toileting behaviour and, in turn,
      optimise bladder health.

PMID- 27040145
TI  - Is trabeculectomy really superior to canaloplasty?

PMID- 27040144
TI  - ADAMTS13 autoantibodies cloned from patients with acquired thrombotic
      thrombocytopenic purpura: 1. Structural and functional characterization in vitro.
AB  - BACKGROUND: Acquired thrombotic thrombocytopenia purpura (TTP) is a life
      threatening illness caused by autoantibodies that decrease the activity of
      ADAMTS13, the von Willebrand factor-cleaving protease. Despite efficacy of plasma
      exchange, mortality remains high and relapse is common. Improved therapies may
      come from understanding the diversity of pathogenic autoantibodies on a molecular
      or genetic level. Cloning comprehensive repertoires of patient autoantibodies can
      provide the necessary tools for studying immunobiology of disease and developing
      animal models. STUDY DESIGN AND METHODS: Anti-ADAMTS13 antibodies were cloned
      from four patients with acquired TTP using phage display and characterized with
      respect to genetic origin, inhibition of ADAMTS13 proteolytic activity, and
      epitope specificity. Anti-idiotypic antisera raised to a subset of autoantibodies
      enabled comparison of their relatedness to each other and to polyclonal
      immunoglobulin (Ig)G in patient plasma. RESULTS: Fifty-one unique antibodies were
      isolated comprising epitope specificities resembling the diversity found in
      circulating patient IgG. Antibodies directed both to the amino terminal domains
      and to those requiring the ADAMTS13 cysteine-rich/spacer region for binding
      inhibited proteolytic activity, while those solely targeting carboxy-terminal
      domains were noninhibitory. Anti-idiotypic antisera raised to a subset of
      antibody clones crossreacted with and reduced the inhibitory activity of
      polyclonal IgG from a set of unrelated patients. CONCLUSIONS: Anti-ADAMTS13
      autoantibodies isolated by repertoire cloning display the diversity of epitope
      specificities found in patient plasma and provide tools for developing animal
      models of acquired TTP. Shared idiotypes of inhibitory clones with circulating
      IgG from multiple patients suggest common features of pathogenic autoantibodies
      that could be exploited for developing more targeted therapies.

PMID- 27040146
TI  - Microsatellite markers for the critically endangered elm species Ulmus gaussenii
      (Ulmaceae).
AB  - The Anhui elm Ulmus gaussenii is listed as a critically endangered species by the
      International Union for Conservation of Nature and is endemic to China, where its
      only population is restricted to Langya Mountain in Chuzhou, Anhui Province. To
      better understand the population genetics of U. gaussenii, we developed 12
      microsatellite markers using an improved technique. The 12 markers were
      polymorphic, with the number of alleles per locus ranging from two to nine.
      Observed and expected heterozygosities ranged from 0.021 to 0.750 and 0.225 to
      0.744, respectively. The inbreeding coefficient ranged from -0.157 to 0.960.
      Significant linkage disequilibrium was detected for two pairs of loci, and
      significant deviations from Hardy-Weinberg equilibrium were found in nine loci.
      These microsatellite markers will contribute to the studies of population
      genetics in U. gaussenii, which in turn will contribute to species conservation
      and protection. 

PMID- 27040147
TI  - Identification of reference genes for quantitative expression analysis using
      large-scale RNA-seq data of Arabidopsis thaliana and model crop plants.
AB  - In quantitative gene expression analysis, normalization using a reference gene as
      an internal control is frequently performed for appropriate interpretation of the
      results. Efforts have been devoted to exploring superior novel reference genes
      using microarray transcriptomic data and to evaluating commonly used reference
      genes by targeting analysis. However, because the number of specifically
      detectable genes is totally dependent on probe design in the microarray analysis,
      exploration using microarray data may miss some of the best choices for the
      reference genes. Recently emerging RNA sequencing (RNA-seq) provides an ideal
      resource for comprehensive exploration of reference genes since this method is
      capable of detecting all expressed genes, in principle including even unknown
      genes. We report the results of a comprehensive exploration of reference genes
      using public RNA-seq data from plants such as Arabidopsis thaliana (Arabidopsis),
      Glycine max (soybean), Solanum lycopersicum (tomato) and Oryza sativa (rice). To
      select reference genes suitable for the broadest experimental conditions
      possible, candidates were surveyed by the following four steps: (1) evaluation of
      the basal expression level of each gene in each experiment; (2) evaluation of the
      expression stability of each gene in each experiment; (3) evaluation of the
      expression stability of each gene across the experiments; and (4) selection of
      top-ranked genes, after ranking according to the number of experiments in which
      the gene was expressed stably. Employing this procedure, 13, 10, 12 and 21 top
      candidates for reference genes were proposed in Arabidopsis, soybean, tomato and
      rice, respectively. Microarray expression data confirmed that the expression of
      the proposed reference genes under broad experimental conditions was more stable
      than that of commonly used reference genes. These novel reference genes will be
      useful for analyzing gene expression profiles across experiments carried out
      under various experimental conditions.

PMID- 27040148
TI  - Memoir on the origin of wheat stocks used by Prof. Tetsu Sakamura, on the
      centennial of his discovery of the correct chromosome number and polyploidy in
      wheat.
AB  - Sakamura (1918) reported the discovery of a polyploid series among eight species
      of the genus Triticum; this series consisted of 2x, 4x and 6x species with 2n =
      14, 28 and 42 chromosomes, respectively. He mentioned in this article that all
      the materials he used were gifted by T. Minami of the same department of Hokkaido
      University, Japan. In addition to carrying out an extensive collection of cereal
      germplasms in the period 1914 to 1916, Minami wrote on October 7, 1915 to K. A.
      Flaksberger, a wheat taxonomist at the Bureau of Applied Botany, Saint
      Petersburg, Russia, requesting seeds of Russian wheat and other cereals. He sent
      Flaksberger a letter of acknowledgement for seed stocks on May 19, 1916; thus,
      the requested seed package must have arrived from Flaksberger at some time
      between October 7, 1915 and May 19, 1916. Based on the available documents, there
      was a considerable period of time between these seed stocks reaching Minami and
      Sakamura's publication of the chromosome numbers with the discovery of
      polyploidy. In fact, the wheat species identified by Flaksberger (1915) and those
      studied by Sakamura (1918) were identical except for two wild species which
      appeared only in Flaksberger's list. The available information supports a
      proposal that the wheat species used by Sakamura (1918) in his discovery of
      polyploidy, and later by Kihara (1924, 1930) in his genome analysis, originated
      from Flaksberger's collection. 

PMID- 27040150
TI  - Pharmacotherapies for Retinal Detachment.
AB  - Retinal detachment is an important cause of visual loss. Currently, surgical
      techniques, including vitrectomy, scleral buckle, and pneumatic retinopexy, are
      the only means to repair retinal detachment and restore vision. However, surgical
      failure rates may be as high as 20%, and visual outcomes continue to vary
      secondary to multiple processes, including postoperative cystoid macular edema,
      epiretinal membrane formation, macular folds, and, ultimately, photoreceptor
      death. Therefore, pharmacotherapies are being sought to aid the success rates of
      modern surgical techniques and reduce or slow the degeneration of photoreceptors
      during retinal detachment. This review discusses potential therapeutic avenues
      that aid in retinal reattachment, reduce the rate of retinal redetachment by
      limiting proliferative vitreoretinopathy, and protect against photoreceptor cell
      death.

PMID- 27040149
TI  - Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow
      Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials.
AB  - PURPOSE: To evaluate the association between pseudodrusen and incidence of late
      age-related macular degeneration (AMD) in fellow eyes of patients with unilateral
      neovascular AMD (nAMD). DESIGN: Cohort study within the Comparison of AMD
      Treatments Trials (CATT). PARTICIPANTS: Patients with neither nAMD nor geographic
      atrophy (GA) in the fellow eye at baseline. METHODS: Presence and type (dot,
      reticular, or confluent) of baseline pseudodrusen were assessed using digital
      color fundus photography (CFP) viewed under full color, green channel, and blue
      channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was
      based on monthly clinical examination and reading center evaluation of images at
      years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and
      FA images at years 1 and 2. Associations of baseline pseudodrusen with incident
      nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95%
      confidence intervals (CIs) from multivariate Cox models, with adjustment of
      covariates identified through backward stepwise selection. MAIN OUTCOME MEASURES:
      Incident nAMD and GA. RESULTS: Among 620 fellow eyes, 176 (28.4%) had baseline
      pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD
      occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without
      pseudodrusen (aRR, 2.05; 95% CI, 1.43-2.93); GA occurred in 27 eyes (15.3%) with
      pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13
      3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes
      (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51-2.83). Dot pseudodrusen
      were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60-4.00), whereas
      confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI,
      1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless
      of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7%
      vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%). CONCLUSIONS: In fellow
      eyes of CATT participants, pseudodrusen were associated independently with a
      higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD,
      whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be
      considered along with the AREDS severity score for predicting late AMD.

PMID- 27040151
TI  - Biomimetic Solid-State Nanochannels: From Fundamental Research to Practical
      Applications.
AB  - In recent years, solid-state smart nanopores/nanochannels for intelligent control
      of the transportation of ions and molecules as organisms have been extensively
      studied, because they hold great potential applications in molecular sieves,
      nanofluidics, energy conversion, and biosensors. To keep up with the fast
      development of this field, it is necessary to summarize the construction,
      characterization, and application of biomimetic smart nanopores/nanochannels.
      These can be classified into four sections: the fabrication of solid-state
      nanopores/nanochannels, the functionalization methods and materials, the
      mechanism explanation about the ion rectification, and the practical
      applications. A brief conclusion and outlook for the biomimetic nanochannels is
      provided, highlighting those that could be developed and integrated into devices
      for use in tackling current and the future problems including resources, energy,
      environment, and health. 

PMID- 27040152
TI  - Topical Imiquimod for the Treatment of Childhood Cutaneous Langerhans Cell
      Histiocytosis.
AB  - Although topical steroids are considered first-line treatment for cutaneous
      Langerhans cell histiocytosis (LCH), the appropriate therapy for refractory cases
      remains controversial. We report a 16-month-old girl with isolated cutaneous LCH
      refractory to treatment with topical corticosteroids and topical tacrolimus.
      Treatment was initiated with 5% topical imiquimod cream and the rash completely
      resolved after 5 months of therapy. There was no disease recurrence after more
      than 2 years of follow-up. We present this case to highlight imiquimod as a novel
      therapeutic agent for the management of isolated cutaneous LCH in children.

PMID- 27040153
TI  - The anti-hepatic fibrosis activity of ergosterol depended on upregulation of
      PPARgamma in HSC-T6 cells.
AB  - Advanced glycation endproducts (AGEs) were shown to play an important role in
      metabolic syndrome and were suggested to contribute to the development of hepatic
      fibrosis. Evidence indicates that AGEs resulted in hepatic fibrosis coupled to
      the activation of the receptor for AGEs (RAGE) in hepatic stellate cells (HSCs).
      NADPH oxidase is downstream of the RAGE signaling pathway, resulting in an
      increase in reactive oxygen species (ROS), alpha-smooth muscle actin (alpha-SMA),
      RAGE, and matrix metalloproteinase-9 (MMP-9). This study was designed to evaluate
      the effects of ergosterol on RAGE signaling in HSC-T6 cells. Ergosterol
      suppressed the activation of HSC-T6 cells induced by AGEs, and attenuated
      overexpressions of alpha-SMA, MMP-9, and epithelial-mesenchymal transition (EMT)
      markers, including N-cadherin and vimentin. We also found that these inhibitory
      effects of ergosterol on the activation of HSCs were dependent on peroxisome
      proliferator-activated receptor-gamma (PPARgamma) confirmed by PPARgamma reporter
      assay and PPARgamma knockdown. In addition, ergosterol also showed an inhibitory
      effect on the generation of AGEs, fructosamine, and alpha-dicarbonyl compounds in
      this study. Our results show that ergosterol can be used as a protective agent
      against hepatic fibrosis caused by induction of AGEs. 

PMID- 27040155
TI  - A medium range order structural connection to the configurational heat capacity
      of borate-silicate mixed glasses.
AB  - It has been reported that the configurational heat capacity (C(p,conf)) first
      increases and then becomes saturated with increasing B2O3/SiO2 ratio in borate
      silicate mixed glasses. Through Raman spectroscopy measurements, we have, in this
      work, found an implication for the intermediate range order (IRO) structural
      connection to the composition dependence of the C(p,conf) of borate-silicate
      mixed glasses. In the silica-rich compositions, the C(p,conf) rapidly increases
      with increasing B2O3 content. This is attributed to the increase of the content
      of the B-O-Si network units ([B2Si2O8](2-)) and 6-membered borate rings with 1 or
      2 B(4). In the boron-rich compositions, the C(p,conf) is almost constant,
      independent of the increase in the B2O3/SiO2 ratio. This is likely attributed to
      the counteraction between the decrease of the fraction of two types of metaborate
      groups and the increase of the fraction of other borate superstructural units
      (particularly 6-membered borate rings). The overall results suggest that the
      glasses containing more types of superstructural units have a larger C(p,conf).

PMID- 27040154
TI  - Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial.
AB  - OBJECTIVE: Carnosine is a naturally present dipeptide in humans and an over-the
      counter food additive. Evidence from animal studies supports the role for
      carnosine in the prevention and treatment of diabetes and cardiovascular disease,
      yet there is limited human data. This study investigated whether carnosine
      supplementation in individuals with overweight or obesity improves diabetes and
      cardiovascular risk factors. METHODS: In a double-blind randomized pilot trial in
      nondiabetic individuals with overweight and obesity (age 43 +/- 8 years; body
      mass index 31 +/- 4 kg/m(2) ), 15 individuals were randomly assigned to 2 g
      carnosine daily and 15 individuals to placebo for 12 weeks. Insulin sensitivity
      and secretion, glucose tolerance (oral glucose tolerance test), blood pressure,
      plasma lipid profile, skeletal muscle ((1) H-MRS), and urinary carnosine levels
      were measured. RESULTS: Carnosine concentrations increased in urine after
      supplementation (P < 0.05). An increase in fasting insulin and insulin resistance
      was hampered in individuals receiving carnosine compared to placebo, and this
      remained significant after adjustment for age, sex, and change in body weight (P
      = 0.02, P = 0.04, respectively). Two-hour glucose and insulin were both lower
      after carnosine supplementation compared to placebo in individuals with impaired
      glucose tolerance (P < 0.05). CONCLUSIONS: These pilot intervention data suggest
      that carnosine supplementation may be an effective strategy for prevention of
      type 2 diabetes.

PMID- 27040156
TI  - Meal replacements as a strategy for weight loss in obese hemodialysis patients.
AB  - Introduction There is currently limited evidence on the use or safety of meal
      replacements as part of a low- or very-low-calorie diet in patients with renal
      insufficiency; however, these are occasionally used under dietetic supervision in
      clinical practice to achieve the desired weight loss for kidney transplant. This
      case series reports on the safety and efficacy of a weight loss practice
      utilizing meal replacements among hemodialysis patients, who needed to lose
      weight for kidney transplant. Methods Five hemodialysis patients were prescribed
      a modified low-calorie diet (950 kcal and 100 g protein per day) comprising three
      meal replacements (Optifast(r) ), one main meal, and two low-potassium fruits per
      day. Dietary requirements and restrictions were met for all participants.
      Dialysis prescriptions, weight (predialysis and postdialysis), interdialytic
      weight gain, biochemistry, and medications were monitored during the study period
      for up to 12 months. Findings Participants were aged between 46 and 61 years, and
      the median time on the low-calorie diet was 364 days. Phosphate binders were
      temporarily ceased for one participant for reasons unrelated to this program and
      no other safety concerns were recorded. The low-calorie diet resulted in energy
      deficits ranging from 1170 kcal to 2160 kcal, and all participants lost weight
      (median 7% [range 5.2%-11.4%]). The most dramatic weight change appeared to occur
      by week 12, and declining adherence led to erratic weight change thereafter.
      Discussion This modified low-calorie diet was safe and effective to use in this
      population. Meal replacements are a useful weight loss strategy in hemodialysis
      patients, therefore, offering an alternative to usual weight loss protocols.

PMID- 27040157
TI  - The Evidence for Prescription Information for Possible Use of a Repeated Dose of
      Oral Triptans: A Comment.
AB  - A repeated dose of an oral triptan has been shown in randomized controlled trials
      (RCTs) to be ineffective as a treatment for no or partial response 2 hours after
      initial dosing but effective as treatment for headache recurrence. In the
      official prescription information in the United States, the United Kingdom, and
      Denmark repeated dosing of all seven oral triptans are recommended for headache
      recurrence but some triptans are also recommended for no or partial response, a
      use of a triptan deemed to be not beneficial in European and Canadian migraine
      guidelines. In summary, not all recommendations are based on evidence from RCTs.
      In addition, some recommendations are ambiguous and patients need clearer
      instructions. An example of such a clear British instruction in a patient leaflet
      instruction is presented at the end of the paper.

PMID- 27040158
TI  - Helicobacter cinaedi bacteremia resulting from antimicrobial resistance acquired
      during treatment for X-linked agammaglobulinemia.
AB  - This is the first report of penicillin/cephalosporin-resistant Helicobacter
      cinaedi arising from prolonged treatment. H. cinaedi, common among
      immunocompromised patients, caused recurrent bacteremia and cellulitis in a 19
      year-old Japanese man with X-linked agammaglobulinemia. The minimal inhibitory
      concentration of these drugs was raised, which subsequently resulted in clinical
      failure. Prolonged suboptimal treatment may cause bacterial resistance to beta
      lactam antibiotics in H. cinaedi. It is possible that this resistance may have
      contributed to the treatment failure. 

PMID- 27040159
TI  - Quality of warfarin control in atrial fibrillation patients in South East
      Queensland, Australia.
AB  - BACKGROUND: Warfarin is widely prescribed to decrease the risk of stroke in
      atrial fibrillation (AF) patients. Due to patient variability in response,
      regular monitoring is required, and time in therapeutic range (TTR) used to
      indicate quality of warfarin control with a TTR>60% is recommended. Recently, an
      Australian Government review of anticoagulants identified the need to establish
      current warfarin control and determine the potential place of the newer oral
      anticoagulants. AIM: To determine warfarin control by a pathology practice in
      Queensland, Australia and identify factors influencing TTR. METHODS:
      Retrospective data were collected from Sullivan Nicolaides Pathology, a major
      pathology practice offering a warfarin care programme in Australia. Patients
      enrolled in their programme as of September 2014 were included in the study. TTR
      was calculated using INR test results, and test dates using the Rosendaal method
      with mean patient TTR were used for analysis and comparison. Exclusions were
      target therapeutic range outside 2.0-3.0, less than two INR tests and programme
      treatment time of less than 30 days. RESULTS: The eligible 3692 AF patients had
      73.6% of INR tests within the therapeutic range. The mean TTR was 81%, with 97%
      of patients above a TTR of 60%. TTR was not significantly influenced by age,
      gender or socioeconomic factors. CONCLUSIONS: The observed mean TTR of over 80%
      is superior to the minimum recommended threshold of 60%. The TTR achieved by the
      Queensland pathology practice demonstrates that dedicated warfarin programmes can
      produce high-quality warfarin care, ensuring the full benefit of warfarin for
      Australian patients.

PMID- 27040160
TI  - Letter in response to Maderna E et al, Measles Inclusion-Body Encephalitis:
      Neuronal Phosphorylated Tau Protein Is Present in the Biopsy but Not in the
      Autoptic Specimens of the Same Patient, Brain Pathology, doi: 10.1111/bpa.12332.

PMID- 27040161
TI  - The SKG Mutation in ZAP-70 also Confers Arthritis Susceptibility in C57 Black
      Mouse Strains.
AB  - Various rodent models of arthritis are essential to dissect the full complexity
      of human rheumatoid arthritis (RA), a common autoimmune disease affecting joints.
      The SKG model of arthritis originates from a spontaneous mutation in ZAP-70 found
      in a BALB/c colony. This mutation affects T cell selection due to reduced TCR
      signalling, which allows leakage of self-reactive T cells from the thymus. To
      further expand the practical applicability of this unique model in arthritis
      research, we investigated the arthritogenicity of the SKG mutation in two common
      black mouse strains C57BL/6.Q and C57BL/10.Q and compared to BALB/c.Q. Mice
      retained the reduced TCR signalling characteristic of SKG.BALB/c mice, which
      leads to similar alteration in thymic selection. Importantly, mice also retained
      susceptibility to chronic arthritis after a single injection of mannan from
      Saccharomyces cerevisiae, with comparable prevalence and severity regardless of
      the genetic background. Further characterization of CD4(+) T cells revealed a
      similar bias towards IL-17 production and activated T cell phenotype in all SKG
      strains compared to respective wild type controls. Finally, transfer of SKG
      thymocytes conferred susceptibility to recipients, which confirm the intrinsic
      defect and pathogenicity of T cells. Overall, these results underline the strong
      impact that the W163C ZAP-70 mutation has on T cell-driven arthritis, and they
      support the use of the SKG model in black mice, which is useful for further
      investigations of this distinctive arthritis model to better understand
      autoimmunity. 

PMID- 27040162
TI  - Critical controllability in proteome-wide protein interaction network integrating
      transcriptome.
AB  - Recently, the number of essential gene entries has considerably increased.
      However, little is known about the relationships between essential genes and
      their functional roles in critical network control at both the structural
      (protein interaction network) and dynamic (transcriptional) levels, in part
      because the large size of the network prevents extensive computational analysis.
      Here, we present an algorithm that identifies the critical control set of nodes
      by reducing the computational time by 180 times and by expanding the computable
      network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm
      allows a critical controllability analysis of large integrated systems composed
      of a transcriptome- and proteome-wide protein interaction network for the first
      time. The data-driven analysis captures a direct triad association of the
      structural controllability of genes, lethality and dynamic synchronization of co
      expression. We believe that the identified optimized critical network control
      subsets may be of interest as drug targets; thus, they may be useful for drug
      design and development. 

PMID- 27040164
TI  - Editorial: in vino veritas-- transient elastography for staging liver fibrosis in
      alcoholic liver disease.

PMID- 27040163
TI  - Serial interactome capture of the human cell nucleus.
AB  - Novel RNA-guided cellular functions are paralleled by an increasing number of RNA
      binding proteins (RBPs). Here we present 'serial RNA interactome capture'
      (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA
      protein complexes that enables global RBP detection with high specificity. We
      apply serIC to the nuclei of proliferating K562 cells to obtain the first human
      nuclear RNA interactome. The domain composition of the 382 identified nuclear
      RBPs markedly differs from previous IC experiments, including few factors without
      known RNA-binding domains that are in good agreement with computationally
      predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins
      (DRBPs), and reveals a network of RBPs involved in p53 signalling and double
      strand break repair. serIC is an effective tool to couple global RBP capture with
      additional selection or labelling steps for specific detection of highly purified
      RBPs. 

PMID- 27040165
TI  - Editorial: in vino veritas--transient elastography for staging liver fibrosis in
      alcoholic liver disease--authors' reply.

PMID- 27040166
TI  - Editorial: tacrolimus vs. anti-tumour necrosis factor agents for moderately to
      severely active ulcerative colitis.

PMID- 27040167
TI  - Editorial: tacrolimus vs. anti-tumour necrosis factor agents for moderately to
      severely active ulcerative colitis--authors' reply.

PMID- 27040168
TI  - Letter: switching from one to another anti-tumour necrosis factor alpha agent,
      and the risks of an overlap of exposure.

PMID- 27040169
TI  - Letter: switching from one to another anti-tumour necrosis factor alpha agent,
      and the risks of an overlap of exposure--authors' reply.

PMID- 27040170
TI  - Letter: should HCV cirrhotics with high bilirubin or Gilbert's syndrome be
      excluded from paritaprevir, ombitasvir, or dasabuvir?

PMID- 27040171
TI  - Letter: should HCV cirrhotics with high bilirubin or Gilbert's syndrome be
      excluded from paritaprevir, ombitasvir, or dasabuvir? Authors' reply.

PMID- 27040172
TI  - Letter: increased platelet activation in chronic liver disease--hit two targets
      with a single shot.

PMID- 27040173
TI  - The atmospheric electrical index for ENSO modoki: Is ENSO modoki one of the
      factors responsible for the warming trend slowdown?
AB  - Like the southern oscillation index (SOI) based on the pressure difference
      between Tahiti (17.5 degrees S, 150 degrees W) and Darwin (12.5 degrees S, 130
      degrees E), we propose the new atmospheric electrical index (AEI) taking the
      difference in the model calculated atmospheric electrical columnar resistance
      (Rc) which involves planetary boundary layer height (PBLH) and aerosol
      concentration derived from the satellite measurements. This is the first non
      oceanic index capable of differentiating between the conventional and modoki La
      Nina and El Nino both and may be useful in the future air-sea coupling studies
      and as a complementary to the oceanic indices. As the PBLH variation over Darwin
      is within 10% of its long term mean, a strong rise in the Rc over Darwin during
      the modoki period supports modoki's connection with aerosol loading. Our
      correlation results show that the intensity of El Nino (La Nina) event is almost
      independent (not independent) of its duration and the possibility of ENSO modoki
      being one of the factors responsible for the warming trend slowdown (WTS). 

PMID- 27040174
TI  - Subterahertz dielectric relaxation in lead-free Ba(Zr,Ti)O3 relaxor
      ferroelectrics.
AB  - Relaxors are complex materials with unusual properties that have been puzzling
      the scientific community since their discovery. The main characteristic of
      relaxors, that is, their dielectric relaxation, remains unclear and is still
      under debate. The difficulty to conduct measurements at frequencies ranging from
      ?1 GHz to ?1 THz and the challenge of developing models to capture their complex
      dynamical responses are among the reasons for such a situation. Here, we report
      first-principles-based molecular dynamic simulations of lead-free
      Ba(Zr0.5Ti0.5)O3, which allows us to obtain its subterahertz dynamics. This
      approach reproduces the striking characteristics of relaxors including the
      dielectric relaxation, the constant-loss behaviour, the diffuse maximum in the
      temperature dependence of susceptibility, the substantial widening of dielectric
      spectrum on cooling and the resulting Vogel-Fulcher law. The simulations further
      relate such features to the decomposed dielectric responses, each associated with
      its own polarization mechanism, therefore, enhancing the current understanding of
      relaxor behaviour. 

PMID- 27040175
TI  - Wet etch methods for InAs nanowire patterning and self-aligned electrical
      contacts.
AB  - Advanced synthesis of semiconductor nanowires (NWs) enables their application in
      diverse fields, notably in chemical and electrical sensing, photovoltaics, or
      quantum electronic devices. In particular, indium arsenide (InAs) NWs are an
      ideal platform for quantum devices, e.g. they may host topological Majorana
      states. While the synthesis has been continously perfected, only a few techniques
      have been developed to tailor individual NWs after growth. Here we present three
      wet chemical etch methods for the post-growth morphological engineering of InAs
      NWs on the sub-100 nm scale. The first two methods allow the formation of self
      aligned electrical contacts to etched NWs, while the third method results in
      conical shaped NW profiles ideal for creating smooth electrical potential
      gradients and shallow barriers. Low temperature experiments show that NWs with
      etched segments have stable transport characteristics and can serve as building
      blocks of quantum electronic devices. As an example we report the formation of a
      single electrically stable quantum dot between two etched NW segments. 

PMID- 27040176
TI  - Synthesis of mesoporous-silica-coated Gd2O3:Eu@silica particles as cell imaging
      and drug delivery agents.
AB  - Mesoporous-silica-coated Gd2O3:Eu/silica nanoparticles were synthesized by a
      multistep chemical process and characterized by XRD, TEM and N2
      adsorption/desorption isotherms in terms of size, morphology and porosity. The
      core Gd2O3:Eu obtained by this method was highly luminescent upon excitation,
      giving the function of cell imaging upon incubation with the human cervical
      carcinoma (HeLa) cells. The outer porous silica shell is able to load the
      anticancer drug with a relatively high loading efficiency and release the loaded
      drugs at a sustained rate. The HeLa cells can be killed effectively on incubation
      with the core-shell porous particles loaded with the anticancer drug DOX.
      Meanwhile, the accumulation of mesoporous nanoparticles loaded with drugs in the
      target location could be monitored via fluorescence imaging. Therefore, the core
      shell hybrid nanoparticles presented in this work are potential multifunctional
      biomaterials for smart detection or diagnosis and therapy in future biomedical
      engineering.

PMID- 27040178
TI  - [The PRISMA statement extension for systematic reviews incorporating network meta
      analysis: PRISMA-NMA].

PMID- 27040177
TI  - Repression of GSK3 restores NK cell cytotoxicity in AML patients.
AB  - Natural killer cells from acute myeloid leukaemia patients (AML-NK) show a
      dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction
      are not fully understood. Here we show that the glycogen synthase kinase beta
      (GSK3beta) expression is elevated in AML-NK cells. Interestingly, GSK3
      overexpression in normal NK cells impairs their ability to kill AML cells, while
      genetic or pharmacological GSK3 inactivation enhances their cytotoxic activity.
      Mechanistic studies reveal that the increased cytotoxic activity correlates with
      an increase in AML-NK cell conjugates. GSK3 inhibition promotes the conjugate
      formation by upregulating LFA expression on NK cells and by inducing ICAM-1
      expression on AML cells. The latter is mediated by increased NF-kappaB activation
      in response to TNF-alpha production by NK cells. Finally, GSK3-inhibited NK cells
      show significant efficacy in human AML mouse models. Overall, our work provides
      mechanistic insights into the AML-NK dysfunction and a potential NK cell therapy
      strategy. 

PMID- 27040179
TI  - Construction of the first high-density genetic linkage map of Salvia miltiorrhiza
      using specific length amplified fragment (SLAF) sequencing.
AB  - Salvia miltiorrhiza is an important medicinal crop in traditional Chinese
      medicine (TCM). Knowledge of its genetic foundation is limited because sufficient
      molecular markers have not been developed, and therefore a high-density genetic
      linkage map is incomplete. Specific length amplified fragment sequencing (SLAF
      seq) is a recently developed high-throughput strategy for large-scale SNP (Single
      Nucleotide Polymorphisms) discovery and genotyping based on next generation
      sequencing (NGS). In this study, genomic DNA extracted from two parents and their
      96 F1 individuals was subjected to high-throughput sequencing and SLAF library
      construction. A total of 155.96 Mb of data containing 155,958,181 pair-end reads
      were obtained after preprocessing. The average coverage of each SLAF marker was
      83.43-fold for the parents compared with 10.36-fold for the F1 offspring. The
      final linkage map consists of 5,164 SLAFs in 8 linkage groups (LGs) and spans
      1,516.43 cM, with an average distance of 0.29 cM between adjacent markers. The
      results will not only provide a platform for mapping quantitative trait loci but
      also offer a critical new tool for S. miltiorrhiza biotechnology and comparative
      genomics as well as a valuable reference for TCM studies.

PMID- 27040180
TI  - Effect of soya bean and fish oil inclusion in diets on milk and plasma enzymes
      from sheep and goat related to oxidation.
AB  - This study investigated the effects of dietary inclusion of soya bean oil
      combined with fish oil (SFO) on the activities of a) superoxide dismutase (SOD),
      glutathione reductase (GR), catalase (CAT) and glutathione transferase (GST) in
      blood plasma and b) SOD, GR, CAT and lactoperoxidase (LPO) in the milk of sheep
      and goats. Furthermore, the oxidative stress indicators for measuring total
      antioxidant activity and free radical scavenging activity [ferric reducing
      ability of plasma (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
      acid) (ABTS) assays] and oxidative stress biomarkers [malondialdehyde (MDA) and
      protein carbonyl (PC)] were also determined in the blood plasma and milk of the
      animals. For this purpose, twelve dairy sheep and twelve dairy goats were
      assigned each to two homogenous subgroups. Treatments in both animal species
      involved a control diet without added oil and a diet supplemented with 5% soya
      bean oil and 1% fish oil. The results showed that the inclusion of SFO in the
      diets of sheep and goats increased significantly the activities of CAT and GR in
      their blood plasma. The same effect was observed for the activities of GST and
      FRAP in the blood plasma of goats. Moreover, the fact that the goats had
      significantly higher average daily PUFA intake (3.62 g/kg BW0.75 ) compared to
      sheep (2.51 g/kg BW0.75 ) resulted in an enhancement in the MDA content in their
      plasma. A significant increase in CAT activity in the milk in both animal species
      fed with SFO diets was also found. Finally, due to the higher apparent transfer
      rate of n-3 FA from the diet to the milk in sheep, the PC concentrations were
      found to be enhanced in their plasma and milk. In conclusion, the impact of
      dietary SFO supplementation on the oxidative status of body and/or on the milk of
      small ruminants depends not only on the daily PUFA intake, but also on the amount
      of n-3 FA that reach their milk.

PMID- 27040181
TI  - Associations Between NIH Funding and Advanced Bibliometric Indices Among
      Radiological Investigators.
AB  - RATIONALE AND OBJECTIVES: Whereas data support the h index (reflecting both
      publications and citations) as an indicator of academic productivity, other
      advanced bibliometric indices aiming to address shortcomings of the h index
      remain poorly studied. Our objective was to compare the associations between
      bibliometric indices and total National Institutes of Health (NIH) grant funding
      among investigators within U.S. academic radiology departments. MATERIALS AND
      METHODS: NIH grant funding amounts for 400 NIH-funded investigators within
      radiology departments were obtained from Blue Ridge Institute for Medical
      Research. Investigators' publications and associated citations were identified
      using Scopus. Indices computed for each investigator included: publication count,
      citation count, h index, i-10 index, hc index (h index adjusted for recency of
      publications), m quotient (h index adjusted for career duration), and e index and
      g index (both account for highly cited articles). Spearman correlations were
      performed between indices and funding. Multivariable linear regression was
      performed to identify significant independent predictors of funding. RESULTS: For
      MD investigators: the indices exhibited no-to-weak correlations with funding (r =
      0.173-0.387); m quotient exhibited the largest correlation and was the only
      significant (albeit weak) independent predictor of funding (P = 0.011). For PhD
      investigators: correlation with funding was weak for m quotient (r = 0.323),
      although moderate for other indices (r = 0.518-0.568); publication count
      exhibited highest correlation; publication count (P < 0.001) and hc index (P =
      0.024) were significant independent predictors of funding. CONCLUSIONS:
      Bibliometric indices were more strongly associated with grant funding for PhD
      than for MD radiology investigators, with publication count exhibiting the
      strongest association in the latter group. Time-weighted adjustments, as
      reflected by the m quotient and hc index, may improve efforts to predict funding
      using bibliometrics.

PMID- 27040182
TI  - Modeling single cell antibody excretion on a biosensor.
AB  - We simulated, using Comsol Multiphysics, the excretion of antibodies by single
      hybridoma cells and their subsequent binding on a surface plasmon resonance
      imaging (SPRi) sensor. The purpose was to confirm that SPRi is suitable to
      accurately quantify antibody (anti-EpCAM) excretion. The model showed that
      antibody loss by diffusion away from the sensor was less than 1%. Unexpectedly,
      more than 99% of the excreted antibodies were captured on the sensor. These data
      prove the remarkable phenomenon that the SPRi output of cellular antibody
      excretion and its subsequent binding, performed under the conditions described
      here, is directly usable for quantification of single cell antibody production
      rates.

PMID- 27040183
TI  - Field-effect transistor biosensors with two-dimensional black phosphorus
      nanosheets.
AB  - A black phosphorous (BP)-based field-effect transistor (FET) biosensor was
      fabricated by using few-layer BP nanosheets labeled with gold nanoparticle
      antibody conjugates. BP nanosheets were mechanically exfoliated and used as the
      sensing/conducting channel in the FET, with an Al2O3 thin film as the dielectric
      layer for surface passivation. Antibody probes were conjugated with gold
      nanoparticles that were sputtered on the BP through surface functionalization.
      The sensor response was measured by the change in the BP's electrical resistance
      after antigens were introduced. The adsorbed antigens through specific antigen
      antibody binding interactions induced a gate potential, thereby changing the
      drain-source current. The as-produced BP biosensor showed both high sensitivity
      (lower limit of detection ~10ng/ml) and selectivity towards human immunoglobulin
      G. Results from this study demonstrate the outstanding performance of BP as a
      sensing channel for FET biosensor applications.

PMID- 27040184
TI  - Using doubly-labelled water to measure free-living energy expenditure: Some old
      things to remember and some new things to consider.
AB  - The doubly-labelled water (DLW) method provides the ability to measure the energy
      expenditure of free-living animals based only on the injection of two isotopes in
      water (one of oxygen and one of hydrogen) and traditionally the collection of 2
      blood samples. We review here the fundamental basis of how the method works, and
      highlight how the choice of the appropriate calculation equation can have a large
      impact on the resultant estimates, particularly in species where the difference
      between the isotope elimination constants is small. This knowledge is not new,
      but is worth reiterating given the potential for error by making the wrong
      choice. In particular, it is important to remember that for mammals weighing less
      than 5kg, and birds weighing less than 2kg, the single pool models perform best
      in validation studies, while in mammals above 15kg the two-pool models perform
      best. Above 2kg in birds and between 5 and 15kg in mammals, however, the model
      superiority is uncertain. Even where the choice based on body mass would appear
      clear, the decision may need to be tempered by species specific information
      regarding potential additional sources for hydrogen turnover, such as de novo
      lipogenesis or methanogenesis. Recent advances in the technique have included
      attempts to make the method less invasive by using innovative methods for dosing
      and sample collection. In addition, the advent of laser spectroscopy, as a
      replacement technology for mass spectrometry, may open up many new opportunities
      in the field. These potentially include direct sampling of breath in the field
      and tracking background isotope drift using 17oxygen levels.

PMID- 27040185
TI  - Distribution and dynamics of branchial ionocytes in houndshark reared in full
      strength and diluted seawater environments.
AB  - In teleost fishes, it is well-established that the gill serves as an important
      ionoregulatory organ in addition to its primary function of respiratory gas
      exchange. In elasmobranchs, however, the ionoregulatory function of the gills is
      still incompletely understood. Although two types of ionocytes, Na(+)/K(+)-ATPase
      (NKA)-rich (type-A) cell and vacuolar-type H(+)-ATPase (V-ATPase)-rich (type-B)
      cell, have been found in elasmobranch fishes, these cells were considered to
      function primarily in acid-base regulation. In the present study, we examined ion
      transporting proteins expressed in ionocytes of Japanese-banded houndshark,
      Triakis scyllium, reared in full-strength seawater (SW) and transferred to
      diluted (30%) SW. In addition to the upregulation of NKA and Na(+)/H(+) exchanger
      type 3 (NHE3) mRNAs in the type-A ionocytes, we found that Na(+), Cl(-)
      cotransporter (NCC, Slc12a3) is expressed in a subpopulation of the type-B
      ionocytes, and that the expression level of NCC mRNA was enhanced in houndsharks
      transferred to a low-salinity environment. These results suggest that
      elasmobranch gill ionocytes contribute to NaCl uptake in addition to the already
      described function of acid-base regulation, and that NCC is most probably one of
      the key molecules for hyper-osmoregulatory function of elasmobranch gills. The
      existence of two types of ionocytes (NHE3- and NCC-expressing cells) that are
      responsible for NaCl absorption seems to be a common feature in both teleosts and
      elasmobranchs for adaptation to a low salinity environment. A possible driving
      mechanism for NCC in type-B ionocytes is discussed.

PMID- 27040186
TI  - Roles of mechanistic target of rapamycin and transforming growth factor-beta
      signaling in the molting gland (Y-organ) of the blackback land crab, Gecarcinus
      lateralis.
AB  - Molting in decapod crustaceans is controlled by molt-inhibiting hormone (MIH), an
      eyestalk neuropeptide that suppresses production of ecdysteroids by a pair of
      molting glands (Y-organs or YOs). Eyestalk ablation (ESA) activates the YOs,
      which hypertrophy and increase ecdysteroid secretion. At mid premolt, which
      occurs 7-14days post-ESA, the YO transitions to the committed state; hemolymph
      ecdysteroid titers increase further and the animal reaches ecdysis ~3weeks post
      ESA. Two conserved signaling pathways, mechanistic target of rapamycin (mTOR) and
      transforming growth factor-beta (TGF-beta), are expressed in the Gecarcinus
      lateralis YO. Rapamycin, an mTOR antagonist, inhibits YO ecdysteroidogenesis in
      vitro. In this study, rapamycin lowered hemolymph ecdysteroid titer in ESA G.
      lateralis in vivo; levels were significantly lower than in control animals at all
      intervals (1-14days post-ESA). Injection of SB431542, an activin TGF-beta
      receptor antagonist, lowered hemolymph ecdysteroid titers 7 and 14days post-ESA,
      but had no effect on ecdysteroid titers at 1 and 3days post-ESA. mRNA levels of
      mTOR signaling genes Gl-mTOR, Gl-Akt, and Gl-S6k were increased by 3days post
      ESA; the increases in Gl-mTOR and Gl-Akt mRNA levels were blocked by SB431542. Gl
      elongation factor 2 and Gl-Rheb mRNA levels were not affected by ESA, but
      SB431542 lowered mRNA levels at Days 3 and 7 post-ESA. The mRNA level of an
      activin TGF-beta peptide, Gl-myostatin-like factor (Mstn), increased 5.5-fold
      from 0 to 3days post-ESA, followed by a 50-fold decrease from 3 to 7days post
      ESA. These data suggest that (1) YO activation involves an up regulation of the
      mTOR signaling pathway; (2) mTOR is required for YO commitment; and (3) a Mstn
      like factor mediates the transition of the YO from the activated to the committed
      state.

PMID- 27040187
TI  - When Technology Fails: Community-Based Pediatric Hospice.

PMID- 27040188
TI  - The Transitional Experience of Family Caring for Their Child With a Tracheostomy.
AB  - The purpose of this qualitative study was to describe the family experience of
      caring for their child with a tracheostomy due to a compromised airway during the
      transition from hospital to home, and to identify types of support that families
      request to be successful caregivers. DESIGN AND METHODS: This study used a
      qualitative descriptive design with focus groups to answer semi-structured
      interview questions. The investigators followed basic content analysis to
      interpret descriptive data using three-person consensus. RESULTS: Eighteen family
      members participated. Four themes emerged: "This is not the life I had planned:
      coming to accept the new reality;" "Don't make the hospital your home; don't make
      your home a hospital;" "Caregivers engage with providers that demonstrate
      competence, confidence, attentiveness, and patience;" and "Participants value the
      opportunity to give back and help others." CONCLUSIONS: Growth in the family
      caregiver role leads to personal transformation demonstrated by increased
      confidence, finding joy from their child, becoming an advocate for their child,
      and a resource for others. Family members described the transition to being 'in
      charge,' the relationship with the provider, and being able to advocate for
      getting the resources they needed in the home. PRACTICE IMPLICATIONS:
      Relationships are as critical as teaching skills to families during
      hospitalization. Family members see considerable value in connecting with care
      providers. In addition, there is a desire to share their experience with other
      families that are beginning a similar journey. Participants requested a support
      approach that included competent providers, Web-based video education for skills
      training, family-to-family connection, and continued family group support after
      discharge.

PMID- 27040189
TI  - The effects of crosslinkers on physical, mechanical, and cytotoxic properties of
      gelatin sponge prepared via in-situ gas foaming method as a tissue engineering
      scaffold.
AB  - In this study porous gelatin scaffolds were prepared using in-situ gas foaming,
      and four crosslinking agents were used to determine a biocompatible and effective
      crosslinker that is suitable for such a method. Crosslinkers used in this study
      included: hexamethylene diisocyanate (HMDI), poly(ethylene glycol) diglycidyl
      ether (epoxy), glutaraldehyde (GTA), and genipin. The prepared porous structures
      were analyzed using Fourier Transform Infrared Spectroscopy (FT-IR), thermal and
      mechanical analysis as well as water absorption analysis. The microstructures of
      the prepared samples were analyzed using Scanning Electron Microscopy (SEM). The
      effects of the crosslinking agents were studied on the cytotoxicity of the porous
      structure indirectly using MTT analysis. The affinity of L929 mouse fibroblast
      cells for attachment on the scaffold surfaces was investigated by direct cell
      seeding and DAPI-staining technique. It was shown that while all of the studied
      crosslinking agents were capable of stabilizing prepared gelatin scaffolds, there
      are noticeable differences among physical and mechanical properties of samples
      based on the crosslinker type. Epoxy-crosslinked scaffolds showed a higher
      capacity for water absorption and more uniform microstructures than the rest of
      crosslinked samples, whereas genipin and GTA-crosslinked scaffolds demonstrated
      higher mechanical strength. Cytotoxicity analysis showed the superior
      biocompatibility of the naturally occurring genipin in comparison with other
      synthetic crosslinking agents, in particular relative to GTA-crosslinked samples.

PMID- 27040190
TI  - Rheological properties of glutaraldehyde-crosslinked collagen solutions analyzed
      quantitatively using mechanical models.
AB  - Understanding the rheological behavior of collagen solutions crosslinked by
      various amounts of glutaraldehyde (GTA) [GTA/collagen (w/w)=0-0.1] is fundamental
      either to design optimized products or to ensure stable flow. Under steady shear,
      all the samples exhibited pseudoplasticity with shear-thinning behavior, and the
      flow curves were well described by Ostwald-de Waele model and Carreau model. With
      increased amounts of GTA, the viscosity increased from 6.15 to 168.54 Pa.s at
      0.1s(-1), and the pseudoplasticity strengthened (the flow index decreased from
      0.549 to 0.117). Additionally, hysteresis loops were evaluated to analyze the
      thixotropy of the native and crosslinked collagen solutions, and indicated that
      stronger thixotropic behavior was associated with higher amount of GTA.
      Furthermore, the values of apparent yield stress were negative, and a flow index
      <1 for all the systems obtained via Herschel-Bulkley model confirmed that the
      native and crosslinked collagen solutions belonged to pseudoplastic fluid without
      apparent yield stress. However, the increment of dynamic denaturation temperature
      determined by dynamic temperature sweep was not obvious. The viscoelastic
      properties were examined based on creep-recovery measurements and then simulated
      using Burger model and a semi-empirical model. The increase in the proportion of
      recoverable compliance (instantaneous and retardant compliance) reflected that
      the crosslinked collagen solutions were more resistant to the deformation and
      exhibited more elastic behavior than the native collagen solution, accompanied by
      the fact that the compliance value decreased from 39.317 to 0.152 Pa(-1) and the
      recovery percentage increased from 1.128% to 87.604%. These data indicated that
      adjusting the amount of GTA could be a suitable mean for manipulating mechanical
      properties of collagen-based biomaterials.

PMID- 27040191
TI  - Preparation of porous carboxymethyl chitosan grafted poly (acrylic acid)
      superabsorbent by solvent precipitation and its application as a hemostatic wound
      dressing.
AB  - The volume phase transition of a hydrogel initiated by shrinking may result in
      complex patterns on its surface. Based on this unique property of hydrogel, we
      have developed a novel solvent precipitation method to prepare a kind of novel
      superabsorbent polymers with excellent hemostatic properties. A porous
      carboxymethyl chitosan grafted poly (acrylic acid) (CMCTS-g-PAA) superabsorbent
      polymer was prepared by precipitating CMCTS-g-PAA hydrogel with ethanol. Its
      potential application in hemostatic wound dressing was investigated. The results
      indicate that the modified superabsorbent polymer is non-cytotoxic. It showed a
      high swelling capacity and better hemostatic performance in the treatments of
      hemorrhage model of ear artery, arteria cruralis and spleen of the New Zealand
      white rabbit than the unmodified polymer and other commonly used clinic wound
      dressings. The hemostatic mechanism of the porous CMCTS-g-PAA polymer was also
      discussed. 

PMID- 27040192
TI  - Highly selective electrode for potentiometric analysis of methadone in biological
      fluids and pharmaceutical formulations.
AB  - In order to develop a fast and simple procedure for methadone analysis in
      biological fluids, a graphite paste electrode (GPE) was modified with the ion
      pair of methadone-phosphotungstic acid, and multiwalled carbon nanotubes
      (MWCNTs). Optimized composition of the electrode with respect to graphite
      powder:paraffin oil:MWCNTs:ion pair, was 58:30:8:4 (w/w%). The electrode showed a
      near-Nernstian slope of 58.9 +/- 0.3 mV/decade for methadone in a wide linear
      range of 1.0 * 10(-8)-4.6 * 10(-3)M, with a detection limit of 1.0 * 10(-8)M. The
      electrode response was independent of pH in the range of 5-11, with a fast
      response time (~4s) at 25  degrees C. The sensor showed high selectivity and was
      successfully applied to the determination of sub-micromolar concentrations of
      methadone in human blood serum and urine samples, with recoveries in the range of
      95-99.8%. The average recovery of methadone from tablets (5 mg/tablet) by using
      the proposed method was 98%. The life time of the modified electrode was more
      than 5 months, due to the characteristic of GPE which can be cut off and fresh
      electrode surface be available. A titration procedure was performed for methadone
      analysis by using phosphotungstic acid, as titrating agent, which showed an
      accurate end point and 1:1 stoichiometry for the ion-pair formed
      (methadone:phosphotungstic acid). The simple and rapid procedure as well as
      excellent detection limit and selectivity are some of the advantages of the
      proposed sensor for methadone.

PMID- 27040193
TI  - Preliminary assessment of metal-porcelain bonding strength of CoCrW alloy after
      3wt.% Cu addition.
AB  - In this work, a novel Cu-bearing CoCrW alloy fabricated by selective laser
      melting for dental application has been studied. For its successful application,
      the bonding strength of metal-porcelain is essential to be systematically
      investigated. Therefore, the aim of this study was to evaluate the metal
      porcelain bonding strength of CoCrWCu alloy by three-point bending test,
      meanwhile the Ni-free CoCrW alloy was used as control. The oxygen content was
      investigated by an elemental analyzer; X-ray photoelectron spectroscopy (XPS) was
      used to analyze the surface chemical composition of CoCrW based alloy after
      preoxidation treatment; the fracture mode was investigated by X-ray energy
      spectrum analysis (EDS) and scanning electron microscope (SEM). Result from the
      oxygen content analysis showed that the content of oxygen dramatically increased
      after the Cu addition. And the XPS suggested that Co-oxidation, Cr2O3, CrO2, WO3,
      Cu2O and CuO existed on the preoxidated surface of the CoCrWCu alloy; the three
      point bending test showed that the bonding strength of the CoCrWCu alloy was
      43.32 MPa, which was lower than that of the CoCrW group of 47.65 MPa. However,
      the average metal-porcelain bonding strength is significantly higher than the
      minimum value in the ISO 9693 standard. Results from the SEM images and EDS
      indicated that the fracture mode of CoCrWCu-porcelain was mixed between cohesive
      and adhesive. Based on the results obtained in this study, it can be indicated
      that the Cu-bearing CoCrW alloy fabricated by the selective laser melting is a
      promising candidate for use in dental application.

PMID- 27040194
TI  - A new biocompatible nanocomposite as a promising constituent of sunscreens.
AB  - Skin naturally uses antioxidants to protect itself from the damaging effects of
      sunlight. If this is not sufficient, other measures have to be taken. Like this,
      hydroxyapatite has the potential to be applied as an active constituent of
      sunscreens since calcium phosphate absorbs in the ultraviolet region (UV). The
      objective of the present work was to synthesize a hydroxyapatite-ascorbic acid
      nanocomposite (HAp/AA-NC) as a new biocompatible constituent of sunscreens and to
      test its efficiency with skin cell models. The synthesized HAp/AA-NC was
      characterized by Fourier transform infrared spectroscopy, transmission electron
      microscopy, absorption spectrophotometry and X-ray diffraction analysis. The
      protective effect of the construct was tested with respect to viability and
      intracellular reactive oxygen species (ROS) generation of primary human dermal
      fibroblasts (SKIN) and human epidermal keratinocytes (HaCaT). Both cell lines
      were irradiated with UV light, lambdamax=254 nm with a fluence of 25 mJ cm(-2) to
      mimic the effect of UV radiation of sunlight on the skin. Results showed that
      HAp/AA-NC had a stimulating effect on the cell viability of both, HaCaT and SKIN
      cells, relative to the irradiated control. Intracellular ROS significantly
      decreased in UV irradiated cells when treated with HAp/AA-NC. We conclude that
      the synthesized HAp/AA-NC have been validated in vitro as a skin protector
      against the harmful effect of UV-induced ROS.

PMID- 27040195
TI  - Influence of polyetheretherketone coatings on the Ti-13Nb-13Zr titanium alloy's
      bio-tribological properties and corrosion resistance.
AB  - Polyetheretherketone (PEEK) coatings of 70-90MUm thick were electrophoretically
      deposited from a suspension of PEEK powder in ethanol on near-beta Ti-13Nb-13Zr
      titanium alloy. In order to produce good quality coatings, the composition of the
      suspension (pH) and optimized deposition parameters (applied voltage and time)
      were experimentally selected. The as-deposited coatings exhibited the uniform
      distribution of PEEK powders on the substrate. The subsequent annealing at a
      temperature above the PEEK melting point enabled homogeneous, semi-crystalline
      coatings with spherulitic morphology to be produced. A micro-scratch test showed
      that the coatings exhibited very good adhesion to the titanium alloy substrate.
      Coating delamination was not observed even up to a maximal load of 30N. The PEEK
      coatings significantly improved the tribological properties of the Ti-13Nb-13Zr
      alloy. The coefficient of friction was reduced from 0.55 for an uncoated alloy to
      0.40 and 0.12 for a coated alloy in a dry sliding and sliding in Ringer's
      solution, respectively. The PEEK coatings exhibited excellent wear resistance in
      both contact conditions. Their wear rate was more than 200 times smaller compared
      with the wear rate of the uncoated Ti-13Nb-13Zr alloy. The obtained results
      indicate that electrophoretically deposited PEEK coatings on the near-beta
      titanium alloy exhibit very useful properties for their prospective tribological
      applications in medicine. 

PMID- 27040196
TI  - Enhanced bioavailability of cinnarizine nanosuspensions by particle size
      engineering: Optimization and physicochemical investigations.
AB  - Cinnarizine (CIN), a poorly soluble drug with erratic bioavailability due to pH
      dependent solubility has limited advantage to formulate oral solid dosage forms
      in subject having low gastric acidity. In present study precipitation
      ultrasonication was used to fabricate nanosuspensions of cinnarizine stabilized
      by Poly vinyl alcohol (PVA) to enhance the bioavailability. We investigated the
      effects of PVA concentration (X1) and solvent to antisolvent ratio (X2) on the
      quality attributes like mean particle size (Y1); % drug content (Y2); and time
      required to 90% drug release (Y3) via 3(2) factorial design. The morphology of
      nanosuspensions was found almost spherical by SEM observation. DSC and FT-IR
      studies revealed lack of significant interactions between CIN and PVA.
      Nanosuspensions of mean particle size 621.08 nm was achieved. The dissolution
      rate obtained from all formulations were markedly higher than pure CIN. Response
      surface methodology and optimized polynomial equations were used to select the
      optimal formulation i.e. 0.2% W/V of X1 and 1:42 of X2 to get the desired
      response Y1; 636.78 nm, Y2; 95.24% and Y3; 7.09 min that were in reasonable
      agreement with the observed value. The in-vivo study in rat demonstrated that
      Cmax and AUC0->12 values of nanosuspension were approximately 2.8-fold and 2.7
      fold greater than that of reference preparation respectively.

PMID- 27040197
TI  - Mechanical behavior of a Y-TZP ceramic for monolithic restorations: effect of
      grinding and low-temperature aging.
AB  - This study aimed to investigate the effects of grinding with diamond burs and low
      temperature aging on the mechanical behavior (biaxial flexural strength and
      structural reliability), surface topography, and phase transformation of a Y-TZP
      ceramic for monolithic dental restorations. Disc-shaped specimens (Zirlux FC,
      Ivoclar Vivadent) were manufactured according to ISO 6872 (2008) and divided in
      accordance with two factors: "grinding - 3 levels" and "LTD - 2 levels". Grinding
      was performed using a contra-angle handpiece under constant water-cooling with
      different grit-sizes (extra-fine and coarse diamond burs). LTD was simulated in
      an autoclave at 134 degrees C, under a pressure of 2 bar, over a period of 20h.
      Surface topography analysis showed an increase in roughness based on surface
      treatment grit-size (Coarse>Xfine>Ctrl), LTD did not influence roughness values.
      Both grinding and LTD promoted an increase in the amount of m-phase, although
      different susceptibilities to degradation were observed. According to existing
      literature the increase of m-phase content is a direct indicative of Y-TZP
      degradation. Weibull analysis showed an increase in characteristic strength after
      grinding (Coarse=Xfine>Ctrl), while for LTD, distinct effects were observed
      (Ctrl<Ctrl LTD; Xfine=Xfine LTD and Coarse=Coarse LTD). Weibull moduli were
      statistically similar between all tested groups. Within the limits of this
      current study, it was feasible to notice that both aging in autoclave for 20h
      (LTD) and grinding showed not to be detrimental to the mechanical properties of
      Zirlux FC Y-TZP ceramic. 

PMID- 27040198
TI  - Risedronate/zinc-hydroxyapatite based nanomedicine for osteoporosis.
AB  - Targeting of superior osteogenic drugs to bone is an ideal approach for treatment
      of osteoporosis. Here, we investigated the potential of using risedronate/zinc
      hydroxyapatite (ZnHA) nanoparticles based formulation in a rat model of
      experimental osteoporosis. Risedronate, a targeting moiety that has a strong
      affinity for bone, was loaded to ZnHA nanoparticles by adsorption method.
      Prepared risedronate/ZnHA drug formulation was characterized by field-emission
      scanning electron microscopy, X-ray diffraction analysis and fourier transform
      infrared spectroscopy. In vivo performance of the prepared risedronate/ZnHA
      nanoparticles was tested in an experimental model of postmenopausal osteoporosis.
      Therapy with risedronate/ZnHA drug formulation prevented increase in serum levels
      of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b
      better than risedronate/HA or risedronate. With respect to improvement in the
      mechanical strength of the femoral mid-shaft and correction of increase in urine
      calcium and creatinine levels, the therapy with risedronate/ZnHA drug formulation
      was more effective than risedronate/HA or risedronate therapy. Moreover,
      risedronate/ZnHA drug therapy preserved the cortical and trabecular bone
      microarchitecture better than risedronate/HA or risedronate therapy. Furthermore,
      risedronate/ZnHA drug formulation showed higher values of calcium/phosphorous
      ratio and zinc content. The results strongly implicate that risedronate/ZnHA drug
      formulation has a therapeutic advantage over risedronate or risedronate/HA
      therapy for the treatment of osteoporosis. 

PMID- 27040199
TI  - Dual-modality self-heating and antibacterial polymer-coated nanoparticles for
      magnetic hyperthermia.
AB  - Multifunctional nanoparticles for magnetic hyperthermia which simultaneously
      display antibacterial properties promise to decrease bacterial infections co
      localized with cancers. Current methods synthesize such particles by multi-step
      procedures, and systematic comparisons of antibacterial properties between
      coatings, as well as measurements of specific absorption rate (SAR) during
      magnetic hyperthermia are lacking. Here we report the novel simple method for
      synthesis of magnetic nanoparticles with shells of oleic acid (OA),
      polyethyleneimine (PEI) and polyethyleneimine-methyl cellulose (PEI-mC). We
      compare their antibacterial properties against single gram-positive
      (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria as well as
      biofilms. Magnetite nanoparticles (MNPs) with PEI-methyl cellulose were found to
      be most effective against both S. aureus and E. coli with concentration for 10%
      growth inhibition (EC10) of <150 mg/l. All the particles have high SAR and are
      effective for heat-generation in alternating magnetic fields.

PMID- 27040200
TI  - Controllable preparation of a nano-hydroxyapatite coating on carbon fibers by
      electrochemical deposition and chemical treatment.
AB  - A nano-hydroxyapatite (HA) coating with appropriate thickness and morphology
      similar to that of human bone tissue was directly prepared onto the surfaces of
      carbon fibers (CFs). A mixed solution of nitric acid, hydrochloric acid, sulfuric
      acid, and hydrogen peroxide (NHSH) was used in the preparation process. The
      coating was fabricated by combining NHSH treatment and electrochemical deposition
      (ECD). NHSH treatment is easy to operate, produces rapid reaction, and highly
      effective. This method was first used to induce the nucleation and growth of HA
      crystals on the CF surfaces. Numerous O-containing functional groups, such as
      hydroxyl (-OH) and carboxyl (-COOH) groups, were grafted onto the CF surfaces by
      NHSH treatment (NHSH-CFs); as such, the amounts of these groups on the
      functionalized CFs increased by nearly 8- and 12-fold, respectively, compared
      with those on untreated CFs. After treatment, the NHSH-CFs not only acquired
      larger specific surface areas but retained surfaces free from serious corrosion
      or breakage. Hence, NHSH-CFs are ideal depositional substrates of HA coating
      during ECD. ECD was successfully used to prepare a nano-rod-like HA coating on
      the NHSH-CF surfaces. The elemental composition, structure, and morphology of the
      HA coating were effectively controlled by adjusting various technological
      parameters, such as the current density, deposition time, and temperature. The
      average central diameter of HA crystals and the coating density increased with
      increasing deposition time. The average central diameter of most HA crystals on
      the NHSH-CFs varied from approximately 60 nm to 210 nm as the deposition time
      increased from 60 min to 180 min. Further studies on a possible deposition
      mechanism revealed that numerous O-containing functional groups on the NHSH-CF
      surfaces could associate with electrolyte ions (Ca(2+)) to form special chemical
      bonds. These bonds can induce HA coating deposition and improve the interfacial
      bonding strength between the HA coating and NHCH-CFs. The results of this study
      and the proposed preparation of uniform and dense nano-HA coating provide
      theoretical and practical guidance for future investigations of active HA
      coatings on fiber materials for medical products and implants. This work also
      lays the foundation for the wider use of HA-coated CFs/HA composite implants in
      clinical application.

PMID- 27040201
TI  - Synthesis of polyester urethane urea and fabrication of elastomeric nanofibrous
      scaffolds for myocardial regeneration.
AB  - Fabrication of bioactive scaffolds is one of the most promising strategies to
      reconstruct the infarcted myocardium. In this study, we synthesized polyester
      urethane urea (PEUU), further blended it with gelatin and fabricated PEUU/G
      nanofibrous scaffolds. Attenuated total reflectance Fourier transform infrared
      spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and X-ray
      diffraction were used for the characterization of the synthesized PEUU and
      properties of nanofibrous scaffolds were evaluated using scanning electron
      microscopy (SEM), ATR-FTIR, contact angle measurement, biodegradation test,
      tensile strength analysis and dynamic mechanical analysis (DMA). In vitro
      biocompatibility studies were performed using cardiomyocytes. DMA analysis showed
      that the scaffolds could be reshaped with cyclic deformations and might remain
      stable in the frequencies of the physiological activity of the heart. On the
      whole, our study suggests that aligned PEUU/G 70:30 nanofibrous scaffolds meet
      the required specifications for cardiac tissue engineering and could be used as a
      promising construct for myocardial regeneration. 

PMID- 27040202
TI  - Coaxially electrospun fiber-based microbicides facilitate broadly tunable release
      of maraviroc.
AB  - Electrospun fibers show potential as a topical delivery system for vaginal
      microbicides. Previous reports have demonstrated delivery of anti-HIV and anti
      STI (sexually transmitted infection) agents from fibers formulated using
      hydrophilic, hydrophobic, or pH-responsive polymers that result in rapid,
      prolonged, or stimuli-responsive release, respectively. However, coaxial
      electrospun fibers have yet to be evaluated as a highly tunable microbicide
      delivery vehicle. In this research, we explored the opportunities and limitations
      of a model coaxial electrospun fiber system to provide broad and tunable release
      rates for the HIV entry inhibitor maraviroc. Specifically, we prepared ethyl
      cellulose (EC)-shell and polyvinylpyrrolidone (PVP)-core fibers that were capable
      of releasing actives over a range of hours to several days. We further
      demonstrated simple and effective methods for combining core-shell fibers with
      rapid-release formulations to provide combined instantaneous and sustained
      maraviroc release. In addition, we investigated the effect of varying release
      media on maraviroc release from core-shell fibers, and found that release was
      strongly influenced by media surface tension and drug ionization. Finally, in
      vitro cell culture studies show that our fiber formulations were not cytotoxic
      and that electrospun maraviroc maintained similar antiviral activity compared to
      neat maraviroc. 

PMID- 27040203
TI  - In Vivo evaluation of adipogenic induction in fibrous and honeycomb-structured
      atelocollagen scaffolds.
AB  - Nowadays, soft tissue restoration techniques are mainly focused on volume
      regeneration instead of function recovering. So far, autologous fat transplant
      has been the most popular method although its multiple reported problems like
      volume and function loss. Adipose tissue engineering therefore emerges as a
      solution for development of biological substitutes for soft tissue which promotes
      not only volume regeneration but also function restoration with minimal
      consequences. Here we tested fibrous-structured atelocollagen (FSA) scaffolds and
      honeycomb atelocollagen (HCA) scaffolds for their ability to induce adipogenesis
      in vivo. Implants were subjected to histological and immunohistochemical
      assessment after 1, 2, and 4 weeks of implantation. Our studies showed that FSA
      scaffolds induced in vivo a markedly adipogenic response, whereas an acute
      inflammatory process was observed at HCA scaffolds without tissue regeneration
      detected within them. Our histological findings concerning FSA scaffolds clearly
      showed the presence of adipose-like tissue surprisingly composed by a mixture of
      brown-like and white-like adipocytes at week 2 whereas only white-like adipocytes
      at week 4. Subsequent positive Pax7 immunostaining at weeks 1 and 2 suggested the
      existence of a common myogenic progenitor shared by brown-like and white-like
      adipocytes observed. Then, in this work we present FSA scaffolds as a promising
      structure for brown and white adipose tissue engineering.

PMID- 27040204
TI  - Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for
      cardiac tissue engineering.
AB  - Injectable hydrogels that resemble electromechanical properties of the myocardium
      are crucial for cardiac tissue engineering prospects. We have developed a facile
      approach that uses chitosan (CS) to generate a thermosensitive conductive
      hydrogel with a highly porous network of interconnected pores. Gold nanoparticles
      (GNPs) were evenly dispersed throughout the CS matrix in order to provide
      electrical cues. The gelation response and electrical conductivity of the
      hydrogel were controlled by different concentrations of GNPs. The CS-GNP
      hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to
      14 days in the absence of electrical stimulations. CS-GNP scaffolds supported
      viability, metabolism, migration and proliferation of MSCs along with the
      development of uniform cellular constructs. Immunohistochemistry for early and
      mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs
      within the CS-GNP compared to the CS matrix alone. The results of this study
      demonstrate that incorporation of nanoscale electro-conductive GNPs into CS
      hydrogels enhances the properties of myocardial constructs. These constructs
      could find utilization for regeneration of other electroactive tissues.

PMID- 27040205
TI  - In-situ formation of silver nanoparticles on poly (lactic acid) film by gamma
      radiation induced grafting of N-vinyl pyrrolidone.
AB  - A fast, easy and novel method for preparing biodegradable polymer films with
      silver nanoparticles was investigated to endow the material with excellent
      biocompatibility and antibacterial property. Silver nanoparticles (Ag NPs) were
      immobilized on the surface of polylactic acid (PLA) film by gamma radiation
      induced grafting of N-vinyl pyrrolidone (NVP). In this method, poly (N-vinyl
      pyrrolidone) (PVP) was produced and grafted onto the surface of PLA film by gamma
      radiation polymerization of NVP. PVP acted as both a bridge to connect the Ag NPs
      with the PLA film, and a stabilizer to protect the Ag NPs from agglomeration. The
      effect of various reaction parameters, including NVP/Ag mole ratio and radiation
      dose, on the fabrication of PLA-g-NVP/Ag film was demonstrated. Moreover, the
      interaction between PVP and Ag NPs was studied by X-ray photoelectron
      spectroscopy and Fourier-transform infrared spectroscopy, that revealed the Ag
      NPs coordinated through the oxygen atom on the carbonyl group of PVP at 15 kGy
      radiation dose, but through the nitrogen atom and the oxygen atom of the amide
      group of PVP at 1 kGy dose.

PMID- 27040206
TI  - Non-enzymatic glucose biosensor based on hyperbranched pine-like gold
      nanostructure.
AB  - Hyperbranched pine-like gold nanostructure was electrodeposited on the
      polycrystalline gold surface at 0 mV (vs. AgCl) with the assistance of histidine
      as a soft template. The nanostructure was then applied as a highly sensitive
      nonenzymatic sensor for glucose. The catalytic activity and sensitivity of the
      gold nanostructure toward the electrooxidation of glucose was excellent without
      surface fouling and deterioration effects. The current related to the oxidation
      of glucose rapidly and linearly depended on its concentration with a sensitivity
      of 776.8 MUA cm(-2)mmol(-1)dm(3), a detection limit of 3.39 MUmol dm(-3) with a
      relative standard deviation of 2.32%.

PMID- 27040207
TI  - Evaluation of physicochemical properties of SiO2-coated stainless steel after
      sterilization.
AB  - The study of most of the literature devoted to the use of coronary stents
      indicates that their efficiency is determined by the physicochemical properties
      of the implant surface. Therefore, the authors of this study suggested conditions
      for the formation of SiO2 layers obtained with the use of sol-gel methodology
      showing physicochemical properties adequate to the specific conditions of the
      cardio-vascular system. Previous experience of authors helped them much to
      optimize the coating of 316LVM steel surface with SiO2. The values of parameters
      that determine the usefulness of the coating in medical applications have been
      determined. In order to identify the phenomena taking place at the boundary of
      phases and to evaluate the usefulness of the proposed surface modification,
      taking into consideration the medical sterilization (steam or ethylene oxide
      (EO)), the potentiodynamic, impedance, adhesion, surface morphology and
      biological assessment characterizations were performed. Regardless of the usage
      of the sterilizing agent (steam, EO) the study showed the reduction of critical
      force causing layer's delamination. The research results of corrosion resistance
      study also confirmed a slight decrease of SiO2 barrier properties of the samples
      after sterilization in contact with the artificial plasma. SiO2 layers after the
      sterilization process did not show significant features of cytotoxicity and had
      no negative influence on blood cell counts, which confirmed the results of
      quantitative and qualitative studies. 

PMID- 27040208
TI  - Comparison of the fracture resistance of dental implants with different abutment
      taper angles.
AB  - To investigate the effects of abutment taper angles on the fracture strength of
      dental implants with TIS (taper integrated screwed-in) connection. Thirty
      prototype cylindrical titanium alloy 5.0mm-diameter dental implants with
      different TIS-connection designs were divided into six groups and tested for
      their fracture strength, using a universal testing machine. These groups
      consisted of combinations of 3.5 and 4.0 mm abutment diameter, each with taper
      angles of 6 degrees , 8 degrees  or 10 degrees . 3-Dimensional finite element
      analysis (FEA) was also used to analyze stress states at implant-abutment
      connection areas. In general, the mechanical tests found an increasing trend of
      implant fracture forces as the taper angle enlarged. When the abutment diameter
      was 3.5 mm, the mean fracture forces for 8 degrees  and 10 degrees  taper groups
      were 1638.9 N +/- 20.3 and 1577.1 N +/- 103.2, respectively, both larger than
      that for the 6 degrees  taper group of 1475.0 N +/- 24.4, with the largest
      increasing rate of 11.1%. Furthermore, the difference between 8 degrees  and 6
      degrees  taper groups was significant, based on Tamhane's multiple comparison
      test (P<0.05). In 4.0 mm-diameter abutment groups, as the taper angle was
      enlarged from 6 degrees  to 8 degrees  and 10 degrees , the mean fracture value
      was increased from 1066.7 N +/- 56.1 to 1241.4 N +/- 6.4 and 1419.3 N +/- 20.0,
      with the largest increasing rate of 33.1%, and the differences among the three
      groups were significant (P<0.05). The FEA results showed that stress values
      varied in implants with different abutment taper angles and supported the
      findings of the static tests. In conclusion, increases of the abutment taper
      angle could significantly increase implant fracture resistance in most cases
      established in the study, which is due to the increased implant wall thickness in
      the connection part resulting from the taper angle enlargement. The increasing
      effects were notable when a thin implant wall was present to accommodate wide
      abutments.

PMID- 27040209
TI  - Preparation of bone-implants by coating hydroxyapatite nanoparticles on self
      formed titanium dioxide thin-layers on titanium metal surfaces.
AB  - Preparation of hydroxyapatite coated custom-made metallic bone-implants is very
      important for the replacement of injured bones of the body. Furthermore, these
      bone-implants are more stable under the corrosive environment of the body and
      biocompatible than bone-implants made up of pure metals and metal alloys. Herein,
      we describe a novel, simple and low-cost technique to prepare biocompatible
      hydroxyapatite coated titanium metal (TiM) implants through growth of self-formed
      TiO2 thin-layer (SFTL) on TiM via a heat treatment process. SFTL acts as a
      surface binder of HA nanoparticles in order to produce HA coated implants.
      Colloidal HA nanorods prepared by a novel surfactant-assisted synthesis method,
      have been coated on SFTL via atomized spray pyrolysis (ASP) technique. The
      corrosion behavior of the bare and surface-modified TiM (SMTiM) in a simulated
      body fluid (SBF) medium is also studied. The highest corrosion rate is found to
      be for the bare TiM plate, but the corrosion rate has been reduced with the heat
      treatment of TiM due to the formation of SFTL. The lowest corrosion rate is
      recorded for the implant prepared by heat treatment of TiM at 700  degrees C. The
      HA-coating further assists in the passivation of the TiM in the SBF medium. Both
      SMTiM and HA coated SMTiM are noncytotoxic against osteoblast-like (HOS) cells
      and are in high-bioactivity. The overall production process of bone-implant
      described in this paper is in high economic value.

PMID- 27040210
TI  - Highly sensitive covalently functionalized light-addressable potentiometric
      sensor for determination of biomarker.
AB  - A biomarker is related to the biological status of a living organism and shows
      great promise for the early prediction of a related disease. Herein we presented
      a novel structured light-addressable potentiometric sensor (LAPS) for the
      determination of a model biomarker, human immunoglobulin G (hIgG). In this
      system, the goat anti-human immunoglobulin G antibody was used as recognition
      element and covalently immobilized on the surface of light-addressable
      potentiometric sensor chip to capture human immunoglobulin G. Due to the light
      addressable capability of light-addressable potentiometric sensor, human
      immunoglobulin G dissolved in the supporting electrolyte solution can be detected
      by monitoring the potential shifts of the sensor. In order to produce a stable
      photocurrent, the laser diode controlled by field-programmable gate array was
      used as the light emitter to drive the light-addressable potentiometric sensor. A
      linear correlation between the potential shift response and the concentration of
      human immunoglobulin G was achieved and the corresponding regression equation was
      DeltaV (V)=0.00714ChIgG (MUg/mL)-0.0147 with a correlation coefficient of 0.9968
      over a range 0-150 MUg/mL. Moreover, the light-addressable potentiometric sensor
      system also showed acceptable stability and reproducibility. All the results
      demonstrated that the system was more applicable to detection of disease
      biomarkers with simple operation, multiple-sample format and might hold great
      promise in various environmental, food, and clinical applications.

PMID- 27040211
TI  - Surface corrosion enhancement of passive films on NiTi shape memory alloy in
      different solutions.
AB  - The corrosion behaviors of NiTi shape memory alloy in NaCl solution, H2SO4
      solution and borate buffer solution were investigated. It was found that TiO2 in
      passive film improved the corrosion resistance of NiTi shape memory. However, low
      corrosion resistance of passive film was observed in low pH value acidic solution
      due to TiO2 dissolution. Moreover, the corrosion resistance of NiTi shape memory
      alloy decreased with the increasing of passivated potential in the three
      solutions. The donor density in passive film increased with the increasing of
      passivated potential. Different solutions affect the semiconductor
      characteristics of the passive film. The reducing in the corrosion resistance was
      attributed to the more donor concentrations in passive film and thinner thickness
      of the passive film. 

PMID- 27040212
TI  - Characterization of slow-gelling alginate hydrogels for intervertebral disc
      tissue-engineering applications.
AB  - Reversal of intervertebral disc degeneration can have a potentially monumental
      effect on spinal health. As such, the goal of this research is to create an
      injectable, cellularized alginate-based nucleus pulposus that will restore disc
      function; with the primary goal of creating an alginate gel with tailorable rates
      of gelation to improve functionality over standard CaCl2 crosslinking techniques.
      Gelation characteristics of 1% sodium alginate were analyzed over various molar
      concentrations of a 1:2 ratio of CaCO3:glucono-delta-lactone (GDL), with 10%
      CaCl2 as the control crosslinker. Alginate construct characterization for all
      concentrations was performed via ultimate and cyclic compressive testing over a
      28day degradation period in PBS. Dehydration, swell testing, and albumin release
      kinetics were determined, and cytotoxicity and cell homogeneity tests showed
      promise for cellularization strategies. Overall, the 30 and 60mM GDL alginate
      concentrations presented the most viable option for use in further studies, with
      a gelation time between 10 and 30min, low hysteresis over control, low percent
      change in thickness and weight under both PBS degradation and swelling
      conditions, and stable mechanical properties over 28days in vitro. 

PMID- 27040213
TI  - Impedance spectroscopy and mechanical response of porous nanophase hydroxyapatite
      barium titanate composite.
AB  - The present study aims to develop the porous nanophase hydroxyapatite (HA)-barium
      titanate (BT) composite with reasonable mechanical and electrical properties as
      an electrically-active prosthetic orthopedic implant alternate. The porous
      samples (densification ~40-70%) with varying amounts of BT (0, 25, 35 and 100
      vol.%) in HA were synthesized using optimal spark plasma sintering conditions,
      which revealed the thermochemical stability between both the phases. The
      reasonably good combination of functional properties such as compressive [(236.00
      +/- 44.90)MPa] and flexural [(56.18 +/- 5.82) MPa] strengths, AC conductivity
      [7.62 * 10(-9)(ohm-cm)(-1) at 10 kHz] and relative permittivity [15.20 at 10 kHz]
      have been achieved with nanostructured HA-25 vol.% BT composite as far as
      significant sample porosity (~30%) is concerned. Detailed impedance spectroscopic
      analysis was performed to reveal the electrical microstructure of developed
      porous samples. The resistance and capacitance values (at 500  degrees C) of
      grain (RG, CG) and grain boundary (RGB, CGB) for the porous HA-25 vol.% BT
      composite are (1.3 * 10(7) ohm, 3.1 * 10(-11)F) and (1.6 * 10(7) ohm, 5.9 * 10(
      10)F), respectively. Almost similar value of activation energy (~1-1.5 eV) for
      grain and grain boundary has been observed for all the samples. The mechanism of
      conduction is found to be same for porous monolithic HA as well as composite
      samples. Relaxation spectroscopic analyses suggest that both the localized as
      well as long range charge carrier translocations are responsible for conduction
      in these samples. The degree of polarization of porous samples has been assessed
      by measuring thermally stimulated depolarization current of the poled samples.
      The depolarization current is observed to depend on the heating rate. The maximum
      current density, measured for HA-25 vol.% BT sample at a heating rate of 1 
      degrees C/min is 2.7 nA/cm(2). Formation of oxygen vacancies due to the reduced
      atmosphere sintering contribute to the space charge polarization, which is
      obtained as the dominant polarization mechanism in the developed porous samples.
      Overall, such integrated functional responses do establish spark plasma sintered
      porous HA-BaTiO3 nanocomposite as potential alternative for electroactive
      prosthetic orthopedic implants.

PMID- 27040214
TI  - Dependence of corneal keratocyte adhesion, spreading, and integrin beta1
      expression on deacetylated chitosan coating.
AB  - This study reports, for the first time, the regulation of corneal keratocyte
      adhesion, spreading, morphology, and integrin gene expression on chitosan coating
      due to the effects of deacetylation. The degree of deacetylation (DD) in chitosan
      materials was confirmed by elemental analysis, gel permeation chromatography, and
      Fourier transform infrared spectroscopy. In this study, chitosan samples with the
      same molecular weight level but varying DD (74.1 +/- 0.5%, 84.4 +/- 0.7%, and
      94.2 +/- 0.5%) were obtained by heat-alkaline treatment under a nitrogen
      atmosphere. For higher DD groups, the biopolymer carried abundant amino groups
      since the deacetylation process removed larger amount of acetyl groups from the
      chitosan molecules. Results showed that the mechanical stability and
      crystallinity of the chitosan coatings significantly increased with increasing DD
      value. Fibronectin adsorption, keratocyte adhesion, and cell spreading exhibited
      a positive correlation with DD due to the chemical functionality of
      polysaccharides (bearing acetyl and amino groups) and increase of substrate
      stiffness and crystallinity. In particular, when adhered to chitosan coatings
      with a DD value of 74.1%, the keratocytes appeared to be fibroblastic, elongated,
      and spindle shape, indicating a loss of their characteristic dendritic
      morphology. Furthermore, the gene expression of integrin beta1 (i.e., a cell
      matrix adhesion molecule) was significantly up-regulated on the chitosan coatings
      with higher DD, which supports favorable attachment of corneal keratocytes. Our
      findings suggest that DD-mediated physicochemical properties of chitosan coatings
      greatly affect cell-substrate crosstalk during corneal keratocyte cultivation.

PMID- 27040215
TI  - Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun
      polylactic acid nanofibers: Release behavior and antioxidant activity of gallic
      acid.
AB  - Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and
      pharmaceutical industries due to their enhanced ability for stabilization of
      active compounds during processing, storage and usage. Here, CD-IC of gallic acid
      (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPbetaCD-IC) was prepared and then
      incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPbetaCD-IC-NF) using
      electrospinning technique to observe the effect of CD-ICs in the release behavior
      of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA
      incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility
      studies showed an enhanced solubility of GA with increasing amount of HPbetaCD.
      The detailed characterization techniques (XRD, TGA and (1)H-NMR) confirmed the
      formation of inclusion complex between GA and HPbetaCD. Computational modeling
      studies indicated that the GA made an efficient complex with HPbetaCD at 1:1
      either in vacuum or aqueous system. SEM images revealed the bead-free and uniform
      morphology of PLA/GA/HPbetaCD-IC-NF. The release studies of GA from
      PLA/GA/HPbetaCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and
      95% ethanol, and the findings revealed that PLA/GA/HPbetaCD-IC-NF has released
      much more amount of GA in water and 10% ethanol system when compared to PLA/GA
      NF. In addition, GA was released slowly from PLA/GA/HPbetaCD-IC-NF into 95%
      ethanol when compared to PLA/GA-NF. It was also observed that electrospinning
      process had no negative effect on the antioxidant activity of GA when GA was
      incorporated in PLA nanofibers. 

PMID- 27040216
TI  - Effects of RGD immobilization on light-induced cell sheet detachment from TiO2
      nanodots films.
AB  - Light-induced cell detachment is reported to be a safe and effective cell sheet
      harvest method. In the present study, the effects of arginine-glycine-aspartic
      acid (RGD) immobilization on cell growth, cell sheet construction and cell
      harvest through light illumination are investigated. RGD was first immobilized on
      TiO2 nanodots films through simple physical adsorption, and then mouse pre
      osteoblastic MC3T3-E1 cells were seeded on the films. It was found that RGD
      immobilization promoted cell adhesion and proliferation. It was also observed
      that cells cultured on RGD immobilized films showed relatively high level of pan
      cadherin. Cells harvested with ultraviolet illumination (365 nm) showed good
      viability on both RGD immobilized and unmodified TiO2 nanodot films. Single cell
      detachment assay showed that cells detached more quickly on RGD immobilized TiO2
      nanodot films. That could be ascribed to the RGD release after UV365
      illumination. The current study demonstrated that RGD immobilization could
      effectively improve both the cellular responses and light-induced cell harvest.

PMID- 27040217
TI  - Synthesis of nano-sized stereoselective imprinted polymer by copolymerization of
      (S)-2-(acrylamido) propanoic acid and ethylene glycol dimethacrylate in the
      presence of racemic propranolol and copper ion.
AB  - A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was obtained
      by reaction of (l)-alanine with acryloyl chloride. The resulting monomer was
      characterized by FT-IR and HNMR and then utilized for the preparation of chiral
      imprinted polymer (CIP). This was carried out by copolymerization of (l)-alanine
      derived chiral monomer and ethylene glycol dimethacrylate, in the presence of
      racemic propranolol and copper nitrate, via precipitation polymerization
      technique, resulting in nano-sized networked polymer particles. The polymer
      obtained was characterized by scanning electron microscopy and FT-IR. The non
      imprinted polymer was also synthesized and used as blank polymer. Density
      functional theory (DFT) was also employed to optimize the structures of two
      diasterometric ternary complexes, suspected to be created in the pre
      polymerization step, by reaction of optically active isomers of propranolol,
      copper ion and (S)-2-(acrylamido) propanoic acid. Relative energies and other
      characteristics of the described complexes, calculated by the DFT, predicted the
      higher stability of (S)-propranolol involved complex, compared to (R)-propranolol
      participated complex. Practical batch extraction test which employed CIP as solid
      phase adsorbent, indicated that the CIP recognized selectively (S)-propranolol in
      the racemic mixture of propranolol; whereas, the non-imprinted polymer (NIP)
      showed no differentiation capability between two optically active isomers of
      propranolol. 

PMID- 27040218
TI  - Comparison of wear behaviors for an artificial cervical disc under
      flexion/extension and axial rotation motions.
AB  - The wear behaviors of a ball-on-socket (UHMWPE-on-Ti6Al4V) artificial cervical
      disc were studied with 1.5 MC (million cycles) wear simulation under single
      flexion/extension and axial rotation motion and their composite motion. The wear
      rates, wear traces, and contact stress were analyzed and contrasted based on mass
      loss, optical microscopy and SEM as well as 3D profilometer, and ANSYS software,
      respectively. A much higher wear rate and more severe wear scars appeared under
      multi-directional motion. Flexion/extension motion of 7.5 degrees  lead to more
      severe wear than that under axial rotation motion of 4 degrees . The above
      results were closely related to the contact compression stress and shear stress.
      The wear surface in FE motion showed typical linear wear scratches while
      revealing obvious arc-shaped wear tracks in AR motion. However, the central zone
      of both ball and socket components revealed more severe wear tracks than that in
      the edge zone under these two different motions. The dominant wear mechanism was
      plowing/scratching and abrasive wear as well as a little oxidation wear for the
      titanium socket while it was scratching damage with adhesive wear and fatigue
      wear due to plastic deformation under cyclic load and motion profiles for the
      UHMWPE ball.

PMID- 27040219
TI  - Fabrication and characterization of Pluronic modified poly(hydroxybutyrate)
      fibers for potential wound dressing applications.
AB  - Electrospun poly(hydroxybutyrate) (PHB) fiber meshes have shown some success in
      wound dressing applications, however, their use is limited by their high
      hydrophobicity and brittle nature. In this study we investigated the effect of
      hydrophilization of electrospun PHB fibers by blending with Pluronic F-108 (PF)
      for use as a wound dressing material. Blending of PHB with different
      concentrations of PF (0.5%PF-PHB and 1.0% PF-PHB) before electrospinning led to a
      significant increase in the water wettability and swelling properties of fibers
      as compared to pristine PHB fibers. Further, it was observed that though the
      tensile moduli of PF blended PHB fibers were relatively lower as compared to PHB
      fibers, they show higher resistance to failure measured in terms of strain to
      failure and energy to failure. Moreover, PF blending significantly improved the
      in vitro blood clotting rate on PHB fibers when compared to control PHB fibers.
      Furthermore, the fabricated fiber systems were found to be cytocompatible and
      supported adhesion of fibroblasts in vitro. Finally, it was demonstrated that the
      PF blended fiber systems were suitable for the encapsulation of an antibiotic
      (doxycycline) to render them with antibacterial properties. Taken together, this
      study demonstrates that PF blending can be used to significantly improve
      properties of PHB fibers for wound dressing applications. 

PMID- 27040220
TI  - Injectable alginate/hydroxyapatite gel scaffold combined with gelatin
      microspheres for drug delivery and bone tissue engineering.
AB  - Injectable and biodegradable alginate-based composite gel scaffolds doubly
      integrated with hydroxyapatite (HAp) and gelatin microspheres (GMs) were cross
      linked via in situ release of calcium cations. As triggers of calcium cations,
      CaCO3 and glucono-D-lactone (GDL) were fixed as a mass ratio of 1:1 to control pH
      value ranging from 6.8 to 7.2 during gelation. Synchronously, tetracycline
      hydrochloride (TH) was encapsulated into GMs to enhance bioactivity of composite
      gel scaffolds. The effects of HAp and GMs on characteristics of gel scaffolds,
      including pH value, gelation time, mechanical properties, swelling ratio,
      degradation behavior and drug release, were investigated. The results showed that
      HAp and GMs successfully improved mechanical properties of gel scaffolds at
      strain from 0.1 to 0.5, which stabilized the gel network and decreased weight
      loss, as well as swelling ratio and gelation time. TH could be released from this
      composite gel scaffold into the local microenvironment in a controlled fashion by
      the organic/inorganic hybrid of hydrogel network. Our results demonstrate that
      the HAp and GMs doubly integrated alginate-based gel scaffolds, especially the
      one with 6% (w/v) HAp and 5% (w/v) GMs, have suitable physical performance and
      bioactive properties, thus provide a potential opportunity to be used for bone
      tissue engineering. The potential application of this gel scaffold in bone tissue
      engineering was confirmed by encapsulation behavior of osteoblasts. In
      combination with TH, the gel scaffold exhibited beneficial effects on osteoblast
      activity, which suggested a promising future for local treatment of pathologies
      involving bone loss.

PMID- 27040221
TI  - Preparation, characterization and properties of nano-hydroxyapatite/polypropylene
      carbonate biocomposite.
AB  - The combination of nano-hydroxyapatite (n-HA) and polypropylene carbonate (PPC)
      was used to make a composite materials by a coprecipitation method. The physical
      and chemical properties of the composite were tested. Scanning electron
      microscope (SEM) observation indicated that the biomimetic n-HA crystals were
      uniformly distributed in the polymer matrix. As the n-HA content increased in the
      composite, the fracture mechanism of the composites changes from gliding fracture
      to gliding and brittle fracture. Furthermore, the chemical interaction between
      inorganic n-HA and polypropylene carbonate was also investigated and discussed in
      detail. The hydrogen bonds might be formed between -OH/CO3(2-) of n-HA crystal
      and the ester group (-COO-) of PPC. The tensile strength of n-HA/PPC (40/60) was
      similar to that of the cancellous bone, and reached ca 58 MPa. The osteoblasts
      were cultured for up to 7 days, and then the adhesion and proliferation of
      osteoblasts were measured by Methyl thiazolyl tetrazolium (MTT) colorimetry assay
      and SEM. The cells proliferated, grew normally in fusiform shape and well
      attached. The in vitro test confirmed that the n-HA/PPC composites were
      biocompatible and showed undetectable negative effect on osteoblasts. In vivo
      implantation of the composite in New Zealand white rabbits was performed. It can
      stimulate the growth of a new bone, and at the same time the material begins to
      degrade. These results suggested that the composite may be suitable for the
      reparation or replacement of bone defects and possessed the potential for
      clinical applications.

PMID- 27040222
TI  - Finite element analysis on influence of implant surface treatments, connection
      and bone types.
AB  - The aim of this study is to assess the effect of different dental implant
      designs, bone type, loading, and surface treatment on the stress distribution
      around the implant by using the 3D finite-element method. Twelve 3D models were
      developed with Invesalius 3.0, Rhinoceros 4.0, and Solidworks 2010 software. The
      analysis was processed using the FEMAP 10.2 and NeiNastran 10.0 software. The
      applied oblique forces were 200 N and 100 N. The results were analyzed using maps
      of maximum principal stress and bone microstrain. Statistical analysis was
      performed using ANOVA and Tukey's test. The results showed that the Morse taper
      design was most efficient in terms of its distribution of stresses (p<0.05); the
      external hexagon with platform switching did not show a significant difference
      from an external hexagon with a standard platform (p>0.05). The different bone
      types did not show a significant difference in the stress/strain distribution
      (p>0.05). The surface treatment increased areas of stress concentration under
      axial loading (p<0.05) and increased areas of microstrain under axial and oblique
      loading (p<0.05) on the cortical bone. The Morse taper design behaved better
      biomechanically in relation to the bone tissue. The treated surface increased
      areas of stress and strain on the cortical bone tissue.

PMID- 27040223
TI  - Effect of LED-LCU light irradiance distribution on mechanical properties of resin
      based materials.
AB  - The objective of this study is to analyze the light power distribution along the
      tip end of the light guide of three LED-LCUs (Light Curing Units) and to evaluate
      its effect on the mechanical properties of a polymer based dental composite.
      Firstly, the light power distribution over the whole area of LED-LCU light guide
      surface was analyzed by three methods: visual projection observation, spectral
      measurement and optical spectral analysis (OSA). The light power distribution and
      the total irradiance were different for the three LEDs used, but the wavelength
      was within the camphorquinone absorption spectrum. The use of a blank sheet was
      quite on hand to make a qualitative analysis of a beam, and it is costless.
      Secondly, specimens of a hybrid composite with approximately 8mm diameter and 2mm
      thickness were produced and polymerized by 20s exposition time to each LED-LCU.
      Thirdly, the elastic modulus (E) and hardness (HV) were measured throughout the
      irradiated area by instrumented micro-indentation test (IIT), allowing to
      correlate localized power and mechanical properties. Both E and HV showed to be
      very sensitive to local power and wavelength dependent, but they followed the
      beam power profile. It was also shown that the mechanical properties could be
      directly correlated to the curing process. Very steep differences in mechanical
      properties over very short distances may impair the material performance, since
      residual stresses can easily be built over it. 

PMID- 27040224
TI  - Wet-laid soy fiber reinforced hydrogel scaffold: Fabrication, mechano
      morphological and cell studies.
AB  - Among materials used in biomedical applications, hydrogels have received
      consistent linear growth in interest over the past decade due to their large
      water volume and saliency to the natural extracellular matrix. These materials
      are often limited due to their sub-optimal mechanical properties which are
      typically improved via chemical or physical crosslinking. Chemical crosslinking
      forms strong inter-polymer bonds but typically uses reagents that are cytotoxic
      while physical crosslinking is more temperamental to environmental changes but
      can be formed without these toxic reagents. In this study, we added a fiber
      reinforcement phase to a poly(vinyl alcohol) (PVA) hydrogel formed through
      successive freezing-thawing cycles by incorporating a non-woven microfiber mat
      formed by the wet-lay process. By reinforcing the hydrogel with a wet-laid
      fibrous mat, the ultimate tensile strength and modulus increased from 0.11 +/-
      0.01 MPa and 0.17 +/- 0.02 kPa to 0.24 +/- 0.02 MPa and 5.76 +/- 1.12 kPa,
      respectively. An increase in toughness and elongation was also found increasing
      from 2.52 +/- 0.37 MPa to 25.6 +/- 3.84 and 51.89 +/- 5.16% to 111.16 +/- 9.68%,
      respectively. The soy fibers were also found to induce minimal cytotoxicity with
      endothelial cell viability showing 96.51% +/- 1.91 living cells after a 48 h
      incubation. This approach to hydrogel-reinforcement presents a rapid, tunable
      method by which hydrogels can attain increased mechanical properties without
      sacrificing their inherent biologically favorable properties.

PMID- 27040225
TI  - Study of photodynamic activity of Au@SiO2 core-shell nanoparticles in vitro.
AB  - Metal-semiconductor core-shell type Au@SiO2 nanoparticles were prepared by
      Stober's method. They were characterized by absorption, XRD, HR-TEM and EDAX
      techniques. The resulting modified core-shell nanoparticles shows that the
      formation of singlet oxygen, which was confirmed by ESR technique. The
      photohemolysis studies were carried out under two different experimental
      conditions. It is observed that the photohemolysis increases with concentration
      as well as light dose. Cell viability of the core-shell nanoparticles against
      HeLa cell lines were studied by MTT assay method. The outcomes of the present
      study indicate that, the Au@SiO2 core-shell nanoparticles are extremely stable
      with a very high photodynamic efficiency under visible light illumination. 

PMID- 27040226
TI  - Purification and functionalization of nanodiamond to serve as a platform for
      amoxicillin delivery.
AB  - Urinary tract infections (UTIs) cost $0.4-0.5 billion a year in the US and is the
      second most common disease affecting millions of people. As resistance to
      antibiotics becomes more common, a greater need for alternative treatments is
      needed. Nanodiamond particles (NDPs) are actively researched as drug delivery
      platforms due to their biocompatibility, particle size, and stable inert core.
      This research is aimed at developing NDPs as antibiotic drug delivery platforms
      for treating UTIs. To this end, 100 nm, 75 nm, 25 nm and 6 nm size NDPs are
      purified with acid and heat treatment techniques. Raman spectra of the NDPs
      showed that the acid treatment method resulted in higher diamond yield. Fourier
      transform infrared spectroscopy (FTIR) studies showed that both purification
      techniques result in oxygen terminated surface groups. Efficiency of loading
      amoxicillin on 25 nm NDPs based on electrostatic interaction of NDPs,
      functionalizing surfaces of NDPs with hydrogen, and polyethylenimine (PEI) are
      investigated. It is found that the electrostatic and surface hydrogenation
      approaches are not efficient in loading amoxicillin on the NDPs. On the other
      hand, PEI functionalized NDPs produced successful loading with amoxicillin as
      indicated by the presence of the beta-lactam peak at 1770 cm(-1), amide peak at
      1680 cm(-1), and bond between PEI NH stretching and amoxicillin -COOH group at
      3650 cm(-1) by the FTIR spectra. These results are expected to lay the foundation
      for developing NDP based targeted drug delivery treatment techniques for treating
      UTIs and other infectious diseases.

PMID- 27040227
TI  - Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide
      coating on titanium surface.
AB  - Owing to its unique physical and chemical properties, graphene oxide (GO) has
      attracted tremendous interest in many fields including biomaterials and
      biomedicine. The purpose of the present study is to investigate the endothelial
      cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium
      surface. To this end, the titanium surface was firstly covered by the
      polydopamine coating followed by the deposition of the GO coating. Heparin was
      finally loaded on the GO coating to improve the blood compatibility. The results
      of attenuated total reflectance Fourier transform infrared spectroscopy (ATR
      FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated
      that the heparin-loaded GO coating was successfully created on the titanium
      surface. The scanning electron microscopy (SEM) images indicated that a relative
      uniform GO coating consisting of multilayer GO sheets was formed on the
      substrate. The hydrophilicity of the titanium surface was enhanced after the
      deposition of GO and further improved significantly by the loading heparin. The
      GO coating can enhance the endothelial cell adhesion and proliferation as
      compared with polydopamine coating and the blank titanium. Loading heparin on the
      GO coating can significantly reduce the platelet adhesion and prolong the
      activated partial thromboplastin time (APTT) while not influence the endothelial
      cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can
      simultaneously enhance the cytocompatibility to endothelial cells and blood
      compatibility of biomaterials. Because the polydopamine coating can be easily
      prepared on most of biomaterials including polymer, ceramics and metal, thus the
      approach of the present study may open up a new window of promising an effective
      and efficient way to promote endothelialization and improve the blood
      compatibility of blood-contact biomedical devices such as intravascular stents. 

PMID- 27040228
TI  - Protective layer formation on magnesium in cell culture medium.
AB  - In the past, different studies showed that hydroxyapatite (HA) or similar calcium
      phosphates can be precipitated on Mg during immersion in simulated body fluids.
      However, at the same time, in most cases a dark grey or black layer is built
      under the white HA crystals. This layer seems to consist as well of calcium
      phosphates. Until now, neither the morphology nor its influence on Mg corrosion
      have been investigated in detail. In this work commercially pure magnesium (cp)
      was immersed in cell culture medium for one, three and five days at room
      temperature and in the incubator (37  degrees C, 5% CO2). In addition, the
      influence of proteins on the formation of a corrosion layer was investigated by
      adding 20% of fetal calf serum (FCS) to the cell culture medium in the incubator.
      In order to analyze the formed layers, SEM images of cross sections, X-ray
      Photoelectron Spectroscopy (XPS), X-ray diffraction (XRD), Energy Dispersive X
      ray Spectroscopy (EDX) and Fourier Transformed Infrared Spectroscopy (FTIR)
      measurements were carried out. Characterization of the corrosion behavior was
      achieved by electrochemical impedance spectroscopy (EIS) and by potentio-dynamic
      polarization in Dulbecco's Modified Eagle's Medium (DMEM) at 37 degrees C.
      Surface analysis showed that all formed layers consist mainly of amorphous
      calcium phosphate compounds. For the immersion at room temperature the Ca/P ratio
      indicates the formation of HA, while in the incubator probably pre-stages to HA
      are formed. The different immersion conditions lead to a variation in layer
      thicknesses. However, electrochemical characterization shows that the layer
      thickness does not influence the corrosion resistance of magnesium. The main
      influencing factor for the corrosion behavior is the layer morphology. Thus,
      immersion at room temperature leads to the highest corrosion protection due to
      the formation of a compact outer layer. Layers formed in the incubator show much
      worse performances due to completely porous structures. The existence of proteins
      in DMEM seems to hinder the formation of a corrosion layer. However, protein
      adsorption leads to similar results as concerns corrosion protection as the
      formed calcium phosphate layer.

PMID- 27040229
TI  - Development and assessment of kerateine nanoparticles for use as a hemostatic
      agent.
AB  - Uncontrolled bleeding frequently occurs in some emergencies which can result in
      severe injury and even death. Keratin hydrogel has been found that it had good
      ahemostatic efficacy in the previous studies. However, an ideal hemostatic agent
      should not require mixing or preparation in advance, and hydrogel is not easy to
      store and carry. In the present study, the kerateine was firstly extracted from
      human hair, and then was prepared nanoparticles by a modified emulsion diffusion
      method. The synthesized nanoparticles showed spherical morphology with an average
      diameter of approximately 200 nm. The results of Fourier transform infrared
      spectroscopy and X-ray diffraction indicated that the chemical structure of
      kerateine did not change but the crystal form may be transformed in the
      nanoparticles. In addition, kerateine nanoparticles displayed a faster clotting
      time in vitro study than the kerateine extracts. Furthermore, kerateine
      nanoparticles significantly reduced the blood loss and coagulation time in the
      liver puncture and tail amputation in rat models. Our results indicated that
      kerateine nanoparticles could quickly form a high viscosity gel onto the wound
      and accelerate the blood coagulation based on their high specific surface area.
      Therefore, kerateine nanoparticles have great potential for hemostatic
      application.

PMID- 27040230
TI  - Effect of cathodic polarization on coating doxycycline on titanium surfaces.
AB  - Cathodic polarization has been reported to enhance the ability of titanium based
      implant materials to interact with biomolecules by forming titanium hydride at
      the outermost surface layer. Although this hydride layer has recently been
      suggested to allow the immobilization of the broad spectrum antibiotic
      doxycycline on titanium surfaces, the involvement of hydride in binding the
      biomolecule onto titanium remains poorly understood. To gain better understanding
      of the influence this immobilization process has on titanium surfaces, mirror
      polished commercially pure titanium surfaces were cathodically polarized in the
      presence of doxycycline and the modified surfaces were thoroughly characterized
      using atomic force microscopy, electron microscopy, secondary ion mass
      spectrometry, and angle-resolved X-ray spectroscopy. We demonstrated that no
      hydride was created during the polarization process. Doxycycline was found to be
      attached to an oxide layer that was modified during the electrochemical process.
      A bacterial assay using bioluminescent Staphylococcus epidermidis Xen43 showed
      the ability of the coating to reduce bacterial colonization and planktonic
      bacterial growth. 

PMID- 27040231
TI  - A novel voltammetric sensor for sensitive detection of mercury(II) ions using
      glassy carbon electrode modified with graphene-based ion imprinted polymer.
AB  - In this paper, a novel strategy was proposed to prepare ion-imprinted polymer
      (IIP) on the surface of reduced graphene oxide (RGO). Polymerization was
      performed using methacrylic acid (MAA) as the functional monomer, ethylene glycol
      dimethacrylate (EGDMA) as the cross-linker, 2,2'-((9E,10E)-1,4
      dihydroxyanthracene-9,10-diylidene) bis(hydrazine-1-carbothioamide) (DDBHCT) as
      the chelating agent and ammonium persulfate (APS) as initiator, via surface
      imprinted technique. The RGO-IIP was characterized by means of Fourier transform
      infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE
      SEM), transmission electron microscopy (TEM) and thermogravimetric analysis
      (TGA). The electrochemical procedure was based on the accumulation of Hg(II) ions
      at the surface of a modified glassy carbon electrode (GCE) with RGO-IIP. The
      prepared RGO-IIP sensor has higher voltammetric response compared to the non
      imprinted polymer (NIP), traditional IIP and RGO. The RGO-IIP modified electrode
      exhibited a linear relationship toward Hg(II) concentrations ranging from 0.07 to
      80 MUg L(-1). The limit of detection (LOD) was found to be 0.02 MUg L(-1)
      (S/N=3), below the guideline value from the World Health Organization (WHO). The
      applicability of the proposed electrochemical sensor to determination of
      mercury(II) ions in different water samples was reported.

PMID- 27040232
TI  - Effect of silver on microstructure and antibacterial property of 2205 duplex
      stainless steel.
AB  - In this study, 2205 duplex stainless steel (DSS) was employed to enhance the
      antibacterial properties of material through silver doping. The results
      demonstrated that silver-doped 2205 DSS produces an excellent bacteria-inhibiting
      effect against Escherichia coli and Staphylococcus aureus. The antibacterial
      rates were 100% and 99.5%, respectively. Because the mutual solubility of silver
      and iron is very low in both the solid and liquid states, a silver-rich compound
      solidified and dispersed at the ferrite/austenite interface and the ferrite,
      austenite, and secondary austenite phases in silver-doped 2205 DSS. Doping 2205
      DSS with silver caused the Creq/Nieq ratio of ferrite to decrease; however, the
      lower Creq/Nieq ratio promoted the rapid nucleation of gamma2-austenite from
      primary alpha-ferrite. After 12h of homogenisation treatment at 1200  degrees C,
      the solubility of silver in the gamma-austenite and alpha-ferrite phases can be
      increased by 0.10% and 0.09%, respectively. Moreover, silver doping was found to
      accelerate the dissolution of secondary austenite in a ferrite matrix during
      homogenisation.

PMID- 27040233
TI  - In situ mineralization of anticancer drug into calcium carbonate monodisperse
      nanospheres and their pH-responsive release property.
AB  - In this paper, we facilitated the preparation of uniform calcium carbonate
      nanospheres and the encapsulation of anticancer drug (Doxorubicin, Dox) in one
      step by a facile bio-inspired mineralization method at room temperature.
      Hesperidin (Hesp), a natural originated flavanone glycoside, was introduced as
      crystallization modifier. The obtained Dox encapsulated CaCO3 nanospheres
      (Dox@CaCO3-Hesp NSs) having a narrow size range of ~200 nm. The drug
      loading/release studies reveal that these Dox@CaCO3-Hesp NSs have a drug loading
      efficiency (DLE) of 83% and drug loading content (DLC) of 14wt%. Besides, the
      release of Dox from Dox@CaCO3-Hesp NSs was pH depended. At pH=7.4, only a small
      amount (~28%) of Dox was released. While at pH=5.0, all amount of incorporated
      Dox was released. Confocal laser scanning microscopy (CLSM) image reveals the
      Dox@CaCO3-Hesp NSs can internalize the cells. These results suggest the Dox@CaCO3
      Hesp NSs can be potentially used to utilize pH-responsive delivery of anticancer
      drugs.

PMID- 27040234
TI  - Curcumin-loaded silica-based mesoporous materials: Synthesis, characterization
      and cytotoxic properties against cancer cells.
AB  - Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous
      materials V3 and V6 were synthesized and characterized by several physico
      chemical techniques. Release kinetic study revealed the slow and sustained
      release of curcumin from those materials in blood simulated fluid (pH: 7.4). The
      materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line
      while exhibiting significant cytotoxicity in different cancer cells (human lung
      carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells:
      B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous
      silica materials based drug delivery systems (DDSs). The generation of
      intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic
      protein leading to the induction of apoptosis were found to be the plausible
      mechanisms behind the anti-cancer activity of these DDSs. These results suggest
      that curcumin-loaded drug delivery system may be successfully employed as an
      alternative treatment strategy for cancer therapeutics through a nanomedicine
      approach in near future. 

PMID- 27040235
TI  - Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal
      route.
AB  - Delivery of drugs to the brain via nasal route has been studied by many
      researchers. However, low residence time, mucociliary clearance and enzymatically
      active environment of nasal cavity pose many challenges to successful nasal
      delivery of drugs. We aim to deliver methotrexate by designing thermosensitive
      nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing
      the blood brain barrier (BBB). PLA nanoparticles were developed using solvent
      evaporation technique. The developed nanoparticles were further dispersed in
      prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the
      property of increased residence time. The formulated nanoparticles demonstrated
      no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and
      erythrocytes which demonstrate the safety of developed formulation for nasal
      administration. The penetration property of nanoparticles though the nasal mucosa
      was higher than the pure drug due to low mucociliary clearance. The developed
      nanoparticles diffused though the membrane pores and rapidly distributed into the
      brain portions compared to the pure drug. There was detectable and quantifiable
      amount of drug seen in the brain as demonstrated by in vivo brain distribution
      studies with considerably low amount of drug deposition in the lungs. The
      pharmacokinetic parameters demonstrated the enhancement in circulation half life,
      area under curve (AUC) and Cmax of the drug when administered intranasal in
      encapsulated form. Thus, the thermosensitive nanodispersions are surely promising
      delivery systems for delivering anticancer agents though the nasal route for
      potential treatment of brain tumors. 

PMID- 27040236
TI  - Material characterization of microsphere-based scaffolds with encapsulated raw
      materials.
AB  - "Raw materials," or materials capable of serving both as building blocks and as
      signals, which are often but not always natural materials, are taking center
      stage in biomaterials for contemporary regenerative medicine. In osteochondral
      tissue engineering, a field leveraging the underlying bone to facilitate
      cartilage regeneration, common raw materials include chondroitin sulfate (CS) for
      cartilage and beta-tricalcium phosphate (TCP) for bone. Building on our previous
      work with gradient scaffolds based on microspheres, here we delved deeper into
      the characterization of individual components. In the current study, the release
      of CS and TCP from poly(D, L-lactic-co-glycolic acid) (PLGA) microsphere-based
      scaffolds was evaluated over a time period of 4 weeks. Raw material encapsulated
      groups were compared to 'blank' groups and evaluated for surface topology,
      molecular weight, and mechanical performance as a function of time. The CS group
      may have led to increased surface porosity, and the addition of CS improved the
      mechanical performance of the scaffold. The finding that CS was completely
      released into the surrounding media by 4 weeks has a significant impact on future
      in vivo studies, given rapid bioavailability. The addition of TCP seemed to
      contribute to the rough external appearance of the scaffold. The current study
      provides an introduction to degradation patterns of homogenous raw material
      encapsulated scaffolds, providing characterization data to advance the field of
      microsphere-based scaffolds in tissue engineering.

PMID- 27040237
TI  - Murine osteoblastic and osteoclastic differentiation on strontium releasing
      hydroxyapatite forming cements.
AB  - Ionic substitutions in hydroxyapatite (HA) scaffolds and self-setting cements
      containing Sr(2+) ions incorporated are particularly of interest in bone
      regeneration. To date, the approach widely used to incorporate Sr(2+) ions into
      HA cements has been the addition of Sr(2+) containing salts, such as SrCO3,
      SrCl2?6H2O, or SrHPO4. However, this approach is dependent upon the relative
      solubility of Sr(2+) containing salts with respect to calcium phosphate (CaP)
      precursors. Therefore, in the current study Sr(2+) substituted dicalcium
      phosphate dihydrate (DCPD) was first synthesized and directly reacted with
      tetracalcium phosphate (TTCP) to form Sr(2+) substituted HA forming cements.
      Rietveld refinement indicated that after one week of aging in phosphate buffered
      saline, cements prepared with and without Sr(2+) were composed of 75% HA and 25%
      unreacted TTCP by weight. Cements prepared with 10% Sr(2+) DCPD exhibited
      increased compressive strengths in comparison to unsubstituted cements. Increased
      MC3T3-E1 proliferation and differentiation were also observed on the cements
      prepared with increasing Sr(2+) content. It was concluded that both the scaffold
      microstructure and Sr(2+) ion release supported osteogenic differentiation. With
      respect to osteoclastic differentiation, no statistically significant differences
      in TRAP activity or cell morphology were observed. This suggests that the amount
      of Sr(2+) released may have been too low to influence osteoclast formation in
      comparison to unsubstituted cements. The results obtained herein demonstrate that
      the use of Sr(2+) substituted DCPD precursors rather than individually separate
      Sr(2+) containing salts may be a useful approach to prepare Sr(2+) containing HA
      cements. 

PMID- 27040238
TI  - Pullulan microcarriers for bone tissue regeneration.
AB  - Microcarrier systems offer a convenient way to repair bone defects as injectable
      cell carriers that can be applied with small incisions owing to their small size
      and spherical shape. In this study, pullulan (PULL) microspheres were fabricated
      and characterized as cell carriers for bone tissue engineering applications. PULL
      was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of
      the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF)
      coating and biomimetic mineralization on the surface by incubating in simulated
      body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and
      fluorescent microscopy analysis confirmed biomimetic mineralization and SF
      coating on microspheres. The degradation analysis revealed that PULL microspheres
      had a slow degradation rate with 8% degradation in two weeks period indicating
      that the microspheres would support the formation of new bone tissue.
      Furthermore, the mechanical tests showed that the microspheres had a high
      mechanical stability that was significantly enhanced with the biomimetic
      mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell
      viability was higher on SF and SBF coated microspheres on 7th day compared to
      PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for
      SF coated microspheres in comparison to uncoated microspheres when dynamic
      culture condition was applied. The results suggest that both organic and
      inorganic surface modifications can be applied on PULL microspheres to prepare a
      biocompatible microcarrier system with suitable properties for bone tissue
      engineering. 

PMID- 27040239
TI  - In vitro and in vivo degradation and mechanical properties of ZEK100 magnesium
      alloy coated with alginate, chitosan and mechano-growth factor.
AB  - The biocompatibility, ultimate loading capacity and biodegradability of magnesium
      alloy make it an ideal candidate in biomedical fields. Fabrications of
      multilayered coatings carrying sodium alginate (ALG), chitosan (CHI) and mechano
      growth factor (MGF) on fluoride-pretreated ZEK100 magnesium alloy have been
      obtained via layer by layer (LBL) to reduce the degradation rate of magnesium
      alloy in this study. The modified surfaces of ZEK100 substrates were
      characterized by scanning electron microscopy (SEM), atomic force microscopy
      (AFM), Fourier transform infrared (FTIR) and CARE EUT-1020 tester. Results reveal
      that multilayer-coated magnesium alloy can be successfully obtained with smooth
      surface morphology, and the mechanical properties of coated samples are almost
      the same as those of uncoated samples. However, the fatigue life of coated ZEK100
      is slightly larger than that of uncoated samples after 1 day of immersion. By
      comparing the degradation of uncoated and multilayer-coated ZEK100 samples in
      vitro and in vivo, respectively, it is found that the degradation rate of ZEK100
      samples can be inhibited by LBL modification on the surface of the sample; and
      the corrosion rate in vivo is lower than that in vitro, which help solve the
      rapid degradation problem of magnesium alloy. In terms of the visible symptom of
      tissues in the left femur medullary cavity and material responses on the surface,
      multilayer-coated ZEK100 magnesium alloy has a good biocompatibility. These
      results indicate that multilayer-coated ZEK100 may be a promising material for
      bone tissue repair.

PMID- 27040240
TI  - Surface characterization and biological evaluation of silver-incorporated DLC
      coatings fabricated by hybrid RF PACVD/MS method.
AB  - Since the biological response of the body towards an implanted material is mainly
      governed by its surface properties, biomaterials are improved by various kinds of
      coatings. Their role is to provide good mechanical and biological
      characteristics, and exclude some disadvantages like post-implantation
      infections. This phenomenon may be reduced by introduction of silver as an
      antibacterial agent. This study evaluates the Ag-DLC films synthesized by the
      hybrid RF PACVD/MS method according to the patent number PL401955-A1 worked out
      inter alia by the authors. Such tests as XPS, SEM, EDS, AFM, FTIR, Raman and ICP
      TOF-MS were used to determine surface properties of the coatings. The obtained
      results were correlated with the biological response estimated on the basis of
      cells viability assay (osteoblast cells line Saos-2) and bacterial colonization
      test (Escherichia coli strain DH5alpha). Results showed that the hybrid RF
      PACVD/MS method allows one to get tight coating preventing the diffusion of
      harmful elements from the metallic substrate. Ag concentration increases with the
      growing power density, it occurs in metallic state, does not create chemical
      bonds and is evenly dispersed within the DLC matrix in the form of nanoscale
      silver clusters. Increasing silver content above 2at.% improves bactericidal
      properties, but decreases cell viability. 

PMID- 27040241
TI  - Micropatterned coculture of hepatocytes on electrospun fibers as a potential in
      vitro model for predictive drug metabolism.
AB  - The liver is the major organ of importance to determine drug dispositions in the
      body, thus the development of hepatocyte culture systems is of great scientific
      and practical interests to provide reliable and predictable models for in vitro
      drug screening. In the current study, to address the challenges of a rapid
      function loss of primary hepatocytes, the coculture of hepatocytes with
      fibroblasts and endothelial cells (Hep-Fib-EC) was established on micropatterned
      fibrous scaffolds. Liver-specific functions, such as the albumin secretion and
      urea synthesis, were well maintained in the coculture system, accompanied by a
      rapid formation of multicellular hepatocyte spheroids. The activities of phase I
      (CYP3A11 and CYP2C9) and phase II enzymes indicated a gradual increase for
      cocultured hepatocytes, and a maximum level was achieved after 5 days and
      maintained throughout 15 days of culture. The metabolism testing on model drugs
      indicated that the scaled clearance rates for hepatocytes in the Hep-Fib-EC
      coculture system were significantly higher than those of other culture methods,
      and a linear regression analysis indicated good correlations between the observed
      data of rats and in vitro predicted values during 15 days of culture. In
      addition, the enzyme activities and drug clearance rates of hepatocytes in the
      Hep-Fib-EC coculture model experienced sensitive responsiveness to the inducers
      and inhibitors of metabolizing enzymes. These results demonstrated the
      feasibility of micropatterned coculture of hepatocytes as a potential in vitro
      testing model for the prediction of in vivo drug metabolism.

PMID- 27040242
TI  - Synthesis of calcium carbonate using extract components of croaker gill as
      morphology and polymorph adjust control agent.
AB  - Biomimetic synthesis of calcium carbonate with various polymorphs, sizes and
      morphologies by using organic substrates has become an interesting topic for the
      last years. Calcium carbonate has been synthesized by the reaction of Na2CO3 and
      CaCl2 in the presence of extract components of croaker gill. The products were
      characterized by powder X-ray diffraction (PXRD) and Fourier transform infrared
      (FT-IR) spectrum, and particle morphologies were observed by scanning electron
      microscope (SEM). The results show that at lower concentration yellow croaker
      gill extract has no effect on calcium carbonate crystal polymorph. Calcite was
      obtained only. But the morphologies of calcite particle change with the increase
      of the concentration. The corners of the particle change from angular to curved.
      However, with the further increase of the concentration of yellow croaker gill
      extract, the calcium carbonate obtained is a mixture of calcite and vaterite. The
      vaterite component in the mixture rises with increasing concentration of extract
      solution, indicating that the proteins from the yellow croaker gill during growth
      play a crucial role in stabilizing and directing the crystal growth. 

PMID- 27040243
TI  - Polyelectrolyte complex of vancomycin as a nanoantibiotic: Preparation, in vitro
      and in silico studies.
AB  - Delivery of antibiotics by various nanosized carriers is proving to be a
      promising strategy to combat limitations associated with conventional dosage
      forms and the ever-increasing drug resistance problem. This method entails
      improving the pharmacokinetic parameters for accumulation at the target infection
      site and reducing their adverse effects. It has been proposed that antibiotic
      nanoparticles themselves are more effective delivery system than encapsulating
      the antibiotic in a nanosystem. In this study, we report on nanoparticles of
      vancomycin (VCM) by self-assembled amphiphilic-polyelectrolyte complexation
      between VCM hydrochloride and polyacrylic acid sodium (PAA). The size,
      polydispersity index and zeta potential of the developed nanoplexes were 229.7 +/
      47.76 nm, 0.442 +/- 0.075, -30.4 +/- 5.3 mV respectively, whereas complexation
      efficiency, drug loading and percentage yield were 75.22 +/- 1.02%, 58.40 +/-
      1.03% and 60.60 +/- 2.62% respectively. An in vitro cytotoxicity study on three
      mammalian cell lines using MTT assays confirmed the biosafety of the newly
      formulated nanoplexes. Morphological investigations using scanning electron
      microscope showed cube shaped hexagonal-like particles. In vitro drug release
      studies revealed that the drug was completely released from the nanoplexes within
      12h. In silico studies revealed that the nano-aggregation was facilitated by
      means of self-association of VCM in the presence of the polymer. The
      supramolecular pattern of the drug self-association was found to be similar to
      that of the VCM dimer observed in the crystal structure of the VCM available in
      Protein Data Bank. In vitro antibacterial activity against susceptible and
      resistant Staphylococcus aureus proved that the potency of VCM was retained after
      being formulated as the nanoplex. In conclusion, VCM nanoplexes could be a
      promising nanodrug delivery system to treat infections of S. aureus origin.

PMID- 27040244
TI  - Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen
      matrix.
AB  - Biomimetic scaffolds with a structural and chemical composition similar to native
      bone tissue may be promising for bone tissue regeneration. In the present work
      hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen
      scaffolds containing an ordered interconnected macroporosity. The mHA were
      obtained by spray drying of a nano hydroxyapatite slurry prepared by the
      precipitation technique. X-ray diffraction (XRD) analysis revealed that the
      microspheres were composed only of hydroxyapatite (HA) phase, and energy
      dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69
      which is near the value for pure HA. The obtained microspheres had an average
      diameter of 6 MUm, a specific surface area of 40 m(2)/g as measured by Brunauer
      Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a
      mesoporous structure with an average pore diameter of 16 nm. Collagen/HA
      microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed
      by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA
      microspheres embedded within a porous collagen matrix with a pore size ranging
      from a few microns up to 200 MUm, which was also confirmed by histological
      staining of sections of paraffin embedded scaffolds. The compressive modulus of
      the composite scaffold at low and high strain values was 1.7 and 2.8 times,
      respectively, that of pure collagen scaffolds. Cell proliferation measured by the
      MTT assay showed more than a 3-fold increase in cell number within the scaffolds
      after 15 days of culture for both pure collagen scaffolds and Col/mHA composite
      scaffolds. Attractive properties of this composite scaffold include the potential
      to load the microspheres for drug delivery and the controllability of the pore
      structure at various length scales.

PMID- 27040245
TI  - The fluoride coated AZ31B magnesium alloy improves corrosion resistance and
      stimulates bone formation in rabbit model.
AB  - This study aimed to evaluate the effect of fluorine coated Mg alloy and clarify
      its mechanism in bone formation. We implanted the fluorine coated AZ31B Mg alloy
      screw (group F) in rabbit mandibular and femur in vivo. Untreated AZ31B Mg alloy
      screw (group A) and titanium screw (group T) were used as control. Then, scanning
      electron microscopy, the spectral energy distribution analysis, hard and
      decalcified bone tissues staining were performed. Immunohistochemistry was
      employed to examine the protein expressions of bone morphogenetic protein 2 (BMP
      2) and collagen type I in the vicinity of the implant. Compared with the group A,
      the degradation of the alloy was reduced, the rates of Mg corrosion and Mg ion
      release were slowed down, and the depositions of calcium and phosphate increased
      in the group F in the early stage of implantation. Histological results showed
      that fluorine coated Mg alloy had well osteogenic activity and biocompatibility.
      Moreover, fluoride coating obviously up-regulated the expressions of collagen
      type I and BMP-2. This study confirmed that the fluorine coating might improve
      the corrosion resistance of AZ31B Mg alloy and promote bone formation by up
      regulated the expressions of collagen type I and BMP-2. 

PMID- 27040246
TI  - Bio-safe processing of polylactic-co-caprolactone and polylactic acid blends to
      fabricate fibrous porous scaffolds for in vitro mesenchymal stem cells adhesion
      and proliferation.
AB  - In this study, the design and fabrication of porous scaffolds, made of blends of
      polylactic-co-caprolactone (PLC) and polylactic acid (PLA) polymers, for tissue
      engineering applications is reported. The scaffolds are prepared by means of a
      bio-safe thermally induced phase separation (TIPS) approach with or without the
      addition of NaCl particles used as particulate porogen. The scaffolds are
      characterized to assess their crystalline structure, morphology and mechanical
      properties, and the texture of the pores and the pore size distribution.
      Moreover, in vitro human mesenchymal stem cells (hMSCs) culture tests have been
      carried out to demonstrate the biocompatibility of the scaffolds. The results of
      this study demonstrate that all of the scaffold materials processed by means of
      TIPS process are semi-crystalline. Furthermore, the blend composition affected
      polymer crystallization and, in turn, the nano and macro-structural properties of
      the scaffolds. Indeed, neat PLC and neat PLA crystallize into globular and
      randomly arranged sub micro-size scale fibrous conformations, respectively.
      Concomitantly, the addition of NaCl particles during the fabrication route allows
      for the creation of an interconnected network of large pores inside the primary
      structure while resulted in a significant decrease of scaffolds mechanical
      response. Finally, the results of cell culture tests demonstrate that both the
      micro and macro-structure of the scaffold affect the in vitro hMSCs adhesion and
      proliferation. 

PMID- 27040247
TI  - Silver nanoparticles-quercetin conjugation to siRNA against drug-resistant
      Bacillus subtilis for effective gene silencing: in vitro and in vivo.
AB  - Quercetin (Qe) exhibited extremely low water solubility, and thus, it was
      modified using silver nanoparticles (AgNPs). We fabricated AgNPs combined with Qe
      (AgNPs-Qe). The modification suggested that the synergistic properties of Qe
      enhanced the antibacterial activity of AgNPs. However, AgNPs-Qe exerted no effect
      on many kinds of drug-resistant bacteria, including Pseudomonas aeruginosa and
      Bacillus subtilis. RNA interference has considerable therapeutic potential
      because of its high specificity and potential capability to evade drug
      resistance. Therefore, we stabilized AgNPs-Qe with a layer of molecules (siRNA).
      The newly fabricated nanoparticles exerted improved effect on many kinds of
      bacteria, including the most prominent drug-resistant species B. subtilis.
      Agarose gel electrophoresis showed that the highest critical nitrogen-to
      phosphorus (N/P) ratio occurred at a vector/siRNA with a w/w ratio of 7:1.
      Characterization experiment indicated that the diameter of siRNA/AgNPs-Qe was
      approximately 40 nm (40 +/- 10 nm). Moreover, AgNPs-Qe were stabilized with a
      layer of siRNA that was approximately 10nm thick. Results of the in vitro study
      suggested that siRNA/AgNPs-Qe could destroy the cell wall and inhibit bacterial
      propagation. Meanwhile, the in vivo experiment on the animal bacteremia model, as
      well as the optical imaging of nude mice and their isolated organs, demonstrated
      that bacteria accumulated in the blood, heart, liver, spleen, lungs, and kidneys
      after the intravenous injection of B. subtilis. The bacteria in the blood and
      organs, as well as the inflamed cells in the tissues, gradually decreased after
      the mice received intravenous tail injection of siRNA/AgNPs-Qe for treatment.
      Both the in vitro and the in vivo studies exhibit that siRNA/AgNPs-Qe can be a
      potential nanoscale drug delivery system for B. subtilis targeting bacterimia.

PMID- 27040248
TI  - Photocurable bioactive bone cement based on hydroxyethyl methacrylate
      poly(acrylic/maleic) acid resin and mesoporous sol gel-derived bioactive glass.
AB  - This paper reports on strong and bioactive bone cement based on ternary bioactive
      SiO2-CaO-P2O5 glass particles and a photocurable resin comprising hydroxyethyl
      methacrylate (HEMA) and poly(acrylic/maleic) acid. The as-cured composite
      represented a compressive strength of about 95 MPa but it weakened during soaking
      in simulated body fluid, SBF, qua its compressive strength reached to about 20
      MPa after immersing for 30 days. Biodegradability of the composite was confirmed
      by reducing its initial weight (~32%) as well as decreasing the molecular weight
      of early cured resin during the soaking procedure. The composite exhibited in
      vitro calcium phosphate precipitation in the form of nanosized carbonated
      hydroxyapatite, which indicates its bone bonding ability. Proliferation of
      calvarium-derived newborn rat osteoblasts seeded on top of the composite was
      observed during incubation at 37  degrees C, meanwhile, an adequate cell
      supporting ability was found. Consequently, it seems that the produced composite
      is an appropriate alternative for bone defect injuries, because of its good cell
      responses, high compressive strength and ongoing biodegradability, though more in
      vivo experiments are essential to confirm this assumption.

PMID- 27040249
TI  - ORMOPLEXEs for gene therapy: In vitro and in vivo assays.
AB  - Gene therapy stays on the cutting edge of biomedical research, being the design
      of the optimal gene delivery vector one of the key requests. Silica-based
      nanoparticles (NPs) have emerged as promising non-viral gene delivery vector, due
      to their high biocompatibility, nontoxicity, non-immunogenicity, biodegradability
      and enormous bioconjugation versatility. In this work a sol-gel methodology for
      the synthesis of amino-functionalized silica NPs (NH2-ORMOSIL NPs) was optimized,
      and NPs were characterized by TEM and FTIR. In a first step NH2-ORMOSIL NPs were
      bioconjugated with a plasmid DNA, pVAX1-GFP, assembling an ORMOPLEXE, confirmed
      by agarose gel electrophoresis. In a second step, in vitro studies have been
      performed with cultured CHO cells, where ORMOPLEXEs transfection was proved by
      CLSM. In vivo transfection efficiency and bio-distribution were performed in
      Zebrafish (Danio rerio) embryos, assessed by FM. Finally, NPs ecotoxicity was
      studied in zebrafish embryos by following the mortality and developmental
      endpoints. 

PMID- 27040250
TI  - Role of triton X-100 and hydrothermal treatment on the morphological features of
      nanoporous hydroxyapatite nanorods.
AB  - Hydroxyapatite (HA) particles were synthesized using Ca(NO3)2.4H2O and (NH4)2HPO4
      as precursors with varying contents of non-ionic surfactant viz., triton X-100
      (organic modifier) via co-precipitation method followed by hydrothermal
      treatment. The prepared HA particles have been characterized by X-ray diffraction
      (XRD), Fourier Transform Infrared spectroscopy (FT-IR), Energy Dispersive X-ray
      Analysis (EDX), High Resolution Scanning Electron Microscopy (HRSEM), High
      Resolution Transmission Electron Microscopy (HRTEM) and Nitrogen adsorption
      desorption experiments. The XRD and FTIR studies indicate the formation of HA
      phase in all the synthesized samples. The specific roles of triton X-100 and
      hydrothermal treatment in dispersing and in directing the crystal growth
      respectively have been discussed by comparing the observations from individual
      experiments using triton X-100 and hydrothermal treatment with that of combined
      protocol involving both. The plausible mechanism for the individual roles of both
      triton X-100 and hydrothermal treatment have been proposed. 

PMID- 27040251
TI  - Development of hybrid cotton/hydrogel yarns with improved absorption properties
      for biomedical applications.
AB  - Hyperhidrosis, or excessive sweating, is an overlooked and potentially disabling
      symptom, which is often seen in social anxiety disorder. In this work an
      innovative advanced textile material was developed for application in the
      management of excessive sweating, preparing a drying yarn providing improved
      comfort. Hybrid cotton/hydrogel yarns were obtained by combining cotton with
      superabsorbent hydrogels through an optimization study focused on the achievement
      of the most promising product in terms of absorption properties and resistance to
      washings. Swelling and washing tests were performed using different hydrogels,
      and the effect of an additional crosslinking on the materials was also evaluated
      by testing different solutions containing Al(3+) and Ca(2+) ions. Scanning
      electron microscopy and infrared spectroscopy analyses were adopted to
      characterize morphology and chemical structure of the hydrogels undergoing
      different production processes. The biocompatibility of the hybrid fabrics was
      demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      colorimetric assay (MTT) through the extract method. 

PMID- 27040252
TI  - Differential pulse voltammetric determination of acyclovir in pharmaceutical
      preparations using a pencil graphite electrode.
AB  - In this study, a new selective and sensitive voltammetric procedure for
      determination of acyclovir (ACV) was proposed using a disposable electrode,
      pencil graphite electrode (PGE). Cyclic and differential pulse voltammograms of
      ACV were recorded in Britton-Robinson buffer solution containing 0.10 M KCl with
      pH of 4.0 at PGE. The PGE displayed a very good electrochemical behavior with
      significant enhancement of the peak current compared to a glassy carbon electrode
      (GCE). Under experimental conditions, the PGE had a linear response range from
      1.0 MUM to 100.0 MUM ACV with a detection limit of 0.3 MUM (based on 3 Sb).
      Relative standard deviations of 4.8 and 3.6% were obtained for five successive
      determinations of 10.0 and 50.0 MUM ACV, respectively, which indicate acceptable
      repeatability. This voltammetric method was successfully applied to the direct
      determination of ACV in real pharmaceutical samples. The effect of various
      interfering compounds on the ACV peak current was studied.

PMID- 27040253
TI  - Precipitation hardening and microstructure evolution of the Ti-7Nb-10Mo alloy
      during aging.
AB  - A biomedical beta titanium alloy (Ti-7Nb-10Mo) was designed and prepared by
      vacuum arc self-consumable melting. The ingot was forged and rolled to plates,
      followed by quenching and aging. Age-hardening behavior, microstructure evolution
      and its influence on mechanical properties of the alloy during aging were
      investigated, using X-ray diffraction, transmission electron microscopy, tensile
      and hardness measurements. The electrochemical behavior of the alloy was
      investigated in Ringer's solution. The microstructure of solution-treated (ST)
      alloy consists of the supersaturated solid solution beta phase and the omegaath
      formed during athermal process. The ST alloy exhibits Young's modulus of 80 GPa,
      tensile strength of 774 MPa and elongation of 20%. The precipitation sequences
      during isothermal aging at different temperatures were determined as
      beta+omegaath->beta+omegaiso (144 h) at Taging=350-400  degrees C, beta+omegaath
      >beta+omegaiso+alpha->beta+alpha at Taging=500 degrees C, and beta+omegaath
      >beta+alpha at Taging=600-650  degrees C, where omegaiso forms during isothermal
      process. The mechanical properties of the alloy can be tailored easily through
      controlling the phase transition during aging. Comparing with the conventional Ti
      6Al-4V alloy, the Ti-7Nb-10Mo alloy is more resistant to corrosion in Ringer's
      solution. Results show that the Ti-7Nb-10Mo alloy is promising for biomedical
      applications.

PMID- 27040254
TI  - The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth:
      Different administration routes.
AB  - The strong anticancer activity of disulfiram is hindered by its rapid degradation
      in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide)
      (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation
      and delivery of disulfiram into breast cancer tumor using passive (EPR effect)
      and active (folate receptor) targeting. The anticancer activity of disulfiram and
      its effect on caspase-3 activity and cell cycle are studied. The administration
      of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor
      routes is investigated using animal model. Disulfiram shows strong cytotoxicity
      against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via
      dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S
      phase time-dependently. The encapsulated disulfiram shows higher activity in
      apoptosis induction as compared to free drug. In nontoxic dose of encapsulated
      disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is
      observed for intravenous injection and intraperitoneal injection. It is suggested
      that administration of disulfiram by targeted PLGA nanoparticles using
      intravenous injection would present an alternative therapeutic approach for solid
      tumor treatment. 

PMID- 27040255
TI  - Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat
      femoral defect.
AB  - Injectable chitosan microparticles were prepared using a simple coacervation
      method under physiologically friendly conditions by eliminating oil or toxic
      chemical, and employing low temperature and pressure for growth factor stability.
      Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the
      chitosan microparticles by two methods: encapsulating and coating techniques.
      These microparticles were tested in vivo to determine the biological response in
      a rat femoral bone defect at 6 and 12 weeks. Four groups (n=10) were tested which
      include two groups for BMP-7 incorporated microparticles (by two techniques),
      microparticles without BMP-7, and defect itself (negative control). Healthy bone
      formation was observed around the microparticles, which were only confined to the
      defect site and did not disperse. Histology indicated minor inflammatory response
      around the microparticles at 6 weeks, which reduced by 12 weeks. Micro-CT
      analysis of bone surface density and porosity was found to be significantly more
      (p<0.05) for microparticles containing groups, in comparison with controls, which
      suggests that the new bone formed in the presence of microparticles is more
      interconnected and porous. Collagen fibrils analysis conducted using multiphoton
      microscopy showed significant improvement in the formation of bundled collagen
      area (%) in microparticles containing groups in comparison with controls,
      indicating higher cross-linking between the fibrils. Microparticles were
      biocompatible and did not degrade in the 12 week implant period.

PMID- 27040256
TI  - Tuning cell adhesion on polymeric and nanocomposite surfaces: Role of topography
      versus superhydrophobicity.
AB  - Development of surface modification procedures which allow tuning the cell
      adhesion on the surface of biomaterials and devices is of great importance. In
      this study, the effects of different topographies and wettabilities on cell
      adhesion behavior of polymeric surfaces are investigated. To this end, an
      improved phase separation method was proposed to impart various wettabilities
      (hydrophobic and superhydrophobic) on polypropylene surfaces. Surface
      morphologies and compositions were characterized by scanning electron microscopy
      and X-ray photoelectron spectroscopy, respectively. Cell culture was conducted to
      evaluate the adhesion of 4T1 mouse mammary tumor cells. It was found that
      processing conditions such as drying temperature is highly influential in cell
      adhesion behavior due to the formation of an utterly different surface
      topography. It was concluded that surface topography plays a more significant
      role in cell adhesion behavior rather than superhydrophobicity since the nano
      scale topography highly inhibited the cell adhesion as compared to the micro
      scale topography. Such cell repellent behavior could be very useful in many
      biomedical devices such as those in drug delivery and blood contacting
      applications as well as biosensors. 

PMID- 27040257
TI  - A simple method for fabrication of electrospun fibers with controlled degree of
      alignment having potential for nerve regeneration applications.
AB  - In peripheral nerve injuries where direct suturing of nerve endings is not
      feasible, nerve regeneration has been facilitated through the use of artificially
      aligned fibrous scaffolds that provide directional growth of neurons to bridge
      the gap. The degree of fiber alignment is crucial and can impact the
      directionality of cells in a fibrous scaffold. While there have been multiple
      approaches that have been used for controlling fiber alignment, however, they
      have been associated with a compromised control on other properties, such as
      diameter, morphology, curvature, and topology of fibers. Therefore, the present
      study demonstrates a modified electrospinning set-up, that enabled fabrication of
      electrospun fibers with controlled degree of alignment from non-aligned (NA),
      moderately aligned (MA, 75%) to highly aligned (HA, 95%) sub-micron fibers while
      keeping other physical properties unchanged. The results demonstrate that the
      aligned fibers (MA and HA) facilitated directional growth of human astrocytoma
      cells (U373), wherein the aspect ratio of cells was found to increase with an
      increase in degree of fibers alignment. In contrast to NA and MA fibers, the HA
      fibers showed improved contact guidance to U373 cells that was demonstrated by a
      significantly higher cell aspect ratio and nuclear aspect ratio. In conclusion,
      the present study demonstrated a modified electrospinning setup to fabricate
      differentially aligned fibrous scaffolds with the HA fibers showing potential for
      use in neural tissue engineering. 

PMID- 27040258
TI  - Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation
      and preliminary in-vitro investigations.
AB  - Carboxymethyl guar gum (CMGG) synthesized from commercially available
      polysaccharide was formulated into nanoparticles via ionic gelation using
      trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using
      a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG
      structure and revealed the effect of the CMGG and STMP concentration on the main
      characteristics of the obtained nanoformulations. The average nanoparticle
      diameter was found to be around 208 nm, as determined by dynamic light scattering
      (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle
      tracking analysis (NTA). Experiments using simulated gastric and intestinal
      fluids evidenced significant pH-dependent drug release behaviour of the
      nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity
      in excess of 83%), as monitored by UV-Vis. While dose-dependent cytotoxicity was
      observed, the nanoformulations appeared completely non-toxic at concentrations
      below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum
      nanoparticles formulated with STMP warrant further investigations as
      polysaccharide based biocompatible drug nanocarriers.

PMID- 27040259
TI  - An electrochemical sensor for rizatriptan benzoate determination using Fe3O4
      nanoparticle/multiwall carbon nanotube-modified glassy carbon electrode in real
      samples.
AB  - In this paper a sensitive and selective electrochemical sensor for determination
      of rizatriptan benzoate (RZB) was proposed. A glassy carbon electrode was
      modified with nanocomposite of multiwalled carbon nanotubes (MWCNTs) and Fe3O4
      nanoparticles (Fe3O4/MWCNTs/GCE). The results obtained clearly show that the
      combination of MWCNTs and Fe3O4 nanoparticles definitely improves the sensitivity
      of modified electrode to RZB determination. The morphology and electroanalytical
      performance of the fabricated sensor were characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction
      (XRD), energy dispersive X-ray spectroscopy (EDS), square wave voltammetry (SWV)
      and cyclic voltammetry (CV). Also, the effect of experimental and instrumental
      parameters on the sensor response was evaluated. The square wave voltammetric
      response of the electrode to RZB was linear in the range 0.5-100.0 MUmol L(-1)
      with a detection limit of 0.09 MUmol L(-1) under the optimum conditions. The
      investigated method showed good stability, reproducibility and repeatability. The
      proposed sensor was successfully applied for real life samples of blood serum and
      RZB determination in pharmaceutical.

PMID- 27040260
TI  - Development of size-customized hepatocarcinoma spheroids as a potential drug
      testing platform using a sacrificial gelatin microsphere system.
AB  - Sacrificial gelatin microspheres can be developed as a cell delivery vehicle for
      non-anchorage dependent cells - its incorporation into a macroscopic scaffold
      system not only allows the cells to be cultured in suspension within cavities
      left behind by the sacrificial material, it also allows scaffold-free tissue
      development to be confined within the cavities. In this study, dense and highly
      viable hepatocarcinoma spheroids were developed by means of encapsulation in
      sacrificial gelatin microspheres produced via a simple water-in-oil emulsion
      technique. By initial selection of microsphere size and distribution, spheroid
      size can be controlled for various applications such as uniform tumor spheroids
      as a reproducible three-dimensional drug screening and testing platform that
      better mimics the in vivo nature of tumors (instead of conventional monolayer
      culture), as this study has suggested as a proof-of-concept with chemotherapy
      drug Doxorubicin. 

PMID- 27040261
TI  - Enzyme mediated synthesis of polypyrrole in the presence of chondroitin sulfate
      and redox mediators of natural origin.
AB  - Polypyrrole (PPy) was synthesized by enzyme mediated oxidation of pyrrole using
      naturally occurring compounds as redox mediators. The catalytic mechanism is an
      enzymatic cascade reaction in which hydrogen peroxide is the oxidizer and soybean
      peroxidase, in the presence of acetosyringone, syringaldehyde or vanillin, acts
      as a natural catalysts. The effect of the initial reaction composition on the
      polymerization yield and electrical conductivity of PPy was analyzed. Morphology
      of the PPy particles was studied by scanning electron microscopy and transmission
      electron microscopy whereas the chemical structure was studied by X-ray
      photoelectron and Fourier transformed infrared spectroscopic techniques. The
      redox mediators increased the polymerization yield without a significant
      modification of the electronic structure of PPy. The highest conductivity of PPy
      was reached when chondroitin sulfate was used simultaneously as dopant and
      template during pyrrole polymerization. Electroactive properties of PPy obtained
      from natural precursors were successfully used in the amperometric quantification
      of uric acid concentrations. PPy increases the amperometric sensitivity of carbon
      nanotube screen-printed electrodes toward uric acid detection. 

PMID- 27040262
TI  - Drug-laden 3D biodegradable label using QR code for anti-counterfeiting of drugs.
AB  - Wiping out counterfeit drugs is a great task for public health care around the
      world. The boost of these drugs makes treatment to become potentially harmful or
      even lethal. In this paper, biodegradable drug-laden QR code label for anti
      counterfeiting of drugs is proposed that can provide the non-fluorescence
      recognition and high capacity. It is fabricated by the laser cutting to achieve
      the roughness over different surface which causes the difference in the gray
      levels on the translucent material the QR code pattern, and the micro mold
      process to obtain the drug-laden biodegradable label. We screened biomaterials
      presenting the relevant conditions and further requirements of the package. The
      drug-laden microlabel is on the surface of the troches or the bottom of the
      capsule and can be read by a simple smartphone QR code reader application.
      Labeling the pill directly and decoding the information successfully means more
      convenient and simple operation with non-fluorescence and high capacity in
      contrast to the traditional methods. 

PMID- 27040263
TI  - A facile microwave synthetic route for ferrite nanoparticles with direct impact
      in magnetic particle hyperthermia.
AB  - The application of ferrite magnetic nanoparticles (MNPs) in medicine finds its
      rapidly developing emphasis on heating mediators for magnetic hyperthermia, the
      ever-promising "fourth leg" of cancer treatment. Usage of MNPs depends largely on
      the preparation processes to select optimal conditions and effective routes to
      finely tailor MNPs. Microwave heating, instead of conventional heating offers
      nanocrystals at significantly enhanced rate and yield. In this work, a facile
      mass-production microwave hydrothermal synthetic approach was used to synthesize
      stable ferromagnetic manganese and cobalt ferrite nanoparticles with sizes
      smaller than 14 nm from metal acetylacetonates in the presence of octadecylamine.
      Prolonging the reaction time from 15 to 60 min, led to ferrites with improved
      crystallinity while the sizes are slight increased. The high crystallinity
      magnetic nanoparticles showed exceptional magnetic heating parameters. In vitro
      application was performed using the human osteosarcoma cell line Saos-2 incubated
      with manganese ferrite nanoparticles. Hyperthermia applied in a two cycle
      process, while AC magnetic field remained on until the upper limit of 45  degrees
      C was achieved. The comparative results of the AC hyperthermia efficiency of
      ferrite nanoparticles in combination with the in vitro study coincide with the
      magnetic features and their tunability may be further exploited for AC magnetic
      hyperthermia driven applications.

PMID- 27040264
TI  - A new titanium based alloy Ti-27Nb-13Zr produced by powder metallurgy with
      biomimetic coating for use as a biomaterial.
AB  - Titanium alloys are widely used in biomedical applications due to their excellent
      properties such as high strength, good corrosion resistance and biocompatibility.
      Titanium alloys with alloying elements such as Nb and Zr are biocompatible and
      have Young's modulus close to that of human bone. To increase the bioactivity of
      titanium alloy surfaces is used chemical treatment with NaOH followed by
      immersion in simulated body fluid (SBF). The purpose of this study was to produce
      the alloy Ti-27Nb-13Zr with low Young's modulus by powder metallurgy using
      powders produced by the HDH process. The formation of biomimetic coatings on
      samples immersed in SBF for 3, 7, 11 and 15 days was evaluated. Characterization
      of the coating was performed by diffuse reflectance infrared Fourier transform
      spectroscopy (DRIFTS) and scanning electron microscope. The microstructure and
      composition of the alloy were determined using SEM and XRD, while the mechanical
      properties were evaluated by determining the elastic modulus and the Vickers
      microhardness. The sintered alloys were composed of alpha and beta phases,
      equiaxed grains and with density around 97.8% of its theoretical density. The
      Vickers microhardness and elasticity modulus of the alloy were determined and
      their values indicate that this alloy can be used as a biomaterial. Analysis of
      the coating revealed the presence of calcium phosphate layers on samples immersed
      for >3 days in the SBF solution.

PMID- 27040265
TI  - Formation of gold decorated porphyrin nanoparticles and evaluation of their
      photothermal and photodynamic activity.
AB  - A core-shell gold (Au) nanoparticle with improved photosensitization have been
      successfully fabricated using Au nanoparticles and 5,10,15,20 tetrakis
      pentafluorophenyl)-21H,23H-porphine (PF6) dye, forming a dyad through molecular
      self-assembly. Au nanoparticles were decorated on the shell and PF6 was placed in
      the core of the nanoparticles. Highly stable Au nanoparticles were achieved using
      PF6 with poly(N-vinylcaprolactam-co-N-vinylimidazole)-g-poly(D,L-lactide) graft
      copolymer hybridization. This was compared with hybridization using
      cetyltrimethylammonium bromide and polyethylene glycol-b-poly(D,L-lactide) for
      shell formation with PF6-Au. The resulting PF6-poly(N-vinylcaprolactam-co-N
      vinylimidazole)-g-poly(D,L-lactide)-Au core-shell nanoparticle were utilized for
      photothermal and photodynamic activities. The spectroscopic analysis and zeta
      potential values of micelles revealed the presence of a thin Au layer coated on
      the PF6 nanoparticle surface, which generally enhanced the thermal stability of
      the gold nanoparticles and the photothermal effect of the shell. The core-shell
      PF6-Au nanoparticles were avidly taken up by cells and demonstrated cellular
      phototoxicity upon irradiation with 300W halogen lamps. The structural
      arrangement of PF6 dyes in the core-shell particles assures the effectiveness of
      singlet oxygen production. The study verifies that PF6 particles when companied
      with Au nanoparticles as PF6-Au have possible combinational applications in
      photodynamic and photothermal therapies for cancer cells because of their high
      production of singlet oxygen and heat.

PMID- 27040266
TI  - Cell growth on 3D microstructured surfaces.
AB  - Chinese Hamster Ovary (CHO) cell cultures were grown on surfaces lithographed
      with periodic 3D hexagonal microcavity array morphology. The range of microcavity
      size (inscribed circle diameter) was from 12 MUm to 560 MUm. CHO cells were grown
      also on flat surfaces. The characterization was performed with respect to cell
      growth density (number of nuclei per unit area) by fluorescence optical
      microscopy and evaluated by correlation function analysis. We found that optimum
      microcavity radius was 80 MUm, concerning to the maximum cell growth density,
      being even greater than the growth density on a flat (unstructured) substrate of
      the same material. This finding can be important for optimization of
      biotechnological processes and devices.

PMID- 27040267
TI  - Corrigendum to "Porous hydrogel of wool keratin prepared by a novel method: An
      extraction with guanidine/2-mercaptoethanol solution followed by a dialysis"
      [Mater. Sci. Eng. C (2014), Volume 42, pp. 146-154].

PMID- 27040268
TI  - ["SOS SEIN 84" accelerated breast disease management: Patients satisfaction
      survey].
AB  - In case of a new breast symptom or an abnormal result of breast imaging, some
      women have a problem finding a quick answer to allay their anxiety. The Institut
      Sainte-Catherine in Avignon has set up a new form of accelerated disease
      management through the opening of a new dedicated consultation called SOS SEIN
      84. We present the result of a prospective quality study of our first new
      patients. 

PMID- 27040269
TI  - Expression of arsenic resistance genes in the obligate anaerobe Bacteroides
      vulgatus ATCC 8482, a gut microbiome bacterium.
AB  - The response of the obligate anaerobe Bacteroides vulgatus ATCC 8482, a common
      human gut microbiota, to arsenic was determined. B. vulgatus ATCC 8482 is highly
      resistant to pentavalent As(V) and methylarsenate (MAs(V)). It is somewhat more
      sensitive to trivalent inorganic As(III) but 100-fold more sensitive to
      methylarsenite (MAs(III)) than to As(III). B. vulgatus ATCC 8482 has eight
      continuous genes in its genome that we demonstrate form an arsenical-inducible
      transcriptional unit. The first gene of this ars operon, arsR, encodes a putative
      ArsR As(III)-responsive transcriptional repressor. The next three genes encode
      proteins of unknown function. The remaining genes, arsDABC, have well
      characterized roles in detoxification of inorganic arsenic, but there are no
      known genes for MAs(III) resistance. Expression of each gene after exposure to
      trivalent and pentavalent inorganic and methylarsenicals was analyzed. MAs(III)
      was the most effective inducer. The arsD gene was the most highly expressed of
      the ars operon genes. These results demonstrate that this anaerobic microbiome
      bacterium has arsenic-responsive genes that confer resistance to inorganic
      arsenic and may be responsible for the organism's ability to maintain its
      prevalence in the gut following dietary exposure to inorganic arsenic. 

PMID- 27040270
TI  - All or nothing: Survival, reproduction and oxidative balance in Spotted Wing
      Drosophila (Drosophila suzukii) in response to cold.
AB  - Winter severity and overwintering capacity are key ecological factors in
      successful invasions, especially in ectotherms. The integration of physiological
      approaches into the study of invasion processes is emerging and promising.
      Physiological information describes the mechanisms underlying observed survival
      and reproductive capacities, and it can be used to predict an organism's response
      to environmental perturbations such as cold temperatures. We investigated the
      effects of various cold treatments on life history and physiological traits of an
      invasive pest species, Drosophila suzukii, such as survival, fertility and
      oxidative balance. This species, a native of temperate Asian areas, is known to
      survive where cold temperatures are particularly harsh and has been recently
      introduced into Europe and North America. We found that cold treatments had a
      strong impact on adult survival but no effect on female's fertility. Although
      only minor changes were observed after cold treatment on studied physiological
      traits, a strong sex-based difference was observed in both survival and
      physiological markers (antioxidant defences and oxidative markers). Females
      exhibited higher survival, reduced oxidative defences, less damage to nucleic
      acids, and more damage to lipids. These results suggest that D. suzukii relies on
      a pathway other than oxidative balance to resist cold injury. Altogether, our
      results provide information concerning the mechanisms of successful invasion by
      D. suzukii. These findings may assist in the development of population models
      that predict the current and future geographic ranges of this species.

PMID- 27040271
TI  - Sequential oogenesis is controlled by an oviduct factor in the locusts Locusta
      migratoria and Schistocerca gregaria: Overcoming the doctrine that patency in
      follicle cells is induced by juvenile hormone.
AB  - In insects that lay eggs in large clutches, yolk accumulation in each of the many
      ovarioles is restricted to the basal (terminal) oocyte, the one closest to the
      lateral oviduct. All succeeding (subterminal) oocytes remain small until the
      terminal oocytes finished their development and were ovulated into the oviduct.
      The major step regulating yolk uptake by terminal oocytes is the formation of
      gaps between cells of the follicle layer, a process termed patency. In the
      migratory as well as in the desert locust, patency is induced by a Patency
      Inducing Factor (PIF) produced by the lateral oviducts. PIF is secreted in all
      regions of the lateral oviducts and interacts with the basal follicle cells via
      the pedicel, a fine duct that connects an ovariole with the oviduct. By this
      mechanism, patency is triggered in the follicle cells of the terminal oocyte
      only, restricting yolk accumulation to the oocytes next to ovulation. In contrast
      to the previous hypothesis, juvenile hormone (JH) is not necessary to induce
      patency, rather JH amplifies the effect of PIF.

PMID- 27040272
TI  - Laparoscopic resection of splenic flexure tumors.
AB  - In this paper a single institution experience in laparoscopic treatment of
      splenic flexure tumors (SFT) is reported. Low incidence of these tumors and
      complexity of the procedure make the laparoscopic resection not diffuse and not
      well standardized. Since 2004, in a specific database, we prospectively record
      clinicopathological features and outcome of all patients submitted to
      laparoscopic colorectal resection. From January 2004 to October 2015, out of 567
      cases of minimally invasive colorectal procedures, we performed 20 laparoscopic
      resection of SFT, 11 with extracorporeal anastomosis and 9 totally laparoscopic.
      Twelve patients had an advanced disease. Conversion rate was null. The mean
      operative time was 105' (range 70'-135'). Comparing extracorporeal and
      intracorporeal anastomoses, we did not find any significant difference in mean
      duration of surgery. Mean distal margin was 9.4 +/- 3.1 cm (mean +/- DS), mean
      proximal margin 8.9 +/- 2.7 cm. The mean number of harvested lymph nodes was 17.8
      +/- 5.6. Evaluating surgical short-term and oncological mid-term outcomes,
      laparoscopic resection of splenic flexure for tumors, even if challenging,
      resulted technically feasible and oncologically safe and it seems to be
      advisable. 

PMID- 27040273
TI  - "Scarless" and no-stoma surgery for low rectal cancer: the laparoscopic pull
      through delayed "high" colo-anal anastomosis.
AB  - Despite recent improvements in surgical technique, low rectal anastomoses for
      rectal cancer still carry a not negligible incidence of anastomotic leakage and
      pelvic related morbidity. The Turnball-Cutait delayed colo-anal anastomosis, also
      referred as pull-through procedure was introduced with the aim to reduce the
      surgical anastomotic related complications and overcome the need of diverting
      ileostomy creation. Recently, this technique regained popularity as a viable
      option not only as salvage procedure after anastomotic failure or in case of
      hostile pelvis but also as first choice option in case of low rectal cancer. We
      report our experience with a personal technique for delayed "high" colo-anal
      anastomosis and its combination with a minimally invasive approach in order to
      reduce surgical morbidity, avoid the need for stoma creation and minimize the
      impact of surgery. Between 2011 and 2015, eight consecutive patients were
      operated for low rectal cancer by the described technique by a minimally invasive
      approach. The procedure was successfully completed in all cases. Post-operative
      major morbidity and 60 days mortality were nihil. There was no need for stoma
      creation or service laparotomy resulting in a virtually "scarless" surgery. Mean
      cumulative hospital stay (combining the two stages of the procedure) was 7, 6
      days (range 7-9). The proposed technique by combining the advantage of a
      minimally invasive approach to those of a delayed "high" colo-anal anastomoses
      can be considered a viable option for the surgical treatment of low rectal
      cancer. 

PMID- 27040274
TI  - Current status of laparoscopic colorectal surgery in the emergency setting.
AB  - Laparoscopic surgery has become well established in the management of both benign
      as malignant colorectal disease. However there has not been the same enthusiasm
      for the use of laparoscopy in emergency colorectal surgery. We have critically
      review the indications and the results of the laparoscopic approach for the
      treatment of acute colorectal disease. A systemic review based on comprehensive
      Literature research was made on Pubmed with the primary objective to identify all
      clinical relevant randomized controlled trials (RCT). However, other reports,
      population based outcomes studies, case series and case reports were also
      included. Cross-link control was than performed with Google Scholar and Cochrane
      library databases. We have reviewed the last years' evident literature about this
      last topic and the results reported , although mainly early, controversial and
      focused on the short term, enabled us to generally conclude that in a proper
      setting, laparoscopic colorectal emergency surgery is feasible, effective, safe
      and beneficial for patients to be a part of a common surgical practice, as long
      as adequate training is obtained and proper preparation observed when more
      advanced procedures are attempted in critically patients. 

PMID- 27040275
TI  - Update on Smoking Cessation: E-Cigarettes, Emerging Tobacco Products Trends, and
      New Technology-Based Interventions.
AB  - Tobacco use disorders (TUDs) continue to be overly represented in patients
      treated in mental health and addiction treatment settings. It is the most common
      substance use disorder (SUD) and the leading cause of health disparities and
      increased morbidity/mortality amongst individuals with a psychiatric disorder.
      There are seven Food and Drug Administration (FDA) approved medications and
      excellent evidence-based psychosocial treatment interventions to use in TUD
      treatment. In the past few years, access to and use of other tobacco or nicotine
      emerging products are on the rise, including the highly publicized electronic
      cigarette (e-cigarette). There has also been a proliferation of technology-based
      interventions to support standard TUD treatment, including mobile apps and web
      based interventions. These tools are easily accessed 24/7 to support outpatient
      treatment. This update will review the emerging products and counter-measure
      intervention technologies, including how clinicians can integrate these tools and
      other community-based resources into their practice. 

PMID- 27040276
TI  - Dendritic cell development-History, advances, and open questions.
AB  - Dendritic cells (DCs) are uniquely potent in orchestrating T cell immune
      response, thus they are indispensable immune sentinels. They originate from
      progenitors in the bone marrow through hematopoiesis, a highly regulated
      developmental process involving multiple cellular and molecular events. This
      review highlights studies of DC development-from the discovery of DCs as glass
      adherent antigen presenting cells to the debate and resolution of their origin
      and lineage map. In particular, we summarize the roles of lineage-specific
      cytokines, the placement of distinct hematopoietic progenitors within the DC
      lineage and transcriptional programs governing DC development, which together
      have allowed us to diagram the current view of DC hematopoiesis. Important open
      questions and debates on the DC development and relevant models are also
      discussed.

PMID- 27040277
TI  - Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High
      Cholesterol Diet.
AB  - Tea dietary fiber (TDF) was prepared from tea residues and modified to get
      cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine
      grinding. The in vitro lipid-binding capacities of the three fibers and their
      effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet
      were evaluated. The results showed that the three fibers had excellent lipid
      binding capacities, and the cholesterol- and sodium cholate-binding capacities of
      CTDF and MTDF were significantly higher than those of TDF. Animal studies showed
      that, compared to model control, the three fibers significantly decreased mice
      average daily gain, gain: feed, and liver index, reduced total cholesterol (TC),
      triglyceride, and low density lipoprotein-cholesterol of serum and liver,
      increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and
      promoted the excretion of fecal lipids, and they also significantly increased the
      activities of superoxide dismutase and glutathione peroxidase of serum and liver,
      and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were
      better than that of TDF. It was concluded that the three fibers could improve
      serum and hepatic lipid profiles in mice fed a high cholesterol diet and the
      mechanism of action might be due to the promotion of fecal excretion of lipids
      through their lipid-binding ability and the inhibition of lipid peroxidation.
      These findings suggest that tea dietary fiber has the potential to be used as a
      functional ingredient to control cardiovascular disease. 

PMID- 27040280
TI  - Announcements for issue 4, 2016.

PMID- 27040278
TI  - Rituximab salvage therapy in adults with immune thrombocytopenia: retrospective
      study on efficacy and safety profiles.
AB  - Splenectomy remains the preferred treatment for chronic immune thrombocytopenia
      (ITP) after corticosteroid failure, despite the risks of despite surgical
      complications and infection. The aim of this study was to assess the efficacy of
      and tolerance to rituximab through a retrospective analysis of 35
      refractory/relapsing ITP patients treated from 2004 to 2013. The median age of
      subjects was 46 years (14-80). Rituximab was given at a weekly dose of 375
      mg/m(2) for 4 weeks. Median time from diagnosis to first infusion was 17 months
      (1-362) and follow-up was 47 months (2-133). The overall response rates at 1 and
      2 years after the first infusion were 47 and 38 %, with complete response rates
      of 24 and 25 %, respectively. Median duration of response was 38 months (1-123),
      with 37 % of patients maintaining a durable response (>1 year). Twenty-nine
      percent of patients had undergone splenectomy. A durable response after rituximab
      was more frequently observed in patients undergoing second-line therapy than
      those in third or later (83 versus 35 %, P = 0.01). Forty-four percent of
      patients experienced mild hypogammaglobulinaemia after rituximab, and no clinical
      infection occurred. To conclude, rituximab should be considered as an alternative
      treatment to splenectomy. Its efficacy and safety profile should lead us to
      choose this medical option therapy before surgery for ITP patients. 

PMID- 27040279
TI  - Intensified and prolonged therapy comprising cytarabine, vincristine and
      prednisolone improves outcome in patients with multisystem Langerhans cell
      histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02
      Protocol Study.
AB  - The JLSG-96 study reported very low mortality rates for children newly diagnosed
      with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was
      performed to further improve the prognosis from 2002 to 2009. The present study
      compared the therapeutic results of these two studies in terms of multisystem
      disease. All patients were treated with 6 weeks of the Induction A regimen,
      comprising cytarabine, vincristine and prednisolone, followed by maintenance
      therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has
      been revised from JLSG-96 in the following respects: prednisolone dosage during
      Induction A increased; duration of maintenance therapy extended from 24 to 48
      weeks; cyclosporine introduced to Induction B for progressive disease. One
      hundred forty-seven children with multisystem LCH were evaluated. Of these, 84
      were positive for risk of organ involvement (RO) and 63 were RO-negative. At the
      6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A.
      Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9]
      for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that
      in JLSG-96 [26.8 % (13.3-40.4) and 38.9 % (16.4-61.4), respectively]. The
      intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS
      in patients with multisystem LCH. 

PMID- 27040281
TI  - Confirmatory factor analysis of the neck disability index, comparing patients
      with whiplash associated disorders to a control group with non-specific neck
      pain.
AB  - Purpose The neck disability index (NDI) as a 10-item patient reported outcome
      (PRO) measure is the most commonly used whiplash associated disorders (WAD)
      assessment tool. However, statistical rigor and factor structure are not
      definitive. To date, confirmatory factor analysis (CFA) has not examined whether
      the factor structure generalizes across different groups (e.g., WAD versus non
      WAD). This study aimed to determine the psychometric properties of the NDI in
      these population groups. METHODS: This study used CFA to analyze NDI baseline
      data for WAD (n = 804; 69 % females) and non-WAD (n = 963; 67 % females), each
      for the full sample and separate genders. Invariance analyses examined the NDI
      structure across the four groups. RESULTS: Across both populations and gender
      subgroups the one-factor solutions consistently showed better model fit over two
      factor solutions. The NDI was best characterized as one-dimensional and invariant
      across multiple sub-groups. CONCLUSION: The NDI remains a valid PRO in WAD
      populations that provides acceptable measurement of neck status that is
      appropriate for basic functional assessment across genders. However, it is
      recommended that both clinicians and researchers initiate the transition toward
      more rigorous and less ambiguous PRO measurement tools for WAD patients and
      research. This future graduated movement toward other PROs should consider both
      regional PROs and computerized decision support systems, initially measured
      concurrently with the NDI to establish ways to convert existing scored data prior
      to their singular use.

PMID- 27040283
TI  - Leukocyte Infiltration Triggers Seizure Recurrence in a Rat Model of Temporal
      Lobe Epilepsy.
AB  - Epilepsy, which affects about 1 % of the population worldwide, leads to poor
      prognosis and increased morbidity. However, effective drugs providing
      satisfactory control on seizure relapse were rare, which encouraged more
      etiological studies. Whether inflammation is one of key events underlying seizure
      is in debate. In order to explore the role of inflammatory in the pathogenesis
      and development of epilepsy, we conducted intra-caudal vein injection of
      leukocytes to aggravated brain inflammatory process in kainic acid-induced
      seizure model in this study. The results showed that intravenous administration
      of activated leukocytes increased the frequency and reduced the latent phase of
      seizure recurrences in rat models of epileptic seizure, during which leukocyte
      inflammation, brain-blood barrier damage, and neuron injury were also
      significantly aggravated, indicating that leukocyte infiltration might facilitate
      seizure recurrence through aggravating brain inflammation, brain-blood barrier
      damage, and neuron injury. 

PMID- 27040284
TI  - Effects of adrenaline on circulatory dynamics and cardiac function in rats
      administered chlorpromazine.
AB  - We aimed to elucidate changes in circulatory dynamics and cardiac function during
      concomitant use of chlorpromazine (CPZ) and adrenaline (AD). An arterial line and
      left intraventricular pressure-volume measurement catheter were inserted in rats.
      CPZ 10 mg/kg was administered to the left great adductor muscle, followed by
      normal saline (NS) or AD 50 MUg/kg through the tongue 20 min later. End-diastolic
      volume (V ed), end-systolic pressure (P es), stroke volume (SV), stroke work
      (SW), end-systolic volume elastance (E es), systolic blood pressure (SBP),
      diastolic blood pressure (DBP), and pulse rate (PR) were measured. Following AD
      administration, V ed significantly decreased at 2-4 and 10 min than that in
      control rats; P es significantly decreased at 1 min; E es significantly increased
      from 2 to 10 min; SV did not change significantly, and SW significantly reduced
      at 1 and 2 min; SBP and DBP were lower at 1-3 min than in the control; and PR
      increased at 10 min. These findings suggest that when AD-containing local
      anesthetics are administered during dental treatment of patients taking CPZ,
      there is a risk of a temporary drop in blood pressure. However, the blood
      pressure is recovered a few minutes later by the increase in afterload and the
      myocardial contractile force.

PMID- 27040286
TI  - Emergency Drugs for the Dental Office.
AB  - Any dental office can face a variety of medical emergencies; therefore, the
      health care professional and the staff should always be prepared to deal with
      these emergencies in their office. Preparedness of the dental office staff and
      their prompt recognition of these emergencies will be the most important factor
      in dealing with the emergencies in any dental office. Health care professionals
      should follow the recommendations in this article to maintain a guideline for
      their staff and office and conduct regular emergency drills to examine the
      equipment and preparedness of their staff. 

PMID- 27040285
TI  - Risk stratification of childhood medulloblastoma in the molecular era: the
      current consensus.
AB  - Historical risk stratification criteria for medulloblastoma rely primarily on
      clinicopathological variables pertaining to age, presence of metastases, extent
      of resection, histological subtypes and in some instances individual genetic
      aberrations such as MYC and MYCN amplification. In 2010, an international panel
      of experts established consensus defining four main subgroups of medulloblastoma
      (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has
      led to the current generation of biomarker-driven clinical trials assigning WNT
      tumors to a favorable prognosis group in addition to clinicopathological criteria
      including MYC and MYCN gene amplifications. However, outcome prediction of non
      WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a
      consensus conference was convened in Heidelberg with the objective to further
      refine the risk stratification in the context of subgroups and agree on a
      definition of risk groups of non-infant, childhood medulloblastoma (ages 3-17).
      Published and unpublished data over the past 5 years were reviewed, and a
      consensus was reached regarding the level of evidence for currently available
      biomarkers. The following risk groups were defined based on current survival
      rates: low risk (>90 % survival), average (standard) risk (75-90 % survival),
      high risk (50-75 % survival) and very high risk (<50 % survival) disease. The WNT
      subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole
      chromosome 17 gain were recognized as low-risk tumors that may qualify for
      reduced therapy. High-risk strata were defined as patients with metastatic SHH or
      Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients
      are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of
      consensus points were reached that should be standardized across future clinical
      trials. Although we anticipate new data will emerge from currently ongoing and
      recently completed clinical trials, this consensus can serve as an outline for
      prioritization of certain molecular subsets of tumors to define and validate risk
      groups as a basis for future clinical trials.

PMID- 27040287
TI  - Oral Sedation in the Dental Office.
AB  - This article highlights the commonly used medications used in dentistry and oral
      surgery. General dentists and specialists must be knowledgeable about the
      pharmacology of the drugs currently available along with their risks and
      benefits. Enteral sedation is a useful adjunct for the treatment of anxious adult
      and pediatric patients. When enteral sedation is used within the standards of
      care, the interests of the public and the dental profession are served through a
      cost-effective, effective service that can be widely available. Oral sedation
      enables dentists to provide dental care to millions of individuals who otherwise
      would have unmet dental needs. 

PMID- 27040288
TI  - Conscious Intravenous Sedation in Dentistry: A Review of Current Therapy.
AB  - Several sedation options are used to minimize pain, anxiety, and discomfort
      during oral surgery procedures. Minimizing or eliminating pain and anxiety for
      dental care is the primary goal for conscious sedation. Intravenous conscious
      sedation is a drug-induced depression of consciousness during which patients
      respond purposefully to verbal commands. No interventions are required to
      maintain a patent airway, and spontaneous ventilation is adequate as well as
      cardiovascular function. Patients must retain their protective airway reflexes,
      and respond to and understand verbal communication. The drugs and techniques used
      must therefore carry a broad margin of safety. 

PMID- 27040289
TI  - Update on Analgesic Medication for Adult and Pediatric Dental Patients.
AB  - This article is an update on pain management in the dental care setting for adult
      and pediatric patients. The 3 main categories of analgesic medications are
      examined: (1) opioids, (2) nonsteroidal antiinflammatory drugs (NSAIDs), and (3)
      nonopioid, non-NSAID medications. Pharmacology, side effects, patient selection,
      and treatment strategies and principles are examined. The information provided is
      aimed to facilitate the clinical perspective and update the oral health care
      clinician on providing safe and effective analgesia to adult and pediatric
      patients. 

PMID- 27040290
TI  - Pharmacologic Treatment for Temporomandibular Disorders.
AB  - Pharmacologic agents play an integral role in the overall management of
      temporomandibular joint disorder. The general dentist should be familiar with the
      different classes of drugs currently in use for dealing with this often complex
      medical/dental problem. 

PMID- 27040291
TI  - Orofacial Pain: Pharmacologic Paradigms for Therapeutic Intervention.
AB  - Pain is a universal experience with profound effects on the physiology,
      psychology, and sociology of the population. Orofacial pain (OFP) conditions are
      especially prevalent and can be severely debilitating to a patient's health
      related quality of life. Evidence-based clinical trials suggest that
      pharmacologic therapy may significantly improve patient outcomes either alone or
      when used as part of a comprehensive treatment plan for OFP. The aim of this
      article is to provide therapeutic options from a pharmacologic perspective to
      treat a broad spectrum of OFP. Clinical-based systemic and topical applied
      pharmaceutical approaches are presented to treat the most common OFP syndromes. 

PMID- 27040292
TI  - The Pharmacologic Management of Common Lesions of the Oral Cavity.
AB  - The oral ulcerations caused by aphtous lesions, herpetic lesions, candidiasis,
      ulcerative lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris are
      managed in a step-up approach that can involve topical, intarlesional, and
      systemic pharmacologic management. This article reviews the common treatment
      agents, modalities, and dosages. The emphasis is on local pharmacologic
      therapies, yet systemic conditions that often present with such oral lesions are
      briefly reviewed, along with the appropriate management. 

PMID- 27040293
TI  - Review of Top 10 Prescribed Drugs and Their Interaction with Dental Treatment.
AB  - The proportion of people over age 60 is growing faster than any other group. Many
      patients take several medications to manage multiple chronic medical conditions.
      Poor oral health is common and dental visits by patients over the age of 65 are
      increasing. The dentist must recognize that these medications may interact with
      dental treatment. This article reviews the top 10 prescribed drugs as listed in
      the IMS Institute national prescription audit in January 2015 and reviews the
      interactions between these medications and dental treatment. The medications
      reviewed include levothyroxine, acetaminophen/hydrocodone, lisinopril,
      metoprolol, atorvastatin, amlodipine, metformin, omeprazole, simvastatin, and
      albuterol. 

PMID- 27040294
TI  - Hyposalivation and Xerostomia: Etiology, Complications, and Medical Management.
AB  - Saliva is one of the most versatile, multifunctional substances produced by the
      body and has a critical role in the preservation of the oropharyngeal health. It
      comprises a serous and mucinous component and is secreted by the major salivary
      glands. The mucins in the saliva serve to protect and lubricate the hard and soft
      tissues of the mouth, protecting them from chemical and mechanical damage.
      Hyposalivation can be managed by various salivary substitutes, peripheral
      sialagogues, and central sialagogues. 

PMID- 27040295
TI  - Updates of Topical and Local Anesthesia Agents.
AB  - As described in this article, there are many advances in topical and local
      anesthesia. Topical and local anesthetics have played a great role in dentistry
      in alleviating the fears of patients, eliminating pain, and providing pain
      control. Many invasive procedures would not be performed without the use and
      advances of topical/local anesthetics. The modern-day dentist has the
      responsibility of knowing the variety of products on the market and should have
      at least references to access before, during, and after treatment. This practice
      ensures proper care with topical and local anesthetics for the masses of patients
      entering dental offices worldwide. 

PMID- 27040296
TI  - Current Concepts of Prophylactic Antibiotics for Dental Patients.
AB  - Despite numerous guidelines, joint interprofessional collaboration, and years of
      data collection, the use of antibiotic prophylaxis before dental procedures
      remains controversial. There continues to be disagreement on indications,
      justification, and outcome of the use of various antibiotic prophylaxis
      regiments. This is complicated by the lack of data demonstrating any positive or
      negative impact on the care of patients. The dental community has distanced
      itself from a leadership role in this conversation, based on multiple concerns
      including fear of litigation, lack of clear pathophysiology, and unclear cause
      effect relationship. 

PMID- 27040297
TI  - Medication Management of Jaw Lesions for Dental Patients.
AB  - Most pathologic lesions of the jaws or of oral mucosa are treated successfully by
      surgical interventions. For treatment of the central giant cell lesion,
      aneurysmal bone cysts, histiocytosis of the mandible, hemangioma, odontogenic
      keratocyst, Paget disease, oral submucous fibrosis, and oral lichen planus,
      medical management consisting of intralesional injections, sclerosing agents, and
      systemic bisphosphonates is as successful as surgical procedures with fewer
      complications. Pharmacology of agents used and protocols are presented. 

PMID- 27040298
TI  - Antimicrobial Therapy in Management of Odontogenic Infections in General
      Dentistry.
AB  - This article focuses on the diagnosis and management of odontogenic infections.
      Current antibiotic regimens are reviewed and discussed including use of
      alternative antibiotics with patients known to have a penicillin allergy.
      Emphasis is made on proper examination of the patient with use of diagnostic aids
      to provide the correct treatment of choice. 

PMID- 27040299
TI  - Botulinum Toxin Type A: Review and Its Role in the Dental Office.
AB  - For the general dentist, the use of botulinum toxin type A (BTA) confers the
      ability to exert control over the soft tissues surrounding the mouth to better
      create a harmonious smile. The injection of BTA into the facial musculature
      requires a level of finesse to achieve the desired outcomes. A sound
      understanding of the toxin's mechanism of action and the ability to manage
      potential complications are also necessary, as the dentist administering BTA must
      be competent to the same level as other providers who have traditionally been the
      gatekeepers of such agents. 

PMID- 27040300
TI  - Medication for Gravid and Nursing Dental Patients.
AB  - The topics the authors address in this article are in many ways both broad and
      narrow. The broadness of this topic is clear when one considers the intersection
      of 2 of the more complex areas in medicine: pharmacology and obstetrics. Many of
      the common drugs used by dentists have been found to be safe for breastfeeding
      women; however, consultation with the treating physician may be needed. 

PMID- 27040301
TI  - Medications to Assist in Tobacco Cessation for Dental Patients.
AB  - Smoking is the leading cause of preventable illness in the United States. Without
      assistance, only 3% to 6% of smokers successfully quit after 1 year. Nicotine
      replacement therapy (NRT), buproprion, and varenicline are first-line
      pharmacologic therapies. These medications function by reducing nicotine
      withdrawal symptoms and the desire to smoke. When first-line therapy does not
      lead to successful smoking cessation, combinations of varenicline with NRT,
      buproprion with NRT, and varenicline with buproprion may be efficacious.
      Behavioral therapy also plays a role in smoking cessation and the combination of
      pharmacologic therapy with behavioral therapy is more effective than either
      therapy alone. 

PMID- 27040302
TI  - Clinical Pharmacology for Dentists.

PMID- 27040303
TI  - Mycoplasma pneumoniae-Induced Mucocutaneous Rash: A New Syndrome Distinct from
      Erythema Multiforme? Report of a New Case and Review of the Literature.
AB  - Respiratory tract infection due to Mycoplasma pneumoniae can provoke cutaneous
      and mucosal rashes, which have been classified within the spectrum of erythema
      multiforme or Stevens-Johnson syndrome. This classification is of therapeutic and
      prognostic importance and has generated intense debate in the literature. A
      recent systematic review of 202 cases of mucocutaneous rashes associated with M.
      pneumoniae infection concluded that these rashes might constitute a distinct
      entity, for which the term Mycoplasma-induced rash and mucositis was proposed. We
      describe a patient with acute M pneumoniae respiratory tract infection who
      presented mucosal and cutaneous lesions that were difficult to classify as
      erythema multiforme or Stevens-Johnson syndrome; the lesions were compatible with
      the proposed new disease. 

PMID- 27040304
TI  - Gender differences in antibiotic prescribing in the community: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: Determinants of inappropriate antibiotic prescription in the
      community are not clearly defined. The objective of this study was to perform a
      systematic review and meta-analysis evaluating gender differences in antibiotic
      prescribing in primary care. METHODS: All studies analysing antibiotic
      prescription in primary care were eligible. PubMed and MEDLINE entries with
      publication dates from 1976 until December 2013 were searched. The primary
      outcomes were the incidence rate ratio (IRR) (measured as DDD/1000
      inhabitants/day) and the prevalence rate ratio (PRR) (measured as prevalence
      rate/1000 inhabitants) of antimicrobial prescription, stratified by gender, age
      and antibiotic class. Random-effects estimates of the IRR and PRR and standard
      deviations were calculated. RESULTS: Overall, 576 articles were reviewed. Eleven
      studies, comprising a total of 44 333 839 individuals, were included. The studies
      used data from prospective national (five studies) or regional (six studies)
      surveillance of community pharmacy, insurance or national healthcare systems.
      Women were 27% (PRR 1.27 +/- 0.12) more likely than men to receive an antibiotic
      prescription in their lifetimes. The amount of antibiotics prescribed to women
      was 36% (IRR 1.36 +/- 0.11) higher than that prescribed for men in the 16 to 34
      years age group and 40% (IRR 1.40 +/- 0.03) greater in the 35 to 54 years age
      group. In particular, the amounts of cephalosporins and macrolides prescribed to
      women were 44% (IRR 1.44 +/- 0.30) and 32% (IRR 1.32 +/- 0.15) higher,
      respectively, than those prescribed for men. CONCLUSIONS: This meta-analysis
      shows that women in the 16 to 54 years age group receive a significantly higher
      number of prescriptions of cephalosporins and macrolides in primary care than men
      do. Prospective studies are needed to address reasons for gender inequality in
      prescription and to determine whether a difference in adverse events, including
      resistance development, also occurs.

PMID- 27040305
TI  - NIR-NIR fluorescence: A new genre of fingermark visualisation techniques.
AB  - A preliminary study reveals that finely divided cuprorivaite powder may be used
      to efficiently develop and subsequently image latent fingermarks across a range
      of highly patterned, coloured non-porous and semi-porous substrates using near
      infrared illumination and imaging. Problematic multi-coloured backgrounds provide
      very little interference under the illumination conditions used, and invoked
      fluorescence observed, when using this material. This is the first reported
      example of a NIR-NIR fluorophore for use within latent fingermark visualisation
      and offers the potential for application at the scene and in the laboratory. 

PMID- 27040306
TI  - TRAF3IP2 mediates aldosterone/salt-induced cardiac hypertrophy and fibrosis.
AB  - Aberrant activation of the renin-angiotensin-aldosterone system (RAAS)
      contributes to adverse cardiac remodeling and eventual failure. Here we
      investigated whether TRAF3 Interacting Protein 2 (TRAF3IP2), a redox-sensitive
      cytoplasmic adaptor molecule and an upstream regulator of nuclear factor-kappaB
      (NF-kappaB) and activator protein-1 (AP-1), mediates aldosterone-induced cardiac
      hypertrophy and fibrosis. Wild type (WT) and TRAF3IP2-null mice were infused with
      aldosterone (0.2 mg/kg/day) for 4 weeks along with 1%NaCl in drinking water.
      Aldosterone/salt, but not salt alone, upregulated TRAF3IP2 expression in WT mouse
      hearts. Further, aldosterone elevated blood pressure to a similar extent in both
      WT and TRAF3IP2-null groups. However, TRAF3IP2 gene deletion attenuated
      aldosterone/salt-induced (i) p65 and c-Jun activation, (ii) extracellular matrix
      (collagen Ialpha1 and collagen IIIalpha1), matrix metalloproteinase (MMP2), lysyl
      oxidase (LOX), inflammatory cytokine (IL-6 and IL-18), chemokine (CXCL1 and
      CXCL2), and adhesion molecule (ICAM1) mRNA expression in hearts, (iii) IL-6, IL
      18, and MMP2 protein levels, (iv) systemic IL-6 and IL-18 levels, and (iv)
      cardiac hypertrophy and fibrosis. These results indicate that TRAF3IP2 is a
      critical signaling intermediate in aldosterone/salt-induced myocardial
      hypertrophy and fibrosis, and thus a potential therapeutic target in hypertensive
      heart disease.

PMID- 27040307
TI  - P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in
      neuronal cells.
AB  - P21-activated kinases (PAKs) are recently reported as important players of
      insulin signaling and glucose homeostasis in tissues like muscle, pancreas and
      liver. However, their role in neuronal insulin signaling is still unknown.
      Present study reports the involvement of PAK2 in neuronal insulin signaling,
      glucose uptake and insulin resistance. Irrespective of insulin sensitivity,
      insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked
      enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2
      over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin
      suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose
      uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of
      PP2A resulted in increased PAK2 activity, with corresponding changes in glucose
      uptake. Taken together, present study demonstrates an inhibitory role of insulin
      signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1
      dependent negative regulator of neuronal glucose uptake and insulin sensitivity.

PMID- 27040308
TI  - Pregnancy and lactation differentially modify the transcriptional regulation of
      steroidogenic enzymes through DNA methylation mechanisms in the hippocampus of
      aged rats.
AB  - In the present study, we examined the mRNA expression and DNA methylation state
      of steroidogenic enzymes in the hippocampus of young adult (90-days-old) and
      middle-aged (450-days-old) nulliparous rats, and middle-aged multiparous rats
      subjected to three pregnancies with and without lactation. Aging decreased the
      mRNA levels of steroidogenic-related genes, while pregnancy and lactation
      significantly reduced the effect of aging, maintaining high expression levels of
      cytochrome P450 side-chain cleavage (P450scc), steroid 5alpha-reductase-1
      (5alphaR-1), cytochrome P450arom (P450arom) and aldosterone synthase
      (P450(11beta)-2). In addition, pregnancy and lactation diminished the methylation
      state of the 5alphaR-1 promoter and increased the transcription of brain-derived
      neurotrophic factor, synaptophysin and spinophilin. Pregnancy without lactation
      increased P450scc and 5alphaR-1 gene expression and decreased the methylation of
      their promoters. We concluded that the age-related decrease in the mRNA
      expression of steroidogenic enzymes is differentially attenuated by pregnancy and
      lactation in the rat hippocampus and that differential methylation mechanisms
      could be involved.

PMID- 27040312
TI  - Excessive red and processed meat intake: relations with health and environment in
      Brazil.
AB  - The aims of the present study were to verify the proportion of population that
      consumed more red and processed meat than the World Cancer Research Fund (WCRF)
      dietary recommendation, to estimate the environmental impact of beef intake and
      the possible reduction of greenhouse gas emissions if the dietary recommendation
      was followed. We used the largest, cross-sectional, population-based survey
      entitled the National Dietary Survey (34 003 participants aged 10-104 years). The
      usual meat intake was obtained by two food records completed on 2 non-consecutive
      days. The usual intake was estimated by the multiple source method. The
      environmental impact was analysed according to estimates of CO2 equivalent
      emissions from beef intake as a proxy for beef production in Brazil. The red and
      processed meat intake mean was 88 g/d. More than 80 % of the population consumed
      more red and processed meat than the WCRF recommendation. Beef was the type of
      meat most consumed, accounting to almost 50 %. Each person contributed 1005 kg of
      CO2 equivalents from beef intake in 2008, the same quantity of CO2 produced if a
      car travelled a distance between the extreme north and south of Brazil (5370 km).
      The entire Brazilian population contributed more than 191 million tons of CO2
      equivalents, which could have been reduced to more than 131 million tons if the
      dietary recommendation was followed. The present study shows that the magnitude
      of the excessive red and processed meat intake in Brazil can impact on health and
      the environment, pointing to the urgency of promoting a sustainable diet.

PMID- 27040313
TI  - Gardasil-9: A global survey of projected efficacy.
AB  - Human papillomaviruses (HPVs) are the causative agents of human neoplasias such
      as warts and cancers. There are ~19 HPV types associated with cancers, which has
      made it very challenging for first generation HPV vaccines to offer complete
      protection against all cancer-causing HPV types. Recently, a second generation
      HPV vaccine, Gardasil-9, has been approved to protect against more HPV types.
      Worldwide, Gardasil-9 will protect against HPV types associated with ~90% of
      cervical cancer case in women and 80-95% of other HPV-associated anogenital
      cancers in both men and women. However, due to variation in HPV-type specific
      prevalence and distribution, the vaccine will offer different percentages of
      protection in different geographical regions; Gardasil-9 will offer protection
      against HPV types associated with ~87.7% of cervical cancers in Asia, 91.7% in
      Africa, 92% in North America, 90.9% in Europe, 89.5% in Latin America & the
      Caribbean, and 86.5% in Australia. Because of this, Pap smear screening and
      testing for HPV types not included in Gardasil-9 will need to continue,
      especially in HIV/AIDS patients. In order to achieve complete protection against
      all HPV types that cause cervical cancer, a third-generation HPV vaccine is
      needed.

PMID- 27040314
TI  - Antiviral effect of resveratrol in ducklings infected with virulent duck
      enteritis virus.
AB  - Duck enteritis virus (DEV) is a double-stranded DNA virus belonging to the
      alphaherpesvirinae subfamily of the herpesviridae. Although vaccines were wildly
      used in controlling this disease, some infection could still not be prevented and
      led to significant economic losses as a result of mortality and decreased egg
      production. However, there is no antiviral drug against DEV. Resveratrol was
      identified to exert its antiviral activity by inhibiting the DEV replication in
      preliminary investigations. In the present study, we confirmed that resveratrol
      significantly reduced the mortality of ducklings which infected with a virulent
      strain of DEV. With resveratrol treatment, the survival rate increased by almost
      80% at 8 days post infection (dpi). Pathological symptoms of ducklings caused by
      DEV were also relieved by resveratrol. The virus load in blood and tissues were
      effectively depressed when compared with the untreated group. In the assay of
      immune cytokines, the resveratrol exerted a dual-regulation effect. These results
      suggest that resveratrol is expected to be a new alternative control measure for
      DEV infection.

PMID- 27040315
TI  - Recent Progress on Ferroelectric Polymer-Based Nanocomposites for High Energy
      Density Capacitors: Synthesis, Dielectric Properties, and Future Aspects.
AB  - Dielectric polymer nanocomposites are rapidly emerging as novel materials for a
      number of advanced engineering applications. In this Review, we present a
      comprehensive review of the use of ferroelectric polymers, especially PVDF and
      PVDF-based copolymers/blends as potential components in dielectric nanocomposite
      materials for high energy density capacitor applications. Various parameters like
      dielectric constant, dielectric loss, breakdown strength, energy density, and
      flexibility of the polymer nanocomposites have been thoroughly investigated.
      Fillers with different shapes have been found to cause significant variation in
      the physical and electrical properties. Generally, one-dimensional and two
      dimensional nanofillers with large aspect ratios provide enhanced flexibility
      versus zero-dimensional fillers. Surface modification of nanomaterials as well as
      polymers adds flavor to the dielectric properties of the resulting
      nanocomposites. Nowadays, three-phase nanocomposites with either combination of
      fillers or polymer matrix help in further improving the dielectric properties as
      compared to two-phase nanocomposites. Recent research has been focused on
      altering the dielectric properties of different materials while also maintaining
      their superior flexibility. Flexible polymer nanocomposites are the best
      candidates for application in various fields. However, certain challenges still
      present, which can be solved only by extensive research in this field. 

PMID- 27040316
TI  - Role of Amphiphilic Block Copolymer Composition on Pore Characteristics of
      Micelle-Templated Mesoporous Cobalt Oxide Films.
AB  - Block copolymer templating is a versatile approach for the generation of well
      defined porosity in a wide variety of framework chemistries. Here, we
      systematically investigate how the composition of a poly(methoxy poly[ethylene
      glycol] methacrylate)-block-poly(butyl acrylate) (PMPEG-PBA) template impacts the
      pore characteristics of mesoporous cobalt oxide films. Three templates with a
      constant PMPEG segment length and different hydrophilic block volume fractions of
      17%, 51%, and 68% for the PMPEG-PBA are cooperatively assembled with cobalt
      nitrate hexahydrate and citric acid. Irrespective of template composition, a
      spherical nanostructure is templated and elliptical mesostructures are obtained
      on calcination due to uniaxial contraction of the film. The average pore size
      increases from 11.4 +/- 2.8 to 48.5 +/- 4.3 nm as the length of the PBA segment
      increases as determined from AFM. For all three templates examined, a maximum in
      porosity (~35% in all cases) and surface area is obtained when the precursor
      solids contain 35-45 wt % PMPEG-PBA. This invariance suggests that the total
      polymer content drives the structure through interfacial assembly. The
      composition for maximizing porosity and surface area with the micelle-templating
      approach results from a general decrease in porosity with increasing cobalt
      nitrate hexahydrate content and the increasing mechanical integrity of the
      framework to resist collapse during template removal/crystallization as the
      cobalt nitrate hexahydrate content increases. Unlike typical evaporation induced
      self-assembly with sol-gel chemistry, the hydrophilic/hydrophobic composition of
      the block copolymer template is not a critical component to the mesostructure
      developed with micelle-templating using metal nitrate-citric acid as the
      precursor.

PMID- 27040317
TI  - Repeated exposures of the male Sprague Dawley rat reproductive tract to
      environmental toxicants: Do earlier exposures to di-(2-ethylhexyl)phthalate
      (DEHP) alter the effects of later exposures?
AB  - Although exposures to environmental toxicants occur throughout life, little
      attention has been paid to the possible effects of exposures early in life on
      later exposure effects. We asked whether DEHP administered in utero (GD14
      parturition) affects how male rats respond to later exposures. Neither in utero
      nor juvenile (PND21-35) exposures to 100mg/kg/day DEHP affected testis weight or
      histology as assessed on PND35. However, after in utero DEHP, subsequent juvenile
      exposure resulted in significantly reduced testis weight and altered testicular
      histology. Both in utero and juvenile exposures resulted in significant
      reductions in serum testosterone, but there was no effect of earlier on later
      exposure. Whether or not there had been in utero DEHP exposure, juvenile DEHP
      exposure had no effect on body, kidney or liver weights. These observations
      indicate that in utero exposure can, but will not necessarily, alter later
      exposure effects, with outcomes dependent upon endpoints measured and dose.

PMID- 27040318
TI  - A study of the neuropsychological correlates in adults with high functioning
      autism spectrum disorders.
AB  - OBJECTIVE: To examine the unique neuropsychological presentation in adults with
      high functioning autism spectrum disorders (HF-ASD) by comparison with adults
      with attention deficit hyperactivity disorder (ADHD). METHODS: Adults with ASD
      referred to a specialty clinic (n=26) were compared to two non-ASD groups with
      (n=52) and without (n=52) ADHD of similar age and sex. RESULTS: No differences in
      IQ were found. Subjects with HF-ASD were significantly more impaired than both
      comparison groups in processing speed, cognitive flexibility and sight words.
      Subjects with HF-ASD were more impaired than controls in working memory, but not
      the ADHD group. CONCLUSION: These findings suggest that there may be specific
      neuropsychological correlates of HF-ASD differing from ADHD that could have
      significant implications for identifying individuals at risk for ASD.

PMID- 27040319
TI  - Disaster Medicine: A Multi-Modality Curriculum Designed and Implemented for
      Emergency Medicine Residents.
AB  - OBJECTIVE: Few established curricula are available for teaching disaster
      medicine. We describe a comprehensive, multi-modality approach focused on
      simulation to teach disaster medicine to emergency medicine residents in a 3-year
      curriculum. METHODS: Residents underwent a 3-year disaster medicine curriculum
      incorporating a variety of venues, personnel, and roles. The curriculum included
      classroom lectures, tabletop exercises, virtual reality simulation, high-fidelity
      simulation, hospital disaster drills, and journal club discussion. All aspects
      were supervised by specialty emergency medicine faculty and followed a structured
      debriefing. Residents rated the high-fidelity simulations by using a 10-point
      Likert scale. RESULTS: Three classes of emergency medicine residents participated
      in the 3-year training program. Residents found the exercise to be realistic,
      educational, and relevant to their practice. After participating in the program,
      residents felt better prepared for future disasters. CONCLUSIONS: Given the large
      scope of impact that disasters potentiate, it is understandably difficult to
      teach these skills effectively. Training programs can utilize this simulation
      based curriculum to better prepare the nation's emergency medicine physicians for
      future disasters. (Disaster Med Public Health Preparedness. 2016;10:611-614).

PMID- 27040320
TI  - A phase 1, open-label, dose-escalation study of pralatrexate in combination with
      bortezomib in patients with relapsed/refractory multiple myeloma.
AB  - Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown
      that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated
      the safety and efficacy of pralatrexate in combination with bortezomib in adults
      with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used.
      Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m(2)
      and intravenous bortezomib at a dose of 1.3 mg/m(2) on days 1, 8 and 15 of each 4
      week cycle. Eleven patients were enrolled and completed a median of two cycles.
      The maximum tolerated dose was 20 mg/m(2) . Two patients experienced dose
      limiting toxicity of mucositis. The most frequent non-haematological toxicities
      were fatigue (55%) and mucositis (45%). There were three serious adverse events
      in three patients: rash, sepsis and hypotension. One patient (9%) had a very good
      partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and
      two (18%) had progressive disease. The median duration of response was 4 months,
      the median time to next treatment was 3.4 months and the median time to
      progression was 4 months. Pralatrexate, in combination with bortezomib, was
      generally safe and demonstrated modest activity in relapsed or refractory
      multiple myeloma. Clinicaltrials.gov identifier: NCT01114282. 

PMID- 27040321
TI  - Prognostic significance of DSG3 in rectal adenocarcinoma treated with
      preoperative chemoradiotherapy.
AB  - AIM: This study aimed to investigate the prognostic significance of DSG3 and its
      association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in
      rectal cancer. MATERIALS & METHODS: Data mining of a publicly available dataset
      was performed to find genes associated with CCRT response. Immunohistochemistry
      was applied to evaluate DSG3 expression. The relationships between DSG3
      expression and various clinicopathological parameters and survival were analyzed.
      RESULTS: The DSG3 gene was significantly associated with CCRT response. The
      expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001)
      and had an independent negative impact on disease-specific survival (p = 0.011),
      local recurrence-free survival (p = 0.031) and metastasis-free survival (p =
      0.029). CONCLUSION: DSG3 was a key prognostic factor and predictor for CCRT
      response in rectal cancer patients.

PMID- 27040322
TI  - Phenotype and genotype comparisons in carriers of haemophilia A.

PMID- 27040323
TI  - Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low
      birth weight neonates.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common emergency
      involving the gastrointestinal tract occurring in the neonatal period. There have
      been published reports that suggest that oral immunoglobulins (Ig)A and IgG
      produce an immunoprotective effect in the gastrointestinal mucosa. OBJECTIVES: To
      determine the effect of oral immunoglobulin on the incidence of necrotizing
      enterocolitis and other complications in preterm or low birth weight (or both)
      neonates. SEARCH METHODS: We used the standard search strategy of the Cochrane
      Neonatal Group. We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library 2016, Issue 1), PubMed (1966 to January 2016),
      CINAHL (1982 to January 2016) and EMBASE (1980 to January 2016) and conference
      proceedings. SELECTION CRITERIA: All randomized or quasi-randomised controlled
      trials where oral immunoglobulins were used as prophylaxis against NEC in preterm
      (less than 37 weeks' gestation) or low birth weight (less than 2500 gram), or
      both, neonates. DATA COLLECTION AND ANALYSIS: We performed data collection and
      analysis in accordance with the standard methods of the Cochrane Neonatal Review
      Group. MAIN RESULTS: The search identified five studies on oral immunoglobulin
      for the prevention of NEC of which three met the inclusion criteria. In this
      review of the three eligible trials (including 2095 neonates), the oral
      administration of IgG or an IgG/IgA combination did not result in a significant
      reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95%
      confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI
      -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to
      1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery
      (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2
      studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59;
      typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants). AUTHORS'
      CONCLUSIONS: Based on the available trials, the evidence does not support the
      administration of oral immunoglobulin for the prevention of NEC. There are no
      randomized controlled trials of oral IgA alone for the prevention of NEC.

PMID- 27040325
TI  - Development of Unlabeled Probe Based High-Resolution Melting Analysis for
      Detection of Filaggrin Gene Mutation c.3321delA.
AB  - BACKGROUND: Filaggrin gene (FLG) plays an important role in skin barrier
      function, and loss-of-function mutations of FLG have been shown to be a
      predisposing factor for atopic dermatitis (AD). The c.3321delA mutation is the
      most common FLG mutation in Chinese population. We aim to develop a rapid, cost
      efficiency, and reliable closed-tube method that has not been described for the
      detection of c.3321delA mutation. METHODS: Recombinant wild-type and mutant
      plasmids of c.3321delA mutation were constructed, heterozygous mutant plasmids
      were prepared by mixing the mutant plasmids and wild-type plasmids at 1:1 ratio.
      High-resolution melting analysis (HRMA) coupled with an unlabeled DNA probe was
      employed to identify the shift in melting temperature of the probe-template
      complex, which reflects the presence of c.3321delA mutation. RESULTS: Unlabeled
      probe based HRMA was able to distinguish all three genotypes (wild-type,
      heterozygote, and mutant) of c.3321delA mutation. Then, we applied this method to
      genotype 1,317 clinical samples. Genotyping results obtained from unlabeled probe
      HRMA were 100% concordant with the results from direct sequencing. CONCLUSION: We
      developed a fast and high-throughput method to detect the c.3321delA mutation.

PMID- 27040326
TI  - One-step electrochemical synthesis of nitrogen and sulfur co-doped, high-quality
      graphene oxide.
AB  - High-quality graphene oxide (GO) with high crystallinity and electrical
      conductivity as well as in situ doped with nitrogen and sulfur is obtained via
      the electrochemical exfoliation of graphite. Furthermore, iron incorporated GO
      sheets show promising catalytic activity and stable methanol tolerance durability
      when used as electrocatalysts for the oxygen reduction reaction. 

PMID- 27040327
TI  - The increasing of pedicled propeller perforator flap survival by an extra vein
      anastomosis.

PMID- 27040329
TI  - Fatal transfusion-transmitted infection due to Citrobacter koseri.
AB  - BACKGROUND: Transfusion-transmitted bacterial infection (TTBI) is still one of
      the most feared complications of blood transfusion. CASE REPORT: We report a
      fatal case involving an 8-year-old child with congenital dyskeratosis complicated
      by severe aplastic anemia who was regularly transfused with platelet (PLT)
      concentrates for 5 years. The patient received an apheresis PLT concentrate (APC)
      on Day 0 due to thrombocytopenia complicated by mucocutaneous hemorrhage. Thirty
      minutes after the start of the transfusion, bradycardia and dyspnea appeared,
      quickly followed by chills, nausea, vomiting, headache, and hyperthermia. TTBI
      was suspected and the patient was immediately treated with intravascular
      antibiotherapy. On Day 3, the patient developed severe acute respiratory distress
      syndrome leading to death on Day 7. Patient blood cultures and APC cultures were
      both positive for Citrobacter koseri. RESULTS: The donor was a 19-year-old woman.
      She had previously given blood. No infectious symptom was reported during the
      medical interviews before and after the donation and no postdonation information
      was received. On the day of the donation (Day -2), her white blood cell count was
      5.83 * 109 /L. She came back on Day 8 to undergo additional tests. The cultures
      from blood, stool, urine, the skin of the inside of the elbow at the point of
      needle insertion, and ear samples were all negative for C. koseri. However, a
      nasal sample was positive for C. koseri. CONCLUSION: The isolates from the
      donor's blood cultures, the APC bag, the attached tube, and the donor's nasal
      sample all gave identical profiles; they were thus identified as the same strain
      and the TTBI was confirmed.

PMID- 27040330
TI  - The fat-but-fit paradigm and all-cause mortality among coronary artery disease
      patients.
AB  - BACKGROUND: Limited research has examined the fat-but-fit paradigm among coronary
      artery disease patients. OBJECTIVES: The objective of this study was to evaluate
      the fat-but-fit paradigm as it relates to mortality risk among patients with
      coronary artery disease. METHODS: A total of 766 coronary artery disease patients
      (Mage = 65.4 years) were evaluated. Physical activity was assessed via self
      report, with weight status determined from measured body mass index. Six mutually
      exclusive groups were evaluated, including (i) Normal Weight and Inactive
      (referent), (ii) Overweight and Inactive, (iii) Obese and Inactive, (iv) Normal
      Weight and Active, (v) Overweight and Active and (vi) Obese and Active. RESULTS:
      A total of 301 died over the follow-up period, with the duration of the
      unweighted median follow-up period being 86 months (IQR: 62-113). The Cox
      proportional hazard results, after adjusting for age, gender, and race-ethnicity,
      were as follows: Group 2: HRadjusted = 0.95, 95% CI: 0.57-1.60, p = 0.87; Group
      3: HRadjusted = 0.91, 95% CI: 0.57-1.44, p = 0.68; Group 4: HRadjusted = 0.35,
      95% CI: 0.14-0.86, p = 0.02; Group 5: HRadjusted = 0.51, 95% CI: 0.28-0.93, p =
      0.02; Group 6: HRadjusted = 0.43, 95% CI: 0.21-0.85, p = 0.01. CONCLUSION: These
      findings provide support for the fat-but-fit paradigm applied to CAD patients.
      Ultimately, these findings underscore the importance of promoting physical
      activity to all weight groups of CAD patients.

PMID- 27040328
TI  - CD300c is uniquely expressed on CD56 bright Natural Killer Cells and differs from
      CD300a upon ligand recognition.
AB  - Paired receptors on NK cells recognize similar ligands with varied strength of
      binding ability and perform different functions. The CD300 molecules are emerging
      as novel immune regulators in health and disease due to their interaction with
      their lipid-nature ligands. Particularly, the paired receptors CD300c and CD300a
      have been shown to elicit activating and inhibitory capabilities, respectively.
      In the current study, we seek to investigate the expression and function of
      CD300c on human NK cells. We demonstrate that IL-2 and IL-15 treatment
      significantly induce CD300c expression exclusively on CD56(bright) NK cells.
      CD300c up-regulation requires STAT5 and its expression is inhibited by IL-4.
      Consistently, IL-2 secreted from activated CD4(+) T cells specifically induces
      the expression of CD300c on CD56(bright) NK cells. Crosslinking CD300c with a
      specific antibody enhances the proficiency of CD56(bright) NK cells to
      degranulate and induce chemokine and cytokine secretion. We also show the
      differential binding of CD300a and CD300c to their ligands
      phosphatidylethanolamine (PE) and phosphatidylserine (PS) and their differential
      ability to affect CD56(bright) NK cell functions. Our results provide an insight
      into the novel set of paired receptors CD300a and CD300c that are distinctively
      expressed on CD56(bright) NK cells with varied effector functions.

PMID- 27040331
TI  - Secondary Bruch's membrane defects and scleral staphyloma in toxoplasmosis.

PMID- 27040332
TI  - [Future Vision of Regulatory Science in the Global Development of Pharmaceuticals
      and Medical Devices].

PMID- 27040333
TI  - [New Medical Device Evaluation].
AB  - In this presentation, as a member of the Harmonization by Doing (HBD) project, I
      discuss the significance of regulatory science in global medical device
      development and our experience in the international collaboration process for
      medical devices. In Japan, most innovative medical therapeutic devices were
      previously developed and exported by foreign-based companies. Due to this device
      lag, Japanese had minimal opportunities for receiving treatment with innovative
      medical devices. To address this issue, the Japanese government has actively
      accepted foreign clinical trial results and promoted global clinical trials in
      projects such as HBD. HBD is a project with stakeholders from academia,
      regulatory authorities, and industry in the US and Japan to promote global
      clinical trials and reduce device lags. When the project started, medical device
      clinical trials were not actively conducted in Japan at not just hospitals but
      also at medical device companies. We started to identify issues under the concept
      of HBD. After 10 years, we have now become key members in global clinical trials
      and able to obtain approvals without delay. Recently, HBD has started promoting
      international convergence. Physicians and regulatory authorities play central
      roles in compiling guidelines for the clinical evaluation of medical device
      development, which will be a more active field in the near future. The guidelines
      compiled will be confirmed with members of academia and regulatory authorities in
      the United Sates. 

PMID- 27040334
TI  - [Future Regulatory Science through a Global Product Development Strategy to
      Overcome the Device Lag].
AB  - Environment that created "medical device lag (MDL)" has changed dramatically, and
      currently that term is not heard often. This was mainly achieved through the
      leadership of three groups: government, which determined to overcome MDL and took
      steps to do so; medical societies, which exhibited accountability in trial
      participation; and MD companies, which underwent a change in mindset that allowed
      comprehensive tripartite cooperation to reach the current stage. In particular,
      the global product development strategy (GPDS) of companies in a changing social
      environment has taken a new-turn with international harmonization trends, like
      Global Harmonization Task Force and International Council for Harmonisation of
      Technical Requirements for Registration of Pharmaceuticals for Human Use. As a
      result, this evolution has created opportunities for treatment with cutting-edge
      MDs in Japanese society. Simultaneously, it has had a major impact on the
      planning process of GPDS of companies. At the same time, the interest of global
      companies has shifted to emerging economies for future potential profit since
      Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem
      for manufacturers. From the regulatory science viewpoint, this new environment
      has not made it easy to plan a global strategy that will be adaptable to local
      societies. Without taking hasty action, flexible thinking from the global point
      of view is necessary to enable the adjustment of local strategies to fit the
      situation on the ground so that the innovative Japanese medical technology can be
      exported to a broad range of societies. 

PMID- 27040335
TI  - [Quantitative Decision Making in Drug Development: Pharmacometrics].
AB  - According to the US Food and Drug Administration, pharmacometrics is an emerging
      science that quantifies drugs, diseases, and trial information to aid efficient
      drug development and/or regulatory decisions. Quantitative decision making occurs
      at all stages of drug development. In general, patient-level data are not made
      available to competitors. However, summary-level data are available. Model-based
      meta-analysis (MBMA) is a powerful tool for decision making which identifies the
      candidate position in the market. The limitation of MBMA is the heterogeneity of
      the treatment effect. In the near future, MBMA application is expected at every
      stage of drug development. 

PMID- 27040324
TI  - Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.
AB  - BACKGROUND: Previous trials have shown that among high-risk patients with aortic
      stenosis, survival rates are similar with transcatheter aortic-valve replacement
      (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in
      a randomized trial involving intermediate-risk patients. METHODS: We randomly
      assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57
      centers, to undergo either TAVR or surgical replacement. The primary end point
      was death from any cause or disabling stroke at 2 years. The primary hypothesis
      was that TAVR would not be inferior to surgical replacement. Before
      randomization, patients were entered into one of two cohorts on the basis of
      clinical and imaging findings; 76.3% of the patients were included in the
      transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS:
      The rate of death from any cause or disabling stroke was similar in the TAVR
      group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan
      Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group
      (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to
      1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate
      of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to
      1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar
      in the two groups. TAVR resulted in larger aortic-valve areas than did surgery
      and also resulted in lower rates of acute kidney injury, severe bleeding, and new
      onset atrial fibrillation; surgery resulted in fewer major vascular complications
      and less paravalvular aortic regurgitation. CONCLUSIONS: In intermediate-risk
      patients, TAVR was similar to surgical aortic-valve replacement with respect to
      the primary end point of death or disabling stroke. (Funded by Edwards
      Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

PMID- 27040336
TI  - [Role of Academia in Regulatory Science for Global Drug Development].
AB  - As diseases know no national boundaries, drug development must be designed at a
      global level. Drugs are highly regulated to maximize the benefits to public
      health, which is assessed on a regional basis. The complexity and diversity of
      stakeholders increase dramatically once multiple international regions are
      involved. Each stakeholder in drug development depends on customized criteria to
      make decisions for its own benefit. Thus, a huge gap exists among drug discovery
      researchers, developers, clinicians, patients, and regulatory bodies. With
      reasonable scientific evidence gathered and analyzed, mutual agreement can be
      reached. We believe that this important role of regulatory science and academic
      involvement will create harmony. By practicing diverse, innovative regulatory
      scientific research, academia has the potential to become the core of
      communication among various stakeholder groups. Furthermore, another important
      responsibility of academia, i.e., knowledge, provides additional aspects to the
      field of drug development. Those who understand regulatory science can contribute
      to the efficient achievement of innovative, effective, safe drugs. Thus, research
      and education are essential roles of academia to allow a better understanding of
      the balance between benefits and risks. Communication and knowledge will promote
      the prompt delivery of better medical products to patients in need. 

PMID- 27040337
TI  - [Analysis of Spontaneously Reported Adverse Events].
AB  - Observational study is necessary for the evaluation of drug effectiveness in
      clinical practice. In recent years, the use of spontaneous reporting systems
      (SRS) for adverse drug reactions has increased and they have become an important
      resource for regulatory science. SRS, being the largest and most well-known
      databases worldwide, are one of the primary tools used for postmarketing
      surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug
      Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse
      Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance
      algorithms were used for signal detection, including the reporting odds ratio. An
      SRS is a passive reporting database and is therefore subject to numerous sources
      of selection bias, including overreporting, underreporting, and a lack of a
      denominator. Despite the inherent limitations of spontaneous reporting, SRS
      databases are a rich resource and data mining index that provide powerful means
      of identifying potential associations between drugs and their adverse effects.
      Our results, which are based on the evaluation of SRS databases, provide
      essential knowledge that could improve our understanding of clinical issues. 

PMID- 27040338
TI  - [Regulatory Science in the Review of Drugs and Medical Devices].
AB  - The review of drugs and medical devices is an integral part of regulatory
      science. The Pharmaceuticals and Medical Devices Agency (PMDA) evaluates the
      efficacy, safety, and quality of drugs and medical devices after applications are
      submitted for regulatory approval. The products are approved when their benefits
      exceed their risks, i.e., an application is approved if the efficacy of the
      product in patients was demonstrated and the safety of the product is acceptable
      in view of its observed benefits. However, drugs and medical devices for which
      efficacy was not clearly demonstrated in clinical trials makes the decision to
      approve a difficult process. Under those circumstances, the approval process is
      based on the totality of information, such as the reason why clinical trials did
      not succeed and medical needs in Japan. The Wingspan stent system, which was
      approved for the treatment of intracranial arterial stenosis, is an example of a
      product with a use different from that intended by the US Food and Drug
      Administration and PMDA. 

PMID- 27040339
TI  - [Current Status and Future Prospects of Nonalcoholic Fatty Liver Disease (NAFLD)
      in Japan-Feedback from Clinical and Basic Researches to Medical Therapy and
      Pharmacist Activities].

PMID- 27040340
TI  - [An Overview of NAFLD/NASH in Japan].
AB  - Clinical identity of nonalcoholic steatohepatitis (NASH) has established it as a
      chronic liver disease since the 1990s in the USA and in the 21st century in
      Japan, although its significance is not well recognized in Japanese society. It
      is characterized as a chronic liver disease, differentiated from viral liver
      disease and alcoholic liver disease. Nonalcoholic fatty liver disease (NAFLD)
      comprises nonalcoholic fatty liver (NAFL) and NASH. NASH is considered to be the
      hepatic manifestation of a metabolic syndrome. It is understood that among
      individuals with NAFLD, NAFL is a benign condition, whereas NASH can progress to
      cirrhosis and ultimately to hepatocellular carcinoma. The precise mechanism of
      NASH is poorly understood, although insulin resistance, oxidative stress and
      multiple parallel hits theory have been reported. Computed tomography and
      ultrasonography are performed to detect NAFLD, but these are not sufficient to
      distinguish between NAFL and NASH. The distinct diagnosis of NAFL and NASH is
      currently made by liver biopsy, requiring hospitalization. Therefore, there is an
      urgent need to develop simple, non-invasive markers that can accurately
      distinguish between NASH and NAFL. In Japan, the number of NASH patients is
      estimated to be about 1 million. The treatment of NASH comprises changes in life
      style, including eating habits and exercise that will lead to weight loss, and
      drug intake, including vitamin E. Based on the global increase in obese people,
      NASH as a chronic liver disease will become the most important chronic liver
      disease in the 21st century, not only in Japan but also worldwide. 

PMID- 27040341
TI  - [Incretin as a Novel Treatment Strategy for NAFLD/NASH].
AB  - Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
      have been recognized as metabolic disorders characterized by fatty accumulation
      in the liver without alcohol consumption. The diseases can cause metabolic
      syndromes, consisting of obesity, diabetes mellitus (DM), dyslipidemia and
      hypertension. For the treatment of NAFLD/NASH, losing weight by exercise or diet
      remains the standard treatment, because no effective pharmacological therapy has
      yet been developed for NAFLD/NASH. Two incretin hormones, glucagon-like peptide-1
      (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), stimulate glucose
      mediated insulin production in pancreatic beta cells. Incretin has also been
      reported to have various extra-pancreatic effects, including the regulation of
      hepatic glucose production, appetite and satiety, as well as the stimulation of
      afferent sensory nerves. Therefore, incretin may have potential as a novel
      therapeutic agent for NAFLD/NASH. 

PMID- 27040342
TI  - [Drug-induced Nonalcoholic Steatohepatitis].
AB  - Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease
      characterized by intense liver steatosis accompanied by hepatocyte destruction,
      inflammation and fibrous, despite little or no history of alcoholic consumption.
      There are also cases of drug-induced secondary steatohepatitis. Drug-induced
      steatohepatitis is a relatively rare type of drug-induced liver disease, but
      close attention to the possible onset of steatohepatitis is needed when drugs
      with the potential to induce fatty liver are prescribed for long term use.
      Estrogen is a factor indispensable to smooth fatty acid beta-oxidation in
      hepatocytes. However, treatment with Tamoxifen markedly suppresses fatty acid
      beta-oxidation in the liver. As free fatty acids are toxic, their accumulation
      results in the activation of alternative fatty acid oxidation pathways mediated
      by CYP2E1 in cytosol and lipid peroxidases in peroxisomes in hepatocytes. CYP2E1
      enhances lipid peroxidation and dicarboxylic acid synthesis via the activation of
      fatty acid omega-oxidation that injures mitochondria and results in the emergence
      of ballooned hepatocytes. In such cases, the attenuation of alternative fatty
      acid oxidation pathways could have some beneficial effects on mitochondrial
      injury, since fibrates (PPAR-alpha ligands) are potent enough to stimulate
      neutral fat consumption through the activation of peroxisomal fatty acid beta
      oxidation. Fortunately, fibrates attenuate serum estrogen levels by affecting
      estrogen receptor expression, so the co-administration of fibrates with Tamoxifen
      is expected to exert higher efficacy in breast cancer patients with Tamoxifen
      induced hepatic steatosis. 

PMID- 27040343
TI  - [A Future Perspective on the Involvement of n-3 Polyunsaturated Fatty Acid in the
      Development of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis].
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by the pathological
      accumulation of fat in the liver in the absence of any other disease related to
      liver steatosis, which includes a wide spectrum of liver diseases ranging from
      mild asymptomatic fatty liver to nonalcoholic steatohepatitis (NASH) and
      cirrhosis. Recently, it was reported that NAFLD is characterized by the impaired
      bioavailability of liver n-6 and n-3 long-chain polyunsaturated fatty acids
      (PUFAs). That is, compared with healthy individuals, steatosis and
      steatohepatitis patients have higher n-6/n-3 PUFA ratios. Furthermore, per recent
      research, decreasing the intake of total fats and increasing the intake of n-3
      PUFAs may be beneficial in the treatment of NAFLD. In contrast, some reports
      describe that NASH patients have more metabolic abnormalities than NAFLD
      patients; however, these are not influenced by dietary fatty acids. Thus, at
      present, various opinions exist regarding the efficacy of n-3 PUFA in the
      treatment of NAFLD. In this review, we discuss the considerable interest n-3 PUFA
      has attracted as a potential treatment for NAFLD. 

PMID- 27040344
TI  - [Characteristics and Functional Roles of Opioids Originally Present in Vivo].
AB  - The characteristics and functional roles of opioids originally present in vivo
      (endogenous opioids) in guinea-pig ileum were investigated. The release of
      endogenous opioids was determined by the inhibitory twitch response evoked by 0.1
      Hz stimulation after 10 Hz stimulation (post-tetanic twitch inhibition). The
      effects of peptidase inhibitors increased the post-tetanic twitch inhibition,
      prevented by beta-funaltrexamine and nor-binaltorphimine, which are selective MU-
      and kappa-opioid receptor subtype antagonists, respectively. Dopamine receptor
      antagonists (haloperidol, sultopride and domperidone) increased the post-tetanic
      twitch inhibition. These results suggest that dopamine receptors are involved in
      modulation of the ileal opioid system, so as to diminish endogenous opioid
      release by tetanic stimulation, and dopamine antagonists increase the opioid
      action, that might depend more on the increased release of endogenous opioids.
      The post-tetanic twitch inhibition was inhibited by adrenalectomy, and showed the
      supersensitivity of the opioid receptors, resulting from a decrease of endogenous
      opioids by adrenalectomy. These findings suggest that the increase in morphine
      analgesia by adrenalectomy was due to this process. In the presence of naloxone,
      an opioid antagonist, an increase in basal tension after tetanic stimulation (10
      Hz stimulation) (post-tetanic contraction) was observed, and was blocked by
      spantide, a substance P antagonist, and indomethacin, a prostaglandins
      biosynthesis inhibitor. This contraction increased with morphine or peptidase
      inhibitor exposure, depending on the length of time the ileum was exposed to the
      morphine or peptidase inhibitor. Post-tetanic contraction might be a useful
      indicator of the formation of physical dependence to morphine or endogenous
      opioids in the ileum. 

PMID- 27040345
TI  - [Synthetic Studies of Bioactive Heterocyclic Natural Products and Fused
      Heterocyclic Compounds Based on the Thermal Electrocyclic or Azaelectocyclic
      Reaction of 6pi-Electron or Aza-6pi-electron Systems].
AB  - Since 1979, synthetic studies of bioactive heterocyclic natural products and
      condensed heteroaromatic compounds based on the thermal electrocyclic reaction of
      6pi-electron or aza-6pi-electron systems incorporating the double bond of the
      principal aromatic or heteroaromatic ring have been conducted by our research
      group. In this review, five types of electrocyclic and azaelectrocyclic reaction
      are described: 1) the synthesis of the carbazole alkaloids hyellazole and 6
      chlorohyellazole through the electrocyclic reaction of 2,3-bisalkenylindoles; 2)
      synthetic studies of the pyridocarbazole alkaloids ellipticine and olivacine
      through the electrocyclic reactions of the indole-2,3- and pyridine-3,4
      quinodimethane intermediates; 3) synthetic studies of polysubstituted carbazole
      alkaloids through the allene-mediated electrocyclic reactions involving the
      indole 2,3-bond; 4) synthetic studies of fused pyridine rings through the
      azaelectrocyclic reaction of the 1-aza-6pi-electron system using the oxime or
      oxime ether; and 5) synthetic studies of fused pyridine rings through the
      azaelectrocyclic reaction of the 2-aza-6pi-electron system using a carbodiimide
      or isocyanate. 

PMID- 27040346
TI  - [Molecular Mechanisms of Early-stage Adipocyte Differentiation and Multi
      functional Roles of Newly Isolated Adipogenic Factors].
AB  - Obesity is a major risk factor for diabetes, hypertension, hyperlipidemia, and
      arteriosclerosis. Although the middle and late stages of adipocyte
      differentiation are well characterized, the earliest step in the differentiation
      process has remained largely unknown. We isolated 102 genes expressed at the
      beginning of the differentiation of a mouse preadipocyte cell line, 3T3-L1 cells.
      Because approximately half of these genes were unknown, we named them factor for
      adipocyte differentiation (fad) genes. I first show how these genes regulate the
      early stage of adipocyte differentiation. We next generated fad104-deficient
      mice, and demonstrated that fad104-deficient mice died due to cyanosis-associated
      lung dysplasia with atelectasis. We also found that fad104 positively regulated
      adipocyte differentiation and negatively regulated osteoblast differentiation. We
      then demonstrated that fad24-knockdown inhibited mitotic clonal expansion (MCE)
      and that FAD24 contributed to the regulation of DNA replication by recruiting
      histone acetyltransferase binding to ORC1 (HBO1) to DNA replication origins. In
      vitro culture experiments revealed that fad24-null embryos developed normally to
      the morula stage, but acquired growth defects in subsequent stages. These results
      strongly suggest that fad24 is essential for pre-implantation in embryonic
      development, particularly for progression to the blastocyst stage. These findings
      together indicate that both fad104 and fad24 contribute not only to adipogenesis
      but also to other physiological events. The multi-functional roles of these genes
      are discussed. 

PMID- 27040347
TI  - [Development of Radiolabeled Molecular Imaging Probes for in Vivo Analysis of
      Biological Function].
AB  - Molecular imaging is a newly emerging field aimed at advancing our understanding
      of biology and medicine through the noninvasive in vivo investigation of cellular
      molecular events involved in normal and pathologic processes. In this field,
      researchers and/or clinicians are combining modern tools of molecular and cell
      biology with state of the art technology in order to noninvasively image living
      subjects. Various imaging modalities such as optics (fluorescence and
      luminescence), nuclear magnetic resonance imaging, ultrasound, and radiation are
      being used to visually capture and study molecular and cellular events in living
      organisms. Among these modalities, nuclear medical molecular imaging uses
      radionuclides [i.e., positron emission tomography (PET) and single-photon
      emission computed tomography (SPECT)], and has characteristic properties that
      allow researchers and/or clinicians to obtain functional images of living
      subjects with high sensitivity. Translational molecular imaging, a research step
      between animal experiments and the clinical setting, has been successful when
      using nuclear medical molecular imaging. This approach leads to better methods
      for studying biological processes, as well as for diagnosing and managing
      diseases. In this review, two topics associated with our research on nuclear
      medical molecular imaging are summarized: (1) the development of a nuclear
      medical molecular imaging probe that targets cerebral nicotinic acetylcholine
      receptors (nAChRs), and the translational molecular imaging research conducted
      using this nAChR imaging probe; and (2) the development of oxygen-dependent
      degradable nuclear medical molecular imaging probes that target hypoxia-inducible
      factor-1-active tumor microenvironments. 

PMID- 27040348
TI  - [Exploring New Drug Targets through the Identification of Target Molecules of
      Bioactive Natural Products].
AB  - With the development of cell biology and microbiology, it has become easy to
      culture many types of animal cells and microbes, and they are frequently used for
      phenotypic screening to explore medicinal seeds. On the other hand, it is
      recognized that cells and pathogenic microbes present in pathologic sites and
      infected regions of the human body display unique properties different from those
      under general culture conditions. We isolated several bioactive compounds from
      marine medicinal resources using constructed bioassay-guided separation focusing
      on the unique changes in the characteristics of cells and pathogenic microbes
      (Mycobacterium spp.) in the human body under disease conditions. In addition, we
      also carried out identification studies of target molecules of the bioactive
      compounds by methods utilizing the gene expression profile, transformants of
      cells or microbes, synthetic probe molecules of the isolated compounds, etc.,
      since bioactive compounds isolated from the phenotypic screening system often
      target new molecules. This review presents our phenotypic screening systems,
      isolation of bioactive compounds from marine medicinal resources, and target
      identification of bioactive compounds. 

PMID- 27040349
TI  - [Evaluation of Gastric Mucosal Injury Model Animals of Rebamipide Formulation-
      Study of Therapeutic Equivalence].
AB  - The introduction of generic drugs is promoted from the perspective of medical
      economics. In this context, we need to understand not only the bioequivalence of
      generic drugs specified in "the Guidelines for Bioequivalence Studies of Generic
      Products", but also formulation properties to consider their effect on
      pharmacological therapy. We evaluated the pharmaceutical characteristics of
      rebamipide formulations, a brand-name drug and two generic drugs, and their
      clinical functionality by using rat models of gastric mucosal injury induced by
      non-steroidal anti-inflammatory drugs (NSAIDs). Pharmaceutical evaluation showed
      significant differences in hardness. The inter-lot variation was small in all
      rebamipide formulations. In the clinical functionality study, biochemistry test
      values 7 d after the administration of rebamipide showed no differences among
      formulations. Higher levels of mucosal fluid secretion and antioxidative enzymes
      were observed in the groups administered rebamipide than in the control group.
      The levels of lipid peroxide were lower in the groups administered rebamipide
      than the control group. Multivariate analysis showed slight divergence between
      the brand-name and generic drugs. In future, it will be necessary to select
      generic drugs after careful consideration of bioequivalence, clinical
      functionality, and therapeutic equivalence by reviewing scientific evidence such
      as indication and formulation design, not to mention stable provision. 

PMID- 27040350
TI  - Changes in milk composition associated with pethidine-PCEA usage after Caesarean
      section.
AB  - The effect of pethidine as patient-controlled epidural analgesia (PCEA) on
      specific biochemical components in breast milk in relation to the timing of
      secretory activation is not well investigated. The aim of this study was to
      compare biochemical timing of secretory activation between women who had a
      vaginal (V) or Caesarean birth with pethidine-PCEA (CBP). Several milk samples
      were collected daily from 36 mothers (17 V, 19 CBP) for the first 265 h post
      partum. Protein and lactose concentrations and Na+ and K+ ion levels were
      measured. Samples were assigned to three time periods: 0-72, >72-165 and >165-265
      h post-partum for statistical analyses. Data were analyzed using linear mixed
      effect models. In the first 72 h post-partum, the mean difference in lactose
      concentration was 5 gL-1 higher in group V (P < 0.05). From >72-165 h post
      partum, protein and Na+ concentrations were lower in group V (P = 0.05, P =
      0.02), and K+ levels were higher in group V (P < 0.001). From >165-265 h post
      partum, there were no significant differences between the groups. Biochemically,
      secretory activation had occurred by 72 h post-partum in both groups. There were
      greater variations in measured biochemical components observed within group CBP
      initially. However, by 165 h post-partum, there were no differences in the
      biochemical components between the groups. This suggests that effects of
      pethidine-PCEA are diminished by 72 h post-partum and undetected by 165 h.

PMID- 27040351
TI  - Tropical Skin Diseases in Children: A Review- Part I.
AB  - Because of travel and migration patterns, tropical skin diseases are now seen all
      around the world, not just in tropical or developing countries. Nutrition,
      housing, and environmental factors play an important role in these infectious
      diseases, so when they appear out of their normal environments, their classic
      presentation may vary. Tropical diseases can also present differently in
      childhood, making their recognition, diagnosis, and management a clinical
      challenge. Health care providers in developed countries need to be familiar with
      tropical skin diseases and be able to diagnose them in returning travelers or
      immigrants in order to optimize care. This article aims to review the
      epidemiologic, clinical, diagnostic, and therapeutic aspects of some of the most
      common tropical dermatologic conditions in children. 

PMID- 27040352
TI  - Blue honeysuckle fruit (Lonicera caerulea L.) from eastern Russia: phenolic
      composition, nutritional value and biological activities of its polar extracts.
AB  - In the present work we conducted a comprehensive chemical analysis of blue
      honeysuckle (Lonicera caerulea) spontaneously growing in eastern Russia. HPLC-DAD
      ESI/MS analysis showed cyanidin-3-glucoside as the major constituent among
      phenolics, while nutritional analysis revealed fibre, protein, calcium and
      magnesium as the most important macro- and micronutrients, respectively. Fatty
      acid composition was dominated by polyunsaturated fatty acids, linoleic acid
      being the most abundant. Furthermore, we evaluated several in vitro biological
      activities such as antioxidant, antimicrobial, antiproliferative, wound healing
      and immunomodulatory effects of blue honeysuckle aqueous and ethanolic extracts
      that are often incorporated in food and nutraceutical preparations. While the
      fruit extracts were revealed to be potent radical scavengers with significant
      inhibition of ABTS radical, thus confirming the literature data, their inhibitory
      effects against microbial pathogens and tumor cell lines were negligible. The
      fruit aqueous extract did not show toxicity to human fibroblasts, but 24 h
      treatment with 150-200 MUg per mL of extract slightly enhanced the cell migration
      when tested by scratched wound assay. Worth mentioning was the inhibitory effect
      displayed by the blue honeysuckle fruit aqueous extract on human lymphocytes. 

PMID- 27040353
TI  - Mechanisms and Therapeutic Targets of microRNA-associated Chemoresistance in
      Epithelial Ovarian Cancer.
AB  - Epithelial ovarian cancer (EOC) is the most lethal disease among gynecologic
      malignancies. Despite increasing knowledge of ovarian cancer biology and advances
      in treatment efficacy, the survival rate of patients with EOC has not improved
      over the past two decades. Patients with an advanced disease often relapse due to
      the development of chemoresistance. Recent in vivo and in vitro studies have
      shown insight into the mechanisms of such drug resistance, including a potential
      role for microRNAs (miRNA, miR) in the process of chemoresistance. In this
      review, we provide an overview of current therapeutic targets of miRNA-associated
      chemoresistance in EOC and discuss potential therapeutic values and molecular
      mechanisms by which miRNAs influence the development and reversal of
      chemoresistance.

PMID- 27040354
TI  - Early stages of catalyst aging in the iridium mediated water oxidation reaction.
AB  - When exposed to a potential exceeding 1.5 V versus RHE for several minutes the
      molecular iridium bishydroxide complex bearing a pentamethylcyclopentadienyl and
      a N-dimethylimidazolin-2-ylidene ligand spontaneously adsorbs onto the surface of
      glassy carbon and gold electrodes. Simultaneously with the adsorption of the
      material on the electrode, the evolution of dioxygen is detected and
      modifications of the catalyst structure are observed. XPS and XAS studies reveal
      that the species present at the electrode interface is best described as a partly
      oxidized molecular species rather than the formation of large aggregates of
      iridium oxide. These findings are in line with the unique kinetic profile of the
      parent complex in the water oxidation reaction. 

PMID- 27040355
TI  - Relationship Between Blood Pressure Values, Depressive Symptoms, and
      Cardiovascular Outcomes in Patients With Cardiometabolic Disease.
AB  - The authors studied the joint effect of blood pressure (BP) and depression on the
      risk of major adverse cardiovascular outcome in patients with existing
      cardiometabolic disease. A cohort of 35,537 patients with coronary heart disease,
      diabetes, or stroke underwent depression screening and BP measurement recorded
      concurrently. The authors used Cox's proportional hazards to calculate risk of
      major adverse cardiovascular event (MACE; myocardial infarction/heart
      failure/stroke or cardiovascular death) over 4 years associated with baseline BP
      and depression. A total of 11% (3939) had experienced a MACE within 4 years.
      Patients with very high systolic BP (160-240 mm Hg; hazard ratio, 1.28) and
      depression (hazard ratio, 1.22) at baseline had significantly higher adjusted
      risk. Depression had a significant interaction with systolic BP in risk
      prediction (P=.03). Patients with a combination of high systolic BP and
      depression at baseline had 83% higher adjusted risk of MACE, as compared with
      patients with reference systolic BP without depression. Patients with
      cardiometabolic disease and comorbid depression may benefit from closer
      monitoring of systolic BP.

PMID- 27040356
TI  - Asymmetric hearing loss is common and benign in patients aged 95 years and older.
AB  - OBJECTIVES/HYPOTHESIS: The objective of our study was to investigate age-specific
      auditory function in the patient population aged 95 years and older. STUDY
      DESIGN: Retrospective chart review at a tertiary medical center. METHODS: Medical
      records of 51 patients older than 95 years (82% female, 18% male) who underwent
      audiologic testing were reviewed. The following information was collected: age at
      time of most recent audiogram and prior audiograms; results of pure tone,
      immittance, and speech audiometry; and findings on radiologic imaging. RESULTS:
      None of the subjects had hearing in the normal range. For the poorer hearing ear,
      average low-frequency, high-frequency, and overall pure tone averages (PTA) for
      the population were 67.9, 82.1, and 74.9 dB hearing level, respectively. Mean
      word recognition score (WRS) was 57.6% and deteriorated with increasing PTA (P =
      .0002). Asymmetry, defined by a 10-dB difference at two frequencies, was present
      in 39.2% of the sample, and WRS asymmetry, defined as a difference of 12% in WRS
      between ears, was present in 33.0% of the sample. Retrocochlear evaluation did
      not identify pathology in any of the cases tested. In the poorer hearing ear,
      average decline in PTA per year was 2.9 dB. CONCLUSIONS: In individuals >95 years
      of age, hearing loss was universal, moderately severe to profound in magnitude,
      and associated with substantial loss of speech recognition. Hearing loss
      progresses at a rate greater than for younger cohorts. In this "oldest old"
      population, asymmetry of loss and WRS was common and is not indicative of
      retrocochlear pathology. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1630-1632, 2016.

PMID- 27040358
TI  - Response to Letter to the Editor Re: "Effect of education on non-specific neck
      and low back pain: A meta-analysis of randomized controlled trials".

PMID- 27040357
TI  - Endogenous TWEAK is critical for regulating the function of mouse uterine natural
      killer cells in an immunological model of pregnancy loss.
AB  - Uterine natural killer (uNK) cells are the most abundant lymphocyte population in
      the feto-maternal interface during early gestation, and uNK cells play a
      significant role in the establishment and maintenance of pregnancy-related
      vascularization, as well as in tolerance to the fetus. Tumour necrosis factor
      like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor
      inducible molecule (Fn14), are involved in preventing local cytotoxicity and
      counterbalancing the cytotoxic function of uNK cells. Here, we studied the
      regulation of TWEAK/Fn14-mediated innate immunity in the uterus using a
      lipopolysaccharide (LPS)-induced model of abortion in pregnant mice.
      Specifically, we detected the expression of TWEAK and Fn14 in the uterus and in
      uNK cells following LPS treatment. Our results revealed that TWEAK and Fn14 are
      expressed by uNK cells in pregnant mice; in particular, it appears that the
      cytokine TWEAK is primarily derived from uNK cells. Interestingly, the down
      regulation of TWEAK in uNK cells and the up-regulation of the Fn14 receptor in
      the uterus in LPS-treated mice may contribute to the disruption of decidual
      homeostasis by altering uNK cell cytotoxicity - ultimately leading to fetal
      rejection. In conclusion, the present study strongly suggests that the TWEAK-Fn14
      axis in uNK cells is involved in maintaining the tolerance necessary for
      successful pregnancy. 

PMID- 27040359
TI  - Current patient and healthcare worker attitudes to eHealth and the personally
      controlled electronic health record in major hospitals.
AB  - BACKGROUND: The current health system in Australia is comprised of both
      electronic- and paper-based medical records. The Federal Government has approved
      funding for the development of an individual health identifier and a universally
      adopted online health repository. AIMS: To determine attitudes and beliefs of
      patients and healthcare workers regarding the use of stored medical information
      and the personally controlled electronic health record (PCEHR) in selected major
      hospitals in Victoria. METHODS: Qualitative survey of patients and healthcare
      workers (n = 600 each group) conducted during 2014 across five major hospitals in
      Melbourne to measure the awareness, attitudes and barriers to electronic health
      and the PCEHR. RESULTS: Of the patients, 93.3% support the concept of a shared
      electronic healthcare record, 33.7% were aware of the PCEHR and only 11% had
      registered. The majority of healthcare workers believed that the presence of a
      shared health record would result in an increased appropriateness of care and
      patient safety by reducing adverse drug events and improving the timeliness of
      care provided. However, only 46% of healthcare workers were aware of the PCEHR.
      CONCLUSIONS: This study provides a baseline evaluation of perceptions surrounding
      eHealth and PCHER in acute health services in five metropolitan centres. While
      there appears to be a readiness for adoption of these strategies for healthcare
      documentation, patients require motivation to register for the PCEHR, and
      healthcare workers require more information on the potential benefits to them to
      achieve more timely and efficient care.

PMID- 27040360
TI  - Zooming in on the genesis of atherosclerotic plaque microcalcifications.
AB  - Epidemiological evidence conclusively demonstrates that calcium burden is a
      significant predictor of cardiovascular morbidity and mortality; however, the
      underlying mechanisms remain largely unknown. These observations have challenged
      the previously held notion that calcification serves to stabilize the
      atherosclerotic plaque. Recent studies have shown that microcalcifications that
      form within the fibrous cap of the plaques lead to the accrual of plaque
      destabilizing mechanical stress. Given the association between calcification
      morphology and cardiovascular outcomes, it is important to understand the
      mechanisms leading to calcific mineral deposition and growth from the earliest
      stages. We highlight the open questions in the field of cardiovascular
      calcification and include a review of the proposed mechanisms involved in
      extracellular vesicle-mediated mineral deposition.

PMID- 27040361
TI  - Iron Together with Lipid Downregulates Protein Levels of Ceruloplasmin in
      Macrophages Associated with Rapid Foam Cell Formation.
AB  - AIM: Iron accumulation in foam cells was previously shown to be involved in
      atherogenesis. However, the mechanism for iron accumulation was not clarified.
      Ceruloplasmin (Cp) is an important factor in cellular iron efflux and was found
      to be downregulated in atherosclerotic plaques in our previous study. The current
      study is to investigate the role of Cp in atherosclerosis. METHODS: We used
      RAW264.7 cells, a well-accepted cell model of atherosclerosis, which were treated
      with lipopolysaccharides (LPS), ferric ammonium citrate (FAC) or deferoxamine,
      and oxidized low density lipoprotein (ox-LDL) to detect the regulation of Cp and
      its influence in iron efflux and lipid accumulation using biochemical and
      histological assays. RESULTS: Our results showed that the Cp protein level
      increased after 200-MUM FAC treatment in LPS-activated RAW264.7 cells. Ox-LDL
      treatment (50 MUg/ml) moderately reduced both mRNA and protein levels and
      ferroxidase activity of Cp (p<0.05). No significant difference was observed in
      the expression of ferritin and ferroportin, two important iron-related proteins
      for iron storage and efflux, respectively, after ox-LDL treatment. However, co
      treatment with ox-LDL and FAC drastically reduced the expression of Cp.
      Accordingly, the ferroxidase activities simultaneously decreased, whereas the
      protein levels of Ft and Fpn1 significantly increased, indicating further iron
      accumulation. Moreover, co-treatment with FAC and ox-LDL enhanced the
      accumulation of cholesterol compared with ox-LDL-only treatment to trigger
      apoptosis. CONCLUSION: Our findings suggest that physiological interaction of
      iron and lipid obstructs iron efflux and accelerates the lipid accumulation in
      macrophages during foam cell formation, which implicates the role of iron in the
      pathology of atherosclerosis.

PMID- 27040362
TI  - Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients
      with Low Baseline Cholesterol Levels.
AB  - AIM: The efficacy of statin therapy in inducing coronary plaque regression may
      depend on baseline cholesterol levels. We aimed to determine the efficacy of
      statin therapy in inducing coronary plaque regression in statin-naive patients
      with low cholesterol levels using serial intravascular ultrasound (IVUS) data
      from the treatment with statin on atheroma regression evaluated by virtual
      histology IVUS (TRUTH) study. METHODS: The TRUTH study is a prospective,
      multicenter trial, comparing the efficacies of pitavastatin and pravastatin in
      coronary plaque regression in 164 patients. All patients were statin-naive and
      received statin therapy only after study enrollment. The primary endpoint was the
      observation of coronary plaque progression, despite statin therapy. RESULTS:
      Serial IVUS data, at baseline and after an 8-month follow-up, were available for
      119 patients. The patients were divided into three groups based on non-high
      density lipoprotein cholesterol (HDL-C) levels-low: <=140 mg/dl, n=38; moderate:
      141-169 mg/dl, n=42; and high: >=170 mg/dl, n=39. Coronary plaque progression was
      noted in the low cholesterol group, whereas plaque regression was noted in the
      moderate and high cholesterol groups [%Deltaplaque volume: 2.3+/-7.4 vs. -2.7+/-
      10.7 vs. -3.2+/-7.5, p=0.004 (analysis of variance)]. After adjusting for all
      variables, a low non-HDL-C level (<=140 mg/dl) was identified as an independent
      predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence
      interval, 1.5-9.1, p=0.004]. CONCLUSION: Serial IVUS data analysis indicated that
      statin therapy was less effective in inducing coronary plaque regression in
      patients with low cholesterol levels but more effective in those with high
      cholesterol levels at baseline.University Hospital Medical Information Network
      (UMIN) (UMIN ID: C000000311).

PMID- 27040363
TI  - Measles Inclusion-Body Encephalitis: Neuronal Phosphorylated Tau Protein is
      Present in the Biopsy but not in the Autoptic Specimens of the Same Patient.

PMID- 27040364
TI  - A case of autoimmune progesterone dermatitis characterized by grouped small
      vesicles.

PMID- 27040365
TI  - Nanofaceting as a stamp for periodic graphene charge carrier modulations.
AB  - The exceptional electronic properties of monatomic thin graphene sheets triggered
      numerous original transport concepts, pushing quantum physics into the realm of
      device technology for electronics, optoelectronics and thermoelectrics. At the
      conceptual pivot point is the particular two-dimensional massless Dirac fermion
      character of graphene charge carriers and its volitional modification by
      intrinsic or extrinsic means. Here, interfaces between different electronic and
      structural graphene modifications promise exciting physics and functionality, in
      particular when fabricated with atomic precision. In this study we show that
      quasiperiodic modulations of doping levels can be imprinted down to the nanoscale
      in monolayer graphene sheets. Vicinal copper surfaces allow to alternate graphene
      carrier densities by several 10(13) carriers per cm(2) along a specific copper
      high-symmetry direction. The process is triggered by a self-assembled copper
      faceting process during high-temperature graphene chemical vapor deposition,
      which defines interfaces between different graphene doping levels at the atomic
      level. 

PMID- 27040366
TI  - In situ microscopy of the self-assembly of branched nanocrystals in solution.
AB  - Solution-phase self-assembly of nanocrystals into mesoscale structures is a
      promising strategy for constructing functional materials from nanoscale
      components. Liquid environments are key to self-assembly since they allow
      suspended nanocrystals to diffuse and interact freely, but they also complicate
      experiments. Real-time observations with single-particle resolution could have
      transformative impact on our understanding of nanocrystal self-assembly. Here we
      use real-time in situ imaging by liquid-cell electron microscopy to elucidate the
      nucleation and growth mechanism and properties of linear chains of octapod-shaped
      nanocrystals in their native solution environment. Statistical mechanics
      modelling based on these observations and using the measured chain-length
      distribution clarifies the relative importance of dipolar and entropic forces in
      the assembly process and gives direct access to the interparticle interaction.
      Our results suggest that monomer-resolved in situ imaging combined with modelling
      can provide unprecedented quantitative insight into the microscopic processes and
      interactions that govern nanocrystal self-assembly in solution. 

PMID- 27040367
TI  - Assessing the importance of four sandfly species (Diptera: Psychodidae) as
      vectors of Leishmania mexicana in Campeche, Mexico.
AB  - Localized cutaneous leishmaniasis represents a public health problem in many
      areas of Mexico, especially in the Yucatan Peninsula. An understanding of vector
      ecology and bionomics is of great importance in evaluations of the transmission
      dynamics of Leishmania parasites. A field study was conducted in the county of
      Calakmul, state of Campeche, during the period from November 2006 to March 2007.
      Phlebotomine sandfly vectors were sampled using Centers for Disease Control light
      traps, baited Disney traps and Shannon traps. A total of 3374 specimens were
      captured in the two villages of Once de Mayo (93.8%) and Arroyo Negro (6.1%). In
      Once de Mayo, the most abundant species were Psathyromyia shannoni, Lutzomyia
      cruciata, Bichromomyia olmeca olmeca and Psychodopygus panamensis (all: Diptera:
      Psychodidae). The Shannon trap was by far the most efficient method of
      collection. The infection rate, as determined by Leishmania mexicana-specific
      polymerase chain reaction, was 0.3% in Once de Mayo and infected sandflies
      included Psy. panamensis, B. o. olmeca and Psa. shannoni. There were significant
      differences in human biting rates across sandfly species and month of sampling.
      Ecological niche modelling analyses showed an overall overlap of 39.1% for the
      four species in the whole state of Campeche. In addition, the finding of nine
      vector-reservoir pairs indicates a potential interaction. The roles of the
      various sandfly vectors in Calakmul are discussed.

PMID- 27040368
TI  - Phylogenetic analysis of beta-xylanase SRXL1 of Sporisorium reilianum and its
      relationship with families (GH10 and GH11) of Ascomycetes and Basidiomycetes.
AB  - In this paper, the amino acid sequence of the beta-xylanase SRXL1 of Sporisorium
      reilianum, which is a pathogenic fungus of maize was used as a model protein to
      find its phylogenetic relationship with other xylanases of Ascomycetes and
      Basidiomycetes and the information obtained allowed to establish a hypothesis of
      monophyly and of biological role. 84 amino acid sequences of beta-xylanase
      obtained from the GenBank database was used. Groupings analysis of higher-level
      in the Pfam database allowed to determine that the proteins under study were
      classified into the GH10 and GH11 families, based on the regions of highly
      conserved amino acids, 233-318 and 180-193 respectively, where glutamate residues
      are responsible for the catalysis. 

PMID- 27040369
TI  - IR-Live: fabrication of a low-cost plastic microfluidic device for infrared
      spectromicroscopy of living cells.
AB  - Water is a strong mid-infrared absorber, which has hindered the full exploitation
      of label-free and non-invasive infrared (IR) spectromicroscopy techniques for the
      study of living biological samples. To overcome this barrier, many researchers
      have built sophisticated fluidic chambers or microfluidic chips wherein the depth
      of the liquid medium in the sample compartment is limited to 10 MUm or less. Here
      we report an innovative and simple way to fabricate plastic devices with infrared
      transparent view-ports enabling infrared spectromicroscopy of living biological
      samples; therefore the device is named "IR-Live". Advantages of this approach
      include lower production costs, a minimal need to access a micro-fabrication
      facility, and unlimited mass or waste exchange for the living samples surrounding
      the view-port area. We demonstrate that the low-cost IR-Live in combination with
      microfluidic perfusion techniques enables long term (>60 h) cell culture, which
      broadens the capability of IR spectromicroscopy for studying living biological
      samples. To illustrate this, we first applied the device to study protein and
      lipid polarity in migrating REF52 fibroblasts by collecting 2-dimensional
      spectral chemical maps at a micrometer spatial resolution. Then, we demonstrated
      the suitability of our approach to study dynamic cellular events by collecting a
      time series of spectral maps of U937 monocytes during the early stage of cell
      attachment to a bio-compatible surface.

PMID- 27040370
TI  - A facile route to old and new cyclophanes via self-assembly and capture.
AB  - Cyclophanes are a venerable class of macrocyclic and/or cage compounds that often
      feature high strain, unusual conformations and quite surprising properties, many
      of which are legendary in physical organic chemistry. However, the discovery of
      new, diverse cyclophanes and derivatives has been hindered by syntheses that are
      traditionally low-yielding, requiring long reaction times, laborious purification
      steps and often extreme conditions. Herein, we demonstrate a new self-assembly
      route to a variety of discrete cyclic and caged disulfide structures, which can
      then be kinetically captured upon sulfur extrusion at room temperature to give a
      diversity of new thioether (hetera)cyclophanes in high yield. In addition to the
      synthesis of novel macrocycles (dimers through hexamers), this process provides
      an improved route to a known macrobicyclic trithiacyclophane. This technique also
      enables the facile isolation of a tetrahedral macrotricyclic tetrathiacyclophane
      in two steps at an ambient temperature. 

PMID- 27040371
TI  - Regulatory T-cell-intrinsic amphiregulin is dispensable for suppressive function.

PMID- 27040372
TI  - Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of
      randomized clinical trials.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU) is defined by itchy hives,
      angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that
      affects mast cell and basophil function, is a promising new treatment option. As
      of now, however, the efficacy and safety of different doses of omalizumab used in
      clinical trials for CSU have not been systematically analyzed and summarized.
      OBJECTIVE: We sought to assess the efficacy and safety of different doses of
      omalizumab for the treatment of CSU in a meta-analysis of clinical trial results.
      METHODS: Suitable trials were identified by searching PubMed, Medline, Embase,
      and Web of Science databases and with the help of omalizumab's manufacturers.
      Only double-blind, randomized, placebo-controlled studies with omalizumab-treated
      versus placebo-treated patients with CSU were included in this analysis. RESULTS:
      We identified 7 randomized, placebo-controlled studies with 1312 patients with
      CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had significantly
      reduced weekly itch and weekly wheal scores compared with the placebo group.
      Omalizumab's effects were dose dependent, with the strongest reduction in weekly
      itch and weekly wheal scores observed with 300 mg. Rates of complete response
      were significantly higher in the omalizumab group (relative risk, 4.55; P <
      .00001) and dose dependent, with the highest rates in the 300-mg group. Rates of
      patients with adverse events were similar in the omalizumab and placebo groups.
      CONCLUSION: This meta-analysis provides high-quality evidence for the efficacy
      and safety of omalizumab in patients with CSU and for treating these patients
      with 300 mg of omalizumab every 4 weeks.

PMID- 27040373
TI  - Sensitization of a child to Cyanobacteria after recreational swimming in a lake.

PMID- 27040374
TI  - Dysregulation of proinflammatory versus anti-inflammatory human TH17 cell
      functionalities in the autoinflammatory Schnitzler syndrome.
AB  - BACKGROUND: TH17 cells have so far been considered to be crucial mediators of
      autoimmune inflammation. Two distinct types of TH17 cells have been described
      recently, which differed in their polarization requirement for IL-1beta and in
      their cytokine repertoire. Whether these distinct TH17 phenotypes translate into
      distinct TH17 cell functions with implications for human health or disease has
      not been addressed yet. OBJECTIVE: We hypothesized the existence of
      proinflammatory and anti-inflammatory human TH17 cell functions based on the
      differential expression of IL-10, which is regulated by IL-1beta. Considering the
      crucial role of IL-1beta in the pathogenesis of autoinflammatory syndromes, we
      hypothesized that IL-1beta mediates the loss of anti-inflammatory TH17 cell
      functionalities in patients with Schnitzler syndrome, an autoinflammatory
      disease. METHODS: To assess proinflammatory versus anti-inflammatory TH17 cell
      functions, we performed suppression assays and tested the effects of IL-1beta
      dependent and independent TH17 subsets on modulating proinflammatory cytokine
      secretion by monocytes. Patients with Schnitzler syndrome were analyzed for
      changes in TH17 cell functions before and during therapy with IL-1beta-blocking
      drugs. RESULTS: Both TH17 cell subsets differ in their ability to suppress T-cell
      proliferation and their ability to modulate proinflammatory cytokine production
      by antigen-presenting cells because of their differential IL-10 expression
      properties. In patients with Schnitzler syndrome, systemic overproduction of IL
      1beta translates into a profound loss of anti-inflammatory TH17 cell
      functionalities, which can be reversed by anti-IL-1beta treatment. CONCLUSION: IL
      1beta signaling determines the differential expression pattern of IL-10, which is
      necessary and sufficient to induce proinflammatory versus anti-inflammatory TH17
      cell functions. Our data introduce TH17 cell subsets as novel players in
      autoinflammation and thus novel therapeutic targets in autoinflammatory syndromes
      including other IL-1beta mediated diseases. This demonstrates for the first time
      alterations in the adaptive immune system in patients with autoinflammatory
      syndromes.

PMID- 27040375
TI  - Association of trihalomethanes in tap water with house dust mite allergen
      sensitization in US adolescents.

PMID- 27040376
TI  - Significant light absorption enhancement in silicon thin film tandem solar cells
      with metallic nanoparticles.
AB  - Enhancing the light absorption in microcrystalline silicon bottom cell of a
      silicon-based tandem solar cell for photocurrent matching holds the key to
      achieving the overall solar cell performance breakthroughs. Here, we present a
      concept for significantly improving the absorption of both subcells
      simultaneously by simply applying tailored metallic nanoparticles both on the top
      and at the rear surfaces of the solar cells. Significant light absorption
      enhancement as large as 56% has been achieved in the bottom subcells. More
      importantly the thickness of the microcrystalline layer can be reduced by 57%
      without compromising the optical performance of the tandem solar cell, providing
      a cost-effective strategy for high performance tandem solar cells. 

PMID- 27040377
TI  - Fabrication of slender elastic shells by the coating of curved surfaces.
AB  - Various manufacturing techniques exist to produce double-curvature shells,
      including injection, rotational and blow molding, as well as dip coating.
      However, these industrial processes are typically geared for mass production and
      are not directly applicable to laboratory research settings, where adaptable,
      inexpensive and predictable prototyping tools are desirable. Here, we study the
      rapid fabrication of hemispherical elastic shells by coating a curved surface
      with a polymer solution that yields a nearly uniform shell, upon polymerization
      of the resulting thin film. We experimentally characterize how the curing of the
      polymer affects its drainage dynamics and eventually selects the shell thickness.
      The coating process is then rationalized through a theoretical analysis that
      predicts the final thickness, in quantitative agreement with experiments and
      numerical simulations of the lubrication flow field. This robust fabrication
      framework should be invaluable for future studies on the mechanics of thin
      elastic shells and their intrinsic geometric nonlinearities. 

PMID- 27040378
TI  - Implications of genotypic differences in the generation of a urinary metabolomics
      radiation signature.
AB  - The increased threat of radiological terrorism and accidental nuclear exposures,
      together with increased usage of radiation-based medical procedures, has made
      necessary the development of minimally invasive methods for rapid identification
      of exposed individuals. Genetically predisposed radiosensitive individuals
      comprise a significant number of the population and require specialized attention
      and treatments after such events. Metabolomics, the assessment of the collective
      small molecule content in a given biofluid or tissue, has proven effective in the
      rapid identification of radiation biomarkers and metabolic perturbations. To
      investigate how the genotypic background may alter the ionizing radiation (IR)
      signature, we analyzed urine from Parp1(-/-) mice, as a model radiosensitive
      genotype, exposed to IR by utilizing the analytical power of liquid
      chromatography coupled with mass spectrometry (LC-MS), as urine has been
      thoroughly investigated in wild type (WT) mice in previous studies from our
      laboratory. Samples were collected at days one and three after irradiation, time
      points that are important for the early and efficient triage of exposed
      individuals. Time-dependent perturbations in metabolites were observed in the
      tricarboxylic acid pathway (TCA). Other differentially excreted metabolites
      included amino acids and metabolites associated with dysregulation of energy
      metabolism pathways. Time-dependent apoptotic pathway activation between WT and
      mutant mice following IR exposure may explain the altered excretion patterns,
      although the origin of the metabolites remains to be determined. This first
      metabolomics study in urine from radiation exposed genetic mutant animal models
      provides evidence that this technology can be used to dissect the effects of
      genotoxic agents on metabolism by assessing easily accessible biofluids and
      identify biomarkers of radiation exposure. Applications of metabolomics could be
      incorporated in the future to further elucidate the effects of IR on the
      metabolism of Parp1(-/-) genotype by assessing individual tissues.

PMID- 27040379
TI  - Effect of Follicle Size on In Vitro Maturation of Pre-Pubertal Porcine Cumulus
      Oocyte Complexes.
AB  - Very small follicles (<3.0 mm diameter) are over-represented on the surface of
      ovaries of non-cycling pigs, and the oocytes collected from these follicles
      generally have reduced developmental competence in vitro. This study examined the
      effect of follicle size on the nuclear maturation (n = 608), the potential of
      parthenogenetic activation (n = 243) and the cyclic AMP (cAMP) content of pre
      pubertal porcine oocytes (n = 480). In addition, the influence of follicle size
      on steroid hormone synthesis was analysed. Cumulus oocyte complexes (COCs)
      flushed from small (2.5-4.0 mm) or large (4.5-6.0 mm) ovarian follicles were
      cultured for 0, 28 and 46 h. After 46 h of IVM, a greater proportion of oocytes
      from 4.5- to 6.0-mm follicles reach metaphase II (MII) compared with those from
      follicles with 2.5-4.0 mm of diameter (96.1 vs 77.0%, respectively; p < 0.001).
      Parthenogenetic activation of oocytes from large follicles produced higher
      developmental rates than oocytes from large follicles (p < 0.05). At 28 h, the
      IVM medium with oocytes from large follicles contained significantly more 17beta
      oestradiol (E2 ) than the medium with oocytes from small follicles (5.55 vs 3.45
      ng/ml, respectively; p < 0.05) and at 46 h, the medium with oocytes from small
      follicles contained significantly more progesterone (P4 ) than the medium with
      oocytes from large follicles (276.7 vs 108.2 ng/ml, respectively, p < 0.05).
      Porcine oocytes from large follicles have higher nuclear and cytoplasmic
      maturation capacities, but the differences did not appear to be cAMP-mediated.
      Our findings also suggest that COCs from small follicles undergo more intensive
      luteinization than COCs from large follicles. The results show that oocytes from
      follicles with a diameter greater than 4.0 mm are more suitable for in vitro
      studies. 

PMID- 27040380
TI  - Effect of reclassification of the IMDC model in patients with metastatic renal
      cell carcinoma treated with targeted therapy in the first-line and second-line
      settings.
AB  - PURPOSE: To investigate the prognostic effect of the International Metastatic
      Renal Cell Carcinoma Database Consortium (IMDC) model reclassification after
      targeted therapy administration in metastatic renal cell carcinoma (mRCC).
      PATIENTS AND METHOD: A total of 245 mRCC patients treated with targeted therapy
      are included. The IMDC model reclassification is performed at 1 month after
      treatment induction of both first-line and second-line targeted therapy. RESULTS:
      Of the 245 patients, 74 (30.2%) are divided into different risk groups by the
      IMDC model reclassification after first-line targeted therapy, and patients newly
      classified with intermediate risk tend to have better overall survival than those
      remaining in the primary poor-risk group (P = 0.018). Of the 119 patients treated
      with subsequent second-line targeted therapy, 25 (21.0%) are divided into
      different risk groups by the IMDC model reclassification after second-line
      targeted therapy, and patients newly classified with poor risk tend to have
      increased all-cause mortality compared with those remaining in the primary
      intermediate-risk group (P = 0.007), whereas patients newly classified with
      intermediate risk tend to have better overall survival than those remaining in
      the primary poor-risk group (P = 0.034). CONCLUSION: Approximately a quarter of
      the mRCC patients are classified into different risk groups of the IMDC model
      following targeted therapy administration in the first-line and second-line
      settings. There is a significant difference in overall survival of subgroups
      after the IMDC model reclassifications.

PMID- 27040382
TI  - Gastrointestinal Endoscopy-Assisted Minimally Invasive Surgery for Superficial
      Cancer of the Uvula.
AB  - Previous studies reported that endoscopic resection is effective for the
      treatment of superficial pharyngeal cancers, as for digestive tract cancers.
      However, the optimal treatment for superficial cancer of the uvula has not been
      established because of the rarity of this condition. We present two male patients
      in their 70s with superficial cancer of the uvula, detected with upper
      gastrointestinal endoscopy. Both patients underwent surgical resection of the
      uvula under general anesthesia. The extent of the lesions was determined by means
      of gastrointestinal endoscopy by using magnifying observation with narrow-band
      imaging, enabling the performance of minimally invasive surgery. Endoscopic
      submucosal dissection was performed to achieve en bloc resection of the
      intramucosal carcinoma that had infiltrated the area adjacent to the uvula.
      Gastrointestinal endoscopists should carefully examine the laryngopharynx to
      avoid missing superficial cancers. Our minimally invasive treatment for
      superficial cancer of the uvula had favorable postoperative outcomes, and
      prevented postoperative loss of breathing, swallowing, and articulation
      functions. 

PMID- 27040381
TI  - Prostate cancer risk stratification with magnetic resonance imaging.
AB  - In recent years, multiparametric magnetic resonance imaging (mpMRI) has shown
      promise for prostate cancer (PCa) risk stratification. mpMRI, often followed by
      targeted biopsy, can be used to confirm low-grade disease before enrollment in
      active surveillance. In patients with intermediate or high-risk PCa, mpMRI can be
      used to inform surgical management. mpMRI has sensitivity of 44% to 87% for
      detection of clinically significant PCa and negative predictive value of 63% to
      98% for exclusion of significant disease. In addition to tumor identification,
      mpMRI has also been shown to contribute significant incremental value to
      currently used clinical nomograms for predicting extraprostatic extension. In
      combination with conventional clinical criteria, accuracy of mpMRI for prediction
      of extraprostatic extension ranges from 92% to 94%, significantly higher than
      that achieved with clinical criteria alone. Supplemental sequences, such as
      diffusion-weighted imaging and dynamic contrast-enhanced imaging, allow
      quantitative evaluation of cancer-suspicious regions. Apparent diffusion
      coefficient appears to be an independent predictor of PCa aggressiveness.
      Addition of apparent diffusion coefficient to Epstein criteria may improve
      sensitivity for detection of significant PCa by as much as 16%. Limitations of
      mpMRI include variability in reporting, underestimation of PCa volume and failure
      to detect clinically significant disease in a small but significant number of
      cases.

PMID- 27040383
TI  - Nuclear factor-kappaB-dependent microRNA-130a upregulation promotes cervical
      cancer cell growth by targeting phosphatase and tensin homolog.
AB  - Nuclear factor-kappaB (NF-kappaB) may activate a series of gene transcription
      control cellular signaling pathways whose products are components in a wide range
      of biological processes. MicroRNAs, a group of non-coding endogenous ones, may
      regulate gene expression and plays specific roles in tumorigenesis. Using human
      cervical cancer cell lines, we explored whether NF-kappaB regulates the
      expression of microRNA-130a (miR-130a) through binding elements in the miR-130a
      promoter region. We found that miR-130a accelerates cervical cancer cell
      proliferation by targeting the phosphatase and tensin homolog on chromosome 10
      (PTEN). Further, NF-kappaB activates both HeLa and CaSki cell growth by
      upregulating miR-130a. In addition, by targeting PTEN 3' untranslated region, miR
      130a might increase cell growth and initiate protein kinase B (AKT) pathway
      activation. Lastly, PTEN protein was upregulated in response to NF-kappaB
      overexpression and downregulated in response to NF-kappaB inhibition. Compared to
      total AKT protein level, p-AKT was downregulated by NF-kappaB overexpression
      while upregulated by NF-kappaB inhibition, indicating PTEN pathway activated and
      affected by NF-kappaB. Taken together, our findings shed new light on the NF
      kappaB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the
      carcinogenesis of cervical cancer.

PMID- 27040384
TI  - Tanshinone IIA inhibits human esophageal cancer cell growth through miR-122
      mediated PKM2 down-regulation.
AB  - Pyruvate kinase M2 (PKM2) plays a pivotal role in the growth, survival and
      metabolic reprogramming of cancer cells. Here, we presented for the first time
      that tanshinone IIA inhibited human esophagus cancer cell growth through miR-122
      mediated PKM2 down-regulation pathway. Tanshinone IIA inhibited cell
      proliferation and induced cell cycle arrest in S phase in human Ec109 cells. As
      expected, tanshinone IIA down-regulated PKM2 mRNA and protein expression in Ec109
      cells. Given these findings, we further investigated microRNAs regulation of PKM2
      and confirmed miR-122 for targeting PKM2. Moreover, we found that tanshinone IIA
      induced up-regulation of miR-122 expression inhibited PKM2 expression in Ec109
      cells. Meanwhile, tanshinone IIA inhibited proliferation through miR122-medated
      PKM2 down-regulation. It was demonstrated that the anticancer activity of
      tanshinone IIA was targeted at metabolic regulation of miR-122/PKM2 in human
      esophagus cancer cells. Taken together, our results revealed tanshinone IIA
      targeting at PKM2-mediated metabolic reprogramming play an important role in
      inhibition of esophageal cancer cell growth.

PMID- 27040385
TI  - Activation of Toll-Like Receptors 2 by High-Mobility Group Box 1 in Monocytes
      from Patients with Ischemic Stroke.
AB  - BACKGROUND: Stroke is a leading cause of death all around the world, and ischemic
      stroke is considered to be the most common stroke type. Toll-like receptors
      (TLRs) are important molecules for detection of both pathogen invasion and tissue
      damage. In this regard, the purpose of this study was to assess the expression
      level of TLR2 on monocytes in patients with ischemic stroke and to evaluate the
      expression change profile following high-mobility group box 1 (HMGB1)
      stimulation. METHODS: A total of 30 patients with ischemic stroke were enrolled
      from November 2013 to September 2014. The real-time PCR and ELISA assays were
      applied to detect the concentrations of TLR2 mRNAs. RESULTS: TLR2 expression was
      found to be increased in patients with ischemic stroke, as compared to the
      healthy control group (P<0.001). Also, anti-TLR2 antibodies were able to decrease
      the expression levels of IL-17, IL-6 and IL-33. This result implies that the
      enhanced TLR2 pathway and Th17 cell polarization may be due to HMGB1 stimulation
      in ischemic stroke. CONCLUSION: Further clinical studies are needed for
      development of a new treatment strategy to inhibit the HMGB1 pathway, thus
      preventing the inflammation in ischemic stroke patients.

PMID- 27040386
TI  - Statistical shape analysis of the human spleen geometry for probabilistic
      occupant models.
AB  - Statistical shape models are an effective way to create computational models of
      human organs that can incorporate inter-subject geometrical variation. The main
      objective of this study was to create statistical mean and boundary models of the
      human spleen in an occupant posture. Principal component analysis was applied to
      fifteen human spleens in order to find the statistical modes of variation, mean
      shape, and boundary models. A landmark sliding approach was utilized to refine
      the landmarks to obtain a better shape correspondence and create a better
      representation of the underlying shape contour. The first mode of variation was
      found to be the overall volume, and it accounted for 69% of the total variation.
      The mean model and boundary models could be used to develop probabilistic finite
      element (FE) models which may identify the risk of spleen injury during vehicle
      collisions and consequently help to improve automobile safety systems.

PMID- 27040387
TI  - The impact of valve simplifications on left ventricular hemodynamics in a three
      dimensional simulation based on in vivo MRI data.
AB  - Left ventricle (LV) fluid dynamics and the function of its valves have a crucial
      impact on clinical diagnosis, treatment and prosthesis design. In this paper, we
      simulated left ventricular flow using 3D computational fluid dynamics (CFD) based
      on geometrical and deformational information obtained from MRI. Time variant
      smoothed LV shapes were extracted from MR images. Corresponding deformation data
      was interpolated using a cubic-spline interpolation. To evaluate valve influence
      on LV flow, we compared two planar valve models: physiologically corrected
      gradually opening/closing model and a simple on/off model. Endocardial
      displacement was applied to fluid boundary using fluid-structure interaction
      (FSI) approach. Arbitrary Lagrangian-Eulerian (ALE) formulation was used for
      unsteady incompressible viscous Newtonian blood flow in the fluid domain.
      Comparison of results for LV flow with two valve models demonstrated a clear
      distinction between pressure distribution, velocity distribution, vortex
      formation/growth/vanishing and energy dissipation especially in the filling
      phase. Consequently, LV flow simulation by ignoring geometrical details of
      valves' model may lead to non-realistic results in some aspects.

PMID- 27040388
TI  - Study of cardiovascular function using a coupled left ventricle and systemic
      circulation model.
AB  - To gain insight into cardio-arterial interactions, a coupled left ventricle
      systemic artery (LV-SA) model is developed that incorporates a three-dimensional
      finite-strain left ventricle (LV), and a physiologically-based one-dimensional
      model for the systemic arteries (SA). The coupling of the LV model and the SA
      model is achieved by matching the pressure and the flow rate at the aortic root,
      i.e. the SA model feeds back the pressure as a boundary condition to the LV
      model, and the aortic flow rate from the LV model is used as the input for the SA
      model. The governing equations of the coupled system are solved using a combined
      immersed-boundary finite-element (IB/FE) method and a Lax-Wendroff scheme. A
      baseline case using physiological measurements of healthy subjects, and four
      exemplar cases based on different physiological and pathological scenarios are
      studied using the LV-SA model. The results of the baseline case agree well with
      published experimental data. The four exemplar cases predict varied pathological
      responses of the cardiovascular system, which are also supported by clinical
      observations. The new model can be used to gain insight into cardio-arterial
      interactions across a range of clinical applications.

PMID- 27040389
TI  - A comparison study of local dynamic stability measures of daily life walking in
      older adult community-dwelling fallers and non-fallers.
AB  - In the present study we compared the performance of three different estimations
      of local dynamic stability lambda to distinguish between the dynamics of the
      daily-life walking of elderly fallers and non-fallers. The study re-analyses
      inertial sensor data of 3-days daily-life activity originally described by Weiss
      et al. (2013). The data set contains inertial sensor data from 39 older persons
      who reported less than 2 falls and 31 older persons who reported two or more
      falls the previous year. 3D-acceleration and 3D-velocity signals from walking
      epochs of 50s were used to reconstruct a state space using three different
      methods. Local dynamic stability was estimated with the algorithms proposed by
      Rosenstein et al. (1993), Kantz (1994), and Ihlen et al. (2012a). Median lambdas
      assessed by Ihlen's and Kantz' algorithms discriminated better between elderly
      fallers and non-fallers (highest AUC=0.75 and 0.73) than Rosenstein's algorithm
      (highest AUC=0.59). The present results suggest that the ability of lambda to
      distinguish between fallers and non-fallers is dependent on the parameter setting
      of the chosen algorithm. Further replication in larger samples of community
      dwelling older persons and different patient groups is necessary before including
      the suggested parameter settings in fall risk assessment and prediction models.

PMID- 27040390
TI  - Compressive and shear hip joint contact forces are affected by pediatric obesity
      during walking.
AB  - Obese children exhibit altered gait mechanics compared to healthy-weight children
      and have an increased prevalence of hip pain and pathology. This study sought to
      determine the relationships between body mass and compressive and shear hip joint
      contact forces during walking. Kinematic and kinetic data were collected during
      treadmill walking at 1ms(-1) in 10 obese and 10 healthy-weight 8-12 year-olds. We
      estimated body composition, segment masses, lower-extremity alignment, and
      femoral neck angle via radiographic images, created personalized musculoskeletal
      models in OpenSim, and computed muscle forces and hip joint contact forces. Hip
      extension at mid-stance was 9 degrees  less, on average, in the obese children
      (p<0.001). Hip abduction, knee flexion, and body-weight normalized peak hip
      moments were similar between groups. Normalized to body-weight, peak contact
      forces were similar at the first peak and slightly lower at the second peak
      between the obese and healthy-weight participants. Total body mass explained a
      greater proportion of contact force variance compared to lean body mass in the
      compressive (r(2)=0.89) and vertical shear (perpendicular to the physis acting
      superior-to-inferior) (r(2)=0.84) directions; lean body mass explained a greater
      proportion in the posterior shear direction (r(2)=0.54). Stance-average contact
      forces in the compressive and vertical shear directions increased by 41N and 48N,
      respectively, for every kilogram of body mass. Age explained less than 27% of the
      hip loading variance. No effect of sex was found. The proportionality between hip
      loads and body-weight may be implicated in an obese child's increased risk of hip
      pain and pathology.

PMID- 27040391
TI  - Hyperelastic compressive mechanical properties of the subcalcaneal soft tissue:
      An inverse finite element analysis.
AB  - Finite element (FE) foot models can provide insight into soft tissue internal
      stresses and allow researchers to effectively conduct parametric analyses.
      Accurate plantar soft tissue material properties are essential for the
      development of FE foot models for clinical interventions. The aim of this study
      was to identify the first-order and second-order Ogden hyperelastic material
      properties of the subcalcaneal fat using an inverse FE analysis. The cylindrical
      soft tissue FE model was developed based on a priori in vitro dynamic compression
      experiment. The model simulated a 1Hz triangle wave displacement to apply a
      compressive strain up to 48%. The hyperelastic properties were identified by
      systematically varying the material parameters to minimize the difference between
      the model predicted force and the target experimental data. Optimal material
      properties were obtained (MU1=0.0235kPa and alpha1=12.07 for the first-order
      Ogden model and MU1=-4.629*10(-6)kPa, alpha1=-16.829; MU2=-1.613kPa and alpha2=
      1.043 for the second-order Ogden model). The second-order Ogden model was
      superior in capturing the highly nonlinear force-deformation response when
      compared to the first-order model (root mean square error (RMSE) 0.169N vs.
      0.570N). The material sensitivity analysis indicated that the predicted force was
      strongly affected by the Poisson's ratio (12-fold increase in RMSE when reducing
      Poisson's ratio by 10% from the baseline) and the coefficient alpha1 (3.2-fold
      and 32-fold increase in RMSE for both first-order and second-order Ogden models
      when increasing alpha1 by 10% from the optimal value).

PMID- 27040392
TI  - The Future Is Here: Bundled Payments and International Statistical Classification
      of Diseases, 10th Revision.

PMID- 27040393
TI  - Low c-Kit Expression Level Induced by Stem Cell Factor Does Not Compromise
      Transplantation of Hematopoietic Stem Cells.
AB  - The c-Kit expression level is decreased in regenerating bone marrow, and such
      bone marrow performs poorly when co-transplanted with normal bone marrow. We
      asked whether diminished numbers of c-Kit receptors on hematopoietic stem and
      progenitor cells (HSPCs) after their internalization induced by the binding of
      the cytokine stem cell factor (SCF) would jeopardize transplantability of HSPCs.
      We used a battery of functional assays to evaluate the capacity of HSPCs with
      markedly different c-Kit expression levels to be transplanted. Surprisingly, our
      experiments testing the homing of transplanted HSPCs to bone marrow of recipient
      mice and their short-term and long-term engraftment did not reveal any defects in
      HSPCs with severely reduced numbers of c-Kit receptor molecules. This unexpected
      result can be ascribed to the fact that HSPCs exposed to SCF replace the consumed
      c-Kit receptors rapidly. This article demonstrates that exposure of HSPCs to SCF
      and diminished number of c-Kit receptors in their cell membranes do not
      compromise the capacity of HSPCs to reconstitute damaged hematopoietic tissue.

PMID- 27040394
TI  - Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide
      Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of
      a Multicenter Phase II Study and CIBMTR Outcomes.
AB  - Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning
      regimen for autologous stem cell transplantation (ASCT). This multicenter, phase
      II study examined the safety and efficacy of BuCyE with individually adjusted
      busulfan based on preconditioning pharmacokinetics. The study initially enrolled
      Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years
      but was amended due to high early treatment-related mortality (TRM) in patients >
      65 years. BuCyE outcomes were compared with contemporaneous recipients of
      carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for
      International Blood and Marrow Transplant Research. Two hundred seven subjects
      with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America,
      and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65
      years (n = 17), and patients <= 65 years (n = 186) were 4.5%, 23.5%, and 2.7%,
      respectively. The estimated rates of 2-year progression-free survival (PFS) were
      33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n =
      63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23),
      respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL
      and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched
      analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there
      were no differences in outcomes for NHL. Patients with HL had lower rates of 2
      year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52%
      to 66%), with no differences in TRM or OS. BuCyE provided adequate disease
      control and safety in B cell NHL patients <= 65 years but produced worse PFS in
      HL patients when compared with BEAM.

PMID- 27040395
TI  - Decision Analysis of Postremission Therapy in Cytogenetically Intermediate-Risk
      Acute Myeloid Leukemia: The Impact of FLT3 Internal Tandem Duplication,
      Nucleophosmin, and CCAAT/Enhancer Binding Protein Alpha.
AB  - We performed a decision analysis comparing allogeneic hematopoietic cell
      transplantation (allo-HCT) versus chemotherapy in first complete remission for
      patients with cytogenetically intermediate-risk acute myeloid leukemia, depending
      on the presence or absence of FLT3-internal tandem duplication (ITD),
      nucleophosmin (NPM1), and CCAAT/enhancer binding protein alpha (CEBPA) mutations.
      Adjusted means of the patient-reported EQ-5D index were used as quality-of-life
      (QOL) estimates. In 332 patients for which FLT3-ITD status was available, FLT3
      ITD was present in 60. In 272 patients without FLT3-ITD, NPM1 mutations were
      present in 83. CEBPA biallelic mutations were detected in 53 patients. For
      patients harboring FLT3-ITD, allo-HCT improved life expectancy (LE) (52 versus 32
      months during 10-year observation) and QOL-adjusted life expectancy (QALE, 36
      versus 21). Monte-Carlo simulation identified allo-HCT as the favored strategy in
      100% of simulations. In patients without FLT3-ITD, allo-HCT improved LE/QALE with
      or without NPM1 mutations. However, sensitivity analyses showed that the results
      were not robust enough. For patients harboring CEBPA biallelic mutations,
      chemotherapy was favored (LE, 53 versus 84; QALE, 37 versus 59), whereas, for
      patients with monoallelic mutations or wild-type CEBPA, allo-HCT was favored (LE,
      68 versus 54; QALE, 48 versus 37). Sensitivity analyses did not change the
      results in either group. In conclusion, based on a Markov decision analysis, allo
      HCT was a favored postremission strategy in patients with FLT3-ITD, and
      chemotherapy was favored in patients with biallelic CEBPA mutations. A
      prospective study is warranted to determine the value of allo-HCT, especially in
      FLT3-ITD-negative patients.

PMID- 27040396
TI  - Differential Regulation of CXCL8 Production by Different G Protein Subunits with
      Synergistic Stimulation by Gi- and Gq-Regulated Pathways.
AB  - CXCL8 (also known as interleukin-8 or IL-8) is a proinflammatory chemokine that
      not only modulates the inflammatory and immune responses, but whose upregulation
      is often associated with diseases including various types of cancer. Although
      numerous ligands for G protein-coupled receptors (GPCRs) have been shown to
      stimulate the production of CXCL8, the specificity of the G protein signal
      remains undefined. By expressing the constitutively active Galpha subunits in
      HEK293 cells, CXCL8 production was herein demonstrated to be most effectively
      stimulated by Galphaq family members, while those of Galphas and Galpha12
      elicited much weaker activities, and Galphai being totally ineffective. However,
      in cell lines such as HepG2, HeLa, and MCF-7 that endogenously express Gbetagamma
      responsive phospholipase Cbeta isoforms (PLCbeta2/3), activation of the Gi
      coupled alpha2-adrenoceptor significantly stimulated CXCL8 production. This Gi
      induced CXCL8 production was apparently mediated via specific Gbetagamma dimers
      and required the presence of PLCbeta2/3. Co-activation of Gi-coupled alpha2
      adrenoceptor and Gq-coupled bradykinin receptor resulted in a synergistic CXCL8
      production, with Gbetagamma-responsive PLCbeta2/3, Src, ERK, and STAT3 serving as
      critical signaling intermediates. The treatment of HepG2 and B-10 endothelial
      cells with bradykinin stimulated CXCL8 production and cell proliferation.
      Interestingly, the latter response was driven by CXCL8 autocrine signaling
      because it was abolished by SB225002, an antagonist that prevents CXCL8 from
      binding to CXCR2. Collectively, our results provide a mechanistic basis for
      various G protein subfamilies to regulate the production of CXCL8, which may then
      lead to paracrine and/or autocrine signaling with major implications in both
      normal physiology and pathophysiological conditions.

PMID- 27040398
TI  - Laboratory facility to create reference radon + thoron atmosphere under dynamic
      exposure conditions.
AB  - Radon (222Rn) and thoron (220Rn) levels in the environment are typically subject
      to significant random and systematic variations. Creation in the laboratory of
      reproducible and controlled exposure conditions close to that in the real
      environment can be useful for testing 222Rn and 220Rn detectors and for research.
      In this report the design and performance of a novel laboratory facility with
      such functionality is presented. The facility allows the exposure of detectors
      under controlled dynamic as well as static activity concentrations of 222Rn and
      220Rn (pure and mixed) and temperature. The temperature is measured and regulated
      within -15  degrees C / +60  degrees C by a dedicated programmable thermostat.
      Different reference activity concentrations in the exposure vessel are made by
      regulating the flow-rate of the air that flushes 222Rn/220Rn activity from the
      sources towards the exposure vessel. Reference atmospheres that contain 222Rn,
      220Rn or a specified ratio of the two can be created. Pilot experiments that
      demonstrate the feasibility of the approach are presented. They include follow-up
      of a pre-defined temperature profile (in the range -5  degrees C / +35  degrees
      C), test of the correspondence between planned and measured 222Rn and 220Rn
      activity concentrations, follow-up of a pre-defined dynamic profile of 220Rn
      concentrations and test of the possibility to create mixed 220Rn/222Rn
      atmospheres (experimentally checked for ratio of the activity concentrations from
      0.27 to 4.5). The results from the experimental tests are in agreement with the
      values obtained by the developed theoretical model. The proposed approach can be
      used to plan and create stationary and dynamic reference exposure conditions that
      are close to the real exposure regimes in the environment.

PMID- 27040397
TI  - What Have We Learned from Glycosyltransferase Knockouts in Mice?
AB  - There are five major classes of glycan including N- and O-glycans,
      glycosaminoglycans, glycosphingolipids, and glycophosphatidylinositol anchors,
      all expressed at the molecular frontier of each mammalian cell. Numerous
      biological consequences of altering the expression of mammalian glycans are
      understood at a mechanistic level, but many more remain to be characterized.
      Mouse mutants with deleted, defective, or misexpressed genes that encode
      activities necessary for glycosylation have led the way to identifying key
      functions of glycans in biology. However, with the advent of exome sequencing,
      humans with mutations in genes involved in glycosylation are also revealing
      specific requirements for glycans in mammalian development. The aim of this
      review is to summarize glycosylation genes that are necessary for mouse embryonic
      development, pathway-specific glycosylation genes whose deletion leads to
      postnatal morbidity, and glycosylation genes for which effects are mild, but
      perturbation of the organism may reveal functional consequences. General
      strategies for generating and interpreting the phenotype of mice with
      glycosylation defects are discussed in relation to human congenital disorders of
      glycosylation (CDG).

PMID- 27040399
TI  - Hepatitis B vaccine stored outside the cold chain setting: a pilot study in rural
      Lao PDR.
AB  - BACKGROUND: Hepatitis B vaccine birth dose (HepB-BD) was introduced in Lao
      People's Democratic Republic (Lao-PDR) to prevent perinatal hepatitis B virus
      transmission. HepB-BD, which is labeled for storage between 2 and 8 degrees C, is
      not available at all health facilities, because of some lack of functional cold
      chain; however, previous studies show that HepB-BD is stable if stored outside
      the cold chain (OCC). A pilot study was conducted in Lao-PDR to evaluate impact
      of OCC policy on HepB-BD coverage. METHODS: During the six month pilot, HepB-BD
      was stored OCC for up to 28 days in two intervention districts and stored in cold
      chain in two comparison districts. In the intervention districts, healthcare
      workers were educated about HepB-BD and OCC storage. A post-pilot survey compared
      HepB-BD coverage among children born during the pilot (aged 2-8 months) and
      children born 1 year before (aged 14-20 months). FINDINGS: In the intervention
      districts, 388 children aged 2-8 months and 371 children aged 14-20 months were
      enrolled in the survey; in the comparison districts, 190 children aged 2-8 months
      and 184 children aged 14-20 months were enrolled. Compared with the pre-pilot
      cohort, a 27% median increase in HepB-BD (interquartile range [IQR] 58%,
      p<0.0001) occurred in the pilot cohort in the intervention districts, compared
      with a 0% median change (IQR 25%, p=0.03) in comparison districts. No adverse
      reactions were reported. INTERPRETATION: OCC storage improved HepB-BD coverage
      with no increase in adverse reactions. Findings can guide Lao-PDR on
      implementation and scale-up options of OCC policy.

PMID- 27040400
TI  - Advancing a vaccine to prevent hookworm disease and anemia.
AB  - A human hookworm vaccine is under development and in clinical trials in Africa
      and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It
      elicits neutralizing antibodies that interfere with establishment of the adult
      hookworm in the gut and the ability of the parasite to feed on blood. The vaccine
      target product profile is focused on the immunization of children to prevent
      hookworm infection and anemia caused by Necator americanus. It is intended for
      use in low- and middle-income countries where hookworm is highly endemic and
      responsible for at least three million disability-adjusted life years. So far,
      the human hookworm vaccine is being developed in the non-profit sector through
      the Sabin Vaccine Institute Product Development Partnership (PDP), in
      collaboration with the HOOKVAC consortium of European and African partners. We
      envision the vaccine to be incorporated into health systems as part of an
      elimination strategy for hookworm infection and other neglected tropical
      diseases, and as a means to reduce global poverty and address the Sustainable
      Development Goals.

PMID- 27040401
TI  - Hippo/Yap Signaling in Cardiac Development and Regeneration.
AB  - OPINION STATEMENT: The heart has historically been considered to be a non
      regenerative organ. Recent insights have suggested that cardiomyocytes have a
      small but measurable ability to regenerate. Moreover, recent work has also shown
      that manipulating the expression of specific genetic pathways can improve the
      ability of the heart to repair itself. These new insights set the stage for the
      development of new treatments for heart failure.

PMID- 27040402
TI  - Influence of experimental history on nicotine self-administration in squirrel
      monkeys.
AB  - RATIONALE: Methods for establishing robust long-term self-administration of
      intravenous (i.v.) nicotine, the primary psychoactive agent in tobacco, are not
      well-established in laboratory animals. OBJECTIVE: Here, we examine the use of a
      fading procedure to establish robust and consistent i.v. nicotine self
      administration under second-order schedule conditions in squirrel monkeys.
      METHODS: First, self-administration behavior was developed in two groups of male
      squirrel monkeys using a second-order fixed-interval 5-min schedule with fixed
      ratio 5 units (FI 5-min (FR5: S)). Comparable performances were maintained by
      i.v. cocaine (0.032 mg/kg/injection (inj); group A, n = 3) and the combination of
      food delivery (20-30 % condensed milk) and 0.01 mg/kg/inj i.v. nicotine (group B,
      n = 3). Subsequently, the concentration of condensed milk was gradually reduced
      to zero in the second group and self-administration behavior was maintained by
      i.v. nicotine alone. Next, self-administration of a range of doses of i.v.
      nicotine (0.001-0.032 mg/kg/inj) and, in additional experiments, the minor
      tobacco alkaloid anatabine (0.01-0.18 mg/kg/inj) was studied in both groups.
      RESULTS: Results show that nicotine and anatabine had reinforcing effects in both
      groups. However, optimal doses of nicotine and anatabine maintained significantly
      higher rates of i.v. self-administration behavior in subjects trained with the
      fading procedure than in subjects provided with a history of cocaine-maintained
      responding. CONCLUSION: These results illustrate conditions under which robust
      i.v. nicotine self-administration can be established in squirrel monkeys and the
      influence of prior experimental history in the expression of reinforcing effects
      of nicotine and anatabine.

PMID- 27040403
TI  - Different patterns of change in bone turnover markers during treatment with bone
      modifying agents for breast cancer patients with bone metastases.
AB  - BACKGROUND: Bone-modifying agents are effective for treatment of breast cancer
      patients with bone metastases. Since their action is mediated through suppression
      of the osteoclast function, their efficacy can be determined by monitoring bone
      turnover markers. However, the clinical significance of these markers is yet to
      be compared. METHODS: For this study, 52 breast cancer patients with bone
      metastases treated with zoledronic acid (n = 36) or denosumab (n = 22) were
      enrolled (6 patients were treated sequentially with both agents). Serum tartrate
      resistant acid phosphatase-5b (TRACP-5b), pyridinoline cross-linked
      carboxyterminal telopeptide of type I collagen (1CTP), N-terminal cross-linking
      telopeptides of type I collagen (NTX) and bone-specific alkaline phosphatase
      (BAP) were measured at pretreatment and 1, 3 and 6 months after treatment.
      RESULTS: Serum TRACP-5b (p < 0.0001), NTX (p = 0.0007) and BAP (p = 0.0032)
      decreased significantly after treatment. The baseline median value of TRACP-5b
      (457.5 mU/dL, range 173-1630 mU/dL) decreased to 137 mU/dL (91-795 mU/dL) 1 month
      after treatment. Reduction in serum NTX and BAP was greatest after 3 and 6
      months, respectively. TRACP-5b, NTX and BAP were above normal levels at baseline
      in 62.5, 25 and 35.3 % of patients, respectively, and nearly 80 % of these
      patients attained normal levels during the treatment. CONCLUSIONS: Although bone
      modifying agents reduced the baseline levels of TRACP-5b, NTX and BAP
      significantly, the reduction patterns differed. TRACP-5b appears to affect levels
      most quickly and sensitively, possibly due to its direct link to the number and
      activity of osteoclasts. These findings suggest that the efficacy of TRACP-5b is
      clinically significant when considering which bone-modifying agents to use for
      breast cancer patients with bone metastases.

PMID- 27040404
TI  - Reconstruction of the proximal femur with a modular resection prosthesis.
AB  - BACKGROUND: Various megaprostheses are currently available for reconstruction of
      the proximal femur after tumor resection. This study evaluates the survival and
      complications of a modular megaprosthesis for reconstruction of the proximal
      femur. MATERIALS AND METHODS: We studied the medical files of 109 tumor patients
      (age range 16-86 years) who underwent proximal femoral reconstruction with the
      MRP((r)) megaprosthesis from 2002 to 2011. There were 70 patients with
      metastases, 34 patients with bone sarcomas, and five patients with hematological
      malignancies; 82 were primary and 27 were revision reconstructions. Mean follow
      up was 2.5 years; 31 patients had a minimum five-year follow-up. We evaluated the
      survival and function of the patients, and the survival and complications of the
      megaprostheses. RESULTS: Survival was significantly higher for the patients with
      bone sarcomas compared to those with metastases and hematological malignancies.
      Mean MSTS functional score was similar between patients with bone sarcomas and
      those with hematological malignancies and metastases, and between patients with
      primary and those with revision reconstructions. Overall survival of the MRP((r))
      megaprostheses was 74 % at 5 and 9 years. Fourteen (13.6 %) major complications
      occurred at a mean period of 1.4 years (range 3 months to 4.5 years); these
      included infection (5.8 %), dislocation (3.9 %), local recurrence (2.9 %), and
      acetabular fracture (1 %). CONCLUSION: MRP((r)) megaprostheses are a valuable
      reconstruction option after tumor resection of the proximal femur.

PMID- 27040405
TI  - MR findings of Lynch syndrome-related uterine endometrial carcinoma: a case
      report.
AB  - A 41-year-old woman presented with atypical genital bleeding. Magnetic resonance
      imaging demonstrated a polypoid mass from the lower uterine segment to cervical
      canal, approximately 32 mm in size. Additionally, a thickened sigmoid colon wall
      showing a markedly high signal intensity on diffusion-weighted imaging was
      observed. Barium enema and colonoscopy revealed a type I sigmoid colon cancer.
      Since this patient was relatively young and had multiple relatives with colon
      cancer, Lynch syndrome was suspected and proved by an immunohistochemical survey.
      Uterine endometrial carcinoma related to Lynch syndrome tends to occur in the
      lower uterine segment. Radiologists should be aware of this syndrome so that the
      correct diagnosis can be suggested in the imaging report.

PMID- 27040406
TI  - The triangular cord sign.

PMID- 27040407
TI  - Small (<4 cm) clear cell renal cell carcinoma: correlation between CT findings
      and histologic grade.
AB  - PURPOSE: To evaluate the correlation between CT findings and histologic grade of
      small clear cell renal cell carcinoma (ccRCC). METHODS: CT scans of 101 patients
      with small ccRCC were reviewed independently by two radiologists for tumor size,
      shape, margin, encapsulation, enhancement pattern, and visual relative
      enhancement. Enhancement patterns were defined according to the percentage of
      uniform enhancement [pattern 1, homogeneous (>=90%); pattern 2, relatively
      homogeneous (>=75 and <90%); and pattern 3, heterogeneous (<75%)]. Quantitative
      parameters representing attenuation and degree of enhancement were calculated.
      Histologic grade was classified as low (Fuhrman grade I or II) and high (Fuhrman
      grade III or IV). CT imaging variables were analyzed using univariate and
      multivariate analyses. RESULTS: A total of 63 low-grade and 38 high-grade small
      ccRCCs were assessed. Low-grade tumors differed from high-grade tumors with
      respect to enhancement pattern 1 or 2 (p < 0.001 and p < 0.001), smaller size (p
      = 0.002 and p = 0.001), and lower attenuation on unenhanced scan (p < 0.001 and p
      = 0.008). In multivariate analysis, enhancement pattern 1 or 2 and low
      attenuation (<=30 HU) were identified as independent predictors of low-grade
      ccRCC. Accuracy derived from logistic regression analysis was 79.2% for reader 1
      and 70.3% for reader 2. CONCLUSIONS: CT imaging features including tumor
      attenuation and enhancement pattern can be useful to predict the biologic
      behavior of small ccRCC for adequate treatment strategy.

PMID- 27040408
TI  - Novel mutations in the gene for alpha-subunit of retinal cone cyclic nucleotide
      gated channels in a Japanese patient with congenital achromatopsia.
AB  - PURPOSE: To present the characteristics and pathology of a patient with
      congenital achromatopsia. PATIENT AND METHODS: The patient was a 22-year-old
      Japanese woman who was 8 years old when she first visited our clinic.
      Comprehensive ophthalmic examinations including visual acuity measurements,
      perimetry, optical coherence tomography (OCT), fundus autofluorescence (FAF)
      imaging, electroretinography (ERG), and color vision tests were performed. Her
      genomic DNA was used as the template for the amplification of exons of five
      candidate genes for achromatopsia; CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H, and the
      amplified products were sequenced. A missense mutation, found in the CNGA3, was
      studied both electrophysiologically and biochemically. RESULTS: Her phenotype was
      typical of congenital complete achromatopsia. She was followed for 14 years, and
      her vision and fundus findings were stable. However, the scotopic ERG b-waves at
      age 22 were smaller than those at age 8, and her FAF images showed increased
      autofluorescence in both maculae. Genetic examinations revealed combined
      heterozygous mutations of c.997_998delGA and p.M424V in the CNGA3 gene. The
      homomeric channel consisting of the CNGA3 subunit with the p.M424V mutation had a
      weak cGMP-activated current in patch-clamp recordings. In heterologous expression
      analyses, the expression at the cell surface of the mutant CNGA3 subunit was
      about 28 % of the wild type. CONCLUSIONS: The two novel mutations found in the
      CNGA3 gene, c.997_998delGA and p.M424V, can cause complete achromatopsia. The
      vision of the patient was stationary until the third decade of life although the
      FAF was altered at the age of 22 years.

PMID- 27040409
TI  - Emotion Regulation and Loss of Control Eating in Community-Based Adolescents.
AB  - The current study investigated concurrent and prospective associations between
      emotion-related constructs and loss of control (LOC) eating in adolescents.
      Community-based females (N = 588) completed annual self-report assessments of LOC
      eating, emotional awareness, emotion regulation strategies, and neuroticism from
      ages 16 to 18 years. Linear regressions and a regression-based multiple mediation
      model using bootstrapping were computed to examine the relationships among
      emotion-related constructs and LOC eating frequency. In the concurrent model, age
      18 emotional awareness and emotion regulation strategies were associated with age
      18 LOC eating, F(6, 416) = 12.11, p < 0.001, accounting for 4.5 % of the variance
      after controlling for demographics, body mass index, and neuroticism, F change =
      10.81, p < 0.001. In the prospective model, age 17 emotional awareness predicted
      age 18 LOC eating, F(7, 425) = 11.67, p < 0.001, accounting for 1.7 % of unique
      variance beyond the effects of age 16 LOC eating and age 17 demographics, body
      mass index, and neuroticism, F change = 4.26, p = 0.015. In the multiple
      mediation model, age 18 emotion regulation strategies mediated the association
      between age 17 neuroticism and age 18 LOC eating, indirect effect estimate =
      0.003, 95 % confidence interval = 0.001-0.005, after controlling for age 16 LOC
      eating and age 17 demographics, body mass index, and emotion regulation
      variables. Results suggest that deficient emotion regulation may contribute to
      the onset and maintenance of LOC eating in adolescence (although effects were
      small), and may partially explain the well-established prospective relationship
      between negative emotionality and later LOC eating. Prevention and early
      intervention programs should seek to improve adaptive coping in at-risk
      populations.

PMID- 27040410
TI  - Perfluoroalkyl acids and Time-to-Pregnancy: The issue of "parity-conditioning
      bias".

PMID- 27040411
TI  - Response to letter to the editor regarding "Serum perfluoroalkyl acids and time
      to pregnancy in nulliparous women".

PMID- 27040412
TI  - Corrigendum to 'Effect of hemoglobin adjustment on the precision of mercury
      concentrations in maternal and cord blood' [Environ. Res. 132 (2014) 407-412].

PMID- 27040413
TI  - Pediatric desmoid fibromatosis of the parapharyngeal space: A case report and
      review of literature.
AB  - Desmoid fibromatosis, or aggressive fibromatosis, is a benign but locally
      infiltrative fibroblastic neoplasm arising from fascial or musculoaponeurotic
      tissues. Although lacking metastatic potential, head and neck fibromatosis can
      have significant functional or cosmetic morbidities. 7%-15% of all desmoid tumors
      are seen in the head and neck region, 57% of which occur in the pediatric
      population. The incidence of pediatric desmoid tumor peaks around age 8.
      Treatment of choice is complete surgical resection; however, local recurrence is
      common. We present a case of a 14-month-old male with an 8-cm desmoid tumor in
      the right parapharyngeal space and provide an overview of diagnosis and
      management of pediatric head and neck fibromatosis. This is the largest desmoid
      tumor of the parapharyngeal space in the youngest patient described in the
      literature. 

PMID- 27040414
TI  - Sialendoscopy as a management tool in patients with foreign body impaction of the
      salivary gland.
AB  - PURPOSE: It has been long known that sialendoscopy has both diagnostic and
      therapeutic benefits in the identification and treatment of sialadenitis.
      Sialendoscopy can also be used to triage patients with traumatic injury or
      foreign bodies lodged in the parotid gland. PROCEDURES: We present a case of
      traumatic insertion a fishbone into the parotid gland parenchyma that was
      evaluated with sialendoscopy and successfully managed on the basis of stable
      endoscopy findings that correlated with improving symptomatology. MAIN FINDINGS:
      We find that sialendoscopy presents a useful tool to help guide management.
      CONCLUSIONS: We demonstrate that in an asymptomatic patient, foreign body
      impaction with absence of ductal obstruction on endoscopy can successfully be
      followed with simple observation.

PMID- 27040415
TI  - Adenoid cystic carcinoma of the external ear: a population based study.
AB  - PURPOSE: To determine the incidence of adenoid cystic carcinoma of the external
      ear in the United States, and to evaluate the clinical characteristics and
      survival outcomes associated with the disease. MATERIALS AND METHODS: Data were
      extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 Database
      of the National Cancer Institute. The study cohort included patients diagnosed
      with adenoid cystic carcinoma of the external ear from 1973 to 2012. RESULTS: The
      incidence of adenoid cystic carcinoma of the external ear was 0.004 per 100,000.
      The SEER database identified 66 patients meeting the inclusion criteria. Nodal
      metastasis was noted in 13.1% of patients, while 7.9% had distant metastasis.
      Distant metastasis was associated with worse overall survival (HR 10.18).
      However, nodal metastasis had no impact on overall survival (HR 0.15, p = 0.09).
      Surgery alone was associated with improved overall survival (HR 0.26), compared
      with combination surgery and radiotherapy, while radiotherapy alone was
      associated with worse overall survival (HR 20.12). Increasing age (HR 1.12) and
      black race (HR 6.83) were associated with worse overall survival, while female
      sex (HR 0.26) was associated with improved overall survival. CONCLUSION: ACC of
      the external ear is rare. Distant metastasis is a poor prognostic factor.
      However, nodal metastasis does not appear to impact survival. Advanced age, black
      race, and male sex are also poor prognostic factors. Surgical resection alone is
      associated with better survival than combination surgical resection and
      radiation, or radiotherapy alone.

PMID- 27040416
TI  - Using fixed anatomical landmarks to avoid medial rectus injury: a radiographic
      analysis in patients with and without Graves' disease.
AB  - BACKGROUND: Injury to the medial rectus (MR) is a potentially devastating
      complication of orbital and sinus surgery. Precise knowledge of the MR relative
      to the lamina papyracea (LP) is important during endoscopic surgery for both
      Graves' ophthalmopathy and inflammatory disease. The objective of this study is
      to determine the location of the MR in relation to easily identified and
      frequently encountered intranasal landmarks in patients with and without Graves'
      disease. METHODS: High-resolution computed tomography scans were analyzed in 100
      controls and 63 patients with Graves' disease. The MR position was recorded
      relative to the maxillary sinus ostium (MSO), anterior ethmoid artery (AEA), and
      posterior ethmoid artery (PEA)/horizontal basal lamella (BL). Clinically relevant
      variables recorded at each level included the Keros stage, AEA position, MR
      height, and distance of the MR to orbital floor, skull base, and LP. RESULTS: The
      mean distances between the MR and LP were statistically different for both
      groups. Controls at the MSO, AEA, and PEA/BL were 2.92, 1.69, and 1.06mm; for
      Graves' patients measurements at these sites were 2.12, 1.20, and 0.029mm. When
      comparing the two groups, each of these distances were statistically significant
      (p<0.02). There was no difference in ethmoid cavity width (p>0.05) between
      controls (9.66mm) and Graves' patients (9.70mm). Sex, age, and skull base depth
      were not statistically significant factors. CONCLUSION: This study illustrates
      the position of the MR from the perspective of an endoscopic surgeon utilizing
      fixed intranasal landmarks. Knowledge of the position of MR is critical to safely
      perform decompression surgery and when operating adjacent to the LP during
      endoscopic surgery.

PMID- 27040417
TI  - Assessing the utility of serum C-telopeptide cross-link of type 1 collagen as a
      predictor of bisphosphonate-related osteonecrosis of the jaw: A systematic review
      and meta-analysis.
AB  - BACKGROUND: The authors of this systematic review and meta-analysis assessed the
      utility of serum C-telopeptide cross-link of type 1 collagen (sCTX), a biomarker
      of bone resorption, as a predictor of the development of bisphosphonate-related
      osteonecrosis of the jaw (BRONJ). TYPES OF STUDIES REVIEWED: The authors searched
      for studies involving adult participants, written in English, and published
      through January 20, 2016, using the following electronic databases: the Cochrane
      Library, MEDLINE via PubMed, and Web of Science. They also searched Google
      Scholar and the reference lists of all eligible trials and reviews. They
      identified 16 articles that met their inclusion criteria (9 controlled studies
      and 7 case series). They applied the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses.
      They independently extracted data in duplicate, including the characteristics of
      study participants, risk factors, control groups, and outcomes. They assessed
      risk of bias, and they resolved any disagreements between review authors through
      discussion. RESULTS: A meta-analysis with 9 controlled studies revealed no
      significant difference in mean sCTX values between patients with BRONJ and
      control participants (difference in means, -31.417; 95% confidence interval [CI],
      -91.560 to 28.726; P = .306). A second meta-analysis with 4 studies showed no
      significant difference in risk of having an sCTX value below 150 picograms per
      milliliter for patients with BRONJ compared with control participants (risk
      ratio, 1.892; 95% CI, 0.636-5.626; P = .251). CONCLUSIONS AND PRACTICAL
      IMPLICATIONS: A systematic review of the literature with meta-analysis does not
      support the use of sCTX levels as a predictor of the development of BRONJ.
      Further prospective large sample studies are needed to understand the role of
      sCTX as a predictor for BRONJ.

PMID- 27040418
TI  - Maximal effort cytoreductive surgery for disseminated ovarian cancer in a UK
      setting: challenges and possibilities.
AB  - OBJECTIVE: To assess surgical morbidity and mortality of maximal effort
      cytoreductive surgery for disseminated epithelial ovarian cancer (EOC) in a UK
      tertiary center. METHODS/MATERIALS: A monocentric prospective analysis of
      surgical morbidity and mortality was performed for all consecutive EOC patients
      who underwent extensive cytoreductive surgery between 01/2013 and 12/2014.
      Surgical complexity was assessed by the Mayo clinic surgical complexity score
      (SCS). Only patients with high SCS >=5 were included in the analysis. RESULTS: We
      evaluated 118 stage IIIC/IV patients, with a median age of 63 years (range 19
      91); 47.5 % had ascites and 29 % a pleural effusion. Median duration of surgery
      was 247 min (range 100-540 min). Median surgical complexity score was 10 (range 5
      15) consisting of bowel resection (71 %), stoma formation (13.6 %), diaphragmatic
      stripping/resection (67 %), liver/liver capsule resection (39 %), splenectomy (20
      %), resection stomach/lesser sac (26.3 %), pleurectomy (17 %), coeliac
      trunk/subdiaphragmatic lymphadenectomy (8 %). Total macroscopic tumor clearance
      rate was 89 %. Major surgical complication rate was 18.6 % (n = 22), with a 28
      day and 3-month mortality of 1.7 and 3.4 %, respectively. The anastomotic leak
      rate was 0.8 %; fistula/bowel perforation 3.4 %; thromboembolism 3.4 % and
      reoperation 4.2 %. Median intensive care unit and hospital stay were 1.7 (range 0
      104) and 8 days (range 4-118), respectively. Four patients (3.3 %) failed to
      receive chemotherapy within the first 8 postoperative weeks. CONCLUSIONS: Maximal
      effort cytoreductive surgery for EOC is feasible within a UK setting with
      acceptable morbidity, low intestinal stoma rates and without clinically relevant
      delays to postoperative chemotherapy. Careful patient selection, and coordinated
      multidisciplinary effort appear to be the key for good outcome. Future
      evaluations should include quality of life analyses.

PMID- 27040419
TI  - Traditional Chinese medicine valuably augments therapeutic options in the
      treatment of climacteric syndrome.
AB  - Climacteric syndrome refers to recurring symptoms such as hot flashes, chills,
      headache, irritability and depression. This is usually experienced by menopausal
      women and can be related to a hormonal reorganization in the hypothalamic
      pituitary-gonadal axis. In Traditional Chinese Medicine, originating 1000s of
      years ago, above-mentioned symptoms can be interpreted on the basis of the
      philosophic diagnostic concepts, such as the imbalance of Yin and Yang, the Zang
      Fu and Basic substances (e.g. Qi, Blood and Essence). These concepts postulate
      balance and harmonization as the principle aim of a treatment. In this context,
      it is not astounding that one of the most prominent ancient textbooks dating back
      to 500-200 BC, Huang di Neijing: The Yellow Emperor's Classic of Internal
      Medicine gives already first instructions for diagnosis and therapy of
      climacteric symptoms. For therapy, traditional Chinese medicine comprises five
      treatment principles: Chinese herbal medicine, TuiNa (a Chinese form of manual
      therapy), nutrition, activity (e.g. QiGong) and acupuncture (being the most
      widespread form of treatment used in Europe). This review provides an easy access
      to the concepts of traditional Chinese medicine particularly regarding to
      climacteric syndrome and also focuses on current scientific evidence.

PMID- 27040420
TI  - Knotting on heaven's door: 3D color Doppler ultrasound imaging of a true cord
      knot.

PMID- 27040421
TI  - Ultrasound findings of a fetus with osteogenesis imperfecta type I.

PMID- 27040422
TI  - Inhalant allergy compounding the chronic vaginitis syndrome: characterization of
      sensitization patterns, comorbidities and responses to sublingual immunotherapy.
AB  - OBJECTIVE: To characterize sensitization patterns, diagnoses and comorbidities,
      and to assess the response of lower genital tract symptoms to sublingual
      immunotherapy for airborne allergens in a select population of patients with
      chronic vaginitis. METHODS: Fifty-two patients referred for allergy evaluation
      over a 44 month period were studied. Charts were retrospectively reviewed to
      establish: (1) gynecological diagnoses, (2) allergic-immunological diagnoses, and
      (3) IgE-mediated sensitivity to airborne allergens on presentation. Patients were
      contacted at 9-50 months of treatment to assess response to sublingual
      immunotherapy based on a questionnaire addressing frequency and severity of
      symptoms and use of medication to control symptoms. RESULTS: Recurrent
      vulvovaginal candidiasis was identified in 34 (65 %); vulvar vestibulitis
      syndrome in 12 (23 %); and contact dermatitis in 10 (19 %) patients.
      Comorbidities included: non-reflux gastrointestinal complaints in 11 (21 %),
      gastroesophageal reflux in 5 (9 %), migraines in 9 (17 %), chronic non-migrainous
      headaches in 8 (17 %), and chronic sinusitis in 6 patients (11 %). Asthma was
      diagnosed in 8 patients (15 %). Oral allergy syndrome was present in 6 (11 %).
      Most frequent sensitivities were to: ragweed in 33 (63 %), molds in 26 (50 %),
      dust mites in 23 (44 %), and grass in 12 (23 %) patients. Mono-sensitization was
      demonstrated for ragweed in 7 (13 %), and for molds, dust mites and grass for 3
      (5 %) patients each. Candida sensitization was identified in 15 patients with
      chronic vaginitis (28 %). Eleven patients with recurrent vulvovaginal diagnosis
      (32 %) showed Candida sensitization. Response to immunotherapy was generally
      favorable with pruritus/irritation being more responsive than visceral pain.
      CONCLUSIONS: In a Midwestern referral population, chronic vaginitis compounded by
      inhalant allergy showed: (1) high incidence rate of recurrent vulvo-vaginal
      candidiasis, (2) Candida IgE-mediated sensitization in less than one-third of
      patients with recurrent vulvovaginal candidiasis, (3) comorbid conditions not
      dissimilar to those of other allergic patients, and (4) allergen sensitization
      pattern typical for the Midwest.

PMID- 27040423
TI  - Feasibility and surgical outcomes of conventional and robot-assisted laparoscopy
      for early-stage ovarian cancer: a retrospective, multicenter analysis.
AB  - PURPOSE: We aimed to investigate the safety, adequacy and oncological outcomes of
      laparoscopic surgery (LS) and robot-assisted laparoscopic (RALS) approach for the
      treatment of early-stage ovarian cancer. METHODS: We performed a multicentric,
      retrospective cohort study, enrolling patients affected by early-stage ovarian
      cancer who underwent laparoscopic management for early-stage ovarian cancer
      between 2006 and 2014. Surgical, pathologic and oncologic outcome data were
      analyzed to compare LS and RALS performances for early-stage ovarian cancer
      management. RESULTS: 39 patients underwent laparoscopic staging for presumed
      stage I ovarian cancer: 23 underwent LS and 16 underwent RALS. The mean operative
      time was 281 +/- 81 min (LS 288 +/- 88 min; RALS 270 +/- 72 min; p = 0.49). No
      conversion to laparotomy occurred, and one patient had intraoperative hemorrhage
      requiring blood transfusion. Four patients (10.2 %) experienced postoperative
      complications of grade 3 according to the Clavien-Dindo classification. The
      median hospital stay was 3 days (1-15); the differences were not statistically
      significant between two groups [LS = 4 (1-15); RALS = 3 (1-7); p = 0.43]. During
      a mean follow-up period of 19.4 months, tumor recurrence occurred in 3 patients:
      2 (8.7 %) in the LS group and 1 (6.25 %) in the RALS group. Overall survival and
      disease-free survival for the entire cohort were 97.4 and 92.3 %, respectively.
      CONCLUSIONS: LS and RALS seem to be adequate and feasible for the treatment of
      early-stage ovarian cancer in terms of the surgical outcomes and oncological
      safety. Furthermore, in our experience, perioperative outcomes are comparable
      between LS and RALS making them an acceptable approach in selected patients.

PMID- 27040424
TI  - Risk factors for brachial plexus injury in a large cohort with shoulder dystocia.
AB  - OBJECTIVE: To examine birthweight and other predictors of brachial plexus injury
      (BPI) among births complicated by shoulder dystocia. STUDY DESIGN: A
      retrospective cohort study of term births complicated by shoulder dystocia in
      California between 1997 and 2006. Birthweight at time of delivery was stratified
      into 500-g intervals. Women were further stratified by diabetes status, parity,
      and race/ethnicity. The perinatal outcome of BPI was assessed. RESULTS: This
      study included 62,762 deliveries complicated by shoulder dystocia, of which 3168
      (5 %) resulted in BPI. The association between birthweight and BPI remained
      significant regardless of confounders. Each increasing birthweight interval was
      associated with an increasing risk of BPI compared with 3000-3499-g birthweight.
      Race/ethnicity, diabetes, and parity were also independently associated with BPI.
      CONCLUSION: Increasing birthweight increases the risk of BPI among births with
      shoulder dystocia, independent of advanced maternal age, race, parity,
      gestational diabetes, or operative vaginal delivery.

PMID- 27040425
TI  - Hammer sound elicited tinnitus in car body repair worker cured by stapedial
      tenotomy - A case report.
AB  - Abnormal auditory sensations or tinnitus caused by abnormal middle ear muscle
      contraction are extremely rare and uncomfortable for patients. A 67-year-old man
      who performed paint and body work for cars presented at our hospital with
      complaint of an audible and annoying abnormal sound that was synchronous with the
      striking of his hammer against the metal of the car body during his work. The
      patient reported that the sound was audible of left ear with a split-second delay
      after his hammer struck the metal. Preoperative subjective and objective testing
      failed to reveal any abnormal findings in our case. The patient's symptom was
      successfully cured by selective transection of the stapedius tendon. The
      characteristic nature of tinnitus with a split-second delay after striking the
      metal helped our diagnosis and method of intervention in this case. 

PMID- 27040426
TI  - Transcranial direct current stimulation is not effective in the motor strength
      and gait recovery following motor incomplete spinal cord injury during
      Lokomat((r)) gait training.
AB  - OBJECTIVE/HYPOTHESIS: Transcranial direct current stimulation (tDCS) is a
      potential tool to improve motor recovery in patients with neurological disorders.
      Safety and efficacy of this procedure for lower extremity motor strengthe and
      gait function in motor incomplete spinal cord injury (SCI) have not yet been
      addressed. The aim of this study is to optimize the functional outcome in early
      phases of gait rehabilitation assisted by Lokomat((r)) in motor incomplete SCI
      patients using tDCS as an additional treatment to physical therapy. METHODS: We
      performed in a SCI unit a single-centre randomized, double-blind, sham-controlled
      study to investigate safety and efficacy of anodal tDCS of over leg motor cortex
      in motor incomplete SCI patients. Twenty-four SCI patients received either daily
      sessions of anodal tDCS (n=12) at 2mA for 20min to the vertex (leg motor cortex)
      during twenty days or sham tDCS (n=12). Motor deficit was assessed by the lower
      extremity motor score (LEMS) and for gait function: ten meter walking test
      (10MWT) and Walking Index for SCI (WISCI II) at baseline, after last tDCS session
      (after 4 weeks of stimulation), and after 8 weeks (from baseline) for follow-up.
      RESULTS: No side effects were detected during either tDCS or sham. In both
      groups, there was a significant improvement in LEMS (p<0.03), which did not
      significantly differ when comparing anodal and sham tDCS groups. During follow
      up, in both group 5 of 12 patients could perform gait, without significant
      differences in gait velocity, cadence, step length and WISCI-II between both
      groups. CONCLUSION: Combination twenty sessions of daily tDCS to the leg motor
      cortex and Lokomat((r)) gait training appear to be safe in motor incomplete SCI
      patients. There was an expected improvement in both LEMS and gait scales however,
      did not differ between patients treated with anodal or sham tDCS.

PMID- 27040427
TI  - Glutamatergic and central cholinergic dysfunction in the CA1, CA2 and CA3 fields
      on spatial learning and memory in chronic cerebral ischemia-Induced vascular
      dementia of rats.
AB  - Chronic cerebral ischemia (CCI) is associated with cognitive decline in aging,
      vascular dementia and Alzheimer's disease. Substantial evidence has shown that
      chronic cerebral ischemia may cause cognitive impairment, but the underlying
      neurobiological mechanism is poorly understood so far. In the present study, we
      used a rat model of chronic cerebral ischemia by permanent bilateral common
      carotid artery occlusion (BCCAO) to investigate the alterations of glutamatergic
      and central cholinergic dysfunction, and their causal relationship with the
      cognitive deficits induced by chronic cerebral ischemia. We found that BCCAO rats
      exhibited spatial learning and memory impairments dysfunction 3 month after
      BCCAO. Meanwhile, vGluT levels as well as glutamatergic and central cholinergic
      positive neurons in the hippocampus CA1-3 field significantly decreased. The
      protection of glutamergic and cholinergic neurons or regulating glutamate and
      central cholinergic levels in hippocampal subregion may have beneficial effects
      on cognitive impairments associated with the possible mechanism in CCI-induced
      vascular dementia.

PMID- 27040428
TI  - Genetic analysis of FGF20 variants in Chinese Han patients with essential tremor.
AB  - Essential tremor (ET) is one of the most frequent neurological disorders with
      elusive etiology, typically characterized by postural and kinetic tremors.
      Evidence reveals that genetic components are implicated in the development of ET
      and there are some overlaps between ET and Parkinson's disease in clinical
      features and etiology. Variants in the fibroblast growth factor 20 gene (FGF20)
      have been reported to be associated with the risk of Parkinson's disease. To
      evaluate the association between the FGF20 gene variants and ET susceptibility,
      we conducted genetic analysis of five FGF20 variants (rs1721100, rs1989754,
      rs10089600, rs12720208, and rs17550360) in 200 patients with ET and 426
      ethnically-matched Chinese Han normal controls. Statistical analysis did not
      identify significant differences in genotypic or allelic frequencies of variants
      between ET patients and normal controls (all P>0.05). No related haplotype was
      found to be related to the risk of ET. The findings indicate the FGF20 gene might
      not play a dominating role in the genetic predisposition to ET in Chinese Han
      population.

PMID- 27040439
TI  - Comparison of the nutritional content of products, with and without nutrient
      claims, targeted at children in Brazil.
AB  - Many children's food products highlight positive attributes on their front-of
      package labels in the form of nutrient claims. This cross-sectional study
      investigated all retailed packaged foods (n 5620) in a major Brazilian
      supermarket, in order to identify the availability of products targeted at
      children, and to compare the nutritional content of products with and without
      nutrient claims on labels. Data on energy, carbohydrate, protein, fibre, Na and
      total and SFA content, along with the presence and type of nutrient claims, were
      obtained in-store from labels of all products. Products targeted at children were
      identified, divided into eight food groups and compared for their nutritional
      content per 100 g/ml and the presence of nutrient claims using the Mann-Whitney U
      test (P<0.05). Of the 535 food products targeted at children (9.5 % of all
      products), 270 (50.5 %) displayed nutrient claims on their labels. Children's
      products with nutrient claims had either a similar or worse nutritional content
      than their counterparts without nutrient claims. The major differences among
      groups were found in Group 8 (e.g. sauces and ready meals), in which children's
      products bearing nutrient claims had higher energy, carbohydrate, Na and total
      and SFA content per 100 g/ml than products without nutrient claims (P<0.05). This
      suggests that, to prevent misleading parents who are seeking healthier products
      for their children, the regulation on the use of nutrient claims should be
      revised, so that only products with appropriate nutrient profiles are allowed to
      display them.

PMID- 27040440
TI  - Allostery and Biased Agonism at Class B G Protein-Coupled Receptors.
AB  - Class B G protein-coupled receptors (GPCRs) respond to paracrine or endocrine
      peptide hormones involved in control of bone homeostasis, glucose regulation,
      satiety, and gastro-intestinal function, as well as pain transmission. These
      receptors are targets for existing drugs that treat osteoporosis, hypercalcaemia,
      Paget's disease, type II diabetes, and obesity and are being actively pursued as
      targets for numerous other diseases. Exploitation of class B receptors has been
      limited by difficulties with small molecule drug discovery and development and an
      under appreciation of factors governing optimal therapeutic efficacy. Recently,
      there has been increasing awareness of novel attributes of GPCR function that
      offer new opportunity for drug development. These include the presence of
      allosteric binding sites on the receptor that can be exploited as drug binding
      pockets and the ability of individual drugs to enrich subpopulations of receptor
      conformations to selectively control signaling, a phenomenon termed biased
      agonism. In this review, current knowledge of biased signaling and small molecule
      allostery within class B GPCRs is discussed, highlighting areas that have
      progressed significantly over the past decade, in addition to those that remain
      largely unexplored with respect to these phenomena.

PMID- 27040441
TI  - Risk factors for and expression of immune and inflammatory factors in atopic
      dermatitis in Chinese population: A birth cohort study.
AB  - OBJECTIVE: To explore the risk factors for atopic dermatitis (AD) and disclose
      the relationship between immune inflammatory factors (Immunoglobulin E (IgE),
      interleukin (IL)-4, IL-18) and the prevalence of AD in a Chinese population.
      METHODS: To evaluate the risk factors for infant AD, a total of 921 mother
      newborn pairs were recruited through a questionnaire survey conducted during 2009
      2011. Venous blood was collected from the mothers during birth hospitalization
      and umbilical cord blood was collected during delivery. Thirty-five infants with
      AD paired with their mothers served as the patient group. Thirty-five non-AD
      pairs were selected randomly and were used as the control group. Enzyme-linked
      immunosorbent assay (ELISA) was performed to detect the levels of IgE, IL-4, and
      IL-18. The relationship between the prevalence of AD and the levels of IgE, IL-4,
      and IL-18 was analyzed. The risk factors for allergy were assessed in IgE
      positive cases. RESULTS: Family income, parental history of atopy, age of
      menarche, performing housing renovation before pregnancy, instance of a virus
      infection during pregnancy, and calcium supplementation during pregnancy were
      potential factors determining the incidence rate of infant AD. Compared with the
      control group, the AD patient group showed higher levels of IgE and IL-4 in both
      the maternal serum and umbilical cord blood (P < 0.01). In the cases with AD, IL
      8 was increased only in the maternal serum (P < 0.01). In addition, the allergens
      dust mite, mugwort pollen, and mycete spores were risk factors for the incidence
      of IgE-positive AD. CONCLUSION: IgE and IL-4 levels in the maternal serum and
      umbilical cord blood as well as IL-18 level in the maternal serum are related to
      the occurrence of childhood AD. Potential factors for infant AD include family
      income, parental history of atopy, age of menarche, housing renovation before
      pregnancy, virus infection, and calcium supplementation during pregnancy.

PMID- 27040443
TI  - A novel oxidative stress marker in patients with Alzheimer's disease: dynamic
      thiol-disulphide homeostasis.
AB  - OBJECTIVE: The aim of this study was to evaluate the dynamic thiol-disulphide
      homeostasis as an oxidative stress parameter, using a newly proposed method, in
      patients with Alzheimer's disease. METHODS: In total, 97 participants were
      included in the study. Among them, 51 had been diagnosed with Alzheimer's
      disease, and the remaining 46 were healthy individuals. Total thiol (-SH+-S-S-)
      levels and native thiol (-SH) levels in serum of each participant were measured.
      The amount of dynamic disulphide bonds (-S-S-) and (-S-S-) *100/(-SH), (-S-S-)
      *100/(-SH+-S-S-), and -SH*100/(-SH+-S-S-) ratios were calculated from these
      values. The obtained data were used to compare Alzheimer's disease patients with
      healthy individuals. RESULTS: The average total thiol and native thiol levels of
      patient with Alzheimer's disease in the study were found to be significantly
      lower than those levels of healthy individuals. In addition, in the patient
      group, the -S-S-*100/-S-S+-SH ratio was found to be significantly higher, whereas
      the -SH*100/-S-S+-SH ratio was found to be significantly lower compared with
      healthy individuals. Total thiol and native thiol levels, dynamic disulphide bond
      amount, and -S-S-*100/-SH, -S-S-*100/-S-S+-SH, and -SH*100/-S-S+-SH ratios were
      not found to be correlated with mini mental state examination score or duration
      of disease. CONCLUSION: Recent studies have shown that oxidative stress is the
      one of the molecular changes underlying the pathogenesis of Alzheimer's disease.
      In this study, we have investigated the dynamic thiol-disulphide homeostasis in
      patients with Alzheimer's disease, using a novel method.

PMID- 27040442
TI  - Regulation of Macrophage Recognition through the Interplay of Nanoparticle
      Surface Functionality and Protein Corona.
AB  - Using a family of cationic gold nanoparticles (NPs) with similar size and charge,
      we demonstrate that proper surface engineering can control the nature and
      identity of protein corona in physiological serum conditions. The protein coronas
      were highly dependent on the hydrophobicity and arrangement of chemical motifs on
      NP surface. The NPs were uptaken in macrophages in a corona-dependent manner,
      predominantly through recognition of specific complement proteins in the NP
      corona. Taken together, this study shows that surface functionality can be used
      to tune the protein corona formed on NP surface, dictating the interaction of NPs
      with macrophages.

PMID- 27040444
TI  - Examining Public Health Workers' Perceptions Toward Participating in Disaster
      Recovery After Hurricane Sandy: A Quantitative Assessment.
AB  - OBJECTIVE: We aimed to quantitatively gauge local public health workers'
      perceptions toward disaster recovery role expectations among jurisdictions in New
      Jersey and Maryland affected by Hurricane Sandy. METHODS: An online survey was
      made available in 2014 to all employees in 8 Maryland and New Jersey local health
      departments whose jurisdictions had been impacted by Hurricane Sandy in October
      2012. The survey included perceptions of their actual disaster recovery
      involvement across 3 phases: days to weeks, weeks to months, and months to years.
      The survey also queried about their perceptions about future involvement and
      future available support. RESULTS: Sixty-four percent of the 1047 potential staff
      responded to the survey (n=669). Across the 3 phases, 72% to 74% of the pre
      Hurricane Sandy hires knew their roles in disaster recovery, 73% to 75% indicated
      confidence in their assigned roles (self-efficacy), and 58% to 63% indicated that
      their participation made a difference (response efficacy). Of the respondents who
      did not think it likely that they would be asked to participate in future
      disaster recovery efforts (n=70), 39% indicated a willingness to participate.
      CONCLUSION: The marked gaps identified in local public health workers' awareness
      of, sense of efficacy toward, and willingness to participate in disaster recovery
      efforts after Hurricane Sandy represent a significant infrastructural concern of
      policy and programmatic relevance. (Disaster Med Public Health Preparedness.
      2016;10:371-377).

PMID- 27040446
TI  - Grifola frondosa Glycoprotein GFG-3a Arrests S phase, Alters Proteome, and
      Induces Apoptosis in Human Gastric Cancer Cells.
AB  - GFG-3a is a novel glycoprotein previously purified from the fermented mycelia of
      Grifola frondosa with novel sugar compositions and protein sequencing. The
      present study aims to investigate its effects on the cell cycle, differential
      proteins expression, and apoptosis of human gastric cancer SGC-7901 cells. Our
      findings revealed that GFG-3a induced the cell apoptosis and arrested cell cycle
      at S phase. GFG-3a treatment resulted in the differential expression of 21
      proteins in SGC-7901 cells by upregulating 10 proteins including RBBP4 associated
      with cell cycle arrest and downregulating 11 proteins including RUVBL1, NPM,
      HSP90AB1, and GRP78 involved in apoptosis and stress response. qRT-PCR and
      Western blot analysis also suggested that GFG-3a could increase the expressions
      of Caspase-8/-3, p53, Bax, and Bad while decrease the expressions of Bcl2, Bcl
      xl, PI3K, and Akt1. These results indicated that the stress response, p53
      dependent mitochondrial-mediated, Caspase-8/-3-dependent, and PI3k/Akt pathways
      were involved in the GFG-3a-induced apoptosis process in SGC-7901 cells. These
      findings might provide a basis to prevent or treat human gastric cancer with GFG
      3a and understand the tumor-inhibitory molecular mechanisms of mushroom
      glycoproteins. 

PMID- 27040445
TI  - Multicentre study of neoadjuvant chemotherapy for stage I and II oesophageal
      cancer.
AB  - BACKGROUND: The benefit of neoadjuvant chemotherapy (NCT) for early-stage
      oesophageal cancer is unknown. The aim of this study was to assess whether NCT
      improves the outcome of patients with stage I or II disease. METHODS: Data were
      collected from 30 European centres from 2000 to 2010. Patients who received NCT
      for stage I or II oesophageal cancer were compared with patients who underwent
      primary surgery with regard to postoperative morbidity, mortality, and overall
      and disease-free survival. Propensity score matching was used to adjust for
      differences in baseline characteristics. RESULTS: Of 1173 patients recruited (181
      NCT, 992 primary surgery), 651 (55.5 per cent) had clinical stage I disease and
      522 (44.5 per cent) had stage II disease. Comparisons of the NCT and primary
      surgery groups in the matched population (181 patients in each group) revealed in
      hospital mortality rates of 4.4 and 5.5 per cent respectively (P = 0.660), R0
      resection rates of 91.7 and 86.7 per cent (P = 0.338), 5-year overall survival
      rates of 47.7 and 38.6 per cent (hazard ratio (HR) 0.68, 95 per cent c.i. 0.49 to
      0.93; P = 0.016), and 5-year disease-free survival rates of 44.9 and 36.1 per
      cent (HR 0.68, 0.50 to 0.93; P = 0.017). CONCLUSION: NCT was associated with
      better overall and disease-free survival in patients with stage I or II
      oesophageal cancer, without increasing postoperative morbidity.

PMID- 27040447
TI  - Epidemiology and outcomes of hepatitis C infection in elderly US Veterans.
AB  - The chronic hepatitis C (CHC) cohort in the United States is getting older.
      Elderly patients with CHC may be at a high risk of cirrhosis and hepatocellular
      carcinoma (HCC), but also other nonhepatic comorbidities that negatively impact
      their likelihood of receiving or responding to antiviral treatment. There is
      little information on the clinical epidemiology or outcomes of CHC and its
      treatment in the elderly. We conducted a retrospective cohort study of 1 61 744
      patients with a positive Hepatitis C virus RNA in the Veterans Health
      Administration Hepatitis C Clinical Case Registry to examine the association
      between age subgroups (20-49, 50-64, 65-85 years) and risk of cirrhosis, HCC or
      death using Cox proportional hazards models. We also examined the effect of
      treatment with a sustained viral response (SVR) on these outcomes in each age
      subgroup. The age distribution was 36.8% 20- to 49-year-olds, 57.6% 50- to 64
      year-olds and 5.6% 65- to 85-year-olds (i.e. elderly). Risk of cirrhosis, HCC and
      death was significantly elevated in elderly patients [HR cirrhosis = 1.14 (1.00
      1.29), HR HCC = 2.44 (1.99-2.99); HR death 2.09 (1.98-2.22)] compared with
      younger patients. The incidence of HCC was than 8.4 per 1000 PY in the elderly
      compared with 2.6 per 1000 PY and 5.7 per 1000 PY, among the 20-49 and 50-64 age
      groups, respectively. Elderly patients were significantly less likely to receive
      antiviral treatment (3.8% vs 14.8% and 19.1%, P < 0.0001), but among those who
      received treatment SVR was not different among the age groups (33.5% vs 33.2% and
      32.1%). In an analysis limited to those who received treatment, SVR compared to
      treatment receipt with no SVR was associated with a reduction in risk of
      developing cirrhosis (HR = 0.34; 0.18-0.66) and HCC (HR = 0.60; 0.22-1.61) and
      all-cause mortality risk (HR = 0.52, 0.33-0.82). Elderly patients with CHC are
      more likely to develop HCC than younger patients but have traditionally received
      less antiviral treatment than younger patients. However, receipt of curative
      treatment is associated with a benefit in reducing cirrhosis, HCC and overall
      mortality, irrespective of age.

PMID- 27040448
TI  - Psychological therapies for post-traumatic stress disorder and comorbid substance
      use disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a debilitating mental health
      disorder that may develop after exposure to traumatic events. Substance use
      disorder (SUD) is a behavioural disorder in which the use of one or more
      substances is associated with heightened levels of distress, clinically
      significant impairment of functioning, or both. PTSD and SUD frequently occur
      together. The comorbidity is widely recognised as being difficult to treat and is
      associated with poorer treatment completion and poorer outcomes than for either
      condition alone. Several psychological therapies have been developed to treat the
      comorbidity, however there is no consensus about which therapies are most
      effective. OBJECTIVES: To determine the efficacy of psychological therapies aimed
      at treating traumatic stress symptoms, substance misuse symptoms, or both in
      people with comorbid PTSD and SUD in comparison with control conditions (usual
      care, waiting-list conditions, and no treatment) and other psychological
      therapies. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and
      Neurosis Group's Specialised Register (CCDANCTR) all years to 11 March 2015. This
      register contains relevant randomised controlled trials from the Cochrane Library
      (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to
      date). We also searched the World Health Organization International Clinical
      Trials Registry Platform and ClinicalTrials.gov, contacted experts, searched
      bibliographies of included studies, and performed citation searches of identified
      articles. SELECTION CRITERIA: Randomised controlled trials of individual or group
      psychological therapies delivered to individuals with PTSD and comorbid substance
      use, compared with waiting-list conditions, usual care, or minimal intervention
      or to other psychological therapies. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures expected by Cochrane. MAIN RESULTS: We
      included 14 studies with 1506 participants, of which 13 studies were included in
      the quantitative synthesis. Most studies involved adult populations. Studies were
      conducted in a variety of settings. We performed four comparisons investigating
      the effects of psychological therapies with a trauma-focused component and non
      trauma-focused interventions against treatment as usual/minimal intervention and
      other active psychological therapies. Comparisons were stratified for individual-
      or group-based therapies. All active interventions were based on cognitive
      behavioural therapy. Our main findings were as follows.Individual-based
      psychological therapies with a trauma-focused component plus adjunctive SUD
      intervention was more effective than treatment as usual (TAU)/minimal
      intervention for PTSD severity post-treatment (standardised mean difference (SMD)
      -0.41; 95% confidence interval (CI) -0.72 to -0.10; 4 studies; n = 405; very low
      quality evidence) and at 3 to 4 and 5 to 7 months' follow-up. There was no
      evidence of an effect for level of drug/alcohol use post-treatment (SMD -0.13;
      95% CI -0.41 to 0.15; 3 studies; n = 388; very low-quality evidence), but there
      was a small effect in favour of individual psychological therapy at 5 to 7 months
      (SMD -0.28; 95% CI -0.48 to -0.07; 3 studies; n = 388) when compared against TAU.
      Fewer participants completed trauma-focused therapy than TAU (risk ratio (RR)
      0.78; 95% CI 0.64 to 0.96; 3 studies; n = 316; low-quality evidence).Individual
      based psychological therapy with a trauma-focused component did not perform
      better than psychological therapy for SUD only for PTSD severity (mean difference
      (MD) -3.91; 95% CI -19.16 to 11.34; 1 study; n = 46; low-quality evidence) or
      drug/alcohol use (MD -1.27; 95% CI -5.76 to 3.22; 1 study; n = 46; low-quality
      evidence). Findings were based on one small study. No effects were observed for
      rates of therapy completion (RR 1.00; 95% CI 0.74 to 1.36; 1 study; n = 62; low
      quality evidence).Non-trauma-focused psychological therapies did not perform
      better than TAU/minimal intervention for PTSD severity when delivered on an
      individual (SMD -0.22; 95% CI -0.83 to 0.39; 1 study; n = 44; low-quality
      evidence) or group basis (SMD -0.02; 95% CI -0.19 to 0.16; 4 studies; n = 513;
      low-quality evidence). There were no data on the effects on drug/alcohol use for
      individual therapy. There was no evidence of an effect on the level of
      drug/alcohol use for group-based therapy (SMD -0.03; 95% CI -0.37 to 0.31; 4
      studies; n = 414; very low-quality evidence). A post-hoc analysis for full dose
      of a widely established group therapy called Seeking Safety showed reduced
      drug/alcohol use post-treatment (SMD -0.67; 95% CI -1.14 to -0.19; 2 studies; n =
      111), but not at subsequent follow-ups. Data on the number of participants
      completing therapy were not for individual-based therapy. No effects were
      observed for rates of therapy completion for group-based therapy (RR 1.13; 95% CI
      0.88 to 1.45; 2 studies; n = 217; low-quality evidence).Non-trauma-focused
      psychological therapy did not perform better than psychological therapy for SUD
      only for PTSD severity (SMD -0.26; 95% CI -1.29 to 0.77; 2 studies; n = 128; very
      low-quality evidence) or drug/alcohol use (SMD 0.22; 95% CI -0.13 to 0.57; 2
      studies; n = 128; low-quality evidence). No effects were observed for rates of
      therapy completion (RR 0.91; 95% CI 0.68 to 1.20; 2 studies; n = 128; very low
      quality evidence).Several studies reported on adverse events. There were no
      differences between rates of such events in any comparison. We rated several
      studies as being at 'high' or 'unclear' risk of bias in multiple domains,
      including for detection bias and attrition bias. AUTHORS' CONCLUSIONS: We
      assessed the evidence in this review as mostly low to very low quality. Evidence
      showed that individual trauma-focused psychological therapy delivered alongside
      SUD therapy did better than TAU/minimal intervention in reducing PTSD severity
      post-treatment and at long-term follow-up, but only reduced SUD at long-term
      follow-up. All effects were small, and follow-up periods were generally quite
      short. There was evidence that fewer participants receiving trauma-focused
      therapy completed treatment. There was very little evidence to support use of non
      trauma-focused individual- or group-based integrated therapies. Individuals with
      more severe and complex presentations (e.g. serious mental illness, individuals
      with cognitive impairment, and suicidal individuals) were excluded from most
      studies in this review, and so the findings from this review are not
      generalisable to such individuals. Some studies suffered from significant
      methodological problems and some were underpowered, limiting the conclusions that
      can be drawn. Further research is needed in this area.

PMID- 27040449
TI  - Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and
      lipoprotein metabolism.
AB  - The consequences of angiopoietin-like protein 3 (ANGPTL3) deficiency on
      postprandial lipid and lipoprotein metabolism has not been investigated in
      humans. We studied 7 homozygous (undetectable circulating ANGPTL3 levels) and 31
      heterozygous (50% of circulating ANGPTL3 levels) subjects with familial combined
      hypolipidemia (FHBL2) due to inactivating ANGPTL3 mutations in comparison with 35
      controls. All subjects were evaluated at fasting and during 6 h after a high fat
      meal. Postprandial lipid and lipoprotein changes were quantified by calculating
      the areas under the curve (AUCs) using the 6 h concentration data. Plasma changes
      of beta-hydroxybutyric acid (beta-HBA) were measured as marker of hepatic
      oxidation of fatty acids. Compared with controls, homozygotes showed lower
      incremental AUCs (iAUCs) of total TG (-69%, P < 0.001), TG-rich lipoproteins (
      90%, P < 0.001), apoB-48 (-78%, P = 0.032), and larger absolute increase of FFA
      (128%, P < 00.1). Also, heterozygotes displayed attenuated postprandial lipemia,
      but the difference was significant only for the iAUC of apoB-48 (-28%; P < 0.05).
      During the postprandial period, homozygotes, but not heterozygotes, showed a
      lower increase of beta-HBA. Our findings demonstrate that complete ANGPTL3
      deficiency associates with highly reduced postprandial lipemia probably due to
      faster catabolism of intestinally derived lipoproteins, larger expansion of the
      postprandial FFA pool, and decreased influx of dietary-derived fatty acids into
      the liver. These results add information on mechanisms underlying hypolipidemia
      in FHBL2.

PMID- 27040450
TI  - WAT apoC-I secretion: role in delayed chylomicron clearance in vivo and ex vivo
      in WAT in obese subjects.
AB  - Reduced white adipose tissue (WAT) LPL activity delays plasma clearance of TG
      rich lipoproteins (TRLs). We reported the secretion of apoC-I, an LPL inhibitor,
      from WAT ex vivo in women. Therefore we hypothesized that WAT-secreted apoC-I
      associates with reduced WAT LPL activity and TRL clearance. WAT apoC-I secretion
      averaged 86.9 +/- 31.4 pmol/g/4 h and 74.1 +/- 36.6 pmol/g/4 h in 28 women and 11
      men with BMI >=27 kg/m(2), respectively, with no sex differences. Following the
      ingestion of a (13)C-triolein-labeled high-fat meal, subjects with high WAT apoC
      I secretion (above median) had delayed postprandial plasma clearance of dietary
      TRLs, assessed from plasma (13)C-triolein-labeled TGs and apoB48. They also had
      reduced hydrolysis and storage of synthetic (3)H-triolein-labeled ((3)H)-TRLs in
      WAT ex vivo (i.e., in situ LPL activity). Adjusting for WAT in situ LPL activity
      eliminated group differences in chylomicron clearance; while adjusting for plasma
      apoC-I, (3)H-NEFA uptake by WAT, or body composition did not. apoC-I inhibited in
      situ LPL activity in adipocytes in both a concentration- and time-dependent
      manner. There was no change in postprandial WAT apoC-I secretion. WAT apoC-I
      secretion may inhibit WAT LPL activity and promote delayed chylomicron clearance
      in overweight and obese subjects. We propose that reducing WAT apoC-I secretion
      ameliorates postprandial TRL clearance in humans.

PMID- 27040452
TI  - Evaluating complementary networks of restoration plantings for landscape-scale
      occurrence of temporally dynamic species.
AB  - Multibillion dollar investments in land restoration make it critical that
      conservation goals are achieved cost-effectively. Approaches developed for
      systematic conservation planning offer opportunities to evaluate landscape-scale,
      temporally dynamic biodiversity outcomes from restoration and improve on
      traditional approaches that focus on the most species-rich plantings. We
      investigated whether it is possible to apply a complementarity-based approach to
      evaluate the extent to which an existing network of restoration plantings meets
      representation targets. Using a case study of woodland birds of conservation
      concern in southeastern Australia, we compared complementarity-based selections
      of plantings based on temporally dynamic species occurrences with selections
      based on static species occurrences and selections based on ranking plantings by
      species richness. The dynamic complementarity approach, which incorporated
      species occurrences over 5 years, resulted in higher species occurrences and
      proportion of targets met compared with the static complementarity approach, in
      which species occurrences were taken at a single point in time. For equivalent
      cost, the dynamic complementarity approach also always resulted in higher average
      minimum percent occurrence of species maintained through time and a higher
      proportion of the bird community meeting representation targets compared with the
      species-richness approach. Plantings selected under the complementarity
      approaches represented the full range of planting attributes, whereas those
      selected under the species-richness approach were larger in size. Our results
      suggest that future restoration policy should not attempt to achieve all
      conservation goals within individual plantings, but should instead capitalize on
      restoration opportunities as they arise to achieve collective value of multiple
      plantings across the landscape. Networks of restoration plantings with
      complementary attributes of age, size, vegetation structure, and landscape
      context lead to considerably better outcomes than conventional restoration
      objectives of site-scale species richness and are crucial for allocating
      restoration investment wisely to reach desired conservation goals.

PMID- 27040453
TI  - A mechano- and thermoresponsive luminescent cyclophane.
AB  - The first fluorescent cyclophane with mechano- and thermoresponsive solid-state
      fluorescence characteristics is reported. The new cyclophane comprises two 9,10
      bis(phenylethynyl)anthracene moieties that are bridged by tetraethylene glycol
      spacers. The stimuli-responsiveness is based on molecular assembly changes. 

PMID- 27040454
TI  - Composite grafting with pulp adipofascial advancement flaps for treating non
      replantable fingertip amputations.
AB  - BACKGROUND: Non-replantable fingertip amputation is still a clinical challenge.
      We performed modified composite grafting with pulp adipofascial advancement flap
      for Hirase IIA fingertip amputations. Results from a series of patients are
      presented and achieved better outcome than traditional composite grafting.
      PATIENTS AND METHODS: From September 2012 to April 2014, fourteen patients with
      sixteen digits were included in our study. Mean age of patients was 43.9 years
      (20-71 years). All of our patients underwent this procedure under digital block
      anesthesia. We performed pulp adipofascial advancement flap for better soft
      tissue coverage of bone exposure stump first. The amputated parts were defatted,
      trimming, and reattached as composite graft. Age and gender of patients, injured
      finger, Hirase classification, mechanism of trauma, overall graft survival area,
      two-point discrimination (2PD) (mm) at six-month, length of shortening of digit,
      The average disabilities of the arm, shoulder, and hand (DASH) score and
      subjective self-evaluation questionnaire at 6 month were recorded. RESULTS:
      Average graft survival area was 89% (75-100%). Average length of shortening was
      2.2 mm (1.8-3.5 mm). 2PD at six-month after surgery was 6.3 mm in average (5-8
      mm). Average DASH score at 6 month was 1.45 (0.83-2.5). The self-evaluated
      aesthetic results showed twelve patients (85.7%) were very satisfied, and no
      patient was completely unsatisfied. CONCLUSIONS: In Hirase zone IIA traumatic
      fingertip amputation where replantation is difficult, our modified technique of
      composite grafting with pulp adipofascial advancement flap provided an
      alternative choice with high successful rate, acceptable functional and aesthetic
      outcomes. (c) 2016 Wiley Periodicals, Inc. Microsurgery, 2016. (c) 2015 Wiley
      Periodicals, Inc. Microsurgery 36:651-657, 2016.

PMID- 27040455
TI  - Clearance of stored red blood cells is not increased compared with fresh red
      blood cells in a human endotoxemia model.
AB  - BACKGROUND: It is thought that the clearance of transfused red blood cells (RBCs)
      is related both to the storage time of the transfusion product and to the
      inflammatory status of the recipient. We investigated these effects in a
      randomized, "two-hit," healthy volunteer transfusion model, comparing autologous
      RBCs that were stored for 35 days with those that were stored for 2 days. STUDY
      DESIGN AND METHODS: Healthy male volunteers donated 1 unit of autologous RBCs
      either 2 days (2D) or 35 days (35D) before the study date. The experiment was
      started by infusion of 2 ng/kg lipopolysaccharide ("first hit"). Two hours later,
      the stored RBCs ("second hit") were reinfused, followed by the labeling of RBCs
      with biotin. Clearance of biotin-labeled RBCs (BioRBCs) was measured during the 5
      hour posttransfusion endotoxemia period along with measurements of
      phosphatidylserine (PS) exposure, lactadherin binding, and expression of CD47
      (cluster of differentiation 47; a transmembrane protein encoded by the CD47
      gene). RESULTS: In the 2D stored RBCs group, 1.5% +/- 3.4% of infused BioRBCs
      were cleared from the circulation 5 hours posttransfusion versus 4.8% +/- 4.0% in
      the 35D stored RBCs group (p = 0.1). There were no differences in PS exposure,
      lactadherin binding, or CD47 expression between fresh and stored RBCs or between
      pretransfusion and posttransfusion measurements. CONCLUSION: Our study shows a
      low clearance of RBCs even during endotoxemia. Furthermore, short-term clearance
      of BioRBCs during endotoxemia was not related to storage duration. Consistent
      with these observations, PS exposure, lactadherin binding, and CD47 expression
      did not differ between 2D and 35D stored cells before or after transfusion. We
      conclude that, in the presence of endotoxemia, clearance of 35D stored autologous
      RBCs is not increased compared with 2D stored fresh RBCs.

PMID- 27040451
TI  - Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral
      Regurgitation.
AB  - BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone
      with CABG plus mitral-valve repair in patients with moderate ischemic mitral
      regurgitation, we found no significant difference in the left ventricular end
      systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve
      repair was associated with a reduced prevalence of moderate or severe mitral
      regurgitation, but patients had more adverse events. We now report 2-year
      outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone
      or the combined procedure. Patients were followed for 2 years for clinical and
      echocardiographic outcomes. RESULTS: At 2 years, the mean (+/-SD) LVESVI was
      41.2+/-20.0 ml per square meter of body-surface area in the CABG-alone group and
      43.2+/-20.6 ml per square meter in the combined-procedure group (mean improvement
      over baseline, -14.1 ml per square meter and -14.6 ml per square meter,
      respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in
      the combined-procedure group (hazard ratio in the combined-procedure group, 0.90;
      95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between
      group difference in the rank-based assessment of the LVESVI (including death) at
      2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual
      mitral regurgitation was higher in the CABG-alone group than in the combined
      procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission
      and serious adverse events were similar in the two groups, but neurologic events
      and supraventricular arrhythmias remained more frequent in the combined-procedure
      group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation
      undergoing CABG, the addition of mitral-valve repair did not lead to significant
      differences in left ventricular reverse remodeling at 2 years. Mitral-valve
      repair provided a more durable correction of mitral regurgitation but did not
      significantly improve survival or reduce overall adverse events or readmissions
      and was associated with an early hazard of increased neurologic events and
      supraventricular arrhythmias. (Funded by the National Institutes of Health and
      Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

PMID- 27040456
TI  - A comprehensive strategy for the analysis of acoustic compressibility and optical
      deformability on single cells.
AB  - We realized an integrated microfluidic chip that allows measuring both optical
      deformability and acoustic compressibility on single cells, by optical stretching
      and acoustophoresis experiments respectively. Additionally, we propose a
      measurement protocol that allows evaluating the experimental apparatus parameters
      before performing the cell-characterization experiments, including a non
      destructive method to characterize the optical force distribution inside the
      microchannel. The chip was used to study important cell-mechanics parameters in
      two human breast cancer cell lines, MCF7 and MDA-MB231. Results indicate that MDA
      MB231 has both higher acoustic compressibility and higher optical deformability
      than MCF7, but statistical analysis shows that optical deformability and acoustic
      compressibility are not correlated parameters. This result suggests the
      possibility to use them to analyze the response of different cellular structures.
      We also demonstrate that it is possible to perform both measurements on a single
      cell, and that the order of the two experiments does not affect the retrieved
      values. 

PMID- 27040457
TI  - Justification for conducting neurological clinical trials as part of patient care
      within private practice.
AB  - The aim of this review was to assess the benefits and drawbacks of conducting
      neurological clinical trials and research in private practice for the patients,
      clinician, Practice Manager, sponsors/Clinical Research Organisations (CROs) and
      Clinical Trial Coordinator (CTC) to determine if this is justified for all
      involved. A combination of literature reviews, original research articles and
      books were selected from 2005 to 2015. Provided that the practice has sufficient
      number of active trials to prevent financial loss, support staff, adequate
      facilities and equipment and time, the benefits outweigh the drawbacks. Clinical
      trials provide patients with more thorough monitoring, re-imbursement of trial
      related expenses and the opportunity to try an innovative treatment at no charge
      when other options have failed. For the clinician, clinical trials provide more
      information to ensure better care for their patients and improved treatment
      methods, technical experience and global recognition. Trials collect detailed and
      up-to-date information on the benefits and risks of drugs, improving society's
      confidence in clinical research and pharmaceuticals, allow trial sponsors to
      explore new scientific questions and accelerate innovation. For the CTC, industry
      sponsored clinical trials allow potential entry for a career in clinical research
      giving CTCs the opportunity to become Clinical Research Associates (CRAs), Study
      Start-Up Managers or Drug Safety Associates. 

PMID- 27040459
TI  - Dose Reduction versus Dose-interval Prolongation in Eribulin Mesilate Monotherapy
      in Patients with Metastatic Breast Cancer: A Retrospective Comparative Study.
AB  - It is often necessary to modify the dose or schedule of eribulin mesilate (Eri)
      because of adverse events. Therefore, we retrospectively investigated the optimal
      approach for Eri dose adjustment and/or dosage interval adjustment. Patients who
      received Eri at the institutions affiliated with the Division of Oncology of the
      Aichi Prefectural Society of Hospital Pharmacists between July 2011 and November
      2013 were enrolled in this study. We compared the group that underwent dose
      reduction without changes to their dosage interval (dose reduction group) with
      the group that had a change in their dosage interval (dose-interval prolongation
      group). The primary end-point was time to treatment failure (TTF), and the
      secondary end-points were overall survival (OS), overall response rate (ORR),
      clinical benefit rate (CBR), and adverse events. The TTF and OS of the dose
      reduction group were approximately two times longer than those of the dose
      interval prolongation group. In addition, the dose reduction group had
      significantly improved ORR and CBR, which together indicate an antitumor effect
      (p=0.013 and 0.002, respectively). Although peripheral neuropathy occurred
      significantly more frequently in the patients in the dose reduction group
      (p=0.026), it was grade 1 and controllable in most of the cases. There were no
      differences in the occurrence of other adverse effects between the two groups.
      Therefore, we suggest that dose reduction with maintenance of the dosage interval
      is the preferred treatment approach in cases where Eri dose or schedule
      modification is necessary.

PMID- 27040458
TI  - Standard corneal collagen crosslinking versus transepithelial iontophoresis
      assisted corneal crosslinking, 24 months follow-up: randomized control trial.
AB  - PURPOSE: To compare the results of standard corneal crosslinking (CXL) and
      transepithelial iontophoresis-assisted CXL after 24 months follow-up. MATERIAL
      AND METHODS: Corneal crosslinking (CXL) was performed in a series of 149 eyes of
      119 patients with keratoconus I-II of Amsler classification. Depending on the CXL
      method, patients were divided into two groups: (1) 73 eyes with standard CXL and
      (2) 76 eyes with transepithelial iontophoresis-assisted CXL. Depending on the
      group, epithelium removal or administration of riboflavin solution by
      iontophoresis for 10 min was performed, after which standard surface UVA
      irradiation (370 nm, 3 mW/cm2 ) was performed at a 5-cm distance for 30 min.
      RESULTS: A statistically significant difference in corrected distance visual
      acuity (CDVA) was observed between the two groups, with a better outcome in the
      second group after 6 months (p = 0.037); however, no significant difference was
      found 24 months after treatment (p = 0.829). Stabilization and regression of
      keratometry values were achieved in both groups, but standard CXL was more
      effective. The average demarcation line depth in the standard CXL group was 292
      +/- 14 MUm after 14 days and 172 +/- 16 MUm in the transepithelial iontophoresis
      assisted CXL group. No demarcation line was detected after 1 month and 3 months
      in 45% and 100% of the eyes in the second group respectively. CONCLUSION:
      Transepithelial iontophoresis-assisted collagen crosslinking showed to be less
      effective than standard CXL after 24 months of follow-up, possibly due to a more
      superficial formation of corneal collagen crosslinks, however the stopping of
      disease progression was achieved 24 months after procedure.

PMID- 27040460
TI  - Association of maternal characteristics and behaviours with 4-year-old children's
      dietary patterns.
AB  - This study examined the association of family and maternal characteristics with
      preschool children's dietary patterns. Trained interviewers evaluated subsample
      3422 mothers and children enrolled in the population-based birth cohort
      Generation XXI (Porto, Portugal, 2005-2006). Maternal characteristics and
      behaviours (exercise, smoking habits, diet and child-feeding practices) and
      family characteristics were evaluated. Maternal diet was classified by a dietary
      score, and children's dietary patterns were identified by latent class analysis.
      Odds ratios (OR) and confidence intervals (95% CI) were estimated by multinomial
      regression models. The analysis was based on a framework with four conceptual
      levels: maternal socio-economic position (SEP) at 12 years, maternal socio
      economic and demographic characteristics at child's delivery, family
      characteristics and maternal behaviours at child's 4 years. Three dietary
      patterns were identified in children: high in energy-dense foods (EDF); low in
      foods typically consumed at main meals and intermediate in snacks (Snacking);
      higher in healthy foods; and lower in unhealthy ones (Healthier, reference).
      Lower maternal SEP had an overall effect on children's diet (low vs. high SEP;
      EDF, OR = 1.76, 95% CI: 1.42-2.18; Snacking, OR = 1.73, 95% CI: 1.27-2.35), while
      maternal education was directly associated with it (<=9 vs. >12 schooling years,
      EDF, OR = 2.19, 95% CI: 1.70-2.81; Snacking, OR = 2.22, 95% CI: 1.82-3.55).
      Children whose mothers had worse dietary score were significantly more likely to
      follow unhealthier patterns (first vs. fourth quartile; EDF, OR = 9.94, 95% CI:
      7.35-13.44, P-trend < 0.001; Snacking, OR = 4.21, 95% CI: 2.94-6.05, P-trend <
      0.001). Maternal diet was the key factor associated with children's diet, above
      and beyond socio-economic and demographic characteristics, accounting for one
      third of the determination coefficient of the fully adjusted model. At preschool
      age, interventions should give a particular focus on maternal diet and low SEP
      groups.

PMID- 27040461
TI  - Shin-Guard Dermatitis-Detection and Protection.
AB  - With the popularity of soccer among American youth and the associated use of
      protective shin guards, dermatitis from the guard components has emerged.
      Awareness and protective measures may help prevent irritation and the development
      of contact sensitization from the guards. 

PMID- 27040462
TI  - Optimization of fluorescent 8-heteroaryl-guanine probes for monitoring protein
      mediated duplex -> G-quadruplex exchange.
AB  - In this study, we describe the thermal and optical properties of the thrombin
      binding aptamer (TBA) that has been modified at syn-G-tetrad positions with
      fluorescent 8-heteroaryl-2'-deoxyguanosine derivatives consisting of pyrrolyl
      ((Pyr)dG), furyl ((Fur)dG), thienyl ((Th)dG), benzofuryl ((Bfur)dG), indolyl
      ((Ind)dG) and benzothienyl ((Bth)dG). Insertion of the modified base into the syn
      G5 position of TBA decreases duplex stability, but enhances stability of the
      antiparallel G-quadruplex (GQ) structure produced by TBA in the presence of K(+)
      ion and its molecular target, thrombin. The resulting modified TBA (mTBA)
      oligonucleotides have been employed in duplex -> GQ exchange to monitor thrombin
      binding affinity and rates of GQ formation driven by thrombin binding. Our
      studies demonstrate that 8-heteroaryl-dG bases can be inserted into syn-G-tetrad
      positions of TBA without perturbing thrombin binding affinity and that the 8
      thienyl-dG ((Th)dG) analog is particularly useful as an emissive probe for
      monitoring duplex -> GQ exchange due to its heightened emissive sensitivity to
      change in DNA topology compared to the other 8-heteroaryl-dG analogs. The
      positional impact of a single (Th)dG probe versus multiple (Th)dG incorporation
      at syn-G sites of TBA highlight an advantage for di-substituted mTBA
      oligonucleotides for increased emission intensity and rates of duplex -> GQ
      exchange that can be vital for diagnostics through aptamer detection strategies. 

PMID- 27040464
TI  - In situ electrodeposition of a Cu2O/SnO2 periodical heterostructure film for
      photosensor applications.
AB  - Heterostructure materials with a strictly periodic arrangement in hundreds of
      microns based on tunneling modulation are ideal candidates for micro-nanodevice
      applications. In this paper, we propose a Cu2O/SnO2 periodical heterostructure
      film, which is prepared by electrochemical deposition in a quasi-2D ultra-thin
      liquid layer. The surface morphology and the component of the film were analyzed
      by scanning electron microscopy (SEM), scanning probe microscopy (SPM) and
      transmission electron microscopy (TEM). The influences of frequency and amplitude
      of periodic deposition potential on the morphology and regular distribution of
      the interface were studied. The photoresponsivity of this material was
      researched, and the response behaviors for different illumination conditions were
      recorded carefully. Based on the tunneling modulation mechanism, it exhibits
      reasonable photoresponsivity to UV light. 

PMID- 27040463
TI  - Functional nanoparticles for magnetic resonance imaging.
AB  - Nanoparticle-based magnetic resonance imaging (MRI) contrast agents have received
      much attention over the past decade. By virtue of a high payload of magnetic
      moieties, enhanced accumulation at disease sites, and a large surface area for
      additional modification with targeting ligands, nanoparticle-based contrast
      agents offer promising new platforms to further enhance the high resolution and
      sensitivity of MRI for various biomedical applications. T 2 * superparamagnetic
      iron oxide nanoparticles (SPIONs) first demonstrated superior improvement on MRI
      sensitivity. The prevailing SPION attracted growing interest in the development
      of refined nanoscale versions of MRI contrast agents. Afterwards, T 1 -based
      contrast agents were developed, and became the most studied subject in MRI due to
      the positive contrast they provide that avoids the susceptibility associated with
      MRI signal reduction. Recently, chemical exchange saturation transfer (CEST)
      contrast agents have emerged and rapidly gained popularity. The unique aspect of
      CEST contrast agents is that their contrast can be selectively turned 'on' and
      'off' by radiofrequency saturation. Their performance can be further enhanced by
      incorporating a large number of exchangeable protons into well-defined
      nanostructures. Besides activatable CEST contrast agents, there is growing
      interest in developing nanoparticle-based activatable MRI contrast agents
      responsive to stimuli (pH, enzyme, etc.), which improves sensitivity and
      specificity. In this review, we summarize the recent development of various types
      of nanoparticle-based MRI contrast agents, and have focused our discussions on
      the key advantages of introducing nanoparticles in MRI. WIREs Nanomed
      Nanobiotechnol 2016, 8:814-841. doi: 10.1002/wnan.1400 For further resources
      related to this article, please visit the WIREs website.

PMID- 27040465
TI  - Riser Pattern: Another Determinant of Heart Failure With Preserved Ejection
      Fraction.
AB  - Paradoxical increase in blood pressure (BP) during sleep, exceeding those of
      awake BP, is called the "riser" BP pattern, and known as an abnormal circadian BP
      rhythm, has been reported to be associated with adverse cardiovascular prognoses.
      However, the significance of ambulatory BP in heart failure patients with
      preserved ejection fraction (HFpEF) has never been reported. Here, we tested our
      hypothesis that abnormal circadian BP rhythm is associated with HFpEF. The
      authors enrolled 508 patients with hospitalized HF (age 68+/-13 years; 315 men,
      193 women). There were 232 cases of HFpEF and 276 cases of heart failure with
      reduced ejection fraction (HFrEF). The riser BP pattern was significantly more
      frequent in the HFpEF (28.9%) group compared with the HFrEF group (19.9%). In a
      multivariable logistic regression analysis, the riser BP pattern was associated
      with HFpEF (odds ratio, 1.73; 95% confidence interval, 1.02-2.91; P=.041)
      independent of the other covariates. In conclusion, the riser BP pattern was
      associated with HFpEF.

PMID- 27040466
TI  - Vitamin D immunoregulation through dendritic cells.
AB  - Vitamin D (VD3) has been linked to immunological processes, and its
      supplementation may have a role in treatment or prevention of diseases with
      underlying autoimmune or pro-inflammatory states. As initiators of the immune
      responses, dendritic cells (DC) are a potential target of VD3 to dampen
      autoimmunity and inflammation, but the role of DC in VD3-mediated
      immunomodulation in vivo is not understood. In addition to being targets of VD3,
      DC can provide a local source of bioactive VD3 for regulation of T-cell
      responses. Here we review existing studies that describe the tolerogenic
      potential of VD3 on DC, and discuss them in the context of current understanding
      of DC development and function. We speculate on mechanisms that might account for
      the potent but poorly understood tolerogenic activities of VD3 and the role of DC
      as both targets and sources of this hormone.

PMID- 27040467
TI  - Pleural infection in a New Zealand centre: high incidence in Pacific people and
      RAPID score as a prognostic tool.
AB  - BACKGROUND: Whilst there is an increase in incidence of pleural infection
      worldwide, there is a paucity of New Zealand data. AIMS: This study looked at the
      epidemiology of pleural infection in a single New Zealand institution and
      evaluated the RAPID score as a prognostic tool. METHODS: A retrospective review
      was performed on patients with pleural infection over a 3-year period. Pleural
      infection was defined as having clinical evidence of infection and fulfilling one
      of the following: (i) positive pleural fluid Gram stain or culture, (ii) frank
      pus, (iii) pH <7.2 or (iv) radiological evidence of complex effusion. RESULTS:
      There were 108 patients; 76% were male, and mean age was 54 years. Two thirds of
      patients came from the most deprived areas. The dominant ethnic group was Pacific
      people (42%), which was twice as high as the Pacific population in the area
      (19%), P < 0.0001. After adjusting for deprivation, Pacific people were still
      over-represented, P = 0.0002. There were 14 deaths (13%), and these were
      associated with increasing age (P = 0.001) and urea (P = 0.007) but not ethnicity
      or socioeconomic deprivation. The RAPID score found that those in the high-risk
      (P = 0.026) and moderate-risk (P = 0.036) groups had significantly higher
      mortality compared with the low-risk group. CONCLUSION: The over-representation
      of Pacific people with pleural infection is not fully explained by socioeconomic
      deprivation, highlighting other factors at play, such as genetic susceptibility.
      The RAPID score was of clinical utility in predicting mortality in our
      population.

PMID- 27040468
TI  - Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory
      Bowel Disease (IBD): Role of Brain-Gut Axis.
AB  - BACKGROUND: Stress of different origin is known to alter so called "braingut
      axis" and contributes to a broad array of gastrointestinal disorders including
      inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other
      functional gastrointestinal diseases. The stressful situations and various
      stressors including psychosocial events, heat, hypo- and hyperthermia may worsen
      the course of IBD via unknown mechanism. The aims of this paper were to provide
      an overview of experimental and clinical evidences that stress activates the
      brain-gut axis which results in a mucosal mast cells activation and an increase
      in the production of proinflammatory cytokines and other endocrine and humoral
      mediators. METHODS: Research and online content related to effects of stress on
      lower bowel disorders are reviewed and most important mechanisms are delineated.
      RESULTS: Brain conveys the neural, endocrine and circulatory messages to the gut
      via brain-gut axis reflecting changes in corticotrophin releasing hormone, mast
      cells activity, neurotransmission at the autonomic nerves system and intestinal
      barrier function all affecting the pathogenesis of animal colitis and human IBD.
      Stress triggers the hypothalamus-pituitary axis and the activation of the
      autonomic nervous system, an increase in cortisol levels and proinflammatory
      cytokines such as tumor necrosis factor-alpha, interleukin-8, interleukin-1beta
      and interleukin-6. CONCLUSION: The acute or chronic stress enhances the
      intestinal permeability weakening of the tight junctions and increasing bacterial
      translocation into the intestinal wall. An increased microbial load in the
      colonic tissue, excessive cytokine release and a partially blunted immune
      reactivity in response to stress result in its negative impact on IBD.

PMID- 27040470
TI  - The Role of Gender in Adolescents' Social Networks and Alcohol, Tobacco, and Drug
      Use: A Systematic Review.
AB  - BACKGROUND: Despite previous research indicating an adolescents' alcohol,
      tobacco, and other drug (ATOD) use is dependent upon their sex and the sex
      composition of their social network, few social network studies consider sex
      differences and network sex composition as a determinant of adolescents' ATOD use
      behavior. METHODS: This systematic literature review examining how social network
      analytic studies examine adolescent ATOD use behavior is guided by the following
      research questions: (1) How do studies conceptualize sex and network sex
      composition? (2) What types of network affiliations are employed to characterize
      adolescent networks? (3) What is the methodological quality of included studies?
      After searching several electronic databases (PsycINFO, EBSCO, and Communication
      Abstract) and applying our inclusion/exclusion criteria, 48 studies were included
      in the review. RESULTS: Overall, few studies considered sex composition of
      networks in which adolescents are embedded as a determinant that influences
      adolescent ATOD use. Although included studies all exhibited high methodological
      quality, the majority only used friendship networks to characterize adolescent
      social networks and subsequently failed to capture the influence of other network
      types, such as romantic networks. CONCLUSIONS: School-based prevention programs
      could be strengthened by (1) selecting and targeting peer leaders based on sex,
      and (2) leveraging other types of social networks beyond simply friendships.

PMID- 27040469
TI  - Are School Nurses an Overlooked Resource in Reducing Childhood Obesity? A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Schools are a key setting for childhood obesity interventions, yet
      nurses are not often included in delivering these interventions. The objective of
      this systematic review and meta-analysis was to examine school-based
      interventions involving nurses in a role beyond anthropometric measurement for
      effect on change in body measures. METHODS: We performed a systematic review and
      meta-analysis of these papers. RESULTS: The literature search produced 2412
      articles. Eleven met inclusion criteria for the systematic review (4 randomized
      controlled trail [RCT], 7 quasi-experimental) and 8 for the meta-analysis. None
      have been included in prior meta-analyses. Four studies restricted eligibility to
      overweight and/or obese children; 7 included all children regardless of body
      weight. Random effects meta-analytic models represent data from 6050 (body mass
      index [BMI]), 5863 (BMIz), and 416 (BMI percentile) children, respectively.
      Pooled analyses demonstrated statistically significant decreases in BMI (6
      studies: -0.48 [95% CI -0.84, -0.12]; I(2) =91.2%, Q=68.1), BMIz (5 studies: 
      0.10 [95% CI: -0.15, -0.05]; I(2) =0, Q=2.3), and BMI percentile (3 studies: 
      0.41 [95% CI: -0.60, -0.21]; I(2) =0, Q=2.0). CONCLUSIONS: These findings are
      similar to those of other meta-analyses of school-based interventions and suggest
      that school nurses can play a key role in implementing sustainable, effective
      school-based obesity interventions.

PMID- 27040471
TI  - Teaching Healthy Eating to Elementary School Students: A Scoping Review of
      Nutrition Education Resources.
AB  - BACKGROUND: School-based programs represent an ideal setting to enhance healthy
      eating, as most children attend school regularly and consume at least one meal
      and a number of snacks at school each day. However, current research reports that
      elementary school teachers often display low levels of nutritional knowledge,
      self-efficacy, and skills to effectively deliver nutrition education. METHODS:
      The purpose of this review was to understand the availability and quality of
      resources that are accessible for elementary school teachers to use to support
      curriculum delivery or nutrition education programs. The review included 32
      resources from 4 countries in the final analysis from 1989 to 2014. RESULTS: The
      32 resources exhibited 8 dominant teaching strategies: curriculum approaches;
      cross-curricular approaches; parental involvement; experiential learning
      approaches; contingent reinforcement approaches; literary abstraction approaches;
      games-based approaches; and web-based approaches. The resources were accessible
      to elementary school teachers, with all the resources embedding curriculum
      approaches, and most of the resources embedding parental involvement strategies.
      CONCLUSIONS: Resources were less likely to embed cross-curricular and
      experiential learning approaches, as well as contingent reinforcement approaches,
      despite recent research suggesting that the most effective evidence-based
      strategies for improving healthy eating in elementary school children are cross
      curricular and experiential learning approaches.

PMID- 27040472
TI  - Effect of Physically Active Academic Lessons on Body Mass Index and Physical
      Fitness in Primary School Children.
AB  - BACKGROUND: Preventing overweight and improving physical fitness in primary
      school children is a worldwide challenge, and physically active intervention
      programs usually come with the cost of academic instruction time. This study
      aimed to investigate effects of physically active academic lessons on body mass
      index (BMI) and physical fitness in primary school children. METHODS: Dutch
      children attending second- or third-grade class from 12 primary schools (N = 376;
      8.1 +/- 0.7 years) were randomly assigned to a 22-week intervention program or to
      the control group. In addition to measuring BMI before and after the
      intervention, physical fitness was measured with 5 items of the Eurofit test
      battery, measuring cardiovascular and muscular fitness. RESULTS: Multilevel
      analysis showed a significant interaction effect between condition (intervention
      vs control) and grade (B = -0.47; p < .05). For third-grade children, BMI of the
      intervention group did not change significantly during the intervention period,
      whereas a significant increase was found in the control group. No significant
      main or interaction effects were found for cardiovascular or muscular fitness.
      CONCLUSIONS: The current physically active academic lessons had positive effects
      on BMI in third-grade children, but had no effects on cardiovascular and muscular
      fitness.

PMID- 27040473
TI  - The Effectiveness of A School-Based Nutrition Intervention on Children's Fruit,
      Vegetables, and Dairy Product Intake.
AB  - BACKGROUND: Most Canadian children do not meet daily recommendations for
      consumption of vegetables and fruits (V/F) and dairy products (DP). The aim of
      this study was to evaluate the impact of Team Nutriathlon on V/F and DP
      consumption of children. METHODS: Participants were 404 children from grades 5
      and 6 (intervention group [IG] N = 242, control group [CG] N = 162). Teams of
      children were guided to increase their consumption and variety of V/F and DP over
      an 8-week period. Daily servings of V/F and DP were compared between groups at 4
      time points: baseline (week 0), during (week 6), immediately after (week 9 or
      10), and a follow-up 10 weeks after (week 20) the intervention. RESULTS: During
      and after the program and at follow-up, children in the IG consumed more servings
      of V/F and DP compared to the CG (group * time, p < .0001). Sex, baseline
      consumption levels, and school socioeconomic status did not influence the results
      (p > .05). CONCLUSIONS: Team Nutriathlon is an innovative school-based nutrition
      program that can help to increase the V/F and DP consumption of children.

PMID- 27040475
TI  - Keep Kids in School: A Collaborative Community Effort to Increase Compliance With
      State-Mandated Health Requirements.
AB  - BACKGROUND: It is important that collaborative relationships exist in a community
      to improve access to needed services for children. Such partnerships foster
      preventive services, such as immunizations, and other services that protect the
      health and well-being of all children. METHODS: A collaborative relationship in
      Illinois involving an academic health center, a school district, and county
      health department to address noncompliance with health examination and
      immunization requirements was formed. Parents were additional partners. RESULTS:
      Examinations, screenings, and immunizations increased from previous year
      baselines. Greater fulfillment of health exam mandates resulted in fewer students
      (39% fewer) excluded from admission to school. CONCLUSIONS: The type of
      partnerships described is feasible and can result in improved health care for
      school-aged children who otherwise might be excluded both from health services
      and from school.

PMID- 27040474
TI  - School Start Times, Sleep, Behavioral, Health, and Academic Outcomes: A Review of
      the Literature.
AB  - BACKGROUND: Insufficient sleep in adolescents has been shown to be associated
      with a wide variety of adverse outcomes, from poor mental and physical health to
      behavioral problems and lower academic grades. However, most high school students
      do not get sufficient sleep. Delaying school start times for adolescents has been
      proposed as a policy change to address insufficient sleep in this population and
      potentially to improve students' academic performance, reduce engagement in risk
      behaviors, and improve health. METHODS: This article reviews 38 reports examining
      the association between school start times, sleep, and other outcomes among
      adolescent students. RESULTS: Most studies reviewed provide evidence that
      delaying school start time increases weeknight sleep duration among adolescents,
      primarily by delaying rise times. Most of the studies saw a significant increase
      in sleep duration even with relatively small delays in start times of half an
      hour or so. Later start times also generally correspond to improved attendance,
      less tardiness, less falling asleep in class, better grades, and fewer motor
      vehicle crashes. CONCLUSIONS: Although additional research is necessary, research
      results that are already available should be disseminated to stakeholders to
      enable the development of evidence-based school policies.

PMID- 27040476
TI  - Overcoming Medicaid Reimbursement Barriers to Funding School Nursing Services for
      Low-Income Children With Asthma.
AB  - BACKGROUND: School nurses can provide direct services for children with asthma,
      educate, and reinforce treatment recommendations to children and their families,
      and coordinate the school-wide response to students' asthma emergencies.
      Unfortunately, school-based health services today depend on an unreliable
      patchwork of funding. Limited state and local funds lead to extremely low nurse
      to-student ratios, resulting in missed opportunities for prevention and care of
      asthma and other health conditions. METHODS: We carried out a nonsystematic
      review of legal, government, private health foundation, and medical literature.
      RESULTS: Many health services for asthma and other conditions provided in school
      settings are services typically covered by Medicaid and the Children's Health
      Insurance Program (CHIP) when offered in other settings. However, complex
      reimbursement rules, questionable policy guidance establishing a "free care
      rule," and other barriers have limited the ability of schools to seek
      Medicaid/CHIP reimbursement for these services. Recent legal developments may
      help overcome some of these barriers, and new flexibilities in Medicaid law bring
      opportunities for increased reimbursement of school-based health services.
      CONCLUSIONS: Policymakers should call on the Centers for Medicare and Medicaid
      Services to abandon the "free care rule" and issue other guidance that would
      enable schools to appropriately obtain Medicaid reimbursement for nursing
      services.

PMID- 27040478
TI  - The Journal of Occupational Health from 1959 to 2016.

PMID- 27040477
TI  - Eyes That Thrive in School: A Program to Support Vision Treatment Plans at
      School.

PMID- 27040479
TI  - The global health dimensions of asbestos and asbestos-related diseases.

PMID- 27040480
TI  - Comments on the causation of malignant mesothelioma: rebutting the false concept
      that recent exposures to asbestos do not contribute to causation of mesothelioma.

PMID- 27040481
TI  - Comments on the 2014 helsinki consensus report on asbestos.

PMID- 27040482
TI  - Etiology of Intracranial Arterial Stenosis: Are Transcranial Color-Coded Duplex
      Ultrasound and 3T Black Blood MR Imaging Complementary?
AB  - BACKGROUND: In order to differentiate between the different causes of
      intracranial stenosis, we compared the diagnostic results of transcranial color
      coded duplex (TCCD) sonography with the recently developed 3D high-resolution
      black blood MR sequence. METHODS: We studied retrospectively 20 patients referred
      to our hospital after acute ischemic stroke who were diagnosed with intracranial
      stenosis and in whom a repetitive TCCD and a 3D MR T1 FAT SAT (black blood)
      sequence at 3T (TR/TE 350/20 ms, FOV 160*182*120 mm, 0.4*0.4*0.4 size of pixel,
      300 slices, Fat Sat spair, acquisition time 6 minutes 14) were performed.
      Etiological diagnosis was based on one hand on the morphological aspect of the
      arterial wall (black blood T1 FAT SAT sequence) and on the hemodynamic aspect
      (TCCD) on the other hand. Analysis of black blood T1 FAT SAT MR sequence and TCCD
      agreement on the etiological diagnosis was performed using sign test. RESULTS:
      TCCD was performed at admission and at least at two different intervals during
      follow-up. Eleven patients had diffuse intracranial arterial disease and nine had
      involvement of a single intracranial artery. Etiology of intracranial arterial
      stenosis included: atheromatosis, thrombosis, vasculitis and reversible
      vasoconstriction syndrome. There was 80% agreement (sign test P = .0059) between
      these two methods. CONCLUSIONS: These two combined imaging techniques might be
      promising for the differentiation of arteriosclerotic changes from stenosis of
      another origin, especially when follow-up TCCD studies are completed early before
      a possible regression of the atherosclerotic plaque that might be observed 6
      months after initial diagnosis.

PMID- 27040483
TI  - 3D Imaging of Water-Drop Condensation on Hydrophobic and Hydrophilic Lubricant
      Impregnated Surfaces.
AB  - Condensation of water from the atmosphere on a solid surface is an ubiquitous
      phenomenon in nature and has diverse technological applications, e.g. in heat and
      mass transfer. We investigated the condensation kinetics of water drops on a
      lubricant-impregnated surface, i.e., a micropillar array impregnated with a non
      volatile ionic liquid. Growing and coalescing drops were imaged in 3D using a
      laser scanning confocal microscope equipped with a temperature and humidity
      control. Different stages of condensation can be discriminated. On a lubricant
      impregnated hydrophobic micropillar array these are: (1) Nucleation on the
      lubricant surface. (2) Regular alignment of water drops between micropillars and
      formation of a three-phase contact line on a bottom of the substrate. (3)
      Deformation and bridging by coalescence which eventually leads to a detachment of
      the drops from the bottom substrate. The drop-substrate contact does not result
      in breakdown of the slippery behaviour. Contrary, on a lubricant-impregnated
      hydrophilic micropillar array, the condensed water drops replace the lubricant.
      Consequently, the surface loses its slippery property. Our results demonstrate
      that a Wenzel-like to Cassie transition, required to maintain the facile removal
      of condensed water drops, can be induced by well-chosen surface hydrophobicity. 

PMID- 27040485
TI  - Development: A colourful map of cell fate.

PMID- 27040486
TI  - Gene regulation: Optical control of epigenetics.

PMID- 27040488
TI  - Technique: Transcript tracking by CRISPR.

PMID- 27040487
TI  - Endogenous microRNA sponges: evidence and controversy.
AB  - The competitive endogenous RNA (ceRNA) hypothesis proposes that transcripts with
      shared microRNA (miRNA) binding sites compete for post-transcriptional control.
      This hypothesis has gained substantial attention as a unifying function for long
      non-coding RNAs, pseudogene transcripts and circular RNAs, as well as an
      alternative function for messenger RNAs. Empirical evidence supporting the
      hypothesis is accumulating but not without attracting scepticism. Recent studies
      that model transcriptome-wide binding-site abundance suggest that physiological
      changes in expression of most individual transcripts will not compromise miRNA
      activity. In this Review, we critically evaluate the evidence for and against the
      ceRNA hypothesis to assess the impact of endogenous miRNA-sponge interactions.

PMID- 27040491
TI  - Moral agency and the medical education researcher.

PMID- 27040492
TI  - Experimental Realisation of High-sensitivity Laboratory X-ray Grating-based Phase
      contrast Computed Tomography.
AB  - The possibility to perform high-sensitivity X-ray phase-contrast imaging with
      laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is
      of great interest for a broad range of high-resolution biomedical applications.
      However, achieving high sensitivity with laboratory gbPC-CT setups still poses a
      challenge because several factors such as the reduced flux, the polychromaticity
      of the spectrum, and the limited coherence of the X-ray source reduce the
      performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron
      facilities. In this work, we present our laboratory X-ray Talbot-Lau
      interferometry setup operating at 40 kVp and describe how we achieve the high
      sensitivity yet unrivalled by any other laboratory X-ray phase-contrast
      technique. We provide the angular sensitivity expressed via the minimum
      resolvable refraction angle both in theory and experiment, and compare our data
      with other differential phase-contrast setups. Furthermore, we show that the good
      stability of our high-sensitivity setup allows for tomographic scans, by which
      even the electron density can be retrieved quantitatively as has been
      demonstrated in several preclinical studies.

PMID- 27040493
TI  - Tacky cyclic olefin copolymer: a biocompatible bonding technique for the
      fabrication of microfluidic channels in COC.
AB  - Cyclic olefin copolymer (COC) is widely used in microfluidics due to its UV
      transparency, its biocompatibility and high chemical resistance. Here we present
      a fast and cost-effective solvent bonding technique, which allows for the
      efficient bonding of protein-patterned COC structures. The bonding process is
      carried out at room temperature and takes less than three minutes. Enzyme
      activity is retained upon bonding and microstructure deformation does not occur.

PMID- 27040494
TI  - Iterative protecting group-free cross-coupling leading to chiral multiply
      arylated structures.
AB  - The Suzuki-Miyaura cross-coupling is one of the most often utilized reactions in
      the synthesis of pharmaceutical compounds and conjugated materials. In its most
      common form, the reaction joins two sp(2)-functionalized carbon atoms to make a
      biaryl or diene/polyene unit. These substructures are widely found in natural
      products and small molecules and thus the Suzuki-Miyaura cross-coupling has been
      proposed as the key reaction for the automated assembly of such molecules, using
      protecting group chemistry to affect iterative coupling. We present herein, a
      significant advance in this approach, in which multiply functionalized cross
      coupling partners can be employed in iterative coupling without the use of
      protecting groups. To accomplish this, the orthogonal reactivity of different
      boron substituents towards the boron-to-palladium transmetalation reaction is
      exploited. The approach is illustrated in the preparation of chiral
      enantioenriched compounds, which are known to be privileged structures in active
      pharmaceutical compounds. 

PMID- 27040495
TI  - Innate Lymphocyte/Ly6C(hi) Monocyte Crosstalk Promotes Klebsiella Pneumoniae
      Clearance.
AB  - Increasing antibiotic resistance among bacterial pathogens has rendered some
      infections untreatable with available antibiotics. Klebsiella pneumoniae, a
      bacterial pathogen that has acquired high-level antibiotic resistance, is a
      common cause of pulmonary infections. Optimal clearance of K. pneumoniae from the
      host lung requires TNF and IL-17A. Herein, we demonstrate that inflammatory
      monocytes are rapidly recruited to the lungs of K. pneumoniae-infected mice and
      produce TNF, which markedly increases the frequency of IL-17-producing innate
      lymphoid cells. While pulmonary clearance of K. pneumoniae is preserved in
      neutrophil-depleted mice, monocyte depletion or TNF deficiency impairs IL-17A
      dependent resolution of pneumonia. Monocyte-mediated bacterial uptake and killing
      is enhanced by ILC production of IL-17A, indicating that innate lymphocytes
      engage in a positive-feedback loop with monocytes that promotes clearance of
      pneumonia. Innate immune defense against a highly antibiotic-resistant bacterial
      pathogen depends on crosstalk between inflammatory monocytes and innate
      lymphocytes that is mediated by TNF and IL-17A. 

PMID- 27040497
TI  - Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal
      Translocations.
AB  - Chromosomal translocations encode oncogenic fusion proteins that have been proven
      to be causally involved in tumorigenesis. Our understanding of whether such
      genomic alterations also affect non-coding RNAs is limited, and their impact on
      circular RNAs (circRNAs) has not been explored. Here, we show that well
      established cancer-associated chromosomal translocations give rise to fusion
      circRNAs (f-circRNA) that are produced from transcribed exons of distinct genes
      affected by the translocations. F-circRNAs contribute to cellular transformation,
      promote cell viability and resistance upon therapy, and have tumor-promoting
      properties in in vivo models. Our work expands the current knowledge regarding
      molecular mechanisms involved in cancer onset and progression, with potential
      diagnostic and therapeutic implications.

PMID- 27040496
TI  - A Taste Circuit that Regulates Ingestion by Integrating Food and Hunger Signals.
AB  - Ingestion is a highly regulated behavior that integrates taste and hunger cues to
      balance food intake with metabolic needs. To study the dynamics of ingestion in
      the vinegar fly Drosophila melanogaster, we developed Expresso, an automated
      feeding assay that measures individual meal-bouts with high temporal resolution
      at nanoliter scale. Flies showed discrete, temporally precise ingestion that was
      regulated by hunger state and sucrose concentration. We identify 12 cholinergic
      local interneurons (IN1, for "ingestion neurons") necessary for this behavior.
      Sucrose ingestion caused a rapid and persistent increase in IN1 interneuron
      activity in fasted flies that decreased proportionally in response to subsequent
      feeding bouts. Sucrose responses of IN1 interneurons in fed flies were
      significantly smaller and lacked persistent activity. We propose that IN1 neurons
      monitor ingestion by connecting sugar-sensitive taste neurons in the pharynx to
      neural circuits that control the drive to ingest. Similar mechanisms for
      monitoring and regulating ingestion may exist in vertebrates.

PMID- 27040498
TI  - Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus
      Patients.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss
      of tolerance to nucleic acids and highly diverse clinical manifestations. To
      assess its molecular heterogeneity, we longitudinally profiled the blood
      transcriptome of 158 pediatric patients. Using mixed models accounting for
      repeated measurements, demographics, treatment, disease activity (DA), and
      nephritis class, we confirmed a prevalent IFN signature and identified a
      plasmablast signature as the most robust biomarker of DA. We detected gradual
      enrichment of neutrophil transcripts during progression to active nephritis and
      distinct signatures in response to treatment in different nephritis subclasses.
      Importantly, personalized immunomonitoring uncovered individual correlates of
      disease activity that enabled patient stratification into seven groups, supported
      by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and
      provides an explanation for the failure of clinical trials. This approach may
      improve trial design and implementation of tailored therapies in genetically and
      clinically complex autoimmune diseases. PAPERCLIP. 

PMID- 27040499
TI  - TRIBE: Hijacking an RNA-Editing Enzyme to Identify Cell-Specific Targets of RNA
      Binding Proteins.
AB  - RNA transcripts are bound and regulated by RNA-binding proteins (RBPs). Current
      methods for identifying in vivo targets of an RBP are imperfect and not amenable
      to examining small numbers of cells. To address these issues, we developed TRIBE
      (targets of RNA-binding proteins identified by editing), a technique that couples
      an RBP to the catalytic domain of the Drosophila RNA-editing enzyme ADAR and
      expresses the fusion protein in vivo. RBP targets are marked with novel RNA
      editing events and identified by sequencing RNA. We have used TRIBE to identify
      the targets of three RBPs (Hrp48, dFMR1, and NonA). TRIBE compares favorably to
      other methods, including CLIP, and we have identified RBP targets from as little
      as 150 specific fly neurons. TRIBE can be performed without an antibody and in
      small numbers of specific cells. 

PMID- 27040500
TI  - The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA
      Decay.
AB  - Gene duplication is a major evolutionary force driving adaptation and speciation,
      as it allows for the acquisition of new functions and can augment or diversify
      existing functions. Here, we report a gene duplication event that yielded another
      outcome--the generation of antagonistic functions. One product of this
      duplication event--UPF3B--is critical for the nonsense-mediated RNA decay (NMD)
      pathway, while its autosomal counterpart--UPF3A--encodes an enigmatic protein
      previously shown to have trace NMD activity. Using loss-of-function approaches in
      vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD
      inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A
      acquired repressor activity through simple impairment of a critical domain, a
      rapid mechanism that may have been widely used in evolution. Mice conditionally
      lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and
      gametogenesis. Our results support a model in which UPF3A serves as a molecular
      rheostat that directs developmental events.

PMID- 27040501
TI  - Suppressing molecular vibrations in organic semiconductors by inducing strain.
AB  - Organic molecular semiconductors are solution processable, enabling the growth of
      large-area single-crystal semiconductors. Improving the performance of organic
      semiconductor devices by increasing the charge mobility is an ongoing quest,
      which calls for novel molecular and material design, and improved processing
      conditions. Here we show a method to increase the charge mobility in organic
      single-crystal field-effect transistors, by taking advantage of the inherent
      softness of organic semiconductors. We compress the crystal lattice uniaxially by
      bending the flexible devices, leading to an improved charge transport. The
      mobility increases from 9.7 to 16.5 cm(2) V(-1) s(-1) by 70% under 3% strain. In
      depth analysis indicates that compressing the crystal structure directly
      restricts the vibration of the molecules, thus suppresses dynamic disorder, a
      unique mechanism in organic semiconductors. Since strain can be easily induced
      during the fabrication process, we expect our method to be exploited to build
      high-performance organic devices. 

PMID- 27040502
TI  - Support for nursing science.
AB  - BACKGROUND: The mission of the Department of Health and Human Services is to
      enhance the health and well-being of the American people. It does this by
      providing oversight for more than 1,000 grant programs across 26 federal agencies
      at an annual cost of approximately $500 billion. The National Institute of
      Nursing Research (NINR) at the National Institutes of Health (NIH) is one
      institute originated to support health care research from a nursing perspective.
      However, funding of nursing research from federal agencies has remained
      relatively flat for more than a decade, despite increases in total NIH funding.
      PURPOSE: The purpose of this report is to describe the types of funding support
      provided by federal government agencies (including the NIH) to schools of
      nursing. METHOD: The NIH's Research Portfolio Online Reporting Tool, Expenditures
      and Results system from 1988 to 2014 was accessed to collect information on the
      grant recipient institutions as well as the source, number, type, and dollar
      amounts of grants. DISCUSSION: The funding level and its implications for the
      future of nursing science are considered.

PMID- 27040503
TI  - Effects of n-3 pufas on fasting plasma glucose and insulin resistance in patients
      with impaired fasting glucose or impaired glucose tolerance.
AB  - AIM: to evaluate if a supplementation with n-3 PUFAs at high doses could give a
      regression of the condition of impaired glycemia. METHODS: we enrolled 281
      overweight/obese patients with impaired fasting glucose (IFG) or impaired glucose
      tolerance (IGT); 138 subjects were randomized to n-3 PUFAs group, 1 g three times
      a day, and 143 to placebo for 18 months. We assessed at baseline, and after 9,
      and 18 months: circumferences, body mass index (BMI), fasting plasma glucose
      (FPG), fasting plasma insulin (FPI), HOMA-index, lipid profile. At baseline and
      at the end of the study, all patients underwent an oral glucose tolerance test
      (OGTT). RESULTS: we observed a decrease of glycemia and HOMA-IR with n-3 PUFAs,
      compared to baseline, and to placebo. Fasting plasma insulin decreased with n-3
      PUFAs and increased with placebo. HDL-cholesterol increased after 18 months of n
      3 PUFAs, while triglycerides decreased compared to baseline and to placebo. After
      OGTT performed at the end of the study, more patients returned to a condition of
      euglycemia with n-3 PUFAs compared to placebo. CONCLUSIONS: n-3 PUFAs were
      effective in reducing glycemia in patients affected by IFG or IGT and seem to be
      helpful to slow the development of type 2 diabetes mellitus. (c) 2016 BioFactors,
      42(3):316-322, 2016.

PMID- 27040504
TI  - Nanocomposites of TiO2/cyanoethylated cellulose with ultra high dielectric
      constants.
AB  - A novel dielectric nanocomposite containing a high permittivity polymer,
      cyanoethylated cellulose (CRS) and TiO2 nanoparticles was successfully prepared
      with different weight percentages (10%, 20% and 30%) of TiO2. The intermolecular
      interactions and morphology within the polymer nanocomposites were analysed.
      TiO2/CRS nanofilms on SiO2/Si wafers were used to form metal-insulator-metal type
      capacitors. Capacitances and loss factors in the frequency range of 1 kHz-1 MHz
      were measured. At 1 kHz CRS-TiO2 nanocomposites exhibited ultra high dielectric
      constants of 118, 176 and 207 for nanocomposites with 10%, 20% and 30% weight of
      TiO2 respectively, significantly higher than reported values of pure CRS (21),
      TiO2 (41) and other dielectric polymer-TiO2 nanocomposite films. Furthermore, all
      three CRS-TiO2 nanocomposites show a loss factor <0.3 at 1 kHz and low leakage
      current densities (10(-6)-10(-7) A cm(-2)). Leakage was studied using conductive
      atomic force microscopy and it was observed that the leakage is associated with
      TiO2 nanoparticles embedded in the CRS polymer matrix. A new class of ultra high
      dielectric constant hybrids using nanoscale inorganic dielectrics dispersed in a
      high permittivity polymer suitable for energy management applications is
      reported.

PMID- 27040505
TI  - Evidence for Ethylene-Vinyl-Alcohol-Copolymer Liquid Embolic Agent as a
      Monotherapy in Treatment of Endoleaks.
AB  - OBJECTIVE: Endoleak remains the Achilles heel of endovascular aneurysm repair and
      the exclusion of Type II endoleaks, in particular, remains challenging. This
      systematic review presents the evidence for ethylene-vinyl-alcohol-copolymer
      liquid embolic agent as a monotherapy in the treatment of endoleaks. METHODS: A
      systematic literature search was performed for all studies reporting the use of
      liquid embolic agent as a sole agent in the treatment of endoleaks. Patient
      numbers, clinical details (endoleak type, route of delivery) and outcome in terms
      of survival, technical and clinical success with freedom from endoleak together
      with follow-up period were examined. RESULTS: Only 12 articles reporting the use
      of liquid embolic as the sole treatment modality for endoleaks in 174 patients
      were identified. All but 21 patients had a Type II endoleak. Transarterial
      embolization was attempted in 73% of patients with 48 patients having direct sac
      puncture. Technical success was high at 96%, but in patients with adequate
      imaging, the clinical success rate dropped to 79%. Complications were sparsely
      reported and follow-up ranged from 0 to 75 months. CONCLUSIONS: This review
      highlights the lack of data regarding the use of liquid embolic agent as a
      monotherapy with only 4 studies including more than 10 patients. Data from the
      largest series suggests a learning curve exists and no study reports on cost
      effectiveness. Technical success does not always translate into clinical success
      and with the largest series only reporting median 4-month follow-up no claims
      regarding durability can be made. In problematic Type II endoleaks, however,
      liquid embolic agent is a welcome addition to the treatment armamentarium.

PMID- 27040506
TI  - Unraveling the complexity of mitochondrial complex I assembly: A dynamic process.
AB  - Mammalian complex I is composed of 44 different subunits and its assembly
      requires at least 13 specific assembly factors. Proper function of the
      mitochondrial respiratory chain enzyme is of crucial importance for cell survival
      due to its major participation in energy production and cell signaling. Complex I
      assembly depends on the coordination of several crucial processes that need to be
      tightly interconnected and orchestrated by a number of assembly factors. The
      understanding of complex I assembly evolved from simple sequential concept to the
      more sophisticated modular assembly model describing a convoluted process.
      According to this model, the different modules assemble independently and
      associate afterwards with each other to form the final enzyme. In this review, we
      aim to unravel the complexity of complex I assembly and provide the latest
      insights in this fundamental and fascinating process. This article is part of a
      Special Issue entitled Respiratory complex I, edited by Volker Zickermann and
      Ulrich Brandt. 

PMID- 27040508
TI  - Correction: Drugs in breastfeeding.
AB  - [This corrects the article DOI: 10.18773/austprescr.2015.056.]. 

PMID- 27040507
TI  - Fate of extracellular polymeric substances of anaerobically digested sewage
      sludge during pre-dewatering conditioning with Acidithiobacillus ferrooxidans
      culture.
AB  - This study investigated the fate of extracellular polymeric substances (EPS) of
      anaerobically digested saline sewage sludge during its preconditioning. Sludge
      was conditioned with Acidithiobacillus ferrooxidans (AF) culture for 24h in the
      presence and absence of Fe(2+) as an energy substrate. pH decreased from 7.24 to
      3.12 during sludge conditioning process. The capillary suction time (CST) of
      conditioned sludge significantly decreased to <10s, and specific resistance to
      filtration (SRF) was reduced by >94% as compared with control within 4h of
      conditioning with or without Fe(2+), indicating a significant (P<0.001)
      improvement in sludge dewaterability. A noticeable decrease in extractable EPS
      was observed in conditioned sludge. The EPS contents showed a significant
      negative correlation with dewaterability of sludge (P<0.05). The results suggest
      that bioacidification treatment using A. ferrooxidans effectively improved sludge
      dewaterability through modification of sludge EPS. 

PMID- 27040509
TI  - Lipid partitioning during cardiac stress.
AB  - It is well documented that fatty acids serve as the primary fuel substrate for
      the contracting myocardium. However, extensive research has identified
      significant changes in the myocardial oxidation of fatty acids during acute or
      chronic cardiac stress. As a result, the redistribution or partitioning of fatty
      acids due to metabolic derangements could have biological implications. Fatty
      acids can be stored as triacylglycerols, serve as critical components for
      biosynthesis of phospholipid membranes, and form the potent signaling molecules,
      diacylglycerol and ceramides. Therefore, the contribution of lipid metabolism to
      health and disease is more intricate than a balance of uptake and oxidation. In
      this review, the available data regarding alterations that occur in endogenous
      cardiac lipid pathways during the pathological stressors of ischemia-reperfusion
      and pathological hypertrophy/heart failure are highlighted. In addition, changes
      in endogenous lipids observed in exercise training models are presented for
      comparison. This article is part of a Special Issue entitled: Heart Lipid
      Metabolism edited by G.D. Lopaschuk.

PMID- 27040511
TI  - Achieving quasi-adiabatic thermal environment to maximize resolution power in
      very high-pressure liquid chromatography: Theory, models, and experiments.
AB  - A cylindrical vacuum chamber (inner diameter 5 cm) housing a narrow-bore 2.1
      mm*100 mm column packed with 1.8 MUm HSS-T3 fully porous particles was built in
      order to isolate thermally the chromatographic column from the external air
      environment. Consistent with statistical physics and the mean free path of air
      molecules, the experimental results show that natural air convection and
      conduction are fully eliminated for housing air pressures smaller than 10(-4)
      Torr. Heat radiation is minimized by wrapping up the column with low-emissivity
      aluminum-tape (emissivity coefficient epsilon=0.03 vs. 0.28 for polished
      stainless steel 316). Overall, the heat flux at the column wall is reduced by 96%
      with respect to standard still-air ovens. From a practical viewpoint, the
      efficiency of the column run at a flow rate of 0.6 mL/min at a constant 13,000
      psi pressure drop (the viscous heat power is around 9 W/m) is improved by up to
      35% irrespective of the analyte retention. Models of heat and mass transfer
      reveal that (1) the amplitude of the radial temperature gradient is significantly
      reduced from 0.30 to 0.01 K and (2) the observed improvement in resolution power
      stems from a more uniform distribution of the flow velocity across the column
      diameter. The eddy dispersion term in the van Deemter equation is reduced by
      0.8+/-0.1 reduced plate height unit, a significant gain in column performance.

PMID- 27040510
TI  - Altered cellular redox status, sirtuin abundance and clock gene expression in a
      mouse model of developmentally primed NASH.
AB  - BACKGROUND: We have previously shown that high fat (HF) feeding during pregnancy
      primes the development of non-alcoholic steatohepatits (NASH) in the adult
      offspring. However, the underlying mechanisms are unclear. AIMS: Since the
      endogenous molecular clock can regulate hepatic lipid metabolism, we investigated
      whether exposure to a HF diet during development could alter hepatic clock gene
      expression and contribute to NASH onset in later life. METHODS: Female mice were
      fed either a control (C, 7%kcal fat) or HF (45%kcal fat) diet. Offspring were fed
      either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and
      HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1,
      Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and
      clock-controlled genes involved in lipid metabolism (Rev-Erbalpha, Rev-Erbbeta,
      RORalpha, and Srebp1c) were measured in offspring livers. RESULTS: Offspring fed
      a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet
      developed NASH, coupled with significantly reduced NAD(+)/NADH (p<0.05, HF/HF vs
      C/C), Sirt1 (p<0.001, HF/HF vs C/C), Sirt3 (p<0.01, HF/HF vs C/C), perturbed
      clock gene expression, and elevated expression of genes involved lipid
      metabolism, such as Srebp1c (p<0.05, C/HF and HF/HF vs C/C). CONCLUSION: Our
      results suggest that exposure to excess dietary fat during early and post-natal
      life increases the susceptibility to develop NASH in adulthood, involving altered
      cellular redox status, reduced sirtuin abundance, and desynchronized clock gene
      expression.

PMID- 27040512
TI  - Study of the retention of benzotriazoles, benzothiazoles and benzenesulfonamides
      in mixed-mode solid-phase extraction in environmental samples.
AB  - In the present study, the capabilities of strong cation-exchange and strong anion
      exchange sorbents for solid-phase extraction (SPE) have been evaluated for the
      selective retention of benzotriazoles (BTRs), benzothiazoles (BTs) and
      benzenesulfonamides (BSAs), which are a group of neutral analytes with
      interesting properties such as high polarity and the capability of delocalizing
      electron density. The retention of these analytes has been compared in both
      sorbents for the first time, using a SPE procedure specially designed to promote
      ionic retention of the analytes with the objective of including a washing step
      with an organic solvent to eliminate interferences retained by hydrophobic
      interactions. As a result, ionic interactions between the analytes and both
      sorbents were observed, which allowed the successful introduction of a washing
      step using methanol in the SPE procedure even when most of the analytes were in
      their neutral state under SPE conditions. Consequently, a method was developed
      and further validated for each sorbent using liquid chromatography coupled to
      high-resolution mass spectrometry (LC-HRMS). Apart from the development of an
      improved method, special attention was paid to the discussion of the interactions
      present between the sorbents and each group of analytes to explain how these
      analytes in their neutral state might develop ionic interactions with the
      sorbents. At the end, the use of these sorbents helped to simplify previous
      developed methods where hydrophobic/hydrophilic sorbents were used, obtaining
      enhanced results when evaluated in river water and effluent and influent
      wastewaters. 

PMID- 27040513
TI  - Identification and characterization of in vivo metabolites of asulacrine using
      advanced mass spectrophotometry technique in combination with improved data
      mining strategy.
AB  - Asulacrine (ASL) is a broad-spectrum, antitumor drug whose data are promising for
      the treatment of breast and lung cancers; however, a high incidence of phlebitis
      hampered its further development. Phlebitis is associated with generation of
      reactive species. Asulacrine donates electrons and produces oxidative stress in
      chemical reactions. It was expected that ASL would actively metabolize to
      oxidized products through reactive intermediates and produce more products in
      vivo than reported and thus cause phlebitis. A comprehensive study was planned to
      investigate in vivo metabolism of ASL, using high-resolution mass spectrometry
      LC/IT-TOF MS in positive mode. Metabolites were detected by different software by
      applying annotated detection strategy. The possible metabolites and their product
      ions were simultaneously detected by segmented data acquisition to get accurate
      mass values. Segmented data acquisition improved signal-to-noise (S/N) ratio,
      which was helpful to detect metabolites and their fragments even when present in
      trace amounts. A total of 21 metabolites were detected in gender-based biological
      fluids and characterized by comparing their accurate mass values, fragmentation
      patterns, and relative retention times with that of ASL. Among previously
      reported glucuronosylation metabolites, some oxidation, hydroxylation,
      carboxylation, demethylation, hydrogenation, glutamination, and acetylcysteine
      conjugation were detected for the first time. Twenty metabolites were tentatively
      identified by using the annotated strategy for data acquisition and post-data
      mining. 

PMID- 27040514
TI  - A carbohydrate-binding affinity ligand for the specific enrichment of
      glycoproteins.
AB  - One challenge facing the production of glycoprotein therapeutics is the lack of
      stable and selective affinity ligands for their enrichment. Synthetic affinity
      ligands based on the solid phase multi-component Ugi reaction represent a
      desirable option, particularly those incorporating benzoboroxole and its
      derivatives, which have been shown to enrich glycoproteins under physiological
      conditions. Thus, an Ugi ligand, A21C11I8, comprising 5-amino-2
      hydroxymethylphenylboronic acid was synthesised on aldehyde-functionalised
      SepharoseTM. Immobilised A21C11I8 displayed affinity for the glycosylated
      protein, glucose oxidase (GOx), which bound primarily through its glycan moiety.
      The ligand had a preference for sugar alcohols and the furanose form of the
      monosaccharides tested. Compared with immobilised 3-aminophenylboronic acid and
      Concanavalin A, the Ugi ligand was able to purify GOx from spiked Escherichia
      coli supernatants with retention of its maximum enzymatic activity and protein
      recovery. Glycan profiles of human immunoglobulin G tested on A21C11I8 columns
      suggested that the adsorbent possesses the potential to resolve sialylated and
      neutral glycoforms. The benzoboroxole-functionalised Ugi ligand may find
      application in selective glycoform separation. 

PMID- 27040515
TI  - A single BNP measurement in acute heart failure does not reflect the degree of
      congestion.
AB  - INTRODUCTION: Multiple studies found a significant correlation between B-type
      natriuretic peptide (BNP) level and clinical severity of heart failure (HF). We
      aim to study the ability of a single BNP measurement to predict the degree of
      congestion in acute systolic HF. METHODS: Patients enrolled in the ESCAPE trial
      who were admitted with acute systolic HF were divided into tertiles according to
      baseline BNP level with comparison of the degree of congestion across tertiles
      using clinical signs of congestion as well as objective parameters of overload
      checked by the pulmonary artery catheter. RESULTS: A total of 251 cases (mean
      age, 56 years; 75% males) were included in the study after excluding patients
      with normal (n = 43) or extremely elevated BNP (n = 53) due to the known limited
      significance of BNP in predicting the degree of congestion in the latter 2
      instances. These cases were divided into tertiles as follows: tertile 1, BNP less
      than or equal to 376 pg/mL; tertile 2, BNP 377 to 792 pg/mL; and tertile 3, BNP
      greater than or equal to 793 pg/mL. There were significant differences across the
      BNP tertiles in age (P = .03) and body mass index (P = .003). There were no
      differences between the 3 BNP tertiles with regard to the presence of rales (P =
      .533), jugular venous distension (P = .245), positive hepatojugular reflux (P =
      .224), hepatomegaly (P = .489), ascitis (P = .886), lower extremity edema (P =
      .068), or S3 gallop (P = .512). With regard to hemodynamic markers of congestion
      measured via the pulmonary artery catheter, there were no significant differences
      across the BNP tertiles in the right atrial pressure (P = .148), pulmonary
      capillary wedge pressure (P = .140), pulmonary artery systolic pressure (P =
      .155), pulmonary artery diastolic pressure (P = .246), and pulmonary artery mean
      pressure (P = .607). CONCLUSION: Although longitudinal BNP follow-up may be
      valuable in reflecting the degree of congestion, looking at a single BNP
      measurement alone is not a good marker to predict the level of congestion and
      should not be used as a "stand-alone" test for determining aggressiveness of
      diuresis. Management should be guided by the entirety of physical examination,
      laboratory values, and hemodynamic parameters when available.

PMID- 27040516
TI  - Pelvic Nodular Histiocytic and Mesothelial Hyperplasia in a Patient with
      Endometriosis and Uterine Leiomyoma.

PMID- 27040517
TI  - Analysis of Surgical Pathology Data in the HIRA Database: Emphasis on Current
      Status and Endoscopic Submucosal Dissection Specimens.
AB  - BACKGROUND: In Korea, medical institutions make claims for insurance
      reimbursement to the Health Insurance Review and Assessment Service (HIRA). Thus,
      HIRA databases reflect the general medical services that are provided in Korea.
      We conducted two pathology-related studies using a HIRA national patient sample
      (NPS) data (selection probability, 0.03). First, we evaluated the current status
      of general pathologic examination in Korea. Second, we evaluated pathologic
      issues associated with endoscopic submucosal dissection (ESD). METHODS: The
      sample data used in this study was HIRA-NPS-2013-0094. RESULTS: In the NPS
      dataset, 163,372 pathologic examinations were performed in 103,528 patients
      during the year 2013. Considering sampling weight (33.3), it is estimated that
      5,440,288 (163,372 * 33.3) pathologic examinations were performed. Internal
      medicine and general surgery were the most common departments requesting
      pathologic examinations. The region performing pathologic examinations were
      different according to type of medical institution. In total, 490 patients
      underwent ESD, and 43.4% (213/490) underwent ESD due to gastric carcinoma. The
      results of the ESD led to a change in disease code for 10.5% (29/277) of non
      gastric carcinoma patients. In addition, 21 patients (4.3%) underwent surgery
      following the ESD. The average period between ESD and surgery was 44 days.
      CONCLUSIONS: HIRA sample data provide the nation-wide landscape of specific
      procedure. However, in order to reduce the statistical error, further studies
      using entire HIRA data are needed.

PMID- 27040520
TI  - Massive retropneumoperitoneum due to necrotizing acute pancreatitis.

PMID- 27040521
TI  - A note on the path interval distance.
AB  - The path interval distance accounts for global congruence between locally
      incongruent trees. We show that the path interval distance provides a lower bound
      for the nearest neighbor interchange distance. In contrast to the Robinson-Foulds
      distance, random pairs of trees are unlikely to be maximally distant from one
      another under the path interval distance. These features indicate that the path
      interval distance should play a role in phylogenomics where the comparison of
      trees on a fixed set of taxa is becoming increasingly important.

PMID- 27040522
TI  - Evolution of costly explicit memory and cumulative culture.
AB  - Humans can acquire new information and modify it (cumulative culture) based on
      their learning and memory abilities, especially explicit memory, through the
      processes of encoding, consolidation, storage, and retrieval. Explicit memory is
      categorized into semantic and episodic memories. Animals have semantic memory,
      while episodic memory is unique to humans and essential for innovation and the
      evolution of culture. As both episodic and semantic memory are needed for
      innovation, the evolution of explicit memory influences the evolution of culture.
      However, previous theoretical studies have shown that environmental fluctuations
      influence the evolution of imitation (social learning) and innovation (individual
      learning) and assume that memory is not an evolutionary trait. If individuals can
      store and retrieve acquired information properly, they can modify it and innovate
      new information. Therefore, being able to store and retrieve information is
      essential from the perspective of cultural evolution. However, if both storage
      and retrieval were too costly, forgetting and relearning would have an advantage
      over storing and retrieving acquired information. In this study, using
      mathematical analysis and individual-based simulations, we investigate whether
      cumulative culture can promote the coevolution of costly memory and social and
      individual learning, assuming that cumulative culture improves the fitness of
      each individual. The conclusions are: (1) without cumulative culture, a social
      learning cost is essential for the evolution of storage-retrieval. Costly storage
      retrieval can evolve with individual learning but costly social learning does not
      evolve. When low-cost social learning evolves, the repetition of forgetting and
      learning is favored more than the evolution of costly storage-retrieval, even
      though a cultural trait improves the fitness. (2) When cumulative culture exists
      and improves fitness, storage-retrieval can evolve with social and/or individual
      learning, which is not influenced by the degree of the social learning cost.
      Whether individuals socially learn a low level of culture from observing a high
      or the low level of culture influences the evolution of memory and learning,
      especially individual learning.

PMID- 27040523
TI  - Risk perception and choice of place of birth in women with high risk pregnancies:
      A qualitative study.
AB  - Objective To examine the perception of risk among a group of women with high risk
      pregnancies who were either planning to give birth in hospital, or at home
      despite medical advice to the contrary. The intention was to consider differences
      and similarities between the groups to examine how perception of risk relates to
      choice of place of birth. Design Qualitative study using semi-structured
      interviews. Setting Maternity department in a hospital in South East England.
      Participants Twenty-six women with high risk pregnancies, at least 32 weeks
      pregnant. Half were planning hospital births and half homebirths. Measurements
      and findings Semi-structured interviews to investigate women's understanding and
      assessment of risk. Results were analysed using thematic analysis. Five themes
      emerged: understanding of situation; judgement of risk; reassuring factors;
      impact of risk; and coping with risk. Women from both groups had some
      understanding of the implications of their medical/obstetric conditions. They
      displayed concerns about their babies' wellbeing. Women planning homebirths
      assessed their risks as lower and expressed less concerns than women planning
      hospital births. Women planning hospital births more frequently described
      following professional advice. Key conclusions Risk perception is individual and
      subjective. Women with high risk pregnancies who plan to give birth at home
      perceive risk differently to women who plan hospital births. Implications for
      practice Healthcare professionals working with women with high risk pregnancies
      should be aware of the potential for differences in definitions and perceptions
      of risk within this group. 

PMID- 27040524
TI  - The tensions of uncertainty: Midwives managing risk in and of their practice.
AB  - The tensions of uncertainty: midwives managing risk in and of their practice.
      There has been a fundamental shift in past decades in the way midwifery is
      enacted. The midwifery attributes of skilful practice and conscious alertness
      seem to have been replaced by the concept of risk with its connotations of
      control, surveillance and blame. How midwifery manages practice in this risk
      framework is of concern. Taking a critical realist approach this paper reports on
      a theoretically and empirically derived model of midwifery undertaken with New
      Zealand midwives. The model is a three legged birth stool for the midwife which
      describes how she makes sense of risk in practice. The seat of the stool is being
      with women and the legs are 'being a professional', 'working the system' and
      'working with complexity'. The struts which hold the stool together are 'story
      telling'. Risk theory is reviewed in light of the empirical study and a
      theoretical gap of uncertainty and complexity are identified. 

PMID- 27040525
TI  - Characterization of the duck (Anas platyrhynchos) Rbm24 and Rbm38 genes and their
      expression profiles in myoblast and skeletal muscle tissues.
AB  - RNA-binding motif proteins 24 (Rbm24) and 38 (Rbm38) are known to regulate genes
      expression in a post-transcriptional way. However, it remains unclear about the
      similarities and differences between Rbm24 and Rbm38 in terms of their sequence
      characteristics and expression profiles during myoblast differentiation and
      skeletal muscle development. In this study, we found that the coding domain
      sequences (CDSs) of duck Rbm24 and Rbm38 consisted of 678 and 648 nucleotides,
      respectively. Both of them contain a conserved RNA-recognition motif (RRM).
      Phylogenetic analysis showed that duck Rbm24 and Rbm38 were clustered with other
      Aves, nevertheless, avian Rbm24 was clustered with mammalian and reptilian Rbm24;
      avian Rbm38 was clustered with amphibian and reptilian Rbm38. Real-time PCR
      results exhibited that during embryonic stage, Rbm24 and Rbm38 in leg and breast
      muscle increased to their peak (P<0.01) at same time. During postnatal stage, the
      peak of Rbm24 and Rbm38 in leg were found at W5, while the peak of them in breast
      was found at W6 (P<0.01). Moreover, a relative high value of Rbm24 and Rbm38 in
      leg was found at W1 and W3, respectively. Additionally, both Rbm24 and Rbm38
      expressed at each stage of duck myoblast differentiation, however, Rbm24 shared
      similar expression profiles with MEF2C, and Rbm38 shared similar expression
      profiles with MyoG and MEF2A. Furthermore, hierarchical clustering results were
      consistent with the preceding findings. These results serve as a foundation for
      further investigations about similar and different effects of Rbm24 and Rbm38 on
      myoblast differentiation and skeletal muscle development. 

PMID- 27040526
TI  - Molecular characterization and expression profiles of GATA6 in tongue sole
      (Cynoglossus semilaevis).
AB  - GATA-binding protein 6 (GATA6), a transcription factor of the GATA family, plays
      an important role in gonadal cell proliferation, differentiation, and endoderm
      development. In this study, the full-length coding sequence of tongue sole
      (Cynoglossus semilaevis) GATA6 was identified. The sequence consisted of 1494
      nucleotides encoding a peptide of 497 amino acids, which included two conserved
      zinc finger domains. Phylogenetic, gene structure, and synteny analysis showed
      that C. semilaevis GATA6 was homologous to teleost and tetrapod GATA6. C.
      semilaevis GATA6 mRNA exhibited high expression in heart, intestine, liver,
      kidney, and gonad. Embryonic development expression profiles revealed that GATA6
      is involved in morphogenesis because its expression increased at the blastula
      stage. The in situ hybridization results showed strong GATA6 signals in
      spermatogonia, spermatocytes, and Sertoli cells of the testis. The signals were
      also detected in the oogonia and oocytes of the ovary. The expression of C.
      semilaevis GATA6 was sexually dimorphic, and the methylation pattern in the
      promoter region varied among males, females, and pseudomales. These results
      suggested that GATA6 might influence the gonad development and reproduction of C.
      semilaevis. This study provides the groundwork for further development of
      breeding techniques in C. semilaevis. 

PMID- 27040527
TI  - Molecular characterization of two ferritins of the scallop Argopecten purpuratus
      and gene expressions in association with early development, immune response and
      growth rate.
AB  - Ferritin is involved in several iron homoeostasis processes in molluscs. We
      characterized two ferritin homologues and their expression patterns in
      association with early development, growth rate and immune response in the
      scallop Argopecten purpuratus, a species of economic importance for Chile and
      Peru. Two ferritin subunits (Apfer1 and Apfer2) were cloned. Apfer1 cDNA is a
      792bp clone containing a 516bp open reading frame (ORF) that corresponds to a
      novel ferritin subunit in A. purpuratus. Apfer2 cDNA is a 681bp clone containing
      a 522bp ORF that corresponds to a previously sequenced EST. A putative iron
      responsive element (IRE) was identified in the 5'-untranslated region of both
      genes. The deduced protein sequences of both cDNAs possessed the motifs and
      domains characteristic of functional ferritin subunits. Both genes showed
      differential expression patterns at tissue-specific and early development stage
      levels. Apfer1 expression level increased 40-fold along larval developmental
      stages, decreasing markedly after larval settlement. Apfer1 expression in mantle
      tissue was 2.8-fold higher in fast-growing than in slow-growing scallops. Apfer1
      increased 8-fold in haemocytes 24h post-challenge with the bacterium Vibrio
      splendidus. Apfer2 expression did not differ between fast- and slow-growing
      scallops or in response to bacterial challenge. These results suggest that Apfer1
      and Apfer2 may be involved in iron storage, larval development and shell
      formation. Apfer1 expression may additionally be involved in immune response
      against bacterial infections and also in growth; and thus would be a potential
      marker for immune capacity and for fast growth in A. purpuratus. 

PMID- 27040528
TI  - Toehold enabling stem-loop inspired hemiduplex probe with enhanced sensitivity
      and sequence-specific detection of tumor DNA in serum.
AB  - The sensitivity of structure-switchable electrochemical DNA (E-DNA) sensors is
      generally limited by the irremovable redox labels that are close to or distant
      from the sensing interface. To address this issue, we design a semiduplex probe
      inspired by the stem-loop structure, in which the "nicked loop" domain can serve
      as toehold to mediate a target-responsive strand-displacement reaction. Such a
      reaction can fundamentally eliminate the post-responsive background current that
      arises from the irremovable probe, and thus improve the sensitivity. This novel
      toehold E-DNA (tE-DNA) sensor is able to achieve a detection limit as low as
      0.2pM, which is lower than that of the classic stem-loop structured sensor by two
      orders of magnitude. Moreover, the toehold domain endows the sensor an excellent
      selectivity against a single-base mismatched sequence and high binding kinetics.
      By combining this heterogeneous surface-based dynamic self-assembly design with a
      homogeneous enzyme amplification strategy, the sensitivity can be further
      improved by three orders of magnitude to sub-femtomolar level. Additionally, this
      unique biosensor presents reliable reusability, and is capable of probing low
      abundance of target DNA directly in complex matrices, such as human serum, with
      minimal interference. These advantages make our tE-DNA sensor a promising
      contender in the E-DNA sensor family for clinical diagnostics. 

PMID- 27040529
TI  - Production of Influenza Virus HA1 Harboring Native-Like Epitopes by Pichia
      pastoris.
AB  - The outbreak of the H5N1 highly pathogenic avian influenza which exhibits high
      variation had brought a serious threat to the safety of humanity. To overcome
      this high variation, hemagglutinin-based recombinant subunit vaccine with
      rational design has been considered as a substitute for traditional virion-based
      vaccine development. Here, we expressed HA1 part of the hemagglutinin protein
      using the Pichia pastoris expression system and attained a high yield of about
      120 mg/L through the use of fed-batch scalable fermentation. HA1 protein in the
      culture supernatant was purified using two-step ion-exchange chromatography. The
      resultant HA1 protein was homogeneous in solution in a glycosylated form, as
      confirmed by endoglycosidase H treatment. Sedimentation velocity tests, silver
      staining of protein gels, and immunoblotting were used for verification. The
      native HA1 reacted well with conformational, cross-genotype, neutralizing
      monoclonal antibodies, whereas a loss of binding activity was noted with the
      denatured HA1 form. Moreover, the murine anti-HA1 serum exhibited a virus-capture
      capability in the hemagglutination inhibition assay, which suggests that HA1
      harbors native-like epitopes. In conclusion, soluble HA1 was efficiently
      expressed and purified in this study. The functional glycosylated protein will be
      an alternative for the development of recombinant protein-based influenza
      vaccine. 

PMID- 27040530
TI  - Biomimetic Mineralization of the Alginate/Gelatin/Calcium Oxalate Matrix for
      Immobilization of Pectinase: Influence of Matrix on the Pectinolytic Activity.
AB  - Pectinases catalyze the degradation of pectic substances and are used in several
      processes, mainly in food and textile industries. In this study, a biomimetic
      matrix of alginate/gelatin/calcium oxalate (AGOCa) was synthesized for the in
      situ immobilization via encapsulation of crude pectinase from Aspergillus niger
      ATCC 9642, obtaining an immobilization efficiency of about 61.7 %. To determine
      the performance of AGOCa matrix, this was compared to control matrices of
      alginate/calcium oxalate (AOxal) and alginate/water (ACa). By the evaluation of
      pH and temperature effects on the enzyme activity, it was observed an increase on
      pectinolytic activity for both three tested matrices with an increase on pH and
      temperature. The kinetic parameters for pectinase immobilized in the three
      matrices were determined using citric pectin as substrate. Values of K m of
      0.003, 0.0013, and 0.0022 g mL(-1) and V max of 3.85, 4.32, and 3.17 MUmol min(
      1) g(-1) for AGOCa, AOxal, and ACa matrices were obtained, respectively. After 33
      days of storage, the pectinase immobilized in the three different matrices kept
      its initial activity, but that immobilized in AGOCa presented high stability to
      the storage with a relative activity of about 160 %. The enzyme immobilized in
      AGOCa, AOxal, and ACa could be used in 10, 8, and 7 cycles, respectively, keeping
      40 % of its initial activity. 

PMID- 27040531
TI  - Assemblage of Necrophagous Diptera in Atlantic Insular Environments and Response
      to Different Levels of Human Presence.
AB  - Islands act as natural laboratories for ecological studies to explain bioinvasion
      processes and, in this scenario, necrophagous Diptera have never been used as
      model organisms. This study aimed to (i) describe assemblages of necrophagous
      Diptera (Calliphoridae and Sarcophagidae) in two insular environments of
      different origins and distances from mainland, (ii) investigate the effect of
      anthropogenic impact on the assemblage of carrion flies, (iii) to quantify the
      establishment of invasive species in the two islands, and (iv) to infer about the
      conservation status of the islands based on the ecological parameters. Sampling
      was performed in 2011-2012, in the dry and rainy season. Insects were collected
      by using traps with chicken liver or sardine baits. In each island, environments
      exposed to different degrees of human impact were sampled. Ecological analyses
      were carried out to characterize the assemblages of Calliphoridae and
      Sarcophagidae, with emphasis on the relation between native and invasive species.
      In total, 99,862 adults of 21 species of blow flies and flesh flies were
      collected. Overall abundance in the oceanic island was higher than in the
      continental island, although the richness of species was higher in the latter.
      The type of bait did not influence diversity of species sampled in either island.
      No difference was observed in total richness of both families according to the
      gradient of anthropogenic impact, in both islands. The invasive species Chrysomya
      megacephala (Fabricius) was classified as dominant in all environments,
      irrespective of the anthropogenic impact, which raises concern about the
      conservation status of each island.

PMID- 27040532
TI  - Numerical modeling of the dynamic response of a bioluminescent bacterial
      biosensor.
AB  - Water quality and water management are worldwide issues. The analysis of
      pollutants and in particular, heavy metals, is generally conducted by sensitive
      but expensive physicochemical methods. Other alternative methods of analysis,
      such as microbial biosensors, have been developed for their potential simplicity
      and expected moderate cost. Using a biosensor for a long time generates many
      changes in the growth of the immobilized bacteria and consequently alters the
      robustness of the detection. This work simulated the operation of a biosensor for
      the long-term detection of cadmium and improved our understanding of the
      bioluminescence reaction dynamics of bioreporter bacteria inside an agarose
      matrix. The choice of the numerical tools is justified by the difficulty to
      measure experimentally in every condition the biosensor functioning during a long
      time (several days). The numerical simulation of a biomass profile is made by
      coupling the diffusion equation and the consumption/reaction of the nutrients by
      the bacteria. The numerical results show very good agreement with the
      experimental profiles. The growth model verified that the bacterial growth is
      conditioned by both the diffusion and the consumption of the nutrients. Thus,
      there is a high bacterial density in the first millimeter of the immobilization
      matrix. The growth model has been very useful for the development of the
      bioluminescence model inside the gel and shows that a concentration of oxygen
      greater than or equal to 22 % of saturation is required to maintain a significant
      level of bioluminescence. A continuous feeding of nutrients during the process of
      detection of cadmium leads to a biofilm which reduces the diffusion of nutrients
      and restricts the presence of oxygen from the first layer of the agarose (1 mm)
      and affects the intensity of the bioluminescent reaction. The main advantage of
      this work is to link experimental works with numerical models of growth and
      bioluminescence in order to provide a general purpose model to understand,
      anticipate, or predict the dysfunction of a biosensor using immobilized
      bioluminescent bioreporter in a matrix.

PMID- 27040533
TI  - Erratum to: Toxicity assessment of silver nanoparticles in Persian sturgeon
      (Acipenser persicus) and starry sturgeon (Acipenser stellatus) during early life
      stages.

PMID- 27040534
TI  - The role of the PM2.5-associated metals in pathogenesis of child Mycoplasma
      Pneumoniae infections: a systematic review.
AB  - The peak occurrence of Mycoplasma pneumoniae (M. pneumoniae) infections in
      childhood and haze episodes is concurrent. Together, the prevalence of macrolide
      resistant M. pneumoniae varies among countries might also be related to the
      concentration of ambient fine particulate mass (aerodynamic diameter <=2.5 MUm,
      PM2.5). Numerous cohort studies have identified consistent associations between
      ambient PM2.5 and cardiorespiratory morbidity and mortality. PM2.5 is a carrier
      of the heavy metals. The relationship between PM2.5-associated metals and M.
      pneumoniae infections in childhood has been increasingly drawing public
      attention. First, we reviewed original articles and review papers in Pubmed and
      Web of Science regarding M. pneumoniae and PM2.5-associated metal and analyzed
      the structural basis of PM2.5-associated metal interaction with M. pneumoniae.
      Then, the possible mechanisms of action between them were conjectured. Mechanisms
      of oxidative stress induction and modulation of the host immune system and
      inflammatory responses via Toll-like receptors (TLRs) and/or the nuclear factor
      kappa B (NF-kappaB) pathway are postulated to be the result of PM2.5-associated
      metal complex interaction with M. pneumoniae. In addition, a heavy metal effect
      on M. pneumoniae-expressed community-acquired respiratory distress syndrome
      (CARDS) toxin, and activation of the aryl hydrocarbon receptor (AhR) and TLRs to
      induce the differentiation of T helper (Th) cells are also regarded as important
      reasons for the influence of the heavy metals on the severity of M. pneumoniae
      pneumonia and the initial onset and exacerbation of M. pneumoniae associated
      asthma. PM2.5-associated metals via complex mechanisms can exert a great impact
      on the host through interaction with M. pneumoniae. 

PMID- 27040535
TI  - Children exposure to indoor ultrafine particles in urban and rural school
      environments.
AB  - Extended exposure to ultrafine particles (UFPs) may lead to consequences in
      children due to their increased susceptibility when compared to older
      individuals. Since children spend in average 8 h/day in primary schools,
      assessing the number concentrations of UFPs in these institutions is important in
      order to evaluate the health risk for children in primary schools caused by
      indoor air pollution. Thus, the purpose of this study was to assess and determine
      the sources of indoor UFP number concentrations in urban and rural Portuguese
      primary schools. Indoor and outdoor ultrafine particle (UFP) number
      concentrations were measured in six urban schools (US) and two rural schools (RS)
      located in the north of Portugal, during the heating season. The mean number
      concentrations of indoor UFPs were significantly higher in urban schools than in
      rural ones (10.4 * 10(3) and 5.7 * 10(3) pt/cm(3), respectively). Higher UFP
      levels were associated with higher squared meters per student, floor levels
      closer to the ground, chalk boards, furniture or floor covering materials made of
      wood and windows with double-glazing. Indoor number concentrations of ultrafine
      particles were inversely correlated with indoor CO2 levels. In the present work,
      indoor and outdoor concentrations of UFPs in public primary schools located in
      urban and rural areas were assessed, and the main sources were identified for
      each environment. The results not only showed that UFP pollution is present in
      augmented concentrations in US when compared to RS but also revealed some
      classroom/school characteristics that influence the concentrations of UFPs in
      primary schools. 

PMID- 27040536
TI  - Response of bacterial community compositions to different sources of pollutants
      in sediments of a tributary of Taihu Lake, China.
AB  - Sediment bacterial communities are sensitive to water conditions in river
      ecosystems. The objective of this study was to compare the influences of
      different pollution sources, including urban areas, wastewater treatment plants
      (WWTPs), suburban areas, and agricultural areas, on sediment bacterial
      communities along a typical tributary of Taihu Lake, China. The dominant
      composition of the sediment bacterial community was determined using a
      combination of terminal restriction fragment length polymorphism (T-RFLP) and a
      16S rRNA clone library. The results showed that the sediment bacterial
      communities were distinctly affected by the four pollution sources.
      Alphaproteobacteria, Betaproteobacteria, and Actinobacteria (>50 % in total) were
      the predominant bacterial taxa across the sediment samples. Apart from those, the
      sediment bacterial community composition (BCC) affected by WWTP effluent was
      subsequently dominated by Nitrospira (12.4 %) and Bacteroidetes (11.5 %),
      agriculture was dominated by Firmicutes (13.2 %) and Deltaproteobacteria (7.2 %),
      while urban and suburban were dominated by Bacteroidetes (7.6 and 7.9 %,
      respectively) and Deltaproteobacteria (7.9 and 7.6 %, respectively). Cluster
      analysis indicated that the BCC affected by WWTP effluent was distinct from the
      BCC in urban, suburban, and agricultural areas. In addition, the bacterial
      community richness and evenness affected by WWTP effluent were much less than
      those by the other pollution sources. Redundancy analysis (RDA) indicated that
      the variation in BCC across the sediment samples was significantly associated
      with ammonium (17 %), organic matter (12 %), and cadmium (3 %) (p < 0.01).
      Overall, the results indicated that the four different pollution sources (WWTP,
      urban, suburban, and agriculture) have dissimilar impacts on the sediment BCC in
      the tributary of Taihu Lake, while WWTPs exhibited the greatest potential to lead
      to biotic homogenization in river sediments. 

PMID- 27040537
TI  - Heavy metal accumulation in Diplodus annularis, Liza aurata, and Solea vulgaris
      relevant to their concentration in water and sediment from the southwestern
      Mediterranean (coast of Sfax).
AB  - The concentrations of heavy metals (Cd, Cu, Fe, Pb, Ni, and Zn) were measured in
      the liver, gills, and muscle of Solea vulgaris, Liza aurata, and Diplodus
      annularis, collected from the south coast of Sfax (Gabes Gulf, southwestern
      Mediterranean). The concentrations of heavy metals in water exhibited the
      following decreasing order (expressed in MUg l(-1)): Fe > Ni > Zn > Cu > Pb > Cd
      whereas the trend is somewhat different in sediments (mg kg(-1) D.W.) Fe > Zn >
      Pb > Ni > Cu > Cd. The levels of heavy metals varied significantly among fish
      species and tissues. Heavy metal levels were found generally higher in the liver
      and gills than the muscle in all species. The liver was the target organ for Cd,
      Cu, Fe, Ni, and Zn accumulation. Nickel and lead, however, exhibited their
      highest concentrations in the gills. The three studied fishes showed a difference
      in metals accumulation decreasing in following order S. vulgaris > D. annularis >
      L. aurata. Solea vulgaris with the highest TFwater, TFsediment, and metal
      concentrations in tissues would be considered as a potential bio-indicator in the
      south coast of Sfax for the assessment of environmental pollution status.
      Comparative studies with Luza zone indicate considerable bioaccumulation of heavy
      metals (Pb and Zn) in the various tissues of fish samples of the south coast of
      Sfax. 

PMID- 27040538
TI  - Usefulness of different vascular plant species for passive biomonitoring of
      Mediterranean rivers.
AB  - Choosing native vascular plants as nutrient and toxic element accumulators for
      passive biomonitoring of urban river quality is not an easy task in Mediterranean
      rivers, due to the particular climate determining high variations in river
      hydrology. To identify potential biomonitors for this area, the roots of seven
      species (Angelica sylvestris, Apium nodiflorum, Tradescantia fluminensis,
      Nasturtium officinale, Persicaria lapathifolia, Arctium lappa, Typha latifolia),
      growing in seven sites along the River Irno (Southern Italy), were collected in
      July 2010 and analyzed regarding their capability to accumulate Cd, Cr, Cu, Fe,
      K, Mg, Mn, Na, Ni, Pb, V, and Zn through atomic absorption spectrometry.
      Notwithstanding the expected different accumulation degree among the species,
      they highlighted similar spatial contamination gradients, and all of them
      appeared suitable, alone or in combination, for river passive biomonitoring. A.
      nodiflorum, in particular, appeared the best biomonitor for the River Irno, where
      severe anthropogenic impacts were detected: high Cu and Cd contamination from
      vine cultivation in the upper stretch, and Pb, Zn, and Mn contamination in the
      medium stretch from airborne dusts coming from a cast iron foundry. 

PMID- 27040539
TI  - Characteristics of size-segregated carbonaceous aerosols in the Beijing-Tianjin
      Hebei region.
AB  - Mass concentrations of organic carbon (OC) and elemental carbon (EC) in size
      resolved aerosols were investigated at four sites (three cities and one country)
      in the Beijing-Tianjin-Hebei region from September 2009 to August 2011. The size
      distributions of OC and EC presented large evolutions among rural and urban
      sites, and among four seasons, with highest peaks of OC and EC in fine mode in
      urban areas during winter. Geometric mean diameters (GMDs) of OC and EC in fine
      particles at urban sites during winter were lower than those at rural site mainly
      due to effects of fine particle coagulation and organic compound repartitioning.
      Fossil fuel emissions were a dominant source of OC and EC in urban areas, while
      biomass burning was a major source of OC and EC at rural site. Trajectory
      clustering and CWT analysis showed that regional transport was an important
      contributor to OC and EC in Beijing. 

PMID- 27040540
TI  - Biomarkers in the freshwater bivalve Corbicula fluminea confined downstream a
      domestic landfill leachate discharge.
AB  - Landfills represent a severe environmental problem mainly due to the generation
      of leachates, and this study aimed to evaluate sublethal effects of a domestic
      landfill leachate in the freshwater bivalve Corbicula fluminea. Clams were
      submitted to in situ tests along a stream, at three sites, representing
      increasing distances from the leachate discharge (Pq1, Pq2, and Pq3), for 1, 5,
      and 15 days. The following biomarkers were analyzed in the gills and digestive
      glands: 7-ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST)
      activities, multixenobiotic resistance mechanism (MXR), total antioxidant
      capacity (TAC), reactive oxygen species (ROS), and lipid peroxidation (LPO).
      Metallothionein (MT) content was determined in the gills and DNA damage in
      hemocytes. The mortality rate of animals during in situ tests was reduced as the
      distance from the leachate discharge source increased. On the other hand,
      biomarker results showed sublethal effects on C. fluminea confined at all sites
      of PqS. GST, TAC, ROS, and DNA damage were the most significant biomarkers for
      this species and should be considered for future monitoring and assessment of
      freshwater environments located in landfill areas. 

PMID- 27040541
TI  - The partitioning behavior of trace element and its distribution in the
      surrounding soil of a cement plant integrated utilization of hazardous wastes.
AB  - In the present study, the trace elements partitioning behavior during cement
      manufacture process were systemically investigated as well as their distribution
      behaviors in the soil surrounding a cement plant using hazardous waste as raw
      materials. In addition to the experimental analysis, the thermodynamic
      equilibrium calculations were simultaneously conducted. The results demonstrate
      that in the industrial-scale cement manufacture process, the trace elements can
      be classified into three groups according to their releasing behaviors. Hg is
      recognized as a highly volatile element, which almost totally partitions into the
      vapor phase. Co, Cu, Mn, V, and Cr are considered to be non-volatile elements,
      which are largely incorporated into the clinker. Meanwhile, Cd, Ba, As, Ni, Pb,
      and Zn can be classified into semi-volatile elements, as they are trapped into
      clinker to various degrees. Furthermore, the trace elements emitted into the flue
      gas can be adsorbed onto the fine particles, transport and deposit in the soil,
      and it is clarified here that the soil around the cement plant is moderately
      polluted by Cd, slightly polluted by As, Cr, Ba, Zn, yet rarely influenced by Co,
      Mn, Ni, Cu, Hg, and V elements. It was also estimated that the addition of wastes
      can efficiently reduce the consumption of raw materials and energy. The
      deciphered results can thus provide important insights for estimating the
      environmental impacts of the cement plant on its surroundings by utilizing wastes
      as raw materials. 

PMID- 27040542
TI  - Assessment of heavy metal contamination levels and toxicity in sediments and
      fishes from the Mediterranean Sea (southern coast of Sfax, Tunisia).
AB  - Contamination of heavy metals in sediment is regarded as a global crisis with a
      large share in industrializing cities like Sfax (Tunisia). Seven heavy metals
      such as Cadmium (Cd), Copper (Cu), Iron (Fe), Mercury (Hg), Nickel (Ni), Lead
      (Pb), and Zinc (Zn), and one metalloid such as Arsenic (As) in sediments and fish
      (D. annularis, L. aurata, and S. vulgaris) were investigated from the Southern
      coast of Sfax in Tunisia. The range of metals in sediments were 13.11-36; 4.42
      7.92; 8.23-28.56; 50,564-11,956; 2.9-6.8; 9.13-30.51; 65.06-151.50, and 47-546
      kg(-1) DW for As, Cd, Cu, Fe, Hg, Ni, Pb, and Zn. The level of studied metals in
      sediment samples exceeded the limits of the quality assessment guidelines (SQGs).
      The potential ecological risk index (PERI) proved that the investigated region
      could pose moderate risk for the aquatic biota. Metal bioaccumulation in the fish
      muscles varied significantly among species. Indeed, S. vulgaris and D. annularis
      accumulated higher amount of metal than L. aurata. The target hazard quotients
      (THQ) of individual heavy metals in fish, except for As and Hg, revealed safe
      levels for human consumption. Nevertheless, the total THQ indexes exceeded 1
      suggesting the combined effects on muscles fish, which may constitute a risk to
      population's health. 

PMID- 27040543
TI  - Environmental behaviors and potential ecological risks of heavy metals (Cd, Cr,
      Cu, Pb, and Zn) in multimedia in an oilfield in China.
AB  - The environmental behaviors of five heavy metals (Cd, Cr, Cu, Pb, and Zn) in a
      Chinese oilfield were investigated using a steady-state multimedia aquivalence
      (SMA) model. The modeling results showed good agreement with the actual measured
      values, with average residual errors of 0.69, 0.83, 0.35, 0.16, and 0.54
      logarithmic units for air, water, soil, sediment, and vegetation compartments,
      respectively. Model results indicated that most heavy metals were buried in
      sediment, and that transfers between adjacent compartments were mainly deposition
      from the water to the sediment compartment (48.59 %) and from the air to the soil
      compartment (47.74 %) via atmospheric dry/wet deposition. Sediment and soil were
      the dominant sinks, accounting for 68.80 and 25.26 % of all the heavy metals in
      the multimedia system, respectively. The potential ecological risks from the five
      heavy metals in the sediment and soil compartments were assessed by the potential
      ecological risk index (PERI). The assessment results demonstrate that the heavy
      metals presented low levels of ecological risk in the sediment compartment, and
      that Cd was the most significant contributor to the integrated potential
      ecological risk in the oilfield. The SMA model provided useful simulations of the
      transport and fate of heavy metals and is a useful tool for ecological risk
      assessment and contaminated site management. 

PMID- 27040544
TI  - Estimating renewal timescales with residence time and connectivity in an urban
      man-made lake in China.
AB  - Residence times and connectivity are computed for 12 subregions in an urban man
      made lake in China using a high-resolution tracer-transport model. The renewal
      timescales are explicitly defined and computed for two groups of four freshwater
      inflow scenarios related to water diversion projects. First, the timescale values
      are computed and compared using different computational criteria for the upper
      limit of integration in the residence time equation. The sensitivity analysis
      suggests that a calculation time of 300 days is necessary to satisfy the relative
      error (0.001) and 5 % cutoff value criteria. Secondly, the residence times can
      range from 1.5 to 102 and 1.0 to 66 days under low and high flow conditions,
      respectively. Water in the inner lake would reside in the lake for less than 66
      days prior to exiting the region of interest. The timescale values can be applied
      to impact studies that investigate the extent of sudden water pollution events
      that initially affect a subdomain of a lake. Finally, the lacustrine residence
      times are decomposed into the different subregion residence times, resulting in a
      connectivity matrix. This matrix can illustrate preferential connections among
      the individual subregions and reveal hidden patterns relating to local
      hydrodynamics in the lake. 

PMID- 27040545
TI  - Magnetic iron species highly dispersed over silica: use as catalysts for removal
      of pollutants in water.
AB  - Fe2O3-SiO2 composites were prepared by impregnation (sample FeIMP) or doping
      (sample FeDOP) in the structure of porous silica. The dye removal capacity of the
      materials was investigated through adsorption and oxidation studies of methylene
      blue and rhodamine B. N2 adsorption/desorption measurements on FeIMP and FeDOP
      resulted in specific areas of 27 and 235 m2 g-1, respectively. Mossbauer
      spectroscopy and XRD data detected hematite and maghemite as the iron phases in
      the samples FeIMP and FeDOP, respectively. Adsorption isotherms and kinetic
      studies of the dyes were better fitted in DKR model for FeDOP, where the process
      follows a pseudo-second order with the interparticle diffusion step being the
      rate-limiting step. On the other hand, FeIMP has better fit in the Langmuir
      model. Photocatalytic activity was observed in FeDOP under UV irradiation by the
      presence of reaction-hydroxylated intermediates for MB (m/z = 301) and RhB (m/z =
      459). However, the photocatalytic activity was strongly influenced by the
      adsorption affinity between dye/catalyst. Photogenerated holes are the species
      responsible for the dye degradation when the adsorption is too strong, while
      hydroxyl radical action will be favored when the adsorption is not vigorous as
      detected by ESI-MS. Graphical Abstract Action of photogenerated holes and free
      electrons into the photocatalytically mechanism of methylene blue degradation
      over a semiconductor.

PMID- 27040546
TI  - Occurrence and risk assessment of tetracycline antibiotics in soil from organic
      vegetable farms in a subtropical city, south China.
AB  - This study investigated the occurrence of tetracycline antibiotics in soils from
      different organic vegetable farms in Guangzhou, a subtropical city, South China
      and evaluated their ecological risk. Four tetracycline compounds
      (oxytetracycline, tetracycline, chlortetracycline, and doxycycline) were
      extracted ultrasonically from soil samples (n = 69), with a solid-phase
      extraction cleanup, and were then measured by high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS). The results showed that
      four compounds were detected in all samples, with the concentrations of the
      individual compounds ranging from 0.04 to 184.8 MUg/kg (dry weight). The
      concentrations of tetracycline compounds in the soils from different vegetable
      farms varied greatly, but their patterns of distribution were similar.
      Doxycycline was the predominant compound with a mean of 21.87 MUg/kg, followed by
      chlortetracycline. The concentrations of doxycycline and chlortetracycline in
      7.46 % of the samples were higher than the ecotoxic effect trigger value (100
      MUg/kg) set by the Steering Committee of Veterinary International Committee on
      Harmonization. Additionally, the concentrations of tetracyclines in greenhouse
      soils were significantly lower than those in open-field soils. Risk assessment
      based on single compound exposure showed that doxycycline could pose medium or
      high risks. Compared with other studies, the levels of tetracyclines in this
      study were relatively low. The hypothesis that antibiotic residues in the soil of
      organic farms fertilized with manure are higher than in the soils of conventional
      farms was not supported in the area studied due to the high levels of moisture,
      temperature, and microbial activity. 

PMID- 27040547
TI  - Spatial and temporal characteristics of air quality and air pollutants in 2013 in
      Beijing.
AB  - Air pollution has become an ever more critical issue in Beijing in more recent
      years. In this study, we use the air quality index (AQI), corresponding primary
      pollutant types and meteorological data which are collected at 16 monitoring
      stations in Beijing between January 2013 and December, 2013 studying the spatial
      and temporal variations of air quality and air pollutants. The results show that
      PM2.5 was the most serious pollutant, followed by O3. The average PM2.5 mass
      concentration was 119.5 +/- 13.8 MUg m(-3) in Beijing. In addition, the air
      quality varies across different seasons. More specifically, winter season showed
      the worst air quality. Moreover, while particulate matter (PM2.5 and PM10)
      concentrations were relatively higher in the spring and winter seasons, gaseous
      pollutants (O3 and NO2) were more serious in the summer and autumn. In terms of
      spatial heterogeneity, the findings showed that AQI and PM2.5 concentrations were
      higher in south and lower in the north of the city, and the O3 showed exactly a
      pattern with the opposite direction-higher in the north and lower in the south.
      NO2 was found to have a greater impact on the central region compared with that
      in other regions. Furthermore, PM2.5 was found to be positively correlated with
      the relative humidity, but negatively correlated with wind speed and atmospheric
      pressure (P < 0.01). However, the dominant meteorological factors that influence
      the PM2.5 concentrations varied in different seasons. The results in this paper
      provide additional information for the effective control of the air pollution in
      Beijing. 

PMID- 27040548
TI  - Artificial neural network models for prediction of daily fine particulate matter
      concentrations in Algiers.
AB  - Neural network (NN) models were evaluated for the prediction of suspended
      particulates with aerodynamic diameter less than 10-MUm (PM10) concentrations.
      The model evaluation work considered the sequential hourly concentration time
      series of PM10, which were measured at El Hamma station in Algiers. Artificial
      neural network models were developed using a combination of meteorological and
      time-scale as input variables. The results were rather satisfactory, with values
      of the coefficient of correlation (R (2)) for independent test sets ranging
      between 0.60 and 0.85 and values of the index of agreement (IA) between 0.87 and
      0.96. In addition, the root mean square error (RMSE), the mean absolute error
      (MAE), the normalized mean squared error (NMSE), the absolute relative percentage
      error (ARPE), the fractional bias (FB), and the fractional variance (FS) were
      calculated to assess the performance of the model. It was seen that the overall
      performance of model 3 was better than models 1 and 2. 

PMID- 27040549
TI  - A comprehensive assessment of agricultural intensification scenarios for the
      Dongting Lake basin in south-central China in 2030.
AB  - To explore the future of the material demand, pollutant emission, production, and
      arable land area surrounding the Dongting Lake basin, and to find a potential
      solution for agricultural development, this study assumes the following four
      agriculture intensification scenarios: the natural development scenario (ND), the
      production development scenario (PD), the moderate intensification scenario (MI),
      and the local resilience scenario (LR). The scenarios focus on different
      developmental patterns (natural development, short-term production growth, long
      term sustainability, or self-sufficiency).The result shows to satisfy the food
      demand in 2030, and the production of crop and meat will be 26.96, 30.25, 28.05,
      and 16.27 * 10(6) t in ND, PD, MI, and LR, respectively; more than 1.78 * 10(6)
      ha of arable land is needed. Compared with the year 2012, the material input and
      pollutant output will increase by a maximum of 18.32 and 122.31 %, respectively.
      By classifying the environmental risk into four categories-greenhouse gas
      emission, air pollution, eutrophication, and ecotoxicity-the composite
      environmental risk index (CER) is calculated. The CER in PD was the highest,
      followed by that in ND, LR, and MI. Due to the production allocation within the
      35 cities and counties, the spatial distribution of CER is more homogenous in PD
      and MI than in ND. The analysis of the scenarios reveals that through
      technological improvement and spatial allocation of agricultural production,
      scenario MI could be a potential direction for the government to design a
      sustainable agricultural-environmental system. 

PMID- 27040550
TI  - Modeling the reactivities of hydroxyl radical and ozone towards atmospheric
      organic chemicals using quantitative structure-reactivity relationship
      approaches.
AB  - The persistence and the removal of organic chemicals from the atmosphere are
      largely determined by their reactions with the OH radical and O3. Experimental
      determinations of the kinetic rate constants of OH and O3 with a large number of
      chemicals are tedious and resource intensive and development of computational
      approaches has widely been advocated. Recently, ensemble machine learning (EML)
      methods have emerged as unbiased tools to establish relationship between
      independent and dependent variables having a nonlinear dependence. In this study,
      EML-based, temperature-dependent quantitative structure-reactivity relationship
      (QSRR) models have been developed for predicting the kinetic rate constants for
      OH (kOH) and O3 (kO3) reactions with diverse chemicals. Structural diversity of
      chemicals was evaluated using a Tanimoto similarity index. The generalization and
      prediction abilities of the constructed models were established through rigorous
      internal and external validation performed employing statistical checks. In test
      data, the EML QSRR models yielded correlation (R (2)) of >=0.91 between the
      measured and the predicted reactivities. The applicability domains of the
      constructed models were determined using methods based on descriptors range,
      Euclidean distance, leverage, and standardization approaches. The prediction
      accuracies for the higher reactivity compounds were relatively better than those
      of the low reactivity compounds. Proposed EML QSRR models performed well and
      outperformed the previous reports. The proposed QSRR models can make predictions
      of rate constants at different temperatures. The proposed models can be useful
      tools in predicting the reactivities of chemicals towards OH radical and O3 in
      the atmosphere. 

PMID- 27040551
TI  - Mechanical thrombectomy in cardiac myxoma stroke: a case report and review of the
      literature.
AB  - Cardiac myxoma is the most common primary tumor of the heart. It is a rare cause
      of acute ischemic stroke and commonly not detected until after the stroke. There
      is no current guideline for the treatment of cardiac myxoma stroke and only a few
      cases of mechanical thrombectomy have been reported. We present a case of cardiac
      myxoma stroke in a 4-year-old boy treated with a stent-retrieval device and
      review the literature describing the safety and efficacy of mechanical
      thrombectomy in cardiac myxoma stroke. We also describe imaging features of the
      myxoma clot on susceptibility weighted images.

PMID- 27040552
TI  - Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage.
AB  - BACKGROUND: It is believed that increased intracranial pressure immediately after
      subarachnoid hemorrhage (SAH) causes extensive brain ischemia and results in
      worsening clinical status. Arterial flow to the cerebral surfaces is clinically
      well maintained during clipping surgery regardless of the severity of the World
      Federation of Neurological Societies grade after SAH. To explore what kinds of
      changes occur in the cortical microcirculation, not at the cerebral surface, we
      examined cortical microcirculation after SAH using two-photon laser scanning
      microscopy (TPLSM). METHODS: SAH was induced in mice with an endovascular
      perforation model. Following continuous injection of rhodamine 6G, velocities of
      labeled platelets and leukocytes and unlabeled red blood cells (RBCs) were
      measured in the cortical capillaries 60 min after SAH with a line-scan method
      using TPLSM, and the data were compared to a sham group and P-selectin monoclonal
      antibody-treated group. RESULTS: Velocities of leukocytes, platelets, and RBCs in
      capillaries decreased significantly 60 min after SAH. Rolling and adherent
      leukocytes suddenly prevented other blood cells from flowing in the capillaries.
      Flowing blood cells also decreased significantly in each capillary after SAH.
      This no-reflow phenomenon induced by plugging leukocytes was often observed in
      the SAH group but not in the sham group. The decreased velocities of blood cells
      were reversed by pretreatment with the monoclonal antibody of P-selection, an
      adhesion molecule expressed on the surfaces of both endothelial cells and
      platelets. CONCLUSIONS: SAH caused sudden worsening of cortical microcirculation
      at the onset. Leukocyte plugging in capillaries is one of the reasons why
      cortical microcirculation is aggravated after SAH.

PMID- 27040554
TI  - Bowmanella dokdonensis sp. nov., a novel exoelectrogenic bacterium isolated from
      the seawater of Dokdo, Korea.
AB  - A Gram-negative, motile, and rod-shaped bacterial strain, UDC354(T), was isolated
      from the seawater of Dokdo, Korea. The strain UDC354(T) displayed optimal growth
      at 30-37  degrees C in the presence of 0-2 % (w/v) NaCl at pH 8. Strain UDC354(T)
      was found to contain Q-8 and 9 as isoprenoid ubiquinones; C16:0 (22.9 %), summed
      feature 3 (iso-C15:0 2-OH and C16:1 omega7c) (21.4 %) and C18:1 omega7c (12.2 %)
      as the major fatty acids; and diphosphatidylglycerol, phosphatidylglycerol, and
      phosphatidylethanolamine as the major polar lipids. The DNA G+C content was found
      to be 54.1 mol %. Phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain UDC354(T) belongs to the genus Bowmanella, of the family
      Alteromonadaceae, and is closely related to Bowmanella pacifica W3-3A(T) (95.2 %)
      and Bowmanella denitrificans BD1(T) (95.0 %). It was found that strain UDC354(T)
      is exoelectrogenic and is capable of generating 6.6 MUW/cm(3) in marine broth in
      the microbial fuel cells. Based on the analysis of the phenotypic, chemotypic and
      phylogenetic characteristics, a new species, Bowmanella dokdonensis sp. nov. is
      proposed. The type strain is UDC354(T) (=KCTC 42147(T)=JCM 30855(T)). 

PMID- 27040553
TI  - Clinical outcome and osteoarthritic changes after surgical treatment of isolated
      capitulum humeri fractures with a minimum follow-up of five years.
AB  - PURPOSE: The aim of this study was to evaluate the functional outcome of patients
      treated for a fracture of the capitulum humeri and to analyze the grade of
      osteoarthritic changes. METHODS: Patients undergoing surgical reconstruction of
      isolated capitulum humeri fractures were included in a retrospective comparative
      analysis. Fractures were classified according to the Arbeitsgemeinschaft fur
      Osteosynthesefragen (AO) and Dubberley and were functionally evaluated by the
      American Shoulder and Elbow Surgeons Score (ASES) and the Mayo Elbow Performance
      Index (MEPI). Levels of arthritic changes were measured with the Broberg and
      Morrey Score. Frequency of complications was evaluated whereby all results were
      compared to the ipsilateral, unaffected side. RESULTS: Thirteen patients, ten
      females (76.9 %) and three males (23.1 %), with a mean age of 48.7 +/- 13.3 years
      were included in the study. Long-term follow-up range of motion (ROM) in the
      sagittal plane was significantly influenced by time of surgery (p < 0.001), and
      long-term follow-up with respect to pronation and supination by ROM of the
      healthy control (p < 0.05). The average ASES score was 37.8, and the Mayo Elbow
      Performance Index (MEPI) was 92.7. The mean level of degenerative arthritic
      changes was 1.9 +/- 0.6 on the fractured side and significantly less (0.8 +/-
      0.8) on the healthy side (pF-test < 0.001). At a mean follow-up of 118.5 +/- 52.4
      months neither nonunion nor avascular necrosis were observed in any case.
      However, six cases of heterotopic ossification were identified. CONCLUSIONS:
      Satisfying functional outcomes and a low rate of osteoarthritic changes can be
      expected after the presented open reduction and internal fixation of capitulum
      humeri fractures. LEVEL OF EVIDENCE: Level IV - Case series; therapeutic study.

PMID- 27040555
TI  - An Instrument to Prepare for Acute Care of the Individual with Autism Spectrum
      Disorder in the Emergency Department.
AB  - We present an instrument to allow individuals with autism spectrum disorder,
      their families and/or their caregivers to prepare emergency department staff for
      the care needs of this patient population ahead of acute presentation.

PMID- 27040556
TI  - Brief Report: Insistence on Sameness, Anxiety, and Social Motivation in Children
      with Autism Spectrum Disorder.
AB  - While the function of restricted repetitive behaviors (RRBs) in autism spectrum
      disorder (ASD) is unclear, RRBs may function as anxiety reduction strategies
      (Joosten et al. J Autism Dev Disord 39(3):521-531, 2009. Moreover, anxiety in ASD
      is associated with low social motivation (Swain et al. J Autism Dev Disord, 2015.
      The present study examined social motivation as a mediator between anxiety and
      RRBs in a sample of 44 children (2-17 years old; 80 % male) with ASD. The
      relationship between anxiety and IS, but not other RRBs, was partially mediated
      by social motivation. These findings suggest anxiety is linked to social
      motivation deficits in children with ASD, which may increase ritualized behaviors
      and difficulties with changes in routine. Implications are discussed for
      differing functions and treatment of RRB domains.

PMID- 27040557
TI  - Long-Term Effects of CBT on Social Impairment in Adolescents with ASD.
AB  - Anxiety interventions involving social skills training and CBT for youth with ASD
      have shown promise, but few studies have examined the effects on social
      functioning or the maintenance of treatment gains. This study evaluated change in
      social skills during a randomized controlled trial of CBT and during the 1-year
      follow-up for 25 adolescents with ASD and anxiety. We examined the effect of
      pretreatment social anxiety and loneliness on treatment response. Social
      impairment improved during treatment and continued to improve through the 3-month
      follow-up. Although adolescents with higher social anxiety had greater
      pretreatment social impairment, they showed steeper improvement in social skills
      during treatment. Loneliness was not a significant predictor of change during
      treatment. CBT targeting social skills and anxiety can lead to long-term
      improvements in social functioning.

PMID- 27040558
TI  - Initial severity of motor and non-motor disabilities in patients with facial
      palsy: an assessment using patient-reported outcome measures.
AB  - Patients with facial palsy (FP) not only suffer from their facial movement
      disorder, but also from social and psychological disabilities. These can be
      assessed by patient-reported outcome measures (PROMs) like the quality-of-life
      Short-Form 36 Item Questionnaire (SF36) or FP-specific instruments like the
      Facial Clinimetric Evaluation Scale (FaCE) or the Facial Disability Index (FDI).
      Not much is known about factors influencing PROMs in patients with FP. We
      identified predictors for baseline SF36, FaCE, and FDI scoring in 256 patients
      with unilateral peripheral FP using univariate correlation and multivariate
      linear regression analyses. Mean age was 52 +/- 18 years. 153 patients (60 %)
      were female. 90 patients (31 %) and 176 patients (69 %) were first seen <90 or
      >90 days after onset, respectively, i.e., with acute or chronic FP. House
      Brackmann grading was 3.9 +/- 1.4. FaCE subscores varied from 41 +/- 28 to 71 +/-
      26, FDI scores from 65 +/- 20 to 70 +/- 22, and SF36 domains from 52 +/- 20 to 80
      +/- 24. Older age, female gender, higher House-Brackmann grading, and initial
      assessment >90 days after onset were independent predictors for lower FaCE
      subscores and partly for lower FDI subscores (all p < 0.05). Older age and female
      gender were best predictors for lower results in SF36 domains. Comorbidity was
      associated with lower SF General health perception and lower SF36 Emotional role
      (all p < 0.05). Specific PROMs reveal that older and female patients and patients
      with chronic FP suffer particularly from motor and non-motor disabilities related
      to FP. Comorbidity unrelated to the FP could additionally impact the quality of
      life of patients with FP.

PMID- 27040559
TI  - Clinical and morphological aspects of adenocarcinomas of the intestinal type in
      the inner nose: a retrospective multicenter analysis.
AB  - Clinical and histological parameters from 117 patients with wood dust-related
      sinonasal adenocarcinomas of intestinal type (ITAC) were analyzed and correlated
      with a follow-up period of 5 years at least. The rate of survival for 5 years was
      53.1 % and for 10 years 30.2 %. Only 33 patients were free of disease. 74.2 % of
      patients with recurrences died in relation to ITAC. As expected, tumors of T4
      category had the worst prognosis. The mucus content of a tumor was the most
      important histological parameter. Endonasal methods of surgery had no more
      positive survival rates after 5 years. An effect of radiotherapy has to be in
      discussion. The high incidence of tumor recurrences requires control examinations
      consistently. 

PMID- 27040560
TI  - Effects of light wavelength on MEG ERD/ERS during a working memory task.
AB  - We investigated the effects of light wavelengths on cortical oscillatory activity
      associated with working memory processes. Cortical activity responses were
      measured using magnetoencephalography (MEG) while participants performed an
      auditory Sternberg memory task during exposure to light of different wavelength.
      Each trial of the memory task consisted of four words presented as a memory set
      and one word presented as a probe. All words were presented audibly. Participants
      were instructed to indicate whether the probe word was or was not presented
      within the memory set. A total of 90 trials were conducted under the light
      exposure. Event-related synchronization (ERS) and event-related desynchronization
      responses in the alpha frequency range during the task were analyzed. Results
      showed that, during memory encoding, ERS responses were significantly greater in
      the short-wavelength (blue) light condition than in the middle-wavelength (green)
      light condition, approximately 20-30min after the onset of light exposure.
      Behavioral performance was very high throughout the experiment and there was no
      difference between the light conditions. Although the light effects were not
      observed in behavior, the result of ERS suggests that 20-30min of exposure to
      blue light enhances cortical activity related to active memory maintenance and/or
      attention to auditory stimuli.

PMID- 27040561
TI  - [Same words, different meanings: How epidemiological terminology struggles with
      population health intervention research].
AB  - Public health research differs from clinical epidemiological research in that its
      focus is primarily on the population level social and structural determinants of
      individual health and the interventions that might ameliorate them, rather than
      having a primary focus on individual-level risks. It is typically concerned with
      the proximal and distal causes of health problems, and their location within
      complex systems, more than with single exposures. Thus, epidemiological terms and
      concepts may have very different implications when used in the context of
      population health. This paper considers some key differences in relation to terms
      like 'population', 'baseline', 'control group' 'outcome' and 'adverse effects'.
      Even the concept of an 'intervention' often needs careful handling. The paper
      concludes that there is a need for an expanded, and more realistic use of these
      terms in the population health intervention research context. 

PMID- 27040562
TI  - Evaluation of a pulsed xenon ultraviolet light device for isolation room
      disinfection in a United Kingdom hospital.
AB  - BACKGROUND: Pathogen transmission from contaminated surfaces can cause hospital
      associated infections. Although pulsed xenon ultraviolet (PX-UV) light devices
      have been shown to decrease hospital room bioburden in the United States, their
      effectiveness in United Kingdom (UK) hospitals is less understood. METHODS: Forty
      isolation rooms at the Queens Hospital (700 beds) in North London, UK, were
      sampled for aerobic bacteria after patient discharge, after manual cleaning with
      a hypochlorous acid-troclosene sodium solution, and after PX-UV disinfection. PX
      UV device efficacy on known organisms was tested by exposing inoculated agar
      plates in a nonpatient care area. Turnaround times for device usage were
      recorded, and a survey of hospital staff for perceptions of the device was
      undertaken. RESULTS: After PX-UV disinfection, the bacterial contamination
      measured in colony forming units (CFU) decreased by 78.4%, a 91% reduction from
      initial bioburden levels prior to terminal cleaning. PX-UV exposure resulted in a
      5-log CFU reduction for multidrug-resistant organisms (MDROs) on spiked plates.
      The average device turnaround time was 1 hour, with minimal impact on patient
      throughput. Ward staff were enthusiastic about device deployment, and device
      operators reported physical comfort in usage. CONCLUSIONS: PX-UV use decreased
      bioburden in patient discharge rooms and on agar plates spiked with MDROs. The
      implementation of the PX-UV device was well received by hospital cleaning and
      ward staff, with minimal disruption to patient flow.

PMID- 27040563
TI  - Design study to develop screen savers aimed at improving hand hygiene behavior.
AB  - BACKGROUND: Displaying screen savers with gain-framed messages are effective to
      improve hand hygiene, but the design of screen savers has not been studied yet.
      METHODS: Based on the literature, scientific propositions were developed for the
      design of screen savers, exploring 2 strategies to subconsciously influence hand
      hygiene behavior; the first was to gain attention, and the second was to exert
      peer pressure. The designed screen savers were tested for attention with an eye
      tracking study (N = 27) and for the influence of peer pressure with a
      questionnaire (N = 25). RESULTS: Twenty-five propositions for gaining attention
      concerned the format and color of the screen saver itself and color, position,
      and style of visual and text elements. Seven propositions for peer pressure
      concerned the influence of peers, role models, and feelings of being watched. Eye
      tracking measurements showed that text on the 4 screen savers based on
      propositions gained more, earlier, and longer attention and the visual elements
      gained earlier and longer attention than the control screen savers. The
      questionnaire results showed that feelings of peer pressure were evoked by 3
      screen savers; of these, one was not based on propositions. CONCLUSIONS: Screen
      savers designed according to scientific propositions for visual attention and
      peer pressure have the potential to alter hand hygiene behavior.

PMID- 27040564
TI  - Reproducible elimination of Clostridium difficile spores using a clinical area
      washer disinfector in 3 different health care sites.
AB  - BACKGROUND: Following a Clostridium difficile infection outbreak, the Infection
      Prevention and Control team at our institution queried the risk of transmission
      via bedpans reprocessed in washer disinfectors (WDs). This study's objective was
      to determine the effectiveness of the mechanical action, detergent, and
      temperature on the eradication of C difficile spores in 1 type of WD model.
      MATERIALS AND METHODS: Three types of reusable bedpans/pots were inoculated with
      sterile human feces that contained 1 * 10(7) CFU/mL C difficile spores. The 0.3
      mL fecal-spore suspension was inoculated in sealed cryovials. These items were
      reprocessed using the longest wash cycle of WDs in 9 clinical units, and then
      tested for residual C difficile spores. The number of colonies on each replicate
      organism detection and counting plate was recorded after anaerobic incubation at
      35 degrees C for 48 hours, and the log reduction was calculated. RESULTS: All 9
      WDs met the manufacturer's operational specifications. Forty-three (96%) of 45
      bedpans had no viable spores (>5.9 log10C difficile spore reduction). Two bedpans
      had 1 to 2 spores remaining. Viable C difficile spores were isolated from all 9
      cryovials. DISCUSSION AND CONCLUSIONS: Results demonstrated that when operating
      the WD as stipulated, C difficile spores were satisfactorily eliminated from
      bedpan surfaces. Temperature alone was insufficient to kill C difficile spores.
      It also suggested the importance of staff training, machine maintenance, and WD
      purchase specifications.

PMID- 27040565
TI  - Ventilator-associated pneumonia rates in critical care units in 3 Arabian Gulf
      countries: A 6-year surveillance study.
AB  - BACKGROUND: Data estimating the rates of ventilator-associated pneumonia (VAP) in
      critical patients in Gulf Cooperation Council (GCC) countries are very limited.
      The aim of this study was to estimate VAP rates in GCC hospitals and to compare
      rates with published reports of the U.S. National Healthcare Safety Network
      (NHSN) and International Nosocomial Infection Control Consortium (INICC).
      METHODS: VAP rates and ventilator utilization between 2008 and 2013 were
      calculated from aggregate VAP surveillance data using NHSN methodology pooled
      from 6 hospitals in 3 GCC countries: Saudi Arabia, Oman, and Bahrain. The
      standardized infection ratios of VAP in GCC hospitals were compared with
      published reports of the NHSN and INICC. RESULTS: A total of 368 VAP events were
      diagnosed during a 6-year period covering 76,749 ventilator days and 134,994
      patient days. The overall VAP rate was 4.8 per 1,000 ventilator days (95%
      confidence interval, 4.3-5.3), with an overall ventilator utilization of 0.57.
      The VAP rates showed a wide variability between different types of intensive care
      units (ICUs) and were decreasing over time. After adjusting for the differences
      in ICU type, the risk of VAP in GCC hospitals was 217% higher than NHSN hospitals
      and 69% lower than INICC hospitals. CONCLUSIONS: The risk of VAP in ICU patients
      in GCC countries is higher than pooled U.S. VAP rates but lower than pooled rates
      from developing countries participating in the INICC.

PMID- 27040566
TI  - Contacts between health care workers and patients in a short-stay geriatric unit
      during the peak of a seasonal influenza epidemic compared with a nonepidemic
      period.
AB  - BACKGROUND: Patterns of contacts between health care workers and patients during
      seasonal epidemics are unknown. Our study objective was to compare the number and
      duration of contacts between health care workers and patients during a
      nonepidemic period versus a community influenza epidemic, and to identify
      supercontactors. METHODS: Our observational study was conducted in a short-stay
      geriatric unit of a university hospital. Contacts between individuals were
      recorded by active radio frequency identification devices. Contact patterns were
      compared between 2 periods according to contact number and duration. Each care
      period lasted 5 days in the nonepidemic and influenza epidemic periods. RESULTS:
      The study included 21 medical doctors, 43 nurses, and 56 patients. In total,
      3,200 contacts (61.4%; 152,700 seconds) were recorded during the nonepidemic
      period, with 2,013 contacts (38.6%; 92,740 seconds) in the epidemic period (P =
      .007). More cumulative contacts occurred during the nonepidemic period between
      nurses and patients (n = 2,638 [82%] vs n = 1,599 [79%]), but not between
      patients (n = 56 [18%] vs n = 414 [21%]). Contact duration between nurses and
      patients lasted longer during the nonepidemic period (P = .04). During the
      epidemic period, 6 nurses (15%) considered to be supercontactors accounted for
      44.3% of the total number of contacts with patients. CONCLUSION: The pattern of
      contacts between individuals differed according to the presence or not of the
      community influenza peak that might have influenced the risk of nosocomial
      influenza.

PMID- 27040567
TI  - In-flight transmission of measles: Time to update the guidelines?

PMID- 27040568
TI  - Dialysis Event Surveillance Report: National Healthcare Safety Network data
      summary, January 2007 through April 2011.
AB  - A total of 24,092 adverse events in hemodialysis outpatients during January 2007
      through April 2011 were reported to the National Healthcare Safety Network. Of
      2,656 bloodstream infections, 67.3% were in patients with central venous
      catheters. For all events, rates associated with central venous catheters were
      higher than for other vascular access types.

PMID- 27040569
TI  - Introducing automated hand hygiene surveillance to an Australian hospital:
      Mirroring the HOW2 Benchmark Study.
AB  - BACKGROUND: Human auditing and collating hand hygiene compliance data take
      hundreds of hours. We report on 24/7 overt observations to establish adjusted
      average daily hand hygiene opportunities (HHOs) used as the denominator in an
      automated surveillance that reports daily compliance rates. METHODS: Overt 24/7
      automated surveillance collected HHOs in medical and surgical wards. Accredited
      auditors observed health care workers' interaction between patient and patient
      zones to collect the total number of HHOs, indications, and compliance and
      noncompliance. Automated surveillance captured compliance (ie, events) via low
      power radio connected to alcohol-based handrub (ABHR) dispensers. Events were
      divided by HHOs, adjusted for daily patient-to-nurse ratio, to establish daily
      rates. RESULTS: Human auditors collected 21,450 HHOs during 24/7 with 1,532
      average unadjusted HHOs per day. This was 4.4 times larger than the minimum ward
      sample required for accreditation. The average adjusted HHOs for ABHR alone on
      the medical ward was 63 HHOs per patient day and 40 HHOs per patient day on the
      surgical ward. From July 1, 2014-July 31, 2015 the automated surveillance system
      collected 889,968 events. CONCLUSIONS: Automated surveillance collects 4 times
      the amount of data on each ward per day than a human auditor usually collects for
      a quarterly compliance report.

PMID- 27040570
TI  - An average hand hygiene day for nurses and physicians: The burden is not equal.
AB  - BACKGROUND: To understand whether the burden of hand hygiene contributes to poor
      compliance we measured the daily number of hand hygiene opportunities (HHOs) by
      shift for nurses and physicians in 2 wards in a 850-bed university teaching
      hospital. METHODS: On each ward 4 trained auditors collected the number of HHOs
      and compliance events for 24 hours over 7 days. Twenty-one thousand four hundred
      fifty HHOs were collected from a medical and a surgical ward. The proportion of
      alcohol-based handrub used daily, the burden of hand hygiene, and compliance
      rates were calculated separately for nurses and physicians. RESULTS: The average
      indication for alcohol-based handrub cleansing represented 68% of all HHOs.
      Nurses had an average burden of 55 HHOs per 24 hours or 27 HHOs per shift, 3
      times higher than the burden for physicians, who had 16 HHOs per 24 hours or 8
      HHOs per shift. Overt observations of the weekly compliance identified nurses had
      1.5 times higher compliance than physicians: 76% and 52% (P < .01), respectively.
      CONCLUSIONS: Nurses have 3 times more HHOs than physicians, yet nurses have 1.5
      times higher compliance than physicians. Hand hygiene compliance in physicians
      cannot be explained by burden of HHOs.

PMID- 27040571
TI  - Quantifying the rambunctious journey of the anesthesia provider's hands during
      simulated, routine care.
AB  - BACKGROUND: The role of anesthesia providers in dispersing potentially pathogenic
      material from one patient to another during intraoperative care needs further
      study. In this study we aimed (1) to quantify the dispersion of a surrogate
      pathogen from a simulated patient's mouth to the anesthesia workstation during
      routine anesthetic induction, (2) to test the hypothesis that there would be
      fewer contamination sites by providers who used a double-gloving technique, and
      (3) to examine the effectiveness of between-case anesthesia apparatus
      disinfection. METHODS: Twenty subjects were randomized to a single pair of gloves
      group (group 1) or a double-gloved group (group 2) and completed a simulated
      general anesthesia induction, completing a standardized set of interventions.
      Dispersion of a surrogate pathogen dye placed in the oral cavity of the simulated
      patient was tracked by a blinded observer and photography. Standard cleaning of
      the workstation was performed, and residual dye was quantified. Group performance
      was plotted using regression analysis and rate of contamination compared using
      parametric statistics. RESULTS: Group 1 contaminated an average of 16.0 (SEM =
      0.89) sites compared with group 2, who contaminated an average of 7.6 (SEM =
      0.85). The cart drawers, gas flow dials, medication vials, and ventilator
      controls were significantly contaminated by group 1, but not by group 2 (P < .05
      in all cases). There were similar rates of contamination in both groups for the
      airway equipment, breathing system, intravenous access ports, and the roll of
      tape used to secure the endotracheal tube. Once the airway management phase of
      the induction ended, new site contamination continued at a high rate in group 1
      but not group 2. CONCLUSIONS: A double-gloving technique was associated with less
      spread of an oral inoculum to the workstation but was not uniformly protective.
      Between-case cleaning was ineffective in removing the contaminant, indicating
      that biologic material from one patient may be present when subsequent patients
      are cared for. This suggests risks for the current patient (eg, skin or oral site
      transfer to an intravenous site) and also may place future patients at risk.
      Importantly, using models that simulate actual clinical events can inform
      clinical practice and decipher challenging areas of ergonomics.

PMID- 27040572
TI  - Sickness presenteeism in clinical clerks: Negatively reinforced behavior or an
      issue of patient safety?
AB  - BACKGROUND: The purpose of this study was to investigate sickness presenteeism in
      medical students and to understand the factors that may promote this behavior.
      METHODS: All 178 final year medical students (clinical clerks) at the University
      of Calgary, Class of 2014 were invited to complete an online, anonymous, cross
      sectional survey. After completing each mandatory rotation, students were sent a
      link to the online survey. Students were asked to report days of illness and
      whether they attended clinical or educational activities while ill. Students were
      also asked about consequences of missed days and reasons for attending while ill.
      RESULTS: Out of a possible 1,068 surveys, 549 surveys were returned, reflecting a
      51% response rate. Overall, 37.0% +/- 11.8% of the respondents reported attending
      while experiencing symptoms suggestive of a contagious illness. Overall, the odds
      of presenteeism (ie, attending while ill/absent while ill) for all clerkship
      rotations were 4.92. The most frequent reasons (56%) were concerns regarding
      evaluation or the impact that missing time from the rotation would have on their
      learning. CONCLUSIONS: Sickness presenteeism is common among medical students.
      Relevant factors may be different for students than other health care workers.
      Medical educators should be aware of these factors when developing policies to
      help promote professionalism and patient safety.

PMID- 27040573
TI  - Monitoring Ionizing Radiation Exposure for Cardiotoxic Effects of Breast Cancer
      Treatment.
AB  - Serial assessments of left ventricular ejection fraction (LVEF) are customary in
      patients with breast cancer receiving trastuzumab. Radionuclide angiography (RNA)
      is often used; however, a typical monitoring schedule could include 5 scans in a
      year. We evaluated the proportion of imaging-related ionizing radiation
      attributable to RNA in 115 patients with breast cancer, from 3 medical centers in
      the United States, Ireland, and Japan, who completed 12 months of trastuzumab
      treatment. Estimated radiation dose (ERD) was used to calculate exposure
      associated with imaging procedures spanning the 18 months before and after
      trastuzumab therapy. In addition, 20 cardiologists and oncologists from
      participating centers were surveyed for their opinions regarding the contribution
      of RNA to overall radiation exposure during trastuzumab treatment. When RNA was
      used to monitor LVEF, the mean ERD from imaging was substantial (34 +/- 24.3
      mSv), with the majority attributable solely to RNA (24.7 +/- 14.8 mSv, 72.6%).
      Actual ERD associated with RNA in this population differed significantly from the
      perception in surveyed cardiologists and oncologists; 70% of respondents believed
      that RNA typically accounted for 0% to 20% of overall radiation exposure from
      imaging; RNA actually accounted for more than 70% of ERD. In conclusion, RNA was
      used to monitor LVEF in most patients in this cohort during and after trastuzumab
      therapy. This significantly increased ERD and accounted for a greater proportion
      of radiation than that perceived by surveyed physicians. ERD should be taken into
      account when choosing a method of LVEF surveillance. Alternative techniques that
      do not use radiation should be strongly considered. 

PMID- 27040574
TI  - Effect of Serum Fibrinogen, Total Stent Length, and Type of Acute Coronary
      Syndrome on 6-Month Major Adverse Cardiovascular Events and Bleeding After
      Percutaneous Coronary Intervention.
AB  - This study evaluated the relation between baseline fibrinogen and 6-month major
      adverse cardiovascular events (MACE) and bleeding after percutaneous coronary
      intervention (PCI). Three hundred eighty-seven subjects (65.6 +/- 16.1 years,
      69.5% men, 26.9% acute coronary syndrome [ACS]) who underwent PCI with baseline
      fibrinogen and platelet reactivity (VerifyNow P2Y12 assay, Accumetrics, San
      Diego, California) measured were enrolled. Fibrinogen (368.8 +/- 144.1 vs 316.8
      +/- 114.3 mg/dl; p = 0.001), total stent length (TSL; 44.5 +/- 25.0 vs 32.2 +/-
      20.1 mm; p <0.001), and ACS presentation (40.6% vs 23.9%; p = 0.005) were
      independently associated with 6-month MACE rates (17.8%: myocardial infarction
      9.8%, rehospitalization for ACS 3.6%, urgent revascularization 3.6%, stroke 0.5%,
      and death 0.3%). Measures of platelet reactivity were not associated with 6-month
      MACE. After multivariate analysis, fibrinogen >=280 mg/dl (odds ratio [OR] 2.60,
      95% CI 1.33 to 5.11, p = 0.005), TSL >=32 mm (OR 3.21, 95% CI 1.82 to 5.64, p
      <0.001), and ACS presentation (OR 2.58, 95% CI 1.45 to 4.61, p = 0.001) were
      associated with higher 6-month MACE. In 271 subjects receiving chronic P2Y12
      inhibitor therapy, 6-month Thrombolysis In Myocardial Infarction bleeding after
      PCI was 7.0%, but no difference in fibrinogen level (338.3 +/- 109.7 vs 324.3 +/-
      113.8 mg/dl, p = 0.60) stratified by Thrombolysis In Myocardial Infarction
      bleeding was observed. In conclusion, elevated serum fibrinogen, ACS
      presentation, and longer TSL are independently associated with higher 6-month
      MACE after PCI, whereas no association with on-thienopyridine platelet reactivity
      and 6-month MACE was observed. Post-PCI bleeding was not associated with lower
      fibrinogen level.

PMID- 27040575
TI  - Usefulness of Rotational Atherectomy in the Current Era.

PMID- 27040576
TI  - Prognostic Significance of Hyperuricemia in Patients With Acute Heart Failure.
AB  - Serum uric acid (UA) is associated with death and hospitalization in chronic
      heart failure (HF). However, UA in acute HF has not been well studied with
      respect to its relation to renal dysfunction and vascular congestion. We measured
      admission serum UA along with baseline variables in 281 patients with acute HF
      screened from the Loop Diuretics Administration and Acute Heart Failure (Diur-HF)
      trial. Hyperuricemia was defined as serum UA >7 mg/dl in men and >6 mg/dl in
      women. Chronic kidney disease (CKD) was defined as an estimated glomerular
      filtration rate <60 ml/min/1.73 m(2) before hospital admission. Death or HF
      hospitalization at 6 months was the primary outcome. The mean UA concentration
      was 6.4 +/- 2.5 mg/dl, and 121 patients (43.1%) were classified as hyperuricemic.
      UA values were significantly increased in patients with CKD compared to patients
      without CKD (6.8 +/- 2.7 vs 6.1 +/- 2.1 mg/dl; p = 0.02); however, UA was not
      associated with the development of acute kidney injury. Patients with
      hyperuricemia had greater degrees of pulmonary and systemic congestion than
      normouricemic patients (congestion score 3.5 vs 2.1, p <0.01). Hyperuricemia was
      associated with higher risk of death or HF rehospitalization (univariate hazard
      ratio 1.46 [1.02 to 2.10]; p = 0.04, multivariate hazard ratio 1.69 [1.16 to
      2.45]; p = 0.005). In conclusion, hospitalized patients with acute HF, elevated
      UA levels were associated with both CKD and pulmonary congestion. After
      controlling for potential confounders, hyperuricemia was associated with
      rehospitalization and death at 6 months. 

PMID- 27040577
TI  - Epidemiologic evaluation of multiple alternate microbial water quality monitoring
      indicators at three California beaches.
AB  - INTRODUCTION: Advances in molecular methods provide new opportunities for
      directly measuring pathogens or host-associated markers of fecal pollution
      instead of relying on fecal indicator bacteria (FIB) alone for beach water
      quality monitoring. Adoption of new indicators depends on identifying
      relationships between either the presence or concentration of the indicators and
      illness among swimmers. Here we present results from three epidemiologic studies
      in which a broad range of bacterial and viral indicators of fecal contamination
      were measured simultaneously by either culture or molecular methods along with
      Enterococcus to assess whether they provide better health risk prediction than
      current microbial indicators of recreational water quality. METHODS: We conducted
      prospective cohort studies at three California beaches -- Avalon Bay (Avalon),
      Doheny State Beach (Doheny), Surfrider State Beach (Malibu) -- during the summers
      of 2007, 2008 and 2009. The studies enrolled 10,785 swimmers across the beaches
      and recorded each swimmer's water exposure. Water and sand samples were collected
      several times per day at multiple locations at each beach and analyzed for up to
      41 target indicators using 67 different methodologies. Interviewers contacted
      participants by phone 10-14 days later and recorded symptoms of gastrointestinal
      illness occurring after their beach visit. Regression models were used to
      evaluate the association between water quality indicators and gastrointestinal
      illness among swimmers at each beach. RESULTS: F+ coliphage (measured using EPA
      Method 1602) exhibited a stronger association with GI illness than did EPA Method
      1600 at the two beaches where it was measured, while a molecular method, F+ RNA
      Coliphage Genotype II, was the only indicator significantly associated with GI
      illness at Malibu. MRSA, a known pathogen, had the strongest association with GI
      illness of any microbe measured at Avalon. There were two methods targeting human
      associated fecal anaerobic bacteria that were more strongly associated with GI
      illness than EPA Method 1600, but only at Avalon. No indicator combinations
      consistently had a higher odds ratio than EPA Method 1600, but one composite
      indicator, based on the number of pathogens detected at a beach, was
      significantly associated with gastrointestinal illness at both Avalon and Doheny
      when freshwater flow was high. DISCUSSION: While EPA Method1600 performed
      adequately at two beaches based on its consistency of association with
      gastrointestinal illness and the precision of its estimated associations, F+
      coliphage measured by EPA Method 1602 had a stronger association with GI illness
      under high risk conditions at the two beaches where it was measured. One
      indicator, F+ Coliphage Genotype II was the only indicator significantly
      associated with GI illness at Malibu. Several indicators, particularly those
      targeting human associated bacteria, exhibited relationships with GI illness that
      were equal to or greater than that of EPA Method 1600 at Avalon, which has a
      focused human fecal source. Our results suggest that site-specific conditions at
      each beach determine which indicator or indicators best predict GI illness.

PMID- 27040578
TI  - Corrigendum to "Determining the mechanisms for aerobic granulation from mixed
      seed of floccular and crushed granules in activated sludge wastewater treatment"
      [Water Res. 46 (2012) 761-771].

PMID- 27040579
TI  - Corrigendum to "Breakage and growth towards a stable aerobic granule size during
      the treatment of wastewater" [Water Res. 47 (2013) 5338-5349].

PMID- 27040580
TI  - Corrigendum to "Modeling the inactivation of ascaris eggs as a function of
      ammonia concentration and temperature" [Water Res. 83 (2015) 153-160].

PMID- 27040581
TI  - Milk fat globule membrane coating of large lipid droplets in the diet of young
      mice prevents body fat accumulation in adulthood.
AB  - Epidemiological studies have demonstrated protective effects of breast-feeding on
      childhood obesity. Differences between human milk and infant milk formula (IMF)
      in dietary lipid structure may contribute to this effect. In our mouse model,
      feeding a diet containing large lipid droplets coated with phospholipids (PL)
      (Nuturis(r); PL of milk fat globule membrane (MFGM) fraction origin) in early
      life protected against excessive body fat accumulation following a diet challenge
      in adult life. We now set out to determine the relevance of increased droplet
      size and/or MFGM lipid droplet coating to the observed anti-obesogenic effects in
      adult life. From day 16 to 42, male mouse pups were exposed to diets with small
      (S) or large (L) lipid droplets (0.3 v. 2.9 um average mode diameter,
      respectively), either without MFGM or with MFGM coating around the lipid droplet,
      resulting in four groups: S (control diet), L, Scoating and Lcoating (Nuturis(r)
      IMF diet). Mice were subsequently challenged with a Western-style diet until
      dissection at postnatal day 98. A non-challenged group served as reference (REF).
      We repeatedly determined body composition between postnatal day 42 and 98. At day
      98 plasma and gene expression measurements were performed. Only the Nuturis(r)
      IMF diet (Lcoating) in early life containing MFGM-coated large lipid droplets
      reduced body fat mass to a level comparable with the REF group. These data
      support the notion that the structural aspects of lipids in human milk, for
      example, both lipid droplet size as well as the MFGM coating, may contribute to
      its reported protective effect against obesity in later life.

PMID- 27040583
TI  - Facial Nerve and Parotid Gland Anatomy.
AB  - This article provides an overview of important anatomic and functional anatomy
      associated with the parotid gland and facial nerve for the practicing
      otolaryngologist, head and neck surgeon, facial plastic surgeon, and plastic
      surgeon. The discussion includes the important anatomic relationships and
      physiology related to the parotid gland and salivary production. A comprehensive
      description of the path of facial nerve, its branches, and important anatomic
      landmarks also are provided. 

PMID- 27040582
TI  - Update on the spider and the fly: An extended commentary on "Oxidized LDL induced
      extracellular trap formation in human neutrophils via TLR-PKC-IRAK-MAPK and NADPH
      Oxidase activation".

PMID- 27040584
TI  - Benign Parotid Tumors.
AB  - This article reviews the epidemiology, embryology, risk factors, clinical
      presentation, diagnostic work-up, and basic management principles for the more
      common benign parotid neoplasms. The various histopathologies are also discussed
      and summarized. 

PMID- 27040586
TI  - Parotidectomy for Benign Parotid Tumors.
AB  - Parotidectomy for benign tumors is undergoing constant evolution. The potential
      for recurrence and malignant transformation of pleomorphic adenomas creates
      complexities that have forced head and neck surgeons to undertake more
      comprehensive parotid surgery with facial nerve dissection. This approach carries
      inherent morbidities, including facial nerve injury, Frey syndrome, and facial
      asymmetry, that have to be addressed. Extracapsular dissection is compared with
      conventional superficial parotidectomy; surgical histologic findings are
      discussed as well as outcome data. More novel approaches are discussed as well.
      This article provides a systematic approach to benign parotid tumor surgery. 

PMID- 27040585
TI  - Diagnosis and Management of Malignant Salivary Gland Tumors of the Parotid Gland.
AB  - Malignant parotid tumors are heterogeneous and diverse. Accurate diagnosis
      requires a pathologist familiar with the various histologic subtypes,
      immunohistochemistry stains, and common translocations. Clinical course varies
      according to tumor subtype, ranging from indolent, slow-growing adenoid cystic
      carcinoma to rapidly progressive, possibly fatal, salivary ductal carcinoma.
      Histologic grade is important in prognosis and therapy. Surgery remains the
      mainstay of treatment when negative margins can be achieved. Radiation improves
      locoregional control of tumors with high-risk features. Chemotherapy for parotid
      tumors can be disappointing. Studies of new targeted therapies have not offered
      significant benefits. 

PMID- 27040587
TI  - Parotid Gland Tumors and the Facial Nerve.
AB  - Various types of parotid gland tumors are discussed from nonneoplastic to both
      benign and malignant neoplasms. The anatomic relationship of the facial nerve is
      discussed as it exits the stylomastoid foramen and courses through the parotid
      gland. The effect of certain tumors on facial nerve function is also
      characterized. Details on which types of parotid tumors are more likely to affect
      facial nerve function and different prognostic predictors of return to function
      are evaluated. In addition, the prognostic value of tumor size and histologic
      type of parotid tumor is included. 

PMID- 27040588
TI  - Microvascular Reconstruction of the Parotidectomy Defect.
AB  - Parotidectomy is a commonly performed procedure for both benign and malignant
      lesions. When a significant portion of the gland is resected and the lost tissue
      volume is not replaced, a disfiguring contour defect can result. This defect can
      be disfiguring and have a profound impact on quality of life. Large defects are
      best replaced with vascularized tissue to provide stable volume. 

PMID- 27040589
TI  - Periocular Reconstruction in Patients with Facial Paralysis.
AB  - Facial paralysis can result in serious ocular consequences. All patients with
      orbicularis oculi weakness in the setting of facial nerve injury should undergo a
      thorough ophthalmologic evaluation. The main goal of management in these patients
      is to protect the ocular surface and preserve visual function. Patients with
      expected recovery of facial nerve function may only require temporary and
      conservative measures to protect the ocular surface. Patients with prolonged or
      unlikely recovery of facial nerve function benefit from surgical rehabilitation
      of the periorbital complex. Current reconstructive procedures are most commonly
      intended to improve coverage of the eye but cannot restore blink. 

PMID- 27040590
TI  - Comprehensive Management of Parotid Disorders.

PMID- 27040591
TI  - Pulsed electrical stimulation benefits wound healing by activating skin
      fibroblasts through the TGFbeta1/ERK/NF-kappaB axis.
AB  - BACKGROUND: Dermal fibroblasts activated by conductive polymer-mediated
      electrical stimulation (ES) have shown myofibroblast characteristics that favor
      wound healing. However, the signaling pathway related to this phenotype switch
      remains unclear, and the in vivo survival of the electrically activated cells has
      never been studied. METHODS: Primary human skin fibroblasts were exposed to
      pulsed-ES mediated through polypyrrole (PPy) coated fabrics. The expression of
      alpha-smooth muscle actin (alpha-SMA) and the signaling pathways were
      investigated by ELISA, Western blot and specific inhibition test, and
      immunocytochemistry staining as well as qRT-PCR analysis. In vivo implantation
      was performed in a mouse model to clarify the cell fate or contractile phenotype
      maintenance following ES stimulation. RESULTS: We demonstrated the upregulation
      of TGFbeta1 and phosph-ERK, and the NF-kappaB nuclear enrichment in the ES
      activated cells. The ES-activated fibroblasts retained high level of alpha-smooth
      muscle actin expression even after prolonged subculture. Subcutaneous
      implantation for 15 days revealed more human myofibroblasts in the experimental
      groups. CONCLUSIONS: These findings demonstrate for the first time the
      involvement of the TGFbeta1/ERK/NF-kappaB signaling pathway in ES-activated
      fibroblasts. The ES induced phenotype switch proves stable in subculture and in
      animal, pointing potential application in wound healing. GENERAL SIGNIFICANCE:
      Reveal of how ES activates cells and the implication of ES activated cells in
      wound healing.

PMID- 27040592
TI  - Measuring and Modeling Organochlorine Pesticide Response to Activated Carbon
      Amendment in Tidal Sediment Mesocosms.
AB  - Activated carbon (AC) sediment amendment for hydrophobic organic contaminants
      (HOCs) is attracting increasing regulatory and industrial interest. However,
      mechanistic and well-vetted models are needed. Here, we conduct an 18 month field
      mesocosm trial at a site containing dichlorodiphenyltrichloroethane (DDT) and
      chlordane. Different AC applications were applied and, for the first time, a
      recently published mass transfer model was field tested under varying
      experimental conditions. AC treatment was effective in reducing DDT and chlordane
      concentration in polyethylene (PE) samplers, and contaminant extractability by
      Arenicola brasiliensis digestive fluids. A substantial AC particle size effect
      was observed. For example, chlordane concentration in PE was reduced by 93% 6
      months post-treatment in the powdered AC (PAC) mesocosm, compared with 71% in the
      granular AC (GAC) mesocosm. Extractability of sediment-associated DDT and
      chlordane by A. brasiliensis digestive fluids was reduced by at least a factor of
      10 in all AC treatments. The model reproduced the relative effects of varying
      experimental conditions (particle size, dose, mixing time) on concentrations in
      polyethylene passive samplers well, in most cases within 25% of experimental
      observations. Although uncertainties such as the effect of long-term AC fouling
      by organic matter remain, the study findings support the use of the model to
      assess long-term implications of AC amendment.

PMID- 27040593
TI  - Potential exposure to Zika virus for foreign tourists during the 2016 Carnival
      and Olympic Games in Rio de Janeiro, Brazil.

PMID- 27040594
TI  - Randomized multicentre trial comparing external and internal pancreatic stenting
      during pancreaticoduodenectomy.
AB  - BACKGROUND: There is no consensus on the best method of preventing postoperative
      pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre,
      parallel group, randomized equivalence trial investigated the effect of two ways
      of pancreatic stenting after PD on the rate of POPF. METHODS: Patients undergoing
      elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy
      were enrolled from four tertiary referral hospitals. Randomization was stratified
      according to surgeon with a 1 : 1 allocation ratio to avoid any related technical
      factors. The primary endpoint was clinically relevant POPF rate. Secondary
      endpoints were nutritional index, remnant pancreatic volume, long-term
      complications and quality of life 2 years after PD. RESULTS: A total of 328
      patients were randomized to the external (164 patients) or internal (164) stent
      group between August 2010 and January 2014. The rates of clinically relevant POPF
      were 24.4 per cent in the external and 18.9 per cent in the internal stent group
      (risk difference 5.5 per cent). As the 90 per cent confidence interval (-2.0 to
      13.0 per cent) did not fall within the predefined equivalence limits (-10 to 10
      per cent), the clinically relevant POPF rates in the two groups were not
      equivalent. Similar results were observed for patients with soft pancreatic
      texture and high fistula risk score. Other postoperative outcomes were comparable
      between the two groups. Five stent-related complications occurred in the external
      stent group. Multivariable analysis revealed that soft pancreatic texture, non
      pancreatic disease and high body mass index (23.3 kg/m2 or above) predicted
      clinically relevant POPF. CONCLUSION: External stenting after PD was associated
      with a higher rate of clinically relevant POPF than internal stenting.
      Registration number: NCT01023594 (https://www.clinicaltrials.gov).

PMID- 27040595
TI  - The mental health of civilians displaced by armed conflict: an ecological model
      of refugee distress.
AB  - Early research on the mental health of civilians displaced by armed conflict
      focused primarily on the direct effects of exposure to war-related violence and
      loss. Largely overlooked in this war exposure model were the powerful effects of
      ongoing stressors related to the experience of displacement itself. An ecological
      model of refugee distress is proposed, drawing on research demonstrating that
      mental health among refugees and asylum seekers stems not only from prior war
      exposure, but also from a host of ongoing stressors in their social ecology, or
      displacement-related stressors. Implications of this model for addressing the
      mental health and psychosocial needs of refugees and other displaced populations
      are considered.

PMID- 27040597
TI  - Corrigendum.

PMID- 27040596
TI  - Hairpin Furans and Giant Biaryls.
AB  - The thermal reaction of two cyclopentadienones with 5,5'-binaphthoquinone or 6,6'
      dimethoxy-5,5'-binaphthoquinone in refluxing nitrobenzene (210  degrees C) gives,
      in a single synthetic step that includes two Diels-Alder additions, two
      decarbonylations, and two dehydrogenations, giant biaryl bisquinones (compounds
      13, 14, 15, 18, and 21). However, when two cyclopentadienones react with 6,6'
      dimethoxy-5,5'-binaphthoquinone in nitrobenzene at higher temperatures (250-260 
      degrees C), the resulting products are molecular ribbons composed of two twisted
      aromatic systems fused to a heteropentahelicene (19, 20, and 22). These molecules
      are representatives of a new class of chiral polycyclic aromatic compounds, the
      "hairpin furans". Interestingly, reheating a dimethoxy-substituted giant biaryl
      (e.g., 21) in nitrobenzene at 260  degrees C does not yield the corresponding
      hairpin furan (22), and mechanistic studies indicate that some intermediate or
      byproduct of the synthesis of the giant biaryls is a reagent or catalyst
      necessary for the conversion of the dimethoxybiaryl to the furan.

PMID- 27040598
TI  - Antibiotics and antiseptics for pressure ulcers.
AB  - BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and
      pressure injuries, are localised areas of injury to the skin or the underlying
      tissue, or both. A range of treatments with antimicrobial properties, including
      impregnated dressings, are widely used in the treatment of pressure ulcers. A
      clear and current overview is required to facilitate decision making regarding
      use of antiseptic or antibiotic therapies in the treatment of pressure ulcers.
      This review is one of a suite of Cochrane reviews investigating the use of
      antiseptics and antibiotics in different types of wounds. It also forms part of a
      suite of reviews investigating the use of different types of dressings and
      topical treatments in the treatment of pressure ulcers. OBJECTIVES: To assess the
      effects of systemic and topical antibiotics, and topical antiseptics on the
      healing of infected and uninfected pressure ulcers being treated in any clinical
      setting. SEARCH METHODS: In October 2015 we searched: the Cochrane Wounds
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other
      Non-Indexed Citations), Ovid EMBASE, and EBSCO CINAHL Plus. We also searched
      three clinical trials registries and the references of included studies and
      relevant systematic reviews. There were no restrictions based on language or date
      of publication or study setting. SELECTION CRITERIA: Randomised controlled trials
      which enrolled adults with pressure ulcers of stage II or above were included in
      the review. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed study selection, risk of bias assessment and data extraction. MAIN
      RESULTS: We included 12 trials (576 participants); 11 had two arms and one had
      three arms. All assessed topical agents, none looked at systemic antibiotics. The
      included trials assessed the following antimicrobial agents: povidone iodine,
      cadexomer iodine, gentian violet, lysozyme, silver dressings, honey, pine resin,
      polyhexanide, silver sulfadiazine, and nitrofurazone with ethoxy-diaminoacridine.
      Comparators included a range of other dressings and ointments without
      antimicrobial properties and alternative antimicrobials. Each comparison had only
      one trial, participant numbers were low and follow-up times short. The evidence
      varied from moderate to very low quality.Six trials reported the primary outcome
      of wound healing. All except one compared an antiseptic with a non-antimicrobial
      comparator. There was some moderate and low quality evidence that fewer ulcers
      may heal in the short term when treated with povidone iodine compared with non
      antimicrobial alternatives (protease-modulating dressings (risk ratio (RR) 0.78,
      95% confidence interval (CI) 0.62 to 0.98) and hydrogel (RR 0.64, 95% CI 0.43 to
      0.97)); and no clear difference between povidone iodine and a third non
      antimicrobial treatment (hydrocolloid) (low quality evidence). Pine resin salve
      may heal more pressure ulcers than hydrocolloid (RR 2.83, 95% CI 1.14 to 7.05)
      (low quality evidence). There is no clear difference between cadexomer iodine and
      standard care, and between honey a combined antiseptic and antibiotic treatment
      (very low quality evidence).Six trials reported adverse events (primary safety
      outcome). Four reported no adverse events; there was very low quality evidence
      from one showing no clear evidence of a difference between cadexomer iodine and
      standard care; in one trial it was not clear whether data were appropriately
      reported.There was limited reporting of secondary outcomes. The five trials that
      reported change in wound size as a continuous outcome did not report any clear
      evidence favouring any particular antiseptic/anti-microbial treatments. For
      bacterial resistance, one trial found some evidence of more MRSA eradication in
      participants with ulcer treated with a polyhexanide dressing compared with a
      polyhexanide swab (RR 1.48, 95% CI 1.02 to 2.13); patients in the dressing group
      also reported less pain (MD -2.03, 95% CI -2.66 to -1.40). There was no clear
      evidence of a difference between interventions in infection resolution in three
      other comparisons. Evidence for secondary outcomes varied from moderate to very
      low quality; where no GRADE assessment was possible we identified substantial
      limitations which an assessment would have taken into account. AUTHORS'
      CONCLUSIONS: The relative effects of systemic and topical antimicrobial
      treatments on pressure ulcers are not clear. Where differences in wound healing
      were found, these sometimes favoured the comparator treatment without
      antimicrobial properties. The trials are small, clinically heterogenous,
      generally of short duration, and at high or unclear risk of bias. The quality of
      the evidence ranges from moderate to very low; evidence on all comparisons was
      subject to some limitations.

PMID- 27040599
TI  - Coronary Bypass--Survival Benefit in Heart Failure.

PMID- 27040601
TI  - Tuning band alignment by CdS layers using a SILAR method to enhance TiO2/CdS/CdSe
      quantum-dot solar-cell performance.
AB  - We report tuning band alignment by optimized CdS layers using a SILAR method to
      achieve the recorded best performance with about 6% PCE in TiO2/CdS/CdSe QDSSCs.
      Combining experimental and theoretical studies, we find that a better lattices
      match between CdS and TiO2 assists the growth of CdSe, and the combined effect of
      charge transfer and surface dipole moment at the TiO2/CdS/CdSe interface shifts
      the energy levels of TiO2 upward and increases Voc of the solar cells. More
      importantly, the band gap of CdS buffer layers is sensitive to the distortion
      induced by lattice mismatch and numbers of CdS layers. For example, the barrier
      for charge transfer disappears when there are more than 4 layers of CdS,
      facilitating the charge injection from CdSe to TiO2. 

PMID- 27040600
TI  - In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist
      molindone hydrochloride.
AB  - Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5
      receptor antagonist activity. As an integral component of its preclinical safety
      evaluation, molindone hydrochloride was evaluated in a series of in vitro and in
      vivo genetic toxicology assays. In the bacterial reverse gene mutation assays
      employing four Salmonella tester strains (TA98, TA100, TA1535, and TA1537) and
      the E. coli tester strain WP2uvrA, molindone hydrochloride was negative in all
      strains, except TA100, in which it induced a positive response (up to 3-fold) in
      the presence of rat liver S9. With human S9, a small (2-fold), but
      nonreproducible, increase in revertants was observed in TA100 at the highest
      concentration of molindone tested (5,000 ug/plate). The mutagenicity was
      completely abrogated by the addition of glutathione and UDP-glucuronic acid to
      rat liver S9, suggesting detoxification of the mutagenic metabolite(s) by Phase
      II conjugation reactions, pathways commonly operational in humans. Molindone
      hydrochloride did not induce chromosomal aberrations in human lymphocyte
      cultures, did not elicit a positive response in a rat bone marrow micronucleus
      test for clastogencity/aneugenicity, and did not give a positive response in the
      rat liver comet assay for DNA damage. Collectively, the weight of evidence from
      these studies, combined with a large margin of safety and efficient
      detoxification through Phase II conjugation supports the interpretation that
      molindone hydrochloride does not pose a genotoxic risk to humans at the
      anticipated clinical dose levels.

PMID- 27040602
TI  - How Informative Are Drug-Drug Interactions of Gene-Drug Interactions?
AB  - FDA recommendations to manage polymorphic CYP-mediated drug-drug interactions
      (DDIs) and gene-drug interactions (GDIs) are typically similar. However, DDIs may
      not always reliably predict GDIs because the victim drug may have multiple
      metabolic pathways and the perpetrator drug may affect multiple enzymes or
      transporters. Consequently, it is of great interest to both the pharmaceutical
      industry and regulatory agencies to determine if DDI studies can be leveraged to
      inform GDIs or vice versa for dose adjustment and labeling. The objective of this
      study was to investigate under what circumstances DDIs can be used to predict
      GDIs for prototypical CYP2C9, CYP2C19, and CYP2D6 substrates. We investigated
      model substrates for CYP2D6 (metoprolol, dextromethorphan, atomoxetine, and
      vortioxetine), CYP2C9 (warfarin, flurbiprofen, and celecoxib), and CYP2C19
      (omeprazole and clopidogrel). Data on drug exposure for poor metabolizers (GDI)
      and for DDIs mediated by strong/moderate inhibitors in extensive metabolizers
      were collected. The impact of DDIs and GDIs on drug exposure was compared using:
      (1) a descriptive and (2) a physiologically based pharmacokinetic convergence
      analysis. Results from both approaches indicate that information on DDIs can be
      used to reliably predict GDIs for CYP2D6 substrates. The situation is more
      complex for CYP2C9 and CYP2C19 substrates because dose of the inhibitor (CYP2C9)
      and potency of the inhibitor (CYP2C19) impact the extent to which perpetrator
      drugs phenotypically convert extensive metabolizers to poor(er) metabolizers.

PMID- 27040603
TI  - A reinforcement of the sutured microvascular anastomosis with fibrin glue
      application: A retrospective comparative study with the standard conventional
      technique.
AB  - PURPOSE: Although a reasonable number of studies report satisfactory results with
      fibrin glue application in microvascular anastomosis since 1977, its utilization
      in the clinical setting has being scant in the literature. The aim of this study
      was to report the cumulated experience with the fibrin glue in free flaps over a
      period of 10 years, comparing the survival rate with the standard sutured
      anastomosis. PATIENTS AND METHODS: From August 2001 through November 2014, 83
      consecutive free flaps were performed by a team of surgeons from two hospitals.
      About 56 flaps were performed in 56 patients using the fibrin glue augmented
      microvascular anastomosis and 27 flaps were performed in 27 patients using the
      conventional anastomosis technique. The decision on whether or not the fibrin
      glue should be used at the anastomoses was based on its availability and whose
      surgeon was performing the anastomoses. About approximately 60% of sutures
      stitches were used that would be used in a conventional anastomosis, when fibrin
      glue application was anticipated (ranging from 5 to 7 sutures in the arteries and
      5 to 8 in the veins). RESULTS: The overall survival rate of the flaps performed
      with fibrin glue application was 92.85%. In one case, a revision of the venous
      anastomosis was required due to early flap congestion. Four cases (7.14%) had
      failure of the first free flap and two of them were submitted to another free
      flap without fibrin glue application. In the flaps performed with the
      conventional anastomosis technique the survival rate was 92.59%. This difference
      was not statistically significant (P = 0.97). CONCLUSION: The application of
      fibrin glue in microvascular anastomoses did not increase the rate of flap loss
      and had a potential to reduce the number of sutures required to complete an
      anastomosis by its sealing effect. (c) 2016 Wiley Periodicals, Inc. Microsurgery
      37:218-221, 2017.

PMID- 27040605
TI  - Effect of prestroke antiplatelets use on first-ever ischaemic stroke severity and
      early outcome.
AB  - OBJECTIVES: We aimed to investigate whether prior use of antiplatelet agents (AP)
      may be associated with lower severity and improved short-term outcome of the
      first-ever acute ischaemic stroke. METHODS: This was a retrospective, case
      control study based on a prospective hospital stroke registry covering
      consecutive acute stroke patients admitted to a single stroke centre in highly
      urbanised area (Warsaw, Poland) between 1995 and 2013. Patients receiving oral
      anticoagulants were excluded from the analysis. Statistical analysis included
      multiple regression and logistic regression adjusted for age, sex, hypertension,
      atrial fibrillation, congestive heart failure, diabetes, coronary heart disease
      and history of myocardial infarction. RESULTS: During the study period, there
      were 3036 eligible patients, of whom 879 (29%) received AP before stroke onset.
      Patients from the AP group were older and more often burdened with stroke risk
      factors. There were no differences in baseline stroke severity, hospital
      mortality and proportion of patients alive and independent at discharge. However,
      AP turned out to be independently associated with lower NIHSS score on admission
      (beta = -0.045, p = 0.008) and increased odds for being alive and independent at
      discharge (odds ratio 1.36, 95% CI: 1.13-1.67) and decreased odds for in-hospital
      mortality (odds ratio 0.77, 95% CI: 0.59-0.99). CONCLUSIONS: Our findings provide
      further evidence supporting modest benefit of AP therapy on the course and
      outcome of first-ever ischaemic stroke. Further large studies are needed to
      confirm this effect.

PMID- 27040604
TI  - Impact of Forest Management on Species Richness: Global Meta-Analysis and
      Economic Trade-Offs.
AB  - Forests managed for timber have an important role to play in conserving global
      biodiversity. We evaluated the most common timber production systems worldwide in
      terms of their impact on local species richness by conducting a categorical meta
      analysis. We reviewed 287 published studies containing 1008 comparisons of
      species richness in managed and unmanaged forests and derived management, taxon,
      and continent specific effect sizes. We show that in terms of local species
      richness loss, forest management types can be ranked, from best to worse, as
      follows: selection and retention systems, reduced impact logging, conventional
      selective logging, clear-cutting, agroforestry, timber plantations, fuelwood
      plantations. Next, we calculated the economic profitability in terms of the net
      present value of timber harvesting from 10 hypothetical wood-producing Forest
      Management Units (FMU) from around the globe. The ranking of management types is
      altered when the species loss per unit profit generated from the FMU is
      considered. This is due to differences in yield, timber species prices, rotation
      cycle length and production costs. We thus conclude that it would be erroneous to
      dismiss or prioritize timber production regimes, based solely on their ranking of
      alpha diversity impacts. 

PMID- 27040606
TI  - Adding Perspective: Predicting Adolescent Sunscreen Use with an Extended Health
      Action Process Approach.
AB  - BACKGROUND: Diseases such as skin cancer often have a very long latency period.
      For adolescents, especially, it may be difficult to grasp that current risk
      behavior is related to future health outcomes. This study examines the role of
      health-related time perspective (i.e. the degree to which short-term outcomes are
      discounted over long-time health benefits) within the Health Action Process
      Approach (HAPA). More specifically, based on expectancy*value theory, we tested
      whether time perspective interacts with self-efficacy, the central variable in
      this approach. METHODS: A longitudinal study with three measurement points across
      one year assessed 156 high school students. Data were analyzed using structural
      equation models. RESULTS: While time perspective had no direct association with
      sunscreen use intentions, there was an interaction effect with self-efficacy; the
      shorter the time perspective, the smaller the association of self-efficacy with
      intention. Intention in turn predicted planning and sunscreen use at Time 3 (one
      year later). CONCLUSIONS: In order to maximise the impact of early onset measures
      for skin cancer prevention targeting the motivation for sunscreen use in
      adolescents, time perspective should be addressed in comprehensive sun protection
      interventions.

PMID- 27040607
TI  - Gray matter volume and white matter lesions in chronic kidney disease: exploring
      the association with depressive symptoms.
AB  - OBJECTIVE: Chronic kidney disease (CKD) is associated with structural brain
      damage and with a high prevalence of depression. We therefore investigated
      structural brain alterations in both gray and white matter in CKD patients,
      focusing on depression-related (frontal-subcortical) regions. METHOD: This cross
      sectional MRI study in 24 CKD patients and 24 age- and sex-matched controls first
      tested whether CKD was associated with regionally lower gray matter (GM) volumes
      and more severe white matter lesions (WMLs). In exploratory subanalyses, we
      examined whether differences were more pronounced in CKD patients with depressive
      symptoms. RESULTS: CKD patients showed lower global GM volume (P=.04) and more
      severe WMLs (P=.04) compared to controls. In addition, we found substantial
      clusters of lower GM in the bilateral orbitofrontal-cortex for CKD patients,
      which were however nonsignificant after proper multiple-comparison correction. In
      exploratory analyses for depressed CKD patients, reduced GM clusters were mainly
      detected within the frontal lobe. WML severity was unrelated to depression.
      CONCLUSION: CKD was characterized by differences in brain structure. Although
      subthreshold, lower GM volumes were observed in depression-related brain areas
      and were more pronounced for depressed patients. There is a need for replication
      in larger and longitudinal studies to investigate whether WMLs and regional GM
      reductions may render CKD patients more susceptible for depression.

PMID- 27040608
TI  - In this April issue.

PMID- 27040611
TI  - Multiple Scrotal Ulcers in an Infant Due to a Traditional Child Care Practice:
      Salting.
AB  - Application of salt to the newborn's skin is a common traditional child care
      custom in Turkey. We present an infant with multiple ulcerating scrotal lesions
      due to prolonged salt exposure in the diaper area. Scrotal ulcers associated with
      salting have not been described previously. 

PMID- 27040612
TI  - Ant aggregations self-heal to compensate for the Ringelmann effect.
AB  - Fire ants, Solenopsis invicta, link their bodies together to form structures such
      as rafts, bivouacs and bridges. Such structures are in danger of being damaged by
      natural disturbances such as passing water currents. In this combined
      experimental and theoretical study, we investigate the self-healing of ant
      assemblages. We press two ant aggregations together and measure the forces to
      pull them apart. As the group size increases, the contribution of each ant
      decreases. This phenomenon, known as the Ringelmann effect, or social loafing,
      has previously been shown for cattle and humans. In this study, we show that it
      is a challenge for ants as well. We rationalize this effect with an agent-based
      simulation which exhibits the Ringelmann effect of ants that periodically make
      and break links with each other, but grip with higher probability if the ants are
      stretched. Over time, ants compensate for the Ringelmann effect by building more
      links. We use a mathematical model to show that the rate of new links is
      proportional to the number of free ants in the cluster. The principles found here
      may inspire new directions in self-healing and active materials.

PMID- 27040613
TI  - Identification of the novel HLA-A*01:200 allele by sequence-based typing in a
      Croatian individual.
AB  - The new allele HLA-A*01:200 differs from A*01:12 by four nucleotide substitutions
      in exon 3. 

PMID- 27040614
TI  - Dynamics and spectroscopy of CH2OO excited electronic states.
AB  - The excited states of the Criegee intermediate CH2OO are studied in molecular
      dynamics simulations using directly potentials from multi-reference perturbation
      theory (MR-PT2). The photoexcitation of the species is simulated, and
      trajectories are propagated in time on the excited state. Some of the
      photoexcitation events lead to direct fragmentation of the molecule, but other
      trajectories describe at least several vibrations in the excited state, that may
      terminate by relaxation to the ground electronic state. Limits on the role of non
      adiabatic contributions to the process are estimated by two different
      simulations, one that forces surface-hopping at potential crossings, and another
      that ignores surface hopping altogether. The effect of non-adiabatic transitions
      is found to be small. Spectroscopic implications and consequences for the
      interpretation of experimental results are discussed. 

PMID- 27040615
TI  - Trypsin inhibitor from Leucaena leucocephala seeds delays and disrupts the
      development of Aedes aegypti, a multiple-disease vector.
AB  - BACKGROUND: Nowadays, the Aedes aegypti mosquito represents a serious public
      health issue in view of the large outbreaks of the arboviral diseases zika,
      dengue, chikungunya and yellow fever. This holometabolous insect has midgut
      digestive enzymes that are trypsin- and chymotrypsin-like proteins. Protease
      inhibitors are able to bind to proteolytic enzymes and promote a blockage in
      digestion and nutrition, leading to death. Thus, we investigated the effect of
      trypsin inhibitor of Leucaena leucocephala (LTI) seeds on egg hatching, larval
      development and digestive midgut proteases. RESULTS: LTI was obtained by
      trichloroacetic acid precipitation followed by a single chromatography step on
      anhydrous trypsin sepharose. Polyacrylamide gel electrophoresis in the presence
      of sodium dodecyl sulphate showed a single protein band with a molecular mass
      close to 20 kDa. After exposure of Ae. aegypti eggs to LTI (0.3 mg mL-1 ), egg
      hatching was reduced (50%). LTI did not show acute toxicity on newly hatched
      larvae incubated under the same conditions, but after 10 days of exposure a high
      mortality rate (86%) was observed and the surviving larvae had a 25% delay in
      development. LTI was able to inhibit in vitro the midgut enzymatic activity
      (70%), and when larvae were incubated with LTI solution we observed an inhibition
      of 56%. CONCLUSIONS: LTI is a promising new tool to control critical points of
      Ae. aegypti development. (c) 2016 Society of Chemical Industry.

PMID- 27040616
TI  - An ancient and conserved function for Armadillo-related proteins in the control
      of spore and seed germination by abscisic acid.
AB  - Armadillo-related proteins regulate development throughout eukaryotic kingdoms.
      In the flowering plant Arabidopsis thaliana, Armadillo-related ARABIDILLO
      proteins promote multicellular root branching. ARABIDILLO homologues exist
      throughout land plants, including early-diverging species lacking true roots,
      suggesting that early-evolving ARABIDILLOs had additional biological roles. Here
      we investigated, using molecular genetics, the conservation and diversification
      of ARABIDILLO protein function in plants separated by c. 450 million years of
      evolution. We demonstrate that ARABIDILLO homologues in the moss Physcomitrella
      patens regulate a previously undiscovered inhibitory effect of abscisic acid
      (ABA) on spore germination. Furthermore, we show that A. thaliana ARABIDILLOs
      function similarly during seed germination. Early-diverging ARABIDILLO homologues
      from both P. patens and the lycophyte Selaginella moellendorffii can substitute
      for ARABIDILLO function during A. thaliana root development and seed germination.
      We conclude that (1) ABA was co-opted early in plant evolution to regulate
      functionally analogous processes in spore- and seed-producing plants and (2)
      plant ARABIDILLO germination functions were co-opted early into both gametophyte
      and sporophyte, with a specific rooting function evolving later in the land plant
      lineage.

PMID- 27040618
TI  - Host and parasite thermal acclimation responses depend on the stage of infection.
AB  - Global climate change is expected to alter patterns of temperature variability,
      which could influence species interactions including parasitism. Species
      interactions can be difficult to predict in variable-temperature environments
      because of thermal acclimation responses, i.e. physiological changes that allow
      organisms to adjust to a new temperature following a temperature shift. The goal
      of this study was to determine how thermal acclimation influences host resistance
      to infection and to test for parasite acclimation responses, which might differ
      from host responses in important ways. We tested predictions of three, non
      mutually exclusive hypotheses regarding thermal acclimation effects on infection
      of green frog tadpoles (Lithobates clamitans) by the trematode parasite Ribeiroia
      ondatrae with fully replicated controlled-temperature experiments. Trematodes or
      tadpoles were independently acclimated to a range of 'acclimation temperatures'
      prior to shifting them to new 'performance temperatures' for experimental
      infections. Trematodes that were acclimated to intermediate temperatures (19-22 
      degrees C) had greater encystment success across temperatures than either cold-
      or warm-acclimated trematodes. However, host acclimation responses varied
      depending on the stage of infection (encystment vs. clearance): warm- (22-28 
      degrees C) and cold-acclimated (13-19  degrees C) tadpoles had fewer parasites
      encyst at warm and cold performance temperatures, respectively, whereas
      intermediate-acclimated tadpoles (19-25  degrees C) cleared the greatest
      proportion of parasites in the week following exposure. These results suggest
      that tadpoles use different immune mechanisms to resist different stages of
      trematode infection, and that each set of mechanisms has unique responses to
      temperature variability. Our results highlight the importance of considering
      thermal responses of both parasites and hosts when predicting disease patterns in
      variable-temperature environments.

PMID- 27040617
TI  - Adoption of direct oral anticoagulants for stroke prevention in atrial
      fibrillation.
AB  - BACKGROUND: Direct oral anticoagulants (DOAC) are being increasingly utilised for
      stroke prevention in atrial fibrillation (AF) and atrial flutter. AIMS: To
      analyse the adoption and application of these drugs in a regional hospital
      inpatient cohort and compare with national prescribing data. METHODS: Digital
      medical records identified prescribed anticoagulants for patients admitted with
      AF and atrial flutter during 2013-2014. Analysis of patient demographics and
      stroke risk identified trends in prescribing DOAC versus warfarin. For broader
      comparison, data from the Pharmaceuticals Benefits Scheme were sourced to
      determine the nation-wide adoption of DOAC. RESULT: Of the 615 patients
      identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in
      the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P <
      0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and
      those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed
      to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P =
      0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular
      filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P
      = 0.006). Nationally, warfarin prescriptions are higher in total numbers but
      increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013,
      1 095 985 in 2014). CONCLUSION: DOAC prescribing grew rapidly from 2013 to 2014,
      regionally and nationally. Warfarin prescriptions have remained stable,
      indicating that more patients are being appropriately anticoagulated for AF who
      previously were not. DOAC were found to be prescribed to patients with lower CHA2
      DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates.
      Aspirin therapy remains over utilised in AF.

PMID- 27040619
TI  - Preliminary results for treatment of early stage breast cancer with endoscopic
      subcutaneous mastectomy combined with endoscopic sentinel lymph node biopsy in
      China.
AB  - BACKGROUND AND OBJECTIVES: To evaluate efficacy and aesthetic outcome for
      combined endoscopic subcutaneous mastectomy (E-SM) and endoscopic sentinel lymph
      node biopsy (E-SLNB) in early stage breast cancer patients. METHODS: Combined E
      SM+E-SLNB was compared to modified radical resection in a cohort of Chinese
      patients (n = 49) with stages I and II breast cancer. Patient satisfaction with
      the aesthetic results was assessed 1 year after surgery with a 5-item-by-4-step
      scoring system for evaluating cosmetic outcomes. RESULTS: All patients were alive
      1 year following surgery with no locoregional recurrence or distant metastases
      and without any critical complications. The average length of incision was less
      in patients receiving E-SM+E-SLNB (4.4 vs. 19.4 cm; P < 0.001), but time in
      surgery was longer (131.6 vs. 99.2 min; P = 0.024). After 1 year, nearly all E
      SM+E-SLNB patients rated satisfaction with their appearance as excellent or good
      (23/24; 95.8% vs. 19/25; 76.0%; P < 0.001), and exhibited less disturbance of
      sensory (P < 0.001) and motor function (P = 0.014) relative to modified radical
      resection. CONCLUSIONS: E-SM+E-SLNB provides significant aesthetic and functional
      advantages for patients with early stage breast cancer without compromising
      medical efficacy as assessed at 16 months postsurgery. J. Surg. Oncol.
      2016;113:616-620. (c) 2016 Wiley Periodicals, Inc.

PMID- 27040620
TI  - Chrysin Inhibits Lymphangiogenesis in Vitro.
AB  - The induction of lymphangiogenesis is an important process to promote cancer
      growth and cancer metastasis via the lymphatic system. Identifying the compounds
      that can prevent lymphangiogenesis for cancer therapy is urgently required.
      Chrysin, 5,7-dihydroxyflavone, a natural flavone extracted from Thai propolis,
      was used to investigate the effect on the lymphangiogenesis process of TR-LE, rat
      lymphatic endothelial cells. In this study, maximal nontoxic doses of chrysin on
      TR-LE cells were selected by performing a proliferation assay. The process of
      lymphangiogenesis in vitro was determined by cord formation assay, adhesion assay
      and migration assay. Chrysin at a nontoxic dose (25 MUM) significantly inhibited
      cord formation, cell adhesion and migration of TR-LE cells when compared with the
      control group. We also found that chrysin significantly induced vascular
      endothelial growth factor C (VEGF-C) mRNA expression and nitric oxide (NO)
      production in TR-LE cells which was involved in decreasing the cord formation of
      TR-LE cells. In conclusion, we report for the first time that chrysin inhibited
      the process of lymphangiogenesis in an in vitro model. This finding may prove to
      be a natural compound for anti-lymphangiogenesis that could be developed for use
      in cancer therapy.

PMID- 27040621
TI  - Novel Pyrazolo[3,4-b]pyridine Derivatives: Synthesis, Characterization,
      Antimicrobial and Antiproliferative Profile.
AB  - Three novel series of pyridine derivatives, namely Schiff's bases, 4
      thiazolidinones and azetidin-2-ones bearing pyrazolo[3,4-b]pyridine moiety, have
      been synthesized. The chemical structures of the synthesized compounds were
      characterized. The compounds were tested for their antimicrobial activity using
      the agar well diffusion and broth macrodilution methods. The compounds were also
      evaluated for their antiproliferative activity using the sulforhodamine B (SRB)
      assay. The majority of the tested compounds exhibited slight to high
      antimicrobial activity against the test microorganisms with minimum inhibitory
      concentrations (MICs) of 0.12-62.5 ug/mL when compared to that of 3 standard
      antimicrobial agents (Ampicillin, 0.007-0.03 ug/mL; Gentamicin; 0.015-0.24 ug/mL;
      and Amphotericin B, 0.03-0.98 ug/mL). Compound (7b) was found to be nearly as
      active as the standard antimicrobial drug Amphotericin B against Fusarium
      oxysporum fungal strain with MIC of 0.98 ug/mL. Some of the test compounds showed
      remarkable cytotoxic activities against Hep G2 (hepatocellular carcinoma) cells
      (IC50=0.0158-71.3 uM) in comparison to the standard anticancer drug doxorubicin
      (IC50=0.008 uM). Among the compounds tested, (5), (6a), (6b), (7b), and (10)
      exhibited antiproliferative potency (IC50=0.0001-0.0211 uM) that was found to be
      better than that of doxorubicin (IC50=0.099 uM) against MCF7 (breast
      adenocarcinoma) cells. In particular, (7b) displayed the highest significant
      antiproliferative efficacy against both Hep G2 and MCF7 cell lines showing IC50
      values of 0.0158 uM and 0.0001 uM, respectively. Our findings suggest that the
      synthesized compounds may be promising candidates as novel antimicrobial and
      antiproliferative agents.

PMID- 27040622
TI  - Molecular Analysis of Terminalia spp. Distributed in Thailand and Authentication
      of Crude Drugs from Terminalia Plants.
AB  - Terminalia, a large genus of Combretaceae, is distributed in Tropical Asia,
      Africa, and America. Some Terminalia plants are used in folk medicine because
      they possess powerful medicinal properties. Dried fruits of Terminalia bellirica
      and Terminalia chebula are used as the main ingredient in Triphala, a famous
      polyherbal formulation in Ayurvedic medicine and Thai folk medicine, because of
      their laxative, detoxifying, and rejuvenating effects. To clarify the
      phylogenetic relationships of medicinal Terminalia species (T. bellirica, T.
      chebula, and T. catappa) and authenticate their crude drugs, "Samo" and Triphala,
      nucleotide sequencing alignments in the internal transcribed spacer one-two (ITS
      1-2) regions of Terminalia plants collected in Thailand were performed. The
      amplified fragments of Terminalia species were approximately 800 bp in length. To
      compare these sequences and DDBJ registered data, a molecular phylogenetic tree
      was constructed. Phylogenetic analysis clearly separated the sequences into two
      groups: Asian Terminalia and African Terminalia with some exceptions. In the
      analyzed sequences, the length of the ITS1-5.8S-ITS2 region was 674 bp in T.
      chebula, and 677 bp in T. bellirica and T. catappa. Eighty-one single nucleotide
      polymorphisms (SNPs) and nine insertion-deletions (indels) were observed, and the
      nucleotide sequences of this region showed species-specific sequences. Based on
      these differences, polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) were
      applied to identify medicinal Terminalia species. Moreover, the ARMS method was
      chosen for fingerprinting analysis of Samo crude drugs and Triphala formulations
      because it was a fast, cost-effective, and reproducible approach.

PMID- 27040623
TI  - Design, Synthesis, and Molecular Docking Studies of a Conjugated Thiadiazole
      Thiourea Scaffold as Antituberculosis Agents.
AB  - In view of the emergence and frequency of multidrug-resistant and extensively
      drug-resistant tuberculosis and consequences of acquired resistance to clinically
      used drugs, we undertook the design and synthesis of novel prototypes that
      possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole
      in a single molecular backbone. Three compounds from our series were
      distinguished from the others by their promising activity profiles against
      Mycobacterium tuberculosis strain H37Rv. Compounds 11 and 19 were the most active
      representatives with minimum inhibitory concentration (MIC) values of 10.96 and
      11.48 uM, respectively. Compound 15 was shown to inhibit M. tuberculosis strain
      H37Rv with an MIC value of 17.81 uM. Cytotoxicity results in the Vero cell line
      showed that these three derivatives had selectivity indices between 1.8 and 8.7.
      In order to rationalize the biological results of our compounds, molecular
      docking studies with the enoyl acyl carrier protein reductase (InhA) of M.
      tuberculosis were performed and compounds 11, 15, and 19 were found to have good
      docking scores in the range of -7.12 to -7.83 kcal/mol.

PMID- 27040624
TI  - Clinical Assessment of Postoperative Anemia Associated with Edoxaban in Patients
      Undergoing Total Knee Arthroplasty Compared to Fondaparinux.
AB  - Edoxaban, an oral direct factor Xa inhibitor, was developed and approved for
      anticoagulant thromboprophylaxis after total knee arthroplasty (TKA). We
      retrospectively investigated the postoperative anemia by oral administration of
      edoxaban 30 mg compared with fondaparinux 2.5 mg in TKA patients. Two hundred
      twenty nine patients who underwent TKA in National Hospital Organization Okayama
      Medical Center from July 2010 to June 2012 were divided into two groups; pre and
      post approval of edoxaban: fondaparinux-group (F-group) and edoxaban-group (E
      group). As the primary endpoint, the frequency of postoperative anemia was
      evaluated. Blood coagulation values and relations between these parameters and
      postoperative anemia were also investigated. The frequency of postoperative
      anemia was significantly higher in E-group than F-group patients (52.7% vs.
      37.8%; p<0.05). Hemoglobin (Hgb) levels were decreased with the peak at
      postoperative day (POD) 3 in both groups, and the change of Hgb values from POD1
      (DeltaHgb) was significantly increased in the E-group (p=0.04). At each POD,
      prothrombin time (PT) and international normalized ratio of PT (PT-INR) prolonged
      from the preoperative day in E-group were significantly higher than F-group.
      Additionally, PT and PT-INR in the E-group at POD3 were significantly prolonged
      in patients with postoperative anemia and the sensitivity of cut-off values to
      predict postoperative anemia was superior to the activated partial thromboplastin
      time (APTT). Thus, as the frequency of postoperative anemia tended to be higher
      in E-group, edoxaban 30 mg might require vigilance, and prolonged PT and PT-INR
      could potentially predict edoxaban-associated postoperative anemia after TKA. 

PMID- 27040625
TI  - Skin Permeation of Testosterone from Viscoelastic Lecithin Reverse Wormlike
      Micellar Solution.
AB  - We evaluated testosterone-containing lecithin reverse wormlike micelles (reverse
      worms) composed of a polar substance/lecithin/isopropyl myristate for transdermal
      application. Water, D-ribose, or tetraglycerol were used as the polar substance
      and were key ingredients for forming the reverse worms. Using the reverse worms,
      1 wt% of testosterone could be stably solubilized. When using D-ribose as polar
      substance, the maximum zero-shear viscosity of the reverse worms solution was
      higher than that of systems using water or tetraglycerol as the polar substance.
      The mechanism of skin permeation of testosterone from reverse worms solution was
      elucidated using skin permeation experiments with hairless mouse skin. When the
      structure of the reverse worms transitioned to lamellar liquid crystals at the
      skin/formulation interface, testosterone became supersaturated in the
      formulations. The structural transition occurred in systems using water or D
      ribose as the polar substance, increasing the flux of testosterone. The flux of
      testosterone from reverse worms solution thus depends on the type of polar
      substance used.

PMID- 27040626
TI  - Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus
      (hRSV) Infection.
AB  - Human respiratory syncytial virus (hRSV) is the most common cause of
      bronchiolitis and pneumonia in infants. The lack of proper prophylactics and
      therapeutics for controlling hRSV infection has been of great concern worldwide.
      Xylitol is a well-known sugar substitute and its effect against bacteria in the
      oral cavity is well known. However, little is known of its effect on viral
      infections. In this study, the effect of dietary xylitol on hRSV infection was
      investigated in a mouse model for the first time. Mice received xylitol for 14 d
      prior to virus challenge and for a further 3 d post challenge. Significantly
      larger reductions in lung virus titers were observed in the mice receiving
      xylitol than in the controls receiving phosphate-buffered saline (PBS). In
      addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect
      inflammatory status, were recruited in the mice receiving xylitol. These results
      indicate that dietary xylitol can ameliorate hRSV infections and reduce
      inflammation-associated immune responses to hRSV infection. 

PMID- 27040627
TI  - A Dual Readout Assay Based on Fluorescence Polarization and Time-Resolved
      Fluorescence Resonance Energy Transfer to Screen for RSK1 Inhibitors.
AB  - A dual readout assay based on fluorescence polarization (FP) and time-resolved
      fluorescence resonance energy transfer (TR-FRET) exhibits many advantages over
      single assay technology in terms of screening quality and efficiency. In this
      study, we developed a dual readout assay combining FP and TR-FRET to identify
      ribosomal S6 kinase 1 (RSK1) inhibitors. This dual readout assay can monitor both
      FP and TR-FRET signals from a single RSK1 kinase reaction by using the
      immobilized metal affinity for phosphochemical (IMAP)-based assay. The Z' value
      and signal to background (S/B) ratio were 0.85 and 4.0 using FP, and 0.79 and
      10.6 using TR-FRET, which led to performance of a pilot library screening against
      the drug repositioning set consisting of 2320 compounds with a reasonable
      reproducibility. From this screening, we identified 16 compounds showing greater
      than 50% inhibition against RSK1 for both FP and TR-FRET; 6 compounds with
      greater than 50% inhibition only for FP; and 4 compounds with greater than 50%
      inhibition only for TR-FRET. In a cell-based functional assay to validate the hit
      compounds, 10 compounds identified only in a single assay had little effect on
      the RSK-mediated phosphorylation of liver kinase B1, whereas 5 compounds showing
      greater than 80% inhibition for both FP and TR-FRET reduced the phosphorylation
      of liver kinase B1. These results demonstrate that the dual readout assay can be
      used to identify hit compounds by subsequently monitoring both FP and TR-FRET
      signals from one RSK1 reaction. 

PMID- 27040628
TI  - The Responses of Pulmonary and Systemic Circulation and Airway to Allergic
      Mediators in Anesthetized Rats.
AB  - Lung allergic diseases sometimes accompany pulmonary vaso- and broncho
      constriction. Rats are currently used for the experimental study of lung
      allergies. However, their hemodynamic mechanisms are not fully understood.
      Therefore the effects of allergic mediators were determined systematically in
      vivo in rats in terms of pulmonary vascular resistance (PVR), airway pressure
      (AWP) and total peripheral resistance (TPR). We directly measured pulmonary
      arterial pressure, left atrial pressure, systemic arterial pressure, central
      venous pressure and aortic blood flow to determine PVR and TPR, as well as AWP,
      following injections of platelet-activating factor (PAF), histamine, serotonin,
      leukotriene (LT) C4, and prostaglandin (PG) D2 in anesthetized open-chest
      artificially ventilated Sprague-Dawley (SD) rats. PVR was dose-dependently
      increased by consecutive administration of PAF, LTC4, and PGD2, with the maximal
      responsiveness being PAF>LTC4>PGD2. However, neither histamine nor serotonin
      changed PVR. TPR was decreased by all agents except LTC4 which actually increased
      it. PAF and serotonin, but not the other agents, increased AWP. In conclusion,
      allergic mediators exert non-uniform actions on pulmonary and systemic
      circulation and airways in anesthetized SD rats: PAF, LTC4 and PGD2, but not
      histamine or serotonin, caused substantial pulmonary vasoconstriction; LTC4
      yielded systemic vasoconstriction, while the others caused systemic
      vasodilatation; only two mediators, PAF and serotonin, induce airway
      constriction. 

PMID- 27040629
TI  - Expression of Vesicular Nucleotide Transporter in the Mouse Retina.
AB  - Vesicular nucleotide transporter (VNUT) is a membrane protein that is responsible
      for vesicular storage and subsequent vesicular release of nucleotides, such as
      ATP, and plays an essential role in purinergic chemical transmission. In the
      present study, we investigated whether VNUT is present in the rodent retina to
      define the site(s) of vesicular ATP release. In the mouse retina, reverse
      transcription polymerase chain reaction (RT-PCR) and immunological analyses using
      specific anti-VNUT antibodies indicated that VNUT is expressed as a polypeptide
      with an apparent molecular mass of 59 kDa. VNUT is widely distributed throughout
      the inner and outer retinal layers, particularly in the outer segment of
      photoreceptors, outer plexiform layer, inner plexiform layer, and ganglion cell
      layer. VNUT is colocalized with vesicular glutamate transporter 1 and
      synaptophysin in photoreceptor cells, while it is colocalized with vesicular
      gamma-aminobutyric acid (GABA) transporter in amacrine cells and bipolar cells.
      VNUT is also present in astrocytes and Muller cells. The retina from VNUT
      knockout (VNUT(-/-)) mice showed the loss of VNUT immunoreactivity. The retinal
      membrane fraction took up radiolabeled ATP in diisothiocyanate stilbene
      disulfonic acid (DIDS)-, an inhibitor of VNUT, and bafilomycin A1-, a vacuolar
      adenosine triphosphatase (ATPase) inhibitor, in a sensitive manner, while
      membranes from VNUT(-/-) mice showed the loss of DIDS-sensitive ATP uptake. Taken
      together, these results indicate that functional VNUT is expressed in the rodent
      retina and suggest that ATP is released from photoreceptor cells, bipolar cells,
      amacrine cells, and astrocytes as well as Muller cells to initiate purinergic
      chemical transmission. 

PMID- 27040630
TI  - Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in
      Rats.
AB  - As one of the adverse effects of oxaliplatin, a key agent in colon cancer
      chemotherapy, a taste disorder is a severe issue in a clinical situation because
      it decreases the quality of life of patients. However, there is little
      information on the mechanism underlying the oxaliplatin-induced taste disorder.
      Here, we examined the molecular and behavioral characteristics of the oxaliplatin
      induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to
      Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and
      protein of taste receptors in circumvallate papillae (CP) were measured by real
      time quantitative polymerase chain reaction (PCR) and immunohistochemistry,
      respectively. Taste sensitivity was assessed by their behavioral change using a
      brief-access test. Morphological change of the taste buds in CP was evaluated by
      hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was
      counted by immunohistochemical analysis. Among taste receptors, the expression
      levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were
      increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief
      access test, the lick ratio was decreased in oxaliplatin-administered rats on day
      7 and the alteration was recovered to the control level on day 14. There was no
      detectable alteration in the morphology of taste buds, number of taste cells or
      plasma zinc level in oxaliplatin-administered rats. These results suggest that
      decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at
      least in part, to increased expression of T1R2, while these alterations are
      reversible. 

PMID- 27040631
TI  - Male Hypogonadism Causes Obesity Associated with Impairment of Hepatic
      Gluconeogenesis in Mice.
AB  - The steroid hormones synthesized by the male gonads play diverse roles in
      biological processes. Androgens, the primary hormones produced by the male
      gonads, are key regulators of fat homeostasis, hence androgen-deprivation
      therapies often induce obesity. However, the molecular mechanism by which male
      gonadal dysfunction leads to obesity remains unclear, because results from animal
      studies regarding fat accumulation in the context of gonadal defects do not
      reflect clinical findings. Here, we investigated the mechanism underlying the
      development of obesity in animals with male gonadal dysfunction by analyzing the
      long-term physiological changes in adult male mice with surgical castration. Nine
      weeks after surgery, white adipose tissue (WAT) mass was higher in the castrated
      (Cas) mice than in sham-operated (Sham) mice. In addition, castration induced
      hyperlipidemia and hyperglycemia. However, genes involved in lipid metabolism,
      including hormone-sensitive lipase, were unchanged in the adipose tissue of the
      Cas mice, despite the increase in WAT. In contrast, a hepatic gluconeogenesis
      gene, glucose-6-phosphatase, was significantly upregulated in the Cas mice than
      in Sham mice. Our findings suggest that long-term hypogonadism in mice mimics the
      effects in humans, and a potential molecular basis for the induction of obesity
      in this model is impairment of hepatic gluconeogenesis. 

PMID- 27040632
TI  - Deer Bone Oil Extract Suppresses Lipopolysaccharide-Induced Inflammatory
      Responses in RAW264.7 Cells.
AB  - The aim of this study was to investigate the effect of deer bone oil extract
      (DBOE) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7
      cells. DBOE was fractionated by liquid-liquid extraction to obtain two fractions:
      methanol fraction (DBO-M) and hexane fraction (DBO-H). TLC showed that DBO-M had
      relatively more hydrophilic lipid complexes, including unsaturated fatty acids,
      than DBOE and DBO-H. The relative compositions of tetradecenoyl carnitine, alpha
      linoleic acid, and palmitoleic acid increased in the DBO-M fraction by 61, 38,
      and 32%, respectively, compared with DBOE. The concentration of sugar moieties
      was 3-fold higher in the DBO-M fraction than DBOE and DBO-H. DBO-M significantly
      decreased LPS-induced nitric oxide (NO) production in RAW264.7 cells in a dose
      dependent manner. This DBO-M-mediated decrease in NO production was due to
      downregulation of mRNA and protein levels of inducible nitric oxide synthase
      (iNOS). In addition, mRNA expression of pro-inflammatory mediators, such as
      cyclooxygenase (COX-2), interleukin (IL)-1beta, and IL-12beta, was suppressed by
      DBO-M. Our data showed that DBO-M, which has relatively higher sugar content than
      DBOE and DBO-H, could play an important role in suppressing inflammatory
      responses by controlling pro-inflammatory cytokines and mediators. 

PMID- 27040633
TI  - Development, Characterization and Skin Interaction of Capsaicin-Loaded
      Microemulsion-Based Nonionic Surfactant.
AB  - The aim of this study was to develop novel microemulsions (MEs) for the
      transdermal delivery of capsaicin. Microemulsion-based nonionic surfactants
      consisting of isopropyl myristate as the oil phase, various nonionic surfactants
      as the surfactant (S), various glycols or alcohol as the co-surfactant (CoS), and
      reverse osmosis water as the aqueous phase were formulated. Based on the optimal
      ME obtained from Design Expert, MEs containing a fixed concentration of oil,
      water or surfactant were prepared while varying the amounts of the other two
      fractions. The results indicated that the skin permeation flux of low dose
      capsaicin (0.15% (w/w)) was significantly higher for the selected ME than the
      commercial product and capsaicin in ethanol (control) by approximately two- and
      four-fold, respectively. We successfully demonstrated the feasibility of the
      transdermal delivery of capsaicin-loaded ME using a low concentration of nonionic
      surfactant and ethanol. Moreover, the optimization using computer program helped
      to simplify the development of a pharmaceutical product.

PMID- 27040634
TI  - Evaluation of Antiemetic Therapy for Hepatic Transcatheter Arterial Infusion
      Chemotherapy with Cisplatin.
AB  - Antiemetic prophylaxis with aprepitant, a 5-hydroxytryptamine3 (5-HT3) receptor
      antagonist and dexamethasone is recommended for patients receiving intravenous
      cisplatin chemotherapy. Whether the same antiemetic regime is superior for
      hepatic transcatheter arterial infusion chemotherapy with cisplatin (CDDP-TAI) is
      unknown. We conducted a retrospective study of antiemetic prophylaxis protection
      against chemotherapy-induced nausea and vomiting (CINV) in CDDP-TAI at Nagasaki
      University Hospital. The rate of complete response (CR) to antiemetics in the
      acute (<24 h) and delayed phases (24-120 h) was measured. Twenty-four patients
      were treated with a 5-HT3 receptor antagonist (granisetron or azasetron) and
      dexamethasone on the day of chemotherapy (day 1 only). There was a significant
      difference between the CR rates in the acute and delayed phases, 91.6, and 69.7%,
      respectively. Combination of a 5-HT3 antagonist and dexamethasone on day 1 is
      effective against acute CINV, but not delayed CINV during CDDP-TAI. These results
      may help guide the management of nausea and vomiting during CDDP-TAI to achieve
      better tolerance and compliance for fewer interventions and increased favorable
      therapeutic outcomes. 

PMID- 27040635
TI  - Rapidity and Severity of Hemoglobin Decreasing Associated with Erythrocyte
      Inosine Triphosphatase Activity and ATP Concentration during Chronic Hepatitis C
      Treatment.
AB  - The purpose of this study was to evaluate the association between therapy-induced
      hemoglobin (Hb) decreasing rapidity and severity with erythrocyte inosine
      triphosphatase (ITPase) activity and ATP concentration in chronic hepatitis C
      patients receiving chronic hepatitis C (HCV) treatment. Forty-three Japanese
      patients were included in the study. Erythrocyte ITPase activity before therapy
      was determined by HPLC-UV. Erythrocyte ATP concentrations before and during
      therapy were determined by luciferase assay. Genotyping for ITPA 94C>A
      (rs1127354) and IVS2+21 A>C (rs7270101) was conducted using TaqMan probes. The
      median ITPase activity (umol/h/g hemoglobin) of ITPA 94 CC, CA, and AA genotypes
      was 136.8 (range, 80.4-289.6), 41.1 (24.3-93.1), and 11.8, respectively. ITPase
      activity and Hb decreasing showed a significantly inverse relationship at
      therapeutic weeks 2, 4, and 6 (p<0.01). Erythrocyte ATP concentration was
      decreased by therapy, and Hb decreasing was significantly and inversely
      correlated with erythrocyte ATP concentration at week 4 and after week 8 (p<0.001
      and 0.05, respectively). ATP concentration for patients with ITPA 94CA was
      significantly lower than ITPA 94CC at week 4 (p=0.045). We concluded that ITPase
      activity plays an important function and that ATP concentration changes due to
      therapy are related to the Hb decreasing mechanism in the early period of therapy
      with HCV treatment. 

PMID- 27040636
TI  - Analgesic Effects of 1st Generation Anti-histamines in Mice.
AB  - Pain is sensed, transmitted, and modified by a variety of mediators and
      receptors. Histamine is a well-known mediator of pain. In addition to their anti
      histaminic effects, the classical, or 1st generation, anti-histamines (1st AHs)
      possess, to various degrees, anti-muscarinic, anti-serotonergic, anti-adrenergic,
      and other pharmacologic effects. Although there have been attempts to use 1st AHs
      as analgesics and/or analgesic adjuvants, the advent of non-steroidal anti
      inflammatory drugs (NSAIDs) discouraged such trials. We previously reported that
      in patients with temporomandibular disorders, osteoporosis, and/or
      osteoarthritis, the analgesic effects of certain 1st AHs (chlorpheniramine and
      diphenhydramine) are superior to those of the NSAIDs flurbiprofen and
      indomethacin. Here, we compared analgesic effects among 1st AHs and NSAIDs
      against responses shown by mice to intraperitoneally injected 0.7% acetic acid.
      Since 1st AHs are water soluble, we selected water-soluble NSAIDs. For direct
      comparison, drugs were intravenously injected 30 min before the above tests.
      Histamine-H1-receptor-deficient (H1R-KO) mice were used for evaluating H1
      receptor-independent effects. The tested 1st AHs (especially cyproheptadine)
      displayed or tended to display analgesic effects comparable to those of NSAIDs in
      normal and H1R-KO mice. Our data suggest that the anti-serotonergic and/or anti
      adrenergic effects of 1st AHs make important contributions to their analgesic
      effects. Moreover, combination of a 1st AH with an NSAID (cyclooxygenase-1
      inhibitor) produced remarkably potent analgesic effects. We propose that a 1st
      AH, by itself or in combination with a cyclooxygenase-1 inhibitor, should undergo
      testing to evaluate its usefulness in analgesia. 

PMID- 27040637
TI  - The ETS Factor Myeloid Elf-1-Like Factor (MEF)/Elf4 Is Transcriptionally and
      Functionally Activated by Hypoxia.
AB  - Hypoxia-inducible factor (HIF)-1alpha is a transcription factor belonging to the
      HIF family that is activated in mammalian cells during conditions of low oxygen
      tension or hypoxia to induce an adaptive response and promote cell survival. Some
      of the genes targeted by HIF-1alpha are important for angiogenesis and
      proliferation. Here, we found that the E26 transformation-specific (ETS)
      transcription factor myeloid elf-1-like factor (MEF)/Elf4 is activated by HIF
      1alpha. MEF induces genes such as human beta-defensin 2 (HbetaD2) and perforin
      (PRF1), and is known to affect the cell cycle. Treatment with hypoxia mimetic
      CoCl2 or low O2 incubation up-regulated MEF mRNA and protein levels in various
      cell lines. HIF-1alpha overexpression in HEK293 cells also increased MEF mRNA and
      protein levels. In contrast, HIF-1alpha knockdown by small interfering RNA
      (siRNA) suppressed the induction of MEF in response to hypoxia. HIF-1alpha binds
      to the hypoxia response element in the MEF promoter region (-200 bp) and
      activates MEF promoter under hypoxia condition. The induction of MEF by
      hypoxia/HIF-1alpha correlated with the increase of MEF target genes HbetaD2 and
      PRF1. Intriguingly, the hypoxia-induced expression of HIF-1alpha target gene
      vascular endothelial growth factor (VEGF) was enhanced by the exogenous addition
      of MEF. Overall, these data indicate that hypoxia or HIF-1alpha positively
      regulates MEF expression and function. 

PMID- 27040638
TI  - Effect of Food Thickener on Dissolution and Laxative Activity of Magnesium Oxide
      Tablets in Mice.
AB  - The present study examined the dissolution of magnesium oxide (MgO) from MgO
      tablets placed in a food thickening agent (food thickener) and its effects on
      laxative activity. We prepared mixtures of MgO tablets suspended in an aqueous
      suspension and food thickeners in order to evaluate the dissolution of MgO. The
      results of the dissolution tests revealed that agar-based food thickeners did not
      affect the MgO dissolution. In contrast, some xanthan gum-based food-thickener
      products show dissolution rates with certain mixtures containing disintegrated
      MgO tablets suspended in a food thickener that decrease over time. However, other
      xanthan gum-based food-thickener products show dissolution rates that decrease
      immediately after mixing, regardless of the time they were allowed to stand. In
      order to investigate the laxative activity of MgO, we orally administered a
      mixture of MgO suspension and food thickener to mice and observed their bowel
      movements. The animal experiments showed that when agar-based food thickeners
      were used, the laxative activity of MgO was not affected, but it decreased when
      xanthan gum-based food thickeners were used. 

PMID- 27040639
TI  - Errata for Biological and Pharmaceutical Bulletin.

PMID- 27040640
TI  - Dcc Mediates Functional Assembly of Peripheral Auditory Circuits.
AB  - Proper structural organization of spiral ganglion (SG) innervation is crucial for
      normal hearing function. However, molecular mechanisms underlying the
      developmental formation of this precise organization remain not well understood.
      Here, we report in the developing mouse cochlea that deleted in colorectal cancer
      (Dcc) contributes to the proper organization of spiral ganglion neurons (SGNs)
      within the Rosenthal's canal and of SGN projections toward both the peripheral
      and central auditory targets. In Dcc mutant embryos, mispositioning of SGNs
      occurred along the peripheral auditory pathway with misrouted afferent fibers and
      reduced synaptic contacts with hair cells. The central auditory pathway
      simultaneously exhibited similar defective phenotypes as in the periphery with
      abnormal exit of SGNs from the Rosenthal's canal towards central nuclei.
      Furthermore, the axons of SGNs ascending into the cochlear nucleus had disrupted
      bifurcation patterns. Thus, Dcc is necessary for establishing the proper spatial
      organization of SGNs and their fibers in both peripheral and central auditory
      pathways, through controlling axon targeting and cell migration. Our results
      suggest that Dcc plays an important role in the developmental formation of
      peripheral and central auditory circuits, and its mutation may contribute to
      sensorineural hearing loss.

PMID- 27040641
TI  - Acute ischaemic lung injury due to pulmonary vascular obstruction.
AB  - AIMS: We have encountered cases of a distinctive myxomatous alveolar wall
      thickening around pulmonary infarctions, and have termed it 'acute ischaemic lung
      injury' (AILI). In this study we determined if pulmonary infarction is the only
      cause of AILI and have elucidated its histological features. METHODS AND RESULTS:
      We examined 2941 cases that underwent lobectomy, surgical lung biopsies for
      nodular lesions or autopsies between 1994 and 2014. Cases were divided into
      pulmonary infarction and non-infarction groups. The histological features of AILI
      sought were lobule-based alveolar wall thickening (myxomatous or fibrous) with
      epithelial metaplasia and negligible inflammation. In order to characterize AILI
      further, we performed immunohistochemical staining using several antibodies.
      Thirty-four of 69 cases in the infarction group (mean age 57.1 years, 30 males)
      had AILI, whereas only one (but with vascular obstruction) of the remaining 2872
      in the non-infraction group had AILI. AILI was located around infarctions.
      Separation of the epithelial and endothelial basement membranes of the alveolar
      wall was observed in 75% of cases. CONCLUSIONS: AILI is associated almost
      exclusively with lung infarction, caused presumably by vascular obstruction. We
      consider AILI to represent a distinct lung lesion other than pulmonary
      haemorrhage and infarction.

PMID- 27040642
TI  - Heterologous immunity meets tissue-specific training.

PMID- 27040643
TI  - Systems biology analysis of hepatitis C virus infection reveals the role of copy
      number increases in regions of chromosome 1q in hepatocellular carcinoma
      metabolism.
AB  - Hepatitis C virus (HCV) infection is a worldwide healthcare problem; however,
      traditional treatment methods have failed to cure all patients, and HCV has
      developed resistance to new drugs. Systems biology-based analyses could play an
      important role in the holistic analysis of the impact of HCV on hepatocellular
      metabolism. Here, we integrated HCV assembly reactions with a genome-scale
      hepatocyte metabolic model to identify metabolic targets for HCV assembly and
      metabolic alterations that occur between different HCV progression states
      (cirrhosis, dysplastic nodule, and early and advanced hepatocellular carcinoma
      (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential
      for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin
      sulfate was significantly changed in the cirrhosis stage, whereas the metabolism
      of acyl-carnitine was significantly changed in the dysplastic nodule and early
      HCC stages. Our results explained the role of the upregulated expression of
      BCAT1, PLOD3 and six other methyltransferase genes involved in carnitine
      biosynthesis and S-adenosylmethionine metabolism in the early and advanced HCC
      stages. Moreover, GNPAT and BCAP31 expression was upregulated in the early and
      advanced HCC stages and could lead to increased acyl-CoA consumption. By
      integrating our results with copy number variation analyses, we observed that
      GNPAT, PPOX and five of the methyltransferase genes (ASH1L, METTL13, SMYD2,
      TARBP1 and SMYD3), which are all located on chromosome 1q, had increased copy
      numbers in the cancer samples relative to the normal samples. Finally, we
      confirmed our predictions with the results of metabolomics studies and proposed
      that inhibiting the identified targets has the potential to provide an effective
      treatment strategy for HCV-associated liver disorders.

PMID- 27040644
TI  - Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the
      Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans.
AB  - Graphene oxide (GO) has been shown to cause multiple toxicities in various
      organisms. However, the underlying molecular mechanisms for GO-induced shortened
      longevity are still unclear. We employed Caenorhabditis elegans to investigate
      the possible involvement of insulin signaling pathway in the control of GO
      toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt
      1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while
      mutation of daf-16 gene led to a susceptible property of nematodes to GO
      toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1
      receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO
      transcription factor. Genetic interaction analysis suggested the involvement of
      signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on
      longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated
      that GO reduced longevity by affecting the functions of signaling cascade of DAF
      2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity
      on longevity by functioning upstream of SOD-3, which encodes an antioxidation
      system that prevents the accumulation of oxidative stress. Therefore, intestinal
      insulin signaling may encode two different molecular mechanisms responsible for
      the GO toxicity in inducing the shortened longevity. Our results highlight the
      key role of insulin signaling pathway in the control of GO toxicity in organisms.

PMID- 27040645
TI  - Obesity-initiated metabolic syndrome promotes urinary voiding dysfunction in a
      mouse model.
AB  - OBJECTIVE: Accumulating evidences suggests that obesity and metabolic syndrome
      (MetS) contribute towards lower urinary tract symptoms (LUTS) through alterations
      in the phenotype of bladder and prostate gland. Clinical studies indicate a link
      between MetS and LUTS. Nevertheless, there is lack of suitable animal model(s)
      which could illustrate an association linking obesity to LUTS. We examined the
      lower urinary tract function in an obesity-initiated MetS mouse model. METHODS:
      Male C57BL/6N wild-type and obese B6.V-Lepob/J maintained on regular diet for 28
      weeks were subjected to the assessment of body weight (BW), body length (BL),
      waist circumference (WC), body mass index (BMI), blood glucose (BG), plasma
      insulin (INS), plasma leptin (LEP), total cholesterol (CHO), free fatty acid
      (FFA), and measurement of urinary functions. Whole animal peritoneal and
      subcutaneous adipose tissue measurements as well as prostate and bladder volumes
      were analyzed by MRI followed by histological evaluation. These parameters were
      used to draw correlations between MetS and LUTS. RESULTS: Obesity parameters such
      as BW, WC, and BMI were significantly higher in B6.V-Lepob/J mice compared to
      C57BL/6N mice (P < 0.01). Higher levels of total CHO and FFA were noted in B6.V
      Lepob/J mice than C57BL/6N mice (P < 0.05). These results were concurrent with
      frequency, lower average urine volume and other urinary voiding dysfunctions in
      B6.V-Lepob/J mice. MRI assessments demonstrate marked increase in body fat and
      prostate volume in these mice. Compared to C57BL/6N mice, histological analysis
      of the prostate from B6.V-Lepob/J mice showed increased proliferation, gland
      crowding, and infiltration of immune cells in the stroma; whereas the bladder
      urothelium was slightly thicker and appears more proliferative in these mice. The
      regression and correlation analysis indicate that peritoneal fat (R = 0.853; P <
      0.02), CHO (R = 0.729; P < 0.001), BG (R = 0.712; P < 0.001) and prostate volume
      (R = 0.706; P < 0.023) strongly correlate with LUTS whereas BMI, WC, INS, and FFA
      moderately correlate with the prevalence of bladder dysfunction. CONCLUSION: Our
      results suggest that LUTS may be attributable in part to obesity and MetS.
      Validation of an in vivo model may lead to understand the underlying
      pathophysiological mechanisms of obesity-related LUTS in humans. Prostate 76:964
      976, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27040646
TI  - Effects of label-dose permethrin administration in yearling beef cattle: I.
      Reproductive function and embryo quality of superovulated heifers.
AB  - The objective was to study the effects of a commercial pyrethroid-based pour-on
      product, permethrin, on reproductive performance in superovulated beef heifers by
      assessing steroid biosynthesis and embryo quality. Nonpregnant, yearling beef
      heifers (n = 10; 418 +/- 33 kg; 5.5 +/- 0.2 body conditioning scores) were
      assigned by body weight and breed to either (1) saline control or (2) permethrin
      pour-on administered at label dose (PYR). Superovulation was achieved on all
      heifers using a timed, 17-day, CIDR-based protocol with GnRH and PGF2alpha and
      decreasing total dosage of 240-mg FSH administered twice daily for 4 days.
      Heifers were artificially inseminated twice (at onset of estrus and 12 hours
      later) by same technician with frozen semen from single bull collection. To
      determine short- and long-term effects of permethrin on embryo quality and
      steroid biosynthesis, superovulation was initiated twice with collection of
      embryos occurring at 17 and 51 days after treatment. Embryos were recovered 6.5
      days after first artificial insemination via nonsurgical flush and were evaluated
      by International Embryo Transfer Society standards. Blood was collected at
      standing estrus and day of embryo recovery. Estradiol (E2) and progesterone (P4)
      concentrations were analyzed via RIA. MIXED and GLIMMIX procedures of SAS were
      used to analyze continuous and categorical data, respectively. Heifer per flush
      was the experimental unit. Total embryos recovered did not differ because of
      treatment (P = 0.30), but did decrease in flush 2 compared with flush 1 (P =
      0.02). Quality grade, total transferable quality embryos, and overall flush
      success did not differ because of treatment (P >= 0.16). However, transferable
      quality embryos were decreased in flush 2 compared with flush 1 (P = 0.05). Total
      unfertilized oocytes were greater in saline control (P = 0.04). The PYR heifers
      tended to have less total P4 (P = 0.15) and P4 per CL (P = 0.06) at recovery. E2
      per ovulated follicle and E2 per total ovarian structure was greater in flush 2
      (P <= 0.03) but did not differ because of treatment (P >= 0.23). In summary,
      these data indicate that permethrin administration at label dose in superovulated
      beef heifers has a tendency to reduce P4, but embryo quality is not affected. 

PMID- 27040647
TI  - Feeding programs promoting daily feed intake stability in rabbit males reduce
      sperm abnormalities and improve fertility.
AB  - Feeding programs promoting daily feed intake (DFI) stability in rabbit males
      could be useful to ensure successful coverage of their nutritional requirements
      and for continued production of quality semen. To evaluate two feeding systems
      designed to reduce DFI variability, 115 rabbit males at age 1.2 years were
      randomly assigned to three different treatments for 294 days: CS, animals fed ad
      libitum with a control diet (127-g starch and 281-g total soluble fiber
      [hemicellulose + soluble fiber] kg(-1) dry matter); SF, males fed ad libitum with
      diet enriched in soluble fiber (86-g starch and 330-g total soluble fiber kg(-1)
      dry matter); and R, animals fed with CS diet but daily restricted to maintenance
      requirements. Feed intake, body weight, body condition, and variability of DFI
      were controlled every 42 days, and individual semen volume and sperm motility,
      concentration, acrosome status, and abnormalities every 15 days. In six
      commercial farms, the number of females inseminated, pregnant and kindling, as
      well as the number of kits born alive, was registered for 15,893 inseminations
      with pooled semen from each treatment. DFI was significantly lower for R males
      than for the other treatments (on average, -12 +/- 4 g/day; P < 0.001). Daily
      weight gain of R males was close to zero and significantly lower than in the
      other groups (-1.42 g/day; P < 0.001). Variability of DFI was significantly (P <
      0.01) lower for R males (7%) than for males of dietary treatments CS (13%), with
      SF males showing intermediate values (11%). Semen from R males presented lower
      sperm abnormalities (-5.9%; P < 0.05) and higher percentages of normal and motile
      spermatozoa (-3.4% than SF males; P < 0.05). Dietary treatments formulated to
      reduce DFI variability (SF and R) led to an improvement of kindling to pregnant
      and kindling to insemination ratio (+0.039 and + 0.060 +/- 0.015, respectively; P
      < 0.05) compared with CS treatment. In conclusion, a moderate restriction of
      rabbit males may be useful to fit their needs and provide a constant daily supply
      of nutrients, with some sperm morphologic characteristics being improved, as well
      as the fertility of their pooled semen. 

PMID- 27040648
TI  - Strength and ductility with {10?11} - {10?12} double twinning in a magnesium
      alloy.
AB  - Based on their high specific strength and stiffness, magnesium alloys are
      attractive for lightweight applications in aerospace and transportation, where
      weight saving is crucial for the reduction of carbon dioxide emissions.
      Unfortunately, the ductility of magnesium alloys is usually limited. It is
      thought that one reason for the lack of ductility is that the development of -
      double twins (DTW) cause premature failure of magnesium alloys. Here we show with
      a magnesium alloy containing 4 wt% lithium, that the same impressively large
      compression failure strains can be achieved with DTWs as without. The DTWs form
      stably across the microstructure and continuously throughout straining, forming
      three-dimensional intra-granular networks, a potential strengthening mechanism.
      We rationalize that relatively easier <c+a> slip characteristic of this alloy
      plastically relaxed the localized stress concentrations that DTWs can generate.
      This result may provide key insight and an alternative perspective towards
      designing formable and strong magnesium alloys. 

PMID- 27040649
TI  - Calotropis gigantea.

PMID- 27040650
TI  - Detection and Isolation of Digital Dermatitis Treponemes from Bovine Pressure
      Sores.
AB  - Pressure sores cause severe pain and discomfort in hospitalized people and in
      farmed cattle and are often infected with unknown bacteria. Pressure sores occur
      on the upper legs of 6-10% of recumbent cattle and are generally considered to be
      caused by constant pressure, commonly on bony areas of the limbs. This study
      analyzed pressure sores taken from the upper limbs of 14 cattle using isolation
      in culture and nested polymerase chain reaction (PCR) to detect treponemes
      associated with digital dermatitis (DD). A 100% association of DD treponemes with
      the pressure sores was demonstrated, but treponemes were shown not to be part of
      the normal skin microbiota. Immunohistochemistry showed an association of DD
      treponemes with lesions and particularly with the hair follicles in lesions,
      identifying the bacteria deep within wounds, thereby suggesting that they could
      contribute to lesion pathogenesis. The bacteria isolated from the pressure sore
      lesions were similar or identical on analysis of the 16S rRNA gene to those found
      in DD foot lesions in cattle, suggesting the same bacteria can infect multiple
      lesions. Indeed, the results of this study suggest that these spirochaetal
      bacteria may be expanding in host range and in their ability to colonize
      different tissues and contribute to a range of disease manifestations in farm
      animals. 

PMID- 27040651
TI  - Expression of cell cycle proteins in cortical neurons-Correlation with glutamate
      induced neurotoxicity.
AB  - Under physiological conditions, upon differentiation neurons become irreversibly
      post-mitotic by down-regulating cell cycle progression. However, recent studies
      have provided evidence that aberrant expression of cell cycle related proteins;
      especially cyclins, cyclin-dependent kinases, and their inhibitors are
      accompanied by programmed cell death in neurons. This abnormal phenotype has been
      postulated to contribute to the pathophysiology of different neurodegenerative
      diseases. Glutamate is the most abundant and major excitatory neurotransmitter in
      the central nervous system but high concentrations are reported to be involved in
      the pathology of many neurodegenerative diseases. The mechanisms of glutamate
      neurotoxicity have been intensively investigated over the past decades but still
      remain not fully understood. In this study, we hypothesized that aberrant
      regulation of cell cycle proteins may be involved in glutamate-induced
      neurotoxicity in primary cultures of rat cortical neurons. The results have shown
      that, glutamate treatment caused apoptosis by inducing active caspase-3 and p53
      expression. Together with this, an increase in cyclin D1 and Cdk4 protein levels,
      localization of cyclin D1 to nucleus, and a decrease in the cell cycle inhibitor
      p27 were observed. After glutamate treatment we also detected up-regulation of
      protein kinase C-alpha (PKC-alpha) protein expression. Altogether, the data
      reported in this study show for the first time that glutamate in cortical neurons
      changes simultaneously the expression levels of a number of key cell cycle
      proteins and cell homeostasis regulators. (c) 2016 BioFactors, 42(4):358-367,
      2016. 

PMID- 27040653
TI  - High-performance flexible hydrogen sensor made of WS2 nanosheet-Pd nanoparticle
      composite film.
AB  - We report a flexible hydrogen sensor, composed of WS2 nanosheet-Pd nanoparticle
      composite film, fabricated on a flexible polyimide substrate. The sensor offers
      the advantages of light-weight, mechanical durability, room temperature
      operation, and high sensitivity. The WS2-Pd composite film exhibits sensitivity
      (R 1/R 2, the ratio of the initial resistance to final resistance of the sensor)
      of 7.8 to 50,000 ppm hydrogen. Moreover, the WS2-Pd composite film distinctly
      outperforms the graphene-Pd composite, whose sensitivity is only 1.14.
      Furthermore, the ease of fabrication holds great potential for scalable and low
      cost manufacturing of hydrogen sensors.

PMID- 27040652
TI  - Effect of the achondroplasia mutation on FGFR3 dimerization and FGFR3 structural
      response to fgf1 and fgf2: A quantitative FRET study in osmotically derived
      plasma membrane vesicles.
AB  - The G380R mutation in the transmembrane domain of FGFR3 is a germline mutation
      responsible for most cases of Achondroplasia, a common form of human dwarfism.
      Here we use quantitative Foster Resonance Energy Transfer (FRET) and osmotically
      derived plasma membrane vesicles to study the effect of the achondroplasia
      mutation on the early stages of FGFR3 signaling in response to the ligands fgf1
      and fgf2. Using a methodology that allows us to capture structural changes on the
      cytoplasmic side of the membrane in response to ligand binding to the
      extracellular domain of FGFR3, we observe no measurable effects of the G380R
      mutation on FGFR3 ligand-bound dimer configurations. Instead, the most notable
      effect of the achondroplasia mutation is increased propensity for FGFR3
      dimerization in the absence of ligand. This work reveals new information about
      the molecular events that underlie the achondroplasia phenotype, and highlights
      differences in FGFR3 activation due to different single amino-acid pathogenic
      mutations. 

PMID- 27040654
TI  - Applying medicinal chemistry strategies to understand odorant discrimination.
AB  - Associating an odorant's chemical structure with its percept is a long-standing
      challenge. One hindrance may come from the adoption of the organic chemistry
      scheme of molecular description and classification. Chemists classify molecules
      according to characteristics that are useful in synthesis or isolation, but which
      may be of little importance to a biological sensory system. Accordingly, we look
      to medicinal chemistry, which emphasizes biological function over chemical form,
      in an attempt to discern which among the many molecular features are most
      important for odour discrimination. Here we use medicinal chemistry concepts to
      assemble a panel of molecules to test how heteroaromatic ring substitution of the
      benzene ring will change the odour percept of acetophenone. This work allows us
      to describe an extensive rule in odorant detection by mammalian olfactory
      receptors. Whereas organic chemistry would have predicted the ring size and
      composition to be key features, our work reveals that the topological polar
      surface area is the key feature for the discrimination of these odorants. 

PMID- 27040655
TI  - A Hematological Menace: Multiple Venous Thrombosis Complicated by Acquired Factor
      VIII Deficiency.
AB  - BACKGROUND: Acquired hemophilia A (AHA) classically presents with spontaneous
      bleeding of mucosal sites, GI tract, and subcutaneous tissues, often leading to
      large hematomas and ecchymosis. Among documented cases, 50% are idiopathic and
      few have been associated with trauma or surgery. We present a case of life
      threatening bleeding caused by AHA, following trauma and complicated by multiple
      venous thrombi. CASE REPORT: A 21-year-old man presented with multiple injuries
      secondary to trauma leading to extensive life-saving surgery. Two weeks post
      operatively, he developed multiple deep venous thrombi and was started on
      anticoagulation. Twenty-four days post-operatively, he started bleeding from
      multiple mucosal sites and developed an abdominal hematoma. Anticoagulation was
      stopped, with administration of fresh frozen plasma and vitamin K. Diagnosis of
      AHA was made based on low factor VIII level and presence of factor VIII
      inhibitors after an appropriate battery of tests ruled out other possible
      diagnoses. He was started on steroids and recombinant factor VIIa, leading to
      immediate improvement. Once stable, Rituximab infusions resulted in decreasing
      factor VIII inhibitor levels, with gradual normalization of PTT. CONCLUSIONS: AHA
      remains a diagnostic challenge because of its rarity, leading to delay in
      diagnosis and causing significant morbidity and mortality. Elevated PTT relative
      to PT/INR is a strong clue which should be followed by mixing studies. Very few
      cases have been associated with surgery or trauma and relatively few large,
      controlled trials have compared different treatment modalities for AHA. Growing
      evidence supports anti-CD20 (Rituximab) as an effective treatment option, as in
      this case.

PMID- 27040657
TI  - Delivery of tanshinone IIA and alpha-mangostin from gold/PEI/cyclodextrin
      nanoparticle platform designed for prostate cancer chemotherapy.
AB  - A new anti-cancer drug delivery system, based on gold nanoparticles, has been
      designed for hydrophobic active compounds. The system is a conjugate of
      gold/polyethyleneimine (AuNPs/PEI) nanoparticles and sulphated beta-cyclodextrin
      (CD). Anionic cyclodextrin was attached to the positively charged AuNPs/PEI
      nanoparticles by ionic bonds. Tanshinone IIA and alpha-mangostin were extracted,
      purified and encapsulated into the AuNPs/PEI/CD nanoparticles. In vitro
      preliminary cell viability assays against prostate cancer cell lines PC-3 and
      DU145 showed that encapsulation resulted in increased cytotoxicity.

PMID- 27040656
TI  - One-pot synthesis and antifungal activity against plant pathogens of
      quinazolinone derivatives containing an amide moiety.
AB  - An efficient one-pot, three-component synthesis of quinazolinone derivatives
      containing 3-acrylamino motif was carried out using CeO2 nanoparticles as
      catalyst. Thirty-nine synthesized compounds were obtained with satisfied yield
      and elucidated by spectroscopic analysis. Four phytopathogenic fungi were chosen
      to test the antifungal activities by minimum inhibitory concentration (MIC)
      method. Compounds 4ag, 4bb, 4bc showed broad antifungal activities against at
      least three fungi, and dramatic effects of substituents on the activities were
      observed. Docking studies were established to explore the potential antifungal
      mechanism of quinazolinone derivatives as the chitinase inhibitors, and also
      verified the importance of the amide moiety. 

PMID- 27040658
TI  - Design, synthesis and cytotoxicity of pyrano[4,3-b]indol-1(5H)-ones: A hybrid
      pharmacophore approach via gold catalyzed cyclization.
AB  - Reported herein is the gold(III)-catalyzed 6-endo-dig cycloisomerization of 2
      alkynyl-indole-3-carboxylic acids to form pyrano[4,3-b]indol-1(5H)-ones, which
      are pharmaceutically important structural motifs. The hitherto unknown substrates
      required for this methodology were conveniently synthesized in five steps with
      good overall yields. The utility of this new cycloisomerization is demonstrated
      by the excellent regioselectivity obtained using a range of substrates. The
      mildness of the method allowed functional group compatibility towards hydroxyl
      tether, displaying exquisite chemoselectivity. All the synthesized compounds were
      screened for their tumor cell growth inhibitory activity against human cervix
      adenocarcinoma (HeLa). Compound 7d emerged as the most active (IC50=0.69MUM)
      among the tested series compared to the standard cis-platin (IC50=0.08MUM).

PMID- 27040660
TI  - Antibacterial activity of Mannich bases derived from 2-naphthols, aromatic
      aldehydes and secondary aliphatic amines.
AB  - A small library of 1-aminoalkyl 2-naphthols has been synthesized through the
      direct Mannich reaction of 2-naphthols with (hetero)aromatic aldehydes and
      secondary amines. All of the Mannich bases having a thiophen-2-yl ring in their
      structure had good activity against Gram-positive bacteria, irrespective of the
      nature of the amino moiety.

PMID- 27040659
TI  - Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition
      on prostaglandin E2 production in LPS-induced murine and human macrophages cell
      lines.
AB  - The syntheses and bioactivities of symmetrical curcumin and its analogues have
      been the subject of interest by many medicinal chemists and pharmacologists over
      the years. To improve our understanding, we have synthesized a series of
      unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on
      prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937
      cells. Initially, compounds 8b and 8c exhibited strong inhibition on the
      production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01MUM and 8c,
      IC50=4.86MUM) and U937 (8b, IC50=3.44MUM and 8c, IC50=1.65MUM) cells. Placing
      vanillin at position Ar2 further improved the potency when both compounds 15a and
      15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78MUM
      and 15b, IC50=1.9MUM while U937: 15a, IC50=0.95MUM and 15b, IC50=0.92MUM).
      Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the
      activity of downstream inflammatory COX-2 mediator. Finally, docking simulation
      on protein targets COX-2, IKK-beta, ERK, JNK2, p38alpha and p38beta were
      performed using the conformation of 15a determined by single-crystal XRD.

PMID- 27040661
TI  - Synthesis, biological evaluation and molecular docking studies of 2-amino-3,4,5
      trimethoxyaroylindole derivatives as novel anticancer agents.
AB  - A series of novel 2-amino-3,4,5 trimethoxyaroylindole derivatives was synthesized
      and evaluated against selected human cancer cell lines of breast (MCF-7) and
      colon (HT-29). Introduction of an amino group at the C-2 position on ring A of
      3,4,5-trimethoxyaroylindole derivatives resulted in novel compounds, i.e., 2
      amino-3,4,5-trimethoxyaroylindole derivatives exhibiting excellent cytotoxic
      activity against human cancer cell lines. Substitution with methoxy group at R(6)
      in 2-amino-3,4,5-trimethoxyaroylindole 5d exhibited excellent cytotoxic activity
      against MCF-7 (0.013 MUM) and colon HT-29 (0.143 MUM) indicating slightly higher
      potency than Combretastatin A-4. Molecular modeling studies of 2-amino-3,4,5
      trimethoxyaroylindole derivatives have similar structural alignment as colchicine
      in protein (PDB code: 1SA0) and exhibited hydrogen bond interaction between para
      position of 3,4,5-trimethoxyphenyl ring with CYS 241 and N-H molecule of indole
      ring with Val 315 of receptor molecule.

PMID- 27040662
TI  - Efficient synthesis of new 2,3-dihydrooxazole-spirooxindoles hybrids as
      antimicrobial agents.
AB  - Two series of new 2,3-dihydrooxazole-spirooxindole derivatives were efficiently
      synthesized starting from N'-(2-oxoindolin-3-ylidene) benzohydrazide/N'-(2
      oxoindolin-3-ylidene)-2-phenoxyacetohydrazide using designed synthetic route.
      Newly synthesized 2,3-dihydrooxazole-spirooxindole derivatives were screened for
      their antibacterial and antifungal activity against different pathogenic strain
      of bacteria and fungi. The minimum inhibitory concentration (MIC), minimum
      bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) were
      determined for the test compounds as well as for reference standards. Compounds
      4e, 4g, 7g have shown good antibacterial activity whereas compounds 4f, 7b, 7d
      have displayed better antifungal activity.

PMID- 27040663
TI  - [Complicated diverticular disease debuting as necrotising fasciitis of pelvic
      limb. A case report].
AB  - BACKGROUND: Diverticular disease, and the diverticulitis, the main complication
      of it, are widely studied diseases with multiple chronic cases reported in the
      literature, but there are no atypical presentations with extra-abdominal symptoms
      coupled with seemingly unrelated entities, such as necrotising fasciitis.
      CLINICAL CASE: Female 52 years old, was admitted to the emergency department with
      back pain of 22 days duration. History of importance: Chronic use of
      benzodiazepines intramuscularly. Physical examination revealed the presence of a
      gluteal abscess in right pelvic limb with discoloration, as well as peri-lesional
      cellulitis and crepitus that stretches across the back of the limb. Fasciotomy
      was performed with debridement of necrotic tissue. Progression was torpid with
      crackling in abdomen. Computed tomography showed free air in the cavity, and on
      being surgically explored was found to be complicated diverticular disease.
      DISCUSSION: It is unusual for complicated diverticular disease to present with
      symptoms extra-peritoneal (< 2%) and even more so that a diverticulitis is due to
      necrotising fasciitis (< 1%). The absence of peritoneal manifestations delayed
      the timely diagnosis, which was evident with the crackling of the abdomen and
      abdominal computed tomography scan showing the parietal gaseous process.
      CONCLUSION: All necrotising fasciitis needs an abdominal computed tomography scan
      to look for abdominal diseases (in this case diverticulitis), as their
      overlapping presentation delays the diagnosis and consequently the treatment,
      making a fatal outcome inevitable.

PMID- 27040664
TI  - Corrigendum to "ApoER2 and reelin are expressed in regenerating peripheral nerve
      and regulate Schwann cell migration by activating the Rac1 GEF protein,
      Tiam1"[Mol Cell Neurosci 69C (2015) 1-11].

PMID- 27040665
TI  - Influence of Mild Traumatic Brain Injury (TBI) and Posttraumatic Stress Disorder
      (PTSD) on Pain Intensity Levels in OEF/OIF/OND Veterans.
AB  - OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder
      (PTSD) are common among US veterans of Operation Enduring Freedom/Operation Iraqi
      Freedom/Operation New Dawn (OEF/OIF/OND). We postulated that these injuries may
      modulate pain processing in these individuals and affect their subjective pain
      levels. DESIGN: Cross-sectional. SUBJECTS: 310 deployed service members of
      OEF/OIF/OND without a lifetime history of moderate or severe TBI were included in
      this study. METHODS: All participants completed a comprehensive evaluation for
      Blast Exposure, mTBI, PTSD, and Pain Levels. The Boston Assessment of TBI
      Lifetime Version (BAT-L) was used to assess blast exposure and potential brain
      injury during military service. The Clinician-Administered PTSD Scale (CAPS)
      characterized presence and severity of PTSD. The Visual Analog Scale (VAS) was
      used to assess pain intensity over the previous month before the interview, with
      higher scores indicative of worse pain. Statistical analysis was performed by
      ANOVA and results were adjusted for co-morbidities, clinical characteristics and
      demographic data. RESULTS: In comparison to control participants (veterans
      without mTBI or current PTSD), veterans with both current PTSD and mTBI reported
      the highest pain intensity levels, followed by veterans with PTSD only (P <
      0.0001 and P = 0.0005, respectively). Pain levels in veterans with mTBI only were
      comparable to control participants. CONCLUSIONS: Comorbid PTSD and mTBI is
      associated with increased self-reported pain intensity. mTBI alone was not
      associated with increased pain.

PMID- 27040666
TI  - Listening to Their Words: A Qualitative Analysis of Integrative Medicine Group
      Visits in an Urban Underserved Medical Setting.
AB  - OBJECTIVE: Integrative Medicine Group Visits (IMGVs) are an 8-week outpatient
      medical group visit program for chronic pain patients combining mindfulness-based
      stress reduction (MBSR), integrative medicine, and patient education. The authors
      conducted a qualitative study with IMGV participants to better understand the
      effects of IMGVs on patients' health. DESIGN: This qualitative study enrolled a
      convenience sample of 19 participants from the parent prospective observational
      cohort study of IMGVs (n = 65). All participants in the parent study were invited
      to participate. SETTING: Boston Medical Center (BMC) is a private, not-for
      profit, 496-bed, academic medical center and the largest safety net hospital in
      New England. SUBJECTS: Individuals in this study had a diagnosis of chronic pain
      and/or one or more chronic conditions (e.g., diabetes, depression, or metabolic
      syndrome), had attended >=1 group visit, and their 8-week session had ended
      before completing the interview. METHODS: The authors conducted individual semi
      structured interviews. Interviews were audio-taped, transcribed, and analyzed.
      RESULTS: Participants cite gains from IMGVs including improved self-monitoring,
      self-regulation, and increased mindfulness. The group setting leads patients to
      feel "not alone" in their health conditions, gain a sense of perspective on their
      health, and share coping strategies in a supportive network. These improvements
      in physical and mental health improved clinical outcomes for participants
      including reductions in pain. CONCLUSIONS: Group visits and integrative medicine
      both offer some potential solutions in the treatment of chronic pain. Models such
      as IMGVs can help individuals living with chronic conditions, addressing their
      emotional and physical health needs.

PMID- 27040667
TI  - Improving Access to Chronic Pain Services Through eConsultation: A Cross
      Sectional Study of the Champlain BASE eConsult Service.
AB  - OBJECTIVE: To describe the impact of the Champlain BASE (Building Access to
      Specialists through eConsultation) eConsult service on access to specialist care
      for patients with chronic pain. DESIGN: A cross-sectional descriptive study
      SETTING: The Champlain Local Health Integration Network, comprising Ottawa,
      Canada, and the surrounding region. SUBJECTS: All eConsult cases submitted to
      chronic pain specialists by primary care providers between April 15, 2011 and
      June 30, 2015. METHODS: Usage data and provider responses to a mandatory closeout
      survey were analyzed to determine response times, case outcomes, and provider
      satisfaction. RESULTS: Ninety-three primary care providers submitted 199
      eConsults to four chronic pain specialists during the study period. Submitted
      cases had median response times of 1.9 days. Thirty-six percent of cases resulted
      in an unnecessary referral being avoided, and over 90% of cases were rated by
      primary care providers as being of high or very high value for their patients and
      themselves. CONCLUSION: The eConsult service improved access to specialist care
      for patients with chronic diseases. By facilitating prompt communication between
      primary care providers and specialists, eConsult can help mitigate the negative
      effects of long wait times experienced by patients with chronic pain.

PMID- 27040668
TI  - Gabapentin Superadded to a Pre-Existent Regime Containing Amytriptyline for
      Chronic Sciatica.
AB  - SETTING: There is currently a gross lack of evidence base guiding the medical
      management of chronic sciatica (CS). Only scant previous studies have assessed
      gabapentin (GBP) in CS. Extrapolating NICE-UK guidelines, prescribing authorities
      often insist on trialling anti-depressants (e.g., amytriptyline, AMP) as a first
      line for neuropathic pain states such as CS. When super-adding second-line
      agents, such as GBP, NICE-UK encourages overlap with first-line agents to avoid
      decreased pain-control. No study has reflected this practice. OBJECTIVE: Evaluate
      efficacy and side effects (SE) of GBP superadded to a pre-existent regime
      containing AMP for CS. SUBJECTS AND METHODS: Prospective cohort of patients with
      unilateral CS attending a specialist spine clinic. Eligible patients had
      experienced partial benefit to a pre-existent regime containing AMP: none had
      significant SE. No drugs other than GBP were added or discontinued (the latter
      was considered inequitable) for 3 months. Visual analog pain score (VAS),
      Oswestry disability index (ODI), and SE were recorded. RESULTS: Efficacy: in 56%
      (43/77) there were reductions in VAS (5.3 +/- 3.6->2.8 +/- 2.7, P < 0.0001) and
      ODI (42.8 +/- 31.1->30.7 +/- 25.2, P = 0.008). SE: Eighty-two SE (23 types) were
      reported in 53% (41/77). Efficacy was less in those with SE: a trend existed for
      a lesser reduction in VAS (2.0 +/- 2.4 v 3.0 +/- 2.7, P = 0.08), which proved
      significant for ODI (8.1 +/- 11.4 v 16.7 +/- 18.2, P = 0.01). Thirty-four percent
      (26/77) discontinued GBP all within 1 week (i.e., during titration). CONCLUSION:
      This is the first prospective cohort study of GBP super-added to a pre-existent
      regime containing AMP for CS, as per routine clinical practice and NICE-UK
      principles. Super-added GBP demonstrated further efficacy over the previous
      regime in 56%; however, SE were frequent (53%) and diverse (23 types), and 34%
      abruptly discarded GBP. Although SE were associated with decreased efficacy, 37%
      nevertheless tolerated GBP despite SE.

PMID- 27040669
TI  - Effects of dipeptidyl peptidase-4 (DPP-4) inhibition on angiogenesis and hypoxic
      injury in type 2 diabetes.
AB  - AIMS: We examined whether, in diabetic Ob/Ob mice, the dipeptidyl peptidase-4
      (DPP-4) inhibitor (PKF275-055), an antihyperglycemic drug, that inhibits the
      biological inactivation of SDF-1 (stromal cell-derived factor-1), may increase
      endothelial progenitor cells (EPCs) mobilization and incorporation, which, in
      turn, may regenerate capillaries and reduce myocardial ischemia induced by
      strenuous exercise. MAIN METHODS: Half of sixteen control and Ob/Ob mice and
      eight Ob/Ob mice treated with PKF275-055 for four weeks underwent a forced swim
      protocol. Oral glucose tolerance, circulating EPCs, capillary ultrastructure and
      density, hypoxic areas and SDF-1 localization in myocardium were measured. KEY
      FINDINGS: Ob/Ob mice were glucose intolerant, had a significant low number of
      circulating EPCs and myocardial capillaries compared to lean controls. The DPP-4
      inhibitor significantly improved their glucose tolerance, doubled the number of
      circulating EPCs, stimulated the formation of functional vessels and SDF-1
      localization in the endothelium of myocardial capillaries and arterioles. Cardiac
      hypoxia after forced swim in Ob/Ob mice was significantly reduced when they were
      treated with the DPP-4 inhibitor. SIGNIFICANCE: DPP-4 inhibition may re-establish
      an adequate capillary network in the myocardium of diabetic Ob/Ob mice by the
      mobilization and SDF-1-mediated incorporation of EPCs and, consequently, reducing
      the susceptibility to myocardial ischemic injury provoked by strenuous exercise.

PMID- 27040670
TI  - Modulation of inflammatory and oxidative status by exercise attenuates cardiac
      morphofunctional remodeling in experimental Chagas cardiomyopathy.
AB  - AIMS: The rational basis that explains the benefits of exercise therapy on Chagas
      cardiomyopathy (ChC) is poorly understood. This study investigated the impact of
      an exercise program on exercise performance, heart parasitism, immunoinflammatory
      response, fibrogenesis, oxidative damage, and cardiomyocytes contractility in
      experimental ChC. MAIN METHODS: Wistar rats were subjected to a 9-week treadmill
      running training and challenged with Trypanosoma cruzi. Control animals remained
      sedentary. Physical and metabolic performance, cardiac morphology, cytokines,
      chemokines, nitric oxide, oxidative tissue damage, cardiomyocyte morphology and
      contractility were analyzed. KEY FINDINGS: Exercise training was efficient to
      improve physical performance and anaerobic threshold in trained animals. By
      increasing cardiac and serum levels of cytokines (TNF-alpha, IFN-gamma, and IL
      6), chemokines (MCP-1 and CX3CL1), the myocardial activity catalase and
      superoxide dismutase, and reducing lipid and protein oxidation in cardiac tissue,
      exercise training seem to be a beneficial strategy to mitigate the progression
      and severity of Chagas-associated cardiomyopathy. SIGNIFICANCE: The protective
      adaptations to the host triggered by exercise training contributed to reduce
      cardiac parasitism, inflammation, fibrosis and cardiomyocytes atrophy. Although
      exercise training does not affect nitric oxide levels in cardiac tissue from
      infected animals, this strategy enhanced the efficiency of endogenous antioxidant
      mechanisms, restricting oxidative tissue damage with positive repercussions to
      cardiomyocytes biomechanics in rats.

PMID- 27040672
TI  - Editorial Commentary: The success of heart rate control in the treatment of
      chronic heart failure.

PMID- 27040671
TI  - Dual control system - A novel scaffolding architecture of an inducible regulatory
      device for the precise regulation of gene expression.
AB  - Here, we present a novel scaffolding architecture of an inducible regulatory
      device. This dual control system is completely silent in the off stage and is
      coupled to the regulation of gene expression at both the transcriptional and
      translational levels. This system also functions as an AND gate. We demonstrated
      the effectiveness of the cumate-riboswitch dual control system for the control of
      pamamycin production in Streptomyces albus. Placing the cre recombinase gene
      under the control of this system permitted the construction of synthetic devices
      with non-volatile memory that sense the signal and respond by altering DNA at the
      chromosomal level, thereby producing changes that are heritable. In addition, we
      present a library of synthetic inducible promoters based on the previously
      described cumate switch. With only one inducer and different promoters, we
      demonstrate that simultaneous modulation of the expression of several genes to
      different levels in various operons is possible. Because all modules of the AND
      gates are functional in bacteria other than Streptomyces, we anticipate that
      these regulatory devices can be used to control gene expression in other
      Actinobacteria. The features described in this study make these systems promising
      tools for metabolic engineering and biotechnology in Actinobacteria.

PMID- 27040673
TI  - Tubercular osteomyelitis of the first metatarsal bone as a cause of forefoot
      pain.
AB  - The reporting of isolated metatarsal tuberculosis in the available literature is
      sparse, herein we report a case of 26-year-old female who presented with
      insidious onset pain and swelling in her forefoot. Radiograph showed osteolysis
      of the first metatarsal. Magnetic resonance imaging showed osseous erosion with
      marrow oedema. Diagnosis was ascertained by fine needle aspiration cytology of
      the lesion. The patient received anti-tubercular therapy and showed good clinical
      outcome. This case is reported because of its rarity of involving isolated
      metatarsal bone as a cause of forefoot pain. 

PMID- 27040674
TI  - Cadmium Concentration in Mother's Blood, Milk, and Newborn's Blood and Its
      Correlation with Fatty Acids, Anthropometric Characteristics, and Mother's
      Smoking Status.
AB  - The aim of this study was to determine cadmium concentration in mothers' blood,
      milk, and newborns' blood from Szczecin (Poland) as a result of environmental
      cadmium exposure and evaluate the correlation (1) between cadmium levels in
      analyzed matrices, (2) between cadmium and fatty acids in those matrices, and (3)
      between cadmium and some selected personal variables, such as anthropometric
      characteristics, mothers' smoking status, and fruit and fish consumption by
      mothers. The concentration of cadmium in whole blood and milk of mothers and in
      the umbilical cord blood of newborns was determined by atomic absorption
      spectrometry with graphite furnace atomization and Zeeman correction. The fatty
      acid concentrations were determined by gas chromatography in our previous study.
      The mean concentrations of cadmium in maternal blood, newborn's blood, and breast
      milk were 0.61 +/- 0.62 MUg/L, 0.05 +/- 0.04 MUg/L, and 0.11 +/- 0.07 MUg/L,
      respectively, and differed significantly between analyzed matrices. Cadmium
      concentrations in the umbilical cord blood were 15 % (range 0-83 %) of the
      concentration in maternal blood, whereas cadmium concentrations in breast milk
      constituted 35 % (range 3-142 %) of the concentration in mothers' blood. No
      correlation was found between cadmium levels in three analyzed matrices. The
      correlation analysis revealed significant low positive correlation between
      maternal blood cadmium concentrations and concentrations of elaidic, oleic, and
      cis-vaccenic acids in mothers' milk (correlation coefficients 0.30, 0.32, and
      0.31, respectively). Mothers' blood cadmium correlated with mothers' age (r = 
      0.26, p = 0.03), maternal smoking before pregnancy (r = 0.55, p < 0.000),
      maternal smoking during pregnancy (r = 0.58, p < 0.000), and fruit consumption by
      mothers after delivery (r = -0.44, p = 0.003). Mothers' height was the only
      variable that correlated significantly with breast milk cadmium levels. Newborns'
      blood cadmium concentrations correlated significantly with mothers' height (r =
      0.28, p = 0.02), newborns' birth weight (r = 0.26, p = 0.03), maternal smoking
      during pregnancy (r = 0.24, p = 0.048), and fish consumption by mothers after
      delivery (r = 0.37, p = 0.02). The concentrations of cadmium in Polish mother
      newborn pairs are among the lowest in Europe and within the norms established by
      different institutions. The results of our study confirm the existence of
      effective partial barriers (such as the placenta and mammary gland) restricting
      cadmium passage from mother to newborn. The significant positive correlations
      between maternal blood Cd and concentrations of oleic, elaidic, and cis-vaccenic
      acids in breast milk might suggest the increased cadmium toxicity to infant,
      taking into consideration even low cadmium passage to milk. Maternal smoking
      during pregnancy increases both maternal and newborn's blood cadmium level.
      Promotion of nonsmoking among pregnant women could substantially reduce prenatal
      and neonatal exposure to cadmium. Moreover, the results of our study point to the
      need of establishing complex biomonitoring of cadmium in mother-infant pairs in
      order to better protect children from this toxic and carcinogenic metal exposure.

PMID- 27040675
TI  - A new mutation in an infant with Krabbe disease accompanied by enlargement of the
      optic nerves.

PMID- 27040676
TI  - Effect of miR-26a-5p on the Wnt/Ca(2+) Pathway and Osteogenic Differentiation of
      Mouse Adipose-Derived Mesenchymal Stem Cells.
AB  - Elucidation of the molecular mechanisms that regulate the differentiation of
      adipose-derived mesenchymal stem cells into osteogenic cells may lead to new
      methods for bone tissue engineering. We examined the role of miR-26a-5p in the
      regulation of osteogenic differentiation of mouse adipose-derived mesenchymal
      stem cells (mADSCs) by using mimics and inhibitors of this microRNA. Our results
      showed that over-expression of miR-26a-5p inhibited osteogenesis and that
      suppression of endogenous miR-26a-5p promoted osteogenesis. Four bioinformatics
      algorithms indicated that the 3'UTR of Wnt5a was a potential target of miR-26a
      5p. We confirmed this prediction by use of dual-luciferase reporter assay and
      GFP/RFP assay. We also examined the molecular mechanisms by which miR-26a-5p
      regulates osteogenesis. Fura-2AM and Western blot assays after transfection
      indicated that miR-26a-5p repressed WNT5A, inhibited calcium flux and protein
      kinase C, and suppressed osteogenic differentiation of mADSCs. By contrast, miR
      26a-5p inhibition activated these signal proteins and promoted osteogenic
      differentiation. Taken together, our results suggest that up-regulation of miR
      26a-5p inhibits osteogenic differentiation of mADSCs by directly targeting the
      3'UTR of Wnt5a, thereby down-regulating the Wnt/Ca(2+) signaling pathway.

PMID- 27040677
TI  - NVVC/NHJ Durrer prizes 2015.
AB  - At the annual 2016 Spring Congress of the NVVC, the Durrer prizes were awarded to
      the authors of two of the best original articles published in the year 2015, one
      paper being more basically oriented and one paper being more clinically oriented.
      This annual tradition has existed since the year 2006. 

PMID- 27040678
TI  - Regular pulse rate but irregular heart rate?

PMID- 27040679
TI  - Regular pulse rate but irregular heart rate?

PMID- 27040680
TI  - Simvastatin effects on detoxification mechanisms in Danio rerio embryos.
AB  - The transcription and protein activity of defence mechanisms such as ABC
      transporters, phase I and II of cellular detoxification and antioxidant enzymes
      can be altered in the presence of emerging contaminants such as pharmaceuticals
      impacting the overall detoxification mechanism. The present work aimed to
      characterise the effects of simvastatin on the detoxification mechanisms of
      embryonic stages of Danio rerio. In a first approach, constitutive transcription
      of key genes involved in detoxification was determined. Embryos were collected at
      different developmental stages, and transcription patterns of genes coding for
      ABC transporters, phase I and II and oxidative stress were analysed. With
      exception of abcc2, all genes seem to be from maternal transfer (0-2 hpf).
      Embryos were then exposed to different concentrations of simvastatin (5 and 50
      MUg/L), verapamil and MK571 (10 MUM; ABC protein inhibitors) and a combination of
      simvastatin and ABC inhibitors. mRNA expression levels of abcb4, abcc1, abcc2,
      abcg2, cyp1a, cyp3a65, gst, sod, cat was evaluated. Accumulation assays to
      measure ABC proteins activity and activity of EROD, GST, CAT and Cu/ZnSOD, were
      also undertaken. Simvastatin acted as a weak inhibitor of ABC proteins and
      increased EROD and GST activity, whereas Cu/ZnSOD and CAT activity were
      decreased. Simvastatin up-regulated abcb4 and cyp3a65 transcription (both
      concentrations), as well as abcc1 and abcc2 at 50 MUg/L, and down-regulated gst,
      sod, cat at 5 MUg/L. In conclusion, our data revealed the interaction of
      simvastatin with detoxification mechanisms highlighting the importance of
      monitoring the presence of this emerging contaminant in aquatic environments. 

PMID- 27040681
TI  - Assessment of indoor climate of Mogila Abbey in Krakow (Poland) and the
      application of the analogues method to predict microclimate indoor conditions.
AB  - The microclimatic monitoring of the historic church of Mogila Abbey (Krakow,
      Poland) was carried out to study the impact of the environmental parameters on
      the organic and hygroscopic artworks. Specific indexes were proposed to
      objectively assess the quality of time series of temperature (T), relative
      humidity (RH), and carbon dioxide (CO2) before applying the exploratory data
      analysis. The series were used to define the historic environmental conditions as
      stated in the European Standard EN 15757:2010 and with the use of the climate
      evaluation chart (CEC). It was found that the percentage of time in which T and
      RH values are within the allowable limits of the ASHRAE (2011) Class B is more
      than 85 %. This means that, for about 15 % of the time, there is a high risk of
      mechanical damage to highly vulnerable objects mainly due to the RH variability.
      The environment at the chancel resulted moister than that at the cornice, and the
      fungal growth is possible. In addition, the time-weighted preservation index
      (TWPI) is computed to evaluate the life expectancy of the objects, taking into
      account the environmental conditions of the site under study. The method of
      analogues, developed to predict the evolution of a system given observations of
      the past and without the knowledge of any equation among variables, was proposed
      and applied to the time series of temperature, relative humidity, and carbon
      dioxide with a 1-h sampling time to avoid the influence of the autocorrelation.

PMID- 27040682
TI  - The ethylene response factor OsERF109 negatively affects ethylene biosynthesis
      and drought tolerance in rice.
AB  - Drought is an important factor limiting plant development and crop production.
      Dissecting the factors involved in this process is the key for enhancement of
      plant tolerance to drought stress by genetic approach. Here, we evaluated the
      regulatory function of a novel rice ethylene response factor (ERF) OsERF109 in
      drought stress. Expression of OsERF109 was rapidly induced by stress and
      phytohormones. Subcellular localization and transactivation assay demonstrated
      that OsERF109 was localized in nucleus and possessed transactivation activity.
      Transgenic plants overexpressing (OE) and knockdown with RNA interfering (RI)
      OsERF109 exhibited significantly reduced and improved drought resistance,
      respectively, indicating that OsERF109 negatively regulates drought resistance in
      rice. Furthermore, measurement by gas chromatography showed that ethylene
      contents were less in OE while more in RI lines than these in wild types,
      supporting the data of drought tolerance and water loss in transgenic lines.
      Quantitative real-time PCR analysis also proved the regulation of OsERF109 in the
      expression of OSACS6, OSACO2, and OsERF3, which have been identified to play
      important roles in ethylene biosynthesis. Based on these results, our data
      evidence that OsERF109 regulates drought resistance by affecting the ethylene
      biosynthesis in rice. Overall, our study reveals the negative role of OsERF109 in
      ethylene biosynthesis and drought tolerance in rice.

PMID- 27040683
TI  - Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell
      dyscrasias.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that may
      cause life-threatening hemorrhages in patients with plasma cell dyscrasias
      (PCDs). Early diagnosis and treatment require a thorough understanding of its
      underlying pathophysiology. Two patients with IgG MGUS presented with
      dramatically decreased plasma von Willebrand factor (VWF) and a severe type-1
      pattern on multimer analysis. A prompt response to intravenous immunoglobulins
      (IVIG), but not to VWF/FVIII, was consistent with accelerated immunologic
      clearance of plasma VWF. Another IgG MGUS patient showed a type-2 pattern and a
      less pronounced response to IVIG, suggesting that additional mechanism(s)
      contributed to AVWS evolution. In a patient with Waldenstrom's macroglobulinemia
      and severe depletion of plasma VWF, multimer analysis indicated association of
      the IgM paraprotein with VWF before, but not after plasmapheresis, resulting in
      destruction of the agarose gel and a characteristically distorted band structure
      of VWF multimers. A type-2 pattern with highly abnormal VWF triplets and
      laboratory evidence of excessive fibrinolytic activity suggested that plasmin
      mediated VWF degradation contributed to AVWS in a patient with multiple myeloma
      (MM) and AL amyloidosis. Finally, in a patient with IgG MM, maximally prolonged
      PFA-100(r) closure times and a specific defect in ristocetin-induced platelet
      agglutination, both of which resolved after remission induction, indicated
      interference of the paraprotein with VWF binding to platelet GPIb. Importantly,
      in none of the six patients, circulating autoantibodies to VWF were detected by a
      specific in-house ELISA. In summary, when evaluating PCD patients with severe
      bleeding symptoms, AVWS due to various pathogenic mechanisms should be
      considered. 

PMID- 27040684
TI  - In vivo imaging of cortical interneurons migrating in the
      intermediate/subventricular zones.
AB  - We developed an imaging system that enables migrating cortical interneurons (CIs)
      through the lower intermediate zone/subventricular zone (IZ/SVZ) in mouse
      embryos. CIs were labeled by in utero electroporation performed at embryonic day
      (E) 11.5 and were observed, through the skull of living embryos, detached from
      the dam with the umbilical cord remain attached. To identify imaged cell
      locations, we used GAD67-GFP mice and GFP fluorescence was photo-bleached after
      the recording. We found that CIs in the IZ/SVZ migrated medially straight toward
      the midline on the tangential plane, while those in the marginal zone migrated in
      all directions. 

PMID- 27040685
TI  - Person-Specific Non-shared Environmental Influences in Intra-individual
      Variability: A Preliminary Case of Daily School Feelings in Monozygotic Twins.
AB  - Most behavioural genetic studies focus on genetic and environmental influences on
      inter-individual phenotypic differences at the population level. The growing
      collection of intensive longitudinal data in social and behavioural science
      offers a unique opportunity to examine genetic and environmental influences on
      intra-individual phenotypic variability at the individual level. The current
      study introduces a novel idiographic approach and one novel method to investigate
      genetic and environmental influences on intra-individual variability by a simple
      empirical demonstration. Person-specific non-shared environmental influences on
      intra-individual variability of daily school feelings were estimated using time
      series data from twenty-one pairs of monozygotic twins (age = 10 years, 16 female
      pairs) over two consecutive weeks. Results showed substantial inter-individual
      heterogeneity in person-specific non-shared environmental influences. The current
      study represents a first step in investigating environmental influences on intra
      individual variability with an idiographic approach, and provides implications
      for future behavioural genetic studies to examine developmental processes from a
      microscopic angle. 

PMID- 27040687
TI  - Posttraumatic Growth After Motor Vehicle Crashes.
AB  - The relationship between sub-dimensions of posttraumatic growth (PTG) and
      distress was investigated for survivors of motor vehicle crashes (MVC). PTG and
      symptoms of posttraumatic stress disorder (PTSD) for 1045 MVC survivors who
      attended the Accident and Emergency Services were examined with the Chinese
      versions of the Posttraumatic Growth Inventory (PTGI) and the Impact of Event
      Scale-Revised 1 week after the experience of a MVC. A factor structure, which was
      different from both the original English version of the PTGI and the Chinese
      version of PTGI for cancer survivors, was identified. Factors extracted were: (1)
      Life and Self Appreciation; (2) New Commitments; (3) Enlightenment; and (4)
      Relating to Others. However, correlation analyses indicated a functional
      similarity between factors from this study and those from previous studies.
      Relations between PTG sub-dimensions and PTSD symptoms were identified. Results
      from hierarchical multiple regression analysis and structural equation modeling
      show that there were different predictors for different PTG sub-dimensions.
      Findings suggest that different modes of relationship between PTSD symptoms and
      PTG sub-dimensions may co-exist.

PMID- 27040688
TI  - Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger
      Axonal Neuropathy.
AB  - Abnormal protein aggregation is observed in an expanding number of
      neurodegenerative diseases. Here, we describe a mechanism for intracellular toxic
      protein aggregation induced by an unusual mutation event in families affected by
      axonal neuropathy. These families carry distinct frameshift variants in NEFH
      (neurofilament heavy), leading to a loss of the terminating codon and translation
      of the 3' UTR into an extra 40 amino acids. In silico aggregation prediction
      suggested the terminal 20 residues of the altered NEFH to be amyloidogenic, which
      we confirmed experimentally by serial deletion analysis. The presence of this
      amyloidogenic motif fused to NEFH caused prominent and toxic protein aggregates
      in transfected cells and disrupted motor neurons in zebrafish. We identified a
      similar aggregation-inducing mechanism in NEFL (neurofilament light) and FUS
      (fused in sarcoma), in which mutations are known to cause aggregation in Charcot
      Marie-Tooth disease and amyotrophic lateral sclerosis, respectively. In summary,
      we present a protein-aggregation-triggering mechanism that should be taken into
      consideration during the evaluation of stop-loss variants. 

PMID- 27040689
TI  - Imputing Gene Expression in Uncollected Tissues Within and Beyond GTEx.
AB  - Gene expression and its regulation can vary substantially across tissue types. In
      order to generate knowledge about gene expression in human tissues, the Genotype
      Tissue Expression (GTEx) program has collected transcriptome data in a wide
      variety of tissue types from post-mortem donors. However, many tissue types are
      difficult to access and are not collected in every GTEx individual. Furthermore,
      in non-GTEx studies, the accessibility of certain tissue types greatly limits the
      feasibility and scale of studies of multi-tissue expression. In this work, we
      developed multi-tissue imputation methods to impute gene expression in
      uncollected or inaccessible tissues. Via simulation studies, we showed that the
      proposed methods outperform existing imputation methods in multi-tissue
      expression imputation and that incorporating imputed expression data can improve
      power to detect phenotype-expression correlations. By analyzing data from nine
      selected tissue types in the GTEx pilot project, we demonstrated that harnessing
      expression quantitative trait loci (eQTLs) and tissue-tissue expression-level
      correlations can aid imputation of transcriptome data from uncollected GTEx
      tissues. More importantly, we showed that by using GTEx data as a reference, one
      can impute expression levels in inaccessible tissues in non-GTEx expression
      studies. 

PMID- 27040691
TI  - Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable
      Syndrome of Intellectual Disability and Hypotonia.
AB  - Through an international multi-center collaboration, 13 individuals from nine
      unrelated families and affected by likely pathogenic biallelic variants in TBC1
      domain-containing kinase (TBCK) were identified through whole-exome sequencing.
      All affected individuals were found to share a core phenotype of intellectual
      disability and hypotonia, and many had seizures and showed brain atrophy and
      white-matter changes on neuroimaging. Minor non-specific facial dysmorphism was
      also noted in some individuals, including multiple older children who developed
      coarse features similar to those of storage disorders. TBCK has been shown to
      regulate the mammalian target of rapamycin (mTOR) signaling pathway, which is
      also stimulated by exogenous leucine supplementation. TBCK was absent in cells
      from affected individuals, and decreased phosphorylation of phospho-ribosomal
      protein S6 was also observed, a finding suggestive of downregulation of mTOR
      signaling. Lastly, we demonstrated that activation of the mTOR pathway in
      response to L-leucine supplementation was retained, suggesting a possible avenue
      for directed therapies for this condition. 

PMID- 27040690
TI  - DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide
      Consortium Meta-analysis.
AB  - Epigenetic modifications, including DNA methylation, represent a potential
      mechanism for environmental impacts on human disease. Maternal smoking in
      pregnancy remains an important public health problem that impacts child health in
      a myriad of ways and has potential lifelong consequences. The mechanisms are
      largely unknown, but epigenetics most likely plays a role. We formed the
      Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across
      13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and
      newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the
      Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in
      relation to maternal smoking at genome-wide statistical significance (false
      discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not
      previously related to smoking and methylation in either newborns or adults.
      Several genes are relevant to diseases that can be caused by maternal smoking
      (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A
      number of differentially methylated CpGs were associated with gene expression. We
      observed enrichment in pathways and processes critical to development. In older
      children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of
      significance, far more than expected by chance (p value < 2.2 * 10(-16)). Results
      were robust to different normalization methods used across studies and cell type
      adjustment. In this large scale meta-analysis of methylation data, we identified
      numerous loci involved in response to maternal smoking in pregnancy with
      persistence into later childhood and provide insights into mechanisms underlying
      effects of this important exposure. 

PMID- 27040692
TI  - Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating
      Protein, Cause Severe Infantile Syndromic Encephalopathy.
AB  - Infantile encephalopathies are a group of clinically and biologically
      heterogeneous disorders for which the genetic basis remains largely unknown.
      Here, we report a syndromic neonatal encephalopathy characterized by profound
      developmental disability, severe hypotonia, seizures, diminished respiratory
      drive requiring mechanical ventilation, brain atrophy, dysgenesis of the corpus
      callosum, cerebellar vermis hypoplasia, and facial dysmorphism. Biallelic
      inactivating mutations in TBCK (TBC1-domain-containing kinase) were independently
      identified by whole-exome sequencing as the cause of this condition in four
      unrelated families. Matching these families was facilitated by the sharing of
      phenotypic profiles and WES data in a recently released web-based tool (Geno2MP)
      that links phenotypic information to rare variants in families with Mendelian
      traits. TBCK is a putative GTPase-activating protein (GAP) for small GTPases of
      the Rab family and has been shown to control cell growth and proliferation, actin
      cytoskeleton dynamics, and mTOR signaling. Two of the three mutations (c.376C>T
      [p.Arg126(*)] and c.1363A>T [p.Lys455(*)]) are predicted to truncate the protein,
      and loss of the major TBCK isoform was confirmed in primary fibroblasts from one
      affected individual. The third mutation, c.1532G>A (p.Arg511His), alters a
      conserved residue within the TBC1 domain. Structural analysis implicated Arg511
      as a required residue for Rab-GAP function, and in silico homology modeling
      predicted impaired GAP function in the corresponding mutant. These results
      suggest that loss of Rab-GAP activity is the underlying mechanism of disease. In
      contrast to other disorders caused by dysregulated mTOR signaling associated with
      focal or global brain overgrowth, impaired TBCK function results in progressive
      loss of brain volume. 

PMID- 27040693
TI  - Early phase interference between low-intensity running and power training in
      moderately trained females.
AB  - PURPOSE: The aim of the study was to investigate the effects of low-intensity
      running performed immediately after lower-body power-training sessions on power
      development. METHODS: Twenty young females participated in 6 weeks, 3/week, of
      either lower body power training (PT) or lower body power training followed by 30
      min of low-intensity running (PET) eliciting 60-70 % of maximal heart rate. The
      following were measured before and after the training period: counter-movement
      jump, isometric leg press force and rate of force development (RFD), half squat 1
      RM, vastus lateralis fiber type composition and cross sectional area, resting
      intramuscular fiber conduction velocity (MFCV), and heart rate during the
      modified Bruce treadmill test. RESULTS: Counter-movement jump height and peak
      power increased after PT (10.7 +/- 6.2 and 12.9 +/- 18.7 %, p < 0.05) but not
      after PET (3.4 +/- 7.6 and 5.11 +/- 10.94 %, p > 0.05). Maximum isometric force,
      RFD, and half squat 1-RM increased similarly in both groups. Muscle fiber type
      composition was not altered in either group. Muscle fiber cross sectional area
      increased only after PT (17.5 +/- 17.4, 14.5 +/- 10.4, 20.36 +/- 11.3 %, in type
      I, IIA, and IIX fibers, respectively, p < 0.05). Likewise, mean MFCV increased
      with PT only (before: 4.53 +/- 0.38 m s(-1), after: 5.09 +/- 0.39 m s(-1), p =
      0.027). Submaximal heart rate during the Bruce treadmill test remained unchanged
      after PT but decreased after PET. CONCLUSION: These results suggest that low
      intensity running performed after lower-body power training impairs the exercise
      induced adaptation in stretch-shortening cycle jumping performance (vertical jump
      height, peak power), during the first 6 weeks of training, which may be partially
      linked to inhibited muscle fiber hypertrophy and muscle fiber conduction
      velocity.

PMID- 27040694
TI  - Changes in water and sugar-containing beverage consumption and body weight
      outcomes in children.
AB  - An intervention study showed that promoting water consumption in schoolchildren
      prevented overweight, but a mechanism linking water consumption to overweight was
      not substantiated. We investigated whether increased water consumption replaced
      sugar-containing beverages and whether changes in water or sugar-containing
      beverages influenced body weight outcomes. In a secondary analysis of the
      intervention study in Germany, we analysed combined longitudinal data from the
      intervention and control groups. Body weight and height were measured and
      beverage consumption was self-reported by a 24-h recall questionnaire at the
      beginning and end of the school year 2006/2007. The effect of a change in water
      consumption on change in sugar-containing beverage (soft drinks and juices)
      consumption, change in BMI (kg/m2) and prevalence of overweight and obesity at
      follow-up was analysed using regression analyses. Of 3220 enroled children, 1987
      children (mean age 8.3 (sd 0.7) years) from thirty-two schools were analysed.
      Increased water consumption by 1 glass/d was associated with a reduced
      consumption of sugar-containing beverages by 0.12 glasses/d (95 % CI -0.16, 
      0.08) but was not associated with changes in BMI (P=0.63). Increased consumption
      of sugar-containing beverages by 1 glass/d was associated with an increased BMI
      by 0.02 (95 % CI 0.00, 0.03) kg/m2 and increased prevalence of obesity (OR 1.22;
      95 % CI 1.04, 1.44) but not with overweight (P=0.83). In conclusion, an increase
      in water consumption can replace sugar-containing beverages. As sugar-containing
      beverages were associated with weight gain, this replacement might explain the
      prevention of obesity through the promotion of water consumption.

PMID- 27040695
TI  - Dissecting functions of the N-terminal domain and GAS-site recognition in STAT3
      nuclear trafficking.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a ubiquitous
      transcription factor involved in many biological processes, including
      hematopoiesis, inflammation and cancer progression. Cytokine-induced gene
      transcription greatly depends on tyrosine phosphorylation of STAT3 on a single
      tyrosine residue with subsequent nuclear accumulation and specific DNA sequence
      (GAS) recognition. In this study, we analyzed the roles of the conserved STAT3 N
      terminal domain (NTD) and GAS-element binding ability of STAT3 in
      nucleocytoplasmic trafficking. Our results demonstrate the nonessential role of
      GAS-element recognition for both cytokine-induced and basal nuclear import of
      STAT3. Substitution of five key amino acids within the DNA-binding domain
      rendered STAT3 unable to bind to GAS-elements while still maintaining the ability
      for nuclear localization. In turn, deletion of the NTD markedly decreased nuclear
      accumulation upon IL-6 treatment resulting in a prolonged accumulation of
      phosphorylated dimers in the cytoplasm, at the same time preserving specific DNA
      recognition ability of the truncation mutant. Observed defect in nuclear
      localization could not be explained by flawed importin-alpha binding, since both
      wild-type and NTD deletion mutant of STAT3 could precipitate both full-length and
      autoinhibitory domain (?IBB) deletion mutants of importin-alpha5, as well as ?IBB
      alpha3 and ?IBB-alpha7 isoforms independently of IL-6 stimulation. Despite its
      inability to translocate to the nucleus upon IL-6 stimulation, the NTD lacking
      mutant still showed nuclear accumulation in resting cells similar to wild-type
      upon inhibition of nuclear export by leptomycin B. At the same time, blocking the
      nuclear export pathway could not rescue cytoplasmic trapping of phosphorylated
      STAT3 molecules without NTD. Moreover, STAT3 mutant with dysfunctional SH2 domain
      (R609Q) also localized in the nucleus of unstimulated cells after nuclear export
      blocking, while upon cytokine treatment the subcellular localization of this
      mutant had not changed. Our findings support the concept that basal
      nucleocytoplasmic shuttling of STAT3 is different from active cytokine-induced
      nuclear import and does not require conserved N- or SH2-terminal domains,
      preformed dimer formation and GAS-element-specific DNA recognition.

PMID- 27040696
TI  - Chronic lymphocytic leukemia: recent progress and current challenges.

PMID- 27040697
TI  - What does it mean I have a monoclonal B-cell lymphocytosis?: Recent insights and
      new challenges.
AB  - Monoclonal B-cell lymphocytosis (MBL) is defined as a laboratory abnormality
      where small (<5 x 10(9)/L) clonal B-cell populations are detected in the
      peripheral blood of otherwise healthy subjects. According to the immunophenotype,
      MBL is labeled as chronic lymphocytic leukemia (CLL)-like (75% of cases),
      atypical CLL, and CD5-negative. Concentration of clonal B cells differentiates
      low- (LC) and high-count (HC)-MBL (< or >= 0.5 x 10(9)/L, respectively). Thanks
      to technical improvements, we are able to identify CLL-like clonal B-cell
      populations at increased frequency with age, but we are still far from
      understanding its relationship with clinically overt CLL. LC-MBL, requiring high
      throughput screening technique to be identified in population studies, seems to
      be a bird of a different feather and several hints suggest that LC-MBL is related
      to aging and/or chronic antigenic stimulation. Immunogenetic, cytogenetic and
      genetic data support the notion that HC-MBL, usually identified in the clinical
      setting, is a premalignant condition and, based on biological parameters, it is
      frequently difficult to differentiate it from early stage CLL. The rapid
      improvement and widespread availability of cutting-edge technology, in particular
      next-generation sequencing (NGS), raises hope that we are getting closer to
      unveiling the fundamental nature of MBL and CLL and how they are related to each
      other. 

PMID- 27040699
TI  - Gene mutations in chronic lymphocytic leukemia.
AB  - The recent discovery of genes mutated in chronic lymphocytic leukemia (CLL) has
      stimulated new research into the role of these genes in CLL pathogenesis. CLL
      cases carry approximately 5-20 mutated genes per exome, a lower number than
      detected in many human tumors. Of the recurrently mutated genes in CLL, all are
      mutated in 10% or less of patients when assayed in unselected CLL cohorts at
      diagnosis. Mutations in TP53 are of major clinical relevance, are often
      associated with del17p and gain in frequency over time. TP53 mutated and
      associated del17p states substantially lower response rates, remission duration,
      and survival in CLL. Mutations in NOTCH1 and SF3B1 are recurrent, often
      associated with progressive CLL that is also IgVH unmutated and ZAP70-positive
      and are under investigation as targets for novel therapies and as factors
      influencing CLL outcome. There are an estimated 20-50 additional mutated genes
      with frequencies of 1%-5% in CLL; more work is needed to identify these and to
      study their significance. Finally, of the major biological aberration categories
      influencing CLL as a disease, gene mutations will need to be placed into context
      with regard to their ultimate role and importance. Such calibrated appreciation
      necessitates studies incorporating multiple CLL driver aberrations into
      biological and clinical analyses. 

PMID- 27040698
TI  - MicroRNAs in chronic lymphocytic leukemia: miRacle or miRage for prognosis and
      targeted therapies?
AB  - Chronic lymphocytic leukemia (CLL) is a heterogeneous disease and has a highly
      variable clinical course with survival ranging from a couple of months to several
      decades. MicroRNAs (miRNAs), small non-coding RNAs that regulate transcription
      and translation of genes, have been found to be involved in CLL initiation,
      progression, and resistance to therapy. In addition, they can be used as
      prognostic biomarkers and as targets for novel therapies. In this review, we
      describe the association between miRNAs and the cytogenetic aberrations commonly
      found in CLL, as well as with other prognostic factors. We describe the presence
      of miRNAs as extracellular entities in the plasma and serum of CLL patients and
      discuss their role in resistance to therapy. Finally, we will explore the
      potential of targeted miRNA therapy for the treatment of CLL, with a special
      emphasis on MRX34, the first miRNA mimic that is currently being evaluated for
      clinical use. 

PMID- 27040700
TI  - Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the
      tools of the trade.
AB  - In the last decade our understanding of chronic lymphocytic leukemia (CLL)
      biology and pathogenesis has increased substantially. These insights have led to
      the development of several new agents with novel mechanisms of action prompting a
      change in therapeutic approaches from chemotherapy-based treatments to targeted
      therapies. Multiple preclinical models for drug development in CLL are available;
      however, with the advent of these targeted agents, it is becoming clear that not
      all models and surrogate readouts of efficacy are appropriate for all drugs. In
      this review we discuss in vitro and in vivo preclinical models, with a particular
      focus on the benefits and possible pitfalls of different model systems in the
      evaluation of novel therapeutics for the treatment of CLL. 

PMID- 27040701
TI  - Prognostic factors and risk stratification in chronic lymphocytic leukemia.
AB  - There is considerable heterogeneity in the clinical outcome of patients with
      chronic lymphocytic leukemia (CLL). While some patients live for decades without
      any therapy, others die within years of diagnosis despite multiple treatments. To
      better counsel newly diagnosed CLL patients about their disease course, the Rai
      and Binet staging systems were developed four decades ago. A deeper understanding
      of the biologic and molecular aberrations contributing to the pathogenesis of CLL
      led to identification of novel prognostic markers such as immunoglobulin heavy
      chain variable gene (IGHV) mutation status, leukemia-cell expression of CD38, ZAP
      70, and CD49d, and cytogenetic abnormalities detected by fluorescent in situ
      hybridization (FISH). The advent of next-generation sequencing has provided
      unprecedented insights into the subclonal architecture of CLL and its impact on
      disease progression and survival. More recently, integrated prognostic scoring
      systems that incorporate clinical, biologic and genetic characteristics into a
      single risk score have been developed and appear to improve the accuracy of
      prognostication for individual patients. This review summarizes the state-of-the
      art prognostic factors and will guide the practicing clinician in their care of
      patients with CLL. 

PMID- 27040702
TI  - Initial therapy of chronic lymphocytic leukemia.
AB  - Only chronic lymphocytic leukemia (CLL) patients with active or symptomatic
      disease or with advanced Binet or Rai stages require therapy. Prognostic risk
      factor profile and comorbidity burden are most relevant for the choice of
      treatment. For physically fit patients, chemoimmunotherapy with fludarabine,
      cyclophosphamide, and rituximab remains the current standard therapy. For unfit
      patients, treatment with an anti-CD20 antibody (obinutuzumab or rituximab or
      ofatumumab) plus milder chemotherapy (chlorambucil) may be applied. Patients with
      a del(17p) or TP53 mutation should be treated with the kinase inhibitors
      ibrutinib or a combination of idelalisib and rituximab. Clinical trials over the
      next several years will determine, whether kinase inhibitors, other small
      molecules, immunotherapeutics, or combinations thereof will further improve
      outcomes for patients with CLL. 

PMID- 27040703
TI  - Bruton tyrosine kinase inhibition in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and remains
      incurable outside of the setting of allogeneic stem cell transplant. While the
      standard therapy for both initial and relapsed CLL has traditionally included
      monoclonal antibody therapy in combination with chemotherapy, there are patients
      with high-risk disease features including unmutated IgVH, del(11q22) and
      del(17p13) that are associated with poor overall responses to these therapies
      with short time to relapse and shortened overall survival. Additionally, many of
      these therapies have a high rate of infectious toxicity in a population already
      at increased risk. Targeting the B-cell receptor (BCR) signaling pathway has
      emerged as a promising therapeutic advance in a variety of B-cell malignancies,
      including CLL. Bruton agammaglobulinemia tyrosine kinase (Btk) is a tyrosine
      kinase in the BCR pathway critical to the survival of both normal and malignant B
      cells and inhibition of this kinase has shown to block the progression of CLL.
      Ibrutinib, a first in class oral inhibitor of Btk, has shown promise as a very
      effective agent in the treatment of CLL-in both relapsed and upfront therapy,
      alone and in combination with other therapies, and in patients of all-risk
      disease-which has led to its approval in relapsed CLL and as frontline therapy in
      patients with the high-risk del(17p13) disease. Several studies are ongoing to
      evaluate the efficacy and safety of ibrutinib in combination with chemotherapy as
      frontline treatment for CLL and investigation into newer-generation Btk
      inhibitors is also underway. 

PMID- 27040704
TI  - The PI3K pathway: clinical inhibition in chronic lymphocytic leukemia.
AB  - Constitutive or mutational activation of the phosphatidylinositol 3 kinase, or
      PI3K, has been implicated in many cancers, including chronic lymphocytic leukemia
      (CLL). The delta isoform of the p110 catalytic subunit of PI3K has its primary
      physiologic function in B cells and appears to be the predominant mediator of
      most PI3K signals in CLL cells. Idelalisib is a first-in-class inhibitor of the
      PI3K delta isoform that shows near complete inhibition of AKT phosphorylation in
      CLL cells in vitro and in vivo. Idelalisib shows the classic pattern of response
      to BCR inhibition in CLL, with rapid nodal response and transient increase in
      lymphocytosis. The phase I study established the recommended dose as 150 mg twice
      per day. Subsequent registration trials have focused predominantly on antibody
      combinations, leading to the US Food and Drug Administration (FDA) approval of
      idelalisib with rituximab for relapsed CLL patients for whom rituximab is
      appropriate therapy in summer 2014. The median progression-free survival (PFS) of
      idelalisib-rituximab in this heavily pretreated CLL population with multiple
      comorbidities and frequent 17p deletion was an impressive 19.4 months. The
      success of idelalisib has paved the way for the development of other PI3K
      inhibitors in CLL, including duvelisib and TGR-1202, which are in or moving
      toward registration trials. 

PMID- 27040705
TI  - Cyclin-dependent kinase inhibitors for the treatment of chronic lymphocytic
      leukemia.
AB  - In the last 10 years, oncology has been transformed by the development and broad
      availability of small molecule therapies for cancer. Compounds have been and are
      being developed to target nearly every known relevant component of the cell's
      machinery. One class of compounds, the cyclin-dependent kinase (CDK) inhibitors,
      was originally conceived as an anticancer therapeutic based on the premise that
      as cancer is (in part) defined by loss of cell-cycle control, the interruption of
      cell cycle could arrest cancer growth. While CDKs do play critical roles in cell
      cycle, including in cancer, the study of CDK inhibitors in the relatively non
      proliferative disease chronic lymphocytic leukemia (CLL) revealed alternate
      mechanisms both for CDKs, as well as for the role of CDK inhibitors in cancer
      therapy. In this review, we will consider three CDK inhibitors: alvocidib
      (flavopiridol), dinaciclib, and TG02. We will discuss their preclinical and
      clinical development for the treatment of CLL, and suggest that CDK inhibitors
      remain relevant in CLL, with potential utility in several scenarios. 

PMID- 27040706
TI  - Progress in BCL2 inhibition for patients with chronic lymphocytic leukemia.
AB  - The prosurvival protein BCL2 is uniformly expressed in chronic lymphocytic
      leukemia (CLL), and enables leukemia cell survival in the face of cytotoxic
      treatment and increasing genomic, metabolic, and oxidative stresses. The
      therapeutic potential of BCL2 inhibition was first observed in the clinic
      following BCL2 antisense therapy. Subsequently, a number of small molecule
      inhibitors were developed to mimic the function of the pro-apoptotic BH3-only
      proteins (BH3-mimetics). These molecules are now in late-phase clinical trials
      and demonstrate potent activity, including the occurrence of acute tumor lysis
      syndrome in subjects with multiply relapsed, chemorefractory CLL. In this review,
      we discuss the history and summarize current knowledge regarding BCL2 inhibition
      as therapy of CLL. 

PMID- 27040707
TI  - Antibody therapy alone and in combination with targeted drugs in chronic
      lymphocytic leukemia.
AB  - The development of non-chemotherapeutic agents, including monoclonal antibodies
      (mAbs) and other targeted drugs, makes chemotherapy-free treatment an attractive
      option for chronic lymphocytic leukemia (CLL). The classical mAb, rituximab, has
      been authorized for use in both first-line and second-line therapy for CLL. New
      mAbs directed against CD20, ofatumumab, and obinutuzumab (GA-101) have also been
      approved for the treatment of this disease. Recently, several new mAbs with
      potential benefits over the approved anti-CD20 antibodies have been developed for
      use in CLL. Anti-CD37, anti-CD19, and anti-CD40 mAbs are in early clinical trials
      and show promise in treating CLL. In addition, the combination of mAbs with B
      cell receptor signaling pathway inhibitors and immunomodulatory drugs makes the
      chemotherapy-free option a reality today. Combinations of antibodies with
      targeted drugs like ibrutinib, idelalisib, or lenalidomide are expected to
      replace chemotherapy-based combinations for treating CLL in the near future.
      However, phase III trials should confirm the benefit of these new treatment
      strategies and establish their exact place in the therapeutic armamentarium for
      CLL. 

PMID- 27040709
TI  - Secondary autoimmune cytopenias in chronic lymphocytic leukemia.
AB  - Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct
      clinical entities that require specific management. These autoimmune disorders
      have a complex pathogenesis that involves both the leukemic cells and the immune
      environment in which they exist. The mechanism is not the same in all cases, and
      to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in
      antibody production, antigen presentation, and stimulation of T cells and
      bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be
      challenging as it is difficult to differentiate between autoimmunity and bone
      marrow failure due to disease progression. There is a need to distinguish these
      causes, as prognosis and treatment are not the same. Evidence regarding treatment
      of secondary autoimmune cytopenias is limited, but many effective options exist
      and treatment can be selected with severity of disease and patient factors in
      mind. With new agents to treat CLL coming into widespread clinical use, it will
      be important to understand how these will change the natural history and
      treatment of autoimmune cytopenias. 

PMID- 27040708
TI  - Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor
      T cells.
AB  - Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia
      (CLL) has heralded a new era of synthetic biology. The infusion of genetically
      engineered, autologous chimeric antigen receptor (CAR) T cells directed against
      CD19 expressed by normal and malignant B cells represents a novel approach to
      cancer therapy. The results of recent clinical trials of CAR T cells in relapsed
      and refractory CLL have demonstrated long-term disease-free remissions,
      underscoring the power of harnessing and redirecting the immune system against
      cancer. This review will briefly summarize T-cell therapies in development for
      CLL disease. We discuss the role of T-cell function and phenotype, T-cell culture
      optimization, CAR design, and approaches to potentiate the survival and anti
      tumor effects of infused lymphocytes. Future efforts will focus on improving the
      efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell
      immunotherapy into standard medical management of CLL. 

PMID- 27040710
TI  - Richter syndrome: pathogenesis and management.
AB  - Richter syndrome (RS) is the development of an aggressive lymphoma in patients
      with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL).
      The incidence rate RS is ~0.5% per year of observation. Two biomarkers (NOTCH1
      mutations and subset 8 configuration of the B-cell receptor) may help identifying
      CLL patients at risk of RS to be considered for close monitoring and a careful
      biopsy policy. In the presence of clinical features suspicious of RS, diagnosis
      of transformation and choice of the site of biopsy may take advantage of fluorine
      18 fluorodeoxyglucose ((18)FDG) positron emission tomography (PET)/computed
      tomography (CT). Molecular lesions of regulators of tumor suppression (TP53),
      cell cycle (CDKN2A), and cell proliferation (NOTCH1, MYC) overall account for
      ~90% of RS and may be responsible for the aggressive clinical phenotype observed
      in this disease because of the combined effect of chemoresistance and rapid
      disease kinetics. The prognosis of RS is generally highly unfavorable. However,
      the pattern of survival is not homogeneous and the most important prognostic
      factor is the clonal relationship between the CLL and the aggressive lymphoma
      clones. Rituximab-containing polychemotherapy represents the backbone for
      induction treatment in RS. Younger patients who respond to induction therapy
      should be offered stem cell transplant (SCT) to prolong survival. 

PMID- 27040711
TI  - Carnosine decreased neuronal cell death through targeting glutamate system and
      astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to
      OGD/recovery.
AB  - Previously, we showed that carnosine upregulated the expression level of
      glutamate transporter 1 (GLT-1), which has been recognized as an important
      participant in the astrocyte-neuron lactate shuttle (ANLS), with ischemic model
      in vitro and in vivo. This study was designed to investigate the protective
      effect of carnosine on neuron/astrocyte co-cultures exposed to OGD/recovery, and
      to explore whether the ANLS or any other mechanism contributes to carnosine
      induced neuroprotection on neuron/astrocyte. Co-cultures were treated with
      carnosine and exposed to OGD/recovery. Cell death and the extracellular levels of
      glutamate and GABA were measured. The mitochondrial respiration and glycolysis
      were detected by Seahorse Bioscience XF96 Extracellular Flux Analyzer. Results
      showed that carnosine decreased neuronal cell death, increased extracellular GABA
      level, and abolished the increase in extracellular glutamate and reversed the
      mitochondrial energy metabolism disorder induced by OGD/recovery. Carnosine also
      upregulated the mRNA level of neuronal glutamate transporter EAAC1 at 2h after
      OGD. Dihydrokainate, a specific inhibitor of GLT-1, decreased glycolysis but it
      did not affect mitochondrial respiration of the cells, and it could not reverse
      the increase in mitochondrial OXPHOS induced by carnosine in the co-cultures. The
      levels of mRNAs for monocarboxylate transporter1, 4 (MCT1, 4), which were
      expressed in astrocytes, and MCT2, the main neuronal MCT, were significantly
      increased at the early stage of recovery. Carnosine only partly reversed the
      increased expression of astrocytic MCT1 and MCT4. These results suggest that
      regulating astrocytic energy metabolism and extracellular glutamate and GABA
      levels but not the ANLS are involved in the carnosine-induced neuroprotection.

PMID- 27040712
TI  - Platelet-activating factor receptor (PAFR) plays a crucial role in experimental
      global cerebral ischemia and reperfusion.
AB  - Stroke is one of the most frequent causes of death and disability worldwide
      leading to a significant clinical and socioeconomic burden. Although different
      mechanisms are involved in the pathogenesis of stroke, inflammatory response
      occurs after ischemia and contributes to the expansion of brain injury. Platelet
      activating factor receptor (PAF) plays crucial roles in both physiological and
      pathological conditions in the brain. PAF receptor (PAFR) may be expressed on
      cellular and nuclear membranes of various cell types, especially leukocytes,
      platelets, endothelial cells, neuronal cells and microglia. Herein, using mice
      lacking the PAFR receptor (PAFR(-/-)), we investigate a potential role for this
      receptor during experimental transient global cerebral ischemia and reperfusion
      (BCCAo). In PAFR deficiency, we observed a significant improvement in the
      neurological deficits, which were associated with a reduction of brain infarcted
      area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, a decrease in
      the percentage of necrotic cavities areas and in the frequency of ischemic
      neurons was also found by employing histometric analysis. In addition, in PAFR(-/
      ) mice there was prevention of caspase-3 activation and decreased vascular
      permeability and brain edema. Decreased brain levels of the cytokines tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine
      (C-X-C motif) ligand 1 (CXCL1) by ELISA were also detected in PAFR(-/-) BCCAo
      animals. Taken together, our results suggest that PAFR activation might be
      crucial for the global brain ischemia and reperfusion injury.

PMID- 27040713
TI  - Comparative power spectrum analysis of EEG activity in spontaneously hypertensive
      and Wistar rats in kainate model of temporal model of epilepsy.
AB  - Recently, we have reported that spontaneously hypertensive rats (SHRs) exhibit
      higher susceptibility than Wistar rats in kainate (KA) model of epilepsy. The aim
      of the present study is to compare the baseline of EEG signals in SHRs and Wistar
      rats using Discrete Fourier transform (DFT) during the three phases of KA model
      (acute, latent and chronic). The SHRs showed higher baseline relative power of
      delta waves in the left frontal cortex and lower gamma-HF waves in the left
      frontal and left/right parietal cortex, respectively, compared to Wistar rats.
      During the acute phase, both absolute and relative power of fast EEG bands (gamma
      HF) was lower in the left/right frontal and the left/right parietal cortex in
      SHRs compared to Wistar rats. During the latent phase, no difference in the power
      of the investigated bands was detected between the two strains. During the
      chronic epileptic phase, the SHRs were characterized with higher power of HF
      oscillations than Wistar rats both in the frontal and parietal cortex without
      brain lateralization while theta, alpha and beta bands were with diminished power
      in the left parietal cortex of SHRs compared to normotensive Wistar rats. Taken
      together, the presented results suggest that the increased delta waves and lower
      gamma-HF waves in the frontal/parietal cortex are associated with a higher
      seizure susceptibility of SHRs compared to Wistar rats while fastest oscillations
      has a critical role in seizure generation and propagation of hypertensive rats.

PMID- 27040714
TI  - Blockade of 5-HT2A receptors at the site of inflammation inhibits activation of
      spinal dorsal horn neurons in rats.
AB  - Repeated inflammation in the periphery is a major cause of chronic inflammatory
      pain. We have showed that blockade of 5-HT2A receptors in the periphery inhibits
      repeated inflammation-induced pain hypersensitivity. The present study
      investigated whether inhibition of 5-HT2A receptor signaling at the site of
      inflammation could inhibit repeated inflammation-induced neurochemical changes in
      spinal dorsal horn neurons. Treatment with the 5-HT2A receptor antagonist
      ketanserin (20MUg) in the hindpaw following intraplantar injection of carrageenan
      inhibited the increase in nicotinamide adenine dinucleotide phosphate-diaphorase
      (NADPH-d) reactivity, a marker of nitric oxide synthase (NOS), in the spinal
      dorsal horn. Administration of formalin (1%) in the hindpaw following the
      carrageenan injection evoked a great increase in NADPH-d reactivity in spinal
      dorsal horn neurons on the ipsilateral and contralateral sides. These changes
      were abolished by the pretreatment of ketanserin (20MUg). The ketanserin
      treatment also reduced the repeated inflammation-induced expression of protein
      kinase gamma (PKCgamma) in the membrane of spinal dorsal horn neurons and
      increased PKCgamma protein level in the cytosol. Following the treatment with the
      opioid receptor antagonist naloxone methiodide (5mg/kg, s.c.), the administration
      of ketanserin failed to inhibit the repeated inflammation-induced increase in
      NADPH-d reactivity and c-Fos expression in the spinal dorsal horn. These results
      suggest that 5-HT2A receptor bioactivity in the inflammatory site plays an
      important role in repeated inflammation-induced central sensitization. The
      present study supports the notion that targeting 5-HT2A receptors in the
      periphery can be a promising therapy for relieving chronic inflammatory pain.

PMID- 27040715
TI  - Seroprevalence of antibodies to Rickettsia typhi in the Waikato region of New
      Zealand.
AB  - The first reported New Zealand-acquired case of murine typhus occurred near
      Auckland in 1989. Since then, 72 locally acquired cases have been recorded from
      northern New Zealand. By 2008, on the basis of the timing and distribution of
      cases, it appeared that murine typhus was escalating and spreading southwards. To
      explore the presence of Rickettsia typhi in the Waikato region, we conducted a
      seroprevalence study, using indirect immunofluorescence, Western blot, and cross
      adsorption assays of blood donor samples. Of 950 human sera from Waikato, 12
      (1.3%) had R. typhi antibodies. The seroprevalence for R. typhi was slightly
      higher in northern Waikato (1.4%) compared to the south (1.2%; no significant
      difference, chi 2 P = 0.768 at P < 0.05). Our results extend the reported
      southern range of R. typhi by 140 km and indicate it is endemic in Waikato.
      Evidence of past Rickettsia felis infections was also detected in six sera.
      Globally, R. felis is an emerging disease of concern and this pathogen should
      also be considered when locally acquired rickettsiosis is suspected. If public
      health interventions are to be implemented to reduce the risk of rickettsioses as
      a significant public health problem, improvements in rickettsial diagnostics and
      surveillance will be necessary.

PMID- 27040716
TI  - Editorial for the Virtual Issue on Photochemistry and Photophysics of Lanthanide
      Compounds.

PMID- 27040717
TI  - Encapsulating Naphthalene in an Electron-Deficient MOF to Enhance Fluorescence
      for Organic Amines Sensing.
AB  - Host-guest encapsulation of electron-rich naphthalene molecules into a weakly
      emissive porous metal-organic framework based on pi-electron-deficient (pi
      acidic) naphthalene diimide tectons leads to orange-emissive crystals, which can
      be used to sense strongly basic organic amines in a fast response, high
      photostability, and tunable sensitivity. Moreover, such host-guest inclusion
      crystals are also a good photochromic probe for the detection of weakly basic N
      methyl-2-pyrrolidone and N,N-dimethylformamide molecules. 

PMID- 27040718
TI  - Silver(I)-Catalyzed Atroposelective Desymmetrization of N-Arylmaleimide via 1,3
      Dipolar Cycloaddition of Azomethine Ylides: Access to Octahydropyrrolo[3,4
      c]pyrrole Derivatives.
AB  - A highly efficient Ag(I)-catalyzed atroposelective desymmetrization of N-(2-t
      butylphenyl)maleimide via 1,3-dipolar cycloaddition of in situ generated
      azomethine ylides has been established successfully, affording a facile access to
      a series of biologically important and enantioenriched octahydropyrrolo[3,4
      c]pyrrole derivatives in generally high yields (up to 99%) with excellent levels
      of diastereo-/enantioselectivities (up to 99% ee, >20:1 dr). Subsequent
      transformations led to fascinating 2H-pyrrole and polysubstituted pyrrole
      compounds without loss of stereoselectivity. The absolute configuration of the
      generated chiral axis has been unambiguously identified as (M) through single
      crystal X-ray diffraction analysis. Furthermore, on the basis of the
      comprehensive experimental results and the absolute configuration of one of the
      cycloadducts, the origin of the stereoselectivity was proposed to be attributed
      to the steric congestion imposed by the bulky PPh2 group of the chiral ligand and
      the tert-butyl group of N-(2-t-butylphenyl)maleimide. The possible hydrogen bond
      interaction between the NH2 group of the chiral ligand and one of the carbonyl
      groups of N-(2-t-butylphenyl)maleimide is considered to facilitate stabilizing
      the transition state.

PMID- 27040719
TI  - Longitudinal Associations Between the Quality of Mother-Infant Interactions and
      Brain Development Across Infancy.
AB  - The aim of this study was to investigate if normative variations in parenting
      relate to brain development among typically developing children. A sample of 352
      mother-infant dyads came to the laboratory when infants were 5, 10, and 24 months
      of age (final N = 215). At each visit, child resting electroencephalography (EEG)
      was recorded. Mother-infant interactions were videotaped at the 5-month visit.
      The results indicated that higher quality maternal behavior during mother-infant
      interactions predicted higher frontal resting EEG power at 10 and 24 months, as
      well as increases in power between 5 and 10 months, and between 10 and 24 months.
      These findings provide rare support for the hypothesis that normative variation
      in parenting quality may contribute to brain development among typically
      developing infants.

PMID- 27040720
TI  - The predictive skill of species distribution models for plankton in a changing
      climate.
AB  - Statistical species distribution models (SDMs) are increasingly used to project
      spatial relocations of marine taxa under future climate change scenarios.
      However, tests of their predictive skill in the real-world are rare. Here, we use
      data from the Continuous Plankton Recorder program, one of the longest running
      and most extensive marine biological monitoring programs, to investigate the
      reliability of predicted plankton distributions. We apply three commonly used
      SDMs to 20 representative plankton species, including copepods, diatoms, and
      dinoflagellates, all found in the North Atlantic and adjacent seas. We fit the
      models to decadal subsets of the full (1958-2012) dataset, and then use them to
      predict both forward and backward in time, comparing the model predictions
      against the corresponding observations. The probability of correctly predicting
      presence was low, peaking at 0.5 for copepods, and model skill typically did not
      outperform a null model assuming distributions to be constant in time. The
      predicted prevalence increasingly differed from the observed prevalence for
      predictions with more distance in time from their training dataset. More detailed
      investigations based on four focal species revealed that strong spatial
      variations in skill exist, with the least skill at the edges of the
      distributions, where prevalence is lowest. Furthermore, the scores of traditional
      single-value model performance metrics were contrasting and some implied
      overoptimistic conclusions about model skill. Plankton may be particularly
      challenging to model, due to its short life span and the dispersive effects of
      constant water movements on all spatial scales, however there are few other
      studies against which to compare these results. We conclude that rigorous model
      validation, including comparison against null models, is essential to assess the
      robustness of projections of marine planktonic species under climate change.

PMID- 27040721
TI  - Interventions to prevent misconduct and promote integrity in research and
      publication.
AB  - BACKGROUND: Improper practices and unprofessional conduct in clinical research
      have been shown to waste a significant portion of healthcare funds and harm
      public health. OBJECTIVES: Our objective was to evaluate the effectiveness of
      educational or policy interventions in research integrity or responsible conduct
      of research on the behaviour and attitudes of researchers in health and other
      research areas. SEARCH METHODS: We searched the CENTRAL, MEDLINE, LILACS and
      CINAHL health research bibliographical databases, as well as the Academic Search
      Complete, AGRICOLA, GeoRef, PsycINFO, ERIC, SCOPUS and Web of Science databases.
      We performed the last search on 15 April 2015 and the search was limited to
      articles published between 1990 and 2014, inclusive. We also searched conference
      proceedings and abstracts from research integrity conferences and specialized
      websites. We handsearched 14 journals that regularly publish research integrity
      research. SELECTION CRITERIA: We included studies that measured the effects of
      one or more interventions, i.e. any direct or indirect procedure that may have an
      impact on research integrity and responsible conduct of research in its broadest
      sense, where participants were any stakeholders in research and publication
      processes, from students to policy makers. We included randomized and non
      randomized controlled trials, such as controlled before-and-after studies, with
      comparisons of outcomes in the intervention versus non-intervention group or
      before versus after the intervention. Studies without a control group were not
      included in the review. DATA COLLECTION AND ANALYSIS: We used the standard
      methodological procedures expected by Cochrane. To assess the risk of bias in non
      randomized studies, we used a modified Cochrane tool, in which we used four out
      of six original domains (blinding, incomplete outcome data, selective outcome
      reporting, other sources of bias) and two additional domains (comparability of
      groups and confounding factors). We categorized our primary outcome into the
      following levels: 1) organizational change attributable to intervention, 2)
      behavioural change, 3) acquisition of knowledge/skills and 4) modification of
      attitudes/perceptions. The secondary outcome was participants' reaction to the
      intervention. MAIN RESULTS: Thirty-one studies involving 9571 participants,
      described in 33 articles, met the inclusion criteria. All were published in
      English. Fifteen studies were randomized controlled trials, nine were controlled
      before-and-after studies, four were non-equivalent controlled studies with a
      historical control, one was a non-equivalent controlled study with a post-test
      only and two were non-equivalent controlled studies with pre- and post-test
      findings for the intervention group and post-test for the control group. Twenty
      one studies assessed the effects of interventions related to plagiarism and 10
      studies assessed interventions in research integrity/ethics. Participants
      included undergraduates, postgraduates and academics from a range of research
      disciplines and countries, and the studies assessed different types of
      outcomes.We judged most of the included randomized controlled trials to have a
      high risk of bias in at least one of the assessed domains, and in the case of non
      randomized trials there were no attempts to alleviate the potential biases
      inherent in the non-randomized designs.We identified a range of interventions
      aimed at reducing research misconduct. Most interventions involved some kind of
      training, but methods and content varied greatly and included face-to-face and
      online lectures, interactive online modules, discussion groups, homework and
      practical exercises. Most studies did not use standardized or validated outcome
      measures and it was impossible to synthesize findings from studies with such
      diverse interventions, outcomes and participants. Overall, there is very low
      quality evidence that various methods of training in research integrity had some
      effects on participants' attitudes to ethical issues but minimal (or short-lived)
      effects on their knowledge. Training about plagiarism and paraphrasing had
      varying effects on participants' attitudes towards plagiarism and their
      confidence in avoiding it, but training that included practical exercises
      appeared to be more effective. Training on plagiarism had inconsistent effects on
      participants' knowledge about and ability to recognize plagiarism. Active
      training, particularly if it involved practical exercises or use of text-matching
      software, generally decreased the occurrence of plagiarism although results were
      not consistent. The design of a journal's author contribution form affected the
      truthfulness of information supplied about individuals' contributions and the
      proportion of listed contributors who met authorship criteria. We identified no
      studies testing interventions for outcomes at the organizational level. The
      numbers of events and the magnitude of intervention effects were generally small,
      so the evidence is likely to be imprecise. No adverse effects were reported.
      AUTHORS' CONCLUSIONS: The evidence base relating to interventions to improve
      research integrity is incomplete and the studies that have been done are
      heterogeneous, inappropriate for meta-analyses and their applicability to other
      settings and population is uncertain. Many studies had a high risk of bias
      because of the choice of study design and interventions were often inadequately
      reported. Even when randomized designs were used, findings were difficult to
      generalize. Due to the very low quality of evidence, the effects of training in
      responsible conduct of research on reducing research misconduct are uncertain.
      Low quality evidence indicates that training about plagiarism, especially if it
      involves practical exercises and use of text-matching software, may reduce the
      occurrence of plagiarism.

PMID- 27040722
TI  - The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung
      epithelial cells.
AB  - Cobalt is a toxic metal used in various industrial applications leading to
      adverse lung effects by inhalation. Cobalt is considered a possible human
      carcinogen with the lung being a primary target. However, few studies have
      considered cobalt-induced toxicity in human lung cells, especially normal lung
      epithelial cells. Therefore, in this study, we sought to determine the
      cytotoxicity and genotoxicity of particulate and soluble cobalt in normal primary
      human lung epithelial cells. Cobalt oxide and cobalt chloride were used as
      representative particulate and soluble cobalt compounds, respectively. Exposure
      to both particulate and soluble cobalt induced a concentration-dependent increase
      in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on
      intracellular cobalt ion levels, we found that soluble and particulate cobalt
      induced similar cytotoxicity while soluble cobalt was more genotoxic than
      particulate cobalt. These data indicate that cobalt compounds are cytotoxic and
      genotoxic to human lung epithelial cells.

PMID- 27040724
TI  - Oxygen insertion into boroles as a route to 1,2-oxaborines.
AB  - The synthesis of 1,2-oxaborines is accomplished via the reaction of
      pentaarylboroles with N-methylmorpholine-N-oxide via a 1,1-insertion reaction.
      The aromatic nature of 1,2-oxaborines was evaluated by computing nuclear
      independent chemical shift (NICS) values. Collectively, the experimental and
      computational studies indicate the unsaturated central BOC4 ring has appreciable
      aromatic character. 

PMID- 27040725
TI  - Association between serum soluble tumor necrosis factor-alpha receptors and early
      childhood obesity.
AB  - This study aimed to characterize the inflammatory cytokine profiles and further
      validate the significantly different cytokines in the serum obtained from obese
      children aged 36-48 months. Four obese children and four lean controls were
      randomly selected for inflammatory cytokine array assay, in which two cytokines
      [soluble tumor necrosis factor-alpha receptors (sTNFRs) 1 and 2] were found to be
      significantly different. Both cytokines (sTNFR1 and sTNFR2) were then further
      validated through enzyme-linked immunosorbent assay (ELISA) in 61 obese children
      and 52 lean children. ELISA results revealed that serum sTNFR1 level in obese
      children significantly increased (p = 0.003), whereas sTNFR2 did not change
      significantly (p = 0.069). Stratified analysis by gender showed that only obese
      girls presented increased sTNFR1 (p = 0.005) and sTNFR2 (p = 0.049) levels. We
      conclude that serum sTNFR1 is elevated in early childhood obesity. Moreover,
      serum sTNFR1 and sTNFR2 are associated with obese girls but not obese boys,
      thereby suggesting that serum sTNFRs in early childhood obesity may be sex
      related. 

PMID- 27040726
TI  - Exposure Matching for Extrapolation of Efficacy in Pediatric Drug Development.
AB  - During drug development, matching adult systemic exposures of drugs is a common
      approach for dose selection in pediatric patients when efficacy is partially or
      fully extrapolated. This is a systematic review of approaches used for matching
      adult systemic exposures as the basis for dose selection in pediatric trials
      submitted to the US Food and Drug Administration (FDA) between 1998 and 2012. The
      trial design of pediatric pharmacokinetic (PK) studies and the pediatric and
      adult systemic exposure data were obtained from FDA publicly available databases
      containing reviews of pediatric trials. Exposure-matching approaches that were
      used as the basis for pediatric dose selection were reviewed. The PK data from
      the adult and pediatric populations were used to quantify exposure agreement
      between the 2 patient populations. The main measures were the pediatric PK
      studies' trial design elements and drug systemic exposures (adult and pediatric).
      There were 31 products (86 trials) with full or partial extrapolation of efficacy
      with an available PK assessment. Pediatric exposures had a range of mean Cmax and
      AUC ratios (pediatric/adult) of 0.63 to 4.19 and 0.36 to 3.60, respectively.
      Seven of the 86 trials (8.1%) had a predefined acceptance boundary used to match
      adult exposures. The key PK parameter was consistently predefined for antiviral
      and anti-infective products. Approaches to match exposure in children and adults
      varied across products. A consistent approach for systemic exposure matching and
      evaluating pediatric PK studies is needed to guide future pediatric trials.

PMID- 27040727
TI  - Optical Magnetic Induction Tomography of the Heart.
AB  - Atrial Fibrillation (AF) affects a significant fraction of the ageing population,
      causing a high level of morbidity and mortality. Despite its significance, the
      causes of AF are still not uniquely identified. This, combined with the lack of
      precise diagnostic and guiding tools, makes the clinical treatment of AF sub
      optimal. We identify magnetic induction tomography as the most promising
      technique for the investigation of the causes of fibrillation and for its
      clinical practice. We therefore propose a novel optical instrument based on
      optical atomic magnetometers, fulfilling the requirements for diagnostic mapping
      of the heart's conductivity. The feasibility of the device is here discussed in
      view of the final application. Thanks to the potential of atomic magnetometers
      for miniaturisation and extreme sensitivity at room temperature, a new generation
      of compact and non-invasive diagnostic instrumentation, with both bedside and
      intra-operative operation capability, is envisioned. Possible scenarios both in
      clinical practice and biomedical research are then discussed. The flexibility of
      the system makes it promising also for application in other fields, such as
      neurology and oncology. 

PMID- 27040723
TI  - Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy.
AB  - BACKGROUND: The survival benefit of a strategy of coronary-artery bypass grafting
      (CABG) added to guideline-directed medical therapy, as compared with medical
      therapy alone, in patients with coronary artery disease, heart failure, and
      severe left ventricular systolic dysfunction remains unclear. METHODS: From July
      2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or
      less and coronary artery disease amenable to CABG were randomly assigned to
      undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy
      alone (medical-therapy group, 602 patients). The primary outcome was death from
      any cause. Major secondary outcomes included death from cardiovascular causes and
      death from any cause or hospitalization for cardiovascular causes. The median
      duration of follow-up, including the current extended-follow-up study, was 9.8
      years. RESULTS: A primary outcome event occurred in 359 patients (58.9%) in the
      CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio
      with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97;
      P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and
      297 patients (49.3%) in the medical-therapy group died from cardiovascular causes
      (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from
      any cause or hospitalization for cardiovascular causes occurred in 467 patients
      (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy
      group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test).
      CONCLUSIONS: In a cohort of patients with ischemic cardiomyopathy, the rates of
      death from any cause, death from cardiovascular causes, and death from any cause
      or hospitalization for cardiovascular causes were significantly lower over 10
      years among patients who underwent CABG in addition to receiving medical therapy
      than among those who received medical therapy alone. (Funded by the National
      Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number,
      NCT00023595.).

PMID- 27040728
TI  - A Mysterious Crescent in the Heart: Ruptured Sinus of Valsalva Dissecting
      Interatrial Septum, Multimodality Imaging, and Full Recovery.
AB  - A 59-year-old man who was admitted to the emergency department with new and
      spontaneous onset of fatigue, dyspnea, and palpitations. There was neither a
      history of trauma, chest pain, nor infection. Transthoracic two- and three
      dimensional echocardiography and computer tomography demonstrated sinus of
      Valsalva aneurysm rupture dissecting interatrial septum and leading to a huge
      thrombus formation in it. The diagnosis with multimodality imaging performed
      within hours, and urgent surgery saved the patient's life.

PMID- 27040730
TI  - Branchial nitrogen cycle symbionts can remove ammonia in fish gills.
AB  - Knowledge of the mechanisms by which fish excrete their metabolic nitrogenous
      waste and insights into nitrogen cycling in aquaculture systems is of utmost
      importance to improve the sustainable commercial production of fish. In fish,
      most nitrogenous waste is excreted via the gills as ammonia, a potentially toxic
      nitrogenous compound. In this study; activity assays, physiological experiments,
      molecular analysis and microscopy were used to show that the gills of fish harbor
      a unique combination of hitherto overlooked nitrogen-cycle microorganisms that
      can theoretically detoxify excreted ammonia by converting it into inert
      dinitrogen gas. By doing so, these microorganisms may benefit from the ammonia
      supply by the host and prevent the build-up of this compound to toxic
      concentrations. This novel relationship between vertebrates and microorganisms
      may shed new light on nitrogen handling by ammonotelic fish species.

PMID- 27040731
TI  - Survey of student attitudes towards digital simulation technologies at a dental
      school in China.
AB  - INTRODUCTION: Digital simulation technologies have become widespread in
      healthcare education, especially in dentistry; these technologies include digital
      X-ray images, digital microscopes, virtual pathology slides and other types of
      simulation. This study aimed to assess students' attitudes towards digital
      simulation technologies at a large, top-ranked dental school in China, as well as
      find out how students compare the digital technologies with traditional training
      methods. METHODS: In April 2015, a custom-designed questionnaire was distributed
      to a total of 389 students who had received digital technology and simulation
      based training in West China Dental School during 2012-2014. RESULTS: Results of
      a cross-sectional survey show that most students accept digital simulation
      technology; they report that the technology is stimulating and facilitates self
      directed and self-paced learning. CONCLUSION: These findings, together with the
      objective advantages of digital technology, suggest that digital simulation
      training offers significant potential for dental education, highlighting the need
      for further research and more widespread implementation.

PMID- 27040729
TI  - Traumatic Axonal Injury: Mechanisms and Translational Opportunities.
AB  - Traumatic axonal injury (TAI) is an important pathoanatomical subgroup of
      traumatic brain injury (TBI) and a major driver of mortality and functional
      impairment. Experimental models have provided insights into the effects of
      mechanical deformation on the neuronal cytoskeleton and the subsequent processes
      that drive axonal injury. There is also increasing recognition that axonal or
      white matter loss may progress for years post-injury and represent one
      mechanistic framework for progressive neurodegeneration after TBI. Previous
      trials of novel therapies have failed to make an impact on clinical outcome, in
      both TBI in general and TAI in particular. Recent advances in understanding the
      cellular and molecular mechanisms of injury have the potential to translate into
      novel therapeutic targets.

PMID- 27040732
TI  - Microstructure and Mechanical Property of Glutaraldehyde-Treated Porcine
      Pulmonary Ligament.
AB  - There is a significant need for fixed biological tissues with desired structural
      and material constituents for tissue engineering applications. Here, we introduce
      the lung ligament as a fixed biological material that may have clinical utility
      for tissue engineering. To characterize the lung tissue for potential clinical
      applications, we studied glutaraldehyde-treated porcine pulmonary ligament (n =
      11) with multiphoton microscopy (MPM) and conducted biaxial planar experiments to
      characterize the mechanical property of the tissue. The MPM imaging revealed that
      there are generally two families of collagen fibers distributed in two distinct
      layers: The first family largely aligns along the longitudinal direction with a
      mean angle of theta = 10.7 +/- 9.3 deg, while the second one exhibits a random
      distribution with a mean theta = 36.6 +/- 27.4. Elastin fibers appear in some
      intermediate sublayers with a random orientation distribution with a mean theta =
      39.6 +/- 23 deg. Based on the microstructural observation, a microstructure-based
      constitutive law was proposed to model the elastic property of the tissue. The
      material parameters were identified by fitting the model to the biaxial stress
      strain data of specimens, and good fitting quality was achieved. The parameter e0
      (which denotes the strain beyond which the collagen can withstand tension) of
      glutaraldehyde-treated tissues demonstrated low variability implying a relatively
      consistent collagen undulation in different samples, while the stiffness
      parameters for elastin and collagen fibers showed relatively greater variability.
      The fixed tissues presented a smaller e0 than that of fresh specimen, confirming
      that glutaraldehyde crosslinking increases the mechanical strength of collagen
      based biomaterials. The present study sheds light on the biomechanics of
      glutaraldehyde-treated porcine pulmonary ligament that may be a candidate for
      tissue engineering.

PMID- 27040733
TI  - A Gunpowder Tattoo in a 6-Year-Old Girl.
AB  - Gunpowder tattoos result from explosion and subsequent traumatic implantation of
      pigmented granules into varying layers of the skin. This report details the case
      of a 6-year-old with a gunpowder tattoo on the face. 

PMID- 27040734
TI  - Assessing sexual function and dysfunction in Turkish women undergoing surgical
      breast cancer treatment.
AB  - AIM: The purpose of this study was to determine whether there are differences
      between Turkish women undergoing postmastectomy breast reconstruction and those
      undergoing breast-conserving surgery (BCS) or mastectomy alone. METHODS: The
      sample of the study, which was designed as a descriptive and regressional one,
      consisted of a total of 100 female patients, 33 undergoing BCS, 34 undergoing
      postmastectomy breast reconstruction, and 33 undergoing mastectomy for breast
      cancer, between 2008 and 2012. Data were collected through an individual
      characteristics form and Female Sexual Function Index (FSFI). RESULTS: The
      comparison of the type of surgical procedure and the mean FSFI scores for the
      subscales of desire, arousal, orgasm, satisfaction, and pain, and the mean total
      FSFI scores revealed a statistically significant difference in favor of
      postmastectomy breast reconstruction and BCS (P < 0.05). When the authors
      evaluated the effects of age and surgical procedure type from the risk factors
      associated with total FSFI score classification by the logistic regression
      analysis, variations of age and surgical procedure type were found significant in
      the authors' model (P < 0.05). Age and surgical procedure type were independent
      risk factors effective on the total FSFI score of less than 26.55. CONCLUSION: In
      this study, based on the mean total FSFI scores of women, it was concluded that
      postmastectomy breast reconstruction had positive effects on sexual lives of
      Turkish women with breast cancer, that more satisfactory outcomes were obtained
      in those undergoing BCS, that mastectomy had negative effects on sexual function,
      thus leading to sexual dysfunction, and that age was negatively associated with
      sexual functions.

PMID- 27040735
TI  - Construction and evaluation of FiND, a fall risk prediction model of inpatients
      from nursing data.
AB  - AIM: To construct and evaluate an easy-to-use fall risk prediction model based on
      the daily condition of inpatients from secondary use electronic medical record
      system data. METHODS: The present authors scrutinized electronic medical record
      system data and created a dataset for analysis by including inpatient fall report
      data and Intensity of Nursing Care Needs data. The authors divided the analysis
      dataset into training data and testing data, then constructed the fall risk
      prediction model FiND from the training data, and tested the model using the
      testing data. RESULTS: The dataset for analysis contained 1,230,604 records from
      46,241 patients. The sensitivity of the model constructed from the training data
      was 71.3% and the specificity was 66.0%. The verification result from the testing
      dataset was almost equivalent to the theoretical value. CONCLUSION: Although the
      model's accuracy did not surpass that of models developed in previous research,
      the authors believe FiND will be useful in medical institutions all over Japan
      because it is composed of few variables (only age, sex, and the Intensity of
      Nursing Care Needs items), and the accuracy for unknown data was clear.

PMID- 27040736
TI  - Psychometric evaluation of the Diabetes Symptom Checklist-Revised in patients
      with type 2 diabetes in Turkey.
AB  - AIM: To evaluate the psychometric properties of the Diabetes Symptoms Checklist
      Revised (DSC-R), as measures of diabetes-related symptoms, in patients with type
      2 diabetes in Turkey. METHODS: This research was carried out on 340 patients
      diagnosed with type 2 diabetes in the Department of Endocrinology and Metabolic
      Diseases of a university hospital in Turkey, between 25 January 2011 and 1 April
      2011. Personal information forms developed by the researchers and the DSC-R were
      used as the data tools. All data were collected by authors during face-to-face
      interviews. RESULTS: According to the results of the research, the patients had a
      mean +/- standard deviation age 55.9 +/- 7.54 years (range, 20-65) and included
      most patients who were female (64.1%), married (87.1%), housewives (50.3%), and
      had completed primary education (47.4%). Cronbach's alpha found reliability for
      the total scale to be 0.92 and subscale alpha coefficients ranged 0.76-0.85.
      Confirmatory factor analysis resulted in a six factor structure: (i) neurology;
      (ii) psychology/fatigue; (iii) cardiology; (iv) ophthalmology; (v)
      psychology/cognition; and (vi) hyperglycemia. CONCLUSION: The Turkish version of
      the DSC-R was found to be a reliable and valid means to measure the level in
      effect on symptoms in patients with type 2 diabetes.

PMID- 27040737
TI  - Being as Normal as Possible: How Young People Ages 16-25 Years Evaluate the Risks
      and Benefits of Treatment for Inflammatory Arthritis.
AB  - OBJECTIVE: To explore how young people (ages 16-25 years) with inflammatory
      arthritis evaluate the risks and benefits of treatment, particularly treatment
      with biologic therapies. METHODS: This qualitative study involved in-depth
      interviews (n = 44) with young people, trusted others (e.g., parents), and health
      professionals; audio-recordings (n = 4) of biologic therapy-related
      consultations; and focus groups (n = 4). Analysis used techniques from grounded
      theory (open and focused coding, constant comparison, memoing, and mapping).
      RESULTS: Young people aspired to live what they perceived as a "normal" life.
      They saw treatment as presenting both an opportunity for and a threat to
      achieving this. Treatment changes were therefore subject to complex and ongoing
      evaluation, covering administration, associated restrictions, anticipated
      effects, and side effects. Information sources included expert opinion (of
      professionals and other patients) and personal experience. Previous treatments
      provided important reference points. Faced with uncertain outcomes, young people
      made provisional decisions. Both trusted others and health professionals
      expressed concern that young people were too focused on short-term outcomes.
      CONCLUSION: Young people value treatment that helps them to live a "normal" life.
      There is more to this than controlling disease. The emotional, social, and
      vocational consequences of treatment can be profound and lasting: opportunities
      to discuss the effects of treatment should be provided early and regularly. While
      making every effort to ensure understanding of the long-term clinical
      consequences of taking or not taking medication, the wider impact of treatment
      should not be dismissed. Only through understanding young people's values,
      preferences, and concerns can a sustainable balance between disease control and
      treatment burden be achieved.

PMID- 27040738
TI  - The mononuclear nickel(II) complex bis(azido-kappaN)bis[2,5-bis(pyridin-2-yl)
      1,3,4-thiadiazole-kappa2 N2 ,N3 ]nickel(II) protects tomato from Verticillium
      dahliae by inhibiting fungal growth and activating plant defences.
AB  - BACKGROUND: The antifungal properties of the nickel(II) complex bis(azido
      kappaN)bis[2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole-kappa2 N2 ,N3 ]nickel(II)
      [NiL2 (N3 )2 ] and its parental ligand 2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole
      were examined to evaluate their ability to protect tomato plants against
      Verticillium dahliae. Our main objectives were to determine their effects on the
      in vitro growth of the pathogen, and their aptitude for controlling verticillium
      wilt and activating plant defence responses in the greenhouse. RESULTS: NiL2 (N3
      )2 exhibited in vitro an elevated inhibition of radial growth of three strains of
      the pathogen. According to the strain, the EC50 values ranged from 10 to 29 ug mL
      1 for NiL2 (N3 )2 . In the greenhouse, it induced an elevated protection against
      V. dahliae when it was applied twice as foliar sprays at 50 ug mL-1 . It reduced
      the leaf alteration index by 85% and vessel browning by 96%. In addition, its
      protective ability was associated with the accumulation of H2 O2 and the
      activation of total phenolic content, as well as potentiation of the activity of
      peroxidase and polyphenol oxidase. CONCLUSION: These results demonstrated that
      the coordination of the ligand with Ni associated with the azide as a coligand
      resulted in an improvement in its biological activity by both inhibiting the
      growth of V. dahliae and activating plant defence responses. (c) 2016 Society of
      Chemical Industry.

PMID- 27040739
TI  - Structure and reorientational dynamics of 1-F-adamantane.
AB  - The polymorphism and the dynamics of a simple rigid molecule (1-fluoro
      adamantane) have been studied by means of X-ray powder diffraction and broadband
      dielectric spectroscopy. At temperatures below the melting point, the molecule
      forms an orientationally disordered Phase I with a cubic-centered structure
      (Phase I, Fm3-m, Z = 4). This phase possesses eight equilibrium positions for the
      fluorine atom, with equal occupancy factors of 1/8. A solid-solid phase
      transition to a low-temperature tetragonal phase (Phase II, P4-2(1)c, Z = 2)
      reduces the statistical disorder to only four possible equivalent sites for the
      fluorine atom, with fractional occupancies of 1/4. The dynamics has been
      rationalized under the constraints imposed by the space group of the crystal
      structure determined by powder X-ray diffraction. The dielectric spectroscopy
      study reveals that the statistical disorder in Phase II is dynamic in character
      and is associated with reorientational jumps along the two- and three-fold axes.
      In the dielectric loss spectra, the cooperative (alpha) relaxation exhibits a
      shoulder on the high-frequency side. This remarkable finding clearly reveals the
      existence of two intrinsic reorientational processes associated with the exchange
      of the F atom along the four sites. In addition to such "bimodal" relaxation, a
      secondary Johari-Goldstein relaxation is detected at lower temperatures.

PMID- 27040740
TI  - Cell cycle arrest induced by inhibitors of epigenetic modifications in maize (Zea
      mays) seedling leaves: characterization of the process and possible mechanisms
      involved.
AB  - Epigenetic modifications play crucial roles in the regulation of chromatin
      architecture and are involved in cell cycle progression, including mitosis and
      meiosis. To explore the relationship between epigenetic modifications and the
      cell cycle, we treated maize (Zea mays) seedlings with six different epigenetic
      modification-related inhibitors and identified the postsynthetic phase (G2 )
      arrest via flow cytometry analysis. Total H4K5ac levels were significantly
      increased and the distribution of H3S10ph signalling was obviously changed in
      mitosis under various treatments. Further statistics of the cells in different
      periods of mitosis confirmed that the cell cycle was arrested at preprophase.
      Concentrations of hydrogen peroxide were relatively higher in the treated plants
      and the antioxidant thiourea could negate the influence of the inhibitors.
      Moreover, all of the treated plants displayed negative results in the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling (TUNEL) and gamma-H2AX immunostaining assays after exposure for 3 d.
      Additionally, the expression level of topoisomerase genes in the treated plants
      was relatively lower than that in the untreated plants. These results suggest
      that these inhibitors of epigenetic modifications could cause preprophase arrest
      via reactive oxygen species formation inhibiting the expression of DNA
      topoisomerase genes, accompanied by changes in the H4K5ac and H3S10ph histone
      modifications.

PMID- 27040741
TI  - Evolution of urinary stone management in Australia and New Zealand.

PMID- 27040742
TI  - Appendicitis: 'to operate or not?' Should that be the question?

PMID- 27040743
TI  - Tranexamic acid in total joint arthroplasty.

PMID- 27040744
TI  - Medicine in small doses.

PMID- 27040746
TI  - Reply to: Reconstruction of the maxilla by submental flap.

PMID- 27040747
TI  - Re: Reconstruction of the maxilla by submental flap.

PMID- 27040748
TI  - Re: Transrectal ultrasound-guided biopsy sepsis and the rise in carbapenem
      antibiotic use.

PMID- 27040749
TI  - Response to Re: Transrectal ultrasound-guided biopsy sepsis and the rise in
      carbapenem antibiotic use.

PMID- 27040750
TI  - Response to Re: Randomized blinded control trial into tourniquet tolerance in
      awake volunteers.

PMID- 27040751
TI  - Re: Randomized blinded control trial into tourniquet tolerance in awake
      volunteers.

PMID- 27040752
TI  - Characterization of the low-temperature triplet state of chlorophyll in
      photosystem II core complexes: Application of phosphorescence measurements and
      Fourier transform infrared spectroscopy.
AB  - Phosphorescence measurements at 77 K and light-induced FTIR difference
      spectroscopy at 95 K were applied to study of the triplet state of chlorophyll a
      ((3)Chl) in photosystem II (PSII) core complexes isolated from spinach. Using
      both methods, (3)Chl was observed in the core preparations with doubly reduced
      primary quinone acceptor QA. The spectral parameters of Chl phosphorescence
      resemble those in the isolated PSII reaction centers (RCs). The main spectral
      maximum and the lifetime of the phosphorescence corresponded to 955+/-1 nm and of
      1.65+/-0.05 ms respectively; in the excitation spectrum, the absorption maxima of
      all core complex pigments (Chl, pheophytin a (Pheo), and beta-carotene) were
      observed. The differential signal at 1667(-)/1628(+)cm(-1) reflecting a downshift
      of the stretching frequency of the 13(1)-keto C=O group of Chl was found to
      dominate in the triplet-minus-singlet FTIR difference spectrum of core complexes.
      Based on FTIR results and literature data, it is proposed that (3)Chl is mostly
      localized on the accessory chlorophyll that is in triplet equilibrium with P680.
      Analysis of the data suggests that the Chl triplet state responsible for the
      phosphorescence and the FTIR difference spectrum is mainly generated due to
      charge recombination in the reaction center radical pair P680(+)PheoD1(-), and
      the energy and temporal parameters of this triplet state as well as the molecular
      environment and interactions of the triplet-bearing Chl molecule are similar in
      the PSII core complexes and isolated PSII RCs.

PMID- 27040753
TI  - Risk factors for recurrence in T1-2N0 gastric cancer in the United States and
      China.
AB  - INTRODUCTION: Recurrence patterns after curative intent gastrectomy for T1-2N0
      gastric adenocarcinoma are poorly defined. We sought to assess timing, patterns,
      and risk factors for recurrence in patients treated at two high-volume gastric
      cancer centers in the United States and China. METHODS: Between 1995 and 2011,
      1,058 patients underwent curative intent gastrectomy. Recurrences were classified
      as locoregional, distant, or peritoneal. Univariate and multivariate analyses
      were performed to identify risk factors for recurrence. RESULTS: Overall, 7% (76)
      of our 1,058 patients from the United States (n = 414) and China (n = 644)
      recurred. Liver (43%) was the most common site of recurrence in both countries
      (US: 24%, China: 52%), followed by peritoneum (16%), lymph nodes (10%), and
      anastomosis (8%). Median time to recurrence was 23 months (US: 30 months, China:
      23 months), which decreased with increasing T-stage (T1a: 27 months, T1b: 24
      months, T2: 22 months). Tumor size (P = 0.001), depth of invasion (P = 0.010),
      histological type (P = 0.022) and lymphovascular invasion (P = 0.001) were
      independently associated with recurrence. CONCLUSION: Patients infrequently recur
      following curative intent gastrectomy for T1-2N0 gastric adenocarcinoma. Almost
      all recurrences occur between six months and 3 years post-operatively, most
      frequently in distant anatomic locations; selective followup during this time
      period is recommended. J. Surg. Oncol. 2016;113:745-749. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27040754
TI  - Characterization of Ocular Iontophoretic Drug Transport of Ionic and Non-ionic
      Compounds in Isolated Rabbit Cornea and Conjunctiva.
AB  - Ocular iontophoresis (IP) in isolated rabbit cornea and conjunctiva was examined
      in terms of transport enhancement, tissue viability and integrity using
      electrophysiological parameters by the Ussing-type chamber technique. Lidocaine
      hydrochloride (LC, a cationic compound), sodium benzoate (BA, anionic compound),
      and fluorescein isothiocyanate labeled dextran (molecular weight 4400 Da, FD-4,
      hydrophilic large compound) were used as model permeants. Direct electric current
      was applied at 0.5-5.0 mA/cm(2) for the cornea and 0.5-20 mA/cm(2) for the
      conjunctiva for 30 min. LC and BA fluxes across the cornea and conjunctiva were
      significantly increased by the application of electric current up to 2.3- and 2.5
      fold and 4.0- and 3.4-fold, respectively, and returned to their baseline level on
      stopping the current. Furthermore, a much higher increase by IP application was
      obtained for the FD-4 transport. The increased FD-4 flux in the conjunctiva
      returned to baseline on stopping the current, whereas the flux in the cornea was
      sustained at a higher level after stopping the current. The transepithelial
      electric resistance of the cornea and conjunctiva was lowered by electric current
      application but fully recovered after stopping the current up to 2.0 mA/cm(2) for
      the cornea and 10 mA/cm(2) for the conjunctiva, suggesting that the corneal and
      conjunctival viability and integrity are maintained even after application of
      these current densities. These results indicate that ocular IP may be a useful
      non-invasive technique to achieve drug delivery of hydrophilic large molecules
      into the eyes. 

PMID- 27040755
TI  - Advanced light microscopy core facilities: Balancing service, science and career.
AB  - Core Facilities (CF) for advanced light microscopy (ALM) have become
      indispensable support units for research in the life sciences. Their
      organizational structure and technical characteristics are quite diverse,
      although the tasks they pursue and the services they offer are similar.
      Therefore, throughout Europe, scientists from ALM-CFs are forming networks to
      promote interactions and discuss best practice models. Here, we present
      recommendations for ALM-CF operations elaborated by the workgroups of the German
      network of ALM-CFs, German Bio-Imaging (GerBI). We address technical aspects of
      CF planning and instrument maintainance, give advice on the organization and
      management of an ALM-CF, propose a scheme for the training of CF users, and
      provide an overview of current resources for image processing and analysis.
      Further, we elaborate on the new challenges and opportunities for professional
      development and careers created by CFs. While some information specifically
      refers to the German academic system, most of the content of this article is of
      general interest for CFs in the life sciences. Microsc. Res. Tech. 79:463-479,
      2016. (c) 2016 THE AUTHORS MICROSCOPY RESEARCH AND TECHNIQUE PUBLISHED BY WILEY
      PERIODICALS, INC. 

PMID- 27040756
TI  - Fyn Kinase regulates GluN2B subunit-dominant NMDA receptors in human induced
      pluripotent stem cell-derived neurons.
AB  - NMDA receptor (NMDAR)-mediated fast excitatory neurotransmission is implicated in
      a broad range of physiological and pathological processes in the mammalian
      central nervous system. The function and regulation of NMDARs have been
      extensively studied in neurons from rodents and other non-human species, and in
      recombinant expression systems. Here, we investigated human NMDARs in situ by
      using neurons produced by directed differentiation of human induced pluripotent
      stem cells (iPSCs). The resultant cells showed electrophysiological
      characteristics demonstrating that they are bona fide neurons. In particular,
      human iPSC-derived neurons expressed functional ligand-gated ion channels,
      including NMDARs, AMPA receptors, GABAA receptors, as well as glycine receptors.
      Pharmacological and electrophysiological properties of NMDAR-mediated currents
      indicated that these were dominated by receptors containing GluN2B subunits. The
      NMDAR currents were suppressed by genistein, a broad-spectrum tyrosine kinase
      inhibitor. The NMDAR currents were also inhibited by a Fyn-interfering peptide,
      Fyn(39-57), but not a Src-interfering peptide, Src(40-58). Together, these
      findings are the first evidence that tyrosine phosphorylation regulates the
      function of NMDARs in human iPSC-derived neurons. Our findings provide a basis
      for utilizing human iPSC-derived neurons in screening for drugs targeting NMDARs
      in neurological disorders.

PMID- 27040758
TI  - Commentary: Targeted Inhibition of miR-155 Promotes Post-Stroke
      Neovascularization and Functional Recovery.

PMID- 27040759
TI  - Conference Report: 8th Clinical Trials on Alzheimer Disease (CTAD), Barcelona,
      Spain November 5-7, 2015.

PMID- 27040757
TI  - Splitsville: structural and functional insights into the dynamic bacterial Z
      ring.
AB  - Bacteria must divide to increase in number and colonize their niche. Binary
      fission is the most widespread means of bacterial cell division, but even this
      relatively simple mechanism has many variations on a theme. In most bacteria, the
      tubulin homologue FtsZ assembles into a ring structure, termed the Z ring, at the
      site of cytokinesis and recruits additional proteins to form a large protein
      machine - the divisome - that spans the membrane. In this Review, we discuss
      current insights into the regulation of the assembly of the Z ring and how the
      divisome drives membrane invagination and septal cell wall growth while flexibly
      responding to various cellular inputs. 

PMID- 27040760
TI  - Editorial: Linkage of CNS and Immunology with Psychology: Searching for New
      Pharmacological Targets.

PMID- 27040761
TI  - Dyschromatosis symmetrica hereditaria complicated by intracranial hemangiomas and
      Parry-Romberg syndrome.

PMID- 27040762
TI  - Extreme stiffness hyperbolic elastic metamaterial for total transmission
      subwavelength imaging.
AB  - Subwavelength imaging by metamaterials and extended work to pursue total
      transmission has been successfully demonstrated with electromagnetic and acoustic
      waves very recently. However, no elastic counterpart has been reported because
      earlier attempts suffer from considerable loss. Here, for the first time, we
      realize an elastic hyperbolic metamaterial lens and experimentally show total
      transmission subwavelength imaging with measured wave field inside the
      metamaterial lens. The main idea is to compensate for the decreased impedance in
      the perforated elastic metamaterial by utilizing extreme stiffness, which has not
      been independently actualized in a continuum elastic medium so far. The
      fabricated elastic lens is capable of directly transferring subwavelength
      information from the input to the output boundary. In the experiment, this
      intriguing phenomenon is confirmed by scanning the elastic structures inside the
      lens with laser scanning vibrometer. The proposed elastic metamaterial lens will
      bring forth significant guidelines for ultrasonic imaging techniques. 

PMID- 27040763
TI  - Focal adhesion kinase regulation in stem cell alignment and spreading on
      nanofibers.
AB  - While electrospun nanofibers have demonstrated the potential for novel tissue
      engineering scaffolds, very little is known about the molecular mechanism of how
      cells sense and adapt to nanofibers. Here, we revealed the role of focal adhesion
      kinase (FAK), one of the key molecular sensors in the focal adhesion complex, in
      regulating mesenchymal stem cell (MSC) shaping on nanofibers. We produced
      uniaxially aligned and randomly distributed nanofibers from poly(l-lactic acid)
      to have the same diameters (about 130 nm) and evaluated MSC behavior on these
      nanofibers comparing with that on flat PLLA control. C3H10T1/2 murine MSCs
      exhibited upregulations in FAK expression and phosphorylation (pY397) on
      nanofibrous cultures as assessed by immunoblotting, and this trend was even
      greater on aligned nanofibers. MSCs showed significantly elongated and well
      spread morphologies on aligned and random nanofibers, respectively. In the
      presence of FAK silencing via small hairpin RNA (shRNA), cell elongation length
      in the aligned nanofiber direction (cell major axis length) was significantly
      decreased, while cells still showed preferred orientation along the aligned
      nanofibers. On random nanofibers, MSCs with FAK-shRNA showed impaired cell
      spreading resulting in smaller cell area and higher circularity. Our study
      provides new data on how MSCs shape their morphologies on aligned and random
      nanofibrous cultures potentially via FAK-mediated mechanism.

PMID- 27040764
TI  - The regulation of autophagy in porcine blastocysts: Regulation of PARylation
      mediated autophagy via mammalian target of rapamycin complex 1 (mTORC1)
      signaling.
AB  - Poly(ADP-ribosyl)ation (PARylation) acts as a modulator of selective autophagic
      degradation of ubiquitinated aggregates for cellular quality control, functioning
      in pro-survival role. It was reported previously that the inhibition of
      PARylation resulted in autophagy defects leading accumulation of ubiquitinated
      aggregates SQSTM1/p62 and apoptosis in porcine blastocysts. Thus, this study aims
      to investigate the mechanism between PARylation and autophagy in porcine
      blastocysts. In vitro produced (IVP) embryos were treated with 3-aminobenzamide
      (3ABA, poly (ADP-ribose) polymerase inhibitor) and/or rapamycin (RAPA, an mTORC1
      inhibitor) during blastocyst formation. Then, these treated blastocysts were
      analyzed by real-time PCR, immunocytochemistry and TUNEL Assay. We found that the
      3ABA treatment increased mTORC1 downstream target, phosphorylation of thr389
      p70S6K (p-p70S6K-thr389), suggesting an increase in mTORC1 activity. Co-treatment
      with rapamycin (RAPA), mTORC1 inhibitor, restored the 3ABA-induced autophagy
      defects to those of the controls by normalizing mTORC1 activity. Moreover,
      autophagy induction, with only RAPA treatment, increased the rate of blastocyst
      development (70.05 +/- 0.93 vs. 50.61 +/- 3.49%), total cell number (58.48 +/-
      2.94 vs. 49.58 +/- 2.43) and blastomere survival, but decreased the accumulation
      of SQSTM1/p62 aggregates. In summary, mTORC1 signaling is a key mechanism of
      PARylation-autophagy and its inhibition improved developmental ability and embryo
      quality by promoting selective autophagic degradation of ubiquitinated aggregates
      in porcine blastocysts. Therefore, these findings have significant implications
      for understanding the importance of autophagy regulation for successful in vitro
      production of porcine embryos.

PMID- 27040765
TI  - Inter-domain interactions of TDP-43 as decoded by NMR.
AB  - TDP-43 inclusions have been found in ~97% ALS as well as an increasing spectrum
      of other neurodegenerative diseases including Alzheimer's. TDP-43 contains an
      ubiquitin-like fold, two RRMs and a prion-like domain, but whether they interact
      with each other remains unknown due to being intrinsically aggregation-prone.
      Nevertheless, this knowledge is pivotal to understanding physiological functions
      and pathological roles of TDP-43. Here as facilitated by our previous discovery
      which allowed NMR characterization of TDP-43 and its five dissected fragments, we
      successfully decoded that TDP-43 does have dynamic inter-domain interactions,
      which are coordinated by the intrinsically-disordered prion-like domain. Thus,
      TDP-43 appears to undergo conformational exchanges between "closed" and "open"
      states which are needed for its functions. Our study thus offers a mechanism by
      which cellular processes might control TDP-43 physiology and proteinopathy by
      mediating its inter-domain interactions. 

PMID- 27040766
TI  - Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell
      lymphoma.
AB  - Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic
      application in immunotherapy. One of the major strategies of the bsAb platform is
      the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A
      bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the
      other end with affinity for CD19, has been approved in the US and Europe for the
      treatment of acute lymphoblastic leukemia. However, due to their small size and
      lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short
      half-lives in vivo. Additionally, poor solubility, structural instability, and
      low production yields have also become major challenges in the bulk production
      process. To overcome these challenges, we have engineered a tetravalent bsAb with
      bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G
      (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker
      hinge domain (LHD) results in improved antibody stabilization and properties.
      Here we demonstrate this antibody's highly efficient cancer cell elimination in a
      dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro.
      Our data suggest the potential clinical application of this bsAb for the
      treatment of CD20-expressing B cell malignancies.

PMID- 27040767
TI  - Long noncoding RNA H19 regulates EZH2 expression by interacting with miR-630 and
      promotes cell invasion in nasopharyngeal carcinoma.
AB  - The long non-coding RNA (lncRNA) H19 has been recently shown to participate in
      the progression of cancer, including metastasis. However, the biological role of
      H19 and the underlying mechanisms mediating its functions in nasopharyngeal
      carcinoma (NPC) remain unclear. Herein, we found that H19 was overexpressed in
      NPC tissues and poorly differentiated cell lines. Knockdown of H19 significantly
      inhibited the invasive ability of NPC cells. Moreover, H19 affected the
      expression of enhancer of zeste homolog 2 (EZH2), which has also been observed to
      be up-regulated in NPC and to promote cell invasion. Rather than direct
      interaction, H19 regulated EZH2 expression by suppressing the activity of miR
      630, which is a repressor of EZH2 and interacts with H19 in a sequence-specific
      manner. Furthermore, H19 inhibited E-cadherin expression and promoted cell
      invasion of NPC cells via the miR-630/EZH2 pathway. Our data suggest an important
      role for H19 in NPC metastasis and suggest the feasibility of therapy for NPC
      involving modulation of the novel regulatory network.

PMID- 27040768
TI  - WITHDRAWN: miR-543 promotes proliferation and invasion of non-small cell lung
      cancer cells by inhibiting PTEN.

PMID- 27040769
TI  - Superior angiogenesis facilitates digit regrowth in MRL/MpJ mice compared to
      C57BL/6 mice.
AB  - Previous studies indicated that the fast-healer strain of MRL/MpJ-Fas(lpr)/J
      (MRL) mice demonstrated superior regenerative capabilities for digit wound
      healing and/or regeneration compared with the non-healer strain of C57BL/6 (C57)
      mice. These reports, however, mainly focused on morphological observations and
      analysis of gene expression with little attention on the role of angiogenesis in
      the amputated digits. By taking advantage of Laser Doppler Imaging and
      histological analysis, we examined the potential role(s) of angiogenesis in
      facilitating tissue regrowth/regeneration by comparing two strains of mice (MRL
      versus C57). The three middle digits on the mouse's right foot (RF) were
      amputated at the middle level of phalanx 2 (P2) on postnatal day 2 (Day 0), while
      the left foot (LF) remained intact and served as a control. Laser Doppler images
      and digital photographs were taken of both feet before, immediately after
      surgery, and on Day 7, 14, 21, and 28 to evaluate blood flow and overall length
      of digit regrowth. All measurements from the amputated digits of the RF were
      divided by those of the control LF to obtain normalized ratios for statistical
      comparisons between groups. It was found that MRL mice demonstrated an
      approximately 220% increase in regrowth ratios over that of C57 mice from Day 21
      28 (p < 0.01, n = 13), while blood-flow increased by about 25% on Day 21 (p <
      0.01, n = 13) compared to that in C57 mice. Histological analysis of both control
      and amputated limbs indicated an approximately 70% increase in the number of
      vessels (both arterial and venous) in MRL mice over that of the C57 mice (p <
      0.05, n = 3). We conclude that higher blood flow and angiogenesis may play an
      important role in facilitating the fast regrowth ratios of amputated digits in
      MRL mice compared to C57 mice.

PMID- 27040770
TI  - Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin
      sensitivity in mouse skeletal muscle.
AB  - A single bout of exercise is known to increase the insulin sensitivity of
      skeletal muscle; however, the underlying mechanism of this phenomenon is not
      fully understood. Because a single bout of exercise induces a transient increase
      in blood interleukin-6 (IL-6) level, we hypothesized that the enhancement of
      insulin sensitivity after a single bout of exercise in skeletal muscle is
      mediated at least in part through IL-6-dependent mechanisms. To test this
      hypothesis, C57BL6J mice were intravenously injected with normal IgG or an IL-6
      neutralizing antibody before exercise. Twenty-four hours after a single bout of
      exercise, the plantaris muscle was harvested to measure insulin sensitivity and
      glucose transporter (GLUT)-4 expression levels by ex-vivo insulin-stimulated 2
      deoxyglucose (2-DG) uptake and Western blotting, respectively. Compared with
      sedentary mice, mice that performed exercise showed enhanced IL-6 concentration,
      insulin-stimulated 2-DG uptake, and GLUT-4 expression in the plantaris muscle.
      The enhanced insulin sensitivity and GLUT4 expression were canceled by injection
      of the IL-6 neutralizing antibody before exercise. In addition, IL-6 injection
      increased GLUT4 expression, both in the plantaris muscle and the soleus muscle in
      C57BL6J mice. Furthermore, a short period of incubation with IL-6 increased GLUT4
      expression in differentiated C2C12 myotubes. In summary, these results suggested
      that IL-6 increased GLUT4 expression in muscle and that this phenomenon may play
      a role in the post-exercise enhancement of insulin sensitivity in skeletal
      muscle.

PMID- 27040771
TI  - Kappa opioid receptor activation alleviates experimental autoimmune
      encephalomyelitis and promotes oligodendrocyte-mediated remyelination.
AB  - Multiple sclerosis (MS) is characterized by autoimmune damage to the central
      nervous system. All the current drugs for MS target the immune system. Although
      effective in reducing new lesions, they have limited effects in preventing the
      progression of disability. Promoting oligodendrocyte-mediated remyelination and
      recovery of neurons are the new directions of MS therapy. The endogenous opioid
      system, consisting of MOR, DOR, KOR and their ligands, has been suggested to
      participate in the pathogenesis of MS. However, the exact receptor and mechanism
      remain elusive. Here we show that genetic deletion of KOR exacerbates
      experimental autoimmune encephalomyelitis, whereas activating KOR with agonists
      alleviates the symptoms. KOR does not affect immune cell differentiation and
      function. Instead, it promotes oligodendrocyte differentiation and myelination
      both in vitro and in vivo. Our study suggests that targeting KOR might be an
      intriguing way to develop new MS therapies that may complement the existing
      immunosuppressive approaches. 

PMID- 27040772
TI  - Association of microRNA-21 expression with clinicopathological characteristics
      and the risk of progression in advanced prostate cancer patients receiving
      androgen deprivation therapy.
AB  - BACKGROUND: Despite androgen deprivation therapy (ADT) remains the mainstay
      therapy for advanced prostate cancer (PCa), the patients have widely variable
      durations of response to ADT. Unfortunately, there is limited knowledge of pre
      treatment prognostic factors for response to ADT. Recently, microRNA-21 (miR-21)
      has been reported to play an important role in development of castration
      resistance of CaP. However, little is known about the expression of miR-21 in
      advanced PCa biopsy tissues, and data on its potential predictive value in
      advanced PCa are completely lacking. METHODS: In this study, paraffin-embedded
      prostate carcinoma tissues obtained by needle biopsy from 85 advanced PCa
      patients were evaluated for the expression levels of miR-21 by quantitative real
      time PCR (qRT-PCR). In situ hybridization (ISH) analysis was performed to further
      confirm the qRT-PCR results. Kaplan-Meier analysis and Cox proportional hazards
      regression models were performed to investigate the correlation between miR-21
      expression and time to progression of advanced PCa patients. RESULTS: Compared
      with adjacent non-cancerous prostate tissues, the expression level of miR-21 was
      significantly increased in PCa tissues (PCa vs. non-cancerous prostate: 1.3273 +/
      0.3207 vs. 0.9970 +/- 0.2054, P < 0.001). By and large, in ISH analysis miR-21
      was expressed at a higher level in tumor areas than in adjacent non-cancerous
      areas. Additionally, PCa patients with higher expression of miR-21 were
      significantly more likely to be of high Gleason score and high clinical stage (P
      < 0.05). There was no significant association between miR-21 expression and the
      initial prostate-specific antigen (PSA) level or age at diagnosis. Moreover,
      Kaplan-Meier survival analysis found that PCa patients with high miR-21
      expression have shorter progression-free survival than those with low miR-21
      expression. Furthermore, Multivariate Cox analysis revealed both miR-21
      expression status (P = 0.040) and clinical stage (P = 0.042) were all independent
      predictive factor for progression-free survival for advanced PCa. CONCLUSION:
      These findings suggest for the first time that the up-regulation of miR-21 may
      serve as an independent predictor of progress-free survival in patients with
      advanced PCa. Prostate 76:986-993, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27040773
TI  - Rab35 GTPase couples cell division with initiation of epithelial apico-basal
      polarity and lumen opening.
AB  - Establishment and maintenance of apico-basal polarity in epithelial organs must
      be tightly coupled with cell division, but the underlying molecular mechanisms
      are largely unknown. Using 3D cultures of renal MDCK cells (cysts), we found that
      the Rab35 GTPase plays a crucial role in polarity initiation and apical lumen
      positioning during the first cell division of cyst development. At the molecular
      level, Rab35 physically couples cytokinesis with the initiation of apico-basal
      polarity by tethering intracellular vesicles containing key apical determinants
      at the cleavage site. These vesicles transport aPKC, Cdc42, Crumbs3 and the lumen
      promoting factor Podocalyxin, and are tethered through a direct interaction
      between Rab35 and the cytoplasmic tail of Podocalyxin. Consequently, Rab35
      inactivation leads to complete inversion of apico-basal polarity in 3D cysts.
      This novel and unconventional mode of Rab-dependent vesicle targeting provides a
      simple mechanism for triggering both initiation of apico-basal polarity and lumen
      opening at the centre of cysts. 

PMID- 27040774
TI  - Illusory Visual Completion of an Object's Invisible Backside Can Make Your Finger
      Feel Shorter.
AB  - In a well-known magic trick known as multiplying balls, conjurers fool their
      audience with the use of a semi-spherical shell, which the audience perceives as
      a complete ball [1]. Here, we report that this illusion persists even when
      observers touch the inside of the shell with their own finger. Even more
      intriguingly, this also produces an illusion of bodily self-awareness in which
      the finger feels shorter, as if to make space for the purely illusory volume of
      the visually completed ball. This observation provides strong evidence for the
      controversial and counterintuitive idea that our experience of the hidden
      backsides of objects is shaped by genuine perceptual representations rather than
      mere cognitive guesswork or imagery [2].

PMID- 27040775
TI  - Reconstructing Carotenoid-Based and Structural Coloration in Fossil Skin.
AB  - Evidence of original coloration in fossils provides insights into the visual
      communication strategies used by ancient animals and the functional evolution of
      coloration over time [1-7]. Hitherto, all reconstructions of the colors of
      reptile integument and the plumage of fossil birds and feathered dinosaurs have
      been of melanin-based coloration [1-6]. Extant animals also use other mechanisms
      for producing color [8], but these have not been identified in fossils. Here we
      report the first examples of carotenoid-based coloration in the fossil record,
      and of structural coloration in fossil integument. The fossil skin, from a 10
      million-year-old colubrid snake from the Late Miocene Libros Lagerstatte (Teruel,
      Spain) [9, 10], preserves dermal pigment cells (chromatophores)-xanthophores,
      iridophores, and melanophores-in calcium phosphate. Comparison with chromatophore
      abundance and position in extant reptiles [11-15] indicates that the fossil snake
      was pale-colored in ventral regions; dorsal and lateral regions were green with
      brown-black and yellow-green transverse blotches. Such coloration most likely
      functioned in substrate matching and intraspecific signaling. Skin replicated in
      authigenic minerals is not uncommon in exceptionally preserved fossils [16, 17],
      and dermal pigment cells generate coloration in numerous reptile, amphibian, and
      fish taxa today [18]. Our discovery thus represents a new means by which to
      reconstruct the original coloration of exceptionally preserved fossil
      vertebrates.

PMID- 27040776
TI  - Enhanced Muscle Afferent Signals during Motor Learning in Humans.
AB  - Much has been revealed concerning human motor learning at the behavioral level
      [1, 2], but less is known about changes in the involved neural circuits and
      signals. By examining muscle spindle responses during a classic visuomotor
      adaptation task [3-6] performed by fully alert humans, I found substantial
      modulation of sensory afferent signals as a function of adaptation state.
      Specifically, spindle control was independent of concurrent muscle activity but
      was specific to movement direction (representing muscle lengthening versus
      shortening) and to different stages of learning. Increased spindle afferent
      responses to muscle stretch occurring early during learning reflected individual
      error size and were negatively related to subsequent antagonist activity (i.e.,
      60-80 ms thereafter). Relative increases in tonic afferent output early during
      learning were predictive of the subjects' adaptation rate. I also found that
      independent spindle control during sensory realignment (the "washout" stage)
      induced afferent signal "linearization" with respect to muscle length (i.e.,
      signals were more tuned to hand position). The results demonstrate for the first
      time that motor learning also involves independent and state-related modulation
      of sensory mechanoreceptor signals. The current findings suggest that adaptive
      motor performance also relies on the independent control of sensors, not just of
      muscles. I propose that the "gamma" motor system innervating spindles acts to
      facilitate the acquisition and extraction of task-relevant information at the
      early stages of sensorimotor adaptation. This designates a more active and
      targeted role for the human proprioceptive system during motor learning.

PMID- 27040777
TI  - Rapid Integration of Tactile and Visual Information by a Newly Sighted Child.
AB  - How we learn to interact with and understand our environment for the first time
      is an age-old philosophical question. Scientists have long sought to understand
      what is the origin of egocentric spatial localization and the perceptual
      integration of touch and visual information. It is difficult to study the
      beginnings of intermodal visual-motor and visual-tactile linkages in early
      infancy since infants' muscular strength and control cannot accurately guide
      visual-motor behavior and they do not concentrate well [1-6]. Alternatively, one
      can examine young children who have a restored congenital sensory modality loss.
      They are the best infant substitute if they are old enough for good muscle
      control and young enough to be within the classic critical period for
      neuroplasticity [7, 8]. Recovery studies after removal of dense congenital
      cataracts are examples of this, but most are performed on older subjects [9-14].
      We report here the results of video-recorded experiments on a congenitally blind
      child, beginning immediately after surgical restoration of vision. Her remarkably
      rapid development of accurate reaching and grasping showed that egocentric
      spatial localization requires neural circuitry needing less than a half hour of
      spatially informative experience to be calibrated. 32 hr after first sight, she
      visually recognized an object that she had simultaneously looked at and held,
      even though she could not use single senses alone (vision to vision; touch to
      touch) to perform this recognition until the following day. Then she also
      performed intersensory transfer of tactile object experience to visual object
      recognition, demonstrating that the two senses are prearranged to immediately
      become calibrated to one another.

PMID- 27040778
TI  - Cyanobacteria and Eukaryotic Algae Use Different Chemical Variants of Vitamin
      B12.
AB  - Eukaryotic microalgae and prokaryotic cyanobacteria are the major components of
      the phytoplankton. Determining factors that govern growth of these primary
      producers, and how they interact, is therefore essential to understanding aquatic
      ecosystem productivity. Over half of microalgal species representing marine and
      freshwater habitats require for growth the corrinoid cofactor B12, which is
      synthesized de novo only by certain prokaryotes, including the majority of
      cyanobacteria. There are several chemical variants of B12, which are not
      necessarily functionally interchangeable. Cobalamin, the form bioavailable to
      humans, has as its lower axial ligand 5,6-dimethylbenzimidazole (DMB). Here, we
      show that the abundant marine cyanobacterium Synechococcus synthesizes only
      pseudocobalamin, in which the lower axial ligand is adenine. Moreover,
      bioinformatic searches of over 100 sequenced cyanobacterial genomes for B12
      biosynthesis genes, including those involved in nucleotide loop assembly, suggest
      this is the form synthesized by cyanobacteria more broadly. We further
      demonstrate that pseudocobalamin is several orders of magnitude less bioavailable
      than cobalamin to several B12-dependent microalgae representing diverse lineages.
      This indicates that the two major phytoplankton groups use a different B12
      currency. However, in an intriguing twist, some microalgal species can use
      pseudocobalamin if DMB is provided, suggesting that they are able to remodel the
      cofactor, whereas Synechococcus cannot. This species-specific attribute
      implicates algal remodelers as novel and keystone players of the B12 cycle,
      transforming our perception of the dynamics and complexity of the flux of this
      nutrient in aquatic ecosystems.

PMID- 27040779
TI  - Independent Control of the Static and Dynamic Components of the Chlamydomonas
      Flagellar Beat.
AB  - When the green alga Chlamydomonas reinhardtii swims, it uses the breaststroke
      beat of its two flagella to pull itself forward [1]. The flagellar waveform can
      be decomposed into a static component, corresponding to an asymmetric time
      averaged shape, and a dynamic component, corresponding to the time-varying wave
      [2]. Extreme lightening conditions photoshock the cell, converting the
      breaststroke beat into a symmetric sperm-like beat, which causes a reversal of
      the direction of swimming [3]. Waveform conversion is achieved by a reduction in
      magnitude of the static component, whereas the dynamic component remains
      unchanged [2]. The coupling between static and dynamic components, however, is
      poorly understood, and it is not known whether the static component requires the
      dynamic component or whether it can exist independently. We used isolated and
      reactivated axonemes [4] to investigate the relation between the two beat
      components. We discovered that, when reactivated in the presence of low ATP
      concentrations, axonemes displayed the static beat component in absence of the
      dynamic component. Furthermore, we found that the amplitudes of the two
      components depend on ATP in qualitatively different ways. These results show that
      the decomposition into static and dynamic components is not just a mathematical
      concept but that the two components can independently control different aspects
      of cell motility: the static component controls swimming direction, whereas the
      dynamic component provides propulsion.

PMID- 27040780
TI  - An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice.
AB  - Odorant receptor (OR) gene choice in mammals is a paradigmatic example of
      monogenic and monoallelic transcriptional selection, in which each olfactory
      sensory neuron (OSN) chooses to express one OR allele from over 1,000 encoded in
      the genome [1-3]. This process, critical for generation of the circuit from nose
      to brain [4-6], is thought to occur in two steps: a slow initial phase that
      randomly activates a single OR allele, followed by a rapid feedback that halts
      subsequent expression [7-14]. Inherent in this model is a finite failure rate
      wherein multiple OR alleles may be activated prior to feedback suppression [15,
      16]. Confronted with more than one receptor, the neuron would need to activate a
      refinement mechanism to eliminate multigenic OR expression and resolve unique
      neuronal identity [16], critical to the generation of the circuit from nose to
      olfactory bulb. Here we used a genetic approach in mice to reveal a new facet of
      OR regulation that corrects adventitious activation of multiple OR alleles,
      restoring monogenic OR expression and unique neuronal identity. Using the
      tetM71tg model system, in which the M71 OR is expressed in >95% of mature OSNs
      and potently suppresses the expression of the endogenous OR repertoire [10], we
      provide clear evidence of a post-selection refinement (PSR) process that winnows
      down the number of ORs. We further demonstrate that PSR efficiency is linked to
      OR expression level, suggesting an underlying competitive process and shedding
      light on OR gene switching and the fundamental mechanism of singular OR choice.

PMID- 27040781
TI  - A Temporally Controlled Inhibitory Drive Coordinates Twitch Movements during REM
      Sleep.
AB  - During REM sleep, skeletal muscles are paralyzed in one moment but twitch and
      jerk in the next. REM sleep twitches are traditionally considered random motor
      events that result from momentary lapses in REM sleep paralysis [1-3]. However,
      recent evidence indicates that twitches are not byproducts of REM sleep, but are
      in fact self-generated events that could function to promote motor learning and
      development [4-6]. If REM twitches are indeed purposefully generated, then they
      should be controlled by a coordinated and definable mechanism. Here, we used
      behavioral, electrophysiological, pharmacological, and neuroanatomical methods to
      demonstrate that an inhibitory drive onto skeletal motoneurons produces a
      temporally coordinated pattern of muscle twitches during REM sleep. First, we
      show that muscle twitches in adult rats are not uniformly distributed during REM
      sleep, but instead follow a well-defined temporal trajectory. They are largely
      absent during REM initiation but increase steadily thereafter, peaking toward REM
      termination. Next, we identify the transmitter mechanism that controls the
      temporal nature of twitch activity. Specifically, we show that a GABA and glycine
      drive onto motoneurons prevents twitch activity during REM initiation, but
      progressive weakening of this drive functions to promote twitch activity during
      REM termination. These results demonstrate that REM twitches are not random
      byproducts of REM sleep, but are instead rather coherently generated events
      controlled by a temporally variable inhibitory drive.

PMID- 27040782
TI  - Long-Term Retention of CENP-A Nucleosomes in Mammalian Oocytes Underpins
      Transgenerational Inheritance of Centromere Identity.
AB  - Centromeres control genetic inheritance by directing chromosome segregation but
      are not genetically encoded themselves. Rather, centromeres are defined by
      nucleosomes containing CENP-A, a histone H3 variant [1]. In cycling somatic
      cells, centromere identity is maintained by an established cell-cycle-coupled
      CENP-A chromatin assembly pathway, but how centromeres are inherited through the
      mammalian female germline is unclear because of the long (months to decades)
      prophase I arrest. Here we show that mouse oocytes retain the pool of CENP-A
      nucleosomes assembled before birth, and that this pool is sufficient for
      centromere function, fertility, and genome transmission to embryos. Indeed,
      oocytes lack any measurable CENP-A nucleosome assembly through the entire fertile
      lifespan of the female (>1 year). Thus, the remarkable stability of CENP-A
      nucleosomes confers transgenerational centromere identity in mammals.

PMID- 27040783
TI  - Short communication: Factors affecting vitamin B12 concentration in milk of
      commercial dairy herds: An exploratory study.
AB  - Only bacteria can synthesize vitamin B12, and this requires adequate Co supply.
      The natural source of vitamin B12 in human diets comes from animal products,
      especially those from ruminants. This study aimed to describe variability
      regarding vitamin B12 concentration in milk among and within commercial dairy
      herds in early lactation. A secondary objective was to explore potential causes
      for this variability such as genetic variation and diet characteristics. In
      total, 399 dairy cows (135 primiparous and 264 multiparous; 386 Holstein and 13
      Jersey cows) in 15 commercial herds were involved. Milk samples were taken at
      27.4+/-4.1 and 55.4+/-4.1d in milk. Neither parity (primiparous vs. multiparous)
      nor sampling time affected milk concentrations of vitamin B12. Nevertheless,
      vitamin B12 concentration in milk was highly variable among and within dairy
      herds. The lowest vitamin B12 concentration in milk of cows was observed in the
      Jersey herd. Among herds, vitamin B12 concentration in milk ranged from 2,309 to
      3,878 pg/mL; one glass (250mL) of milk from those herds would provide between 23
      and 40% of the vitamin B12 recommended daily allowance. Among individual cows,
      however, this provision varied between 16 and 57% of the recommendation. In spite
      of the limited size of the studied population, the heritability value was 0.23,
      suggesting that genetic selection could modify milk vitamin B12 concentration. We
      observed a positive relationship between milk vitamin B12 concentration and
      dietary acid detergent fiber content and a negative relationship between milk
      concentration of vitamin B12 and dietary crude protein content. 

PMID- 27040784
TI  - Short communication: Improving accuracy of predicting breeding values in
      Brazilian Holstein population by adding data from Nordic and French Holstein
      populations.
AB  - The present study investigated the improvement of prediction reliabilities for 3
      production traits in Brazilian Holsteins that had no genotype information by
      adding information from Nordic and French Holstein bulls that had genotypes. The
      estimated across-country genetic correlations (ranging from 0.604 to 0.726)
      indicated that an important genotype by environment interaction exists between
      Brazilian and Nordic (or Nordic and French) populations. Prediction reliabilities
      for Brazilian genotyped bulls were greatly increased by including data of Nordic
      and French bulls, and a 2-trait single-step genomic BLUP performed much better
      than the corresponding pedigree-based BLUP. However, only a minor improvement in
      prediction reliabilities was observed in nongenotyped Brazilian cows. The results
      indicate that although there is a large genotype by environment interaction,
      inclusion of a foreign reference population can improve accuracy of genetic
      evaluation for the Brazilian Holstein population. However, a Brazilian reference
      population is necessary to obtain a more accurate genomic evaluation. 

PMID- 27040785
TI  - Physicochemical properties of skim milk powders prepared with the addition of
      mineral chelators.
AB  - The objective of this study was to determine the effect of mineral chelator
      addition during skim milk powder (SMP) manufacture on the solubility, turbidity,
      soluble protein, and heat stability (HS). Three chelators (sodium citrate
      dihydrate, sodium polyphosphate, and disodium EDTA) at 3 different concentrations
      (5, 15, and 25mM) were added to skim milk concentrate (30% total solids), and the
      pH was adjusted to 6.65 before spray drying to produce SMP. Spray-dried SMP
      samples were tested for solubility index (SI). Additionally, samples were
      reconstituted to contain 9% total solids, adjusted to pH 7.0, and tested for
      turbidity, protein content from supernatants of ultracentrifuged samples, and HS.
      Lower SI values were observed for samples treated with 5mM disodium EDTA and
      sodium polyphosphate than control samples or samples with 5mM sodium citrate
      dihydrate. Furthermore, lower SI values were observed with an increased level of
      chelating agents regardless of chelator type. A decreased turbidity value was
      found with increasing levels of mineral chelating salt treatment. Low turbidity
      with increasing levels of added chelators may be associated with the dissociation
      of caseins from micelles. Furthermore, higher protein content was observed in
      supernatants of ultracentrifuged samples treated with increased level of
      chelators as compared with the control sample. Higher HS was observed in samples
      treated with 5mM compared with samples treated with 25mM mineral chelator. The
      results suggest improved solubility and HS upon addition of mineral chelators to
      SMP during its manufacture. 

PMID- 27040786
TI  - Comparison of model predictions with measurements: A novel model-assessment
      method.
AB  - Frequently, scientific findings are aggregated using mathematical models. Because
      models are simplifications of the complex reality, it is necessary to assess
      whether they capture the relevant features of reality for a given application. An
      ideal assessment method should (1) account for the stochastic nature of
      observations and model predictions, (2) set a correct null hypothesis, (3) treat
      model predictions and observations interchangeably, and (4) provide
      quantitatively interpretable statistics relative to precision and accuracy.
      Current assessment methods show deficiencies in regards to at least one of these
      characteristics. The method being proposed is based on linear structural
      relationships. Unlike ordinary least-squares, where the projections from the
      observations to the regression line are parallel to the y-axis and inverse
      regression where they are parallel to the x-axis, the generalized projection
      regression method (GePReM) projects the observations on a regression line in a
      direction determined by the ratio of the precision of the observations to that of
      the mathematical model predictions. Estimation and testing issues arise when the
      model is expressed in the common slope-intercept format. A polar transformation
      circumvents these issues. The parameter for the angle between the regression line
      and the horizontal axis has symmetrical confidence intervals and is equivariant
      to the exchange of X and Y. The null hypothesis for the equivalence test is that
      the model predictions are not equivalent to the observations. Information size is
      calculated as the simple ratio of the variance of the true values of the
      observations and of the computer model predictions divided by their respective
      precision. This information size plays a critical role in determining the number
      of observations required and the size of the zone of practical tolerance for the
      equivalence tests. The terminology used in the comparison of measurement methods
      is adapted to that of model assessment based on the equivalence tests on the
      relative precision, regression slope, and mean bias. Two examples are presented,
      with complete details of the calculations required for parameter estimation,
      equivalence tests, and confidence intervals. The assessment method proposed is an
      alternative to other assessment methods available. Further research is required
      to establish the relative benefits and performance of this proposed method
      compared with others available in the literature. 

PMID- 27040787
TI  - Serum and colostral antibody production in cows immunized with recombinant human
      tumor necrosis factor.
AB  - The use of hyper-immune bovine colostrum as a human therapeutic platform is an
      emerging technology with potential to deliver the efficacy of antibody
      therapeutics with the convenience and safety of oral or topical application. It
      is necessary to understand how the bovine immune system responds to immunization
      with foreign proteins, both in terms of the serum antibody response and the
      transfer of antigen-specific antibodies into the colostrum to enable efficient
      large-scale production of therapeutic antibodies. We have immunized 25 cows with
      recombinant human tumor necrosis factor (rhTNF) and measured the levels of rhTNF
      specific antibodies in the serum and colostrum of these animals. We observed a
      decline of 84+/-9% in serum IgG1 concentrations in the final weeks of pregnancy
      that presumably reflects rapid transport of IgG1 into colostrum. The serum IgG2
      levels remained constant, such that the serum IgG1 to IgG2 ratio was 1:20 at
      parturition. We observed substantial animal-to-animal variability in the levels
      of anti-rhTNF antibodies in both serum and colostrum samples. In particular, a
      subset of 4 cows had extraordinarily high colostral anti-rhTNF antibody
      production. Only a weak correlation was found between the peak serum anti-rhTNF
      activity and the colostral anti-rhTNF activity in these animals. The 4 cows with
      high colostral anti-rhTNF activities trended toward higher serum IgG1 loss
      relative to average colostral anti-rhTNF producers, but this difference was not
      statistically significant in this small sample. The high-anti-rhTNF-producing
      cows also exhibited a greater proportion of rhTNF-specific antibodies that bound
      to bovine IgG1- and IgG2-specific detection antibodies relative to the total anti
      rhTNF immunoglobulin population. This finding suggests that the isotype
      distribution of the anti-rhTNF response is varied between individuals and genetic
      or environmental factors may increase the yield of antigen-specific colostral
      antibodies. 

PMID- 27040788
TI  - Control of Escherichia coli O157:H7 in contaminated alfalfa silage: Effects of
      silage additives.
AB  - This study was conducted to examine if adding microbial inoculants or propionic
      acid to alfalfa silages contaminated with Escherichia coli O157:H7 would inhibit
      the growth of the pathogen during or after ensiling. Alfalfa forage was harvested
      at the early bloom stage, wilted to a dry matter concentration of 54%, chopped to
      19-mm lengths, and ensiled after treatment with one of the following: (1)
      distilled water (control); (2) 1*10(5) cfu/g of E. coli O157:H7 (EC); (3) EC and
      1*10(6) cfu/g of Lactobacillus plantarum (EC+LP); (4) EC and 1*10(6) cfu/g of
      Lactobacillus buchneri (EC+LB); and (5) EC and 2.2g/kg of propionic acid (EC+PA).
      Each treatment was ensiled in quadruplicate in laboratory silos for 0, 3, 7, 16,
      and 100d and analyzed for EC counts, pH, and organic acids. In addition, samples
      from d 100 were analyzed for chemical composition, ammonia-N, counts of yeasts
      and molds, and aerobic stability. Escherichia coli O157:H7 was detected in all
      silages until d 7, but by d 16 it was not detected in those treated with EC+LB
      and EC+LP, though it was still detected in EC and EC+PA silages. However, by d
      100, the pathogen was not detected in any silage. The rate of pH decrease to 5.0
      was fastest for the EC+LP silage (7d), followed by the EC+LB silage (16d).
      Nevertheless, all silages had attained a pH of or less than 5.0 by d 100. The
      rapid decrease in pH in EC+LP and EC+LB silages was observed due to higher
      lactate and acetate concentrations, respectively, relative to the other silages
      during the early fermentation phase (d 3-16). Propionic acid was only detected in
      the EC+PA silage. Yeast counts were lowest in EC+LB and EC+PA silages. Subsamples
      of all d-100 silages were reinoculated with 1*10(5) cfu/g of EC immediately after
      silo opening. When the pathogen was subsequently enumerated after 168h of aerobic
      exposure, it was not detected in silages treated with EC+PA, EC+LB, or EC+LP,
      which all had pH values less than 5.0. Whereas the EC silage had a pH value of
      5.4 and 2.3 log cfu/g of the pathogen. Certain bacterial inoculants can hasten
      the inhibition of E. coli O157:H7 during ensiling, such as propionic acid, and
      they can also prevent its growth on silage contaminated with the pathogen after
      ensiling. 

PMID- 27040789
TI  - Evaluation of a lysostaphin-fusion protein as a dry-cow therapy for
      Staphylococcus aureus mastitis in dairy cattle.
AB  - This study evaluated the efficacy of a recombinant lysostaphin fused to a protein
      transduction domain (rLYS-PTD) as a dry-cow therapy for the treatment of
      experimentally induced chronic, subclinical Staphylococcus aureus mastitis.
      Twenty-two Holstein dairy cows were experimentally infected with Staph. aureus in
      a single pair of diagonal mammary quarters approximately 45d before dry off.
      Staphylococcus aureus-infected mammary quarters of cows were randomly assigned to
      1 of 2 treatment groups at dry off: (1) 279mg of rLYS-PTD in 50mL of vehicle
      (n=11 cows; 22 quarters) or (2) 50mL of vehicle solution (n=11 cows; 22 quarters)
      by intramammary infusion. All cows were followed for 30d postpartum to determine
      cure rates using bacteriologic culture, somatic cell counts, and clinical
      mastitis scores. No cures were recorded in either the treatment or control
      groups. Milk somatic cell count, bacterial colony counts, and mastitis scores did
      not significantly differ between treatment groups. In conclusion, rLYS-PTD was
      not an effective dry-cow therapeutic for chronic, subclinical Staph. aureus
      mastitis at the tested dose and formulation. 

PMID- 27040790
TI  - Use of early lactation milk recording data to predict the calving to conception
      interval in dairy herds.
AB  - Economic success in dairy herds is heavily reliant on obtaining pregnancies at an
      early stage of lactation. Our objective in this study was to attempt to predict
      the likelihood of conception occurring by d 100 and 150 of lactation (days in
      milk, DIM) by Markov chain Monte Carlo analysis using test day milk recording
      data and reproductive records gathered retrospectively from 8,750 cows from 33
      dairy herds located in the United Kingdom. Overall, 65% of cows recalved with 30,
      46, and 65% of cows conceiving by 100 DIM, 150 DIM, and beyond 150 DIM,
      respectively. Overall conception rate (total cows pregnant/total number of
      inseminations) was 27.47%. Median and mean calving to conception intervals were
      123 and 105 d, respectively. The probability of conception by both 100 DIM and
      150 DIM was positively associated with the average daily milk weight produced
      during the fourth week of lactation (W4MK) and protein percentage for test day
      samples collected between 0 to 30 and 31 to 60 DIM. Butterfat percentage at 0 to
      30 DIM was negatively associated with the probability of conception by 100 DIM
      but not at 150 DIM. High somatic cell count (SCC) at both 0 to 30 and 31 to 60
      DIM was negatively associated with the probability of conception by 100 DIM,
      whereas high SCC at 31 to 60 DIM was associated with a reduced probability of
      conception by 150 DIM. Increasing parity was associated with a reduced odds of
      pregnancy. Posterior predictions of the likelihood of conception for cows
      categorized as having "good" (W4MK >30kg and protein percentage at 0 to 30 and 31
      to 60 DIM >3.2%) or "poor" (W4MK <25kg and protein percentage at 0 to 30 and 31
      to 60 DIM <3.0%) early lactation attributes with actual observed values indicated
      model fit was good. The predicted likelihood of a "good" cow conceiving by 100
      and 150 DIM was 0.39 and 0.57, respectively (actual observed values 0.40 and
      0.59). The corresponding values for a "poor" cow were 0.28 and 0.42 (actual
      observed values 0.26 and 0.37). Predictions of the future reproductive success of
      cows may be possible using a limited number of early lactation attributes. 

PMID- 27040791
TI  - Circular RNA of cattle casein genes are highly expressed in bovine mammary gland.
AB  - Recent studies have revealed that, in addition to hormones and other protein
      factors, noncoding RNA molecules play an important regulatory role in milk
      protein synthesis. Circular RNAs (circRNAs) are universally expressed noncoding
      RNA species that have been proposed recently to regulate the expression of their
      parental genes. In the present study, the deep RNA-sequencing technique known as
      RNA-seq was used to compare expression profiles of circRNAs from 2 pooled RNA
      samples from cow mammary gland on d 90 and 250 postpartum and to identify the key
      circRNAs involved in lactation. A total of 4,804 and 4,048 circRNAs were
      identified in the cow mammary gland on d 90 and 250 postpartum, respectively, of
      which only 2,231 circRNAs were co-expressed at both lactation stages, suggesting
      high stage specificity in the circRNAs. The enrichment of some Gene Ontology
      terms for the circRNA parental genes differed between lactation stages. Among the
      top 10 enriched Gene Ontology terms, vesicle, endoplasmic reticulum, and
      mitochondrial lumen were more common on lactation d 90. All 4 casein-coding genes
      (CSN1S1, CSN1S2, CSN2, and CSN3) produced circRNAs in the cattle mammary gland.
      In total, 80 circRNAs were identified from these 4 genes; circRNAs from CSN1S1
      had very high abundance, and 3 of them accounted for 36% of all the circRNAs
      expressed in the mammary gland on lactation d 90. Three circRNAs from CSN1S1, 1
      circRNA from CSN1S2, and 1 circRNA from CSN2 were all more highly expressed on
      lactation d 90 than on lactation d 250, as confirmed by quantitative PCR. These
      circRNAs had several target sites for the microRNA miR-2284 family and were
      predicted to target CSN1S1 and CSN2 mRNA, suggesting their potential involvement
      in regulating expression of the casein genes. 

PMID- 27040792
TI  - Genotype by environment interaction for production, somatic cell score,
      workability, and conformation traits in Dutch Holstein-Friesian cows between
      farms with or without grazing.
AB  - In this study, genotype by environment interaction was investigated for
      production traits, somatic cell score (SCS), workability traits, and conformation
      traits for Holstein-Friesian cows producing on farms with or without grazing in
      the Netherlands. Additionally, heritabilities and repeatabilities were estimated
      in both farm systems. Data were available for 1,019 Dutch farms, and farm type
      was known for those farms, 142 farms without grazing and 877 farms with grazing.
      The data set consisted of 428,600 test-day records for production from 49,412
      cows, and from this data set a subset for SCS was created, consisting of 374,734
      test-day records from 45,955 cows. For workability and conformation traits, the
      data set consisted of 30,180 cows. Bivariate mixed models with multiple fixed
      effects and random sire and random permanent environment effects were applied.
      The majority of sires had daughters in both farm types. The heritabilities for
      milk yield (0.27), fat yield (0.19), and protein yield (0.20) were higher in
      farms with grazing than in farms without grazing with heritabilities of 0.24 for
      milk yield, 0.18 for fat yield, and 0.18 for protein yield. Repeatability was
      lower in the grazing farms for milk yield, fat yield, and protein yield, probably
      because of alternating quality of dry matter intake during grazing. Genetic
      correlations between grazing and no grazing were 0.99, 0.98, 0.97, and 1.00 for
      milk yield, fat yield, protein yield, and SCS, respectively. Genetic correlations
      for workability traits and conformation traits between grazing and no grazing
      varied between 0.93 and 1.00. For all traits, genetic correlations were close to
      unity, indicating no genotype by environment interaction between farms with or
      without grazing for production traits, SCS, workability traits, and conformation
      traits in Dutch Holstein-Friesians. Therefore, the same sires can be used for
      farms both with and without grazing. 

PMID- 27040793
TI  - Increasing the number of single nucleotide polymorphisms used in genomic
      evaluation of dairy cattle.
AB  - GeneSeek (Neogen Corp., Lexington, KY) designed a new version of the GeneSeek
      Genomic Profiler HD BeadChip for Dairy Cattle, which originally had >77,000
      single nucleotide polymorphisms (SNP). A set of >140,000 SNP was selected that
      included all SNP on the existing GeneSeek chip, all SNP used in US national
      genomic evaluations, SNP that were possible functional mutations, and other
      informative SNP. Because SNP with a lower minor allele frequency might track
      causative variants better, 30,000 more SNP were selected from the Illumina
      BovineHD Genotyping BeadChip (Illumina Inc., San Diego, CA) by choosing SNP to
      maximize differences in minor allele frequency between a SNP being considered for
      the new chip and the 2 SNP that flanked it. Single-gene tests were included if
      their location was known and bioinformatics indicated relevance for dairy cattle.
      To determine which SNP from the new chip should be included in genomic
      evaluations, genotypes available from chips already in use were used to impute
      and evaluate the SNP set. Effects for 134,511 usable SNP were estimated for all
      breed-trait combinations; SNP with the largest absolute values for effects were
      selected (5,000 for Holsteins, 1,000 for Jerseys, and 500 each for Brown Swiss
      and Ayrshires for each trait). To increase overlap with the 60,671 SNP currently
      used for genomic evaluation, 12,094 more SNP with the largest effects were added.
      After removing SNP with many parent-progeny conflicts, 84,937 SNP remained. Three
      cutoff studies were conducted with 3 SNP sets to determine reliability gain over
      that for parent average when evaluations based on August 2011 data were used to
      predict December 2014 performance. Across all traits, mean Holstein reliability
      gains were 32.5, 33.4, and 32.0 percentage points for 60,671, 84,937, and 134,511
      SNP, respectively. After genotypes from the new chip became available, the
      proposed set was reduced from 84,937 to 77,321 SNP to remove SNP that were not
      included during manufacture, reduce computing time, and improve imputation
      performance. The set of 77,321 SNP was evaluated using August 2011 data to
      predict April 2015 performance. Reliability gain over 60,671 SNP was 1.4
      percentage points across traits for Holsteins. Improvement over 84,937 SNP was
      partially the result of 4mo of additional data and genotypes from the new chip.
      Revision of the SNP set used for genomic evaluation is expected to be an ongoing
      process to increase evaluation accuracy. 

PMID- 27040794
TI  - Desogestrel enhances ventilation in ondine patients: Animal data involving
      serotoninergic systems.
AB  - Congenital central hypoventilation syndrome (CCHS) is a neurorespiratory disease
      characterized by life-threatening sleep-related hypoventilation involving an
      alteration of CO2/H(+) chemosensitivity. Incidental findings have suggested that
      desogestrel may allow recovery of the ventilatory response to CO2. The effects of
      desogestrel on resting ventilation have not been reported. This study was
      designed to test the hypothesis that desogestrel strengthens baseline ventilation
      by analyzing the ventilation of CCHS patients. Rodent models were used in order
      to determine the mechanisms involved. Ventilation in CCHS patients was measured
      with a pneumotachometer. In mice, ventilatory neural activity was recorded from
      ex vivo medullary-spinal cord preparations, ventilation was measured by
      plethysmography and c-fos expression was studied in medullary respiratory nuclei.
      Desogestrel increased baseline respiratory frequency of CCHS patients leading to
      a decrease in their PETCO2. In medullary spinal-cord preparations or in vivo
      mice, the metabolite of desogestrel, etonogestrel, induced an increase in
      respiratory frequency that necessitated the functioning of serotoninergic
      systems, and modulated GABAA and NMDA ventilatory regulations. c-FOS analysis
      showed the involvement of medullary respiratory groups of cell including
      serotoninergic neurons of the raphe pallidus and raphe obscurus nuclei that seem
      to play a key role. Thus, desogestrel may improve resting ventilation in CCHS
      patients by a stimulant effect on baseline respiratory frequency. Our data open
      up clinical perspectives based on the combination of this progestin with
      serotoninergic drugs to enhance ventilation in CCHS patients.

PMID- 27040795
TI  - Vilazodone does not inhibit sexual behavior in male rats in contrast to
      paroxetine: A role for 5-HT1A receptors?
AB  - Vilazodone (VLZ) is a selective serotonin reuptake inhibitor (SSRI) and 5-HT1A
      receptor partial agonist approved for the treatment of major depressive disorder
      in adults. In preclinical studies, VLZ had significantly lower sexual side
      effects than SSRIs and reduced serotonin transporter (SERT) levels in forebrain
      regions. In the current study, once-daily paroxetine (PAR, 10 mg/kg), VLZ (10
      mg/kg), PAR + buspirone (BUS, 3 mg/kg; a 5-HT1A partial agonist), or vehicle
      (VEH) was administered to male rats for 2 weeks then switched for 7 days (eg, PAR
      switched to VLZ, PAR + BUS, or VEH). Sexual behavior (eg, ejaculation frequency
      and latency) was evaluated 1-hr postdose on days 1, 7, 14, and 21. After 2 weeks,
      treatment with PAR but not VLZ resulted in a significant decrease in sexual
      behavior. In a 30-min test, the range of ejaculation frequency was 3.08-3.5 with
      VLZ and 1.00-1.92 with PAR (P < 0.05 vs VEH). After switching from PAR to VEH,
      PAR + BUS, or VEH, sexual behaviors were normalized to control levels. In
      contrast, the switch from VLZ to PAR resulted in reduced sexual behaviors. This
      preclinical study showed that unlike PAR, an SSRI with no 5-HT1A receptor
      activity, initial treatment with VLZ did not result in sexual side effects at
      therapeutically relevant doses. Results in male rats switched from PAR to VLZ or
      PAR + BUS strongly suggest that activation of 5-HT1A receptors may mitigate the
      sexual side effects associated with conventional SSRIs.

PMID- 27040796
TI  - Blood-brain barrier transport kinetics of the neuromedin peptides NMU, NMN, NMB
      and NT.
AB  - The neuromedin peptides are peripherally and centrally produced, but until now,
      it is generally believed that they only function as locally acting compounds
      without any quantitative knowledge about their blood-brain barrier (BBB) passage.
      Here, we characterize the transport kinetics of four neuromedins (NMU, NMN, NMB
      and NT) across the BBB, as well as their metabolization profile, and evaluate if
      they can act as endocrine hormones. Using the in vivo mouse model, multiple time
      regression (MTR), capillary depletion (CD) and brain efflux studies were
      performed. Data was fitted using linear (NMU, NT and NMB) or biphasic modeling
      (NMU and NMN). Three of the four investigated peptides, i.e. NMU, NT and NMN,
      showed a significant influx into the brain with unidirectional influx rate
      constants of 1.31 and 0.75 MUL/(g * min) for NMU and NT respectively and initial
      influx constants (K1) of 72.14 and 7.55 MUL/(g * min) and net influx constants
      (K) of 1.28 and 1.36 * 10(-16) MUL/(g*min) for NMU and NMN respectively. The
      influx of NMB was negligible. Only NMN and NT showed a significant efflux out of
      the brain with an efflux constant (kout) of 0.042 min(-1) and 0.053 min(-1)
      respectively. Our results indicate that locally produced neuromedin peptides
      and/or fragments can be transported through the whole body, including passing the
      BBB, and taken up by different organs/tissues, supporting the idea that the
      neuromedins could have a much bigger role in the regulation of biological
      processes than currently assumed.

PMID- 27040797
TI  - Physiology of Gas Exchange During ECMO for Respiratory Failure.
AB  - Management of gas exchange using extracorporeal membrane oxygenation (ECMO) in
      respiratory failure is very different than management when the patient is
      dependent on mechanical ventilation. All the gas exchange occurs in the membrane
      lung, and the arterial oxygenation is the result of mixing the ECMO blood with
      the native venous blood. To manage patients on ECMO, it is essential to
      understand the physiology described in this essay.

PMID- 27040798
TI  - Experimental manipulation of avoidable feelings of uncertainty: Effects on anger
      and anxiety.
AB  - Though anger and anxiety are related, putative explanations for this association
      remain unclear. Beliefs about one's state of uncertainty may be a pathway-the
      belief that one's uncertain state is unavoidable might lead to anxiety, whereas
      the belief that one's uncertain state is avoidable might lead to both anxiety and
      anger. To test this hypothesis, participants experienced an uncertainty induction
      and were then assigned to the avoidable uncertainty condition (experimental
      group) or the unavoidable uncertainty condition (control group). State anger and
      anxiety were assessed at baseline, following the uncertainty induction, and
      following the "avoidableness" manipulation. The uncertainty induction was
      successful; participants reported higher levels of anxiety at post-induction
      compared to baseline. As expected, the experimental group reported increases in
      anger from post-induction to post-manipulation whereas the control group reported
      decreases in anger. These findings suggest that when one's state of uncertainty
      is avoidable, anger is experienced alongside anxiety.

PMID- 27040799
TI  - Prolidase-proline dehydrogenase/proline oxidase-collagen biosynthesis axis as a
      potential interface of apoptosis/autophagy.
AB  - Prolidase is a cytosolic imidodipeptidase that specifically splits
      imidodipeptides with C-terminal proline or hydroxyproline. The enzyme plays an
      important role in the recycling of proline from imidodipeptides for resynthesis
      of collagen and other proline-containing proteins. The mechanism of prolidase
      dependent regulation of collagen biosynthesis was found at both transcriptional
      and post-transcriptional level. The increase in the enzyme activity is due to its
      phosphorylation on serine/threonine residues. Prolidase-dependent transcriptional
      regulation of collagen biosynthesis was found at the level of NF-kappaB, known
      inhibitor of type I collagen gene expression. Proline dehydrogenase/proline
      oxidase (PRODH/POX) is flavin-dependent enzyme associated with the inner
      mitochondrial membrane. The enzyme catalyzes conversion of proline into Delta(1) 
      pyrroline-5-carboxylate (P5C), during which reactive oxygen species (ROS) are
      produced, inducing intrinsic and extrinsic apoptotic pathways. Alternatively,
      under low glucose stress, PRODH/POX activation produces ATP for energy supply and
      survival. Of special interest is that PRODH/POX gene is induced by P53 and
      peroxisome proliferator-activated gamma receptor (PPARgamma). Among down
      regulators of PRODH/POX is an oncogenic transcription factor c-MYC and miR-23b*.
      On the other hand, PRODH/POX suppresses HIF-1alpha transcriptional activity, the
      MAPK pathway, cyclooxygenase-2, epidermal growth factor receptor and Wnt/b
      catenin signaling. PRODH/POX expression is often down-regulated in various
      tumors, limiting mitochondrial proline utilization to P5C. It is accompanied by
      increased cytoplasmic level of proline. Proline availability for PRODH/POX
      dependent ATP or ROS generation depends on activity of prolidase and utilization
      of proline in process of collagen biosynthesis. Therefore, Prolidase-PRODH/POX
      Collagen Biosynthesis axis may represent potential interface that regulate
      apoptosis and survival. (c) 2016 BioFactors, 42(4):341-348, 2016. 

PMID- 27040800
TI  - CT-guided percutaneous core-needle biopsy of pancreatic masses: comparison of the
      standard mesenteric/retroperitoneal versus the trans-organ approaches.
AB  - AIM: To compare the safety and efficacy of percutaneous computed tomography (CT)
      guided core-needle biopsy (CNB) of pancreatic masses traversing the
      gastrointestinal tract or solid viscera versus trans-mesenteric and
      retroperitoneal approaches. MATERIALS AND METHODS: CT-guided CNB of pancreatic
      lesions performed between May 2004 and December 2014 were retrospectively
      analysed at a single centre. Biopsies were performed using 18- or 20-G needles
      with a coaxial system. CT images, histopathology reports, medical records, and
      procedural details for all patients were reviewed to evaluate the biopsy route,
      complications, and diagnostic accuracy. According to the routes, biopsies were
      divided into trans-mesenteric, retroperitoneal and trans-organ approaches for
      comparison. RESULTS: A total of 85 patients, who had undergone 89 CNBs for
      pancreatic masses were reviewed. The overall sensitivity, specificity, and
      accuracy of CNB for detecting malignancy via various routes were 88.8%, 100%, and
      89.9%, respectively, with a complication rate of 20.2%. Trans-organ biopsies of
      pancreatic masses (n=22) were performed safely via a direct pathway traversing
      the stomach (n=14), colon (n=3), small bowel (n=2), liver (n=2), and spleen
      (n=1). The sensitivity, specificity, and accuracy were 90.5%, 100%, and 90.9%,
      respectively. In the trans-organ biopsy group, three biopsies (13.6%) resulted in
      minor haematomas, but no major complications occurred. There were no
      statistically significant differences in the diagnostic efficacy or complication
      rate among the different biopsy routes. CONCLUSION: Percutaneous CT-guided CNB
      using a trans-organ approach is a feasible technique for diagnosing pancreatic
      malignancy; however, as this series was small, more data is required.

PMID- 27040801
TI  - A randomised pilot study comparing 13 G vacuum-assisted biopsy and conventional
      14 G core needle biopsy of axillary lymph nodes in women with breast cancer.
AB  - AIM: To compare the acceptability, safety, and feasibility of vacuum-assisted
      biopsy (VAB) and core needle biopsy (CNB) of axillary lymph nodes in women with
      breast cancer. MATERIALS AND METHODS: This parallel, non-blinded, randomised
      study was approved by the National Research Ethics Service. Following written
      informed consent, women with abnormal appearing axillary lymph nodes and
      radiologically malignant breast masses were randomised 1:1 to lymph node sampling
      under local anaesthetic with either 14 G CNB or 13 G VAB in a single UK centre.
      Primary outcomes were study uptake rate and patient willingness to undergo a
      repeat procedure if necessary. Procedure duration, immediate and post-procedure
      pain scores, diagnostic yield, complications, and surgical histopathology were
      recorded. RESULTS: Ninety-five women were approached; 81 (85.3%) consented and
      were randomised. Forty underwent CNB; 40 underwent VAB; one was excluded. Median
      age was 57 years. The median procedure time was 2 minutes for both techniques.
      The median number of samples obtained was three for CNB and four for VAB. Median
      pain scores for the procedure and first 3 days were 1/10 and 1/10 for CNB and
      1/10 and 2/10 for VAB (p=0.11 and 0.04). More women were prepared to undergo
      repeat CNB compared to VAB, but the difference was not significant (38/39 versus
      33/39; p=0.11). Two patients developed a haematoma after VAB. One CNB and six
      VABs failed to yield adequate tissue (p=0.11), but the sensitivity was similar at
      79% and 78%. CONCLUSION: Study uptake was high. Acceptability of the two
      procedures was similar, but VAB was associated with more post-procedure pain. The
      sensitivity appears to be similar.

PMID- 27040802
TI  - Predicting the maturity of haemodialysis arteriovenous fistulas with colour
      Doppler ultrasound: a single-centre study from China.
AB  - AIM: To explore the optimal vascular diameter and blood flow measured by
      ultrasound to predict fistula maturity in Chinese patients. MATERIALS AND
      METHODS: One hundred and thirty-two patients were enrolled in the study. The
      blood flow and the diameters of the brachial artery, radial artery, and cephalic
      vein were analysed according to clinical outcomes. The performances of blood
      flow, cephalic vein diameter, and the two factors combined in predicting fistula
      maturity were evaluated and the optimal cut-off values for Chinese patients were
      determined. RESULTS: During a 6 month follow-up, 113 fistulas were classified as
      mature and 19 fistulas were classified as failure. In both groups, the diameters
      of the brachial and radial arteries increased gradually within 2 weeks post
      surgery (p<0.05), and cephalic vein diameter and blood flow increased within 4
      weeks post-surgery (p<0.05). The blood flow of the failure group was
      significantly lower than that of the mature group from the first day after
      creation. The area under the receiver operating characteristic (ROC) curve was
      0.95 (529 ml/min, the optimal cut-off value) for blood flow, 0.83 (5.2 mm) for
      cephalic vein diameter, and 0.96 for the two factors combined in predicting
      fistula maturity. CONCLUSIONS: For Chinese patients, blood flow >529 ml/min could
      be used to predict fistula maturity and cephalic vein diameter >5.2 mm could be a
      supplement when necessary.

PMID- 27040803
TI  - Resveratrol Treatment Inhibits Proliferation of and Induces Apoptosis in Human
      Colon Cancer Cells.
AB  - BACKGROUND: Resveratrol, a natural isolate from plant sources, has a long and
      important history in traditional Chinese medicine. In the present study we
      investigated the effect of resveratrol on human colon cancer cell lines.
      MATERIAL/METHODS: We used the Cell Counting kit-8 (CCK-8) for determination of
      colon cancer cell viability. Apoptosis induction was analyzed using the DeadEndTM
      Colorimetric TUNEL System (Promega, Madison, WI, USA). The siRNA Transfection
      Reagent kit (Santa Cruz Biotechnology, Inc.) was used for the administration of
      COX-2 silencer RNA (siRNA) into the colon cancer cells. Primer Express(r)
      software for Real-Time PCR ver. 3.0 (Applied Biosystems, Foster City, CA, USA)
      was used to prepare the primers for RT-PCR. RESULTS: The results revealed that
      exposure of colon cancer cells to resveratrol inhibited cell viability.
      Resveratrol exhibited a significant inhibitory effect on cell viability at 30 MUM
      concentration after 48 h of exposure. We observed that 30-MUM doses of
      resveratrol for 72 h led to 18, 29, and 34% reduction in the viability of HCA-17,
      SW480, and HT29 cells, respectively. It also significantly induced apoptosis in
      both of the tested carcinoma cell lines. The population of apoptotic cells in HCA
      17 and SW480 cell lines after 48 h of resveratrol treatment was 59.8+/-4 and
      67.2+/-4%, respectively, compared to 2.3+/-1% in the control cells. The colon
      cancer cells exposed to resveratrol showed significantly lower cyclooxygenase-2
      and prostaglandin receptor expression. Treatment of colon cancer cells with the
      inhibitor of cyclooxygenase-2, indomethacin, and administration of silencer RNA
      for cyclooxygenase-2 also produced similar results. CONCLUSIONS: These findings
      suggest that resveratrol treatment can be a promising strategy for the treatment
      of colon cancer.

PMID- 27040804
TI  - Leucocyte esterase, glucose and C-reactive protein in the diagnosis of prosthetic
      joint infections: a prospective study.
AB  - Analysis of joint fluid is of paramount importance for the diagnosis of
      prosthetic joint infections. Different markers of inflammation and/or infection
      in joint fluid have been proposed for diagnosis of these infections. In this
      study we evaluated the performance of leucocyte esterase, C-reactive protein
      (CRP) and glucose assays in synovial fluids from 129 patients with septic (n =
      27) or aseptic (n = 102) prosthetic joint failure. Samples were collected in
      serum tubes and centrifuged to limit the presence of corpuscle interfering with
      the assays. Determinations of leucocyte esterase and glucose were carried out by
      means of enzymatic colorimetric reactions performed on strips for urine analysis.
      Tests were considered positive when graded + or ++ whereas traces or absence of
      colour were considered negative. CRP was measured using an automated
      turbidimetric method and considered suggestive for infections when >10 mg/L.
      Leucocyte esterase was positive in 25/27 infected patients and negative in 99/102
      not infected patients (sensitivity 92.6%, specificity 97.0%). CRP was higher than
      the threshold in 22/27 infected patients and in 6/102 not infected patients
      (sensitivity: 81.5%; specificity: 94.1%) whereas glucose showed the lowest
      sensitivity (77.8%) and specificity (81.4%), being negative in 21/27 and 19/102
      infected and not infected patients, respectively. CRP led to a correct diagnosis
      in 19 of 22 patients with discordant esterase and glucose results. In conclusion,
      evaluation of leucocyte esterase, glucose and CRP may represent a useful tool for
      rapid diagnosis of prosthetic joint infections. 

PMID- 27040805
TI  - The L2b real-time PCR targeting the pmpH gene of Chlamydia trachomatis used for
      the diagnosis of lymphogranuloma venereum is not specific to L2b strains.
AB  - The French Reference Centre for chlamydiae uses two real-time PCRs targeting the
      pmpH gene of Chlamydia trachomatis to differentiate between L strains and variant
      L2b, responsible for a lymphogranuloma venereum outbreak in Europe. We compared
      the results obtained for 122 L2b C. trachomatis-positive specimens, using the two
      real-time PCRs, with the sequencing of the ompA gene. Only 91 specimens were
      confirmed as L2b. Our results demonstrate that the lymphogranuloma venereum
      outbreak is no longer dominated by the variant L2b, and that many L-positive
      specimens were misidentified as L2b with the method used, which raises the
      question of its specificity. 

PMID- 27040806
TI  - Post-mortem findings in a patient with avian influenza A (H5N6) virus infection.
AB  - Avian influenza A (H5N6) has been found to infect humans, and has resulted in ten
      cases with six deaths in China since 2014. Here, we describe the systematic post
      mortem pathology of a patient fatally infected with H5N6 virus and evaluate the
      associated pathogenesis compared with H1N1 pdm09 fatal cases. The most prominent
      histopathological features were diffuse alveolar damage and pulmonary vasculitis
      in the lungs of the patient. The virus disseminated to extrapulmonary organs,
      including the brain. Compared with H1N1 pdm09 fatal infection, H5N6 infection
      induced a more exacerbated immune response involving overt pulmonary
      inflammation, which led to alveolar damage and respiratory failure. 

PMID- 27040807
TI  - Risk factors associated with death or neurological deterioration among patients
      with Gram-negative postneurosurgical meningitis.
AB  - In a retrospective cohort of 115 patients with Gram-negative postneurosurgical
      meningitis, factors associated with 30-day mortality or neurological
      deterioration on multivariate analysis included days from admission to meningitis
      (OR 1.05 per day, 95% CI 1.02-1.09), decreased level of consciousness (OR 2.69,
      95% CI 0.99-7.31), blood glucose level >180 mg/dL (OR 3.70, 95% CI 1.27-10.77),
      higher creatinine level (OR 4.07 per 1 mg/dL, 95% CI 1.50-11.08), and
      cerebrospinal fluid glucose <50 mg/dL (OR 5.02, 95% CI 1.71-14.77) at diagnosis.
      A predictive score triaged patients into three groups with low (4/44, 9.1%),
      intermediate (16/38, 42.1%) and high (22/33, 66.7%) unfavourable outcome rates.
      Validation on a different group of 36 patients with Gram-negative
      postneurosurgical meningitis was acceptable. 

PMID- 27040808
TI  - The impact of "Ramadan fasting period" on total and differential white blood
      cells, haematological indices, inflammatory biomarker, respiratory symptoms and
      pulmonary function tests of healthy and asthmatic patients.
AB  - BACKGROUND: There is no conclusive evidence regarding the effect of fasting on
      different features in asthmatic patients. In the present study, the effect of
      Ramadan fasting in asthmatic patients and healthy control was studied. METHODS:
      Haematological indices, inflammatory mediators, pulmonary function tests (PFT)
      and respiratory symptoms were evaluated in 15 asthmatic patients compared to 14
      healthy matched control group before and after the one-month fasting period in
      Ramadan. The change in each parameter from the beginning to the end of Ramadan
      was calculated and referred to as "variation during Ramadan". RESULTS: The values
      of MCH, MCHC in both groups and monocyte counts in asthmatic patients, were
      significantly increased but platelet count was reduced in asthmatic and controls
      respectively compared to pre-Ramadan fasting period (P<0.05 to 0.001). Serum hs
      CRP level in control and asthmatic groups was significantly reduced after Ramadan
      fasting month (P<0.001 for both groups). PFT values after Ramadan fasting month
      in both groups were non-significantly higher compared to pre-fasting values
      except FVC. Respiratory symptoms in asthmatic patients were non-significantly but
      wheeze-o was significantly reduced after Ramadan fasting period in asthma group
      (P<0.05). There was no significant difference in variations of different
      parameters during Ramadan fasting period between two groups, although reduction
      of hs-CRP in asthmatic group was non-significantly higher than control group.
      CONCLUSION: These results show that Ramadan fasting period has no negative impact
      on asthma and may have some positive effect on asthma severity with regard to
      reduction of hs-CRP concentration and chest wheeze.

PMID- 27040809
TI  - Asymptomatic LTP sensitisation is common in plant-food allergic children from the
      Northeast of Spain.
AB  - BACKGROUND: The sensitisation profile at molecular level in plant-food allergy is
      complex. Several allergens may be involved, with different potential for severe
      reactions. lipid transfer proteins (LTP) are considered the most relevant plant
      food allergens in adults in Mediterranean countries, but less is known in
      children. AIM: To describe the clinical pattern and sensitisation profile of
      children with plant-food allergy and LTP sensitisation from Northeast Spain.
      METHODS: Children with history of immediate reaction to plant-food(s), positive
      skin-prick-test to the culprit plant-food(s) and specific-IgE to plant-food LTPs
      were analysed. RESULTS: 130 children were included. 69.2% (90/130) had reacted to
      >=2 taxonomically unrelated plant-foods. Peach, walnut, hazelnut and peanut were
      most frequently involved. Reactions severity ranged from anaphylaxis (45.4%,
      59/130) to oral symptoms only. Sensitisation to a particular plant-food LTP not
      always caused clinical symptoms with that plant-food; 69% (40/58) and 63% (17/27)
      of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3
      specific IgE, respectively. 65.4% (85/130) of children were also sensitised to
      storage proteins, which was associated to anaphylaxis and nut allergy. However,
      60% of patients without nuts/seeds allergy were sensitised to storage proteins.
      Specific-IgE levels to LTPs and/or storage proteins were not useful to predict
      allergy (vs. tolerance) to peach, walnut, peanut or hazelnut. CONCLUSIONS:
      Sensitisation to LTP and/or storage proteins without clear clinical significance
      is relatively common. Prospective longitudinal studies are required to evaluate
      the relevance of these silent sensitisations over time. Caution is required when
      interpreting the results of molecular-based diagnostic tools in clinical
      practice.

PMID- 27040810
TI  - Association of Interleukin-2, but not Interferon-Gamma, single nucleotide
      polymorphisms with juvenile idiopathic arthritis.
AB  - BACKGROUND: Cytokines, including interleukin-2 (IL-2) and interferon-gamma (IFN
      gamma), seem to play a role in the pathogenesis of juvenile idiopathic arthritis
      (JIA). The aim of this study was to investigate the associations of IL-2 and IFN
      gamma single nucleotide polymorphisms (SNPs) with susceptibility to JIA in an
      Iranian population. METHODS: Genomic DNA of 54 Iranian patients with JIA and 139
      healthy unrelated controls were typed for IL-2 (G/T at -330 and +166) as well as
      IFN-gamma gene (A/T at +874), using polymerase chain reaction with sequence
      specific primers method, and compared between patients and controls. RESULTS: A
      significantly higher frequency of the IL-2 -330 GG genotype (p<0.01) was found in
      the JIA patients compared to the controls. However, the GT genotype at the same
      position was notably lower than in controls (p<0.01). Moreover, IL-2 (-330, +166)
      GT haplotype was more frequent in patients with JIA in comparison with controls.
      No significant differences was observed between the two groups of case and
      control for IL-2 (G/T at +166) and IFN-gamma (A/T at +874) SNPs. CONCLUSION: The
      results of the current study suggest that certain SNPs of IL-2 gene have
      association with individuals' susceptibility to JIA. However, further
      investigations are required to confirm the results of this study.

PMID- 27040811
TI  - Enhancing the optical lever sensitivity of microcantilevers for dynamic atomic
      force microscopy via integrated low frequency paddles.
AB  - A method is presented to enhance the optical lever sensitivity in dynamic atomic
      force microscopy (AFM) by nearly an order of magnitude over a wide frequency
      bandwidth. This is achieved by fabricating or releasing a paddle with a soft
      hinge close to the free end of the AFM microcantilever such that the paddle
      resonance frequency is well below the fundamental resonance frequency of the
      microcantilever. We show a significant increase in signal to noise ratio when
      cantilever motion is observed at the paddle for AFM systems that are not limited
      by thermal noise. Also, any effects due to the excitation of the second eigenmode
      were decoupled by locating the paddle at the node of the second eigenmode. We use
      these probes for higher harmonic imaging in amplitude modulated AFM (AM-AFM) on a
      standard polymer blend made of polystyrene and low density polyethylene. We
      demonstrate significantly improved contrast in higher harmonic images when
      observing cantilever motion at the paddle. Thus this microcantilever design can
      improve significantly conventional cantilever performance for dynamic AFM and is
      compatible with low-cost, high yield microfabrication processes. 

PMID- 27040812
TI  - Naringin attenuates granule cell dispersion in the dentate gyrus in a mouse model
      of temporal lobe epilepsy.
AB  - Morphological abnormalities of the dentate gyrus (DG) are an important phenotype
      in the hippocampus of patients with temporal lobe epilepsy. We recently reported
      that naringin, a bioflavonoid in grapefruit and citrus fruits, exerts beneficial
      effects in the kainic acid (KA) mouse model of epilepsy. We found that naringin
      treatment reduced seizure activities and decreased autophagic stress and
      neuroinflammation in the hippocampus following in vivo lesion with KA. However,
      it remains unclear whether naringin may also attenuate seizure-induced
      morphological changes in the DG, collectively known as granule cell dispersion
      (GCD). To clarify whether naringin treatment reduces GCD, we evaluated the
      effects of intraperitoneal injection of naringin on GCD and activation of
      mammalian target of rapamycin complex 1 (mTORC1), an important regulator of GCD,
      following intrahippocampal injection of KA. Our results showed that naringin
      treatment significantly reduced KA-induced GCD and mTORC1 activation, which was
      confirmed by assessing the phosphorylated form of the mTORC1 substrate, 4E-BP1,
      in the hippocampus. These results suggest that naringin treatment may help
      prevent epilepsy-induced hippocampal injury by inhibiting mTORC1 activation and
      thereby reducing GCD in the hippocampus in vivo.

PMID- 27040813
TI  - Anti-atrial Fibrillatory Versus Proarrhythmic Potentials of Amiodarone: A New
      Protocol for Safety Evaluation In Vivo.
AB  - Anti-atrial fibrillatory and proarrhythmic potentials of amiodarone were
      simultaneously analyzed by using the halothane-anesthetized beagle dogs (n = 4)
      in order to begin to prepare standard protocol for clarifying both efficacy and
      adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of
      0.3 mg/kg of amiodarone hydrochloride decreased the heart rate and mean blood
      pressure. Additional administration of 3 mg/kg of amiodarone hydrochloride
      prolonged the QT interval besides the effects observed by the low dose, whereas
      it showed 1.6 times larger prolongation in the effective refractory period of the
      atrium than that of the ventricle, which may explain its clinical efficacy
      against atrial arrhythmias. However, no significant change was detected by either
      dose in the early repolarization assessed by corrected J-T peak or the late
      repolarization done by T peak-T end in the electrocardiogram, although the former
      tended to be shortened and the reverse was true for the latter. Lack of
      prolongation in the early repolarization will make it feasible to better
      understand why amiodarone lacks proarrhythmic potential in spite of the QT
      interval prolongation. Thus, these results of amiodarone obtained by current
      protocol may become a guidance on assessing efficacy and adverse effects of new
      anti-atrial fibrillatory drugs in vivo.

PMID- 27040814
TI  - Pharmacokinetic and pharmacodynamic study of a phospholipid-based phase
      separation gel for once a month administration of octreotide.
AB  - As a natural somatostatin analog, octreotide acetate (OCT) has been extensively
      used in cancer treatment and growth hormone related diseases. The clinical
      application of OCT, however, is greatly limited by its short half-life, rapid
      elimination and clearance in vivo. In the current study, a high content
      phospholipid-based phase separation gel platform (PPSG) was presented, which
      could be injected in the soluble state and underwent rapid phase-separation into
      a gel-like implant after a single subcutaneous injection. OCT was dispersed
      homogeneously in the PPSG pre-gel solution to afford OCT-loaded PPSG (OCT-PPSG)
      after a single subcutaneous injection, which displayed controlled and sustained
      release profiles for up to 30days in rats, rabbits and Beagle dogs. OCT-PPSG
      showed a less significant burst phase followed by a steady plasma concentration
      of OCT compared with Sandostatin((r)) (LAR) in Beagle dogs. Moreover, OCT-PPSG
      was demonstrated to show remarkable antitumor efficacy in both a primary rat
      model and a xenograft mouse model of hepatocellular carcinoma (HCC). PPSG thus
      represented a promising and viable in situ forming gel platform material for the
      long-term sustained release of peptides and protein drugs.

PMID- 27040815
TI  - A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy
      drug conjugate for targeted cancer therapy.
AB  - Targeted drug delivery is a broadly applicable approach for cancer therapy.
      However, the nanocarrier-based targeted delivery system suffers from batch-to
      batch variation, quality concerns and carrier-related toxicity issues. Thus, to
      develop a carrier-free targeted delivery system with nanoscale characteristics is
      very attractive. Here, a novel targeting small molecule nanodrug self-delivery
      system consisting of targeting ligand and chemotherapy drug was constructed,
      which combined the advantages of small molecules and nano-assemblies together and
      showed excellent targeting ability and long blood circulation time with well
      defined structure, high drug loading ratio and on-demand drug release behavior.
      As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the
      targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated
      through a pH-responsive hydrazone group. For its intrinsic amphiphilic property,
      Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro
      and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced
      anticancer activity and weak side effects. This novel active targeting nanodrug
      delivery system shows great potential in cancer therapy.

PMID- 27040816
TI  - Eradication of CD44-variant positive population in head and neck tumors through
      controlled intracellular navigation of cisplatin-loaded nanomedicines.
AB  - Eventual relapse of tumor growth is commonly observed in head and neck cancer
      patients, following treatment with platinum-based chemotherapies. This occurrence
      is believed to be related to the failure to eradicate drug resistant, cancer stem
      cell (CSC) niches, thereby enriching their population in tumors after treatment.
      In this study, we show that in contrast to free cisplatin (CDDP), the polymer
      micelle-based nanomedicine incorporating cisplatin (CDDP/m), can eradicate both
      the undifferentiated cell and the differentiated cancer cell populations within a
      head and neck tumor model. Immunohistochemistry of treated tumors showed that
      opposing to CDDP treatment, CDDP/m could reduce tumor growth without
      concentrating the CSC-like population. We further showed that CDDP/m, but not
      CDDP, can localize into hypoxic regions, possibly CSC-rich areas, in the tumors,
      and can overcome their detoxification mechanism based-on high cellular expression
      of glutathione to successfully deliver Pt to nuclear DNA. Our data suggests
      CDDP/m to be a replacement for current platinum therapies, for its ability to
      eradicate both bulk and CSC-like populations, and in turn to prevent recurrence
      of tumor growth.

PMID- 27040817
TI  - Quantitative non-contrast measurements improve diagnosing dural venous sinus
      thrombosis.
AB  - INTRODUCTION: The only direct sign of sinus thrombosis on non-contrast
      computerized tomography (NCCT) is the hyperdense sign. The purpose of our study
      was to assess quantitative parameters for diagnosis of superficial venous sinus
      thrombosis and to compare these quantitative criteria with the current standard
      of qualitative evaluation. METHODS: This retrospective case-control study
      included 18 patients with acute superficial sinus thrombosis and 18 matched
      controls. Three blinded readers independently evaluated the NCCT for the presence
      of hyperdense sign using axial slices only followed by axial slices with
      multiplanar reformats. Absolute attenuation values and ratios were calculated for
      thrombosed and non-thrombosed sinuses: Ratiotarget sinus/lowest attenuation
      sinus, Ratiotarget sinus/basilar artery, Ratiotarget sinus/internal carotid
      artery, Ratiotarget sinus/temporal lobe, and Ratiotarget sinus/frontal lobe.
      RESULTS: There was a significant difference in absolute attenuation values and
      ratios between thrombosed and non-thrombosed sinuses, with the absolute
      attenuation and the Ratiotarget sinus/lowest attenuation sinus being the most
      differentiating. The mean attenuation for thrombosed sinuses was 69 Hounsfield
      units (HU) (95 % CI 65-72 HU) vs. 52 HU (95 % CI 51-54) for non-thrombosed, P <
      0.0001. The mean Ratiotarget/lowest attenuation was 1.5 (95 % CI 1.4-1.6) for
      thrombosed sinuses vs. 1.1 (95 % CI 1.0-1.1) for non-thrombosed, P < 0.0001.
      Optimal thresholds of 62 HU and 1.3 yielded sensitivities of 81 and 84 %,
      respectively. Hyperdense sign had a sensitivity of 63 % on axial images and 67 %
      with the addition of multiplanar reformats. CONCLUSION: Density measurements
      result in substantial improvement over visual inspection in the diagnosis of
      superficial venous sinus thrombosis on NCCT.

PMID- 27040818
TI  - An in vitro study of alkaline phosphatase sensitivity to mixture of aflatoxin B1
      and fumonisin B1 in the hepatopancreas of coastal lagoon wild and farmed shrimp
      Litopenaeus vannamei.
AB  - This study aimed to establish the combined effect of aflatoxin B1 (AFB1) and
      fumonisin B1 (FB1) on wild Litopenaeus vannamei hepatopancreas alkaline
      phosphatase (AP) activity compared with that of farmed shrimp. AP activity in
      hepatopancreas extract was confirmed by several specific inhibitor assays. AP
      activity of wild shrimp was higher than that of farmed shrimp (p < 0.05).
      However, AP activity from both wild and farmed shrimp was inhibited when
      incubated with AFB1 and FB1. The greatest inhibition occurred when AP was
      incubated with a mixture of AFB1 and FB1. The IC50 for AFB1 on AP activity of
      wild and farmed shrimp hepatopancreases was 0.790 and 0.398 MUg/mL, respectively.
      The IC50 of FB1 was 0.87 MUg/mL for wild shrimp and 0.69 MUg/mL for farmed
      shrimp. These results suggest that, at the mycotoxins concentrations used in the
      study, AP from farmed L. vannamei was sensitive to the presence of both
      mycotoxins; however, AP is more sensitive to the combination of AFB1 + FB1
      suggesting a possible synergistic or potentiating inhibitory effect. 

PMID- 27040819
TI  - Occurrence of ochratoxin A in spices commercialized in Abidjan (Cote d'Ivoire).
AB  - Ochratoxin A (OTA) is a mycotoxin produced mostly by several species of
      Aspergillus and Penicillium. OTA is nephrotoxic in all animal species in which it
      has been tested and is cancerogenic in rodents. It is associated with Balkan
      endemic nephropathy. It is naturally present in many crop products such as
      cereals (barley, wheat, maize) and dried fruits, spices, coffee, wine, olives,
      and cocoa. The aim of this study was to assess the contamination of three
      Ivoirian spices with OTA (ginger, chili, and pepper) widely consumed by the
      population. A total of 90 spice samples (ginger: n = 30; chili: n = 30; pepper n
      = 30) was taken from various sales outlets of Abidjan. OTA was quantified using
      an HPLC apparatus coupled with a fluorimetric detector. The chili and ginger
      samples were contaminated with OTA at a mean concentration of 57.48 +/- 174 and
      0.12 +/- 0.15 MUg/kg, respectively. No contamination of the pepper samples was
      detected. Eight (26.67 %) of the chili samples exceeded the maximum limit of 15
      MUg/kg established by European regulation. These results should serve as an alert
      on the risk to the consumer population of these products that are highly
      contaminated with OTA. 

PMID- 27040820
TI  - Earthworm ecology affects the population structure of their Verminephrobacter
      symbionts.
AB  - Earthworms carry species-specific Verminephrobacter symbionts in their nephridia
      (excretory organs). The symbionts are vertically transmitted via the cocoon, can
      only colonize the host during early embryonic development, and have co-speciated
      with their host for about 100 million years. Although several studies have
      addressed Verminephrobacter diversity between worm species, the intra-species
      diversity of the symbiont population has never been investigated. In this study,
      symbiont population structure was examined by using a multi-locus sequence typing
      (MLST) approach on Verminephrobacter isolated from two contrasting ecological
      types of earthworm hosts: the high population density, fast reproducing compost
      worms, Eisenia andrei and Eisenia fetida, and the low-density, slow reproducing
      Aporrectodea tuberculata, commonly found in garden soils. Three distinct
      populations were investigated for both types and, according to MLST analysis of
      193 Verminephrobacter isolates, the symbiont community in each worm individual
      was very homogeneous. The more solitary A. tuberculata carried unique symbiont
      populations in 9 out of 10 host individuals, whereas the symbiont populations in
      the social compost worms were homogeneous across host individuals from the same
      population. These data suggested that host ecology shaped the population
      structure of Verminephrobacter symbionts. The homogeneous symbiont populations in
      the compost worms led to the hypothesis that Verminephrobacter could be
      transferred bi-parentally or via leaky horizontal transmission in high-density,
      frequently mating worm populations. 

PMID- 27040821
TI  - Decreased cysteine uptake by EAAC1 gene deletion exacerbates neuronal oxidative
      stress and neuronal death after traumatic brain injury.
AB  - Excitatory amino acid carrier type 1 (EAAC1), a high-affinity glutamate
      transporter, can expend energy to move glutamate into neurons. However, under
      normal physiological conditions, EAAC1 does not have a great effect on glutamate
      clearance but rather participates in the neuronal uptake of cysteine. This
      process is critical to maintaining neuronal antioxidant function by providing
      cysteine for glutathione synthesis. Previous study showed that mice lacking EAAC1
      show increased neuronal oxidative stress following transient cerebral ischemia.
      In the present study, we sought to characterize the role of EAAC1 in neuronal
      resistance after traumatic brain injury (TBI). Young adult C57BL/6 wild-type or
      EAAC1 (-/-) mice were subjected to a controlled cortical impact model for TBI.
      Neuronal death after TBI showed more than double the number of degenerating
      neurons in the hippocampus in EAAC1 (-/-) mice compared with wild-type mice.
      Superoxide production, zinc translocation and microglia activation similarly
      showed a marked increase in the EAAC1 (-/-) mice. Pretreatment with N-acetyl
      cysteine (NAC) reduced TBI-induced neuronal death, superoxide production and zinc
      translocation. These findings indicate that cysteine uptake by EAAC1 is important
      for neuronal antioxidant function and survival following TBI. This study also
      suggests that administration of NAC has therapeutic potential in preventing TBI
      induced neuronal death.

PMID- 27040822
TI  - Expression of a Chimeric Allergen with High Rare Codons Content in Codon Bias
      Adjusted Escherichia coli: Escherichia coli BL21 (DE3)-Codon Plus RIL as an
      Efficient Host.
AB  - The expression of heterologous proteins in Escherichia coli (E. coli) is
      importantly affected by codon bias. Hence, the aim of the current study was to
      determine which codon bias-adjusted E. coli strain is sufficient for expression
      of a chimeric allergen coded by high rare codon content. To investigate the
      expression level, a chimeric protein of Chenopodium album (C. album) was used as
      an appropriate model. An expression construct was assembled and was transformed
      to four strains of codon bias-adjusted E. coli including origami, BL21 (DE3),
      BL21 (DE3)-codon plus RIL, and Rosetta. The level of expression and solubility of
      the chimeric allergen was analyzed by SDS-PAGE. In addition, the allergenicity of
      chimeric allergen was determined using immunoblotting. Our results showed that
      the chimeric allergen was expressed at high level in E. coli BL21 (DE3)-codon
      plus RIL and Rosetta. In detail, this recombinant allergen was isolated from
      soluble fraction in the codon bias-adjusted strains of E. coli BL21 (DE3)-codon
      plus RIL and Rosetta. Moreover, some lower molecular weight proteins were
      observed in Rosetta, which could be related to inappropriate expression or broken
      compartments of the chimeric allergen. The immunoblotting assay confirmed that
      the IgE-specific immune reactivity of our chimeric allergen expressed in BL21
      (DE3)-codon plus RIL was significantly higher than the other strains. Our results
      showed that the expression of the chimeric allergen with high rare codons content
      in a codon bias-adjusted strain E. coli BL21 (DE3)-codon plus RIL improves the
      quality and solubility of the heterologous protein production. 

PMID- 27040823
TI  - Detection of Peste Des Petits Ruminants Virus (PPRV) Genome from Nasal Swabs of
      Dogs.
AB  - Peste des petits ruminants virus (PPRV) one of the most important viruses of
      small ruminants has a restricted host range. We report here the presence of PPRV
      virus in the nasal swabs of 3 out of 12 dogs in a routine microarray screening.
      The presence of PPRV sequence was further confirmed by PCR and sequencing. The
      sequence analysis revealed that the PPRV virus has close similarities with the
      viruses present in Indian subcontinent but was not identical to the vaccine virus
      used in India. Results suggest possible crossing of species barrier but requires
      further serological evidences. 

PMID- 27040824
TI  - L-carnosine enhanced reproductive potential of the Saccharomyces cerevisiae yeast
      growing on medium containing glucose as a source of carbon.
AB  - Carnosine is an endogenous dipeptide composed of beta-alanine and L-histidine,
      which occurs in vertebrates, including humans. It has a number of favorable
      properties including buffering, chelating, antioxidant, anti-glycation and anti
      aging activities. In our study we used the Saccharomyces cerevisiae yeast as a
      model organism to examine the impact of L-carnosine on the cell lifespan. We
      demonstrated that L-carnosine slowed down the growth and decreased the metabolic
      activity of cells as well as prolonged their generation time. On the other hand,
      it allowed for enhancement of the yeast reproductive potential and extended its
      reproductive lifespan. These changes may be a result of the reduced mitochondrial
      membrane potential and decreased ATP content in the yeast cells. However, due to
      reduction of the post-reproductive lifespan, L-carnosine did not have an
      influence on the total lifespan of yeast. In conclusion, L-carnosine does not
      extend the total lifespan of S. cerevisiae but rather it increases the yeast's
      reproductive capacity by increasing the number of daughter cells produced.

PMID- 27040825
TI  - Ageing with elegans: a research proposal to map healthspan pathways.
AB  - Human longevity continues to increase world-wide, often accompanied by decreasing
      birth rates. As a larger fraction of the population thus gets older, the number
      of people suffering from disease or disability increases dramatically, presenting
      a major societal challenge. Healthy ageing has therefore been selected by EU
      policy makers as an important priority ( http://www.healthyageing.eu/european
      policies-and-initiatives ); it benefits not only the elderly but also their
      direct environment and broader society, as well as the economy. The theme of
      healthy ageing figures prominently in the Horizon 2020 programme (
      https://ec.europa.eu/programmes/horizon2020/en/h2020-section/health-demographic
      change-and-wellbeing ), which has launched several research and innovation
      actions (RIA), like "Understanding health, ageing and disease: determinants, risk
      factors and pathways" in the work programme on "Personalising healthcare" (
      https://ec.europa.eu/research/participants/portal/desktop/en/opportunities/h2020/
      opics/693-phc-01-2014.html ). Here we present our research proposal entitled
      "ageing with elegans" (AwE) ( http://www.h2020awe.eu/ ), funded by this RIA,
      which aims for better understanding of the factors causing health and disease in
      ageing, and to develop evidence-based prevention, diagnostic, therapeutic and
      other strategies. The aim of this article, authored by the principal
      investigators of the 17 collaborating teams, is to describe briefly the
      rationale, aims, strategies and work packages of AwE for the purposes of sharing
      our ideas and plans with the biogerontological community in order to invite
      scientific feedback, suggestions, and criticism.

PMID- 27040826
TI  - Lessons from Freelancing, Lighting Design to Genetic Counseling.
AB  - Theatrical lighting design and genetic counseling may seem like antipodal career
      choices. The former was chosen from a belief in the dynamism of the theatrical
      experience, as well as love of the actual work. As I grew older, the powerful
      personal experiences of a life encompassing miscarriages, the birth of a child
      with a genetic disorder, and breast cancer profoundly directed my choice of a new
      career; one that I also love. Clearly, the day-to-day work is very different.
      However, people in both professions strive to create a transformative space for
      their respective public. Rather than being left behind, lessons learned by
      working as a freelancer have served as a source of inspiration as I have matured
      into my new career. Three specific strategies, supported by literature on career
      models, have been paramount. First, keeping an eye on the big picture encourages
      awareness of where the field of genetics and the genetic counseling job market
      are headed. That awareness leads to the advocacy necessary to achieve the
      outcomes genetic counselors want. Second, striving for continual personal growth
      keeps genetic counselors engaged and personally ready for professional changes.
      Third, networking provides the connections to make clinical and advocacy efforts
      successful, in addition to essential social support.

PMID- 27040827
TI  - "iSS-Hyb-mRMR": Identification of splicing sites using hybrid space of pseudo
      trinucleotide and pseudo tetranucleotide composition.
AB  - BACKGROUND AND OBJECTIVES: Gene splicing is a vital source of protein diversity.
      Perfectly eradication of introns and joining exons is the prominent task in
      eukaryotic gene expression, as exons are usually interrupted by introns.
      Identification of splicing sites through experimental techniques is complicated
      and time-consuming task. With the avalanche of genome sequences generated in the
      post genomic age, it remains a complicated and challenging task to develop an
      automatic, robust and reliable computational method for fast and effective
      identification of splicing sites. METHODS: In this study, a hybrid model "iSS-Hyb
      mRMR" is proposed for quickly and accurately identification of splicing sites.
      Two sample representation methods namely; pseudo trinucleotide composition
      (PseTNC) and pseudo tetranucleotide composition (PseTetraNC) were used to extract
      numerical descriptors from DNA sequences. Hybrid model was developed by
      concatenating PseTNC and PseTetraNC. In order to select high discriminative
      features, minimum redundancy maximum relevance algorithm was applied on the
      hybrid feature space. The performance of these feature representation methods was
      tested using various classification algorithms including K-nearest neighbor,
      probabilistic neural network, general regression neural network, and fitting
      network. Jackknife test was used for evaluation of its performance on two
      benchmark datasets S1 and S2, respectively. RESULTS: The predictor, proposed in
      the current study achieved an accuracy of 93.26%, sensitivity of 88.77%, and
      specificity of 97.78% for S1, and the accuracy of 94.12%, sensitivity of 87.14%,
      and specificity of 98.64% for S2, respectively. CONCLUSION: It is observed, that
      the performance of proposed model is higher than the existing methods in the
      literature so for; and will be fruitful in the mechanism of RNA splicing, and
      other research academia.

PMID- 27040828
TI  - Forced oscillation, integer and fractional-order modeling in asthma.
AB  - The purpose of this study was to evaluate the use of fractional-order (FrOr)
      modeling in asthma. To this end, three FrOr models were compared with traditional
      parameters and an integer-order model (InOr). We investigated which model would
      best fit the data, the correlation with traditional lung function tests and the
      contribution to the diagnostic of airway obstruction. The data consisted of
      forced oscillation (FO) measurements obtained from healthy (n=22) and asthmatic
      volunteers with mild (n=22), moderate (n=19) and severe (n=19) obstructions. The
      first part of this study showed that a FrOr was the model that best fit the data
      (relative distance: FrOr=4.3+/-2.4; InOr=5.1+/-2.6%). The correlation analysis
      resulted in reasonable (R=0.36) to very good (R=0.77) associations between FrOr
      parameters and spirometry. The closest associations were observed between
      parameters related to peripheral airway obstruction, showing a clear relationship
      between the FrOr models and lung mechanics. Receiver-operator analysis showed
      that FrOr parameters presented a high potential to contribute to the detection of
      the mild obstruction in a clinical setting. The accuracy [area under the Receiver
      Operating Characteristic curve (AUC)] observed in these parameters (AUC=0.954)
      was higher than that observed in traditional FO parameters (AUC=0.732) and that
      obtained from the InOr model (AUC=0.861). Patients with moderate and severe
      obstruction were identified with high accuracy (AUC=0.972 and 0.977,
      respectively). In conclusion, the results obtained are in close agreement with
      asthma pathology, and provide evidence that FO measurement associated with FrOr
      models is a non-invasive, simple and radiation-free method for the detection of
      biomechanical abnormalities in asthma.

PMID- 27040829
TI  - Design of a heart rate controller for treadmill exercise using a recurrent fuzzy
      neural network.
AB  - BACKGROUND AND OBJECTIVE: In this study, we developed a computer controlled
      treadmill system using a recurrent fuzzy neural network heart rate controller
      (RFNNHRC). Treadmill speeds and inclines were controlled by corresponding control
      servo motors. The RFNNHRC was used to generate the control signals to
      automatically control treadmill speed and incline to minimize the user heart rate
      deviations from a preset profile. METHODS: The RFNNHRC combines a fuzzy reasoning
      capability to accommodate uncertain information and an artificial recurrent
      neural network learning process that corrects for treadmill system nonlinearities
      and uncertainties. Treadmill speeds and inclines are controlled by the RFNNHRC to
      achieve minimal heart rate deviation from a pre-set profile using adjustable
      parameters and an on-line learning algorithm that provides robust performance
      against parameter variations. The on-line learning algorithm of RFNNHRC was
      developed and implemented using a dsPIC 30F4011 DSP. RESULTS: Application of the
      proposed control scheme to heart rate responses of runners resulted in smaller
      fluctuations than those produced by using proportional integra control, and
      treadmill speeds and inclines were smoother. The present experiments demonstrate
      improved heart rate tracking performance with the proposed control scheme.
      CONCLUSIONS: The RFNNHRC scheme with adjustable parameters and an on-line
      learning algorithm was applied to a computer controlled treadmill system with
      heart rate control during treadmill exercise. Novel RFNNHRC structure and
      controller stability analyses were introduced. The RFNNHRC were tuned using a
      Lyapunov function to ensure system stability. The superior heart rate control
      with the proposed RFNNHRC scheme was demonstrated with various pre-set heart
      rates.

PMID- 27040830
TI  - Amplitude-aware permutation entropy: Illustration in spike detection and signal
      segmentation.
AB  - BACKGROUND AND OBJECTIVE: Signal segmentation and spike detection are two
      important biomedical signal processing applications. Often, non-stationary
      signals must be segmented into piece-wise stationary epochs or spikes need to be
      found among a background of noise before being further analyzed. Permutation
      entropy (PE) has been proposed to evaluate the irregularity of a time series. PE
      is conceptually simple, structurally robust to artifacts, and computationally
      fast. It has been extensively used in many applications, but it has two key
      shortcomings. First, when a signal is symbolized using the Bandt-Pompe procedure,
      only the order of the amplitude values is considered and information regarding
      the amplitudes is discarded. Second, in the PE, the effect of equal amplitude
      values in each embedded vector is not addressed. To address these issues, we
      propose a new entropy measure based on PE: the amplitude-aware permutation
      entropy (AAPE). METHODS: AAPE is sensitive to the changes in the amplitude, in
      addition to the frequency, of the signals thanks to it being more flexible than
      the classical PE in the quantification of the signal motifs. To demonstrate how
      the AAPE method can enhance the quality of the signal segmentation and spike
      detection, a set of synthetic and realistic synthetic neuronal signals,
      electroencephalograms and neuronal data are processed. We compare the performance
      of AAPE in these problems against state-of-the-art approaches and evaluate the
      significance of the differences with a repeated ANOVA with post hoc Tukey's test.
      RESULTS: In signal segmentation, the accuracy of AAPE-based method is higher than
      conventional segmentation methods. AAPE also leads to more robust results in the
      presence of noise. The spike detection results show that AAPE can detect spikes
      well, even when presented with single-sample spikes, unlike PE. For multi-sample
      spikes, the changes in AAPE are larger than in PE. CONCLUSION: We introduce a new
      entropy metric, AAPE, that enables us to consider amplitude information in the
      formulation of PE. The AAPE algorithm can be used in almost every irregularity
      based application in various signal and image processing fields. We also made
      freely available the Matlab code of the AAPE.

PMID- 27040831
TI  - Temporal data representation, normalization, extraction, and reasoning: A review
      from clinical domain.
AB  - BACKGROUND AND OBJECTIVE: We live our lives by the calendar and the clock, but
      time is also an abstraction, even an illusion. The sense of time can be both
      domain-specific and complex, and is often left implicit, requiring significant
      domain knowledge to accurately recognize and harness. In the clinical domain, the
      momentum gained from recent advances in infrastructure and governance practices
      has enabled the collection of tremendous amount of data at each moment in time.
      Electronic health records (EHRs) have paved the way to making these data
      available for practitioners and researchers. However, temporal data
      representation, normalization, extraction and reasoning are very important in
      order to mine such massive data and therefore for constructing the clinical
      timeline. The objective of this work is to provide an overview of the problem of
      constructing a timeline at the clinical point of care and to summarize the state
      of-the-art in processing temporal information of clinical narratives. METHODS:
      This review surveys the methods used in three important area: modeling and
      representing of time, medical NLP methods for extracting time, and methods of
      time reasoning and processing. The review emphasis on the current existing gap
      between present methods and the semantic web technologies and catch up with the
      possible combinations. RESULTS: The main findings of this review are revealing
      the importance of time processing not only in constructing timelines and clinical
      decision support systems but also as a vital component of EHR data models and
      operations. CONCLUSIONS: Extracting temporal information in clinical narratives
      is a challenging task. The inclusion of ontologies and semantic web will lead to
      better assessment of the annotation task and, together with medical NLP
      techniques, will help resolving granularity and co-reference resolution problems.

PMID- 27040832
TI  - InterSIM: Simulation tool for multiple integrative 'omic datasets'.
AB  - BACKGROUND AND OBJECTIVE: Integrative approaches for the study of biological
      systems have gained popularity in the realm of statistical genomics. For example,
      The Cancer Genome Atlas (TCGA) has applied integrative clustering methodologies
      to various cancer types to determine molecular subtypes within a given cancer
      histology. In order to adequately compare integrative or "systems-biology"-type
      methods, realistic and related datasets are needed to assess the methods. This
      involves simulating multiple types of 'omic data with realistic correlation
      between features of the same type (e.g., gene expression for genes in a pathway)
      and across data types (e.g., "gene silencing" involving DNA methylation and gene
      expression). METHODS: We present the software application tool InterSIM for
      simulating multiple interrelated data types with realistic intra- and inter
      relationships based on the DNA methylation, mRNA gene expression, and protein
      expression from the TCGA ovarian cancer study. RESULTS: The resulting simulated
      datasets can be used to assess and compare the operating characteristics of newly
      developed integrative bioinformatics methods to existing methods. Application of
      InterSIM is presented with an example of heatmaps of the simulated datasets.
      CONCLUSIONS: InterSIM allows researchers to evaluate and test new integrative
      methods with realistically simulated interrelated genomic datasets. The software
      tool InterSIM is implemented in R and is freely available from CRAN.

PMID- 27040833
TI  - Active learning based segmentation of Crohns disease from abdominal MRI.
AB  - This paper proposes a novel active learning (AL) framework, and combines it with
      semi supervised learning (SSL) for segmenting Crohns disease (CD) tissues from
      abdominal magnetic resonance (MR) images. Robust fully supervised learning (FSL)
      based classifiers require lots of labeled data of different disease severities.
      Obtaining such data is time consuming and requires considerable expertise. SSL
      methods use a few labeled samples, and leverage the information from many
      unlabeled samples to train an accurate classifier. AL queries labels of most
      informative samples and maximizes gain from the labeling effort. Our primary
      contribution is in designing a query strategy that combines novel context
      information with classification uncertainty and feature similarity. Combining SSL
      and AL gives a robust segmentation method that: (1) optimally uses few labeled
      samples and many unlabeled samples; and (2) requires lower training time.
      Experimental results show our method achieves higher segmentation accuracy than
      FSL methods with fewer samples and reduced training effort. 

PMID- 27040834
TI  - ANAlyte: A modular image analysis tool for ANA testing with indirect
      immunofluorescence.
AB  - BACKGROUND AND OBJECTIVES: The automated analysis of indirect immunofluorescence
      images for Anti-Nuclear Autoantibody (ANA) testing is a fairly recent field that
      is receiving ever-growing interest from the research community. ANA testing
      leverages on the categorization of intensity level and fluorescent pattern of IIF
      images of HEp-2 cells to perform a differential diagnosis of important autoimmune
      diseases. Nevertheless, it suffers from tremendous lack of repeatability due to
      subjectivity in the visual interpretation of the images. The automatization of
      the analysis is seen as the only valid solution to this problem. Several works in
      literature address individual steps of the work-flow, nonetheless integrating
      such steps and assessing their effectiveness as a whole is still an open
      challenge. METHODS: We present a modular tool, ANAlyte, able to characterize a
      IIF image in terms of fluorescent intensity level and fluorescent pattern without
      any user-interactions. For this purpose, ANAlyte integrates the following: (i)
      Intensity Classifier module, that categorizes the intensity level of the input
      slide based on multi-scale contrast assessment; (ii) Cell Segmenter module, that
      splits the input slide into individual HEp-2 cells; (iii) Pattern Classifier
      module, that determines the fluorescent pattern of the slide based on the pattern
      of the individual cells. RESULTS: To demonstrate the accuracy and robustness of
      our tool, we experimentally validated ANAlyte on two different public benchmarks
      of IIF HEp-2 images with rigorous leave-one-out cross-validation strategy. We
      obtained overall accuracy of fluorescent intensity and pattern classification
      respectively around 85% and above 90%. We assessed all results by comparisons
      with some of the most representative state of the art works. CONCLUSIONS: Unlike
      most of the other works in the recent literature, ANAlyte aims at the
      automatization of all the major steps of ANA image analysis. Results on public
      benchmarks demonstrate that the tool can characterize HEp-2 slides in terms of
      intensity and fluorescent pattern with accuracy better or comparable with the
      state of the art techniques, even when such techniques are run on manually
      segmented cells. Hence, ANAlyte can be proposed as a valid solution to the
      problem of ANA testing automatization.

PMID- 27040835
TI  - A remote quantitative Fugl-Meyer assessment framework for stroke patients based
      on wearable sensor networks.
AB  - To extend the use of wearable sensor networks for stroke patients training and
      assessment in non-clinical settings, this paper proposes a novel remote
      quantitative Fugl-Meyer assessment (FMA) framework, in which two accelerometer
      and seven flex sensors were used to monitoring the movement function of upper
      limb, wrist and fingers. The extreme learning machine based ensemble regression
      model was established to map the sensor data to clinical FMA scores while the
      RRelief algorithm was applied to find the optimal features subset. Considering
      the FMA scale is time-consuming and complicated, seven training exercises were
      designed to replace the upper limb related 33 items in FMA scale. 24 stroke
      inpatients participated in the experiments in clinical settings and 5 of them
      were involved in the experiments in home settings after they left the hospital.
      Both the experimental results in clinical and home settings showed that the
      proposed quantitative FMA model can precisely predict the FMA scores based on
      wearable sensor data, the coefficient of determination can reach as high as
      0.917. It also indicated that the proposed framework can provide a potential
      approach to the remote quantitative rehabilitation training and evaluation. 

PMID- 27040836
TI  - UltraTrack: Software for semi-automated tracking of muscle fascicles in sequences
      of B-mode ultrasound images.
AB  - BACKGROUND: Dynamic measurements of human muscle fascicle length from sequences
      of B-mode ultrasound images have become increasingly prevalent in biomedical
      research. Manual digitisation of these images is time consuming and algorithms
      for automating the process have been developed. Here we present a freely
      available software implementation of a previously validated algorithm for semi
      automated tracking of muscle fascicle length in dynamic ultrasound image
      recordings, "UltraTrack". METHODS: UltraTrack implements an affine extension to
      an optic flow algorithm to track movement of the muscle fascicle end-points
      throughout dynamically recorded sequences of images. The underlying algorithm has
      been previously described and its reliability tested, but here we present the
      software implementation with features for: tracking multiple fascicles in
      multiple muscles simultaneously; correcting temporal drift in measurements;
      manually adjusting tracking results; saving and re-loading of tracking results
      and loading a range of file formats. RESULTS: Two example runs of the software
      are presented detailing the tracking of fascicles from several lower limb muscles
      during a squatting and walking activity. CONCLUSION: We have presented a software
      implementation of a validated fascicle-tracking algorithm and made the source
      code and standalone versions freely available for download.

PMID- 27040837
TI  - Probabilistic atlas prior for CT image reconstruction.
AB  - BACKGROUND AND OBJECTIVES: In computed tomography (CT), statistical iterative
      reconstruction (SIR) approaches can produce images of higher quality compared to
      the conventional analytical methods such as filtered backprojection (FBP)
      algorithm. Effective noise modeling and possibilities to incorporate priors in
      the image reconstruction problem are the main advantages that lead to continuous
      development of SIR methods. Oriented by low-dose CT requirements, several methods
      are recently developed to obtain a high-quality image reconstruction from down
      sampled or noisy projection data. In this paper, a new prior information obtained
      from probabilistic atlas is proposed for low-dose CT image reconstruction.
      METHODS: The proposed approach consists of two main phases. In learning phase, a
      dataset of images obtained from different patients is used to construct a 3D
      atlas with Laplacian mixture model. The expectation maximization (EM) algorithm
      is used to estimate the mixture parameters. In reconstruction phase, prior
      information obtained from the probabilistic atlas is used to construct the cost
      function for image reconstruction. RESULTS: We investigate the low-dose imaging
      by considering the reduction of X-ray beam intensity and by acquiring the
      projection data through a small number of views or limited view angles.
      Experimental studies using simulated data and chest screening CT data demonstrate
      that the probabilistic atlas prior is a practically promising approach for the
      low-dose CT imaging. CONCLUSIONS: The prior information obtained from
      probabilistic atlas constructed from earlier scans of different patients is
      useful in low-dose CT imaging.

PMID- 27040838
TI  - PCA-based polling strategy in machine learning framework for coronary artery
      disease risk assessment in intravascular ultrasound: A link between carotid and
      coronary grayscale plaque morphology.
AB  - BACKGROUND AND OBJECTIVE: Percutaneous coronary interventional procedures need
      advance planning prior to stenting or an endarterectomy. Cardiologists use
      intravascular ultrasound (IVUS) for screening, risk assessment and stratification
      of coronary artery disease (CAD). We hypothesize that plaque components are
      vulnerable to rupture due to plaque progression. Currently, there are no standard
      grayscale IVUS tools for risk assessment of plaque rupture. This paper presents a
      novel strategy for risk stratification based on plaque morphology embedded with
      principal component analysis (PCA) for plaque feature dimensionality reduction
      and dominant feature selection technique. The risk assessment utilizes 56
      grayscale coronary features in a machine learning framework while linking
      information from carotid and coronary plaque burdens due to their common genetic
      makeup. METHOD: This system consists of a machine learning paradigm which uses a
      support vector machine (SVM) combined with PCA for optimal and dominant coronary
      artery morphological feature extraction. Carotid artery proven intima-media
      thickness (cIMT) biomarker is adapted as a gold standard during the training
      phase of the machine learning system. For the performance evaluation, K-fold
      cross validation protocol is adapted with 20 trials per fold. For choosing the
      dominant features out of the 56 grayscale features, a polling strategy of PCA is
      adapted where the original value of the features is unaltered. Different
      protocols are designed for establishing the stability and reliability criteria of
      the coronary risk assessment system (cRAS). RESULTS: Using the PCA-based machine
      learning paradigm and cross-validation protocol, a classification accuracy of
      98.43% (AUC 0.98) with K=10 folds using an SVM radial basis function (RBF) kernel
      was achieved. A reliability index of 97.32% and machine learning stability
      criteria of 5% were met for the cRAS. CONCLUSIONS: This is the first Computer
      aided design (CADx) system of its kind that is able to demonstrate the ability of
      coronary risk assessment and stratification while demonstrating a successful
      design of the machine learning system based on our assumptions.

PMID- 27040839
TI  - Reliable and stable computer-aided diagnosis systems for images.

PMID- 27040840
TI  - The importance of strigolactone transport regulation for symbiotic signaling and
      shoot branching.
AB  - MAIN CONCLUSION: This review presents the role of strigolactone transport in
      regulating plant root and shoot architecture, plant-fungal symbiosis and the
      crosstalk with several phytohormone pathways. The authors, based on their data
      and recently published results, suggest that long-distance, as well local
      strigolactone transport might occur in a cell-to-cell manner rather than via the
      xylem stream. Strigolactones (SLs) are recently characterized carotenoid-derived
      phytohormones. They play multiple roles in plant architecture and, once exuded
      from roots to soil, in plant-rhizosphere interactions. Above ground SLs regulate
      plant developmental processes, such as lateral bud outgrowth, internode
      elongation and stem secondary growth. Below ground, SLs are involved in lateral
      root initiation, main root elongation and the establishment of the plant-fungal
      symbiosis known as mycorrhiza. Much has been discovered on players and patterns
      of SL biosynthesis and signaling and shown to be largely conserved among
      different plant species, however little is known about SL distribution in plants
      and its transport from the root to the soil. At present, the only characterized
      SL transporters are the ABCG protein PLEIOTROPIC DRUG RESISTANCE 1 from Petunia
      axillaris (PDR1) and, in less detail, its close homologue from Nicotiana tabacum
      PLEIOTROPIC DRUG RESISTANCE 6 (PDR6). PDR1 is a plasma membrane-localized SL
      cellular exporter, expressed in root cortex and shoot axils. Its expression level
      is regulated by its own substrate, but also by the phytohormone auxin, soil
      nutrient conditions (mainly phosphate availability) and mycorrhization levels.
      Hence, PDR1 integrates information from nutrient availability and hormonal
      signaling, thus synchronizing plant growth with nutrient uptake. In this review
      we discuss the effects of PDR1 de-regulation on plant development and
      mycorrhization, the possible cross-talk between SLs and other phytohormone
      transporters and finally the need for SL transporters in different plant species.

PMID- 27040841
TI  - miR393 contributes to the embryogenic transition induced in vitro in Arabidopsis
      via the modification of the tissue sensitivity to auxin treatment.
AB  - MAIN CONCLUSION: miR393 was found to control embryogenic transition in somatic
      cells in Arabidopsis via control of the TIR1 and AFB2 auxin receptors genes of
      the F-box family. miR393 molecules are believed to regulate the expression of the
      auxin receptors of the TAAR clade. Considering the central role of auxin in the
      induction of somatic embryogenesis (SE) in plant explants cultured in vitro, the
      involvement of miR393 in the embryogenic transition of somatic cells has been
      hypothesised. To verify this assumption, the reporter, overexpressor and mutant
      lines in genes encoded MIR393 and TIR1/AFB proteins of the F-box family were
      analysed during SE in Arabidopsis. Expression profiling of MIR393a and MIR393b,
      mature miR393 and the target genes (TIR1, AFB1, AFB2, AFB3) were investigated in
      explants undergoing SE. In addition, the embryogenic potential of various
      genotypes with a modified activity of the MIR393 and TIR1/AFB targets was
      evaluated. The distinct increase in the accumulation of miR393 that was coupled
      with a notable down-regulation of TIR1 and AFB2 targets was observed at the early
      phase of SE induction. Relevant to this observation, the GUS/GFP monitored
      expression of MIR393, TIR1 and AFB2 transcripts was localised in explant tissue
      undergoing SE induction. The results suggest the miR393-mediated regulation of
      TIR1 and AFB2 during embryogenic transition induced in Arabidopsis and a
      modification of the explant sensitivity to auxin treatment is proposed as
      underlying this regulatory pathway.

PMID- 27040842
TI  - Does septoplasty change the dimensions of compensatory hypertrophy of the middle
      turbinate?
AB  - OBJECTIVE: To measure the dimensions of compensatory hypertrophy of the middle
      turbinate in patients with nasal septal deviation, before and after septoplasty.
      METHODS: The mucosal and bony structures of the middle turbinate and the angle of
      the septum were measured using radiological analysis before septoplasty and at
      least one year after septoplasty. All pre- and post-operative measurements of the
      middle turbinate were compared using the paired sample t-test and Wilcoxon rank
      sum test. RESULTS: The dimensions of bony and mucosal components of the middle
      turbinate on concave and convex sides of the septum were not significantly
      changed by septoplasty. There was a significant negative correlation after
      septoplasty between the angle of the septum and the middle turbinate total area
      on the deviated side (p = 0.033). CONCLUSION: The present study findings suggest
      that compensatory hypertrophy of the middle turbinate is not affected by
      septoplasty, even after one year.

PMID- 27040843
TI  - Evidence of metabolically active but non-culturable Listeria monocytogenes in
      long-term growth at 10  degrees C.
AB  - Cultures of Listeria monocytogenes at low temperatures (10  degrees C) in a broth
      model revealed long-term survival at about 0.04% cell density in relation to the
      log phase. In contrast, direct viable counts and PMA real-time PCR data suggested
      that 50% and 1% of the population retain membrane integrity, respectively. To
      elucidate the observed difference, the metabolic activity of the bacterial
      population was investigated by multiparametric flow cytometry, including the
      assessment of membrane integrity, reductase activity, as well as forward and side
      scatter properties. These analyses were complemented by 16S rRNA real-time PCR.
      The majority of the cells retained their membrane integrity and reductase
      activity until day 29. On day 42, 48.00 +/- 4.00% (L. monocytogenes strain 3251)
      and 68.67 +/- 3.74% (L. monocytogenes strain 535) of the cells had intact
      membranes, whereas 57.23 +/- 1.85% (strain 3251) and 74.97 +/- 3.01% (strain 535)
      exhibited high reductase activity. On day 42, mean 16S rRNA copy numbers of 3.98
      +/- 1.37 (membrane integrity) and 3.86 +/- 1.32 (reductase activity) remained per
      intact or active cell. Our data suggest the transition of L. monocytogenes into a
      state of metabolic dormancy during long-term culture at low temperature. 

PMID- 27040844
TI  - Diffuse malignant mesothelioma and synchronous lung cancer: A clinicopathological
      study of 18 cases.
AB  - OBJECTIVES: To examine the clinicopathologic characteristics of individuals with
      diffuse malignant mesothelioma (DMM) occurring concurrently with lung cancer
      (LC). MATERIALS AND METHODS: A database of approximately 3800 patients with DMM
      was reviewed, from which 18 patients (0.5%) who had synchronous LC were
      identified. The clinicopathologic features, as well as the occupational exposure
      history and fiber burden analysis data were examined. RESULTS: The patient median
      age was 68 years (range 58-84 years). Of the 18 patients (14 male, 4 female), 11
      (61%) had epithelial, 5 (28%) had biphasic, and 2 (11%) had sarcomatoid DMM, with
      the majority (16 cases; 89%) originating in the pleura and only 2 were
      peritoneal. Among the histologic types of LC, adenocarcinoma was most frequent
      (12 cases; 67%), while 5 cases of squamous cell carcinoma, and 1 case of small
      cell carcinoma were observed. Three patients also had a history of prior
      malignancy (1 with testicular seminoma and bladder carcinoma and 2 with prostate
      carcinoma). Fifteen patients had a positive smoking history. All but 3 had
      documented asbestos exposure. Three had histologic features of asbestosis.
      Mineral analysis performed in 8 showed an elevated asbestos fiber burden in 4
      (22%). Amosite was detected in 4 patients, crocidolite in 3, and non-commercial
      amphiboles in 5. CONCLUSION: The finding of simultaneous carcinoma of the lung
      and DMM is distinctly unusual. The majority of patients are male smokers with
      pleural epithelial DMM and lung adenocarcinoma. This study represents the largest
      cohort of patients reported to date with synchronous malignant mesothelioma and
      lung cancer, and we propose guidelines for making a diagnosis of synchronous
      malignant mesothelioma and primary lung cancer.

PMID- 27040845
TI  - Patients' preferred and perceived roles in making decisions about adjuvant
      chemotherapy for non-small-cell lung cancer.
AB  - BACKGROUND: People with cancer have varying preferences for involvement in
      decision-making between active, collaborative and passive roles. We sought the
      preferred and perceived involvement in decision-making among patients considering
      adjuvant chemotherapy (ACT) after resection of early non-small cell lung cancer
      (NSCLC). METHODS: Patients considering ACT for NSCLC were asked to complete a
      self-administered questionnaire at baseline and 6 months. Preferred and perceived
      decision-making roles were assessed by the Control Preferences Scale (CPS). We
      examined differences between preferred and perceived roles, differences in
      preferred roles over time, determinants of preferences, and differences in
      treatment preferences between patients preferring active and less active roles.
      RESULTS: 98 patients completed the baseline questionnaire; 75 completed the 6
      month questionnaire. Most patients were male (55%) with a median age of 64 years
      (range, 43-79 years). Preferred role in decision-making at baseline (n=98) was
      active in 27%, collaborative in 47%, and passive in 27%. Perceived decision
      making roles matched the preferred role in 79% of patients. Individuals' role
      preferences often varied between baseline and 6 months, but there was no
      consistent direction to the change (25% changed preference to more active
      involvement, 22% to less active). Preferring a more active role was associated
      with university education (OR 2.9, p=0.02), deciding not to have ACT (OR 5.0,
      p<0.01), and worse health-related quality of life (HRQL) during ACT: physical
      well-being (OR 4.4, p=0.05), overall well-being (OR 5.5, p=0.02), sleep (OR 8.4,
      p<0.01) and shortness of breath (OR 7.6, p=0.01). Patients who preferred an
      active decision-making role judged larger survival benefits necessary to make ACT
      worthwhile than those preferring a passive role. CONCLUSION: Most patients with
      resected NSCLC preferred and perceived a collaborative role in decision-making
      about ACT. Clinicians should elicit and consider patients' preferences for
      involvement in decision-making when discussing ACT for NSCLC.

PMID- 27040846
TI  - Successful treatment with ceritinib after crizotinib induced hepatitis.
AB  - We report two cases of acute hepatitis induced by crizotinib in patients with ALK
      rearranged non-small cell lung cancer (NSCLC) who were treated after by a second
      generation of ALK inhibitor without any incident. These cases suggest that
      ceritinib could be used as an alternative agent when crizotinib is responsible
      for hepatitis. 

PMID- 27040847
TI  - Leisure-time physical activity and lung cancer risk: A systematic review and meta
      analysis.
AB  - OBJECTIVES: We conducted a systematic review and meta-analysis of the association
      between recreational physical activity and lung cancer risk to update previous
      analyses and to examine population subgroups of interest defined by smoking
      status and histology. MATERIALS AND METHODS: We searched the PubMed database for
      studies up to May 2015. Individual study characteristics were abstracted
      including study design, number of cases, assessment of recreational physical
      activity and type and level of adjustment for confounding factors. Combined
      effect estimates were calculated for the overall associations and across
      subgroups of interest. RESULTS: We identified 28 studies that were eligible for
      inclusion in the meta-analysis. The overall analysis indicated an inverse
      association between recreational physical activity and lung cancer risk (Relative
      Risk (RR), 0.76; 95% Confidence Interval (CI), 0.69-0.85, p-value: <0.001).
      Similar inverse associations with risk were also noted for all evaluated
      histological subtypes, including adenocarcinoma (RR, 0.80; 95% CI, 0.72-0.88),
      squamous (RR, 0.80; 95% CI, 0.71-0.90) and small cell (RR, 0.79; 95% CI, 0.66
      0.94). When we examined effects by smoking status, inverse associations between
      recreational physical activity and lung cancer risk were observed among former
      (RR, 0.77; 95% CI, 0.69-0.85) and current smokers (RR, 0.77; 95% CI, 0.72-0.83),
      but not among never smokers (RR, 0.96; 95% CI, 0.79-1.18). CONCLUSION: Results
      from this meta-analysis suggest that regular recreational physical activity may
      be associated with reduced risk of lung cancer. Only four studies examining never
      smokers were identified, suggesting the need for additional research in this
      population.

PMID- 27040848
TI  - Geographic variation in the use of adjuvant therapy among elderly patients with
      resected non-small cell lung cancer.
AB  - OBJECTIVES: The purpose of this study was to assess to what extent geographic
      variation in adjuvant treatment for non-small cell lung cancer (NSCLC) patients
      would remain, after controlling for patient and area-level characteristics.
      MATERIALS AND METHODS: A retrospective cohort of 18,410 Medicare beneficiaries
      with resected, stage I-IIIA NSCLC was identified from the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare linked database. Adjuvant therapies
      were classified as adjuvant chemotherapy (ACT), postoperative radiation therapy
      (PORT), or no adjuvant therapy. Predicted treatment probabilities were estimated
      for each patient given their clinical, demographic, and area-level
      characteristics with multivariate logistic regression. Area Treatment Ratios were
      used to estimate the propensity of patients in a local area to receive an
      adjuvant treatment, controlling for characteristics of patients in the area.
      Areas were categorized as low-, mid- and high-use and mapped for two
      representative SEER registries. RESULTS: Overall, 10%, 12%, and 78% of patients
      received ACT, PORT and no adjuvant therapy, respectively. Age, sex, stage, type
      and year of surgery, and comorbidity were associated with adjuvant treatment use.
      Even after adjusting for patient characteristics, substantial geographic
      treatment variation remained. High- and low-use areas were tightly juxtaposed
      within and across SEER registries, often within the same county. In some local
      areas, patients were up to eight times more likely to receive adjuvant therapy
      than expected, given their characteristics. On the other hand, almost a quarter
      of patients lived in local areas in which patients were more than three times
      less likely to receive ACT than would be predicted. CONCLUSION: Controlling for
      patient and area-level covariates did not remove geographic variation in adjuvant
      therapies for resected NSCLC patients. A greater proportion of patients were
      treated less than expected, rather than more than expected. Further research is
      needed to better understand its causes and potential impact on outcomes.

PMID- 27040849
TI  - Afatinib-associated Stevens-Johnson syndrome in an EGFR-mutated lung cancer
      patient.
AB  - INTRODUCTION: Afatinib is a tyrosine kinase inhibitor (TKI), that has been
      approved for treating patients with epidermal growth factor receptor (EGFR)
      mutated advanced non-small-cell lung cancer (NSCLC). Stevens-Johnson syndrome
      (SJS) related to EGFR directed TKIs is a rare adverse event. CASE PRESENTATION:
      We report a case of a 79-year-old white female with EGFR-mutated, metastatic non
      small-cell lung cancer treated with afatinib as first-line palliative treatment,
      who developed a SJS after two months of treatment. Discontinuation of the TKI and
      systemic glucocorticoid treatment led to improvement of symptoms and recovery.
      CONCLUSION: Severe adverse cutaneous drug reactions that predominantly involve
      the skin and mucous membranes during treatment with afatinib should alert
      clinicians to suspect SJS and react appropriately.

PMID- 27040850
TI  - Antibody 1A4 with routine immunohistochemistry demonstrates high sensitivity for
      ALK rearrangement screening of Chinese lung adenocarcinoma patients: A single
      center large-scale study.
AB  - OBJECTIVES: The rearrangement of echinoderm microtubule-associated protein-like 4
      analplastic lymphoma kinase (EML4-ALK) in non-small cell lung cancer (NSCLC)
      cells might be a promising therapeutic target. However, the low positive rate
      seeks a reliable and cost-effective method for ALK rearrangement prescreening.
      This study aimed to evaluate the application of a novel primary antibody 1A4 for
      routine ALK immunohistochemistry (IHC) test. MATERIALS AND METHODS: Primary
      antibody 1A4 and D5F3 were used for the screening of 595 formalin-fixed, paraffin
      embedded tissues of consecutive patients with lung adenocarcinoma for ALK
      positive candidates. Ventana detection system and fluorescence in-situ
      hybridization (FISH) were used as reference methods. RESULTS: Among 595 cases,
      the protein expression statuses of 1A4 were 3+ (18), 2+ (50), 1+ (153), and 0+
      (374), and those of D5F3 were 3+ (17), 2+ (18), 1+ (20), and 0+ (540). Ventana
      detection system and FISH test results were successfully obtained from 482 cases.
      A total of 298 specimens with 1A4 (-) showed 100% concordance with standard FISH
      results. All 58 FISH (+) cases were identified by antibody 1A4. Meanwhile, 14 and
      5 were missed by antibody D5F3 with routine IHC and Ventana system, respectively.
      1A4 with routine IHC had better sensitivity (100%, 75.9%, and 91.4%,
      respectively), but lower specificity (70.3%, 99.8%, and 100%, respectively), than
      D5F3 with routine IHC and Ventana system. CONCLUSION: The novel antibody 1A4 used
      as a prescreening method may help to reduce the false-negative rearranged ALK
      status if FISH or reverse transcription polymerase chain reaction results were
      used for validation.

PMID- 27040851
TI  - Timing in initiating lung cancer treatment after bronchoscopy in France: Study
      from medico-administrative database.
AB  - BACKGROUND: Time-to-treatment of cancer is becoming a serious political and
      social issue. A greater understanding of the timeframes involved in cancer care
      is needed to reduce inequalities in access to care caused by delays. OBJECTIVE:
      To describe time delays in each phase of lung cancer treatment after
      bronchoscopy. METHOD: Using the international classification of diseases and
      medical procedures codes, from national hospital discharge database we selected
      patients newly diagnosed for Lung cancer in 2009-2010 who had undergone
      treatment. RESULTS: We included 14,596 patients. Median times from bronchoscopy
      to 1) neo-adjuvant chemotherapy and to surgery in patients with surgical pathway
      were 34d (Q25=22; Q75=47) and 44d (Q25=26; Q75=82), respectively, 2) chemotherapy
      and to radiotherapy in patients with non-surgical pathway, were 33d (Q25=22;
      Q75=49) and 88d (Q25=46; Q75=162) respectively, 3) first treatment irrespective
      of pathway and treatment combination was 34d (Q25=22; Q75=50). Time to first
      treatment was significantly higher with age and with the status of the first care
      center. It was longer in most northern regions and in overseas districts and
      shorter in southern and eastern regions of the country. CONCLUSION: To our
      knowledge, this is the first study based on medico-administrative database
      describing time to first treatment after bronchoscopy in patients suffering from
      lung cancer in France. It could inform decision-making on guidelines on times to
      access lung cancer treatment.

PMID- 27040852
TI  - Estimation of the pathological invasive size of pulmonary adenocarcinoma using
      high-resolution computed tomography of the chest: A consideration based on lung
      and mediastinal window settings.
AB  - OBJECTIVES: Since the proposal of the new classification of pulmonary
      adenocarcinoma (PADC), the size of pathological invasion has become more
      important. We aimed to determine whether high-resolution computed tomography
      (HRCT) could be used to preoperatively evaluate PADC invasive size. METHODS: We
      investigated 360 complete resected cT1a-1b-2aN0 PADCs. We examined the
      correlation of pathological invasive size with three HRCT parameters [whole tumor
      dimension in the lung window (LD), consolidation dimension in the lung window
      (CD), and tumor dimension in the mediastinal window (MD)]. HRCT prediction of an
      invasive size of <=5 mm was determined using receiver operating characteristic
      curve analysis. RESULTS: Pathological invasive size correlated well with both CD
      (r(2)=0.710) and MD (r(2)=0.743) comparably, and moderately with LD (r(2)=0.514).
      CD and MD tended to be slightly larger and smaller, respectively, than the actual
      invasive size. Invasive size roughly approximated to MD+3mm, and an invasive size
      of <=5 mm was best predicted by MD, followed by CD. MD of <=2 mm and 0mm
      predicted an invasive size of <=5 mm with 64.1% and 47.4% sensitivity and 96.5%
      and 98.9% specificity, respectively. Lymphovascular invasion was best predicted
      by MD followed by CD. Pleural invasion and lymph node metastasis was predicted
      well by both MD and CD. CONCLUSION: Preoperative estimation of the invasive size
      of PADC and evaluation of other parameters of invasiveness were possible using
      MD. This approach using HRCT may play a complementary role in more thorough
      clinical staging of PADC.

PMID- 27040853
TI  - ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non
      small cell lung cancer models.
AB  - OBJECTIVES: The epidermal growth factor receptor (EGFR) abnormalities including
      amplification, mutation, and overexpression are frequent in non-small cell lung
      cancer (NSCLC). We investigated in vitro and in vivo antitumor activity of ER2, a
      novel human anti-EGFR monoclonal antibody, in NSCLC. METHODS: A panel of NSCLC
      cell lines (A549, H460, H322, H358, H1299, HCC827, PC9, H1975, and PC9-GR) was
      used to evaluate in vitro antitumor activity of ER2 and cetuximab. The inhibitory
      effects of ER2 and cetuximab on downstream signaling were assessed by western
      blot. Secreted VEGF was measured by Human VEGF Quantikine ELISA kit. Antitumor
      effects of ER2 and cetuximab as single agents and in combination with cisplatin
      were evaluated in H322, HCC827 and A549 xenograft models. RESULTS: ER2
      efficiently inhibits EGFR and its downstream signaling molecules including Akt
      and Erk1/2 in NSCLC cell lines with wild-type or mutant EGFR. ER2 inhibited cell
      viability of H322, HCC827 and A549 cells in a dose-dependent manner by inducing
      cell cycle arrest and apoptosis. Also, ER2 suppressed EGF-stimulated VEGF
      production as efficiently as cetuximab in H322, HCC827 and A549 cells. Moreover,
      ER2 alone and in combination with cisplatin showed a significant anti-tumor
      efficacy in xenograft mouse models. CONCLUSION: Taken together, ER2 has
      significant anti-tumor activity in in vitro and in vivo NSCLC models, suggesting
      a rationale for clinical development of ER2 in NSCLC.

PMID- 27040854
TI  - Epidermal growth factor receptor (EGFR) mutations in small cell lung cancers: Two
      cases and a review of the literature.
AB  - Activating mutations in the epidermal growth factor receptor (EGFR) gene are
      exceedingly rare in small cell lung cancer (SCLC). We present two cases of SCLC
      harboring EGFR mutations, one in an 82 year-old male smoker with a combined SCLC
      and adenocarcinoma with a novel D855H point mutation in exon 21, and the second
      in a 68 year-old female never smoker with the L858R point mutation in exon 21.
      The cases, accompanied by a review of the literature, highlight the importance of
      integration of clinicopathologic considerations and adherence to recently
      promulgated Guideline recommendations for molecular testing in lung cancer. 

PMID- 27040855
TI  - BE-POSITIVE: Beyond progression after tyrosine kinase inhibitor in EGFR- positive
      non small cell lung cancer patients: Results from a multicenter Italian
      observational study.
AB  - OBJECTIVES: Non-small-cell-lung-cancer (NSCLC) patients harbouring epidermal
      growth factor receptor (EGFR) mutations develop drug resistance after 9-12 months
      of EGFR tyrosine kinase inhibitors (TKIs) therapy pointing out the issue of the
      second-line treatment choice. MATERIALS AND METHODS: From June 2009 until May
      2013 patients affected by advanced NSCLC harbouring EGFR mutations receiving
      first-line TKI were collected mainly retrospectively in 24 Italian Centers.
      Primary objective was to describe the percentage of EGFR mutated patients
      receiving second-line therapy after progression to first-line EGFR-TKIs assessing
      the type, the activity in terms of objective response rate (ORR), efficacy in
      terms of progression free survival (PFS) and overall survival (OS), and safety of
      second-line treatment. Secondary objective was to describe the efficacy of first
      line EGFR-TKIs. RESULTS: 312 patients were included. Most of them were females
      (203, 65.1%), never smokers (200, 64.1%), with adenocarcinoma histology (290,
      92.9%). The most common mutations were EGFR exon 19 deletion and L858R, detected
      in 186 and 97 cases (59.6% and 31.1%), respectively. At data cut-off, 274
      patients (95.1%) received any second-line treatment (including best supportive
      care or local treatments only). A total of 163 patients received second-line
      systemic therapy with an ORR of 20.9% (95% CI:14.62-27.10), a median PFS and OS
      of 4.7 (95% CI:3.81-5.26) and 24.5 (95% CI:21.65-27.37) months, respectively.
      Grade 3-4 hematological and non-hematological toxicities were reported in 9% and
      6.3% of 144 patients treated with chemotherapy while non-hematological toxicity
      was reported in 4 cases of the 17 patients receiving second-line target agents.
      CONCLUSIONS: BE-Positive is the first multicenter observational study reporting
      outcomes of therapies in a "real-life Caucasian EGFR-mutated population",
      highlighting the need of further researches about new treatment strategies in
      this setting.

PMID- 27040856
TI  - Survival outcomes and incidence of brain recurrence in high-grade neuroendocrine
      carcinomas of the lung: Implications for clinical practice.
AB  - BACKGROUND: Among patients with advanced high-grade neuroendocrine carcinoma
      (HGNEC) of the lung, the optimal therapeutic management is much less established
      for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung
      cancers (SCLCs). We evaluated the survival outcomes and incidence of brain
      recurrence of advanced LCNECs, and compared them with those of a population of
      SCLCs matched by stage. MATERIALS AND METHODS: Forty-eight unresected stage III
      HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs)
      were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy
      with or without thoracic radiotherapy (TRT) and/or prophylactic cranial
      irradiation (PCI) was investigated. RESULTS: Overall response was significantly
      lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6%
      respectively, P=0.004) and stage IV (43.3% vs 64.5%, respectively, P=0.04).
      Similarly, an inferior outcome was observed in terms of progression-free survival
      (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however,
      reached significance only for stage III disease (median: 5.6 vs 8.9 months,
      P=0.06 and 10.4 vs 17.6 months, P=0.03 for PFS and OS, respectively). In the lack
      of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and
      48% of still living stage III and IV patients, respectively, developed brain
      metastases at 18 months. CONCLUSION: Patients with advanced LCNECs are at high
      risk for brain recurrence. Unresected stage III LCNECs treated with platinum
      etoposide with or without TRT bear a dismal prognosis, when compared indirectly
      with SCLC counterparts. Randomized trials should evaluate whether PCI could
      improve survival of advanced LCNECs.

PMID- 27040857
TI  - Predicting death from surgery for lung cancer: A comparison of two scoring
      systems in two European countries.
AB  - OBJECTIVES: Current British guidelines advocate the use of risk prediction scores
      such as Thoracoscore to estimate mortality prior to radical surgery for non-small
      cell lung cancer (NSCLC). A recent publication used the National Lung Cancer
      Audit (NLCA) to produce a score to predict 90 day mortality (NLCA score). The aim
      of this study is to validate the NLCA score, and compare its performance with
      Thoracoscore. MATERIALS AND METHODS: We performed an internal validation using
      2858 surgical patients from NLCA and an external validation using 3191 surgical
      patients from the Danish Lung Cancer Registry (DLCR). We calculated the
      proportion that died within 90 days of surgery. The discriminatory power of both
      scores was assessed by a receiver operating characteristic (ROC) and an area
      under the curve (AUC) calculation. RESULTS: Ninety day mortality was 5% in both
      groups. AUC values for internal and external validation of NLCA score and
      validation of Thoracoscore were 0.68 (95% CI 0.63-0.72), 0.60 (95% CI 0.56-0.65)
      and 0.60 (95% CI 0.54-0.66) respectively. Post-hoc analysis was performed using
      NLCA records on 15554 surgical patients to derive summary tables for 30 and 90
      day mortality, stratified by procedure type, age and performance status.
      CONCLUSIONS: Neither score performs well enough to be advocated for individual
      risk stratification prior to lung cancer surgery. It may be that additional
      physiological parameters are required; however this is a further project. In the
      interim we propose the use of our summary tables that provide the real-life range
      of mortality for lobectomy and pneumonectomy.

PMID- 27040858
TI  - EGFR, KRAS and ROS1 variants coexist in a lung adenocarcinoma patient.
AB  - The c-ros oncogene 1 (ROS1) fusion is almost mutually exclusive to epidermal
      growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or Kirsten rat
      sarcoma viral oncogene homolog (KRAS) mutation in non-small cell lung cancer
      (NSCLC), and it is not seen in the literature for patients to exhibit three
      mutations. The present study reported a case of a 53-year-old male diagnosed with
      adenocarcinoma, exhibiting combined EGFR, KRAS mutations and ROS1 rearrangement.
      At the first line therapy, the patient was treated with crizotinib because of the
      KRAS mutation that is a known resistant factor of EGFR-TKI resistance, but no
      responsive. At the second line therapy, EGFR-TKI Icotinib revealed a good
      response until now. To the best of to our knowledge, this is the first case
      report of a patient with concurrent EGFR, KRAS mutations and ROS1 fusion. This
      patient had an excellent response to Icotinib but not crizotinib, suggesting that
      the EGFR mutation was the oncogenic driver but ROS1 fusion and KRAS mutation not.

PMID- 27040859
TI  - Maternal mental well-being during pregnancy and glucocorticoid receptor gene
      promoter methylation in the neonate.
AB  - Maternal mental health during pregnancy has been linked to health outcomes in
      progeny. Mounting evidence implicates fetal "programming" in this process,
      possibly via epigenetic disruption. Maternal mental health has been associated
      with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C,
      member 1 [NR3C1]) in the neonate; however, most studies have been small (n < 100)
      and have failed to control for multiple testing in the statistical analysis. The
      Barwon Infant Study is a population-derived birth cohort with antenatal
      recruitment. Maternal depression and anxiety were assessed using the Edinburgh
      Postnatal Depression Scale and psychological distress using the Perceived Stress
      Scale. NR3C1 cord blood methylation levels were determined using Sequenom
      MassArray for 481 participants. Maternal psychological distress and anxiety were
      associated with a small increase in neonate NR3C1 methylation at specific CpG
      sites, thus replicating some previous findings. However, associations were only
      nominally significant and did not remain after correction for the number of CpG
      sites and exposures investigated. As the largest study to explore the
      relationship between maternal well-being and offspring NR3C1 cord blood
      methylation, our results highlight the need for caution when interpreting
      previous findings in this area. Future studies must ensure they are adequately
      powered to detect the likely small effect sizes while controlling for multiple
      testing.

PMID- 27040860
TI  - Silver(I)-Catalyzed Tandem Sigamatropic Rearrangement/1,3-H Shift/6pi Aza
      electrocyclization of N-Propargylic Hydrazones: A Mild Synthetic Route to 1,6
      Dihydropyridazines.
AB  - A highly efficient AgOTf catalyzed [3,3] sigmatropic rearrangement/1,3-H
      shift/6pi aza-electrocyclization cascade reaction of N-propargylic hydrazones has
      been developed. This method provides a new mild synthetic route to various
      polysubstituted 1,6-dihydropyridazines including the 3-CF3-substituted ones with
      high selectivity.

PMID- 27040861
TI  - Safety and efficacy of dipeptidyl peptidase-4 inhibitors vs sulfonylurea in
      metformin-based combination therapy for type 2 diabetes mellitus: Systematic
      review and meta-analysis.
AB  - PURPOSE: The purpose of this study was to compare the safety and efficacy of DPP
      4 inhibitors versus sulfonylurea as adjunctive second-line therapy in patients
      with type 2 diabetes mellitus, inadequately controlled with metformin mono
      therapy. SOURCES: A systematic review of published randomized controlled trials
      (RCTs) was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Two
      reviewers independently selected the studies, extracted the data and assessed the
      risk of bias. Clinical outcomes were cardiovascular events, HbA1c % change from
      baseline, body weight and hypoglycemic event rate. A direct comparison meta
      analysis using a random effect model was conducted to calculate mean differences
      in treatment effects and risk ratio between DPP-4 inhibitors and sulfonylurea.
      PRINCIPLE FINDINGS: Ten RCTs on adult patients with type 2 diabetes and
      inadequate glycemic control were included in the final analysis. DPP-4 inhibitors
      compared to sulfonylureas produced a non-significant difference in HbA1c% change
      in 10,139 subjects, whereas a significant decrease in the rate of hypoglycemic
      events was observed in favor of DPP-4 inhibitors (RR= 0.12; P<0.00001) involving
      10,616 patients, with at least one hypoglycemic event during the follow-up period
      (12-104 weeks). Body weight decreased by 2.2 kg (95% CI 1.7-2.7) with DPP-4
      inhibitors, compared with sulfonylureas. There were insufficient data to assess a
      difference in the risk for cardiovascular events. CONCLUSION: The review shows
      that, in terms of clinical efficacy, there is no significant difference between
      DPP4-inhibitors and sulfonylurea when either is added to metformin mono-therapy.
      In contrast, the safety assessment analysis showed a significant decrease in the
      risk of hypoglycemic events in patients using DPP4-inhibitors.

PMID- 27040862
TI  - Is resveratrol therapeutic when used to treat allergic rhinitisinitis in rats?
AB  - PURPOSE: Resveratrol has anti-infective, anti-inflammatory and antioxidant
      activities. The purpose of this study was to determine the effect of resveratrol
      in a rat experimental model of allergic rhinitis (AR). METHODS: Wistar albino
      rats were divided into three groups: control (n=7), AR with no treatment
      (AR+NoTr, n=7) and AR with resveratrol treatment (AR+Res, n=7). For AR+Res, AR
      was induced and resveratrol given on days 21-28. On day 28, the total blood IgE
      levels were measured. Allergic symptoms (sneezing, nose-rubbing, eye lacrimation
      and nasal congestion) were scored on a 0-3 point scale, and histopathological
      changes in the nasal mucosa were evaluated. RESULTS: Allergic symptom score of
      AR+NoTr was higher than the other two groups and the score of AR+Res was higher
      than the control group. Histopathologically, neither ciliary loss nor chondrocyte
      hypertrophy differed among the three groups; however, vascular congestion,
      inflammatory and plasma cell numbers, eosinophil and mast cell infiltration and
      goblet cell numbers were higher and mast cell infiltration was more prominent in
      AR+NoTr than in AR+Res and control. AR+Res and control did not differ
      significantly in any histological parameter. In AR+NoTr, nasal mucosa exhibited
      ciliary loss, squamous epithelial metaplasia, inflammatory cell infiltration,
      vascular congestion of the lamina propria and goblet cell epithelial metaplasia.
      In AR+Res, goblet cell metaplasia was focal or absent and infiltration of the
      lamina propria by inflammatory cells, eosinophils, and plasma cells was reduced
      relative to AR+NoTr. CONCLUSION: Allergic symptoms and tissue reactions were
      reduced by resveratrol treatment in rats with experimentally-induced AR.

PMID- 27040863
TI  - Validation of Carotid Artery Revascularization Coding in Ontario Health
      Administrative Databases.
AB  - PURPOSE: The positive predictive value (PPV) of carotid endarterectomy (CEA) and
      carotid artery stenting (CAS) procedure and post-operative complication coding
      were assessed in Ontario health administrative databases. METHODS: Between 1
      April 2002 and 31 March 2014, a random sample of 428 patients were identified
      using Canadian Classification of Health Intervention (CCI) procedure codes and
      Ontario Health Insurance Plan (OHIP) billing codes from administrative data. A
      blinded chart review was conducted at two high-volume vascular centers to assess
      the level of agreement between the administrative records and the corresponding
      patients' hospital charts. PPV was calculated with 95% confidence intervals (CIs)
      to estimate the validity of CEA and CAS coding, utilizing hospital charts as the
      gold standard. Sensitivity of CEA and CAS coding were also assessed by linking
      two independent databases of 540 CEA-treated patients (Ontario Stroke Registry)
      and 140 CAS-treated patients (single-center CAS database) to administrative
      records. RESULTS: PPV for CEA ranged from 99% to 100% and sensitivity ranged from
      81.5% to 89.6% using CCI and OHIP codes. A CCI code with a PPV of 87% (95% CI,
      78.8-92.9) and sensitivity of 92.9% (95% CI, 87.4-96.1) in identifying CAS was
      also identified. PPV for post-admission complication diagnosis coding was 71.4%
      (95% CI, 53.7-85.4) for stroke/transient ischemic attack, and 82.4% (95% CI, 56.6
      96.2) for myocardial infarction. CONCLUSIONS: Our analysis demonstrated that the
      codes used in administrative databases accurately identify CEA and CAS-treated
      patients. Researchers can confidently use administrative data to conduct
      population-based studies of CEA and CAS.

PMID- 27040864
TI  - Observing real-time social interaction via telecommunication methods in
      budgerigars (Melopsittacus undulatus).
AB  - Humans communicate with one another not only face-to-face but also via modern
      telecommunication methods such as television and video conferencing. We readily
      detect the difference between people actively communicating with us and people
      merely acting via a broadcasting system. We developed an animal model of this
      novel communication method seen in humans to determine whether animals also make
      this distinction. We built a system for two animals to interact via audio-visual
      equipment in real-time, to compare behavioral differences between two conditions,
      an "interactive two-way condition" and a "non-interactive (one-way) condition."
      We measured birds' responses to stimuli which appeared in these two conditions.
      We used budgerigars, which are small, gregarious birds, and found that the
      frequency of vocal interaction with other individuals did not differ between the
      two conditions. However, body synchrony between the two birds was observed more
      often in the interactive condition, suggesting budgerigars recognized the
      difference between these interactive and non-interactive conditions on some
      level. 

PMID- 27040865
TI  - Terminal-Selective Transesterification of Chlorine-Capped Poly(Methyl
      Methacrylate)s: A Modular Approach to Telechelic and Pinpoint-Functionalized
      Polymers.
AB  - Terminal-selective transesterification of chlorine-capped poly(methyl
      methacrylate)s (PMMA-Cl) with alcohols was developed as a modular approach to
      create telechelic and pinpoint-functionalized polymers. Being sterically less
      hindered and electronically activated, both the alpha-end ethyl ester and omega
      end methyl ester of PMMA-Cl were efficiently and selectively transesterified with
      diverse alcohols in the presence of a titanium alkoxide catalyst, while retaining
      the pendent esters intact, to almost quantitatively give various chlorine-capped
      telechelic PMMAs. In sharp contrast to conventional telechelic counterparts, the
      telechelic polymers obtained herein yet carry a chlorine atom at the omega
      terminal to further work as a macroinitiator in living radical polymerization.
      The iterative process of living radical polymerization and terminal-selective
      transesterification successfully afforded unique pinpoint-functionalized polymers
      where a single functional monomer unit was introduced into the desired site of
      the polymer chains. 

PMID- 27040866
TI  - Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome.
AB  - Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder
      belonging to the group of microcephalic osteodysplastic primordial dwarfisms
      (MOPD). This syndrome is characterized by short stature, skeletal anomalies,
      severe microcephaly with brain malformations and facial dysmorphism, and is
      caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small
      nuclear RNA which is a critical component of the minor spliceosome. We report
      here four foetuses and four unrelated patients with RNU4ATAC mutations. We
      provide antenatal descriptions of this rare syndrome including unusual features
      found in two twin foetuses with compound heterozygosity for two rare mutations
      who presented with mild intrauterine growth retardation and atypical dysmorphic
      facial features. We also carried out a literature review of the patients
      described up to now with RNU4ATAC mutations, affected either with TALS or Roifman
      syndrome, a recently described allelic disorder.

PMID- 27040868
TI  - CRISPR: express delivery to any DNA address.
AB  - The sudden emergence and worldwide adoption of CRISPR gene-editing technology
      confronts humanity with unprecedented opportunities and choices. CRISPR's
      transformative impact on our future understanding of biology, along with its
      potential to unleash control over the most fundamental of biological processes,
      is predictable by already achieved applications. Although its origin,
      composition, and function were revealed only recently, close to 3000 CRISPR-based
      publications have appeared including insightful and diversely focused reviews
      referenced here. Adding further to scientific and public awareness, a recent
      symposium addressed the ethical implications of interfacing CRISPR technology and
      human biology. However, the magnitude of CRISPR's rapidly emerging power mandates
      its broadest assessment. Only with the participation of a diverse and informed
      community can the most effective and humanity-positive CRISPR applications be
      defined. This brief review is aimed at those with little previous exposure to the
      CRISPR revolution. The molecules that constitute CRISPR's core components and
      their functional organization are described along with how the mechanism has been
      harnessed to edit genome structure and modulate gene function. Additionally, a
      glimpse into CRISPR's potential to unleash genetic changes with far-reaching
      consequences is presented.

PMID- 27040869
TI  - Novel PKC-zeta to p47 phox interaction is necessary for transformation from
      blebbishields.
AB  - Cancer stem cells are capable of transformation after apoptosis through the
      blebbishield emergency program. Reactive oxygen species (ROS) play an essential
      role in transformation. Understanding how ROS are linked to blebbishield-mediated
      transformation is necessary to develop efficient therapeutics that target the
      resurrection of cancer stem cells. Here we demonstrate that a novel PKC-zeta to
      p47(phox) interaction is required for ROS production in cancer cells. The
      combined use of the S6K inhibitor BI-D1870 with TNF-alpha inhibited the PKC-zeta
      to p47(phox) interaction, inhibited ROS production, degraded PKC-zeta, and
      activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870
      also inhibited transformation from cycloheximide-generated blebbishields. Thus
      ROS and the PKC-zeta to p47(phox) interaction are valid therapeutic targets to
      block transformation from blebbishields. 

PMID- 27040870
TI  - Three-Dimensional Chemical Structure Search Using the Conformational Code for
      Organic Molecules (CCOM) Program.
AB  - Searching the 3D structural fragments of organic molecules is challenging because
      of structural differences between X-ray and theoretically calculated geometries
      and the conformational flexibility of substituents. The codification program
      called Conformational Code for Organic Molecules (CCOM) can be used to
      unambiguously convert 3D conformational data for various molecules to 1D data.
      Two deviations from Rule E-5.6 of the International Union of Pure and Applied
      Chemistry (IUPAC) Rules for Nomenclature of Organic Chemistry were introduced to
      the CCOM program for 3D fragment searching. First, the search for the highest
      priority atom was limited to a distance of two bonds from the center bond for
      dihedral angle determination. Second, for indistinguishable atoms in
      experimentally observed solution structures, the smallest number of atom index in
      the molecular model was chosen as the priority atom for dihedral angle
      determination. A search of the 3D conformational fragment mb_3a6c4c of mevastatin
      () in combination with the SMiles ARbitrary Target Specification (SMARTS)
      description suggested that a change in the conformation of this fragment may be
      the driving force for dissociation of mevastatin from its target protein.
      Chirality 28:370-375, 2016. (c) 2016 Wiley Periodicals, Inc. 

PMID- 27040871
TI  - Allergic contact dermatitis caused by insect repellent wipes.

PMID- 27040872
TI  - Anogenital allergic contact dermatitis caused by methylchloroisothiazolinone,
      methylisothiazolinone and topical clotrimazole with subsequent generalized
      exanthem triggered by oral fluconazole.

PMID- 27040873
TI  - Patch testing is clinically important for patients with peri-anal dermatoses and
      pruritus ani.

PMID- 27040874
TI  - Occupational allergic contact dermatitis caused by heroin (diacetylmorphine) and
      morphine.

PMID- 27040875
TI  - Contact allergens in 'natural' hair dyes.

PMID- 27040876
TI  - Occupational contact urticaria caused by squid.

PMID- 27040877
TI  - 'Seborrhoeic dermatitis' of the head and neck without scalp involvement -
      remember nail varnish allergy.

PMID- 27040878
TI  - Friction from paper and cardboard causing occupational dermatitis in non-atopic
      individuals.

PMID- 27040879
TI  - Allergic contact dermatitis caused by the tea tree oil-containing hydrogel
      Burnshield(r).

PMID- 27040880
TI  - Resorcinol: a strong sensitizer but a rare contact allergen in the clinic.

PMID- 27040881
TI  - Photoallergic contact dermatitis caused by Quisqualis indica (Combretum indicum).

PMID- 27040882
TI  - Occupational allergic airborne contact dermatitis caused by pethoxamid - a new
      herbicide.

PMID- 27040883
TI  - Does a short patch test training course have an impact?

PMID- 27040884
TI  - WITHDRAWN: Diuretics for heart failure.

PMID- 27040885
TI  - A Case of Severe Rectal Hemorrhage Possibly Caused by Radiation Recall after
      Administration of Gemcitabine.
AB  - Radiation recall is an acute inflammatory reaction that can be triggered when
      systemic agents are administered long time after radiotherapy. Because
      radiotherapy is now indicated for many types of cancer, care should be taken
      regarding possible toxic events relating to radiotherapy in combination with
      radio-sensitizing agents. Gemcitabine, one such anti-cancer agent, is widely
      used, especially for urologic cancers. We report an intriguing case of possible
      radiation recall in the rectum caused by gemcitabine administration 37 years
      after radiation therapy. From a review of the literature, it appears that there
      have been no reported cases of radiation recall in the rectum with such a long
      interval between radiation therapy and chemotherapy. Here, we describe the case
      and provide a literature review. 

PMID- 27040886
TI  - Dynamic Role of the GTP Energy Metabolism in Cancers.
AB  - Rapid growing cells like tumor cells need a vast amount of energy to match their
      high metabolic demand. Guanine triphosphate (GTP) is one of major cellular
      metabolites and served as a building block for RNA and DNA as well as an energy
      source to drive cellular activities such as intracellular trafficking, the cell
      migration and translation. However, how cancer cells regulate GTP energy levels
      to adapt for their high demand remain largely unknown yet. In addition, how cells
      detect GTP levels remains unknown. In this seminar, I will introduce our recent
      findings that uncover dramatic change of GTP metabolism in cancer cells and a GTP
      sensing kinase that regulate metabolism for tumorigenesis.(Presented at the
      1918th Meeting, March 3, 2016). 

PMID- 27040887
TI  - The Role of the Adipocyte Hormone Leptin in Alzheimer's Disease.
AB  - Cognitive deficits are the major manifestation of Alzheimer's disease (AD);
      however, weight loss can precede the mental decline and correlates with disease
      severity. Thus, brain circuits controlling body weight may be altered early in AD
      and could be intrinsic to AD pathobiology. In mouse models, we found that amyloid
      beta, a major pathogenic factor in AD, could inhibit hypothalamic neurons in the
      leptin pathway, which was associated with early body weight/metabolic deficits.
      Ongoing research seeks to elucidate the mechanisms underlying the body
      weight/metabolic deficits and hypothalamic dysfunction in AD using both mouse
      models and clinically relevant human studies.(Presented at the 1919th Meeting,
      March 2, 2016). 

PMID- 27040888
TI  - Rhodium-catalyzed chemo- and regioselective decarboxylative addition of beta
      ketoacids to alkynes.
AB  - A highly efficient rhodium-catalyzed chemo- and regioselective addition of beta
      ketoacids to alkynes is reported. Applying a Rh(i)/(S,S)-DIOP catalyst system,
      gamma,delta-unsaturated ketones were prepared with exclusively branched
      selectivity under mild conditions. This demonstrates that readily available
      alkynes can be an alternative entry to allyl electrophiles in transition-metal
      catalyzed allylic alkylation reactions. 

PMID- 27040889
TI  - Transient Ischemic Dilatation during Stress Echocardiography: An Additional
      Marker of Significant Myocardial Ischemia.
AB  - AIM: Left ventricular (LV) transient ischemic dilatation (TID) is not clear how
      it relates to inducible myocardial ischemia during stress echocardiography (SE).
      METHODS AND RESULTS: Eighty-eight SEs were examined from the site certification
      phase of the ISCHEMIA Trial. LV end-diastolic volume (EDV) and end-systolic
      volume (ESV) were measured at rest and peak stages and the percent change
      calculated. Moderate or greater ischemia was defined as >=3 segments with stress
      induced severe hypokinesis or akinesis. Optimum cut points in stress-induced
      percent EDV and ESV change that identified moderate or greater myocardial
      ischemia were analyzed. Analysis from percentage distribution identified a > 13%
      LV volume increase in EDV or a > 9% LV volume increase in ESV as the optimum
      cutoff points for moderate or greater ischemia. Using these definitions for TID,
      there were 27 (31%) with TIDESV and 12 (14%) with TIDEDV . By logistic regression
      analysis and receiver operating characteristic curves, the percent change in ESV
      had a stronger association with moderate or greater myocardial ischemia than that
      of EDV change. Compared to those without TIDESV , cases with TIDESV had larger
      extent of inducible wall-motion abnormalities, lower peak stress LVEF, and higher
      likelihood of moderate or grater ischemia. For moderate or greater myocardial
      ischemia detection, TIDESV had a sensitivity of 46%, specificity of 83%, positive
      predictive value of 70%, and negative predictive value of 64%. CONCLUSION:
      Transient ischemic dilatation by SE is a marker of extensive myocardial ischemia
      and can be used as an additional marker of higher risk.

PMID- 27040890
TI  - Fetal Alcohol Exposure and PHACE Syndrome: A Case and Autopsy Report.
AB  - This report describes the clinical, radiologic, and autopsy findings of a newborn
      with PHACE syndrome (posterior fossa malformations, hemangioma, arterial
      anomalies, cardiac defects, and eye anomalies) and fetal alcohol spectrum
      disorder. To our knowledge, the concurrence of these conditions has not been
      reported in the literature.

PMID- 27040891
TI  - Evidence-based dentistry: assessment to document progression to proficiency.
AB  - INTRODUCTION: The integration of evidence-based dentistry (EBD) into pre-doctoral
      dental curricula requires the identification of desired outcomes, development of
      curricular content and design of assessment strategies which guide student
      performance whilst documenting achievement of desired curricular outcomes. Models
      for developing EBD curriculums have been described in the literature; however,
      the logistics of designing assessment instruments to progressively document
      student performance have received less attention. The objective of this article
      is to describe the University of Iowa's College of Dentistry's development and
      implementation of assessment strategies to guide student learning of EBD
      knowledge, application and assimilation to serve as a model for other
      institutions developing EBD assessment protocols. ASSESSMENT DEVELOPMENT: Desired
      EBD knowledge and behaviour outcomes guided the development of curricular content
      and progressive formative and summative assessment strategies. Vertically and
      horizontally integrated educational activities enabling students to demonstrate
      EBD knowledge whilst modelling desired behaviours were identified, whilst
      assessment principles guided development of learning guides and assessment
      instruments to document achievement of desired outcomes. Consistent EBD language
      and educational activities are utilised throughout the 4-year interdisciplinary
      curriculum with stepwise assessment protocols matched to the curriculum. Examples
      of student learning guides and assessment instruments are provided. SUMMARY:
      Curricular design guides development of assessment strategies. Assessment
      protocols provide consistent formative and summative feedback to enable
      continuous student growth to become proficient EBD practitioners.

PMID- 27040892
TI  - The drama of communication.

PMID- 27040893
TI  - Response and toxicity prediction by MALDI-TOF-MS serum peptide profiling in
      patients with non-small cell lung cancer.
AB  - PURPOSE: We validated a previously reported proteomic signature, associated with
      treatment outcome, in an independent cohort of patients with non-small cell lung
      cancer (NSCLC). A novel peptide signature was developed to predict toxicity.
      EXPERIMENTAL DESIGN: Using automated magnetic C18 bead-assisted serum peptide
      capture coupled to MALDI-TOF MS, we conducted serum peptide profiling of 50 NCSLC
      patients participating in a phase II trial of erlotinib and sorafenib. On the
      obtained peptide mass profiles, we applied a previously described proteomic
      classification algorithm. Additionally, associations between observed side
      effects and peptide profiles were investigated. RESULTS: Application of the
      previously acquired algorithm successfully classified the new cohort of patients
      in groups significantly associated with the outcome. The "poor" group exhibited
      shorter median progression-free survival (PFS) and overall survival (OS) of 1.35
      and 1.98 months (with p = 0.00677 and p = 0.00002, respectively) while the "good"
      group had significantly longer PFS and OS (10.63 and 14.4 months with p = 0.00142
      and p = 0.00002, respectively), compared to average OS and PFS. Two specific
      peptides were detected in the sera of all patients that developed severe
      toxicity. CONCLUSIONS AND CLINICAL RELEVANCE: Our results provide an algorithm
      that, following prospective validation in larger cohorts, could assist treatment
      selection of patients with NSCLC in the first line setting.

PMID- 27040894
TI  - Cytomorphologic findings and differential diagnosis of pulmonary papillary
      adenoma: A case report and literature review.
AB  - Pulmonary papillary adenoma is a rare tumor of the lung. Some authors refer to it
      as papillary adenoma of type II pneumocytes. It demonstrates benign behavior,
      although some references suggest that this tumor may rarely exhibit invasive
      characteristics. We report a case of pulmonary papilloma adenoma of the lung
      diagnosed by fine-needle aspiration biopsy and transbronchial biopsy. The patient
      is a 78-year-old woman, who presented to an outside facility with complaint of
      confusion after a missed episode of dialysis. On further workup, she was found to
      have a 3.8 cm irregular mass in the upper lobe of her right lung as visualized on
      chest CT. Fine-needle aspiration and a concurrent forceps-assisted transbronchial
      biopsy of the mass were performed. On microscopical examination, tumor cells
      formed small cohesive papillary fronds. On cytological evaluation, tumor cells
      were uniform medium-sized epithelial cells with moderate cytoplasm, fine
      chromatin, and inconspicuous nucleoli. The biopsies showed papillary arrangement
      of epithelial cells in a background of mild fibrosis and chronic inflammation.
      There was no piling up of cells and the nuclei were uniform with bland
      appearance. No mitoses were appreciated, and Ki-67 activity was low. The clinical
      decision was for observation. The patient suffered no complications after the
      procedures during 26 months of follow-up. We hereby present this case with a
      review of the literature. Diagn. Cytopathol. 2016;44:543-547. (c) 2016 Wiley
      Periodicals, Inc. 

PMID- 27040895
TI  - P. Prithvi Raj, MD, FIPP 1931-2016.

PMID- 27040896
TI  - Spontaneous aggregation of lithium ion coordination polymers in fluorinated
      electrolytes for high-voltage batteries.
AB  - Fluorinated carbonates are pursued as liquid electrolyte solvents for high
      voltage Li-ion batteries. Here we report aggregation of [Li(+)(FEC)3]n polymer
      species in fluoroethylene carbonate containing electrolytes and scrutinize the
      causes for this behavior. 

PMID- 27040897
TI  - Macroecology of biodiversity: disentangling local and regional effects.
AB  - Contents 404 I. 404 II. 404 III. 405 IV. 406 V. 407 VI. 408 409 References 409
      SUMMARY: Macroecology of biodiversity disentangles local and regional drivers of
      biodiversity by exploring large-scale biodiversity relationships with
      environmental or biotic gradients, generalizing local biodiversity relationships
      across regions, or comparing biodiversity patterns among species groups. A
      macroecological perspective is also important at local scales: a full
      understanding of local biodiversity drivers, including human impact, demands that
      regional processes be taken into account. This requires knowledge of which
      species could inhabit a site (the species pool), including those that are
      currently absent (dark diversity). Macroecology of biodiversity is currently
      advancing quickly owing to an unprecedented accumulation of biodiversity data,
      new sampling techniques and analytical methods, all of which better equip us to
      face current and future challenges in ecology and biodiversity conservation.

PMID- 27040898
TI  - FINE STRUCTURE AND TAXONOMY OF MONOMORPHINA AENIGMATICA COMB. NOV.
      (EUGLENOPHYTA)(1).
AB  - The euglenoid genus Monomorphina was defined by Mereschowsky in 1877 to include
      rigid euglenoids that were pyriform in lateral view, had a hyaline spine at the
      posterior end, and one to few parietal chloroplasts typically without pyrenoids.
      The genus included taxa previously assigned to Phacus Dujardin or Euglena
      Ehrenberg. The general structure of Monomorphina aenigmatica comb. nov. is
      described on the basis of light microscopy and scanning and transmission electron
      microscopy. Cells were pear-shaped in lateral view, rounded at the anterior end
      and narrowed posteriorly, tapering into a long twisted tail. The pellicle had
      helically arranged strips spiralled in a counter-clockwise fashion. A distinctive
      feature of M. aenigmatica was the presence of a single chloroplast bearing a
      pyrenoid, capped with a paramylon plate. The large parietal chloroplast extended
      along most of the cell with three prominent cup-shaped paramylon caps on the
      external face. In transverse section, the chloroplast appeared C-shaped. Because
      of the ambiguity surrounding the original descriptions used to diagnose this
      taxon, we designated an epitype for Monomorphina aenigmatica. Morphological
      features of this species were compared to other members of the genus. 

PMID- 27040899
TI  - Corrigendum for Wurzburger and Hedin (2016).

PMID- 27040900
TI  - Erratum to Araujo et al (2013).

PMID- 27040901
TI  - Reference interval of methylmalonic acid concentrations in dried blood spots of
      healthy, term newborns to facilitate neonatal screening of vitamin B12
      deficiency.
AB  - OBJECTIVES: Unrecognized vitamin B12 (B-12) deficiency in early infancy can lead
      to poor development of the child. Methylmalonic acid (MMA) is the most specific
      functional biomarker of B-12 status. To facilitate timely diagnosis and treatment
      of neonatal B-12 deficiency, the objective of this study was to calculate a
      reference interval of MMA in dried blood spots (DBSs) of healthy, term newborns.
      DESIGN AND METHODS: MMA was quantified in 160 newborn DBSs, routinely collected
      for newborn screening, using LC-MS/MS. The reference interval of DBS MMA was
      calculated according to current guidelines (CLSI EP28-A3c). The effect of storage
      at room temperature on DBS MMA concentrations was determined. RESULTS: The mean
      DBS MMA concentration of 160 healthy, term newborns was 16.8pmol (95% CI: 15.9
      17.6pmol)/8-mm spot. The reference interval (2.5th to 97.5th percentile) for MMA
      was 9.89 to 29.3pmol/8-mm spot (0.450 to 1.33MUmol/L whole blood). DBS MMA
      concentrations correlated positively (p<0.005) with storage time at room
      temperature. DBS MMA concentrations of children with methylmalonic acidemia (n=4)
      were above the upper limit of the reference interval. CONCLUSIONS: This is the
      first study to present a reference interval for DBS MMA of healthy, term newborns
      utilizing a new highly sensitive MMA method. Analysis of DBS MMA collected during
      newborn screening may have the potential to identify newborns with acquired B-12
      deficiency. Newborn DBS MMA concentrations increase with storage at room
      temperature, therefore, sample storage has to be monitored for evaluation of DBS
      MMA data.

PMID- 27040902
TI  - The evidence for clinically significant bias in plasma glucose between liquid and
      lyophilized citrate buffer additive.
AB  - OBJECTIVES: Citrate buffer additive has been suggested to be of supreme
      performance in inhibiting glycolysis. However, there is little evidence in the
      literature regarding the comparability of glucose concentrations in liquid and
      lyophilized citrate buffer containing tubes. The aim of this study was to compare
      glucose concentrations in tubes containing liquid (Glucomedics) and lyophilized
      citrate buffer (Terumo VENOSAFETM Glycemia) additive, measured immediately after
      centrifugation. DESIGN AND METHODS: Blood was collected from forty volunteers
      into both Glucomedics and Venosafe Glycemia tubes. Blood was centrifuged within
      15min from venipuncture and glucose concentration was measured immediately after
      centrifugation, on the Abbott Architect analyzer. Differences between glucose
      concentrations in Glucomedics and Terumo tubes were tested using the paired t
      test. Mean bias was calculated and compared to recommended quality specification
      for glucose (i.e. 2.2%). RESULTS: Glucose concentration in Terumo tubes was 3.4%
      lower than in Glucomedics tubes (P<0.001). The mean bias was clinically
      significant. CONCLUSIONS: There is a clinically significant difference between
      glucose concentrations in liquid and lyophilized citrate buffer additive tubes
      (Glucomedics vs. Terumo tubes) measured immediately after centrifugation. This
      difference may affect the patient outcome due to the misclassification of
      diabetes.

PMID- 27040903
TI  - Addressing value in surgical oncology: Why and how.
AB  - Value, or outcome per cost, is increasingly emphasized in the current health care
      climate. With more sophisticated and expensive therapies available, treating a
      population with growing longevity, sustainability of current trends in health
      care spending is a significant challenge. And all too often, our devices and
      therapies are implemented without understanding the value that they offer; policy
      solutions for these issues are lagging. Certainly, cancer patients, in
      particular, are at the center of these value conundrums. A majority of patients
      with malignancy are elderly, with accumulated co-morbidities, and are
      disproportionately costly. To address these contemporary issues, we must first
      identify opportunities to maximize value through improved outcomes and/or
      decreased costs. Doing so in the setting of evolving delivery and payment models
      will provide providers, health systems and insurers an opportunity to flourish
      with demonstration of high quality, low cost care. J. Surg. Oncol. 2016;114:263
      267. (c) 2016 Wiley Periodicals, Inc. 

PMID- 27040904
TI  - Bee Venom Promotes Hair Growth in Association with Inhibiting 5alpha-Reductase
      Expression.
AB  - Alopecia is an important issue that can occur in people of all ages. Recent
      studies show that bee venom can be used to treat certain diseases including
      rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we
      investigated the preventive effect of bee venom on alopecia, which was measured
      by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive
      control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors
      responsible for hair growth were analyzed by quantitative real-time PCR and
      Western blot analysis using mice skins and human dermal papilla cells (hDPCs).
      Bee venom promoted hair growth and inhibited transition from the anagen to
      catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase
      mice, hair growth was increased dose dependently compared with controls. Bee
      venom inhibited the expression of SRD5A2, which encodes a type II 5alpha
      reductase that plays a major role in the conversion of testosterone into
      dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and
      several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular
      endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee
      venom-treated hDPCs dose dependently compared with the control group. In
      conclusion, bee venom is a potentially potent 5alpha-reductase inhibitor and hair
      growth promoter. 

PMID- 27040905
TI  - Pado, a fluorescent protein with proton channel activity can optically monitor
      membrane potential, intracellular pH, and map gap junctions.
AB  - An in silico search strategy was developed to identify potential voltage-sensing
      domains (VSD) for the development of genetically encoded voltage indicators
      (GEVIs). Using a conserved charge distribution in the S2 alpha-helix, a single in
      silico search yielded most voltage-sensing proteins including voltage-gated
      potassium channels, voltage-gated calcium channels, voltage-gated sodium
      channels, voltage-gated proton channels, and voltage-sensing phosphatases from
      organisms ranging from mammals to bacteria and plants. A GEVI utilizing the VSD
      from a voltage-gated proton channel identified from that search was able to
      optically report changes in membrane potential. In addition this sensor was
      capable of manipulating the internal pH while simultaneously reporting that
      change optically since it maintains the voltage-gated proton channel activity of
      the VSD. Biophysical characterization of this GEVI, Pado, demonstrated that the
      voltage-dependent signal was distinct from the pH-dependent signal and was
      dependent on the movement of the S4 alpha-helix. Further investigation into the
      mechanism of the voltage-dependent optical signal revealed that inhibiting the
      dimerization of the fluorescent protein greatly reduced the optical signal.
      Dimerization of the FP thereby enabled the movement of the S4 alpha-helix to
      mediate a fluorescent response. 

PMID- 27040906
TI  - Techniques: Magnetic manipulation.

PMID- 27040907
TI  - The ontogeny of the cortical language network.
AB  - Language-processing functions follow heterogeneous developmental trajectories.
      The human embryo can already distinguish vowels in utero, but grammatical
      complexity is usually not fully mastered until at least 7 years of age. Examining
      the current literature, we propose that the ontogeny of the cortical language
      network can be roughly subdivided into two main developmental stages. In the
      first stage extending over the first 3 years of life, the infant rapidly acquires
      bottom-up processing capacities, which are primarily implemented bilaterally in
      the temporal cortices. In the second stage continuing into adolescence, top-down
      processes emerge gradually with the increasing functional selectivity and
      structural connectivity of the left inferior frontal cortex.

PMID- 27040908
TI  - Acquired palmoplantar keratoderma associated with hypothyroidism.

PMID- 27040909
TI  - Glucocorticoids impair oocyte developmental potential by triggering apoptosis of
      ovarian cells via activating the Fas system.
AB  - Previous studies indicate that stress damages oocytes with increased secretion of
      glucorticoids. However, although injection of female mice with cortisol decreased
      oocyte competence, exposure of mouse oocytes directly to physiological or stress
      induced concentrations of glucorticoids did not affect oocyte maturation and
      embryo development. This study has explored the mechanisms by which
      glucocorticoids impair oocyte competence. Female mice were injected with cortisol
      and the effects of cortisol-injection on oocyte competence, ovarian cell
      apoptosis and Fas/FasL activation were observed. The results showed that cortisol
      injection decreased (a) oocyte developmental potential, (b) the E2/P4 ratio in
      serum and ovaries, and (c) expression of insulin-like growth factor 1, brain
      derived neurotrophic factor and glucocorticoid receptor in mural granulosa cells
      (MGCs), while increasing levels of (a) cortisol in serum and ovaries, (b)
      apoptosis in MGCs and cumulus cells (CCs), (c) FasL secretion in ovaries and
      during oocyte maturation in vitro, and (d) Fas in MGCs, CCs and oocytes. The
      detrimental effects of cortisol-injection on oocyte competence and apoptosis of
      MGCs and CCs were significantly relieved when the gld (generalized
      lymphoproliferative disorder) mice harboring FasL mutations were observed.
      Together, the results suggested that glucocorticoids impair oocyte competence by
      triggering apoptosis of ovarian cells via activating the Fas system. 

PMID- 27040910
TI  - Development of a new in situ analysis technique applying luminescence of local
      coordination sensors: principle and application for monitoring metal-ligand
      exchange processes.
AB  - Here, we introduce the principle of the novel in situ luminescence analysis of
      coordination sensor (ILACS) approach for monitoring the formation of solid
      materials, recording information from the formed solid compounds as well as from
      the surrounding solutions. This technique utilizes as a main tool the sensitivity
      of luminescence properties of lanthanide (Ln) ions on the coordination
      environment, being incorporated as local sensors by the investigated material
      during synthesis. The luminescence spectra and their environment-dependent
      developments are monitored in situ from the early stages of the reaction until
      the final product formation under real conditions with a high time resolution.
      The ILACS principle is demonstrated here for monitoring the formation of
      [Eu(phen)2(NO3)3] (phen = 1,10-phenanthroline) and further metal-ligand exchange
      processes during its conversion to [Sn(phen)Cl4]. These reactions were followed,
      for instance, analyzing the antenna effect, shift of the (5)D0->(7)F4 Eu(3+)
      transition and quenching effects. In addition, these results have been validated
      by comparison with other in situ techniques. The results demonstrate that ILACS
      is a new powerful, fast, broadly available in situ characterization method, which
      is applicable for liquids, amorphous samples, and very small crystallites besides
      for large crystals. 

PMID- 27040911
TI  - Validity of the 12-item version of the General Health Questionnaire in detecting
      depression in the general population.
AB  - OBJECTIVES: The 12-item version of the General Health Questionnaire (GHQ-12) is
      frequently used to measure common mental disorder in public health surveys, but
      few population-based validations have been made. We validated the GHQ-12 against
      structured psychiatric interviews of depression using a population-based cohort
      in Stockholm, Sweden. METHODS: We used a population-based cohort of 484
      individuals in Stockholm, Sweden (participation rate 62%). All completed the GHQ
      12 and a semi-structured psychiatric interview. Last month DSM-III-R symptoms
      were used to classify major and minor depression. Three scoring methods for GHQ
      12 were assessed, the Standard, Likert and Corrected method. Discriminatory
      ability was assessed with area under the receiver operating characteristic (ROC)
      curve. RESULTS: A total of 9.5% had a major or minor depression. The area under
      the ROC curve was for the Standard method 0.73 (0.65-0.82), the Likert method
      0.80 (0.72-0.87) and the Corrected method 0.80 (0.73-0.87) when using major or
      minor depression as standard criterion. Adequate sensitivity and specificity for
      separating those with or without a depressive disorder was reached at >=12 Likert
      scored points (80.4 and 69.6%) or >=6 Corrected GHQ points (78.3 and 73.7%).
      Sensitivity and specificity was at >=2 Standard scored points 67.4% and 74.2%.
      CONCLUSION: When scored using the Likert and Corrected methods, the GHQ-12
      performed excellently. When scored using the Standard method, performance was
      acceptable in detecting depressive disorder in the general population. The GHQ-12
      appears to be a good proxy for depressive disorder when used in public health
      surveys.

PMID- 27040912
TI  - Knowledge and utilization of partograph among health care professionals in public
      health institutions of Bale zone, Southeast Ethiopia.
AB  - BACKGROUND: Partograph has been shown to be an efficacious tool for monitoring
      labor and identifying women in need of an obstetric intervention. Therefore, the
      aim of this study was to assess knowledge and utilization of partograph among
      health care professionals in public health institutions of Bale zone, Southeast
      Ethiopia. STUDY DESIGN: A facility-based cross-sectional study was conducted from
      February 1st to March 30, 2014. METHODS: Single population proportion sample size
      determination formula was used to calculate the sample size and it was 401.
      Simple random sampling was employed to select both the health facilities as well
      as study subjects. Data were collected using pretested structured questionnaire.
      It was analyzed by SPSS for windows version 16.0. Descriptive, binary and
      multivariable logistic regression analyses were conducted. Statistically
      significant tests were declared at a level of significance of P value <0.05.
      RESULTS: One hundred and forty (38.5%) and 224 (61.5%) study subjects have a poor
      and good level of knowledge about partograph, respectively. The magnitude of
      partograph utilization was 70.2%. Variables having statistically significant
      association with good level of knowledge about partograph were being midwives
      (AOR = 7.70, 95% CI = 2.38, 24.94), being nurses (AOR = 0.40, 95% CI = 0.19,
      0.85) and being graduated from governmental higher institution (AOR = 2.04, 95%
      CI = 1.22, 3.42). Additionally, being female health professionals (AOR = 2.39,
      95% CI = 1.17, 4.89), being hospital staff (AOR = 17.78, 95% CI = 2.32, 135.98)
      and receiving training about partograph (AOR = 2.94, 95% CI = 1.15, 7.54) have
      statistically significant association with partograph utilization. CONCLUSIONS:
      More than half of the respondents have a good level of knowledge about
      partograph. A significant number of study subjects reported use of partograph to
      monitor women in labour. It is recommended to provide periodic on-job training on
      partograph to all obstetric caregivers especially for nurses and public health
      officers to improve their knowledge.

PMID- 27040913
TI  - Country specific associations between social contact and mental health: evidence
      from civil servant studies across Great Britain, Japan and Finland.
AB  - OBJECTIVES: Little is known about which component, such as social contact of
      social networks is associated with mental health or whether such an association
      can be observed across countries. This study examined whether the association
      between frequent social contact and mental health differs by composition
      (relatives or friends) and whether the associations are similar across three
      occupational cohorts from Great Britain, Japan, and Finland. STUDY DESIGN: Cross
      sectional analysis of data from three prospective cohort studies. METHODS:
      Participants were civil servants of a prospective cohort study based in London
      (Men: n = 4519; Women: n = 1756), in the West Coast of Japan (Men: n = 2571;
      Women: n = 1102), and in Helsinki, Finland (Men: n = 1181; Women: n = 5633); we
      included the information on study variables which is complete. Mental health
      function was the study outcome, indicated by the total score from the Mental
      Health Component on the Short Form Health Survey36. Participants reported
      frequencies of contacts with their relatives or friends via a questionnaire. Age,
      marital status, and occupational position were treated as confounders in this
      study. RESULTS: Findings from multiple regression showed that the associations
      between social contact and mental health function were different depending on
      country of origin and gender. Among British or Japanese men, frequent contact
      with both friends and relatives was positively associated with their mental
      health function, while only social contact with friends was significantly
      associated with mental health of Finnish men. In women, the patterns of the
      associations between social contact and mental health were more distinctive:
      friends for Great Britain, relatives for Japan, and friends and relatives for
      Finland. These significant associations were independent of the confounders.
      CONCLUSIONS: Social contact was related to mental health of working people;
      however, culture and gender are likely to be tapped into.

PMID- 27040914
TI  - Endoplasmic reticulum stress: The cause and solution to Huntington's disease?
AB  - Accumulation of misfolded proteins is a hallmark of many human diseases,
      including several incurable neurological disorders, such as Huntington's disease
      (HD). In HD, expansion of a polyglutamine stretch within the first exon of the
      Huntingtin protein (Htt) leads to Htt misfolding, aberrant protein aggregation,
      and progressive appearance of disease symptoms. Several studies in various
      organisms (from yeast to humans) have identified the accumulation of misfolded
      secretory proteins in the endoplasmic reticulum (ER stress) as a crucial
      determinant of cellular toxicity in HD. In this review, we highlight the recent
      research linking HD to ER stress. We also discuss how the modulation of signaling
      pathways responsible for coping with misfolded protein accumulation in the ER may
      constitute attractive methods to reduce toxicity and identify new therapeutic
      targets for treatment of HD. This article is part of a Special Issue entitled
      SI:ER stress.

PMID- 27040915
TI  - How fair is my world? Development of just world beliefs among Kenyan students.
AB  - This study is a cross-sectional analysis of Kenyan adolescents' beliefs in a just
      world (BJW). Prior research suggests that BJW declines across adolescence and
      differentiate between Personal and General BJW. However, little research has been
      conducted in African samples or developing economies. Adolescents from three
      schools in Western Kenya (n = 1960) completed the questionnaires to understand
      how their Personal and General BJW differed across grades, and between schools,
      tribes, and sexes. Contrary to prior research, there was not a downward trend of
      BJW across adolescence. Instead, the trajectory was dependent upon the school and
      demographics. There were significant differences between males and females, which
      may reflect gender inequalities of the traditional Kenyan society. There were
      also significant differences between tribal groups, with those in dominant or
      majority tribes having higher perceptions of justice. This study discusses the
      role that inequality plays in adolescents' BJW and the implications for future
      cross-cultural research.

PMID- 27040917
TI  - Multi-terminal Josephson junctions as topological matter.
AB  - Topological materials and their unusual transport properties are now at the focus
      of modern experimental and theoretical research. Their topological properties
      arise from the bandstructure determined by the atomic composition of a material
      and as such are difficult to tune and naturally restricted to <=3 dimensions.
      Here we demonstrate that n-terminal Josephson junctions with conventional
      superconductors may provide novel realizations of topology in n-1 dimensions,
      which have similarities, but also marked differences with existing 2D or 3D
      topological materials. For n>=4, the Andreev subgap spectrum of the junction can
      accommodate Weyl singularities in the space of the n-1 independent
      superconducting phases, which play the role of bandstructure quasimomenta. The
      presence of these Weyl singularities enables topological transitions that are
      manifested experimentally as changes of the quantized transconductance between
      two voltage-biased leads, the quantization unit being 4e(2)/h, where e is the
      electric charge and h is the Planck constant. 

PMID- 27040916
TI  - mTORC1 and CK2 coordinate ternary and eIF4F complex assembly.
AB  - Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting
      steps in translation initiation regulated by eIF2alpha phosphorylation and the
      mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated,
      however, remains largely unknown. We show that mTOR suppresses translation of
      mRNAs activated under short-term stress wherein TC recycling is attenuated by
      eIF2alpha phosphorylation. During acute nutrient or growth factor stimulation,
      mTORC1 induces eIF2beta phosphorylation and recruitment of NCK1 to eIF2,
      decreases eIF2alpha phosphorylation and bolsters TC recycling. Accordingly,
      eIF2beta mediates the effect of mTORC1 on protein synthesis and proliferation. In
      addition, we demonstrate a formerly undocumented role for CK2 in regulation of
      translation initiation, whereby CK2 stimulates phosphorylation of eIF2beta and
      simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway.
      These findings imply a previously unrecognized mode of translation regulation,
      whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell
      proliferation. 

PMID- 27040918
TI  - Bacterial Vesicle Secretion and the Evolutionary Origin of the Eukaryotic
      Endomembrane System.
AB  - Eukaryotes possess an elaborate endomembrane system with endoplasmic reticulum,
      nucleus, Golgi, lysosomes, peroxisomes, autophagosomes, and dynamic vesicle
      traffic. Theories addressing the evolutionary origin of eukaryotic endomembranes
      have overlooked the outer membrane vesicles (OMVs) that bacteria, archaea, and
      mitochondria secrete into their surroundings. We propose that the eukaryotic
      endomembrane system originated from bacterial OMVs released by the mitochondrial
      ancestor within the cytosol of its archaeal host at eukaryote origin. Confined
      within the host's cytosol, OMVs accumulated naturally, fusing either with each
      other or with the host's plasma membrane. This matched the host's archaeal
      secretory pathway for cotranslational protein insertion with outward bound
      mitochondrial-derived vesicles consisting of bacterial lipids, forging a
      primordial, secretory endoplasmic reticulum as the cornerstone of the eukaryotic
      endomembrane system. VIDEO ABSTRACT.

PMID- 27040919
TI  - Alfalfa hay induced primary photosensitization in horses.
AB  - Photosensitization, also known as photodermatitis, occurs when phototoxic or
      photoactive substances accumulate in the skin and interact with sunlight to
      result in an often severe, crusting, itching or painful dermatitis in unpigmented
      and/or lightly haired areas of the skin. Primary photosensitization, caused by
      direct ingestion of photosensitizing agents, has been reported anecdotally in
      horses after ingestion of alfalfa hay. Between 2004 and 2014, several large
      outbreaks of primary photosensitization in horses fed primarily alfalfa hay were
      investigated in California. Alfalfa hay samples were collected and carefully
      examined for the presence of known photosensitizing plants and pesticide residues
      but none were identified. Select hay samples were evaluated for unusual fungal
      infestation and for phototoxicity assay using a specific Candida albicans assay;
      results were negative. In the 2004 outbreak, a feeding study was conducted with
      three horses exclusively fed alfalfa hay that was suspected to have caused the
      outbreak. Two weeks after ingestion of alfalfa hay, two horses developed several
      lesions in non-pigmented skin characterized as chronic ulcerative and necrotizing
      dermatitis with superficial vasculitis, which was consistent with
      photosensitization. In the 2014 outbreak, seven different implicated alfalfa hay
      samples were analyzed for chlorophyll a and b, and pheophorbide a. These
      compounds had been suspected to play a role in alfalfa-induced primary
      photosensitization. The chlorophyll contents ranged from 0.90 to 2.30 mg/g in the
      alfalfa hay samples, compared to 1.37 and 2.94 mg/g in locally grown alfalfa and
      orchard grass hay. The pheophorbide a levels ranged from 3.36 to 89.87 ug/g in
      alfalfa samples compared to 81.39 and 42.33 ug/g in control alfalfa and orchard
      grass hay samples. These findings eliminate chlorophyll a, chlorophyll b, and
      pheophorbide a as possible causes for alfalfa-hay induced primary
      photosensitization. 

PMID- 27040920
TI  - Behavioural change by pig producers is the key factor in raising pigs with intact
      tails.

PMID- 27040921
TI  - The relationship between terminal QRS distortion on initial ECG and final infarct
      size at 4months in conventional ST- segment elevation myocardial infarct
      patients.
AB  - BACKGROUND: In the Sclarovsky-Birnbaum Ischemia Severity Grading System for
      patients with ST-segment elevation myocardial infarction (STEMI), "Terminal QRS
      distortion" is considered as "Grade III". This evidence for most severe ischemia
      is associated with cardiovascular magnetic resonance imaging (CMR) markers of
      myocardial damage in the subacute phase. Our aim was to assess whether terminal
      QRS distortions on the initial electrocardiogram (ECG) is predictive for infarct
      size (IS) and left ventricular ejection fraction (LVEF) at 4months in anterior
      versus infarct locations. METHODS: Patient data of the HEBE, GIPS III and MAST,
      were pooled. ECGs of 411 STEMI patients were classified as absence (Grade II) or
      presence (Grade III) of terminal QRS distortion according to Sclarovsky-Birnbaum
      grading. CMR was performed at approximately 4months and included IS and LVEF.
      RESULTS: Grade III ischemia was present in 142 of 411 (35%) patients and was more
      frequently observed with inferior STEMI (P=0.01). In the total cohort and in
      anterior STEMI, no difference in LVEF or IS was observed between the two Grades.
      Whereas, in inferior STEMI Grade III was associated with a larger IS (P<0.01) and
      also, a trend towards a lower LVEF was observed (P=0.09). CONCLUSION: In inferior
      STEMI, terminal QRS distortion on the initial ECG is associated with a larger IS
      at approximately 4months, and can be used to identify a high-risk population in
      the acute phase. Also, a Grade III was associated with a trend towards a lower
      LVEF.

PMID- 27040922
TI  - Chronic stress and Rosiglitazone increase indices of vascular stiffness in male
      rats.
AB  - Prolonged and/or frequent exposure to psychological stress responses may lead to
      deterioration of organs and tissues, predisposing to disease. In agreement with
      this, chronic psychosocial stress is linked to greater cardiovascular risk,
      including increased incidence of atherosclerosis, myocardial ischemia, coronary
      heart disease, and death. Thus the association between stress and cardiovascular
      dysfunction represents an important node for therapeutic intervention in
      cardiovascular disease. Here we report that 2weeks of chronic variable stress
      (CVS) increased indices of vascular stiffness, including increased collagen
      deposition in the aortic adventitia and increased resting pulse pressure, in male
      rats. Thus CVS may represent a useful rodent model for stress-associated CVD,
      especially for aging populations for which widening pulse pressure is a well
      known risk factor. Additionally, we report that the thiazolidinedione
      Rosiglitazone (RSG) blunts chronic stress-associated increases in circulating
      corticosterone. Despite this, RSG was not protective against adverse
      cardiovascular outcomes associated with chronic stress. Rather RSG itself is
      associated with increased pulse pressure, and this is exacerbated by chronic
      stress-highlighting that chronic stress may represent an additional contributor
      to RSG-associated cardiovascular risk.

PMID- 27040923
TI  - Lipophyllodes of the breast. A reappraisal of fat-rich tumors of the breast based
      on 22 cases integrated by immunohistochemical study, molecular pathology
      insights, and clinical follow-up.
AB  - We have studied 22 cases of mammary lipophyllodes tumors (LPT), analyzing their
      clinicopathologic features along with available follow-up. All cases were tested
      for cytokeratins, S100 protein, and MDM2, and in selected cases for estrogen
      receptor, smooth muscle actin, bcl2, desmin, and myogenin. Patients were women
      aged 21 to 69 years (average, 45 years), and LPT size ranged from 1.6 to 30 cm
      (average, 9.7 cm). Microscopically, LPT segregated as follows: atypical lipoma
      like tumor/well-differentiated liposarcoma (ALT/WDL), 8 cases; myxoid, 6; and
      pleomorphic/poorly differentiated/round cell, 8, including a case of
      dedifferentiated liposarcoma. Immunohistochemistry studies showed focal positive
      staining for S100 and CD34 in most ALT/WDL, and desmin and myogenin in 2 cases
      with evidence of rhabdomyoblastic differentiation. MDM2 positivity was focally
      seen in 1 case. Follow-up was available in 8 cases. Multiple recurrent tumors
      were seen in 2 patients, and metastatic disease to the lung was seen in 2
      patients. In 4 patients with a follow-up between 2 and 15 years there was no
      evidence of recurrent or metastatic disease. Patients with ALT/WDL (2/2) were
      alive with no evidence of disease; 2 of 4 patients with myxoid liposarcoma
      component experienced tumor recurrence, whereas pleomorphic liposarcoma LPT
      pursued a less favorable course although only 1 patient died of the condition.
      Absence of MDM2 reactivity in most cases seems not as meaningful as in fatty
      tumors of somatic soft parts. 

PMID- 27040924
TI  - Recurrent TERT promoter mutations in urothelial carcinoma and potential clinical
      applications.
AB  - Increased telomerase activity is associated with almost all types of advanced
      human cancers with unknown molecular mechanism(s). Two recurrent point mutations
      in the promoter region of telomerase reverse transcriptase (TERT)--the key
      subunit of telomerase--have recently been identified in melanoma as well as a
      small sample of bladder cancer cell lines. However, the incidence and clinical
      pathological significance of these mutations in urothelial carcinoma have not
      been well established yet. We collected 86 specimens of urothelial carcinoma
      including upper and lower urinary tract: high grade and low grade, invasive and
      noninvasive, and primary and metastatic. We also included some matched benign
      urothelium and common benign bladder lesions: cystitis, nephrogenic adenoma, and
      inverted papilloma. In addition, we collected urine samples for urothelial
      carcinoma workup; blood samples from patients underwent cystectomy with extensive
      lymphovascular invasion. All specimens were subject to polymerase chain reaction
      amplification and bidirectional Sanger sequencing for the TERT promoter
      mutations: C228T and C250T. We found that 64 (74%) of 86 carcinoma samples
      harbored 1 of the 2 TERT promoter mutations (C228T, n = 54; C250T, n = 10); the
      incidences were roughly equal regardless of site of origin, histologic grade, and
      invasive status. All matched benign and benign lesion samples showed wild-type
      sequence. These TERT promoter mutations are the most common genetic alterations
      in urothelial carcinoma and are not associated with tumor locations, grade, or
      invasiveness. Importantly, the feasibility of detecting these mutations in urine
      samples may provide a novel method to detect urothelial carcinoma in urine.

PMID- 27040925
TI  - Anatomic pathology in Cuba before 1959: a personal recollection.
AB  - Reminiscing when reaching life's twilight is a human condition and hopefully
      leads to an objective self-evaluation of the past years. I have just done that
      with this recollection and now I can conclude that, in spite of the outcome of my
      professional life in Cuba, I remain convinced that one should not complete a
      journey just because it was started, that everything we learn in life will be
      sued in due time, and that we should always pursue our dreams because we become
      our best in the process. 

PMID- 27040926
TI  - Angiosarcoma arising in association with vascular Dacron grafts and orthopedic
      joint prostheses: clinicopathologic, immunohistochemical, and molecular study.
AB  - Angiosarcoma may rarely arise near an inert foreign body material including
      vascular grafts and metal joint prostheses. Sixteen such cases have been reported
      since 1972 but mostly in the radiologic or surgical literature without detailed
      histologic or molecular analyses. We herein describe the clinicopathologic and
      molecular features of 2 new cases and reanalyzed 3 previously reported cases of
      angiosarcoma that developed in association with Dacron grafts for vascular repair
      (n=3) or related to orthopedic metal prostheses for joint replacement (n=2). All
      patients were men aged 50 to 84 years (median, 71 years). Mean time to
      development of angiosarcoma was 9 years (range, 4.6-17 years). Symptoms were
      recurrent bleeding/loosening of prosthesis for suspected infection (in the joint
      prosthesis cases) and fatigue, weight loss, and abdominal symptoms in the Dacron
      associated cases. Four patients died of disease within 1 to 24 months (mean, 8
      months). One patient was alive after radical surgery, radiochemotherapy, and
      embolization of pulmonary metastases (17 months). Histologically, all tumors were
      high-grade epithelioid neoplasms with a predominant solid growth pattern and
      variable vasoformation. All tumors expressed CD31, ERG, FLI-1, and variably
      pancytokeratin (diffuse in 3 cases), but none expressed D2-40, MDM2, or CDK4.
      Fluorescence in situ hybridization analysis revealed no MDM2 or CDK4 alterations.
      MYC was expressed in all cases, but only 1 case was MYC amplified by fluorescence
      in situ hybridization. Angiosarcomas are exceedingly rare fatal complications of
      long-standing metal and Dacron prostheses. Awareness of their morphology and
      frequent cytokeratin expression is necessary to avoid misdiagnosis as metastatic
      carcinoma. Limited awareness of their existence explains delayed clinical
      diagnosis in most of cases. Absence of MDM2/CDK4 alterations underlines their
      distinction from intimal-type sarcomas.

PMID- 27040927
TI  - p53 expression and relationship with MDM2 amplification in breast carcinomas.
AB  - Carcinoma of the breast, like other malignancies, is a genetic disease with
      multiple genetic events leading to the malignant phenotype. p53 mutations are the
      most common genetic events in human cancer. Inactivation of p53 can be a result
      of mutation in gene sequence. One of the main structures that regulate p53
      stabilization is MDM2. It suppresses p53 transcriptional activation by
      recognizing transactivation domain of p53. The loss of MDM2 function on p53
      regulation results in deprivation of p53 tumor suppressor ability. Single
      nucleotide polymorphisms (SNP309 T->G exchange) or MDM2 amplification has been
      proposed to play a role in this issue. In the present study, our aim is to
      analyze p53 and MDM2 status and investigate their interactions in human sporadic
      breast carcinoma. The study groups were separated according to their molecular
      classifications. In each group, histologic type of the tumor, conventional
      prognostic parameters, p53, and MDM2 interactions were compared statistically.
      Tumors are divided into 4 subtypes due to estrogen and progesterone receptor
      status, HER-2, and Ki-67 proliferation index results. According to this
      classification, 23 cases are in the luminal A, 32 cases are in the luminal B, 15
      cases are in the HER-2 positive, and 22 cases are in the triple-negative group,
      with a total of 92 cases. p53 expression is low in luminal breast carcinomas than
      HER-2 and triple-negative subtypes. MDM2 amplification frequency was found to be
      5.4% in total. MDM2 gene amplification does not have a significant role in breast
      carcinogenesis, but other possible mechanisms may play a role in its
      inactivation. 

PMID- 27040928
TI  - Surgical excision outcome after radial scar without atypical proliferative lesion
      on breast core needle biopsy: a single institutional analysis.
AB  - Radial scar (RS) has been recognized as a risk factor for developing breast
      cancer, and excision is recommended for patients with RS identified on core
      needle biopsy (CNB). However, recent literatures suggest that the increased risk
      may be caused by concurrent proliferative lesions on the biopsy, rather than
      radial scar itself. In this study, we investigated the follow-up excision (FUE)
      results for patients with RS on CNB with no history of a prior or a concurrent
      breast cancer or atypical proliferative lesions (APLs). A total of 113 RS cases
      including 32 cases with APLs or carcinoma and 81 cases without APLs on CNB were
      included in this study. Forty cases (49%) without APLs had FUE. No significant
      difference in radiologic and clinical findings was identified between cases with
      FUEs and cases without FUEs. Of the 40 cases with FUE, 9 cases (22.5%) were
      upgraded including 3 atypical ductal hyperplasias, 4 lobular neoplasias, 1 flat
      epithelial atypia, and 1 atypical apocrine adenosis. However, no case was
      upgraded to invasive carcinoma or ductal carcinoma in situ. All cases with
      mammotome CNBs were not upgraded. Our data suggest that conservative follow-up
      with imaging rather than surgical excisions may be more appropriate for patients
      with only RS on biopsy, especially for patients with mammotome CNBs. 

PMID- 27040929
TI  - Osteoclast-rich, proximal-type epithelioid sarcoma: clinicopathologic features of
      3 unusual cases expanding the histomorphological spectrum.
AB  - Epithelioid sarcoma (ES) displays a wide clinicopathologic spectrum. On
      histopathology, osteoclast-like giant cells have been rarely described in these
      tumors. A 45-year-old gentleman presented with a perineal swelling of 6-month
      duration. Radiologic imaging disclosed a large, highly vascular tumor mass in his
      perineal region that was diagnosed elsewhere as pigmented villonodular synovitis.
      A 58-year-old lady presented with a recurrent tumor in her right inguinolabial
      region for which she underwent multiple tumor resections in the past. A 33-year
      old lady presented with a right inguinal swelling of 1-month duration that was
      diagnosed elsewhere as a non-Hodgkin lymphoma on fine needle aspiration cytology.
      Histopathologic examination of tumors in all the 3 cases revealed epithelioid to
      "rhabdoid-like" cells arranged in a diffuse pattern interspersed with many
      osteoclast-like giant cells. The first tumor also revealed focal
      pseudoangiosarcomatous areas and heterotopic bone formation. By
      immunohistochemistry, tumor cells in all 3 cases were positive for AE1/AE3,
      epithelial membrane antigen, and CD34 and were completely negative for
      INI1/SMARCB1. CD68 immunostaining in 2 tumors highlighted osteoclast-like giant
      cells. Osteoclast-rich, proximal-type ES are unusual tumors, indicative of an
      expanding spectrum of ESs. Awareness of this histopathologic pattern and
      diagnostic confirmation with necessary immunohistochemical stains is crucial to
      avoid misinterpretation, as these tumors are clinically aggressive and are
      treated with wide local excision and optional adjuvant radiation therapy. 

PMID- 27040930
TI  - Histopathological review of 667 cases of oral mucoceles with emphasis on uncommon
      histopathological variations.
AB  - Mucoceles can occur in the oral cavity, appendix, bladder, paranasal sinuses, and
      lacrimal sac. In the oral cavity, mucoceles arise from pathological alterations
      in the minor salivary gland ducts. In this study, we aimed to histologically
      reevaluate cases of oral mucoceles to identify possible variants. A total of 667
      slides containing tissue sections stained with hematoxylin and eosin diagnosed as
      a phenomenon of mucus extravasation were analyzed under light microscopy by 4
      previously trained examiners. In 128 cases (19.1%), 1 or more histopathological
      changes were identified. Twenty cases (2.9%) exhibited collagenous globular
      structures compatible with myxoglobulosis. In 30 cases (4.49%), dissociation of
      collagen fibers after mucin extravasation was observed. Fifty-four cases (8.09%)
      exhibited papillary synovial metaplasia-like change, and 32 (4.79%) showed a
      significant reduction in the lumen of the cavity due to large papillae. Twenty
      cases (2.9%) were compatible with superficial mucoceles, and in 11 cases (1.64%),
      the foamy macrophages showed an unusual solid arrangement, known as clear cell
      change. It is essential to recognize the possible histopathological changes in
      oral mucoceles to avoid diagnostic pitfalls. 

PMID- 27040931
TI  - Comparison of margin status and lesional size between radioactive seed localized
      vs conventional wire localized breast lumpectomy specimens.
AB  - Despite the known benefits of the use of radioactive seed localization (RSL), few
      studies have looked at the resultant pathologic marginal status of these
      lumpectomy specimens, especially in regard to different definitions of
      close/positive margins. We compared the marginal status of lumpectomy specimens
      removed by either RSL or conventional wire localization (CWL) techniques. A total
      of 106 lumpectomy specimens including 62 by CWL and 44 by RSL for invasive ductal
      and lobular carcinomas were compared. Data on gross and microscopic surgical
      margin status, tumor type and grade, and demographic information were
      retrospectively collected. There was no difference between the techniques in
      terms of tumor characteristics including size, histologic grade, lymph node
      positivity, or age. Although the distributions are very similar between CWL and
      RSL specimens for final marginal assessments (P=.69), there is a (modest)
      statistically significant difference in the distribution for margin
      classifications based on gross assessments (P=.040), specifically more RSL
      specimens exhibiting tumor within 1mm of the closest margin. Concordance between
      gross and microscopic lesion measurements is highest for invasive ductal
      carcinoma grade 3 for both CWL and RSL lumpectomies (78.6% and 80.0%). This study
      shows that there were no significant marginal status differences between RSL and
      CWL lumpectomy specimens with invasive carcinoma. Rather, what was relevant is
      whether the entire specimen could be classified as having negative/close margins.
      Significant workflow challenges in surgical pathology laboratories are expected
      with the adoption of the RSL process. 

PMID- 27040932
TI  - Preleukemic phase of chronic myelogenous leukemia: morphologic and
      immunohistochemical characterization of 7 cases.
AB  - Patients with chronic myelogenous leukemia (CML) present typically with an
      elevated white blood cell count (WBC) and cytogenetic or molecular genetic
      evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a
      normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in
      this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to
      73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected
      by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the
      diagnosis of preleukemic CML (pre-CML). We compared these patients with a group
      of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a
      leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed
      on all bone marrow biopsy specimens. Peripheral blood absolute basophilia
      (>=200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in
      all CML-CP cases and absent in leukemoid reaction cases. The mean +/-SD of
      microvascular density of pre-CML cases (10.0 +/- 4.3 vessels/200* field) was
      twice that of leukemoid reaction cases (5.0 +/- 1.0) (P=.02; Student t test) but
      similar to that of CML-CP cases (12.5 +/- 3.6). Microvessels in pre-CML,
      highlighted by CD34, were tortuous with abnormal branching, although to a lesser
      extent than those found in CML-CP. Microvessels in leukemoid reaction were
      generally straight. The percentage of small, hypolobated megakaryocytes,
      highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction
      cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML
      should be suspected in patients with a normal to mildly elevated WBC and absolute
      basophilia. Bone marrow examination can usually distinguish pre-CML from a
      leukemoid reaction based on the percentage of small, hypolobated megakaryocytes;
      microvascular density; and morphologic features.

PMID- 27040933
TI  - Dietary beta-carotene and lutein metabolism is modulated by the APOE genotype.
AB  - The human apolipoprotein E (APOE) genotype has been suggested to interact with
      nutrient metabolism particularly with lipid soluble vitamins. Plasma carotenoid
      levels are determined by numerous dietary and genetic factors with high inter
      individual variation; however, the APOE genotype has not been systematically
      examined so far. Our aim was to investigate the effect of the APOE genotype on
      dietary carotenoid metabolism with special regard to transcriptional regulation
      of carotenoid absorption, cleavage and adipocyte fat storage. We supplemented
      targeted replacement mice expressing human APOE3 and APOE4 isoforms with dietary
      beta-carotene (BC) and lutein (LUT) for 8 weeks. Plasma BC and adipose tissue BC
      and LUT levels were in trend lower in APOE4 than APOE3 mice, while hepatic
      expression of the beta-carotene oxygenases BCO1 and BCO2 was significantly
      higher. In contrast to the liver, mRNA levels of proteins involved in carotenoid
      absorption and cleavage in the small intestinal mucosa as well as of adipogenic
      markers in the adipose tissue were not different between APOE3 and APOE4 mice.
      Our data suggest that the hepatic carotenoid cleavage activity is higher in APOE4
      mice partially reducing the circulation and extra-hepatic accumulation of intact
      carotenoids as compared to APOE3. Therefore we suggest considering the APOE
      genotype as modulator of carotenoid status in the future. (c) 2016 BioFactors,
      42(4):388-396, 2016. 

PMID- 27040934
TI  - Altitude training for elite endurance athletes: A review for the travel medicine
      practitioner.
AB  - High altitude training is regarded as an integral component of modern athletic
      preparation, especially for endurance sports such as middle and long distance
      running. It has rapidly achieved popularity among elite endurance athletes and
      their coaches. Increased hypoxic stress at altitude facilitates key physiological
      adaptations within the athlete, which in turn may lead to improvements in sea
      level athletic performance. Despite much research in this area to date, the exact
      mechanisms which underlie such improvements remain to be fully elucidated. This
      review describes the current understanding of physiological adaptation to high
      altitude training and its implications for athletic performance. It also
      discusses the rationale and main effects of different training models currently
      employed to maximise performance. Athletes who travel to altitude for training
      purposes are at risk of suffering the detrimental effects of altitude. Altitude
      illness, weight loss, immune suppression and sleep disturbance may serve to limit
      athletic performance. This review provides an overview of potential problems
      which an athlete may experience at altitude, and offers specific training
      recommendations so that these detrimental effects are minimised. 

PMID- 27040935
TI  - Bilateral pleural effusion in a HIV negative patient - TB or not TB?
AB  - Pleural tuberculosis is an infrequent cause of respiratory illness in Europe and
      usually presents unilaterally. We present the case of a young, immunocompetent
      sailor from the Phillippines, who presented with bilateral pleural fluid caused
      by Mycobacterium tuberculosis infection in the Netherlands. In addition
      challenges in the diagnostic process are discussed. 

PMID- 27040936
TI  - Hybridizing cross-polarization with NOE or refocused-INEPT enhances the
      sensitivity of MAS NMR spectroscopy.
AB  - Heteronuclear cross polarization (CP) has been commonly used to enhance the
      sensitivity of dilute low-gamma nuclei in almost all solid-state NMR experiments.
      However, CP relies on heteronuclear dipolar couplings, and therefore the
      magnetization transfer efficiency becomes inefficient when the dipolar couplings
      are weak, as is often the case for mobile components in solids. Here, we
      demonstrate methods that combine CP with heteronuclear Overhauser effect
      (referred to as CP-NOE) or with refocused-INEPT (referred to as CP-RINEPT) to
      overcome the efficiency limitation of CP and enhance the signal-to-noise ratio
      (S/N) for mobile components. Our experimental results reveal that, compared to
      the conventional CP, significant S/N ratio enhancement can be achieved for
      resonances originating from mobile components, whereas the resonance signals
      associated with rigid groups are not significantly affected due to their long
      spin-lattice relaxation times. In fact, the S/N enhancement factor is also
      dependent on the temperature, CP contact time as well as on the system under
      investigation. Furthermore, we also demonstrate that CP-RINEPT experiment can be
      successfully employed to independently detect mobile and rigid signals in a
      single experiment without affecting the data collection time. However, the
      resolution of CP spectrum obtained from the CP-RINEPT experiment could be
      slightly compromised by the mandatory use of continuous wave (CW) decoupling
      during the acquisition of signals from rigid components. In addition, CP-RINEPT
      experiment can be used for spectral editing utilizing the difference in dynamics
      of different regions of a molecule and/or different components present in the
      sample, and could also be useful for the assignment of resonances from mobile
      components in poorly resolved spectra. Therefore, we believe that the proposed
      approaches are beneficial for the structural characterization of multiphase and
      heterogeneous systems, and could be used as a building block in multidimensional
      solid-state NMR experiments.

PMID- 27040938
TI  - Sensitive surface plasmon resonance enabled by templated periodic arrays of gold
      nanodonuts.
AB  - Here we report a simple and scalable colloidal lithography technology for
      fabricating periodic arrays of gold nanodonuts for sensitive surface plasmon
      resonance (SPR) analysis. This new bottom-up approach leverages a unique polymer
      wetting layer between a self-assembled, non-close-packed monolayer silica
      colloidal crystal and a silicon substrate to template ordered gold nanodonuts
      with tunable geometries over wafer-sized areas. The processes involved in this
      templating nanofabrication approach, including spin coating, oxygen plasma
      etching, and metal sputtering, are all compatible with standard microfabrication
      technologies. Specular reflection measurements reveal that the efficient
      electromagnetic coupling of the incident light with the tunable SPR modes of the
      templated gold nanodonut arrays enables good spectral tunability. Bulk refractive
      index sensing experiments show that a high SPR sensitivity of ~758 nm per
      refractive index unit, which outperforms many plasmonic nanostructures fabricated
      by both top-down and bottom-up approaches, can be achieved using the templated
      gold nanodonut arrays. Numerical finite-difference time-domain simulations have
      also been performed to complement the optical characterization and the
      theoretical results match well with the experimental measurements. 

PMID- 27040937
TI  - Safety and Efficacy of Minimally Invasive Acetabular Stabilization for
      Periacetabular Metastatic Disease with Thermal Ablation and Augmented Screw
      Fixation.
AB  - PURPOSE: To evaluate minimally invasive acetabular stabilization (MIAS) with
      thermal ablation and augmented screw fixation for impending or minimally
      displaced fractures of the acetabulum secondary to metastatic disease. MATERIALS
      AND METHODS: Between February 2011 and July 2014, 13 consecutive patients
      underwent thermal ablation, percutaneous screw fixation, and polymethyl
      methacrylate augmentation for impending or nondisplaced fractures of the
      acetabulum secondary to metastatic disease. Functional outcomes were evaluated
      before and after the procedure using the Musculoskeletal Tumor Society (MSTS)
      scoring system. Complications, hospital length of stay, and eligibility for
      chemotherapy and radiation therapy were assessed. RESULTS: All procedures were
      technically successful with no major periprocedural complications. The mean total
      MSTS score improved from 23% +/- 11 before MIAS to 51% +/- 21 after MIAS (P <
      .05). The mean MSTS pain scores improved from 0% (all) to 32% +/- 22 after MIAS
      (P < .05). The mean MSTS walking ability score improved from 22% +/- 19 to 55% +/
      26 after MIAS (P < .05). Two complications occurred; a patient had a minimally
      displaced fracture of the superior pubic ramus at the site of repair but remained
      ambulatory, and septic arthritis was diagnosed in another patient 12 months after
      repair. The average length of hospital stay was 2 days +/- 3.6; six patients were
      discharged within 24 hours of the procedure. All patients were eligible for
      chemotherapy and radiation therapy immediately after the procedure. CONCLUSIONS:
      MIAS is feasible, improves pain and mobility, and offers a minimally invasive
      alternative to open surgical reconstruction.

PMID- 27040939
TI  - Commentary: From the primacy of safe passage for refugees to a global social
      policy.

PMID- 27040940
TI  - Identification of transglutaminase 2 kinase substrates using a novel on-chip
      activity assay.
AB  - Transglutaminase 2 (TG2) is an enzyme that plays a critical role in a wide
      variety of cellular processes through its multifunctional activities. TG2 kinase
      has emerged as an important regulator of apoptosis, as well as of chromatin
      structure and function. However, systematic investigation of TG2 kinase
      substrates is limited due to a lack of a suitable TG2 kinase activity assays.
      Thus, we developed a novel on-chip TG2 kinase activity assay for quantitative
      determination of TG2 kinase activity and for screening TG2 kinase substrate
      proteins in a high-throughput manner. Quantitative TG2 kinase activity was
      determined by selective detection of substrate protein phosphorylation on the
      surface of well-type amine arrays. The limit of detection (LOD) of this assay was
      4.34MUg/ml. We successfully applied this new activity assay to the kinetic
      analysis of 27 TG2-related proteins for TG2 kinase activity in a high-throughput
      manner and determined Michaelis-Menten constants (Km) of these proteins. We used
      the Km values and cellular locations of the TG2-related proteins to construct a
      substrate affinity map for TG2 kinase. Therefore, this on-chip TG2 kinase
      activity assay has a strong potential for the systematic investigation of
      substrate proteins and will be helpful for studying new physiological functions. 

PMID- 27040941
TI  - Highly sensitive homogeneous electrochemical aptasensor for antibiotic residues
      detection based on dual recycling amplification strategy.
AB  - The ubiquitous presence of antibiotic residues in foodstuff have serious health
      consequences for consumers from allergic reactions to the evolution of antibiotic
      resistant bacteria. To address this problem, a novel homogeneous electrochemical
      aptasensor with high sensitivity and specificity is designed for antibiotic
      residues detection based on target-induced and T7 exonuclease-assisted dual
      recycling signal amplification strategy. It was realized by the remarkable
      diffusivity difference between hairpin probe and the mononucleotides towards the
      negatively charged indium tin oxide electrode. For the proof-of-concept
      experiment, ampicillin, was employed as a model analyte to examine the desirable
      properties of this assay. A low detection limit of 4.0pM toward ampicillin with
      an excellent selectivity could be achieved, which has been successfully applied
      to assay antibiotic in milk. What's more, compared with the immobilization-based
      electrochemical means, the proposed sensing system avoids the tedious and time
      consuming steps of electrode modification, making the experimental processes much
      simpler and more convenient. With the advantages of high sensitivity, excellent
      selectivity and simple operation, it is believed that this strategy possesses
      great potential for the simple, easy and convenient detection of antibiotic
      residues in food safety field. 

PMID- 27040942
TI  - Electrokinetic effect for molecular recognition: A label-free approach for real
      time biosensing.
AB  - We present a simple and inexpensive method for label-free detection of
      biomolecules. The method monitors the changes in streaming current in a fused
      silica capillary as target biomolecules bind to immobilized receptors on the
      inner surface of the capillary. To validate the concept, we show detection and
      time response of different protein-ligand and protein-protein systems: biotin
      avidin and biotin-streptavidin, barstar-dibarnase and Z domain-immunoglobulin G
      (IgG). We show that specific binding of these biomolecules can be reliably
      monitored using a very simple setup. Using sequential injections of various
      proteins at a diverse concentration range and as well as diluted human serum we
      further investigate the capacity of the proposed technique to perform specific
      target detection from a complex sample. We also investigate the time for the
      signal to reach equilibrium and its dependence on analyte concentration and
      demonstrate that the current setup can be used to detect biomolecules at a
      concentration as low as 100pM without requiring any advanced device fabrication
      procedures. Finally, an analytical model based on diffusion theory has been
      presented to explain the dependence of the saturation time on the analyte
      concentration and capillary dimensions and how reducing length and inner diameter
      of the capillary is predicted to give faster detection and in practice also lower
      limit of detection. 

PMID- 27040943
TI  - Early detection of skin cancer via terahertz spectral profiling and 3D imaging.
AB  - Terahertz scanning reflectometry, terahertz 3D imaging and terahertz time-domain
      spectroscopy have been used to identify features in human skin biopsy samples
      diagnosed for basal cell carcinoma (BCC) and compared with healthy skin samples.
      It was found from the 3D images that the healthy skin samples exhibit regular
      cellular pattern while the BCC skin samples indicate lack of regular cell
      pattern. The skin is a highly layered structure organ; this is evident from the
      thickness profile via a scan through the thickness of the healthy skin samples,
      where, the reflected intensity of the terahertz beam exhibits fluctuations
      originating from different skin layers. Compared to the healthy skin samples, the
      BCC samples' profiles exhibit significantly diminished layer definition; thus
      indicating a lack of cellular order. In addition, terahertz time-domain
      spectroscopy reveals significant and quantifiable differences between the healthy
      and BCC skin samples. Thus, a combination of three different terahertz techniques
      constitutes a conclusive route for detecting the BCC condition on a cellular
      level compared to the healthy skin. 

PMID- 27040944
TI  - An electrochemical immunosensor for efficient detection of uropathogenic E. coli
      based on thionine dye immobilized chitosan/functionalized-MWCNT modified
      electrode.
AB  - Uropathogenic Escherichia coli (UPEC) is the major cause of 150 million Urinary
      Tract Infections (UTI) reported annually world-wide. High prevalence of multi
      drug-resistance makes it dangerous and difficult to cure. Therefore simple, quick
      and early diagnostic tools are essential for effective treatment and control. We
      report an electrochemical immunosensor based on thionine dye (Th) immobilized on
      functionalized-multiwalled carbon nanotube+chitosan composite coated on glassy
      carbon electrode (GCE/f-MWCNT-Chit@Th) for quick and sensitive detection of UPEC
      in aqueous solution. This immunosensor was constructed by sequential
      immobilization of UPEC, bovine serum albumin, primary antibody and Horse Radish
      Peroxidase (HRP) tagged secondary antibody on the surface of GCE/f-MWCNT-Chit@Th.
      When analyzed using 2.5mM of hydrogen peroxide reduction reaction using cyclic
      voltammetry in phosphate buffer, pH 7.0, the immunosensor showed excellent
      linearity in a range of 10(2)-10(9)cfu of UPEC mL(-1) with a current sensitivity
      of 7.162MUA {log(cfumL(-1))}(-1). The specificity of this immunosensor was tested
      using other UTI and non-UTI bacteria, Staphylococcus, Klebsiella, Proteus and
      Shigella. The clinical applicability of the immunosensor was also successfully
      tested directly in UPEC spiked urine samples (simulated sample). 

PMID- 27040945
TI  - Effect of PI3K/Akt Signaling Pathway on the Process of Prostate Cancer Metastasis
      to Bone.
AB  - We sought to study the effects of PI3K/Akt pathway and its downstream substrate
      NF-kappaB on prostate cancer bone metastatic process. Expression level of active
      p-Akt in PC3 cells was upregulated by transient expression with constitutively
      active plasmid CA-Akt or, alternatively, suppressed by dominant negative
      construct DN-Akt. NF-kappaB activity was determined by luciferase reporter
      assays. mRNA and protein expressions of receptor activator of NF-kappaB ligand
      (RANKL), parathyroid hormone-related protein (PTHrP), and bone morphogenetic
      protein 2 (BMP-2) were evaluated using RT-PCR and Western blotting. The effect of
      cross-talk between PC3 and SaOS2 cells on cell proliferation was analyzed using a
      co-culture system. Stimulation of p-Akt promoted NF-kappaB activity, and led to
      an increase in mRNA and protein expressions of RANKL, PTHrP, and BMP-2 in PC3 PCa
      cells through NF-kappaB. Co-culturing PC3 and SaOS2 cells significantly increased
      the expression of p-Akt and the activity of NF-kappaB, and promoted proliferation
      of both PC3 and SaOS2 cells. Increasing expression levels of p-Akt by
      transfection with CA-Akt led to further increase in cells proliferation, whereas
      NF-kappaB inhibitor PDTC partially blocked this effect. PI3K/Akt pathway
      stimulates the expressions of RANKL, PTHrP, and BMP-2 partly through NF-kappaB,
      suggesting its importance for bone metastasis of prostate carcinoma. Interaction
      of prostate cancer cells with bone cells has a stimulatory effect on cell
      proliferation.

PMID- 27040946
TI  - Antagonism of miRNA-21 Sensitizes Human Gastric Cancer Cells to Paclitaxel.
AB  - The development of drug resistance has largely limited the clinical outcome of
      anti-cancer treatment. Recent work has highlighted the involvement of non-coding
      RNAs, microRNAs (miRNAs), in cancer development. The present study aimed to
      investigate the role of miR-21 in the development of drug resistance to
      paclitaxel in gastric cancer cells. Our study found that the expression of miR-21
      upregulated in the paclitaxel resistant cell line SGC7901/paclitaxel compared to
      its parental line SGC7901. Moreover, over-expression of miR-21 significantly
      decreased antiproliferative effects and apoptosis induced by paclitaxel, while
      knockdown of miR-21 dramatically increased antiproliferative effects and
      apoptosis induction by paclitaxel. Moreover, our results demonstrated that miR-21
      may modulate the sensitivity to PTX, at least in part, by regulating the
      expression of P-glycoprotein.

PMID- 27040947
TI  - Tumor penetrating peptides for improved drug delivery.
AB  - In vivo screening of phage libraries in tumor-bearing mice has been used to
      identify peptides that direct phage homing to a tumor. The power of in vivo phage
      screening is illustrated by the recent discovery of peptides with unique tumor
      penetrating properties. These peptides activate an endocytic transport pathway
      related to but distinct from macropinocytosis. They do so through a complex
      process that involves binding to a primary, tumor-specific receptor, followed by
      a proteolytic cleavage, and binding to a second receptor. The second receptor,
      neuropilin-1 (or neuropilin-2) activates the transport pathway. This trans-tissue
      pathway, dubbed the C-end Rule (CendR) pathway, mediates the extravasation
      transport through extravascular tumor tissue of payloads ranging from small
      molecule drugs to nanoparticles. The CendR technology provides a solution to a
      major problem in tumor therapy, poor penetration of drugs into tumors. Targeted
      delivery with tumor-penetrating peptides has been shown to specifically increase
      the accumulation of drugs, antibodies and nanotherapeutics in experimental tumors
      in vivo, and in human tumors ex vivo. Remarkably the payload does not have to be
      coupled to the peptide; the peptide activates a bulk transport system that sweeps
      along a drug present in the blood. Treatment studies in mice have shown improved
      anti-tumor efficacy and less damage to normal tissues with drugs ranging from
      traditional chemotherapeutics to antibodies, and to nanoparticle drugs.

PMID- 27040948
TI  - Renal tubular injury induced by ischemia promotes the formation of calcium
      oxalate crystals in rats with hyperoxaluria.
AB  - Hyperoxaluria and cell injury are key factors in urolithiasis. Oxalate metabolism
      may be altered by renal dysfunction and therefore, impact the deposition of
      calcium oxalate (CaOx) crystals. We investigated the relationship of renal
      function, oxalate metabolism and CaOx crystal deposition in renal ischemia. One
      hundred male Sprague-Dawley rats were randomly divided into four groups.
      Hyperoxaluria model (Group A and B) was established by feeding rats with 0.75 %
      ethylene glycol (EG). The left renal pedicle was clamped for 30 min to establish
      renal ischemia Groups (B and C), while Groups A and D underwent sham operation.
      Then, serum and urine oxalate (Ox), creatinine (Cr) and urea nitrogen (UN) levels
      were evaluated by liquid chromatography mass spectrometry (LCMS) and ion mass
      spectrum (IMS) at days 0, 2, 4, 7, and 14. CaOx crystallization was assessed by
      transmission electron microscope (TEM). A temporal and significant increase of
      serum Cr and UN levels was observed in Groups B and C compared to values obtained
      for Groups A and D (P < 0.05). Ox levels in serum and urine were significantly
      higher in Groups A and B than in the other two groups from day 7 (P < 0.05). In
      addition, CaOx crystallization was observed in both Groups A and B, but Group B
      showed earlier and more pronounced crystal deposition in the renal tissue. Our
      results indicated that renal tubular injury induced by renal ischemia might not
      affect Ox levels but could promote CaOx crystal retention under hyperoxaluria. 

PMID- 27040949
TI  - Effect of anxiety and pain on success of shockwave lithotripsy (SWL) for
      treatment of proximal ureteral and renal pelvic stones.
AB  - The aim of this study is to evaluate the impact of anxiety and pain on success of
      shockwave lithotripsy (SWL) for treatment of proximal ureteral and renal pelvic
      stones smaller than 15 mm. One hundred thirty-two patients with proximal ureteral
      or renal pelvic stones <15 mm who were treated by a SWL and forty controls were
      enrolled in the study. State-trait anxiety inventory (STAI) was used to assess
      anxiety of the controls and patients (before every SWL session). Pains of the
      patients were measured by a visual analog scale (VAS) at three times (T) of the
      sessions (T11 at 11 kV, T15 at 15 kV and T end of treatment). The mean STAI
      scores of the patients at the first SWL session and controls were 40.61 +/- 8.71
      and 36.11 +/- 8.18, respectively (p < 0.05). There was statistically positive
      moderate relationship between STAI and VAS scores at the first SWL session. The
      mean size of stone in men and women were 11.16 +/- 2.88 and 11.00 +/- 3.41,
      respectively (p = 0.88). In the first session, the mean STAI and VAS scores of
      the men were significantly lower than the women. The stone-free rate (SFR) of SWL
      was 72.7 % in this study. The SFR of SWL in the men and women were 78 and 64 %,
      respectively (p < 0.05). Our data showed that the severity of anxiety and pain in
      the women were higher than the men. SFR of SWL in the men was higher than the
      women. The severity of anxiety and pain in the patients may affect SFR of SWL.

PMID- 27040950
TI  - Using positive images to manage resistance-to-care and combative behaviors in
      nursing home residents with dementia: A pilot study.
AB  - This pilot study attempted to reduce resistance-to-care (RTC) and combative
      behaviors in nursing home residents with dementia by eliciting their positive
      affect. Four female residents with dementia were recruited from a nursing
      facility. Each resident was involved in one intervention trial and one control
      trial. The response of the residents was assessed by the Agitated Behavior Scale
      and the Observational Measurement of Engagement Tool. The distress level of the
      certified nursing assistants (CNAs) delivering the care was reported through the
      Distress Thermometer. Results showed that the residents displayed fewer
      behavioral symptoms in the intervention trial than in the control trial. The CNAs
      reported less distress in the intervention trial than in the control trial. These
      preliminary findings suggest that it might be feasible to use positive images to
      reduce residents' behavioral symptoms and decrease the distress of CNAs.

PMID- 27040951
TI  - Sports drug testing using complementary matrices: Advantages and limitations.
AB  - Today, routine doping controls largely rely on testing whole blood, serum, and
      urine samples. These matrices allow comprehensively covering inorganic as well as
      low and high molecular mass organic analytes relevant to doping controls and are
      collecting and transferring from sampling sites to accredited anti-doping
      laboratories under standardized conditions. Various aspects including time and
      cost-effectiveness as well as intrusiveness and invasiveness of the sampling
      procedure but also analyte stability and breadth of the contained information
      have been motivation to consider and assess values potentially provided and added
      to modern sports drug testing programs by alternative matrices. Such alternatives
      could be dried blood spots (DBS), dried plasma spots (DPS), oral fluid (OF),
      exhaled breath (EB), and hair. In this review, recent developments and test
      methods concerning these alternative matrices and expected or proven
      contributions as well as limitations of these specimens in the context of the
      international anti-doping fight are presented and discussed, guided by current
      regulations for prohibited substances and methods of doping as established by the
      World Anti-Doping Agency (WADA). Focusing on literature published between 2011
      and 2015, examples for doping control analytical assays concerning non-approved
      substances, anabolic agents, peptide hormones/growth factors/related substances
      and mimetics, beta2-agonists, hormone and metabolic modulators, diuretics and
      masking agents, stimulants, narcotics, cannabinoids, glucocorticoids, and beta
      blockers were selected to outline the advantages and limitations of the
      aforementioned alternative matrices as compared to conventional doping control
      samples (i.e. urine and blood/serum).

PMID- 27040952
TI  - Chlorambucil conjugates of dinuclear p-cymene ruthenium trithiolato complexes:
      synthesis, characterization and cytotoxicity study in vitro and in vivo.
AB  - Four diruthenium trithiolato chlorambucil conjugates have been prepared via
      Steglich esterification from chlorambucil and the corresponding trithiolato
      precursors. All conjugates are highly cytotoxic towards human ovarian A2780 and
      A2780cisR cancer cell lines with IC50 values in the nanomolar range. The
      conjugates exhibit selectivity towards A2780 cells as compared to non-cancerous
      HEK293 cells, while being only slightly selective for RF24 and A2780cisR cells.
      In vivo, the conjugate [10]BF4 suppressed the growth of a solid Ehrlich tumor in
      immunocompetent NMRI mice but did not prolong their overall survival. The
      reactivity of the chlorambucil conjugates with glutathione, a potential target of
      the dinuclear ruthenium motive, and with the 2-deoxyguanosine 5'-monophosphate
      (dGMP-a model target of chlorambucil) was studied by mass spectrometry and NMR
      spectroscopy. The conjugates did not show catalytic activity for the oxidation of
      glutathione nor binding to nucleotides, indicating that glutathione oxidation and
      DNA alkylation are not key mechanisms of action. Four highly cytotoxic
      diruthenium trithiolato chlorambucil conjugates have been prepared. All
      conjugates exhibit selectivity towards A2780 cells as compared to HEK293 cells,
      while being only slightly active in RF24 and A2780cisR cells. In vivo, the best
      candidate suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI
      mice but did not prolong their overall survival.

PMID- 27040953
TI  - Effect of temperature on the interaction of cisplatin with the model protein hen
      egg white lysozyme.
AB  - The products of the reaction between cisplatin (CDDP) and the model protein hen
      egg white lysozyme (HEWL) at 20, 37 and 55  degrees C in pure water were studied
      by UV-Vis absorption spectroscopy, intrinsic fluorescence and circular dichroism,
      dynamic and electrophoretic light scattering and inductively coupled plasma mass
      spectrometry. X-ray structures were also solved for the adducts formed at 20 and
      55  degrees C. Data demonstrate that high temperature facilitates the formation
      of CDDP-HEWL adducts, where Pt atoms bind ND1 atom of His15 or NE2 atom of His15
      and NH1 atom of Arg14. Our study suggests that high human body temperature
      (fever) could increase the rate of drug binding to proteins thus enhancing
      possible toxic side effects related to CDDP administration.

PMID- 27040954
TI  - Introduction: The Complexity and Challenge of Preventing, Treating, and Managing
      Blood Diseases in the Developing Countries.
AB  - Managing hematologic disorders in developing countries poses problems not
      encountered in Western societies. The clinical features of hematologic conditions
      may be modified by malnutrition, chronic bacterial infection, or parasitic
      illness. Iron deficiency is the major factor in anemia worldwide. Anemia is more
      common in the wet season when malaria transmission peaks. After anemia,
      eosinophilia is the next most common hematologic abnormality in children in the
      tropics. Infection with the human immunodeficiency virus can cause hematologic
      abnormalities. The pattern of distribution of primary disorders of the blood
      varies among populations and some disorders are unique to certain parts of the
      world. 

PMID- 27040955
TI  - The Global Burden of Anemia.
AB  - Anemia is an important cause of health loss. We estimated levels and trends of
      nonfatal anemia burden for 23 distinct etiologies in 188 countries, 20 age
      groups, and both sexes from 1990 to 2013. All available population-level anemia
      data were collected and standardized. We estimated mean hemoglobin, prevalence of
      anemia by severity, quantitative disability owing to anemia, and underlying
      etiology for each population using the approach of the Global Burden of Disease,
      Injuries and Risk Factors 2013 Study. Anemia burden is high. Developing countries
      account for 89% of all anemia-related disability. Iron-deficiency anemia remains
      the dominant cause of anemia. 

PMID- 27040956
TI  - Iron Deficiency Anemia: Problems in Diagnosis and Prevention at the Population
      Level.
AB  - Anemia is common among people living in low- and middle-income countries, and
      alleviation of the global burden of anemia is an essential global health target
      over the next decade. Estimates have attributed about half the cases of anemia
      worldwide to iron deficiency; a range of other causes probably make a similar
      overall contribution. Individuals living in low-income settings experience a
      simultaneous high burden of infection with inflammation and iron deficiency. At
      least in children, iron supplementation exacerbates the risk of infection in both
      malaria-endemic and nonendemic low-income countries, whereas iron deficiency is
      protective against clinical and severe malaria. 

PMID- 27040957
TI  - The Present and Future Global Burden of the Inherited Disorders of Hemoglobin.
AB  - The inherited disorders of hemoglobin represent the most common monogenic
      diseases. This article provides a brief description of the main inherited
      disorders of hemoglobin and their classification, and summarizes progress made in
      the last decade toward a better awareness and recognition of these disorders as a
      global health problem. Also presented are the main demographic, genetic, and
      environmental factors that influence the present and future health burden of
      these disorders. The strengths and limitations of existing estimates and current
      health policies in high-, low-, and middle-income countries are discussed. 

PMID- 27040958
TI  - Sickle Cell Disease in Sub-Saharan Africa.
AB  - In Africa, at least 240,000 children are born each year with sickle cell disease.
      Historically, in the absence of newborn screening and appropriate treatment, most
      such children died undiagnosed in early childhood. However, with increasing
      awareness of the condition and economic and epidemiologic transition, increasing
      numbers are surviving. Greater investments in basic and applied research in the
      African context, and increased sensitization or African ministries of health
      regarding the importance of this condition, could make a substantial difference
      to the lives and livelihoods of millions of people living with sickle cell
      disease on the continent and their families. 

PMID- 27040959
TI  - Progress Toward the Control and Management of the Thalassemias.
AB  - Because of the particularly high frequency of different severe forms of both
      alpha and beta thalassemia in Asia, the development of approaches for their
      prevention and management is particularly challenging. However, because of
      earlier partnerships with richer countries, so-called North/South partnerships,
      and help from their governments, considerable progress toward the better control
      of the thalassemias has been achieved in some countries. It is vital that the
      global health importance of the thalassemias and related disorders, by far the
      commonest genetic diseases, is emphasized to the appropriate international health
      agencies. 

PMID- 27040960
TI  - Glucose-6-Phosphate Dehydrogenase Deficiency.
AB  - G6PD is a housekeeping gene expressed in all cells. Glucose-6-phosphate
      dehydrogenase (G6PD) is part of the pentose phosphate pathway, and its main
      physiologic role is to provide NADPH. G6PD deficiency, one of the commonest
      inherited enzyme abnormalities in humans, arises through one of many possible
      mutations, most of which reduce the stability of the enzyme and its level as red
      cells age. G6PD-deficient persons are mostly asymptomatic, but they can develop
      severe jaundice during the neonatal period and acute hemolytic anemia when they
      ingest fava beans or when they are exposed to certain infections or drugs. G6PD
      deficiency is a global health issue. 

PMID- 27040961
TI  - Hematologic Changes Associated with Specific Infections in the Tropics.
AB  - Anemia frequently accompanies and plays a minor role in the presentation and
      course of infection, whether parasitic, bacterial, or viral. However, a variety
      of infections, many of which are common in Africa and Asia, cause specific
      hematologic syndromes. The pathophysiology of these syndromes is complex, and to
      some extent, reduced red cell production may form part of an innate protective
      host response to infection. Across the world and in endemic areas, malaria is the
      most important among this group of infections and forms a major part of everyday
      practice. 

PMID- 27040962
TI  - Global Approach to Hematologic Malignancies.
AB  - Treatment of childhood hematologic malignancies requires multidisciplinary care
      and reliable infrastructural support; creating a this structure in resource-poor
      settings remains challenging. Ideally therapy would be tailored to each region
      and disease. The development of research initiatives is essential. Acute
      lymphoblastic leukemia (ALL) and lymphomas are common in low- and middle-income
      countries; treatment is often resource intense but likely cost effective.
      Outcomes currently are worse than those reported in high-income countries.
      Chronic myeloid leukemia can be treated effectively with imatinib. Strategies to
      decrease the burden of therapy and robust palliative care programs are essential
      for optimal treatment of all afflicted children. 

PMID- 27040963
TI  - Hematological Practice in India.
AB  - This article provides a short summary of hematological practice in India. It
      focuses particularly on how the patterns of hematologic practice differ from
      those of countries in the West with particular respect to genetic hematological
      diseases and a wide range of malignant disorders of hemopoiesis. It also focuses
      on the difficulties of control and management of hematological disorders set
      against a background of a relatively poor country. 

PMID- 27040964
TI  - Hematological Practice in Hong Kong and China.
AB  - Thalassemias and hemophilias are the most important inherited hematological
      diseases in Hong Kong and China. Prenatal diagnosis has significantly decreased
      the burden of these diseases. For thalassemia major, adequate transfusion and
      iron chelation therapy have dramatically improved patient outlook. Hematopoietic
      stem cell transplantation is curative for thalassemia major and is increasingly
      adopted. The efficacy of arsenic trioxide in acute promyelocytic leukemia (APL)
      was discovered in China. An oral formulation of arsenic trioxide was developed in
      Hong Kong for newly diagnosed and relapsed APL patients. With combination
      chemotherapy containing non-P-glycoprotein-dependent drugs and L-asparaginase,
      durable remission can be achieved in the most patients. 

PMID- 27040965
TI  - Hematology in Africa.
AB  - This review of hematology in Africa highlights areas of current practice and the
      immediate needs for development and clinical research. Acute hematological
      practice is dominated by anemia, sickle cell disease, and the need to provide a
      safe and rapidly available supply of blood. There is a growing need for
      specialist services for bleeding and coagulation, hematological malignancy, and
      palliative care. There are many areas of practice where straightforward measures
      could yield large gains in patient care. There is an urgent need for good
      clinical research to describe the epidemiology, natural history, and management
      of hematological diseases in Africa. 

PMID- 27040966
TI  - Problems and Approaches for Blood Transfusion in the Developing Countries.
AB  - A safe supply of blood and the knowledge, skill, and resources for the
      appropriate use of blood are essential for medical services. Many problems are
      faced in the development of transfusion services in low- or medium-income
      countries (LMICs). Unfortunately, in many countries, providing safe blood is made
      more difficult by a lack of blood donors and the high frequency of transfusion
      transmissible infections. The problems are compounded by the frequent need for
      urgent life-saving transfusions. This article examines the problems in supply,
      safety, and use of blood and how they are being addressed in LMICs, predominantly
      focusing on sub-Saharan Africa. 

PMID- 27040967
TI  - Improving Laboratory and Clinical Hematology Services in Resource Limited
      Settings.
AB  - The difficulties in establishing and delivering reliable clinical hematology and
      laboratory services in resource-limited settings are well recognized. However,
      much can be achieved by better use of existing resources through a concerted
      quality improvement approach. The recommendations of this article are based in
      part upon work in the thalassemias, inherited disorders of hemoglobin that are
      widely prevalent in Asia, which may serve as a model that is applicable to other
      common, chronic disorders in resource-poor settings. Available resources are
      highlighted and recommendations made regarding approaches to improving services.
      Over the last few years, a number of low and middle-income countries, obtaining
      support from appropriate governmental sources, have identified and overcome
      difficulties and significantly improved clinical services for patients with
      thalassemia. 

PMID- 27040968
TI  - Global Hematology.

PMID- 27040969
TI  - Using a One Health approach to assess the impact of parasitic disease in
      livestock: how does it add value?
AB  - Human population increases, with greater food demands, have resulted in a rapid
      evolution of livestock food systems, leading to changes in land and water use.
      The scale of global livestock systems mean that changes in animal health status,
      particularly in parasite levels, have impacts that go beyond farm and sector
      levels. To quantify the true impact of parasites in livestock, frameworks that
      look at both resources and services valued in markets and those that have no true
      market value are required. Mitigating the effects of parasitic disease in
      livestock will not only increase productivity, but also improve animal welfare
      and human health, whilst reducing the environmental burden of livestock
      production systems. To measure these potential benefits, a One Health approach is
      needed. This paper discusses the types of methods and the data collection tools
      needed for a more holistic perspective and provides a framework with its
      application to coccidiosis in poultry. To build a body of knowledge that allows
      the ranking of parasite diseases in a wider animal health setting, such One
      Health frameworks need to be applied more frequently and with rigour. The outcome
      will improve the allocation of resources to critical constraints on parasite
      management.

PMID- 27040970
TI  - Noisy threshold in neuronal models: connections with the noisy leaky integrate
      and-fire model.
AB  - Providing an analytical treatment to the stochastic feature of neurons' dynamics
      is one of the current biggest challenges in mathematical biology. The noisy leaky
      integrate-and-fire model and its associated Fokker-Planck equation are probably
      the most popular way to deal with neural variability. Another well-known
      formalism is the escape-rate model: a model giving the probability that a neuron
      fires at a certain time knowing the time elapsed since its last action potential.
      This model leads to a so-called age-structured system, a partial differential
      equation with non-local boundary condition famous in the field of population
      dynamics, where the age of a neuron is the amount of time passed by since its
      previous spike. In this theoretical paper, we investigate the mathematical
      connection between the two formalisms. We shall derive an integral transform of
      the solution to the age-structured model into the solution of the Fokker-Planck
      equation. This integral transform highlights the link between the two stochastic
      processes. As far as we know, an explicit mathematical correspondence between the
      two solutions has not been introduced until now.

PMID- 27040971
TI  - A serine protease inhibitor from Musca domestica larva exhibits inhibitory
      activity against elastase and chymotrypsin.
AB  - OBJECTIVE: Insect-derived serine protease inhibitors (serpins) exhibit multiple
      inhibitory activities, but so far, no functional roles for serpins of Musca
      domestica have been identified. Here, the functional features of M. domestica
      serine protease inhibitor (MDSPI16) were characterized. RESULTS: Hundred forty
      seven differentially expressed genes including the MDSPI16 gene were screened by
      constructing the subtractive cDNA library. The 1154-bp full-length MDSPI16 gene
      was cloned, and the recombinant MDSPI16 serpin protein was expressed as a 42.6
      kDa protein in an Escherichia coli expression system. The recombinant MDSPI16
      protein was purified using Ni-NTA affinity chromatography, and the inhibitory
      activity of MDSPI16 was assessed. MDSPI16 did not inhibit trypsin, papain, or
      proteinase K but strongly inhibited elastase (Ki = 2.8 nM) and chymotrypsin (Ki =
      28 nM). The inhibitory activity of MDSPI16 remained stable over from 37 to 100 
      degrees C and from pH 2 to 12. CONCLUSIONS: The MDSPI16 exhibited inhibitory
      activity against elastase and chymotrypsin and the inhibitory activity remained
      stable.

PMID- 27040972
TI  - Gamblers Anonymous as a Recovery Pathway: A Scoping Review.
AB  - Given the preponderance of Gamblers Anonymous (GA), there has been relatively
      little effort to explore the existing evidence base on its effectiveness as a
      recovery approach for problem gambling. To remedy this gap in the literature we
      conducted a scoping review of the literature on mutual aid for individuals
      experiencing problem gambling published between 2002 and 2015. We searched 13
      databases and reviewed reference lists and websites of relevant organizations. We
      reviewed records for eligibility and extracted relevant data from eligible
      articles. Three reviewers independently assessed the methodological quality of
      the included studies using the Mixed Methods Appraisal Tool. We identified 17
      studies in 25 publications that were eligible for inclusion. Most studies were
      conducted in the United States, were cross-sectional in design, and involved both
      male and female adult participants. Results indicate that the evidence for the
      effectiveness of GA either as a control condition or in conjunction with formal
      treatment or medication is inconsistent. An emphasis on patience, using the
      Serenity Prayer as a way to gain acceptance of financial matters and reality, and
      absolute assertion of identity as a "compulsive gambler" were identified as
      important aspects of GA's recovery culture. There is a need for large-scale
      randomized controlled trials to determine GA's effectiveness, as well as research
      exploring the mechanisms through which GA works, barriers to GA as a recovery
      approach, and the status of women in the fellowship.

PMID- 27040973
TI  - Treating Problem Gambling Samples with Cognitive Behavioural Therapy and
      Mindfulness-Based Interventions: A Clinical Trial.
AB  - The problem gambling (PG) intervention literature is characterised by a variety
      of psychological treatments and approaches, with varying levels of evidence
      (PGRTC in Guideline for screening, assessment and treatment in problem and
      pathological gambling. Monash University, Melbourne, 2011). A recent PG
      systematic review (Maynard et al. in Res Soc Work Pract, 2015. doi:
      10.1177/1049731515606977 ) and the success of mindfulness-based interventions to
      effectively treat disorders commonly comorbid with PG suggested mindfulness-based
      interventions may be effective for treating PG. The current study tested the
      effectiveness of three interventions to treat PGs: 1. case formulation driven
      Cognitive Behaviour Therapy (CBT); 2. manualised CBT; and 3. mindfulness-based
      treatment. All three interventions tested returned large effect size improvements
      in PG behaviour after seven sessions (Cohen's d range 1.46-2.01), at post
      treatment and at 3 and 6-month follow-up. All of the interventions were rated as
      acceptable by participants at post-treatment. This study suggests that the
      mindfulness-based and TAU interventions used in the current study appear to be
      effective at reducing PG behavior and associated distress and they also appear to
      generalise to improvements in other measures such as quality of life-mental
      functioning and certain mindfulness facets more effectively than the manualised
      form of CBT utilised used here. Secondly, a brief mindfulness intervention
      delivered after psycho-education and a brief CBT intervention may be a useful
      supplement to traditional CBT treatments by addressing transdiagnostic processes
      such as rumination and thought suppression. Thirdly, CBT interventions continue
      to report effectiveness in reducing PG behaviour and associated distress
      consistent with the prevailing literature and clinical direction.

PMID- 27040974
TI  - American tegumentary leishmaniasis: T-cell differentiation profile of cutaneous
      and mucosal forms-co-infection with Trypanosoma cruzi.
AB  - American tegumentary leishmaniasis displays two main clinical forms: cutaneous
      (CL) and mucosal (ML). ML is more resistant to treatment and displays a more
      severe and longer evolution. Since both forms are caused by the same Leishmania
      species, the immunological response of the host may be an important factor
      determining the evolution of the disease. Herein, we analyzed the differentiation
      and memory profile of peripheral CD4(+) and CD8(+) T lymphocytes of patients with
      CL and ML and their Leishmania-T. cruzi co-infected counterparts. We measured the
      expression of CD27, CD28, CD45RO, CD127, PD-1 and CD57, together with interferon
      gamma and perforin. A highly differentiated phenotype was reflected on both T
      subsets in ML and preferentially on CD8(+) T cells in CL. A positive trend toward
      a higher T differentiation profile was found in T. cruzi-infected CL and ML
      patients as compared with Leishmania single infections. Association between
      CD8(+) T-cell differentiation and illness duration was found within the first
      year of infection, with progressive increase of highly differentiated markers
      over time. Follow-up of patients with good response to therapy showed
      predominance of early differentiated CD8(+) T cells and decrease of highly
      differentiated cells, while patients with frequent relapses presented the
      opposite pattern. CD8(+) T cells showed the most striking changes in their
      phenotype during leishmaniasis. Patients with long-term infections showed the
      highest differentiated degree implying a relation between T differentiation and
      parasite persistence. Distinct patterns of CD8(+) T differentiation during follow
      up of different clinical outcomes suggest the usefulness of this analysis in the
      characterization of Leishmania-infected patients. 

PMID- 27040975
TI  - Vibrational spectroscopy to support the link between rheology and continuous twin
      screw melt granulation on molecular level: A case study.
AB  - Twin screw hot melt granulation (TSHMG) is an innovative and continuous drug
      formulation process allowing granulation of moisture sensitive drugs. However,
      due to the lack of experience and in-depth process understanding, this technique
      is not yet widely used. During the TSHMG process, the microstructure of the
      granules is generated and modified and strongly depends on the flow behavior of
      the material. Hence, rheology might be a suitable tool to simulate and examine
      this process. However, chemical interactions of the material are influencing the
      physical properties leading to the microstructure. In this research project it is
      spectroscopically investigated whether the heat applied in a rheometer induces
      the same molecular effects as these occurring during TSHMG of the model
      formulation caffeine anhydrous/Soluplus(r). Hence, it is evaluated whether
      rheology can be used as a simulation tool to improve the understanding of the
      material behavior at molecular level during continuous melt granulation.
      Therefore, in-line Raman spectroscopy is executed during TSHMG and in situ
      Fourier Transform Infra-red (FTIR) during oscillatory rheological experiments.
      The results from the in-line Raman monitoring revealed polymorph transition of
      caffeine anhydrous during twin screw melt granulation with Soluplus(r) which is
      stimulated depending on the binder concentration and/or granulation temperature.
      A correlation was seen between the FTIR spectra obtained during the rheological
      temperature ramp and the in-line collected Raman spectra during the melt
      granulation runs. The polymorphic conversion of caffeine anhydrous could be
      detected in the same temperature range with both techniques, proving the
      comparability of plate-plate rheometry and hot melt granulation (HMG) for this
      case with the used parameter settings. Process simulation using rheology combined
      with in situ FTIR seems a promising approach to increase process understanding
      and to facilitate binder and parameter selection for TSHMG. 

PMID- 27040976
TI  - [PCSK9 continues surprising us].

PMID- 27040977
TI  - Use of Medical Reserve Corps Volunteers in a Hospital-based Disaster Exercise.
AB  - Introduction The Medical Reserve Corps (MRC) is a national network of community
      based volunteer groups created in 2002 by the Office of the United States Surgeon
      General (Rockville, Maryland USA) to augment the nation's ability to respond to
      medical and public health emergencies. However, there is little evidence-based
      literature available to guide hospitals on the optimal use of medical volunteers
      and hesitancy on the part of hospitals to use them. Hypothesis/Problem This study
      sought to determine how MRC volunteers can be used in hospital-based disasters
      through their participation in a full-scale exercise. METHODS: A full-scale
      exercise was designed as a "Disaster Olympics," in which the Emergency Medicine
      residents were divided into teams tasked with completing one of the following
      five challenges: victim decontamination, mass casualty/decontamination tent
      assembly, patient triage and registration during a disaster, point of
      distribution (POD) site set-up and operation, and infection control management. A
      surge of patients potentially exposed to avian influenza was the scenario created
      for the latter three challenges. Some MRC volunteers were assigned clinical
      roles. These roles included serving as members of the suit support team for
      victim decontamination, distributing medications at the POD, and managing
      infection control. Other MRC volunteers functioned as "victim evaluators," who
      portrayed the potential avian influenza victims while simultaneously evaluating
      various aspects of the disaster response. The MRC volunteers provided feedback on
      their experience and evaluators provided feedback on the performance of the MRC
      volunteers using evaluation tools. RESULTS: Twenty-eight (90%) MRC volunteers
      reported that they worked well with the residents and hospital staff, felt the
      exercise was useful, and were assigned clearly defined roles. However, only 21
      (67%) reported that their qualifications were assessed prior to role assignment.
      For those MRC members who functioned as "victim evaluators," nine identified
      errors in aspects of the care they received and the disaster response. Of those
      who evaluated the MRC, nine (90%) felt that the MRC worked well with the
      residents and hospital staff. Ten (100%) of these evaluators recommended that MRC
      volunteers participate in future disaster exercises. CONCLUSION: Through use of a
      full-scale exercise, this study was able to identify roles for MRC volunteers in
      a hospital-based disaster. This study also found MRC volunteers to be uniquely
      qualified to serve as "victim evaluators" in a hospital-based disaster exercise.
      Gist R , Daniel P , Grock A , Lin C , Bryant C , Kohlhoff S , Roblin P , Arquilla
      B . Use of Medical Reserve Corps volunteers in a hospital-based disaster
      exercise. Prehosp Disaster Med. 2016;31(3):259-262.

PMID- 27040978
TI  - The influence of population mobility on changing patterns of HIV acquisition:
      lessons for and from Australia.
AB  - Investment, bipartisan support and involvement from affected communities have
      characterised Australia's HIV response, and helped maintain a low prevalence
      epidemic. Patterns of HIV acquisition are changing, with an increasing number of
      infections acquired overseas by migrant and mobile populations. A coordinated
      national response is required to address HIV acquisition in the context of
      population mobility.

PMID- 27040979
TI  - Rice protein suppresses ROS generation and stimulates antioxidant gene expression
      via Nrf2 activation in adult rats.
AB  - To elucidate the effects of rice protein on the detoxification and antioxidant
      defense via the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, adult
      rats were fed casein and rice protein under cholesterol-free and -enriched
      dietary conditions. Nrf2 proteins and gene expressions were stimulated by rice
      proteins with respect to caseins accompanied by up-regulating the expression of
      gene encoding antioxidant and phase II detoxification in the rice protein groups.
      In the liver, compared with caseins, rice proteins significantly increased
      hepatic contents of reduced glutathione (GSH) and mRNA levels of glutamate
      cysteine ligase catalytic subunit (GCLC), glutamate cysteine ligase modulatory
      subunit (GCLM), glutathione S-transferase (GST), heme oxygenase 1 (HO-1) and
      NAD(P)H: quinone oxidoreductase 1 (NQO1), whereas hepatic accumulations of
      reactive oxygen species (ROS) and oxidized glutathione (GSSG) were markedly
      depressed in adult rats fed rice proteins. The present study demonstrates the
      endogenous antioxidant potential of rice proteins via mechanism through which
      Nrf2 activation plays an essential role in inducing Phase II
      antioxidants/detoxification enzymes and preventing ROS generation. This novel
      antioxidative function of rice protein is independent of dietary cholesterol
      during in adult rats.

PMID- 27040980
TI  - Androgen-inducible gene 1 increases the ER Ca(2+) content and cell death
      susceptibility against oxidative stress.
AB  - Androgen-induced gene 1 (AIG1) is a transmembrane protein implicated with
      survival (its expression level was shown to correlate with the survival of
      patients suffering from hepatocellular carcinoma) and Ca(2+) signaling (over
      expression of AIG1 increased transcription mediated by the Ca(2+)-dependent
      nuclear factor of activated T cells). We aimed to shed light on this less-studied
      protein and investigated its tissue expression, genomic organization,
      intracellular localization and membrane topology as well as its effects on cell
      death susceptibility and the Ca(2+) content of the endoplasmic reticulum.
      Immunoblotting of mouse tissues demonstrated highest expression of AIG1 in the
      liver, lung and heart. AIG1 has a complex genomic organization and expresses
      several splice variants in a tissue-dependent manner. Analyzing the topology of
      AIG1 in the ER membrane using a protease-protection assay suggested that AIG has
      five transmembrane domains with a luminal N- and cytosolic C-terminus and a
      hydrophobic stretch between the third and fourth membrane domain that does not
      cross the membrane. AIG1 over-expression slightly increased susceptibility to
      oxidative stress, which correlated with an increased ER Ca(2+) concentration in
      two different cell lines. Together, these results indicate that AIG1 plays a role
      in the control of the intracellular Ca(2+) concentration and cell death
      susceptibility. 

PMID- 27040981
TI  - RepA-WH1 prionoid: Clues from bacteria on factors governing phase transitions in
      amyloidogenesis.
AB  - In bacterial plasmids, Rep proteins initiate DNA replication by undergoing a
      structural transformation coupled to dimer dissociation. Amyloidogenesis of the
      'winged-helix' N-terminal domain of RepA (WH1) is triggered in vitro upon binding
      to plasmid-specific DNA sequences, and occurs at the bacterial nucleoid in vivo.
      Amyloid fibers are made of distorted RepA-WH1 monomers that assemble as single or
      double intertwined tubular protofilaments. RepA-WH1 causes in E. coli an amyloid
      proteinopathy, which is transmissible from mother to daughter cells, but not
      infectious, and enables conformational imprinting in vitro and in vivo; i.e. RepA
      WH1 is a 'prionoid'. Microfluidics allow the assessment of the intracellular
      dynamics of RepA-WH1: bacterial lineages maintain two types (strains-like) of
      RepA-WH1 amyloids, either multiple compact cytotoxic particles or a single
      aggregate with the appearance of a fluidized hydrogel that it is mildly
      detrimental to growth. The Hsp70 chaperone DnaK governs the phase transition
      between both types of RepA-WH1 aggregates in vivo, thus modulating the vertical
      propagation of the prionoid. Engineering chimeras between the Sup35p/[PSI(+)]
      prion and RepA-WH1 generates [REP-PSI(+)], a synthetic prion exhibiting strong
      and weak phenotypic variants in yeast. These recent findings on a synthetic, self
      contained bacterial prionoid illuminate central issues of protein
      amyloidogenesis. 

PMID- 27040982
TI  - Analysis of Tea Geometrid (Ectropis grisescens) Pheromone Gland Extracts Using GC
      EAD and GC*GC/TOFMS.
AB  - The tea geometrid, Ectropis grisescens Warren, is one of the most severe
      defoliator insect pests in tea plantations, China. The use of insecticides, etc.,
      is forbidden on organic tea plantations. No female-produced sex pheromones of E.
      grisescens had been previously identified. In the present study, female gland
      extracts were analyzed by gas chromatography coupled with electroantennographic
      detection (GC-EAD) and two-dimensional gas chromatography (GC*GC) using a time-of
      flight mass spectrometric detector (TOFMS). Two components, (Z,Z,Z)-3,6,9
      octadecatriene (Z3Z6Z9-18:Hy) and (Z,Z)-3,9-6,7-epoxyoctadecadiene (Z3Z9-6,7-epo
      18:Hy), were identified from pheromone gland extracts, and their
      electrophysiological and behavioral activity evaluated. Under laboratory
      conditions, Z3Z9-6,7-epo-18:Hy elicited a stronger electrophysiological response
      than Z3Z6Z9-18:Hy. In the field, traps baited with Z3Z9-6,7-epo-18:Hy alone
      showed better results than traps baited with Z3Z6Z9-18:Hy, and the binary mixture
      of Z3Z9-6,7-epo-18:Hy and Z3Z6Z9-18:Hy in a ratio of 4:1 (approximate ratio of
      females emitting pheromone) caught more males than the single components or any
      other blends. This study showed that Z3Z6Z9-18:Hy and Z3Z9-6,7-epo-18:Hy are the
      sex pheromone components of E. grisescens and that they prove useful in
      developing alternative management tools for the pest. 

PMID- 27040983
TI  - A Fast and Sensitive Method for the Detection of Leuprolide Acetate: A High
      Throughput Approach for the In Vitro Evaluation of Liquid Crystal Formulations.
AB  - The suitability of using fluorescence spectroscopy to rapidly assay drug release
      by quantifying the time-dependent increase in total intrinsic protein
      fluorescence was assessed. Leuprolide acetate, a synthetic nonapeptide analogue
      of gonadotropin-releasing hormone (GnRH or LHRH), is the active pharmaceutical
      ingredient used to treat a wide range of sex hormone-related disorders, including
      advanced prostatic cancer, endometriosis, and precocious puberty. During the in
      vitro evaluation of drug delivery technologies for leuprolide acetate, one of the
      most time-consuming steps is the detection and accurate quantification of
      leuprolide release from formulation candidates. Thus far, the dominant means for
      leuprolide detection involves conventional multistep high-performance liquid
      chromatography (HPLC) methods, requiring sampling, dilutions, sample filtration,
      and chromatography, which can take up to 40 min for each sample. With the
      increasing demand for assay adaptation to high-throughput format, here we sought
      to exploit fluorescence spectroscopy as a tool to develop a novel method to
      rapidly assay the in vitro release of leuprolide acetate. By utilizing the
      intrinsic fluorescence of the tryptophan (Trp) and tyrosine (Tyr) amino acid
      residues present in the leuprolide nonapeptide, the in vitro release from liquid
      crystal formulations was accurately quantified as a function of fluorescence
      intensity. Here, we demonstrate that assaying leuprolide release using intrinsic
      protein fluorescence in a 96-well format requiring volumes as low as 100 MUL is a
      cost-effective, rapid, and highly sensitive alternative to conventional HPLC
      methods. Furthermore, the high signal-to-noise ratios and robust Z'-factors of
      >0.8 indicate high sensitivity, precision, and feasibility for miniaturization,
      high-throughput format adaptation, and automation.

PMID- 27040985
TI  - A role for TENM1 mutations in congenital general anosmia.
AB  - Congenital general anosmia (CGA) is a neurological disorder entailing a complete
      innate inability to sense odors. While the mechanisms underlying vertebrate
      olfaction have been studied in detail, there are still gaps in our understanding
      of the molecular genetic basis of innate olfactory disorders. Applying whole
      exome sequencing to a family multiply affected with CGA, we identified three
      members with a rare X-linked missense mutation in the TENM1 (teneurin 1) gene
      (ENST00000422452:c.C4829T). In Drosophila melanogaster, TENM1 functions in
      synaptic-partner-matching between axons of olfactory sensory neurons and target
      projection neurons and is involved in synapse organization in the olfactory
      system. We used CRISPR-Cas9 system to generate a Tenm1 disrupted mouse model.
      Tenm1(-/-) and point-mutated Tenm1(A) (/A) adult mice were shown to have an
      altered ability to locate a buried food pellet. Tenm1(A) (/A) mice also displayed
      an altered ability to sense aversive odors. Results of our study, that describes
      a new Tenm1 mouse, agree with the hypothesis that TENM1 has a role in olfaction.
      However, additional studies should be done in larger CGA cohorts, to provide
      statistical evidence that loss-of-function mutations in TENM1 can solely cause
      the disease in our and other CGA cases.

PMID- 27040986
TI  - Major Pulmonary Complications After Hematopoietic Stem Cell Transplant.
AB  - Both autologous and allogeneic hematopoietic stem cell transplants are important
      therapeutic options for several benign and malignant disorders. Pulmonary
      complications, although they have become less frequent, remain a significant
      cause of morbidity and mortality after hematopoietic stem cell transplant. These
      complications range from bacterial, fungal, and viral pulmonary infections to
      noninfectious conditions such as diffuse alveolar hemorrhage and idiopathic
      pneumonia syndrome. Bronchiolitis obliterans syndrome is the primary chronic
      pulmonary complication, and treatment of this condition remains challenging. This
      report highlights the advances in the diagnosis and management of the major
      pulmonary complications after hematopoietic stem cell transplant. It also
      underscores the need for prospective and multicenter research to have a better
      understanding of the mechanisms behind these complications and to obtain more
      effective diagnostic tool and therapeutic options.

PMID- 27040987
TI  - A novel non-canonical Notch signaling regulates expression of synaptic vesicle
      proteins in excitatory neurons.
AB  - Notch signaling plays crucial roles for cellular differentiation during
      development through gamma-secretase-dependent intramembrane proteolysis followed
      by transcription of target genes. Although recent studies implicate that Notch
      regulates synaptic plasticity or cognitive performance, the molecular mechanism
      how Notch works in mature neurons remains uncertain. Here we demonstrate that a
      novel Notch signaling is involved in expression of synaptic proteins in
      postmitotic neurons. Levels of several synaptic vesicle proteins including
      synaptophysin 1 and VGLUT1 were increased when neurons were cocultured with Notch
      ligands-expressing NIH3T3 cells. Neuron-specific deletion of Notch genes
      decreased these proteins, suggesting that Notch signaling maintains the
      expression of synaptic vesicle proteins in a cell-autonomous manner.
      Unexpectedly, cGMP-dependent protein kinase (PKG) inhibitor, but not gamma
      secretase inhibitor, abolished the elevation of synaptic vesicle proteins,
      suggesting that generation of Notch intracellular domain is dispensable for this
      function. These data uncover a ligand-dependent, but gamma-secretase-independent,
      non-canonical Notch signaling involved in presynaptic protein expression in
      postmitotic neurons. 

PMID- 27040988
TI  - Liberal long-term opioid prescription--more pain than gain?

PMID- 27040990
TI  - Kounis syndrome revisited: Systemic mastocytosis and severe coronary artery
      disease.

PMID- 27040991
TI  - Effect of the alkaline cation size on the conductivity in gel polymer
      electrolytes and their influence on photo electrochemical solar cells.
AB  - The nature and concentration of cationic species in the electrolyte exert a
      profound influence on the efficiency of nanocrystalline dye-sensitized solar
      cells (DSSCs). A series of DSSCs based on gel electrolytes containing five alkali
      iodide salts (LiI, NaI, KI, RbI and CsI) and polyacrylonitrile with plasticizers
      were fabricated and studied, in order to investigate the dependence of solar cell
      performance on the cation size. The ionic conductivity of electrolytes with
      relatively large cations, K(+), Rb(+) and Cs(+), was higher and essentially
      constant, while for the electrolytes containing the two smaller cations, Na(+)
      and Li(+), the conductivity values were lower. The temperature dependence of
      conductivity in this series appears to follow the Vogel-Tamman-Fulcher equation.
      The sample containing the smallest cation shows the lowest conductivity and the
      highest activation energy of ~36.5 meV, while K(+), Rb(+) and Cs(+) containing
      samples show an activation energy of ~30.5 meV. DSSCs based on the gel
      electrolyte and a TiO2 double layer with the N719 dye exhibited an enhancement in
      the open circuit voltage with increasing cation size. This can be attributed to
      the decrease in the recombination rate of electrons and to the conduction band
      shift resulting from cation adsorption by TiO2. The maximum efficiency value,
      3.48%, was obtained for the CsI containing cell. The efficiencies shown in this
      study are lower compared to values reported in the literature, and this can be
      attributed to the use of a single salt and the absence of other additives, since
      the focus of the present study was to analyze the cation effect. The highest
      short circuit current density of 9.43 mA cm(-2) was shown by the RbI containing
      cell. The enhancement of the solar cell performance with increasing size of the
      cation is discussed in terms of the effect of the cations on the TiO2 anode and
      ion transport in the electrolyte. In liquid electrolyte based DSSCs, the short
      circuit current density has been reported to decrease with the increasing size of
      the cation. However, in this work, it follows an opposite trend highlighting a
      major difference between liquid and quasi-solid electrolytes on the solar cell
      performance. 

PMID- 27040994
TI  - Modelling the cost-effectiveness of adopting risk-stratified approaches to
      extended screening intervals in the national diabetic retinopathy screening
      programme in Scotland.
AB  - AIMS: To assess the cost-effectiveness of adopting risk-stratified approaches to
      extended screening intervals in the national diabetic retinopathy screening
      programme in Scotland. METHODS: A continuous-time hidden Markov model was fitted
      to national longitudinal screening data to derive transition probabilities
      between observed non-referable and referable retinopathy states. These were
      incorporated in a decision model simulating progression, costs and visual acuity
      outcomes for a synthetic cohort with a covariate distribution matching that of
      the Scottish diabetic screening population. The cost-effectiveness of adopting
      extended (2-year) screening for groups with no observed retinopathy was then
      assessed over a 30-year time horizon. RESULTS: Individuals with a current grade
      of no retinopathy on two consecutive screening episodes face the lowest risk of
      progressing to referable disease. For the cohort as a whole, the incremental cost
      per quality-adjusted life year gained for annual vs. biennial screening ranged
      from approximately L74 000 (for those with no retinopathy and a prior observed
      grade of mild or observable background retinopathy) to approximately L232 000 per
      quality-adjusted life year gained (for those with no retinopathy on two
      consecutive screening episodes). The corresponding incremental cost-effectiveness
      ratios in the subgroup with Type 1 diabetes were substantially lower;
      approximately L22 000 to L85 000 per quality-adjusted life year gained,
      respectively. CONCLUSIONS: Biennial screening for individuals with diabetes who
      have no retinopathy is likely to deliver significant savings for a very small
      increase in the risk of adverse visual acuity and quality of life outcomes. There
      is greater uncertainty regarding the long-term cost-effectiveness of adopting
      biennial screening in younger people with Type 1 diabetes.

PMID- 27040995
TI  - Crosstalk between adipokines and myokines in fat browning.
AB  - Skeletal muscle is the largest organ determining whole-body insulin sensitivity
      and metabolic homoeostasis. Adaptive changes of skeletal muscle in response to
      physical activity include adjustments in the production and secretion of muscle
      derived bioactive factors, known as myokines, such as myostatin, IL-4, IL-6, IL-7
      and IL-15, myonectin, follistatin-like 1 or leukaemia inhibitory factor. These
      myokines not only act locally in the muscle in an autocrine/paracrine manner, but
      also are released to the bloodstream as endocrine factors to regulate
      physiological processes in other tissues. Irisin, derived from the cleavage of
      FNDC5 protein, constitutes a myokine that induces myogenesis and fat browning
      (switch of white adipocytes to brown fat-like cells) together with a concomitant
      increase in energy expenditure. Besides being a target for irisin actions, the
      adipose tissue also constitutes a production site of FNDC5. Interestingly, irisin
      secretion from subcutaneous and visceral fat depots is decreased by long-term
      exercise training and fasting, suggesting a discordant regulation of FNDC5/irisin
      in skeletal muscle and adipose tissue. Accordingly, our group has recently
      reported that the adipokine leptin differentially regulates FNDC5/irisin
      expression in skeletal muscle and fat, confirming the crosstalk between both
      tissues. Moreover, irisin secretion and function are regulated by other myokines,
      such as follistatin or myostatin, as well as by other adipokines, including
      fibroblast growth factor 21 and leptin. Taken together, myokines have emerged as
      novel molecular mediators of fat browning and their activity can be modulated by
      adipokines, confirming the crosstalk between skeletal muscle and adipose tissue
      to regulate thermogenesis and energy expenditure.

PMID- 27040996
TI  - Information retrieval, critical appraisal and knowledge of evidence-based
      dentistry among Finnish dental students.
AB  - BACKGROUND: One of the core skills of competent dentist is the ability to search
      and analyse high-quality evidence. Problems in understanding the basic aspects of
      knowledge-based information may impede its implementation into clinical practice.
      We examined how Finnish dental students acquire scientific information and how
      familiar they are with methods for evaluating scientific evidence related to
      clinical questions. METHODS: All fifth-year dental students (n = 120) at the
      three universities in Finland received a self-administered questionnaire.
      RESULTS: The three most commonly used sources of information were colleagues, the
      commercial Health Gate Portal for dental practitioners and personal lecture
      notes. Although students rarely read scientific journals, they did find that they
      possess at least passable or even good skills in literature retrieval. Three
      questions related to the appraisal of evidence in dentistry revealed that
      students' knowledge of evidence-based dentistry was inadequate to critically
      evaluate clinical research findings. CONCLUSION: Most students seem to lack
      knowledge of key methodological evidence-based terms. The present curricula in
      dental schools fail to encourage the students to search and acquire knowledge
      wider than their patients themselves do. Universities have the responsibility to
      teach dentists various methods of critical appraisal to cope with scientific
      information.

PMID- 27040997
TI  - Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and
      Literature Review.
AB  - The authors describe the sixth pediatric case to date of primary vulvar melanoma
      associated with lichen sclerosus and propose a practical management for such a
      rare cancer.

PMID- 27040998
TI  - Proteomic profile of platelets during reconstitution of platelet counts after
      apheresis.
AB  - PURPOSE: Circulating platelets consist of subpopulations of different age. We
      designed an approach to remove platelets from circulation using platelet
      apheresis. We aimed to detect changes in the platelet proteome related to
      increased platelet turnover after apheresis to map candidate proteins, which may
      serve as markers of young platelets. EXPERIMENTAL DESIGN: A healthy donor
      underwent three platelet apheresis procedures on three consecutive days. Blood
      was drawn at day 1 (baseline) and at days 3, 5, 7, 9, and 11 for the analysis of
      the platelet proteome using LC-ESI-MS/MS and 2D-DIGE. RESULTS: Among 1017
      proteins identified by LC-ESI-MS/MS, 54 changed in quantity throughout the course
      of the study. Potential markers of young platelets were 40S ribosomal protein SA,
      COP9 signalosome complex subunit 5, and proteins involved in clathrin-mediated
      endocytosis signaling. Among 1036 protein spots observed by 2D-DIGE, 45 spots
      displayed changes in fluorescence intensity. Identified spots contained IQ motif
      containing GTPase activating protein 2, talin, moesin, myosin regulatory light
      chain 2, and coronin-1C. CONCLUSIONS AND CLINICAL RELEVANCE: We provide the proof
      of principle that a combination of platelet apheresis and proteomic approaches
      enables identification of changes in the platelet proteome that are related to
      platelet de novo synthesis.

PMID- 27040999
TI  - Maternal risk factors involved in specific congenital anomalies of the kidney and
      urinary tract: A case-control study.
AB  - BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) comprise
      a heterogeneous group of birth defects with a variety of genetic and nongenetic
      factors suspected of involvement in the etiology. However, little is known about
      risk factors in specific CAKUT phenotypes. Therefore, we studied potential
      maternal risk factors in individual phenotypes within the CAKUT spectrum.
      METHODS: Questionnaire data were collected from parents of 562 children with
      CAKUT and 2139 healthy controls within the AGORA data- and biobank. Potential
      maternal risk factors investigated included folic acid use, overweight and
      obesity, smoking, alcohol consumption, subfertility, and diabetes mellitus. We
      performed logistic regression analyses to assess associations between these
      potential risk factors and CAKUT phenotypes. RESULTS: Increased risks of CAKUT
      were observed for folic acid use and maternal obesity, while fertility treatment
      by in vitro fertilization or intrauterine insemination and diabetes diagnosed
      during pregnancy also seem to be associated with CAKUT. Use of multivitamins
      reduced the risk (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.2-1.0) as
      opposed to use of folic acid supplements only (OR, 1.3; 95% CI, 1.0-1.8). Folic
      acid use was associated with duplex collecting systems (OR, 1.8; 95% CI, 1.0-3.4)
      and vesicoureteral reflux (OR, 1.8; 95% CI, 1.1-2.9) in particular. A relatively
      strong association was observed between diabetes during pregnancy and posterior
      urethral valves (OR, 2.6; 95% CI, 1.1-5.9). CONCLUSION: Use of folic acid only
      seems to be counterproductive for prevention of CAKUT, in contrast to
      multivitamin use. Furthermore, we observed differences in risk factor patterns
      among CAKUT phenotypes, which stress the importance of separate analyses for each
      phenotype. Birth Defects Research (Part A) 106:596-603, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27041000
TI  - Characterization of 47 Cys2 -His2 zinc finger proteins required for the
      development and pathogenicity of the rice blast fungus Magnaporthe oryzae.
AB  - The Cys2 -His2 (C2H2) zinc finger protein family is the second-largest family of
      transcription factors (TFs) in Magnaporthe oryzae, the causal fungus responsible
      for the destructive rice blast disease. However, little is known about the roles
      of most C2H2 TFs in the development and pathogenicity of M. oryzae. The roles of
      47 C2H2 genes in development and pathogenicity were investigated by gene deletion
      in M. oryzae. The TF-dependent genes in mycelia or appressoria were analyzed with
      RNA sequencing and quantitative PCR (qPCR). Forty-four C2H2 genes are involved in
      growth (20 genes), conidiation (28 genes), appressorium formation (four genes)
      and pathogenicity (22 genes) in M. oryzae. Of these, MGG_14931, named as VRF1, is
      required for pathogenicity, specifically controlling appressorium maturation by
      affecting the expression of genes related to appressorial structure and function,
      including melanin biosynthesis, chitin catabolism, lipid metabolism, proteolysis,
      transmembrane transport, and response to oxidative stress; MGG_01776, named as
      VRF2, is required for plant penetration and invasive growth; conidiation-related
      gene CON7 is required for conidial differentiation; and MoCREA, encoding a carbon
      catabolite repression protein, is a novel repressor of lipid catabolism when
      glucose obtainable in M. oryzae. This study provides many insights into the
      regulation of growth, asexual development, appressorium formation, and
      pathogenicity by C2H2 TFs in M. oryzae.

PMID- 27041001
TI  - Molecular imaging of biothiols and in vitro diagnostics based on an organic
      chromophore bearing a terbium hybrid probe.
AB  - In this research, a novel terbium-based luminescent hybrid inorganic/organic
      probe was designed and synthesized. Mesoporous silica nanospheres dispersed in
      water were used as the appropriate host for the covalently linked lanthanide
      containing organic structures. The lanthanide structure was linked to a sulfonate
      ester unit, which, in the presence of biothiols, was cleaved to result in terbium
      emission. The hybrid probe exhibited the capabilities of quantitative
      determination and detection limits for biothiols were presented (36.8 nM for Cys,
      32.5 nM for GSH, and 34.7 nM for Hcy). Evaluation of luminescence changes in cell
      culture demonstrated that this smart probe is cell membrane permeable and
      selectively lights up in the presence of cysteine and glutathione in human
      embryonic kidney cells and human lung adenocarcinoma cells. This variation in the
      presence of biothiols can be controlled by the treatment with N-methylmaleimide.
      The narrow line-like bands and long-lived excited states of this terbium
      luminescent sensor allows the discrimination of scattering signals and
      interfering fluorescence derived from biological tissues.

PMID- 27041002
TI  - Axillary reverse mapping in patients with breast cancer: Is it oncologically
      safe?
AB  - BACKGROUND: Axillary reverse mapping (ARM) is a technique used to identify the
      lymphatics draining the arm. The aim of this study was to examine the prevalence
      and predictors of ARM node metastases in breast cancer patients undergoing an
      axillary lymph node dissection (ALND). METHODS: A total of 87 patients were
      enrolled in this study. Patent V Blue dye was injected in the upper arm for ARM
      node localization. All patients had an ALND with the identified ARM node removed
      and sent separately for histologic analysis. RESULTS: Of 67 (77%) patients in
      whom an ARM node was identified, 49 (73%) were negative and 18 (27%) were
      positive for metastases on final histopathology. Positive ARM node status was
      significantly associated with advanced axillary disease, and larger primary
      cancers. Patients requiring a completion ALND due to a positive sentinel lymph
      node biopsy (SLNB) with non-suspicious ARM nodes during surgery did not have ARM
      node metastases. CONCLUSIONS: There is a high risk of ARM node involvement,
      approximately a quarter, in patients with preoperatively known lymph node
      metastases from breast cancer. However, it may be safe to preserve a clinically
      non-suspicious ARM node in patients with a positive SLNB who require a completion
      ALND. J. Surg. Oncol. 2016;113:726-731. (c) 2016 Wiley Periodicals, Inc.

PMID- 27041003
TI  - Characterization of an experimental resin composite organic matrix based on a tri
      functional methacrylate monomer.
AB  - This study evaluated the potential of a tri-functional monomer
      (trimethylolpropane trimethacrylate -TMPTMA) for inclusion in a dental composite
      organic matrix. Initially, four ternary matrixes with different concentrations
      (wt%) of bi-functional monomers [BisGMA (G), Bis-EMA (E) and TEGDMA (T)] were
      analyzed: GET523, GET532, EGT523 and EGT532 (the numbers (n) represent n*10 wt%
      of each monomer). The following properties were evaluated: degree of conversion,
      flexural strength, elastic modulus, hardness, absorption, solubility, diffusion
      coefficient of water and crosslink density. Based on the best overall results
      obtained for EGT532, all properties were re-evaluated in a matrix where TEGDMA
      (T) was replaced by a tri-functional monomer, TMPTMA (A)-EGA532. EGA532 presented
      the best results for flexural strength, hardness, absorption and crosslink
      density. EGT523, EGT532 and EGA532 presented the lowest diffusion coefficients of
      water. The overall results indicated that TMPTMA could be useful in formulating
      organic matrixes suitable for dental restorative composites. 

PMID- 27041004
TI  - Evaluation of microtensile bond strength of self-etching adhesives on normal and
      caries-affected dentin.
AB  - The purpose of this study was to evaluate the uTBS (microtensile bond strength)
      of currently available self-etching adhesives with an experimental self-etch
      adhesive in normal and caries-affected dentin, using a portable hardness
      measuring device, in order to standardize dentin Knoop hardness. Normal (ND) and
      caries-affected dentin (CAD) were obtained from twenty human molars with class II
      natural caries. The following adhesive systems were tested: Mega Bond (MB), a 2
      step self-etching adhesive; MTB-200 (MTB), an experimental 1-step self-etching
      adhesive (1-SEA), and two commercially available one-step self-etching systems, G
      Bond Plus (GB) and Adper Easy Bond (EB). MB-ND achieved the highest uTBS
      (p<0.05). The mean uTBS was statistically lower in CAD than in ND for all
      adhesives tested (p<0.05), and the 2-step self-etch adhesive achieved better
      overall performance than the 1-step self-etch adhesives. 

PMID- 27041005
TI  - Self-etch or etch-and-rinse mode did not affect the microshear bond strength of a
      universal adhesive to primary dentin.
AB  - This study evaluated the microshear bond strength (uSBS) of resin composite to
      primary dentin using a universal adhesive in etchand-rinse mode or self-etch
      mode. Flat ground dentin surfaces were created on forty extracted human primary
      incisors and randomly assigned into four groups (n=10): Adper Single Bond II
      (ASB), Clearfil SE Bond (CSE), Single Bond Universal etch-and-rinse (SBUER) and
      Single Bond Universal self-etch (SBU-SE). Adhesive was applied on the dentin
      surface, which was subsequently bonded with a resin composite. The uSBS test was
      performed using a universal testing machine at a crosshead speed of 1 mm/min. The
      ASB group generated a lower mean uSBS (19.1+/-3.4 MPa) than those of the other
      groups [SBU-ER (24.3+/-2.7 MPa), SBU-SE (25.1+/-2.4 MPa), and CSE (25.3+/-2.7
      MPa)]. Adhesive failure was the most common failure mode in each group. In
      conclusion, SBU used in etch-and-rinse or self-etch mode resulted in similar bond
      strength to primary dentin. 

PMID- 27041006
TI  - Three-dimensional finite element analysis of stress distribution in inlay
      restored mandibular first molar under simultaneous thermomechanical loads.
AB  - Functional occlusal loads and intraoral temperature changes create stress in
      teeth. The purpose of this study was to evaluate the impact of simultaneous
      thermomechanical loads on stress distribution related to inlay restored teeth by
      three-dimensional finite element analysis. A mandibular first molar was
      constructed with tooth structures, surrounding bone and inlays of Type II gold
      alloy, ceramic, and composite resin. Stress patterns on the restorative
      materials, adhesive resin, enamel and dentin were analyzed after simulated
      temperature changes from 36 degrees C to 4 or 60 degrees C for 2 s with 200-N
      oblique loading. The results showed that the three types of inlays had similar
      stress distribution in the tooth structures and restorative materials. Concerning
      the adhesive resin, the composite resin inlay model exhibited lower stresses than
      ceramic and gold alloy inlays. Simultaneous thermomechanical loads caused high
      stress patterns in inlay-restored teeth. Composite resin inlays may be the better
      choice to avoid adhesive failure. 

PMID- 27041007
TI  - The influences of accelerated aging on mechanical properties of veneering
      ceramics used for zirconia restorations.
AB  - This study evaluated the influences of accelerated aging on the mechanical
      properties of veneering ceramics used for zirconia frameworks. Five different
      veneering ceramics for zirconia frameworks were used. Twenty specimens were
      fabricated for each veneering ceramic. All specimens were divided into two
      groups. One was subjected to accelerated aging and the other was used as a
      control. Accelerated aging was performed in distilled water for 5 h at 200oC and
      2 atm. The density, open porosity, surface roughness, three-point flexural
      strength, and Vickers hardness were measured. The results showed that the
      density, open porosity, and surface roughness of all examined veneering ceramics
      were changed by the accelerated aging process. Accelerated aging was also found
      to have a positive effect on strength and a negative effect on the hardness. 

PMID- 27041008
TI  - Peel bond strength of soft lining materials with antifungal to a denture base
      acrylic resin.
AB  - The effect of the addition of nystatin, miconazole, ketoconazole, chlorhexidine,
      and itraconazole into the soft lining materials Softone and Trusoft on their peel
      bond strength to a denture base acrylic resin was evaluated. Specimens of soft
      lining materials (n=7) were made without (control) or with the incorporation of
      antifungals at their minimum inhibitory concentrations to the biofilm of C.
      albicans and bonded to the acrylic resin. Peel testing was performed after
      immersion in distilled water at 37oC for 24 h, 7 and 14 days. Data (MPa) were
      analyzed by 3-way ANOVA/Tukey-Kramer test (alpha=0.05) and the failure modes were
      classified. The addition of nystatin and ketoconazole did not affect the peel
      bond strength for up to 14 days. Most failures were predominantly cohesive within
      soft lining materials. With the exception of itraconazole, incorporating the
      antifungals into the soft lining materials did not result in values below those
      recommended for peel bond strength after 7 and 14 days of analysis. 

PMID- 27041009
TI  - Effect of long-term water immersion or thermal shock on mechanical properties of
      high-impact acrylic denture base resins.
AB  - The purpose of this study was to investigate the effect of long-term water
      immersion or thermal shock on the mechanical properties of high-impact acrylic
      denture base resins. Two high-impact acrylic denture base resins were selected
      for the study. Specimens of each denture base material tested were fabricated
      according to the manufacturers' instructions (n=10). The flexural strength at the
      proportional limit, the elastic modulus and the impact strength of the specimens
      were evaluated. The flexural strength at the proportional limit of the high
      impact acrylic denture base resins did not change after six months' water
      immersion or thermocycling 50,000 times. The elastic moduli of the high-impact
      acrylic denture base resins significantly increased after six months' water
      immersion or thermocycling 50,000 times. The impact strengths of the high-impact
      acrylic denture base resins significantly decreased after water immersion or
      thermocycling as described above. 

PMID- 27041010
TI  - Effects of temperature-responsive hydrogel on viscosity of denture adhesives.
AB  - The cream type of denture adhesives after use cannot be easily removed from oral
      mucosa and have the potential risk to change the oral flora. The effects of the
      temperature-responsive hydrogel Pluronic F-127 (PF) on the complex viscosity of
      denture adhesives were evaluated. Carboxy methylcellulose (CMC) mass fractions
      (1, 2, 3 and 4%) were added to 20 and 25% PF hydrogels. Complex viscosity was
      measured over a temperature cycle (40->10->40 degrees C) and fixed temperature
      points (23 and 37 degrees C). Adhesive strength tests were performed with 2 resin
      plates at 23 and 37 degrees C. One commercial cream-type denture adhesive, New
      Poligrip(r) (NP), was evaluated as a control. Complex viscosity values for PF20%
      groups at 23 degrees C were lower than those for NP at 37 degrees C. Adhesive
      strength of PF20% with CMC2%, was higher at 23 degrees C when compared to NP at
      37 degrees C, which suggests that PF20%CMC2% is an effective adhesive and is
      easily removed after mouth rinsing.

PMID- 27041011
TI  - Comparative study on the resorbability and dissolution behavior of octacalcium
      phosphate, beta-tricalcium phosphate, and hydroxyapatite under physiological
      conditions.
AB  - The dissolution behaviors of octacalcium phosphate (OCP), beta-tricalcium
      phosphate (beta-TCP), and hydroxyapatite (HA) were compared by implanting the
      materials in rat subcutaneous pouches for 8 weeks using a filter chamber or
      immersing them in simulated body fluid (SBF) or Tris-HCl buffer for 2 weeks at pH
      7.4 and 37(o)C. X-ray diffraction, Fourier transform infrared spectroscopy,
      scanning electron microscopy, and chemical analysis were conducted on these
      materials. Degree of supersaturation (DS) in the two solutions immersed with each
      calcium phosphate material was calculated from their chemical compositions. The
      results showed that OCP partially converted to apatitic crystals, while beta-TCP
      and HA remained unchanged after the implantation. The DS of the SBF solution
      remained slightly supersaturated with respect to OCP and beta-TCP, but slightly
      undersaturated in the Tris-HCl buffer. These findings suggest that previously
      reported OCP and beta-TCP biodegradation could be induced through cell-mediated
      osteoclastic resorption rather than a simple dissolution process. 

PMID- 27041012
TI  - Toothbrushing alters the surface roughness and gloss of composite resin CAD/CAM
      blocks.
AB  - This study investigated the surface roughness and gloss of composite resin
      CAD/CAM blocks after toothbrushing. Five composite resin blocks (Block HC,
      Cerasmart, Gradia Block, KZR-CAD Hybrid Resin Block, and Lava Ultimate), one
      hybrid ceramic (Vita Enamic), one feldspar ceramic (Vitablocs Mark II), one PMMA
      block (Telio CAD), and one conventional composite resin (Filtek Z350 XT) were
      evaluated. Surface roughness (Ra) and gloss were determined for each group of
      materials (n=6) after silicon carbide paper (P4000) grinding, 10k, 20k, and 40k
      toothbrushing cycles. One-way repeated measures ANOVA indicated significant
      differences in the Ra and gloss of each material except for the Ra of GRA. After
      40k toothbrushing cycles, the Ra of BLO and TEL showed significant increases,
      while CER, KZR, ULT, and Z350 showed significant decreases. GRA, ENA, and VIT
      maintained their Ra. All of the materials tested, except CER, demonstrated
      significant decreases in gloss after 40k toothbrushing cycles. 

PMID- 27041013
TI  - Mechanical resistance evaluation of a novel anatomical short glass fiber
      reinforced post in artificial endodontically treated premolar under
      rotational/lateral fracture fatigue testing.
AB  - This study develops a novel anatomical short glass fiber reinforced (anatomical
      SGFR) post and evaluates the mechanical performance in artificial endodontically
      treated premolars. An anatomical SGFR fiber post with an oval shape and
      slot/notch designs was manufactured using an injection-molding machine. The three
      point bending test and crown/core restorations using the anatomical SGFR and
      commercial cylindrical fiber posts under fatigue test were executed to understand
      the mechanical resistances. The results showed that static and dynamic rotational
      resistance were found significantly higher in the anatomical SGFR fiber post than
      in the commercial post. The endurance limitations at 1.2*10(6) cycles were 66.81
      and 64.77 N for the anatomical SGFR and commercial fiber posts, respectively. The
      anatomical SGFR fiber post presented acceptable value of flexural strength and
      modulus, better fit adaption in the root canal resist torque more efficiency but
      was not a key issue in the lateral fracture resistance in an endodontically
      treated premolar. 

PMID- 27041014
TI  - A promising scaffold with excellent cytocompatibility and pro-angiogenesis action
      for dental tissue engineering: Strontium-doped calcium polyphosphate.
AB  - Angiogenesis is of great importance in dental tissue engineering. Therefore, it
      is quite necessary for dental tissue engineering to develop a new scaffold with
      bioactivity to induce angiogenesis. This study was performed to determine the
      ability of 1% strontium-doped calcium polyphosphate (SCPP) to induce angiogenesis
      by detecting the levels of VEGF and bFGF from cultured human dental pulp cells
      (hDPCs). Results of scanning electron microscopy (SEM) and confocal laser
      scanning microscopy (CLSM) tests indicated the growth of hDPCs on 1%SCPP
      scaffolds was more superior than that on calcium polyphosphate (CPP) and
      hydroxyapatite (HA) scaffolds. The detection of MTT indicated 1%SCPP could
      accelerate proliferation of hDPCs. Further analyzed with ELISA demonstrated the
      protein levels of VEGF, bFGF from cultured hDPCs on 1%SCPP scaffolds were
      significantly higher than that on CPP and HA scaffolds. These findings above
      suggested 1%SCPP could be a promising scaffold for dental tissue engineering to
      induce angiogenesis.

PMID- 27041015
TI  - Dimensional accuracy of dental casting patterns created by 3D printers.
AB  - Contrary to widespread incise CAD/CAM, little is known about the dental
      application of 3D printing, especially the possibility of using 3D printing with
      organic material. The resin patterns of a full crown model were created by four
      types of 3D printers, a thermofusion device (CX), a digital light processing
      stereo-lithograph device (B9), a laser stereo-lithograph device (DW) and a multi
      jet modeling device (PJ). The dimensional accuracy of the outer and inner
      diameters and depths of the created model crowns, and the surface roughness of
      sidewall were investigated. The outer diameters were smaller than the designed
      value in most conditions. The inner diameters were smaller than the designed
      value in any enlargement ratio except B9. The depth of CX or B9 tended to become
      shallower, though that of PJ or DW tended to increase. The surface roughness
      along the tooth axis direction was greater than that perpendicular to the tooth
      axis. 

PMID- 27041016
TI  - Comparative radiopacity of conventional and full-contour Y-TZP ceramics.
AB  - The purpose of this study was to evaluate the radiopacity of different yttria
      stabilized tetragonal zirconia polycrystalline (Y-TZP) ceramics used in the
      fabrication of fixed dental prostheses. Disk-shaped specimens (N=120, n=30 per
      group) were fabricated with thicknesses of 0.3, 0.5, and 1 mm from the following
      four Y-TZP ceramics: Cercon ht (Degudent) (CZ), Prettau (Zirkonzahn) (ZZ),
      Alliance (Kuraray Noritake Dental) (NA), and Ice Zirkon (Zirkonzahn) (ICE). The
      optical densities of each material were measured from radiographic images, and
      each material (N=1) were characterized by using XRD and SEM. The results were
      analyzed with oneway analysis of variance and the Tukey-Kramer test (alpha=0.05).
      In the case of the ICE and NA specimens, the radiopacity significantly differed
      with thickness (p<0.05). However, the radiopacities of 0.5- and 0.3-mm-thick CZ
      and ZZ specimens were not significantly different (p>0.05). Full-contour Y-TZP
      materials have higher radiopacities than those of the conventional Y-TZP
      materials in decreased thicknesses. 

PMID- 27041017
TI  - In vitro evaluation of the flexural properties of All-on-Four provisional fixed
      denture base resin partially reinforced with fibers.
AB  - The aim of this study was to assess the effects of partial carbon or glass fiber
      reinforcement on the flexural properties of All-on-Four provisional fixed denture
      base resin. The carbon or glass fibers were woven (3% by weight) together in
      three strands and twisted and tightened between the two abutments in a figure-of
      "8" pattern. Four types of specimens were fabricated for the three-point loading
      test. The interface between the denture base resin and fibers was examined using
      scanning electron microscopy (SEM). Reinforcement with carbon or glass fibers
      between two abutments significantly increased the flexural strength and flexural
      modulus. SEM revealed relatively continuous contact between the fibers and
      acrylic resin. The addition of carbon or glass fibers between two abutments
      placed on All-on-Four provisional fixed denture base resin may be clinically
      effective in preventing All-on-Four denture fracture and can provide several
      advantages for clinical use. 

PMID- 27041018
TI  - Application of neutral electrolyzed water to disinfection of alginate impression.
AB  - Neutral electrolyzed water was developed with new concepts of long-term good
      durability and minimum corrosiveness to metal in addition to its excellent
      bactericidal activities similar to acid type of electrolyzed waters. The present
      study examined the bactericidal effects of the neutral electrolyzed water on
      disinfection of the alginate impression of a dental arch model contaminated by
      bacteria. Only 1-min immersion in neutral electrolyzed water could sufficiently
      disinfect the alginate impression including the metallic tray under ultrasonic
      with no significant differences from acid electrolyzed waters. No bactericidal
      effects were found in any electrolyzed water when used as mixing water.
      Considering the advantages and disadvantages of each electrolyzed water in a
      comprehensive way, it was suggested that neutral electrolyzed water may be the
      most appropriate for the disinfection of alginate impression. 

PMID- 27041019
TI  - Evaluation of the surface hardness, roughness, gloss and color of composites
      after different finishing/polishing treatments and thermocycling using a
      multitechnique approach.
AB  - The objectives of this study were to evaluate the mechanical and physical
      properties of resin composites. The materials evaluated were the Clearfil Majesty
      Posterior, Filtek Z550 and G-aenial Posterior composites. A total of 189
      specimens were fabricated for microhardness, roughness, gloss and color tests.
      The specimens were divided into three finishing and polishing systems: Enhance,
      OneGloss and Sof-Lex Spiral. Microhardness, roughness, gloss and color were
      measured after 24 h and after 10,000 thermocycles. Two samples from each group
      were evaluated using SEM and AFM. G-aenial Posterior exhibited the lowest
      microhardness values. The mean roughness ranged from 0.37 to 0.61 um. The
      smoothest surfaces were obtained with Sof-Lex Spiral for each material. G-aenial
      Posterior with Enhance was determined to be the glossiest surfaces. All of the
      materials exhibited similar DeltaE values ranging between 1.69 and 2.75. Sof-Lex
      Spiral discs could be used successfully to polish composites. 

PMID- 27041020
TI  - Fabrication of all-ceramic crowns by a new method.
AB  - A new method of all-ceramic production using alumina coping has been developed.
      The present study investigates the influence of secondary firing (glass
      infiltration firing) conditions. Samples of porcelain build-up without secondary
      firing were also assessed. The suitability of coping that included secondary
      firing was found to be affected by the rate of temperature increase during the
      secondary firing. However, cracking developed in the fired porcelain if porcelain
      was built up onto secondarily-fired coping. In contrast, cracking did not occur
      with coping that was not secondarily fired. The bending strength after porcelain
      build-up was 70 MPa or higher, suggesting the possibility of clinical
      applications as an anterior crown. These findings establish that this is method
      of producing all-ceramic crowns that allows for low-cost manufacture in a short
      period of about 1 h.

PMID- 27041021
TI  - Effect of activation modes on the compressive strength, diametral tensile
      strength and microhardness of dual-cured self-adhesive resin cements.
AB  - The purpose of this study was to compare the compressive strength, diametral
      tensile strength and microhardnss of several selfadhesive resin cements (Rely-X
      U200, Clearfill SA Luting, G-CEM LinkAce, Maxcem Elite, PermaCem 2.0, and
      Zirconite) using different activation modes (self-cured, light-cured) and testing
      time (immediately, 24 h, thermocycling). Specimens were prepared for the
      compressive strength (O 4*6 mm) and diametral tensile strength and microhardness
      (O 6*3 mm) according to ISO standards. The strength after 24 h was higher than
      immediately after. In addition, G-CEM showed the highest values. In terms of the
      activation modes, Rely-X U200, PermaCem 2.0 had higher values in the light-curing
      than the self-curing. In conclusion, all cements demonstrated clinically
      available strength values and revealed differences in strength according to their
      composition, testing time and activation mode. Furthermore, correlation was found
      between the microhardness (degree of conversion) and mechanical strengths of the
      cements tested. 

PMID- 27041022
TI  - Hardening by cooling rate control and post-firing heat treatment in Pd-Ag-Sn
      alloy for bonding porcelain.
AB  - The aim of this study was to determine the hardening effect by controlling the
      cooling rate during the porcelain firing process and performing an additional
      post-firing heat treatment in a Pd-Ag-Sn alloy. The most effective cooling rate
      for alloy hardening was determined by cooling the specimens at various cooling
      rates after oxidation treatment. A subsequent porcelain firing simulation
      followed by cooling at the selected cooling rate was performed. A post-firing
      heat treatment was then done at 600 degrees C in a porcelain furnace. The
      hardening mechanism was characterized by a hardness test, X-ray diffraction,
      field emission scanning electron microscopy and energy dispersive X-ray
      spectroscopy. Alloy softening occurred during the porcelain firing process
      followed by cooling at a controlled cooling rate. A post-firing heat treatment
      allowed apparent precipitation hardening. It is advisable to perform a postfiring
      heat treatment at 600 degrees C in a porcelain furnace by annealing metal
      substructure after porcelain fusing. 

PMID- 27041023
TI  - Assessment of the inhibitory effects of fissure sealants on the demineralization
      of primary teeth using an automatic pH-cycling system.
AB  - In this study, we examined the effects of fissure sealants on inhibition of
      demineralization of primary teeth using an automatic pHcycling system. Three
      fissure sealants were used: Teethmate F-1 2.0 (TM), BeautiSealant (BS), and Fuji
      III LC (IIILC). Using an automatic pH-cycling system, the specimens (n=12) were
      repeatedly demineralized and remineralized. Specimens were subjected to
      transverse microradiography (TMR), and changes in integrated mineral loss (IML)
      and lesion depth (Ld), indicated as DeltaIML and DeltaLd, respectively, were
      calculated. In addition, fluoride levels in the enamel were assessed using
      microparticle-induced gamma-ray emission/particle-induced X-ray emission (n=3).
      IIILC showed the lowest values for DeltaIML and DeltaLd, followed by BS and then
      TM. The highest amount of fluorine in the enamel was observed for IIILC, followed
      by TM and BS. All fissure sealants inhibited demineralization in primary teeth.

PMID- 27041024
TI  - Effects of silica-coating on surface topography and bond strength of porcelain
      fused to CAD/CAM pure titanium.
AB  - The aim of this study was to evaluate the shear bond strength of porcelain fusing
      to titanium and the effects of surface treatment on surface structure of
      titanium. In the shear bond strength test, titanium surface treatments were:
      conventional, silica-coating without bonding agent, and silica-coating with
      bonding agent. Titanium surface treatments for analysis by the atomic force
      microscope (AFM) were: polishing, alumina sandblasting and silica-coating. The
      shear bond strength value of silica-coating with bonding agent group showed
      significantly higher than that of other groups. In AFM observation results,
      regular foamy structure which is effective for wetting was only observed in
      silica-coating. Therefore, this structure might indicate silicon. Silica-coating
      renders forms a nanoscopic regular foamy structure, involved in
      superhydrophilicity, to titanium surface, which is markedly different from the
      irregular surface generated by alumina sandblasting. 

PMID- 27041025
TI  - Erratum to: Effect of resin infiltration on enamel surface properties and
      Streptococcus mutans adhesion to artificial enamel lesions.
AB  - Authors would like to add ACKNOWLEGMENT in this article, page 30, between
      CONCLUSION and REFERENCES as below. ACKNOWLEGMENT: This research was supported by
      Erciyes University Scientific Research Project Department.

PMID- 27041026
TI  - Erratum to: Effects of metal- and fiber-reinforced composite root canal posts on
      flexural properties.
AB  - Erratum to: Dental Materials Journal 2016; 35(1): 138-146. doi:10.4012/dmj.2015
      193 JOI JST.JSTAGE/dmj/2015-193. Figure 1, 2 and 3 (a) should be corrected as
      below.

PMID- 27041027
TI  - Nondominant small follicles are a promising source of mature oocytes in modified
      natural cycle in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To determine whether oocyte retrieval from nondominant small follicles
      supplies mature oocytes and increases live births in natural cycle IVF and embryo
      transfer (IVF-ET). DESIGN: Retrospective cohort study. SETTING: Private assisted
      reproductive technology practice. PATIENT(S): Seven hundred seventy-one infertile
      women who underwent natural cycle IVF between 2011 and 2013. INTERVENTION(S): The
      LH surge was triggered via nasal buserelin when the dominant follicle reached 16
      18 mm during nonstimulated cycles, and as many oocytes as possible were retrieved
      from nondominant small follicles (a diameter of 3-10 mm) after retrieval from the
      large (dominant) follicle. The embryos were cryopreserved once they had yielded
      good-quality blastocysts and then transferred (one per cycle) during subsequent
      cycles. MAIN OUTCOME MEASURE(S): Number of mature oocytes (metaphase II) and
      resulting live births yielded via oocyte retrieval from the initial cycle of
      treatment. RESULT(S): Among 771 women, nondominant small follicle puncture
      yielded 902 metaphase II oocytes and 78 live births, whereas large dominant
      follicle puncture yielded 466 metaphase II oocytes and 90 live births. Successes
      in oocyte retrieval and live births resulting from small follicle puncture were
      positively correlated with ovarian reserve but did not depend on the outcomes of
      the dominant follicle puncture. CONCLUSION(S): Nondominant small follicles are a
      promising supplementary source of mature oocytes for natural cycle IVF.

PMID- 27041029
TI  - MESSAGE FROM THE EDITOR: PUBLICATION OF PAPERS FROM THE SYMPOSIUM "BORROWED
      CHLOROPLASTS: SECONDARY ENDOSYMBIOSIS AND THE CHROMALVEOLATES".

PMID- 27041028
TI  - Syndecan-4 expression is upregulated in endometriosis and contributes to an
      invasive phenotype.
AB  - OBJECTIVE: To study the expression and function of syndecan-4 in endometriosis.
      DESIGN: Histopathological investigation of eutopic endometrium and experimental
      laboratory study on a cell line derived from epithelial endometriotic cells
      (12Z). SETTING: University hospital laboratory. PATIENT(S): One hundred six women
      (62 controls/44 endometriosis) from the IVF center of Munster University Hospital
      aged 23-44 undergoing Pipelle biopsy and diagnostic exploratory laparoscopy.
      INTERVENTION(S): Eutopic endometrial tissue was investigated by
      immunohistochemistry for the expression of syndecan-4. The human endometriotic
      cell line 12Z was transiently transfected with syndecan-4 small interfering RNA
      and investigated for changes in cell behavior. MAIN OUTCOME MEASURE(S): Syndecan
      4 expression in eutopic endometrium was evaluated immunohistochemically in
      endometrial glands and stroma. Scoring results were correlated with the stages of
      the menstrual cycle and presence or absence of endometriosis. Quantitative
      polymerase chain reaction was used to measure syndecan-4-dependent expression
      changes of MMP2, MMP3, MMP9, Rac1, and ATF2. Altered cell behavior was monitored
      by matrigel invasion assays and cell viability assays. RESULT(S): Syndecan-4
      expression was significantly higher in the glands and stroma of patients with
      endometriosis compared with controls, whereas no menstrual cycle-dependent
      expression was observed. In 12Z cells, syndecan-4 depletion did not affect cell
      viability but resulted in a significantly reduced matrigel invasiveness and
      reduced expression of the small GTPase Rac1, the transcription factor ATF-2, and
      MMP3. CONCLUSION(S): The upregulation of syndecan-4 in the eutopic endometrium of
      endometriosis patients may facilitate the pathogenetic process by promoting
      invasive cell growth via Rac1, MMP3, and ATF-2.

PMID- 27041030
TI  - PSA ANNUAL MEETING 2008.

PMID- 27041031
TI  - PHYLOGENOMICS AND SECONDARY PLASTIDS: A LOOK BACK AND A LOOK AHEAD(1).
AB  - Despite their importance to evolution, ecology, and cell biology, eukaryotes that
      acquired plastids through secondary endosymbiosis remain poorly studied from a
      genomic standpoint. Chromalveolata, a eukaryotic supergroup proposed to have
      descended from a heterotrophic eukaryote that acquired a red algal plastid by
      secondary endosymbiosis, includes four major lineages (alveolates, cryptophytes,
      haptophytes, and heterokonts). The chromalveolates exhibit remarkable diversity
      of cellular organization, and the available data suggest that they exhibit equal
      diversity in their genome organization. One of the most obvious differences in
      cellular organization is the retention of a highly reduced red algal nucleus in
      cryptophytes (also known as cryptomonads), but there are other major differences
      among chromalveolate lineages, including the loss of photosynthesis in multiple
      lineages. Although the hypothesis of chromalveolate monophyly is appealing, there
      is limited support for the hypothesis from nuclear genes, and questions have even
      been raised about the monophyly of chromalveolate plastids. Evidence for the
      chromalveolate hypothesis from large-scale nuclear data sets is reviewed, and
      alternative hypotheses are described. The potential for integrating information
      from chromalveolate genomics into functional genomics is described, emphasizing
      both the methodological challenges and the opportunities for future phylogenomic
      analyses of these groups. 

PMID- 27041032
TI  - ENDOSYMBIOTIC AND HORIZONTAL GENE TRANSFER IN CHROMALVEOLATES(1).
AB  - Chromalveolates include photosynthetic and nonphotosynthetic (some plastid
      lacking) algae and protists that define a vast swath of eukaryotic diversity.
      These taxa are masters of gene acquisition through serial endosymbiosis
      (endosymbiotic gene transfer, EGT) and horizontal gene transfer (HGT).
      Understanding the contribution of these sources to nuclear genomes is key to
      elucidating chromalveolate evolution and to identifying suitable phylogenetic
      markers to place this lineage in the tree of life. Here we briefly review recent
      findings in our lab with regard to EGT and HGT in chromalveolates. 

PMID- 27041033
TI  - NUCLEOMORPH KARYOTYPE DIVERSITY IN THE FRESHWATER CRYPTOPHYTE GENUS
      CRYPTOMONAS(1).
AB  - Cryptophytes are unicellular, biflagellate algae with plastids (chloroplasts)
      derived from the uptake of a red algal endosymbiont. These organisms are unusual
      in that the nucleus of the engulfed red alga persists in a highly reduced form
      called a nucleomorph. Nucleomorph genomes are remarkable in their small size
      (<1,000 kilobase pairs [kbp]) and high degree of compaction (~1 kbp per gene).
      Here, we investigated the molecular and karyotypic diversity of nucleomorph
      genomes in members of the genus Cryptomonas. 18S rDNA genes were amplified,
      sequenced, and analyzed from C. tetrapyrenoidosa Skuja CCAP979/63, C. erosa
      Ehrenb. emmend. Hoef-Emden CCAP979/67, Cryptomonas sp. CCAP979/52, C. lundii Hoef
      Emden et Melkonian CCAP979/69, and C. lucens Skuja CCAP979/35 in the context of a
      large set of publicly available nucleomorph 18S rDNA sequences. Pulsed-field gel
      electrophoresis (PFGE) was used to examine the nucleomorph genome karyotype of
      each of these strains. Individual chromosomes ranged from ~160 to 280 kbp in
      size, with total genome sizes estimated to be ~600-655 kbp. Unexpectedly, the
      nucleomorph karyotype of Cryptomonas sp. CCAP979/52 is significantly different
      from that of C. tetrapyrenoidosa and C. lucens, despite the fact that their 18S
      rDNA genes are >99% identical to one another. These results suggest that
      nucleomorph karyotype similarity is not a reliable indicator of evolutionary
      affinity and provides a starting point for further investigation of the fine
      scale dynamics of nucleomorph genome evolution within members of the genus
      Cryptomonas. 

PMID- 27041034
TI  - GENOMIC INSIGHTS INTO EVOLUTIONARY RELATIONSHIPS AMONG HETEROKONT LINEAGES
      EMPHASIZING THE PHAEOPHYCEAE(1).
AB  - Heterokonts comprise a large and diverse group of organisms unified by the
      heterokont biflagellate condition. Monophyly of many of these lineages is well
      established, but evolutionary relationships among the various lineages remain
      elusive. Among these lineages, the brown algae (Phaeophyceae) are a monophyletic,
      taxonomically diverse, and ecologically critical group common to marine
      environments. Despite their biological and scientific importance, consensus
      regarding brown algal phylogeny and taxonomic relationships is missing. Our long
      term research goal is to produce a well-resolved taxon-rich phylogeny of the
      class to assess evolutionary patterns and taxonomic relationships among brown
      algal lineages and their relationship to other closely related heterokont groups.
      To accomplish this goal and augment existing loci for phaeophycean-wide
      systematic studies, we generated expressed sequence tags (ESTs) from several
      major brown algal lineages and from the heterokont lineage representing the
      closest sister group to brown algae. To date, we have successfully constructed
      cDNA libraries for two lineages (Choristocarpus tenellus Zanardini and
      Schizocladia ischiensis E. C. Henry, Okuda et H. Kawai) and in the library test
      phase obtained up to 1,600 ESTs per organism. Annotation results showed a gene
      discovery rate of 45%-50% for each library revealing 500-700 unique genes from
      each organism. We have identified several potential genes for phylogenetic
      inference and used these loci for preliminary molecular clock analyses. Our
      molecular clock analysis suggests that the basal divergence in brown algae
      occurred around the time of the pennate-centric diatom divergence. Here we report
      this analysis and other uses of ESTs in brown algal phylogenomics and the utility
      of these data for resolving the phylogeny of this group. 

PMID- 27041035
TI  - DETECTING EVOLUTIONARY TRANSFER OF GENES USING PhIGs(1).
AB  - Organisms have acquired plastids by convoluted paths that have provided multiple
      opportunities for gene transfer into a host nucleus from intracellular organisms,
      including the cyanobacterial ancestor of plastids, the proteobacterial ancestor
      of mitochondria, and both green and red algae whose engulfment has led to
      secondary acquisition of plastids. These gene movements are most accurately
      demonstrated by building phylogenetic trees that identify the evolutionary origin
      of each gene, and one effective tool for this is "PhIGs" (Phylogenetically
      Inferred Groups; http://PhIGs.org), a set of databases and computer tools with a
      Web interface for whole-genome evolutionary analysis. PhIGs takes as input gene
      sets of completely sequenced genomes, builds clusters of genes using a novel,
      graph-based approach, and reconstructs the evolutionary relationships among all
      gene families. The user can view and download the sequence alignments, compare
      intron-exon structures, and follow links to functional genomic databases.
      Currently, PhIGs contains 652,756 genes from 45 genomes grouped into 61,059 gene
      families. Graphical displays show the relative positions of these genes among
      genomes. PhIGs has been used to detect the evolutionary transfer of hundreds of
      genes from cyanobacteria and red algae into oomycete nuclear genomes, revealing
      that even though they have no plastids, their ancestors did, having secondarily
      acquired them from an intracellular red alga. A great number of genomes are soon
      to become available that are relevant to our broader understanding of the
      movement of genes among intracellular compartments after engulfing other
      organisms, and PhIGs will be an effective tool to interpret these gene movements.

PMID- 27041036
TI  - ARIADNE'S THREAD: GUIDING A PROTEIN ACROSS FIVE MEMBRANES IN CRYPTOPHYTES(1).
AB  - Cryptophytes are the most archetypal chromalveolates, with their complex plastid
      having retained many features of the red algal secondary endosymbiont. Most
      important of these is the remnant nucleus, the nucleomorph, that is kept between
      the inner and outer membrane pair of the endosymbiont in the highly reduced
      cytosol, the periplastidial compartment (PPC). Because the nucleomorph's coding
      capacity is very limited, proteins need to be imported from the host cytosol
      across the outer two membranes into the PPC and across all four membranes into
      the stroma. How this is accomplished has puzzled researchers for >20 years.
      Recent findings show that in both cases, a bipartite topogenic signal, a signal
      and subsequent transit peptide (TP), is responsible for targeting proteins
      correctly into these two compartments. An aromatic amino acid-based motif at the
      +1 position of the TP holds the information determining into which compartment
      the precursor protein is finally transported. Together with the identification of
      a novel endoplasmic reticulum associated degradation (ERAD)-derived translocon in
      the second-outermost membrane, these findings help us to understand the
      sophisticated targeting mechanisms across four membranes and clarify a key
      innovation during chromalveolate evolution. 

PMID- 27041037
TI  - MICROALGAL BIOTRANSFORMATION OF STEROIDS(1).
AB  - Microbial biotransformation of steroids is not a new concept, but most studies in
      this field have focused on fungal and bacterial systems. Microalgae, despite
      their photosynthetic ability and immense biodiversity, have not received much
      attention in this aspect until recently. Since the publication of the first
      article on microalgal biotransformation of steroids about 20 years ago, there
      have been many reports describing different modifications, including
      hydroxylation, reduction, side-chain degradation, and isomerization introduced by
      these microorganisms on estrane, androstane, and pregnane derivatives. On the
      other hand, the development of new large-scale cultivation systems, the
      adaptation of existing fermentation techniques to microalgae, and the
      introduction of microalgal genetic manipulation methods have made these organisms
      promising candidates for a wide range of biotechnological processes, including
      biotransformations. In this review, we have summarized the steroid transformation
      patterns of several microalgal strains and present a perspective of the future
      trends in microalgal biotechnology, including the possibility of adapting
      relatively new techniques, such as organic media catalysis and cell
      immobilization, to this specific field. 

PMID- 27041038
TI  - SHIFT FROM CHLOROPHYTES TO CYANOBACTERIA IN BENTHIC MACROALGAE ALONG A GRADIENT
      OF NITRATE DEPLETION(1).
AB  - A survey of the spatial distribution of benthic macroalgae in a fluvial lake of
      the St. Lawrence River (Lake Saint-Pierre, Quebec, Canada) revealed a shift in
      composition from chlorophytes to cyanobacteria along the flow path of nutrient
      rich waters originating from tributaries draining farmlands. The link between
      this shift and changes in water quality characteristics was investigated by
      sampling at 10 sites along a 15 km transect. Conductivity, current, light
      extinction, total phosphorus (TP; >25 MUg P . L(-1) ), and ammonium (8-21 MUg N .
      L(-1) ) remained fairly constant along the transect in contrast to nitrate
      concentrations, which fell sharply. Filamentous and colonial chlorophytes
      [Cladophora sp. and Hydrodictyon reticulatum (L.) Bory] dominated in the first 5
      km where nitrate concentrations were >240 MUg N . L(-1) . A mixed assemblage of
      chlorophytes and cyanobacteria characterized a 1 km transition zone where nitrate
      decreased to 40-80 MUg N . L(-1) . In the last section of the transect, nitrate
      concentrations dropped below 10 MUg N . L(-1) , and cyanobacteria (benthic
      filamentous mats of Lyngbya wollei Farl. ex Gomont and epiphytic colonies of
      Gloeotrichia) dominated the benthic community. The predominance of nitrogen
      fixing, potentially toxic cyanobacteria likely resulted from excessive nutrient
      loads and may affect nutrient and trophic dynamics in the river. 

PMID- 27041039
TI  - SELF-THINNING AND SIZE INEQUALITY DYNAMICS IN A CLONAL SEAWEED (SARGASSUM
      LAPAZEANUM, PHAEOPHYCEAE)(1).
AB  - Fronds of clonal seaweeds with extensive holdfasts relative to frond size are
      known not to self-thin during growth, even in crowded stands. We tested whether
      frond self-thinning would occur for such a seaweed since these traits are more
      similar to those of unitary seaweeds, which do self-thin in crowded conditions.
      We used Sargassum lapazeanum Setch. et N. L. Gardner (Fucales, Phaeophyceae) from
      the Pacific coast of Mexico, for which we first confirmed its clonal nature by
      performing a regeneration experiment in culture tanks. During the growth season
      (winter to late spring), S. lapazeanum stand biomass increased, while frond
      density and size inequality (Gini coefficient for frond biomass) decreased. These
      results indicate that self-thinning occurred at the frond level. We propose a
      conceptual model for frond dynamics for clonal seaweeds in general. In stands of
      clonal species with small fronds and relatively extensive holdfasts (particularly
      when holdfasts are perennial), frond dynamics would be determined mostly by
      intraclonal regulation, which seems to prevent excessive crowding from occurring.
      Such species display a positive biomass-density relationship during the growth
      season. On the contrary, in stands of clonal species with large fronds relative
      to holdfast size, frond dynamics would be determined mostly by interactions among
      genets. For such species, self-thinning may be detected at the frond level in
      crowded stands, resulting in a negative biomass-density relationship during
      growth. 

PMID- 27041040
TI  - CHANGES IN NUTRIENT CONTENT OF PALMARIA PALMATA IN RESPONSE TO VARIABLE LIGHT AND
      UPWELLING IN NORTHERN SPAIN(1).
AB  - Light has been identified as one of the main factors affecting seaweed
      ecophysiology. We investigated the dependence of nutrient metabolism on sun and
      shade light conditions and whether episodes of upwelling of nutrient-rich
      subsuperficial water could reduce the summer nutrient limitation driving
      physiological changes in Palmaria palmata (L.) Kuntze. We measured the major
      nutrient pools, photosynthetic pigments, and light curves, under sun and shade
      conditions during a summer period when one upwelling was recorded. The redundancy
      analysis (RDA) produced two clear groups: sun- and shade-acclimated algae. Light
      was the major predictive factor. Sun-acclimated algae exhibited higher carbon (C)
      and lower nitrogen (N) and phosphorus (P) content in association with the storage
      of floridoside (main C reserve) to benefit from higher irradiance (under nutrient
      limitation). Among N pools, N reserves (phycoerythrin, nitrate) were a lower
      proportion of the total N in sun-acclimated algae, suggesting their degradation
      to fulfill the N demands of the cell. The orthophosphate content was also lower
      in sun-acclimated algae, indicating its utilization as a nutrient reserve. In
      contrast, N within cell walls and membranes and chl a contributed to a similar
      proportion of the total N in sun- and shade-acclimated algae, suggesting a
      response to sustain cell integrity. Transient high nutrient concentration due to
      the upwelling was unrelated to the nutrient content of the thallus. The storage
      of C as floridoside from high light exposure was shown to be the driving force
      for the metabolic adjustment of P. palmata at the end of summer before the onset
      of dormancy. 

PMID- 27041041
TI  - DIVERSITY AND HOST SPECIFICITY OF AZOLLA CYANOBIONTS(1).
AB  - A unique, hereditary symbiosis exists between the water fern Azolla and
      cyanobacteria that reside within a cavity in the dorsal leaf-lobe of the plant.
      This association has been studied extensively, and questions have frequently been
      raised regarding the number and diversity of cyanobionts (cyanobacterial
      symbionts) among the different Azolla strains and species. In this work,
      denaturating gradient gel electrophoresis (DGGE) and a clone library based on the
      16S rRNA gene were used to study the genetic diversity and host specificity of
      the cyanobionts in 35 Azolla strains covering a wide taxonomic and geographic
      range. DNA was extracted directly from the cyanobacterial packets, isolated after
      enzymatic digestion of the Azolla leaves. Our results indicated the existence of
      different cyanobiont strains among Azolla species, and diversity within a single
      Azolla species, independent of the geographic origin of the host. Furthermore,
      the cyanobiont exhibited host-species specificity and showed most divergence
      between the two sections of genus Azolla, Azolla and Rhizosperma. These findings
      are in agreement with the recent redefinition of the taxon Azolla cristata within
      the section Azolla. With regard to the taxonomic status of the cyanobiont, the
      genus Anabaena of the Nostocaceae family was identified as the closest relative
      by this work. 

PMID- 27041042
TI  - ISOLATION OF A NON-PHAGE-LIKE LYTIC VIRUS INFECTING AUREOCOCCUS
      ANOPHAGEFFERENS(1).
AB  - We have been working to characterize viruses that infect the HAB-forming
      pelagophyte Aureococcus anophagefferens Hargraves et Sieburth. Field samples were
      collected during brown-tide events in 2002 and tested for the presence of lytic
      agents. Here, we describe a recently isolated, lytic virus-like particle (VLP)
      that is morphologically similar to particles observed in thin sections of
      infected A. anophagefferens cells from natural samples. TEM and SEM have revealed
      VLPs consistent with the morphological characteristics of previously described
      Phycodnaviridae. Large icosahedral particles (~140 nm) of similar shape and
      morphology dominate cell lysates and are accompanied by smaller phage-like
      particles and heterotrophic prokaryotes that appear to be incurable from our
      cultures. To determine which of these particles interacts with the Aureococcus
      cells, we preserved cultures during the early stage of infection so that SEM
      could be used to visualize those particles that attach to the surface of naive
      cultures. SEM revealed that 63% of the large icosahedral-shaped particles
      attached to A. anophagefferens cells after only 30 min of exposure, while no
      significant frequency of attachment to the alga was observed for the phage-like
      particles. The results of these observations are in contrast to previous studies,
      where phage-like particles were reported to infect cells. When considered in
      conjunction with field observations, the results suggest that this newly isolated
      virus represents the dominant virus-morphotype associated with bloom collapse and
      termination. 

PMID- 27041043
TI  - CILIATE-SYMBIONT SPECIFICITY OF FRESHWATER ENDOSYMBIOTIC CHLORELLA
      (TREBOUXIOPHYCEAE, CHLOROPHYTA)(1).
AB  - The nature of Chlorella symbioses in invertebrates and protists has attracted
      much interest, but the uncertain taxonomy of the algal partner has constrained a
      deeper ecological understanding of this symbiosis. We sequenced parts of the
      nuclear 18S rDNA, the internal transcribed spacer (ITS)-1 region, and the
      chloroplast 16S rDNA of several Chlorella isolated from pelagic ciliate species
      of different lakes, Paramecium bursaria symbionts, and free-living Chlorella to
      elucidate phylogenetic relationships of Chlorella-like algae and to assess their
      host specificity. Sequence analyses resulted in well-resolved phylogenetic trees
      providing strong statistical support for a homogenous 'zoochlorellae' group of
      different ciliate species from one lake, but clearly different Chlorella in one
      of those ciliate species occurring in another lake. The two Chlorella strains
      isolated from the same ciliate species, but from lakes having a 10-fold
      difference in underwater UV transparency, also presented a distinct physiological
      trait, such as the ability to synthesize UV-absorbing substances known as
      mycosporine-like amino acids (MAAs). Algal symbionts of all P. bursaria strains
      of different origin resolved in one clade apart from the other ciliate symbionts
      but split into two distinct lineages, suggesting the existence of a biogeographic
      pattern. Overall, our results suggest a high degree of species specificity but
      also hint at the importance of physiological adaptation in symbiotic Chlorella. 

PMID- 27041044
TI  - ANTIFEEDING DEFENSE IN BALTIC MACROALGAE: INDUCTION BY DIRECT GRAZING VERSUS
      WATERBORNE CUES(1).
AB  - The prevalence of antigrazing defense induction and the cues triggering induction
      in marine macroalgae are generally not well understood. We examined the capacity
      of defense and the mechanisms of regulation in five common perennial macroalgal
      species from the Baltic Sea, Furcellaria lumbricalis (Huds.) J. V. Lamour.,
      Delesseria sanguinea (Huds.) J. V. Lamour., Phyllophora pseudoceranoides (S. G.
      Gmel.) Newroth et A. R. A. Taylor, Fucus serratus L., and Fucus evanescens C.
      Agardh. Specifically, we investigated whether direct feeding and/or waterborne
      cues from feeding on neighboring conspecifics decreased the palatability of the
      tested algae. Direct feeding by the local isopod Idotea baltica triggered the
      induction of chemical defense in Fur. lumbricalis, D. sanguinea, P.
      pseudoceranoides, F. serratus, and F. evanescens. Conversely, we did not find any
      evidence for waterborne cues associated with feeding to trigger defense induction
      in neighboring conspecifics. 

PMID- 27041045
TI  - BICARBONATE STIMULATION OF CALCIFICATION AND PHOTOSYNTHESIS IN TWO HERMATYPIC
      CORALS(1).
AB  - A wide range of bicarbonate concentrations was used to monitor the kinetics of
      bicarbonate (HCO3 (-) ) use in both photosynthesis and calcification in two reef
      building corals, Porites porites and Acropora sp. Experiments carried out close
      to the P. porites collection site in Barbados showed that additions of NaHCO3 to
      synthetic seawater proportionally increased the calcification rate of this coral
      until the concentration exceeded three times that of seawater (6 mM).
      Photosynthetic rates were also stimulated by HCO3 (-) addition, but these became
      saturated at a lower concentration (4 mM). Similar experiments on aquarium
      acclimated colonies of Indo-Pacific Acropora sp. showed that calcification and
      photosynthesis in this coral were enhanced to an even greater extent than P.
      porites, with calcification continuing to increase above 8 mM HCO3 (-) , and
      photosynthesis saturating at 6 mM. Calcification rates of Acropora sp. were also
      monitored in the dark, and, although these were lower than in the light for a
      given HCO3 (-) concentration, they still increased dramatically with HCO3 (-)
      addition, showing that calcification in this coral is light stimulated but not
      light dependent. 

PMID- 27041046
TI  - ANALYSIS OF EXPRESSED SEQUENCE TAGS FROM THE MARINE MICROALGA NANNOCHLOROPSIS
      OCULATA (EUSTIGMATOPHYCEAE)(1).
AB  - Nannochloropsis oculata (Droop) D. J. Hibberd (Eustigmatophyceae), a marine
      eukaryotic unicellular alga, is widely used in mariculture as live feed. It is
      considered to be of high nutritional value owing to its high content of proteins;
      polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA,
      C20:5n3); and diverse pigments. Previous studies of this microalga focused on its
      taxonomy, culture, and biochemistry, but little is known at the molecular level.
      Establishing a molecular base is vital to understand the biological processes of
      this alga. Therefore, we constructed a cDNA library using algal cells grown at
      exponential growth phase and carried out expressed sequence tag (EST) analysis. A
      total of 1,960 nonredundant sequences (NRSs) were generated for N. oculata clone
      CS-179. Only 32.5% of NRSs showed significant similarity (E < 1e-04) to proteins
      registered in the GenBank nonredundant protein database. The KOG (clusters of
      euKaryotic Orthologous Groups) profile database returned significant hits for 490
      NRSs. Analysis revealed that a large proportion of NRSs could be unique to this
      microalga. 

PMID- 27041047
TI  - MOLECULAR CHARACTERIZATION OF THE LECTIN, BRYOHEALIN, INVOLVED IN PROTOPLAST
      REGENERATION OF THE MARINE ALGA BRYOPSIS PLUMOSA (CHLOROPHYTA)(1).
AB  - When a coenocytic cell of the green alga Bryopsis plumosa (Hudson) C. Agardh was
      cut open and the cell contents expelled, the cell organelles agglutinated rapidly
      in seawater to form protoplasts. This process was mediated by a lectin,
      Bryohealin. The full sequence of the cDNA encoding Bryohealin was obtained, which
      consisted of 1,101 base pairs (bp), with 24 bp of 5' untranslated region (UTR)
      and 201 bp of 3' UTR. It had an open reading frame (ORF) of 771 bp encoding 257
      amino acid residues. A signal peptide consisted of 22 amino acids presented
      before the start codon of Bryohealin, indicating that this lectin was a vacuolar
      (storage) protein. The C-terminal sequence of Bryohealin was composed of
      antibiotic domains, suggesting that this lectin could perform two functions: (i)
      aggregation of cell organelles in seawater and (ii) protection from bacterial
      contamination for successful protoplast regeneration. The BLAST search result
      showed that Bryohealin had little sequence homology with any known plant lectins,
      but rather resembled animal lectins with fucolectin domains. The expression of
      recombinant Bryohealin (rBryohealin) was obtained in the Escherichia coli system.

PMID- 27041048
TI  - IDENTIFICATION OF GENES PREFERENTIALLY EXPRESSED DURING ASEXUAL SPORULATION IN
      PORPHYRA YEZOENSIS GAMETOPHYTES (BANGIALES, RHODOPHYTA)(1).
AB  - Asexual reproduction via archeospores in Porphyra yezoensis Ueda gametophytes is
      a very valuable character to nori farming; however, there is little information
      available on the molecular basis of the developmental process. To identify genes
      involved in the Porphyra asexual sporulation, we compared the gene expression
      profiles derived from four developmental stages of the life cycle (three from
      gametophytes; one from sporophytes) using cDNA macroarray, which includes 4,896
      nonredundant expressed sequence tag (EST) groups. Candidate genes were screened
      by two different macroarray data analyses combined with reverse transcription-PCR
      (RT-PCR) analysis or Northern analysis. RT-PCR analysis revealed that nine genes
      (one: similarity to 5'-3' exoribonuclease; the other eight: no sequence
      similarity to known proteins) were expressed with a gametophyte (G)-specific
      manner, and two genes (named ASPO2608, ASPO1527) were expressed only in
      gametophytes that formed archeospores. The deduced amino acid sequences for the
      latter two genes are predicted to contain signal peptides for secretion at their
      N-termini. Northern analysis revealed that expression levels of Calvin cycle
      genes in the gametophytic stage that formed archeospores (G-A stage) were higher
      than those of the gametophyte blade with no archeospores (G-NA stage). In the
      macroarray analysis based on the rank data of G-preferentially expressed genes,
      which were detected in the previous P. yezoensis EST analysis, one gene encoding
      the cyclase associated protein (CAP) exhibited a change upwardly in the G-A stage
      >1,000 ranks to the G-NA stage. We propose that ASPO2608 and CAP may function in
      a signaling pathway of asexual sporulation. 

PMID- 27041049
TI  - CORRELATED EVOLUTION OF GENOME SIZE AND CELL VOLUME IN DIATOMS
      (BACILLARIOPHYCEAE)(1).
AB  - A correlation between genome size and cell volume has been observed across
      diverse assemblages of eukaryotes. We examined this relationship in diatoms
      (Bacillariophyceae), a phylum in which cell volume is of critical ecological and
      biogeochemical importance. In addition to testing whether there is a predictive
      relationship across extant species, we tested whether evolutionary divergences in
      genome size were correlated with evolutionary divergences in cell size (using
      independent contrasts). We estimated total DNA content for 16 diatom species
      using a flow cytometer and estimated cell volumes using critical dimensions with
      scaling equations. Our independent contrast analyses indicated a significant
      correlated evolution between genome size and cell volume. We then explored the
      evolutionary and ecological implications of this evolutionary relationship.
      Diatom cell volume is an important component of the global carbon cycle;
      therefore, understanding the mechanisms that drive diatom genome evolution has
      both evolutionary and ecological importance. 

PMID- 27041050
TI  - NOVEL PELLICLE SURFACE PATTERNS ON EUGLENA OBTUSA (EUGLENOPHYTA) FROM THE MARINE
      BENTHIC ENVIRONMENT: IMPLICATIONS FOR PELLICLE DEVELOPMENT AND EVOLUTION(1).
AB  - Euglena obtusa F. Schmitz possesses novel pellicle surface patterns, including
      the greatest number of strips (120) and the most posterior subwhorls of strip
      reduction in any euglenid described so far. Although the subwhorls form a
      mathematically linear pattern of strip reduction, the pattern observed here
      differs from the linear pattern described for Euglena mutabilis F. Schmitz in
      that it contains seven linear subwhorls, rather than three, and is
      developmentally equivalent to three whorls of exponential reduction, rather than
      two. These properties imply that the seven-subwhorled linear pattern observed in
      E. obtusa is evolutionarily derived from an ancestral bilinear pattern, rather
      than from a linear pattern, of strip reduction. Furthermore, analysis of the
      relative lateral positions of the strips forming the subwhorls in E. obtusa
      indicates that (1) the identity (relative length, lateral position, and maturity)
      of each strip in any mother cell specifies that strip's identity in one of the
      daughter cells following pellicle duplication and cell division, (2) the relative
      length of any given pellicle strip regulates the length of the nascent strip it
      will produce during pellicle duplication, and (3) pellicle pores develop within
      the heels of the most mature pellicle strips. These observations suggest that
      continued research on pellicle development could eventually establish an ideal
      system for understanding mechanisms associated with the morphogenesis and
      evolution of related eukaryotic cells. 

PMID- 27041051
TI  - MORPHOLOGICAL AND PHYLOGENETIC STUDIES ON UNICELLULAR DIAZOTROPHIC CYANOBACTERIA
      (CYANOPHYTES) ISOLATED FROM THE COASTAL WATERS AROUND SINGAPORE(1).
AB  - Six unicellular diazotrophic cyanobacteria were isolated from the coast around
      Singapore. The isolates grew under both light:dark (L:D) cycles and continuous
      illumination (CL) in media without combined nitrogen and exhibited an ability to
      fix nitrogen (as measured by acetylene reduction) under aerobic conditions. The
      cells of all isolates were surrounded by a thick fibrous outer wall layer, and
      they divided by transverse binary fission. The arrangement of photosynthetic
      thylakoids was of the dispersed type. Three isolates were identified as form
      genus Gloeothece as cells were divided in a single plane, and the other three
      isolates were identified as form-genus Gloeocapsa as cells were divided in
      multiple planes. Phylogenetic analyses based on the DNA sequences of the genes
      encoding 16S rRNA and dinitrogenase reductase (nifH) revealed the following: (i)
      Our six isolates formed a monophyletic cluster. (ii) The monophyletic cluster was
      subdivided into two phylogenetic groups, which taxonomically corresponded with
      the form-genera Gloeothece and Gloeocapsa. However, (iii) a diazotrophic strain
      of form-genus Gloeothece, Gloeothece membranacea (Rabenh.) Bornet PCC6501, was
      not closely related to our isolates, and (iv) some, but not all, diazotrophic
      unicellular strains of form-genus Cyanothece were observed to be in a close
      relationship with our isolates. 

PMID- 27041052
TI  - MORPHOLOGICAL VARIABILITY AND LIFE CYCLE TRAITS OF THE TYPE SPECIES OF THE DIATOM
      GENUS CHAETOCEROS, C. DICHAETA(1).
AB  - Chaetoceros dichaeta Ehrenb. is the type species of the genus Chaetoceros and is
      one of the dominant planktonic diatom species of the Southern Ocean. A number of
      varieties and forms have been described for C. dichaeta, which prompted us to
      investigate the morphological variability in clonal cultures to achieve a better
      circumscription of the morphological features of this species. We studied eight
      clonal cultures obtained from the type locality by sequencing the D1-D3
      hypervariable domains of the LSU to assess their genetic identity, following cell
      size reduction and sexual reproduction, and examining the morphological features
      of cells at different stages of the size reduction process using both LM and EM.
      Observation of sexual reproduction within clonal strains demonstrated that C.
      dichaeta is homothallic. The size and morphology of the cells vary considerably
      during size reduction: cell volume is reduced by over an order of magnitude, and
      the gradual diminution of the apical axis is accompanied by the elongation of the
      pervalvar axis. All forms and varieties described for C. dichaeta can be ascribed
      to the species, with the exception of C. dichaeta f. tenuiformis L. Mangin. 

PMID- 27041053
TI  - A UNIQUE LIFE CYCLE AND PERENNATION IN A COLORLESS CHRYSOPHYTE SPUMELLA SP.(1).
AB  - Life cycle and perennation of a colorless chrysophyte, Spumella sp., isolated
      from an ephemeral ditch were investigated. From a single resting cyst
      (statospore), only one nonmotile cell germinated. Shortly after germination, the
      cell generated flagella, started to swim, and formed a gelatinous sphere. The
      cell itself retained the ability to swim within the sphere. Cells fed on bacteria
      inhabiting the sphere and grew by longitudinal binary cell division very rapidly.
      The gelatinous sphere gradually enlarged as the number of cells increased. When
      it reached maximum size (~500 MUm in diameter), the gelatinous substance of the
      sphere weakened, and the sphere gradually broke into several pieces, forming
      cleavages between them. Cells swam away through the cleavages. Five to ~40
      swimming cells soon gathered and formed a swarm. In the swarm, some cells
      cannibalized other sibling cells and enlarged, resulting in giant cells that were
      two to three times larger in diameter than ordinary cells. The giant cells soon
      started statospore formation. Statospore formation was independent of any changes
      of environmental factors, such as increase or decrease in temperature or changes
      in nutrient or light levels, which are known to induce resting-cyst formation in
      other groups of algae and protists. Statospore formation started when cells
      divided 15 to 16 times after germination. This is congruent with the idea that
      statospore formation in planktonic chrysophytes directly depends on cell density.
      An extraordinarily high growth rate and cannibalism involved in the initiation of
      statospore formation are interpreted as adaptations to achieve the perennation in
      ephemeral aquatic environments. 

PMID- 27041054
TI  - PHYLOGEOGRAPHY OF THE GENUS SPONGITES (CORALLINALES, RHODOPHYTA) FROM CHILE(1).
AB  - Both the records and the descriptions of the crustose species of coralline algae
      on the southeastern coast of South America are from the early 1900s. Unlike other
      algae species on the coast of Chile, the biogeography and distribution of
      crustose corallines have not been studied despite their abundance. Through recent
      studies, it has been determined that the genus Spongites is the most conspicuous
      genus along the rocky intertidal of the Chilean coasts. It is also common to the
      entire coast of the Southern Hemisphere; however, the relationship between
      species and the possible reasons for their distribution is unknown. We used
      nuclear and mitochondrial genetic markers and SEM observations of morphological
      characters to examine Spongites samples from the Southern Hemisphere and to
      establish the phylogeographic relationships of Chilean Spongites with specimens
      from other southern coasts. The combination of these analyses revealed the
      following: (i) a monophyletic clade that represents the Chilean Spongites and
      (ii) a paraphyletic clade for South African, New Zealand, and Argentine samples.
      Consequently, we postulate two nonexclusive hypotheses regarding the relationship
      of Spongites species in the Southern Hemisphere: (i) a complex history of
      extinction, speciation, and recolonization that might have erased original
      Gondwanan split patterns, and (ii) an Antarctic Peninsula origin for the Chilean
      Spongites species. 

PMID- 27041055
TI  - ASSESSING PHYLOGENETIC AFFINITIES AND SPECIES DELIMITATIONS IN KLEBSORMIDIALES
      (STREPTOPHYTA): NUCLEAR-ENCODED rDNA PHYLOGENIES AND ITS SECONDARY STRUCTURE
      MODELS IN KLEBSORMIDIUM, HORMIDIELLA, AND ENTRANSIA(1).
AB  - Nuclear-encoded SSU, group I intron, and internal transcribed spacer (ITS) rDNA
      sequences were obtained for 16 strains of green algae representing species of
      Klebsormidium, Hormidiella attenuata, and Entransia fimbriata (for taxonomic
      authorities, see Table S1 in the supplementary material). The SSU phylogeny
      resolved a well-supported clade Klebsormidiales in the Streptophyta that
      comprised authentic Klebsormidium isolates described recently in a monograph by
      G. M. Lokhorst and various strains from culture collections. The H. attenuata and
      En. fimbriata pair was the sister group of Klebsormidium. Certain isolates from
      culture collections previously identified as "Klebsormidium" emerged as
      Trebouxiophyceae. Strains assigned to Koliella, Gloeotila, and Stichococcus
      previously allied with Klebsormidium because of shared morphological and
      ultrastructural characteristics also belonged to Trebouxiophyceae. Group I
      introns inserted at Escherichia coli position 516 were found in K. nitens and SAG
      strain 384-1, and at position 1506 in H. attenuata and En. fimbriata. Introns
      were not observed in other Klebsormidiales. Unambiguous alignment of ITS regions
      of Klebsormidiales was only possible after thermodynamic folding had predicted
      eight conserved helical domains. The ITS phylogeny provided support for five of
      the morphospecies recognized by Lokhorst (K. flaccidum, K. elegans, K. bilatum,
      K. crenulatum, K. mucosum), but the sequences of K. dissectum, K. fluitans, and
      K. nitens formed an unresolved clade. The species with the earliest origin in the
      Klebsormidium phylogeny was K. flaccidum. The incongruence between Lokhorst's
      morphology-based cladograms and the ITS phylogenies demonstrated the need for a
      critical reappraisal of the taxonomy and the morphological and molecular species
      concept in Klebsormidium on the basis of a more extensive taxonomic and
      geographic sampling strategy. 

PMID- 27041056
TI  - TWO TYPES OF AUXILIARY CELL AMPULLAE IN GRATELOUPIA (HALYMENIACEAE, RHODOPHYTA),
      INCLUDING G. TAIWANENSIS SP. NOV. AND G. ORIENTALIS SP. NOV. FROM TAIWAN BASED ON
      rbcL GENE SEQUENCE ANALYSIS AND CYSTOCARP DEVELOPMENT(1).
AB  - Few species in the genus Grateloupia have been investigated in detail with
      respect to the development of the auxiliary cell ampullae before or after
      diploidization. In this study, we document the vegetative and reproductive
      structures of two new species of Grateloupia, G. taiwanensis S.-M. Lin et H.-Y.
      Liang sp. nov. and G. orientalis S.-M. Lin et H.-Y. Liang sp. nov., plus a third
      species, G. ramosissima Okamura, from Taiwan. Two distinct patterns are reported
      for the development of the auxiliary cell ampullae: (1) ampullae consisting of
      three orders of unbranched filaments that branch after diploidization of the
      auxiliary cell and form a pericarp together with the surrounding secondary
      medullary filaments (G. taiwanensis type), and (2) ampullae composed of only two
      orders of unbranched filaments in which only a few cells are incorporated into a
      basal fusion cell after diploization of the auxiliary cell and the pericarp
      consists almost entirely of secondary medullary filaments (G. orientalis type).
      G. orientalis is positioned in a large clade based on rbcL gene sequence analysis
      that includes the type species of Grateloupia C. Agardh 1822, G. filicina. G.
      taiwanensis clusters with a clade that includes the generitype of Phyllymenia J.
      Agardh 1848, Ph. belangeri from South Africa; that of Prionitis J. Agardh 1851,
      Pr. lanceolata from Pacific North America; and that of Pachymeniopsis Y. Yamada
      ex Kawab. 1954, Pa. lanceolata from Japan. A reexamination of the type species of
      the genera Grateloupia, Phyllymenia, Prionitis, and Pachymeniopsis is required to
      clarify the generic and interspecific relationships among the species presently
      placed in Grateloupia. 

PMID- 27041057
TI  - A MOLECULAR SYSTEMATIC APPROACH TO EXPLORE DIVERSITY WITHIN THE SELLAPHORA PUPULA
      SPECIES COMPLEX (BACILLARIOPHYTA)(1).
AB  - The common and cosmopolitan freshwater benthic diatom Sellaphora pupula (Kutz.)
      Mereschk. is a model system for studying the nature of species in microalgae; the
      biological significance of morphological variation in this species complex has
      been widely demonstrated. The aim of this study was to establish a two-gene
      phylogeny (18S rDNA and rbcL) for 23 Sellaphora taxa, including 19 S. pupula
      aggregate (agg.) demes or species, S. bacillum (Ehrenb.) D. G. Mann, and S.
      laevissima (Kutz.) D. G. Mann. A range of analyses on separate and combined data
      sets indicated that Sellaphora is a monophyletic group containing four major
      clades. Of the traditionally recognized species, S. bacillum and S. laevissima
      are natural groups, but S. pupula is paraphyletic or polyphyletic because S.
      bacillum groups with S. pupula"small lanceolate" and S. lanceolata. Thickened
      bars at the poles of valves within the core "pupula-bacillum" group may be a
      morphological synapomorphy; the fossil record suggests that this group is at
      least 12 million years old. Otherwise, there was no clear pattern in the
      distribution of different morphologies among the major clades; each clade was
      also heterogeneous with respect to mating system. More intensive and extensive
      sampling will doubtless uncover even greater diversity; the challenge lies in its
      interpretation. Our results demonstrate the limitations of paleoecological,
      ecological, and biogeographical research based on morphospecies. 

PMID- 27041058
TI  - PROROCENTRUM LEVIS, A NEW BENTHIC SPECIES (DINOPHYCEAE) FROM A MANGROVE ISLAND,
      TWIN CAYS, BELIZE(1).
AB  - As part of a long-term study of benthic dinoflagellates from the Belizean barrier
      reef system, we report a new species: Prorocentrum levis M. A. Faust, Kibler,
      Vandersea, P. A. Tester et Litaker sp. nov. P. levis cells are oval in valve view
      and range in size from 40 to 44 MUm long and 37 to 40 MUm wide. Each valve
      surface is smooth, with 221-238 valve pores and 99-130 marginal pores. These
      pores are uniformly small and range in diameter from 0.13 to 0.19 MUm. Asexual
      reproduction in P. levis is atypical, occurring within a hyaline envelope, and
      produces long branching chains of adherent cells. A phylogenetic analysis of SSU
      rDNA indicated that of the Prorocentrum species sequenced so far, P. levis was
      most closely related to P. concavum. P. levis produces okadaic acid and
      dinophysis toxin-2 (DTX2). Further, SEM observations and SSU rDNA sequence for P.
      belizeanum M. A. Faust, which was isolated at the same time, are also presented. 

PMID- 27041059
TI  - NOVEL UNARMORED DINOFLAGELLATES FROM THE TOXIGENIC FAMILY KARENIACEAE
      (GYMNODINIALES): FIVE NEW SPECIES OF KARLODINIUM AND ONE NEW TAKAYAMA FROM THE
      AUSTRALIAN SECTOR OF THE SOUTHERN OCEAN(1).
AB  - Six new species of unarmored dinoflagellates in the family Kareniaceae were
      isolated from the Australian sector of the Southern Ocean in March 2006: Takayama
      tuberculata de Salas sp. nov, Karlodinium antarcticum de Salas sp. nov., Karl.
      ballantinum de Salas sp. nov., Karl. conicum de Salas sp. nov., Karl. corrugatum
      de Salas sp. nov., and Karl. decipiens de Salas et Laza-Martinez sp. nov. These
      new taxa were characterized using light and electron microscopy and sequencing of
      the LSU rDNA and are well supported based either on their morphology or molecular
      phylogeny. Takayama tuberculata, isolated just north of the polar front (55
      degrees -57 degrees  S), is genetically close to T. tasmanica, but smaller, with
      a significantly reduced number of amphiesmal vesicles. Medium-sized Karl.
      antarcticum, also isolated from near the polar front, is characterized by its
      long ovoid cell outline and very long apical groove. The small Karl. ballantinum
      has a very short apical groove. The large Karl. conicum has a distinct conical
      epicone and spherical posterior nucleus. The small Karl. corrugatum, from just
      south of the polar front, has distinctive parallel striations on the epicone
      surface and a distinctively shaped and placed ventral pore. The large and
      widespread Karl. decipiens, distributed through Southern Ocean waters from the
      polar front to Tasmanian coastal waters, and coastal Spain, has a helicoidal
      chloroplast arrangement and a large central nucleus. This study represents the
      first description of species in the potentially ichthyotoxic family Kareniaceae
      recorded from the Southern Ocean. 

PMID- 27041060
TI  - Microbes matter: herbivore gut endosymbionts play a role in breakdown of host
      plant toxins.

PMID- 27041061
TI  - Thrombotic microangiopathy: Caplacizumab accelerates resolution of acute acquired
      TTP.

PMID- 27041062
TI  - Aquatic vegetation in response to increased eutrophication and degraded light
      climate in Eastern Lake Taihu: Implications for lake ecological restoration.
AB  - Terrestrial and aquatic ecosystem degradation is widely recognized as a major
      global environmental and development problem. Although great efforts have been
      made to prevent aquatic ecosystem degradation, the degree, extent and impacts of
      this phenomenon remain controversial and unclear, such as its driving mechanisms.
      Here, we present results from a 17-year field investigation (1998-2014) of water
      quality and a 12-year remote sensing mapping (2003-2014) of the aquatic
      vegetation presence frequency (VPF) in Eastern Lake Taihu, a macrophyte-dominated
      bay of Lake Taihu in China. In the past 17 years, nutrient concentrations and
      water level (WL) have significantly increased, but the Secchi disk depth (SDD)
      has significantly decreased. These changes were associated with increased lake
      eutrophication and a degraded underwater light climate that further inhibited the
      growth of aquatic vegetation. In Eastern Lake Taihu, increased nutrients,
      chlorophyll a and WL, and a decreased SDD were all significantly correlated with
      a decreased VPF. NH4(+)-N concentration and SDD/WL were the most important
      controlling factors for VPF. Therefore, increased anthropogenic nutrient inputs
      and a degraded underwater light climate surely result in a decreased VPF. These
      results elucidate the driving mechanism of aquatic vegetation degradation and
      will facilitate Lake Taihu ecological restoration.

PMID- 27041063
TI  - Conditional Deletion of Fgfr3 in Chondrocytes leads to Osteoarthritis-like
      Defects in Temporomandibular Joint of Adult Mice.
AB  - Osteoarthritis (OA) in the temporomandibular joint (TMJ) is a common degenerative
      disease in adult, which is characterized by progressive destruction of the
      articular cartilage. To investigate the role of FGFR3 in the homeostasis of TMJ
      cartilage during adult stage, we generated Fgfr3(f/f); Col2a1-CreER(T2) (Fgfr3
      cKO) mice, in which Fgfr3 was deleted in chondrocytes at 2 months of age. OA-like
      defects were observed in Fgfr3 cKO TMJ cartilage. Immunohistochemical staining
      and quantitative real-time PCR analyses revealed a significant increase in
      expressions of COL10, MMP13 and AMAMTS5. In addition, there was a sharp increase
      in chondrocyte apoptosis at the Fgfr3 cKO articular surface, which was
      accompanied by a down-regulation of lubricin expression. Importantly, the
      expressions of RUNX2 and Indian hedgehog (IHH) were up-regulated in Fgfr3 cKO
      TMJ. Primary Fgfr3 cKO chondrocytes were treated with IHH signaling inhibitor,
      which significantly reduced expressions of Runx2, Col10, Mmp13 and Adamts5.
      Furthermore, the IHH signaling inhibitor partially alleviated OA-like defects in
      the TMJ of Fgfr3 cKO mice, including restoration of lubricin expression and
      improvement of the integrity of the articular surface. In conclusion, our study
      proposes that FGFR3/IHH signaling pathway plays a critical role in maintaining
      the homeostasis of TMJ articular cartilage during adult stage. 

PMID- 27041064
TI  - Fluorescence turn-on for the highly selective detection of nitric oxide in vitro
      and in living cells.
AB  - Nitric oxide (NO) is the first ubiquitous signaling molecule in the human body.
      The selective and sensitive detection of NO in vitro and in vivo is of high
      importance but remains challenging. Previous fluorescent probes for NO detection
      either are of poor water solubility or lack selectivity over intracellular
      biomolecules. Herein, we rationally designed a water-soluble, biocompatible,
      small molecular probe o-phenylenediamine-Phe-Phe-OH (1) for the highly selective
      and sensitive detection of NO in vitro and in living cells. 1 can react with NO
      and turn on the fluorescence emission at 367 nm via an ICT mechanism. In vitro
      tests indicated that 1 showed high selectivity for NO detection without
      interference from common anions, ROS/RNS, and intracellular biomolecules DHA, AA,
      or MGO. In PBS buffer, 1 was applied for detecting NO within the range of 0-12
      MUM with a LOD of 6 nM. Moreover, 1 was successfully applied to sense
      intracellularly generated NO in living cells. We anticipate that 1 could be
      potentially employed for studying the toxicity and bioactivity of NO in the near
      future. 

PMID- 27041065
TI  - Effectiveness and safety profile of 40% trichloroacetic acid and cryotherapy for
      plantar warts.
AB  - Plantar warts are one of the most common infectious skin disease caused by the
      human papillomavirus. In this study, cryotherapy with liquid nitrogen delivered
      by the physician, up to four treatments 2 weeks apart. Forty percent
      trichloroacetic acid (TCA) was applied to warts weekly up to four treatments. At
      the end of 4 weeks, the clinical improvement of the TCA group (n = 30) was six
      patients (20%) with no change, one patient (3.3%) with a mild response, 13
      patients (43.3%) with a moderate response and 10 patients (33.3%) with a good
      response. In the cryotherapy group, clinical responses were 12 patients (40%)
      with no change, four patients (13.3%) with a mild response, 12 patients (40%)
      with a moderate response and two patients (6.7%) with a good response. There was
      a statistically significant difference in improvement between the two treatment
      groups (P = 0.027). According to our results, TCA 40% is more effective for
      clearance of plantar warts with significantly improved long-term safety profile. 

PMID- 27041066
TI  - Abdominal emergencies in pediatrics.
AB  - Abdominal symptoms are among the most common reasons for pediatric emergency
      department visits, and abdominal pain is the most frequently reported symptom.
      Thorough history taking and physical examination can often reach the correct
      diagnosis. Knowing the abdominal conditions that are most common in each age
      group can help radiologists narrow the differential diagnosis. When imaging tests
      are indicated, ultrasonography is usually the first-line technique, enabling the
      diagnosis or adding relevant information with the well-known advantages of this
      technique. Nowadays, plain-film X-ray studies are reserved for cases in which
      perforation, bowel obstruction, or foreign body ingestion is suspected. It is
      also important to remember that abdominal pain can also occur secondary to basal
      pneumonia. CT is reserved for specific indications and in individual cases, for
      example, in patients with high clinical suspicion of abdominal disease and
      inconclusive findings at ultrasonography. We review some of the most common
      conditions in pediatric emergencies, the different imaging tests indicated in
      each case, and the imaging signs in each condition. 

PMID- 27041067
TI  - Hypopituitarism.
AB  - Hypopituitarism refers to deficiency of one or more hormones produced by the
      anterior pituitary or released from the posterior pituitary. Hypopituitarism is
      associated with excess mortality, a key risk factor being cortisol deficiency due
      to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or
      insidious, and the most common cause in adulthood is a pituitary adenoma, or
      treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed
      based on baseline blood sampling for thyroid stimulating hormone, gonadotropin,
      and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic
      hormone deficiency dynamic stimulation tests are usually needed. Repeated
      pituitary function assessment at regular intervals is needed for diagnosis of the
      predictable but slowly evolving forms of hypopituitarism. Replacement treatment
      exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone,
      and desmopressin. If onset is acute, cortisol deficiency should be replaced
      first. Modifications in replacement treatment are needed during the transition
      from paediatric to adult endocrine care, and during pregnancy.

PMID- 27041068
TI  - Anomalous dynamics of intruders in a crowded environment of mobile obstacles.
AB  - Many natural and industrial processes rely on constrained transport, such as
      proteins moving through cells, particles confined in nanocomposite materials or
      gels, individuals in highly dense collectives and vehicular traffic conditions.
      These are examples of motion through crowded environments, in which the host
      matrix may retain some glass-like dynamics. Here we investigate constrained
      transport in a colloidal model system, in which dilute small spheres move in a
      slowly rearranging, glassy matrix of large spheres. Using confocal differential
      dynamic microscopy and simulations, here we discover a critical size asymmetry,
      at which anomalous collective transport of the small particles appears,
      manifested as a logarithmic decay of the density autocorrelation functions. We
      demonstrate that the matrix mobility is central for the observed anomalous
      behaviour. These results, crucially depending on size-induced dynamic asymmetry,
      are of relevance for a wide range of phenomena ranging from glassy systems to
      cell biology. 

PMID- 27041069
TI  - Chromatin remodeling by curcumin alters endogenous aryl hydrocarbon receptor
      signaling.
AB  - The aim of this study was to gain more information about the mechanisms that
      regulate expression of the aryl hydrocarbon receptor (AHR) target gene CYP1A1.
      Human hepatoma cells (HepG2 and Huh7) and human immortalized keratinocytes
      (HaCaT) were treated with different concentrations of the dietary polyphenolic
      compound curcumin (CUR) alone or in combination with the natural AHR agonist 6
      formylindolo[3,2-b]carbazole (FICZ). In an earlier study, we described that CUR
      can activate the AHR indirectly by inhibiting metabolic clearance of FICZ. Here,
      we measured cell viability, activation of AHR signaling, oxidative stress and
      histone modifying activities in response to CUR at concentrations ranging from
      0.1 to 50 MUM. We observed apparent non-linear responses on cell viability and
      activation of AHR signaling. The CYP1A1 expression and the CYP1A1 enzyme activity
      in the presence of CUR reflected the histone acetylation efficiency observed in
      nuclear extracts. At the lowest concentration, CUR significantly decreased
      histone deacetylase activity and increased the FICZ-induced CYP1A1 activity. In
      contrast, at the highest concentration, CUR increased the formation of reactive
      oxygen species, significantly inhibited histone acetylation, and temporally
      decreased FICZ-induced CYP1A1 activity. The results suggest that CUR can both
      increase and decrease the accessibility of DNA and thereby influence
      transcriptional responses to the ligand-activated AHR. This suggestion was
      supported by the fact that chromatin remodeling treatments with trichostatin A,
      p300, or 5-aza-dC increased CYP1A1 transcription. We conclude that the AHR
      dependent transcriptional efficiency is modified by factors that influence the
      cellular redox status and the chromatin structure. 

PMID- 27041070
TI  - Lon protease and eiF2alpha are involved in acute, but not prolonged,
      antiretroviral induced stress response in HepG2 cells.
AB  - Lon protease, an ATP dependent mitochondrial protease, is important in
      mitochondrial protein maintenance. Disruption of protein homeostasis and
      mitochondrial dysfunction is associated with lipodystrophy, metabolic syndrome
      and accelerated aging, and are commonly observed in patients on long term
      antiretroviral therapy. Sirtuin 3 (SIRT3) is a post-translational regulator of
      Lon and regulates antioxidant response. We previously showed the nucleoside
      analogues (NRTIs), Zidovudine (AZT; 7.1 MUM), Stavudine (d4T; 4 MUM), and
      Tenofovir (TFV; 1.2 MUM) induced oxidative stress and mitochondrial dysfunction
      in human hepatoma (HepG2) cells at 24 h (h) and 120 h. We conducted a
      mitochondrial proteomic assessment of homeostasis in the same model, using the
      same NRTIs. Protein expression of Lon, SIRT3, heat shock protein (HSP) 60,
      phospho-eukaryotic translation initiation factor 2alpha (p-eIF2alpha; Ser51) and
      phospho-c-jun N-terminal kinase (p-JNK; Thr183/Tyr185) were quantified by western
      blots. The data showed all stress responses were significantly increased in HepG2
      cells by all antiretroviral drugs at 24 h (p < 0.0001); however, at 120 h, a
      significant depletion in the ATP-dependent proteins Lon (p = 0.00013) and HSP60
      (p < 0.0001) was observed. Proteins initiated by endoplasmic reticulum stress: p
      eIF2alpha (p = 0.001) and p-JNK (p = 0.0029), were significantly reduced
      following prolonged treatment. SIRT3 was maintained at elevated levels in the
      treated cells following prolonged exposure (p < 0.001). We conclude that the ATP
      dependent proteins are more relevant to acute toxicity, while SIRT3 confers
      protection over prolonged periods of toxicity. 

PMID- 27041071
TI  - TiO2 nanoparticles cause cell damage independent of apoptosis and autophagy by
      impairing the ROS-scavenging system in Pichia pastoris.
AB  - The wide applications of titanium dioxide nanoparticles (TiO2 NPs) increase the
      possibility of their exposure to ecosystems, and therefore an improved
      understanding of their effects to organisms is required. However, their potential
      toxicity on eukaryotes, especially fungi, needs further detailed investigation.
      Here, we investigated the effects of anatase TiO2 NPs on the reactive oxygen
      species (ROS)-scavenging system in the model fungal organism, Pichia pastoris.
      Results showed that the NPs entered cells and had toxicity to this fungus, and
      their toxicity was attributed to cell wall damage, cell membrane damage, and ROS
      accumulation, but not apoptosis or autophagy. Interestingly, the synthesized TiO2
      NPs impaired but not activated the ROS-scavenging system, which contributes to
      the cytotoxicity. Moreover, this impairment was associated with down-regulation
      of antioxidant-related genes, especially those genes involved in GSH regulation.
      Hence, GSH may play a key role in the interaction between TiO2 NPs and yeast
      cells. 

PMID- 27041072
TI  - Hydrogen sulfide modulates sub-cellular susceptibility to oxidative stress
      induced by myocardial ischemic reperfusion injury.
AB  - In this study, we compared the impact of H2S pre (HIPC) and post-conditioning
      (HPOC) on oxidative stress, the prime reason for myocardial ischemia reperfusion
      injury (I/R), in different compartments of the myocardium, such as the
      mitochondria beside its subpopulations (interfibrillar (IFM) and subsarcolemmal
      (SSM) mitochondria) and microsomal fractions in I/R injured rat heart. The
      results demonstrated that compared to I/R rat heart, HIPC and HPOC treated hearts
      shows reduced myocardial injury, enhanced antioxidant enzyme activities and
      reduced the level of TBARS in different cellular compartments. The extent of
      recovery (measured by TBARS and GSH levels) in subcellular fractions, were in the
      following descending order: microsome > SSM > IFM in both HIPC and HPOC. In
      summary, oxidative stress mediated mitochondrial dysfunction, one of the primary
      causes for I/R injury, was partly recovered by HIPC and HPOC treatment, with
      significant improvement in SSM fraction compared to the IFM. 

PMID- 27041073
TI  - Metabolomic application in toxicity evaluation and toxicological biomarker
      identification of natural product.
AB  - Natural product plays a vital role in disease prevention and treatment since the
      appearance of civilization, but the toxicity severely hinders its wide use. In
      order to avoid toxic effect as far as possible and use natural product safely,
      more comprehensive understandings of toxicity are urgently required. Since the
      metabolome represents the physiological or pathological status of organisms,
      metabolomics-based toxicology is of significance to observe potential injury
      before toxins have caused physiological or pathological damages. Metabolomics
      based toxicology can evaluate toxicity and identify toxicological biomarker of
      natural product, which is helpful to guide clinical medication and reduce adverse
      drug reactions. In the past decades, dozens of metabolomic researches have been
      implemented on toxicity evaluation, toxicological biomarker identification and
      potential mechanism exploration of nephrotoxicity, hepatotoxicity, cardiotoxicity
      and central nervous system toxicity induced by pure compounds, extracts and
      compound prescriptions. In this paper, metabolomic technology, sample
      preparation, data process and analysis, and metabolomics-based toxicological
      research of natural product are reviewed, and finally, the potential problems and
      further perspectives in toxicological metabolomic investigations of natural
      product are discussed. 

PMID- 27041074
TI  - A novel biologically active acid stable liposomal formulation of docosahexaenoic
      acid in human breast cancer cell lines.
AB  - PURPOSE: The risk of breast cancer can be influenced by certain dietary
      components, such as the amount and type of dietary fatty acids ingested.
      Docosahexaenoic acid (DHA), a component of fish oil, is known to suppress rat
      mammary carcinogenesis, reduce cell growth and induce apoptosis in human breast
      cancer cell lines. The purpose of this study was to develop a novel nanoliposomal
      formulation that would encapsulate a concentrated amount of DHA and utilize
      lipids that could protect DHA from pH fluctuations and oxidation. METHODS: We
      developed an acid stable liposome formulation of DHA by utilizing ether and
      phytanyl lipids similar in structure to those found in Archaea, known to endure
      high acidity and temperature; we compared its biological activities with free DHA
      in human breast cancer cells. RESULTS: The mean size of the liposomal DHA was 137
      +/- 12 nm with a slightly negative charge; the encapsulation efficiency of DHA in
      the liposomes as determined by LC-MS/MS ranged from 60 to 80%; our formulation is
      resistant to oxidation and stable over a range of pH (1.0-7.4) at 37  degrees C
      for a duration of two hours. In MCF-7 cells, liposomal DHA (IC50 38.8 MUM)
      significantly reduced cell viability more effectively than free DHA (IC50 72.5
      MUM, p = 0.0017). In MDA-MB-231 cells, liposomal DHA was also marginally more
      effective. Liposomal DHA was more effective than free DHA in inducing apoptosis
      in both cell lines. It altered proteins involved in cell growth, cell cycle, and
      apoptosis more effectively than free DHA in both cell lines; it up-regulated p21
      and cleaved PARP, while P-AKT and P-S6 were down-regulated. CONCLUSIONS: We
      developed a novel biologically active acid stable liposomal DHA as a potentially
      useful formulation for breast cancer prevention.

PMID- 27041075
TI  - Therapeutic activity of modified U1 core spliceosomal particles.
AB  - Modified U1 snRNAs bound to intronic sequences downstream of the 5' splice site
      correct exon skipping caused by different types of mutations. Here we evaluate
      the therapeutic activity and structural requirements of these exon-specific U1
      snRNA (ExSpeU1) particles. In a severe spinal muscular atrophy, mouse model,
      ExSpeU1, introduced by germline transgenesis, increases SMN2 exon 7 inclusion,
      SMN protein production and extends life span. In vitro, RNA mutant analysis and
      silencing experiments show that while U1A protein is dispensable, the 70K and
      stem loop IV elements mediate most of the splicing rescue activity through
      improvement of exon and intron definition. Our findings indicate that precise
      engineering of the U1 core spliceosomal RNA particle has therapeutic potential in
      pathologies associated with exon-skipping mutations. 

PMID- 27041076
TI  - Combined use of intraoperative indocyanine green and dynamic angiography in
      rotational vertebral artery occlusion.
AB  - Rotational vertebral artery occlusion, also known as bow hunter's syndrome, is a
      well-documented surgically amenable cause of vertebrobasilar insufficiency.
      Traditionally, patients have been imaged using dynamic rotational angiography.
      The authors sought to determine whether intraoperative indocyanine green (ICG)
      angiography could reliably assess the adequacy of surgical decompression of the
      vertebral artery (VA). The authors report two patients who presented with
      multiple transient episodes of syncope provoked by turning their head to the
      right. Rotational dynamic angiography revealed a dominant VA that became occluded
      with head rotation to the right side. The patients underwent successful surgical
      decompression of the VA via an anterior cervical approach. Intraoperative ICG
      angiography demonstrated patency of the VA with head rotation. This was further
      confirmed by intraoperative dynamic catheter angiography. To our knowledge, we
      present the first two cases of the use of ICG combined with intraoperative
      dynamic rotational angiography to document the adequacy of surgical decompression
      of the VA in a patient with rotational vertebral artery occlusion. Intraoperative
      ICG angiography is a useful adjunct and may potentially supplant the need for
      intraoperative catheter angiography. 

PMID- 27041077
TI  - Ultrasound echomyography of facial muscles in diagnosis and follow-up of facial
      palsy in children.
AB  - BACKGROUND: Ultrasonography is a reliable, non-invasive and painless tool for
      quantitative assessment of the static and dynamic changes of the facial muscles
      in adult patients with facial palsy. Therefore it would also be worthwhile to
      establish the method for quantitative analysis of facial muscles in children with
      facial palsy to improve and expand the diagnostics for paediatric facial palsy.
      METHODS: Eight children, aged 1-18 years, with facial palsy of different
      aetiology were scanned and their ultrasound-images analysed. Bilateral scans of
      the frontal, orbicularis oculi, zygomaticus major, orbicularis oris, depressor
      anguli oris, depressor labii inferioris, and mentalis muscle were performed at
      rest and if possible during contraction. Muscle cross-section area, muscle
      thickness and echo intensity were measured. RESULTS: All muscles of our
      investigation protocol for adults could also be reliably identified in children.
      On the paralyzed side of the face a reduction of muscle size in rest and
      contraction and higher echo intensity could be convincingly detected. Based on
      these observations, we were able to make well-founded treatment decisions and
      avoid painful electrophysiological examinations. CONCLUSION: Ultrasonography of
      facial muscles is also feasible in children and facilitates diagnostics in
      children with facial palsy.

PMID- 27041078
TI  - Use of m-Health Technology for Preventive Interventions to Tackle Cardiometabolic
      Conditions and Other Non-Communicable Diseases in Latin America- Challenges and
      Opportunities.
AB  - In Latin America, cardiovascular disease (CVD) mortality rates will increase by
      an estimated 145% from 1990 to 2020. Several challenges related to social
      strains, inadequate public health infrastructure, and underfinanced healthcare
      systems make cardiometabolic conditions and non-communicable diseases (NCDs)
      difficult to prevent and control. On the other hand, the region has high mobile
      phone coverage, making mobile health (mHealth) particularly attractive to
      complement and improve strategies toward prevention and control of these
      conditions in low- and middle-income countries. In this article, we describe the
      experiences of three Centers of Excellence for prevention and control of NCDs
      sponsored by the National Heart, Lung, and Blood Institute with mHealth
      interventions to address cardiometabolic conditions and other NCDs in Argentina,
      Guatemala, and Peru. The nine studies described involved the design and
      implementation of complex interventions targeting providers, patients and the
      public. The rationale, design of the interventions, and evaluation of processes
      and outcomes of each of these studies are described, together with barriers and
      enabling factors associated with their implementation.

PMID- 27041079
TI  - Neferine prevents NF-kappaB translocation and protects muscle cells from
      oxidative stress and apoptosis induced by hypoxia.
AB  - Neferine (Nef), a bisbenzylisoquinoline alkaloid from lotus seed embryo has a
      wide range of pharmacological activities. Possible molecular mechanism for the
      cytoprotective action of Nef during hypoxic stress has not been explored till
      now. Hence, this is an attempt to elucidate the molecular mechanism involved in
      the Nef mediated cytoprotection on hypoxia-induced cell injury. Cytoprotective
      dose of Nef in muscle cells (Human rhabdomyosarcoma cells) exposed to hypoxia was
      determined by MTT assay. Nef at 500 nM offered better cytoprotection and was used
      for all the experiments. ROS, intracellular calcium accumulation and
      mitochondrial membrane (DeltapsiM) potential were measured using fluorescent
      probes. Further, we evaluated the effect Nef on hypoxia induced inflammatory and
      apoptotic responses by FACS and analyzing the expression patterns of NF-kappaB,
      COX-2, HIF-1alpha, caspase-3, caspase-9, Bcl2, and Bax. The results of this study
      revealed that pretreatment of the cells with Nef significantly decreased the
      DeltapsiM and ROS in the cells subjected to hypoxia. Further, Nef inhibited NF
      kappaB there by inhibiting the expression of its downstream regulator COX-2,
      while it induced the functional HIF-1alpha expression. The results also indicate
      that Nef significantly inhibited the ROS dependent mitochondrial mediated
      apoptosis induced during hypoxia. The cytoprotection elicited by Nef in a model
      of hypoxia induced cell death involves both anti-inflammatory and anti-apoptotic
      response. These results suggest that Nef may be used as prophylactic agent
      against the hypoxic challenge. (c) 2016 BioFactors, 42(4):407-417, 2016. 

PMID- 27041080
TI  - [Methodology for Identification of Inverse Drug Distribution, Spain].
AB  - OBJECTIVE: The phenomenon of reverse drug trafficking in the legal supply chain
      is an unlawful practice to serious risks to public health. The aims was to
      identify proactively pharmacies that carry out these illegal activities. METHODS:
      An analysis was performed through the crossing billing data to SAS of 52 million
      packs of medicines for the 496 pharmacies in the province over a period of 29
      months with the drug packaging data supplied by the distribution entities of the
      province with the implementation of specific indicator defined called 'percentage
      overbought' allows us to detect those pharmacies at high risk of being involved
      in this illicit trade. RESULTS: It was tested in two pharmacies one rural and
      other urban a detour of 5.130 medicine containers and an illicit profit obtained
      from ? 9,591.78 for the first and 9.982 packaging and ? 26,885.11 for the second;
      they had gone unnoticed in previous inspections. CONCLUSIONS: The methodology
      implemented to define a profile of infringing pharmacies high risk in these
      illicit practices, identify new ones that had not been sanctioned, weigh the
      drugs for illegal trade and to identify new drugs subject to diversion; also
      added as a challenge, it helps to adjust accurately and effectively calculate the
      illicit profit obtained.

PMID- 27041081
TI  - Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation.
AB  - Vitamin D is a secosteroid hormone that plays an important regulatory role in
      calcium homeostasis and bone metabolism. Immune cells can both produce and
      respond to 1,25(OH)2D3. CD4+ T cells from vitamin D receptor (VDR) KO mice
      produce higher levels of IFN-gamma and IL-17 than their wild type counterparts,
      and play a crucial role in the pathogenesis of autoimmune diseases (AID). We are
      particularly interested in studying the effect of vitamin D on pathogenic Th17
      cells in humans. We investigated the in vitro effect of 1,25(OH)2D3 and 25(OH)D3
      on the differentiation and cytokine production of primary CD4+ T cells from
      normal donors, and cultured in Th17 polarizing conditions. Both forms of vitamin
      D reduced the expression of pathogenic Th17 markers and their secretion of pro
      inflammatory cytokines (IL-17A, IFN-gamma). Furthermore, both vitamin D forms
      induced an expansion of CD25hi cells and upregulated their expression of CTLA-4
      and Foxp3 regulatory markers. 

PMID- 27041082
TI  - Emergency Department Management of Transient Ischemic Attack: A Survey of
      Emergency Physicians.
AB  - BACKGROUND: Patients are at high risk for stroke following a transient ischemic
      attack (TIA). The ideal setting for evaluating and treating patients with TIA has
      not been established, resulting in variability in emergency department (ED) TIA
      management. We conducted a survey to describe ED TIA management and factors that
      influence disposition determination for TIA patients. METHODS: We administered a
      mail survey to 480 randomly selected members of the Michigan College of Emergency
      Physicians. Survey questions addressed current ED TIA management, the
      acceptability of the ABCD(2) risk-stratification tool, and disposition
      recommendations for a series of hypothetical TIA patients. RESULTS: A total of
      188 (39%) responses were received. Head computed tomography (96.2%) and
      antiplatelet therapy (88.2%) were the most commonly reported ED interventions.
      Over 85% of respondents reported admitting most or all TIA patients. The ABCD(2)
      score had low acceptability among emergency medicine physicians and was rarely
      incorporated into practice (10.7%). Respondents identified a short-term risk of
      stroke of less than 2% (95% confidence interval: 1.6-2.4) as an acceptable
      threshold for discharge; however, most respondents recommended admission even for
      low-risk TIA patients. Those with access to an outpatient TIA clinic were less
      likely to admit low-risk TIA patients; those with access to an observation unit
      were more likely to admit. CONCLUSIONS: In this survey, ED physicians preferred
      hospital admission for most TIA patients, including those at low risk for stroke.
      The ABCD(2) risk-stratification tool had low acceptability. Further research is
      needed to refine risk-stratification tools and define the optimal setting for TIA
      evaluations.

PMID- 27041083
TI  - Thyrotoxic Periodic Paralysis: A Concise Review of the Literature.
AB  - BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare disease entity
      highlighted by hypokalemia, flaccid paralysis, and thyrotoxicosis. It usually
      presents as sudden profound muscle weakness manifested as almost complete
      immobility and can affect proximal and distal limb muscles, respiratory
      musculature as well as the cardiac conduction system. METHODS: A comprehensive
      review of Thyrotoxic periodic paralysis from 1885 to date was carried out by an
      extensive and thorough literature research including but not limited to Pubmed,
      Medline and EMBASE. OBJECTIVE: This review emphasizes the etiology, pathogenesis,
      management and prognosis of TPP and aims to highlight clinical awareness of early
      diagnosis and rapid initiation of treatment. CONCLUSION: It is extremely
      important to diagnose this condition as early as possible as it is potentially
      reversible and prompt treatment leads to rapid resolution with no residual
      weakness. Missing the diagnosis can result in possible fatal complications such
      as hypercapneic respiratory failure and ventricular fibrillation.

PMID- 27041084
TI  - The Effect of TNFalpha-Inhibitors on Cardiovascular Events in Patients with
      Rheumatoid Arthritis: An Updated Systematic Review of the Literature.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is strongly associated with cardiovascular
      morbidity and mortality. Previous studies have demonstrated that TNFalpha
      inhibitors may reduce cardiovascular events (CVE) in patients with RA. Thus, the
      purpose of this systematic review was to evaluate the ability of TNFalpha
      inhibitors to reduce the risk of CVE in patients with RA. This study will update
      the findings of two earlier systematic reviews that synthesized the data up until
      2010. . METHODS: A search of Medline, Embase, Medline In-Process and Other Non
      Indexed Citations, American College of Physicians Journal Club, Database of
      Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled
      Trials was conducted for observational studies reporting on CVE in RA patients
      since 2009. Conference proceedings for the Canadian Rheumatology Association,
      American College of Rheumatology, and European League against Rheumatism were
      also searched between 2009 and 2014. Abstracts were assessed for inclusion by two
      reviewers and studies identified by either reviewer were brought forward to full
      text review. Studies undergoing full-text review were further assessed based on
      predefined inclusion and exclusion criteria and the quality of selected papers
      was evaluated using the Newcastle-Ottawa Scale. . RESULTS: The search identified
      6089 abstracts and 14 articles were included in the final systematic review. Of
      the studies included, 8 reported on the effect of TNFalpha-inhibitors on overall
      CVE, 10 reported on coronary artery disease (CAD), 6 reported on cerebrovascular
      disease (CVD), and 5 reported other clinical cardiovascular outcomes. .
      CONCLUSION: TNFalpha-inhibitors appear to reduce the likelihood of overall CVE in
      individuals with RA. The reduction is not as pronounced in the individual outcome
      measures. These results are consistent with two previous systematic reviews
      suggesting that TNFalpha-inhibitors are likely useful in the prevention of
      cardiovascular complications of RA.

PMID- 27041085
TI  - Probing The Relation Between Vitamin D Deficiency and Progression of Medial
      Femoro-tibial Osteoarthitis of the Knee.
AB  - OBJECTIVE: To compare serum 25 OH vitamin D (25 (OH) D) levels between medial
      femoro-tibial knee osteoarthritis (OA) patients and controls, and to detect
      structural progression in patients with mild to moderate knee osteoarthritis in
      relation to baseline 25(OH) D levels in a oneyear longitudinal prospective cohort
      study. METHODS: Thirty eight patients with medial femoro-tibial knee OA according
      to the ACR criteria and no knee malalignement, and 20 age, sex and BMI-matched
      pain free controls were included in the vitamin D study. All included OA patients
      had radiographic Kellgren and Lawrence grades 2 or 3. Baseline serum levels of
      25(OH) D, and the "Benefiting from ultraviolet index "(BFUI) score were
      determined; serum parathormone, total alkaline phosphatase, calcium and
      phosphorus were measured. In the OA progression study, OA patients were divided
      into 2 groups according to 25 (OH) D level using a cutoff of 10 ng/ml to identify
      their status. MRIs were done at baseline and repeated after 12 months with
      scoring system according to Boston Leeds osteoarthritis knee score (BLOKS).
      During the study period, the patients were not supplemented with 25(OH)D.
      RESULTS: The mean values of Vitamin D were statistically lower in the OA patient
      group than in controls (8.64 +/- 6.42 vs. 14.84+/-0.87 pg/mL, P =0.0295). The
      BFUI score overall correlated with 25 (OH) D status. Eight patients did not
      complete the study so only thirty OA patients underwent the 2 MRIs. Of those, 21
      had 25(OH) D levels <10 ng/ml, while 9 had levels >10 ng/ml. A significant
      progression of the medial meniscal grading from baseline to 1 year was seen in
      the patients with 25(OH)D levels <10 ng/ml as compared to the others (Wilcoxon Z=
      -3.556 P<0.001). CONCLUSION: 25 (OH) D levels were significantly decreased in
      knee OA patients. Significant deterioration of the medial menisci was observed in
      OA patients with 25 (OH)D levels <10 ng/ml suggesting that Vit D deficiency may
      play a role in the progression of medial femoro-tibial OA.

PMID- 27041086
TI  - Pediatric Lupus Nephritis-Review of Literature.
AB  - Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder
      characterized by immune dysregulation and formation of autoantibodies. A high
      index of suspicion is necessary to diagnose SLE. Children have more systemic
      involvement than adults. Kidney involvement is seen in a significant proportion
      of children. With advancement of therapy the survival rate of patients with SLE
      has significantly improved. Even then lupus nephritis is still the most important
      predictor of morbidity and mortality. Treatment of lupus nephritis is mostly
      derived from studies in adults as data on children is still lacking. Prednisolone
      and cyclophosphamide was the mainstay of treatment till now. Recently drugs like
      mycophenolate mofetil, azathioprine, rituximab are also being used in treatment
      of lupus nephritis with promising results and without significant adverse
      effects. In this review we will be discussing lupus nephritis, its diagnosis,
      pathogenesis, clinical picture and treatment advancements.

PMID- 27041088
TI  - Turning certainties upside down: A homage to the work of Professor Robert L.
      Spitzer.

PMID- 27041087
TI  - Rapid height growth after liver transplantation in adulthood.
AB  - Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by
      glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia,
      hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The
      exact mechanism of short stature in this disease is unclear, the most feasible
      possibility is that it is caused by impairment of growth-hormone and insulin-like
      growth factor I axis. Here we report the case of a patient who showed typical
      symptoms of glycogen storage disease Ib since his infancy, his height being under
      1 percentile since then. Later-developed hypothyroidism and hypogonadism have
      also contributed to his short stature. Hypothyroidism was treated but sexual
      steroid substitution was not started because of an increased risk of hepatic
      adenomas. Because he developed hepatic adenoma at the age of 23, he had to
      undergo orthotopic liver transplantation. At the time of the transplantation his
      height was 128cm. The transplantation was followed by rapid height growth; our
      patient's height reached 160.3cm 62months after transplantation. We observed that
      while his IGF-I level increased, his GH level remained unchanged. During the post
      transplantation period we ensured adequate calcium and vitamin D supplementation,
      leaving hormonal substitution unchanged. According to our knowledge, this is the
      first report of a rapid height growth as big as 32cm, of an individual over the
      age of 20, not related to endocrine treatment but liver transplantation.

PMID- 27041089
TI  - Direct effects of airborne PM2.5 exposure on macrophage polarizations.
AB  - BACKGROUND: Exposure of atmospheric particulate matter with an aerodynamic
      diameter less than 2.5MUm (PM2.5) is epidemiologically associated with illnesses.
      Potential effects of air pollutants on innate immunity have raised concerns. As
      the first defense line, macrophages are able to induce inflammatory response.
      However, whether PM2.5 exposure affects macrophage polarizations remains unclear.
      METHODS: We used freshly isolated macrophages as a model system to demonstrate
      effects of PM2.5 on macrophage polarizations. The expressions of cytokines and
      key molecular markers were detected by real-time PCR, and flow cytometry. The
      specific inhibitors and gene deletion technologies were used to address the
      molecular mechanisms. RESULTS: PM2.5 increased the expression of pro-inflammatory
      cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin
      6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha).
      PM2.5 also enhanced the lipopolysaccharide (LPS)-induced M1 polarization even
      though there was no evidence in the change of cell viability. However, PM2.5
      significantly decreased the number of mitochondria in a dose dependent manner.
      Pre-treatment with NAC, a scavenger of reactive oxygen species (ROS), prevented
      the increase of ROS and rescued the PM2.5-impacted M1 but not M2 response.
      However, mTOR deletion partially rescued the effects of PM2.5 to reduce M2
      polarization. CONCLUSIONS: PM2.5 exposure significantly enhanced inflammatory M1
      polarization through ROS pathway, whereas PM2.5 exposure inhibited anti
      inflammatory M2 polarization through mTOR-dependent pathway. GENERAL
      SIGNIFICANCE: The present studies suggested that short-term exposure of PM2.5
      acts on the balance of inflammatory M1 and anti-inflammatory M2 macrophage
      polarizations, which may be involved in air pollution-induced immune disorders
      and diseases. This article is part of a Special Issue entitled Air Pollution,
      edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.

PMID- 27041090
TI  - A new fully integrated X-ray irradiator system for dosimetric research.
AB  - A fully housed X-ray irradiator was developed for use within lexsyg or Magnettech
      desktop equipment. The importance of hardening of the low energy photon radiation
      is discussed, its performance and feasibility is empirically shown and sustained
      by basic numerical simulations. Results of the latter for various materials are
      given for different X-ray source settings in order to provide estimates on the
      required setup for the irradiation of different geometries and materials. A Si
      photodiode provides real-time monitoring of the X-ray-irradiator designed for use
      in dosimetric dating and other dosimetric application where irradiation of small
      samples or dosemeters is required.

PMID- 27041091
TI  - Transformation of irregular shaped silver nanostructures into nanoparticles by
      under water pulsed laser melting.
AB  - The ability to easily manufacture nanostructures with a desirable attribute, such
      as well-defined size and shape, especially from any given initial shapes or sizes
      of the material, will be helpful towards accelerating the use of nanomaterials in
      various applications. In this work we report the transformation of discontinuous
      irregular nanostructures (DIN) of silver metal by rapid heating under a bulk
      fluid layer. Ag films were changed into DIN by dewetting in air and subsequently
      heated by nanosecond laser pulses under water. Our findings show that the DIN
      first ripens into elongated structures and then breaks up into nanoparticles.
      From the dependence of this behavior on laser fluence we found that under water
      irradiation reduced the rate of ripening and also decreased the characteristic
      break-up length scale of the elongated structures. This latter result was
      qualitatively interpreted as arising from a Rayleigh-Plateau instability modified
      to yield significantly smaller length scales than the classical process due to
      pressure gradients arising from the rapid evaporation of water during laser
      melting. These results demonstrate that it is possible to fabricate a dense
      collection of monomodally sized Ag nanoparticles with significantly enhanced
      plasmonic quality starting from the irregular shaped materials. This can be
      beneficial towards transforming discontinuous Ag films into nanostructures with
      useful plasmonic properties, that are relevant for biosensing applications. 

PMID- 27041092
TI  - Eating at the table, on the couch and in bed: An exploration of different locus
      of commensality in the discourses of Brazilian working mothers.
AB  - BACKGROUND: Commensality is a remarkable human act, and tends to be more present
      among families. Nevertheless, it is possible that eating at the table is being
      taking for granted when one refers to family meals. Thus, this paper aims to
      analyze working mothers' discourses about family meals eaten at the table, on the
      couch and in the bed/bedroom. METHODS: The participants were thirty mothers
      working in public universities of the Brazilian region called Baixada Santista. A
      qualitative study was conducted, using semi-structured interviews. In the
      transcripts the words "table", "couch", "bed", "bedroom" were located and the
      excerpts containing them were extracted and analyzed according to a classical and
      exploratory content analysis. RESULTS: The table is a significant component of
      meals that unite the family. While for some the meal at the table is an enjoyable
      moment, it is a stiff moment for others. Indeed, manners and the notion of
      hierarchy appeared only for the table. Regarding the couch, it seems that the
      family chose to eat there, because it is a more casual and relaxed setting.
      Eating in the bed was related to precarity, intimacy and casualness. In the three
      settings, watching television was a common practice, replacing or being added to
      talking. CONCLUSIONS: Commensality is such an important practice that appears in
      different settings and even in precarity contexts. The table emerged as the
      maximal cornerstone of commensality. However, when it was not present, new
      arrangements were made. Especially the couch seems to be a new commensal space,
      less formal and rigid, but able to allow some collective conviviality. Eating in
      the bed was a less common practice. Finally, the significant role that television
      assumed in meals is highlighted.

PMID- 27041093
TI  - ECTES Abstracts 2016.

PMID- 27041094
TI  - Improving glucocorticoid replacement in patients with adrenal insufficiency.

PMID- 27041095
TI  - Age-related fibromuscular dysplasia in the human left ventricle papillary muscles
      arteries.
AB  - We describe histologically cases of patients between 31 and 60 years of age who
      had fibromuscular dysplasia (FMD) in the tunica media (TM) of the left ventricle
      papillary muscles (PM) arteries. We also compared them with our previous findings
      in subjects younger than 30 years of age. We examined histologically samples
      taken from the tip of the anterior PM of the left ventricle in 200 healthy male
      hearts. In 33 cases (16.5 %), FMD was in the TM. We divided these cases into
      three subgroups (A, B, C) based on the degree of replacement of smooth muscle
      cells by fibrous tissue, and thus identified 17, 11 and 5 cases, respectively.
      Until the age of 41, the typical lesions were often localized within the TM.
      Beyond that age, the fibrous tissue increased in the TM wall and in the
      surrounding area of the vessels, causing dysfunction of the PM. Degenerative
      lesions, as well as inflammatory infiltration, were found after the age of 53.
      The findings of this study will be useful to cardiologists and cardiac surgeons,
      in pointing out that, after the age of 44 years old, some PM and their supporting
      valves may present a degree of dysfunction.

PMID- 27041096
TI  - Compound Mutations Cause Increased Cardiac Events in Children with Long QT
      Syndrome: Can the Sequence Homology-Based Tools be Applied for Prediction of
      Phenotypic Severity?
AB  - Long QT syndrome (LQTS) can cause syncope, ventricular fibrillation, and death.
      Recently, several disease-causing mutations in ion channel genes have been
      identified, and compound mutations have also been detected. It is unclear whether
      children who are carriers of compound mutations exhibit a more severe phenotype
      than those with single mutations. Although predicting phenotypic severity is
      clinically important, the availability of prediction tools for LQTS is unknown.
      To determine whether the severity of the LQTS phenotype can be predicted by the
      presence of compound mutations in children is needed. We detected 97 single
      mutations (Group S) and 13 compound mutations (Group C) between 1998 and 2012,
      age at diagnosis ranging 0-19 years old (median age is 9.0) and 18.0 years of
      follow-up period. The phenotypes and Kaplan-Meier event-free rates of the two
      groups were compared for cardiac events. This study investigated phenotypic
      severity in relation to the location of mutations in the protein sequence, which
      was analyzed using two sequence homology-based tools. In results, compound
      mutations in children were associated with a high incidence of syncope within the
      first decade (Group S: 32 % vs. Group C: 61 %), requiring an ICD in the second
      decade (Group S: 3 % vs. Group C: 56 %). Mortality in these patients was high
      within 5 years of birth (23 %). Phenotypic prediction tools correctly predicted
      the phenotypic severity in both Groups S and C, especially by using their
      coupling method. The coupling prediction method is useful in the initial
      evaluation of phenotypes both with single and compound mutations of LQTS
      patients. However, it should be noted that the compound mutation makes more
      severe phenotype. 

PMID- 27041097
TI  - Aortic Stiffness in Youth with Hypertrophic Cardiomyopathy Genotype.
AB  - Clinical events in hypertrophic cardiomyopathy (HCM) patients are related to the
      degree of hypertrophy. Aortic stiffness in adult HCM patients has been reported
      to be higher than control patients. Increased stiffness may cause more LV
      hypertrophy and thus lead to more clinical events. We sought to (a) noninvasively
      compare aortic structure and function between youth with sarcomeric HCM genotype
      versus control youth and (b) explore the relation between aortic function and
      degree of left ventricular (LV) hypertrophy. In a prospective study from a single
      referral center, clinical, anthropometric, and hemodynamic data were acquired on
      28 consecutive pathogenic HCM gene mutation carriers and 26 unrelated controls
      (mean age 16.3, 50 % girls). Hemodynamic data included applanation tonometry
      measured central pulse pressure, carotid-femoral pulse wave velocity (CFPWV),
      reflected wave augmentation index (AIx). In the HCM gene carriers, LV mass-to
      volume ratio was extracted from clinically indicated echocardiograms as an index
      of hypertrophy. Associations were assessed using multivariable adjusted linear
      regression. The HCM group was comprised of 14 myosin binding protein C3 carriers,
      13 myosin heavy chain 7 carriers, and 1 child with both. HCM and control groups
      did not differ by age, sex, height, body mass index, heart rate, or blood
      pressure. HCM carriers had significantly lower CFPWV than controls (4.46 +/- 0.88
      vs. 4.97 +/- 0.44 m/s, p = 0.01) and higher AIx magnitude (27 +/- 19 vs. 18 +/- 7
      %, p = 0.04). These associations persisted after adjustment for age, sex, height,
      heart rate, mean pressure, and medication use. Within the HCM group, LV
      hypertrophy was related to AIx but not CFPWV. CFPWV nor AIx differed by genotype.
      Aortic stiffness appears lower, but wave reflection appears higher in youth
      carrying HCM gene mutations. The degree of wave reflection appears correlated
      with LV hypertrophy in this high-risk cohort, suggesting that mitigation of wave
      reflection may possibly attenuate LV hypertrophy. 

PMID- 27041098
TI  - Blood Pool Segmentation Results in Superior Virtual Cardiac Models than
      Myocardial Segmentation for 3D Printing.
AB  - The method of cardiac magnetic resonance (CMR) three-dimensional (3D) image
      acquisition and post-processing which should be used to create optimal virtual
      models for 3D printing has not been studied systematically. Patients (n = 19) who
      had undergone CMR including both 3D balanced steady-state free precession (bSSFP)
      imaging and contrast-enhanced magnetic resonance angiography (MRA) were
      retrospectively identified. Post-processing for the creation of virtual 3D models
      involved using both myocardial (MS) and blood pool (BP) segmentation, resulting
      in four groups: Group 1-bSSFP/MS, Group 2-bSSFP/BP, Group 3-MRA/MS and Group 4
      MRA/BP. The models created were assessed by two raters for overall quality (1
      poor; 2-good; 3-excellent) and ability to identify predefined vessels (1-5:
      superior vena cava, inferior vena cava, main pulmonary artery, ascending aorta
      and at least one pulmonary vein). A total of 76 virtual models were created from
      19 patient CMR datasets. The mean overall quality scores for Raters 1/2 were 1.63
      +/- 0.50/1.26 +/- 0.45 for Group 1, 2.12 +/- 0.50/2.26 +/- 0.73 for Group 2, 1.74
      +/- 0.56/1.53 +/- 0.61 for Group 3 and 2.26 +/- 0.65/2.68 +/- 0.48 for Group 4.
      The numbers of identified vessels for Raters 1/2 were 4.11 +/- 1.32/4.05 +/- 1.31
      for Group 1, 4.90 +/- 0.46/4.95 +/- 0.23 for Group 2, 4.32 +/- 1.00/4.47 +/- 0.84
      for Group 3 and 4.74 +/- 0.56/4.63 +/- 0.49 for Group 4. Models created using BP
      segmentation (Groups 2 and 4) received significantly higher ratings than those
      created using MS for both overall quality and number of vessels visualized (p <
      0.05), regardless of the acquisition technique. There were no significant
      differences between Groups 1 and 3. The ratings for Raters 1 and 2 had good
      correlation for overall quality (ICC = 0.63) and excellent correlation for the
      total number of vessels visualized (ICC = 0.77). The intra-rater reliability was
      good for Rater A (ICC = 0.65). Three models were successfully printed on desktop
      3D printers with good quality and accurate representation of the virtual 3D
      models. We recommend using BP segmentation with either MRA or bSSFP source
      datasets to create virtual 3D models for 3D printing. Desktop 3D printers can
      offer good quality printed models with accurate representation of anatomic
      detail. 

PMID- 27041099
TI  - Three-dimensional Enhanced Imaging of Vitreoretinal Interface in Diabetic
      Retinopathy Using Swept-Source Optical Coherence Tomography.

PMID- 27041100
TI  - Inverted Internal Limiting Membrane Insertion for Macular Hole-Associated Retinal
      Detachment in High Myopia.

PMID- 27041101
TI  - Reply.

PMID- 27041102
TI  - Conjunctival Primary Acquired Melanosis: Is it Time for a New Terminology?

PMID- 27041103
TI  - Relationship Between Juxtapapillary Choroidal Volume and Beta-Zone Parapapillary
      Atrophy in Eyes With and Without Primary Open-Angle Glaucoma.

PMID- 27041104
TI  - Clinical Features and Outcomes of Retained Lens Fragments in the Anterior Chamber
      After Phacoemulsification.

PMID- 27041105
TI  - Species-specific real-time PCR assay for the detection of Streptococcus suis from
      clinical specimens.
AB  - A real-time polymerase chain reaction was developed to detect all known strains
      of Streptococcus suis. The assay was highly specific, and sensitivity was <10
      copies/assay for S. suis detection from clinical samples. 

PMID- 27041106
TI  - High-level carbapenem-resistant OXA-48-producing Klebsiella pneumoniae with a
      novel OmpK36 variant and low-level, carbapenem-resistant, non-porin-deficient,
      OXA-181-producing Escherichia coli from Thailand.
AB  - Five blaOXA-48-like-carrying Enterobacteriaceae isolates collected from two Thai
      patients in December 2012 were characterized. Three Klebsiella pneumoniae
      isolates giving two different pulsed-field gel electrophoresis patterns and
      sequence types (ST11 and ST37) from patient 1 harbored blaOXA-48 locating on
      Tn1999.2, whereas two Escherichia coli isolates with the same pulsotype and ST5
      from Patient 2 carried ISEcp1-associated blaOXA-181. One K. pneumoniae strain had
      blaSHV-12, blaDHA-1, qnrB, and qnrS, while another strain harbored blaCTX-M-15,
      qnrS and aac(6')-Ib-cr. The E. coli strain contained blaCTX-M-15, blaCMY-2, qnrS,
      and aac(6')-Ib-cr. Interestingly, the OXA-48 producers with a novel OmpK36
      variant by a substitution of Gly to Asp in the L3 loop-borne PEFXG motif
      exhibited high-level resistance to ertapenem, imipenem, and meropenem. In
      contrast, the OXA-181 producer with non-porin-deficient background showed low
      level resistance to ertapenem only. Both patients died because of either septic
      shock or pneumonia. This study showed the impact of OXA-48-like carbapenemases in
      porin-defective clinical isolate background, which may lead to serious
      therapeutic problems in the near future. 

PMID- 27041107
TI  - Is colistin effective in the treatment of infections caused by multidrug
      resistant (MDR) or extremely drug-resistant (XDR) gram-negative microorganisms in
      children?
AB  - The increasing incidence of infections caused by multidrug-resistant (MDR) or
      extremely drug-resistant (XDR) gram-negative organisms has led to the reemergence
      of colistin use. Clinical and demographic data were collected on 94 pediatric
      patients diagnosed with MDR or XDR gram-negative infections and treated with
      either a colistin-containing regimen (colistin group) or at least one
      antimicrobial agent other than colistin (noncolistin group). The overall clinical
      response rates were 65.8% in the colistin group and 70.0% in the noncolistin
      group (P = 0.33). The infection-related mortality rates were 11% in the colistin
      group and 13.3% in the noncolistin group (P = 0.74). There was no statistically
      significant difference in nephrotoxicity in the colistin and noncolistin groups.
      Colistin therapy was at least as effective and as safe as beta-lactam antibiotics
      or quinolones, with or without aminoglycosides, in the treatment of infections
      caused by gram-negative organisms and may be a therapeutic option in children. 

PMID- 27041108
TI  - Anagrelide and Mutational Status in Essential Thrombocythemia.
AB  - BACKGROUND: Anagrelide is an orally active, quinazolone-derived, platelet
      lowering agent that acts by blocking megakaryocyte maturation and
      polyploidization as well as proplatelet formation, and is currently indicated for
      second-line treatment of high-risk patients with essential thrombocythemia (ET)
      in Europe. In recent years various clinical trials have confirmed the safety and
      efficacy of this drug in ET, with some also considering Janus kinase 2 (JAK2)
      mutational status, but have not confirmed the impact that the other driver
      mutations, i.e., calreticulin (CALR) and myeloproliferative leukemia virus (MPL),
      may have on the response to this therapy. OBJECTIVE: To assess the impact of
      JAK2, MPL, CALR gene mutational status on response to anagrelide therapy in
      patients with ET treated at the Oncohematology Division, IRCCS Ca' Granda
      Maggiore Policlinico Hospital Foundation, Milan between 2004 and 2015. METHODS:
      Among 213 ET patients who were diagnosed between January 1983 to November 2014,
      21 consecutive cases who were started on anagrelide as a second-line therapy and
      received at least 1-year of treatment were included. Inclusion criteria were the
      availability of demographic, clinical, histological, and hematologic data at
      diagnosis, and at least one granulocyte DNA sample to assess the mutational
      status of the JAK2, MPL, and CALR genes. RESULTS: The JAK2V617F mutation was
      detected in seven patients (33.3 %), CALR mutations were identified in another
      seven cases, and the remaining seven patients were defined as "triple-negative"
      (i.e., no JAK2, CALR, or MPL mutation). After a median anagrelide treatment
      duration of 4.6 years, 16 of 21 patients (76.2 %) achieved at least a partial
      platelet response: in particular, the hematological response rate was
      substantially comparable between JAK2-positive and "triple-negative" patients,
      whereas the five patients who did not achieve any platelet response all had CALR
      mutations. CONCLUSION: Although it needs to be confirmed with a larger number of
      ET patients treated with anagrelide, we suggest that mutational status should be
      considered carefully when deciding on the most appropriate therapy for each
      patient, mainly because anagrelide alone was not able to achieve an appropriate
      hematological response in CALR-mutated ET cases.

PMID- 27041109
TI  - Postoperative endodontic pain of three different instrumentation techniques in
      asymptomatic necrotic mandibular molars with periapical lesion: a prospective,
      randomized, double-blind clinical trial.
AB  - OBJECTIVES: The purpose of this prospective, randomized, double-blind study was
      to compare postoperative pain of root canal treatment in patients with
      asymptomatic mandibular molar teeth with necrotic pulp and periapical lesion
      using three different instrumentation techniques: hand, multi-file rotary
      (ProTaper Universal), and reciprocating single-file (Wave-One) instrumentation
      techniques. MATERIALS AND METHODS: Ninety-six patients who fulfilled specific
      inclusion criteria were assigned to three groups according to the root canal
      instrumentation technique used: Hand (G1), ProTaper Universal (G2), and Wave-One
      (G3). One-visit root canal treatment was carried out, and the severity of the
      postoperative pain was assessed by the Heft-Parker visual analogue scale 6, 12,
      18, 24, 48, and 72 h after treatment. Data were analyzed by Kruskal-Wallis, chi
      2, Cochrane Q, one-way ANOVA, and Spearman's correlation analyses (alpha = 0.05).
      RESULTS: The patients in group 3 reported significantly lower postoperative pain
      levels at 6, 12, and 18 h compared with the patients in the two other groups (P <
      .05). In addition, the patients in group 2 reported significantly lower
      postoperative pain levels at 6 and 12 h compared with the patients in group 1 (P
      < .05). There were no significant differences in postoperative pain between the
      three groups at other time intervals (P > .05). The analgesic consumption was
      significantly higher in group 1 (P < .05), but no difference was seen between the
      two other groups (P > .05). CLINICAL RELEVANCE: Postoperative pain was
      significantly lower in patients undergoing root canal instrumentation with the
      Wave-One file compared with the ProTaper Universal and hand files.

PMID- 27041110
TI  - Prognostic factors in direct pulp capping with mineral trioxide aggregate or
      calcium hydroxide: 2- to 6-year follow-up.
AB  - OBJECTIVES: The aim of this retrospective study was to evaluate the influence of
      various predictors on healing outcomes after direct pulp capping (DPC) using
      either mineral trioxide aggregate (MTA) or calcium hydroxide (CH) as a pulp
      dressing agent. MATERIALS AND METHODS: The present study included 172 mature
      asymptomatic permanent teeth with carious-exposed pulp. The teeth were treated
      with DPC, using either MTA or CH, and the treatment outcome was evaluated
      clinically and radiographically. The effect of potential clinical variables on
      the treatment outcome of DPC was evaluated clinically and radiographically during
      a 24-72-month follow-up. In order to assess the cumulative successes of CH and
      MTA after DPC, Kaplan-Meier survival analysis and log-rank test was used. The
      subgroups were compared by means of the log-rank test. Also, univariate Cox
      regression analysis was used to determine hazard ratio of clinical variables.
      RESULTS: One hundred and fifty-two teeth of 172 capped teeth were available for
      follow-up, with an overall recall rate of 87.6 % for MTA vs 89.3 % for CH. The
      mean period of follow-up was 37.3 (+/-17.2) months. Overall success rates of 85.9
      and 77.6 % in the MTA and CH groups were observed, respectively. The cumulative
      success rate of both materials was not statistically different when analysed by
      the Cox proportional hazard regression analysis (P = 0.282). The Kaplan-Meier
      survival curves revealed that 2-year overall pulp survival was 91.4 %, while the
      4- and 6-year survival rates were 84 and 65 %, respectively. None of the clinical
      variables had a considerable influence on the outcome of DPC (p > 0.05).
      CONCLUSIONS: MTA-capped teeth demonstrated a slightly higher success rate than
      CH, revealing that it can be recommended as a reliable direct pulp-capping
      material. None of the clinical variables investigated significantly affected
      posttreatment healing. CLINICAL RELEVANCE: DPC with MTA is a straightforward
      procedure with favourable outcome of 24- to 72-month follow-ups in vital mature
      asymptomatic permanent teeth with cariously exposed pulp, and it may be
      considered a realistic alternative therapy to RCT.

PMID- 27041111
TI  - Soft tissue augmentation procedures at second-stage surgery: a systematic review.
AB  - OBJECTIVES: The aim of this systematic review was to evaluate the efficacy of
      different soft tissue augmentation/correction methods in terms of increasing the
      peri-implant width of keratinized mucosa (KM) and/or gain of soft tissue volume
      during second-stage surgery. MATERIALS AND METHODS: Screening of two databases,
      MEDLINE (PubMed) and EMBASE (OVID), and hand search of related articles, were
      performed. Human studies reporting on soft tissue augmentation/correction methods
      around submucosally osseointegrated implants during second-stage surgery up to
      July 31, 2015 were considered. Quality assessment of the selected full-text
      articles was performed according to the Cochrane collaboration's tool to assess
      the risk of bias. RESULTS: Overall, eight prospective studies (risk of bias:
      high) and two case series (risk of bias: high) were included. Depending on the
      surgical technique and graft material used, the enlargement of keratinized tissue
      (KT) ranged between -0.20 and 9.35 mm. An apically positioned partial-thickness
      flap/vestibuloplasty (APPTF/VP) in combination with a free gingival graft (FGG)
      or a xenogeneic graft material (XCM) was most effective. Applying a roll envelope
      flap (REF) or an APPTF in combination with a subepithelial connective tissue
      graft (SCTG), mean increases in soft tissue volumes of 2.41 and 3.10 mm,
      respectively, were achieved. Due to the heterogeneity of study designs, no meta
      analysis could be performed. CONCLUSIONS: Within the limitations of this review,
      regarding the enlargement of peri-implant KT, the APPTF in the maxilla and the
      APPTF/VP in combination with FGG or XCM in the lower and upper jaw seem to
      provide acceptable outcomes. To augment peri-implant soft tissue volume REF in
      the maxilla or APPTF + SCTG in the lower and upper jaw appear to be reliable
      treatment options. CLINICAL RELEVANCE: The localization in the jaw and the
      clinical situation are crucial for the decision which second-stage procedure
      should be applied.

PMID- 27041113
TI  - [In Process Citation].

PMID- 27041112
TI  - Long-Term Survivor with Intrathecal and Intravenous Trastuzumab Treatment in
      Metastatic Breast Cancer.
AB  - We report the case of a woman with metastatic breast cancer receiving intrathecal
      trastuzumab (and intravenous trastuzumab for more than 7 years). She was
      diagnosed in 2001 with a duct invasive breast cancer T3N1M0 HER2 (human epidermal
      growth factor receptor 2)-positive +++ HR (hormone receptor) -negative. She
      received chemotherapy and then she had a mastectomy. Several metastases were
      discovered and treated from 2003 to 2008 with chemotherapy. In March 2010, brain
      metastases and a leptomeningeal carcinomatosis from her HER2-positive breast
      cancer appeared. From that moment on she received intravenous trastuzumab (6
      mg/kg) every 3 weeks, intrathecal trastuzumab (21 mg) weekly for 16 injections
      and lapatinib. Intrathecal trastuzumab was stopped because of cerebrospinal fluid
      (CSF) clearing. Intrathecal trastuzumab was injected again from December 2013 for
      14 injections. The relevance of treating leptomeningeal carcinomatosis with
      intrathecal trastuzumab administration is shown through this case report.

PMID- 27041114
TI  - Does titanium in ionic form display a tissue-specific distribution?
AB  - Most studies have focused on the biodistribution of titanium(IV) oxide as
      nanoparticles or crystals in organism. But several reports suggested that
      titanium is released from implant in ionic form. Therefore, gaining insight into
      toxicokinetics of Ti ions will give valuable information, which may be useful
      when assessing the health risks of long-term exposure to titanium alloy implants
      in patients. A micro synchrotron radiation-induced X-ray fluorescence (u-SRXRF)
      was utilized to investigate the titanium distribution in the liver, spleen and
      kidneys of rats following single intravenous or 30-days oral administration of
      metal (6 mg Ti/b.w.) in ionic form. Titanium was mainly retained in kidneys after
      both intravenous and oral dosing, and also its compartmentalization in this organ
      was observed. Titanium in the liver was non-uniformly distributed-metal
      accumulated in single aggregates, and some of them were also enriched in calcium.
      Correlation analysis showed that metal did not displace essential elements, and
      in liver titanium strongly correlated with calcium. Two-dimensional maps of Ti
      distribution show that the location of the element is characteristic for the
      route of administration and time of exposure. We demonstrated that u-SRXRF can
      provide information on the distribution of titanium in internal structures of
      whole organs, which helps in enhancing our understanding of the mechanism of
      ionic titanium accumulation in the body. This is significant due to the
      popularity of titanium implants and the potential release of metal ions from them
      to the organism.

PMID- 27041115
TI  - Microdiversity of Echinococcus granulosus sensu stricto in Australia.
AB  - Echinococcus granulosus (sensu lato) is now recognized as an assemblage of
      cryptic species, which differ considerably in morphology, development, host
      specificity (including infectivity/pathogenicity for humans) and other aspects.
      One of these species, E. granulosus sensu stricto (s.s.), is now clearly
      identified as the principal agent causing cystic echinococcosis in humans.
      Previous studies of a small section of the cox1 and nadh1 genes identified two
      variants of E. granulosus s.s. to be present in Australia; however, no further
      work has been carried out to characterize the microdiversity of the parasite in
      its territory. We have analysed the sequence of the full length of the cox1 gene
      (1609 bp) from 37 isolates of E. granulosus from different hosts and geographic
      regions of Australia. The analysis shows that seven haplotypes of E. granulosus
      s.s. not previously described were found, together with five haplotypes known to
      be present in other parts of the world, including the haplotype EG01 which is
      widespread and present in all endemic regions. These data extend knowledge
      related to the geographical spread and host range of E. granulosus s.s. in a
      country such as Australia in which the parasite established around 200 years ago.

PMID- 27041116
TI  - Molecular genetic analysis in 93 patients and 193 family members with classical
      congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Croatia.
AB  - Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency is caused by
      mutation in the CYP21A2 gene. The frequency and spectrum of CYP21A2 mutations and
      genotype-phenotype correlations among different populations are variable. Aim of
      this study was to define mutation frequency and spectrum of CYP21A2 gene
      mutations in patients with classical 21-hydroxylase deficiency (21OHD) and their
      family members in Croatia and study genotype-phenotype correlation. Clinical
      features and mutations of CYP21A2 gene in 93 unrelated 21OHD patients and 193
      family members were examined. In this cohort, 66 patients were affected with salt
      wasting (SW) form, and 27 were affected with simple virilizing (SV) form of the
      disease. Mutations were identified in both alleles (67% compound heterozygous and
      33% homozygous) in 91 of 93 patients. Deletions and conversions were found in
      18.8% and point mutations in 79.6% alleles. Mutations in 3 alleles (1.6%)
      remained unidentified (in one patient we found only one, while in other no
      mutations were found at all). The most common point mutations were Intron 2
      splice mutation IVS2-13 A/C>G (35.5%) and p.R357W (16.7%). Genotypes were
      categorized into Groups 0, A, B and C according to the extent of enzyme
      impairment. Genotype-phenotype concordance was 100%, 85% and 75% for Groups 0, A
      and B, respectively. Since only classical 21OHD patients were studied, Group C
      comprised solely p.P31L mutation and had 73% patients with SV and 27% with SW
      phenotype. Intrafamilial phenotypic variability was found in two families.
      CYP21A2 genetic analysis in 193 family members showed that 126 parents were
      heterozygous carriers, 3 were newly discovered patients, 2 fathers were not
      biological parents, and mutations were not detected in 3. Among 59 siblings, 32
      were heterozygous carriers, 15 carried normal alleles, and 12 were patients (4
      newly diagnosed). Genotype-phenotype divergence observed in this study suggests
      caution in preconceptional counseling and prenatal diagnosis of CAH. High
      frequency of p.R357W mutation was found in Croatian patients with classical 21
      OHD. Genotyping of family members discovered new patients and thus avoided
      pitfalls in genetic counseling when the parents were found to be affected.

PMID- 27041117
TI  - Cell-based and in silico evidence against quercetin and structurally-related
      flavonols as activators of vitamin D receptor.
AB  - It has been reported that quercetin is an activator of rat vitamin D receptor
      (rVDR). However, the conclusion was based on experiments performed without all
      the appropriate control groups, raising the possibility of a false-positive
      finding. Furthermore, distinct differences exist in the chemical structures of
      quercetin and 1alpha,25-dihydroxyvitamin D3, which is a prototypic agonist of
      VDR. Therefore, we investigated systematically whether quercetin and other
      flavonols are agonists of rVDR, mouse VDR (mVDR), or human VDR (hVDR). Quercetin,
      3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin,
      tamarixetin, myricetin, and syringetin did not activate rVDR, mVDR, or hVDR in
      HEK-293 and HepG2 cells transfected with the corresponding receptor expression
      plasmid and either the secreted phosphoprotein 1 (Spp1) or cytochrome P450 24A1
      (CYP24A1) reporter plasmid, when compared to the respective empty vector control
      group transfected with one or the other reporter plasmid and treated with one of
      the flavonols. Control analysis indicated that lithocholic acid and 1alpha,25
      dihydroxyvitamin D3, but not rifampicin, activated rVDR, mVDR, and hVDR. As shown
      in transfected HEK293 and HepG2 cells, the flavonols did not influence hVDR
      ligand binding domain transactivation, steroid receptor coactivator-1
      recruitment, or hVDR target gene expression (transient receptor potential cation
      channel 6 and CYP24A1) in hVDR-expressing Caco-2 or LS180 cells. The cumulative
      data from the cell-based experiments were corroborated by results obtained from
      molecular docking analysis. In conclusion, quercetin, 3-hydroxyflavone, galangin,
      datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and
      syringetin are not agonists of rVDR, mVDR, or hVDR, as judged by cell-based and
      in silico evidence.

PMID- 27041118
TI  - 7-Ketocholesterol is increased in the plasma of X-ALD patients and induces
      peroxisomal modifications in microglial cells: Potential roles of 7
      ketocholesterol in the pathophysiology of X-ALD.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder induced by a mutation
      in the ABCD1 gene, which causes the accumulation of very long-chain fatty acids
      in tissue and plasma. Oxidative stress may be a hallmark of X-ALD. In the plasma
      of X-ALD patients with different forms of the disease, characterized by high
      levels of C24:0 and C26:0, we observed the presence of oxidative stress revealed
      by decreased levels of GSH, alpha-tocopherol, and docosahexaenoic acid (DHA). We
      showed that oxidative stress caused the oxidation of cholesterol and linoleic
      acid, leading to the formation of cholesterol oxide derivatives oxidized at C7 (7
      ketocholesterol (7KC), 7beta-hydroxycholesterol (7beta-OHC), and 7alpha
      hydroxycholesrol (7alpha-OHC)) and of 9- and 13-hydroxyoctadecadienoic acids (9
      HODE, 13-HODE), respectively. High levels of 7KC, 7beta-OHC, 7alpha-OHC, 9-HODE
      and 13-HODE were found. As 7KC induces oxidative stress, inflammation and cell
      death, which could play key roles in the development of X-ALD, the impact of 7KC
      on the peroxisomal status was determined in microglial BV-2 cells. Indeed,
      environmental stress factors such as 7KC could exacerbate peroxisomal
      dysfunctions in microglial cells and thus determine the progression of the
      disease. 7KC induces oxiapoptophagy in BV-2 cells: overproduction of H2O2 and O2
      , presence of cleaved caspase-3 and PARP, nuclear condensation and/or
      fragmentation; elevated [LC3-II/LC3-I] ratio, increased p62 levels. 7KC also
      induces several peroxisomal modifications: decreased Abcd1, Abcd2, Abcd3, Acox1
      and/or Mfp2 mRNA and protein levels, increased catalase activity and decreased
      Acox1-activity. However, the Pex14 level was unchanged. It is suggested that high
      levels of 7KC in X-ALD patients could foster generalized peroxisomal dysfunction
      in microglial cells, which could in turn intensify brain damage.

PMID- 27041119
TI  - Formation Mechanism of Flattened Top HFBI Domical Droplets.
AB  - A water droplet assumes a spherical shape because of its own surface tension.
      However, water droplets containing dissolved hydrophobin (HFBI) have flat
      surfaces. In our previous study, the mechanism of this unique phenomenon was
      revealed. HFBI forms a self-organized membrane that has a densely packed and
      honeycomb-like structure. Furthermore, the buckling strength of the membrane is
      higher than the surface tension of the HFBI droplet. Therefore, an HFBI domical
      droplet has a flat surface. However, it was not clear why only the top of the
      domical droplet was flattened while other areas such as the side face were not.
      In this study, we observed HFBI domical droplets to investigate this phenomenon.
      The flat top area (self-organized HFBI membrane) remained parallel to the ground
      even if the substrate was tilted. Therefore, buoyancy was thought to be a factor
      affecting the HFBI membrane. In addition, the side face of the HFBI domical
      droplet was analyzed by atomic force microscopy and electrochemical impedance
      spectroscopy, and it was found that the sides of the HFBI droplet were not
      composed of densely packed HFBI membranes.

PMID- 27041120
TI  - Health Implications of an Immigration Raid: Findings from a Latino Community in
      the Midwestern United States.
AB  - Immigration raids exemplify the reach of immigration law enforcement into the
      lives of Latino community members, yet little research characterizes the health
      effects of these raids. We examined the health implications of an immigration
      raid that resulted in multiple arrests and deportations and occurred midway
      through a community survey of a Latino population. We used linear regression
      following principal axis factoring to examine the influence of raid timing on
      immigration enforcement stress and self-rated health. We controlled for age, sex,
      relationship status, years in the county in which the raid occurred, children in
      the home, and nativity. 325 participants completed the survey before the raid and
      151 after. Completing the survey after the raid was associated with higher levels
      of immigration enforcement stress and lower self-rated health scores. Findings
      indicate the negative impact of immigration raids on Latino communities.
      Immigration discussions should include holistic assessments of health.

PMID- 27041121
TI  - Motivations of children and their parents to participate in drug research: a
      systematic review.
AB  - Information on motivations for research participation, may enable professionals
      to better tailor the process of recruitment and informed consent to the
      perspective of parents and children. Therefore, this systematic review assesses
      motivating and discouraging factors for children and their parents to decide to
      participate in clinical drug research. Studies were identified from searches in 6
      databases. Two independent reviewers screened and selected relevant articles.
      Results were aggregated and presented by use of qualitative metasummary. 38
      studies fulfilled the selection criteria and were of sufficient quality for
      inclusion in the qualitative metasummary. Most mentioned motivating factors for
      parents were: health benefit for child, altruism, trust in research, and relation
      to researcher. Most mentioned motivating factors for children were: personal
      health benefit, altruism and increasing comfort. Fear of risks, distrust in
      research, logistical aspects and disruption of daily life were mentioned most by
      parents as discouraging factors. Burden and disruption of daily life, feeling
      like a "guinea pig" and fear of risks were most mentioned as discouraging factors
      by children. CONCLUSION: Paying attention to these motivating and discouraging
      factors of children and their parents during the recruitment and informed consent
      process in drug research increases the moral and instrumental value of informed
      consent. WHAT IS KNOWN: * This systematic review pools the existing empirical
      literature on motivations of minors and their parents to consent or dissent to
      participation in clinical drug research. * The most mentioned motivating and
      discouraging factors for children and their parents to consent to participation
      in clinical drug research are identified aggregated and presented by use of
      qualitative metasummary. What is new: * This information can be used to adapt the
      research protocol, recruitment, and informed consent/assent process to the needs
      of children and their parents.

PMID- 27041122
TI  - Dietary diversity predicts dietary quality regardless of season in 6-12-month-old
      infants in south-west Ethiopia.
AB  - OBJECTIVE: Simple, cost-effective and convenient instruments like food group
      based scores are proposed to assess micronutrient adequacy of children in
      developing countries. We assessed the predictive ability and seasonal stability
      of a dietary diversity score (DDS) to indicate dietary quality of infants.
      DESIGN: A 24 h dietary recall assessment was carried out on a sample of 320 and
      312 breast-fed infants aged 6-12 months during harvest (HS) and pre-harvest (PHS)
      seasons, respectively, in Ethiopia. DDS was calculated based on seven food
      groups, while mean micronutrient density adequacy (MMDA) was calculated for eight
      micronutrients. Multiple linear regression models were used to assess the
      relationship between DDS and MMDA, and differences in nutrient intake between the
      two seasons. A receiver-operating characteristic curve analysis was performed to
      derive DDS cut-offs that maximized sensitivity and specificity of assessing
      dietary quality. SETTING: The study was conducted in the catchment of the Gilgel
      Gibe Field Research Centre of Jimma University, south-west Ethiopia. RESULTS: The
      mean (sd) DDS for HS and PHS was 2.1 (0.94) and 2.3 (1.1), respectively. The DDS
      was associated with MMDA (beta=0.045, P<0.0001 in HS; beta=0.044, P<0001 in PHS).
      A DDS of <=2 food groups best predicted 'low' MMDA (<50 %) with 84 % and 92 %
      sensitivity, 36 % and 43 % specificity, and 47 % and 51 % correct classification
      for the HS and PHS, respectively. CONCLUSIONS: DDS is predictive of dietary
      quality of breast-fed infants. The study supports the use of DDS to indicate
      inadequate intakes of micronutrients by breast-fed infants in different seasons.

PMID- 27041123
TI  - Development of a controlled release formulation by continuous twin screw
      granulation: Influence of process and formulation parameters.
AB  - The aim of this study was to evaluate the potential of twin screw granulation for
      the continuous production of controlled release formulations with
      hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate
      was included in the formulation as very water soluble model drug. A premix of
      metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60,
      w/w) was granulated with demineralized water via twin screw granulation. After
      oven drying and milling, tablets were produced on a rotary ModulTM P tablet
      press. A D-optimal design (29 experiments) was used to assess the influence of
      process (screw speed, throughput, barrel temperature and screw design) and
      formulation parameters (starch content of the filler) on the process (torque),
      granule (size distribution, shape, friability, density) and tablet (hardness,
      friability and dissolution) critical quality attributes. The torque was dominated
      by the number of kneading elements and throughput, whereas screw speed and
      filling degree only showed a minor influence on torque. Addition of screw mixing
      elements after a block of kneading elements improved the yield of the process
      before milling as it resulted in less oversized granules and also after milling
      as less fines were present. Temperature was also an important parameter to
      optimize as a higher temperature yielded less fines and positively influenced the
      aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable
      to that of immediate release formulations. Tensile strength and friability of
      tablets were not dependent on the process parameters. The use of starch as filler
      was not beneficial with regard to granule and tablet properties. Complete drug
      release was obtained after 16-20h and was independent of the design's parameters.

PMID- 27041124
TI  - Comparative evaluation of proliposomes and self micro-emulsifying drug delivery
      system for improved oral bioavailability of nisoldipine.
AB  - The objective of this study was to develop proliposomal formulation and self
      micro-emulsifying drug delivery system (SMEDDS) for a poorly bioavailable drug,
      nisoldipine and to compare their in vivo pharmacokinetics. Proliposomes were
      prepared by thin film hydration method using different lipids such as Soy
      phosphatidylcholine (SPC), Hydrogenated Soy phosphatidylcholine (HSPC),
      Dimyristoylphosphatidylcholine (DMPC) and Dimyristoyl phosphatidylglycerol sodium
      (DMPG), Distearyl phosphatidylcholine (DSPC), and Cholesterol in various ratios.
      SMEDDS formulations were prepared using varying concentrations of Capmul MCM,
      Labrasol, Cremophor EL and Tween 80. Both proliposomes and SMEDDS were evaluated
      for particle size, zeta potential, in vitro drug release, in vitro permeability
      and in vivo pharmacokinetics. In vitro drug release was carried out in purified
      water using USP type II dissolution apparatus. In vitro drug permeation was
      studied using parallel artificial membrane permeation assay (PAMPA) and everted
      rat intestinal perfusion techniques. In vivo pharmacokinetic studies were
      conducted in male Sprague-Dawley rats. Among the different formulations,
      proliposomes with drug:DMPC:cholesterol in the ratio of 1:2:0.5 and SMEDDS with
      Capmul MCM (13.04% w/w), Labrasol (36.96% w/w), Cremophor EL (34.78% w/w) and
      Tween 80 (15.22% w/w) demonstrated the desired particle size and zeta potential.
      Enhanced drug release was observed with proliposomes and SMEDDS compared to pure
      nisoldipine in purified water after 1h. Nisoldipine permeability across PAMPA and
      everted rat intestinal perfusion models was significantly higher with
      proliposomes and SMEDDS. Following single oral administration of proliposomes and
      SMEDDS, a relative bioavailability of 301.11% and 239.87% respectively, was
      achieved compared to pure nisoldipine suspension. 

PMID- 27041125
TI  - Application of a catenary PBPK model to predict the disposition of "catch and
      release" anti-PCSK9 antibodies.
AB  - The development of 'catch and release', or pH-sensitive, monoclonal antibodies
      (mAb) has become of interest to groups seeking to reduce the influence of target
      mediated elimination on pharmacokinetics and pharmacodynamics. In this work, a
      catenary physiologically-based pharmacokinetic (PBPK) model is described to
      predict the pharmacokinetic benefit conferred by engineering mAbs for 'catch and
      release' binding. Our previously published PBPK model was adapted for
      consideration of the production and elimination of proprotein convertase
      subtilisin/kexin type 9 (PCSK9) in mice, and the model was then applied to
      predict the pharmacokinetics of anti-PCSK9 mAb with pH-stable (J10) and pH
      sensitive binding (J17). The model was able to generate reasonable predictions of
      both J10 and J17 plasma pharmacokinetics. For J10, mean (+/-standard deviation)
      predicted vs. observed areas under the plasma concentration curve (AUCinf) were:
      217 (77.1) vs. 103nMday (1mg/kg), 1.14*10(3) (858) vs. 769nMday (3mg/kg), and
      6.60*10(3) (5.58*10(3)) vs. 2.86*10(3)nMday (10mg/kg), and for J17 the values
      were: 838 (161) vs. 818nMday (1mg/kg), 2.30*10(3) (441) vs. 2.57*10(3)nMday
      (3mg/kg), and 8.42*10(3) (1.50*10(3)) vs. 9.17*10(3)nMday (10mg/kg). Further
      simulations with the model predicted that target turnover and the magnitude of
      change in the complex dissociation rate constant between pH 7.4 and pH 6.0 are
      key determinants of the improvements in pharmacokinetics associated with 'catch
      and release' mAbs. The model described here may be useful for prediction of the
      pharmacokinetics of 'catch and release' mAbs directed against other targets. 

PMID- 27041126
TI  - Spatial distribution of oil depots monitored in human muscle using MRI.
AB  - Oil depots are parenteral drug formulations meant for sustained release of
      lipophilic compounds. According to mass transport models, the drug-release rate
      from these injections is determined by the surface area of the oil depot. Until
      now, the size of the surface area of injected depots has not been assessed,
      however. MRI provides an excellent possibility to distinguish between water and
      adipose tissue. The aim of this study was to investigate whether MRI can be used
      to determine the shape and hence the surface area of oil depots in muscle tissue.
      The developed MRI-scan protocol is demonstrated to be suitable for visualising
      oil depots. It was applied to determine the surface area of 0.5mL oil, i.m.
      injected in healthy volunteers. The mean (+/-RSD) surface area and volume of the
      depots recovered after injection was 755.4mm(2) (+/-26.5) and 520.1mm(3) (+/
      24.6). It is shown that the depot disappearance from the injection site is very
      variable between volunteers. It is suggested that the oil is first solubilized
      and subsequently distributed. In all cases, the oil was not detectable after
      14days. These factors are relevant for the understanding of the mechanism by
      which compounds are released out of oil depots. 

PMID- 27041127
TI  - Ethics and health promotion practice: exploring attitudes and practices in
      Western Australian health organisations.
AB  - Issue addressed Evidence-informed practice underpinned by ethics is fundamental
      to developing the science of health promotion. Knowledge and application of
      ethical principles are competencies required for health promotion practice.
      However, these competencies are often inconsistently understood and applied. This
      research explored attitudes, practices, enablers and barriers related to ethics
      in practice in Western Australian health organisations. Methods Semistructured,
      in-depth interviews were conducted with 10 health promotion practitioners,
      purposefully selected to provide a cross-section of government and non-government
      organisations. Interviews were recorded, transcribed and then themed. Results The
      majority of participants reported consideration of ethics in their practice;
      however, only half reported seeking Human Research Ethics Committee (HREC)
      approval for projects in the past 12 months. Enablers identified as supporting
      ethics in practice and disseminating findings included: support preparing ethics
      applications; resources and training about ethical practice; ability to access
      HRECs for ethics approval; and a supportive organisational culture. Barriers
      included: limited time; insufficient resourcing and capacity; ethics approval not
      seen as part of core business; and concerns about academic writing. Conclusion
      The majority of participants were aware of the importance of ethics in practice
      and the dissemination of findings. However, participants reported barriers to
      engaging in formal ethics processes and to publishing findings. So what?
      Alignment of evidence-informed and ethics-based practice is critical. Resources
      and information about ethics may be required to support practice and encourage
      dissemination of findings, including in the peer-reviewed literature.
      Investigating the role of community-based ethics boards may be valuable to
      bridging the ethics-evidence gap. 

PMID- 27041128
TI  - Isolation and Identification of an Antiproliferative Compound from Fructose
      Tryptophan Maillard Reaction Products.
AB  - This study was performed to isolate and identify a compound with
      antiproliferative activity against human stomach cancer cell lines, from fructose
      tryptophan Maillard reaction products (MRPs). The MRPs, prepared from a fructose
      tryptophan solution heated at 130  degrees C for 2 h, were fractionated into five
      solvent fractions: n-hexane, chloroform, ethyl acetate, butanol, and water. The
      highest antiproliferative activity was found in the chloroform fraction (85.93%
      at 200 MUg/mL), and the active compound from this chloroform fraction was
      purified by silica gel column chromatography, TLC, and preparative HPLC. The
      antiproliferative activity (IC50) of the active compound was 42.24 MUg/mL, and
      the active compound was identified as perlolyrine (C16H10N2O2) by (1)H/(13)C NMR,
      DEPT, HMBC, and LC-ESI-MS. Therefore, this research may be useful in developing
      perlolyrine as a functional therapeutic agent. 

PMID- 27041129
TI  - Label-Free Digital Quantification of Lipid Droplets in Single Cells by Stimulated
      Raman Microscopy on a Microfluidic Platform.
AB  - Quantitative characterization of a single-cell phenotype remains challenging. We
      combined a scalable microfluidic array of parallel cell culture chambers and
      stimulated Raman scattering (SRS) microscopy to quantitatively characterize the
      response of lipid droplet (LD) formation to free-fatty-acid stimuli with single
      LD resolution at the single-cell level. By enabling the systematic live-cell
      imaging with SRS microscopy in a microfluidic device, we were able to quantify
      the morphology of over a thousand live cells in 10 different chemical
      environments and with 8 replicates for each culture condition, in a single
      experiment, and without relying on fluorescent labeling. We developed an image
      processing pipeline for cell segmentation and LD morphology quantification using
      dual-channel SRS images. This allows us to construct distributions of the
      morphological parameters of LDs in the cellular population and expose the vast
      phenotypic heterogeneity among genetically similar cells. Specifically, this
      approach provides an analytical tool for quantitatively investigating LD
      morphology in live cells in situ. With this high-throughput, high-resolution, and
      label-free method, we found that LD growth dynamics showed considerable cell to
      cell variation. Lipid accumulation in nonadipocyte cells is mainly reflected in
      the increase of LD number, as opposed to an increase in their size or lipid
      concentration. Our method allows statistical single-cell quantification of the LD
      distribution for further investigation of lipid metabolism and dynamic behavior,
      and also extends the possibility to couple with other "omics" technologies in the
      future.

PMID- 27041130
TI  - Comparing Health Status, Health Trajectories and Use of Health and Social
      Services between Children with and without Developmental Disabilities: A
      Population-based Longitudinal Study in Manitoba.
AB  - BACKGROUND: Little information exists on health of children with developmental
      disabilities (DDs) in the Canadian province of Manitoba. METHOD: The present
      authors linked 12 years of administrative data and compared health status,
      changes in health and access to health and social services between children with
      (n = 1877) and without (n = 5661) DDs living in the province, matched by age, sex
      and region of residence. RESULTS: Children with DDs were significantly more
      likely than children in the matched comparison group to die before the age of 17
      and have a history of respiratory illness, diabetes and injury-related
      hospitalizations. Children with DD also had significantly higher average number
      of ambulatory physician visits and higher rate of continuity of care.
      CONCLUSIONS: Children with DDs had poorer health status than the matched
      comparison group. The health disparities experienced by children with DDs
      persisted over time. Further population-based longitudinal research is needed in
      this area.

PMID- 27041131
TI  - Postencephalitic epilepsy in children and adults: Etiology matters.

PMID- 27041132
TI  - Availability of antiepileptic drugs: Politicians' roles.

PMID- 27041133
TI  - In response: Postencephalitic epilepsy in children and adults: Etiology matters.

PMID- 27041134
TI  - In response: Postencephalitic epilepsy in children and adults: Etiology matters.

PMID- 27041135
TI  - Comment on outcome following multiple subpial transection in Landau-Kleffner
      syndrome and related regression.

PMID- 27041136
TI  - In response: Comment on outcome following multiple subpial transection in Landau
      Kleffner syndrome and related regression.

PMID- 27041137
TI  - Transcriptome sequencing reveals e-cigarette vapor and mainstream-smoke from
      tobacco cigarettes activate different gene expression profiles in human bronchial
      epithelial cells.
AB  - Electronic cigarettes (e-cigarettes) generate an aerosol vapor (e-vapor) thought
      to represent a less risky alternative to main stream smoke (MSS) of conventional
      tobacco cigarettes. RNA-seq analysis was used to examine the transcriptomes of
      differentiated human bronchial epithelial (HBE) cells exposed to air, MSS from
      1R5F tobacco reference cigarettes, and e-vapor with and without added nicotine in
      an in vitro air-liquid interface model for cellular exposure. Our results
      indicate that while e-vapor does not elicit many of the cell toxicity responses
      observed in MSS-exposed HBE cells, e-vapor exposure is not benign, but elicits
      discrete transcriptomic signatures with and without added nicotine. Among the
      cellular pathways with the most significantly enriched gene expression following
      e-vapor exposure are the phospholipid and fatty acid triacylglycerol metabolism
      pathways. Our data suggest that alterations in cellular glycerophopholipid
      biosynthesis are an important consequences of e-vapor exposure. Moreover, the
      presence of nicotine in e-vapor elicits a cellular response distinct from e-vapor
      alone including alterations of cytochrome P450 function, retinoid metabolism, and
      nicotine catabolism. These studies establish a baseline for future analysis of e
      vapor and e-vapor additives that will better inform the FDA and other
      governmental bodies in discussions of the risks and future regulation of these
      products. 

PMID- 27041138
TI  - The influence of drill length and irrigation system on heat production during
      osteotomy preparation for dental implants: an ex vivo study.
AB  - OBJECTIVE: This study aimed to measure the influence of drill length and
      irrigation system on heat production during osteotomy preparation for dental
      implants using bovine bone rib as experimental model. MATERIALS AND METHODS:
      Three groups were created: Group 1: drilling with three consecutive burs with
      double irrigation (internal and external) for a 4.0 mm conical implant; and Group
      2 and Group 3: drilling with three consecutive burs with external irrigation for
      a 4.1 mm cylindrical implant and for a 4.3 mm conical implant, respectively. Four
      lengths were tested: 10, 12, 14 and 16 mm; in site prepared on bovine ribs using
      a surgical unit linked to a testing device, to standardize and simulate implant
      drilling procedures. Bone temperature variations were recorded using three
      thermocouples in different positions as of the crestal bone: 2 mm, position (p1);
      7 mm, position 2 (p2); and 12 mm, position 3 (p3). RESULTS: The highest
      temperature changes were invariably recorded during the process of withdrawal.
      Significantly lower temperature changes (P < 0.02) could be recorded at maximum
      drilling depths during the shearing process regardless of drilling depth or
      irrigation method. Double irrigation was associated with significantly lower
      temperatures compared with external irrigation by the use of implant drills (P <
      0.01). CONCLUSIONS: Within the limitations of this ex vivo study was possible
      concluded that the use a double irrigation system in multiple conventional drill
      for osteotomy can decrease the heat generation when increase the drill length.

PMID- 27041140
TI  - Insertion length of airway exchange catheter during exchange of tracheal tube: a
      simulation study.

PMID- 27041139
TI  - The importance of immune evasion in the pathogenesis of rabies virus.
AB  - Rabies is a zoonotic disease caused by the Lyssavirus rabies virus (RABV) that
      can infect most mammals, including humans, where it has a case-fatality rate of
      almost 100%. Although preventable by vaccination, rabies causes c. 59,000 human
      fatalities every year worldwide. Thus, there exists an urgent need to establish
      an effective therapy and/or improve dissemination of vaccines for humans and
      animals. These outcomes require greater understanding of the mechanisms of RABV
      pathogenesis to identify new molecular targets for the development of
      therapeutics and/or live vaccines with high levels of safety. Importantly, a
      number of studies in recent years have indicated that RABV specifically
      suppresses host immunity through diverse mechanisms and that this is a key
      process in pathogenicity. Here, we review current understanding of immune
      modulation by RABV, with an emphasis on its significance to pathogenicity and the
      potential exploitation of this knowledge to develop new vaccines and antivirals. 

PMID- 27041141
TI  - Contraception After Kidney Transplantation, From Myth to Reality: A Comprehensive
      Review of the Current Evidence.
AB  - There is a misconception among transplant clinicians that contraception after a
      successful renal transplant is challenging. This is partly due to the complex
      nature of transplant patients, where immunosuppression and graft dysfunction
      create major concerns. In addition, good evidence regarding contraception and
      transplant is scarce, with most of the evidence extrapolated from observational
      and case-controlled studies, thus adding to the dilemma of treating these
      patients. In this review, we closely analyzed the different methods of
      contraception and critically evaluated the efficacy of the different options for
      contraception after kidney transplant. We conclude that contraception after renal
      transplant is successful with acceptable risk. A multidisciplinary team approach
      involving obstetricians and transplant clinicians to decide the appropriate
      timing for conception is recommended. Early counseling on contraception is
      important to reduce the risk of unplanned pregnancies, improve pregnancy
      outcomes, and reduce maternal complications in patients after kidney transplant.
      To ascertain appropriate advice on the method of contraception, individualizing
      the method of contraception according to a patient's individual risks and
      expectations is essential.

PMID- 27041142
TI  - Evaluation of unified intensity-modulated arc therapy for the radiotherapy of
      head-and-neck cancer.
AB  - PURPOSE: Recently our group developed a unified intensity-modulated arc therapy
      (UIMAT) technique which allows for the simultaneous inverse-optimization and the
      combined delivery of volume-modulated arc therapy (VMAT) and intensity-modulated
      radiation therapy (IMRT). The aim of this study was to evaluate the dosimetric
      benefits of UIMAT plans for radiation treatment of complex head-and-neck cancer
      cases. METHODS AND MATERIALS: A retrospective treatment planning study was
      performed on 30 head-and-neck cases, 15 of which were treated clinically with
      VMAT while the other 15 were treated with step-and-shoot IMRT. These cases were
      re-planned using our UIMAT technique and the results were compared with the
      clinically delivered plans. Plans were assessed in terms of clinically relevant
      metrics describing target volume coverage, dose conformity, and the sparing of
      organs at risk. RESULTS: When compared to stand-alone VMAT or IMRT, UIMAT plans
      offered slightly better tumor volume coverage (Median D95: 98.1% vs. 97.5%,
      p=0.01) and similar dose conformity (Median CI: 0.69 vs. 0.69, p=0.09). More
      significantly, UIMAT plans had substantially lower doses to all organs at risk,
      including the spinal cord (Median D2%: 29.9Gy vs. 35.6Gy, p<0.01), brainstem
      (Median D2%: 21.2Gy vs. 25.6Gy, p<0.01), left parotid (Median DMean: 26.1Gy vs.
      28.0Gy, p<0.01), and right parotid (Median DMean: 23.6Gy vs. 27.2Gy, p<0.01). The
      reduction in OAR doses did not result from the redistribution of dose to
      unspecified tissue. Furthermore, UIMAT plans can be delivered with comparable
      delivery times to VMAT (Median time: 135s vs. 168s, p=0.394) but with fewer
      monitor units (Median MU: 486 vs. 635, p<0.01). CONCLUSIONS: Compared to stand
      alone IMRT or VMAT, UIMAT was demonstrated to have a dosimetric advantage for the
      radiation treatment of head-and-neck cancer.

PMID- 27041143
TI  - A systematic study on Pt based, subnanometer-sized alloy cluster catalysts for
      alkane dehydrogenation: effects of intermetallic interaction.
AB  - Platinum-based bimetallic nanoparticles are analyzed by the application of
      density functional theory to a series of tetrahedral Pt3X cluster models, with
      element X taken from the P-block, preferably group 14, or from the D-block around
      group 10. Almost identical cluster geometries allow a systematic investigation of
      electronic effects induced by different elements X. Choosing the propane-to
      propene conversion as the desired dehydrogenation reaction, we provide estimates
      for the activity and selectivity of the various catalysts based on transition
      state theory. No significant Bronsted-Evans-Polanyi-relation could be found for
      the given reaction. A new descriptor, derived from an energy decomposition
      analysis, captures the effect of element X on the rate-determining step of the
      first hydrogen abstraction. Higher activities than obtained for pure Pt4 clusters
      are predicted for Pt alloys containing Ir, Sn, Ge and Si, with Pt3Ir showing
      particularly high selectivity. 

PMID- 27041146
TI  - When existence is not futile: The influence of mortality salience on the longer
      is-better effect.
AB  - This research examines how death reminders impact the valuation of objects of
      various ages. Building from the existence bias, the longer-is-better effect
      posits that which exists is good and that which has existed for longer is better.
      Integrating terror management theory, it was reasoned that mortality reminders
      fostering a motivation to at least symbolically transcend death would lead
      participants to evaluate older object more positively as they signal robustness
      of existence. Participants were reminded of death (vs. control) and evaluated
      new, 20-, or 100-year-old objects. Results indicated death reminders resulted in
      greater valuation of older objects. Findings are discussed with implications for
      terror management theory, the longer-is-better effect, ageism, materialism, and
      consumer behaviour. 

PMID- 27041147
TI  - Integration of ultrasound imaging into pre-clinical dental education.
AB  - INTRODUCTION: Patients have complex healthcare needs and typically require more
      than one healthcare discipline to address issues regarding their health.
      Interprofessional teams of healthcare professionals may be able to address these
      complex needs and improve patient outcomes by combining resources. To evaluate
      the feasibility of integrating ultrasound into a dental school curriculum to
      teach anatomy as part of an interprofessional education experience, the current
      study surveyed first-year dental students to determine their perceptions of the
      integration of ultrasound techniques into the curriculum. MATERIALS AND METHODS:
      Ultrasound laboratory exercises were developed for first-year dental students as
      part of their anatomy course. The exercises were focused on head, neck and
      abdominal anatomy. To assess student perception of the integration of ultrasound
      into the dental curriculum, a survey was created specifically for the current
      study. RESULTS: Between 2013 and 2015, two classes of first-year dental students
      participated in the ultrasound laboratory exercise and completed the survey (n =
      83). Student survey responses suggested ultrasound was a valuable teaching tool
      because it allowed them to visualise anatomical structures using live imaging.
      They also agreed that the ultrasound laboratory exercises were an efficient
      learning tool, but the majority did not believe that they would use ultrasound
      regularly in their future practice. CONCLUSIONS: Results of the current study
      suggested first-year dental students were satisfied with the integration of
      ultrasound techniques into the dental curriculum. Survey results indicated that
      the students enjoyed the ultrasound laboratory exercise and felt ultrasound was
      an effective learning tool.

PMID- 27041148
TI  - Lymphangioma Circumscriptum: Good Clinical Response to Isotretinoin Therapy.
AB  - Lymphangioma circumscriptum (LC) is a superficial form of lymphatic malformation
      that can be difficult to treat. Therapeutic approaches to LC such as laser
      therapy, sclerotherapy, and surgical excision give varying results. This is the
      first description of a case of LC successfully treated with oral isotretinoin.
      Further studies are needed to confirm whether this is a reproducible treatment
      option. 

PMID- 27041149
TI  - Bladder cancer diagnosis from bladder wash by Fourier transform infrared
      spectroscopy as a novel test for tumor recurrence.
AB  - This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more
      sensitive, rapid, non-destructive and operator-independent analytical diagnostic
      method for bladder cancer recurrence from bladder wash than other routinely used
      urine cytology and cystoscopy methods. A total of 136 patients were recruited.
      FTIR spectroscopic experiments were carried out as a blind study, the
      classification results of which were then compared with those of cytology and
      cystoscopy. Firstly, 71 samples (n = 37; bladder cancer and n = 34; control) were
      studied with transmittance FTIR spectroscopy. After achieving successful
      differentiation of the groups, to develop a more rapid diagnostic tool and check
      the reproducibility of the results, the work was continued with different samples
      (n = 65 as n = 44; bladder cancer and n = 21; control), using the reflection mode
      (ATR) of FTIR spectroscopy by a different operator. The results revealed
      significant alterations in moleculer content in the cancer group. Based on the
      spectral differences, using transmittance FTIR spectroscopy coupled with
      chemometrics, the diseased group was successfully differentiated from the
      control. When only carcinoma group was taken into consideration a sensitivity
      value of 100% was achieved. Similar results were also obtained by ATR-FTIR
      spectroscopy. This study shows the power of infrared spectroscopy in the
      diagnosis of bladder cancer.

PMID- 27041150
TI  - KCNQ1 mutations associated with Jervell and Lange-Nielsen syndrome and autosomal
      recessive Romano-Ward syndrome in India-expanding the spectrum of long QT
      syndrome type 1.
AB  - Long QT syndrome type 1 (LQT1) is the most common type of all Long QT syndromes
      (LQTS) and occurs due to mutations in KCNQ1. Biallelic mutations with deafness is
      called Jervell and Lange-Nielsen syndrome (JLNS) and without deafness is
      autosomal recessive Romano-Ward syndrome (AR RWS). In this prospective study, we
      report biallelic mutations in KCNQ1 in Indian patients with LQT1 syndrome. Forty
      patients with a clinical diagnosis of LQT1 syndrome were referred for molecular
      testing. Of these, 18 were excluded from the analysis as they did not fulfill the
      inclusion criteria of broad T wave ECG pattern of the study. Direct sequencing of
      KCNQ1 was performed in 22 unrelated probands, parents and at-risk family members.
      Mutations were identified in 17 patients, of which seven had heterozygous
      mutations and were excluded in this analysis. Biallelic mutations were identified
      in 10 patients. Five of 10 patients did not have deafness and were categorized as
      AR RWS, the rest being JLNS. Eight mutations identified in this study have not
      been reported in the literature and predicted to be pathogenic by in silico
      analysis. We hypothesize that the homozygous biallelic mutations identified in
      67% of families was due to endogamous marriages in the absence of consanguinity.
      This study presents biallelic gene mutations in KCNQ1 in Asian Indian patients
      with AR JLNS and RWS. It adds to the scant worldwide literature of mutation
      studies in AR RWS. (c) 2016 Wiley Periodicals, Inc.

PMID- 27041151
TI  - SnTox1, a Parastagonospora nodorum necrotrophic effector, is a dual-function
      protein that facilitates infection while protecting from wheat-produced
      chitinases.
AB  - SnTox1 induces programmed cell death and the up-regulation of pathogenesis
      related genes including chitinases. Additionally, SnTox1 has structural homology
      to several plant chitin-binding proteins. Therefore, we evaluated SnTox1 for
      chitin binding and localization. We transformed an avirulent strain of
      Parastagonospora nodorum as well as three nonpathogens of wheat (Triticum
      aestivum), including a necrotrophic pathogen of barley, a hemibiotrophic pathogen
      of sugar beet and a saprotroph, to evaluate the role of SnTox1 in infection and
      in protection from wheat chitinases. SnTox1 bound chitin and an SnTox1-green
      fluorescent fusion protein localized to the mycelial cell wall. Purified SnTox1
      induced necrosis in the absence of the pathogen when sprayed on the leaf surface
      and appeared to remain on the leaf surface while inducing both epidermal and
      mesophyll cell death. SnTox1 protected the different fungi from chitinase
      degradation. SnTox1 was sufficient to change the host range of a necrotrophic
      pathogen but not a hemibiotroph or saprotroph. Collectively, this work shows that
      SnTox1 probably interacts with a receptor on the outside of the cell to induce
      cell death to acquire nutrients, but SnTox1 accomplishes a second role in that it
      protects against one aspect of the defense response, namely the effects of wheat
      chitinases.

PMID- 27041152
TI  - Biomimetic catalysis of metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) have attracted great attention as a new type of
      prospective material with various merits and functionalities. MOFs can either act
      as biomimetic catalysts to mimic enzymatic activities or serve as hosts to
      encapsulate bio-active species for biomimetic catalysis. However, in comparison
      with the dramatic development of MOFs in other catalytic fields, MOF-based
      biomimetic catalysis is still in its infancy and is yet to be systematically and
      comprehensively explored. Herein, the principles and strategies for the design
      and synthesis of MOF-based biomimetic catalysts, especially the structural
      features of representative MOFs that are related to biomimetic catalysis, are
      summarized and reviewed. In addition, recent advances in biomimetic catalysis of
      MOFs and the relationships between their catalytic performances and the
      structural specificities are discussed in detail as well. 

PMID- 27041153
TI  - Clinical and radiological features of synchronous pure ground-glass nodules
      observed along with operable non-small cell lung cancer.
AB  - BACKGROUND: It is common to observe synchronous pure ground-glass nodules (PGN)
      along with operable primary tumor on initial CT scans while clinical and
      radiological features of these PGNs remain unclear. METHODS: We included patients
      with primary tumor and PGNs detected between June 2010 and December 2013
      retrospectively. The radiographic manifestations of all PGNs, pathologic findings
      of resected PGNs, and follow-up outcomes of unresected PGNs were analyzed to
      determine the predictors of malignant PGNs. RESULTS: Overall, 84 PGNs in 71
      patients were included, of which 41 were resected at primary surgery and 43 were
      followed up. In resected group, there were 17 carcinomatous PGNs, 11 atypical
      adenomatous hyperplasia, and 13 benign lesions. In a follow-up group, 7 out of 43
      PGNs grew, out of which four PGNs were diagnosed as adenocarcinoma and the
      remaining three PGNs were still followed up. In univariate analysis, size (P <
      0.001), air bronchogram (P = 0.001), bubble lucency (P = 0.038), and pleural tag
      (P = 0.004) were the factors for malignant potential of PGNs. Multivariate
      analysis showed that size was an independent risk factor (P = 0.005), and the cut
      off value was 9.4 mm. CONCLUSIONS: The initial size and imaging signs may be
      useful in assessing the malignant potential of synchronous PGNs before surgery.
      J. Surg. Oncol. 2016;113:738-744. (c) 2016 Wiley Periodicals, Inc.

PMID- 27041154
TI  - Interaction between Warfarin and Linezolid in Patients with Left Ventricular
      Assist System in Japan.
AB  - OBJECTIVE: The purpose of this study was to investigate the possible interaction
      between warfarin and linezolid in patients with a left ventricular assist system
      (LVAS) for the treatment of severe heart failure. METHODS: Patients with LVAS who
      were treated with linezolid for the treatment of infections from January 2003 to
      March 2013 were identified from medical records. The impact of linezolid on the
      clotting function, as well as the dose of warfarin during the first 10 days of
      linezolid therapy, was investigated. The mean prothrombin time-international
      normalized ratio (PT-INR) and mean doses of warfarin during 7 days before and 10
      days after the initiation of linezolid therapy were calculated for individual
      patients. The PT-INR per mg of WF dose on the previous day (X) was calculated.
      The warfarin dose, PT-INR, and warfarin sensitivity index (WSI) value before and
      after the initiation of linezolid were compared to evaluate the impact of
      linezolid on the effect of warfarin. RESULTS: Sixteen patients were enrolled in
      the study. Although the mean PT-INR increased from 3.74 to 4.06, no significant
      difference was observed (p=0.05). A significant difference was observed in the
      mean dose of warfarin before and after the initiation of linezolid
      administration, with a decrease from 3.23 to 2.69 mg/day (p=0.001). In contrast,
      the mean WSI value significantly increased from 1.37 to 1.82 (p=0.014). After 10
      days of linezolid administration, the mean X values increased over the baseline
      value by 31.7%. CONCLUSION: These findings suggest that co-administration of
      linezolid results in increased PT-INR in patients with LVAS treated with
      warfarin.

PMID- 27041155
TI  - Continuous Intravenous Morphine Infusion for Severe Dyspnea in Terminally Ill
      Interstitial Pneumonia Patients.
AB  - OBJECTIVE: The aims of this study were to evaluate the efficacy and safety of
      continuous morphine infusion for dyspnea in patients with acute exacerbation (AE)
      of end-stage interstitial pneumonia (IP). METHODS: We conducted a retrospective
      study. Based on the subjective clinical effectiveness ratings of "good,"
      "moderate," "poor," or "unknown," the efficacy of continuous morphine infusion
      treatment was evaluated as defined as symptom relief that was "good" or
      "moderate." PATIENTS: This study included 22 consecutive opioid-naive patients
      who received continuous morphine infusion in the palliative treatment of dyspnea
      resulting from AE-IP. RESULTS: Of 22 patients, nine achieved good dyspnea relief,
      eight had moderate relief, four had a poor response and one response was
      "unknown" within 24 hours of starting morphine infusion. Using an operational
      definition of dyspnea relief that was rated "good" or "moderate," the efficacy
      rate of morphine was 77% (n=17). There was a significant change in the
      respiratory rate (25 respirations per minute at baseline vs. 17 respirations per
      minute after 12 hours, p=0.02), however, none of the patients studied had fewer
      than eight respirations per minute. CONCLUSION: We conclude that continuous
      morphine infusion is an effective and safe therapy for severe dyspnea in terminal
      AE-IP patients without any serious adverse events.

PMID- 27041156
TI  - Clinical and Radiographic Comparison of Influenza Virus-associated Pneumonia
      among Three Viral Subtypes.
AB  - OBJECTIVE: Presently, the predominant subtypes of influenza viruses in the world,
      except for those in local epidemics, include influenza pandemic H1N1 2009
      (pH1N1), H3N2, and B viruses. There are few reports on the differences in the
      clinical features, radiographic findings, treatment, and outcomes of influenza
      virus-associated pneumonia among these three viral subtypes. The purpose of this
      study was to investigate whether the clinical features, radiographic findings,
      treatment, and outcomes differ among the viral subtypes. METHODS: We
      retrospectively analyzed 96 patients with influenza virus-associated pneumonia
      whose viral subtypes were clarified. RESULTS: Patients with pH1N1 virus
      associated pneumonia tended to be young. The frequency of primary viral pneumonia
      differed among the virus-associated pneumonia subtypes (pH1N1, 80%; H3N2, 26.5%;
      and B, 31%). Patients with pH1N1 virus-associated pneumonia more frequently
      showed bilateral ground-glass opacities (GGOs), which affected more lobes than in
      patients with H3N2 and B virus-associated pneumonia. However, patients with H3N2
      virus-associated pneumonia showed a higher frequency of consolidation and diffuse
      bronchial wall thickening than did the patients with pH1N1 virus-associated
      pneumonia. The severity and mortality did not differ among the three pneumonia
      subtypes. CONCLUSION: In the patients who developed influenza virus-associated
      pneumonia, those with pH1N1 virus-associated pneumonia frequently developed
      primary viral pneumonia resulting in bilateral and broad areas of GGOs on
      imaging, whereas patients with H3N2 virus-associated pneumonia frequently showed
      consolidation and diffuse bronchial wall thickening on pulmonary imaging.

PMID- 27041157
TI  - Post-Travel Consultations in a Regional Hub City Hospital, Japan.
AB  - OBJECTIVE: To clarify the characteristics of post-travel consultation services in
      Japan, particularly in the provinces, we analyzed our post-travel patients in the
      travel clinic of Kurume University Hospital located in Kurume City (a regional
      hub City in southwestern Japan). METHODS: Sixty post-travel patients visited our
      clinic between April 2008 and October 2014 and participated in this study: 55
      were Japanese and five were foreign. We summarized and compared the
      characteristics of the patients after dividing the Japanese participants into
      long-term travelers (>14 days) and short-term travelers (<=14 days). The foreign
      travelers were described in a separate analysis. RESULTS: Of the 55 Japanese
      travelers, the mean age (+/- standard deviation) was 37.3 +/- 16.3 years, and 36
      patients (65%) were men. Southeast Asia was the major destination (30/55, 55%),
      and business was stated as the major reason for travel (16/55, 29%). Post
      exposure rabies prophylaxis (16/55, 29%) was the most common purpose for the
      consultations. There were 34 participants (62%) who were classified as short-term
      travelers. Fewer of the short-term travelers stated receiving pre-travel
      consultations compared with long-term travelers (11% vs. 79%, p=0.0002). The five
      foreign travelers included one dengue fever patient and two malaria patients.
      CONCLUSION: Most post-travel Japanese patients visited our clinic were short-term
      travelers who had not received any pre-travel consultation. One of the most
      common complaints, post-exposure rabies prophylaxis, could have been avoided to
      some extent by appropriate pre-travel consultations. The results of this study
      suggest that pre-travel consultations should therefore be encouraged for both
      long- and short-term travelers.

PMID- 27041158
TI  - Early Gastric Cancer Recurrence Following Curative Resection Presenting as
      Biliary Tract Dilatation, Pancreatic Duct Dilatation and Intestinal Wall
      Thickening.
AB  - Early gastric cancer, especially cancer confined to the mucosa (stage T1a), is
      known to have a high cure rate with rare recurrence. We herein report the case of
      a 40-year-old female who initially presented with biliary tract dilatation,
      pancreatic duct dilatation and intestinal wall thickening 3 years after curative
      resection of pT1aN0 stage gastric cancer. The intestinal resection specimen
      revealed tumor cells spreading through the subserosa to the submucosa sparing
      mucosal membrane, which made exploratory laparotomy the only approach to confirm
      the diagnosis. It is always important to be aware of malignancy recurrence and
      clinicians should not hesitate to choose exploratory laparotomy to avoid any
      delay in the diagnosis and treatment. 

PMID- 27041159
TI  - Pathohistological Evidence of Smoldering Inflammation in Rheumatic Heart Disease
      with Massive Left Atrial Calcification.
AB  - A 74-year-old man, who had a history of a mitral valve replacement for rheumatic
      heart disease (RHD) 30 years previously, was admitted with progressive heart
      failure. Massive calcification was observed around the left atrium on
      multidetector CT, in addition to a late gadolinium enhancement (LGE)-positive
      layer adjacently outside of the calcification on MRI. He underwent a second
      mitral valve replacement for the prosthetic valve failure. Pathohistological
      analyses of a tissue section of the left atrial wall from a surgical specimen
      revealed lymphocyte and macrophage infiltration that coincided with the LGE
      positive layer on MRI, suggesting the existence of sustained active inflammation
      even after the long period of RHD. 

PMID- 27041160
TI  - Aortic Intimal Sarcoma Contributes to Atherosclerotic Renovascular Hypertension:
      An Autopsy Case Report and Review of the Literature.
AB  - An autopsy of a 70-year-old man with multiple bone metastases from a malignancy
      of unknown origin (MUO) and renovascular hypertension revealed an aortic intimal
      sarcoma (AIS) in the right renal artery accompanied by atherosclerotic changes.
      AIS appeared as aggregated mutton fat-like translucent particles arising from the
      intima of the branching portion of the right renal artery and was composed of
      undifferentiated, fine spindle cells with thicket-like proliferation. AIS was
      confirmed by immunohistopathology, showing the loss of the lumen lined by CD31
      positive endothelium and the expression of CD31, keratin, and vimentin in the
      viable part of the tumor. In patients with MUO presenting with both bone
      metastases and an acute or sub-acute onset of renovascular hypertension, AIS in
      the renal artery may be responsible. 

PMID- 27041161
TI  - The Evaluation of Adrenal Function in Two Cases of Hypocortisolism Accompanied by
      Liver Cirrhosis.
AB  - Adrenal insufficiency may occur in patients with liver cirrhosis. The assessment
      of hypothalamus-pituitary-adrenal function is important in such patients, but
      there is no consensus as to how it should be performed. We herein report the
      results of our evaluation of the adrenal function in two patients with
      hypocortisolism accompanied by liver cirrhosis. The patients lacked the typical
      features of hypocortisolism. One was diagnosed with hypocortisolism accompanied
      by liver cirrhosis while the other had secondary adrenal insufficiency caused by
      a hypothalamic disorder. Hypocortisolism accompanied by liver cirrhosis should be
      evaluated by endocrine tests to determine its pathogenesis. A low-dose
      adrenocorticotropic hormone test may be appropriate for non-critically ill
      cirrhotic patients. 

PMID- 27041162
TI  - The Long-term Effect of Adrenal Arterial Embolization for Unilateral Primary
      Aldosteronism on Cardiorenovascular Protection, Blood Pressure, and the
      Endocrinological Profile.
AB  - Primary aldosteronism (PA) is a major cause of secondary hypertension, divided
      into two subtypes: unilateral and bilateral. Unilateral PA (u-PA) is surgically
      curable. Medical treatment with mineralocorticoid receptors antagonists is
      recommended as a second-line treatment when the patients are not candidate for
      surgical treatment. The present case was a 39-year-old woman with u-PA, who had
      refused surgery, had suffered from adverse effects of medical treatment. She was
      treated with transcatheter adrenal arterial embolization (TAAE). Her blood
      pressure had been well controlled without progression of cardiorenovascular
      damage for 12 years. TAAE can be the third treatment option for u-PA patients. 

PMID- 27041163
TI  - A Fatal Case of Metformin-associated Lactic Acidosis.
AB  - A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the
      ER with metformin-associated lactic acidosis. She received continuous
      hemofiltration and hemodialysis, but the laboratory analyses showed no
      improvement. She died 11 hours after admission. Metformin is minimally bound to
      proteins and is readily dialyzable, but a prolonged period of dialysis is
      required, because metformin has a very large distribution volume and is
      distributed to multiple compartments. The peak blood metformin level was 432 mg/L
      in this case, which is one of the highest metformin concentrations ever reported,
      and eight hours of hemodialysis were not sufficient to reduce the serum level. 

PMID- 27041164
TI  - Brain Metastasis of Pleural Mesothelioma after a Subarachnoid Hemorrhage.
AB  - Malignant pleural mesothelioma (MPM) is an uncommon, fatal neoplasm induced by
      asbestos exposure. Brain metastases from MPM are extremely rare, with most such
      cases diagnosed only at the time of autopsy. This report describes what we
      believe to be the first case of MPM metastasizing to the brain after a
      subarachnoid hemorrhage, as well as the subsequent surgical removal of the brain
      metastasis. 

PMID- 27041165
TI  - Combined Pulmonary Fibrosis and Emphysema Preceding Lupus Pleuritis.
AB  - An 83-year-old man, who was a former smoker, with anti-ribonucleoprotein (RNP)
      antibody-positive combined pulmonary fibrosis and emphysema presented with a
      cough and dyspnea. A chest radiograph showed bilateral pleural effusions. His
      laboratory data showed proteinuria and elevated levels of anti-nuclear
      antibodies, anti-double strand DNA antibodies, and CA125, with decreased serum
      complement levels. Thoracentesis showed an exudative pleural effusion with an
      increased lymphocyte count and elevated CA125 levels. A thoracoscopic biopsy
      specimen showed proliferation of CA125-positive mesothelial cells. Systemic lupus
      erythematosus was diagnosed. His symptoms and pleural effusion resolved after the
      initiation of systemic corticosteroid therapy. The detection of anti-RNP antibody
      and CA125 levels are helpful in the diagnosis of lupus pleuritis. 

PMID- 27041166
TI  - Six Cases of Pulmonary Mycobacterium shinjukuense Infection at a Single Hospital.
AB  - Mycobacterium shinjukuense lung disease was diagnosed in 3 men and 3 women [mean
      age: 77.0+/-12.2 (57-93) years]. On imaging, 3 patients with previous pulmonary
      tuberculosis exhibited a fibrocavitary pattern, while the other 3 patients showed
      nodular bronchiectasis. A test with a tuberculosis rRNA identification kit (TRC
      Rapid((r)) M. TB) was falsely positive for M. tuberculosis due to DNA sequence
      similarity in 16SrRNA. M. shinjukuense was identified by the gene sequences of
      rpoB, 16S rRNA, and hsp65. The symptoms and imaging findings of most of the
      patients have improved with chemotherapy with low minimum inhibitory
      concentrations of anti-tuberculosis drugs. 

PMID- 27041167
TI  - Combined Allergic Bronchopulmonary Aspergillosis and Eosinophilic Granulomatosis
      with Polyangiitis: Three Cases and a Review of the Literature.
AB  - Previous reports of combined allergic bronchopulmonary mycosis (ABPM) and
      eosinophilic granulomatosis with polyangiitis (EGPA) are limited; however, among
      41 cases of ABPM and 18 cases of EGPA treated at our hospital, we experienced
      three cases of combined ABPM and EGPA. In two of these cases, the diagnosis of
      EGPA preceded that of ABPM, however, one of the two cases had already shown
      findings suggestive of ABPM, such as mucous plugs and central bronchiectasis, at
      the time of the diagnosis of EGPA. In six previously reported cases of combined
      ABPM and EGPA, ABPM preceded EGPA in four cases. In the other two cases in which
      EGPA was diagnosed before or simultaneously with ABPM, findings suggestive of
      ABPM had been detected when EGPA was diagnosed, which suggests that sensitization
      to fungi resulting in ABPM may play an important role in the development of EGPA.
      Careful attention should therefore be paid to the possibility that these diseases
      may coexist during the course of either disease. 

PMID- 27041168
TI  - Thymic Extranodal Marginal Zone Lymphoma of Mucosa-associated Lymphoid Tissue
      with 8q24 Abnormality.
AB  - Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT
      lymphoma) of the thymus is reported to have characteristic features that
      distinguish it from MALT lymphoma of other organs; it is proposed to be a
      distinct clinicopathological subgroup of MALT lymphoma. We herein present a case
      of thymic MALT lymphoma accompanied by Sjogren's syndrome, involving the first
      report of a thymic MALT lymphoma patient carrying a chromosomal abnormality of
      8q24. No c-myc gene translocation or c-Myc protein overexpression was observed,
      suggesting that c-myc was not involved in lymphomagenesis or progression.
      Although we did not examine the mechanisms by which the lymphoma developed, this
      chromosomal structural change in 8q24 may be associated with the pathogenesis in
      our case. 

PMID- 27041169
TI  - The Rapid Effectiveness of Minocycline against Scrub Typhus Meningoencephalitis.
AB  - Scrub typhus is associated with various clinical symptoms. However, the
      pathogenesis of scrub typhus infection remains to be elucidated. A 73-year-old
      man was admitted to our hospital with consciousness disturbance and suspected
      meningoencephalitis. The patient's laboratory data showed deterioration and were
      indicative of hemophagocytic lymphohistiocytosis (HLH). A whole body examination
      to detect the trigger disease revealed an eschar, which is a characteristic of
      scrub typhus, on his back. His symptoms showed dramatic improvement after the
      administration of minocycline (MINO). This case report highlights that the
      clinical course of a case of scrub typhus meningoencephalitis that was cured with
      MINO. 

PMID- 27041170
TI  - Intractable Neurosarcoidosis Effectively Treated with Infliximab.
AB  - We herein describe the case of an 18-year-old girl who presented with dizziness
      and headache in 2012. In 2013, brain magnetic resonance imaging revealed multiple
      intracerebral small lesions and intracerebral hydrocephalus. She was diagnosed
      with neurosarcoidosis following a brain biopsy. Although prednisolone,
      methotrexate, and azathioprine were administered, her hydrocephalus worsened and
      her granulomatous lesions were observed to increase in number on MRI. The
      patient's hydrocephalus showed no improvement despite her undergoing one
      ventriculoperitoneal shunt procedure, one septum pellucidum fenestration, and
      three ventriculoatrial shunt procedures. Infliximab therapy was then initiated,
      which resulted in a reduction in the size of the granulomatous lesions and the
      improvement of the patient's clinical symptoms. Infliximab may be a viable
      therapeutic option for treating intractable neurosarcoidosis. 

PMID- 27041171
TI  - Disappearance of the Hummingbird Sign after Shunt Surgery in a Case of Idiopathic
      Normal Pressure Hydrocephalus.
AB  - A 79-year-old man presented with a slowly progressive gait disturbance. Brain MRI
      demonstrated ventriculomegaly and the hummingbird sign. A lumbar puncture showed
      no abnormalities of the cerebrospinal fluid. The improvement of the gait
      disturbance after the ventriculoperitoneal shunt led to a diagnosis of idiopathic
      normal pressure hydrocephalus. Interestingly, postoperative brain MRI
      demonstrated the disappearance of not only ventriculomegaly, but also the
      hummingbird sign. The disappearance of the hummingbird sign suggests that an
      increase in the cerebrospinal fluid in the lateral and third ventricles could
      cause the compression of the superior surface of the midbrain tegmentum, which
      manifests as the hummingbird sign. 

PMID- 27041172
TI  - Recurrent Stenosis of the Ileum Caused by Rheumatoid Vasculitis.
AB  - A 65-year-old man with a 20-year history of rheumatoid arthritis was transferred
      to our hospital due to a second episode of intestinal obstruction, a fever, and
      joint pain within the previous 6 months. He had an extremely high rheumatoid
      factor level and decreased complement levels. Abdominal computed tomography, a
      small bowel series, and small intestinal endoscopy revealed severe ileal
      stenosis. Resection of the stenotic lesion was performed, and a histopathological
      examination revealed vasculitis. Rheumatoid vasculitis was diagnosed, and the
      patient began treatment with prednisolone and methotrexate, which improved his
      condition. Rheumatoid vasculitis is a rare, but possible cause of recurrent bowel
      obstruction. 

PMID- 27041173
TI  - Rice-Field Drowning-Associated Pneumonia in which Pseudomonas spp., Aspergillus
      fumigatus, and Cunninghamella sp. Are Isolated.
AB  - We herein report the case of an 84-year-old who developed pneumonia after
      drowning in a rice field. Besides Aspergillus fumigatus, many pathogens
      previously not reported in drowning-associated pneumonia (such as Pseudomonas
      fluorescens, Pseudomonas putida, Nocardia niigatensis, and Cunninghamella sp.)
      were isolated from his sputum. He received sulbactam/ampicillin,
      trimethoprim/sulfamethoxazole, voriconazole, levofloxacin and liposomal
      amphotericin B, but died due to respiratory failure. Because the patient had
      drowned in a contaminated stagnant rice field and had multiple lung cavities,
      zygomycosis was suspected. This report provides invaluable information for the
      consideration of zygomycosis after an individual drowning in a rice field, even
      in an immunocompetent patient. 

PMID- 27041174
TI  - Fatal Severe Fever with Thrombocytopenia Syndrome: An Autopsy Case Report.
AB  - As of June 2014, among six patients who had severe fever with thrombocytopenia
      syndrome (SFTS) at our hospital, an 83-year-old man died despite receiving
      appropriate critical care. An autopsy revealed extensive ischemic damage of the
      intra-abdominal organs, including the liver, spleen, stomach and gut, due to
      severe celiac atherosclerotic stenosis and superior mesenteric arterial
      thrombosis. Many SFTS virus nucleoprotein antigen-immunoreactive cells were
      detected in a paraaortic node, where necrotizing lymphadenitis was seen, and in
      the spleen. Fewer such cells were seen in the liver, bone marrow and adrenals.
      CONCLUSION: Atherosclerosis, in addition to hemophagocytic lymphohistiocytosis
      syndrome, can be lethal in elderly SFTS patients.

PMID- 27041175
TI  - Hypotension and Bradycardia Caused by the Inadvertent Ingestion of Rhododendron
      japonicum.
AB  - A 61-year-old man was transferred to our hospital with the complaints of
      dizziness, severe nausea and abdominal discomfort after consuming approximately
      50 g of the flowers of Rhododendron japonicum. On admission, hypotension and
      sinus bradycardia were evident. Symptoms including hypotension and bradycardia
      completely recovered within 12 hours following normal saline infusion and
      intravenous atropine. The ingestion of certain types of Rhododendron species can
      cause intoxication, referred to as "mad honey poisoning", due to the action of
      grayanotoxins. This is the first local case of acute intoxication caused by
      Rhododendron japonicum. 

PMID- 27041176
TI  - Three Times Repeated Portal Venous Gas after Meals.

PMID- 27041177
TI  - Idiopathic Internal Jugular Vein Thrombosis as Embolic Origin.

PMID- 27041178
TI  - Ruptured Aneurysm Associated with Bronchial Arteriovenous Malformation.

PMID- 27041179
TI  - MR Images in a Patient with Chronic Toluene Poisoning.

PMID- 27041180
TI  - Drug-induced Liver Injury with Human Herpesvirus (HHV)-6 Reactivation but without
      Exanthema or Fever.

PMID- 27041181
TI  - PSA ANNUAL MEETING 2008.

PMID- 27041182
TI  - MICROALGAE AND CYANOBACTERIA: FOOD FOR THOUGHT(1).
AB  - In non-Western civilizations, cyanobacteria have been part of the human diet for
      centuries. Today, microalgae and cyanobacteria are either produced in controlled
      cultivation processes or harvested from the natural habitats and marketed as food
      supplements around the world. Cyanobacteria produce a vast array of different
      biologically active compounds, some of which are expected to be used in drug
      development. The fact that some of the active components from cyanobacteria
      potentially have anticancer, antimicrobial, antiviral, anti-inflammatory, and
      other effects is being used for marketing purposes. However, introduction of
      these products in the form of whole biomass for alimentary purposes raises
      concerns regarding the potential toxicity and long-term effects on human health.
      Here, we review data on the use of cyanobacteria and microalgae in human
      nutrition and searched for available information on legislature that regulates
      the use of these products. We have found that, although the quality control of
      these products is most often self-regulated by the manufacturers, different
      governmental agencies are introducing strict regulations for placing novel
      products, such as algae and cyanobacteria, on the market. The existing
      regulations require these products to be tested for the presence of toxins, such
      as microcystin; however, other, sometimes novel, toxins remain undetected, and
      their long-term effects on human health remain unknown. 

PMID- 27041183
TI  - SEASONAL MODULE DYNAMICS IN SARGASSUM SUBREPANDUM (FUCALES, PHAEOPHYTA)(1).
AB  - Module dynamics of the fucoid alga SARGASSUM SUBREPANDUM (Forssk.) C. Agardh was
      studied in the southern Red Sea. Seasonal variation in thallus density and size
      was determined, and the initiation, growth, reproduction, and shedding of modules
      (primary laterals) were ascertained, using a tagging approach. Possible effects
      of different size-related parameters on module initiation, growth, reproduction,
      and shedding were analyzed in the context of contradicting results for other
      macroalgae, in comparison with terrestrial plants. Thallus density varied little;
      most of the seasonal variation occurred at the modular level. A restricted period
      of new module formation early in the cooler season was followed by fast growth
      and reproduction. Massive shedding of modules occurred toward the end of the
      cooler season leading to strongly reduced biomass in summer. There was some
      evidence that high module numbers inhibited new module formation and enhanced the
      maximum module elongation rate (fastest-growing module per thallus). On the other
      hand, elongation rates generally decreased, and apical tissue losses increased
      with increasing module length. This response was observed over a wide size range,
      suggesting grazing losses. There was no evidence of suppressed growth in small
      modules due to intraspecific competition. Elongation rates remained unaffected by
      reproductive status, indicating that there was no direct trade-off between growth
      and reproduction. Module survivorship was independent of module number and size,
      but fertile modules were more persistent than vegetative ones. We conclude that
      module dynamics are determined by seasonal changes in the environment, size
      dependent processes, and interactions among the modules. 

PMID- 27041184
TI  - PRESENCE OF ALGAE IN FRESHWATER ICE COVER OF FLUVIAL LAC SAINT-PIERRE (ST.
      LAWRENCE RIVER, CANADA)(1).
AB  - Winter ice cover is a fundamental feature of north temperate aquatic systems and
      is associated with the least productive months of the year. Here we describe a
      previously unknown freshwater habitat for algal and microbial communities in the
      ice cover of the freshwater St. Lawrence River, Quebec, Canada. Sampling
      performed during winter 2005 revealed the presence of viable algal cells, such as
      Aulacoseira islandica (O. Mull.) Simonsen (Bacillariophyceae), and microbial
      assemblage growing in the ice and at the ice-water interface. Vertical channels
      (1-5 mm wide) containing algae were also observed. Concentrations of chl a ranged
      between 0.5 and 169 MUg . L(-1) of melted ice, with maximal concentrations found
      in the lower part of the ice cores. These algae have the potential to survive
      when ice breakup occurs and reproduce rapidly in spring/summer conditions.
      Freshwater ice algae can thus contribute to in situ primary production,
      biodiversity, and annual carbon budget in various habitats of riverine
      communities. 

PMID- 27041185
TI  - CARBON SOURCE DEPENDENCE OF THE RATIO OF delta-AMINOLEVULINIC ACID BIOSYNTHESIS
      VIA THE C5 AND SHEMIN PATHWAYS IN EUGLENA GRACILIS (EUGLENOPHYCEAE)(1).
AB  - The ratio of two biosynthetic pathways was estimated, the C5 and Shemin pathways,
      to delta-aminolevulinic acid (ALA, a biosynthetic intermediate of tetrapyrrole)
      from the (13) C-enrichment ratios ((13) C-ER) at the carbon atoms of chl a (after
      conversion to methyl pheophorbide a) biosynthesized by Euglena gracilis G. A.
      Klebs when l-[3-(13) C]alanine was used as a carbon source. On the basis of these
      estimations, we confirmed that ALA was efficiently biosynthesized via both the C5
      and Shemin pathways in the plastids of E. gracilis, and we determined that the
      ratio of ALA biosynthesis via the Shemin pathway was increased in the ratio of
      14%-67%, compared with that in our previous d-[1-(13) C]glucose feeding
      experiment (Iida et al. 2002). This carbon source dependence of the contributions
      of the two biosynthetic pathways might be related to activation of
      gluconeogenesis by the amino acid substrate. The methoxy carbon of the
      methoxycarbonyl group at C-13(2) of chl a was labeled with the (13) C-carbon of l
      [methyl-(13) C]methionine derived from l-[3-(13) C]alanine via [2-(13) C]acetyl
      coenzyme A (CoA), through the atypical tricarboxylic acid (TCA) cycle,
      gluconeogenesis, and l-[3-(13) C]serine. The phytyl moiety of chl a was also
      labeled on C-P2, C-P3(1) , C-P4, C-P6, C-P7(1) , C-P8, C-P10, C-P11(1) , C-P12, C
      P14, C-P15(1) , and C-P16 from (13) C-isoprene (2-[1,2-methyl,3-(13) C3 ]methyl
      1,3-butadiene) generated from l-[3-(13) C]alanine via [2-(13) C]acetyl CoA. 

PMID- 27041186
TI  - IMPACT OF BLEACHING STRESS ON THE FUNCTION OF THE OXYGEN EVOLVING COMPLEX OF
      ZOOXANTHELLAE FROM SCLERACTINIAN CORALS(1).
AB  - Global climate change is leading to the rise of ocean temperatures and is
      triggering mass coral bleaching events on reefs around the world. The expulsion
      of the symbiotic dinoflagellate algae is believed to occur as a result of damage
      to the photosynthetic apparatus of these symbionts, although the specific site of
      initial impact is yet to be conclusively resolved. Here, the sensitivity of the
      oxygen evolving complex (OEC) to bleaching stress was studied as well as its
      natural variation between seasons. The artificial electron donor, diphenyl
      carbazide (DPC), was added to cultured, freshly isolated and expelled (bleaching
      treatments only) zooxanthellae suspensions. Chl a fluorescence and oxygen
      production measurements showed that upon addition of DPC, no restoration of
      diminished photochemical efficiency occurred under control or bleaching
      conditions. This result was consistent between 12 h and 5 d bleaching treatments
      on Pocilloporadamicornis, indicating that the OEC is not the primary site of
      damage, and that zooxanthellae expulsion from the host is a nonselective process
      with respect to the functioning of the OEC. Further experiments measuring fast
      induction curves (FICs) revealed that in both summer and winter, the temperature
      when OEC function was lost occurred between 7 degrees C and 14 degrees C above
      the sea surface temperature. FIC and oxygen production measurements of P.
      damicornis during exposure to bleaching stress demonstrated that the
      thermotolerance of the OEC increased above the temperature of the bleaching
      treatment over a 4 h period. This finding indicates that the OEC has the capacity
      to acclimate between seasons and remains functional at temperatures well above
      bleaching thresholds. 

PMID- 27041187
TI  - THE ROLE OF REACTIVE OXYGEN SPECIES IN COPPER TOXICITY TO TWO FRESHWATER GREEN
      ALGAE(1).
AB  - The role of reactive oxygen species (ROS) in copper (Cu) toxicity to two
      freshwater green algal species, Pseudokirchneriella subcapitata (Korshikov)
      Hindak and Chlorella vulgaris Beij., was assessed to gain a better mechanistic
      understanding of this toxicity. Cu-induced formation of ROS was investigated in
      the two algal species and linked to short-term effects on photosynthetic activity
      and to long-term effects on cell growth. A light- and time-dependent increase in
      ROS concentrations was observed upon exposure to environmentally relevant Cu
      concentrations of 50 and 250 nM and was comparable in both algal species.
      However, effects of 250 nM Cu on photosynthesis were different, leading to a 12%
      reduction in photosynthetic activity in P. subcapitata, but not in C. vulgaris.
      These results indicate that differences in species-specific sensitivities
      measured as photosynthetic activity were not caused by differences in the
      cellular ROS content of the algae, but probably by different species-specific ROS
      defense systems. To investigate the role of ROS in Cu-mediated inhibition of
      photosynthesis, the ROS scavenger N-tert-butyl-alpha-phenylnitrone (BPN) was
      used, resulting in a reduction of Cu-induced ROS production up to control level
      and a complete restoration of photosynthetic activity of Cu-exposed P.
      subcapitata. This finding implied that ROS play a primary role in Cu toxicity to
      algae. Furthermore, we observed a time-dependent ROS release process across the
      plasma membrane. More than 90% of total ROS were determined to be extracellular
      in P. subcapitata, indicating an efficient method of cellular protection against
      oxidative stress. 

PMID- 27041188
TI  - THE RELATIVE IMPORTANCE OF WATER MOTION ON NITROGEN UPTAKE BY THE SUBTIDAL
      MACROALGA ADAMSIELLA CHAUVINII (RHODOPHYTA) IN WINTER AND SUMMER(1).
AB  - The influence of seawater velocity (1.5-12 cm . s(-1) ) on inorganic nitrogen (N)
      uptake by the soft-sediment perennial macroalga Adamsiella chauvinii (Harv.) L.
      E. Phillips et W. A. Nelson (Rhodophyta) was determined seasonally by measuring
      uptake rate in a laboratory flume. Regardless of N tissue content, water velocity
      had no influence on NO3 (-) uptake in either winter or summer, indicating that
      NO3 (-) -uptake rate was biologically limited. However, when thalli were N
      limited, increasing water velocity increased NH4 (+) uptake, suggesting that mass
      transfer limitation of NH4 (+) is likely during summer for natural populations.
      Uptake kinetics (Vmax , Ks ) were similar among three populations of A. chauvinii
      at sites with different mean flow speeds; however, uptake rates of NO3 (-) and
      NH4 (+) were lower in summer (when N status was generally low) than in winter.
      Our results highlight how N uptake can be affected by seasonal changes in the
      physiology of a macroalga and that further investigation of N uptake of different
      macroalgae (red, brown, and green) during different seasons is important in
      determining the relative influence of water velocity on nutrient uptake. 

PMID- 27041189
TI  - IDENTIFICATION OF CROSS-FERTILIZED CONCHOCELIS USING CLEAVED AMPLIFIED
      POLYMORPHIC SEQUENCE MARKERS IN CROSS-EXPERIMENTS OF PORPHYRA YEZOENSIS
      (BANGIALES, RHODOPHYTA)(1).
AB  - As a part of the construction of a Porphyra yezoensis Ueda genetic linkage map,
      we conducted intraspecific cross-experiments and subsequent screening of cross
      fertilized conchocelis by cleaved amplified polymorphic sequence (CAPS) analysis.
      The cross-experiments were carried out between males of the wildtype (KGJ) and
      females of the recessive green mutant (TU-2) using two methods, controlled and
      random crosses. A total of 42 and 186 wildtype-colored conchocelis colonies were
      obtained from the former and latter experiments, respectively. Among those, 49
      DNA samples (14% and 23% obtained from the former and latter crosses,
      respectively) showed biparental CAPS patterns in the two gene regions (EF-1alpha
      open reading frame [ORF] region and V-ATPase). This study represents the first
      report in which the cross-fertilized conchocelis of P. yezoensis has been
      directly confirmed by molecular marker. The combination of the simple DNA
      extraction and CAPS analysis may be applicable in genetic studies of other
      macroalgae that are monoecious and/or grow slowly in laboratory culture. 

PMID- 27041190
TI  - INTER- AND INTRASPECIFIC RELATIONSHIPS BETWEEN NUCLEAR DNA CONTENT AND CELL SIZE
      IN SELECTED MEMBERS OF THE CENTRIC DIATOM GENUS THALASSIOSIRA
      (BACILLARIOPHYCEAE)(1).
AB  - The enormous species diversity of diatoms correlates with the remarkable range of
      cell sizes in this group. Nuclear DNA content relates fundamentally to cell
      volume in other eukaryotic cells. The relationship of cell volume to G1 DNA
      content was determined among selected members of the genus Thalassiosira, one of
      the most species-rich and well-studied centric diatom genera. Both minimum and
      maximum species-specific cell volume correlated positively with G1 DNA content.
      Phylogeny based on 5.8 S and ITS rDNA sequences indicated that multiple changes
      in G1 DNA content and cell volume occurred in Thalassiosira evolution, leading to
      a 1,000-fold range in both parameters in the group. Within the Thalassiosira
      weissflogii (Grunow) G. A. Fryxell et Grunow species complex, G1 DNA content
      varied 3-fold: differences related to geographic origin and time since isolation;
      doubling and tripling of G1 DNA content occurred since isolation in certain T.
      weissflogii isolates; and subcultures of T. weissflogii CCMP 1336 diverged in DNA
      content by 50% within 7 years of separation. Actin, beta-tubulin, and
      Spo11/TopVIA genes were selected for quantitative PCR estimation of haploid
      genome size in subclones of selected T. weissflogii isolates because they occur
      only once in the T. pseudonana Hasle et Heimdal genome. Comparison of haploid
      genome size estimates with G1 DNA content suggested that the most recent T.
      weissflogii isolate was diploid, whereas other T. weissflogii isolates appeared
      to be polyploid and/or aneuploid. Aberrant meiotic and mitotic cell divisions
      were observed, which might relate to polyploidization. The structural flexibility
      of diatom genomes has important implications for their evolutionary
      diversification and stability during laboratory maintenance. 

PMID- 27041191
TI  - AUTOGAMOUS AUXOSPORULATION IN PINNULARIA NODOSA (BACILLARIOPHYCEAE)(1).
AB  - Auxosporulation of the freshwater epipelic diatom Pinnularia nodosa (Ehrenb.) W.
      Sm. was studied in a clonal culture. Interphase cells possessed two chloroplasts
      with invaginated pyrenoids. The nucleus contained a single small body of
      heterochromatin at one end, also visible during most of meiotic prophase. During
      auxosporulation, induced by transfer of stationary-phase cells to fresh medium
      and suppressed by high nitrogen (N), an unpaired mother cell produced a single
      auxospore. Although meiosis II and nuclear fusion were not observed, indirect
      evidence indicated that auxosporulation was autogamous (rarely reported in
      pennate diatoms), rather than apomictic; paedogamy was excluded. The protoplast
      produced after meiosis either (1) matured into a "pseudozygote," via an
      asymmetrical contraction after meiosis I to form a single spherical cell at one
      end of the mother cell (pathway 1); or (2) constricted into two spherical cells
      (pathway 2). In pathway 2, the "pseudogametes" never fused and only one or none
      developed into a pseudozygote and then into an auxospore. Pathway 2 could be
      suppressed by continuous light. During metamorphosis of the spherical
      pseudozygote into an elongate young auxospore, a complete covering of thin
      siliceous incunabular strips was formed, separate from the organic wall formed
      around the pseudozygote when first formed and from the perizonium. Mature
      auxospores produced via pathway 2 had 60% of the volume as those produced via
      pathway 1 and had smaller chloroplasts (through loss of fragments during
      protoplast cleavage), but they achieved exactly the same lengths, suggesting that
      absolute length is monitored during expansion. 

PMID- 27041192
TI  - DIURNAL CELL DIVISION REGULATED BY GATING THE G1 /S TRANSITION IN ENTEROMORPHA
      COMPRESSA (CHLOROPHYTA)(1).
AB  - The cell-cycle progression of Enteromorpha compressa (L.) Nees (=Ulva compressa
      L.) was diurnally regulated by gating the G1 /S transition. When the gate was
      open, the cells were able to divide if they had attained a sufficient size.
      However, the cells were not able to divide while the gate was closed, even if the
      cells had attained sufficient size. The diurnal rhythm of cell division
      immediately disappeared when the thalli were transferred to continuous light or
      darkness. When the thalli were transferred to a shifted photoperiod, the rhythm
      of cell division immediately and accurately synchronized with the shifted
      photoperiod. These data support a gating-system model regulated by light:dark
      (L:D) cycles rather than an endogenous circadian clock. A dark phase of 6 h or
      longer was essential for gate closing, and a light phase of 14 h was required to
      renew cell division after a dark phase of >6 h. 

PMID- 27041193
TI  - ANALYSIS OF ANCIENT DNA FROM FOSSIL CORALLINES (CORALLINALES, RHODOPHYTA)(1).
AB  - The field of molecular paleontology has recently made significant contributions
      to anthropology and biology. Hundreds of ancient DNA studies have been published,
      but none has targeted fossil coralline algae. Using regions of the SSU gene, we
      analyzed rDNA from fossil coralline algae of varying ages and states of
      preservation from Spain, Papua New Guinea (PNG), and the Great Barrier Reef
      (GBR). Specimens from PNG, GBR, and some localities from Spain did not contain
      endogenous ancient DNA. Reproducible sequence data were obtained from specimens
      ~550 years old from near Cadiz, Spain, and from rocky-shore deposits in
      Carboneras, Almeria Province of Spain (~78,000 years before present [YBP]). Based
      on BLAST searches and a phylogenetic analysis of sequences, an undescribed
      coralline alga belonging to the Melobesioideae was discovered in the Carboneras
      material as well as the following coralline genera: Jania, Lithophyllum,
      Lithothamnion, Mesophyllum, and Phymatolithon. DNA from fleshy brown and red
      macroalgae was also discovered in the specimens from Carboneras. The coralline
      algae identified using molecular techniques were in agreement with those based on
      morphological methods. The identified taxa are common in the present-day
      southeastern Spain littoral zone. Amino acid racemization, concentration ratios,
      and specific concentrations failed to show a correlation between biomolecular
      preservation and PCR amplification success. Results suggest that molecular
      investigations on fossil algae, although limited by technical difficulties, are
      feasible. Validity of our results was established using authentication criteria
      and a self-critical approach to compliance. 

PMID- 27041194
TI  - PHYLOGENETIC RELATIONSHIPS WITHIN THE STYLONEMATALES (STYLONEMATOPHYCEAE,
      RHODOPHYTA): BIOGEOGRAPHIC PATTERNS DO NOT APPLY TO STYLONEMA ALSIDII(1).
AB  - The Stylonematales is the sole order of the Stylonematophyceae. The order
      consists of a mixture of filamentous or unicellular taxa that are small, grow on
      various surfaces, and are described from many floras, indicating that they may be
      cosmopolitan. Such ubiquity has been proposed to be due to properties of
      microorganisms, such as large population sizes, rather than human-derived
      phenomena. While their small nature makes most records fortuitous, we targeted
      these red algae to get a better understanding of their global distribution,
      genetic variation, and phylogeographic relationships. Our results indicated that
      the genera are mostly well supported, except for the position of Stylonema cornu
      cervi with Goniotrichopsis reniformis, while intergeneric relationships are
      mostly unsupported. The most commonly isolated species was Stylonema alsidii.
      Within this species, several well-supported clades were present. The
      phylogeographic relationships in S. alsidii showed no obvious biogeographic
      pattern, with supported clades containing samples from disparate locations, and
      multiple samples from the same area not grouping together. Some clades showed
      little genetic variation and wide distributions, possibly indicating human
      derived dispersal. Other clades, also with wide distribution, showed more genetic
      structure and could be candidates for groups formed by natural long-distance
      dispersal. While all issues on ubiquity cannot be answered with this data set, it
      would appear that at least S. alsidii is a true ubiquitous taxon. The sister
      relationship of Rufusia pilicola to the remaining Stylonematophyceae, the
      presence of the carbohydrate floridoside, and this species' unusual habitat
      indicate that it belongs to a new order, Rufusiales. 

PMID- 27041195
TI  - RESOLVING EVOLUTIONARY RELATIONSHIPS AMONG THE BROWN ALGAE USING CHLOROPLAST AND
      NUCLEAR GENES(1).
AB  - The brown algae are one of the largest and most important groups of primary
      producers in benthic coastal marine environments. Despite their biological
      importance, consensus regarding their taxonomic or evolutionary relationships
      remains elusive. Our goal was to produce a taxon-rich two-gene (rbcL and LSU
      rDNA) phylogeny. Key species were sequenced to represent each order and family in
      the analyses across all 19 orders and ~40 families, including selected outgroups
      Schizocladiophyceae and Xanthophyceae. Our results are in sharp contrast to
      traditional phylogenetic concepts; the Ectocarpales are not an early diverging
      clade, nor do the Fucales diverge early from other brown algae. Rather,
      Choristocarpus is sister to the remaining brown algae. Other groups traditionally
      considered to have primitive features are actually recently diverged lineages,
      turning traditional phylogenetic concepts upside down. Additionally, our results
      allow for the assessment, in the broadest context, of many of the historical and
      more recent taxonomic changes, resulting in several emended groups along with
      proposals for two new orders (Onslowiales, Nemodermatales) and one new family
      (Phaeosiphoniellaceae). 

PMID- 27041196
TI  - PHYLOGENY OF THE EUGLENOID LORICATE GENERA TRACHELOMONAS AND STROMBOMONAS
      (EUGLENOPHYTA) INFERRED FROM NUCLEAR SSU AND LSU rDNA(1).
AB  - Previous studies using the nuclear SSU rDNA and partial LSU rDNA have
      demonstrated that the euglenoid loricate taxa form a monophyletic clade within
      the photosynthetic euglenoid lineage. It was unclear, however, whether the
      loricate genera Trachelomonas and Strombomonas were monophyletic. In order to
      determine the relationships among the loricate taxa, SSU and LSU nuclear rDNA
      sequences were obtained for eight Strombomonas and 25 Trachelomonas strains and
      combined in a multigene phylogenetic analysis. Conserved regions of the aligned
      data set were used to generate maximum-likelihood (ML) and Bayesian phylogenies.
      Both methods recovered a strongly supported monophyletic loricate clade with
      Strombomonas and Trachelomonas species separated into two sister clades. Taxa in
      the genus Strombomonas sorted into three subclades. Within the genus
      Trachelomonas, five strongly supported subclades were recovered in all analyses.
      Key morphological features could be attributed to each of the subclades, with the
      major separation being that all of the spine-bearing taxa were located in two
      sister subclades, while the more rounded, spineless taxa formed the remaining
      three subclades. The separation of genera and subclades was supported by 42
      distinct molecular signatures (33 in Trachelomonas and nine in Strombomonas). The
      morphological and molecular data supported the retention of Trachelomonas and
      Strombomonas as separate loricate genera. 

PMID- 27041197
TI  - OLIGONUCLEOTIDE PRIMERS FOR THE DETECTION OF BIOLUMINESCENT DINOFLAGELLATES
      REVEAL NOVEL LUCIFERASE SEQUENCES AND INFORMATION ON THE MOLECULAR EVOLUTION OF
      THIS GENE(1).
AB  - Bioluminescence is reported in members of 18 dinoflagellate genera. Species of
      dinoflagellates are known to have different bioluminescent signatures, making it
      difficult to assess the presence of particular species in the water column using
      optical tools, particularly when bioluminescent populations are in nonbloom
      conditions. A "universal" oligonucleotide primer set, along with species and
      genus-specific primers specific to the luciferase gene were developed for the
      detection of bioluminescent dinoflagellates. These primers amplified luciferase
      sequences from bioluminescent dinoflagellate cultures and from environmental
      samples containing bioluminescent dinoflagellate populations. Novel luciferase
      sequences were obtained for strains of Alexandrium cf. catenella (Whedon et Kof.)
      Balech and Alexandrium fundyense Balech, and also from a strain of Gonyaulax
      spinifera (Clap. et Whitting) Diesing, which produces bioluminescence
      undetectable to the naked eye. The phylogeny of partial luciferase sequences
      revealed five significant clades of the dinoflagellate luciferase gene,
      suggesting divergence among some species and providing clues on their molecular
      evolution. We propose that the primers developed in this study will allow further
      detection of low-light-emitting bioluminescent dinoflagellate species and will
      have applications as robust indicators of dinoflagellate bioluminescence in
      natural water samples. 

PMID- 27041198
TI  - TIMING DEEP DIVERGENCE EVENTS IN CALCAREOUS DINOFLAGELLATES(1).
AB  - Based on morphological and molecular data, calcareous dinoflagellates
      (Thoracosphaeraceae, Peridiniales) are a monophyletic group comprising the three
      major clades Ensiculifera/Pentapharsodinium, Thoracosphaera/Pfiesteria, and
      Scrippsiella sensu lato. We used stratigraphically well-documented first
      occurrences of particular archeopyle types to constrain relaxed Bayesian
      molecular clocks applied to nuclear rRNA sequences of 18 representatives of the
      three main clades. By comparing divergence estimates obtained in differently
      calibrated clocks with first stratigraphic occurrences of taxa not themselves
      used as constraints, we identified plausible divergence times for several
      subclades of calcareous dinoflagellates. The initial diversification of extant
      calcareous dinoflagellates probably took place in the Late Jurassic, with the
      three main clades all established by the Cretaceous. The two mesoepicystal
      operculum types observed in calcareous dinoflagellates probably evolved
      independently from simple apical archeopyles. Based on our taxon sample, the K/T
      boundary had relatively little effect on the diversity of the group, with several
      lineages dating to before 65 mya (million years ago). The first stratigraphic
      occurrences of key taxa, such as Thoracosphaera and Calciodinellum (not
      themselves used as constraints), are in agreement with the molecular time
      estimates. Conflicts that involve "Calciodinellum"levantinum, Leonella,
      Pentapharsodinium, Pernambugia, and the Scrippsiella trochoidea species complex
      may be due to inaccurate assignment of fossils because of high morphological
      homoplasy and insufficient knowledge of the extant diversity of calcareous
      dinoflagellates. 

PMID- 27041199
TI  - NEW MARINE MEMBERS OF THE GENUS HEMISELMIS (CRYPTOMONADALES, CRYPTOPHYCEAE)(1).
AB  - Cryptomonads are a ubiquitous and diverse assemblage of aquatic flagellates. The
      relatively obscure genus Hemiselmis includes some of the smallest of these cells.
      This genus contained only two species until 1967, when Butcher described seven
      new marine species mainly on the basis of observations with the light microscope.
      However, from these seven taxa, only H. amylifera and H. oculata were validly
      published. Additionally, the features Butcher used to distinguish species have
      since been questioned, and the taxonomy within Hemiselmis has remained clouded
      due to the difficulty in unambiguously applying his classification and validating
      many of his species. As a result, marine strains are often placed into one of
      three species-H. rufescens Parke, H. virescens Droop, or the invalid H.
      brunnescens Butcher-based on cell color alone. Here we applied microscopic and
      molecular tools to 13 publicly available Hemiselmis strains in an effort to
      clarify species boundaries. SEM failed to provide sufficient morphological
      variation to distinguish species of Hemiselmis, and results from LM did not
      correlate with clades found using both molecular phylogenetic and nucleomorph
      genome karyotype analysis, indicating a high degree of morphological plasticity
      within species. On the basis of molecular characters and collection geography we
      recognize four new marine species of Hemiselmis-H. cryptochromatica sp. nov., H.
      andersenii sp. nov., H. pacifica sp. nov., and H. tepida sp. nov.-from the waters
      around North America. 

PMID- 27041200
TI  - MORPHOLOGY AND MOLECULAR PHYLOGENY OF A NEW MARINE SAND-DWELLING PROROCENTRUM
      SPECIES, P. TSAWWASSENENSE (DINOPHYCEAE, PROROCENTRALES), FROM BRITISH COLUMBIA,
      CANADA(1).
AB  - A new marine benthic, sand-dwelling Prorocentrum species from the temperate
      region of the Pacific coast of British Columbia, Canada, is described using LM
      and EM and molecular phylogenetic analyses. The cells have a broad oval shape,
      40.0-55.0 MUm long and 30.0-47.5 MUm wide, and a wide U-shaped periflagellar area
      on the right thecal plate. The left thecal plate consists of a straighter apical
      outline in the form of a raised ridge. Five to six delicate apical spines in the
      center of the periflagellar area are present. The nucleus is located in the
      posterior region of the cell, and a conspicuous pusule is located in the anterior
      region of the cell. The cells have golden-brown chloroplasts with a compound,
      intrachloroplast pyrenoid that lacks a starch sheath. The thecal plates are
      smooth with round pores of two different sizes. The larger pores are arranged in
      a specific pattern of radial rows that are evenly spaced around the plate
      periphery and of irregular rows (or double rows) that form an incomplete "V" at
      the apical end of the plates. Large pores are absent in the center of the left
      and right thecal plates. The intercalary band is striated transversely and also
      has faint horizontal striations. Trichocysts and two types of mucocysts are
      present. The molecular phylogenetic position of Prorocentrum tsawwassenense sp.
      nov. was inferred using SSU rDNA sequences. This new species branched with high
      support in a Prorocentrum clade containing both benthic and planktonic species. 

PMID- 27041201
TI  - PHYLOGENY OF THE CONJUGATING GREEN ALGAE BASED ON CHLOROPLAST AND MITOCHONDRIAL
      NUCLEOTIDE SEQUENCE DATA(1).
AB  - The conjugating green algae represent a lineage of charophyte green algae known
      for their structural diversity and unusual mode of sexual reproduction,
      conjugation. These algae are ubiquitous in freshwater environments, where they
      are often important primary producers, but few studies have investigated
      evolutionary relationships in a molecular systematic context. A 109-taxon data
      set consisting of three gene fragments (two from the chloroplast and one from the
      mitochondrial genome) was used to estimate the phylogeny of the genera of the
      conjugating green algae. Maximum likelihood (ML), maximum parsimony (MP), and
      Bayesian inference (BI) were used to estimate relationships from the 4,047
      alignable nucleotides. This study confirmed the polyphyly of the Zygnemataceae
      and Mesotaeniaceae with respect to one another. The Peniaceae were determined to
      be paraphyletic, and two genera traditionally classified among the Zygnematales
      appear to belong to the lineage that gave rise to the Desmidiales. Six genera,
      Euastrum, Cosmarium, Cylindrocystis, Mesotaenium, Spondylosium, and Staurodesmus,
      were polyphyletic in this analysis. These findings have important implications
      for the evolution of structural characteristics in the group and will require
      some taxonomic changes. More work will be required to delineate lineages of
      Zygnematales in particular and to identify structural synapomorphies for some of
      the newly identified clades. 

PMID- 27041202
TI  - PHYLOGENETIC POSITION AND MORPHOLOGY OF THECAE AND CYSTS OF SCRIPPSIELLA
      (DINOPHYCEAE) SPECIES IN THE EAST CHINA SEA(1).
AB  - Resting cysts of the marine phytoplanktonic dinoflagellate Scrippsiella spp. are
      encountered in coastal habitats and shallow seas all over the world.
      Identification of Scrippsiella species requires information on cyst morphology
      because the plate pattern of the flagellated cell is conserved. Cysts from
      sediments of the East China Sea were identified based on traits from both the
      cysts and the thecal patterns of germinated cells. Calcareous cysts belonged
      predominantly to S. trochoidea (F. Stein) A. R. Loebl., S. rotunda J. Lewis, and
      S. precaria Montresor et Zingone. The former two species also produced smooth and
      noncalcified cysts in the field. A new species, S. donghaienis H. Gu sp. nov, was
      obtained from six noncalcified cysts with organic spines. These cysts are
      spherical, full of pale white and greenish granules with a mesoepicystal
      archeopyle. The vegetative cells consist of a conical epitheca and a round
      hypotheca with a plate formula of po, x, 4', 3a, 7'', 6c (5c + t), 6 s, 5''',
      2'''' and are morphologically indistinguishable from S. trochoidea. Results of
      internal transcribed spacer (ITS) sequence comparisons revealed that S.
      donghaienis was distinct from the S. trochoidea complex and appeared nested
      within the Calciodinellum/Calcigonellum clade. Culture experiments showed that
      the presence of a red body in the cyst and the shape of the archeopyle were
      constant within cell lines from one generation to the next, while the
      morphological features of the cyst wall, such as calcification and spine shape,
      appeared to be phenotypically plastic. 

PMID- 27041203
TI  - THE EFFECTS OF HIGH IRRADIANCE ON THE SETTLEMENT COMPETENCY AND VIABILITY OF KELP
      ZOOSPORES(1).
AB  - Elevated irradiance has a profound effect on the successful dispersal and
      establishment of kelp zoospores, affecting their physiology and viability. The
      research to date, however, has been on zoospores localized near the benthos, with
      little attention on the importance of vertical transportation and subsequent
      exposure to increased irradiance. Therefore, we wanted to investigate the effects
      of exposure to high irradiance on the reproductive planktonic life-history stages
      of kelps Macrocystis pyrifera (L.) C. Agardh and Pterygophora californica Rupr.
      Zoospores of both species were exposed to different irradiances (75, 275, 575,
      1,025 MUmol photons . m(-2)  . s(-1) ) over varying durations (1, 2, 4, 8, 12 h)
      and subsequently monitored for settlement competency, gametophyte development,
      and reproductive viability. Settlement success for M. pyrifera was uniform
      throughout all irradiance * time treatments, while settlement for P. californica
      decreased with increasing exposure time but not irradiance, although settlement
      was generally reduced at the highest irradiance level. Following zoospore
      settlement, germ tube development was visible in the gametophytes of both species
      within 1 week, although a significant decline of germ tube density in P.
      californica was observed with increasing irradiance. Similarly, a decrease in
      germ tube development with increasing exposure was observed across all irradiance
      levels for M. pyrifera, but irradiance itself was not significant. Further
      development into embryonic sporophytes was remarkably similar to gametophyte
      development, suggesting that the effect of exposure of kelp zoospores to high
      irradiance on subsequent sporophyte production is mediated through gametophyte
      development as well as zoospore survival. 

PMID- 27041204
TI  - TEMPERATURE EFFECTS ON MICROALGAL PHOTOSYNTHESIS-LIGHT RESPONSES MEASURED BY O2
      PRODUCTION, PULSE-AMPLITUDE-MODULATED FLUORESCENCE, AND (14) C ASSIMILATION(1).
AB  - Short-term temperature effects on photosynthesis were investigated by measuring
      O2 production, PSII-fluorescence kinetics, and (14) C-incorporation rates in
      monocultures of the marine phytoplankton species Prorocentrum minimum (Pavill.)
      J. Schiller (Dinophyceae), Prymnesium parvum f. patelliferum (J. C. Green, D. J.
      Hibberd et Pienaar) A. Larsen (Coccolithophyceae), and Phaeodactylum tricornutum
      Bohlin (Bacillariophyceae), grown at 15 degrees C and 80 MUmol photons . m(-2)  .
      s(-1) . Photosynthesis versus irradiance curves were measured at seven
      temperatures (0 degrees C-30 degrees C) by all three approaches. The maximum
      photosynthetic rate (P(C) max ) was strongly stimulated by temperature, reached
      an optimum for Pro. minimum only (20 degrees C-25 degrees C), and showed a
      similar relative temperature response for the three applied methods, with Q10
      ranging from 1.7 to 3.5. The maximum light utilization coefficient (alpha(C) )
      was insensitive or decreased slightly with increasing temperature. Absolute rates
      of O2 production were calculated from pulse-amplitude-modulated (PAM) fluorometry
      measurements in combination with biooptical determination of absorbed quanta in
      PSII. The relationship between PAM-based O2 production and measured O2 production
      and (14) C assimilation showed a species-specific correlation, with 1.2-3.3 times
      higher absolute values of P(C) max and alpha(C) when calculated from PAM data for
      Pry. parvum and Ph. tricornutum but equivalent for Pro. minimum. The offset
      seemed to be temperature insensitive and could be explained by a lower quantum
      yield for O2 production than the theoretical maximum (due to Mehler-type
      reactions). Conclusively, the PAM technique can be used to study temperature
      responses of photosynthesis in microalgae when paying attention to the absorption
      properties in PSII. 

PMID- 27041205
TI  - DECREASE IN DYNAMIC VISCOSITY AND AVERAGE MOLECULAR WEIGHT OF ALGINATE FROM
      LAMINARIA DIGITATA DURING ALKALINE EXTRACTION(1).
AB  - Alginates are natural polysaccharides that are extracted from brown seaweeds and
      widely used for their rheological properties. The central step in the extraction
      protocol used in the alginate industry is the alkaline extraction, which requires
      several hours. In this study, a significant decrease in alginate dynamic
      viscosity was observed after 2 h of alkaline treatment. Intrinsic viscosity and
      average molecular weight of alginates from alkaline extractions 1-4 h in duration
      were determined, indicating depolymerization of alginates: average molecular
      weight decreased significantly during the extraction, falling by a factor of 5
      between 1 and 4 h of extraction. These results suggested that reducing extraction
      time could enable preserving the rheological properties of the extracted
      alginates. 

PMID- 27041206
TI  - APPLICATION OF THE PDMPO TECHNIQUE IN STUDYING SILICA DEPOSITION IN NATURAL
      POPULATIONS OF FRAGILARIA CROTONENSIS (BACILLARIOPHYCEAE) AT DIFFERENT DEPTHS IN
      A EUTROPHIC RESERVOIR(1).
AB  - At weekly intervals from July to October 2006, we measured silica deposition in
      the summer diatom assemblage at various depths in the eutrophic Rimov Reservoir
      (Czech Republic) using PDMPO, the 2-(4-pyridyl)-5{[4-(2-dimethylaminoethyl
      aminocarbamoyl)-methoxy]phenyl}oxazole labeling technique. Fluorescence
      microscopy coupled with image analysis allows quantifying silicon (Si) deposition
      over time and a simple distinction between cells that are actively depositing Si
      and those that are not. Diatom assemblage was exclusively dominated by Fragilaria
      crotonensis Kitton, which formed pronounced subsurface maxima (2-6.5 m).
      Concentrations of the main nutrients (Si and phosphorus, P) were low over the
      whole season; however, at depth, the nutrient availability was higher than at the
      surface. Fragilaria silica deposition rates were eight times higher at the
      surface than at depth. Half the population was involved in silica deposition at
      the surface, while only 20% active cells were doing so at depth. At the surface,
      silica deposition was limited by P deficiency; the effect of dissolved Si (DSi)
      was not statistically significant. Silica deposition at depth was significantly
      constrained by low light availability despite the 1% average light attenuation at
      depth, which is supposed sufficient for photosynthesis. This study represents the
      first attempt to employ the PDMPO technique coupled with quantitative image
      analysis of PDMPO fluorescence in freshwater ecology. On the basis of our
      results, PDMPO probe appears to be an appropriate proxy for the study of resource
      limitation in natural diatom populations. 

PMID- 27041207
TI  - SPATIAL HETEROGENEITY OF PHOTOSYNTHETIC ACTIVITY WITHIN DISEASED CORALS FROM THE
      GREAT BARRIER REEF(1).
AB  - Morphological diagnosis and descriptions of seven disease-like syndromes
      affecting scleractinian corals were characterized from the southern Great Barrier
      Reef (GBR). Chl a fluorescence of PSII was measured using an Imaging-PAM (pulse
      amplitude modulated) fluorometer, enabling visualization of the two-dimensional
      variability in the photophysiology of endosymbiotic dinoflagellates
      (zooxanthellae) by measuring rapid light curves. Three of four syndromes
      associated with active tissue loss (type a) were spatially homogenous (white
      syndrome, brown band, and skeletal eroding band), with no impact on the
      photochemical function of zooxanthellae populations at or behind the lesion
      borders. However, a decline in maximum quantum yield (Fv /Fm ) and elevated
      levels of maximum nonphotochemical quenching (NPQmax ) occurred in visually
      healthy tissue of black band disease adjacent to the lesion borders, possibly due
      to hypoxic conditions caused by the black band cyanobacterial mat. Two out of
      three syndromes associated with pathological change of intact tissue with no
      active tissue loss (type b) showed variable photophysiological responses
      (neoplasia and pigmentation response). Only the bleached foci associated with
      white patch syndrome appeared to impact primarily on the symbiotic
      dinoflagellates, as evidenced by declines in minimum fluorescence (F0 ) and
      maximum quantum yield (Fv /Fm ), with no indication of degeneration in the host
      tissues. Our results suggest that for the majority of coral syndromes from the
      GBR, pathogenesis occurs in the host tissue, while the impact on the
      zooxanthellae populations residing in affected corals is minimal. 

PMID- 27041208
TI  - Kidney cancer: AR promotes RCC via lncRNA interaction.

PMID- 27041209
TI  - Prostate cancer: Radiotherapy induces epigenetic changes.

PMID- 27041210
TI  - Tracking of Normal and Malignant Progenitor Cell Cycle Transit in a Defined
      Niche.
AB  - While implicated in therapeutic resistance, malignant progenitor cell cycle
      kinetics have been difficult to quantify in real-time. We developed an efficient
      lentiviral bicistronic fluorescent, ubiquitination-based cell cycle indicator
      reporter (Fucci2BL) to image live single progenitors on a defined niche coupled
      with cell cycle gene expression analysis. We have identified key differences in
      cell cycle regulatory gene expression and transit times between normal and
      chronic myeloid leukemia progenitors that may inform cancer stem cell eradication
      strategies. 

PMID- 27041211
TI  - Transition of phosphopantetheine adenylyltransferase from catalytic to allosteric
      state is characterized by ternary complex formation in Pseudomonas aeruginosa.
AB  - BACKGROUND: Phosphopantetheine adenylyltransferase (PPAT) is a rate limiting
      enzyme which catalyzes the conversion of ATP and pantetheine to dephosphocoenzyme
      and pyrophosphate. The enzyme is allosteric in nature and regulated by Coenzyme A
      (CoA) through feedback inhibition. So far, several structures have been solved to
      decipher the catalytic mechanism of this enzyme. METHODS: To address catalytic
      and inhibitory mechanisms of PPAT, structural insights from single crystal X-ray
      diffraction method were primarily used, followed by biophysical and biochemical
      analysis. RESULTS: We have solved the structures of PPAT from Pseudomonas
      aeruginosa with its substrate analogue AMP-PNP and inhibitor CoA. For the first
      time, a co-crystal structure of PPAT with Acetyl-CoA (AcCoA) was determined.
      Enzymatic analysis was performed to decipher the catalytic, allosteric and
      inhibitory mechanisms involved in regulation of PPAT. Binding affinities of PPAT
      with its substrates and inhibitors were determined by SPR. CONCLUSION: Previous
      studies from Escherichia coli and Arabidopsis indicated the inhibitory activity
      of AcCoA. PPAT-AcCoA structure along with some biochemical methods established
      AcCoA as an inhibitor to PPAT and illustrated its inhibitory mechanism.
      Transition from catalytic to allosteric state involves formation of ternary
      complex. We have studied the structural features of the ternary complex of PPAT
      along with its product pyrophosphate and inhibitor CoA and validated it with
      other biophysical and biochemical methods. Extensive analysis of all these 3D
      structures indicates that changes in side chains R90 and D94 are responsible for
      transition between catalytic and allosteric inhibitory states. GENERAL
      SIGNIFICANCE: These enzymatic studies provide new insights into the allosteric
      mechanism of PPAT.

PMID- 27041212
TI  - Structural architecture supports functional organization in the human aging brain
      at a regionwise and network level.
AB  - Functional interactions in the brain are constrained by the underlying anatomical
      architecture, and structural and functional networks share network features such
      as modularity. Accordingly, age-related changes of structural connectivity (SC)
      may be paralleled by changes in functional connectivity (FC). We provide a
      detailed qualitative and quantitative characterization of the SC-FC coupling in
      human aging as inferred from resting-state blood oxygen-level dependent
      functional magnetic resonance imaging and diffusion-weighted imaging in a sample
      of 47 adults with an age range of 18-82. We revealed that SC and FC decrease with
      age across most parts of the brain and there is a distinct age-dependency of
      regionwise SC-FC coupling and network-level SC-FC relations. A specific pattern
      of SC-FC coupling predicts age more reliably than does regionwise SC or FC alone
      (r = 0.73, 95% CI = [0.7093, 0.8522]). Hence, our data propose that regionwise SC
      FC coupling can be used to characterize brain changes in aging. Hum Brain Mapp
      37:2645-2661, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27041213
TI  - A novel fibroblast growth factor receptor 1 inhibitor protects against cartilage
      degradation in a murine model of osteoarthritis.
AB  - The attenuated degradation of articular cartilage by cartilage-specific deletion
      of fibroblast growth factor receptor 1 (FGFR1) in adult mice suggests that FGFR1
      is a potential target for treating osteoarthritis (OA). The goal of the current
      study was to investigate the effect of a novel non-ATP-competitive FGFR1
      inhibitor, G141, on the catabolic events in human articular chondrocytes and
      cartilage explants and on the progression of cartilage degradation in a murine
      model of OA. G141 was screened and identified via cell-free kinase-inhibition
      assay. In the in vitro study, G141 decreased the mRNA levels of catabolic markers
      ADAMTS-5 and MMP-13, the phosphorylation of Erk1/2, JNK and p38 MAPK, and the
      protein level of MMP-13 in human articular chondrocytes. In the ex vivo study,
      proteoglycan loss was markedly reduced in G141 treated human cartilage explants.
      For the in vivo study, intra-articular injection of G141 attenuated the surgical
      destabilization of the medial meniscus (DMM) induced cartilage destruction and
      chondrocyte hypertrophy and apoptosis in mice. Our data suggest that
      pharmacologically antagonize FGFR1 using G141 protects articular cartilage from
      osteoarthritic changes, and intra-articular injection of G141 is potentially an
      effective therapy to alleviate OA progression. 

PMID- 27041214
TI  - More from less: high-throughput dual polarity lipid imaging of biological
      tissues.
AB  - The high ion signals produced by many lipids in mass spectrometry imaging (MSI)
      make them an ideal molecular class to study compositional changes throughout
      tissue sections and their relationship with disease. However, the large extent of
      structural diversity observed in the lipidome means optimal ion signal for
      different lipid classes is often obtained in opposite polarities. In this work we
      demonstrate how new high speed MALDI-MSI technologies combined with precise laser
      position control enables the acquisition of positive and negative ion mode lipid
      data from the same tissue section much faster than is possible with other MSI
      instruments. Critically, using this approach we explicitly demonstrate how such
      dual polarity acquisitions provide more information regarding molecular
      composition and spatial distributions throughout biological tissues. For example,
      in applying this approach to the zebra finch songbird brain we reveal the high
      abundance of DHA containing phospholipids (PC in positive mode and PE, PS in
      negative ion mode) in the nuclei that control song learning behaviour. To make
      the most of dual polarity data from single tissues we have also developed a pLSA
      based multivariate analysis technique that includes both positive and negative
      ion data in the classification approach. In doing so the correlation amongst
      different lipid classes that ionise best in opposite polarities and contribute to
      certain spatial patterns within the tissue can be directly revealed. To
      demonstrate we apply this approach to studying the lipidomic changes throughout
      the tumor microenvironment within xenografts from a lung cancer model. 

PMID- 27041215
TI  - Case of subungual malignant melanoma showing the subtle clinical features and
      unexpected typical histopathological findings of melanoma in situ.

PMID- 27041216
TI  - Redox modulation of STIM-ORAI signaling.
AB  - STIM1 and ORAI1 constitute the core machinery of the ubiquitous store-operated
      calcium entry pathway and loss of function in these proteins is associated with
      severe immune and muscular disorders. Other isoforms-STIM1L, STIM2, ORAI2 and
      ORAI3 exhibit varied expression levels in different cell types along with several
      other interaction partners and thereby play different roles to facilitate,
      regulate and fine-tune the calcium entry. STIM proteins convey the Ca(2+) store
      depletion message to the PM and thereby participate in refilling of the ER by
      physically interacting with the Ca(2+)-selective ORAI channels at the PM. STIM
      and ORAI are exposed to oxidative modifications in the ER, the cytosol, and at
      the cell surface, and redox-mediated alterations in STIM/ORAI coupling might
      contribute to autoimmune disorders and cancer progression. This review discusses
      the redox reactivity of cysteine residues in STIM and ORAI isoforms, focusing on
      the oxidative modifications of STIM and ORAI proteins by which STIM-ORAI
      signaling can be modulated.

PMID- 27041217
TI  - mGluR-mediated calcium signalling in the thalamic reticular nucleus.
AB  - The thalamic reticular nucleus (TRN) plays a major role in modulating the
      transfer of information from the thalamus to the cortex. GABAergic inhibition via
      the TRN is differentially regulated by metabotropic glutamate receptors (mGluRs)
      and the effect of mGluRs on the membrane potential, on ion channels, and on the
      plasticity of electrical coupling of TRN neurons has been studied previously.
      Although mGluRs are generally known to trigger Ca(2+) transients, mGluR-mediated
      Ca(2+)-transients in TRN neurons have not yet been investigated. In this study,
      we show that mGluRs can trigger Ca(2+)-transients in TRN neurons, that these
      transients depend on intracellular Ca(2+)-stores, and are mediated by IP3
      receptors. Ca(2+) transients caused by the group I mGluR agonist DHPG elicit a
      current that is sensitive to flufenamic acid and has a reversal potential around 
      40mV. Our results add mGluR-mediated Ca(2+)-signalling in the TRN to the state
      dependent modulators of the thalamocortical system.

PMID- 27041218
TI  - Light-driven oxidation of polysaccharides by photosynthetic pigments and a
      metalloenzyme.
AB  - Oxidative processes are essential for the degradation of plant biomass. A class
      of powerful and widely distributed oxidative enzymes, the lytic polysaccharide
      monooxygenases (LPMOs), oxidize the most recalcitrant polysaccharides and require
      extracellular electron donors. Here we investigated the effect of using excited
      photosynthetic pigments as electron donors. LPMOs combined with pigments and
      reducing agents were exposed to light, which resulted in a never before seen 100
      fold increase in catalytic activity. In addition, LPMO substrate specificity was
      broadened to include both cellulose and hemicellulose. LPMO enzymes and pigment
      derivatives common in the environment of plant-degrading organisms thus form a
      highly reactive and stable light-driven system increasing the turnover rate and
      versatility of LPMOs. This light-driven system may find applications in
      biotechnology and chemical processing. 

PMID- 27041219
TI  - An open source cryostage and software analysis method for detection of antifreeze
      activity.
AB  - The aim of this study is to provide the reader with a simple setup that can
      detect antifreeze proteins (AFP) by inhibition of ice recrystallisation in very
      small sample sizes. This includes an open source cryostage, a method for
      preparing and loading samples as well as a software analysis method. The entire
      setup was tested using hyperactive AFP from the cerambycid beetle, Rhagium
      mordax. Samples containing AFP were compared to buffer samples, and the results
      are visualised as crystal radius evolution over time and in absolute change over
      30 min. Statistical analysis showed that samples containing AFP could reliably be
      told apart from controls after only two minutes of recrystallisation. The goal of
      providing a fast, cheap and easy method for detecting antifreeze proteins in
      solution was met, and further development of the system can be followed at
      https://github.com/pechano/cryostage.

PMID- 27041220
TI  - Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain
      Depend on the Ratio used in Combination in Rats.
AB  - Preclinical Research Neuropathic pain is particularly difficult to treat because
      of its diverse etiologies and underlying pathophysiological mechanisms. Drug
      combinations have been proposed to effectively treat some neuropathies. In the
      present study the interaction of five combinations of meloxicam and gabapentin,
      were studied to assess the possible synergistic antinociceptive response in
      neuropathic pain using the von Frey and acetone tests in rat models.
      Coadministration of meloxicam and gabapentin increased the antihyperalgesic or
      antiallodynic effects as compared with the compounds administered alone. The area
      under the curve (AUC) of the antihyperalgesic effects produced by the combination
      of the two drugs was generally similar to the theoretical sum of effects produced
      by each drug alone. However, the AUC of the antiallodynic effect produced by one
      combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the
      theoretical sum of the effects produced by each drug alone. The type of final
      interaction on the drug combinations can be additive or cause potentiation of
      antinociceptive effects and depends on the proportion of each compound used in
      dosing. Drug Dev Res 77 : 134-142, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27041221
TI  - A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer.
AB  - A deeper mechanistic understanding of tumour angiogenesis regulation is needed to
      improve current anti-angiogenic therapies. Here we present evidence from systems
      based miRNA analyses of large-scale patient data sets along with in vitro and in
      vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti
      angiogenic effect of miR-192 stems from its ability to globally downregulate
      angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR
      192 expression in human tumours is predictive of poor clinical outcome in several
      cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC)
      nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour
      angiogenesis in multiple ovarian and renal tumour models, resulting in tumour
      regression and growth inhibition. This anti-angiogenic and anti-tumour effect is
      more robust than that observed with an anti-VEGF antibody. Collectively, these
      data identify miR-192 as a central node in tumour angiogenesis and support the
      use of miR-192 in an anti-angiogenesis therapy. 

PMID- 27041222
TI  - Tibial component considerations in bicruciate-retaining total knee arthroplasty:
      A 3D MRI evaluation of proximal tibial anatomy.
AB  - BACKGROUND: Restoration of normal anatomy and proper ligament balance are
      theoretical prerequisites for reproducing physiological kinematics with
      bicruciate-retaining total knee arthroplasty (TKA). The purpose of this study was
      to use a 3D MRI technique to evaluate the topography of the proximal tibia and
      outline considerations in tibial component design for bicruciate-retaining TKA.
      METHODS: We identified 100 consecutive patients (50 males and 50 females) between
      ages 20 and 40 years with knee MRIs without arthritis, dysplasia, ACL tears, or
      prior knee surgery. A novel 3D MRI protocol coordinating axial, coronal, and
      sagittal images was used to measure: 1) medial and lateral posterior tibial
      slopes; 2) medial and lateral coronal slopes; and 3) distance from the anterior
      tibia to the ACL footprint. RESULTS: There was no overall difference in medial
      and lateral posterior tibial slopes (5.5 degrees  (95% CI 5.0 to 6.0 degrees )
      vs. 5.4 degrees  (95% CI 4.8 to 6.0 degrees ), respectively (p=0.80)), but 41
      patients had side-to-side differences greater than 3 degrees . The medial coronal
      slope was greater than the lateral coronal slope (4.6 degrees  (95% CI 4.0 to 5.1
      degrees ) vs. 3.3 degrees  (95% CI 2.9 to 3.7 degrees ), respectively
      (p<0.0001)). Females had less clearance between the anterior tibia and ACL
      footprint than males (10.8mm (95% CI 10.4 to 11.2mm) vs. 13.0mm (95% CI 12.5 to
      13.5mm), respectively (p<0.0001)). CONCLUSIONS: Due to highly variable proximal
      tibial topography, a monoblock bicruciate-retaining tibial baseplate may not
      reproduce normal anatomy in all patients. LEVEL OF EVIDENCE: Level IV - Anatomic
      research study.

PMID- 27041223
TI  - Unlinking an lncRNA from Its Associated cis Element.
AB  - Long non-coding (lnc) RNAs can regulate gene expression and protein functions.
      However, the proportion of lncRNAs with biological activities among the thousands
      expressed in mammalian cells is controversial. We studied Lockd (lncRNA
      downstream of Cdkn1b), a 434-nt polyadenylated lncRNA originating 4 kb 3' to the
      Cdkn1b gene. Deletion of the 25-kb Lockd locus reduced Cdkn1b transcription by
      approximately 70% in an erythroid cell line. In contrast, homozygous insertion of
      a polyadenylation cassette 80 bp downstream of the Lockd transcription start site
      reduced the entire lncRNA transcript level by >90% with no effect on Cdkn1b
      transcription. The Lockd promoter contains a DNase-hypersensitive site, binds
      numerous transcription factors, and physically associates with the Cdkn1b
      promoter in chromosomal conformation capture studies. Therefore, the Lockd gene
      positively regulates Cdkn1b transcription through an enhancer-like cis element,
      whereas the lncRNA itself is dispensable, which may be the case for other
      lncRNAs.

PMID- 27041224
TI  - Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems.
AB  - CRISPR-Cas adaptive immune systems in prokaryotes boast a diversity of protein
      families and mechanisms of action, where most systems rely on protospacer
      adjacent motifs (PAMs) for DNA target recognition. Here, we developed an in vivo,
      positive, and tunable screen termed PAM-SCANR (PAM screen achieved by NOT-gate
      repression) to elucidate functional PAMs as well as an interactive visualization
      scheme termed the PAM wheel to convey individual PAM sequences and their
      activities. PAM-SCANR and the PAM wheel identified known functional PAMs while
      revealing complex sequence-activity landscapes for the Bacillus halodurans I-C
      (Cascade), Escherichia coli I-E (Cascade), Streptococcus thermophilus II-A
      CRISPR1 (Cas9), and Francisella novicida V-A (Cpf1) systems. The PAM wheel was
      also readily applicable to existing high-throughput screens and garnered insights
      into SpyCas9 and SauCas9 PAM diversity. These tools offer powerful means of
      elucidating and visualizing functional PAMs toward accelerating our ability to
      understand and exploit the multitude of CRISPR-Cas systems in nature.

PMID- 27041225
TI  - CGG Repeat-Associated Non-AUG Translation Utilizes a Cap-Dependent Scanning
      Mechanism of Initiation to Produce Toxic Proteins.
AB  - Repeat-associated non-AUG (RAN) translation produces toxic polypeptides from
      nucleotide repeat expansions in the absence of an AUG start codon and contributes
      to neurodegenerative disorders such as ALS and fragile X-associated tremor/ataxia
      syndrome. How RAN translation occurs is unknown. Here we define the critical
      sequence and initiation factors that mediate CGG repeat RAN translation in the 5'
      leader of fragile X mRNA, FMR1. Our results reveal that CGG RAN translation is
      30%-40% as efficient as AUG-initiated translation, is m(7)G cap and eIF4E
      dependent, requires the eIF4A helicase, and is strongly influenced by repeat
      length. However, it displays a dichotomous requirement for initiation site
      selection between reading frames, with initiation in the +1 frame, but not the +2
      frame, occurring at near-cognate start codons upstream of the repeat. These data
      support a model in which RAN translation at CGG repeats uses cap-dependent
      ribosomal scanning, yet bypasses normal requirements for start codon selection.

PMID- 27041226
TI  - Pediatric appendicitis and need for antibiotics at time of discharge: Does route
      of administration matter?
AB  - INTRODUCTION: Following complicated appendicitis, there are limited data
      available to guide the surgeon regarding antibiotic selection, specifically in
      regards to route of administration. We hypothesized that among children with
      appendicitis who are discharged home with antibiotic therapy, the post-discharge
      readmission and complication rates do not differ between those children who
      receive IV antibiotics and those who receive PO antibiotics. METHODS: We
      performed a retrospective review of all children discharged home on antibiotics
      following appendectomy at a single institution between 11/10-10/14. We compared
      outcomes including ED and hospital readmission rates, and development of
      postoperative complications, between those children who were discharged on IV
      antibiotics and those discharged on PO antibiotics. RESULTS: 325 children were
      discharged with antibiotics following appendectomy (n=291 PO antibiotics group;
      n=34 IV group). On both univariate and multivariate analysis, rate of each
      complication did not differ between the two groups including inpatient
      readmission (5% PO vs. 6% IV; p=0.8), ED readmission (10% vs. 11%; p=0.8),
      postdischarge complications related to the operation (10% vs. 15%; p=0.4), or
      abscess development post-discharge (4% vs. 3%; p=1). CONCLUSIONS: Among children
      with complicated appendicitis who are discharged home with ongoing antibiotic
      therapy, our data demonstrate no differences in outcomes between those children
      who receive IV and PO antibiotics. Further data, collected in a prospective
      fashion, are needed to clarify the role of IV and PO antibiotics among children
      with perforated appendicitis.

PMID- 27041227
TI  - Decreased expression of miR-33 in fetal lungs of nitrofen-induced congenital
      diaphragmatic hernia rat model.
AB  - BACKGROUND: The pathogenesis of congenital diaphragmatic hernia (CDH) and the
      causes of pulmonary hypoplasia and hypertension remain unclear. miRNAs have been
      identified to play important regulatory roles in pulmonary pathological processes
      and lung development. We carried out the study to investigate the hypothesis that
      specific miRNAs are expressed differently in the lungs of nitrofen-induced rats,
      and to explore the possible targeting genes and roles of miR-33 in the
      pathological process of CDH. METHODS: Pregnant rats were divided into nitrofen
      and control group, and were exposed to nitrofen or vehicle respectively on D9.
      Fetuses were harvested on D21 and left lungs were dissected. 4 samples from each
      group underwent miRNAs microarray analysis using Agilent miRNA Array.
      Quantitative real-time polymerase chain reaction (qRT-PCR) was further performed
      to validate the miR-33 expression. RESULTS: 11 miRNAs exhibited increased
      expression in nitrofen group compared with control (p<0.05): miR-3588, miR-382*,
      miR-363, miR-375, miR-487b, miR-483, miR-382, miR-495, miR-434, miR-181a, and miR
      99a. 14 miRNAs showed decreased expression (p<0.05): miR-33, miR-193, miR-338,
      miR-30c-2*, miR-22, miR-18a, miR-532-5p, miR-28, miR-96, miR-551b, miR-141, miR
      362*, miR-30a*, and miR-3559-5p. Among them, miR-33 expression was markedly
      decreased in CDH lungs compared to controls and the result was confirmed by qRT
      PCR. CONCLUSION: Decreased expression of miR-33 was found in the nitrofen-induced
      hypoplastic lung on D21. This finding suggests that pathogenesis of lung
      hypoplasia and CDH in the nitrofen model involve epigenetic layer of regulation.

PMID- 27041228
TI  - A novel drainage technique during micropercutaneous nephrolithotomy in pediatric
      patients: double angiocath.
AB  - Micropercutaneous nephrolithotomy (microperc) is a recently introduced
      percutaneous nephrolithotomy (PNL) technique that has the smallest tract size.
      The absence of an amplatz sheath during the microperc technique is a fundamental
      difference that distinguishes it from all other types of PNL (standard, mini,
      ultramini). Increasing of the intrarenal pelvic pressure (IPP) was demonstrated
      by the authors in adult patients but this problem may be even more serious in
      pediatric patients. Previously, the authors defined the use of a 14 gauge
      angiocath needle and sheath (microsheath) during microperc surgery for pediatric
      patient to reduce the IPP. In this novel technique, a second angiocath is used to
      access the renal collecting system to drain fluid during surgery. This technique
      is more effective in reducing IPP during microperc, especially in pediatric
      patients. 

PMID- 27041229
TI  - Sentinel lymph node biopsy is a prognostic measure in pediatric melanoma.
AB  - BACKGROUND/PURPOSE: Sentinel lymph node biopsy (SLNB)-based management has been
      shown to improve disease-free survival in adult melanoma, but there is scant
      evidence regarding the utility of SLNB in pediatric melanoma. METHODS: The 2004
      2011 Surveillance, Epidemiology, and End Results database was queried for
      patients with primary cutaneous melanoma of Breslow depth>0.75mm and clinically
      negative nodes. Pediatric patients, defined as less than 20years of age, were
      grouped by whether they underwent SLNB or not. Kaplan-Meier analysis was
      performed to compare melanoma-specific survival (MSS) in propensity-matched
      groups. RESULTS: 310 pediatric patients met study criteria: 261 (84%) underwent
      SLNB, while 49 (16%) did not. There was no difference in MSS between matched
      children who received SLNB and those who did not (p=0.36). Among children who
      received SLNB, a positive SLNB was associated with worse MSS compared to a
      negative SLNB (89% vs. 100% at 84months, p=0.04). However, children with a
      positive SLNB had more favorable survival compared to patients >20years of age
      (88% vs. 66% at 84months, p=0.02). CONCLUSIONS: SLNB does not confer a survival
      benefit to children with melanoma, but it provides valuable prognostic
      information regarding MSS.

PMID- 27041230
TI  - The effect of bladder diverticula on bladder function: An experimental study in
      rabbits.
AB  - OBJECTIVE: This study aims to evaluate the effect of bladder diverticula (BD) on
      bladder function using a rabbit model, based on urodynamic findings. METHODS: A
      total of 32 New Zealand white rabbits were randomly assigned to four groups: (1)
      sham surgery; (2) a single, 1-cm-diameter BD; (3) a single, large, 3-cm-diameter
      BD; and (4) four (multi) 1-cm-diameter BD. Urodynamic evaluations were performed
      preoperatively, and 1week and 1month postoperatively, to measure the
      postmicturition residual (PMR), maximum bladder capacity (MBC), filling and
      voiding detrusor pressure (Pdet), compliance, and unstable detrusor contractions.
      At the end of the study, the animals were sacrificed and assessed for pathologic
      evaluation and stone formation. RESULTS: In groups 3 and 4, the rabbits all had
      PMR. At 30days postsurgery, the MBC was found to be 28% and 31% lower than the
      reference range in groups 3 and 4 and compliance was decreased (p<0.05). Further,
      the filling Pdet was significantly higher for large and multiple BD than in the 1
      cm diverticula or sham groups (6.33+/-1.73, 4+/-1.26, p=0.0001). Groups 3 (62%)
      and 4 (50%) had unstable detrusor contractions. There was also a
      muscular/collagen ratio increase in the large and multiple BD groups. Four
      rabbits in the large group and one rabbit in the multiple BD group exhibited
      stone formation. CONCLUSIONS: Large or multiple BD can alter bladder storage and
      emptying, and can decrease the capacity of the bladder and reduce its elasticity.
      Large or multiple bladder diverticula can lead to involuntary contractions,
      causing dysfunctional voiding.

PMID- 27041231
TI  - Genome instability: Linking ageing and brain degeneration.
AB  - Ageing is a multifactorial process affected by cumulative physiological changes
      resulting from stochastic processes combined with genetic factors, which together
      alter metabolic homeostasis. Genetic variation in maintenance of genome stability
      is emerging as an important determinant of ageing pace. Genome instability is
      also closely associated with a broad spectrum of conditions involving brain
      degeneration. Similarities and differences can be found between ageing-associated
      decline of brain functionality and the detrimental effect of genome instability
      on brain functionality and development. This review discusses these similarities
      and differences and highlights cell classes whose role in these processes might
      have been underestimated-glia and microglia.

PMID- 27041232
TI  - Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle
      insulin resistance through the Akt/AS160/GLUT4 pathway.
AB  - Insulin resistance of skeletal muscle plays an important role in the pathogenesis
      of type 2 diabetes. Galanin, a 29/30-amino-acid neuropeptide, plays multiple
      biological actions, including anti-diabetic effects. Although recent results of
      our study showed that administration of galanin could mitigate insulin resistance
      by promoting glucose transporter 4 (GLUT4) expression and translocation in
      skeletal muscle of rats, there is no literature available regarding to the effect
      of type 1 of galanin receptors (GALR1) on insulin resistance in skeletal muscle
      of type 2 diabetic rats. Herein, we intended to survey the central effect of
      GALR1 agonist M617 on insulin resistance in skeletal muscle and its underlying
      mechanisms. We found that the intracerebroventricular injection of M617 increased
      glucose infusion rates in hyperinsulinemic euglycemic clamp tests, but attenuated
      the plasma insulin and glucose concentrations of diabetic rats. Furthermore,
      administration of M617 markedly increased GLUT4 mRNA expression and GLUT4
      translocation in skeletal muscle of diabetic rats. Last, perfusion of M617
      increased phosphorylated Akt and phosphorylated AS160 levels in the skeletal
      muscle of diabetic rats. In conclusion, central injection of M617 mitigated
      insulin resistance of skeletal muscle by enhancing GLUT4 translocation from
      intracellular pools to plasma membranes via the activation of the Akt/AS160/GLUT4
      signaling pathway.

PMID- 27041233
TI  - Sharing the Love.

PMID- 27041234
TI  - Subcellular calcium dynamics during juvenile development in mouse hippocampal
      astrocytes.
AB  - Astrocytes generate calcium signals throughout their fine processes, which are
      assumed to locally regulate neighbouring neurotransmission and blood flow. The
      intercellular morphological relationships mature during juvenile periods when
      astrocytes elongate highly ramified processes. In this study, we examined
      developmental changes in calcium activity patterns of single hippocampal
      astrocytes using a transgenic mouse line in which astrocytes selectively express
      a genetically encoded calcium indicator, Yellow Cameleon-Nano50. Compared with
      postnatal day 7, astrocytes at postnatal day 30 showed larger subcellular calcium
      events and a greater proportion of somatic events. At both ages, the calcium
      activity was abolished by removal of extracellular calcium ions. Calcium events
      in late juvenile astrocytes were not affected by spontaneously occurring sharp
      waves that trigger synchronized neuronal spikes, implying the independence of
      astrocyte calcium signals from neuronal synchronization. These results
      demonstrate that astrocytes undergo dynamic changes in their activity patterns
      during juvenile development. 

PMID- 27041235
TI  - A dietary polyphenol resveratrol acts to provide neuroprotection in recurrent
      stroke models by regulating AMPK and SIRT1 signaling, thereby reducing energy
      requirements during ischemia.
AB  - The above article from European Journal of Neuroscience, published online on 5
      March 2013 in Wiley Online Library
      (http://onlinelibrary.wiley.com/doi/10.1111/ejn.12162/full), has been retracted
      by agreement between the Editors-in-Chief, Paul Bolam and John Foxe, the authors
      and John Wiley & Sons Ltd. The retraction has been agreed as Dr Phillip Barber
      has informed the publisher that he had seen neither the original data nor any
      version of the manuscript, and had not been involved in the work reported. A
      subsequent Institutional investigation found evidence of misconduct on the part
      of the submitting author. Reference Wang, L.-M., Wang, Y.-J., Cui, M., Luo, W.
      J., Wang, X.-J., Barber, P.A. & Chen, Z.-Y. (2013) A dietary polyphenol
      resveratrol acts to provide neuroprotection in recurrent stroke models by
      regulating AMPK and SIRT1 signaling, thereby reducing energy requirements during
      ischemia.

PMID- 27041236
TI  - No more pain upon Gq-protein-coupled receptor activation: role of
      endocannabinoids.
AB  - The above article from European Journal of Neuroscience, published online on 4
      February 2014 in Wiley Online Library
      (http://onlinelibrary.wiley.com/doi/10.1111/ejn.12475/full), has been retracted
      by agreement between the Editors-in-Chief, Paul Bolam and John Foxe, the authors
      and John Wiley & Sons Ltd. The retraction has been agreed as the above article
      has been found to overlap substantially with the article 'Chiou, L.-C., Hu, S. S.
      J., and Ho, Y.-C. (2013), Targeting the cannabinoid system for pain relief? Acta
      Anaesthesiologica Taiwanica, Volume 51, Issue 4: 161 - 170. doi:
      10.1016/j.aat.2013.10.004', which was submitted after the European Journal of
      Neuroscience article but was published first. Reference Hu, S.S.-J., Ho, Y.-C. &
      Chiou, L.-C. (2014) No more pain upon Gq-protein-coupled receptor activation:
      role of endocannabinoids.

PMID- 27041237
TI  - Using network projections to explore co-incidence and context in large clinical
      datasets: Application to homelessness among U.S. Veterans.
AB  - INTRODUCTION: Network projections of data can provide an efficient format for
      data exploration of co-incidence in large clinical datasets. We present and
      explore the utility of a network projection approach to finding patterns in
      health care data that could be exploited to prevent homelessness among U.S.
      Veterans. METHOD: We divided Veteran ICD-9-CM (ICD9) data into two time periods
      (0-59 and 60-364days prior to the first evidence of homelessness) and then used
      Pajek social network analysis software to visualize these data as three different
      networks. A multi-relational network simultaneously displayed the magnitude of
      ties between the most frequent ICD9 pairings. A new association network
      visualized ICD9 pairings that greatly increased or decreased. A signed,
      subtraction network visualized the presence, absence, and magnitude difference
      between ICD9 associations by time period. RESULT: A cohort of 9468 U.S. Veterans
      was identified as having administrative evidence of homelessness and visits in
      both time periods. They were seen in 222,599 outpatient visits that generated
      484,339 ICD9 codes (average of 11.4 (range 1-23) visits and 2.2 (range 1-60) ICD9
      codes per visit). Using the three network projection methods, we were able to
      show distinct differences in the pattern of co-morbidities in the two time
      periods. In the more distant time period preceding homelessness, the network was
      dominated by routine health maintenance visits and physical ailment diagnoses. In
      the 59days immediately prior to the homelessness identification, alcohol related
      diagnoses along with economic circumstances such as unemployment, legal
      circumstances, along with housing instability were noted. CONCLUSION: Network
      visualizations of large clinical datasets traditionally treated as tabular and
      difficult to manipulate reveal rich, previously hidden connections between data
      variables related to homelessness. A key feature is the ability to visualize
      changes in variables with temporality and in proximity to the event of interest.
      These visualizations lend support to cognitive tasks such as exploration of large
      clinical datasets as a prelude to hypothesis generation.

PMID- 27041238
TI  - Staged Repair of an Aortopulmonary Fistula From a Large Ascending Aortic
      Pseudoaneurysm: The Role of Transesophageal Echocardiography.

PMID- 27041239
TI  - Proteome scale census of major facilitator superfamily transporters in
      Trichoderma reesei using protein sequence and structure based classification
      enhanced ranking.
AB  - Trichoderma spp. have been acknowledged as potent bio-control agents against
      microbial pathogens and also as plant growth promoters. Various secondary
      metabolites are attributed for these beneficial activities. Major facilitator
      superfamily (MFS) includes the large proportion of efflux-pumps which are linked
      with membrane transport of these secondary metabolites. We have carried out a
      proteome-wide identification of MFS transporters using protein sequence and
      structure based hierarchical method in Trichoderma reesei. 448 proteins out of
      9115 were detected to carry transmembrane helices. MFS specific intragenic gene
      duplication and its context with transport function have been presented. Finally,
      using homology based techniques, domains and motifs of MFS families have been
      identified and utilized to classify them. From query dataset of 448 transmembrane
      proteins, 148 proteins are identified as potential MFS transporters. Sugar
      porter, drug: H(+) antiporter-1, monocarboxylate porter and anion: cation
      symporter emerged as major MFS families with 51, 35, 17 and 11 members
      respectively. Representative protein tertiary structures of these families are
      homology modeled for structure-function analysis. This study may help to
      understand the molecular basis of secretion and transport of agriculturally
      valuable secondary metabolites produced by these bio-control fungal agents which
      may be exploited in future for enhancing its biotechnological applications in eco
      friendly sustainable development. 

PMID- 27041240
TI  - SRPK2 promotes the growth and migration of the colon cancer cells.
AB  - Colon cancer is one of the major causes of cancer-related death in the world.
      Understanding the molecular mechanism underlying this malignancy will facilitate
      the diagnosis and treatment. Serine-arginine protein kinase 2 (SRPK2) has been
      reported to be upregulated in several cancer types. However, its expression and
      functions in colon cancer remains unknown. In this study, it was found that the
      expression of SRPK2 was up-regulated in the clinical colon cancer samples.
      Overexpression of SRPK2 promoted the growth and migration of colon cancer cells,
      while knocking down the expression of SRPK2 inhibited the growth, migration and
      tumorigenecity of colon cancer cells. Molecular mechanism studies revealed that
      SRPK2 activated ERK signaling in colon cancer cells. Taken together, our study
      demonstrated the tumor promoting roles of SRPK2 in colon cancer cells and SRPK2
      might be a promising therapeutic target for colon cancer. 

PMID- 27041241
TI  - Multiple functions of the histone chaperone Jun dimerization protein 2.
AB  - The Jun dimerization protein 2 (JDP2) is part of the family of stress-responsible
      transcription factors such as the activation protein-1, and binds the 12-O
      tetradecanoylphorbol-13-acetateresponse element and the cAMP response element. It
      also plays a role as a histone chaperone and participates in diverse processes,
      such as cell-cycle arrest, cell differentiation, apoptosis, senescence, and
      metastatic spread, and functions as an oncogene and anti-oncogene, and as a
      cellular reprogramming factor. However, the molecular mechanisms underlying these
      multiple functions of JDP2 have not been clarified. This review summarizes the
      structure and function of JDP2, highlighting the specific role of JDP2 in
      cellular-stress regulation and prevention. 

PMID- 27041242
TI  - Validation of RT-qPCR reference genes and determination of Robo4 expression
      levels in human retinal endothelial cells under hypoxia and/or hyperglycemia.
AB  - Real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR)
      has become the most common technique to investigate mRNA expression levels of
      target genes. In order to obtain accurate results, stable reference genes need to
      be selected for normalization in an experimental study. Human retinal endothelial
      cells (HREC) cultured in a hypoxic and hyperglycemic environment is a potential
      cell model to study diabetic retinopathy (DR), but the proper reference genes for
      RNA analysis have not yet been determined. In the present study, we evaluated the
      expression levels of 14 candidate housekeeping genes and selected the most
      suitable reference genes for RT-qPCR for HREC under hypoxic and/or hyperglycemic
      conditions. The results of the analyses using GeNorm, NormFinder, and BestKeeper
      software showed that a combination of TBP, PUM1, and ALAS1 was most suitable for
      this research. Based on these results, mRNA expression levels of Roundabout4
      (Robo4) in HREC were determined. The RT-qPCR analysis showed that there was a
      significant increase in Robo4 expression under hyperglycemic conditions, while
      there was a decrease in expression under hypoxic and combined hypoxic and
      hyperglycemic conditions, suggesting that Robo4 might play different roles in
      various stages of DR.

PMID- 27041243
TI  - Highly stable nanofluid based on polyhedral oligomeric silsesquioxane-decorated
      graphene oxide nanosheets and its enhanced electro-responsive behavior.
AB  - Graphene oxide (GO) shows potential as an anisotropic nanofiller or a dispersed
      phase of electro-responsive electrorheological (ER) nanofluid due to its small
      size and high aspect ratio. But it is difficult to disperse GO in non-polar oil
      due to the hydrophilic nature of GO and thus the resulting fluid is often subject
      to dispersion instability and low ER effect. These disadvantages largely limit
      the real application of GO-based ER nanofluid. In this paper, we develop the
      polyhedral oligomeric silsesquioxane (POSS)-decorated GO (POSS-GO) nanosheets and
      demonstrate that decorating with POSS overcomes the dispersion instability of GO
      in silicone oil and enhances the ER effect. The morphology and structure of
      samples are characterized by atomic force microscopy, Fourier transform infrared
      spectroscopy, thermogravimetric analysis, and x-ray photoelectronic spectroscopy.
      The results show that the POSS-GO nanosheets are ultrathin with ~3 nm thickness
      and have good compatibility with silicone oil and, as a result, the nanofluid of
      POSS-GO nanosheets in silicone oil shows high dispersion stability. After
      standing for one year at room temperature, no sedimentation occurs. Under an
      external electric field, the ER efficiency of the POSS-GO nanofluid is ten times
      as high as that of the pure GO fluid. This enhanced electro-responsive behavior
      is related to the fact that decorating with POSS partly reduces the GO and
      compresses the dielectrophoretic effect of the negatively charged pure GO fluid. 

PMID- 27041244
TI  - Plasma VEGF and IL-8 Levels in Patients with Mixed Dyslipidaemia. Effect of
      Rosuvastatin Monotherapy or its Combination at a Lower Dose with Omega-3 Fatty
      Acids: A Pilot Study.
AB  - OBJECTIVES: Hypercholesterolaemia is associated with increased plasma levels of
      vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). We studied
      the effect of rosuvastatin monotherapy or its combination at a lower dose with
      omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in the VEGF and IL-8 plasma
      levels in patients with mixed dyslipidaemia. METHODS: Fifty patients with mixed
      dyslipidaemia were recruited. Fifty-five normolipidaemic, apparently healthy,
      ageand sex- matched subjects acted as controls. Patients were randomized to 40
      mg/day rosuvastatin (R group, n=26) or 10 mg/day rosuvastatin plus 2 g/day of
      omega-3 PUFAs (R+O group, n=24). The levels of VEGF and IL-8 in plasma, were
      assessed at baseline and 3 months post-treatment. RESULTS: At baseline, both
      plasma VEGF and IL-8 levels were significantly higher in the R and R+O groups
      compared with controls (p<0.04, p<0.03 and p<0.02, p<0.03, respectively). Post
      treatment levels of VEGF were decreased in the R group while a significant
      increase was observed in the R+O group, compared with baseline levels (p<0.02 and
      p<0.03, respectively). Post-treatment IL-8 levels were decreased in both R and
      R+O groups (p<0.03 and p<0.04, respectively). CONCLUSIONS: We show for the first
      time that either rosuvastatin monotherapy or its combination at a lower dose with
      omega-3 PUFAs reduces IL-8 levels in mixed dyslipidaemic patients. High-dose
      rosuvastatin monotherapy reduces VEGF values, whereas a significant increase is
      observed in patients receiving lower dose rosuvastatin with omega-3 PUFAs. The
      clinical significance of the above findings regarding cardiovascular risk remains
      to be established.

PMID- 27041245
TI  - HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -E, -F and -G genotyping of 130 individuals
      from Terceira Island, Azores, Portugal.
AB  - One hundred and thirty unrelated Azorean individuals were randomly selected to
      study the frequencies of high-resolution HLA alleles and haplotypes in the
      Azorean (Terceira) population. HLA-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 high
      resolution genotyping was performed by polymerase chain reaction using commercial
      kits. HLA-E, -F and -G alleles, were genotyped by sequence-based typing. All loci
      were in HWE, showing no locus-level deviations. The genotype data is available in
      the Allele Frequencies Net Database under the population name "Azores Terceira
      Island" and the identifier (AFND112579). 

PMID- 27041246
TI  - Severe hypersplenism associated to hemophagocytic and lymphoproliferative
      syndrome secondary to Epstein-Barr virus infection. A report of two cases.

PMID- 27041247
TI  - Augmenter of liver regeneration attenuates acute rejection after rat liver
      transplantation.
AB  - BACKGROUND: The role of augmenter of liver regeneration (ALR) on liver
      transplantation immune regulation remains unknown. METHODS: Male Lewis and Brown
      Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver
      transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100
      MUg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at
      indicated times for assessment of cytokines production, T-cell (TC) activation
      and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess
      cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of
      (3)H-thymidine TCs. RESULTS: (1) Treatment with ALR significantly decreased
      interleukin-2 and interferon-gamma expression, promoted TC apoptosis, and
      prolonged the survival of allografts; (2) KCs in ALR group and isograft group
      that had significantly increased interleukin-10 and decreased tumor necrosis
      factor-alpha expression were able to inhibit TC proliferation and induce their
      apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly
      inhibited TC proliferation and activation and induced TC apoptosis. CONCLUSIONS:
      ALR could inhibit TC proliferation and function both in vivo and in vitro and
      attenuate acute rejection after liver transplantation.

PMID- 27041248
TI  - 2,3-Butanedione monoxime facilitates successful resuscitation in a dose-dependent
      fashion in a pig model of cardiac arrest.
AB  - PURPOSE: Ischemic contracture compromises the hemodynamic effectiveness of
      cardiopulmonary resuscitation (CPR) and resuscitability from cardiac arrest. In a
      pig model of cardiac arrest, 2,3-butanedione monoxime (BDM) attenuated ischemic
      contracture. We investigated the effects of different doses of BDM to determine
      whether increasing the dose of BDM could improve the hemodynamic effectiveness of
      CPR further, thus ultimately improving resuscitability. METHODS: After 16minutes
      of untreated ventricular fibrillation and 8minutes of basic life support, 36 pigs
      were divided randomly into 3 groups that received 50mg/kg (low-dose group) of
      BDM, 100mg/kg (high-dose group) of BDM, or an equivalent volume of saline
      (control group) during advanced cardiovascular life support. RESULTS: During
      advanced cardiovascular life support, the control group showed an increase in
      left ventricular (LV) wall thickness and a decrease in LV chamber area. In
      contrast, the BDM-treated groups showed a decrease in the LV wall thickness and
      an increase in the LV chamber area in a dose-dependent fashion. Mixed-model
      analyses of the LV wall thickness and LV chamber area revealed significant group
      effects and group-time interactions. Central venous oxygen saturation at 3minutes
      after the drug administration was 21.6% (18.4-31.9), 39.2% (28.8-53.7), and 54.0%
      (47.5-69.4) in the control, low-dose, and high-dose groups, respectively
      (P<.001). Sustained restoration of spontaneous circulation was attained in 7
      (58.3%), 10 (83.3%), and 12 animals (100%) in the control, low-dose, and high
      dose groups, respectively (P=.046). CONCLUSION: 2,3-Butanedione monoxime
      administered during CPR attenuated ischemic contracture and improved the
      resuscitability in a dose-dependent fashion.

PMID- 27041249
TI  - Changing epidemiology and management of infectious diseases in US EDs.
AB  - BACKGROUND: The rise of antibiotic-resistant pathogens is believed to have
      influenced the emergency department (ED) epidemiology and management of
      infectious diseases (IDs) since 2000. METHODS: Data from the National Hospital
      Ambulatory Medical Care Survey from 2000 to 2010 were used to examine temporal
      trends in the incidence of IDs presenting to EDs. Outcome measures included
      national visit rates, visit proportions, and antimicrobial prescriptions for all
      ID primary diagnoses, as well as for specific organ systems of interest
      (respiratory tract, skin/soft tissue, and urinary tract). RESULTS: An ID-related
      primary diagnosis was given in 18.3% (95% confidence interval, 17.9%-18.8%) of
      all ED visits during the study period. The hospitalization rate for these
      conditions is 7.8% (95% confidence interval, 7.3%-8.3%). The share of macrolide
      prescriptions for upper respiratory tract infections and lower respiratory tract
      infections increased by 34% and 46%, respectively, and that of quinolone
      prescription for lower respiratory tract infections doubled from 9% to 18.4%
      during the study period. Management of skin and soft tissue infections shifted
      from predominant use of cephalosporins to sulfonamides. For UTIs, quinolones were
      most commonly prescribed, with an increasing use of third-generation
      cephalosporins. Antibiotics were more frequently prescribed to patients who are
      white compared with (white: 60%, black: 57%, other races: 52%, P < .05).
      CONCLUSION: The changing epidemiology of IDs diagnosed in US EDs reflects
      national trends in emerging pathogens and drug resistance. Broad-spectrum
      antibiotics are being prescribed at increasing rates. There are significant
      demographic disparities in nationwide antibiotic prescription practices.

PMID- 27041250
TI  - [Not Available].

PMID- 27041251
TI  - Is a negative urine drug screen truly negative?

PMID- 27041252
TI  - Wound dehiscence after general anesthesia in a child.

PMID- 27041253
TI  - A short view of chronic graft-vs-host disease.

PMID- 27041254
TI  - A patient with Churg-Strauss syndrome complicated with pulmonary hemoptysis.

PMID- 27041255
TI  - Lead through needle technique for placing spinal cord stimulator leads: a novel
      alternative to the loss of resistance technique.

PMID- 27041256
TI  - Ultrasound-assisted transversus abdominis plane block vs wound infiltration in
      pediatric patient with inguinal hernia: randomized controlled trial.
AB  - STUDY OBJECTIVE: To compare the analgesic efficacy of ultrasound-assisted
      transversus abdominis plane (TAP) block and wound infiltration during the first
      postoperative 24hours. DESIGN: A prospective, observer-blinded, randomized, and
      controlled study SETTING: Operating room of a university hospital. PATIENTS:
      Forty patients received a TAP block (TAP group) and 40 patients received wound
      infiltration (INF group) at the end of the surgery. INTERVENTIONS: Patients were
      randomized to receive a TAP block or wound infiltration. Postoperative analgesics
      were administered on request and selected based on pain severity. MEASUREMENTS:
      Pain scores, analgesic drug requirement, and side effects were observed for
      24hours. MAIN RESULTS: Postoperative pain scores were lower in TAP group compared
      to INF group (P<.001). Analgesic consumption was significantly higher at the 5th
      minute and 1st, 6th, and 12th hours in the INF group (P<.001). The frequency of
      additional analgesic use in home and the total analgesic used during the
      postoperative 24hours were significantly higher in INF group (P<.001). Side
      effects were lower in the TAP group. Parent's satisfaction scores were higher in
      TAP group. CONCLUSION: Transversus abdominis plane block is effective method with
      convenient technique, drug dosage, and volume in pediatric patients undergoing
      inguinal hernia surgery.

PMID- 27041257
TI  - A randomized trial examining preoperative sedative medication and postoperative
      sleep in children.
AB  - STUDY OBJECTIVE: Midazolam has been found to have beneficial effects on anxiety
      in children in the preoperative setting. Prior studies have examined various
      postoperative behaviors of children, but little research has examined the effects
      of preoperative use of midazolam with postoperative sleep. The purpose of this
      investigation was to compare postoperative sleep in children as a function of
      preoperative sedative medication use. DESIGN: This study was a 2-group randomized
      controlled trial. SETTING: Participants were recruited from Yale-New Haven
      Children's Hospital. PATIENTS: Participants included a convenience sample of 70
      children between the ages of 3 to 12 years undergoing ambulatory tonsillectomy
      and adenoidectomy. INTERVENTIONS: Children were randomly assigned to 1 of 2
      groups: a control group who received preoperative acetaminophen only (n = 32) and
      an experimental group who received both acetaminophen and midazolam
      preoperatively (n = 38). MEASUREMENTS: Parents completed measures of
      postoperative behavioral recovery and a subset of children wore actigraphs to
      examine objective sleep data. MAIN RESULTS: Children who received midazolam
      experienced similar sleep changes compared to children in the control group. The
      actigraph data revealed that children who received midazolam were awake
      significantly less during the night compared to the control group (P= .01).
      CONCLUSION: Children who received midazolam before surgery had similar
      postoperative sleep changes compared to children who did not receive midazolam.
      Further understanding of the postoperative behavioral effects of midazolam on
      children will help guide healthcare providers in their practice.

PMID- 27041258
TI  - Postoperative conversion disorder.
AB  - Conversion disorder is a psychiatric disorder in which psychological stress
      causes neurologic deficits. A 28-year-old female surgical patient had uneventful
      general anesthesia and emergence but developed conversion disorder 1 hour
      postoperatively. She reported difficulty speaking, right-hand numbness and
      weakness, and right-leg paralysis. Neurologic examination and imaging revealed no
      neuronal damage, herniation, hemorrhage, or stroke. The patient mentioned failing
      examinations the day before surgery and discontinuing her prescribed
      antidepressant medication, leading us to diagnose conversion disorder, with
      eventual confirmation by neuroimaging and follow-up examinations. 

PMID- 27041259
TI  - Preventable drug waste among anesthesia providers: opportunities for efficiency.
AB  - BACKGROUND: Health care service bundling experiments at the state and regional
      levels have showed reduced costs by providing a single lump-sum reimbursement for
      anesthesia services, surgery, and postoperative care. Potential for cost savings
      related to the provision of anesthesia care has the potential to significantly
      impact sustainability. This study defines and quantifies routine and preventable
      anesthetic drug waste and the patient, procedure, and anesthesia provider
      characteristics associated with increased waste. METHODS: Over a 12-month period,
      the type and quantity of clean drugs prepared by the anesthesia team for the
      first case of the day were recorded. The amount of each drug administered was
      obtained from the computerized anesthesia record, and data were analyzed to
      determine the incidence and cost of routine and preventable drug waste. The
      monthly and yearly cost of preventable waste, including the cost of pharmacy tech
      labor and materials where applicable, was estimated based on surgical case volume
      at the study institution. All analyses were performed using SAS software v9.2.
      RESULTS: Anesthetic drugs prepared for 543 separate surgical cases were observed.
      Less than 20% of cases generated routine waste. Preventable waste was generated
      most frequently for ephedrine (59.5% of cases), succinylcholine (33.7%), and
      lidocaine (25.1%), and least frequently for ondansetron (1.3%), phenylephrine
      (2.6%), and dexamethasone (2.8%). The estimated yearly cost of preventable
      anesthetic drug waste was $185,250. CONCLUSIONS: Significant potential savings
      with little impact on clinically significant availability may be achieved through
      the use of prefilled syringes for some commonly used anesthetic drugs. An
      intelligently implemented switch to prefilled syringes for select drugs is a
      potential cost saving measure, but savings might be diminished by disposal of
      prefilled syringes when they expire, hidden costs in the hospital pharmacy, and
      inability to supply some medications in prefilled syringes due to stability or
      manufacturing issues.

PMID- 27041260
TI  - The risk factors for postoperative pulmonary complications after head and neck
      cancer surgery.

PMID- 27041261
TI  - Classic transcrural celiac plexus block simulated on 100 computed tomography
      images.
AB  - STUDY OBJECTIVE: To evaluate intra-abdominal needle trajectories of the classic
      transcrural celiac plexus block (tCPB) with a simulation technique. DESIGN:
      Classic tCPB technique cited from 10 latest authoritative textbooks were
      simulated on abdominal computed tomography images retrospectively. SETTING:
      University-affiliated community hospital. MEASUREMENTS: One hundred axial
      computed tomography images across the celiac trunk were retrieved. Three lines
      simulating classic tCPB were executed on each image. The organs traversed by each
      line were noted and analyzed. The frequencies of organ traverse were compared
      with the incidences described in the literature. MAIN RESULTS: All 3 lines
      traversed various organs with different frequencies. The right side line
      frequently traversed the right kidney (36%). The left side line always traversed
      the aorta (100%). The modified line on the right side frequently traversed the
      inferior vena cava (32%). The highest kidney traverse percentage on both sides
      and the highest aorta traverse percentage on the right side were observed in
      pancreatic cancer patients. CONCLUSIONS: Despite uncommon clinical complications,
      classic tCPB needle placement frequently traversed through several key organs in
      this simulation series. Organ penetrations could be avoided by needle trajectory
      adjustment.

PMID- 27041262
TI  - Adopting the American anesthesia oral examination in China: value and roadblocks.
AB  - The quality and standardized training and certification of young physicians is
      key to the quality of health care in the future. In contrast to the American
      system, there is no nationwide and standardized oral examination in the training
      and certification process for anesthesiologists in China. The adoptability of the
      American anesthesia oral examination in China, as well as potential roadblocks,
      has not been specifically discussed. In this commentary, we share our experience
      of introducing the American oral examination to an audience of Chinese
      anesthesiologists and propose a pragmatic approach for adopting the anesthesia
      oral examination in China. This initiative has the potential to reform the
      current anesthesia training and certification process and improve the quality of
      anesthetic care in China. 

PMID- 27041263
TI  - Hemodynamics of mesenteric traction syndrome measured by FloTrac sensor.
AB  - BACKGROUND: Mesenteric traction syndrome (MTS) develops in the early phase of
      laparotomy, which is triggered by pulling of the mesentery. We attempted to
      analyze the circulatory dynamics of MTS by using the FloTrac sensor. METHODS:
      Prospective randomized control study, the MTS trial, was conducted with or
      without prophylactic administration of flurbiprofen axetil in order to control
      MTS development in 57 elective open colorectal surgeries. None of the
      Flurbipurofen group patients (n = 23) develop MTS and were allocated to the non
      MTS group. Among the non-flurbiprofen group, 28 patients (82%) developed MTS and
      were categorized into the MTS group. For these patients, in addition to blood
      pressure, stroke volume variation (SVV) and systemic vascular resistance index
      (SVRI) were measured by FloTrac sensor. RESULTS: The lowest blood pressure was
      noted within 30 minutes from the beginning of the intra-abdominal examination; in
      the non-MTS group, the mean blood pressure decreased by 16.7%, and in the MTS
      group, it decreased by 34.2% (P < .01). SVV of the 28 MTS patients was as
      follows: <9% in 10 patients (35.7%), >9% and <13% in 8 patients (28.6%), and >13%
      in 10 patients (35.7%). SVRI rose in the non-MTS group by 5.1%, whereas it fell
      in the MTS group by 15.1% (P < .01), indicating the close relationship between
      MTS and SVRI. CONCLUSIONS: The SVV results indicate that fluid loading is not
      that optimal treatment against hypotension of MTS and that it is also important
      to consider the use of a vasoconstrictor. FloTrac is therefore useful for making
      an appropriate decision on the treatment strategy for MTS.

PMID- 27041264
TI  - The history of the nurse anesthesia profession.
AB  - Despite the fact that anesthesia was discovered in the United States, we believe
      that both physicians and nurses are largely unaware of many aspects of the
      development of the nurse anesthetist profession. A shortage of suitable
      anesthetists and the reluctance of physicians to provide anesthetics in the
      second half of the 19th century encouraged nurses to take on this role. We trace
      the origins of the nurse anesthetist profession and provide biographical
      information about its pioneers, including Catherine Lawrence, Sister Mary Bernard
      Sheridan, Alice Magaw, Agatha Cobourg Hodgins, and Helen Lamb. We comment on the
      role of the nuns and the effect of the support and encouragement of senior
      surgeons on the development of the specialty. We note the major effect of World
      Wars I and II on the training and recruitment of nurse anesthetists. We provide
      information on difficulties faced by nurse anesthetists and how these were
      overcome. Next, we examine how members of the profession organized, developed
      training programs, and formalized credentialing and licensing procedures. We
      conclude by examining the current state of nurse anesthesia practice in the
      United States. 

PMID- 27041265
TI  - Evaluation of gum-elastic bougie with direct and indirect laryngoscope for infant
      difficult airway management: a Pierre Robin simulation model.

PMID- 27041266
TI  - Evaluation of pH in the removed i-gel after general anesthesia: a prospective
      observational study.

PMID- 27041267
TI  - Increased airway pressure due to superior mediastinal hematoma during
      endovascular coiling by transcarotid approach.
AB  - An elderly woman with subarachanoid hemorrhage presented to our interventional
      neuroradiology suite for coil embolization of multiple intracranial aneurysms.
      The patient had difficult vascular access for the passage of microcatheter;
      hence, the embolization procedure was carried out with direct puncture of the
      left common carotid artery. During the procedure, the patient developed
      thromboembolism which was treated by administration of an antiplatelet agent,
      abciximab. At the end of procedure, she developed airway compromise due to
      extension of a local neck hematoma into the superior mediastinum. The management
      issues in such a scenario have been discussed. 

PMID- 27041268
TI  - Monitoring of oropharyngeal leak pressures using cuff manometer/cuff inflator
      device.

PMID- 27041269
TI  - Is the Ambu aScope 3 Slim single-use fiberscope equally efficient compared with a
      conventional bronchoscope for management of the difficult airway?
AB  - STUDY OBJECTIVE: The study objective was to evaluate whether the single-use
      fiberoptic bronchoscope (FOB), Ambu aScope 3 Slim, was equally efficient compared
      with the conventional reusable FOB, Olympus LF-GP, for nasal fiberoptic
      intubation in a manikin. DESIGN: A randomized crossed-over study. SETTING: The
      postanesthesia care unit of Tokyo Women's Medical University Hospital. SUBJECTS:
      Twenty anesthesiologists who have experienced >50 one-lung ventilation thoracic
      surgery procedures were invited to participate in this study. INTERVENTIONS: A
      6.5-mm internal diameter cuffed endotracheal tube (ET) was inserted into the
      manikin under Ambu aScope 3 Slim (group A) or Olympus LF-GP (group C) guidance.
      MEASUREMENTS: The following time parameters from the beginning of FOB insertion
      through a nostril were compared between groups: until vocal cord visualization
      (T1); visualization of the carina (T2); and proper ET placement, as confirmed by
      the distance of the ET tip to carina (T3). MAIN RESULTS: Mean (SD) T1 in group A
      and group C were 20 seconds (17 seconds) and 14 seconds (12 seconds),
      respectively (P= .1050). Mean (SD) T2 in group A and group C were 40 seconds (29
      seconds) and 25 seconds (15 seconds), respectively (P= .0287). Mean (SD) T3 in
      group A and group C were 70 seconds (33 seconds) and 50 seconds (22 seconds),
      respectively (P= .0098). One case in group A had failed intubation CONCLUSIONS:
      The Ambu aScope 3 Slim required more time to intubate than the conventional
      reusable FOB. It requires more rigidity, similar to the conventional FOB for
      management of the difficult airway.

PMID- 27041270
TI  - Clinical efficacy of modified thoracolumbar interfascial plane block.

PMID- 27041271
TI  - The SorbaView SHIELD is a useful product for fixation of continuous catheter
      performing in femoral nerve block.

PMID- 27041272
TI  - Subtenon block combined with general anesthesia for vitreoretinal surgery
      improves postoperative analgesia in adult: a randomized controlled trial.
AB  - STUDY OBJECTIVE: To evaluate the effects of subtenon block (SB) as an adjunct to
      general anesthesia on intraoperative oculocardiac reflex (OCR), postoperative
      pain, and postoperative nausea and vomiting (PONV) for vitreoretinal surgery.
      DESIGN: Prospective, randomized, double-blinded clinical trial. SETTING:
      Operating room, postanesthesia care unit, and ward at a university-affiliated
      hospital. PATIENTS: Eighty patients aged 40 to 65 years of American Society of
      Anesthesiologists I to II requesting general anesthesia for vitreoretinal
      surgery. Intervention and Measurements Patients were randomly assigned to 1 of 2
      groups receiving either SB with mixture of 4 mL of 2% lidocaine and 0.5%
      bupivacaine (50:50) in group SB or subtenon injection of saline in group C after
      induction of anesthesia and before surgery in a double-blind manner. The time to
      first postoperative analgesic dose, incidence of intraoperative OCR,
      postoperative pain scores, perioperative analgesic requirements, number of
      patients requiring rescue analgesics during the 24-hour study period, incidence
      of PONV, and possible complications were recorded. RESULTS: Time to first
      postoperative analgesia was significantly longer in group SB (P= .002). Pain
      scores at the first 6 hours postoperatively were significantly lower in group SB
      (P= .002). Intraoperative and postoperative analgesic requirements were
      significantly reduced in group SB (P= .015). The incidence of OCR and PONV also
      significantly decreased in this group (P= .001 and P= .011, respectively).
      CONCLUSION: Use of SB combined with general anesthesia in patients undergoing
      vitreoretinal surgery reduces postoperative analgesic requirements and
      complications such as intraoperative OCR and PONV.

PMID- 27041273
TI  - Cotton Leaf Curl Multan Betasatellite DNA as a Tool to Deliver and Express the
      Human B-Cell Lymphoma 2 (Bcl-2) Gene in Plants.
AB  - The betasatellite DNA associated with Cotton leaf curl Multan virus (CLCuMB)
      contains a single complementary-sense ORF, betaC1, which is a pathogenicity
      determinant. CLCuMB was able to replicate in plants in the presence of diverse
      helper geminiviruses, including Tomato leaf curl virus-Australia (TLCV-Au),
      Iranian isolate of Tomato yellow leaf curl virus (TYLCV-[Ab]), and Beet curly top
      virus (BCTV-Svr), and can be used as a plant gene delivery vector. To test the
      hypothesis that CLCuMB has the potential to act as an animal gene delivery
      vector, a specific insertion construct was produced by the introduction of a
      human B-cell lymphoma 2 (Bcl-2) cDNA into a mutant DNA of CLCuMB in which the
      betaC1 was deleted (beta?C1). The recombinant betaDeltaC1-Bcl-2 construct was
      successfully replicated in tomato and tobacco plants in the presence of TLCV-Au,
      BCTV-Svr and TYLCV-[Ab]. Real-time PCR and Western blot analyses of plants
      containing the replicative forms of recombinant betaDeltaC1-Bcl-2 DNA showed that
      Bcl-2 gene was expressed in an acceptable level in these plants, indicating that
      beta?C1 can be used as a tool to deliver and express animal genes in plants. This
      CLCuMB-based system, having its own promoter activity, offers the possibility of
      production of animal recombinant proteins in plants. 

PMID- 27041274
TI  - Colorimetric Glucose Assay Based on Magnetic Particles Having Pseudo-peroxidase
      Activity and Immobilized Glucose Oxidase.
AB  - Magnetic particles (MPs) are currently used as a suitable alternative for
      peroxidase in the construction of novel biosensors, analytic and diagnostic
      methods. Their better chemical and thermal stabilities predestine them as
      appropriate pseudo-enzymatic catalysts. In this point of view, our research was
      focused on preparation of simply and fast method for immobilization of glucose
      oxidase onto surface of MPs with peroxidase-like activity. Spectrophotometric
      method (wavelength 450 nm) optimized for glucose determination using modified MPs
      has been successfully developed. Concentration curve for optimization of method
      was assayed, and Michaelis-Menten constant (K m) calculated, maximum reaction
      rate (V max), limit of detection, and correlation coefficient were determined to
      be 0.13 mmol/l (2.34 mg/dl), 1.79 pkat, 3.74 umol/l (0.067 mg/dl), and 0.996,
      respectively. Interferences of other sugars such as sucrose, sorbitol,
      deoxyribose, maltose, and fructose were determined as well as effect of
      substances presenting in plasma (ascorbic acid, reduced glutathione, trolox, and
      urea). Results in comparison with positive and negative controls showed no
      interferences of the other sugars and no influence of plasma substances to
      measuring of glucose. The constructed method showed corresponding results with
      linear dependence and a correlation coefficient of 0.997. Possibility of repeated
      use of modified MPs was successfully proved.

PMID- 27041275
TI  - Erratum to: Metaphyseal osteomyelitis in children: how often does MRI-documented
      joint effusion or epiphyseal extension of edema indicate coexisting septic
      arthritis?

PMID- 27041276
TI  - Safety of gadobutrol in more than 1,000 pediatric patients: subanalysis of the
      GARDIAN study, a global multicenter prospective non-interventional study.
AB  - BACKGROUND: Gadobutrol is a gadolinium-based contrast agent, uniquely formulated
      at 1.0 mmol/ml. Although there is extensive safety evidence on the use of
      gadobutrol in adults, few studies have addressed the safety and tolerability of
      gadobutrol in pediatric patients. OBJECTIVE: This subanalysis of data from the
      GARDIAN study evaluated the safety and use of gadobutrol in pediatric patients
      (age <18 years). MATERIALS AND METHODS: The GARDIAN study was a large phase IV
      non-interventional prospective multicenter post-authorization safety study
      performed in Europe, Asia, North America and Africa. A total of 23,708 patients
      were included who were scheduled to undergo cranial or spinal MRI, liver or
      kidney MRI, or MR angiography with gadobutrol enhancement. The primary study
      endpoint was the overall incidence of adverse drug reactions (ADRs) and serious
      adverse events (SAEs) following gadobutrol administration. RESULTS: The GARDIAN
      study included 1,142 children (age <18 years) who received gadobutrol at a mean
      dose of 0.13 (range 0.04-0.50) mmol/kg body weight. Gadobutrol was well tolerated
      in these children, with low rates of ADRs (0.5%) and no SAEs, consistent with
      results in adults enrolled in the GARDIAN study. Rates of adverse events and ADRs
      were unrelated to pediatric age or gadobutrol weight-adjusted dose. There were no
      symptoms suggestive of nephrogenic systemic fibrosis. Investigators rated the
      contrast quality of gadobutrol-enhanced images as good or excellent in 97.8% of
      pediatric patients, similar to the main study population. CONCLUSION: Gadobutrol
      is very well tolerated and provides excellent contrast quality at the recommended
      weight-adjusted dose in children (age <18 years), similar to the profile in
      adults.

PMID- 27041277
TI  - CT-defined phenotype of pulmonary artery stenoses in Alagille syndrome.
AB  - BACKGROUND: Alagille syndrome is a rare disorder commonly associated with
      pulmonary artery stenosis. Studies exist discussing the cardiovascular sequela
      but no consistent phenotype, or pattern of pulmonary artery stenosis, has been
      described. OBJECTIVE: The objective of this study was to characterize the
      distribution and severity of pulmonary artery stenosis in patients with Alagille
      syndrome based on computed tomography angiography. MATERIALS AND METHODS: A
      retrospective chart review identified patients with Alagille syndrome who had
      undergone CT angiography. Pulmonary trunk (MPA), left main pulmonary artery (LPA)
      and right main pulmonary artery (RPA) diameters in Alagille patients were
      compared with those from matched control subjects. Stenoses at lobar and
      segmental pulmonary arteries were categorized as: Grade 1 (<33% stenosis), Grade
      2 (33-66% stenosis) or Grade 3 (>66% stenosis). Involvement among the different
      lung regions was then compared. RESULTS: Fifteen patients ages 6 months to 17
      years were identified; one had surgical augmentation of the central pulmonary
      arteries and was excluded from the central (main, right and left) pulmonary
      artery analysis. The proximal LPA and RPA, but not the MPA, were significantly
      smaller than those of the control subjects (P<0.01). The proximal LPA was
      significantly smaller than the proximal RPA (P<0.01) in the Alagille group (0.55
      LPA:RPA ratio). Within the Alagille group, 75% of the lobar and segmental
      branches showed mild or no stenoses (Grade 1), 17% showed moderate stenosis
      (Grade 2) and 8% showed severe stenosis (Grade 3). While not statistically
      significant, the right lung demonstrated a greater percentage of Grades 2 and 3
      stenoses (28%, right vs. 20% left, P=0.1). The right middle and lingula lobes of
      both lungs showed more Grade 2 and 3 stenoses (33% upper/middle vs. 18% lower,
      P<0.01). CONCLUSION: We describe a common pattern pulmonary artery stenosis in
      Alagille patients consisting of severe proximal LPA stenosis, heavy involvement
      of the lobar and segmental branches (more often right than left), and a greater
      involvement of the upper lobes. Knowledge of this phenotypic pattern can help in
      the diagnosis of Alagille syndrome in patients presenting with pulmonary artery
      stenosis.

PMID- 27041278
TI  - Abnormal left ventricular relaxation and symptoms of heart failure.
AB  - OBJECTIVES: The purpose of our study was to assess the echocardiographic and
      angiographic parameters in patients with symptomatic heart failure (HF) and mild
      diastolic dysfunction (grade I). BACKGROUND: It remains uncertain why some
      patients with mild diastolic dysfunction exhibit HF symptoms and others are
      asymptomatic. METHODS: The study enrolled 80 hospitalized patients with impaired
      left ventricular (LV) relaxation. Patients were divided into two groups; one
      group had chronic functional class II to III dyspnea and the other group had no
      symptoms of HF. After admission, echocardiography and coronary angiography were
      performed for all patients and LV systolic and diastolic parameters were compared
      between the two groups. RESULTS: More patients in the asymptomatic group were
      hypertensive (p-value: 0.012). However, coronary artery disease was more
      prevalent in symptomatic patients (p-value: 0.022). The LV ejection fraction (EF)
      was significantly lower in symptomatic patients [median 54.33 %, 95 % confidence
      interval (53.76-54.87 %) in asymptomatic patients and median 49.43, 95 %
      confidence interval (47.23-50.91 %) in symptomatic patients, p-value <0.001].
      Furthermore, the systolic LV internal dimension was significantly larger in this
      group (p-value: 0.037). The results of logistic regression identified that only
      the absolute level of the LVEF was the negative determinant of the occurrence of
      HF in patients with impaired LV relaxation. CONCLUSION: Our study showed that LV
      systolic performance has an important role in occurrence of HF symptoms in
      patients with grade I diastolic dysfunction.

PMID- 27041279
TI  - Tetractinomyxon stages genetically consistent with Sphaerospora dicentrarchi
      (Myxozoa: Sphaerosporidae) found in Capitella sp. (Polychaeta: Capitellidae)
      suggest potential role of marine polychaetes in parasite's life cycle.
AB  - Known life cycles of myxosporean parasites have two hosts, but very few life
      cycles have been disclosed, especially in the marine environment. Sphaerospora
      dicentrarchi Sitja-Bobadilla and Alvarez-Pellitero, 1992 is a systemic parasite
      from the European seabass, Dicentrarchus labrax (Linnaeus, 1758), a highly
      valuable commercial fish. It affects its health, leading to aquaculture
      production losses. During 2013 and 2014, an actinospore survey was conducted in a
      total of 5942 annelids collected from a fish farm in Algarve and from the Aveiro
      Estuary, in Portugal. A new tetractinomyxon actinospore was found in a capitellid
      polychaete, belonging to the genera Capitella collected at the fish farm. The
      tetractinomyxons were pyriform measuring 11.1 +/- 0.7 um in length and 7.2 +/-
      0.4 um in width, and presented three rounded polar capsules measuring 2.4 +/- 0.3
      um in diameter. The molecular analysis of the 18S rRNA gene sequences from the
      tetractinomyxons revealed a similarity of 100% with the DNA sequences deposited
      in the GenBank from S. dicentrarchi myxospores collected from the European
      seabass and the spotted seabass in the same fish farm and 99.9% similarity with
      the DNA sequence obtained from the myxospores found infecting the European
      seabass in the Aveiro Estuary. Therefore, the new tetractinomyxons are inferred
      to represent the actinospore phase of the S. dicentrarchi life cycle.

PMID- 27041280
TI  - Molybdenum cofactor deficiency causes translucent integument, male-biased
      lethality, and flaccid paralysis in the silkworm Bombyx mori.
AB  - Uric acid accumulates in the epidermis of Bombyx mori larvae and renders the
      larval integument opaque and white. Yamamoto translucent (oya) is a novel
      spontaneous mutant with a translucent larval integument and unique phenotypic
      characteristics, such as male-biased lethality and flaccid larval paralysis.
      Xanthine dehydrogenase (XDH) that requires a molybdenum cofactor (MoCo) for its
      activity is a key enzyme for uric acid synthesis. It has been observed that
      injection of a bovine xanthine oxidase, which corresponds functionally to XDH and
      contains its own MoCo activity, changes the integuments of oya mutants from
      translucent to opaque and white. This finding suggests that XDH/MoCo activity
      might be defective in oya mutants. Our linkage analysis identified an association
      between the oya locus and chromosome 23. Because XDH is not linked to chromosome
      23 in B. mori, MoCo appears to be defective in oya mutants. In eukaryotes, MoCo
      is synthesized by a conserved biosynthesis pathway governed by four loci (MOCS1,
      MOCS2, MOCS3, and GEPH). Through a candidate gene approach followed by sequence
      analysis, a 6-bp deletion was detected in an exon of the B. mori molybdenum
      cofactor synthesis-step 1 gene (BmMOCS1) in the oya strain. Moreover,
      recombination was not observed between the oya and BmMOCS1 loci. These results
      indicate that the BmMOCS1 locus is responsible for the oya locus. Finally, we
      discuss the potential cause of male-biased lethality and flaccid paralysis
      observed in the oya mutants.

PMID- 27041281
TI  - [Perspectives of the Cell Therapy in Ophthalmology1. The Application of Stem
      Cells in the Regeneration of Damaged Surface of the Eye].
AB  - Regeneration of corneal epithelium is secured by a population of limbal stem
      cells (LSC), which are located in the basal part of the limbal epithelium.
      Deficiency in LSC leads to chronic inflammation, scarring and conjunctivization
      of cornea. Therapy of LSC deficiency consists in transplantation of limbal
      tissue, cultivated limbal epithelium or more recently in tranplantation of
      autologous cells including mesenchymal stem cells, oral mucosal epithelial cells
      or hair follicle-derived stem cells. A significant progress has been achieved in
      the field of cell therapy and also in the development of convenient scaffolds for
      the growth and transfer of cells on damaged cornea. KEY WORDS: ocular surface
      damage, stem cells, cell therapy.

PMID- 27041282
TI  - [Perspectives of the Cell Therapy in Ophthalmology.2. The Potential of Stem Cells
      for the Retinal Diseases Treatment].
AB  - Retinal diseases represent a large group of hereditary and acquired diseases that
      often lead to loss of vision. There is currently no effective treatment of
      retinal degeneration, only supportive therapy is used for treating numerous
      diseases. Perspective treatment of retinal diseases represent a cell therapy
      using stem cells. Suitable candidates for the stem cell therapy are mesenchymal
      stem cells due to their differentiating properties, protective effect and also
      immunomodulation. KEY WORDS: retinal disease, therapy, stem cells, mesenchymal
      stem cells.

PMID- 27041283
TI  - [The Clinical Signs of Experimental Autoimmune Uveitis].
AB  - INTRODUCTION: Autoimmune uveitis is a sight threatening disease which in many
      cases fails to respond to conventional immunosuppressive or biological therapy.
      The research in experimental models of autoimmune uveitis helps to find new
      therapeutical strategies. The aim of this study is to present the clinical and
      histological signs of experimental autoimmune uveitis (EAU) in mice. METHODS: EAU
      was induced in C57BL/6 mice by subcutaneous application of IRBP
      (interphotoreceptor retinoid binding protein) in complete Freunds adjuvant and
      intraperitoneal application of pertussis toxin. Clinical evaluation of uveitis
      was performed in vivo using special imaging system with otoscope. Histological
      evaluation of uveitis was performed at day 35 post induction of EAU on
      hematoxylin and eosin stained frozen sections. Clinical and histological grading
      was used to assess the inflammation intensity of EAU. RESULTS: The intensity of
      inflammation is depicted on representative fundus images and histological images
      of retina at day 35 post induction. CONCLUSION: The model of EAU is robust and
      reproducible and allows us to study the immunopathological mechanisms of
      inflammation and its regulation. The inflammatory signs in our model are similar
      to findings of posterior uveitis of autoimmune etiology in humans, thus we may
      apply our experimental results in human medicine.

PMID- 27041284
TI  - [Ocular Cicatricial Pemphigoid - a Retrospective Study].
AB  - INTRODUCTION: Ocular cicatricial pemphigoid (OCP) is rare, severe, sight
      threatening autoimmune disease of the conjunctiva, which affects elderly
      patients, more often women. AIM: To evaluate the success rate of stabilisation of
      ocular findings in patients with OCP. METHODS: Retrospective study of patients
      from Centre of Conjunctival and Corneal Diseases at Department of Ophthalmology,
      General University Hospital and 1st Medical Faculty of Charles University in
      Prague in 1992-2013 was performed. Frequency of OCP clinical stages, visual
      acuity (VA), disease activity and ocular complications of referred patients were
      monitored. Moreover, type of immunosuppressive (IS) therapy, the number of
      relapses of the disease and progress of OCP clinical stages were evaluated.
      Especially, we evaluated effects and side effects of mycophenolate mofetil (MM)
      therapy. In addition to that, type and frequency of ocular surgery that was
      carried out to the patients before and after the referral were recorded.
      Furthermore, we evaluated percentage of patients with mucous membranous
      pemphigoid (MMP). Also, the positive yield of diagnostic methods was assessed.
      RESULTS: The OCP was diagnosed and monitored in 51 patients (21 men and 30 women)
      during 21 years, the average age on the day of diagnosis was 68,4 years, the
      average period of observation was 57 months. 55 % of eyes were referred to our
      department at clinical stage 3, 27 % at stage 4. VA was maintained in 76 % of
      eyes, improved in 5 % of eyes and in 19 % of eyes deteriorated. Activity of OCP
      was detected during the first examination in 96 % of patients, the most common
      complications at that time was corneal ulcer or perforation. Patients were
      treated by immunosuppressive therapy, most often in combination: corticosteroids
      (47 patients), azathioprine (28 patients), cyclophosphamide (25 patients), MM (16
      patients), sulphasalazine (5 patients), dapsone (5 patients). We ascertained
      relapses in 40 % of patients. The progression to the next stage of OCP were found
      in 7 eyes (6,9 %) and 95 eyes (93,1 %) remained stable. Activity of disease was
      well controlled in 11 patients out of 16 (69 %) by MM, IS therapy of remain 5
      patients (31 %) had to be changed. Side effects of MM such as lymphopenia were
      present in 1 patient. Before OCP was diagnosed, patients underwent cataract
      surgery with the intraocular lens implantation, cryoepilation of eyelashes and
      eyelid plastic surgery, especially entropion. The most common indicated surgery
      in our clinic was amniotic membrane transplantation and retro position of
      muscular cutaneous leaf. 31 % of patients were diagnosed with MMP. Positive
      results of conjunctival biopsy were detected in 48 % from 42 examined samples and
      22 % from 32 examined samples had positive results of indirect immunofluorescence
      (anti-desmosoms). CONCLUSION: OCP diagnosis is established on the basis of
      patient's ophthalmic history and clinical findings. Positive results of direct
      and indirect immunofluorescence support the diagnosis. Activity of the disease
      and progression of OCP is effectively suppressed by systemic immunosuppressive
      therapy (for example MM), mainly if started at early stage of the disease. KEY
      WORDS: ocular cicatricial pemphigoid, immunosuppressive therapy, direct and
      indirect immunofluorescence, mycophenolate mofetil.

PMID- 27041285
TI  - [Clinical Tests Testing New Therapies for Stargardt Disease].
AB  - PURPOSE: To provide information on currently ongoing clinical trials for
      Stargardt disease. METHODS: We have searched the clinical trial register
      (www.clinicaltrials.gov) for the keyword "Stargardt" and list active ongoing
      studies. RESULTS: There are currently eight registered clinical trials enrolling
      patients with Stargardt disease; all in phase I or II aiming at four mechanisms
      of action: inhibition of the production of vitamin A toxic dimers, gene therapy
      restoring wild type transcription of the ABCA4 gene, neuroprotection preventing
      retinal cells from oxidative damage, and replacement of the damaged retinal
      pigment epithelium using stem cell therapy. The basic prerequisite for enrolment
      in the vast majority of clinical trials is confirmation of the clinical diagnosis
      by mutational analysis. CONCLUSION: The wide variety of therapies that are
      registered as clinical trials for Stargardt disease significantly raises the
      possibility that effective treatments will be available in the near future for
      this currently incurable condition and that molecular genetic testing should be
      increasingly considered. KEY WORDS: Stargardt disease, clinical trial, ABCA4,
      mutation.

PMID- 27041286
TI  - [Optic Disc Drusen and their Complications].
AB  - The aim of the study was to analyze the group of patients with optic disc drusen
      focusing on possible complications of this disease. MATERIAL AND METHODS: In our
      group of patients, we examined 46 eyes of 23 patients with the suspicion of optic
      disc drusen during the period from May 2013 until January 2014. In all adult
      patients, we examined the anterior and posterior segment of the eye
      biomicroscopically, established the visual acuity, measured the intraocular
      pressure, examined the visual field, performed the ultrasound examination of the
      eye (A and B-scan), analyzed the retinal nerve fiber layer (RNFL) by means of
      optic coherence tomography (OCT), and color and red-free photography. According
      to the biomicroscopical findings, the drusen were divided into invisible drusen
      (buried drusen) (verified by ultrasound only) - grade 0, visible delicate drusen 
      grade I, and multiple drusen (conglomerates) - grade II. RESULTS: Out of 23
      patients, 14 were women and 9 were men. The age of the patients ranged from 8 to
      82 years, the mean age was 44.4 years. In the group, there were 3 children (8,
      11, and 13 years). In twenty-two patients, the drusen were present bilaterally,
      and one female patient had drusen on the right eye only. The grade of the drusen
      was set from 0 to II in all 45 eyes according to their amount, location, and
      visibility. As grade 0 were evaluated drusen in 11 patients; out of them, 10
      patients had drusen bilaterally, and one female patient unilaterally. Out of
      these 11 patients, three were children. Grade I optic disc drusen bilaterally had
      nine patients, and three patients had drusen grade II bilaterally. In grade 0
      drusen, no defect of the visual field was noticed. In drusen grade I, it was
      noticed the defect of the visual field in two patients (four eyes) out of nine
      patients, and in grade II the defect was present in two out of three patients
      (three eyes). The evaluation of the RNFL, by means of OCT, was performed among
      all three groups according to their grade 0 - II. In higher grades, the thickness
      of the RNFL was lower. Comparing to drusen grade 0, the drusen grade I, and II
      presented serious thinning of the RNFL superiorly. In three patients (drusen
      grade 0 and I) other complications of the optic disc drusen were observed. In one
      female patient with drusen grade I, there was decrease of the visual acuity due
      to the partial intravitreal hemorrhage in her left eye and parapapillary located
      retinal hemorrhages. In one male patient with drusen grade 0 was bilateral
      decrease of the VA due to cystoid macular edema caused by drusen. This patient
      had also retinal hemorrhages located near the papilla and partial intravitreal
      hemorrhage in his worse left eye. In one female patient with the drusen grade 0,
      the tortuous veins were noticed. CONCLUSION: Drusen of the optic disc are present
      in 0.3 - 1.0 % of the population, and are bilateral in approximately 75 - 91 % of
      the cases. It is important to distinguish optic nerve disc drusen from the
      papiledema. Drusen of the optic nerve can cause severe defects of the visual
      field, decrease of the retinal nerve fiber layer, and may be accompanied by
      vessels complications. Patients with the optic disc drusen should regularly
      undergo ophthalmologic examinations focused on the intraocular pressure, visual
      field testing, and retinal fiber layer analysis. In patients with visual field
      defect and borderline values of intraocular pressure, the antiglaucomatic therapy
      is recommended. KEY WORDS: optic disc drusen, intraocular pressure, visual field,
      ultrasound, retinal nerve fiber layer analysis, complications of the optic disc
      drusen.

PMID- 27041287
TI  - [Bilateral Macular Edema Caused by Optic Disc Drusen - a Case Report].
AB  - In the case report, bilateral cystoid macular edema with optic disc edema on the
      left side in young man is described. As etiology out of the systemic diseases, we
      considered the hypertension. The results of the neurological examination,
      including the brain CT examination were physiological. The patient was examined
      by the internal specialist, the hypertension was treated - and it was the
      presumed etiology of the ophthalmologic findings. Due to the repeated worsening
      of the ophthalmologic findings, we searched for other etiology. Bilateral buried
      optic disc drusen were found by means of ultrasound. Bilateral cystoid macular
      edema and optic disc edema were evaluated as signs of circulatory disturbance of
      the posterior ciliary arteries and macular choroid caused by optic disc drusen.
      The antiglaucomatic treatment was started with - alpha 2 adrenergic receptors
      agonist - brimonidine - which increases the blood supply of the optic nerve and
      decreases the intraocular pressure with presumed delay of axons dysfunction. KEY
      WORDS: macular edema, optic disc drusen, intraocular pressure, visual field,
      ultrasound.

PMID- 27041290
TI  - In memoriam Leon Herszage (1931-2016).

PMID- 27041289
TI  - Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction.
AB  - Ivabradine inhibits hyperpolarization-activated cyclic nucleotide-gated channels
      in the sinus node, thereby reducing heart rate, and heart rate reduction improves
      regional myocardial blood flow and contractile function in ischemic myocardium.
      Accordingly, ivabradine reduces anginal symptoms in patients with stable coronary
      artery disease but does not improve their clinical outcome. Heart rate reduction
      with ivabradine in patients with symptomatic heart failure reduces symptoms,
      attenuates remodeling, and improves clinical outcome. In pigs and mice,
      ivabradine reduces infarct size from myocardial ischemia/reperfusion, even when
      heart rate reduction is abrogated by atrial pacing. Improved viability is also
      observed in isolated ventricular cardiomyocytes subjected to simulated
      ischemia/reperfusion. These beneficial effects are attributed to reduced reactive
      oxygen species formation from the mitochondria. There is also evidence for a
      heart rate-independent benefit from ivabradine in the vasculature of mice and
      humans, and in left ventricular contractile function of pigs. Finally, in mice,
      ivabradine also has anti-aging potential. 

PMID- 27041288
TI  - Nail Psoriasis: A Review of Treatment Options.
AB  - Nail involvement affects 80-90 % of patients with plaque psoriasis, and is even
      more prevalent in patients with psoriatic arthritis. This review is the result of
      a systemic approach to the literature and covers topical, intralesional,
      conventional systemic, and biologic systemic treatments, as well as non
      pharmacological treatment options for nail psoriasis. The available evidence
      suggests that all anti-tumor necrosis factor-alpha, anti-interleukin (IL)-17, and
      anti-IL-12/23 antibodies which are available for plaque psoriasis and psoriatic
      arthritis are highly effective treatments for nail psoriasis. Conventional
      systemic treatments, including methotrexate, cyclosporine, acitretin, and
      apremilast, as well as intralesional corticosteroids, can also be effective
      treatments for nail psoriasis. Topical treatments, including corticosteroids,
      calcipotriol, tacrolimus, and tazarotene, have also been shown to have a position
      in the treatment of nail psoriasis, particularly in mild cases. Finally, non
      pharmacological treatment options, including phototherapy, photodynamic therapy,
      laser therapy, and several radiotherapeutic options, are also reviewed but cannot
      be advised as first-line treatment options. Another conclusion of this review is
      that the lack of a reliable core set of outcomes measures for trials in nail
      psoriasis hinders the interpretation of results, and is urgently needed. 

PMID- 27041291
TI  - Bioactive compounds in banana and their associated health benefits - A review.
AB  - Banana is a very popular fruit in the world market and is consumed as staple food
      in many countries. It is grown worldwide and constitutes the fifth most important
      agricultural food crop in terms of world trade. It has been classified into the
      dessert or sweet bananas and the cooking bananas or plantains. It is either eaten
      raw or processed, and also as a functional ingredient in various food products.
      Banana contains several bioactive compounds, such as phenolics, carotenoids,
      biogenic amines and phytosterols, which are highly desirable in the diet as they
      exert many positive effects on human health and well-being. Many of these
      compounds have antioxidant activities and are effective in protecting the body
      against various oxidative stresses. In the past, bananas were effectively used in
      the treatment of various diseases, including reducing the risk of many chronic
      degenerative disorders. In the present review, historical background, cultivar
      classification, beneficial phytochemicals, antioxidant activity and health
      benefits of bananas are discussed. 

PMID- 27041292
TI  - Residue levels of five grain-storage-use insecticides during the production
      process of sorghum distilled spirits.
AB  - Residue levels of dichlorvos, fenitrothion, pirimiphos-methyl, malathion and
      deltamethrin during sorghum distilled spirits production were examined. The
      analytical method for these pesticides in sorghum, fermented sorghum, rice hull
      and distilled spirits was validated through linearity, matrix effect, accuracy
      and precision, limit of quantification (LOQ) and limit of detection (LOD)
      parameters. The pesticide residue levels before/after each process of soaking,
      steaming, fermentation, and distillation were determined by gas chromatography
      coupled with tandem mass spectrometry (GC-MS/MS). Results showed that soaking
      process could obviously reduce dichlorvos residue with 87% decrease as its high
      vapor pressure. The steaming process reduced pesticide residues by 42-83% mainly
      due to evaporation or thermal degradation. Also, the fermentation could remove
      pesticide residues by 40-63% in favor of biological degradation. Moreover, the
      distillation process was proved to be effective for decreasing the pesticide
      residues in distilled spirits with the processing factors lower than other
      processes for each pesticide. 

PMID- 27041293
TI  - Effect of controlled atmosphere storage on pericarp browning, bioactive compounds
      and antioxidant enzymes of litchi fruits.
AB  - 'Gola' litchi fruits were stored under ten different CA-combinations at 5+/-1
      degrees C to investigate its effects on pericarp browning, biochemical quality
      and antioxidative activities. Control fruit turned completely brown after 28days
      of storage and were excluded from the study. Fruit-stored under CA7-combination
      (1% O2+5% CO2) showed reduced weight loss, pericarp browning, membrane leakage
      and malondialdehyde contents. Soluble solid contents, titratable acidity and
      ascorbic acid contents were higher in CA7-stored fruit. Activities of catalase
      and superoxide dismutase enzymes, levels of total anthocyanins, DPPH radical
      scavenging-activity and phenolic contents were significantly higher in CA7-stored
      litchi fruit. In contrast, activities of polyphenol oxidase and peroxidase
      enzymes were substantially lower in fruit kept under CA7-combination. Fruit
      subjected to CA7-conditions also maintained higher organoleptic quality. In
      conclusion, 1% O2+5% CO2 CA-conditions delayed pericarp browning, maintained
      antioxidative activities and biochemical characteristics along with better
      organoleptic quality of litchi fruit for 35days. 

PMID- 27041294
TI  - Boar taint compound levels in back fat versus meat products: Do they correlate?
AB  - Surgical castration of male pigs will soon be abandoned, turning a major
      advantage of this practice, the elimination of boar taint, into the biggest
      challenge for pig industry when raising intact male pigs becomes common practice.
      To map the (economical) consequences in relation to boar-taint consumer
      acceptance, as well as offer a processing strategy for tainted carcasses to
      stockholders, the current study investigated not only back fat boar taint levels,
      but additionally generated information on the levels of boar taint compounds
      recovered after the production of commercially relevant meat products using UHPLC
      HRMS laboratory analysis. Our results demonstrate that levels of androstenone,
      skatole and indole in back fat and meat products tend to correlate strongly,
      particularly in fatty meat products (generally r>0.80). Concentration values in
      the edible (lean) meat fraction were significantly lower compared to back fat and
      fat sampled from fresh or processed meat (p<0.05). 

PMID- 27041295
TI  - Discrimination of honeys using colorimetric sensor arrays, sensory analysis and
      gas chromatography techniques.
AB  - Aroma profiles of six honey varieties of different botanical origins were
      investigated using colorimetric sensor array, gas chromatography-mass
      spectrometry (GC-MS) and descriptive sensory analysis. Fifty-eight aroma
      compounds were identified, including 2 norisoprenoids, 5 hydrocarbons, 4
      terpenes, 6 phenols, 7 ketones, 9 acids, 12 aldehydes and 13 alcohols. Twenty
      abundant or active compounds were chosen as key compounds to characterize honey
      aroma. Discrimination of the honeys was subsequently implemented using
      multivariate analysis, including hierarchical clustering analysis (HCA) and
      principal component analysis (PCA). Honeys of the same botanical origin were
      grouped together in the PCA score plot and HCA dendrogram. SPME-GC/MS and
      colorimetric sensor array were able to discriminate the honeys effectively with
      the advantages of being rapid, simple and low-cost. Moreover, partial least
      squares regression (PLSR) was applied to indicate the relationship between
      sensory descriptors and aroma compounds. 

PMID- 27041296
TI  - A new approach to synthesis of benzyl cinnamate: Optimization by response surface
      methodology.
AB  - In this work, the new approach to synthesis of benzyl cinnamate by enzymatic
      esterification of cinnamic acid with benzyl alcohol is optimized by response
      surface methodology. The effects of various reaction conditions, including
      temperature, enzyme loading, substrate molar ratio of benzyl alcohol to cinnamic
      acid, and reaction time, are investigated. A 5-level-4-factor central composite
      design is employed to search for the optimal yield of benzyl cinnamate. A
      quadratic polynomial regression model is used to analyze the experimental data at
      a 95% confidence level (P<0.05). The coefficient of determination of this model
      is found to be 0.9851. Three sets of optimum reaction conditions are established,
      and the verified experimental trials are performed for validating the optimum
      points. Under the optimum conditions (40 degrees C, 31mg/mL enzyme loading, 2.6:1
      molar ratio, 27h), the yield reaches 97.7%, which provides an efficient processes
      for industrial production of benzyl cinnamate. 

PMID- 27041297
TI  - Suitability of gamma irradiation for preserving fresh-cut watercress quality
      during cold storage.
AB  - The suitability of gamma irradiation (1, 2 and 5kGy) for preserving quality
      parameters of fresh-cut watercress (Nasturtium officinale R. Br.) during storage
      at 4+/-1 degrees C for 7d was investigated. The storage time decreased the
      protein content and the main carbohydrates, and increased the levels of malic and
      fumaric acids, sucrose and mono- and polyunsaturated fatty acids (MUFA and PUFA).
      The different irradiation doses did not caused any significant colour change. In
      general, the 2kGy dose favoured PUFA and was the most suitable to preserve the
      overall postharvest quality of fresh-cut watercress during cold storage. In turn,
      the 5kGy dose better preserved the antioxidant activity and total flavonoids and
      favoured MUFA, tocopherols and total phenolics, thus originating a final product
      with enhanced functional properties. Therefore, the suitability of gamma
      irradiation for preserving fresh-cut watercress quality during cold storage was
      demonstrated. 

PMID- 27041298
TI  - Preparation of stable food-grade double emulsions with a hybrid premix membrane
      emulsification system.
AB  - In this study we demonstrate that food-grade double emulsions can be successfully
      prepared using a hybrid premix emulsification system. A coarse emulsion
      containing beetroot juice as inner water phase, sunflower oil as oil phase and
      0.5% or 1.0% whey protein isolate solution as outer water phase was prepared
      using a rotor stator system. This emulsion was further refined, using a bed of
      glass beads (diameter 71MUm), through which the emulsion was pushed at different
      applied pressure (200-500kPa) and number of passes (1-5). All applied pressures
      lead to much smaller droplets while the juice remained encapsulated (>98%). The
      viscosity of the emulsions increased due to swelling of the internal water phase,
      and this implies that it is possible to encapsulate the components efficiently at
      relatively low internal water phase fraction at which the emulsions can be
      handled easily, while allowing them to obtain their final viscosity later. 

PMID- 27041299
TI  - Matrix compatible solid phase microextraction coating, a greener approach to
      sample preparation in vegetable matrices.
AB  - This work proposes the novel PDMS/DVB/PDMS fiber as a greener strategy for
      analysis by direct immersion solid phase microextraction (SPME) in vegetables.
      SPME is an established sample preparation approach that has not yet been
      adequately explored for food analysis in direct immersion mode due to the
      limitations of the available commercial coatings. The robustness and endurance of
      this new coating were investigated by direct immersion extractions in raw blended
      vegetables without any further sample preparation steps. The PDMS/DVB/PDMS
      coating exhibited superior features related to the capability of the external
      PDMS layer to protect the commercial coating, and showed improvements in terms of
      extraction capability and in the cleanability of the coating surface. In addition
      to having contributed to the recognition of the superior features of this new
      fiber concept before commercialization, the outcomes of this work serve to
      confirm advancements in the matrix compatibility of the PDMS-modified fiber, and
      open new prospects for the development of greener high-throughput analytical
      methods in food analysis using solid phase microextraction in the near future. 

PMID- 27041300
TI  - Benzaldehyde in cherry flavour as a precursor of benzene formation in beverages.
AB  - During sampling and analysis of alcohol-free beverages for food control purposes,
      a comparably high contamination of benzene (up to 4.6MUg/L) has been detected in
      cherry-flavoured products, even when they were not preserved using benzoic acid
      (which is a known precursor of benzene formation). There has been some
      speculation in the literature that formation may occur from benzaldehyde, which
      is contained in natural and artificial cherry flavours. In this study, model
      experiments were able to confirm that benzaldehyde does indeed degrade to benzene
      under heating conditions, and especially in the presence of ascorbic acid.
      Analysis of a large collective of authentic beverages from the market (n=170)
      further confirmed that benzene content is significantly correlated to the
      presence of benzaldehyde (r=0.61, p<0.0001). In the case of cherry flavoured
      beverages, industrial best practices should include monitoring for benzene.
      Formulations containing either benzoic acid or benzaldehyde in combination with
      ascorbic acid should be avoided. 

PMID- 27041301
TI  - Reduction in IgE reactivity of Pacific mackerel parvalbumin by heat treatment.
AB  - Parvalbumin, a major fish allergen, has been reported to be highly thermostable.
      However, little is known as to whether parvalbumin is stable at more than 100
      degrees C. Thermostability of the Pacific mackerel parvalbumin was examined by
      subjecting heated (20-140 degrees C) muscle extracts to SDS-PAGE, western
      blotting and ELISA. As judged by SDS-PAGE and western blotting with the anti
      parvalbumin antiserum recognizing the primary structure, the parvalbumin was not
      degraded even under severe heating conditions. However, western blotting analysis
      with the monoclonal antibody recognizing the stereoscopic structure revealed that
      the parvalbumin undergoes conformational changes in a heating load-dependent
      manner. Importantly, the IgE reactivity of the parvalbumin determined by ELISA
      using patient sera was also reduced in a heating load-dependent manner; complete
      loss of IgE reactivity was induced by heating at 140 degrees C. This study showed
      that the allergenicity of the Pacific mackerel parvalbumin is considerably less
      thermostable than assumed for other fish parvalbumins. 

PMID- 27041302
TI  - Enhancing oral bioavailability using preparations of apigenin-loaded W/O/W
      emulsions: In vitro and in vivo evaluations.
AB  - We analyzed the physical properties and digestibility of apigenin-loaded
      emulsions as they passed through a simulated digestion model. As the emulsion
      passed through the simulated stages of digestion, the particle size and zeta
      potential of all the samples changed, except for the soybean oil-Tween 80
      emulsion, in which zeta potential remained constant, through all stages,
      indicating that soybean oil-Tween 80 emulsions may have an effect on stability
      during all stages of digestion. Fluorescence microscopy was used to observe the
      morphology of the emulsions at each step. The in vivo pharmacokinetics revealed
      that apigenin-loaded soybean oil-Tween 80 emulsions had a higher oral
      bioavailability than did the orally administrated apigenin suspensions. These
      results suggest that W/O/W multiple emulsions formulated with soybean oil and
      tween 80 have great potential as targeted delivery systems for apigenin, and may
      enhance in vitro and in vivo bioavailability when they pass through the digestive
      tract. 

PMID- 27041303
TI  - Encapsulation of CO2 into amorphous alpha-cyclodextrin powder at different
      moisture contents - Part 2: Characterization of complexed powders and
      determination of crystalline structure.
AB  - This study aims to characterize CO2-alpha-cyclodextrin (alpha-CD) inclusion
      complexes produced from amorphous alpha-CD powder at moisture contents (MC) close
      to or higher than the critical level of crystallization (e.g. 13, 15 and 17% MC
      on wet basis, w.b.) at 0.4 and 1.6MPa pressure for 72h. The results of (13)C NMR,
      SEM, DSC and X-ray analyses showed that these MC levels were high enough to
      induce crystallization of CO2-alpha-CD complexed powders during encapsulation, by
      which amount of CO2 encapsulated by amorphous alpha-CD powder was significantly
      increased. The formation of inclusion complexes were well confirmed by results of
      FTIR and (13)C NMR analyses through an appearance of a peak associated with CO2
      on the FTIR (2334cm(-1)) and NMR (125.3ppm) spectra. Determination of crystal
      packing patterns of CO2-alpha-CD complexed powders showed that during
      crystallization, alpha-CD molecules were arranged in cage-type structure in which
      CO2 molecules were entrapped in isolated cavities. 

PMID- 27041304
TI  - Physicochemical properties and antioxidant potential of phosvitin-resveratrol
      complexes in emulsion system.
AB  - Egg yolk phosvitin is the most highly phosphorylated protein found in the nature.
      The physicochemical properties of phosvitin-resveratrol complexes and their
      synergistic antioxidant activities in microemulsions were investigated. The
      particle diameters of microemulsions containing 0.5%, 1.0% and 2.0% phosvitin
      were 2.660, 0.501 and 0.414MUm, respectively. The emulsifying activity index
      increased largely from 3.72 to 21.5m(2)/g with increasing phosvitin concentration
      from 0.5% to 2.0%. Fourier transform infrared spectroscopy and thermal analyses
      indicated that the microemulsions underwent a conformational change during
      homogenization. Antioxidant assays showed that phosvitin-resveratrol
      microemulsions exhibited a higher antioxidant activity than that of phosvitin
      resveratrol primary emulsions. The MTT assay indicated that HepG2 cell viability
      remained higher than 80% at phosvitin concentration below 1.0mg/ml. This
      suggested that phosvitin, when coupled with polyphenol, can effectively inhibit
      lipid oxidation in food emulsions, which provided valuable insights into deep
      processing and application of egg proteins in food industry. 

PMID- 27041305
TI  - An alternative method based on enzymatic fat hydrolysis to quantify volatile
      compounds in wheat bread crumb.
AB  - An alternative method to quantify 40 volatile compounds in wheat bread crumb is
      proposed. It consists of a Soxhlet extraction with a mixture of dichloromethane
      and diethyl ether containing lipases and a subsequent concentration with Vigreux
      column. It is the first time that lipases are added to transform the fat into
      free fatty acids and glycerol, which elute at the end of the chromatogram after
      the analytes, avoiding problems in the chromatography due to fat residues, such
      as dirtiness in the injector, column clogging or overlapping peaks. The extract
      is most easily analysed by GC/MS, using a standard addition method to correct
      matrix effect. The method was fully validated, with extraction efficiencies
      between 70% and 100% and precision RSD lower than 15%. The method was applied to
      a commercial crumb, with acetoin, phenylethyl alcohol and acetic acid as highly
      abundant compounds, which are considered main volatiles in crumb. 

PMID- 27041306
TI  - "Cut-off" effect of antioxidants and/or probes of variable lipophilicity in
      microheterogeneous media.
AB  - The activities of two hydrophilic (ascorbic acid and Trolox) and two hydrophobic
      (alpha-tocopherol and BHT) antioxidants were measured by reaction with a series
      of 4-alkanoyloxyTEMPO radical probes 1 in buffered (pH 7), aqueous, micellar
      solutions of reduced Triton-X 100. In all cases, a cut-off effect was observed,
      in line with previous observations of the same effect for the partitioning of
      probe series 1 in this medium. These results support an interpretation of the cut
      off effect in food emulsions, based on the "amphiphobic" nature of either the
      antioxidants or probes: competition between two molecular moieties, for the
      micellar hydrophobic core, tends to expose a reacting fragment differently to a
      more hydrophilic microenvironment, as the probe or antioxidant hydrophobicity
      increases. 

PMID- 27041307
TI  - Rapid assignment of malting barley varieties by matrix-assisted laser desorption
      ionisation - Time-of-flight mass spectrometry.
AB  - A method for discriminating malting barley varieties based on direct matrix
      assisted laser desorption-ionisation - time-of-flight mass spectrometry (MALDI
      TOF MS) fingerprinting of proteins was developed. Signals corresponding to
      hordeins were obtained by simple mixing of powdered barley grain with a MALDI
      matrix solution containing 12.5mgmL(-1) of ferulic acid in an
      acetonitrile:water:formic acid 50:33:17 v/v/v mixture. Compared to previous
      attempts at MALDI-TOF mass spectrometric analysis of barley proteins, the
      extraction and fractionation steps were practically omitted, resulting in a
      significant reduction in analytical time and costs. The discriminatory power was
      examined on twenty malting barley varieties and the practicability of the method
      was tested on sixty barley samples acquired from Pilsner Urquell Brewery. The
      method is proposed as a rapid tool for variety assignment and purity
      determination of malting barley that may replace gel electrophoresis currently
      used for this purpose. 

PMID- 27041308
TI  - Short-chain aliphatic ester synthesis using Thermobifida fusca cutinase.
AB  - Short-chain aliphatic esters are commonly used as fruit flavorings in the food
      industry. In this study, Thermobifida fusca (T. fusca) cutinase was used for the
      synthesis of aliphatic esters, and the maximum yield of ethyl caproate reached
      99.2% at a cutinase concentration of 50U/ml, 40 degrees C, and water content of
      0.5%, representing the highest ester yield to date. The cutinase-catalyzed
      esterification displayed strong tolerance for water content (up to 8%) and acid
      concentration (up to 0.8M). At substrate concentrations ?0.8M, the ester yield
      remained above 80%. Moreover, ester yields of more than 98% and 95% were achieved
      for acids of C3-C8 and alcohols of C1-C6, respectively, indicating extensive
      chain length selectivity of the cutinase. These results demonstrate the superior
      ability of T. fusca cutinase to catalyze the synthesis of short-chain esters.
      This study provides the basis for industrial production of short-chain esters
      using T. fusca cutinase. 

PMID- 27041309
TI  - Rice proteins, extracted by alkali and alpha-amylase, differently affect in vitro
      antioxidant activity.
AB  - Alkali treatment and alpha-amylase degradation are different processes for rice
      protein (RP) isolation. The major aim of this study was to determine the
      influence of two different extraction methods on the antioxidant capacities of
      RPA, extracted by alkaline (0.2% NaOH), and RPE, extracted by alpha-amylase,
      during in vitro digestion for 2h with pepsin and for 3h with pancreatin. Upon
      pepsin-pancreatin digestion, the protein hydrolysates (RPA-S, RPE-S), which were
      the supernatants in the absence of undigested residue, and the whole protein
      digests (RPA, RPE), in which undigested residue remained, were measured. RPE
      exhibited the stronger antioxidant responses to free radical scavenging activity,
      metal chelating activity, and reducing power, whereas the weakest antioxidant
      capacities were produced by RPE-S. In contrast, no significant differences in
      antioxidant activity were observed between RPA and RPA-S. The present study
      demonstrated that the in vitro antioxidant responses induced by the hydrolysates
      and the protein digests of RPs could be affected differently by alkali treatment
      and alpha-amylase degradation, suggesting that the extraction is a vital
      processing step to modify the antioxidant capacities of RPs. The results of the
      current study indicated that the protein digests, in which undigested residues
      remained, could exhibit more efficacious antioxidant activity compared to the
      hydrolysates. 

PMID- 27041310
TI  - Hydrophilic antioxidants from Andean tomato landraces assessed by their
      bioactivities in vitro and in vivo.
AB  - Potential nutraceutical properties of hydrophilic antioxidants in fruits of
      tomato landraces collected in Andean valleys were characterised. Antioxidant
      metabolites were measured by HPLC-DAD-MS/MS in mature fruits and their biological
      activities were assessed by in vitro and in vivo methods. In vitro antioxidant
      capacities were established by TEAC and FRAP methods. For in vivo biological
      activities we used a procedure based on Caenorhabditis elegans subjected to
      thermal stress. In addition, Saccharomyces cerevisiae was also used as a rapid
      screening system to evaluate tomato antioxidant capacity. All tomato accessions
      displayed significant differences regarding metabolic composition, biological
      activity and antioxidant capacity. Metabolite composition was associated with
      geographical origin and fruit size. Antioxidant activities showed significant
      association with phenolic compounds, such as caffeoylquinic acids, ferulic acid-O
      hexosides and rutin. Combination of in vitro and in vivo methods applied here
      allowed evaluation of the variability in nutraceutical properties of tomato
      landraces, which could be applied to other fruits or food products. 

PMID- 27041311
TI  - Optimization of pulsed ultrasound-assisted technique for extraction of phenolics
      from pomegranate peel of Malas variety: Punicalagin and hydroxybenzoic acids.
AB  - Pomegranate peel is a rich source of phenolic compounds (such as punicalagin and
      hydroxybenzoic acids). However, the content of such bioactive compounds in the
      peel extract can be affected by extraction type and condition. It was
      hypothesized that the optimization of a pulsed ultrasound-assisted extraction
      (PUAE) technique could result in the pomegranate peel extract with higher yield
      and antioxidant activity. The main goal was to optimize PUAE condition resulting
      in the highest yield and antioxidant activity as well as the highest contents of
      punicalagin and hydroxybenzoic acids. The operation at the intensity level of
      105W/cm(2) and duty cycle of 50% for a short time (10min) had a high efficiency
      for extraction of phenolics from pomegranate peel. The application of such short
      extraction can save the energy and cost of the production. Punicalagin and
      ellagic acid were the most predominant phenolic compounds quantified in the
      pomegranate peel extract (PPE) from Malas variety. PPE contained a minor content
      of gallic acid. 

PMID- 27041312
TI  - Nanoemulsions of thymol and eugenol co-emulsified by lauric arginate and
      lecithin.
AB  - Lauric arginate (LAE) is a cationic surfactant with excellent antimicrobial
      activities. To incorporate essential oil components (EOCs) in aqueous systems,
      properties of EOC nanoemulsions prepared with a LAE and lecithin mixture were
      studied. The LAE-lecithin mixture resulted in stable translucent nanoemulsions of
      thymol and eugenol with spherical droplets smaller than 100nm, contrasting with
      the turbid emulsions prepared with individual emulsifiers. Zeta-potential data
      suggested the formation of LAE-lecithin complexes probably through hydrophobic
      interaction. Negligible difference was observed for antimicrobial activities of
      nanoemulsions and LAE in tryptic soy broth. In 2% reduced fat milk, nanoemulsions
      showed similar antilisterial activities compared to free LAE in inhibiting
      Listeria monocytogenes, but was less effective against Escherichia coli O157:H7
      than free LAE, which was correlated with the availability of LAE as observed in
      release kinetics. Therefore, mixing LAE with lecithin improved the physical
      properties of EOC nanoemulsions but did not improve antimicrobial activities,
      especially against Gram-negative bacteria. 

PMID- 27041313
TI  - Sequence, taste and umami-enhancing effect of the peptides separated from soy
      sauce.
AB  - Five tasty peptides were separated from soy sauce, by sensory-guided
      fractionation, using macroporous resin, medium-pressure liquid chromatography and
      reverse phase-high performance liquid chromatography, and identified by ultra
      performance liquid chromatography tandem mass-spectrometry as ALPEEV, LPEEV,
      AQALQAQA, EQQQQ and EAGIQ (which originated from glycinin A1bB2-445, glycinin
      A1bB2-445, cobyric acid synthase, leucine-tRNA ligase and glycoprotein
      glucosyltransferase, respectively). LPEEV, AQALQAQA and EQQQQ tasted umami with
      threshold values of 0.43, 1.25 and 0.76mmol/l, respectively. ALPEEV and EAGIQ had
      minimal umami taste, but ALPEEV, EAGIQ and LPEEV showed umami-enhancement with a
      threshold estimated at 1.52, 1.94 and 3.41mmol/l, respectively. In addition, the
      synthetic peptides showed much better sensory taste than mixtures of their
      constitutive amino acids. It indicated that peptides might play an important role
      in the umami taste of soy sauce. 

PMID- 27041314
TI  - Super-chilling (-0.7 degrees C) with high-CO2 packaging inhibits biochemical
      changes of microbial origin in catfish (Clarias gariepinus) muscle during
      storage.
AB  - Controlled freezing-point storage (CFPS) is an emerging preservative technique
      desirable for fish. In the present study, catfish fillets were stored at -0.7
      degrees C under different packaging atmospheres: air (AP), vacuum (VP), and 60%
      CO2/40% N2 (MAP). Chemical, microbiological, and sensory analyses were performed
      during storage. Results showed the following descending order of chemical changes
      (degradation of nucleotides, conversion of protein to volatile-based nitrogen and
      biogenic amines, and production of trimethylamine nitrogen), as well as loss of
      sensory properties: 4 degrees C AP>-0.7 degrees C AP~4 degrees C VP>-0.7 degrees
      C VP~4 degrees C MAP>-0.7 degrees C MAP. The chemical changes were well
      correlated with microbial growth suggesting the microbiological pathways. Hence,
      CFPS at -0.7 degrees C in combination with high-CO2 MAP can effectively maintain
      the quality of fresh catfish meat compared to traditional preservation methods. 

PMID- 27041315
TI  - Identification and analysis of piperitone in red wines.
AB  - The present study concerns the search for new aroma compounds associated with the
      flavor of aged and prematurely aged red wines. Sensory descriptive analysis
      associated with gas chromatography-olfactometry was first performed to find
      specific odoriferous zones. One of the zones, reminiscent of mint, was found in
      red wines with a prune flavor. Thanks to several analytical approaches including
      preparative gas chromatography, p-menth-1-en-3-one (piperitone), has been
      identified in red wines. The olfactory detection threshold of this terpene
      reminiscent of mint was 0.9MUg/L in model hydroalcoholic solution and 70MUg/L in
      red wines. Chiral multidimensional GC-MS was used to show that piperitone was
      present mainly in the (R) form in red wines. The concentration of piperitone in
      aged red wines ranged from a few ng/L to 435ng/L, but the level was not linked to
      the age of the wine nor to its premature evolution. 

PMID- 27041316
TI  - A label free electrochemical immunosensor for sensitive detection of porcine
      serum albumin as a marker for pork adulteration in raw meat.
AB  - A label free electrochemical immunosensor for sensitive detection of porcine
      serum albumin (PSA) is reported in this work. The immunosensor was constructed by
      first electrochemically reducing 4-carboxyphenyl diazonium salt, which had been
      electrochemically generated in situ, to a stable 4-carboxyphenyl layer on carbon
      nanofiber-modified screen printed electrode. Antibodies were covalently attached
      onto the electrode using carbodiimide chemistry between the carboxylic groups of
      the 4-carboxyphenyl layer and amine groups of the antibody. Using the strong
      affinities of serum albumins towards anions, the increase in cathodic peak
      current in anionic redox probe after immunocomplex formation with antibodies was
      used for PSA detection. The reported immunosensor demonstrated a linear range
      from 0.5 to 500pg/mL for the measurement of PSA with detection limit of 0.5pg/mL
      in buffer solution. Cross-reactivity studies have shown excellent specificity
      with satisfactory recovery of PSA in fresh meat samples without the need of
      sample dilution. 

PMID- 27041317
TI  - Oleuropein hydrolysis in natural green olives: Importance of the endogenous
      enzymes.
AB  - The bitter taste of olives is mainly caused by the phenolic compound named
      oleuropein and the mechanism of its hydrolysis during the processing of natural
      green olives was studied. First, a rapid chemical hydrolysis of oleuropein takes
      place at a high temperature of 40 degrees C and at a low pH value of 2.8, but the
      chemical hydrolysis of the bitter compound is slow at the common range of pH for
      these olives (3.8-4.2). However, decarboxymethyl elenolic acid linked to
      hydroxytyrosol and hydroxytyrosol have been found in a high concentration during
      the elaboration of natural green olives. When olives were heated at 90 degrees C
      for 10min before brining, these compounds are not formed. Hence, the debittering
      process in natural green olives is due to the activity of beta-glucosidase and
      esterase during the first months of storage and then a slow chemical hydrolysis
      of oleuropein happens throughout storage time. 

PMID- 27041318
TI  - Angiotensin I-converting enzyme (ACE) inhibitory activity and structural
      properties of oven- and freeze-dried protein hydrolysate from fresh water fish
      (Cirrhinus mrigala).
AB  - The angiotensin I-converting enzyme (ACE) inhibitory activity and structural
      properties of oven-dried (OD-FPH) and freeze-dried (FD-FPH) protein hydrolysates
      derived from fresh water fish (Cirrhinus mrigala) muscle, using papain, were
      investigated. Amino acid profiles indicated a higher proportion of hydrophobic
      residues in OD-FPH and hydrophilic residues in FD-FPH samples. Fourier transform
      infrared (FT-IR) spectra revealed random coil structure in OD-FPH and beta-sheet
      in FD-FPH samples. The approximate molecular weight of peptides in OD-FPH and FD
      FPH was in the range of 7030-339Da. The IC50 values for ACE inhibition by OD-FPH
      and FD-FPH samples were found to be 1.15 and 1.53mg of proteinml(-1),
      respectively. The ACE-inhibitory activity of OD-FPH was more stable (during
      sequential digestion, using pepsin and pancreatin) than that of FD-FPH sample.
      The study suggested that the ACE inhibitory activity of protein hydrolysate was
      not affected by oven-drying. 

PMID- 27041319
TI  - Multivariate class modeling techniques applied to multielement analysis for the
      verification of the geographical origin of chili pepper.
AB  - Four class-modeling techniques (soft independent modeling of class analogy
      (SIMCA), unequal dispersed classes (UNEQ), potential functions (PF), and
      multivariate range modeling (MRM)) were applied to multielement distribution to
      build chemometric models able to authenticate chili pepper samples grown in
      Calabria respect to those grown outside of Calabria. The multivariate techniques
      were applied by considering both all the variables (32 elements, Al, As, Ba, Ca,
      Cd, Ce, Co, Cr, Cs, Cu, Dy, Fe, Ga, La, Li, Mg, Mn, Na, Nd, Ni, Pb, Pr, Rb, Sc,
      Se, Sr, Tl, Tm, V, Y, Yb, Zn) and variables selected by means of stepwise linear
      discriminant analysis (S-LDA). In the first case, satisfactory and comparable
      results in terms of CV efficiency are obtained with the use of SIMCA and MRM
      (82.3 and 83.2% respectively), whereas MRM performs better than SIMCA in terms of
      forced model efficiency (96.5%). The selection of variables by S-LDA permitted to
      build models characterized, in general, by a higher efficiency. MRM provided
      again the best results for CV efficiency (87.7% with an effective balance of
      sensitivity and specificity) as well as forced model efficiency (96.5%). 

PMID- 27041320
TI  - Oxygenated heterocyclic compounds to differentiate Citrus spp. essential oils
      through metabolomic strategies.
AB  - This study aimed to characterise and discriminate 44 authenticated commercial
      samples of citrus essential oils (EO) from seven species (bergamot, lemon,
      bigarade, orange, mandarin, grapefruit, lime) by analysing the non-volatile
      oxygenated heterocyclic compounds (OHC) by UHPLC/TOF-HRMS, multivariate data
      analysis (PCA, PLS-DA) and metabolomic strategies; the OHC fraction includes
      coumarins, furocoumarins, and polymethoxylated flavonoids. Two different
      approaches were adopted: (i) targeted profiling based on quantifying 18
      furocoumarins and coumarins, some of which are regulated by law, and (ii)
      targeted fingerprinting based on 140 OHCs reported in citrus essential oils, from
      which 38 discriminant markers were defined. This approach correctly discriminated
      the Citrus species; its "sensitivity" to relatively low adulteration rate (10%)
      was highly satisfactory. The proposed method is complementary to that of
      analysing the citrus EO volatile part by GC techniques. 

PMID- 27041321
TI  - Pinoresinol of olive oil decreases vitamin D intestinal absorption.
AB  - Enriching oils, such as olive oil, could be one solution to tackle the worldwide
      epidemic of vitamin D deficiency and to better fit with omega 3 (DHA)
      recommendations. However, data regarding the interactions occurring at the
      intestinal level between vitamin D and phenols from olive oil are scarce. We
      first determined the effect of polyphenols from a virgin olive oil, and a virgin
      olive oil enriched with DHA, on vitamin D absorption in rats. We then
      investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol
      and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols
      in the olive oil supplemented with DHA inhibited vitamin D postprandial response
      in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3
      polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to
      the presence of pinoresinol only. As the pinoresinol content can highly vary
      between olive oils, the present results should be taken into account to formulate
      an appropriate oil product enriched in vitamin D. 

PMID- 27041322
TI  - Anthocyanins influence tannin-cell wall interactions.
AB  - The rate of tannin extraction was studied in a vinification of red grapes and the
      results compared with another vinification made with white grapes fermented as
      for typical red wine, in the presence of skins and seeds. Even though the grapes
      presented a quite similar skin and seed tannin content, the differences in tannin
      concentration between both vinifications was very large, despite the fact that
      the only apparent difference between the phenolic composition of both wines was
      the anthocyanin content. This suggests that anthocyanins play an important role
      in tannin extractability, perhaps because they affect the extent of the tannin
      cell wall interaction, a factor that largely controls the resulting quantity of
      tannins in wines. To confirm this observation, the effect of anthocyanins on the
      tannin extractability from grape seeds and skin and on the interaction between
      tannins and grape cell walls suspended in model solutions were studied. The
      results indicated that anthocyanins favored skin and seed tannin extraction and
      that there is a competition for the adsorption sites between anthocyanins and
      tannins that increases the tannin content when anthocyanins are present. 

PMID- 27041323
TI  - Optimisation of an oak chips-grape mix maceration process. Influence of chip dose
      and maceration time.
AB  - Oak chips-related phenolics are able to modify the composition of red wine and
      modulate the colour stability. In this study, the effect of two maceration
      techniques, traditional and oak chips-grape mix process, on the phenolic
      composition and colour of Syrah red wines from warm climate was studied. Two
      doses of oak chips (3 and 6g/L) at two maceration times (5 and 10days) during
      fermentation was considered. Changes on phenolic composition (HPLC-DAD-MS),
      copigmentation/polymerisation (spectrophotometry), and colour (Tristimulus and
      Differential Colorimetry) were assessed by multivariate statistical techniques.
      The addition of oak chips at shorter maceration times enhanced phenolic
      extraction, colour and its stabilisation in comparison to the traditional
      maceration. On contrast, increasing chip dose in extended maceration time
      resulted in wines with lighter and less stable colour. Results open the
      possibility of optimise alternative technological applications to traditional
      grape maceration for avoiding the common loss of colour of wines from warm
      climate. 

PMID- 27041324
TI  - Free and glycosylated simple phenol profiling in Apulian Italian wines.
AB  - Free simple phenols have a significant role in defining the sensory and
      nutritional characteristics of wines, affecting the organoleptic profile and
      having positive effects on health, but glycosidically bound phenols can also be
      hydrolysed during the winemaking process, releasing the corresponding volatile
      compounds and making a possible contribution to the final sensory profile. In
      this work, application of on-line SPE liquid chromatography-high resolution mass
      spectrometry, operating in negative polarity with heated electrospray, allowed to
      detect over eighty free and glycosylated simple phenols in Primitivo di Manduria
      and Negroamaro wines. Sixty-one phenols, four of which phenolic glucosidic
      precursors, were quantified as having quantification limits ranging from 0.001 to
      0.1MUgmL(-1), calibration R(2) of 0.99 for over 92% of compounds, and precision
      (R.S.D.%) always lower than 12%. Twenty-four simple phenolic precursors were
      tentatively identified as hexoside, pentoside and hexoside-hexoside derivatives,
      on the basis of accurate mass, isotopic pattern and MS/MS fragmentation. 

PMID- 27041325
TI  - Straightforward strategy for quantifying rotundone in wine at ngL(-1) level using
      solid-phase extraction and gas chromatography-quadrupole mass spectrometry.
      Occurrence in different varieties of spicy wines.
AB  - This paper presents a straightforward methodology to quantify rotundone in wine
      at ngL(-1) level. This compound, responsible for the black pepper aromatic note,
      may have sensorial relevance in some wines due to its low odor threshold,
      estimated at only 16ngL(-1) in red wines. The proposed strategy is based on solid
      phase extraction and analysis by GC-MS. The detection limit value was 0.6ngL(-1),
      which is more than one order of magnitude below its odor threshold in wine.
      Matrix effects have not been found and a synthetic wine calibration was proposed.
      The precision of the method was evaluated in reproducibility terms, obtaining a
      very acceptable value (RSD 4%). The optimized and validated strategy was applied
      to quantify this molecule in thirty wines belonging to different varieties as
      Graciano, Maturana tinta, Schioppettino, Shiraz, Duras and Gamay. Two of these
      wines exhibited levels higher than 100ngL(-1). 

PMID- 27041326
TI  - Verifying the botanical authenticity of commercial tannins through sugars and
      simple phenols profiles.
AB  - Commercial tannins from several botanical sources and with different chemical and
      technological characteristics are used in the food and winemaking industries.
      Different ways to check their botanical authenticity have been studied in the
      last few years, through investigation of different analytical parameters. This
      work proposes a new, effective approach based on the quantification of 6
      carbohydrates, 7 polyalcohols, and 55 phenols. 87 tannins from 12 different
      botanical sources were analysed following a very simple sample preparation
      procedure. Using Forward Stepwise Discriminant Analysis, 3 statistical models
      were created based on sugars content, phenols concentration and combination of
      the two classes of compounds for the 8 most abundant categories (i.e. oak, grape
      seed, grape skin, gall, chestnut, quebracho, tea and acacia). The last approach
      provided good results in attributing tannins to the correct botanical origin.
      Validation, repeated 3 times on subsets of 10% of samples, confirmed the
      reliability of this model. 

PMID- 27041327
TI  - Fluorescence excitation-emission matrix spectroscopy as a tool for determining
      quality of sparkling wines.
AB  - Browning in sparkling wines was assessed by the use of excitation-emission
      fluorescence spectroscopy combined with PARAllel FACtor analysis (PARAFAC). Four
      different cava sparkling wines were monitored during an accelerated browning
      process and subsequently storage. Fluorescence changes observed during the
      accelerated browning process were monitored and compared with other conventional
      parameters: absorbance at 420nm (A420) and the content of 5-hydroxymethyl-2
      furfural (5-HMF). A high similarity of the spectral profiles for all sparkling
      wines analyzed was observed, being explained by a four component PARAFAC model. A
      high correlation between the third PARAFAC factor (465/530nm) and the commonly
      used non-enzymatic browning indicators was observed. The fourth PARAFAC factor
      (280/380nm) gives us also information about the browning process following a
      first order kinetic reaction. Hence, excitation-emission fluorescence
      spectroscopy, together with PARAFAC, provides a faster alternative for browning
      monitoring to conventional methods, as well as useful key indicators for quality
      control. 

PMID- 27041328
TI  - Corrigendum to "Novel liquid chromatography-mass spectrometry method for
      sensitive determination of the mustard allergen Sin a 1 in food" [Food Chem. 183
      (2015) 58-63].

PMID- 27041329
TI  - Corrigendum to "An inclusion complex of eugenol into beta-cyclodextrin:
      Preparation, and physicochemical and antifungal characterization" [Food Chem. 196
      (2016) 324-330].

PMID- 27041330
TI  - Classification of facial diagnosis gloss in Chinese medicine based on different
      algorithms.
AB  - OBJECTIVE: To design a face gloss classification model and to provide an
      automatic and quantitative approach for the diagnosis of Chinese medicine (CM)
      based on the face images. METHODS: To classify the face gloss images into two
      groups (gloss and non-gloss), feature extraction methods were applied to the
      original images. The original images were supposed to obtain a more ideal
      representation in which gloss information was better revealed in four color
      spaces [including red, green, blue (RGB), hue, saturation, value (HSV), Gray and
      Lab]. Principal component analysis (PCA), 2-dimensional PCA (2DPCA), 2
      directional 2-dimensional PCA [(2D)2PCA], linear discriminant analysis (LDA), 2
      dimensional LDA (2DLDA), and partial least squares (PLS) were used as the feature
      extraction methods of face gloss. k nearest neighbor was used as the
      classifification method. RESULTS: All the six feature extraction methods were
      useful in extracting information of face gloss, especially LDA, which had the
      best prediction accuracy in the 4 color spaces. The average accuracy of LDA in
      the Lab was 7%-10% higher than that of PCA, 2DPCA, (2D)2PCA and 2DLDA P<0.05).
      The prediction accuracy of LDA reached 98% in the Lab color space and showed
      practical usage in clinical diagnosis. The consistent rate between the CM experts
      and the facial diagnosis system was 81%. CONCLUSION: A computer-assisted
      classifification model was designed to provide an automatic and quantitative
      approach for the gloss diagnosis of CM based on the face images.

PMID- 27041331
TI  - Susceptible gene polymorphisms for blood stasis syndrome of coronary heart
      disease.
AB  - Coronary heart disease (CHD) is a typically polygenic and multi-factorial
      disease. Recent advances have proposed the hypothesis that multiple polymorphisms
      in the presence of environmental factors could act synergistically in the
      pathogenesis of CHD. Lots of gene polymorphisms related with CHD have been
      discovered by genome-wide linkage (in families) and association (in populations)
      studies. A key issue now is to move from mapping gene polymorphisms to
      pinpointing causal genes and variants, and to develop a molecular understanding
      of how these genes lead to CHD. New thinking needs to be brought in for resolving
      this problem. The benefifit of Chinese medicine (CM) in CHD has been proven by
      more and more clinical evidences. More importantly, linking CM syndrome
      differentiation and biomedical diagnosis might help further accurate
      stratifification of CHD patients for intervention selection. The epidemiological
      investigation has demonstrated that blood stasis syndrome (BSS) is the major CM
      syndrome type of CHD. BSS is a kind of pathological state caused by disturbance
      of blood circulation. Clinical studies indicate that the severity of BSS is
      related with the severity of CHD and BSS of CHD may be "one involved in multiple
      genes" with hereditary tendency. If BSS of CHD is polygenic and hereditary, gene
      polymorphisms may be one of the pathogens. There are some pilot researches to
      explore the association between gene polymorphisms and BSS of CHD. In this
      review, the current status of gene polymorphisms related with BSS of CHD and
      future perspectives are discussed.

PMID- 27041332
TI  - Research of Brucea javanica against cancer.
AB  - Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer
      modalities, has been widely used for treatment of various cancers. Based on
      researches over the last decades, authors briefly summarized its active
      constituents, molecular mechanisms and clinical application for cancer treatment.

PMID- 27041333
TI  - Controversies on the values for health instruments of Chinese medicine.
AB  - Currently, there are increasing debates on the necessity of health instruments in
      Chinese medicine (CM) emerging in China. This study aims to reevaluate its status
      and values. Analyzing the causes, limits, advantages, and properties characters
      of health instruments in CM, it is found that weak fundamental research,
      incomplete self-awareness, and complicated social factors are the primary causes
      of debates. A comprehensive analysis showed health instruments in CM have health
      evaluation benefits to people from a dominant Chinese culture, meet the
      requirements of cultural background, and bring long-term value to Chinese
      instrument researches. However, its values and status should be treated
      differently depending on various subtypes. Although little theoretical and
      practical evidences proved that patients-reported health instruments in CM should
      be proposed independently, the doctors- and nurses-reported questionnaires are
      necessary. With this in mind, the study group proposes the 'Chinese cultural
      instruments (CCIs)' and 'health-related CCIs'. The latter one aims to evaluate
      the health status of people in a dominant Chinese culture. The CCIs theory
      represents Chinese instrument researches on a larger regional and higher level,
      and resolves the debates on instruments between CM and Western medicine in China.
      Health instruments in CM bring more scientific and social benefits for Chinese
      instrument researches. However, it does not include cultural demands, and lacks
      scientific significance. CCIs have all its virtues, and add solutions to the
      latter's theory bottleneck and scientific debates, thus bringing increased
      benefits to clinical assessment in complementary and alternative medicine
      researches.

PMID- 27041334
TI  - Target shape perception and clutter rejection use the same mechanism in bat
      sonar.
AB  - Big brown bats (Eptesicus fuscus) emit frequency-modulated (FM) biosonar sounds
      containing two or more harmonic sweeps. Echoes from frontally located targets
      arrive with first and second harmonics intact, leading to focused delay images.
      Echoes from offside or distant objects arrive with the second harmonic relatively
      weaker (lowpass-filtered), leading to defocused images, which prevents their
      clutter interference effects (Bates et al. J Exp Biol 214:394-401, 2011).
      Realistic targets contain several glints at slightly different distances and
      reflect several echoes at correspondingly different delays. The bat registers the
      delay of the nearest glint's echoes in the time domain. The delays of echoes from
      the farther glints are registered in the frequency domain, from interference
      nulls in the spectrum. Lowpass-filtering of echoes directly affects the image of
      the nearest glint by defocusing the delay image. However, lowpass-filtering also
      is superimposed on the interference spectrum used to register the farther glints,
      which distorts the pattern of interference nulls, defocusing the farther glints
      inversely, in the spectral domain, before they are perceived as delays.
      Differences in blurring between time-domain and frequency-domain parts of images
      identifies separate computational paths to perceptually reconstruct objects and
      prevent interference from off-side or distant clutter.

PMID- 27041335
TI  - Prognostic implication of the tumor location according to molecular subtypes in
      axillary lymph node-positive invasive ductal cancer in a Korean population.
AB  - Previous studies have not considered the axillary lymph node status when
      investigating the prognostic role of tumor location according to each molecular
      subtype. The present study aimed to investigate the prognostic implication of
      tumor location according to each molecular subtype in Korean invasive ductal
      carcinoma (IDC) patients with axillary lymph node metastasis. Data from 7856
      Korean IDC women with axillary lymph node metastasis were retrospectively
      analyzed. According to tumor location, patients were divided into the following
      groups: upper-outer quadrant, lower-outer quadrant, upper-inner quadrant, lower
      inner quadrant (LIQ), and central group. Overall survival (OS) and breast cancer
      specific survival (BCSS) were evaluated according to tumor location and molecular
      subtype. A subgroup analysis based on tumor size categorization was also
      performed. The patients' mean age was 47.97 +/- 9.64 years, and the median follow
      up time was 90 months. The LIQ group showed significantly worse prognosis in OS
      and BCSS (76.4 and 83.3 %, respectively) compared with the other groups, which
      was only significant in human epidermal growth factor receptor 2 (HER2)
      overexpression and triple-negative (TN) subtypes. In the subgroup analysis
      according to tumor size, the LIQ group showed a significantly worse prognosis in
      OS and BCSS compared with the other groups, in HER2 and TN subtypes, and only in
      patients with more than T2 stage. In Korean IDC patients with axillary lymph node
      metastasis, LIQ tumor location was associated with poor prognosis among those
      with HER2 and TN molecular subtypes and especially in those with more than T2
      stage.

PMID- 27041336
TI  - Excited Electron Dynamics at Semiconductor-Molecule Type-II Heterojunction
      Interface: First-Principles Dynamics Simulation.
AB  - Excited electron dynamics at semiconductor-molecule interfaces is ubiquitous in
      various energy conversion technologies. However, a quantitative understanding of
      how molecular details influence the quantum dynamics of excited electrons remains
      a great scientific challenge because of the complex interplay of different
      processes with various time scales. Here, we employ first-principles electron
      dynamics simulations to investigate how molecular features govern the dynamics in
      a representative interface between the hydrogen-terminated Si(111) surface and a
      cyanidin molecule. Hot electron transfer to the chemisorbed molecule was observed
      but was short-lived on the molecule. Interfacial electron transfer to the
      chemisorbed molecule was found to be largely decoupled from hot electron
      relaxation within the semiconductor surface. While the hot electron relaxation
      was found to take place on a time scale of several hundred femtoseconds, the
      subsequent interfacial electron transfer was slower by an order of magnitude. At
      the same time, this secondary process of picosecond electron transfer is
      comparable in time scale to typical electron trapping into defect states in the
      energy gap. 

PMID- 27041337
TI  - Determination of Dynamics of Plant Plasma Membrane Proteins with Fluorescence
      Recovery and Raster Image Correlation Spectroscopy.
AB  - A number of fluorescence microscopy techniques are described to study dynamics of
      fluorescently labeled proteins, lipids, nucleic acids, and whole organelles.
      However, for studies of plant plasma membrane (PM) proteins, the number of these
      techniques is still limited because of the high complexity of processes that
      determine the dynamics of PM proteins and the existence of cell wall. Here, we
      report on the usage of raster image correlation spectroscopy (RICS) for studies
      of integral PM proteins in suspension-cultured tobacco cells and show its
      potential in comparison with the more widely used fluorescence recovery after
      photobleaching method. For RICS, a set of microscopy images is obtained by single
      photon confocal laser scanning microscopy (CLSM). Fluorescence fluctuations are
      subsequently correlated between individual pixels and the information on protein
      mobility are extracted using a model that considers processes generating the
      fluctuations such as diffusion and chemical binding reactions. As we show here
      using an example of two integral PM transporters of the plant hormone auxin, RICS
      uncovered their distinct short-distance lateral mobility within the PM that is
      dependent on cytoskeleton and sterol composition of the PM. RICS, which is
      routinely accessible on modern CLSM instruments, thus represents a valuable
      approach for studies of dynamics of PM proteins in plants. 

PMID- 27041338
TI  - Fully implantable hearing aid in the incudostapedial joint gap.
AB  - A fully implantable hearing aid is introduced which is a combined sensor-actuator
      transducer designed for insertion into the incudostapedial joint gap (ISJ). The
      active elements each consist of a thin titanium membrane with an applied
      piezoelectric single crystal. The effectiveness of the operating principle is
      verified in a temporal bone study. We also take a closer look at the influence of
      an implantation-induced increase in middle ear stiffness on the transducer's
      output. An assembly of the transducer with 1 mm thickness is built and inserted
      into six temporal bones. At this thickness, the stiffness of the annular ligament
      is considerably increased, which leads to a loss in functional gain for the
      transducer. It is assumed that a thinner transducer would reduce this effect. In
      order to examine the performance for a prospective reduced pretension, we
      increased the gap size at the ISJ by 0.5 mm by removing the capitulum of the
      stapes in four temporal bones. The TM is stimulated with a broadband multisine
      sound signal in the audiological frequency range. The movement of the stapes
      footplate is measured with a laser Doppler vibrometer. The sensor signal is
      digitally processed and the amplified signal drives the actuator. The resulting
      feedback is minimized by an active noise control least mean square (LMS)
      algorithm which is implemented on a field programmable gate array. The dynamic
      range and the functional gain of the transducer in the temporal bones are
      determined. The results are compared to measurements from temporal bones without
      ISJ extension and to the results of Finite Elements Model (FE model) simulations.
      In the frequency range above 2 kHz a functional gain of 30 dB and more is
      achieved. This proposes the transducer as a potential treatment for high
      frequency hearing loss, e.g. for patients with noise-induced hearing loss. The
      transducer offers sufficient results for a comprehensive application. Adaptations
      in the transducer design or surgical approach are necessary to cope with ligament
      stiffening issues. These cause insufficient performance for low frequencies under
      1 kHz.

PMID- 27041339
TI  - Morphological and molecular genetic diversity of Strongyluris calotis (Nematoda:
      Ascaridida: Heterakidae) in South East and East Asian lizards.
AB  - Strongyluris calotis is a heterakid nematode in the large intestine of agamid
      lizards (Reptilia: Sauria: Agamidae) from the Oriental Region. The standard light
      microscopic definition of the species counts the "caudal papillae" as 10 pairs on
      male worms. However, previous work from our group using scanning electron
      microscopy (SEM) on the heterakid from agamid lizards in Japan, Taiwan, and
      Singapore revealed that this counting contained a pair of phasmids and that two
      pairs of postcloacal papillae were completely fused to form a pair of united
      papillae, thus resulting in "10 pairs." In the present study, we examined S.
      calotis specimens from the Emma Gray's forest lizard, Calotes emma (Agamidae),
      living in the plain forest at low altitude, and the Vietnam false bloodsucker,
      Pseudocalotes brevipes (Agamidae), living in the mountainous forest at high
      altitude in the northern part of Vietnam. Using SEM, the arrangement of caudal
      papillae in male worms from an Emma Gray's forest lizard was found to be
      comparable to classical S. calotis specimens from agamid lizards collected in
      Japan, Taiwan, and Singapore. However, male worms from Vietnam false bloodsuckers
      did not have a pair of united papillae but had 10 pairs of independent caudal
      papillae with a pair of phasmids. Molecular genetic analyses of the ribosomal RNA
      gene (rDNA) of worms of the classical S. calotis morphotype from Japan and
      Singapore and two S. calotis morphotypes from Vietnam demonstrated absolutely
      identical nucleotide sequences of partial 18S rDNA (at least 1764 base pairs
      (bp)) and 5.8S rDNA (158 bp). However, intraspecific differences were detected in
      other regions of the rDNA, related to the geographical distribution of hosts
      regardless of morphotype: 97.8-98.5 % identity (443-446 bp/453 bp) in the
      internal transcribed spacer (ITS)-1 region, 96.6-98.0 % identity (425-431 bp/440
      bp) in the ITS-2 region, and 99.6-99.7 % identity (1149-1151 bp/1154 bp) in the
      28S rDNA. Thus, in the future, taxonomic relationships of S. calotis distributed
      widely in the Oriental Region as well as other nominal Oriental Strongyluris
      spp., currently six in number, need to be extensively explored based on molecular
      genetic analyses in addition to intensive morphological characterization. 

PMID- 27041340
TI  - Anticoccidial activities of Chitosan on Eimeria papillata-infected mice.
AB  - Eimeria spp. multiply within the intestinal tract causing severe inflammatory
      responses. Chitosan (CS), meanwhile, has been shown to exhibit anti-inflammatory
      activities in different experimental models. Here, we investigated the effect of
      CS on the outcome of inflammation caused by Eimeria papillata in the mouse
      intestine. Investigations were undertaken into the oocyst output in feces and
      developmental stages and goblet cells in intestinal tissue. Assays for lipid
      peroxidation, nitric oxide (NO), and myeloperoxidase (MPO) were also performed. T
      cells in intestinal tissue were counted using immunohistochemistry while total
      IgA in serum or intestinal wash was assayed using ELISA. In addition, mRNA
      expression of tumor necrosis factor alpha (TNF-alpha), transforming growth factor
      beta (TGF-beta), interleukin (IL)-10, and IL-4 were detected using real-time PCR.
      The data indicated a reduction in both oocyst output and in the number of
      parasite developmental stages following CS treatment, while the goblet cell
      hypoplasia in infected mice was also inhibited. CS decreased lipid peroxidation,
      NO, and MPO but did not alter the T cell count or IgA levels in comparison to the
      infected group. The expression of TNF-alpha and TGF-beta decreased but IL-10 and
      IL-4 increased after CS treatment in comparison to the non-treated infected
      group. In conclusion, CS showed anti-inflammatory and protective effects against
      E. papillata infection. 

PMID- 27041341
TI  - The numbers game: quantitative analysis of Neorickettsia sp. propagation through
      complex life cycle of its digenean host using real-time qPCR.
AB  - Bacteria of the genus Neorickettsia are obligate intracellular endosymbionts of
      parasitic flukes (Digenea) and are passed through the entire complex life cycle
      of the parasite by vertical transmission. Several species of Neorickettsia are
      known to cause diseases in domestic animals, wildlife, and humans. Quantitative
      data on the transmission of the bacteria through the digenean life cycle is
      almost completely lacking. This study quantified for the first time the abundance
      of Neorickettsia within multiple stages of the life cycle of the digenean
      Plagiorchis elegans. Snails Lymnaea stagnalis collected from a pond in North
      Dakota were screened for the presence of digenean cercariae, which were
      subsequently tested for the presence of Neorickettsia. Three L. stagnalis were
      found shedding P. elegans cercariae infected with Neorickettsia. These snails
      were used to initiate three separate laboratory life cycles and obtain all life
      cycle stages for bacterial quantification. A quantitative real-time PCR assay
      targeting the GroEL gene was developed to enumerate Neorickettsia sp. within
      different stages of the digenean life cycle. The number of bacteria significantly
      increased throughout all stages, from eggs to adults. The two largest increases
      in number of bacteria occurred during the period from eggs to cercariae and from
      6-day metacercariae to 48-h juvenile worms. These two periods seem to be the most
      important for Neorickettsia propagation through the complex digenean life cycle
      and maturation in the definitive host. 

PMID- 27041342
TI  - Wide genetic variations at 18S ribosomal RNA locus of Cyclospora cayetanensis
      isolated from Egyptian patients using high resolution melting curve.
AB  - A variable clinical picture of cyclosporiasis including gastrointestinal tract
      (GIT) symptomatic or asymptomatic beside extraintestinal consequences suggests a
      possibility of heterogenicity of Cyclospora cayetanensis. The present work aimed
      to explore the possibility of genetic variation of C. cayetanensis using high
      resolution melting (HRM) curve of polymerase chain reaction (PCR) amplified 18S
      rRNA genes. DNAs extracted from the stool samples of 70 cyclosporiasis patients
      were amplified and scanned by PCR/HRM curve. The results showed that there are
      four different genotypic profiles of C. cayetanensis with presence of mixed ones.
      Although Tm of all profiles was within the same range, they were discerned by
      plotting of the temperature-shifted florescence difference between normalized
      melting curves (dF/dT). Genotypic profile I was found alone in 40 % of patients
      and mixed with genotypic profile II and/or III in 25.7 % of patients, followed by
      genotypic profile II in 14.3 % then genotypic profile III and IV (10 % each). A
      significant relation was found between genotypic profiles and GIT symptomatic
      status as profile I and profile II were mostly detected in patients with acute
      GIT symptoms without or with chronic illness, respectively, while profile IV
      cases only were GIT asymptomatic. Statistical significance relations between
      genotypic profiles and age, gender, residence and oocyst shape index were
      determined. In conclusion, PCR/HRM proved a wide variation on C. cayetanensis
      genes that could be reflected on its pathogenic effects and explaining the
      variability of the clinical manifestations presented by cyclosporiasis patients. 

PMID- 27041343
TI  - The Quest for Golden Bananas: Investigating Carotenoid Regulation in a Fe'i Group
      Musa Cultivar.
AB  - The regulation of carotenoid biosynthesis in a high-carotenoid-accumulating Fe'i
      group Musa cultivar, "Asupina", has been examined and compared to that of a low
      carotenoid-accumulating cultivar, "Cavendish", to understand the molecular basis
      underlying carotenogenesis during banana fruit development. Comparisons in the
      accumulation of carotenoid species, expression of isoprenoid genes, and product
      sequestration are reported. Key differences between the cultivars include greater
      carotenoid cleavage dioxygenase 4 (CCD4) expression in "Cavendish" and the
      conversion of amyloplasts to chromoplasts during fruit ripening in "Asupina".
      Chromoplast development coincided with a reduction in dry matter content and
      fruit firmness. Chromoplasts were not observed in "Cavendish" fruits. Such
      information should provide important insights for future developments in the
      biofortification and breeding of banana. 

PMID- 27041344
TI  - Multiparameter Estimation in Voltammetry When an Electron Transfer Process Is
      Coupled to a Chemical Reaction.
AB  - Estimation of thermodynamic and kinetic parameters in electrochemical studies is
      usually undertaken via comparison of the experimental results with theory based
      on a model that mimics the experiment. The present study examines the credibility
      of transient d.c. and a.c. voltammetric theory-experiment comparisons for
      recovery of the parameters needed to model the ubiquitous mechanism when an
      electron transfer (E) reaction is followed by a chemical (C) step in the EC
      process ([Formula: see text]). The data analysis has been undertaken using
      optimization methods facilitated in some cases by grid computing. These
      techniques have been applied to the simulated (5% noise added) and experimental
      (reduction of trans-stilbene) voltammograms to assess the capabilities of
      parameter recovery of E(0) (reversible potential for the E step), k(0)
      (heterogeneous electron transfer rate constant at E(0)), alpha (charge transfer
      coefficient for the E step), and k(f) and k(b) (forward and backward rate
      constants for the C step) under different kinetic regimes. The advantages
      provided by the use of a.c. instead of d.c. voltammetry and data optimization
      methods over heuristic approaches to "experiment"-theory comparisons are
      discussed, as are the limitations in the efficient recovery of a unique set of
      parameters for the EC mechanism. In the particular experimental case examined
      herein, results for the protonation of the electrochemically generated stilbene
      dianion demonstrate that, notwithstanding significant advances in experiment and
      theory of voltammetric analysis, reliable recovery of the parameters for the EC
      mechanism with a fast chemical process remains a stiff problem.

PMID- 27041347
TI  - To put the patient in the best condition: integrating integrative therapies in
      critical care.

PMID- 27041345
TI  - Psychiatric symptoms of Turkish combat-injured non-professional veterans.
AB  - BACKGROUND: It is well-known that exposure to combat puts individuals at risk for
      developing adverse psychological problems, including posttraumatic stress
      disorder (PTSD), depression, anxiety, and health-related behaviour problems and
      that the presence of combat-related injury increases the risk for
      psychopathology. Little is known, however, about the consequences of combat among
      conscripted soldiers fighting against terrorism in their homeland. OBJECTIVE: The
      main aim of the current study was to examine the prevalence of probable PTSD,
      severity of PTSD symptoms, depression, anxiety, and PTSD-related functional
      impairment among Turkish combat-injured, non-professional veterans. In addition,
      investigated were also the possible differences among the symptoms of PTSD,
      depression, and anxiety of the veterans by the frequency of current cigarette and
      alcohol use. METHODS: A total of 366 male veterans were assessed by using a
      demographic information form, which obtained information about injury status and
      health behaviours, the Posttraumatic Stress Diagnostic Scale (PDS), and the Brief
      Symptom Inventory (BSI). Symptom frequency and multivariate analysis of variances
      (MANOVA) were used to analyse the data. RESULTS: The prevalence of probable PTSD
      was 46.7% (171) among Turkish veterans while 16.4% experienced severe depression
      and 18% experienced severe anxiety. "Upset at reminders (65.8%)" was the most
      common PTSD symptom. "Responsibilities related to home (48.4%)" was the most
      frequently reported PTSD-related functional impairment. Results indicated that
      veterans who smoke more than half a pack per day scored significantly higher in
      severity of PTSD symptoms, depression, and anxiety. Contrary to expectations,
      there was no significant difference in symptoms of PTSD, depression, and anxiety
      related to the frequency of current alcohol use. CONCLUSION: Turkish non
      professional veterans with physical injuries have serious psychiatric problems an
      average of 13 years after a combat experience. Psychiatric and psychosocial
      services to Turkish non-professional veterans are a substantial and ongoing need.

PMID- 27041354
TI  - Gamma knife radiosurgery for trigeminal neuralgia secondary to benign lesions.
AB  - BACKGROUND: Investigate the clinical outcomes of gamma knife radiosurgery (GKS)
      in patients with benign intracranial lesions and accompanying trigeminal
      neuralgia (TN). METHODS: From February 2002 to November 2011, 50 patients (11
      males, 39 females) underwent GKS for intracranial lesions accompanied by TN.
      Pathological diagnoses included meningioma in 30 patients, vestibular schwannoma
      in 11, trigeminal schwannoma in 7, epidermoid cyst in 1, and arteriovenous
      malformation in 1. Twenty-two (44%) had a lesion dominantly located in the middle
      fossa and 26 patients (52%) in the posterior fossa. Twenty-five (50%) patients
      complained of type I pain, and 18 patients (36%) suffered from type II pain. The
      other 7 patients (14%) presented with facial pain that could not be determined.
      Pain was assessed retrospectively by subjective descriptions and with the Barrow
      Neurological Institute pain intensity score before and after GKS. RESULTS: Tumor
      control was evaluated with magnetic resonance imaging in 44 (95.7%) of 46
      patients over a median follow-up period of 54.8 months (range, 13-142 months).
      Initial improvement in pain after GKS was observed in 46 (92%) patients. The
      percentage of patients with improved Barrow Neurological Institute score was
      73.5% at 1 year, 70.7% at 2 years, and 76.5% at 3 years. Complete pain relief at
      the final follow-up was achieved in 18 patients (36%). Pain recurred in 13
      patients (28.3%) after initial improvement. Pathological diagnosis, location of
      the lesion, and type of facial pain did not influence the initial pain response
      after GKS. Pain recurred more frequently in patients with meningioma than in
      those with schwannoma (P = .045). Type II pain showed better response to the
      treatment (P = .006). CONCLUSION: The majority of patients with facial pain
      secondary to a benign intracranial lesion showed improvement after GKS. However,
      a substantial proportion of the patients experienced incomplete pain relief and
      recurrence. GKS needs to be combined with an additional modality or the technique
      must be modified to achieve complete and durable pain control.

PMID- 27041353
TI  - Protein single-model quality assessment by feature-based probability density
      functions.
AB  - Protein quality assessment (QA) has played an important role in protein structure
      prediction. We developed a novel single-model quality assessment method-Qprob.
      Qprob calculates the absolute error for each protein feature value against the
      true quality scores (i.e. GDT-TS scores) of protein structural models, and uses
      them to estimate its probability density distribution for quality assessment.
      Qprob has been blindly tested on the 11th Critical Assessment of Techniques for
      Protein Structure Prediction (CASP11) as MULTICOM-NOVEL server. The official CASP
      result shows that Qprob ranks as one of the top single-model QA methods. In
      addition, Qprob makes contributions to our protein tertiary structure predictor
      MULTICOM, which is officially ranked 3rd out of 143 predictors. The good
      performance shows that Qprob is good at assessing the quality of models of hard
      targets. These results demonstrate that this new probability density distribution
      based method is effective for protein single-model quality assessment and is
      useful for protein structure prediction. The webserver of Qprob is available at:
      http://calla.rnet.missouri.edu/qprob/. The software is now freely available in
      the web server of Qprob. 

PMID- 27041355
TI  - Experimental polyethylene-hydroxyapatite carrier-based endodontic system: an in
      vitro study on dynamic thermomechanical properties, sealing ability, and
      measurements of micro-computed tomography voids.
AB  - The dynamic thermomechanical properties, sealing ability, and voids formation of
      an experimental obturation hydroxyapatite-reinforced polyethylene (HA/PE)
      composite/carrier system were investigated and compared with those of a
      commercial system [GuttaCore (GC)]. The HA/PE system was specifically designed
      using a melt-extrusion process. The viscoelastic properties of HA/PE were
      determined using a dynamic thermomechanical analyser. Human single-rooted teeth
      were endodontically instrumented and obturated using HA/PE or GC systems, and
      then sealing ability was assessed using a fluid filtration system. In addition,
      micro-computed tomography (MUCT) was used to quantify apparent voids within the
      root-canal space. The data were statistically analysed using one-way anova and
      post hoc tests. The HA/PE composite exhibited important modulus and damping
      changes with an increase of temperature. The HA/PE system was more flexible than
      GC as the modulus of GC appeared to be significantly higher than that of HA/PE as
      a result of the high positive glass transition temperature (Tg ). However, HA/PE
      and GC presented similar sealing abilities. In conclusion, because sealing
      ability and voids formation were comparable between the tested materials, the
      experimental HA/PE system may be considered a suitable alternative material for
      root-canal obturation. Moreover, HA/PE possesses specific viscoelastic behaviour
      and lower melting points, which may facilitate root-canal retreatments.

PMID- 27041356
TI  - Intrauterine embryo transfer with canine embryos cryopreserved by the slow
      freezing and the Cryotop method.
AB  - Canine embryos (8-cell to blastocyst stages) frozen-thawed using the slow
      freezing method with glycerol (four recipients) or dimethyl sulfoxide (three
      recipients) as a cryoprotectant and vitrified-warmed using the Cryotop method
      (five recipients) were surgically transferred into the unilateral uterine horn of
      recipient bitches. As a result, the morphology of embryos frozen-thawed using the
      slow-freezing method was judged to be normal, but no conception occurred in any
      of the recipient bitches. Two of the five bitches that received transferred
      embryos (morula to early blastocyst stages) vitrified-warmed using the Cryotop
      method became pregnant and produced normal pups (1/9 embryos, 11.1% and 1/6
      embryos, 17.0%). It was concluded that the Cryotop method was more appropriate
      for canine embryo cryopreservation than the slow-freezing method, which is used
      for the cryopreservation of embryos of other mammalian species. 

PMID- 27041357
TI  - Removal of Inserted BAC after linearizatiON (RIBON)-a novel strategy to excise
      the mini-F sequences from viral BAC vectors.
AB  - The bacterial artificial chromosome (BAC) technology has been a mainstay approach
      for generating recombinant viruses, and several methods for excision of the mini
      F sequences from the viral BAC vectors have been developed. However, these
      strategies either require complicated procedures or leave scars of inserted
      sequences. To overcome these problems, a new method to excise the mini-F
      sequences from viral BAC vectors based on the Removal of Inserted BAC after
      linearizatiON (RIBON) strategy was developed in this study for herpesvirus of
      turkeys (HVT). Enhanced green fluorescent protein (eGFP) DNA and the mini-F
      sequences were inserted into the gene encoding HVT thymidine kinase (TK) by
      homologous recombination in chicken embryo fibroblasts (CEFs), and the
      constructed HVT-BAC vector was used to transform Escherichia coli (pHVT-BAC). To
      remove the inserted eGFP and mini-F sequences, pHVT-BAC was linearized using a
      homing endonuclease I-SceI and used to cotransfect CEFs together with a plasmid
      containing the TK gene of HVT. The obtained viruses (44%) did not express eGFP,
      and DNA sequencing of isolated clones revealed that they were completely free of
      the inserted BAC sequences. Moreover, growth kinetics and plaque morphology of
      reconstituted viruses were comparable with those of the parental HVT. The results
      of this study demonstrate that the novel RIBON approach to remove mini-F
      sequences from the viral genome is simple and effective. 

PMID- 27041358
TI  - An intensive dispersion and synchronous assembly of single-walled carbon
      nanotubes in a surfactant-oil-water association system.
AB  - This paper reports a novel approach for achieving an intensive dispersion and
      synchronous assembly of single-walled carbon nanotubes (SWNTs) using a surfactant
      oil-water association system as medium. A kind of nonionic surfactant N,N-bis(2
      hydroxyethyl)dodecanamide (DDA) which could form a bi-continuous network
      structure not only in water but also in dodecane was used. The SWNTs were
      infiltrated into the dodecane-DDA mixture instead of DDA aqueous solution, and
      the attractive van der Waals forces between the pristine SWNT agglomerates were
      decreased in the first place; the thorough dispersion of the SWNTs was completed
      in the subsequent phase transformation by adjusting the oil/water ratio, along
      with mild sonication stirring. The individual SWNTs with different chiralities,
      such as (6,5), (7,5), (7,6), and (9,4), are all separated well after mild
      centrifugation treatment, which was confirmed by the well-resolved UV-Vis-NIR
      absorption and sharp fluorescence spectra. In particular, the self-assembly of
      DDA drove the separated individual SWNTs forming a large scale spatial network
      architecture. We believe that the SOW-SWNT suspension has high potential in
      constructing new functional materials by introducing diverse desirable components
      through the oil phase and also the water phase medium. 

PMID- 27041362
TI  - Quality of Adhesions After Sutured Paramedian vs. Laparoscopic Toggle Abomasopexy
      in an Ovine Model.
AB  - OBJECTIVE: To evaluate adhesions created by abomasopexies using either chromic
      gut or polydioxanone suture through a right paramedian approach and determine
      whether a laparoscopic toggle technique is an acceptable alternative to open
      abomasopexy using an ovine model. STUDY DESIGN: Experimental study. ANIMALS:
      Mature ewes (n=30). METHODS: Ewes received 1 of 3 abomasopexy techniques (n=10):
      right paramedian approach using chromic gut or polydioxanone, or a laparoscopic
      toggle technique. After euthanasia 8 weeks postoperatively, adhesions were
      removed en bloc and adhesion cross-sectional area (width * length) and depth
      (distance from abdominal wall to abomasum) were measured and given a grade of 0-3
      based on the quality of adhesion. Surgical time was recorded and compared for
      each technique. Significance was set at P<=.05. RESULTS: Abomasopexies performed
      with either suture material resulted in a significantly larger mean cross
      sectional area and higher adhesion grades compared to those performed using the
      toggle. Width and length of adhesions formed using chromic gut or polydioxanone
      were not significantly different; however, both were significantly wider and
      longer than those formed using the toggle. The laparoscopic toggle technique
      required significantly less surgical time than the sutured techniques.
      CONCLUSION: Polydioxanone is as effective as chromic gut suture material in
      inducing abomasal adhesion formation in our sheep model. The clinical
      significance of the size and grade of adhesions formed is unknown and requires
      further investigation before the laparoscopic toggle technique can be recommended
      as a replacement for paramedian abomasopexy in cattle for the treatment of
      displaced abomasum.

PMID- 27041363
TI  - Recent and emerging innovations in Salmonella detection: a food and environmental
      perspective.
AB  - Salmonella is a diverse genus of Gram-negative bacilli and a major foodborne
      pathogen responsible for more than a million illnesses annually in the United
      States alone. Rapid, reliable detection and identification of this pathogen in
      food and environmental sources is key to safeguarding the food supply.
      Traditional microbiological culture techniques have been the 'gold standard' for
      State and Federal regulators. Unfortunately, the time to result is too long to
      effectively monitor foodstuffs, especially those with very short shelf lives.
      Advances in traditional microbiology and molecular biology over the past 25 years
      have greatly improved the speed at which this pathogen is detected. Nonetheless,
      food and environmental samples possess a distinctive set of challenges for these
      newer, more rapid methodologies. Furthermore, more detailed identification and
      subtyping strategies still rely heavily on the availability of a pure isolate.
      However, major shifts in DNA sequencing technologies are meeting this challenge
      by advancing the detection, identification and subtyping of Salmonella towards a
      culture-independent diagnostic framework. This review will focus on current
      approaches and state-of-the-art next-generation advances in the detection,
      identification and subtyping of Salmonella from food and environmental sources.

PMID- 27041364
TI  - Half-dose ganciclovir preemptive treatment of cytomegalovirus infection after
      pediatric allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Ganciclovir (GCV) has been widely used as preemptive therapy after
      hematopoietic stem cell transplantation (HSCT), although bone marrow suppression
      is a known accompaniment, with secondary infection or bleeding as potential
      complications. Our aim was to evaluate clinical outcomes in pediatric patients
      with low cytomegalovirus (CMV) antigenemia levels using half the dosage of GCV
      generally given preemptively. METHODS: Patients received half doses of
      intravenous GCV (5 mg/kg once daily, 6 days/week) at CMV antigenemia levels
      <10/200,000 cells. At higher levels of CMV antigenemia, conventional doses of GCV
      (5 mg/kg every 12 h) were administered. RESULTS: A total of 130 patients were
      evaluated, detecting CMV antigenemia in 87 (66.9%). Of these patients, 74 (85.1%)
      were treated preemptively with half-dose GCV, which proved effective as sole
      therapy in 51 (68.9%). CMV retinitis developed in 4 patients, 2 of whom initially
      were given half-dose GCV. All infections resolved successfully, with no CMV
      related deaths. CMV seropositivity in recipients was the only significant risk
      factor for positive CMV antigenemia (hazard ratio [HR] = 10.05, P = 0.046).
      Compared with half-dose GCV administration, conventional GCV dosing resulted in a
      higher rate of severe neutropenia, defined as absolute neutrophil count <0.5 *
      10(9) /L (HR = 4.30, P = 0.015). CONCLUSION: Half-dose GCV therapy at CMV
      antigenemia levels <10/200,000 cells is an effective and safe means of
      preemptively treating pediatric CMV infection after HSCT.

PMID- 27041365
TI  - Use of Everolimus-based Immunosuppression to Decrease Cytomegalovirus Infection
      After Kidney Transplant.
AB  - OBJECTIVES: Cytomegalovirus infection and disease remain an issue in solid-organ
      transplant. Universal prophylaxis is more cost-effective than a preemptive
      strategy and is associated with significantly less Cytomegalovirus resistance
      after kidney transplant, especially in Cytomegalovirus-seropositive donors and
      Cytomegalovirus-seronegative recipients. MATERIALS AND METHODS: Registry data and
      meta-analyses have shown that mammalian target of rapamycin inhibitors (sirolimus
      and everolimus-based immunosuppression) are associated with significantly less
      Cytomegalovirus events in de novo kidney transplant patients than in patients who
      are treated with calcineurin inhibitors plus mycophenolate-based
      immunosuppression. RESULTS: Recent pooled analyses of 3 randomized controlled
      trials in de novo kidney transplant patients, where immunosuppression was based
      on cyclosporine with either mycophenolate or everolimus, showed that patients who
      received everolimus had significantly less Cytomegalovirus events
      (Cytomegalovirus viremia, Cytomegalovirus infection/disease) than those who
      received mycophenolate, with or without cytomegalovirus as prophylaxis. An even
      more recent prospective randomized controlled study on de novo kidney transplant
      patients with no anticytomegalovirus prophylaxis demonstrated that everolimus
      based immunosuppression plus low-dose tacrolimus was associated with
      significantly less Cytomegalovirus infection than standard-dose tacrolimus plus
      mycophenolate. CONCLUSIONS: The potential benefits are not fully known of such a
      therapeutic strategy to limit the long-term indirect effects mediated by
      Cytomegalovirus infections.

PMID- 27041366
TI  - A Case of Eczematoid Graft-Versus-Host Disease.
AB  - A 13-year-old boy underwent allogeneic hematopoietic stem cell transplantation
      (HSCT) for underlying acute lymphoblastic leukemia and achieved neutrophil
      engraftment 28 days after HSCT. He developed ichthyosis 6 weeks after HSCT and
      then keratotic follicular papules, palmoplantar keratoderma, and a seborrheic
      dermatitis-like eruption 18 weeks after HSCT. From skin biopsies he was diagnosed
      with eczematoid graft-versus host disease (GVHD), which showed spongiosis with
      scattered necrotic keratinocytes. He responded to oral and topical steroids and
      an increase in cyclosporine dose. Although uncommon, eczematoid GVHD must be
      considered in children who have undergone HSCT and then develop an atypical
      eczematous eruption, especially in the absence of a history of atopy.

PMID- 27041367
TI  - Synthesis of a poly(ethylene glycol) galloyl sensitizer tip for an 'all-in-one'
      photodynamic device.
AB  - This paper describes the synthesis of a specialized silica tip for an optical
      fiber device capable of delivering all components necessary for photodynamic
      therapy. Oxygen, light and a cleavable tripolyethylene glycol (PEG)-galloyl
      pheophorbide sensitizer are simultaneously delivered by the silica tip, where the
      tip was synthesized in six steps. A comparison of synthetic steps to reach
      PEGylated sensitizers bound to fluorinated silica and a previously reported
      Teflon/polyvinyl alcohol (PVA) nanocomposite ( Ghosh, G. et al. J. Phys. Chem. B
      2015, 119, 4155- 4164) was made. The hydrolytic stability of the attached PEGs
      and the extent to which the PEG groups enhance solubility will also be discussed.
      The new triPEG-galloyl sensitizer has the potential for use in intraoperative
      pointsource photodynamic therapy which aims for precision treatment of residual
      disease. Schematic of the synthesis of a photoactive silica surface. It is
      composed of fluorinated silica connected to a photo-releasable sensitizer with
      short-chain PEGs.

PMID- 27041368
TI  - Fixed Drug Eruption Due to Selective Hypersensitivity to Naproxen with Tolerance
      to other Propionic Acid NSAIDs.
AB  - BACKGROUND: Naproxen is a non-steroidal anti-inflammatory drug (NSAID), belonging
      to propionic acid group, and its chemical structure is a 6-metoxi-metil-2
      naftalenoacetic acid. Fixed drug eruptions (FDE) have been rarely reported.
      OBJECTIVE: A 38-year-old woman referred that after 2 hours of taking 2 tablets of
      naproxen for a headache, she developed several edematous and dusky-red macules,
      one on right forearm and the other two in both thighs and she was diagnosed with
      FDE probably due to naproxen. METHODS: We performed patch testing (PT) (Nonweven
      Patch Test Strips Curatest(r) Lohman & Rauscher International, Rangsdorf,
      Germany), with ibuprofen (5% Petrolatum), ketoprofen (2.5% Petrolatum), naproxen
      and nabumetone (both 10% in DMSO) on the residual lesion of the forearm with
      naproxen and in both thighs with ibuprofen, ketoprofen and nabumetone. RESULTS:
      Readings at day 1 (D1) and day 2 (D2) showed negative results to ibuprofen,
      ketoprofen and nabumetone, but were positive to naproxen in D1. A single blind
      oral challenge test (SBOCT) with other propionic acid derivates were performed in
      order to check for crossreactivity between them: ibuprofen, ketoprofen and
      nabumetone were administered and all drugs were well tolerated. CONCLUSION: In
      our patient PT confirmed the diagnosis and allowed us to study the cross
      reactivity between NSAIDs of the same group, and confirmed by SBOCT. Cross
      reactivity between propionic acid derivatives was studied. This is a case of
      hypersensitivity to naproxen with good tolerance to other propionic acids NSAIDs
      (ibuprofen and ketoprofen) and nabumetone, confirmed by PT and SBOCT. Some
      relavent patents for fixed drug eruption are discussed.

PMID- 27041369
TI  - The R130S mutation significantly affects the function of prestin, the outer hair
      cell motor protein.
AB  - A missense mutation, R130S, was recently found in the prestin gene, SLC26A5, of
      patients with moderate to severe hearing loss (DFNB61). In order to define the
      pathology of hearing loss associated with this missense mutation, a recombinant
      prestin construct harboring the R130S mutation (R130S-prestin) was generated, and
      its functional consequences examined in a heterologous expression system. We
      found that R130S-prestin targets the plasma membrane but less efficiently
      compared to wild-type. The voltage operating point and voltage sensitivity of the
      motor function of R130S-prestin were similar to wild-type prestin. However, the
      motor activity of R130S-prestin is greatly reduced at higher voltage stimulus
      frequencies, indicating a reduction in motor kinetics. Our study thus provides
      experimental evidence that supports a causal relationship between the R130S
      mutation in the prestin gene and hearing loss found in patients with this
      missense mutation. KEY MESSAGE: Membrane targeting of prestin is impaired by the
      R130S missense mutation. The fast motor kinetics of prestin is impaired by the
      R130S missense mutation. Our study strongly suggests that the prestin R130S
      missense mutation is pathogenic.

PMID- 27041370
TI  - Inflammation in Lafora Disease: Evolution with Disease Progression in Laforin and
      Malin Knock-out Mouse Models.
AB  - Lafora progressive myoclonus epilepsy (Lafora disease, LD) is a fatal rare
      autosomal recessive neurodegenerative disorder characterized by the accumulation
      of insoluble ubiquitinated polyglucosan inclusions in the cytoplasm of neurons,
      which is most commonly associated with mutations in two genes: EPM2A, encoding
      the glucan phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase
      malin. The present study analyzes possible inflammatory responses in the mouse
      lines Epm2a -/- (laforin knock-out) and Epm2b -/- (malin knock-out) with disease
      progression. Increased numbers of reactive astrocytes (expressing the GFAP
      marker) and microglia (expressing the Iba1 marker) together with increased
      expression of genes encoding cytokines and mediators of the inflammatory response
      occur in both mouse lines although with marked genotype differences. C3ar1 and
      CxCl10 messenger RNAs (mRNAs) are significantly increased in Epm2a -/- mice aged
      12 months when compared with age-matched controls, whereas C3ar1, C4b, Ccl4,
      CxCl10, Il1b, Il6, Tnfalpha, and Il10ra mRNAs are significantly upregulated in
      Epm2b -/- at the same age. This is accompanied by increased protein levels of IL1
      beta, IL6, TNFalpha, and Cox2 particularly in Epm2b -/- mice. The severity of
      inflammatory changes correlates with more severe clinical symptoms previously
      described in Epm2b -/- mice. These findings show for the first time increased
      innate inflammatory responses in a neurodegenerative disease with polyglucosan
      intraneuronal deposits which increase with disease progression, in a way similar
      to what is seen in neurodegenerative diseases with abnormal protein aggregates.
      These findings also point to the possibility of using anti-inflammatory agents to
      mitigate the degenerative process in LD.

PMID- 27041371
TI  - Killing of Vibrio cholerae and Escherichia coli Strains Carrying D-mannose
      sensitive Ligands by Mytilus Hemocytes is Promoted by a Multifunctional Hemolymph
      Serum Protein.
AB  - In aquatic environments, bivalve mollusks represent an important ecological niche
      for microorganisms. Persistence of bacteria in bivalve tissues partly depends on
      their capacity to survive the bactericidal activity of the hemolymph due to both
      cellular (hemocyes) and soluble serum factors (e.g., enzymes, lectins, opsonins).
      The extrapallial protein (EP) present in serum of Mytilus galloprovincialis
      (MgEP) has been recently shown to work as an opsonin promoting D-mannose
      sensitive (MS) interactions of the bivalve pathogen Vibrio aestuarianus 01/032
      strain with the hemocytes. In this study, the role of MgEP in adhesion and
      killing of other bacteria carrying MS sensitive ligands was investigated. MgEP
      enhanced adhesion to and killing by hemocytes of Vibrio cholerae ElTor N16961,
      expressing the MS hemagglutin (MSHA), as well as of Escherichia coli MG1655,
      carrying type 1 fimbriae. These results further support the recent finding that
      the multifunctional MgEP also acts as an opsonin involved in mussel defense
      towards bacteria carrying MS ligands. In addition, these results contribute to
      elucidate the ecology of bacterial pathogens that can be transmitted to humans
      via shellfish consumption.

PMID- 27041372
TI  - Masked Hypertension: How to Identify and When to Treat?
AB  - Approximately one out of 7-8 individuals with normal blood pressure (BP) in the
      clinic or doctor's office and one third of patients with chronic kidney disease
      with normal clinic BP have elevated ambulatory BP (masked hypertension). Patients
      with masked hypertension have an increased risk for target organ damage and a two
      fold increased risk for cardiovascular events compared to patients with normal
      clinic and ambulatory BP. Despite this elevated risk for adverse outcomes,
      patients with masked hypertension have been excluded from hypertension trials
      because of their normal clinic BP. It is still unknown whether the reduction in
      target organ damage and adverse cardiovascular outcomes associated with treatment
      of hypertension extends to patients with masked hypertension. Ongoing and planned
      interventional studies will provide an answer to this crucial question in a few
      years. At present, it seems reasonable to follow the suggestion of current
      European guidelines, that lifestyle measures and drug treatment should be
      considered in the presence of masked hypertension. 

PMID- 27041373
TI  - Lateral temporal encephaloceles: case-based review.
AB  - PURPOSE: Lateral temporal encephalocele is an extremely rare clinical condition,
      with only 18 cases presented in the literature to date. No review articles have
      examined lateral temporal encephalocele in depth. We therefore reviewed past
      cases of lateral encephalocele to clarify the clinical characteristics of this
      extremely rare deformity. We also present a case of lateral encephalocele with
      arachnoid cyst which has never been reported in past reports. METHODS: We
      identified 8 reports describing 18 cases of lateral temporal encephalocele. We
      therefore reviewed 19 cases of lateral temporal encephalocele, including our own
      experience, and discussed the clinical characteristics of this pathology.
      RESULTS: All the cases with lateral temporal encephalocele were detected at birth
      except for an occult case. The majority occurred at the pterion, and occurrence
      at the asterion appears much rarer. Due to the preference for the pterion, the
      ipsilateral orbital wall was also distorted in some cases. Lateral temporal
      encephalocele seems to have fewer associated malformations: only 3 cases of
      lateral temporal encephalocele had associated malformations, including our case
      which was associated with intracranial arachnoid cyst. The only case of lateral
      temporal encephalocele to have shown hydrocephalus was our own case. Patients
      with this deformity have relatively good prognoses: only 3 of the 19 cases showed
      delayed psychomotor development during follow-up. CONCLUSIONS: Provision of
      adequate treatment is likely to achieve a good prognosis in patients with lateral
      temporal encephalocele, so we should keep in mind this deformity when
      encountering pediatric patients with mass lesions on the temporal cranium.

PMID- 27041374
TI  - Spasticity secondary to Leigh syndrome managed with selective dorsal rhizotomy: a
      case report.
AB  - PURPOSE: Selective dorsal rhizotomy (SDR) is a surgical technique used to treat
      spasticity in children secondary to cerebral palsy (CP). METHOD: We report, to
      the best of our knowledge for the first time, the case of a child who underwent
      SDR for the management of spasticity secondary to Leigh syndrome. RESULT: SDR
      resulted in excellent functional outcome with significant improvement in
      spasticity. This result contributes to the mounting evidence that SDR could be
      used to alleviate spasticity secondary not only to CP but also to other
      pathologies as well.

PMID- 27041375
TI  - Endoscopic third ventriculostomy for hydrocephalus in brainstem glioma: a case
      series.
AB  - OBJECT: A brainstem glioma is an incurable brain tumor that can be complicated by
      hydrocephalus. A ventriculoperitoneal (VP) shunt is generally performed for the
      control of hydrocephalus. This study aimed to reveal the safety and efficacy of
      an endoscopic third ventriculostomy (ETV) for hydrocephalus in brainstem gliomas.
      METHODS: Six patients who had pontine glioma with hydrocephalus underwent an ETV
      between May 2010 and November 2015. In all the cases, there were one or more
      symptoms of hydrocephalus (headache, nausea, vomiting, or lethargy).
      Retrospective review of these patients was performed using the medical records
      and neuroimagings. RESULT: The ETV was performed safely and there were no
      intraoperative complications in all patients. The mean follow-up period was 12.3
      months. An immediate symptomatic relief of hydrocephalus and an adequate control
      of symptoms were achieved without a VP shunt in all patients. CONCLUSIONS: The
      ETV is considered to be an effective and safe procedure for the treatment of
      hydrocephalus in brainstem gliomas. Determining the ventriculostomy site
      according to the preoperative MRI in each case is considered to be important for
      the safe procedure.

PMID- 27041376
TI  - When Good Medications Go Bad, Don't DILI Dally.

PMID- 27041377
TI  - Lifestyle Interventions Including Nutrition, Exercise, and Supplements for
      Nonalcoholic Fatty Liver Disease in Children.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver
      disease among children. Lifestyle interventions, such as diet and exercise, are
      frequently recommended. Children with NAFLD have a distinct physiology that is
      different from obesity alone and has the potential to influence lifestyle
      treatments. Studies of diet alone in the treatment of pediatric NAFLD have
      focused on sugar and carbohydrate, but did not indicate any one dietary approach
      that was superior to another. For children who are obese and have NAFLD, weight
      loss may have a beneficial effect regardless of the diet used. Exercise is widely
      believed to improve NAFLD because a sedentary lifestyle, poor aerobic fitness,
      and low muscle mass are all risk factors for NAFLD. However, there have been no
      randomized controlled trials of exercise as a treatment for children with NAFLD.
      Studies of the combination of diet and exercise suggest a potential for
      improvement in serum alanine aminotransferase activity and/or magnetic resonance
      imaging liver fat fraction with intervention. There is also enthusiasm for the
      use of dietary supplements; however, studies in children have shown inconsistent
      effects of vitamin E, fish oil, and probiotics. This review presents the
      available data from studies of lifestyle intervention and dietary supplements
      published to date and highlights challenges that must be addressed in order to
      advance the evidence base for the treatment of pediatric NAFLD.

PMID- 27041378
TI  - Removable self-expanding metal stents insertion for the treatment of perforations
      and postoperative leaks of the esophagus.
AB  - BACKGROUND: Esophageal rupture, spontaneous or iatrogenic, is associated with
      significant morbidity and mortality. The current study aims at highlighting the
      various clinical scenarios, where esophageal fully covered self-expanding
      removable metal stents (FCSEMS) can be used in esophageal rupture. METHODS: In
      patients who underwent insertion of FCSEMS between January 2013 and June 2014,
      all data regarding demographics, indications, insertion, removal, and outcomes
      were studied retrospectively. RESULTS: Seven patients underwent the placement of
      esophageal covered SEMS. Two patients had Boerhaave syndrome, two had leak
      following the repair of aortic aneurysm, one had extensive esophageal injury
      following transesophageal echocardiography, one had carcinoma esophagus with
      tracheaesophageal fistula, and one had dehiscence of esophagogastric anastomosis.
      Stent insertion was successful in all the patients; one had stent migration which
      was managed endoscopically. Two patients died due to underlying illness; the rest
      had successful removal of stents after 8-10 weeks and good outcomes. CONCLUSION:
      Esophageal FCSEMS placement is safe and effective modality in management of
      patients with esophageal rupture.

PMID- 27041379
TI  - Percutaneous endoscopic management of intrahepatic stones in patients with
      altered biliary anatomy: A case series.
AB  - Incidence of primary intrahepatic stones (IHS) in India is very less as compared
      to the Far East. However patients with altered biliary anatomy are prone for IHS
      formation secondary to anastomotic stricture formation. Indian data on
      percutaneous endoscopic management of IHS is scare. Five patients with IHS were
      managed percutaneously. All patients had undergone Roux-en-Y hepaticojejunostomy
      and were not suitable for direct endoscopic intervention. All patients underwent
      percutaneous biliary drainage followed by cholangioscopy-guided laser
      lithotripsy. Crushed stones were pushed across the anastomotic site using
      basket/balloon and ductal clearance was achieved. Good stone pulverization could
      be achieved in five patients (100 %). Complete ductal clearance could be achieved
      in all patients (100 %). Cholangioscopy-guided treatment of IHS can be valuable
      alternative to surgery in select group of patients especially those having
      dilated biliary tree with absence of intrahepatic strictures. However long-term
      follow up studies are required to see for recurrence of stone formation. 

PMID- 27041380
TI  - Frequency, spectrum, and factors associated with fecal evacuation disorders among
      patients with chronic constipation referred to a tertiary care center in northern
      India.
AB  - BACKGROUND: Data on fecal evacuation disorder (FED) causing chronic constipation
      (CC) is scanty in India. METHODS: Prospectively maintained data of 249
      consecutive patients with CC (Rome III) referred for investigations were
      retrospectively analyzed. RESULTS: Of 249 patients (43.7 +/- 16.2 years, 174
      males), 135/242 (55.8 %), 57/249 (22.9 %), and 83/136 (61.0 %) had abnormal
      balloon expulsion test (>200 g), anorectal manometry [>100 mmHg resting pressure
      (n = 4), >167 mmHg squeeze pressure (n = 46), and both (n = 7)], and defecography
      (anorectal angle not opening by >15 degrees  during defecation, perineal descent
      >=4 cm, and/or rectocele), respectively. Though 181/249 (72.6 %) had one test
      abnormality, 86/249 (34 %) had FED (greater than or equal to two abnormalities),
      44/65 (67.6 %) of whom had a defecation index <=1.4. Rome III criteria for
      irritable bowel syndrome were equally fulfilled by patients with and without FED
      [74/83 (89 %) vs. 117/144 (81.2 %); p = ns]. On univariate analysis, straining
      duration, prolonged straining [>=30 min; 21/39 (53.8 %) vs. 15/65 (23.1 %); p =
      0.002], incomplete evacuation [75/77 (97.4 %) vs. 95/114 (83.3 %); p = 0.004],
      and >3 stools/week [60/75 (80 %) vs. 76/128 (60 %); p = 0.004] were commoner
      among the FED patients though age, gender, symptom duration, mucus, manual
      evacuation, and stool forms were comparable. Resting and squeeze pressures and
      balloon volume at maximum tolerable limit were higher, and the sphincter tended
      to be shorter in FED. Prolonged straining, incomplete evacuation, and squeeze
      pressure were significant on multivariate analysis. Manometry and defecography
      abnormalities were commoner among the female FED patients. CONCLUSION: FED is not
      uncommon, which fulfills the Rome III criteria for IBS, and prolonged straining
      may be suggestive; abnormal defecography and manometry are commoner in female.

PMID- 27041381
TI  - Knee pain during activities of daily living and its relationship with physical
      activity in patients with early and severe knee osteoarthritis.
AB  - This study aimed to investigate whether knee pain during various activities of
      daily living (ADLs) is associated with physical activity in patients with early
      and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs
      associated with decreased physical activity differ according to disease severity.
      This cross-sectional study enrolled 270 patients with medial knee OA, assigned to
      either the early (Kellgren Lawrence [K/L] grade 1-2) or the severe group (K/L
      grade 3-4). Physical activity was assessed using a pedometer. Knee pain during
      six ADLs (waking up in the morning, walking on a flat surface, ascending stairs,
      etc.) was evaluated using a questionnaire. We performed multiple regression and
      quantile regression analysis to investigate whether knee pain during each ADL was
      associated with physical activity. In the early group, the more knee pain they
      experienced while ascending stairs, the lower their physical activity was (75th
      regression coefficient = -1033.70, P = 0.018). In the severe group, the more knee
      pain they experienced while walking on a flat surface or bending to the floor or
      standing up, the lower their physical activity was (unstandardized coefficients =
      -1850.87, P = 0.026; unstandardized coefficients = -2640.35, P = 0.010). Knee
      pain while ascending stairs and while walking on a flat surface or bending to the
      floor or standing up was a probable limiting factor for physical activity in
      early and severe knee OA, respectively. These findings suggested that a reduction
      in task-specific knee pain according to disease severity could improve physical
      activity levels. 

PMID- 27041382
TI  - Predictors of remission, erosive disease and radiographic progression in a
      Colombian cohort of early onset rheumatoid arthritis: a 3-year follow-up study.
AB  - The objective of the study is to find predictors of remission, radiographic
      progression (RP), and erosive disease in a cohort of patients with early onset
      rheumatoid arthritis (EORA) that followed a therapeutic protocol aiming at
      remission, in a real world tight-control setting. EORA patients were enrolled in
      a 3-year follow-up study. Clinical, biological, immunogenetic, and radiographical
      data were analyzed. Radiographs were scored according to Sharp-van der Heijde
      (SvdH) method. RP was defined by an increase of 3 units in 36 months. Remission
      was defined as DAS28 <2.6. A stepwise multiple logistic regression model was used
      to identify independent predictors of the three target outcomes. One hundred
      twenty-nine patients were included. Baseline disease activity was high.
      Significant overall improvement was observed, but only 33.3 % achieved remission.
      At 36 month, 50.4 % (65) of patients showed erosions. RP was observed in 62.7 %
      (81) of cases. Statistical analysis showed that baseline SvdH score was the only
      predictive factor associated with the three outcomes evaluated. Lower HAQ-DI and
      absence of autoantibodies were predictive of remission. Higher levels of ESR and
      presence of erosions at entry were predictive of RP. Independent baseline
      predictors of incident erosive disease were anti-CCP and RF positivity, symptom
      duration at baseline >3 months, and presence of HLA-DRB1 shared epitope.
      Radiographic damage at baseline was the main predictor of outcomes.
      Autoantibodies, HAQ and ESR at baseline, symptom duration before diagnosis, and
      HLA-DRB1 status had influence on clinical course and development of structural
      joint damage in Colombian RA patients. 

PMID- 27041383
TI  - Signal transducer and activator of transcription 5 is implicated in disease
      activity in adult and juvenile onset systemic lupus erythematosus.
AB  - The Janus kinase/signal transducers and activators of transcription (JAK/STAT)
      pathway is one of a handful of pleiotropic cascades used to transduce a multitude
      of signals for development and homeostasis in humans. It is the principal
      signaling mechanism for a wide array of cytokines and growth factors.
      Dysregulated cytokine action on immune cells plays an important role in the
      initiation and progress of systemic lupus erythematosus (SLE). In this study, we
      tried to assess the role of STAT5 in systemic lupus erythematosus and correlate
      its phosphorylation level with the disease activity. The activation of the STAT5
      was assessed by measuring the level of expression of phosphorylated STAT5
      (pSTAT5) using flow cytometry on the peripheral blood T and B cells in 58 SLE
      patients (40 adult and 18 juvenile onset) and on 23 healthy age- and sex-matched
      controls for both groups. Serum prolactin level was also assessed in the patients
      and control by ELISA. The study revealed that the level of pSTAT5 was higher in
      adult SLE patients than in healthy control (p = 0.001) and in juvenile-onset SLE
      patients versus age-matched control (p = 0.031). A positive correlation existed
      between the pSTAT5 levels and Systemic Lupus Activity Measure (SLAM) score and
      also with multiple clinical manifestations indicating a potential role of STAT5
      signaling in pathogenesis SLE. The pSTAT5 signaling is implicated in the disease
      activity of SLE and may be a useful target of therapy by correcting the
      dysregulation of cytokines involved in the disease pathogenesis. 

PMID- 27041384
TI  - Causes of creatine kinase levels greater than 1000 IU/L in patients referred to
      rheumatology.
AB  - Patients with severely elevated creatine kinase (CK) concentrations are commonly
      referred to rheumatologists to evaluate for the presence of an idiopathic
      inflammatory myopathy (IIM). However, no studies have evaluated the frequency
      with which IIMs are encountered in this clinical scenario. The Vanderbilt
      Synthetic Derivative, a de-identified copy of over 2 million patient records, was
      searched to identify adult patients with a CK greater than 1000 IU/L who had been
      evaluated by a rheumatologist. Each patient was assigned a diagnosis using a pre
      determined algorithm. The records were then reviewed for pertinent demographic
      data and clinical characteristics. A total of 192 patients were included for
      analysis. Of these patients, 105 (55 %) were diagnosed with an IIM. The non-IIM
      causes were drug/toxin exposure (n = 16, 8 %), infection (n = 12, 6 %), trauma (n
      = 10, 5 %), myocardial injury (n = 5, 3 %), hypothyroidism (n = 4, 2 %), muscular
      dystrophy (n = 4, 2 %), neuropsychiatric disorder (n = 3, 2 %), metabolic
      myopathy (n = 2, 1 %), idiopathic CK elevation (n = 11, 6 %), and other diagnoses
      (n = 20, 10 %). Several characteristics were found to be significantly different
      between IIM and non-IIM cases. In particular, patients with an IIM were more
      likely to be female, have a positive ANA, have interstitial lung disease, and
      have proximal, symmetric weakness. This study found that approximately half of
      patients referred to our division of rheumatology with a CK greater than 1000
      IU/L were diagnosed with an IIM. Given the importance of prompt diagnosis and
      treatment of these disorders, rapid assessment by the consulting rheumatologist
      for these patients is recommended. 

PMID- 27041385
TI  - Utility of repeat head computed tomography after mild head trauma: influence on
      short- and long-term prognosis and health-related quality of life.
AB  - The aim of this study was to investigate the utility of repeat head CT in a large
      population of patients with non-isolated blunt mild head trauma (MTBI),
      especially in the presence of intracranial injury. This is a study of a cohort of
      478 non-isolated MTBI patients admitted to the High Dependency Unit of the
      Emergency Department of the University-Hospital of Florence from July 2008 to
      December 2013. Results of initial and subsequent head CT scans, and indications
      for repeat head CT scan (routine vs. neurologic change) were recorded. The study
      population was divided into two subgroups: 28 (6 %) patients with neurological
      change or persistently reduced GCS (group GCS-) and 450 (94 %) patients with
      normal or improving GCS (group GCS+). After 6 months from the event, a telephone
      interview using SF12 questionnaire was conducted. Among GCS- patients, the
      admission CT scan showed intracranial lesions (ICI) in 16 (57 %) patients; only
      two patients had a TBI-related neurosurgical intervention. Among GCS+ patients,
      the first CT scan showed an ICI in 133 patients; in a significant proportion of
      patients with ICI at the first CT scan, the injury worsened (40/133, 30 %, p <
      0.0001). However, no GCS+ patient had any neurosurgical intervention. We observed
      a significant reduction in both MCS and PCS scores after the injury compared with
      the previous period. The number of repeat CT scan was high in patients who
      presented ICI at the first CT scan; however, no patient with ICI and normal or
      improving GCS score needed a neurosurgical intervention.

PMID- 27041386
TI  - Massive gastric dilatation: the radiological picture of eating disorder.

PMID- 27041387
TI  - The known and missing links between Toxoplasma gondii and schizophrenia.
AB  - Toxoplasma gondii, an intracellular protozoan parasite, has a striking
      predilection for infecting the Central Nervous System and has been linked to an
      increased incidence of a number of psychiatric diseases. Several in vitro and in
      vivo studies have shown that T. gondii infection can affect the structure,
      bioenergetics and function of brain cells, and alters several host cell
      processes, including dopaminergic, tryptophan-kynurenine, GABAergic, AKT1,
      Jak/STAT, and vasopressinergic pathways. These mechanisms underlying the
      neuropathology of latent toxoplasmosis seem to operate also in schizophrenia,
      supporting the link between the two disorders. Better understanding of the
      intricate parasite-neuroglial communications holds the key to unlocking the
      mystery of T. gondii-mediated schizophrenia and offers substantial prospects for
      the development of disease-modifying therapies.

PMID- 27041388
TI  - Complex Camptosynpolydactyly and Mesoaxial synostotic syndactyly with phalangeal
      reduction are allelic disorders.
AB  - Complex Camptosynpolydactyly is an autosomal recessive disorder characterized by
      complex hand deformities described earlier by us in a consanguineous family. We
      report on identification of mutations in BHLHA9 gene in this condition. Our
      results indicate that Complex Camptosynpolydactyly and Mesoaxial synostotic
      syndactyly with phalangeal reduction (MSSD) are likely to be allelic disorders.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27041389
TI  - Healthcare costs and outcomes of managing beta-thalassemia major over 50 years in
      the United Kingdom.
AB  - BACKGROUND: The objective was to estimate the incidence-based costs of treating
      beta-thalassemia major (BTM) to the United Kingdom's National Health Service
      (NHS) over the first 50 years of a patient's life in terms of healthcare resource
      use and corresponding costs and the associated health outcomes. STUDY DESIGN AND
      METHODS: This was a modeling study based on information obtained from a
      systematic review of published literature and clinicians involved in managing BTM
      in the United Kingdom. A state transition model was constructed depicting the
      management of BTM over a period of 50 years. The model was used to estimate the
      incidence-based health economic impact that BTM imposes on the NHS and patients'
      health status in terms of the number of quality-adjusted life-years (QALYs) over
      50 years. RESULTS: The expected probability of survival at 50 years is 0.63. Of
      patients who survive, 33% are expected to be without any complication and the
      other 67% are expected to experience at least one complication. Patients' health
      status over this period was estimated to be a mean of 11.5 discounted QALYs per
      patient. Total healthcare expenditure attributable to managing BTM was estimated
      to be L483,454 ($720,201) at 2013/14 prices over 50 years. The cost of managing
      BTM could be potentially reduced by up to 37% if one in two patients had a bone
      marrow transplant, with an ensuing improvement in health-related quality of life.
      CONCLUSION: This analysis provides the best estimate available of NHS resource
      use and costs with which to inform policy and budgetary decisions pertaining to
      this rare disease.

PMID- 27041390
TI  - Tracing isolates from domestic human Campylobacter jejuni infections to chicken
      slaughter batches and swimming water using whole-genome multilocus sequence
      typing.
AB  - Campylobacter jejuni is the leading cause of bacterial gastroenteritis and
      chicken is considered a major reservoir and source of human campylobacteriosis.
      In this study, we investigated temporally related Finnish human (n=95), chicken
      (n=83) and swimming water (n=20) C. jejuni isolates collected during the seasonal
      peak in 2012 using multilocus sequence typing (MLST) and whole-genome MLST
      (wgMLST). Our objective was to trace domestic human C. jejuni infections to C.
      jejuni isolates from chicken slaughter batches and swimming water. At MLST level,
      79% of the sequence types (STs) of the human isolates overlapped with chicken STs
      suggesting chicken as an important reservoir. Four STs, the ST-45, ST-230, ST-267
      and ST-677, covered 75% of the human and 64% of the chicken isolates. In
      addition, 50% of the swimming water isolates comprised ST-45, ST-230 and ST-677.
      Further wgMLST analysis of the isolates within STs, accounting their temporal
      relationship, revealed that 22 of the human isolates (24%) were traceable back to
      C. jejuni positive chicken slaughter batches. None of the human isolates were
      traced back to swimming water, which was rather sporadically sampled. The highly
      discriminatory wgMLST, together with the patient background information and
      temporal relationship data with possible sources, offers a new, accurate approach
      to trace back the origin of domestic campylobacteriosis. Our results suggest that
      potentially a substantial proportion of campylobacteriosis cases during the
      seasonal peak most probably are due to other sources than chicken meat
      consumption. These findings warrant further wgMLST-based studies to reassess the
      role of other reservoirs in the Campylobacter epidemiology both in Finland and
      elsewhere. 

PMID- 27041391
TI  - Efficacy of cocoa pod extract as antiwrinkle gel on human skin surface.
AB  - OBJECTIVE: Cocoa pods are abundant waste materials of cocoa plantation, which are
      usually discarded onto plantation floors. However, due to poor plantation
      management, the discarded cocoa pods can create suitable breeding ground for
      Phytophthora palmivora, which is regarded as the causal agent of the black pod
      disease. On the other hand, cocoa pods potentially contain antioxidant compounds.
      Antioxidant compounds are related to the protection of skin from wrinkles and can
      be used as functional cosmetic ingredients. Therefore, in this study, cocoa pods
      were extracted and to be used as active ingredients for antiwrinkles. METHODS:
      The active compounds in cocoa pod extracts (CPE) were screened using liquid
      chromatography-mass spectrometry (LC-MS). Fibroblast cells were used to determine
      the effective concentration of CPE to maintain the viability for at least 50% of
      the cells (EC50 ). The gel was tested by 12 panelists to determine the efficacy
      of CPE in gel form using Visioscan to reduce skin wrinkles and improve skin
      condition. RESULTS: CPE was detected to contain malic acid, procyanidin B1,
      rosmarinic acid, procyanidin C1, apigenin, and ellagic acid, all of which may
      contribute to functional cosmetic properties of CPE. The EC50 value of cocoa pod
      extracts was used to calculate the amount of CPE to be incorporated into gel so
      that the formulated product could reach an effective concentration of extract
      while being nonintoxicant to the skin cell. The results showed that CPE is
      potential ingredient to reduce wrinkles. Skin wrinkles reduced at 6.38 +/- 1.23%
      with the application of the CPE gel within 3 weeks and significantly improved
      further (12.39 +/- 1.59%) after 5 weeks. The skin hydration increased (3.181 +/-
      1.06%) after 3 weeks of the CPE gel application. CONCLUSION: Flavonoid compounds
      in CPE contributed to the functional cosmetic properties of CPE. The CPE which is
      nontoxic to skin cells help to reduce wrinkles on skin after 3 weeks of
      application. CPE can be used as the active ingredients in antiwrinkle products,
      and prolonged application may result in significant visual changes to the naked
      eyes.

PMID- 27041392
TI  - Clg2p interacts with Clf and ClUrase to regulate appressorium formation,
      pathogenicity and conidial morphology in Curvularia lunata.
AB  - Ras is a small GTPase that regulates numerous processes in the cellular
      development and morphogenesis of many organisms. In this study, we identified and
      functionally characterized the Clg2p gene of Curvularia lunata, which is
      homologous with the Ras protein. The Clg2p deletion mutant (DeltaClg2p) had
      altered appressorium formation and conidial morphology and produced fewer,
      smaller lesions compared with the wild-type strain. When a dominant Clg2p allele
      was introduced into the mutant, all of these defective phenotypes were completely
      restored. To further understand the regulation of Clg2p in appressorium formation
      and conidial morphology, and its role in pathogenicity, seven Clg2p-interacting
      proteins were screened using a yeast two-hybrid assay. Two of these proteins,
      Clf, a homologue of Mst11, which corresponds to MAP kinase kinase kinase in
      Magnaporthe oryzae, and urate oxidase (designated ClUrase) were functionally
      characterized. Clg2p specifically interacted with Clf through its RA domain to
      regulate appressorium formation and pathogenicity, whereas the Clg2p-ClUrase
      interaction regulated conidial morphology without affecting fungal pathogenicity.
      This report is the first to elucidate the regulatory mechanism of the key Ras
      protein Clg2p in C. lunata. 

PMID- 27041393
TI  - Inhalation TTC values: A new integrative grouping approach considering
      structural, toxicological and mechanistic features.
AB  - The present publication describes an integrative grouping concept to derive
      threshold values for inhalation exposure. The classification scheme starts with
      differences in toxicological potency and develops criteria to group compounds
      into two potency classes, namely toxic (T-group) or low toxic (L-group). The TTC
      concept for inhalation exposure is based on the TTC RepDose data set, consisting
      of 296 organic compounds with 608 repeated-dose inhalation studies. Initially, 21
      structural features (SFs) were identified as being characteristic for compounds
      of either high or low NOEC values (Schuurmann et al., 2016). In subsequent
      analyses these SF groups were further refined by taking into account structural
      homogeneity, type of toxicological effect observed, differences in absorption,
      metabolism and mechanism of action (MoA), to better define their structural and
      toxicological boundaries. Differentiation of a local or systemic mode of action
      did not improve the classification scheme. Finally, 28 groups were discriminated:
      19 T-groups and 9 L-groups. Clearly distinct thresholds were derived for the T-
      and L-toxicity groups, being 2 * 10(-5) ppm (2 MUg/person/day) and 0.05 ppm (4260
      MUg/person/day), respectively. The derived thresholds and the classification are
      compared to the initial mainly structure driven grouping (Schuurmann et al.,
      2016) and to the Cramer classification. 

PMID- 27041394
TI  - Best-practices approach to determination of blood alcohol concentration (BAC) at
      specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling
      and post-mortem alcohol generation and transport considerations.
AB  - Alcohol concentrations in biological matrices offer information regarding an
      individual's intoxication level at a given time. In forensic cases, the alcohol
      concentration in the blood (BAC) at the time of death is sometimes used
      interchangeably with the BAC measured post-mortem, without consideration for
      alcohol concentration changes in the body after death. However, post-mortem
      factors must be taken into account for accurate forensic determination of BAC
      prior to death to avoid incorrect conclusions. The main objective of this work
      was to describe best practices for relating ante-mortem and post-mortem alcohol
      concentrations, using a combination of modeling, empirical data and other
      qualitative considerations. The Widmark modeling approach is a best practices
      method for superimposing multiple alcohol doses ingested at various times with
      alcohol elimination rate adjustments based on individual body factors. We
      combined the selected ante-mortem model with a suggestion for an approach used to
      roughly estimate changes in BAC post-mortem, and then analyzed the available data
      on post-mortem alcohol production in human bodies and potential markers for
      alcohol production through decomposition and putrefaction. Hypothetical cases
      provide best practice approaches as an example for determining alcohol
      concentration in biological matrices ante-mortem, as well as potential issues
      encountered with quantitative post-mortem approaches. This study provides
      information for standardizing BAC determination in forensic toxicology, while
      minimizing real world case uncertainties. 

PMID- 27041395
TI  - Physicians prefer greater detail in the biosimilar label (SmPC) - Results of a
      survey across seven European countries.
AB  - In the European Union, labels (Summaries of Product Characteristics, SmPCs) of
      biosimilars and their reference products are in many instances almost identical
      (following a generic approach) despite different data requirements for the
      authorization of biosimilars and generics. To understand physicians' preferences
      on type and detail of information in the biosimilar label and their use of
      information sources when prescribing biologics including biosimilars, EuropaBio
      surveyed 210 physicians across seven European countries. Among surveyed
      physicians, 90.5% use the label frequently or occasionally as an information
      source and 87.2% deemed a clear statement on the origin of data helpful or very
      helpful. When comparing excerpts from the label of an authorized biosimilar and
      modified texts with additional information, 78.1-82.9% preferred the samples with
      additional information. This survey shows that the label is an appropriate
      vehicle for providing physicians with information about biologics and that
      physicians prefer more product-specific information in the biosimilar label. 

PMID- 27041396
TI  - Development of a 3'-amino linker with high conjugation activity and its
      application to conveniently cross-link blunt ends of a duplex.
AB  - The 2-aminoethyl carbamate linker (ssH linker) exhibits high activity in
      modifying the 5'-termini of oligonucleotides; however, the ssH linker is not
      appropriate for 3'-terminal modification because it undergoes intramolecular
      trans-acylation under heat-aqueous ammonia conditions. We developed an N-(2
      aminoethyl)carbamate linker (revH linker), in which the carbamate is oriented in
      the reverse direction relative to that in 2-aminoethyl carbamate. The revH linker
      was tolerant to heat-alkaline conditions and retained its high reactivity in
      conjugation with exogenous molecules. The 3'-revH linker was efficiently linked
      with the 5'-ssH linker at the termini of complementary double strands with a
      bifunctional molecule, producing a synthetic loop structure. An anti-microRNA
      oligonucleotide (AMO) was prepared from the chemical ligation of three-stranded
      2'-O-methyl RNAs, and the AMO with two alkyl loops exhibited high inhibition
      activity toward miRNA function. The revH linker is not only useful for 3'
      terminal modification of oligonucleotides but also expands the utility range in
      combination with the 5'-ssH linker. 

PMID- 27041397
TI  - Design, synthesis, and biological evaluation of arylpiperazine-benzylpiperidines
      with dual serotonin and norepinephrine reuptake inhibitory activities.
AB  - The limitations of established serotonin (5-hydroxytryptamine, 5-HT) and
      norepinephrine (NE) reuptake inhibitors necessitate the development of safer and
      more effective therapeutic agents. Based on the structures of 4-benzylpiperidine
      carboxamides and trazodone, arylpiperazine-benzylpiperidines with chemical
      scaffolds different from those of marketed drugs were designed, synthesized, and
      evaluated for their neurotransmitter reuptake inhibitory activities. The majority
      of the synthesized compounds showed greater NE than 5-HT reuptake inhibition. The
      activities were even greater than those of the standard drug, venlafaxine
      hydrochloride were. The derivatives with a three-carbon linker showed better
      activities than the derivatives with a two-carbon linker. Among the newly
      synthesized compounds, 2d exhibited the strongest reuptake inhibition of the
      neurotransmitters (IC50=0.38 MUM for NE and 1.18 MUM for 5-HT). The biological
      activity data demonstrate that arylpiperazine-benzylpiperidines have the
      potential to be developed as a new class of therapeutic agents to treat
      neuropsychiatric and neurodegenerative disorders.

PMID- 27041398
TI  - Synthesis and antitumor activity evaluation of a novel combi-nitrosourea prodrug:
      Designed to release a DNA cross-linking agent and an inhibitor of O(6)
      alkylguanine-DNA alkyltransferase.
AB  - The drug resistance of CENUs induced by O(6)-alkylguanine-DNA alkyltransferase
      (AGT), which repairs the O(6)-alkylated guanine and subsequently inhibits the
      formation of dG-dC cross-links, hinders the application of CENU chemotherapies.
      Therefore, the discovery of CENU analogs with AGT inhibiting activity is a
      promising approach leading to novel CENU chemotherapies with high therapeutic
      index. In this study, a new combi-nitrosourea prodrug 3-(3-(((2-amino-9H-purin-6
      yl)oxy)methyl)benzyl)-1-(2-chloroethyl)-1-nitrosourea (6), designed to release a
      DNA cross-linking agent and an inhibitor of AGT, was synthesized and evaluated
      for its antitumor activity and ability to induce DNA interstrand cross-links
      (ICLs). The results indicated that 6 exhibited higher cytotoxicity against mer(+)
      glioma cells compared with ACNU, BCNU, and their respective combinations with
      O(6)-benzylguanine (O(6)-BG). Quantifications of dG-dC cross-links induced by 6
      were performed using HPLC-ESI-MS/MS. Higher levels of dG-dC cross-link were
      observed in 6-treated human glioma SF763 cells (mer(+)), whereas lower levels of
      dG-dC cross-link were observed in 6-treated calf thymus DNA, when compared with
      the groups treated with BCNU and ACNU. The results suggested that the superiority
      of 6 might result from the AGT inhibitory moiety, which specifically functions in
      cells with AGT activity. Molecular docking studies indicated that five hydrogen
      bonds were formed between the O(6)-BG analogs released from 6 and the five
      residues in the active pocket of AGT, which provided a reasonable explanation for
      the higher AGT-inhibitory activity of 6 than O(6)-BG. 

PMID- 27041399
TI  - Design, synthesis, and evaluation of hinge-binder tethered 1,2,3
      triazolylsalicylamide derivatives as Aurora kinase inhibitors.
AB  - A series of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives were
      designed, synthesized, and evaluated for the Aurora kinase inhibitory activities.
      The novel hinge-binder tethered 1,2,3-triazolylsalicylamide scaffold was
      effectively assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition
      (CuAAC). A variety of alkynes with hinge binders were used to search proper
      structures-binding relationship to the hinge region. The synthesized 1,2,3
      triazolylsalicylamide derivatives showed significant Aurora kinase inhibitory
      activity. In particular, 8a inhibited Aurora A kinase with an IC50 value of 0.284
      MUM, whereas 8m inhibited Aurora B kinase with an IC50 value of 0.364 MUM.

PMID- 27041400
TI  - Cantharis by photosynthetic bacteria biotransformation: Reduced toxicity and
      improved antitumor efficacy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The blister beetle, also known as Mylabris
      cichorii, is not only widely used in clinical applications in Chinese anticancer
      medicine, but is also one of the main ingredients in a variety of traditional
      Chinese medicinal preparations with anticancer activity. However, the strong
      toxicity exhibited by this beetle species limits its clinical applicability, with
      the photosynthetic bacteria featuring a strong biological conversion function.
      Therefore, in this study we explore the use of photosynthetic bacteria for
      bioconversion of the blister beetle in order to reduce the toxicity and in effort
      to enhance the overall antitumor effect. METHODS AND RESULTS: In the first set of
      experiments, we utilized an orthogonal experimental design to optimize the
      culture medium of photosynthetic bacteria. Concurrently, the growth curve of
      photosynthetic bacteria was used to determine the inoculation amount of the
      photosynthetic bacteria and the safe concentration of cantharis. Through
      antitumor activity experiments conducted in vitro we found that the inhibition
      rate increased through cantharis by PSB biotransformation of HepG2, A549 and BEL
      7406 cells. Furthermore, through acute toxicity tests in mice it was found that
      the blister beetle water extraction liquid exhibits a LD50 value of 1383mg/kg,
      while the blister beetle transformation liquid exhibits a LD50 value of 206mg/kg.
      The LD50 value of the blister beetle water extract was found to be 6.7 times
      higher than the transformation liquid, thus demonstrating that the toxicity of
      cantharis by PSB biotransformation may be decreased. More strikingly, decreased
      toxicity was observed in the mouse liver and in pathological sections of the
      kidneys after transformation. CONCLUSIONS: In this paper we demonstrate for the
      first time that PSB bioconversion of the blister beetle is able to reduce the
      toxicity of a common method used in anticancer treatments as part of the
      principles in traditional Chinese medicine and may therefore improve antitumor
      activity in vitro.

PMID- 27041401
TI  - Screening for potential alpha-glucosidase and alpha-amylase inhibitory
      constituents from selected Vietnamese plants used to treat type 2 diabetes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The 18 plant species investigated in this study
      have been used as herbal antidiabetic remedies in Vietnamese traditional
      medicines. This study aimed to evaluate their ability to inhibit alpha
      glucosidase and alpha-amylase, two key enzymes involved in serum glucose
      regulation. MATERIALS AND METHODS: Chloroform, ethanol and water extracts of 18
      plants were screened for alpha-glucosidase and alpha-amylase inhibitory activity.
      Analytical-scale HPLC was subsequently used to investigate the most active
      extracts, where samples with low level of tannins were identified and
      fractionated into 96-well microplates, followed by alpha-glucosidase and alpha
      amylase assessment of each well. High-resolution alpha-glucosidase and alpha
      amylase inhibition profiles constructed from these assays allowed identification
      of HPLC peaks correlated with alpha-glucosidase and alpha-amylase inhibitory
      activity. The active constituents were subsequently isolated using preparative
      scale HPLC and their structure was elucidated by HR-ESIMS and NMR. RESULTS:
      Ethanol extracts of Nepenthes mirabilis, Phyllanthus urinaria, and Kandelia
      candel significantly inhibited alpha-glucosidase with IC50 values of 32.7+/-6.3,
      39.7+/-9.7, and 35.4+/-13.9MUg/mL, respectively. Water extracts of N. mirabilis,
      Phyllanthus amarus, P. urinaria, Lagerstroemia speciosa, Syzygium cumini,
      Rhizophora mucronata, and K. candel showed IC50 values of 3.3+/-0.8, 34.9+/-1.5,
      14.6+/-4.6, 5.4+/-0.5, 20.9+/-1.8, 3.3+/-0.6, and 4.0+/-0.8MUg/mL, respectively.
      In the alpha-amylase inhibition assay, ethanol extracts of K. candel and Ficus
      racemosa showed IC50 of 7.6+/-0.9 and 46.7+/-23.6MUg/mL, respectively. Showing
      low tannin constituents as seen from HPLC profiles, P. amarus and P. urinaria
      water extracts and F. racemosa ethanol extract were subjected to
      microfractionation. Only high-resolution alpha-glucosidase inhibition profiles of
      P. amarus and P. urinaria water extracts showed several active compounds, which
      were isolated and identified as corilagin (1), repandusinic acid A (2), and
      mallotinin (3). IC50 of these compounds were 1.70+/-0.03, 6.10+/-0.10, and 3.76+/
      0.15MUM, respectively. Kinetics analysis revealed that 1 displayed a mixed type
      mode of inhibition with Ki and Ki' values of 2.37+/-0.90 and 2.61+/-0.61MUM,
      respectively, whereas 2 and 3 competitively inhibited alpha-glucosidase with Ki
      values of 4.01+/-0.47 and 0.65+/-0.11MUM, respectively. CONCLUSION: Corilagin
      (1), repandusinic acid A (2), and mallotinin (3) were potent alpha-glucosidase
      inhibitors contributing significantly to the inhibitory effect observed for the
      water extracts of P. amarus and P. urinaria.

PMID- 27041402
TI  - Zanthoxylum bungeanum essential oil induces apoptosis of HaCaT human
      keratinocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum bungeanum (ZB), a Chinese herb
      medicine, has been shown to possess a wide range of biological activities
      including anti-tumor, anti-inflammatory, and anti-microbial activity and has long
      been used to treat a variety of skin diseases including psoriasis. However, the
      underlying mechanism of action has not been systematically elucidated. AIM OF THE
      STUDY: to analyze the chemical composition of the hydro-distilled Zanthoxylum
      bungeanum essential oil (ZBEO), and to investigate its anti-proliferative
      activity on HaCaT cells as well as the underlying anti-psoriasis mechanisms.
      MATERIALS AND METHODS: The chemical composition of ZBEO was analyzed with gas
      chromatography coupled to mass spectrometry (GC-MS). HaCaT cells was exposed to
      different dose of ZBEO added in medium prior to morphologic features analysis as
      well as cell cycle arrest examination with Flow cytometry. Western blot analysis
      was employed to estimate the expression level of proteins including caspase
      8/9/3, PARP, Bax and Bcl-2. RESULTS: Thirty-nine compounds of the ZBEO were
      identified GC-MS. ZBEO-treated HaCaT cells showed typical apoptotic morphologic
      features by DAPI staining assay. The ZBEO significantly inhibited proliferation
      of HaCaT cells in a dose- and time-dependent manner and induced S phase arrest
      apoptosis in HaCaT cells. Furthermore, western blot analysis revealed that the
      ZBEO increased expression of cleaved caspase-8/9/3, PARP, and Bax, decreased Bcl
      2 levels. CONCLUSION: ZBEO inhibits the proliferation of HaCaT cells, resulting
      from the induction of cellular apoptosis through both intrinsic and extrinsic
      pathways. ZBEO is a potential candidate that may be considered for development
      into an anti-psoriasis drug.

PMID- 27041403
TI  - (1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive
      extract on ischemic stroke rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Stroke is a leading cause of death and disability
      in the world. However, current therapies are limited. Naodesheng, a widely used
      traditional Chinese medicine prescription, has shown a good clinical curative
      effect on ischemic stroke. Also, Naodesheng has been suggested to have
      neuroprotective effect on focal cerebral ischemia rats, but the underlying
      molecular mechanism remains unclear. AIM OF THE STUDY: The present study was
      designed to evaluate the effect of Naodesheng bioactive extract on the metabolic
      changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion
      injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based
      metabonomics approach. MATERIALS AND METHODS: A middle cerebral artery occlusion
      rat model was established and confirmed by the experiments of neurobehavioral
      abnormality evaluation, brain tissue TTC staining and pathological examination.
      The metabolic changes in brain tissue, plasma and urine were then assessed by a
      (1)H NMR technique combined with multivariate statistical analysis method.
      RESULTS: These NMR data showed that cerebral ischemia reperfusion induced great
      metabolic disorders in brain tissue, plasma and urine metabolisms. However,
      Naodesheng bioactive extract could reverse most of the imbalanced metabolites.
      Meanwhile, it was found that both the medium and high dosages of Naodesheng
      bioactive extract were more effective on the metabolic changes than the low
      dosage, consistent with histopathological assessments. CONCLUSIONS: These results
      revealed that Naodesheng had protective effect on ischemic stroke rats and the
      underlying mechanisms involved multiple metabolic pathways, including energy
      metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The
      present study could provide evidence that metabonomics revealed its capacity to
      evaluate the holistic efficacy of traditional Chinese medicine and explore the
      underlying mechanisms.

PMID- 27041404
TI  - Pitavastatin versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol
      in Patients with Dyslipidemias.
AB  - Remnant lipoproteins cholesterol are products of partially catabolized
      chylomicrons and very-low-density lipoprotein, from which some triglycerides have
      been removed. These particles are smaller and are believed to be strongly
      atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be
      associated with endothelial dysfunction and atherosclerotic disease.

PMID- 27041405
TI  - Comments on Watson, the Microbiome of Children, and Patient-reported Outcomes.

PMID- 27041406
TI  - Patient-reported Symptom Experiences in Patients With Carcinoid Syndrome After
      Participation in a Study of Telotristat Etiprate: A Qualitative Interview
      Approach.
AB  - PURPOSE: Telotristat etiprate, a tryptophan hydroxylase inhibitor, was previously
      evaluated in a Phase II randomized, placebo-controlled clinical trial in patients
      with carcinoid syndrome (CS) and diarrhea not adequately controlled by
      octreotide. The objective of the current study was to characterize the symptom
      experiences of patients participating in that trial. METHODS: Consenting patients
      participated in one-on-one, qualitative interviews focused on eliciting symptoms
      they had experienced in association with their CS diagnosis and recollection of
      symptom changes they experienced while participating in the Phase II trial.
      FINDINGS: Among the 23 patients who participated in the previous 4-week dose
      escalation study, 16 were eligible for interviews and 11 participated in the
      present study. The median time from study completion to the interview was 31
      months; 4 of 11 patients were receiving telotristat etiprate in a follow-up, open
      label trial at the time of interview. All of the patients (100%) described
      diarrhea as a symptom of CS, with effects on the emotional, social, and physical
      aspects of their lives. Improvement in diarrhea during the study was described by
      82% of participants, and was very impactful in several patients. Results led to
      the design and implementation of a larger interview program in Phase III and
      helped to establish a definition of clinically meaningful change for the clinical
      development program. IMPLICATIONS: The diarrhea associated with CS can have a
      large impact on daily lives, and patient interviews can characterize and capture
      clinically meaningful improvements with treatment. ClinicalTrials.gov Identifier:
      NCT00853047.

PMID- 27041407
TI  - Using Patient-reported Outcomes to Compare Relative Burden of Cancer: EQ-5D and
      Functional Assessment of Cancer Therapy-General in Eleven Types of Cancer.
AB  - PURPOSE: The objective of this study was to compare the health-related quality of
      life (HRQL) burden across different types of advanced cancer with the use of 2
      widely used patient-reported outcome measures, the generic EQ-5D and the cancer
      specific Functional Assessment of Cancer Therapy-General (FACT-G). METHODS:
      Patients with advanced cancer of the bladder, brain, breast, colon/rectum,
      head/neck, hepatobiliary tract/pancreas, kidney, lung, lymphoma, ovary, or
      prostate completed the EQ-5D and FACT-G. HRQL domains and summary scores were
      compared across types of cancer, using regression models to adjust for age and
      sex. FINDINGS: Approximately 50 patients with each type of cancer were recruited
      (total, 534 patients). According to EQ-5D dimensions, the highest proportion of
      problems was associated with prostate (mobility); prostate and kidney (self
      care); head/neck, bladder, and lung (usual activities); breast, head/neck, and
      lung (pain/discomfort); and lymphoma and lung (anxiety/depression) cancers. EQ-5D
      visual analogue scale scores were lowest for breast and head/neck cancers; US
      index-based scores were lowest for breast and lung cancers and highest for brain
      cancer. For the FACT-G, physical well-being scores were lowest for head/neck,
      hepatobiliary, and kidney cancers; emotional well-being scores were lowest for
      hepatobiliary cancer, and functional well-being scores were lowest for head/neck,
      hepatobiliary, and bladder cancers. IMPLICATIONS: The overall and dimension
      specific HRQL burden of advanced cancer depended on the type of cancer. Such
      results may aid clinicians and patients in better understanding of how cancer
      site can affect HRQL and functioning in different ways.

PMID- 27041408
TI  - Qualitative Development and Content Validity of the Non-small Cell Lung Cancer
      Symptom Assessment Questionnaire (NSCLC-SAQ), A Patient-reported Outcome
      Instrument.
AB  - PURPOSE: The purpose of this article was to describe the process and results of
      the preliminary qualitative development of a new symptoms-based patient-reported
      outcome (PRO) measure intended for assessing treatment benefit in clinical trials
      of advanced non-small cell lung cancer (NSCLC). METHODS: Individual qualitative
      interviews were conducted in adults with NSCLC (Stages I-IV) in the United
      States. Experienced interviewers conducted concept-elicitation (CE) and cognitive
      interviews using semistructured interview guides. The CE interview guide was used
      for eliciting spontaneous reports of symptom experiences along with probing to
      further explore and confirm concepts. Interview transcripts were coded and
      analyzed by professional qualitative coders, and were summarized by like content
      using an iterative coding framework. Data from the CE interviews were considered
      alongside existing literature and clinical expert opinion during an item
      generation process, leading to the development of a preliminary version of the
      NSCLC Symptom Assessment Questionnaire (SAQ). Three waves of cognitive interviews
      were conducted to evaluate concept relevance, item interpretability, and
      structure of the draft items and to facilitate further instrument refinement.
      FINDINGS: Fifty-one subjects (mean [SD] age, 64.9 [11.2] years; 51.0% women)
      participated in the CE interviews. A total of 1897 expressions of NSCLC-related
      symptoms were identified and coded in interview transcripts, representing ~42
      distinct symptom concepts. A 9-item initial-draft instrument was developed for
      testing in 3 waves of cognitive interviews with additional subjects with NSCLC (n
      = 20), during which both paper and electronic versions of the instrument were
      evaluated and refined. Participant responses and feedback during cognitive
      interviews led to the removal of 2 items and substantial modifications to others.
      IMPLICATIONS: The NSCLC-SAQ is a 7-item PRO measure intended for use in advanced
      NSCLC clinical trials to support medical product labelling. The NSCLC-SAQ uses a
      7-day recall period and verbal rating scales. It was developed in accordance with
      the US Food and Drug Administration's PRO Guidance and scientific best practices,
      and the resulting qualitative interview data provide evidence of content
      validity. The NSCLC-SAQ has been prepared in both paper and electronic
      administration formats and a tablet computer-based version is currently
      undergoing quantitative testing to confirm its measurement properties and support
      US Food and Drug Administration qualification.

PMID- 27041409
TI  - Patient-reported Symptoms of Tenosynovial Giant Cell Tumors.
AB  - PURPOSE: Tenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm
      of the synovium of joints and tendon sheaths, is associated with joint
      destruction, inflammation, pain, and swelling, in part due to colony-stimulating
      factor 1 receptor-bearing macrophages recruited to the tumor by genetic elevation
      of colony-stimulating factor 1 activity. The most common treatment is surgery,
      although promising pharmacologic treatments are in development. Patient-reported
      outcome (PRO) instruments are critical end points in demonstrating the clinical
      relevance of standard oncologic outcome measures and the overall impact of novel
      pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The
      content validity of PROs relevant to patients with TGCT has not been formally
      investigated, and instruments to evaluate such outcomes do not exist for this
      condition. METHODS: PRO instruments of potential relevance were evaluated by
      using a literature review and by clinical and PRO experts. Patients with TGCT
      were recruited through clinical sites and the Internet for participation in
      qualitative research interviews to identify predominant symptoms and to test the
      relevance and content validity of several PRO measures. Select PRO measures were
      included in a Phase I clinical trial, and preliminary results of the PRO end
      points are reported descriptively. FINDINGS: Of the 22 subjects who participated
      in qualitative interviews, 73% were female, and their mean age was 42.5 years
      (range, 27-56 years). The TGCTs (19 diffuse and 3 localized) were located in the
      knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n = 1), and forearm (n = 1).
      The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%),
      reduced range of motion (64%), and joint instability (64%), which were consistent
      with clinical expert input and with the content of instruments chosen by PRO
      experts. The worst pain numeric rating scale, Patient Reported Outcomes
      Measurement Information System physical functioning items, and the Western
      Ontario and McMaster Universities Osteoarthritis Index, as well as a worst
      stiffness numeric rating scale developed for TGCT, were confirmed as meaningful
      measures of TGCT patient symptoms and were well understood in qualitative
      interviews. Results from the Phase I trial showed trends of improvement in both
      pain and stiffness over time. IMPLICATIONS: This study is the first to gather
      information directly from patients with TGCT regarding their symptom experiences.
      Pain, stiffness, and physical functioning are important treatment outcomes in
      patients with TGCT. We have identified content-valid PRO measures of these
      concepts, which are included in an ongoing Phase III TGCT clinical trial with
      pexidartinib (PLX3397) (NCT02371369).

PMID- 27041410
TI  - Progress Report on Neglected Tropical Disease Drug Donation Programs.
AB  - PURPOSE: Neglected tropical diseases (NTDs) impose a significant burden on public
      health, particularly in developing nations. Many can be treated cost-effectively
      with drugs donated or offered at or below marginal cost. In 2012, the World
      Health Organization published an NTD roadmap that outlined a strategy for the
      prevention, control, and eradication of 17 NTDs by 2020. Inspired by this
      roadmap, executives from 13 pharmaceutical companies, government agencies, and
      other interested parties signed the London Declaration on Neglected Tropical
      Diseases in January 2012. In this paper, we will assess progress in meeting
      commitments on drug donations laid out in the London Declaration. METHODS: We
      conducted Medline and LexisNexis searches of peer-reviewed publications and trade
      journals, as well as product development partnership and government reports.
      Subsequently, we designed a survey instrument and surveyed 10 company signatories
      (companies with drug donation programs) to the London Declaration to determine
      current donations and pledges. FINDINGS: Nine of 10 companies with donation
      programs responded to the survey. The respondents reported substantial progress
      in meeting the goals laid out in the London Declaration. Survey respondents
      maintained 17 drug donation programs across 10 disease categories. In 2014,
      companies donated >1 billion treatments, with a dollar value of nearly $1.5
      billion. However, not all donated products were distributed to patients in need.
      In addition, 4 of the 17 programs were slated to end before 2020, three of the 17
      programs did not report explicit program objectives, and 7 of 17 did not measure
      the impact of programs in terms of numbers of patients treated. None of our
      survey respondents reported on whether the programs were leading to a reduction
      in disease prevalence. IMPLICATIONS: Donations are a necessary but insufficient
      condition for patient access to neglected disease drugs. Additional resources
      must be allocated to ensure delivery of donated products to patients. In
      addition, drug donation programs should provide explicit descriptions of program
      objectives, measurements of the impacts of their programs, and extension of all
      donation commitments through 2020. To achieve this, multiple stakeholders with a
      vested interest in reducing the burden of neglected diseases must collaborate in
      a multipronged approach toward NTD elimination.

PMID- 27041411
TI  - Genetic Testing in Pancreatic Ductal Adenocarcinoma: Implications for Prevention
      and Treatment.
AB  - PURPOSE: This article reviews the progress to date and future directions for
      investigation of germline and somatic genetic testing to inform pancreatic
      adenocarcinoma (PDAC) treatment, screening, and prevention strategies. METHODS:
      We searched PubMed to identify recent articles regarding genetic testing in
      pancreatic cancer, including both germline and somatic testing, and recent genome
      wide association studies. References were specifically hand searched as relevant.
      Guidelines for testing and screening high-risk individuals were included. We
      searched clinicaltrials.gov to review the current landscape of active clinical
      trials. FINDINGS: Approximately 10% of PDACs are associated with an identified
      germline mutation. Although germline mutations may inform treatment options and
      identify high-risk individuals for screening in other cancers, the data on PDAC
      are only now emerging. For example, poly adenosine diphosphate ribose polymerase
      (PARP) inhibitors are under investigation for BRCA-associated PDAC. Somatic
      mutations have also been identified in PDAC. However, current data are limited
      regarding treatment for potential PDAC somatic driver mutations. Although
      erlotinib is used in PDAC, its use is not targeted based on a tumor marker. Many
      tyrosine kinase inhibitors targeted toward potential driver mutations and
      critical pathways are in development, including BRAF/MEK, ALK, and CDK4/6. A
      consensus on screening strategies for individuals at high risk for PDAC is still
      evolving because of the relatively low prevalence of the disease, the relative
      invasiveness of endoscopic procedures often used as part of screening, and the
      lack of a clear survival benefit. IMPLICATIONS: Pancreatic cancer has been slower
      to move toward genomic testing, partially because of a lower prevalence of
      mutations and partially because of a limited effect of results on treatment
      choices outside a clinical trial. This is an area of active investigation, and we
      anticipate that there will be both preventive and therapeutic implications of
      driver mutations in the coming decade.

PMID- 27041412
TI  - Genomic Alterations and Targeted Therapy in Gastric and Esophageal
      Adenocarcinoma.
AB  - PURPOSE: Gastric and esophageal adenocarcinomas are common and aggressive
      malignancies. Systemic therapy for these tumors is based primarily on cytotoxic
      chemotherapy, but outcomes remain poor. Precision medicine, where treatments are
      tailored to specific molecular abnormalities of tumors, holds great promise for
      improving outcomes in this disease. METHODS: A search was performed in PubMed to
      identify studies that have characterized the molecular basis of gastric and
      esophageal adenocarcinoma, as well as clinical trials exploring targeted
      therapies in this disease. FINDINGS: Recent genomic studies have identified
      potentially targetable genomic alterations in gastroesophageal adenocarcinoma.
      Specifically, The Cancer Genome Atlas study defined 4 subgroups of gastric
      cancer, each harboring distinct genomic features. However, development of
      targeted therapies for gastroesophageal cancer has been challenging. The only
      biomarker-driven therapy in clinical practice, trastuzumab for the ~15% of
      patients with human epidermal growth factor receptor 2-positive disease, is
      modestly effective, extending median overall survival by 2.7 months. Clinical
      trials of other targeted therapies, including epidermal growth factor receptor,
      fibroblast growth factor receptor 2, and MET inhibitors, have had disappointing
      results so far. IMPLICATIONS: The availability of genomic tools provides an
      unprecedented opportunity to develop new rational therapeutic strategies. New
      trial designs of targeted therapies in biomarker-selected patient populations
      have the potential to improve outcomes in this lethal disease. As these clinical
      trials are being developed, it is increasingly important to incorporate
      correlative studies that will allow us to identify biomarkers of response or
      resistance to targeted therapies.

PMID- 27041413
TI  - Self-Assembled Thermoresponsive Nanogels Prepared by Reverse Micelle -> Positive
      Micelle Method for Ophthalmic Delivery of Muscone, a Poorly Water-Soluble Drug.
AB  - This study aimed to design a nanocarrier ophthalmic delivery system of muscone, a
      poorly water-soluble drug. The muscone thermoresponsive nanogels were self
      assembled by reverse micelle -> positive micelle method. Muscone was demonstrated
      to have uniform narrow particle size distribution in nanogel by the dynamic light
      scattering test. The developed nanocomposite hydrogel had a high muscone loading,
      and the rheology results showed that the phase transition temperature was 34.05
      degrees C. Thixotropy test indicated that the nanogel was able to resist the
      blinking of eyes because of the thixotropy recovery time, which is <5 s. Compared
      with muscone eye drops, muscone nanogels showed longer retention time on the
      corneal surface using fluorescent labeling technology and produced a 3.4-fold
      increase in apparent permeability coefficients (Papp). Draize testing showed that
      the developed nanogel caused no eye irritation. In vivo pharmacokinetic study
      indicated that the nanogel could significantly increase the bioavailability of
      muscone after administration compared with eye drops. These results indicate that
      self-assembled thermoresponsive nanogel prepared by reverse micelle -> positive
      micelle method has potential for the ophthalmic delivery of poorly water-soluble
      drugs.

PMID- 27041414
TI  - IMAGING OF OXYGEN DYNAMICS WITHIN THE ENDOLITHIC ALGAL COMMUNITY OF THE MASSIVE
      CORAL PORITES LOBATA(1).
AB  - We used transparent planar oxygen optodes and a luminescence lifetime imaging
      system to map (at a pixel resolution of <200 MUm) the two-dimensional
      distribution of O2 within the skeleton of a Porites lobata colony. The O2
      distribution was closely correlated to the distribution of the predominant
      endolithic microalga, Ostreobium quekettii Bornet et Flahault that formed a
      distinct green band inside the skeleton. Oxygen production followed the outline
      of the Ostreobium band, and photosynthetic O2 production was detected at only 0.2
      MUmol photons m(-2)  . s(-1) , while saturation occurred at ~37 MUmol photons m(
      2)  . s(-1) . Oxygen levels varied from ~60% to 0% air saturation in the
      illuminated section of the coral skeleton in comparison to the darkened section.
      The O2 production within the Ostreobium band was lower in the region below the
      upward facing surface of the coral and elevated on the sides. Oxygen consumption
      in darkness was also greatest within the Ostreobium zone, as well as in the white
      skeleton zone immediately below the corallites. The rate of O2 depletion was not
      constant within zones and between zones, showing pronounced heterogeneity in
      endolithic respiration. When the coral was placed in darkness after a period of
      illumination, O2 levels declined by 50% within 20 min and approached steady-state
      after 40-50 min in darkness. Our study demonstrates the use of an important new
      tool in endolith photobiology and presents the first data of spatially resolved
      O2 concentration and its correlation to the physical structures and specific
      zones responsible for O2 production and consumption within the coral skeleton. 

PMID- 27041415
TI  - DIEL VARIATIONS IN OPTICAL PROPERTIES OF IMANTONIA ROTUNDA (HAPTOPHYCEAE) AND
      THALASSIOSIRA PSEUDONANA (BACILLARIOPHYCEAE) EXPOSED TO DIFFERENT IRRADIANCE
      LEVELS(1).
AB  - Diel variations of cellular optical properties were examined for cultures of the
      haptophyte Imantonia rotunda N. Reynolds and the diatom Thalassiosira pseudonana
      (Hust.) Hasle et Heimdal grown under a 14:10 light:dark (L:D) cycle and
      transferred from 100 MUmol photons . m(-2)  . s(-1) to higher irradiances of 250
      and 500 MUmol photons . m(-2)  . s(-1) . Cell volume and abundance, phytoplankton
      absorption coefficients, flow-cytometric light scattering and chl fluorescence,
      and pigment composition were measured every 2 h over a 24 h period. Results
      showed that cell division was more synchronous for I. rotunda than for T.
      pseudonana. Several variables exhibited diel variability with an amplitude >100%,
      notably mean cell volume for the haptophyte and photoprotective carotenoids for
      both species, while optical properties such as flow-cytometric scattering and chl
      a-specific phytoplankton absorption generally showed <50% diel variability.
      Increased irradiance induced changes in pigments (both species) and mean cell
      volume (for the diatom) and amplified diel variability for most variables. This
      increase in amplitude is larger for pigments (factor of 2 or more, notably for
      cellular photoprotective carotenoid content in I. rotunda and for photosynthetic
      pigments in T. pseudonana) than for optical properties (a factor of 1.5 for chl a
      specific absorption, at 440 nm, in I. rotunda and a factor of 2 for the
      absorption cross-section and the chl a-specific scattering in T. pseudonana).
      Consequently, diel changes in optical properties and pigmentation associated with
      the L:D cycle and amplified by concurrent changes in irradiance likely contribute
      significantly to the variability in optical properties observed in biooptical
      field studies. 

PMID- 27041416
TI  - ALGAL RESPONSE TO NUTRIENT ENRICHMENT IN FORESTED OLIGOTROPHIC STREAM(1).
AB  - Nutrient input in streams alters the density and species composition of attached
      algal communities in open systems. However, in forested streams, the light
      reaching the streambed (rather than the local nutrient levels) may limit the
      growth of these communities. A nutrient-enrichment experiment in a forested
      oligotrophic stream was performed to test the hypothesis that nutrient addition
      has only minor effects on the community composition of attached algae and
      cyanobacteria under light limitation. Moderate nutrient addition consisted of
      increasing basal phosphorus (P) concentrations 3-fold and basal nitrogen (N)
      concentrations 2-fold. Two upstream control reaches were compared to a downstream
      reach before and after nutrient addition. Nutrients were added continuously to
      the downstream reach for 1 year. Algal biofilms growing on ceramic tiles were
      sampled and identified for more than a year before nutrient addition to 12 months
      after. Diatoms were the most abundant taxonomic group in the three stream
      reaches. Nutrient enrichment caused significant variations in the composition of
      the diatom community. While some taxa showed significant decreases (e.g.,
      Achnanthes minutissima, Gomphonema angustum), increases for other taxa (such as
      Rhoicosphenia abbreviata and Amphora ovalis) were detected in the enriched reach
      (for taxonomic authors, see Table 2). Epiphytic and adnate taxa of large size
      were enhanced, particularly during periods of favorable growth conditions
      (spring). Nutrients also caused a change in the algal chl a, which increased from
      0.5-5.8 to 2.1-10.7 MUg chl . cm(-2) . Our results indicate that in oligotrophic
      forested streams, long-term nutrient addition has significant effects on the
      algal biomass and community composition, which are detectable despite the low
      light availability caused by the tree canopy. Low light availability moderates
      but does not detain the long-term tendency toward a nutrient-tolerant community.
      Furthermore, the effects of nutrient addition on the algal community occur in
      spite of seasonal variations in light, water flow, and water chemical
      characteristics, which may confound the observations. [Table: see text]. 

PMID- 27041417
TI  - PHOTOSYNTHESIS AND RESPIRATION OF THE CONCHOCELIS STAGE OF ALASKAN PORPHYRA
      (BANGIALES, RHODOPHYTA) SPECIES IN RESPONSE TO ENVIRONMENTAL VARIABLES(1).
AB  - Photosynthesis and respiration of three Alaskan Porphyra species, P. abbottiae V.
      Krishnam., P. pseudolinearis Ueda species complex (identified as P.
      "pseudolinearis" below), and P. torta V. Krishnam., were investigated under a
      range of environmental parameters. Photosynthesis versus irradiance (P-I) curves
      revealed that maximal photosynthesis (Pmax ), irradiance at maximal
      photosynthesis (Imax ), and compensation irradiance (Ic ) varied with salinity,
      temperature, and species. The Pmax of Porphyra abbottiae conchocelis varied
      between 83 and 240 MUmol O2  . g dwt(-1)  . h(-1) (where dwt indicates dry
      weight) at 30-140 MUmol photons . m(-2)  . s(-1) (Imax ) depending on
      temperature. Higher irradiances resulted in photoinhibition. Maximal
      photosynthesis of the conchocelis of P. abbottiae occurred at 11 degrees C, 60
      MUmol photons . m(-2) .s(-1) , and 30 psu (practical salinity units). The
      conchocelis of P. "pseudolinearis" and P. torta had similar Pmax values but
      higher Imax values than those of P. abbottiae. The Pmax of P. "pseudolinearis"
      conchocelis was 200-240 MUmol O2  . g dwt(-1)  . h(-1) and for P. torta was 90
      240 MUmol O2  . g dwt(-1)  . h(-1) . Maximal photosynthesis for P.
      "pseudolinearis" occurred at 7 degrees C and 250 MUmol photons . m(-2)  . s(-1)
      at 30 psu, but Pmax did not change much with temperature. Maximal photosynthesis
      for P. torta occurred at 15 degrees C, 200 MUmol photons . m(-2)  . s(-1) , and
      30 psu. Photosynthesis rates for all species declined at salinities <25 or >35
      psu. Estimated compensation irradiances (Ic ) were relatively low (3-5 MUmol .
      photons . m(-2)  . s(-1) ) for intertidal macrophytes. Porphyra conchocelis had
      lower respiration rates at 7 degrees C than at 11 degrees C or 15 degrees C. All
      three species exhibited minimal respiration rates at salinities between 25 and 35
      psu. 

PMID- 27041418
TI  - TRANSPORT AND DEFENSIVE ROLE OF ELATOL AT THE SURFACE OF THE RED SEAWEED
      LAURENCIA OBTUSA (CERAMIALES, RHODOPHYTA)(1).
AB  - Natural within-thallus concentrations of elatol produced by Laurencia obtusa
      (Huds.) J. V. Lamour. inhibit herbivory and prevent fouling. However, elatol
      occurs in larger amounts within the thallus compared with the quantities from the
      surface of this alga. We evaluated whether the surface elatol concentrations
      inhibit both herbivory and fouling and whether the content of corps en cerise can
      be transferred to the external cell walls. Surface elatol concentrations did not
      inhibit herbivory by sea urchins, settlement of barnacle larvae, or mussel
      attachment. Evidence of a connection between the corps en cerise, where elatol is
      probably stored, and the cell wall of L. obtusa was based on channel-like
      membranous connections that transport vesicles from the corps to the cell wall
      region. Therefore, L. obtusa presents a specific process of chemical transport
      between the cell storage structures and the plant surface. We hypothesized that
      if high amounts of elatol are capable of inhibiting herbivory and fouling, if the
      tested organisms are ecologically relevant, and if elatol really occurs on the
      surface of L. obtusa and this seaweed can transport this compound to its surface,
      the low natural concentration of defensive chemicals on the surface of L. obtusa
      is probably not absolute but may be variable according to environmental
      conditions. We also hypothesized that herbivory and fouling would not exert the
      same selective force for the production of defensive chemicals on L. obtusa's
      surface since the low concentrations of elatol were inefficient to inhibit either
      processes or distinguish selective pressures. 

PMID- 27041419
TI  - MARINE-DERIVED DINOFLAGELLATES IN ANTARCTIC SALINE LAKES: COMMUNITY COMPOSITION
      AND ANNUAL DYNAMICS(1) *[link].
AB  - The saline lakes of the Vestfold Hills in Antarctica offer a remarkable natural
      laboratory where the adaptation of planktonic protists to a range of evolving
      physiochemical conditions can be investigated. This study illustrates how an
      ancestral marine community has undergone radical simplification leaving a small
      number of well-adapted species. Our objective was to investigate the species
      composition and annual dynamics of dinoflagellate communities in three saline
      Antarctic lakes. We observed that dinoflagellates occur year-round despite
      extremely low PAR during the southern winter, which suggests significant
      mixotrophic or heterotrophic activity. Only a small number of dominant
      dinoflagellate species were found in each lake, in contrast to the species-rich
      Southern Ocean from which the lake communities are believed to be derived. We
      verified that the lake species were representatives of the marine polar
      dinoflagellate community, and not freshwater species. Polarella glacialis
      Montresor, Procaccini et Stoecker, a bipolar marine species, was for the first
      time described in a lake habitat and was an important phototrophic component in
      the higher salinity lakes. In the brackish lakes, we found a new sibling species
      to the brackish-water species Scrippsiella hangoei (J. Schiller) J. Larsen,
      previously observed only in the Baltic Sea. 

PMID- 27041420
TI  - POPULATION DYNAMICS OF GREEN NOCTILUCA SCINTILLANS (DINOPHYCEAE) ASSOCIATED WITH
      THE MONSOON CYCLE IN THE UPPER GULF OF THAILAND(1).
AB  - Population dynamics of Noctiluca scintillans (Macartney) Kof. et Swezy containing
      the photosynthetic endosymbiont Pedinomonas noctilucae (Subrahman.) Sweeney was
      investigated in relation to environmental conditions in the upper Gulf of
      Thailand. A clear association was observed between the abundance of N.
      scintillans and the monsoon cycle, with its blooms occurring during the southwest
      (SW) monsoon from May to September, and low abundance during the northeast (NE)
      monsoon from November to February. Nutrient concentrations were higher during the
      SW monsoon than during the NE monsoon due to the combined effect of increased
      river discharge into the northern upper gulf and the transport of the riverine
      inputs by the prevailing clockwise circulation of the water. These nutrient
      conditions favored the growth of both phytoplankton and the endosymbiont.
      Correlation analysis revealed that the higher abundance of N. scintillans in the
      SW monsoon was manifested primarily by higher growth through both sexual and
      asexual reproduction supported by phagotrophy. However, the dependence of N.
      scintillans on the nutrient concentration was not significant, probably because
      the nutrient supply for the endosymbiont was sufficient due to intracellular
      accumulation of nutrients within the host cells. Sexual reproduction occurred
      only during the SW monsoon, and its potential importance in population growth was
      suggested. These findings showed the bottom-up control of the population dynamics
      of N. scintillans through growth of phytoplankton as prey. The seasonal shift in
      the circulation pattern associated with the monsoon cycle played a crucial role
      in blooming of N. scintillans by producing favorable food conditions. 

PMID- 27041421
TI  - ALGAE AS COMPETITORS FOR GLUCOSE WITH HETEROTROPHIC BACTERIA(1).
AB  - Dissolved organic carbon (DOC) constitutes the bulk of organic carbon in aquatic
      environments. The importance of DOC utilization by mixotrophic algae is unclear
      since heterotrophic bacteria are regarded as more efficient users. We tested the
      hypothesis that algae decrease the DOC concentration in the light to lower levels
      than in darkness resulting in competitive exclusion of heterotrophic bacteria
      according to the mechanistic competition theory. We investigated (a) the uptake
      kinetics of glucose as a model substrate by two cultured algae and mixed bacteria
      populations, (b) the competition for glucose between algae and bacteria in
      chemostats, (c) the effect of discontinuous glucose supply in chemostats, and (d)
      the minimum glucose concentrations achieved in cultures of algae and bacteria.
      Bacteria showed higher specific-glucose-uptake rates than algae. In chemostats,
      algae became extinct in the dark and coexisted in the light where they decreased
      bacteria to lower densities. Discontinuous glucose supply promoted the algae
      compared to continuous substrate addition. Several algae consumed glucose to
      lower concentrations in the dark than in the light and showed lower or equal
      residual glucose concentrations than bacteria. Residual concentrations were not
      related to allometric traits (cell volume) and photosynthetic potential (chl
      content). Overall, the hypothesis was not supported, and mechanisms of
      competition for DOC obviously differed from those for particulate prey. However,
      since some algae showed lower or equal residual glucose concentrations than
      bacteria, algal dark uptake of DOC may be important in deep layers of many
      waters. 

PMID- 27041422
TI  - DEMOGRAPHIC CONSEQUENCES OF COALESCENCE IN SPORELING POPULATIONS OF MAZZAELLA
      LAMINARIOIDES (GIGARTINALES, RHODOPHYTA)(1).
AB  - Coalescing macroalgae are ecologically important members of intertidal and
      shallow subtidal communities. However, we still lack quantitative information on
      the demographic consequences of coalescence. Using demographic models developed
      for modular invertebrates, we studied the demography of settlement and early
      recruitment in the coalescing macroalga Mazzaella laminarioides (Bory) Fredericq.
      Permanently marked microscopic fields on laboratory-incubated and field-incubated
      plates were monitored regularly (at 15, 30, 45, and 60 d) using image analysis
      techniques to evaluate the relative importance of settler abundance, mortality,
      coalescence (fusion), and fission on the changes in size and numbers of recruits.
      On the plates, spores settled individually or in groups. Over time, spores in
      close proximity may coalesce, resulting in a mixture of unisporic and multisporic
      crusts. When new spores arrive, they may or may not coalesce with previously
      settled crusts. Coalescence and mortality reduce the number of sporelings, but
      coalescence increases the size of the sporelings, thereby reducing further
      probability of sporeling mortality. Crust fissions are negligible in frequency,
      while the frequency of coalescence increases from ~25% after only 3 d, to ~75%
      after 60 d. Thus, as a result of variable settlement, mortality, and coalescence,
      any area colonized by M. laminarioides would contain a mixture of crusts of
      different sizes, ages, and genetic constitution. The interactions between the
      above three processes create a more complex survivorship curve than the ones
      known for unitary organisms. 

PMID- 27041423
TI  - IDENTIFICATION AND ASSESSMENT OF DOMOIC ACID PRODUCTION IN OCEANIC PSEUDO
      NITZSCHIA (BACILLARIOPHYCEAE) FROM IRON-LIMITED WATERS IN THE NORTHEAST SUBARCTIC
      PACIFIC(1).
AB  - We identified and investigated the potential toxicity of oceanic Pseudo-nitzschia
      species from Ocean Station Papa (OSP), located in a high-nitrate, low-chlorophyll
      (HNLC) region of the northeast (NE) subarctic Pacific Ocean. Despite their
      relatively low abundances in the indigenous phytoplankton assemblage, Pseudo
      nitzschia species richness is high. The morphometric characteristics of five
      oceanic Pseudo-nitzschia isolates from at least four species are described using
      SEM and TEM. The species identified are Pseudo-nitzschia dolorosa Lundholm et
      Moestrup, P. granii Hasle, P. heimii Manguin, and P. cf. turgidula (Hust.) Hasle.
      Additional support for the taxonomic classifications based on frustule morphology
      is provided through the sequencing of the internal transcribed spacer 1 (ITS1)
      rDNA. Pseudo-nitzschia species identification was also assessed by the
      construction of ITS1 clone libraries and using automated ribosomal intergenic
      spacer analysis (ARISA) for environmental samples collected during the Subarctic
      Ecosystem Response to Iron Enrichment Study (SERIES), conducted in close
      proximity to OSP in July of 2002. Based on ITS1 sequences, the presence of P.
      granii, P. heimii, P. cf. turgidula, and at least five other putative,
      unidentified Pseudo-nitzschia ITS1 variants was confirmed within iron-enriched
      phytoplankton assemblages at OSP. None of the oceanic isolates produced
      detectable levels of particulate domoic acid (DA) when in prolonged stationary
      phase due to silicic acid starvation. The lack of detectable concentrations of DA
      suggests that either these strains produce very little or no toxin, or that the
      physiological conditions required to promote particulate DA production were not
      met and thus differ from their coastal, toxigenic congeners. 

PMID- 27041424
TI  - INTERACTIONS AMONG PHOSPHATE UPTAKE, PHOTOSYNTHESIS, AND CHLOROPHYLL FLUORESCENCE
      IN NUTRIENT-LIMITED CULTURES OF THE CHLOROPHYTE MICROALGA DUNALIELLA
      TERTIOLECTA(1).
AB  - Phosphate-limited and phosphate-sufficient continuous cultures of the marine
      chlorophyte microalga Dunaliella tertiolecta Butcher were examined for their
      responses to the addition of phosphate. Phosphate-limited cultures showed a
      marked quenching of chl fluorescence following a pulse of phosphate. This
      response was absent from cells growing under phosphate-sufficient conditions.
      Both the extent of fluorescence quenching (where present) and the initial rate of
      change in quenching were dependent on the concentration of phosphate added to
      cell suspensions and on the degree of limitation (growth rate in continuous
      culture). The addition of phosphate also brought about a transient decrease in
      photosynthetic oxygen evolution and a stimulation in respiration, which were
      relaxed as the added phosphate was depleted from the external medium. The
      applicability of using nutrient-induced fluorescence transients as a tool to
      identify the nutrient status of phytoplankton populations is discussed. 

PMID- 27041425
TI  - PHOTOINHIBITION OF PSII IN EMILIANIA HUXLEYI (HAPTOPHYTA) UNDER HIGH LIGHT
      STRESS: THE ROLES OF PHOTOACCLIMATION, PHOTOPROTECTION, AND PHOTOREPAIR(1).
AB  - The response of the coccolithophorid Emiliania huxleyi (Lohmann) W. H. Hay et H.
      Mohler to acute exposure to high photon flux densities (PFD) was examined in
      terms of PSII photoinhibition, photoprotection, and photorepair. The time and
      light dependencies of these processes were characterized as a function of the
      photoacclimation state of the alga. Low-light (LL) acclimated cells displayed a
      higher degree of photoinhibition, measured as decline in Fv /Fm , than high-light
      (HL) acclimated cells. However, HL cultures were more susceptible to photodamage
      but also more capable of compensating for it by performing a faster repair cycle.
      The relation between gross photoinhibition (observed in the presence of an
      inhibitor of repair) and PFD to which the algae were exposed deviated from
      linearity at high PFD, which calls into question the universality of current
      concepts of photoinhibition in mechanistic models. The light dependence of the de
      epoxidation state (DPS) of the xanthophyll cycle (XC) pigments on the timescale
      of hours was the same in cells acclimated to LL and HL. However, HL cells were
      more efficient in realizing nonphotochemical quenching (NPQ) on short timescales,
      most likely due to a larger XC pool. LL cells displayed an increase in the PSII
      effective cross-section (sigmaPSII ) as a result of photoinhibition, which was
      observed also in HL cells when net photoinhibition was induced by blocking the D1
      repair cycle. The link between sigmaPSII and photoinhibition suggests that the
      population of PSII reaction centers (RCIIs) of E. huxleyi shares a common
      antenna, according to a "lake" organization of the light-harvesting complex. 

PMID- 27041426
TI  - ISOLATION AND CHARACTERIZATION OF THE PHYTOENE DESATURASE GENE AS A POTENTIAL
      SELECTIVE MARKER FOR GENETIC ENGINEERING OF THE ASTAXANTHIN-PRODUCING GREEN ALGA
      CHLORELLA ZOFINGIENSIS (CHLOROPHYTA)(1).
AB  - Phytoene desaturase (PDS) is a rate-limiting enzyme in carotenoid biosynthesis.
      Algal PDS is inhibited by some herbicides, leading to the bleaching of the cells
      due to destruction of chl. Specific point mutations in PDS confer resistance to
      the herbicide norflurazon, suggesting that mutated PDS could be used as a
      dominant selectable marker for genetic engineering of algae, for which very few
      selective markers are available. In this study, we report the isolation and
      characterization of the PDS gene from the astaxanthin-producing green alga
      Chlorella zofingiensis Donz. The open reading frame (ORF) of this PDS gene,
      interrupted by six introns, encoded a polypeptide of 558 amino acid residues. The
      deduced protein sequence showed significant homology to phytoene desaturases of
      algae, cyanobacteria, and higher plants. Expression of the PDS gene in
      Escherichia coli demonstrated that the enzyme was able to convert phytoene to
      zeta-carotene. The PDS gene in Chlorella was shown to be up-regulated by high
      light and glucose treatment. With a single amino acid change (L516R), the mutated
      PDS-L516R was still active and exhibited ~36-fold greater resistance to the
      bleaching herbicide norflurazon than the unaltered enzyme. Thus, the modified PDS
      gene could be a useful tool for genetic engineering of carotenoid biosynthesis in
      C. zofingiensis and perhaps also in other algae. 

PMID- 27041427
TI  - SEXUALITY AND UNIPARENTAL INHERITANCE OF CHLOROPLAST DNA IN THE ISOGAMOUS GREEN
      ALGA ULVA COMPRESSA (ULVOPHYCEAE)(1).
AB  - Ulva compressa L. is a heterothallic macroalga considered to be in the early
      evolutionary stage between isogamy and anisogamy. Two genetic lines of this
      species, each consisting of gametophytes with opposite mating types, were
      collected on the coasts of Ehime and Iwate prefectures: MGEC-1 (mt(+) ) and MGEC
      2 (mt(-) ) from Ehime, and MGEC-5 (mt(+) ) and MGEC-6 (mt(-) ) from Iwate. Their
      relative gamete sizes (i.e., cell volumes) do not correspond to their mating
      types: MGEC-6 (19.8 MUm(3) ) > MGEC-1 (18.6 MUm(3) ) > MGEC-5 (17.0 MUm(3) ) >
      MGEC-2 (10.1 MUm(3) ). The pattern of organelle inheritance is an important
      sexual characteristic in many eukaryotes. We therefore investigated the
      relationship between gamete size and the inheritance of chloroplast DNA (cpDNA).
      Polymorphisms between the cpDNA of the two lines were used as markers. We found a
      24 bp insertion between psbF and psbL, and the substitution of a StyI site (from
      CCAAGG to TCAAGG) in the intergenic region between petD and accD. Two interline
      crosses (MGEC-1 * MGEC-6 and MGEC-2 * MGEC-5) produced 42 and 38 zygotes,
      respectively. PCR and PCR-RFLP analyses showed that the cpDNA of the mt(+)
      gametes was consistently inherited in both crosses. The cpDNA is inherited from
      one parent only, and it depends not on gamete size but on being mt(+) . The cpDNA
      was observed during crossing and in the zygotes 6 h after mating. In 6% of the
      zygotes, the cpDNA derived from the mt(-) gametes disappeared 3-4 h after mating.
      Preferential digestion of the cpDNA in the zygote's mt(-) gamete may form the
      basis for uniparental inheritance of cpDNA. 

PMID- 27041428
TI  - mRNA EDITING AND SPLICED-LEADER RNA TRANS-SPLICING GROUPS OXYRRHIS, NOCTILUCA,
      HETEROCAPSA, AND AMPHIDINIUM AS BASAL LINEAGES OF DINOFLAGELLATES(1).
AB  - Identification of novel dinoflagellate taxa through molecular analysis is
      hindered by lack of well-defined basal lineages. To address this issue, we
      attempted to reassess the phylogenetic status of Oxyrrhis marina Dujard. as well
      as other potentially basal taxa. The analysis was based on two newly established
      premises: (1) editing density of mitochondrial cob and cox1 mRNA increases from
      basal to later diverging lineages; (2) nuclear-encoded mRNA in dinoflagellates is
      trans-spliced to receive a 22 bp spliced leader (SL) at the 5'-end. We analyzed
      these two genetic traits in O. marina, Noctiluca scintillans (Macartney) Kof. et
      Swezy, Heterocapsa triquetra (Ehrenb.) F. Stein, H. rotundata (Lohmann) Ge.
      Hansen, Amphidinium carterae Hulburt, and A. operculatum Clap. et J. Lachm.
      Surprisingly, no editing was detected in cob and cox1 mRNAs in these lineages,
      except for a small number of editing events in Amphidinium. However, nuclear
      encoded mRNAs in these species contained the SL sequence at the 5'-end,
      indicative of SL RNA trans-splicing. These findings, together with the recent cob
      cox1-18S rRNA three-gene phylogeny, suggest the following: (1) O. marina is a
      basal dinoflagellate; (2) Heterocapsa, Amphidinium, and Noctiluca likely are also
      early diverging lineages of dinoflagellates, and the position of Heterocapsa is
      inconsistent with literature and needs further investigation; and (3) the
      presence of the 22 bp SL and mitochondrial (mt) mRNA editing can be considered a
      landmark of dinoflagellate splits. 

PMID- 27041429
TI  - THE OOGONIA OF MACROALGA UNDARIA PINNATIFIDA ARE ALKALINE-PHOSPHATASE POSITIVE
      AND CONTAIN GERMINAL BODY-LIKE STRUCTURES(1).
AB  - It was observed that in the female gametophyte of Undaria pinnatifida (Harv.)
      Suringar (Phaeophyta, Laminariales) gametangial initials and maturing oogonia
      demonstrated different levels of alkaline-phosphatase activity (APA). The oogonia
      exhibited a higher level of APA than in its initials. Electron-dense granular
      ovoid structures ~0.5-0.6 MUm were present in the cytoplasm of oogonia. These
      inclusions were not membrane bound and do not appear to be associated with any
      particular organelles. The number of the inclusions was 1 to 2 in a single
      section of the cell. In essential details, the specific APA and subcellular
      germinal body-like structure of the developing female gamete in U. pinnatifida
      were very similar to those in metazoan oocytes. 

PMID- 27041430
TI  - CHANGES IN THE MORPHOLOGY AND POLYSACCHARIDE CONTENT OF MICROCYSTIS AERUGINOSA
      (CYANOBACTERIA) DURING FLAGELLATE GRAZING(1).
AB  - To investigate the changes in the morphology and polysaccharide content of
      Microcystis aeruginosa (Kutz.) Kutz. during flagellate grazing, cultures of M.
      aeruginosa were exposed to grazing Ochromonas sp. for a period of 9 d under
      controlled laboratory conditions. M. aeruginosa responded actively to flagellate
      grazing and formed colonies, most of which were made up of several or dozens of
      cells, suggesting that flagellate grazing may be one of the biotic factors
      responsible for colony formation in M. aeruginosa. When colonies were formed, the
      cell surface ultrastructure changed, and the polysaccharide layer on the surface
      of the cell wall became thicker. This change indicated that synthesis and
      secretion of extracellular polysaccharide (EPS) of M. aeruginosa cells increased
      under flagellate grazing pressure. The contents of soluble extracellular
      polysaccharide (sEPS), bound extracellular polysaccharide (bEPS), and total
      polysaccharide (TPS) in colonial cells of M. aeruginosa increased significantly
      compared with those in single cells. This finding suggested that the increased
      amount of EPS on the cell surface may play a role in keeping M. aeruginosa cells
      together to form colonies. 

PMID- 27041431
TI  - GAYLIELLA GEN. NOV. IN THE TRIBE CERAMIEAE (CERAMIACEAE, RHODOPHYTA) BASED ON
      MOLECULAR AND MORPHOLOGICAL EVIDENCE(1).
AB  - On the basis of comparative morphology and phylogenetic analyses of rbcL and LSU
      rDNA sequence data, a new genus, Gayliella gen. nov., is proposed to accommodate
      the Ceramium flaccidum complex (C. flaccidum, C. byssoideum, C. gracillimum var.
      byssoideum, and C. taylorii), C. fimbriatum, and a previously undescribed species
      from Australia. C. transversale is reinstated and recognized as a distinct
      species. Through this study, G. flaccida (Kutzing) comb. nov., G. transversalis
      (Collins et Hervey) comb. nov., G. fimbriata (Setchell et N. L. Gardner) comb.
      nov., G. taylorii comb. nov., G. mazoyerae sp. nov., and G. womersleyi sp. nov.
      are based on detailed comparative morphology. The species referred to as C.
      flaccidum and C. dawsonii from Brazil also belong to the new genus. Comparison of
      Gayliella with Ceramium shows that it differs from the latter by having an
      alternate branching pattern; three cortical initials per periaxial cell, of which
      the third is directed basipetally and divides horizontally; and unicellular
      rhizoids produced from periaxial cells. Our phylogenetic analyses of rbcL and LSU
      rDNA gene sequence data confirm that Gayliella gen. nov. represents a
      monophyletic clade distinct from most Ceramium species including the type
      species, C. virgatum. We also transfer C. recticorticum to the new genus
      Gayliella. 

PMID- 27041432
TI  - DEEP DIVISION IN THE CHLOROPHYCEAE (CHLOROPHYTA) REVEALED BY CHLOROPLAST
      PHYLOGENOMIC ANALYSES(1).
AB  - The Chlorophyceae (sensu Mattox and Stewart) is a morphologically diverse class
      of the Chlorophyta displaying biflagellate and quadriflagellate motile cells with
      varying configurations of the flagellar apparatus. Phylogenetic analyses of 18S
      rDNA data and combined 18S and 26S rDNA data from a broad range of chlorophycean
      taxa uncovered five major monophyletic groups (Chlamydomonadales, Sphaeropleales,
      Oedogoniales, Chaetophorales, and Chaetopeltidales) but could not resolve their
      branching order. To gain insight into the interrelationships of these groups, we
      analyzed multiple genes encoded by the chloroplast genomes of Chlamydomonas
      reinhardtii P. A. Dang. and Chlamydomonas moewusii Gerloff (Chlamydomonadales),
      Scenedesmus obliquus (Turpin) Kutz. (Sphaeropleales), Oedogonium cardiacum Wittr.
      (Oedogoniales), Stigeoclonium helveticum Vischer (Chaetophorales), and Floydiella
      terrestris (Groover et Hofstetter) Friedl et O'Kelly (Chaetopeltidales). The C.
      moewusii, Oedogonium, and Floydiella chloroplast DNAs were partly sequenced using
      a random strategy. Trees were reconstructed from nucleotide and amino acid data
      sets derived from 44 protein-coding genes of 11 chlorophytes and nine
      streptophytes as well as from 57 protein-coding genes of the six chlorophycean
      taxa. All best trees identified two robustly supported major lineages within the
      Chlorophyceae: a clade uniting the Chlamydomonadales and Sphaeropleales, and a
      clade uniting the Oedogoniales, Chaetophorales, and Chaetopeltidales (OCC clade).
      This dichotomy is independently supported by molecular signatures in chloroplast
      genes, such as insertions/deletions and the distribution of trans-spliced group
      II introns. Within the OCC clade, the sister relationship observed for the
      Chaetophorales and Chaetopeltidales is also strengthened by independent data.
      Character state reconstruction of basal body orientation allowed us to refine
      hypotheses regarding the evolution of the flagellar apparatus. 

PMID- 27041433
TI  - MOLECULAR PHYLOGENY, ULTRASTRUCTURE, AND TAXONOMIC REVISION OF CHLOROGONIUM
      (CHLOROPHYTA): EMENDATION OF CHLOROGONIUM AND DESCRIPTION OF GUNGNIR GEN. NOV.
      AND RUSALKA GEN. NOV.(1).
AB  - We examined the molecular phylogeny and ultrastructure of Chlorogonium and
      related species to establish the natural taxonomy at the generic level.
      Phylogenetic analyses of 18S rRNA and RUBISCO LSU (rbcL) gene sequences revealed
      two separate clades of Chlorogonium from which Chlorogonium (Cg.) fusiforme Matv.
      was robustly separated. One clade comprised Cg. neglectum Pascher and Cg. kasakii
      Nozaki, whereas the other clade included the type species Cg. euchlorum (Ehrenb.)
      Ehrenb., Cg. elongatum (P. A. Dang.) France, and Cg. capillatum Nozaki, M.
      Watanabe et Aizawa. On the basis of unique ultrastructural characteristics, we
      described Gungnir Nakada gen. nov. comprising three species: G. neglectum
      (Pascher) Nakada comb. nov., G. mantoniae (H. Ettl) Nakada comb. nov., and G.
      kasakii (Nozaki) Nakada comb. nov. We also emended Chlorogonium as a monophyletic
      genus composed of Cg. euchlorum, Cg. elongatum, and Cg. capillatum. Because Cg.
      fusiforme was distinguished from the redefined Chlorogonium and Gungnir by the
      structure of its starch plate, which is associated with pyrenoids, we
      reclassified this species as Rusalka fusiformis (Matv.) Nakada gen. et comb. nov.

PMID- 27041434
TI  - PHYLOGENETIC ANALYSIS OF THE LARGE SUBUNIT RUBISCO GENE SUPPORTS THE EXCLUSION OF
      AVRAINVILLEA AND CLADOCEPHALUS FROM THE UDOTEACEAE (BRYOPSIDALES,
      CHLOROPHYTA)(1).
AB  - The placement of Avrainvillea and Cladocephalus in the family Udoteaceae (order
      Bryopsidales) has been questioned on the basis of nuclear, plastid, and other
      ultrastructural characteristics unique to these genera. Bayesian analysis of the
      chloroplast-encoded LSU RUBISCO (rbcL) gene showed that the Udoteaceae is
      paraphyletic. Cladocephalus luteofuscus (P. Crouan et H. Crouan) Borgesen,
      Avrainvillea nigricans f. floridana D. Littler et Littler, and A. mazei G. Murray
      et Boodle form a clade with the freshwater alga Dichotomosiphon tuberosus (A.
      Braun ex Kutz.) A. Ernst that is basal to a clade that includes other members of
      the Udoteaceae, the Halimedaceae, and the Caulerpaceae. The noncalcified species
      Boodleopsis pusilla (Collins) W. R. Taylor, A. B. Joly et Bernat. groups with
      species of the calcified Udoteacean genera Penicillus, Rhipocephalus, Udotea, and
      Halimeda. 

PMID- 27041435
TI  - CONDITIONAL PRODUCTION OF A FUNCTIONAL FISH GROWTH HORMONE IN THE TRANSGENIC LINE
      OF NANNOCHLOROPSIS OCULATA (EUSTIGMATOPHYCEAE)(1).
AB  - Plasmid phr-YPGHc, containing the fish growth hormone (GH) cDNA driven by a heat
      shock protein 70A promoter and a RUBISCO SSU 2 promoter, was transferred into the
      protoplast of marine microalga Nannochloropsis oculata (Droop) D. J. Hibberd by
      electroporation. Four transgenic clones were obtained in which the transferred
      phr-YPGHc was integrated into the genome and existed stably at least until the
      50th generation. When we treated these transgenic microalgae by heat shock, the
      heterologous fish GH was produced in the amount of 0.42 to 0.27 MUg . mL(-1) from
      the 50 mL of medium. We incubated artemia with the wildtype and transgenic N.
      oculata for 6 h and then fed these microalgae-treated artemia to red-tilapia
      larvae. After feeding, the growth of larvae that were fed artemia incubated with
      transgenic microalgae was greater (i.e., statistically significant: P < 0.05)
      than that of larvae that were fed artemia incubated with nontransgenic
      microalgae: 316% versus 104% in weight gain, and 217% versus 146% in body length
      increase, respectively. Therefore, the N. oculata enables production of
      functional GH, and we propose that it might be an excellent bioreactor material. 

PMID- 27041436
TI  - COMBINED EFFECTS OF ULTRAVIOLET RADIATION AND TEMPERATURE ON MORPHOLOGY,
      PHOTOSYNTHESIS, AND DNA OF ARTHROSPIRA (SPIRULINA) PLATENSIS (CYANOPHYTA)(1).
AB  - Natural levels of solar UVR were shown to break and alter the spiral structure of
      Arthrospira (Spirulina) platensis (Nordst.) Gomont during winter. However, this
      phenomenon was not observed during summer at temperatures of ~30 degrees C. Since
      little has been documented on the interactive effects of solar UV radiation (UVR;
      280-400 nm) and temperature on cyanobacteria, the morphology, photosynthesis, and
      DNA damage of A. platensis were examined using two radiation treatments (PAR [400
      700 nm] and PAB [PAR + UV-A + UV-B: 280-700]), three temperatures (15, 22, and 30
      degrees C), and three biomass concentrations (100, 160, and 240 mg dwt [dry
      weight] . L(-1) ). UVR caused a breakage of the spiral structure at 15 degrees C
      and 22 degrees C, but not at 30 degrees C. High PAR levels also induced a
      significant breakage at 15 degrees C and 22 degrees C, but only at low biomass
      densities, and to lesser extent when compared with the PAB treatment. A.
      platensis was able to alter its spiral structure by increasing helix tightness at
      the highest temperature tested. The photochemical efficiency was depressed to
      undetectable levels at 15 degrees C but was relatively high at 30 degrees C even
      under the treatment with UVR in 8 h. At 30 degrees C, UVR led to 93%-97% less DNA
      damage when compared with 15 degrees C after 8 h of exposure. UV-absorbing
      compounds were determined as negligible at all light and temperature
      combinations. The possible mechanisms for the temperature-dependent effects of
      UVR on this organism are discussed in this paper. 

PMID- 27041437
TI  - COMPARISON OF SIMPLE AND MULTIMETRIC DIATOM-BASED INDICES FOR GREAT LAKES
      COASTLINE DISTURBANCE(1).
AB  - Because diatom communities are subject to the prevailing water quality in the
      Great Lakes coastal environment, diatom-based indices can be used to support
      coastal-monitoring programs and paleoecological studies. Diatom samples were
      collected from Great Lakes coastal wetlands, embayments, and high-energy sites
      (155 sites), and assemblages were characterized to the species level. We defined
      42 metrics on the basis of autecological and functional properties of species
      assemblages, including species diversity, motile species, planktonic species,
      proportion dominant taxon, taxonomic metrics (e.g., proportion Stephanodiscoid
      taxa), and diatom-inferred (DI) water quality (e.g., DI chloride [Cl]). Redundant
      metrics were eliminated, and a diatom-based multimetric index (MMDI) to infer
      coastline disturbance was developed. Anthropogenic stresses in adjacent coastal
      watersheds were characterized using geographic information system (GIS) data
      related to agricultural and urban land cover and atmospheric deposition. Fourteen
      independent diatom metrics had significant regressions with watershed stressor
      data; these metrics were selected for inclusion in the MMDI. The final MMDI was
      developed as the weighted sum of the selected metric scores with weights based on
      a metric's ability to reflect anthropogenic stressors in the adjacent watersheds.
      Despite careful development of the multimetric approach, verification using a
      test set of sites indicated that the MMDI was not able to predict watershed
      stressors better than some of the component metrics. From this investigation, it
      was determined that simpler, more traditional diatom-based metrics (e.g., DI Cl,
      proportion Cl-tolerant species, and DI total phosphorus [TP]) provide superior
      prediction of overall stressor influence at coastal locales. 

PMID- 27041438
TI  - RATE OF O2 PRODUCTION DERIVED FROM PULSE-AMPLITUDE-MODULATED FLUORESCENCE:
      TESTING THREE BIOOPTICAL APPROACHES AGAINST MEASURED O2 -PRODUCTION RATE(1).
AB  - Light absorption by phytoplankton is both species specific and affected by
      photoacclimational status. To estimate oxygenic photosynthesis from pulse
      amplitude-modulated (PAM) fluorescence, the amount of quanta absorbed by PSII
      needs to be quantified. We present here three different biooptical approaches to
      estimate the fraction of light absorbed by PSII: (1) the factor 0.5, which
      implies that absorbed light is equally distributed among PSI and PSII; (2) the
      fraction of chl a in PSII, determined as the ratio between the scaled red-peak
      fluorescence excitation and the red absorption peak; and (3) the measure of light
      absorbed by PSII, determined from the scaling of the fluorescence excitation
      spectra to the absorption spectra by the "no-overshoot" procedure. Three marine
      phytoplankton species were used as test organisms: Prorocentrum minimum (Pavill.)
      J. Schiller (Dinophyceae), Prymnesium parvum cf. patelliferum (J. C. Green, D. J.
      Hibberd et Pienaar) A. Larsen (Haptophyceae), and Phaeodactylum tricornutum
      Bohlin (Bacillariophyceae). Photosynthesis versus irradiance (P vs. E) parameters
      calculated using the three approaches were compared with P versus E parameters
      obtained from simultaneously measured rates of oxygen production. Generally,
      approach 1 underestimated, while approach 2 overestimated the gross O2 
      production rate calculated from PAM fluorescence. Approach 3, in principle the
      best approach to estimate quanta absorbed by PSII, was also superior according to
      observations. Hence, we recommend approach 3 for estimation of gross O2 
      production rates based on PAM fluorescence measurements. 

PMID- 27041439
TI  - TRANSIENT TRANSFORMATION OF A CHLORARACHNIOPHYTE ALGA, LOTHARELLA AMOEBIFORMIS
      (CHLORARACHNIOPHYCEAE), WITH uidA AND egfp REPORTER GENES(1).
AB  - A transient genetic transformation system was established for a
      chlorarachniophyte alga, Lotharella amoebiformis K. Ishida et Y. Hara. We first
      isolated sequences that contain a putative promoter for a RUBISCO SSU (rbcS) gene
      and a terminator for another copy of rbcS gene from L. amoebiformis. With those
      promoter and terminator sequences, we developed two expression vectors, pLaRGus
      and pLaRGfp, which code uidA and egfp genes, respectively. The cells were then
      transformed with each vector using a microparticle bombardment system. When the
      cells were transformed with the pLaRGus, beta-glucuronidase (GUS) staining dyed
      several cells blue. Green fluorescent protein (GFP) fluorescence was observed in
      the cells transformed with pLaRGfp. The highest transient transformation
      efficiency, 35 per 2 * 10(7) cells, was detected from the GUS staining. This
      study demonstrates that two reporter genes are expressed in L. amoebiformis cells
      when rbcS promoter and terminator are used. The conditions of transformation were
      also optimized. This is the first report of successful genetic transformation in
      chlorarachniophyte algae. 

PMID- 27041440
TI  - APPLICATION OF PHYLOGENETIC PRINCIPLES TO TESTING EVOLUTIONARY SCENARIOS: A
      COMMENT ON KACZMARSKA ET AL. "MOLECULAR PHYLOGENY OF SELECTED MEMBERS OF THE
      ORDER THALASSIOSIRALES (BACILLARIOPHYTA) AND EVOLUTION OF THE FULTOPORTULA"(1).
AB  - While rigorous techniques have usually been used to generate phylogenetic trees
      from molecular data, morphological analysis has sometimes been more informal. A
      recent example was a study of the evolution of the fultoportula in the diatom
      order Thalassiosirales (Kaczmarska et al. 2006). Phylogeny was inferred using
      modern phylogenetic principles applied to nuclear SSU rDNA sequences, but
      inferences about morphological character evolution were made using noncanonical
      reasoning and evolutionary scenario building. The preferred hypothesis posited
      that marginal fultoportulae evolved from the marginal ridge of Lithodesmiales. A
      related hypothesis suggested that fultoportulae in the valve center were not
      homologous with those near the valve margin. Shared symplesiomorphies, shared
      homoplasies, gaps in the fossil record, and subtle morphological differences
      between central- and marginal-area fultoportulae were offered as the primary
      evidence for these scenarios. The literature has demonstrated such arguments to
      be either irrelevant or logically weaker than inferences made under the tests of
      similarity, conjunction, and congruence. Five prior hypotheses about the origin
      and evolution of the fultoportula were examined in this study using these tests.
      The hypothesis that the areola evolved into the multistrutted process, which
      evolved into the fultoportula, was best supported. 

PMID- 27041441
TI  - Comparison of three analytical methods to measure the size of silver
      nanoparticles in real environmental water and wastewater samples.
AB  - Due to the widespread application of engineered nanoparticles, their potential
      risk to ecosystems and human health is of growing concern. Silver nanoparticles
      (Ag NPs) are one of the most extensively produced NPs. Thus, this study aims to
      develop a method to detect Ag NPs in different aquatic systems. In complex media,
      three emerging techniques are compared, including hydrodynamic chromatography
      (HDC), asymmetric flow field flow fractionation (AF4) and single particle
      inductively coupled plasma-mass spectrometry (SP-ICP-MS). The pre-treatment
      procedure of centrifugation is evaluated. HDC can estimate the Ag NP sizes, which
      were consistent with the results obtained from DLS. AF4 can also determine the
      size of Ag NPs but with lower recoveries, which could result from the
      interactions between Ag NPs and the working membrane. For the SP-ICP-MS, both the
      particle size and concentrations can be determined with high Ag NP recoveries.
      The particle size resulting from SP-ICP-MS also corresponded to the transmission
      electron microscopy observation (p>0.05). Therefore, HDC and SP-ICP-MS are
      recommended for environmental analysis of the samples after our established pre
      treatment process. The findings of this study propose a preliminary technique to
      more accurately determine the Ag NPs in aquatic environments and to use this
      knowledge to evaluate the environmental impact of manufactured NPs.

PMID- 27041442
TI  - Combined quartz crystal microbalance with dissipation (QCM-D) and generalized
      ellipsometry (GE) to characterize the deposition of titanium dioxide
      nanoparticles on model rough surfaces.
AB  - Measuring the interactions between engineered nanoparticles and natural
      substrates (e.g. soils and sediments) has been very challenging due to highly
      heterogeneous and rough natural surfaces. In this study, three-dimensional
      nanostructured slanted columnar thin films (SCTFs), with well-defined roughness
      height and spacing, have been used to mimic surface roughness. Interactions
      between titanium dioxide nanoparticles (TiO2NP), the most extensively
      manufactured engineered nanomaterials, and SCTF coated surfaces were measured
      using a quartz crystal microbalance with dissipation monitoring (QCM-D). In
      parallel, in-situ generalized ellipsometry (GE) was coupled with QCM-D to
      simultaneously measure the amount of TiO2NP deposited on the surface of SCTF.
      While GE is insensitive to effects of mechanical water entrapment variations in
      roughness spaces, we found that the viscoelastic model, a typical QCM-D model
      analysis approach, overestimates the mass of deposited TiO2NP. This
      overestimation arises from overlaid frequency changes caused by particle
      deposition as well as additional water entrapment and partial water displacement
      upon nanoparticle adsorption. Here, we demonstrate a new approach to model QCM-D
      data, accounting for both viscoelastic effects and the effects of roughness
      retained water. Finally, the porosity of attached TiO2NP layer was determined by
      coupling the areal mass density determined by QCM-D and independent GE
      measurements.

PMID- 27041443
TI  - Manufacturing conductive polyaniline/graphite nanocomposites with spent battery
      powder (SBP) for energy storage: A potential approach for sustainable waste
      management.
AB  - A potential approach for sustainable waste management of the spent battery
      material (SBM) is established for manufacturing conductive polyaniline (PANI)
      nanocomposites as electrode materials for supercapacitors, following the
      principle of "What comes from the power should be used for the power". The
      ternary nanocomposites (G/MnO2/PANI) containing PANI, graphite powder (G) and
      remanent MnO2 nanoparticles and the binary nanocomposites of polyaniline and
      graphite powder (G/PANI) are synthesized by the chemical oxidative polymerization
      of aniline in hydrochloric aqueous solution with the MnO2 nanoparticles in the
      spent battery powder (SBP) as oxidant. The G/PANI sample, which was prepared with
      MnO2/aniline mole ratio of 1:1 with 1.0mL aniline in 50mL of 1.0molL(-1) HCl,
      exhibits the electrical conductivity of 22.22Scm(-1), the highest specific
      capacitance up to 317Fg(-1) and the highest energy density of 31.0 Wh kg(-1),
      with retention of as high as 84.6% of its initial capacitance after 1000 cycles,
      indicating good cyclic stability.

PMID- 27041444
TI  - Introduction for Journal of Surgical Oncology Seminar Series: Value in surgical
      oncology.

PMID- 27041445
TI  - DFT study of the chlorine promotion effect on the ethylene adsorption over iron
      clusters.
AB  - This work explores how electronic perturbations induced by chlorine atoms can
      enhance the activity of iron toward ethylene. The metal clusters include Fen (n=2
      4), in which each adatom (Cl) has an inclination to be adsorbed at the bridge
      site with electrostatic interaction. Ethylene adsorption over pure and chlorine
      doped FenClm (n,m<=4) clusters is analyzed using density functional theory (DFT)
      calculations, in pi and di-sigma adsorption modes. One of the interesting
      features is that the adsorption mode of ethylene changes by going from trimers to
      tetramers. Ethylene never orients toward di-sigma mode for FeFe bond in Fe2 and
      Fe3 series, while this orientation is preferred in tetramers. Our results
      demonstrate that the progressive change in the ethylene adsorption could not be
      sustained with increasing portion of chlorine in metal cluster. In this study, we
      attempt to provide a sensible justification for this phenomenon by the natural
      bond orbital (NBO) and quantum theory of atoms-in-molecules (QTAIM) analyses.

PMID- 27041446
TI  - In-silico bonding schemes to encode chemical bonds involving sharing of electrons
      in molecular structures.
AB  - Encoding of covalent and coordinate covalent bonds in molecular structures using
      ground state valence electronic configuration is achieved. The bonding due to
      electron sharing in the molecular structures is described with five fundamental
      bonding categories viz. uPair-uPair, lPair-uPair, uPair-lPair, vPair-lPair, and
      lPair-lPair. The involvement of lone pair electrons and the vacant electron
      orbitals in chemical bonding are explained with bonding schemes namely "target
      vacant promotion", "source vacant promotion", "target pairing promotion", "source
      pairing promotion", "source cation promotion", "source pairing double bond",
      "target vacant occupation", and "double pairing promotion" schemes. The bonding
      schemes are verified with a chemical structure editor. The bonding in the
      structures like ylides, PCl5, SF6, IF7, N-Oxides, BF4(-), AlCl4(-) etc. are
      explained and encoded unambiguously. The encoding of bonding in the structures of
      various organic compounds, transition metals compounds, coordination complexes
      and metal carbonyls is accomplished.

PMID- 27041447
TI  - Tautomeric transformation of temozolomide, their proton affinities and chemical
      reactivities: A theoretical approach.
AB  - The gas-phase geometry optimizations of bare, mono- and dihydrated complexes of
      temozolomide isomers were carried out using density functional calculation at the
      M06-2X/6-31+G(d,p) level of the theory. The structures and protonation energies
      of protonated species of temozolomide are reported. Chemical indices of all
      isomers and protonated species are also reported. Energies, thermodynamic
      quantities, rate constants and equilibrium constants of tautomeric and rotameric
      transformations of all isomers I1<->TZM<->HIa<->HIb<->I2<->I3 in bare and
      hydrated systems were obtained.

PMID- 27041448
TI  - Graphene confinement effects on melting/freezing point and structure and dynamics
      behavior of water.
AB  - In this work, the melting/freezing point of confined water between two graphene
      sheets was calculated from the direct coexistence of the solid-liquid interface.
      Also, molecular dynamics simulation of confined liquid water-ice between two
      graphene sheets was applied. The phase transition temperature of the confined ice
      water mixture was calculated as 240K that was 29K less than the non-confined ice
      water system. In order to study the behavior of water molecules at different
      distances from the graphene sheets, 5 regions were provided using some imaginary
      planes, located between two graphene sheets. The obtained simulation results
      showed that water molecules located in the region near each graphene sheet with
      the thickness of 2nm had a different behavior from other water molecules located
      in other regions. The results demonstrated that water molecules in the vicinity
      of graphene sheets had more mean square displacements than those in the middle
      regions.

PMID- 27041449
TI  - Regulation of hepatic energy metabolism by the nuclear receptor PXR.
AB  - The pregnane X receptor (PXR) is a nuclear receptor that is traditionally thought
      to be specialized for sensing xenobiotic exposure. In concurrence with this
      feature PXR was originally identified to regulate drug-metabolizing enzymes and
      transporters. During the last ten years it has become clear that PXR harbors
      broader functions. Evidence obtained both in experimental animals and humans
      indicate that ligand-activated PXR regulates hepatic glucose and lipid metabolism
      and affects whole body metabolic homeostasis. Currently, the consequences of PXR
      activation on overall metabolic health are not yet fully understood and varying
      results on the effect of PXR activation or knockout on metabolic disorders and
      weight gain have been published in mouse models. Rifampicin and St. John's wort,
      the prototypical human PXR agonists, impair glucose tolerance in healthy
      volunteers. Chronic exposure to PXR agonists could potentially represent a risk
      factor for diabetes and metabolic syndrome. This article is part of a Special
      Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited
      by Dr. Wen Xie.

PMID- 27041450
TI  - Rewarming Temperature During Cardiopulmonary Bypass and Acute Kidney Injury: A
      Multicenter Analysis.
AB  - BACKGROUND: Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is
      associated with a requirement for dialysis, a longer stay in the intensive care
      unit, a longer hospital length of stay, and mortality. An oxygenator arterial
      outlet temperature greater than 37 degrees C has been reported to be associated
      with AKI; however, the influence of other rewarming temperatures is unclear.
      Using multicenter registry data, this study aimed to evaluate the role of CPB
      rewarming temperatures on AKI. METHODS: Data from 8,407 adult patients undergoing
      coronary artery bypass grafting (CABG) or valve repair or replacement, or a
      combination, were collected using the Perfusion Downunder Collaborative Database.
      Primary variables of interest were rewarming temperatures, defined as cumulative
      time the oxygenator arterial outlet temperature was greater than 36 degrees C,
      greater than 36.5 degrees C, or greater than 37 degrees C. Propensity scores were
      calculated to determine the predicted probability of hyperthermic perfusion
      (rewarming temperature >37 degrees C). The influence of temperature on AKI was
      determined using separate multivariate models adjusting for propensity score in
      the entire cohort (n = 6,904) and in propensity-matched patients (n = 2,044).
      RESULTS: Overall, 11.8% of patients acquired AKI. The duration of rewarming
      temperature greater than 36 degrees C or 36.5 degrees C was not associated with
      AKI. The duration of rewarming temperature greater than 37 degrees C
      (hyperthermic perfusion) was independently associated with RIFLE (Risk, Injury,
      Failure, Loss, End-stage renal disease) risk classification or greater (odds
      ratio [OR], 1.42; 95% confidence interval [CI], 1.09-1.77; p = 0.012) and injury
      classification or greater AKI (OR, 1.52; 95% CI, 1.09-1.97; p = 0.016) in the
      entire cohort, and injury classification or greater AKI (OR, 1.51; 95% CI, 1.15
      1.90; p = 0.006) in propensity-matched patients. CONCLUSIONS: The duration of
      hyperthermic perfusion-rewarming temperature greater than 37 degrees C-was an
      independent predictor of AKI. Avoidance of hyperthermic perfusion may be more
      beneficial in reducing AKI than avoidance of rewarming.

PMID- 27041451
TI  - The Society of Thoracic Surgeons General Thoracic Surgery Database Update on
      Outcomes and Quality.
AB  - The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) is
      a voluntary effort that provides participants with semiannual, risk-adjusted
      performance reports that facilitate quality improvement and comparison of
      institutional outcomes with national benchmarks. With improved participation in
      the STS GTSD, increasingly meaningful analyses are available. This year, risk
      models for lobectomy and esophagectomy for cancer were updated. In addition, we
      developed the first composite quality measure for general thoracic surgery, a
      composite measure for lobectomy for lung cancer. Furthermore, international
      collaboration with the European Society of Thoracic Surgery has facilitated our
      understanding of variation between American and European treatment patterns,
      providing a foundation for future quality improvement initiatives. This article
      summarizes current aggregate national outcomes in general thoracic surgery and
      reviews related activities in the areas of quality measurement, performance
      improvement, and transparency from the STS GTSD over the past 12 months. 

PMID- 27041452
TI  - The Natural History of Operable Non-Small Cell Lung Cancer in the National Cancer
      Database.
AB  - BACKGROUND: The survival of untreated non-small cell lung cancer (NSCLC), or the
      natural history, is an important perspective for patients considering resection
      for NSCLC. The National Cancer Database (NCDB) allows untreated NSCLC patients
      who were recommended to undergo surgical resection (ie, "operable") to be
      identified. The survival of untreated NSCLC patients in the NCDB was studied to
      determine the natural history of operable NSCLC. METHODS: The NCDB was queried
      for untreated clinical stage I to IIIA NSCLC patients diagnosed between 2003 and
      2009. The natural history cohort was defined as patients who were recommended to
      undergo resection but went untreated. RESULTS: We identified 1,693 untreated
      patients with operable NSCLC. The median survival for clinical stage I, II, and
      IIIA was 16.6, 9.4, and 8.4 months, respectively. The 5-year Kaplan-Meier
      estimates of survival for clinical stage I, II, and IIIA NSCLC were 10.1%, 7.3%,
      and 4.9%, respectively. At each stage (I to IIIA), the survival of untreated
      operable NSCLC patients was superior to that of untreated NSCLC patients not
      recommended to undergo resection (nonoperable, p < 0.001). A multivariable Cox
      regression model identified increasing age, male gender, white (vs black) race,
      increasing comorbidity, squamous cell or large cell histology, and increasing
      stage as predictors of decreased survival. CONCLUSIONS: The natural history of
      operable NSCLC, although poor, varies with clinical stage and is superior to that
      of nonoperable NSCLC.

PMID- 27041453
TI  - Minimally Invasive Mitral Valve Surgery Provides Excellent Outcomes Without
      Increased Cost: A Multi-Institutional Analysis.
AB  - BACKGROUND: Minimally invasive mitral valve surgery (mini-MVR) has grown in
      popularity. Although single centers have reported excellent outcomes, data on
      real-world outcomes and costs of mini-MVR are limited. Moreover, mini-MVR has
      been criticized as adding additional cost without clear benefit. We hypothesized
      that mini-MVR provides superior outcomes with incremental increased costs in a
      multi-institutional cohort. METHODS: Records for patients undergoing mitral valve
      surgical procedures with or without atrial ablation from 2011 to 2014 were
      extracted from a multi-institutional, regional Society of Thoracic Surgeons
      database and stratified according to right chest approach/minimally invasive or
      conventional sternotomy. Patients undergoing coronary artery bypass grafting or
      other concomitant procedures were excluded. Patients undergoing isolated mitral
      surgical procedure were propensity matched according to factors, including age,
      comorbidities, and preoperative laboratory values; clinical outcomes and cost
      differences were assessed by approach. RESULTS: A total of 1,304 patients
      underwent mitral operations, including 425 (32.6%) by minimally invasive
      approach. In the propensity-matched analysis (n = 355 per group), patients
      undergoing mini-MVR had similar rates of mortality, stroke, and other
      complications compared with conventional MVR. Meanwhile, patients with mini-MVR
      experienced shorter intensive care unit and hospital lengths of stay and fewer
      transfusions. Importantly, total hospital costs were no different between the two
      matched groups. CONCLUSIONS: Compared with conventional sternotomy, mini-MVR in
      the "real world" demonstrated no differences in rates of major morbidity, but it
      was associated with shorter length of stay and fewer transfusions. Contrary to
      our hypothesis, mini-MVR can be performed with similar total hospital costs as
      conventional sternotomy. In summary, minimally invasive mitral surgical procedure
      in select patients can provide superior outcomes without increased cost.

PMID- 27041454
TI  - The Impact of Delirium After Cardiac Surgical Procedures on Postoperative
      Resource Use.
AB  - BACKGROUND: Delirium is a common complication after cardiac surgical procedures
      and is associated with increased morbidity and mortality. However, whether
      rigorously assessed postoperative delirium is associated with an increased length
      of stay in the intensive care unit (LOS-ICU), length of stay (LOS), and hospital
      charges is not clear. METHODS: Patients (n = 66) undergoing coronary artery
      bypass or valve operations, or both, were enrolled in a nested cohort study.
      Rigorous delirium assessments were conducted using the Confusion Assessment
      Method. LOS-ICU and LOS were obtained from the medical record, and hospital
      charges were obtained from administrative data reported to the state. Because of
      the skewed distribution of outcome variables, outcomes were compared using rank
      sum tests, as well as median regression incorporating propensity scores. RESULTS:
      Patients who developed delirium (56%) versus no delirium (43%) had increased
      median LOS-ICU (75.6 hours [interquartile range (IQR): 43.6 to 136.8] vs. 29.7
      hours [IQR: 21.7 to 46.0]; p = 0.002), increased median LOS (9 days [IQR: 6 to
      16] vs. 7 days [IQR: 5 to 8]; p = 0.006), and increased median hospital charges
      ($51,805 [IQR: $44,041 to $80,238] vs. $41,576 [IQR: $35,748 to $43,660]; p =
      0.002). In propensity score models adjusted for patient-related and surgical
      characteristics and complications, the results for LOS-ICU and cost remained
      highly significant, although the results for LOS were attenuated on the basis of
      the specific statistical model. Increased severity of delirium was associated
      with both increased LOS-ICU and increased charges in a dose-response manner.
      CONCLUSIONS: Delirium after cardiac surgical procedures is independently
      associated with both increased LOS-ICU and higher hospital charges. Because
      delirium is potentially preventable, targeted delirium-prevention protocols for
      high-risk patients may represent an important strategy for quality improvement.

PMID- 27041455
TI  - Ross Versus Non-Ross Aortic Valve Replacement in Children: A 22-Year Single
      Institution Comparison of Outcomes.
AB  - BACKGROUND: The Ross aortic valve replacement (AVR) has been the AVR of choice
      for children at our center since 1993. Absence or inadequate quality of the
      pulmonary valve or, less commonly, family or surgeon preference caused us to
      select an alternative AVR prosthesis for some children. This review compares the
      outcomes of 42 children who received a non-Ross AVR with 115 children undergoing
      Ross root replacement at our institution during the most recent 22 years.
      METHODS: A retrospective chart review of the 42 pediatric non-Ross AVRs was
      compared with 115 Ross AVRs. The mean age at AVR was 11.0 +/- 6.5 years (range, 1
      month to 18 years) for the non-Ross and 11.4 +/- 5.5 years (range, 6 weeks to 18
      years) for the Ross groups. Follow-up was 7.8 +/- 6.2 years for the Ross group
      and 8.7 +/- 6.5 years for the non-Ross group. The Ross AVR technique was modified
      in 2000; these modifications were applied to 72 patients (63%) of the total Ross
      AVR group. RESULTS: All-cause early and late mortality of the non-Ross AVR group
      was 17% compared with 4% for the Ross cohort (p = 0.017). The actuarial survival
      rate at 20 years for the non-Ross AVR group was 81% compared with 94% for the
      Ross group (p = 0.018). Reintervention rate was 29% (12/38) in the non-Ross group
      and 28% (32/115) in the entire Ross group (60% [26/43] before 2000, and 8% [6/72]
      after 2000). Thromboemboli, bleeding, and endocarditis occurred in 2.4%, 1.4%,
      and 10% in the non-Ross group compared with 0.9%, 2.6%, and 1.7% in the Ross AVR
      group (p = 0.46, 0.01, and 0.02), respectively. Patients in the non-Ross group
      had a significantly higher recurrent or persistent aortic valve gradient (>20 mm
      Hg) than did patients in the Ross group at most recent follow-up (p < 0.05).
      CONCLUSIONS: Lower mortality, valve-related complications, and better
      hemodynamics were seen after the Ross AVR than with other types of AVR
      prostheses. The Ross AVR remains the treatment of choice for children who have an
      adequate pulmonary valve. Reoperation for Ross root dilatation, regurgitation, or
      both (only 6% since our modifications in 2000) has markedly reduced the main
      drawbacks of this AVR technique. The Ross AVR affords the growing child the
      advantages of a growing, autologous, viable valve substitute and eliminates the
      lifelong disadvantages of mechanical and xenograft valves.

PMID- 27041456
TI  - A study of the properties of chlorine dioxide gas as a fumigant.
AB  - Chlorine dioxide (ClO2) is a strong oxidant that possesses an antimicrobial
      activity. We demonstrated here that ClO2 gas is easily generated by mixing 3.35%
      sodium chlorite solution (Purogene) and 85% phosphoric acid at a 10:1 volume
      ratio without using an expensive machine. In a test room (87 m(3)), experiments
      were carried out using various amounts of sodium chlorite solution (0.25 ml/m(3)
      to 20.0 ml/m(3)). The gas concentration increased in a sodium chlorite volume
      dependent manner and reached peak values of from 0.8 ppm to 40.8 ppm at 2 h-3 h,
      and then gradually decreased. No differences in gas concentrations were observed
      between 0.1 and 2.5 m above the floor, indicating that the gas was evenly
      distributed. Under high-humidity (approximately 80% relative humidity), colony
      formation of both Staphylococcus aureus and Escherichia coli was completely
      inhibited by ClO2 gas exposure at 1.0 ml/m(3) sodium chlorite solution (mean
      maximal concentration of 3.0 ppm). Exposure at 4.0 ml/m(3) sodium chlorite
      solution (mean maximal concentration of 10.6 ppm) achieved complete inactivation
      of Bacillus atrophaeus spores. In contrast, without humidification, the efficacy
      of ClO2 gas was apparently attenuated, suggesting that the atmospheric moisture
      is indispensable. Delicate electronic devices (computer, camera, etc.) operated
      normally, even after being subjected to more than 20 times of fumigation.
      Considering that our method for gas generation is simple, reproducible, and
      highly effective at decontaminating microbes, our approach is expected to serve
      as an inexpensive alternative method for cleaning and disinfecting animal
      facilities. 

PMID- 27041457
TI  - Establishment of an intermittent cold stress model using Tupaia belangeri and
      evaluation of compound C737 targeting neuron-restrictive silencer factor.
AB  - Previous studies have shown that intermittent cold stress (ICS) induces
      depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the
      only experimental animal other than the chimpanzee that has been shown to be
      susceptible to infection by hepatitis B and C viruses. Moreover, full genome
      sequence analysis has revealed strong homology between host proteins in Tupaia
      and in humans and other primates. Tupaia neuromodulator receptor proteins are
      also known to have a high degree of homology with their corresponding primate
      proteins. Based on these similarities, we hypothesized that induction of ICS in
      Tupaia would provide a useful animal model of stress responses. We exposed young
      adult Tupaia to ICS and observed decreases in body temperature and body weight in
      both female and male Tupaia, suggesting that Tupaia are an appropriate animal
      model for ICS studies. We further examined the efficacy of a new small-molecule
      compound, C737, against the effects of ICS. C737 mimics the helical structure of
      neuron-restrictive silencer factor (NRSF/REST), which regulates a wide range of
      target genes involved in neuronal function and pain modulation. Treatment with
      C737 significantly reduced stress-induced weight loss in female Tupaia; these
      effects were stronger than those elicited by the antidepressant agomelatine.
      These results suggest that Tupaia represents a useful non-rodent ICS model. Our
      data also provide new insights into the function of NRSF/REST in stress-induced
      depression and other disorders with epigenetic influences or those with high
      prevalence in women. 

PMID- 27041458
TI  - Autophagy activation prevents sevoflurane-induced neurotoxicity in H4 human
      neuroglioma cells.
AB  - AIM: The inhaled anesthetic sevoflurane may induce cognitive impairment in both
      animals and humans. Previous study has shown that sevoflurane triggers ER stress
      and may lead to apoptosis in rat hippocampal neurons. In this study, we examined
      whether sevoflurane caused autophagy and its contributions to sevoflurane induced
      neuronal cell injury. METHODS: H4 human neuroglioma cells were exposed to 4.1%
      sevoflurane for 6 h. Cell viability and apoptosis ratio were assessed using a
      CCK8 kit and flow cytometry, respectively. Autophagosomes in the cells were
      detected using GFP-LC3 plasmid transfection or transmission electronic
      microscopy. The expression of LC3B, p62/SQSTM, C/EBP homologous protein (CHOP)
      and glucose-related protein 78 (GRP78) was assessed with Western blotting.
      RESULTS: Sevoflurane treatment induced apoptosis and markedly increased the LC3
      II level and GFP-LC3 puncta number, decreased p62 expression in H4 cells.
      Activation of autophagy by rapamycin (1 MUmol/L) significantly reduced
      sevoflurane-induced apoptosis and increased cell viability, whereas inhibition of
      autophagy with 3-MA (5 mmol/L) caused the opposite effects. Furthermore,
      sevoflurane treatment markedly increased the expression of CHOP and GRP78, two
      hallmark proteins of ER stress. Inhibition of ER stress by 4-phenylbutyrate (500
      MUmol/L) abrogated sevoflurane-induced autophagy and apoptosis, and improved the
      viability. Moreover, sevoflurane-stimulated expression of CHOP and GRP78 was
      inhibited by rapamycin, but further enhanced by 3-MA. CONCLUSION: Sevoflurane
      treatment induces ER stress and activates autophagy, which antagonizes
      sevoflurane-induced apoptosis in H4 human neuroglioma cells. The results suggest
      that autophagy may be a potential therapeutic target in preventing sevoflurane
      induced neurotoxicity.

PMID- 27041459
TI  - DL0805-2, a novel indazole derivative, relaxes angiotensin II-induced
      contractions of rat aortic rings by inhibiting Rho kinase and calcium fluxes.
AB  - AIM: DL0805-2 [N-(1H-indazol-5-yl)-1-(4-methylbenzyl) pyrrolidine-3-carboxamide]
      is a DL0805 derivative with more potent vasorelaxant activity and lower toxicity.
      This study was conducted to investigate the vasorelaxant mechanisms of DL0805-2
      on angiotensin II (Ang II)-induced contractions of rat thoracic aortic rings in
      vitro. METHODS: Rat thoracic aortic rings and rat aortic vascular smooth muscle
      cells (VSMCs) were pretreated with DL0805-2, and then stimulated with Ang II. The
      tension of the aortic rings was measured through an isometric force transducer.
      Ang II-induced protein phosphorylation, ROS production and F-actin formation were
      assessed with Western blotting and immunofluorescence assays. Intracellular free
      Ca(2+) concentrations were detected with Fluo-3 AM. RESULTS: Pretreatment with
      DL0805-2 (1-100 MUmol/L) dose-dependently inhibited the constrictions of the
      aortic rings induced by a single dose of Ang II (10(-7) mol/L) or accumulative
      addition of Ang II (10(-10)-10(-7) mol/L). The vasodilatory effect of DL0805-2
      was independent of endothelium. In the aortic rings, pretreatment with DL0805-2
      (1, 3, and 10 MUmol/L) suppressed Ang II-induced Ca(2+) influx and intracellular
      Ca(2+) mobilization, and Ang II-induced phosphorylation of two substrates of Rho
      kinase (MLC and MYPT1). In VSMCs, pretreatment with DL0805-2 (1, 3, and 10
      MUmol/L) also suppressed Ang II-induced Ca(2+) fluxes and phosphorylation of MLC
      and MYPT1. In addition, pretreatment with DL0805-2 attenuated ROS production and
      F-actin formation in the cells. CONCLUSION: DL0805-2 exerts a vasodilatory action
      in rat aortic rings through inhibiting the Rho/ROCK pathway and calcium fluxes.

PMID- 27041460
TI  - Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated
      human fibroblast-like synoviocytes in vitro and in mice with collagen-induced
      arthritis.
AB  - AIM: Hyperoside is a flavonol glycoside mainly found in plants of the genera
      Hypericum and Crataegus, which has shown anti-oxidant, anti-cancer and anti
      inflammatory activities. In this study, we investigated the effects of hyperoside
      on human rheumatoid fibroblast-like synoviocytes (FLSs) in vitro and on mouse
      collagen-induced arthritis (CIA) in vivo. METHODS: FLSs were isolated from
      primary synovial tissues obtained from rheumatoid arthritis (RA) patients and
      exposed to LPS (1 MUg/mL). Cell viability and proliferation were measured with
      MTT and BrdU assay. Cell migration was assessed using wound-healing assay and
      Transwell assay. DNA binding of NF-kappaB was measured using a TransAM-NFkappaB
      kit. The localization of p65 subunit was detected with immunocytochemistry. CIA
      was induced in mice by primary immunization with Bovine Type II collagen (CII)
      emulsified in CFA, followed by a booster injection 3 weeks later. The arthritic
      mice were treated with hyperoside (25, 50 mg.kg(-1).d(-1), ip) for 3 weeks, and
      the joint tissues were harvested for histological analysis. RESULTS: Hyperoside
      (10, 50, 100 MUmol/L) dose-dependently inhibited LPS-induced proliferation and
      migration of human RA FLSs in vitro. Furthermore, hyperoside decreased LPS
      stimulated production of TNF-alpha, IL-6, IL-1 and MMP-9 in the cells. Moreover,
      hyperoside inhibited LPS-induced phosphorylation of p65 and IkappaBalpha, and
      suppressed LPS-induced nuclear translocation of p65 and DNA biding of NF-kappaB
      in the cells. Three-week administration of hyperoside significantly decreased the
      clinical scores, and alleviated synovial hyperplasia, inflammatory cell
      infiltration and cartilage damage in mice with CIA. CONCLUSION: Hyperoside
      inhibits LPS-induced proliferation, migration and inflammatory responses in human
      RA FLSs in vitro by suppressing activation of the NF-kappaB signaling pathway,
      which contributes to the therapeutic effects observed in mice with CIA.

PMID- 27041461
TI  - Activation of p53 contributes to pseudolaric acid B-induced senescence in human
      lung cancer cells in vitro.
AB  - AIM: Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of
      Pseudolarix kaempferi Gordon, has shown to exert anti-tumor effects via inducing
      cell cycle arrest followed by apoptosis in several cancer cell lines. Here we
      reported that PAB induced a mitotic catastrophe in human lung cancer A549 cells,
      which resulted in senescence without apoptosis or necrosis. METHODS: Three human
      lung cancer cell lines (A549, H460 and H1299 cells) were examined. Cell growth
      inhibition was assessed with MTT assay. Cell cycle distribution was determined
      using a flow cytometer. Cell nuclear morphology was observed under a fluorescence
      microscope. Senescent cells were detected using SA-beta-Gal staining. Apoptotic
      and senescent protein expression was examined using Western blot analysis. The
      expression of p53 and p21 in the cells was downregulated by siRNAs. RESULTS:
      Treatment with PAB (5-80 MUmol/L) inhibited the growth of A549 cells in dose- and
      time-dependent manners. Prolonged treatment with PAB (20 MUmol/L) caused G2/M
      arrest at day 1 followed by mitotic catastrophe from day 2, which eventually
      resulted in cell senescence between days 3 and 4 without cell death (apoptosis or
      necrosis). Knockdown of p53 expression with siRNA significantly suppressed PAB
      induced senescence in A549 cells (p53 wild). Furthermore, PAB-induced senescence
      was also observed in human lung cancer H460 cells (p53 wild), but not in human
      lung cancer H1299 cells (p53 null). CONCLUSION: The anti-tumor action of PAB
      against human lung cancer A549 cells in vitro involves the induction of
      senescence through activation of the p53 pathway.

PMID- 27041462
TI  - Discovery of a new series of imidazo[1,2-a]pyridine compounds as selective c-Met
      inhibitors.
AB  - AIM: Aberrant c-Met activation plays a critical role in cancer formation,
      progression and dissemination, as well as in development of resistance to
      anticancer drugs. Therefore, c-Met has emerged as an attractive target for cancer
      therapy. The aim of this study was to develop new c-Met inhibitors and elaborate
      the structure-activity relationships of identified inhibitors. METHODS: Based on
      the predicted binding modes of Compounds 5 and 14 in docking studies, a new
      series of c-Met inhibitor-harboring 3-((1H-pyrrolo[3,2-c]pyridin-1
      yl)sulfonyl)imidazo[1,2-a]pyridine scaffolds was discovered. Potent inhibitors
      were identified through extensive optimizations combined with enzymatic and
      cellular assays. A promising compound was further investigated in regard to its
      selectivity, its effects on c-Met signaling, cell proliferation and cell
      scattering in vitro. RESULTS: The most potent Compound 31 inhibited c-Met kinase
      activity with an IC50 value of 12.8 nmol/L, which was >78-fold higher than those
      of a panel of 16 different tyrosine kinases. Compound 31 (8, 40, 200 nmol/L) dose
      dependently inhibited the phosphorylation of c-Met and its key downstream Akt and
      ERK signaling cascades in c-Met aberrant human EBC-1 cancer cells. In 12 human
      cancer cell lines harboring different background levels of c-Met
      expression/activation, Compound 31 potently inhibited c-Met-driven cell
      proliferation. Furthermore, Compound 31 dose-dependently impaired c-Met-mediated
      cell scattering of MDCK cells. CONCLUSION: This series of c-Met inhibitors is a
      promising lead for development of novel anticancer drugs.

PMID- 27041463
TI  - Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro
      by inhibiting the p53-dependent mitochondrial apoptotic pathway.
AB  - AIM: Intra-articular injection of local anesthetics (LAs) is a common procedure
      for therapeutic purposes. However, LAs have been found toxic to articular
      cartilage, and hyaluronan may attenuate this toxicity. In this study we
      investigated whether hyaluronan attenuated lidocaine-induced chondrotoxicity, and
      if so, to elucidate the underlying mechanisms. METHODS: Human chondrocyte cell
      line SW1353 and newly isolated murine chondrocytes were incubated in culture
      medium containing hyaluronan and/or lidocaine for 72 h. Cell viability was
      evaluated using MTT assay. Cell apoptosis was detected with DAPI staining,
      caspase 3/7 activity assay and flow cytometry. Cell cycle distributions, ROS
      levels and mitochondrial membrane potential (DeltaPsim) were determined using
      flow cytometry. The expression of p53 and p53-regulated gene products was
      measured with Western blotting. RESULTS: Lidocaine (0.005%-0.03%) dose
      dependently decreased the viability of SW1353 cells. This local anesthetic
      (0.015%, 0.025%) induced apoptosis, G2/M phase arrest and loss of DeltaPsim, and
      markedly increased ROS production in SW1353 cells. Hyaluronan (50-800 MUg/mL)
      alone did not affect the cell viability, but co-treatment with hyaluronan (200
      MUg/mL) significantly attenuated lidocaine-induced apoptosis and other
      abnormalities in SW1353 cells. Furthermore, co-treatment with lidocaine and
      hyaluronan significantly decreased the levels of p53 and its transcription
      targets Bax and p21 in SW1353 cells, although treatment with lidocaine alone did
      not significantly change these proteins. Similar results were obtained in ex vivo
      cultured murine chondrocytes. CONCLUSION: Hyaluronan suppresses lidocaine-induced
      apoptosis of human chondrocytes in vitro through inhibiting the p53-dependent
      mitochondrial apoptotic pathway.

PMID- 27041464
TI  - N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse
      obstructed kidneys.
AB  - AIM: To investigate the effects of ROS scavenger N-acetylcysteine (NAC) on
      angiotensin II (Ang II)-mediated renal fibrosis in vivo and in vitro. METHODS:
      Mice were subjected to unilateral ureteral obstruction (UUO), and then treated
      with vehicle or NAC (250 mg/kg, ip) for 7 days. Histological changes of the
      obstructed kidneys were observed with Masson's trichrome staining. ROS levels
      were detected with DHE staining. The expression of relevant proteins in the
      obstructed kidneys was assessed using Western blotting assays. Cultured rat renal
      fibroblast NRK-49F cells were used for in vitro experiments. RESULTS: In the
      obstructed kidneys, Ang II levels were significantly elevated, and collagen I was
      accumulated in the interstitial spaces. Furthermore, ROS production and the
      expression of p47 (a key subunit of NADPH oxidase complexes) were increased in a
      time-dependent manner; the expression of fibronectin, alpha-SMA and TGF-beta were
      upregulated. Administration of NAC significantly alleviated the fibrotic
      responses in the obstructed kidneys. In cultured NRK-49F cells, treatment with
      Ang II (0.001-10 MUmol/L) increased the expression of fibronectin, collagen I,
      alpha-SMA and TGF-beta in dose-dependent and time-dependent manners. Ang II also
      increased ROS production and the phosphorylation of Smad3. Pretreatment with NAC
      (5 MUmol/L) blocked Ang II-induced oxidative stress and ECM production in the
      cells. CONCLUSION: In mouse obstructed kidneys, the fibrotic responses result
      from Ang II upregulation can be alleviated by the ROS scavenger N-acetylcysteine.

PMID- 27041465
TI  - [Cauda equina syndrome after chiropractic treatment].

PMID- 27041466
TI  - Development of the Tool to Reduce Inappropriate Medications (TRIM): A Clinical
      Decision Support System to Improve Medication Prescribing for Older Adults.
AB  - STUDY OBJECTIVE: To create a clinical decision support system (CDSS) for
      evaluating problems with medications among older outpatients based on a broad set
      of criteria. DESIGN: Web-based CDSS development. SETTING: Primary care clinics at
      a Veterans Affairs medical center. PARTICIPANTS: Forty veterans 65 years and
      older who were prescribed seven or more medications that included those for
      treatment of diabetes mellitus and hypertension. MEASUREMENTS AND MAIN RESULTS:
      The Tool to Reduce Inappropriate Medications (TRIM) uses a program to extract
      age, medications, and chronic conditions from the electronic health record to
      identify high-risk patients and as input for evaluating the medication regimen.
      Additional health variables obtained through chart review and direct patient
      assessment are entered into a Web-based program. Based on a series of algorithms,
      TRIM generates feedback reports for clinicians. TRIM identified medication
      reconciliation discrepancies in 98% (39/40) of veterans, potentially
      inappropriate medications in 58% (23/40), potential problems with feasibility
      (based on poor adherence and/or cognitive impairment) in 25% (10/40), potential
      overtreatment of hypertension in 50% (20/40), potential overtreatment of diabetes
      in 43% (17/40), inappropriate dosing of renally excreted medications in 5%
      (2/40), and patient-reported adverse reactions in 5% (2/40). CONCLUSION: This
      evaluation of TRIM demonstrated that data elements can be extracted from the
      electronic health record to identify older primary care patients at risk for
      potentially problematic medication regimens. Supplemented with chart review and
      direct patient assessment, these data can be processed through clinical
      algorithms that identify potential problems and generate patient-specific
      feedback reports. Additional work is necessary to assess the effects of TRIM on
      medication deprescribing.

PMID- 27041467
TI  - Control of the collective migration of enteric neural crest cells by the
      Complement anaphylatoxin C3a and N-cadherin.
AB  - We analyzed the cellular and molecular mechanisms governing the adhesive and
      migratory behavior of enteric neural crest cells (ENCCs) during their collective
      migration within the developing mouse gut. We aimed to decipher the role of the
      complement anaphylatoxin C3a during this process, because this well-known immune
      system attractant has been implicated in cephalic NCC co-attraction, a process
      controlling directional migration. We used the conditional Ht-PA-cre transgenic
      mouse model allowing a specific ablation of the N-cadherin gene and the
      expression of a fluorescent reporter in migratory ENCCs without affecting the
      central nervous system. We performed time-lapse videomicroscopy of ENCCs from
      control and N-cadherin mutant gut explants cultured on fibronectin (FN) and
      micropatterned FN-stripes with C3a or C3aR antagonist, and studied cell migration
      behavior with the use of triangulation analysis to quantify cell dispersion. We
      performed ex vivo gut cultures with or without C3aR antagonist to determine the
      effect on ENCC behavior. Confocal microscopy was used to analyze the cell-matrix
      adhesion properties. We provide the first demonstration of the localization of
      the complement anaphylatoxin C3a and its receptor on ENCCs during their migration
      in the embryonic gut. C3aR receptor inhibition alters ENCC adhesion and
      migration, perturbing directionality and increasing cell dispersion both in vitro
      and ex vivo. N-cadherin-null ENCCs do not respond to C3a co-attraction. These
      findings indicate that C3a regulates cell migration in a N-cadherin-dependent
      process. Our results shed light on the role of C3a in regulating collective and
      directional cell migration, and in ganglia network organization during enteric
      nervous system ontogenesis. The detection of an immune system chemokine in ENCCs
      during ENS development may also shed light on new mechanisms for gastrointestinal
      disorders.

PMID- 27041468
TI  - Enhancement of biodegradation and osseointegration of poly(epsilon
      caprolactone)/calcium phosphate ceramic composite screws for osteofixation using
      calcium sulfate.
AB  - Internal fixation devices, which can stabilize and realign fractured bone, are
      widely used in fracture management. In this paper, a biodegradable composite
      fixator, composed of poly(epsilon-caprolactone), calcium phosphate ceramic and
      calcium sulfate (PCL/CPC/CS), is developed. The composition of CS, which has a
      high dissolution rate, was expected to create a porous structure to improve
      osteofixation to the composite fixator. PCL, PCL/CPC, and PCL/CPC/CS samples were
      prepared and their physical properties were characterized in vitro. In vivo
      performance of the composite screws was verified in the distal femurs of rabbits.
      Results showed that the PCL/CPC/CS composite had a higher compressive strength
      (28.55 +/- 3.32 MPa) in comparison with that of PCL (20.64 +/- 1.81 MPa) (p <
      0.05). A larger amount of apatite was formed on PCL/CPC/CS than on PCL/CPC, while
      no apatite was found on PCL after simulated body fluid immersion. In addition,
      PCL/CPC/CS composites also had a faster in vitro degradation rate (13.05 +/-
      3.42% in weight loss) relative to PCL (1.79 +/- 0.23%) and PCL/CPC (4.32 +/-
      2.18%) (p < 0.001). In animal studies, PCL/CPC/CS screws showed a greater volume
      loss than that of PCL or PCL/CPC at 24 weeks post-implantation. Under micro
      computerized tomography observation, animals with PCL/CPC/CS implants had better
      osseointegration in terms of the structural parameters of the distal metaphysis,
      including trabecular number, trabecular spacing, and connectivity density, than
      the PCL screw. This study reveals that the addition of CS accelerates the
      biodegradation and enhanced apatite formation of the PCL/CPC composite screw.
      This osteoconductive PCL/CPC/CS is a good candidate material for internal
      fixation devices.

PMID- 27041469
TI  - Change in Management Based on Pathologic Second Opinion Among Bladder Cancer
      Patients Presenting to a Comprehensive Cancer Center: Implications for Clinical
      Practice.
AB  - OBJECTIVE: To evaluate the incidence and degree of change from a pathologic
      second opinion of bladder biopsies at a Comprehensive Cancer Center that were
      initially performed at referring community hospitals. The secondary objective was
      to determine the impact the potential changes would have on a patient's
      treatment. MATERIALS AND METHODS: Dedicated genitourinary pathologists reviewed
      1191 transurethral biopsies of the bladder and/or prostatic urethra from 2008 to
      2013. Major and minor treatment changes were defined as altering recommendations
      for cystectomy, systemic chemotherapy, or primary cancer diagnosis, and
      alterations in intravesical regimens, respectively. RESULTS: There were 326/1191
      patients (27.4%) with a pathologic change on second opinion: grade (62/1191,
      5.2%), stage (115/1191, 9.7%), muscle in the specimen (29/1191, 2.4%), presence
      or absence of carcinoma in situ (34/1191, 2.9%). Outside pathology did not
      address the presence or absence of lymphovascular invasion in 620/759 (81.7%) of
      invasive cases (>=cT1), of which 35/620 (5.6%) had lymphovascular invasion. There
      were 212 mixed, variant, or nonurothelial histologies detected in 199/1191
      (16.7%) patients, with 114/212 (53.7%) resulting in reclassification by our
      pathologists. Potential treatment alterations accounted for 182/1191 (15.3%) of
      cases, with 141/1191 (11.8%) imparting major changes. There were 82/1191 (6.8%)
      changes in recommendation for a radical cystectomy, 38/1191 (3.2%) had a complete
      change in primary tumor type, and 21/1191 (1.8%) for change in chemotherapy
      regimen. CONCLUSION: The amount and degree of pathologic changes and its
      potential impact on treatment emphasize the importance of bladder cancer patients
      having their histology reviewed by genitourinary-dedicated pathologists. In our
      cohort, 15.3% of patients could see a treatment alteration, with 11.8% being a
      major change.

PMID- 27041470
TI  - Radiographic Kinetics of Sarcomatoid Renal Cell Carcinoma.
AB  - Renal cell carcinoma is a common entity often managed surgically with excellent
      survival benefits. We report a rare case of sarcomatoid renal cell carcinoma with
      aggressive growth kinetics after palliative resection captured radiographically. 

PMID- 27041471
TI  - Pathological Upstaging of Clinical T1 to Pathological T3a Renal Cell Carcinoma: A
      Multi-institutional Analysis of Short-term Outcomes.
AB  - OBJECTIVE: To determine the oncological impact of pathological upstaging among
      patients with clinical T1 (cT1) disease treated by partial nephrectomy or radical
      nephrectomy. METHODS: The Canadian Kidney Cancer Information System comprises a
      prospectively maintained multi-institutional database for patients with renal
      cell carcinoma. Nonmetastatic, cT1 renal cell carcinoma cases were evaluated.
      Upstaging was defined as pathological T3a disease. Multivariate Cox regression
      analysis identified predictors for recurrence (local recurrence and/or metastatic
      disease) whereas logistic regression identified predictors of pathological
      upstaging. Kaplan-Meier methods estimated survival. RESULTS: Of 1448 eligible cT1
      patients, upstaging was observed in 134 (9%). One thousand fifty-eight (73%) were
      treated by partial nephrectomy. After a median follow-up of 23 months, the 3-year
      recurrence-free survival was 76% in upstaged patients compared with 93% in those
      not upstaged (P < .001). Controlling for age, gender, year of surgery, histology,
      tumor size, surgical approach, and margin status, pathological upstaging was
      independently associated with disease recurrence (hazard ratio 2.03, 95%
      confidence interval [CI] 1.12-3.68). Increasing age (odds ratio [OR] 1.02, 95% CI
      1.00-1.05), Fuhrman grade (OR 2.47, 95% CI 1.47-4.14), and tumor size (OR 1.16,
      95% CI 1.00-1.36) were independently associated with a risk of pathological
      upstaging. CONCLUSION: Pathological upstaging confers a negative prognosis and
      highlights the importance of accurate clinical staging. A number of factors have
      been identified, including some attainable by renal biopsy, which may predict
      upstaging and provide valuable adjunct information to inform risk stratification
      and management decisions among patients with cT1 renal masses.

PMID- 27041472
TI  - Factors Associated With Preventive Pharmacological Therapy Adherence Among
      Patients With Kidney Stones.
AB  - OBJECTIVE: To determine adherence patterns for thiazide diuretics, alkali citrate
      therapy, and allopurinol, collectively referred to as preventive pharmacological
      therapy (PPT), among patients with kidney stones. METHODS: Using medical claims
      data, we identified adults diagnosed with kidney stones between 2002 and 2006.
      Through National Drug Codes, we determined those with one or more prescription
      fills for a PPT agent. We measured adherence to PPT (as determined by the
      proportion of days covered formula) within the first 6 months of starting therapy
      and performed multivariate analysis to evaluate patient factors associated with
      PPT adherence. RESULTS: Among 7980 adults with kidney stones who were prescribed
      PPT, less than one third (30.2%) were adherent to their regimen (indicated by
      proportion of days covered  >= 80%). Among those on monotherapy, rates of
      adherence differed by the type of PPT agent prescribed: 42.5% for thiazides,
      40.0% for allopurinol, and 13.4% for citrate therapy. Factors that were
      independently associated with lower odds of PPT adherence included combination
      therapy receipt, female gender, less generous health insurance, and residence in
      the South or Northeast. In contrast, older patients and those with salaried
      employment had a higher probability of PPT adherence. CONCLUSION: Adherence to
      PPT is low. These findings help providers identify patients where PPT adherence
      will be problematic. Moreover, they suggest possible targets for quality
      improvement efforts in the secondary prevention of kidney stones.

PMID- 27041473
TI  - A New Modification of the Koyanagi Technique for the One-stage Repair of Severe
      Hypospadias.
AB  - OBJECTIVE: To describe a new modification of the Koyanagi technique for the one
      stage repair of severe hypospadias and its short-term outcomes. PATIENTS AND
      METHODS: Our modified Koyanagi technique was performed in 24 patients with severe
      hypospadias between February 2012 and January 2015. The age of the patients
      ranged from 1.9 to 11.9 years (mean = 3.5 years). The flap design was similar to
      the Koyanagi technique, but our modified technique highlighted the following
      points: after the chordee was completely corrected, the urethral plate was
      recreated using foreskin, and then a U-shaped incision was made on the original
      and recreated urethral plate (as in the Duplay technique); a pedicled flap of the
      tunica vaginalis or scrotal dartos was used for additional coverage of the
      neourethra. RESULTS: The operation time lasted from 120 to 150 minutes (mean =
      140 minutes). There were 5 patients (20.8%) who developed complications: 4
      patients (16.7%) developed a fistula and 1 patient (4.2%) developed dehiscence of
      the urethra. There were no reported urethral strictures, meatal stenosis, or
      urethral diverticula. The complications in the 5 patients were successfully
      addressed with secondary repair, and all patients achieved satisfactory cosmetic
      and urethral functional results. CONCLUSION: The modified Koyanagi technique
      simplified the operation and better preserved the blood supply to the flap. The
      additional coverage of the neourethra using a pedicled flap of the tunica
      vaginalis or scrotal dartos significantly decreased the rate of fistula
      formation. This technique is highly suitable for the one-stage repair of severe
      hypospadias with penoscrotal transposition.

PMID- 27041474
TI  - Small molecule detection by lateral flow strips via aptamer-gated silica
      nanoprobes.
AB  - A fast, sensitive and ratiometric biosensor strategy for small molecule detection
      was developed through nanopore actuation. The new platform engineers together, a
      highly selective molecular recognition element, aptamers, and a novel signal
      amplification mechanism, gated nanopores. As a proof of concept, aptamer gated
      silica nanoparticles have been successfully used as a sensing platform for the
      detection of ATP concentrations at a wide linear range from 100 MUM up to 2 mM. 

PMID- 27041475
TI  - Severe or life-threatening asthma exacerbation: patient heterogeneity identified
      by cluster analysis.
AB  - BACKGROUND: Severe or life-threatening asthma exacerbation is one of the worst
      outcomes of asthma because of the risk of death. To date, few studies have
      explored the potential heterogeneity of this condition. OBJECTIVES: To examine
      the clinical characteristics and heterogeneity of patients with severe or life
      threatening asthma exacerbation. METHODS: This was a multicentre, prospective
      study of patients with severe or life-threatening asthma exacerbation and pulse
      oxygen saturation < 90% who were admitted to 17 institutions across Japan.
      Cluster analysis was performed using variables from patient- and physician
      orientated structured questionnaires. RESULTS: Analysis of data from 175 patients
      with severe or life-threatening asthma exacerbation revealed five distinct
      clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at
      baseline, including limitation of activities, a higher frequency of treatment
      with oral corticosteroids and short-acting beta-agonists, and a higher frequency
      of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly
      composed of elderly females, with the highest frequency of comorbid, chronic
      hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster
      3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline.
      Patients in this cluster had a higher frequency of atopy, including allergic
      rhinitis and furred pet hypersensitivity, and a better prognosis during
      hospitalization compared with the other clusters. Cluster 4 (n = 34) was
      characterized by elderly males with concomitant chronic obstructive pulmonary
      disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline
      according to the patient questionnaires, 41% had previously been hospitalized for
      asthma. CONCLUSIONS & CLINICAL RELEVANCE: This study demonstrated that
      significant heterogeneity exists among patients with severe or life-threatening
      asthma exacerbation. Differences were observed in the severity of asthma symptoms
      and use of inhaled corticosteroids at baseline, and the presence of comorbid
      COPD. These findings may contribute to a deeper understanding and better
      management of this patient population.

PMID- 27041476
TI  - Proximal Esophageal Varices: A Rare Yet Treatable Cause of Hemorrhage.

PMID- 27041477
TI  - Reply.

PMID- 27041478
TI  - Reply.

PMID- 27041479
TI  - Reply.

PMID- 27041481
TI  - Identification of Spongionella compounds as cyclosporine A mimics.
AB  - Marine sponges are found to be a wide source of bioactive compounds with
      different effects such as anti-inflammatory or anticancer actions among others.
      Cyclophilin A (Cyp A) is a target protein implicated in the mechanism of action
      of immunosuppressive compounds such as Cyclosporine A (CsA). In the present paper
      we studied the binding between 4 Spongionella compounds (Gracilins H, A, L and
      Tetrahydroaplysulphurin-1) and Cyp A immobilized over a CM5 sensor chip. Thus, we
      found that Spongionella compounds showed to have similar binding affinities than
      CsA with dissociation equilibrium constant in the range. Next, the effect of
      these Spongionella isolated compounds was tested over calcineurin phosphatase
      activity. The same than CsA, Gracilin H, A and Tetrahydroaplysulphurin-1 were
      able to inhibit phosphatase activity once the complex between Cyp A
      CsA/Spongionella compounds was formed. The ability to avoid the dephosphorylation
      of NFATc1 was also checked in human T cells isolated from peripheral blood.
      First, cells were pre-treated with Spongionella compounds or CsA following by
      Concanavalin A (Con A) stimulation. In these conditions nuclear NFATc1 levels
      were diminished either by CsA or Gracilin A, L, and Tetrahydroaplysulphurin-1
      treatment. Moreover, as happens with CsA due to the inhibition of NFATc1,
      Interleukine-2 (IL-2) released to the culture medium was significantly decreased
      with all Spongionella compounds. Results conclude that, Spongionella derivatives
      preserve T lymphocytes from activation modulating the same pathway than CsA.
      Thus, this mechanism of action suggests that these compounds could be interesting
      candidates in drug development as immunosuppressive or anti-inflammatory drugs.

PMID- 27041482
TI  - Sodium intake, RAAS-blockade and progressive renal disease.
AB  - Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by
      angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the
      current standard treatment to prevent progressive renal function loss in patients
      with chronic kidney disease. Yet in many patients the renal protective effect of
      RAAS-blockade is incomplete. Short-term clinical studies have demonstrated that
      dietary sodium restriction potentiates the antiproteinuric effect of RAAS
      blockade. More recently, it was shown that this effect is accompanied by a lower
      risk of end-stage renal disease and adverse cardiovascular outcomes. The
      modulation of RAAS-blockade efficacy by sodium intake is likely multifactorial,
      and is mediated by effects of sodium on local tissue RAAS in kidney, vasculature
      and brain, and by effects on the immune system. Despite the evidence showing the
      beneficial effects of even a moderate sodium restriction (~2.5g/d), it remains
      difficult to realize in clinical practice. In an analysis based on 24-h urinary
      sodium excretion data from more than 10,000 CKD patients and renal transplant
      recipients, we found that sodium intake in these patients is on average 3.8g/d,
      closely resembling the global general population (3.95g/d). Behavioral approaches
      including the use of online dietary coaching (ehealth) and feedback using data
      from 24-h urine collections may be useful to successfully lower dietary sodium
      intake, aiming to improve cardio-renal outcomes in patients with CKD.

PMID- 27041483
TI  - Apicomplexans pulling the strings: manipulation of the host cell cytoskeleton
      dynamics.
AB  - Invasive stages of apicomplexan parasites require a host cell to survive,
      proliferate and advance to the next life cycle stage. Once invasion is achieved,
      apicomplexans interact closely with the host cell cytoskeleton, but in many cases
      the different species have evolved distinct mechanisms and pathways to modulate
      the structural organization of cytoskeletal filaments. The host cell cytoskeleton
      is a complex network, largely, but not exclusively, composed of microtubules,
      actin microfilaments and intermediate filaments, all of which are modulated by
      associated proteins, and it is involved in diverse functions including
      maintenance of cell morphology and mechanical support, migration, signal
      transduction, nutrient uptake, membrane and organelle trafficking and cell
      division. The ability of apicomplexans to modulate the cytoskeleton to their own
      advantage is clearly beneficial. We here review different aspects of the
      interactions of apicomplexans with the three main cytoskeletal filament types,
      provide information on the currently known parasite effector proteins and
      respective host cell targets involved, and how these interactions modulate the
      host cell physiology. Some of these findings could provide novel targets that
      could be exploited for the development of preventive and/or therapeutic
      strategies.

PMID- 27041484
TI  - Methods for external disinfection of blow fly (Diptera: Calliphoridae) eggs prior
      to use in wound debridement therapy.
AB  - Maggot debridement therapy (MDT) is the use of the larval stage of flies (i.e.,
      Calliphoridae) to remove necrotic tissue and disinfect wounds. Effective MDT
      requires aseptic technique to prevent the unintentional introduction of
      pathogenic bacteria into a wound to be debrided; yet the external surface of
      Calliphoridae eggs is often heavily contaminated with bacteria. Studies of
      external disinfection of dipteran eggs have been reported, but neither their
      efficacy nor effect on egg viability has been adequately assessed. The present
      study evaluated the efficacy of ten disinfection techniques involving immersion,
      rinse, or a combination of both in formalin, Lysol, formaldehyde, bleach,
      ethanol, Sporgon, or benzalkonium chloride. All techniques resulted in
      significant decreases in culturable, aerobic bacterial load on Lucilia cuprina
      eggs. For L. cuprina, a 10 minute 3% Lysol immersion was the most efficacious,
      disinfecting 96.67% of egg samples, while resulting in 31.84% egg mortality. The
      5% formalin immersion was least efficacious, disinfecting only 3.33% of L.
      cuprina egg samples, while resulting in 33.51% egg mortality. A formaldehyde
      immersion, one of the most commonly used disinfection techniques, was moderately
      effective, disinfecting 66.7% of egg samples, while resulting in 40.16% egg
      mortality. For Chrysomya rufifacies and Cochliomyia macellaria egg samples, the
      10 minute 3% Lysol immersion disinfected 100% of the samples, and for Lucilia
      sericata, 80% of egg samples, while resulting in 33.97%, 7.34%, and 36.96% egg
      mortality, respectively. H2 CO disinfected 16.67% of Ch. rufifacies, 26.67% of C.
      macellaria, and 56.67% of L. sericata egg samples, while resulting in 21.98%,
      10.18%, and 32.19% egg mortality, respectively. Due to its high disinfection
      efficacy and relatively low egg mortality, a 10 minutes 3% Lysol immersion is
      recommended for sterilizing Calliphoridae eggs prior to rearing of larvae for use
      in MDT.

PMID- 27041485
TI  - Quantized conductance coincides with state instability and excess noise in
      tantalum oxide memristors.
AB  - Tantalum oxide memristors can switch continuously from a low-conductance
      semiconducting to a high-conductance metallic state. At the boundary between
      these two regimes are quantized conductance states, which indicate the formation
      of a point contact within the oxide characterized by multistable conductance
      fluctuations and enlarged electronic noise. Here, we observe diverse conductance
      dependent noise spectra, including a transition from 1/f(2) (activated transport)
      to 1/f (flicker noise) as a function of the frequency f, and a large peak in the
      noise amplitude at the conductance quantum GQ=2e(2)/h, in contrast to suppressed
      noise at the conductance quantum observed in other systems. We model the
      stochastic behaviour near the point contact regime using Molecular Dynamics
      Langevin simulations and understand the observed frequency-dependent noise
      behaviour in terms of thermally activated atomic-scale fluctuations that make and
      break a quantum conductance channel. These results provide insights into
      switching mechanisms and guidance to device operating ranges for different
      applications. 

PMID- 27041486
TI  - Modelling the nanomechanical response of a micro particle-matrix system for
      nanoindentation tests.
AB  - A lot of experimental, numerical simulation and analytical modelling work has
      been done on how the substrate affects the measured hardness and elastic modulus
      of the coating/substrate system for nanoindentation tests. Little work has been
      done on the elastic-plastic behaviour of micro particle-matrix systems. Clifford
      et al have proposed an empirical model to describe the spatially dependent
      composite modulus during nanoindentation tests for linear elastic particles
      embedded in a linear elastic matrix. However, no such models have been developed
      for elastic-plastic composites. In this study, finite element simulations were
      used to determine the elastic modulus and hardness of hard particles embedded in
      a soft matrix and vice versa. An extended Clifford model has been developed to
      determine the elastic modulus and hardness for elastic-plastic composites with
      various particle shapes and volume fractions. 

PMID- 27041487
TI  - Mentor-mentee relationship in medicine.
AB  - This study will review various aspects of the mentoring process, mainly in the
      medical field (both educational and research), in order to describe the mentor's
      role, the characteristics of the ideal mentor and mentee, how to find a good
      mentor, mentoring types, the benefits of a mentor-mentee relationship, and
      potential obstacles and possible solutions. Our ultimate goal is to encourage
      potential mentors to become actual mentors, and potential mentees to actively
      seek a mentor and not lose the opportunity to receive this precious gift that
      many of us have been fortunate to enjoy.

PMID- 27041480
TI  - Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular
      Disease.
AB  - BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events
      among high-risk persons and among those with a systolic blood pressure of 160 mm
      Hg or higher, but its role in persons at intermediate risk and with lower blood
      pressure is unclear. METHODS: In one comparison from a 2-by-2 factorial trial, we
      randomly assigned 12,705 participants at intermediate risk who did not have
      cardiovascular disease to receive either candesartan at a dose of 16 mg per day
      plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first
      coprimary outcome was the composite of death from cardiovascular causes, nonfatal
      myocardial infarction, or nonfatal stroke; the second coprimary outcome
      additionally included resuscitated cardiac arrest, heart failure, and
      revascularization. The median follow-up was 5.6 years. RESULTS: The mean blood
      pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in
      blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in
      the placebo group. The first coprimary outcome occurred in 260 participants
      (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group
      (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the
      second coprimary outcome occurred in 312 participants (4.9%) and 328 participants
      (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one
      of the three prespecified hypothesis-based subgroups, participants in the
      subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were
      in the active-treatment group had significantly lower rates of the first and
      second coprimary outcomes than those in the placebo group; effects were neutral
      in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in
      the two outcomes). CONCLUSIONS: Therapy with candesartan at a dose of 16 mg per
      day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with
      a lower rate of major cardiovascular events than placebo among persons at
      intermediate risk who did not have cardiovascular disease. (Funded by the
      Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov
      number, NCT00468923.).

PMID- 27041488
TI  - Immunolocalization of 5BrdU long retaining labeled cells and macrophage
      infiltration in the scarring limb of lizard after limb amputation.
AB  - After limb amputation in lizards no regeneration occurs following massive
      inflammatory reaction. Light immunocytochemistry for CD68 and ultrastructural
      observations show that numerous macrophages persist for over 18days post
      amputation in the limb and fibroblasts producing high levels of collagen are
      present underneath a differentiating wound epidermis. Injections of 5BrdU for 1
      week in normal lizards followed by a 4 weeks chase period indicate that most Long
      Retention Cells are present in the dense connectives of the dermis and inter
      muscle septa, sparse cells in bone marrow and epidermis and scattered cells in
      muscle satellite cells. Most of the fibrocytes forming the scarring outgrowth of
      the amputated limb likely derive from the proliferation of dermal and inter
      muscle fibrocytes after amputation. Differently from the tail where autotomous
      planes limit the extension of the damage, in the limb the injury produces massive
      tissue damage that favors intense and lasting inflammation. Numerous CD68 labeled
      macrophages likely stimulate fibroblast activation and rapid production of
      collagen fibrils underneath the wound epidermis. The latter does not form a
      growing apical region but rapidly differentiates into a mature epidermis so that
      no distal elongation of the limb occurs and a scar is instead formed. 

PMID- 27041489
TI  - Ancient human sialic acid variant restricts an emerging zoonotic malaria
      parasite.
AB  - Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing
      malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell
      (RBC) surface receptors, many of which are sialylated. While macaques synthesize
      the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because
      of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac)
      to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of
      Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P.
      knowlesi invasion ligands, PkDBPbeta and PkDBPgamma, bind specifically to Neu5Gc
      containing receptors. A human-adapted P. knowlesi line invades human RBCs
      independently of Neu5Gc, with duplication of the sialic acid-independent invasion
      ligand, PkDBPalpha and loss of PkDBPgamma. Our results suggest that absence of
      Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve
      to invade human RBCs through the use of sialic acid-independent pathways. 

PMID- 27041490
TI  - Is It Exertional Heatstroke or Something More? A Case Report.
AB  - BACKGROUND: Heat stroke, heat-related illness, and malignant hyperthermia all
      present with hyperthermia. The former two are common presentations in the
      emergency department (ED). On the other hand, malignant hyperthermia (MH) is an
      uncommon but equally dangerous condition that requires prompt recognition and
      specific treatment with dantrolene sodium and avoidance of certain medications to
      reduce morbidity and mortality. Recent research focusing on nonanesthetic or
      exercise-induced MH has demonstrated a relationship between certain gene
      mutations and malignant hyperthermia susceptibility. CASE REPORT: We report the
      case of a 19 year-old man with a family history of MH who was treated for
      exertional heat stroke, but despite cooling and adequate fluid resuscitation,
      demonstrated worsening rhabdomyolysis that subsequently responded to the
      administration of dantrolene sodium. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE
      OF THIS?: This case illustrates the importance of recognizing the potential
      relationship between exertional heat stroke and malignant hyperthermia. The
      overlap between heat stroke and malignant hyperthermia susceptibility has
      important implications in the treatment and evaluation of patients presenting
      with signs and symptoms of heat stroke or heat-related illness in the ED.

PMID- 27041491
TI  - Proposal of a New Approach to Study and Categorize Stress Hyperglycemia in Acute
      Myocardial Infarction.
AB  - BACKGROUND: Stress hyperglycemia (SH) is a valid prognosticator of in-hospital
      complications and mortality in the intensive care unit, and is universally
      available, simple, and cost-effective. Even small refinements of SH can improve
      the risk stratification of patients with one of the most important diseases today
      acute myocardial infarction (AMI). OBJECTIVE: The aim of the review was to
      analyze whether SH nomenclature and methodology have been consistent in the
      medical literature in order to identify possible methodological faults and to
      suggest possible solutions. DISCUSSION: SH nomenclature and glycemic targets have
      been relatively uniform in recent years, but there has been a pronounced
      variability in the methodology. Recent meta-analysis showed that AMI patients
      with new hyperglycemia had a 3.6-fold increased risk of mortality during
      hospitalization in comparison to those who were normoglycemic. Four SH
      methodological mistakes were identified. First, using one cutoff value for SH
      instead of two different values (one for patients with diabetes mellitus [DM] and
      one for patients without DM). Second, analyzing, for example, either tertiles or
      quintiles without dividing AMI patients into subgroups according to their DM
      status. Third, studying only two subgroups (with SH and without SH), without
      determining the presence of DM, when DM is not analyzed. Fourth, failure to
      measure glycated hemoglobin. CONCLUSIONS: The same admission blood glucose (BG)
      is a marker of different mortality risks in diabetic compared to nondiabetic AMI
      patients. For example, when admission BG is 108-126 mg/dL (6-7 mmol/L), then the
      risk of in-hospital mortality is higher in DM patients; however, with an
      admission BG of 162-180 mg/dL (9-10 mmol/L), the risk is lower in diabetic
      patients. We can improve the clinical utility of the admission BG in AMI if we
      analyze four groups of patients (those with and without previously diagnosed DM,
      and above and below the admission glycemia cutoff values for in-hospital
      mortality). Those cutoffs should be calculated separately for diabetic and
      nondiabetic AMI patients.

PMID- 27041492
TI  - Comparison of the QRS Complex, ST-Segment, and T-Wave Among Patients with Left
      Bundle Branch Block with and without Acute Myocardial Infarction.
AB  - BACKGROUND: The modified Sgarbossa criteria have been validated as a rule for
      diagnosis of acute coronary occlusion (ACO) in left bundle branch block (LBBB).
      However, no analysis has been done on differences in the QRS complex, T-wave, or
      ST-segment concordance of < 1 mm in the derivation or validation studies.
      Furthermore, there was no comparison of patients with acute myocardial infarction
      (AMI) but without ACO (i.e., non-ST-elevation myocardial infarction [non-STEMI])
      to patients with ACO or without AMI (no MI). OBJECTIVE: We compare findings
      involving the QRS amplitude, ST-segment morphology, ST-concordance < 1 mm, and T
      waves in patients with LBBB with ACO, non-STEMI, and no MI. METHODS:
      Retrospectively, emergency department patients were identified with LBBB and
      ischemic symptoms but no MI, with angiographically proven ACO, and with non
      STEMI. RESULTS: ACO, non-STEMI, and no MI groups consisted of 33, 24, and 105
      patients. The sum of the maximum deflection of the QRS amplitude across all leads
      (SigmaQRS) was smaller in patients with ACO than those without ACO (101.5 mm vs.
      132.5 mm; p < 0.0001) and a cutoff of SigmaQRS < 90 mm was 92% specific. For ACO,
      non-concave ST-segment morphology was 91% specific, any ST concordance >= 1 mm
      was 95% specific, and any ST concordance >= 0.5 mm was 94% sensitive. For non
      STEMI, terminal T-wave concordance, analogous to biphasic T-waves, was moderately
      sensitive at 79%. CONCLUSIONS: We found differences in QRS amplitude, ST-segment
      morphology, and T-waves between patients with LBBB and ACO, non-STEMI, and no MI.
      However, none of these criteria outperformed the modified Sgarbossa criteria for
      diagnosis of ACO in LBBB.

PMID- 27041493
TI  - 5-Demethylnobiletin and 5-Acetoxy-6,7,8,3',4'-pentamethoxyflavone Suppress Lipid
      Accumulation by Activating the LKB1-AMPK Pathway in 3T3-L1 Preadipocytes and High
      Fat Diet-Fed C57BL/6 Mice.
AB  - Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones (HPMFs), such as
      nobiletin (Nob) and 5-demethylnobiletin (5-OH-Nob), are unique flavonoids that
      are found exclusively in citrus peels. Nobiletin has been shown to suppress
      adipogenesis in vitro, but the antiadipogenic activity of 5-OH-Nob has not been
      investigated. Both nobiletin and 5-OH-Nob have poor aqueous solubility and low
      oral bioavailability. We employed chemical modification to produce the acetyl
      derivative of 5-OH-Nob, that is, 5-acetyloxy-6,7,8,3',4'-pentamethoxyflavone (5
      Ac-Nob), to improve its bioavailability and bioactive efficiency. We found that 5
      Ac-Nob reduced triacylglycerol (TG) content to a greater extent than 5-OH-Nob in
      3T3-L1 preadipocytes. Orally administered 5-Ac-Nob resulted in a significant
      reduction in body weight, intra-abdominal fat, plasma and liver TG levels, and
      plasma cholesterol level in high fat diet-induced obese male C57BL/6J mice. The 5
      Ac-Nob treatment decreased lipid accumulation by triggering the adenosine 5'
      monophosphate-activated protein kinase (AMPK) pathway to alter transcriptional
      factors or lipogenesis-related enzymes in vivo and in vitro. 

PMID- 27041494
TI  - Speech discrimination in 11-month-old bilingual and monolingual infants: a
      magnetoencephalography study.
AB  - Language experience shapes infants' abilities to process speech sounds, with
      universal phonetic discrimination abilities narrowing in the second half of the
      first year. Brain measures reveal a corresponding change in neural discrimination
      as the infant brain becomes selectively sensitive to its native language(s).
      Whether and how bilingual experience alters the transition to native language
      specific phonetic discrimination is important both theoretically and from a
      practical standpoint. Using whole head magnetoencephalography (MEG), we examined
      brain responses to Spanish and English syllables in Spanish-English bilingual and
      English monolingual 11-month-old infants. Monolingual infants showed sensitivity
      to English, while bilingual infants were sensitive to both languages. Neural
      responses indicate that the dual sensitivity of the bilingual brain is achieved
      by a slower transition from acoustic to phonetic sound analysis, an adaptive and
      advantageous response to increased variability in language input. Bilingual
      neural responses extend into the prefrontal and orbitofrontal cortex, which may
      be related to their previously described bilingual advantage in executive
      function skills. A video abstract of this article can be viewed at:
      https://youtu.be/TAYhj-gekqw.

PMID- 27041495
TI  - Cardiovascular progenitor-derived extracellular vesicles recapitulate the
      beneficial effects of their parent cells in the treatment of chronic heart
      failure.
AB  - BACKGROUND: Cell-based therapies are being explored as a therapeutic option for
      patients with chronic heart failure following myocardial infarction.
      Extracellular vesicles (EV), including exosomes and microparticles, secreted by
      transplanted cells may orchestrate their paracrine therapeutic effects. We
      assessed whether post-infarction administration of EV released by human embryonic
      stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent
      benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate
      similar endogenous pathways. METHODS: Mice underwent surgical occlusion of their
      left coronary arteries. After 2-3 weeks, 95 mice included in the study were
      treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM;
      vehicle control) delivered by percutaneous injections under echocardiographic
      guidance into the peri-infarct myocardium. functional and histologic end-points
      were blindly assessed 6 weeks later, and hearts were processed for gene
      profiling. Genes differentially expressed between control hearts and hESC-Pg
      treated and EV-treated hearts were clustered into functionally relevant pathways.
      RESULTS: At 6 weeks after hESC-Pg administration, treated mice had significantly
      reduced left ventricular end-systolic (-4.20 +/- 0.96 ul or -7.5%, p = 0.0007)
      and end-diastolic (-4.48 +/- 1.47 ul or -4.4%, p = 0.009) volumes compared with
      baseline values despite the absence of any transplanted hESC-Pg or human
      embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal
      benefits were seen with the injection of hESC-Pg-derived EV, whereas animals
      injected with alpha-MEM (vehicle control) did not improve significantly.
      Histologic examination suggested a slight reduction in infarct size in hESC-Pg
      treated animals and EV-treated animals compared with alpha-MEM-treated control
      animals. In the hESC-Pg-treated and EV-treated groups, heart gene profiling
      identified 927 genes that were similarly upregulated compared with the control
      group. Among the 49 enriched pathways associated with these up-regulated genes
      that could be related to cardiac function or regeneration, 78% were predicted to
      improve cardiac function through increased cell survival and/or proliferation or
      DNA repair as well as pathways related to decreased fibrosis and heart failure.
      CONCLUSIONS: In this post-infarct heart failure model, either hESC-Pg or their
      secreted EV enhance recovery of cardiac function and similarly affect cardiac
      gene expression patterns that could be related to this recovery. Although the
      mechanisms by which EV improve cardiac function remain to be determined, these
      results support the idea that a paracrine mechanism is sufficient to effect
      functional recovery in cell-based therapies for post-infarction-related chronic
      heart failure.

PMID- 27041496
TI  - Right ventricular afterload sensitivity dramatically increases after left
      ventricular assist device implantation: A multi-center hemodynamic analysis.
AB  - BACKGROUND: Right ventricular (RV) failure is a source of morbidity and mortality
      after left ventricular assist device (LVAD) implantation. In this study we sought
      to define hemodynamic changes in afterload and RV adaptation to afterload both
      early after implantation and with prolonged LVAD support. METHODS: We reviewed
      right heart catheterization (RHC) data from participants who underwent continuous
      flow LVAD implantation at our institutions (n = 244), excluding those on
      inotropic or vasopressor agents, pulmonary vasodilators or additional mechanical
      support at any RHC assessment. Hemodynamic data were assessed at 5 time
      intervals: (1) pre-LVAD (within 6 months); (2) early post-LVAD (0 to 6 months);
      (3) 7 to 12 months; (4) 13 to 18 months; and (5) very late post-LVAD (18 to 36
      months). RESULTS: Sixty participants met the inclusion criteria. All measures of
      right ventricular load (effective arterial elastance, pulmonary vascular
      compliance and pulmonary vascular resistance) improved between the pre- and early
      post-LVAD time periods. Despite decreasing load and pulmonary artery wedge
      pressure (PAWP), RAP remained unchanged and the RAP:PAWP ratio worsened early
      post-LVAD (0.44 [0.38, 0.63] vs 0.77 [0.59, 1.0], p < 0.001), suggesting a
      worsening of RV adaptation to load. With continued LVAD support, both RV load and
      RAP:PAWP decreased in a steep, linear and dependent manner. CONCLUSIONS: Despite
      reducing RV load, LVAD implantation leads to worsened RV adaptation. With
      continued LVAD support, both RV afterload and RV adaptation improve, and their
      relationship remains constant over time post-LVAD. These findings suggest the RV
      afterload sensitivity increases after LVAD implantation, which has major clinical
      implications for patients struggling with RV failure.

PMID- 27041497
TI  - Morphological Substrates for Parallel Streams of Corticogeniculate Feedback
      Originating in Both V1 and V2 of the Macaque Monkey.
AB  - Corticothalamic circuits are essential for reciprocal information exchange
      between the thalamus and cerebral cortex. Nevertheless, the role of
      corticothalamic circuits in sensory processing remains a mystery. In the visual
      system, afferents from retina to the lateral geniculate nucleus (LGN) and from
      LGN to primary visual cortex (V1) are organized into functionally distinct
      parallel processing streams. Physiological evidence suggests corticogeniculate
      feedback may be organized into parallel streams; however, little is known about
      the diversity of corticogeniculate neurons, their local computations, or the
      structure-function relationship among corticogeniculate neurons. We used a virus
      mediated approach to label and reconstruct the complete dendritic and local
      axonal arbors of identified corticogeniculate neurons in the macaque monkey. Our
      results reveal morphological substrates for parallel streams of corticogeniculate
      feedback based on distinct classes of neurons in V1 and V2. These results support
      the hypothesis that distinct populations of feedback neurons provide independent
      and unique information to the LGN.

PMID- 27041498
TI  - Inhibition, Not Excitation, Drives Rhythmic Whisking.
AB  - Sniffing and whisking typify the exploratory behavior of rodents. These actions
      involve separate oscillators in the medulla, located respectively in the pre
      Botzinger complex (preBotC) and the vibrissa-related region of the intermediate
      reticular formation (vIRt). We examine how these oscillators synergize to control
      sniffing and whisking. We find that the vIRt contains glycinergic/GABAergic cells
      that rhythmically inhibit vibrissa facial motoneurons. As a basis for the
      entrainment of whisking by breathing, but not vice versa, we provide evidence for
      unidirectional connections from the preBotC to the vIRt. The preBotC further
      contributes to the control of the mystacial pad. Lastly, we show that bilateral
      synchrony of whisking relies on the respiratory rhythm, consistent with
      commissural connections between preBotC cells. These data yield a putative
      circuit in which the preBotC acts as a master clock for the synchronization of
      vibrissa, pad, and snout movements, as well as for the bilateral synchronization
      of whisking.

PMID- 27041499
TI  - Divergent Routing of Positive and Negative Information from the Amygdala during
      Memory Retrieval.
AB  - Although the basolateral amygdala (BLA) is known to play a critical role in the
      formation of memories of both positive and negative valence, the coding and
      routing of valence-related information is poorly understood. Here, we recorded
      BLA neurons during the retrieval of associative memories and used optogenetic
      mediated phototagging to identify populations of neurons that synapse in the
      nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus
      (vHPC). We found that despite heterogeneous neural responses within each
      population, the proportions of BLA-NAc neurons excited by reward predictive cues
      and of BLA-CeA neurons excited by aversion predictive cues were higher than
      within the entire BLA. Although the BLA-vHPC projection is known to drive
      behaviors of innate negative valence, these neurons did not preferentially code
      for learned negative valence. Together, these findings suggest that valence
      encoding in the BLA is at least partially mediated via divergent activity of
      anatomically defined neural populations.

PMID- 27041500
TI  - Excitation-Transcription Coupling in Parvalbumin-Positive Interneurons Employs a
      Novel CaM Kinase-Dependent Pathway Distinct from Excitatory Neurons.
AB  - Properly functional CNS circuits depend on inhibitory interneurons that in turn
      rely upon activity-dependent gene expression for morphological development,
      connectivity, and excitatory-inhibitory coordination. Despite its importance,
      excitation-transcription coupling in inhibitory interneurons is poorly
      understood. We report that PV+ interneurons employ a novel CaMK-dependent pathway
      to trigger CREB phosphorylation and gene expression. As in excitatory neurons,
      voltage-gated Ca(2+) influx through CaV1 channels triggers CaM nuclear
      translocation via local Ca(2+) signaling. However, PV+ interneurons are distinct
      in that nuclear signaling is mediated by gammaCaMKI, not gammaCaMKII. CREB
      phosphorylation also proceeds with slow, sigmoid kinetics, rate-limited by
      paucity of CaMKIV, protecting against saturation of phospho-CREB in the face of
      higher firing rates and bigger Ca(2+) transients. Our findings support the
      generality of CaM shuttling to drive nuclear CaMK activity, and they are relevant
      to disease pathophysiology, insofar as dysfunction of PV+ interneurons and
      molecules underpinning their excitation-transcription coupling both relate to
      neuropsychiatric disease.

PMID- 27041501
TI  - Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C. elegans.
AB  - Thermosensation is critical for optimal regulation of physiology and behavior. C.
      elegans acclimates to its cultivation temperature (Tc) and exhibits
      thermosensitive behaviors at temperatures relative to Tc. These behaviors are
      mediated primarily by the AFD sensory neurons, which are extraordinarily
      thermosensitive and respond to thermal fluctuations at temperatures above a Tc
      determined threshold. Although cGMP signaling is necessary for
      thermotransduction, the thermosensors in AFD are unknown. We show that AFD
      specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation.
      In addition to being necessary for thermotransduction, ectopic expression of
      these rGCs confers highly temperature-dependent responses onto diverse cell
      types. We find that the temperature response threshold is determined by the rGC
      and cellular context, and that multiple domains contribute to their thermosensory
      properties. Identification of thermosensory rGCs in C. elegans provides insight
      into mechanisms of thermosensation and thermal acclimation and suggests that rGCs
      may represent a new family of molecular thermosensors.

PMID- 27041502
TI  - Perisaccadic Receptive Field Expansion in the Lateral Intraparietal Area.
AB  - Humans and monkeys have access to an accurate representation of visual space
      despite a constantly moving eye. One mechanism by which the brain accomplishes
      this is by remapping visual receptive fields around the time of a saccade. In
      this process a neuron can be excited by a probe stimulus in the current receptive
      field, and also simultaneously by a probe stimulus in the location that will be
      brought into the neuron's receptive field by the saccade (the future receptive
      field), even before saccade begins. Here we show that perisaccadic neuronal
      excitability is not limited to the current and future receptive fields but
      encompasses the entire region of visual space across which the current receptive
      field will be swept by the saccade. A computational model shows that this
      receptive field expansion is consistent with the propagation of a wave of
      activity across the cerebral cortex as saccade planning and remapping proceed.

PMID- 27041504
TI  - Rapid improvement of olfaction after lumbar puncture in a patient with idiopathic
      intracranial hypertension.

PMID- 27041505
TI  - Improving the stability and inertness of Cu(ii) and Cu(i) complexes with
      methylthiazolyl ligands by tuning the macrocyclic structure.
AB  - A tacn based ligand bearing two methylthiazolyl arms (no2th) was synthesized with
      the aim to find ligands forming very stable and inert complexes with Cu(ii) and
      Cu(i) in aqueous medium for radiopharmaceutical applications. The no2th ligand
      was efficiently prepared following the orthoamide intermediate synthesis. The
      complexes with Cu(2+) and Zn(2+) were obtained and analyzed by X-ray diffraction.
      The [Cu(no2th)](2+) complex presents a pentacoordinated distorted square
      pyramidal coordination geometry, while the metal ion in [Zn(no2th)](2+) adopts a
      hexacoordinated distorted trigonal prismatic geometry involving the coordination
      of a perchlorate counter ion. The acid-base properties of no2th have been studied
      using potentiometric titrations, and the stability constants of Cu(2+) and Zn(2+)
      complexes were determined by potentiometric and UV-vis titrations using H4edta as
      a competitor ligand. The stability constant determined for the Cu(2+) complex is
      rather high (log KCuL = 20.77 and pCu = 17.15), and moreover no2th exhibits a
      high selectivity for copper(ii) in relation to zinc(ii). The kinetics of the
      copper(ii) complexation process is very fast even in acidic medium. In addition,
      the [Cu(no2th)](2+) complex was found to be inert under rather harsh conditions
      (up to 2 M HCl and 60  degrees C), displaying a very high half-life time of about
      15 days in 2 M HCl at 90  degrees C. The electrochemical reduction of the
      copper(ii) complex in water leads to the reversible formation of a stable
      copper(i) species. Spectroscopic studies performed by NMR, UV-vis and EPR,
      assisted by theoretical calculations, show that the [Cu(no2th)](2+) complex
      presents a structure in solution similar to that observed in the solid state.
      When compared to its cyclam di-N-methylthiazolyl counterpart, the results
      reported in this paper unambiguously show that replacing the cyclam unit by a
      tacn moiety improves the stability and inertness of its Cu(ii) and Cu(i)
      complexes.

PMID- 27041506
TI  - Categorical representation of North American precipitation projections.
AB  - We explore use of the familiar tercile framework of seasonal forecasting for the
      characterization of 21st-century precipitation projections over North America.
      Consistent with direct analyses of modeled precipitation change, in a
      superensemble of CMIP5 simulations an unambiguous pattern of shifted tercile
      population statistics develops as the globe warms. Expressed categorically,
      frequencies for the low (i.e., dry) tercile increase in the southwestern United
      States and southward into Mexico and decrease across the northern tier of North
      America, while counts for the high tercile shift in the opposite sense. We show
      that as the 21st-century proceeds, changes become statistically significant over
      wide regions in the pointwise sense, and also when considered as projections on
      model-specific climate change "fingerprints". Background noise in the
      superensemble, against which significance is established, comprises both
      structural model uncertainty and natural climate variability. The robustness of
      these findings makes a compelling case for long-range planning for a dryer future
      in the American Southwest and southward, and wetter one to the north and
      especially northeast, while communication is facilitated by widespread user
      familiarity with the tercile format. 

PMID- 27041503
TI  - Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and
      Promotes Tauopathy-Related Memory Loss.
AB  - Tau toxicity has been implicated in the emergence of synaptic dysfunction in
      Alzheimer's disease (AD), but the mechanism by which tau alters synapse
      physiology and leads to cognitive decline is unclear. Here we report abnormal
      acetylation of K274 and K281 on tau, identified in AD brains, promotes memory
      loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin
      (KIBRA) protein, a memory-associated protein. Transgenic mice expressing human
      tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ)
      exhibit AD-related memory deficits and impaired hippocampal long-term
      potentiation (LTP). TauKQ reduces synaptic KIBRA levels and disrupts activity
      induced postsynaptic actin remodeling and AMPA receptor insertion. The LTP
      deficit was rescued by promoting actin polymerization or by KIBRA expression. In
      AD patients with dementia, we found enhanced tau acetylation is linked to loss of
      KIBRA. These findings suggest a novel mechanism by which pathogenic tau causes
      synaptic dysfunction and cognitive decline in AD pathogenesis.

PMID- 27041507
TI  - Consolidative treatment after salvage chemotherapy improves prognosis in patients
      with relapsed extranodal natural killer/T-cell lymphoma.
AB  - The optimal treatment strategy for relapsed natural killer/T-cell lymphoma
      (NKTCL) remains largely unknown. We retrospectively reviewed the treatment
      modalities and prognosis of 56 relapsed NKTCL patients. Chemotherapy was the
      initial salvage treatment, followed by radiotherapy (RT) or autologous
      hematopoietic stem cell transplantation (AHSCT) as consolidative therapy,
      depending on the status of remission and the pattern of relapse. For patients
      with locoregional relapse alone, consolidative RT after salvage chemotherapy
      significantly improved prognosis compared with follow-up (5-year OS: 83.3 vs.
      41.7%, P = 0.047). For patients with distant relapse, consolidative AHSCT after
      salvage chemotherapy significantly prolonged survival compared with follow-up (2
      year OS: 100.0 vs. 20.0%, P = 0.004). Patients without consolidative treatment
      after response to salvage chemotherapy exhibited a comparable survival to those
      who experienced stable or progressive disease after chemotherapy. Asparaginase
      (ASP)-containing salvage chemotherapy failed to confer a survival advantage over
      ASP-absent chemotherapy (5-year OS: 44.2 vs. 39.3%, P = 0.369). In conclusion,
      consolidative RT or AHSCT improved prognosis in patients with relapsed NKTCL who
      responded to initial salvage chemotherapy, and the role of ASP in salvage
      chemotherapy requires further exploration in prospective studies.

PMID- 27041508
TI  - The Swedish National Diabetes Register in clinical practice and evaluation in
      primary health care.
AB  - : Aim The purpose of this project is to describe the use of the Swedish National
      Diabetes Register (NDR) in clinical practice in a Swedish county and to
      specifically monitor the diabetes care routines at two separate primary health
      care centres (PHCC) with a special focus on older patients. BACKGROUND: According
      to Swedish law, all health-care units have to maintain a system for quality
      evaluation and improvement. As the NDR holds the most important quality
      indicators, implementation of the NDR in primary care was carried out by an
      implementation project in 2002-2005. METHODS: Initially, a digital questionnaire
      about NDR routines was sent to all PHCC. Statistics about hemoglobin adult 1c
      (HbA1c) and blood pressure (BP) was presented for the diabetes teams at two
      centres who were also interviewed. The responses became the basis for a focus
      group interview with both teams together, with data subject to content analysis.
      Findings The study showed that reporting to the NDR has become a compulsory
      routine in primary care. The diabetes nurse specialist was responsible for the
      practical management of the register and used the NDR for continuous monitoring
      of the patients. Most centres used the NDR's statistics for evaluation and
      analyses annually. The diabetes nurse adapted the visits to the patient's wishes
      and general condition. Only in terms of target values for HbA1c and BP did they
      accept slightly higher values for the older patients. Since the NDR was
      implemented, the registration rate has remained at 75% and has not increased. The
      reason given was that patients with diabetes living in nursing homes are checked
      up by the municipal nurse who does not use the NDR. However, the risk of omitting
      older patients in the NDR could be considerably decreased if data could be
      transferred from the electronic patient record.

PMID- 27041509
TI  - Tailoring Novel PTFE Surface Properties: Promoting Cell Adhesion and Antifouling
      Properties via a Wet Chemical Approach.
AB  - Many biomaterials used for tissue engineering applications lack cell-adhesiveness
      and, in addition, are prone to nonspecific adsorption of proteins. This is
      especially important for blood-contacting devices such as vascular grafts and
      valves where appropriate surface properties should inhibit the initial attachment
      of platelets and promote endothelial cell colonization. As a consequence, the
      long-term outcome of the implants would be improved and the need for
      anticoagulation therapy could be reduced or even abolished.
      Polytetrafluoroethylene (PTFE), a frequently used polymer for various medical
      applications, was wet-chemically activated and subsequently modified by grafting
      the endothelial cell (EC) specific peptide arginine-glutamic acid-aspartic acid
      valine (REDV) using a bifunctional polyethylene glycol (PEG)-spacer (known to
      reduce platelet and nonspecific protein adhesion). Modified and control surfaces
      were both evaluated in terms of EC adhesion, colonization, and the attachment of
      platelets. In addition, samples underwent bacterial challenges. The results
      strongly suggested that PEG-mediated peptide immobilization renders PTFE an
      excellent substrate for cellular growth while simultaneously endowing the
      material with antifouling properties.

PMID- 27041510
TI  - Infection of J774A.1 with different Mycobacterium species induces differential
      immune and miRNA-related responses.
AB  - Macrophages act as a reservoir for Mycobacterium tuberculosis, producing latent
      infection in approximately 90% of infected people. In this study, J774A.1 mouse
      macrophage cell line response and microRNA (miRNA) expression during infection
      with the most relevant mycobacterial strains for humans (M. tuberculosis, M.
      bovis and M. bovis BCG) was explored. No significant differences in bacillary
      loads were observed between activate and naive macrophages infected with M.
      tuberculosis and M. bovis. Nitrite production inhibition and infection control
      were in accordance with the virulence of the strain. Expression of let-7e, miR
      21, miR-155, miR-210 and miR-223 was opposite in the two species and miR-146b*
      and miR-1224 expression seemed to be part of the general response to infection. 

PMID- 27041511
TI  - Gel Permeation HPLC Analysis Validates a Classical Spherical Space-filling Model
      for Lipoprotein Structure Opening Future Potential of the Technology.

PMID- 27041512
TI  - Recent Advances in Analytical Methods on Lipoprotein Subclasses: Calculation of
      Particle Numbers from Lipid Levels by Gel Permeation HPLC Using "Spherical
      Particle Model".
AB  - Recently, we developed an analytical method for determining the lipid levels and
      particle numbers in lipoprotein subclasses covering a wide size range from
      chylomicrons to small high density lipoproteins, by using gel permeation high
      performance liquid chromatography (GP-HPLC). The challenges in analytical methods
      on lipoprotein subclasses have been addressed from 1980 by Hara and Okazaki using
      commercial TSK gel permeation columns. Later, the improvements in the hardware,
      separation and detection of lipoproteins, and the data processing software, using
      a Gaussian distribution approximation to calculate lipid levels of lipoprotein
      subclasses, have been extensively utilized in these analytical methods for over
      thirty years. In this review, we describe on the recent advances in analytical
      methods on lipoprotein subclasses based on various techniques, and the
      calculation of particle numbers from lipid levels by GPHPLC using the "spherical
      particle model". Free/ester ratio of cholesterol in particular lipoprotein
      subclass was accurately estimated from triglyceride, total cholesterol (free and
      esterified) and the size of the particle based on this model originally proposed
      by Shen and Kezdy. 

PMID- 27041513
TI  - Recovery of Palm Oil and Valuable Material from Oil Palm Empty Fruit Bunch by Sub
      critical Water.
AB  - Oil palm empty fruit bunch (EFB) is one of the solid wastes produced in huge
      volume by palm oil mill. Whilst it still contains valuable oil, approximately
      22.6 million tons is generated annually and treated as solid waste. In this work,
      sub-critical water (sub-cw) was used to extract oil, sugar and tar from spikelet
      of EFB. The spikelet was treated with sub-cw between 180-280 degrees C and a
      reaction time of 2 and 5 minutes. The highest yield of oil was 0.075 g-oil/g-dry
      EFB, obtained at 240 degrees C and reaction time of 5 minutes. Astonishingly, oil
      that was extracted through this method was 84.5% of that obtained through Soxhlet
      method using hexane. Yield of oil extracted was strongly affected by the reaction
      temperature and time. Higher reaction temperature induces the dielectric constant
      of water towards the non-polar properties of solvent; thus increases the oil
      extraction capability. Meanwhile, the highest yield of sugar was 0.20 g-sugar/g
      dry EFB obtained at 220 degrees C. At this temperature, the ion product of water
      is high enough to enable maximum sub-critical water hydrolysis reaction. This
      study showed that oil and other valuable material can be recovered using water at
      sub-critical condition, and most attractive without the use of harmful organic
      solvent. 

PMID- 27041514
TI  - Effects of Initial Pore Diameter on the Oil Absorption Behavior of Potato Chips
      during Frying Process.
AB  - How initial pore diameter in materials affects oil absorption has been rarely
      studied up to now. Herein, we provided direct data evidence suggesting that the
      pore diameter prior to frying closely related to the oil absorption behavior. The
      pore had no significant effect on oil absorption of potato chips (p>0.05) when
      its diameter was 0.1 and 0.2 mm compared with the control. However, the oil
      absorption increased with the increasing of pore diameter when it was 0.3-1.2 mm.
      The oil absorption tended to be saturated at 0.9 mm pore diameter. In addition,
      we analyzed the moisture content, total oil (TO), surface oil (SO), penetrated
      surface oil (PSO) and structural oil (STO) contents of potato chips. The results
      when using palm oil showed that there was no significant difference in moisture,
      TO and STO contents of samples with pore diameter of 0.1 and 0.2 mm during the
      whole frying processing respectively compared with the control (p>0.05). When
      pore diameter was 0.3-1.2 mm, STO and TO contents significantly increased with
      the rising of the diameter (p<0.05). The SO content and PSO content dropped as
      increasing in frying time for the samples with different pore diameters. The
      equilibrium TO content of samples with 0.3-0.9 mm pore significantly increased
      with the rising of pore diameter, which was about 6.2-22.5% higher than that of
      the control. And there was no significant difference in the equilibrium TO
      contents of both samples of 1.2 mm and 0.9 mm pore (p>0.05). STO fraction gave
      the greatest contribution to the increment of oil absorption. 

PMID- 27041515
TI  - Catalytic Ethanol Dehydration over Different Acid-activated Montmorillonite
      Clays.
AB  - In the present study, the catalytic dehydration of ethanol to obtain ethylene
      over montmorillonite clays (MMT) with mineral acid activation including H2SO4 (SA
      MMT), HCl (HA-MMT) and HNO3 (NA-MMT) was investigated at temperature range of 200
      to 400 degrees C. It revealed that HA-MMT exhibited the highest catalytic
      activity. Ethanol conversion and ethylene selectivity were found to increase with
      increased reaction temperature. At 400 degrees C, the HA-MMT yielded 82% of
      ethanol conversion having 78% of ethylene yield. At lower temperature (i.e. 200
      to 300 degrees C), diethyl ether (DEE) was a major product. The highest activity
      obtained from HA-MMT can be attributed to an increase of weak acid sites and acid
      density by the activation of MMT with HCl. It can be also proven by various
      characterization techniques that in most case, the main structure of MMT did not
      alter by acid activation (excepted for NA-MMT). Upon the stability test for 72 h
      during the reaction, the MMT and HA-MMT showed only slight deactivation due to
      carbon deposition. Hence, the acid activation of MMT by HCl is promising to
      enhance the catalytic dehydration of ethanol. 

PMID- 27041516
TI  - Errata for J. Oleo Science, Vol.65, No.1, pp.1 (2016).

PMID- 27041517
TI  - Profiling Fanconi Anemia Gene Mutations among Iranian Patients.
AB  - BACKGROUND: Fanconi anemia (FA) is a rare genetic syndrome characterized by
      developmental defects, bone marrow failure, and a high cancer risk. FA is usually
      inherited as an autosomal recessive condition. This disease is genetically
      heterogeneous and mutations in 16 different genes have been identified in FA
      patients to date. An accurate diagnosis needs detection of pathogenic variations
      in the FA genes along with positive results from chromosome breakage test.
      METHODS: In this study, 48 families with at least 2 affected FA patients and
      positive chromosome breakage test were enrolled from the Iranian population.
      Molecular analysis of FA genes was performed using Next Generation Sequencing
      (NGS) method and Multiple Ligation Dependent Probe Amplification (MLPA). RESULTS:
      Causal mutations for 30 (63%) patients were identified in homozygous or compound
      heterozygous forms. FANCA had the highest mutation frequency rate (83%) followed
      by FANCG (10%), FANCD2 (3%) and FANCL (3%). A significant proportion (44%) of
      FANCA mutations were large rearrangements. CONCLUSION: Genetic testing for FA
      patients improves the accuracy of diagnosis and also will be essential for
      genetic counselling and prenatal diagnosis for future pregnancies in the family.
      Availability of NGS technology has made the screening of all known FA genes at
      once more practical and affordable.

PMID- 27041518
TI  - Burden of Malaria in Iran, 1990-2010: Findings from the Global Burden of Disease
      Study 2010.
AB  - BACKGROUND: Malaria is a major public health challenge in tropical and semi
      tropical countries in terms of high morbidity and mortality. The present study
      aimed to report the burden of malaria in Iran, extracted from the global burden
      of disease 2010 study (GBD 2010) covering the period 1990 to 2010, to compare
      these findings with similar results, and to present some recommendations as
      potential solutions for gaining more accurate estimations regarding the burden of
      the disease in Iran. METHODS: Data covering the period from 1990 to 2010 were
      derived from the GBD 2010, which is published by the Institute for Health Metrics
      and Evaluation (IHME). The findings were used to estimate the years lived with
      disability (YLDs), the years of life lost (YLLs), the disability-adjusted life
      years (DALYs), and the death rate of malaria in Iran. RESULTS: The GBD 2010
      estimated that there was a sharp declining death trend with regard to DALYs and
      death rate, showing that 4,647.63 DALYs were due to malaria in Iranian people of
      all ages and both genders, and that DALYs per 100,000 individuals declined from
      37.15 in 1990 to 5.87 in 2010. The total number of malaria deaths over the 20
      years was 73.37. CONCLUSION: The findings revealed that the burden of malaria
      decreased remarkably between 1990 and 2010. The explanation for this decrease is
      the establishment of a malaria surveillance system in various parts of Iran, and
      utilization of proper intervention and the improvement of infrastructures, which
      play a role in disease transmission, especially in endemic areas.

PMID- 27041519
TI  - Major Dietary Protein Sources in Relation to Pancreatic Cancer: a Large
      Prospective Study.
AB  - INTRODUCTION: Current evidence is inconsistent about the association between
      dietary protein intake and risk of pancreatic cancer (PC). The aim of this study
      was to evaluate the association between total intake of major dietary protein
      sources and risk of PC in a large prospective study in Golestan Cohort Study
      (GCS). METHODS: We examined the association of total intake of major dietary
      protein sources with risk of PC in the 50,045 participants (20,855 men and 28,255
      women) of the GCS in northeastern Iran. Participants were aged 40 and older at
      baseline and actively followed from 2004 to the present time. Dietary data were
      collected using a validated semi-quantitative food-frequency questionnaire that
      was administered at baseline. Cox proportional hazards models were used to
      estimate Multivariable hazard ratios with 95% confidence intervals (CI). RESULTS:
      During 383,630 person-years of follow-up, 54 cases of pancreatic cancer were
      ascertained. There was only a statistically significant inverse association
      between risk of PC for the second versus lowest tertile of plant based protein
      intake in the first and multivariable models (HR = .27, 95% CI = .12-.64, HR =
      .28, 95% CI = .12 -.65 respectively); however, this association was not
      significant  anymore when comparing the highest tertile with the lowest one, in
      the first and multivariable models (HR = .49, 95% CI = .19-1.24, HR = .52, 95% CI
      = .20-1.34 respectively). CONCLUSION: In this large prospective cohort, we did
      not observe any clear and consistent evidence for an association between main
      dietary.

PMID- 27041520
TI  - Prevalence of Cognitive Disorders in Patients with Systemic Lupus Erythromatosus;
      a Cross-sectional Study in Rasoul-e-Akram Hospital, Tehran, Iran.
AB  - BACKGROUND: Neuropsychological manifestations are present in 60% of patients with
      Systemic Lupus Erythematosus (SLE) among which cognitive dysfunction is the most
      common. This study aims to determine the prevalence of cognitive disorders in SLE
      patients, and the relationship between cognitive disorder domains and depression
      and anxiety. METHODS: In this cross-sectional study, 54 patients with SLE and 48
      healthy subjects were included. Mini-Mental State Examination (MMSE), Clock
      Drawing Test (CDT) and Trail Making Test part A (TMT-A) were used to screen for
      cognitive impairments. All subjects were evaluated with the Beck Depression
      Inventory (BDI) and the Beck Anxiety Inventory (BAI) to determine depression and
      anxiety as probable confounding variables. RESULTS: The mean MMSE scores in SLE
      and control group patients (26.12 +/- 3.58 and 28.01 +/- 1.99, respectively) were
      significantly different (P = 0.001). The sub-scores in all areas assessed with
      MMSE were lower in SLE patients; however, it was only significant in the areas of
      orientation, recall and language (P < 0.05). SLE patients showed a significantly
      poorer performance in TMT compared to healthy controls (P = 0.01). The CDT
      according to the Watson scoring system showed significant difference between the
      two groups (P = 0.03). The Sunderland scoring system also indicated poorer
      performance in the SLE group, but the difference was not significant. CONCLUSION:
      Our study showed that cognitive disorders are more than 3-fold higher in SLE
      patients compared to normal subjects. The most impaired domains include
      orientation, Memory (recall), Language, Executive function, and psychomotor
      speed. Anxiety and depression are mostly correlated with domains included in the
      MMSE test.

PMID- 27041521
TI  - Management of Anesthesia during Lung Transplantations in a Single Turkish Center.
AB  - AIM: The aim of this study is to present our institutional experience during the
      management of anesthesia in lung transplantation (LT) surgeries as a definitive
      surgical treatment option in end-stage lung diseases. METHODS: From a total of 15
      patients, lung transplantation was performed as single LT (SLT) in 4 patients (n
      = 4) and as sequential bilateral LT (BLT) in 11 patients (n = 11). The anesthetic
      management included; for induction; intravenous ketamine, midazolam at doses of 2
      mg/kg, 0.05 mg/kg, respectively or propofol, fentanyl at doses of 1 mg/kg, 3
      mcg/kg, respectively. For maintenance, all patients received; 100% O2 and total
      intravenous infusion of propofol and remifentanil at doses of 0.02 mcg/kg/min and
      0.1-0.25 ug/kg/min, respectively. All patients received intravenous rocuronium
      bromide for induction and maintenance. Hemodynamic stability was maintained with
      appropriate and adequate administration of vasodilators (intravenous
      Prostaglandin (PGI2) (0.5-1 ng/kg/min), inhaled   nitric oxide  (10-40 ppm), 
      dopamine (2 mcg/kg/min) and vasopressors (intravenous dobutamine (5-15
      mcg/kg/min), norepinephrine (0.05-1 mcg/kg/min),ephedrine (5 to 10 mg bolus doses
      ) to keep mean arterial blood pressure above 50 mmHg. RESULTS: Cardiopulmonary
      bypass (CPB) was performed in five patients who underwent sequential BLT and one
      SLT case. Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) was used
      in four cases of sequential BLT and in two cases of SLT. Neither ECMO nor CPB was
      performed in two BLT and in one SLT patient. One SLT patient who underwent CPB
      was admitted to the intensive care unit with support of intra-aortic balloon pump
      (IABP) and ECMO. Intraoperative death did not occur. CONCLUSION: During SLT or
      BLT, management of anesthesia with propofol and remifentanil provides a stable
      hemodynamic and medical support. Although our experience with VA ECMO was
      limited, our experience shows that this support system is a valuable tool to
      provide hemodynamic stability for patients undergoing LT.

PMID- 27041522
TI  - Positive Correlation of Serum Adiponectin with Lipid Profile in Patients with
      Type 2 Diabetes Mellitus is Affected by Metabolic Syndrome Status.
AB  - BACKGROUND: Type-2 diabetes mellitus (DM) and Metabolic syndrome (MetS) are both
      associated with dyslipidemia which may lead to development of vascular
      complications. Adiponectin is an anti-inflammatory protein synthesized by the
      adipose tissue. There is controversy regarding the association of adiponectin
      with lipid profile. AIM: To evaluate the correlation between serum adiponectin
      concentration and metabolic profile in patients with type-2 DM. METHODS: A single
      center cross-sectional study was conducted on 173 patients with type-2 DM (82
      males and 91 females). Plasma adiponectin concentration, lipid profile, glucose
      profile, and anthropometric features were investigated. Insulin resistance was
      determined using Homeostasis model assessment (HOMA). Correlation of serum
      adiponectin with lipid profile of patients with type-2 DM was assessed. RESULTS:
      Adiponectin was negatively correlated with waist circumference (r = -0.16, P =
      0.06) and positively with HbA1c (r = 0.19, P = 0.032), total cholesterol (r =
      0.23, P = 0.017), LDL (r = 0.30, P = 0.001), SD-LDL (r = 0.41, P < 0.001), and SD
      LDL/LDL (r = 0.22, P = 0.023). We found a positive correlation between
      adiponectin and total cholesterol (r = 0.27, P = 0.055), LDL (r = 0.34, P =
      0.026) and SD-LDL (r = 0.41, P = 0.006) in patients with at least 3 components of
      MetS criteria. Correlation of adiponectin with LDL and SD-LDL remained positively
      significant with increasing the number of MetS components. In patients with 5
      components of MetS, serum adiponectin was significantly correlated with serum
      triglyceride (r = 0.89). Significant interaction was observed between adiponectin
      and metabolic syndrome in relation to serum lipid profile. CONCLUSION: The
      results of the present study suggest that in patients with type-2 DM and MetS,
      lipid profile is strongly correlated with blood concentration of adiponectin. The
      strongest association was observed between serum adiponectin and LDL.

PMID- 27041523
TI  - A Role for Heterozygosity of NF-??B1 rs28362491 Polymorphism in Patients with
      Idiopathic Oligospermia.
AB  - BACKGROUND: Nuclear factor-kappa B (NF-??B) activation and its inhibition by NF
      ??B inhibitor (I??B) have been functionally linked to germ cell apoptosis, which
      may affect human infertility. We hypothesized a possible relationship between the
      NF-??B1-94ins/del ATTG (rs28362491) and NF-??BIA 3'UTR A->G (rs696) polymorphism,
      which are common polymorphisms and the susceptibility to oligospermia in the
      context of the sperm apoptosis. METHODS: In order to evaluate this association,
      we studied the polymorphisms and sperm apoptosis rates of 114 men with idiopathic
      oligospermia, as well as 130 normospermic men, using PCR-RFLP and TUNEL staining
      methods, respectively. RESULTS: Univariate analysis revealed that heterozygous ID
      genotype at the NF-??B1 -94ins/del ATTG polymorphism is associated with an
      approximately 2.4-fold reduced risk of oligospermia (P = 0.006, 95% confidence
      intervall = 1.34 - 4.13). However, the genotype and allele frequencies of NF
      ??BIA 3'UTR A->G polymorphism, and the genotype frequencies of all possible
      rs28362491/rs696 genotype combinations did not show any significant differences
      between oligospermic and normospermic men. Furthermore, neither polymorphism
      appeared to affect sperm apoptosis, although the sperm apoptosis index was
      detected to be significantly higher in the oligospermic patients compared with
      those in the controls (P < 0.05). CONCLUSION: Our findings suggested that the
      heterozygosity of rs28362491 in the NF-??B1 gene may have a protective effect
      against oligospermia and could modify the susceptibility of oligospermia in a
      group with idiopathic male infertility in a Turkish population.

PMID- 27041524
TI  - Effects of Synbiotics Supplementation in Lean Patients with Nonalcoholic Fatty
      Liver Disease: Study Protocol of a Pilot Randomized Double-blind Clinical Trial.
AB  - INTRODUCTION: Currently, Nonalcoholic Fatty Liver Disease (NAFLD) is the most
      common liver disease in the world. The only approved treatment for it is
      lifestyle modification and weight loss; however, there is no treatment option for
      patients with normal or low body mass index (BMI). The aim of this study is to
      evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal
      or low BMI. METHODS AND ANALYSIS: In our randomized, double-blind, placebo
      controlled clinical trial protocol, forty-two patients will be assigned to take
      either a synbiotic or a placebo capsule for 28 weeks. Both groups will undergo
      the standard treatment. ETHICS AND DISSEMINATION: The study protocol has been
      approved by ethics committee of Shahid Beheshti University of Medical Sciences.
      At the beginning of the study, a written informed consent form will be signed and
      dated by subjects and investigators. The results will be published in due time.

PMID- 27041525
TI  - Anatomic Anomalies Encountered in 467 Open Carpal Tunnel Surgeries.
AB  - Carpal tunnel syndrome is the most common compression neuropathy and carpal
      tunnel surgery is the most frequently performed hand surgery. Anatomic anomalies
      may predispose the median nerve to compression. The aim of the current study was
      to search for anatomic anomalies in open carpal tunnel surgeries through a cross
      sectional study. During a cross-sectional study in a one-year period, 436
      consecutive patients (307 females and 129 males) with the average age of 50.3 +/-
      2.4 years underwent 467 classic open carpal tunnel surgeries. Thirty-one patients
      had bilateral surgeries. A thorough inspection of the incisions was conducted to
      search for vascular, neural, tendon and muscular anomalies. Forty-two (8.9%)
      hands (14 males and 28 females) had anomalies. The average age of the patients
      with discovered anomalies was 48.6 +/- 7.6 years. Ten anomalies were seen on the
      left hands and 32 anomalies were seen on the right hands. Among the 42 anomalies,
      there were 16 persistent median arteries, 14 anomalies of the median nerve, 7
      intratunnel intrusion of the flexor and lumbrical muscle bellies and 5 anomalies
      of the origin of the thenar muscles. There was no correlation between the
      discovered anomalies and the age, gender or hand sides. Anatomical anomalies are
      not uncommon in carpal tunnel surgeries. However, the frequencies of the reported
      anomalies vary among different studies. Familiarity with these anomalies
      increases the safety of the operation.

PMID- 27041526
TI  - Prevalence of Food Insecurity in Iran: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Food security is one of the main factors of individual and social
      health. It is of such importance that the World Bank and Food and Agriculture
      Organization (FAO) announced it as one of the Millennium Development Goals. This
      study aimed to report the prevalence of food insecurity in Iran. METHODS: We
      searched English databases including; Scopus, Ovid, Web of Science, PubMed and
      Google Scholar and also Iranian databases; SID, Magiran and IranMedex for words
      Iran, food insecurity, and prevalence up to August 2015. The pooled food
      insecurity prevalence was calculated using Der-Simonian test. All analyses were
      performed using random effects model with 95% CI. We assessed heterogeneity of
      the studies using sub-group and meta-regression analyses. RESULTS: A total of 31
      studies were included. The prevalence of food insecurity was 49% among households
      (95% CI: %40-%59), 67% in children (95% CI: %63-%70), 61% in mothers (95% CI: %35
      %88), 49% in adolescents (95% CI: %33-%66) and 65% in the elderly (95% CI: %44
      %86). CONCLUSION: The prevalence of food insecurity is high in Iran. Fiscal
      policies should promote the nutritional knowledge of household members and also
      support the households to meet their nutritional needs. This plan should give
      priority to mid and low socioeconomic groups.

PMID- 27041527
TI  - Photoclinic.

PMID- 27041528
TI  - MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of
      the Colon.
AB  - Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal
      disease. The most common extranodal site is the gastrointestinal tract (GI), with
      the stomach most frequently involved, followed by the small bowel. Primary DLBCL
      of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two
      patients who underwent radical resections of right colonic tumors. They were
      diagnosed with primary colonic DLBCL following histological and
      immunohistochemical testing of the excised tissues, and were determined as being
      in stage IIE of the disease. The tumors expressed CD20 markers. Both received
      multi-agent chemotherapy with combined immunotherapy and remain in complete
      remission at 4 and 5 years. 

PMID- 27041529
TI  - Borzuyeh e Tabib (The Iranian Physician).

PMID- 27041530
TI  - The 3rd International Congress on Transfusion Medicine Tehran, Iran.

PMID- 27041531
TI  - The Knowledge without Border.

PMID- 27041532
TI  - The Impact of Ramadhan Fasting in Women with PCOS: an Association Between FPG and
      Lipid Profiles.

PMID- 27041533
TI  - Professor Jamal Gousheh, 1931-2016.

PMID- 27041534
TI  - Methadone treatment, bruxism, and temporomandibular disorders among male
      prisoners.
AB  - There is little information on bruxism related to illicit drug use. Prolonged
      drug use may damage the stomatognathic system via oral motor overactivity. The
      aim of the present study was to compare the rates of bruxism and
      temporomandibular disorders (TMDs) between prisoners with and without drug-use
      disorders, to evaluate the association between methadone treatment and bruxism
      and to assess the possible relationship between bruxism and pain. The sample
      included 152 male prisoners, 69 of whom were drug users maintained on methadone.
      All prisoners were examined by an experienced dentist and completed a
      questionnaire on their oral habits, with the aim of detecting signs or symptoms
      of TMD and/or bruxism. Additional data were collected from medical files. The
      prevalence of sleep bruxism and awake bruxism, but not of TMDs, was significantly
      higher among drug-user than non-drug user prisoners (52.2% vs. 34.9% for sleep
      bruxism, 59.7% vs. 30.1% for awake bruxism, and 46.3% vs. 25.6% for TMDs,
      respectively). Participants with awake bruxism were statistically more sensitive
      to muscle palpation compared with participants with sleep bruxism [rating scores
      (mean +/- SD): 0.32 +/- 0.21 vs. 0.19 +/- 0.28, respectively]. An association was
      found between sleep bruxism and awake bruxism. It seems that there is a direct or
      an indirect association between methadone maintenance treatment and sleep bruxism
      or awake bruxism in male prisoners.

PMID- 27041535
TI  - Erratum to: Quantifying the legacy of the Chinese Neolithic on the maternal
      genetic heritage of Taiwan and Island Southeast Asia.
AB  - In the original article, one of the co-authors' (Ken Khong Eng) given name has
      been published incorrectly. The correct given name should be Ken Khong. The
      original article has been corrected.

PMID- 27041536
TI  - Effects of inter- and intra-aggregate magnetic dipolar interactions on the
      magnetic heating efficiency of iron oxide nanoparticles.
AB  - Iron oxide nanoparticles have found an increasing number of biomedical
      applications as sensing or trapping platforms and therapeutic and/or diagnostic
      agents. Most of these applications are based on their magnetic properties, which
      may vary depending on the nanoparticle aggregation state and/or concentration. In
      this work, we assess the effect of the inter- and intra-aggregate magnetic
      dipolar interactions on the heat dissipation power and AC hysteresis loops upon
      increasing the nanoparticle concentration and the hydrodynamic aggregate size. We
      observe different effects produced by inter- (long distance) and intra-aggregate
      (short distance) interactions, resulting in magnetizing and demagnetizing
      effects, respectively. Consequently, the heat dissipation power under alternating
      magnetic fields strongly reflects such different interacting phenomena. The intra
      aggregate interaction results were successfully modeled by numerical simulations.
      A better understanding of magnetic dipolar interactions is mandatory for
      achieving a reliable magnetic hyperthermia response when nanoparticles are
      located into biological matrices. 

PMID- 27041537
TI  - Classification of healthcare systems: Can we go further?
AB  - This article addresses the issue of the classification of healthcare systems,
      with the intent to take a step further than the previously analysed models of
      healthcare organisation. As concerns the financing of healthcare services, the
      standard tripartite classification (according to which healthcare systems are
      divided into three groups: voluntary insurance, social health insurance and
      universal coverage) is enriched with two additional types: compulsory national
      health insurance and residual programs. With respect to the provision of services
      and the relationship between insurers and providers, it is important to
      distinguish between vertically integrated and separated systems. What
      differentiates this analysis from the majority of previous studies is its
      underlying logic. Assuming that all systems are hybrid, the article proposes to
      put aside the classic logic for classifying healthcare systems (according to
      which individual countries are pigeonholed into different classes depending on
      the prevailing system) in favour of the identikit logic. The concept of
      segmentation (of healthcare services or population) proves to be remarkably
      useful to this purpose. 

PMID- 27041538
TI  - Oxcarbazepine-induced liver injury after sensitization by valproic acid: a case
      report.
AB  - OBJECTIVE: The aim of the present case report is to describe a potential
      interaction between valproic acid and oxcarbazepine that resulted in hepatic
      injury. METHODS: We report the case of a 46-year-old man with schizoaffective
      disorder who was cross-titrated from valproic acid to oxcarbazepine because of
      liver injury. RESULTS: Initiation of oxcarbazepine four days after stopping
      valproic acid produced a significant elevation in liver enzymes that normalized
      with oxcarbazepine discontinuation and did not reappear with its reintroduction
      five days later. CONCLUSIONS: Our findings suggest that a longer washout period
      or another agent should be considered when transitioning from valproic acid to
      oxcarbazepine.

PMID- 27041539
TI  - Defective support network: a major obstacle to coping for patients with heart
      failure: a qualitative study.
AB  - BACKGROUND: Heart failure as a chronic disease poses many challenges for a
      patient in his or her everyday life. Support in various aspects of life
      positively affects coping strategies and influences the well-being and health
      outcomes of heart failure patients. Inadequate support may lead to a worsening of
      symptoms, increased hospital readmissions, psychological disorders, and a reduced
      quality of life. OBJECTIVE: This study explored obstacles to coping related to
      support for heart failure patients as viewed by the patients themselves and their
      family members and caregivers. DESIGN: This qualitative study was conducted using
      content analysis. The 20 Iranian participants included 11 patients with heart
      failure, three cardiologists, three nurses, and three family members of heart
      failure patients selected through purposive sampling. Data were collected through
      semi-structured interviews and analyzed using the Lundman and Graneheim
      qualitative content analysis method. RESULTS: During data analysis, 'defective
      support network' developed as the main theme along with four other categories of
      'inadequate family performance', 'inadequate support by the healthcare team',
      'distorted societal social support', and 'inadequate welfare support'.
      CONCLUSION: The findings of the current study can assist health authorities and
      planners in identifying the needs of patients with heart failure so as to focus
      and plan on facilitating their coping as much as possible by obviating the
      existing obstacles.

PMID- 27041543
TI  - Perineural Injection of the Ethmoidal Nerve of Horses.
AB  - OBJECTIVE: To describe the anatomical location of the ethmoidal nerve in the
      equine periorbital region and to determine the accuracy of a technique used to
      deposit local anesthetic solution adjacent to the nerve. STUDY DESIGN:
      Prospective experimental study. ANIMALS: Adult equine cadaver heads (n=6 for
      preliminary dissection; n=15 [30 nerve sites] for evaluation of injection
      technique). METHODS: Preliminary dissections were performed to identify landmarks
      for injection of local anesthetic adjacent to the ethmoidal nerve. For evaluation
      of the injection technique a 20 gauge 6 cm spinal needle was inserted into the
      rostromedial aspect of the supraorbital fossa, where the caudal aspect of the
      zygomatic process emerges from the frontal bone caudal and medial to the globe.
      The needle was inserted to its hub at an angle of 110 degrees  to the long axis
      of the head using a protractor, in both a sagittal plane and a transverse plane,
      and 0.5 mL of new methylene blue dye was injected as a marker. The ethmoidal
      nerve was identified by dissection immediately after each injection and inspected
      for proximity of the dye. RESULTS: Dye was observed surrounding the nerve in 27
      of 30 sites (90%) or lying within 5 mm of the nerve at the other 3 sites.
      CONCLUSION: The described technique of perineural injection of the ethmoidal
      nerve proved reliable and simple. Anesthetizing the ethmoidal nerve may be
      helpful in desensitizing portions of the ipsilateral paranasal sinuses and nasal
      cavity innervated by the nerve when sinonasal surgery is performed in the
      standing horse.

PMID- 27041544
TI  - Epiretinal membrane surgery evaluated by subjective outcome.
AB  - PURPOSE: To examine pre- and postoperative visual interference, subjective
      symptoms and visual acuity in patients undergoing epiretinal membrane (ERM)
      surgery. METHODS: A retrospective observational case series comparing 239 eyes in
      231 consecutive patients with idiopathic ERM in a selected catchment area from
      2002 to 2009. Demography, visual acuity (VA), lens status and subjective symptoms
      were analysed before and after the operation. Patients, healthy enough to
      participate at least 2 years post surgery, answered a questionnaire about their
      subjective functional impairment before and after the ERM peeling. Visual
      disturbance was assessed on a visual analogue scale (VAS) ranging from 1 to 100
      mm. RESULTS: The preoperative VA for the eyes in the study was median 0.40 logMAR
      (logarithm of the minimum angle of resolution) (range -0.1 to 1.22) resulted in
      VA of 0.22 logMAR (range -0.1 to 1.1), which is a statistical significant
      difference (p -). Of 180 patients contacted, answers were received from 103
      (57%). Subjective visual disturbance assessed on the VAS showed a median of 70 mm
      (range 0-100) before surgery compared to a subjective disturbance median 27 mm
      (range 0-98) postoperatively. The change preoperatively to postoperatively was
      mean -34 mm (SD 31), median -37 (range -96 to 37), p -. Patients with much
      disturbance at baseline measured by VAS experienced more subjective benefit of
      the operation measured by the distance between the mark on the VAS preoperatively
      and postoperatively, p -, Spearman correlation coefficient. CONCLUSION: Patients
      with considerable preoperative disturbance benefit more from an operation than
      those with less disturbance.

PMID- 27041545
TI  - Emotional manifestations of PD: Neurobiological basis.
AB  - Neuropsychiatric symptoms are common and disabling in PD. Their neurobiological
      bases are complex, partly because of the disease itself and partly because of the
      dopaminergic treatment. The aim of this review is to focus on the emotional
      manifestations stemming from the neurodegenerative process itself. We focus on
      depression, anxiety, apathy, and fatigue, which can all be part of the clinical
      spectrum of premotor disease and may be improved or masked by medications
      targeting parkinsonian motor signs or psychiatric symptoms as the disease
      progresses. Findings from clinical, neuroimaging, and animal studies are
      reviewed, showing a major contribution of the dopaminergic system to the
      pathophysiology of these disabling symptoms. Degeneration of noradrenergic and
      serotonergic projection systems also has an impact on psychiatric symptoms of PD.
      The available literature is reviewed, but at present there is a lack of studies
      that would allow disentangling the separate contribution of each of the
      monoaminergic systems. The use of a pragmatic classification of all these
      symptoms under the umbrella of hypodopaminergic behavioral syndrome seems
      clinically useful, as it emphasizes the crucial, although not exclusive, nature
      of their dopaminergic neurobiological basis, which has important implications in
      the clinical management of PD. (c) 2016 International Parkinson and Movement
      Disorder Society.

PMID- 27041546
TI  - Pachyonychia Congenita: A Spectrum of KRT6a Mutations in Australian Patients.
AB  - BACKGROUND: Pachyonychia congenita (PC) is a rare inherited disorder of
      keratinization characterised by hypertrophic nail dystrophy, painful palmoplantar
      blisters, cysts, follicular hyperkeratosis and oral leukokeratosis. It is
      associated with mutations in five differentiation-specific keratin genes, KRT6A,
      KRT6B, KRT6C, KRT16, or KRT17. OBJECTIVES: Living with Pachyonychia Congenita can
      be isolating. The aim of this paper is to document a single patient's experience
      within a national context. METHOD: We report the case of a 2 year old female with
      an atypical presentation of PC due to a mutation in KRT6A with severely
      hypertrophic follicular keratoses, skin fragility, relative sparing of nail
      hypertrophy on one hand and failure to thrive in early infancy. In collaboration
      with the International Pachyonychia Congenita Research Registry (IPCRR), a
      database search was performed using Australian residency and KRT6A mutation as
      inclusion criteria. The IPCRR database was also searched for a matching KRT6A
      mutation. Six Australian patients were identified in addition to one patient with
      an identical mutation residing in the United States. The detailed standardized
      patient questionnaire data was manually collated and analysed. RESULTS:
      Fingernail hypertrophy and oral leukokeratosis were the most common features.
      There was no recording of asymmetric distribution in any other Australian
      patient. Trouble nursing as an infant and follicular hyperkeratosis also occurred
      in the American patient, however they did not have asymmetric distribution and
      the oral leukokeratosis appeared later in life. CONCLUSION: This case has unique
      features. Sharing information can assist patients navigating life with this
      condition.

PMID- 27041547
TI  - Evidence for Tunisian-Like Pestiviruses Presence in Small Ruminants in Italy
      Since 2007.
AB  - The genus Pestivirus, which belongs to the Flaviviridae family, includes ssRNA+
      viruses responsible for infectious diseases in pigs, cattle, sheep, goats and
      other domestic and wild ruminants. Like most of the RNA viruses, pestivirus has
      high genome variability with practical consequences on disease epidemiology,
      diagnosis and control. In addition to the officially recognized species in the
      genus Pestivirus, such as BVDV-1, BVDV-2, BDV and CSFV, other pestiviruses have
      been detected. Furthermore, most of the ruminant pestiviruses show low or absent
      species specificity observed in serological tests and are able to infect multiple
      species. Particularly, small ruminants are receptive hosts of the most
      heterogeneous group of pestiviruses. The aim of this study was to carry out the
      molecular characterization of pestiviruses isolated from sheep and goats in
      Sicily, Italy. Phylogenetic analysis of two viral genomic regions (a fragment of
      5'-UTR and the whole Npro regions) revealed the presence of different pestivirus
      genotypes in the analysed goat and sheep herds. Two of five viral isolates were
      clustered with BVDV-1d viruses, a strain widespread in Italy, but never reported
      in Sicily. The other three isolates formed a distinct cluster with high
      similarity to Tunisian isolates, recently proposed as a new pestivirus species.
      This represents the first evidence for Tunisian-like pestivirus presence in small
      ruminants in Italy. Furthermore, one of the isolates was collected from a goat,
      representing the first isolation of Tunisian-like pestivirus from this species.

PMID- 27041548
TI  - Induction Immunosuppression in High-risk Kidney Transplant Recipients.
AB  - Kidney transplant remains the best type of renal replacement therapy in most
      patients with end-stage kidney disease, even in those with high immunologic risk.
      Immunosuppression in these patients is regarded as more complex, owing to the
      higher risk of both acute and chronic rejection. The advent of induction
      immunosuppression has resulted in a lower incidence of acute rejection and
      consequently improved short-term patient and allograft outcomes. Indeed, the use
      of these agents, especially in high-risk recipients, has become standard of care
      at most transplant centers. Transplant physicians are constantly faced with the
      challenge of estimating the recipients' immunologic risk and tailoring their
      immunosuppression accordingly. This review article aims to provide an up-to-date
      evaluation of the various studies available, which investigated the use of
      induction agents in kidney transplant, specifically in high-risk recipients. It
      evaluates the use of the most frequently used polyclonal antibody (rabbit
      antithymocyte globulin) versus the less commonly used monoclonal antibody
      alemtuzumab, superseded agents such as muromonab-CD3, and potentially emerging
      agents such as rituximab, bortezomib, and eculizumab. With this systematic
      review, we hope to inform the scientific community and facilitate this
      controversial decision through the implementation of robust scientific evidence. 

PMID- 27041549
TI  - Correlation of Wnt and NOTCH pathways in esophageal squamous cell carcinoma.
AB  - There is an inevitable association between cell signaling pathways and
      tumorigenesis. Wnt and notch pathways play important roles during development and
      self-renewal. Beside the independent role of such pathways on tumor progression,
      different cross talks between these pathways through tumorigenesis are
      emphasized. In this study, we analyzed cross talk between Wnt and NOTCH signaling
      pathways through assessment of probable correlation between MAML1 and PYGO2 as
      the main transcription factors of these pathways, respectively in esophageal
      squamous cell carcinoma (ESCC) patients. Levels of MAML1 and PYGO2 mRNA
      expression in 48 ESCC patients were compared to the correlated margin normal
      tissues using real-time polymerase chain reaction (PCR). Eleven out of 48
      patients (22.9 %) have shown the concomitant MAML1/PYGO2 over expression in
      significant correlation with tumor size (p = 0.046) and depth of tumor invasion
      (p = 0.050). We showed that there is a significant correlation and feedback
      between these markers during the ESCC progression and metastasis. 

PMID- 27041550
TI  - W. Elwood Briles 1918-2016.

PMID- 27041551
TI  - Maxillary molar distalization with aligners in adult patients: a multicenter
      retrospective study.
AB  - BACKGROUND: The aim of the present study was to test the hypothesis that bodily
      maxillary molar distalization was not achievable in aligner orthodontics.
      METHODS: Forty lateral cephalograms obtained from 20 non-growing subjects (9
      male, 11 female; average age 29.73 years) (group S), who underwent bilateral
      distalization of their maxillary dentition with Invisalign aligners (Align
      Technology, Inc., San Jose, CA, USA), were considered for the study. Skeletal
      class I or class II malocclusion and a bilateral end-to-end class II molar
      relationship were the main inclusion criteria. Cephalograms were taken at two
      time points: (T0) pretreatment and (T2) post-treatment. Treatment changes were
      evaluated between the time points using 39 variables by means of paired t test.
      The level of significance was set at P < 0.05. Reproducibility of measurements
      was assessed by the intraclass correlation coefficient (ICC). RESULTS: The mean
      treatment time was 24.3 +/- 4.2 months. At the post-treatment point, the first
      molar moved distally 2.25 mm without significant tipping (P = 0.27) and vertical
      movements (P = 0.43). The second molar distalization was 2.52 mm without
      significant tipping (P = 0.056) and vertical movements (P = 0.25). No significant
      movements were detected on the lower arch. SN^GoGn and SPP^GoGn angles showed no
      significant differences between pre- and post-treatment cephalograms (P = 0.22
      and P = 0.85, respectively). CONCLUSIONS: Aligner therapy in association with
      composite attachments and class II elastics can distalize maxillary first molars
      by 2.25 mm without significant tipping and vertical movements of the crown. No
      changes to the facial height were revealed.

PMID- 27041552
TI  - Synthesis of 1,4-disubstituted 1,2,3-triazole Derivatives Using Click Chemistry
      and their Src Kinase Activities.
AB  - BACKGROUND: Tyrosine kinases (TK) are enzymes that catalyze the phosphorylation
      of tyrosine residues on proteins by the transfer of phosphate moiety of ATP. TK
      are key regulators of various cell functions, such as cellular growth,
      proliferation, migration, differentiation, and apoptosis. Src mutations and/or
      overexpression has been correlated with tumor growth, metastasis, and
      angiogenesis [4,5]. Thus, the design and the discovery of novel Src kinase
      inhibitors remains critically important. METHODS: A series of 1,4-disubstituted
      1,2,3-triazoles derivatives were designed and prepared as potential inhibitors
      for Src kinase. In this manuscript, all of the designed compounds were screened
      via molecular docking using PLANTS as virtual screening software to identify new
      inhibitors of Src kinase. Subsequently, all of the screened compounds were
      synthesized via Huisgen's 1,3-dipolar cycloaddition between terminal alkynes (1)
      and methyl 2-azidoacetate (2) with Cu(I) in excellent yields at room temperature.
      RESULTS: In the present study, we report the design and the synthesis of a series
      of 1,4-disubstituted 1,2,3-triazoles involving one pot condensation of methyl 2
      azidoacetate and different terminal alkynes. All the synthesized triazoles were
      characterized by IR, 1 H, 13 C, 19 F NMR, and HRMS. They were investigated as
      inhibitors of Src kinase. CONCLUSION: A series of 1,4-disubstituted 1,2,3
      triazole compounds were synthesized through an easy, convenient Cu(I) catalyzed
      click reaction and evaluated for their Src kinase activity. Compound 3m exhibited
      significant inhibitory activity against Src Kinase. These results, along with
      molecular design docking observations, are significant evidence to demonstrate
      the compound 3m could be optimized as a potential Src kinase inhibitor in further
      studies.

PMID- 27041553
TI  - Synergistic Effect of the Combination of Novel Suberoylanilide Hydroxamic Acid
      Derivatives with Cisplatin on Anti-proliferation of Human Cancer Cells.
AB  - A novel, green, and atom-economical boric acid catalyzed direct amidation without
      the use of any coupling agents for the preparation of suberoylanilide hydroxamic
      acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer
      cells is provided. The new SAHA-based inhibitor B123, when used alone, exhibited
      higher anti-proliferative activities than SAHA or Cisplatin against a number of
      human cancer cells. We have examined the effect of combination of these SAHA
      based inhibitors with Cisplatin. We found synergistic effects of the combination
      of SAHA-based inhibitors with Cisplatin over a wide range of concentrations
      against human liver cancer cells HepG2 and two human lung cancer cell lines H1299
      and H460. This synergism leads up to 8-fold of dose reduction for Cisplatin in
      the combination with our synthesized inhibitor B123 against H1299.

PMID- 27041554
TI  - Hyperbaric oxygen therapy improves colorectal anastomotic healing.
AB  - PURPOSE: Hyperbaric oxygen treatment (HBOT) has been found to improve the healing
      of poorly oxygenated tissues. This study aimed to investigate the influence of
      HBOT on the healing in ischemic colorectal anastomosis. METHODS: Forty Wistar
      rats were randomly divided into a treatment group that received HBOT for 10
      consecutive days (7 days before and 3 days after surgery), or in a control group,
      which did not receive the therapy. Colectomy with an ischemic anastomosis was
      performed in all rats. In each group, the rats were followed for 3 or 7 days
      after surgery to determine the influence of HBOT on anastomotic healing. RESULTS:
      Five rats from each group died during follow-up. No anastomotic dehiscence was
      seen in the HBOT group, compared to 37.5 % and 28.6 % dehiscence in the control
      group on postoperative day (POD) 3 and 7, respectively. The HBOT group had a
      significantly higher bursting pressure (130.9 +/- 17.0 mmHg) than the control
      group (88.4 +/- 46.7 mmHg; p = 0.03) on POD 3. On POD 3 and POD 7, the adhesion
      severity was significantly higher in the control groups than in the HBOT groups
      (p < 0.005). Kidney function (creatinine level) of the HBOT group was
      significantly better than of the control group on POD 7 (p = 0.001).
      Interestingly, a significantly higher number of CD206+ cells (marker for type 2
      macrophages) was observed in the HBOT group at the anastomotic area on POD 3.
      CONCLUSION: Hyperbaric oxygen enhanced the healing of ischemic anastomoses in
      rats and improved the postoperative kidney function.

PMID- 27041555
TI  - Laparoscopic ventral mesh rectopexy in complex pelvic floor disorder.
AB  - AIM: For the treatment of complex pelvic organ prolapse, many different surgical
      procedures are described without any comparative studies available. Laparoscopic
      ventral mesh rectopexy after D'Hoore is one of the methods, which is publicized
      to treat patients with symptomatic rectocele, enterocele and rectal prolapse.
      METHOD: All patients who received ventral mesh rectopexy since 07/10 for
      symptomatic rectocele, enterocele and possible rectal prolapse I  degrees  or II 
      degrees  in terms of a complex pelvic floor disorder were included in this follow
      up study. The Wexner score for incontinence was recorded (range 0-20), the
      constipation score of Herold (r6-30) was evaluated as well as supplementary
      questions compiled by D'Hoore concerning outlet symptoms (r0-20). In addition,
      the quality of life (SF-12) was requested. RESULTS: Thirty-one women were
      operated in the period, and 27 were eligible to be included in the present study.
      Median follow-up was 22 months (2-39). The preoperative Wexner score was in
      median 8 (0-20), going down to 6 (0-20) without significance (p = 0.735). The
      constipation score decreased significantly from median 14 (9-21) to 11 (6-25) (p
      = 0.007). The median score after D'Hoore was preoperatively 8 (4-16) and 4.5 (0
      17) postoperatively (p = 0.004). The SF-12 values were preoperatively
      significantly reduced compared to the normal population; postoperatively, they
      equalized. CONCLUSION: Two years after laparoscopic ventral mesh rectopexy,
      constipation and quality of life improve significantly in patients with complex
      pelvic organ prolapse. The grade of incontinence remains essentially the same,
      but was not the dominant clinical problem in the treated patients of our study.
      STATEMENT: The improvement in constipation and quality of life after laparoscopic
      ventral mesh rectopexy for obstructive defecation is encouraging. However, the
      impact on sexual life differs; some patients improve but a relevant number
      reports a change for the worse.

PMID- 27041556
TI  - Witnessing the first sign of retinitis pigmentosa onset in the allegedly normal
      eye of a case of unilateral RP: a 30-year follow-up.
AB  - PURPOSE: A patient initially presented with constricted visual field, attenuated
      retinal vasculature, pigmentary clumping and reduced ERG in OS only, suggestive
      of unilateral retinitis pigmentosa (RP). This patient was subsequently seen on
      eight occasions (over three decades), and, with time, the initially normal eye
      (OD) gradually showed signs of RP-like degeneration. The purpose of this study
      was to evaluate which clinical modality (visual field, funduscopy or
      electroretinography) could have first predicted this fate. METHODS: At each time
      points, data obtained from our patient were compared to normative data using Z
      tests. RESULTS: At initial visit, all tests were significantly (p < 0.05) altered
      in OS and normal in OD. Visual field and retinal vessel diameter in OD reduced
      gradually to reach statistical significance at the 5th visit and 6th visit (21
      and 22 years after the first examination, respectively). In OD, the amplitude of
      the scotopic and photopic ERGs reduced gradually and was significantly smaller
      than normal at the 2nd visit (after 11 years) and 3rd visit (after 18 years),
      respectively. When the photopic ERG was analyzed using the discrete wavelet
      transform (DWT), we were able to detect a significant change at the 2nd visit
      (after 11 years) instead of the 3rd visit (18 years). CONCLUSIONS: Our study
      allowed us to witness the earliest manifestation of an RP disease process. The
      ERG was the first test to detect significant RP changes. A significantly earlier
      detection of ERG anomalies was obtained when the DWT was used, demonstrating its
      advantage for early detection of ERG changes.

PMID- 27041557
TI  - [Not Available].

PMID- 27041559
TI  - Evolution of the nation's blood supply system.

PMID- 27041560
TI  - Targeting CK2-driven non-oncogene addiction in B-cell tumors.
AB  - Genetic mutations of oncogenes often underlie deranged cell growth and altered
      differentiation pathways leading to malignant transformation of B-lymphocytes.
      However, addiction to oncogenes is not the only drive to lymphoid tumor
      pathogenesis. Dependence on non-oncogenes, which act by propelling basic
      mechanisms of cell proliferation and survival, has also been recognized in the
      pathobiology of lymphoid leukemias, lymphomas and multiple myeloma. Among the
      growing number of molecules that may uphold non-oncogene addiction, a key place
      is increasingly being recognized to the serine-threonine kinase CK2. This enzyme
      is overexpressed and overactive in B-acute lymphoblastic leukemia, multiple
      myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphomas, such as mantle
      cell, follicular, Burkitt's and diffuse large B-cell lymphomas. In these tumors,
      CK2 may serve the activity of oncogenes, similar to BCR-ABL and c-MYC, control
      the activation of critical signaling cascades, such as NF-kappaB (nuclear factor
      kappaB), STAT3 (signal transducer and activator of transcription 3) and
      PTEN/PI3K/AKT (phosphatase and tensin homolog protein/phosphoinositide 3
      kinase/AKR thymoma), and sustain multiple cellular stress-elicited pathways, such
      as the proteotoxic stress, unfolded protein and DNA-damage responses. CK2 has
      also been shown to have an essential role in tuning signals derived from the
      stromal tumor microenvironment. Not surprisingly, targeting CK2 in lymphoid tumor
      cell lines or mouse xenograft models can boost the cytotoxic effects of both
      conventional chemotherapeutics and novel agents, similar to heat-shock protein
      90, proteasome and tyrosine kinases inhibitors. In this review, we summarize the
      evidence indicating how CK2 embodies most of the features of a cancer growth
      promoting non-oncogene, focusing on lymphoid tumors. We further discuss the
      preclinical data of the use of small ATP-competitive CK2 inhibitors, which hold
      the promise to be additional options in novel drug combinations for the therapy
      of lymphoid and plasmacellular malignancies.

PMID- 27041561
TI  - RSK2 signals through stathmin to promote microtubule dynamics and tumor
      metastasis.
AB  - Metastasis is responsible for >90% of cancer-related deaths. Complex signaling in
      cancer cells orchestrates the progression from a primary to a metastatic cancer.
      However, the mechanisms of these cellular changes remain elusive. We previously
      demonstrated that p90 ribosomal S6 kinase 2 (RSK2) promotes tumor metastasis.
      Here we investigated the role of RSK2 in the regulation of microtubule dynamics
      and its potential implication in cancer cell invasion and tumor metastasis.
      Stable knockdown of RSK2 disrupted microtubule stability and decreased
      phosphorylation of stathmin, a microtubule-destabilizing protein, at serine 16 in
      metastatic human cancer cells. We found that RSK2 directly binds and
      phosphorylates stathmin at the leading edge of cancer cells. Phosphorylation of
      stathmin by RSK2 reduced stathmin-mediated microtubule depolymerization.
      Moreover, overexpression of phospho-mimetic mutant stathmin S16D significantly
      rescued the decreased invasive and metastatic potential mediated by RSK2
      knockdown in vitro and in vivo. Furthermore, stathmin phosphorylation positively
      correlated with RSK2 expression and metastatic cancer progression in primary
      patient tumor samples. Our finding demonstrates that RSK2 directly phosphorylates
      stathmin and regulates microtubule polymerization to provide a pro-invasive and
      pro-metastatic advantage to cancer cells. Therefore, the RSK2-stathmin pathway
      represents a promising therapeutic target and a prognostic marker for metastatic
      human cancers.

PMID- 27041562
TI  - KLF13 regulates the differentiation-dependent human papillomavirus life cycle in
      keratinocytes through STAT5 and IL-8.
AB  - High-risk strains of human papillomavirus (HPV) are the causative agents of
      cervical and anogenital cancers and are associated with 5% of all human cancers.
      Although prophylactic vaccines targeting a subset of HPV types are available,
      they are ineffective in HPV-infected individuals. Elucidation of the mechanisms
      controlling HPV replication may allow development of novel anti-HPV therapeutics.
      Infectious HPV virions are produced during terminal differentiation of host
      cells. The process of viral maturation requires synergistic interactions between
      viral and cellular proteins that leads to amplification of the viral genome and
      expression of late viral genes. Here we show that the transcription factor
      Kruppel-like factor 13 (KLF13) has a critical role in the HPV life cycle. KLF13
      is overexpressed in HPV-positive keratinocytes and cervical cancer cell lines.
      Expression of KLF13 in normal cervical epithelium is low but increases
      significantly in cervical intraepithelial neoplasia and invasive squamous
      cervical cancer. After HPV infection, the E7 protein suppresses ubiquitin ligase
      FBW7 expression leading to an increase in KLF13 expression. Reduction of KLF13
      with short hairpin RNA in differentiating HPV-positive cells resulted in
      diminished levels of viral gene expression and genome amplification. Knockdown of
      KLF13 also reduced the level of the transcription factor signal transducer and
      activator of transcription 5, which led to the downregulation of the ataxia
      telangiectasia mutated DNA damage pathway and the chemokine interleukin-8 (IL-8).
      In addition, neutralization of IL-8 diminished viral genome amplification in
      differentiating HPV-positive cells. Thus, KLF13 is critical for the activation of
      the HPV productive life cycle and is likely involved in initiation and
      progression of cervical cancer.

PMID- 27041563
TI  - The hypusine cascade promotes cancer progression and metastasis through the
      regulation of RhoA in squamous cell carcinoma.
AB  - Metastasis is a critical factor contributing to poor prognosis in cancer, but the
      underlying mechanisms of metastasis are still poorly understood. We established a
      highly metastatic cell subline (HOC313-LM) derived from an oral squamous cell
      carcinoma cell line (HOC313) for uncovering the mechanisms of metastasis, and
      identified deoxyhypusine synthase (DHPS) as a metastasis-associated gene within
      the specific amplification at 19p13.2-p13.13 in HOC313-LM. DHPS-mediated hypusine
      modification of eukaryotic translation factor 5A facilitated the translation of
      RhoA, resulting in the activation of the RhoA signaling pathway and leading to
      not only increased cell motility, invasion and metastasis of cancer cells in
      vitro, but also increased tumor growth in vivo. Moreover, the use of N1-Guanyl
      1,7-diaminoheptane, a DHPS inhibitor, resulted in a significant decrease in tumor
      formation in vivo. In patients with esophageal squamous cell carcinoma (ESCC),
      overexpression of DHPS in ESCC tumors was significantly associated with worse
      recurrence-free survival, and correlated with distant metastasis. The elucidation
      of these molecular mechanisms within the hypusine cascade suggests opportunities
      for novel therapeutic targets in SCC.

PMID- 27041564
TI  - The PLA2R1-JAK2 pathway upregulates ERRalpha and its mitochondrial program to
      exert tumor-suppressive action.
AB  - Little is known about the biological role of the phospholipase A2 receptor
      (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an
      important role in regulating tumor-suppressive responses via JAK2 activation, but
      the underlying mechanisms are largely undeciphered. In this study, we observed
      that PLA2R1 increases the mitochondrial content, judged by increased levels of
      numerous mitochondrial proteins, of the mitochondrial structural component
      cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA
      replication and transcription factor TFAM. This effect of PLA2R1 relies on a
      transcriptional program controlled by the estrogen-related receptor alpha1
      (ERRalpha) mitochondrial master regulator. Expression of ERRalpha and of its
      nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic
      expression, and this effect is mediated by JAK2. Conversely, downregulation of
      PLA2R1 decreases the level of ERRalpha and of its nucleus-encoded mitochondrial
      targets. Finally, blocking the ERRalpha-controlled mitochondrial program largely
      inhibits the PLA2R1-induced tumor-suppressive response. Together, our data
      document ERRalpha and its mitochondrial program as downstream effectors of the
      PLA2R1-JAK2 pathway leading to oncosuppression.

PMID- 27041565
TI  - MDM2 oligomers: antagonizers of the guardian of the genome.
AB  - Over two decades of MDM2 research has resulted in the accumulation of a wealth of
      knowledge of many aspects of MDM2 regulation and function, particularly with
      respect to its most prominent target, p53. For example, recent knock-in mouse
      studies have shown that MDM2 heterooligomer formation with its homolog, MDMX, is
      necessary and sufficient in utero to suppress p53 but is dispensable during
      adulthood. However, despite crucial advances such as these, several aspects
      regarding basic in vivo functions of MDM2 remain unknown. In one such example,
      although abundant evidence suggests that MDM2 forms homooligomers and
      heterooligomers with MDMX, the function and regulation of these homo- and
      heterooligomers in vivo remain incompletely understood. In this review, we
      discuss the current state of our knowledge of MDM2 oligomerization as well as
      current efforts to target the MDM2 oligomer as a broad therapeutic option for
      cancer treatment.

PMID- 27041566
TI  - Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of
      osteosarcoma cell death.
AB  - Osteosarcoma (OS) is the most common cancer of bone and the 5th leading cause of
      cancer-related death in young adults. Currently, 5-year survival rates have
      plateaued at ~70% for patients with localized disease. Those with disseminated
      disease have an ~20% 5-year survival. An improved understanding of the molecular
      genetics of OS may yield new approaches to improve outcomes for OS patients. To
      this end, we applied murine models that replicate human OS to identify and
      understand dysregulated microRNAs (miRNAs) in OS. miRNA expression patterns were
      profiled in murine primary osteoblasts, osteoblast cultures and primary OS cell
      cultures (from primary and paired metastatic locations) isolated from two
      genetically engineered murine models of OS. The differentially expressed miRNA
      were further assessed by a cross-species comparison with human osteoblasts and OS
      cultures. We identified miR-155-5p and miR-148a-3p as deregulated in OS. miR-155
      5p suppression or miR-148a-3p overexpression potently reduced proliferation and
      induced apoptosis in OS cells, yet strikingly, did not impact normal osteoblasts.
      To define how these miRNAs regulated OS cell fate, we used an integrated
      computational approach to identify putative candidate targets and then correlated
      these with the cell biological impact. Although we could not resolve the
      mechanism through which miR-148a-3p impacts OS, we identified that miR-155-5p
      overexpression suppressed its target Ripk1 (receptor (TNFRSF)-interacting serine
      threonine kinase 1) expression, and miR-155-5p inhibition elevated Ripk1 levels.
      Ripk1 is directly involved in apoptosis/necroptosis. In OS cells, small
      interfering RNA against Ripk1 prevented cell death induced by the sequestration
      of miR-155-5p. Collectively, we show that miR-148a-3p and miR-155-5p are species
      conserved deregulated miRNA in OS. Modulation of these miRNAs was specifically
      toxic to tumor cells but not normal osteoblasts, raising the possibility that
      these may be tractable targets for miRNA-based therapies for OS.

PMID- 27041567
TI  - Regulation of Numb isoform expression by activated ERK signaling.
AB  - The endocytic adaptor protein Numb has a major role in development as an
      intrinsic regulator of cell fate determination and inhibitor of the Notch
      signaling pathway. In vertebrates, four protein isoforms of Numb are produced
      through alternative splicing (AS) of two cassette exons (exons 3 and 9). AS of
      coding exon 9 (E9) produces E9-included (p72/p71) and -excluded (p66/p65) protein
      products. Expression of Numb isoforms is developmentally regulated and E9
      included products are expressed in progenitors, whereas E9-excluded isoforms are
      dominantly expressed in differentiated cells. Analyses of AS events in multiple
      cancers previously identified a switch in Numb transcript and protein expression
      from the E9-excluded to the E9-included isoform, suggesting that misregulation of
      the mechanisms that control E9 inclusion may have a role in tumorigenesis. Here
      we identify splicing factors ASF/SF2 and PTBP1 as regulators of E9 splicing and
      show that activation of the mitogen-activated protein kinase/extracellular signal
      regulated kinase pathway promotes E9 inclusion in cancer cells. Our evidence
      supports a mechanism by which Numb AS is regulated in response to oncogenic
      signaling pathways, and contributes to activation of downstream pathways to
      promote tumorigenesis.

PMID- 27041568
TI  - Twinstar/cofilin is required for regulation of epithelial integrity and tissue
      growth in Drosophila.
AB  - Regulation of actin assembly and depolymerization is important for the
      organization of epithelia. Recent studies have shown that the actin-capping
      proteins are required to prevent cell extrusion and inappropriate activation of
      Yorkie (Yki) activity in Drosophila, implicating the importance of actin
      regulation for epithelial integrity and Yki-dependent tissue growth. However, the
      role of Twinstar (Tsr), the Drosophila homolog for cofilin/actin depolymerization
      factor (ADF), in epithelial integrity and Hippo signaling is unknown. Here we
      demonstrate that reduction of Tsr by RNA interference (RNAi) or mutant clones in
      wing imaginal disc induces not only F-actin accumulation but also ectopic
      expression of Wingless (Wg) and Yki target gene expanded (ex). Knockdown of Yki
      in Tsr-depleted cells reduced the level of ectopic Wg expression. Reduced Tsr
      also led to downregulation of cell junction proteins and extrusion of affected
      cells from the basal part of the epithelium. Rho GTPase 1 was upregulated in Tsr
      depleted tissue, supporting the Tsr function in the inhibition of cell extrusion
      from the epithelium. Tsr is also required for blocking cell death and c-Jun N
      terminal kinase (JNK) signaling. Ectopic JNK activation induced caspase
      activation but did not cause cell extrusion. Further, the invasiveness of Tsr
      depleted cells was not suppressed by inhibition of cell death or JNK signaling.
      In contrast, Yki upregulation was significantly suppressed by cell death
      inhibition. Taken together, our data suggest that Tsr is required for cell
      survival and tissue growth by regulating JNK and Yki signaling while maintaining
      the epithelial integrity by controlling cell junctions. This study provides an
      insight into potential roles of ADF/cofilin in invasive cell migration and tumor
      suppression in higher animals.

PMID- 27041569
TI  - AMPK promotes tolerance to Ras pathway inhibition by activating autophagy.
AB  - Targeted inhibitors of oncogenic Ras (rat sarcoma viral oncogene)-Raf signaling
      have shown great promise in the clinic, but resistance remains a major challenge:
      30% of tumors with pathway mutations do not respond to targeted inhibitors, and
      of the 70% that do respond, all eventually develop resistance. Before cancer
      cells acquire resistance, they respond to initial drug treatment either by
      undergoing apoptosis ('addiction') or by surviving treatment albeit with reduced
      growth ('tolerance'). As these drug-tolerant cells serve as a reservoir from
      which resistant cells eventually emerge, inhibiting the pathways that confer
      tolerance could potentially delay or even prevent recurrence. Here, we show that
      melanomas and other cancers acquire tolerance to Ras-Raf pathway inhibitors by
      activating autophagy, which is mediated by the cellular energy sensor AMP
      activated protein kinase (AMPK). Blocking this AMPK-mediated autophagy sensitizes
      drug-tolerant melanomas to Ras-Raf pathway inhibitors. Conversely, activating
      AMPK signaling and autophagy enables melanomas that would otherwise be addicted
      to the Ras-Raf pathway to instead tolerate pathway inhibition. These findings
      identify a key mechanism of tolerance to Ras-Raf pathway inhibitors and suggest
      that blocking either AMPK or autophagy in combination with these targeted
      inhibitors could increase tumor regression and decrease the likelihood of
      eventual recurrence.

PMID- 27041570
TI  - NF-kappaB-HOTAIR axis links DNA damage response, chemoresistance and cellular
      senescence in ovarian cancer.
AB  - The transcription factor nuclear factor kappa B (NF-kappaB) and the long non
      coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) have diverse functional
      roles in cancer. In this study, we show that upregulation of HOTAIR induced
      platinum resistance in ovarian cancer, and increased HOTAIR levels were observed
      in recurrent platinum-resistant ovarian tumors vs primary ovarian tumors. To
      investigate the role of HOTAIR during DNA damage induced by platinum, we
      monitored double-strand breaks and show that HOTAIR expression results in
      sustained activation of DNA damage response (DDR) after platinum treatment. We
      demonstrate that ectopic expression of HOTAIR induces NF-kappaB activation during
      DDR and interleukin-6 and interleukin-6 expression, both key NF-kappaB target
      genes. We show that HOTAIR regulates activation of NF-kappaB by decreasing Ikappa
      Balpha (NF-kappaB inhibitor) and establish that by inducing prolonged NF-kappaB
      activation and expression of NF-kappaB target genes during DNA damage, HOTAIR has
      a critical role in cellular senescence and platinum sensitivity. Our findings
      suggest that an NF-kappaB-HOTAIR axis drives a positive-feedback loop cascade
      during DDR and contributes to cellular senescence and chemotherapy resistance in
      ovarian and other cancers.

PMID- 27041571
TI  - SHP-2-upregulated ZEB1 is important for PDGFRalpha-driven glioma epithelial
      mesenchymal transition and invasion in mice and humans.
AB  - Gliomas are highly malignant brain tumors that are highly invasive and resistant
      to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRalpha
      (platelet-derived growth factor receptor-alpha), which show frequent aberrant
      activation in gliomas, are associated with a process of epithelial-mesenchymal
      transition (EMT), a cellular alteration that confers a more invasive and drug
      resistant phenotype. Although this phenomenon is well documented in human
      cancers, the processes by which RTKs including PDGFRalpha mediate EMT are largely
      unknown. Here, we report that SHP-2 (encoded by PTPN11) upregulates an EMT
      inducer, ZEB1, to mediate PDGFRalpha-driven glioma EMT, invasion and growth in
      glioma cell lines and patient-derived glioma stem cells (GSCs) using cell culture
      and orthotopic xenograft models. ZEB1 and activated PDGFRalpha were coexpressed
      in invasive regions of mouse glioma xenografts and clinical glioma specimens.
      Glioma patients with high levels of both phospho-PDGFRalpha (p-PDGFRalpha) and
      ZEB1 had significantly shorter overall survival compared with those with low
      expression of p-PDGFRalpha and ZEB1. Knockdown of ZEB1 inhibited PDGFA/PDGFRalpha
      stimulated glioma EMT, tumor growth and invasion in glioma cell lines and patient
      derived GSCs. PDGFRalpha mutant deficient of SHP2 binding (PDGFRalpha-F720) or
      phosphoinositide 3-kinase (PI3K) binding (PDGFRalpha-F731/42), knockdown of SHP2
      or treatments of pharmacological inhibitor for PDGFRalpha-signaling effectors
      attenuated PDGFA/PDGFRalpha-stimulated ZEB1 expression, cell migration and GSC
      proliferation. Importantly, SHP-2 acts together with PI3K/AKT to regulate a ZEB1
      miR-200 feedback loop in PDGFRalpha-driven gliomas. Taken together, our findings
      uncover a new pathway in which ZEB1 functions as a key regulator for PDGFRalpha
      driven glioma EMT, invasiveness and growth, suggesting that ZEB1 is a promising
      therapeutic target for treating gliomas with high PDGFRalpha activation.

PMID- 27041572
TI  - Interaction of hepatitis B virus X protein with PARP1 results in inhibition of
      DNA repair in hepatocellular carcinoma.
AB  - Hepatitis B virus X protein (HBx) contributes to the development of
      hepatocellular carcinoma (HCC), probably by regulating activities of many host or
      viral proteins through protein-protein interactions. In this study, we identified
      poly(ADP-ribose) polymerase (PARP1), a crucial factor in DNA repair, as an HBx
      interacting protein using a proteomics approach. Coimmunoprecipitation and
      proximity ligation assays confirmed the binding and colocalization of HBx and
      PARP1 in the nucleus. The carboxyl-terminus of HBx protein bound to the catalytic
      domain of PARP1, and this binding reduced the enzymatic activity of PARP1 in both
      in vitro and in vivo assays. HBx interrupted the binding of PARP1 to Sirt6, which
      catalyzes the mono-ADP-ribosylation required for DNA repair. Consistently,
      overexpression of HBx inhibited the clearance of gammaH2AX DNA repair foci
      generated under oxidative stress in Chang liver cells. Recruitment of the DNA
      repair complex to the site-specific double-strand breaks was inhibited in the
      presence of HBx, when measured by laser microirradiation assay and damage
      specific chromatin immunoprecipitation assays. Consequently, HBx increased signs
      of DNA damage such as accumulation of 8-hydroxy-2'-deoxyguanosine and comet
      formation, which were reversed by overexpression of PARP1 and/or Sirt6. Finally,
      the interaction between PARP1 and Sirt6 was markedly lower in the livers of HBx
      transgenic mice and specimens obtained from HCC patients to compare with the
      corresponding control. Our data suggest that the physical interaction of HBx and
      PARP1 accelerates DNA damage by inhibiting recruitment of the DNA repair complex
      to the damaged DNA sites, which may lead to the onset of hepatocarcinogenesis.

PMID- 27041573
TI  - Tumour-processed osteopontin and lactadherin drive the protumorigenic
      reprogramming of microglia and glioma progression.
AB  - Tumour tissue is infiltrated by myeloid cells that are reprogrammed into
      alternatively activated/regenerative (M2) macrophages. The contribution of major
      signalling pathways and their modulators/targets involved in the macrophage
      reprogramming is poorly known. Glioblastoma (malignant brain tumour) attracts and
      reprograms brain-resident microglia and peripheral macrophages into cells that
      increase invasion, angiogenesis and suppress antitumour immunity. Using a
      'function-first' approach and glioma secretome proteomics we identified
      osteopontin and lactadherin as proteins that cooperatively activate amoeboid
      transformation, phagocytosis and motility of primary microglia cultures via
      integrins and FAK-Akt (focal adhesion kinase-Akt) signalling. A synthetic peptide
      interfering with integrin ligands blocks glioma-microglia communication,
      functional activation and M2 gene expression. We found that osteopontin/secreted
      phosphoprotein 1 (Spp1) produced by non-transformed cells acts as a
      proinflammatory factor inducing inflammatory signalling and M1 genes, and
      counteracts the action of lactadherin. Using constructs encoding functional
      mutants of osteopontin, we demonstrated sequential processing of Spp1 by thrombin
      and matrix metalloproteinase-3 and/or -7 (MMP-3 and/or -7) in glioma cells, which
      generates a microglia-activating form devoid of the inflammatory activity, while
      retaining the M2 reprogramming potential. A similar form of osteopontin is
      secreted by human glioma cells but not normal human astrocytes. Knockdown of
      osteopontin or lactadherin in glioma cells reduces intracranial glioma growth,
      blocks amoeboid transformation of myeloid cells and affects M2 reprogramming of
      microglia/macrophages. Our findings demonstrate how glioma cells misuse
      macrophage-activating signals and redesign primarily proinflammatory signals
      towards their advantage to induce M2 reprogramming of tumour-infiltrating brain
      macrophages.

PMID- 27041574
TI  - PRR14 is a novel activator of the PI3K pathway promoting lung carcinogenesis.
AB  - Chromosomal focal amplifications often cause an increase in gene copy number,
      contributing to the pathogenesis of cancer. PRR14 overexpression is associated
      with recurrent locus amplification in lung cancer, and it correlates with a poor
      prognosis. We show that increased PRR14 expression promoted and reduced PRR14
      expression impeded lung cancer cell proliferation. Interestingly, PRR14 cells
      were markedly enlarged in size and exhibited an elevated activity of the PI3
      kinase/Akt/mTOR pathway, which was associated with a heightened sensitivity to
      the inhibitors of PI3K and mammalian target of rapamycin (mTOR). Biochemical
      analysis revealed that PRR14, as a proline-rich protein, binds to the Src
      homology 3 (SH3) domains of GRB2 resulting in PI3K activation. Significantly, two
      cancer patient-derived PRR14 mutants displayed considerably augmented GRB2
      binding and an enhanced ability of promoting cell proliferation. Together with
      the in vivo data demonstrating a strong tumor-promoting activity of PRR14 and the
      mutants, our work uncovered this proline-rich protein as a novel activator of the
      PI3K pathway that promoted tumorigenesis in lung cancer.

PMID- 27041575
TI  - An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in
      presentation chronic lymphocytic leukaemia cases using multiple polymerases.
AB  - Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder
      characterized by clonal diversity, a relapsing and remitting course, and in its
      aggressive forms remains largely incurable. Current front-line regimes include
      agents such as fludarabine, which act primarily via the DNA damage response
      pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene,
      altering p53 functionality, are associated with genetic instability, and are
      present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in
      relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate
      detection of sub-clonal TP53 mutations prior to and during treatment may be
      indicative of early relapse. In this study, we describe a novel deep sequencing
      workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq),
      facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%,
      in presentation CLL cases tested. As these mutations were mostly clustered within
      the regions of TP53 encoding DNA-binding domains, essential for DNA contact and
      structural architecture, they are likely to be of prognostic relevance in disease
      progression. The workflow described here has the potential to be implemented
      routinely to identify rare mutations across a range of diseases.

PMID- 27041576
TI  - Vitamin D/vitamin D receptor axis regulates DNA repair during oncogene-induced
      senescence.
AB  - Oncogenic Ras expression is associated with activation of the DNA damage response
      (DDR) pathway, as evidenced by elevated DNA damage, primarily DNA double-strand
      breaks (DSBs), and activation of DNA damage checkpoints, which in primary human
      cells leads to entry into senescence. DDR activation is viewed as a physiological
      barrier against uncontrolled proliferation in oncogenic Ras-expressing cells, and
      arises in response to genotoxic stress due to the production of reactive oxygen
      species that damage DNA and to hyper-replication stress. Although oncogene
      induced senescence (OIS) is considered a tumor suppressor mechanism, the
      accumulation of DNA damage in senescent cells is thought to cause genomic
      instability, eventually allowing secondary hits in the genome that promote
      tumorigenesis. To date, the molecular mechanisms behind DNA repair defects during
      OIS remain poorly understood. Here, we show that oncogenic Ras expression in
      human primary cells results in the downregulation of BRCA1 and 53BP1, two key
      factors in DNA DSB repair by homologous recombination and non-homologous end
      joining, respectively. As a consequence, Ras-induced senescent cells are hindered
      in their ability to recruit BRCA1 and 53BP1 to DNA damage sites. Whereas BRCA1 is
      downregulated at transcripts levels, 53BP1 loss is caused by activation of
      cathepsin L-mediated degradation of 53BP1 protein. Moreover, we discovered a
      marked downregulation of vitamin D receptor (VDR) during OIS, and a role for the
      vitamin D/VDR axis regulating the levels of these DNA repair factors during OIS.
      This study reveals a new functional relationship between the oncogene Ras, the
      vitamin D/VDR axis and the expression of DNA repair factors, in the context of
      OIS. The observed deficiencies in DNA repair factors in senescent cells could
      contribute to the genomic instability that allows senescence bypass and
      tumorigenesis.

PMID- 27041577
TI  - CD146 is a novel marker for highly tumorigenic cells and a potential therapeutic
      target in malignant rhabdoid tumor.
AB  - Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy
      that primarily develops during infancy and early childhood. Despite the existing
      standard of intensive multimodal therapy, the prognosis of patients with MRT is
      dismal; therefore, a greater understanding of the biology of this disease is
      required to establish novel therapies. In this study, we identified a highly
      tumorigenic sub-population in MRT, based on the expression of CD146 (also known
      as melanoma cell adhesion molecule), a cell adhesion molecule expressed by neural
      crest cells and various derivatives. CD146+ cells isolated from four MRT cell
      lines by cell sorting exhibited enhanced self-renewal and invasive potential in
      vitro. In a xenograft model using immunodeficient NOD/Shi-scid IL-2Rgamma-null
      mice, purified CD146+ cells obtained from MRT cell lines or a primary tumor
      exhibited the exclusive ability to form tumors in vivo. Blocking of CD146-related
      mechanisms, either by short hairpin RNA knockdown or treatment with a polyclonal
      antibody against CD146, effectively suppressed tumor growth of MRT cells both in
      vitro and in vivo via induction of apoptosis by inactivating Akt. Furthermore,
      CD146 positivity in immunohistological analysis of 11 MRT patient samples was
      associated with poor patient outcomes. These results suggest that CD146 defines a
      distinct sub-population in MRT with high tumorigenic capacity and that this
      marker represents a promising therapeutic target.

PMID- 27041578
TI  - Epigenetic silencing of miR-124 prevents spermine oxidase regulation:
      implications for Helicobacter pylori-induced gastric cancer.
AB  - Chronic inflammation contributes to the development of various forms of cancer.
      The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic
      inflammatory conditions, including Helicobacter pylori-associated gastritis,
      where its production of hydrogen peroxide contributes to DNA damage and
      subsequent tumorigenesis. MicroRNA expression levels are also altered in
      inflammatory conditions; specifically, the tumor suppressor miR-124 becomes
      silenced by DNA methylation. We sought to determine if this repression of miR-124
      is associated with elevated SMOX activity and concluded that miR-124 is indeed a
      negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly
      methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR
      124 re-expression and decreased SMOX expression. Overexpression of an exogenous
      miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2
      production by >50% within 24 h. Reporter assays indicated that direct interaction
      of miR-124 with the 3'-untranslated region of SMOX mRNA contributes to this
      negative regulation. Importantly, overexpression of miR-124 before infection with
      H. pylori prevented the induction of SMOX believed to contribute to inflammation
      associated tumorigenesis. Compelling human in vivo data from H. pylori-positive
      gastritis tissues indicated that the mir-124 gene loci are more heavily
      methylated in a Colombian population characterized by elevated SMOX expression
      and a high risk for gastric cancer. Furthermore, the degree of mir-124
      methylation significantly correlated with SMOX expression throughout the
      population. These results indicate a protective role for miR-124 through the
      inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated
      gastric cancer.

PMID- 27041579
TI  - FOXC1 is involved in ERalpha silencing by counteracting GATA3 binding and is
      implicated in endocrine resistance.
AB  - Estrogen receptor-alpha (ERalpha) mediates the essential biological function of
      estrogen in breast development and tumorigenesis. Multiple mechanisms, including
      pioneer factors, coregulators and epigenetic modifications have been identified
      as regulators of ERalpha signaling in breast cancer. However, previous studies of
      ERalpha regulation have focused on luminal and HER2-positive subtypes rather than
      basal-like breast cancer (BLBC), in which ERalpha is underexpressed. In addition,
      mechanisms that account for the decrease or loss of ER expression in recurrent
      tumors after endocrine therapy remain elusive. Here, we demonstrate a novel FOXC1
      driven mechanism that suppresses ERalpha expression in breast cancer. We find
      that FOXC1 competes with GATA-binding protein 3 (GATA3) for the same binding
      regions in the cis-regulatory elements upstream of the ERalpha gene and thereby
      downregulates ERalpha expression and consequently its transcriptional activity.
      The forkhead domain of FOXC1 is essential for the competition with GATA3 for DNA
      binding. Counteracting the action of GATA3 at the ERalpha promoter region,
      overexpression of FOXC1 hinders recruitment of RNA polymerase II and increases
      histone H3K9 trimethylation at ERalpha promoters. Importantly, ectopic FOXC1
      expression in luminal breast cancer cells reduces sensitivity to estrogen and
      tamoxifen. Furthermore, in breast cancer patients with ER-positive primary tumors
      who received adjuvant tamoxifen treatment, FOXC1 expression is associated with
      decreased or undetectable ER expression in recurrent tumors. Our findings
      highlight a clinically relevant mechanism that contributes to the low or absent
      ERalpha expression in BLBC. This study suggests a new paradigm to study ERalpha
      regulation during breast cancer progression and indicates a role of FOXC1 in the
      modulation of cellular response to endocrine treatment.

PMID- 27041580
TI  - A comprehensive profile of recurrent glioblastoma.
AB  - In spite of relentless efforts to devise new treatment strategies, primary
      glioblastomas invariably recur as aggressive, therapy-resistant relapses and
      patients rapidly succumb to these tumors. Many therapeutic agents are first
      tested in clinical trials involving recurrent glioblastomas. Remarkably, however,
      fundamental knowledge on the biology of recurrent glioblastoma is just slowly
      emerging. Here, we review current knowledge on recurrent glioblastoma and ask
      whether and how therapies change intra-tumor heterogeneity, molecular traits and
      growth pattern of glioblastoma, and to which extent this information can be
      exploited for therapeutic decision-making. We conclude that the ability to
      characterize and predict therapy-induced changes in recurrent glioblastoma will
      determine, whether, one day, glioblastoma can be contained in a state of chronic
      disease.

PMID- 27041581
TI  - Regulation of a TGF-beta1-CD147 self-sustaining network in the differentiation
      plasticity of hepatocellular carcinoma cells.
AB  - Cellular plasticity has an important role in the progression of hepatocellular
      carcinoma (HCC). In this study, the involvement of a TGF-beta1-CD147 self
      sustaining network in the regulation of the dedifferentiation progress was fully
      explored in HCC cell lines, hepatocyte-specific basigin/CD147-knockout mice and
      human HCC tissues. We demonstrated that TGF-beta1 stimulation upregulated CD147
      expression and mediated the dedifferentiation of HCC cells, whereas all-trans
      retinoic acid induced the downregulation of CD147 and promoted differentiation in
      HCC cells. Overexpression of CD147 induced the dedifferentiation and enhanced the
      malignancy of HCC cells, and increased the transcriptional expression of TGF
      beta1 by activating beta-catenin. CD147-induced matrix metalloproteinase (MMP)
      production activated pro-TGF-beta1. The activated TGF-beta1 signaling
      subsequently repressed the HNF4alpha expression via Smad-Snail1 signaling and
      enhanced the dedifferentiation progress. Hepatocyte-specific basigin/CD147
      knockout mice decreased the susceptibility to N-nitrosodiethylamine-induced
      tumorigenesis by suppressing TGF-beta1-CD147 signaling and inhibiting
      dedifferentiation in hepatocytes during tumor progression. CD147 was positively
      correlated with TGF-beta1 and negatively correlated with HNF4alpha in human HCC
      tissues. Positive CD147 staining and lower HNF4alpha levels in tumor tissues were
      significantly associated with poor survival of patients with HCC. The
      overexpression of HNF4alpha and Smad7 and the deletion of CD147 by lentiviral
      vectors jointly reprogrammed the expression profile of hepatocyte markers and
      attenuated malignant properties including proliferation, cell survival and tumor
      growth of HCC cells. Our results highlight the important role of the TGF-beta1
      CD147 self-sustaining network in driving HCC development by regulating
      differentiation plasticity, which provides a strong basis for further
      investigations of the differentiation therapy of HCC targeting TGF-beta1 and
      CD147.

PMID- 27041582
TI  - Osteocytic connexin hemichannels suppress breast cancer growth and bone
      metastasis.
AB  - Although the skeleton is one of the predominant sites for breast cancer
      metastasis, why breast cancer cells often become dormant after homing to bone is
      not well understood. Here, we reported an intrinsic self-defense mechanism of
      bone cells against breast cancer cells: a critical role of connexin (Cx) 43
      hemichannels in osteocytes in the suppression of breast cancer bone metastasis.
      Cx43 hemichannels allow passage of small molecules between the intracellular and
      extracellular environments. The treatment of bisphosphonate drugs, either
      alendronate (ALN) or zoledronic acid (ZOL), opened Cx43 hemichannels in
      osteocytes. Conditioned media (CM) collected from MLO-Y4 osteocyte cells treated
      with bisphosphonates inhibited the anchorage-independent growth, migration and
      invasion of MDA-MB-231 human breast cancer cells and Py8119 mouse mammary
      carcinoma cells, and this inhibitory effect was attenuated with Cx43(E2), a
      specific hemichannel-blocking antibody. The opening of osteocytic Cx43
      hemichannels by mechanical stimulation had similar inhibitory effects on breast
      cancer cells and this inhibition was attenuated by Cx43(E2) antibody as well.
      These inhibitory effects on cancer cells were mediated by ATP released from
      osteocyte Cx43 hemichannels. Furthermore, both Cx43 osteocyte-specific knockout
      mice and osteocyte-specific Delta130-136 transgenic mice with impaired Cx43 gap
      junctions and hemichannels showed significantly increased tumor growth and
      attenuated the inhibitory effect of ZOL. However, R76W transgenic mice with
      functional hemichannels but not gap junctions in osteocytes did not display a
      significant difference. Together, our studies establish the specific inhibitory
      role of osteocytic Cx43 hemichannels, and exploiting the activity of this channel
      could serve as a de novo therapeutic strategy.

PMID- 27041583
TI  - The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator
      and a prognostic marker in breast cancer.
AB  - Heparan sulfate (HS) proteoglycan chains are key components of the breast tumor
      microenvironment that critically influence the behavior of cancer cells. It is
      established that abnormal synthesis and processing of HS play a prominent role in
      tumorigenesis, albeit mechanisms remain mostly obscure. HS function is mainly
      controlled by sulfotransferases, and here we report a novel cellular and
      pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A),
      catalyzing the final maturation step of HS, in breast cancer. We show that 3
      OST3A is epigenetically repressed in all breast cancer cell lines of a panel
      representative of distinct molecular subgroups, except in human epidermal growth
      factor receptor 2-positive (HER2+) sloan-kettering breast cancer (SKBR3) cells.
      Epigenetic mechanisms involved both DNA methylation and histone modifications,
      producing different repressive chromatin environments depending on the cell
      molecular signature. Gain and loss of function experiments by cDNA and siRNA
      transfection revealed profound effects of 3-OST3A expression on cell behavior
      including apoptosis, proliferation, response to trastuzumab in vitro and tumor
      growth in xenografted mice. 3-OST3A exerted dual activities acting as tumor
      suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD
      Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in
      HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer
      fluorescence-lifetime imaging microscopy experiments indicated that the effects
      of 3-OST3A in MCF-7 cells were mediated by altered interactions between HS and
      fibroblast growth factor-7 (FGF-7). Further, this interplay between HS and FGF-7
      modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3-O
      sulfation affects FGFR2IIIb-mediated signaling. Corroborating our cellular data,
      a clinical study conducted in a cohort of breast cancer patients uncovered that,
      in HER2+ patients, high level expression of 3-OST3A in tumors was associated with
      reduced relapse-free survival. Our findings define 3-OST3A as a novel regulator
      of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic
      activities in a cell- and tumor-dependent context, and demonstrate the clinical
      value of the HS-O-sulfotransferase 3-OST3A as a prognostic marker in HER2+
      patients.

PMID- 27041584
TI  - CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by
      mediating U2AF2 ubiquitination and degradation.
AB  - Melanoma is one of the most lethal forms of skin cancer because of its early
      metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein,
      is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44
      alternative splicing in melanoma and its pathogenic contributions are so far
      poorly understood. Here, we investigated the expression level of CD44 in a large
      set of melanocytic lesions at different stages. We found that the expression of
      CD44v8-10 and a splicing factor, U2AF2, is significantly increased during
      melanoma progression, whereas CD82/KAI1, a tetraspanin family of tumor
      suppressor, is reduced in metastatic melanoma. CD44v8-10 and U2AF2 expression
      levels, which are negatively correlated with CD82 levels, are markedly elevated
      in primary melanoma compared with dysplastic nevi and further increased in
      metastatic melanoma. We also showed that patients with higher CD44v8-10 and U2AF2
      expression levels tended to have shorter survival. By using both in vivo and in
      vitro assays, we demonstrated that CD82 inhibits the production of CD44v8-10 on
      melanoma. Mechanistically, U2AF2 is a downstream target of CD82 and in malignant
      melanoma facilitates CD44v8-10 alternative splicing. U2AF2-mediated CD44 isoform
      switch is required for melanoma migration in vitro and lung and liver metastasis
      in vivo. Notably, overexpression of CD82 suppresses U2AF2 activity by inducing
      U2AF2 ubiquitination. In addition, our data suggested that enhancement of
      melanoma migration by U2AF2-dependent CD44v8-10 splicing is mediated by Src/focal
      adhesion kinase/RhoA activation and formation of stress fibers, as well as CD44-E
      selectin binding reinforcement. These findings uncovered a hitherto unappreciated
      function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative
      splicing and cancer aggressiveness, with potential prognostic and therapeutic
      implications in melanoma.

PMID- 27041585
TI  - Rab1 in cell signaling, cancer and other diseases.
AB  - The endoplasmic reticulum (ER) and Golgi membrane system have major roles in cell
      signaling and regulation of the biosynthesis/transport of proteins and lipids in
      response to environmental cues such as amino acid and cholesterol levels. Rab1 is
      the founding member of the Rab small GTPase family, which is known to mediate
      dynamic membrane trafficking between ER and Golgi. Growing evidence indicate that
      Rab1 proteins have important functions beyond their classical vesicular transport
      functions, including nutrient sensing and signaling, cell migration and
      presentation of cell-surface receptors. Moreover, deregulation of RAB1 expression
      has been linked to a myriad of human diseases such as cancer, cardiomyopathy and
      Parkinson's disease. Further investigating these new physiological and
      pathological functions of Rab1 should provide new opportunities for better
      understanding of the disease processes and may lead to more effective therapeutic
      interventions.

PMID- 27041587
TI  - Intradural anterior transpetrosal approach.
AB  - The standard anterior transpetrosal approach (ATPA) for petroclival lesions is
      fundamentally an epidural approach and has been practiced for many decades quite
      successfully. However, this approach has some disadvantages, such as epidural
      venous bleeding around foramen ovale. We describe here our experience with a
      modified technique for anterior petrosectomy via an intradural approach that
      overcomes these disadvantages. Five patients with petroclival lesions underwent
      surgery via the intradural ATPA. The intraoperative hallmarks are detailed, and
      surgical results are reported. Total removal of the lesions was achieved in two
      patients with petroclival meningioma and two patients with pontine cavernoma,
      whereas subtotal removal was achieved in one patient with petroclival meningioma
      without significant morbidity. No patient experienced cerebrospinal fluid
      leakage. The intradural approach is allowed to tailor the extent of anterior
      petrosectomy to the individually required exposure, and the surgical procedure
      appeared to be more straightforward than via the epidural route. Caveats
      encountered with the approach were the temporal basal veins that could be spared
      as well as identification of the petrous apex due to the lack of familial
      epidural landmarks. The risk of injury to the temporal bridging veins is higher
      in this approach than in the epidural approach. Intradural approach is
      recommended in patients with a large epidural venous route, such as sphenobasal
      and sphenopetrosal vein. Navigation via bone-window computed tomography is useful
      to identify the petrous apex. 

PMID- 27041586
TI  - The role of barrier genes in epidermal malignancy.
AB  - The outermost layer of the mammalian skin, the epidermis, forms a protective
      barrier against pathogenic microbes and tissue dehydration. This barrier is
      formed and maintained by complex genetic networks that connect cellular
      differentiation processes, enzymatic activities and cellular junctions.
      Disruption in these networks affects the balance between keratinocyte
      proliferation and differentiation resulting in barrier function impairment,
      epidermal hyperproliferation and in some cases, squamous cell carcinoma (SCC).
      Recent studies in wound-induced inflammation-mediated cancers in mice have
      identified dysregulation of core barrier components as tumor drivers. We
      therefore propose a hypothesis in which loss of key barrier genes, induce barrier
      dysfunction, and promote inflammation-driven epidermal hyperplasia and
      carcinogenesis over time. This emerging vision suggests that under specific
      genetic circumstances, localized barrier impairment could be considered as a
      hallmark of initiating lesions in epidermal SCC.

PMID- 27041588
TI  - Increased expression of tissue inhibitor of metalloproteinase-1 correlates with
      improved outcome in canine cutaneous mast cell tumours.
AB  - Canine mast cell tumour (MCT) is a biologically heterogeneous disease. The
      extracellular matrix degradation promoted by matrix metalloproteinases (MMPs) has
      been studied in an attempt to elucidate the mechanisms involved in the biological
      behaviour of tumours. The aim of this study was to characterize the expression of
      MMP-2 and -9 and tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in canine
      cutaneous MCTs and to evaluate their prognostic values. Immunohistochemical
      staining for MMP-2, MMP-9, TIMP-2 and TIMP-1 was performed in 46 canine cases of
      MCTs. TIMP-1 expression showed an independent prognostic value for post-surgical
      survival and disease-related mortality. Dogs with MCTs showing less than 22.9%
      mast cell TIMP-1 positivity were more prone to die because of the disease and had
      a shorter post-surgical survival. This article suggests the involvement of TIMP-1
      in MCT progression, by contributing to a good outcome in patients with MCTs.

PMID- 27041589
TI  - Human Ischemic Cardiomyopathy Shows Cardiac Nos1 Translocation and its Increased
      Levels are Related to Left Ventricular Performance.
AB  - The role of nitric oxide synthase 1 (NOS1) as a major modulator of cardiac
      function has been extensively studied in experimental models; however, its role
      in human ischemic cardiomyopathy (ICM) has never been analysed. Thus, the
      objectives of this work are to study NOS1 and NOS-related counterparts involved
      in regulating physiological function of myocyte, to analyze NOS1 localisation,
      activity, dimerisation, and its relationship with systolic function in ICM. The
      study has been carried out on left ventricular tissue obtained from explanted
      human hearts. Here we demonstrate that the upregulation of cardiac NOS1 is not
      accompanied by an increase in NOS activity, due in part to the alterations found
      in molecules involved in the regulation of its activity. We observed partial
      translocation of NOS1 to the sarcolemma in ischemic hearts, and a direct
      relationship between its protein levels and systolic ventricular function. Our
      findings indicate that NOS1 may be significant in the pathophysiology of human
      ischemic heart disease with a preservative role in maintaining myocardial
      homeostasis. 

PMID- 27041591
TI  - Bisphenol A and food safety: Lessons from developed to developing countries.
AB  - Modern lifestyles and changes in the socio-economic characteristics of households
      have stimulated current developments in food technology, processing and
      packaging. Chemicals such as bisphenol A (BPA) are known to migrate from food
      packaging into the food, resulting in human exposure to these chemicals.
      Similarly, BPA can migrate from baby feeding bottles into milk. BPA has been
      associated with adverse effects attributed to its estrogenic properties in
      various animal models. This review analyzed peer-reviewed publications in the
      English literature on human BPA exposure and regulations in developing countries
      compared to developed countries. BPA has been reduced or eliminated from food
      packaging and contact materials such as baby bottles in developed countries
      either voluntarily or by legislation. The meager data from developing countries
      shows that human BPA exposure in developing countries is similar to that in
      developed countries. With minor exceptions, BPA restriction, voluntary or legal,
      is virtually absent in developing countries of Africa, SE Asia, and South and
      Central America. 

PMID- 27041592
TI  - Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.
AB  - The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples
      the ATPase cycle into motion to drive substrate translocation and degradation. A
      hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity
      by substrates. Here we report the structure of LonA bound to three ADPs,
      revealing the first AAA+ protease assembly where the six protomers are arranged
      alternately in nucleotide-free and bound states. Nucleotide binding induces large
      coordinated movements of conserved pore loops from two pairs of three non
      adjacent protomers and shuttling of the proteolytic groove between the ATPase
      site and a previously unknown Arg paddle. Structural and biochemical evidence
      supports the roles of the substrate-bound proteolytic groove in allosteric
      stimulation of ATPase activity and the conserved Arg paddle in driving substrate
      degradation. Altogether, this work provides a molecular framework for
      understanding how ATP-dependent chemomechanical movements drive allosteric
      processes for substrate degradation in a major protein-destruction machine.

PMID- 27041593
TI  - Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the
      Lon AAA+ Protease.
AB  - The Lon AAA+ protease (LonA) plays important roles in protein homeostasis and
      regulation of diverse biological processes. LonA behaves as a homomeric hexamer
      in the presence of magnesium (Mg(2+)) and performs ATP-dependent proteolysis.
      However, it is also found that LonA can carry out Mg(2+)-dependent degradation of
      unfolded protein substrate in an ATP-independent manner. Here we show that in the
      presence of Mg(2+) LonA forms a non-secluded hexameric barrel with prominent
      openings, which explains why Mg(2+)-activated LonA can operate as a diffusion
      based chambered protease to degrade unstructured protein and peptide substrates
      efficiently in the absence of ATP. A 1.85 A crystal structure of Mg(2+)-activated
      protease domain reveals Mg(2+)-dependent remodeling of a substrate-binding loop
      and a potential metal-binding site near the Ser-Lys catalytic dyad, supported by
      biophysical binding assays and molecular dynamics simulations. Together, these
      findings reveal the specific roles of Mg(2+) in the molecular assembly and
      activation of LonA.

PMID- 27041594
TI  - Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of
      HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region.
AB  - Evidence supports a role of antibody-dependent cellular cytotoxicity (ADCC)
      toward transitional epitopes in the first and second constant (C1-C2) regions of
      gp120 (A32-like epitopes) in preventing HIV-1 infection and in vaccine-induced
      protection. Here, we describe the first successful attempt at isolating the inner
      domain (ID) of gp120 as an independent molecule that encapsulates the A32-like
      region within a minimal structural unit of the HIV-1 Env. Through structure-based
      design, we developed ID2, which consists of the ID expressed independently of the
      outer domain and stabilized in the CD4-bound conformation by an inter-layer
      disulfide bond. ID2 expresses C1-C2 epitopes in the context of CD4-triggered full
      length gp120 but without any known neutralizing epitope present. Thus, ID2
      represents a novel probe for the analysis and/or selective induction of antibody
      responses to the A32 epitope region. We also present the crystal structure of ID2
      complexed with mAb A32, which defines its epitope.

PMID- 27041595
TI  - Manipulation of Subunit Stoichiometry in Heteromeric Membrane Proteins.
AB  - The ability of oligomeric membrane proteins to assemble in different functional
      ratios of subunits is a common feature across many systems. Recombinant
      expression of hetero-oligomeric proteins with defined stoichiometries facilitates
      detailed structural and functional analyses, but remains a major challenge. Here
      we present two methods for overcoming this challenge: one for rapid virus
      titration and another for stoichiometry determination. When these methods are
      coupled, they allow for efficient dissection of the heteromer stoichiometry
      problem and optimization of homogeneous protein expression. We demonstrate the
      utility of the methods in a system that to date has proved resistant to atomic
      scale structural study, the nicotinic acetylcholine receptor. Leveraging these
      two methods, we have successfully expressed, purified, and grown diffraction
      quality crystals of this challenging target.

PMID- 27041597
TI  - Editorial Comment.

PMID- 27041596
TI  - Structural Basis for Substrate Selectivity of the E3 Ligase COP1.
AB  - COP1 proteins are E3 ubiquitin ligases that regulate phototropism in plants and
      target transcription factors for degradation in mammals. The substrate-binding
      region of COP1 resides within a WD40-repeat domain that also binds to Trib
      proteins, which are adaptors for C/EBPalpha degradation. Here we report
      structures of the human COP1 WD40 domain in isolation, and complexes of the human
      and Arabidopsis thaliana COP1 WD40 domains with the binding motif of Trib1. The
      human and Arabidopsis WD40 domains are seven-bladed beta propellers with an
      inserted loop on the bottom face of the first blade. The Trib1 peptide binds in
      an extended conformation to a highly conserved surface on the top face of the
      beta propeller, indicating a general mode for recognition of peptide motifs by
      COP1. Together, these studies identify the structural basis and key interactions
      for motif recognition by COP1, and hint at how Trib1 autoinhibition is overcome
      to target C/EBPalpha for degradation.

PMID- 27041598
TI  - Multiple roles of putrescine and spermidine in stress resistance and virulence of
      Salmonella enterica serovar Typhimurium.
AB  - Polyamines (putrescine and spermidine) are small-cationic amines ubiquitous in
      nature and present in most living cells. In recent years they have been linked to
      virulence of several human pathogens including Shigella spp and Salmonella
      enterica serovar Typhimurium (S. Typhimurium). Central to S. Typhimurium
      virulence is the ability to survive and replicate inside macrophages and
      resisting the antimicrobial attacks in the form of oxidative and nitrosative
      stress elicited from these cells. In the present study, we have investigated the
      role of polyamines in intracellular survival and systemic infections of mice.
      Using a S. Typhimurium mutant defective for putrescine and spermidine
      biosynthesis, we show that polyamines are essential for coping with reactive
      nitrogen species, possibly linking polyamines to increased intracellular stress
      resistance. However, using a mouse model defective for nitric oxide production,
      we find that polyamines are required for systemic infections independently of
      host-produced reactive nitrogen species. To distinguish between the physiological
      roles of putrescine and spermidine, we constructed a strain deficient for
      spermidine biosynthesis and uptake, but with retained ability to produce and
      import putrescine. Interestingly, in this mutant we observe a strong attenuation
      of virulence during infection of mice proficient and deficient for nitric oxide
      production suggesting that spermidine, specifically, is essential for virulence
      of S. Typhimurium. 

PMID- 27041599
TI  - High-value care in the surgical intensive care unit: effect on ancillary
      resources.
AB  - BACKGROUND: Changes in health care policies have influenced transformations in
      hospital systems to be cost-efficient while maintaining robust outcomes. This is
      particularly important in intensive care units where significant resources are
      used to care for critically ill patients. We sought to determine whether high
      value care processes (HVCp) implemented in a surgical intensive care unit (SICU)
      have an impact on commonly used ancillary tests. MATERIALS AND METHODS: An
      implementation phase using a Lean Six Sigma approach was performed in October
      2014 at a 24-bed large academic center SICU with aims to decrease orders of
      excessive daily laboratory tests and X-rays. The HVCp implemented included use of
      daily checklists, staff education, and visual reminders emphasizing the
      importance of appropriate laboratory tests and chest X-rays. Preintervention
      (July 2014-October 2014) and post-intervention (November 2014-June 2015) phases
      were compared. RESULTS: Average SICU census, case mix index (4.3 versus 4.4, P =
      0.57), all patient refined severity of illness (3.2 versus 3.2, P = 0.91), and
      SICU mortality (7.1% versus 5.1%, P = 0.18) were similar in both phases. A
      significant reduction of excessive laboratory tests was evident after the
      implementation period. Eight hundred sixty-five arterial blood gases/mo were
      obtained in the preintervention phase compared with 420 arterial blood gases/mo
      after intervention (P = 0.004), representing a 51.4% reduction. Similar results
      were obtained with complete blood counts, basic metabolic profiles, coagulation
      profiles, and chest X-rays (12%, 17.8%, 30.2%, and 20.3% reductions,
      respectively), a total estimated cost savings of $59,137/mo and prevention of
      excess phlebotomy of approximately 4 L of blood/mo. CONCLUSIONS: By implementing
      an HVCp including a checklist, visual reminders, and provider education, we
      significantly reduced the use of commonly ordered ancillary tests in the SICU
      without affecting outcomes, resulting in an annual cost savings of $710,000.

PMID- 27041600
TI  - Weight loss after bariatric surgery: a propensity score analysis.
AB  - BACKGROUND: Laparoscopic vertical sleeve gastrectomy (LSG) has replaced
      laparoscopic Roux-en-Y gastric bypass (LRYGB) as the most commonly performed
      bariatric surgical procedure in the US for more than the past several years.
      Identifying which patients will achieve optimal outcomes remains challenging. We
      compared 90-d and 1-y outcomes between LSG and LRYGB patients and identified
      predictors of surgery type and excess body weight loss (EBWL). METHODS: Patient
      demographics, comorbidities, and weight loss were extracted from electronic
      health records of patients who underwent LRYGB (n = 270) or LSG (n = 74) from
      January 2010 through March 2014 at a single institution. Variables hypothesized
      to be associated with surgery type were included in a multivariable model to
      generate a propensity score for each patient. Propensity score-adjusted
      multivariable odds ratios (ORs) for characteristics associated with EBWL >50%
      were calculated. RESULTS: Overall 90-d complication rates were similar between
      the LRYGB and LSG cohorts. LRYGB patients had more frequent emergency department
      visits (27.1% versus 14.1%; P = 0.029) but similar rates of readmission (12.3%
      versus 8.5%; P = 0.53). Female sex, presence of gastroesophageal reflux disease,
      and surgeon age >=40 were associated with a greater likelihood of undergoing
      LRYGB. On propensity score-adjusted multivariable analysis, lower body mass index
      (OR 3.00 [95% confidence interval (CI) 1.66-5.40]), absence of type 2 diabetes
      (OR 2.55 [95% CI 1.43-4.54]), and undergoing LRYGB (OR 5.29 [95% CI 2.52-11.09])
      were associated with EBWL >50%. CONCLUSIONS: Sleeve gastrectomy patients had
      similar rates of complications compared with gastric bypass patients. Lower body
      mass index and absence of type 2 diabetes were associated with optimal weight
      loss. Incorporating these findings into preoperative discussions may help
      patients set reasonable postoperative goals.

PMID- 27041601
TI  - AN ECOLOGICAL REVIEW OF CLADOPHORA GLOMERATA (CHLOROPHYTA) IN THE LAURENTIAN
      GREAT LAKES(1).
AB  - Cladophora glomerata (L.) Kutz. is, potentially, the most widely distributed
      macroalga throughout the world's freshwater ecosystems. C. glomerata has been
      described throughout North America, Europe, the Atlantic Islands, the Caribbean
      Islands, Asia, Africa, Australia and New Zealand, and the Pacific Islands.
      Cladophora blooms were a common feature of the lower North American Great Lakes
      (Erie, Michigan, Ontario) from the 1950s through the early 1980s and were largely
      eradicated through the implementation of a multibillion-dollar phosphorus (P)
      abatement program. The return of widespread blooms in these lakes since the mid
      1990s, however, was not associated with increases in P loading. Instead, current
      evidence indicates that the resurgence in blooms was directly related to
      ecosystem level changes in substratum availability, water clarity, and P
      recycling associated with the establishment of dense colonies of invasive
      dreissenid mussels. These results support the hypothesis that dreissenid mussel
      invasions may induce dramatic shifts in energy and nutrient flow from pelagic
      zones to the benthic zone. 

PMID- 27041602
TI  - MORPHOLOGICAL AND GENETIC VARIATION IN THE POPULATIONS OF SARGASSUM HEMIPHYLLUM
      (PHAEOPHYCEAE) IN THE NORTHWESTERN PACIFIC(1).
AB  - Difficulty in species identification of Sargassum (Sargassaceae, Fucales) is
      partly attributed to the high polymorphism among its individuals and populations.
      This study aimed at assessing morphological and genetic variations in two
      varieties, var. hemiphyllum J. Agardh and var. chinense J. Agardh, of Sargassum
      hemiphyllum (Turner) C. Agardh, a widely distributed species in the northwestern
      Pacific. We investigated 26 measurable, five numerical, and 33 categorical
      morphological parameters associated with different branching levels of specimens
      from each of six localities within its distribution range using cluster analysis
      (CA) and principal coordinate analysis (PCoA). Leaf size of the primary and
      secondary branching levels and the vesicle size of the secondary branches of the
      specimens examined were determined to be the most important morphological
      parameters that were significantly different among populations. Change in leaf
      and vesicle length of individuals among the six populations followed a
      latitudinal gradient, with smaller leaves and vesicles associated with northern
      populations and larger ones in the southern populations. The possible influence
      of the gradual change in sea surface temperatures (SSTs) along this gradient in
      the northwestern Pacific on leaf and vesicle morphologies of this species was
      suggested. PCR-RFLP analysis of the RUBISCO spacer in the chloroplast genome
      revealed two distinct and highly homogenous clades, a China clade and a Japan
      Korea clade, which corresponded to var. chinense and var. hemiphyllum,
      respectively. The formation of refugia along the "Paleo-coast" in the East China
      Sea during glacial periods is suggested to have led to the vicariance of
      ancestral populations of S. hemiphyllum and thus to have promoted genetic
      differentiation. The massive freshwater outflow of the Yellow and Yangtze rivers
      may continue to act as a barrier, prolonging the allopatric distribution of the
      two varieties. 

PMID- 27041603
TI  - CONTROL OF REPRODUCTION RHYTHMICITY BY ENVIRONMENTAL AND ENDOGENOUS SIGNALS IN
      ULVA PSEUDOCURVATA (CHLOROPHYTA)(1).
AB  - A field population of Ulva pseudocurvata Koeman et C. Hoek (hereafter termed
      Ulva) at Sylt Island (North Sea, Germany) exhibited biweekly peaks of
      gametophytic reproduction during the colder seasons and approximately weekly
      peaks during summer. The reproductive events lasted 1-5 d and were separated from
      each other by purely vegetative phases. Under constant conditions in the
      laboratory, a free-running rhythm was observed with reproductive peaks occurring
      approximately every 7 d. When artificial moonlight was provided every 4 weeks,
      fewer reproductive events occurred, and the reproductive rhythm became
      synchronized to the environmental artificial moonlight rhythm. In the laboratory,
      apical disks were entirely converted into reproductive tissue after 8 d
      cultivation, while almost all basal disks stayed vegetative, which prevented the
      entire loss of the vegetative thallus during reproductive events. Seasonal size
      reduction of the thallus occurred from late autumn onward and was determined to
      be controlled by a genuine photoperiodic response, since size reduction could be
      induced from May onward by experimental short-day (SD) treatment but was
      prevented in a long-day (LD) or night-break regime (NB). A daily fine-tuning
      occurred with gamete release early in the morning at the first sign of daylight,
      following an obligatory dark ("night") period of at least 1 h duration. No
      release took place if the overnight dark phase was replaced by continuous light.
      Blue, green, or red light all triggered gamete release after a dark phase at an
      irradiance of 0.1 MUmol photons . m(-2)  .s(-1) , while 0.001 MUmol photons . m(
      2)  . s(-1) was equivalent to a dark control. 

PMID- 27041604
TI  - EFFECTS OF NUTRIENT ENRICHMENT ON PRIMARY PRODUCTION AND BIOMASS OF SEDIMENT
      MICROALGAE IN A SUBTROPICAL SEAGRASS BED(1).
AB  - Eutrophication of coastal waters often leads to excessive growth of microalgal
      epiphytes attached to seagrass leaves; however, the effect of increased nutrient
      levels on sediment microalgae has not been studied within seagrass communities. A
      slow-release NPK Osmocote fertilizer was added to sediments within and outside
      beds of the shoal grass Halodule wrightii, in Big Lagoon, Perdido Key, Florida.
      Gross primary production (GPP) and biomass (HPLC photopigments) of sediment
      microalgae within and adjacent to fertilized and control H. wrightii beds were
      measured following two 4-week enrichment periods during June and July 2004. There
      was no effect of position on sediment microalgal GPP or biomass in control and
      enriched plots. However, nutrient enrichment significantly increased GPP in both
      June and July. These results suggest that sediment microalgae could fill some of
      the void in primary production where seagrass beds disappear due to excessive
      nutrient enrichment. Sedimentary chl a (proxy of total microalgal biomass)
      significantly increased only during the June enrichment period, whereas
      fucoxanthin (proxy of total diatom biomass) was not increased by nutrient
      enrichment even though its concentration doubled in the enriched plots in June. 

PMID- 27041605
TI  - PHYLOGEOGRAPHY OF BATRACHOSPERMUM MACROSPORUM (BATRACHOSPERMALES, RHODOPHYTA)
      FROM NORTH AND SOUTH AMERICA(1).
AB  - Phylogeographic trends in Batrachospermum macrosporum Mont. were investigated
      using the mitochondrial intergenic spacer between the cytochrome oxidase subunit
      2 and 3 genes (cox2-3). A total of 11 stream segments were sampled with seven in
      the coastal plain of North America and four in tropical areas of South America.
      Fifteen thalli were sampled from seven streams, 14 thalli from two streams, and
      eight thalli from two streams. There were 16 haplotypes detected using 149
      individuals. Of the eight haplotypes from locations in North America, all were
      334 base pairs (bp) in length, and of those from South America, five were 344 bp,
      and three were 348 bp. Two individual networks were produced: one for the
      haplotypes from North America and another for those from South America, and these
      could not be joined due to the large number of base pair differences. This split
      between haplotypes from North and South America was confirmed with sequence data
      of the rbcL gene. There was very little genetic variation among the haplotypes
      from the North American locations, leading us to hypothesize that these are
      fairly recent colonization events along the coastal plain. In contrast, there was
      high variation among haplotypes from South America, and it would appear that the
      Amazon serves as a center of diversity. We detected considerable variation in
      haplotypes among streams, but frequently, a single haplotype in an individual
      stream segment, which is consistent with data from previous studies of other
      batrachospermalean taxa, may suggest a single colonization event per stream. 

PMID- 27041606
TI  - EVALUATION OF ANTIOXIDANT DEFENSE RESPONSES TO LEAD STRESS IN HAPALOSIPHON
      FONTINALIS-339(1).
AB  - Lead (Pb) is a heavy metal and a potentially hazardous environmental pollutant.
      In this study, the potential of lead to induce oxidative stress in biological
      systems was assessed using the cyanobacterium Hapalosiphon fontinalis-339 as
      model test organism. The impact of lead toxicity on the cellular antioxidant
      system and the biochemical modulations that result in generation of antioxidant
      defense responses were also studied. To determine the effect of Pb toxicity, the
      test organism was grown in the presence of various concentrations (0.05, 0.10,
      0.20, 0.40, 0.80, 1.0, 1.20, and 1.25 mg . L(-1) ) of exogenous lead chloride
      (PbCl2 ), and its effects on growth were observed in terms of the change in chl
      content. There was a significant increase in metal uptake by the alga with a
      concomitant decrease in growth. Lead stress appeared to significantly up-regulate
      the levels of stress-related antioxidant enzymes-such as superoxide dismutase
      (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR)-while a
      decrease in catalase (CAT) levels was observed. In addition, the levels of
      nonenzymatic antioxidants, oxidized and total glutathione, were changed. Our
      results suggest the existence of a potent antioxidant defense machinery in H.
      fontinalis-339 and this organism can be employed to monitor lead toxicity in the
      environment. 

PMID- 27041607
TI  - ABSENCE OF A LARGE BROWN MACROALGA ON URBANIZED ROCKY REEFS AROUND SYDNEY,
      AUSTRALIA, AND EVIDENCE FOR HISTORICAL DECLINE(1).
AB  - Loss of habitat-forming algae is increasingly prevalent in temperate marine
      ecosystems. Here, we document absence of an important habitat-forming macroalga,
      Phyllospora comosa (Labill.) C. Agardh, along an urbanized coast in New South
      Wales (NSW), Australia. Dense Phyllospora canopies were common on shallow
      sublittoral reefs north and south of Sydney. In contrast, we did not find a
      single individual along ~70 km of rocky coastline in the Sydney metropolitan
      region, despite historical evidence to suggest that it was very common half a
      century ago. Recolonization of this important habitat-forming alga has not
      occurred on Sydney reefs despite improved water quality, protection of its
      habitat, and frequent long-distance dispersal of Phyllospora wrack. While there
      are obvious limitations, historical information can be useful for identifying
      potential shifts in community structure to increase our understanding of
      contemporary ecological patterns. 

PMID- 27041608
TI  - INFLUENCE OF IRRADIANCE ON VIRUS-ALGAL HOST INTERACTIONS(1).
AB  - The effect of different irradiance levels on the interactions between the algal
      host and its virus was investigated for two marine phytoplankton, Phaeocystis
      globosa Scherff. and Micromonas pusilla (Butcher) Manton et Parke. The algal
      cultures were acclimated at 25, 100, and 250 MUmol photons . m(-2)  . s(-1) (LL,
      ML, and HL, respectively), after which they were infected with a lytic virus (PgV
      07T and MpV-02T) and monitored under the appropriate irradiance and in darkness.
      The effect of irradiance levels on the host-virus interactions differed for the
      two algal host-virus systems examined. For P. globosa, the LL-acclimated cultures
      showed a 4 h prolonged latent period (11-16 h), which may be related to the
      subsaturated growth observed at this irradiance. The burst size was reduced by
      50% at LL and HL compared to ML (525 PgV . cell(-1) ). The fraction of infectious
      viruses, however, remained unchanged. Viral replication was prevented when the LL
      P. globosa cultures were kept in darkness (up to 48 h) but recovered when placed
      back into the light. PgV-07T still replicated in the dark for the ML- and HL
      acclimated cultures, but viral yield was reduced by 50%-85%. For M. pusilla, the
      burst size (285-360 MpV . cell(-1) ), the infectivity, and the latent period of
      MpV-02T (7-11 h) remained unaffected by the incident light. Conversely, darkness
      not only inhibited MpV replication but also resulted in substantial cell lysis of
      the noninfected cultures. Our study implies that irradiance level is an important
      factor controlling algal host-virus interactions and hence the dynamics of
      phytoplankton populations. 

PMID- 27041609
TI  - PREDATION BY THE TOXIC DINOFLAGELLATE DINOPHYSIS FORTII ON THE CILIATE MYRIONECTA
      RUBRA AND OBSERVATION OF SEQUESTRATION OF CILIATE CHLOROPLASTS(1).
AB  - This is the first report of the propagation of the toxic dinoflagellate
      Dinophysis fortii Pavill. under laboratory conditions when fed on the marine
      ciliate Myrionecta rubra grown with the cryptophyte Teleaulax amphioxeia (W.
      Conrad) D. R. A. Hill. In contrast, reduced growth of D. fortii (max. of 3-4
      divisions) and formation of small cells were observed in the absence of the
      ciliate or when provided with T. amphioxeia only as prey, showing that D. fortii
      cannot utilize T. amphioxeia as prey. In the TEM observation of D. fortii cells,
      which had fully fed on the ciliate prey, well-developed chloroplasts (5-12 MUm in
      length) were seen and three thylakoids were usually arranged in most of the
      chloroplasts observed, but chloroplasts having two thylakoids were sometimes
      confirmed. In cells starved for 4 weeks, decrease of chloroplast numbers and
      disappearance of large chloroplasts were observed, and only a few small
      chloroplasts (0.5-2 MUm in length) remained in the marginal regions. In the
      observation of the sequestration process of the chloroplasts ingested from M.
      rubra by D. fortii, within 15 min after D. fortii captured M. rubra,
      incorporation of almost all of the chloroplasts was observed, while most of the
      other cell contents still remained in the M. rubra cell. After that, dispersion
      of the ingested chloroplasts toward the marginal regions was confirmed,
      suggesting that chloroplasts of M. rubra are ingested and dispersed in D. fortii
      cells in advance of the ingestion of the other cell contents to prevent them from
      being digested in food vacuoles. The ingested chloroplasts can also function as
      kleptoplastids. 

PMID- 27041610
TI  - BACTERIA-INDUCED MOTILITY REDUCTION IN LINGULODINIUM POLYEDRUM (DINOPHYCEAE)(1).
AB  - Biotic factors that affect phytoplankton physiology and behavior are not well
      characterized but probably play a crucial role in regulating their population
      dynamics in nature. We document evidence that some marine bacteria can decrease
      the swimming speed of motile phytoplankton through the release of putative
      protease(s). Using the dinoflagellate Lingulodinium polyedrum (F. Stein) J. D.
      Dodge as a model system, we showed that the motility-reducing components of
      bacterial-algal cocultures were mostly heat labile, were of high molecular weight
      (>50 kDa), and could be partially neutralized by incubations with protease
      inhibitors. We further showed that additions of the purified protease pronase E
      decreased dinoflagellate swimming speed in a concentration-dependent manner. We
      propose that motility can be used as a marker for dinoflagellate stress or
      general unhealthy status due to proteolytic bacteria, among other factors. 

PMID- 27041611
TI  - DIAZOTROPHIC GROWTH OF THE MARINE CYANOBACTERIUM TRICHODESMIUM IMS101 IN
      CONTINUOUS CULTURE: EFFECTS OF GROWTH RATE ON N2 -FIXATION RATE, BIOMASS, AND
      C:N:P STOICHIOMETRY(1).
AB  - Trichodesmium N2 fixation has been studied for decades in situ and, recently, in
      controlled laboratory conditions; yet N2 -fixation rate estimates still vary
      widely. This variance has made it difficult to accurately estimate the input of
      new nitrogen (N) by Trichodesmium to the oligotrophic gyres of the world ocean.
      Field and culture studies demonstrate that trace metal limitation, phosphate
      availability, the preferential uptake of combined N, light intensity, and
      temperature may all affect N2 fixation, but the interactions between growth rate
      and N2 fixation have not been well characterized in this marine diazotroph. To
      determine the effects of growth rate on N2 fixation, we established phosphorus
      (P)-limited continuous cultures of Trichodesmium, which we maintained at nine
      steady-state growth rates ranging from 0.27 to 0.67 d(-1) . As growth rate
      increased, biomass (measured as particulate N) decreased, and N2 -fixation rate
      increased linearly. The carbon to nitrogen ratio (C:N) varied from 5.5 to 6.2,
      with a mean of 5.8 +/- 0.2 (mean +/- SD, N = 9), and decreased significantly with
      growth rate. The N:P ratio varied from 23.4 to 45.9, with a mean of 30.5 +/- 6.6
      (mean +/- SD, N = 9), and remained relatively constant over the range of growth
      rates studied. Relative constancy of C:N:P ratios suggests a tight coupling
      between the uptake of these three macronutrients and steady-state growth across
      the range of growth rates. Our work demonstrates that growth rate must be
      considered when planning studies of the effects of environmental factors on N2
      fixation and when modeling the impact of Trichodesmium as a source of new N to
      oligotrophic regions of the ocean. 

PMID- 27041612
TI  - INVOLVEMENT OF INDOLE-3-ACETIC ACID PRODUCED BY THE GROWTH-PROMOTING BACTERIUM
      AZOSPIRILLUM SPP. IN PROMOTING GROWTH OF CHLORELLA VULGARIS(1).
AB  - Involvement of indole-3-acetic acid (IAA), produced by the microalgae-growth
      promoting bacteria Azospirillum brasilens and A. lipoferum, in promoting growth
      of the microalga Chlorella vulgaris Beij. was studied. Four wildtype strains of
      Azospirillum and their IAA-deficient mutants were co-immobilized with C. vulgaris
      in alginate beads. Cultures were grown in synthetic growth medium supplemented
      with tryptophan. Growth promotion of microalgae and production of exogenous IAA
      by Azospirillum spp. were monitored. All wildtype Azospirillum spp. produced
      significant but varying amounts of IAA, while their mutant forms produced
      significantly less. The results demonstrated a significant growth promotion in
      Chlorella cultures when immobilized with the four wildtype strains of
      Azospirillum, while very low or no enhanced growth was induced by the four IAA
      deficient mutants, compared to when C. vulgaris is immobilized alone. A
      complementation experiment, where an IAA-attenuated mutant (A. brasilense
      SpM7918) was supplemented with IAA produced by its parental wildtype strain (A.
      brasilense Sp6), restored growth promotion in the microalgae-mutant culture. 

PMID- 27041613
TI  - PHOTOSYNTHESIS AND PRODUCTION OF HYDROGEN PEROXIDE BY SYMBIODINIUM (PYRRHOPHYTA)
      PHYLOTYPES WITH DIFFERENT THERMAL TOLERANCES(1).
AB  - Occurrences whereby cnidaria lose their symbiotic dinoflagellate microalgae
      (Symbiodinium spp.) are increasing in frequency and intensity. These so-called
      bleaching events are most often related to an increase in water temperature,
      which is thought to limit certain Symbiodinium phylotypes from effectively
      dissipating absorbed excitation energy that is otherwise used for photochemistry.
      Here, we examined photosynthetic characteristics and hydrogen peroxide (H2 O2 )
      production, a possible signal involved in bleaching, from two Symbiodinium types
      (a thermally "tolerant" A1 and "sensitive" B1) representative of cnidaria
      Symbiodinium symbioses of reef-building Caribbean corals. Under steady-state
      growth at 26 degrees C, a higher efficiency of PSII photochemistry, rate of
      electron turnover, and rate of O2 production were observed for type A1 than for
      B1. The two types responded very differently to a period of elevated temperature
      (32 degrees C): type A1 increased light-driven O2 consumption but not the amount
      of H2 O2 produced; in contrast, type B1 increased the amount of H2 O2 produced
      without an increase in light-driven O2 consumption. Therefore, our results are
      consistent with previous suggestions that the thermal tolerance of Symbiodinium
      is related to adaptive constraints associated with photosynthesis and that
      sensitive phylotypes are more prone to H2 O2 production. Understanding these
      adaptive differences in the genus Symbiodinium will be crucial if we are to
      interpret the response of symbiotic associations, including reef-building corals,
      to environmental change. 

PMID- 27041614
TI  - OXIDATIVE STRESS RESPONSES IN THE MARINE ANTARCTIC DIATOM CHAETOCEROS BREVIS
      (BACILLARIOPHYCEAE) DURING PHOTOACCLIMATION(1).
AB  - The enzyme superoxide dismutase (SOD) holds a key position in the microalgal
      antioxidant network. The present research focused on oxidative stress responses
      in the Antarctic diatom Chaetoceros brevis F. Schutt during transition to excess
      (including ultraviolet radiation [UVR]) and limiting irradiance conditions. Over
      a 4 d period, cellular responses of thiobarbituric acid reactive substances
      (TBARS, a general oxidative stress indicator), SOD activity, photosynthetic and
      xanthophyll cycle pigments, PSII efficiency, and growth were determined. In
      addition, oxidative responses were measured during a daily cycle. Changing
      irradiance conditions significantly affected growth rates of C. brevis. PSII
      efficiency decreased significantly during periodic excess irradiance and
      increased under low irradiance conditions. Transition to excess irradiance
      increased the ratio of xanthophyll to light-harvesting pigments, whereas the
      opposite was observed for cultures transferred to low irradiance. This
      acclimation process was completed after 2 d in the new irradiance environment.
      SOD activity increased significantly after the first day regardless of the new
      irradiance environment but returned to preexposure values on the fourth day. We
      hypothesize that SOD activity may be temporarily elevated in C. brevis after
      irradiance shifts, thereby reducing oxidative stress when photoacclimation is in
      progress. 

PMID- 27041615
TI  - THE ROLE OF NITRIC OXIDE IN DIATOM ADHESION IN RELATION TO SUBSTRATUM
      PROPERTIES(1).
AB  - Adhesion of raphid diatoms to surfaces, mediated by the secretion of
      extracellular polymeric substances (EPS), is an important strategy for growth and
      survival. Diatom biofilms are also important in the context of biofouling.
      Diatoms exhibit selectivity in adhering to surfaces, but little is understood
      about how they perceive the properties of a substratum and translate that
      perception into altered adhesion properties. In this study, we demonstrate that
      Seminavis robusta Danielidis et D. G. Mann, like many other pennate diatoms,
      adheres more strongly to hydrophobic surfaces (such as silicone elastomer foul
      release coatings) than to hydrophilic surfaces. To explore the cellular
      mechanisms that may underlie this selectivity, we tested the hypothesis that
      diatoms may perceive a hydrophilic surface as unconducive to adhesion through a
      form of stress response involving nitric oxide (NO) production. Single-cell
      imaging with the fluorescent indicator DAF-FM DA (4-amino-5-methylamino-2',7'
      difluorofluorescein diacetate), revealed NO levels that were 4-fold higher in
      cells adhered to a hydrophilic surface (acid-washed glass) compared with a
      hydrophobic surface (polydimethylsiloxane elastomer, PDMSE). Elevated levels of
      NO caused by the addition of the NO donor S-nitroso-N-acetylpenicillamine (SNAP)
      did not affect growth, but cells showed reduced adhesion strength to both glass
      and PDMSE. Addition of the nitric oxide synthase inhibitor NG-monomethyl-l
      arginine (NMMA) caused a small but significant increase in adhesion strength.
      Overall, the results suggest that NO acts as a signal of the wettability
      properties of substrata for Seminavis. 

PMID- 27041616
TI  - ORIGIN OF APOMICTIC RED ALGAE: OUTCROSSING STUDIES OF DIFFERENT STRAINS IN
      CALOGLOSSA MONOSTICHA (CERAMIALES, RHODOPHYTA)(1).
AB  - Various red algae lack sexual reproduction and propagate by spore recycling, but
      it is still unknown how apomixis originates. In previous crossing experiments, we
      obtained an unusual hybrid of Caloglossa monosticha M. Kamiya through the
      outcrossing between a male from Australia and a female from Indonesia. This
      hybrid was morphologically identical to a normal tetrasporophyte, but its
      tetraspores grew into tetrasporophytes and repeated tetraspore recycling. During
      5 years of culture, no sexual reproductive structures have formed on the
      tetrasporelings from this hybrid or its progenies. Further hybridization
      experiments revealed that all the five female strains from Indonesia successfully
      crossed with the male strain from the East Alligator River, Australia, and most
      of the F1 sporophytes demonstrated tetraspore recycling, though the germination
      rates of these tetraspores were quite low. The ploidy level of the hybrid
      tetrasporophyte was similar to the normal tetrasporophyte, rather than the
      parental gametophyte, based on the comparison of relative DNA contents of their
      nuclei. Single strand conformation polymorphism (SSCP) and sequence analyses of
      the internal transcribed spacer 1 (ITS1) region indicated that the alleles from
      both parents were present in all the hybrid tetrasporophytes examined. These
      results suggest that this hybrid does not carry out meiosis during sporogenesis,
      and heterozygous diploid sporophytes arose from tetraspores. Therefore, we
      believe that obligate apomixis was generated through outcrossing between
      genetically different entities of C. monosticha. 

PMID- 27041617
TI  - MOLECULAR PHYLOGENY OF PHYCOCYANIN-CONTAINING CRYPTOPHYTES: EVOLUTION OF
      BILIPROTEINS AND GEOGRAPHICAL DISTRIBUTION(1).
AB  - Of 34 strains assigned to the cryptophyte genera Chroomonas Hansg., Hemiselmis
      Parke, and Komma D. R. A. Hill, distribution patterns of biliproteins, habitats,
      and sampling sites across a phylogenetic tree have been examined. The combined
      data set assembled from nuclear SSU rDNA, partial nuclear LSU rDNA, and
      nucleomorph SSU rDNA sequences comprised 4,083 positions and yielded an almost
      completely resolved tree. Spectrophotometry of the biliproteins and mapping of
      the different types of biliproteins onto the phylogenetic tree unveiled a complex
      evolutionary history. Different from other cryptophyte clades, the types of
      biliproteins were not generally congruent with clades or subclades of the genera
      Chroomonas (paraphyletic, phycocyanins [PCs] 645 or 630), Hemiselmis (PCs 612,
      630 or phycoerythrin [PE] 555), and Komma (PC 645). At least one putative
      character reversal took place in the genus Chroomonas. Several changes in
      biliproteins have been found in the genus Hemiselmis, including two new
      biliprotein variants that probably originated by slight modifications from PC 612
      and PE 555, respectively (PC 577 and PE 545/555). Freshwater and marine/brackish
      taxa were intermingled across the tree without displaying a specific pattern. In
      four terminal clades, genetically identical strains have been found to occur both
      in Europe and in the USA. The Chroomonas/Hemiselmis/Komma clade proved to be the
      most diverse of all cryptophyte clades concerning types of biliproteins and
      distribution of clades across marine or freshwater habitats. 

PMID- 27041618
TI  - PHYLOGENY OF THE EUGLENALES INFERRED FROM PLASTID LSU rDNA SEQUENCES(1).
AB  - To gain insights into the phylogeny of the Euglenales, we analyzed the plastid
      LSU rDNA sequences from 101 strains of the photosynthetic euglenoids belonging to
      nine ingroup genera (Euglena, Trachelomonas, Strombomonas, Monomorphina,
      Cryptoglena, Colacium, Discoplastis, Phacus, and Lepocinclis) and two outgroup
      genera (Eutreptia and Eutreptiella). Bayesian and maximum-likelihood (ML)
      analyses resulted in trees of similar topologies and four major clades: a Phacus
      and Lepocinclis clade; a Colacium clade; a Trachelomonas, Strombomonas,
      Monomorphina, and Cryptoglena clade; and a Euglena clade. The Phacus and
      Lepocinclis clade was the sister group of all other euglenalian genera, followed
      by Discoplastis spathirhyncha (Skuja) Triemer and the Colacium clade,
      respectively, which was inconsistent with their placement based on nuclear rDNA
      genes. The Trachelomonas, Strombomonas, Monomorphina, and Cryptoglena clade was
      sister to the Euglena clade. The loricate genera, Trachelomonas and Strombomonas,
      were closely related to each other, while Monomorphina and Cryptoglena also
      grouped together. The Euglena clade formed a monophyletic lineage comprising most
      species from taxa formerly allocated to the subgenera Calliglena and Euglena.
      However, within this genus, none of the subgenera was monophyletic. 

PMID- 27041619
TI  - TWO SNOW SPECIES OF THE QUADRIFLAGELLATE GREEN ALGA CHLAINOMONAS (CHLOROPHYTA,
      VOLVOCALES): ULTRASTRUCTURE AND PHYLOGENETIC POSITION WITHIN THE CHLOROMONAS
      CLADE(1).
AB  - The quadriflagellate snow alga Chlainomonas Christen, distributed in New Zealand
      and North America, has several unusual structural attributes. A process assumed
      to be cytokinesis involves extrusion of protoplasm from the parent through a
      narrow canal, C. kolii (J. T. Hardy et Curl) Hoham produces a net-like outer
      envelope rather than a cell wall, and the flagellar basal apparatus of
      Chlainomonas consists of two semi-independent pairs of basal bodies. Structural
      connections between basal body pairs appear minimal, but a connecting system
      different from that observed in other genera exists within each pair.
      Phylogenetic analysis using rbcL sequences places Chlainomonas in the Chloromonas
      clade, other known members of which are all biflagellate. Chlainomonas is split
      into two robust lineages, with New Zealand collections sharing an origin with
      northern North American collections. Although the quadriflagellate condition is
      regarded as ancestral in the Chlorophyceae, we speculate-based on ultrastructural
      and molecular data presented here-that Chlainomonas represents a derived form
      that has arisen from fusion of two ancestral biflagellate cells. Other
      explanations (for example, that Chlainomonas represents a diploid form of a
      biflagellate species) are remotely possible but are presently at odds with
      extensive observations of field material. Improvements in techniques for
      experimental manipulation of these sensitive cryophiles will be required to fully
      characterize their structure and progress our understanding of their biology. 

PMID- 27041620
TI  - MORPHOLOGY AND MOLECULAR PHYLOGENY OF AUREOPHYCUS ALEUTICUS GEN. ET SP. NOV.
      (LAMINARIALES, PHAEOPHYCEAE) FROM THE ALEUTIAN ISLANDS(1).
AB  - A previously unknown species of kelp was collected on Kagamil Island, Aleutian
      Islands. The species can be easily distinguished from any known laminarialean
      alga: the erect sporophytic thallus is composed of a thin lanceolate blade
      attaining ~2 m in height and ~0.50 m in width, without midrib, and the edge of
      the blade at the transition zone is thickened to form a V-shape; the stipe is
      solid and flattened, slightly translucent, attaining ~1 m in length; the holdfast
      is semidiscoidal and up to 0.15 m in diameter. Anatomically, the blade has the
      typical trumpet-shaped hyphae characteristic of the Chordaceae and derived
      foliose laminarialean species (i.e., Alariaceae/Laminariaceae/Lessoniaceae). No
      hair pits or mucilaginous structures were observed on the blade or stipe. No
      fertile sporophytes were collected, but abundant juvenile sporophytes were
      observed in the field. In the molecular phylogenetic analyses using chloroplast
      rbcL gene, nuclear ITS1-5.8S-ITS2 rDNA, and mitochondria nad6 DNA sequences, the
      new species (Aureophycus aleuticus gen. et sp. nov.) showed a closer relationship
      with Alariaceae of conventional taxonomy, or the "Group 1" clade of Lane et al.
      (2006) including Alaria and related taxa than with other groups, although the
      species was not clearly included in the group. Aureophycus may be a key species
      in elucidating the evolution of the Alariaceae within the Laminariales. Because
      of the lack of information on reproductive organs and insufficient resolution of
      the molecular analyses, we refrain from assigning the new species to a family,
      but we place the new species in a new genus in the Laminariales. 

PMID- 27041621
TI  - GRACILARIOPSIS MCLACHLANII SP. NOV. AND GRACILARIOPSIS PERSICA SP. NOV. OF THE
      GRACILARIACEAE (GRACILARIALES, RHODOPHYCEAE) FROM THE INDIAN OCEAN(1).
AB  - Two new species of Gracilariopsis from the Indian Ocean are proposed
      Gracilariopsis (Gp.) mclachlanii Buriyo, Bellorin et M. C. Oliveira sp. nov. from
      Tanzania and Gracilariopsis persica Bellorin, Sohrabipour et E. C. Oliveira sp.
      nov. from Iran-based on morphology and DNA sequence data (rbcL gene and SSU
      rDNA). Both species fit the typical features of Gracilariopsis: axes cylindrical
      throughout, freely and loosely ramified up to four orders, with an abrupt
      transition in cell size from medulla to cortex, cystocarps lacking tubular
      nutritive cells and superficial spermatangia. Nucleotide sequence comparisons of
      rbcL and SSU rDNA placed both species into the Gracilariopsis clade as distinct
      species from all the accepted species for this genus, forming a deeply divergent
      lineage together with some species from the Pacific. The new species are very
      difficult to distinguish on morphological grounds from other species of
      Gracilariopsis, stressing the importance of homologous molecular marker
      comparisons for the species recognition in this character-poor genus. 

PMID- 27041622
TI  - PHYLOGENETIC RELATIONSHIPS AMONG LINEAGES OF THE CERAMIACEAE (CERAMIALES,
      RHODOPHYTA) BASED ON NUCLEAR SMALL SUBUNIT rDNA SEQUENCE DATA(1).
AB  - Phylogenetic relationships among 69 species of the Ceramiales (51 Ceramiaceae,
      six Dasyaceae, seven Delesseriaceae, and five Rhodomelaceae) were determined
      based on nuclear SSU rDNA sequence data. We resolved five strongly supported but
      divergent lineages among the included Ceramiaceae: (i) the genus Inkyuleea, which
      weakly joins other orders of the Rhodymeniophycidae rather than the Ceramiales in
      our analyses; (ii) the tribe Spyridieae, which is sister to the remainder of the
      included ceramialean taxa; (iii) the subfamily Ceramioideae, weakly including the
      tribe Warrenieae; (iv) the subfamily Callithamnioideae; and (v) the subfamily
      Compsothamnioideae, which emerges as sister to the
      Dasyaceae/Delesseriaceae/Rhodomelaceae complex, thus rendering the Ceramiaceae
      sensu lato unequivocally paraphyletic, as has been argued separately on
      anatomical grounds by Kylin and Hommersand. Our data support a restricted concept
      of the Ceramiaceae that includes only one of the five lineages (Ceramioideae)
      that we have resolved. In addition to failing to ally with the Ceramiales in our
      molecular analyses, species of Inkyuleea differ substantially from other
      Ceramiaceae sensu lato in details of pre- and postfertilization development. The
      genus Inkyuleea is here assigned to the Inkyuleeaceae fam. nov., which we
      provisionally retain in the Ceramiales. Species of Spyridia also differ from the
      remaining Ceramiaceae in their postfertilization development, and, in light of
      our molecular data, the genus Spyridia is assigned to the Spyridiaceae. The
      Callithamnioideae is strongly monophyletic (100% in all analyses), which, in
      combination with key anatomical differences, supports elevation to family status
      for this lineage as the Callithamniaceae. Similarly, the Compsothamnioideae is
      solidly monophyletic in our molecular trees and has a unique suite of defining
      anatomical characters that supports family status for a complex that we consider
      to include the tribes Compsothamnieae, Dasyphileae, Griffithsieae, Monosporeae,
      Ptiloteae, Spermothamnieae, Sphondylothamnieae, Spongoclonieae, and Wrangelieae,
      for which the reinstated family name Wrangeliaceae is available. 

PMID- 27041623
TI  - PHYLOGENETIC PATTERNS AMONG NOSTOC CYANOBIONTS WITHIN BI- AND TRIPARTITE LICHENS
      OF THE GENUS PANNARIA(1).
AB  - Phylogenetic relationships between Nostoc cyanobionts in the lichen genus
      Pannaria were studied to evaluate their correlation to geography, habitat
      ecology, and other patterns previously reported. The 16S rRNA gene sequences of a
      total of 37 samples of 21 Pannaria species from seven countries from the Northern
      and Southern hemispheres were analyzed and compared with 69 free-living and
      symbiotic cyanobacterial strains. The sequences from Pannaria were distributed
      throughout a branch of Nostoc sequences previously called "the Nephroma guild,"
      and within two subgroups from another branch, referred to as the "Peltigera
      guild," although there was a gradual transition between the two major groups.
      There is a more diverse pattern of relationships between Nostoc sequences from
      bipartite versus tripartite lichen species in Pannaria, compared with other well
      studied genera, such as Nephroma and Peltigera. Cyanobionts from several
      tripartite Pannaria species from the Southern Hemisphere and corticolous
      bipartite species from both hemispheres were grouped together. Four sequences of
      Pannaria and Pseudocyphellaria cyanobionts from rocks in the Chilean Juan
      Fernandez Islands were nested within corticolous cyanobionts, whereas the
      terricolous "Pannaria sphinctrina clade" was placed with other terricolous
      strains. The cluster patterns derived from phylogenetic analysis were partly
      reflecting lichen taxonomy, in two groups of lichen species, possibly indicating
      coevolution. The phylogram partly also reflected lichen ecology. Three Pannaria
      species have very different cyanobiont strains when they grow in different
      habitats. 

PMID- 27041624
TI  - COOLIA CANARIENSIS SP. NOV. (DINOPHYCEAE), A NEW NONTOXIC EPIPHYTIC BENTHIC
      DINOFLAGELLATE FROM THE CANARY ISLANDS(1).
AB  - A new photosynthetic dinoflagellate species, Coolia canariensis S. Fraga sp.
      nov., is described based on samples taken from tidal ponds on the rocky shore of
      the Canary Islands, northeast Atlantic Ocean. Its morphology was studied by LM
      and SEM. It is almost spherical and has a thick smooth theca with many scattered
      pores. Plate 1' is the biggest of the epithecal plates, and 7" is twice as wide
      as it is long. Phylogeny inferred from the D1/D2 regions of the LSU nuclear rDNA
      of three strains of C. canariensis and several strains of other Coolia species,
      C. monotis, C. sp., showed that C. canariensis strains clustered in a well
      supported clade distinct from the other species. No toxins were detected using
      mouse bioassay, liquid chromatography with Fluorescence detection (LC-FLD) or
      liquid chromatography-mass spectrometry (LC-MS). Its pigment composition is of
      the peridinin type of dinoflagellates. Together with this new species, many other
      strains of C. monotis from the Atlantic Ocean and Mediterranean Sea have been
      analyzed for toxin presence, and no evidence of toxin production related to
      yessotoxins (YTXs) was found, as was previously suggested for C. monotis from
      Australia. 

PMID- 27041625
TI  - ACCLIMATION TO LOW TEMPERATURE OF TWO ARTHROSPIRA PLATENSIS (CYANOBACTERIA)
      STRAINS INVOLVES DOWN-REGULATION OF PSII AND IMPROVED RESISTANCE TO
      PHOTOINHIBITION(1).
AB  - This study aimed to compare the ability of two Arthrospira platensis (Nordst.)
      Gomont strains, M2 and Kenya, isolated from two different habitats, to acclimate
      to low temperature (15 degrees C). Both strains had similar growth rates at 30
      degrees C, but once acclimated to low temperature, M2 showed a greater decline in
      growth (59% vs. 41% in the Kenya strain). We suggest that the Kenya strain
      acclimated better to low temperature by down-regulating its photosynthetic
      activity through (i) decreasing antenna size and thus reducing energy flux into
      the photosystems; (ii) decreasing reaction center density (RC/CSX ) and the
      performance index, thus decreasing the trapping probability and electron
      transport rate while maintaining electron transport probability for electron
      transport beyond QA (-) unchanged; (iii) increasing the energy dissipation flux.
      In contrast, the M2 strain showed no difference in antenna size and exhibited a
      much lower decrease in RC/CSX and a lower dissipation rate. Hence, the Kenya
      strain minimized potential damage on the acceptor side of PSII compared to the M2
      cells. Furthermore, acclimation to low temperature was accompanied by an improved
      mechanism for handling excess energy resulting in an enhanced ability of the
      Kenya strain to rapidly repair damaged PSII RCs and withstand a high photon flux
      density (HPFD) stress; this finding might be defined as a cross-adaptation
      phenomenon. This study may provide a tool to identify strains suitable for
      outdoor mass-production in different regions characterized by different climate
      conditions. 

PMID- 27041626
TI  - GROWTH DYNAMICS OF ULVA ROTUNDATA (CHLOROPHYTA) IN A FISH FARM: IMPLICATIONS FOR
      BIOMITIGATION AT A LARGE SCALE(1).
AB  - Changes in biomass of several macroalgae [Ulva rotundata Bliding; Gracilariopsis
      longissima (S. G. Gmel.) Steentoft, L. M. Irvine et Farnham; Ulva intestinalis
      L.; and Cladophora sp.] and marine plants (Zostera noltii and Ruppia cirrhosa)
      growing naturally in earthen ponds of a fish farm (Acuinova, San Fernando,
      Southern Spain) were recorded during a year. The farm is mainly devoted to the
      culture of gilthered seabream (Sparus aurata). The most conspicuous algal species
      thriving in the ponds was U. rotundata, which reached densities up to 600 g dry
      mass . m(-2) and produced up to 20.45 g C . m(-2)  . d(-1) . Dissolved nutrients
      (phosphate and ammonium), tissue nutrient content, and growth rates of this
      species were estimated during 2001 and 2002. Evidence of natural biomitigation by
      U. rotundata when water circulates throughout the fish farm is presented. Due to
      the fish cultivation, both phosphate and ammonium increased as water circulated
      from the preculture ponds to the postculture ponds. As a consequence, U.
      rotundata tissue nitrogen (N) and phosphorus (P) increased from algae growing in
      preculture ponds to algae growing in the outflow channel, so that mean C:N:P
      ratio varied from 773:57:1 in preculture ponds to 567:64:1 in the outflow
      channel. Phosphorus limited growth of U. rotundata during the spring. As growth
      rates increased as a function of tissue P, data were fitted to the Droop
      equation. From this equation, the estimated maximal growth rate was 0.295 +/-
      0.041 d(-1) , the subsistence quota was 0.05 +/- 0.01% P of dry mass, and the
      critical quota was 0.215% P of dry mass. The results suggest that management of
      the fish farm based on a large-scale integrated mariculture system of fish and
      macroalgae may increase the total ecological and economic benefits, both for the
      farm and for the environment. 

PMID- 27041627
TI  - CULTURE OF THE HETEROTROPHIC DINOFLAGELLATE PROTOPERIDINIUM CRASSIPES
      (DINOPHYCEAE) WITH NONCELLULAR FOOD ITEMS(1).
AB  - The genus Protoperidinium is an assemblage of heterotrophic dinoflagellates,
      several species of which have been successfully cultured in the past using
      various photosynthetic algae as a food source. We succeeded in culturing
      Protoperidinium crassipes (Kof.) Balech on three separate occasions for periods
      ranging from 2 to 21 months using rice flour as a food source. In these cultures,
      unusual small types of cells that were never observed to actively feed sometimes
      appeared. We confirmed that P. crassipes in culture exhibited bioluminescence. 

PMID- 27041628
TI  - The feasibility of indocyanine green fluorescence imaging for identifying and
      assessing the perfusion of parathyroid glands during total thyroidectomy.
AB  - BACKGROUND: There are limited adjuncts available for identifying and assessing
      the viability of parathyroid glands (PGs) during total thyroidectomy (TT). The
      aim of this study is to determine the feasibility of indocyanine green (ICG)
      imaging in identifying and assessing perfusion of PGs during TT. METHODS: ICG was
      administered in patients undergoing TT and fluorescence of PGs was assessed. A
      grading scale was developed for assessing degree of ICG uptake. Patients were
      evaluated for hypocalcemia and hypoparathyroidism on post-operative day (POD) #1.
      RESULTS: Twenty-seven patients underwent TT with ICG imaging for multinodular
      goiter (n = 13), thyroid cancer (n = 10), and Graves' disease (n = 4). Eight-five
      PGs were identified visually, 71 (84%) of which showed ICG fluorescence. False
      negative rate was 6%. Post-operatively, three patients (11%) had a serum calcium
      value <8 mg/dl. ICG uptake after TT correlated with post-operative PTH levels:
      mean POD#1 PTH of those patients with at least two PGs exhibiting <30%
      fluorescence was 9 pg/ml; whereas those with fewer than two demonstrating <30%
      fluorescence had a POD#1 PTH of 19.5 pg/ml (P = 0.05). CONCLUSION: ICG imaging of
      PGs during TT is feasible. ICG might be a useful adjunct in identifying those
      patients at risk for post-thyroidectomy hypoparathyroidism. J. Surg. Oncol.
      2016;113:775-778. (c) 2016 Wiley Periodicals, Inc.

PMID- 27041629
TI  - Machining characteristics of the haversian and plexiform components of bovine
      cortical bone.
AB  - This paper investigates the characteristic differences observed while machining
      the haversian and plexiform components of a bovine cortical femoral bone. To this
      end micro-milling slotting experiments are performed on both the components by
      varying both the cutting velocity and the feed-per-tooth values. The scale of
      machining is chosen specifically to ensure sensitivity to the microstructural
      variations in the bone. The material properties of the microstructural components
      and their size-scale relative to the feed-per-tooth values are seen to dictate
      the failure mechanisms encountered during machining. The cutting force, surface
      roughness, and tool wear are all uniquely affected by the plexiform and haversian
      components of the cortical bone. In general, plexiform bone requires a higher
      cutting force than the haversian bone. While a higher cutting velocity can lower
      the surface roughness of haversian bone, it typically results in the most surface
      damage. The cutting force and surface roughness values for both the components
      show strain rate sensitivity. The tool wear is seen to be the highest while
      cutting parallel to the lamellar structures seen in the plexiform bone.

PMID- 27041630
TI  - Surgical Intervention for Instability of the Craniovertebral Junction.
AB  - Surgical approaches for stabilizing the craniovertebral junction (CVJ) are
      classified as either anterior or posterior approaches. Among the anterior
      approaches, the established method is anterior odontoid screw fixation. Posterior
      approaches are classified as either atlanto-axial fixation or occipito-cervical
      (O-C) fixation. Spinal instrumentation using anchor screws and rods has become a
      popular method for posterior cervical fixation. Because this method achieves
      greater stability and higher success rates for fusion without the risk of
      sublaminar wiring, it has become a substitute for previous methods that used bone
      grafting and wiring. Several types of anchor screws are available, including C1/2
      transarticular, C1 lateral mass, C2 pedicle, and translaminar screws. Appropriate
      anchor screws should be selected according to characteristics such as technical
      feasibility, safety, and strength. With these stronger anchor screws, shorter
      fixation has become possible. The present review discusses the current status of
      surgical interventions for stabilizing the CVJ. 

PMID- 27041631
TI  - Shunt Devices for the Treatment of Adult Hydrocephalus: Recent Progress and
      Characteristics.
AB  - Various types of shunt valves have been developed during the past 50 years, most
      of which can be classified into the following categories: (1) fixed differential
      pressure valves; (2) fixed differential pressure (DP) valves with an antisiphon
      mechanism; (3) programmable DP valves; (4) programmable DP valves with an
      antisiphon mechanism; and (5) programmable antisiphon valves. When considering
      the myriad of possible postoperative condition changes, such as the onset of
      accidental non-related diseases or trauma in adults, and changes in normal
      physiological development or anticipation of future shunt removal in children, it
      has become standard to use the programmable valve as a first choice for
      cerebrospinal fluid shunting. However, it is still unclear what type of shunt
      valve is suitable for each individual case. Based on the results of SINPHONI and
      more recently SINPHONI 2 trials, the programmable DP valve is recommended as the
      first line shunt valve. The programmable DP valve with an antisiphon mechanism is
      thought to be beneficial for tall, slender patients, who have a tendency for
      easily developing complications of overdrainage, however, this type of valve must
      be used cautiously in obese patients because of the increased risk of
      underdrainage. Although the current evidence is still insufficient, the
      programmable antisiphon valve, which costs the same as the programmable DP valve,
      is also thought to be the first line shunt valve. The quick reference table is
      applicable for most shunt valves, and for patients with either the
      ventriculoperitoneal or the lumboperitoneal shunt. 

PMID- 27041632
TI  - Recent Progress in Endothelial Progenitor Cell Culture Systems: Potential for
      Stroke Therapy.
AB  - Endothelial progenitor cells (EPCs) participate in endothelial repair and
      angiogenesis due to their abilities to differentiate into endothelial cells and
      to secrete protective cytokines and growth factors. Consequently, there is
      considerable interest in cell therapy with EPCs isolated from peripheral blood to
      treat various ischemic injuries. Quality and quantity-controlled culture systems
      to obtain mononuclear cells enriched in EPCs with well-defined angiogenic and
      anti-inflammatory phenotypes have recently been developed, and increasing
      evidence from animal models and clinical trials supports the idea that
      transplantation of EPCs contributes to the regenerative process in ischemic
      organs and is effective for the therapy of ischemic cerebral injury. Here, we
      briefly describe the general characteristics of EPCs, and we review recent
      developments in culture systems and applications of EPCs and EPC-enriched cell
      populations to treat ischemic stroke. 

PMID- 27041633
TI  - Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia Using a Single-Plane,
      Flat Panel Detector Angiography System: Technical Note.
AB  - Percutaneous treatments for trigeminal neuralgia (TN) including glycerol
      rhizotomy (GR), radiofrequency thermocoagulation (RT), and balloon compression
      (BC) are effective for patients with medical comorbidities and risk factors of
      microvascular decompression (MVD). These procedures are usually performed under
      fluoroscopy. Surgeons advance the needle to the trigeminal plexus through the
      foramen ovale while observing landmarks of fluoroscopic images; however, it is
      sometimes difficult to appropriately place the needle tip in Meckel's cave. We
      present the technical details of percutaneous GR using a single-plane, flat panel
      detector angiography system to check the needle positioning. When the needle tip
      may be located near the trigeminal cistern, three-dimensional (3-D) bone images
      are taken with cone-beam computed tomography (CT). These images clearly show the
      position of the needle tip in Meckel's cave. If it is difficult to place it
      through the foramen ovale, surgeons perform cone beam CT to observe the actual
      position of the needle tip at the skull base. After confirming the positional
      relation between the needle tip and foramen ovale, surgeons can advance it in the
      precise direction. In 10 procedures, we could place the nerve-block needle in
      about 14.5 minutes on average without complications. We think that our method is
      simple and convenient for percutaneous treatments for TN, and it may be helpful
      for surgeons to perform such treatments. 

PMID- 27041634
TI  - Basic liver immunology.

PMID- 27041636
TI  - Immunological functions of liver sinusoidal endothelial cells.
AB  - Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and separate
      passenger leukocytes in the sinusoidal lumen from hepatocytes. LSECs further act
      as a platform for adhesion of various liver-resident immune cell populations such
      as Kupffer cells, innate lymphoid cells or liver dendritic cells. In addition to
      having an extraordinary scavenger function, LSECs possess potent immune
      functions, serving as sentinel cells to detect microbial infection through
      pattern recognition receptor activation and as antigen (cross)-presenting cells.
      LSECs cross-prime naive CD8 T cells, causing their rapid differentiation into
      memory T cells that relocate to secondary lymphoid tissues and provide protection
      when they re-encounter the antigen during microbial infection. Cross-presentation
      of viral antigens by LSECs derived from infected hepatocytes triggers local
      activation of effector CD8 T cells and thereby assures hepatic immune
      surveillance. The immune function of LSECs complements conventional immune
      activating mechanisms to accommodate optimal immune surveillance against
      infectious microorganisms while preserving the integrity of the liver as a
      metabolic organ.

PMID- 27041635
TI  - Aberrant coagulation causes a hyper-inflammatory response in severe influenza
      pneumonia.
AB  - Influenza A virus (IAV) infects the respiratory tract in humans and causes
      significant morbidity and mortality worldwide each year. Aggressive inflammation,
      known as a cytokine storm, is thought to cause most of the damage in the lungs
      during IAV infection. Dysfunctional coagulation is a common complication in
      pathogenic influenza, manifested by lung endothelial activation, vascular leak,
      disseminated intravascular coagulation and pulmonary microembolism. Importantly,
      emerging evidence shows that an uncontrolled coagulation system, including both
      the cellular (endothelial cells and platelets) and protein (coagulation factors,
      anticoagulants and fibrinolysis proteases) components, contributes to the
      pathogenesis of influenza by augmenting viral replication and immune
      pathogenesis. In this review, we focus on the underlying mechanisms of the
      dysfunctional coagulatory response in the pathogenesis of IAV.

PMID- 27041637
TI  - CD205-TLR9-IL-12 axis contributes to CpG-induced oversensitive liver injury in
      HBsAg transgenic mice by promoting the interaction of NKT cells with Kupffer
      cells.
AB  - Gut-derived bacterial products contribute to liver inflammation and injury during
      chronic hepatitis B virus infection; however, the underlying mechanisms remain
      obscure. In this study, hepatitis B surface antigen transgenic (HBs-Tg) mice and
      their wild-type (WT) control C57BL/6 mice were injected with CpG
      oligodeoxynucleotides (ODNs) to mimic the translocation of gut microbial products
      into the systemic circulation. We found that, compared with the WT mice, the HBs
      Tg mice were oversensitive to CpG-ODN-induced liver injury, which was dependent
      on natural killer T (NKT) cells. CpG-ODN injection enhanced the expression of Fas
      ligand (FasL) on NKT cells. In addition, hepatocytes from the HBs-Tg mice
      expressed higher levels of Fas than did those from the WT mice, which was further
      augmented by CpG-ODN. Interaction of Fas and FasL was involved in the
      cytotoxicity of NKT cells against hepatocytes in the HBs-Tg mice. Moreover,
      Kupffer cells in the HBs-Tg mice expressed higher levels of CD205 and produced
      greater amounts of interleukin (IL)-12 than did those in the WT mice. Finally,
      the depletion of Kupffer cells, neutralization of IL-12 or specific silencing of
      CD205 on Kupffer cells significantly inhibited CpG-ODN-induced liver injury and
      NKT activation in the HBs-Tg mice. Our data suggest that CD205-expressing Kupffer
      cells respond to CpG-ODNs and subsequently release IL-12 to promote NKT cell
      activation. Activated NKT cells induce liver damage through the Fas signaling
      pathway in HBs-Tg mice.

PMID- 27041639
TI  - [Female sexual dysfunction: Drug treatment options].
AB  - Many women will likely experience a sexual problem in their lifetime. Female
      sexual dysfunction is a broad term used to describe 3 categories of disorders of
      a multifactorial nature. Effective, but limited pharmacotherapeutic options exist
      to address female sexual dysfunction. The FDA recently approved the first agent
      for treatment of hypoactive sexual desire disorder in pre-menopausal women. Off
      label use of hormonal therapies, particularly oestrogen and testosterone, are the
      most widely employed for female sexual dysfunction, particularly in post
      menopausal women. Other drugs currently under investigation include
      phosphodiesterase inhibitors and agents that modulate dopamine or melanocortin
      receptors. 

PMID- 27041640
TI  - [Provisional considerations about Zika virus infection in pregnant women:
      Document for health professionals].

PMID- 27041638
TI  - Modulation of liver tolerance by conventional and nonconventional antigen
      presenting cells and regulatory immune cells.
AB  - The liver is a tolerogenic organ with exquisite mechanisms of immune regulation
      that ensure upkeep of local and systemic immune tolerance to self and foreign
      antigens, but that is also able to mount effective immune responses against
      pathogens. The immune privilege of liver allografts was recognized first in pigs
      in spite of major histo-compatibility complex mismatch, and termed the "liver
      tolerance effect". Furthermore, liver transplants are spontaneously accepted with
      only low-dose immunosuppression, and induce tolerance for non-hepatic co
      transplanted allografts of the same donor. Although this immunotolerogenic
      environment is favorable in the setting of organ transplantation, it is
      detrimental in chronic infectious liver diseases like hepatitis B or C, malaria,
      schistosomiasis or tumorigenesis, leading to pathogen persistence and weak anti
      tumor effects. The liver is a primary site of T-cell activation, but it elicits
      poor or incomplete activation of T cells, leading to their abortive activation,
      exhaustion, suppression of their effector function and early death. This is
      exploited by pathogens and can impair pathogen control and clearance or allow
      tumor growth. Hepatic priming of T cells is mediated by a number of local
      conventional and nonconventional antigen-presenting cells (APCs), which promote
      tolerance by immune deviation, induction of T-cell anergy or apoptosis, and
      generating and expanding regulatory T cells. This review will focus on the
      communication between classical and nonclassical APCs and lymphocytes in the
      liver in tolerance induction and will discuss recent insights into the role of
      innate lymphocytes in this process.

PMID- 27041641
TI  - [Hypertrophic osteoarthropathy in lung adenocarcinoma].

PMID- 27041642
TI  - Cobicistat Significantly Increases Tacrolimus Serum Concentrations in a Renal
      Transplant Recipient with Human Immunodeficiency Virus Infection.
AB  - Cobicistat is a pharmacokinetic booster in several fixed-dose combination
      products for treatment of human immunodeficiency virus (HIV) infection. As a
      potent inhibitor of cytochrome P450 (CYP) 3A enzymes, significant drug-drug
      interactions are expected between cobicistat and medications that are metabolized
      primarily through the CYP3A pathway, including calcineurin inhibitors (e.g.,
      tacrolimus and cyclosporine). We describe a case of tacrolimus toxicity due to
      supratherapeutic tacrolimus concentrations when Stribild (elvitegravir,
      cobicistat, emtricitabine, and tenofovir disoproxil fumarate) was initiated for
      newly diagnosed HIV infection in a 50-year-old renal transplant recipient who was
      previously receiving a stable tacrolimus regimen. Drug-drug interaction via CYP3A
      inhibition was acknowledged, and weekly labs were ordered to allow for close
      monitoring of renal function and tacrolimus serum concentrations as recommended
      by Stribild prescribing information. The patient reported headache, insomnia,
      stomachache, and decreased urine output within 1 week of starting Stribild and
      was found to have acute kidney injury (serum creatinine [Scr ]concentration
      increasing from 1.5-2.3 mg/dl) and a serum tacrolimus concentration of 111.2
      ng/ml at 1 week follow-up (goal trough level 4-6 ng/ml). Both tacrolimus and
      Stribild were withheld. In 15 days, the patient's tacrolimus serum concentration
      returned to goal. In the interim, he required twice/week clinic visits for
      laboratory assessments and an emergency department visit for management of
      hyperkalemia (potassium 6.5 mEq/L). Triumeq (abacavir, dolutegravir, and
      lamivudine) was started about 4 weeks later after Scr returned to baseline, and
      his tacrolimus serum trough concentrations subsequently remained stable. To our
      knowledge, this is the first case report describing the extent, significance, and
      onset of cobicistat and tacrolimus drug-drug interaction in clinical practice. As
      more fixed-dose combination products including cobicistat as a pharmacokinetic
      booster come to market, clinicians should be reminded of its multitude of
      clinically significant drug-drug interactions.

PMID- 27041643
TI  - Quercetin inhibits angiogenesis by targeting calcineurin in the xenograft model
      of human breast cancer.
AB  - Vascular endothelial growth factor receptor 2 (VEGFR2) mediated
      calcineurin/nuclear factor of activated T-cells (NFAT) pathway is crucial in the
      angiogenesis of human breast cancer. Quercetin (Qu), a flavonoid known to possess
      anti-angiogenesis and antitumor properties, inhibited calcineurin activity in
      vitro. Herein, we performed a study in vivo to evaluate the effects of Qu on the
      angiogenesis in breast cancer. Female BALB/c nude mice were injected with MCF-7
      cells into the mammary fat and were randomly divided into four groups. The
      animals were treated with vehicle solution, tamoxifen (TAM, 5.6mg/kg), tacrolimus
      (FK506, 3mg/kg), or Qu (34mg/kg) for 21 days, respectively. The results showed
      that, similar to TAM and FK506, Qu decreased tumor growth, limited oncocyte
      proliferation and promoted tumor necrosis. Anti-angiogenic actions of Qu were
      demonstrated as decreased serum VEGF (P<0.01), and sparse microvessel density
      (P<0.05). Qu significantly inhibited tumor calcineurin activities, and the
      inhibitory rate was 62.73% in Qu treated animals, compared to that was 72.90% in
      FK506 group (P>0.05). Effects of Qu on calcineurin/NFAT pathway were confirmed as
      decreased subcellular located levels of VEGF (P<0.05), VEGFR2 (P<0.05) and NFATc3
      (P<0.01), downregulated gene expression of VEGF (P<0.05), VEGFR2 (P<0.05) and
      NFATc3 (P<0.01), reduced protein levels of VEGF (P<0.05), VEGFR2 (P<0.05), and
      NFATc3 (P<0.01) in tumor tissues. These findings indicate that Qu inhibit
      angiogenesis of human breast cancer xenograft in nude mice, which was associated
      with suppressing calcineurin activity and its regulated pathway activation. 

PMID- 27041644
TI  - Dietary n-3 long chain polyunsaturated fatty acids in allergy prevention and
      asthma treatment.
AB  - The rise in non-communicable diseases, such as allergies, in westernized
      countries links to changes in lifestyle and diet. N-3 long chain polyunsaturated
      fatty acids (LCPUFA) present in marine oils facilitate a favorable milieu for
      immune maturation and may contribute to allergy prevention. N-3 LCPUFA can
      suppress innate and adaptive immune activation and induce epigenetic changes.
      Murine studies convincingly show protective effects of fish oil, a source of n-3
      LCPUFA, in food allergy and asthma models. Observational studies in human
      indicate that high dietary intake of n-3 LCPUFA and low intake of n-6 PUFA may
      protect against the development of allergic disease early in life. High n-6 PUFA
      intake is also associated with an increased asthma risk while n-3 LCPUFA may be
      protective and reduce symptoms. The quality of the marine oil used has impact on
      efficacy of allergy prevention and several observations link in particular n-3
      LCPUFA DHA to allergy suppression. Randomized controlled trials indicate that
      optimal timing, duration and dosage of n-3 LC-PUFA is required to exert an
      allergy protective effect. Supplementation during early pregnancy and lactation
      has shown promising results regarding allergy prevention. However these findings
      should be confirmed in a larger cohort. Although clinical trials in asthma
      patients reveal no consistent clinical benefits of n-3 LCPUFA supplementation on
      lung function, it can suppress airway inflammation. Future food-pharma approaches
      may reveal whether adjunct therapy with dietary n-3 LCPUFA can improve allergy
      prevention or immunotherapy via support of allergen specific oral tolerance
      induction or contribute to the efficacy of drug therapy for asthma patients. 

PMID- 27041645
TI  - Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney
      injury through alpha2C-adrenoceptors in rats.
AB  - Excitation of renal sympathetic nervous activity and the resulting increased
      levels of renal venous norepinephrine play important roles in renal
      ischaemia/reperfusion injury in rats. This study examined the effects of
      yohimbine, a non-selective alpha2-adrenoceptor antagonist, on renal venous
      norepinephrine levels and kidney function in acute kidney injury. Acute
      ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the
      left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a
      contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min
      prior to ischaemia significantly attenuated kidney injury and decreased the renal
      venous norepinephrine levels, as compared with vehicle-treated rats. To
      investigate the involvement of alpha2-adrenoceptor subtypes, we pre-treated with
      JP-1302, a selective alpha2C-adrenoceptor antagonist (1mg/kg). This suppressed
      renal venous norepinephrine levels and tumour necrosis factor-alpha and monocyte
      chemoattractant protein-1 mRNA levels after reperfusion and improved kidney
      function. Pre-treatment with BRL44408, a selective alpha2A-adrenoceptor
      antagonist (1mg/kg), or imiloxan, a selective alpha2B-adrenoceptor antagonist
      (1mg/kg) had no effect on renal function or tissue injury. These results suggest
      that yohimbine prevented ischaemia/reperfusion-induced kidney injury by
      inhibiting alpha2C-adrenoceptors and suppressing pro-inflammatory cytokine
      expression. 

PMID- 27041646
TI  - Inhibition of acetyl-CoA carboxylases by soraphen A prevents lipid accumulation
      and adipocyte differentiation in 3T3-L1 cells.
AB  - Acetyl-CoA carboxylases (ACC) 1 and 2 catalyze the carboxylation of acetyl-CoA to
      malonyl-CoA and depend on biotin as a coenzyme. ACC1 localizes in the cytoplasm
      and produces malonyl-CoA for fatty acid (FA) synthesis. ACC2 localizes in the
      outer mitochondrial membrane and produces malonyl-CoA that inhibits FA import
      into mitochondria for subsequent oxidation. We hypothesized that ACCs are
      checkpoints in adipocyte differentiation and tested this hypothesis using the
      ACC1 and ACC2 inhibitor soraphen A (SA) in murine 3T3-L1 preadipocytes. When 3T3
      L1 cells were treated with 100nM SA for 8 days after induction of
      differentiation, the expression of PPARgamma mRNA and FABP4 mRNA decreased by 40%
      and 50%, respectively, compared with solvent controls; the decrease in gene
      expression was accompanied by a decrease in FABP4 protein expression and
      associated with a decrease in lipid droplet accumulation. The rate of FA
      oxidation was 300% greater in SA-treated cells compared with vehicle controls.
      Treatment with exogenous palmitate restored PPARgamma and FABP4 mRNA expression
      and FABP4 protein expression in SA-treated cells. In contrast, SA did not alter
      lipid accumulation if treatment was initiated on day eight after induction of
      differentiation. We conclude that loss of ACC1-dependent FA synthesis and loss of
      ACC2-dependent inhibition of FA oxidation prevent lipid accumulation in
      adipocytes and inhibit early stages of adipocyte differentiation. 

PMID- 27041647
TI  - The influence of dopaminergic system in medial prefrontal cortex on ketamine
      induced amnesia in passive avoidance task in mice.
AB  - Dopaminergic modulations of glutamate receptors are essential for the prefrontal
      cortical (PFC) behavioral and cognitive functions. In order to understand the
      effect of dopamine/glutamate interactions on learning and memory, we investigated
      the effects of intra medial prefrontal cortex (mPFC) injections of dopaminergic
      agents on ketamine-induced amnesia by using a one-trial passive avoidance task in
      mice. Pre-training administration of ketamine (5, 10 and 15mg/kg, i.p.) dose
      dependently decreased the memory acquisition of a one-trial passive avoidance
      task. Pre-training intra-mPFC administration of SKF 38393, D1 receptor agonist
      and quinpirol D2 receptor agonist, alone did not affect memory acquisition.
      However, amnesia induced by pre-training ketamine (15mg/kg) significantly
      decreased by pretreatment of SKF 38393 (2 and 4ug/mouse) and quinpirol (0.3, 1
      and 3ug/mouse). Pre-training administration of SCH 23390, D1 receptor antagonist
      (0.75 and 1MUg/mouse, intra-mPFC), and sulpiride D2 receptor antagonist
      (3MUg/mouse, intra-mPFC) impaired memory acquisition. In addition, co
      pretreatment of different doses of SCH 23390 and sulpiride with lower dose of
      ketamine (5mg/kg), which did not induce amnesia by itself, caused inhibition of
      memory formation. It may be concluded that dopaminergic system of medial
      prefrontal cortex is involved in the ketamine-induced impairment of memory
      acquisition. 

PMID- 27041648
TI  - Cell type dependent morphological adaptation in polyelectrolyte hydrogels governs
      chondrogenic fate.
AB  - Repair of critical-size articular cartilage defects typically involves delivery
      of cells in biodegradable, 3D matrices. Differences in the developmental status
      of mesenchymal stem cells (MSCs) and terminally differentiated mature
      chondrocytes might be a critical factor in engineering appropriate 3D matrices
      for articular cartilage tissue engineering. This study examined the relationship
      between material-driven early cell morphological adaptations and chondrogenic
      outcomes, by studying the influence of aligned collagen type I (Col I)
      presentation on chondrocytes and MSC in interfacial polyelectrolyte complexation
      (IPC)-based hydrogels. In the absence of Col I, both chondrocytes and MSCs
      adopted rounded cell morphology and formed clusters, with chondrocyte clusters
      favoring the maintenance of hyaline phenotype, while MSC clusters differentiated
      to fibro-superficial zone-like chondrocytes. Encapsulated chondrocytes in IPC-Col
      I hydrogel adopted a fibroblastic morphology forming fibro-superficial zone-like
      phenotype, which could be reversed by inhibiting actin polymerization using
      cytochalasin D (CytD). In contrast, adoption of fibroblastic morphology by
      encapsulated MSCs in IPC-Col I facilitated superior chondrogenesis, generating a
      mature, hyaline neocartilage tissue. CytD treatment abrogated the elongation of
      MSCs and brought about a single cell-like state, resulting in insignificant
      chondrogenic differentiation, underscoring the essential requirement of providing
      matrix environments that are amenable to cell-cell interactions for robust MSC
      chondrogenic differentiation. Our study demonstrates that MSCs and culture
      expanded chondrocytes favour differential microenvironmental niches and
      emphasizes the importance of designing biomaterials that meet cell type-specific
      requirements, in adopting chondrocyte or MSC-based approaches for regenerating
      hyaline, articular cartilage. 

PMID- 27041650
TI  - Chitosan/Sterculia striata polysaccharides nanocomplex as a potential chloroquine
      drug release device.
AB  - Nanoparticles are produced by means of polyelectrolyte complexation (PEC) of
      oppositely charged polycationic chitosan (CH) with polyanionic polysaccharide
      extracted from Sterculia striata exudates (rhamnogalacturonoglycan (RG)-type
      polysaccharide). The nanoparticles formed with low-molar-mass CH are larger than
      those formed with high-molar-mass CH. This behavior is in contrast with that
      previously observed for other systems and may be attributed to different
      mechanisms related to the association of CH with RG of higher persistence length
      chain than that of CH. Nanoparticles harnessed with a charge ratio (n(+)/n(-)) of
      <1 are smaller than particles with an excess of polycations. Particles with
      hydrodynamic sizes smaller than 100nm are achieved using a polyelectrolyte
      concentration of 10(-4)gmL(-1) and charge ratio (n(+)/n(-)) of <1. The CH/RG
      nanoparticles are associated with chloroquine (CQ) with an efficiency of 28% and
      release it for up to ~60% within ~10h, whereas in the latter, only ~40% of the CQ
      was released after 24h. The main factor that influenced drug release rate is the
      nanoparticle charge ratio. 

PMID- 27041649
TI  - Prolonged release of TGF-beta from polyelectrolyte nanoparticle loaded
      macroporous chitin-poly(caprolactone) scaffold for chondrogenesis.
AB  - Cartilage degeneration occurs when the catabolic factors overtakes the anabolic
      factors. The regeneration capability of damaged cartilage is poor due to its
      hypovascular and hypocellular tissue. Tissue engineering strategies aims in
      development of a suitable substrate that provide the required physical, chemical
      and biological cues to the proliferating cells to direct chondrogenesis. A
      macroporous polymeric blend scaffold of chitin and poly(caprolactone) (PCL) was
      fabricated by lyophilisation technique and characterized using Scanning Electron
      Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and
      Thermogravimetric/Differential thermal Analysis (TG/DTA). The effect of prolonged
      release of Transforming growth factor-beta (TGF-beta) was studied by
      encapsulating it in chondroitin sulphate nanoparticles (nCS) incorporated in
      chitin-PCL scaffold. Chondroitin sulphate nanoparticles containing TGF-beta (TGF
      beta-nCS) was developed by polyelectrolyte crosslinking using chitosan.
      Characterization of TGF-beta-nCS by Dynamic Light Scattering particle sizer and
      SEM showed a 230+/-20nm sized spherical particles. Swelling and degradation
      studies of the composite scaffold showed its stability. Protein adsorption was
      enhanced in nanoparticle containing scaffold. The effect of TGF-beta was well
      addressed by the increased attachment and proliferation of rabbit adipose derived
      mesenchymal stem cells (rASCs). The chondrogenic potential of rASCs in the
      presence of TGF-beta releasing composite scaffold showed an increased
      proteoglycan deposition. These studies highlight the positive effects of chitin
      PCL-TGF-beta-nCS scaffold for cartilage regeneration.

PMID- 27041651
TI  - N,N-dimethylhexadecyl carboxymethyl chitosan as a potential carrier agent for
      rotenone.
AB  - In this study, an amphiphilic chitosan derivative namely N,N-dimethylhexadecyl
      carboxymethyl chitosan (DCMC) was synthesised and applied for the first time as a
      carrier agent for rotenone. The physical and chemical properties of DCMC were
      characterised by using Fourier Transform Infrared Spectrometer (FTIR), Proton
      Nuclear Magnetic Resonance Spectrometer ((1)H NMR), CHN-O Elemental Analyser,
      Thermogravimetric Analyser (TGA) and Differential Scanning Calorimeter (DSC).
      DCMC was soluble in acidic (except pH 4), neutral and basic media with percent of
      transmittance (%T) values ranged from 67.2 to 99.4%. The critical micelle
      concentration (CMC) was determined as 0.095mg/mL. Transmission Electron
      Microscopy (TEM) analysis confirmed that DCMC has formed self-aggregates and
      exhibited spherical shape with the size of 65.5-137.0nm. The encapsulation
      efficiency (EE) and loading capacity (LC) of DCMC micelles with different weight
      ratios (DCMC:rotenone; 5:1, 50:1 and 100:1) were determined by using High
      Performance Liquid Chromatography (HPLC). The weight ratio of 100:1 gave the best
      EE with the value of more than 95.0%. DCMC micelles performed an excellent
      ability to control the release of rotenone, of which 99.0% of rotenone was
      released within 48h. Overall, DCMC has several key features to be an effective
      carrier agent for pesticide formulations. 

PMID- 27041652
TI  - Prevalence of Uterine Myomas Among Women with 2 or More Recurrent Pregnancy
      Losses: A Systematic Review.
AB  - Recurrent pregnancy loss (RPL), defined as 2 or more failed clinical pregnancies,
      affects approximately 5% of reproductive women. Several etiologies for RPL have
      been studied including uterine myomas. However, the effect of uterine myomas on
      pregnancy outcomes in this patient population remains unclear. The purpose of
      this systematic review was to critically appraise the evidence associating
      uterine myomas with RPL and quantify the prevalence of uterine myomas in this
      patient population. The inclusion criteria included women of reproductive age
      with at least 2 or more recurrent, failed clinical pregnancies found to have a
      submucosal and/or intramural myoma distorting the uterine cavity on a
      hysterosalpingogram, a saline infusion sonogram, and/or hysteroscopy. Studies
      with biochemical pregnancies; molar, ectopic, and pregnancies of unknown
      location; pregnancies conceived with assisted-reproductive technologies;
      therapeutic abortions; subserosal myomas and intramural myomas not distorting the
      uterine cavity; studies using only 2-dimensional pelvic ultrasound; or studies in
      which no additional workup for RPL was initiated or in which multiple etiologies
      were included were omitted from this review. Risk of bias and quality assessment
      were conducted using the Quality Assessment Tool for Observational Cohort and
      Cross-sectional studies published by the National Institutes of Health. The
      electronic search yielded 934 citations. After title, abstract, and full-text
      screening, 3 studies had met the pre-established inclusion/exclusion criteria and
      were included in the review. The prevalence of submucosal and cavity-distorting
      myomas in women with 2 or more pregnancy losses was found to be 4.08% (29/711).
      The prevalence of uterine myomas was highest in women with 3 or more RPLs (5.91%
      [28/473]). No studies with a proper control group were identified. In summary,
      the association between uterine myomas and RPL remains unclear. High-quality
      studies are required to assert the impact of uterine myomas on pregnancy outcomes
      in this patient population. Patients with RPL and uterine myomas should be
      properly counseled regarding the existing evidence before surgical consideration.

PMID- 27041653
TI  - Primary Vaginal Adenosarcoma With Sarcomatous Overgrowth Arising in Recurrent
      Endometriosis: Feasibility of Laparoscopic Treatment and Review of the
      Literature.
AB  - We report a case of a primary vaginal adenosarcoma with sarcomatous overgrowth in
      a postmenopausal 58-year-old woman with recurrent endometriosis. In the past 5
      years she underwent several biopsies of a polypoid lesion on the vaginal cuff,
      and the last histologic examination of the biopsy showed an adenosarcoma with
      "sarcomatous overgrowth" in a background of endometriosis. There was no evidence
      of distant metastatic disease on the diagnostic workup, and we performed a
      laparoscopy to remove the pelvic mass. We reviewed the literature on the
      electronic databases Medline, Embase, and Science Direct on articles published in
      English from 1990 to 2015. We identified 5 articles in which the surgical
      treatment was performed via a laparotomic approach. The present case is the first
      in the literature to report feasibility of laparoscopic treatment for this kind
      of pathology with a detailed description of the surgical technique.

PMID- 27041654
TI  - Nanowire growth kinetics in aberration corrected environmental transmission
      electron microscopy.
AB  - We visualize atomic level dynamics during Si nanowire growth using aberration
      corrected environmental transmission electron microscopy, and compare with lower
      pressure results from ultra-high vacuum microscopy. We discuss the importance of
      higher pressure observations for understanding growth mechanisms and describe
      protocols to minimize effects of the higher pressure background gas. 

PMID- 27041655
TI  - The diversity-disease relationship: evidence for and criticisms of the dilution
      effect.
AB  - The dilution effect, that high host species diversity can reduce disease risk,
      has attracted much attention in the context of global biodiversity decline and
      increasing disease emergence. Recent studies have criticized the generality of
      the dilution effect and argued that it only occurs under certain circumstances.
      Nevertheless, evidence for the existence of a dilution effect was reported in
      about 80% of the studies that addressed the diversity-disease relationship, and a
      recent meta-analysis found that the dilution effect is widespread. We here review
      supporting and critical studies, point out the causes underlying the current
      disputes. The dilution is expected to be strong when the competent host species
      tend to remain when species diversity declines, characterized as a negative
      relationship between species' reservoir competence and local extinction risk. We
      here conclude that most studies support a negative competence-extinction
      relationship. We then synthesize the current knowledge on how the diversity
      disease relationship can be modified by particular species in community, by the
      scales of analyses, and by the disease risk measures. We also highlight the
      complex role of habitat fragmentation in the diversity-disease relationship from
      epidemiological, evolutionary and ecological perspectives, and construct a
      synthetic framework integrating these three perspectives. We suggest that future
      studies should test the diversity-disease relationship across different scales
      and consider the multiple effects of landscape fragmentation.

PMID- 27041656
TI  - Laser ablation sample transfer for localized LC-MS/MS proteomic analysis of
      tissue.
AB  - We have developed a mid-infrared laser ablation sampling technique for nano-flow
      liquid chromatography coupled with tandem mass spectrometry proteomic profiling
      of discrete regions from biological samples. Laser ablation performed in
      transmission geometry was used to transfer material from 50-um thick tissue
      sections mounted on a glass microscope slide to a capturing solvent. Captured
      samples were processed using filter-aided sample preparation and enzymatically
      digested to produce tryptic peptides for data-dependent analysis with an ion trap
      mass spectrometer. Comparison with ultraviolet laser capture microdissection from
      neighboring regions on the same tissue section revealed that infrared laser
      ablation transfer has higher reproducibility between samples from different
      consecutive sections. Both techniques allowed for proteomics investigation of
      different organelles without the addition of surfactants.

PMID- 27041657
TI  - Photooxygenation and gas-phase reactivity of multiply threaded pseudorotaxanes.
AB  - The solution-phase photooxygenation of multiply threaded crown/ammonium
      pseudorotaxanes containing anthracene spacers is monitored by electrospray
      ionization Fourier-transform ion-cyclotron-resonance (ESI-FTICR) mass
      spectrometry. The oxygenated pseudorotaxanes are mass-selected and fragmented by
      infrared multiphoton dissociation (IRMPD) and/or collision-induced dissociation
      (CID) experiments and and their behavior compared to that of the non-oxygenated
      precursors. [4+2]Cycloreversion reactions lead to the loss of O2, when no other
      reaction channel with competitive energy demand is available. Thus, the release
      of molecular oxygen can serve as a reference reaction for the energy demand of
      other fragmentation reactions such as the dissociation of the crown/ammonium
      binding motifs. The photooxygenation induces curvature into the initially planar
      anthracene and thus significantly changes the geometry of the divalent,
      anthracene-spacered wheel. This is reflected in ion-mobility data. Coulomb
      repulsion in multiply charged pseudorotaxanes assists the oxygen loss as the re
      planarization of the anthracene increases the distance between the two charges.

PMID- 27041658
TI  - Structural Elucidation of beta-Lactam Diastereoisomers through Ion Mobility Mass
      Spectrometry Studies and Theoretical Calculations.
AB  - The ion mobility combined with mass spectrometry and theoretical calculations
      were used to characterize and separate six diastereoisomeric beta-lactams. The
      influence of traveling wave height and wave velocity, size of the alkali metal
      ion (Li(+), Na(+) and K(+)) and drift gases with varying masses and
      polarizabilities (N2 and CO2) on separation efficacy was additionally examined.
      The best separation of diastereoisomers of beta-lactams was observed for adducts
      with Na(+) and Li(+) ions, whereas other parameters had little impact on
      separation process. The isomeric beta-lactams were characterized by both
      experimental and theoretical collision cross sections. The theoretically
      calculated values of collision cross sections obtained from extensive molecular
      dynamics and density functional theory calculations for model structures agreed
      well with those established experimentally. The relationship between separation
      efficacy and the configuration at the carbon atoms C5 and C6 of beta-lactam ring
      was defined.

PMID- 27041659
TI  - Quantum dots assisted laser desorption/ionization mass spectrometric detection of
      carbohydrates: qualitative and quantitative analysis.
AB  - A quantum dots (QDs) assisted laser desorption/ionization mass spectrometric (QDA
      LDI-MS) strategy was proposed for qualitative and quantitative analysis of a
      series of carbohydrates. The adsorption of carbohydrates on the modified surface
      of different QDs as the matrices depended mainly on the formation of hydrogen
      bonding, which led to higher MS intensity than those with conventional organic
      matrix. The effects of QDs concentration and sample preparation method were
      explored for improving the selective ionization process and the detection
      sensitivity. The proposed approach offered a new dimension to the application of
      QDs as matrices for MALDI-MS research of carbohydrates. It could be used for
      quantitative measurement of glucose concentration in human serum with good
      performance. The QDs served as a matrix showed the advantages of low background,
      higher sensitivity, convenient sample preparation and excellent stability under
      vacuum. The QDs assisted LDI-MS approach has promising application to the
      analysis of carbohydrates in complex biological samples.

PMID- 27041660
TI  - Detection of polydimethylsiloxanes transferred from silicone-coated parchment
      paper to baked goods using direct analysis in real time mass spectrometry.
AB  - The non-stick properties of parchment papers are achieved by polydimethylsiloxane
      (PDMS) coatings. During baking, PDMS can thus be extracted from the silicone
      coated parchment into the baked goods. Positive-ion direct analysis in real time
      (DART) mass spectrometry (MS) is highly efficient for the analysis of PDMS. A
      DART-SVP source was coupled to a quadrupole-time-of-flight mass spectrometer to
      detect PDMS on the contact surface of baked goods after use of silicone-coated
      parchment papers. DART spectra from the bottom surface of baked cookies and
      pizzas exhibited signals because of PDMS ions of the general formula [(C2H6SiO)n 
      + NH4 ](+) in the m/z 800-1900 range.

PMID- 27041661
TI  - Branched glycosylated inositolphosphosphingolipid structures in plants revealed
      by MS(3) analysis.

PMID- 27041662
TI  - Thermal degradation of beta-carotene studied by ion mobility atmospheric solid
      analysis probe mass spectrometry: full product pattern and selective ionization
      enhancement.
AB  - Atmospheric solid analysis probe mass spectrometry has the capability of
      capturing full product patterns simultaneously including both volatile and semi
      volatile compounds produced at elevated temperatures. Real-time low-energy
      collision-induced fragmentation combined with ion mobility separations enables
      rapid identification of the chemical structures of products. We present here for
      the first time the recognition of full product patterns resulting from the
      thermal degradation of beta-carotene at temperatures up to 600  degrees C.
      Solvent vapor-induced ionization enhancement is observed, which reveals parallel
      thermal dissociation processes that lead to even- and odd-numbered mass products.
      The drift-time distributions of high mass products, along with beta-carotene,
      were monitored with temperature, showing multiple conformations that are
      associated with the presence of two beta-rings. Products of masses 346/347,
      however, show a single conformation distribution, which indicates the separation
      of two beta-rings resulting from the direct bond scission at the polyene
      hydrocarbon chain. The thermal degradation pathways are evaluated and discussed.

PMID- 27041663
TI  - Preparing to read the ubiquitin code: characterization of ubiquitin trimers by
      top-down mass spectrometry.
AB  - The profound effects of ubiquitination on the movement and processing of cellular
      proteins depend exquisitely on the structures of monoubiquitin and polyubiquitin
      modifications. Unconjugated polyubiquitins also have a variety of intracellular
      functions. Structures and functions are not well correlated yet, because the
      structures of polyubiquitins and polyubiquitin modifications of proteins are
      difficult to decipher. We are moving towards a robust strategy to provide that
      structural information. In this report electron transfer dissociation mass
      spectra of six synthetic ubiquitin trimers (multiply branched proteins with
      molecular masses exceeding 25,600 Da) are examined using an Orbitrap Fusion Lumos
      instrument to determine how top-down mass spectrometry can characterize the chain
      topology and linkage sites in a single, facile workflow. The efficacy of this
      method relies on the formation, detection, and interpretation of extensive
      fragmentation.

PMID- 27041665
TI  - In vitro effects of metals on isolated head-kidney and blood leucocytes of the
      teleost fish Sparus aurata L. and Dicentrarchus labrax L.
AB  - The in vitro use of fish leucocytes to test the toxicity of aquatic pollutants,
      and particularly the immutoxicological effects, could be a valuable alternative
      to fish bioassays but has received little attention. In this study, head-kidney
      and peripheral blood leucocytes (HKLs and PBLs, respectively) from gilthead
      seabream (Sparus aurata L.) and European sea bass (Dicentrarchus labrax L.)
      specimens were exposed to Cd, MeHg (methylmercury), Pb or As for 24 h being
      evaluated the resulting cytotoxicity. Exposure to metals produced a dose
      dependent reduction in the viability, and MeHg showed the highest toxicity
      followed by Cd, As and Pb. Interestingly, leucocytes from European sea bass are
      more resistant to metal exposure than those from gilthead seabream. Similarly,
      HKLs are always more sensitive than those isolated from blood from the same fish
      species. Moreover, fish leucocytes incubated with metals exhibited alterations in
      gene expression profiles that were more pronounced in the HKLs in general, being
      Pb the metal provoking less effects. Concretely, genes related to cellular
      protection (metallothionein), stress (heat shock protein 70) and oxidative stress
      (superoxide dismutase, catalase and glutathione reductase) were, in general, down
      regulated in seabream HKLs but up-regulated in seabream PBLs and sea bass HKLs
      and PBLs. In addition, this profile leads to the increase of expression in genes
      related to apoptosis (Bcl2 associated X protein and caspase 3). Finally,
      transcription of genes involved in immunity (interleukin-1beta and immunoglobulin
      M) was down-regulated, mainly in seabream leucocytes. This study points to the
      benefits for evaluating the toxicological mechanisms of marine pollution using
      fish leucocytes in vitro and insight into the mechanisms at gene level. 

PMID- 27041666
TI  - Genome wide identification of scavenger receptors class A in common carp
      (Cyprinus carpio) and their expression following Aeromonas hydrophila infection.
AB  - Scavenger receptors class A (SCARAs) is a subgroup of diverse families of pattern
      recognition receptors that bind a range of ligands, and play important roles in
      innate immune processes through pathogens detection, adhesion, endocytosis, and
      phagocytosis. However, most studies of SCARAs have focused on mammals, and much
      less is known of SCARAs in fish species. In this study, we identified 7 SCARAs
      across the common carp genome, which were classified into four subclasses
      according to comparative genomic analysis including sequence similarities
      analysis, gene structure and functional domain prediction. Further phylogenetic
      and syntenic analysis supported their annotation and orthologies. Through
      examining gene copy number of SCARA genes across several vertebrates, SCARA2,
      SCARA3 and SCARA4 were found have undergone gene duplication. The expression
      patterns of SCARAs in common carp were examined during early developmental
      stages, in healthy tissues, and after Aeromonas hydrophila infection. Most SCARA
      genes were ubiquitously expressed during common carp early developmental stages,
      and presented diverse patterns in various healthy tissues, with relatively high
      expression levels in spleen, liver, intestine, gill and brain, indicating their
      critical roles likely in maintaining homeostasis and host immune response
      activities. After A. hydrophila infection, most SCARA genes were up-regulated at
      4 h post infection in mucosal tissue intestine, while generally up-regulated at
      12 h post infection in spleen, suggesting a tissue-specific pattern of
      regulation. Taken together, all these results suggested that SCARA genes played
      important roles in host immune response to A. hydrophila infection in common
      carp, and provided important genomic resources for future studies on fish disease
      management. 

PMID- 27041668
TI  - Microelectrode characterization of coral daytime interior pH and carbonate
      chemistry.
AB  - Reliably predicting how coral calcification may respond to ocean acidification
      and warming depends on our understanding of coral calcification mechanisms.
      However, the concentration and speciation of dissolved inorganic carbon (DIC)
      inside corals remain unclear, as only pH has been measured while a necessary
      second parameter to constrain carbonate chemistry has been missing. Here we
      report the first carbonate ion concentration ([CO3(2-)]) measurements together
      with pH inside corals during the light period. We observe sharp increases in
      [CO3(2-)] and pH from the gastric cavity to the calcifying fluid, confirming the
      existence of a proton (H(+)) pumping mechanism. We also show that corals can
      achieve a high aragonite saturation state (Omegaarag) in the calcifying fluid by
      elevating pH while at the same time keeping [DIC] low. Such a mechanism may
      require less H(+)-pumping and energy for upregulating pH compared with the high
      [DIC] scenario and thus may allow corals to be more resistant to climate change
      related stressors. 

PMID- 27041667
TI  - beta-naphthoflavone interferes with cyp1c1, cox2 and IL-8 gene transcription and
      leukotriene B4 secretion in Atlantic cod (Gadus morhua) head kidney cells during
      inflammation.
AB  - The objective of this study was to evaluate how beta-naphthoflavone interacts
      with lipopolysaccharide (LPS) and polyinosinic acid: polycytidylic acid (poly I:
      C) induced innate immune parameters as well as phase I and phase II
      detoxification enzymes in head kidney cells isolated from Atlantic cod. beta
      naphthoflavone is a pure agonist of aryl hydrocarbon receptor (AhR) while LPS and
      poly I: C are not. beta-naphthoflavone was added to head kidney leukocytes alone
      or together with LPS or poly I: C and the responses were evaluated in terms of
      protein and gene expression. The results showed that beta-naphthoflavone (25 nM),
      with and without LPS, significantly induced cytochrome P450 (cyp1c) transcription
      in cod head kidney cells. beta-naphthoflavone (100 nM) in the presence of the
      virus mimic, poly I: C, also increased cyp1c1transcription. LPS induced cyp1c1,
      cyclooxygenase 2 (cox2), interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and
      interleukin 8 (IL-8) transcription, genes that were not affected by the tested
      beta-naphthoflavone concentrations alone. However, beta-naphthoflavone (25 and 50
      nM) strengthened LPS induced cox2 and IL-8 transcription. Cod head kidney cells
      exposed to beta-naphthoflavone concentrations ranging from 25 to 100 nM, with and
      without LPS or poly I: C, expressed AhR protein. LPS or beta-naphthoflavone (5-50
      nM) significantly induced leukotriene B4 (LTB4) secretion compared to control. In
      conclusion, this study suggests that beta-naphthoflavone could interfere with LPS
      induced immune cell signaling in cod head kidney cells. 

PMID- 27041669
TI  - InGaN nanowires with high InN molar fraction: growth, structural and optical
      properties.
AB  - The structural and optical properties of axial GaN/InGaN/GaN nanowire
      heterostructures with high InN molar fractions grown by molecular beam epitaxy
      have been studied at the nanoscale by a combination of electron microscopy,
      extended x-ray absorption fine structure and nano-cathodoluminescence techniques.
      InN molar fractions up to 50% have been successfully incorporated without
      extended defects, as evidence of nanowire potentialities for practical device
      realisation in such a composition range. Taking advantage of the N-polarity of
      the self-nucleated GaN NWs grown by molecular beam epitaxy on Si(111), the N
      polar InGaN stability temperature diagram has been experimentally determined and
      found to extend to a higher temperature than its metal-polar counterpart.
      Furthermore, annealing of GaN-capped InGaN NWs up to 800  degrees C has been
      found to result in a 20 times increase of photoluminescence intensity, which is
      assigned to point defect curing. 

PMID- 27041670
TI  - [Acute-phase reactants in daptomycin induced pneumonia].

PMID- 27041671
TI  - Genome-wide assessment of differential translations with ribosome profiling data.
AB  - The closely regulated process of mRNA translation is crucial for precise control
      of protein abundance and quality. Ribosome profiling, a combination of ribosome
      foot-printing and RNA deep sequencing, has been used in a large variety of
      studies to quantify genome-wide mRNA translation. Here, we developed Xtail, an
      analysis pipeline tailored for ribosome profiling data that comprehensively and
      accurately identifies differentially translated genes in pairwise comparisons.
      Applied on simulated and real datasets, Xtail exhibits high sensitivity with
      minimal false-positive rates, outperforming existing methods in the accuracy of
      quantifying differential translations. With published ribosome profiling
      datasets, Xtail does not only reveal differentially translated genes that make
      biological sense, but also uncovers new events of differential translation in
      human cancer cells on mTOR signalling perturbation and in human primary
      macrophages on interferon gamma (IFN-gamma) treatment. This demonstrates the
      value of Xtail in providing novel insights into the molecular mechanisms that
      involve translational dysregulations. 

PMID- 27041672
TI  - BRCAness is beneficial for indicating triple negative breast cancer patients
      resistant to taxane.
AB  - AIM: Triple negative breast cancer (TNBC) is a heterogeneous disease and is
      associated with the cancer stem cell (CSC), basal-like, and BRCA1 function
      deficient (BRCAness) subtypes. We examined these 3 subtypes in TNBC and compared
      their chemosensitivity against anthracycline or taxane with a special attention
      to BRCAness. METHODS: Sixty-six TNBC cases were obtained from a randomized phase
      II trial comparing TCx6 (TC6) with FEC-Docetaxel (FEC-D) as neoadjuvant
      chemotherapy. The core needle specimens before chemotherapy were used for
      subtyping. The basal-like and CSC subtypes were identified by
      immunohistochemistry; CK5/6 and EGFR staining for the basal-like subtype and
      ALDH1 staining for the CSC subtype. The BRCAness subtype was examined by
      Multiplex Ligation-dependent Probe Amplification (MLPA). Correlations between
      subgroups and pCR rates according to each regimen and subtype were examined.
      RESULTS: The basal-like and BRCAness subtypes were significantly associated (p =
      0.010) with the other subtypes, but not the CSC subtype. The pCR rates were
      higher with FEC-D than with TC6 in the basal-like (54.5% vs 14.3%, p = 0.081) and
      BRCAness (56.2% vs 16.7%, p = 0.030) subtypes. Both were not effective in the CSC
      subtype (18.2% vs 11.8%, p = 1.00). CONCLUSION: BRCAness identified by MLPA was
      practically useful for treatment selection for avoiding taxane. ALDH1 may be
      considered as a marker for the CSC subtype requiring novel agents.

PMID- 27041673
TI  - A conversation analytic study of patterns of overlapping talk in conversations
      between individuals with dementia and their frequent communication partners.
AB  - BACKGROUND: Difficulty participating in conversation is commonly experienced by
      individuals with dementia, secondary to cognitive and language deficits. Frequent
      communication partners (FCPs), however, report being largely unaware of how to
      support their conversation partners with dementia during conversation. In
      particular, taking a turn appropriately may be difficult for either partner due
      to trouble predicting a partner's behaviour and, hence, difficulty with timing
      conversational turns appropriately, potentially resulting in overlapping talk.
      AIMS: To investigate the patterns of overlapping talk in the interaction between
      individuals with dementia and their FCPs. METHODS & PROCEDURES: Three
      participants with moderate-severe dementia participated in conversation with an
      FCP. Ten minutes of 'casual' and 'task-oriented' conversation were audio- and
      video-recorded. Patterns of overlapping talk were investigated using conversation
      analytic methods. OUTCOMES & RESULTS: Overlapping talk was a consistent feature
      of all three dyadic interactions during both social and task-oriented talk. All
      participants exhibited competitive and non-competitive forms of overlapping talk.
      The data reveal that FCPs commonly yielded their own turns when overlapped by a
      partner in order to create opportunities for their partners with dementia to
      communicate. Participants with dementia demonstrated some retained pragmatic
      abilities, both using continuers and yielding the floor to their partner when
      competitively overlapped in order to encourage a speaker to continue. CONCLUSIONS
      & IMPLICATIONS: These findings contribute to the understanding of the impact of
      dementia on the maintenance of sensitivity to the sequential aspects of everyday
      talk. From a clinical perspective, these findings can inform the training of FCPs
      about retained abilities and evidence-based support strategies, equipping them
      with knowledge and skills to structure and maintain fluent conversation.

PMID- 27041675
TI  - A confirmatory factor analysis of the MATRICS consensus cognitive battery in
      severe mental illness.
AB  - BACKGROUND: A recent factor analysis of Measurement and Treatment Research to
      Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)
      data in a sample of schizophrenia-spectrum patients described a three factor
      model representing processing speed, attention/working memory, and learning; the
      social cognition measure was excluded from the analysis. The current analyses
      sought to replicate a three factor structure of the MCCB in a larger, more
      diagnostically diverse sample of participants. METHODS: Confirmatory factor
      analyses were performed to evaluate the factor structure of the MCCB in 300
      outpatients with severe mental illness (54.3% schizophrenia-spectrum diagnoses)
      who were participants in three studies of cognitive remediation. Exploratory
      analyses were conducted to evaluate the concurrent prediction of symptoms from
      MCCB factor scores. RESULTS: The three factor structure of the MCCB demonstrated
      stronger model fit (chi(2)=14.53, p=0.75, SRMR=0.02, RMSEA=0.0, CFI=1.00,
      NNFI=1.01) than the unifactoral structure. Poorer cognitive performance across
      all three MCCB factors was significantly correlated with more severe overall and
      disorganization symptoms from the PANSS and BPRS, and less severe affective
      symptoms (e.g., depression, anxiety) in the overall sample. CONCLUSIONS: A three
      factor structure of the MCCB-composed of processing speed, attention/working
      memory, and learning-was replicated in a heterogeneous sample of persons with
      severe mental illness. Cognitive performance on the MCCB factors is associated
      with clinical symptoms.

PMID- 27041674
TI  - Cardiovascular autonomic neuropathy associates with nephropathy lesions in
      American Indians with type 2 diabetes.
AB  - AIMS: Cardiovascular autonomic neuropathy (CAN) predicts clinical diabetic
      nephropathy (DN). We investigated the relationship between DN structural lesions
      and CAN. METHODS: Sixty three Pima Indians with type 2 diabetes underwent kidney
      biopsies following a 6-year clinical trial testing the renoprotective efficacy of
      losartan vs. placebo. CAN was assessed a median 9.2years later. CAN variables
      included expiration/inspiration ratio (E/I), standard deviation of the normal R-R
      interval (sdNN), and low and high frequency signal power and their ratio (LF, HF,
      LF/HF); lower values reflect more severe neuropathy. Associations of CAN with
      renal structural variables were assessed by linear regression adjusted for age,
      sex, diabetes duration, blood pressure, HbA1c, glomerular filtration rate, and
      treatment assignment during the trial. RESULTS: Global glomerular sclerosis was
      negatively associated with sdNN (partial r=-0.35, p=0.01) and LF (r=-0.32,
      p=0.02); glomerular basement membrane width was negatively associated with all
      measures of CAN except for LF/HF (r=-0.28 to -0.42, p<0.05); filtration surface
      density was positively associated with sdNN, LF, and HF (r=0.31 to 0.38, p<0.05);
      and cortical interstitial fractional volume was negatively associated with HF (r=
      0.27, p=0.04). CONCLUSIONS: CAN associates with DN lesions.

PMID- 27041676
TI  - Screening of Two ADH4 Variations in a Swedish Cluster Headache Case-Control
      Material.
AB  - BACKGROUND: Cluster headache (CH) is a severe neurovascular disorder and an
      increasing amount of evidence points to a genetic contribution to this disease.
      When CH was first described, it was observed that alcohol may precipitate an
      attack during the active phase of the disease. The alcohol dehydrogenase 4 (ADH4)
      gene encodes an enzyme which contributes to the metabolization of alcohol and is,
      therefore, an interesting candidate gene for CH. Two Italian groups have reported
      association of the single nucleotide polymorphism (SNP) rs1126671 located in the
      ADH4 gene with an increased risk of CH in Italy. In addition, one of the groups
      found an association between the ADH4 SNP rs1800759 and CH. OBJECTIVE: To perform
      a replication study on the ADH4 SNPs rs1126671 and rs1800759 in a large
      homogeneous Swedish case-control cohort in order to further investigate the
      possible contribution of ADH4 to CH. METHODS: A total of 390 unrelated patients
      diagnosed with CH and 389 controls representing a general Swedish population were
      recruited to the study. DNA samples from patients and controls were genotyped for
      the two ADH4 SNPs rs1126671 and rs1800759 using quantitative real-time polymerase
      chain reaction. Statistical analyses of genotype, allele and haplotype
      frequencies for the two SNPs were performed and compared between patients and
      controls. RESULTS: For rs1126671, the minor allele frequency (A allele) was 32.8%
      (n = 254) in controls compared with 31.9% (n = 249) in CH patients. The minor
      allele frequency (A allele) of rs1800759 was 42.3% (n = 324) in controls and
      41.9% (n = 327) in CH patients. Statistical analysis showed no significant
      differences in allele as well as in genotype or haplotype frequencies between the
      patient and control group for either SNP. This was also seen after stratifying
      the patient group for experiencing alcohol as a trigger factor. CONCLUSIONS: The
      data did not support an association of the ADH4 SNPs rs1126671 and rs1800759 with
      CH. A comparison with previous studies revealed variance in genotype, allele, and
      haplotype frequencies among the different populations which might contribute to
      the contradictory results. Although a significant association with CH in Swedish
      case-control group was not found, ADH4 as a candidate gene for CH could not be
      excluded.

PMID- 27041677
TI  - An abnormal N-heterocyclic carbene based nickel complex for catalytic reduction
      of nitroarenes.
AB  - Herein we report the synthesis of a nickel(ii) dichloro complex bearing an
      abnormal N-heterocyclic carbene (aNHC). The NiCl2(aNHC)2 complex has been used as
      an efficient catalyst for the reduction of nitroarenes with hydrosilanes to give
      aromatic amines in good to excellent yields. This catalytic protocol can tolerate
      functional groups such as halides, alkenes or nitriles. Furthermore, the
      longevity of the catalyst was tested in successive catalytic cycles, which
      indicates a sustained catalytic activity over multiple catalytic cycles.

PMID- 27041678
TI  - Identification of genes associated with the astrocyte-specific gene Gfap during
      astrocyte differentiation.
AB  - Chromosomes and genes are non-randomly arranged within the mammalian cell
      nucleus, and gene clustering is of great significance in transcriptional
      regulation. However, the relevance of gene clustering and their expression during
      the differentiation of neural precursor cells (NPCs) into astrocytes remains
      unclear. We performed a genome-wide enhanced circular chromosomal conformation
      capture (e4C) to screen for genes associated with the astrocyte-specific gene
      glial fibrillary acidic protein (Gfap) during astrocyte differentiation. We
      identified 18 genes that were specifically associated with Gfap and expressed in
      NPC-derived astrocytes. Our results provide additional evidence for the
      functional significance of gene clustering in transcriptional regulation during
      NPC differentiation. 

PMID- 27041679
TI  - Kurtosis fractional anisotropy, its contrast and estimation by proxy.
AB  - The diffusion kurtosis observed with diffusion magnetic resonance imaging (dMRI)
      may vary with direction. This directional variation is summarized in the scalar
      kurtosis fractional anisotropy (KFA). Recent studies suggest that kurtosis
      anisotropy offers microstructural contrast not contained in other commonly used
      dMRI markers. We compare KFA to other dMRI contrasts in fixed rat brain and in
      human brain. We then investigate the observed contrast differences using data
      obtained in a physical phantom and simulations based on data from the phantom,
      rat spinal cord, and human brain. Lastly, we assess a strategy for rapid
      estimation of a computationally modest KFA proxy by evaluating its correlation to
      true KFA for varying number of sampling directions and signal-to-noise ratio
      (SNR) levels. We also map this proxy's b-value dependency. We find that KFA
      supplements the contrast of other dMRI metrics - particularly fractional
      anisotropy (FA) which vanishes in near orthogonal fiber arrangements where KFA
      does not. Simulations and phantom data support this interpretation. KFA therefore
      supplements FA and could be useful for evaluation of complex tissue arrangements.
      The KFA proxy is strongly correlated to true KFA when sampling is performed along
      at least nine directions and SNR is high. 

PMID- 27041680
TI  - Factors Associated with Review Board Dispositions following Re-hospitalization
      among Discharged Persons found Not Criminally Responsible.
AB  - In the Canadian forensic mental health system, a person found Not Criminally
      Responsible on account of Mental Disorder (NCRMD) and given a conditional
      discharge returns to the community while remaining under the jurisdiction of a
      provincial/territorial Review Board. However, the individual can be re
      hospitalized while on conditional discharge, for reasons such as substance use,
      violation of conditions, or violence. We investigated whether being re
      hospitalized has an impact on the factors associated with the subsequent Review
      Board disposition. Persons found NCRMD from the three largest Canadian provinces
      who were conditionally discharged at least once during the observation period
      were included in the sample (N = 1,367). These individuals were involved in 2,920
      disposition hearings; nearly one-third of patients (30%) were re-hospitalized
      after having been conditionally discharged by the Review Board. The factors
      examined included the scales of the Historical Clinical Risk Management-20 and
      salient behavior that occurred since the previous hearing, such as substance use
      or violence. The greater presence of clinical items resulted in a greater
      likelihood of a hospital detention decision at the next hearing. The effect was
      larger for the re-hospitalized group than for the group who successfully remained
      in the community since the last hearing. The results suggest that dynamic
      factors, specifically indicators of mental health, are heavily weighted by the
      Review Boards, consistent with the literature on imminent risk and in line with
      the NCRMD legislation. Copyright (c) 2016 John Wiley & Sons, Ltd. 

PMID- 27041682
TI  - Owner Evaluation of a CORA-Based Leveling Osteotomy for Treatment of Cranial
      Cruciate Ligament Injury in Dogs.
AB  - OBJECTIVE: To evaluate a center of rotation of angulation (CORA)-based leveling
      osteotomy for cranial cruciate ligament injury in dogs. STUDY DESIGN:
      Retrospective case series. ANIMALS: Dogs (n=70). METHODS: Medical records (March
      2011 to March 2012) of dogs diagnosed with a cranial cruciate ligament (CCL)
      injury treated with a CORA-based leveling osteotomy and stabilized using a bone
      plate and headless compression screw were reviewed. Radiographs were reviewed for
      tibial plateau angle and radiographic healing at final evaluation graded on a 5
      point scale. Follow-up for a minimum of 6 months postoperatively was conducted by
      owner completion of a questionnaire regarding their dog's function after surgery.
      Based on owner responses, clinical outcomes were established. RESULTS: CORA-based
      leveling osteotomy was used for 70 stifles with CCL injury. The mean time to
      final radiographic recheck was 107 days (range, 32-424 days). Radiographic
      healing scores were 42 dogs (69%) with grade 4, 17 dogs (28%) with grade 3, and 2
      dogs (3%) with grade 2. The mean time to follow-up was 11.9 months (range 6-18
      months). Fifty-four of the 70 (77%) dogs had full function, 13 (19%) had
      acceptable function, and 3 (4%) had unacceptable function. Complications occurred
      in 11 stifles (16%), including 3 incisional, 6 late-onset meniscal tears, and 2
      implant related. CONCLUSION: The described method of a CORA-based leveling
      osteotomy can be successfully performed for treatment of CCL injury in dogs. At
      the time of mid-term and long-term owner follow-up, most dogs in this case series
      had returned to full function.

PMID- 27041683
TI  - Ecological and evolutionary influences on body size and shape in the Galapagos
      marine iguana (Amblyrhynchus cristatus).
AB  - Oceanic islands are often inhabited by endemic species that have undergone
      substantial morphological evolutionary change due to processes of multiple
      colonizations from various source populations, dispersal, and local adaptation.
      Galapagos marine iguanas are an example of an island endemic exhibiting high
      morphological diversity, including substantial body size variation among
      populations and sexes, but the causes and magnitude of this variation are not
      well understood. We obtained morphological measurements from marine iguanas
      throughout their distribution range. These data were combined with genetic and
      local environmental data from each population to investigate the effects of
      evolutionary history and environmental conditions on body size and shape
      variation and sexual dimorphism. Our results indicate that body size and shape
      are highly variable among populations. Sea surface temperature and island
      perimeter, but not evolutionary history as depicted by phylogeographic patterns
      in this species, explain variation in body size among populations. Conversely,
      evolutionary history, but not environmental parameters or island size, was found
      to influence variation in body shape among populations. Finally, in all
      populations except one, we found strong sexual dimorphism in body size and shape
      in which males are larger, with higher heads than females, while females have
      longer heads than males. Differences among populations suggest that plasticity
      and/or genetic adaptation may shape body size and shape variation in marine
      iguanas. This study will help target future investigations to address the
      contribution of plasticity versus genetic adaptation on size and shape variation
      in marine iguanas.

PMID- 27041684
TI  - Viewing forests from below: fine root mass declines relative to leaf area in
      aging lodgepole pine stands.
AB  - In the continued quest to explain the decline in productivity and vigor with
      aging forest stands, the most poorly studied area relates to root system change
      in time. This paper measures the wood production, root and leaf area (and mass)
      in a chronosequence of fire-origin lodgepole pine (Pinus contorta Loudon) stands
      consisting of four age classes (12, 21, 53, and >=100 years), each replicated ~
      five times. Wood productivity was greatest in the 53-year-old stands and then
      declined in the >=100-year-old stands. Growth efficiency, the quantity of wood
      produced per unit leaf mass, steadily declined with age. Leaf mass and fine root
      mass plateaued between the 53- and >=100-year-old stands, but leaf area index
      actually increased in the older stands. An increase in the leaf area index:fine
      root area ratio supports the idea that older stand are potentially limited by
      soil resources. Other factors contributing to slower growth in older stands might
      be lower soil temperatures and increased self-shading due to the clumped nature
      of crowns. Collectively, the proportionally greater reduction in fine roots in
      older stands might be the variable that predisposes these forests to be at a
      potentially greater risk of stress-induced mortality.

PMID- 27041685
TI  - Cerebrospinal fluid biomarkers and clinical features in leucine-rich repeat
      kinase 2 (LRRK2) mutation carriers.
AB  - BACKGROUND: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the
      most common cause of inherited Parkinson's disease (PD). Nonmanifesting carriers
      of LRRK2 mutations are at high risk for developing PD. Information available on
      cerebrospinal fluid (CSF) biomarkers in LRRK2 carriers remains preliminary.
      OBJECTIVES: To measure CSF levels of alpha-synuclein, beta amyloid1-42 , total
      tau, and phospho-tau181 , in LRRK2-associated PD, idiopathic PD, nonmanifesting
      carriers, and first-degree relatives of LRRK2-associated PD patients without the
      mutation (nonmanifesting noncarriers). To correlate the clinical features and the
      integrity of the nigrostriatal pathway assessed by neuroimaging with the CSF
      biomarkers. METHODS: 138 CSF samples provided by the Michael J. Fox Foundation
      LRRK2 Cohort Consortium were analyzed: 28 LRRK2-associated PD, 35 idiopathic PD,
      41 nonmanifesting carriers, and 34 nonmanifesting noncarriers. All of the
      participants in the study were clinically assessed. Most of the participants
      underwent a dopamine transporter scan to assess the integrity of the
      nigrostriatal pathway. RESULTS: CSF levels of alpha-synuclein were similar in
      LRRK2-associated PD, nonmanifesting carriers, and nonmanifesting noncarriers but
      significantly higher than in idiopathic PD (P = .041). No differences were found
      in the concentrations of beta amyloid1-42 , total-tau, or phospho-tau181 among
      study groups. CSF alpha-synuclein levels strongly correlated with total-tau and
      phospo-tau181 levels in all groups. No significant correlation was found between
      the CSF biomarkers and the striatal binding ratios for (123)I-FP-CIT in
      nonmanifesting carriers. CONCLUSION: The CSF protein profile differs in LRRK2
      associated PD and idiopathic PD, suggesting that pathophysiological mechanisms
      different from IPD underlie LRRK2-associated PD. Cerebrospinal fluid biomarkers
      did not prove helpful in differentiating asymptomatic LRRK2 mutation carriers
      from noncarriers. (c) 2016 International Parkinson and Movement Disorder Society.

PMID- 27041686
TI  - Tolerability of 2.5% Lidocaine/Prilocaine Hydrogel in Children Undergoing
      Cryotherapy for Molluscum Contagiosum.
AB  - The tolerability of a 2.5% lidocaine/prilocaine hydrogel (Nanorap, Biolab
      Industria Farmaceutica Ltd., Sao Paulo, Brazil) was evaluated in 20 children ages
      2 to 11 years undergoing cryotherapy for molluscum contagiosum (MC). The product
      was well tolerated, with only two children presenting with eczema at the
      application site. These adverse reactions were considered unlikely to be related
      to the test product, because a patch test was negative in one of the individuals
      and the other event occurred in only one of the two treated areas. Nanorap is an
      efficacious and well-tolerated option for topical anesthesia in children
      undergoing cryotherapy for MC. 

PMID- 27041687
TI  - Hydropericardium Hepatitis Syndrome Emerged in Cherry Valley Ducks in China.
AB  - Since June 2015, a highly pathogenic disease occurred in duck flocks in China,
      causing pericardial effusion, enlarged discoloured liver, renal enlargement and
      haemorrhagic lung with a mortality ranging from 5% to 20%. Previous study
      confirmed that Fowl adenovirus group C (FAdV-C) and some field FAdVs isolates had
      been identified as causative agents of hydropericardium hepatitis syndrome (HHS)
      in chickens and geese world widely. In this study, we firstly report the
      isolation of FAdV-C from ducks with HHS. The two isolates, designated as SDSX and
      SDJX, were separated from liver samples using 9-day-old SPF chicken embryos and
      could cause severe cytopathic effects in duck and chicken embryonic kidney cells.
      The entire ORF sequences of hexon gene of the two isolates were amplified,
      sequenced and analysed by restriction fragment length polymorphism. Phylogenetic
      analysis of loop 1 sequences of hexon gene of FAdVs revealed that the two
      isolates were closely related to FAdV-C isolates, which could cause HHS in
      chickens. Experimental infection indicated that the isolate was high
      pathogenicity to 20-day-old ducks. Our study shows that the recently emerged HHS
      in ducks was caused by FAdV-C and may possess a potential risk to other poultry
      flocks.

PMID- 27041688
TI  - Cardiovascular Risk Assessment in Elderly Living Kidney Donors: Risk Comparison
      Before and After Donation Using QRISK Equation.
AB  - OBJECTIVES: This study aimed to assess whether donor age would increase the risk
      of cardiovascular comorbidities during the first few years after donation.
      Cardiovascular risk was calculated using the QRISK tool (University of Nottingham
      and EMIS, Nottingham, UK). MATERIALS AND METHODS: Data were collected from 221
      living renal transplant donors at St. George's University Hospital NHS Foundation
      Trust between 2008 and 2012 before and after donation (at 6, 12, and 24 mo).
      QRISK scores were calculated for each patient at these time points before
      stratifying our patients into 2 cohorts: cohort A (age <= 59 y) and cohort B (age
      >= 60 y). QRISK scores were then compared using unpaired t tests. RESULTS: Before
      donation, mean QRISK scores were 3.4% in cohort A and 12.4% in cohort B (P <
      .001). At 6, 12, and 24 months after kidney donation, the risks were 3.3% and
      12.2% (P < .001), 3.8% and 13.6% (P < .001), and 5% and 15.4% (P < .001) in
      cohort A versus cohort B. CONCLUSIONS: When we analyzed risk before donation,
      both age groups showed a significant increase in cardiovascular risk at 24
      months. This subtle increase in cardiovascular risk in the 2 groups may be
      attributed to changing patient demographics, such as the increasing age of
      patients, rather than the donation itself. Elderly kidney donors, therefore, are
      a key source of donation after satisfactory cardiovascular work-up. However,
      elderly kidney donors will require long-term postoperative follow-up care and
      specific counseling aimed at reducing modifiable cardiovascular risk factors.

PMID- 27041689
TI  - Metastatic neuroblastoma in infants: are survival rates excellent only within the
      stringent framework of clinical trials?
AB  - INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for
      MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to
      lack or delay of MYCN status or late registration were treated, but not included
      in the study. Our goal was to analyse survival at 10 years among the whole
      population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients'
      data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98
      infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year
      event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and
      74 %, respectively. MYCN status was significant for EFS, but not for OS in
      multivariate analysis. CONCLUSIONS: The survival rates of patients who complied
      with all the inclusion criteria for INES trials are higher compared to those that
      included also not registered patients. Five-year EFS and OS for INES 99.2 were
      87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning
      99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61
      and 68 %. MYCN amplification had a strong impact on prognosis and therefore we
      consider it unacceptable that many patients were not studied for MYCN and
      probably inadequately treated. Ten-year survival rates were shown to decrease:
      EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events,
      particularly in stage 4s. Population-based registries like European ENCCA WP 11
      task 11 will possibly clarify these data.

PMID- 27041690
TI  - Enhanced leavening properties of baker's yeast by reducing sucrase activity in
      sweet dough.
AB  - Leavening ability in sweet dough is required for the commercial applications of
      baker's yeast. This property depends on many factors, such as glycolytic
      activity, sucrase activity, and osmotolerance. This study explored the importance
      of sucrase level on the leavening ability of baker's yeast in sweet dough.
      Furthermore, the baker's yeast strains with varying sucrase activities were
      constructed by deleting SUC2, which encodes sucrase or replacing the SUC2
      promoter with the VPS8/TEF1 promoter. The results verify that the sucrase
      activity negatively affects the leavening ability of baker's yeast strains under
      high-sucrose conditions. Based on a certain level of osmotolerance, sucrase level
      plays a significant role in the fermentation performance of baker's yeast, and
      appropriate sucrase activity is an important determinant for the leavening
      property of baker's yeast in sweet dough. Therefore, modification on sucrase
      activity is an effective method for improving the leavening properties of baker's
      yeast in sweet dough. This finding provides guidance for the breeding of
      industrial baker's yeast strains for sweet dough leavening. The transformants BS1
      with deleted SUC2 genetic background provided decreased sucrase activity (a
      decrease of 39.3 %) and exhibited enhanced leavening property (an increase of
      12.4 %). Such a strain could be useful for industrial applications. 

PMID- 27041691
TI  - Thraustochytrids as production organisms for docosahexaenoic acid (DHA),
      squalene, and carotenoids.
AB  - Thraustochytrids have been applied for industrial production of the omega-3 fatty
      acid docosahexaenoic (DHA) since the 1990s. During more than 20 years of research
      on this group of marine, heterotrophic microorganisms, considerable increases in
      DHA productivities have been obtained by process and medium optimization. Strains
      of thraustochytrids also produce high levels of squalene and carotenoids, two
      other commercially interesting compounds with a rapidly growing market potential,
      but where yet few studies on process optimization have been reported.
      Thraustochytrids use two pathways for fatty acid synthesis. The saturated fatty
      acids are produced by the standard fatty acid synthesis, while DHA is synthesized
      by a polyketide synthase. However, fundamental knowledge about the relationship
      between the two pathways is still lacking. In the present review, we extract main
      findings from the high number of reports on process optimization for DHA
      production and interpret these in the light of the current knowledge of DHA
      synthesis in thraustochytrids and lipid accumulation in oleaginous microorganisms
      in general. We also summarize published reports on squalene and carotenoid
      production and review the current status on strain improvement, which has been
      hampered by the yet very few published genome sequences and the lack of tools for
      gene transfer to the organisms. As more sequences now are becoming available,
      targets for strain improvement can be identified and open for a system-level
      metabolic engineering for improved productivities. 

PMID- 27041692
TI  - Blood graft cellular composition and posttransplant outcomes in myeloma patients
      mobilized with or without low-dose cyclophosphamide: a randomized comparison.
AB  - BACKGROUND: Autologous stem cell transplantation is a standard treatment in
      multiple myeloma (MM). Blood grafts are usually collected after mobilization with
      granulocyte-colony-stimulating factor (G-CSF) alone or in a combination with
      cyclophosphamide (CY). There is limited knowledge of the possible effects of
      different mobilization regimens on blood graft characteristics and posttransplant
      outcomes. STUDY DESIGN AND METHODS: Thirty-eight patients with MM were included
      in this study. The patients were randomly assigned at registration to
      mobilization with either low-dose CY plus G-CSF (Arm A) or G-CSF alone (Arm B)
      and received three cycles of lenalidomide, bortetzomib, and dexamethasone
      induction. Flow cytometry analysis of lymphocyte subsets in the blood grafts
      after cryopreservation was performed. Hematologic and immune recovery were
      evaluated up to 12 months posttransplant. RESULTS: The blood grafts in Arm A
      contained significantly more CD34+ cells but in Arm B there was a greater
      proportion of CD34+CD38- cells and higher numbers of T and B lymphocytes as well
      as natural killer (NK) cells. The engraftment was comparable but lymphocyte count
      at 15 days posttransplant was higher in Arm B (0.8 * 10(9) /L vs. 0.5 * 10(9) /L,
      p = 0.033). At 3 and 6 months posttransplant the total number of NK cells was
      also higher in G-CSF-mobilized patients. There was no difference in progression
      free survival between the study arms. CONCLUSION: CY plus G-GSF yields more CD34+
      cells but seems to diminish lymphocyte and NK cell counts in the grafts and
      hampers immune recovery after transplantation. Thus G-CSF alone might be a
      preferred mobilization method due to more rapid immune recovery posttransplant.

PMID- 27041693
TI  - DW-MRI and (18) F-FLT PET for early assessment of response to radiation therapy
      associated with hypoxia-driven interventions. Preclinical studies using
      manipulation of oxygenation and/or dose escalation.
AB  - Early markers of treatment response may help in the management of patients by
      predicting the outcome of a specific therapeutic intervention. Here, we studied
      the potential value of diffusion-weighted MRI (DW-MRI) and (18)F-fluorothymidine
      ((18)F-FLT), markers of cell death and cell proliferation respectively, to
      predict the response to irradiation. In addition, dose escalation and/or carbogen
      breathing were used to modulate the response to irradiation. The studies were
      performed on two hypoxic rat tumor models: rhabdomyosarcoma and 9L-glioma. The
      rats were imaged using MRI and PET before and two days after the treatment. In
      both tumor models, changes in ADC (apparent diffusion coefficient) and (18)F-FLT
      SUV (standardized uptake value) were significantly correlated with the tumor
      growth delay. For both tumor models, the ADC values increased in all irradiated
      groups two days after the treatment while they decreased in the untreated groups.
      At the same time, the uptake of (18)F-FLT increased in the untreated groups and
      decreased in all treated groups. Yet, ADC values were not sensitive enough to
      predict the added value of dose escalation or carbogen breathing in either model.
      Change in (18)F-FLT uptake was able to predict the higher tumor response when
      using increased dose of irradiation, but not when using a carbogen breathing
      challenge. Our results also emphasize that the magnitude of change in (18)F-FLT
      uptake was strongly dependent on the tumor model.

PMID- 27041694
TI  - The reliability of parameters obtained by fitting of (1)H NMRD profiles and (17)O
      NMR data of potential Gd(3+)-based MRI contrast agents.
AB  - Synthetic variable temperature (1)H NMRD profiles and (17)O NMR relaxation and
      shift data were generated with a model based on the Solomon-Bloembergen-Morgan
      and Freed theories and then fitted simultaneously or individually. The effects of
      the fitting procedure and of experimental uncertainties on the resulting best-fit
      parameters were investigated. The most reliable best-fit parameters were obtained
      when all data were included in a simultaneous fitting procedure. Fitting of only
      NMRD and/or (17)O NMR data provided considerably less accurate best-fit
      parameters. Very large deviations from the values of the parameters used for the
      construction of the datasets were obtained due to the combined effects of
      uncertainties resulting from the fitting and from the data. For these fittings,
      the accuracy of the best-fit parameters appeared to be strongly dependent on the
      magnitude of synthetic parameters applied. For example, the accuracy of tauM (C)
      was low around tauM (S) = 10(-8) s. The parameters tauV and Delta(2) are strongly
      correlated in fittings of only (17)O NMR data. Consequently, only the ratio of
      these parameters can be evaluated in this way. The observations underline the
      need to reduce the number of adjustable parameters by constraining as many as
      possible of them at values obtained by independent techniques. The inaccuracies
      observed in these simulations come in addition to those caused by the inadequacy
      of the Solomon-Bloembergen-Morgan theory, particularly at low magnetic field
      strengths.

PMID- 27041695
TI  - [Care of people with dementia in a demographically changing society].

PMID- 27041696
TI  - Admission into a Nursing Home. Delay or prevention with the use of a complete
      support network?
AB  - BACKGROUND: Becoming older in Germany often leads to admission into a nursing
      home. OBJECTIVE: The aim of this study was to investigate if a complete support
      network (CSN) can contribute to preventing admission into a nursing home.
      Organizational and financial prerequisites of a CSN were documented. MATERIAL AND
      METHODS: In this study 32 patients with psychiatric disorders diagnosed according
      to the International Classification of Diseases 10 (ICD 10, 16 as F00 dementia in
      Alzheimer disease and 16 as F31-33 bipolar affective disorder, depressive episode
      and recurrent depressive disorder) were observed over a period of 2 years. The
      intervention consisted of participation in a defined CSN, which was developed by
      the Alexian Research Centre in Krefeld (ARCK). A cooperation of all persons and
      institutions involved in the care of elderly patients with psychiatric disorders
      was initiated. An individualized help plan was compiled for each patient. The
      primary outcome was admittance to a nursing home or remaining at home. The
      duration of staying at home was measured in days. User satisfaction was assessed
      with a 5-step Likert scale questionnaire. The steering process and the financial
      efforts necessary to run the CSN were descriptively evaluated. RESULTS: At the
      end of the observation period 28 out of 32 patients were not admitted to a
      nursing home. During the observational period one patient dropped out, one died
      and two were admitted to a nursing home. User satisfaction achieved a median
      score of 5 (very satisfied). No additional funding was necessary to run the CSN.
      CONCLUSION: The CSN can prevent admission to a nursing home without needing
      additional funding and the whole process can be guided by the patient.

PMID- 27041697
TI  - Difference in the Surgical Outcome of Unilateral Cleft Lip and Palate Patients
      with and without Pre-Alveolar Bone Graft Orthodontic Treatment.
AB  - Presurgical orthodontic treatment before secondary alveolar bone grafting (SABG)
      is widely performed for cleft lip/palate patients. However, no randomized
      controlled trial has been published comparing SABG outcomes in patients with, and
      without, presurgical orthodontic treatment. This randomized, prospective, single
      blinded trial was conducted between January 2012 and April 2015 to compare ABG
      volumes 6 months postoperatively between patients with and without presurgical
      orthodontic treatment. Twenty-four patients were enrolled and randomized and 22
      patients completed follow-up. Patients who had presurgical orthodontics before
      SABG had significantly improved inclination (p < 0.001) and rotation (p < 0.001)
      of the central incisor adjacent to the defect, significantly improved ABG fill
      volume (0.81 +/- 0.26 cm(3) at 6 months compared to 0.59 +/- 0.22 cm(3); p <
      0.05) and less residual alveolar bone defect (0.31 +/- 0.08 cm(3) at 6 months
      compared to s 0.55 +/- 0.14 cm(3); p < 0.001) compared to patients who did not
      have presurgical orthodontic treatment. In conclusion, orthodontic treatment
      combined with SABG results in superior bone volume when compared with
      conventional SABG alone.

PMID- 27041698
TI  - Statin use and risk of glioma: population-based case-control analysis.
AB  - Statins have been reported to decrease the incidence of cancer, but the risk of
      glioma among statin users has been investigated in only two prior observational
      studies, both of them suggesting a modest protective effect of statins. We
      conducted a matched case-control study using data from the UK-based Clinical
      Practice Research Datalink to analyse use of statins among 2469 cases with glioma
      and 24,690 controls. We performed conditional logistic regression analysis to
      calculate relative risks, estimated as odds ratios (ORs) with 95 % confidence
      intervals (CIs) adjusting for multiple confounding factors. As compared with non
      use of statins, use of statins was not associated with risk of glioma (OR for
      >=90 prescriptions=0.75; 95 % CI 0.48-1.17). Our findings do not support previous
      sparse evidence of a possible inverse association between statin use and glioma
      risk.

PMID- 27041699
TI  - The X-Ray Crystallographic Structure of the Human Neonatal Fc Receptor at Acidic
      pH Gives Insights into pH-Dependent Conformational Changes.
AB  - High levels of circulating immunoglobulin G (IgG) and serum albumin (SA) are
      maintained through recycling by the neonatal Fc receptor (FcRn). FcRn interacts
      with IgG and SA in a pHdependent manner and rescues them from lysosomal
      degradation. We have determined the crystal structure of extracellular domain of
      human FcRn, a heterodimeric complex of alpha-chain and beta2- microglobulin, at
      pH 4.5. The structure was compared with the previously reported unliganded human
      FcRn structure at pH 8.5 and complex structures of FcRn bound to SA and/or Fc
      determined at acidic pHs. Structural differences are more pronounced between the
      two unliganded FcRn structures at pH 4.5 and pH 8.5 than between unliganded FcRn
      and the complex structures at acidic pHs. At acidic pH, protonation of H166
      induces interactions with E54 and Y60 stabilizing the "WW loop" important for SA
      binding, and H161 interacts with E165 causing conformational changes of helix 3.
      These structural changes make the FcRn amenable for binding with SA at acidic pH.
      The Fc binding surface does not show any major main chain differences between the
      unliganded structures at pH 8.5 and pH 4.5. Side chain changes upon Fc binding
      were observed when compared with the complex structures. This suggests that major
      structural differences observed between unliganded and ligand bound structures
      are primarily due to pH changes rather than ligand binding. 

PMID- 27041700
TI  - Informational and Supportive Care Needs of Brain Metastases Patients and
      Caregivers: a Systematic Review.
AB  - While brain metastases (BM) are associated with significant morbidity and
      mortality, the needs of BM patients and their caregivers (CGs) remain largely
      unknown. The purpose of this systematic review was to summarize (a) the
      informational needs of BM patients and CGs, (b) their supportive care needs, and
      (c) studies evaluating existing programs and resources addressing one or more of
      informational needs. A systematic search was conducted in four databases to
      identify studies, published from 2000 to April 2015, discussing informational or
      supportive care needs of BM patients and/or their CGs. Duplicate screening, data
      abstraction, and risk of bias assessments were conducted. Results were
      qualitatively summarized. From 973 references, seven studies fulfilled inclusion
      criteria. While physical and medical informational needs concerning prognosis,
      symptom management, treatment options, and side effects were reported, no studies
      exploring patient or CG social, emotional, or spiritual informational needs were
      identified. Discordance was observed between patient, CG, and health care
      professional perspectives on patient supportive care needs. One study evaluated
      an intervention addressing informational needs. Patients required information on
      prognosis, managing symptoms, and available treatment options and associated side
      effects. They needed support managing housework, pain, and fatigue. The findings
      of this study suggest an ongoing need to elicit psychosocial informational needs,
      supportive care needs, and a need for patient- and CG-centered resource
      development. Since ascertaining these needs is vital to the delivery of patient
      centered care, efforts must be undertaken to explore these in the context of BM
      patients and CGs.

PMID- 27041701
TI  - Retrospective evaluation of toceranib phosphate (Palladia(r)) toxicity in cats.
AB  - The purpose of this study was to describe the toxicity profile of toceranib
      phosphate in tumour bearing cats. Medical records were reviewed from seven
      institutions. Patients with incomplete medical records and those receiving
      concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were
      excluded. Fifty-five cats met the inclusion criteria. Carcinoma was diagnosed in
      55% of cases. Median oral toceranib dose was 2.7 mg kg-1 and was most commonly
      administered on Monday, Wednesday and Friday. Thrombocytopenia (16.3%) and
      neutropenia (9.1%) were the most common haematologic toxicities. Azotemia (14.5%)
      and alanine aminotransferase (ALT) elevations (7.2%) were the most frequently
      encountered biochemical alterations. Gastrointestinal (GI) toxicity was seen in
      21.8% of cats, and was lower than previously reported in dogs. The results of
      this study showed that treatment of cats with toceranib is well-tolerated and
      toxicity is uncommon. Additional studies to define a more structured dosing
      schedule and to evaluate the efficacy of toceranib in the treatment of feline
      cancers are needed.

PMID- 27041702
TI  - Quantitative analysis of the BRAF V600E mutation in circulating tumor-derived DNA
      in melanoma patients using competitive allele-specific TaqMan PCR.
AB  - BACKGROUND: BRAF V600E is a common mutation in melanoma, and BRAF inhibitors are
      effective in treating of BRAF mutation-positive melanoma. DNA carrying this
      mutation is released from melanoma cells into the circulation. As such,
      circulating tumor-derived DNA (ctDNA) in peripheral blood represents a novel
      biomarker for evaluating tumor features in cancer patients. However, ctDNA is
      present in the peripheral blood at very low levels, which makes the detection of
      specific mutations in this DNA a challenge. Competitive allele-specific TaqMan
      PCR (castPCR), a straightforward commercially available assay, is a sensitive
      technique for quantitating a small amount of DNA. METHODS: The level of BRAF
      V600E ctDNA was quantified by castPCR in 26 consecutive plasma samples from six
      melanoma patients. RESULTS: The castPCR assay was performed using a mixture of
      BRAF V600E DNA and BRAF wild DNA and found to be able to detect BRAF V600E at a
      fractional abundance of >=0.5 % in 2- to 10-ng samples of genomic DNA. Cell-free
      DNA was then extracted from peripheral blood samples collected from six patients
      with melanoma harboring the BRAF V600E mutation. BRAF V600E ctDNA was detected in
      three patients, at a fractional abundance of between 1.28 and 58.0 % of total
      BRAF cell-free DNA. The abundance of BRAF V600E ctDNA correlated with tumor
      burden, as determined by computed tomography imaging. In two cases, an increase
      in the level of BRAF V600E ctDNA preceded exacerbation of clinical symptoms.
      CONCLUSION: The castPCR assay can detect and quantitate small amounts of BRAF
      V600E ctDNA in samples containing large amounts of BRAF wild cell-free DNA. Thus,
      we suggest that the castPCR assay is suitable for monitoring ctDNA in the plasma
      of melanoma patients.

PMID- 27041703
TI  - Insight into the feeding behavior of predatory mites on Beauveria bassiana, an
      arthropod pathogen.
AB  - Interactions between fungal entomopathogens and pest predators are particularly
      relevant in control of agricultural insect pests. In a laboratory study, we
      confirmed that the predatory mite, Neoseiulus barkeri, exhibited feeding behavior
      on the entomopathogenic fungus Beauveria bassiana conidia through DNA extracts.
      Using transmission electron microscopy, we determined that the majority of
      conidia found in the mite gut tended to dissolve within 24 h post ingestion,
      suggesting that the conidia had probably lost their viability. To our knowledge
      this is the first report of feeding behavior of phytoseiid mites on
      entomopathogenic fungus. The findings expand our knowledge of fungus-predator
      interactions.

PMID- 27041704
TI  - Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and
      Treatment.
AB  - Food allergy is defined as an IgE-mediated hypersensitivity response to ingested
      food with allergic symptoms ranging from urticaria to life-threatening
      anaphylaxis. Food allergy is thought to develop because of (1) failed induction
      of tolerance upon initial exposure to food antigen or (2) breakdown of
      established tolerance to food antigen. We review current understanding of the
      pathogenesis, epidemiology, and natural history of food allergy, including the
      unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal
      food allergy. We highlight emerging data on food allergy treatment and
      prevention, emphasizing the growing appeal of manipulating the gut
      microenvironment using probiotics and helminth products to blunt systemic
      allergic responses to food. 

PMID- 27041705
TI  - Patient and medication-related factors associated with hospital-acquired
      hyponatremia in patients hospitalized from heart failure.
AB  - Background Hyponatremia has been known as an important predictor of clinical
      outcomes in patients with heart failure (HF). While information on hyponatremia
      in patients with HF has been available abundantly, information on factors
      associated with increased risk of developing hospital-acquired hyponatremia (HAH)
      is still limited. Objective To identify patients and medication-related factors
      associated with HAH in patients hospitalized from HF. Setting Fatmawati Hospital
      in Jakarta, Indonesia. Methods This is a nested case-control study with patients
      developing HAH served as case group and each patient in case group was matched by
      age and gender to three patients in control group. Patients included in this
      study are patients hospitalized from HF, and coded with I.50 according to ICD-10,
      during 2011-2013 at Fatmawati Hospital in Jakarta, Indonesia. Information
      retrieved from patients' medical records included demographic profiles, vital
      signs and symptoms at admission, past medical history, medication during
      hospitalization and clinical chemistry laboratory records. Multivariable logistic
      regression analysis was performed to find out patient and treatment-related
      factors associated with the development of HAH. Main outcome measures Patients
      and medication related factors having significant association with HAH. Results
      Four hundreds sixty-four patients were included in this study and 45 of them (9.7
      %) met criteria of developing HAH so then, accordingly, 135 patients were
      selected as controls. 36 patient- and 22 treatment-related factors were analyzed
      in univariate logistic regression resulted in 20 factors having p value <0.2 and
      were included in multivariable logistic regression analysis. Final factors
      showing significant association with HAH are presence of ascites at admission
      (odds ratio = 4.7; 95 % confidence interval 1.9-11.5) and administration of
      amiodarone (3.2; 1.3-7.4) and heparin (3.1; 1.2-7.3) during hospital stay.
      Conclusion Presence of ascites at admission was found as patient-related factors
      associated with HAH in this study. In addition, administration of amiodarone and
      heparin during hospital stay were found as medication-related factors associated
      with HAH in patients hospitalized from HF. 

PMID- 27041706
TI  - A HYPOTHESIS FOR PLASTID EVOLUTION IN CHROMALVEOLATES(1).
AB  - Four eukaryotic lineages, namely, haptophytes, alveolates, cryptophytes, and
      heterokonts, contain in most cases photosynthetic and nonphotosynthetic members
      the photosynthetic ones with secondary plastids with chl c as the main
      photosynthetic pigment. These four photosynthetic lineages were grouped together
      on the basis of their pigmentation and called chromalveolates, which is usually
      understood to imply loss of plastids in the nonphotosynthetic members. Despite
      the ecological and economic importance of this group of organisms, the
      phylogenetic relationships among these algae are only partially understood, and
      the so-called chromalveolate hypothesis is very controversial. This review
      evaluates the evidence for and against this grouping and summarizes the present
      understanding of chromalveolate evolution. We also describe a testable hypothesis
      that is intended to accommodate current knowledge based on plastid and nuclear
      genomic data, discuss the implications of this model, and comment on areas that
      require further examination. 

PMID- 27041707
TI  - DISPERSAL OF HORMOSIRA BANKSII (PHAEOPHYCEAE) VIA DETACHED FRAGMENTS:
      REPRODUCTIVE VIABILITY AND LONGEVITY(1).
AB  - Drifting, fertile thalli are well documented to be the primary long-distance
      dispersal vector for many marine macroalgae, but little information about
      reproductive viability of drift is known. This study examined the reproductive
      viability and longevity of floating fragments of the intertidal Australasian
      fucoid Hormosira banksii (Turner) Decne. Beach wrack surveys and field
      experiments were conducted to test the model that long-distance dispersal is
      achieved in H. banksii via floating, fertile fronds. High densities of beach
      wrack fragments were evident during summer compared to autumn. The majority of
      beach wrack occurred on sandy beaches rather than rocky shores. Both male and
      female fragments were present in the beach wrack. Detached fronds were capable of
      releasing gametes up to 8 weeks after detachment. Beach wrack produced high
      fertilization rates and recruited successfully onto artificial panels. Results
      suggest that detached fragments are reproductively viable and that floating,
      fertile fronds may be an important mechanism for facilitating long-distance
      dispersal in this species. Nevertheless, the frequency of fronds reaching a
      suitable habitat and contributing to gene flow between populations, or colonizing
      new populations, may not be proportional to the total density of beach wrack. 

PMID- 27041708
TI  - MICROSATELLITE GENOTYPING OF SINGLE CELLS OF THE DINOFLAGELLATE SPECIES
      LINGULODINIUM POLYEDRUM (DINOPHYCEAE): A NOVEL APPROACH FOR MARINE MICROBIAL
      POPULATION GENETIC STUDIES(1).
AB  - In recent years, two new approaches have been introduced in genetic studies of
      phytoplankton species. One is the application of highly polymorphic
      microsatellite markers, which allow detailed population genetic studies; the
      other is the development of methods that enable the direct genetic
      characterization of single cells as an alternative to clonal cultures. The aim of
      this study was to combine these two approaches in a method that would allow
      microsatellite genotyping of single phytoplankton cells, providing a novel tool
      for high-resolution population genetic studies. The dinoflagellate species
      Lingulodinium polyedrum (F. Stein) J. D. Dodge was selected as a model organism
      to develop this novel approach. The method we describe here is based on several
      key developments: (i) a simple and efficient DNA extraction method for single
      cells, (ii) the characterization of microsatellite markers for L. polyedrum,
      (iii) a protocol for the species identification of single cells through the
      analysis of partial rRNA gene sequences, and (iv) a two-step multiplex PCR
      protocol for the simultaneous amplification of microsatellite markers and partial
      rRNA gene sequences from single cells. Our protocol allowed the amplification of
      up to six microsatellite loci together with either the complete ITS1-5.8S-ITS2
      region or a partial 18S region of the ribosomal gene of L. polyedrum from single
      motile cells and resting cysts. This article describes and evaluates the
      developed approach and discusses its significance for population genetic studies
      of L. polyedrum and other phytoplankton species. 

PMID- 27041709
TI  - CORRESPONDENCE BETWEEN COLD TOLERANCE AND TEMPERATE BIOGEOGRAPHY IN A WESTERN
      ATLANTIC SYMBIODINIUM (DINOPHYTA) LINEAGE(1).
AB  - Many corals form obligate symbioses with photosynthetic dinoflagellates of the
      genus Symbiodinium Freudenthal (1962). These symbionts vary genotypically, with
      their geographical distribution and abundance dependent upon host specificity and
      tolerance to temperature and light variation. Despite the importance of these
      mutualistic relationships, the physiology and ecology of Symbiodinium spp. remain
      poorly characterized. Here, we report that rDNA internal transcribed spacer
      region 2 (ITS2) defined Symbiodinium type B2 associates with the cnidarian hosts
      Astrangia poculata and Oculina arbuscula from northerly habitats of the western
      Atlantic. Using pulse-amplitude-modulated (PAM) fluorometry, we compared maximum
      photochemical efficiency of PSII of type B2 to that of common tropical
      Symbiodinium lineages (types A3, B1, and C2) under cold-stress conditions.
      Symbiont cultures were gradually cooled from 26 degrees C to 10 degrees C to
      simulate seasonal temperature declines. Cold stress decreased the maximum
      photochemical efficiency of PSII and likely the photosynthetic potential for all
      Symbiodinium clades tested. Cultures were then maintained at 10 degrees C for a 2
      week period and gradually returned to initial conditions. Subsequent to low
      temperature stress, only type B2 displayed rapid and full recovery of PSII
      photochemical efficiency, whereas other symbiont phylotypes remained
      nonfunctional. These findings indicate that the distribution and abundance of
      Symbiodinium spp., and by extension their cnidarian hosts, in temperate climates
      correspond significantly with the photosynthetic cold tolerance of these
      symbiotic algae. 

PMID- 27041710
TI  - SHORT-TERM TEMPORAL VARIABILITY OF AMMONIUM AND UREA UPTAKE BY ALEXANDRIUM
      CATENELLA (DINOPHYTA) IN CULTURES(1).
AB  - In batch cultures of four Mediterranean strains (from France, Italy, and Spain)
      of Alexandrium catenella (Whedon et Kof.) Balech growing on a daily light cycle,
      ammonium and urea uptake were estimated by the (15) N tracer technique. Ammonium
      uptake could be described by Michaelis-Menten kinetics along a substrate gradient
      of 0.1-10 MUgat N . L(-1) for the four strains, while two different patterns were
      observed for urea uptake with Michaelis-Menten kinetics for one strain and linear
      kinetics for the others. In all cases, an increase in uptake rates with time was
      noted over the daylight period. This trend led to a net increase in the maximum
      uptake rate (Vmax ; for saturable kinetics) and in the initial slope alpha. For
      ammonium, Vmax increased by a factor of 2-10 depending on the strain, and, for
      urea, the maximal uptake rates measured increased by a factor of 2-18. Temporal
      variations of half-saturation constants (Ks ) for both nutrients did not show a
      clear trend. Increases in Vmax and alpha showed an acclimation of the cells'
      uptake system over time to a N pulse, which may be explained by the light
      periodicity. For two strains, extensive ammonium release was observed during urea
      assimilation. This mechanism removes urea from the medium, so it is no longer
      available to other potential competitors, but supplies N back to the medium in
      the form of ammonium. From a methodological point of view, the phenomenon leads
      to considerable underestimates of the contribution of urea to phytoplankton
      growth. 

PMID- 27041711
TI  - BENTHIC METABOLISM ON A SHELTERED ROCKY SHORE: ROLE OF THE CANOPY IN THE CARBON
      BUDGET(1).
AB  - While the importance of canopy-forming algae in structuring ecosystems is
      recognized, their role in the carbon budget is still not well understood. To our
      knowledge, no measurements of rocky shores primary production and respiration
      under emersion periods have been carried out in situ. A benthic chamber coupled
      to a CO2 -infrared gas analyzer was used to measure gross primary production and
      respiration on the Ascophyllum nodosum (L.) Le Jol. zone of a sheltered rocky
      shore in Brittany, France. Over a year of monthly measurements on the zone with
      and without the A. nodosum canopy showed fairly high production and respiration
      values for the global community as well as carbon fluxes due to the canopy that
      largely dominated the benthic metabolism of the zone. The strong canopy
      respiration relative to the primary production also suggested a high metabolic
      activity by microscopic heterotrophs on the surface of the alga. Both the canopy
      and the understory annual primary production and respiration were under the
      control of light and temperature seasonal variations. Finally, the range of the
      amount of carbon produced on the A. nodosum zone during diurnal emersions was
      estimated. Additional measures accounting for the day-night cycles and seasonal
      light variations over an entire tidal cycle are, however, necessary to establish
      an annual carbon budget. Such measures using the benthic chamber together with
      complementary techniques would allow a better understanding of the functioning of
      sheltered rocky shores. 

PMID- 27041712
TI  - PLASTID DYNAMICS DURING SURVIVAL OF DINOPHYSIS CAUDATA WITHOUT ITS CILIATE
      PREY(1).
AB  - To survive, the marine dinoflagellate Dinophysis caudata Saville-Kent must feed
      on the plastidic ciliate Myrionecta rubra (=Mesodinium rubrum), itself a consumer
      of cryptophytes. Whether D. caudata has its own permanent chloroplasts or retains
      plastids from its ciliate prey, however, remains unresolved. Further, how long D.
      caudata plastids (or kleptoplastids) persist and remain photosynthetically active
      in the absence of prey remains unknown. We addressed those issues here, using the
      first established culture of D. caudata. Phylogenetic analyses of the plastid 16S
      rRNA and psbA gene sequences directly from the three organisms (D. caudata, M.
      rubra, and a cryptophyte) revealed that the sequences of both genes from the
      three organisms are almost identical to each other, supporting that the plastids
      of D. caudata are kleptoplastids. A 3-month starvation experiment revealed that
      D. caudata can remain photosynthetically active for ~2 months when not supplied
      with prey. D. caudata cells starved for more than 2 months continued to keep the
      plastid 16S rRNA gene but lost the photosynthesis-related genes (i.e., psaA and
      psbA genes). When the prey was available again, however, D. caudata cells starved
      for more than 2 months were able to reacquire plastids and slowly resumed
      photosynthetic activity. Taken all together, the results indicate that the nature
      of the relationship between D. caudata and its plastids is not that of permanent
      cellular acquisitions. D. caudata is an intriguing protist that would represent
      an interesting evolutionary adaptation with regard to photosynthesis as well as
      help us to better understand plastid evolution in eukaryotes. 

PMID- 27041713
TI  - DESICCATION PROTECTION AND DISRUPTION: A TRADE-OFF FOR AN INTERTIDAL MARINE
      ALGA(1).
AB  - For marine algae, the benefits of drying out are often overshadowed by the
      stresses involved. Here we used laboratory and field experiments to examine both
      the costs and benefits of desiccation in the intertidal turf alga Endocladia
      muricata (Endlichter) J. Agardh. Laboratory experiments showed that when
      Endocladia is dry, photosynthesis stops, but thermotolerance increases to the
      point that the alga is protected from heat-induced mortality. Drying rates
      measured in a wind tunnel, combined with tidal data and measured wave splash,
      indicate that a substantial fraction of the year is spent "drying out" (~30% of
      the total time available for photosynthesis). During these periods, the rate of
      drying determines how much time is spent hydrated and potentially engaged in
      photosynthesis, but also vulnerable to high temperatures. Turf algae such as
      Endocladia dry from the edge of a clump inward. Consequently, the clump center
      remains hydrated longer than the clump edge. The resulting regionalization of a
      clump results in notable patterns of frond mortality ("fairy rings," and zoned
      patterns of frond bleaching) within the Endocladia zone. 

PMID- 27041714
TI  - MODELING THE RELEASE OF DISSOLVED ORGANIC MATTER BY PHYTOPLANKTON(1).
AB  - Three models describing dissolved organic matter (DOM) flux and phytoplankton
      death, each of different levels of complexity, were constructed and tested
      against experimental data for a cyanobacterium, a chlorophyte, two diatoms, two
      dinoflagellates, and two prymnesiophytes. The simplest model described only bulk
      carbon (C) and nitrogen (N) forms of DOM (DOMC and DOMN ) and employed a fixed
      relationship between phytoplankton nutrient status and DOM release and death
      rate. The most complex model described fractions of DOM as low molecular weight
      dissolved organic carbon (DOC; saccharides, low molecular weight carbohydrates
      [DOCs]), low molecular weight nitrogenous material (comprising C and N as DOC
      associated with low molecular weight compounds containing amino acids and/or
      nucleic acids [DOCa] and N associated with DOCa [DONa], which included dissolved
      free amino acids [DFAA]), and more complex materials (DOC associated with high
      molecular weight compounds typically requiring extracellular degradation prior to
      uptake or use by microbes [DOCx] and N associated with DOCx [DONx]). It also
      employed descriptions of DOM flux and cell death related to nutrient status and
      growth rates. In all instances, material lysed from dead cells contributed to the
      DOM pool. All three models captured the gross dynamics of the primary data
      (dissolved inorganic C [DIC], dissolved inorganic N [DIN], particulate organic
      carbon [POC], particulate organic N [PON], DOC, dissolved organic N [DON]), but
      there was little or no improvement of the fit with increasing model complexity.
      However, the simplest models tended to employ excessively high growth rates to
      compensate for high fixed death rates. While the proportion of newly fixed C
      being liberated as DOMC (DOCs plus DOCa) increased as nutrient status declined,
      the actual rate of release typically did not do so and often declined. The most
      complex model gave predictions for changes in released saccharides and DFAA in
      keeping with expectations. The major obstacle to future progress is the lack of
      suitable, mass balanced data sets for further model testing. 

PMID- 27041715
TI  - ROLE OF GLUTAMATE DEHYDROGENASE AND GLUTAMINE SYNTHETASE IN CHLORELLA VULGARIS
      DURING ASSIMILATION OF AMMONIUM WHEN JOINTLY IMMOBILIZED WITH THE MICROALGAE
      GROWTH-PROMOTING BACTERIUM AZOSPIRILLUM BRASILENSE(1).
AB  - Enzymatic activities of glutamate dehydrogenase (GDH) and glutamine synthetase
      (GS) participating in the nitrogen metabolism and related ammonium absorption
      were assayed after the microalga Chlorella vulgaris Beij. was jointly immobilized
      with the microalgae-growth-promoting bacterium Azospirillum brasilense. At
      initial concentrations of 3, 6, and 10 mg . L(-1)  NH4 (+) , joint immobilization
      enhances growth of C. vulgaris but does not affect ammonium absorption capacity
      of the microalga. However, at 8 mg . L(-1)  NH4 (+) , joint immobilization
      enhanced ammonium absorption by the microalga without affecting the growth of the
      microalgal population. Correlations between absorption of ammonium per cell and
      per culture showed direct (negative and positive) linear correlations between
      these parameters and microalga populations at 3, 6, and 10 mg . L(-1)  NH4 (+) ,
      but not at 8 mg . L(-1)  NH4 (+) , where the highest absorption of ammonium
      occurred. In all cultures, immobilized and jointly immobilized, having the four
      initial ammonium concentrations, enzymatic activities of Chlorella are affected
      by A. brasilense. Regardless of the initial concentration of ammonium, GS
      activity in C. vulgaris was always higher when jointly immobilized and determined
      on a per-cell basis. When jointly immobilized, only at an initial concentration
      of 8 mg . L(-1)  NH4 (+) was GDH activity per cell higher. 

PMID- 27041716
TI  - REPRODUCTIVE ISOLATION BY SEX PHEROMONES IN THE CLOSTERIUM PERACEROSUM-STRIGOSUM
      LITTORALE COMPLEX (ZYGNEMATALES, CHAROPHYCEAE)(1).
AB  - The Closterium peracerosum-strigosum-littorale (C. psl.) complex consists of
      unicellular algae and is known to be composed of several reproductively isolated
      mating groups of heterothallic strains. Group I-E is completely isolated from
      mating groups II-A and II-B, groups II-A and II-B are partially isolated from
      each other, and only mating-type plus (mt(+) ) cells of group II-A and mating
      type minus (mt(-) ) cells of group II-B form zygotes. Based on the alignment of
      1506 group I introns, significant phylogenetic relationships were observed among
      mating groups II-A and II-B, while mating group I-E was distant from groups II-A
      and II-B. Sexual cell division in both mating-type cells of group II-A was
      stimulated in conditioned media in which cells of group II-B had been cultured.
      When mt(-) cells of group II-B were stimulated in conditioned medium derived from
      group II-A, mt(+) cells of group II-B did not respond to the conditioned medium.
      Conditioned media derived from group I-E did not exhibit sexual cell division
      (SCD)-inducing activity against any strain except those within its own group.
      From the alignment of deduced amino acid sequences from orthologous protoplast
      release-inducing protein (PR-IP) Inducer genes, we detected a significant
      similarity among groups II-A and II-B, and mating group I-E had low similarity to
      other mating groups. The existing degree of reproductive isolation can be
      partially explained by differences in molecular structures and physiological
      activities of sex pheromones of these heterothallic mating groups. 

PMID- 27041717
TI  - STATE TRANSITIONS AND NONPHOTOCHEMICAL QUENCHING DURING A NUTRIENT-INDUCED
      FLUORESCENCE TRANSIENT IN PHOSPHORUS-STARVED DUNALIELLA TERTIOLECTA(1).
AB  - Assessments of nutrient-limitation in microalgae using chl a fluorescence have
      revealed that nitrogen and phosphorus depletion can be detected as a change in
      chl a fluorescence signal when nutrient-starved algae are resupplied with the
      limiting nutrient. This photokinetic phenomenon is known as a nutrient-induced
      fluorescence transient, or NIFT. Cultures of the unicellular marine chlorophyte
      Dunaliella tertiolecta Butcher were grown under phosphate starvation to
      investigate the photophysiological mechanism behind the NIFT response. A
      combination of low temperature (77 K) fluorescence, photosynthetic inhibitors,
      and nonphotochemical quenching analyses were used to determine that the NIFT
      response is associated with changes in energy distribution between PSI and PSII
      and light-stress-induced nonphotochemical quenching (NPQ). Previous studies point
      to state transitions as the likely mechanism behind the NIFT response; however,
      our results show that state transitions are not solely responsible for this
      phenomenon. This study shows that an interaction of at least two physiological
      processes is involved in the rapid quenching of chl a fluorescence observed in P
      starved D. tertiolecta: (1) state transitions to provide the nutrient-deficient
      cell with metabolic energy for inorganic phosphate (Pi )-uptake and (2) energy
      dependent quenching to allow the nutrient-stressed cell to avoid photodamage from
      excess light energy during nutrient uptake. 

PMID- 27041718
TI  - GROWTH AND CARBON CONTENT OF THREE DIFFERENT-SIZED DIAZOTROPHIC CYANOBACTERIA
      OBSERVED IN THE SUBTROPICAL NORTH PACIFIC(1).
AB  - To develop tools for modeling diazotrophic growth in the open ocean, we
      determined the maximum growth rate and carbon content for three diazotrophic
      cyanobacteria commonly observed at Station ALOHA (A Long-term Oligotrophic
      Habitat Assessment) in the subtropical North Pacific: filamentous nonheterocyst
      forming Trichodesmium and unicellular Groups A and B. Growth-irradiance responses
      of Trichodesmium erythraeum Ehrenb. strain IMS101 and Crocosphaera watsonii J.
      Waterbury strain WH8501 were measured in the laboratory. No significant
      differences were detected between their fitted parameters (+/-CI) for maximum
      growth rate (0.51 +/- 0.09 vs. 0.49 +/- 0.17 d(-1) ), half-light saturation (73
      +/- 29 vs. 66 +/- 37 MUmol quanta . m(-2)  . s(-1) ), and photoinhibition (0 and
      0.00043 +/- 0.00087 [MUmol quanta . m(-2)  . s(-1) ](-1) ). Maximum growth rates
      and carbon contents of Trichodesmium and Crocosphaera cultures conformed to
      published allometric relationships, demonstrating that these relationships apply
      to oceanic diazotrophic microorganisms. This agreement promoted the use of
      allometric models to approximate unknown parameters of maximum growth rate (0.77
      d(-1) ) and carbon content (480 fg C . MUm(-3) ) for the uncultivated,
      unicellular Group A cyanobacteria. The size of Group A was characterized from
      samples from the North Pacific Ocean using fluorescence-activated cell sorting
      and real-time quantitative PCR techniques. Knowledge of growth and carbon content
      properties of these organisms facilitates the incorporation of different types of
      cyanobacteria in modeling efforts aimed at assessing the relative importance of
      filamentous and unicellular diazotrophs to carbon and nitrogen cycling in the
      open ocean. 

PMID- 27041719
TI  - OCCURRENCE AND CHARACTERIZATION OF ARABINOGALACTAN-LIKE PROTEINS AND
      HEMICELLULOSES IN MICRASTERIAS (STREPTOPHYTA)(1).
AB  - The cell wall of the green alga Micrasterias denticulata Breb. ex Ralfs
      (Desmidiaceae, Zygnematophyceae, Streptophyta) was investigated to obtain
      information on the composition of component polysaccharides and proteoglycans to
      allow comparison with higher plants and to understand cell wall functions during
      development. Various epitopes currently assigned to arabinogalactan-proteins
      (AGPs) of higher plants could be detected in Micrasterias by immuno TEM and
      immunofluorescence methods, but the walls did not bind the beta-d-glycosyl-Yariv
      (beta-GlcY) reagent. Secretory vesicles and the primary wall were labeled by
      antibodies against AGPs (JIM8, JIM13, JIM14). Dot and Western blot experiments
      indicated a proteoglycan nature of the epitopes recognized, which consisted of
      galactose and xylose as major sugars by high performance anion exchange
      chromatography with pulsed amperometric detection (HPAEC-PAD). Epitopes of alkali
      soluble polysaccharides assigned to noncellulosic polysaccharides in higher
      plants could be detected and located in the wall during its formation. The
      polyclonal anti-xyloglucan (anti-XG) antibody labeled primary and secondary wall
      of Micrasterias, whereas the monoclonal antibody CCRC-M1, directed against the
      fucose/galactose side chain of xyloglucan (XyG), did not recognize any
      structures. Labeling by anti-XG antibody at the trans-sites of the dictyosomes
      and at wall material containing vesicles indicated that secretion of the epitopes
      occurred similar to higher plants. The presence of (1->3, 1->4)-beta-glucan
      (mixed linked glucan) in the secondary cell wall but not in the primary cell wall
      of Micrasterias could be demonstrated by an antibody recognizing this glucan
      type, whereas (1->3)-beta-glucan (callose) could not be detected. The analytical
      results revealed that alkali-soluble polysaccharides in the secondary wall of
      Micrasterias consist mostly of (1->3, 1->4)-beta-d-glucan. 

PMID- 27041720
TI  - UNDERSTANDING NITROGEN LIMITATION IN AUREOCOCCUS ANOPHAGEFFERENS (PELAGOPHYCEAE)
      THROUGH cDNA AND qRT-PCR ANALYSIS(1).
AB  - Brown tides of the marine pelagophyte Aureococcus anophagefferens Hargraves et
      Sieburth have been investigated extensively for the past two decades. Its growth
      is fueled by a variety of nitrogen (N) compounds, with dissolved organic nitrogen
      (DON) being particularly important during blooms. Characterization of a cDNA
      library suggests that A. anophagefferens can assimilate eight different forms of
      N. Expression of genes related to the sensing, uptake, and assimilation of
      inorganic and organic N, as well as the catabolic process of autophagy, was
      assayed in cells grown on different N sources and in N-limited cells. Growth on
      nitrate elicited an increase in the relative expression of nitrate and ammonium
      transporters, a nutrient stress-induced transporter, and a sensory kinase. Growth
      on urea increased the relative expression of a urea and a formate/nitrite
      transporter, while growth on ammonium resulted in an increase in the relative
      expression of an ammonium transporter, a novel ATP-binding cassette (ABC)
      transporter and a putative high-affinity phosphate transporter. N limitation
      resulted in a 30- to 110-fold increase in the relative expression of nitrate,
      ammonium, urea, amino acid/polyamine, and formate/nitrite transporters. A.
      anophagefferens demonstrated the highest relative accumulation of a transcript
      encoding a novel purine transporter, which was highly expressed across all N
      sources. This finding suggests that purines are an important source of N for the
      growth of this organism and could possibly contribute to the initiation and
      maintenance of blooms in the natural environment. 

PMID- 27041721
TI  - EXPRESSION PROFILING OF THE MANNURONAN C5-EPIMERASE MULTIGENIC FAMILY IN THE
      BROWN ALGA LAMINARIA DIGITATA (PHAEOPHYCEAE) UNDER BIOTIC STRESS CONDITIONS(1).
AB  - The aim of this study was to profile expression of mannuronan C5-epimerase (ManC5
      E) genes of Laminaria digitata (Huds.) J. V. Lamour. under treatment with brown
      alga cell wall components known to induce defense reaction in this organism.
      After determining that incubation in the presence of homo-guluronates increased
      the accumulation of ManC5-E transcripts, we cloned a number of partial ManC5-E
      genes from nonelicited and elicited specimens. In addition to these fragments,
      previously identified genes from sporophyte and protoplast cDNA libraries were
      considered for a clustering analysis. Several groups of ManC5-E genes were
      observed, including groups containing sequences specific from nonelicited and
      elicited sporophytes, and sequences isolated from protoplasts. Quantitative real
      time PCR experiments were then carried out using genes representative of
      different groups. Results of transcript accumulation during protoplast
      regeneration and sporophyte elicitation supported the hypothesis that specific C5
      epimerase genes are recruited under pathogen attack, enabling L. digitata to
      modify its cell wall in response to environmental stimuli. 

PMID- 27041722
TI  - CELL WALL CARBOHYDRATE EPITOPES IN THE GREEN ALGA OEDOGONIUM BHARUCHAE F. MINOR
      (OEDOGONIALES, CHLOROPHYTA)(1).
AB  - Cell wall changes in vegetative and suffultory cells (SCs) and in oogonial
      structures from Oedogonium bharuchae N. D. Kamat f. minor Velez were
      characterized using monoclonal antibodies against several carbohydrate epitopes.
      Vegetative cells and SCs develop only a primary cell wall (PCW), whereas mature
      oogonial cells secrete a second wall, the oogonium cell wall (OCW). Based on
      histochemical and immunolabeling results, (1->4)-beta-glucans in the form of
      crystalline cellulose together with a variable degree of Me-esterified
      homogalacturonans (HGs) and hydroxyproline-rich glycoprotein (HRGP) epitopes were
      detected in the PCW. The OCW showed arabinosides of the extensin type and low
      levels of arabinogalactan-protein (AGP) glycans but lacked cellulose, at least in
      its crystalline form. Surprisingly, strong colabeling in the cytoplasm of mature
      oogonia cells with three different antibodies (LM-5, LM-6, and CCRC-M2) was
      found, suggesting the presence of rhamnogalacturonan I (RG-I)-like structures.
      Our results are discussed relating the possible functions of these cell wall
      epitopes with polysaccharides and O-glycoproteins during oogonium
      differentiation. This study represents the first attempt to characterize these
      two types of cell walls in O. bharuchae, comparing their similarities and
      differences with those from other green algae and land plants. This work
      represents a contribution to the understanding of how cell walls have evolved
      from simple few-celled to complex multicelled organisms. 

PMID- 27041723
TI  - EARLY DEVELOPMENT PATTERN OF THE BROWN ALGA ECTOCARPUS SILICULOSUS (ECTOCARPALES,
      PHAEOPHYCEAE) SPOROPHYTE(1).
AB  - The distant phylogenetic position of brown macroalgae from the other
      multicellular phyla offers the opportunity to study novel and alternative
      developmental processes involved in the establishment of multicellularity. At
      present, however, very little information is available about developmental
      patterning in this group. Ectocarpus siliculosus (Dillwyn) Lyngb. has uniseriate
      filaments and displays one of the simplest architectures in the Phaeophyceae. The
      aim of this study was to decipher the morphogenetic steps that lead to the
      development of the Ectocarpus sporophyte. We carried out a detailed morphometric
      study of the events that occurred between gamete germination and the 100-cell
      stage. This analysis was performed on two ecologically distant isolates to assess
      plasticity in developmental patterning within this species. Cell sizes were
      measured in both isolates, allowing the definition of two main cell types based
      on their shape (round and elongated). On average, the filament is composed of
      about 40% round cells, which are present in the central region of the filament,
      but different combinations of the two cell types within filaments were observed
      and quantified. Young sporophytes grew apically, with elongated cells
      progressively differentiating into round cells. Secondary filaments emerged
      preferentially on round cells, primarily from the older central cells.
      Statistical analyses showed that the pattern of branching was regulated to ensure
      a stereotyped architecture. This description of the developmental patterning
      during the growth of the E. siliculosus sporophyte will serve as a base for more
      detailed studies of development, in this species and in brown algae in general. 

PMID- 27041724
TI  - LOCALIZATION OF OXYTETRACYCLINE IN CHLAMYDOMONAS REINHARDTII (CHLOROPHYCEAE)(1).
AB  - Oxytetracycline (OTC) is an important antimicrobial used in aquaculture. However,
      residues of OTC have been isolated from nontarget aquatic organisms, sediments,
      and water located near aquaculture facilities. Identifying OTC in plant material
      is particularly difficult due to interference from pigments and polyphenol
      substances but is important especially for algae since they are a primary food
      source for fish in early life stages. In this study, we describe the effect of
      OTC (0.1, 1, 10, 25, 50, 100 MUg . mL(-1) ) on cell growth, and the localization
      of OTC (0, 1, 25, 100 MUg . mL(-1) ) in vacuoles of Chlamydomonas reinhardtii P.
      A. Dang. (wildtype, ATCC 18798). We also present a method for semiquantifying OTC
      in living cells using fluorescent microscopy and Adobe Photoshop. We exposed
      algal cells to OTC and sampled after 2 or 7 d exposure. On day 7, OTC
      significantly inhibited algal growth at 1, 10, 25, 50, and 100 MUg . mL(-1) .
      When viewed with fluorescent microscopy, cells exposed to the 25 and 100 MUg .
      mL(-1) contained yellow fluorescent areas, <=1 MUm in diameter that were easily
      discernable against the red fluorescence of the intracellular chl. The
      fluorescent areas corresponded to small spherical vacuoles (i.e., polyphosphate
      bodies that contain calcium and magnesium complexed with polyphosphate) seen in
      the cells by LM. Since OTC has a high affinity for divalent cations, we suggest
      that OTC is localized in these vacuoles. 

PMID- 27041725
TI  - ASYMMETRY OF EYESPOT AND MATING STRUCTURE POSITIONS IN ULVA COMPRESSA (ULVALES,
      CHLOROPHYTA) REVEALED BY A NEW FIELD EMISSION SCANNING ELECTRON MICROSCOPY
      METHOD(1).
AB  - Gametes of the marine green alga Ulva compressa L. are biflagellate and pear
      shaped, with one eyespot at the posterior end of the cell. The species is at an
      early evolutionary stage between isogamy and anisogamy. In the past, zygote
      formation of green algae was categorized solely by the relative sizes of gametes
      produced by two mating types (+ and -). Recently, however, locations of cell
      fusion sites and/or mating structures of gametes have been observed to differ
      between mating types in several green algae (asymmetry of cell fusion site and/or
      mating structure positions). To use this asymmetry for determining gamete mating
      type, we explored a new method, field emission scanning electron microscopy (FE
      SEM), for visualizing the mating structure of U. compressa. When gametes were
      subjected to drying stress in the process of a conventional critical-point-drying
      method, a round structure was observed on the cell surfaces. In the mating type
      MGEC-1 (mt(+) ), this structure was located on the same side of the cell as the
      eyespot, whereas it was on the side opposite the eyespot in the mating type MGEC
      2 (mt(-) ). The gametes fuse at the round structures. TEM showed an alignment of
      vesicles inside the cytoplasm directly below the round structures, which are
      indeed the mating structures. Serial sectioning and three-dimensional
      construction of TEM micrographs confirmed the association of the mating structure
      with flagellar roots. The mating structure was associated with 1d root in the
      MGEC-1 gamete but with 2d root in the MGEC-2 gamete. 

PMID- 27041726
TI  - CRYPTIC DIVERSITY AND PHYLOGENETIC RELATIONSHIPS WITHIN THE MASTOCARPUS
      PAPILLATUS SPECIES COMPLEX (RHODOPHYTA, PHYLLOPHORACEAE)(1).
AB  - Mastocarpus papillatus (C. Agardh) Kutz. is a common intertidal red alga
      occurring along the west coast of North America from Baja California to Alaska.
      Sequencing of both the chloroplast-encoded rbcL gene and the nuclear ribosomal
      internal transcribed spacer (ITS) regions of ~200 specimens from California to
      Alaska revealed that M. papillatus is actually a complex of at least five
      species. All five species have high bootstrap support in phylogenetic analyses of
      both genetic regions, and in the case of the ITS marker, the species also have
      distinctive patterns of indels. Three of the species are localized in the mid- to
      upper intertidal, whereas two of the species occur in the low intertidal. The
      species also have different geographic ranges that overlap in the Vancouver
      Island area of British Columbia. No distinctive, reliable morphological
      differences were observed among the species. Although a variety of names are
      available for species in the complex, it is not yet clear which name goes with
      which species. As part of the survey, I also sequenced other species of
      Mastocarpus in the northeast Pacific region, and I provide new distribution
      records for M. jardinii ( J. Agardh) J. A. West and for a nonpapillate and
      probably undescribed species of Mastocarpus. 

PMID- 27041727
TI  - SALT-INDUCED ALTERATIONS IN LIPID COMPOSITION OF DIATOM NITZSCHIA LAEVIS
      (BACILLARIOPHYCEAE) UNDER HETEROTROPHIC CULTURE CONDITION(1).
AB  - The diatom Nitzschia laevis Hust. is a potential producer of eicosapentaenoic
      acid (EPA). To elucidate its cellular response to salt stress, the effects of
      salinity on EPA production, lipid composition, and fatty acid distribution in the
      lipid pool were investigated. The highest contents of total fatty acids, EPA, and
      polar lipids were all obtained at NaCl of 20 g . L(-1) , under which 71.3% of
      total EPA existed in polar lipid fractions. In N. laevis, high salt concentration
      might induce the decrease in neutral lipids (NLs), whereas the production of
      polar lipids, including phospholipids (PLs) and glycolipids (GLs), was enhanced.
      The degree of fatty acid unsaturation of both neutral and polar lipid fractions
      increased sharply when NaCl concentration increased from 10 to 20 g . L(-1) but
      decreased at NaCl concentration of 30 g . L(-1) . The amount of total free
      sterols was increased with the increase in salt concentration. All these changes
      in lipid and fatty acids suggested a decrease in membrane permeability and
      fluidity under high salt concentration, which could help the alga acclimate to
      the salinity stress. 

PMID- 27041728
TI  - TWO-DIMENSIONAL GEL ELECTROPHORESIS ANALYSIS OF BROWN ALGAL PROTEIN EXTRACTS(1).
AB  - High-quality protein extracts are required for proteomic studies, a field that is
      poorly developed for marine macroalgae. A reliable phenol extraction protocol
      using Scytosiphon gracilis Kogame and Ectocarpus siliculosus (Dillwyn) Lyngb.
      (Phaeophyceae) as algal models resulted in high-quality protein extracts. The
      performance of the new protocol was tested against four methods available for
      vascular plants and a seaweed. The protocol, which includes an initial step to
      remove salts from the algal tissues, allowed the use of highly resolving two
      dimensional gel electrophoresis (2-DE) protein analyses, providing the
      opportunity to unravel potentially novel physiological processes unique to this
      group of marine organisms. 

PMID- 27041729
TI  - A NOVEL EPIPHYTIC CYANOBACTERIAL SPECIES FROM THE GENUS BRASILONEMA CAUSING
      DAMAGE TO EUCALYPTUS LEAVES(1).
AB  - A cyanobacterial mat colonizing the leaves of Eucalyptus grandis was determined
      to be responsible for serious damage affecting the growth and development of
      whole plants under the clonal hybrid nursery conditions. The dominant
      cyanobacterial species was isolated in BG-11 medium lacking a source of combined
      nitrogen and identified by cell morphology characters and molecular phylogenetic
      analysis (16S rRNA gene and cpcBA-IGS sequences). The isolated strain represents
      a novel species of the genus Brasilonema and is designated Brasilonema
      octagenarum strain UFV-E1. Thin sections of E. grandis leaves analyzed by light
      and electron microscopy showed that the B. octagenarum UFV-E1 filaments penetrate
      into the leaf mesophyll. The depth of infection and the mechanism by which the
      cyanobacterium invades leaf tissue were not determined. A major consequence of
      colonization by this cyanobacterium is a reduction in photosynthesis in the host
      since the cyanobacterial mats decrease the amount of light incident on leaf
      surfaces. Moreover, the cyanobacteria also interfere with stomatal gas exchange,
      decreasing CO2 assimilation. To our knowledge, this is the first report of an
      epiphytic cyanobacterial species causing damage to E. grandis leaves. 

PMID- 27041730
TI  - INTERCOLONIAL VARIABILITY IN MACROMOLECULAR COMPOSITION IN P-STARVED AND P
      REPLETE SCENEDESMUS POPULATIONS REVEALED BY INFRARED MICROSPECTROSCOPY(1).
AB  - Macromolecular variability in microalgal populations subject to different
      nutrient environments was investigated, using the chlorophyte alga Scenedesmus
      quadricauda (Turpin) Breb. as a model organism. The large size of the four-cell
      coenobia in the strain used in this study (~35 MUm diameter) conveniently allowed
      high quality spectra to be obtained from individual coenobia using a laboratory
      based Fourier transform infrared (FTIR) microscope with a conventional globar
      source of IR. By drawing sizable subpopulations of coenobia from two Scenedesmus
      cultures grown under either nutrient-replete or P-starved conditions, the
      population variability in macromolecular composition, and the effects of nutrient
      change upon this, could be estimated. On average, P-starved coenobia had higher
      carbohydrate and lower protein absorbance compared with P-replete coenobia. These
      parameters varied between coenobia with histograms of the ratio of absorbance of
      the largest protein and carbohydrate bands being Gaussian distributed.
      Distributions for the P-replete and P-starved subpopulations were nonoverlapping,
      with the difference in mean ratios for the two populations being statistically
      significant. Greater variance was observed in the P-starved subpopulation. In
      addition, multivariate models were developed using the spectral data, which could
      accurately predict the nutrient status of an independent individual coenobium,
      based on its FTIR spectrum. Partial least squares discriminant analysis (PLS-DA)
      was a better prediction method compared with soft independent modeling by class
      analogy (SIMCA). 

PMID- 27041731
TI  - MOLECULAR EVIDENCE CONFIRMS SISTER RELATIONSHIP OF ARDISSONEA, CLIMACOSPHENIA,
      AND TOXARIUM WITHIN THE BIPOLAR CENTRIC DIATOMS (BACILLARIOPHYTA, MEDIOPHYCEAE),
      AND CLADISTIC ANALYSES CONFIRM THAT EXTREMELY ELONGATED SHAPE HAS ARISEN TWICE IN
      THE DIATOMS(1).
AB  - With the use of a new kit from Qiagen to amplify total genome quantity, DNA was
      bulked up from two diatoms that are difficult to grow (Ardissonea and
      Climacosphenia), and the nuclear SSU rRNA gene was successfully amplified.
      Results of Bayesian analyses showed that these diatoms are sister to Toxarium and
      belong to the bi- and multipolar centric diatoms. The results indicate that
      extremely elongate shape has arisen at least twice in diatoms, in the true
      pennates, and in the bipolar centrics. The two lateral pattern centers of
      Ardissonea and Climacosphenia likely represent a modified annulus that subtends
      ribs internally as well as externally. Studies of sexual reproduction are needed
      to determine whether Ardissonea, Climacosphenia, and Toxarium achieve their
      elongate shape by similar means to each other and to true pennates, that is, by
      controlling the expansion of the auxospores by sequential addition of silicified
      bands (to form a properizonium or perizonium). 

PMID- 27041732
TI  - DETECTION OF DIATOM XANTHOPHYLL CYCLE USING SPECTRAL REFLECTANCE(1).
AB  - Analysis of reflectance spectra was used to monitor the conversion of
      diadinoxanthin (DD) into diatoxanthin (DT) in two benthic diatom species, Amphora
      coffeaeformis (C. Agardh) Kutz. and Cylindrotheca closterium (Ehrenb.) J. C.
      Lewin et Reiman, cultured at high light (HL, 400 MUmol . m(-2)  . s(-1) PAR) and
      low light (LL, 25 MUmol . m(-2)  . s(-1) PAR). Cultures were exposed to
      saturating light for 32 min. HL cultures of both species showed higher (DT + DD)
      content, whereas LL cultures exhibited higher chl a and fucoxanthin content. DD
      to DT conversion, measured by HPLC, occurred mainly in the first 2 min (LL) or 5
      min (HL) after exposure to saturating light. Nonphotochemical quenching (NPQ),
      measured by PAM fluorescence, showed the same pattern as DT/(DD + DT), resulting
      in a linear relationship between these parameters. Addition of dithiothreitol
      (DTT) blocked the conversion of DD into DT and significantly reduced NPQ
      induction. Reflectance spectra showed no obvious change after light exposure.
      However, second derivative spectra (deltadelta) showed a shift in reflectance
      from 487 to 508 nm, which was not present for DTT-treated samples. Changes in
      deltadelta487 were strongly correlated with changes in DD (r = 0.76), while
      changes in deltadelta508 were strongly correlated with changes in DT (r = 0.94).
      The best index to estimate DD to DT conversion was deltadelta508 /deltadelta630
      (r = 0.87). This index was very sensitive to minute changes that occurred
      immediately after exposure to light and was species insensitive. Good
      relationships were observed between indices for xanthophyll cycle activation (DD
      to DT conversion and NPQ induction) and the second derivative spectra. With
      further in situ validation, this index may prove to be highly useful for
      investigation into aquatic global photoregulation mechanisms in diatom-dominated
      samples. 

PMID- 27041733
TI  - Prophylactic pasireotide administration following pancreatic resection reduces
      cost while improving outcomes.
AB  - BACKGROUND AND OBJECTIVES: Pasireotide decreases leak rates after pancreatic
      resection, though significant drug cost may be prohibitive. We conducted a cost
      effectiveness analysis to determine whether prophylactic pasireotide possesses a
      reasonable cost profile. METHODS: A cost-effectiveness model compared pasireotide
      administration after pancreatic resection versus usual care, populated by
      probabilities of clinical outcomes from a randomized trial and hospital costs
      (2013 US$) from a university pancreatic disease center. Sensitivity analyses were
      performed to identify influential clinical components of the model. RESULTS: With
      the cost of pasireotide included, per patient costs of pancreatectomy, including
      those for readmission, were lower in the intervention arm (41,769 versus 42,159$;
      net savings of 390$, or 1%). This was associated with a 56% reduction in
      pancreatic fistula/pancreatic leak/abscess (PF/PL/A; 21.9-9.2%). Pasireotide cost
      would need to increase by over 15.4% to make the intervention strategy more
      costly than usual care. Sensitivity analyses exploring variability of key model
      inputs demonstrated that the three strongest drivers of cost were (i) cost of
      pasireotide; (ii) probability of readmission; and (iii) probability of PF/PL/A.
      CONCLUSIONS: Prophylactic pasireotide administration following pancreatectomy is
      cost savings, reducing expensive post-operative sequealae (major complications
      and readmissions). Pasireotide should be utilized as a cost-saving measure in
      pancreatic resection. J. Surg. Oncol. 2016;113:784-788. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27041734
TI  - Analysis of the BRAFV600E mutation in 19 cases of Langerhans cell histiocytosis
      in Japan.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal
      proliferation of CD1a- and CD207 (langerin)-positive dendritic cells. Mutated
      BRAF (p.V600E) is observed in histiocyte-related diseases and dendritic cell
      related diseases, including LCH. BRAFV600E is observed in some LCH cases and is
      thought to be involved in maintaining MAPK activation. We retrospectively
      analyzed BRAFV600E in 19 patients diagnosed with LCH. In our study, direct
      sequencing for exon 15, a mutation hotspot, demonstrated that 4 out of the 19
      patients (21%) harbored a GTG > GAG (valine > glutamic acid) base substitution,
      which encodes BRAFV600E. The clinical impact of BRAFV600E in such diseases is
      unclear. The frequency of BRAFV600E in our LCH patients from Japan was lower than
      that reported in the United States and in Germany. However, reports from Asia
      tend to show a lower rate of the BRAFV600E mutation. These results imply the
      possibility of different genetic backgrounds in the pathogenesis of LCH across
      various ethnicities. We also performed an immunohistochemical analysis to detect
      BRAFV600E using the mutation-specific monoclonal antibody. However,
      immunohistochemical analysis failed to detect any mutated protein in any of the 4
      BRAFV600E-positive cases. This implies that at present, BRAFV600E should be
      assessed by direct sequencing. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27041735
TI  - Protein phosphatase 4 plays dual roles during cell proliferation.
AB  - OBJECTIVES: Protein phosphatase 4 (PP4) has been reported to be indispensable for
      cell proliferation and survival. Deletion of PP4 has been shown to induce
      abnormal and even lethal events in growth and development both in lower
      eukaryotes and in mammals. However, until now, effects of PP4 up-regulation have
      remained unclear. MATERIALS AND METHODS: To test effects of PP4 on cell
      proliferation, cell cycle and morphology in HepG2 cells, it was down-regulated
      using PP4 siRNA or its activity was inhibited using PP4RL (a PP4 phosphatase-dead
      mutant) adenoviruses. Alternatively, PP4 was up-regulated using PP4 adenoviruses.
      Next, we used a functional proteomic approach to identify proteins that may
      interact with PP4. Furthermore, we performed rescue experiments to verify the
      possible mechanisms. RESULTS: To our surprise, we found that both up-regulation
      and inhibition of PP4 inhibited cell proliferation. Unlike PP4 inhibition, PP4 up
      regulation induced prominent arrest at the prometaphase/metaphase transition by
      causing defects in chromosome alignment and spindle assembly. Moreover, we
      identified scaffold attachment factor A (SAF-A) (an important protein required
      for kinetochore-microtubule attachment that participates in the
      prometaphase/metaphase transition), to be a novel protein that interacts with
      PP4, using a proteomic approach. Thus, mutual regulatory mechanisms exist between
      PP4 and SAF-A. Interactions between PP4 and SAF-A played a role in
      prometaphase/metaphase transition. CONCLUSIONS: Our data demonstrate a novel
      regulatory mechanism involving PP4 in cell proliferation.

PMID- 27041736
TI  - Higher expression of EpCAM is associated with poor clinical and pathological
      responses in breast cancer patients undergoing neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy (NAC) is a standard regimen in treatment of breast
      cancer patients, but some are resistant to NAC. We hypothesized that breast
      cancer cells overexpressing epithelial cell adhesion molecule (EpCAM) could be
      resistant to NAC, contributing to a poor prognosis. Seventy patients with breast
      cancer were treated with NAC. Core needle biopsy (CNB) specimens and resected
      tumors before and after NAC, respectively, were examined for expression of EpCAM.
      In resected tumors, high EpCAM expression correlated with lymphovascular invasion
      status and nuclear grade (P = 0.01 and 0.008, respectively), and was associated
      with poor pathological and clinical responses (P < 0.001). High tumoral EpCAM
      expression in resected tumor was independently related to a poor pathological
      response. Patients with high EpCAM expression before and after NAC (high-to-high
      group) showed worse pathological and clinical responses (P = 0.008 and <0.001,
      respectively) than the patients with high and low EpCAM expression before and
      after NAC, respectively (high-to-low group). The overall survival rate of the
      high-to-high group appeared shorter compared with the high-to low-group (P =
      0.049). Our findings imply that higher levels of EpCAM in breast cancer may be
      associated with poor response to NAC via a potential chemoresistant effect. 

PMID- 27041737
TI  - Evidence for ice-free summers in the late Miocene central Arctic Ocean.
AB  - Although the permanently to seasonally ice-covered Arctic Ocean is a unique and
      sensitive component in the Earth's climate system, the knowledge of its long-term
      climate history remains very limited due to the restricted number of pre
      Quaternary sedimentary records. During Polarstern Expedition PS87/2014, we
      discovered multiple submarine landslides along Lomonosov Ridge. Removal of
      younger sediments from steep headwalls has led to exhumation of Miocene sediments
      close to the seafloor. Here we document the presence of IP25 as a proxy for
      spring sea-ice cover and alkenone-based summer sea-surface temperatures >4 
      degrees C that support a seasonal sea-ice cover with an ice-free summer season
      being predominant during the late Miocene in the central Arctic Ocean. A
      comparison of our proxy data with Miocene climate simulations seems to favour
      either relatively high late Miocene atmospheric CO2 concentrations and/or a weak
      sensitivity of the model to simulate the magnitude of high-latitude warming in a
      warmer than modern climate. 

PMID- 27041739
TI  - Some pitfalls in application of functional data analysis approach to association
      studies.
AB  - One of the most effective methods for gene-based mapping employs functional data
      analysis, which smoothes data using standard basis functions. The full functional
      linear model includes a functional representation of genotypes and their effects,
      while the beta-smooth only model smoothes the genotype effects only. Benefits and
      limitations of the beta-smooth only model should be studied before using it in
      practice. Here we analytically compare the full and beta-smooth only models under
      various scenarios. We show that when the full model employs two sets of basis
      functions equal in type and number, genotypes smoothing is eliminated from the
      model and it becomes analytically equivalent to the beta-smooth only model. If
      the basis functions differ only in type, genotypes smoothing is also eliminated
      from the full model, but the type of basis functions used for smoothing genotype
      effects becomes redefined. This leads to misinterpretation of the results and may
      reduce statistical power. When basis functions differ in number, no analytical
      comparison of the full and beta-smooth only models is possible. However, we show
      that the numbers of basis functions set unequal can become equal during the
      analysis, and the full model becomes disadvantageous. 

PMID- 27041738
TI  - Immediate ecotoxicological effects of short-lived oil spills on marine biota.
AB  - Marine environments are frequently exposed to oil spills as a result of
      transportation, oil drilling or fuel usage. Whereas large oil spills and their
      effects have been widely documented, more common and recurrent small spills
      typically escape attention. To fill this important gap in the assessment of oil
      spill effects, we performed two independent supervised full sea releases of 5
      m(3) of crude oil, complemented by on-board mesocosm studies and sampling of
      accidentally encountered slicks. Using rapid on-board biological assays, we
      detect high bioavailability and toxicity of dissolved and dispersed oil within 24
      h after the spills, occurring fairly deep (8 m) below the slicks. Selective
      decline of marine plankton is observed, equally relevant for early stages of
      larger spills. Our results demonstrate that, contrary to common thinking, even
      small spills have immediate adverse biological effects and their recurrent nature
      is likely to affect marine ecosystem functioning. 

PMID- 27041740
TI  - When Parents Know Little about What Happened: Parent-guided Conversations,
      Stress, and Young Children's Eyewitness Memory.
AB  - This study examined how 4- to 7-year-olds' memories for a stressor were
      influenced by conversations with a parent who had little knowledge of the target
      event, and the stress children experienced before, during, and after the event.
      Children (N = 43) watched a mildly stressful video before talking about it with a
      parent. Parents were asked to focus on either the children's feelings or the
      content of the video itself. A researcher interviewed the children about their
      memory following the conversation. Behavioral and physiological measures of
      children's stress were collected at multiple stages. Children recalled more
      inaccurate information with the parent than with the interviewer. Younger age and
      parent insecure attachment were associated with poorer memory. Manipulation of
      parents' emotion orientation did not predict memory, but individual differences
      in the talk did, although in different ways from what would be expected from
      research on conversations about shared events. Less stress (according to self
      reported happiness and observed negative affect) before and after, but not
      during, the stressor was linked with better memory. Implications for children's
      memory in legal settings are discussed. Copyright (c) 2016 John Wiley & Sons,
      Ltd. 

PMID- 27041741
TI  - Scrambler Therapy for the management of chronic pain.
AB  - PURPOSE: Chronic pain is a widespread and debilitating condition, encountered by
      physicians in a variety of practice settings. Although many pharmacologic and
      behavioral strategies exist for the management of this condition, treatment is
      often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying
      technique that utilizes trans-cutaneous electrical stimulation of pain fibers
      with the intent of re-organizing maladaptive signaling pathways. This review was
      conducted to further evaluate what is known regarding the mechanisms and
      mechanics of Scrambler Therapy and to investigate the preliminary data pertaining
      to the efficacy of this treatment modality. METHODS: The PubMed/Medline, SCOPUS,
      EMBASE, and Google Scholar databases were searched for all articles published on
      Scrambler Therapy prior to November 2015. All case studies and clinical trials
      were evaluated and reported in a descriptive manner. RESULTS: To date, 20
      reports, of varying scientific quality, have been published regarding this
      device; all but one small study, published only as an abstract, provided results
      that appear positive. CONCLUSION: The positive findings from preliminary studies
      with Scrambler Therapy support that this device provides benefit for patients
      with refractory pain syndromes. Larger, randomized studies are required to
      further evaluate the efficacy of this approach.

PMID- 27041743
TI  - Tailoring the core electron density in modulation-doped core-multi-shell
      nanowires.
AB  - We show how a proper radial modulation of the composition of core-multi-shell
      nanowires (NWs) critically enhances the control of the free-carrier density in
      the high-mobility core with respect to core-single-shell structures, thus
      overcoming the technological difficulty of fine tuning the remote doping density.
      We calculate the electron population of the different NW layers as a function of
      the doping density and of several geometrical parameters by means of a self
      consistent Schrodinger-Poisson approach: free carriers tend to localize in the
      outer shell and screen the core from the electric field of the dopants.

PMID- 27041742
TI  - Risk of secondary lymphedema in breast cancer survivors is related to serum
      phospholipid fatty acid desaturation.
AB  - PURPOSE: Secondary lymphedema is a common irreversible side effect of breast
      cancer surgery. We investigated if risk of secondary lymphedema in breast cancer
      survivors was related to changes in serum phospholipid fatty acid composition.
      METHODS: Study subjects were voluntarily recruited into the following three
      groups: breast cancer survivors who had sentinel lymph node biopsy without
      lymphedema (SLNB), those who had auxillary lymph node dissection without
      lymphedema (ALND), and those who had ALND with lymphedema (ALND + LE). Body mass
      index (BMI), serum lipid profiles, bioimpedance data with single-frequency
      bioimpedance analysis (SFBIA), and serum phospholipid compositions were analyzed
      and compared among the groups. RESULTS: BMI, serum total cholesterol (total-C),
      and low-density lipoprotein cholesterol (LDL-C) and SFBIA ratios increased only
      in the ALND + LE. High polyunsaturated fatty acids (PUFAs) and high C20:4 to
      C18:2 n-6 PUFAs (arachidonic acid [AA]/linoleic acid [LA]) was detected in the
      ALND and ALND + LE groups compared to SLNB. The ALND + LE group showed increased
      activity indices for delta 6 desaturase (D6D) and D5D and increased ratio of AA
      to eicosapentaenoic acid (AA/EPA) compared to the ALND and SLNB groups.
      Correlation and regression analysis indicated that D6D, D5D, and AA/EPA were
      associated with SFBIA ratios. CONCLUSION: We demonstrated that breast cancer
      survivors with lymphedema had elevated total PUFAs, fatty acid desaturase
      activity indices, and AA/EPA in serum phospholipids. Our findings suggested that
      desaturation extent of fatty acid composition might be related to the risk of
      secondary lymphedema in breast cancer survivors.

PMID- 27041744
TI  - Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated
      Naproxen/PEG3350 Solid Dispersions.
AB  - Solid dispersions have been used to enhance the bioavailability of poorly water
      soluble active pharmaceutical ingredients (APIs). However, the solid state phase,
      compositional uniformity, and scale-up problems are issues that need to be
      addressed. To allow for highly controllable products, the Drop Printing (DP)
      technique can provide precise dosages and predictable compositional uniformity of
      APIs in two/three dimensional structures. In this study, DP was used to prepare
      naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG
      coatings of different molecular weights (MW). A comparison of moisture
      accelerated crystallization inhibition by different PEG coatings was assessed.
      Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy,
      and differential scanning calorimetry (DSC) analysis were performed to
      characterize the morphology and quantify the apparent crystallinity of NAP within
      the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure
      the water content within each sample. The results suggest that the moisture
      accelerated crystallization inhibition capability of the PEG coatings increased
      with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of
      DP technology on manufacturing formulation, multilayer tablets with different PEG
      serving as barrier layers were also constructed, and their dissolution behavior
      was examined. By applying DP and appropriate materials, it is possible to design
      various carrier devices used to control the release dynamics of the API.

PMID- 27041745
TI  - Ancestry Matters: Patrilineage Growth and Extinction.
AB  - Patrilineality, the organization of kinship, inheritance, and other key social
      processes based on patrilineal male descent, has been a salient feature of social
      organization in China and many other societies for centuries. Because continuity
      or growth of the patrilineage was the central focus of reproductive strategies in
      such societies, we introduce the number of patrilineal male descendants
      generations later as a stratification outcome. By reconstructing and analyzing
      20,000 patrilineages in two prospective, multi-generational population databases
      from 18th and 19th century China, we show that patrilineages founded by high
      status males had higher growth rates for the next 150 years. The elevated growth
      rate of these patrilineages was due more to their having a lower probability of
      extinction at each point in time than to surviving patrilineal male descendants
      having larger numbers of sons on average. As a result, patrilineal male
      descendants of high status males account for a disproportionately large share of
      the male population in later generations. In China and elsewhere, patrilineal kin
      network characteristics influence individuals' life chances; thus effects of a
      male founder's characteristics on patrilineage size many generations later
      represent an indirect channel of status transmission that has not been considered
      previously.

PMID- 27041746
TI  - A field test of female mate preference for male plumage coloration in eastern
      bluebirds.
AB  - A growing body of evidence shows that female birds use male plumage coloration as
      an important criterion in mate choice. In the field, however, males with brighter
      coloration may both compete better for high quality territories and be the object
      of female choice. Positive associations between territory quality, male-male
      competitive ability, and female preferences can make it difficult to determine
      whether females actively choose the most ornamented males. Male eastern bluebirds
      (Sialia sialis) display brilliant ultraviolet (UV)-blue plumage coloration on
      their heads, backs, wings, and tails, and chestnut coloration on their breasts
      which is positively correlated with condition, reproductive effort, and
      reproductive success. We tested the hypothesis that female bluebirds prefer males
      that display brighter and more chromatic coloration by widowing males in the
      field and allowing replacement females to choose partners. We controlled for the
      influence of territory quality on female choice by widowing dyads of males with
      adjacent territories. We found no evidence that UV-blue or chestnut plumage
      coloration, body size, or body condition predicted the male with which females
      would pair. We found no support for the hypothesis that the coloration of male
      eastern bluebirds functions as a criterion in female mate choice.

PMID- 27041747
TI  - Former CVJ editor-in-chief - Dr. W. C. Douglas Hare (1925-2016).

PMID- 27041748
TI  - Position of conflict and scripting an antibiotic - A reply to Dr. Radke's comment
      (CVJ 2016;57:225).

PMID- 27041749
TI  - Treatment of Fish - A comment.

PMID- 27041750
TI  - Treatment of Fish - A reply.

PMID- 27041751
TI  - One Medicine, One Health, One World.

PMID- 27041752
TI  - Ethical question of the month - April 2016.

PMID- 27041753
TI  - Identification of microfilaria in a mammary mass aspirate from a female dog.
AB  - A filarial nematode larva (microfilaria) was found in an aspirate of a mammary
      mass from a dog imported to Saskatchewan from Myanmar. This was an unusual
      location for a microfilaria and numerous filarial nematodes infecting dogs in
      Asia had to be considered. This report describes the laboratory diagnosis of
      canine heartworm disease in this dog. 

PMID- 27041754
TI  - Malignant transformation of a unicameral bone cyst in a cat.
AB  - A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest
      cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging,
      surgical exploration, and histopathology. Surgical curettage and incorporation of
      bone cement led to full recovery. An osteosarcoma developed at the surgical site
      17 months later. Thoracic radiographs showed pulmonary lesions consistent with
      metastasis. 

PMID- 27041755
TI  - Emphysematous pyelitis and cystitis associated with vesicoureteral reflux in a
      diabetic dog.
AB  - A 12-year-old female dog with a 3-month history of poor response to diabetes
      treatment had an acute worsening of symptoms, including weakness and blindness.
      The dog had elevated blood glucose, alkaline phosphatase and urea concentration,
      hyposthenuria, glycosuria, hematuria, and pyuria. Escherichia coli was isolated
      from the urine. Radiographs and ultrasound examination showed that the dog had
      unilateral emphysematous pyelitis and concurrent cystitis associated with
      vesicoureteral reflux. 

PMID- 27041756
TI  - Clinical features of hypoadrenocorticism in soft-coated wheaten terrier dogs: 82
      cases (1979-2013).
AB  - The objective of this retrospective case series, which included 82 client-owned
      soft-coated wheaten terriers, was to characterize clinical features of
      hypoadrenocorticism in this breed. Median age at diagnosis was 3.5 years. There
      was no gender predilection. Clinicopathologic findings included sodium/potassium
      ratio < 27 (85%), hyperkalemia (76%), hyponatremia (63%), elevated blood urea
      nitrogen (83%) or creatinine (71%), and hypercalcemia (36%). Nine dogs with
      normal sodium and potassium (11%) were older and less often azotemic,
      hyperphosphatemic, or hypercalcemic. Twenty-one dogs (26%) developed protein
      losing nephropathy (n = 18) and/or end-stage renal disease (n = 3). Overall
      median survival time was 5.4 years, but was shorter in dogs with normal sodium
      and potassium at diagnosis (4.2 years), or those with subsequent protein-losing
      nephropathy (4.2 years). This population showed no gender predilection, unlike
      that reported in the general canine population with hypoadrenocorticism, and more
      comorbid protein-losing nephropathy than in the general soft-coated wheaten
      terrier population. 

PMID- 27041757
TI  - Comparison of perioperative and short-term postoperative complications of
      gastrointestinal biopsies via laparoscopic-assisted technique versus laparotomy.
AB  - This retrospective report describes perioperative and short-term postoperative
      complications of gastrointestinal biopsies obtained via a laparoscopic-assisted
      technique compared with laparotomy in a population of 60 client-owned dogs and
      cats with naturally occurring gastrointestinal disease. The medical records were
      examined for patients that underwent surgery for diagnostic gastrointestinal
      biopsies. Data were collected regarding perioperative complications such as
      hypotension, hypercarbia, and hypoxemia, and short-term postoperative
      complications including seroma and incisional infection/inflammation. The
      perioperative complication rate was 17.6% for the laparoscopically assisted group
      and 16.6% for the control group. The short-term postoperative complication rate
      was 5.9% for the laparoscopically assisted group and 0% for the control group.
      There was a 0% rate of intestinal dehiscence. There were no statistically
      significant differences in complication rates between the 2 groups, showing that
      laparoscopic-assisted gastrointestinal biopsies can be performed with acceptable
      perioperative and short-term postoperative complication rates. 

PMID- 27041758
TI  - Distribution of lameness lesions in beef cattle: A retrospective analysis of 745
      cases.
AB  - The objective of this retrospective study was to characterize the relative
      prevalence of diagnoses and location of lameness lesions in beef cattle. Medical
      records from 2005 to 2012 were reviewed and 745 cases of beef cattle that had
      presented for lameness were identified. Information regarding signalment, lesion
      location, and cause of lameness was analyzed. The cause of lameness was localized
      to the foot in approximately 85% of cases; a hind limb was affected over 70% of
      the time. The lateral claw was most commonly affected in cases of both fore- and
      hind-limb lameness. The most common diagnoses of noninfectious etiology were
      screw claw, vertical fissure, and interdigital fibroma. Infectious foot disease
      accounted for only 20% of foot lameness. Routine foot trimming may be warranted
      in some herds to improve weight-bearing balance and alleviate lameness. 

PMID- 27041759
TI  - Effectiveness of combined acupuncture and manual therapy relative to no treatment
      for canine musculoskeletal pain.
AB  - Despite the rise in popularity of both acupuncture and manual therapy in
      veterinary medicine, and the increasing number of Canadian veterinarians
      practising these techniques, there is little research demonstrating their
      effectiveness. In this repeated measures, therapeutic trial, 47 client-owned dogs
      with naturally occurring lameness were assessed for clinical response to
      treatment. Owners were blinded to the treatment schedule and completed
      questionnaires to assess their dogs' comfort and mobility. Comparison between pre
      and post-treatment results demonstrated that combined acupuncture and manual
      therapy provides immediate short-term improvement in comfort and mobility, as
      demonstrated by owner observed changes in play behavior (P = 0.015), walking (P <
      0.001), trotting (P = 0.002), jumping (P < 0.001), descending stairs (P = 0.003),
      rising from a lying position (P < 0.001), and reduced stiffness after rest (P <
      0.001) or following exercise (P < 0.001). Mood and attitude also improved, but
      did not attain statistical significance. 

PMID- 27041760
TI  - Major complications associated with fork-based and screw-based tibial tuberosity
      advancement implants: 438 cases.
AB  - This study reports major complications in a large cohort of dogs following tibial
      tuberosity advancement using either a fork-based or a screw-based implant system.
      Four hundred thirty-eight stifles were included in the study and major
      complications occurred in 51 stifles. Explanatory variables evaluated included
      implant type and body weight. No variables evaluated were associated with major
      complications. 

PMID- 27041761
TI  - Acute lead poisoning in western Canadian cattle - A 16-year retrospective study
      of diagnostic case records.
AB  - This study describes the epidemiology of acute lead poisoning in western Canadian
      cattle over the 16-year period of 1998 to 2013 and reports background bovine
      tissue lead concentrations. Case records from Prairie Diagnostic Services,
      Western College of Veterinary Medicine, identified 525 cases of acute lead
      toxicity over the investigational period. Poisonings were influenced by year (P <
      0.0001) and month (P < 0.0001). Submissions were highest in 2009 (15.6%), 2001
      (11.2%), and 2006 (9.9%). Most cases were observed during May, June, and July
      (62.3%). Cattle 6 months of age and younger were frequently poisoned (53.5%; P <
      0.0001). Beef breeds were predominantly poisoned. Mean toxic lead concentrations
      (mg/kg wet weight) in the blood, liver, and kidney were 1.30 +/- 1.70 (n = 301),
      33.5 +/- 80.5 (n = 172), and 56.3 +/- 39.7 (n = 61). Mean normal lead
      concentrations in the blood, liver, and kidney were 0.036 +/- 0.003 mg/kg (n=
      1081), 0.16 +/- 0.63 mg/kg (n = 382), and 0.41 +/- 0.62 mg/kg (n = 64). 

PMID- 27041762
TI  - Clinical results of single-session bilateral medial patellar luxation repair in
      26 small breed dogs.
AB  - Medical records of 26 small breed dogs treated with single-session bilateral
      medial patellar luxation repair were reviewed. Excluding dogs with complications
      associated with cranial cruciate ligament disease, 20/21 dogs with long-term
      follow-up achieved a complete or acceptable clinical recovery. The complication
      rate was not increased compared to that previously reported for unilateral
      patellar luxation repair. 

PMID- 27041763
TI  - Phaeohyphomycosis due to Pyrenophora phaeocomes and Drechslera nobleae in an
      Appaloosa mare.
AB  - A 21-year-old Appaloosa mare was presented with a pigmented cutaneous mass at the
      base of the right side of the neck. The diagnosis of phaeohyphomycosis due to
      pigmented fungi, known as Pyrenophora phaeocomes and Drechslera nobleae, was made
      based on a histopathology report followed by polymerase chain reaction (PCR) and
      18S rRNA gene sequencing. The mass was surgically excised with clean margins,
      which is usually curative. 

PMID- 27041764
TI  - Boundaries, perspective, and confidence.

PMID- 27041765
TI  - Exaggerated communication.

PMID- 27041766
TI  - Critical Essay: Building new management theories on sound data? The case of
      neuroscience.
AB  - In this critical essay, I contend that accelerating demands for novel theories in
      management studies imply that new methodologies and data are sometimes accepted
      prematurely as supply of these novel theories. This point is illustrated with
      reference to how neuroscience can inform management research. I propose two
      demand forces that foster the increased focus on neuroscience in management
      studies, these being (i) the direction of public research funding, and (ii)
      publication bias as a boost for journal impact factor. Looking at the supply
      side, I note that (i) the statistical power of studies using functional magnetic
      resonance imaging (or fMRI, the 'gold' standard) is unacceptably low, (ii) the
      use of imprecise 'motherhood' statements, and (iii) the dismissal of ethical
      concerns in the formulation of management theories and practice informed by
      neuroscience. I then briefly outline the bad consequences of this for management
      theory and practice, emphasize why it is important to prevent these consequences,
      and offer some methodological suggestions for future research.

PMID- 27041767
TI  - TandemPET- A High Resolution, Small Animal, Virtual Pinhole-Based PET Scanner:
      Initial Design Study.
AB  - Mice are the perhaps the most common species of rodents used in biomedical
      research, but many of the current generation of small animal PET scanners are non
      optimal for imaging these small rodents due to their relatively low resolution.
      Consequently, a number of researchers have investigated the development of high
      resolution scanners to address this need. In this investigation, the design of a
      novel, high-resolution system based on the dual-detector, virtual-pinhole PET
      concept was explored via Monte Carlo simulations. Specifically, this system,
      called TandemPET, consists of a 5 cm * 5 cm high-resolution detector made-up of a
      90 * 90 array of 0.5 mm * 0.5 mm * 10 mm (pitch= 0.55 mm) LYSO detector elements
      in coincidence with a lower resolution detector consisting of a 68 * 68 array of
      1.5 mm * 1.5 mm * 10 mm LYSO detector elements (total size= 10.5 cm * 10.5 cm).
      Analyses indicated that TandemPET's optimal geometry is to position the high
      resolution detector 3 cm from the center-of-rotation, with the lower resolution
      detector positioned 9 cm from center. Measurements using modified NEMA NU4-2008
      based protocols revealed that the spatial resolution of the system is ~0.5 mm
      FWHM, after correction of positron range effects. Peak sensitivity is 2.1%, which
      is comparable to current small animal PET scanners. Images from a digital mouse
      brain phantom demonstrated the potential of the system for identifying important
      neurological structures.

PMID- 27041768
TI  - An Extended Bayesian-FBP Algorithm.
AB  - Recently we developed a Bayesian-FBP (Filtered Backprojection) algorithm for CT
      image reconstruction. This algorithm is also referred to as the FBP-MAP (FBP
      Maximum a Posteriori) algorithm. This non-iterative Bayesian algorithm has been
      applied to real-time MRI, in which the k-space is under-sampled. This current
      paper investigates the possibility to extend this Bayesian-FBP algorithm by
      introducing more controlling parameters. Thus, our original Bayesian-FBP
      algorithm became a special case of the extended Bayesian-FBP algorithm. A cardiac
      patient data set is used in this paper to evaluate the extended Bayesian-FBP
      algorithm, and the result from a well-establish iterative algorithm with L1-norms
      is used as the gold standard. If the parameters are selected properly, the
      extended Bayesian-FBP algorithm can outperform the original Bayesian-FBP
      algorithm.

PMID- 27041769
TI  - Small beetle, large-scale drivers: how regional and landscape factors affect
      outbreaks of the European spruce bark beetle.
AB  - 1. Unprecedented bark beetle outbreaks have been observed for a variety of forest
      ecosystems recently, and damage is expected to further intensify as a consequence
      of climate change. In Central Europe, the response of ecosystem management to
      increasing infestation risk has hitherto focused largely on the stand level,
      while the contingency of outbreak dynamics on large-scale drivers remains poorly
      understood. 2. To investigate how factors beyond the local scale contribute to
      the infestation risk from Ips typographus (Col., Scol.), we analysed drivers
      across seven orders of magnitude in scale (from 103 to 1010 m2) over a 23-year
      period, focusing on the Bavarian Forest National Park. Time-discrete hazard
      modelling was used to account for local factors and temporal dependencies.
      Subsequently, beta regression was applied to determine the influence of regional
      and landscape factors, the latter characterized by means of graph theory. 3. We
      found that in addition to stand variables, large-scale drivers also strongly
      influenced bark beetle infestation risk. Outbreak waves were closely related to
      landscape-scale connectedness of both host and beetle populations as well as to
      regional bark beetle infestation levels. Furthermore, regional summer drought was
      identified as an important trigger for infestation pulses. Large-scale synchrony
      and connectivity are thus key drivers of the recently observed bark beetle
      outbreak in the area. 4.Synthesis and applications. Our multiscale analysis
      provides evidence that the risk for biotic disturbances is highly dependent on
      drivers beyond the control of traditional stand-scale management. This finding
      highlights the importance of fostering the ability to cope with and recover from
      disturbance. It furthermore suggests that a stronger consideration of landscape
      and regional processes is needed to address changing disturbance regimes in
      ecosystem management.

PMID- 27041770
TI  - Plasma carotenoid concentrations of incubating American kestrels (Falco
      sparverius) show annual, seasonal, and individual variation and explain
      reproductive outcome.
AB  - In wild birds, the proximate and ultimate factors that affect circulating
      carotenoid concentrations remain poorly understood. We studied variation in
      plasma carotenoid concentrations across several scales: annual, seasonal, pair,
      territory and individual, and evaluated whether carotenoid levels explained
      reproductive outcome of wild American kestrels (Falco sparverius). We sampled
      plasma carotenoid concentrations of 99 female and 80 male incubating kestrels
      from April-June in 2008-2012. Plasma carotenoid concentrations were explained by
      an interaction between year and sex, date, and random effects for pair and
      individual identity. In general, plasma carotenoid concentrations of males were
      significantly higher than females, but this depended on year. Within a breeding
      season, earlier nesting kestrels had higher carotenoid concentrations than later
      nesting kestrels, a pattern that is coincident with seasonal trends in local
      fitness. Pair and individual identity explained variation in carotenoid
      concentrations suggesting that carotenoid concentrations of mated birds were
      correlated, and some individuals consistently maintained higher carotenoid levels
      than others. Male carotenoid concentrations were positively associated with
      number of young fledged per pair. These results are consistent with the
      hypothesis that higher quality individuals have higher carotenoid levels compared
      to lower quality individuals, despite annual variations in carotenoid
      availability.

PMID- 27041771
TI  - RAFT polymerization of temperature- and salt-responsive block copolymers as
      reversible hydrogels.
AB  - Reversible-addition fragmentation chain transfer (RAFT) polymerization enabled
      the synthesis of novel, stimuli-responsive, AB and ABA block copolymers. The B
      block contained oligo(ethylene glycol) methyl ether methacrylate (OEG) and was
      permanently hydrophilic in the conditions examined. The A block consisted of
      diethylene glycol methyl ether methacrylate (DEG) and [2
      (methacryloyloxy)ethyl]trimethylammonium chloride (TMA). The A block displayed
      both salt- and temperature-response with lower critical solution temperatures
      (LCSTs) dependent on the molar content of TMA and the presence of salt. Higher
      TMA content in the AB diblock copolymers increased the critical micelle
      temperatures (CMT) in HPLC-grade water due to an increased hydrophilicity of the
      A block. Upon addition of 0.9 wt% NaCl, the CMTs of poly(OEG-b-DEG95TMA5)
      decreased from 50  degrees C to 36  degrees C due to screening of electrostatic
      repulsion between the TMA units. ABA triblock copolymers displayed excellent
      hydrogel properties with salt- and temperature-dependent gel points. TMA
      incorporation in the A block increased the gel points for all triblock
      copolymers, and salt-response increased with higher TMA composition in the A
      block. For example, poly(DEG98TMA2-b-OEG-b-DEG98TMA2) formed a hydrogel at 40 
      degrees C in HPLC-grade water and 26  degrees C in 0.9 wt% NaCl aqueous solution.
      These salt- and temperature-responsive AB diblock and ABA triblock copolymers
      find applications as drug delivery vehicles, adhesives, and hydrogels.

PMID- 27041772
TI  - A Two Sample Distribution-Free Test for Functional Data with Application to a
      Diffusion Tensor Imaging Study of Multiple Sclerosis.
AB  - Motivated by an imaging study, this paper develops a nonparametric testing
      procedure for testing the null hypothesis that two samples of curves observed at
      discrete grids and with noise have the same underlying distribution. The
      objective is to formally compare white matter tract profiles between healthy
      individuals and multiple sclerosis patients, as assessed by conventional
      diffusion tensor imaging measures. We propose to decompose the curves using
      functional principal component analysis of a mixture process, which we refer to
      as marginal functional principal component analysis. This approach reduces the
      dimension of the testing problem in a way that enables the use of traditional
      nonparametric univariate testing procedures. The procedure is computationally
      efficient and accommodates different sampling designs. Numerical studies are
      presented to validate the size and power properties of the test in many realistic
      scenarios. In these cases, the proposed test has been found to be more powerful
      than its primary competitor. Application to the diffusion tensor imaging data
      reveals that all the tracts studied are associated with multiple sclerosis and
      the choice of the diffusion tensor image measurement is important when assessing
      axonal disruption.

PMID- 27041773
TI  - Two-stage model for time varying effects of zero-inflated count longitudinal
      covariates with applications in health behaviour research.
AB  - This study proposes a two-stage approach to characterize individual developmental
      trajectories of health risk behaviors and delineate their time-varying effects on
      short-term or long-term health outcomes. Our model can accommodate longitudinal
      covariates with zero-inflated counts and discrete outcomes. The longitudinal data
      of a well-known study of youth at high risk for substance abuse are presented as
      a motivating example to demonstrate the effectiveness of the model in delineating
      critical developmental periods of prevention and intervention. Our simulation
      study shows that the performance of the proposed model improves as the sample
      size or number of time points increases. When there are excess zeros in the data,
      the regular Poisson model cannot estimate either the longitudinal covariate
      process or its time-varying effect well. This result, therefore, emphasizes the
      important role that the proposed model plays in handling zero-inflation in the
      data.

PMID- 27041774
TI  - Connecting Life Span Development with the Sociology of the Life Course: A New
      Direction.
AB  - The life course has become a topic of growing interest within the social
      sciences. Attempts to link this sub-discipline with life span developmental
      psychology have been called for but with little sign of success. In this paper,
      we seek to address three interlinked issues concerning the potential for a more
      productive interchange between life course sociology and life span psychology.
      The first is to try to account for the failure of these two sub-disciplines to
      achieve any deepening engagement with each other, despite the long-expressed
      desirability of that goal; the second is to draw attention to the scope for
      enriching the sociology of the life course through Erik Erikson's model of life
      span development; and the last is the potential for linking Eriksonian theory
      with current debates within mainstream sociology about the processes involved in
      'individualisation' and 'self-reflexivity' as an alternative entry point to bring
      together these two fields of work.

PMID- 27041775
TI  - Outsourcing Elderly Care to Migrant Workers: The Impact of Gender and Class on
      the Experience of Male Employers.
AB  - This article, based on semi-structured interviews, addresses masculinity in the
      international division of reproductive labour through an analysis of the impact
      of gender and class on the outsourcing of elderly care services to migrant care
      workers. In the Italian context, characterised by a limited provision of long
      term care services and by cash-for-care benefits, the strategies of men as
      employers of migrant care workers are shaped by class and gender. The outsourcing
      of care to migrant workers reproduces hegemonic masculinity in so far as male
      employers are able to withdraw from the 'dirty work'. At the same time, men
      engage with tasks which are, in principle, kept at a distance. The employers'
      family status, combined with their class background, are crucial factors in
      shaping the heterogeneity of men's experiences as employers and managers of care
      labour, and the ways in which they make sense of their masculinity.

PMID- 27041776
TI  - Synthesis of 2-aryl-2H-tetrazoles via a regioselective [3+2] cycloaddition
      reaction.
AB  - A regioselective cycloaddition reaction of arenediazonium salts with
      trimethylsilyldiazomethane is reported. A series of 2-aryltetrazoles were
      obtained in good to moderate yields with wide functional group compatibility.
      Furthermore, this cycloaddition reaction opens the way to build up the versatile
      intermediate 2-aryl-5-bromotetrazole.

PMID- 27041777
TI  - Development of a Measure of Hepatitis C-alcohol Knowledge.
AB  - Alcohol use by persons with hepatitis C (HCV) increases the risk of cirrhosis and
      hepatocellular carcinoma, yet no measures on knowledge of the effects of alcohol
      use on HCV have been published. We developed 7 items assessing knowledge of the
      relationship between HCV and alcohol use. We enrolled 53 patients with HCV and
      risky alcohol use in an HCV-alcohol treatment study. All 53 participants
      completed a baseline interview, with 35 and 45 participants completing additional
      interviews at three and six months, respectively. We used generalized estimating
      equations (GEE) regression to account for non-independence of subjects and
      attrition. We assessed changes in HCV-alcohol knowledge at three and six months
      compared to baseline. Knowledge significantly increased at three months, compared
      to baseline (beta=0.392, p=0.005), and had a trend toward significance at six
      months, compared to baseline (beta=0.232, p=0.074). We also tested for between
      subject differences in HCV-alcohol knowledge by demographic variables. HCV
      alcohol knowledge did not significantly vary by gender, age, baseline HIV status,
      or baseline depression. Participants with higher educational attainment
      (beta=0.052, p=0.057) had a trend toward significantly higher HCV-alcohol
      knowledge scores, and White participants had higher HCV-alcohol knowledge scores
      (beta=0.349, p=0.002) than participants of all other races combined. In a second
      GEE regression model, we examined the relationship between change in HCV-alcohol
      knowledge and change in alcohol use severity scores over time. Increases in one's
      HCV-alcohol knowledge score were significantly related to greater reductions in
      alcohol use severity scores (beta=-0.052, p=0.027). Thus, the seven-item HCV
      alcohol Knowledge Scale successfully identified changes in HCV-alcohol knowledge
      after exposure to HCV-alcohol education. In addition, improvements in HCV-alcohol
      knowledge, as assessed by the scale, predicted decreases in alcohol use over
      time. These findings support the use of the HCV-alcohol Knowledge Scale as both a
      research and clinical tool.

PMID- 27041778
TI  - OPTIMAL SHRINKAGE ESTIMATION OF MEAN PARAMETERS IN FAMILY OF DISTRIBUTIONS WITH
      QUADRATIC VARIANCE.
AB  - This paper discusses the simultaneous inference of mean parameters in a family of
      distributions with quadratic variance function. We first introduce a class of
      semi-parametric/parametric shrinkage estimators and establish their asymptotic
      optimality properties. Two specific cases, the location-scale family and the
      natural exponential family with quadratic variance function, are then studied in
      detail. We conduct a comprehensive simulation study to compare the performance of
      the proposed methods with existing shrinkage estimators. We also apply the method
      to real data and obtain encouraging results.

PMID- 27041779
TI  - Non-negative matrix analysis in x-ray spectromicroscopy: choosing regularizers.
AB  - In x-ray spectromicroscopy, a set of images can be acquired across an absorption
      edge to reveal chemical speciation. We previously described the use of non
      negative matrix approximation methods for improved classification and analysis of
      these types of data. We present here an approach to find appropriate values of
      regularization parameters for this optimization approach.

PMID- 27041780
TI  - A modified ziggurat algorithm for generating exponentially- and normally
      distributed pseudorandom numbers.
AB  - The Ziggurat Algorithm is a very fast rejection sampling method for generating
      PseudoRandom Numbers (PRNs) from statistical distributions. In the algorithm,
      rectangular sampling domains are layered on top of each other (resembling a
      ziggurat) to encapsulate the desired probability density function. Random values
      within these layers are sampled and then returned if they lie beneath the graph
      of the probability density function. Here, we present an implementation where
      ziggurat layers reside completely beneath the probability density function,
      thereby eliminating the need for any rejection test within the ziggurat layers.
      In the new algorithm, small overhanging segments of probability density remain to
      the right of each ziggurat layer, which can be efficiently sampled with
      triangularly-shaped sampling domains. Median runtimes of the new algorithm for
      exponential and normal variates is reduced to 58% and 53% respectively
      (collective range: 41-93%). An accessible C library, along with extensions into
      Python and MATLAB/Octave are provided.

PMID- 27041781
TI  - Influences of selective adaptation on perception of audiovisual speech.
AB  - Research suggests that selective adaptation in speech is a low-level process
      dependent on sensory-specific information shared between the adaptor and test
      stimuli. However, previous research has only examined how adaptors shift
      perception of unimodal test stimuli, either auditory or visual. In the current
      series of experiments, we investigated whether adaptation to cross-sensory
      phonetic information can influence perception of integrated audio-visual phonetic
      information. We examined how selective adaptation to audio and visual adaptors
      shift perception of speech along an audiovisual test continuum. This test
      continuum consisted of nine audio-/ba/-visual-/va/ stimuli, ranging in visual
      clarity of the mouth. When the mouth was clearly visible, perceivers "heard" the
      audio-visual stimulus as an integrated "va" percept 93.7% of the time (e.g.,
      McGurk & MacDonald, 1976). As visibility of the mouth became less clear across
      the nine-item continuum, the audio-visual "va" percept weakened, resulting in a
      continuum ranging in audio-visual percepts from /va/ to /ba/. Perception of the
      test-stimuli was tested before and after adaptation. Changes in audiovisual
      speech perception were observed following adaptation to visual-/va/ and
      audiovisual-/va/, but not following adaptation to auditory-/va/, auditory-/ba/,
      or visual-/ba/. Adaptation modulates perception of integrated audio-visual speech
      by modulating the processing of sensory-specific information. The results suggest
      that auditory and visual speech information are not completely integrated at the
      level of selective adaptation.

PMID- 27041782
TI  - Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating
      Cognitive, Genetic, and Clinical Influences on Stress Reactivity.
AB  - Despite decades of research examining diathesis-stress models of emotional
      disorders, it remains unclear whether dysfunctional attitudes interact with
      stressful experiences to shape affect on a daily basis and, if so, how clinical
      and genetic factors influence these associations. To address these issues, we
      conducted a multi-level daily diary study that examined how dysfunctional
      attitudes and stressful events relate to daily fluctuations in negative and
      positive affect in 104 young adults. Given evidence that clinical and genetic
      factors underlie stress sensitivity, we also examined how daily affect is
      influenced by internalizing and externalizing symptoms and brain-derived
      neurotrophic factor (BDNF) genotype, which have been shown to influence neural,
      endocrine, and affective responses to stress. In multivariate models,
      internalizing symptoms and BDNF Val66Met genotype independently predicted
      heightened negative affect on stressful days, but dysfunctional attitudes did
      not. Specifically, the BDNF Met allele and elevated baseline internalizing
      symptomatology predicted greater increases in negative affect in stressful
      circumstances. These data are the first to demonstrate that BDNF genotype and
      stress are jointly associated with daily fluctuations in negative affect, and
      they challenge the assumption that maladaptive beliefs play a strong independent
      role in determining affective responses to everyday stressors. The results may
      thus inform the development of new multi-level theories of psychopathology and
      guide future research on predictors of affective lability.

PMID- 27041783
TI  - Using Emotion as Information in Future-Oriented Cognition: Individual Differences
      in the Context of State Negative Affect.
AB  - Predictions about the future are susceptible to mood-congruent influences of
      emotional state. However, recent work suggests individuals also differ in the
      degree to which they incorporate emotion into cognition. This study examined the
      role of such individual differences in the context of state negative emotion. We
      examined whether trait tendencies to use negative or positive emotion as
      information affect individuals' predictions of what will happen in the future
      (likelihood estimation) and how events will feel (affective forecasting), and
      whether trait influences depend on emotional state. Participants (N=119) reported
      on tendencies to use emotion as information ("following feelings"), underwent an
      emotion induction (negative versus neutral), and made likelihood estimates and
      affective forecasts for future events. Views of the future were predicted by both
      emotional state and individual differences in following feelings. Whereas
      following negative feelings affected most future-oriented cognition across
      emotional states, following positive feelings specifically buffered individuals'
      views of the future in the negative emotion condition, and specifically for
      positive future events, a category of future-event prediction especially
      important in psychological health. Individual differences may confer
      predisposition toward optimistic or pessimistic expectations of the future in the
      context of acute negative emotion, with implications for adaptive and maladaptive
      functioning.

PMID- 27041784
TI  - Understanding semantic and phonological processing deficits in adults with
      aphasia: Effects of category and typicality.
AB  - BACKGROUND: Semantic and phonological processing deficits are often present in
      aphasia. The degree of interdependence between the deficits has been widely
      studied with variable findings. Semantic variables such as category and
      typicality have been found to influence semantic processing in healthy
      individuals and persons with aphasia but their influence on phonological
      processing is unknown. AIMS: This study examined the nature of semantic and
      phonological access in aphasia by comparing adults with aphasia to healthy
      control participants. Semantic and phonological tasks were used to assess the
      difference in processing requirements between and within each group as well as
      examine the effects of category and typicality on different stages of semantic
      and phonological processing. METHODS & PROCEDURES: Thirty-two persons with
      aphasia and ten neurologically healthy adults were administered nine tasks:
      Category Superordinate, Category Coordinate, Semantic Feature, Rhyme Judgment (No
      Name), Syllable Judgment (No-Name), Phoneme Verification (No-Name), Rhyme
      Judgment (Name-Provided), Syllable Judgment (Name-Provided), and Phoneme
      Verification (Name-Provided). Accuracy and reaction time data were collected for
      each of these tasks and between-group and within-group differences were analyzed
      via MANOVA/MANCOVA and hierarchical clustering analyses. OUTCOMES & RESULTS:
      Persons with aphasia performed with significantly lower accuracy than controls on
      phonological tasks but performed comparably on semantic tasks. Participants with
      aphasia were significantly slower than controls on all semantic and phonological
      tasks. Clustering of the nine tasks by accuracy revealed different processing
      requirements in the participants with aphasia compared to the control group while
      clustering by reaction time revealed similar trends in both groups in that
      phonological (no-name) items required the most processing time. Significant
      effects of category and typicality were noted in the semantic tasks but not in
      any of the phonological tasks. CONCLUSIONS: Individuals with aphasia demonstrated
      overall impaired phonological processing with relatively preserved semantic
      processing as compared to controls. Per accuracy and reaction time measures,
      distinct trends in processing load for semantic tasks versus phonological tasks
      were seen in the individuals with aphasia whereas only speed of processing and
      not accuracy was impacted by phonological processing load in the control group.
      The results align most closely with discrete serial processing models of lexical
      processing as category and typicality effects were robust in the semantic tasks
      but not in any of the phonological tasks. Alternative explanations for these
      results also are discussed.

PMID- 27041785
TI  - Segregation as a multi-scalar phenomenon and its implications for neighborhood
      scale research: the case of South Seattle 1990-2010.
AB  - Neighborhoods and neighborhood change are often at least implicitly understood in
      relation to processes taking place at scales both smaller than and larger than
      the neighborhood itself. Until recently our capacity to represent these multi
      scalar processes with quantitative measures has been limited. Recent work on
      "segregation profiles" by Reardon and collaborators (Reardon et al., 2008, 2009)
      expands our capacity to explore the relationship between population measures and
      scale. With the methodological tools now available, we need a conceptual shift in
      how we view population measures in order to bring our theories and measures of
      neighborhoods into alignment. I argue that segregation can be beneficially viewed
      as multi-scalar; not a value calculable at some 'correct' scale, but a continuous
      function with respect to scale. This shift requires new ways of thinking about
      and analyzing segregation with respect to scale that engage with the complexity
      of the multi-scalar measure. Using block level data for eight neighborhoods in
      Seattle, Washington I explore the implications of a multi-scalar segregation
      measure for understanding neighborhoods and neighborhood change from 1990 to
      2010.

PMID- 27041786
TI  - Dynamic finite-strain modelling of the human left ventricle in health and disease
      using an immersed boundary-finite element method.
AB  - Detailed models of the biomechanics of the heart are important both for
      developing improved interventions for patients with heart disease and also for
      patient risk stratification and treatment planning. For instance, stress
      distributions in the heart affect cardiac remodelling, but such distributions are
      not presently accessible in patients. Biomechanical models of the heart offer
      detailed three-dimensional deformation, stress and strain fields that can
      supplement conventional clinical data. In this work, we introduce dynamic
      computational models of the human left ventricle (LV) that are derived from
      clinical imaging data obtained from a healthy subject and from a patient with a
      myocardial infarction (MI). Both models incorporate a detailed invariant-based
      orthotropic description of the passive elasticity of the ventricular myocardium
      along with a detailed biophysical model of active tension generation in the
      ventricular muscle. These constitutive models are employed within a dynamic
      simulation framework that accounts for the inertia of the ventricular muscle and
      the blood that is based on an immersed boundary (IB) method with a finite element
      description of the structural mechanics. The geometry of the models is based on
      data obtained non-invasively by cardiac magnetic resonance (CMR). CMR imaging
      data are also used to estimate the parameters of the passive and active
      constitutive models, which are determined so that the simulated end-diastolic and
      end-systolic volumes agree with the corresponding volumes determined from the CMR
      imaging studies. Using these models, we simulate LV dynamics from enddiastole to
      end-systole. The results of our simulations are shown to be in good agreement
      with subject-specific CMR-derived strain measurements and also with earlier
      clinical studies on human LV strain distributions.

PMID- 27041787
TI  - Multi-channel beam-scanning imaging at kHz frame rates by Lissajous trajectory
      microscopy.
AB  - A beam-scanning microscope based on Lissajous trajectory imaging is described for
      achieving streaming 2D imaging with continuous frame rates up to 1.4 kHz. The
      microscope utilizes two fast-scan resonant mirrors to direct the optical beam on
      a circuitous trajectory through the field of view. By separating the full
      Lissajous trajectory time-domain data into sub-trajectories (partial,
      undersampled trajectories) effective frame-rates much higher than the repeat time
      of the Lissajous trajectory are achieved with many unsampled pixels present. A
      model-based image reconstruction (MBIR) 3D in-painting algorithm is then used to
      interpolate the missing data for the unsampled pixels to recover full images. The
      MBIR algorithm uses a maximum a posteriori estimation with a generalized Gaussian
      Markov random field prior model for image interpolation. Because images are
      acquired using photomultiplier tubes or photodiodes, parallelization for multi
      channel imaging is straightforward. Preliminary results show that when combined
      with the MBIR in-painting algorithm, this technique has the ability to generate
      kHz frame rate images across 6 total dimensions of space, time, and polarization
      for SHG, TPEF, and confocal reflective birefringence data on a multimodal imaging
      platform for biomedical imaging. The use of a multi-channel data acquisition card
      allows for multimodal imaging with perfect image overlay. Image blur due to
      sample motion was also reduced by using higher frame rates.

PMID- 27041788
TI  - Synchronous-digitization for Video Rate Polarization Modulated Beam Scanning
      Second Harmonic Generation Microscopy.
AB  - Fast beam-scanning non-linear optical microscopy, coupled with fast (8 MHz)
      polarization modulation and analytical modeling have enabled simultaneous
      nonlinear optical Stokes ellipsometry (NOSE) and linear Stokes ellipsometry
      imaging at video rate (15 Hz). NOSE enables recovery of the complex-valued Jones
      tensor that describes the polarization-dependent observables, in contrast to
      polarimetry, in which the polarization stated of the exciting beam is recorded.
      Each data acquisition consists of 30 images (10 for each detector, with three
      detectors operating in parallel), each of which corresponds to polarization
      dependent results. Processing of this image set by linear fitting contracts down
      each set of 10 images to a set of 5 parameters for each detector in second
      harmonic generation (SHG) and three parameters for the transmittance of the
      fundamental laser beam. Using these parameters, it is possible to recover the
      Jones tensor elements of the sample at video rate. Video rate imaging is enabled
      by performing synchronous digitization (SD), in which a PCIe digital oscilloscope
      card is synchronized to the laser (the laser is the master clock.) Fast
      polarization modulation was achieved by modulating an electro-optic modulator
      synchronously with the laser and digitizer, with a simple sine-wave at 1/10th the
      period of the laser, producing a repeating pattern of 10 polarization states.
      This approach was validated using Z-cut quartz, and NOSE microscopy was performed
      for micro-crystals of naproxen.

PMID- 27041789
TI  - Spectral X-Ray Diffraction using a 6 Megapixel Photon Counting Array Detector.
AB  - Pixel-array array detectors allow single-photon counting to be performed on a
      massively parallel scale, with several million counting circuits and detectors in
      the array. Because the number of photoelectrons produced at the detector surface
      depends on the photon energy, these detectors offer the possibility of spectral
      imaging. In this work, a statistical model of the instrument response is used to
      calibrate the detector on a per-pixel basis. In turn, the calibrated sensor was
      used to perform separation of dual-energy diffraction measurements into two
      monochromatic images. Targeting applications include multi-wavelength diffraction
      to aid in protein structure determination and X-ray diffraction imaging.

PMID- 27041790
TI  - Opportunities and limitations for combined fly-scan ptychography and fluorescence
      microscopy.
AB  - X-ray fluorescence offers unparalleled sensitivity for imaging the nanoscale
      distribution of trace elements in micrometer thick samples, while x-ray
      ptychography offers an approach to image light element containing structures at a
      resolution beyond that of the x-ray lens used. These methods can be used in
      combination, and in continuous scan mode for rapid data acquisition when using
      multiple probe mode reconstruction methods. We discuss here the opportunities and
      limitations of making use of additional information provided by ptychography to
      improve x-ray fluorescence images in two ways: by using position-error-correction
      algorithms to correct for scan distortions in fluorescence scans, and by
      considering the signal-to-noise limits on previously-demonstrated ptychographic
      probe deconvolution methods. This highlights the advantages of using a combined
      approach.

PMID- 27041791
TI  - Novel Use for DOG1 in Discriminating Breast Invasive Carcinoma from Noninvasive
      Breast Lesions.
AB  - AIMS: DOG1 has proven to be a useful marker of gastrointestinal stromal tumors
      (GISTs). Recently, DOG1 expression has also been reported in some non-GIST
      malignant tumors, but the details related to DOG1 expression in breast tissue
      remain unclear. The aim of this study was to detect the expression of DOG1 in the
      human breast and to evaluate the feasibility of using DOG1 to discriminate
      between invasive breast carcinoma and noninvasive breast lesions. METHODS AND
      RESULTS: A total of 210 cases, including both invasive and noninvasive breast
      lesions, were collected to assess DOG1 expression immunohistochemically. DOG1
      expression was consistently positive in breast myoepithelial cells (MECs), which
      was similar to the results obtained for three other MEC markers: calponin, smooth
      muscle myosin heavy chain (SMMHC), and P63 (P > 0.05 in all). Importantly, DOG1
      was useful in discriminating invasive breast carcinoma from noninvasive breast
      lesions (P < 0.05). CONCLUSIONS: DOG1 is a useful marker of breast MECs, and
      adding DOG1 to the MEC identification panel will provide more sophisticated
      information when diagnosing uncertain cases in the breast.

PMID- 27041792
TI  - The Serum Concentrations of Chemokine CXCL12 and Its Specific Receptor CXCR4 in
      Patients with Esophageal Cancer.
AB  - OBJECTIVES: Recent investigations have suggested that upregulated levels of
      inflammatory biomarkers, such as chemokines, may be associated with development
      of many malignancies, including esophageal cancer (EC). Based on our knowledge,
      this study is the first to assess the serum concentration of chemokine CXCL12 and
      its specific receptor CXCR4 in the diagnosis of EC patients. MATERIAL AND
      METHODS: The present study included 79 subjects: 49 patients with EC and 30
      healthy volunteers. The serum concentrations of CXCL12 and CXCR4 and classical
      tumor markers such as carcinoembryonal antigen (CEA) and squamous cell cancer
      antigen (SCC-Ag) were measured using immunoenzyme assays, while C-reactive
      protein (CRP) levels were assessed by immunoturbidimetric method. Moreover,
      diagnostic criteria of all proteins tested and the survival of EC patients were
      assessed. RESULTS: The serum concentrations of CXCL12 were significantly higher,
      while those of its receptor CXCR4 were significantly lower in EC patients
      compared to healthy controls. The diagnostic sensitivity, negative predictive
      value, and accuracy of CXCR4 were the highest among all analyzed proteins and
      increased for combined analysis with classical tumor markers and CRP levels.
      CONCLUSION: Our findings suggest that serum CXCR4 may improve the diagnosis of EC
      patients, especially in combination with classical tumor markers.

PMID- 27041793
TI  - Dynamic Treatment Effects.
AB  - This paper develops robust models for estimating and interpreting treatment
      effects arising from both ordered and unordered multistage decision problems.
      Identification is secured through instrumental variables and/or conditional
      independence (matching) assumptions. We decompose treatment effects into direct
      effects and continuation values associated with moving to the next stage of a
      decision problem. Using our framework, we decompose the IV estimator, showing
      that IV generally does not estimate economically interpretable or policy relevant
      parameters in prototypical dynamic discrete choice models, unless policy
      variables are instruments. Continuation values are an empirically important
      component of estimated total treatment effects of education. We use our analysis
      to estimate the components of what LATE estimates in a dynamic discrete choice
      model.

PMID- 27041794
TI  - Study of paramagnetic defect centers in as-grown and annealed TiO2 anatase and
      rutile nanoparticles by a variable-temperature X-band and high-frequency (236
      GHz) EPR.
AB  - Detailed EPR investigations on as-grown and annealed TiO2 nanoparticles in the
      anatase and rutile phases were carried out at X-band (9.6 GHz) at 77, 120-300 K
      and at 236 GHz at 292 K. The analysis of EPR data for as-grown and annealed
      anatase and rutile samples revealed the presence of several paramagnetic centers:
      Ti3+, O-, adsorbed oxygen (O2-) and oxygen vacancies. On the other hand, in as
      grown rutile samples, there were observed EPR lines due to adsorbed oxygen (O2-)
      and the Fe3+ ions in both Ti4+ substitutional positions, with and without
      coupling to an oxygen vacancy in the near neighborhood. Anatase nanoparticles
      were completely converted to rutile phase when annealed at 1000 degrees  C,
      exhibiting EPR spectra similar to those exhibited by the as-grown rutile
      nanoparticles. The high-frequency (236 GHz) EPR data on anatase and rutile
      samples, recorded in the region about g = 2.0 exhibit resolved EPR lines, due to
      O- and O2- ions enabling determination of their g-values with higher precision,
      as well as observation of hyperfine sextets due to Mn2+ and Mn4+ ions in anatase.

PMID- 27041795
TI  - The hazards of rapid approval of new drugs.

PMID- 27041796
TI  - Radiopharmaceuticals in breastfeeding.

PMID- 27041797
TI  - Iodine in breastfeeding.

PMID- 27041798
TI  - The management of gastro-oesophageal reflux disease.
AB  - If there are no features of serious disease, suspected gastro-oesophageal reflux
      disease can be initially managed with a trial of a proton pump inhibitor for 4-8
      weeks. This should be taken 30-60 minutes before food for optimal effect. Once
      symptoms are controlled, attempt to withdraw acid suppression therapy. If
      symptoms recur, use the minimum dose that controls symptoms. Patients who have
      severe erosive oesophagitis, scleroderma oesophagus or Barrett's oesophagus
      require long-term treatment with a proton pump inhibitor. Lifestyle modification
      strategies can help gastro-oesophageal reflux disease. Weight loss has the
      strongest evidence for efficacy. Further investigation and a specialist referral
      are required if there is no response to proton pump inhibitor therapy. Atypical
      symptoms or signs of serious disease also need investigation. 

PMID- 27041799
TI  - The pitfalls of prescribing for family and friends.
AB  - In most of Australia there is no legislation prohibiting medical practitioners
      from prescribing for family and friends. In South Australia it is prohibited to
      prescribe Schedule 8 drugs for family members unless it is a verifiable
      emergency. The Medical Board of Australia states medical practitioners should
      avoid providing medical care to anyone with whom they have a close personal
      relationship. Medical defence organisations may exclude treatment of family
      members from doctors' insurance cover. Think very carefully before you prescribe
      for family and friends. It is only considered ethically and professionally
      appropriate to prescribe in exceptional circumstances, and there are potential
      risks to you and your family member or friend if you do. 

PMID- 27041800
TI  - Exciting things happening in the digital space.

PMID- 27041801
TI  - Anal fissure.
AB  - An anal fissure is a common, mostly benign, condition that can be acute or
      chronic. The diagnosis is usually made on history and physical examination, but
      further investigations are sometimes necessary. Primary fissures are usually
      benign and located in the posterior or anterior position. Secondary fissures are
      lateral or multiple and often indicate a more serious underlying pathology. The
      management of primary anal fissures is generally non-operative and includes
      increased dietary fibre, sitz baths, topical ointments and botulinum toxin
      injections. If these treatments are ineffective the patient will need a surgical
      referral. Secondary anal fissures require further investigation.
      Multidisciplinary management is preferable and is essential in the case of
      malignancy. 

PMID- 27041802
TI  - Management of digoxin toxicity.
AB  - Digoxin toxicity can emerge during long-term therapy as well as after an
      overdose. It can occur even when the serum digoxin concentration is within the
      therapeutic range. Toxicity causes anorexia, nausea, vomiting and neurological
      symptoms. It can also trigger fatal arrhythmias. There is a range of indications
      for using digoxin-specific antibody fragments. The amount ingested and serum
      digoxin concentration help to determine the dose required, but are not essential.
      Digoxin-specific antibody fragments are safe and effective in severe toxicity.
      Monitoring should continue after treatment because of the small risk of rebound
      toxicity. Restarting therapy should take into account the indication for digoxin
      and any reasons why the concentration became toxic. 

PMID- 27041803
TI  - Prescribing for patients on dialysis.
AB  - The pharmacokinetics of a drug may be altered in patients with renal impairment
      who require dialysis. Some drugs are contraindicated. The drug's clearance and
      therapeutic index determine if a dose adjustment is needed. A lower dose or less
      frequent dosing may be required. Consult a reference source or the patient's
      nephrologist before prescribing. Start at a low dose and increase gradually. If
      possible give once-daily drugs after dialysis. 

PMID- 27041804
TI  - Lurasidone.

PMID- 27041805
TI  - Scientometric Analysis of the Journals of the Academy of Medical Sciences in
      Bosnia and Herzegovina.
AB  - INTRODUCTION: Currently in Bosnia and Herzegovina there are 25 journals in the
      field of biomedicine, 6 of them are indexed in Medline/PubMed base (Medical
      Archives, Materia Socio-Medica, Acta Informatica Medica, Acta Medica Academica,
      Bosnian Journal of Basic Medical Sciences (BJBMS) and Medical Glasnik), and one
      (BJBMS) is indexed in Science Citation Index Expanded (SCIE)/Web of Science base.
      AIM: The aim of this study was to show the scope of work of the journals that
      were published by Academy of Medical Sciences of Bosnia and Herzegovina - Medical
      Archives, Materia Socio-Medica and Acta Informatica Medica. MATERIAL AND METHODS:
      The research presents a meta-analysis of three journals, or their issues, during
      the calendar year 2015 (retrospective and descriptive character). RESULTS: During
      2015 calendar year a total of 286 articles were published (in Medical Archives
      104 (36.3%), in Materia Socio-Medica 99 (34.6%), and in Acta Informatica Medica
      83 (29%)). Original articles are present in the highest number in all three
      journals (in Medical Archives 80.7%, in Materia Socio Medica 77.7%, and in Acta
      Informatica Medica 68.6%). In Medical Archives, 90.3% of the articles were
      related to the field of clinical medicine. In Materia Socio-Medica, the domain of
      clinical medicine and public health was the most represented. Preclinical areas
      are most frequent in Acta Informatica Medica. The period of 50-60 days for a
      decision on the admission of article is most common in all three journals, with
      trend of shortening of that period. Articles came from 19 countries, mostly from
      Bosnia and Herzegovina, then from Iran, Kosovo, Saudi Arabia and Greece.
      CONCLUSION: In Medical Archives original articles in the field of clinical
      medicine (usually internal and surgical disciplines) are most often present, and
      that is the case in last four years. The number of articles in Materia Socio
      Medica and Acta Informatica Medica is growing from year to year. In Materia Socio
      Medica there is a trend of growth of articles in the field of public health,
      while the most common articles in Acta Informatica Medica are about medical
      informatics.

PMID- 27041806
TI  - Interventional Radiologists: a Necessary Evaluation of Technical, Protective and
      Technological Operation.
AB  - BACKGROUND AND PURPOSE: To present the results of occupational radiation doses
      investigated through a Hospitals of Mazandaran Medical Science Universities in
      north of Iran. Radiology unit has an important role in diagnosis of many
      disorders with providing suitable and high quality pictures. A good picture was
      provided using correct technical criteria and suitable circumstance of patient.
      Finally, operation and knowledge of radiology personnel directly has a primary
      role in determining quality of radiography. MATERIALS AND METHODS: This study was
      done in order to determine personnel operation in the units of hospitals
      radiologist related to University of Mazandaran Medical Science. Data collection
      tools are made of a researcher check list that was used after obtaining suitable
      letter and validity indexes. All of the 73 personnel of radiology unit related to
      Mazandaran Medical Science were studied. 35 operations (in technical, protective
      and technological fields) of any personnel, in three distinct shifts were
      observed and recorded. All of them were tested regarding these three fields with
      a total of 40 questions. RESULTS: The total scores received from personnel in
      technical part in the morning, evening and night shift were 66.4, 53.9 and 60.2
      percent respectively. Received scores from personnel in the protective fields
      were 68.1, 59.5 and 60.2 percent. Moreover, received scores from personnel in the
      technological operation fields were 47.8, 39.95 and 43.65 percent respectively.
      Comparison of these three scores in technical, protective and technological
      operation fields showed a meaningful difference (p<0.05). CONCLUSION: The overall
      quality of personnel operations were nearly desirable and in need of continuous
      education, supervision and evaluation. Emphasizing protection to beams,
      accessibility of necessary tools, continuous supervision regarding the usage of
      these equipments and respecting the other security points have an important role
      in decreasing patients absorbed doses.

PMID- 27041807
TI  - Defining the Modalities of Intravenous Contrast Application During the
      Diagnostics of Hepatic Metastases with Computerized Tomography.
AB  - INTRODUCTION: The liver is the biggest human abdominal parenchymal organ; it
      weights approximately 1500 grams and is located in the right hypochondrium, under
      the diaphragm. Liver is able to perform multiple functions also by means of the
      rich dual vascularization: hepatic arterial system and the portal vein system,
      between which exists a short circuit (shunt) and free mixture inside the
      sinusoid, whilst the two flows drain in the same vein system. The discovery of CT
      and its application in practice fundamentally changes the importance of
      diagnostic methods for hepatobiliary lesions. PATIENTS AND METHODS: During a 4
      year period, 984 patients suspected with liver or biliary tract disease were
      explored with CT. 117 of these patients were analyzed with liver metastases.
      Examinations of the liver was performed in dorsal decubitus and in absolute apnea
      with spiral movement of the table and in denominations of 1and 5 mm. Siemens MSCT
      64 and 6 tier apparatuses enable short scanning time with almost immediate
      reconstruction, which offers all the necessary elements required for carrying out
      certain protocols. RESULTS: The average density of metastatic lesions is about 20
      HU smaller than normal liver parenchyma. Metastasis with necrosis are more
      hypodense (30-50 HU smaller than normal liver parenchyma), whilst necrotic
      metastases with smaller dimensions are almost isodense with normal parenchyma.
      However, metastases with diameter between 4 to 6 cm are completely isodense and
      will remain so even after the application of I.V. contrast. The average more
      frequent size according to most authors, as well as according to our material
      (148 patients or 90%) was 2-3 cm in transversal diameter.

PMID- 27041808
TI  - Developing a Fuzzy Expert System to Predict the Risk of Neonatal Death.
AB  - INTRODUCTION: This study aims at developing a fuzzy expert system to predict the
      possibility of neonatal death. MATERIALS AND METHODS: A questionnaire was given
      to Iranian neonatologists and the more important factors were identified based on
      their answers. Then, a computing model was designed considering the fuzziness of
      variables having the highest neonatal mortality risk. The inference engine used
      was Mamdani's method and the output was the risk of neonatal death given as a
      percentage. To validate the designed system, neonates' medical records real data
      at a Tehran hospital were used. MATLAB software was applied to build the model,
      and user interface was developed by C# programming in Visual Studio platform as
      bilingual (English and Farsi user interface). RESULTS: According to the results,
      the accuracy, sensitivity, and specificity of the model were 90%, 83% and 97%,
      respectively. CONCLUSION: The designed fuzzy expert system for neonatal death
      prediction showed good accuracy as well as proper specificity, and could be
      utilized in general hospitals as a clinical decision support tool.

PMID- 27041809
TI  - Comparing Smoothing Techniques for Fitting the Nonlinear Effect of Covariate in
      Cox Models.
AB  - BACKGROUND AND OBJECTIVE: Cox model is a popular model in survival analysis,
      which assumes linearity of the covariate on the log hazard function, While
      continuous covariates can affect the hazard through more complicated nonlinear
      functional forms and therefore, Cox models with continuous covariates are prone
      to misspecification due to not fitting the correct functional form for continuous
      covariates. In this study, a smooth nonlinear covariate effect would be
      approximated by different spline functions. MATERIAL AND METHODS: We applied
      three flexible nonparametric smoothing techniques for nonlinear covariate effect
      in the Cox models: penalized splines, restricted cubic splines and natural
      splines. Akaike information criterion (AIC) and degrees of freedom were used to
      smoothing parameter selection in penalized splines model. The ability of
      nonparametric methods was evaluated to recover the true functional form of
      linear, quadratic and nonlinear functions, using different simulated sample
      sizes. Data analysis was carried out using R 2.11.0 software and significant
      levels were considered 0.05. RESULTS: Based on AIC, the penalized spline method
      had consistently lower mean square error compared to others to selection of
      smoothed parameter. The same result was obtained with real data. CONCLUSION:
      Penalized spline smoothing method, with AIC to smoothing parameter selection, was
      more accurate in evaluate of relation between covariate and log hazard function
      than other methods.

PMID- 27041810
TI  - Evaluating Usability of Radiology Information Systems in Hospitals of Tabriz
      University of Medical Sciences.
AB  - INTRODUCTION AND PURPOSE: Radiology information system (RIS) in order to reduce
      workload and improve the quality of services must be well-designed. Heuristic
      evaluation is one of the methods that understand usability problems with the
      least time, cost and resources. The aim of present study is to evaluate the
      usability of RISs in hospitals. RESEARCH METHOD: This is a cross-sectional
      descriptive study (2015) that uses heuristic evaluation method to evaluate the
      usability of RIS used in 3 hospitals of Tabriz city. The data are collected using
      a standard checklist based on 13 principles of Nielsen Heuristic evaluation
      method. Usability of RISs was investigated based on the number of components
      observed from Nielsen principles and problems of usability based on the number of
      non-observed components as well as non-existent or unrecognizable components.
      RESULTS: by evaluation of RISs in each of the hospitals 1, 2 and 3, total numbers
      of observed components were obtained as 173, 202 and 196, respectively. It was
      concluded that the usability of RISs in the studied population, on average and
      with observing 190 components of the 291 components related to the 13 principles
      of Nielsen is 65.41 %. Furthermore, problems of usability were obtained as
      26.35%. DISCUSSION AND CONCLUSION: The established and visible nature of some
      components such as response time of application, visual feedbacks, colors, view
      and design and arrangement of software objects cause more attention to these
      components as principal components in designing UI software. Also, incorrect
      analysis before system design leads to a lack of attention to secondary needs
      like Help software and security issues.

PMID- 27041811
TI  - Factors Affecting Successful Implementation of Hospital Information Systems.
AB  - BACKGROUND: Today, the use of information systems in health environments, like
      any other fields, is necessary and organizational managers are convinced to use
      these systems. However, managers' satisfaction is not the only factor in
      successfully implementing these systems and failed information technology
      projects (IT) are reported despite the consent of the directors. Therefore, this
      study aims to determine the factors affecting the successful implementation of a
      hospital information system. METHODS: The study was carried out as a descriptive
      method in 20 clinical hospitals that the hospital information system (HIS) was
      conducted in them. The clinical and paraclinical users of mentioned hospitals are
      the study group. 400 people were chosen as samples in scientific method and the
      data was collected using a questionnaire consisted of three main human,
      managerial and organizational, and technological factors, by questionnaire and
      interview. Then the data was scored in Likert scale (score of 1 to 5) and were
      analyzed using the SPSS software. RESULTS: About 75 percent of the population
      were female, with average work experience of 10 years and the mean age was 30
      years. The human factors affecting the success of hospital information system
      implementation achieved the mean score of 3.5, both organizational and managerial
      factors 2.9 and technological factors the mean of 3. CONCLUSION: Human factors
      including computer skills, perceiving usefulness and perceiving the ease of a
      hospital information system use are more effective on the acceptance and
      successful implementation of hospital information systems; then the technological
      factors play a greater role. It is recommended that for the successful
      implementation of hospital information systems, most of these factors to be
      considered.

PMID- 27041812
TI  - Comparative Investigation of Health Literacy Level of Cardiovascular Patients
      Hospitalized in Private and Educational Hospitals of Kerman City, Iran.
AB  - INTRODUCTION: literacy involves a complex set of abilities to understand and use
      symbolic systems of a culture for personal development and social development in
      a diverse set of skills required as an adult to exercise behavior are considered
      in society. OBJECTIVES: The aim of this study was to evaluate Comparative
      investigation of health literacy level of cardiovascular patients hospitalized in
      private and public educational hospitals of Kerman city. METHODS: This study used
      survey methods, analytical and cross-sectional manner. Data was collected through
      questionnaires distributed among 200 patients of cardiovascular-hospitalization
      took place in the city of Kerman. To analyze the data in the description of the
      mean, standard deviation and frequency distribution tables and the level of
      analysis to determine the relationship between gender and marital status of
      health literacy test or nonparametric test Mann-Whitney T-Test and, for the
      relationship between group employment and residence, a one-way analysis of
      variance or Kruskal-Wallis test, to evaluate the relationship between age and
      income, Pearson and Spearman correlation to investigate the relationship between
      level of education and health literacy of SPPS software version 21 was used.
      RESULTS: The results showed that 10% of patients at educational hospitals in
      Kerman adequate health literacy, and 48% of patients in private hospitals had
      adequate health literacy. As a result, there is a significant difference of
      health literacy between the two types of hospital (p-value <0/0001). CONCLUSIONS:
      The results showed that most patients had inadequate and border health literacy
      have been. Health plans, preparation of simple educational system and
      understanding, spending more time and have a discussion with the lower speed In
      connection with the patient's doctor and medical staff, Including ways to help
      patients with low health literacy and improve their health literacy is.

PMID- 27041813
TI  - ELISA Test for Analyzing of Incidence of Type 1 Diabetes Autoantibodies (GAD and
      IA2) in Children and Adolescents.
AB  - INTRODUCTION: Anti GAD (antibodies on glutamic acid decarboxylase) and anti-IA2
      antibodies (against tyrosine phosphatase), today, have their place and importance
      in diagnosis and prognosis of Type 1 diabetes. Huge number of patients with
      diabetes mellitus type 1 have these antibodies. Insulin antibodies are of
      critical importance in diagnosis of diabetes mellitus type 1 for pediatric
      population. MATERIALS AND METHODS: During 2014, the samples of 80 patients from
      Clinical Center University Sarajevo (CCUS) Pediatrics clinic's, Endocrinology
      department were analyzed on anti-GAD and IA2 antibodies. The samples of serums of
      all patients were analyzed with ELISA tests using Anti GAD ELISA (IgG) kites from
      EUROIMMUN company. These are quantitative in vitro tests for human antibodies
      against decarboxylase of glutamine acid (GAD) and IA2, in serum or EDTA plasm.
      RESULTS: During the period of one year, in CCUS's Organizational unit, Institute
      for Clinical Immunology, 80 samples of patients with anti GAD and IA2 antibodies
      were analyzed. Out of total number of samples, 41 were male patients, or 51% and
      39 female, or 49%. The youngest patient was born in 2012, and the oldest in 1993.
      Age average was represented by the patients born in 2001. Share of positive
      results for IA2 antibodies and GAD antibodies was 37% for IA2 antibodies, and 63%
      for GAD antibodies. DISCUSSION: During an autoimmune - mediated Diabetes mellitus
      type 1 leads to T-cell mediated destruction of beta cells of pancreatic islets,
      reduced production of insulin and glucose metabolism. Studies have shown that
      these bodies are the most intense single marker for identifying persons with
      increased risk for diabetes development.

PMID- 27041814
TI  - Social and Psychological Effects of the Internet Use.
AB  - BACKGROUND AND AIMS: Over the past two decades there was an upsurge of the use of
      Internet in human life. With this continuous development, Internet users are able
      to communicate with any part of the globe, to shop online, to use it as a mean of
      education, to work remotely and to conduct financial transactions. Unfortunately,
      this rapid development of the Internet has a detrimental impact in our life,
      which leads to various phenomena such as cyber bullying, cyber porn, cyber
      suicide, Internet addiction, social isolation, cyber racism etc. The main purpose
      of this paper is to record and analyze all these social and psychological effects
      that appears to users due to the extensive use of the Internet. MATERIALS AND
      METHODS: This review study was a thorough search of bibliography data conducted
      through Internet and library research studies. Key words were extracted from
      search engines and data bases including Google, Yahoo, Scholar Google, PubMed.
      FINDINGS: The findings of this study showed that the Internet offers a quick
      access to information and facilitates communication however; it is quite
      dangerous, especially for young users. For this reason, users should be aware of
      it and face critically any information that is handed from the website.

PMID- 27041815
TI  - Laparoscopic Management of Adhesive Small Bowel Obstruction.
AB  - INTRODUCTION: Adhesions are the reason for bowel obstruction in 80% of the cases.
      In well selected patients the adhesive ileus laparoscopic treatment has multiple
      advantages which include the shorter hospitalization period, earlier food taking,
      and less postoperative morbidity rate. CASE REPORT: Here we have a patient in the
      age of 35 hospitalized at the clinic due to occlusive symptoms. Two years before
      an opened appendectomy had been performed on him. He underwent the treatment of
      exploration laparoscopy and laparoscopic adhesiolysis. Dilated small bowel loops
      connected with the anterior abdominal wall in the ileocecal region by adhesions
      were found intraoperatively and then resected harmonically with scalpel. One
      strangulation around which a small bowel loop was wrapped around was found and
      dissected. Postoperative course was normal.

PMID- 27041816
TI  - Successful Evaluation of Biphasic T-wave of Wellens Syndrome in the Emergency
      Department.
AB  - INTRODUCTION: Wellens Syndrome (WS) is a condition characterized by typical
      changes in ECG, which are biphasic T-wave inversions (less common) or symmetric
      and deeply inverted T waves (including 75%) in lead V2-V3 chest derivations. WS
      is considered important because it has not only diagnostic value but also
      prognostic value. CASE REPORT: A 52-year-old male patient without cardiovascular
      disease or risk factors was admitted to the emergency department (ED) suffering
      with chest pain and syncope, just after having been involved in a discussion at
      work. Chest pain was radiating to the left arm and was not precipitated by
      exertion. Shortness of breath was not accompanied by angina. The patient
      underwent cardiac catheterization at Department of Cardiology. Stents were
      positioned in both LADA and a severe lesion in the left main coronary artery. The
      patient was discharged two days following catheterization, due to no chest pain
      and hemodynamic instability during the hospitalization. The patient has approved
      the inform consent for to be used for this case report.

PMID- 27041817
TI  - Foramen Magnum Meningioma: a Case Report and Review of Literature.
AB  - INTRODUCTION: Meningiomas are slow-growing benign tumors that arise at any
      location where arachnoid cells reside. Although meningiomas account for a sizable
      proportion of all primary intracranial neoplasms (14.3-19%), only 1.8 to 3.2%
      arise at the foramen magnum. Their indolent development at the craniocervical
      junction makes clinical diagnosis complex and often leads to a long interval
      between onset of symptoms and diagnosis. CASE REPORT: We report a case of a 79
      year-old male patient, presented with ataxia and sense of threatening fainting
      during verticalization. Magnetic resonance imaging revealed the presence of
      meningioma in the right side of craniospinal junction.

PMID- 27041818
TI  - Complex mountain terrain and disturbance history drive variation in forest
      aboveground live carbon density in the western Oregon Cascades, USA.
AB  - Forest carbon (C) density varies tremendously across space due to the inherent
      heterogeneity of forest ecosystems. Variation of forest C density is especially
      pronounced in mountainous terrain, where environmental gradients are compressed
      and vary at multiple spatial scales. Additionally, the influence of environmental
      gradients may vary with forest age and developmental stage, an important
      consideration as forest landscapes often have a diversity of stand ages from past
      management and other disturbance agents. Quantifying forest C density and its
      underlying environmental determinants in mountain terrain has remained
      challenging because many available data sources lack the spatial grain and
      ecological resolution needed at both stand and landscape scales. The objective of
      this study was to determine if environmental factors influencing aboveground live
      carbon (ALC) density differed between young versus old forests. We integrated
      aerial light detection and ranging (lidar) data with 702 field plots to map
      forest ALC density at a grain of 25 m across the H.J. Andrews Experimental
      Forest, a 6369 ha watershed in the Cascade Mountains of Oregon, USA. We used
      linear regressions, random forest ensemble learning (RF) and sequential
      autoregressive modeling (SAR) to reveal how mapped forest ALC density was related
      to climate, topography, soils, and past disturbance history (timber harvesting
      and wildfires). ALC increased with stand age in young managed forests, with much
      greater variation of ALC in relation to years since wildfire in old unmanaged
      forests. Timber harvesting was the most important driver of ALC across the entire
      watershed, despite occurring on only 23% of the landscape. More variation in
      forest ALC density was explained in models of young managed forests than in
      models of old unmanaged forests. Besides stand age, ALC density in young managed
      forests was driven by factors influencing site productivity, whereas variation in
      ALC density in old unmanaged forests was also affected by finer scale topographic
      conditions associated with sheltered sites. Past wildfires only had a small
      influence on current ALC density, which may be a result of long times since fire
      and/or prevalence of non-stand replacing fire. Our results indicate that forest
      ALC density depends on a suite of multi-scale environmental drivers mediated by
      complex mountain topography, and that these relationships are dependent on stand
      age. The high and context-dependent spatial variability of forest ALC density has
      implications for quantifying forest carbon stores, establishing upper bounds of
      potential carbon sequestration, and scaling field data to landscape and regional
      scales.

PMID- 27041819
TI  - Comparative Study of the Thermal Conductivity of Solid Biomass Fuels.
AB  - The thermal conductivity of solid biomass fuels is useful information in the
      investigation of biomass combustion behavior and the development of modeling
      especially in the context of large scale power generation. There are little
      published data on the thermal conductivity of certain types of biomass such as
      wheat straw, miscanthus, and torrefied woods. Much published data on wood is in
      the context of bulk materials. A method for determining the thermal
      conductivities of small particles of biomass fuels has been developed using a
      custom built test apparatus. Fourteen different samples of various solid biomass
      fuel were processed to form a homogenized pellet for analysis. The thermal
      conductivities of the pelletized materials were determined and compared against
      each other and to existing data.

PMID- 27041820
TI  - Drug-Initiated Synthesis of Polymer Prodrugs: Combining Simplicity and Efficacy
      in Drug Delivery.
AB  - In the field of nanomedicine, the global trend over the past few years has been
      toward the design of highly sophisticated drug delivery systems with active
      targeting and/or imaging capabilities, as well as responsiveness to various
      stimuli to increase their therapeutic efficacy. However, providing sophistication
      generally increases complexity that could be detrimental in regards to potential
      pharmaceutical development. An emerging concept to design efficient yet simple
      drug delivery systems, termed the "drug-initiated" method, consists of growing
      short polymer chains from drugs in a controlled fashion to yield well-defined
      drug-polymer prodrugs. These materials are obtained in a reduced amount of
      synthetic steps and can be self-assembled into polymer prodrug nanoparticles, be
      incorporated into lipid nanocarriers or be used as water-soluble polymer
      prodrugs. This Perspective article will capture the recent achievements from the
      "drug-initiated" method and highlight the great biomedical potential of these
      materials.

PMID- 27041821
TI  - Structural Prediction in Aphasia: Evidence from either.
AB  - Young neurotypical adults engage in prediction during language comprehension
      (e.g., Altmann & Kamide, 1999; Staub & Clifton, 2006; Yoshida, Dickey & Sturt,
      2013). The role of prediction in aphasic comprehension is less clear. Some
      evidence suggests that lexical prediction may be spared in aphasia (Dickey et
      al., 2014; Love & Webb, 1977; cf. Mack et al, 2013), and there is even indication
      that structural prediction may be spared in some people with aphasia (PWA; e.g.
      Hanne, Burchert, De Bleser, & Vashishth, 2015). The current self-paced reading
      experiment manipulated the presence of either to examine structural prediction
      among PWA and a set of similar-aged neurotypical control participants. Consistent
      with intact structural prediction for both groups of participants, when either
      preceded a disjunction, reading times were faster on the or and second disjunct
      (cf. Staub & Clifton, 2006). For neurotypical controls, this effect of the
      presence vs. absence of either shrank reliably as more experimental items were
      encountered, whereas for PWA there was a non-significant trend for it to grow as
      more experimental items were encountered. These findings indicate that PWA and
      older neurotypical individuals can use a lexical cue to predict the structural
      form of upcoming material during comprehension, but that on-line adaptation to
      patterns in the local context may be different for the two groups.

PMID- 27041822
TI  - Socialization in the Context of Risk and Psychopathology: Maternal Emotion
      Socialization in Children of Incarcerated Mothers.
AB  - Children of incarcerated mothers are at increased risk for psychological, social,
      and emotional maladaptation. This research investigates whether perceived
      maternal socialization of sadness and anger may moderate these outcomes in a
      sample of 154 children (53.9% boys, 61.7% Black, M age = 9.38, range: 6 - 12),
      their 118 mothers (64.1% Black), and 118 caregivers (74.8% female, 61.9%
      grandparents, 63.2% Black). Using mother, caregiver, and child report, seven
      maternal socialization strategies were assessed in their interaction with
      incarceration-specific risk experiences predicting children's adjustment. For
      sadness socialization, the results indicated that among children reporting
      maternal emotion-focused responses, incarceration-specific risk predicted
      increases in psychological problems, depressive symptoms, increased emotional
      lability, and poorer emotion regulation. For children who perceived a problem
      focused response, incarceration-specific risk did not predict outcomes. There
      were no significant interactions with incarceration-specific risk and perceived
      maternal anger socialization strategies. These results indicate a critical need
      to examine how socialization processes may operate differently for children
      raised in atypical socializing contexts.

PMID- 27041823
TI  - Smoking Functions as a Negative Regulator of IGF1 and Impairs Adipokine Network
      in Patients with Rheumatoid Arthritis.
AB  - OBJECTIVES: Smoking is pathogenic for rheumatoid arthritis (RA) being tightly
      connected to the genetic and serological risk factors for this disease. This
      study aims to understand connections between cigarette smoking and serum levels
      of IGF1 and adipokines in RA. METHODS: Serum levels of IGF1 and adipokines
      leptin, adiponectin, resistin, and visfatin were measured in two independent
      cohorts of RA patients from Gothenburg (n = 350) and Leiden (n = 193). An
      association of these parameters with smoking was tested in a direct comparison
      and proved by bivariate correlation analysis. The obtained associations were
      further tested in multivariate regression models where the confounders (age,
      gender, disease duration, and BMI) were controlled. RESULTS: The smokers had
      significantly lower serum levels of IGF1, adiponectin, and leptin compared to
      never smokers. In regression analysis, smoking and low leptin, but not
      adiponectin, were associated and predicted low IGF1. Additionally, high disease
      activity and high BMI increased the probability of low leptin. CONCLUSIONS: The
      study indicates cigarette smoking as an important cause of a relative IGF1 and
      leptin deficiency in RA patients. This novel association between smoking and
      hypoleptinemia may be of importance for long-term prognosis of RA and for
      prediction of comorbidities.

PMID- 27041824
TI  - The Role of Protein Arginine Methyltransferases in Inflammatory Responses.
AB  - Protein arginine methyltransferases (PRMTs) mediate the methylation of a number
      of protein substrates of arginine residues and serve critical functions in many
      cellular responses, including cancer development, progression, and
      aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are
      nine members of the PRMT family, which are divided into 4 types (types I-IV).
      Although most PRMTs do not require posttranslational modification (PTM) to be
      activated, fine-tuning modifications, such as interactions between cofactor
      proteins, subcellular compartmentalization, and regulation of RNA, via micro
      RNAs, seem to be required. Inflammation is an essential defense reaction of the
      body to eliminate harmful stimuli, including damaged cells, irritants, or
      pathogens. However, chronic inflammation can eventually cause several types of
      diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and
      periodontitis. Therefore, inflammation responses should be well modulated. In
      this review, we briefly discuss the role of PRMTs in the control of inflammation.
      More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and
      PRMT6) in modulating inflammation responses, particularly in terms of modulating
      the transcriptional factors or cofactors related to inflammation. Based on the
      regulatory roles known so far, we propose that PRMTs should be considered one of
      the target molecule groups that modulate inflammatory responses. 

PMID- 27041825
TI  - Inhibiting HMGB1 with Glycyrrhizic Acid Protects Brain Injury after DAI via Its
      Anti-Inflammatory Effect.
AB  - High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine
      like activity, is involved in several neurological diseases by mediating
      inflammatory response. In this study, a lateral head rotation device was used to
      establish a rat diffuse axonal injury (DAI) model. The dynamic expression of
      HMGB1, apoptosis-associated proteins, and proinflammatory cytokines were detected
      by Western blot, and neuronal apoptosis was observed by TUNEL staining. The
      extracellular release of HMGB1 and the accumulation of beta-APP were observed by
      immunofluorescence and immunohistochemistry, respectively. The brain injury was
      indicated by modified neurological severity score (mNSS), brain water content
      (BWC), and the extravasation of Evans blue. We showed that HMGB1 level obviously
      decreased within 48 h after DAI, accompanied by neuronal apoptosis, the
      activation of caspases 3 and 9, and the phosphorylation of BCL-2. Inhibiting
      HMGB1 with glycyrrhizic acid (GL) can suppress the activation of apoptosis
      associated proteins and inhibit the expression of proinflammatory cytokines,
      which ameliorated motor and cognitive deficits, reduced neuronal apoptosis, and
      protected the integrity of blood brain barrier (BBB) and axonal injury after
      experimental DAI in rats. Thus, HMGB1 may be involved in the inflammatory
      response after DAI, and inhibition of HMGB1 release with GL can notably alleviate
      the brain injury after DAI. 

PMID- 27041827
TI  - The art and science of Bibliotherapy... Bibliology... Bibliography???

PMID- 27041826
TI  - Cytokines and Effector/Regulatory Cells Characterization in the Physiopathology
      of Cutaneous Lupus Erythematous: A Cross-Sectional Study.
AB  - We compared the presence of diverse cytokines and regulatory T and B cells in
      skin biopsies of discoid lupus erythematosus (DLE) and subacute cutaneous lupus
      erythematosus (SCLE). We included 19 patients with DLE, 13 with SCLE, 8 healthy
      controls, and 5 patients with hypertrophic scars. We assessed the CLASI activity
      score. To determine IL-22-producing cells and the subpopulation of CD4(+)/IL
      17A(+)-, CD4(+)/IL-4(+)-, and CD4(+)/IFN-gamma (+)-expressing T cells,
      CD123(+)/IDO(+) pDCs, CD25(+)/Foxp3(+) Tregs, and CD20(+)/IL-10(+)-producing B
      cells, an immunostaining procedure was performed. Also intracellular IL-22, IL
      17, IL-4, IFN-gamma, and Foxp3 in CD4 T cells, IL-10 in B cells, and IDO in pDCs
      were analyzed by flow cytometry in peripheral blood. The main cellular
      participation in both lupus groups was IL-17- and IL-22-producing cell responses
      both at skin and at peripheral blood but prevailed in DLE. The CLASI activity
      scores negatively correlated with Th22 subpopulation and positively correlated
      with CD25(+)/Foxp3(+) Treg cells. In conclusion a proinflammatory and regulatory
      imbalance coexists in cutaneous lupus, both responses being more intense in DLE. 

PMID- 27041828
TI  - Learning Curve.

PMID- 27041829
TI  - Capillary hemangioma or pyogenic granuloma.

PMID- 27041831
TI  - A finite element study to determine the occurrence of abfraction and displacement
      due to various occlusal forces and with different alveolar bone height.
AB  - BACKGROUND: Noncarious cervical lesions (NCCLs) are rarely described in the
      periodontal literature, perhaps because no direct link between NCCLs and
      periodontal lesions has been demonstrated. AIM: The aim of this study is to
      determine the stress and displacement produced in the tooth at different bone
      levels under different occlusal load using finite element model (FEM) study.
      MATERIALS AND METHODS: Four FEMs of maxillary incisor were designed consisting of
      the tooth, pulp, periodontal ligament, and alveolar bone at the various level of
      bone height (25%, 50%, and 75%). Different occlusal load (5 kg, 15 kg, 24 kg, and
      29 kg) at an angle of 50 degrees  to the long axis of the tooth was applied on
      the palatal surface at the level of middle third of the crown. All the models
      were assumed to be isotropic, linear and elastic, and the analysis was performed
      on a Pentium IV processor computer using the ANSYS software. RESULTS: The maximum
      stress in the tooth was seen in the cervical region and to a greater extent at
      the apex for all models. The maximum tooth displacement for all the occlusal
      loads applied in this study was at the incisal edge with the minimum tooth
      displacement at the cervical third of the root which shifted apically with the
      reduction of alveolar bone support. CONCLUSION: The cumulative effect of
      increased stress and displacement at the cervical region of the tooth would
      result in abfraction as the age advances along with other wasting diseases.

PMID- 27041830
TI  - Implant fractures: Rare but not exceptional.
AB  - Fabrication of dentures aided with implants has become a preferred treatment
      option for rehabilitation of completely and partially edentulous patients when
      durability is concerned. Simulation to natural teeth in terms of esthetics and to
      a greater extent in function can be considered as key elements in the raise of
      implant dentistry worldwide. Despite its high success rate, therapy with
      osseointegrated dental implants is not free of complications. Implant failure can
      occur for other reasons, with implant fracture being one of the major reasons for
      late failure. Although the incidence of implant fractures may be low, it
      invariably effects the patient and also clinician. Thus, sound evidence based
      knowledge of cause of fracture is mandatory for that careful treatment that can
      reduce the incidence of fracture helping in a better treatment plan. The aim of
      this review is to enlighten the various causes of implant fracture. 

PMID- 27041832
TI  - Identical mitochondrial somatic mutations unique to chronic periodontitis and
      coronary artery disease.
AB  - CONTEXT: The inflammatory processes involved in chronic periodontitis and
      coronary artery diseases (CADs) are similar and produce reactive oxygen species
      that may result in similar somatic mutations in mitochondrial deoxyribonucleic
      acid (mtDNA). AIMS: The aims of the present study were to identify somatic mtDNA
      mutations in periodontal and cardiac tissues from subjects undergoing coronary
      artery bypass surgery and determine what fraction was identical and unique to
      these tissues. SETTINGS AND DESIGN: The study population consisted of 30 chronic
      periodontitis subjects who underwent coronary artery surgery after an angiogram
      had indicated CAD. MATERIALS AND METHODS: Gingival tissue samples were taken from
      the site with deepest probing depth; coronary artery tissue samples were taken
      during the coronary artery bypass grafting procedures, and blood samples were
      drawn during this surgical procedure. These samples were stored under aseptic
      conditions and later transported for mtDNA analysis. STATISTICAL ANALYSIS USED:
      Complete mtDNA sequences were obtained and aligned with the revised Cambridge
      reference sequence (NC_012920) using sequence analysis and auto assembler tools.
      RESULTS: Among the complete mtDNA sequences, a total of 162 variations were
      spread across the whole mitochondrial genome and present only in the coronary
      artery and the gingival tissue samples but not in the blood samples. Among the
      162 variations, 12 were novel and four of the 12 novel variations were found in
      mitochondrial NADH dehydrogenase subunit 5 complex I gene (33.3%). CONCLUSIONS:
      Analysis of mtDNA mutations indicated 162 variants unique to periodontitis and
      CAD. Of these, 12 were novel and may have resulted from destructive oxidative
      forces common to these two diseases.

PMID- 27041833
TI  - Profilometric analysis of root surfaces after using various polishing agents.
AB  - BACKGROUND: Polishing is an important step in oral prophylaxis procedure which
      retards further accumulation of plaque on the root surfaces. Though polishing was
      done with various abrasive particles with different sizes over a long period of
      time, it was never been highlighted to evaluate the ideal polishing material and
      the particle size that would produce the ideal surface smoothness (Ra <0.2 MUm).
      MATERIALS AND METHODS: The present study was carried out on 70 periodontally
      involved, caries-free extracted human teeth from 42 patients. All the teeth were
      collected from the region of incisors, canines, and premolars. In vitro scaling
      and root planing were performed by piezoelectric scaler and Gracey's area
      specific curettes, respectively. All the teeth were grouped at random into
      control and experimental. The collections of abrasive materials were done
      directly from the market, and the different particle sizes were prepared in the
      laboratory. EXPERIMENTATION: The polishing was done at a constant speed of 200
      rpm with cylindrical nylon bristle brush followed by rubber prophy cup. Each
      group belonging to control and experimental was subjected to profilometric study
      for evaluation of surface roughness. RESULTS: Regular polishing abrasives are not
      able to produce the surface smoothness of our desire level (i.e., Ra <0.2 MUm),
      which can be achieved only by submicron-sized particles. CONCLUSION: Regular size
      polishing particles available in the market (>5 MUm) are not able to produce the
      surface smoothness <0.2 MUm. Only, submicron sized particles are able to produce
      the desired smoothness.

PMID- 27041834
TI  - Paralleling technique for frenectomy and oral hygiene evaluation after
      frenectomy.
AB  - BACKGROUND: High frenum attachment is a very common problem in the population.
      Various conventional techniques are available which has certain disadvantages; in
      addition to that high frenum also hinders oral hygiene maintenance. This study
      aims to evaluate patient's response to two different frenectomy technique, and
      oral hygiene maintenance before and after frenectomy. MATERIALS AND METHODS:
      Twenty patients with high labial frenum were randomly selected from the
      outpatient department. Patients were divided into two groups according to the
      technique used. Each group contained ten patients. One group was treated by
      "conventional scalpel technique" and other group by "new paralleling technique".
      To evaluate patients response, visual analogue scale for pain and speech were
      taken at first postoperative day, 1-week and 1-month. In other part of the study
      the oral hygiene maintenance was evaluated by using plaque and gingival bleeding
      index at baseline before frenectomy, 1-week and 1-month after frenectomy.
      RESULTS: Results showed that new paralleling technique for frenectomy causes less
      postoperative discomfort and also there was significant improvement in the oral
      hygiene maintenance by the patient after frenectomy. CONCLUSION: High maxillary
      frenum causes hindrance in oral hygiene maintenance. Paralleling technique for
      frenectomy causes less discomfort to the patient during healing phase when
      compared with the conventional technique.

PMID- 27041835
TI  - Effect of ozonated oil and chlorhexidine gel on plaque induced gingivitis: A
      randomized control clinical trial.
AB  - BACKGROUND: Several chemotherapeutic agents have been developed to prevent
      gingivitis and its progression into periodontitis. In this present study, the
      efficacy of ozonated oil and chlorhexidine gel was assessed and compared on
      plaque induced gingivitis. AIM: To evaluate the effect of ozonated oil on plaque
      induced gingivitis and to compare its efficacy with chlorhexidine gel. MATERIALS
      AND METHODS: A total of 20 subjects, aged from 18 to 65 years, with plaque
      induced gingivitis were selected from the outpatient Department of
      Periodontology, Government Dental College and Hospital, Aurangabad, for this
      study. They were divided randomly into the test or ozonated oil group (Group I)
      and the control or chlorhexidine gel group (Group II) with 10 subjects in each
      group. Subjects were randomly assigned to massage their gingiva thrice a day for
      3 weeks with ozonated oil (test), and chlorhexidine gel (control). Plaque index
      and gingival index scores were recorded for the 20 subjects at baseline and after
      3 weeks. RESULTS: Ozonated oil (Group I) and chlorhexidine gel (Group II) groups
      showed statistically significant differences with respect to plaque index and
      gingival index, from the baseline to 3 weeks (P < 0.001 in both). But the
      difference between Group I and Group II, at the end of the study period, was not
      statistically significant with respect to the plaque index and gingival index.
      CONCLUSIONS: The ozonated oil and chlorhexidine gel, both can be used as an
      effective agent in maintaining and improving gingival health.

PMID- 27041836
TI  - Evaluation of peri-implant soft tissue and bone levels around early loaded
      implant in restoring single missing tooth: A clinico-radiographic study.
AB  - BACKGROUND: One-stage nonsubmerged protocol which can achieve success rates
      comparable to implants placed in a two-staged submerged procedure also the
      preconditions for periimplant bone regeneration has lead to more refined concepts
      of implant loading. MATERIALS AND METHODS: Twenty sites with single missing tooth
      were included in this study. Clinical parameters included sulcus bleeding index
      (sBI), probing pocket depth (PD), and papilla index (PI) and radiographic
      parameters included crestal bone level were assessed for a period of 9 months.
      RESULTS: The crestal bone loss showed mean value ranging from baseline 0.25 +/-
      0.11 to 0.31 +/- 0.08 at 3 weeks, to 0.67 +/- 0.13 at 3 months, to 0.85 +/- 0.09
      at 6 months, and to 0.88 +/- 0.12 at 9 months. Probing PD, the mean value for
      probing PD at 3 weeks 1.20 +/- 0.83, 3 months 1.60 +/- 1.1, at 6 months 1.40 +/-
      1.14, and at 9 months 1.20 +/- 1.0. sBI, mean value for sBI at 3 weeks 0.00 +/-
      0.00, 3 months 0.3 +/- 0.11, at 6 months 0.09 +/- 0.25, and at 9 months 0.08 +/-
      0.24. PI, showed a significant difference among at different points of time with
      P = 0.000. CONCLUSION: The dental implants showed <1 mm of crestal bone loss at 9
      months follow-up, clinically significant marginal bone loss occurred between the
      time of implant placement and 3 months. Subsequent to that, bone loss observed
      around the implant up to 9 months was minimal. The periimplant soft tissue
      maturity was maintained throughout the study.

PMID- 27041837
TI  - Evaluation of platelet-rich plasma alone or in combination with demineralized
      freeze dried bone allograft in treatment of periodontal infrabony defects: A
      comparative clinical trial.
AB  - AIMS: The use of platelet-rich plasma (PRP) alone in periodontal defects has been
      controversial and inconclusive. Hence, the present study was designed with the
      aim to assess the clinical and radiographic effectiveness of PRP alone in
      infrabony defects. MATERIALS AND METHODS: Thirty infrabony defects were treated
      with either autologous PRP with open flap debridement (OFD) or autologous PRP +
      demineralized freeze dried bone graft (DFDBA) with OFD or OFD alone. Clinical
      parameters recorded were gingival index, plaque index, probing depth (PD),
      clinical attachment level (CAL), and gingival recession (REC). Radiographic
      parameters included defect depth reduction, defect resolution, and crestal bone
      level. All the parameters were recorded at baseline and 12 months
      postoperatively. RESULTS: Mean PD reduction and CAL gain were greater in PRP +
      DFDBA (4.88 +/- 1.12 mm and 4.26 +/- 1.85 mm) and PRP (4.86 +/- 2.12 mm and 4.10
      +/- 1.47 mm) groups than the control group (2.69 +/- 1.37 mm and 1.27 +/- 0.89
      mm). CONCLUSIONS: Within the limits of the study, all the three groups showed
      significant improvement in clinical parameters from baseline to postoperative 12
      months. The amount of defect depth reduction and defect resolution treated with
      PRP alone group were significantly < PRP + DFDBA. The results pertaining to these
      parameters were significantly better than the control group.

PMID- 27041838
TI  - Evaluation of effectiveness of hyaluronic acid in combination with bioresorbable
      membrane (poly lactic acid-poly glycolic acid) for the treatment of infrabony
      defects in humans: A clinical and radiographic study.
AB  - BACKGROUND: The combination of biomaterials, bone graft substitutes along with
      guided tissue regeneration (GTR) has been shown to be an effective modality of
      periodontal regenerative therapy for infrabony defects. Therefore, the present
      randomized controlled clinical study was undertaken to evaluate the effectiveness
      of hyaluronic acid (HA) in combination with bioresorbable membrane for the
      treatment of human infrabony defects. MATERIALS AND METHODS: Twenty four
      infrabony defects in 20 systemically healthy patients were randomly assigned to
      test (HA in combination with bioresorbable membrane) and control (bioresorbable
      membrane alone) treatment groups. Probing pocket depth (PPD), relative attachment
      level, and relative gingival margin level were measured with a computerized
      Florida disc probe at baseline and at 6 months follow-up. Radiographic
      measurements were also evaluated at baseline and at 6 months of postsurgery.
      RESULTS: At 6 months, the mean reduction in PPD in test group and control group
      was 4.52 mm and 2.97 mm, respectively. Significantly higher clinical attachment
      level with a gain of 2.20 mm was found in the test group as compared to control
      group. In addition, statistically significant greater reduction of radiographic
      defect depth was observed in the test group. CONCLUSION: Regenerative approach
      using hyaloss in combination with GTR for the treatment of human infrabony
      defects resulted in a significant added benefit in terms of CAL gains, PPD
      reductions and radiographic defect fill, as well as LBG, compared to the GTR
      alone.

PMID- 27041839
TI  - Effect of combination of ethylenediaminetetraacetic acid + tetracycline with
      coronally positioned flap in the treatment of gingival recession: A clinical
      study.
AB  - CONTEXT: Gingival recession is the apical migration of gingival margin results
      from destruction of the connective tissue leading to various esthetic problems.
      Many surgical procedures have been attempted to achieve root coverage that
      include free gingival grafts, pedicle flaps such as semilunar coronally
      repositioned flaps (SCRFs) and guided tissue regeneration. The exposed root
      surface has undergone substantial alterations and may no longer serve as an
      appropriate substrate for cell attachment and fiber development. When the denuded
      root surfaces are treated with biomodifiers following mechanical instrumentation,
      the resulting surface favors both the attachment of fibroblasts and new
      connective tissue attachment. It was then necessary to evaluate the surface
      characteristics of the acid demineralized root surface and its effect on
      periodontal wound healing. AIM: To evaluate the effect of the combination of
      ethylenediaminetetraacetic acid (EDTA) and tetracycline as root bio-modifiers
      along with SCRF for root coverage. SETTINGS AND DESIGN: Twenty subjects were
      randomly assigned into two groups as cases (SCRF + EDTA + tetracycline [TTC]) and
      controls (SCRF). MATERIALS AND METHODS: Twenty-four percentage EDTA and 100 mg/ml
      TTC hydrochloride were used along with semilunar coronally positioned flap. The
      clinical parameters such as recession height, the width of keratinized tissue,
      recession width, clinical attachment level, probing depth, plaque index, and
      gingival index were recorded at baseline, 1 and 3 months. STATISTICAL ANALYSES
      USED: The clinical parameters were compared using post-hoc test and the
      comparison between cases and controls was done using Mann-Whitney U-test.
      RESULTS: No statistical significant difference has been observed between the
      groups. CONCLUSION: It was concluded that no clinical benefit was observed after
      the application of a combination of 100 mg/ml TTC hydrochloride and 24% EDTA on
      the root surface.

PMID- 27041840
TI  - Gingival proliferative lesions in children and adolescents in Brazil: A 15-year
      period cross-sectional study.
AB  - BACKGROUND: Studies assessing the prevalence of oral lesions in children and
      adolescents, particularly in gingiva are scarce in the literature. The aim of the
      study was to describe the distribution of gingival proliferative lesions based on
      clinical and histopathological diagnoses in children and adolescents. MATERIALS
      AND METHODS: A review of clinical charts of children and adolescents aged between
      0 and 18 years old, admitted to the Oral Medicine Outpatient Unit, of
      Universidade Federal do Parana, for 15 years (1994-2009) was performed. RESULTS:
      Six hundred and sixty-nine out of 5,129 patients treated during this period were
      aged between 0 and 18 years old, and 45 of these had gingival lesions. The
      largest number of lesions was observed between 11 and 16 years old. The majority
      of the patients were referred by Curitiba's public health system. Pyogenic
      granuloma was the most frequent lesion (19 = 42.2%), followed by peripheral giant
      cell lesion (11 = 24.4%), gingival fibromatosis (10 = 22.2%), and peripheral
      ossifying fibroma (5 = 11.1%). CONCLUSION: Gingival proliferative lesions can
      show similar clinical characteristics. Appropriate clinical and histopathological
      diagnoses are necessary to guide the healthcare professional to establish the
      adequate treatment and to estimate the risk of recurrence.

PMID- 27041841
TI  - A survey about awareness of periodontal health among the students of professional
      colleges in Dakshina Kannada District.
AB  - INTRODUCTION: Oral health is an important factor in maintaining sound
      psychological and physical health. Association between knowledge and better oral
      health has been well documented. AIM: To assess the oral health awareness and
      knowledge about periodontal diseases among the students of medical, Ayurveda, and
      Engineering Colleges. MATERIALS AND METHODS: A survey was conducted among the
      students of medical, Ayurveda, and engineering colleges. Three hundred students
      were selected using a simple random sampling method and a self-constructed 15
      items questionnaire was distributed to all subjects. Chi-square test was applied
      to individual questions and Kruskal-Wallis test was used to compare overall oral
      health awareness and knowledge about periodontal diseases among the students.
      RESULTS: A substantial lack of oral hygiene understanding and limited knowledge
      of oral hygiene practices even in health professionals and engineering students.
      CONCLUSIONS: Hence, there is an urgent need for comprehensive educational
      programs to promote good oral health and impart education about the correct oral
      hygiene practices at an elementary level.

PMID- 27041842
TI  - Periodontal manifestation of epidermolysis bullosa: Looking through the lens.
AB  - Epidermolysis bullosa (EB) is a genetic disease associated with fragility and
      bullous lesions of the skin and mucous membranes. There are various patterns of
      inheritance and histopathology. The disease is associated with systemic and oral
      manifestations. Treatment of this disease is multidisciplinary and remains only
      palliative till today. The present case report describes periodontal
      manifestations of EB and the treatment plan for the same. 

PMID- 27041843
TI  - Gingival squamous cell carcinoma mimicking as a desquamative lesion.
AB  - Oral squamous cell carcinoma (SCC) is the most frequently encountered neoplasm in
      the oral cavity, which accounts for more than 90% of all cancers. Except for
      carcinoma of the lip vermilion, the most common sites of oral SCC are the tongue
      and floor of mouth, followed at a lower frequency by the soft palate, gingiva,
      and buccal mucosa. Clinically, it may be misdiagnosed because of its variable
      appearances. This case report presents a case of well-differentiated SCC of
      gingiva. A 48-year-old male patient reported to the Department of Periodontology,
      School of Dental Sciences, Karad, with a 1-year history of burning sensation and
      painful lesion on the gingiva from 35 to 37 (mandibular) regions. On clinical
      examination, desquamated gingival lesion was seen with no purulent exudation.
      Clinical characteristics and differential diagnosis indicated the lesion for an
      excisional biopsy. Histopathological examination confirmed the lesion to be a
      well-differentiated SCC. The patient was referred for the treatment consisting of
      surgical excision of the lesion. Since an early diagnosis and treatment was
      possible in this case, it resulted in a good prognosis. In these instances,
      dentist plays an important role in early detection of gingival SCC. 

PMID- 27041844
TI  - The head of a broken toothbrush in the parapharyngeal space: A rare case report.
AB  - While brushing her teeth, the toothbrush of a 4-year-old female child was broken,
      and about 5.4 cm of it including the head was left behind in her mouth. The head
      of the toothbrush penetrated the lateral pharyngeal wall and got strongly
      impacted into the left parapharyngeal space due to the presence of bristles. The
      broken end of the handle was just protruding into the pharynx and was very
      difficult to locate. It led to a life-threatening condition. The head of the
      toothbrush was removed safely by endoscopic approach and the patient recovered
      without any complication. 

PMID- 27041845
TI  - Use of modified lip repositioning technique associated with esthetic crown
      lengthening for treatment of excessive gingival display: A case report of
      multiple etiologies.
AB  - Excessive gingival display during smile can result in compromised esthetics. This
      study aims to report a case of excessive gingival display with multiple
      etiologies treated by means of modified lip repositioning technique associated
      with esthetic crown lengthening. A 23-year-old female patient, with 5-mm gingival
      display during smile caused by altered passive eruption and hypermobility of the
      upper lip, underwent the modified lip repositioning technique associated with
      gingivectomy followed by flap elevation and ostectomy/osteoplasty. Seven months
      after the second procedure, the patient had her esthetic complaint solved
      appearing stable in the observation period. The modified lip repositioning
      technique is an effective procedure employed to reduce gingival display and when
      associated with esthetic clinical crown lengthening, can appropriately treat
      cases of gummy smile. 

PMID- 27041846
TI  - Management of chronic generalized periodontitis using diode laser.
AB  - The aim of this study was to evaluate the effect of a diode laser with
      nonsurgical periodontal therapy on chronic periodontitis. The patient, a 37-year
      old female, with chronic periodontitis reported to the private dental clinic. Her
      health history indicated that she had good general health. The periodontal
      examination included a gingival index and complete periodontal probing depth with
      William's graduated probe. She was treated with 940 nm diode laser and scaling
      and root planning. Assessment was done after 6 months following laser therapy;
      the probing depths improved; gain in clinical attachment levels; no inflammation;
      the tissue tone was good, showing increased stippling. 

PMID- 27041847
TI  - Management of a high risk epileptic patient under conscious sedation: A
      multidisciplinary approach.
AB  - Epilepsy, characterized by the risk of recurrent seizures, is a chronic disease
      that afflicts about 5% of the world's population. The main dental problems
      associated with epileptic patients include gingival hyperplasia, minor oral
      injuries, tooth trauma, and prosthodontic problems, which require the dental
      treatment. Stress and fear are the most common triggering factors for the
      epilepsy in dental chair. Therefore, a more appropriate method of treating such
      epileptic patients may be warranted. Conscious sedation is a technique of
      providing good anesthesia and analgesia to patients, the main advantage of which
      is the patient's rapid return to presentation levels. Midazolam used as a
      sedative agent has anticonvulsant properties. This case report highlights a case
      requiring multiple dental procedures carried out in a high risk epileptic patient
      under conscious sedation. 

PMID- 27041848
TI  - A successfully treated case of severe periodontitis using interdisciplinary
      approach: Report of a case.
AB  - Treatment options for severely misaligned teeth with advanced bone loss are
      limited. We report the management of a case of advanced periodontitis in a
      labially placed extruded maxillary canine. A 24 years old male reported to the
      periodontal clinic to preserve his mobile and misaligned upper left lateral
      incisor. Clinical and radiographic examination revealed advanced attachment loss
      with bone resorption around the affected tooth. The decision was taken to
      reconstruct the lost periodontal tissues in coordination with orthodontic
      intervention to align the tooth in a functionally esthetic position. At the end
      of the combined periodontal and orthodontic treatment, the tooth was preserved
      and was well-aligned in the arch; the patient was satisfied with the treatment
      outcome. It can be concluded that severely misaligned teeth with advanced bone
      loss can be salvaged with a combined and meticulously planned Periodontal
      Orthodontic treatment approach. 

PMID- 27041849
TI  - Idiopathic gingival fibromatosis with asymmetrical presentation and
      electrosurgical management.
AB  - Idiopathic gingival fibromatosis is a rare genetically heterogeneous condition
      characterized by recurrent gingival enlargement without any identifiable cause.
      We report a case of 14-year-old female patient affected with sporadic,
      nonsyndromic, progressive gingival enlargement. It manifested more severely on
      the right side of the mouth with history of recurrence after prior conventional
      surgical excision. Electrosurgical resection of the enlargement was done, and
      overall patient management had a successful outcome along with achieving
      preservation of teeth with poor prognosis in the 2 years follow-up. 

PMID- 27041850
TI  - Crown lengthening procedure following intentional endodontic therapy for
      correction of supra-erupted posterior teeth: Case series with long-term follow
      up.
AB  - CONTEXT: The crown lengthening procedure (CLP) is routinely carried out to
      correct gingival levels and achieve esthetic contours and adequate crown lengths
      for restorative purposes. Though the short-term outcomes have been found to be
      stable, long-term results are not much reported. AIMS: To evaluate the long-term
      stability of the marginal bone levels, gingival levels, and the status of the
      teeth, which underwent endodontic therapy, followed by CLP and final
      restorations. SETTINGS AND DESIGN: Institutional setting, long-term case series.
      MATERIALS AND METHODS: Case records of the patients who underwent CLP and
      endodontic therapy for corrections of the supra-erupted teeth to regain the lost
      interocclusal spaces were retrieved, and the cases with complete set of the
      clinical and radiographs were taken. All the cases were recalled and bone levels
      on the radiographs, bleeding on probing, probing pocket depths, and changes in
      the soft tissue margins were evaluated. STATISTICAL ANALYSIS USED: Descriptive
      analysis. RESULTS: A total of 25 teeth had undergone CLP and endodontic therapy
      and final restorations for a minimum of 24 months. The mean post-restorative
      duration was 50.8 +/- 22.48 months (range 24-96 months). All the teeth were
      functional and asymptomatic with 100% survival. Interdental bone loss of 1 mm,
      probing pockets of 5 mm, and 1 mm buccal recession were observed in 16% of the
      sites. The amount of interocclusal space regained was adequate to restore the
      missing teeth in the opposing arch. CONCLUSIONS: The CLP is a predictive
      procedure for correction of supra-erupted teeth. The survival of the teeth that
      underwent the procedure in the present study was 100% over 24-96 months.

PMID- 27041851
TI  - Identification and Quantification of the Major Constituents in Egyptian Carob
      Extract by Liquid Chromatography-Electrospray Ionization-Tandem Mass
      Spectrometry.
AB  - BACKGROUND: Carob - Ceratonia siliqua L., commonly known as St John's-bread or
      locust bean, family Fabaceae - is one of the most useful native Mediterranean
      trees. There is no data about the chromatography methods performed by high
      performance liquid chromatography (HPLC) for determining polyphenols in Egyptian
      carob pods. OBJECTIVE: To establish a sensitive and specific liquid
      chromatography-electrospray ionization (ESI)-tandem mass spectrometry (MS(n))
      methodology for the identification of the major constituents in Egyptian carob
      extract. MATERIALS AND METHODS: HPLC with diode array detector and ESI-mass
      spectrometry (MS) was developed for the identification and quantification of
      phenolic acids, flavonoid glycosides, and aglycones in the methanolic extract of
      Egyptian C. siliqua. The MS and MS(n) data together with HPLC retention time of
      phenolic components allowed structural characterization of these compounds. Peak
      integration of ions in the MS scans had been used in the quantification
      technique. RESULTS: A total of 36 compounds were tentatively identified. Twenty
      six compounds were identified in the negative mode corresponding to 85.4% of
      plant dry weight, while ten compounds were identified in the positive mode
      representing 16.1% of plant dry weight, with the prevalence of flavonoids (75.4%
      of plant dry weight) predominantly represented by two methylapigenin-O-pentoside
      isomers (20.9 and 13.7% of plant dry weight). CONCLUSION: The identification of
      various compounds present in carob pods opens a new door to an increased
      understanding of the different health benefits brought about by the consumption
      of carob and its products. SUMMARY: This research proposed a good example for the
      rapid identification of major constituents in complex systems such as herbs using
      sensitive, accurate and specific method coupling HPLC with DAD and MS, which
      facilitate the clarification of phytochemical composition of herbal medicine for
      better understanding of their nature and biological activities. Abbreviation
      used: HPLC: High performance liquid chromatography, DAD: Diode array detector,
      MS: Mass spectrometry, T R: Retention time.

PMID- 27041852
TI  - Steroidal Saponin Diosgenin from Dioscorea bulbifera Protects Cardiac Cells from
      Hypoxia-reoxygenation Injury Through Modulation of Pro-survival and Pro-death
      Molecules.
AB  - BACKGROUND: Diosgenin, a steroidal saponin from plants, exhibits many biological
      potentials. Herein, the cardioprotective role of diosgenin is studied. MATERIALS
      AND METHODS: The effect of diosgenin, isolated from Dioscorea bulbifera, was
      studied on hypoxia-reoxygenation (HR) in H9c2 cardiomyoblast cells. The amount of
      diosgenin in the plant extract was analyzed by high-performance thin layer
      chromatography using a solvent system comprising of chloroform:methanol:acetic
      acid:formic acid (13:4.5:1.5:1). Cardioprotection was checked by (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Further, the release
      of lactate dehydrogenase, an enzyme released during cell death was checked. The
      proteins responsible for cell death (Bax) and cell survival (Bcl-2, hemeoxygenase
      1 and Akt) were analyzed using Western blot to check the cardioprotective role of
      diosgenin. CONCLUSION: Supplementation of diosgenin mitigates HR injury, thereby
      exhibiting cardioprotective potential. SUMMARY: The cardioprotective effect of
      Diosgenin was evidenced from the improved cell survival after hypoxia
      reoxygenation injury demonstrated through MTT cell survival assay.The release of
      lactate dehydrogenase, an enzyme released during cell death was decreased by
      Diosgenin.Diosgenin upregulated the pro-survival molecules like B-cell lymphoma 2
      (Bcl-2), heme oxygenase-1 and the phosphorylation of ATK (at serine 473); and at
      the same time pro-.death molecules like Bax was downregulated.Thus, Diosgenin as
      a plant based steroidal saponin is confirmed to mitigate ischemic reperfusion
      injury. Figure.

PMID- 27041853
TI  - Molecular Docking Analysis of Selected Clinacanthus nutans Constituents as
      Xanthine Oxidase, Nitric Oxide Synthase, Human Neutrophil Elastase, Matrix
      Metalloproteinase 2, Matrix Metalloproteinase 9 and Squalene Synthase Inhibitors.
AB  - BACKGROUND: Clinacanthus nutans (Burm. f.) Lindau has gained popularity among
      Malaysians as a traditional plant for anti-inflammatory activity. OBJECTIVE: This
      prompted us to carry out the present study on a selected 11 constituents of C.
      nutans which are clinacoside A-C, cycloclinacoside A1, shaftoside, vitexin,
      orientin, isovitexin, isoorientin, lupeol and beta-sitosterol. MATERIALS AND
      METHODS: Selected 11 constituents of C. nutans were evaluated on the docking
      behavior of xanthine oxidase (XO), nitric oxide synthase (NOS), human neutrophil
      elastase (HNE), matrix metalloproteinase (MMP 2 and 9), and squalene synthase
      (SQS) using Discovery Studio Version 3.1. Also, molecular physicochemical,
      bioactivity, absorption, distribution, metabolism, excretion, and toxicity
      (ADMET), and toxicity prediction by computer assisted technology analyzes were
      also carried out. RESULTS: The molecular physicochemical analysis revealed that
      four ligands, namely clinacoside A-C and cycloclinacoside A1 showed nil
      violations and complied with Lipinski's rule of five. As for the analysis of
      bioactivity, all the 11 selected constituents of C. nutans exhibited active score
      (>0) toward enzyme inhibitors descriptor. ADMET analysis showed that the ligands
      except orientin and isoorientin were predicted to have Cytochrome P4502D6
      inhibition effect. Docking studies and binding free energy calculations revealed
      that clinacoside B exhibited the least binding energy for the target enzymes
      except for XO and SQS. Isovitexin and isoorientin showed the potentials in the
      docking and binding with all of the six targeted enzymes, whereas vitexin and
      orientin docked and bound with only NOS and HNE. CONCLUSION: This present study
      has paved a new insight in understanding these 11 C. nutans ligands as potential
      inhibitors against XO, NOS, HNE, MMP 2, MMP 9, and SQS. SUMMARY: Isovitexin and
      isoorientin (Clinacanthus nutans constituent) showed potentials in the docking
      and binding with all of the six targeted enzymes (xanthine oxidase [XO], nitric
      oxide synthase [NOS], human neutrophil elastase [HNE], matrix metalloproteinase
      [MMP 2 and 9], and squalene synthase [SQS])Moreover, clinacoside B (C. nutans
      constituent) exhibited the least binding energy for the target enzymes except for
      XO and SQSInterestingly, all of the selected ligands from C. nutans showed the
      potential to dock and bind with HNE. Abbreviations used: C. nutans: Clinacanthus
      nutans, XO: Xanthine oxidase, NOS: Nitric oxide synthase, HNE: Human neutrophil
      elastase, MMP: Matrix metalloproteinase, SQS: Squalene synthase, ADMET:
      Absorption, Distribution, Metabolism, Excretion, and Toxicity, TOPKAT: Toxicity
      prediction by the computer assisted technology.

PMID- 27041854
TI  - Potential Antidepressant Constituents of Nigella sativa Seeds.
AB  - BACKGROUND: Nigella sativa Linn. is well known seed in the Middle East, Asia, and
      the Far East as a natural remedy for many ailments and as a flavoring agent
      proclaimed medicinal usage dating back to the ancient Egyptians, Greeks, and
      Romans. An authentic saying of the Prophet Muhammad (Peace Be Upon Him) about
      black seed is also quoted in Al-Bukhari. OBJECTIVE: This study was carried out to
      evaluate the antidepressant effect and isolate the potential antidepressant
      constituents of the polar extract of N. sativa seeds. MATERIALS AND METHODS: The
      antidepressant effect was evaluated through the immobility duration in tail
      suspension and forced swim tests (FSTs). Albino mice were orally treated with N.
      sativa polar extract and its RP-18 column chromatography fractions (50 and 100
      mg/kg,). RESULTS: The polar extract and two of its sub-fractions were
      significantly able to decrease the immobility time of mice when subjected to both
      tail suspension and FSTs, the effects are comparable to standard drug
      (Sertraline, 5 mg/kg). However, these treatments did not affect the number of
      crossings and rearing in the open field test. Phytochemical investigation of the
      two active fractions led to the isolation of quercetin-3-O-alpha-L
      rhamnopyranoside 1, quercetin-7-O-beta-D-gluco- pyranoside 2, tauroside E 3, and
      sapindoside B as the potential antidepressant constituents. SUMMARY:
      Phytochemical and biological evaluation the antidepressant constituents in
      Nigella sativa using the tail suspension and forced swim methods afforded the
      isolation and identification of quercetin-3-O-alpha-L rhamnopyranoside, quercetin
      7-O-beta-D gluco pyranoside, tauroside E, and sapindoside B as the potential
      antidepressant constituents in the polar extract of N. sativa. The isolated
      compounds were identified through extensive NMR analysis (1D, 2D, ESI MS).
      Abbreviations used: TST: Tail suspension test, FST: Forced swim test, OFT: An
      Open field test.

PMID- 27041855
TI  - Reverse Phase-ultra Flow Liquid Chromatography-diode Array Detector
      Quantification of Anticancerous and Antidiabetic Drug Mangiferin from 11 Species
      of Swertia from India.
AB  - BACKGROUND: Genus Swertia is valued for its great medicinal potential, mainly
      Swertia chirayita (Roxb. ex Fleming) H. Karst. is used in traditional medicine
      for a wide range of diseases. Mangiferin one of xanthoids is referred with
      enormous pharmacological potentials. OBJECTIVE: The aim of the study was to
      quantify and compare the anticancerous and antidiabetic drug mangiferin from 11
      Swertia species from India. The study also evaluates hierarchical relationships
      between the species based on mangiferin content using multivariate analysis.
      MATERIALS AND METHODS: The reverse phase-ultra flow liquid chromatography-diode
      array detector analyses was performed and chromatographic separation was achieved
      on a Lichrospher 100, C18e (5 MUm) column (250-4.6 mm). Mobile phase consisting
      of 0.2% triethylamine (pH-4 with O-phosphoric acid) and acetonitrile (85:15) was
      used for separation with injection volume 20 MUL and detection wave length at 257
      nm. RESULTS: Results indicated that concentration of mangiferin has been found to
      vary largely between Swertia species collected from different regions. Content of
      mangiferin was found to be highest in Swertia minor compared to other Swertia
      species studied herein from the Western Ghats and Himalayan region also. The same
      was also evident in the multivariate analysis, wherein S. chirayita, S. minor and
      Swertia paniculata made a separate clade. CONCLUSION: Conclusively, the work
      herein provides insights of mangiferin content from 11 Swertia species of India
      and also presents their hierarchical relationships. To best of the knowledge this
      is the first report of higher content of mangiferin from any Swertia species.
      SUMMARY: The present study quantifies and compares mangiferin in 11 species of
      Swertia from India. The study also evaluates hierarchical relationships between
      the species based on mangiferin content using multivariate analysis. The
      mangiferin content was highest in S. minor compared to the studied Swertia
      species. To the best of our knowledge this is the first report of higher content
      of mangiferin from Swertia species. Abbreviations used: LOD: Limit of detection,
      LOQ: Limit of quantification, RP-UFLC-DAD: Reverse phase-ultra flow liquid
      chromatography-diode array detector, RSD: Relative standard deviation, SAN:
      Swertia angustifolia, SAP: Swertia angustifolia var. pulchella, SBI: S.
      bimaculata, SCH: S. chirayita, SCO: S. corymbosa, SDE: S. densifolia, SDI: S.
      dialatata, SLA: S. lawii, SMI: S. minor; SNE: S. nervosa, and SPA: S. paniculata.

PMID- 27041856
TI  - Crispene A, B, C and D, Four New Clerodane Type Furanoid Diterpenes from
      Tinospora crispa (L.).
AB  - BACKGROUND: Tinospora crispa (L.) is used to alleviate the symptoms of diabetes
      mellitus in folk medicine. It is also used for hypertension and to treat malaria,
      remedy for diarrhea, and as vermifuge. MATERIALS AND METHODS: Stems of T. crispa
      were collected, sun dried for several days followed by oven dried for 24 h at a
      considerably low temperature and then ground into coarse powder. The powdered
      stems were soaked in methanol at room temperature for 14 days with occasional
      shaking. The extract was collected by filtration, and the solvent was evaporated
      under reduced pressure in a rotary evaporator to obtain a solid residue which was
      then subjected to fractionation using the modified Kupchan partitioning method
      into n-hexane, CCl4, CHCl3 and aqueous soluble fractions. The n-hexane soluble
      fraction was chromatographed over sephadex (LH-20) and the column was eluted with
      n-hexane: CH2Cl2:MeOH (2:5:1) followed by CH2Cl2:MeOH (9:1) and MeOH (100%) in
      order to increase the polarities. The column fractions were then concentrated and
      subjected to thin layer chromatography screening and the fractions with a
      satisfactory resolution of compounds were rechromatographed over silica gel to
      isolate the pure compounds. RESULTS: Four new furanoid diterpenes of clerodane
      types, Crispene A, B, C, and D (1-4), including one known furanoid diterpene
      glucoside, borapetoside E (5), were isolated from the stems of T. crispa. The
      structures of these compounds were elucidated by means of extensive spectroscopic
      analysis and by comparison of their spectral data with closely related compounds.
      CONCLUSION: We have reported four new furanoid diterpenes of clerodane types,
      including one known furanoid diterpene glucoside. This is the first report of any
      clerodane diterpene having olefinic bond between C-6 and C-7. SUMMARY: Crispene
      A, B, C, and D, four new furanoid diterpenes of clerodane types from Tinospora
      crispaCrispene C, an unusual furanoid diterpene with olifinic bond between C-6
      and C-7First report of Crispene D as a free aglycone, though it was earlier
      reported as an enzymatic hydrolysis product. Abbreviation used: TLC: Thin layer
      chromatography, NMR: Nuclear magnetic resonance, COSY: Correlation spectroscopy,
      NOE: Nuclear overhauser effect, HPLC: High-performance liquid chromatography, ESI
      MS: Electrospray ionization mass spectroscopy.

PMID- 27041857
TI  - Essential Oil from the Resin of Protium heptaphyllum: Chemical Composition,
      Cytotoxicity, Antimicrobial Activity, and Antimutagenicity.
AB  - BACKGROUND: Protium heptaphyllum (Aubl.) March is popularly used as an analgesic
      and anti-inflammatory agent. OBJECTIVE: This study aimed to evaluate the chemical
      composition of P. heptaphyllum essential oil, its cytotoxicity in a breast cancer
      cell line (MCF-7), antimicrobial activity, and its antimutagenicity in vivo.
      MATERIALS AND METHODS: The chemical composition of the essential oil collected in
      three 3 years was determined by gas chromatography-mass spectrometry. The
      cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Annexin V conjugated with fluorescein
      isothiocyanate, caspase-3, and tumor necrosis factor-alpha (TNF-alpha) assays
      were performed to evaluate apoptosis and inflammatory events. The antimutagenic
      activity at doses of 25, 50, and 100 mg/kg was determined using a micronucleus
      test in murine bone marrow. RESULTS: The essential oil showed a predominance of
      monoterpene compounds, being the terpinolene, p-cymene-8-ol, and p-cymene,
      present in the essential oil extracted in the 3 years. The essential oil showed a
      protection against cyclophosphamide-induced genotoxicity, and the cytotoxicity
      index polychromatic erythrocytes/normochromatic erythrocytes ratio in animals
      treated with oil at all doses (1.34 +/- 0.33; 1.15 +/- 0.1; 1.11 +/- 0.13) did
      not differ from the negative control animal (1.31 +/- 0.33), but from the
      cyclophosphamide group (0.61 +/- 0.12). Cytotoxicity, at a concentration of 40.0
      MUg/mL, and antimicrobial activity were not observed for the essential oil
      (minimum inhibitory concentration >=0.5 mg/mL). The essential oil did not change
      the levels of caspase-3 in the TNF-alpha level. CONCLUSION: The essential oil
      showed antimutagenic activity due to its chemical composition. SUMMARY:
      Terpinolene, p-cymene-8-ol, and p-cymene are the main constituents of the
      essential oil of P. heptaphyllum collected within 3-yearsThe essential oil of P.
      heptaphyllum did not show antimicrobial activity (MIC >0.5 mg/mL) against E.
      coli, S. aureus, E. faecalis, and C. albicansThe essential oil of P. heptaphyllum
      has activity against S. mutans (MIC = 0.5 mg/mL)The essential oil showed a
      protection against cyclophosphamide-induced genotoxicity in the micronuclei
      assay. Abbreviations used: GC-MS: Gas Chromatography-Mass Spectrometry, MTT: 3
      (4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Annexin V-FITC:
      Annexin V conjugated with fluorescein isothiocyanate, TNF-alpha: Tumor necrosis
      factor alpha, MIC: Minimum Inhibitory Concentration.

PMID- 27041858
TI  - New Isorhamnetin Derivatives from Salsola imbricata Forssk. Leaves with Distinct
      Anti-inflammatory Activity.
AB  - BACKGROUND: Salsola imbricata Forssk. is a shrub widely growing in Egypt, used as
      a camel food, traditionally, used as anti-inflammatory agent. Literature survey
      showed no report about the anti-inflammatory activity of S. imbricata. AIM OF THE
      STUDY: This work was designed to study the phenolic constituents and to provide
      evidence for the traditional use of S. imbricata as an anti-inflammatory agent.
      MATERIALS AND METHODS: The in vitro anti-inflammatory activity of the total
      aqueous methanol extract and some isolated compounds were investigated in RAW
      264.7 macrophage cells using nitric oxide assay. All chemical structures were
      identified on the basis of electrospray ionization-mass spectrometry, one- and
      two-dimension nuclear magnetic resonance. RESULTS: Nine phenolic compounds, among
      them two new natural products; isorhamnetin-3-O-beta-D-glucuronyl (1'''->4'')
      glucuronide (1) and its dimethyl ester; isorhamnetin-3-O-beta-D-di glucuronate
      dimethyl ester (2), two isorhamnetin glycosides: Isorhamnetin-3-O-beta-D
      galactopyranoside (3), isorhamnetin-3-O-beta-D-glucopyranoside (4), and
      isorhamnetin (5). In addition, an alkaloidal phenolic; trans N-feruloyl tyramine
      (6), three phenolic acids: Isovanillic acid (7), ferulic acid (8), and p-hydroxy
      benzoic acid (9) were isolated from salsola imbricata leaves. All compounds were
      isolated and identified for the first time from this plant except compound (6).
      The extract and the tested compounds showed distintict anti-inflammatory
      activities with no toxicity on RAW 264.7 macrophage cells. CONCLUSION: The
      extract and the tested compounds showed distintict anti-inflammatory activities
      with no toxicity on RAW 264.7 macrophage cells. SUMMARY: Investigation of the
      chemical constituents of the leaves of Salsola imbricata led to isolation of two
      new isorhamnetin derivatives: isorhamnetin.3-O-beta-D.glucuronyl (1'"->")
      glucuronide (1) and its dimethyl ester (2), together with seven known phenolic
      compounds. The extract and the tested compounds showed distintict anti
      inflammatory activities with no toxicity on RAW 264.7 macrophage cells.
      Abbreviations used: PC: Paper chromatography, MPLC : Medium Pressure Liquid
      Chromatography, HMBC: Heteronuclear multiple bond correlation, HMQC:
      Heteronuclear single quantum correlation, NMR: Nuclear magnetic resonance.

PMID- 27041859
TI  - Cytotoxic Properties and Complete Nuclear Magnetic Resonance Assignment of
      Isolated Xanthones from the Root of Garcinia cowa Roxb.
AB  - OBJECTIVE: To isolate compounds from the roots of Garcinia cowa and to evaluated
      their cytotoxic activity against breast (MCF-7), prostate (DU-145), and lung (H
      460) cell lines. MATERIALS AND METHODS: The ground air-dried root was
      sequentially macerated with hexane, dichloromethane (DCM), ethyl acetate (EtOAc),
      and methanol. The DCM soluble extract was fractionated by vacuum liquid
      chromatography, column chromatography, and radial chromatography over silica gel
      with hexane, EtOAc and methanol as eluent in progressively increasing polarity
      manner; to yield three compounds. Their structures were elucidated based on their
      spectroscopic data and their comparison with those of the literature. The
      cytotoxicity of isolated compounds was carried out against human cell lines by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay.
      The extract was added at various concentrations (0.1, 1, 10 and 100 mg/ml). The
      level of cytotoxicity was determined by calculating the level of IC50 that was
      based on the percentage of the cell death following the 24 h incubation with the
      extract. RESULTS: Phytochemical study on the roots of G. cowa yielded
      rubraxanthone (3), cowanine (4) and 1,5-dihydroxyxanthone (5). Compound 4 with an
      IC50 value of 4.1 +/- 1.0 MUM, 5.4 +/- 2.3 MUM and 11.3 +/- 10.0 MUM against MCF
      7, H-460, and DU-145, respectively while compound 3 was found to be in active.
      CONCLUSION: The results indicate that G. cowa roots could be important sources of
      natural cytotoxic compounds. SUMMARY: Isolation of cytotoxic compounds from
      Garcinia cowaCowanine is the active constituent from the roots of Garcinia
      cowaComplete nuclear magnetic resonance assignment of isolated compoundsMS
      fragmentation of rubraxanthone.

PMID- 27041860
TI  - New Synthetic Pyrazine Carboxamide Derivatives as Potential Elicitors in
      Production of Secondary Metabolite in In vitro Cultures.
AB  - BACKGROUND: Silymarin, an active polyphenolic fraction of Silybum marianum, and
      high flavonoid content of Fagopyrum possess various interesting biological
      activities. The substituted pyrazine-2-carboxamides were previously used as
      effective elicitors of studied secondary metabolites. OBJECTIVE: To study the
      effect of new synthetic pyrazine carboxamide derivatives, N-(4-chlorobenzyl)-5
      tert-butylpyrazine-2-carboxamide (1) and 3-(3-((trifluoromethyl) benzyl) amino)
      pyrazine-2-carboxamide (2), on flavonolignan and flavonoid production in S.
      marianum and Fagopyrumes culentum in vitro cultures. MATERIALS AND METHODS:
      Callus and suspension cultures were cultured on MS medium containing alpha
      naphtaleneacetic acid or 2,4-D. Three elicitor concentrations for different
      exposure times were tested. Dried and powdered samples of callus and suspension
      cultures were extracted with methanol and analyzed by DAD-HPLC. RESULTS: Compound
      1 showed as a good elicitor of taxifolin production. The effect on silymarin
      complex was less visible with a maximum between 24 and 48 h after 3.292 *10(-4)
      mol/L concentration. The detailed analysis showed that silychristin was the most
      abundant. Compound 2 was effective in rutin production only in callus culture
      with maximum 24 h and 168 h after application of 3.3756 *10(-3) mol/L
      concentration and 48 and 72 h after 3.3756 *10(-4) mol/L concentration.
      CONCLUSION: From the results of the performed experiments, it can be concluded
      that compound 1 shows to be suitable elicitor for enhanced production of
      taxifolin and silychristin in S. marianum, mainly when 3.292 *10(-4) mol/L
      concentration was used, and compound 2 is suitable for increase rutin production
      in callus cultures and less appropriate for suspension cultures of F. esculentum.
      SUMMARY: The influence of two new synthetic pyrazine-2-carboxamidesderivatives on
      secondary metabolite content of Silybum marianum and Fagopyrum esculentum in
      vitro cultures was tested.In S. marianum, the derivate N-(4-chlorobenzyl)-5-tert
      butylpyrazine-2-carboxamide showed as a good elicitor of taxifolin production and
      less effective for silymarin complex production with silychristin as the most
      abundant.The derivate 3-(3-((trifluoromethyl) benzyl) amino) pyrazine-2
      carboxamide is suitable for increase rutin production in callus cultures and less
      appropriate for suspension cultures of F. esculentum.

PMID- 27041861
TI  - Naringin and Rutin Alleviates Episodic Memory Deficits in Two Differentially
      Challenged Object Recognition Tasks.
AB  - BACKGROUND: Cognitive decline or dementia is a debilitating problem of
      neurological disorders such as Alzheimer's and Parkinson's disease, including
      special conditions like chemobrain. Dietary flavonoids proved to be efficacious
      in delaying the incidence of neurodegenerative diseases. Two such flavonoids,
      naringin (NAR) and rutin (RUT) were reported to have neuroprotective potential
      with beneficial effects on spatial and emotional memories in particular. However,
      the efficacy of these flavonoids is poorly understood on episodic memory, which
      comprises an important form of autobiographical memory. OBJECTIVE: This study
      objective is to evaluate NAR and RUT to reverse time-delay-induced long-term and
      scopolamine-induced short-term episodic memory deficits in Wistar rats. MATERIALS
      AND METHODS: We have evaluated both short-term and long-term episodic memory
      forms using novel object recognition task. Open field paradigm was used to assess
      locomotor activity for any confounding influence on memory assessment. Donepezil
      was used as positive control and was effective in both models at 1 mg/kg, i.p.
      RESULTS: Animals treated with NAR and RUT at 50 and 100 mg/kg, p.o. spent
      significantly more time exploring novel object compared to familiar one, whereas
      control animals spent almost equal time with both objects in choice trial. NAR
      and RUT dose-dependently increased recognition and discriminative indices in time
      induced long-term as well as scopolamine-induced short-term episodic memory
      deficit models without interfering with the locomotor activity. CONCLUSION: We
      conclude that, NAR and RUT averted both short- and long-term episodic memory
      deficits in Wistar rats, which may be potential interventions for
      neurodegenerative diseases as well as chemobrain condition. SUMMARY: Incidence of
      Alzheimer's disease is increasing globally and the current therapy is only
      symptomatic. Curative treatment is a major lacuna. NAR and RUT are natural
      flavonoids proven for their pleiotropic pharmacological effects with potential
      neuroprotective benefits. The study evaluated these flavonoids for their
      potential to improve the most common form of episodic memory (memory of
      autobiographical events in relation to time, places etc.) in two differential
      animal models assessing short-term and long-term memory, respectively. We also
      found that NAR and RUT were able to reverse both short-term and long-term memory
      deficits dose dependently in female Wistar rats. Abbreviations used: AD:
      Alzheimer's disease, AChE: Acetylcholinesterase, COX: Cyclooxygenase, DI:
      Discriminative index, ITI: Inter trial interval, NAR: Naringin, RUT: Rutin, NORT:
      Novel object recognition task, NOS: Nitric oxide synthase, QOL: Quality of life,
      RI: Recognition index, WFI: Water for injection.

PMID- 27041862
TI  - Alteration in Memory and Electroencephalogram Waves with Sub-acute Noise Stress
      in Albino Rats and Safeguarded by Scoparia dulcis.
AB  - BACKGROUND: Noise stress has different effects on memory and novelty and the link
      between them with an electroencephalogram (EEG) has not yet been reported.
      OBJECTIVE: To find the effect of sub-acute noise stress on the memory and novelty
      along with EEG and neurotransmitter changes. MATERIALS AND METHODS: Eight-arm
      maze (EAM) and Y-maze to analyze the memory and novelty by novel object test.
      Four groups of rats were used: Control, control treated with Scoparia dulcis
      extract, noise exposed, and noise exposed which received Scoparia extract.
      RESULTS: The results showed no marked difference observed between control and
      control treated with Scoparia extract on EAM, Y-maze, novel object test, and EEG
      in both prefrontal and occipital region, however, noise stress exposed rats
      showed significant increase in the reference memory and working memory error in
      EAM and latency delay, triad errors in Y-maze, and prefrontal and occipital EEG
      frequency rate with the corresponding increase in plasma corticosterone and
      epinephrine, and significant reduction in the novelty test, and significant
      reduction in the novelty test, amplitude of prefrontal, occipital EEG, and
      acetylcholine. CONCLUSION: These noise stress induced changes in EAM, Y-maze,
      novel object test, and neurotransmitters were significantly prevented when
      treated with Scoparia extract and these changes may be due to the normalizing
      action of Scoparia extract on the brain, which altered due to noise stress.
      SUMMARY: Noise stress exposure causes EEG, behavior, and neurotransmitter
      alteration in the frontoparietal and occipital regions mainly involved in
      planning and recognition memoryOnly the noise stress exposed animals showed the
      significant alteration in the EEG, behavior, and neurotransmittersHowever, these
      noise stress induced changes in EEG behavior and neurotransmitters were
      significantly prevented when treated with Scoparia extractThese changes may be
      due to the normalizing action of Scoparia dulcis (adoptogen) on the brain which
      altered by noise stress. Abbreviations used: EEG: Electroencephalogram, dB:
      Decibel, EPI: Epinephrine, ACH: Acetylcholine, EAM: Eight-arm maze.

PMID- 27041863
TI  - Hybrid analysis (barcode-high resolution melting) for authentication of Thai
      herbal products, Andrographis paniculata (Burm.f.) Wall.ex Nees.
AB  - BACKGROUND: Andrographis paniculata Nees is a medicinal plant with multiple
      pharmacological properties. It has been used over many centuries as a household
      remedy. A. paniculata products sold on the markets are in processed forms so it
      is difficult to authenticate. Therefore buying the herbal products poses a high
      risk of acquiring counterfeited, substituted and/or adulterated products. Due to
      these issues, a reliable method to authenticate products is needed. MATERIALS AND
      METHODS: High resolution melting analysis coupled with DNA barcoding (Bar-HRM)
      was applied to detect adulteration in commercial herbal products. The rbcL
      barcode was selected to use in primers design for HRM analysis to produce
      standard melting profile of A. paniculata species. DNA of the tested commercial
      products was isolated and their melting profiles were then generated and compared
      with the standard A. paniculata. RESULTS: The melting profiles of the rbcL
      amplicons of the three closely related herbal species (A. paniculata, Acanthus
      ebracteatus and Rhinacanthus nasutus) are clearly separated so that they can be
      distinguished by the developed method. The method was then used to authenticate
      commercial herbal products. HRM curves of all 10 samples tested are similar to A.
      paniculata which indicated that all tested products were contained the correct
      species as labeled. CONCLUSION: The method described in this study has been
      proved to be useful in aiding identification and/or authenticating A. paniculata.
      This Bar-HRM analysis has allowed us easily to determine the A. paniculata
      species in herbal products on the markets even they are in processed forms.
      SUMMARY: We propose the use of DNA barcoding combined with High Resolution
      Melting analysis for authenticating of Andrographis paniculata products.The
      developed method can be used regardless of the type of the DNA template (fresh or
      dried tissue, leaf, and stem).rbcL region was chosen for the analysis and work
      well with our samplesWe can easily determine the A. paniculata species in herbal
      products tested. Abbreviations used: bp: Base pair, Tm: Melting temperature.

PMID- 27041864
TI  - Protective Mechanisms of Thymoquinone on Methotrexate-induced Intestinal Toxicity
      in Rats.
AB  - BACKGROUND: Intestinal toxicity is a serious side effect in methotrexate (MTX)
      chemotherapy. OBJECTIVE: To investigate the mechanisms by which the anticancer
      drug MTX-induced intestinal damage could be prevented by thymoquinone (TQ), an
      active ingredient of Nigella sativa. MATERIALS AND METHODS: TQ was given orally
      for 10 days, and MTX toxicity was induced at the end of day 3 of the experiment,
      with or without TQ pretreatment. RESULTS: MTX caused intestinal damage,
      represented by distortion in normal intestinal histological structure, with
      significant oxidative stress, exhibited as decrease in reduced glutathione
      concentration and catalase activity, along with significant increase in
      malondialdehyde level compared to control group. MTX also caused nitrosative
      stress evident by increased intestinal nitric oxide (NO) level, with up
      regulation of inducible NO synthase expression shown in immunohistochemical
      staining. Furthermore, MTX caused inflammatory effects as evident by up
      regulation of intestinal necrosis factor-kappa beta and cyclooxygenase-2
      expressions, which were confirmed by increased intestinal tumor necrosis factor
      alpha level via enzyme-linked immunosorbent assay. Moreover, MTX caused apoptotic
      effect, as it up-regulated intestinal caspase 3 expression. Concomitant TQ
      significantly reversed the MTX-induced intestinal toxic effects by reversing
      intestinal microscopic damage, as well as significantly improving
      oxidative/nitrosative stress, inflammatory and apoptotic markers tested compared
      to MTX alone. CONCLUSION: TQ may possess beneficial intestinal protective effects
      as an adjuvant co-drug against MTX intestinal toxicity during cancer
      chemotherapy. TQ protection is conferred via antioxidant, anti-nitrosative, anti
      inflammatory, and anti-apoptotic mechanisms. SUMMARY: Methotrexate induces
      oxidative and nitrosative stress in intestinal tissuesMethotrexate also initiates
      inflammatory and apoptotic intestinal injuryThymoquinone co-administration
      ameliorates methotrexate-induced intestinal toxicityThymoquinone has
      antioxidative, anti-nitrosative, anti-inflammatory, and anti-apoptotic
      mechanisms. Abbreviations used: COX-2: Cyclooxygenase-2, ELISA: Enzyme-linked
      immunosorbent assay, H and E: Hematoxylin and eosin, iNOS: Inducible nitric oxide
      synthase, MDA: Malondialdehyde, MTX: Methotrexate, NO: Nitric oxide, NF-kappaB:
      Nuclear factor-kappaB, GSH: Reduced glutathione, TQ: Thymoquinone, TNF-alpha:
      Tumor necrosis factor-alpha.

PMID- 27041865
TI  - Bioactivities of Ethanolic Extract and its Fractions of Cistus laurifolius L.
      (Cistaceae) and Salvia wiedemannii Boiss. (Lamiaceae) Species.
AB  - BACKGROUND: Cistus laurifolius L. (Cistaceae) and Salvia wiedemannii Boiss.
      (Lamiaceae) have been used for treatment of some illnesses in Turkish folk
      medicine. In the present study, the ethanolic extract and its fractions obtained
      using re-extraction by hexane (Hx), chloroform (CHCl3), butanol, and remaining
      water (r-H2O) of C. laurifolius were screened for their in vitro bioactivities.
      MATERIALS AND METHODS: Activities were determined against both standard and the
      isolated strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis,
      Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus,
      Enterococcus faecalis, as well as yeasts such as Candida albicans and Candida
      parapsilosis by microdilution method. Also, antiviral activity of C. laurifolius
      and S. wiedemannii extracts were tested on herpes simplex virus-1 (HSV-1) and
      parainfluenza-3 (PI-3) using Madin-Darby bovine kidney and vero cell lines.
      RESULTS: Tested extracts of C. laurifolius (minimum inhibitory concentration 32
      MUg/mL) exerted a strong antimicrobial activity against Gram-negative bacteria of
      E. coli, P. mirabilis, K. pneumoniae, and A. baumannii. CONCLUSION: The Hx
      extract of C. laurifolius (cytopathogenic effect of 32-8 MUg/mL) had antiviral
      activity on PI-3. Also, the r-H2O, CHCl3, and ethanol extracts (16-<0.25 MUg/mL)
      of S. wiedemannii had significant antiviral activity on HSV-1, same as control.
      SUMMARY: The objective of this study was to evaluate the bioactivity of plant
      extracts used in folk medicineEthanolic extract and its fractions obtained using
      re-extraction by hexane (Hx), chloroform (CHCl3), butanol, and remaining-water (r
      H2O) of Cistus laurifolius L. (Cistaceae) and Salvia wiedemannii Boiss.
      (Lamiaceae) were screened against both standard and the isolated strains of E.
      coli, P. aeruginosa, P. mirabilis, K. pneumoniae, A. baumannii, S. aureus, E.
      faecalis, C. albicans and C. parapsilosis by microdilution methodAntiviral
      activity were tested on HSV-1 and PI-3 using MDBK and Vero cell linesExtracts of
      C. laurifolius exerted a strong antimicrobial activity against E. coli, P.
      mirabilis, K. pneumoniae, and A. baumannii(MIC; 32 MUg/mL)The Hx extract of C.
      laurifolius had antiviral activity on PI-3 (CPE; 32-8 MUg/mL). Also, the r-H2O,
      CHCl3, and ethanol extracts (16-<0.25 MUg/mL) of S. wiedemannii had significant
      antiviral activity.

PMID- 27041866
TI  - Endoplasmic reticulum stress-induced apoptotic pathway and mitochondrial
      dysregulation in HeLa cells treated with dichloromethane extract of Dillenia
      suffruticosa.
AB  - Ethyl acetate and dichloromethane extract of Dillenia suffruticosa (EADS and
      DCMDS, respectively) can be a potential anticancer agent. The effects of EADS and
      DCMDS on the growth of HeLa cervical cancer cells and the expression of apoptotic
      related proteins had been investigated in vitro. Cytotoxicity of the extracts
      toward the cells was determined by 5-diphenyltetrazolium bromide assay, the
      effects on cell cycle progression and the mode of cell death were analyzed by
      flow cytometry technique, while the effects on apoptotic-related genes and
      proteins were evaluated by quantitative real-time polymerase chain reaction, and
      Western blot and enzyme-linked immunosorbent assay, respectively. Treatment with
      DCMDS inhibited (P < 0.05) proliferation and induced apoptosis in HeLa cells. The
      expression of cyclin B1 was downregulated that led to G2/M arrest in the cells
      after treatment with DCMDA. In summary, DCMDS induced apoptosis in HeLa cells via
      endoplasmic reticulum stress-induced apoptotic pathway and dysregulation of
      mitochondria. The data suggest the potential application of DCMDS in the
      treatment of cervical cancer. 

PMID- 27041867
TI  - Biological activities of Croton palanostigma Klotzsch.
AB  - BACKGROUND: Different species of Croton are used in traditional Amazonian
      medicine. Among the popular uses are treatment of bacterial diseases, poorly
      healing wounds and fevers. OBJECTIVE: This study evaluated the antileishmanial,
      antiplasmodial and antimicrobial activities of the extracts and diterpenes of
      Croton palanostigma Klotzsch (Euphorbiaceae). MATERIALS AND METHODS: Leaves and
      bark were extracted with dichloromethane and methanol. The bark dichloromethane
      extract (BDE) was chromatographed on a column, obtaining cordatin and
      aparisthman. The extracts and diterpenes were assayed thought agar disk diffusion
      method and their bactericidal or fungicidal effects were evaluated by minimum
      bactericidal or fungicidal concentration. The antiplasmodial activity was
      evaluated after 24 and 72 h of exposition. The antileishmanial activity was
      performed on promastigotes forms of Leishmania amazonensis. RESULTS: The bark
      methanol extract (BME) and cordatin were not active against any microbial strains
      tested; BDE and leaves methanol extract (LME) were positive for Pseudomonas
      aeruginosa and aparisthman was positive for Candida albicans. In the
      determination of the minimum bactericidal concentration, neither of them were
      active in the highest concentration tested. The extracts and diterpenes were
      inactive in Plasmodium falciparum, except the LME in 72 h. Any extract was shown
      to be active in promastigote forms of L. amazonensis. CONCLUSION: These results
      indicate that the BDE and LME did not inhibit the bacterial growth, then they
      probably had bacteriostatic effect. LME presented activity in P. falciparum.

PMID- 27041868
TI  - Review of Naturopathy of Medical Mushroom, Ophiocordyceps Sinensis, in Sexual
      Dysfunction.
AB  - Sexual dysfunctions including desire, arousal, orgasm, and pain disorders are
      increasing worldwide due to etiological factors and aging. Several types of
      treatment are claimed in modern medicine, but they have serious side effects and
      higher costs. In fact, alternative approaches, such as the intake of plants,
      fungi, and insects, or their extracts, have also been practiced to enhance
      sexuality and ameliorate illness with notable successes. However, the scientific
      evidence related to the mechanisms and efficacy of these alternative medicines is
      both scarce and all too often unconvincing. Ophiocordyceps sinensis is an
      Ascomycetes fungus parasitic to Lepidoptera larvae, and has long been used as
      medicine to treat many illnesses and promote longevity in Chinese society.
      Previous investigations have shown that O. sinensis has many pharmacological
      activities. This review has focused on illustrating that O. sinensis can enhance
      libido and sexual performance, and can restore impaired reproductive functions,
      such as impotency or infertility, in both sexes. 

PMID- 27041869
TI  - Himatanthus Willd. ex Schult. (Apocynaceae): Review.
AB  - The genus Himatanthus Wild. ex Schult. (Apocynaceae) includes about 13 species
      and five subspecies widely distributed in South America, especially Brazil. The
      phytochemical reports on this genus have revealed mainly triterpenes and
      iridoids. The plants are traditionally used as anthelmintic, antitumor, and
      antiinflammatory agents. The most used parts of the plant are its bark, leaves,
      and latex. This review emphasizes the phytochemical constituents and medicinal
      properties, which may help in future research. The research was conducted with
      data obtained from books about medicinal plants, theses, dissertations, and
      articles in refereed journals. 

PMID- 27041870
TI  - Flavonoids from the Genus Astragalus: Phytochemistry and Biological Activity.
AB  - Flavonoids, the most common plant polyphenols are widely distributed in every
      species and possess a broad range of pharmacological activities. The genus
      Astragalus is the largest in the Fabaceae family with more than 2,500 species
      spread. They are known to contain different metabolites such as flavonoids,
      saponins, and polysaccharides. Plants from the genus have been used in the
      traditional medicine of many countries for centuries. This paper is focused on
      the large group of flavonoid compounds. Details on structure as well as
      information about the pharmacological properties of flavonoids, isolated from
      Astragalus species have been discussed. This review is based on publications
      until the first half of 2014 and includes also the results from our phytochemical
      investigations of the genus. 

PMID- 27041871
TI  - Review of Scientific Evidence of Medicinal Convoy Plants in Traditional Persian
      Medicine.
AB  - One concept used in traditional Persian medicine (TPM) for multidrug therapy is
      that of the convoy drug (Mobadregh). According to TPM texts, convoy drugs are
      substances (or drugs), which facilitate the access of drugs or foods to the whole
      body or to specific organs. This study reviewed some convoy drugs presented in
      TPM, their biological effects, and their probable interactions with main drugs,
      considering the increased absorption through inhibition of P-glycoprotein (P-gp)
      efflux function, bioavailability-enhancing effects, and decreased metabolism of
      the main drug using electronic databases including PubMed, Scopus, ScienceDirect,
      and Google Scholar in November and December, 2013. Recent studies have proven the
      beneficial effects of Crocus sativus L. (saffron) and camphor on the heart and
      brain, the cerebral therapeutic effects of Asarum europaeum (hazelwort), the
      hepatoprotective effects of Cichorium intybus (chicory), and Apium graveolens
      (celery) seeds, and the diuretic effects of Cinnamomum zeylanicum (cinnamon), and
      Cucumis melo (melon) seeds. The effects of vinegar in targeting the liver and
      brain have also been demonstrated. An evaluation of the results demonstrated that
      the suggested convoy drugs, including Piper nigrum (black pepper), Piper longum
      (long pepper), red wine, Camellia sinensis (tea), hazelwort, Mentha longifolia
      (pennyroyal), Anethum graveolens (dill), Foeniculum vulgare (fennel), cinnamon,
      and Sassafras albidum (sassafras) can increase the bioavailability of
      coadministered drugs by inhibition of P-gp or cytochrome P450s (CYP450s) or both
      of them. This evidence could be a good basis for the use of these agents as
      convoys in TPM. 

PMID- 27041872
TI  - Chitosan: A Promising Marine Polysaccharide for Biomedical Research.
AB  - Biomaterials created 50 years ago are still receiving considerable attention for
      their potential to support development in the biomedical field. Diverse naturally
      obtained polysaccharides supply a broad range of resources applicable in the
      biomedical field. Lately, chitosan, a marine polysaccharide derived from chitins
      which are extracted from the shells of arthropods such as crab, shrimp, and
      lobster-is becoming the most wanted biopolymer for use toward therapeutic
      interventions. This is a general short review of chitosan, highlighting the
      history, properties, chemical structure, processing method, and factors
      influencing the usage of chitosan derivatives in the biomedical field. 

PMID- 27041873
TI  - Therapeutic Potential of Pterocarpus santalinus L.: An Update.
AB  - Recently there has been increasing interest in plants and plant-derived compounds
      as raw food and medicinal agents. In Ayurveda, an Indian system of traditional
      medicine, a wide spectrum of medicinal properties of Pterocarpus santalinus is
      described. Many important bioactive phytocompounds have been extracted and
      identified from the heartwood of P. santalinus. Bioactive compounds typically
      occur in small amounts and have more subtle effects than nutrients. These
      bioactive compounds influence cellular activities that modify the risk of disease
      rather than prevent deficiency diseases. A wide array of biological activities
      and potential health benefits of P. santalinus have been reported, including
      antioxidative, antidiabetic, antimicrobial, anticancer, and anti-inflammatory
      properties, and protective effects on the liver, gastric mucosa, and nervous
      system. All these protective effects were attributed to bioactive compounds
      present in P. santalinus. The major bioactive compounds present in the heartwood
      of P. santalinus are santalin A and B, savinin, calocedrin, pterolinus K and L,
      and pterostilbenes. The bioactive compounds have potentially important health
      benefits: These compounds can act as antioxidants, enzyme inhibitors and
      inducers, inhibitors of receptor activities, and inducers and inhibitors of gene
      expression, among other actions. The present review aims to understand the
      pharmacological effects of P. santalinus on health and disease with "up-to-date"
      discussion. 

PMID- 27041874
TI  - Review of the Phytochemical and Pharmacological Studies of the Genus Markhamia.
AB  - Natural product compounds obtained from medicinal plants have been great
      contributions in the discovery of numerous clinically useful drugs. Markhamia
      species have been reportedly used by many cultures in human and veterinary
      traditional medicines. The five identified species of Markhamia, that is,
      Markhamia lutea, Markhamia obtusifolia, Markhamia stipulata, Markhamia tomentosa,
      and Markhamia zanzibarica have been the subject of chemical investigations that
      have led to the characterization of their secondary metabolites. Plants of the
      genus with the identified phytoconstituents, including phenylpropanoid glycosides
      (PhGs), terpenoids, phytosterols, lignans, quinones, and flavonoids, have been
      claimed to possess antiviral, antifungal, antiprotozoal, analgesic,
      antiinflammatory, and cytotoxic activities. In vitro and in vivo pharmacological
      research studies have reported the validation of the medicinal properties of
      plants of this genus. The present review analyzes published data from the
      ethnomedicinal, phytochemical, and pharmacological studies of plants of the genus
      Markhamia. 

PMID- 27041875
TI  - Biological and Phytopharmacological Descriptions of Litchi Chinensis.
AB  - Plants remain a vital source of drugs and at present, much emphasis is given to
      nutraceuticals. Herbal medicines have been the basis of treatment and cure for
      various diseases and physiological conditions in the traditional methods
      practiced such as ayurveda and homeopathy. Litchi chinensis belongs to the
      Sapindaceae family and is well-known in the Indian traditional system for its
      traditional uses. The parts of the plant used are leaves, flowers, fruits, seed,
      pulp, and pericarp. All parts of the plant are rich sources of phytochemicals-
      epicatechin; procyanidin A2 and procyanidin B2; leucocyanidin; cyanidin
      glycoside, malvidin glycoside, and saponins; butylated hydroxytoluene;
      isolariciresinol; kaempferol; rutin; and stigmasterol. In the present review, we
      explore the lychee's description, traditional medicinal uses, and
      phytoconstituents, and investigate the pharmacological activities in various
      parts of the lychee to show its importance in ethanopharmacology. This is so that
      this review can serve as a ready-to-use material for further research on the
      plant. 

PMID- 27041876
TI  - A Review on Hepatoprotective and Immunomodulatory Herbal Plants.
AB  - The liver is the most important organ that plays an important role in maintaining
      various physiological processes in the body. Hepatitis is an inflammation of the
      liver and is characterized by the presence of inflammatory cells in the tissue of
      the organ. There are five main viruses, referred to as types A, B, C, D, and E.
      These five types are of the greatest concern because of the burden of illness and
      death. Liver injury or liver dysfunction is a major health problem that
      challenges not only health care professionals but also the drug regulatory
      agencies and the pharmaceutical industry. Herbal medicines have been used in the
      treatment of liver disease for a long time. The immune system is the part of body
      that diagnoses the pathogen by using a specific receptor to reveal immediate
      response by the activation of immune components cells, chemokines, and cytokines,
      and also the release of the inflammatory mediator. They potentiate and modulate
      the immune system. The plant-derived phytoconstituents (polysaccharides, proteins
      and flavanoids, lignans, rotenoids, etc.) stimulate the immune system and
      maintained hepatic diseases. There are a number of hepatoprotective and
      immunomodulatory herbs that have been reported. The present review is aimed at
      compiling data on promising phytochemicals from hepatoprotective and
      immunomodulatory herbs. 

PMID- 27041877
TI  - Central or axial atlantoaxial instability: Expanding understanding of
      craniovertebral junction.

PMID- 27041878
TI  - Iatrogeny of Alzheimer's disease: A view point.

PMID- 27041880
TI  - Evaluation of the efficiency of cervical orthoses on cervical fracture: A review
      of literature.
AB  - BACKGROUND: Various methods have been used to stabilize the vertebra in cervical
      fractures, including the use of various orthoses and surgery. However, it is not
      cleared which type of orthosis is more suitable for the subjects with cervical
      fractures to best immobilize the vertebra and to decrease the associated side
      effects. Therefore, the aim of this study was to evaluate the efficiency of
      various orthoses based on the available literature. MATERIALS AND METHODS: A
      search was done in some databases include PubMed, ISI Web of Knowledge, EBSCO,
      Embasco, and Google Scholar. The search was done with some key words such as:
      Cervical spine injuries; odontoid fractures; hangman's fractures; axis fracture;
      axis, atlas, cervical fractures; trauma; neck fracture; neck injury in
      combination with cervical orthoses. The quality of the studies was evaluated by
      use of Downs and Black assessment and Assessment of Multiple Systematic Reviews
      (AMSTAR) for original research and review articles, respectively. RESULTS: Based
      on the aforementioned key words, 25 papers were selected. The quality of the
      studies varies 10-24. Most of the studies were on the use of the halo vest
      orthosis, its side effects and also on complications associated with various
      orthoses. DISCUSSION: Halo orthoses provide a high degree of restriction and
      immobilization; however, there are some side effects associated with this
      orthosis, including swallowing, pin loosening, and infection. It should be
      emphasized that other types of orthoses fewer complications, with reasonable
      outputs on motion restrictions.

PMID- 27041881
TI  - Is atlantoaxial instability the cause of "high" cervical ossified posterior
      longitudinal ligament? Analysis on the basis of surgical treatment of seven
      patients.
AB  - BACKGROUND: Multilevel ossified posterior longitudinal ligaments (OPLLs),
      particularly those that extend into the high cervical region, are formidable and
      challenging surgical problems. The aim of the presentation is to analyze the
      results of surgical treatment of seven consecutive patients having high cervical
      OPLL with atlantoaxial and subaxial facetal fixations. OBJECTIVES: We analyze the
      role of atlantoaxial instability in the management of OPLL that extended into the
      high cervical region, above the lower border of C3 vertebra. MATERIALS AND
      METHODS: All patients in the series were males. The age of the patients ranged 48
      65 years. Clinical evaluation was done by a 5-point clinical grading scale
      described by us, Japanese Orthopedic Association (JOA) score, and visual analog
      scale (VAS). All patients were identified to have relatively "subtle" but
      definite atlantoaxial facetal instability on sagittal imaging and the instability
      was confirmed by direct handling of the facets during surgery. All patients were
      treated by multilevel facetal fixation that included fixation of atlantoaxial
      facets. The aim of surgery was stabilization and arthrodesis of the involved
      spinal segments, as instability was considered to be the prime pathogenetic
      factor of OPLL. Spinal canal decompression, either by anterior corpectomy or
      discoidectomy or by posterior laminectomy or laminoplasty was not done and no
      attempts were made to remove the OPLL. At an average follow-up of 8 months, all
      patients showed progressive symptomatic recovery. CONCLUSION: Atlantoaxial
      facetal instability can be a cause or an association of high cervical OPLL.
      Stabilization of the atlantoaxial joint forms a remarkably effective method of
      treatment.

PMID- 27041879
TI  - Ligamentum flavum hematomas: Why does it mostly occur in old Asian males?
      Interesting point of reported cases: Review and case report.
AB  - Hematoma of the ligamentum flavum (LF) is a rare cause of neural compression and
      sciatica. Currently, the etiology and epidemiological characteristics of
      ligamentum flavum hematoma (LFH) are unknown and epidemiological investigations
      using rewieving of reported cases have not been performed. We report the case of
      a 63-year-old man with a LFH compressing the spinal canal at the left L2-L3
      level, rewieved relevant literature. In Medline research, wefound a total of 50
      reported cases with LFHs, and the interesting point of these cases were analyzed.
      Many of cases were old males. Interestingly, 39 of the 50 cases were reported
      from Asian countries. The ages of 42 patients could be verified. The youngest age
      was 45 years, oldest age was 81 years, and mean age was 66.07 years. Thirty-three
      out of these 42 patients (78.53%) were older than 60 years. An important aspect
      of the present review is to bring attention for occurrence in older Asian males.
      With an increasing number of elderly people in the general population, there is a
      need to investigate risk factors such as sexual gender, age, and geographic
      location for LFH. 

PMID- 27041882
TI  - Diffusion tensor imaging of cervical spinal cord: A quantitative diagnostic tool
      in cervical spondylotic myelopathy.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) is a novel magnetic resonance imaging
      (MRI) technique potentially able to evaluate the microscopic structural
      organization of white matter fibers. AIM: This study aimed to compare fractional
      anisotropy (FA) and apparent diffusion coefficient (ADC) values obtained by DTI
      in stenotic versus nonstenotic cervical spinal segments of patients with clinical
      and neurological evidence of cervical spondylotic myelopathy (CSM). MATERIALS AND
      METHODS: This prospective study included 21 patients with CSM but without T2
      changes on conventional MRI. Diffusion tensor (DT) images from the stenotic and
      nonstenotic segments of the subjects were obtained. FA and ADC values were
      estimated and compared with stenotic versus nonstenotic segments. STATISTICAL
      ANALYSIS: Paired t-test was used [Statistical Package for the Social Sciences
      (SPSS) 12.0]. RESULTS: In the most stenotic segments, the mean FA value was
      significantly lower (0.4228 +/- 0.1090 vs 0.6884 +/- 0.0075, P < 0.001) and the
      mean ADC value was significantly higher (1.312 +/- 0.2405 vs 0.9183 +/- 0.1477, P
      < 0.001) when compared to nonstenotic segments. In addition, there was a negative
      correlation between FA and ADC values (r = 0.63, P = 0.002). CONCLUSIONS: DTI of
      the cervical spine seems to be a promising novel imaging modality in patients
      with CSM. ADVANCES IN KNOWLEDGE: DTI may offer increased diagnostic sensitivity
      as compared to standard MRI and enables earlier detection of the disease.

PMID- 27041883
TI  - Upright magnetic resonance imaging of the lumbar spine: Back pain and
      radiculopathy.
AB  - BACKGROUND: Lumbar back pain and radiculopathy are common diagnoses.
      Unfortunately, conventional magnetic resonance imaging (MRI) findings and
      clinical symptoms do not necessarily correlate in the lumbar spine. With upright
      imaging, disc pathologies or foraminal stenosis may become more salient, leading
      to improvements in diagnosis. MATERIALS AND METHODS: Seventeen adults (10
      asymptomatic and 7 symptomatic volunteers) provided their informed consent and
      participated in the study. A 0.6T upright MRI scan was performed on each adult in
      the seated position. Parameters were obtained from the L2/3 level to the L5/S1
      level including those pertaining to the foramen [cross-sectional area (CSA),
      height, mid-disc width, width, thickness of ligamentum flavum], disc (bulge,
      height, width), vertebral body (height and width), and alignment (lordosis angle,
      wedge angle, lumbosacral angle). Each parameter was compared based on the spinal
      level and volunteer group using two-factor analysis of variance (ANOVA).
      Bonferroni post hoc analysis was used to assess the differences between
      individual spinal levels. RESULTS: Mid-disc width accounted for 56% of maximum
      foramen width in symptomatic volunteers and over 63% in asymptomatic volunteers.
      Disc bulge was 48% greater in symptomatic volunteers compared to asymptomatic
      volunteers. CSA was generally smaller in symptomatic volunteers compared to
      asymptomatic volunteers, particularly at the L4-L5 and L5-S1 spinal levels.
      Thickness of ligamentum flavum (TLF) generally increased from the cranial to
      caudal spinal levels where the L4-L5 and L5-S1 spinal levels were significantly
      thicker than the L1-L2 spinal level. CONCLUSIONS: The data implied that upright
      MRI could be a useful diagnostic option, as it can delineate pertinent
      differences between symptomatic volunteers and asymptomatic volunteers,
      especially with respect to foraminal geometry.

PMID- 27041884
TI  - Factors affecting results of fluoroscopy-guided facet joint injection: Probable
      differences in the outcome of treatment between pure facet joint hypertrophy and
      concomitant diseases.
AB  - STUDY DESIGN: Retrospective cohort study. PURPOSE: Facet joints are considered a
      common source of chronic low-back pain. To determine whether pathogens related to
      the facet joint arthritis have any effect on treatment failure. MATERIALS AND
      METHODS: Facet joint injection was applied to 94 patients treated at our hospital
      between 2011 and 2012 (mean age 59.5 years; 80 women and 14 men). For the purpose
      of analysis, the patients were divided into two groups. Patients who only had
      facet hypertrophy were placed in group A (47 patients, 41 women and 6 men, mean
      age 55.3 years) and patients who had any additional major pathology to facet
      hypertrophy were placed in group B (47 patients, 39 women and 8 men, mean age
      58.9 years). Injections were applied around the facet joint under surgical
      conditions utilizing fluoroscopy device guidance. A mixture of methylprednisolone
      and lidocaine was used as the injection ingredient. RESULTS: In terms of Oswestry
      Disability Index (ODI) and visual analog scale (VAS) scores, no significant
      difference was found between preinjection and immediate postinjection values in
      both groups, and the scores of group A patients were significantly lower (P <
      0.005) compared with that of group B patients at the end of the third, sixth, and
      twelfth month. CONCLUSION: For low-back pain caused by facet hypertrophy, steroid
      injection around the facet joint is an effective treatment, but if there is an
      existing major pathology, it is not as effective.

PMID- 27041885
TI  - Posterolateral instrumented fusion with and without transforaminal lumbar
      interbody fusion for the treatment of adult isthmic spondylolisthesis: A
      randomized clinical trial with 2-year follow-up.
AB  - BACKGROUND: Spondylolisthesis is a common cause of surgery in patients with lower
      back pain. Although posterolateral fusion and pedicle screw fixation are a
      relatively common treatment method for the treatment of spondylolisthesis,
      controversy exists about the necessity of adding interbody fusion to
      posterolateral fusion. The aim of our study was to assess the functional
      disability, pain, and complications in patients with spondylolisthesis treated by
      posterolateral instrumented fusion (PLF) with and without transforaminal lumbar
      interbody fusion (TLIF) in a randomized clinical trial. MATERIALS AND METHODS:
      From February 2007 to February 2011, 50 adult patients with spondylolisthesis
      were randomly assigned to be treated with PLF or PLF+TLIF techniques (25 patients
      in each group) by a single surgeon. Back pain, leg pain, and disability were
      assessed before treatment and until 2 years after surgical treatment using visual
      analog scale (VAS) and oswestry disability index (ODI). Patients were also
      evaluated for postoperative complications such as infection, neurological
      complications, and instrument failure. RESULTS: All patients completed the 24
      months of follow-up. Twenty patients were females and 30 were males. Average age
      of the patients was 53 +/- 11 years for the PLF group and 51 +/- 13 for the PLF +
      TLIF group. Back pain, leg pain, and disability score were significantly improved
      postoperatively compared to preoperative scores (P < 0.001). At 3 months of
      follow-up, there was no statistically significant difference in VAS score for
      back pain and leg pain in both groups; however, after 6 months and 1 year and 2
      years follow-up, the reported scores for back pain and leg pain were
      significantly lower in the PLF+TLIF group (P < 0.05). The ODI score was also
      significantly lower in the PLF+TLIF group at 1 year and 2 years of follow-up (P <
      0.05). One screw breakage and one superficial infection occurred in the PLF+TLIF
      group, which had no statistical significance (P = 0.373). CONCLUSION: It seems
      that accompanying TLIF with PLF might lead to better functional improvement and
      pain reduction in patients with spondylolisthesis.

PMID- 27041886
TI  - Unilateral lag-screw technique for an isolated anterior 1/4 atlas fracture.
AB  - STUDY DESIGN: Fractures of the atlas are classified based on the fracture
      location and associated ligamentous injury. Among patients with atlas fractures
      treated using external immobilization, nonunion of the fracture could be seen.
      OBJECTIVE: Ideally, treatment strategy for an unstable atlas fracture would
      involve limited fixation to maintain the fracture fragments in a reduced position
      without restricting the range of motion (ROM) of the atlantoaxial and
      atlantooccipital joints. SUMMARY OF BACKGROUND DATA: Such a result can be
      established using either transoral limited internal fixation or limited posterior
      lateral mass fixation. However, due to high infection risk and technical
      difficulty, posterior approaches are preferred but none of these techniques can
      fully address anterior 1/4 atlas fractures such as in this case. MATERIALS AND
      METHODS: A novel open and direct technique in which a unilateral lag screw was
      placed to reduce and stabilize a progressively widening isolated right-sided
      anterior 1/4 single fracture of C1 that was initially treated with a rigid
      cervical collar is described. RESULTS: Radiological studies made after the
      surgery showed no implant failure, good cervical alignment, and good reduction
      with fusion of C1. CONCLUSIONS: It is suggested that isolated C1 fractures can be
      surgically reduced and immobilized using a lateral compression screw to allow
      union and maintain both C1-0 and C1-2 motions, and in our knowledge this is the
      first description of the use of a lag screw to achieve reduction of distracted
      anterior 1/4 fracture fragments of the C1 from a posterior approach. This
      technique has the potential to become a valuable adjunct to the surgeon's
      armamentarium, in our opinion, only for fractures with distracted or comminuted
      fragments whose alignment would not be expected to significantly change with
      classical lateral mass screw reduction.

PMID- 27041887
TI  - Minimally invasive space shuttle laminotomy for degenerative lumbar spinal canal
      stenosis.
AB  - STUDY DESIGN: Technical note. OBJECTIVES: To show microsurgical technique,
      considering the meticulous anatomy of the ligamentum flavum (LF). BACKGROUND:
      Different methods are available for treating lumbar spinal canal stenosis (LSCS).
      A minimally invasive surgery, namely, space shuttle laminotomy, has recently been
      proposed. Here, we describe the surgical method for this novel technique. To
      conduct this surgery accurately, surgeons must have perfect knowledge of anatomy,
      especially regarding the LF. MATERIALS AND METHODS AND RESULTS: We use this
      interlaminectomy technique for all cases of LSCS. All patients with LSCS
      recovered from their neurological deficits in shorter hoslital stays than regular
      laminectomy. CONCLUSION: Minimally invasive space shuttle laminotomy (MISSL),
      which involves a microsurgical technique, is a safe, complication-free procedure.

PMID- 27041888
TI  - Recurrent craniospinal epidermoid: A case report.
AB  - We present a rare case of a fourth ventricular epidermoid cyst, which recurred 15
      years after the initial radical tumor resection surgery. The recurrence of the
      tumor extended into the cervical spine. The patient was reoperated and a near
      total excision of both the cranial and spinal components of the epidermoid was
      performed. Our literature search did not reveal any case where there was a
      simultaneous presence of both the cranial and spinal epidermoid tumors. The
      possible cause of extension of the cranial epidermoid into the spinal compartment
      is analyzed. 

PMID- 27041889
TI  - An unusual cause of unilateral facial injuries caused by horseshoe headrest
      during prone positional craniovertebral junction surgery.
AB  - Pressure injuries are an accepted complication of prone positioning during the
      neurosurgical procedures. Horseshoe headrest are intended to reduce the incidence
      and severity of such injuries by allowing limited areas of contact between the
      skin of dependent areas of contact and the supporting surfaces. We report a case
      where a patient positioned prone over a horseshoe headrest developed inadvertent
      unilateral facial pressure injuries following a 6-h long craniovertebral junction
      (CVJ) surgery. We attempt to highlight this complication, analyze its causation,
      and briefly review the existing literature related to similar reported injuries. 

PMID- 27041890
TI  - Extradural spinal meningioma: Revisiting a rare entity.
AB  - Spinal meningiomas are mostly intradural in location although at times these are
      associated with some extradural extensions. Purely extradural spinal meningiomas
      (EDSMs) are however, extremely rare and when present, may cause diagnostic
      dilemma preoperatively. Only seven cases of pure EDSM have been reported till
      date. In this paper, we describe two cases of EDSM affecting the cervical spine
      and present their clinical profiles, radiological findings, operative management,
      and follow-up data, along with a review of the literature. 

PMID- 27041891
TI  - Tiger mosquito - generated devastation in the biosphere!!!

PMID- 27041892
TI  - Comparison of two techniques of harvesting connective tissue and its effects on
      healing pattern at palate and recession coverage at recipient site.
AB  - AIM: To compare the healing pattern in palate following harvestation of
      connective tissue graft by two different techniques and to compare the recession
      coverage at the recipient sites. MATERIALS AND METHODS: 30 recession sites with
      Miller's class I and II recession in 16 patients were recruited for this study.
      Sites were randomly divided into 2 treatment groups. Group I used Unigraft Knife
      to harvest the connective tissue whereas in group II patients Langer & Langer
      techniques was used to harvest the connective tissue graft from the palate.
      Healing was evaluated at the donor site using- wound size(WS), immediate bleeding
      (iB) and delayed bleeding (dB), complete wound epithelialization (CE),
      sensibility disorders (S) and post operative pain (PP) at baseline, 1(st), 4(th),
      and 12(th) week postoperatively. Recession coverage was assessed by measuring
      Clinical Attachment Level (CAL), vertical recession (VR), width of keratinized
      gingiva (KT). RESULTS: On comparison between Group I and II, a statistically
      significant larger wound size was observed in Group I. CWE was higher in Group
      II. A non significant difference was observed when SD, and delayed bleeding were
      compared at all time intervals. A non-significant difference was observed in the
      clinical parameters at the recipient site. CONCLUSION: When evaluating the WS and
      CWE, the Langer and Langer technique was found to be better than the Unigraft
      knife technique for harvesting the connective tissue graft, whereas both the
      techniques were found to be effective in root coverage procedure outcomes.

PMID- 27041893
TI  - Prevalence of molar incisor hypomineralization in 7-9-year-old children of
      Bengaluru City, India.
AB  - BACKGROUND: Molar incisor hypomineralization (MIH) is a developmental defect. The
      prevalence of MIH ranges widely from 2.4% to 40.2%. AIM: This study was under
      taken to determine the prevalence of MIH in 7-9-year-old children of Bengaluru
      City, India. MATERIALS AND METHODS: A cross-sectional epidemiological study was
      conducted in a representative sample of 2500 school children aged 7-9 years of
      Bengaluru, India. Oral examination was carried out by a single trained calibrated
      examiner under natural daylight. RESULTS: Twelve children (0.48%) were diagnosed
      with MIH. A total of 68 teeth were observed with MIH. All four first permanent
      molars were affected in 50% of children. In the molar group, mandibular molars
      (29.41%) were more frequently affected than maxillary molars (27.94%).
      CONCLUSION: The prevalence of MIH in 7-9-year-old children of Bengaluru was
      0.48%, with no gender predilection.

PMID- 27041894
TI  - Effect of dentin dehydration and composite resin polymerization mode on bond
      strength of two self-etch adhesives.
AB  - BACKGROUND: Dual-cured composite resins are similar to self-cured composite
      resins in some of their clinical applications due to inadequate irradiation, lack
      of irradiation, or delayed irradiation. Therefore, incompatibility with self-etch
      adhesives (SEAs) should be taken into account with their use. On the other, the
      extent of dentin dehydration has a great role in the quality of adhesion of these
      resin materials to dentin. The aim of this study was to investigate the effect of
      dentin dehydration and composite resin polymerization mode on bond strength of
      two SEAs. MATERIALS AND METHODS: A total of 120 dentinal specimens were prepared
      from extracted intact third molars. Half of the samples were dehydrated in
      ethanol with increasing concentrations. Then Clearfil SE Bond (CSEB) and Prompt L
      Pop (PLP) adhesives were applied in the two groups. Cylindrical composite resin
      specimens were cured using three polymerization modes: (1) Immediate light
      curing, (2) delayed light-curing after 20 min, and (3) self-curing. Bond strength
      was measured using universal testing machine at a crosshead speed of 1 mm/min.
      Data were analyzed with two-way ANOVA and Duncan post hoc tests. Statistical
      significance was defined at P < 0.05. RESULTS: There were no significant
      differences for CSEB subgroups with hydrated and dehydrated dentin samples
      between the three different curing modes (P > 0.05). PLP showed significant
      differences between subgroups with the lowest bond strength in hydrated dentin
      with delayed light-curing and self-cured mode of polymerization. CONCLUSION:
      Within the limitations of this study, a delay in composite resin light-curing or
      using chemically cured composite resin had a deleterious effect on dentin bond
      strength of single-step SEAs used in the study.

PMID- 27041895
TI  - Can bone marrow aspirate concentrate change the mineralization pattern of the
      anterior maxilla treated with xenografts? A preliminary study.
AB  - OBJECTIVE: To evaluate bony reconstruction of the atrophic anterior maxilla using
      particulate grafts with or without autologous bone marrow aspirate concentrate
      (BMAC). MATERIALS AND METHODS: Eight patients with atrophy of the anterior
      maxilla due to teeth loss were selected and split into groups according to the
      type of material used: Control Group (CG) (n = 4) - particulate xenograft only
      and Test Group (TG) (n = 4) - a combination of particulate xenograft and BMAC.
      Both groups received a collagen membrane to cover the xenograft. After 4 months,
      during implant placement, a sample of bone was removed from the graft area using
      a 2 mm diameter trephine bur. The specimens were fixed and preserved for
      histomorphometric evaluation, which included the following parameters:
      Mineralized tissue (MT) and non-MT (NMT). Cone beam computed tomography was
      performed at 3 time intervals to measure bone thickness: (1) Before grafting, (2)
      4 months and (3) 8 months postgrafting, using localized bone gain (mm) as the
      outcome variable. RESULTS: Tomographic analysis revealed bone gain in CG of 3.78
      +/- 1.35 mm and 4.34 +/- 1.58 mm at 4 and 8 months, respectively. TG showed an
      increase of 3.79 +/- 0.52 mm and 4.09 +/- 1.33 mm after 4 and 8 months,
      respectively. Histomorphometric analysis revealed that, for CG, MT- and NMT
      related values were 52.3% +/- 16.78% and 47.70% +/- 5.55%, respectively, whereas
      for TG, they were 65.04% +/- 20.98% and 34.96 +/- 10.38, respectively.
      CONCLUSION: Although radiographic bone gain appeared similar between the groups,
      the use of BMAC obtained via the BMAC((r)) method revealed an increased
      mineralization trend in the anterior maxilla. It must be highlighted, however,
      that this is a preliminary study with a relatively small sample population and
      further studies with larger sample sizes are needed to verify these results.

PMID- 27041896
TI  - Effect of various chemical agents used in gingival retraction systems on smear
      layer: Scanning electron microscope study.
AB  - BACKGROUND: Chemical agents used for gingival retraction affects the smear layer.
      AIM: To determine the effect of three different chemical agents used for gingival
      retraction systems on smear layer. MATERIALS AND METHODS: Four human premolars
      were prepared using air-rotor with air-water spray to receive full crown
      restoration. Three of them were treated with 21.3% aluminum chloride for 10 min,
      0.05% oxymetazoline hydrochloride for 10 min, and expasyl for 2 min,
      respectively. One sample was left untreated. Then, the tooth specimens were
      rinsed with tap water to remove any residue of test materials. All the samples
      (treated and untreated) were processed by scanning electron microscope (SEM).
      Processed samples were examined under SEM at *2400 to evaluate the effect of
      chemical agents on smear layer. RESULTS: SEM examination revealed that 0.05%
      oxymetazoline hydrochloride for 10 min produced no alteration to smear layer
      followed by minimum alteration by expasyl for 2 min and complete removal of smear
      layer with etching of dentin with 21.3% aluminum chloride for 10 min. CONCLUSION:
      0.05% oxymetazoline hydrochloride and expasyl are kind to smear layer.

PMID- 27041897
TI  - Volumetric changes in pharyngeal airway in Class II division 1 patients treated
      with Forsus-fixed functional appliance: A three-dimensional cone-beam computed
      tomography study.
AB  - OBJECTIVE: Recent years have witnessed a renewed interest to determine a
      quantifiable relationship between mandibular advancement performed with an
      orthodontic appliance and the resulting airway volume. The study was conducted to
      evaluate the volumetric changes in pharyngeal airway space using cone-beam
      computed tomography (CBCT) in Class II division 1 patients with retrognathic
      mandible treated by Forsus-fixed functional appliance and to compare them with
      their pretreatment findings. MATERIALS AND METHODS: Thirty patients with Class II
      division 1 malocclusion of age group 10-17 years were selected randomly and
      evaluated for changes in pharyngeal airway volume with and without Forsus-fixed
      functional appliance. Patients in each group underwent CBCT scan of head and neck
      region at pretreatment stage and 6 months after the initial scan. Institutional
      approval for the project was obtained from the Ethical Committee. Volumetric
      changes of upper (oropharynx) and lower (hypopharynx) pharyngeal airways were
      measured on scanogram using computer software and intragroup comparisons were
      done. RESULTS: There was a statistically significant increase in the volume of
      both hypopharynx and oropharynx and also total airway volume in patients treated
      with Forsus-fixed functional appliance. Three-dimensional reconstruction of the
      airway also demonstrates a considerable increase in pharyngeal airway space.
      CONCLUSION: Forsus-fixed functional appliance can be a promising appliance for
      improving pharyngeal airway volume in Class II division 1 patients with
      retrognathic mandible thus preventing obstructive sleep apnea and other
      respiratory problems in future. However, the long-term implications of this
      treatment modality need further consideration and a longer period of follow-up.

PMID- 27041898
TI  - Effect of palatal form on movement of teeth during processing of complete denture
      prosthesis: An in-vitro study.
AB  - AIM: The aim of this in-vitro study was to assess the influence of shallow and
      deep palatal forms on the movement of teeth during the processing of complete
      denture prosthesis. MATERIALS AND METHODS: Maxillary casts with shallow and deep
      palatal forms were selected and duplicated to make 10 casts of each palatal form.
      Base plates were constructed and teeth were arranged in their anatomic positions.
      Metal pins with true apex were placed on the central groove of the right and left
      first molars and one on the incisive papilla area as a reference point. Casts
      were scanned using i-CAT Vision Q 1.9 (i-CAT cone beam 3D dental imaging system
      by Imaging Sciences International, PA, USA), which has 360 degrees  rotational
      tomography. The distances between the apices of metallic pin inserts on the teeth
      and fitted point of reference were recorded in buccopalatal axes at waxed up
      stage, after deflasking, and after finishing and polishing. RESULTS: Results
      showed a statistically significant movement of teeth in shallow and deep palatal
      forms during all stages of complete denture processing. In shallow palatal form
      dentures, there was a significant tooth movement in palatal direction between
      Stages 1 and 2 (P <= 0.05) and buccal movement between Stages 2 and 3. In deep
      palatal form dentures, teeth showed a statistically significant (P <= 0.05)
      movement in buccal direction during all stages of denture processing. CONCLUSION:
      Teeth showed significant movement during processing of acrylic resin dentures.
      Overall, the movement of teeth in shallow palatal form dentures was in palatal
      direction, whereas in deep palatal form dentures, the movement of teeth was in
      buccal direction.

PMID- 27041899
TI  - Extraction protocols for orthodontic treatment: A retrospective study.
AB  - BACKGROUND AND OBJECTIVES: Various extraction protocols have been followed for
      successful orthodontic treatment. The purpose of this study was to evaluate the
      extraction protocols in patients who had previously undergone orthodontic
      treatment and also who had reported for continuing orthodontic treatment from
      other clinics. MATERIALS AND METHODS: One hundred thirty eight patients who
      registered for orthodontic treatment at the Faculty of Dentistry were divided
      into 10 extraction protocols based on the Orthodontic treatment protocol given by
      Janson et al. and were evaluated for statistical significance. RESULTS: The
      descriptive statistics of the study revealed a total of 40 (29%) patients in
      protocol 1, 43 (31.2%) in protocol 2, 18 (13%) in protocol 3, 16 (11.6%) in
      protocol 5, and 12 (8.7%) in Type 3 category of protocol 9. The Type 3 category
      in protocol 9 was statistically significant compared to other studies. Midline
      shift and collapse of the arch form were noticed in these individuals.
      CONCLUSION: Extraction of permanent teeth such as canine and lateral incisors
      without rational reasons could have devastating consequences on the entire
      occlusion. The percentage of cases wherein extraction of permanent teeth in the
      crowded region was adopted as a treatment option instead of orthodontic treatment
      is still prevalent in dental practice. The shortage of orthodontists in Malaysia,
      the long waiting period, and lack of subjective need for orthodontic treatment at
      an earlier age group were the reasons for the patient's to choose extraction of
      the mal-aligned teeth such as the maxillary canine or maxillary lateral incisors.

PMID- 27041900
TI  - In vivo comparison of cavity disinfection efficacy with APF gel, Propolis, Diode
      Laser, and 2% chlorhexidine in primary teeth.
AB  - BACKGROUND: The survival of atraumatic restorative treatment (ART) restorations
      would be enhanced if near total elimination of cariogenic microorganisms could be
      done in the process of cavity cleaning before placing a restoration. Thus, use of
      disinfecting agents for achieving this goal could herald a new beginning in the
      field of contemporary dentistry. AIM: To assess and compare the cavity
      disinfection efficacy of APF gel, Brazilian Propolis, Diode Laser, and 2%
      chlorhexidine (CHX). MATERIALS AND METHODS: The study was a randomized, single
      blinded, parallel grouped, active controlled trial. Eighty primary molars in 68
      children with cavitated dentinal occlusal caries were randomly assigned into four
      groups (20 teeth each) Group I: APF gel; Group II: Propolis; Group III: Diode
      Laser, and Group IV: 2% CHX (control). After cavity preparation using ART
      procedure, dentinal samples collected before and after disinfection with
      respective agent of the group. These samples were subjected to microbiological
      evaluation, for total viable count (TVC) on blood agar, Streptococcus mutans on
      mutans-sanguis (MS) agar, and Lactobacilli (LB) on Rogosa agar. RESULTS:
      Intragroup comparison (Wilcoxon signed rank test) showed significant reductions
      in TVC, MS, and LB counts in all the groups. Pairwise Mann-Whitney test showed
      APF gel had least bacterial reductions among the agents tested. CONCLUSION: This
      study illustrated the need for cavity disinfection. Diode Laser and Brazilian
      Propolis are equally effective as 2% CHX in cavity disinfection.

PMID- 27041901
TI  - Efficacy of ozonized olive oil in the management of oral lesions and conditions:
      A clinical trial.
AB  - The oral cavity is an open ecosystem that shows a dynamic balance between the
      entrance of microorganisms (bacterial, viral or fungal), colonization modalities,
      nutritional balance, and host defenses against their removal. The oral lesions
      including aphthous ulcerations, herpes labialis, oral candidiasis, oral lichen
      planus, and angular cheilitis some of the common entities encountered in the
      clinical practice. A variety of treatment options is available in the literature
      for all of these lesions and conditions. Topical ozone therapy is a minimally
      invasive technique that can be used for these conditions without any side
      effects. AIM AND OBJECTIVES: To evaluate the efficacy of ozonized olive oil in
      the treatment of oral lesions and conditions. MATERIALS AND METHODS: A
      longitudinal study was carried out on 50 patients (aphthous ulcerations, herpes
      labialis, oral candidiasis, oral lichen planus, and angular cheilitis). The
      ozonized olive oil was applied twice daily until the lesion regresses for a
      maximum of 6 months. RESULTS: All the lesions regress in patients with aphthous
      ulcerations, herpes labialis, oral candidiasis and angular cheilitis or showed
      improvement in the signs and symptoms in oral lichen planus patients. No toxicity
      or side effect was observed in any of the patients. CONCLUSION: Ozone therapy
      though requires a gaseous form to be more effective, but topical form can also
      bring out the positive results without any toxicity or side effect. Hence, it can
      be considered as a minimally invasive therapy for the oral infective and
      immunological conditions.

PMID- 27041902
TI  - Comparative evaluation of pressure generated on a simulated maxillary oral analog
      by impression materials in custom trays of different spacer designs: An in vitro
      study.
AB  - INTRODUCTION: Literature reveals that masticatory load on denture bearing tissues
      through complete dentures should be maximum on primary stress bearing areas and
      least on relief area in accordance with the histology of underlying tissues. A
      study to validate the existing beliefs was planned to compare the pressure on
      mucosa using selective pressure technique and minimal pressure technique, with
      the incorporation of two different impression materials utilizing the pressure
      sensors during secondary impression procedure. MATERIALS AND METHODS: The study
      was performed using a maxillary analog. Three pressure sensors were imbedded in
      the oral analog, one in the mid palatine area and the other two in the right and
      left ridge crest. Custom trays of two different configurations were fabricated.
      The two impression materials tested were light body and zinc oxide eugenol. A
      total of 40 impressions were made. A constant weight of 1 kg was placed, and the
      pressure was recorded as initial and end pressures. RESULTS: A significant
      difference in the pressure produced using different impression materials was
      found (P < 0.001). Light body vinyl polysiloxane produced significantly lesser
      pressure than zinc oxide eugenol impression materials. The presence of relief did
      affect the magnitude of pressure at various locations. CONCLUSION: All impression
      materials produced pressure during maxillary edentulous impression making. Tray
      modification is an important factor in changing the amount of pressure produced.
      The impression materials used also had a significant role to play on the
      pressures acting on the tissues during impression procedure. CLINICAL
      IMPLICATION: Light body VPS impression material may be recommended to achieve
      minimal pressure on the denture bearing tissues in both selective as well as
      minimal pressure techniques.

PMID- 27041903
TI  - Sella size and jaw bases - Is there a correlation???
AB  - INTRODUCTION: Sella turcica is an important cephalometric structure and attempts
      have been made in the past to correlate its dimensions to the malocclusion.
      However, no study has so far compared the size of sella to the jaw bases that
      determine the type of malocclusion. The present study was undertaken to find out
      any such correlation if it exists. MATERIALS AND METHODS: Lateral cephalograms of
      110 adults consisting of 40 Class I, 40 Class II, and 30 Class III patients were
      assessed for the measurement of sella length, width, height, and area. The
      maxillary length, mandibular ramus height, and body length were also measured.
      The sella dimensions were compared among three malocclusion types by one-way
      ANOVA. Pearson correlation was calculated between the jaw size and sella
      dimensions. Furthermore, the ratio of jaw base lengths and sella area were
      calculated. RESULTS AND CONCLUSION: Mean sella length, width and area were found
      to be greatest in Class III, followed by Class I and least in Class II though the
      results were not statistically significant. 3 out of 4 measured dimensions of
      sella, correlated significantly with mandibular ramus and body length each.
      However, only one dimension of sella showed significant correlation with maxilla.
      The mandibular ramus and body length show a nearly constant ratio to sella area
      (0.83-0.85, 0.64-0.65, respectively) in all the three malocclusions. Thus,
      mandible has a definite and better correlation to the size of sella turcica.

PMID- 27041904
TI  - Endodontic management of nonvital permanent teeth having immature roots with one
      step apexification, using mineral trioxide aggregate apical plug and autogenous
      platelet-rich fibrin membrane as an internal matrix: Case series.
AB  - A tooth with blunderbuss canal and open apex can be an endodontic challenge
      because of difficulty in obtaining an apical seal, and existing thin radicular
      walls which are susceptible to fracture. To overcome the limitations of
      traditional long-term calcium hydroxide apexification procedures, nonsurgical one
      step apexification using an array of materials such as mineral trioxide aggregate
      (MTA) has been suggested. However, adequate compaction of MTA in teeth with wide
      open apices can be an arduous task, and an internal matrix is required for
      controlled placement of MTA against which obturating material can be condensed.
      Platelet-rich fibrin (PRF), a second generation platelet concentrate containing
      several growth factors that promotes hard and soft-tissue healing, has been used
      as an internal matrix to create an apical plug of MTA and hence prevent extrusion
      of filling materials. This case series presents the endodontic management of
      immature permanent teeth with open apices using internal matrix of autologous PRF
      membrane and one step apical barrier placement of MTA. 

PMID- 27041905
TI  - Central myofibroma of the maxilla.
AB  - Myofibroma is a rare benign localized or generalized proliferation of
      myofibroblastic tissue occurring mostly in infants or children. In the oral
      region, most lesions occur in the mandible, lip, buccal mucosa, and tongue;
      however, the lesions arising in the maxilla are very rare. Myofibroma has an
      aggressive clinical presentation and is often treated aggressively because of an
      inappropriate diagnosis. A unique feature of central myofibroma of the jaws is
      the potential for teeth and other odontogenic structures to be involved by tumor.
      We report a case of myofibroma arising in the left side of the maxilla of a 12
      year-old girl and describe the differential diagnosis from other spindle cell
      lesions of neural and smooth muscle origin. We treated the case using surgical
      excision under general anesthesia. Immunohistochemical staining was done for
      establishing the diagnosis since histopathological diagnosis with conventional
      staining could not distinguish myofibroma from spindle cell tumors. 

PMID- 27041906
TI  - Successful treatment of Class II malocclusion with bidental protrusion using
      standard edgewise prescription.
AB  - This case report deals with the successful orthodontic treatment of a 14-year-old
      female patient having Class II malocclusion with bidental protrusion using
      standard edgewise prescription. She reported with forwardly placed upper front
      teeth and difficulty in closing lips. She had prognathic maxilla, retrognathic
      mandible, and full cusp Class II molar and canine relation bilaterally with
      overjet of 7 mm. She was in cervical vertebrae maturation indicator Stage IV. The
      case was treated by fixed extraction mechanotherapy. Interarch Class II mechanics
      was used to retract the upper incisor and to mesialize the lower molars.
      Simultaneously, Class I mechanics was used to upright lower incisors. Tip back
      bend, curve of Spee, and extra palatal root torque were incorporated in upper
      archwire to maintain molars in upright position and prevent extrusion and
      deepening of bite, respectively. There was satisfactory improvement in facial
      profile at the end of 24 months. After a follow-up of 6 months, occlusion was
      stable. 

PMID- 27041907
TI  - Mandibular incisive canal in relation to periapical surgery.
AB  - The aim of the present paper is to emphasize the importance of the mandibular
      interforaminal neurovascular bundle with a case and make a warning to dentists
      and surgeons during oral and maxillofacial surgeries, such as implant
      replacement, bone harvesting, genioplasty, open reduction of a mandibular
      fracture, and cyst enucleations at this region. In this paper, we present a 58
      year-old male who referred with pain and a tingling sensation on the left lower
      lip. After radiographical, extraoral and intraoral examinations, findings
      indicated the lesion to be a cyst which was related with a periapical lesion of
      the canine tooth and extracted socket of first premolar tooth. After removal of a
      cyst, the mandibular incisive nerve was documented which was in relation to cyst
      cavity. 

PMID- 27041908
TI  - Correction of an adult Class II division 2 individual using fixed functional
      appliance: A noncompliance approach.
AB  - This case report describes the application of fixed functional appliance in the
      treatment of an adult female having Class II division 2 malocclusion with
      retroclination of upper incisors. Fixed functional appliance was used to correct
      the overjet after the uprighting of upper incisors. Fixed functional appliance
      was fitted on a rigid rectangular arch wire. Application of fixed functional
      appliance achieved a good Class I molar relationship along with Class I canine
      relationship with normal overjet and overbite. Fixed functional appliance is
      effective in the treatment of Class II malocclusions, even in adult patients, and
      can serve as an alternate choice of treatment instead of orthognathic surgery.
      This is a case; wherein, fixed functional appliance was successfully used to
      relieve deep bite and overjet that was ensued after leveling and aligning. We
      demonstrate that fixed functional appliance can act as a "noncompliant corrector"
      and use of Class II elastics can be avoided. 

PMID- 27041909
TI  - Primary malignant melanoma of oral cavity: A report of three rare cases.
AB  - Oral malignant melanoma (OMM) is a rare tumor of melanocytic origin, accounting
      for 20-30% of malignant melanomas at the mucosal surface and 16% intra-orally.
      Hard palate and maxillary gingiva are the most common involved sites. In this
      case series, we present varying patterns of presentation of three cases of OMM
      with one case of distant metastasis. All cases in the current series presented at
      an advanced stage and died within a year of diagnosis. In conclusion, due to the
      aggressive clinical course and poor prognosis of this deadly lesion, it is of
      paramount importance to maintain a high index of suspicion for early detection
      and diagnosis for any pigmented lesion in the oral cavity. 

PMID- 27041910
TI  - Hybrid ameloblastoma: An amalgam of rare and conventional ameloblastoma.
AB  - Ameloblastoma is a common benign odontogenic tumor with multiple histologic
      types. This case report describes an unusual type of ameloblastoma called "Hybrid
      Ameloblastoma" with features of both follicular and desmoplastic ameloblastoma in
      a 50-year-old female. This is a very rare form of ameloblastoma as <30 cases have
      been reported so far in literature. Though this rare form of ameloblastoma is
      only a histologic variant, it poses a great challenge to diagnosticians and thus
      to surgeons as there will be mismatch of biopsy reports at different sites in the
      same tumor thereby changing the treatment plan. This case report is one such
      example of diverse presentation of this ameloblastoma with conflicting
      histopathological diagnosis at initial biopsy and on surgical excision. 

PMID- 27041911
TI  - Pindborg tumor.
AB  - Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is
      a rare odontogenic epithelial neoplasm. So far, nearly 200 cases have been
      reported in the literature. We are reporting a case of CEOT in a 42-year-old male
      patient with painless bony swelling in the mandible. The clinical, radiographic,
      and histopathologic features are discussed with relevant references. 

PMID- 27041912
TI  - Management of skeletal Class III malocclusion with face mask therapy and
      comprehensive orthodontic treatment.
AB  - Orthopedic correction of skeletal Class III malocclusion in a growing patient is
      crucial as it can circumvent future surgical procedures. Further, as surgery is
      done only at a later stage, early treatment helps to avoid the detrimental
      effects produced by the facial disfigurement on the patient's social life. This
      case report describes the treatment of a child aged 9 years 6 months who had a
      skeletal Class III malocclusion. The treatment plan involved the use of a reverse
      pull headgear (facemask) and multibracket appliance therapy resulting in
      successful correction of the malocclusion. The treatment results were highly
      satisfactory resulting in improved facial esthetics, a skeletal Class I with a
      Dental Class I molar and canine relationship, an ideal overjet and overbite.
      Thus, dentoalveolar camouflage, if done in properly selected cases, alleviates
      the need for surgical intervention. The patient is being monitored until the end
      of growth to ensure the stability of treatment results. 

PMID- 27041913
TI  - Orthodontic management of a borderline case with ectopic maxillary canine by
      unilateral premolar extractions.
AB  - Management of orthodontic cases often requires extraction of permanent teeth. The
      decision making regarding extractions depends upon the arch length tooth material
      discrepancies, the growth pattern, general profile, and arch asymmetries. Unique
      orthodontic problems may command special treatment lines to be taken. The present
      report describes a case with unilateral buccally blocked out canine and bilateral
      posterior crossbite, for which unilateral premolar extractions were performed
      achieve esthetic and functionally stable occlusion. 

PMID- 27041914
TI  - Dilated odontoma: A report of two cases from a radiological perspective.
AB  - Dilated odontoma is the most extreme form of dens invaginatus. The lesion appears
      as a roughly spherical mass that does not resemble a tooth but in a way appears
      tooth - like on radiographs due to somewhat similar radiodensity. The lesion is
      mostly spherical in appearance and hence the term "dilated." Occasionally, we
      come across cases of simultaneous pathologies. Here, we report two cases of a
      dilated odontoma one of which is associated with dentigerous cyst and in other
      case dilated odontoma pushing the maxillary sinus superiorly. Histologically, the
      mass was composed of dentinal tubules. These morphological and histological
      features are compatible with those of a dilated odontoma. 

PMID- 27041915
TI  - Aneurysmal bone cyst of maxillary alveolus: A rare case report.
AB  - Aneurysmal bone cyst (ABC) is a nonneoplastic rare pathologic entity of the jaws.
      Its locally aggressive nature and high recurrence rate after curettage make
      surgical resection a better treatment option. Here, we present a case of ABC of
      maxillary alveolus and its management by alveolectomy followed by white head
      varnish pack application in the surgical defect. 

PMID- 27041916
TI  - Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate
      as first clinical manifestation of acquired immune deficiency syndrome.
AB  - Anaplastic large cell lymphoma (ALCL) is an uncommon disease, accounting for <5%
      of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who
      presented a clinically benign swelling in the right anterior palatal region since
      last 2 months. Radiographic evaluation showed no bone loss in palatal area.
      Histological and radiological examination was in favor of a peripheral reactive
      lesion like pyogenic granuloma or a benign salivary gland tumor.
      Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase
      negative (ALK(-)) ALCL. Further laboratory tests ELISA for human immunodeficiency
      virus (HIV) and CD4 cell count was done which showed positivity for HIV. To the
      best of our knowledge, it is the first case of ALK(-) ALCL in the hard palate
      presenting as the first clinical manifestation of acquired immune deficiency
      syndrome. 

PMID- 27041917
TI  - A novel speech prosthesis for mandibular guidance therapy in hemimandibulectomy
      patient: A clinical report.
AB  - Treating diverse maxillofacial patients poses a challenge to the maxillofacial
      prosthodontist. Rehabilitation of hemimandibulectomy patients must aim at
      restoring mastication and other functions such as intelligible speech,
      swallowing, and esthetics. Prosthetic methods such as palatal ramp and mandibular
      guiding flange reposition the deviated mandible. Such prosthesis can also be used
      to restore speech in case of patients with debilitating speech following surgical
      resection. This clinical report gives detail of a hemimandibulectomy patient
      provided with an interim removable dental speech prosthesis with composite resin
      flange for mandibular guidance therapy. 

PMID- 27041918
TI  - Erratum: Dental management of hypohidrotic ectodermal dysplasia: A report of two
      cases.
AB  - [This corrects the article on p. 414 in vol. 6, PMID: 26321846.]. 

PMID- 27041919
TI  - Erratum: Christ Siemens Touraine syndrome: Two case reports and felicitous
      approaches to prosthetic management.
AB  - [This corrects the article on p. 274 in vol. 6, PMID: 26097372.]. 

PMID- 27041920
TI  - Retraction: Prosthetic rehabilitation of edentulous patient with limited oral
      access: A clinical report.
AB  - [This retracts the article on p. 349 in vol. 3, PMID: 23293498.]. 

PMID- 27041921
TI  - Retraction: The effect of using different rinsing angles on the micro tensile
      bond strength of the sealant to the etched enamel.
AB  - [This retracts the article on p. 67 in vol. 5, PMID: 24808698.]. 

PMID- 27041922
TI  - National cancer incidence and mortality in China, 2012.
AB  - BACKGROUND: Population-based cancer registration data in 2012 from all available
      cancer registries were collected by the National Central Cancer Registry (NCCR).
      NCCR estimated the numbers of new cancer cases and cancer deaths in China with
      compiled cancer incidence and mortality rates. METHODS: In 2015, there were 261
      cancer registries submitted cancer incidence and deaths occurred in 2012. All the
      data were checked and evaluated based on the NCCR criteria of data quality.
      Qualified data from 193 registries were used for cancer statistics analysis as
      national estimation. The pooled data were stratified by area (urban/rural),
      gender, age group [0, 1-4, 5-9, 10-14, ..., 85+] and cancer type. New cancer
      cases and deaths were estimated using age-specific rates and corresponding
      national population in 2012. The Chinese census data in 2000 and Segi's
      population were applied for age-standardized rates. All the rates were expressed
      per 100,000 person-year. RESULTS: Qualified 193 cancer registries (74 urban and
      119 rural registries) covered 198,060,406 populations (100,450,109 in urban and
      97,610,297 in rural areas). The percentage of cases morphologically verified
      (MV%) and death certificate-only cases (DCO%) were 69.13% and 2.38%,
      respectively, and the mortality to incidence rate ratio (M/I) was 0.62. A total
      of 3,586,200 new cancer cases and 2,186,600 cancer deaths were estimated in China
      in 2012. The incidence rate was 264.85/100,000 (289.30/100,000 in males,
      239.15/100,000 in females), the age-standardized incidence rates by Chinese
      standard population (ASIRC) and by world standard population (ASIRW) were
      191.89/100,000 and 187.83/100,000 with the cumulative incidence rate (0-74 age
      years old) of 21.82%. The cancer incidence, ASIRC and ASIRW in urban areas were
      277.17/100,000, 195.56/100,000 and 190.88/100,000 compared to 251.20/100,000,
      187.10/100,000 and 183.91/100,000 in rural areas, respectively. The cancer
      mortality was 161.49/100,000 (198.99/100,000 in males, 122.06/100,000 in
      females), the age-standardized mortality rates by Chinese standard population
      (ASMRC) and by world standard population (ASMRW) were 112.34/100,000 and
      111.25/100,000, and the cumulative mortality rate (0-74 years old) was 12.61%.
      The cancer mortality, ASMRC and ASMRW were 159.00/100,000, 107.231/100,000 and
      106.13/100,000 in urban areas, 164.24/100,000, 118.22/100,000 and 117.06/100,000
      in rural areas, respectively. Cancers of lung, stomach, liver, colorectum,
      esophagus, female breast, thyroid cervix, brain tumor and pancreas were the most
      common cancers, accounting for about 77.4% of all cancer new cases. Lung cancer,
      liver cancer, stomach cancer, esophageal cancer, colorectal cancer, pancreatic
      cancer, female breast cancer, brain tumor, leukemia and lymphoma were the leading
      causes of cancer death, accounting for about 84.5% of all cancer deaths. The
      cancer spectrum showed difference between urban and rural, males and females both
      in incidence and mortality rates. CONCLUSIONS: Cancer surveillance information in
      China is making great progress with the increasing number of cancer registries,
      population coverage and the improving data quality. Cancer registration plays a
      fundamental role in cancer control by providing basic information on population
      based cancer incidence, mortality, survival and time trend. The disease burden of
      cancer is serious in China, so that, cancer prevention and control, including
      health education, health promotion, cancer screening and cancer care services in
      China, should be enhanced.

PMID- 27041923
TI  - A phase I study of nimotuzumab plus docetaxel in chemotherapy
      refractory/resistant patients with advanced non-small-cell lung cancer.
AB  - BACKGROUND: To determine the safety and therapeutic efficacy of nimotuzumab (h
      R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC)
      patients who have failed to respond to prior first-line chemotherapy. METHODS: In
      this single-center, open-label, dose-escalating phase I trial, patients with
      epidermal growth factor receptor (EGFR)-expressing stage IV NSCLC were treated
      with nimotuzumab plus docetaxel according to a dose escalation schedule. The
      safety and efficacy of the combination treatment were observed and analyzed.
      RESULTS: There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The
      dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest
      administration of study drug was 40 weeks at the 600 mg/week dose level. Grade
      III-IV toxicities included neutropenia and fatigue, and other toxicities included
      rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose
      level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose
      level of nimotuzumab. No objective responses were observed, and stable disease
      was observed in eight patients (66.7%). The median progression-free survival
      (PFS) was 4.4 months in all patients, 1.3 months in patients with the EGFR
      mutation, and 4.4 months in those with wild type EGFR (EGFR WT). The median
      survival time (MST) was 21.1 months in all patients, 21.1 months in patients with
      EGFR mutation, and 26.4 months in patients with EGFR WT. CONCLUSIONS: Nimotuzumab
      and docetaxel combination therapy was found to be well tolerated and efficacious.
      Further study of nimotuzumab is warranted in advanced NSCLC patients.

PMID- 27041924
TI  - Heat shock protein inhibitor, quercetin, as a novel adjuvant agent to improve
      radiofrequency ablation-induced tumor destruction and its molecular mechanism.
AB  - BACKGROUND: We investigated the effect of a small molecular inhibitor of heat
      shock protein (HSP), quercetin, on tumor radiofrequency (RF) ablation, and
      explored the underlying molecular mechanisms. METHODS: In in vivo study, rats
      with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross
      coagulation areas were compared, and next, randomized into four treatment arms
      (control, quercetin alone, RF alone, and combination) for Kaplan-Meier analysis
      of defined endpoint survival. Then the distribution and expression levels of heat
      shock protein 70 (HSP70), cleaved caspase-3 and heat shock factor 1 (HSF1) were
      analyzed after different treatments. In in vitro study, we used quercetin to
      promote SK-HEP-1 (hepatic) and MCF-7 (breast) cancer cell apoptosis in heat shock
      cell model, and siRNA was used to block c-Jun and to explore the role of
      activating protein-1 (AP-1) signaling pathways. RESULTS: We found the effects of
      quercetin plus RFA resulted in increase on the tumor destruction/endpoint
      survival (26.5+/-3.4 d) in vivo, compared with RF alone (17.6+/-2.5 d) and
      quercetin alone (15.7+/-3.1 d). Most importantly, quercetin-induced cancer cell
      death required the presence of HSF1 in animal model. Furthermore, quercetin
      directly down-regulated expression of HSF1 in vitro, which our findings have
      revealed, required the activation of AP-1 signaling pathways by loss-of-function
      analysis using siRNA mediated targeting of c-Jun. CONCLUSIONS: These results
      indicated a protective role of quercetin in tumor ablation and highlighted a
      novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid
      tumors.

PMID- 27041926
TI  - The update of prostatic ductal adenocarcinoma.
AB  - Since initially described in 1967, prostatic ductal adenocarcinoma (PDA) has
      engendered a series of controversies on its origin, histological features, and
      biological behavior. Owing to the improvement of molecular biological technique,
      there are some updated findings on the characteristics of PDA. In the current
      review, we will mainly analyze its origin, clinical manifestations, morphological
      features, differential diagnosis, immunophenotype and molecular genetics, with
      the purpose of enhancing recognition of this tumor and making a correct diagnosis
      and treatment choice. 

PMID- 27041927
TI  - The evolving Gleason grading system.
AB  - The Gleason grading system for prostate adenocarcinoma has evolved from its
      original scheme established in the 1960s-1970s, to a significantly modified
      system after two major consensus meetings conducted by the International Society
      of Urologic Pathology (ISUP) in 2005 and 2014, respectively. The Gleason grading
      system has been incorporated into the WHO classification of prostate cancer, the
      AJCC/UICC staging system, and the NCCN guidelines as one of the key factors in
      treatment decision. Both pathologists and clinicians need to fully understand the
      principles and practice of this grading system. We here briefly review the
      historical aspects of the original scheme and the recent developments of Gleason
      grading system, focusing on major changes over the years that resulted in the
      modern Gleason grading system, which has led to a new "Grade Group" system
      proposed by the 2014 ISUP consensus, and adopted by the 2016 WHO classification
      of tumours of the prostate. 

PMID- 27041925
TI  - Molecular genetics and immunohistochemistry characterization of uncommon and
      recently described renal cell carcinomas.
AB  - Renal cell carcinoma (RCC) compromises multiple types and has been emerging
      dramatically over the recent several decades. Advances and consensus have been
      achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and
      chromophobe RCC. Nevertheless, little is known on the characteristics of several
      newly-identified RCCs, including clear cell (tubulo) papillary RCC, Xp11
      translocation RCC, t(6;11) RCC, succinate dehydrogenase (SDH)-deficient RCC,
      acquired cystic disease-associated RCC, hereditary leiomyomatosis RCC syndrome
      associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic
      RCC and hybrid oncocytic/chromophobe tumors (HOCT). In current review, we will
      collect available literature of these newly-described RCCs, analyze their
      clinical pathologic characteristics, discuss their morphologic and
      immunohistologic features, and finally summarize their molecular and genetic
      evidences. We expect this review would be beneficial for the understanding of
      RCCs, and eventually promote clinical management strategies. 

PMID- 27041928
TI  - PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer.
AB  - The incidence of prostate cancer (PCa) is rising steadily among males in many
      countries. Serum prostate-specific antigen (PSA) is widely applied to clinical
      diagnosis and screening of PCa. However, the so-called grey area of PSA levels
      4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of
      negative biopsy and overtreatment. So in order to treat PCa patients in early
      stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3
      gene, a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa)
      cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3
      has already under clinical application. PCA3 is strongly overexpressed in
      malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3
      is considered to be a promising biomarker in clinical diagnosis and targeted
      therapy. The diagnostic significance of PCA3, however, is awaiting further
      researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene
      fusion is identified as the predominant genetic change in patients diagnosed with
      PCa. Recent study revealed that combination of the PCA3 and TMPRSS2-ERG gene
      fusion test optimizes PCa detection compared with that of single biomarker, which
      would lead to a considerable reduction of the number of prostate biopsies. In
      this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion
      detection in the diagnosis of PCa. 

PMID- 27041929
TI  - The benign mimickers of prostatic acinar adenocarcinoma.
AB  - As the most frequent malignant histological subtype in prostatic cancer,
      prostatic acinar adenocarcinoma (PAA) has a series of benign mimickers including
      prostatic or non-prostatic lesions and normal structures, which may lead to an
      erroneous diagnosis and inappropriate treatment. It is very important to be aware
      of the existence of these mimickers and to recognize their histological features.
      The differential diagnosis should be based on a comprehensive evaluation of
      clinical history, histological structure, cytological morphology and the results
      of immunohistochemistry (IHC) staining, rather than on single criteria (e.g., the
      presence of prominent nucleoli or basal cell layer). 

PMID- 27041930
TI  - Epigenomics of clear cell renal cell carcinoma: mechanisms and potential use in
      molecular pathology.
AB  - Clear cell renal cell carcinoma (ccRCC) is one frequent form of urologic
      malignancy with numerous genetic and epigenetic alterations. This review
      summarizes the recent major findings of epigenetic alterations including DNA
      methylation, histone modifications, microRNAs and recently identified long
      noncoding RNAs in the development and progression of ccRCC. These epigenetic
      profilings can provide a promising means of prognostication and early diagnosis
      for patients with ccRCCs. With the developed high-throughput technologies
      nowadays, the epigenetic analyses will have possible clinical applications in the
      molecular pathology of ccRCC. 

PMID- 27041931
TI  - Understanding the molecular pathogenesis and prognostics of bladder cancer: an
      overview.
AB  - The knowledge of cellular mechanisms in malignances of the bladder has grown
      exponentially. Molecular technologies have led to the discovery of the molecular
      pathways distinguishing low-and high-grade urothelial neoplasms. This trend
      portends the future in which the classification and diagnosis of the bladder
      tumors through morphologic analysis will be supported by molecular information
      correlating with prognosis and targeted therapy. This article outlines tumor
      molecular pathology of bladder cancer with an emphasis on several promising
      candidate biomarkers that may soon make their transition to the realm of clinical
      management of bladder cancer. 

PMID- 27041932
TI  - Intraductal carcinoma of prostate (IDC-P): from obscure to significant.
AB  - The concept of intraductal carcinoma of prostate (IDC-P) has evolved over the
      years and its clinicopathologic significance has come to be more clearly
      appreciated. In contrast to morphologically malignant intraductal lesions that
      represent earlier stages of the malignant process in other anatomic sites such as
      the breast, IDC-P has now been generally recognized as a prognostically
      unfavorable manifestation of later stage spreading of its invasive counterpart.
      We here briefly review the evolution of the IDC-P concept, the histological
      diagnostic criteria and differential diagnosis, the clinical significance, as
      well as recent molecular data of IDC-P. 

PMID- 27041933
TI  - The pathology of urinary bladder lesions with an inverted growth pattern.
AB  - Inverted lesions in the urinary bladder have been the source of some difficulty
      in urological pathology. The two common ones are von Brunn's nests and cystitis
      cystic/cystitis glandularis, which are considered normal variants of urothelium.
      Apart from them, a number of other rare urothelial lesions with inverted growth
      pattern occur in the urinary bladder. Some of them are only reactive conditions,
      just as pseudocarcinomatous hyperplasia. Some are benign tumors, namely inverted
      papilloma. Whereas others are malignant neoplasms, including inverted papillary
      urothelial neoplasm of low malignant potential (PUNLMP), non-invasive inverted
      papillary urothelial carcinoma (low-grade and high-grade), and invasive
      urothelial carcinoma (inverted, nested and big nested variants). Because of the
      overlapping morphological features of all the inverted lesions mentioned above,
      even between high-grade invasive carcinoma and pseudocarcinomatous hyperplasia
      which are only a kind of reactive conditions, it is very important for the
      surgical pathologist to recognize and be familiar with these inverted lesions in
      urinary bladder. In this article, we review these spectrums of inverted lesions
      of the urinary bladder. Emphasis is placed on histogenesis, morphology,
      differential diagnosis of these lesions, and the pathologic grading of the non
      invasive inverted neoplasms, such as inverted papilloma, inverted PUNLMP, non
      invasive inverted papillary urothelial carcinoma with low-grade, and non-invasive
      inverted papillary urothelial carcinoma with high-grade. 

PMID- 27041934
TI  - Molecular aspects of prostate cancer with neuroendocrine differentiation.
AB  - Neuroendocrine differentiation (NED), which is not uncommon in prostate cancer,
      is increases in prostate cancer after androgen-deprivation therapy (ADT) and
      generally appears in castration-resistant prostate cancer (CRPC). Neuroendocrine
      cells, which are found in normal prostate tissue, are a small subset of cells and
      have unique function in regulating the growth of prostate cells. Prostate cancer
      with NED includes different types of tumor, including focal NED, pure
      neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and
      more studies are carried out on NED in prostate cancer, the molecular components
      that are involved in NED are still poorly elucidated. We review neuroendocrine
      cells in normal prostate tissue, NED in prostate cancer, terminology of NED and
      biomarkers used for detecting NED in routine pathological practice. Some recently
      reported molecular components which drive NED in prostate cancer are listed in
      the review. 

PMID- 27041935
TI  - The pathology of unusual subtypes of prostate cancer.
AB  - There are some current literatures describing the morphologic change of prostate
      carcinoma variants. Some subtypes do not respond to hormone deprivation therapy,
      for example adenosquamous and squamous cell carcinoma (SQCC), basaloid and
      adenoid cystic carcinoma (ACC), small cell carcinoma (SmCC), sarcomatoid
      carcinoma, urothelial carcinoma; some are defined in special Gleason grade, some
      develop different prognosis. So, it is very important to identify these rare
      subtypes to avoid misdiagnosis. In this review, we aim to describe the typical
      clinicopathological features of the rare variants of prostate cancer, including
      prostate acinar adenocarcinoma morphologic variants. 

PMID- 27041936
TI  - Chinese version of NCCN Clinical Practice Guidelines in Oncology officially
      authorized by NCCN.

PMID- 27041937
TI  - Iron, HCV and the liver.

PMID- 27041938
TI  - Histopathology and immunohistochemistry of large hepatocellular carcinoma with
      undetectable or low serum levels of alpha-fetoprotein.
AB  - AIM: To explore the pathomorphological characteristics of large hepatocellular
      carcinoma (LHCC) with low serum alpha-fetoprotein (AFP) level. METHODS: Specimens
      obtained from surgically resected LHCC with undetectable or low levels of serum
      AFP were fixed in formalin, embedded in paraffin, and prepared as serial
      sections. Routine hematoxylin and eosin as well as immunohistochemical stains
      (LSAB method) were used to test for expression of AFP, alpha-1-antitrypsin,
      epithelial membrane antigen, and vimentin. Some characteristics of the
      histopathological changes and immunohistochemical reactions of the cancerous
      tissues were observed under the light microscope. RESULTS: The majority of the
      cases (19/30) of LHCC with undetectable or low levels of serum AFP were of the
      clear-cell-type HCC, with 2 being positive for AFP expression at the periphery of
      the cytoplasm. CONCLUSION: The clear cell is the morphological manifestation of
      disturbance in glycogen and/or lipid metabolism of hepatoma cells. Such changes
      might be one of the factors hindering the synthesis of AFP and resulting in
      negative or low level serum AFP of the patient.

PMID- 27041939
TI  - Recovery of allografted small intestine function.
AB  - AIM: To investigate recovery of the allografted small intestine function after
      clinical small bowel transplantation (SBT). METHODS: The structure of the graft
      was evaluated by endoscopic biopsy and histopathologic examination. Graft
      functions were assessed by D-xylose absorption, barium studies, nitrogen balance
      calculation, and blood and stool cultures. Nutritional status of the recipients
      was judged by measurement of body weight and serum protein concentrations.
      RESULTS: The recipient discontinued total parenteral nutrition (TPN) and resumed
      oral nutrition 100 d after SBT. On oral diet, the patient maintained a normal
      nutritional status, gained weight by 3 kg, and had a normal serum albumin
      concentration (40.2 g/L +/- 0.2 g/L). Satisfactory D-xylose absorption was
      achieved 8 wk after the operation. Nitrogen balance of the gut was maintained
      well and increased gradually. Serial mucosal biopsy showed normal structures 2 wk
      after grafting, without evidence of rejection and graft versus host diseases
      (GVHD). Barium studies conducted on the 10(th) day and 38(th) day by barium
      studies revealed that the grafted small bowel motility showed normal patterns of
      peristalsis and transit. No bacterial translocations were noted. CONCLUSION:
      Function of the grafted small intestine recovered satisfactorily 100 d after
      transplantation, indicating good clinical outcome of SBT.

PMID- 27041940
TI  - Effects of tetrandrine and verapamil on fibroblastic growth and proliferation.
AB  - AIM: To investigate the effect of tetrandrine (Tet) and verapamil (Ver) on liver
      fibrosis by evaluating their effects on the growth and proliferation of
      fibroblasts. METHODS: Flow cytometry and imaging analysis were used to study the
      effects of combined and individual treatment of Tet and Ver on fibroblastic
      proliferation in vitro. Untreated control cells were used for comparison.
      RESULTS: Compared to untreated fibroblasts, those treated with both Tet and Ver
      showed higher percentages of cells in the G1 and G2+M phase in the cell cycle of
      3T6 fibroblasts (P < 0.01) and markedly elevated protein content, while those
      treated with Tet only showed significantly lower intracellular RNA content (1.5
      2.0 MUg, P < 0.01) and those treated with Ver only showed lower intracellular DNA
      content (15-20 MUg, P < 0.01). CONCLUSION: The inhibitory action of Tet and Ver
      on fibroblastic growth and proliferation might be responsible for the
      antifibrotic effects of these medications in liver fibrosis.

PMID- 27041941
TI  - Effect of octreotide on cell-cycle kinetics and serum carcinoembryonic antigen
      level in hepatic metastases of colonic adenocarcinoma.
AB  - AIM: To study the inhibitory effect of somatostatin analogue (octreotide) on
      tumor growth. METHODS: The influence of cell-cycle kinetics on hepatic metastases
      of BALB/c mice colonic adenocarcinoma (CT26) with octreotide treatment in vivo
      was investigated by flow cytometry. The serum carcinoembryonic antigen (CEA)
      levels were also determined. RESULTS: The results showed that the proliferative
      index (PI) and the S-phase fraction in hepatic tumors of mice treated with
      octreotide decreased markedly and that the G0/G1 serum CEA phase fraction
      increased significantly in comparison with the control (P < 0.01). After
      administration of octreotide, the serum CEA levels were also lower than those in
      the control group. The incidence of liver metastases in the treated group was
      lower than that in the control. The body weight loss in the mice was slower and
      survival was longer in the treated group than in the control group. Furthermore,
      the changes in PI and the fraction distribution of S-phase or G0/G1-phase in cell
      cycle were closely related to the serum CEA levels. CONCLUSION: Octreotide may be
      useful for inhibiting the hepatic metastases of colonic carcinoma.

PMID- 27041942
TI  - Effect of faeces trogopterorum extract B1 on the experimental gastric ulcer and
      gastric secretion in rats.
AB  - AIM: To study the effects of extracts B1, B2, and B3 from faeces trogopterorum on
      the experimental gastric ulcer in rats. METHODS: Two different animal models of
      gastric ulcers were used in this experiment: Shay's model (n = 72) and the
      reserpine-induced ulcer model (n = 76). The total volume and the pH of the
      gastric juices were recorded. The lesion scores of gastric mucosa were also
      recorded. RESULTS: The lesion scores of gastric mucosa in the Shay's model of
      animals in the WLZ-B1 groups treated with either 40 g/kg or 80 g/kg were 8.6 +/-
      10.8 and 1.6 +/- 1.9 respectively, which were lower than that of the 0.9% NaCl
      control group (47.0 +/- 31.4, P < 0.05, P < 0.01). The lesion scores for the 80
      g/kg group was lower compared to those of the Ran group (20.5 +/- 16.4, P <
      0.01). The pH of the gastric juices of the 80 g/kg group (3.425 +/- 0.143) was
      higher than that of the 0.9% NaCl group (2.836 +/- 0.632, P < 0.05). In the
      reserpine model, the lesion score of the 40 g/kg group of the WLZ-B1 (20.7 +/-
      16.5) was also lower than that of the 0.9% NaCl control group (76.3 +/- 50.6, P <
      0.05). CONCLUSION: B1 is the most effective of the three sections in inhibiting
      gastric secretion, protecting gastric mucosa and preventing experimental
      ulceration.

PMID- 27041943
TI  - Fos expression in catecholaminergic medullary neurons induced by chemical
      stimulation of stomach projecting to the paraventricular nucleus of the
      hypothalamus in rats.
AB  - AIM: To determine whether medullary catecholaminergic neurons expressing Fos
      induced by chemical stimulation of the stomach project to the paraventricular
      nucleus of hypothalamus (PVH) in rats. METHODS: Horseradish peroxidase (HRP) was
      introduced stereotaxically into the PVH of rats. Histochemical analysis of
      coronal sections through the medulla were analyzed using triple-label
      immunohistochemistry to identify cells that were retrogradely labeled with HRP,
      Fos (ABC method), and tyrosin hydroxylase (TH) (PAP method). RESULTS: Seven kinds
      of labeled neurons were found in the nucleus tractus solitarii (NTS), the
      ventrolateral medulla (VLM) and the reticular formation (RF) of the medulla: Fos
      like immunoreactive (FosLI) neurons, TH-like immunoreactive (TH-LI) neurons and
      HRP retrogradely single-labeled neurons, FosLI/HRP, FosLI/TH-LI and HRP/TH-LI
      double-labeled neurons, and FosLI/HRP/TH-LI triple-labeled neurons. CONCLUSION:
      Ascending projections from the NTS, VLM and RF to the PVH might be involved in
      the transmitting process of visceral noxious stimulation.

PMID- 27041944
TI  - Characteristics of DNA repair induced by DNA polymerase beta in hepatoma cells
      after gamma-ray irradiation.
AB  - AIM: To investigate the effects of DNA repair induced by DNA polymerase beta in
      hepatoma cells after gamma-ray irradiation. METHODS: Cell nuclei were prepared
      from mouse model (SMMC LTNM), in which human hepatoma cells are transplanted on
      nude mice. The nuclei were then irradiated with (60)Co-gamma rays at different
      dose levels or dose rates. A selective inhibitor test was then used to detect the
      effects of the radiation on DNA repair using N-ethylmaleimide (NEM) and ddTTP as
      selective inhibitors to DNA polymerases gamma and beta respectively. RESULTS:
      (3)H-TTP incorporation into irradiated nuclei or calf thymus DNA was
      significantly higher than that the rate at which it is incorporated into non
      irradiated nuclei when either DNA polymerase beta or gamma was inhibited. When
      both NEM and ddTTP are present, the (3)H-TTP incorporation in irradiated DNA was
      not significantly different from the non-irradiated nuclei. Furthermore, (3)H-TTP
      incorporation into DNA of SMMC-LTNM hepatoma nuclei was higher than that of
      normal hepatocyte nuclei (P < 0.01). This suggests that DNA repair induced by DNA
      polymerase beta was more active in hepatoma cell nuclei than in normal hepatocyte
      nuclei. CONCLUSION: DNA polymerase beta may be more responsive to DNA damage in
      some tumor cells than that in normal cells, which may facilitate the cells to
      repair DNA damages from radiation more efficiently.

PMID- 27041945
TI  - Short- and long-term effect of interferon therapy for chronic hepatitis C.
AB  - AIM: To study the short and long-term effect of interferon therapy for chronic
      hepatitis C. METHODS: Sixty-eight patients with chronic hepatitis C were treated
      with interferon (3 * 10(6) IU, im/2 d, for a course of three months) with 1 to 5
      courses of treatment and followed for 1.5 to 3 years after the therapy. RESULTS:
      According to antiviral effect of interferon, 76.5% (52/68) of the cases had a
      complete response by the end of the first therapy course, while 20.6% (14/68) and
      2.9% (2/68) had a partial response or non-response. Over a half of the patients
      with a complete response (27/52, 51.9%) relapsed within 6 to 10 mo after the
      first course. Of the original cohort, nineteen patients received two courses of
      therapy, while one patient received three and another three received five courses
      of therapy. The follow-up for these patients was between 1.5 to 3 years, at which
      time 29 (42.7%) of the patients sustained a complete response, with four of them
      having HCV RNA positive serum, while the others had either a partial (37/68,
      2.9%) or non-response. CONCLUSION: Interferon therapy had a high short-term
      complete response but a low long-term complete response in the treatment of
      chronic hepatitis C.

PMID- 27041946
TI  - Protective effect of vitamin E on age-related alterations of Kupffer cell energy
      metabolism.
AB  - AIM: To investigate the mechanism of age-related reduction of Kupffer cell (KC)
      phagocytic capacity and the protective management. METHODS: Using rhodamine 123
      fluorescence density and rate of glucose utilization as parameters, we measured
      the mitochondrial energy metabolism status in vitro and the glucose utilization
      capacity of isolated rat liver Kupffer cells (KCs) from rats of various ages (6
      mo, 12 mo, 18 mo and 24 mo) and the effect of vitamin E (VE) pretreatment (500
      mg/kg/wk * 13 wk). RESULTS: The rate of KC glucose utilization and the rhodamine
      fluorescence density of KC mitochondria of 18 mo-old untreated rats (NVEG) were
      significantly lower than that of 6 mo-old NVEG by 19.3% (4.0 nmol.h +/- 0.4
      nmol.h(-1) 10.6 cells(-1) vs 5.7 nmol.h +/- 0.6 nmol.h(-1) 10(6) cells(-1), P <
      0.05) and 19.5% (80.5 +/- 6.3 vs 100.0 +/- 4.7, P < 0.01) respectively; Rate of
      KC glucose utilization and the rhodamine fluorescence density of KC mitochondria
      of 6 mo-old rats were also lower than the 24 mo-old NVEG by 35.1% (3.7 nmol.h +/-
      0.6 nmol.h(-1)10(6) cells(-1) vs 5.7 nmol.h +/- 0.6 nmol.h(-1) 10(6) cells(-1), P
      < 0.01) and 32.1% (67.9 +/- 7.4 vs 100.0 +/- 4.7, P < 0.01) respectively. The two
      parameters of 18 mo-old VE pretreated rats (VEG) were significantly higher than
      those of 18 mo-old NVEG, and statistically comparable to those of 6 mo-old VEG.
      The two parameters of the 24 mo-old VEG were significantly higher in comparison
      with those of 24 mo-old NVEG, but still significantly lower than those of 6 mo
      old VEG. CONCLUSION: Aging has a significantly negative effect on KC energy
      metabolism, which can be alleviated by VE pretreatment.

PMID- 27041947
TI  - Alterations in p53 expression and cell proliferation in esophageal epithelia
      among patients from geographical areas with high or low incidence of esophageal
      cancer.
AB  - AIM: To study changes in p53 expression and cell proliferation in esophageal
      epithelia of subjects from high or low esophageal cancer incidence areas in Henan
      Province to understand their molecular basis. METHODS: Esophageal endoscopic
      mucosa biopsies were acquired and histopathological examinations were performed
      on 220 subjects from high esophageal cancer incidence areas and 50 subjects from
      low incidence areas in Henan Province. Esophageal epithelia were diagnosed as
      normal, basal cell hyperplasia or dysplasia based on cell morphology and tissue
      structure. Immunohistochemistry avidin biotin peroxidase complex (ABC method) was
      performed to analyze alterations in p53 and proliferating cell nuclear antigen
      (PCNA) expression in normal epithelia and epithelia with different lesion
      severities. The numbers of p53-positive and PCNA-positive cells were counted.
      RESULTS: p53- and PCNA-positive nuclei were present in esophageal epithelia from
      subjects from both high and low incidence areas. The number of PCNA-positive
      cells gradually increased with lesion severity for both the high and low
      incidence areas. The number of p53-positive cells was higher in high incidence
      areas compared to low incidence areas, and rapidly increased with lesion
      severity. p53 expression positively correlated with PCNA expression. CONCLUSION:
      The number of both p53- and PCNA-positive cells increased with lesion severity.
      p53 expression was higher in subjects from high esophageal cancer incidence areas
      compared to those from low incidence areas. These results may shed light into the
      molecular basis for the geographical distribution of esophageal cancer.

PMID- 27041948
TI  - Protective effect of rhubarb on the intestinal mucosal barrier.
AB  - AIM: To investigate the mechanism of rhubarb protection of the gut barrier.
      METHODS: The gut barrier damage models caused by hemorrhagic shock and
      intraperitoneal endotoxin were used to study the protective effect of rhubarb on
      the intestinal mucosal barrier. Rats were randomly divided into four groups, as
      follows: treatment (rhubarb) group; Positive control group; Negative control
      group; Placebo treatment group. Plasma endotoxin, tissue superoxidedismutase
      (SOD) and lipoperoxide (LPO) concentrations were measured and histological
      analysis was performed. Rhubarb was observed to have a protective effect on the
      gut. RESULTS: Rhubarb decreased intestinal permeability, attenuated endotoxin
      absorption (endotoxin serum levels: shock group 0.557 EU/mL +/- 0.069 EU/mL vs
      rhubarb group 0.345 EU/mL +/- 0.055 EU/mL), and decreased tissue SOD and tissue
      LPO levels (SOD serum, intestine and liver levels: endotoxin group 122.92 NU/mL
      +/- 43.19 NU/mL, 292.24 NU/mL +/- 88.76 NU/mL, 272.70 NU/mL +/- 85.79 NU/mL vs
      rhubarb group 312.23 NU/mL +/- 54.93 NU/mL, 391.09 NU/mg +/- 98.16 NU/mg, 542.86
      NU/mg +/- 119.93 NU/mg; LPO content in the intestine and liver: endotoxin group
      8.57 MUmol/L +/- 2.58 MUmol/L, 86.97 MUmol/L +/- 46.54 MUmol/L vs rhubarb group
      3.05 MUmol/L +/- 1.13 MUmol/L, 13.18 MUmol/L +/- 19.64 MUmol/L). Gut
      histopathology revealed that rhubarb promoted goblet cell proliferation,
      increased mucus secretion and protected intestinal mucosa in the hemorrhagic
      shock model. CONCLUSION: Rhubarb may protect the gut barrier by decreasing
      intestinal permeability, scavenging oxygen free radicals, and promoting goblet
      cell proliferation within the intestinal mucosa.

PMID- 27041949
TI  - Exploration of the immunoreactivity of the Traditional Chinese medicine
      Shenrouyangzhentang to vasoactive intestinal polypeptide.
AB  - AIM: To study the immunoreactivity of the Chinese medicine Shenrouyangzhentang to
      vasoactive intestinal polypeptide (VIP) and its therapeutic mechanism. METHODS:
      The immunoreactivity of the Chinese medicine Shenrouyangzhentang to VIP was
      detected in the plasma of 20 normal people and 20 patients with Piyinxu (Spleen
      Yin deficiency) using the radioimmunoassay (RIA) method. RESULTS: The maximum
      binding rate B0/T was 53.29%, the non-specific binding rate N0/T was 1.170%, and
      the VIP standard curve was Y = 0.81983 + 0.44319X - 0.28927X(2), R(2) = 0.990.
      The VIP content in Shenrouyangzhentang was 106.6 ng/L +/- 20 ng/L), while it was
      90.16 ng/L +/- 15 ng/L in normal human plasma and 63.25 ng/L +/- 11 ng/L in the
      plasma of Pixinxu patients. The difference between normal plasma and Pixinxu
      patient plasma was statistically significant (P < 0.05). CONCLUSION: The Chinese
      medicine Shenrouyangzhentang demonstrated VIP immunoreactivity similar to that of
      normal plasma. The (vasoactive intestinal polypeptide) VIP content in Pixinxu
      patient plasma was lower than that in healthy subjects (P < 0.05).

PMID- 27041950
TI  - Immunohistochemical study of gastrin in colorectal carcinoma tissues and adjacent
      mucosa.
AB  - AIM: To study gastrin expression in colorectal carcinoma tissues and adjacent
      mucosa and discuss the function of gastrin in colorectal carcinoma. METHODS:
      Gastrin expression in colorectal carcinoma tissues and adjacent mucosa was
      examined in 58 cases using immunohistochemical and immunoelectron microscopy.
      RESULTS: A total of 35.1% of colorectal carcinoma transitional mucosa (TM), 48.3%
      of nontypical dysplasia mucosa and 60.3% of carcinoma tissue were positive for
      gastrin expression (P < 0.05). Immunoelectron microscopy revealed that protein A
      gold (PAG) granules localized to different electron-dense secretory granules in
      carcinoma cells, the intercellular spaces, and the microvillar membrane surface.
      CONCLUSION: Gastrin expression in colorectal carcinoma tissue and adjacent
      mucosa, and the release of gastrin by carcinoma may be an initiating factor in
      carcinoma occurrence and development. Positive gastrin expression in colorectal
      carcinoma tissues can serve as a differentiation marker.

PMID- 27041951
TI  - Ultrastructural cytochemical study of enzymes expressed by signet ring cells in
      gastric cancer.
AB  - AIM: To study the ultrastructural localization of five marker enzymes (ALPase,
      ACPase, G6Pase, TPPase and CCOase) in gastric cancer signet ring cells to
      demonstrate their biologic behaviors. METHODS: Five marker enzymes were examined
      in signet ring cells of seven gastric cancer patients by ultrastructural enzyme
      cytochemical techniques. RESULTS: The number of corresponding organelles and the
      activities of marker enzymes, especially ACPase and TPPase, increased, leading to
      stronger mucus synthesis, secretion and digestion in gastric cancer signet ring
      cells. There was a lack of collagenous fibers in the stroma around the cancer
      nests. CONCLUSION: Signet ring cell carcinoma is very invasive with metastasis
      rates due to the secretion of proteolytic enzymes.

PMID- 27041952
TI  - Changes in p53 and Waf1p21 expression and cell proliferation in esophageal
      carcinogenesis.
AB  - AIM: To study the correlation between changes in p53 and Waf1p21 expression and
      cell proliferation, determined by proliferating cell nuclear antigen (PCNA), at
      different stages of human esophageal carcinogenesis. METHODS: Biopsied and
      resected esophageal tissues from a high risk population of esophageal cancer in
      northern China were used in this study. All specimens were fixed in 85% alcohol
      and processed for routine histology. The avidin biotin peroxidase complex (ABC)
      method was used to detect p53, Waf1p21 and PCNA. RESULTS: Strong nuclear staining
      of p53, Waf1p21 and PCNA was observed in normal esophageal epithelium and
      epithelia with different lesion severities. As the lesions progressed to
      dysplasia (DYS) and to esophageal squamous cell carcinoma (SCC), the Waf1p21
      immunoreactivity percentage decreased. The number of Waf1p21-positive cells
      slightly increased from normal to basal cell hyperplasia (BCH), but did not
      further increase in DYS and SCC. The total number of Waf1p21-positive cells was
      lower than the number of p53-positive cells in normal and BCH esophageal
      epithelia and much lower in DYS and SCC. Waf1p21-positive cells were located in
      the third and fourth cell layers in half of the samples examined, which was 2-4
      cell layers higher than the cells expressing PCNA and p53 in the same
      histological categories of normal, BCH and DYS. CONCLUSION: Low Waf1p21 levels at
      the DYS stage may be related to a functional loss of p53. Other mechanisms may
      also be responsible for the decreased Waf1p21 expression in DYS and SCC.

PMID- 27041953
TI  - Morphological analysis of lymph vessels and capillaries in gastric carcinoma.
AB  - AIM: To investigate the morphology of lymph vessel capillaries in both human
      gastric carcinomas and their peritumoral tissues, as well as the relation of this
      morphology to lymphatic metastasis. METHODS: The morphology and fine distribution
      of both lymph vessels and capillaries in and around the primary foci of gastric
      carcinoma were studied using the 5'Nase Alpase double staining method. The total
      amount of opened vessels and the opening rate of lymph vessels and capillaries
      were counted using a light microscope (100 * magnification), and the maximal
      luminal area, perimeter and diameter were measured using an image analysis
      technique. RESULTS: Lymph vessels and capillaries displayed strong 5'Nase
      positive staining (brown and dark brown), while blood vessels and capillaries
      revealed significant Alpase activity (blue). There were many lymph vessels,
      capillaries and solid strip-like tissues found in the gastric carcinoma samples
      analyzed. The total amount of lymphatics in the metastatic group (gastric
      carcinoma vs peritumoral tissue) and non-metastatic group was 26.9 +/- 14.2 vs
      10.4 +/- 4.0, 11.4 +/- 3.4 and 9.7 +/- 3.2, P < 0.01, respectively. Their opening
      rates were 21.2 vs 47.5 and 40.4 vs 46.0, P < 0.01, respectively. Their maximal
      luminal areas were 1502.98 +/- 1236.91 vs 5526.80 +/- 4853.42; 1918.14 +/-
      2299.24 vs 3836.16 +/- 3549.16; 5526.80 +/- 4853.42 vs 3836.16 +/- 3549.16, P <
      0.05, their perimeters were 220.33 +/- 130.25 vs 441.43 +/- 276.51; 241.79 +/-
      171.13 vs 333.80 +/- 199.66; 441.43 +/- 276.51 vs 333.80 +/- 199.60, P < 0.05,
      and their diameters were 28.80 +/- 14.98 vs 59.39 +/- 28.53; 25.37 +/- 15.79 vs
      46.22 +/- 20.85; 59.39 +/- 28.53 vs 46.22 +/- 20.85, P < 0.05, respectively. In
      summary, the lymphatics found in gastric carcinoma samples from the metastatic
      group were significantly lower than those of the other groups. CONCLUSION: There
      are newly formed lymph capillaries found in gastric carcinoma. Dilation of lymph
      capillaries may be related to edema found in peritumoral connective tissues. The
      observed lymph node metastases from gastric carcinoma occur through mature lymph
      capillaries that invade in and around primary gastric carcinoma foci.

PMID- 27041954
TI  - Pathogenetic effects of salted pork in an area of China with high-risk for
      stomach cancer.
AB  - AIM: To study the pathogenetic effects of salted pork (SP) (a special food in
      Zhuanghe City, a region of northern China that is a high-risk area for stomach
      cancer) on stomach cancer, and a provide scientific basis for the primary
      prevention of stomach cancer in this high-risk region. METHODS: This study
      consisted of three distinct parts. The first part involved a study of SP
      mutagenicity and employed both the Ames test and micronuclei assay using V79
      cells. The second part included a study of SP's effect on the gastric mucosa of
      residents in the Zhuanghe area who had consumed SP for more than ten years.
      Additionally, these studies involved an analysis of the dose effect relationship
      between SP and pathological changes in gastric mucosa, with a total of 300 cases
      analyzed. The third part of this study involved an observation of the mucosal
      lesions from experimental dogs by both gastroscopy and mucosal biopsy. Six
      healthy male dogs were selected, three were fed with SP, and the others served as
      controls. RESULTS: This study revealed that SP extract could mutate Salmonella
      typhimurium TA98 and induce an increase in both the micro nuclei rate (MNR) and
      micro nuclei cell rate (MNCR) of V79 at a dose range of 20-80 MUL/mL. There were
      significant dose-effect relations between SP and either MNR or MNCR. Pathological
      changes in the gastric mucosa of local residents who had consumed SP were
      significantly different from those of the control group. In people who had
      consumed SP for ten years, mucosal lesions were found that contained evidence of
      necrosis and erosion; In those who consumed SP for ten-20 years, both hyperplasia
      and dysplasia were seen in addition to the above lesions. In individuals who had
      consumed SP for 20-30 years, severe dysplasia and malignant changes were found.
      Furthermore, SP had damaging effect on the gastric mucosa of dogs that were fed
      SP. The mucosal lesions became more severe with increased feeding time.
      CONCLUSION: SP is a strong mutagen and long-term SP exposure may result in
      repeated gastric mucosal damage and repair, ultimately leading to severe
      dysplasia and malignancy.

PMID- 27041955
TI  - Evaluation of preoperative staging in advanced gastric cancer with MRI.
AB  - AIM: To evaluate the application of magnetic resonance imaging (MRI) to the
      preoperative staging of advanced gastric cancer. METHODS: An MRI (SE sequence)
      was preoperatively performed on 34 patients with advanced gastric cancer. The
      tumors were located at the cardia fundus in 11 patients, the corpus in 14, the
      antrum in ten and throughout the entire stomach in two. The images were analyzed
      and staged on the basis of the criteria proposed by Matsushita M. The results
      were compared with the corresponding histopathologic findings to analyze the rate
      of diagnostic accordance. RESULTS: The diagnostic rate accuracy by MRI was 77.8%
      (seven out of nince) for T2 tumors; 77.3% (17 out of 22) for T3 tumors and 100%
      (three out of three) for T4 tumors, with the overall accuracy equaling 79.4%.
      When grades T3 and T4 tumors were considered as a single group to determine the
      presence or absence of extraserosal invasion using MRI technology, the diagnostic
      accuracy was 88.3%. Statistically, MRI staging showed a significant correlation
      with the corresponding histopathologic staging using the Spearman correlation
      test (rs' = 0.743, P < 0.01). When the concordance between MRI and
      histopathologic staging results were studied according to tumor location, the
      staging accuracy was highest (90.9%) in tumors located in gastric cardia fundus.
      CONCLUSION: MR imaging is moderately valuable when staging advanced gastric
      cancer, especially for tumors located in gastric cardia fundus.

PMID- 27041956
TI  - Clinical significance of PCR in Helicobacter pylori DNA detection in human
      gastric disorders.
AB  - AIM: To investigate the clinical significance of the PCR assay in the diagnosis
      of gastric Helicobacter pylori (Hp) infection. METHODS: Hp infection in gastric
      antral biopsied specimens was identified by using the polymerase chain reaction
      (PCR) to amplify the specific Hp urease gene fragments (PCR-Hp-DNA) in 154
      patients with gastrointestinal disorders. Hp urease gene oligonucleotide primers
      specific for Hp (16s rRNA) were used. Urease test and enzyme-linked immunosorbent
      assay (ELISA) for anti Hp-IgG serum were also used as controls. RESULTS: PCR-Hp
      DNA was detected in 140 (91%) of the 154 patients, where patients 114 and 125
      were found infected with Hp by urease test and ELISA Hp IgG, respectively. There
      was a marked difference in the Hp-positive rate between the PCR-Hp-DNA and the
      urease test or ELISA-Hp-IgG (P < 0.05). The Hp infection rate increased with age,
      although a minority of infected people developed signs and symptoms of gastric
      disorders. Hp infection is closely related to adenocarcinoma in both the gastric
      antrum as well as the down body of the stomach. CONCLUSION: PCR is a sensitive
      and specific method for the detection of Hp in human gastric tissues. Detection
      of Hp DNA in vivo using this approach might improve the clinical diagnosis and
      epidemiological research related to H. pylori infection.

PMID- 27041957
TI  - Immunohistochemical detection of proliferating cell nuclear antigen in
      hepatocellular carcinoma.
AB  - AIM: To investigate the expression levels of proliferating cell nuclear antigen
      (PCNA) and its correlation with the mitotic count, histological grade, and
      metastasis of human hepatocellular carcinoma (HCC). METHODS: PCNA expression was
      detected immunohistochemically with PC10 monoclonal antibody for 80 cases of HCC.
      The PCNA labeling index (LI) was assessed by counting the positively-stained
      nuclei per 500 cells. RESULTS: PCNA LI ranged from 1.8% to 91.4% (mean = 33.9%)
      in cancerous tissues, and was significantly related to the tumor size,
      histological grade, mitotic count and the metastases found in HCC samples.
      CONCLUSION: HCC Proliferation activity, as defined by PCNA immunohistochemical
      analysis, is strongly correlated with tumor invasiveness. These findings hold
      potential prognostic value for HCC patients.

PMID- 27041958
TI  - Effect of amygdalin on proliferation of rat hepatic fat-storing cells and
      collagen production in vitro.
AB  - AIM: To study the anti-fibrotic mechanism of amygdalin, a component of Semen
      Persicae, on fat-storing cells (FSC). METHODS: Livers of normal adult rats were
      perfused with Pronas E and collagenase in situ. FSC were isolated by
      centrifugation with 11% Metrizamide. The subcultured FSC were incubated with 10(
      4)-10(-8) mol/L amygdalin for 72 h, and then FSC proliferation and collagen
      production were assayed, respectively. RESULTS: Low doses of amygdalin reduced
      incorporation of L-[(3)H]-thymidine into FSC and L-[5-(3)H]-proline into secreted
      collagenase-sensitive proteins and cell layer-associated collagenase-sensitive
      proteins. the strongest effects were seen for the 10(-8) mol/L dose of amygdalin,
      which inhibited the proliferation of FSC by 25.0%, and decreased collagen
      production in medium and cell layer by 24.2% and 26.8%, respectively. CONCLUSION:
      An anti-fibrotic mechanism of amygdalin is to inhibit the proliferation and
      collagen production of active FSC.

PMID- 27041959
TI  - Hepatic arterial infusion chemotherapy and embolization in the treatment of
      primary hepatic carcinoma.
AB  - AIM: To study the effects of hepatic arterial infusion chemotherapy (HAI) or
      embolization (HAE) in the treatment of primary hepatic carcinoma (PHC) and the
      factors influencing these effects. METHODS: A retrospective analysis of 188
      patients (166 males and 22 females) with PHC treated with HAI (n = 82) or HAE (n
      = 106) was conducted. RESULTS: In the group as a whole, the percentage of
      patients experiencing therapeutic outcomes was as follows: Symptomatic relief
      (59.6%); Tumor shrinkage (55%); A decrease in blood alpha fetoprotein (AFP)
      (37.8%) and overall survival rates at 0.5, 1.0, 2.0, and 3.0 years of 75.4%, 46%,
      23.5% and 14.7%, respectively. The mean survival time in the entire group was
      12.2 mo, and the longest survival period was 50 mo. In the HAI group the survival
      rates at 0.5, 1.0. 2.0 and 3.0 years of follow-up were 61.0%, 25.4%, 4.5% and 0%,
      respectively, with a mean survival time of 7.7 mo. In the HAE group the
      corresponding survival rates were 86.8%, 61.7%, 37.8% and 26.1%, respectively,
      with a mean survival time of 15.7 mo. Eighteen patients received secondary
      surgery. Factors that had a favorable effect on therapeutic outcomes were
      presence of no or only mild liver cirrhosis, presence of stage I or Stage II
      disease, presence of only a single tumor, a tumor size less than 10 cm in
      diameter, an absence cancerous thrombus within the portal vein or hepatic arterio
      venous fistula, and HAE treatment. CONCLUSION: This study helped identify the
      effects of HAI and HAE in patients with PHC, and identified some important
      factors which influence such treatment.

PMID- 27041960
TI  - Hepatitis C virus RNA detection in serum and peripheral blood mononuclear cells
      of patients with hepatitis C.
AB  - AIM: To investigate the existence and clinical significance of hepatitis C virus
      (HCV) RNA in the serum and peripheral blood mononuclear cells (PBMC) of patients
      with hepatitis C. METHODS: HCV RNA was detected by nested polymerase chain
      reaction (Nested PCR) in serum and in PBMC of 46 patients with acute hepatitis C
      (AHC) and in 42 patients with chronic hepatitis C (CHC). RESULTS: The positive
      rate of HCV RNA in PBMC of patients with CHC was markedly higher than that of
      patients with AHC (P < 0.01). The positive rates of HCV RNA in serum of patients
      with AHC and CHC and in PBMC of patients with CHC were significantly higher than
      those of anti-HCV positive patients with normal alanine aminotransferase (ALT)
      levels (P < 0.01). HCV RNA was negative in the serum of two patients, but could
      be detected in PBMC. In 12 patients, anti HCV was negative while HCV RNA was
      positive in serum. CONCLUSION: (1) detection of serum HCV RNA by nested PCR might
      be helpful in the early diagnosis of anti-HCV negative hepatitis C; (2) liver
      damage in patients with hepatitis C might be correlated with HCV-viremia; (3)
      infection of PBMC by HCV might play an important role in chronic liver damage in
      patients with HCV and in the chronicity of its clinical course; and (4) PBMC
      might be considered as a "reservoir" for HCV.

PMID- 27041961
TI  - Expression and analysis of McAbs antigen against human hepatocellular carcinoma.
AB  - AIM: To analyze the cause of tumor antigen heterogeneity and solve the problem of
      targeting diagnosis and therapy. METHODS: Using flow cytometry, the expression of
      McAbs antigen against human hepatocellular carcinoma (HAb18, E5, F11 and HAb27)
      was investigated. Analyses of the antigen sites were made quantitatively on the
      human hepatoma cell lines (SMMC-7721; QGY-7701; BEL-7402; HHCC and 9204). In
      particular, expression of human hepatoma, its association with antigen HAg18, and
      its relation s with cell cycle in four human hepatoma cell lines using the
      methods of indirect immunofluorescence and dual-parameter DNA dyeing were
      studied. RESULTS: The corresponding antigen of McAbs HAb18, HAb27, E5 were
      expressed on the five hepatoma cell lines and F1 was expressed only on the 7721
      and 7701 hepatoma cell lines, but their mean fluorescence intensity showed
      different values on each cell line. HAb18 and HAb27 showed a relatively high
      level of expression, while E5 and F11 showed a lower level of expression. The
      value of AI (additivity index) was 136% for HAb18 and E5, 108% for HAb18 and
      HAb27, and 118.6% for E5 and H27As AI < 30% shows that both antibodies sites are
      the same, AI > 40% shows that both anti bodies sites are different, so the HAb18,
      HAb27 or E5 McAbs were combined in pairs, showing that their antigen sites were
      different. Furthermore, HAg18 antigen was expressed very highly and the positive
      rate of HAg18 was 100% in all the four human hepatoma cell lines. The was a mean
      intensity fluorescence was 8.237 +/- 1.168 for SMMC-7721; 5.627 +/- 1.678 for QGY
      7701; 4.378 +/- 1.525 for BEL-7402 is 4.378 +/- 1.525 and 7.38 +/- 1.919 for
      HHCC. However, in the normal human liver cell (QZG), HAg18 antigen showed low
      expression (0.534 +/- 0.018) and its positive rate was only 9%. The relationship
      between human hepatoma associated antigen HAb18 and the cell cycle was expressed
      at the lowest level in G0-G1 stages, a higher level in S stage and the highest
      level in G2-M stage. CONCLUSION: Analysis of the anti-hepatoma McAbs
      corresponding to antigen may provide the basis for targeted diagnosis and
      therapy. The expression heterogeneity of human hepatoma-associated antigen HAg18
      is related to the stage of cell cycle in the same cell lines, but not related to
      the stage of cell cycle in different cell lines.

PMID- 27041962
TI  - A prospective study of vertical transmission of hepatitis C virus.
AB  - AIM: To prospectively study the mechanism of mother to infant transmission of
      hepatitis C virus (HCV). METHODS: Using a nested PCR for detection of HCV RNA and
      the second generation ELISA for detection of anti-HCV, 13 pregnant women who
      suffered from post transfusion hepatitis C (PT-HCV) and their 15 babies were
      studied to evaluate mother to infant transmission of HCV. RESULTS: The total
      infection rate of HCV was 86.7% in the babies, including one case of clinical HCV
      (7.7%), three subclinical cases of HCV (23.1%), and nine inapparent cases of HCV
      (69.2%). The positive rates of anti-HCV and HCV RNA declined with the age of the
      babies, to 7.7% for anti-HCV and 15.4% for HCV RNA at the age of three years.
      CONCLUSION: Babies born to mothers infected with HCV were vertically infected
      with HCV at a high rate, but the consequences were not serious. Four fetuses
      born, born through induced labor to mothers positive for anti-HCV and HCV, were
      all infected by HCV, suggesting that the mother to infant transmission of HCV
      mainly occurred in the uterus.

PMID- 27041963
TI  - Study on clinical pathology and immunohistochemistry of chronic erosive
      gastritis.
AB  - AIM: To study the clinical pathology of chronic erosive gastritis (CEG) and
      determine the expression of epithelial tumor markers, oncoprotein p21 and
      carcinoembryonic antigen (CEA), and G cells by immunohistochemistry. METHODS:
      Gastric mucosal biopsies from 40 CEG cases were examined. Histopathology and
      Helicobacter pylori (Hp) infection were determined by light microscopy. Thirty
      one biopsies from CEG cases were immunostained with antibodies against p21, CEA,
      proliferation cell nuclear antigen (PCNA), and gastrin using the labeled
      streptavidin-biotin (LSAB) method. RESULTS: A total of 35/40 (87.5%) CEG lesions
      showed antral location; 75% of the lesions were associated with different degrees
      of atrophic change. Twenty percent presented with mild and moderate atypia of
      mucosal epithelia and 27.5% showed intestinal metaplasia. Acute inflammatory
      changes were observed in 25% of the cases. Hp was identified in 40.0% of the
      specimens. Immunohistochemistry studies showed that 67.7% of the CEG mucosal
      epithelial samples expressed oncoprotein p21 and 29.0% expressed CEA, rates
      significantly higher than those observed in control samples from a chronic
      superficial gastritis group. However, PCNA and gastrin expression in mucosal G
      cells was not significantly different between CEG samples and samples from the
      control group (P > 0.05). CONCLUSION: CEG is a chronic gastric mucosal
      proliferative lesion that expresses higher levels of p21 and CEA than control
      samples. Our observations suggest that antral location of the lesion and Hp
      infection do not participate in the pathological process of CEG.

PMID- 27041964
TI  - Preparation and application of monoclonal antibodies against hepatitis C virus
      nonstructural proteins.
AB  - AIM: To prepare hybridoma cell lines that secrete monoclonal antibodies against
      hepatitis C virus (HCV) recombinant proteins NS3 and NS5 and to evaluate their
      use in the study of HCV NS3 and NS5 antigen distribution in human liver tissue.
      METHODS: Hybridoma cell lines were generated using spleen cells from BALB/C mice
      immunized with recombinant NS3 and NS5 proteins, following conventional
      protocols. Antibody-secreting cells were screened by solid phase ELISA and cloned
      by limited dilution. The specificity of the monoclonal antibodies was determined
      by testing hybridoma culture supernatants by Western blots of E. coli expressing
      the recombinant HCV proteins and ELISA with HCV core and hepatitis B virus (HBV)
      antigens. The monoclonal antibodies were employed in immunohistochemistry studies
      to determine the distribution of HCV NS5 and NS3 antigens in 51 paraffin embedded
      human liver tissue samples. RESULTS: Eight hybridoma cell lines secreting
      monoclonal antibodies against HCV NS3 and NS5 proteins were generated and named
      2B6, 2F3, 3D8, 3D9, 8B2, 6F11, 4C6 and 7D9. Only one of them, 2B6 (secreting
      antibodies against NS3 protein), cross-reacted with the C7 polypeptide, a
      different recombinant NS3 polypeptide. The rest of the cell lines showed no cross
      reactivity with HCV core or HBV antigens. In addition, monoclonal antibodies
      against NS3 antigens did not cross-react with NS5 antigens, and vice versa. In
      immunohistochemistry studies, these monoclonal antibodies did not detect HCV
      antigens in specimens from patients infected only with HBV (n = 20). In HCV
      infected specimens (n = 31), the rates of positive detection of NS3 and NS5
      antigens were 51.6% (16/31) and 54.9% (17/31), respectively. Six of these 31
      specimens were from patients infected only with HCV and half of them were
      positive for HCV NS3 and NS5 antigens. In specimens from patients co-infected
      with HBV and HCV (n = 25), the rates of NS3 and NS5 antigen positive detection
      were 52% (13/25) and 56% (14/25), respectively, which are similar to those
      obtained in samples from patients infected only with HCV. In specimens from
      chronic active cirrhosis patients, the rates of HCV NS3 and NS5 antigen detection
      were 70.6% (12/17) and 76.5% (13/17), respectively. CONCLUSION: We successfully
      prepared monoclonal antibodies that are specific against recombinant HCV NS3 and
      NS5 proteins and could be useful for clinical immunohistochemistry diagnosis.

PMID- 27041965
TI  - Clinical and experimental study on therapeutic effect of Weixibaonizhuanwan on
      gastric precancerous lesions.
AB  - AIM: To study the therapeutic effect of Weixibaonizhuanwan on gastric
      precancerous lesions. METHODS: Thirty-six patients with gastric precancerous
      lesions were treated with Weixibaonizhuanwan for 3 mo. Thirteen (36.1%) patients
      presented with mild atrophic gastritis, 14 (38.9%) with moderate atrophic
      gastritis, and nine (25.0%) with severe atrophic gastritis. Twenty-two (61.1%)
      and 27 (75.0%) of the cases were accompanied by intestinal metaplasia (IM) and
      dysplasia (DYS), respectively. Twenty of the 36 patients were men and 16 were
      women, ranging from 30 to 67 years in age, with 61.1% of the patients being 40-59
      years old. The duration of the disease in these patients ranged from 3 mo to 21
      years, with 20 (55.6%) patients experiencing durations of the disease between 5
      and 10 years. The clinical manifestations of the disease in these patients
      included fullness of the abdomen (31 cases), abdominalgia (27 cases), anorexia
      (30 cases), eructation (26 cases), pantothenic acid (6 cases), and loose stool (9
      cases). Patients were treated with Weixibaonizhuanwan and symptom improvement,
      level of atrophy of the gastric mucosa, and IM and DYS progression were analyzed.
      RESULTS: After a 3-mo treatment with Weixibaonizhuanwan, seven patients
      experienced recovery. The treatment was effective in 11 cases, improved symptoms
      in 13 cases, and was ineffective in five cases. The overall efficacy rate was
      86.1%. In patients with mild atrophic gastritis (n = 13), 11 improved into
      superficial gastritis and two experienced no improvement. In 14 cases of moderate
      gastritis, four cases improved into superficial gastritis and seven turned into
      mild atrophic gastritis, with three patients experiencing no improvement. Among
      severe atrophic gastritis patients (n = 9), five improved into moderate atrophic
      gastritis after treatment and four experienced no improvement. The overall
      efficacy rate in chronic atrophic gastritis patients was 77.8%. Among 9 patients
      with IM, IM disappeared in six cases, whereas three cases showed no improvement
      after treatment. In cases with moderate IM (n = 10), IM disappeared in two,
      turned into mild IM in five, and showed no change in three. Out of four cases
      with IM, one case turned into moderate IM and three showed no change. The overall
      efficacy rate in IM patients was 63.6%. Out of 16 cases of mild DYS, DYS
      disappeared in 11, whereas five cases showed no change. Out of nine cases of
      moderate DYS, DYS disappeared in two and turned into mild DYS in five cases, with
      two patients experiencing no change after treatment. No improvement was observed
      in the two cases of severe DYS after treatment. The overall efficacy rate in DYS
      patients was 66.7%. After treatment, expression of carcinoembryonic antigen (CEA)
      and proliferating cell nuclear antigen (PCNA) in gastric mucosa significantly
      decreased (P < 0.01). Before treatment, cancer staging of these patients by
      positive CEA expression was I, II, III, and IV in 13, 12, 9, and 2 cases,
      respectively. After treatment, the number of cases per stage changed to 25, 7, 3,
      and 1, respectively. Similarly, before treatment, staging by positivity of PCNA
      expression was I, II, III, and IV in 16, 11, 10, and 4 cases, respectively, and
      changed to 21, 9, 5, and 1, respectively, after treatment. CONCLUSION: The use of
      Weixibaonizhuanwan in the treatment of gastric precancerous lesions showed
      promising therapeutic effects in patients after 3-mo treatments.

PMID- 27041966
TI  - Expression of insulin-like growth factor II and its receptor in liver cells from
      patients with chronic liver diseases.
AB  - AIM: To study the relationship between insulin-like growth factor II (IGF-II),
      IGF-II receptor, and chronic liver diseases and to investigate the clinical
      mechanisms of human hepatocellular carcinoma (HCC) development. METHODS: We
      analyzed IGF-II and IGF-II receptor poly (A)+ mRNA in dysplasia liver cell (DLC;
      n = 10), liver cirrhosis (LC; n = 9), and chronic active hepatitis (CAH; n = 9)
      specimens by Northern blot using human IGF-II and IGF-II receptor DNA probes
      labeled with (32) P through nick translation. RESULTS: Expression of IGF-II in
      DLC samples (10/10, 100%) was higher than in CAH (3/9, 33%) and LC samples (3/9,
      33%) (P < 0.01). Expression of IGF-II receptor in DLC samples (7/10, 70%) was
      significantly higher than in CAH (2/9, 22%) and LC samples (3/9, 33%). Data on
      hepatitis B virus (HBV) infection status from different chronic liver disease
      samples were also analyzed. CONCLUSION: Overexpression of IGF-II and IGF-II
      receptor in DLC samples was associated with a preceding step to malignant
      phenotype hepatocyte transformation and may be of diagnostic value for early
      detection of hepatocellular carcinoma (HCC). Persistent HBV infection was
      strongly associated with abnormal IGF-II and IGF-II receptor mRNA expression,
      suggesting that an autocrine or paracrine mechanism is involved in the regulation
      of growth in liver cell carcinogenesis.

PMID- 27041967
TI  - Inflammatory bowel disease in the Hubei Province of China.
AB  - AIM: To analyze clinical features and response to treatment in inflammatory bowel
      disease (IBD) patients from the Hubei Province of China. METHODS: Clinical data
      was collected retrospectively from 74 patients with IBD [66 with ulcerative
      colitis (UC) and 8 with Crohn's disease (CD)] admitted to The Second Hospital,
      Hubei Medical University from 1986 to 1995. RESULTS: The most common symptoms in
      IBD patients were abdominal pain, diarrhea, blood and mucus in stool, and
      constipation. Extraintestinal manifestations of IBD were not common. In these
      patients, inflammation was predominantly located in the sigmoid and left colon in
      UC cases, and in the ileum and colon in CD cases. Treatment with sulphasalazine
      and corticosteroids was effective in 95% of UC cases; However, about 42% of UC
      patients showed disease recurrence during the follow-up period of 1.11 years.
      Five out of eight CD patients had part of their intestine removed, whereas three
      were treated with anti-tuberculosis drugs or the antibiotic metronidazole. Out of
      four patients we followed up for 1-8 years, one died of severe complications
      after surgery, two experienced recurrence while in treatment with drugs, and one
      remained in remission under sulphasalazine treatment after surgery. CONCLUSION:
      Five percent of the patients reported a family history of IBD. About 34% of the
      patients were smokers and 32% of the patients were alcoholic. Epidemiological
      studies are urgently needed in the Hubei Province of China to assess the role
      that genetics and environmental factors play in the pathogenesis of inflammatory
      bowel diseases.

PMID- 27041968
TI  - Preliminary study on the pathological model of Piyinxu in rats.
AB  - AIM: To study the method of constructing a pathological model of Piyinxu (spleen
      yin deficiency) using Sprague-Dawley rats and to make preliminary observations.
      METHODS: Folium sennae (0.8 g) and tabellae thyroidei (80 mg) were given daily by
      stomach feeding to each rat for 12 d to establish the pathological model of
      Piyinxu. The activity of the rats and the characteristics of their stool were
      observed. RESULTS: We observed not only the symptoms of Pixu, such as diarrhea,
      poor appetite, abdominal distention, weight loss, but also Yinxuneire (endogenous
      heat), such as increase in water drinking, nervousness, and restlessness. These
      symptoms were all different from that of the control group of Piyangxu (spleen
      yang deficiency). CONCLUSION: Combining folium sennae and tabellae thyroidei is
      an effective method for establishing a pathological model of Piyinxu.

PMID- 27041969
TI  - Relationship between loss of heterozygosity of deleted in colorectal carcinoma
      gene microsatellites and prognosis of colorectal adenocarcinoma.
AB  - AIM: To investigate the relationship between the loss of heterozygosity (LOH) of
      microsatellites on the deleted in colorectal carcinoma (DCC) gene and prognosis
      of colorectal adenocarcinoma. METHODS: A retrospective study of 58 colorectal
      adenocarcinoma cases with follow-up data and paired control normal mucosal
      tissues from 1983 to 1985 from files from the West China University of Medical
      Sciences Department of Pathology was carried out by PCR microsatellite analysis.
      Sixteen, 35, and seven cases had well-, moderately, and poorly differentiated
      tumors, respectively; 11, 30, and 17 cases were staged as Dukes' A, B, and C,
      respectively. RESULTS: LOH of DCC microsatellites was detected in 18 cases
      (31.0%). The 5-year survival rate between LOH-positive and LOH-negative patients
      was 44.4% and 77.5%, respectively (P < 0.05). The results suggest that LOH of DCC
      microsatellites correlate with prognosis but not with differentiation (P > 0.05)
      and Dukes' stage (P > 0.05) in colorectal adenocarcinoma. CONCLUSION: LOH of DCC
      microsatellites may be a marker of malignancy. Combined with the traditional
      prognostic indicators, LOH can predict prognosis of colorectal adenocarcinoma.

PMID- 27041970
TI  - Expression of the c-erbB-2 proto-oncogene product in gastric carcinoma and
      precancerous lesions.
AB  - AIM: To study the relationship between the expression of the c-erbB-2 proto
      oncogene product with gastric mucosal carcinogenesis and the behavior of gastric
      carcinoma. METHODS: Specimens from nine normal gastric mucosa, 23 gastric mucosal
      dysplasia (10 slight, six moderate, seven severe), 18 early gastric carcinoma,
      and 30 advanced gastric carcinoma were marked with P185 monoclonal antibody using
      the immunohistochemical peroxidase-avidin-biotin complex method. The relation
      between P185 expression with histological type, size, and lymph node metastasis
      of gastric carcinoma were analyzed. RESULTS: Normal gastric mucosa was negative
      for P185; Only a few cells in the neck region of the mucosal glands were very
      weakly positive. Relatively high positive rates were found in the slight,
      moderate, and severe dysplasia specimens (50%, 83.3%, and 85.7%, respectively). A
      22.2% and 56.7% P185-positive rate was found in early gastric carcinoma and in
      advanced gastric carcinoma, respectively. Statistically, the P185-positive rates
      in severe dysplasia and advanced gastric carcinoma were significantly higher than
      that in early gastric carcinoma (P < 0.05). The P185-positive rate in the group
      with lymph node metastasis was significantly higher than that of the group
      without lymph node metastasis (59.3% vs 23.8%, P < 0.05), but P185 expression was
      not related to histological type and size of gastric carcinoma. CONCLUSION: The c
      erbB-2 proto-oncogene might participate in gastric mucosal proliferation, repair,
      and carcinogenesis, and gastric carcinoma with P185 expression might have a
      stronger potential of infiltration and metastasis.

PMID- 27041971
TI  - Radiotherapy of 180 cases of operable esophageal carcinoma.
AB  - AIM: To compare the validity of radiotherapy and surgery for operable esophageal
      carcinoma in 180 patients with pathologically proven esophageal carcinoma who had
      been accepted for surgery, but for various reasons were given radical radiation
      therapy instead. METHODS: The reasons for abandoning surgery were poor cardiac
      function (n = 21), poor pulmonary function (n = 36), poor general condition (n =
      9), senility (age 69-81 years, n = 32), and refusal by the patient (n = 82). They
      were treated by the isocenter technique alone or anteroposterior plus isocenter
      irradiation at a total dose of 50-70 Gy/5-7 wk. RESULTS: The 1-, 3-, and 5-year
      survival rates were 64%, 34%, and 23%, respectively. The 3- and 5-year survival
      rates showed that lesions in the upper third esophagus responded better than
      lesions in the middle and lower third (P < 0.05). The 5-year survival rate
      following radiation alone (44.5%) of upper third lesions was slightly better than
      that following surgery. The effect on lesions following radiation to middle third
      lesions was slightly inferior to that of surgery, and that for lower third
      lesions was even poorer. CONCLUSION: The results from radiation treatment alone
      for operable esophageal carcinoma are similar to that of surgery.

PMID- 27041972
TI  - Effect of muscarinic blocker on enhancing the action of fructus aurantii
      immaturus on intestinal myoelectric activity in dogs.
AB  - AIM: To investigate the effect of fructus aurantii immaturus (FAI) on small
      intestinal electrical activity in dogs. METHODS: The effect of FAI was observed
      using a computerized electrophysiological method with the migrating myoelectric
      complex as a criterion. Fasted, healthy, and conscious dogs were given 100% FAI
      concentrated solution by gastrostogavage, and as soon as the effect on small
      intestinal electrical activity appeared, atropine was injected intramuscularly.
      RESULTS: The enhancing action of FAI was inhibited significantly by atropine, a
      cholinergic receptor antagonist. Both the number of spike bursts per cluster and
      the number of spikes per minute in phase II and III and the general cycle were
      decreased (P < 0.01), although the duration of phase II and the general cycle was
      prolonged. CONCLUSION: The effect of FAI might be related to the muscarinic
      receptors.

PMID- 27041973
TI  - Effect of remedies for enhancing resistance and relieving blood stasis on
      metastasis in postoperative gastric cancer and ornithine decarboxylase levels.
AB  - AIM: To study the action of remedies for enhancing resistance and relieving blood
      stasis on metastasis in postoperative gastric cancer and its influence on
      ornithine decarboxylase (ODC). METHODS: Sixty-three postoperative patients with
      gastric cancer were randomly divided into two groups. Thirty-one patients were
      treated with western medicine consisting of the FAP (5-fluorouracil, adriamycin,
      cisplatin) and CODP regimens (cyclophosphamide, vincristine, daunorubicin,
      prednisone), whereas 32 patients were treated with the FAP regimen and
      traditional Chinese medicine. Correlations were made between the ODC levels
      detected before and after treatment and other factors such as tumor diameter,
      infiltration depth, histological type, and lymph node metastasis. RESULTS: The
      ODC levels in the gastric cancer tissue and adjacent normal gastric mucosal
      tissue were significantly higher in the patients than in the controls. There was
      an obvious correlation between increased ODC and tumor size, infiltration depth,
      degree of differentiation, and lymph node metastasis. Six months later, there
      were no significant changes in the ODC levels of the group using only Western
      medicine, while the ODC levels decreased markedly in the group using combined
      Western and traditional Chinese medicine (P < 0.01). CONCLUSION: The effects of
      traditional Chinese medicine remedies on metastases in postoperative gastric
      cancer are related to the reduction of ODC activity.

PMID- 27041974
TI  - RACOG and wRACOG: Two Probabilistic Oversampling Techniques.
AB  - As machine learning techniques mature and are used to tackle complex scientific
      problems, challenges arise such as the imbalanced class distribution problem,
      where one of the target class labels is under-represented in comparison with
      other classes. Existing oversampling approaches for addressing this problem
      typically do not consider the probability distribution of the minority class
      while synthetically generating new samples. As a result, the minority class is
      not well represented which leads to high misclassification error. We introduce
      two Gibbs sampling-based oversampling approaches, namely RACOG and wRACOG, to
      synthetically generating and strategically selecting new minority class samples.
      The Gibbs sampler uses the joint probability distribution of attributes of the
      data to generate new minority class samples in the form of Markov chain. While
      RACOG selects samples from the Markov chain based on a predefined lag, wRACOG
      selects those samples that have the highest probability of being misclassified by
      the existing learning model. We validate our approach using five UCI datasets
      that were carefully modified to exhibit class imbalance and one new application
      domain dataset with inherent extreme class imbalance. In addition, we compare the
      classification performance of the proposed methods with three other existing
      resampling techniques.

PMID- 27041975
TI  - Perioperative Laboratory Abnormalities in Gynecologic Oncology Surgical Patients.
AB  - Background: Laboratory blood testing incurs financial costs and the blood draws
      can increase discomfort, yet minimal data exists regarding routine testing in
      gynecologic oncology surgical patients. Additionally, an increasing number of
      gynecologic oncology surgeries are performed via a laparoscopic approach. Thus,
      further investigation into perioperative laboratory testing for gynecologic
      oncology patients is warranted. An increasing number of gynecologic oncology
      surgeries are performed via a laparoscopic approach. Thus, further investigation
      into perioperative laboratory testing for gynecologic oncology patients is
      warranted. Objective: The aims of this study were (1) to evaluate the frequency
      and etiology of perioperative laboratory test abnormalities in patients
      undergoing laparoscopic and laparotomy surgery in a gynecologic oncology service,
      and (2) to establish an evidence-based algorithm to reduce unnecessary laboratory
      testing. Materials and Methods: A single-institution retrospective study was
      completed, investigating laparoscopic and laparotomic surgeries over 4 years.
      Information on preoperative and postoperative laboratory data, surgical
      parameters, perioperative interventions, and patient demographics was collected.
      Quality-assurance data were reviewed. Data were tabulated and analyzed using
      Statistical Product and Service Solutions (SPSS) version 22. A Student's t-test
      was used to test for group differences for continuous variables with equal
      variance, the Mann-Whitney-U test for continuous variables when unequal variance
      was detected, and Pearson's chi2 was used to investigate categorical variables of
      interest. p-Values <0.05 were considered to be statistically significant.
      Logistic regression was performed to investigate the relationships among multiple
      predictors and each identified outcome. Results: The study included 481 subjects
      (168 laparoscopies, 313 laparotomies). Patients undergoing laparoscopy were, on
      average, younger (53.5 versus 57.4), with lower body mass indexes (29.7 versus
      33.0) and lower rates of diabetes (10.7% versus 19.5%), compared to patients
      undergoing laparotomy. Overall, >98% of patients underwent at least one
      preoperative and postoperative laboratory test, totaling 8060 preoperative and
      5784 postoperative results. The laparoscopy group was significantly less likely
      to have postoperative metabolic abnormalities or to undergo perioperative blood
      transfusion. Patients taking an angiotensin-converting-enzyme inhibitor,
      angiotensin-II-receptor blocker, or diuretic were significantly more likely to
      have elevated creatinine preoperatively (odds ratio [OR]: 5.0; p < 0.001) and
      postoperatively (OR: 7.1; p < 0.001), and this remained true for each group when
      divided by surgical approach. Perioperative complications meeting institutional
      quality assurance criteria occurred in 1.7% of laparoscopy patients compared to
      11.8% of laparotomy patients (p < 0.001); perioperative laboratory testing was
      not a factor in the diagnosis of these complications. Conclusions: Clinically
      significant laboratory abnormalities are uncommon and are less likely to be found
      on routine perioperative testing in gynecologic oncology patients undergoing
      laparoscopy, compared to patients undergoing laparotomy. This suggests a role for
      limiting perioperative laboratory blood testing. (J GYNECOL SURG 32:111).

PMID- 27041976
TI  - An Inventory of Publicly Funded Participant-Directed Long-Term Services and
      Supports Programs in the United States.
AB  - After a decade of changes in federal law, regulation, and policy designed to
      promote the growth of publicly funded participant-directed long-term services and
      supports (PD-LTSS) programs, the number of these programs has grown considerably.
      The National Resource Center for Participant-Directed Services (NRCPDS) at Boston
      College started developing an inventory of these programs in 2010-2011 to
      determine the number and characteristics of publicly funded PD- LTSS programs in
      the United States. The 2010-2011 NRCPDS inventory provides baseline data for
      future research efforts in gauging the growth and expansion of this service
      delivery model. This article details the process for developing this data
      resource, some of the major characteristics of PD-LTSS programs in the United
      States, and discusses possible implications and areas for future research.

PMID- 27041977
TI  - Youth Negative Affect Attenuates Associations between Compromise and Mother
      Adolescent Conflict Outcomes.

PMID- 27041978
TI  - Familial Risk for Exceptional Longevity.
AB  - One of the most glaring deficiencies in the current assessment of mortality risk
      is the lack of information concerning the impact of familial longevity. In this
      work, we update estimates of sibling relative risk of living to extreme ages
      using data from more than 1,700 sibships, and we begin to examine the trend for
      heritability for different birth-year cohorts. We also build a network model that
      can be used to compute the increased chance for exceptional longevity of a
      subject, conditional on his family history of longevity. The network includes
      familial longevity from three generations and can be used to understand the
      effects of paternal and maternal longevity on an individual's chance to live to
      an extreme age.

PMID- 27041979
TI  - Biorheological Model on Flow of Herschel-Bulkley Fluid through a Tapered Arterial
      Stenosis with Dilatation.
AB  - An analysis of blood flow through a tapered artery with stenosis and dilatation
      has been carried out where the blood is treated as incompressible Herschel
      Bulkley fluid. A comparison between numerical values and analytical values of
      pressure gradient at the midpoint of stenotic region shows that the analytical
      expression for pressure gradient works well for the values of yield stress till
      2.4. The wall shear stress and flow resistance increase significantly with axial
      distance and the increase is more in the case of converging tapered artery. A
      comparison study of velocity profiles, wall shear stress, and flow resistance for
      Newtonian, power law, Bingham-plastic, and Herschel-Bulkley fluids shows that the
      variation is greater for Herschel-Bulkley fluid than the other fluids. The
      obtained velocity profiles have been compared with the experimental data and it
      is observed that blood behaves like a Herschel-Bulkley fluid rather than power
      law, Bingham, and Newtonian fluids. It is observed that, in the case of a tapered
      stenosed tube, the streamline pattern follows a convex pattern when we move from
      r/R = 0 to r/R = 1 and it follows a concave pattern when we move from r/R = 0 to
      r/R = -1. Further, it is of opposite behaviour in the case of a tapered
      dilatation tube which forms new information that is, for the first time, added to
      the literature. 

PMID- 27041980
TI  - Flow Characteristics of Distinctly Viscous Multilayered Intestinal Fluid Motion.
AB  - The goal of this investigation is to study the three layered (core layer,
      intermediate layer, and peripheral layer) tubular flow of power law fluids with
      variable viscosity by peristalsis in order to investigate the strength of the
      role played by an artificially generated intermediate layer to ease constipation.
      The solution is carried out under the long wavelength and low Reynolds number
      approximations in the wave frame of reference as the flow is creeping one. The
      stream functions for each layer such as core layer, intermediate layer, and
      peripheral layer are determined. The expressions for axial pressure gradient,
      interfaces, trapping, and reflux limits are obtained. The effects of power law
      index and viscosities on pressure across one wavelength, mechanical efficiency,
      and trapping are discussed numerically. It is found that the pressure required to
      restrain flow rates and the mechanical efficiency increase with the viscosities
      of the intermediate and peripheral layers as well as with the flow behaviour
      index. It is observed that the axisymmetric flow in intestines is less prone to
      constipation than two-dimensional flow and may be more easily overcome with
      introducing a viscous intermediate layer. 

PMID- 27041981
TI  - Assessment of Patellar Tendon Reflex Responses Using Second-Order System
      Characteristics.
AB  - Deep tendon reflex tests, such as the patellar tendon reflex (PTR), are widely
      accepted as simple examinations for detecting neurological disorders. Despite
      common acceptance, the grading scales remain subjective, creating an opportunity
      for quantitative measures to improve the reliability and efficacy of these tests.
      Previous studies have demonstrated the usefulness of quantified measurement
      variables; however, little work has been done to correlate experimental data with
      theoretical models using entire PTR responses. In the present study, it is
      hypothesized that PTR responses may be described by the exponential decay rate
      and damped natural frequency of a theoretical second-order system. Kinematic data
      was recorded from both knees of 45 subjects using a motion capture system and
      correlation analysis found that the mean R (2) value was 0.99. Exponential decay
      rate and damped natural frequency ranges determined from the sample population
      were -5.61 to -1.42 and 11.73 rad/s to 14.96 rad/s, respectively. This study
      confirmed that PTR responses strongly correlate to a second-order system and that
      exponential decay rate and undamped natural frequency are novel measurement
      variables to accurately measure PTR responses. Therefore, further investigation
      of these measurement variables and their usefulness in grading PTR responses is
      warranted. 

PMID- 27041982
TI  - Measurement of central corneal thickness by ultrasonic pachymeter and oculus
      pentacam in patients with well-controlled glaucoma: hospital-based comparative
      study.
AB  - BACKGROUND: The measurement of central corneal thickness (CCT) plays an important
      role in the diagnosis and treatment of glaucoma and many corneal diseases.
      OBJECTIVE OF THE STUDY: To compare the measurement of CCT by ultrasonic
      pachymeter with that measured by oculus pentacam in both normal subjects and
      patients with well-controlled glaucoma. PATIENTS AND METHODS: In 173 eyes of both
      controls and patients with open-angle glaucoma (normal intraocular pressure)
      attending Ibn Al Haitham Teaching Eye Hospital, CCT was measured by oculus
      pentacam and then by ultrasound pachymeter at the same morning by the same
      technicians. RESULTS: The results showed no significant difference in CCT
      readings measured by the two devices in both glaucoma and control groups
      (glaucoma group: 547.29+/-49.32 um with pentacam vs 547.66+/-45.24 um with
      ultrasound pachymeter; control group: 551.02+/-36.28 um with pentacam vs 541.25+/
      34.96 um with ultrasound pachymeter). P-values were >0.05 in both groups
      (statistically not significant). CONCLUSION AND RECOMMENDATION: Ultrasonic
      pachymeter and oculus pentacam can be used interchangeably in measuring CCT, and
      we recommend a nontouch method (in this study, pentacam Scheimpflug camera) for
      measuring CCT during assessment of patients with glaucoma or any ocular disease
      or surgery.

PMID- 27041983
TI  - Retreatments after multifocal intraocular lens implantation: an analysis.
AB  - PURPOSE: To determine the incidence and etiology of required retreatment after
      multifocal intraocular lens (IOL) implantation and to evaluate the methods and
      clinical outcomes of retreatment. PATIENTS AND METHODS: A retrospective chart
      review of 416 eyes of 209 patients from one site that underwent uncomplicated
      cataract surgery with multifocal IOL implantation. Biometry, the IOL, and
      refractive data were recorded after the original implantation, with the same data
      recorded after retreatment. Comments related to vision were obtained both before
      and after retreatment for retreated patients. RESULTS: The multifocal retreatment
      rate was 10.8% (45/416 eyes). The eyes that required retreatment had
      significantly higher residual refractive astigmatism compared with those who did
      not require retreatment (1.21+/-0.51 D vs 0.51+/-0.39 D, P<0.01). The retreatment
      rate for the two most commonly implanted primary IOLs, blended bifocal (10.5%,
      16/152) and bilateral trifocal (6.9%, 14/202) IOLs, was not statistically
      significantly different (P=0.12). In those requiring retreatment, refractive
      related complaints were most common. Retreatment with refractive corneal surgery,
      in 11% of the eyes, and piggyback IOLs, in 89% of the eyes, was similarly
      successful, improving patient complaints 78% of the time. CONCLUSION: Complaints
      related to ametropia were the main reasons for retreatment. Residual astigmatism
      appears to be an important determinant of retreatment rate after multifocal IOL
      implantation. Retreatment can improve symptoms for a high percentage of patients;
      a piggyback IOL is a viable retreatment option.

PMID- 27041984
TI  - Effect of preservative removal from fixed-combination bimatoprost/timolol on
      intraocular pressure lowering: a potential timolol dose-response phenomenon.
AB  - PURPOSE: Many patients with glaucoma require combination therapies to achieve
      target intraocular pressure (IOP) and preserve visual function. Ocular
      hypotensives often contain a preservative (eg, benzalkonium chloride [BAK]), but
      preservative-free (PF) formulations have been developed for patients with
      sensitivity. A Phase III study found the efficacy of bimatoprost 0.03%/timolol
      0.5% (bim/tim, Ganfort((r))) PF to be equivalent to that of preserved bim/tim,
      although a trend favoring bim/tim PF was observed. As BAK is a corneal
      penetration enhancer, this literature review aims to explain these findings by
      exploring the relationship between timolol concentration and its IOP-lowering
      effect. METHODS: Systematic searches were performed in Scopus and PubMed for
      clinical trials published in English between 1960 and July 2014 using the
      keywords "timolol", "intraocular pressure", and the concentrations "1%, 0.5%, OR
      0.25%". Articles that directly compared IOP-lowering effects of >=2
      concentrations of timolol were identified by manual screening, and cross-checked
      for duplication. RESULTS: Seventeen studies that included 10-371 patients were
      evaluated; the majority were randomized (16/17), double-masked (14/17), and
      enrolled patients with open-angle glaucoma or ocular hypertension (12/17). All
      studies investigated timolol in preserved formulations. Timolol concentrations
      tested ranged from 0.008% to 1.5%. Of 13 studies comparing timolol 0.25% versus
      0.5%, two found the 0.25% dose to have greater IOP-lowering effects, and three
      reported the opposite; eight reported similar IOP lowering. Results also indicate
      that timolol 0.5% may be more effective than higher concentrations. CONCLUSION:
      The evidence suggests that timolol may have an inverted U-shaped dose-response
      curve, and that its optimal IOP-lowering concentration is between 0.25% and 0.5%.
      Compared with bim/tim, removal of the permeability enhancer BAK in bim/tim PF
      could have resulted in a lower timolol concentration at the target site, bringing
      the effective concentration within the 0.25%-0.5% range and enhancing the
      efficacy of bim/tim PF.

PMID- 27041985
TI  - Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for
      age-related macular degeneration patients with large lesions.
AB  - BACKGROUND: To evaluate the effect of photodynamic therapy (PDT) using a modified
      procedure on exudative age-related macular degeneration having been
      conventionally difficult to treat. METHODS: The medical records of eight
      consecutive patients (eight eyes) with age-related macular degeneration treated
      with modified PDT were reviewed retrospectively. Modified PDT was used for the
      lesions that could not be covered by conventional use of PDT, either because the
      lesion was too large or too close to the optic disc. A moving PDT laser spot at
      constant speed, for 83 seconds, was used to cover the entire lesion, and was
      named "Ironing PDT." This retrospective study was performed with informed patient
      consent. It was approved by the Institutional Review Board of Kansai Medical
      University. RESULTS: No exudation could be found 36 months after treatment in
      five eyes (62.5%). There was no significant difference between the best-corrected
      visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR
      best-corrected visual acuity was improved in one eye, maintained in five eyes,
      and deteriorated in two eyes. CONCLUSION: Ironing PDT decreased subfoveal fluid
      and preserved visual acuity in some patients with age-related macular
      degeneration difficult to treat with conventional therapy.

PMID- 27041986
TI  - Boston type 1 keratoprosthesis from patient selection through postoperative
      management: a review for the keratoprosthetic surgeon.
AB  - For the anterior segment surgeon, the implantation of Boston type 1
      keratoprosthesis is a multistep process that begins with careful patient
      selection. Success depends on thorough preoperative evaluation, detailed surgical
      planning, and frequent postoperative follow-up. New practice patterns have
      emerged for each of these phases as the international experience with
      keratoprosthesis grows. This review details special considerations that can
      improve outcomes and also allow surgeons to consider its use in challenging
      patient populations at each step. 

PMID- 27041987
TI  - Benefits of switching from latanoprost to preservative-free tafluprost eye drops:
      a meta-analysis of two Phase IIIb clinical trials.
AB  - INTRODUCTION: Glaucoma patients frequently exhibit ocular surface side effects
      during treatment with prostaglandin eye drops. The present work investigated
      whether glaucoma patients suffering from signs and symptoms of ocular surface
      disease while using preserved latanoprost eye drops benefited from switching to
      preservative-free tafluprost eye drops. PATIENTS AND METHODS: The analysis was
      based on 339 glaucoma patients enrolled in two Phase IIIb trials. The patients
      were required to have two symptoms, or one sign and one symptom of ocular surface
      disease at baseline, and at least 6 months preceding treatment with latanoprost
      eye drops preserved with benzalkonium chloride. All eligible patients were
      switched from latanoprost to preservative-free tafluprost for a total of 12
      weeks. Ocular symptoms and ocular signs were evaluated at baseline and at 2
      weeks, 6 weeks, and 12 weeks after commencing treatment with tafluprost.
      Intraocular pressure (IOP), drop discomfort, and treatment preference were
      evaluated to investigate the clinical efficacy and patient-related outcomes.
      RESULTS: After 12 weeks of treatment with preservative-free tafluprost, the
      incidences of irritation/burning/stinging, foreign body sensation, tearing,
      itching, and dry eye sensation had diminished to one-third of those reported for
      preserved latanoprost at baseline. The incidences of blepharitis and
      corneal/conjunctival fluorescein staining had in turn decreased to one-half of
      those reported for preserved latanoprost. Severity of conjunctival hyperemia was
      halved during treatment with preservative-free tafluprost, and there was
      significant improvement in tear break-up time and tear production. A further
      reduction in IOP (~1 mmHg) was seen with preservative-free tafluprost compared
      with preserved latanoprost. Drop discomfort was alleviated during preservative
      free tafluprost treatment, and an outstanding majority of patients (72%)
      preferred preservative-free tafluprost over preserved latanoprost. CONCLUSION:
      This meta-analysis confirmed that IOP remained at the same level after replacing
      benzalkonium chloride-preserved latanoprost eye drops with preservative-free
      tafluprost eye drops. Preservative-free tafluprost significantly decreased the
      symptoms and signs of ocular surface disease and outrated latanoprost in drop
      comfort and treatment preference.

PMID- 27041988
TI  - Tamponade in the surgical management of retinal detachment.
AB  - Despite treatment advances, rhegmatogenous retinal detachment (RD) can have poor
      visual outcomes even with prompt and appropriate therapy. Pars plana vitrectomy
      is a leading management modality for the treatment of RD. This procedure is
      generally accompanied by the use of internal tamponade. Various gases and
      silicone oils may yield beneficial outcomes. Heavy silicone oils have been
      approved in some European nations but are not available in the USA. Different
      tamponade agents have unique benefits and risks, and choice of the agent should
      be individualized according to the characteristics of the patient and RD, as well
      as perioperative and postoperative factors. 

PMID- 27041989
TI  - Treatment costs of cystoid macular edema among patients following cataract
      surgery.
AB  - PURPOSE: The current costs of treating cystoid macular edema (CME), a
      complication that can follow cataract surgery, are largely unknown. This analysis
      estimates the treatment costs for CME based on the recently released US Medicare
      data. SETTING: Nationally representative database. DESIGN: Retrospective analysis
      of the 2011 through 2013 Medicare 5% Beneficiary Encrypted Files. METHODS:
      Beneficiaries who underwent cataract surgery were identified and stratified by
      diagnosis of CME (cases) or no diagnosis of CME (controls) within 6 months
      following surgery. Claims and reimbursements for ophthalmic care were identified.
      Subgroup analyses explored the rates of CME in beneficiaries based on the
      presence of selected comorbidities and by the type of procedure (standard vs
      complex). Total Medicare and ophthalmic costs for cases and controls are
      presented. The analysis explored the effect of considering diabetic macular edema
      (DME) and macular edema (ME) as exclusion criteria. RESULTS: Of 78,949
      beneficiaries with cataract surgery, 2.54% (n=2,003) were diagnosed with CME. One
      third of beneficiaries had one or more conditions affecting retinal health
      (including diabetes), 4.5% of whom developed CME. The rate of CME, at 22.5%, was
      much higher for those patients with preoperative DME or ME. Ophthalmic charges
      were almost twice as high for cases compared with controls (US$10,410 vs $5,950);
      payments averaged 85% higher ($2,720 vs $1,470) (both P<0.0001). CONCLUSION:
      Substantial costs can be associated with CME; beneficiaries whose retinas are
      already compromised before cataract surgery face higher risk. Cost savings could
      be realized with the use of therapies that reduce the risk of developing CME.
      Future analyses could identify whether and to what extent comorbidities influence
      costs.

PMID- 27041990
TI  - Macular thickness and macular volume measurements using spectral domain optical
      coherence tomography in normal Nepalese eyes.
AB  - PURPOSE: To record the normative values for macular thickness and macular volume
      in normal Nepalese eyes. METHODS: In all, 126 eyes of 63 emmetropic subjects
      (mean age: 21.17+/-6.76 years; range: 10-37 years) were assessed for macular
      thickness and macular volume, using spectral domain-optical coherence tomography
      over 6*6 mm(2) in the posterior pole. A fast macular thickness protocol was
      employed. Statistics such as the mean, median, standard deviation, percentiles,
      and range were used, while a P-value was set at 0.05 to test significance.
      RESULTS: Average macular thickness and total macular volume were larger in males
      compared to females. With each year of increasing age, these variables decreased
      by 0.556 MUm and 0.0156 mm(3) for average macular thickness and total macular
      volume, respectively. The macular thickness was greatest in the inner superior
      section and lowest at the center of the fovea. The volume was greatest in the
      outer nasal section and thinnest in the fovea. The central subfield thickness (r=
      0.243, P=0.055) and foveal volume (r=0.216, P=0.09) did not correlate with age.
      CONCLUSION: Males and females differ significantly with regard to macular
      thickness and macular volume measurements. Reports by other studies that the
      increase in axial length reduced thickness and volume, were negated by this study
      which found a positive correlation among axial length, thickness, and volume.

PMID- 27041991
TI  - Combined femtosecond laser-assisted intracorneal ring segment implantation and
      corneal collagen cross-linking for correction of keratoconus.
AB  - PURPOSE: To assess the safety, predictability, and effectiveness of Keraring
      intrastromal corneal ring segments (ICRS) insertion assisted by femtosecond laser
      and corneal collagen cross-linking (CXL) for keratoconus correction. PATIENTS AND
      METHODS: In this prospective, noncomparative, and interventional case series, 160
      eyes of 100 adult keratoconus patients with poor best-corrected visual acuity
      (BCVA) (less than 0.7) and intolerance to contact lens wear were included.
      Patients underwent femtosecond laser-assisted placement of ICRS and CXL. All
      patients were examined for a complete ophthalmological test: uncorrected visual
      acuity (UCVA), BCVA, spherical equivalent, keratometry (K1-flat and K2-steep),
      pachymetry, and Scheimpflug imaging with the Pentacam at 1 week and at 1, 3, and
      6 months postoperatively. RESULTS: At 6 months, a significant difference was
      observed (P<0.001) in mean UCVA and BCVA from 0.92+/-0.677 and 0.42+/-0.600
      logMAR preoperatively to 0.20+/-0.568 and 0.119+/-0.619 logMAR, respectively.
      Mean spherical equivalent refractions were significantly lower (P<0.001) at 6
      months. Mean keratometry (K) also significantly reduced (P<0.001) from 50.93+/
      5.53 D (K1-flat) and 55.37+/-5.76 D (K2-steep) to 47.32+/-4.61 and 51.08+/-5.38
      D, respectively. In terms of pachymetry, no significant difference was observed
      preoperatively versus postoperatively (P=1.000). CONCLUSION: Keraring ICRS
      insertion assisted by femtosecond laser and corneal CXL provided significant
      improvement in visual acuity, spherical equivalent, and keratometry, which
      suggests that it may be effective, safe, and predictable for keratoconus
      correction.

PMID- 27041992
TI  - Correlations between immunogenicity, drug levels, and disease activity in an
      Italian cohort of rheumatoid arthritis patients treated with tocilizumab.
AB  - The aim of this study was to evaluate the real-life immunogenicity of anti-drug
      antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid
      arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated
      patients with rheumatoid arthritis (16 males and 110 females; mean age 59+/-12
      years, range 26-83; mean disease duration 11+/-5 years) with inadequate 12-week
      response to any synthetic and biological disease-modifying anti-rheumatic drugs,
      in a retrospective analysis. One-hundred and seven patients were treated with
      methotrexate mean dose 12.6+/-1.3 mg/week in combination with TCZ, 13 received
      TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients
      were treated with prednisone mean dose 6.4+/-1.2 mg/day. They had a 28-joint
      Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR)
      of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after
      6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti
      citrullinated peptide antibody; ESR; CRP; TNF-alpha; and IL-6. TCZ and anti-TCZ
      antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of <10 ug/mL were
      considered low and >10 ug/mL high. After 6 months of treatment only one patient
      was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR,
      and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ
      levels of <10 ug/mL and the 42 with TCZ levels of >10 ug/mL showed the following
      differences: DAS28: 3.09+/-1.32 vs 2.78+/-1.32, P=0.0005; ESR: 27+/-14.8 vs 14+/
      12 mm/hour, P=0.0001; CRP: 1.47+/-1.05 vs 0.65+/-0.80 mg/dL, P=0.0086; TNF-alpha:
      10.2+/-1.2 vs 9.9+/-1.1 pg/mL, P=0.999; IL-6: 3.65+/-4.75 vs 3.62+/-4.41 pg/mL,
      P=0.97; anti-citrullinated peptide antibody: 85.2+/-93.7 vs 86.7+/-90.3 IU/mL,
      P=0.94; RF IgM: 72.4+/-62.7 vs 68.3+/-61.6 IU/mL, P=0.754; RF IgA: 41.7+/-36.4 vs
      47.8+/-42.1 U/mL, P=0.449; and RF IgG: 46.4+/-46.1 vs 59.3+/-58.2 U/mL, P=0.212.
      These findings show that the occurrence of anti-drug antibodies against TCZ is
      very rare and that there are statistically significant correlations between TCZ
      levels of >10 ug/mL and ESR, CRP levels, and DAS28. 

PMID- 27041993
TI  - Therapeutic effects of tyroservatide on metastasis of lung cancer and its
      mechanism affecting integrin-focal adhesion kinase signal transduction.
AB  - Tyroservatide (YSV) can inhibit the growth and metastasis of mouse lung cancer
      significantly. This study investigated the therapeutic effects of tripeptide YSV
      on metastasis of human lung cancer cells and explored its possible mechanism that
      affects integrin-focal adhesion kinase (FAK) signal transduction in tumor cells.
      YSV significantly inhibited the adhesion and the invasion of highly metastatic
      human lung cancer cell lines 95D, A549, and NCI-H1299. In addition, YSV
      significantly inhibited phosphorylation of FAK Tyr397 and FAK Tyr576/577 in the
      95D, A549, and NCI-H1299 human lung cancer cells in vitro. And the mRNA level and
      protein expression of FAK in these human lung cancer cells decreased at the same
      time. YSV also significantly inhibited mRNA and protein levels of integrin beta1
      and integrin beta3 in the 95D, A549, and NCI-H1299 human lung cancer cells. Our
      research showed that YSV inhibited adhesion and invasion of human lung cancer
      cells and exhibited therapeutic effects on metastasis of lung cancer. 

PMID- 27041994
TI  - Cost-effectiveness comparison of lamivudine plus adefovir combination treatment
      and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.
AB  - BACKGROUND/AIM: Lamivudine (LAM) plus adefovir (ADV) combination therapy is
      clinically efficacious for treating chronic hepatitis B (CHB) patients in China,
      but no pharmacoeconomic evaluations of this strategy are available. The aim of
      this study was to examine the cost-effectiveness of LAM plus ADV combination
      treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV,
      telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). METHODS: To simulate
      the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs)
      for different therapy options, a Markov model that included five initial
      monotherapies and LAM plus ADV combination as an initial treatment was developed.
      Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV;
      alternative: direct use of ETV + ADV) were considered separately for treating
      patients refractory to initial therapy. One-way and probabilistic sensitivity
      analyses were used to explore model uncertainties. RESULTS: In base-case
      analysis, ETV had the lowest lifetime cost and served as the reference therapy.
      Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy,
      and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was
      more efficacious than ETV, but also more expensive. Although the incremental cost
      effectiveness ratios of combination therapy or TDF were both higher than the
      willingness-to-pay threshold of $20,466/QALY gained for the reference treatment,
      in an alternative scenario analysis LAM plus ADV combination therapy would be the
      preferable treatment option. CONCLUSION: ETV and LAM plus ADV combination therapy
      are both cost-effective strategies for treating Chinese CHB patients.

PMID- 27041995
TI  - Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery,
      cellular uptake, and pulmonary pharmacokinetics.
AB  - Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive
      pharmacological effects, but its water solubility and oral bioavailability are
      only~46+/-6 ug/mL and 5.8%, respectively. The purpose of this study is to design
      and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged
      and sustained drug release, with improved stability, involving nontoxic
      nanocarriers, and increase the bioavailability by means of pulmonary
      administration. Initially, a group contribution method was used to screen the
      best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an
      emulsification and low-temperature solidification method and optimized using an
      orthogonal experiment approach. The morphology was examined by transmission
      electron microscopy, and the particle size and zeta potential were determined by
      photon correlation spectroscopy. The total drug content of NRG-SLNs was measured
      by high-performance liquid chromatography, and the encapsulation efficiency (EE)
      was determined by Sephadex gel-50 chromatography and high-performance liquid
      chromatography. The in vitro NRG release studies were carried out using a
      dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for
      future structural characterization was selected using differential scanning
      calorimetry, powder X-ray diffraction, and Fourier transform infrared
      spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats
      were studied after pulmonary administration of NRG-SLN lyophilized powder.
      Glycerol monostearate was selected to prepare SLNs, and the optimal formulation
      of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a
      polydispersity index of 0.258, a zeta potential of -31.4 mV, a total drug content
      of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours
      with a sustained profile. In addition, 5% mannitol (w/v) was screened as a
      cryoprotectant. Fourier transform infrared spectroscopy, differential scanning
      calorimetry, and powder X-ray diffraction studies confirmed that the drug was
      encapsulated into SLNs in an amorphous form. The lyophilized powder was stable at
      both refrigeration (4 degrees C) and ambient temperature (25 degrees C) for 3
      months, and the MTT assay demonstrated that the SLNs were nontoxic. The cellular
      uptake of fluorescein isothiocyanate-labeled SLNs in A549 cells was highly time
      dependent over a period of 3 hours, while the pharmacokinetic study in Sprague
      Dawley rats showed that the relative bioavailability of NRG-SLNs was 2.53-fold
      greater than that of NRG suspension after pulmonary administration. This study
      shows that SLNs offer a promising pulmonary delivery system to increase the
      bioavailability of the poorly water-soluble drug NRG. 

PMID- 27041996
TI  - Effect of picroside II on erythrocyte deformability and lipid peroxidation in
      rats subjected to hind limb ischemia reperfusion injury.
AB  - BACKGROUND: Ischemia reperfusion injury (I/R) in hind limb is a frequent and
      important clinical phenomenon. Many structural and functional damages are
      observed in cells and tissues in these kinds of injuries. In this study, we aimed
      to evaluate the effect of picroside II on lipid peroxidation and erythrocyte
      deformability during I/R in rats. METHODS: Rats were randomly divided into four
      groups - each containing six animals (sham, I/R, sham + picroside II, and I/R +
      picroside II). The infrarenal section of the abdominal aorta was occluded with an
      atraumatic microvascular clamp in I/R groups. The clamp was removed after 120
      minutes and reperfusion was provided for a further 120 minutes. Picroside II (10
      mg.kg(-1)) was administered intraperitoneally to the animals in the appropriate
      groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized
      by intraperitoneal administration of ketamine (100 mg.kg(-1)) and taking blood
      from the abdominal aorta. Erythrocytes were extracted from heparinized complete
      blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the
      filtration system and the changes in pressure were measured to investigate the
      role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and
      erythrocyte deformability index. RESULTS: Deformability index was significantly
      increased in the I/R group compared to groups sham, sham + picroside-II, and I/R
      + picroside-II (P<0.0001, P<0.0001, and P=0.007). Malondialdehyde (MDA) and NO
      levels were evaluated. MDA level and NO activity were also higher in the I/R
      group than in the other groups. Picroside II treatment before hind limb I/R
      prevented these changes. CONCLUSION: These results support that deformability of
      erythrocytes is decreased in I/R injury and picroside II plays a critical role to
      prevent these alterations. Further experimental and clinical studies are needed
      to evaluate and clarify the molecular mechanisms of action and clinical
      importance of these findings.

PMID- 27041997
TI  - Effects of Dang-Gui-Bu-Xue-Tang, an herbal decoction, on iron uptake in iron
      deficient anemia.
AB  - Dang-Gui-Bu-Xue-Tang (DBT), a combination of Angelicae Sinensis Radix and
      Astragali Radix, is a widely used herbal decoction in traditional Chinese
      medicine primarily to promote or invigorate the "blood". In this study, we
      explored this ancient formulation and provide evidence of its blood-toning
      properties. We used the improvement iron uptake as promote or invigorate the
      "blood" indicator. Ferritin formation of Caco-2 cells in vitro assay and diet
      induced anemia (DIA) in rat model were used to prove its improvement iron uptake
      and ameliorating effects. Finally, the iron-DBT interactions were measured by
      iron-binding assay. We first demonstrated DBT increased uptake of ferrous iron
      through the biosynthesis of ferritin by Caco-2 cells and determined which
      complementary treatment would provide optimum results. Thereafter, effects of the
      treatment on improving the bioavailability of absorbed iron in the form of
      hemoglobin (Hb) were established using a DIA-animal model. The results showed
      that DBT slightly improved Hb levels compared with the baseline Hb and
      pretreatment with DBT for 2 hours prior to supplementation with ferrous sulfate
      provided the greatest gain in Hb levels in DIA rats. However, DBT and ferrous
      sulfate were co-treated with Caco-2 cell or DIA rats, the ferritin formation and
      Hb levels both were decreased. In iron-binding assay, the DBT extract influenced
      the free Fe(II) type in the FeSO4 solution. Therefore, we suggest that
      complementary treatment with DBT and iron supplementation can have a strong
      ameliorating effect on iron-deficiency anemia in clinical settings, but needs a 2
      hour interval of DBT administration prior to ferrous sulfate treatment. 

PMID- 27041998
TI  - Solubility enhancement of simvastatin by arginine: thermodynamics, solute-solvent
      interactions, and spectral analysis.
AB  - We examined the solubility of simvastatin in water in 0.01 mol.dm(-3), 0.02
      mol.dm(-3), 0.04 mol.dm(-3), 0.09 mol.dm(-3), 0.18 mol.dm(-3), 0.36 mol.dm(-3),
      and 0.73 mol.dm(-3) arginine (ARG) solutions. The investigated drug is termed the
      solute, whereas ARG the cosolute. Phase solubility studies illustrated a higher
      extent of solubility enhancement for simvastatin. The aforementioned system was
      subjected to conductometric and volumetric measurements at temperatures (T) of
      298.15 K, 303.15 K, 308.15 K, and 313.15 K to illustrate the thermodynamics
      involved and related solute-solvent interactions. The conductance values were
      used to evaluate the limiting molar conductance and association constants.
      Thermodynamic parameters (DeltaG (0), DeltaH (0), DeltaS (0), and E s) for the
      association process of the solute in the aqueous solutions of ARG were
      calculated. Limiting partial molar volumes and expansibilities were evaluated
      from the density values. These values are discussed in terms of the solute
      solvent and solute-cosolute interactions. Further, these systems were analyzed
      using ultraviolet-visible analysis, Fourier-transform infrared spectroscopy, and
      (13)C, (1)H, and two-dimensional nuclear overhauser effect spectroscopy nuclear
      magnetic resonance to complement thermophysical explanation. 

PMID- 27041999
TI  - Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood
      glucose in type 1-like diabetic rats.
AB  - BACKGROUND: Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin),
      is an herb used for renal dysfunction in Chinese traditional medicine. In an
      attempt to develop this herb as a treatment for diabetic nephropathy (DN), we
      investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic
      rats. METHODS: Streptozotocin (STZ) was used to induce type 1-like diabetes in
      rats (STZ-diabetic rats). In addition to hyperglycemia, STZ-diabetic rats showed
      significant nephropathy, including higher plasma levels of blood urea nitrogen,
      creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue
      was applied to characterize the changes in potential signals related to
      nephropathy. RESULTS: Oral administration of Du-Zhong (1 g/kg/day) to STZ
      diabetic rats for 20 days not only decreased the plasma levels of blood urea
      nitrogen and creatinine but also improved renal fibrosis, whereas the plasma
      glucose level was not changed. The higher expressions of protein levels of
      transforming growth factor-beta (TGF-beta) and connective tissue growth factor in
      diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation
      of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong
      cannot reverse the hyperglycemia-induced overproduction of signal transducers and
      activators of transcription 3 in the diabetic kidney. CONCLUSION: Oral
      administration of Du-Zhong improves STZ-induced DN in rats by inhibiting TGF
      beta/Smad signaling and suppressing TGF-beta/connective tissue growth factor
      expression. Therefore, active principle from Du-Zhong is suitable to develop as
      new agent for DN in the future.

PMID- 27042000
TI  - Da0324, an inhibitor of nuclear factor-kappaB activation, demonstrates selective
      antitumor activity on human gastric cancer cells.
AB  - BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) is
      constitutively activated in a variety of human cancers, including gastric cancer.
      NF-kappaB inhibitors that selectively kill cancer cells are urgently needed for
      cancer treatment. Curcumin is a potent inhibitor of NF-kappaB activation.
      Unfortunately, the therapeutic potential of curcumin is limited by its relatively
      low potency and poor cellular bioavailability. In this study, we presented a
      novel NF-kappaB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl
      analog of curcumin. The purpose of this study is to research the expression of NF
      kappaB in gastric cancer and the antitumor activity and mechanism of Da0324 on
      human gastric cancer cells. METHODS: The expressions between gastric cancer
      tissues/cells and normal gastric tissues/cells of NF-kappaB were evaluated by
      Western blot. The inhibition viability of compounds on human gastric cancer cell
      lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line
      GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide assay. Absorption spectrum method and high-performance liquid
      chromatography method detected the stability of the compound in vitro. The
      compound-induced changes of inducible NF-kappaB activation in the SGC-7901 and
      BGC-823 cells were examined by Western blot analysis and immunofluorescence
      methods. The antitumor activity of compound was performed by clonogenic assay,
      matrigel invasion assay, flow cytometric analysis, Western blot analysis, and
      Hoechst 33258 staining assay. RESULTS: High levels of p65 were found in gastric
      cancer tissues and cells. Da0324 displayed higher growth inhibition against
      several types of gastric cancer cell lines and showed relatively low toxicity to
      GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot
      analysis and immunofluorescence methods showed that Da0324 blocked NF-kappaB
      activation. In addition, Da0324 significantly inhibited tumor proliferation and
      invasion, arrested the cell cycle, and induced apoptosis in vitro. CONCLUSION:
      The asymmetric mono-carbonyl analog of curcumin Da0324 exhibited significantly
      improved antigastric cancer activity. Da0324 may be a promising NF-kappaB
      inhibitor for the selective targeting of cancer cells. However, further studies
      are needed in animals to validate these findings for the therapeutic use of
      Da0324.

PMID- 27042001
TI  - A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development,
      pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.
AB  - 5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral
      bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion
      evaporation method. The effect of Span 80 concentration, ether/ethanol volume
      ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical
      characteristics, floating, and in vitro release behaviors of 5-FU hollow
      microspheres was investigated and optimized. The formulation and technology
      composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl
      pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch
      samples, which showed an excellent reproducibility. The microspheres were
      spherical with a hollow structure with high drug loading amount (28.4%+/-0.5%)
      and production yield (74.2%+/-0.6%); they exhibited excellent floating and
      sustained release characteristics in simulated gastric and intestinal fluid.
      Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly
      enhanced oral bioavailability (area under curve, [AUC](0-t): 12.53+/-1.65
      mg/L(*)h vs 7.80+/-0.83 and 5.82+/-0.83 mg/L(*)h) with longer elimination half
      life (t1/2) (15.43+/-2.12 hours vs 2.25+/-0.22 and 1.43+/-0.18 hours) and mean
      residence time (7.65+/-0.97 hours vs 3.61+/-0.41 and 2.34+/-0.35 hours), in
      comparison with its solid microspheres and powder. In vivo distribution results
      from tumor-bearing nude mice demonstrated that the animals administered with 5-FU
      hollow microspheres had much higher drug content in tumor, plasma, and stomach at
      1 and 8 hours except for 0.5 hours sample collection time point in comparison
      with those administered with 5-FU solid microspheres and its powder. These
      results suggested that the hollow microspheres would be a promising controlled
      drug delivery system for an oral chemotherapy agent like 5-FU. 

PMID- 27042002
TI  - Plasmodium-infected erythrocytes (pRBC) induce endothelial cell apoptosis via a
      heme-mediated signaling pathway.
AB  - Heme is cytotoxic to the plasmodium parasite, which converts it to an insoluble
      crystalline form called hemozoin (malaria pigment) in erythrocytes during
      replication. The increased serum levels of free heme cause tissue damage,
      activation of microvascular endothelial and glial cells, focal inflammation,
      activation of apoptotic pathways, and neuronal tissue damage. Several hypotheses
      have been proposed to explain how these causative factors exacerbate fatal
      malaria. However, none of them fully explain the detailed mechanisms leading to
      the high morbidity and mortality associated with malaria. We have previously
      reported that heme-induced brain microvascular endothelial cell (HBVEC) apoptosis
      is a major contributor to severe malaria pathogenesis. Here, we hypothesized that
      heme (at clinically relevant levels) induces inflammation and apoptosis in HBVEC,
      a process that is mediated by independent proinflammatory and proapoptotic
      signaling pathways. In this study, we determined the key signaling molecules
      associated with heme-mediated apoptosis in HBVEC in vitro using RT2 profiler
      polymerase chain reaction array technology and confirmed results using
      immunostaining techniques. While several expressed genes in HBVEC were altered
      upon heme stimulation, we determined that the apoptotic effects of heme were
      mediated through p73 (tumor protein p73). The results provide an opportunity to
      target heme-mediated apoptosis therapeutically in malaria-infected individuals. 

PMID- 27042003
TI  - Laquinimod in the treatment of multiple sclerosis: a review of the data so far.
AB  - Laquinimod (ABR-215062) is a new orally available carboxamide derivative, which
      is currently developed for relapsing remitting (RR) and chronic progressive (CP)
      forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative
      diseases. Its mechanism of action may comprise immunomodulatory effects on T
      cells, monocytes, and dendritic cells as well as neuroprotective effects with
      prominent actions on astrocytes. Laquinimod was tested in Phase II and III
      clinical trials in RRMS at different dosages ranging from 0.1 to 0.6 mg/day. The
      compound was well tolerated, yet at the dosages tested only led to moderate
      effects on the reduction of relapse rates as primary study endpoint in Phase III
      trials. In contrast, significant effects on brain atrophy and disease progression
      were observed. While there were no significant safety signals in the clinical
      trials, the Committee for Medicinal Products for Human Use (CHMP) refused
      marketing authorization for RRMS based on the assessment of the risk-benefit
      ratio with regard to data from animal studies. At present, the compound is
      further tested in RRMS as well as CPMS and Huntington's disease at different
      concentrations. Results from these trials will further inform about the clinical
      benefit of laquinimod in patient cohorts with a persisting, but still
      insufficiently met need for safe and at the same time effective oral compounds
      with neuroprotective effects. 

PMID- 27042004
TI  - Selective use of sorafenib in the treatment of thyroid cancer.
AB  - Sorafenib is a multiple kinase inhibitor (MKI) approved for the treatment of
      primary advanced renal cell carcinoma and advanced primary liver cancer. It was
      recently approved by several health agencies around the world as the first
      available MKI treatment for radioactive iodine-refractory advanced and
      progressive differentiated thyroid cancer. Sorafenib targets C-RAF, B-RAF, VEGF
      receptor-1, -2, -3, PDGF receptor-beta, RET, c-kit, and Flt-3. As a
      multifunctional inhibitor, sorafenib has the potential of inhibiting tumor
      growth, progression, metastasis, and angiogenesis and downregulating mechanisms
      that protect tumors from apoptosis and has shown to increase the progression-free
      survival in several Phase II trials. This led to the Phase III trial (DECISION)
      which showed that there was an improvement in progression-free survival of 5
      months for patients on sorafenib when compared to those on placebo. Adverse
      events with this drug are common but usually manageable. The development of
      resistance after 1 or 2 years is almost a rule in most patients who showed
      partial response or stabilization of the disease while on sorafenib, which makes
      it necessary to think of a plan for subsequent therapies. These may include the
      use of another MKI, such as lenvatinib, the second approved MKI for advanced
      differentiated thyroid cancer, or include patients in clinical trials or the off
      label use of other MKIs. Given sorafenib's earlier approval, most centers now
      have access to its prescription. The goal of this review was to improve the care
      of these patients by describing key aspects that all prescribers will need to
      master in order to optimize outcomes. 

PMID- 27042005
TI  - Synthesis, antimicrobial, and antiproliferative activities of substituted
      phenylfuranylnicotinamidines.
AB  - This research work deals with the design and synthesis of a series of substituted
      phenylfuranylnicotinamidines 4a-i. Facile preparation of the target compounds was
      achieved by Suzuki coupling-based synthesis of the nitrile precursors 3a-i,
      followed by their conversion to the corresponding nicotinamidines 4a-i utilizing
      LiN(TMS)2. The antimicrobial activities of the newly synthesized nicotinamidine
      derivatives were evaluated against the Gram-negative bacterial strains
      Escherichia coli and Pseudomonas aeruginosa as well as the Gram-positive
      bacterial strains Staphylococcus aureus and Bacillus megaterium. The minimum
      inhibitory concentration values of nicotinamidines against all tested
      microorganisms were in the range of 10-20 MUM. In specific, compounds 4a and 4b
      showed excellent minimum inhibitory concentration values of 10 MUM against
      Staphylococcus aureus bacterial strain and were similar to ampicillin as an
      antibacterial reference. On the other hand, selected nicotinamidine derivatives
      were biologically screened for their cytotoxic activities against a panel of 60
      cell lines representing nine types of human cancer at a single high dose at
      National Cancer Institute, Bethesda, MD, USA. Nicotinamidines showing promising
      activities were further assessed in a five-dose screening assay to determine
      their compound concentration causing 50% growth inhibition of tested cell (GI50),
      compound concentration causing 100% growth inhibition of tested cell (TGI), and
      compound concentration causing 50% lethality of tested cell (LC50) values.
      Structure-activity relationship studies demonstrated that the activity of members
      of this series can be modulated from cytostatic to cytotoxic based on the
      substitution pattern/nature on the terminal phenyl ring. The most active compound
      was found to be 4e displaying a submicromolar GI50 value of 0.83 MUM, with TGI
      and LC50 values of 2.51 and 100 MUM, respectively. Finally, the possible
      underlying mechanism of action of this series of compounds was investigated by
      determining their nuclease-like DNA degradation ability in addition to their
      antioxidant power and all monocations proved to be effective in all assays. 

PMID- 27042006
TI  - Toward antituberculosis drugs: in silico screening of synthetic compounds against
      Mycobacterium tuberculosisl,d-transpeptidase 2.
AB  - Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the
      main reason why this disease continues to be a global public health threat. It is
      therefore imperative to find a novel antitubercular drug target that is unique to
      the structural machinery or is essential to the growth and survival of the
      bacterium. One such target is the enzyme l,d-transpeptidase 2, also known as
      LdtMt2, a protein primarily responsible for the catalysis of 3->3 cross-linkages
      that make up the mycolyl-arabinogalactan-peptidoglycan complex of Mtb. In this
      study, structure-based pharmacophore screening, molecular docking, and in silico
      toxicity evaluations were employed in screening compounds from a database of
      synthetic compounds. Out of the 4.5 million database compounds, 18 structures
      were identified as high-scoring, high-binding hits with very satisfactory
      absorption, distribution, metabolism, excretion, and toxicity properties. Two out
      of the 18 compounds were further subjected to in vitro bioactivity assays, with
      one exhibiting a good inhibitory activity against the Mtb H37Ra strain. 

PMID- 27042007
TI  - Comments on a meta-analysis and systematic review of the clinicopathological
      significance of CDH1 in gastric cancer.

PMID- 27042008
TI  - Efficacy of nystatin for the treatment of oral candidiasis: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To systematically review and assess the efficacy, different treatment
      protocols (formulation, dosage, and duration), and safety of nystatin for
      treating oral candidiasis. METHODS: Four electronic databases were searched for
      trials published in English till July 1, 2015. Randomized controlled trials
      comparing nystatin with other antifungal therapies or a placebo were included.
      Clinical and/or mycological cure was the outcome evaluation. A meta-analysis or
      descriptive study on the efficacy, treatment protocols, and safety of nystatin
      was conducted. RESULTS: The meta-analysis showed that nystatin pastille was
      significantly superior to placebo in treating denture stomatitis. Nystatin
      suspension was not superior to fluconazole in treating oral candidiasis in
      infants, children, or HIV/AIDS patients. The descriptive investigations showed
      that administration of nystatin suspension and pastilles in combination for 2
      weeks might achieve a higher clinical and mycological cure rate, and using the
      nystatin pastilles alone might have a higher mycological cure rate, when compared
      with using nystatin suspensions alone. Nystatin pastilles at a dose of 400,000 IU
      resulted in a significantly higher mycological cure rate than that administrated
      at a dose of 200,000 IU. Furthermore, treatment with nystatin pastilles for 4
      weeks seemed to have better clinical efficacy than treatment for 2 weeks.
      Descriptive safety assessment showed that poor taste and gastrointestinal adverse
      reaction are the most common adverse effects of nystatin. CONCLUSION: Nystatin
      pastille was significantly superior to placebo in treating denture stomatitis,
      while nystatin suspension was not superior to fluconazole in treating oral
      candidiasis in infants, children, or HIV/AIDS patients. Indirect evidence from a
      descriptive study demonstrated that administration of nystatin pastille alone or
      pastille and suspension in combination is more effective than that of suspension
      alone; prolonged treatment duration for up to 4 weeks can increase the efficacy
      of nystatin. More well designed and high quality randomized control studies are
      needed to confirm these findings.

PMID- 27042009
TI  - Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma
      in vitro and in vivo.
AB  - PURPOSE: BIBF 1120 is a potent triple angiokinase inhibitor now being evaluated
      in many types of tumors. We examine the antitumor effects of BIBF 1120 on
      nasopharyngeal carcinoma (NPC) in vitro and in vivo. MATERIALS AND METHODS: The
      effect of BIBF 1120 on NPC cell proliferation was evaluated using the Cell
      Counting Kit 8 assay. The activities of BIBF 1120 as a single agent and in
      combination with cisplatin (DDP) in NPC tumor xenografts were evaluated by
      measuring microvessel density and expression of vascular endothelial growth
      factor signaling. RESULTS: BIBF 1120 exhibited limited inhibition of the growth
      of three NPC cell lines. Concurrent administration of BIBF 1120 and DDP provided
      greater antitumor effects compared to that observed with the use of either
      inhibitor as a single agent in the NPC xenograft model. Microvessel density and
      expression of vascular endothelial growth factor signaling were significantly
      reduced. CONCLUSION: BIBF 1120, either as a single agent or in combination with
      DDP, demonstrates significant antitumor and antiangiogenic effects in the NPC
      xenograft model. Our results indicate that BIBF 1120 administered in conjunction
      with chemotherapy might provide an effective treatment method for NPC.

PMID- 27042010
TI  - Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces
      cell cycle arrest and apoptosis in gastric cancer.
AB  - Cyclin-dependent kinase (CDK) family members have been considered as attractive
      therapeutic targets for cancer. In this study, we aim to investigate the
      anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC)
      cell line. Human GC cells (BGC823) were cultured with or without BS-181 at
      different concentrations for 24-72 hours. BS-181 significantly reduced the
      activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment
      with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and
      caspase-3 was significantly increased, while Bcl-2 expression was decreased in
      cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181
      resulted in reduced rates of proliferation, migration, and invasion of gastric
      cells. Those results demonstrated the anticancer activities of selective CDK7
      inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel
      therapeutic target or the treatment of GC. 

PMID- 27042011
TI  - Erratum: Sonodynamic effect of hematoporphyrin monomethyl ether on ligature
      induced periodontitis in rats [Corrigendum].

PMID- 27042012
TI  - Computational and nonglycosylated systems: a simpler approach for development of
      nanosized PEGylated proteins.
AB  - Cysteine PEGylation includes several steps, and is difficult to manage in
      practice. In the current investigation, the cysteine PEGylation of erythropoietin
      analogs was examined using computational and nonglycosylated systems to define a
      simpler approach for specific PEGylation. Two model analogs (E31C and E89C) were
      selected for PEGylation based on lowest structural deviation from the native
      form, accessibility, and nucleophilicity of the free thiol group. The selected
      analogs were cloned and the expression was assessed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blot using Coomassie blue staining
      and anti-His monoclonal antibody, respectively. PEGylation with 20 kDa mPEG
      maleimide resulted in 79% and 82% conjugation yield for E31C and E89C
      nonglycosylated erythropoietin (ngEPO) analogs, respectively. The size
      distribution and charge analysis showed an increase in size and negative charge
      of the PEGylated forms compared with nonconjugated ones. Biological assay
      revealed that E31C and E89C mutations and subsequent PEGylation of ngEPO analogs
      have no deleterious effects on in vitro biological activity when compared to CHO
      derived recombinant human erythropoietin. In addition, PEG-conjugated ngEPOs
      showed a significant increase in plasma half-lives after injection into rats when
      compared to nonconjugated ones. The development of the cysteine-PEGylated
      proteins using nonglycosylated expression system and in silico technique can be
      considered an efficient approach in terms of optimization of PEGylation
      parameters, time, and cost. 

PMID- 27042013
TI  - Regional differences in hepatitis C treatment with peginterferon and ribavirin in
      Japan: a retrospective cohort study.
AB  - PURPOSE: The aims of this study were to investigate regional differences in
      hepatitis C virus (HCV) infection treatment with peginterferon and ribavirin in
      Japan and to develop and validate statistical models for analysis of regional
      differences, using generalized linear mixed models. METHODS: Individuals with
      chronic HCV infection were identified from the Japanese Interferon Database
      (registered from December 2009 to April 2013). The total sustained virologic
      response rate and the rate in each prefecture were calculated. In the analysis
      using generalized linear mixed models, the following four models were
      constructed: 1) prefecture as a fixed effect, 2) prefecture and other confounding
      variables as fixed effects, 3) prefecture as a random effect, and 4) prefecture
      as a random effect and other confounding variables as fixed effects. The quality
      of the model fit was assessed using the Akaike information criterion and the
      Bayesian information criterion. All statistical analyses were performed using SAS
      Version 9.4 for Windows. RESULTS: From 36 prefectures, 16,349 cases were recorded
      in the study period. Of these, 4,677 were excluded according to certain criteria.
      The total sustained virologic response rate was 59.9% (range, 43.9%-71.6%). The
      statistical model including prefecture as a random effect and other confounding
      variables as fixed effects showed the best fit based on the Akaike information
      criterion (13,830.92) and Bayesian information criterion (13,845.17). CONCLUSION:
      Regional differences may exist in HCV infection treatment in Japan. The model
      including prefecture as a random effect and other confounding variables as fixed
      effects was appropriate for analysis of such regional differences. Additional
      studies considering the medical situations of each patient would provide useful
      information that could contribute to improve and standardize HCV infection
      treatment.

PMID- 27042014
TI  - The renoprotective effects of sulodexide.

PMID- 27042015
TI  - Zolav((r)) (a p-carboethoxy-tristyrylbenzene derivative) [corrected]: a new
      antibiotic for the treatment of acne.
AB  - BACKGROUND: Acne is a prominent skin condition affecting >80% of teenagers and
      young adults and ~650 million people globally. Isotretinoin, a vitamin A
      derivative, is currently the standard of care for treatment. However, it has a
      well-established teratogenic activity, a reason for the development of novel and
      low-risk treatment options for acne. OBJECTIVE: To investigate the effectiveness
      of Zolav((r)), (a p-carboethoxy-tristyrylbenzene derivative) [corrected] a novel
      antibiotic as a treatment for acne vulgaris. MATERIALS AND METHODS: Minimum
      inhibitory concentration of Zolav((r)) (a p-carboethoxy-tristyrylbenzene
      derivative) against Propionibacterium acnes was determined by following a
      standard protocol using Mueller-Hinton broth and serial dilutions in a 96-well
      plate. Cytotoxicity effects on human umbilical vein endothelial cells and lung
      cells in the presence of Zolav((r)) (a p-carboethoxy-tristyrylbenzene derivative)
      were investigated by determining the growth inhibition (GI50) concentration,
      total growth inhibition concentration, and the lethal concentration of 50%
      (LC50). The tryptophan auxotrophic mutant of Escherichia coli strain, WP2 uvrA
      (ATCC 49979), was used for the AMES assay with the addition of Zolav((r)) (a p
      carboethoxy-tristyrylbenzene derivative) tested for its ability to reverse the
      mutation and induce bacterial growth. The in vivo effectiveness of Zolav((r)) (a
      p-carboethoxy-tristyrylbenzene derivative) was tested in a P. acnes mouse
      intradermal model where the skin at the infection site was removed, homogenized,
      and subjected to colony-forming unit (CFU) counts. RESULTS: Susceptibility
      testing of Zolav((r)) (a p-carboethoxy-tristyrylbenzene derivative) against P.
      acnes showed a minimum inhibitory concentration of 2 ug/mL against three strains
      with no cytotoxicity and no mutagenicity observed at the highest concentrations
      tested, 30 uM and 1,500 ug/plate, respectively. The use of Zolav((r)) (a p
      carboethoxy-tristyrylbenzene derivative) at a concentration of 50 ug/mL (q8h)
      elicited a two-log difference in CFU/g between the treatment group and the
      control. CONCLUSION: This study demonstrates the potential of Zolav((r)) (a p
      carboethoxy-tristyrylbenzene derivative) as a novel treatment for acne vulgaris.

PMID- 27042016
TI  - A set of four simple performance measures reflecting adherence to guidelines
      predicts hospitalization: a claims-based cohort study of patients with diabetes.
AB  - BACKGROUND: The link between guideline adherence and outcomes is a highly
      demanded issue in diabetes care. We aimed to assess the adherence to guidelines
      and its impact on hospitalization using a simple set of performance measures
      among patients with diabetes. METHODS: We performed a retrospective cohort study,
      using health care claims data for adult patients with treated diabetes (2011
      2013). Patients were categorized into three drug treatment groups (with oral
      antidiabetic agents [OAs] only, in combination with insulin, and insulin only).
      Performance measures were based on international established guidelines for
      diabetes care. Multivariate logistic regression models predicted the probability
      of hospitalization (2013) by adherence level (2011) among all treatment groups.
      RESULTS: A total of 40,285 patients with diabetes were enrolled in 2011.
      Guideline adherence was quite low: about 70% of all patients received a biannual
      hemoglobin A1c measurement and 19.8% had undergone an annual low-density
      lipoprotein cholesterol test. Only 4.8% were exposed to full adherence including
      all performance measures (OAs: 3.7%; insulin: 7.7%; and in combination: 7.2%).
      Increased guideline adherence was associated with decreased probability of
      hospitalization. This effect was strongest in patients using OAs and insulin in
      combination. CONCLUSION: Our study showed that measures to reflect physicians'
      guideline adherence in diabetes care can easily be calculated based on already
      available datasets. Furthermore, these measures are clearly linked with the
      probability of hospitalization suggesting that a better guideline adherence by
      physicians could help to prevent a large number of hospitalizations.

PMID- 27042017
TI  - The association between cognitive function and objective adherence to dietary
      sodium guidelines in patients with heart failure.
AB  - BACKGROUND: Although cognitive impairment is common in heart failure (HF)
      patients, its effects on sodium adherence recommendations are unknown. PURPOSE:
      Our aim is to examine if cognitive function is associated with patient sodium
      adherence. METHODS: Sodium collection/excretion and cognitive function were
      assessed for 339 HF patients over a 5-8-week period. Neuropsychological testing
      was performed at baseline (Visit 1), whereas two 24-hour urine samples were
      collected within 7 weeks postbaseline. The ability to collect two 24-hour urine
      samples and the estimation of sodium excretion levels from these samples were
      used to estimate sodium adherence recommendations. RESULTS: Nearly half (47%) of
      the study participants (n=159) were unable to give two valid 24-hour urine
      samples. Participants who were unable to adhere to two valid 24-hour urine
      samples had significantly poorer attention and global cognition tests (P<0.044),
      with a trend for poorer executive function (P=0.064). Among those with valid
      samples, urine sodium level was not associated with global cognitive function,
      attention, executive function, or memory after adjusting for covariates. Female
      sex was associated with lower sodium excretion (all P<0.01); individuals with
      knowledge of sodium guidelines had less intake of sodium, resulting in excretion
      of less sodium (all P<=0.03). Conversely, higher socioeconomic status (SES) and
      body mass index (BMI) were associated with greater sodium (all P<=0.02 and
      P<=0.01). CONCLUSION: Adherence to urine sodium collection was poor, especially
      among those with poorer cognitive function. Sodium consumption exceeded
      recommended amounts and was unrelated to cognitive function. Interventions for
      improving sodium adherence should focus on at-risk groups (high SES and BMI) and
      at improving knowledge of recommended salt intake.

PMID- 27042018
TI  - The interactive web-based program MSmonitor for self-management and
      multidisciplinary care in multiple sclerosis: utilization and valuation by
      patients.
AB  - BACKGROUND: MSmonitor is an interactive web-based program for self-management and
      integrated, multidisciplinary care in multiple sclerosis. METHODS: To assess the
      utilization and valuation by persons with multiple sclerosis, we held an online
      survey among those who had used the program for at least 1 year. We evaluated the
      utilization and meaningfulness of the program's elements, perceived use of data
      by neurologists and nurses, and appreciation of care, self-management, and
      satisfaction. RESULTS: Fifty-five persons completed the questionnaire (estimated
      response rate 40%). The Multiple Sclerosis Impact Profile (MSIP), Medication and
      Adherence Inventory, Activities Diary, and electronic consultation (e-consult)
      were used by 40%, 55%, 47%, and 44% of respondents and were considered meaningful
      by 83%, 81%, 54%, and 88%, respectively. During out-patient consultations, nurses
      reportedly used the MSmonitor data three to six times more frequently than
      neurologists. As to nursing care, more symptoms were dealt with (according to 54%
      of respondents), symptoms were better discussed (69%), and the overall quality of
      care had improved (60%) since the use of the program. As to neurological care,
      these figures were 24%, 31%, and 27%, respectively. In 46% of the respondents,
      the insight into their symptoms and disabilities had increased since the use of
      the program; the MSIP, Activities Diary, and e-consult had contributed most to
      this improvement. The overall satisfaction with the program was 3.5 out of 5, and
      73% of the respondents would recommend the program to other persons with multiple
      sclerosis. CONCLUSION: A survey among persons with multiple sclerosis using the
      MSmonitor program showed that the MSIP, Medication and Adherence Inventory,
      Activities Diary, and e-consult were frequently used and that the MSIP,
      Medication and Adherence Inventory, and e-consult were appreciated the most.
      Moreover, the quality of nursing care, but not so neurological care, had
      improved, which may relate to nurses making more frequent use of the MSmonitor
      data than neurologists.

PMID- 27042019
TI  - Prediction of pain in orthodontic patients based on preoperative pain assessment.
AB  - AIM: To investigate whether pretreatment assessment of experimental pain can
      predict the level of pain after archwire placement. METHODS: One hundred and
      twenty-one general university students seeking orthodontic treatment were
      enrolled in this study. A cold pressor test was performed to estimate the pain
      tolerance of subjects before treatment. Self-reported pain intensity was
      calculated using a 10 cm visual analog scale during the 7 days after treatment.
      The relationship between pain tolerance and orthodontic pain was analyzed using
      Spearman's correlation analysis. RESULTS: The maximum mean level of pain
      intensity occurred at 24 hours after bonding (53.31+/-16.13) and fell to normal
      levels at day 7. Spearman's correlation analysis found a moderate positive
      association between preoperative pain tolerance and self-reported pain after
      archwire placement (P<0.01). There was no significant difference in pain
      intensity between male and female patients at any time point (P>0.05).
      CONCLUSION: A simple and noninvasive preoperative sensory test (the cold pressor
      test) was useful in predicting the risk of developing unbearable pain in patients
      after archwire placement. Self-reported pain after archwire placement decreased
      as individual pain tolerance increased.

PMID- 27042020
TI  - Influence of structured telephone follow-up on patient compliance with
      rehabilitation after total knee arthroplasty.
AB  - INTRODUCTION: To assess the effects of structured telephone follow-up on
      patient's home-exercise compliance after total knee arthroplasty (TKA). METHODS:
      A total of 202 elderly patients who received a unilateral TKA were enrolled in
      this study. The participants were randomized into two groups: the intervention
      group that received structured telephone follow-up after discharge and the
      control group that received routine health care. Pain, functional ability,
      quality of life, and depression survey scores were measured before and after TKA.
      The intergroup and intragroup differences were analyzed during the 12 months
      following discharge. RESULTS: There were no significant differences in the
      sociodemographic characteristics of both groups. The mean home-exercise time and
      total days in the intervention group were significantly higher than those in the
      control group. Variable scores differed significantly between groups. Pain,
      functional ability, quality of life, and depression improved significantly after
      TKA in both groups, and the intervention group had greater improvement in mental
      health and active range of motion. CONCLUSION: Undergoing a TKA can significantly
      reduce the patient's pain from osteoarthritis while improving the overall
      physical function and quality of life. Furthermore, a structured telephone follow
      up can improve patient adherence to home exercise after TKA.

PMID- 27042021
TI  - The outcomes of intra-aortic balloon pump usage in patients with acute myocardial
      infarction: a comprehensive meta-analysis of 33 clinical trials and 18,889
      patients.
AB  - BACKGROUND: The effects of intra-aortic balloon pump (IABP) usage in patients
      with acute myocardial infarction remain controversial. This study sought to
      evaluate the outcomes of IABP usage in these patients. METHODS: Medline, EMBASE,
      and other internet sources were searched for relevant clinical trials. The
      primary efficacy endpoints (in-hospital, midterm, and long-term mortality) and
      secondary endpoints (reinfarction, recurrent ischemia, and new heart failure in
      the hospital) as well as safety endpoints (severe bleeding requiring blood
      transfusion and stroke in-hospital) were subsequently analyzed. RESULTS: Thirty
      three clinical trials involving 18,889 patients were identified. The risk of long
      term mortality in patients suffering from acute myocardial infarction was
      significantly decreased following IABP use (odds ratio [OR] 0.66, 95% confidence
      interval [CI]: 0.48-0.91, P=0.010). Both in-hospital and midterm mortality did
      not differ significantly between the IABP use group and no IABP use group (in
      hospital: OR 0.87, 95% CI: 0.59-1.28, P=0.479; midterm: OR 1.12, 95% CI: 0.53
      2.38, P=0.768). IABP insertion was not associated with the risk reduction of
      reinfarction, recurrent ischemia, or new heart failure. However, IABP use
      increased the risk of severe bleeding requiring blood transfusion (OR 2.05, 95%
      CI: 1.29-3.25, P=0.002) and stroke (OR 1.71, 95% CI: 1.04-2.82, P=0.035). In the
      thrombolytic therapy and cardiogenic shock subgroups, reduced mortality rates
      following IABP use were observed. CONCLUSION: IABP insertion is associated with
      feasible benefits with respect to long-term survival rates in patients suffering
      from acute myocardial infarction, particularly those suffering from cardiogenic
      shock and receiving thrombolytic therapy, but at the cost of higher incidence of
      severe bleeding and stroke.

PMID- 27042022
TI  - Interleukin-18 and miR-130a in severe sepsis patients with thrombocytopenia.
AB  - BACKGROUND: Thrombocytopenia is one of the most common laboratory abnormalities
      encountered in patients with severe sepsis. It has been reported that
      thrombocytopenia is linked to mortality in patients with severe sepsis. However,
      the mechanism of thrombocytopenia in sepsis is unknown. We hypothesized that
      inflammatory cytokines and microRNAs (miRNAs) are not only involved in the
      pathogenesis of sepsis, but also are correlated with thrombocytopenia. PATIENTS
      AND METHODS: Eligible patients with severe sepsis were prospectively recruited
      and treated at our hospital between June 2012 and May 2014. The miRNA and protein
      expression of interleukin (IL)-18 and IL-27 were detected by real-time polymerase
      chain reaction and enzyme-linked immunosorbent assay, respectively. The
      expression of miR-130a and miR-150 was detected by TaqMan real-time polymerase
      chain reaction. RESULTS: Sixty eligible patients were divided into two groups: 28
      severe sepsis patients with thrombocytopenia and 32 severe sepsis patients
      without thrombocytopenia. The results demonstrated that the miRNA expression and
      plasma concentration of IL-18 in severe sepsis patients with thrombocytopenia
      were higher than those in severe sepsis patients without thrombocytopenia
      (P=0.015 and P=0.034, respectively), and miR-130a expression was significantly
      lower in severe sepsis patients with thrombocytopenia (P<0.003). CONCLUSION: Our
      data demonstrate that severe sepsis patients with thrombocytopenia have increased
      plasma and miRNA expression levels of IL-18 and decreased expression of miR-130a,
      suggesting that IL-18 and miR-130a might be involved in the pathophysiological
      process of severe sepsis with thrombocytopenia.

PMID- 27042023
TI  - Psychometric properties of the Chinese version of the Self-Efficacy for
      Appropriate Medication Use Scale in patients with stroke.
AB  - BACKGROUND: It has been reported that stroke has a higher incidence and mortality
      rate in the People's Republic of China compared to the global average. These
      conditions can be managed by proper medication use, but ensuring medication
      adherence is challenging. OBJECTIVE: To translate the Self-Efficacy for
      Appropriate Medication Use Scale into Chinese and test its validity and
      reliability in patients with stroke. METHODS: Instrument performances were
      measured from January 15, 2015 to April 28, 2015 on a convenience sample of 400
      patients with stroke recruited at four neurology departments of the First
      Affiliated Hospital of Zhengzhou University. Questionnaires included the Chinese
      versions of the Self-Efficacy for Appropriate Medication Use Scale (C-SEAMS) and
      the General Self-Efficacy Scale (C-GSE). Construct validity, convergent validity,
      internal consistency, and test-retest reliability were measured. RESULTS: Item
      analysis showed that item-to-total correlations were in the range of 0.362-0.672.
      Exploratory factor analysis revealed two factors (which accounted for 60.862% of
      total variance), with factor loading ranging from 0.534 to 0.756. Confirmatory
      factor analysis was performed to support the results, with an acceptable fit (chi
      (2)=73.716; df=64; P<0.01; goodness-of-fit index =0.902; adjusted goodness-of-fit
      index =0.897; comparative fit index =0.865; root-mean-square error of
      approximation =0.058). The convergent validity of the C-SEAMS correlated well
      with the validated measure of the C-GSE in measuring self-efficacy (r=0.531,
      P<0.01). Good internal consistency (Cronbach's alpha ranged from 0.826 to 0.915)
      and test-retest reliability (Pearson's correlation coefficient r=0.642, P<0.01)
      were found. CONCLUSION: The C-SEAMS is a brief and psychometrically sound measure
      for evaluating self-efficacy for medication adherence in the Chinese population
      with stroke.

PMID- 27042024
TI  - Facilitators and barriers to antiretroviral therapy adherence among adolescents
      in Ghana.
AB  - INTRODUCTION: Adherence to antiretroviral therapy (ART) is known to be
      challenging among adolescents living with HIV/AIDS, notwithstanding the life
      saving importance of this therapy. Of the global total number of adolescents
      living with HIV in 2013, 83% reside in sub-Saharan Africa. The study aimed to
      identify facilitators of and barriers to antiretroviral treatment adherence among
      adolescents in Ghana. METHODS: A cross-sectional qualitative study using semi
      structured interviews for data collection was carried out among adolescents (aged
      12-19 years) at the adolescents HIV clinic at the Korle-Bu Teaching Hospital in
      Ghana. Predominantly open-ended questions relating to ART were used. Interviews
      were done until saturation. In total, 19 interviews were conducted. Analysis was
      done manually to maintain proximity with the text. FINDINGS: The main
      facilitators were support from health care providers, parental support, patient's
      knowledge of disease and self-motivation, patient's perceived positive outcomes,
      and dispensed formulation. The identified barriers were patient's forgetfulness
      to take medicines, perceived stigmatization due to disclosure, financial
      barriers, and adverse effects of ART. Support from health care workers was the
      most frequently mentioned facilitator, and patient's forgetfulness and perceived
      stigmatization after disclosure were the most frequently mentioned barriers. Self
      motivation (knowledge induced) to adhere to treatment was a specific facilitator
      among older adolescents. CONCLUSION: Continuous information provision in addition
      to unflinching support from health care workers and parents or guardians may
      improve adherence among adolescents. Also, interventions to reduce patient
      forgetfulness may be beneficial. A multi-sectorial approach would be needed to
      address adolescent disclosure of HIV/AIDS status.

PMID- 27042025
TI  - Quality of pharmaceutical care at the pharmacy counter: patients' experiences
      versus video observation.
AB  - INTRODUCTION: Consumer Quality Index questionnaires are used to assess quality of
      care from patients' experiences. OBJECTIVE: To provide insight into the agreement
      about quality of pharmaceutical care, measured both by a patient questionnaire
      and video observations. METHODS: Pharmaceutical encounters in four pharmacies
      were video-recorded. Patients completed a questionnaire based upon the Consumer
      Quality Index Pharmaceutical Care after the encounter containing questions about
      patients' experiences regarding information provision, medication counseling, and
      pharmacy staff's communication style. An observation protocol was used to code
      the recorded encounters. Agreement between video observation and patients'
      experiences was calculated. RESULTS: In total, 109 encounters were included for
      analysis. For the domains "medication counseling" and "communication style",
      agreement between patients' experiences and observations was very high (>90%).
      Less agreement (45%) was found for "information provision", which was rated more
      positive by patients compared to the observations, especially for the topic,
      encouragement of patients' questioning behavior. CONCLUSION: A questionnaire is
      useful to assess the quality of medication counseling and pharmacy staff's
      communication style, but might be less suitable to evaluate information provision
      and pharmacy staff's encouragement of patients' questioning behavior. Although
      patients may believe that they have received all necessary information to use
      their new medicine, some information on specific instructions was not addressed
      during the encounter. When using questionnaires to get insight into information
      provision, observations of encounters are very informative to validate the
      patient questionnaires and make necessary adjustments.

PMID- 27042026
TI  - Aging-associated oxidized albumin promotes cellular senescence and endothelial
      damage.
AB  - Increased levels of oxidized proteins with aging have been considered a
      cardiovascular risk factor. However, it is unclear whether oxidized albumin,
      which is the most abundant serum protein, induces endothelial damage. The results
      of this study indicated that with aging processes, the levels of oxidized
      proteins as well as endothelial microparticles release increased, a novel marker
      of endothelial damage. Among these, oxidized albumin seems to play a principal
      role. Through in vitro studies, endothelial cells cultured with oxidized albumin
      exhibited an increment of endothelial damage markers such as adhesion molecules
      and apoptosis levels. In addition, albumin oxidation increased the amount of
      endothelial microparticles that were released. Moreover, endothelial cells with
      increased oxidative stress undergo senescence. In addition, endothelial cells
      cultured with oxidized albumin shown a reduction in endothelial cell migration
      measured by wound healing. As a result, we provide the first evidence that
      oxidized albumin induces endothelial injury which then contributes to the
      increase of cardiovascular disease in the elderly subjects. 

PMID- 27042027
TI  - Physical frailty, disability, and dynamics in health perceptions: a preliminary
      mediation model.
AB  - PURPOSE: Frailty is a condition characterized by loss of functional reserve and
      altered homeostatic capacity. The aging process is related with complex
      indicators of physiological state. This study aims, with a preliminary mediation
      model, to reveal the possible role of mediator of health perceptions variability
      in the relationship between frailty and disability. PATIENTS AND METHODS: A
      longitudinal study (100 days) was performed. Data from 92 institutionalized older
      adults were used in the analysis. Frailty was assessed in baseline using the
      Italian version of the Survey of Health, Ageing and Retirement in Europe -
      Frailty Instrument; health perceptions were assessed on a daily basis by three
      visual analog scale questions; and disability was measured in baseline and post
      test using the Katz Activities of Daily Living questionnaire. The product-of
      coefficient mediation approach was used to test direct and indirect effects of
      frailty. RESULTS: Results showed that daily variability of health perceptions
      plays the role of mediator between frailty and disability. In all the steps,
      statistically significant results were found. CONCLUSION: This preliminary result
      may indicate that physical frailty increases the variability in health
      perceptions contributing to disability.

PMID- 27042028
TI  - Changes of deceleration and acceleration capacity of heart rate in patients with
      acute hemispheric ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Autonomic dysfunction is common after stroke, which is
      correlated with unfavorable outcome. Phase-rectified signal averaging is a newly
      developed technique for assessing cardiac autonomic function, by detecting
      sympathetic and vagal nerve activity separately through calculating acceleration
      capacity (AC) and deceleration capacity (DC) of heart rate. In this study, we
      used this technique for the first time to investigate the cardiac autonomic
      function of patients with acute hemispheric ischemic stroke. METHODS: A 24-hour
      Holter monitoring was performed in 63 patients with first-ever acute ischemic
      stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk
      of stroke. DC, AC, heart rate variability parameters, standard deviation of all
      normal-to-normal intervals (SDNN), and square root of the mean of the sum of the
      squares of differences between adjacent normal-to-normal intervals (RMSSD) were
      calculated. The National Institutes of Health Stroke Scale (NIHSS) was used to
      assess the severity of stroke. We analyzed the changes of DC, AC, SDNN, and RMSSD
      and also studied the correlations between these parameters and NIHSS scores.
      RESULTS: The R-R (R wave to R wave on electrocardiogram) intervals, DC, AC, and
      SDNN in the cerebral infarction group were lower than those in controls (P=0.003,
      P=0.002, P=0.006, and P=0.043), but the difference of RMSSD and the D-value and
      ratio between absolute value of AC (|AC|) and DC were not statistically
      significant compared with those in controls. The DC of the infarction group was
      significantly correlated with |AC|, SDNN, and RMSSD (r=0.857, r=0.619, and
      r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that
      DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=-0.279, r=
      0.266, and r=-0.319; P=0.027, P=0.035, and P=0.011). CONCLUSION: Both DC and AC
      of heart rate decreased in patients with hemispheric infarction, reflecting a
      decrease in both vagal and sympathetic modulation. Both DC and AC were correlated
      with the severity of stroke.

PMID- 27042029
TI  - The clinical outcomes of oldest old patients with tuberculosis treated by
      regimens containing rifampicin, isoniazid, and pyrazinamide.
AB  - OBJECTIVES: To investigate the clinical characteristics, adverse drug reactions,
      and outcomes of the oldest old patients (aged >=80 years) with tuberculosis (TB)
      treated with rifampicin, isoniazid, and pyrazinamide (RIP)-containing regimens.
      DESIGN: A retrospective chart review study. SETTING: A 1,200-bed tertiary
      teaching hospital in southwest Taiwan. PARTICIPANTS: We conducted a retrospective
      observational study between January 1, 2005 and December 31, 2011. Seven hundred
      adult patients (aged >=18 years) with TB treated with RIP-containing anti-TB
      regimens were reviewed, including 161 oldest old patients. OUTCOME MEASURES:
      Clinical outcomes included clinical responsiveness and microbiological
      eradication. Adverse outcomes included drug-induced hepatitis, and other symptoms
      included gastrointestinal upset (eg, abdominal pain, vomiting, diarrhea, or
      dyspepsia), skin rash, joint pain, and hyperuricemia. RESULTS: Compared with the
      non-oldest old adult patients, the oldest old patients more frequently had
      hepatitis (P=0.014), gastrointestinal upset (P=0.029), and unfavorable outcomes
      (P<0.001). In a multivariate analysis, hepatitis during treatment (adjusted odds
      ratio: 3.482, 95% confidence interval: 1.537-7.885; P<0.003) and oldest old age
      (adjusted odds ratio: 5.161, 95% confidence interval: 2.294-11.613; P<0.010) were
      independent risk factors for unfavorable outcomes. In the oldest old patients
      with hepatitis, rifampicin use was more common in the favorable outcome group
      than in the unfavorable outcome group (100% vs 37.5%; P=0.001). CONCLUSION: The
      oldest old age and hepatitis during RIP treatment were associated with
      unfavorable outcomes. For the oldest old patients with TB having hepatitis during
      treatment, rifampicin rechallenge and use might benefit the treatment outcome.

PMID- 27042030
TI  - Effectiveness and safety of oxycodone/naloxone in the management of chronic pain
      in patients with systemic sclerosis with recurrent digital ulcers: two case
      reports.
AB  - Digital ulcers (DUs) are a severe and frequent clinical feature of patients with
      systemic sclerosis (SSc). The presence of DUs may cause severe pain and often
      lead to impairment of patient's functional activities and health-related quality
      of life. Moreover, poor patient cooperation during the wound care procedure due
      to pain may be associated with a negative outcome of DU healing. Therefore, pain
      management has a key role in patients with SSc. These two case reports describe
      the effectiveness and safety of oxycodone/naloxone in patients with SSc
      complicated by painful chronic DUs. Such a therapy has provided pain relief and
      consequently an increased compliance during redressing wounds. 

PMID- 27042031
TI  - Age as an independent factor for the development of neuropathy in diabetic
      patients.
AB  - Population aging is unprecedented, without parallel in the history of humanity.
      As type 2 diabetes mellitus is predominantly more prevalent in aging populations,
      this creates a major public health burden. Older adults with diabetes have the
      highest rates of major lower-extremity amputation, myocardial infarction, visual
      impairment, and end-stage renal disease of any age group. The aims of our study
      were to assess whether age is an independent factor for the occurrence of
      diabetic neuropathy (DN), and to evaluate the relationship between the presence
      and the severity of DN and the diabetes duration and blood glucose level. In this
      study, we enrolled 198 patients, previously diagnosed with type 2 diabetes
      mellitus. For all patients, we measured hemoglobin A1c (HbA1c), lipid profile,
      and body mass index and we assessed the presence and severity of DN using the
      evaluation of clinical signs and symptoms. Patients had a median age of 62 years,
      with a median of diabetes duration of 7 years; 55.1% of the patients were men and
      the average HbA1c in the cohort was 8.2%. The prevalence of DN according to
      Michigan Neuropathy Screening Instrument was 28.8%, being significantly and
      positively correlated with higher age (65 vs 59 years; P=0.001) and HbA1c (8.6%
      vs 8.0%; P=0.027). No significant correlations were observed between the severity
      of DN and diabetes duration, body mass index (31.9 vs 29.9 kg/m(2)), or the
      number of centimeters exceeding the normal waist circumference (25.2 vs 17.3 cm;
      P=0.003). In conclusion, age influences the presence of DN, independent on other
      risk factors. This influence persists even after adjusting for other, very
      important risk factors, like blood glucose level or diabetes duration. 

PMID- 27042032
TI  - Impact of aging on cardiac function in a female rat model of menopause: role of
      autonomic control, inflammation, and oxidative stress.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of aging on
      metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress
      parameters after ovarian hormone deprivation (OVX). METHODS: Female Wistar rats
      (3 or 22 months old) were divided into: young controls, young ovariectomized, old
      controls, and old ovariectomized (bilateral ovaries removal). After a 9-week
      follow-up, physical capacity, metabolic parameters, and morphometric and cardiac
      functions were assessed. Subsequently, arterial pressure was recorded and cardiac
      autonomic control was evaluated. Oxidative stress was measured on the cardiac
      tissue, while inflammatory profile was assessed in the plasma. RESULTS: Aging or
      OVX caused an increase in body and fat weight and triglyceride concentration and
      a decrease in both insulin sensitivity and aerobic exercise capacity. Left
      ventricular diastolic dysfunction and increased cardiac overload (myocardial
      performance index) were reported in old groups when compared with young groups.
      Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower
      only for the old groups. Tumor necrosis factor-alpha and interleukin-6 were
      increased in old groups when compared with young groups. Glutathione redox
      balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old
      ovariectomized groups when compared with young controls, indicating an increased
      oxidative stress. A negative correlation was found between GSH/GSSG and tumor
      necrosis factor-alpha (r=-0.6, P<0.003). Correlations were found between
      interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7,
      P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65,
      P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55,
      P<0.003). The findings in this trial showed that ovariectomy aggravated the
      impairment of cardiac and functional effects of aging in female rats, probably
      associated with exacerbated autonomic dysfunction, inflammation, and oxidative
      stress.

PMID- 27042033
TI  - Analysis of the relationships between edentulism, periodontal health, body
      composition, and bone mineral density in elderly women.
AB  - OBJECTIVE: The relationship between bone mineral density (BMD) and tooth loss in
      conjunction with periodontal disease is not clear. The suggested effects include
      alteration in bone remodeling rates as well as the multifaceted etiology of
      edentulism. There is also a question if other body-related variables besides BMD,
      such as body composition, may be associated with tooth number and general
      periodontal health. The aim of this study was to evaluate if tooth number and
      marginal periodontal status are associated with body composition and BMD in a
      sample of elderly women. MATERIALS AND METHODS: The study involved 91
      postmenopausal women. Data included basic anthropometric characteristics, body
      composition via bioelectrical impedance analysis, and BMD analysis at the distal
      end of the radial bone of the nondominant arm via peripheral dual-energy X-ray
      absorptiometry. A dental examination was performed to assess tooth number,
      periodontal pocket depth (PD), and gingival bleeding. RESULTS: In nonosteoporotic
      women, a significant positive correlation was found between BMD and lean body
      mass, total body water, and muscle mass. The indicators of bone metabolism
      correlated negatively with PD. Such relationships did not appear in osteoporotic
      women. In both groups, basic anthropometric characteristics and body composition
      were significantly and positively correlated with PD and bleeding on probing.
      CONCLUSION: The results suggest that body composition and BMD are not
      significantly correlated with tooth number and gingival bleeding.

PMID- 27042034
TI  - Validity of COPD diagnoses reported through nationwide health insurance systems
      in the People's Republic of China.
AB  - BACKGROUND: COPD is the fourth leading cause of death worldwide, with
      particularly high rates in the People's Republic of China, even among never
      smokers. Large population-based cohort studies should allow for reliable
      assessment of the determinants of diseases, which is dependent on the quality of
      disease diagnoses. We assessed the validity of COPD diagnoses collected through
      electronic health records in the People's Republic of China. METHODS: The CKB
      study recruited 0.5 million adults aged 30-79 years from ten diverse regions in
      the People's Republic of China during the period 2004-2008. During 7 years of
      follow-up, 11,800 COPD cases were identified by linkage with mortality registries
      and the national health insurance system. We randomly selected ~10% of the
      reported COPD cases and then undertook an independent adjudication of retrieved
      hospital medical records in 1,069 cases. RESULTS: Overall, these 1,069 cases were
      accrued over a 9-year period (2004-2013) involving 153 hospitals across ten
      regions. A diagnosis of COPD was confirmed in 911 (85%) cases, corresponding to a
      positive predictive value of 85% (95% confidence interval [CI]: 83%-87%), even
      though spirometry testing was not widely used (14%) in routine hospital care. The
      positive predictive value for COPD did not vary significantly by hospital ranking
      or calendar period, but was higher in men than women (89% vs 79%), at age >=70
      years than in younger people (88%, 95% CI: 85%-91%), and when the cases were
      reported from both death registry and health insurance systems (97%, 95% CI: 94%
      100%). Among the remaining cases, 87 (8.1%) had other respiratory diseases
      (chiefly pneumonia and asthma; n=85) and 71 (6.6%) cases showed no evidence of
      any respiratory disease on their clinical records. CONCLUSION: In the People's
      Republic of China, COPD diagnoses obtained from electronic health records are of
      good quality and suitable for large population-based studies and do not warrant
      systematic adjudication of all the reported cases.

PMID- 27042035
TI  - Risk stratification for COPD diagnosis through an active search strategy in
      primary care.
AB  - BACKGROUND: The aim of this study was to identify the percentage of undiagnosed
      patients with COPD through the implementation of an active search strategy in a
      selected subject population. METHODS: An observational, cross-sectional,
      multicenter study was conducted in a primary care setting in Spain. General
      practitioners gave their diagnostic impression of COPD (yes/no) on the basis of
      clinical criteria of subjects with respiratory symptoms and tobacco exposure.
      Subsequently, post-bronchodilator spirometry and quality-of-life tests were
      performed. Multivariate logistic regression techniques using receiver operating
      characteristic (ROC) curves were used to identify the combination of variables
      that best discriminates COPD. RESULTS: A total of 2,758 patients were screened at
      368 primary care centers, of which 1,725 patients were included in the study.
      Seven hundred and ninety-three patients (46%) were diagnosed with COPD. Clinical
      judgment resulted in suspected COPD in 1,393 (81%) of the subjects. The best
      variables to discriminate COPD were a history of lower respiratory tract
      infections, cough, and dyspnea. This combination identified COPD with a ROCAUC of
      0.61 denoting a poor discriminative ability. CONCLUSION: Employing an active
      search strategy leads to a new COPD diagnosis in almost half of the subjects.
      Screening of COPD with post-bronchodilator spirometry should be considered
      mandatory for any high-risk subject visiting the general practitioner clinic for
      any reason.

PMID- 27042036
TI  - Striving for optimal bronchodilation: focus on olodaterol.
AB  - beta2-agonists were introduced in the 1940s as bronchodilators to be used in
      obstructive respiratory diseases. Long-acting beta2-agonists have been a mainstay
      of bronchodilating treatment for decades. Recently, agents extending their effect
      to 24 hours and thus allowing the once-daily administration were introduced,
      defined as very-long-acting beta2-agonists. Olodaterol is a new very-long-acting
      beta2-agonist that has been shown, in controlled trials, to improve lung function
      as well as clinical outcomes and quality of life. Most of these trials included
      patients with moderate, severe, or very severe chronic obstructive pulmonary
      disease (COPD). Olodaterol has a rapid onset of action (comparable to formoterol)
      and provides bronchodilation over 24 hours. In controlled trials, olodaterol was
      shown to be as effective as formoterol twice daily, but significantly superior in
      terms of quality of life in patients with COPD. The safety profile of olodaterol
      was very good, with a rate of adverse events, including the cardiac events that
      are particularly important for beta2-agonists, comparable to placebo. Also, the
      efficiency of the Respimat((r)) device concurs to the effectiveness of treatment.

PMID- 27042038
TI  - Incidence and outcomes of patients hospitalized with COPD exacerbation with and
      without pneumonia.
AB  - BACKGROUND: Pneumonia may be a major contributor to hospitalizations for chronic
      obstructive pulmonary disease (COPD) exacerbation and influence their outcomes.
      METHODS: We examined hospitalization rates, health resource utilization, 30-day
      mortality, and risk of subsequent hospitalizations for COPD exacerbations with
      and without pneumonia in Denmark during 2006-2012. RESULTS: We identified 179,759
      hospitalizations for COPD exacerbations, including 52,520 first-time
      hospitalizations (29.2%). Pneumonia was frequent in first-time exacerbations
      (36.1%), but declined in successive exacerbations to 25.6% by the seventh or
      greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per
      1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic
      exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000
      population during the same period. A number of markers of health resource
      utilization were more prevalent in pneumonic exacerbations than in nonpneumonic
      exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission
      (7.7% vs 12.5%), and several acute procedures. Thirty-day mortality was 12.1% in
      first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic
      cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17-1.24). Pneumonia
      also predicted increased mortality associated with a second exacerbation (aHR
      1.14, 95% CI 1.11-1.18), and up to a seventh or greater exacerbation (aHR 1.10,
      95% CI 1.07-1.13). In contrast, the aHR of a subsequent exacerbation was 8%-13%
      lower for patients with pneumonic exacerbations. CONCLUSIONS: Pneumonia is
      frequent among patients hospitalized for COPD exacerbations and is associated
      with increased health care utilization and higher mortality. Nonpneumonic COPD
      exacerbations predict increased risk of subsequent exacerbations.

PMID- 27042037
TI  - Bacterial-viral load and the immune response in stable and exacerbated COPD:
      significance and therapeutic prospects.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by persistent
      airflow limitation and an abnormal inflammatory response of the lung. Bacteria
      and viruses are a major cause of COPD exacerbations and may contribute to COPD
      progression by perpetuating the inflammatory response in the airways. Bacterial
      variety diminishes with increasing COPD severity. Respiratory viruses can
      colonize the lower respiratory tract in stable COPD, altering the respiratory
      microbiome and facilitating secondary bacterial infections. In this review, we
      present the most updated information about the role of bacteria and viruses in
      stable and exacerbated COPD. In our opinion, to optimize therapeutic strategies,
      the dynamic events involving bacterial-viral infections and related immune
      response in COPD phenotypes need to be better clarified. Our paper would address
      these points that we consider of great importance for the clinical management of
      COPD. 

PMID- 27042039
TI  - COPD phenotypes on computed tomography and its correlation with selected lung
      function variables in severe patients.
AB  - BACKGROUND: Computed tomography (CT) phenotypic characterization helps in
      understanding the clinical diversity of chronic obstructive pulmonary disease
      (COPD) patients, but its clinical relevance and its relationship with functional
      features are not clarified. Volumetric capnography (VC) uses the principle of gas
      washout and analyzes the pattern of CO2 elimination as a function of expired
      volume. The main variables analyzed were end-tidal concentration of carbon
      dioxide (ETCO2), Slope of phase 2 (Slp2), and Slope of phase 3 (Slp3) of
      capnogram, the curve which represents the total amount of CO2 eliminated by the
      lungs during each breath. OBJECTIVE: To investigate, in a group of patients with
      severe COPD, if the phenotypic analysis by CT could identify different subsets of
      patients, and if there was an association of CT findings and functional
      variables. SUBJECTS AND METHODS: Sixty-five patients with COPD Gold III-IV were
      admitted for clinical evaluation, high-resolution CT, and functional evaluation
      (spirometry, 6-minute walk test [6MWT], and VC). The presence and profusion of
      tomography findings were evaluated, and later, the patients were identified as
      having emphysema (EMP) or airway disease (AWD) phenotype. EMP and AWD groups were
      compared; tomography findings scores were evaluated versus spirometric, 6MWT, and
      VC variables. RESULTS: Bronchiectasis was found in 33.8% and peribronchial
      thickening in 69.2% of the 65 patients. Structural findings of airways had no
      significant correlation with spirometric variables. Air trapping and EMP were
      strongly correlated with VC variables, but in opposite directions. There was some
      overlap between the EMP and AWD groups, but EMP patients had signicantly lower
      body mass index, worse obstruction, and shorter walked distance on 6MWT.
      Concerning VC, EMP patients had signicantly lower ETCO2, Slp2 and Slp3. Increases
      in Slp3 characterize heterogeneous involvement of the distal air spaces, as in
      AWD. CONCLUSION: Visual assessment and phenotyping of CT in COPD patients is
      feasible and may help identify functional and clinically different subsets of
      patients. VC may provide useful information about the heterogeneous involvement
      of lung structures in COPD.

PMID- 27042040
TI  - Treatment of patients with COPD and recurrent exacerbations: the role of
      infection and inflammation.
AB  - Exacerbations of COPD represent an important medical and health care problem.
      Certain susceptible patients suffer recurrent exacerbations and as a consequence
      have a poorer prognosis. The effects of bronchial infection, either acute or
      chronic, and of the inflammation characteristic of the disease itself raise the
      question of the possible role of antibiotics and anti-inflammatory agents in
      modulating the course of the disease. However, clinical guidelines base their
      recommendations on clinical trials that usually exclude more severe patients and
      patients with more comorbidities, and thus often fail to reflect the reality of
      clinicians attending more severe patients. In order to discuss aspects of
      clinical practice of relevance to pulmonologists in the treatment and prevention
      of recurrent exacerbations in patients with severe COPD, a panel discussion was
      organized involving expert pulmonologists who devote most of their professional
      activity to day hospital care. This article summarizes the scientific evidence
      currently available and the debate generated in relation to the following
      aspects: bacterial and viral infections, chronic bronchial infection and its
      treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and
      their treatment, and the role of computerized tomography as a diagnostic tool in
      patients with severe COPD and frequent exacerbations. 

PMID- 27042041
TI  - Microparticles in sputum of COPD patients: a potential biomarker of the disease?
AB  - BACKGROUND: Microparticles (MPs) are small membrane vesicles of 0.1-1 um which
      are released by cells following chemical, physical, and apoptotic stimuli. MPs
      represent more than a miniature version of the cell. Their composition and
      function depend not only on cellular origin, but also on stimuli. Chronic
      obstructive pulmonary disease (COPD) is a lung disease characterized by nearly
      irreversible lung destruction which results in airway limitation. PURPOSE: We
      investigated the presence and source of MPs in sputum of COPD patients to
      evaluate if changes in MP number and origin may reflect the pathophysiological
      conditions of disease and may serve as potential biomarkers for diagnostic and
      prognostic use. METHODS: Induced sputum samples were collected from 18 male
      subjects and liquefied with Sputasol. MPs obtained were immunolabeled for
      leukocyte (CD11a), granulocyte (CD66b), monocyte-macrophage (CD11b), platelets
      and megakaryocytic cells (CD41), endothelial cells (CD31), and red blood cells
      (CD235ab) and analyzed by cytofluorimetry. RESULTS: There was a negative
      correlation between CD31-MPs and forced expiratory volume in 1 second (R=-53,
      P<0.05) and CD66b-MP level was correlated with worse performance index of COPD
      such as the Body mass index airflow Obstruction, Dyspnea, and Exercise capacity
      (BODE); they were negatively correlated with 6-minute walking test: 0.65 and 
      0.64, respectively (P<0.05). CD235ab-MPs showed a negative correlation with body
      mass index (R=-0.86, P<0.05), while there was a positive correlation with dyspnea
      index (R=0.91, P<0.05). CONCLUSION: The main finding of this study was that MPs
      were detected in the sputum of patients affected by COPD. The phenotype of some
      of them was related to the main COPD parameters. These results suggest that MPs
      could be implicated in the pathogenesis of COPD.

PMID- 27042042
TI  - The optimum timing to wean invasive ventilation for patients with AECOPD or COPD
      with pulmonary infection.
AB  - COPD is characterized by a progressive decline in lung function and mental and
      physical comorbidities. It is a significant burden worldwide due to its growing
      prevalence, comorbidities, and mortality. Complication by bronchial-pulmonary
      infection causes 50%-90% of acute exacerbations of COPD (AECOPD), which may lead
      to the aggregation of COPD symptoms and the development of acute respiratory
      failure. Non-invasive or invasive ventilation (IV) is usually implemented to
      treat acute respiratory failure. However, ventilatory support (mainly IV) should
      be discarded as soon as possible to prevent the onset of time-dependent
      complications. To withdraw IV, an optimum timing has to be selected based on
      weaning assessment and spontaneous breathing trial or replacement of IV by non-IV
      at pulmonary infection control window. The former method is more suitable for
      patients with AECOPD without significant bronchial-pulmonary infection while the
      latter method is more suitable for patients with AECOPD with acute significant
      bronchial-pulmonary infection. 

PMID- 27042043
TI  - Cognitive status among patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: We investigated the association between cognitive impairment and chronic
      obstructive pulmonary disease (COPD), taking into account demographic and
      clinical variables evaluated during routine practice. PATIENTS AND METHODS: We
      performed a post hoc analysis of a cross-sectional study that included subjects
      with stable COPD. Sociodemographic and clinical information was recorded using
      the Body mass index, airflow Obstruction, Dyspnea and Exacerbations index and the
      Charlson comorbidity index. Cognitive performance was studied by the mini-mental
      state examination, with a score less than 27 indicating clinical impairment.
      Depressive symptoms, physical activity, and quality of life (EuroQoL-5 dimensions
      and COPD Assessment Test) were also evaluated. RESULTS: The analysis included 940
      subjects. The prevalence of cognitive impairment was 39.4%. Multivariate logistic
      regression models revealed that cognitive impairment was associated with
      educational level (odds ratio [OR] =0.096, 95% confidence interval [CI] =0.011
      0.447) and poorer quality of life measured by the EuroQoL-5 dimensions social
      tariff (OR =0.967, 95% CI =0.950-0.983). When questionnaires were not included in
      the analysis, cognitive impairment was associated with educational level (OR
      =0.063, 95% CI =0.010-0.934), number of exacerbations (OR =11.070, 95% CI =1.450
      84.534), Body mass index, airflow Obstruction, Dyspnea and Exacerbations index
      score (OR =1.261, 95% CI =1.049-1.515), and the Charlson comorbidity index (OR
      =1.412, 95% CI =1.118-1.783). CONCLUSION: Cognitive impairment is common in COPD
      and is associated with low educational level, higher disease severity, and
      increased comorbidity. This could have therapeutic implications for this
      population.

PMID- 27042044
TI  - Combining systems pharmacology, transcriptomics, proteomics, and metabolomics to
      dissect the therapeutic mechanism of Chinese herbal Bufei Jianpi formula for
      application to COPD.
AB  - Bufei Jianpi formula (BJF) has long been used as a therapeutic agent in the
      treatment of COPD. Systems pharmacology identified 145 active compounds and 175
      potential targets of BJF in a previous study. Additionally, BJF was previously
      shown to effectively prevent COPD and its comorbidities, such as ventricular
      hypertrophy, by inhibition of inflammatory cytokine production, matrix
      metalloproteinases expression, and other cytokine production, in vivo. However,
      the system-level mechanism of BJF for the treatment of COPD is still unclear. The
      aim of this study was to gain insight into its system-level mechanisms by
      integrating transcriptomics, proteomics, and metabolomics together with systems
      pharmacology datasets. Using molecular function, pathway, and network analyses,
      the genes and proteins regulated in COPD rats and BJF-treated rats could be
      mainly attributed to oxidoreductase activity, antioxidant activity, focal
      adhesion, tight junction, or adherens junction. Furthermore, a comprehensive
      analysis of systems pharmacology, transcript, protein, and metabolite datasets is
      performed. The results showed that a number of genes, proteins, metabolites
      regulated in BJF-treated rats and potential target proteins of BJF were involved
      in lipid metabolism, cell junction, oxidative stress, and inflammatory response,
      which might be the system-level therapeutic mechanism of BJF treatment. 

PMID- 27042045
TI  - Relationship of airflow limitation severity with work productivity reduction and
      sick leave in a Japanese working population.
AB  - BACKGROUND: The aim of this study was to reveal the association between airflow
      limitation (AL) severity and reduction with work productivity as well as use of
      sick leave among Japanese workers. METHODS: This cross-sectional study included
      1,378 workers who underwent a lung function test during a health checkup at the
      Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced
      expiratory volume in 1 second/forced vital capacity of <0.7. Workers completed a
      questionnaire on productivity loss at work and sick leave. The quality and
      quantity of productivity loss at work were measured on a ten-point scale
      indicating how much work was actually performed on the previous workday.
      Participants were asked how many days in the past 12 months they were unable to
      work because of health problems. Logistic regression analysis was used to assess
      the associations between AL severity and the quality and quantity of productivity
      loss at work as well as use of sick leave. RESULTS: Compared with workers without
      AL, workers with moderate-to-severe AL showed a significant productivity loss
      (quality: odds ratio [OR] =2.04, 95% confidence interval [CI]: 1.12-3.71, P=0.02
      and quantity: OR =2.19, 95% CI: 1.20-4.00, P=0.011) and use of sick leave (OR
      =2.69, 95% CI: 1.33-5.44, P=0.006) after adjusting for sex, age, body mass index,
      smoking status, hypertension, hyperglycemia, dyslipidemia, sleep duration, work
      hours per day, and workplace smoking environment. CONCLUSION: AL severity was
      significantly associated with work productivity loss and use of sick leave. Our
      findings suggested that early intervention in the subjects with AL at the
      workforce might be beneficial for promoting work ability.

PMID- 27042046
TI  - COPD exacerbation care bundle improves standard of care, length of stay, and
      readmission rates.
AB  - INTRODUCTION: COPD is the third leading cause of death in the world. Utilizing
      care bundles during acute COPD exacerbations results in fewer complications and
      lower costs. Our aim was to construct a COPD exacerbation care bundle and
      evaluate the effects on patient care. METHODS: We conducted a prospective
      analysis of 44 patients admitted with a COPD exacerbation to a single tertiary
      care facility. Primary outcomes included length of stay, readmission rates, and
      hospital costs. Secondary outcomes included patient education, pulmonologist
      follow-up, and timeliness of medication administration. Two cohorts were
      analyzed: those treated with an electronic COPD care bundle (cases; N=22) versus
      those treated without the care bundle (controls; N=22). RESULTS: Mean length of
      stay (51.2 vs 101.1 hours in controls; P-value =0.001), 30-day readmission rates
      (9.1% vs 54.4% in controls; P-value =0.001), and 60-day readmission rates (22.7%
      vs 77% in controls; P-value =0.0003) decreased in the care bundle group. Ninety
      day hospital costs had a significant difference in the care bundle group
      (US$7,652 vs US$19,954 in controls; P-value =0.044). Secondary outcomes included
      a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001),
      59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P
      value =0.005), and a mean reduction in time to steroid administration (7.0 hours;
      P-value =0.015) seen in the care bundle cases. CONCLUSION: Our significant
      findings coupled with the recent success of standardized algorithms in managing
      COPD exacerbations stress the importance of enforcing clinical guidelines that
      can enhance patient care. We demonstrated improved care for COPD exacerbation
      patients during hospitalizations, thereby decreasing morbidity and the financial
      burden hospitals face in regard to this increasingly prevalent disease.

PMID- 27042047
TI  - Physical exercise is effective in preventing cigarette smoke-induced pulmonary
      oxidative response in mice.
AB  - Reactive oxygen species (ROS) are important in the pathogenesis of pulmonary
      injury induced by cigarette smoke (CS) exposure, and physical exercise (Ex) is
      useful in combating impaired oxidative process. We verified the preventive
      effects of Ex on lung oxidative markers induced by smoking. In this study, 36
      mice (C57BL-6, 30-35 g) were split into four groups: control, CS, Ex, and CS plus
      Ex. Ex groups were given prior physical training in water (2*30 min/d, 5 days/wk,
      8 weeks). After training, the CS groups were subjected to passive exposure to
      four cigarettes, 3 * per day, for 60 consecutive days. After 24 hours from the
      last exposure, CS animals were sacrificed, and lung samples were collected for
      further analysis. Left lung sample was prepared for histological analysis, and
      right lung was used for biochemical analysis (superoxide, hydroxyproline, lipid
      peroxidation [thiobarbituric acid reactive species], protein carbonylation
      [carbonyl groups formation], superoxide dismutase [SOD], catalase [CAT], and
      glutathione peroxidase [GPx] activities). Group comparisons were evaluated by
      analysis of variance (ANOVA). Results were expressed as mean +/- standard
      deviation, with P<0.05 considered significantly different. Preventive Ex impeded
      histological changes and increased the enzymatic defense system (SOD and GPx) by
      reducing oxidative damage in lipids and proteins. This preventive effect of prior
      physical Ex alleviates damage caused by CS exposure. 

PMID- 27042048
TI  - POPE study: rationale and methodology of a study to phenotype patients with COPD
      in Central and Eastern Europe.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) constitutes a major
      health challenge in Central and Eastern European (CEE) countries. However,
      clinical phenotypes, symptom load, and treatment habits of patients with COPD in
      CEE countries remain largely unknown. This paper provides a rationale for
      phenotyping COPD and describes the methodology of a large study in CEE.
      METHODS/DESIGN: The POPE study is an international, multicenter, observational
      cross-sectional survey of patients with COPD in CEE. Participation in the study
      is offered to all consecutive outpatients with stable COPD in 84 centers across
      the CEE region if they fulfill the following criteria: age >40 years, smoking
      history >=10 pack-years, a confirmed diagnosis of COPD with postbronchodilator
      FEV1/FVC <0.7, and absence of COPD exacerbation >=4 weeks. Medical history, risk
      factors for COPD, comorbidities, lung function parameters, symptoms, and
      pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is
      registered in ClinicalTrials.gov with the identifier NCT02119494. OUTCOMES: The
      primary aim of the POPE study was to phenotype patients with COPD in a real-life
      setting within CEE countries using predefined classifications. Secondary aims of
      the study included analysis of differences in symptoms, and diagnostic and
      therapeutic behavior in participating CEE countries. CONCLUSION: There is
      increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The
      POPE study may contribute to reveal important information regarding phenotypes
      and therapy in real-life CEE.

PMID- 27042049
TI  - Erratum: The Short Physical Performance Battery is a discriminative tool for
      identifying patients with COPD at risk of disability [Corrigendum].

PMID- 27042050
TI  - COPD in primary lung cancer patients: prevalence and mortality.
AB  - BACKGROUND: Previous studies have relied on international spirometry criteria to
      diagnose COPD in patients with lung cancer without considering the effect lung
      cancer might have on spirometric results. The aim of this study was to examine
      the prevalence of COPD and emphysema at the time of primary lung cancer diagnosis
      and to examine factors associated with survival. MATERIALS AND METHODS: Medical
      records, pulmonary function tests, and computed tomography scans were used to
      determine the presence of COPD and emphysema in patients diagnosed with primary
      lung cancer at the University Hospital of North Norway in 2008-2010. RESULTS:
      Among the 174 lung cancer patients, 69% had COPD or emphysema (39% with COPD, 59%
      with emphysema; male:female ratio 101:73). Neither COPD nor emphysema were
      significantly associated with lung cancer mortality, whereas patients with non
      small-cell lung cancer other than adenocarcinoma and squamous cell carcinoma had
      a risk of lung cancer mortality that was more than four times higher than that of
      patients with small-cell lung cancer (hazard ratio [HR] 4.19, 95% confidence
      interval [CI] 1.56-11.25). Females had a lower risk of lung cancer mortality than
      males (HR 0.63, 95% CI 0.42-0.94), and patients aged >=75 years had a risk that
      was twice that of patients aged <75 years (HR 2.48, 95% CI 1.59-3.87). Low
      partial arterial oxygen pressure (4.0-8.4 kPa) increased the risk of lung cancer
      mortality (HR 2.26, 95% CI 1.29-3.96). So did low partial arterial carbon dioxide
      pressure (3.0-4.9 kPa) among stage IV lung cancer patients (HR 2.23, 95% CI 1.29
      3.85). Several patients with respiratory failure had previously been diagnosed
      with COPD. CONCLUSION: The observed prevalence of COPD was lower than that in
      previous studies. Neither COPD nor emphysema were significantly associated with
      lung cancer mortality.

PMID- 27042051
TI  - Three-dimensional culture and interaction of cancer cells and dendritic cells in
      an electrospun nano-submicron hybrid fibrous scaffold.
AB  - An artificial three-dimensional (3D) culture system that mimics the tumor
      microenvironment in vitro is an essential tool for investigating the cross-talk
      between immune and cancer cells in tumors. In this study, we developed a 3D
      culture system using an electrospun poly(epsilon-caprolactone) (PCL) nanofibrous
      scaffold (NFS). A hybrid NFS containing an uninterrupted network of nano- and
      submicron-scale fibers (400 nm to 2 um) was generated by deposition onto a
      stainless steel mesh instead of an aluminum plate. The hybrid NFS contained
      multiplanar pores in a 3D structure. Surface-seeded mouse CT26 colon cancer cells
      and bone marrow-derived dendritic cells (BM-DCs) were able to infiltrate the
      hybrid NFS within several hours. BM-DCs cultured on PCL nanofibers showed a
      baseline inactive form, and lipopolysaccharide (LPS)-activated BM-DCs showed
      increased expression of CD86 and major histocompatibility complex Class II. Actin
      and phosphorylated FAK were enriched where unstimulated and LPS-stimulated BM-DCs
      contacted the fibers in the 3D hybrid NFS. When BM-DCs were cocultured with
      mitoxantrone-treated CT26 cells in a 3D hybrid NFS, BM-DCs sprouted cytoplasm to,
      migrated to, synapsed with, and engulfed mitoxantrone-treated CT26 cancer cells,
      which were similar to the naturally occurring cross-talk between these two types
      of cells. The 3D hybrid NFS developed here provides a 3D structure for coculture
      of cancer and immune cells. 

PMID- 27042052
TI  - Design of a novel theranostic nanomedicine: synthesis and physicochemical
      properties of a biocompatible polyphosphazene-platinum(II) conjugate.
AB  - To develop a theranostic nanomedicine involving the antitumor-active moiety
      (dach)Pt(II) (dach: trans-(+/-)-1,2-diaminocyclohexane) of oxaliplatin (OX), a
      new biocompatible polyphosphazene carrier polymer was designed by grafting with a
      methoxy poly(ethylene glycol) (MPEG) to increase duration of circulation in the
      blood and with aminoethanol (AE) as a spacer group. The antitumor (dach)Pt moiety
      was conjugated to the carrier polymer using cis-aconitic acid (AA) as a linker,
      resulting in a polymer conjugate formulated as [NP(MPEG550)(AE-AA)Pt(dach)]n,
      named "Polyplatin" (PP). PP was found to self-assemble into very stable polymeric
      nanoparticles with a mean diameter of 55.1 nm and a critical aggregation
      concentration of 18.5 mg/L in saline. PP could easily be labeled with a
      fluorescence dye such as Cy5.5 for imaging studies. The time-dependent ex vivo
      image studies on organ distributions and clearance of Cy-labeled PP have shown
      that PP accumulated in the tumor with high selectivity by the enhanced
      permeability and retention effect but was cleared out from all the major organs
      including the liver in about 4 weeks postinjection. Another time-dependent
      bioimaging study on distribution and clearance of PP in mouse kidney using laser
      ablation inductively coupled plasma mass spectroscopy has shown that PP
      accumulates much less in kidney and is more rapidly excreted than monomeric OX,
      which is in accord with the very low acute toxicity of PP as shown by its high
      LD50 value of more than 2000 mg/kg. The pharmacokinetic study of PP has shown
      that it has a much longer half-life (t 1/2beta) of 13.3 hours compared with the
      5.21 hours of OX and about a 20 times higher area under the curve value of
      42,850.8 ng h/mL compared with the 2,320.4 ng h/mL of OX. The nude mouse
      xenograft trials of PP against the gastric MKN-28 tumor cell line exhibited
      remarkably better tumor efficacy compared with OX at the higher tolerated dose,
      with lower systemic toxicity.

PMID- 27042053
TI  - Liquid crystal nanoparticle formulation as an oral drug delivery system for liver
      specific distribution.
AB  - Liquid crystal nanoparticles have been utilized as an efficient tool for drug
      delivery with enhanced bioavailability, drug stability, and targeted drug
      delivery. However, the high energy requirements and the high cost of the liquid
      crystal preparation have been obstacles to their widespread use in the
      pharmaceutical industry. In this study, we prepared liquid crystal nanoparticles
      using a phase-inversion temperature method, which is a uniquely low energy
      process. Particles prepared with the above method were estimated to be ~100 nm in
      size and exhibited a lamellar liquid crystal structure with orthorhombic lateral
      packing. Pharmacokinetic and tissue distribution studies of a hydrophobic peptide
      based drug candidate formulated with the liquid crystal nanoparticles showed a
      five-fold enhancement of bioavailability, sustained release, and liver-specific
      drug delivery compared to a host-guest complex formulation. 

PMID- 27042054
TI  - Insights into the therapeutic potential of hypoxia-inducible factor-1alpha small
      interfering RNA in malignant melanoma delivered via folate-decorated cationic
      liposomes.
AB  - Malignant melanoma (MM) represents the most dangerous form of skin cancer, and
      its incidence is expected to rise in the coming time. However, therapy for MM is
      limited by low topical drug concentration and multidrug resistance. This article
      aimed to develop folate-decorated cationic liposomes (fc-LPs) for hypoxia
      inducible factor-1alpha (HIF-1alpha) small interfering (siRNA) delivery, and to
      evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1alpha
      siRNA-loaded fc-LPs (siRNA-fc-LPs) were prepared by a film hydration method
      followed by siRNA incubation. Folate decoration of liposomes was achieved by
      incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA
      fc-LPs were 95.3 nm in size with a zeta potential of 2.41 mV. The liposomal
      vectors exhibited excellent loading capacity and protective effect toward siRNA.
      The in vitro cell transfection efficiency was almost parallel to the commercially
      available LipofectamineTM 2000. Moreover, the anti-melanoma activity of HIF
      1alpha siRNA was significantly enhanced through fc-LPs. Western blot analysis and
      apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the
      production of HIF-1alpha-associated protein and induced the apoptosis of hypoxia
      tolerant melanoma cells. Our designed liposomal vectors might be applicable as
      siRNA delivery vehicle to systemically or topically treat MM. 

PMID- 27042055
TI  - In vivo osseointegration of Ti implants with a strontium-containing nanotubular
      coating.
AB  - Novel biomedical titanium (Ti) implants with high osteogenic ability for fast and
      good osseointegration under normal as well as osteoporotic conditions are
      urgently needed. Expanding on our previous in vitro results, we hypothesized that
      nanotubular, strontium-loaded (NT-Sr) structures on Ti implants would have
      favorable osteogenic effects and evaluated the in vivo osseointegration of these
      implants in rats. The structures with nanotubes of different diameters were
      fabricated by electrochemical anodization at 10 and 40 V, and the amounts of Sr
      loaded were adjusted by using two hydrothermal treatment times of 1 and 3 hours.
      Qualitative microcomputed tomography in two and three dimensions showed that the
      NT-Sr formed with an anodization voltage of 10 V and hydrothermal treatment time
      of 3 hours best supported bone growth in vivo. Histomorphometric examination of
      osseointegration also showed that more newly formed bone was found at its
      surface. The bone-implant contact percentage was highest (92.48%+/-0.76%) at 12
      weeks. In conclusion, the NT-Sr formed with an anodization voltage of 10 V and
      hydrothermal treatment time of 3 hours showed excellent osteogenic properties,
      making it an attractive option for Ti surface modification with considerable
      clinical potential. 

PMID- 27042057
TI  - Photothermal treatment of liver cancer with albumin-conjugated gold nanoparticles
      initiates Golgi Apparatus-ER dysfunction and caspase-3 apoptotic pathway
      activation by selective targeting of Gp60 receptor [Corrigendum].

PMID- 27042056
TI  - Spermine-modified Antheraea pernyi silk fibroin as a gene delivery carrier.
AB  - The development of a novel cationized polymer used as a gene delivery carrier
      that can conveniently and effectively transfect cells resulting in a stably
      expressed target gene remains a challenge. Antheraea pernyi silk fibroin (ASF) is
      a cytocompatible and biodegradable natural polymer, and it possesses Arg-Gly-Asp
      sequences but a negative charge. In order to render ASF amenable to packaging
      plasmid DNA (pDNA), spermine was used to modify ASF to synthesize cationized ASF
      (CASF), which was used as a gene delivery carrier. CASF was characterized using
      trinitrobenzene sulfonic acid assay, the zeta potential determination, and a
      Fourier transform infrared analysis, and the results of these characterizations
      indicated that the -NH2 in spermine effectively reacts with the -COOH in the side
      chains of ASF. Spermine grafted to the side chains of ASF resulted in the
      conversion of the negative charge of ASF to a positive charge. CASF packaged pDNA
      and formed CASF/pDNA complexes, which exhibited spherical morphology with average
      particle sizes of 215-281 nm and zeta potential of approximately +3.0 mV to +3.2
      mV. The results of the MTT assay, confocal laser scanning microscopy, and flow
      cytometry analysis in a human endothelial cell line revealed that CASF/pDNA
      complexes exhibited lower cytotoxicity and higher transfection efficiency
      compared to the pDNA complexes of polyethyleneimine. These results indicate that
      our synthesized CASF, a cationized polymer, is a potential gene delivery carrier
      with the advantages of biodegradability and low cytotoxicity. 

PMID- 27042058
TI  - Colloidal nanocarriers for the enhanced cutaneous delivery of naftifine:
      characterization studies and in vitro and in vivo evaluations.
AB  - In topical administration of antifungals, the drugs should pass the stratum
      corneum to reach lower layers of the skin in effective concentrations. Thus, the
      formulation of antifungal agents into a suitable delivery system is important for
      the topical treatment of fungal infections. Nanosized colloidal carriers have
      gained great interest during the recent years to serve as efficient promoters of
      drug penetration into the skin. Microemulsions are soft colloidal nanosized drug
      carriers, which are thermodynamically stable and isotropic systems. They have
      been extensively explored for the enhancement of skin delivery of drugs. This
      study was carried out to exploit the feasibility of colloidal carriers as to
      improve skin transport of naftifine, which is an allylamine antifungal drug. The
      microemulsions were formulated by construction of pseudoternary phase diagrams
      and composed of oleic acid (oil phase), Kolliphor((r)) EL or Kolliphor((r)) RH40
      (surfactant), Transcutol((r)) (cosurfactant), and water (aqueous phase). The
      plain and drug-loaded microemulsions were characterized in terms of isotropy,
      particle size and size distribution, pH value, refractive index, viscosity, and
      conductivity. The in vitro skin uptake of naftifine from microemulsions was
      studied using tape stripping technique in pig skin. The drug penetrated
      significantly into stratum corneum from microemulsions compared to its marketed
      cream (P<0.05). Moreover, the microemulsion formulations led to highly
      significant amount of naftifine deposition in deeper layers of skin than that of
      commercial formulation (P<0.001). Microemulsion-skin interaction was confirmed by
      attenuated total reflectance - Fourier transformed infrared spectroscopy data, in
      vitro. The results of the in vivo tape stripping experiment showed similar trends
      as the in vitro skin penetration study. Topical application of the microemulsion
      on human forearms in vivo enhanced significantly the distribution and the amount
      of naftifine penetrated into the stratum corneum as compared to the marketed
      formulation (P<0.05). The relative safety of the microemulsion formulations was
      demonstrated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      viability test. This study indicated that the nanosized colloidal carriers
      developed could be considered as an effective and safe topical delivery system
      for naftifine.

PMID- 27042059
TI  - Study of the combined treatment of lung cancer using gene-loaded immunomagnetic
      albumin nanospheres in vitro and in vivo.
AB  - Combination therapy for lung cancer has garnered widespread attention. Radiation
      therapy, gene therapy, and molecular targeted therapy for lung cancer have
      certain effects, but the disadvantages of these treatment methods are evident.
      Combining these methods can decrease their side effects and increase their
      curative effects. In this study, we constructed a pYr-ads-8-5HRE-cfosp-iNOS-IFNG
      plasmid (a gene circuit that can express IFNgamma), which is a gene circuit, and
      used that plasmid together with C225 (cetuximab) to prepare gene-loaded
      immunomagnetic albumin nanospheres (IMANS). Moreover, we investigated the
      therapeutic effects of gene-loaded IMANS in combination with radiation therapy on
      human lung cancer in vitro and in vivo. The results showed that this gene circuit
      was successively constructed and confirmed that the expression of INFgamma was
      increased due to the gene circuit. Gene-loaded IMANS combined with radiation
      therapy demonstrated improved results in vitro and in vivo. In conclusion, gene
      loaded IMANS enhanced the efficacy of combination therapy, solved problems
      related to gene transfer, and specifically targeted lung cancer cells.

PMID- 27042060
TI  - One-step self-assembled nanomicelles for improving the oral bioavailability of
      nimodipine.
AB  - Our study aimed to develop a self-assembled nanomicelle for oral administration
      of nimodipine (NIM) with poor water solubility. Using Solutol((r)) HS15, the NIM
      loaded self-assembled nanomicelles displayed a near-spherical morphology with a
      narrow size distribution of 12.57 +/- 0.21 nm (polydispersity index =0.071 +/-
      0.011). Compared with Nimotop((r)) (NIM tablets), the intestinal absorption of
      NIM from NIM nanomicelle in rats was improved by 3.13- and 2.25-fold in duodenum
      and jejunum at 1 hour after oral administration. The cellular transport of NIM
      nanomicelle in Caco-2 cell monolayers was significantly enhanced compared to that
      of Nimotop((r)). Regarding the transport pathways, clathrin, lipid raft/caveolae,
      and macropinocytosis mediated the cell uptake of NIM nanomicelles, while P
      glycoprotein and endoplasmic reticulum/Golgi complex (ER/Golgi) pathways were
      involved in exocytosis. Pharmacokinetic studies in our research laboratory have
      showed that the area under the plasma concentration-time curve (AUC0-infinity) of
      NIM nanomicelles was 3.72-fold that of Nimotop((r)) via oral administration in
      rats. Moreover, the NIM concentration in the brain from NIM nanomicelles was
      dramatically improved. Therefore, Solutol((r)) HS15-based self-assembled
      nanomicelles represent a promising delivery system to enhance the oral
      bioavailability of NIM.

PMID- 27042061
TI  - Aminoclay-lipid hybrid composite as a novel drug carrier of fenofibrate for the
      enhancement of drug release and oral absorption.
AB  - This study aimed to prepare the aminoclay-lipid hybrid composite to enhance the
      drug release and improve the oral bioavailability of poorly water-soluble
      fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying
      method was adopted to incorporate fenofibrate into aminoclay-lipid hybrid
      composite (ALC). The optimal composition of the ALC formulation was determined as
      the ratios of aminoclay to krill oil of 3:1 (w/w), krill oil to fenofibrate of
      2:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The morphological
      characteristics of ALC formulation were determined using scanning electron
      microscopy, differential scanning calorimetry, and X-ray powder diffraction,
      which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC
      formulation achieved almost complete dissolution within 30 minutes, whereas the
      untreated powder and physical mixture exhibited less than 15% drug release.
      Furthermore, ALC formulation effectively increased the peak plasma concentration
      (C max) and area under the curve (AUC) of fenofibric acid (an active metabolite)
      in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC
      formulation exhibited much lower moisture sorption behavior than the lyophilized
      formulation using sucrose as a cryoprotectant. Taken together, the present
      findings suggest that ALC formulation is promising for improving the oral
      absorption of poorly soluble fenofibrate. 

PMID- 27042062
TI  - Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy.
AB  - A mixture of docetaxel (DTX) and Solutol((r)) HS 15 (Solutol) transiently formed
      nanodroplets when it was suspended in an aqueous medium. However, nanodroplets
      that comprised DTX and Solutol showed a rapid precipitation of DTX because of
      their unstable characteristics in the aqueous medium. The incorporation of
      nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent
      stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX
      loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of
      DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets
      (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to
      156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX
      by vesicle fusion and multilayered structure, respectively. Also, a long
      circulation of the multilayer NPs was observed, and this was due to the presence
      of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved
      antitumor efficacy based on the enhanced permeation and retention effect.
      Therefore, this study indicated that the multilayer NPs have a considerable
      potential as a drug delivery system with an enhanced therapeutic efficacy by
      blood circulation and with low side effects. 

PMID- 27042063
TI  - Destruction of vasculogenic mimicry channels by targeting epirubicin plus
      celecoxib liposomes in treatment of brain glioma.
AB  - The efficacy of chemotherapy for brain glioma is restricted by the blood-brain
      barrier (BBB), and surgery or radiotherapy cannot eliminate the glioma cells
      because of their unique location. Residual brain glioma cells can form
      vasculogenic mimicry (VM) channels that can cause a recurrence of brain glioma.
      In the present study, targeting liposomes incorporating epirubicin and celecoxib
      were prepared and used for the treatment of brain glioma, along with the
      destruction of their VM channels. Evaluations were performed on the human brain
      glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice.
      Targeting epirubicin plus celecoxib liposomes in the circulatory blood system
      were able to be transported across the BBB, and accumulated in the brain glioma
      region. Then, the liposomes were internalized by brain glioma cells and killed
      glioma cells by direct cytotoxic injury and the induction of apoptosis. The
      induction of apoptosis was related to the activation of caspase-8- and -3
      signaling pathways, the activation of the proapoptotic protein Bax, and the
      suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma
      VM channels was related to the downregulation of VM channel-forming indictors,
      which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated
      that the targeting epirubicin plus celecoxib liposomes were able to effectively
      destroy the glioma VM channels and exhibited significant efficacy in the
      treatment of intracranial glioma-bearing nude mice. Therefore, targeting
      epirubicin plus celecoxib liposomes could be a potential nanostructured
      formulation to treat gliomas and destroy their VM channels. 

PMID- 27042064
TI  - Sustained dual release of placental growth factor-2 and bone morphogenic protein
      2 from heparin-based nanocomplexes for direct osteogenesis.
AB  - OBJECTIVE: To compare the direct osteogenic effect between placental growth
      factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). METHODS: Three groups
      of PlGF-2/BMP-2-loaded heparin-N-(2-hydroxyl) propyl-3-trimethyl ammonium
      chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 MUg PlGF-2;
      with 1.0 MUg BMP-2; and with 0.5 MUg PlGF-2 combined with 1.0 MUg BMP-2. The
      loading efficiencies and release profiles of these growth factors (GFs) in this
      nanocomplex system were quantified using enzyme-linked immunosorbent assay, their
      biological activities were evaluated using cell counting kit-8, cell morphology,
      and cell number counting assays, and their osteogenic activities were quantified
      using alkaline phosphatase and Alizarin Red S staining assays. RESULTS: The
      loading efficiencies were more than 99% for the nanocomplexes loaded with just
      PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex
      loaded with just BMP-2, the loading efficiency was more than 97%. About 83%-84%
      of PlGF-2 and 89%-91% of BMP-2 were stably retained on the nanocomplexes for at
      least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects
      comparable to those of BMP-2 despite its dose in the experiments being lower than
      that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes
      encapsulating two GFs have enhanced potential in the enhancement of osteoblast
      function. CONCLUSION: PlGF-2-loaded heparin-HTCC nanocomplexes may constitute a
      promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and
      BMP-2 appears to have greater potential in bone tissue regeneration than the
      delivery of either GFs alone.

PMID- 27042065
TI  - The efficiency of magnetic hyperthermia and in vivo histocompatibility for human
      like collagen protein-coated magnetic nanoparticles.
AB  - Magnetic hyperthermia is a promising technique for the minimally invasive
      elimination of solid tumors. In this study, uniform magnetite nanoparticles
      (MNPs) with different particle sizes were used as a model system to investigate
      the size and surface effects of human-like collagen protein-coated MNPs (HLC
      MNPs) on specific absorption rate and biocompatibility. It was found that these
      HLC-MNPs possess rapid heating capacity upon alternating magnetic field exposure
      compared to that of MNPs without HLC coating, irrespective of the size of MNPs.
      The significant enhancement of specific absorption rate is favorable for larger
      sized nanoparticles. Such behavior is attributed to the reduced aggregation and
      increased stability of the HLC-MNPs. By coating HLC on the surface of certain
      sized MNPs, a significant increase in cell viability (up to 2.5-fold) can be
      achieved. After subcutaneous injection of HLC-MNPs into the back of Kunming mice,
      it was observed that the inflammatory reaction hardly occurred in the injection
      site. However, there was a significant presence of phagocytes and endocytosis
      after the injection of nonconjugated counterparts. The overall strategy to
      fabricate HLC-MNPs can serve as a general guideline to address the current
      challenges in clinical magnetic hyperthermia, improved biocompatibility, and
      enhanced heating characteristics through protein coating.

PMID- 27042066
TI  - The preparation of metal-organic frameworks and their biomedical application.
AB  - The development of a safe and targetable drug carrier is a major challenge. An
      efficient delivery system should protect cargo from degradation and cleanup, and
      control of drug release in the target site. Metal-organic frameworks (MOFs),
      consisting of metal ions and a variety of organic ligands, have been applied for
      drug delivery due to their distinct structure. In this review, we summarized the
      synthesis strategies of MOFs, especially emphasizing the methods of pore creation
      in frameworks, which were based on recent literatures. Subsequently, the
      controlled size, biocompatibility, drug releasing performances, and imaging of
      MOFs were discussed, which would pave the road for the application in drug
      delivery systems. 

PMID- 27042067
TI  - An Internet-based program for depression using activity and physiological
      sensors: efficacy, expectations, satisfaction, and ease of use.
AB  - PURPOSE: Computerized cognitive behavioral therapy (CCBT) has been shown to be
      efficacious. Moreover, CCBT can be enhanced by using physiological and activity
      sensors, but there is no evidence about the acceptability of all these tools. The
      objective of this study is to examine the efficacy, expectations, satisfaction,
      and ease of use of an Internet-based CCBT program for preventing depression, with
      and without sensors (electroencephalography, electrocardiograhpy ECG, and
      actigraphy), in a high-risk population (unemployed men). PATIENTS AND METHODS:
      Sixty participants at risk of depression (unemployed men) were randomly assigned
      to three experimental conditions: 1) intervention program (N=22), 2) intervention
      program plus sensors (N=19), and 3) control group (N=19). Participants completed
      depression, anxiety, positive and negative affect, and perceived stress measures.
      Furthermore, they also completed the measures for expectation, satisfaction, and
      the ease of use of the program. RESULTS: Results showed that the two intervention
      groups improved significantly more than the control group on the clinical
      variables, and the improvements were greater in the group that used sensors than
      in the group that did not use them. Furthermore, participants in both
      intervention groups scored high on expectations and satisfaction with the CCBT
      program (with and without sensors). The mean score for usability was 88 out of
      100 (standard deviation =12.32). No significant differences were found between
      groups on any of these variables. CONCLUSION: This is the first study to analyze
      the efficacy, expectations, satisfaction, and ease of use of an Internet-based
      program using physiological and activity sensors. These results suggest that an
      Internet program for depression with or without physiological and activity
      sensors is effective, satisfactory, and easy to use.

PMID- 27042068
TI  - The noradrenergic paradox: implications in the management of depression and
      anxiety.
AB  - Both major depressive disorder and the anxiety disorders are major causes of
      disability and markedly contribute to a significant global burden of the disease
      worldwide. In part because of the significant socioeconomic burden associated
      with these disorders, theories have been developed to specifically build clinical
      treatment approaches. One such theory, the monoaminergic hypothesis, has led to
      the development of several generations of selective and nonselective inhibitors
      of transporters of serotonin and norepinephrine, with the goal of augmenting
      monoaminergic transmission. These efforts have led to considerable success in the
      development of antidepressant therapeutics. However, there is a strong
      correlation between enhanced noradrenergic activity and fear and anxiety.
      Consequently, some physicians have expressed concerns that the same enhanced
      noradrenergic activity that alleviates depression could also promote anxiety. The
      fact that the serotonergic and noradrenergic reuptake inhibitors are successfully
      used in the treatment of anxiety and panic disorders seems paradoxical. This
      review was undertaken to determine if any clinical evidence exists to show that
      serotonergic and noradrenergic reuptake inhibitors can cause anxiety. The PubMed,
      EMBASE, and Cochrane Library databases were searched, and the results limited to
      randomized, double-blind, placebo-controlled studies performed in nongeriatric
      adults and with clear outcome measures were reported. Based on these criteria, a
      total of 52 studies were examined. Patients in these studies suffered from
      depression or anxiety disorders (generalized and social anxiety disorders, panic
      disorder, and posttraumatic stress disorder). The large majority of these studies
      employed venlafaxine or duloxetine, and the remainder used tri-cyclic
      antidepressants, atomoxetine, or reboxetine. All the studies reported clinically
      significant alleviation of depressive and/or anxious symptoms by these
      therapeutics. In none of these studies was anxiety a treatment-emergent adverse
      effect. This review argues against the impression that enhanced generalized
      noradrenergic activity promotes the emergence of anxiety. 

PMID- 27042069
TI  - Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly
      patients with cognitive impairment: an efficacy-tolerability pilot study.
AB  - OBJECTIVE: This pilot study evaluated the efficacy and safety of prolonged
      release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild
      to-moderate cognitive impairment. METHODS: This was a prospective, observational,
      open-label study of 45-day duration. Patients with moderate-to-severe chronic
      pain and naive to strong opioids were recruited from nursing homes and
      Alzheimer's disease centers. OXN-PR was initiated at low doses (5 mg od or bid)
      and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain
      intensity reduction of >=30% from baseline (T0) to 15 days after OXN-PR
      initiation, as assessed by a numerical rating scale or the Pain Assessment in
      Advanced Dementia scale. Other assessments included the Barthel activities of
      daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse
      events. RESULTS: The analysis included 53 patients (mean age, 83.0 years; mean
      Mini-Mental State Examination score, 18.6) with severe pain (median Numerical
      Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment
      in daily functioning (mean Barthel index, 32.2). The primary endpoint was
      achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity
      from baseline to study end (numerical rating scale, 6.6+/-1.0 vs 2.3+/-1.1,
      P<0.0001; Pain Assessment in Advanced Dementia, 6.9+/-1.6 vs 0.9+/-0.8,
      P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean
      Barthel index, 32.2+/-16.8 vs 53.7+/-23.9, P<0.0001) and neuropsychiatric
      symptoms (mean Neuropsychiatric Inventory, 25.5+/-27.3 vs 8.8+/-9.0, P<0.0001)
      were also reported. OXN-PR was well tolerated and did not worsen bowel function.
      CONCLUSION: In this pilot study, OXN-PR was effective in improving pain and other
      symptoms associated with dementia, with a favorable safety and tolerability
      profile. Large-scale trials in people with dementia are needed to improve
      clinical guidance for the assessment and treatment of pain in these fragile
      individuals.

PMID- 27042070
TI  - Attention deficit hyperactivity disorder and disordered eating behaviors: links,
      risks, and challenges faced.
AB  - Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      that often persists in adulthood. It is defined by inattention and/or
      hyperactivity-impulsivity. ADHD is associated with many comorbidities, including
      eating disorders (EDs). In the last decade, studies have reported that ADHD is
      linked with binge EDs, bulimia nervosa, and anorexia nervosa. Many postulates
      have been proposed to explain the association: 1) impulsive behavior in ADHD
      patients leads to disordered eating behavior; 2) other psychologic comorbidities
      present in ADHD patients account for eating behavior; 3) poor eating habits and
      resulting nutritional deficiencies contribute to ADHD symptoms; and 4) other risk
      factors common to both ADHD and EDs contribute to the coincidence of both
      diseases. Additionally, sex differences become a significant issue in the
      discussion of EDs and ADHD because of the higher incidence of bulimia nervosa and
      anorexia nervosa in females and the ability of females to mask the symptoms of
      ADHD. Interestingly, both EDs and ADHD rely on a common neural substrate, namely,
      dopaminergic signaling. Dopaminergic signaling is critical for motor activity and
      emotion, the latter enabling the former into a combined motivated movement like
      eating. This linkage aids in explaining the many comorbidities associated with
      ADHD. The interconnection of ADHD and EDs is discussed from both a historical
      perspective and the one based on the revealing nature of its comorbidities. 

PMID- 27042071
TI  - Occurrence of ADHD in parents of ADHD children in a clinical sample.
AB  - BACKGROUND: Despite the fact that there is a large amount of research on
      childhood attention deficit hyperactivity disorder (ADHD) treatment and an
      increasing amount of research on adult ADHD, little is known about the prevalence
      and influence of parental ADHD. Therefore, this study examined the frequency of
      parental ADHD in a clinical sample of German children suffering from ADHD. We
      also tried to find different levels of symptom severity for prognostic relevance.
      Furthermore, the association between subtypes of ADHD in children and their
      parents was investigated. METHOD: In this study, parents of 79 ADHD children were
      screened for ADHD according to the Diagnostic and Statistical Manual of Mental
      Disorders, 5th edition and International Classification of Diseases, 10th
      edition. The Wender Utah Rating Scale and the ADHS-Self-Report were given to 75
      mothers and 49 fathers for retrospective and current symptoms. Frequency of ADHD
      symptoms and severity groups was calculated and relationship between parental and
      children's ADHD was tested. RESULTS: ADHD occurrence for mothers of children with
      ADHD was 41.3%, for fathers 51.0%. About 16.0% of the mothers had a mixed type,
      9.3% had a hyperactive-impulsive subtype, and 16.0% had an inattentive subtype.
      Of the fathers, 18.4% had a mixed type, 10.2% had a hyperactive-impulsive
      subtype, and 22.4% had an inattentive subtype; 61% of the mothers and 46.9% of
      the fathers had low symptom severity. Medium symptom severity was reported by
      37.7% mothers and 46.9% fathers, while 1.3% of the mothers and 6.2% of the
      fathers showed severe symptoms. No significant correlation between parental and
      child diagnoses was observed. CONCLUSION: As nearly half of the parents suffered
      from ADHD, these results are a matter of concern in families with ADHD children.
      Besides parent-child interactions, parental ADHD symptoms might influence
      parental education style and also effects parent training as well as the child's
      therapy outcome. In the future, parents should be screened for ADHD symptoms if
      they or their child receive treatment and to adjust processes and design of
      treatment to the symptoms.

PMID- 27042072
TI  - No association between BDNF Val66Met polymorphism and treatment response in
      obsessive-compulsive disorder in the Japanese population.
AB  - AIM: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin
      family, and it promotes the development and function of dopaminergic and
      serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is
      associated with a decrease in activity-dependent secretion of BDNF compared with
      the Val allele, and a number of studies have provided evidence for the
      association between this polymorphism and obsessive-compulsive disorder (OCD).
      The purpose of this study was to investigate whether this functional variant of
      the BDNF gene is associated with OCD and treatment response in patients with OCD
      in the Japanese population. METHODS: We first performed a case-control
      association study between the BDNF Val66Met polymorphism and OCD (175 cases and
      2,027 controls). Then, we examined an association between this polymorphism and
      treatment response in 96 patients with OCD. RESULTS: We found no significant
      association between the Met allele and OCD risk or between the Met allele and
      treatment responses to selective serotonin reuptake inhibitors or serotonin
      reuptake inhibitor with an atypical antipsychotic (P>0.05). CONCLUSION: Our
      results suggest that the BDNF Val66Met polymorphism may not be associated as a
      risk factor for developing OCD or with therapeutic response in patients with OCD
      in the Japanese population.

PMID- 27042073
TI  - Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in
      mouse brains.
AB  - The past decade has resulted in an increase in the knowledge of molecular
      mechanisms underlying brain injury induced by intracerebral hemorrhage (ICH).
      Recent advances have provided a link between epigenetic modification and the
      regulation of gene expression. 5-hydroxymethylcytosine (5hmC) converted from 5
      methylcytosine by the ten-eleven translocation (TET) family of proteins has
      emerged as a new epigenetic modification. While the dynamics of 5hmC during
      cerebral ischemia have recently been reported, whether 5hmC is involved in ICH
      remains unexplored. In this study, we investigated the effects of ICH on DNA
      hydroxymethylation. We showed that the global level of 5hmC rapidly decreased as
      early as 24 hours after ICH and persisted until 72 hours. Furthermore, the level
      of 5hmC in the CpG-rich regions of Akt2, Pdpk1 and Vegf genes was significantly
      decreased with a minimum level observed at 48 hours or 72 hours. Decreased 5hmC
      was observed in parallel with an increase in 5-methylcytosine over this time
      course, and mRNA levels of Akt2, Pdpk1 and Vegf were downregulated upon ICH
      injury. Finally, Tet1, Tet2 and Tet3 mRNA levels were dramatically decreased in
      the ICH brain. Our study for the first time established the correlation between
      DNA hydroxymethylation and ICH injury. Further investigations should examine
      whether 5hmC modification could be a therapeutic target for the treatment of ICH
      injury. 

PMID- 27042074
TI  - Cognitive behavioral therapy in pharmacoresistant obsessive-compulsive disorder.
AB  - BACKGROUND: The aim of the study was to determine whether patients with obsessive
      compulsive disorder (OCD) resistant to drug therapy may improve their condition
      using intensive, systematic cognitive behavioral therapy (CBT) lasting for 6
      weeks, and whether it is possible to predict the therapeutic effect using
      demographic, clinical, and selected psychological characteristics at baseline.
      METHODS: Sixty-six OCD patients were included in the study, of which 57 completed
      the program. The diagnosis was confirmed using the structured Mini International
      Neuropsychiatric Interview. Patients were rated using the objective and
      subjective forms of the Yale-Brown Obsessive Compulsive Scale, objective and
      subjective forms of the Clinical Global Impression, Beck Anxiety Inventory, Beck
      Depression Inventory, Dissociative Experiences Scale, 20-item Somatoform
      Dissociation Questionnaire, and the Sheehan Disability Scale before their
      treatment, and with subjective Yale-Brown Obsessive Compulsive Scale, objective
      and subjective Clinical Global Impression, Beck Anxiety Inventory, and Beck
      Depression Inventory at the end of the treatment. Patients were treated with
      antidepressants and daily intensive group CBT for the 6-week period. RESULTS:
      During the 6-week intensive CBT program in combination with pharmacotherapy,
      there was a significant improvement in patients suffering from OCD resistant to
      drug treatment. There were statistically significantly decrease in the scores
      assessing the severity of OCD symptoms, anxiety, and depressive feelings. A lower
      treatment effect was achieved specifically in patients who 1) showed fewer OCD
      themes in symptomatology, 2) showed a higher level of somatoform dissociation, 3)
      had poor insight, and 4) had a higher initial level of overall severity of the
      disorder. Remission of the disorder was more likely in patients who had 1) good
      insight, 2) a lower initial level of anxiety, and 3) no comorbid depressive
      disorder.

PMID- 27042075
TI  - Yokukansan improves behavioral and psychological symptoms of dementia by
      suppressing dopaminergic function.
AB  - Although three drugs, risperidone, yokukansan, and fluvoxamine, have shown equal
      efficacy in treating behavioral and psychological symptoms of dementia (BPSD) in
      our previous study, their mechanisms of action are different from one another.
      Monoamines have attracted attention for their key roles in mediating several
      behavioral symptoms or psychological symptoms through synaptic signaling. We
      aimed to clarify the monoamines changed by treatment with each drug in patients
      with BPSD. The main purpose of this study was to determine whether plasma levels
      of catecholamine metabolites are correlated with pharmacological treatments. This
      was an 8-week, rater-blinded, randomized, flexible-dose, triple-group trial. In
      total, 90 subjects were recruited and subsequently three different drugs were
      allocated to 82 inpatients with BPSD. We examined BPSD data from patients who
      completed 8 weeks of treatment. Eventually, we analyzed 42 patients (yokukansan:
      17; risperidone: 9; fluvoxamine: 16). Homovanillic acid, a metabolite of
      dopamine, and 3-methoxy-4-hydroxyphenylglycol, a metabolite of noradrenaline, in
      their plasma were analyzed by high-performance liquid chromatography with
      electrochemical detection. All three drugs showed equal significant efficacy
      between baseline and study endpoint. By contrast, biomarkers showed mutually
      different changes. Patients in the yokukansan group had significantly decreased
      plasma homovanillic acid levels from baseline. Conversely, patients in the
      risperidone and fluvoxamine groups exhibited no significant changes in plasma
      homovanillic acid levels from baseline. Yokukansan contains geissoschizine methyl
      ether, which is known to have a partial agonist effect on dopamine D2 receptors.
      An improvement in BPSD condition with the intake of yokukansan is suggested to
      occur through a suppressed dopaminergic function, which is similar to the effect
      of aripiprazole. 

PMID- 27042076
TI  - One patient with Sjogren's syndrome presenting schizophrenia-like symptoms.
AB  - Comorbid depression in patients with Sjogren's syndrome has been reported
      frequently, while comorbid psychosis in subjects with Sjogren's syndrome has
      rarely been reported. Here we report a patient with Sjogren's syndrome who
      presented with schizophrenia-like symptoms such as persecutory delusions and
      auditory hallucinations in contrast to her previous psychiatric presentations,
      which only included depression and anxiety. 

PMID- 27042077
TI  - Quality of life and parental styles assessed by adolescents suffering from
      inflammatory bowel diseases and their parents.
AB  - BACKGROUND: Inflammatory bowel diseases (IBDs) in adolescents are chronic medical
      conditions with a substantial influence on the quality of life (QoL) of the
      families. METHODS: A total of 27 adolescents suffering from IBD, 39 healthy
      adolescents, and their parents were included in the cross-sectional study. The
      adolescents completed the questionnaires ADOR (parenting styles), KidScreen-10
      (QoL), SAD (The Scale of Anxiety in Children), and CDI (Children's Depression
      Inventory). The parents completed the BAI (Beck Anxiety Inventory), BDI-II (Beck
      Depression Inventory, second version), and PedsQL (Pediatrics Quality of Life)
      Family Impact Module. RESULTS: The parental styles of the parents of the IBD
      adolescents and controls were without significant differences. The only exception
      was that fathers' positive parental style was significantly higher in the fathers
      of the controls. There were no statistically significant differences between the
      IBD children and controls in the QoL assessed using KidScreen-10. However, the
      QoL of the parents of the ill children was significantly lower than that of the
      parents of the controls (PedsQL total scores in mothers 66.84+/-14.78 vs 76.17+/
      14.65 and in fathers 68.86+/-16.35 vs 81.74+/-12.89, respectively). The mothers
      of the IBD adolescents were significantly more anxious (BAI scores 9.50+/-10.38
      vs 5.26+/-4.75) and the fathers more depressed (BDI-II scores 7.23+/-6.50 vs
      3.64+/-3.51) than the parents of the controls, but there was no difference in the
      levels of anxiety or depression between the IBD adolescents and the controls. The
      positive parental style of both the parents of the children suffering from IBD
      positively correlated with the QoL of the adolescents evaluated by KidScreen-10.
      The positive parental style of the fathers negatively correlated with the
      children's state and trait anxiety and negatively correlated with the severity of
      childhood depression. CONCLUSION: The fathers of the IBD adolescents may exhibit
      low levels of positive parenting style and be mildly depressed, and the mothers
      tend to exhibit higher levels of anxiety.

PMID- 27042078
TI  - TotalTrack video intubating laryngeal mask in super-obese patients - series of
      cases.
AB  - BACKGROUND: Super-obese patients are at increased risk of difficult mask
      ventilation and difficult intubation. Therefore, devices that allow for
      simultaneous ventilation/oxygenation during attempts to visualize the entrance to
      the larynx, increase patient safety. TotalTrack video intubating laryngeal mask
      is a new device that allows for ventilation during intubation efforts. PATIENTS
      AND METHODS: Twenty-four super-obese patients (body mass index >50 kg/m(2)) were
      divided into two subgroups: intubation efforts using 1) TotalTrack and 2)
      Macintosh blade standard laryngoscope in induction of general anesthesia.
      Visualization and successful intubation was evaluated for both groups with
      ventilation and post-mask complications additionally evaluated for TotalTrack.
      RESULTS: In all cases in the TotalTrack group, the Cormack-Lehane score was 1,
      ventilation and intubation was successful in 11/12 patients. No hypoxia during
      intubation efforts was recorded. No serious complications of use of TotalTrack
      were observed. In the Macintosh blade laryngoscope group, all patients were
      intubated, but the Cormack-Lehane score was 2 in four cases, and 3 in three
      cases. CONCLUSION: TotalTrack video intubating laryngeal mask is a device that
      allows for better visualization of the larynx compared to the standard Macintosh
      blade laryngoscope, it provides effective ventilation/oxygenation and intubation
      in super-obese patients.

PMID- 27042080
TI  - The use of oral suspension and rationally prescribing alternatives may be
      supplemental to the implementation of clopidogrel new algorithm comprising
      CYP2C19 pharmacogenetics and drug interactions.

PMID- 27042079
TI  - Dimethyl fumarate in the management of multiple sclerosis: appropriate patient
      selection and special considerations.
AB  - Delayed-release dimethyl fumarate (DMF), also known as gastroresistant DMF, is
      the most recently approved oral disease-modifying treatment (DMT) for relapsing
      multiple sclerosis. Two randomized clinical trials (Determination of the Efficacy
      and Safety of Oral Fumarate in Relapsing-Remitting MS [DEFINE] and Comparator and
      an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis [CONFIRM])
      demonstrated significant efficacy in reducing relapse rate and radiological signs
      of disease activity, as seen on magnetic resonance imaging. The DEFINE study also
      indicated a significant effect of DMF on disability worsening, while the low
      incidence of confirmed disability worsening in the CONFIRM trial rendered an
      insignificant reduction among the DMF-treated groups when compared to placebo.
      DMF also demonstrated a good safety profile and acceptable tolerability, since
      the most common side effects (gastrointestinal events and flushing reactions) are
      usually transient and mild to moderate in severity. Here, we discuss the place in
      therapy of DMF for individuals with relapsing multiple sclerosis, providing a
      tentative therapeutic algorithm to manage newly diagnosed patients and those who
      do not adequately respond to self-injectable DMTs. Literature data supporting the
      potential role of DMF as a first-line therapy are presented. The possibility of
      using DMF as switching treatment or even as an add-on strategy in patients with
      breakthrough disease despite self-injectable DMTs will also be discussed. Lastly,
      we argue about the role of DMF as an exit strategy from natalizumab-treated
      patients who are considered at risk for developing multifocal progressive
      leukoencephalopathy. 

PMID- 27042081
TI  - Reduction in total recurrent cardiovascular events in acute coronary syndrome
      patients with low-density lipoprotein cholesterol goal <70 mg/dL: a real-life
      cohort in a developing country.
AB  - BACKGROUND: For investigations into cardiovascular disease, the first problematic
      event (ie, nonfatal acute coronary syndrome (ACS), nonfatal stroke, or all-cause
      mortality) generally was considered as the primary end point; however, ACS
      patients often experience subsequent events, which are rarely considered. This
      study reports an investigation into whether achieving a low-density lipoprotein
      cholesterol (LDL-C) goal of <70 mg/dL (1.8 mmol/L) is associated with a reduction
      in total recurrent cardiovascular events in a cohort of ACS patients hospitalized
      in northern Thailand. METHODS: The medical charts and the electronic hospital
      database of ACS patients treated with statins at a tertiary hospital in Thailand
      between 2009 and 2012 were reviewed. Patients were checked for their LDL-C goal
      attainment, and then were followed for subsequent events until the last follow-up
      date, or to December 31, 2012. The Wei-Lin-Weissfeld method was used for multiple
      time-to-events data to investigate the association between achieving an LDL-C
      goal of <70 mg/dL and total recurrent cardiovascular events. RESULTS: Of 405
      eligible patients, 110 patients attained an LDL-C goal of <70 mg/dL. During a
      median follow-up of 1.94 years, the majority of patients (88.6%) had no
      subsequent cardiovascular events, while 46 patients experienced at least one
      recurrent cardiovascular event: 36 with one event, six with two events, two with
      three events, one with four events, and one with seven events. Compared to
      patients with an LDL-C >=100 mg/dL, patients achieving an LDL-C of <70 mg/dL were
      significantly less likely to experience total cardiovascular events (adjusted
      hazard ratio =0.29; 95% confidence interval =0.09-0.87; P-value =0.028); the
      result was similar to patients with an LDL-C of 70-100 mg/dL, but it was not
      significant (adjusted hazard ratio =0.53; 95% confidence interval =0.23-1.26; P
      value =0.154). CONCLUSION: ACS patients receiving statins who attained an LDL-C
      <70 mg/dL experienced a reduction in total recurrent cardiovascular events
      compared to those with LDL-C >=100 mg/dL.

PMID- 27042082
TI  - Methylnaltrexone for opioid-induced constipation: review and meta-analyses for
      objective plus subjective efficacy and safety outcomes.
AB  - INTRODUCTION: Opioid-induced constipation (OIC) is a frequent adverse event that
      impairs patients' quality of life. This article evaluates the objective plus
      subjective efficacy and the safety of methylnaltrexone (MNTX) in OIC patients.
      METHODS: Randomized controlled trials from a recent systematic review were
      included. In addition, a PubMed search was conducted for January 2014 to December
      21, 2015. We included randomized controlled trials with adult OIC patients, MNTX
      as study drug, and OIC as primary outcome. Results were categorized in three
      outcome types: objective outcome measures (eg, time to laxation), patient
      reported outcomes (eg, straining), and global burden measures (eg, constipation
      distress). Dichotomous meta-analyses with risk ratios (RRs) and 95% confidence
      intervals (CIs) were calculated using RevMan 5.3. Only comparisons between MNTX
      and placebo were made. RESULTS: We included seven studies with 1,860 patients. A
      meta-analysis revealed that patients under MNTX had considerably more rescue-free
      bowel movement within 4 hours after the first dose (RR 3.74, 95% CI 2.87 to 4.86;
      five studies, n=938; I (2)=0). Results of the review indicated that patients
      under MNTX had a higher stool frequency and needed less time to laxation compared
      with placebo. Moreover, patients receiving MNTX tended to have better values in
      patient-reported outcomes and global burden measures. Meta-analyses on safety
      revealed that patients under MNTX experienced more abdominal pain (RR 2.38, 95%
      CI 1.75 to 3.23; six studies, n=1,412; I (2)=60%) but showed a nonsignificant
      tendency in nausea (RR 1.27, 95% CI 0.90 to 1.78; six studies, n=1,412; I
      (2)=12%) and diarrhea (RR 1.45, 95% CI 0.94 to 2.24; five studies, n=1,258; I
      (2)=45%). The incidence of MNTX-related serious adverse events was 0.2%
      (4/1,860). CONCLUSION: MNTX has been shown to be effective and safe. Future
      randomized controlled trials should consequently incorporate objective outcome
      measures, patient-reported outcomes, and global burden measures, and research the
      efficacy of MNTX in other populations, for example, patients under opioids after
      surgical procedures.

PMID- 27042083
TI  - Antibiotic prescribing and resistance: knowledge level of medical students of
      clinical years of University Sultan Zainal Abidin, Malaysia.
AB  - The innovation of penicillin by Dr Alexander Fleming in 1928 and its use in
      clinical practice saved many lives, especially during the Second World War.
      Tuberculosis still carries a significant public health threat and has re-emerged
      over the past two decades, even in modern countries where tuberculosis was
      thought to be eliminated. The World Health Organization defines antimicrobial
      resistance as the resistance of a microorganism to an antimicrobial drug that was
      initially effective for treatment of infections caused by the microbe. Therefore,
      the findings of the current study will provide data to enable the design of a new
      educational program to better equip our students in confronting antimicrobial
      resistance. This study was a cross-sectional, questionnaire-based survey, which
      was undertaken in the Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala
      Terengganu, Malaysia. The study participants were students of the Bachelor of
      Medicine and Bachelor of Surgery program (MBBS) of Year III, IV, and V. A total
      of 142 out of 164 (86%) medical students returned the questionnaire.
      Specifically, the year-wise breakdown of responses was 29% (41), 39% (55), and
      32% (45) for Year III, IV, and V, respectively. Among the study respondents, 28%
      (40) were male, and the remaining 72% (102) were female. In all, 67% of the
      participants felt more confident in "making an accurate diagnosis of
      infection/sepsis." The majority (88%) of the study participants stated that they
      would like more training on antibiotic selection. This research has found that
      there is a gap between theoretical input and clinical practice; the students are
      demanding more educational intervention to face the threat of antimicrobial
      resistance. 

PMID- 27042084
TI  - Prevalence of diabetes and determinants: evidence from a minority region in
      People's Republic of China.
AB  - BACKGROUND: This study aimed to examine the prevalence of diabetes mellitus and
      other categories of glucose intolerance (impaired glucose tolerance and impaired
      fasting glucose) and explore the risk factors in an ethnic minority region,
      Guangxi Zhuang Autonomous Region, People's Republic of China. METHODS: A
      population-based study enrolled 53,270 residents older than 5 years in Guangxi,
      People's Republic of China. The prevalence of diabetes was calculated using the
      1999 World Health Organization (WHO) oral glucose tolerance test diagnostic
      criteria. RESULTS: Among 53,270 individuals, the prevalence of diabetes, impaired
      glucose tolerance, and impaired fasting glucose was 5.96%, 7.36%, and 2.62%,
      respectively. Of the 3,173 individuals with diabetes mellitus, 696 (21.94%) were
      found to have a history of diabetes and 2,477 (78.06%) were newly diagnosed. A
      lower prevalence was found in Zhuang ethnic minority people compared with the
      majority of Han people. The prevalence was significantly associated with age,
      body mass index, waist-to-hip ratio, dyslipidemia, medical history of
      hypertension, and family history of diabetes. CONCLUSION: Guangxi shows a rapidly
      rising prevalence of diabetes. Weight control and blood lipid control are
      important to decrease the rapidly increasing prevalence of diabetes in Guangxi,
      an ethnic minority region.

PMID- 27042085
TI  - The effect of sitagliptin on cardiovascular risk profile in Korean patients with
      type 2 diabetes mellitus: a retrospective cohort study.
AB  - BACKGROUND: A 2013 postmarketing study suggested a possible link between
      saxagliptin use and hospital admission for heart failure. Cardiovascular (CV)
      effects of sitagliptin, the most commonly prescribed antidiabetic in the same
      class as saxagliptin, have not been evaluated much in Asian patients with type 2
      diabetes. This study sought to ascertain the CV safety of sitagliptin in Korean
      patients. METHODS: A retrospective cohort study of 4,860 patients who were
      classified into the sitagliptin and metformin groups was conducted using
      electronic patient data retrieved from a major tertiary care medical center in
      Korea. Primary composite end points included CV death, myocardial infarction, and
      ischemic stroke. Secondary composite end points included the aforementioned
      individual primary outcomes plus hospitalization due to unstable angina, heart
      failure, or coronary revascularization. A Cox proportional-hazards model was used
      to compare CV risk associated with drug exposure. RESULTS: Following propensity
      score (PS) matching in a 1:2 ratio, 1,620 patients in the sitagliptin group and
      3,240 patients in the metformin group were identified for cohort entry. The PS
      matched hazard ratio (HR) and 95% confidence interval (CI) for sitagliptin
      relative to metformin were, respectively, 0.831 and 0.536-1.289 (P=0.408) for
      primary end point and 1.140 and 0.958-1.356 (P=0.139) for secondary end point.
      Heart failure hospitalization rates did not differ significantly between the two
      groups, with the PS-matched HR of 0.762 and 95% CI of 0.389-1.495 (P=0.430). When
      only those patients at high risk of ischemic heart disease were included for
      analysis, no excess CV risk was observed with sitagliptin compared with
      metformin. Overall, there were no substantial between-group differences in rates
      of adverse events, such as hypoglycemia and incident pancreatic disease.
      CONCLUSION: Sitagliptin was not associated with elevated risk of CV complications
      including myocardial infarction, ischemic stroke, heart failure, and coronary
      revascularization, compared to metformin therapy among Korean patients with type
      2 diabetes.

PMID- 27042086
TI  - Development and novel therapeutics in hepatocellular carcinoma: a review.
AB  - This review summarizes the epidemiological trend, risk factors, prevention
      strategies such as vaccination, staging, current novel therapeutics, including
      the drugs under clinical trials, and future therapeutic trends for hepatocellular
      carcinoma (HCC). As HCC is the third most common cause of cancer-related death
      worldwide, its overall incidence remains alarmingly high in the developing world
      and is steadily rising across most of the developed and developing world. Over
      the past 15 years, the incidence of HCC has more than doubled and it increases
      with advancing age. Chronic infection with hepatitis B virus is the leading cause
      of HCC, closely followed by infection with hepatitis C virus. Other factors
      contributing to the development of HCC include alcohol abuse, tobacco smoking,
      and metabolic syndrome (including obesity, diabetes, and fatty liver disease).
      Treatment options have improved in the past few years, particularly with the
      approval of several molecular-targeted therapies. The researchers are actively
      pursuing novel therapeutic targets as well as predictive biomarker for treatment
      of HCC. Advances are being made in understanding the mechanisms underlying HCC,
      which in turn could lead to novel therapeutics. Nevertheless, there are many
      emerging agents still under clinical trials and yet to show promising results.
      Hence, future therapeutic options may include different combination of novel
      therapeutic interventions. 

PMID- 27042087
TI  - Type II endoleaks: challenges and solutions.
AB  - Type II endoleaks are the most common endovascular complications of endovascular
      abdominal aortic aneurysm repair (EVAR); however, there has been a divided
      opinion regarding their significance in EVAR. Some advocate a conservative
      approach unless there is clear evidence of sac expansion, while others maintain
      early intervention is best to prevent adverse late outcomes such as rupture.
      There is a lack of level-one evidence in this challenging group of patients, and
      due to a low event rate of complications, large numbers of patients would be
      required in well-designed trials to fully understand the natural history of type
      II endoleak. This review will discuss the imaging, management, and outcome of
      patients with isolated type II endoleaks following infra-renal EVAR.

PMID- 27042088
TI  - A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer.
AB  - Patients with breast cancer along with metastatic estrogen and progesterone
      receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative
      tumors are referred to as having metastatic triple-negative breast cancer (mTNBC)
      disease. Although there have been many new treatment options approved by the Food
      and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic
      breast cancer, relatively few new agents have been approved for patients with
      mTNBC. There have been several head-to-head chemotherapy trials performed within
      the metastatic setting, and much of what is applied in clinical practice is
      extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and
      anthracyclines incorporated early on in the patient's treatment course. Select
      synergistic combinations can produce faster and more significant response rates
      compared with monotherapy and are typically used in the setting of visceral
      threat or symptomatic disease. Preclinical studies have implicated other possible
      targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing
      new chemotherapeutic strategies and agents, including targeted therapy and
      immunotherapy. In this review, we evaluate the standard systemic and future
      treatment options in mTNBC. 

PMID- 27042089
TI  - Fluorine-19 MRI Contrast Agents for Cell Tracking and Lung Imaging.
AB  - Fluorine-19 ((19)F)-based contrast agents for magnetic resonance imaging stand to
      revolutionize imaging-based research and clinical trials in several fields of
      medical intervention. First, their use in characterizing in vivo cell behavior
      may help bring cellular therapy closer to clinical acceptance. Second, their use
      in lung imaging provides novel noninvasive interrogation of the ventilated
      airspaces without the need for complicated, hard-to-distribute hardware. This
      article reviews the current state of (19)F-based cell tracking and lung imaging
      using magnetic resonance imaging and describes the link between the methods
      across these fields and how they may mutually benefit from solutions to mutual
      problems encountered when imaging (19)F-containing compounds, as well as hardware
      and software advancements. 

PMID- 27042091
TI  - Kissing Bug (Triatoma spp.) Intrusion into Homes: Troublesome Bites and
      Domiciliation.
AB  - Kissing bugs (Triatoma spp.) frequently enter homes and bite human and pet
      occupants. Bites may lead to severe allergic reactions and, in some cases, death.
      Kissing bugs are also vectors of Trypanosoma cruzi, the cause of Chagas disease.
      In general, modern houses in the United States are not conducive to domiciliation
      of kissing bugs (bugs living out their entire life within the home with the
      presence of eggs, nymphs, adults, and exuviae). Construction features such as
      concrete foundations, solid walls and ceilings, window screens, tight thresholds
      for doors and windows, and other measures impede bug entry into homes, and air
      conditioning reduces the need for open doors and windows. Where Chagas disease is
      endemic in Mexico and Central and South America, homes often have thatch roofs,
      adobe walls, and open doors and windows. We investigated numerous instances of
      kissing bug intrusions into homes in Southern Arizona, California, and Louisiana
      and documented the reactions to kissing bug bites. Our work confirms the
      importance of modern home construction in limiting kissing bug intrusions. Older
      homes, especially those lacking modern screening, caulking, and weather stripping
      to reduce air leakage, may be subject to kissing bug intrusions and
      domiciliation. We describe a community in Southern Arizona where domiciliation of
      homes by Triatoma recurva is common. We also provide recent data regarding
      kissing bug bites and allergic reactions to the bites. 

PMID- 27042092
TI  - Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil
      and Gas Extraction and Processing Emissions.
AB  - Carbon disulfide (CS2) has been historically associated with the manufacturing of
      rayon, cellophane, and carbon tetrachloride production. This study is one of the
      first to identify elevated atmospheric levels of CS2 above national background
      levels and its mechanisms to dysregulate normal glucose metabolism. Interference
      in glucose metabolism can indirectly cause other complications (diabetes,
      neurodegenerative disease, and retinopathy), which may be preventable if proper
      precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds
      present in the atmosphere in residential areas where unconventional shale oil and
      gas extraction and processing operations were occurring. Ambient atmospheric
      concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103
      ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric
      concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental
      Protection Agency Urban Air Toxic Monitoring Program study as a baseline
      comparison for atmospheric CS2 concentrations found in this study, it was
      determined that CS2 atmospheric levels were consistently elevated in areas where
      unconventional oil and gas extraction and processing occurred. The mechanisms by
      which CS2 interferes in normal glucose metabolism by dysregulation of the
      tryptophan metabolism pathway are presented in this study. The literature review
      found an increased potential for alteration of normal glucose metabolism in
      viscose rayon occupational workers exposed to CS2. Occupational workers in the
      energy extraction industry exposed to CS2 and other sulfide compounds may have an
      increased potential for glucose metabolism interference, which has been an
      indicator for diabetogenic effect and other related health impacts. The
      recommendation of this study is for implementation of regular monitoring of blood
      glucose levels in CS2-exposed populations as a preventative health measure. 

PMID- 27042093
TI  - Daily Fluoride Intake from Iranian Green Tea: Evaluation of Various Flavorings on
      Fluoride Release.
AB  - With increased awareness of the health benefits of the compounds in green tea,
      especially polyphenols, its consumption is rising. The main purpose of this study
      is to determine the effect of different additives on the released fluoride into
      tea liquor and also daily fluoride intake. The concentrations of fluoride,
      nitrate, sulfate, and chloride were measured in 15 different flavored green teas
      (Refah-Lahijan). The fluoride and other anion concentrations were measured by ion
      chromatography method. The data were analyzed with Statistical Package for the
      Social Sciences version 16.0. The results showed that the minimum and maximum
      concentrations of fluoride in the green tea infusions were 0.162 mg/L (cinnamon
      flavored green tea) and 3.29 mg/L (bagged peach-flavored green tea),
      respectively. The mean concentration of fluoride in the green tea leaves was 52
      mg/kg, and approximately 89% of the fluoride was released from the green tea
      leaves into the infusions after brewing. The fluoride concentrations varied
      significantly among the examined green teas (P < 0.05). However, the additives
      had no significant effect on the fluoride release into the infusions (P > 0.05).
      Finally, drinking of the studied green teas cannot make a significant
      contribution to the daily dietary intake of F for consumers. 

PMID- 27042090
TI  - Protein Modifications as Manifestations of Hyperglycemic Glucotoxicity in
      Diabetes and Its Complications.
AB  - Diabetes and its complications are hyperglycemic toxicity diseases. Many
      metabolic pathways in this array of diseases become aberrant, which is
      accompanied with a variety of posttranslational protein modifications that in
      turn reflect diabetic glucotoxicity. In this review, we summarize some of the
      most widely studied protein modifications in diabetes and its complications.
      These modifications include glycation, carbonylation, nitration, cysteine S
      nitrosylation, acetylation, sumoylation, ADP-ribosylation, O-GlcNAcylation, and
      succination. All these posttranslational modifications can be significantly
      attributed to oxidative stress and/or carbon stress induced by diabetic redox
      imbalance that is driven by activation of pathways, such as the polyol pathway
      and the ADP-ribosylation pathway. Exploring the nature of these modifications
      should facilitate our understanding of the pathological mechanisms of diabetes
      and its associated complications. 

PMID- 27042094
TI  - MicroRNAs Circulate in the Hemolymph of Drosophila and Accumulate Relative to
      Tissue microRNAs in an Age-Dependent Manner.
AB  - In mammals, extracellular miRNAs circulate in biofluids as stable entities that
      are secreted by normal and diseased tissues, and can enter cells and regulate
      gene expression. Drosophila melanogaster is a proven system for the study of
      human diseases. They have an open circulatory system in which hemolymph (HL)
      circulates in direct contact with all internal organs, in a manner analogous to
      vertebrate blood plasma. Here, we show using deep sequencing that Drosophila HL
      contains RNase-resistant circulating miRNAs (HL-miRNAs). Limited subsets of body
      tissue miRNAs (BT-miRNAs) accumulated in HL, suggesting that they may be
      specifically released from cells or particularly stable in HL. Alternatively,
      they might arise from specific cells, such as hemocytes, that are in intimate
      contact with HL. Young and old flies accumulated unique populations of HL-miRNAs,
      suggesting that their accumulation is responsive to the physiological status of
      the fly. These HL-miRNAs in flies may function similar to the miRNAs circulating
      in mammalian biofluids. The discovery of these HL-miRNAs will provide a new venue
      for health and disease-related research in Drosophila. 

PMID- 27042095
TI  - Analyses of prognostic factors in cases of non-small cell lung cancer with
      multiple brain metastases.
AB  - AIM: To observe the therapeutic efficacy and prognostic factors that influence
      survival rates in non-small cell lung cancer (NSCLC) patients with multiple brain
      metastases (BMs), (more than three and less than ten). METHODS: Retrospective
      analyses were conducted on the clinical data of 209 NSCLC patients with multiple
      BMs and were admitted to our hospital between March 2007 and November 2012. All
      BM patients received whole-brain radiotherapy. Two hundred patients received
      combined chemotherapy during the treatment process; 99 received targeted drug
      therapy; and nine got only symptomatic and supportive treatment. Survival time
      was defined as the period from the start of BM therapy to the patient's death or
      end of the follow-up period. The Kaplan-Meier method was used to calculate the
      median survival time, and the 6-month, 1-, and 2-year cumulative survival rates,
      as well as to plot the survival curves. The patients' cultural background
      included their socioeconomic status, level of education, their understanding of
      the disease, and the degree of care and support they received from their family
      members. Log-rank test was employed to test the differences in the survival rates
      between the subgroups. Cox multivariate regression analyses were used to analyze
      the various factors influencing the prognoses of NSCLC with multiple BMs.
      RESULTS: The follow-up duration was between 1 and 87 months. The median survival
      time for all BM patients was 12.1 months (95% confidence interval 9.37-14.83).
      The 6-month, 1-, and 2-year cumulative survival rates were 80%, 50.2%, and 10.7%,
      respectively. Univariate analyses revealed that the independent factors
      influencing survival prognoses included Karnofsky Performance Status score,
      control of the primary lung tumor, interval between the confirmed diagnoses of
      lung cancer and BM, presence of extracranial metastasis, number of chemotherapy
      cycles undergone, Graded Prognostic Assessment class, administration of combined
      targeted drug therapy, the pathological type, and the cultural backgrounds of the
      patients. Multivariate analyses indicated that the number of chemotherapy cycles,
      administration of combined drug therapy, and patients' cultural background were
      key independent factors influencing survival prognoses. CONCLUSION: Active
      treatment of NSCLC with multiple BMs was beneficial, and the patients' cultural
      background had a strong influence on survival prognoses. Chemotherapy combined
      with targeted drug therapy could increase the patients' median and overall
      survival rates. The number of chemotherapy cycles undergone, administration of
      combined targeted drug therapy, and the cultural backgrounds of the patients had
      significant effects on the patients' survival prognoses.

PMID- 27042096
TI  - Polymorphisms of vitamin D receptor gene TaqI susceptibility of prostate cancer:
      a meta-analysis.
AB  - OBJECTIVE: Many studies have investigated the association of the vitamin D
      receptor gene TaqI polymorphism with prostate cancer (PCa) risk. However, the
      evidence is inadequate to draw robust conclusions. To shed light on these
      inconclusive findings, we conducted a meta-analysis. MATERIALS AND METHODS: We
      searched PubMed for eligible articles. The relevant data were abstracted by two
      independent reviewers with the Stata 11.0 software. RESULTS: A total of 27
      studies were included. The pooled outcomes indicated that the TaqI genetic
      polymorphisms were significantly associated with the risk of PCa (T vs t allele:
      odds ratio [OR] =1.11, 95% confidence interval [CI] =1.03-1.21, P=0.008; TT vs
      tt: OR =1.19, 95% CI =1.01-1.42, P=0.040; TT + Tt vs tt: OR =1.18, 95% CI =1.02
      1.38, P=0.031), especially in the Asian population (T vs t allele: OR =1.11, 95%
      CI =1.03-1.21, P=0.008; TT/Tt vs tt: OR =1.93, 95% CI =1.02-3.66, P=0.043). In
      the tumor stage stratified analyses, the pooled results showed no significant
      difference in genetic polymorphisms between the local tumor group and the control
      group or between the local tumor group and the advanced tumor group. However, the
      genotypes TT and TT/Tt were significantly higher in the advanced PCa group
      compared to the control group (T vs t allele: OR =1.20, 95% CI =1.01-1.42,
      P=0.040; TT vs tt: OR =1.34, 95% CI =1.08-1.67, P=0.009; TT/Tt vs tt: OR =1.28,
      95% CI =1.05-1.56, P=0.015). CONCLUSION: The vitamin D receptor gene TaqI allele
      polymorphism might be associated with a PCa risk, especially in Asians, which
      might provide new clues for the pathogenesis research and clinical diagnosis of
      PCa in the future.

PMID- 27042098
TI  - Feasibility, tolerability, and efficacy of the concurrent addition of erlotinib
      to thoracic radiotherapy in locally advanced unresectable non-small-cell lung
      cancer: a Phase II trial.
AB  - PURPOSE: Although many studies have confirmed the synergic effects of combining
      chemotherapy (CT) and radiotherapy (RT), clinical data evaluating safety and
      efficacy of erlotinib in combination with RT in locally advanced non-small-cell
      lung cancer (NSCLC) are limited. The aim of this study was to determine the
      feasibility, tolerability, and efficacy of the concurrent addition of erlotinib
      to the standard three-dimensional conformal thoracic RT in patients with
      unresectable or locally advanced NSCLC who are not candidates for receiving
      standard CT. PATIENTS AND METHODS: Feasibility and tolerability, assessed by
      evaluating adverse events (AEs), and effectiveness, by calculating progression
      free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and
      objective response rate (ORR), were analyzed in 30 patients receiving RT alone
      and 60 receiving RT and erlotinib. RESULTS: Erlotinib with RT showed an extended
      CSS and a higher rate of complete responses compared with RT alone. No
      differences between groups were found regarding OS, PFS, and ORR. AEs were
      significantly higher in the combined treatment, which mainly included cutaneous
      toxicity, dyspnea, fatigue, hyporexia, diarrhea, and infection. Erlotinib did not
      increase the toxicity produced by RT. CONCLUSION: The combination of erlotinib
      with RT produced, in our study, a scarce clinical benefit in the treatment of
      unresectable or locally advanced NSCLC, limited to complete responses and longer
      CSS rate compared with RT alone. Increased toxicity events were associated with
      combined therapy, which mainly included cutaneous toxicity. In our opinion,
      further studies in molecularly unselected lung cancer patients treated with EGFR
      TKIs and RT are not indicated. The use of biomarkers for the identification of
      patients that are most likely to benefit from this treatment is an essential next
      step in the research of this condition.

PMID- 27042097
TI  - Myeloid cell signatures in tumor microenvironment predicts therapeutic response
      in cancer.
AB  - Tumor microenvironment (TME) consists of several immune and nonimmune cell
      populations including tumor cells. For many decades, experimental studies have
      depicted profound contribution of TME toward cancer progression and metastasis
      development. Several therapeutic strategies have been tested against TME through
      preclinical studies and clinical trials. Unfortunately, most of them have shown
      transient effect, and have largely failed due to aggressive tumor growth and
      without improving survival. Solid tumors are known to have a strong myeloid
      component (eg, tumor-associated macrophages) in tumor development. Recent data
      suggest that therapeutic responses in tumor are characterized by alterations in
      immune cell signatures, including tumor-associated myeloid cells. Polarized tumor
      associated myeloid cells (M1-M2) are critical in impairing therapeutic effect and
      promoting tumor growth. The present review is intended to compile all the
      literatures related to the emerging contribution of different populations of
      myeloid cells in the development of tumor and therapeutic failures. Finally, we
      have discussed targeting of myeloid cell populations as a combination therapy
      with chemo-, targeted-, or radiation therapies. 

PMID- 27042099
TI  - SPAG9 is involved in hepatocarcinoma cell migration and invasion via modulation
      of ELK1 expression.
AB  - BACKGROUND: Sperm-associated antigen 9 (SPAG9) is upregulated in several
      malignancies and its overexpression is positively correlated with cancer cell
      malignancies. However, the specific biological roles of SPAG9 in hepatocellular
      carcinoma (HCC) are less understood. METHODS: We analyzed SPAG9 and ETS-like gene
      1, tyrosine kinase (ELK1) expression in 50 paired HCC specimens and adjacent
      noncancerous liver specimens using immunohistochemistry. SPAG9 small interfering
      RNA (siRNA) was used to knockdown SPAG9 expression in HCCLM3 and HuH7 cell lines.
      We used plasmids to upregulate ELK1 expression and siRNA to downregulate ELK1
      expression in HuH7 cells. Quantitative real-time polymerase chain reaction and
      Western blot were used to evaluate the expression of SPAG9 and ELK1 at the mRNA
      and protein level, respectively. Wound healing, matrigel migration, and invasion
      analyses were performed to determine the effect of SPAG9 and ELK1 on HCC
      metastasis. RESULTS: SPAG9 and ELK1 were overexpressed in HCC tissue specimens
      and their expressions were higher in HCCLM3 and HuH7 cells compared to the low
      metastatic HepG2 cells. Overexpression of SPAG9 was positively associated with
      tumor-node-metastasis staging (P=0.032), metastasis parameters (P=0.018) of HCC
      patients, and ELK1 expression (r=0.422, P<0.001) in HCC tissue specimens. In
      addition, knockdown of SPAG9 in HCCLM3 and HuH7 cells using siRNA significantly
      suppressed cell migration and invasion. Furthermore, we observed inhibition of
      ELK1 expression and p38 signaling. However, ELK1 overexpression reversed the
      inhibitory effects of SPAG9 siRNA on HCC cell metastasis and ELK1 depletion
      inhibited HuH7 cell migration and invasion. CONCLUSION: SPAG9 overexpression was
      positively correlated with HCC metastasis and SPAG9-induced migration and
      invasion were partially dependent on ELK1 expression in HCC cell lines. These
      results suggest that SPAG9 may be a potential anti-metastasis target effective in
      HCC therapy.

PMID- 27042100
TI  - Clinical utility of letrozole in the treatment of breast cancer: a Chinese
      perspective.
AB  - The incidence rate of breast cancers in People's Republic of China has increased
      in the last decade, and many cases are responsive to hormone therapies. The third
      generation aromatase inhibitor letrozole inhibits estrogen production, and is
      more efficacious than the estrogen receptor inhibitor tamoxifen. In recent years,
      letrozole has been widely used to treat postmenopausal breast cancers in People's
      Republic of China. Also, metastatic, premenopausal, and male breast cancers have
      been effectively treated by a combination of letrozole with cytotoxic, radiation,
      or other therapies. In this review, we provide a perspective and summary of
      recent advances in the use of letrozole for breast cancer in Chinese patients. 

PMID- 27042101
TI  - Prognostic value of preoperative lymphocyte-to-monocyte ratio in pancreatic
      adenocarcinoma.
AB  - BACKGROUND: Inflammation and immunity have an important role in the development
      of cancer. The lymphocyte-to-monocyte ratio (LMR) has been shown to be of
      prognostic value in several malignant forms. The purpose of this study was to
      analyze the prognostic significance of preoperative LMR in post-curative
      resection of pancreatic adenocarcinoma. METHODS: A total of 144 patients with
      primary pancreatic adenocarcinoma who underwent curative operation were enrolled
      in this retrospective study. The correlation between preoperative LMR and
      survival was analyzed using Kaplan-Meier curves and multivariate Cox regression
      analyses. RESULTS: In the univariate analysis, an elevated preoperative LMR was
      significantly associated with an increased overall survival (OS) (19 months vs 12
      months, P=0.000), and this result remained significant in the multivariate
      analysis (hazard ratio [HR]: 0.148; 95% confidence interval [CI]: 0.085-0.252;
      P=0.000). Furthermore, patients with high LMR also had higher median recurrence
      free survival (RFS) than patients with low LMR in univariate (18 months vs 10
      months, P=0.000) and multivariate analyses (HR: 0.148; 95% CI: 0.085-0.252;
      P=0.000). Subgroup analyses showed that both patients with stage III cancer and
      patients with stage I+II cancer can obtain OS and RFS benefits from high LMR.
      CONCLUSION: LMR can be considered as an independent prognostic biomarker for
      operable pancreatic adenocarcinoma.

PMID- 27042102
TI  - Benefit from thoracic radiotherapy in patients with extensive-disease small-cell
      lung cancer with elevated lactate dehydrogenase.
AB  - BACKGROUND: High lactate dehydrogenase (LDH) is associated with a large tumor
      burden in extensive-disease small-cell lung cancer (ED-SCLC). This study
      evaluated the benefit of additional thoracic radiotherapy (TRT) in patients with
      ED-SCLC with elevated LDH. METHODS: We analyzed 94 patients with ED-SCLC and
      evaluated LDH at Sun Yat-sen University Cancer Center during the period between
      January 2000 and March 2010. Patients were divided into two groups according to
      whether TRT was received. Survival was evaluated by the Kaplan-Meier method and
      Cox's regression analysis. RESULTS: The median age of the 94 patients with ED
      SCLC was 58.5 years. The main metastatic sites included the liver, bone, brain,
      and adrenal glands. The response rate in the TRT group was 46.9%. There were 32
      patients (34.04%) receiving TRT and 5.3% receiving prophylactic cranial
      irradiation. The median survival time reached 10 months (95% confidence interval:
      8.22, 11.78 months), and the 1-, 2-, and 5-year survival rates were 43.6%, 11.7%,
      and 2.1%, respectively. There was a significant difference in the median
      progression-free survival (PFS) and overall survival (OS) between the TRT group
      and the no TRT group (PFS: 9.0 months vs 6.0 months, P=0.018; OS: 13.0 months vs
      9.0 months, P=0.006). CONCLUSION: The use of TRT improves the survival of
      patients with ED-SCLC. Future studies should use the LDH level for categorizing
      patients for treatment.

PMID- 27042103
TI  - Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular
      zones in relation to tumor control outcomes of patients with glioblastoma
      multiforme.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain
      tumor with high relapse rate. In this study, we aimed to determine if dose
      escalated (DE) radiotherapy improved tumor control and survival in GBM patients.
      METHODS: We conducted a retrospective analysis of 49 and 23 newly-diagnosed
      histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy
      (2.33 Gy per fraction) and conventional doses (60 Gy), respectively, between 2007
      and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm
      expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical
      cavity, respectively. Bilateral subventricular zones (SVZ) were contoured on a co
      registered pre-treatment magnetic resonance imaging and planning computed
      tomography dataset as a 5 mm wide structure along the lateral margins of the
      lateral ventricles. Survival outcomes of both cohorts were compared using log
      rank test. Radiation dose to SVZ in the DE cohort was evaluated. RESULTS: Median
      follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated
      cohorts, respectively. Median overall survival (OS) of patients who received DE
      radiotherapy was 15.2 months (95% confidence interval [CI] =11.0-18.6), while
      median OS of the latter cohort was 18.4 months (95% CI =12.5-31.4, P=0.253).
      Univariate analyses of clinical and dosimetric parameters among the DE cohort
      demonstrated a trend of longer progression-free survival, but not OS, with
      incremental radiation doses to the ipsilateral SVZ (hazard ratio [HR] =0.95, 95%
      CI =0.90-1.00, P=0.052) and proportion of ipsilateral SVZ receiving 50 Gy (HR
      =0.98, 95% CI =0.97-1.00, P=0.017). CONCLUSION: DE radiotherapy did not improve
      survival in patients with GBM. Incorporation of ipsilateral SVZ as a radiotherapy
      target volume for patients with GBM requires prospective validation.

PMID- 27042104
TI  - miR-429 functions as a tumor suppressor by targeting FSCN1 in gastric cancer
      cells.
AB  - It has been previously reported that the deregulation of microRNAs in gastric
      cancer (GC) was correlated with the progression and prognosis. miR-429, a member
      of the miR-200 family, was previously shown to play an important role in human
      carcinomas. Our study shows that miR-429 is significantly downregulated in GC
      tissues compared with matched nontumor tissues. Overexpression of miR-429 in GC
      cells suppressed cell proliferation. Fascin-1 (FSCN1) was identified as one of
      the targets of miR-429 and knockdown of FSCN1 mimics the function of miR-429
      overexpression. In conclusion, miR-429 acts as a tumor suppressor by targeting
      FSCN1, suggesting that miR-429 and FSCN1 can both be potential therapeutic
      targets of GC. 

PMID- 27042105
TI  - Cytogenetic abnormality in patients with multiple myeloma analyzed by fluorescent
      in situ hybridization.
AB  - OBJECTIVE: To analyze the fluorescent in situ hybridization (FISH) data and the
      association with clinical characteristics, therapy response, and survival time in
      patients with multiple myeloma. METHOD: We performed a retrospective review of
      patients with multiple myeloma from November 2010 to April 2014. RESULTS:
      Cytogenetic abnormalities by FISH were detectable in 66% of patients. One
      cytogenetic abnormality, two cytogenetic abnormalities, and complex abnormalities
      were detectable in 21.2%, 51.5%, and 27.3% of cases, respectively. 1q21
      amplification, t(4p16.3/14q32), and 17p deletion were observed in 69.7%, 30.3%,
      and 21.2% of cases, respectively. Total response rates (complete response [CR] +
      near CR + partial response) were 93.8% and 82.1%, respectively, in cytogenetic
      normality group and abnormality group. CR rates were 50% and 32.1%, respectively.
      Median overall survival (OS) time was 51 months and 24 months, respectively, in
      cytogenetic normality group and abnormality group (P<0.05). Median OS time was
      not significantly different between 1q21 amplification group and no 1q21
      amplification group in patients with FISH abnormalities (P>0.05). Median OS time
      was not significantly different between t(4;14) group and no t(4;14) group in
      patients with FISH abnormalities (P>0.05). Seven patients of 17p deletion died in
      2 years. CONCLUSION: Multiple myeloma is characterized by a high occurrence of
      chromosomal aberrations. 1q21 amplification and t(4;14) are the most common
      abnormalities. Multiple cytogenetic abnormalities are frequently observed in the
      same one patient. The total response rate, CR rate, and OS time are worse in
      cytogenetic abnormal patients compared with cytogenetic normal patients. Patients
      with 17p deletion have a very poor prognosis. Future goals of therapy will be to
      achieve minimal residual disease, biomarkers, and genomic data, which might
      provide a better estimate of the depth of response to therapy and OS.

PMID- 27042106
TI  - Prognostic role of microRNA-150 in various carcinomas: a meta-analysis.
AB  - OBJECTIVE: MicroRNA-150 (miR-150) was revealed to be an attractive prognostic
      biomarker in recent studies. However, the prognostic significance of miR-150
      expression in cancer remains inconclusive. The aim of this study was to summarize
      the global predicting role of miR-150 in survival in patients with various
      carcinomas. METHODS: Eligible studies were identified through multiple search
      strategies. Data were extracted from the studies by investigating the
      relationship between miR-150 expression and survival in patients with cancer. A
      meta-analysis of the hazard ratio (HR) was then performed to evaluate the
      prognostic role of miR-150 in different tumors. Pooled HRs of miR-150 for overall
      survival and progression-free survival were calculated to measure the effect of
      miR-150 expression on prognosis. RESULTS: This meta-analysis included nine
      published studies concerning various carcinomas. Our results indicate that an
      elevated miR-150 expression is associated with an enhanced overall survival in
      the digestive tract cancer subgroup (HR =0.57, 95% confidence interval [CI]: 0.37
      0.90) and a poor progression-free survival in various cancers (HR =3.08, 95% CI:
      2.00-4.75). CONCLUSION: miR-150 may have the potential to become a new useful
      prognostic factor to monitor cancer prognosis and progression. However, given the
      current insufficient relevant data, further clinical studies are needed.

PMID- 27042107
TI  - A dried blood spot mass spectrometry metabolomic approach for rapid breast cancer
      detection.
AB  - OBJECTIVE: Breast cancer (BC) is still a lethal threat to women worldwide. An
      accurate screening and diagnosis strategy performed in an easy-to-operate manner
      is highly warranted in clinical perspective. Besides the routinely focused
      protein markers, blood is full of small molecular metabolites with diverse
      structures and properties. This study aimed to screen metabolite markers with BC
      diagnosis potentials. METHODS: A dried blood spot-based direct infusion mass
      spectrometry (MS) metabolomic analysis was conducted for BC and non-BC
      differentiation. The targeted analytes included 23 amino acids and 26
      acylcarnitines. RESULTS: Multivariate analysis screened out 21 BC-related
      metabolites in the blood. Regression analysis generated a diagnosis model
      consisting of parameters Pip, Asn, Pro, C14:1/C16, Phe/Tyr, and Gly/Ala. Tested
      with another set of BC and non-BC samples, this model showed a sensitivity of
      92.2% and a specificity of 84.4%. Compared to the routinely used protein markers,
      this model exhibited distinct advantage with its higher sensitivity. CONCLUSION:
      Blood metabolites screening is a more plausible approach for BC detection.
      Furthermore, this direct MS analysis could be finished within few minutes, which
      means that its throughput is higher than the currently used imaging techniques.

PMID- 27042108
TI  - Comparison of preoperative neutrophil-lymphocyte, lymphocyte-monocyte, and
      platelet-lymphocyte ratios in patients with upper urinary tract urothelial
      carcinoma undergoing radical nephroureterectomy.
AB  - PURPOSE: The aim of this study was to investigate the prognostic value of
      preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR),
      and lymphocyte-monocyte ratio (LMR) in patients with upper urinary tract
      urothelial carcinoma (UUTUC). METHODS: We retrospectively analyzed the clinical
      data of 140 patients with UUTUC who underwent radical nephroureterectomy from
      January 2005 to December 2011. We plotted receiver operating characteristic
      curves of NLR, PLR, and LMR for the diagnosis of tumor recurrence. Survival
      analysis was performed using the Kaplan-Meier method and log-rank test.
      Independent risk factor analysis was performed using a Cox proportional hazards
      regression model. RESULTS: Receiver operating characteristic curves showed that
      NLR was superior to PLR and LMR as a predictive factor in patients with UUTUC
      undergoing radical nephroureterectomy. Univariate analysis revealed that NLR
      (P<0.001 and P<0.001), PLR (P=0.01 and P<0.001), and LMR (P<0.001 and P<0.001)
      were significantly associated with disease-free survival and progression-free
      survival (PFS), respectively. Multivariate analysis identified NLR and LMR as
      independent prognostic factors for disease-free survival (P=0.035 and P=0.002)
      and PFS (P=0.005 and P=0.002), respectively. CONCLUSION: NLR and LMR could be
      independent predictors of disease-free survival and PFS, and NLR is a superior
      predictive factor to LMR.

PMID- 27042109
TI  - Ovarian small-cell carcinoma hypercalcemic type successfully treated: a case
      report and literature review.
AB  - Ovarian small-cell carcinoma hypercalcemic type (OSCCHT) is a relatively rare and
      highly fatal gynecological malignancy. Prognosis is generally poor, and no
      treatment guidelines are offered. Here, we report a case of OSCCHT successfully
      treated by complete excision and a postoperative chemotherapy scheme of
      carboplatin and paclitaxel. A 29-year-old female with with pelvic mass and
      significantly increased serum calcium (4.90 mmol/L) was referred to our hospital
      on August 22, 2013. Abdominal ultrasonography and computed tomography revealed a
      pelvic nonhomogeneous echo of a 113*102 mm mass, possibly coming from the adnexa
      of the uterus. Preoperative examinations indicated high levels of serum calcium
      and relevant acute renal dysfunction; hence, continuous renal replacement therapy
      was performed until all tests reached minimum operation requirements.
      Interestingly, after excision, serum calcium levels decreased rapidly and
      therefore, extra calcium had to be taken in order to take the level back up to
      normal. The patient was diagnosed with OSCCHT based on the clinical data and
      pathological examinations. After six cycles of chemotherapy, the patient was in a
      good condition and on follow-up there were no signs of recurrence. 

PMID- 27042110
TI  - The effect of antagonizing RGD-binding integrin activity in papillary thyroid
      cancer cell lines.
AB  - Patients with papillary thyroid cancer (PTC) generally have good prognosis, but
      inoperable and radioactive iodine-refractory PTC still poses significant clinical
      challenges due to lack of effective treatment and higher mortality rates. Given
      the important role of integrins in multiple steps of tumor development, integrin
      targeting therapy could be an effective strategy for PTC therapy. In this study,
      we investigated the antitumor effect of antagonizing Arg-Gly-Asp (RGD)-binding
      integrin activity in several PTC cell lines. Two RGD-binding integrin
      heterodimers alphavbeta3 and alphavbeta5 were first determined with fluorescence
      activated cell sorting (FACS) and immunofluorescence assay. Cell proliferation
      and apoptosis were examined by Cell Counting Kit-8 assay and FACS, respectively.
      Cell migration and invasion were determined by transwell assays. All three PTC
      cell lines examined (BCPAP, K1, and TPC1) showed a moderate-to-high expression of
      alphavbeta3 and alphavbeta5 (P<0.05). Antagonizing the two heterodimers with the
      RGD-containing antagonist showed moderate inhibitory effect on cell viability of
      K1 and BCPAP cells, while the inhibitory effect was more significant in TPC1
      cells. Similarly, the apoptotic effect induced by antagonizing alphavbeta3 and
      alphavbeta5 was much stronger in TPC1 cells than in BCPAP and K1 cells. Cell
      migration and invasion were significantly inhibited by alphavbeta3 and
      alphavbeta5 antagonism in all three PTC cell lines. Our results suggested that
      the demonstrated expression of RGD-binding integrin on PTC cells provides the
      possibility of integrin-targeting treatment in PTC. The strong apoptotic effect
      observed in TPC1 cells indicated that a subgroup of PTC patients may benefit from
      the cytotoxic effect of RGD-binding integrin antagonism, while the strong
      inhibitory effect on migration and invasion in all three PTC cells by
      antagonizing alphavbeta3 and alphavbeta5 showed there is an exciting possibility
      that targeting RGD-binding integrin may serve a potential therapeutic approach
      for metastatic PTC patients. 

PMID- 27042111
TI  - Antitumor activity of pluripotent cell-engineered vaccines and their potential to
      treat lung cancer in relation to different levels of irradiation.
AB  - Cancer stem cells (CSCs) are critical for tumor initiation/maintenance and
      recurrence or metastasis, so they may serve as a potential therapeutic target.
      However, CSC-established multitherapy resistance and immune tolerance render
      tumors resistant to current tumor-targeted strategies. To address this, renewable
      multiepitope-integrated spheroids based on placenta-derived mesenchymal stem
      cells (pMSCs) were X-ray-modified, at four different irradiation levels,
      including 80, 160, 240, and 320 Gy, as pluripotent biologics, to inoculate hosts
      bearing Lewis lung carcinoma (LL2) and compared with X-ray-modified common LL2
      cells as control. We show that the vaccines at the 160/240 Gy irradiation levels
      could rapidly trigger tumor cells into the apoptosis loop and evidently prolong
      the tumor-bearing host's survival cycle, in contrast to vaccines irradiated at
      other levels (P<0.05), with tumor-sustaining stromal cell-derived factor-1/CXCR4
      pathway being selectively blockaded. Meanwhile, almost no or minimal toxicity was
      detected in the vaccinated hosts. Importantly, 160/240 Gy-irradiated vaccines
      could provoke significantly higher killing of CSCs and non-CSCs, which may
      provide an access to developing a novel biotherapy against lung carcinoma. 

PMID- 27042112
TI  - Increased expression of the long noncoding RNA CRNDE-h indicates a poor prognosis
      in colorectal cancer, and is positively correlated with IRX5 mRNA expression.
AB  - BACKGROUND: The long noncoding RNA (lncRNA) colorectal neoplasia differentially
      expressed - h (CRNDE-h) plays important roles in the early stages of human
      development and cancer progression. We investigated the expression and clinical
      significance of lncRNA CRNDE-h in colorectal cancer (CRC). METHODS: The
      expression level of lncRNA CRNDE-h was analyzed in 142 CRC tissues and 142 paired
      adjacent nontumorous tissues, along with 21 inflammatory bowel diseases, 69
      hyperplastic polyp, and 73 colorectal adenoma samples, using quantitative real
      time polymerase chain reaction. The association between lncRNA CRNDE-h, and
      Iroquois homeobox protein 5 (IRX5) mRNA was examined in the same 142 CRC tissues.
      RESULTS: We found that lncRNA CRNDE-h level was elevated in the CRC and adenoma
      groups compared with the other groups (all at P<0.001). In CRC, upregulation of
      lncRNA CRNDE-h was significantly correlated with large tumor size, positive
      regional lymph node metastasis, and distant metastasis (all at P<0.05). Area
      under the curve for lncRNA CRNDE-h showed diagnostic capability for
      distinguishing CRC from other groups. Patients with CRC with high lncRNA CRNDE-h
      expression level had poorer overall survival than those with low lncRNA CRNDE-h
      expression (log-rank test, P<0.001). Further, multivariable Cox regression
      analysis suggested that increased expression of lncRNA CRNDE-h was an independent
      prognostic indicator for CRC (hazard ratio [HR]=2.173; 95% confidence interval
      [CI], 1.282-3.684, P=0.004). Furthermore, lncRNA CRNDE-h expression was
      positively correlated with IRX5 mRNA in CRC tissues. CONCLUSIONS: Our data offers
      convincing evidence for the first time that lncRNA CRNDE-h is associated with
      adverse clinical characteristics and poor prognosis, which suggests that it might
      play an important role in CRC development and progression and might have clinical
      potential as a useful prognostic predictor.

PMID- 27042113
TI  - Predictive value of mutant p53 expression index obtained from nonenhanced
      computed tomography measurements for assessing invasiveness of ground-glass
      opacity nodules.
AB  - PURPOSE: To predict p53 expression index (p53-EI) based on measurements from
      computed tomography (CT) for preoperatively assessing pathologies of nodular
      ground-glass opacities (nGGOs). METHODS: Information of 176 cases with nGGOs on
      high-resolution CT that were pathologically confirmed adenocarcinoma was
      collected. Diameters, total volumes (TVs), maximum (MAX), average (AVG), and
      standard deviation (STD) of CT attenuations within nGGOs were measured. p53-EI
      was evaluated through immunohistochemistry with Image-Pro Plus 6.0. A multiple
      linear stepwise regression model was established to calculate p53-EI prediction
      from CT measurements. Receiver-operating characteristic curve analysis was
      performed to compare the diagnostic performance of variables in differentiating
      preinvasive adenocarcinoma (PIA), minimally invasive adenocarcinoma (MIA), and
      invasive adenocarcinoma (IAC). RESULTS: Diameters, TVs, MAX, AVG, and STD showed
      significant differences among PIAs, MIAs, and IACs (all P-values <0.001), with
      only MAX being incapable to differentiate MIAs from IACs (P=0.106). The mean p53
      EIs of PIAs, MIAs, and IACs were 3.4+/-2.0, 7.2+/-1.9, and 9.8+/-2.7, with
      significant intergroup differences (all P-values <0.001). An equation was
      established by multiple linear regression as: p53-EI prediction =0.001* TVs
      +0.012* AVG +0.022* STD +9.345, through which p53-EI predictions were calculated
      to be 4.4%+/-1.0%, 6.8%+/-1.3%, and 8.5%+/-1.4% for PIAs, MIAs, and IACs (Kruskal
      Wallis test P<0.001; Tamhane's T2 test: PIA vs MIA P<0.001, MIA vs IAC P<0.001),
      respectively. Although not significant, p53-EI prediction has a little higher
      area under the curve (AUC) than the actual one both in differentiating MIAs from
      PIAs (AUC 0.938 vs 0.914, P=0.263) and in distinguishing IACs from MIAs (AUC
      0.812 vs 0.786, P=0.718). CONCLUSION: p53-EI prediction of nGGOs obtained from CT
      measurements allows accurately estimating lesions' pathology and invasiveness
      preoperatively not only from radiology but also from pathology.

PMID- 27042114
TI  - Effects of CYP3A5 genetic polymorphism and smoking on the prognosis of non-small
      cell lung cancer.
AB  - OBJECTIVE: We aimed to explore the impacts of the rs776746 polymorphism in the
      CYP3A5 gene and smoking on the prognosis of non-small-cell lung cancer (NSCLC).
      MATERIALS AND METHODS: Our study enrolled 104 early NSCLC patients undergoing
      surgery and 107 advanced NSCLC patients undergoing chemotherapy, hospitalized
      between December 2009 and December 2012 at the First Affiliated Hospital of
      Liaoning Medical University. All subjects with complete follow-up data were
      pathologically diagnosed. The rs776746 polymorphism and different genotypes
      (*1/*1, *1/*3, and *3/*3) were identified by polymerase chain-reaction
      restriction fragment-length polymorphism. RESULTS: Clinical response to
      chemotherapy in NSCLC patients with *1/*1 + *1/*3 genotypes were significantly
      worse than in those with the *3/*3 genotype (17.78% vs 56.45%, P<0.001), and
      after Bonferroni adjustment, the differences still showed significance (P
      c<0.01). The mortality risk of NSCLC patients undergoing chemotherapy with the
      *3/*3 genotype was 0.617 times those with *1/*1 + *1/*3 genotypes (relative risk
      [RR] 0.617, 95% confidence interval [CI] 0.402-0.948; P=0.028), while the
      mortality risk of smoking patients was 1.743 times greater than that of nonsmoker
      patients (RR 1.743, 95% CI 1.133-2.679; P=0.042). Furthermore, a 3.087-fold
      mortality risk was found in NSCLC patients undergoing surgery with the *3/*3
      genotype compared with those with *1/*1 + *1/*3 genotypes (RR 3.087, 95% CI 1.197
      7.961; P=0.020). In NSCLC patients undergoing surgery, the mortality risk of
      smokers was 1.896 times greater than nonsmokers (RR 1.896, 95% CI 1.040-3.455;
      P=0.037). CONCLUSION: Our study demonstrated that the CYP3A5 rs776746
      polymorphism and smoking may influence the prognosis of NSCLC patients undergoing
      chemotherapy and surgery.

PMID- 27042115
TI  - Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment
      for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta
      analysis.
AB  - PURPOSE: To assess the efficacy of pemetrexed plus platinum doublet chemotherapy
      as first-line treatment for advanced nonsquamous non-small-cell lung cancer
      (NSCLC) through a trial-level meta-analysis. METHODS: Trials published between
      1990 and 2015 were identified by an electronic search of public databases
      (Medline, Embase, and Cochrane Library). All clinical studies were independently
      identified by two authors. Demographic data, treatment regimens, objective
      response rate (ORR), progression-free survival (PFS), and overall survival (OS)
      were extracted and analyzed using comprehensive meta-analysis software (version
      2.0). RESULTS: A total of 2,551 patients with advanced nonsquamous NSCLC from ten
      trials were included for analysis: 1,565 patients were treated with pemetrexed
      plus platinum doublet chemotherapy and 986 with platinum plus other first-line
      chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95%
      confidence interval [CI]: 31.7%-44.3%), with median PFS and OS of 5.7 and 16.05
      months, respectively. When compared to other platinum-based doublet
      chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly
      improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77-0.97, P=0.01) but not PFS (HR
      =0.90, 95% CI: 0.80-1.01, P=0.084) in advanced nonsquamous NSCLC patients.
      CONCLUSION: Pemetrexed plus platinum doublet regimen is an efficacious treatment
      for advanced nonsquamous NSCLC patients. Our findings support the use of
      pemetrexed plus platinum doublet regimen as first-line treatment in advanced
      nonsquamous NSCLC patients because of its potential survival benefits.

PMID- 27042116
TI  - Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a
      meta-analysis.
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an important role
      in tumor progression and metastasis. A number of studies have investigated the
      association of HIF-1alpha with prognosis and clinicopathological characteristics
      of osteosarcoma but yielded inconsistent results. METHOD: Systematic computerized
      searches were performed in PubMed, Embase, and Web of Science databases for
      relevant original articles. The pooled hazard ratios (HRs) and odds ratios (ORs)
      with corresponding confidence intervals (CIs) were calculated to assess the
      prognostic value of HIF-1alpha expression. The standard mean difference was used
      to analyze the continuous variable. RESULTS: Finally, nine studies comprising 486
      patients were subjected to final analysis. Protein expression level of HIF-1alpha
      was found to be significantly related to overall survival (HR =3.0; 95% CI: 1.46
      6.15), disease-free survival (HR =2.23; 95% CI: 1.26-3.92), pathologic grade (OR
      =21.33; 95% CI: 4.60-98.88), tumor stage (OR =10.29; 95% CI: 3.55-29.82),
      chemotherapy response (OR =9.68; 95% CI: 1.87-50.18), metastasis (OR =5.06; 95%
      CI: 2.87-8.92), and microvessel density (standard mean difference =2.83; 95% CI:
      2.28-3.39). CONCLUSION: This meta-analysis revealed that overexpression of HIF
      1alpha is a predictive factor of poor outcomes for osteosarcoma. HIF-1alpha
      appeared to play an important role in prognostic evaluation and may be a
      potential target in antitumoral therapy.

PMID- 27042117
TI  - miR-32 inhibits proliferation, epithelial-mesenchymal transition, and metastasis
      by targeting TWIST1 in non-small-cell lung cancer cells.
AB  - BACKGROUND: By analyzing published microRNA microarray studies, miR-32 was found
      to be markedly reduced in non-small-cell lung cancer (NSCLC) tissues compared
      with that in nontumor tissues. However, little is known about its role and
      molecular mechanism involved in NSCLC development and progression. Here, we
      report the effect of miR-32 on NSCLC cell proliferation, epithelial-mesenchymal
      transition (EMT), and metastasis. METHODS: Quantitative real-time PCR was
      performed to detect the expression level of miR-32 in primary NSCLC cases and
      cell lines. miR-32-overexpressing H1299 and A549 cells were constructed by
      lipofection transfection. MTT, transwell chamber, and Western blot assays were
      used to assess the effect of miR-32 on proliferation, EMT, and metastasis of
      NSCLC cells, respectively. Target prediction and luciferase reporter assays were
      performed to investigate the targets of miR-32. Tumor formation assay in vivo was
      performed to investigate the antitumor effect of miR-32. RESULTS: An inverse
      correlation existed between miR-32 expression level and NSCLC cell proliferation,
      EMT, and metastasis, and upregulation of miR-32 repressed NSCLC cell
      proliferation, EMT, and metastasis. Moreover, we identified and validated that
      TWIST1 was a direct target of miR-32, and miR-32 regulated NSCLC cell
      proliferation, EMT, and metastasis, at least in part via modulation of TWIST1.
      The animal experiments showed that overexpression of miR-32 inhibited the growth
      of NSCLC tumors in vivo.

PMID- 27042118
TI  - Association between APE1 Asp148Glu polymorphism and the risk of urinary cancers:
      a meta-analysis of 18 case-control studies.
AB  - BACKGROUND: Several observational studies suggested that APE1 Asp148Glu was
      significantly associated with urinary cancers; however, the results of published
      studies are inconsistent. MATERIALS AND METHODS: The PubMed and EMBASE were
      searched for case-control studies regarding the association between Asp148Glu and
      the risk of urinary cancers with a time limit of September 12, 2015. Pooled odds
      ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength
      of the association between Asp148Glu and the risk of developing prostate cancer,
      kidney cancer, bladder cancer, as well as all urinary cancers combined. RESULTS:
      A total of 18 case-control studies were included in the analysis. Our meta
      analysis revealed that the inheritance of at least one APE1 148Glu among Asian
      men was associated with a 1.26-fold increase in the risk of developing urinary
      cancers. Meanwhile, APE1 Asp148Glu was significantly associated with the risk of
      prostate cancer. However, there were no significant relationships between the
      APE1 SNP (single nucleotide polymorphism) and all urinary cancers combined and
      bladder cancer and kidney cancer among the men of Caucasian/Asian/African descent
      or all racial/ethnic groups combined. When stratified by the quality score, no
      significant association was found in high-quality studies (score >=7), but a
      significant increased risk of urinary cancers was observed in lower quality
      studies (score <7) (dominant model: OR=1.27, 95% CI=1.11-1.45). CONCLUSION: Our
      meta-analysis suggests that APE1 Asp148Glu was not associated with the risk of
      urinary cancers but might increase the risk of urinary cancers among Asians.
      Stratification by cancer type identified a significant association of Asp148Glu
      with prostate cancer.

PMID- 27042119
TI  - Poorer prognosis in Taiwanese female ever smokers with stage IV lung
      adenocarcinoma who were readministered a tyrosine kinase inhibitor.
AB  - BACKGROUND: Readministering a second epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with
      acquired resistance to an initial EGFR TKI is a common treatment strategy.
      However, the prognostic factors for the second EGFR TKI are still uncertain.
      PATIENTS AND METHODS: In this retrospective study, we enrolled patients with
      stage IV lung adenocarcinoma diagnosed between June 2009 and October 2013 at two
      university-affiliated hospitals in Taiwan. Basic characteristics including age,
      sex, smoking status, performance status, EGFR mutation status, tumor response,
      and progression-free survival (PFS) of the second EGFR TKI (PFS2) were recorded.
      RESULTS: A total of 72 patients with stage IV adenocarcinoma with susceptible
      EGFR gene mutations who had been treated with a second EGFR TKI were enrolled.
      Survival analysis using the Kaplan-Meier method and log-rank test showed a
      significant difference in PFS2 when classifying the patients according to smoking
      history and sex (P=0.0179). When stratifying the patients by sex, a significant
      difference was found in PFS2 between ever smokers and never smokers in the female
      (1.87 vs 4.87 months, P=0.0081) but not in the male (2.83 vs 2.9 months,
      P=0.9605) patients. A reduced multivariate model developed using the backward
      variable selection method showed that only ever smoking remained an independent
      poor prognostic factor for PFS2, and that sex and ever smoking remained
      independent poor prognostic factors for PFS2 in the female patients (hazard ratio
      [HR] =3.386, 95% confidence interval [CI]: 1.015-11.298, P=0.0473). CONCLUSION:
      This study is the first to demonstrate that female ever smokers have a poorer PFS
      if they have acquired resistance to an initial EGFR TKI and receive a second EGFR
      TKI. Further large-scale studies are urgently needed to elucidate the mechanism.

PMID- 27042120
TI  - Expression of Notch 1 receptor associated with tumor aggressiveness in papillary
      thyroid carcinoma.
AB  - AIM: The aim of this study was to assess if the expression of Notch 1 receptor is
      associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs).
      PATIENTS AND METHODS: By searching the electronic medical record system of Xin
      Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the
      hospital between 2013 and 2014 were retrieved. Then, the cases of patients who
      had a history of any other malignancy or whose thyroid tumor specimen was not
      available for assay were rejected. Finally, 68 cases of PTC patients were
      obtained. Formalin-fixed paraffin-embedded tissue blocks of these patients were
      studied by immunohistochemistry to learn the expression of Notch 1 receptor.
      Meanwhile, the clinical data of these patients including sex, age, size of the
      tumor, presence of node metastasis or distant metastasis, and presence of capsule
      invasion and tumor multicentricity were collected. Pearson's chi-square test or
      Fisher's exact test was used for measuring statistical differences in categorical
      variables. All the statistical tests were two-sided. A P-value <0.05 was
      considered to be statistically significant. RESULTS: A total of 19 male and 49
      female PTC patients with a mean age of 44.8+/-13.6 years (range 18-78 years) were
      studied. Notch 1 receptor expression was found in 15/68 (22%) samples of PTC. The
      expression of Notch 1 receptor was significantly associated with tumor size
      (P=0.021), distant metastasis (P=0.008), capsule invasion (P=0.001), tumor
      multicentricity (P=0.018), and age (P=0.033). However, the expression of Notch 1
      receptor was not significantly correlated with node metastasis (P=0.096) and sex
      (P=0.901). CONCLUSION: The expression of Notch 1 receptor is associated with
      tumor aggressiveness in PTC, and may be used as a molecular marker of tumor
      invasiveness in PTC. PTC patients who show positive expression of Notch 1
      receptor may benefit from radioiodine remnant ablation.

PMID- 27042121
TI  - Comparison of single agent versus combined chemotherapy in previously treated
      patients with advanced urothelial carcinoma: a meta-analysis.
AB  - BACKGROUND: Platinum-based chemotherapy is the standard treatment for advanced
      urothelial cancer (UC) and is generally used in the first-line setting. However,
      the optimal salvage treatment for previously treated UC patients is unclear. We
      conducted a systematic review of published clinical trials of single agent versus
      combined chemotherapy as salvage treatment in previously treated UC patients.
      METHODS: Trials published between 1994 and 2015 were identified by an electronic
      search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant
      studies were independently identified by two authors for inclusion. Demographic
      data, treatment regimens, objective response rate (ORR), disease control rate
      (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4
      toxicities were extracted and analyzed using Comprehensive Meta Analysis software
      (Version 2.0). RESULTS: Fifty cohorts with 1,685 patients were included for
      analysis: 814 patients were treated with single agent chemotherapy and 871 with
      combined chemotherapy. Pooled OS was significantly higher at 1 year for combined
      chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37;
      P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064).
      Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI:
      1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to
      single agent for advanced UC patients. As for grade 3 and 4 toxicities, more
      frequencies of leukopenia and thrombocytopenia were observed in the combined
      chemotherapy than in single agent group, while equivalent frequencies of anemia,
      nausea, vomiting, and diarrhea were found between the two groups. CONCLUSION: In
      comparison with single agent alone, combined chemotherapy as salvage treatment
      for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not
      2-year OS. Our findings support the need to compare combined chemotherapy with
      single agent alone in the salvage setting in large prospective trials due to its
      potential survival benefit in advanced UC patients.

PMID- 27042122
TI  - Impact of diabetes mellitus on the survival of pancreatic cancer: a meta
      analysis.
AB  - BACKGROUND: Diabetes mellitus (DM) is a risk factor for pancreatic cancer (PC),
      but its prognostic value in PC is still unclear. To elucidate this issue, we
      systematically reviewed the evidence concerning the association between diabetes
      status and PC. METHODS: Medline and EMBASE databases were searched to identify
      the eligible studies. Overall and subgroup analyses were performed to detect the
      discrepancy of prognosis according to diabetes status. Hazard ratios (HRs) with
      95% CI were used to estimate the effect size. RESULTS: Eighteen studies including
      16,181 patients with sample size ranging from 113 to 4,658 were pooled in this
      meta-analysis. Results showed that patients with DM had worse survival (HR 1.19,
      95% CI: 1.07-1.32). In view of the impact of diabetes duration and tumor stage on
      the outcomes, we classified the studies into different groups. The results
      indicated that DM was associated with survival in both long-standing diabetes (HR
      1.26, 95% CI: 1.14-1.40) and recent-onset diabetes (HR 1.29, 95% CI: 1.09-1.51).
      Data regarding localized disease (HR 1.57, 95% CI: 1.00-2.46) and nonlocalized
      (locally advanced and metastatic) disease (HR 1.42, 95% CI: 1.16-1.73) verified
      that the prognostic value was independent of tumor stage. CONCLUSION: Our results
      suggested that patients with DM were associated with worse survival than those
      without DM. Diabetes may be a predictive factor of survival in patients with PC.
      Surveillance of diabetes status and antidiabetes medication administration after
      the diagnosis of PC is of clinical importance.

PMID- 27042123
TI  - Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant
      treatment with different epidermal growth factor receptor phenotypes.
AB  - PURPOSE: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)
      have demonstrated efficacy in treating advanced non-small-cell lung cancer
      (NSCLC). Preliminary findings suggested that EGFR-TKIs might also be beneficial
      in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate
      the efficacy and safety of neoadjuvant therapy with icotinib in patients with
      early-stage NSCLC. PATIENTS AND METHODS: We retrospectively reviewed the medical
      history of patients who were initially diagnosed with stage IA-IIIA NSCLC and
      were under icotinib administration before surgery between December 2011 and
      December 2014. Tumor assessment was conducted between the second and fourth week
      from initial icotinib treatment. The association between personal
      characteristics, smoking status, disease stage, EGFR mutation status, and
      clinical outcomes were investigated using multivariate logistic regression
      analysis. RESULTS: A total of 67 patients with NSCLC were reviewed, and
      approximately half (38/67) of them were identified as having EGFR-mutant tumors.
      The overall response rate of all patients was 26.7% at 2-4 weeks' assessment.
      Multivariate analysis showed that female sex (38.5% versus 10.7% in males,
      P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011)
      were independent predictive factors. The analysis also showed that the most
      common adverse effects were rash (43.3%) and dry skin (34.4%), which were
      tolerable. CONCLUSION: Icotinib induced clinical response with minimal toxicity
      as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR
      mutations. Further studies are warranted to confirm our findings.

PMID- 27042124
TI  - Decreased FOXF1 promotes hepatocellular carcinoma tumorigenesis, invasion, and
      stemness and is associated with poor clinical outcome.
AB  - Forkhead box F1 (FOXF1), a member of the forkhead transcription factor
      superfamily, plays critical roles in the progression of certain types of cancers.
      However, the expression and function of FOXF1 in human hepatocellular carcinoma
      (HCC) are still unclear. Quantitative real-time reverse transcription polymerase
      chain reaction, Western blotting, and immunohistochemistry detected the
      relatively lower expression status of FOXF1 in HCC cases. Soft agar and transwell
      assays clearly demonstrated that FOXF1-knockdown cells showed significantly
      increased in vitro cell tumorigenesis and invasion, and FOXF1-overexpressing
      cells had significantly reduced growth and invasion potential. Our study also
      examined the role of FOXF1 in HCC cell stemness by sphere formation, aldehyde
      dehydrogenase (ALDH1) activity, and CD44/133-positive cell analysis. Enforced
      FOXF1 expression decreased HCC cell stemness, and the downregulation of FOXF1
      promoted cancer cell stemness. The in vivo study showed that overexpressed FOXF1
      inhibits nude mouse tumorigenicity with downregulation of CD44 and proliferating
      cell nuclear antigen. More importantly, loss of FOXF1 expression was linked to
      poor overall survival time by Kaplan-Meier analysis. 

PMID- 27042125
TI  - Efficacy of multimodal treatment for leptomeningeal metastases in a lung cancer
      harboring an EGFR mutation.
AB  - For lung cancer patients with epidermal growth factor receptor (EGFR) mutations,
      the advent of EGFR tyrosine kinase inhibitors (TKIs) has prolonged survival
      rates. Even though disease sites have been well controlled by EGFR-TKIs, some
      patients develop carcinomatous meningitis, which reduces their quality of life
      drastically. Although multidisciplinary approaches have improved patient survival
      and quality of life, the outcomes are not yet satisfactory. We report the case of
      a 54-year-old Japanese woman diagnosed with leptomeningeal metastases (LM) from a
      lung adenocarcinoma harboring an EGFR exon 21 L858R point mutation. She was
      treated with gefitinib for 2 months, and symptoms of LM emerged during the
      treatment period. Although the treatment was switched to erlotinib, disturbance
      of consciousness worsened because of progressive hydrocephalus. Because all
      extracranial lesions remained responsive to treatment, and the exon 20 T790M
      point mutation was not detected in cerebrospinal fluid, we placed a
      ventriculoperitoneal shunt. The patient's disturbed consciousness improved
      dramatically after the shunt was placed; however, the optic and auditory nerve
      impairments due to direct invasion of LM lesions into nerve canals persisted.
      Administration of bevacizumab subsequent to whole-brain radiotherapy reduced the
      cranial nerve impairment, and the patient survived for 10 months. In conclusion,
      a combination of erlotinib and ventriculoperitoneal shunt was effective for
      hydrocephalus, and the immediate administration of additional therapies,
      including bevacizumab and radiation therapy, was useful in a patient suffering
      from LM. 

PMID- 27042126
TI  - A meta-analysis of clinical trials assessing the effect of radiofrequency
      ablation for breast cancer.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive thermal
      ablation technique. We conducted a meta-analysis based on eligible studies to
      assess the efficacy and safety of RFA for treating patients with breast cancer.
      METHODS: A literature search was conducted in PubMed, Embase, and Web of Science
      databases. Eligible studies were clinical trials that assessed RFA in patients
      with breast cancer. The outcomes included complete ablation rate, recurrence
      rate, excellent or good cosmetic rates, and complication rate. A random-effects
      or fixed-effects model was used to pool the estimate, according to the
      heterogeneity among the included studies. RESULTS: Fifteen studies, with a total
      of 404 patients, were included in this meta-analysis. Pooled results showed that
      89% (95% confidence interval: 85%-93%) of patients achieved a complete ablation
      after RFA treatment and 96% of patients reported a good-to-excellent cosmetic
      result. Although the pooled result for recurrence rate was 0, several cases of
      relapse were observed at different follow-up times. No RFA-related complications
      were recorded, except for skin burn with an incidence of 4% (95% confidence
      interval: 1%-6%). CONCLUSION: This meta-analysis showed that RFA can be a
      promising alternative option for treating breast cancer since it produces a
      higher complete ablation rate with a low complication rate. Further well-designed
      randomized controlled trials are needed to confirm the efficacy and safety of RFA
      for breast cancer.

PMID- 27042127
TI  - Tremelimumab: research and clinical development.
AB  - The immune checkpoint therapy is a relatively recent strategy that aims to tweak
      the immune system to effectively attack cancer cells. The understanding of the
      immune responses and their regulation at the intracellular level and the
      development of fully humanized monoclonal antibodies are the pillars of an
      approach that could elicit durable clinical responses and even remission in some
      patients with cancer. Most of the immune checkpoints that regulate the T-cell
      responses (activation and inhibition) operate through proteins present on the
      cytoplasmic membrane of the immune cells. Therefore, specific antibodies capable
      of blocking the inhibitory signals should lead to unrestrained immune responses
      that supersede the inhibitory mechanisms, which are naturally present in the
      tumor microenviroment. The best-known and most successful targets for immune
      checkpoint therapy are the cytotoxic T-lymphocyte antigen-4 and programmed cell
      death-1 coreceptors. Tremelimumab (CP-675,206) is a fully humanized monoclonal
      antibody specific for cytotoxic T-lymphocyte antigen-4, which has been
      successfully used to treat patients with metastatic melanoma and some other
      cancers. Although still a work in progress, the use of tremelimumab as an immune
      checkpoint therapeutic agent is a promising approach alone or in combination with
      other anticancer drugs. Here, we review the use of this antibody in a number of
      clinical trials against solid tumors. 

PMID- 27042128
TI  - miR-98 functions as a tumor suppressor in salivary adenoid cystic carcinomas.
AB  - PURPOSE: miR-98, a member of the let-7 family of microRNAs, is downregulated in
      many malignant tumors and has been correlated with tumor progression. However,
      the roles of miR-98 in salivary adenoid cystic carcinomas (SACCs) are still
      unclear. Thus, we explored the role of miR-98 in the pathogenesis of SACCs.
      METHODS: Reverse transcription-polymerase chain reaction was used to quantify miR
      98 expression in SACC cell lines as well as in the primary tumors and adjacent
      tissues. Target gene prediction was carried out using softwares such as miRanda,
      PicTar, and TargetScan, and the neuroblastoma RAS viral oncogene homologue (N
      RAS) was chosen as a potential target gene. Subsequently, the regulatory role of
      miR-98 on N-RAS expression was examined by Western blotting and
      immunofluorescence assays. N-RAS expression was detected in SACC tissues and SACC
      cell lines using immunohistochemistry and Western blot, respectively.
      Furthermore, the associations between N-RAS expression and clinicopathological
      features were analyzed. Finally, the effects of miR-98 on the proliferation and
      metastasis of SACC cell lines were determined. RESULTS: miR-98 was downregulated
      in primary tissues and ACC-M cells. Meanwhile, N-RAS expression was significantly
      higher in SACC tissues than that in the adjacent tissues, and its overexpression
      was significantly associated with the clinical stage and tumor size. In addition,
      the overexpression of miR-98 in ACC-M cells inhibited cell proliferation,
      invasion, and migration in vitro. It also significantly decreased the expression
      of N-RAS and inhibited signaling through the PI3K/AKT and MAPK/ERK pathways.
      CONCLUSION: These results indicate that miR-98 possibly acts as a tumor
      suppressor in SACC by negatively regulating the oncogene N-RAS.

PMID- 27042129
TI  - Nasal polyps in patients with asthma: prevalence, impact, and management
      challenges.
AB  - Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have
      coexisting asthma under the concept of "United Airway Disease", being the
      combination of both diseases, which is one of the most challenging phenotypes to
      treat. Although clinicians have recognized this difficult-to-treat phenotype for
      many years, it remained poorly characterized. There is increasing epidemiological
      evidence linking chronic rhinosinusitis and asthma, but a good understanding of
      the pathophysiology and the combined management is still lacking. Bronchial
      asthma is more prevalent in patients who suffer chronic rhinosinusitis, while
      asthmatic patients have a greater prevalence of CRSwNP than patients without
      asthma. The effect of CRSwNP treatment, whether medical or surgical, in asthma is
      today less controversial after some studies have shown improvement of asthma
      after medical and/or surgical treatment of CRSwNP. However, direct comparisons
      between surgical and medical treatments are limited. Further randomized clinical
      trials are, however, still needed to better understand the management when both
      asthma and CRSwNP occur together. This review aims at summarizing the prevalence,
      impact, and management challenges regarding both asthma and CRSwNP. 

PMID- 27042130
TI  - Effects of long-term exercise training on adipose tissue expression of
      fractalkine and MCP-1 in patients with type 2 diabetes and stable coronary artery
      disease: a substudy of a randomized controlled trial.
AB  - PURPOSE: Adipose tissue inflammation plays a role in atherosclerosis and type 2
      diabetes (T2DM). We aimed to investigate whether 12 months of exercise training
      in patients with both T2DM and coronary artery disease (CAD) reduced the genetic
      expression of the proinflammatory markers fractalkine (CX3CL1) and its receptor
      (CX3CR1) and monocyte chemoattractant protein-1 (MCP-1) in the subcutaneous
      adipose tissue. Expression of the genes in the circulating leukocytes and
      circulating levels of the markers were also investigated. PATIENTS AND METHODS: A
      total of 137 patients with T2DM and CAD were included to study the effects of
      exercise on atherosclerosis progression and glucose control. Patients were
      randomized to exercise training (combined aerobic and strength training) or
      control. At inclusion and after 12 months, fasting blood samples and a
      subcutaneous adipose tissue sample were taken. RNA was extracted from the adipose
      tissue and circulating leukocytes, and the expression levels were examined by
      reverse transcription-polymerase chain reaction. Circulating fractalkine and MCP
      1 were determined by enzyme-linked immunosorbent assay. RESULTS: The analyses
      were performed in 114 patients who completed the study and adhered to the
      intervention principle. At baseline, gene expression of fractalkine and CX3CR1 in
      the adipose tissue was similar in the two groups. There were no change within
      either group and no between-group differences in changes from baseline.
      Circulating fractalkine increased after 12 months in the exercise group
      (P=0.044), significantly more compared to controls (P=0.042), however only in the
      patients with advanced vascular disease. Neither the expression levels of MCP-1
      nor the circulating levels changed significantly in either group. At baseline,
      CX3CR1 expression in the adipose tissue was associated with body mass index
      (P<0.001). CONCLUSION: No significant effects of long-term exercise training on
      adipose tissue expression of fractalkine, CX3CR1, or MCP-1 were found in our
      patients with combined CAD and T2DM. However, a slight increase in circulating
      fractalkine after the intervention was recorded. The association of CX3CR1
      expression with body mass index might indicate increased immune activation in the
      adipose tissue.

PMID- 27042131
TI  - Genistein treatment increases bone mass in obese, hyperglycemic mice.
AB  - BACKGROUND: Obesity and type 2 diabetes mellitus are associated with elevated
      risk of limb bone fracture. Incidences of these conditions are on the rise
      worldwide. Genistein, a phytoestrogen, has been shown by several studies to
      demonstrate bone-protective properties and may improve bone health in obese type
      2 diabetics. METHODS: In this study, we test the effects of genistein treatment
      on limb bone and growth plate cartilage histomorphometry in obese, hyperglycemic
      ob/ob mice. Six-week-old ob/ob mice were divided into control and genistein
      treated groups. Genistein-treated mice were fed a diet containing 600 mg
      genistein/kg for a period of 4 weeks. Cross-sectional geometric and
      histomorphometric analyses were conducted on tibias. RESULTS: Genistein-treated
      mice remained obese and hyperglycemic. However, histomorphometric comparisons
      show that genistein-treated mice have greater tibial midshaft diameters and
      ratios of cortical bone to total tissue area than the controls. Genistein-treated
      mice also exhibit decreased growth plate thickness of the proximal tibia.
      CONCLUSION: Our results indicate that genistein treatment affects bone of the
      tibial midshaft in the ob/ob mouse, independent of improvements in the
      hyperglycemic state and body weight.

PMID- 27042132
TI  - Sodium-glucose cotransporter-2 inhibitor combination therapy to optimize glycemic
      control and tolerability in patients with type 2 diabetes: focus on dapagliflozin
      metformin.
AB  - In type 2 diabetes (T2D), early combination therapy using agents that target a
      number of the underlying pathophysiologic defects contributing to hyperglycemia
      may improve patient outcomes. For many patients, the combination of metformin
      with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor may be a good option
      because these agents have complementary mechanisms of action, neutral-to-positive
      effects on body weight, and a low risk of hypoglycemia. This review focuses on
      the combination of metformin with dapagliflozin, a member of the SGLT-2 inhibitor
      class of antidiabetes agents. In clinical trials, the combination of
      dapagliflozin with metformin produced significant and sustained reductions in
      glycated hemoglobin and body weight in a broad range of adult patients with T2D,
      including those initiating pharmacotherapy and those with more advanced disease.
      These reductions were accompanied by modest decreases in blood pressure.
      Dapagliflozin as add-on therapy to metformin was well tolerated and associated
      with low rates of hypoglycemia. Genital infections and, in some studies, urinary
      tract infections were more frequent with dapagliflozin than with placebo. Early
      combination therapy with dapagliflozin and metformin may be a safe and
      appropriate treatment option that enables patients with T2D to achieve
      individualized glycemic goals as either initial combination therapy in treatment
      naive patients or as dapagliflozin add-on in patients inadequately controlled
      with metformin therapy. 

PMID- 27042133
TI  - Childhood obesity: prevention is better than cure.
AB  - Obesity and its associated comorbidities have emerged as a major health problem
      garnering interests from both public health agencies and mainstream media
      consumers. With increasing awareness on its impact on health, finances, and
      community at large, it has come to the forefront for scientific research and
      development of health plans. The need for better strategies and novel
      interventions to manage obesity is now being recognized by the entire health care
      system. Obesity and overweight is now the fifth leading global risk factor for
      mortality. Strategic investment is thus urgently needed to implement population
      based childhood obesity prevention programmes which are effective and also
      culturally appropriate. Population-based prevention is crucial to stem this
      rising tide of childhood obesity which is fast reaching epidemic proportions.
      Obesity has its onset very early in life; therefore, children constitute a major
      group of this disease. It is thus imperative to lay utmost importance on
      prevention of obesity in children and herald its progress, if present already.
      Furthermore, treatment is still in preliminary stage, so early prevention holds
      better than treatment at later stages. This article is an attempt to lay emphasis
      on childhood obesity as a problem that needs to be recognized early and measures
      for its prevention. 

PMID- 27042134
TI  - Hematological indices and their correlation with fasting blood glucose level and
      anthropometric measurements in type 2 diabetes mellitus patients in Gondar,
      Northwest Ethiopia.
AB  - BACKGROUND: Diabetes mellitus is (DM) a global public health problem and a
      complex disease characterized by chronic hyperglycemia that leads to long-term
      macrovascular and microvascular complications. Recent studies have reported the
      role of hematological indices in contributing to the vascular injury in diabetic
      patients. Thus, the aim of this study was to determine hematological indices and
      their correlation with fasting blood glucose level and anthropometric measurement
      in type 2 DM patients in comparison with healthy controls. METHODS: A comparative
      cross-sectional study was conducted at the chronic illness clinic of Gondar
      University Hospital from February to April 2015. A total of 296 participants (148
      cases and 148 healthy controls) were selected using systematic random sampling
      technique. Data were collected using a pretested structured questionnaire.
      Fasting blood glucose levels and hematological indices were determined by using
      Bio Systems A25 and Sysmex-KX 21N analyzers, respectively. Independent sample t
      test, Mann-Whitney U-test, and correlation statistics were used. A P-value <0.05
      was considered as statistically significant. RESULT: There was significant
      difference in red blood cell distribution width (47.3+/-2.6 fL vs 45.2+/-3 fL)
      between diabetic patients and controls. Total white blood cells in 10(3)/uL
      (6.59+/-1.42 vs 5.56+/-1.38), absolute lymphocyte count in 10(3)/uL (2.60+/-0.70
      vs 2.04+/-0.63), and absolute neutrophil count in 10(3)/uL (3.57+/-1.46 vs 3.11+/
      1.04) increased significantly in diabetic patients compared with controls,
      respectively. Among platelet indices, mean platelet volume (10.4+/-1.1 fL vs
      9.9+/-1.1 fL) and platelet distribution width (14.5+/-2.1 fL vs 13.4 +/-2.1 fL)
      were found to be significantly increased in the diabetic patients (P<0.05).
      Anthropometric measurements significantly correlated with white blood cell and
      platelet indices. CONCLUSION: The study showed statistically significant
      difference in some hematological parameters of diabetic patients compared to
      controls. Thus, hematological indices could be useful indicators of vascular
      complication and glycemic control in type 2 DM patients.

PMID- 27042135
TI  - A placebo-controlled, double-blind clinical trial to evaluate the efficacy of
      Imedeen((r)) Time Perfection((r)) for improving the appearance of photodamaged
      skin.
AB  - OBJECTIVE: To assess the efficacy of Imedeen Time Perfection for improving the
      appearance and condition of photoaged skin in healthy women. METHODS: This
      randomized, double-blind, placebo-controlled clinical trial enrolled healthy
      women, 35-60 years of age, with Fitzpatrick I-III and Glogau II-III skin types
      and mild-to-moderate facial fine lines/wrinkles. The eligible subjects were
      randomized to receive two tablets daily of either Imedeen Time Perfection
      (Imedeen) or a matching placebo for 12 weeks. Efficacy assessments included
      investigator rating of 16 photoaging parameters (ie, global facial appearance and
      15 individual facial parameters and the average of all parameters),
      instrumentation (ie, ultrasound dermal density, moisture level of the stratum
      corneum, transepidermal water loss, cutometry), and subjects' self-assessment.
      Differences in the mean change from baseline to week 12 values on these outcomes
      were compared between Imedeen and placebo using analysis of variance or a paired
      t-test. RESULTS: Seventy-four subjects with primarily Fitzpatrick skin type III
      (78%-79%) and Glogau type III (53%-58%) completed the study (Imedeen: n=36;
      placebo: n=38). The mean difference in change from baseline to week 12 for global
      facial assessment significantly favored Imedeen over placebo (-0.52; P=0.0017).
      Additionally, the mean differences in the average of all facial photoaging
      parameters (-0.29), mottled hyperpigmentation (-0.25), tactile laxity (-0.24),
      dullness (-0.47), and tactile roughness (-0.62) significantly favored Imedeen
      over placebo (P<=0.05). Significantly greater increases in ultrasound dermal
      density (+11% vs +1%; P<=0.05) and stratum corneum moisturization (+30% vs +6%;
      P<=0.05) were also observed for Imedeen than for placebo. There were no
      significant differences on other instrumental outcomes. CONCLUSION: The results
      of this study suggest that Imedeen Time Perfection can positively affect the
      appearance of photoaged skin, moisturization, and skin density over 12 weeks of
      treatment.

PMID- 27042136
TI  - Identifying factors associated with clinical success in patients treated with
      NASHA((r))/Dx injection for fecal incontinence.
AB  - PURPOSE: Injection with the bulking agent consisting of non-animal stabilized
      hyaluronic acid/dextranomer (NASHA((r))/Dx) is well tolerated and efficacious for
      the treatment of fecal incontinence (FI); however, the patient population that
      may derive maximum benefit has not been established. This post hoc responder
      analysis assessed demographic and baseline characteristics predictive of
      responsiveness to NASHA/Dx treatment. METHODS: Adults with a Cleveland Clinic
      Florida fecal incontinence score (CCFIS) >=10 were randomized to receive NASHA/Dx
      or sham treatment. The primary end point was response to treatment (ie, decrease
      from baseline of >=50% in number of FI episodes) at 6 months; a prespecified
      secondary end point was change in fecal incontinence quality of life (FIQL) score
      at 6 months. Post hoc subgroup analyses were performed for baseline and
      demographic characteristics and prior FI treatments. RESULTS: Overall, response
      to treatment was significantly greater with NASHA/Dx versus sham injection (52.7%
      vs 32.1%; P=0.0089). All subgroups analyzed demonstrated evidence of improvement,
      favoring NASHA/Dx versus sham treatment for both response to treatment and change
      in the FIQL coping/behavior subscale score. For the primary end point, a
      significantly greater percentage of patients with CCFIS <=15, FI symptoms <=5
      years' duration, or obstetric causes of FI responded to NASHA/Dx treatment versus
      patients receiving sham treatment (51.1% vs 28.3%, P=0.0169; 55.4% vs 25.7%,
      P=0.0026; and 53.6% vs 23.1%, P=0.0191, respectively). The mean change in the
      FIQL coping/behavior score significantly favored NASHA/Dx versus sham treatment
      for patients with CCFIS <=15 (P=0.0371), FI symptoms <=5 years' duration
      (P=0.0289), or obstetric causes of FI (P=0.0384). Patients without a history of
      specific FI treatments (eg, antidiarrheal medications, biofeedback, surgery) were
      more likely to respond to NASHA/Dx versus sham treatment for both end points.
      CONCLUSION: Although all subgroups analyzed showed evidence of quantitative and
      qualitative benefit from NASHA/Dx therapy, patients with characteristics
      indicative of mild-to-moderate FI may exhibit the greatest benefit.

PMID- 27042138
TI  - Categorizing the severity of pain using questions from the 2012 National Health
      Interview Survey.
AB  - BACKGROUND: Based on qualitative and mixed-method approaches, Miller and Loeb
      have proposed a coding system that combines questions on pain persistence and
      bothersomeness to create discrete categories of increasing pain severity for use
      in large population-based surveys. In the current analyses, using data from the
      2012 National Health Interview Survey, we quantitatively assess the pain category
      definitions proposed by Miller and Loeb and compare this original definition to
      ten alternative definitions. METHODS: Using multivariate analysis of variance,
      each definition was related simultaneously to four dependent measures - the
      Kessler 6 score for measuring psychological distress, the number of health
      related bed-disability days, the number of visits to a health professional, and
      the number of emergency room visits. Following the protocol of Serlin et al, the
      definition yielding the largest F score was considered the optimal definition.
      RESULTS: The Miller and Loeb definition produced the largest F value (185.87),
      followed consecutively by several alternative definitions #5 (184.17), #10
      (180.95), and #9 (179.5). A nearly identical ordering was found when looking at
      the mean F value generated from 100 random samples. We also examined the
      frequencies with which each alternative definition achieved the optimal F value
      over the 100 random samples. Only two definitions had achieved the optimal F
      value >5% of the time: the Miller and Loeb definition was optimal 46% of the
      time, while alternative definition #5 was optimal 41% of the time. Similar
      results were seen in subpopulations with back pain and joint pain. CONCLUSION:
      Additional support was provided for the Miller and Loeb coding of pain
      persistence and bothersomeness to produce discrete categories of increasing pain
      severity. This two-question coding scheme may prove to be a viable option for
      assessing pain severity in clinical settings where clinician time and patient
      burden are limiting factors.

PMID- 27042137
TI  - Recent insights into the molecular pathogenesis of Crohn's disease: a review of
      emerging therapeutic targets.
AB  - Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in
      gastroenterology, due to a pathological mechanism that is difficult to explain
      and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is
      one of the main entities in IBD, characterized by clinical polymorphism and great
      variability in the treatment response. Modern theories on the pathogenesis of CD
      have proven that gut microbiome and environmental factors lead to an abnormal
      immune response in a genetically predisposed patient. Genome-wide association
      studies in patients with CD worldwide revealed several genetic mutations that
      increase the risk of IBD and that predispose to a more severe course of disease.
      Gut microbiota is considered a compulsory and an essential part in the
      pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different
      bacterial strains can be found in all patients with IBD. The discovery of
      Escherichia coli entero-invasive on resection pieces in patients with CD now
      increases the likelihood of antimicrobial or vaccine-type treatments. Recent
      studies targeting intestinal immunology and its molecular activation pathways
      provide new possibilities for therapeutics. In addition to antitumor necrosis
      factor molecules, which were a breakthrough in IBD, improving mucosal healing and
      resection-free survival rate, other classes of therapeutic agents come to focus.
      Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent
      cellular immune response. In addition to anti-integrin antibodies, chemokine
      receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging
      results in clinical trials. Micro-RNAs have demonstrated their role as disease
      biomarkers but it could also become useful for the treatment of IBD. Moreover,
      cellular therapy is another therapeutic approach under development, aimed for
      severe refractory CD. Other experimental treatments include intravenous
      immunoglobulins, exclusive enteral nutrition, and granulocyte colony-stimulating
      factors. 

PMID- 27042139
TI  - Psychosocial management of chronic pain in patients with rheumatoid arthritis:
      challenges and solutions.
AB  - There are numerous reviews and meta-analyses that confirm that psychological
      therapy is efficacious for patients with rheumatoid arthritis (RA) in terms of
      managing pain. Therefore, the literature has moved on to answer additional
      questions: 1) What types of interventions are most strongly supported by the
      current evidence? 2) Do different patients benefit from different approaches? 3)
      When is it best to intervene? 4) What modalities are best for administering the
      intervention? 5) What model of care should we be proposing that will result in
      widespread implementation and will ensure access for patients with RA? This
      review concludes that cognitive behavioral therapy (CBT) is the most efficacious
      treatment for pain management in RA; however, there are indications that
      mindfulness may have particular benefits for patients with a history of
      depression. CBT is most effective when administered early in the course of the
      disease. However, there is at present little evidence to confirm whether or not
      psychosocial interventions are effective for patients with comorbid psychological
      disorders. One of the major challenges is ensuring access to effective
      interventions for patients, particularly early on in the course of the disease,
      with a view to preventing physical and psychological morbidity. A stepped-care
      model is proposed; however, we urgently need more, better-quality trials of
      minimal interventions, particularly in Internet-delivered CBT, which appears
      promising and may form the cornerstone of future stepped-care models for
      providing psychosocial care to patients with RA. 

PMID- 27042140
TI  - The MEDD myth: the impact of pseudoscience on pain research and prescribing
      guideline development.

PMID- 27042142
TI  - Magnitude of visceral leishmaniasis and poor treatment outcome among HIV
      patients: meta-analysis and systematic review.
AB  - BACKGROUND: Visceral leishmaniasis (VL) coinfection with HIV/AIDS most often
      results in unfavorable responses to treatment, frequent relapses, and premature
      deaths. Scarce data are available, regarding the magnitude and poor treatment
      outcomes of VL-HIV coinfection. OBJECTIVE: The main objective of this systematic
      review was to describe the pooled prevalence of VL and poor treatment outcome
      among HIV patients. REVIEW METHODS: Electronic databases mainly PubMed were
      searched. Databases, such as Google and Google scholar, were searched for gray
      literature. Articles were selected based on their inclusion criterion, whether
      they included HIV-positive individuals with VL diagnosis. STATA 11 software was
      used to conduct a meta-analysis of pooled prevalence of VL-HIV coinfection.
      RESULTS: Fifteen of the 150 articles fulfilled the inclusion criteria. A majority
      of the study participants were males between 25 years and 41 years of age. The
      pooled prevalence of VL-HIV coinfection is 5.2% with 95% confidence interval of
      (2.45-10.99). Two studies demonstrated the impact of antiretroviral treatment on
      reduction in relapse rate compared with patients who did not start antiretroviral
      treatment. One study showed that the higher the baseline CD4+ cell count (>100
      cells/mL) the lower the relapse rate. Former VL episodes were identified as risk
      factors for relapse in two articles. In one of the articles, an earlier bout of
      VL remains significant in the model adjusted to other variables. CONCLUSION: The
      pooled prevalence of VL in HIV-infected patients is low and an earlier bout of VL
      and CD4+ count <100 cells/mL at the time of primary VL diagnosis are factors that
      predict poor treatment outcome.

PMID- 27042143
TI  - The use of autologous serum for the treatment of ocular surface disease at a
      Swedish tertiary referral center.
AB  - PURPOSE: The study aims to describe an intact cohort with mixed ocular surface
      disease (OSD) treated with autologous serum (AS) eye drops in a tertiary eye
      center. PATIENTS AND METHODS: All cases (n=32 eyes, 24 patients) treated with AS
      for OSD at the Department of Ophthalmology, Sahlgrenska University Hospital,
      Molndal, between 2002 and 2013 were included and medical records were reviewed
      retrospectively. RESULTS: Mean duration of treatment with 20% AS was 28.3+/-56.1
      (median: 12, range: 3-217) days. The most common indication for AS treatment was
      a persistent epithelial defect (PED), which was seen in 16 eyes of 14 patients.
      Mean duration of PED prior to treatment was 19.3+/-18.9 (median: 10, range: 5-68)
      days. Complete or partial epithelial healing occurred in nine eyes (56.2%). The
      remaining seven eyes (44%) did not respond to treatment or data were missing. The
      second group consisted of nine eyes of five patients with superficial punctate
      keratitis (SPK) secondary to dry eye syndrome. Complete or partial healing of the
      epithelium occurred in five eyes (56%), and the remaining four eyes (44%) were
      lost to follow-up. A third group included five eyes with AS as an adjuvant
      treatment after corneal perforation, whereas a fourth group consisted of one
      patient with dry eye after laser-assisted in situ keratomileusis (LASIK).
      CONCLUSION: In this cohort, patients with PED or SPK responded well to treatment
      with AS. Standardized preparation protocols, defined optimal serum concentrations
      for various indications, and large randomized clinical trials are needed to fully
      comprehend the role of AS in the treatment of OSD.

PMID- 27042144
TI  - Detection of the mutation may guide treatment of heart and muscle in Duchenne
      muscular dystrophy.

PMID- 27042141
TI  - Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease with
      a high incidence and is the most common genetic cause of infant mortality. SMA is
      primarily characterized by degeneration of the spinal motor neurons that leads to
      skeletal muscle atrophy followed by symmetric limb paralysis, respiratory
      failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1)
      gene shifts the load of expression of SMN protein to the SMN2 gene that produces
      low levels of full-length SMN protein because of alternative splicing, which are
      sufficient for embryonic development and survival but result in SMA. The
      molecular mechanisms of the (a) regulation of SMN gene expression and (b)
      degeneration of motor neurons caused by low levels of SMN are unclear. However,
      some progress has been made in recent years that have provided new insights into
      understanding of the cellular and molecular basis of SMA pathogenesis. In this
      review, we have briefly summarized recent advances toward understanding of the
      molecular mechanisms of regulation of SMN levels and signaling mechanisms that
      mediate neurodegeneration in SMA. 

PMID- 27042145
TI  - Mixed cryoglobulinemia-associated Sjogren's syndrome leading to spontaneous
      rupture of the kidney: a case report.
AB  - BACKGROUND: Spontaneous rupture of the kidney is uncommon and is mainly caused by
      renal tumors. Only a few cases are caused by vasculitis. We report here the first
      case of spontaneous rupture of kidney resulting from mixed cryoglobulinemia. CASE
      PRESENTATION: A 44-year-old man presented with sudden onset of fever, acute
      pulmonary edema, left flank abdominal pain unassociated with trauma, and rapidly
      progressive renal failure requiring dialysis. Computed tomography of the abdomen
      revealed a large perirenal hematoma of the left kidney. During conservative
      surgery, the patient underwent renal biopsy that showed renal vasculitis and
      membranoproliferative glomerulonephritis with intracapillary microthrombi. Tests
      were positive for mixed cryoglobulinemia caused by Sjogren's syndrome. The
      patient was better after immunosuppressive therapy, with the disappearance of
      clinical symptoms and the recovery of baseline renal function. CONCLUSION: We
      report on this case and discuss a possible link between spontaneous rupture of
      kidney and mixed cryoglobulinemia-associated Sjogren's syndrome.

PMID- 27042146
TI  - Clinical effectiveness and safety of powered exoskeleton-assisted walking in
      patients with spinal cord injury: systematic review with meta-analysis.
AB  - BACKGROUND: Powered exoskeletons are designed to safely facilitate ambulation in
      patients with spinal cord injury (SCI). We conducted the first meta-analysis of
      the available published research on the clinical effectiveness and safety of
      powered exoskeletons in SCI patients. METHODS: MEDLINE and EMBASE databases were
      searched for studies of powered exoskeleton-assisted walking in patients with
      SCI. Main outcomes were analyzed using fixed and random effects meta-analysis
      models. RESULTS: A total of 14 studies (eight ReWalkTM, three EksoTM, two
      Indego((r)), and one unspecified exoskeleton) representing 111 patients were
      included in the analysis. Training programs were typically conducted three times
      per week, 60-120 minutes per session, for 1-24 weeks. Ten studies utilized flat
      indoor surfaces for training and four studies incorporated complex training,
      including walking outdoors, navigating obstacles, climbing and descending stairs,
      and performing activities of daily living. Following the exoskeleton training
      program, 76% of patients were able to ambulate with no physical assistance. The
      weighted mean distance for the 6-minute walk test was 98 m. The physiologic
      demand of powered exoskeleton-assisted walking was 3.3 metabolic equivalents and
      rating of perceived exertion was 10 on the Borg 6-20 scale, comparable to self
      reported exertion of an able-bodied person walking at 3 miles per hour.
      Improvements in spasticity and bowel movement regularity were reported in 38% and
      61% of patients, respectively. No serious adverse events occurred. The incidence
      of fall at any time during training was 4.4%, all occurring while tethered using
      a first-generation exoskeleton and none resulting in injury. The incidence of
      bone fracture during training was 3.4%. These risks have since been mitigated
      with newer generation exoskeletons and refinements to patient eligibility
      criteria. CONCLUSION: Powered exoskeletons allow patients with SCI to safely
      ambulate in real-world settings at a physical activity intensity conducive to
      prolonged use and known to yield health benefits.

PMID- 27042148
TI  - Cognitive behavioral therapy for suicidal behaviors: improving patient outcomes.
AB  - This systematic review provides an overview of the effectiveness of cognitive
      behavioral therapy (CBT) in reducing suicidal cognitions and behavior in the
      adult population. We identified 15 randomized controlled trials of CBT for adults
      (aged 18 years and older) that included suicide-related cognitions or behaviors
      as an outcome measure. The studies were identified from PsycINFO searches,
      reference lists, and a publicly available database of psychosocial interventions
      for suicidal behaviors. This review identified some evidence of the use of CBT in
      the reduction of both suicidal cognitions and behaviors. There was not enough
      evidence from clinical trials to suggest that CBT focusing on mental illness
      reduces suicidal cognitions and behaviors. On the other hand, CBT focusing on
      suicidal cognitions and behaviors was found to be effective. Given the current
      evidence, clinicians should be trained in CBT techniques focusing on suicidal
      cognitions and behaviors that are independent of the treatment of mental illness.

PMID- 27042147
TI  - Managing ankle ligament sprains and tears: current opinion.
AB  - The purpose of this paper is to present a current review of pathoanatomical
      features, differential diagnosis, objective assessment, intervention, and
      clinical course associated with managing lateral ankle ligament sprains. Proper
      diagnosis and identification of affected structures should be obtained through
      history and objective assessment. From this information, an individualized
      evidence-based intervention plan can be developed to enable recovery while
      decreasing the risk of reinjury. An appropriate evaluation is needed not only to
      determine the correct diagnosis but also to allow for grading and determining the
      prognosis of the injury in those with an acute lateral ankle sprain. Examination
      should include an assessment of impairments as well as a measure of activity and
      participation. Evidence-based interventions for those with an acute lateral ankle
      sprain should include weight bearing with bracing, manual therapy, progressive
      therapeutic exercises, and cryotherapy. For those with chronic ankle instability
      (CAI), interventions should include manual therapy and a comprehensive
      rehabilitation program. It is essential to understand the normal clinical course
      for athletes who sustain a lateral ankle sprain as well as risk factors for an
      acute injury and CAI. Risk factors for both an acute lateral ankle sprain and CAI
      include not using an external support and not participating in an appropriate
      exercise program. Incorporating the latest evidence-based rehabilitation
      techniques provides the best course of treatment for athletes with an acute ankle
      sprain or CAI. 

PMID- 27042149
TI  - Severe Ophthalmological Complications of Thyroid Disease are Rare in Ibadan,
      Southwestern Nigeria: Results of a Pilot Study.
AB  - BACKGROUND: Ocular manifestations of thyroid dysfunction constitute a wide
      clinical spectrum ranging from minor ocular discomfort, lid retraction, lid lag
      and ocular injection, to sight threatening eyeball protusion and optic nerve
      compression. Thyroid-related eye disorders are most commonly associated with
      Graves' disease, and this most frequently occurs in the setting of
      hyperthyroidism. However, in 10% of cases, typical eye signs have also been
      reported in euthyroid and hypothyroid states. The severity of thyroid eye disease
      has been linked to cigarette smoking. There is very little data specifically
      reporting the ocular manifestations of thyroid disease among black African
      patients and there is no known report from Nigeria. This pilot study therefore
      focused on documenting the ocular signs accompanying thyroid dysfunction in a
      black African population. AIM: To evaluate the pattern of ocular complications,
      among patients treated for thyroid disorders, in a major Nigerian teaching
      hospital. RESULTS: A total of 75 patients with thyroid dysfunction, were
      evaluated, comprising 63 females and 12 males. There was a very low prevalence of
      smoking among patients (<5%). Graves' disease was the commonest thyroid disorder,
      representing 70% of cases. Seventy-eight percent of patients were hyperthyroid,
      11.8% were euthyroid and only 9.8% of patients were hypothyroid. Commonest
      systemic symptoms were neck swelling (68.6%), weight loss (63.8%), tremors
      (60.9%) and palpitations (59.4%). Two-thirds of patients reported ocular symptoms
      consisting mainly of painless eye swelling (66.7%) and ocular irritation (58%).
      Conjunctival injection, lid lag and lid retraction were the commonest ocular
      signs. Chemosis, severe proptosis and ocular motility disorder were very rare.
      Optic neuropathy was found in 4 patients but was related to pre-existing
      glaucoma. Majority of patients required only ocular emollients and tear
      supplements. CONCLUSION: Severe ocular complications of thyroid disorders were
      uncommon in this cross-section of Nigerian patients. This may be linked to the
      very low prevalence of cigarette smoking among Nigerians or genetic and
      environmental factors linked to their African heritage.

PMID- 27042150
TI  - Structure, process, and outcomes of care in a telemonitoring program for patients
      with type 2 diabetes.
AB  - BACKGROUND: Using Donabedian's structure-process-outcomes (SPO) framework, this
      descriptive, exploratory study examined the structure of a telemonitoring program
      in a population of patients with type 2 diabetes (T2D), the process of nurse
      patient telephonic interactions, and patients' clinical outcomes. METHODS:
      Secondary data analysis was conducted using data from 581 patients who
      participated in a home telemonitoring program for 12 months. Three point-biserial
      and six Pearson correlations were estimated to determine how patient demographics
      related to clinical characteristics. Mixed model regressions were conducted
      predicting hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and diastolic
      blood pressure (DBP) levels at 6, 9, and 12 months based on the frequency of
      contact in the earlier 3 months. Analysis of variances were conducted to assess
      if the frequency of contact was significantly different by change in HbA1c levels
      from 3 to 6, 6 to 9, and 9 to 12 months. RESULTS: Significant negative
      correlations were found between age and HbA1c (r=-0.10, P=0.015) and DBP (r=
      0.16, P<0.001), a significant positive correlation was found between age and SBP
      (r=0.15, P=0.001). A significant correlation was found between sex and DBP (r pb=
      0.11, P=0.015); female participants had lower DBP levels than males. Frequency of
      contact was not related to the change in clinical outcomes. However, the
      frequency of contact for the time period 3 to 6 months was associated with change
      in HbA1c for the 6- to 9- month period and frequency of contact during the 6- to
      9- month period was associated with change in HbA1c from 9 to 12 months.
      CONCLUSION: Examination of the SPO measures in the telemonitoring environment
      assisted in understanding the effectiveness of this type of unique intervention
      and the need for further in-depth exploration of self-management techniques among
      individuals with T2D.

PMID- 27042151
TI  - Percutaneous Angioplasty of the Sole Patent Cerebral Artery in Two Patients with
      Takayasu's Aortoarteritis.
AB  - We report two female patients with Takayasu's aortoarteritis, who presented with
      symptoms of cerebral ischemia due to critical stenosis of the sole patent
      cerebral artery. Both had occlusion of both vertebral arteries and one carotid
      artery with critical stenosis of the other carotid artery and presented with
      hemiparesis contralateral to the patent but stenosed cerebral artery. They also
      had transient ischemic attacks attributable to the culprit vessel. In the first
      patient, balloon angioplasty alone was not successful, and hence, a self
      expanding stent was deployed in the right common carotid artery. In the second
      patient, successful balloon angioplasty was performed for the left common carotid
      artery. Distal protection devices were not used, and neither patient experienced
      any periprocedural neurological event. Clinical follow-up at six months revealed
      no significant cerebral events. 

PMID- 27042152
TI  - Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer.
AB  - Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is
      common and results in significant morbidity and mortality. The interaction of
      prostate cancer with the bone microenvironment contributes to progression of
      cancer in the bone leading to skeletal-related events (SREs). Studies aimed at
      targeting the bone have been carried out over the recent years. Bisphosphonates
      are synthetic pyrophosphate analogs first investigated for their role in SRE
      prevention with zoledronic acid as the main bisphosphonate that is approved by
      the US Food and Drug Administration for retardation of skeletal events in men
      with metastatic prostate cancer. Denosumab is another bone-targeted agent against
      uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to
      zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in
      targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing
      strontium or samarium in the remote past, but only radium-223 is the first
      radiopharmaceutical that has yielded improvement in overall survival. The
      combination and sequencing strategies of these agents is the subject of multiple
      ongoing trials to guide the best use of these emerging agents. 

PMID- 27042154
TI  - Diagnostic Implication and Clinical Relevance of Ancillary Techniques in Clinical
      Pathology Practice.
AB  - Hematoxylin-eosin-stained slide preparation is one of the most durable techniques
      in medicine history, which has remained unchanged since implemented. It allows an
      accurate microscopic diagnosis of the vast majority of tissue samples. In many
      circumstances, this technique cannot answer all the questions posed at the
      initial diagnostic level. The pathologist has always been looking for additional
      ancillary techniques to answer pending questions. In our daily histopathology
      practice, we referred to those techniques as special stains, but nowadays, they
      are more than stains and are collectively called ancillary tests. They include a
      wide range of techniques starting from histochemical stains and ending in one or
      more advanced techniques, such as immunohistochemistry, immunofluorescence,
      molecular studies, cytogenetic studies, electron microscopy, flow cytometry, and
      polymerase chain reaction. 

PMID- 27042153
TI  - Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer
      and Strategies to Overcome It.
AB  - The introduction of trastuzumab therapy markedly improved the poor prognosis
      associated with HER2-amplified breast cancers. Despite this, the presence of
      primary and acquired resistance to trastuzumab treatment remains a significant
      common challenge. The identification of resistance mechanisms and the
      incorporation of new drugs that achieve a better blockade of HER family receptors
      signaling have resulted in improved outcomes. The phosphatidylinositol 3'
      kinase/protein kinase B/mammalian target of rapamycin pathway, cross-talk with
      estrogen receptors, immune response, cell cycle control mechanisms, and other
      tyrosine kinase receptors such as insulin-like growth factor I receptor are
      potential pathways involved in trastuzumab resistance. Different therapeutic
      interventions targeting these pathways are currently under evaluation. 

PMID- 27042155
TI  - A suggested emergency medicine boot camp curriculum for medical students based on
      the mapping of Core Entrustable Professional Activities to Emergency Medicine
      Level 1 milestones.
AB  - BACKGROUND: An increasing number of students rank Emergency Medicine (EM) as a
      top specialty choice, requiring medical schools to provide adequate exposure to
      EM. The Core Entrustable Professional Activities (EPAs) for Entering Residency by
      the Association of American Medical Colleges combined with the Milestone Project
      for EM residency training has attempted to standardize the undergraduate and
      graduate medical education goals. However, it remains unclear as to how the EPAs
      correlate to the milestones, and who owns the process of ensuring that an
      entering EM resident has competency at a certain minimum level. Recent trends
      establishing specialty-specific boot camps prepare students for residency and
      address the variability of skills of students coming from different medical
      schools. OBJECTIVE: Our project's goal was therefore to perform a needs
      assessment to inform the design of an EM boot camp curriculum. Toward this goal,
      we 1) mapped the core EPAs for graduating medical students to the EM residency
      Level 1 milestones in order to identify the possible gaps/needs and 2) conducted
      a pilot procedure workshop that was designed to address some of the identified
      gaps/needs in procedural skills. METHODS: In order to inform the curriculum of an
      EM boot camp, we used a systematic approach to 1) identify gaps between the EPAs
      and EM milestones (Level 1) and 2) determine what essential and supplemental
      competencies/skills an incoming EM resident should ideally possess. We then
      piloted a 1-day, three-station advanced ABCs procedure workshop based on the
      identified needs. A pre-workshop test and survey assessed knowledge,
      preparedness, confidence, and perceived competence. A post-workshop survey
      evaluated the program, and a posttest combined with psychomotor skills test using
      three simulation cases assessed students' skills. RESULTS: Students (n=9)
      reported increased confidence in the following procedures: intubation (1.5-2.1),
      thoracostomy (1.1-1.9), and central venous catheterization (1.3-2) (a three-point
      Likert-type scale, with 1= not yet confident/able to perform with supervision to
      3= confident/able to perform without supervision). Psychomotor skills testing
      showed on average, 26% of students required verbal prompting with performance
      errors, 48% with minor performance errors, and 26% worked independently without
      performance errors. All participants reported: 1) increased knowledge and
      confidence in covered topics and 2) overall satisfaction with simulation
      experience. CONCLUSION: Mapping the Core EPAs for Entering Residency to the EM
      milestones at Level 1 identifies educational gaps for graduating medical students
      seeking a career in EM. Educators designing EM boot camps for medical students
      should consider these identified gaps, procedures, and clinical conditions during
      the development of a core standardized curriculum.

PMID- 27042156
TI  - Potential predictors of psychological distress and well-being in medical
      students: a cross-sectional pilot study.
AB  - PURPOSE: Research has consistently found that the proportion of medical students
      who experience high levels of psychological distress is significantly greater
      than that found in the general population. The aim of our research was to assess
      the levels of psychological distress more extensively than has been done before,
      and to determine likely predictors of distress and well-being. SUBJECTS AND
      METHODS: In 2013, students from an Australian undergraduate medical school
      (n=127) completed a questionnaire that recorded general demographics, hours per
      week spent studying, in paid work, volunteer work, and physical exercise; past
      and current physical and mental health, social support, substance use, measures
      of psychological distress (Kessler Psychological Distress Scale, depression,
      anxiety, stress, burnout); and personality traits. RESULTS: Females were found to
      have higher levels of psychological distress than males. However, in regression
      analysis, the effect of sex was reduced to nonsignificance when other variables
      were included as predictors of psychological distress. The most consistent
      significant predictors of our 20 indicators of psychological distress were social
      support and the personality traits of emotional resilience and self-control.
      CONCLUSION: The findings suggest that emotional resilience skills training
      embedded into the medical school curriculum could reduce psychological distress
      among medical students.

PMID- 27042157
TI  - Emotion Socialization Practices in Latina and European American Mothers of
      Preschoolers with Behavior Problems.
AB  - The present study examined mothers' emotion socialization of 3-year-old children
      with behavior problems, to determine whether emotion socialization practices, as
      well as the relation between these practices and child functioning, varied across
      ethnicities. Participants were 134 preschoolers with behavior problems. Mothers
      were European American (n = 96) and Latina American (n = 38; predominately Puerto
      Rican). Audiotaped mother-child interactions were coded for emotion socialization
      behaviors. Latina and European American mothers used similar emotion
      socialization practices on most dimensions. Latina mothers were more likely to
      minimize or not respond to their children's negative affect. However, this
      difference did not appear to have ramifications for children. This study provided
      evidence for both differences and similarities across ethnicities on emotion
      socialization practices.

PMID- 27042158
TI  - Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone
      Tumors.
AB  - Humerus is a common site for malignant tumors. Advances in adjuvant therapies and
      reconstructive methods provide salvage of the upper limb with improved outcomes.
      Reports of limb salvage with total humeral replacement in extensive humeral
      tumors are sparse. We undertook a retrospective study of 20 patients who
      underwent total humeral endoprosthetic replacement as limb salvage following
      excision of extensile malignant tumor from 1990 to 2011. With an average followup
      of 42.9, functional and oncological outcomes were analyzed. Ten patients were
      still alive at the time of review. Mean estimated blood loss was 1131 mL and
      duration of surgery was 314 minutes. Deep infection was encountered in one
      patient requiring debridement while mechanical loosening of ulnar component was
      identified in one patient. Subluxation of prosthetic humeral head was noted in 3
      patients. Mean active shoulder abduction was 12.5 degrees  and active flexion was
      15 degrees . Incompetence of abduction mechanism was the major determinant of
      poor active functional outcome. Mean elbow flexion was 103.5 degrees  with 30.5
      degrees  flexion contracture in 10 patients with good and useful hand function.
      Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment
      option in restoring mechanical stability and reasonable functional results
      without compromising patient survival, with low complication rate. 

PMID- 27042159
TI  - Weight loss reduces basal-like breast cancer through kinome reprogramming.
AB  - BACKGROUND: Obesity is associated with an aggressive subtype of breast cancer
      called basal-like breast cancer (BBC). BBC has no targeted therapies, making the
      need for mechanistic insight urgent. Reducing adiposity in adulthood can lower
      incidence of BBC in humans. Thus, this study investigated whether a dietary
      intervention to reduce adiposity prior to tumor onset would reverse HFD-induced
      BBC. METHODS: Adult C3(1)-Tag mice were fed a low or high fat diet (LFD, HFD),
      and an obese group initially exposed to HFD was then switched to LFD to induce
      weight loss. A subset of mice was sacrificed prior to average tumor latency to
      examine unaffected mammary gland. Latency, tumor burden and progression was
      evaluated for effect of diet exposure. Physiologic, histology and proteomic
      analysis was undertaken to determine mechanisms regulating obesity and weight
      loss in BBC risk. Statistical analysis included Kaplan-Meier and log rank
      analysis to investigate latency. Student's t tests or ANOVA compared variables.
      RESULTS: Mice that lost weight displayed significantly delayed latency compared
      to mice fed HFD, with latency matching those on LFD. Plasma leptin concentrations
      significantly increased with adiposity, were reduced to control levels with
      weight loss, and negatively correlated with tumor latency. HFD increased atypical
      ductal hyperplasia and ductal carcinoma in situ in mammary gland isolated prior
      to mean latency-a phenomenon that was lost in mice induced to lose weight.
      Importantly, kinome analysis revealed that weight loss reversed HFD-upregulated
      activity of PKC-alpha, PKD1, PKA, and MEK3 and increased AMPKalpha activity in
      unaffected mammary glands isolated prior to tumor latency. CONCLUSIONS: Weight
      loss prior to tumor onset protected against the effects of HFD on latency and pre
      neoplastic lesions including atypical ductal hyperplasia and DCIS. Using
      innovative kinomics, multiple kinases upstream of MAPK/P38alpha were demonstrated
      to be activated by HFD-induced weight gain and reversed with weight loss,
      providing novel targets in obesity-associated BBC. Thus, the HFD-exposed
      microenvironment that promoted early tumor onset was reprogrammed by weight loss
      and the restoration of a lean phenotype. Our work contributes to an understanding
      of underlying mechanisms associated with tumor and normal mammary changes that
      occur with weight loss.

PMID- 27042160
TI  - The BH3 mimetic drug ABT-737 induces apoptosis and acts synergistically with
      chemotherapeutic drugs in thyroid carcinoma cells.
AB  - BACKGROUND: Patients with dedifferentiated and anaplastic thyroid carcinomas that
      do not take up radioiodine are resistant to chemotherapeutic treatment and
      external irradiation and thus are difficult to treat. Direct induction of
      apoptosis is a promising approach in these apoptosis-resistant tumor cells. The
      BH3 mimetic ABT-737 belongs to a new class of drugs that target anti-apoptotic
      proteins of the BCL-2 family and facilitate cell death. The purpose of this study
      was to investigate the effect of ABT-737 alone or in combination with
      chemotherapeutic drugs on thyroid carcinoma cell lines. METHODS: A total of 16
      cell lines derived from follicular, papillary, and anaplastic thyroid carcinomas
      were treated with ABT-737. Cell viability was measured with MTT assay. Cell death
      was determined by cell cycle phase distribution and subG1 peak analyses,
      determination of caspase 3/7 activity and caspase cleavage products, lactate
      dehydrogenase (LDH) liberation assays and LC3 analysis by western blot. RESULTS:
      The number of viable cells was decreased in all cell lines examined after ABT-737
      treatment, with IC50 values ranging from 0.73 to 15.6 MUM. Biochemical markers of
      apoptosis like caspase activities, caspase cleavage products and DNA
      fragmentation determined as SubG1 peak were elevated after ABT-737 treatment, but
      no LC3 cleavage was induced by ABT-737 indicating no autophagic processes. In
      combination with doxorubicin and gemcitabine, ABT-737 showed synergistic effects
      on cell viability. CONCLUSIONS: With these experiments we demonstrated the
      efficacy of the BH3 mimetic drug ABT-737 against dedifferentiated thyroid
      carcinoma cells of various histological origins and showed synergistic effects
      with chemotherapeutic drugs. ABT-737-treated cells underwent an apoptotic cell
      death. ABT-737 and related BH3 mimetic drugs, alone or in combination, may thus
      be of value as a new therapeutic option for dedifferentiated thyroid carcinomas.

PMID- 27042161
TI  - Basigin-2 upregulated by receptor activator of NF-kappaB ligand enhances lung
      cancer-induced osteolytic lesions.
AB  - BACKGROUND: Lung cancer bone metastasis causes poor prognosis. Basigin-2, a novel
      cancer-associated biomarker, is upregulated in lung cancer and has been linked
      with tumor progression. But little is known about the role of basigin-2 in lung
      cancer bone metastasis and osteolytic lesion. METHODS: Basigin-2 expression was
      evaluated in biopsy tissue specimens of 20 lung cancer patients with bone
      metastases via immunohistochemistry. Invasion assay and MTT proliferation assay
      were performed to test the invasion and proliferation of lung cancer cell after
      modulated basigin-2 expression. The osteoclastic activity of basigin-2 was
      detected in tibia cancer model by injected of lung cancer cells. The regulation
      role of receptor activator of NF-kappaB ligand (RANKL) on basigin-2 and its
      downstream molecules were measured by real-time quantitative RT-PCR, gelatin
      zymography and western blot analysis. RESULTS: We found that basigin-2 was highly
      expressed in lung cancer bone metastases. Then, we demonstrated that basigin-2
      could promote lung cancer cells invasion, metastasis and proliferation through
      upregulating metalloproteinases-2 (MMP-2), MMP-9 and vascular endothelial growth
      factor (VEGF) expression. The lung cancer cells overexpressing basigin-2 strongly
      induced the osteolytic lesions in immunodeficient mice, which were reduced by
      treatment with basigin-2 blocking antibody. Furthermore, we explored the enhanced
      basigin-2 molecular mechanism in lung cancer bone metastasis. Our results
      indicated the RANKL, pivotal for the control of bone resorption, could increase
      basigin-2 and its downstream molecules MMP-2, MMP-9 and VEGF expression in vitro.
      CONCLUSIONS: Basigin-2 upregulated by RANKL induces MMPs and VEGF, which may
      increase lung cancer cell metastasis ability and support osteoclastic activity.
      Thus, our data suggest important roles for basigin-2 in lung cancer-induced
      osteolytic lesion and implicate this protein potential application as a target
      for lung cancer bone metastasis therapy.

PMID- 27042162
TI  - Hydrogen sulfide modulates chromatin remodeling and inflammatory mediator
      production in response to endotoxin, but does not play a role in the development
      of endotoxin tolerance.
AB  - BACKGROUND: Pretreatment with low doses of LPS (lipopolysaccharide, bacterial
      endotoxin) reduces the pro-inflammatory response to a subsequent higher LPS dose,
      a phenomenon known as endotoxin tolerance. Moreover, hydrogen sulfide (H2S), an
      endogenous gaseous mediator (gasotransmitter) can exert anti-inflammatory
      effects. Here we investigated the potential role of H2S in the development of LPS
      tolerance. THP1 differentiated macrophages were pretreated with the H2S donor
      NaHS (1 mM) or the H2S biosynthesis inhibitor aminooxyacetic acid (AOAA, 1 mM).
      METHODS: To induce tolerance, cells were treated with a low concentration of LPS
      (0.5 MUg/ml) for 4 or 24 h, and then treated with a high concentration of LPS (1
      MUg/ml) for 4 h or 24 h. In in vivo studies, male wild-type and CSE(-/-) mice
      were randomized to the following groups: Control (vehicle); Endotoxemic saline
      for 3 days before the induction of endotoxemia with 10 mg/kg LPS) mg/kg; Tolerant
      (LPS at 1 mg/kg for 3 days, followed LPS at 10 mg/kg). Animals were sacrificed
      after 4 or 12 h; plasma IL-6 and TNF-alpha levels were measured. Changes in
      histone H3 and H4 acetylation were analyzed by Western blotting. RESULTS: LPS
      tolerance decreased pro-inflammatory cytokine production. AOAA did not affect the
      effect of tolerance on reducing cytokine production. Treatment of the cells with
      the H2S donor reduced cytokine production. Induction of the tolerance increased
      the acetylation of H3; AOAA reduced histone acetylation. H2S donation increased
      histone acetylation. Tolerance did not affect the responses to H2S with respect
      to histone acetylation. CONCLUSIONS: In conclusion, both LPS tolerance and H2S
      donation decrease LPS-induced cytokine production in vitro and modulate histone
      acetylation. However, endogenous, CSE-derived H2S does not appear to play a
      significant role in the development of LPS tolerance.

PMID- 27042163
TI  - Dabigatran etexilate for thromboprophylaxis in over 5000 hip or knee replacement
      patients in a real-world clinical setting.
AB  - BACKGROUND: Thromboprophylaxis is recommended for patients undergoing total hip
      or total knee replacement (THR, TKR). An international, open-label, prospective,
      observational, single-arm study in a routine clinical setting was performed to
      assess the safety and efficacy of dabigatran etexilate 220 mg once daily in
      patients undergoing THR or TKR, and in subgroups of patients with potentially
      increased risk of bleeding or venous thromboembolism (VTE). MATERIALS AND
      METHODS: Patients were >=18 years and required to be eligible to receive
      dabigatran 220 mg once daily (first dose 110 mg 1-4 h after THR/TKR surgery)
      according to the European Summary of Product Characteristics. The primary safety
      and efficacy outcomes were incidence of major bleeding events (MBEs), and the
      composite incidence of symptomatic VTE events and all-cause mortality,
      respectively. RESULTS: In total, 5292 patients (median age 64 years) were
      enrolled and received dabigatran (2734 THR and 2558 TKR). Median drug exposure
      was 31 days (THR 34 days; TKR 27 days). Overall incidence of MBEs was 0.72 % (95
      % confidence interval [CI] 0.51, 0.98), and this rate was comparable between
      types of surgery and was not significantly affected by protocol-defined risk
      factors. The overall incidence of symptomatic VTE and all-cause mortality was
      1.04 % (95 % CI 0.78, 1.35); the only significant risk factor was history of VTE
      events (odds ratio 5.59; 95 % CI 2.53, 11.08). A post-hoc analysis showed that
      the incidence of MBEs in this observational study was similar to or lower than
      those reported in previous phase 3 trials. CONCLUSIONS: Results from this
      observational study of dabigatran etexilate administered to patients undergoing
      THR or TKR surgery are reassuring and supportive of those obtained in dabigatran
      phase 3 trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00846807.

PMID- 27042164
TI  - The Maternal Description of Child (MDoC): A New Audiotaped Measure of Maternal
      Affect.
AB  - We report on a new measure of maternal affect from an ongoing multi-site birth
      cohort study with primarily low-income families, the Fragile Families and Child
      Wellbeing Study. At child age of 5 years, mothers were asked to describe their
      child in a short, semi-structured home interview. One innovation of this measure 
      called the Maternal Description of Child (MDoC) - is that it captured maternal
      affect via audiotape rather than videotape. Based on mothers' talk about their
      child, coders scored mothers on Positive Affect, Negative Affect, and Detachment.
      Evidence is presented to support the convergent and predictive validity of these
      scales. Given that objective measures of parenting are generally preferable to
      self-reported measures, further research should determine whether the MDoC can be
      successfully administered by phone. If it can, the MDoC would allow large-scale
      phone surveys to measure maternal affect for the first time.

PMID- 27042165
TI  - CIDER: Enabling Robustness-Power Tradeoffs on a Computational Eyeglass.
AB  - The human eye offers a fascinating window into an individual's health, cognitive
      attention, and decision making, but we lack the ability to continually measure
      these parameters in the natural environment. The challenges lie in: a) handling
      the complexity of continuous high-rate sensing from a camera and processing the
      image stream to estimate eye parameters, and b) dealing with the wide variability
      in illumination conditions in the natural environment. This paper explores the
      power-robustness tradeoffs inherent in the design of a wearable eye tracker, and
      proposes a novel staged architecture that enables graceful adaptation across the
      spectrum of real-world illumination. We propose CIDER, a system that operates in
      a highly optimized low-power mode under indoor settings by using a fast Search
      Refine controller to track the eye, but detects when the environment switches to
      more challenging outdoor sunlight and switches models to operate robustly under
      this condition. Our design is holistic and tackles a) power consumption in
      digitizing pixels, estimating pupillary parameters, and illuminating the eye via
      near-infrared, b) error in estimating pupil center and pupil dilation, and c)
      model training procedures that involve zero effort from a user. We demonstrate
      that CIDER can estimate pupil center with error less than two pixels (0.6 degrees
      ), and pupil diameter with error of one pixel (0.22mm). Our end-to-end results
      show that we can operate at power levels of roughly 7mW at a 4Hz eye tracking
      rate, or roughly 32mW at rates upwards of 250Hz.

PMID- 27042166
TI  - The effects of a fat loss supplement on resting metabolic rate and hemodynamic
      variables in resistance trained males: a randomized, double-blind, placebo
      controlled, cross-over trial.
AB  - BACKGROUND: While it is known that dietary supplements containing a combination
      of thermogenic ingredients can increase resting metabolic rate (RMR), the
      magnitude can vary based on the active ingredient and/or combination of active
      ingredients. The purpose of this study was to examine the effects of a
      commercially available thermogenic fat loss supplement on RMR and hemodynamic
      variables in healthy, resistance trained males. METHODS: Ten resistance-trained
      male participants (29 +/- 9 years; 178 +/- 4 cm; 85.7 +/- 11 kg, and BMI = 26.8
      +/- 3.7) volunteered to participate in this randomized, double-blind, placebo
      controlled cross-over study. Participants underwent two testing sessions
      separated by at least 24 h. On their first visit, participants arrived to the
      laboratory after an overnight fast and a 24-h avoidance of exercise, and
      underwent a baseline RMR, HR, and BP assessment. Next, each participant ingested
      a thermogenic fat loss supplement (TFLS) or a placebo (PLA) and repeated the RMR,
      HR, and BP assessments at 60, 120, and 180 min post-ingestion. During the second
      visit the alternative supplement was ingested and the assessments were repeated
      in the exact same manner. Data were analyzed via a 2-factor [2x4] within-subjects
      repeated measures analysis of variance (ANOVA). Post-hoc tests were analyzed via
      paired samples t-tests. The criterion for significance was set at p <= 0.05.
      RESULTS: A significant main effect for time relative to raw RMR data (p = 0.014)
      was observed. Post-hoc analysis revealed that the TFLS significantly increased
      RMR at 60-min, 120-min, and 180-min post ingestion (p < 0.05) as compared to
      baseline RMR values. No significant changes in RMR were observed for the PLA
      treatment (p > 0.05). Specifically, RMR was increased by 7.8 % (from 1,906 to
      2,057 kcal), 6.9 % (from 1,906 to 2,037 kcal), and 9.1 % (from 1,906 to 2,081
      kcal) in the TFLS, while the PLA treatment increased RMR by 3.3 % (from 1,919 to
      1,981 kcal), 3.1 % (from 1,919 to 1,978 kcal), and 2.1 % (from 1,919 to 1,959
      kcal) above baseline at 60, 120, and 180-min post ingestion, respectively.
      Additionally, the TFLS significantly elevated RMR at the 3-h time point as
      compared to the PLA treatment (2,081 vs 1,959 kcal, p = 0.034). A main effect for
      groups was observed for systolic blood pressure, and a significant interaction
      and main effect for time were observed for diastolic blood pressure. It should be
      noted that although changes in diastolic blood pressure were significant, all
      values stayed within normal clinical ranges (<80 mmHg). CONCLUSIONS: The TFLS led
      to significant elevations in RMR as compared to baseline. These elevations came
      with no adverse effect relative to resting heart rate, but a slight increase in
      blood pressure values. Taken on a daily basis, this TFLS may increase an
      individual's overall energy expenditure, however; future studies should
      investigate if this leads to a reduction in fat mass loss over time.

PMID- 27042167
TI  - Critical evaluation of food intake and energy balance in young modern pentathlon
      athletes: a cross-sectional study.
AB  - BACKGROUND: Modern pentathlon comprises five sports: fencing, swimming,
      equestrian jumping, and a combined event of pistol shooting and running. Despite
      the expected high energy demand of this sport, there are few studies that provide
      support for the nutritional recommendations for pentathletes. The purpose of the
      present study was to evaluate young modern pentathlon athletes with respect to
      body composition, biochemical profile, and consumption of food and supplements.
      METHODS: Fifty-six young modern pentathletes aged 13.5 +/- 2.4 years participated
      in the study: 22 adolescent girls and 34 adolescent boys, weight 55.8 +/- 13.3
      kg, height 1.6 +/- 0.1 m, and body fat 21.1 +/- 3.1 %. Food consumption was
      analyzed through a 24-h recall method and food-frequency questionnaire.
      Assessment of body composition was carried out by checking anthropometric
      measures (body mass, height, and skinfolds) and using protocols according to
      participants' age and sexual maturity. RESULTS: Male participants consumed less
      energy than the general recommendations for athletes from the American Dietetic
      Association (2749 +/- 1024 kcal vs. 3113 +/- 704 kcal, p < 0.01), whereas female
      participants consumed more energy than those recommendations (2558 +/- 808 kcal
      vs. 2213 +/- 4734 kcal, p < 0.01). Neither young men nor young women followed the
      carbohydrate intake recommendations for athletes (6.3 +/- 2.5 g/kg/day and 6.6 +/
      2.2 g/kg/day, respectively). Lipid and protein intakes corresponded to
      recommendations for both sexes; however, insufficient intakes of calcium, fruits,
      and vegetables were seen, as well as frequent consumption of baked goods and
      sugared soft drinks. CONCLUSIONS: Adolescent modern pentathlon athletes presented
      inadequate eating habits with respect to consumption of carbohydrates and energy.
      Many participants had insufficient intake of micronutrients, especially calcium.
      However, future research is needed that is aimed at elucidating the real
      nutritional demands for good physical performance in this sport and the impact of
      inadequate eating habits on performance, especially among young athletes who are
      in the growth-stage years and are exposed to intense physical exercise routines.

PMID- 27042168
TI  - On Statistical Analysis of Neuroimages with Imperfect Registration.
AB  - A variety of studies in neuroscience/neuroimaging seek to perform statistical
      inference on the acquired brain image scans for diagnosis as well as
      understanding the pathological manifestation of diseases. To do so, an important
      first step is to register (or co-register) all of the image data into a common
      coordinate system. This permits meaningful comparison of the intensities at each
      voxel across groups (e.g., diseased versus healthy) to evaluate the effects of
      the disease and/or use machine learning algorithms in a subsequent step. But
      errors in the underlying registration make this problematic, they either decrease
      the statistical power or make the follow-up inference tasks less
      effective/accurate. In this paper, we derive a novel algorithm which offers
      immunity to local errors in the underlying deformation field obtained from
      registration procedures. By deriving a deformation invariant representation of
      the image, the downstream analysis can be made more robust as if one had access
      to a (hypothetical) far superior registration procedure. Our algorithm is based
      on recent work on scattering transform. Using this as a starting point, we show
      how results from harmonic analysis (especially, non-Euclidean wavelets) yields
      strategies for designing deformation and additive noise invariant representations
      of large 3-D brain image volumes. We present a set of results on synthetic and
      real brain images where we achieve robust statistical analysis even in the
      presence of substantial deformation errors; here, standard analysis procedures
      significantly under-perform and fail to identify the true signal.

PMID- 27042169
TI  - Interpolation on the manifold of K component GMMs.
AB  - Probability density functions (PDFs) are fundamental objects in mathematics with
      numerous applications in computer vision, machine learning and medical imaging.
      The feasibility of basic operations such as computing the distance between two
      PDFs and estimating a mean of a set of PDFs is a direct function of the
      representation we choose to work with. In this paper, we study the Gaussian
      mixture model (GMM) representation of the PDFs motivated by its numerous
      attractive features. (1) GMMs are arguably more interpretable than, say, square
      root parameterizations (2) the model complexity can be explicitly controlled by
      the number of components and (3) they are already widely used in many
      applications. The main contributions of this paper are numerical algorithms to
      enable basic operations on such objects that strictly respect their underlying
      geometry. For instance, when operating with a set of K component GMMs, a first
      order expectation is that the result of simple operations like interpolation and
      averaging should provide an object that is also a K component GMM. The literature
      provides very little guidance on enforcing such requirements systematically. It
      turns out that these tasks are important internal modules for analysis and
      processing of a field of ensemble average propagators (EAPs), common in diffusion
      weighted magnetic resonance imaging. We provide proof of principle experiments
      showing how the proposed algorithms for interpolation can facilitate statistical
      analysis of such data, essential to many neuroimaging studies. Separately, we
      also derive interesting connections of our algorithm with functional spaces of
      Gaussians, that may be of independent interest.

PMID- 27042170
TI  - Elastic Stability of Concentric Tube Robots: A Stability Measure and Design Test.
AB  - Concentric tube robots are needle-sized manipulators which have been investigated
      for use in minimally invasive surgeries. It was noted early in the development of
      these devices that elastic energy storage can lead to rapid snapping motion for
      designs with moderate to high tube curvatures. Substantial progress has recently
      been made in the concentric tube robot community in designing snap-free robots,
      planning stable paths, and characterizing conditions that result in snapping for
      specific classes of concentric tube robots. However, a general measure for how
      stable a given robot configuration is has yet to be proposed. In this paper, we
      use bifurcation and elastic stability theory to provide such a measure, as well
      as to produce a test for determining whether a given design is snap-free (i.e.
      whether snapping can occur anywhere in the unloaded robot's workspace). These
      results are useful in designing, planning motions for, and controlling concentric
      tube robots with high curvatures.

PMID- 27042171
TI  - An Efficient Protocol for the Palladium-catalyzed Asymmetric Decarboxylative
      Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II)
      Precatalyst.
AB  - Enantioselective catalytic allylic alkylation for the synthesis of 2-alkyl-2
      allylcycloalkanones and 3,3-disubstituted pyrrolidinones, piperidinones and
      piperazinones has been previously reported by our laboratory. The efficient
      construction of chiral all-carbon quaternary centers by allylic alkylation was
      previously achieved with a catalyst derived in situ from zero valent palladium
      sources and chiral phosphinooxazoline (PHOX) ligands. We now report an improved
      reaction protocol with broad applicability among different substrate classes in
      industry-compatible reaction media using loadings of palladium(II) acetate as low
      as 0.075 mol % and the readily available chiral PHOX ligands. The novel and
      highly efficient procedure enables facile scale-up of the reaction in an
      economical and sustainable fashion.

PMID- 27042172
TI  - Survival of a newborn from a pregnant woman with rabies infection.
AB  - BACKGROUND: Rabies is very common in People's Republic of China. Each year
      thousands of people die because of this disease, but rabies diagnosed in
      pregnancy is very rare. CASE PRESENTATION: In this study, we report the case of a
      pregnant woman who was infected with the rabies virus after a dog bite. The
      symptoms of rabies appeared in labor and she died after pregnancy. Her baby and
      husband did not develop the disease. CONCLUSION: The phenomenon that the newborn
      infant was healthy may be related to the protective role of placenta in resisting
      the invasion of the rabies virus or the absence of systemic viremia. The prompt
      administration of vaccines and anti-rabies immunoglobulin to the infant may have
      also contributed to his survival.

PMID- 27042173
TI  - Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the
      Literature.
AB  - The incidence of melanoma has recently been increasing. BRAF mutations have been
      found in 40-60% of melanomas. The increased activity of BRAF V600E leads to the
      activation of downstream signaling through the mitogen-activated protein kinase
      (MAPK) pathway, which plays a key role as a regulator of cell growth,
      differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma
      with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and
      dabrafenib are two selective BRAF inhibitors approved by the Food and Drug
      Administration (FDA). Both drugs are well tolerated and successfully used in
      clinical practice. However, some adverse reactions have been reported in patients
      in the course of treatment. Cutaneous side effects are the most common adverse
      events among them with a broad spectrum. Both the case reports and several
      original clinical trials reported cutaneous reactions during the treatment with
      BRAF inhibitors. In this review, the common cutaneous side effects of BRAF
      inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were
      reviewed. 

PMID- 27042174
TI  - Characteristics and Risk Factors of Helicobacter pylori Associated Gastritis: A
      Prospective Cross-Sectional Study in Northeast Thailand.
AB  - Background and Aim. Risk factors for Helicobacter pylori infection are genetic
      susceptibility and poor living conditions. This study aimed to investigate the
      Mdm2 gene, clarithromycin resistance, and possible risk factors for Helicobacter
      pylori infection. Methods. Risk factors and clinical characteristics were
      analyzed, including patient demographic data, patient income, personal history,
      possible source of transmission, patient symptoms, endoscopic findings, patterns
      of clarithromycin resistance, and patterns of Mdm2 SNIP309. Results. Ingestion of
      pickled fish (OR = 11.27, 95% CI = 4.31-29.45, p < 0.0001), salt crab (OR = 8.83,
      95% CI = 1.99-39.14, p < 0.001), and Papaya salad (OR = 8.73, 95% CI = 4.54
      16.79, p < 0.01). The prevalence of clarithromycin resistance was 56% (wild type,
      A2143/2142A, is 23.8%; mutation, A2143/2142CG, is 35.7%; wild type + mutation is
      40.5%). The genetic polymorphisms of Mdm2 SNIP309 were SNIP309 T/T homozygous in
      78%, SNIP309 G/T heterozygous in 19%, and SNIP309 G/G homozygous in 3%.
      Conclusion. Pickled fish, salt crab, and Papaya salad are positive risk factors.
      There was high prevalence of clarithromycin resistance. The Mdm2 SNIP309 G/G
      homozygous genotype might be a risk factor for gastric cancer and the fact that
      it is infrequent in Thailand. 

PMID- 27042175
TI  - Protective Role of Ramipril and Candesartan against Myocardial Ischemic
      Reperfusion Injury: A Biochemical and Transmission Electron Microscopical Study.
AB  - The present study was designed to investigate the role of combined administration
      of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion
      injury in rat. Male Wistar albino rats were divided into five groups (n = 6) and
      treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and
      the combination of both drugs, respectively 24 h before induction of global
      ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of
      reflow). Combination of Ramipril and Candesartan when compared to the monotherapy
      significantly increased the levels of superoxide dismutase, reduced glutathione,
      catalase, and nitric oxide and decreased the levels of thiobarbituric acid
      reactive substances. In addition, the superior protective role of combination of
      Ramipril and Candesartan on ischemia induced myocardial damage was further
      confirmed by well preserved myocardial tissue architecture in light microscopy
      and transmission electron microscopy analysis studies. The combination was proved
      to be effective in salvaging the myocardial tissue against ischemic reperfusion
      injury when compared to the monotherapy of individual drugs and further
      investigations on protective mechanism of drugs by increasing the nitric oxide
      level at molecular levels are needed. 

PMID- 27042176
TI  - Ultrasound Guidance for Renal Tract Access and Dilation Reduces Radiation
      Exposure during Percutaneous Nephrolithotomy.
AB  - Purposes. To present our series of 38 prone percutaneous nephrolithotomy
      procedures performed with renal access and tract dilation purely under ultrasound
      guidance and describe the benefits and challenges accompanying this approach.
      Methods. Thirty-eight consecutive patients presenting for percutaneous
      nephrolithotomy for renal stone removal were included in this prospective cohort
      study. Ultrasonographic imaging in the prone position was used to obtain
      percutaneous renal access and guide tract dilation. Fluoroscopic screening was
      used only for nephrostomy tube placement. Preoperative, intraoperative, and
      postoperative procedural and patient data were collected for analysis. Results.
      Mean age of patients was 52.7 +/- 17.2 years. Forty-five percent of patients were
      male with mean BMI of 26.1 +/- 7.3 and mean stone size of 27.2 +/- 17.6
      millimeters. Renal puncture was performed successfully with ultrasonographic
      guidance in all cases with mean puncture time of 135.4 +/- 132.5 seconds. Mean
      dilation time was 11.5 +/- 3.8 min and mean stone fragmentation time was 37.5 +/-
      29.0 min. Mean total operative time was 129.3 +/- 41.1. No patients experienced
      any significant immediate postoperative complication. All patients were rendered
      stone-free and no additional secondary procedures were required. Conclusions.
      Ultrasound guidance for renal access and tract dilation in prone percutaneous
      nephrolithotomy is a feasible and effective technique. It can be performed safely
      with significantly reduced fluoroscopic radiation exposure to the patient,
      surgeon, and intraoperative personnel. 

PMID- 27042177
TI  - A Study on Mortality Profile among Fifty Plus- (50+-) Population (FPP) of India:
      A 5-Year Retrospective Study at New Delhi District.
AB  - Objectives. To find out the mortality profile vis-a-vis different epidemiological
      factors at the time of autopsy among the 50+-Population. Material and Method. A
      five-year retrospective evaluation of medicolegal records between 2006 and 2010
      was done at Lady Hardinge Medical College, New Delhi. Results. A total of 493
      (17.78%) cases belonged to 50+-Population age group out of total 2773 autopsies
      performed. The proportion of unidentified/unknown persons among this age group
      was 36.51%. The unnatural and natural causes constituted 44.62% and 55.38% cases,
      respectively. The unspecified pneumonitis (50.18%) was reported as the commonest
      cause followed by coronary artery disease and respiratory tuberculosis among
      natural ones and the transport accident (57.27%) followed by accidental and
      intentional self-poisoning and exposure to noxious substances and falls among the
      unnatural ones. Conclusion. The findings reveal that this age group most commonly
      dies of natural causes rather than the unnatural ones even in autopsy cases. They
      have definite cure with timely interventions. The study also points out the need
      to devise the road and home safety measures to reduce mortality among the study
      population. 

PMID- 27042178
TI  - Physical Non-Contact Communication between Microscopic Aquatic Species: Novel
      Experimental Evidences for an Interspecies Information Exchange.
AB  - Previous experiments on physical non-contact communication within same species
      gave rise to test for this type of communication also across the species border,
      which was the aim of the present study. It was found that autotrophic unicellular
      organisms (Euglena viridis), separated by cuvettes, affected the proliferation
      rate of heterotrophic unicellular organisms (Paramecium caudatum). Further, the
      heterotrophic unicellular organism affected also the proliferation rate of a
      multicellular heterotrophic organism (Rotatoria sp.) and vice versa. In the case
      when populations (of Euglena viridis and Paramecium caudatum) were shielded
      against electromagnetic fields in the optical spectrum from each other, no
      effects were measured. The results may support the notion that the organisation
      of ecosystems relies also on the exchange of electromagnetic fields from their
      constituting biosystems. 

PMID- 27042179
TI  - Correlation of Beta-2 Adrenergic Receptor Expression in Tumor-Free Surgical
      Margin and at the Invasive Front of Oral Squamous Cell Carcinoma.
AB  - Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and
      is correlated with a wide spectrum of tumor cell mechanisms including
      proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives.
      The present study aimed to analyze the expression of the beta-2 adrenergic
      receptor (beta2-AR) in tumor-free surgical margins of oral squamous cell
      carcinomas (OSCC) and at the invasive front. Sixty-two patients diagnosed with
      OSCC, confirmed by biopsy, were selected for the study. The clinicopathological
      data and clinical follow-up were obtained from medical records and their
      association with beta2-AR expression was verified by the chi-square test or
      Fischer's exact test. To verify the correlation of beta2-AR expression in tumor
      free surgical margins and at the invasive front of OSCCs, Pearson's correlation
      coefficient test was applied. Results. The expression of beta2-AR presented a
      statistically significant correlation between the tumor-free surgical margins and
      the invasive front of OSCC (r = 0.383; p = 0.002). The immunohistochemical
      distribution of beta2-AR at the invasive front of OSCC was also statistically
      significant associated with alcohol (p = 0.038), simultaneous alcohol and tobacco
      consumption (p = 0.010), and T stage (p = 0.014). Conclusions. The correlation of
      beta2-AR expression in OSCC and tumor-free surgical margins suggests a role of
      this receptor in tumor progression and its expression in normal oral epithelium
      seems to be constitutive. 

PMID- 27042180
TI  - A Randomized Case-Series Study Comparing the Stability of Implant with Two
      Different Surfaces Placed in Fresh Extraction Sockets and Immediately Loaded.
AB  - Background. Hydrophilic and moderately rough implant surfaces have been proposed
      to enhance the osseointegration response. Aim. The aim of this study was to
      compare early changes of stability for two implants with identical macrodesign
      but with different surface topographies. Materials and Methods. In 11 patients, a
      total of 22 implants (11 bimodal (minimally rough, control) and 11 proactive
      (moderately rough and hydrophilic, test), Neoss Ltd., Harrogate, UK) were
      immediately placed into fresh extraction sockets and immediately loaded. The peak
      insertion torque (IT) was measured in Ncm at placement. Resonance Frequency
      Analysis (RFA) measurements were made at baseline and 2, 4, 6, and 12 weeks after
      surgery. Results. The two implant types showed similar IT and RFA values at
      placement (NS). A dip of RFA values after 2 weeks followed by an increase was
      observed, where the test implant showed a less pronounced decrease and a more
      rapid recovery than the control implant. The test implants were significantly
      more stable than the control ones after 12 weeks. Conclusions. The results from
      the present study indicated that the hydrophilic and rougher test implant was
      more resistant to immediate loading and showed a significantly higher stability
      than the smoother control implant after 12 weeks. 

PMID- 27042181
TI  - Development and Validation of Chronopotentiometric Method for Imidacloprid
      Determination in Pesticide Formulations and River Water Samples.
AB  - A new electrochemical method for determination of imidacloprid using
      chronopotentiometry on thin film mercury and glassy carbon electrode was
      presented. The most important experimental parameters of chronopotentiometry were
      examined and optimized with respect to imidacloprid analytical signal.
      Imidacloprid provided well-defined reduction peak in Britton-Robinson buffer on
      thin film mercury electrode at -1.0 V (versus Ag/AgCl (KCl, 3.5 mol/L)) and on
      glassy carbon electrode at -1.2 V (versus Ag/AgCl (KCl, 3.5 mol/L)). The
      reduction time was linearly proportional to concentrations from 0.8 to 30.0 mg/L
      on thin film mercury electrode and from 7.0 to 70.0 mg/L on glassy carbon
      electrode. The detection limits were 0.17 mg/L and 0.93 mg/L for thin film
      mercury and glassy carbon electrode, respectively. The estimation of method
      precision as a function of repeatability and reproducibility showed relative
      standard deviations values lower than 3.73%. Recovery values from 97.3 to 98.1%
      confirmed the accuracy of the proposed method, while the constancy of the
      transition time with deliberated small changes in the experimental parameters
      indicated a very good robustness. A minor influence of possible interfering
      compounds proved good selectivity of the method. Developed method was applied for
      imidacloprid determination in commercial pesticide formulations and river water
      samples. 

PMID- 27042184
TI  - Revisiting Nonresidential Environmental Exposures and Childhood Lead Poisoning in
      the US: Findings from Kansas, 2000-2005.
AB  - Although blood lead levels (BLLs) in US children have dramatically declined over
      the past 40 years, there remain pockets of children living in areas with elevated
      BLLs. While some increases (>= 10 MUg/dL) may be associated with legacy lead
      paint, ambient air lead may be contributing to the problem. A deidentified
      dataset of information on over 60,000 Kansas children under 3 years of age who
      were tested for BLL was provided through the Kansas Environmental Public Health
      Tracking Network for the period 2000-2005. Using ArcGIS, we calculated distance
      (in miles) from a lead-emitting industry referred to as a toxic release inventory
      (TRI) site. The USEPA TRI database tracks the management of certain toxic
      chemicals that may pose a threat to human health. US facilities in different
      industry sectors must report annually amount of substances like lead into the
      environment including their exact location. Distance from a TRI site was
      inversely related to BLL after controlling for area-level poverty and pre-1950
      housing. The results of our evaluation indicate there is a significant
      relationship between proximity to lead industry and childhood BLLs. Proximity to
      sources of lead emissions should be evaluated as a possible factor when
      identifying children for targeted BLL testing.

PMID- 27042183
TI  - Mesenchymal Stem Cell-Derived Microvesicles Support Ex Vivo Expansion of Cord
      Blood-Derived CD34(+) Cells.
AB  - Mesenchymal stem cells (MSCs) are known to support the characteristic properties
      of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow
      hematopoietic microenvironment. MSCs are used in coculture systems as a feeder
      layer for the ex vivo expansion of umbilical cord blood (CB) to increase the
      relatively low number of HSPCs in CB. Findings increasingly suggest that MSC
      derived microvesicles (MSC-MVs) play an important role in the biological
      functions of their parent cells. We speculate that MSC-MVs may recapitulate the
      hematopoiesis-supporting effects of their parent cells. In the current study, we
      found MSC-MVs containing microRNAs that are involved in the regulation of
      hematopoiesis. We also demonstrated that MSC-MVs could improve the expansion of
      CB-derived mononuclear cells and CD34(+) cells and generate a greater number of
      primitive progenitor cells in vitro. Additionally, when MSC-MVs were added to the
      CB-MSC coculture system, they could improve the hematopoiesis-supporting effects
      of MSCs. These findings highlight the role of MSC-MVs in the ex vivo expansion of
      CB, which may offer a promising therapeutic approach in CB transplantation. 

PMID- 27042185
TI  - Effects of Xiaoyaosan on Stress-Induced Anxiety-Like Behavior in Rats:
      Involvement of CRF1 Receptor.
AB  - Background. Compared with antidepressant activity of Xiaoyaosan, the role of
      Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects
      of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress
      (CIS) and further explore whether these effects were related to CRF1R signaling.
      Methods. Adult male SD rats were randomly assigned to five groups (n = 12): the
      nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan
      treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin
      treated (surgery) group. Artificial cerebrospinal fluid (0.5 MUL/side) or CRF1R
      antagonist antalarmin (125 ng/0.5 MUL, 0.5 MUL/side) was bilaterally administered
      into the basolateral amygdala in the surgery groups. Except for the nonstressed
      control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30
      minutes after treatment. On days 15 and 16, all animals were subjected to the
      elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then
      examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results.
      Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed
      elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the
      amygdala of stressed rats. pCREB did not differ significantly among the groups.
      Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects
      in behavioral tests and the effects may be related to CRF1R signaling in the
      amygdala. 

PMID- 27042182
TI  - Muscle Satellite Cells: Exploring the Basic Biology to Rule Them.
AB  - Adult skeletal muscle is a postmitotic tissue with an enormous capacity to
      regenerate upon injury. This is accomplished by resident stem cells, named
      satellite cells, which were identified more than 50 years ago. Since their
      discovery, many researchers have been concentrating efforts to answer questions
      about their origin and role in muscle development, the way they contribute to
      muscle regeneration, and their potential to cell-based therapies. Satellite cells
      are maintained in a quiescent state and upon requirement are activated,
      proliferating, and fusing with other cells to form or repair myofibers. In
      addition, they are able to self-renew and replenish the stem pool. Every phase of
      satellite cell activity is highly regulated and orchestrated by many molecules
      and signaling pathways; the elucidation of players and mechanisms involved in
      satellite cell biology is of extreme importance, being the first step to expose
      the crucial points that could be modulated to extract the optimal response from
      these cells in therapeutic strategies. Here, we review the basic aspects about
      satellite cells biology and briefly discuss recent findings about therapeutic
      attempts, trying to raise questions about how basic biology could provide a solid
      scaffold to more successful use of these cells in clinics. 

PMID- 27042186
TI  - Anti-Inflammatory and Antiosteoarthritis Effects of Saposhnikovia divaricata
      ethanol Extract: In Vitro and In Vivo Studies.
AB  - Saposhnikovia divaricata Schischkin has been used in traditional medicine to
      treat pain, inflammation, and arthritis. The aim of this study was to investigate
      the anti-inflammatory and antiosteoarthritis activities of Saposhnikovia
      divaricata extract (SDE). The anti-inflammatory effect of SDE was evaluated in
      vitro in lipopolysaccharide- (LPS-) treated RAW 264.7 cells. The
      antiosteoarthritic effect of SDE was investigated in an in vivo rat model of
      monosodium iodoacetate- (MIA-) induced osteoarthritis (OA) in which rats were
      treated orally with SDE (200 mg/kg) for 28 days. The effects of SDE were assessed
      in vivo by histopathological analysis and by measuring weight-bearing
      distribution, cytokine serum levels, and joint tissue inflammation-related gene
      expression. SDE showed anti-inflammatory activity by inhibiting the production of
      nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF
      alpha), and interleukin-6 (IL-6) in LPS-induced RAW 264.7 cells. In addition, SDE
      promoted recovery of hind limb weight-bearing, inhibited the production of
      proinflammatory cytokines and mediators, and protected cartilage and subchondral
      bone tissue in the OA rat model. Therefore, SDE is a potential therapeutic agent
      for OA and/or associated symptoms. 

PMID- 27042187
TI  - DNA Protection against Oxidative Damage Using the Hydroalcoholic Extract of
      Garcinia mangostana and Alpha-Mangostin.
AB  - Garcinia mangostana, popularly known as "mangosteen fruit," originates from
      Southeast Asia and came to Brazil about 80 years ago where it mainly grows in the
      states of Para and Bahia. Although mangosteen or its extracts have been used for
      ages in Asian folk medicine, data on its potential genotoxicity is missing. We,
      therefore, evaluated genotoxicity/mutagenicity of hydroethanolic mangosteen
      extract [HEGM, 10 to 640 MUg/mL] in established test assays (Comet assay,
      micronucleus test, and Salmonella/microsome test). In the Comet assay, HEGM
      exposed human leukocytes showed no DNA damage. No significant HEGM-induced
      mutation in TA98 and TA100 strains of Salmonella typhimurium (with or without
      metabolic activation) was observed and HEGM-exposed human lymphocytes had no
      increase of micronuclei. However, HEGM suggested exposure concentration-dependent
      antigenotoxic potential in leukocytes and antioxidant potential in the yeast
      Saccharomyces cerevisiae. HEGM preloading effectively protected against H2O2
      induced DNA damage in leukocytes (Comet assay). Preloading of yeast with HEGM for
      up to 4 h significantly protected the cells from lethality of chronic H2O2
      exposure, as expressed in better survival. Absence of genotoxicity and
      demonstration of an antigenotoxic and antioxidant potential suggest that HEGM or
      some substances contained in it may hold promise for pharmaceutical or
      nutraceutical application. 

PMID- 27042188
TI  - Medicinal Plants from Mexico, Central America, and the Caribbean Used as
      Immunostimulants.
AB  - A literature review was undertaken by analyzing distinguished books,
      undergraduate and postgraduate theses, and peer-reviewed scientific articles and
      by consulting worldwide accepted scientific databases, such as SCOPUS, Web of
      Science, SCIELO, Medline, and Google Scholar. Medicinal plants used as
      immunostimulants were classified into two categories: (1) plants with
      pharmacological studies and (2) plants without pharmacological research.
      Medicinal plants with pharmacological studies of their immunostimulatory
      properties were subclassified into four groups as follows: (a) plant extracts
      evaluated for in vitro effects, (b) plant extracts with documented in vivo
      effects, (c) active compounds tested on in vitro studies, and (d) active
      compounds assayed in animal models. Pharmacological studies have been conducted
      on 29 of the plants, including extracts and compounds, whereas 75 plants lack
      pharmacological studies regarding their immunostimulatory activity. Medicinal
      plants were experimentally studied in vitro (19 plants) and in vivo (8 plants). A
      total of 12 compounds isolated from medicinal plants used as immunostimulants
      have been tested using in vitro (11 compounds) and in vivo (2 compounds) assays.
      This review clearly indicates the need to perform scientific studies with
      medicinal flora from Mexico, Central America, and the Caribbean, to obtain new
      immunostimulatory agents. 

PMID- 27042189
TI  - Biological Evaluation and Docking Analysis of Daturaolone as Potential
      Cyclooxygenase Inhibitor.
AB  - This study deals with the isolation of the active constituent(s) from a
      methanolic extract of Pistacia integerrima J. L. Stewart barks and it was also
      oriented to evaluate the in vivo and in silico anti-inflammatory activity. By NMR
      and crystallography techniques, we have isolated a triterpenoid identified as
      daturaolone (compound 1). This compound showed in vivo a significant and dose
      dependent (1-30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse
      paw oedema (ED50 = 10.1 mg/kg) and on acetic acid-induced writhing responses in
      mice (ED50 = 13.8 mg/kg). In the in vivo experiments, the effect of tested
      compound was also evaluated in presence of the reference drug diclofenac (1-30
      mg/kg). Moreover, in silico analysis of receptor ligand complex shows that
      compound 1 interacts with cyclooxygenases (COXs) binding sites displaying an
      interesting interaction with COX-1. These findings suggest that compound 1
      isolated from P. integerrima possesses in vivo anti-inflammatory and
      antinociceptive potentials, which are supported in silico by an interaction with
      COXs receptors. 

PMID- 27042190
TI  - Metabolomic Analysis of Biochemical Changes in the Plasma of High-Fat Diet and
      Streptozotocin-Induced Diabetic Rats after Treatment with Isoflavones Extract of
      Radix Puerariae.
AB  - The main purpose of this study was to investigate the protective effects of total
      isoflavones from Radix Puerariae (PTIF) in diabetic rats. Diabetes was induced by
      a high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ; 40
      mg/kg). At 26 weeks onwards, PTIF 421 mg/kg was administrated to the rats once
      daily consecutively for 10 weeks. Metabolic profiling changes were analyzed by
      Ultraperformance Liquid Chromatography-Quadrupole-Exactive Orbitrap-Mass
      Spectrometry (UPLC-Q-Exactive Orbitrap-MS). The principal component discriminant
      analysis (PCA-DA), partial least-squares discriminant analysis (PLS-DA), and
      orthogonal partial least-squares discriminant analysis (OPLS-DA) were used for
      multivariate analysis. Moreover, free amino acids in serum were determined by
      high-performance liquid chromatography with fluorescence detector (HPLC-FLD).
      Additionally, oxidative stress and inflammatory cytokines were evaluated. Eleven
      potential metabolite biomarkers, which are mainly related to the coagulation,
      lipid metabolism, and amino acid metabolism, have been identified. PCA-DA scores
      plots indicated that biochemical changes in diabetic rats were gradually restored
      to normal after administration of PTIF. Furthermore, the levels of BCAAs,
      glutamate, arginine, and tyrosine were significantly increased in diabetic rats.
      Treatment with PTIF could regulate the disturbed amino acid metabolism.
      Consequently, PTIF has great therapeutic potential in the treatment of DM by
      improving metabolism disorders and inhibiting oxidative damage. 

PMID- 27042191
TI  - Health-Promoting Properties of Eucommia ulmoides: A Review.
AB  - Eucommia ulmoides (EU) (also known as "Du Zhong" in Chinese language) is a plant
      containing various kinds of chemical constituents such as lignans, iridoids,
      phenolics, steroids, flavonoids, and other compounds. These constituents of EU
      possess various medicinal properties and have been used in Chinese Traditional
      Medicine (TCM) as a folk drink and functional food for several thousand years. EU
      has several pharmacological properties such as antioxidant, anti-inflammatory,
      antiallergic, antimicrobial, anticancer, antiaging, cardioprotective, and
      neuroprotective properties. Hence, it has been widely used solely or in
      combination with other compounds to treat cardiovascular and cerebrovascular
      diseases, sexual dysfunction, cancer, metabolic syndrome, and neurological
      diseases. This review paper summarizes the various active ingredients contained
      in EU and their health-promoting properties, thus serving as a reference material
      for the application of EU. 

PMID- 27042192
TI  - Effects of Wutou Decoction on DNA Methylation and Histone Modifications in Rats
      with Collagen-Induced Arthritis.
AB  - Background. Wutou decoction (WTD) has been wildly applied in the treatment of
      rheumatoid arthritis and experimental arthritis in rats for many years.
      Epigenetic deregulation is associated with the aetiology of rheumatoid arthritis;
      however, the effects of WTD on epigenetic changes are unclear. This study is set
      to explore the effects of WTD on DNA methylation and histone modifications in
      rats with collagen-induced arthritis (CIA). Methods. The CIA model was
      established by the stimulation of collagen and adjuvant. The knee synovium was
      stained with hematoxylin and eosin. The DNA methyltransferase 1 (DNMT1) and
      methylated CpG binding domain 2 (MBD2) expression of peripheral blood mononuclear
      cells (PBMCs) were determined by Real-Time PCR. The global DNA histone H3-K4/H3
      K27 methylation and total histones H3 and H4 acetylation of PBMCs were detected.
      Results. Our data demonstrated that the DNMT1 mRNA expression was significantly
      lowered in group WTD compared to that in group CIA (P < 0.05). The DNA
      methylation level was significantly reduced in group WTD compared to that in
      group CIA (P < 0.05). Moreover, H3 acetylation of PBMCs was overexpressed in WTD
      compared with CIA (P < 0.05). Conclusions. WTD may modulate DNA methylation and
      histone modifications, functioning as anti-inflammatory potential. 

PMID- 27042193
TI  - Incidence and risk factors for liver enzymes elevations in highly treatment
      experienced patients switching from enfuvirtide to raltegravir: a sub-study of
      the ANRS-138 EASIER trial.
AB  - BACKGROUND: In the ANRS EASIER trial where treatment-experienced patients
      switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of
      transaminase elevation was reported in the RAL arm. METHODS: We compared the
      incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among
      patients randomized to the maintenance ENF arm or the switch RAL arm up to W24.
      We also assessed the overall incidence of LEE over the 48-week duration of the
      trial and baseline risk factors for grade 2 or more alanine aminotransferase
      (ALT) elevation using univariate and multivariate analyses. RESULTS: During the
      first 24 weeks, 6/84 (7.1 %) and 2/85 patients (2.4 %) presented with ALT
      elevation of grade 2 or more in the RAL and ENF arms, respectively (p = 0.21).
      Grade 2 or more gammaGT and ALP elevations were seen in 18 and 11 % (p = 0.35),
      and 5 and 1 % (p = 0.14) of patients in the RAL and ENF arms, respectively. The
      48-week incidence of grade 2 or more LEE was 11.6 per 100-pts-years for ALT, 24.5
      per 100-pts-years for gamma-GT and 4.5 per 100-pts-years for ALP, respectively.
      In the multivariate analysis, tipranavir/ritonavir use (OR 3.66; 95 % CI [1.20
      11.1], p = 0.022) and elevated ALT at baseline (OR 10.3; 95 % CI [2.67-39.6], p <
      10(-3)) were significantly associated with a grade 2 or more ALT elevation during
      follow-up. CONCLUSION: The incidence of LEE was relatively high in these highly
      treatment-experienced patients switching to a RAL-based regimen. Both
      tipranavir/ritonavir use and high baseline ALT levels were associated with an
      increased risk of ALT. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00454337.

PMID- 27042194
TI  - Relationship between the lesion location of acute ischemic stroke and early
      depressive symptoms in Japanese patients.
AB  - BACKGROUND: Approximately one-third of stroke survivors suffer from post-stroke
      depression (PSD) in the acute or chronic stages. The presence of PSD in the acute
      stage after stroke is reportedly associated with poor patient prognosis;
      therefore, early recognition and treatment of PSD may alleviate these
      consequences. The aim of the current study was to examine the relationship
      between the lesion location and the presence of early depressive symptoms after
      acute ischemic stroke in Japanese patients. METHODS: Our study included 421
      patients who suffered from acute ischemic stroke. On the day of admission, the
      lesion location was determined using magnetic resonance imaging (MRI). Stroke
      severity was measured on the seventh day of hospitalization withat the National
      Institutes of Health Stroke Scale (NIHSS). On the tenth day of hospitalization,
      depressive symptoms were measured and functional assessments were performed with
      the Japan Stroke Scale (Depression Scale) (JSS-D) and functional independence
      measure (FIM), respectively. RESULTS: A total of 71 subjects (16.9 %) were
      diagnosed with depression. According to the multiple logistic regression
      analysis, the infarcts located at frontal and temporal lobes were found to be a
      significant independent risk factor of early depressive symptoms in the acute
      stage of stroke. CONCLUSIONS: Patients suffering from acute ischemic stroke,
      particularly in the frontal and temporal lobes, should be carefully assessed to
      detect and treat early depressive symptoms; such treatment may improve patient
      outcomes.

PMID- 27042195
TI  - Peer mentorship program on HIV/AIDS knowledge, beliefs, and prevention attitudes
      among orphaned adolescents: an evidence based practice.
AB  - Adolescents and young adults in sub-Saharan Africa (SSA) are particularly
      vulnerable to human immunodeficiency virus (HIV) and acquired immune deficiency
      syndrome (AIDS) infection. Adolescents orphaned as a direct result of HIV/AIDS
      are at an elevated risk of acquiring HIV/AIDS and other sexually transmitted
      infections. However, limited empirical evidence exists on HIV knowledge and
      prevention programs, especially those designed to address HIV information gaps
      among adolescents. This study evaluates the effect of a peer mentorship program
      provided in addition to other supportive services on HIV/AIDS knowledge, beliefs,
      and prevention attitudes, among school-going orphaned adolescents in southern
      Uganda. We utilize data from the Bridges to the Future Study, a 5-year
      longitudinal randomized experimental study funded by the National Institute of
      Child Health and Human Development. Out of the 1410 adolescents enrolled in the
      study (average age = 12.7 at study initiation), 855 of them participated in a
      nine-session, curriculum based peer mentorship program. We analyzed data
      collected at baseline and 12-months post intervention initiation. The results
      from bivariate and regression analysis indicate that, controlling for
      socioeconomic characteristics, adolescents who participated in a peer mentorship
      program were more likely than non-participants to report increased scores on
      HIV/AIDS knowledge(b = .86, 95%CI = .47 - 1.3, p <= .001); better scores on
      desired HIV/AIDS-related beliefs (b = .29, 95%CI = .06 - .52, p <= .01); and
      better scores on HIV/AIDS prevention attitudes (b = .76, 95%CI = .16 - 1.4, p <=
      .01). Overall, the study findings point to the potential role a of peer
      mentorship program in promoting the much-desired HIV/AIDS knowledge, beliefs, and
      prevention attitudes among orphaned adolescents. Future programs and policies
      that support AIDS-orphaned adolescents in sub-Saharan Africa should consider
      incorporating peer mentoring programs that provide correct, age, and culturally
      appropriate HIV information to help protect orphaned adolescents and reduce the
      risk of HIV infections.

PMID- 27042196
TI  - Complex young lives: a collective qualitative case study analysis of young
      fatherhood and breastfeeding.
AB  - BACKGROUND: Of all births in Australia, 10 % are to young fathers aged less than
      24 years. How young fathers experience any breastfeeding and how this is shaped
      by their social context is poorly understood. Our aim is to increase
      understanding of the lived experience of young fathers (aged less than 24 years)
      and to explore the way they speak about breastfeeding in the context of their
      lives and parenting. METHODS: This collective case study analysis uses
      qualitative data from interviews and focus groups with young fathers (aged less
      than 24 years) and community support staff. The research was undertaken in
      Tasmania, Australia, March to December 2013. RESULTS: Young fathers in our study
      had complex social and emotional circumstances that meant breastfeeding was not a
      high priority despite them valuing the health benefits of breastfeeding for their
      babies. If supported by peers and their community they appear to have a more
      positive parenting experience. CONCLUSION: Breastfeeding although understood by
      the young fathers in our study as healthy and desirable is not a priority in
      their lives. Learning to be a parent and support their partners to breastfeed may
      be more effectively gained through mentoring and father-to-father localized
      community based support services.

PMID- 27042197
TI  - New insights into posttranslational modifications of Hippo pathway in
      carcinogenesis and therapeutics.
AB  - PTMs (posttranslational modifications) such as ubiquitylation, sumoylation,
      acetylation and protein methylation are pivotal modifiers that determine the
      activation, deactivation or subcellular localization of signaling proteins,
      facilitating the initiation, amplification and transduction of signaling.
      Accumulating evidence suggest that several key signaling molecules in Hippo
      signaling pathway are tightly regulated by various types of PTMs. Malfunction of
      these critical signaling modules such as YAP/TAZ, MAT1/2 and LATS1/2 due to
      deregulated PTMs has been linked to a variety of human diseases such as cancer.
      In this review article, we summarized the current understanding of the impact of
      PTMs in regulating Hippo signaling pathway and further discussed the potential
      therapeutic intervention from the view of PTMs and Hippo pathway. 

PMID- 27042199
TI  - Seasonality Impact on the Transmission Dynamics of Tuberculosis.
AB  - The statistical data of monthly pulmonary tuberculosis (TB) incidence cases from
      January 2004 to December 2012 show the seasonality fluctuations in Shaanxi of
      China. A seasonality TB epidemic model with periodic varying contact rate,
      reactivation rate, and disease-induced death rate is proposed to explore the
      impact of seasonality on the transmission dynamics of TB. Simulations show that
      the basic reproduction number of time-averaged autonomous systems may
      underestimate or overestimate infection risks in some cases, which may be up to
      the value of period. The basic reproduction number of the seasonality model is
      appropriately given, which determines the extinction and uniform persistence of
      TB disease. If it is less than one, then the disease-free equilibrium is globally
      asymptotically stable; if it is greater than one, the system at least has a
      positive periodic solution and the disease will persist. Moreover, numerical
      simulations demonstrate these theorem results. 

PMID- 27042198
TI  - Cul3-KLHL20 ubiquitin ligase: physiological functions, stress responses, and
      disease implications.
AB  - Cullin-RING ubiquitin ligases are the largest Ubiquitin ligase family in
      eukaryotes and are multi-protein complexes. In these complexes, the Cullin
      protein serves as a scaffold to connect two functional modules of the ligases,
      the catalytic subunit and substrate-binding subunit. KLHL20 is a substrate
      binding subunit of Cullin3 (Cul3) ubiquitin ligase. Recent studies have
      identified a number of substrates of KLHL20-based ubiquitin ligase. Through
      ubiquitination of these substrates, KLHL20 elicits diverse cellular functions,
      some of which are associated with human diseases. Furthermore, the functions,
      subcellular localizations, and expression of KLHL20 are regulated by several
      physiological and stressed signals, which allow KLHL20 to preferentially act on
      certain substrates to response to these signals. Here, we provide a summary of
      the functions and regulations of KLHL20 in several physiological processes and
      stress responses and its disease implications. 

PMID- 27042200
TI  - Computer Aided Detection System for Prediction of the Malaise during
      Hemodialysis.
AB  - Monitoring of dialysis sessions is crucial as different stress factors can yield
      suffering or critical situations. Specialized personnel is usually required for
      the administration of this medical treatment; nevertheless, subjects whose
      clinical status can be considered stable require different monitoring strategies
      when compared with subjects with critical clinical conditions. In this case
      domiciliary treatment or monitoring can substantially improve the quality of life
      of patients undergoing dialysis. In this work, we present a Computer Aided
      Detection (CAD) system for the telemonitoring of patients' clinical parameters.
      The CAD was mainly designed to predict the insurgence of critical events; it
      consisted of two Random Forest (RF) classifiers: the first one (RF1) predicting
      the onset of any malaise one hour after the treatment start and the second one
      (RF2) again two hours later. The developed system shows an accurate
      classification performance in terms of both sensitivity and specificity. The
      specificity in the identification of nonsymptomatic sessions and the sensitivity
      in the identification of symptomatic sessions for RF2 are equal to 86.60% and
      71.40%, respectively, thus suggesting the CAD as an effective tool to support
      expert nephrologists in telemonitoring the patients. 

PMID- 27042203
TI  - A flexible tool to plot a genomic map for single nucleotide polymorphisms.
AB  - BACKGROUND: Most genetic association studies use single-nucleotide polymorphisms
      (SNPs) as the research targets. However, resources to visualize the genomic map
      of candidate SNPs in a programming manner are limited. We have previously created
      an R package, mapsnp v0.1, to plot the genomic map for a panel of SNPs within a
      genomic region of interest. It failed to work under the latest version of Gviz
      package. RESULTS: We updated the mapsnp package to keep up with the latest
      package environment and improved its functionality by adding more parameters to
      fine tune plotting outputs. CONCLUSIONS: The mapsnp package is a flexible
      software to visualize genomic map for SNPs, involving the relative chromosome
      location and the transcripts in the region.

PMID- 27042202
TI  - Apoptosis-inducing effects of jujube (Zao) seed extracts on human Jurkat leukemia
      T cells.
AB  - BACKGROUND: Jujube (Zao) seeds exhibited anticancer effects and used in Chinese
      medicine for many years. This study aims to investigate the apoptosis-inducing
      effects of seed extracts from eight different cultivated species ('Apple',
      'Bombay', 'Jumbo', 'Kaew', 'Nomsod', 'Rianthong', 'Samros', and 'Taiwan') on
      human Jurkat leukemia T cells. METHODS: We evaluated the effects of seed extracts
      from eight jujube cultivated species on human Jurkat leukemia T cells. The crude
      seed extracts were prepared sequentially by using water, 95 % ethanol,
      dichloromethane, ethyl acetate, chloroform or hexane. The antiproliferative
      effects of the jujube seed extracts relative to that of melphalan were evaluated
      by neutral red assays. Apoptotic cell death induced by the ethanolic extracts at
      1 * IC50 and 2 * IC50 concentrations was demonstrated by DAPI staining, gel
      electrophoresis, flow cytometry with Annexin V/propidium iodide staining, and
      caspase-3, -8, and -9 enzyme activities. RESULTS: Ethanolic extracts of 'Taiwan',
      'Jumbo', 'Nomsod', 'Rianthong', 'Samros', and 'Bombay', significantly inhibited
      the proliferation of Jurkat cells compared with untreated cells (all P < 0.001),
      while the extracts of 'Kaew' and 'Apple' were inactive. The six active extracts
      preferentially induced apoptotic cell death in a concentration-dependent manner
      with DNA fragmentation (2 * IC50). Increased caspase-3 activity was detected
      after treatment with the six extracts. The 'Taiwan', 'Nomsod', 'Jumbo', and
      'Rianthong' extracts (2 * IC50) induced both the extrinsic and intrinsic
      apoptosis pathways by increasing caspase-8 and caspase-9 activity, respectively.
      Alkaloids (Dragendorff's method) and reducing sugars (Fehling's test) were mainly
      identified in the apoptosis-inducing extracts. CONCLUSIONS: The tested of six
      active extracts ('Taiwan', 'Jumbo', 'Nomsod', 'Rianthong', 'Samros' and 'Bombay')
      contained alkaloids or reducing sugars, and induced caspase-dependent apoptosis
      in human Jurkat leukemia T cells.

PMID- 27042204
TI  - Equilibria in cobalt(II)-amino acid-imidazole system under oxygen-free
      conditions: effect of side groups on mixed-ligand systems with selected L-alpha
      amino acids.
AB  - BACKGROUND: Heteroligand Co(II) complexes involving imidazole and selected bio
      relevant L-alpha-amino acids of four different groups (aspartic acid, lysine,
      histidine and asparagine) were formed by using a polymeric, pseudo-tetrahedral,
      semi-conductive Co(II) complex with imidazole-[Co(imid)2]n as starting material.
      The coordination mode in the heteroligand complexes was unified to one imidazole
      in the axial position and one or two amino acid moieties in the appropriate
      remaining positions. The corresponding equilibrium models in aqueous solutions
      were fully correlated with the mass and charge balance equations, without any of
      the simplified assumptions used in earlier studies. Precise knowledge of
      equilibria under oxygen-free conditions would enable evaluation of the reversible
      oxygen uptake in the same Co(II)-amino acid-imidazole systems, which are known
      models of artificial blood-substituting agents. RESULTS: Heteroligand complexes
      were formed as a result of proton exchange between the two imidazole molecules
      found in the [Co(imid)2]n polymer and two functional groups of the amino acid.
      Potentiometric titrations were confirmed by UV/Vis titrations of the respective
      combinations of amino acids and Co-imidazole. Formation of MLL' and ML2L' species
      was confirmed for asparagine and aspartic acid. For the two remaining amino
      acids, the accepted equilibrium models had to include species protonated at the
      side-chain amine group (as in the case of lysine: MLL'H, ML2L'H2, ML2L'H) or at
      the imidazole N1 (as in the case of histidine: MLL'H and two isomeric forms of
      ML2L'). Moreover, the Deltalog10 beta, log10 beta stat, Deltalog10 K, and log10 X
      parameters were used to compare the stability of the heteroligand complexes with
      their respective binary species. The large differences between the constant for
      the mixed-ligand complex and the constant based on statistical data Deltalog10
      beta indicate that the heteroligand species are more stable than the binary ones.
      The parameter Deltalog10 K, which describes the influence of the bonded primary
      ligand in the binary complex Co(II)(Himid) towards an incoming secondary ligand
      (L) forming a heteroligand complex, was negative for all the Amac ligands (except
      for histidine, which shows stacking interactions). This indicates that the mixed
      ligand systems are less stable than the binary complexes with one molecule of
      imidazole or one molecule of amino acid, in contrast to Deltalog10 beta, which
      deals with binary complexes Co(II)(Himid)2 and Co(II)(AmacH-1)2 containing two
      ligand molecules. The high positive values of the log10 X disproportionation
      parameter were in good agreement with the results of the Deltalog10 beta
      calculations mentioned above. CONCLUSION: The mixed-ligand MLL'-type complexes
      are formed at pH values above 4-6 (depending on the amino acid used), however,
      the so-called "active" ML2L'-type complexes, present in the equilibrium mixture
      and known to be capable of reversible dioxygen uptake, attain maximum share at a
      pH around nine. For all the amino acids involved, the greater the excess of amino
      acid, the lower the pH where the given heteroligand complex attains maximum
      share. The results of our equilibrium studies make it possible to evaluate the
      oxygenation constants in full accordance with the distribution of species in
      solution. Such calculations are needed to drive further investigations of
      artificial blood-substituting systems.

PMID- 27042205
TI  - Autoclave mediated one-pot-one-minute synthesis of AgNPs and Au-Ag nanocomposite
      from Melia azedarach bark extract with antimicrobial activity against food
      pathogens.
AB  - BACKGROUND: The increasing use of nanoparticles and nanocomposite in
      pharmaceutical and processed food industry have increased the demand for nontoxic
      and inert metallic nanostructures. Chemical and physical method of synthesis of
      nanostructures is most popular in industrial production, despite the fact that
      these methods are labor intensive and/or generate toxic effluents. There has been
      an increasing demand for rapid, ecofriendly and relatively cheaper synthesis of
      nanostructures. METHODS: Here, we propose a strategy, for one-minute green
      synthesis of AgNPs and a one-pot one-minute green synthesis of Au-Ag
      nanocomposite, using Melia azedarach bark aqueous extract as reducing agent. The
      hydrothermal mechanism of the autoclave technology has been successfully used in
      this study to accelerate the nucleation and growth of nano-crystals. RESULTS: The
      study also presents high antimicrobial potential of the synthesized nano
      solutions against common food and water born pathogens. The multistep
      characterization and analysis of the synthesized nanomaterial samples, using UV
      visible spectroscopy, ICP-MS, FT-IR, EDX, XRD, HR-TEM and FE-SEM, also reveal the
      reaction dynamics of AgNO3, AuCl3 and plant extract in synthesis of the
      nanoparticles and nanocomposite. CONCLUSIONS: The antimicrobial effectiveness of
      the synthesized Au-Ag nanocomposite, with high gold to silver ratio, reduces the
      dependency on the AgNPs, which is considered to be environmentally more toxic
      than the gold counterpart. We hope that this new strategy will change the present
      course of green synthesis. The rapidity of synthesis will also help in industrial
      scale green production of nanostructures using Melia azedarach.

PMID- 27042206
TI  - Enhanced preferential cytotoxicity through surface modification: synthesis,
      characterization and comparative in vitro evaluation of TritonX-100 modified and
      unmodified zinc oxide nanoparticles in human breast cancer cell (MDA-MB-231).
AB  - BACKGROUND: Nanoparticles (NPs) are receiving increasing interest in biomedical
      research owing to their comparable size with biomolecules, novel properties and
      easy surface engineering for targeted therapy, drug delivery and selective
      treatment making them a better substituent against traditional therapeutic
      agents. ZnO NPs, despite other applications, also show selective anticancer
      property which makes it good option over other metal oxide NPs. ZnO NPs were
      synthesized by chemical precipitation technique, and then surface modified using
      Triton X-100. Comparative study of cytotoxicity of these modified and unmodified
      NPs on breast cancer cell line (MDA-MB-231) and normal cell line (NIH 3T3) were
      carried out. RESULTS: ZnO NPsof average size 18.67 +/- 2.2 nm and Triton-X
      modified ZnO NPs of size 13.45 +/- 1.42 nm were synthesized and successful
      characterization of synthesized NPs was done by Fourier transform infrared
      spectroscopy (FT-IR), X-Ray diffraction (XRD), transmission electron microscopy
      (TEM) analysis. Surface modification of NPs was proved by FT-IR analysis whereas
      structure and size by XRD analysis. Morphological analysis was done by TEM. Cell
      viability assay showed concentration dependent cytotoxicity of ZnO NPs in breast
      cancer cell line (MDA-MB-231) whereas no positive correlation was found between
      cytotoxicity and increasing concentration of stress in normal cell line (NIH 3T3)
      within given concentration range. Half maximum effective concentration (EC50)
      value for ZnO NPs was found to be 38.44 ug/ml and that of modified ZnO NPs to be
      55.24 ug/ml for MDA-MB-231. Crystal violet (CV) staining image showed reduction
      in number of viable cells in NPs treated cell lines further supporting this
      result. DNA fragmentation assay showed fragmented bands indicating that the
      mechanism of cytotoxicity is through apoptosis. CONCLUSIONS: Although use of
      surfactant decreases particle size, toxicity of modified ZnO NPs were still less
      than unmodified NPs on MDA-MB-231 contributed by biocompatible surface coating.
      Both samples show significantly less toxicity towards NIH 3T3 in concentration
      independent manner. But use of Triton-X, a biocompatible polymer, enhances this
      preferentiality effect. Since therapeutic significance should be analyzed through
      its comparative effect on both normal and cancer cells, possible application of
      biocompatible polymer modified nanoparticles as therapeutic agent holds better
      promise.Graphical abstractSurface coating, characterization and comparative in
      vitro cytotoxicity study on MDA-MB 231 and NIH 3T3 of ZnO NPs showing enhanced
      preferentiality by biocompatible surface modification.

PMID- 27042207
TI  - Regioselectivity of 1,3-dipolar cycloadditions and antimicrobial activity of
      isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-diones, pyrazolo[3,4-d]pyridazines and
      pyrazolo[1,5-a]pyrimidines.
AB  - BACKGROUND: Isoxazoles exhibit interesting biological activities, and the 1,3
      dipolar cycloaddition(13DC) reactions play an important role in both mechanistic
      and synthetic organic chemistry. Pyrazoles and annulated pyrazoles exhibit some
      diverse biological activities. They are used as antipyretic, analgesic drugs,
      tranquilizing, and herbicidal agents. Pyrazoles are also used extensively as
      useful synthons in organic synthesis. Pyrazolo[3,4-d]pyridazines showed good
      antimicrobial, anti-inflammatory and analgesic activities. Several oximes are
      found to be hyperglycemic, anti-neoplastic, anti-inflammatory, anti-leishmanial
      and VEGFR-2 kinase inhibitors. RESULTS: The present work describes an efficient
      synthesis protocol and molecular orbital calculations of isoxazoline and
      pyrrolo[3,4-d]isoxazole-4,6-dione derivatives from the reaction of hydroximoyl
      chloride with acrylonitrile, acrylamide, and N-arylmalemides. In addition,
      pyrazoles and pyrazolo[3,4-d]pyridazines are obtained via the reaction of 3
      (dimethylamino)-1-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-ene-1-one with
      hydrazonoyl halides. Pyrazolo[1,5-a]pyrimidines were derived from condensation of
      either Sodium Salt of 3-Hydroxy-1-(2,4-dimethylthiazol-5-yl)prop-2-en-1-one (10)
      or 3-(dimethylamino)-1-(2,4-dimethyl)(1,3-thiazol-5-yl)prop-2-en-1-one (11) with
      aiminopyrozoles. A comparative study of the biological activity of the
      synthesized compounds with ampicillin and tetracycline is compiled in Table 3.
      Generally, all synthesized compounds showed an adequate inhibitory efficiency of
      growth of gram-positive and gram-negative bacteria. Structures of the newly
      synthesized compounds were elucidated by elemental analysis, spectral data and a
      computational study. CONCLUSIONS: In summary, new and efficient synthetic routes
      of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-dione derivatives, pyrazoles,
      pyrazolo[3,4-d]pyridazines and pyrazolo[1,5-a]pyrimidines have been achieved and
      the biological activity has been investigated.Graphical abstractNew and efficient
      synthetic routes of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-dione derivatives,
      pyrazolo[3,4-d]pyridazines and pyrazolo [1,5-a] pyrimidines.

PMID- 27042208
TI  - A qualitative exploration of a family self-help mental health program in El
      Salvador.
AB  - BACKGROUND: There is a significant gap in our knowledge regarding community-based
      self-help groups and their benefits for persons living with mental conditions and
      their family caregivers in low and middle income countries. This study describes
      a such a program in El Salvador and explores participants' perceptions of program
      effectiveness and benefits. CASE DESCRIPTION: The Family Education, Support and
      Empowerment Program is a multi-component program in the capital that is
      facilitated by nonprofit professionals but carried out primarily by volunteers. A
      focus group methodology to build evaluation and research capacity in the
      organization was used. The study consisted of a questionnaire completed by
      participants individually, followed by two focus group sessions with the same ten
      people. RESULTS: The study found perceptions of multiple benefits across social,
      functional, and economic dimensions and a variety of achievements at
      organizational and national levels. DISCUSSION: This study identified a family
      self-help program in El Salvador as a potentially highly beneficial program for
      its participants. This appears to be the first study to explore benefits across
      micro, mezzo and macro social levels and to include discussion of more diverse
      potential benefits such as individual and organizational social capital,
      leadership, and advocacy. These factors should be explored in future quantitative
      studies to help determine the relative importance and usefulness of such programs
      in meeting World Health Organization goals for access to mental health treatment
      and quality community-based services.

PMID- 27042209
TI  - Microbial synthesis of propane by engineering valine pathway and aldehyde
      deformylating oxygenase.
AB  - BACKGROUND: Propane, a major component of liquid petroleum gas (LPG) derived from
      fossil fuels, has widespread applications in vehicles, cooking, and ambient
      heating. Given the concerns about fossil fuel depletion and carbon emission,
      exploiting alternative and renewable source of propane have become attractive. In
      this study, we report the construction of a novel propane biosynthetic pathway in
      Escherichia coli. RESULTS: We constructed an aldehyde reductases (ALR)-deprived
      E. coli strain BW25113(DE3) Delta13 via genetic engineering, which produced
      sufficient isobutyraldehyde precursors and finally achieved de novo synthesis of
      propane (91 MUg/L) by assembling the engineered valine pathway and cyanobacterial
      aldehyde-deformylating oxygenase (ADO). Additionally, after extensive screening
      of ADO mutants generated by engineering the active center to accommodate branched
      chain isobutyraldehyde, we identified two ADO mutants (I127G, I127G/A48G) which
      exhibited higher catalytic activity for isobutyraldehyde and improved propane
      productivity by three times (267 MUg/L). CONCLUSIONS: The propane biosynthetic
      pathway constructed here through the engineered valine pathway can produce
      abundant isobutyraldehyde for ADO and overcome the low availability of precursors
      in propane production. Furthermore, the rational design aiming at the ADO active
      center illustrates the plasticity and catalytic potential of ADO. These results
      together highlight the potential for developing a microbial biomanufacturing
      platform for propane.

PMID- 27042210
TI  - Direct bioconversion of brown algae into ethanol by thermophilic bacterium
      Defluviitalea phaphyphila.
AB  - BACKGROUND: Brown algae are promising feedstocks for biofuel production with
      inherent advantages of no structural lignin, high growth rate, and no competition
      for land and fresh water. However, it is difficult for one microorganism to
      convert all components of brown algae with different oxidoreduction potentials to
      ethanol. Defluviitalea phaphyphila Alg1 is the first characterized thermophilic
      bacterium capable of direct utilization of brown algae. RESULTS: Defluviitalea
      phaphyphila Alg1 can simultaneously utilize mannitol, glucose, and alginate to
      produce ethanol, and high ethanol yields of 0.47 g/g-mannitol, 0.44 g/g-glucose,
      and 0.3 g/g-alginate were obtained. A rational redox balance system under
      obligate anaerobic condition in fermenting brown algae was revealed in D.
      phaphyphila Alg1 through genome and redox analysis. The excess reducing
      equivalents produced from mannitol metabolism were equilibrated by oxidizing
      forces from alginate assimilation. Furthermore, D. phaphyphila Alg1 can directly
      utilize unpretreated kelp powder, and 10 g/L of ethanol was accumulated within 72
      h with an ethanol yield of 0.25 g/g-kelp. Microscopic observation further
      demonstrated the deconstruction process of brown algae cell by D. phaphyphila
      Alg1. CONCLUSIONS: The integrated biomass deconstruction system of D. phaphyphila
      Alg1, as well as its high ethanol yield, provided us an excellent alternative for
      brown algae bioconversion at elevated temperature.

PMID- 27042211
TI  - Production of medium-chain fatty acids and higher alcohols by a synthetic co
      culture grown on carbon monoxide or syngas.
AB  - BACKGROUND: Synthesis gas, a mixture of CO, H2, and CO2, is a promising renewable
      feedstock for bio-based production of organic chemicals. Production of medium
      chain fatty acids can be performed via chain elongation, utilizing acetate and
      ethanol as main substrates. Acetate and ethanol are main products of syngas
      fermentation by acetogens. Therefore, syngas can be indirectly used as a
      substrate for the chain elongation process. RESULTS: Here, we report the
      establishment of a synthetic co-culture consisting of Clostridium autoethanogenum
      and Clostridium kluyveri. Together, these bacteria are capable of converting CO
      and syngas to a mixture of C4 and C6 fatty acids and their respective alcohols.
      The co-culture is able to grow using solely CO or syngas as a substrate, and
      presence of acetate significantly stimulated production rates. The co-culture
      produced butyrate and caproate at a rate of 8.5 +/- 1.1 and 2.5 +/- 0.63
      mmol/l/day, respectively. Butanol and hexanol were produced at a rate of 3.5 +/-
      0.69 and 2.0 +/- 0.46 mmol/l/day, respectively. The pH was found to be a major
      factor during cultivation, influencing the growth performance of the separate
      strains and caproate toxicity. CONCLUSION: This co-culture poses an alternative
      way to produce medium-chain fatty acids and higher alcohols from carbon monoxide
      or syngas and the process can be regarded as an integration of syngas
      fermentation and chain elongation in one growth vessel.

PMID- 27042212
TI  - Microbial network for waste activated sludge cascade utilization in an integrated
      system of microbial electrolysis and anaerobic fermentation.
AB  - BACKGROUND: Bioelectrochemical systems have been considered a promising novel
      technology that shows an enhanced energy recovery, as well as generation of value
      added products. A number of recent studies suggested that an enhancement of
      carbon conversion and biogas production can be achieved in an integrated system
      of microbial electrolysis cell (MEC) and anaerobic digestion (AD) for waste
      activated sludge (WAS). Microbial communities in integrated system would build a
      thorough energetic and metabolic interaction network regarding fermentation
      communities and electrode respiring communities. The characterization of
      integrated community structure and community shifts is not well understood,
      however, it starts to attract interest of scientists and engineers. RESULTS: In
      the present work, energy recovery and WAS conversion are comprehensively affected
      by typical pretreated biosolid characteristics. We investigated the interaction
      of fermentation communities and electrode respiring communities in an integrated
      system of WAS fermentation and MEC for hydrogen recovery. A high energy recovery
      was achieved in the MECs feeding WAS fermentation liquid through alkaline
      pretreatment. Some anaerobes belonging to Firmicutes (Acetoanaerobium,
      Acetobacterium, and Fusibacter) showed synergistic relationship with
      exoelectrogens in the degradation of complex organic matter or recycling of MEC
      products (H2). High protein and polysaccharide but low fatty acid content led to
      the dominance of Proteiniclasticum and Parabacteroides, which showed a delayed
      contribution to the extracellular electron transport leading to a slow cascade
      utilization of WAS. CONCLUSIONS: Efficient pretreatment could supply more short
      chain fatty acids and higher conductivities in the fermentative liquid, which
      facilitated mass transfer in anodic biofilm. The overall performance of WAS
      cascade utilization was substantially related to the microbial community
      structures, which in turn depended on the initial pretreatment to enhance WAS
      fermentation. It is worth noting that species in AD and MEC communities are able
      to build complex networks of interaction, which have not been sufficiently
      studied so far. It is therefore important to understand how choosing operational
      parameters can influence reactor performances. The current study highlights the
      interaction of fermentative bacteria and exoelectrogens in the integrated system.

PMID- 27042213
TI  - Differential effects of hyaluronan synthase 3 deficiency after acute vs chronic
      liver injury in mice.
AB  - BACKGROUND: Hyaluronan (HA) is a ubiquitous extracellular matrix (ECM)
      glycosaminoglycan synthesized by three different enzymes, hyaluronan synthase
      (HAS)1, 2, and 3. HA synthesis mediated by HAS3 promotes inflammation and is
      pathogenic in animal models of human lung and intestinal disease. Liver fibrosis
      is a common endpoint to chronic liver injury and inflammation for which there is
      no cure. Although plasma HA is a commonly used biomarker for liver disease, if
      and how HA contributes to disease pathogenesis remains unclear. Here, we tested
      the hypothesis that HA synthesized by HAS3 enhances inflammation and fibrosis. To
      test this hypothesis, we exposed wild-type or Has3-/- mice to carbon
      tetrachloride (CCl4) once (acute) or ten (chronic) times. RESULTS: HAS3-deficient
      mice exhibited increased hepatic injury and inflammatory chemokine production 48
      h after acute CCl4; this was associated with a threefold reduction in plasma HA
      levels and alterations in the proportions of specific molecular weight HA polymer
      pools. Hepatic accumulation of fibrosis-associated transcripts was also greater
      in livers from HAS3-deficient mice compared to controls after acute CCl4
      exposure. Surprisingly, fibrosis was not different between genotypes. Hepatic
      matrix metalloproteinase (MMP)13 mRNA and MMP13 activity was greater in livers
      from Has3-null mice after chronic CCl4; this was prevented by a MMP13-specific
      inhibitor. Collectively, these data suggest that Has3, or more likely HA produced
      by HAS3, limits hepatic inflammation after acute injury and attenuates MMP13
      mediated matrix metabolism after chronic injury. CONCLUSIONS: These data suggest
      that HA should be investigated further as a novel therapeutic target for acute
      and chronic liver disease.

PMID- 27042214
TI  - Evolutionary triangulation: informing genetic association studies with
      evolutionary evidence.
AB  - Genetic studies of human diseases have identified many variants associated with
      pathogenesis and severity. However, most studies have used only statistical
      association to assess putative relationships to disease, and ignored other
      factors for evaluation. For example, evolution is a factor that has shaped
      disease risk, changing allele frequencies as human populations migrated into and
      inhabited new environments. Since many common variants differ among populations
      in frequency, as does disease prevalence, we hypothesized that patterns of
      disease and population structure, taken together, will inform association
      studies. Thus, the population distributions of allelic risk variants should
      reflect the distributions of their associated diseases. Evolutionary
      Triangulation (ET) exploits this evolutionary differentiation by comparing
      population structure among three populations with variable patterns of disease
      prevalence. By selecting populations based on patterns where two have similar
      rates of disease that differ substantially from a third, we performed a proof of
      principle analysis for this method. We examined three disease phenotypes, lactase
      persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase
      persistence, a phenotype with a simple genetic architecture, ET identifies the
      key gene, lactase. For melanoma, ET identifies several genes associated with this
      disease and/or phenotypes related to it, such as skin color genes. ET was less
      obviously successful for Type 2 diabetes mellitus, perhaps because of the small
      effect sizes in known risk loci and recent environmental changes that have
      altered disease risk. Alternatively, ET may have revealed new genes involved in
      conferring disease risk for diabetes that did not meet nominal GWAS significance
      thresholds. We also compared ET to another method used to filter for phenotype
      associated genes, population branch statistic (PBS), and show that ET performs
      better in identifying genes known to associate with diseases appropriately
      distributed among populations. Our results indicate that ET can filter
      association results to improve our ability to discover disease loci. 

PMID- 27042215
TI  - Supercell program: a combinatorial structure-generation approach for the local
      level modeling of atomic substitutions and partial occupancies in crystals.
AB  - BACKGROUND: Disordered compounds are crucially important for fundamental science
      and industrial applications. Yet most available methods to explore solid-state
      material properties require ideal periodicity, which, strictly speaking, does not
      exist in this type of materials. The supercell approximation is a way to imply
      periodicity to disordered systems while preserving "disordered" properties at the
      local level. Although this approach is very common, most of the reported research
      still uses supercells that are constructed "by hand" and ad-hoc. RESULTS: This
      paper describes a software named supercell, which has been designed to facilitate
      the construction of structural models for the description of vacancy or
      substitution defects in otherwise periodically-ordered (crystalline) materials.
      The presented software allows to apply the supercell approximation systematically
      with an all-in-one implementation of algorithms for structure manipulation,
      supercell generation, permutations of atoms and vacancies, charge balancing,
      detecting symmetry-equivalent structures, Coulomb energy calculations and
      sampling output configurations. The mathematical and physical backgrounds of the
      program are presented, along with an explanation of the main algorithms and
      relevant technical details of their implementation. Practical applications of the
      program to different types of solid-state materials are given to illustrate some
      of its potential fields of application. Comparisons of the various algorithms
      implemented within supercell with similar solutions are presented where possible.
      CONCLUSIONS: The all-in-one approach to process point disordered structures,
      powerful command line interface, excellent performance, flexibility and GNU GPL
      license make the supercell program a versatile set of tools for disordered
      structures manipulations.

PMID- 27042217
TI  - Pretreatment neutrophil-lymphocyte ratio is not a significant prognostic factor
      in epidermal growth factor receptor-mutant non-small cell lung cancer patients
      treated with tyrosine kinase inhibitors.
AB  - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a marker of poor prognosis
      in lung cancer patients. However, previous data have been based on an
      heterogeneous population of lung cancer patients and various treatments. In this
      study, we evaluate the prognostic value of NLR in an homogeneous population of
      epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)
      patients. METHODS: We restrospectively evaluated the data of 250 NSCLC patients
      with EGFR mutations. All data are based on first-line treatment. RESULTS: All
      tumors harbored in-frame deletions in exon 19 or an L858R point mutation. Eighty
      five patients were treated with tyrosine kinase inhibitors (TKIs), while 165
      received cytotoxic chemotherapy as first-line treatment. Multivariate survival
      analysis revealed that the NLR was a significant prognostic factor for first-line
      progression-free survival (PFS) in the chemotherapy group (hazard ratio [HR]
      1.882, 95% confidence interval [CI] 1.319-2.686, P = 0.001), but was not
      significant in the TKI group (HR 1.239, 95% CI 0.693-2.215, P = 0.469). The
      response rate (RR) to first-line treatment was 76.5% in the TKI group and 29.5%
      in the chemotherapy group; however, the RR, according to the NLR (<=3 vs. > 3),
      was the same for both groups. CONCLUSIONS: The NLR was a significant prognostic
      factor in the chemotherapy group, but it did not affect either RR or PFS in EGFR
      mutant NSCLC patients treated with TKIs.

PMID- 27042216
TI  - Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic
      conditions.
AB  - Atherosclerosis is a complex inflammatory disease involving aberrant immune and
      tissue healing responses, which begins with endothelial dysfunction and ends with
      plaque development, instability and rupture. The increased risk for coronary
      artery disease in patients with rheumatologic diseases highlights how aberrancy
      in the innate and adaptive immune system may be central to development of both
      disease states and that atherosclerosis may be on a spectrum of immune-mediated
      conditions. Recognition of the tight association between chronic inflammatory
      disease and complications of atherosclerosis will impact the understanding of
      underlying pathogenic mechanisms and change diagnostic and therapeutic approaches
      in patients with rheumatologic syndromes as well as patients with coronary artery
      disease. In this review, we provide a summary of the role of the immune system in
      atherosclerosis, discuss the proposed mechanisms of accelerated atherosclerosis
      seen in association with rheumatologic diseases, evaluate the effect of
      immunosuppression on atherosclerosis and provide updates on available risk
      assessment tools, biomarkers and imaging modalities.

PMID- 27042218
TI  - Chemotherapy with gemcitabine plus cisplatin in patients with advanced thymic
      squamous cell carcinoma: Evaluation of efficacy and toxicity.
AB  - BACKGROUND: Squamous cell carcinoma of the thymus is a rare thymic epithelial
      neoplasm that tends to widely metastasize at initial presentation. Because of its
      rarity, the optimal chemotherapeutic regimen remains uncertain. A gemcitabine and
      cisplatin regimen has shown promising efficacy in the treatment of other squamous
      cell carcinomas. We assessed the efficacy and toxicity of this regimen in
      patients with advanced thymic squamous cell carcinoma. METHODS: Between January
      2003 and December 2012, 13 patients with untreated or unresectable recurrent
      thymic squamous cell carcinomas, who were treated with gemcitabine and cisplatin,
      were retrospectively analyzed. The endpoints in this study were clinical response
      rate, disease control rate, progression-free survival, and overall survival.
      Significant hematological and non-hematological toxicities were also assessed.
      RESULTS: Three patients were in Masaoka stage IVa and 10 were in stage IVb. The
      median number of treatment cycles for the present chemotherapy regimen was four.
      The clinical response and disease control rates were 61.5% and 92.3%,
      respectively. The median progression-free and median overall survival rates were
      14.5 months (95% confidence interval, 9.2-19.8 months) and 50.7 months (95%
      confidence interval, 24.9-76.5 months), respectively. Grade 3/4 hematological
      toxicities were observed in seven (53.8%) patients, and non-hematological
      toxicities were mild. CONCLUSION: This retrospective analysis demonstrated that
      gemcitabine plus cisplatin was active against advanced thymic squamous cell
      carcinoma with manageable toxicity. Gemcitabine may be a novel and alternative
      agent for advanced thymic squamous cell carcinoma.

PMID- 27042219
TI  - Survival after neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for
      resectable esophageal carcinoma: A meta-analysis.
AB  - BACKGROUND: The efficacy of surgery alone for patients with locally advanced
      esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy
      followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and
      chemoradiation (CRT) are proven effective induction therapies; however, few
      sample studies have addressed these treatments, thus, their superiority remains
      uncertain. We performed a systemic review and meta analysis to test the
      hypothesis that induction CRT prior to surgery could improve survival compared
      with induction CT alone. METHODS: A comprehensive search of PubMed and the Ovid
      database for relevant studies comparing EC patients undergoing resection after
      treatment with induction CT alone or induction CRT was conducted. Hazard ratios
      (HR) and 95% confidence intervals (95% CI) were extracted from these studies to
      provide pooled estimates of the effect of induction therapy on overall survival.
      RESULTS: Five studies met the criteria for analysis. Statistical analysis
      demonstrated a survival benefit of induction CRT compared with induction CT alone
      (HR0.73, 95% CI 0.61-0.89; P = 0.002). Further analysis showed that induction CRT
      perioperative mortality and complication rates were higher than for induction CT
      alone (HR 2.96, 95% CI 1.38-6.37; HR1.6, 95% CI 1.30-1.98; P = 0.01,
      respectively). CONCLUSIONS: Published evidence comparing the different efficacies
      of induction CT and induction CRT is sparse, with few samples of adenocarcinoma.
      This analysis supports the view that, compared with induction CT, induction CRT
      could achieve a long-term survival benefit in EC patients.

PMID- 27042220
TI  - Radical thoracic radiotherapy may provide favorable outcomes for stage IV non
      small cell lung cancer.
AB  - BACKGROUND: This study investigates the outcome of synchronous stage IV non-small
      cell lung cancer (NSCLC) patients who received radical thoracic radiotherapy
      (TRT). METHODS: We retrospectively reviewed the charts of stage IV NSCLC patients
      treated with TRT between January 2007 and December 2011. Radiotherapy was
      considered radical if it was the primary therapy with non-symptom driven intent,
      or consolidation therapy after initial chemotherapy and the biologically
      equivalent dose >=53 Gy halted disease progression. The patients' demographics,
      disease characteristics, and treatment parameters were uniformly collected.
      RESULTS: Eighty-one patients were irradiated with radical intent, including 52%
      with more than five metastatic lesions. The minimum follow-up was 31.5 months for
      survivors. The median overall survival (OS) was 20.8 months, with three and four
      year OS rates of 23% and 18%, respectively. The median progression-free survival
      (PFS) was 8.2 months, with one and two-year PFS rates of 23% and 9%,
      respectively. Partial response (PR) after TRT and administration of targeted
      therapy were predictive of longer OS. The factors associated with favorable PFS
      included earlier local tunor node stage, absence of concurrent chemotherapy, and
      post-TRT PR. No correlation was found between the number of metastatic lesions
      and survival outcome. Incidences of grade >=2 toxicities in the lung and
      esophagus were 9% and 26%, respectively. CONCLUSIONS: Radical TRT may result in
      advantageous outcomes for selected stage IV NSCLC patients, regardless of the
      number of metastatic foci. Patients who achieved post-TRT PR attained the best
      outcomes.

PMID- 27042221
TI  - Anti-apoptotic brain and reproductive organ-expressed proteins enhance cisplatin
      resistance in lung cancer cells via the protein kinase B signaling pathway.
AB  - BACKGROUND: Cisplatin-based chemotherapy is the standard first-line treatment for
      non-small-cell lung cancers (NSCLCs); however, the long-term therapeutic effect
      is reduced by chemoresistance. Brain and reproductive organ-expressed (BRE)
      proteins are overexpressed in several cancers and have an anti-apoptotic
      function. However, their biological role in the development of the chemoresistant
      phenotype of human NSCLC remains unknown. We investigate the differential
      expression of the BRE gene in human lung adenocarcinoma cell lines A549 and the
      cisplatin-resistant variant A549/cisplatin (DDP), and the mechanisms of cisplatin
      resistance induced by the BRE gene. METHODS: Cell counting kit-8 assay was
      employed to determine the sensitivity of A549 and A549/DDP cell lines to
      cisplatin. BRE expression was measured using quantitative real time-polymerase
      chain reaction and western blot analysis. The apoptosis rate of lung
      adenocarcinoma cells was determined by flow cytometry. RESULTS: BRE expression in
      A549 cells, derived from human lung cells, was markedly decreased compared with
      parental cisplatin-resistant A549/DDP cells at messenger ribonucleic acid and
      protein levels. BRE overexpression in A549 significantly decreased sensitivity to
      DDP by inhibiting cell apoptosis. Conversely, BRE knockdown in A549/DDP cells
      increased their chemosensitivity. Importantly, we demonstrate that BRE
      overexpression induces the expression of phosphoprotein kinase B (p-Akt) in lung
      cancer cells, while BRE silencing inhibits p-Akt expression. Furthermore,
      downregulation of p-Akt by LY294002 reversed the DDP resistance induced by BRE by
      increasing apoptosis. BRE enhances the DDP resistance of lung cancer cells
      through the Akt signaling pathway. CONCLUSION: Our findings provide new insight
      into the mechanism of DDP resistance in NSCLC cells and suggest BRE as an
      attractive new target for NSCLC treatment.

PMID- 27042222
TI  - Feasibility and strategy for left tracheobronchial lymph node dissection in
      thoracolaparoscopic esophageal cancer surgery.
AB  - BACKGROUND: This study evaluates the feasibility and strategy of left
      tracheobronchial lymph node (LN) dissection in the surgical treatment of
      esophageal cancer, and its impact on surgical outcomes following thoracoscopic
      esophagectomy. METHODS: Data of 265 patients with thoracic esophageal cancer who
      underwent thoracoscopic and laparoscopic esophagectomy was retrospectively
      reviewed. In 80 cases, thoracoscopic esophagectomy was performed without left
      tracheobronchial LN dissection (group non-4L), while 185 cases underwent
      thoracoscopic esophageal mobilization with routine left tracheobronchial node
      dissection (group 4L). We introduced a "mesoesophageal suspension" method in
      order to facilitate complete dissection of the left tracheobronchial nodes, along
      with left recurrent laryngeal nerve nodes. Both univariate and multivariate
      analyses were performed to evaluate risk factors correlated to left
      tracheobronchial node metastasis. RESULTS: The non-4L group experienced less
      blood loss than the 4L group (P = 0.009). More mediastinal LNs were dissected in
      the 4L group (P < 0.001). There was no significant difference with regard to the
      incidence of major postoperative complications between the two groups. Compared
      with other LN metastases, the metastatic rate of the left tracheobronchial LNs
      was relatively lower. Based on multivariate analysis of six factors, lymphatic
      invasion and subcarinal node metastasis were shown to be strong independent
      predictors of left tracheobronchial metastasis. CONCLUSION: Routine thoracoscopic
      extensive lymphadenectomy, including the left tracheobronchial LN, was
      technically feasible and safe in patients with esophageal cancer. Using a
      mesoesophagus suspension technique, we performed a meticulous LN dissection in
      the upper mediastinal space.

PMID- 27042223
TI  - Safety and efficacy of single-agent docetaxel (Taxotere) administered weekly in
      non-small cell lung carcinoma patients in Korea: An observational study.
AB  - BACKGROUND: To investigate the efficacy, safety, and tolerability of weekly
      docetaxel treatment in advanced non-small cell lung cancer (NSCLC) patients in
      Korea. METHODS: This prospective observational study included Korean advanced
      NSCLC patients with Eastern Cooperative Oncology Group performance status <2 who
      received weekly monotherapy of docetaxel at a dose determined by the physician.
      Efficacy measurements included tumor response rate, overall survival (OS),
      progression-free survival, and one-year survival rate. Safety was analyzed
      through recorded incidences of adverse events (AEs), serious adverse events
      (SAEs), deaths, and other related safety parameters, along with their toxicity
      grades. RESULTS: Of 274 patients analyzed, one patient achieved a complete
      response and 42 partial responses; thus, the overall response rate was 15.7%. The
      OS rate at baseline and at one-year follow-up was 38.3% and 33.8%, respectively.
      AEs were reported in 229 (83.6%) patients. The most frequently reported
      hematologic AE of grade >=3 was a decrease in neutrophils, with 6.6% of the
      patients developing neutropenia. In non-hematologic AEs of grade >=3, the most
      common were infection with unknown absolute neutrophil count and death not
      associated with Common Terminology Criteria for Adverse Events (CTCAE) (4.7%
      each). The most common SAE reported was death, not associated with CTCAE (7.3%).
      CONCLUSIONS: In Korean patients, the weekly regimen of docetaxel monotherapy was
      safe and efficacious against advanced NSCLC.

PMID- 27042224
TI  - Clinical analysis of sixty-four patients with T1aN2M0 stage non-small cell lung
      cancer who had undergone resection.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical features of
      T1aN2M0 stage non-small cell lung cancer (NSCLC). METHOD: From November 2008 to
      May 2013, 498 patients with T1a-stage NSCLC who visited the Shanghai Cancer
      Center were included in the study. All patients underwent a lobectomy or
      segmentectomy with systematic nodal resection for primary lung cancer. Analyses
      of gender, smoking history, primary tumor site, tumor location, tumor size,
      pathological classification, cancer gene, pleural invasion, number of positive
      lymph nodes, skip N2, single or multiple station N2, progression-free survival
      (PFS), and overall survival (OS) were performed. RESULT: There were significant
      differences in tumor size, tumor size distribution, adenocarcinoma subgroup, and
      number of positive lymph nodes between patients at T1aN2M0 and T1aN0M0 stages.
      The most common histology of the T1aN2M0 subgroup was adenocarcinoma. Epidermal
      growth factor receptor mutations were the most common gene mutation in T1aN2M0
      stage NSCLC. There were significant differences in five-year OS and PFS rates
      between patients with T1aN2M0, T1aN0M0, and T1aN1M0 stages. Multivariate analyses
      of mediastinal lymph node metastasis showed that gender, tumor size distribution,
      and histology type were significant predictive factors. Multivariate analyses of
      OS and PFS rates in the T1aN2M0 subgroup showed that the number of positive lymph
      nodes was a significant predictive factor. CONCLUSION: Gender, tumor size
      distribution, and histology type were independent predictors of mediastinal lymph
      node metastasis in patients with T1a stage. The number of positive lymph nodes
      was significantly associated with OS and PFS rates in patients with T1aN2M0 stage
      NSCLC.

PMID- 27042225
TI  - Efficacy and safety of the combination of paclitaxel and platinum in advanced
      thymic carcinoma.
AB  - This study aimed to assess the efficacy and safety of a combination of paclitaxel
      and cisplatin/carboplatin for the treatment of advanced thymic carcinoma. Thirty
      seven patients (23 men and 14 women, median age 47 years, performance status
      score <=2) with pathologically or cytologically diagnosed advanced thymic
      carcinoma were recruited. Patients received 175 mg/m(2) paclitaxel on day 1 and
      75 mg/m(2) cisplatin or 300 mg/m(2) carboplatin on day 2 of a 21 day cycle for at
      least two cycles to evaluate efficacy and adverse events. No complete response
      (CR) was observed; 11 patients had a partial response (PR), 16 patients had no
      change (NC), and 10 had progressive disease, resulting in an overall response
      rate of 29.7%, a stable rate of 43.2%, and a disease control rate (CR + PR + NC)
      of 72.9%. Grade I/II and III/IV neutropenia were observed in 21 (56.7%) and 13
      (35.1%) patients, respectively. Four (10.8%) patients developed grade I/II
      thrombocytopenia. Grade I/II and III/IV nausea and vomiting were observed in 19
      (51.2%) and five (13.5%) patients, respectively. Grade I/II liver dysfunction was
      observed in seven (18.9%) patients. Two patients with grade III liver dysfunction
      recovered after hepatoprotective treatment. The combination of paclitaxel and
      platinum was effective and well tolerated in patients with advanced thymic
      carcinoma. 

PMID- 27042226
TI  - Upregulation of microrna-451 increases the sensitivity of A549 cells to
      radiotherapy through enhancement of apoptosis.
AB  - BACKGROUND: As radioresistance of non-small cell lung cancers (NSCLC) is one of
      the main causes of failure in radiotherapy, we examined whether micro ribonucleic
      acid (miR-451) could function as a potential radiosensitizer of NSCLC and the
      related mechanism. METHODS: Radioresistant NSCLC cell line A549 was transfected
      with pre-miR-451 or a scrambled control. The miR-451 messenger RNA level, colony
      forming ability, apoptosis, and phosphatase and tensin homolog (PTEN) protein
      level of 549 cells were examined by real-time polymerase chain reaction,
      clonogenic assay, flow cytometry analysis, and Western blot. RESULTS:
      Upregulation of miR-451 enhanced the suppressive effects of irradiation on the
      colony-forming ability of A549 cells. The apoptosis and PTEN expression of A549
      cells post-irradiation were also enhanced by upregulation of miR-451.
      CONCLUSIONS: Upregulation of miR-451 sensitized radioresistant NSCLC A549 cells
      to irradiation through the enhancement of apoptosis. The activation of PTEN post
      irradiation was possibly correlated with the radiosensitization of A549 cells
      induced by miR-451 overexpression.

PMID- 27042227
TI  - Esophageal cancer statistics in China, 2011: Estimates based on 177 cancer
      registries.
AB  - BACKGROUND: Esophageal cancer has been a common cancer in China for many years.
      Using the most recent data collected from the National Central Cancer Registry,
      we present estimates of the esophageal cancer burden in China in 2011. METHODS:
      Age-specific incidence and mortality rates by gender and area for 18 age groups
      were calculated based on data from 177 qualified population-based cancer
      registries. The number of new cases of esophageal cancer and cancer deaths were
      computed by multiplying these rates by the 2011 population. Crude incidence and
      mortality rates of esophageal cancer were estimated. RESULTS: The estimated
      number of new esophageal cancer cases and deaths were 291 238 and 218 957,
      respectively. The crude incidence and mortality rates for esophageal cancer were
      21.62/100 000 and 16.25/100 000, respectively. The age-standardized incidence and
      mortality rates by world population were 15.83/100 000 and 11.62/100 000,
      respectively. Both the incidence and mortality rates of esophageal cancer were
      higher in rural areas than in urban areas, and in men than in women. The age
      specific esophageal cancer incidence and mortality rates increased with age. In
      China, squamous cell cancer was the most common pathological type of the disease.
      CONCLUSION: Esophageal cancer remains a major public health issue in China.
      Primary and secondary prevention are essential for disease control.

PMID- 27042228
TI  - Incidence rate of lung cancer in urban Shijiazhuang in 2012 with prevention
      implication.
AB  - BACKGROUND: Pollution has been established as an environmental factor in the
      development of lung cancer; however, the incidence rate in Shijiazhuang, one of
      China's most heavily polluted cities, is unknown. METHODS: As Chinese citizens
      are entitled to complete public medical insurance coverage, we estimated the lung
      cancer incidence rate among registered citizens of urban Shijiazhuang in 2012
      using reimbursement records of first hospitalization. RESULTS: In Shijiazhuang,
      lung cancer was the most common cancer in men and the second most common cancer
      in women. The age standardized world incidence rate (ASRW) was 46.42 and
      19.14/100 000, respectively, compared with 51.05 and 22.24/100 000, respectively,
      reported for 63 Chinese tumor registration cities in 2010 (the national level).
      However, age-specific rates for the 55-70 range in men and the 25-55 range in
      women were higher in Shijiazhuang than nationally. Compared with GLOBOCAN 2012
      data, the lung cancer ASRW in Shijiazhuang was comparable to that of all
      industrialized countries (44.7 and 19.6/100 000), but higher than all developing
      countries (30.0 and 11.1/100 000), Japan (38.8 and 12.9/100 000), and Korea (45.5
      and 16.2/100 000). CONCLUSION: The lung cancer incidence rate in Shijiazhuang
      matched the world's highest level in 2012. According to the experience of western
      countries, the incidence rate in China is expected to continue to rise over the
      next 40 years. Intervention is urgently required in order to reduce smoking
      prevalence by a third by 2025 and to take concrete legal action to reduce air
      pollution.

PMID- 27042229
TI  - Irinotecan plus fluorouracil-based regimen as second or third-line chemotherapy
      for recurrent or metastatic esophageal squamous cell carcinoma.
AB  - BACKGROUND: No standard second-line regimen exists for the treatment of advanced
      esophageal squamous cell carcinoma (ESCC). The aim of this study was to evaluate
      the efficacy and safety of irinotecan and fluorouracil-based chemotherapy as a
      second or third-line regimen for advanced ESCC patients. METHODS: We
      retrospectively reviewed a cohort of 27 consecutive patients with advanced ESCC
      in one institute, treated with a combination of irinotecan plus fluorouracil
      based regimens after the failure of first-line platinum-based therapy. Nine
      patients were treated with 150-160 mg/m(2) irinotecan and 400 mg/m(2)
      fluorouracil (5-FU) on day 1, followed by 2000 mg/m(2) 5-FU during a 48-hour
      infusion every two weeks. Eighteen patients received 150-160 mg/m(2) irinotecan
      on day 1 and 80-120 mg/day S-1 on days 1-10 every two weeks. The S-1 dose was
      based on the patients' body surface area. RESULTS: Twenty-four of the 27 patients
      were assessable for response. One (3.7%) patient achieved complete response,
      seven (25.9%) achieved partial response, eight (29.6%) had stable disease, and
      eight (29.6%) had progressive disease. The median progression-free and overall
      survival were 4.8 (95% confidence interval [CI]: 1.2-8.4) and 10.5 months (95%
      CI: 8.4-12.7), respectively. Grade 3 neutropenia and diarrhea were detected in
      four (15%) and one (4%) patient, respectively. No grade 4 toxicity was noted.
      CONCLUSIONS: Our study indicates that an irinotecan plus 5-FU-based regimen is
      effective and well-tolerated as a second or third-line chemotherapy for patients
      with advanced ESCC.

PMID- 27042230
TI  - Pharmacokinetic analysis of gefitinib in a patient with advanced non-small cell
      lung cancer undergoing hemodialysis.
AB  - Patients undergoing hemodialysis (HD) are frequently elderly with poor
      performance status and usually cannot withstand chemotherapy because of its
      toxicities. We report a case of an elderly woman with chronic renal failure
      undergoing HD who was diagnosed with advanced non-small cell lung cancer and
      treated with orally administered gefitinib. We analyzed the pharmacokinetic data
      of gefitinib in this patient and found that that gefitinib was safe under these
      conditions. 

PMID- 27042231
TI  - Lung cancer mimicking aortic dissecting aneurysm in a patient with situs inversus
      totalis.
AB  - Lung cancer and situs inversus totalis are two completely irrelevant conditions.
      The likelihood of both conditions occurring simultaneously in one person is very
      rare. We report here a case of a 50-year-old man who presented with intermittent
      chest pain. Enhanced computed tomography of the chest showed situs inversus
      totalis and a round mediastinal mass embracing the thoracic aorta. The primary
      diagnosis was suggested as pseudo aortic dissecting aneurysm. However, a tumor in
      the right lower lung was discovered during surgery, which enclosed and invaded
      the thoracic aorta. Finally, the patient successfully underwent right lower
      lobectomy accompanied by lymph node excision and partial replacement of the
      thoracic aorta with an artificial vascular graft under cardio-pulmonary bypass.

PMID- 27042232
TI  - Recurrent bilateral spontaneous pneumothorax secondary to lung adenocarcinoma
      with epidermal growth factor receptor mutation.
AB  - A 42-year-old female patient was admitted for recurrent bilateral spontaneous
      pneumothorax. High resolution computed tomography showed bilateral pneumothorax
      and numerous round and oval, thin-walled lung cysts. Microscopically, each small
      cyst was composed of distended subpleural alveolar spaces. Tumor cells,
      characteristic of acinar adenocarcinoma, obstructed and narrowed the terminal
      bronchioles. There was no tumor necrosis or mucin production. This suggested
      check-valve as a possible mechanism of the thin-walled cysts and pneumothorax.
      Genetic analysis suggested that the tumors were positive for epidermal growth
      factor receptor mutation L858R in exon 21. Bilateral spontaneous pneumothorax and
      thin-walled cysts in association with lung cancer is rarely reported and may be
      confused with cystic benign lung lesions.

PMID- 27042233
TI  - Solitary pulmonary metastasis from occult papillary thyroid carcinoma.
AB  - Pulmonary metastases from thyroid carcinoma typically cause a micronodular or
      miliary pattern throughout both lungs. Metastasis consisting of a solitary
      pulmonary nodule measuring 20 mm in diameter is rare. Here we report a case of a
      66-year-old woman without a history of papillary thyroid carcinoma who presented
      with a pulmonary nodule measuring 20 mm in diameter, found on chest computed
      tomography during a health checkup. The patient underwent a right lobectomy.
      Microscopic examination showed well-differentiated papillary adenocarcinoma.
      Immunohistochemical findings were consistent with a diagnosis of pulmonary
      metastasis from papillary thyroid carcinoma. Solitary metastasis to the lung from
      occult thyroid carcinoma is quite rare, but if a pulmonary nodule is encountered
      in a patient without a history of thyroid carcinoma, the possibility must be
      considered. 

PMID- 27042234
TI  - Comparison of 19-gauge eXcelon and WANG MW-319 transbronchial aspiration needles.
AB  - Conventional transbronchial needle aspiration (TBNA) using 19-gauge needles can
      obtain larger histological specimens for hilar-mediastinal diagnosis. A new 19
      gauge eXcelon needle was introduced in Taiwan in July 2012. We prospectively
      enrolled patients with hilar-mediastinal lesions and pathology results of
      suspected benign origin or lymphoproliferative processes, to perform TBNA using a
      19-gauge eXcelon needle, between July 2012 and December 2012. The results were
      compared with historical control of TBNA using a WANG MW-319 needle between
      January 2011 and June 2012. The procedure was performed by the same
      pulmonologist, and rapid on-site cytologic evaluation was used. The 19-gauge
      eXcelon needle was used in nine patients with 15 lymph nodes aspirated, with a
      mean diameter of 23.3 +/- 10.7 mm. The mean number of needle passes was 2.7 +/-
      1.4, with a diagnostic accuracy of 77.8%. The MW-319 needle was used in 12
      patients with 18 lymph nodes aspirated, with a mean diameter of 21.3 +/- 5.7 mm.
      The mean number of needle passes was 2.2 +/- 0.4, with a diagnostic accuracy of
      75.0%. Neither technical nor major clinical complications were noted in either
      group. We concluded that the 19-gauge eXcelon needle was as safe and effective as
      the MW-319 needle. A more adequate specimen could be obtained and fewer needle
      passes were required with the MW-319 needle, although the difference did not
      reach significance.

PMID- 27042235
TI  - Active recombinant Tol2 transposase for gene transfer and gene discovery
      applications.
AB  - BACKGROUND: The revolutionary concept of "jumping genes" was conceived by
      McClintock in the late 1940s while studying the Activator/Dissociation (Ac/Ds)
      system in maize. Transposable elements (TEs) represent the most abundant
      component of many eukaryotic genomes. Mobile elements are a driving force of
      eukaryotic genome evolution. McClintock's Ac, the autonomous element of the Ac/Ds
      system, together with hobo from Drosophila and Tam3 from snapdragon define an
      ancient and diverse DNA transposon superfamily named hAT. Other members of the
      hAT superfamily include the insect element Hermes and Tol2 from medaka. In recent
      years, genetic tools derived from the 'cut' and 'paste' Tol2 DNA transposon have
      been widely used for genomic manipulation in zebrafish, mammals and in cells in
      vitro. RESULTS: We report the purification of a functional recombinant Tol2
      protein from E.coli. We demonstrate here that following microinjection using a
      zebrafish embryo test system, purified Tol2 transposase protein readily catalyzes
      gene transfer in both somatic and germline tissues in vivo. We show that purified
      Tol2 transposase can promote both in vitro cutting and pasting in a defined
      system lacking other cellular factors. Notably, our analysis of Tol2
      transposition in vitro reveals that the target site preference observed for Tol2
      in complex host genomes is maintained using a simpler target plasmid test system,
      indicating that the primary sequence might encode intrinsic cues for transposon
      integration. CONCLUSIONS: This active Tol2 protein is an important new tool for
      diverse applications including gene discovery and molecular medicine, as well as
      for the biochemical analysis of transposition and regulation of hAT
      transposon/genome interactions. The measurable but comparatively modest insertion
      site selection bias noted for Tol2 is largely determined by the primary sequence
      encoded in the target sequence as assessed through studying Tol2 protein-mediated
      transposition in a cell-free system.

PMID- 27042236
TI  - Poly(ethylene glycol) Hydrogel Scaffolds Containing Cell-Adhesive and Protease
      Sensitive Peptides Support Microvessel Formation by Endothelial Progenitor Cells.
AB  - The development of stable, functional microvessels remains an important obstacle
      to overcome for tissue engineered organs and treatment of ischemia. Endothelial
      progenitor cells (EPCs) are a promising cell source for vascular tissue
      engineering as they are readily obtainable and carry the potential to
      differentiate towards all endothelial phenotypes. The aim of this study was to
      investigate the ability of human umbilical cord blood-derived EPCs to form vessel
      like structures within a tissue engineering scaffold material, a cell-adhesive
      and proteolytically degradable poly(ethylene glycol) (PEG) hydrogel. EPCs in co
      culture with angiogenic mural cells were encapsulated in hydrogel scaffolds by
      mixing with polymeric precursors and using a mild photocrosslinking process to
      form hydrogels with homogeneously dispersed cells. EPCs formed 3D microvessels
      networks that were stable for at least 30 days in culture, without the need for
      supplemental angiogenic growth factors. These 3D EPC microvessels displayed
      aspects of physiological microvasculature with lumen formation, expression of
      endothelial cell proteins (connexin 32, VE-cadherin, eNOS), basement membrane
      formation with collagen IV and laminin, perivascular investment of PDGFR-beta and
      alpha-SMA positive cells, and EPC quiescence (<1% proliferating cells) by 2 weeks
      of co-culture. Our findings demonstrate the development of a novel, reductionist
      system that is well-defined and reproducible for studying progenitor cell-driven
      microvessel formation.

PMID- 27042237
TI  - Effect of Pseudopod Extensions on Neutrophil Hemodynamic Transport Near a Wall.
AB  - During inflammation, circulating neutrophils roll on, and eventually tether to,
      the endothelial lining of blood vessels, allowing them to exit the bloodstream
      and enter the surrounding tissue to target pathogens. This process is mediated by
      the selectin family of adhesion proteins expressed by endothelial cells.
      Interestingly, only 10% of activated, migrating neutrophils transmigrate into the
      extravascular space; the other 90% detach from the wall and rejoin the blood
      flow. Neutrophils extrude pseudopods during the adhesion cascade; however, the
      transport behavior of this unique cell geometry has not been previously
      addressed. In this study, a three-dimensional computational model was applied to
      neutrophils with pseudopodial extensions to study the effect of cell shape on the
      hydrodynamic transport of neutrophils. The collision time, contact area, contact
      force, and collision frequency were analyzed as a function of pseudopod length.
      It was found that neutrophils experience more frequent collisions compared to
      prolate spheroids of equal volume and length. Longer pseudopods and lower shear
      rates increase the collision time integral contact area, a predictor of binding
      potential. Our results indicate that contact between the neutrophil and the
      vessel wall was found to be focused predominantly on the pseudopod tip.

PMID- 27042239
TI  - The Role of Teachers in School-Based Suicide Prevention: A Qualitative Study of
      School Staff Perspectives.
AB  - In response to concerns over youth suicide, there has been an increase in school
      based suicide prevention programs. However, we know little about teacher
      perspectives on school-based suicide prevention and mental health programs. This
      study examined teacher roles in the implementation of a district-wide suicide
      prevention program through focus groups and interviews with middle school
      teachers, administrators, and other school personnel. Study results highlighted
      teachers' critical role in detecting students at risk for suicide. Factors that
      appeared to facilitate teacher participation in the suicide prevention program
      included well-defined crisis policies and procedures, communication of these
      procedures, collaboration across staff, and the presence of on-campus mental
      health resources. Participants identified a need for direct teacher training on
      risk factors for suicide, crisis response, and classroom management. Other
      strategies for improving suicide prevention efforts included in-school trainings
      on mental health resources and procedures, regular updates to these trainings,
      and greater visibility of mental health staff.

PMID- 27042238
TI  - Specific pattern of maturation and differentiation in the formation of cortical
      tubers in tuberous sclerosis omplex (TSC): evidence from layer-specific marker
      expression.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disorder that
      results from mutations in the TSC1 or TSC2 genes, leading to constitutive
      activation of the mammalian target of rapamycin (mTOR) signaling pathway.
      Cortical tubers represent typical lesions of the central nervous system (CNS) in
      TSC. The pattern of cortical layering disruption observed in brain tissue of TSC
      patients is not yet fully understood, and little is known about the origin and
      phenotype of individual abnormal cell types recognized in tubers. METHODS: In the
      present study, we aimed to characterize dysmorphic neurons (DNs) and giant cells
      (GCs) of cortical tubers using neocortical layer-specific markers (NeuN, SMI32,
      Tbr1, Satb2, Cux2, ER81, and RORbeta) and to compare the features with the histo
      morphologically similar focal cortical dysplasia (FCD) type IIb. We studied a
      cohort of nine surgically resected cortical tubers, five FCD type IIb, and four
      control samples using immunohistochemistry and in situ hybridization. RESULTS:
      Cortical tuber displayed a prominent cell loss in all cortical layers. Moreover,
      we observed altered proportions of layer-specific markers within the dysplastic
      region. DNs, in both tubers and FCD type IIb, were found positive for different
      cortical layer markers, regardless of their laminar location, and their
      immunophenotype resembles that of cortical projection neurons. CONCLUSIONS: These
      findings demonstrate that, similar to FCD type IIb, cortical layering is markedly
      disturbed in cortical tubers of TSC patients. Distribution of these disturbances
      is comparable in all tubers and suggests a dysmaturation affecting early and late
      migratory patterns, with a more severe impairment of the late stage of
      maturation.

PMID- 27042240
TI  - Ambient and smartphone sensor assisted ADL recognition in multi-inhabitant smart
      environments.
AB  - Activity recognition in smart environments is an evolving research problem due to
      the advancement and proliferation of sensing, monitoring and actuation
      technologies to make it possible for large scale and real deployment. While
      activities in smart home are interleaved, complex and volatile; the number of
      inhabitants in the environment is also dynamic. A key challenge in designing
      robust smart home activity recognition approaches is to exploit the users'
      spatiotemporal behavior and location, focus on the availability of multitude of
      devices capable of providing different dimensions of information and fulfill the
      underpinning needs for scaling the system beyond a single user or a home
      environment. In this paper, we propose a hybrid approach for recognizing complex
      activities of daily living (ADL), that lie in between the two extremes of
      intensive use of body-worn sensors and the use of ambient sensors. Our approach
      harnesses the power of simple ambient sensors (e.g., motion sensors) to provide
      additional 'hidden' context (e.g., room-level location) of an individual, and
      then combines this context with smartphone-based sensing of micro-level
      postural/locomotive states. The major novelty is our focus on multi-inhabitant
      environments, where we show how the use of spatiotemporal constraints along with
      multitude of data sources can be used to significantly improve the accuracy and
      computational overhead of traditional activity recognition based approaches such
      as coupled-hidden Markov models. Experimental results on two separate smart home
      datasets demonstrate that this approach improves the accuracy of complex ADL
      classification by over 30 %, compared to pure smartphone-based solutions.

PMID- 27042241
TI  - Detection and monitoring of hypermethylated RASSF1A in serum from patients with
      metastatic breast cancer.
AB  - BACKGROUND: Circulating hypermethylated RASSF1A could be a novel and potential
      useful marker for monitoring patients with metastatic breast cancer. Technical
      obstacles include fragmentation of the circulating DNA, fluctuations in the
      concentration, low concentrations of circulating tumor DNA, and different
      locations of methylation in the RASSF1A gene among patients. One common method
      for detection of hypermethylated genes is sodium bisulfite conversion of non
      methylated cytosine to uracil, followed by detection with PCR. However, the
      method relies on full conversion of all non-methylated cytosines, cause strand
      breaks, and loss of DNA. Alternatively, methylation-sensitive restriction enzymes
      have been used to digest genomic DNA, as well as sodium bisulfite-treated DNA. By
      flanking different regions of the RASSF1A with different PCR primer pairs, we
      analyzed for methylated genomic regions resistant to cleavage by the methylation
      sensitive restriction enzymes HpaII and BstUI. The goal was to find region(s) in
      RASSF1A with high sensitivity and specificity that could be used for monitoring.
      RESULTS: The serum was spiked with non-human control DNA. By tracing the spiking
      control, the isolation procedure of the rare circulating tumor DNA was initially
      optimized. By analysis of production of PCR amplicons from HpaII- or BstUI
      treated DNA isolated from 24 patients with metastatic breast cancer, we located
      four regions resulting in sensitivities from 63 to 83 %. When examining samples
      from 24 control subjects, these four regions gave a specificity of 100 %. Among
      these four regions, the primer pair with the highest PCR efficacy was selected to
      monitor the RASSF1A concentration in 31 collected serum samples. The spiked DNA
      was then used to calculate the tumor RASSF1A concentrations independent of
      fluctuations in circulating non-tumor DNA. As a proof of principle, there was
      concordance in the kinetics of the RASSF1A and the serological cancer biomarkers
      CA 15-3, CEA, and TPA. CONCLUSIONS: Methylation-sensitive restriction enzymes may
      be a useful methodological approach for monitoring circulating hypermethylated
      RASSF1A among patients with metastatic breast cancer.

PMID- 27042242
TI  - First results of the double-blind randomized placebo-controlled multicenter
      clinical trial of DIM-based therapy designed as personalized approach to reverse
      prostatic intraepithelial neoplasia (PIN).
AB  - BACKGROUND: Targeted pharmacological correction is used extensively in medical
      practice today. 3,3'-Diindolylmethane (DIM) is known as a substance with various
      anticancer properties. An interim study of the efficacy of a new drug Infemin on
      the basis of diindolylmethane (DIM) with improved bioavalability has been
      conducted. METHODS: The clinical trial had a multicenter, randomized, placebo
      controlled, double-blind design and was carried out in two parallel groups. The
      interim analysis of data included 21 patients diagnosed with a high-grade
      prostatic intraepithelial neoplasia (PIN). Group 1 (11 patients) received Infemin
      in a dose of 900 mg of DIM a day, and group 2 (10 patients) received placebo. To
      assess the efficacy of therapy, the analysis of morphological index (MI) changes
      based on the results of histological examinations of prostate biopsy specimens
      was performed, and a proportion of patients with persistent PIN in 12 months
      after Infemin initiation was calculated. Researchers also evaluated prostate
      size, urodynamic parameters (Qmax, Qave, Vres), IPSS, and QoL (quality of life)
      indices and International Index of Erectile Function (IIEF) at 3, 6, 9, and 12
      months after the Infemin administration start. RESULTS: After 12 months of
      treatment in the Infemin group, MI decreased from 0.50 to 0.08, while in the
      placebo group, it increased from 0.27 to 0.58; the difference between the groups
      was statistically significant (p = 0.0003, Mann-Whitney test). In 45.5 % of
      patients in the Infemin group, a complete regression of PIN was also observed,
      while in the placebo group, PIN regression was not observed in any patients (p =
      0.053, Yates' corrected chi-square). Study results in the Infemin group show
      improvement of maximal urinary flow rate Qmax (53.3 % increase compared to the
      initial value); however, the statistical significance was not reached (p = 0.180,
      Mann-Whitney test) due to the small sample size. Evaluation of other urodynamic
      parameters, prostate volume, quality of life, symptoms reflecting urination
      disorder, and erectile dysfunction symptoms did not reveal significant
      differences between the Infemin and placebo groups either which is probably due
      to the small sample size. CONCLUSIONS: The intermediate results of the 21
      patients in this multicenter, randomized, placebo-controlled, double-blind study
      show that Infemin may be a promising drug candidate in patients with  high-grade
      PIN. TRIAL REGISTRATION: www.chictr.org.cnChiCTR-INR-15007496.

PMID- 27042243
TI  - Flexible Bayesian survival modeling with semiparametric time-dependent and shape
      restricted covariate effects.
AB  - Presently, there are few options with available software to perform a fully
      Bayesian analysis of time-to-event data wherein the hazard is estimated semi- or
      non-parametrically. One option is the piecewise exponential model, which requires
      an often unrealistic assumption that the hazard is piecewise constant over time.
      The primary aim of this paper is to construct a tractable semiparametric
      alternative to the piecewise exponential model that assumes the hazard is
      continuous, and to provide modifiable, user-friendly software that allows the use
      of these methods in a variety of settings. To accomplish this aim, we use a novel
      model formulation for the log-hazard based on a low-rank thin plate linear spline
      that readily facilitates adjustment for covariates with time-dependent and
      proportional hazards effects, possibly subject to shape restrictions. We
      investigate the performance of our model choices via simulation. We then analyze
      colorectal cancer data from a clinical trial comparing the effectiveness of two
      novel treatment regimes relative to the standard of care for overall survival. We
      estimate a time-dependent hazard ratio for each novel regime relative to the
      standard of care while adjusting for the effect of aspartate transaminase, a
      biomarker of liver function, that is subject to a non-decreasing shape
      restriction.

PMID- 27042244
TI  - Pre-Surgical fMRI Data Analysis Using a Spatially Adaptive Conditionally
      Autoregressive Model.
AB  - Spatial smoothing is an essential step in the analysis of functional magnetic
      resonance imaging (fMRI) data. One standard smoothing method is to convolve the
      image data with a three-dimensional Gaussian kernel that applies a fixed amount
      of smoothing to the entire image. In pre-surgical brain image analysis where
      spatial accuracy is paramount, this method, however, is not reasonable as it can
      blur the boundaries between activated and deactivated regions of the brain.
      Moreover, while in a standard fMRI analysis strict false positive control is
      desired, for pre-surgical planning false negatives are of greater concern. To
      this end, we propose a novel spatially adaptive conditionally autoregressive
      model with variances in the full conditional of the means that are proportional
      to error variances, allowing the degree of smoothing to vary across the brain.
      Additionally, we present a new loss function that allows for the asymmetric
      treatment of false positives and false negatives. We compare our proposed model
      with two existing spatially adaptive conditionally autoregressive models.
      Simulation studies show that our model outperforms these other models; as a real
      model application, we apply the proposed model to the pre-surgical fMRI data of
      two patients to assess peri- and intra-tumoral brain activity.

PMID- 27042245
TI  - Generation of micro-sized PDMS particles by a flow focusing technique for
      biomicrofluidics applications.
AB  - Polydimethylsiloxane (PDMS), due to its remarkable properties, is one of the most
      widely used polymers in many industrial and medical applications. In this work, a
      technique based on a flow focusing technique is used to produce PDMS spherical
      particles with sizes of a few microns. PDMS precursor is injected through a
      hypodermic needle to form a film/reservoir over the needle's outer surface. This
      film flows towards the needle tip until a liquid ligament is steadily ejected
      thanks to the action of a coflowing viscous liquid stream. The outcome is a
      capillary jet which breaks up into PDMS precursor droplets due to the growth of
      capillary waves producing a micrometer emulsion. The PDMS liquid droplets in the
      solution are thermally cured into solid microparticles. The size distribution of
      the particles is analyzed before and after curing, showing an acceptable degree
      of monodispersity. The PDMS liquid droplets suffer shrinkage while curing. These
      microparticles can be used in very varied technological fields, such as
      biomedicine, biotechnology, pharmacy, and industrial engineering. 

PMID- 27042246
TI  - Microfluidic cell fragmentation for mechanical phenotyping of cancer cells.
AB  - Circulating tumor cells (CTCs) shed from the primary tumor undergo significant
      fragmentation in the microvasculature, and very few escape to instigate
      metastases. Inspired by this in vivo behavior of CTCs, we report a microfluidic
      method to phenotype cancer cells based on their ability to arrest and fragment at
      a micropillar-based bifurcation. We find that in addition to cancer cell size,
      mechanical properties determine fragmentability. We observe that highly
      metastatic prostate cancer cells are more resistant to fragmentation than weakly
      metastatic cells, providing the first indication that metastatic CTCs can escape
      rupture and potentially initiate secondary tumors. Our method may thus be useful
      in identifying phenotypes that succumb to or escape mechanical trauma in
      microcirculation. 

PMID- 27042247
TI  - Development of three-dimensional integrated microchannel-electrode system to
      understand the particles' movement with electrokinetics.
AB  - An optical transparent 3-D Integrated Microchannel-Electrode System (3-DIMES) has
      been developed to understand the particles' movement with electrokinetics in the
      microchannel. In this system, 40 multilayered electrodes are embedded at the 2
      opposite sides along the 5 square cross-sections of the microchannel by using
      Micro Electro-Mechanical Systems technology in order to achieve the optical
      transparency at the other 2 opposite sides. The concept of the 3-DIMES is that
      the particles are driven by electrokinetic forces which are dielectrophoretic
      force, thermal buoyancy, electrothermal force, and electroosmotic force in a
      three-dimensional scope by selecting the excitation multilayered electrodes. As a
      first step to understand the particles' movement driven by electrokinetic forces
      in high conductive fluid (phosphate buffer saline (PBS)) with the 3-DIMES, the
      velocities of particles' movement with one pair of the electrodes are measured
      three dimensionally by Particle Image Velocimetry technique in PBS; meanwhile,
      low conductive fluid (deionized water) is used as a reference. Then, the
      particles' movement driven by the electrokinetic forces is discussed
      theoretically to estimate dominant forces exerting on the particles. Finally,
      from the theoretical estimation, the particles' movement mainly results from the
      dominant forces which are thermal buoyancy and electrothermal force, while the
      velocity vortex formed at the 2 edges of the electrodes is because of the
      electroosmotic force. The conclusions suggest that the 3-DIMES with PBS as high
      conductive fluid helps to understand the three-dimensional advantageous flow
      structures for cell manipulation in biomedical applications. 

PMID- 27042248
TI  - Ultraviolet-assisted microfluidic generation of ferroelectric composite
      particles.
AB  - We report on the feasible fabrication of microfluidic devices for ferroelectric
      polymers' synthesis in a rapid and stable fashion. Utilizing micro-mixing and
      flow-focusing in microchannels, poly(vinylidene fluoride-trifluoroethylene) and
      copper phthalocyanine are uniformly dispersed in one hydrogel particle, which are
      then demonstrated to immediate and complete on-chip steady polymerization by
      moderate ultraviolet treatment. The advantage of our droplet-based microfluidic
      devices is generating versatile particles from simple spheres to disks or rods,
      and the lengths of particles can be precisely tuned from 30 to 400 MUm through
      adjusting the flow rates of both disperse and oil phases. In addition, this mixed
      technique allows for the continuous production of dielectric microparticles with
      controlled dielectric properties between 10 and 160. Such a microfluidic device
      offers a flexible platform for multiferroic applications. 

PMID- 27042249
TI  - Fabrication of universal serial bus flash disk type microfluidic chip
      electrophoresis and application for protein analysis under ultra low voltage.
AB  - A simple and effective universal serial bus (USB) flash disk type microfluidic
      chip electrophoresis (MCE) was developed by using poly(dimethylsiloxane) based
      soft lithography and dry film based printed circuit board etching techniques in
      this paper. The MCE had a microchannel diameter of 375 MUm and an effective
      length of 25 mm. Equipped with a conventional online electrochemical detector,
      the device enabled effectively separation of bovine serum albumin, lysozyme, and
      cytochrome c in 80 s under the ultra low voltage from a computer USB interface.
      Compared with traditional capillary electrophoresis, the USB flash disk type MCE
      is not only portable and inexpensive but also fast with high separation
      efficiency. 

PMID- 27042250
TI  - The filament forming reactions of vimentin tetramers studied in a serial-inlet
      microflow device by small angle x-ray scattering.
AB  - The structural organization of metazoan cells and their shape are established
      through the coordinated interaction of a composite network consisting of three
      individual filament systems, collectively termed the cytoskeleton. Specifically,
      microtubules and actin filaments, which assemble from monomeric globular
      proteins, provide polar structures that serve motor proteins as tracks. In
      contrast, intermediate filaments (IFs) assemble from highly charged, extended
      coiled coils in a hierarchical assembly mechanism of lateral and longitudinal
      interaction steps into non-polar structures. IF proteins are expressed in a
      distinctly tissue-specific way and thereby serve to generate the precise
      plasticity of the respective cells and tissues. Accordingly, in the cell,
      numerous parameters such as pH and salt concentration are adjusted such that the
      generation of functional networks is ensured. Here, we transfer the problem for
      the mesenchymal IF protein vimentin to an in vitro setting and combine small
      angle x-ray scattering with microfluidics and finite element method simulations.
      Our approach is adapted to resolve the early assembly steps, which take place in
      the sub-second to second range. In particular, we reveal the influence of ion
      species and concentrations on the assembly. By tuning the flow rates and thus
      concentration profiles, we find a minimal critical salt concentration for the
      initiation of the assembly. Furthermore, our analysis of the surface sensitive
      Porod regime in the x-ray data reveals that the formation of first assembly
      intermediates, so-called unit length filaments, is not a one-step reaction but
      consists of distinct consecutive lateral association steps followed by radial
      compaction as well as smoothening of the surface of the full-width filament. 

PMID- 27042251
TI  - A multiplexed immunoaggregation biomarker assay using a two-stage micro resistive
      pulse sensor.
AB  - We present an immunoaggregation assay chip for multiplexed biomarkers detection.
      This chip is based on immunoaggregation of antibody functionalized microparticles
      (Ab-MPs) to quantify concentrations of multiple biomarkers simultaneously. A
      mixture of multiple types of Ab-MPs probes with different sizes and magnetic
      properties, which were functionalized by different antibodies, was used for the
      multiplexed assay. The interactions between biomarkers and their specific Ab-MPs
      probes caused the immunoaggregation of Ab-MPs. A two-stage micro resistive pulse
      sensor was used to differentiate and count the Ab-MP aggregates triggered by
      different biomarkers via size and magnetic property for multiplexed detection.
      The volume fraction of each type of Ab-MP aggregates indicates the concentration
      of the corresponding target biomarker. In our study, we demonstrated multiplexed
      detection of two model biomarkers (human ferritin and mouse anti-rabbit IgG) in
      10% fetal bovine serum, using anti-ferritin Ab and anti-mouse IgG Ab
      functionalized MPs. We found that the volume fraction of Ab-MP aggregates
      increased with the increased biomarker concentrations. The detection ranges from
      5.2 ng/ml to 208 ng/ml and 3.1 ng/ml to 5.12 * 10(4 )ng/ml were achieved for
      human ferritin and mouse anti-rabbit IgG. This bioassay chip is able to
      quantitatively detect multiple biomarkers in a single test without fluorescence
      or enzymatic labeling process and hence is promising to serve as a useful tool
      for rapid detection of multiple biomarkers in biomedical research and clinical
      applications. 

PMID- 27042252
TI  - Low-cost, disposable microfluidics device for blood plasma extraction using
      continuously alternating paramagnetic and diamagnetic capture modes.
AB  - Blood plasma contains biomarkers and substances that indicate the physiological
      state of an organism, and it can be used to diagnose various diseases or body
      condition. To improve the accuracy of diagnostic test, it is required to obtain
      the high purity of blood plasma. This paper presents a low-cost, disposable
      microfluidics device for blood plasma extraction using magnetophoretic behaviors
      of blood cells. This device uses alternating magnetophoretic capture modes to
      trap and separate paramagnetic and diamagnetic cells away from blood plasma. The
      device system is composed of two parts, a disposable microfluidics chip and a non
      disposable (reusable) magnetic field source. Such modularized device helps the
      structure of the disposable part dramatically simplified, which is beneficial for
      low-cost mass production. A series of numerical simulation and parametric study
      have been performed to describe the mechanism of blood cell separation in the
      microchannel, and the results are discussed. Furthermore, experimental
      feasibility test has been carried out in order to demonstrate the blood plasma
      extraction process of the proposed device. In this experiment, pure blood plasma
      has been successfully extracted with yield of 21.933% from 75 MUl 1:10 dilution
      of deoxygenated blood. 

PMID- 27042253
TI  - Reconstructing transmission trees for communicable diseases using densely sampled
      genetic data.
AB  - Whole genome sequencing of pathogens from multiple hosts in an epidemic offers
      the potential to investigate who infected whom with unparalleled resolution,
      potentially yielding important insights into disease dynamics and the impact of
      control measures. We considered disease outbreaks in a setting with dense genomic
      sampling, and formulated stochastic epidemic models to investigate person-to
      person transmission, based on observed genomic and epidemiological data. We
      constructed models in which the genetic distance between sampled genotypes
      depends on the epidemiological relationship between the hosts. A data augmented
      Markov chain Monte Carlo algorithm was used to sample over the transmission
      trees, providing a posterior probability for any given transmission route. We
      investigated the predictive performance of our methodology using simulated data,
      demonstrating high sensitivity and specificity, particularly for rapidly mutating
      pathogens with low transmissibility. We then analyzed data collected during an
      outbreak of methicillin-resistant Staphylococcus aureus in a hospital,
      identifying probable transmission routes and estimating epidemiological
      parameters. Our approach overcomes limitations of previous methods, providing a
      framework with the flexibility to allow for unobserved infection times, multiple
      independent introductions of the pathogen, and within-host genetic diversity, as
      well as allowing forward simulation.

PMID- 27042254
TI  - [Introduction to the Dossier - The Mentoring Process and the Professional
      Development of College Students].

PMID- 27042255
TI  - MIRADA A LA MENTORIA EN INVESTIGACION DESDE LA PERSPECTIVA SOCIOCULTURAL DE
      VYGOTSKY.
AB  - In this article the authors illustrate the mentoring process through the
      framework of Vygotsky's sociocultural perspective regarding education and human
      development. To achieve this goal, they describe their experience as mentor and
      mentees in a research training mentoring program for undergraduate students. The
      authors argue that this theoretical and philosophical perspective offers a solid
      background to mentoring as a real option that contributes to the learning
      process. They recommend these programs to be encouraged by academic institutions
      in order for more students and professors to benefit from this process.

PMID- 27042256
TI  - Computer modeling of ischemic stroke.

PMID- 27042257
TI  - Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are
      Associated with Somatic Mutation Loads in Human Cancer.
AB  - The effects of abnormalities in the DNA glycosylases NEIL1, NEIL2, and NEIL3 on
      human cancer have not been fully elucidated. In this paper, we found that the
      median somatic total mutation loads and the median somatic single nucleotide
      mutation loads exhibited significant inverse correlations with the median NEIL1
      and NEIL2 expression levels and a significant positive correlation with the
      median NEIL3 expression level using data for 13 cancer types from the Cancer
      Genome Atlas (TCGA) database. A subset of the cancer types exhibited reduced
      NEIL1 and NEIL2 expressions and elevated NEIL3 expression, and such abnormal
      expressions of NEIL1, NEIL2, and NEIL3 were also significantly associated with
      the mutation loads in cancer. As a mechanism underlying the reduced expression of
      NEIL1 in cancer, the epigenetic silencing of NEIL1 through promoter
      hypermethylation was found. Finally, we investigated the reason why an elevated
      NEIL3 expression level was associated with an increased number of somatic
      mutations in cancer and found that NEIL3 expression was positively correlated
      with the expression of APOBEC3B, a potent inducer of mutations, in diverse
      cancers. These results suggested that the abnormal expressions of NEIL1, NEIL2,
      and NEIL3 are involved in cancer through their association with the somatic
      mutation load. 

PMID- 27042258
TI  - Magnesium Supplementation Diminishes Peripheral Blood Lymphocyte DNA Oxidative
      Damage in Athletes and Sedentary Young Man.
AB  - Sedentary lifestyle is highly associated with increased risk of cardiovascular
      disease, obesity, and type 2 diabetes. It is known that regular physical activity
      has positive effects on health; however several studies have shown that acute and
      strenuous exercise can induce oxidative stress and lead to DNA damage. As
      magnesium is essential in maintaining DNA integrity, the aim of this study was to
      determine whether four-week-long magnesium supplementation in students with
      sedentary lifestyle and rugby players could prevent or diminish impairment of
      DNA. By using the comet assay, our study demonstrated that the number of
      peripheral blood lymphocytes (PBL) with basal endogenous DNA damage is
      significantly higher in rugby players compared to students with sedentary
      lifestyle. On the other hand, magnesium supplementation significantly decreased
      the number of cells with high DNA damage, in the presence of exogenous H2O2, in
      PBL from both students and rugby players, and markedly reduced the number of
      cells with medium DNA damage in rugby players compared to corresponding control
      nonsupplemented group. Accordingly, the results of our study suggest that four
      week-long magnesium supplementation has marked effects in protecting the DNA from
      oxidative damage in both rugby players and in young men with sedentary lifestyle.
      Clinical trial is registered at ANZCTR Trial Id: ACTRN12615001237572. 

PMID- 27042259
TI  - Endogenous Generation of Singlet Oxygen and Ozone in Human and Animal Tissues:
      Mechanisms, Biological Significance, and Influence of Dietary Components.
AB  - Recent studies have shown that exposing antibodies or amino acids to singlet
      oxygen results in the formation of ozone (or an ozone-like oxidant) and hydrogen
      peroxide and that human neutrophils produce both singlet oxygen and ozone during
      bacterial killing. There is also mounting evidence that endogenous singlet oxygen
      production may be a common occurrence in cells through various mechanisms. Thus,
      the ozone-producing combination of singlet oxygen and amino acids might be a
      common cellular occurrence. This paper reviews the potential pathways of
      formation of singlet oxygen and ozone in vivo and also proposes some new pathways
      for singlet oxygen formation. Physiological consequences of the endogenous
      formation of these oxidants in human tissues are discussed, as well as examples
      of how dietary factors may promote or inhibit their generation and activity. 

PMID- 27042260
TI  - Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption
      of High Fructose Corn Syrup in Rats.
AB  - Fructose corn syrup is cheap sweetener and prolongs the shelf life of products,
      but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and
      hypertension. All of them are referred to as metabolic syndrome and they are risk
      factors for cardiovascular diseases. Hence, the harmful effects of increased
      fructose intake on health and their prevention should take greater consideration.
      Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome
      and vascular function which is important in the prevention of cardiovascular
      disease. However, there are no known studies about the effect of CAPE on fructose
      induced vascular dysfunction. In this study, we examined the effect of CAPE on
      vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30%
      fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50
      micromol/kg i.p. for the last two weeks) effectively restored this problem.
      Additionally, hypertension in HFCS-fed rats was also decreased in CAPE
      supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in
      blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial
      nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in
      contrast CAPE supplementation efficiently increased its production. The presented
      results showed that HFCS-induced cardiovascular abnormalities could be prevented
      by CAPE treatment. 

PMID- 27042261
TI  - Phlorizin, an Active Ingredient of Eleutherococcus senticosus, Increases
      Proliferative Potential of Keratinocytes with Inhibition of MiR135b and Increased
      Expression of Type IV Collagen.
AB  - E. senticosus extract (ESE), known as antioxidant, has diverse pharmacologic
      effects. It is also used as an antiaging agent for the skin and phlorizin (PZ) is
      identified as a main ingredient. In this study, the effects of PZ on epidermal
      stem cells were investigated. Cultured normal human keratinocytes and skin
      equivalents are used to test whether PZ affects proliferative potential of
      keratinocytes and how it regulates these effects. Skin equivalents (SEs) were
      treated with ESE and the results showed that the epidermis became slightly
      thickened on addition of 0.002% ESE. The staining intensity of p63 as well as
      proliferating cell nuclear antigen (PCNA) is increased, and integrin alpha6 was
      upregulated. Analysis of ESE confirmed that PZ is the main ingredient. When SEs
      were treated with PZ, similar findings were observed. In particular, the
      expression of integrin alpha6, integrin beta1, and type IV collagen was
      increased. Levels of mRNA for type IV collagen were increased and levels of
      miR135b were downregulated. All these findings suggested that PZ can affect the
      proliferative potential of epidermal cells in part by microenvironment changes
      via miR135b downregulation and following increased expression of type IV
      collagen. 

PMID- 27042262
TI  - Genome sequence of Shimia str. SK013, a representative of the Roseobacter group
      isolated from marine sediment.
AB  - Shimia strain SK013 is an aerobic, Gram-negative, rod shaped alphaproteobacterium
      affiliated with the Roseobacter group within the family Rhodobacteraceae. The
      strain was isolated from surface sediment (0-1 cm) of the Skagerrak at 114 m
      below sea level. The 4,049,808 bp genome of Shimia str. SK013 comprises 3,981
      protein-coding genes and 47 RNA genes. It contains one chromosome and no
      extrachromosomal elements. The genome analysis revealed the presence of genes for
      a dimethylsulfoniopropionate lyase, demethylase and the trimethylamine
      methyltransferase (mttB) as well as genes for nitrate, nitrite and dimethyl
      sulfoxide reduction. This indicates that Shimia str. SK013 is able to switch from
      aerobic to anaerobic metabolism and thus is capable of aerobic and anaerobic
      sulfur cycling at the seafloor. Among the ability to convert other sulfur
      compounds it has the genetic capacity to produce climatically active dimethyl
      sulfide. Growth on glutamate as a sole carbon source results in formation of cell
      connecting filaments, a putative phenotypic adaptation of the surface-associated
      strain to the environmental conditions at the seafloor. Genome analysis revealed
      the presence of a flagellum (fla1) and a type IV pilus biogenesis, which is
      speculated to be a prerequisite for biofilm formation. This is also related to
      genes responsible for signalling such as N-acyl homoserine lactones, as well as
      quip-genes responsible for quorum quenching and antibiotic biosynthesis. Pairwise
      similarities of 16S rRNA genes (98.56 % sequence similarity to the next relative
      S. haliotis) and the in silico DNA-DNA hybridization (21.20 % sequence similarity
      to S. haliotis) indicated Shimia str. SK013 to be considered as a new species.
      The genome analysis of Shimia str. SK013 offered first insights into specific
      physiological and phenotypic adaptation mechanisms of Roseobacter-affiliated
      bacteria to the benthic environment. 

PMID- 27042263
TI  - Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism
      and contributing factors.
AB  - It is possible that SGLT2 inhibitors trigger euglycemic diabetic ketoacidosis in
      some patients. Possible mechanism of euglycemic DKA induced by SGLT2 inhibitors
      is illustrated. 

PMID- 27042264
TI  - Genetics of cardiovascular and renal complications in diabetes.
AB  - The development of debilitating complications represents a major healthcare
      burden associated with the treatment of diabetes. Despite advances in new
      therapies for controlling hyperglycemia, the burden associated with diabetic
      complications remains high, especially in relation to cardiovascular and renal
      complications. Furthermore, an increasing proportion of patients develop type 2
      diabetes at a younger age, putting them at higher risk of developing
      complications as a result of the increased exposure to hyperglycemia. Diabetes
      has become the main contributing cause to end-stage renal disease in most
      countries. Although there has been important breakthroughs in our understanding
      of the genetics of type 1 and type 2 diabetes, bringing important insights
      towards the pathogenesis of diabetes, there has been comparatively less progress
      in our understanding of the genetic basis of diabetic complications. Genome-wide
      association studies are beginning to expand our understanding of the genetic
      architecture relating to diabetic complications. Improved understanding of the
      genetic basis of diabetic cardiorenal complications might provide an opportunity
      for improved risk prediction, as well as the development of new therapies.

PMID- 27042265
TI  - Dynamic pathology of islet endocrine cells in type 2 diabetes: beta-Cell growth,
      death, regeneration and their clinical implications.
AB  - Diabetes is defined as a disease of hyperglycemic metabolic disorder caused by
      impaired insulin action or low insulin secretion, resulting in the occurrence of
      vascular complications. Based on this definition, diabetes therapy has long been
      oriented to correct hyperglycemia against the specific complications of diabetes.
      This definition has posed some difficulties, however, in understanding of the
      pathophysiology of this complicated disease and as such in the establishment of
      an effective treatment. With continuing efforts to explore the structural basis
      for diabetes onset and methodological development of immunohistochemistry,
      progressive decline of beta-cells is now established as a salient feature of type
      2 diabetes. Accordingly, diabetes therapy has now turned out to protect beta
      cells concurrently with the correction of hyperglycemia. Together with this
      effort, exploration of the means to regenerate beta-cells or to supply new beta
      cells by, for example, induced pluripotential stem cells, are vigorously made
      with the search for the mechanism of beta-cell decline in diabetes. In the
      present review, we describe the advances in the islet pathology in type 2
      diabetes with special reference to the dynamic alterations of islet endocrine
      cells in the milieu of maturation, obesity, aging and ethnic differences. The
      effect of amyloid deposition is also discussed. We hope it will help with
      understanding the pathophysiology of diabetes, and suggest the future direction
      of diabetes treatment. 

PMID- 27042266
TI  - Control of intestinal stem cell fate: A novel approach to treating diabetes.
AB  - Targeting L-cell development and enrichment of incretin-secreting cells could
      potentially evolve as novel, effective therapeutics for diabetes. 

PMID- 27042267
TI  - Autophagy: Starved beta-cells seem different from starved body.

PMID- 27042268
TI  - Src regulates insulin secretion and glucose metabolism by influencing subcellular
      localization of glucokinase in pancreatic beta-cells.
AB  - AIMS/INTRODUCTION: Src, a non-receptor tyrosine kinase, regulates a wide range of
      cellular functions, and hyperactivity of Src is involved in impaired glucose
      metabolism in pancreatic beta-cells. However, the physiological role of Src in
      glucose metabolism in normal, unstressed beta-cells remains unclear. In the
      present study, we investigated the role of Src in insulin secretion and glucose
      metabolism. MATERIALS AND METHODS: Src was downregulated using small interfering
      ribonucleic acid in INS-1 cells, and glucose-induced insulin secretion, adenosine
      triphosphate content, intracellular calcium concentration, glucose utilization
      and glucokinase activity were measured. Expression levels of messenger
      ribonucleic acid and protein of glucokinase were examined by semiquantitative
      real-time polymerase chain reaction and immunoblotting, respectively. Cells were
      fractionated by digitonin treatment, and subcellular localization of glucokinase
      was examined by immunoblotting. Interaction between glucokinase and neuronal
      nitric oxide synthase was estimated by immunoprecipitation. RESULTS: In Src
      downregulated INS-1 cells, glucose-induced insulin secretion was impaired,
      whereas insulin secretion induced by high K(+) was not affected. Intracellular
      adenosine triphosphate content and elevation of intracellular calcium
      concentration by glucose stimulation were suppressed by Src downregulation. Src
      downregulation reduced glucose utilization in the presence of high glucose, which
      was accompanied by a reduction in glucokinase activity without affecting its
      expression. However, Src downregulation reduced glucokinase in soluble,
      cytoplasmic fraction, and increased it in pellet containing intaracellular
      organelles. In addition, interaction between glucokinase and neuronal nitric
      oxide synthase was facilitated by Src downregulation. CONCLUSIONS: Src plays an
      important role in glucose-induced insulin secretion in pancreatic beta-cells
      through maintaining subcellular localization and activity of glucokinase.

PMID- 27042269
TI  - Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic
      glucose, lipid profiles and insulin sensitivity in high-fat diet-fed mice by
      modulating expression of genes in peroxisome proliferator-activated receptor
      signaling pathway.
AB  - AIMS/INTRODUCTION: Uncoupling protein 2 (UCP2), which was an important
      mitochondrial inner membrane protein associated with glucose and lipid
      metabolism, widely expresses in all kinds of tissues including hepatocytes. The
      present study aimed to explore the impact of UCP2 deficiency on glucose and lipid
      metabolism, insulin sensitivity and its effect on the liver-associated signaling
      pathway by expression profiling analysis. MATERIALS AND METHODS: Four-week-old
      male UCP2-/- mice and UCP2+/+ mice were randomly assigned to four groups: UCP2-/-
      on a high-fat diet, UCP2-/- on a normal chow diet, UCP2+/+ on a high-fat diet and
      UCP2+/+ on a normal chow diet. The differentially expressed genes in the four
      groups on the 16th week were identified by Affymetrix gene array. RESULTS: The
      results of intraperitoneal glucose tolerance test and insulin tolerance showed
      that blood glucose and beta-cell function were improved in the UCP2-/- group on
      high-fat diet. Enhanced insulin sensitivity was observed in the UCP2-/- group.
      The differentially expressed genes were mapped to 23 pathways (P < 0.05). We
      concentrated on the 'peroxisome proliferator-activated receptor (PPAR) signaling
      pathway' (P = 3.19 * 10(-11)), because it is closely associated with the
      regulation of glucose and lipid profiles. In the PPAR signaling pathway, seven
      genes (PPARgamma, Dbi, Acsl3, Lpl, Me1, Scd1, Fads2) in the UCP2-/- mice were
      significantly upregulated. CONCLUSIONS: The present study used gene arrays to
      show that activity of the PPAR signaling pathway involved in the improvement of
      glucose and lipid metabolism in the liver of UCP2-deficient mice on a long-term
      high-fat diet. The upregulation of genes in the PPAR signaling pathway could
      explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The
      manipulation of UCP2 protein expression could represent a new strategy for the
      prevention and treatment of diabetes.

PMID- 27042270
TI  - Association of salivary alpha 2-macroglobulin levels and clinical characteristics
      in type 2 diabetes.
AB  - AIMS/INTRODUCTION: Studies suggest that salivary proteins can be used as
      potential non-invasive markers for clinical diagnosis and screening for diabetes.
      Previous reports showed that plasma alpha 2-macroglobulin (A2MG) levels were
      higher in diabetic patients, especially with diabetic complications. We
      investigated the relationship between salivary A2MG values and clinical
      characteristics in patients with type 2 diabetes. MATERIALS AND METHODS: A total
      of 91 adults were recruited from our outpatient clinics. The study the patients'
      collected general and biochemical data, and blood glucose (fasting glucose,
      glycated hemoglobin [HbA1c]) data. Plasma and salivary A2MG levels were examined
      by enzyme-linked immunosorbent assay. RESULTS: The salivary A2MG levels were
      significantly positively correlated with plasma A2MG levels, fasting glucose
      HbA1c and periodontitis status. After 3 months of follow up, the net change of
      salivary A2MG values positively correlated with the net change of fasting
      glucose, HbA1c and triglyceride levels, but negatively correlated with high
      density lipoprotein cholesterol changes. Furthermore, the correlations between
      salivary A2MG and fasting glucose HbA1c were better than plasma A2MG,
      respectively. CONCLUSIONS: Our data show that salivary A2MG levels have better
      correlation with fasting glucose HbA1c and periodontitis status than plasma A2MG
      in diabetic patients. Salivary A2MG concentration might serve as a non-invasive
      marker for clinical diabetic control.

PMID- 27042271
TI  - Influence of atherosclerosis-related risk factors on serum high-sensitivity C
      reactive protein levels in patients with type 2 diabetes: Comparison of their
      influence in obese and non-obese patients.
AB  - AIMS/INTRODUCTION: Increased levels of high-sensitivity C-reactive protein (hs
      CRP) likely leads to the development of atherosclerosis. Therefore, it is very
      important to know which factors largely influence hs-CRP levels. In the present
      study, we examined the influence of various atherosclerosis-related factors on hs
      CRP levels in patients with type 2 diabetes. MATERIALS AND METHODS: A total of
      275 patients (176 men, 99 women) were enrolled in this study. We tested the
      relationship between the number of risk factors reaching a desired value and hs
      CRP levels. The Mann-Whitney U-test was used to compare two groups. The Kruskal
      Wallis test was used to carry out overall group comparisons, and the Steel-Dwass
      test was used to carry out between-group comparisons. Spearman's rank correlation
      was carried out to study the correlation between hs-CRP levels and clinical
      parameters. Multivariate regression method was used to analyze the factors
      independently contributing to hs-CRP levels. RESULTS: Hs-CRP levels were lower in
      patients with a larger number of risk factors reaching a desired value. In
      particular, triglyceride and body mass index (BMI) were independent risk factors
      determining hs-CRP levels in a multivariate regression analysis. Furthermore, we
      compared the influence of various factors on hs-CRP levels in both obese (BMI
      >=25 kg/m(2)) and non-obese patients with type 2 diabetes (BMI <25 kg/m(2)). In
      obese groups, BMI and urinary albumin were independent risk factors determining
      hs-CRP levels, whereas triglyceride and statin were independent risk factors in
      non-obese patients. CONCLUSIONS: There is some difference in the factors
      responsible for hs-CRP levels in obese and non-obese patients with type 2
      diabetes.

PMID- 27042272
TI  - New risk-scoring system including non-alcoholic fatty liver disease for
      predicting incident type 2 diabetes in East China: Shanghai Baosteel Cohort.
AB  - AIMS/INTRODUCTION: The present study aimed to explore the incidence of type 2
      diabetes, and to develop a risk-scoring model for predicting diabetes among the
      adult health check-up population in East China. MATERIALS AND METHODS:
      Participants from the Shanghai Baosteel Cohort (age >=20 years) without diabetes
      at baseline were recruited in a 6-year follow-up study. In order to explore risk
      factors for diabetes, this cohort was categorized into two groups: new diabetes
      and no diabetes. Three models were developed by Cox regression analysis. The
      model accuracy was assessed using the area under the receiver operating
      characteristic curve. RESULTS: A total of 6,542 individuals were included in the
      Shanghai Baosteel Cohort Study. Of them, 368 (5.6%) developed type 2 diabetes at
      the end of the follow-up period. Cox regression analysis found a close
      association between incident type 2 diabetes and several risk factors including
      non-alcoholic fatty liver diseases at baseline. The Shanghai Baosteel Score
      including advanced age (2 points), hypertriglyceridemia (2 points), obesity (2
      points), non-alcoholic fatty liver diseases (2 points) and impaired fasting
      glucose (3 points) had a good diagnostic performance with estimated area under
      the receiver operating characteristic curve (0.724), sensitivity (57.9%) and
      specificity (72.2%) at a cut-off point of >3. CONCLUSIONS: A risk-scoring system
      including non-alcoholic fatty liver diseases can help identify individuals at a
      high risk of diabetes in the East Chinese population.

PMID- 27042273
TI  - Association of chemokine ligand 5/chemokine receptor 5 gene promoter
      polymorphisms with diabetic microvascular complications: A meta-analysis.
AB  - AIMS/INTRODUCTION: Chemokine ligand 5 (CCL5) is a member of the CC-chemokine
      family expressed in various organs. It contributes to the migration of
      monocytes/macrophages into injured vascular walls by binding with its receptor
      chemokine receptor 5 (CCR5). Many studies have accessed the association between
      CCL5/CCR5 gene promoter polymorphisms and diabetic microvascular complications
      (DMI). However, the results are conflicting and inconclusive. The aim of the
      present study was to evaluate the association more precisely. MATERIALS AND
      METHODS: Trials were retrieved through PubMed, Embase, Medline, China National
      Knowledge Infrastructure, Web of Science and Cochrane database without
      restrictions on language. The pooled odds ratio (OR) and 95% confidence interval
      (CI) were used to describe the strength of association with DMI. RESULTS: Data
      were obtained from 11 case-control studies that included 2,737 DMI patients and
      2,435 diabetic control subjects. In the overall analysis, the CCL5-403 G/A and
      CCL5-28 C/G gene polymorphisms were not significantly associated with the risk of
      DMI. However, CCR5-59029 G/A was an independent risk factor of DMI in a dominant
      model (OR 1.77, 95% CI 1.06-2.97). Subgroup analysis showed that the risk of the
      CCR5 59029A-positive genotype was significant in Asians (OR 2.08, 95% CI 1.68
      2.57). In addition, the CCR5 59029A-positive genotype was associated with
      increased risk of albuminuria. CONCLUSIONS: There were no associations of CCL5
      gene promoter polymorphism with the risk of DMI. However, the 59029A polymorphism
      in CCR5 might affect individual susceptibility for DMI.

PMID- 27042274
TI  - Phenotyping of type 2 diabetes mellitus at onset on the basis of fasting incretin
      tone: Results of a two-step cluster analysis.
AB  - AIMS/INTRODUCTION: According to some authors, in type 2 diabetes there is a
      reduced postprandial action of glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP). However, little is known about the
      role of fasting incretins in glucose homeostasis. Our aim was to evaluate,
      through a two-step cluster analysis, the possibility of phenotyping patients with
      type 2 diabetes at onset on the basis of fasting GLP-1, GIP and ghrelin.
      MATERIALS AND METHODS: A total of 96 patients with type 2 diabetes within 6
      months of onset (mean age 62.40 +/- 6.36 years) were cross-sectionally studied.
      Clinical, anthropometric and metabolic parameters were evaluated. At fasting the
      following were carried out: assay of GLP-1, GIP, ghrelin, insulin, C-peptide,
      glucagon and a panel of adipocytokines (visfatin, resistin, leptin, soluble
      leptin receptor and adiponectin). RESULTS: The analysis resulted in two clusters:
      cluster 1 (63 patients) had significantly lower levels of GLP-1 (4.93 +/- 0.98 vs
      7.81 +/- 1.98 pmol/L; P < 0.001), GIP (12.73 +/- 9.44 vs 23.88 +/- 28.56 pmol/L;
      P < 0.001) and ghrelin (26.54 +/- 2.94 vs 39.47 +/- 9.84 pmol/L; P < 0.001)
      compared with cluster 2 (33 patients). Between the two clusters, no differences
      in age, duration of disease, sex, clinical-anthropometric parameters, insulin
      sensitivity and adipocytokines were highlighted. However, cluster 1 was
      associated with significantly higher levels of glycated hemoglobin (7.4 +/- 0.61
      vs 6.68 +/- 0.57%, P = 0.007), glucagon (232.02 +/- 37.27 vs 183.33 +/- 97.29
      ng/L; P = 0.001), fasting glucose (7.85 +/- 1.60 vs 6.93 +/- 1.01 mmol/L; P =
      0.003) and significantly lower levels of C-peptide (0.12 +/- 0.11 vs 0.20 +/-
      0.20 nmol/L; P = 0.017). CONCLUSIONS: The present study suggests that fasting
      incretins play an important role in the pathophysiology of type 2 diabetes, which
      requires to further investigation.

PMID- 27042275
TI  - Effect of serum 25-hydroxyvitamin D3 on insulin resistance and beta-cell function
      in newly diagnosed type 2 diabetes patients.
AB  - AIMS/INTRODUCTION: To evaluate serum 25-hydroxyvitamin D3 (25(OH)D3) in newly
      diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D3
      with insulin resistance and beta-cell function. MATERIALS AND METHODS: A total of
      97 newly diagnosed type 2 diabetes patients and 69 healthy controls were
      recruited. Serum 25(OH)D3 was determined using high-pressure liquid
      chromatography. Insulin resistance was measured using a homeostasis model
      assessment of insulin resistance (HOMA-IR). beta-Cell function was determined
      using the HOMA beta-cell function index (HOMA-beta), early-phase insulin
      secretion index (DeltaI30/DeltaG30) and area under the insulin curve (AUCins).
      Correlation analysis was carried out using Pearson's correlation and multiple
      stepwise regression analysis. RESULTS: Serum 25(OH)D3 was much lower in patients
      with newly diagnosed type 2 diabetes (t = -13.00, P < 0.01), and the prevalence
      of hypovitaminosis 25(OH)D3 was 62.9% (61/97) in diabetic patients. Among the
      diabetic patients, patients with hypovitaminosis 25(OH)D3 showed higher
      glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA-beta,
      DeltaI30/DeltaG30 and AUCins. Serum 25(OH)D3 was independently positively
      correlated with DeltaI30/DeltaG30 and AUCins (P < 0.05), but was not
      significantly correlated with either HOMA-IR or HOMA-beta. Only triglycerides,
      glycosylated hemoglobin and DeltaI30/DeltaG30 emerged as independent factors
      associated with serum 25(OH)D3 in both diabetes patients and the health control
      group. CONCLUSIONS: The present results further showed a low serum 25(OH)D3
      concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D3
      deficiency is associated with disturbances in glucose metabolism and lipid
      metabolism. Serum 25(OH)D3 is not correlated with basal insulin resistance or
      beta-cell function, but is significantly positively correlated with glucose
      stimulated insulin secretion and beta-cell function.

PMID- 27042276
TI  - Difference between old and young adults in contribution of beta-cell function and
      sarcopenia in developing diabetes mellitus.
AB  - AIMS/INTRODUCTION: To investigate the difference in contributing factors in
      developing diabetes between old and young adults. MATERIALS AND METHODS: Subjects
      with recent-onset diabetes were selected from a nationwide survey data and
      classified according to age: elderly (age >=75 years), middle-age (age 45-64
      years) and young (age 25-39 years). The homeostasis model assessment of insulin
      resistance and beta-cell function were calculated. Sarcopenia was assessed using
      dual-energy X-ray absorptiometry. RESULTS: The prevalence of recent-onset
      diabetes was 13.5%, 8.0%, and 1.4% in patients aged >=75 years (unweighted n =
      1,082), 45-64 years (unweighted n = 6,532), and 25-39 years (unweighted n =
      5,178), respectively. Homeostasis model assessment of beta-cell function along
      with homeostasis model assessment of insulin resistance showed increasing trends
      as onset age increased in recent-onset diabetes (P for trend < 0.001 in both).
      Elderly-onset diabetic patients had significantly higher homeostasis model
      assessment of beta-cell function and homeostasis model assessment of insulin
      resistance compared with the middle-age-onset group (P < 0.001 and 0.014,
      respectively). Multivariate analysis showed that sarcopenia was significantly
      associated with recent-onset diabetes only in patients aged >=75 years (odds
      ratio [OR] 2.478, 95% confidence interval [CI] 1.379-4.452) but not in patients
      aged 45-64 years. In the middle-age group, abdominal obesity (OR 2.933, 95% CI
      2.086-4.122), hypertriglyceridemia (OR 1.529, 95% CI 1.078-2.169]) and low high
      density lipoprotein cholesterolemia (OR 1.930, 95% CI 1.383-2.695) were
      associated with recent-onset diabetes. CONCLUSIONS: Elderly-onset diabetic
      patients had higher insulin resistance and relatively preserved beta-cell
      function compared with middle-age-onset patients. Sarcopenia might play a more
      important role in developing diabetes in the elderly population.

PMID- 27042277
TI  - Independent association between glycated hemoglobin and arterial stiffness in
      healthy men.
AB  - AIMS/INTRODUCTION: Many studies have reported that high levels of glycated
      hemoglobin (HbA1c) are strongly associated with an increased risk of
      cardiovascular disease. Many researchers have not studied the association of
      HbA1c with various subclinical atherosclerosis phenotypes. We evaluated the
      impact of HbA1c on arterial stiffness and atherosclerosis in healthy Korean
      healthy men. MATERIALS AND METHODS: The study population included healthy adult
      men who participated in health check-ups. All participants fasted for at least 8
      h before taking the blood sample for fasting blood glucose, HbA1c, total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol and triglyceride. Arterial stiffness was measured using brachial
      ankle pulse wave velocity. Hierarchical regression analysis allowed us to
      determine the relationship between brachial-ankle pulse wave velocity (baPWV) and
      potential risk factors for cardiovascular disease. RESULTS: Age and HbA1c were
      significantly related to baPWV, in model 1. In model 2, blood pressure was added
      to model 1. Systolic blood pressure was a more significant variable, which was
      more affected on baPWV than diastolic blood pressure. In the case of model 3, we
      included all variables regarding arterial stiffness. According to model 3, the
      most explainable variable was age, and then systolic blood pressure, body mass
      index and triglyceride, respectively. CONCLUSIONS: We analyzed the associations
      between HbA1c, which is one of the risk factors, and arterial stiffness
      independently. An arterial stiffness measurement using baPWV can show the level
      of severity of the arteriosclerosis. When the level of stiffness has been
      increased, we could assume that the risk of arteriosclerosis would be increased.
      It can also be related to the increase of the risk of cardiovascular disease.

PMID- 27042278
TI  - Correlations of serum visfatin and metabolisms of glucose and lipid in women with
      gestational diabetes mellitus.
AB  - AIMS/INTRODUCTION: Visfatin is a newly discovered adipocytokine hormone, which
      exerts an insulin-like effect by binding to the insulin receptor-1. However, the
      role of visfatin in human gestational diabetes mellitus (GDM) remains
      controversial. The purpose of the present study was to investigate the
      correlation between serum visfatin and metabolism of glucose and lipid in GDM.
      MATERIALS AND METHODS: This was a prospective study. A total of 38 GDM patients
      and 35 age- and body mass index-matched controls were studied between January
      2012 and October 2013. Fasting serum levels of visfatin, fasting plasma glucose,
      hemoglobin A1c and lipid profile were measured. Two-tailed t-tests and Pearson's
      correlation coefficient were used to analyze the data. RESULTS: Perinatal
      visfatin levels were negatively correlated with fasting plasma glucose, insulin
      resistance index and triglycerides in controls (r = -0.47, -0.51, -0.57,
      respectively; P < 0.05), and positively correlated with high-density lipoprotein
      cholesterol (r = 0.32, P < 0.05). A positive correlation with visfatin level only
      appeared in weight gain and body mass index in women with GDM (r = 0.36, 0.45,
      respectively; P < 0.05). CONCLUSIONS: Visfatin appears to be involved in glucose
      and lipid metabolism regulation and insulin resistance, suggesting a role in GDM
      pathogenesis.

PMID- 27042279
TI  - Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus
      patients with blood glucose levels inadequately controlled by sitagliptin.
AB  - AIMS/INTRODUCTION: The aim of the present study was to evaluate the long-term
      efficacy and safety of adding repaglinide in patients with type 2 diabetes
      mellitus whose blood glucose levels were not sufficiently controlled by treatment
      with a dipeptidyl peptidase-4 inhibitor, sitagliptin, in addition to diet and
      exercise therapies. MATERIALS AND METHODS: This was a multicenter, uncontrolled,
      dose-titration study with a treatment period of 52 weeks. The primary end-point
      was the change in glycated hemoglobin levels from baseline. RESULTS: The glycated
      hemoglobin level was 7.43 +/- 0.57% (mean +/- standard deviation) at baseline,
      and decreased to 6.93 +/- 0.91% at the end of the study. The mean changes in
      glycated hemoglobin levels at 4 weeks and at the end of the study were -0.44 +/-
      0.28% and -0.50 +/- 0.82%, respectively. The glycated hemoglobin-lowering effect
      was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and
      there were 352 adverse events. The rate of adverse drug reactions was 21.0%
      (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no
      incidence of 'major hypoglycemia'. CONCLUSIONS: Combination therapy with
      repaglinide and sitagliptin was considered effective for a long term without
      clinical safety problems in patients with type 2 diabetes mellitus.

PMID- 27042280
TI  - Comparison of clinical characteristics in patients with type 2 diabetes among
      whom different antihyperglycemic agents were prescribed as monotherapy or
      combination therapy by diabetes specialists.
AB  - AIMS/INTRODUCTION: We compared clinical characteristics in patients with type 2
      diabetes for whom different antihyperglycemic agents were prescribed as
      monotherapy or combination therapy by diabetes specialists in Japan. MATERIALS
      AND METHODS: Prescription data for 2005, 2008 and 2011 from diabetes specialists'
      patient registries identified variables related to prescription of different
      antihyperglycemic agents. RESULTS: A total of 33,251 prescriptions in 2005,
      25,119 in 2008 and 20,631 in 2011 were analyzed. Prescribing insulin was related
      to younger age, long duration of diabetes and glycated hemoglobin (HbA1c) >=8.0%,
      but was negatively associated with obesity. Prescribing sulfonylureas was related
      to older age and long duration of diabetes, but not to obesity. Use of biguanides
      was related to younger age, short duration of diabetes and obesity, but was
      negatively associated with HbA1c >=8.0%. A short duration of diabetes and HbA1c
      >=8.0% were associated with use of a DPP-4 inhibitor, but not with obesity.
      Prescribing GLP-1 receptor agonists was related to younger age, obesity and HbA1c
      >=8.0%. Odds ratios for each antihyperglycemic combination therapy were
      determined based on the characteristics of each included antihyperglycemic agent.
      CONCLUSIONS: These results could be expected to reflect in part the consensus of
      diabetes specialists, and might provide guidance regarding pharmacotherapy in the
      clinical setting.

PMID- 27042281
TI  - Pharmacokinetic and pharmacodynamic properties of insulin degludec in Japanese
      patients with type 1 diabetes mellitus reflect similarities with Caucasian
      patients.
AB  - INTRODUCTION: The present study aimed to evaluate the pharmacokinetic and
      pharmacodynamic properties of insulin degludec (IDeg) in Japanese patients with
      type 1 diabetes. MATERIALS AND METHODS: This was a randomized, single-center,
      double-blind, two-period, crossover, multiple-dose trial. Patients were
      randomized into two treatment sequences, and received IDeg or insulin detemir for
      6 days and a washout period (7-21 days) before switching treatment. Blood samples
      for pharmacokinetic measurements were obtained before each dose and up to 120 h
      after the last dose of each treatment period. Pharmacodynamic measurements were
      obtained using a 26-h euglycemic clamp procedure after the last dose of each
      treatment period. RESULTS: A total of 22 patients were randomized (14 men, 8
      women; mean glycosylated hemoglobin at baseline of 7.5% [based on Japanese
      Diabetes Society value]). At steady state, total glucose-lowering effect (area
      under the glucose infusion rate [GIR] curve during one dosing interval [tau, 0-24
      h] at steady state [AUCGIR ,tau, SS]) was 1,446 mg/kg and total exposure
      (geometric mean) of IDeg (AUCID eg,tau, SS) was 81,270 pmol h/L. Both the glucose
      lowering effect and the exposure of IDeg were evenly distributed over the dosing
      interval, with AUC for the first 12-h intervals being approximately 50% of the
      total (geometric mean; AUCGIR ,0-12h, SS/AUCGIR ,tau, SS = 48%; AUCID eg,0-12h,
      SS/AUCID eg,tau, SS = 53%). CONCLUSIONS: IDeg has a flat, consistent and ultra
      long glucose-lowering effect that is evenly distributed across a 24-h interval
      and an ultra-long duration of action in Japanese patients with type 1 diabetes.
      These data support once-daily dosing of IDeg in all patients. Overall, the
      pharmacodynamic and pharmacokinetic end-points and safety observations are
      consistent with those previously reported in Caucasian patients.

PMID- 27042282
TI  - Case of anal fistula with Fournier's gangrene in an obese type 2 diabetes
      mellitus patient.
AB  - A 64-year-old man was admitted to Shin-suma General Hospital, Kobe, Japan,
      complaining of a 3-day history of scrotal swelling and high fever. He had type 2
      diabetes mellitus. On examination, his body temperature had risen to 38.5 
      degrees C. Examination of the scrotum showed abnormal enlargement. Laboratory
      data were as follows: white cell count 35,400/MUL and glycated hemoglobin 9.6%.
      Anal fistula was found in an endorectal ultrasound. Computed tomography scan
      showed a relatively high density of subcutaneous tissue and elevated air density.
      Thus, he was diagnosed with Fournier's gangrene. On the fourth hospital day, the
      patient underwent debridement of gangrenous tissue. Seton surgery was carried out
      for anal fistula on the 34th hospital day. He responded to the treatment very
      well. He was discharged on the 33rd postoperative day. Once Fournier's gangrene
      has been diagnosed, considering the association of anal fistula and perianal
      abscess is important.

PMID- 27042283
TI  - Erratum.

PMID- 27042284
TI  - Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and
      increased parvalbumin-positive cortical interneuron density.
AB  - BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly
      conserved in vertebrates, and continuously expressed in the neocortex,
      hippocampus, olfactory bulb and cerebellum from mid-embryonic development through
      to adulthood. METHODS: Brinp1 knock-out (Brinp1(-/-)) mice were generated by Cre
      recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were
      characterised by behavioural phenotyping, immunohistochemistry and expression
      analysis of the developing and adult brain. RESULTS: Absence of Brinp1 during
      development results in a behavioural phenotype resembling autism spectrum
      disorder (ASD), in which knock-out mice show reduced sociability and changes in
      vocalisation capacity. In addition, Brinp1(-/-) mice exhibit hyper-locomotor
      activity, have impaired short-term memory, and exhibit poor reproductive success.
      Brinp1(-/-) mice show increased density of parvalbumin-expressing interneurons in
      the adult mouse brain. Brinp1(-/-) mice do not show signs of altered neural
      precursor proliferation or increased apoptosis during late embryonic brain
      development. The expression of the related neuronal migration genes Astn1 and
      Astn2 is increased in the brains of Brinp1(-/-) mice, suggesting that they may
      ameliorate the effects of Brinp1 loss. CONCLUSIONS: Brinp1 plays an important
      role in normal brain development and function by influencing neuronal
      distribution within the cortex. The increased cortical PV-positive interneuron
      density and altered behaviour of Brinp1(-/-) mice resemble features of a subset
      of human neurological disorders; namely autism spectrum disorder (ASD) and the
      hyperactivity aspect of attention deficit hyperactivity disorder (ADHD).

PMID- 27042285
TI  - Genome-wide analysis of copy number variations identifies PARK2 as a candidate
      gene for autism spectrum disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental
      disorder with complex genetic underpinning in its etiology. Copy number
      variations (CNVs) as one of the genetic factors associated with ASD have been
      addressed in recent genome-wide association studies (GWAS). However, the
      significance of CNV has not been well investigated in non-Caucasian ASD
      population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han
      Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093
      healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by
      focusing on case-specific CNVs. PARK2 was one of the important genes with several
      case-specific regions overlapped on it. The findings were validated in the
      initial screen sample set and replicated in another sample set by real-time
      quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned
      different exons of PARK2 were identified. The PARK2 expression level was down
      regulated at exon-dependent manner in cases with either deletion or duplication.
      The result revealed that the gene function might be disrupted by exonic deletion
      and duplication. We also observed that the ASD case with exonic duplication
      demonstrated a more severe interference of PARK2 expression and the clinical
      feature than the ones with deletion at the exons 2-4 of the PARK2 gene.
      CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2
      function might contribute to genetic etiology of a proportion of cases with ASD.
      The intriguing results of this work warrant further study on characterizing the
      functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00494754.

PMID- 27042286
TI  - Phase II Metabolic Pathways of Spectinamide Antitubercular Agents: A Comparative
      Study of the Reactivity of 4-Substituted Pyridines to Glutathione Conjugation.
AB  - Spectinamides are promising new semisynthetic anti-tubercular agents that are
      modified with a pyridyl side chain, which blocks native efflux from the
      tuberculosis cell. This study, describes the stability of an advanced panel of
      spectinamide analogs, with varying substitutions to the pyridyl side chain, to
      Phase-II conjugative metabolism by glucuronosyl transferase, sulfotransferase and
      glutathione-S-transferase enzymes using both human and rat S9 enzyme fractions.
      All solely 5-substituted pyridyl spectinamides exhibited complete stability
      towards Phase II conjugative enzymes. However, 4-chloro substituted pyridyl
      spectinamides were susceptible to glutathione conjugation with rates dependent on
      other substitutions to the pyridine ring. Electron donating 5-substitutions
      increased the propensity for glutathione conjugation and conversely the
      introduction of an electron withdrawing 5-fluoro group blocked all observed
      glutathione conjugation. Based on these Phase II metabolism studies, lead
      spectinamides 1329, 1445, 1599, 1661 and 1810 were found to have favorable
      properties for potential lead compounds with no Phase II liabilities.

PMID- 27042287
TI  - Webulous and the Webulous Google Add-On--a web service and application for
      ontology building from templates.
AB  - BACKGROUND: Authoring bio-ontologies is a task that has traditionally been
      undertaken by skilled experts trained in understanding complex languages such as
      the Web Ontology Language (OWL), in tools designed for such experts. As requests
      for new terms are made, the need for expert ontologists represents a bottleneck
      in the development process. Furthermore, the ability to rigorously enforce
      ontology design patterns in large, collaboratively developed ontologies is
      difficult with existing ontology authoring software. DESCRIPTION: We present
      Webulous, an application suite for supporting ontology creation by design
      patterns. Webulous provides infrastructure to specify templates for populating
      ontology design patterns that get transformed into OWL assertions in a target
      ontology. Webulous provides programmatic access to the template server and a
      client application has been developed for Google Sheets that allows templates to
      be loaded, populated and resubmitted to the Webulous server for processing.
      CONCLUSIONS: The development and delivery of ontologies to the community requires
      software support that goes beyond the ontology editor. Building ontologies by
      design patterns and providing simple mechanisms for the addition of new content
      helps reduce the overall cost and effort required to develop an ontology. The
      Webulous system provides support for this process and is used as part of the
      development of several ontologies at the European Bioinformatics Institute.

PMID- 27042288
TI  - Elaboration of bilateral symmetry across Knautia macedonica capitula related to
      changes in ventral petal expression of CYCLOIDEA-like genes.
AB  - BACKGROUND: Shifts in floral form across angiosperms, particularly from radially
      symmetrical to bilaterally symmetrical flowers, are often associated with shifts
      in speciation rates and changes in pollination syndrome. Growing evidence across
      both rosids and asterids indicates that CYCLOIDEA (CYC)-like transcription
      factors from the TCP gene family play a role in establishing the dorsoventral
      pattern of flower symmetry, which affects the development of both the corolla and
      androecium. Previous studies of CYC-like genes, especially of the CYC2 clade,
      indicate that these genes are dorsally restricted in bilaterally symmetrical
      flowers. Also, gene duplication of CYC-like genes often correlates with shifts in
      floral form in both individual flowers and head-like inflorescences (capitula).
      RESULTS: Here, we compared the expression patterns of six CYC-like genes from
      dorsal, lateral, and ventral petals of internal and external florets across
      capitula of Knautia macedonica (Dipsacaceae). We demonstrate that multiple copies
      of CYC-like genes are differentially expressed among petal types and between
      internal and external florets. Across paralogs, there was a general trend toward
      a reduction in dorsal expression and an increase in ventral expression in
      internal florets compared to external florets. However, it was in the ventral
      petals where a statistically significant increase in expression correlates with a
      less zygomorphic flower. We also show for the first time lateral-specific
      expression of a CYC-like gene. Additionally, dorsoventral asymmetric expression
      of a CYC3 paralog indicates that this understudied gene clade is likely also
      involved in floral symmetry. CONCLUSIONS: These data indicate that the
      elaboration of bilateral symmetry may be regulated by the dorsoventral gradient
      of expression, with statistically significant changes in ventral expression
      correlating with changes in dorsoventral morphological specialization.

PMID- 27042289
TI  - Expression profile of androgen-modulated microRNAs in the fetal murine lung.
AB  - BACKGROUND: Androgens are known to delay lung development. As a consequence, the
      incidence and morbidity of respiratory distress syndrome of the neonate are
      higher for male than for female premature infants. We previously reported that
      many genes were expressed with a sex difference in the mouse developing lung and
      that several genes were under the control of androgens in the male fetal lung.
      microRNAs are small non-coding RNAs known to negatively regulate the expression
      of specific genes. In this study, we examined whether murine miRNAs are under the
      control of androgens in the male developing lung. METHODS: Expression profiling
      of microRNAs was performed by microarrays using RNA extracted from male fetal
      lungs isolated on gestational day (GD) 17.0 and GD 18.0 after daily injection of
      pregnant mice from GD 10.0 with the antiandrogen flutamide or vehicle only. To
      identify putative miRNA target genes, the data obtained here were combined with
      gene profiling data reported previously using the same RNA preparations. qPCR was
      used to confirm microarray data with fetal lungs from other litters than those
      used in microarrays. RESULTS: Flutamide induced downregulation and upregulation
      of several miRNAs on GD 17.0 and GD 18.0. Of the 43 mature miRNAs modulated by
      flutamide on GD 17.0, 60 % were downregulated, whereas this proportion was only
      of 34 % for the 35 mature miRNAs modulated on GD 18.0. For 29 and 26 flutamide
      responsive miRNAs, we found a corresponding target inversely regulated by
      androgens on GD 17.0 and 18.0, respectively. The androgen-regulated target genes
      were involved in several biological processes (lipid metabolism, cell
      proliferation, and lung development) and molecular functions, mainly
      transcription factor binding. CONCLUSIONS: Regulation of male lung development
      involves several miRNAs that are under androgen modulation in vivo.

PMID- 27042290
TI  - Baicalein antagonizes acute megakaryoblastic leukemia in vitro and in vivo by
      inducing cell cycle arrest.
AB  - BACKGROUND: The prognosis of acute megakaryoblastic leukemia (AMKL) is really
      dismal, which urges for development of novel treatment. Baicalein is one type of
      flavonoids extracted from Scutellaria baicalensis Georgi (Huang Qin). It
      inhibited cell proliferation and subcutaneous tumor formation of many tumor cell
      lines. However, whether baicalein possesses anti-AMKL activities has not been
      tested. RESULTS: We found that baicalein potently inhibited proliferation of
      multiple AMKL cells including CMK, CMY, Y10, 6133, and 6133 MPL/W515L due to
      apoptosis and cell cycle arrest at G1 phase. Unexpectedly, caspase inhibitor z
      VAD-fmk did not restore cell proliferation. In contrast, ectopic expression of
      Cyclin D1 efficiently antagonized the inhibitory effect of baicalein. In
      addition, baicalein induced differentiation of 6133 MPL/W515L cells. Finally,
      baicalein promoted mice survival and reduced disease burden in a mouse model of
      AMKL. CONCLUSIONS: Baicalein possesses potent anti-AMKL activity in vitro and in
      vivo. Baicalein may be a potent reagent for AMKL therapy.

PMID- 27042292
TI  - The expression of CD123 can decrease with basophil activation: implications for
      the gating strategy of the basophil activation test.
AB  - BACKGROUND: Basophil activation test (BAT) reproduces IgE-mediated allergic
      reactions in vitro and has been used as a diagnostic test. Different markers can
      be used to identify basophils in whole blood and have implications for the
      outcome of the test. We aimed to assess changes in the expression of CD123 and
      HLA-DR following basophil activation and to select the best gating strategy for
      BAT using these markers. METHODS: BAT was performed in whole blood from 116
      children. Peanut extract, anti-IgE, anti-FcepsilonRI or formyl-methionyl-leucyl
      phenylalanin (fMLP) was used for stimulation. Surface expression of CD123, HLA
      DR, CD63 and CD203c was evaluated by flow cytometry. RESULTS: In some cases,
      gating on CD123+/HLA-DR- led to the loss-to-analysis of basophils in conditions
      where basophils were activated. Adding CD203c as an identification marker
      restored the cell number. Basophils remained HLA-DR-negative with activation.
      CD123 expression decreased following stimulation with fMLP (n = 116, p < 0.001),
      anti-IgE (n = 104, p < 0.001) and peanut (n = 42, p < 0.001). The decrease in the
      mean fluorescence intensity of CD123 correlated with the up-regulation of
      basophil activation markers, CD63 (rs = -0.31, p < 0.001) and CD203c (rs = -0.35,
      p < 0.001). BAT to peanut gating basophils on CD203c+/CD123+/HLA-DR- reduced the
      false-negatives (1 vs. 5 %) and showed a higher diagnostic accuracy compared to
      using CD123+/HLA-DR- (97 vs. 91 %). CD203c+ appeared as an alternative gating
      strategy allowing two-colour BAT. CONCLUSIONS: Basophils of a subset of patients
      down-regulate CD123 with activation. The use of CD203c before gating on
      CD123+/HLA-DR- cells or in isolation ensures the identification of the entire
      basophil population and accurate assessment of basophil activation, with
      important diagnostic implications.

PMID- 27042291
TI  - Efficient genome editing of genes involved in neural crest development using the
      CRISPR/Cas9 system in Xenopus embryos.
AB  - BACKGROUND: The RNA guided CRISPR/Cas9 nucleases have been proven to be effective
      for gene disruption in various animal models including Xenopus tropicalis. The
      neural crest (NC) is a transient cell population during embryonic development and
      contributes to a large variety of tissues. Currently, loss-of-function studies on
      NC development in X. tropicalis are largely based on morpholino antisense
      oligonucleotide. It is worthwhile establishing targeted gene knockout X.
      tropicails line using CRISPR/Cas9 system to study NC development. METHODS: We
      utilized CRISPR/Cas9 to disrupt genes that are involved in NC formation in X.
      tropicalis embryos. A single sgRNA and Cas9 mRNA synthesized in vitro, were co
      injected into X. tropicalis embryos at one-cell stage to induce single gene
      disruption. We also induced duplex mutations, large segmental deletions and
      inversions in X. tropicalis by injecting Cas9 and a pair of sgRNAs. The
      specificity of CRISPR/Cas9 was assessed in X. tropicalis embryos and the Cas9
      nickase was used to reduce the off-target cleavages. Finally, we crossed the G0
      mosaic frogs with targeted mutations to wild type frogs and obtained the germline
      transmission. RESULTS: Total 16 target sites in 15 genes were targeted by
      CRISPR/Cas9 and resulted in successful indel mutations at 14 loci with disruption
      efficiencies in a range from 9.3 to 57.8 %. Furthermore, we demonstrated the
      feasibility of generation of duplex mutations, large segmental deletions and
      inversions by using Cas9 and a pair of sgRNAs. We observed that CRISPR/Cas9
      displays obvious off-target effects at some loci in X. tropicalis embryos. Such
      off-target cleavages was reduced by using the D10A Cas9 nickase. Finally, the
      Cas9 induced indel mutations were efficiently passed to G1 offspring. CONCLUSION:
      Our study proved that CRISPR/Cas9 could mediate targeted gene mutation in X.
      tropicalis with high efficiency. This study expands the application of
      CRISPR/Cas9 platform in X. tropicalis and set a basis for studying NC development
      using genetic approach.

PMID- 27042293
TI  - Brainhack: a collaborative workshop for the open neuroscience community.
AB  - Brainhack events offer a novel workshop format with participant-generated content
      that caters to the rapidly growing open neuroscience community. Including
      components from hackathons and unconferences, as well as parallel educational
      sessions, Brainhack fosters novel collaborations around the interests of its
      attendees. Here we provide an overview of its structure, past events, and example
      projects. Additionally, we outline current innovations such as regional events
      and post-conference publications. Through introducing Brainhack to the wider
      neuroscience community, we hope to provide a unique conference format that
      promotes the features of collaborative, open science. 

PMID- 27042294
TI  - Biofilm formation, antimicrobial susceptibility, serogroups and virulence genes
      of uropathogenic E. coli isolated from clinical samples in Iran.
AB  - BACKGROUND: Uropathogenic Escherichia coli O- Serogroups with their virulence
      factors are the most prevalent causes of UTIs. The present research performed to
      track common uropathogenic E.coli serogroups, antibiotic resistance pattern of
      strains and prevalence of virulence genes in isolations having the ability to
      constitute biofilm. METHODS: In this research 130 E.coli isolation from patients
      having UTI symptoms were collected and antimicrobial resistance pattern was
      performed by Kirby-Bauer method. Polymerase chain reaction was done using primer
      pairs to identify common serogroups of uropathogenic E.coli and studying
      virulence genes in isolations creating biofilm. RESULTS: Among 130 E.coli
      isolates, 80 (61.53 %) were able to make biofilm that 15 isolates (18.75 %)
      indicated strong reaction, 20 (25 %) of medium and 45 (56.25 %) of weak biofilm
      reaction. Among isolations creating biofilm, the highest resistance reported to
      Ampicillin (87.5 %) and the lowest to Nitrofurantoin (3.75 %). The frequency of
      fimH, pap, sfa and afa genes in isolations having the ability to create strong
      biofilm reported 93.33 %, 86.66 %, 86.66 % and 66.66 %, respectively.
      CONCLUSIONS: The findings indicated the importance of virulence genes in
      serogroups producing uropathogenic E.coli biofilm. It is recommended that strains
      producing biofilm before antibiotic use should be studied.

PMID- 27042295
TI  - Amino acids and mammary gland development: nutritional implications for milk
      production and neonatal growth.
AB  - Milk is synthesized by mammary epithelial cells of lactating mammals. The
      synthetic capacity of the mammary gland depends largely on the number and
      efficiency of functional mammary epithelial cells. Structural development of the
      mammary gland occurs during fetal growth, prepubertal and post-pubertal periods,
      pregnancy, and lactation under the control of various hormones (particularly
      estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental
      lactogen, and prolactin) in a species- and stage-dependent manner. Milk is
      essential for the growth, development, and health of neonates. Amino acids (AA),
      present in both free and peptide-bound forms, are the most abundant organic
      nutrients in the milk of farm animals. Uptake of AA from the arterial blood of
      the lactating dam is the ultimate source of proteins (primarily beta-casein and
      alpha-lactalbumin) and bioactive nitrogenous metabolites in milk. Results of
      recent studies indicate extensive catabolism of branched-chain AA (leucine,
      isoleucine and valine) and arginine to synthesize glutamate, glutamine, alanine,
      aspartate, asparagine, proline, and polyamines. The formation of polypeptides
      from AA is regulated not only by hormones (e.g., prolactin, insulin and
      glucocorticoids) and the rate of blood flow across the lactating mammary gland,
      but also by concentrations of AA, lipids, glucose, vitamins and minerals in the
      maternal plasma, as well as the activation of the mechanistic (mammalian) target
      rapamycin signaling by certain AA (e.g., arginine, branched-chain AA, and
      glutamine). Knowledge of AA utilization (including metabolism) by mammary
      epithelial cells will enhance our fundamental understanding of lactation biology
      and has important implications for improving the efficiency of livestock
      production worldwide. 

PMID- 27042296
TI  - Gene expression of vascular endothelial growth factor A and hypoxic adaptation in
      Tibetan pig.
AB  - BACKGROUND: Vascular endothelial growth factor A (VEGFA) can induce endothelial
      cell proliferation, promote cell migration, and inhibit apoptosis. These
      processes play key roles in physiological blood vessel formation and pathological
      angiogenesis. METHODS: In this study, we examined VEGFA gene expression in the
      heart, liver, and kidney of Tibetan pigs (TP), Yorkshire pigs that migrated to
      high altitudes (YH), and Yorkshire pigs that lived at low altitudes (YL). We used
      PCR and Sanger sequencing to screen for single nucleotide polymorphisms (SNPs) in
      5'-flanking DNA and exons of the VEGFA gene. Quantitative real-time PCR and
      western blots were used to measure expression levels and PCR products were
      sequenced. RESULTS: Results showed that the VEGFA mRNA and protein expression in
      heart, liver and kidney of TP was higher than that in YH and YL. In addition, the
      mRNA sequence of the pig VEGFA gene was conserved among pig breeds, and only five
      SNPs were found in the 5'-flanking region of the VEGFA gene, the allele frequency
      distributions of the 5 SNPs were not significantly different between the TP,
      Yorkshire (YL), and Diannan small-ear (DN) pig populations. CONCLUSION: In
      conclusion, the Tibetan pig showed high levels of VEGFA gene expression in
      several hypoxic tissues, which suggests that the VEGFA gene may play a major
      functional role in hypoxic adaptation.

PMID- 27042297
TI  - Inhibition of fatty acid desaturation is detrimental to cancer cell survival in
      metabolically compromised environments.
AB  - BACKGROUND: Enhanced macromolecule biosynthesis is integral to growth and
      proliferation of cancer cells. Lipid biosynthesis has been predicted to be an
      essential process in cancer cells. However, it is unclear which enzymes within
      this pathway offer the best selectivity for cancer cells and could be suitable
      therapeutic targets. RESULTS: Using functional genomics, we identified stearoyl
      CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty
      acids, as essential in breast and prostate cancer cells. SCD inhibition altered
      cellular lipid composition and impeded cell viability in the absence of exogenous
      lipids. SCD inhibition also altered cardiolipin composition, leading to the
      release of cytochrome C and induction of apoptosis. Furthermore, SCD was required
      for the generation of poly-unsaturated lipids in cancer cells grown in spheroid
      cultures, which resemble those found in tumour tissue. We also found that SCD
      mRNA and protein expression is elevated in human breast cancers and predicts poor
      survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts
      efficiently blocked tumour growth and significantly increased animal survival.
      CONCLUSIONS: Our data implicate lipid desaturation as an essential process for
      cancer cell survival and suggest that targeting SCD could efficiently limit
      tumour expansion, especially under the metabolically compromised conditions of
      the tumour microenvironment.

PMID- 27042299
TI  - Inflammatory cytokine and humoral responses to Plasmodium falciparum
      glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis.
AB  - Pro-inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of
      Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally
      acquired anti-GPI antibody thought to provide protection against severe malaria
      (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the
      anti-GPI antibody levels increased with age in parallel with the development of
      acquired immunity, and high levels of anti-GPI antibodies were associated with
      mild malaria (MM) cases. In the present study, the relationship between the
      levels of pro-inflammatory cytokines and anti-GPI IgG antibody responses,
      parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM)
      patients. Sera from a total of 110 SM and 72 MM cases after excluding of
      ineligible patients were analyzed for the levels of anti-GPI antibodies, IgG
      subclasses, and cytokine responses by ELISA. While the total anti-GPI antibody
      levels were similar in overall SM and MM groups, they were significantly higher
      in surviving SM patients than in fatal SM cases. In the case of cytokines, the
      TNF-alpha and IL-6 levels were significantly higher in SM compared to MM, whereas
      the IL-10 levels were similar in both groups. The data presented here demonstrate
      that high levels of the circulatory pro-inflammatory, TNF-alpha, and IL-6, are
      indicators of malaria severity, whereas anti-inflammatory cytokine IL-10 level
      does not differentiate SM and MM cases. Further, among SM patients, relatively
      low levels of anti-GPI antibodies are indicators of fatal outcomes compared to
      survivors, suggesting that anti-GPI antibodies provide some level of protection
      against SM fatality. 

PMID- 27042298
TI  - The role of BST-2/Tetherin in host protection and disease manifestation.
AB  - Host cells respond to viral infections by activating immune response genes that
      are not only involved in inflammation, but may also predispose cells to cancerous
      transformation. One such gene is BST-2, a type II transmembrane protein with a
      unique topology that endows it tethering and signaling potential. Through this
      ability to tether and signal, BST-2 regulates host response to viral infection
      either by inhibiting release of nascent viral particles or in some models
      inhibiting viral dissemination. However, despite its antiviral functions, BST-2
      is involved in disease manifestation, a function linked to the ability of BST-2
      to promote cell-to-cell interaction. Therefore, modulating BST-2 expression
      and/or activity has the potential to influence course of disease. 

PMID- 27042300
TI  - Differential changes in gene expression in human neutrophils following TNF-alpha
      stimulation: Up-regulation of anti-apoptotic proteins and down-regulation of
      proteins involved in death receptor signaling.
AB  - Responses of human neutrophils to TNF-alpha are complex and multifactorial.
      Exposure of human neutrophils to TNF-alpha in vitro primes the respiratory burst,
      delays apoptosis and induces the expression of several genes including
      chemokines, and TNF-alpha itself. This study aimed to determine the impact of TNF
      alpha exposure on the expression of neutrophil genes and proteins that regulate
      apoptosis. Quantitative PCR and RNA-Seq, identified changes in expression of
      several apoptosis regulating genes in response to TNF-alpha exposure. Up
      regulated genes included TNF-alpha itself, and several anti-apoptotic genes,
      including BCL2A1, CFLAR (cFLIP) and TNFAIP3, whose mRNA levels increased above
      control values by between 4-20 fold (n = 3, P < 0.05). In contrast, the
      expression of pro-apoptotic genes, including CASP8, FADD and TNFRSF1A and
      TNFRSF1B, were significantly down-regulated following TNF-alpha treatment. These
      changes in mRNA levels were paralleled by decreases in protein levels of caspases
      8 and 10, TRADD, FADD, TNFRSF1A and TNFRSF1B, and increased cFLIP protein levels,
      as detected by western blotting. These data indicate that when neutrophils are
      triggered by TNF-alpha exposure, they undergo molecular changes in
      transcriptional expression to up-regulate expression of specific anti-apoptotic
      proteins and concomitantly decrease expression of specific proteins involved in
      death receptor signaling which will alter their function in TNF-alpha rich
      environments. 

PMID- 27042301
TI  - VTX-1463, a novel TLR-8 agonist, attenuates nasal congestion after ragweed
      challenge in sensitized beagle dogs.
AB  - VTX-1463 is a selective toll-like receptor (TLR) 8 agonist that activates a
      subset of innate immune cells to produce a unique cytokine profile. Delivery of
      VTX-1463 via nasal spray may modulate the nasal response in allergic rhinitis.
      The aim of this study was to determine the effects of VTX-1463 on the nasal
      response in a dog model of allergic rhinitis. Ragweed (RW)-sensitized dogs were
      pretreated with increasing doses of VTX-1463 1 day prior to RW challenge or with
      two doses (4 or 8 days and 1 day prior to RW). Changes in nasal cavity volume
      (NV) were determined by acoustic rhinometry and nasal lavage fluid was assessed
      for histamine, lipid mediators, and cellular infiltrates at sequential times
      following RW challenge. VTX-1463 pretreatment significantly preserved NV during
      the acute response to RW challenge for all doses tested. The area under the curve
      (AUC) for NV over the 1.5 h assessment period in RW challenged vehicle controls
      averaged 51.5% (SEM: +/-2.12%) of the baseline NV over all studies. A single 100
      ug dose of VTX-1463 given 1 day prior to RW yielded an AUC for NV of 69.3% (+/
      6.59%) of baseline, while a 1000 ug dose administered twice (8 days and 1 day
      prior to RW) resulted in an AUC for NV of 85.4% (+/-4.74%, P < 0.05) of baseline.
      For a single 1000 ug VTX-1463 dose 1 day prior to RW, multiple mediators produced
      by mast cells, including histamine, PGE2, PGD2, and cysteinyl LTs, were
      significantly reduced relative to the vehicle control. The selective TLR8
      agonist, VTX-1463, preserved NV in a dose-dependent manner in the acute phase of
      a nasal allergic response. The therapeutic effect appears to result from
      attenuated mast cell mediator release. Modulating the local cytokine response via
      TLR8 agonism appears to have a therapeutic effect on the acute allergic nasal
      response. 

PMID- 27042302
TI  - Prostaglandin D2 metabolites as a biomarker of in vivo mast cell activation in
      systemic mastocytosis and rheumatoid arthritis.
AB  - Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and
      allergic conditions. Less well understood is the role of MCs in non-allergic
      inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles
      for MCs in human diseases has been hampered by the lack of a well-accepted
      biomarker for monitoring in vivo MC activation. This study aimed to investigate
      the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC
      activation in patients with SM, and apply this biomarker to assess MC involvement
      in relation to RA disease activity. A prospective, cross-sectional cohort study
      was conducted to measure a major urinary metabolite of prostaglandin D2, T-PGDM.
      Urine samples were collected from patients with RA (n = 60), SM (n = 17) and
      healthy normal controls (n = 16) and T-PGDM excretion was determined by enzyme
      immunoassay as nanograms per milligram of urinary creatinine (ng/mg Cr). Mean
      urinary T-PGDM excretion was significantly higher (p < 0.01) in patients with SM
      compared to controls (37.2 vs. 11.5 ng/mg Cr) with 65% of SM patients showing
      elevated levels. One third of patients with RA had elevated T-PGDM excretion, and
      the mean level in the RA group (20.0 ng/mg Cr) was significantly higher than
      controls (p < 0.01). Medications inhibiting cyclooxygenase reduced T-PGDM
      excretion. Urinary T-PGDM excretion appears promising as a biomarker of in vivo
      MC activity and elevated levels in 33% of patients with RA provides evidence of
      MC activation in this disease. 

PMID- 27042303
TI  - IL-6 and IL-17A degradation by mast cells is mediated by a serglycin:serine
      protease axis.
AB  - Mast cells contain large amounts of fully active proteases that are stored in
      complex with serglycin proteoglycan in their secretory granules. Upon
      degranulation, such serglycin:protease complexes are released to the
      extracellular space and can potentially have an impact on the local inflammatory
      reaction, either through direct effects of serglycin proteoglycan or through
      effects mediated by its bound proteases. The objective of this study was to
      address this scenario by investigating the possibility that serglycin-associated
      proteases can regulate levels of pro-inflammatory cytokines. Indeed, we show here
      that activated cultured peritoneal mast cells from wild type mice efficiently
      reduced the levels of exogenously administered IL-6 and IL-17A, whereas serglycin
      deficient mast cells lacked this ability. Furthermore, our data suggest that the
      reduction of IL-6 and IL-17A concentrations is due to proteolytic degradation
      mediated by serglycin-dependent serine proteases. Moreover, we show that
      activated mast cells have the capacity to release IL-6 and that the levels of
      this cytokine in supernatants were markedly higher in cultures of serglycin
      deficient versus serglycin-sufficient mast cells, suggesting that serglycin
      dependent serine proteases also participate in the regulation of endogenously
      produced IL-6. In summary, although the general consensus is that mast cells have
      a pathogenic impact on inflammatory settings, this study identifies a role for a
      mast cell-derived serglycin:serine protease axis in down-regulating levels of
      major inflammatory cytokines. These findings support the notion that mast cells
      could have a dual role in inflammatory settings, by both being able to secrete
      pathogenic compounds and being able to regulate their levels after release. 

PMID- 27042304
TI  - Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity
      by inducing TGF-beta secretion from regulatory T cells.
AB  - CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to
      autoimmune and/or inflammatory diseases, and maintain host immune homeostasis.
      However, CD4(+)CD25(high)Foxp3(+) T cells reportedly contribute to disease
      progression by over suppressing immune responses in some chronic infections. In
      this study, kinetic and functional analyses of CD4(+)CD25(high)Foxp3(+) T cells
      were performed in cattle with bovine leukemia virus (BLV) infections, which have
      reported immunosuppressive characteristics. In initial experiments, production of
      the Th1 cytokines IFN-gamma and TNF-alpha was reduced in BLV-infected cattle
      compared with uninfected cattle, and numbers of IFN-gamma or TNF-alpha producing
      CD4(+) T cells decreased with disease progression. In contrast, IFN-gamma
      production by NK cells was inversely correlated with BLV proviral loads in
      infected cattle. Additionally, during persistent lymphocytosis disease stages, NK
      cytotoxicity was depressed as indicated by low expression of the cytolytic
      protein perforin. Concomitantly, total CD4(+)CD25(high)Foxp3(+) T cell numbers
      and percentages of TGF-beta(+) cells were increased, suggesting that TGF-beta
      plays a role in the functional declines of CD4(+) T cells and NK cells. In
      further experiments, recombinant bovine TGF-beta suppressed IFN-gamma and TNF
      alpha production by CD4(+) T cells and NK cytotoxicity in cultured cells. These
      data suggest that TGF-beta from CD4(+)CD25(high)Foxp3(+) T cells is
      immunosuppressive and contributes to disease progression and the development of
      opportunistic infections during BLV infection. 

PMID- 27042305
TI  - The influence of atopy and asthma on immune responses in inner-city adults.
AB  - Asthma in the inner-city population is usually atopic in nature, and is
      associated with significant morbidity and mortality. However, the underlying
      immune abnormalities that underlie asthma in urban adults have not been well
      defined. We investigated the influence of atopy and asthma on cytokine responses
      of inner-city adult women to define immune abnormalities associated with asthma
      and atopy. Blood samples were collected from 509 of 606 inner-city women enrolled
      in the Urban Environment and Childhood Asthma (URECA) study. We tested for
      associations between atopy and asthma status and cytokine responses in peripheral
      blood mononuclear cells incubated ex vivo with a panel of innate and adaptive
      immune stimulants. Atopic subjects had heightened Th2 cytokine responses (IL-4,
      IL-5, IL-13) to cockroach and dust mite antigens, tetanus toxoid, and
      phytohemagglutinin (P < 0.05 for all). Differences in cytokine responses were
      greatest in response to stimulation with cockroach and dust mite. In a
      multivariate analysis, atopy was broadly related to increased Th2-like responses
      to all antigens and PHA, while asthma was only weakly related to mitogen-induced
      IL-4 and IL-5 responses. There were few asthma or allergy-related differences in
      responses to innate stimuli, including IFN-alpha and IFN-gamma responses. In this
      inner-city adult female population, atopy is associated with enhanced Th2
      responses to allergens and other stimuli, and there was little or no additional
      signal attributable to asthma. In particular, these data indicate that altered
      systemic interferon and innate immune responses are not associated with allergies
      and/or asthma in inner-city women. 

PMID- 27042306
TI  - Acute hyperglycemia impairs IL-6 expression in humans.
AB  - Normal glucose metabolism is critical to immune function but the effects of short
      term hyperglycemia on immunity are not well described. To study this phenomenon,
      we induced hyperglycemia in healthy subjects for 2 h with intravenous dextrose
      and octreotide. An RNA-seq analysis of whole blood RNA demonstrated alterations
      in multiple immune pathways and transcripts during acute hyperglycemia including
      decreased transcription of IL-6, an important component of both innate and
      adaptive immune responses. Additional in vitro studies of human peripheral blood
      mononuclear cells (PBMCs) exposed to high glucose confirmed decreased IL-6
      expression, most prominently in CD14(+)CD16(+) intermediate monocytes.
      Hyperglycemia also reduced IL-17A expression suggesting further impairment of
      immune responses during acute hyperglycemia. These findings demonstrate multiple
      defective immune responses in acute hyperglycemia and suggest a novel role for
      intermediate monocytes as metabolically sensitive innate immune cells. 

PMID- 27042307
TI  - Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by
      stimulation with interferon gamma and Porphyromonas gingivalis
      lipopolysaccharide.
AB  - Periodontitis is a chronic inflammatory disorder caused by specific bacteria
      residing in the biofilm, particularly Porphyromonas gingivalis (Pg). Sprouty2
      (Spry2) functions as a negative regulator of the fibroblast growth factor (FGF)
      signaling pathway. We previously demonstrated that sequestration of Spry2 induced
      proliferation and osteogenesis in osteoblastic cells by basic FGF (bFGF) and
      epidermal growth factor (EGF) stimulation in vitro, but diminished cell
      proliferation in gingival epithelial cells. In addition, Spry2 knockdown in
      combination with bFGF and EGF stimulation increases periodontal ligament cell
      proliferation and migration accompanied by prevention of osteoblastic
      differentiation. In this study, we investigated the mechanisms through which
      Spry2 depletion by interferon (IFN) gamma and Pg lipopolysaccharide (LPS)
      stimulation affected the physiology of macrophages in vitro. Transfection of
      macrophages with Spry2 small-interfering RNA (siRNA) promoted the expression of
      genes characteristic of M2 alternative activated macrophages, induced interleukin
      (IL)-10 expression, and enhanced arginase activity, even in cells stimulated with
      IFNgamma and Pg LPS. In addition, we found that phosphoinositide 3-kinase (PI3K)
      and AKT activation by Spry2 downregulation enhanced efferocytosis of apoptotic
      cells by increasing Rac1 activation and decreasing nuclear factor kappa B
      (NFkappaB) p65 phosphorylation but not signal transducer and activator of
      transcription 1 (STAT1) phosphorylation. Collectively, our results suggested that
      topical administration of Spry2 inhibitors may efficiently resolve inflammation
      in periodontal disease as macrophage-based anti-inflammatory immunotherapy and
      may create a suitable environment for periodontal wound healing. These in vitro
      findings provide a molecular basis for new therapeutic approaches in periodontal
      tissue regeneration. 

PMID- 27042308
TI  - Magnetic resonance-guided high-intensity focused ultrasound combined with
      radiotherapy for palliation of head and neck cancer-a pilot study.
AB  - BACKGROUND: Radiotherapy is a critical component of the multidisciplinary
      management of cancers of the head and neck. It may comprise the primary curative
      treatment modality or is used in an adjuvant setting to improve local control and
      survival by preventing seeding and reseeding of distant metastases from
      persistent reservoirs of locoregional disease. Although considerable advances
      have been made recently in the fields of radiotherapy, systemic treatment and
      surgery for head and neck tumours, locoregional recurrence rates remain high and
      treatment side effects may have severe impact on patients' quality of life.
      Magnetic resonance-guided high-intensity focused ultrasound (MRg-HIFU) is a novel
      technique in the treatment of cancer that has the potential to improve tumour
      cure rates and decrease treatment-related toxicity. Clinical applications of HIFU
      are being used increasingly for the treatment of several tumour sites, for
      example uterine leiomyomas and prostate cancer. METHODS/DESIGN: The pilot study
      presented here is an initial step toward utilizing MRg-HIFU for head and neck
      cancer treatment. The rationale for novel treatment options in head and neck
      cancer is reviewed as well as emerging evidence that support the increasing
      clinical utilization of MRg-HIFU. DISCUSSION: This pilot study aims to assess
      safety, toxicity and feasibility of MRg-HIFU treatments to the head and neck
      region and to evaluate changes caused by MRg-HIFU within the treated tumour
      regions based on post-treatment MRI.

PMID- 27042309
TI  - Subcellular Behaviour Evaluation of Nanopharmaceuticals with Aggregation-Induced
      Emission Molecules.
AB  - Nanopharmaceuticals possess a myriad of advantages for disease treatment, not
      only in delivering therapeutic agents, but also in deciphering their innate
      intracellular or subcellular behaviours, providing detailed diagnostic and
      prognostic information, quantifying treatment efficacy and designing better
      therapeutics. To evaluate the subcellular behaviour of nanopharmaceuticals,
      colourful fluorescence is the most potential technique, because it is capable of
      painting the subcellular detail in three dimensions with high resolution.
      Furthermore, the fluorescence is switchable, and thus the subcellular details can
      be lightened specifically without the undesirable background. However, most
      nanopharmaceuticals lack a fluorescent report group, and its introduction
      requires extra steps. Moreover, the introduced fluorescent groups can suffer from
      concentration quenching or aggregation-caused quenching (ACQ) when they are
      embedded in nanopharmaceuticals at a high concentration. The unique aggregation
      induced emission (AIE) effect provides a straightforward solution. The aromatic
      cores of AIE molecules are always hydrophobic and do not undergo the ACQ effect
      even at high concentrations. Hence, AIE molecules can be directly introduced as
      building blocks to provide the driving force for the self-assembly of
      nanopharmaceuticals and can allow us to develop label-free, ACQ-free and
      luminescent nanopharmaceuticals that can simultaneously implement drug delivery
      and subcellular behaviour evaluation. This review presents different types of AIE
      molecules-based nanopharmaceuticals and their biological properties and
      applications for imaging subcellular behaviours, including the drug releasing
      process, metabolism of nanopharmaceuticals, subcellular distributions of drug and
      carriers, and therapeutic effect. With detailed acquaintance of these subcellular
      behaviours, we anticipate that the research we discuss in this review can inspire
      other scientists to develop next generation nanopharmaceuticals that can be
      guided by fluorescence imaging and thus can realize concisely controllable drug
      delivery.

PMID- 27042310
TI  - Exploring the environmental drivers of waterfowl movement in arid landscapes
      using first-passage time analysis.
AB  - BACKGROUND: The movement patterns of many southern African waterfowl are typified
      by nomadism, which is thought to be a response to unpredictable changes in
      resource distributions. Nomadism and the related movement choices that waterfowl
      make in arid environments are, however, poorly understood. Tracking multiple
      individuals across wide spatiotemporal gradients offers one approach to
      elucidating the cues and mechanisms underpinning movement decisions. We used
      first-passage time (FPT) to analyse high spatial and temporal resolution
      telemetry data for Red-billed Teal and Egyptian Geese across a 1500 km
      geographical gradient between 2008 and 2014. We tested the importance of several
      environmental variables in structuring movement patterns, focusing on two
      competing hypotheses: (1) whether movements are driven by resource conditions
      during the current period of habitat occupation (reactive movement hypothesis),
      or (2) whether movements are structured by shifts in the magnitude and direction
      of environmental variables at locations prior to occupation (prescient movement
      hypothesis). RESULTS: An increase in rainfall at a 32 day lag (i.e., prior to
      wetland occupancy), along with tagging site, were significant predictors of FPT
      in both waterfowl species. There was a positive relationship between NDVI and FPT
      for Egyptian Geese during this 32 day period; the relationship was negative for
      Red-billed Teal. Consistent with findings for migratory grazing geese, Egyptian
      Geese prioritised food quality over food biomass. Red-billed Teal showed few
      immediate responses to wetland filling, contrary to what one would predict for a
      dabbling duck, suggesting high dietary flexibility. Our results were consistent
      with the prescient movement hypothesis. CONCLUSIONS: Using FPT analysis we showed
      that the proximate drivers of southern African waterfowl movement are the
      dynamics of rainfall and primary productivity. Waterfowl appeared to be able to
      perceive and respond to temporal shifts in resource conditions prior to habitat
      patch occupation. This in turn suggests that their movements in semi-arid
      landscapes may be underpinned by intimate knowledge of the local environment;
      waterfowl pursue a complex behavioural strategy, locating suitable habitat
      patches proactively, rather than acting as passive respondents.

PMID- 27042311
TI  - Prognostic value of the recovery time of continuous normal voltage in amplitude
      integrated electroencephalography in out-of-hospital cardiac arrest patients
      treated with therapeutic hypothermia: a retrospective study.
AB  - BACKGROUND: The early prediction of neurological outcomes in postcardiac arrest
      patients treated with therapeutic hypothermia (TH) remains challenging. Amplitude
      integrated electroencephalography (aEEG) is a type of quantitative EEG. A
      particular cutoff time from the return of spontaneous circulation (ROSC) to the
      recovery of a normal aEEG trace for predicting a good neurological outcome has
      not yet been established. The purpose of the present study was to examine the
      relation between neurological outcomes and the continuous normal voltage (CNV)
      recovery time in adult comatose survivors of cardiac arrest treated with TH and
      identify the recovery time cutoff for predicting a good neurological outcome.
      METHODS: We retrospectively evaluated adult survivors of cardiac arrest with
      initial shockable rhythm treated with TH and monitored with aEEG. A good outcome
      was defined as a cerebral performance category (CPC) of 1 or 2 at hospital
      discharge. A CNV trace was considered as the normal aEEG trace, and the CNV
      recovery time was defined as the time from ROSC to the initial CNV trace.
      RESULTS: The study included 30 patients, and of these patients, 22 had recovery
      of CNV trace. The median CNV recovery time was shorter among patients with a good
      outcome than that among those with a poor outcome (10.7 h [interquartile range
      (IQR), 7.4-15.8 h] vs. 28.6 h [IQR, 26.9-29.3 h]; p = 0.003). The area under the
      receiver operating characteristic curve of the CNV recovery time for predicting a
      good neurological outcome was 0.95 (95 % CI 0.86-1; p = 0.003), and the optimal
      cutoff was 23 h. The recovery of CNV trace within 23 h had a sensitivity of 89 %,
      specificity of 100 %, positive predictive value of 100 %, and negative predictive
      value of 86 % for predicting a good neurological outcome in all the patients,
      including the eight patients without recovery of CNV trace. CONCLUSIONS: A CNV
      recovery time cutoff of 23 h might help predict a good neurological outcome in
      adult survivors of cardiac arrest treated with TH.

PMID- 27042312
TI  - Maximal strength training as physical rehabilitation for patients with substance
      use disorder; a randomized controlled trial.
AB  - BACKGROUND: Patients with substance use disorder (SUD) suffer from multiple
      health and psychosocial problems. Because poor physical capacities following an
      inactive lifestyle may indeed contribute to these problems, physical training is
      often suggested as an attractive supplement to conventional SUD treatment.
      Strength training is shown to increase muscle strength and effectively improve
      health and longevity. Therefore we investigated the feasibility and effect of a
      maximal strength training intervention for SUD patients in clinical treatment.
      METHODS: 16 males and 8 females were randomized into a training group (TG) and a
      control group (CG). The TG performed lower extremities maximal strength training
      (85-90 % of 1 repetition maximum (1RM)) 3 times a week for 8 weeks, while the CG
      participated in conventional clinical activities. RESULTS: The TG increased hack
      squat 1RM (88 +/- 54 %), plantar flexion 1RM (26 +/- 20 %), hack squat rate of
      force development (82 +/- 29 %) and peak force (11 +/- 5 %). Additionally, the TG
      improved neural function, expressed as voluntary V-wave (88 +/- 83 %). The CG
      displayed no change in any physical parameters. The TG also reduced anxiety and
      insomnia, while the CG reduced anxiety. CONCLUSION: Maximal strength training was
      feasible for SUD patients in treatment, and improved multiple risk factors for
      falls, fractures and lifestyle related diseases. As conventional treatment
      appears to have no effect on muscle strength, systematic strength training should
      be implemented as part of clinical practice. TRIAL REGESTRATION:
      ClinicalTrials.gov Identifier: NCT02218970 (August 14, 2014).

PMID- 27042313
TI  - 'Struggling to be a defender of health' -a qualitative study on the pharmacists'
      perceptions of their role in antibiotic consumption and antibiotic resistance in
      Romania.
AB  - BACKGROUND: Antibiotic resistance is a serious global public health problem
      directly correlated to high antibiotic consumption. Romania is one of the
      European countries with the highest rates of antibiotic consumption, non
      prescription antibiotics use and resistance of several pathogens to antibiotics.
      Pharmacists are an important stakeholder in respect to antibiotic management and
      context specific research on this topic is needed. The aim of the research is to
      increase the understanding of how community pharmacists in Romania perceive their
      roles in respect to antibiotic consumption and antibiotic resistance. Semi
      structured interviews with 18 pharmacists were conducted to explore the
      perceptions and attitudes of pharmacists towards their roles on antibiotics
      consumption and antibiotic resistance. Manifest and latent qualitative content
      analysis was used to analyse interview transcripts. RESULTS: Three sub-themes
      emerged from the analysis. 'Maintaining equilibrium between ethics, law and
      economy' expresses how pharmacists often feel when trying to fulfil their duties
      considering all the dimensions of the pharmacist profession.' Antibiotic
      resistance problem rooted in a low social capital environment' reflects the
      pharmacists' perceptions of the deep causes of antibiotic resistance and the
      underlying problems that perpetuate the status quo and impact their role in
      relation to this problem. Wanting to fulfil their educational role illustrates
      how the pharmacists feel they could best contribute to improving the present
      situation. The overarching theme 'Undervalued medicines' professionals struggling
      with agency related and structural barriers to meet their deontological duties'-
      meaning the ethical responsibilities that come with the pharmacy practice,
      reflects that the pharmacists see their roles as being challenged by several
      barriers. CONCLUSIONS: A health system and societal context perspective is
      helpful in order to understand the pharmacists' roles in respect to antibiotic
      consumption and antibiotic resistance. Health promotion interventions and policy
      revisions should take into account concepts of structure and agency. These could
      highlight barriers that pharmacists encounter in their activities related to
      antibiotics management.

PMID- 27042314
TI  - HIV/AIDS related commodities supply chain management in public health facilities
      of Addis Ababa, Ethiopia: a cross-sectional survey.
AB  - BACKGROUND: A wide range of pharmaceutical products are needed for diagnosis,
      treatment, and prevention of HIV/AIDS. However, interrupted supplies and stock
      outs are the major challenges in the supply chain of ARV medicines and related
      commodities. The aim of this study was to assess the supply chain management of
      HIV/AIDS related commodities in public health facilities of Addis Ababa,
      Ethiopia. METHODS: A descriptive cross-sectional survey complemented by
      qualitative method was conducted in 24 public health facilities (4 hospitals and
      20 health centers). A semi-structured questionnaire and observation check list
      were used to collect data on HIV/AIDS related service, reporting and ordering;
      receiving, transportation and storage condition of ARV medicines and test kits;
      and supportive supervision and logistics management information system. In
      addition, in-depth interview with flexible probing techniques was used to
      complement the quantitative data with emphasis to the storage condition of ARV
      medicines and test kits. Quantitative data was analyzed using SPSS version-20.
      Analysis of qualitative data involved rigorous reading of transcripts in order to
      identify key themes and data was analyzed using thematic approach. RESULTS: The
      study revealed that 16 health centers and one hospital had recorded and reported
      patient medication record. Six months prior to the study, 14 health centers and 2
      hospitals had stopped VCT services for one time or more. Three hospitals and 18
      health centers claimed to have been able to submit the requisition and report
      concerning ARV medicines to Pharmaceutical Fund and Supply Agency according to
      the specific reporting period. More than three-fourth of the health centers had
      one or more emergency order of ARV medicines on the day of visit, while all of
      hospitals had emergency order more than 3 times within 6 months prior to the
      study. All of the hospitals and nearly half of the health centers had an
      emergency order of test kits more than 3 times in the past 6 months. Overall,
      nearly 3/4th of the health facilities faced stock-out of one or more ARV
      medicines and test kits on the day of visit. CONCLUSION: There was no adequate
      data on patient medication record and stock status of HIV/AIDS related
      commodities. Moreover there were frequent stock-outs of ARV medicines and HIV
      test kits, which was an indicator of the weak supply chain management. Hospitals
      and health centers, therefore, should devise a system to capture and make use of
      patient medication record and stock status information so as to ensure continuous
      supply of the commodities.

PMID- 27042315
TI  - Endovascular management of renal artery aneurysms using the multilayer flow
      modulator.
AB  - OBJECTIVE: Our aim was to describe our experience of the Multilayer Flow
      Modulator (MFM, Cardiatis, Isnes, Belgium) used in the treatment of type III
      renal artery aneurysms (RAA). METHODS: This is a single-centre study. 3 patients
      (2 men and 1 woman; mean age 59 years; range 41-77 years) underwent treatment of
      a type III renal artery aneurysm using the MFM. The indications were a 23.9 mm
      type III RAA at the bifurcation of the upper and lower pole vessels, with 4 side
      branches; a 42.4 mm type III saccular RAA at the renal hilum; and a 23 mm type
      III RAA at the origin of the artery, supplying the upper pole. RESULTS: Patients
      had a mean follow-up of 27 months, and were assessed by perioperative renal
      function tests, and repeat postoperative CT scan. There were no immediate
      postoperative complications or mortality. The first patient's aneurysm shrank by
      8.6 mm, from 23.9 to 15.3 mm over 19 months, with all 4 side branches remaining
      patent. The largest aneurysm at 42.4 mm completely thrombosed, while the renal
      artery remained patent to the kidney. The final patient refused to have any
      follow-up scans but had no deterioration in renal function below 30 mL/min, and
      no further symptoms reported. CONCLUSIONS: The MFM is safe and effective in the
      management of patients with complex renal artery aneurysms. The MFM can be used
      to treat branched or distal renal artery aneurysms with exclusion of the aneurysm
      from the circulation, while successfully preserving the flow to the side branches
      and kidney. Initial results are promising, however, longer follow-up and a larger
      cohort are required to prove the effectiveness of this emerging technology.

PMID- 27042316
TI  - Estimated incidence and risk factors of sudden unexpected death.
AB  - OBJECTIVE: In this manuscript, we estimate the incidence and identify risk
      factors for sudden unexpected death in a socioeconomically and racially diverse
      population in one county in North Carolina. Estimates of the incidence and risk
      factors contributing to sudden death vary widely. The Sudden Unexpected Death in
      North Carolina (SUDDEN) project is a population-based investigation of the
      incidence and potential causes of sudden death. METHODS: From 3 March 2013 to 2
      March 2014, all out-of-hospital deaths in Wake County, North Carolina, were
      screened to identify presumed sudden unexpected death among free-living residents
      between the ages of 18 and 64 years. Death certificate, public and medical
      records were reviewed and adjudicated to confirm sudden unexpected death cases.
      RESULTS: Following adjudication, 190 sudden unexpected deaths including 122 men
      and 68 women were identified. Estimated incidence was 32.1 per 100 000 person
      years overall: 42.7 among men and 22.4 among women. The majority of victims were
      white, unmarried men over age 55 years, with unwitnessed deaths at home.
      Hypertension and dyslipidaemia were common in men and women. African-American
      women dying from sudden unexpected death were over-represented. Women who were
      under age 55 years with coronary disease accounted for over half of female
      participants with coronary artery disease. CONCLUSIONS: The overall estimated
      incidence of sudden unexpected death may account for approximately 10% of all
      deaths classified as 'natural'. Women have a lower estimated incidence of sudden
      unexpected death than men. However, we found no major differences in age or
      comorbidities between men and women. African-Americans and young women with
      coronary disease are at risk for sudden unexpected death.

PMID- 27042317
TI  - Nutritional strategies for skeletal and cardiovascular health: hard bones, soft
      arteries, rather than vice versa.
AB  - The focus of this paper is to explore better strategies for optimising bone
      strength and reducing risk of fracture, while at the same time decreasing risk of
      cardiovascular disease. The majority of Americans do not consume the current
      recommended dietary allowance for calcium, and the lifetime risk of osteoporosis
      is about 50%. However, traditional mononutrient calcium supplements may not be
      ideal. We comprehensively and systematically reviewed the scientific literature
      in order to determine the optimal dietary strategies and nutritional supplements
      for long-term skeletal health and cardiovascular health. To summarise, the
      following steps may be helpful for building strong bones while maintaining soft
      and supple arteries: (1) calcium is best obtained from dietary sources rather
      than supplements; (2) ensure that adequate animal protein intake is coupled with
      calcium intake of 1000 mg/day; (3) maintain vitamin D levels in the normal range;
      (4) increase intake of fruits and vegetables to alkalinise the system and promote
      bone health; (5) concomitantly increase potassium consumption while reducing
      sodium intake; (6) consider increasing the intake of foods rich in vitamins K1
      and K2; (7) consider including bones in the diet; they are a rich source of
      calcium-hydroxyapatite and many other nutrients needed for building bone. 

PMID- 27042318
TI  - Long-term survival after surgical aortic valve replacement among patients over 65
      years of age.
AB  - OBJECTIVE: Surgical aortic valve replacement (AVR) remains the gold standard
      therapy for severe aortic stenosis. Long-term survival data following AVR is
      required. Our objective was to provide a detailed contemporary benchmark of long
      term survival following AVR among elderly patients (>=65 years) in the UK.
      METHODS: We conducted a retrospective cohort study of 1815 adult patients
      undergoing surgical AVR+/- coronary artery bypass graft (CABG) surgery at a
      single UK centre between 1996 and 2011. Our main outcome was patient survival,
      which was assessed by linkage to census records at the Office for National
      Statistics. RESULTS: The mean age of the cohort was 75 (+/-5.6) years. Patients
      in the AVR alone group had a slightly higher median survival of 10.9 (95% CI 10.5
      to 11.8) years than the AVR+CABG group which had a median survival of 9.6 (95% CI
      8.7 to 10.1) years (p=0.001 of log-rank test (LRT) for equality of survivor
      functions). The presence of chronic kidney disease, severely impaired left
      ventricular function or being a current smoker were each associated with a >=50%
      increased risk of long-term mortality. Comparison of our study cohort patients
      and the reference (operation year, age and gender matched) UK population
      suggested no difference in survival probability up to 8 years (p=0.55). However,
      for longer periods of follow-up, the difference became increasingly significant
      (p<0.0001). CONCLUSIONS: Long-term survival following surgical AVR in patients
      over 65 years of age is excellent and up to 8 years is comparable to the matched
      general population.

PMID- 27042319
TI  - Pathophysiological effects of different risk factors for heart failure.
AB  - BACKGROUND: Hypertension and type 2 diabetes mellitus (T2DM) are important causes
      of non-ischaemic heart failure (HF). Understanding the pathophysiology of early
      HF may guide screening. We hypothesised that the underlying physiology differed
      according to aetiology. METHODS: In this cross-sectional study of 521
      asymptomatic community-based subjects >=65 years with >=1 HF risk factors, 187
      participants (36%) had T2DM and hypertension (T2DM+/HTN+), 109 (21%) had T2DM
      with no hypertension (T2DM+/HTN-) and 72 (14%) had neither T2DM nor hypertension
      (T2DM-/HTN-). In 153 patients (29%), clinic blood pressure was >=140/90 mm Hg,
      defined as active hypertension (T2DM-/HTN+). All underwent a comprehensive
      echocardiogram, including conventional parameters for systolic and diastolic
      function as well as global longitudinal strain (GLS), diastolic strain (DS) and
      DS rate (DSR). A 6 min walk (6MW) test was used to assess functional capacity.
      RESULTS: GLS in T2DM-/HTN+ group (-18.9+/-2.7%) was similar to that in T2DM-/HTN-
      group (-19.4+/-2.4%) and greater than T2DM+/HTN- (-18.0+/-2.8%, p=0.005). DS in
      T2DM-/HTN- (0.47+/-0.15%) exceeded that in T2DM-/HTN+ (0.43+/-0.14%) and
      T2DM+/HTN- (0.43+/-0.13%). 6MW distance was preserved in T2DM-/HTN+ (482+/-85 m)
      and reduced in T2DM+/HTN- (469+/-93, p<0.001). Those with T2DM and active
      hypertension had worst GLS, DS, DSR and shortest 6MW distance (p<0.002). In
      multivariable analysis, GLS was associated with T2DM but neither active
      hypertension nor a history of hypertension. Diastolic markers and left
      ventricular (LV) mass were associated with hypertension and T2DM. Thus, patients
      with HF risk factors show different functional disturbances according to
      aetiology. CONCLUSIONS: Patients with hypertension had relatively less impaired
      GLS and preserved 6MW distance but more impaired diastolic function.

PMID- 27042320
TI  - Effects of paediatric HIV infection on electrical conduction of the heart.
AB  - OBJECTIVE: To investigate the effects of HIV infection in children on heart
      electrical conduction, particularly to delineate the effects of HIV infection
      from treatment. METHODS: On a 12-lead ECG, available for 37 antiretroviral
      therapy (ART) naive, 42 ART-exposed vertically-acquired HIV-infected and 50
      healthy children in Jakarta, Indonesia, we measured cardiac conduction
      parameters: PR, QRS, and QTc (corrected using Bazett's formula) intervals. The
      associations between HIV infection/treatment status and ECG intervals were
      evaluated using general linear modelling with further adjustment for potential
      confounders or intermediary variables. Findings are presented as (adjusted) mean
      differences between each of the two HIV groups and healthy children. RESULTS:
      Although not exceeding the clinical threshold for long QT (QTc >460 ms for girls
      and >440 ms for boys) compared to healthy children, mean QTc intervals were
      longer in ART-naive (difference 18.2 ms, 95% CI 7.0 to 29.3) and, to greater
      extent, in ART-exposed HIV-infected children (difference 28.9 ms, 19.3 to 38.5).
      Following adjustment for RR interval, age and height, prolongation of PR interval
      was seen only in ART-naive HIV-infected children (difference 12.9 ms, 2.4 to
      23.3). Cardiac mass/function, high-sensitive C reactive protein, cholesterol and
      glycated haemoglobin levels, systolic and diastolic blood pressures, or postnatal
      parental smoking exposure did not affect these associations. No difference in the
      QRS interval was observed between groups. CONCLUSIONS: Prolongation of the QTc
      interval occurs in ART-naive HIV-infected children and, to a greater extent, in
      the ART-exposed children, whereas a longer PR interval appears to be seen only
      among ART-naive HIV-infected children.

PMID- 27042321
TI  - Distribution of lifespan gain from primary prevention intervention.
AB  - OBJECTIVE: When advising patients about possible initiation of primary prevention
      treatment, clinicians currently do not have information on expected impact on
      lifespan, nor how much this increment differs between individuals. METHODS:
      First, UK cardiovascular and non-cardiovascular mortality data were used to
      calculate the mean lifespan gain from an intervention (such as a statin) that
      reduces cardiovascular mortality by 30%. Second, a new method was developed to
      calculate the probability distribution of lifespan gain. Third, we performed a
      survey in three UK cities on 11 days between May-June 2014 involving 396
      participants (mean age 40 years, 55% male) to assess how individuals evaluate
      potential benefit from primary prevention therapies. RESULTS: Among numerous
      identical patients, the lifespan gain, from an intervention that reduces
      cardiovascular mortality by 30%, is concentrated within an unpredictable
      minority. For example, men aged 50 years with national average cardiovascular
      risk have mean lifespan gain of 7 months. However, 93% of these identical
      individuals gain no lifespan, while the remaining 7% gain a mean of 99 months.
      Many survey respondents preferred a chance of large lifespan gain to the
      equivalent life expectancy gain given as certainty. Indeed, 33% preferred a 2%
      probability of 10 years to fivefold more gain, expressed as certainty of 1 year.
      CONCLUSIONS: People who gain lifespan from preventative therapy gain far more
      than the average for their risk stratum, even if perfectly defined. This may be
      important in patient decision-making. Looking beyond mortality reduction alone
      from preventative therapy, the benefits are likely to be even larger.

PMID- 27042322
TI  - Maternal ethnicity and its impact on the haemodynamic and blood pressure response
      to labetalol for the treatment of antenatal hypertension.
AB  - OBJECTIVE: Blood pressure (BP) control outside pregnancy is associated with a
      reduction in adverse cardiovascular events, and in pregnancy with improved
      outcomes. Outside pregnancy, there is evidence beta-blockers are less effective
      in controlling BP in black populations. However, in pregnancy, labetalol is
      recommended as a universal first-line treatment, without evidence for the impact
      of ethnicity on its efficacy. We sought to compare haemodynamic responses to
      labetalol in black and white pregnant patients. METHODS: This was a prospective
      observational cohort study in a London teaching hospital. Maternal haemodynamics
      were assessed in 120 pregnant women treated with labetalol monotherapy.
      Measurements were taken at presentation, 1 and 24 h after treatment. Participants
      were monitored regularly until delivery. Statistical analysis was performed by
      multilevel modelling. RESULTS: Both groups exhibited similar temporal trends in
      haemodynamic changes over the first 24 h following labetalol. Both showed a
      reduction in BP and peripheral vascular resistance within 1 h and in heart rate
      after 24 h. There was no change in cardiac output and stroke volume in either
      group. BP control (<140/90) was achieved at 1 h in 79.7% of the white and 77% of
      the black cohort. At 24 h, control was achieved among 83.1% and 63.9%, and up to
      the immediate intrapartum period control was achieved in 89.8% and 70.4% of white
      and black patients, respectively. CONCLUSIONS: There is no difference in the
      acute haemodynamic changes and hypertension can be controlled throughout
      pregnancy with labetalol monotherapy in excess of 70% pregnant black and white
      patients.

PMID- 27042323
TI  - Excess short-term mortality in women after isolated coronary artery bypass graft
      surgery.
AB  - OBJECTIVE: Female sex is considered a risk factor for adverse outcomes following
      isolated coronary artery bypass graft (CABG) surgery. We assessed the association
      between sex and short-term mortality following isolated CABG, and estimated the
      'excess' deaths occurring in women. METHODS: Short-term mortality was
      investigated in 13 327 consecutive isolated CABG patients in North Texas between
      January 2008 and December 2012. The association between sex and CABG short-term
      mortality, and the excess deaths among women were assessed via a propensity
      adjusted (by Society of Thoracic Surgeons-recognised risk factors) generalised
      estimating equations model approach. RESULTS: Short-term mortality was
      significantly higher in women than men (adjusted OR=1.39; 95% CI 1.04 to 1.86;
      p=0.027). This significantly greater risk translates into 35 'excess' deaths
      among women included in this study (>10% of the total 343 deaths in the study
      cohort) and into 392 'excess' deaths among the ~40 000 women undergoing isolated
      CABG in the USA each year. CONCLUSIONS: The higher risk associated with female
      sex lead to 35 'excess' deaths in women in this study cohort (over 10% of the
      total deaths) and to 392 'excess' deaths among women undergoing isolated CABG in
      the USA each year. Further research is needed to assess the causal mechanisms
      underlying this sex-related difference. Results of such work could inform the
      development and implementation of sex-specific treatment and management
      strategies to reduce women's mortality following CABG. Based on our results, if
      such work brought women's short-term mortality into line with men's, total short
      term mortality could be reduced by up to 10%.

PMID- 27042324
TI  - Is there a role for a local inpatient CT coronary angiography service in selected
      patients with acute coronary syndrome? A cohort analysis of inpatient tertiary
      centre referrals for invasive coronary angiography.
AB  - OBJECTIVE: To conduct a retrospective analysis of inpatients referred for
      invasive coronary angiography (ICA) at a tertiary centre, with suspected or
      confirmed acute coronary syndrome (ACS). METHODS: A retrospective cohort study
      was conducted at Jersey General Hospital. We evaluated 198 inpatients referred
      for ICA with suspected or confirmed ACS over a 3-year period. Patients presenting
      with ST elevation myocardial infarction were excluded. The primary outcome was to
      identify the number of patients who did not require subsequent coronary
      intervention following ICA. Patient variables were measured to establish those
      who met European Society of Cardiology (ESC) criteria for consideration of CT
      coronary angiography (CTCA) as an alternative to ICA. Cost of care for those
      referred for ICA was calculated. RESULTS: ICA demonstrated evidence of coronary
      heart disease requiring coronary intervention in 119 (60%) of the referred
      patients. 28 (35%) of the patients not requiring coronary intervention at ICA met
      ESC criteria for preassessment with CTCA. The cost of care for this subgroup was
      L9089 per patient. Inpatient CTCA was calculated at L376 per patient.
      CONCLUSIONS: Low-intermediate risk patients presenting with suspected or
      confirmed ACS to hospitals without onsite coronary revascularisation should be
      considered for in-hospital CTCA before consideration of ICA. Using CTCA as a
      gatekeeper for targeted ICA appears cost-effective, particularly for hospitals
      without the required onsite facilities.

PMID- 27042325
TI  - Examining uncertainty in the primary prevention of cardiovascular disease.

PMID- 27042326
TI  - Reproducibility of carotid-femoral pulse wave velocity in end-stage renal disease
      patients: methodological considerations.
AB  - BACKGROUND: In end-stage renal disease (ESRD) patients, increased arterial
      stiffness detected by carotid-femoral pulse wave velocity (cf-PWV) is associated
      with fatal cardiovascular events and all-cause mortality. Since cf-PWV is an
      operator-dependent technique, poor reproducibility may be a source of bias in the
      estimation of arterial stiffness. OBJECTIVES: We assessed the week-to-week
      reproducibility of cf-PWV and radial artery pulse wave analysis in healthy
      subjects and ESRD patients. We also determined the extent of patient eligibility,
      enrollment, acceptance, and comfort. METHODS: In a cohort study design,
      independent tonometric examinations of carotid, femoral, and radial arteries were
      conducted in 20 healthy subjects and 15 ESRD patients attending chronic
      hemodialysis treatments according to a randomized sequence by two operators on 2
      days scheduled 1-week apart. cf-PWV, augmentation index (AIx@HR75) and central
      pulse pressure (CPP) were the outcome measures. Patients were tested at mid-week
      and prior to dialysis treatment. The variability on the distance measured between
      the suprasternal notch and femoral site using two different methods (standard vs
      direct) was compared. A post-examination survey assessed acceptance and comfort
      associated with examinations. Reproducibility was evaluated by intra-class
      correlations (ICCs). RESULTS: The mean age for healthy subjects and ESRD patients
      was 45 +/- 12 and 63 +/- 16 years, respectively. ESRD patients had higher cf-PWV
      (p = 0.0002), elevated AIx@HR75 (p = 0.003), and increased CPP (p = 0.001)
      compared to healthy subjects. The mean inter-visit differences for all stiffness
      indices were non-significant (p > 0.05), but the mean inter-operator differences
      for the cf-PWV were significant only in the healthy subject group (-0.7 m/s; p =
      0.02). The ICCs between operators and visits were higher for the ESRD group
      compared to the healthy subjects (between operators, 0.870 vs 0.461; between
      visits, 0.830 vs 0.570). Distances were longer (p < 0.001), but less variable
      with the standard method compared to the direct method (healthy subjects, p =
      0.036; ESRD, p = 0.39). There was a high rate of patient acceptance and minimal
      discomfort. CONCLUSIONS: Week-to-week measurements of cf-PWV and pulse wave
      analysis are highly reproducible in ESRD patients prior to hemodialysis
      treatment. The high reproducibility and minimal test-to-test variations encourage
      use of cf-PWV to monitor changes in arterial stiffness and the efficacy of
      interventions in ESRD patients. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02196610.

PMID- 27042327
TI  - Exertional heat stroke in a young military trainee: is it preventable?
AB  - BACKGROUND: Heat stroke is a life-threatening condition with exertional heat
      stroke occurring frequently among soldiers and athletes. Because of its common
      occurrence, many military trainees practice preventive measures prior to any
      activity requiring severe exertion. Although it is said to be common in practice,
      different presentations of heat stroke are scarcely described in literature. CASE
      PRESENTATION: We describe a case of an exertional heat stroke in a 23-year-old
      male Sinhalese soldier who developed early changes of renal failure, liver
      failure and rhabdomyolysis. The patient initially presented with convulsions,
      delirium and loss of consciousness to an outside health care facility before
      being transferred to our institution. CONCLUSION: It is clear that heat stroke
      does occur in military trainees while preventive strategies are being practiced.
      It is important for those who provide healthcare to soldiers to provide proper
      advice on how to identify impending heat stroke prior to any exercises resulting
      in severe physical exertion. Further, treating physicians should educate all
      military trainees about preventive strategies.

PMID- 27042328
TI  - Changing paradigms in lower extremity reconstruction in war-related injuries.
AB  - BACKGROUND: Ballistic high-energy trauma has substantially increased the severity
      of non-fatal extremity injuries incurred in modern warfare. Expedient medical
      care, refinement in surgical techniques, and soft tissue coverage have brought
      about a paradigm shift in the management of lower extremity wounds during the
      last decade with an increased emphasis on limb salvage. METHODS: A literature
      based study was conducted to analyze reconstructive modalities based on the
      location, depth, and severity of wounds, as well as mechanism of injury,
      concomitant vascular injuries and open fractures, choice of flap, timing of
      definitive reconstruction, and complications. RESULTS: Extremity injuries account
      for over 60 % of injuries in the recent conflicts in Iraq and Afghanistan, with
      the majority secondary to explosive devices. The severity of these injuries is
      profound compared with civilian registries, and conventional injury scoring
      systems have failed to accurately predict outcomes in combat trauma. The mainstay
      of treatment is serial debridement, negative pressure therapy, fracture
      stabilization, and treatment of concomitant injuries by the forward medical teams
      with subsequent definitive reconstruction after transport to an advanced military
      treatment facility. Autologous reconstruction with free tissue transfer and
      pedicled flaps remains the primary modality for soft tissue coverage in limb
      salvage. Adjunct innovative modalities, such as external tissue expansion, dermal
      substitutes, and regenerative matrices, have also been successfully utilized for
      limb salvage. CONCLUSION: Lower extremity injuries account for the vast majority
      of injuries in modern warzones. Explosive devices represent the most common
      mechanism of injury, with blast impact leading to extensive soft tissue injuries
      necessitating complex reconstructive strategies. Serial debridement, negative
      pressure therapy, and autologous reconstruction with free tissue transfer and
      pedicled flaps remain the mainstay of treatment in recent conflicts.

PMID- 27042329
TI  - Open abdomen in trauma patients: a double-edged sword.
AB  - The use of open abdomen (OA) as a technique in the treatment of exsanguinating
      trauma patients was first described in the mid-19(th) century. Since the 1980s,
      OA has become a relatively new and increasingly common strategy to manage massive
      trauma and abdominal catastrophes. OA has been proven to help reduce the
      mortality of trauma. Nevertheless, the OA method may be associated with terrible
      and devastating complications such as enteroatmospheric fistula (EAF). As a
      result, OA should not be overused, and attention should be given to critical care
      as well as special management. The temporary abdominal closure (TAC) technique
      after abbreviated laparotomy was used to improve wound healing and facilitate
      final fascial closure of OA. Negative pressure therapy (NPT) is the most commonly
      used TAC method. 

PMID- 27042330
TI  - Genetic characterisation of PPARG, CEBPA and RXRA, and their influence on meat
      quality traits in cattle.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARG),
      CCAAT/enhancer binding protein alpha (CEBPA) and retinoid X receptor alpha (RXRA)
      are nuclear transcription factors that play important roles in regulation of
      adipogenesis and fat deposition. The objectives of this study were to
      characterise the variability of these three candidate genes in a mixed sample
      panel composed of several cattle breeds with different meat quality, validate
      single nucleotide polymorphisms (SNPs) in a local crossbred population (Angus -
      Hereford - Limousin) and evaluate their effects on meat quality traits (backfat
      thickness, intramuscular fat content and fatty acid composition), supporting the
      association tests with bioinformatic predictive studies. RESULTS: Globally, nine
      SNPs were detected in the PPARG and CEBPA genes within our mixed panel, including
      a novel SNP in the latter. Three of these nine, along with seven other SNPs
      selected from the Single Nucleotide Polymorphism database (SNPdb), including SNPs
      in the RXRA gene, were validated in the crossbred population (N = 260). After
      validation, five of these SNPs were evaluated for genotype effects on fatty acid
      content and composition. Significant effects were observed on backfat thickness
      and different fatty acid contents (P < 0.05). Some of these SNPs caused slight
      differences in mRNA structure stability and/or putative binding sites for
      proteins. CONCLUSIONS: PPARG and CEBPA showed low to moderate variability in our
      sample panel. Variations in these genes, along with RXRA, may explain part of the
      genetic variation in fat content and composition. Our results may contribute to
      knowledge about genetic variation in meat quality traits in cattle and should be
      evaluated in larger independent populations.

PMID- 27042331
TI  - Development of Stabilized Growth Factor-Loaded Hyaluronate- Collagen Dressing
      (HCD) matrix for impaired wound healing.
AB  - BACKGROUND: Diabetes mellitus is a disease lack of insulin, which has severely
      delayed and impaired wound healing capacity. In the previous studies, various
      types of scaffolds and growth factors were used in impaired wound healing.
      However, there were several limitations to use them such as short half-life of
      growth factors in vivo and inadequate experimental conditions of wound-dressing
      material. Thus, our study aimed to determine the biocompatibility and stability
      of the matrix containing structurally stabilized epidermal growth factor (S-EGF)
      and basic fibroblast growth factor (S-bFGF). RESULTS AND DISCUSSION: We
      stabilized EGF and bFGF that are structurally more stable than existing EGF and
      bFGF. We developed biocompatible matrix using S-EGF, S-bFGF, and hyaluronate-
      collagen dressing (HCD) matrix. The developed matrix, S-EGF and S-bFGF loaded on
      HCD matrix, had no cytotoxicity, in vitro. Also, these matrixes had longer
      releasing period that result in enhancement of half-life. Finally, when these
      matrixes were applied on the wound of diabetic mice, there were no inflammatory
      responses, in vivo. Thus, our results demonstrate that these matrixes are
      biologically safe and biocompatible as wound-dressing material. CONCLUSIONS: Our
      stabilized EGF and bFGF was more stable than existing EGF and bFGF and the HCD
      matrix had the capacity to efficiently deliver growth factors. Thus, the S-EGF
      and S-bFGF loaded on HCD matrix had improved stability. Therefore, these matrixes
      may be suitable for impaired wound healing, resulting in application of clinical
      treatment.

PMID- 27042332
TI  - An exceptionally preserved Eocene shark and the rise of modern predator-prey
      interactions in the coral reef food web.
AB  - BACKGROUND: Following extreme climatic warming events, Eocene Lagerstatten
      document aquatic and terrestrial vertebrate faunas surprisingly similar to modern
      counterparts. This transition in marine systems is best documented in the
      earliest teleost-dominated coral reef assemblage of Pesciara di Bolca, northern
      Italy, from near the end of the Eocene Climatic Optimum. Its rich fauna shows
      similarities with that of the modern Great Barrier Reef in niche exploitation by
      and morphological disparity among teleost primary consumers. However, such
      paleoecological understanding has not transcended trophic levels above primary
      consumers, particularly in carcharhiniform sharks. RESULTS: We report an
      exceptionally preserved fossil school shark (Galeorhinus cuvieri) from Pesciara
      di Bolca. In addition to the spectacular preservation of soft tissues, including
      brain, muscles, and claspers, this male juvenile shark has stomach contents
      clearly identifiable as a sphyraenid acanthomorph (barracuda). This association
      provides evidence that a predator-prey relationship between Galeorhinus and
      Sphyraena in the modern coral reefs has roots in the Eocene. A growth curve of
      the living species of Galeorhinus fitted to G. cuvieri suggests that all
      specimens of G. cuvieri from the lagoonal deposits of Bolca represent sexually
      and somatically immature juveniles. CONCLUSION: The modern trophic association
      between higher-degree consumers (Galeorhinus and Sphyraena) has a counterpart in
      the Eocene Bolca, just as Bolca and the Great Barrier Reef show parallels among
      teleost primary consumers. Given the age of Bolca, trophic networks among
      consumers observed in modern coral reefs arose by the exit from the Climatic
      Optimum. The biased representation of juveniles suggests that the Bolca
      Lagerstatte served as a nursery habitat for G. cuvieri. Ultraviolet photography
      may be useful in probing for exceptional soft tissue preservation before common
      acid preparation methods.

PMID- 27042333
TI  - Therapeutic and diagnostic outcomes of a standardised, comprehensive care pathway
      for patients with systemic sclerosis.
AB  - OBJECTIVES: To determine the outcomes, including number of medical interventions
      and initiation of immunosuppressive treatment of a standardised, comprehensive,
      diagnostic care pathway for patients with systemic sclerosis (SSc). Patient
      characteristics associated with need for medical interventions and with need for
      immunosuppressive treatment were determined. METHODS: Data were routinely
      gathered in connection with a 2-day care pathway combining multidisciplinary care
      and complete diagnostic work-up of organ involvement in SSc. The number of
      patients in whom the pathway resulted in medical interventions, and/or initiation
      of immunosuppressives was recorded. Patient characteristics and diagnostic tests
      results were compared between patients with and without medical interventions,
      and patients with and without initiation of immunosuppressives by means of
      multivariable logistic regression analyses. RESULTS: During a period of 44
      months, 226 patients with SSc were referred to the care pathway. They included
      186 (82%) women with mean age of 54 (SD 14.5) years, and median disease duration
      of 4 years (range 1-11); 73 (32%) of them had diffuse cutaneous SSc. Medical
      interventions were initiated in 191 (85%) patients, including initiation of
      immunosuppressive treatment in n=49 (22%). Presence of telangiectasias and higher
      erythrocyte sedimentation rate were associated with any medical intervention. Of
      commonly available variables, lower age, higher skin score and absence of
      anticentromere antibody were associated with initiation of immunosuppressives.
      CONCLUSIONS: A standardised comprehensive 2-day care pathway for patients with
      SSc resulted in additional diagnostic or therapeutic interventions in 85% of the
      patients, regardless of SSc subtype and disease duration. In 22% of the patients,
      immunosuppressive treatment was initiated.

PMID- 27042334
TI  - Patient-initiated appointments compared with standard outpatient care for
      rheumatoid arthritis: a randomised controlled trial.
AB  - OBJECTIVES: To test the hypothesis that implementing a patient-initiated system
      of care could improve clinical outcome in rheumatoid arthritis (RA) using disease
      activity guided management. METHODS: An 18-month controlled blinded end point two
      centre study with 131 patients with RA randomised to intervention (n=64) or
      control (n=67). The intervention group participants were guaranteed appointments
      to a rheumatologist within 10 working days if they subjectively experienced a
      flare in disease activity. The control group participants were booked in advance
      according to guidelines. Independent assessments were performed in the two groups
      at 0, 3, 6, 12 and 18 months. Outcome measures included: Disease Activity Score
      28 (DAS28), a Visual Analogue Scale (satisfaction with care, confidence in care),
      number of appointments with a rheumatologist. RESULTS: DAS28 decreased. Median
      satisfaction and confidence in care were >90 mm on Visual Analog Scale. Median
      number of appointments was 3. There were no significant differences between the
      groups among these outcomes. Visits in the intervention group more often resulted
      in change of treatment than in the control group (p<0.001). CONCLUSIONS: Patient
      initiated care was neither better nor inferior to traditional care in terms of
      outcomes analysed. Patient-initiated appointments can safely be used in everyday
      outpatient care of RA to empower the patient, if disease activity guided
      management is applied. Further research should investigate if this intervention
      can target a subgroup of patients and hence also result in released resources.

PMID- 27042335
TI  - Glucocorticoids and chronotherapy in rheumatoid arthritis.
AB  - It is evident that the morning symptoms of rheumatoid arthritis (RA) are linked
      to the circadian abnormal increase in night inflammation, favoured by inadequate
      cortisol secretion under conditions of active disease. Therefore, exogenous
      glucocorticoid treatment is recommended in RA at low doses since it may partially
      act like a 'replacement therapy'. The prevention/treatment of the night
      upregulation of the immune/inflammatory reaction (and related flare of cytokine
      synthesis) has been shown to be more effective when exogenous glucocorticoid
      administration is obtained with a night-time-release formulation. Large-scale
      trials documented that modified-release prednisone has greater efficacy then
      morning prednisone for long-term low-dose glucocorticoid treatment in patients
      with RA, showing at least a more significant reduction in morning joint
      stiffness. Interestingly, despite a considerably higher cost than conventional
      prednisone, chronotherapy with night-time-release prednisone was recognised as a
      cost-effective option for patients with RA not on glucocorticoids who are
      eligible for therapy with biological disease-modifying antirheumatic drugs
      (DMARDs). Moreover, since different cell populations involved in the inflammatory
      process are particularly activated during the night, other therapeutical
      approaches used in RA, for example, conventional DMARDs and non-steroidal anti
      inflammatory drugs (NSAIDs), should follow the same concepts of glucocorticoid
      chronotherapy. Indeed, bedtime methotrexate chronotherapy was found to improve RA
      symptoms compared to the current standard dosing methods, and several available
      NSAIDs (ie, indomethacin, aceclofenac, ketoprofen, flurbiporfen, lornoxicam) have
      been very recently modified in their formulation, in order to obtain
      chronotherapeutical effects in RA. 

PMID- 27042336
TI  - Predictive value of tender joints compared to synovitis for structural damage in
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the predictive value of tender joints compared to
      synovitis for structural damage in rheumatoid arthritis (RA). METHODS: A post hoc
      analysis was performed on a prospective 2-year study of 59 patients with active
      RA starting on antitumour necrosis factor (TNF). Tenderness and synovitis was
      assessed clinically at baseline, followed by blinded ultrasound assessment (B
      mode and power Doppler ultrasound (PDUS)) on the hands and feet (2 wrists, 10
      metacarpophalangeal, 10 proximal interphalangeal and 10 metatarsophalangeal (MTP)
      joints). Radiographs of these joints were performed at baseline and at 2 years.
      The risk of radiographic progression with respect to the presence of baseline
      tenderness or synovitis, as well as its persistence (after 4 months of anti-TNF),
      was estimated by OR (95% CI). RESULTS: Baseline tender joints were the least
      predictive for radiographic progression (OR=1.53 (95% CI 1.02 to 2.29) p<0.04),
      when compared to synovitis (clinical OR=2.08 (95% CI 1.39 to 3.11) p<0.001 or
      PDUS OR=1.80 (95% CI 1.20 to 2.71) p=0.005, respectively). Tender joints with the
      presence of synovitis were predictive of radiographic progression (OR=1.89 (95%
      CI 1.25 to 2.85) p=0.002), especially seen in the MTP joints. Non-tender joints
      with no synovitis were negatively predictive (OR=0.57 (95% CI 0.39 to 0.82)
      p=0.003). Persistence of tender joints was negatively predictive (OR=0.38 (95% CI
      0.18 to 0.78) p=0.009) while persistence of synovitis was predictive (OR=2.41
      (95% CI 1.24 to 4.67) p=0.01) of radiographic progression. CONCLUSIONS: Synovitis
      is better than tenderness to predict for subsequent structural progression.
      However, coexistence of tenderness and synovitis at the level of an individual
      joint is predictive of structural damage, particularly in the MTP joints. TRIAL
      REGISTRATION NUMBER: NCT00444691.

PMID- 27042337
TI  - Association of the different types of radiographic damage with physical function
      in patients with rheumatoid arthritis: analysis of the RAPID trials.
AB  - OBJECTIVES: To evaluate the separate effects of erosions (E) (bone damage), joint
      space narrowing (JSN) (cartilage loss) and (sub)luxation (SLUX) (soft tissue
      damage) in four different joint groups on physical disability in rheumatoid
      arthritis (RA). METHODS: 3-year follow-up data from the Rheumatoid Arthritis
      PreventIon of structural Damage (RAPID) 1 and 2 trials were used. These
      randomised controlled trials compared certolizumab plus methotrexate (MTX) versus
      MTX in patients with RA. Physical function was measured by Health Assessment
      Questionnaire (HAQ). Radiographic damage was measured by the van der Heijde
      modified Sharp score; separate scores for E, JSN and SLUX were available.
      Generalised estimating equations were performed to assess the relationship
      between HAQ and E, JSN and SLUX scores, separately and in all joint groups.
      RESULTS: In separate models for each type of damage and after adjusting for age,
      gender, baseline disease activity and treatment group, E and JSN were more
      strongly associated with HAQ than with SLUX. In combined models, JSN was the only
      type of lesion associated with HAQ when all joints were included together. When
      separate joint groups were analysed, E in the wrist and JSN in the
      metacarpophalangeal joints (MCPs) were most strongly associated with function.
      CONCLUSIONS: Among RA-related joint damage, cartilage loss quantified by JSN is
      an important determinant of physical function. However, when analysing joint
      groups separately, erosive damage in the wrist and JSN in the MCPs had the most
      important influence on disability. These data indicate that the comprehensive
      assessment of joint damage is needed to reliably reflect disease-related damage.

PMID- 27042338
TI  - Long-term healthcare use and costs in patients with stable coronary artery
      disease: a population-based cohort using linked health records (CALIBER).
AB  - AIMS: To examine long-term healthcare utilization and costs of patients with
      stable coronary artery disease (SCAD). METHODS AND RESULTS: Linked cohort study
      of 94 966 patients with SCAD in England, 1 January 2001 to 31 March 2010,
      identified from primary care, secondary care, disease, and death registries.
      Resource use and costs, and cost predictors by time and 5-year cardiovascular
      disease (CVD) risk profile were estimated using generalized linear models.
      Coronary heart disease hospitalizations were 20.5% in the first year and 66% in
      the year following a non-fatal (myocardial infarction, ischaemic or haemorrhagic
      stroke) event. Mean healthcare costs were L3133 per patient in the first year and
      L10 377 in the year following a non-fatal event. First-year predictors of cost
      included sex (mean cost L549 lower in females), SCAD diagnosis (non-ST-elevation
      myocardial infarction cost L656 more than stable angina), and co-morbidities
      (heart failure cost L657 more per patient). Compared with lower risk patients (5
      year CVD risk 3.5%), those of higher risk (5-year CVD risk 44.2%) had higher 5
      year costs (L23 393 vs. L9335) and lower lifetime costs (L43 020 vs. L116 888).
      CONCLUSION: Patients with SCAD incur substantial healthcare utilization and
      costs, which varies and may be predicted by 5-year CVD risk profile. Higher risk
      patients have higher initial but lower lifetime costs than lower risk patients as
      a result of shorter life expectancy. Improved cardiovascular survivorship among
      an ageing CVD population is likely to require stratified care in anticipation of
      the burgeoning demand.

PMID- 27042339
TI  - RECOMBINANT BCL-XL ATTENUATES VASCULAR HYPERPERMEABILITY IN A RAT MODEL OF
      HEMORRHAGIC SHOCK.
AB  - Following hemorrhagic shock (HS), vascular hyperpermeability i.e. the leakage of
      fluid, nutrients and proteins into the extravascular space occurs primarily due
      to the disruption of the endothelial cell-cell adherens junctional complex.
      Studies from our laboratory demonstrate that activation of the mitochondria
      mediated 'intrinsic' apoptotic signaling cascade has a significant role in
      modulating HS-induced hyperpermeability. Here we report the novel use of
      recombinant Bcl-xL, an anti-apoptotic protein, to control HS-induced vascular
      hyperpermeability. Our results corroborate involvement of vascular
      hyperpermeability and apoptotic signaling. Hemorrhagic shock (HS) (mean arterial
      pressure [MAP] was reduced to 40 mmHg for 60 minutes followed by resuscitation to
      90 mmHg for 60 minutes) in rats resulted in vascular hyperpermeability as
      determined by intra-vital microscopy. Treatment of Bcl-xL (2.5ug/ml of rat blood
      in non-lipid cationic polymer, i.v.) before, during and even after HS attenuated
      or reversed HS-induced vascular hyperpermeability significantly (p<0.05).
      Conversely, treatment using Bcl-xL inhibitors, 2-methoxy antimycin (2-MeOAA) and
      ABT 737, significantly increased vascular hyperpermeability compared to sham
      (p<0.05). Bcl-xL treatment also decreased the amount of fluid volume required to
      maintain a MAP of 90 mmHg during resuscitation (p<0.05). HS resulted in increased
      mitochondrial ROS formation, reduction of DeltaPsim, mitochondrial release of
      cytochrome c and significant activation of caspase-3 (p<0.05). All of these
      effects were significantly inhibited by Bcl-xL pre-treatment (p<0.05). Our
      results show that recombinant Bcl-xL is effective against HS-induced vascular
      hyperpermeability that appears to be mediated through preservation of DeltaPsim
      and subsequent prevention of caspase-3 activation.

PMID- 27042340
TI  - Improved outcomes on subcutaneous IgG in patients with humoral immunodeficiency
      and co-morbid bowel disease.
AB  - Immunoglobulin replacement can be life-saving for certain individuals with
      immunodeficiencies. Subcutaneous IgG (SCIG) is an increasingly used method of
      replacement over intravenous IgG (IVIG), with potential advantages including
      fewer systemic side effects, no need for IV access, patient-reported improved
      quality of life, and decreased cost. However, while patients with certain
      associated co-morbidities, such as protein-losing enteropathy, may demonstrate
      more stable IgG levels when on SCIG compared to IVIG, the clinical significance
      of these experiences is not well described. Using retrospective chart review, we
      examined three cases in which SCIG and IVIG was administered to patients with
      either common variable immunodeficiency (CVID) or secondary humoral
      immunodeficiency and protein-losing gastrointestinal co-morbid disease. Both
      outpatient and inpatient records were reviewed for data regarding treatment with
      IVIG versus SCIG, reported frequency and severity of infections,
      hospitalizations, and IgG levels. All three patients demonstrated improvement in
      infection rate, stability of IgG levels, and co-morbid disease when on SCIG as
      compared to IVIG. These findings suggest that the pharmacokinetics of SCIG may
      translate into more consistent serum IgG levels, contributing to clinical
      improvement in immunodeficient patients with protein-losing comorbidities when
      compared to IVIG. Limitations to this study are small patient numbers,
      retrospective design, and potential therapeutic bias. Further characterization of
      the effects of co-morbid conditions on immunoglobulin replacement is critical to
      providing improved and informed patient care.

PMID- 27042341
TI  - Quality of Sulfadoxine-Pyrimethamine Given as Antimalarial Prophylaxis in
      Pregnant Women in Selected Health Facilities in Central Region of Ghana.
AB  - The use of sulfadoxine-pyrimethamine (SP) as an intermittent preventive treatment
      (IPT) against malaria during pregnancy has become a policy in most sub-Sahara
      African countries and crucially depends on the efficacy of SP. This study sets
      out to evaluate the effectiveness of the SP given to the pregnant women in some
      selected health facilities in the Central Region of Ghana to prevent maternal
      malaria in pregnant women. A total of 543 pregnant women recruited from 7
      selected health centres in Central Region of Ghana participated in the study.
      Parasite density of Plasmodium falciparum was determined from peripheral blood of
      the pregnant women using microscopy. High performance liquid chromatography
      (HPLC) and dissolution tester were used to determine the quality of the SP.
      Malaria infection was recorded in 11.2% of pregnant women who had a history of SP
      consumption. SP failed the dissolution test. Pregnant women who did not receive
      IPT-SP were 44%. Low haemoglobin level was recorded in 73.5% of the pregnant
      women. The results indicated that SP was substandard. IPT-SP is ineffective in
      preventing malaria infection. 

PMID- 27042342
TI  - A Meta-Analysis of Studies Evaluating Visual and Anatomical Outcomes in Patients
      with Treatment Resistant Neovascular Age-Related Macular Degeneration following
      Switching to Treatment with Aflibercept.
AB  - With the introduction of aflibercept, eyes with neovascular age-related macular
      degeneration (AMD) not responding well to injections of ranibizumab or
      bevacizumab can be switched to treatment with aflibercept. We carried out a meta
      analysis to analyze all available evidence of visual and anatomical outcomes of
      eyes with resistant neovascular AMD switched to aflibercept at six months. Data
      from seven retrospective and prospective studies looking at change in best
      corrected visual acuity (BCVA) and central retinal thickness (CRT) were included.
      Weighted mean difference (WMD) and 95% CI were estimated using the standardized
      mean change method. The overall results of the meta-analysis showed a small but
      statistically significant improvement in BCVA six months following treatment
      switch to aflibercept (WMD 0.142, 95% CI 0.006 to 0.28; p = 0.04), and the effect
      was more significant in data gathered from prospective studies (WMD 0.407, 95% CI
      0.023 to 0.791, p = 0.038). There was a significant improvement in CRT following
      treatment switch to aflibercept (WMD -0.36, 95% CI -0.485 to -0.235; p < 0.0001).
      Our meta-analysis indicates that following treatment switch to aflibercept
      patients may have a significant improvement in CRT with stabilization or even
      some improvement in their visual acuity. 

PMID- 27042343
TI  - Review: The Lacrimal Gland and Its Role in Dry Eye.
AB  - The human tear film is a 3-layered coating of the surface of the eye and a loss,
      or reduction, in any layer of this film may result in a syndrome of blurry vision
      and burning pain of the eyes known as dry eye. The lacrimal gland and accessory
      glands provide multiple components to the tear film, most notably the aqueous.
      Dysfunction of these glands results in the loss of aqueous and other products
      required in ocular surface maintenance and health resulting in dry eye and the
      potential for significant surface pathology. In this paper, we have reviewed
      products of the lacrimal gland, diseases known to affect the gland, and
      historical and emerging dry eye therapies targeting lacrimal gland dysfunction. 

PMID- 27042344
TI  - Microarrays as Model Biosensor Platforms to Investigate the Structure and
      Affinity of Aptamers.
AB  - Immobilization of nucleic acid aptamer recognition elements selected free in
      solution onto the surface of biosensor platforms has proven challenging. This
      study investigated the binding of multiple aptamer/target pairs immobilized on a
      commercially available microarray as a model system mimicking biosensor
      applications. The results indicate a minimum distance (linker length) from the
      surface and thymine nucleobase linker provides reproducible binding across
      varying conditions. An indirect labeling method, where the target was labeled
      with a biotin followed by a brief Cy3-streptavidin incubation, provided a higher
      signal-to-noise ratio and over two orders of magnitude improvement in limit of
      detection, compared to direct Cy3-protein labeling. We also showed that the
      affinities of the aptamer/target interaction can change between direct and
      indirect labeling and conditions to optimize for the highest fluorescence
      intensity will increase the sensitivity of the assay but will not change the
      overall affinity. Additionally, some sequences which did not initially bind
      demonstrated binding when conditions were optimized. These results, in
      combination with studies demonstrating enhanced binding in nonselection buffers,
      provided insights into the structure and affinity of aptamers critical for
      biosensor applications and allowed for generalizations in starting conditions for
      researchers wishing to investigate aptamers on a microarray surface. 

PMID- 27042345
TI  - Blood Lactate Is a Useful Indicator for the Medical Emergency Team.
AB  - Lactate has been thoroughly studied and found useful for stratification of
      patients with sepsis, in the Intensive Care Unit, and trauma care. However,
      little is known about lactate as a risk-stratification marker in the Medical
      Emergency Team- (MET-) call setting. We aimed to determine whether the arterial
      blood lactate level at the time of a MET-call is associated with increased 30-day
      mortality. This is an observational study on a prospectively gathered cohort at a
      regional secondary referral hospital. All MET-calls during the two-year study
      period were eligible. Beside blood lactate, age and vital signs were registered
      at the call. Among the 211 calls included, there were 64 deaths (30.3%). Median
      lactate concentration at the time of the MET-call was 1.82 mmol/L (IQR 1.16-2.7).
      We found differences between survivors and nonsurvivors for lactate and oxygen
      saturation, a trend for age, but no significant correlations between mortality
      and systolic blood pressure, respiratory rate, and heart rate. As compared to
      normal lactate (<2.44 mmol/L), OR for 30-day mortality was 3.54 (p < 0.0006) for
      lactate 2.44-5.0 mmol/L and 4.45 (p < 0.0016) for lactate > 5.0 mmol/L. The
      present results support that immediate measurement of blood lactate in MET call
      patients is a useful tool in the judgment of illness severity. 

PMID- 27042346
TI  - A Possible Role of Anhedonia as Common Substrate for Depression and Anxiety.
AB  - Depression and anxiety are often comorbid, in up to 70% of cases, and the level
      of one or the other may fluctuate, leading now to a diagnosis of depression, now
      to a diagnosis of anxiety. For these reasons, and for the presence of many other
      common factors, it has been suggested that both are part of the same continuum of
      problems and that they have a common substrate. This paper proposes the
      possibility that anhedonia may be an important component of this possible common
      substrate, and it tries to identify the mechanism with which anhedonia could
      contribute to causing both depression and anxiety. It also proposes an
      explanation why an intense pleasure could improve both depression and anxiety. 

PMID- 27042347
TI  - Psychometric Limitations of the Center for Epidemiologic Studies-Depression Scale
      for Assessing Depressive Symptoms among Adults with HIV/AIDS: A Rasch Analysis.
AB  - The Center for Epidemiological Studies-Depression (CES-D) scale is a widely used
      measure of depressive symptoms, but its psychometric properties have not been
      adequately evaluated among adults with HIV/AIDS. This study used an item response
      theory approach (Rasch analysis) to evaluate the CES-D's validity and reliability
      in relation to key demographic and clinical variables in adults with HIV/AIDS. A
      convenience sample of 347 adults with HIV/AIDS (231 males, 93 females, and 23
      transgenders; age range 22-77 years) completed the CES-D. A Rasch model
      application was used to analyze the CES-D's rating scale functioning, internal
      scale validity, person-response validity, person-separation validity, internal
      consistency, differential item functioning (DIF), and differential test
      functioning. CES-D scores were generally high and associated with several
      demographic and clinical variables. The CES-D distinguished 3 distinct levels of
      depression and had acceptable internal consistency but lacked unidimensionality,
      five items demonstrated poor fit to the model, 15% of the respondents
      demonstrated poor fit, and eight items demonstrated DIF related to gender, race,
      or AIDS diagnosis. Removal of misfitting items resulted in minimal improvement in
      the CES-D's substantive and structural validity. CES-D scores should be
      interpreted with caution in adults with HIV/AIDS, particularly when comparing
      scores across gender and racial groups. 

PMID- 27042348
TI  - Calcium and Vitamin D Supplement Prescribing Practices among Providers Caring for
      Children with Autism Spectrum Disorders: Are We Addressing Bone Health?
AB  - Children with autism spectrum disorders (ASD) have several risk factors for low
      bone mineral density. The gluten-free, casein-free (GFCF) diet is a complementary
      therapy sometimes used in ASD that raises concerns for the adequacy of calcium
      and vitamin D intake. This study evaluated the prescribing practices of calcium
      and vitamin D supplements and the practice of checking 25-hydroxy vitamin D
      (25(OH)D) levels by providers in 100 children with ASD, 50 of whom were on the
      GFCF diet. Fifty-two percent and 46% of children on the GFCF diet were on some
      form of vitamin D and calcium supplements, respectively, compared to 18% and 14%
      of those not on this diet. Twenty-four percent of children in the GFCF group had
      a documented 25(OH)D level compared to none in the non-GFCF group. The data
      highlight a gap in calcium and vitamin D supplement prescribing practices among
      providers caring for children with ASD as well as a gap in the practice of
      checking 25(OH)D levels. 

PMID- 27042349
TI  - Trajectories of Change in Obesity among Tehranian Families: Multilevel Latent
      Growth Curve Modeling.
AB  - Objectives. To evaluate the trajectories of change in obesity within and between
      Tehranian families, who participated in the Tehran Lipid and Glucose Study
      (TLGS). Methods. This study is a family-based longitudinal design, in four waves.
      A total of 14761 individuals, within 3980 families, were selected. Three
      anthropometric measurements, body mass index (BMI), waist circumference (WC), and
      a body shape index (ABSI), were recorded. Multilevel latent growth curve modeling
      (MLGCM) approach was used for evaluating the change trajectories in obesity
      within and between the families. Results. The mean age of the subjects in the
      present study was 33.28 +/- 19.01 (range 3-89 years) and 50.1% were male. Obesity
      was significantly increased (P < 0.001). Individuals with more fat become obese
      slower, whereas families with more fat become obese faster (P < 0.001). The
      initial value and growth rate of WC and ABSI were greater in men than in women,
      while this result is contrary to BMI (P < 0.001). Conclusions. Our findings
      demonstrated that there is an alarming increase in the obesity trend in Tehranian
      families. The important role of the family in the prevention of obesity is
      highlighted, underlining the need for public health programs, as family centered
      educations to lifestyle modification, which can address this emerging crisis. 

PMID- 27042350
TI  - Matrix Metalloproteinases and Subclinical Atherosclerosis in Chronic Kidney
      Disease: A Systematic Review.
AB  - Background. Cardiovascular disease (CVD) remains a significant problem in Chronic
      Kidney Disease (CKD). Subclinical atherosclerosis identified by noninvasive
      methods could improve CVD risk prediction in CKD but these methods are often
      unavailable. We therefore systematically reviewed whether circulating levels of
      Matrix Metalloproteinases (MMPs) and tissue inhibitors (TIMPs) are associated
      with subclinical atherosclerosis in CKD, as this would support their use as
      biomarkers or pharmacologic targets. Methods. All major electronic databases were
      systematically searched from inception until May 2015 using appropriate terms.
      Studies involving CKD patients with data on circulating MMPs levels and
      atherosclerosis were considered and subjected to quality assessment. Results.
      Overall, 16 studies were identified for qualitative synthesis and 9 studies were
      included in quantitative synthesis. MMP-2 and TIMP-1 were most frequently studied
      while most studies assessed carotid Intima-Media Thickness (cIMT) as a measure of
      subclinical atherosclerosis. Only MMP-2 demonstrated a consistent positive
      association with cIMT. Considerable variability in cIMT measurement methodology
      and poor plaque assessment was found. Conclusions. Although MMPs demonstrate
      great potential as biomarkers of subclinical atherosclerosis, they are
      understudied in CKD and not enough data existed for meta-analysis. Larger studies
      involving several MMPs, with more homogenized approaches in determining the
      atherosclerotic burden in CKD, are needed. 

PMID- 27042351
TI  - Optimism and Mortality in Older Men and Women: The Rancho Bernardo Study.
AB  - Purpose. To examine the associations of optimism and pessimism with all-cause,
      cardiovascular disease (CVD), coronary heart disease (CHD), and cancer mortality
      in a population-based sample of older men and women followed <=12 years. Methods.
      367 men and 509 women aged >=50 from the Rancho Bernardo Study attended a 1999
      2002 research clinic visit when demographic, behavioral, and medical history were
      obtained and completed a 1999 mailed survey including the Life Orientation Test
      Revised (LOT-R). Mortality outcomes were followed through 2012. Results. Average
      age at baseline was 74.1 years; during follow-up (mean = 8.1 years), 198
      participants died, 62 from CVD, 22 from CHD, and 49 from cancer. Total LOT-R,
      optimism and pessimism scores were calculated. Participants with the highest
      optimism were younger and reported less alcohol use and smoking and more
      exercise. Cox proportional hazard models showed that higher total LOT-R and
      optimism, but not pessimism scores, were associated with reduced odds of CHD
      mortality after adjusting for age, sex, alcohol, smoking, obesity, physical
      exercise, and medication (HR = 0.86, 95% CI = 0.75, 0.99; HR = 0.77, 95% CI =
      0.61, 0.99, resp.). No associations were found for all-cause, CVD, or cancer
      mortality. Conclusions. Optimism was associated with reduced CHD mortality in
      older men and women. The association of positive attitudes with mortality merits
      further study. 

PMID- 27042352
TI  - Influenza A Virus and Influenza B Virus Can Induce Apoptosis via Intrinsic or
      Extrinsic Pathways and Also via NF-kappaB in a Time and Dose Dependent Manner.
AB  - Influenza viruses are able to cause annual epidemics and pandemics due to their
      mutation rates and reassortment capabilities leading to antigenic shifts and
      drifts. To identify host response to influenza A and B viruses on A549 and MDCK
      II cells at low and high MOIs, expressions of MxA and caspases 3, 8, and 9 and
      BAD, TNFalpha, and IkappaBalpha genes were measured in the cells supernatants.
      H1N1 and H3N2 prefer to initially enhance the intrinsic pathway, determined by
      higher caspase 9 activity in MDCK II cells compared to caspase 8 activity and
      vice versa in A549 cells at different MOIs, while INF B prefers extrinsic pathway
      in A549 cells according to significant low or undetectable caspase 9 activity and
      high activity of caspase 8 but also can induce intrinsic pathway in MDCK II cells
      as determined by significant low or undetectable activity of caspase 8 and high
      caspase 9 activity at different MOIs; the considerable MxA expression was found
      in influenza A and B viruses infected A549 and MDCK II cells at low MOIs. In
      conclusion, influenza A and B viruses induced extrinsic and intrinsic apoptosis
      in parallel, and the induction was associated with viral infection in a dose
      dependent manner. 

PMID- 27042353
TI  - Biosensors in Health Care: The Milestones Achieved in Their Development towards
      Lab-on-Chip-Analysis.
AB  - Immense potentiality of biosensors in medical diagnostics has driven scientists
      in evolution of biosensor technologies and innovating newer tools in time. The
      cornerstone of the popularity of biosensors in sensing wide range of biomolecules
      in medical diagnostics is due to their simplicity in operation, higher
      sensitivity, ability to perform multiplex analysis, and capability to be
      integrated with different function by the same chip. There remains a huge
      challenge to meet the demands of performance and yield to its simplicity and
      affordability. Ultimate goal stands for providing point-of-care testing facility
      to the remote areas worldwide, particularly the developing countries. It entails
      continuous development in technology towards multiplexing ability, fabrication,
      and miniaturization of biosensor devices so that they can provide lab-on-chip
      analysis systems to the community. 

PMID- 27042354
TI  - The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide
      Nanoparticles in Adult Male Rats.
AB  - The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic
      herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin,
      kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200
      300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium
      chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0
      mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs
      group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h
      later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was
      performed using Student's t-test for grouped data with ANOVA posttest. The GbE
      protected renal cells against the effects of TiO2-NPs because it reversed the
      increased activity of gamma-glutamyltranspeptidase and the enzymatic activity of
      dipeptidylaminopeptidase IV at all times tested (0-5, 5-24, 24-48, and 48-72 h).
      Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three
      times tested (5-24, 24-48, and 48-72). Thus, we conclude that GbE has a
      beneficial activity in the cytoplasmic membranes of brush border cells on the
      renal tubules, against the adverse effects that can be produced by some
      xenobiotics in this case the TiO2-NPs, in experimental rats. 

PMID- 27042355
TI  - Changes in Sediment Fatty Acid Composition during Passage through the Gut of
      Deposit Feeding Holothurians: Holothuria atra (Jaeger, 1883) and Holothuria
      leucospilota (Brandt, 1835).
AB  - Sea cucumbers Holothuria atra and Holothuria leucospilota play an important role
      in the bioturbation of sediment in coral reef and rocky intertidal ecosystems.
      This study investigated changes in sediment fatty acid (FA) composition during
      gut passage in H. atra and H. leucospilota. The FA composition did not differ
      significantly between species. Comparison of FA composition in ambient sediment
      (AS), foregut (FG), midgut (MG), hindgut (HG), and faecal pellets (FPs) indicated
      that marked changes in FA composition occurred during passage through the gut of
      H. atra and H. leucospilota. Saturated fatty acids (SAFAs), monounsaturated fatty
      acids (MUFAs), polyunsaturated fatty acids (PUFAs), and branched fatty acids
      (BrFAs) were significantly higher in FG than in AS, suggesting that both species
      selectively ingested nutrient rich particles. Significant reduction of SAFAs,
      MUFAs, PUFAs, and BrFAs occurred in MD and HD, with complete elimination of most
      PUFAs in FPs. A decrease in PUFAs 20:5omega3, 18:4omega3, 22:5omega3, 22:6omega3,
      18:2omega6, 18:3omega3, 18:3omega6, odd-numbered BrFAs, and MUFA 18:1omega7
      indicated that algal detritus and bacteria were important part of diet. These
      results have implications for the fate of specific dietary FAs, especially omega3
      and omega6, and the contribution holothurian FPs make to the FA composition of
      coral reef and rocky intertidal ecosystems. 

PMID- 27042356
TI  - Genotype Cluster Analysis in Pathogenic Escherichia coli Isolates Producing
      Different CDT Types.
AB  - Diarrheagenic and uropathogenic E. coli types are mainly characterized by the
      expression of distinctive bacterial virulent factors. stx1, stx2 (Shiga toxins),
      and cdt (cytolethal distending toxin) genes have been acquired by horizontal gene
      transfer. Some virulent genes such as espP (serine protease), etpD (part of
      secretion pathway), and katP (catalase-peroxidase), or sfpA gene (Sfp fimbriae),
      are on plasmids and the others like fliC (flagellin) and the fimH gene (fimbriae
      type-I) are located on chromosome. Genomic pathogenicity islands (PAIs) carry
      some virulent genes such as hly gene. To determine the existence of virulence
      genes in cdt clinical isolates, genes including stx1, stx2, cdt, hly, espP, katP,
      sfpA, etpD, fliC, and fimH were assessed by Polymerase Chain Reaction (PCR). The
      most prevalent isolates for etpD and katP genes were 85.7% in cdtII. katP gene
      was also observed 83.3% in cdtI. However, in 42.85% of cdtIII isolates, espP gene
      was the most detected. Moreover, hly gene was also the most prominent gene in
      cdtIII (71.42%). sfpA gene was observed in 66.6% of cdtV. stx1 gene was detected
      in 100% of cdtII, cdtIV, and cdtV types. Presence and pattern of virulence genes
      were considered among cdt positive isotypes and used for their clustering and
      profiling. 

PMID- 27042357
TI  - Unique AGG Interruption in the CGG Repeats of the FMR1 Gene Exclusively Found in
      Asians Linked to a Specific SNP Haplotype.
AB  - Fragile X syndrome (FXS) is the most common inherited intellectual disability. It
      is caused by the occurrence of more than 200 pure CGG repeats in the FMR1 gene.
      Normal individuals have 6-54 CGG repeats with two or more stabilizing AGG
      interruptions occurring once every 9- or 10-CGG-repeat blocks in various
      populations. However, the unique (CGG)6AGG pattern, designated as 6A, has been
      exclusively reported in Asians. To examine the genetic background of AGG
      interruptions in the CGG repeats of the FMR1 gene, we studied 8 SNPs near the CGG
      repeats in 176 unrelated Thai males with 19-56 CGG repeats. Of these 176 samples,
      we identified AGG interruption patterns from 95 samples using direct DNA
      sequencing. We found that the common CGG repeat groups (29, 30, and 36) were
      associated with 3 common haplotypes, GCGGATAA (Hap A), TTCATCGC (Hap C), and
      GCCGTTAA (Hap B), respectively. The configurations of 9A9A9, 10A9A9, and 9A9A6A9
      were commonly found in chromosomes with 29, 30, and 36 CGG repeats, respectively.
      Almost all chromosomes with Hap B (22/23) carried at least one 6A pattern,
      suggesting that the 6A pattern is linked to Hap B and may have originally
      occurred in the ancestors of Asian populations. 

PMID- 27042358
TI  - The Impact of Sleep Timing, Sleep Duration, and Sleep Quality on Depressive
      Symptoms and Suicidal Ideation amongst Japanese Freshmen: The EQUSITE Study.
AB  - Aim. The aim of this study was to identify the impact of bedtime, wake time,
      sleep duration, sleep-onset latency, and sleep quality on depressive symptoms and
      suicidal ideation amongst Japanese freshmen. Methods. This cross-sectional data
      was derived from the baseline survey of the Enhancement of Q-University Students
      Intelligence (EQUSITE) study conducted from May to June, 2010. A total of 2,631
      participants were recruited and completed the following self-reported
      questionnaires: the Pittsburgh Sleep Quality Index (PSQI), the Center for
      Epidemiologic Studies Depression Scale (CES-D), and the original Health Support
      Questionnaires developed by the EQUSITE study research team. Results. Of 1,992
      participants eligible for analysis, 25.5% (n = 507) reported depressive symptoms
      (CES-D total score >= 16), and 5.8% (n = 115) reported suicidal ideation. The
      present study showed that late bedtime (later than 01:30), sleep-onset latency
      (>=30 minutes), and poor sleep quality showed a marginally significant
      association with depressive symptoms. Poor sleep quality was seen to predict
      suicidal ideation even after adjusting for depressive symptoms. Conclusion. The
      current study has important implications for the role of bedtime in the
      prevention of depressive symptoms. Improving sleep quality may prevent the
      development of depressive symptoms and reduce the likelihood of suicidal
      ideation. 

PMID- 27042359
TI  - Effects of Sex and Mild Intrainsult Hypothermia on Neuropathology and Neural
      Reorganization following Neonatal Hypoxic Ischemic Brain Injury in Rats.
AB  - Hypoxia ischemia (HI) is a recognized risk factor among late-preterm infants,
      with HI events leading to varied neuropathology and cognitive/behavioral
      deficits. Studies suggest a sex difference in the incidence of HI and in the
      severity of subsequent behavioral deficits (with better outcomes in females).
      Mechanisms of a female advantage remain unknown but could involve sex-specific
      patterns of compensation to injury. Neuroprotective hypothermia is also used to
      ameliorate HI damage and attenuate behavioral deficits. Though currently
      prescribed only for HI in term infants, cooling has potential intrainsult
      applications to high-risk late-preterm infants as well. To address this important
      clinical issue, we conducted a study using male and female rats with a postnatal
      (P) day 7 HI injury induced under normothermic and hypothermic conditions. The
      current study reports patterns of neuropathology evident in postmortem tissue.
      Results showed a potent benefit of intrainsult hypothermia that was comparable
      for both sexes. Findings also show surprisingly different patterns of
      compensation in the contralateral hemisphere, with increases in hippocampal
      thickness in HI females contrasting reduced thickness in HI males. Findings
      provide a framework for future research to compare and contrast mechanisms of
      neuroprotection and postinjury plasticity in both sexes following a late-preterm
      HI insult. 

PMID- 27042360
TI  - Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in
      Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS).
AB  - Tinnitus is the phantom perception of sound in the absence of an acoustic
      stimulus. To date, the purported neural correlates of tinnitus from animal models
      have not been adequately characterized with translational technology in the human
      brain. The aim of the present study was to measure changes in oxy-hemoglobin
      concentration from regions of interest (ROI; auditory cortex) and non-ROI
      (adjacent nonauditory cortices) during auditory stimulation and silence in
      participants with subjective tinnitus appreciated equally in both ears and in
      nontinnitus controls using functional near-infrared spectroscopy (fNIRS). Control
      and tinnitus participants with normal/near-normal hearing were tested during a
      passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI
      under episodic periods of auditory stimulation with 750 or 8000 Hz tones,
      broadband noise, and silence. During periods of silence, tinnitus participants
      maintained increased hemodynamic responses in ROI, while a significant
      deactivation was seen in controls. Interestingly, non-ROI activity was also
      increased in the tinnitus group as compared to controls during silence. The
      present results demonstrate that both auditory and select nonauditory cortices
      have elevated hemodynamic activity in participants with tinnitus in the absence
      of an external auditory stimulus, a finding that may reflect basic science neural
      correlates of tinnitus that ultimately contribute to phantom sound perception.

PMID- 27042361
TI  - Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease.
AB  - Near complete infiltration of the liver secondary to metastasis from the head and
      neck cancer is a rare occurrence. The prognosis of liver failure associated with
      malignant infiltration is extremely poor; the survival time of patients is
      extremely low. We present a case of acute warfarin toxicity as initial
      manifestation of metastatic liver disease. Our patient is a 64-year-old woman
      presenting with epigastric pain and discomfort, found to have unrecordable
      International Normalized Ratio. She rapidly deteriorated with acute respiratory
      failure requiring mechanical ventilation, profound shock requiring high dose
      vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening
      of lactic acidosis and severe metabolic abnormalities, and refractory to
      aggressive supportive care and died in less than 48 hours. Autopsy revealed that
      >90% of the liver was replaced by tumor masses. 

PMID- 27042362
TI  - Chairside Fabrication of an All-Ceramic Partial Crown Using a Zirconia-Reinforced
      Lithium Silicate Ceramic.
AB  - The chairside fabrication of a monolithic partial crown using a zirconia
      reinforced lithium silicate (ZLS) ceramic is described. The fully digitized model
      free workflow in a dental practice is possible due to the use of a powder-free
      intraoral scanner and the computer-aided design/computer-assisted manufacturing
      (CAD/CAM) of the restorations. The innovative ZLS material offers a singular
      combination of fracture strength (>370 Mpa), optimum polishing characteristics,
      and excellent optical properties. Therefore, this ceramic is an interesting
      alternative material for monolithic restorations produced in a digital workflow. 

PMID- 27042363
TI  - Removal of a Tungsten Carbide Ring from the Finger of a Pregnant Patient: A Case
      Report Involving 2 Emergency Departments and the Internet.
AB  - Introduction. Destructive or nondestructive procedures may be used to remove
      rings from injured fingers. Because of their hardness, tungsten carbide rings
      present special problems. Case Presentation. The patient was a 33-year-old woman,
      two weeks before delivery, with a swollen and reddened ring finger. It was
      decided to remove a tungsten carbide ring from her ring finger. This was achieved
      by shattering the ring with locking pliers. The patient's ring finger recovered
      fully. 

PMID- 27042364
TI  - Hashimoto's Thyroiditis and Graves' Disease in One Patient: The Extremes of
      Thyroid Dysfunction Associated with Interferon Treatment.
AB  - Autoimmune thyroid disease associated with interferon therapy can manifest as
      destructive thyroiditis, Graves' Hyperthyroidism, and autoimmune (often
      subclinical) hypothyroidism, the latter persisting in many patients. There are
      scare reports of a single patient developing extremes of autoimmune thyroid
      disease activated by the immunomodulatory effects of interferon. A 60-year-old
      man received 48 weeks of pegylated interferon and ribavirin therapy for chronic
      HCV. Six months into treatment, he reported fatigue, weight gain, and slowed
      cognition. Serum thyroid stimulating hormone (TSH) was 58.8 mIU/L [0.27-4.2], fT4
      11.1 pmol/L [12-25], and fT3 4.2 pmol/L [2.5-6.0] with elevated anti-TPO (983
      IU/mL [<35]) and anti-TG (733 U/mL [<80]) antibodies. He commenced thyroxine with
      initial clinical and biochemical resolution but developed symptoms of
      hyperthyroidism with weight loss and tremor 14 months later. Serum TSH was <0.02
      mIU/L, fT4 54.3 pmol/L, and fT3 20.2 pmol/L, with an elevated TSH receptor (TRAb,
      4.0 U/L [<1.0]), anti-TPO (1,163 IU/mL) and anti-TG (114 U/mL) antibodies.
      Technetium scan confirmed Graves' Disease with bilateral diffuse increased tracer
      uptake (5.9% [0.5-3.5%]). The patient commenced carbimazole therapy for 6 months.
      Treatment was ceased following spontaneous clinical and biochemical remission
      (TSH 3.84 mIU/L, fT4 17pmol/L, fT3 4.5 pmol/L, and TRAb <1 U/L). This raises the
      need to monitor thyroid function closely in patients both during and following
      completion of interferon treatment. 

PMID- 27042365
TI  - Peculiar Presentation of Ulcerative Colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory and recurrent disorder that is
      characterized by bowel inflammation. Among the extraintestinal manifestations
      (EIMs) that associate UC are the joints and renal manifestations. Joint affection
      in the form of arthritis can precede the intestinal manifestations of UC.
      However, renal affection with amyloidosis does not precede the UC diagnosis.
      Herein, we report a case of 26-year-old male diagnosed with UC after having
      peripheral arthritis for long time in addition to spondylitis and kidney
      amyloidosis. 

PMID- 27042366
TI  - Gastric and Duodenal Pseudomelanosis: An Extended Unusual Finding in a Patient
      with End Stage Kidney Disease.
AB  - Gastric and duodenal pseudomelanosis is a rare endoscopic mucosal finding,
      characterized by the accumulation of iron in macrophages of the lamina propria of
      the stomach and duodenum. The clinical significance and long term sequelae have
      not been clarified yet. However, this benign condition is associated with a
      variety of clinical conditions, such as essential hypertension, chronic renal
      failure, diabetes mellitus, long term intake of iron supplements, and furosemide.
      Duodenal pseudomelanosis appears to be more common than gastric pseudomelanosis
      given the fact that a few cases of gastric pseudomelanosis have been reported in
      the literature so far. We report a case of 88-year-old lady with ESRD who is
      maintained on hemodialysis and presented with abdominal pain. An upper GI
      endoscopy showed discoloration of the antrum of the stomach and most portion of
      her duodenum. Histopathology report confirmed the presence of iron laden
      macrophages in the lamina propria of both stomach and duodenum. 

PMID- 27042367
TI  - A Case of Advanced Descending Colon Cancer in an Adult Patient with Intestinal
      Malrotation.
AB  - This report presents an operative case of advanced descending colon cancer in an
      adult patient with intestinal malrotation. A 63-year-old Japanese male was
      suffering from left side abdominal pain, abdominal distension, and constipation.
      An endoscopic examination revealed an advanced tumor in the descending colon.
      Computed tomography (CT) of the abdomen revealed the thickening of the descending
      colon wall and superior mesenteric vein rotation. An opaque enema detected severe
      stenosis of the descending colon. An abdominal X-ray examination revealed the
      dilation of the colon and small intestine with niveau. At the insertion of an
      ileus tube, the C-loop of the duodenum was observed to be absent and the small
      intestine was located on the right side of the abdomen. After the decompression
      of the bowel contents, laparotomy was performed. Descending colon cancer was
      observed to have directly invaded the left side of the transverse colon. Left
      hemicolectomy, lymph node dissection, and appendectomy were performed. The
      patient had an uneventful recovery and was discharged from the hospital on the
      16th day after surgery. This report presents a rare operative case of descending
      colon cancer in an adult patient with intestinal malrotation. 

PMID- 27042368
TI  - Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis
      and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline
      Hyperbilirubinemia.
AB  - Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of
      these patients were taking concurrent ribavirin presenting elevated unconjugated
      hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with
      elevated bilirubin level have also been reported in patients with decompensated
      cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia
      and recently diagnosed compensated cirrhosis due to chronic hepatitis C
      infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum
      HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She
      was considered as illegible for pegylated-interferon-free treatment with direct
      acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination
      for twelve weeks was planned. Hyperbilirubinemia developed from the beginning
      with peak values during the 3rd month of treatment. However, no findings of liver
      decompensation were noticed. Hyperbilirubinemia was benign and fully reversible
      and our patient finally achieved sustained virological response 24 weeks after
      the end of treatment. 

PMID- 27042369
TI  - A Case of Brucellosis with Recurrent Attacks of Vasculitis.
AB  - Brucellosis is a zoonosis that affects several organs or systems. Skin
      involvement is nonspecific and it is reported to range between 0,4 and 17% of the
      patients with brucellosis. Here, we defined a 36-year-old female patient
      presented to our clinic with a clinical picture of recurrent attacks of
      vasculitis due to brucellosis for the first time. Skin involvement and vasculitic
      lesions as a finding of skin involvement are nonspecific in brucellosis.
      Therefore, in the regions like Turkey where brucellosis is endemic, brucellosis
      should be kept in mind necessarily in the differential diagnosis of vasculitis. 

PMID- 27042370
TI  - Bronchogenic Carcinoma with Cardiac Invasion Simulating Acute Myocardial
      Infarction.
AB  - Cardiac metastases in bronchogenic carcinoma may occur due to retrograde
      lymphatic spread or by hematogenous dissemination of tumour cells, but direct
      invasion of heart by adjacent malignant lung mass is very uncommon. Pericardium
      is frequently involved in direct cardiac invasion by adjacent lung cancer.
      Pericardial effusion, pericarditis, and tamponade are common and life threatening
      presentation in such cases. But direct invasion of myocardium and endocardium is
      very uncommon. Left atrial endocardium is most commonly involved in such cases
      due to anatomical contiguity with pulmonary hilum through pulmonary veins, and in
      most cases left atrial involvement is asymptomatic. But myocardial compression
      and invasion by adjacent lung mass may result in myocardial ischemia and may
      present with retrosternal, oppressive chest pain which clinically may simulate
      with the acute myocardial infarction (AMI). As a result, it leads to misdiagnosis
      and delayed diagnosis of lung cancer. Here we report a case of non-small-cell
      carcinoma of right lung which was presented with asymptomatic invasion in left
      atrium and retrosternal chest pain simulating AMI due to myocardial compression
      by adjacent lung mass, in a seventy-four-year-old male smoker. 

PMID- 27042371
TI  - A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia.
AB  - Background. Epithelial dysplasia is categorized as conjunctival/corneal
      intraepithelial neoplasia which is a precancerous lesion. The lesion is usually
      developed at the limbal region and grows towards central cornea in association
      with neovascularization into the lesion. Here, we report a case of isolated
      nonvascularized corneal epithelial dysplasia surrounded by normal corneal
      epithelium with immune histochemical finding of ocular surface tissues
      cytokeratins, for example, keratin 13 and keratin 12. Case Presentation. A 76
      year-old man consulted us for visual disturbance with localized opacification of
      the corneal epithelium in his left eye. His visual acuity was 20/20 and 20/200 in
      his right and left eye, respectively. Slit lamp examination showed a whitish
      plaque-like lesion at the center of his left corneal epithelium. No vascular
      invasion to the lesion was found. The lesion was surgically removed and subjected
      to histopathological examination and diagnosed as epithelial dysplasia.
      Amyloidosis was excluded by direct fast scarlet 4BS (DFS) staining.
      Immunohistochemistry showed that the dysplastic epithelial cells express keratin
      13 and vimentin, but not keratin 12, indicating that the neoplastic epithelial
      cells lacked corneal-type epithelium differentiation. Conclusions. The lesion was
      diagnosed as nonvascularized epithelial dysplasia of ocular surface. Etiology of
      the lesion is not known. 

PMID- 27042372
TI  - Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid
      Fractures-Apropos of Two Cases.
AB  - Purpose. Anderson type III odontoid fractures have traditionally been considered
      stable and treated conservatively. However, unstable cases with unfavorable
      results following conservative treatment have been reported. Methods. We present
      the cases of two patients who sustained minimally displaced Anderson type III
      fractures with a characteristic fracture pattern that we refer to as "oblique
      type axis body fracture." Results. The female patients aged 90 and 72 years,
      respectively, were both diagnosed with minimally displaced Anderson type III
      fractures. Both fractures had a characteristic "oblique type" fracture pattern.
      The first patient was treated conservatively with cervical spine immobilization
      in a semirigid collar. However, gross displacement was noted at the 6-week follow
      up visit. The second patient was therefore treated operatively by C1-C3/4
      posterior fusion and the course was uneventful. Conclusions. Oblique type axis
      body fractures resemble a highly unstable subtype of Anderson type III fractures
      with the potential of severe secondary deformity following conservative
      treatment, irrespective of initial grade of displacement. The authors therefore
      warrant a high index of suspicion for this injury and suggest early operative
      stabilization. 

PMID- 27042373
TI  - Adult Onset Still's Disease: A Review on Diagnostic Workup and Treatment Options.
AB  - Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease of
      unknown etiology and pathogenesis that presents in 5 to 10% of patients as fever
      of unknown origin (FUO) accompanied by systemic manifestations. We report an
      interesting case of a 33-year-old African-American male who presented with one
      month duration of FUO along with skin rash, sore throat, and arthralgia. After
      extensive workup, potential differential diagnoses were ruled out and the patient
      was diagnosed with AOSD based on the Yamaguchi criteria. The case history,
      incidence, pathogenesis, clinical manifestations, differential diagnoses,
      diagnostic workup, treatment modalities, and prognosis of AOSD are discussed in
      this case report. 

PMID- 27042374
TI  - T-Bar Utilization for Concomitant Coronary Artery Bypass Graft Operation and Left
      Upper Lobectomy.
AB  - Management in patients with coexisting coronary artery disease and lung carcinoma
      is usually a two-stage operation, with the cardiac surgery procedure followed by
      pulmonary resection at a later time. Delayed tumor resection on the other hand
      may be detrimental. Off-pump coronary artery bypass grafting could facilitate
      concomitant lung resection at one stage via median sternotomy. T-bar retractor
      may be a useful tool in the surgical approach of this combined operation. 

PMID- 27042375
TI  - Immunological and Clinical Responses following the Use of Antiretroviral Therapy
      among Elderly HIV-Infected Individuals Attending Care and Treatment Clinic in
      Northwestern Tanzania: A Retrospective Cohort Study.
AB  - Background. Limited information exists on adults >=50 years receiving HIV care in
      sub-Saharan Africa despite their increasing number. We aimed at studying
      immunologic and clinical responses to ART in this population. Methods. Data of
      patients who initiated HAART between 30th of June 2004 and 1st of May 2008 at
      Sekou Toure Care and Treatment Clinic were retrospectively analyzed. Date of ART
      initiation was used as a baseline and 48 months as a follow-up date. Immune
      recovery was defined as a CD4 count of >=350 cells/mm(3) at 48 months and late
      presentation as presentation with WHO stage 3 or 4 at clinic enrollment.
      Proportions of patients reaching this endpoint were compared between the two
      groups. Results. A total of 728 patients were included in our study; of these 73
      (10.0%) were aged 50 years and above. Late presentation was more common in
      elderly patients than young patients (65.7% versus 56.1%, P = 0.12). Proportion
      of patients with CD4 count >=350 (immune recovery) was higher in younger patients
      than in elderly patients, although this was not statistically significant (54.5%
      versus 44.9%, P = 0.2). Median absolute increase in CD4 at 48 months was higher
      in younger patients than in elderly patients (+241.5 cells/mm(3) versus +146
      cells/mm(3), P = 0.007). Conclusion. Elderly HIV patients have higher rates of
      late presentation, with lower immune recovery. Strategies to increase HIV testing
      in this group are required for early diagnosis and treatment to improve outcomes.

PMID- 27042376
TI  - Improving Access to Malaria Rapid Diagnostic Test in Niger State, Nigeria: An
      Assessment of Implementation up to 2013.
AB  - Nigeria's 2009-2013 malaria strategic plan adopted WHO diagnosis and treatment
      guidelines, which include the use of rapid diagnostic tests (RDTs) prior to
      prescribing treatment with artemisinin combination therapies (ACTs). The current
      study explores accessibility barriers to the use of RDTs in Niger State and makes
      recommendations for improving the uptake of RDTs. The study employs literature
      review, review of data from the Niger State Health Management Information System
      for January-October 2013, and application of Peters' conceptual framework for
      assessing access to health services. Data showed that 27 percent of public health
      facilities (HFs) implemented RDTs, with the aid of donor funds. In these
      facilities, 77 percent of fever cases presented during the study period were
      tested with RDTs; 53 percent of fever cases were confirmed cases of malaria,
      while 60 percent of fever cases were treated. Stockouts of RDTs were a major
      constraint, and severe fever tended to trigger presumptive treatment. We conclude
      that although implementation of RDTs led to a reduction in the use of ACTs at
      HFs, more substantial reduction could be achieved if the state government
      directed more resources towards the acquisition of RDTs as well as raising the
      level of awareness of potential users. 

PMID- 27042377
TI  - Simultaneous Quantification of Dexpanthenol and Resorcinol from Hair Care
      Formulation Using Liquid Chromatography: Method Development and Validation.
AB  - The current study presents the simultaneous quantification of dexpanthenol and
      resorcinol from marketed hair care formulation. Dexpanthenol is often present as
      an active ingredient in personal care products for its beautifying and
      invigorating properties and restorative and smoothing properties. On the other
      hand resorcinol is mainly prescribed for the treatment of seborrheic dermatitis
      of scalp. The toxic side effects of resorcinol limit its use in dermatological
      preparations. Therefore an accurate quantification technique for the simultaneous
      estimation of these two components can be helpful for the formulation industries
      for the accurate analysis of their product quality. In the current study a high
      performance liquid chromatographic technique has been developed using a C18
      column and a mobile phase consisting of phosphate buffer of pH = 2.8 following a
      gradient elution. The mobile phase flow rate was 0.6 mL per minute and the
      detection wavelength was 210 nm for dexpanthenol and 280 nm for resorcinol. The
      linearity study was carried out using five solutions having concentrations
      ranging between 10.34 MUg.mL(-1) and 82.69 MUg.mL(-1) (r (2) = 0.999) for
      resorcinol and 10.44 MUg.mL(-1) and 83.50 MUg.mL(-1) (r (2) = 0.998) for
      dexpanthenol. The method has been validated as per ICH Q2(R1) guidelines. The
      ease of single step sample preparation, accuracy, and precision (intraday and
      interday) study presents the method suitable for the simultaneous quantification
      of dexpanthenol and resorcinol from any personal care product and dermatological
      preparations containing these two ingredients. 

PMID- 27042378
TI  - Impact of Organic and Conventional Systems of Coffee Farming on Soil Properties
      and Culturable Microbial Diversity.
AB  - A study was undertaken with an objective of evaluating the long-term impacts of
      organic (ORG) and conventional (CON) methods of coffee farming on soil physical,
      chemical, biological, and microbial diversity. Electrical conductivity and bulk
      density were found to increase by 34% and 21%, respectively, in CON compared to
      ORG system, while water holding capacity was found decreased in both the systems.
      Significant increase in organic carbon was observed in ORG system. Major
      nutrients, nitrogen and potassium, levels showed inclination in both ORG and CON
      system, but the trend was much more pronounced in CON system. Phosphorus was
      found to increase in both ORG and CON system, but its availability was found to
      be more with CON system. In biological attributes, higher soil respiration and
      fluorescein diacetate activity were recorded in ORG system compared to CON
      system. Higher soil urease activity was observed in CON system, while
      dehydrogenase activity does not show significant differences between ORG and CON
      systems. ORG system was found to have higher macrofauna (31.4%), microbial
      population (34%), and microbial diversity indices compared to CON system. From
      the present study, it is accomplished that coffee soil under long-term ORG system
      has better soil properties compared to CON system. 

PMID- 27042379
TI  - Response of Pea Varieties to Damage Degree of Pea Weevil, Bruchus pisorum L.
AB  - A study was conducted to determine the response of five pea varieties (Pisum
      sativum L.) to damage degree of Bruchus pisorum: Glyans, Modus, Kamerton, and
      Svit (Ukrainian cultivars) and Pleven 4 (Bulgarian cultivar). The seeds were
      classified into three types: healthy seeds (type 1), damaged seeds with
      parasitoid emergence hole (type 2), and damaged seeds with bruchid emergence hole
      (type 3) and they were sown. It was found that the weight of 1000 seeds did not
      affect the field germination of the pea varieties. Healthy and damaged seeds with
      parasitoid emergence holes (first and second seed types) provide a very good
      opportunity for growth and development while plants from damaged seeds with
      bruchid emergence holes had poor germination and vigor and low productivity.
      These seeds cannot provide the creation of well-garnished seeding and stable crop
      yields. Among tested varieties, the Ukrainian variety Glyans had considerably
      higher seed weight, field germination, and index germination and weak egg-laying
      activity of B. pisorum compared to others. Use of spring pea cultivars that are
      weakly preferred by the pea weevil in breeding programs would reduce losses due
      to pea weevil and provide an environmentally safer option to its control. 

PMID- 27042380
TI  - Association of oxidative stress with mortality: the Beaver Dam Eye Study.
AB  - Epidemiological studies have shown that oxidative stress is associated with
      cardiovascular disease (CVD) and diabetes. However, the association of oxidative
      stress marker with non-CVD and CVD mortality has not been extensively evaluated.
      The association of baseline serum 8-isoprostane (8-ISO) with all-cause, non-CVD,
      and CVD mortality was examined in a random subset (n = 1,753) of a population
      based study of 4,926 adults (99% non-Hispanic whites; 56% women) aged 43-86 years
      from the Beaver Dam Eye Study. Cause of death was ascertained by death
      certificate between 1987 and 2002. 8-ISO was measured by immunoassay. Cox
      proportional hazards regression analysis was used to estimate mortality hazard
      ratios (HRs) and 95% confidence intervals (CIs) by one 8-ISO standard deviation.
      During a median follow-up of 13.1 years, 590 (33.7%) participants died (290 CVD
      deaths). After adjusting for socio-demographics and CVD risk factors, 8-ISO was
      significantly associated with all-cause (HR = 1.1, 95% CI 1.01-1.2) and non-CVD
      (HR = 1.14, 95% CI 1.01-1.28) mortality but not with CVD mortality (HR = 1.06,
      95% CI 0.93-1.2). When limited to participants with BMI < 25 kg/m2, individuals
      in the highest 8-ISO quartile had approximately 34 to 36% increased risk of all
      cause, non-CVD, and CVD death compared to those at the lowest quartile. In
      contrast, 8-ISO was not significantly associated with mortality among those with
      BMI >= 25 kg/m2. These findings suggest that baseline serum 8-ISO, a marker of
      oxidative stress, is an independent risk factor of all-cause, non-CVD, and CVD
      mortality among a cohort of middle-aged adults with normal BMI.

PMID- 27042381
TI  - Disability, Poverty, and Material Hardship since the Passage of the ADA.
AB  - The past 25 years have seen an unprecedented expansion in formal civil rights for
      people with disabilities that, among other things, was predicted to improve their
      economic well-being. Studies of economic well-being among people with
      disabilities have traditionally focused on employment and earnings, despite the
      fact that a minority of people with disabilities are employed. More recent
      literature has expanded to include measures of income poverty and material
      hardship, but has not examined trends in these dimensions of economic well-being
      over time or across different groups of people with disabilities. The current
      study uses nationally representative data covering the 1993-2010 period to
      examine trends over time in cross-sectional and dynamic measures of income
      poverty, and multiple dimensions of material hardship. It also describes
      differences in time trends by education, sex, race/ethnicity, and employment
      status among people with disabilities in income poverty and any material
      hardship. Levels of both material hardship and income poverty are high across the
      entire period for all groups, but while material hardship remains at the same
      level between 1993 and 2010, income poverty declines. These findings show that
      there has been little improvement over the past two decades in the economic well
      being of people with disabilities, and additional research is needed to
      understand the mechanisms that keep even groups that are relatively privileged -
      college graduates and full-time, full-year workers - at very low levels of
      economic well-being.

PMID- 27042383
TI  - Incorporating Diblock Copolymer Nanoparticles into Calcite Crystals: Do Anionic
      Carboxylate Groups Alone Ensure Efficient Occlusion?
AB  - New spherical diblock copolymer nanoparticles were synthesized via RAFT aqueous
      dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) at 70  degrees C
      and 20% w/w solids using either poly(carboxybetaine methacrylate) or poly(proline
      methacrylate) as the steric stabilizer block. Both of these stabilizers contain
      carboxylic acid groups, but poly(proline methacrylate) is anionic above pH 9.2,
      whereas poly(carboxybetaine methacrylate) has zwitterionic character at this pH.
      When calcite crystals are grown at an initial pH of 9.5 in the presence of these
      two types of nanoparticles, it is found that the anionic poly(proline
      methacrylate)-stabilized particles are occluded uniformly throughout the crystals
      (up to 6.8% by mass, 14.0% by volume). In contrast, the zwitterionic
      poly(carboxybetaine methacrylate)-stabilized particles show no signs of occlusion
      into calcite crystals grown under identical conditions. The presence of
      carboxylic acid groups alone therefore does not guarantee efficient occlusion:
      overall anionic character is an additional prerequisite.

PMID- 27042382
TI  - Implementing Child-focused Activity Meter Utilization into the Elementary School
      Classroom Setting Using a Collaborative Community-based Approach.
AB  - INTRODUCTION: The prevalence of pediatric obesity has increased over the past 3
      decades and is a pressing public health program. New technology advancements that
      can encourage more physical in children are needed. The Zamzee program is an
      activity meter linked to a motivational website designed for children 8-14 years
      of age. The objective of the study was to use a collaborative approach between a
      medical center, the private sector and local school staff to assess the
      feasibility of using the Zamzee Program in the school-based setting to improve
      physical activity levels in children. METHODS: This was a pilot 8-week
      observational study offered to all children in one fifth grade classroom. Body
      mass index (BMI), the amount of physical activity by 3-day recall survey, and
      satisfaction with usability of the Zamzee Program were measured pre- and post
      study. RESULTS: Out of 11 children who enrolled in the study, 7 completed all
      study activities. In those who completed the study, the median (interquartile
      range) total activity time by survey increased by 17 (1042) minutes and the BMI
      percentile change was 0 (8). Both children and their caregivers found the Zamzee
      Activity Meter (6/7) and website (6/7) "very easy" or "easy" to use. CONCLUSION:
      The Zamzee Program was found to be usable but did not significantly improve
      physical activity levels or BMI. Collaborative obesity intervention projects
      involving medical centers, the private sector and local schools are feasible but
      the effectiveness needs to be evaluated in larger-scale studies.

PMID- 27042384
TI  - Electrodeposition of Gold to Conformally Fill High Aspect Ratio Nanometric
      Silicon Grating Trenches: A Comparison of Pulsed and Direct Current Protocols.
AB  - Filling high-aspect-ratio trenches with gold is a frequent requirement in the
      fabrication of x-ray optics as well as micro-electronic components and other
      fabrication processes. Conformal electrodeposition of gold in sub-micron-width
      silicon trenches with an aspect ratio greater than 35 over a grating area of
      several square centimeters is challenging and has not been described in the
      literature previously. A comparison of pulsed plating and constant current
      plating led to a gold electroplating protocol that reliably filled trenches for
      such structures.

PMID- 27042385
TI  - Microscale vicariance and diversification of Western Balkan caddisflies linked to
      karstification.
AB  - The karst areas in the Dinaric region of the Western Balkan Peninsula are a
      hotspot of freshwater biodiversity. Many investigators have examined
      diversification of the subterranean freshwater fauna in these karst systems.
      However, diversification of surface-water fauna remains largely unexplored. We
      assessed local and regional diversification of surface-water species in karst
      systems and asked whether patterns of population differentiation could be
      explained by dispersal-diversification processes or allopatric diversification
      following karst-related microscale vicariance. We analyzed mitochondrial
      cytochrome c oxidase subunit I (mtCOI) sequence data of 4 caddisfly species
      (genus Drusus) in a phylogeographic framework to assess local and regional
      population genetic structure and Pliocene/Pleistocene history. We used BEAST
      software to assess the timing of intraspecific diversification of the target
      species. We compared climate envelopes of the study species and projected
      climatically suitable areas during the last glacial maximum (LGM) to assess
      differences in the species climatic niches and infer potential LGM refugia. The
      haplotype distribution of the 4 species (324 individuals from 32 populations) was
      characterized by strong genetic differentiation with few haplotypes shared among
      populations (16%) and deep divergence among populations of the 3 endemic species,
      even at local scales. Divergence among local populations of endemics often
      exceeded divergence among regional and continental clades of the widespread D.
      discolor. Major divergences among regional populations dated to 2.0 to 0.5 Mya.
      Species distribution model projections and genetic structure suggest that the
      endemic species persisted in situ and diversified locally throughout multiple
      Pleistocene climate cycles. The pattern for D. discolor was different and
      consistent with multiple invasions into the region. Patterns of population
      genetic structure and diversification were similar for the 3 regional endemic
      Drusus species and consistent with microscale vicariance after the onset of
      intensified karstification in the Dinaric region. Karstification may induce
      microscale vicariance of running surface-water habitats and probably promotes
      allopatric fragmentation of stream insects at small spatial scales.

PMID- 27042386
TI  - The role of social relationship in HIV healing and its implications in HIV cure
      in China.
AB  - HIV is both a biomedical disease and a social phenomenon that is constructed in
      particular cultural contexts. A successful and humane HIV cure requires not only
      the science of eradicating pathogens, but also the art of healing to restore
      harmony between mind and body. Healing in the context of HIV cure will be both
      personal and interpersonal, biological and social, and will involve rebuilding
      connections between HIV patients and their social environment. Social conceptions
      of healing have been highlighted in many regions with rich non-biomedical healing
      traditions, including China. Based on an adapted theoretical model on social
      relationships and health, we address the essential role of social relations for
      HIV healing in Chinese cultural context, and propose several recommendations for
      reforming practices and policies regarding HIV healing. In general, family is
      still a core social unit in HIV patients' medical journey from diagnosis to
      treatment. A positive patient-physician relationship based on mutual respect and
      trust also has critical impact on patients' physical and mental health.
      Physicians may become a key or the main source of social support in circumstances
      when families are not actively engaged in healing. Reconnecting HIV patients with
      their communities should be a necessary component of HIV cure, as this will help
      patients engage more fully in the HIV healing process. We call for a family
      centered approach in HIV healing intervention to strengthen patient-family ties;
      a series of policies to build up and sustain positive patient-physician ties; and
      multi-level strategies to empower patients and rebuild their bonds to community
      and larger society. We also call for more empirical research on how non
      biomedical healing approaches in various cultural settings could (directly or
      indirectly) inform HIV cure research.

PMID- 27042387
TI  - Gender differences in weight bias internalisation and eating pathology in
      overweight individuals.

PMID- 27042388
TI  - Impaired Retrieval Inhibition of Threat Material in Generalized Anxiety Disorder.
AB  - Generalized Anxiety Disorder (GAD) is characterized by cognitive biases toward
      threat-relevant information, but the underlying mechanisms are unclear. We
      translated a retrieval-practice paradigm from cognitive science to investigate
      impaired inhibition of threat information as one such mechanism. Participants
      diagnosed with GAD and never-disordered control participants learned a series of
      cue-target pairs; whereas some cues were associated only with neutral targets,
      others were associated with both neutral and threat targets. Next, participants
      practiced retrieving neutral targets, which typically suppresses the subsequent
      recall of unpracticed associated targets (retrieval-induced forgetting; RIF).
      Finally, participants were tested on their recall of all targets. Despite showing
      intact RIF of neutral targets, the GAD group failed to exhibit RIF of threat
      targets. Furthermore, within the GAD group, less RIF of threat targets correlated
      with greater pervasiveness of worry. Deficits in inhibitory control over threat
      relevant information may underlie the cognitive pathology of GAD, which has
      important treatment implications.

PMID- 27042389
TI  - Cost-effectiveness of antiviral therapy during late pregnancy to prevent
      perinatal transmission of hepatitis B virus.
AB  - Background. Hepatitis B virus (HBV) infections are perinatally transmitted from
      chronically infected mothers. Supplemental antiviral therapy during late
      pregnancy with lamivudine (LAM), telbivudine (LdT), or tenofovir (TDF) can
      substantially reduce perinatal HBV transmission compared to postnatal
      immunoprophylaxis (IP) alone. However, the cost-effectiveness of these measures
      is not clear. Aim. This study evaluated the cost-effectiveness from a societal
      perspective of supplemental antiviral agents for preventing perinatal HBV
      transmission in mothers with high viral load (>6 log10 copies/mL). Methods. A
      systematic review and network meta-analysis were performed for the risk of
      perinatal HBV transmission with antiviral therapies. A decision analysis was
      conducted to evaluate the clinical and economic outcomes in China of four
      competing strategies: postnatal IP alone (strategy IP), or in combination with
      perinatal LAM (strategy LAM + IP), LdT (strategy LdT + IP), or TDF (strategy TDF
      + IP). Antiviral treatments were administered from week 28 of gestation to 4
      weeks after birth. Outcomes included treatment-related costs, number of
      infections, and quality-adjusted life years (QALYs). One- and two-way sensitivity
      analyses were performed to identify influential clinical and cost-related
      variables. Probabilistic sensitivity analyses were used to estimate the
      probabilities of being cost-effective for each strategy. Results. LdT + IP and
      TDF + IP averted the most infections and HBV-related deaths, and gained the most
      QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs
      with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained
      (95% CI [$932-$20,372]) compared to LAM + IP (GDP per capita for China in 2013
      was $6,800). One-way sensitivity analyses showed that the cost-effectiveness of
      LdT + IP was only sensitive to the relative risk of HBV transmission comparing
      LdT + IP with LAM + IP. Probabilistic sensitivity analyses demonstrated that LdT
      + IP was cost-effective in most cases across willingness-to-pay range of $6,800 ~
      $20,400 per QALY gained. Conclusions. For pregnant HBV-infected women with high
      levels of viremia, supplemental use of LdT during late pregnancy combined with
      postnatal IP for infants is cost-effective in China. 

PMID- 27042390
TI  - Evolution of Philodendron (Araceae) species in Neotropical biomes.
AB  - Philodendron is the second most diverse genus of the Araceae, a tropical monocot
      family with significant morphological diversity along its wide geographic
      distribution in the Neotropics. Although evolutionary studies of Philodendron
      were conducted in recent years, the phylogenetic relationship among its species
      remains unclear. Additionally, analyses conducted to date suggested the inclusion
      of all American representatives of a closely-related genus, Homalomena, within
      the Philodendron clade. A thorough evaluation of the phylogeny and timescale of
      these lineages is thus necessary to elucidate the tempo and mode of evolution of
      this large Neotropical genus and to unveil the biogeographic history of
      Philodendron evolution along the Amazonian and Atlantic rainforests as well as
      open dry forests of South America. To this end, we have estimated the molecular
      phylogeny for 68 Philodendron species, which consists of the largest sampling
      assembled to date aiming the study of the evolutionary affinities. We have also
      performed ancestral reconstruction of species distribution along biomes. Finally,
      we contrasted these results with the inferred timescale of Philodendron and
      Homalomena lineage diversification. Our estimates indicate that American
      Homalomena is the sister clade to Philodendron. The early diversification of
      Philodendron took place in the Amazon forest from Early to Middle Miocene,
      followed by colonization of the Atlantic forest and the savanna-like landscapes,
      respectively. Based on the age of the last common ancestor of Philodendron, the
      species of this genus diversified by rapid radiations, leading to its wide extant
      distribution in the Neotropical region. 

PMID- 27042391
TI  - Spatiotemporal distribution of caudal-type homeobox proteins during development
      of the hindgut and anorectum in human embryos.
AB  - Background. The objectives of this study were to determine the spatiotemporal
      distribution of human caudal-type homeobox proteins CDX1, CDX2 and CDX4 during
      development of the hindgut and anorectum in the embryo and to explore the
      possible roles of CDX genes during morphogenesis of the hindgut and anorectum.
      Methods. Embryos (89) were cut into sections serially and sagittally. From
      gestation weeks 4-9, CDX1, CDX2 and CDX4 proteins were detected on the caudal
      midline by immunohistochemical staining. Results. During week 4, extensive
      immunoreactivity of CDX1, CDX2 and CDX4 was detected in the dorsal urorectal
      septum, urogenital sinus and hindgut. From weeks 5-7, CDX1-, CDX2- and CDX4-
      positive cells were detected mainly in the mesenchyme of the urorectal septum and
      hindgut. The levels of CDX2 and CDX4 immunoreactivity were lower compared to
      CDX1. During weeks 8 and 9, the anorectal epithelium stained positive for CDX1
      and CDX4, and the anal epithelium was positive for CDX2. Conclusions. The CDX
      proteins are constantly distributed during development of the hindgut and
      anorectum and exhibit overlapping distribution patterns in the cloaca/hindgut,
      suggesting they are important in the morphogenesis of the human hindgut and
      anorectum. CDX genes might be involved in development of the anorectal epithelium
      after the rectum has separated from the urorectal septum. 

PMID- 27042392
TI  - Development and characterization of 26 novel microsatellite loci for the trochid
      gastropod Gibbula divaricata (Linnaeus, 1758), using Illumina MiSeq next
      generation sequencing technology.
AB  - In the present study we used the high-throughput sequencing technology Illumina
      MiSeq to develop 26 polymorphic microsatellite loci for the marine snail Gibbula
      divaricata. Four to 32 alleles were detected per locus across 30 samples
      analyzed. Observed and expected heterozygosities ranged from 0.130 to 0.933 and
      from 0.294 to 0.956, respectively. No significant linkage disequilibrium existed.
      Seven loci deviated from Hardy-Weinberg equilibrium that could not totally be
      explained by the presence of null alleles. Sympatric distribution with other
      species of the genus Gibbula, as G. rarilineata and G. varia, lead us to test the
      cross utility of the developed markers in these two species, which could be
      useful to test common biogeographic patterns or potential hybridization
      phenomena, since morphological intermediate specimens were found. 

PMID- 27042393
TI  - Anti-apoptotic response during anoxia and recovery in a freeze-tolerant wood frog
      (Rana sylvatica).
AB  - The common wood frog, Rana sylvatica, utilizes freeze tolerance as a means of
      winter survival. Concealed beneath a layer of leaf litter and blanketed by snow,
      these frogs withstand subzero temperatures by allowing approximately 65-70% of
      total body water to freeze. Freezing is generally considered to be an ischemic
      event in which the blood oxygen supply is impeded and may lead to low levels of
      ATP production and exposure to oxidative stress. Therefore, it is as important to
      selectively upregulate cytoprotective mechanisms such as the heat shock protein
      (HSP) response and expression of antioxidants as it is to shut down majority of
      ATP consuming processes in the cell. The objective of this study was to
      investigate another probable cytoprotective mechanism, anti-apoptosis during
      oxygen deprivation and recovery in the anoxia tolerant wood frog. In particular,
      relative protein expression levels of two important apoptotic regulator proteins,
      Bax and p-p53 (S46), and five anti-apoptotic/pro-survival proteins, Bcl-2, p-Bcl
      2 (S70), Bcl-xL, x-IAP, and c-IAP in response to normoxic, 24 Hr anoxic exposure,
      and 4 Hr recovery stages were assessed in the liver and skeletal muscle using
      western immunoblotting. The results suggest a tissue-specific regulation of the
      anti-apoptotic pathway in the wood frog, where both liver and skeletal muscle
      shows an overall decrease in apoptosis and an increase in cell survival. This
      type of cytoprotective mechanism could be aimed at preserving the existing
      cellular components during long-term anoxia and oxygen recovery phases in the
      wood frog. 

PMID- 27042395
TI  - The sex lives of ctenophores: the influence of light, body size, and self
      fertilization on the reproductive output of the sea walnut, Mnemiopsis leidyi.
AB  - Ctenophores (comb jellies) are emerging as important animals for investigating
      fundamental questions across numerous branches of biology (e.g., evodevo,
      neuroscience and biogeography). A few ctenophore species including, most notably,
      Mnemiopsis leidyi, are considered as invasive species, adding to the significance
      of studying ctenophore ecology. Despite the growing interest in ctenophore
      biology, relatively little is known about their reproduction. Like most
      ctenophores, M. leidyi is a simultaneous hermaphrodite capable of self
      fertilization. In this study, we assess the influence of light on spawning, the
      effect of body size on spawning likelihood and reproductive output, and the cost
      of self-fertilization on egg viability in M. leidyi. Our results suggest that M.
      leidyi spawning is more strongly influenced by circadian rhythms than specific
      light cues and that body size significantly impacts spawning and reproductive
      output. Mnemiopsis leidyi adults that spawned alone produced a lower percentage
      of viable embryos versus those that spawned in pairs, suggesting that self
      fertilization may be costly in this species. These results provide insight into
      the reproductive ecology of M. leidyi and provide a fundamental resource for
      researchers working with them in the laboratory. 

PMID- 27042394
TI  - A molecular classification of human mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal
      tissue repair, and increasingly adopted for cell therapy, despite the lack of
      consensus on the identity of these cells. In part this is due to the lack of
      specificity of MSC markers. Distinguishing MSC from other stromal cells such as
      fibroblasts is particularly difficult using standard analysis of surface
      proteins, and there is an urgent need for improved classification approaches.
      Transcriptome profiling is commonly used to describe and compare different cell
      types; however, efforts to identify specific markers of rare cellular subsets may
      be confounded by the small sample sizes of most studies. Consequently, it is
      difficult to derive reproducible, and therefore useful markers. We addressed the
      question of MSC classification with a large integrative analysis of many public
      MSC datasets. We derived a sparse classifier (The Rohart MSC test) that
      accurately distinguished MSC from non-MSC samples with >97% accuracy on an
      internal training set of 635 samples from 41 studies derived on 10 different
      microarray platforms. The classifier was validated on an external test set of
      1,291 samples from 65 studies derived on 15 different platforms, with >95%
      accuracy. The genes that contribute to the MSC classifier formed a protein
      interaction network that included known MSC markers. Further evidence of the
      relevance of this new MSC panel came from the high number of Mendelian disorders
      associated with mutations in more than 65% of the network. These result in
      mesenchymal defects, particularly impacting on skeletal growth and function. The
      Rohart MSC test is a simple in silico test that accurately discriminates MSC from
      fibroblasts, other adult stem/progenitor cell types or differentiated stromal
      cells. It has been implemented in the www.stemformatics.org resource, to assist
      researchers wishing to benchmark their own MSC datasets or data from the public
      domain. The code is available from the CRAN repository and all data used to
      generate the MSC test is available to download via the Gene Expression Omnibus or
      the Stemformatics resource. 

PMID- 27042396
TI  - Dramatyping: a generic algorithm for detecting reasonable temporal correlations
      between drug administration and lab value alterations.
AB  - According to the World Health Organization, one of the criteria for the
      standardized assessment of case causality in adverse drug reactions is the
      temporal relationship between the intake of a drug and the occurrence of a
      reaction or a laboratory test abnormality. This article presents and describes an
      algorithm for the detection of a reasonable temporal correlation between the
      administration of a drug and the alteration of a laboratory value course. The
      algorithm is designed to process normalized lab values and is therefore
      universally applicable. It has a sensitivity of 0.932 for the detection of lab
      value courses that show changes in temporal correlation with the administration
      of a drug and it has a specificity of 0.967 for the detection of lab value
      courses that show no changes. Therefore, the algorithm is appropriate to screen
      the data of electronic health records and to support human experts in revealing
      adverse drug reactions. A reference implementation in Python programming language
      is available. 

PMID- 27042397
TI  - Non-adaptive territory selection by a bird with exceptionally long parental care.
AB  - High-quality territories are expected to provide greater fitness return for
      breeding individuals and, thus, are likely to have higher long-term occupation
      rate in comparison to low-quality territories. However, if environmental and
      ecological cues used for territory selection cannot reliably predict true
      territory quality, a mismatch between preferences and fitness may occur. We
      suggest that this kind of non-adaptive territory selection is more likely in
      species with long reproductive cycles, as a long time interval between territory
      establishment and young fledgling should reduce predictability of conditions
      during the critical stages of brood care. In this study, we investigated
      adaptiveness of territory selection in a migratory bird with exceptionally long
      parental care, the mute swan Cygnus olor, which requires over four months to
      complete the entire reproductive cycle from egg laying to young fledging. For
      this purpose, we collected information on the long-term (10-19 years) occupancy
      of 222 swan breeding territories and correlated it with reproductive performance
      (n = 1,345 breeding attempts) and body condition of breeding adults. We found
      that long-term occupancy positively correlated with the timing of breeding,
      suggesting that individuals settled earlier in the attractive, frequently
      occupied territories. By contrast, we found no relationship between territory
      occupancy and reproductive output (hatching and fledging success) or adult body
      condition. The results indicate that at the time of territory selection swans
      might not be able to reliably assess territory quality, likely due to: (1)
      exceptionally long period of parental care, which reduces temporal correlation
      between the conditions at the time of territory selection and conditions during
      chick rearing; and (2) unpredictability of human-related activities that had a
      major impact on reproductive output of swan pairs in our population. 

PMID- 27042398
TI  - Birth Control in Clinical Trials: Industry Survey of Current Use Practices,
      Governance, and Monitoring.
AB  - The Health and Environmental Sciences Institute (HESI) Developmental and
      Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry
      survey on current industry practices for contraception use during clinical
      trials. The objectives of the survey were to improve our understanding of the
      current industry practices for contraception requirements in clinical trials, the
      governance processes set up to promote consistency and/or compliance with
      contraception requirements, and the effectiveness of current contraception
      practices in preventing pregnancies during clinical trials. Opportunities for
      improvements in current practices were also considered. The survey results from
      12 pharmaceutical companies identified significant variability among companies
      with regard to contraception practices and governance during clinical trials.
      This variability was due primarily to differences in definitions, areas of
      scientific uncertainty or misunderstanding, and differences in company approaches
      to enrollment in clinical trials. The survey also revealed that few companies
      collected data in a manner that would allow a retrospective understanding of the
      reasons for failure of birth control during clinical trials. In this article,
      suggestions are made for topics where regulatory guidance or scientific
      publications could facilitate best practice. These include provisions for a
      pragmatic definition of women of childbearing potential, guidance on how animal
      data can influence the requirements for male and female birth control, evidence
      based guidance on birth control and pregnancy testing regimes suitable for low-
      and high-risk situations, plus practical methods to ascertain the risk of drug
      drug interactions with hormonal contraceptives.

PMID- 27042399
TI  - Vascular Mimicry: The Next Big Glioblastoma Target.

PMID- 27042400
TI  - Mitotic bookmarking: maintaining post-mitotic reprogramming of transcription
      reactivation.
AB  - Restoring chromatin structure with high fidelity after mitosis is critical for
      cell survival. Transcriptional reactivation of genes is the first step toward
      establishing identity of the daughter cell. During mitosis, chromatin bookmarking
      factors associated with specific chromatin regions ensure the restoration of the
      original gene expression pattern in daughter cells. Recent findings have provided
      new insights into the mechanisms, regulation, and biological significance of gene
      bookmarking in eukaryotes. In this review, we discuss how epigenetic factors,
      such as Poly(ADP-ribose) Polymerase-1, establish epigenetic memory in mitotic
      chromatin.

PMID- 27042401
TI  - Identification of Plant Extracts that Inhibit the Formation of Diabetes-Linked
      IAPP Amyloid.
AB  - The extracts of 27 vegetables, spices and herbs were screened for their
      functional ability to inhibit the aggregation of islet amyloid polypeptide (IAPP,
      amylin) into toxic amyloid aggregates. The aggregation of IAPP has been directly
      linked to the death of pancreatic beta-islet cells in type 2 diabetes. Inhibiting
      the aggregation of IAPP is believed to have the potential to slow, if not prevent
      entirely, the progression of this disease. As vegetables, spices and herbs are
      known to possess many different positive health effects, the extracts of 27
      plants (abundant within the United States and spanning several plant families)
      were screened for their ability to inhibit the formation of toxic IAPP
      aggregates. Their anti-amyloid activities were assessed through (1) thioflavin T
      binding assays, (2) visualization of amyloid fibers using atomic force microscopy
      and (3) cell rescue studies. From this research, mint, peppermint, red bell
      pepper and thyme emerged as possessing the greatest anti-amyloid activity.

PMID- 27042402
TI  - How Fuzzy-Trace Theory Predicts True and False Memories for Words, Sentences, and
      Narratives.
AB  - Fuzzy-trace theory posits independent verbatim and gist memory processes, a
      distinction that has implications for such applied topics as eyewitness
      testimony. This distinction between precise, literal verbatim memory and meaning
      based, intuitive gist accounts for memory paradoxes including dissociations
      between true and false memory, false memories outlasting true memories, and
      developmental increases in false memory. We provide an overview of fuzzy-trace
      theory, and, using mathematical modeling, also present results demonstrating
      verbatim and gist memory in true and false recognition of narrative sentences and
      inferences. Results supported fuzzy-trace theory's dual-process view of memory:
      verbatim memory was relied on to reject meaning-consistent, but unpresented,
      sentences (via recollection rejection). However, verbatim memory was often not
      retrieved, and gist memory supported acceptance of these sentences (via
      similarity judgment and phantom recollection). Thus, mathematical models of words
      can be extended to explain memory for complex stimuli, such as narratives, the
      kind of memory interrogated in law.

PMID- 27042403
TI  - Ethnic Variations in Diabetes and Prediabetes Prevalence and the roles of Insulin
      Resistance and beta-cell Function: The CARRS and NHANES Studies.
AB  - AIMS: It is unclear how the prevalence of diabetes in Asian Indians in urban
      India compares to that of race/ethnic groups in the US that may have different
      underlying susceptibilities. Therefore we examined ethnic variations in the
      prevalence of type 2 diabetes, iIFG, iIGT, IFG+IGT, and the associated risk
      factors in Asian Indians in Chennai, India, and Whites, Blacks, and Hispanics in
      the United States. METHODS: Cross-sectional analyses, using representative
      samples of 4,867 Asian Indians aged 20-74 years from Chennai, India in the Centre
      for Cardiometabolic Risk Reduction in South-Asia study (CARRS) (2010-2011) and
      6,512 US Whites, Blacks, and Hispanics aged 20-74 years from the National Health
      and Nutrition Examination Survey (NHANES) (2007-2012). RESULTS: The age-adjusted
      prevalence of type 2 diabetes was highest in Asian Indians (men; 29.0, 95% CI:
      25.9, 31.0), women; (30.6, 95% CI, 27.5, 33.9)) and lowest in Caucasians (men;
      12.2, 95% CI, 10.3, 14.4), women; 9.5 (7.9, 11.5). Asian Indians had the lowest
      prediabetes prevalence (men; 19.0 (17.2, 20.8); women 27.2, 95% CI, 22.8, 32.1))
      and Caucasians had the highest (men; 46.5 (43.5, 49.6), women; 34.4, 95% CI,
      31.7, 37.3). However, there were differences in prediabetes prevalence by gender
      and prediabetes state. The inclusion of HOMA-beta in standardized polytomous
      logistic regression models resulted in a greater odds of diabetes in Blacks and
      Hispanics compared to Asian Indians. CONCLUSIONS: The high prevalence of diabetes
      in Asian Indians may be due to innate susceptibilities for beta-cell dysfunction
      in this high risk population.

PMID- 27042405
TI  - The Endocrine Society of India - A way forward.

PMID- 27042404
TI  - Contributions of neutrophils to the adaptive immune response in autoimmune
      disease.
AB  - Neutrophils are granulocytic cytotoxic leukocytes of the innate immune system
      that activate during acute inflammation. Neutrophils can also persist beyond the
      acute phase of inflammation to impact the adaptive immune response during chronic
      inflammation. In the context of the autoimmune disease, neutrophils modulating T
      and B cell functions by producing cytokines and chemokines, forming neutrophil
      extracellular traps, and acting as or priming antigen presentation cells. Thus,
      neutrophils are actively involved in chronic inflammation and tissue damage in
      autoimmune disease. Using rheumatoid arthritis as an example, this review focuses
      on functions of neutrophils in adaptive immunity and the therapeutic potential of
      these cells in the treatment of autoimmune disease and chronic inflammation.

PMID- 27042406
TI  - Of statins and low-density lipoprotein cholesterol, "fats" and fiction.

PMID- 27042407
TI  - Empagliflozin: Not just a glorified diuretic.

PMID- 27042408
TI  - Technetium uptake predicts remission and relapse in Grave's disease patients on
      antithyroid drugs for at least 1 year in South Indian subjects.
AB  - CONTEXT: Most of the information on remission related factors in Grave's disease
      are derived from Western literature. It is likely that there may be additional
      prognostic factors and differences in the postdrug treatment course of Grave's
      disease in India. AIM: To study factors which predict remission/relapse in
      Grave's disease patients from South India. Also to establish if technetium (Tc)
      uptake has a role in predicting remission. SUBJECTS AND METHODS: Records of 174
      patients with clinical, biochemical, and scintigraphic criteria consistent with
      Grave's disease, seen in our Institution between January 2006 and 2014 were
      analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical
      factors were compared between the remission and nonremission groups. STATISTICAL
      ANALYSIS USED: Mann-Whitney U-test and Chi-square tests were used when
      appropriate to compare the groups. RESULTS: Fifty-seven (32.7%) patients attained
      remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%)
      patients relapsed within 1 year. Age, gender, goiter, and presence of
      extrathyroidal manifestations were not associated with remission. Higher values
      of Tc uptake were positively associated with remission (P- 0.02). Time to
      achievement of normal thyroid function and composite dose: Time scores were
      significantly associated with remission (P - 0.05 and P - 0.01, respectively).
      Patients with lower FT4 at presentation had a higher chance of remission (P -
      0.01). The relapse rates were lower than previously reported in the literature. A
      higher Tc uptake was found to be significantly associated with relapse also (P -
      0.009). CONCLUSION: The prognostic factors associated with remission in Graves's
      disease in this South Indian study are not the same as that reported in Western
      literature. Tc scintigraphy may have an additional role in identifying people who
      are likely to undergo remission and thus predict the outcome of Grave's disease.

PMID- 27042409
TI  - Effect of steroid replacement on thyroid function and thyroid autoimmunity in
      Addison's disease with primary hypothyroidism.
AB  - BACKGROUND: Steroid replacement without thyroxine supplementation normalizes
      thyroid function test (TFT) in some but not all Addison's disease patients with
      primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute
      to this improvement in TFT. However, the documentation of the change in thyroid
      autoimmunity after cortisol replacement is very limited in the literature. The
      aim of this study was to determine the effect of steroid replacement on TFT and
      anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with
      primary hypothyroidism. MATERIALS AND METHODS: This observational study was
      conducted in a tertiary care center in South India. Six Addison's disease
      patients with primary hypothyroidism, who were only on steroid replacement, were
      included in the study. Low serum cortisol (<83 nmol/L) with high plasma
      adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous
      membranes was considered as the diagnostic criteria for Addison's disease.
      Primary hypothyroidism (both overt and subclinical) was defined as high thyroid
      stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO
      Ab were performed before and after steroid replacement in all of them. RESULTS:
      Poststeroid replacement, there was a normalization of TSH in all but one
      subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement
      in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six
      patients. However, there was a significant difference in TSH after steroid
      replacement compared to the baseline status. CONCLUSIONS: The concept of
      normalization of primary hypothyroidism with cortisol replacement in patients
      with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis
      caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms
      contribute to these alterations.

PMID- 27042410
TI  - Reference intervals in evaluation of maternal thyroid function of Manipuri women.
AB  - CONTEXT: The population of Manipur is of different ethnic background from the
      rest of the country. Several authors have suggested population/ethnic and
      laboratory specific reference range of maternal thyroid profile of different
      trimesters. AIMS: To find the reference range of thyroid stimulating hormone
      (TSH), total thyroxine (TT4) and total tri-iodothyronine (TT3) levels for normal
      pregnant women of native Manipur descendants. SETTINGS AND DESIGN: The cross
      sectional study was conducted at a teaching Institute after ethical clearance was
      obtained. SUBJECTS AND METHODS: A reference populations of 375 normal pregnant
      women were established after screening about 600 pregnant women. The study
      excluded patients with hyperemesis gravid arum, past history or family history of
      thyroid disorders as well as the connective tissue disorders, WHO grade 1 or 2
      goiter, or any medications that alter thyroid functions. The serum levels of TSH,
      TT4, and TT3 were measured using chemiluminescence assay. STATISTICAL ANALYSIS
      USED: Data for TT3 and TT4 were expressed as mean +/- standard deviation, median
      and 5-95(th) percentiles. RESULTS: The mean TSH in the three trimesters was 1.06
      + 0.45, 1.23 + 0.30, and 1.25 + 0.36, respectively. The normal reference range
      thus was different from that of the kit reference range. On comparing to the
      Indian normative reference for the pregnant women, our results were not similar.
      However, the values were near similar to that of the American Thyroid Association
      guidelines. CONCLUSIONS: We conclude our study results with a new reference range
      for the pregnant population in Manipur and also emphasis the use of trimester
      specific reference range of thyroid hormone.

PMID- 27042411
TI  - Iodine nutritional status in Uttarakhand State, India.
AB  - INTRODUCTION: Uttarakhand (UK) state is a known endemic region to iodine
      deficiency (ID). OBJECTIVE: To assess the current status of iodine nutrition in a
      population of UK. METHODOLOGY: Three districts, namely Udham Singh Nagar (USN),
      Nainital (N), and Pauri Garhwal (PG) were selected. In each district, 30 clusters
      were identified by utilizing the population proportional to size cluster sampling
      methodology. Total of 6143 school age children (SAC) (USN; 1807, N; 2269, PG:
      2067), 5430 adolescent girls (AGs) (USN; 1823, N; 1811, PG: 1796), 1727 pregnant
      mothers (PMs) (USN; 632, N; 614, PG: 481), and 2013 Neonates (USN; 649, N; 670,
      PG: 694), were included in the study. Clinical examination of thyroid of each
      child, AG and PM was conducted. Spot urine and salt samples were collected from
      children, AGs and PMs. Cord blood samples were collected from neonates for
      estimation of thyroid stimulating hormone (TSH). RESULTS: In SAC, total goiter
      rate (TGR) was 13.2% (USN), 15.9% (N), and 16.8% (PG). Median urinary iodine
      concentration (UIC) level was 150 MUg/l (USN), 125 MUg/l (N), and 115 MUg/l (PG).
      In AGs, TGR was 6.8% (USN), 8.2% (N) and 5.6% (PG). Median UIC level was 250
      MUg/l (USN), 200 MUg/l (N), and 183 MUg/l (PG). In PMs, TGR was 16.1% (USN),
      20.2% (N), and 24.9% (PG). Median UIC level was 124 MUg/l (USN), 117.5 MUg/l (N)
      and 110 MUg/l (PG), respectively. In Neonates, TSH levels of >5 mIU/L were found
      in 55.3 (USN), 76.4 (N) and 72.8 (PG) percent of neonates. CONCLUSION: UIC level
      in PMs and TSH levels among neonates indicate the prevalence of ID in three
      districts surveyed.

PMID- 27042412
TI  - Profile of leptin, adiponectin, and body fat in patients with hyperprolactinemia:
      Response to treatment with cabergoline.
AB  - INTRODUCTION: Though hypoadiponectinemia and leptin resistance have been proposed
      as potential factors for weight gain in patients with hyperprolactinemia (HPL),
      the effects of HPL and cabergoline on these adipocyte-derived hormones are not
      clear. Aims of this study were (i) to assess the alterations of body fat, leptin,
      and adiponectin in patients with HPL (ii) effect of cabergoline treatment on
      these parameters. METHODS: Nineteen consecutive patients with prolactinoma
      (median prolactin [PRL] 118.6 (interquartile range: 105.3) MUg/L) and 20 controls
      were studied in a nonrandomized matched prospective design. The controls were
      age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic
      variables, leptin, and adiponectin were studied at baseline and 3 and 6 months
      after cabergoline treatment. RESULTS: Patients with prolactinoma had increased
      level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI
      matched healthy controls. Estradiol concentration of controls was higher than
      that of patients (P = 0.018). Patients with prolactinoma had higher levels of
      leptin (P = 0.027) as compared to healthy controls without a significant
      difference in adiponectin levels. There was a significant decrease of body weight
      at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of
      cabergoline therapy. Furthermore, there was a significant decrement of BMI (P <
      0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body
      fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an
      increase in estradiol concentration (P = 0.03) at 6 months of cabergoline
      treatment. CONCLUSION: Patients with prolactinoma have adverse metabolic profile
      compared to matched controls. Normalization of PRL with cabergoline corrects all
      the metabolic abnormalities.

PMID- 27042413
TI  - Association between glycemic control and morning blood surge with vascular
      endothelial dysfunction in type 2 diabetes mellitus patients.
AB  - OBJECTIVE: Morning blood pressure surge (MBPS) is an independent predictor of
      cardiovascular events. However, little is known about the association between
      glycemic control and MBPS, and its effect on vascular injury in patients with
      type 2 diabetes mellitus (T2DM). The current study examined the association
      between glycemic control and MBPS and the involvement of MBPS in the development
      of vascular dysfunction in T2DM patients. MATERIALS AND METHODS: One hundred and
      twenty-two consecutive T2DM outpatients from the Department of Cardiology and
      Endocrinology were enrolled in this study. We did MBPS in T2DM patients, 85
      (male) (69.7%) patients and 37 (female) patients (30.3%); mean age 60.1 +/- 9.39;
      (n = 122) using 24 h ambulatory blood pressure monitoring and assessed vascular
      function by brachial artery flow-mediated dilation (FMD) and nitroglycerin
      mediated dilation (NMD). RESULTS: The correlation between MBPS and various
      clinical variables were examined by single regression analysis in all subjects.
      MBPS showed significant and positive correlation with pulse rate (P = 0.01),
      fasting blood sugar (P = 0.002), and postprandial blood sugar (P = 0.05). To
      further confirm the association of insulin resistance (IR) with MBPS in T2DM
      patients, we examined the correlation between homeostasis model assessment-IR
      (HOMA-IR), an established marker of IR and MBPS in diabetic (DM) patients who
      were not taking insulin no significant association with MBPS in T2DM patients (P
      = 0.41), angiotensin-converting enzyme/angiotensin receptor blocker (P = 0.07).
      We examined the relationship between MBPS and vascular injury by measuring
      endothelium-dependent FMD and endothelium-independent NMD in T2DM patients. Among
      the various traditional risk factors for atherosclerosis such as DM duration (P =
      0.04), platelet reactivity (P = 0.04) and morning surge (P = 0.002) emerged as
      significant factors. HOMA-IR was a negative correlation with FMD. CONCLUSIONS:
      The current study demonstrated that poor glycemic control and IR have predictive
      value for the occurrence of MBPS in T2DM patients, which might be significantly
      associated with endothelial dysfunction.

PMID- 27042414
TI  - Effect of Vitamin D supplementation on glycemic control in Type 2 diabetes
      subjects in Lagos, Nigeria.
AB  - INTRODUCTION: Improvement of glycemic control reduces the risk of diabetic
      complications. Reports suggest that Vitamin D supplementation improves glycemia.
      However, there are no data on the influence of Vitamin D on diabetes mellitus
      (DM) in Nigeria. OBJECTIVE: To determine the effect of Vitamin D supplementation
      on glycemic control in Type 2 DM (T2DM) participants with Vitamin D deficiency.
      DESIGN: This was a single-blind, prospective randomized placebo-controlled trial,
      involving T2DM participants attending the Diabetes Clinic of the Lagos University
      Teaching Hospital. Forty-two T2DM participants with poor glycemic control and
      Vitamin D deficiency were selected following a prior cross-sectional study on 114
      T2DM participants for the determination of Vitamin D status and glycemia. These
      participants were randomized into two equal groups of treatment and placebo arms.
      INTERVENTION: Three thousand IU of Vitamin D3 were given to the participants in
      the treatment arm. Glycemic status was determined at baseline and after 12 weeks.
      Statistical analysis was performed using Statistical Package for Social Sciences
      version 20. P < 0.05 was considered statistically significant. RESULTS: Vitamin
      D3 supplementation resulted in a significant improvement in serum Vitamin D level
      and fasting plasma glucose in the treatment arm compared to placebo. There was a
      nonsignificant reduction in the mean HbA1c level in the treatment group after 12
      weeks of Vitamin D3 supplementation (Z = -1.139; P = 0.127) compared to the
      placebo group, which had a further increase in the mean HbA1c level (Z = -1.424;
      P = 0.08). The proportion of participants with poor glycemic control (HbA1c >
      6.5%) who converted to good control after Vitamin D supplementation was
      significantly higher in the treatment arm compared to placebo (P < 0.05).
      CONCLUSION: Vitamin D3 supplementation in persons with T2DM and Vitamin D
      deficiency results in a significant improvement in glycemic control.

PMID- 27042415
TI  - Effects of gliclazide add on metformin on serum omentin-1 levels in patients with
      type 2 diabetes mellitus.
AB  - BACKGROUND: Omentin is a newly identified adipokine that has beneficial influence
      against cardiovascular disorders. Hence, considering the impact of anti-diabetic
      drug on omentin levels may provide an adjuvant strategy to protect diabetic
      patients against valuable clinical hazards. AIM OF THE STUDY: To investigate the
      influence of metformin alone or in combination with gliclazide on the level of
      serum omentin among patients with type 2 diabetes mellitus (T2DM). PATIENTS AND
      METHODS: A total of 70 newly diagnosed patients with T2DM were enrolled in this
      randomized, double-blind prospective study, and divided into two equal groups
      based on treatment regimen in which Group 1 treated with metformin (1000 mg) and
      Group 2 treated with metformin (1000 mg) plus gliclazide (80 mg). Blood glucose
      levels, HbA1C, insulin levels, and serum omentin-1 were measured at baseline and
      after 12 weeks of treatment. RESULT: Use of gliclazide as an add-on therapy to
      metformin in patients with T2DM result in better glycemic control evidenced by
      significant reductions in the levels of blood glucose levels and HbA1C and much
      more improvement in insulin sensitivity evidenced by significant decreased in
      insulin resistance index, whereas it has adverse impact on serum omentin-1 levels
      evidenced by significant decrement in omentin-1 level in comparison to their
      pretreatment levels among Group 2 patients. CONCLUSIONS: Adding of gliclazide to
      metformin in treatment of patients with T2DM might extend the therapeutic action
      of metformin in regarding much better controlling of glycemic indices, but, at
      the same time, it might attenuate the cardioprotective effects of metformin by
      its adverse influence on serum omentin-1 levels.

PMID- 27042416
TI  - Comatose and noncomatose adult diabetic ketoacidosis patients at the University
      Teaching Hospital, Zambia: Clinical profiles, risk factors, and mortality
      outcomes.
AB  - BACKGROUND: Diabetic ketoacidosis (DKA) is one of the commonly encountered
      diabetes mellitus emergencies. AIM: This study aimed at describing the clinical
      profiles and hospitalization outcomes of DKA patients at the University Teaching
      Hospital (UTH) in Lusaka, Zambia and to investigate the role of coma on mortality
      outcome. MATERIALS AND METHODS: This was a cross-sectional analytical study of
      hospitalized DKA patients at UTH. The data collected included clinical
      presentation, precipitating factors, laboratory profiles, complications, and
      hospitalization outcomes. Primary outcome measured was all-cause in-hospital
      mortality. RESULTS: The median age was 40 years. Treatment noncompliance was the
      single highest identified risk factor for development of DKA, followed by new
      detection of diabetes, then infections. Comatose patients were significantly
      younger, had lower baseline blood pressure readings, and higher baseline
      respiratory rates compared to noncomatose patients. In addition, comatose
      patients had higher baseline admission random blood glucose readings. Their
      baseline sodium and chloride levels were also higher. The prevalences of
      hypokalemia, hypernatremia, and hyperchloremia were also higher among comatose
      patients compared to noncomatose patients. Development of aspiration during
      admission with DKA, pneumonia at baseline, development of renal failure, and
      altered mental status were associated with an increased risk of mortality.
      Development of renal failure was independently predictive of mortality.
      CONCLUSION: The mortality rate from DKA hospitalizations is high at UTH.
      Treatment noncompliance is the single highest identifiable precipitant of DKA.
      Aspiration, development of renal failure, altered sensorium, and pneumonia at
      baseline are associated with an increased risk of mortality. Development of renal
      failure during admission is predictive of mortality.

PMID- 27042417
TI  - High prevalence of preobesity and obesity among medical students of Lahore and
      its relation with dietary habits and physical activity.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of obesity
      among students of medical colleges of Lahore and to study its correlation with
      high-caloric diet intake and physical inactivity. STUDY DESIGN: A cross-sectional
      survey was conducted at four medical colleges of Lahore, Pakistan between March
      and June 2012. METHODS: A total of 244 medical students (85 males, 159 females)
      of the median age of 20 years (range: 18-25) were randomly included in the study.
      Anthropometric measures were obtained. High-caloric diet intake and physical
      profile were assessed through a self-reported questionnaire. The relationships
      between obesity indices (body mass index [BMI], waist-to-hip ratio) were
      investigated and correlated with the studied dietary and physical activity
      factors. RESULTS: Approximately, 30.5% males and 16% females had BMI >=25.0
      kg/m(2) overall affecting 21% of total medical students. Central obesity was
      found in 46% of male and 31.4% of female students. Central obesity was associated
      with a higher total daily caloric intake, studying at private medical college and
      male gender. Overall, 197 of 244 (80.7%) students played no sports in college.
      Median time to watch television or work on the computer was 120 min a day (range:
      30-420). Only 70 (28.7%) students had regular walk or jogging. CONCLUSION: A
      substantial proportion of Pakistani medical students were overweight or obese.
      Higher total daily caloric intake was associated with central obesity but not a
      BMI >25. Physical activity parameters favored an overall sedentary aptitude for
      medical students.

PMID- 27042418
TI  - Gender differences in 7 years trends in cholesterol lipoproteins and lipids in
      India: Insights from a hospital database.
AB  - OBJECTIVE: To determine gender differences and secular trends in total, low
      density lipoprotein (LDL) and high DL (HDL) cholesterol and triglycerides using a
      large hospital database in India. METHODS: All blood lipid tests evaluated from
      July 2007 to December 2014 were analyzed. Details of gender and age were
      available. Statin therapy was obtained at two separate periods. Trends were
      calculated using linear regression and Mantel-Haenszel X(2). RESULTS: Data of
      67395 subjects (men 49,904, women 17,491) aged 51 +/- 12 years were analyzed.
      Mean levels (mg/dl) were total cholesterol 174.7 +/- 45, LDL cholesterol 110.7 +/
      38, non-HDL cholesterol 132.1 +/- 44.8, HDL cholesterol 44.1 +/- 10,
      triglycerides 140.8 +/- 99, and total: HDL cholesterol 4.44 +/- 1.5. Various
      dyslipidemias in men/women were total cholesterol >=200 mg/dl 25.4/36.4%, LDL
      cholesterol >=130 mg/dl 28.1/35.0% and >=100 mg/dl 54.4/66.4%, non-HDL
      cholesterol >=160 mg/dl 25.5/29.6%, HDL cholesterol <40/50 mg/dl 54.4/64.4%, and
      triglycerides >=150 mg/dl 34.0/26.8%. Cholesterol lipoproteins declined over 7
      years with greater decline in men versus women for cholesterol (Blinear
      regression = -0.82 vs. -0.33, LDL cholesterol (-1.01 vs. -0.65), non-HDL
      cholesterol (-0.88 vs. -0.52), and total: HDL cholesterol (-0.02 vs. -0.01). In
      men versus women there was greater decline in prevalence of hypercholesterolemia
      (X(2) trend 74.5 vs. 1.60), LDL cholesterol >=130 mg/dl (X(2) trend 415.5 vs.
      25.0) and >=100 mg/dl (X(2) trend 501.5 vs. 237.4), non-HDL cholesterol (X(2)
      trend 77.4 vs. 6.85), total: HDL cholesterol (X(2) trend 212.7 vs. 10.5) and high
      triglycerides (X(2) trend 10.8 vs. 6.15) (P < 0.01). Use of statins was in 2.6%
      (36/1405) in 2008 and 9.0% (228/2527) in 2014 (P < 0.01). Statin use was
      significantly lower in women (5.8%) than men (10.3%). CONCLUSIONS: In a large
      hospital - database we observed greater hypercholesterolemia and low HDL
      cholesterol in women. Mean levels and prevalence of high total, LDL, non-HDL and
      total: HDL cholesterol declined over 7 years. A lower decline was observed in
      women. This was associated with lower use of statins.

PMID- 27042419
TI  - DiabCare survey of diabetes management and complications in the Gulf countries.
AB  - AIM: To describe the status of diabetes control and complications, and the
      quality of diabetes management in Saudi Arabia, Kuwait, and the United Arab
      Emirates, and to obtain an insight into the relationship between these factors.
      METHODS: Patients with diabetes for>12 months were enrolled from specialist
      clinics and general hospitals. All available data from the patients' medical
      files including patient demographics; glycemic, lipid, and blood pressure status;
      diabetes-related complications; and diabetes management were recorded in data
      collection forms and analyzed. RESULTS: Overall, 1290 patients with diabetes were
      enrolled with a mean (+/-standard deviation) age of 49.4 +/- 12.3 years and
      duration of diabetes of 8.7 +/- 5.9 years. Glycemic control was poor: Mean
      glycated hemoglobin A1c of 8.3 +/- 2.0%, fasting and postprandial plasma glucose
      levels of 155.9 +/- 57.1 mg/dL (8.7 +/- 3.2 mmol/L), and 218.2 +/- 87.4 mg/dL
      (12.1 +/- 4.9 mmol/L), respectively. Diabetes-related complications such as
      neuropathy (34.9% of patients), background retinopathy (29.9%), and cataract
      (14.1%) were common. Cardiovascular complications were reported in <10% of
      patients, and microalbuminuria was detected in 34.4% of patients. Oral
      antidiabetic drug (OAD) monotherapy (43.3%) was the most common treatment,
      followed by insulin + OADs (39.3%) and insulin monotherapy (17.6%). CONCLUSION:
      The status of diabetes care was found to be suboptimal. Further improvements in
      diabetes management are necessary to prevent or delay the development of diabetes
      related complications.

PMID- 27042420
TI  - Prevalence of underweight, overweight, and obesity among 2, 162 Brazilian school
      adolescents.
AB  - INTRODUCTION: The nutritional profile of the Brazilian population has changed in
      recent years. Therefore, this study aimed to assess the prevalence of nutritional
      status among Brazilian school adolescents during the period from January 2014 to
      December 2014. METHODS: This study employed an observational design with a cohort
      of school adolescents. Anthropometric measurement was assessed by nutritionists
      in government schools. The cut-off points for body mass index according to
      Brazilian criteria for adolescents of both sexes between 10 years and 19 years
      old were underweight (<=17.5 kg/m(2)), overweigh (>=25.0 kg/m(2)), and obesity
      (>=30.0 kg/m(2)). RESULTS: The number of students included in the analysis was
      2162, of which 71.0% were males and 29% were females (P = 0.00001). The mean age
      (years) was 13.14 +/- 2.17 for boys and 12.66 +/- 1.85 for girls (P = 0.0001).
      The prevalence of underweight, overweight, and obesity observed in our population
      of school adolescents according to the Brazilian criteria was 2.8%, 8.1%, and
      2.4% for males, respectively, and 23.0%, 10.7%, and 3.6% for females,
      respectively. For both sexes, there was no statistically significant difference
      between overweight (P = 0.5469) and obesity (P = 0.7863), but there was for
      underweight (P = 0.001). CONCLUSIONS: The occurrence of excess weight among
      Brazilian school adolescents is similar to the international prevalence, but the
      prevalence of underweight was very high among girls. The nutritional status of
      adolescents must be considered a public health problem in Brazil.

PMID- 27042421
TI  - The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic
      patients of South Indian origin.
AB  - CONTEXT: Celiac disease (CD) is a commonly encountered autoimmune condition in
      patients with type 1 diabetes (T1D). There is sparse data on the seroprevalence
      of immunoglobulin A (IgA) transglutaminase (tTG) in T1D patients of South Indian
      origin. AIMS: To detect the prevalence of IgA tTG in T1D patients of South Indian
      origin. To evaluate the relation between the presence of autoimmunity and
      metabolic control and complications of diabetes. MATERIALS AND METHODS: We
      conducted a cross-sectional study on 258 T1D patients. All the patients were
      subjected to biochemical tests and evaluated for microvascular complications. IgA
      tTG was estimated by ELISA. IgA tTG levels >40 AU/ml was considered positive.
      RESULTS: Of the 258 participants, 12 (4.65%) were found to be positive for IgA
      tTG antibodies. Distribution of IgA positivity was equal in both sexes. There was
      a significant negative correlation of IgA tTG positivity with hemoglobin and
      glycated hemoglobin (HbA1c). CONCLUSIONS: The seropositivity of CD in South
      Indian patients with T1D has been observed to be 4.68%. This is much lower
      compared to studies from North India. This can be explained by both the genetic
      and dietary factors. The seropositivity correlated negatively with hemoglobin and
      HbA1c.

PMID- 27042422
TI  - Postural variation of pulmonary diffusing capacity as a marker of lung
      microangiopathy in Indian patients with type 2 diabetes mellitus.
AB  - INTRODUCTION: Diabetes mellitus (DM) is characterized by the presence of chronic
      hyperglycemia and formation of advanced glycation end products (AGEs).
      Interaction between AGE and its receptor leads to endothelial damage and
      microangiopathy. This study was undertaken to investigate the possibility of
      using a postural variation of diffusing capacity as an early marker of lung
      microangiopathy and its correlation with the level of adhesion molecules, HbA1c,
      duration of diabetes, and insulin resistance in type 2 DM (T2DM) patients with
      and without microangiopathy. MATERIALS AND METHODS: Forty patients having T2DM
      without any microangiopathy (n = 20) as well as with microangiopathy (n = 20),
      and 22 age and sex matched healthy controls were enrolled in this cross-sectional
      study. Measurement of lung volumes and capacities were done. DLco was measured in
      sitting and supine position. Levels of vascular cell adhesion molecule-1 (VCAM
      1), E-selectin, fasting glucose, and insulin were estimated in plasma of the
      patients and compared with controls. RESULTS: Restrictive type of ventilatory
      change was observed in DM patients. Diffusing capacity (% predicted) in the
      supine position (P < 0.0001), postural change in DLco (P < 0.0001), and
      coefficient of diffusion were significantly less in DM patients as compared to
      controls. Plasma levels of VCAM-1 were significantly higher in DM patients
      without microangiopathy and negatively correlated (r = -0.4054, P = 0.0094) with
      Delta DLco in all diabetic subjects. All patients had significantly higher
      insulin resistance. CONCLUSION: Lack of postural increase in diffusing capacity
      in type 2 diabetic patients along with increased VCAM-1 levels could reflect the
      presence of an early microangiopathy of the small pulmonary vessels.

PMID- 27042423
TI  - Sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors
      combination therapy in type 2 diabetes: A systematic review of current evidence.
AB  - As type 2 diabetes mellitus (T2DM) is a chronic and progressive disease with
      multiple pathophysiologic defects, no single anti-diabetic agent can tackle all
      these multi-factorial pathways. Consequently, multiple agents working through the
      different mechanisms will be required for the optimal glycemic control. Moreover,
      the combination therapies of different anti-diabetic agents may complement their
      actions and possibly act synergistic. Furthermore, these combinations could
      possess the additional properties to counter their undesired physiological
      compensatory response. Sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are
      newly emerging class of drugs, with a great potential to reduce glucose
      effectively with an additional quality of lowering cardiovascular events as
      demonstrated very recently by one of the agents of this class. However, increase
      in endogenous glucose production (EGP) from the liver, either due to the increase
      in glucagon or compensatory response to glucosuria can offset the glucose
      lowering potential of SGLT-2I. Interestingly, another class of drugs such as
      dipeptidyl peptidase-4 inhibitors (DPP-4I) effectively decrease glucagon and
      reduce EGP. In light of these findings, combination therapies with SGLT-2I and
      DPP-4I are particularly appealing and are expected to produce a synergistic
      effect. Preclinical studies of combination therapies with DPP-4I and SGLT-2I have
      already demonstrated a significant lowering of hemoglobin A1c potential and human
      studies also find no drug-drug interaction between these agents. This article
      aims to systematically review the efficacy and safety of combination therapy of
      SGLT-2I and DPP-4I in T2DM. 

PMID- 27042424
TI  - Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes:
      Past, present, and future.
AB  - Glucagon-like peptide-1 (GLP-1)-based therapy improves glycaemic control through
      multiple mechanisms, with a low risk of hypoglycaemia and the additional benefit
      of clinically relevant weight loss. Since Starling and Bayliss first proposed the
      existence of intestinal secretions that stimulate the pancreas, tremendous
      progress has been made in the area of incretins. As a number of GLP-1 receptor
      agonists (GLP-1 RAs) continue to become available, physicians will soon face the
      challenge of selecting the right option customized to their patient's needs. The
      following discussion, derived from an extensive literature search using the
      PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide,
      albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide, provides a
      comprehensive review of existing and upcoming molecules in the GLP-1 RA class in
      terms of their structure, pharmacological profiles, efficacy, safety, and
      convenience. Search Methodology: A literature search was conducted using the
      PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide,
      albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide. Relevant
      articles were those that discussed structural, pharmacokinetic and
      pharmacodynamic differences, classification, long-acting and short-acting GLP-1
      RAs, phase 3 trials, and expert opinions. Additional targeted searches were
      conducted on diabetes treatment guidelines and reviews on safety, as well as the
      American Diabetes Association/European Society for Study of Diabetes (ADA/EASD)
      statement on pancreatic safety. 

PMID- 27042426
TI  - Proceedings of the EIP on AHA: A3 Action Group on Frailty.

PMID- 27042425
TI  - Management of anemia in patients with diabetic kidney disease: A consensus
      statement.
AB  - This consensus statement focuses on the window of opportunity, which exists while
      treating patients with diabetic kidney disease and anemia. 

PMID- 27042428
TI  - Nutrition and Osteoporosis: Preliminary data of Campania Region of European
      PERsonalised ICT Supported Service for Independent Living and Active Ageing.
AB  - BACKGROUND: Bone impairment and malnutrition are associated with significant
      disability and mortality. PERSSILAA is an European project developing health
      services to detect and prevent frailty in older adults by addressing cognitive,
      physical and nutritional. METHODS: Subjects underwent anthropometric
      measurements, calcaneal quantitative ultrasound (QUS) scan and PREDIMED
      (PREvencion con DIeta MEDiterranea) questionnaire. AIM: To investigate the
      association between adherence to the Mediterranean Diet (MD) and bone health.
      RESULTS: 87 subjects (4 males and 83 females) 70.1+/-4.9 aged, were examined.
      Mean Body Mass Index (BMI) was 28.7+/-4.7(kg/m(2)): in particular 28 subjects
      (32.2%) resulted obese, 42 (48.3%) overweight, and only 17 (19.5%) with normal
      weight. Mean T score was -1.2+/-1.2: in particular 13 subjects (14.9%) resulted
      osteoporotic; 43 (49.5%) osteopenic; and 31 (35.6%) with normal bone mineral
      density. Regarding adherence to MD, 9 subjects (10.3%) were poorly adherent; 41
      (47.2%) average adherent; 37 (42.5%) highly adherent. T-score was associated with
      PREDIMED score and osteoporotic subjects presented the lowest PREDIMED score
      (5.8+/-2.2). CONCLUSIONS: These preliminary data show a significant correlation
      between the adherence to the MD and bone health parameters. The association
      between MD and bone health highlights the potential beneficial effects of
      nutritional interventions promoting a Mediterranean food pattern, as safe
      adjuvant treatment in ageing.

PMID- 27042427
TI  - Models for preclinical studies in aging-related disorders: One is not for all.
AB  - Preclinical studies are essentially based on animal models of a particular
      disease. The primary purpose of preclinical efficacy studies is to support
      generalization of treatment-effect relationships to human subjects. Researchers
      aim to demonstrate a causal relationship between an investigational agent and a
      disease-related phenotype in such models. Numerous factors can muddle reliable
      inferences about such cause-effect relationships, including biased outcome
      assessment due to experimenter expectations. For instance, responses in a
      particular inbred mouse might be specific to the strain, limiting
      generalizability. Selecting well-justified and widely acknowledged model systems
      represents the best start in designing preclinical studies, especially to
      overcome any potential bias related to the model itself. This is particularly
      true in the research that focuses on aging, which carries unique challenges,
      mainly attributable to the fact that our already long lifespan makes designing
      experiments that use people as subjects extremely difficult and largely
      impractical. 

PMID- 27042429
TI  - Rest Rust ! Physical active for active and healthy ageing.
AB  - The aim of this paper is to give an insight on how physical activity can be
      defined, parameterized and measured in older adults and on different options to
      deal with citizen physical activity promotion at European level. Three relevant
      aspects are highlighted: When talking about physical activity, two different
      aspects are often unfairly mixed up: "physical activity" and "physical capacity".
      Physical activity, is referred to as the level of physical activity someone is
      actually performing in daily life.Physical capacity is referred to as the maximum
      physical activity a person can perform.Both physical activity and physical
      capacity can be expressed in different dimensions such as time, frequency, or
      type of activity with the consequence that there are many tools and techniques
      available. In order to support people to choose an appropriate instrument in
      their everyday practice a list of 9 criteria that are considered important is
      defined.Older adults score differently across the various physical dimensions, so
      strategies to promote physical activity should consider individual differences,
      in order to adapt for these variations. 

PMID- 27042430
TI  - Operationalization of the physical frailty & sarcopenia syndrome: rationale and
      clinical implementation.
AB  - Over the years, different operational definitions have been elaborated to
      identify frail older persons, but none of them has received unanimous consensus.
      This, in turn, has hampered the clinical implementation of frailty as well as the
      design of targeted interventions. To overcome the current limitations in the
      field, a novel operationalization of physical frailty (PF) is proposed which
      grounds its roots in the recognition of sarcopenia as its central biological
      substrate. This conceptualization is based on the fact that the clinical picture
      of PF overlaps substantially with that of sarcopenia. The two conditions may
      therefore be merged into a new clinical entity, the PF & sarcopenia (PF&S)
      syndrome, in which muscle loss represents both the biological substrate for the
      development of PF and a major pathway whereby the negative health outcomes of PF
      occur. All of the components defining the PF&S syndrome are measurable in an
      objective manner, which will facilitate its incorporation into standard practice.
      The recognition of a precise biological substratum for PF&S (i.e., skeletal
      muscle decline) also opens new venues for the development of preventive and
      therapeutic interventions. 

PMID- 27042431
TI  - A Nutritional Approach to the Prevention of Cancer: from Assessment to
      Personalized Intervention.
AB  - Among lifestyle factors, nutrition is one of the most important determinants of
      health, and represents a pivotal element of cancer risk. Nonetheless,
      epidemiological evidences of the relationship between several cancers and
      specific foods and nutrients is still inadequate, and solid conclusions are
      missing. Indeed, caloric restriction without malnutrition is associated to cancer
      prevention. Food may be also the primary route of exposure to contaminants such
      as metals, persistent organic pollutants, and pesticides. Exposuredisease
      associations and the interplay with genetic susceptibility requires further
      studies on genetic variation, environment, lifestyle, and chronic disease in
      order to eliminate and reduce associated health risks, thus contributing to
      improve health outcomes for the population. A primary nutritional approach for
      Active and Healthy Ageing (AHA) has been developed by the Nutrition group of the
      European Innovation Partnership (EIP) on AHA. The working group on lifestyles of
      the Italian Ministry of Health has developed a comprehensive approach to adequate
      nutrition using a consensus methodology to collect and integrate the available
      evidences from the literature and from the Italian experiences at the regional
      level, to raise the interest of other experts and relevant stakeholders to
      outline and scale-up joint strategies for a primary nutritional approach to
      cancer prevention. 

PMID- 27042432
TI  - The Role Of Physical Activity On The Prevention Of Cognitive Impairment.
AB  - Physical exercise is associated with reduced risk of heart disease, type II
      diabetes mellitus, and overall mortality. However, growing evidence shows that
      physical activity can also improve cognitive function and may lower the risk of
      developing dementia, but Randomized Clinical Trials gave mixed results. Aim of
      this article was to review the knowledge available in literature on the effects
      of physical activity on cognition and the suggested possible mechanisms involved
      in these effects. Our group have planned a trial aiming to evaluate the
      effectiveness of physical activity in preventing or delaying the cognitive
      decline in individuals at risk of developing dementia. Beside the effects of
      exercise on cognition are not fully defined, also the mechanisms underlying the
      benefits of physical activity on cognitive sphere are not completely known.
      Recently the SIRT1 loss is both closely associated with accumulation of beta
      amyloid and tau protein in AD patients. Although there is no specific exercise
      that can be recommended, the available evidence suggests that practicing more
      types of physical activity is particularly advantageous. It is important to
      explore further mechanisms involved in the pathogenesis of the AD in order to be
      able to identify new and effective target treatment, including physical activity.

PMID- 27042433
TI  - Effects of Resveratrol on p66Shc phosphorylation in cultured prostate cells.
AB  - There is increasing evidence that diet plays a crucial role in age-related
      diseases and cancer. Oxidative stress is a conceivable link between diet and
      diseases, thus food antioxidants, counteracting the damage caused by oxidation,
      are potential tools for fight age-related diseases and cancer. Resveratrol (RSV),
      a polyphenolic antioxidant from grapes, has gained enormous attention
      particularly because of its ability to induce growth arrest and apoptosis in
      cancer cells, and it has been proposed as both chemopreventive and therapeutic
      agent for cancer and other diseases. Even though the effects of RSV have been
      studied in prostate cancer cells and animal models, little is known about its
      effects on normal cells and tissues. To address this issue, we have investigated
      the effects of RSV on EPN cells, a human non-transformed prostate cell line,
      focusing on the relationship between RSV and p66Shc, a redox enzyme whose
      activities strikingly intersect those of RSV. p66Shc activity is regulated by
      phosphorylation of serine 36 (Ser36) and has been related to mitochondrial
      oxidative stress, apoptosis induction, regulation of cell proliferation and
      migration. Here we show that RSV inhibits adhesion, proliferation and migration
      of EPN cells, and that these effects are associated to induction of dose- and
      time-dependent p66Shc-Ser36 phosphorylation and ERK1/2 de-phosphorylation.
      Moreover, we found that RSV is able to activate also p52Shc, another member of
      the Shc protein family. These data show that RSV affects non-transformed prostate
      epithelial cells and suggest that Shc proteins may be key contributors of RSV
      effects on prostate cells. 

PMID- 27042434
TI  - How healthy is community-dwelling elderly population? Results from Southern
      Italy.
AB  - PURPOSE: To explore the frequency of polypharmacy, functional and cognitive
      capacity among the elderly in Southern Italy. METHODS: Population-based
      retrospective cross-sectional study. Information were retrieved from electronic
      geriatric-forms matched by record-linkage to outpatient pharmacy-records. The
      following domains were collected from geriatric forms: BMI, cognitive capacity
      (SPMSQ), functional status (Barthel-index), mobility, living condition.
      Polypharmacy status was categorized as non-polypharmacy (0-4), polypharmacy (5-9)
      and excessive-polypharmacy (>=10). Prevalence of all variables were stratified by
      age and polypharmacy group. RESULTS: 88,878 old people received a geriatric
      assessment in the years 2013-2014. Mean age was 74.8 (+/-7.3) years, 56.6%
      females. Proportion of elderly in excessive-polypharmacy increased with age
      (18.9% in 65-75 age-group; 27.9% in >85). Referring to cognitive capacity, the
      proportion of lucid patients decreased with age (from 94.3% to 58.1%), while
      confused patient increased with age (from 4.7% to 30.9%). Proportion of subjects
      with a decline in cognitive status, functional status and mobility increased in
      polypharmacy and excessive polypharmacy group. CONCLUSION: Polypharmacy is common
      in people aged 65 years and older with difficulties in activities of daily living
      and impaired cognition. Furthermore, its prevalence raises with increasing age.
      Preventive strategies such us optimization of drug regimen should be performed
      routinely to reduce risk of adverse-health-events.

PMID- 27042435
TI  - Errata Corrige: "What the Young Physician Should know About May-Thurner Syndrome"
      Transl Med Unisa. 2014 Sep 1;12:19-28.
AB  - [This corrects the article on p. 19 in vol. 12, PMID: 26535184.]. 

PMID- 27042436
TI  - Analysis of the Distribution of Mucins in Adult Human Gastric Mucosa and Its
      Functional Significance.
AB  - INTRODUCTION: Mucins are complex composition of carbohydrates seen in the
      epithelial cells lining the gastrointestinal tract (GIT). Normal distribution of
      such mucins in different part of the GIT and its alteration in various
      inflammatory, benign and malignant lesions of GIT has aroused interest in the
      field of histochemistry. AIM: By applying variety of histochemical techniques an
      attempt has been made to draw a map of mucin secretion by the different
      epithelial cell types in different parts of the stomach. MATERIALS AND METHODS:
      Fifty samples were taken each from different parts of the stomach like fundus,
      body and pylorus, from dissected fresh specimens (total of 150 specimens). Tissue
      samples were subjected for routine process and studied for histological and
      different histochemical staining. RESULTS: Mucin pattern in adult predominantly
      secretes neutral mucosubstances. Surface epithelium shows predominant neutral
      mucin while cardiac and gastric glands with foveolar cells show moderate amount.
      Sialomucin is present in a few cells of the surface epithelium, foveolar cells
      and in most of the mucous neck cells. Small amount of sialomucin and sulphomucin
      are found in surface epithelial foveolar cells while traces of sulphomucin are
      found in deep foveolar cells. Mucous neck cells secrete both sulphomucin and
      sialomucin. CONCLUSION: Normal gastric mucosa adjacent to gastric ulcers and
      malignant tumours of stomach secretes mucins which differ histochemically and
      biochemically from that of normal. Early recognition of such changes could be
      useful in recognizing the different type of carcinomas and their prognosis.

PMID- 27042437
TI  - A Study of the Supratrochlear Foramen of the Humerus: Anatomical and Clinical
      Perspective.
AB  - INTRODUCTION: The Supratrochlear Foramen (STF) is a variably shaped perforation
      present in the bony septum that separates the olecranon and coronoid fossae at
      the distal end of the humerus, between the two epicondyles. Its incidence varies
      widely from 0.3% to 58% in different races. AIM: This study aims to describe its
      prevalence and morphometry in relation to its shape and size and distance from
      the epicondyles. MATERIALS AND METHODS: A prospective study of 244 unpaired
      humerii, 130 of the left side and 114 of the right side of unknown age and sex
      were examined for the presence of STF and prevalence stated. The STF was
      classified according to shape and their metric assessment was carried out, along
      with measures of its distance from the epicodyles and trochlear margin. RESULTS:
      Of the 244 humeri studied 60 showed presence of the foramen, 45 were opaque and
      139 showed translucent septum. The sidewise prevalence of opacity, translucent
      septum and foraminae were tabulated. The commonest shape noted was oval. Other
      shapes such as round, triangular, rectangular, sieve and reniform were
      visualised. In the oval STF, transverse and vertical diameters were measured. The
      transverse and vertical diameters on the left were 4.9 and 3.27 mm and on the
      right it was 5.12 and 3.48mm respectively. The distance from the medial
      epicondyle, lateral epicondyle and trochlea to the STF margins was measured and
      the mean values were calculated separately for right and left sides. The mean
      diameter of the round foramen was 3.23 and 4.89mm for left and right sides
      respectively. In the triangular type the maximum vertical and transverse
      diameters were recorded. There was only one sample of the rectangular type. Its
      length was 4.1mm and the breadth was 2.27mm and it belonged to the right side.
      The reniform type totalled 7 of which 6 were of the left side. The average
      vertical length at the hilum was 4.52 mm and the transverse measurement was 7.44
      mm. The foraminae of the right side were found to be larger, regardless of shape.
      CONCLUSION: Its existence is important to the orthopaedician in the preoperative
      planning of nailing fractures of the distal humerus and to the radiologist for
      differentiating it from an osteolytic or cystic lesion.

PMID- 27042438
TI  - Martin-Gruber Anastomosis- A Cadaveric Study in North Indian Population.
AB  - INTRODUCTION: Communications between peripheral nerves are important in the light
      of the fact that these are responsible for a myriad of clinical symptoms.
      Communication between the median nerve and ulnar nerve (Martin-Gruber
      anastomosis) is a frequent finding observed anatomically in 10%-30.6% subjects
      and physiologically in 5-40%. It may lead to exacerbated or attenuated clinical
      symptoms. AIMS & OBJECTIVES: To find out the incidence of Martin-Gruber
      anastomosis in North Indian population by cadaveric dissection. MATERIALS AND
      METHODS: The material comprised of 60 upper limbs belonging to 30 cadavers
      (M:F::28:2) which were dissected to find out incidence of Martin-Gruber
      anastomosis. RESULTS: Martin-Gruber anastomosis was encountered in 7(11.6%) limbs
      of the present study. It was seen more frequently unilaterally (16.6%) than
      bilaterally (3.3%) and only in males. Classification of limbs into various
      patterns and types was done. Further its ontogeny, phylogeny, genetic inheritance
      and clinical implications are discussed in detail. CONCLUSION: To conclude, in
      North Indian population, the Martin-Gruber anastomosis is encountered in 11.6%
      limbs.

PMID- 27042439
TI  - Anatomical Consideration and Potential Complications of Coronary Sinus
      Catheterisation.
AB  - INTRODUCTION: Coronary venous catheterisation has been used for performing
      various cardiologic interventions. The procedure might become complicated due to
      obstruction offered by the valve of coronary sinus (Thebesian valve) the acute
      bend of the Great Cardiac Vein (GCV). The present study sought to expound the
      anatomical considerations of coronary venous catheterization and to elucidate the
      potential causes of obstruction and the complications of this procedure.
      MATERIALS AND METHODS: In this cross-sectional observational study, coronary
      sinus and GCV were dissected in 40, formalin fixed, adult cadaveric human hearts.
      Course, length, diameter and angle of bend of GCV, length of coronary sinus and
      its diameter at its ostium in right atrium were recorded. Thebesian valve
      morphology and percentage coverage of coronary sinus ostium was recorded.
      Relation of the coronary sinus and GCV with their neighbouring arteries was
      described. RESULTS: Coronary sinus: near its termination was directly related to
      the left atrium. Length: 35.35+/-4.43 mm (1 SD). Diameter: 11.75 +/- 2.66mm.
      Diameter of CS ostium was more in hearts where Thebesian valve was absent. GCV
      travelled superficial or deep to the left diagonal artery and crossed circumflex
      artery superficially. Length: 96.23 +/-22.52mm. Diameter: 5.99 +/-1.02mm. Angle
      of bend: 107 +/-6.74 degrees. Thebesian valve: Absent in 3 hearts. Various
      morphologies were observed: thin band, thin band with fenestrations, broad band
      with fenestrations, well developed semilunar valve (Thin/thick). In five hearts,
      valve covered more than 50% of coronary sinus ostium. CONCLUSION: Coronary sinus
      and GCV diameter will help cardiologists and cardiothoracic surgeons to choose an
      appropriate sized catheter and their length will decide the length of catheter
      advancement. Thebesian valve may cause obstruction to the catheter due to an
      extensive coverage of coronary sinus ostium, which is seen in 12.5% cases. The
      obtuse angle of GCV has to be negotiated in order to enter this vessel. Arteries
      lying deep to coronary sinus and GCV might be compressed leading to myocardial
      ischemia.

PMID- 27042440
TI  - Bifurcated Bicipital Aponeurosis Giving Origin to Flexor and Extensor Muscles of
      the Forearm - A Case Report.
AB  - Bicipital aponeurosis is usually attached to the antebrachial fascia on the
      medial side of forearm and to posterior border of ulna assisting in the
      supination of the forearm along with biceps brachii muscle. Variations in the
      bicipital aponeurosis may lead to neurovascular compression as reported earlier.
      In the present case, the bicipital aponeurosis had two slips i.e. medial and
      lateral. Medial slip gave origin to some fibers of pronator teres and flexor
      carpi radialis and the lateral slip gave origin to some fibers of
      brachioradialis. Such unusual slips of bicipital aponeurosis may distribute the
      stress concentration and may work in different directions affecting the
      supination of forearm by biceps brachii muscle and bicipital aponeurosis. 

PMID- 27042441
TI  - The Extensor Indicis Brevis - A Rare Variation and its Significance.
AB  - Variations in muscle attachments are valuable in interpreting rare clinical
      conditions. This case report discusses about the abnormal extensor indicis muscle
      attachment in left hand of male cadaver and its clinical relevance. The extensor
      indicis muscle was arising from lunate carpal bone and posterior radiocarpal
      ligament which further continued as short belly and had its distal attachment on
      the proximal phalanx of the index finger. This muscular variation has been
      described in earlier studies with 1.0% incidence. Abnormal origin of extensor
      indicis may be associated with pain and swelling at the back of the hand. This
      pain may be confused with other clinical conditions like synovial cyst and
      ganglion. Knowledge of such rare variations are useful to clinicians, surgeons,
      occupational and physical therapists for planning better surgical decisions. 

PMID- 27042442
TI  - Comparative Study of 5'-Nucleotidase Test in Various Liver Diseases.
AB  - INTRODUCTION: The liver regulates many important metabolic functions. The 5'
      nucleotidase activity is increased in obstructive jaundice, parenchymal liver
      disease, and hepatic metastases. AIM: This study was conducted to assess the
      serum levels of 5'-nucleotidase on patients with viral hepatitis, alcoholic liver
      diseases and liver cirrhosis, moreover to make comparison to assess the degree of
      biliary involvement. MATERIALS AND METHODS: A total of 60 male subjects (15
      healthy controls and 45 case subjects) were enrolled, aged between 30 -50 years,
      each case group consisted of 15 male age-matched patients suffering with viral
      hepatitis, alcoholic liver disease (more than 10 years.) and liver cirrhosis.
      Serum 5'-nucleotidase was analyzed as per the standard laboratory procedure.
      RESULTS: The 5'-nucleotidase levels were significantly raised in viral hepatitis,
      alcoholic liver disease and cirrhosis patients. The levels being 35.2+/-8.43,
      29.87+/-3.94, and 24.07+/- 4.33 respectively as compared to healthy control (11+/
      3.42) U/L. CONCLUSION: Serum 5'-nucleotidase levels showed elevations in mean
      value of three fold in viral hepatitis, 2.5 folds elevation in alcoholic liver
      disease and two fold in cirrhosis as compared of healthy control subjects.

PMID- 27042443
TI  - Lipid Peroxidation and Antioxidant Status in Patients with Medullary Thyroid
      Carcinoma: A Case-Control Study.
AB  - INTRODUCTION: Oxidative stress or oxidant/antioxidant imbalance has a crucial
      role in the pathogenesis of some diseases like cancer. Medullary thyroid
      carcinoma (MTC) originates in the thyroid parafollicular cells and includes 3-4%
      of the malignant neoplasms that have an effect on this gland. The aetiology of
      MTC has not been clarified. However, oxidative stress may be one of the factors
      involved. AIM: The aim of the current study was to evaluate the antioxidant
      enzyme activity of catalase (CAT), Glutathione (GSH), total antioxidant capacity
      (TAC) and the levels of the lipid peroxidation product malondialdehyde (MDA) in
      blood samples of MTC patients as compared to healthy controls. MATERIALS AND
      METHODS: A case-control study was designed enrolling patients with confirmed MTC
      diagnosis and age-and sex group matched healthy volunteers referred to the clinic
      of the Research Institute for Endocrine Sciences, Tehran, Iran from April 2013 to
      July 2015. Fasting blood samples were taken for study. Catalase, GSH, MDA and TAC
      levels were measured by colorimetry using commercial kits (ZellBio GmbH,
      Germany). Data were analysed using SPSS 17 software, comparing mean+/-SD through
      t-test and difference between proportions through chi-square. RESULTS: No
      statistical difference was observed in the demographic characteristic between
      cases and controls. The final MTC group included 40 males and 45 females with a
      mean age of 30+/-12.9 year, and the control group 40 males and 47 females, with a
      mean age of 31.2+/-12.3 year. Anthropometric parameters, dietary and thyroid
      hormones levels (T3, T4 and TSH) were similar. Serum TAC (p=0.015), GSH (p=0.029)
      and CAT (p<0.001) levels were found to be significantly lower in the MTC
      patients, while serum MDA levels were significantly higher in MTC patients than
      controls (p<0.001). CONCLUSION: These preliminary findings suggest that
      oxidant/antioxidant imbalance may be associated with or possibly indicate an
      increased risk to medullary thyroid carcinoma. Further studies are needed to
      explore these findings.

PMID- 27042444
TI  - Correlation of Oxidative Damage with Pro-Inflammatory Markers (IL-6, TNF-alpha)
      in Meningocele.
AB  - INTRODUCTION: Oxidative damage induces alteration in the status of pro
      inflammatory markers like IL-6 and TNF-alpha in meningocele. The study was
      performed with estimation of the levels of MDA (Malonyldialdehyde), SOD
      (Superoxide dismutase) taken as oxidative damage markers and IL-6 (interleukin 6)
      and TNF-alpha (Tumour necrosis factor alpha) taken as inflammatory markers, in
      the serum of meningocele patients and age, sex matched normal neonates.
      Correlation among the different serum levels of MDA, SOD, IL-6 and TNF-alpha was
      determined. MATERIALS AND METHODS: It is a case-control study, comprising of 153
      participants: 101 newborns with meningocele and 52 healthy newborns. The study
      was conducted in the Department of Biochemistry, Institute of Medical Sciences,
      Banaras Hindu University, Varanasi, in collaboration with the Department of
      Paediatric Surgery and Department of Obstetrics and Gynecology, Sir Sunderlal
      Hospital, Banaras Hindu University, Varanasi. The study was conducted during the
      period of 2012 to 2014. Serum was extracted from blood collected from both groups
      i.e. meningocele patient group and healthy neonatal control group. The levels of
      MDA and SOD were determined by spectrophotometric method. IL-6 was determined by
      the Human IL-6 High Sensitivity ELISA Kit and TNF-alpha was determined by the
      Human TNF-alpha ELISA KIT. RESULTS: The levels of MDA, TNF-alpha and IL-6 were
      found to be much higher and level of SOD was found lower in the patients with
      meningocele as compared to the normal healthy neonates. CONCLUSION: Increased MDA
      (oxidative damage product), IL-6, and TNF-alpha (inflammatory marker) and low
      level of SOD shows an increased inflammatory response in Meningocele. Our study
      shows Negative Correlation between MDA and SOD in case & control groups, while a
      Positive Correlation between TNF alpha and IL-6 in control & case groups.

PMID- 27042445
TI  - Insulin-Like Growth Factor I Receptor (IGF-IR) Ligands and BMI in Squamous Intra
      Epithelial Lesion (SIL) of Cervix.
AB  - INTRODUCTION: Cancer cervix is the most common cancer in women in developing
      countries like India. Several studies have linked insulin-like growth factors-I &
      II (IGF-I and IGF-II) and IGF binding proteins-3 (IGFBP-3) with pathogenesis of
      Squamous Intraepithelial Lesion of cervix (SIL). To the best of our knowledge, no
      study has shown any correlation between circulating C-Peptide levels and SIL.
      AIM: The present study has attempted to evaluate the correlation between SIL and
      IGF-IR ligands (IGF-I, IGF-II, C-Peptide), IGF binding protein (IGFBP-3) and Body
      Mass Index (BMI). MATERIALS AND METHODS: The present case-control study consisted
      of 31 histologically proven SIL cases and 31 age matched controls without
      evidence of SIL. A 10 ml blood sample was collected in heparinized vial. Plasma
      was separated immediately using centrifugation and was stored at -80(0) C till
      further analysis. Plasma levels of IGF-I, IGF-II, C-peptide and IGFBP3 were
      measured using commercially available Enzyme Linked Immunosorbent Assay (ELISA)
      kit. Height and weight was noted for calculation of BMI. Bio-effective molar
      ratio (BEMR) was calculated as 3.72 x {(0.25 x IGF-I) + (0.032 x IGF-II) +
      (0.0025 x C-peptide)} / {(1435 + IGFBP-3) - (2.79 x IGF-I) - (2.87 x IGF-II)}.
      Statistical analysis was performed using SPSS and Microsoft Excel software
      employing student t-test, Mann-Whitney and Chi-square test for trend while binary
      logistic regression was used to estimate the odds ratios (OR) and corresponding
      95% Confidence Intervals (CI). RESULT: IGF-I, IGF-II levels and BEMR were
      significantly increased in SIL compared to controls (p= 0.001, p <0.001, and p
      <0.001, respectively). C-Peptide levels were higher in controls than SIL (p =
      0.04). IGFBP-3 & BMI in SIL were not significantly related when compared with
      controls. Risk of SIL in 4(th) quartile for BEMR, IGF-I, and IGF-II was 12.18(95%
      CI= 3.13-47.39), 3.94(95% CI = 1.24-12.56), and 4.57(95% CI = 1.42-14.7),
      respectively. CONCLUSION: Elevated levels of IGF-I and IGF-II are associated with
      risk of SIL while BEMR emerges out to be a derived factor strongly associated
      with risk of SIL.

PMID- 27042446
TI  - Alcohol Used as Disinfectant before Venipuncture does not Lead to Sample
      Haemolysis or Sample Dilution.
AB  - INTRODUCTION: Sample haemolysis is often the leading cause of sample rejections
      in clinical laboratory. Isopropyl alcohol or ethyl alcohol, used as disinfectant
      during sample collection is often considered an important cause of sample
      haemolysis or sample dilution; although there is a paucity of scientific
      documentation verifying the same. AIM: To verify whether avoidance to wipe out
      alcohol from the venipuncture site, before sample collection leads to sample
      haemolysis; or leads to sample dilution. MATERIALS AND METHODS: This was a
      prospective randomized study, where every second patient coming to the
      phlebotomist during the study period, in the age group of 20 to 50 years, was
      considered for the study. A total of 60 patients were considered for the study.
      For unbiased comparison sample were collected from both left upper limb (alcohol
      dry) and right upper limb (alcohol wet) of all the patients. Visual inspection
      for haemolysis was done, and serum potassium (K), Calcium (Ca), Lactate
      Dehydrogenase (LDH), Aspartate transaminase (AST), Alanine transaminase (ALT),
      Alkaline phosphatase (ALKP) and Glucose were estimated in both the set. Also
      experiences of patients in both limb collections were considered. RESULTS: On
      visual inspection none of the sample was haemolysed. 51.67% of the patients
      experienced same level of discomfort in both limbs (alcohol dry and alcohol wet)
      during venipuncture. While 28.3% experienced burning sensation in alcohol wet
      limb, another 20% experienced a more soothing sensation in the alcohol wet limb
      during venipuncture. There is no statistically significant difference in the
      measured value of serum K, LDH, Ca, AST, ALT and ALKP and Glucose between the two
      sets of sample - alcohol dry and alcohol wet. CONCLUSION: The study concludes
      that avoidance to wipe alcohol before venipuncture does not lead to sample
      haemolysis or sample dilution. Also most patient experienced same or more
      soothing sensation in alcohol wet limb. Therefore sample can be collected without
      a waiting period for alcohol to dry off, thereby preventing haemoconcentration
      and decreasing sample collection time.

PMID- 27042447
TI  - Chemotherapy: Impact on Anti-Mullerian Hormone Levels in Breast Carcinoma.
AB  - INTRODUCTION: Anti-Mullerian Hormone (AMH) is a glycoprotein of the transforming
      growth factor-beta (TGF-beta) family that seems to reflect the continuous non
      cyclical growth of small follicles and can be considered an indirect index of the
      size of the resting primordial follicle pool. Accordingly, AMH represents a
      marker of Ovarian Reserve (OR) and is particularly useful in demonstrating
      ovarian tissue damage induced by chemotherapy. AIM: To evaluate and compare the
      levels of AMH in Breast Carcinoma patients before and after chemotherapy with age
      matched healthy controls and to assess whether AMH as a biochemical marker of the
      OR might improve prediction of chemotherapy related outcomes in these patients.
      MATERIALS AND METHODS: The present study was conducted in the Department of
      Biochemistry in collaboration with Department of Radiotherapy, Pt. B.D. Sharma,
      University of Health Sciences, Rohtak between June 2013 and June 2014. The
      subjects were divided into two groups. A total of 30 female patients of confirmed
      diagnosis of breast carcinoma were enrolled in the study group (Group I). The
      enrolled breast cancer cases were further divided into subgroups (Group
      IA=Prechemotherapy & Group-IB= Postchemotherapy). Thirty healthy age matched
      female volunteers were enrolled as controls (Group II). Serum levels of AMH were
      determined by the ultrasensitive anti-mullerian hormone/ mullerian inhibiting
      substance (US AMH/MIS) Enzyme Linked Immuno Sorbent Assay (ELISA). RESULTS: There
      was a significant decrease in serum AMH levels in the both study group-IA and
      study group-IB as compared to control group-II (p<0.05 and p<0.001 respectively).
      The prechemotherapy (group-IA) serum AMH levels dropped significantly after
      chemotherapy (group-IB) (p<0.001). CONCLUSION: AMH levels declined after
      chemotherapy indicates direct chemotherapy induced damage to the granulosa cells
      and growing follicles, reflecting decrease ovarian reserve and fertility.

PMID- 27042448
TI  - Haematopoietic, Antioxidant and Membrane Stabilizing Property of Diallyl
      Disulphide in Irradiated Mice.
AB  - INTRODUCTION: Diallyl disulphide is an organo-sulphur compound which is present
      in garlic and responsible for the characteristic odor of garlic. It is known for
      its anticancer and invitro membrane stabilizing properties. AIM: The main aim was
      to evaluate the haematopoietic, antioxidant and membrane stabilizing property of
      diallyl disulfide in irradiated mice. MATERIALS AND METHODS: Mice were grouped
      into 6 groups as control, drug control, radiation control and drug pre-treatment
      groups (i.e. drug administration + radiation group) The mice were fed orally for
      15 consecutive days and on the 15(th) day, one hour after drug administration,
      the mice were irradiated with 6Gy electron beam radiation. The changes in blood
      cell count, total antioxidant levels, malondialdehyde and reduced glutathione
      levels were determined. The immunomodulatory response of DADS to the radiological
      effects was determined by the estimation of IL-6 levels. RESULTS: A significant
      improvement in pre-drug treatment group when compared to control groups in the
      haemoglobin, red blood cell count, white blood cell count, haematocrit and
      platelet counts was observed. There is an increased level of interleukin-6 in the
      drug treated groups compared to the radiation control. An increase in the
      malondialdehyde levels and decrease in the glutathione levels in the irradiated
      group indicate increased lipid peroxidation and oxidative stress, whereas, there
      is a significant reduction in the malondialdehyde levels and increased
      glutathione levels in the drug pre-treatment groups showing membrane
      stabilization. CONCLUSION: Thus DADS proves to be an effective haematopoietic and
      antioxidative agent to counter radiation induced haematopoietic suppression and
      oxidative stress.

PMID- 27042449
TI  - Awareness about Research Ethics among General Practitioners not Attached with
      Research Institutions.

PMID- 27042450
TI  - Effect of Left, Right and Alternate Nostril Breathing on Verbal and Spatial
      Memory.
AB  - INTRODUCTION: Yoga has beneficial effects on memory. In females, left hemisphere
      of the brain is responsible for verbal memory and right hemisphere is responsible
      for the spatial memory, while the opposite is true for males. AIM: Aim of the
      present was to study the effect of unilateral right nostril breathing, left
      nostril breathing and alternate nostril breathing on verbal and spatial memory
      scores. MATERIALS AND METHODS: A total of 51 female subjects (age 18-25 years,
      mean+/-SD =21.71+/-3.11) were taken and divided into three groups (n=17). Each
      group was imparted one of the three different types of nostril breathing
      practices such as Right Nostril Breathing (RNB), Left Nostril Breathing (LNB) and
      Alternate Nostril Breathing (ANB) for 1 week for 45 minutes daily. Subjects were
      given the memory test, before and after 45 minutes of intervention for three
      consecutive days. Memory tests were performed by using Wechsler Adult Intelligent
      Scale. STATISTICAL ANALYSIS: Results were analysed by ANOVA with SPSS version
      17.0. RESULTS: Results showed that there was increase in recall of digit span
      forward, digit-span backward, associate learning and spatial memory scores with
      RNB, LNB and ANB, which were statistically highly significant(p<0.005).
      CONCLUSION: Inclusion of nostril breathing in exercise regimen may be helpful in
      improving recall of memory.

PMID- 27042451
TI  - Using Korotkoff Sounds to Detect the Degree of Vascular Compliance in Different
      Age Groups.
AB  - INTRODUCTION: The principle behind the generation of the Korotkoff sounds is the
      turbulence of blood flowing through a partially occluded area in the artery. With
      increasing age, the vascular wall compliance is expected to decrease, which is
      due to the thickening of the vessel wall, due to which the amplitude of the
      transmitted Korotkoff sounds is decreased. There is also an accompanying rise in
      the systolic B.P. and pulse pressure. AIM: To record and compare the amplitudes
      of the intermediate Korotkoff sounds and the blood pressures in individuals of
      the two age groups, and calculate the pulse pressure and determine whether they
      vary in relation to the amplitude of the intermediate Korotkoff sounds recorded.
      MATERIALS AND METHODS: The cross-sectional study was conducted on 50 young
      subjects (15-25 years) and 50 older subjects (50-70 years). The mid arm
      circumference was measured using a tape. A phonoarteriogram was placed over the
      left brachial artery and the sphygmomanometer cuff was tied 2cm above the cubital
      fossa of the left arm. The blood pressure was recorded using the Lab Tutor
      software. The Korotkoff sounds picked up and transmitted by the phonoarteriogram
      are represented as distinct lines on the graphical recording. STATISTICAL
      ANALYSIS: Independent samples t-test to look for significant mean amplitude
      differences and for correlating mean amplitude and pulse pressure. Null
      hypothesis rejected at p<0.05. Data analysed using the SPSS software version 20.0
      (SPSS Inc.). RESULTS: There was a significant difference in the mean amplitudes
      of Korotkoff sounds among the different age groups (p=0.001) and subject
      categories (p=0.043 among males, p=0.037 among females). A significant difference
      in pulse pressures was also seen among different age groups and subject
      categories. The decrease in the amplitudes of Korotkoff sounds in the older age
      group accompanies the increase in pulse pressures seen in this group and the same
      was seen among the different age groups within each sex (r=-0.574, p=0.001 among
      males) and (r=-0.449, p=0.002 among females). CONCLUSION: Measuring the amplitude
      of Korotkoff sounds can give us an idea of the nature of the arterial wall as
      shown by a decrease in amplitude in older individuals when compared to the
      younger individuals and of the volume of blood flowing through the artery as
      shown by the higher amplitudes observed in males when compared to females.

PMID- 27042452
TI  - Hearing Impairment and High Blood Pressure among Bus Drivers in Puducherry.
AB  - INTRODUCTION: Noise Induced Hearing Loss (NIHL), a major heath concern due to
      constant exposure to loud noise is on the rising trend in today's world. The bus
      drivers are more vulnerable to the auditory and non-auditory ill effects of noise
      pollution. AIM: The aim of this study was to assess and compare the hearing
      level, blood pressure and peak expiratory flow rate of bus drivers and
      individuals employed in office jobs. MATERIALS AND METHODS: Fifty male bus
      drivers aged 30-50 years and fifty males of the same group employed in office
      jobs were recruited as the test and control groups respectively. The hearing
      level of the individuals in both the groups was assessed using the Hearing
      Deterioration Index (HDI). The lung function and cardiovascular status of the
      study participants were assessed by measuring their Peak Expiratory Flow Rate
      (PEFR) and Blood Pressure (BP) respectively. The mean HDI, PEFR and BP values of
      both the groups were compared using the unpaired t-test and the extent of
      correlation between HDI, service years, exposure level, systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) was determined using Pearson correlation
      coefficient test. RESULTS: HDI, SBP and DBP were significantly higher among the
      bus drivers when compared to the controls. However, there was no significant
      difference in the PEFR values between the test and the control groups. There was
      a highly significant positive correlation between HDI and service years and
      exposure level. Similarly, there was a significant positive correlation between
      exposure level and systolic and diastolic blood pressure. CONCLUSION: Prolonged
      exposure to high intensity of sound results in deterioration of hearing capacity
      and increase in blood pressure among the bus drivers.

PMID- 27042453
TI  - Assessment of Anthropometric Indices, Salt Intake and Physical Activity in the
      Aetiology of Prehypertension.
AB  - INTRODUCTION: Globally, prehypertension is responsible for approximately 62% of
      cardiovascular and 49% of ischemic heart disease (IHD) episodes. Current data
      from the Indian subcontinent suggests that prevalence of prehypertension was 47%
      amongst young urban residents. Considering its serious prognosis, the current
      study was undertaken to assess risk factors such as for cardiovascular diseases
      in prehypertensives adult males in Uttarakhand region. MATERIALS AND METHODS:
      This cross-sectional analytical study was conducted in the Department of
      Physiology, HIMS, Dehradun, over a period of 12 months. Volunteers (20-40 years)
      were divided into two groups; Group I (Controls): normotensives and Group II
      (Cases): prehypertensives based on JNC VII classification. RESULTS: Exercise
      capacity, determined by peak VO2 consumption was significantly lower in
      prehypertensive group than the normotensive group (p<0.001). Daily salt intake of
      pre-hypertensives was significantly greater than the normotensive subjects
      (p<0.001). Multiple Linear Regression analysis revealed that average baseline SBP
      increases by 0.34 mmHg for every 1 kg increase in weight and average baseline DBP
      increases by 0.25 mmHg for every 1 year increase in age. CONCLUSION: Exercise
      capacity was found decreased in pre-hypertensives and they have high daily salt
      intake. Also, weight and age emerged as independent risk factors for SBP and DBP
      respectively.

PMID- 27042454
TI  - Assessment of Cardiac Autonomic Functions in Medical Students With Type D
      Personality.
AB  - INTRODUCTION: Type D personality experiences joint occurrence of Negative
      Affectivity and Social Inhibition. It is an emerging risk factor for
      cardiovascular disease, with prevalence being 18-53% among cardiac patients. Type
      D personality people have exaggerated cardiovascular activity mediated by
      increased sympathetic drive and decreased vagal control of the heart which leads
      to enhanced risk of hypertension and is an independent risk factor for coronary
      heart disease. AIM: To compare the cardiac autonomic function of Type D and non
      Type D students. To compare cardiac autonomic functions among male and female
      students and students with and without family history of hypertension and
      coronary artery disease among Type D. To find the most affected test among Type D
      students. MATERIALS AND METHODS: Thirty Type D and 30 non- Type D medical
      students were identified by DS14. The Parasympathetic cardiac autonomic tests
      done assessed Heart Rate response to valsalva manoeuvre, immediate heart rate
      response to standing and heart rate variation during deep breathing. Sympathetic
      tests assessed BP response to standing and Sustained Hand Grip. The heart rate
      and R-R interval measurement were got from lead II of ECG recordings on Polyrite
      D. Statistical analysis was done using SPSS software. Unpaired student's t-test
      was used and p-value <0.05 was considered to be statistically significant.
      RESULTS: Type D students showed slightly decreased parasympathetic activity and
      increased sympathetic activity when compared to non-Type D students even though
      there was no statistically significant difference between them. There is a
      statistically significant decrease in valsalva ratio among females (p<0.01) when
      compared to males. There is a statistically significant decrease in 30:15 ratio
      and BP response to handgrip (p<0.05) among students with family history of
      hypertension and coronary artery disease when compared with students with no
      family history of coronary artery disease. Valsalva ratio is the most affected
      test in Type D students. CONCLUSION: Cardiac autonomic functions of Type D
      personality persons without cardiovascular disease is not different from that of
      non-Type D. Regular follow up studies over years are required to find if Type D
      personality is associated with cardiovascular risk in healthy individuals.

PMID- 27042455
TI  - A Prediction Formula for Double Product in Pregnancy.
AB  - INTRODUCTION: Maternal cardiovascular changes in pregnancy are numerous and
      increase in double product throughout pregnancy is the part of the same process.
      Double product is a cardinal surrogate of the myocardial oxygen demand and
      cardiac workload. It is the product of heart rate and systolic blood pressure and
      an important determinant of cardiovascular risk in hypertensive patients. AIM:
      This study was intended to determine the double product by comparing normal
      individuals with different trimesters of pregnancy. MATERIALS AND METHODS: A
      cross sectional study was conducted in 220 healthy women in the age range of 18
      35 years with 60 subjects each in 1(st), 2(nd) and 3(rd) trimesters and 40 non
      pregnant subjects as control group. Cardiovascular parameters were recorded in
      both the groups. Statistical analysis was done by comparison of parameters using
      one-way ANOVA and post-hoc by Tukey-Krammer test. Correlation of double product
      and weeks of pregnancy was done using Pearson's correlation. Regression analysis
      was done to know the predictor of double product. RESULTS: It was observed that
      there was statistically very highly significant increase (p=0.000) in the double
      product throughout the pregnancy and duration of pregnancy was found to be the
      predictor of the product. CONCLUSION: The increase in the double product is due
      to increase in heart rate and stroke volume. Double product is the useful
      predictor for early identification of preeclampsia and acute myocardial
      infarction in pregnant women when compared to normal non- pregnant women and
      hence helps in the early management of complications.

PMID- 27042456
TI  - Visual Evoked Potential Response Among Drug Abusers- A Cross Sectional Study.
AB  - INTRODUCTION: There is important preclinical evidence that substance abuse may
      produce neurophysiological disturbances particularly in relation to altered
      neural synchronization in Visual Evoked Potentials (VEP). AIM: The purpose of
      current study was to compare the latencies and amplitudes of different waveforms
      of VEP among different drug abusers and controls and also to identify early
      neurological damage so that proper counseling and timely intervention can be
      undertaken. MATERIALS AND METHODS: VEP was assessed by Data Acquisition and
      Analysis system in a sample of 58 drug abusers, all males, within age group of 15
      45 years as well as in age matched 30 healthy controls. The peak latencies and
      peak to peak amplitudes of different waveforms were measured by applying one-way
      Anova test and unpaired t-test using SPSS version 16. RESULTS: In between drug
      abusers and controls, the difference in the duration of N75 and P100 waveform of
      VEP was found to be statistically highly significant (p<0.001) in both the eyes.
      Also the amplitude of wave P100 was found to be decreased among drug abusers in
      both eyes. CONCLUSION: Chronic intoxication by different drugs has been
      extensively associated with amplitude reduction of P100 and prolonged latency of
      N75 and P100 reflecting an adverse effects of drug dependence on neural
      transmission within primary visual areas of brain.

PMID- 27042457
TI  - Vestibular Stimulation for Stress Management in Students.
AB  - INTRODUCTION: Although several methods are developed to alleviate stress among
      college students, logistic limitations in adopting them have limited their
      utility. AIM: Hence, we aimed to test a very practical approach to alleviate
      stress among college students by achieving vestibular stimulation using swings.
      MATERIALS AND METHODS: In this study 60 male and female participants were
      randomly assigned into vestibular stimulation or control groups. Depression,
      anxiety, stress scores, sleep quality, heart rate, blood pressure, Autonomic
      functions, respiratory, haematological, cognitive function, Quality of life were
      recorded before and after 1(st), 7(th), 14(th), 21(st), 28(th) days of vestibular
      stimulation. RESULTS: STAI S and STAI T scores were significantly improved on day
      28(th) following vestibular stimulation. Diastolic and mean arterial blood
      pressure were significantly decreased and remained within normal limits in
      vestibular group on day 28(th) following vestibular stimulation. Postural fall in
      blood pressure was significantly improved on day 14 onwards, following vestibular
      stimulation. Respiratory rate was significantly improved on day 7 onwards,
      following vestibular stimulation. PSQI sleep disturbance, PSQI sleep latency,
      PSQI total score and bleeding time was significantly improved following
      vestibular stimulation. CONCLUSION: Our study supports the adoption of vestibular
      stimulation for stress management. Hence, placement of swings in college campuses
      must be considered, which may be a simple approach to alleviate stress among
      college students.

PMID- 27042458
TI  - Chloramphenicol - A Potent Armament Against Multi-Drug Resistant (MDR) Gram
      Negative Bacilli?
AB  - INTRODUCTION: Multidrug-resistant gram-negative bacteria cause infections which
      are hard to treat and cause high morbidity and mortality. Due to limited
      therapeutic options there is a renewed interest upon older antimicrobials which
      had fallen into disuse as a result of toxic side effects. One such antibiotic is
      chloramphenicol which was sidelined due to reports linking its use with the
      development of aplastic anaemia. AIM: A study was conducted to evaluate the
      susceptibility of chloramphenicol in light of the emerging problem of multi-drug
      resistant gram negative bacteria (MDR GNB). MATERIALS AND METHODS: A total of 483
      MDR GNB of the 650 consecutive Gram Negative Bacteria isolated from various
      clinical samples of patients admitted at a tertiary care hospital in Jaipur
      between January-June 2014 were screened for chloramphenicol susceptibility by the
      disc diffusion method as per CLSI guidelines. RESULTS: The MDR GNB isolates were
      obtained from 217 (45%) urine, 163 (34%) from respiratory samples, 52(11%) from
      pus, 42 (9%) from blood and 9 (2%) from body fluids. A 68% of the MDR GNB
      isolates were found to be sensitive to chloramphenicol. CONCLUSION: Clinicians
      should always check for the local susceptibility of Gram-negative bacteria to
      chloramphenicol. This antibiotic has a potential to play a role in the
      therapeutic management of infections due to MDR GNB pathogens.

PMID- 27042459
TI  - Detection of Vancomycin Resistance among Enterococcus faecalis and Staphylococcus
      aureus.
AB  - INTRODUCTION: Vancomycin remains the drug of choice for resistant gram positive
      infections caused by Enterococcus spp and Methicillin resistant Staphylococcus
      aureus (MRSA). Increased use of vancomycin has led to frank resistance and
      increase in MIC (MIC creep). Vancomycin intermediate Staphylococcus aureus
      (VISA), Vancomycin resistant Staphylococcus aureus (VRSA) & Vancomycin resistant
      Enterococci (VRE) are important emerging nosocomial pathogens resulting in
      treatment failures. AIM: This study was undertaken to detect vancomycin
      resistance among clinical isolates of Staphylococcus aureus and Enterococcus
      faecalis by phenotypic and genotypic methods. MATERIALS AND METHODS: The study
      was conducted in a 1850 bedded university teaching hospital from November 2013 to
      April 2014. Non-repetitive, consecutive clinically significant Staphylococcus
      aureus (109) and Enterococcus faecalis (124) were included in this study. They
      were identified up to species level by conventional and automated methods.
      Susceptibility to various antibiotics was tested by disc diffusion method. MIC of
      vancomycin was determined by agar dilution method. Inducible resistance to
      clindamycin was detected by the D test. Methicillin resistance in Staphylococcus
      aureus (MRSA) was screened using cefoxitin disc. All isolates were subjected to
      polymerase chain reaction (PCR) to detect van A and van B genes. RESULTS: Out of
      109 Staphylococcus aureus isolates, 54 were MRSA. By MIC there was no resistance
      observed to vancomycin.MIC50 was 1MUg/ml. None of the isolates harboured van A
      and van B. Among Enterococcus faecalis, sixteen isolates (12.9%) and four
      isolates (3.2%) exhibited resistance to vancomycin and teicoplanin by disc
      diffusion respectively. All isolates were susceptible to linezolid. Van A was
      detected in 2, van B in 7 and one had both van A and van B. CONCLUSION: PCR
      remains the gold standard for diagnosis of vancomycin resistance. There was no
      resistance observed to vancomycin among Staphylococci though the MIC creep
      detected is a cause for concern. Eight percent of Enterococci were vancomycin
      resistant.

PMID- 27042460
TI  - Characterization of Extended-Spectrum Beta-lactamase from Escherichia coli and
      Klebsiella Species from North Eastern Nigeria.
AB  - INTRODUCTION: Resistance to antimicrobials has become a serious global health
      concern complicating treatment strategies and increasing health-care costs. The
      extended-spectrum beta-lactamase producing bacteria stand out as bacteria of
      great epidemic concern among Gram negative bacilli. Control and appropriate
      interventions for antimicrobial resistance depend on effective surveillance and
      knowledge of the patterns and determinants of resistance. AIM: The present study
      was undertaken to detect and characterize ESBLs in Escherichia coli and
      Klebsiella Species from University of Maiduguri Teaching Hospital, Maiduguri,
      North-Eastern Nigeria. MATERIALS AND METHODS: Confirmed variants of Escherichia
      coli and Klebsiella Species isolated from 439 patients that were admitted in
      various units of University of Maiduguri Teaching Hospital (UMTH) were screened
      for ESBL using CLSI breakpoints. Suspected ESBLs producers were subjected to
      confirmation using double disk synergy method. Detection of ESBL genes was
      further done by multiplex PCR. RESULTS: Out of the 439 isolates screened; the
      result shows 147 (33.5%) were ESBL producers but only 121(23.6%) were confirmed
      by the double disk synergy method. The prevalence of ESBL amongst the organisms
      were; 41/172 (23.8%) for Escherichia coli and 80/267/(30.0%) for Klebsiella
      Species. Based on PCR analysis, the various percentage genotypes of the ESBL
      producers were 44 (36.4%) for SHV gene followed by 38(31.4%) for TEM gene and the
      lowest of 33(27.3%) for CTX-M gene. CONCLUSION: ESBLs are prevalent among Species
      of Escherichia coli and Klebsiella Species in Maiduguri, Borno State, not only
      are there TEM and SHV but also CTX-M types. Antibiotic stewardship program to
      maximise use of available antibiotics is underscored as well as coordinated
      national efforts in combating resistance.

PMID- 27042461
TI  - Prevalence of MRSA Nasal Carriage in Patients Admitted to a Tertiary Care
      Hospital in Southern India.
AB  - INTRODUCTION: Infections with MRSA, both community and hospital acquired, are
      well established and the source of infection is often a carrier. There are very
      few studies showing the magnitude of MRSA nasal colonization among healthy
      persons from the community. This study was conducted to detect the prevalence of
      MRSA nasal carriage in patients who did not have any known risk factors
      associated with HA- MRSA colonization, admitted to a tertiary care centre in
      Kerala. MATERIALS AND METHODS: Nasal swabs were collected from patients within 24
      hours of admission. Specimen were inoculated on chromogenic agar (HiCrome MeReSa
      agar-HiMedia) for MRSA screening. Isolates were then subjected to antibiotic
      sensitivity tests, SCCmec typing and PVL gene detection. RESULTS: Out of 683
      patients, 16 carried MRSA in their nares (2.3%). Of the 16 strains 13 (81.25 %)
      strain were SCCmec type III and one belonged to SCCmec type IV (6.25 %). Two
      strains failed to amplify SCCmec genes. Three strains carried genes for PVL toxin
      (18.75%). CONCLUSION: With a better understanding of the complex epidemiology of
      MRSA it is increasingly apparent that demarcations between the HA and CA
      phenotypes are not as clear cut as previously thought. In this study of nasal
      carriage of MRSA in the community we have demonstrated prevalence consistent with
      published data. Most isolates however were shown to belong to the type
      conventionally assigned to HA-MRSA.

PMID- 27042462
TI  - Alteration of T Cell Subtypes in Beta-Thalassaemia Major: Impact of Ferritin
      Level.
AB  - INTRODUCTION: Oxidative damage and regular antigenic stimulation are main factors
      in accelerating immunosenescence. The present study was conducted to investigate
      new concepts of early immunosenescence in thalassaemia patients. MATERIALS AND
      METHODS: Twenty seven beta-thalassaemia major patients and a group of matched
      healthy volunteers aged 10-30 years in Shahrekord, Iran were recruited into the
      study. Ferritin level was determined and CD4 or CD8 T cells were analysed versus
      phenotyping markers, CD27, CD28, CD57 and CCR7, by flowcytometry. Data were
      analysed by Mann-Whitney and Spearman's correlation coefficient test in SPSS
      11.5. RESULTS: Absolute lymphocytosis and partial decrease in T cells were
      observed in the patients. CD4+CD57+ and CD4+CCR7- T cells were significantly
      higher, whereas CD8+CD27+ and CD8+CCR7+ T cells were partially higher in
      patients. A negative correlation was observed between ferritin level and number
      of CD8+CD27+ and CD8+CCR7+ T cells, whereas the correlation was positive between
      ferritin level and number of CD57+ T cells. CONCLUSION: Moderate alteration of T
      cell repertoire and increase in CCR27-, CCR7-, and CD57+ T cells could reflect
      antigenic stimulation, decline in naive T cells, and being closer to terminally
      differentiated cells. Effect of iron overload is potentially explained by
      positive correlation of blood transfusion and ferritin level with frequency of
      CD3+CD27- and that of ferritin with frequency of CD57+ T cells.

PMID- 27042463
TI  - Evaluation of Genotypic and Phenotypic Methods for Detection of Methicillin
      Resistant Staphylococcus aureus in a Tertiary Care Hospital of Eastern Odisha.
AB  - INTRODUCTION: Methicillin resistant Staphylococcus aureus has emerged as an
      important pathogen in nosocomial and community acquired infections. Accurate and
      rapid identification of MRSA in clinical specimens is essential for timely
      decision of effective antimicrobial chemotherapy. AIM: The present study was
      conducted to compare efficacy of four conventional phenotypic methods, with mec-
      A based polymerase chain reaction (PCR) for MRSA identification. MATERIALS AND
      METHODS: Methicillin resistance was determined in 200 S.aureus isolates by
      oxacillin disc diffusion, cefoxitin disc diffusion, Oxacillin Resistance
      Screening Agar and E-test. The results were compared with mec-A based PCR.
      RESULTS: Among 200 S.aureus isolates 62 (31%) were positive for mec-A gene by
      PCR. Cefoxitin disc diffusion, Oxacillin Resistance Screening Agar and E-test
      showed 100% specificity. Oxacillin disc diffusion had lowest sensitivity (82.5%)
      and specificity (98.5%) among all. The conventional methods take more time than
      PCR for diagnosing MRSA. Linezolid, Vancomycin & Dalfopristin were the highly
      sensitive drugs against MRSA isolates. CONCLUSION: Cefoxitin disc diffusion, is
      rapid, simple and cheaper, hence can be used routinely as an alternative to PCR
      for detection of MRSA in resource constraint laboratories.

PMID- 27042464
TI  - Can EDTA Change MRSA into MSSA? A Future Prospective!
AB  - INTRODUCTION: In the present era we are left behind with limited options for the
      treatment of serious infections caused by multidrug resistant S.aureus, most
      remarkably nosocomially acquired Methicillin resistant S.aureus (MRSA). The
      problem increases more when these strains easily become multidrug resistant (MDR)
      due to biofilm formation. Those staphylococcal species that are vancomycin and
      linezolid resistant are also resistant to other antistaphylococcal agents which
      call for an urgent intervention to develop newer antimicrobial agents. AIM: The
      present study was undertaken with the aim to evaluate the antibiofilm effect of
      EDTA against the biofilm forming MRSA isolates, isolated from different clinical
      infections. MATERIALS AND METHODS: The biofilms formed on polystyrene microtitre
      plates by the MRSA strains were treated by different concentrations of EDTA to
      find out its anti-biofilm activity. Further simultaneously the antibiotic
      susceptibility pattern was noted down to check whether the MRSA strains become
      MSSA (Methicillin sensitive S.aureus). RESULTS: Our data demonstrates that EDTA
      at 4mM concentration inhibits biofilm of MRSA and at 20 mM have an ability to
      reduce and dissociate the biofilm membrane, allowing the antibiotics to enter and
      convert MRSA strains into MSSA. CONCLUSION: These findings suggest that
      commercially available EDTA could be used in future to control MRSA and its
      biofilm- related infections.

PMID- 27042465
TI  - Utility of Serological Tests in the Era of Molecular Testing for Diagnosis of
      Human Brucellosis in Endemic Area with Limited Resources.
AB  - BACKGROUND: The culture has always been the gold standard test for diagnosis of
      human brucellosis but the conventional Brucella diagnostic tests viz. serology
      and culture are often beset with poor specificity & sensitivity respectively. The
      culture positivity rates for Brucella vary from 92% for bone marrow to 10% for
      non-blood samples and also dependent on the type of sample. The primary immune
      determinant for Brucella species is the cell wall surface lipopolysaccharide,
      which is antigenically similar to other gram-negative rods. Hence, Brucella
      serological tests cross react with Escherichia coli 0116 and 0157, Salmonella
      urbana, Yersinia enterocolitica 0:9, Vibrio cholerae, Xanthomonas maltophilia and
      Afipia clevellandensis infections, which are common in developing countries also
      having higher incidence of brucellosis. AIM: The aim of the study was evaluation
      of conventional serological techniques and PCR for diagnosis of human brucellosis
      in and around north Karnataka which is endemic for brucellosis and patients often
      present with elevated base line antibody titers and confounding clinical
      manifestations. MATERIALS AND METHODS: Blood/serum samples of 400 patients
      suffering from acute undifferentiated fever (AUF) were subjected to culture,
      Brucella slide agglutination test (SAT), standard tube agglutination test (STAT
      coupled with 2 ME) and PCR. RESULTS: Of the 400 AUF patients, anti-Brucella
      antibodies were detected by SAT and STAT in serum of 35 and 34 patients
      respectively. IS711 gene for Brucella was identified in 32 patients by PCR.
      Twenty samples yielded Brucella in culture on biphasic medium with average
      incubation period of 9 days. All patients having titer of >= 160IU / ml in STAT
      were found positive by PCR also. CONCLUSION: Brucella STAT corroborated well with
      PCR results in all those cases where antibodies were present at least one
      dilution above cut-off value of 80 IU/ml. We probably need to raise cut-off
      titers to >=160 IU/ml because of endemic region. The SAT was upheld as very good
      quick, easy to perform and economical screening test for human brucellosis. SAT
      as rapid screening test and STAT as more definitive test can be very well adopted
      by laboratories working in resource scarce settings for diagnosis of human
      brucellosis in absence of PCR even for population with normally elevated
      antibodies levels due to residing in Brucella endemic areas.

PMID- 27042466
TI  - Dioctophymiasis: A Rare Case Report.
AB  - Dioctophyma renale commonly known as "giant kidney worm' is found in the kidney
      of carnivorous mammals. Human infestation is rare, but results in destruction of
      the kidneys. Very few cases have been reported worldwide. We are here reporting a
      case of Dioctophymiasis in a 35-year-old male patient who presented with
      retention of urine and subsequent passage of worm and blood in urine. The worm
      was confirmed as Dioctophyma renale based on its morphology and clinical
      presentation. This is a very rare case report and to best of our knowledge only
      two cases have been reported from India. 

PMID- 27042467
TI  - Malaria and Typhoid Co-infection: Need to Interpret Serological Results
      Cautiously.

PMID- 27042468
TI  - Spectrum of Lesions Affecting the Renal Pelvis and Pelviureteric Junction: A 13
      Year Retrospective Analysis.
AB  - INTRODUCTION: Both, the renal pelvis and the ureter, are affected by
      developmental, reactive and neoplastic disorders, though rare in incidence. AIM:
      This series of cases were analysed to study the clinicopathological
      characteristics of the common and comparatively rare lesions involving the renal
      pelvis and pelviureteric junction. MATERIALS AND METHODS: A retrospective
      collection of 476 nephrectomies and pelviureteric junction resections, received
      over a period of 13 years from 2001 to 2013 was done. The patients' clinical
      details were obtained and the histopathological findings reviewed. The lesions
      were classified into non-neoplastic and neoplastic categories. RESULTS: Primary
      involvement of the renal pelvis and pelviureteric junction was seen in 105 of 476
      specimens. The mean age was 54.5 years with a male to female ratio of 2.2:1. The
      non-neoplastic lesions accounted for 76.2% of cases with a majority being
      pelviureteric junction obstruction due to inflammation induced fibromuscular
      hypertrophy (68.6%) causing hydronephrosis. Urothelial carcinomas were
      encountered in 20% of the cases. A majority of the urothelial carcinomas were
      infiltrative (81%) and high grade (71%) tumours. CONCLUSION: Renal pelvis, a
      conduit to propel urine, can be the site for numerous disorders. Non-neoplastic
      lesions were more common than neoplasms. Pelviureteric junction obstruction due
      to inflammation induced fibromuscular hypertrophy was the commonest lesion in our
      study. In the neoplastic category, urothelial carcinoma was most common. However,
      rare lesions such as hamartomatous fibroepithelial polyp, Von Brunn's nests, flat
      urothelial hyperplasia and intramuscular haemangioma of upper ureter at the
      pelviureteric junction were encountered along with occasional cases of
      tuberculosis and squamous cell carcinomas.

PMID- 27042469
TI  - FNAC Versus Core Needle Biopsy: A Comparative Study in Evaluation of Palpable
      Breast Lump.
AB  - INTRODUCTION: Breast carcinoma is the most common malignant tumour and the
      leading cause of carcinoma death in women in world. The main purpose of FNAC or
      CNB of breast lumps is to confirm cancer preoperatively and to avoid unnecessary
      surgery in specific benign conditions. AIMS AND OBJECTIVE: The objective of the
      study was to compare between Fine Needle Aspiration Cytology (FNAC) and Core
      Needle Biopsy (CNB) in the diagnosis of breast carcinoma with final histological
      diagnosis from excision specimen as it is gold standard. MATERIALS AND METHODS: A
      prospective study was done on 50 cases. Patients undergoing all three procedures
      (Fine Needle Aspiration Cytology and Core Needle Biopsy done at Department of
      Pathology; subsequent excision surgeries done at Department of General Surgery)
      were selected. May Grunwald Giemsa (MGG) and Papaniculou (PAP) staining were
      performed on cytology smears. Haematoxylin and Eosin (H&E) staining was done on
      both the CNB and tissue specimens obtained from subsequent excision surgeries to
      see the histological features. RESULTS: FNAC showed sensitivity, specificity,
      positive predictive value, negative predictive value, and diagnostic accuracy
      were 69%, 100%, 100%, 38.1%, and 74% respectively in diagnosing carcinoma. CNB
      had sensitivity, specificity, positive predictive value, negative predictive
      value, and diagnostic accuracy of 88.3%, 100%, 100%, 53.3% and 86%. Both FNAC and
      CNB showed statistically significant correlation with confirmatory HPE of
      excision specimen (p-value <0.05) in the diagnosis of breast carcinoma.
      CONCLUSION: Fine needle aspiration cytology (FNAC) is a rapid, less complicated,
      economical, reliable and relevant method for the preoperative pathological
      diagnosis of breast carcinoma in a developing nation like ours. If the initial
      FNAC is inadequate, core needle biopsy (CNB) can be a useful second line method
      of pathological diagnosis in order to minimize the chance of missed diagnosis of
      breast cancer.

PMID- 27042470
TI  - Spectrum of Sickle Cell Diseases in Patients Diagnosed at a Tertiary Care Centre
      in Karnataka with Special Emphasis on their Clinicohaematological Profile.
AB  - INTRODUCTION: Sickle cell disease is a monogenic disorder with considerable
      clinical diversity and Sickle haemoglobin is responsible for wide spectrum of
      disorders which vary with respect to severity of anaemia, frequency of crises and
      duration of survival. As they are confused with many other clinically aggressive
      disorders, precision in diagnosis is essential both to proper clinical management
      and subsequent genetic counselling. Hence, this study was taken up in order to
      diagnose these conditions and administer suitable counselling measures to
      minimise the incidence of sickle cell disease in the future. AIM: The aim of this
      study was to identify the spectrum of all Sickle cell diseases diagnosed at a
      tertiary care centre in Bangalore, Karnataka, India who presented over a period
      of five years from 2009 to 2013 and also to screen the parents and siblings of
      the patients for their carrier status. MATERIALS AND METHODS: We reviewed 26
      cases of Sickle Cell Disease (SCD) and also 38 parents & 10 siblings of these
      children for their carrier status. Haemoglobin electrophoreses was performed by
      using alkaline gel method, followed by High Performance Liquid Chromatography
      when needed. RESULTS: A total of 26 children diagnosed with SCD were enrolled in
      the study. Most common entity was Sickle Cell Anaemia (SCA), followed by sickle
      thalassaemia and Sickle Cell Trait (SCT). Commonest clinical presentation was
      fever and pallor. Amongst the parents and siblings, sickle cell trait was the
      most common entity followed by thalassaemia trait. One interesting case of HbSE
      disease was encountered, which is a rare entity in India. CONCLUSION: This study
      brings out the total spectrum of SCDs in a tertiary care centre in Karnataka,
      with more emphasis on screening of the parents and siblings for their carrier
      status.

PMID- 27042471
TI  - Juvenile Granulosa Cell Tumour: Anaplastic Variant with Omental Deposits.
AB  - Juvenile Granulosa Cell Tumour (JGCT) of ovary represents a small fraction of all
      primary ovarian malignancies. It is a subtype of granulosa cell tumour that is
      almost always found during the first three decades of life. Histologically, it
      differs from the typical adult type of granulosa cell tumour. It accounts for 5
      15% of all granulosa cell tumours, majority being unilateral. Herein, we describe
      an unusual histopathological variant of JGCT with numerous large cystic spaces,
      anaplasia and focal syncytiotrophoblast like giant cells. 

PMID- 27042472
TI  - Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour.
AB  - Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction
      of sweat gland tumours. This tumour is found to originate from the
      intraepithelial parts of the sweat glands. It commonly involves the lower
      extremities in elderly patients and carries an aggressive behaviour. Cutaneous
      and visceral metastasis can occur and hence prompt treatment is mandatory.
      Surgical excision is the mainstay of treatment modality. We hereby present a case
      of eccrine porocarcinoma in a 50-year-old male in the right axillary region
      presenting as a verrucous lesion. 

PMID- 27042473
TI  - Natural Killer Cell Lymphoma: A Case with Classification Dilemma.
AB  - Non-Hodgkins lymphoma of the Natural Killer (NK) cell type is rare. World Health
      Organisation recognises 3 NK-cell phenotypic entities; extranodal NK/T cell
      lymphoma, nasal type (ENK/TL); aggressive NK cell leukaemia (ANKL); and chronic
      lymphoproliferative disorders of NK cells (CLPD-NK) which is classified as a
      provisional entity. Though specific clinical, morphological and immunophenotypic
      criteria have been laid down to diagnose these conditions there may however, be
      considerable variations in the clinical presentation making diagnosis difficult.
      We present a case with contrasting clinical and haematopathological findings
      posing difficulty in its diagnosis and classification, and despite the aggressive
      presentation showing favourable response to treatment. 

PMID- 27042474
TI  - Embryonal Hepatoblastoma with Co-existent Glycogen Storage Disease in a Seven
      month-old Child.
AB  - Hepatoblastoma is an uncommon malignant liver tumour diagnosed usually during the
      first three years of life. It presents as abdominal mass with elevated alpha
      fetoprotein levels. The definite diagnosis requires histopathological
      confirmation. Although conditions like Familial Adenomatous Polyposis (FAP) or
      Beckwith-Wiedman Syndrome may be associated with hepatoblastomas, storage
      disorders are uncommonly documented. We describe a rare case of hepatoblastoma
      with co-existent glycogen storage disease in an infant male who presented with a
      progressively increasing mass in abdomen along with failure to thrive. 

PMID- 27042475
TI  - Metastatic Collision Tumour (Papillary Thyroid Carcinoma and Squamous Cell
      Carcinoma) in Cervical Lymph Nodes: An Immunohistochemical Analysis.
AB  - Collision tumours are a rare entity, in this report, we describe a case of 73
      year-old woman presented with a rapid enlargement of left upper cervical lymph
      node (LN) associated with right thyroid nodular goiter. The histopathological
      examination of the excised LN showed definite areas of papillary thyroid
      carcinoma admixed with moderately differentiated squamous cell carcinoma (SCC).
      Thyroglobulin immunostaining was positive in papillary carcinomatous areas
      confirming thyroid gland as a source of metastasis. Then the patient underwent
      total thyroidectomy and neck dissection, which revealed multicentric classic
      papillary thyroid carcinoma with an absence of squamous differentiation on
      extensive sampling. The patient received adjuvant radioactive iodine, but the
      neck swelling was rapidly progressing, ulcerated and infected. Computed
      tomography (CT) revealed left large cervical amalgamated LN and two metastatic
      lung nodules, the patient received 2 cycles of chemotherapy and was planned for
      external beam radiotherapy but she died within 7 months of first presentation.
      Collision tumours pose a diagnostic as well as therapeutic challenge and carry a
      rapidly progressive course and a fatal outcome. SCC is considered as a
      dedifferentiation of papillary thyroid carcinoma, which may appear in metastatic
      site rather than the primary site. 

PMID- 27042476
TI  - Persistent Mullerian Duct Syndrome with Ovarian Endometriosis-A Rare Case Report.
AB  - Persistent Mullerian Duct Syndrome (PMDS) is a rare form of internal male
      pseudohermaphroditism, characterised by presence of Mullerian duct derivatives in
      a genotypic and phenotypic male. It is caused by absence of anti- Mullerian
      hormone or defective functioning of its receptors. We report a case of 19-year
      old cryptorchid male with history of orchideopexy who was clinically and
      radiologically diagnosed as left sided chylocele. A definitive diagnosis of PMDS
      with ovarian endometriosis was made on histopathological examination which is
      important for genetic counselling and to reduce complications like infertility
      and neoplastic transformation. We report this case of PMDS with ovary showing
      evidence of endometriosis for its rarity. 

PMID- 27042477
TI  - Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour
      (GIST) of the Stomach: A Case Report.
AB  - Adenocarcinoma is the most common histological type of gastric tumour, accounting
      for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours
      (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous
      adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the
      stomach is rare and very few cases have been reported in literature. Synchronous
      tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old
      gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and
      underwent surgery. Postoperative histopathologic examination revealed 2
      synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was
      determined to be the aggressive tumour based on histologic features. GIST was
      categorized as a very low risk of malignancy, based on its size and mitosis. The
      patient underwent chemotherapy for adenocarcinoma. He is under follow up and is
      currently disease free. Careful histopathologic evaluation is required to detect
      co-existing rare synchronous tumours. Presence of the second tumour may require
      additional procedures or protocols. 

PMID- 27042478
TI  - Biliary Cystadenoma: A Case Report.
AB  - Biliary cystadenoma is a rare cystic neoplasms of liver that usually occurs in
      middle-aged women characterized by multiloculated cysts with internal septae and
      mural nodules. Unilocular biliary cystadenomas are rare and are difficult to
      differentiate from other cysts by radiology. Biliary cystadenomas are slow
      growing benign lesions that are easily resectable with a reported recurrence rate
      of 90% when the resection is incomplete. We present a case of 65-year-old male
      with unilocular biliary cystadenoma with mesenchymal stroma who presented with
      abdominal pain and distension. Laparotomy followed by cystectomy was done and
      postoperative period was uneventful with no abnormal biochemical, heamatological
      or imaging findings. Preoperative radio-imaging techniques may not always be
      helpful in arriving at a specific diagnosis in such cases. Hence thorough
      sampling and a careful histopathological examination is considered gold standard
      for specific diagnosis. 

PMID- 27042479
TI  - Study of Drug Utilization Pattern for Skin Diseases in Dermatology OPD of an
      Indian Tertiary Care Hospital - A Prescription Survey.
AB  - INTRODUCTION: Skin diseases are the major contributors of disease burden in
      society. It affects individuals of all ages, neonates to elderly. Owing to its
      chronic nature, it causes serious impact on quality of life and financial status
      of the sufferer and his family. The problem gets compounded with the
      inappropriate and irrational use of medicines. Periodic prescription audit in
      form of drug utilization study is a way to improve the quality of prescription
      and curb the menace of irrational prescribing which has become a global
      phenomenon. AIM: This study aims to determine the drug utilization pattern and
      assess the economic burden of the patient with skin disease. MATERIALS AND
      METHODS: It was a prospective, cross-sectional study conducted over a period of
      three months from January to March 2015 in newly diagnosed cases attending
      outpatient department of Skin and VD, IGIMS, Patna. The prescriptions were
      analysed with the help of descriptive statistics and results were expressed in
      percentage. RESULTS: Total 752 prescriptions were analysed during the study. Male
      patients were lesser as compared to female as male to female ratio was 0.88. Over
      50% of patients were in adolescent age group i.e. 21-40 years. Acne (17.95%) was
      most common disease in the study population followed by eczema and
      Dermatophytosis. Among the drugs, antihistaminics (24.13%) were prescribed most
      frequently followed by antifungals and antibiotics. Topical agents constituted
      almost 60% of the total prescription and average number of drugs per prescription
      was 5.13, irrespective of the dosage forms prescribed. CONCLUSION: This drug
      utilization study provides an insight to the prescriber regarding various issues
      related to polypharmacy, cost analysis and prevalent disease pattern in the
      region. This study also suggests periodic evaluation of prescription pattern to
      monitor and improve quality of prescription in other departments of the hospital.

PMID- 27042480
TI  - A Study on Polypharmacy and Potential Drug-Drug Interactions among Elderly
      Patients Admitted in Department of Medicine of a Tertiary Care Hospital in
      Puducherry.
AB  - INTRODUCTION: The proportion of elderly population has been constantly increasing
      over last few years. Polypharmacy is unavoidable in the elderly as they often
      suffer from multiple co-morbidities. Potential drug-drug interaction due to
      polypharmacy and potential inappropriate medication among the elderly must be
      carefully assessed. AIM: To find out polypharmacy and potential drug-drug
      interactions among elderly patients admitted and discharged in Department of
      Medicine. MATERIALS AND METHODS: This study was carried out on 100 patients above
      65 years of age both males and females. Data was collected through review of case
      sheets. Polypharmacy was observed based on admission and discharge prescriptions.
      Frequently occurring drug-drug interactions were assessed using online checks.
      RESULTS: Mean number of drugs prescribed to patients on admission (7.61 +/- 3.37)
      was more than that on discharge (5.48+/-2.46). More than half of these patients
      received 5 to 9 number of drugs. On admission 52.69% potential drug-drug
      interactions were observed and on discharge 52.91%. Most common drug interactions
      observed in both the groups were of moderate grade. CONCLUSION: From the present
      study we can conclude that polypharmacy leads to more potential drug-drug
      interactions. To improve drug safety in this high-risk population, appropriate
      prescribing is very important.

PMID- 27042481
TI  - Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and
      Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study.
AB  - INTRODUCTION: Pro12Ala polymorphism is a missense mutation at codon 12 in
      peroxisome proliferator-activated receptor gamma gene (PPARG). This polymorphism
      is known to be associated with increased insulin sensitivity. Pioglitazone, a
      thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR
      gamma receptor. AIM: To determine the association between Pro12Ala polymorphism
      of the PPARG and variation in therapeutic response to the PPARgamma agonist,
      pioglitazone. MATERIALS AND METHODS: The study was done as a hospital based pilot
      project in 30 patients with type 2 diabetes mellitus, on treatment with
      sulfonylurea or metformin but without adequate glycaemic control. They were
      started on pioglitazone as add on therapy for a period of 12 weeks. The
      participants were categorized as responders and non-responders based on the
      change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by
      polymerase chain reaction-restriction fragment length polymorphism. STATISTICAL
      ANALYSIS: Logistic regression analysis was done to evaluate the associations
      between age, baseline body weight, BMI, waist circumference, waist-hip ratio and
      Pro12Ala variants with the response to pioglitazone. The p-value< 0.05 was
      considered significant. RESULTS: The frequency distributions of PPAR gamma
      genotypes were 80% for Pro/Pro and 20% for Pro/Ala in the study population. Among
      the study participants, 30% were non-responders and 70% responders to
      pioglitazone. A significantly higher frequency of the polymorphism was detected
      in the responders (p=0.005) compared to non-responders group. CONCLUSION: Our
      study suggests that there is a potential association between Pro12Ala
      polymorphism and glycaemic response to pioglitazone.

PMID- 27042482
TI  - Use of Complementary and Alternative Medicine among Osteoarthritic Patients: A
      Review.
AB  - INTRODUCTION: One of the most important indications of complementary and
      alternative medicines (CAM) is in arthritis. The popularity of CAM in arthritis
      is consistently on the rise because of the potential side effects of the
      conventional therapy (Methotrexate) of arthritis. In view of this, it was
      important to summarize the information, for healthcare professionals and the
      patients, about the safety and effectiveness of various CAM use in arthritis.
      MATERIALS AND METHODS: This comprehensive review is based on the content derived
      through a thorough literature search using 5 electronic databases such as Science
      direct, Springer link, PubMed, Jet P and Google scholar. Equivalent terms in
      thesauruses or Medical Subject Heading (MeSH) browsers were used whenever
      possible. We included all the articles those are used CAM medications for the
      treatment of arthritis around the globe and searched for the required articles
      published in English in peer reviewed journals from January 1999 to February
      2014. Reports were then arranged and analysed on the basis of country specific
      studies. RESULTS: Initially, a total of 156 articles were retrieved, after
      further screening, 27 articles were selected according to meet objectives of the
      study and those articles which did not qualify, were excluded. Seventeen
      appropriate studies were finally included in the review. Indeed most of the
      studies that fulfilled the objective of this review were carried out in US (n=8,
      47%), then in India (n=2, 11.76%), UK (n=1, 5.88%), Canada (n=1, 5.88%),
      Australia (n=1, 5.88%), Korea (n=1, 5.88%), Thailand (n=1, 5.88%), Turkey (n=1,
      5.88%) and Malaysia (n=1, 5.88%). CONCLUSION: The review revealed that family,
      friend, past experiences and lack of effectiveness of conventional therapy are
      the major factors that influenced patients' decision of initiating and persisting
      with CAM therapy. The review highlighted the need to conduct future studies by
      using some more specific health related outcome measures.

PMID- 27042483
TI  - State of Science, "Intuition in Nursing Practice": A Systematic Review Study.
AB  - INTRODUCTION: There were many attempts for introducing "intuition" to nursing
      practice, But despite the efficacy, it has been ignored as a valid way of
      knowing. Therefore the current study was conducted for evaluating the state of
      sciences to intuition in nursing practice. MATERIALS AND METHODS: In a systematic
      review study, all researches, published from 1995 to 2014, were searched in the
      databases of "PubMed", using "intuition" and "nursing" keywords. The abstract of
      articles were read in scrutiny, then the related researches selected, thereafter
      the full text of them was assessed carefully. RESULTS: From searching the
      databases, 144 articles with "intuition and nursing" were found, 53 as original
      research, and 15 with inclusion criteria were selected. Most of the studies had
      qualitative approaches design as phenomenology (N=4), content analyses (N=2) and
      grounded theory (N=1), six was done for developing the instrument, and two
      studies have been conducted as descriptive method. CONCLUSION: The results
      revealed the researches about intuition in nursing mostly were conducted with
      qualitative and instrument developing methodology and there is a lack of
      quantitative and trial studies.

PMID- 27042484
TI  - Detection of Tuberculosis in HIV Co-infected Individuals: Use of Multiple ELISA
      Responses to 38kDa, Lipoarabinomannan and ESAT- 6 of M. tuberculosis.
AB  - INTRODUCTION: There is a constant search for more sensitive and specific
      laboratory markers for tuberculosis (TB) infection. The early detection of TB in
      HIV co infected individuals is a diagnostic challenge. This is further compounded
      in those harbouring extrapulmonary disease. AIM: To evaluate the use of multiple
      Enzyme Linked Immunosorbent Assays (ELISA) quantifying antibody responses to
      38kDa, LAM and ESAT-6 M.tb antigens in detection of TB in patients with TB and
      HIV-TB co-infection. MATERIALS AND METHODS: This is a cross-sectional study
      carried out in Hyderabad, India. Patient groups included 124 HIV-TB {62 with
      pulmonary TB (PTB) and 62 with extrapulmonary TB (ETB)}, 39 TB, 56 HIV and 57
      healthy subjects (HS). A combination of anti 38kDa and LAM ELISAs measuring IgG,
      IgM and IgA levels and another ELISA measuring anti ESAT-6 combined antibody
      levels of IgG, IgM and IgA were evaluated. One-way ANOVA was performed to compare
      antibody responses among groups. To assess the efficacy of multiple ELISAs in
      detecting TB, concomitant seropositivity of an individual for all four ELISAs
      were evaluated for sensitivity and specificity. RESULTS: A single ELISA carried
      out to detect TB in HIV patients showed a sensitivity ranging from 39% to 72%.
      The sensitivities of concomitant evaluation of multiple ELISAs were 92% for any
      single, 72% for any two, 44% for any three and 14% for any four. Based on the
      specificities, a simple algorithm for TB detection can be deduced. When four
      ELISAs are positive (specificity 100%) in a patient-confirmed TB; when three
      ELISAs are positive (specificity 98%) - probably TB; when two ELISAs are positive
      (specificity 95%) - possibly TB; and when one ELISA is positive (specificity 70%)
      - suspicion of TB. CONCLUSION: The present study establishes the value of
      combining two or more M.tb antigen based ELISAs to enhance the sensitivity and
      specificity of TB detection in patients with tuberculosis as well as in those co
      infected with HIV.

PMID- 27042485
TI  - Automated Triplex (HBV, HCV and HIV) NAT Assay Systems for Blood Screening in
      India.
AB  - This review is confined to triplex nucleic acid testing (NAT) assays to be used
      on fully automated platform. Around the world, these assays are being used at
      various transfusion medicine centres or blood banks to screen blood units for
      HBV, HCV and HIV. These assay systems can screen up to 1000 blood units for HBV,
      HCV and HIV simultaneously in a day. This area has been dominated by mainly two
      manufacturers: M/s Gen-Probe-Novartis and M/s Roche Molecular Systems. The
      triplex NAT assay systems of both manufacturers are licensed by United States
      Food and Drug Administration. There is not much awareness about the technology
      and procedures used in these assays. The main objective of this review is to
      create awareness about the technology and procedure of these assays. 

PMID- 27042486
TI  - Implementation of Indigenous Electronic Medical Record System to Facilitate Care
      of Sickle Cell Disease Patients in Chhattisgarh.
AB  - INTRODUCTION: Sickle cell disease (SCD) is prevalent in central India including
      Chhattisgarh. Screening for SCD is being carried out by Government of
      Chhattisgarh. Electronic Medical Record (EMR) system was developed and
      implemented in two phases. AIM: Aim was to use informatics techniques and
      indigenously develop EMR system to improve the care of SCD patients in
      Chhattisgarh. EMR systems had to be developed to store and manage: i) huge data
      generated through state wide screening for SCD; ii) clinical data for SCD
      patients attending the outpatient department (OPD) of institute. MATERIALS AND
      METHODS: 'State Wide Screening Data Interface' (SWSDI) was designed and
      implemented for storing and managing data generated through screening program.
      Further, 'Sickle Cell Patients Temporal Data Management System' (SCPTDMS) was
      developed and implemented for storing, managing and analysing sickle cell disease
      patients' data at OPD. Both systems were developed using VB.Net and MS SQL Server
      2012. RESULTS: Till April 2015, SWSDI has data of 1294558 persons, out of which
      121819 and 4087 persons are carriers and patients of sickle cell disease
      respectively. Similarly till June 2015, SCPTDMS has data of 3760 persons, of
      which 923 are sickle cell disease patients (SS) and 1355 are sickle cell carriers
      (AS). CONCLUSION: Both systems are proving to be useful in efficient storage,
      management and analysis of data for clinical and research purposes. The systems
      are an example of beneficial usage of medical informatics solutions for managing
      large data at community level.

PMID- 27042487
TI  - An Epidemiological Study of Malnutrition Among Under Five Children of Rural and
      Urban Haryana.
AB  - INTRODUCTION: A child is future of nation. Malnutrition is a big public health
      problem in India as it can be attributed for more than half (54 percent) of all
      under five mortality in India. AIM: To assess prevalence of malnutrition among
      urban and rural population of Haryana using newly developed WHO growth standards.
      SETTINGS AND DESIGN: A community based cross-sectional survey was conducted in
      children of 3-60 months age living in the urban and rural field practice areas of
      Department of Community Medicine MMIMSR, Mullana, Ambala during January 2012 to
      December 2012. MATERIALS AND METHODS: Seven hundred and fifty children, aged 3-60
      months, were studied for nutritional status, socio-demographic measures were
      obtained from structured questionnaire and followed by anthropometric assessment
      using standards methods. Z score for Anthropometric data was calculated by WHO
      Anthro 2010 software (beta version). STATISTICAL ANALYSIS: Descriptive statistics
      as well as simple proportion were calculated with SPSS 20. RESULTS: We found that
      41.3% children were underweight and 14% were severe underweight. Female children
      were more nutritionally deprived than males. Among sociodemographic factors
      maternal educational and working status as well as SES class and rural background
      of family had greater impact on nutritional status of child. CONCLUSION: We found
      that almost half of our under five children are underweight, girl child being
      affected more. For attainment of best possible nutrition and growth in children,
      targeted short-term strategies addressing underlying risk factors and more long
      term poverty alleviation strategies may be needed.

PMID- 27042488
TI  - University-Based Smoking Cessation Program Through Pharmacist-Physician
      Initiative: An Economic Evaluation.
AB  - INTRODUCTION: Annually, especially in poor resourced countries, significant
      amount of money is spent to treat chronic diseases. The money instead could be
      saved by spending on health promotion programs for preventing chronic diseases.
      AIM: To conduct cost-effectiveness analysis of various intervention modules in
      the "Smoking Cessation" program conducted in Universiti Sains Malaysia (USM).
      MATERIALS AND METHODS: This was an observational study design. Cost-effectiveness
      analysis was used to assess the costs and outcomes of the intervention. Data were
      collected retrospectively from medical records of all clients (n= 129) and then
      all the participants were followed-up for at least 6 months from the date of
      participation. Data were analysed descriptively using frequency (%) and mean
      (sd). Kolmogorov-Smirnov test was carried out to test for normality. Chi-square
      and Kruskal-Wallis tests were used at alpha level of 0.05. All analyses were done
      using SPSS version 19. RESULTS: The findings of the study showed that the
      majority of participants were Malays (n= 108; 83.7%), males (n= 128; 99.2%),
      USM's staff (n= 71; 55.0%) and within an age group of 23 years or less (n= 38;
      29.5%). Among those who successfully quit were male (n= 30; 100%), Malays (n= 29;
      96.7%), staff (n= 19; 63.3%), moreover, their age ranged from 35 to 56-year-old
      (n= 15; 50.0%). Further analysis of data showed that there were significant
      associations between success rate and modules of intervention, occupation,
      motivation factors, and frequency of counselling. Total cost of the Smoking
      Cessation Program was MYR 38,634.66 (during a period of 34.5 months), with a
      success rate equal to 29.1%. The most cost-effective module of intervention was
      counselling alone (CE ratio equal to MYR360.00 per 1% of success rate). The study
      found counselling with patch was ineffective during the study period. CONCLUSION:
      Counselling alone module was the most cost-effective in Smoking Cessation program
      conducted in USM, Malaysia.

PMID- 27042489
TI  - Seroprevalence of Hepatitis B Surface Antigen and Occupational Risk Factors Among
      Health Care Workers in Ekiti State, Nigeria.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection is contracted from blood and
      other body fluid making healthcare workers (HCW) prone to the infection
      especially in the developing world. Though it is a vaccine preventable disease,
      the level of awareness and universal precaution among HCW is low in sub-Saharan
      African and Asia. AIM: The study was aimed at determining the seroprevalence of
      hepatitis B surface antigen and occupational risk factors among health care
      workers at Ekiti State University Teaching Hospital, Ado Ekiti. MATERIALS AND
      METHODS: One hundred and eighty-seven (187) blood samples were collected from
      volunteer subjects who comprised of medical doctors, nurses, health attendants,
      and porters who are in regular contact with blood, body fluids and patients after
      informed consent. Well detailed and structured questionnaires were used to obtain
      demographic and other relevant data from the subjects. Blood samples were tested
      by Enzyme Linked Immunosorbent assay (ELISA) for hepatitis B surface antigen.
      RESULTS: Out of the 187 HCWs there were 91 males (48.7%) and 96 (51.3%) females.
      Only 2 participants tested positive to hepatitis B surface antigen with a
      prevalence of 1.1%. Also, only 30 (16.0%) of the participants had been fully
      vaccinated against the infection while the remaining 157(84.0%) had no adult
      vaccination. CONCLUSION: It is obvious that the awareness of the infection is low
      among the HCWs studied thus the need to incorporate screening for HbsAg and
      vaccination against HBV into the periodic/pre-employment health intervention
      programmes by employers to help in the protection of HCWs and control the spread
      of the virus.

PMID- 27042490
TI  - The Need for Patient Follow-up Strategies to Confirm Diabetes Mellitus in Large
      Scale Opportunistic Screening.
AB  - Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycaemia
      with disturbances of carbohydrate, fat and protein metabolism resulting from
      defects in insulin secretion, insulin action, or both. Type 2 (non-insulin
      dependent) Diabetes mellitus is one of the preventable non communicable disease
      resulting in increased morbidity and mortality in developing countries like
      India. It is characterized by disorders of insulin action and/or insulin
      secretion. Number of people with Type 2 Diabetes is growing rapidly worldwide
      with economic development, ageing populations, increasing urbanisation, dietary
      changes, reduced physical activity and lifestyle changes. The global prevalence
      of diabetes is 9%, while in India it is 8.63% and in Tamil Nadu it is 10.4%.
      National and State programmes on Diabetes control are implemented to combat the
      disease burden. A detailed review of the programme modules, operational
      guidelines and visit to health facilities were done to understand the
      implementation process related to control of Diabetes mellitus. As part of these
      programmes, opportunistic screening is implemented for target population. Though
      these programmes are unique, there are few lacunae identified which are missing
      opportunities and time consuming. There are no strategies so far in such
      programmes to make the screened positive cases to undergo confirmatory tests.
      Since screening is only opportunistic, the screened positive cases can be
      subjected to undergo confirmatory tests by different methods. The specified roles
      and responsibilities of health staffs at various levels to ensure follow up
      should also be framed and followed. The objective of this article is to review
      the existing strategies and to suggest the need for follow up pathways to be
      adopted from the first contact level to the level of final confirmation for
      better compliance. 

PMID- 27042491
TI  - Comparative Study of Two Different Myringoplasty Techniques in Mucosal Type of
      Chronic Otitis Media.
AB  - INTRODUCTION: Myringoplasty is a surgical procedure used to close the perforation
      of pars tensa of the tympanic membrane and to improve the hearing loss. AIM: To
      compare the two different techniques of myringoplasty- circumferential subannular
      grafting technique and conventional underlay technique in cases of chronic otitis
      media with inactive mucosal disease. MATERIALS AND METHODS: This is a prospective
      study of 12 months (July 2014 to June 2015) duration conducted in Department of
      Otorhinolaryngology and Head and Neck Surgery, JJM Medical College, Davanagere
      and data was collected from the 50 patients admitted for myringoplasty, 25 in
      each group. Results were calculated in terms of graft success rate and
      improvement in hearing after 3 months postoperatively. RESULTS: A total of 50
      cases are included in this study, out of which 21 were males and 29 were females
      with male to female ratio of 0.72:1. The success rate of graft take up by
      circumferential subannular grafting technique is 96% and by conventional underlay
      technique is 76% respectively. In circumferential subannular grafting technique,
      the pre-op mean PTA was 36.92db, and the post-op mean PTA after 3 months was
      25.87 db with a mean difference in PTA (dB) was 11.05 with t value of 7.74. In
      case of conventional underlay technique, the pre-op mean PTA was 38.24 db, and
      the post-op mean PTA after 3 months was 30.28 db with a mean difference in PTA
      (dB) was 7.96 with t-value of 14.39. CONCLUSION: The study showed that
      circumferential grafting technique is superior in graft success rate and
      postoperative hearing improvement when compared to conventional underlay
      technique.

PMID- 27042492
TI  - Congenital Atresia of Wharton's Duct.
AB  - This is a case report of a three-month-old male who presented to clinic with a
      cystic lesion under the tongue. On clinical examination, a cystic lesion was
      observed in the, floor-of-mouth. The patient was referred to Paediatric
      Otorhinolaryngology service for further management. The differential diagnoses
      for floor-of-mouth lesions should be reviewed with primary focus on the Wharton's
      duct atresia and its management. It is crucial to recognize submandibular duct
      atresia in the primary Paediatric clinic in order to expedite management of
      lesion before complications arise including infection, enlargement of cyst, and
      feeding and breathing difficulties. 

PMID- 27042493
TI  - Comparison of Long-term Complications in Patients on Haemodialysis and Peritoneal
      Dialysis Longer than 10 Years.
AB  - INTRODUCTION: Depending on developments in dialysis techniques and new treatment
      strategies for comorbid diseases, life expectancy has increased. As a result,
      dialysis related long term complications could be seen more frequently. We
      investigated and compared long term complications of the Haemodialysis (HD) and
      Peritoneal Dialysis (PD) in patients with history if either mode at least
      10years. MATERIALS AND METHODS: A 13HD & 16PD patients were included to the
      study. Basic demographic parameters and prevalence of cardiovascular diseases
      (CVD), uraemic peripheral neuropathy (PNP), parathyroid adenoma,
      parathyroidectomy and acquired cystic disease (ACD) were assessed. RESULTS: HD
      patients were older than PD patients (p=0.035) and duration of dialysis was
      longer in HD patients (p=0.001). CVD was present in 18 patients (9 HD, 9 PD).
      There was no difference in presence of CVD between HD and PD patients (p=0.455).
      Valvular diseases (n=15), diastolic dysfunction (n=8), left ventricular
      hypertrophy (n=5), ischemic heart disease (n=3) and congestive heart failure
      (n=1) were investigated. Uraemic peripheral neuropathy was observed in 14 of the
      patients (8 HD, 6 PD patients). Eight patients had mixed type sensory motor
      neuropathy and 3 patients had mixed type sensorial neuropathy, 2 patients had
      demyelinating PNP, 1 patient had axonal PNP and 3 of them had CTS related to
      peripheral neuropathy. Parathyroid adenoma was detected in 4 patients (2 HD, 2
      PD) and 3 patients (1 HD, 2 PD) had history of parathyroidectomy. Serum phosphate
      and iPTH levels were higher in HD patients (p=0.003, p=0.04, respectively). ACD
      was detected in 14 patients (7 HD, 7 PD). There was no difference between PD and
      HD patients (p=0.75). CONCLUSION: HD patients were older than PD patients and had
      longer duration of dialysis. The prevalence of long term complications was
      similar in HD and PD modalities. CVD especially valvular diseases were common
      complication in both modalities.

PMID- 27042494
TI  - Sleep Dysfunction in Parkinson's Disease.
AB  - INTRODUCTION: Sleep disorders are common in Parkinson's Disease (PD). It can
      antedate the motor manifestations of PD. It is related primarily to the
      involvement of sleep regulating structures, secondary involvement through motor,
      depressive and dysautonomic symptoms and the tertiary involvement through anti
      parkinsonian medications. AIM: The aim of our study is to evaluate the frequency
      and nature of the sleep abnormalities in Idiopathic Parkinson's Disease,
      analysing the sleep architecture using polysomnography and to correlate the
      results with the disease parameters. MATERIALS AND METHODS: A cross-sectional
      study was done in 50 patients who fulfill the "UK Parkinson's Disease Society
      Brain Bank Clinical Diagnostic Criteria". They were assessed using detailed
      history and clinical neurological examination. The severity of the disease was
      assessed based on Unified Parkinson's Disease Rating Scale (UPDRS part III) and
      the sleep is assessed using Parkinson's Disease Sleepiness Scale (PDSS) and
      Epworth Sleepiness Scale (ESS). Objective sleep study was done using
      polysomnography. RESULTS: Disturbed sleep was reported by 70% of patients. Sixty
      percent of them had difficulty in falling asleep and 48% had difficulty in
      maintaining the sleep due to frequent awakenings. Day time somnolence was
      reported by 30% of patients. Polysomnographic analysis showed reduced total sleep
      time in 40 patients (80%). Correlation analysis of the total sleep time, sleep
      efficiency, deep sleep time, REM sleep time with the disease duration, staging,
      severity, PDSS Score, showed significant positive correlation (p<0.05). Sleep
      related movement disorders like Periodic Limb Movements (PLMS), Restless Leg
      Syndrome (RLS) also showed inverse correlation with disease duration and severity
      (p<0.05). CONCLUSION: Sleep architecture is markedly disturbed in patients with
      Idiopathic Parkinson's disease. There is a reduction in the total sleep time,
      deep sleep time and REM Sleep duration. Periodic limb movements in sleep,
      restless leg syndrome, and obstructive sleep apnea contributes to the sleep
      fragmentation resulting in defective day time functioning.

PMID- 27042495
TI  - Predicting Healthcare Utilization by Patients Admitted for COPD Exacerbation.
AB  - BACKGROUND: Healthcare utilization, especially length of hospital stay and ICU
      admission, for acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD) determine overall outcomes in terms of morbidity, mortality and cost
      burden. Predicting prolonged hospital stay (PHS) and prolonged intensive care
      (PIC) for AECOPD is useful for rational allocation of resources in healthcare
      centres. AIM: To characterize the pattern of healthcare utilization by COPD
      patients hospitalized for acute exacerbation, and to identify clinical and
      laboratory predictors of 'prolonged hospital stay' (PHS) and 'prolonged intensive
      care'(PIC). MATERIALS AND METHODS: This study attempted through retrospective
      data analysis, to identify risk factors and evolve prediction models for
      increased healthcare utilization namely PHS and PIC for AECOPD. The data were
      extracted from 255 eligible admissions for AECOPD by 166 patients from Aug 2012
      to July 2013. Logistic regression analysis was used for identifying predictors
      and models were tested with area under receiver operating characteristic curve.
      RESULTS: Independent predictors of prolonged hospital stay (>= 6 days) were
      chronic respiratory failure at baseline, low saturation at admission, high HbA1c
      level and positive isolates in sputum culture. Independent predictors of
      prolonged intensive care (for >= 48 hours) were past history of pulmonary
      tuberculosis, chronic respiratory failure at baseline, low saturation at
      admission, high leukocyte count and positive culture isolates in sputum.
      Prediction models evolved from variables available at admission showed AUC 0.805
      (95% CI 0.729 - 0.881) and 0.825 (95% CI 0.75 - 0.90) for PHS and ICU admissions
      respectively. CONCLUSION: Our prediction models derived from simple and easily
      available variables show good discriminative properties in predicting PHS and PIC
      for AECOPD. When prospectively validated, these models are useful for rational
      allocation of services especially in resource limited settings.

PMID- 27042496
TI  - Effect of Heparin on Coagulation Tests: A Comparison of Continuous and Bolus
      Infusion in Haemodialysis Patients.
AB  - INTRODUCTION: Haemodialysis is one of the most conventional treatments of chronic
      renal failure. The risk of clot formation is high during haemodialysis due to
      regular contact of blood with the surfaces of foreign objects such as catheters,
      dialyzers' membrane, and other materials used for dialysis. Therefore, to prevent
      clot formation during haemodialysis, the dialysis system requires
      anticoagulation; this is usually done by heparin. AIM: The present study aimed to
      compare two heparinization methods and determine the proper impacts of these
      methods. MATERIALS AND METHODS: In this quasi-experimental study, 80
      haemodialysis patients covered by the dialysis center of Amir-al-momenin Hospital
      of Zabol were studied in two 40-member groups of heparin therapy methods of bolus
      injection and continuous infusion. PT and PTT were measured in blood samples
      collected from all patients before starting haemodialysis. The first group
      received 3000 units of heparin once the haemodialysis machine started to work and
      2000 units of heparin two hours later as bolus injection. In the second group,
      1500 units of heparin was injected at the start of dialysis after then, 5000
      units of heparin (one mL) were mixed with 11 mL of distilled water and infused
      using a heparin injection pump up to half an hour before the end of dialysis. At
      30 minutes after starting dialysis and at the end of 4 hours of haemodialysis, PT
      and PTT were measured and compared between the two groups. RESULTS: According to
      the results, the mean partial thromboplastin time in the bolus and continuous
      heparin-receiving group was 41.75+/-6.29 and 37.90+/-4.77, respectively, which
      was statistically significant (p=0.036). But PT was 14.45+/-1.82 in the bolus
      heparin group and 13.95+/-1.39 in the continuous heparin group, which was not
      significant according to the results of independent t-test (p=0.336). CONCLUSION:
      The results indicated a statistically significant difference between the bolus
      heparin injection and the continuous heparin infusion groups in terms of
      coagulation tests in haemodialysis patients (p=0.036). Therefore, given the
      effects of heparin on coagulation, it was more effective in the bolus heparin
      group than the continuous infusion group. It is recommended to use the bolus
      method for heparin therapy during haemodialysis.

PMID- 27042497
TI  - Study the Impact of Diabetes Camps on Adherence to Medication and Glycaemic
      Control in Uttarakhand.
AB  - INTRODUCTION: Diabetes is a major public health problem which needs to be
      addressed with outmost planning in resource poor settings. Good glycaemic control
      and medication adherence patterns can play an important role in reducing disease
      related complications thereby reducing morbidity and mortality among diabetics.
      Disease specific camps can act as a stepping stone in providing limited care to
      the patients. AIM: The study was planned to study the impact of diabetes camp on
      glycaemic control and adherence to antidiabetic medication among diabetic
      patients at a Government Teaching Hospital, Srinagar, Garhwal, Uttarakhand,
      India. MATERIALS AND METHODS: A cross-sectional study using a medication
      adherence questionnaire collected from the patients participating in diabetic
      camps and measuring their HbA1C levels before and after the camps along with
      spreading awareness about the disease. Two diabetes awareness camps were
      organized, three month apart and the participants were imparted knowledge about
      the disease. A total of 50 patients with type 2 DM who had self reported history
      of diabetes and were on some form of oral anti diabetics confirmed by their
      prescriptions. The patients were called for monthly follow up in outpatient
      department. A six question preformed questionnaire - the Girerd's instrument was
      used to assess the level of adherence to the prescribed anti-diabetic drugs in 50
      patients with type 2 diabetes mellitus, their HbA1C levels were estimated and the
      results were analysed using standard statistical methods. RESULTS: A total of 50
      type 2 diabetic, 48 were studied comprising 23 (47.9%) women and 25 (52.1%) men
      with a mean age of 57.43 years. The average duration of diabetes among
      participants was 7.02 years. Poor medication adherence score was recorded in 27
      participants and only 7 participants had good adherence to medication before the
      camp. After the camp, 19 participants had good adherence and 7 had poor
      medication adherence scores. As a result of improved adherence, improvement in
      glycaemic control was noticed by a decrease of 0.5 units in the mean HbA1C value
      by the end of the study. CONCLUSION: The results clearly showed that group
      intervention in the form of camp combined with monthly follow-ups could improve
      adherence as well as glycaemic control at a government teaching hospital in a
      resource poor setting. This could also involve and encourage society as well as
      young trainees to participate collectively in the care of diabetics.

PMID- 27042498
TI  - Uric Acid and Coronary Artery Disease, Two Sides of a Single Coin: A Determinant
      of Antioxidant System or a Factor in Metabolic Syndrome.
AB  - INTRODUCTION: Uric acid has antioxidant activity and it is expected to protect
      against coronary artery disease (CAD). Contradictory, it is a component of
      metabolic syndrome and so a risk factor for CAD. The associations of plasma total
      antioxidant capacity (TAOC) and uric acid (UA) as well as other risk factors were
      investigated relative to the occurrence and severity of CAD. MATERIALS AND
      METHODS: The study population consisted of 148 males and 152 females aged 35-76
      years who were classified as CAD cases and controls according to the results of
      coronary angiography. The severity of CAD was scored on the basis of the number
      and the extent of lesions at coronary arteries. The concentrations of UA and TAOC
      were measured by using of FRAP and enzymatic uricase methods. RESULTS: The
      prevalence of hypertension, cigarette smoking and diabetes mellitus was more
      frequent in CAD cases than controls. Patients with CAD when compared with the
      controls had increased levels of glucose, triglycerides, creatinine, UA, TAOC and
      decreased levels of HDL- cholesterol. Serum UA was high positive correlate of
      serum total and LDL-cholesterol, triglyceride, creatinine, BUN, bilirubin, TAOC
      and negative correlate of glucose and HDL-C. TAOC and its major determinant UA
      but not bilirubin and albumin are significantly associated with the prevalence
      and severity of CAD. In multivariate analysis and in the absence of hypertension,
      UA but not TAOC would remain and be associated with CAD by the OR of 1.57 (1.07
      2.29), p=0.02. If the results adjusted for all major risk factors including
      hypertension, neither TAOC nor UA would remain in the regression equation.
      CONCLUSION: The results suggest that TAOC and UA but not bilirubin and albumin
      are associated with CAD significantly. But, the correlation is not independent
      and is attributed to the metabolic syndrome. The measurement of UA and TAOC will
      not improve the prognostic power beyond the classical risk factors.

PMID- 27042499
TI  - Correlation of Endothelial Nitric Oxide Synthase Gene Polymorphism (GG, TT and GT
      Genotype) with Proteinuria and Retinopathy in Type 2 Diabetic Patients.
AB  - BACKGROUND: Nephropathy is the most important leading cause of end stage renal
      failure in type 2 diabetic patients, so numerous studies were done to diagnose
      and evaluate risk factors of diabetic nephropathy (DN). Some gene polymorphisms
      may be associated with progression or regression of DN, so the aim of this study
      was to compare prevalence of eNOS gene polymorphism in diabetic patients with
      controls and its association with diabetic nephropathy. MATERIALS AND METHODS: In
      a cross-sectional study, 94 type 2 diabetic patients and 94 normal participants
      were enrolled. Patients without retinopathy were excluded from this study. For
      all of the patients, fasting blood sugar (FBS), 2 hours post-prandial (BS), Blood
      Urea Nitrogen (BUN), Creatinine (Cr), 24 hours urine protein were measured in the
      case group. Endothelial nitric oxide synthetase gene polymorphism was evaluated
      in the case and control groups. RESULTS: There was no significant difference
      based on age and sex between patients in case and control groups. GG genotype of
      eNOS was less common in the patient group compared to control group. There was no
      difference between prevalence of TT, GT or GG genotype based on age and sex.
      There was no correlation between diabetic retinopathy or proteinuria and
      genotypes of eNOs. CONCLUSION: The study showed that in type 2 diabetic patients,
      NOS gene polymorphism was more common compared to normal population; however,
      there is no correlation between this gene polymorphism and proteinuria or
      retinopathy in these patients.

PMID- 27042500
TI  - Carpal Tunnel Syndrome in Hypothyroidism.
AB  - INTRODUCTION: Carpal Tunnel Syndrome (CTS) is an entrapment neuropathy that
      occurs due to compression of median nerve in the carpal tunnel and hypothyroidism
      is one of the important causes of CTS. AIM: To study clinical profile of carpal
      tunnel syndrome in patients with primary hypothyroidism. MATERIALS AND METHODS:
      This was cross-sectional study done in Smt. Kashibai Navale Medical College,
      Pune, Maharashtra. Adult patients with diagnosis of primary hypothyroidism were
      included in this study. Patients with other possible causes of CTS were excluded.
      Detailed medical history was obtained and all patients underwent clinical
      examination and nerve conduction study by electrophysiological method. RESULTS:
      Total 36 adult patients were included in this study, 86.1% females and 13.9%
      males. CTS were found in 6 (16.7%) patients. Increased Body Mass Index (BMI) and
      presence of clinical symptoms and/or signs of CTS correlated independently with
      presence of CTS in hypothyroidism. (p-value- 0.03 and < 0.0001 respectively). No
      correlation was found between gender, age of the patient, duration of disease,
      serum TSH level, aetiology of the disease, thyroid hormone replacement therapy
      and occurrence of CTS in hypothyroidism. CONCLUSION: Increase in BMI is an
      important risk factor for CTS in hypothyroidism and clinical evidence of CTS is a
      very sensitive parameter for the same.

PMID- 27042501
TI  - Unraveling the Mystery Behind A Patient with 'Refractory Seizures'.
AB  - Neurological manifestations such as seizures although rare are well recognized
      presentations of cardiac arrhythmias. Almost always, such events are primarily
      generalized in nature leading on to loss of consciousness. Rarely however,
      cardiac seizures can manifest with focal neurological events. We report a case of
      a sexagenarian who presented with recurrent focal seizures with secondary
      generalization, who was misdiagnosed and treated as seizure disorder; only a
      careful history and focussed investigations helped in realising a precise
      diagnosis. 

PMID- 27042502
TI  - Primary Spindle Cell Malignant Melanoma of Esophagus: An Unusual Finding.
AB  - Malignant melanoma of esophagus is usually a metastatic tumour rather than a
      primary tumour. Primary malignant melanoma accounts for less than 0.2% of all
      esophageal neoplasm. We report a case of primary spindle cell malignant melanoma
      of esophagus in a 69-year-old male who presented with history of dysphagia since
      1 month. Radiological examinations revealed polypoidal growth at lateral aspect
      of esophagus. Biopsy was reported as grade III squamous cell carcinoma. Video
      assisted thoracoscopic esophagectomy was performed. Histopathological examination
      along with immunohistochemistry gave confirmed diagnosis of primary spindle cell
      malignant melanoma of esophagus. Though a rare entity, due to its aggressive
      nature and poor prognosis primary malignant melanoma should be one of the
      differential diagnoses in a patient with polypoidal esophageal mass lesion.
      Despite radical surgical treatment prognosis is extremely poor. 

PMID- 27042503
TI  - Exchange Transfusion in Severe Falciparum Malaria.
AB  - Malaria is endemic in India with the incidence of P. falciparum Malaria
      increasing gradually over the last decade. Severe malaria is an acute disease,
      caused by P. falciparum, but increasingly also by P. vivax with major signs of
      organ dysfunction and/or high levels of parasitaemia (>10%) in blood smear. Use
      of exchange transfusion with antimalarial drug therapy as an additional modality
      of treatment in severe Falciparum malaria is controversial and is unclear. We
      report a case of severe malaria complicated by multiorgan failure and ARDS.
      Patient responded well to manual exchange transfusion with standard artesunate
      based chemotherapy. 

PMID- 27042504
TI  - Hajdu Cheney Syndrome.
AB  - Hajdu-Cheney Syndrome is a rare genetic disorder characterised by progressive
      focal bone destruction. It is known to be an autosomal dominant disorder but
      there have been reports of sporadic cases as well. Although the disease
      manifestation is found to begin from birth, it is most often not diagnosed until
      adolescence or adulthood. It could be due to the rarity of the condition and the
      variation of the disease manifestation at different age groups. We report a case
      of Hajdu-Cheney Syndrome in a 26-year-old male who presented with severe
      periodontitis and premature loss of teeth. The other characteristic features
      included craniofacial dysmorphism, abnormalities of the digits and dental
      anomalies. Patients with craniofacial dysmorphism along with dental abnormalities
      should be thoroughly examined for any underlying systemic disorder. A team of
      specialists may be able to diagnose this condition before the disease is
      advanced. 

PMID- 27042505
TI  - Paraquat Poisoning: A Case Report.
AB  - Paraquat is commonly used herbicide by farmers in North West Rajasthan. Despite
      its easy availability, poisoning of its not common. Fatal dose of paraquat is so
      small that >10 ml poison can damage lungs permanently. Diagnosis is often
      difficult without proper history, absence of specific clinical feature and lack
      of diagnostic test. Inhalation exposures represent one of the most important
      routes of poisoning. We are reporting a case of inhaled paraquat poisoning with
      complication of irreversible acute kidney, liver and lung injury. 

PMID- 27042506
TI  - Fever with Rash, an Alarm to the Physicians - A Case Report of Atypical Measles.
AB  - Measles is a highly contagious disease caused by Paramyxovirus group. It has been
      estimated that globally deaths occurs out of measles. The disease still remains
      as one of the leading cause of death among young children and adults despite the
      effective vaccination. The outbreak of measles is on rise in recent years with
      serologically confirmed cases in India. The incidence and complications of
      atypical measles is usually severe among older age groups even prior
      immunization. We report a case of 15-year-old male with symptoms of fever and
      rash with possible differential diagnosis and emphasize on the clinical
      presentation of atypical measles among adolescent age group with an additional
      evidence of investigations. 

PMID- 27042507
TI  - Necessity is the Mother of Invention.
AB  - A well executed transseptal puncture is crucial for successful percutaneous
      transvenous mitral balloon valvotomy. We report a case of accidentally damaged
      Mullins sheath dilator. Due to immediate unavailability of another dilator at
      cardiac catheterization laboratory, angioplasty guidewire and balloon was used as
      an additional assisting armamentarium for successful percutaneous transvenous
      mitral balloon valvotomy. 

PMID- 27042508
TI  - Acute Myoclonic Jerk Terminated by A Simple Procedure - A Case Report.
AB  - Myoclonic jerks are brief involuntary twitching of a muscle or a group of
      muscles. It is a medical sign and not a diagnosis of a disease. It occurs in
      number of secondary conditions like hepatic failure, renal failure,
      dyselectrolytaemia, etc in addition to the physiologic, epileptic, essential and
      psychogenic causes. Myoclonic jerks secondary to uraemia usually occur in the end
      stage renal failure and is resolved by renal replacement therapy. Here we report
      a case of uremic myoclonic jerk presented to our emergency department which
      occurred secondary to obstructive uropathy secondary to neurogenic bladder caused
      by old traumatic paraparesis and it was resolved by simple and timely
      intervention by bladder catheterization and it prevented the patient from going
      into uremic encephalopathy. 

PMID- 27042509
TI  - Japanese Encephalitis Complicated with Obstructive Hydrocephalus.
AB  - Japanese Encephalitis (JE), caused by Japanese encephalitis virus (JEV), a flavi
      virus, is the most significant aetiology of arboviral encephalitis worldwide. It
      has resulted in epidemics of encephalitis in the Indian subcontinent. Here, we
      report a case of 36-year-old female who presented with a short history of fever
      and headache followed by altered sensorium. Funduscopic examination revealed
      Papilloedema. Pyogenic or viral meningoencephalitis along with complicated
      malaria were kept as initial differential diagnosis. Magnetic Resonance Imaging
      (MRI) of brain revealed involvement of posterior limb of internal capsule and
      bilateral thalami in the form of haemorrhagic encephalitis along with obstructive
      hydrocephalus. Cerebro Spinal Fluid (CSF) serology (IgM ELISA) showed JE as the
      causative agent. Despite extensive literature search, we could not find a case of
      JE reported with hydrocephalus as a complication. This case highlights the
      typical and atypical features of JE including imaging findings and exemplifies
      the way, how diversely JE can present and would thus help in preparing management
      paradigms accordingly. 

PMID- 27042510
TI  - Gullo's Syndrome: A Case Report.
AB  - Benign Pancreatic Hyperenzymemia (BPH) or Gullo's Syndrome is a new entity with
      only few reported cases till date. It is characterized by persistently elevated
      pancreatic enzymes without any clinical or pathological evidence of pancreatic
      disease. Gullo's syndrome is a diagnosis of exclusion and clinician should be
      aware of various other conditions which can cause elevation of pancreatic
      enzymes. There are no reported cases of Gullo's syndrome from Indian subcontinent
      till date. A 42-year-old lady presented to us with complaints of fever and cough
      for which she was evaluated and diagnosed to be having left upper zone pneumonia.
      However, her routine investigations showed persistently elevated serum amylase
      and lipase levels. She was extensively worked up for pancreatic hyperenzymemia
      but no pancreatic disease was detected. She was followed up for a period of one
      year and raised levels of serum lipase and amylase persisted even after a year. 

PMID- 27042511
TI  - "Petrified Ears" in Secondary Adrenal Insufficiency.
AB  - Petrification of the auricle, a rarely encountered clinical entity usually
      results from ectopic calcification of the auricular cartilages and manifests as
      rigid ear. The underlying pathogenesis remains ambiguous with several proposed
      hypotheses till date. Auricular calcification may be the sole cutaneous marker of
      underlying endocrinopathy at times. Adrenal insufficiency is the most common
      endocrinological disorder to be associated with such stiff ears and it has been
      described in both primary as well as secondary forms of the disease. We present
      here a 30-year-old man whose clinical condition deteriorated following
      levothyroxine supplementation and the presence of "petrified ears" ultimately
      provided a clue to the diagnosis of associated secondary adrenal insufficiency. 

PMID- 27042512
TI  - Vasculitis as a Presenting Manifestation of Chronic Hepatitis B Virus Infection:
      A Case Report.
AB  - Hepatitis B virus is responsible for causing hepatic complications like acute and
      chronic hepatitis, cirrhosis and hepatocellular carcinoma along with some
      uncommon immune mediated extrahepatic manifestations. Vasculitis remains an
      uncommon extrahepatic complication of hepatitis B virus infection. Herein we
      report a case of hepatitis B infection that presented with leucocytoclastic
      vasculitis as an initial manifestation and managed successfully with entacavir
      therapy. 

PMID- 27042513
TI  - Hammer in the Heart on Coronary Angiography.

PMID- 27042514
TI  - Effect of Dissection of the Recurrent Laryngeal Nerves on Parathyroid
      Insufficiency during Total Thyroidectomy for Multinodular Goitre.
AB  - INTRODUCTION: Total thyroidectomy is the accepted standard treatment for benign
      goitrous enlargements. The surgical skill and technique is one of the most
      important factor which affect the outcome in thyroid surgery. Hypocalcaemia due
      to parathyroid insufficiency remains a significant postoperative morbidity after
      total thyroidectomy. The primary cause is unintentional damage to, or
      devascularization of, one or more parathyroid glands during surgery. AIM: To
      study the risk of hypocalcaemia due to recurrent laryngeal nerves (RLNs)
      dissection during total thyroidectomy for benign multinodular goitre (MNG).
      MATERIALS AND METHODS: The study is a non-randomized control trial, where 100
      patients with benign MNG were divided into two groups (group A and group B) each
      consisting of 50 patients. All 100 patients underwent total thyroidectomy by a
      subcapsular dissection. In patients of group A, both RLNs were clearly dissected
      for a minimum length of 2cm down from its entry into the larynx before total
      thyroidectomy was performed. In group B, each patient had total thyroidectomy
      without making any deliberate attempt to dissect and demonstrate the RLNs. The
      patients in the two groups were followed up for the incidence of clinically
      significant hypocalcaemia in the postoperative period. RESULTS: A total of 30% of
      patients in group A developed clinical and biochemical manifestations of
      hypocalcaemia but the incidence of hypocalcaemia was only 6% in the group B.
      Three (6%) patients out of those who developed hypocalcaemia in group A had a
      prolonged hypocalcaemia for upto six months. p-value is 0.003 and odds ratio is
      6.59. CONCLUSION: Routine dissection to identify the RLNs could predispose to a
      higher incidence of postop hypocalcaemia. Subcapsular dissection of the thyroid
      safely preserves the parathyroid glands.

PMID- 27042515
TI  - Metabolic Evaluation in Paediatric Urolithiasis: A 4-Year Open Prospective Study.
AB  - INTRODUCTION: Children with urolithiasis are associated with considerable
      morbidity and commonly associated with metabolic abnormalities. By treating these
      abnormalities stone formation is prevented. OBJECTIVES: To study the metabolic
      risk factors of urolithiasis in children and compare them with literature.
      MATERIALS AND METHODS: In open, prospective and observational study, 75 children
      were evaluated from August 2010 to June 2014. In all patients' dietary history,
      water intake and results of laboratory findings were recorded. All urine samples
      obtained from patients were without dietary restrictions. Reference paediatric 24
      hour urinary parameter was used according to western literature. RESULTS: We
      investigated 75 patients with urolithiasis. Low urine volume was found in 49
      patients which is comparable with previous studies indicating simple intervention
      as to increase water intake. Low calcium intake was found in 44 patients
      suggesting that low calcium intake is associated with higher incidence of
      urolithiasis due to increased intestinal oxalate absorption. Hypocalcaemia was
      found in 32 patients and 24 hour urinary abnormality was found in only 16
      patients'. Both these finding does not support previous literature. Stone
      analysis finding does not correlate with urinary finding. CONCLUSIONS: Low urine
      volume secondary to low water intake is predominant finding. Hypocalcaemia is
      major metabolic abnormality in contradiction to western literature. There are no
      nomograms for urinary excretion of Calcium, uric acid, oxalate and citrate in
      Indian children. Keeping the optimum blood calcium level & increased fluid intake
      can prevent stone formation in children.

PMID- 27042516
TI  - Profile of Breast Diseases in Post Pubertal Women Assessed By Clinical Breast
      Examination - A Community Based Study in Rural Pondicherry.
AB  - INTRODUCTION: Breast diseases in women, whether benign or malignant, are very
      commonly encountered. Benign diseases are under reported and cancer is one of the
      leading causes of mortality in women. This study was undertaken with an aim to
      study the profile of various breast disease in the community. MATERIALS AND
      METHODS: In this observational study all the post pubertal women residing in the
      selected village (n=1000) were included. The study was done from September 2013
      to August 2015. A thorough history taking was done with the help of a predesigned
      proforma followed by a clinical breast examination and further investigation at
      our hospital if necessary. RESULTS: It was found in this study that mastalgia,
      both cyclical and non-cyclical as well as lumps were a common finding in the
      general population. Significant proportions of women were found to be in the peri
      menopausal age group. Median age of menarche was 13 years; menopause was 45
      years. The average age at first childbirth was 21 years with 1 year being the
      median duration of breast-feeding. A total of 128 women (1 in 8) had positive
      symptomatology with 94 (1 in 11) of them having a breast disease on examination.
      One was diagnosed with breast cancer. The prevalence of cyclical mastalgia was 1
      in 11, non-cyclical mastalgia 1 in 34, fibroadenosis 1 in 23 and fibroadenoma 1
      in 100. The awareness regarding risk factors and the availability of screening
      program was very poor. The average age of presentation of mastalgia was 34 years;
      fibroadenosis was 35 years and fibroadenoma 29 years. None of the women
      interacted with or had consulted a practitioner regarding mastalgia as it was not
      perceived to be a sign of malignancy and did not cause any significant
      discomfort. CONCLUSION: It was thus concluded from this study that benign breast
      diseases are a common occurrence in the general population. Breast cancer
      continues to be diagnosed only at later stages owing to lack of awareness and
      inadequately structured screening program. The concept of self-breast examination
      seems to be poorly understood. CBE is more fruitful with subsequent radiological
      and histopathological investigation, if warranted.

PMID- 27042517
TI  - Lichtenstein Mesh Repair (LMR) v/s Modified Bassini's Repair (MBR) + Lichtenstein
      Mesh Repair of Direct Inguinal Hernias in Rural Population - A Comparative Study.
AB  - INTRODUCTION: Lichtenstein's tension free mesh hernioplasty is the commonly done
      open technique for inguinal hernias. As our hospital is in rural area, majority
      of patients are labourers, open hernias are commonly done. The present study was
      done by comparing Lichtenstein Mesh Repair (LMR) v/s Modified Bassini's repair
      (MBR) + Lichtenstein mesh repair (LMR) of direct Inguinal Hernias to compare the
      technique of both surgeries and its outcome like postoperative complications and
      recurrence rate. MATERIALS AND METHODS: A comparative randomized study was
      conducted on patients reporting to MNR hospital, sangareddy with direct inguinal
      hernias. A total of fifty consecutive patients were included in this study of
      which, 25 patients were operated by LMR and 25 patients were operated by MBR+LMR
      and followed up for a period of two years. The outcomes of the both techniques
      were compared. RESULTS: Study involved 25 each of Lichtenstein's mesh repair
      (LMR) and modified bassini's repair (MBR) + LMR, over a period of 2 years. The
      duration of surgery for lichtenstein mesh repair is around 34.56 min compared to
      LMR+MBR, which is 47.56 min which was statistically significant (p-value is
      <0.0001). In this study the most common complication for both the groups was
      seroma. The pain was relatively higher in LMR+MBR group in POD 1, but not
      statistically significant (p-value is 0.0949) and from POD 7 the pain was almost
      similar in both groups. The recurrence rate is 2% for LMR and 0% for MBR+LMR.
      CONCLUSION: LMR+MBR was comparatively better than only LMR in all direct inguinal
      hernias because of low recurrence rate (0%) and low postoperative complications,
      which showed in our present study.

PMID- 27042518
TI  - Outcome and Predicting Factor Following Severe Traumatic Brain Injury: A
      Retrospective Cross-Sectional Study.
AB  - INTRODUCTION: Severe traumatic brain injury (TBI) is a major and challenging
      problem in critical care medicine. AIM: To assess the outcome and predicting
      factor following severe TBI. MATERIALS AND METHODS: This is a retrospective and
      cross-sectional study. Data were collected from two sections; one section
      consisting of a questionnaire answered by the patients and other section from the
      patient records. The instruments used included the Glasgow Outcome Scale (GOS),
      SF-36 and the Hospital Anxiety and Depression Scale (HAD). RESULTS: The mortality
      rate of the patients was 46.2%. The quality of life (QOL) of the patients in most
      dimension were impaired and (58%) of patients had unfavourable QOL. About (37.5%)
      of patients with anxiety and (27.5%) had a depression. A significant correlation
      was found between age, GCS arrival, length of ICU stay, mechanical ventilation,
      VAP & ARDS and pupil reactivity with QOL, GOS, HAD-A and HAD-D (p<0.05, p<
      0.001). GCS arrival a predicate factor for QOL and GOS (p <0.001, OR: 1.75, 1.94
      respectively); length of ICU stay a predicate factor for QOL and GOS (p <0.05, OR
      : 1.11, 1.28 respectively); mechanical ventilation a predicate factor for GOS (p
      <0.001, OR : 1.78); ventilation associated pneumonia (VAP) & acute respiratory
      distress syndrome (ARDS) and pupil reactivity a predicate factor for GOS (p
      <0.05, OR : 1.36; p<0.001, OR: 1.94 respectively). The GCS arrival and ICU stay a
      predicate factor for HAD-A (p<0.05, OR: 1.73, 1.38 respectively). CONCLUSION:
      With respect to results advanced in pre hospital, medical and surgical care for
      the decrease in mortality rates of Head trauma (HT), the use of trauma triage
      tools and strict enforcement of traffic rules are necessary.

PMID- 27042519
TI  - Role of Amylase and Lipase Levels in Diagnosis of Blunt Trauma Abdomen.
AB  - INTRODUCTION: Blunt Trauma Abdomen (BTA) is the leading cause of morbidity and
      mortality amongst all age groups. Spectrum of injury may vary from simple to life
      threatening multi organ involvement and therefore proper assessment and diagnosis
      becomes very important. AIM: To evaluate the role of serum amylase and lipase in
      diagnosis of blunt trauma abdomen. MATERIALS AND METHODS: This study was done on
      50 patients with diagnosis of BTA admitted in Dayanand Medical College and
      Hospital, Ludhiana. Serum amylase and lipase levels were estimated on days 1, 3
      and 5 of admission. RESULTS: Road side accident was the most common aetiology
      accounting for 40 patients. Thirty one patients were less than 35 years of age
      and 42 patients were males. Abdominal tenderness was the most common per abdomen
      finding, found in 31 patients, followed by distension, found in 21 patients. The
      most common organ injured was liver, seen in 27 patients. Fifteen patients
      underwent laparotomy while 35 patients were managed conservatively. There was
      statistically significant rise in serum amylase levels on days 1, 3 and 5 in
      patients with small and large intestinal injury. There was statistically
      significant rise in serum lipase levels on days 1, 3 and 5 in patients with
      stomach injury. Raised levels of serum amylase and lipase had a statistically
      significant prediction for the need of surgery in these patients. CONCLUSION:
      Serum amylase and lipase levels, when coupled with other laboratory tests and
      imaging modalities, may have significant role in predicting the site of injury as
      well as the surgical outcome in patients of BTA.

PMID- 27042520
TI  - An Unusual ST Elevation in a Case of Left Atrial Myxoma.
AB  - Myxomas are the most common and potentially dangerous benign tumours of the
      heart. They may have either smooth or papillary surfaces and may have thrombus
      adherent. As both the papillary excrescences and the surface thrombi are friable
      in nature hence may undergo embolization. We report a case of left atrial myxoma,
      which underwent excision of the tumour for mitral valve obstructive features. In
      the immediate postoperative period patient developed ST elevation in lead II, III
      and aVF. Coronary angiogram revealed normal coronary pattern. Patient was treated
      with aspirin, heparin and IABP for 48 hours and recovered well. We conclude that
      there is a tendency for spontaneous recanalization of the obstructed coronary
      vessels by tumour emboli, hence patient can be managed conservatively. 

PMID- 27042521
TI  - Acute Exercise-Induced Compartment Syndrome of the Leg- Don't Miss It.
AB  - Acute exercise induced compartment syndrome of leg is a very rare and very
      oftenly missed entity which leads to delay in its management. We are presenting
      such case in which diagnosis was established two days after the onset of
      symptoms. Urgent decompressive fasciotomy was done. After 3 months of follow up,
      patient has got full functional recovery of his affected limb. This case
      highlights the importance of keeping high index of clinical suspicion to diagnose
      the problem and manage promptly. We have reviewed the English literature and
      found only about 40 cases since 1945. 

PMID- 27042522
TI  - Purple Urine Bag Syndrome- An Alarming Situation.
AB  - Purple urine bag syndrome (PUBS) is an uncommon condition that occurs mainly in
      chronically catheterized patient and associated with urinary tract infection. It
      is characterised by purple discolouration of urine bag which leads to significant
      stress and anxiety to patient, care takers and health workers, so awareness
      regarding this condition is of utmost importance. In our report, an old gentleman
      with Benign Prostate Hyperplasia (BPH) on per urethral catheter (PUC) with past
      history of recurrent urinary tract infection developed burning micturition of
      urine with purple discoloration of urine bag. After proper antibiotic and
      catheter changed, discoloration subsided. In India, as life expectancy and
      geriatric care is improving, more patients are on PUC for various diseases. So,
      the incidence of PUBS will increase and awareness is required about the condition
      and its management. 

PMID- 27042523
TI  - Left Sided Appendicitis: Once Burned Twice Shy.
AB  - Acute appendicitis is one of the most common surgical conditions that are
      diagnosed in children presenting with acute abdominal pain in the emergency
      department. An atypical presentation of symptoms is encountered in 30% of cases.
      Atypical localization of the appendix as in left sided appendicitis, although
      rare, has an increased risk of missed or delayed diagnosis. We present two
      consecutive cases of left sided appendicitis in order to describe how increased
      awareness in the second case helped us to avoid pitfalls in the management and
      diagnosis of this atypical and variant condition. Increased cautiousness and
      awareness of left sided appendicitis can assist emergency physicians to avoid
      pitfalls in the management and diagnosis of this atypical and variant condition. 

PMID- 27042524
TI  - Gastric Trichobezoar with Rapunzel Syndrome: A Case Report.
AB  - Bezoars are collections of non-digestible matter that usually accumulates in
      stomach and can extend to small bowel. Trichobezoars (concretions of hair) are
      unusual and are usually found in young psychiatric females, who often deny eating
      their own hair (trichophagy). We are presenting a case of gastric trichobezoar
      with a long thin tail in a 20 years young female with a history of trichophagia.
      Patient was managed by exploratory laparotomy and anterior gastrotomy.
      Postoperatively she recovered well and was discharged in satisfactory condition
      with advice for psychiatric follow-up. 

PMID- 27042525
TI  - Bladder Endometriosis Mimicking TCC - A Case Report.
AB  - Endometriosis is the ectopic presence of endometrial tissue outside the uterus.
      Though on its own endometriosis is not a rare lesion, the involvement of the
      urinary tract is rare but with the bladder being the most commonly affected
      organ. Endometriosis is usually seen in females between the ages of 30-40 years
      and may occur due to fluctuating levels of oestrogen and progesterone. Clinically
      the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or
      heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been
      suggested that ultrasonography should be done either before or during
      menstruation as the lesion becomes more evident and a biopsy taken during this
      period is a strong aid in reaching a final diagnosis. We report here an unusual
      case of bladder endometriosis where the patient came with severe pelvic pain and
      an endoluminal mass seen on the ultrasonographic report. Based on these findings
      a differential of transitional cell carcinoma was given which was ruled out based
      on the cystoscopic findings. 

PMID- 27042526
TI  - Paget's Disease of Nipple in Male Breast with Cancer.
AB  - Carcinoma of the male breast accounts for less than 0.5% of all cases of breast
      cancer. However, Paget's disease of nipple in male is extremely rare. We report
      on a case of Paget's disease of nipple with breast cancer in a 51-year-old
      gentleman. He presented with a ulcerative lesion and lump in the left breast
      beneath the nipple-areolar region with single mobile ipsilateral central group of
      axillary nodes. Modified radical mastectomy was performed. On follow up, patient
      was doing well with no recurrence. 

PMID- 27042527
TI  - Mixed Germ Cell Tumour in an Infertile Male Having Unilateral Cryptorchidism: A
      Rare Case Report.
AB  - Mixed germ cell tumours with multiple components occur more frequently than the
      pure varieties of germ cell tumours. Embryonal carcinoma and teratoma together
      form the most common components of the mixed germ cell tumour but the yolk sac
      tumour is usually seen as a minor component in patients presenting with mixed
      germ cell tumour. We report a rare case of 27-year-old Hepatitis C positive male
      presenting with pain in left lower abdomen with associated history of same sided
      undescended testis and infertility. Right sided testis lying in scrotal sac
      appeared normal on ultrasonography but patient was azoospermic. He had raised
      levels of serum markers, alpha feto protein and beta HCG. Examination showed a
      large mass in left lower abdomen involving the sigmoid colon with the absence of
      left testis in left scrotum which was confirmed on CT scan. Excision of the mass
      was done and histopathology examination revealed it as a malignant mixed germ
      cell tumour composed predominantly of a yolk sac tumour, with minor component as
      seminoma and embryonal carcinoma in an undescended testis. Following this, the
      level of serum markers came down. The patient is now undergoing adjuvant
      chemotherapy and is doing well. 

PMID- 27042528
TI  - Malignant Proliferative Trichilemmal Tumour of The Nape of The Neck - A Case
      Report.
AB  - Proliferating trichilemmal tumours are benign but locally aggressive tumours
      arising from the hair follicle. They are biologically benign lesions, but may be
      locally aggressive. They are generally solitary lesion and commonly occurring in
      the scalp of elderly women. Malignant transformation has been known to occur but
      very rarely. Here we report a rare case of a recurrent malignant trichilemmal
      tumour of the scalp in a middle aged male which was surgically excised. 

PMID- 27042529
TI  - Hydrocele of the Canal of Nuck (Female Hydrocele): A Rare Differential for
      Inguino-Labial Swelling.
AB  - The inguinal canal is traversed by the spermatic cord in men and the round
      ligament of uterus in women. The round ligament is attached to the uterine cornu
      near the origin of fallopian tube at one end and to the ipsilateral labia majora
      at the other. The round ligament accompanies a pouch of parietal peritoneum in
      the inguinal canal, which is known as 'canal of nuck'. It is analogous to the
      processus vaginalis in males. Incomplete obliteration of the peritoneal pouch
      causes indirect inguinal hernia or hydrocele of the canal of nuck; a very rare
      condition in women. As these types of cases are rarely seen in surgical practice
      we present a case of such little-known developmental disorder in a three-year-old
      girl. She presented with irreducible, tender right inguino-labial swelling with
      tachycardia simulating incarcerated inguinal hernia, which necessitates emergency
      surgical exploration. On exploration it was found to be an encysted hydrocele of
      canal of nuck; so although rare, this entity should be considered in differential
      diagnosis in a female child presented with inguino-labial swelling. 

PMID- 27042530
TI  - Schwannoma of the Submandibular Gland: A Rare Case Report.
AB  - Schwannoma is a slow growing, benign, encapsulated tumour of Schwann cells, which
      form myelin in peripheral nerves. It is the most common tumour of peripheral
      nerve, also known as neurilemoma or neurimoma. Schawannomas of head and neck area
      is common and may arise from peripheral, central or autonomic nerve but Salivary
      gland schwannomas are rare extracranial forms. We report a rare case of
      schawannoma of submandibular gland which presented with painless swelling in
      submandibular region, treated by total excision of submandibular gland. There was
      no postoperative nerve deficit or recurrence within 9 months of follow up. 

PMID- 27042531
TI  - Ingested Sharp Bone Fragment: An Unusual Cause of Acute Bowel Obstruction- Case
      Report.
AB  - Acute bowel obstruction due to ingested foreign body (FB) like sharp bone
      fragment is a rare entity. As preoperative diagnosis was uncertain due to lack of
      proper history, diagnosis is usually done intraoperatively. Even though it is
      rare, we should consider it as differential diagnosis in patients with recent
      dietary history. Herein, we are reporting a 38-year-old man, without any
      psychiatric illness or previous surgery presenting to emergency department with
      the features of acute bowel obstruction. CT scan shows high density object in
      ileum suspicious of foreign body. Patient underwent exploratory laparatomy which
      reveals dilated small bowel with sharp bony object in ileum, which was retrieved
      with enterotomy. 

PMID- 27042532
TI  - An Interesting Case of Non-Resolving Hepatogastric Fistula - An Unseen Cause.
AB  - Hepatic tuberculosis presents one of the rare forms of extra-pulmonary
      tuberculosis. It is usually secondary to infection in the lung or the gut.
      Tuberculous liver abscess is the rarer manifestation even in endemic areas of
      Mycobacterium tuberculosis. Hepatogastric fistula secondary to tuberculous liver
      abscess has never been reported in literature. We herein report a case of a
      disseminated tuberculous liver abscess complicated by hepatogastric fistula,
      which posed a considerable diagnostic challenge. It was treated successfully with
      anti tubercular drugs. Liver abscess with atypical features and non responsive to
      antibiotics should raise the suspicious of tuberculosis or fungal infections. 

PMID- 27042533
TI  - A Case Report of Chorea Associated with Hyperthyroidism.

PMID- 27042534
TI  - A Study of Tubal Recanalization in Era of ART (Assisted Reproduction Technology).
AB  - INTRODUCTION: Tubectomy remains one of the most popular methods of permanent
      contraception in developing countries. But about 10% of them regret their
      decision and 1% want to restore their fertility. Out of many options open method
      of tubal recanalisation is one of the method of restoring fertility. AIM: Primary
      objective was to analyse whether open tubal recanalization is a feasible option
      for those planning to conceive after tubectomy. Secondary objective was to
      evaluate the pregnancy rate and analyse the various factors affecting pregnancy
      rate after tubal recanalization. MATERIALS AND METHODS: A prospective study,
      follow-up of 2 year in patients treated with tubal recanalization during 2012
      2013 at tertiary teaching hospital. 10 women underwent tubal recanalization
      procedure. Open surgery was done and the principles of microsurgery were followed
      meticulously throughout the procedure. STATISTICAL ANALYSIS: All statistical
      analyses were performed using SPSS for Windows version 17.0 (SPSS Inc., Chicago,
      IL, USA). Data were expressed as means, medians, standard deviations, and
      percentages. We used Student's t-test to compare group means and Fisher-exact
      test to compare proportions. A p-value of <0.05 was considered significant.
      RESULTS: Out of 10 women who went recanalization an overall 50% pregnancy rate
      was achieved. All pregnancies occurred within 1 year of procedure. When previous
      sterilisation was done by laparoscopic route, after reversal all of them (100%)
      conceived while in those sterilised by Pomeroys method the pregnancy rate after
      reversal was only 16.6%. Following reversal pregnancy was stastically more
      significant in those with final tubal length of >5cm (p=0.04) and in those with
      Isthmo-Isthmic type of anastomosis . CONCLUSION: Open tubal recanalisation
      remains a feasible option for those planning pregnancy after tubectomy. The
      important factors for determining the success of operation were age of the
      patient, time interval between sterilization and reversal, site of ligation,
      method used for previous ligation and the remaining length of the tube after
      recanalisation.

PMID- 27042535
TI  - Open Versus Closed Laparoscopy: Yet an Unresolved Controversy.
AB  - INTRODUCTION: Safe placement of the Verres needle or the primary trocar for
      establishment of pneumoperitoneum is the most critical step in laparoscopic
      procedure as it is associated with bowel, bladder and life threatening vascular
      injuries and embolism. In the last few decades many techniques and guidelines
      have been introduced to eliminate complications in creation of pneumoperitoneum.
      Classical closed technique (Verres needle) and the open classic technique
      (Hasson) are the most commonly used techniques for creation of pneumoperitoneum.
      AIM: To compare the rate of occurrence and nature of complications in open and
      closed laparoscopy during establishment of pneumoperitoneum in different surgical
      and gynaecological procedures. MATERIALS AND METHODS: This was a comparative
      study conducted at three hospitals in Dibrugarh district, Assam, India from
      January 2012 to December 2014. Total 3000 cases were included in the study with
      1500 cases of open laparoscopy and 1500 cases of closed laparoscopy.
      Complications occurring in both the groups were compared by using Fisher's-exact
      test. RESULTS: In closed laparoscopy group minor complications occurred in 80
      (5.33%) and major complications in 20 (1.33%) cases. In open laparoscopy group
      minor complications were observed in 60 (4%) and major complications in 2
      (0.13%). The p-value of the difference between the two groups for minor
      complications was 0.0834 and for major complications was 0.0001(significant).
      CONCLUSION: Open laparoscopy was seen to be better than closed laparoscopy in
      terms of not only the rate of occurrence of complications but also the nature and
      severity of the complications. This study is clinically relevant as there is no
      consensus for a particular method of safe entry in to the peritoneal cavity
      warranting the need for more research. Open technique can be performed in all
      cases irrespective of previous operative scar, suspected intra peritoneal
      adhesions or obesity. Favourable outcome may be achieved in closed technique in
      cases of normal BMI, absence of postoperative scar in the abdomen, absence of
      abdominal and genital tuberculosis and pelvic inflammatory disease.

PMID- 27042536
TI  - Forgotten Vaginal Foreign Body Presenting as Cervical Dystocia.
AB  - Generally encountered in paediatrics age group, vaginal foreign body is a rare
      presentation in gynaecological clinics. Inserted as a part of sexual abuse,
      gratification or psychiatric disorder, these foreign bodies can present with a
      varied symptomatology. We report a case of 22-year-old female, a victim of
      domestic violence, who had a foreign body inserted in the vagina which was
      forgotten. Later it was discovered when she presented at term with cervical
      dystocia. 

PMID- 27042537
TI  - Ovarian Vein Thrombosis Presenting as Acute Abdomen in Puerperium.
AB  - Postpartum Ovarian Vein Thrombosis (POVT) is a rare, but serious condition that
      causes slow quadrant pain in the postpartum period. POVT must be considered in
      the differential diagnosis of postpartum acute abdomen. We hereby report a case
      on a 36-year-old Italian woman who developed an acute abdomen a week after
      spontaneous vaginal delivery. She had persistent fever and constipation.
      Diagnosis of POVT was made with an abdominal Computed Tomography (CT) and
      treatment with heparin and broad-spectrum antibiotics were started. After 72
      hours, the patient was switched from low molecular weight heparin to oral
      anticoagulant treatment. After 5 months a complete recanalization was
      demonstrated by abdomen CT and the treatment was stopped 6 months after
      diagnosis. POVT is a diagnosis of exclusion in the puerperium. This case
      illustrated that POVT may also occur in low risk patient. 

PMID- 27042538
TI  - Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role
      Redefined!!
AB  - Role of progesterone in reproductive medicine is evolving with its suggested
      clinical role for the hormonal and nonhormonal actions in reproductive medicine.
      The main function of progesterone is to induce 'secretory' changes in endometrium
      that is further complimented by its immunomodulatory and anti-inflammatory
      actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better
      implantation. MHRA recommends Serum Progesterone levels >=14ng/ml in the mid
      luteal phase for supporting pregnancy adequately. Oral Natural Micronized
      Progesterone SR formulation represents a therapeutic advance in this direction
      offering 'therapeutic compliance' with oral formulation while avoiding the local
      side effects related to long-term patient compliance in reproductive disorders.
      The formulation offers round the clock efficiency and efficacy with single dose
      administration thereby improving patient convenience and compliance. This
      formulation has been marketed globally since 1986 utilizing the well validated
      drug delivery system involving Methylcellulose base. The clinical utility of this
      formulation is further suggested especially in various conditions related with
      luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase
      support in ART. The level of evidence has been quite robust with several clinical
      studies including Prescription Event Monitoring and Investigator initiated
      studies supporting the clinical role of oral NMP SR formulation especially in
      'Real world' clinic settings for Luteal phase insufficiency that may be
      physiological or iatrogenic. 

PMID- 27042539
TI  - A Prospective Study on Radiological and Functional Outcome of Displaced Tongue
      Type Intra-Articular Calcaneal Fractures Treated by Percutaneous Screw Fixation.
AB  - INTRODUCTION: Calcaneal fractures have posed a challenge to orthopaedic surgeon
      for many years. The major problem is to reconstruct the fracture and improve
      healing of the fracture and also the surrounding tissues. Anatomic restoration of
      the three-dimensional anatomy of the calcaneum is the goal of surgical management
      of calcaneal fractures. Over the years, various techniques have been developed to
      accomplish this goal. AIM: To determine the functional outcome in displaced
      tongue-type calcaneal fracture treated by percutaneous screw fixation. MATERIALS
      AND METHODS: A prospective study was conducted from October 2012 and September
      2014. A total of 23 patients with intra-articular 'tongue type' calcaneal
      fractures were included in the study. Complete clinical and radiological
      evaluation was done. The surgical procedure encompassed closed reduction and
      fixation with two criss-cross 6.5 mm cannulated cancellous across the fracture
      site under fluoroscopic guidance. Postoperatively, on day three ankle and toe
      mobilization was begun. Non-weight bearing crutch mobilization was begun on
      postoperative day three. Reviews were done at 6 weeks, 12 weeks and 24 weeks
      postoperatively. At 6 weeks partial weight bearing mobilization was started. Full
      weight bearing was begun at 12 weeks. The patient was finally reviewed at 24
      weeks and assessment of ankle function was done as per the Maryland foot scoring
      system. Radiographs were compared and preoperative and postoperative Gissane's
      and Bohler's angles were also compared. The results were analysed as per
      descriptive statistics (frequency, percentage). The complications noted were
      documented. RESULTS: Of the 23 patients under the study, three had excellent
      results with mean score of 90, 17 had good results with mean score of 82.94 and
      three had fair results with mean score of 74. Only one patient had subtalar
      arthritis as a complication. No other complications were seen. CONCLUSION:
      Percutaneous screw fixation of tongue type calcaneal fractures is a very
      effective surgical technique.

PMID- 27042540
TI  - A Comparative Study between Closed Reduction and Cast Application Versus
      Percutaneous K- Wire Fixation for Extra-Articular Fracture Distal end of Radius.
AB  - INTRODUCTION: In extra-articular distal radius fractures closed reduction and
      casting has been the mainstay of treatment, difficulty lies in predicting and
      maintaining the proper reduction at final union. Percutaneous K-wire
      stabilization is also a widely accepted treatment option, but there is no
      consensus on its outcome in comparison to closed reduction and casting. AIM: To
      evaluate the results of closed reduction and casting versus closed reduction with
      percutaneous K wire fixation and casting in the treatment of the distal radius
      extra-articular fracture with reference to the restoration of radial height,
      radial inclination, volar tilt of the distal articular surface and to assess the
      functional outcome of the same measured by the Gartland and Werley demerit
      scoring system. MATERIALS AND METHODS: Prospective study was conducted on 60
      patients attending the Department of Orthopaedics, from December 2013 to May 2015
      with extra-articular fractures (AO type 23-A2 and 23-A3) of distal radius and
      fulfilling all the inclusion and exclusion criteria. The cases were randomly
      divided into two equal groups of 30 patients, the first group treated by closed
      reduction and below elbow cast application, while the second group were treated
      by closed reduction percutaneous K-wire application and below elbow cast
      application. The radiological outcome of both groups were evaluated by measuring
      the Volar inclination, Radial inclination and Radial height, while the functional
      outcome was evaluated by the demerit scoring system of Gartland and Werley.
      RESULTS: The Cast application group had 13 excellent, 9 good, 7 fair and 1 poor
      result the mean outcome score of the group was 5.2. The K wiring group had 11
      excellent, 13 good, 5 fair and 1 poor result, the mean score of the group was
      5.17. The unpaired student's t-test on the values obtained from both groups
      yielded a p-value of 0.9816. The mean radial height in the Cast application group
      was 8.033mm while the mean in the k wiring group was 11.783mm. The mean volar
      tilt was 4.867 degrees and 7.5 degrees respectively. The mean radial inclination
      was 14.23 degrees and 19.1respectively. Unpaired student's t-test on the values
      revealed a p-value of 0.0001 for all three. CONCLUSION: We concluded that closed
      reduction with percutaneous K-wire fixation under C-arm for treatment of extra
      articular fractures of distal radius gives statistically significantly better
      radiological outcome than treatment with closed reduction and casting alone, but
      there is no statistically significant difference in functional outcome.

PMID- 27042541
TI  - Early Conversion of External Fixation to Interlocked Nailing in Open Fractures of
      Both Bone Leg Assisted with Vacuum Closure (VAC) - Final Outcome.
AB  - INTRODUCTION: Management of compound grade III fractures of both bone leg
      includes external stabilization for long period, followed by various soft tissue
      coverage procedures. Primary interlocking of tibia had been also done with
      variable results. External fixation for long time without any bone loss often
      leads to infected nonunion, loss of reduction, pin tract infection and failure of
      fixation, primary interlocking in compound grade III fractures had shown high
      medullary infection rate. We managed all cases of compound grade III A/B
      fractures with primary external fixation, simultaneous wound management using
      vacuum assisted closure (VAC) followed by early conversion to interlocking within
      2 weeks of fixator application. AIM: To determine the effectiveness of vacuum
      assisted closure (VAC) for the early conversion of external fixator to definitive
      interlocking in open fractures of the both bone leg. MATERIALS AND METHODS: In
      current study we selected 84 cases of compound grade IIIA/B diaphyseal fractures
      of both bone leg during period of May 2010 to September 2013. We managed these
      cases by immediate debridement and application of external fixation followed by
      repeated debridement, application of vacuum assisted closure (VAC) and conversion
      to interlocking within two weeks. RESULTS: Out of 84 cases union was achieved in
      80(95%) of cases with definitive tibial interlocking. Excellent to good result
      were obtained in 77(91.8%) of cases and fair to poor result seen in rest of
      7(8.2%) of cases according to modified Ketenjian's criteria. 5 out of these 7
      poor result group cases were from Compound Grade III B group to start with. Deep
      infection rate in our series were 7% i.e. total 6 cases and 4 out of these were
      from compound Grade III B group to start with. CONCLUSION: Vacuum assisted
      closure (VAC) give a good help for rapid closure of the wound and help in early
      conversion to definitive intramedullary nailing. Reamed nail could well be used
      in compound grade IIIA/B fractures without increasing the risk of infection. It
      gives better stability to fracture site and lessen the risk of implant failure.

PMID- 27042542
TI  - Accuracy of Needle Placement into the Intra-Articular Space of the Knee in
      Osteoarthritis Patients for Viscosupplementation.
AB  - INTRODUCTION: Knee osteoarthritis is characterized by inflammation in the intra
      articular space or synovial membrane, breakdown of articular cartilage, and
      sclerosis of the subchondral bone. Intra-articular injections of Sodium
      hyaluronate which have viscoelastic and protective effect on articular cartilage
      and restores normal articular homeostasis. The efficacy of these injections is
      diminished when they are placed inadvertently outside the joint. For the maximum
      benefit, injection of hyaluronic acid derivatives needs to be placed accurately
      into the knee joint. AIM: The study was performed to know the correct placement
      of needle inside the knee joint prior to Viscosupplementation by fluoroscopy
      using a contrast material. MATERIALS AND METHODS: The accurate placement of
      needle was evaluated in a prospective series of 94 consecutive injections in
      patients without clinical knee effusion. All the injections were performed by
      single orthopaedic surgeon using a 5 cm 21-gauge needle through anterolateral,
      and lateral midpatellar portals. The needle placement in the knee joint was
      confirmed with fluoroscopy using the contrast material. RESULTS: The accuracy
      rates through Lateral midpatellar and Anterolateral portals were lower than
      expected rate (100%). A total of 43 out of 47 injections were intra-articular,
      indicating accuracy of 91.5% through lateral midpatellar portal, 41 out of 47
      injections were intra-articular through anterolateral portal with accuracy of
      87.4%. CONCLUSION: Study showed that the accuracy of needle placement was higher
      through Lateral midpatellar than the Anterolateral portal.

PMID- 27042543
TI  - Correlation between MRI and Arthroscopy in Diagnosis of Shoulder Pathology.
AB  - INTRODUCTION: Shoulder pain can cause significant pain, discomfort and reduce the
      ability to perform activities of daily living, thus making it the third most
      common cause of musculoskeletal consultation. The current gold standard
      diagnostic investigation is arthroscopy. MRI is a proved sensitive and accurate
      non-invasive tool in investigating shoulder pathology, but false and misleading
      results are equally reported. AIM: The aim of the study is to compare the
      efficacy of MRI in diagnosing shoulder pathologies in comparison to arthroscopy,
      considering arthroscopy as the gold standard. MATERIALS AND METHODS: Thirty nine
      consecutive patients, between 18-80 years of age, presenting with chronic
      shoulder pain or instability of more than 6 weeks, or with clinical signs of
      impingement or tear were included in the study. MRI of the shoulder joint was
      done followed by shoulder arthroscopy. The data collected was analysed for the
      significant correlation between MRI of shoulder and arthroscopic findings by
      kappa statistics. RESULTS: Out of 39 patients, Rotator cuff (RC) tear was the
      most common pathology. MRI showed excellent sensitivity in the diagnosis of
      rotator cuff tears (0.91) and osteochondral defects (OCD), very good sensitivity
      for Bankart's lesion (0.8) and had poor sensitivity to detect SLAP tear (0.15).
      MRI was specific for all shoulder pathologies. MRI detected RC tears with kappa
      score of 0.73, Bankart's tear and OCD's with kappa score of 0.83 and 1.0
      respectively and SLAP lesion with kappa score of 0.14. The accuracy of MRI was
      highest in diagnosing OCD's (1.0), followed by RC tear (0.9), Bankart's tear
      (0.9) and accuracy was least in diagnosing SLAP lesion (0.7). False negative
      results were more than false positives. CONCLUSION: The present study supports
      that MRI is effective in diagnosing rotator cuff tears, Bankart's tear and
      ostechondral defects but was not found to be helpful in diagnosing SLAP lesions.
      MRI and arthroscopy have complimentary roles in the diagnosis of shoulder
      pathology.

PMID- 27042544
TI  - Prevalence of Thyroid Disorders in Children at a Tertiary Care Hospital in
      Western India.
AB  - INTRODUCTION: Thyroid hormone abnormalities are the commonest endocrine disorder
      in India and also the commonest preventable cause of mental retardation. In the
      absence of neonatal screening, thyroid disorders remain largely unrecognized in
      Indian children. AIM: To determine the prevalence, clinical profile, aetiology
      and associated co-morbidities of thyroid dysfunction in children. MATERIALS AND
      METHODS: A prospective, hospital based, observational study was conducted at a
      tertiary care hospital in Western India. Children below 12 years of age visiting
      the Pediatric out-patient department (OPD) and in-patient department (IPD) were
      included if they had clinical suspicion of thyroid dysfunction. Demographic data
      and clinical features of the recruited children were noted along with family
      history of thyroid disorders and use of iodized salt. Thyroid profile consisting
      of Tri-iodothyronin (T3), Thyroxin (T4) and Thyroid stimulating hormone (TSH)
      levels were tested in all. Investigations were also carried out to look for the
      cause and complications of hypothyroidism. These children were also followed up
      with appropriate therapy to look for response of therapy and complications to the
      same. RESULTS: Sixty five children were found to have thyroid function
      abnormalities, 61 having hypothyroidism and 4 having hyperthyroidism. There was a
      low prevalence of goiter. The clinical feature of patients with hypo and
      hyperthyroidism was similar to other reported studies. The commonest aetiology of
      hypothyroidism was found to be dyshormonogenesis. A host of co-morbidities was
      observed along with thyroid dysfunction. On follow up with appropriate therapy,
      most of the children became euthyroid and complications were observed in only a
      minority. CONCLUSION: There is a high prevalence of thyroid dysfunction in
      children in western India and need for similar studies from different regions of
      the country covering larger population are well appreciated.

PMID- 27042545
TI  - Public-Private Partnership in Health Care: A Comparative Cross-sectional Study of
      Perceived Quality of Care Among Parents of Children Admitted in Two Government
      District-hospitals, Southern India.
AB  - INTRODUCTION: Perceived better quality of care draws lower socio-economic classes
      of Indians to more expensive private setups, leading to poverty illness poverty
      cycle. Urgent measures need to be taken to improve perceived quality of public
      hospitals. The present study compares the difference in perceived quality of care
      among parents of children admitted at two government district hospitals.
      MATERIALS AND METHODS: A cross-sectional, comparative, questionnaire based study
      was conducted between February 2011 and February 2012 at Government medical
      college hospitals of two district headquarters in South-India: one with private
      public-partnership (PPP-model); another directly operated by government - Public
      Hospital-model (PH-model). A total of 461 inpatients from the PH model hospital
      and 580 from the PPP model hospital were eligible. Patients who left against
      advice (LAMA) (n=44 in PH and 19 in PPP) and expired (n=25 in PH and 59 in PPP)
      were excluded. Fourteen incomplete forms from PH and 10 from PPP model hospital
      were also excluded. Responders rated perception on a 1-5 scale in each domain:
      accessibility of health-facility, time spent waiting, manner and quality of
      physician, manner and quality of nurse, manner and quality of supporting staff,
      perception of equipment, explanation of treatment details and general comfort.
      The responders also rated overall satisfaction on a 1-10 scale. In the 1-5 scale,
      rating>=4 in each domain was considered good. Rating>=8 in 1-10 scale was
      considered satisfaction. RESULTS: Responders from PPP-model hospital were
      significantly more satisfied than those from PH-model {n=529 (91.2%) vs. n=148
      (32.1%) p<0.001}. This was true even when controlled for age-group, sex, maternal
      education, family-type, days of hospital-stay and socioeconomic class {O.R.(CI)
      =23.58 (16.13-34.48); p<0.001} by binary logistic regression model. In the PPP
      model hospital the time spent waiting for treatment {4.28(2.07-8.82), p<.001} and
      manner of support staff {3.64(1.02-12.99), p=0.04} significantly predicted
      satisfaction. In PH-model hospital explanation given regarding treatment details
      significantly predicted overall satisfaction {2.99(1.61-5.54), p<.001}.
      CONCLUSION: Perceived quality of hospital care, as evidenced by the satisfaction
      and perception ratings of responders, was better in PPP-model hospital. This
      model could be emulated in developing countries to draw patients of lower socio
      economic classes to tertiary-care public hospitals which are less expensive.

PMID- 27042546
TI  - Neonatal Intestinal Obstruction: A 15 Year Experience in a Tertiary Care
      Hospital.
AB  - INTRODUCTION: Neonatal intestinal obstruction is the most common surgical
      emergency in a newborn requiring prompt intervention. There are only very few
      studies done in world regarding pattern of neonatal intestinal obstruction. AIM:
      This study was conducted to see the aetiological spectrum of neonatal intestinal
      obstruction and to find out the problems and outcome of surgical management.
      MATERIALS AND METHODS: This study was done retrospectively to include all
      operated cases of neonatal intestinal obstruction from June 2000 to May 2015 and
      various factors affecting outcome were analysed. RESULTS: A total of 298 newborns
      were included in the study. Male-female ratio was 1.8:1. Gestational age was
      variable from 32 to 42 weeks (mean = 37.5 weeks) and birth weight from 1.4 to
      3.5kg (mean= 2.25 kg). Mean age of presentation was 6 days with intestinal
      atresia (49.6%) as the commonest cause. Other causes were Hirschsprung (13%),
      Malrotation gut (11.7%), Meconium ileus (7.3%), patent VID (5%), duodenal
      obstruction (4%), duplication cyst (3.7%), obstructed hernia (2.7%) and others
      (2.7%). Mortality rate was 16.4% with sepsis both pre as well as post operative
      as the main cause of mortality. CONCLUSION: The morbidity and mortality of
      neonatal intestinal obstruction has improved over last few years mainly due to
      antenatal detection, early intervention, meticulous resuscitation before surgery
      along with good NICU care.

PMID- 27042547
TI  - Changes in Habitual and Active Sagittal Posture in Children and Adolescents with
      and without Visual Input - Implications for Diagnostic Analysis of Posture.
AB  - INTRODUCTION: Poor posture in children and adolescents has a prevalence of 22-65%
      and is suggested to be responsible for back pain. To assess posture, photometric
      imaging of sagittal posture is widely used, but usually only habitual posture
      positions (resting position with minimal muscle activity) are analysed. AIM: The
      objective of this study was 1) to investigate possible changes in posture
      describing parameters in the sagittal plane, when the subjects changed from a
      habitual passive posture to an actively corrected posture, and 2) to investigate
      the changes in posture parameters when an actively corrected posture was to be
      maintained with closed eyes. MATERIALS AND METHODS: In a group of 216 male
      children and adolescents (average 12.4 +/- 2.5 years, range 7.0 - 17.6 years),
      six sagittal posture parameters (body tilt BT, trunk incline TI, posture index
      PI, horizontal distances between ear, shoulder and hip and the perpendicular to
      the ankle joint) were determined by means of photometric imaging in an habitual
      passive posture position, in an actively erect posture with eyes open, and in
      active stance with eyes closed. The change in these parameters during the
      transition between the posture positions was analysed statistically (dependent t
      Test or Wilcoxon-Test) after Bonferroni correction (p<0.004). RESULTS: When
      moving from a habitual passive to an active posture BT, TI, PI, dEar, dShoulder,
      and dHip decreased significantly(p< 0.004). When the eyes were closed, only the
      perpendicular distances (dEar, dShoulder, and dHip) increased significantly. The
      parameters that describe the alignment of the trunk sections in relation to each
      other (BT, TI, PI), remained unchanged in both actively regulated posture
      positions. CONCLUSION: Changes in sagittal posture parameters that occur when a
      habitual passive posture switches into an active posture or when an active
      posture is to be maintained while the eyes are closed can be used for diagnostic
      purposes regarding poor posture and posture regulation.

PMID- 27042548
TI  - A Hospital Based Study to Establish the Correlation between Recurrent Wheeze and
      Vitamin D Deficiency Among Children of Age Group Less than 3 Years in Indian
      Scenario.
AB  - INTRODUCTION: Early childhood wheezing is a heterogeneous condition, which has
      several phenotypic expressions and a complex relationship with the development of
      asthma later in life. New studies indicate the prevalence of recurrent wheeze to
      be associated with Vitamin D deficiency. This has not been explored in Indian
      settings widely, mandating this exploration. AIM: To determine the severity of
      Vitamin D deficiency and its association with recurrent wheeze in children less
      than 3 years of age. MATERIALS AND METHODS: Consecutive type of non-probability
      sampling was followed for selection of study subjects with a total sample size to
      be 122 children in the Hospital setting. A pre- formed, pre- tested, structured
      interview schedule was used to obtain information. Estimation of 25 (OH) Vitamin
      D was done using ELISA method. Kit used for estimation was DLD Diagnostika GMBH
      25(OH) Vitamin D ELISA from Germany. Standard statistical tools were used
      including Logistic regression analysis, and ROC curve, p value <0.05 was
      considered to be statistically significant. SPSS software version 17.0 was used.
      RESULTS: Each 10ng/ml decrease in Vitamin D level is associated with 7.25%
      greater odds of wheezing. Our study also suggests, exclusive breast feeding and
      delaying of complementary feeding beyond 6 months of age are significant
      predictors of Vitamin D deficiency and have indirect association with increased
      incidence of wheezing in children. CONCLUSION: The study concluded that Vitamin D
      deficiency is associated with increased risk of recurrent wheezing.

PMID- 27042549
TI  - The Effects of Fetal Movement Counting on Pregnancy Outcomes.
AB  - INTRODUCTION: Counting fetal movements may lead to timely assess fetal health and
      prevent the adverse effects of pregnancy. AIM: The aim of this study was to
      determine the effect of fetal movement counting on pregnancy outcomes. MATERIALS
      AND METHODS: In a randomized controlled trial, 208 women with singleton pregnancy
      were randomly divided into two groups of fetal movement counting and control.
      Pregnancy outcomes were compared between the two groups. Data were analysed with
      SPSS and p<0.05 was considered significant. RESULTS: There was no significant
      difference in the mean maternal concern (p=0.36), admission to hospital due to
      the decreased fetal movements (p=0.99), birth weight (p=0.21), Apgar score
      (p=0.51), the mean of gestational age at the time of decreased fetal movements
      (p=0.49) and mode of delivery (p=0.69) between the two groups. There were no
      cases of premature labour, intrauterine growth retardation and fetal death in the
      two groups. CONCLUSION: Pregnancy outcome was similar in the two groups of fetal
      movement counting and control. Further studies are needed to evaluate the effect
      of fetal movement counting on the major outcomes of pregnancy such as
      intrauterine fetal death.

PMID- 27042550
TI  - A Neonatal Septic Arthritis Case Caused by Klebsiella pneumoniae: A Case Report.
AB  - Septic arthritis is encountered very rarely during the neonatal period and its
      diagnosis can delay because of atypical symptoms, thus it may lead to serious
      sequelae. The sequale can be prevented by early diagnosis and concomitant
      treatment. In neonates, pain can be experienced as a result of pseudoparalysis
      and of movement of the effected joints. A 17-day-old neonatal patient was brought
      to our hospital with complaint of unrest and then diagnosed with septic arthritis
      due to propagation of Klebsiella pneumoniae in joint fluid culture was
      represented because of the rarity of such a case. 

PMID- 27042551
TI  - A Case Report of Cornelia De Lange Syndrome in Northern Iran; A Clinical and
      Diagnostic Study.
AB  - As a rare multisystem congenital anomaly disorder, Cornelia de Lange syndrome
      (CdLS) is featured by delayed growth and development, distinct facial dimorphism,
      limb malformations and multiple organ defects. CdLS is a genetic syndrome
      affecting 1/10000-1/60000 neonates with unknown genetic basis. Delayed growth and
      development, hirsute, structural anomalies of the limbs and distinct facial
      dimorphism are considered as its main clinical characteristics. Introducing CdLS
      cases of different ethnic backgrounds could add distinctions to the phenotypic
      picture of the syndrome and be useful in diagnosis. Early diagnosis and decreased
      death rates are achievable through enhanced awareness on this syndrome. We
      present here a 45-day-old girl, as the first case of Cornelia in Golestan
      (Northern Iran), referred to our hospital with the symptoms as mentioned above. 

PMID- 27042552
TI  - Gerbode Defect of Congenital Variety in an Infant: A Case Report.
AB  - Gerbode defect is a rare communication from left ventricle to right atrium. It is
      of two types: congenital versus acquired OR Direct (type I) versus Indirect (type
      II). Acquired forms are more common and increasingly reported than congenital. We
      report a second Indian case of such a rare defect and highlight the salient
      points of all such previously reported cases to make aware the clinicians and
      paediatricians of need of early diagnosis and timely surgery/ referral for
      successful outcome. 

PMID- 27042553
TI  - Hepatic Venous Waveform, Splenoportal and Damping Index in Liver Cirrhosis:
      Correlation with Child Pugh's Score and Oesophageal Varices.
AB  - INTRODUCTION: Clinical assessment of chronic liver disease is done by Modified
      Child Pugh's and Model for end-stage liver disease scoring system. Measurement of
      hepatic venous pressure gradient (HVPG) and Upper GI Endoscopy are considered the
      gold standards for measurement of portal hypertension in cirrhotics. There is a
      need for non-invasive evaluation of portal hypertension. Ultrasonography with
      colour and spectral Doppler evaluation may be an effective, rapid and inexpensive
      alternative. AIM: To evaluate hepatic venous waveform, damping index,
      splenoportal index in patients of cirrhosis on Colour Doppler ultrasound, also
      predict severity of portal hypertension and presence of oesophageal varices.
      MATERIALS AND METHODS: Thirty patients of chronic liver disease were included in
      the study. Ultrasound and colour Doppler was done to look hepatic venous waveform
      pattern, Damping Index (DI), and Splenoportal Index (SPI). Contrast-enhanced
      Computed Tomography scan (CT) was done if renal function tests were normal, else
      endoscopy when the renal function tests were deranged to look for oesophageal
      varices. RESULTS: Twenty two (73.3%) patients had monophasic waveform. Biphasic
      and triphasic waveforms were seen in 4 (13.3%) cases. Twenty two patients (73.3%)
      had monophasic waveforms and majority of them were in class C. This distribution
      of hepatic vein waveform was statistically significantly with the Child Pugh's
      class (p<0.05). Twenty patients (66.7%) had value of Damping index more than >0.6
      where majority of patients (18) belonged to class C and 2 in class B. There was a
      positive correlation between Child Pugh's total score and Damping index (r=0.614;
      p<0.05). There was weak positive correlation between splenoportal index and Child
      Pugh's score (r=0.269; p=0.15). CONCLUSION: Change in triphasic to monophasic
      waveform and DI >0.6 suggests severe liver dysfunction and is associated with
      severe portal hypertension. Hepatic venous waveform pressure changes, DI and SPI
      have no value in predicting presence of oesophageal varices.

PMID- 27042554
TI  - Evaluation of Lacrimal Gland Dimensions and Volume in Turkish Population with
      Computed Tomography.
AB  - INTRODUCTION: Computed tomography (CT) is a widespread method for evaluating head
      and neck pathologies. The lacrimal glands (LGs) are usually visible in routine
      head and neck CT scans. LG pathologies usually manifests with changes in gland
      sizes, so it is important to know the normal values of the LG dimensions and
      volume. The LG sizes may change with age, gender and race. The normal values of
      LG dimensions and volume in Turkish population was not reported before. AIM: The
      aim of this study was to evaluate the dimensions and volumes of the LGs by CT in
      a Turkish population. MATERIALS AND METHODS: Two hundred seventeen consecutive
      paranasal CT scans of subjects evaluated retrospectively. Measurements of LG
      dimensions were performed in axial and coronal paranasal CT images. The LG volume
      was calculated with Aquarius software by outlining the gland in all consecutive
      axial images. RESULTS: Four hundred orbits of 200 subjects were included to the
      study. The mean axial LG length in right and left orbits were 16.2+/-2.0 mm and
      16.0+/-2.0 mm and the mean axial width of the right and left orbits were 4.1+/
      0.7 mm and 4.0+/-0.7 mm. The right and left LG mean values for coronal length and
      width were equal 18.3 +/-2.2 mm and 4.1+/-0.7mm respectively. The mean LG volume
      was 0.617+/-0.210 cm(3) in right and 0.597+/-0.197 cm(3) in the left orbits.
      There were statistically significant differences in the axial width and volume of
      the LG according to sides, however there was no significant difference according
      to gender. Age and LG measurements were negatively correlated. CONCLUSION: Our
      study may serve as a guide to determine the average values of the LG measurements
      in Turkish population and find out the orbital pathologies that involves the LG.

PMID- 27042555
TI  - A Comparative Study of Sonographic Grading of Renal Parenchymal Changes and
      Estimated Glomerular Filtration Rate (eGFR) using Modified Diet in Renal Disease
      Formula.
AB  - INTRODUCTION: The sonographic findings are of help in evaluating the
      nephrological diseases. Glomerular filtration rate is another parameter for
      assessing the reserved renal function and an indicator of prognosis. In clinical
      practice GFR estimation (eGFR) is done by using a mathematical formula. In our
      study, we compared the sonographic grading of renal parenchymal changes with eGFR
      calculated using Modified Diet in Renal Diseases formula based on serum
      creatinine, age, gender and ethnicity. AIM: To evaluate the relevance of
      sonographic grading of renal parenchymal changes in assessing the severity of the
      renal disease and comparing it to the eGFR calculated using MDRD formula based on
      the age, gender and serum creatinine value of the patient. MATERIALS AND METHODS:
      The adult patients with suspected kidney disease referred for sonography of
      abdomen were our study participants. As per our study design following strict
      inclusion and exclusion criteria, patients were selected as study participants
      and for each of the patient's renal parenchymal status, serum creatinine, age,
      gender and ethnicity were documented. RESULTS: A total of 70 patients were our
      study participants, out of which 67.1% were males and 32.9% were females. Our
      study showed a linear correlation between sonographic grading of renal
      parenchymal changes with eGFR. CONCLUSION: We conclude that by evaluating the
      kidneys with sonography and calculating eGFR using MDRD formula the renal status
      will be more accurately interpreted.

PMID- 27042556
TI  - Segmental Comparison of Peripheral Arteries by Doppler Ultrasound and CT
      Angiography.
AB  - INTRODUCTION: Diseases of peripheral arterial system are one of the common causes
      of limb pain, especially in elderly patients. Here we analyse non invasive
      imaging of peripheral arterial segments. AIM: Aim of the study was to compare
      arterial diseases of extremities using Doppler ultrasound and CT angiography, and
      to find the better non-invasive modality of choice. MATERIALS AND METHODS: Fifty
      patients {14 patients with upper limb complaints (15 upper limbs) and 36 patients
      with lower limb complaints (72 lower limbs)} of peripheral arterial disease
      underwent Doppler ultrasound (USG) and CT Angiogram (CTA). Arterial systems
      divided into anatomic segments and luminal narrowing were compared using gray
      scale Doppler ultrasound and axial images of arterial phase of CT angiogram.
      Using statistical methods, sensitivity, specificity and accuracy of Doppler
      ultrasound and CT angiography were determined. RESULTS: Six hundred and nineteen
      arterial segments were studied with CT angiography and Doppler ultrasound. Of
      which 226 diseased segments were identified in CT angiography. Doppler
      overestimated narrowing by one grade in 47 segments, by two grade in 11 segments,
      by three grades in 30 segments and by four grades in 22 segments; underestimated
      by one grade in 28 segments, by two grades in 9 segments, by three grades in 5
      segments and by four grades in 3 segments. Significant statistical difference
      exists between Doppler USG and CT angiography. Doppler showed good correlation
      with CT angiography in 74%, but, Doppler overestimated stenosis grade in a
      significant percentage. The sensitivity, specificity and accuracy of Doppler USG
      compared with CT angiography was 93.36%, 82.44%, and 86.42%. CONCLUSION: Duplex
      Doppler can be the first investigation in excluding peripheral arterial disease,
      especially for evaluation of infra inguinal region of lower limbs and from second
      part of the subclavian artery in upper limbs.

PMID- 27042557
TI  - Evaluation of CT and MRI Findings among Patients Presented with Chief Complaint
      of Headache in Central India.
AB  - INTRODUCTION: Headache is one of the most common presenting complaints in day to
      day medical practice however the secondary causes of headache are uncommon. Thus,
      appropriate selection of headache patient (Pt) is important to determine those
      that require neuroimaging due to likely secondary cause. Red flags and Clinical
      warning criterion (CWC) act as a screening tool to help in identifying those who
      may get benefit from neuroimaging. AIM: To evaluate the findings of computed
      tomography (CT) and Magnetic Resonance Imaging (MRI) among patients presented
      with the chief complaint of headache and to compare the findings between two
      groups of patients. MATERIALS AND METHODS: This retrospective observational study
      was carried out in 500 selected patients, who underwent CT or MRI scan of head in
      Peoples College of Medical Sciences and Research centre, Bhopal, MP during the
      period of 2 year in between Jan 2013 to Dec 2014. Siemens Somatom sensation 40
      slice MDCT and Siemens magnetom 1.5T MRI scanner were used for imaging. Five
      hundred patients of 10 to 70 year age were selected for the study based on our
      criterions of selection. RESULTS: All 500 patients were divided in to two groups
      A and B based on presence or absence of red flag signs and CWC signs. Group A
      consists of 48 patients having one or more red flag or CWC signs and group B
      consists of 452 patients those don't have any above signs. 29 cases (60.4%) out
      of total 48 cases of group A is suffering from chronic headache as compared to 97
      cases (21.5%) out of total 452 patients of group B is having positive findings (p
      value<0.05). Out of 500 patients, only 29 cases (5.8%) revealed some form of
      brain parenchymal pathology whereas other associated findings were seen in 97
      cases e.g. sinusitis in 58 (11.6%), bone related pathology in 26 (5.2%) and
      chronic suppurative otitis media (CSOM) in 13 (2.6%) patients. CONCLUSION: CT/MRI
      in patients without red flag or CWC sign yields very low percentage of clinically
      significant positive findings in neuroimaging. In the absence of these, the only
      reason for CT or MRI scan seems to reassure the patients and their loved ones. CT
      or MRI as a screening tool in these patients has limited value in term of cost
      effectiveness.

PMID- 27042558
TI  - Accuracy of Common Femoral Artery Doppler Waveform Analysis in Predicting
      Haemodynamically Significant Aortoiliac Lesions.
AB  - INTRODUCTION: Doppler ultrasound is cost-effective and accurate noninvasive
      method for evaluation of peripheral arterial disease. However, there is
      difficulty in detection of aortoiliac lesions due to inadequate visualization of
      aortoiliac arteries in many patients. The Doppler waveform changes occurring
      distal to significant stenosis or occlusion are well documented. Accordingly,
      common femoral artery (CFA) Doppler waveform analysis may be used to predict
      haemodynamically significant proximal aortoiliac lesions. AIM: To evaluate the
      accuracy of Doppler waveform analysis at the CFA for diagnosing haemodynamically
      significant aortoiliac stenosis or occlusion in patients of peripheral arterial
      disease. MATERIALS AND METHODS: A total of 67 patients (114 aortoiliac segments)
      with suspected peripheral arterial disease were retrospectively evaluated and
      labeled as normal or abnormal by analysing the Doppler waveform of CFA. The
      triphasic waveform with normal reversal pattern was categorized as normal, while
      low velocity biphasic or monophasic waveform were labeled as abnormal and
      indirect diagnosis of normal or diseased (>50% stenosis or occlusion) aortoiliac
      segment was made. The results were compared to intra-arterial angiography,
      considered as the gold standard. RESULTS: The Doppler waveform analysis of CFA
      was abnormal in 41 out of 114 common femoral arteries, while intra-arterial
      angiography showed significant stenosis (21 arteries) or occlusion (26 arteries)
      in 47 (41%) of 114 aortoiliac segments in 67 patients. Out of 67 normal
      aortoiliac segments seen on angiography, the CFA waveform analysis was
      interpreted as normal in 62 segments. An abnormal CFA waveform could diagnose
      significant aortoiliac lesion with 87% sensitivity, 92% specificity, 89% Positive
      Predictive Value (PPV), 91% Negative Predictive Value (NPV) and 90% accuracy
      using angiography as the gold standard. The low velocity monophasic waveform
      which was seen in 38 (33%) of 114 segments was reliable predictor of significant
      aortoiliac disease with 93% positive predictive value. CONCLUSION: CFA Doppler
      waveform pattern analysis is a sensitive and accurate technique for the
      prediction of haemodynamically significant aortoiliac stenosis or occlusion.

PMID- 27042559
TI  - A Co-Presentation of Biliary Ascariasis and Hepatic Hydatidosis.

PMID- 27042560
TI  - A Rare Association of Bilateral and Unilateral Masseter Hypertrophy with
      Hypertrophy of Pterygoids.

PMID- 27042561
TI  - Serial Peak Expiratory Flow Rates in Patients Undergoing Upper Abdominal
      Surgeries Under General Anaesthesia and Thoracic Epidural Analgesia.
AB  - INTRODUCTION: Anaesthesia and upper abdominal surgeries alter lung compliance and
      functional residual capacity resulting from atelectasis. Upper abdominal
      surgeries also cause a decrease in peak expiratory flow rates, cough reflex due
      to pain limited inspiration. AIM: This study aimed to study the effect of
      thoracic epidural analgesia (TEA) on the peak expiratory flow rates in patients
      undergoing upper abdominal surgeries. MATERIALS AND METHODS: A total of 44
      patients posted for elective surgery were enrolled. Group 1 patients received GA
      + 0.125% bupivacaine infusion TEA and Group 2 received GA + Inj. Diclofenac
      sodium 50 mg slow i.v. TID for Postoperative analgesia. Haemodynamics, VAS pain
      score, PEFR measurements were done at 60 minutes, 24 hours, 48 hours and 4 days
      after surgery in both groups. ABG analysis was taken pre operatively and 24 hours
      after surgery. RESULTS: The SBP and DBP values obtained at 60 minutes (p<0.016)
      24 and 48 hours (p<0.001) and day 4 (p<0.02) postoperative showed highly
      significant difference between the two groups which indicate better haemodynamic
      parameters in patients receiving epidural analgesia. Postoperatively the
      difference in PEFR values at 60 minutes, 24 hour, 48 hour and day 4 were very
      highly significant. (p<0.001). Group1 had a 10.739% deficit on day 4 from its pre
      operative baseline value while group 2 showed a 34.825 % deficit which was very
      highly significant (p<0.001). The difference in VAS scores recorded at 60
      minutes, 24 hours, 48 hours and day 4 post op were very highly statistically
      significant (p < 0.001). The ABG taken at 24 hours shows statistically
      significant difference with patients in group 2 showing decreased values in pCO2
      and pO2 reflecting poorer ventilation and oxygenation. CONCLUSION: Thoracic
      epidural analgesia provides superior analgesia, better cough reflex as seen by
      better PEFR values, were haemodynamically more stable and their ABG values were
      better than the NSAID group.

PMID- 27042562
TI  - Spinal Anaesthesia is Safe in a Patient with Wolff-Parkinson-White Syndrome
      Undergoing Evacuation of Molar Pregnancy.
AB  - Wolff-Parkinson-White (WPW) syndrome is an uncommon cardiac condition where there
      is an abnormal band of atrial tissue connecting atria and ventricles which can
      electrically bypass atrioventricular node. The anaesthetic management in these
      patients is challenging as life threatening complications can occur
      perioperatively like paroxysmal supraventricular tachycardia and atrial
      fibrillation. Also, regional anaesthetic technique like subarachnoid block is a
      safe and cost effective alternative to general anaesthesia as it avoids
      polypharmacy. We report the successful anaesthetic management of Wolff Parkinson
      White syndrome in a primi with hydatiform mole posted for suction and evacuation.

PMID- 27042563
TI  - Use of ECT in Nepal: A One Year Study From the Country's Largest Psychiatric
      Facility.
AB  - INTRODUCTION: Electro-Convulsive Therapy (ECT) refers to the electrical
      stimulation of the brain to produce seizures for therapeutic purpose. Since the
      development of ECT, it's use has been consistent. Inspite of the common use, data
      pertaining to the use of ECT in Nepal is lacking. AIM: This study was undertaken
      with the aim of exploring the clinico-demographic profile of patients treated
      with ECT in the largest psychiatry facility in the country. MATERIALS AND
      METHODS: It is a retrospective descriptive study of patients who were treated
      with ECT after admission in the inpatient psychiatry unit of Universal College of
      Medical Sciences Teaching Hospital, Bhairahawa, Nepal during a period of one year
      (August 2012 to July 2013). RESULTS: Out of 1095 patients admitted during the
      specified period, 81 (7.39%) patients received ECT. About 44.44% of the patients
      belonged to 20-29 years age group. Female patients constituted more than half of
      the subjects (55.56%). Review of diagnostic profile showed that majority of
      patients receiving ECT were suffering from Schizophrenia (44.4%), followed by
      Bipolar Affective Disorder/Mania (29.6%), Depressive disorder (11.1%), Acute and
      Transient Psychotic Disorder (6.2%), Post-partum Psychosis (3.7%) and substance
      induced mood/psychotic disorders (3.7%). A significant majority of subjects
      (75.3%) received about 5-7 ECT treatments. The mean seizure duration after ECT
      treatment was 31.13+/-5.79 seconds. No any major complications were noted during
      ECT treatment. CONCLUSION: This study suggests that ECT, use, as a treatment
      modality is common in young adults and females with Schizophrenia being the most
      common indication. Direct ECT is safe when used judiciously.

PMID- 27042564
TI  - Bullying and Victimization Trends in Undergraduate Medical Students - A Self
      Reported Cross-Sectional Observational Survey.
AB  - INTRODUCTION: Bullying is a form of behaviour that can negatively impact a
      person. It can lead to several deleterious consequences like low self-confidence,
      drop in academic performance and depression. Studies have shown that bullying
      behaviour exists amongst medical students also. In the medical field, it is known
      to negatively impact dispensing of health care and attitudes of medical students
      towards becoming doctors. It is very difficult for medical students to cope with
      such a menace as they are already burdened with a vast curriculum and rigorous
      schedules. There exists paucity of studies regarding bullying amongst
      undergraduate medical students in Indian context. AIM: To study prevalence of
      peer-based bullying and victimization along with their associated factors in
      undergraduate medical students. MATERIALS AND METHODS: Four hundred randomly
      chosen undergraduate medical students were included in the study. Socio
      demographic and personal details including history of substance use were recorded
      in a self-designed case record form. Illinois Bullying Scale was used to assess
      bullying behaviours. Out of total 400 students, 383 completed the survey and this
      data was analysed. RESULTS: In this study, 98.69% participants self-reported to
      having indulged in bullying while 88.77% reported feeling victimized. Physical
      (p<0.001) as well as verbal (p=0.001) bullying was found to be of significantly
      greater severity in males as compared to females. Students of the third year of
      medical school indulged in significantly (p=0.034) greater severity of physical
      bullying than those of other years. Alcohol consumption (p=0.001) and cigarette
      smoking (p<0.001) were significantly associated with physical bullying.
      CONCLUSION: Peer-based bullying and victimization was found to be highly
      prevalent amongst undergraduate medical students. There is an urgent need for
      more detailed studies on bullying in medical students so that remedial measures
      can be initiated and steps to limit such behaviours can be looked at seriously.

PMID- 27042565
TI  - Prevalence of Metabolic Syndrome in Psoriasis Patients and its Relation to
      Disease Duration: A Hospital Based Case-Control Study.
AB  - INTRODUCTION: Previous studies indicate a higher prevalence of metabolic syndrome
      in psoriatic patients. This study aimed to investigate the association of
      metabolic syndrome and its components with psoriasis. It also studied the
      relation between presence of metabolic syndrome and disease duration in psoriasis
      patients. MATERIALS AND METHODS: This was a hospital-based, case-control study
      conducted with 30 clinically diagnosed patients of chronic plaque psoriasis and
      30 age- and sex-matched control subjects. Height, weight, BMI, blood pressure and
      waist circumference were assessed in all the subjects. Fasting levels of serum
      glucose, serum triglycerides and serum HDL were estimated by automated clinical
      chemistry analyser. Metabolic syndrome was diagnosed by the presence of at least
      3 criteria of NCEP ATP III with Asian modification for waist circumference.
      RESULTS: Metabolic syndrome was more common in psoriatic patients than in
      controls but the difference was statistically insignificant (60% vs. 40%, p
      value=0.12). The psoriasis group had a higher prevalence of elevated blood
      glucose levels and higher waist circumference compared to controls. Psoriasis
      patients had a higher prevalence of high triglyceride levels than controls, the
      difference being statistically insignificant (40% vs. 30%, p-value = 0.41). The
      prevalence of low HDL levels was significantly higher in cases compared to
      controls (86.7% vs. 60%, p-value = 0.02). There was no relation between presence
      of metabolic syndrome and duration of psoriasis. CONCLUSION: Our findings suggest
      that metabolic syndrome as well as dyslipidaemia is commoner in psoriasis
      patients. This underlines the need for screening of all psoriasis patients for
      early diagnosis and treatment of associated metabolic syndrome to reduce the high
      burden of morbidity and mortality.

PMID- 27042566
TI  - Stewart Treves Syndrome in a Woman with Mastectomy.
AB  - Stewart Treves Syndrome is an angiosarcoma generally seen long time after radical
      mastectomy in breast carcinoma patients in chronic lymphoedema area. It's an
      angiosarcoma developed on a long standing lymphoedema, following a radical
      mastectomy. An 86-year-old woman was referred to our Dermatology outpatient
      clinic which developed a giant erythematous, oedematous, purplish lobulated
      plaque on her right forearm anteromedially with a few satellite erythematous
      papulonodules on her arm. The pathology revealed spindle-shaped tumour cells
      invading dermis with vascular differentiation into the subcutaneus tissue which
      are compatible with a diagnosis of angiosarcoma. 

PMID- 27042567
TI  - Major Protein of Carcinoembryonic Antigen Gene Family - CD66c, A Novel Marker in
      Colon Carcinoma.
AB  - INTRODUCTION: In view of rising trend of the incidence of colorectal carcinoma in
      the Indian population due to adoption of western lifestyles and behaviours, we
      investigated the expression of the new emerging stem cell biomarker, CD66c in
      colorectal carcinoma of Indian origin. AIM: To study the expression of CD66c in
      human colorectal carcinoma and to correlate level of marker expression with
      tumour staging. MATERIALS AND METHODS: This hospital based prospective study was
      conducted on 26 colorectal carcinoma patients in the age group of 20 years to 70
      years. Surgically resected tumour specimens along with adjacent normal tissue
      were collected taking necessary precautions, paraffin embedded sections were
      prepared and used for histological and immunohistochemical analysis of CD66c.
      STATISTICAL ANALYSIS: Descriptive statistical measures like mean, standard
      deviation, percentage was applied. Other inferential statistical tests like Chi
      square, Fisher's-exact test and one-way ANOVA was applied to find out the
      association of CD66c with different stages. The difference were interpreted as
      statistically significant when p <0.05. RESULTS: CD66c showed differential
      expression with membrane positivity in normal colorectal epithelial cells and
      cytoplasmic expression in tumour cells. There was significant correlation between
      CD66c expression and tumour site (p=0.02) with colon carcinoma showing positive
      expression compared to the rectal carcinoma. There was no significant correlation
      between CD66c staining and tumour stage (p=0.947). No significant relationship
      was observed between CD66c expression and other clinicopathologic variables
      studied such as sex (p=0.552), age (p=0.713) and tumour grade (p=0.263).
      CONCLUSION: CD66c can be specifically used for colon carcinoma and may be a novel
      marker in colon carcinoma stem cell isolation. The quantification of CD66c can be
      further verified by flow cytometry and RT-PCR. Further studies can be carried out
      using CD66c alone or in combination with other markers to develop cancer stem
      cell directed therapy.

PMID- 27042568
TI  - Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors
      and Prognostic Significance.
AB  - INTRODUCTION: Intraoperative management of thyroid gland in laryngeal and
      hypopharyngeal cancer is controversial. AIM: The objectives of this study were to
      determine the incidence of thyroid gland invasion in patients undergoing surgery
      for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to
      assess the prognosis in patients with and without thyroid gland invasion.
      MATERIALS AND METHODS: One hundred and thirty-three patients who underwent
      surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed
      retrospectively. Surgical specimens were examined to determine the incidence of
      thyroid gland invasion and predictive factors were analysed. The recurrence rate
      and the survival in patients with and without thyroid gland invasion were also
      analysed. RESULTS: Out of the 133 patients with carcinoma larynx and hypopharynx
      who underwent surgery, histological thyroid gland invasion was observed in 28/133
      (21%) patients. Significant relationship was found between histological thyroid
      gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan
      and also when gross thyroid gland involvement observed during surgery. There is
      significant association between thyroid gland invasion when there is upper
      oesophageal or subglottic involvement. CONCLUSION: After analysing the
      retrospective data from our study, we would like to suggest that thyroid gland
      need not be removed routinely in all laryngectomies, unless there is advanced
      disease with thyroid cartilage erosion and gross thyroid gland involvement or
      disease with significant subglottic or oesophageal involvement.

PMID- 27042569
TI  - Non-Functional Paraganglioma of the Urinary Bladder Treated by Transurethral
      Resection: Report of Two Cases.
AB  - Paraganglioma of the urinary bladder is a rare tumour derived from chromaffin
      tissue of the sympathetic nervous system. Paraganglioma of the urinary bladder
      especially the non-functional type is often misdiagnosed as urothelial cancer.
      Two female patients aged 32 years and 45 years presented with painless haematuria
      without any symptoms of catecholamine excess. Radiological investigations
      revealed urinary bladder tumour. The tumour was removed by transurethral
      resection in both the patients. Histopathological diagnosis was paraganglioma,
      which was confirmed by immunohistochemistry. Complete resection of tumour by
      transurethral approach is curative in paraganglioma of the urinary bladder. We
      hereby, also discuss the salient features of nonfunctional paraganglioma of the
      urinary bladder. 

PMID- 27042570
TI  - Recurrent Primary Angiosarcoma of the Breast Presenting as Kasabach-Merritt
      Syndrome: A Case Report and Review of Literature.
AB  - Angiosarcoma of the breast is an unusual tumour. The diagnosis of this condition
      is difficult clinically, pathologically and radiologically. Treatment includes
      surgery followed by chemoradiation. The tumour is notorious for its recurrence
      and is generally associated with poor prognosis. Kasabach-Merritt syndrome also
      is a very rare entity seen primarily in infants with vascular malformations and
      carries a poor prognosis. In this report, the authors describe a patient with
      recurrent primary angiosarcoma of the breast, which presented as Kasabach-Merritt
      syndrome. 

PMID- 27042571
TI  - Association of Genital Infections Other Than Human Papillomavirus with Pre
      Invasive and Invasive Cervical Neoplasia.
AB  - Human papillomavirus (HPV) is a well-established causative agent of malignancy of
      the female genital tract and a common Sexually Transmitted Infection. The
      probable co-factors that prevent spontaneous clearance of HPV and progression to
      neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas
      vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory
      conditions can lead to pre-neoplastic manifestations in the cervical epithelium;
      however their specific role in cervical carcinogenesis is not yet established.
      Therefore it is imperative to study the likely association between HPV and co
      infection with various common pathogens in the genital tract of women having
      cervical precancer or cancer. A "Pubmed" search was made for articles in
      Literature on this topic using the words: Cervical neoplasia, HPV, co-infections,
      Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida,
      Chlamydia and the relevant information obtained was used to draft the review. 

PMID- 27042572
TI  - Hypertonic Dextrose Injection for The Treatment of a Baker's Cyst.
AB  - We present extremely rare and interesting case of a Baker's cyst treated with
      hypertonic dextrose injection. A 54-year-old female patient had a Baker's cyst
      which was diagnosed by an ultrasonography. After the failure of the two-weekly
      conservative treatment, we injected hypertonic dextrose (25%) into her right knee
      joint for the treatment of a Baker's cyst. Two weeks after the injection, the
      patient reported improvement in posterior knee pain, and an US showed a
      resolution of the posterior knee cyst. Certainly hypertonic dextrose injection
      for the treatment of a Baker's cyst appears to be a reasonable treatment option.
      Further studies are needed in order to elucidate the efficacy of hypertonic
      dextrose injection in the treatment of Baker's cysts. 

PMID- 27042573
TI  - Eccentric Training as an Adjunct to Rehabilitation Program for Hereditary
      Multiple Exostoses: A Case Report.
AB  - Hereditary multiple exostoses an autosomal dominant skeletal disorder
      characterized by multiple cartilage-capped benign exostoses that typically occur
      in the metaphysis of long bones. The prevalence of hereditary multiple exostoses
      is estimated to be 1 in 50,000. Although, there have been many studies concerning
      this rare disorder, no research has yet examined the rehabilitation of hereditary
      multiple exostoses. The case diagnosed with hereditary multiple exostoses
      referred to our department with several complaints, namely pain, joint
      limitations, muscle weakness, and functional insufficiency after arthroscopic
      distal left femur exostoses excision. The aim of this case report was to present
      effectiveness of eccentric training as an adjunct to rehabilitation program for
      hereditary multiple exostoses. According to the results, eccentric training after
      arthroscopic exostoses excision may help reduce pain, increase range of motion,
      muscle strength, and functional levels in patients with hereditary multiple
      exostoses. 

PMID- 27042574
TI  - Evaluation of the Secretor Status of ABO Blood Group Antigens in Saliva among
      Southern Rajasthan Population Using Absorption Inhibition Method.
AB  - INTRODUCTION: The ABO blood group system was the significant element for forensic
      serological examination of blood and body fluids in the past before the wide
      adaptation of DNA typing. A significant proportion of individuals (80%) are
      secretors, meaning that antigens present in the blood are also found in other
      body fluids such as saliva. Absorption inhibition is one such method that works
      by reducing strength of an antiserum based on type and amount of antigen present
      in the stains. AIM: To check the efficacy of identifying the blood group antigens
      in saliva and to know the secretor status using absorption inhibition method
      among southern Rajasthan population. MATERIALS AND METHODS: Blood and saliva
      samples were collected from 80 individuals comprising 20 individuals in each
      blood group. The absorption inhibition method was used to determine the blood
      group antigens in the saliva and then the results were correlated with the blood
      group of the collected blood sample. The compiled data was statistically analysed
      using chi-square test. RESULTS: Blood groups A & O revealed 100% secretor status
      for both males and females. While blood groups B and AB revealed 95% secretor
      status. CONCLUSION: Secretor status evaluation of the ABO blood group antigen in
      saliva using absorption inhibition method can be a useful tool in forensic
      examination.

PMID- 27042575
TI  - Qualitative Analysis of Collagen Fibers in Oral Submucous Fibrosis using
      Picrosirius Red Stain and Polarising Microscope.
AB  - INTRODUCTION: Oral Submucous Fibrosis (OSMF) is an oral potentially malignant
      condition caused predominantly by areca nut chewing. Early recognition with
      accurate staging of the disease and appropriate treatment planning is of utmost
      importance to prevent the malignant transformation and to improve the quality of
      life of the patient. Picrosirius red stain is specific for collagen and enhances
      its birefringence under polarising light producing different colours in different
      stages of the disease. AIM: To compare the clinical and functional staging with
      histopathologic staging methods used to assess the severity of OSMF and to
      perform a qualitative analysis of the collagen fibres in various histopathologic
      stages of OSMF using picrosirius red stain and polarising microscope. MATERIALS
      AND METHODS: It is a retrospective study done on archival samples. The study
      sample included a total of 30 cases which was divided into two groups. Group I
      comprised of 20 OSMF samples and Group II comprised of 10 normal tissue samples.
      Clinical, functional and histopathological staging was performed for all OSMF
      samples. Comparative analysis between clinical and functional stages with the
      histopathological staging was done using chi square test. Picrosirius red-
      stained sections of OSMF were analysed using polarising microscopy to evaluate
      the qualitative changes in the collagen fibers. STATISTICAL ANALYSIS USED:
      Descriptive data which includes frequency and percentages were calculated for
      each group. Categorical data were analysed by chi-square test. A p-value of 0.05
      or less was considered statistically significant. RESULTS: Comparative analysis
      between clinical and functional stages with the histopathological staging
      revealed a significant correlation (p < 0.05) between the functional and
      histopathological stage. Enhanced birefringence of the collagen fibers due to
      picrosirius red stain yielded characteristic prominent polarising colours in
      different stages of OSMF. CONCLUSION: Comparison of functional staging with
      histopathologic grading is more reliable in determining the severity of the
      disease than the clinical staging. Production of characteristic polarising
      colours by various stages of picrosirius red stained sections of OSMF
      substantiates the use of picrosirius red stain and polarising microscope as a
      tool in assessing the severity of this condition thereby aiding in better
      treatment planning.

PMID- 27042576
TI  - Efficacy of Photodynamic Therapy and Lasers as an Adjunct to Scaling and Root
      Planing in the Treatment of Aggressive Periodontitis - A Clinical and
      Microbiologic Short Term Study.
AB  - INTRODUCTION: Aggressive periodontitis comprises a group of rare, severe, rapidly
      progressive form of periodontitis. Conventional treatment includes mechanical
      debridement augmented with adjunctive antimicrobial therapy. Development of
      antibiotic resistance has led to use of lasers. Photodynamic therapy (PDT) is a
      novel non-invasive therapeutic approach with increased site and pathogen
      specificity. This study compares PDT and Lasers as an adjunct to conventional
      Scaling in the treatment of patients with aggressive periodontitis. MATERIALS AND
      METHODS: Fifteen untreated aggressive periodo-ntitis patients were randomly
      assigned in a split mouth design for one of the following treatment modalities:
      1) SRP alone; (2) SRP + Diode Laser irradiation with 810 nm at 1W, continuous
      mode for 30 sec per tooth; (3) SRP + PDT on "0" day; (4) SRP + PDT on "0", 7(th)
      and 21(st) day. The clinical parameters included PI, BOP, PPD, CAL recorded at
      the baseline & 3(rd) month. The site with greatest probing pocket depth (PPD) was
      selected from each quadrant for bacterial sampling and cultured for
      Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis & Prevotella
      intermedia. RESULTS: Statistically significant reduction in clinical & microbial
      parameters was seen. Sites 4 showed a greater reduction compared to other groups.
      CONCLUSION: Photodynamic therapy is a valuable treatment modality adjunctive to
      conventional scaling and root planing.

PMID- 27042577
TI  - Effect of Probiotic Curd on Salivary pH and Streptococcus mutans: A Double Blind
      Parallel Randomized Controlled Trial.
AB  - BACKGROUND: Dairy products like curd seem to be the most natural way to ingest
      probiotics which can reduce Streptococcus mutans level and also increase salivary
      pH thereby reducing the dental caries risk. OBJECTIVES: To estimate the role of
      probiotic curd on salivary pH and Streptococcus mutans count, over a period of 7
      days. MATERIALS AND METHODS: This double blind parallel randomized clinical trial
      was conducted at the institution with 60 caries free volunteers belonging to the
      age group of 20-25 years who were randomly allocated into two groups. Test Group
      consisted of 30 subjects who consumed 100ml of probiotic curd daily for seven
      days while an equal numbered Control Group were given 100ml of regular curd for
      seven days. Saliva samples were assessed at baseline, after 1/2 hour 1 hour and 7
      days of intervention period using pH meter and Mitis Salivarius Bacitracin agar
      to estimate salivary pH and S. mutans count. Data was statistically analysed
      using Paired and Unpaired t-test. RESULTS: The study revealed a reduction in
      salivary pH after 1/2 hour and 1 hour in both the groups. However after 7 days,
      normal curd showed a statistically significant (p< 0.05) reduction in salivary pH
      while probiotic curd showed a statistically significant (p< 0.05) increase in
      salivary pH. Similarly with regard to S. mutans colony counts probiotic curd
      showed statistically significant reduction (p< 0.05) as compared to normal curd.
      CONCLUSION: Short-term consumption of probiotic curds showed marked salivary pH
      elevation and reduction of salivary S. mutans counts and thus can be exploited
      for the prevention of enamel demineralization as a long-term remedy keeping in
      mind its cost effectiveness.

PMID- 27042578
TI  - The Oral Carriage of Candida in Oral Cancer Patients of Indian Origin Undergoing
      Radiotherapy and/or Chemotherapy.
AB  - INTRODUCTION: Oral cancer is a challenging disease in Indian subcontinent because
      of increased use of tobacco and associated products. Although surgery is the main
      treatment modality, radiotherapy (RT) and chemotherapy (CT) are employed in
      inaccessible cases. Both RT & CT will result in painful and debilitating adverse
      effects in oral cavity e.g., mucositis, ulceration, dysgeusia, xerostomia and
      opportunistic infections. One of the most common opportunistic infection is
      caused by fungus Candida. AIM: Our aim was to investigate the incidence of oral
      colonization of Candida species with differentiation between carrier and
      infective state of the organism. We also investigate the effect of treatment
      modality (RT and CT) on the incidence of Candida, in oral cancer patients,
      undergoing RT and/or CT, in order to prevent and treat the Candida infection in a
      better way. MATERIALS AND METHODS: It was a cross-sectional case-control study;
      done in Gujarat, India. Fifty patients of oral cancer undergoing RT, CT alone or
      combined were investigated and compared with the healthy controls. The samples
      were collected from mid-dorsum of tongue by using imprint culture technique. The
      samples were inoculated on Sabouraud's dextrose agar medium and the organisms
      were identified by wet mount, germ tube test, chlamydospore formation and sugar
      fermentation tests. RESULTS: There was significant increase in oral Candida
      colonization from 20% in healthy controls to 70% in oral cancer patients
      undergoing RT and/or CT (p = 0.001, < 0.05). A significant increase in infective
      state of Candida (71.4%) was noted (p = 0.001, < 0.05) with predominance of non
      albicans species of Candida, chiefly C. tropicalis (42.8%). CONCLUSION: RT and CT
      leads to increased oral colonization and infection by Candida with a shift
      towards growth of non-albicans species. As the pattern of candidal species
      infection is changing, such studies are important for better diagnosis and
      treatment planning to gain good control over the disease.

PMID- 27042579
TI  - Anterior Ridge Extension Using Modified Kazanjian Technique in Mandible- A
      Clinical Study.
AB  - INTRODUCTION: Good alveolar ridge is a prerequisite for successful conventional/
      implant supported partial/complete denture. Extensively resorbed ridges with
      shallow vestibule and high insertion of muscles in to the ridge crest, leads to
      failure of prosthesis. Success of prosthesis depends on surgical repositioning of
      mucosa and muscle insertions, which increases the depth of vestibule and denture
      flange area for retention. So, the study was planned to provide good attached
      gingiva with adequate vestibular depth using Modified Kazanjian Vestibuloplasty
      (MKV). AIM: To evaluate efficacy of MKV technique for increasing vestibular depth
      in anterior mandible so that successful prosthesis can be delivered. Efficacy of
      the technique was evaluated through operating time required, vestibular depth
      achieved, scarring or relapse and any postoperative complications associated with
      the healing. MATERIALS AND METHODS: Total of 10 patients were included in the
      study, who had minimum 20mm of bone height and less than 5mm of vestibular depth
      for MKV procedure. The results were tabulated and statistical analysis was
      carried out to assess vestibular depth achieved i.e. from crest of the ridge to
      junction of attached mucosa both pre and postoperatively. The study results were
      compared with existing literature. RESULTS: Healing of raw surface was uneventful
      with satisfactory achievement of vestibular depth. The average gain in vestibular
      depth was 11 mm. The patients had good satisfaction index for prosthesis.
      CONCLUSION: Even in the era of implant prosthesis Modified Kazanjian technique is
      worth to practice to achieve good results and overcorrection is not required as
      that of standard Kazanjian technique. It provides adequate attached gingiva for
      successful prosthesis. Extension of vestibular depth enables fabrication of
      better denture flange with improved oral hygiene. This technique does not require
      hospitalization and additional surgery for grafts.

PMID- 27042580
TI  - Effect of Oral Premedication on the Efficacy of Inferior Alveolar Nerve Block in
      Patients with Symptomatic Irreversible Pulpitis: A Prospective, Double-Blind,
      Randomized Controlled Clinical Trial.
AB  - INTRODUCTION: It is generally accepted that achieving complete anaesthesia with
      an Inferior Alveolar Nerve Block (IANB) in mandibular molars with symptomatic
      irreversible pulpitis is more challenging than for other teeth. Therefore,
      administration of Non-Steroidal Anti-Inflammatory Agents (NSAIDs) 1 hour prior to
      anaesthetic administration has been proposed as a means to increase the efficacy
      of the IANB in such patients. AIM: The purpose of this prospective, double-blind,
      randomized clinical trial was to determine the effect of administration of oral
      premedication with ketorolac (KETO) and diclofenac potassium (DP) on the efficacy
      of IANB in patients with irreversible pulpitis. MATERIALS AND METHODS: One
      hundred and fifty patients with irreversible pulpitis were evaluated
      preoperatively for pain using Heft Parker visual analogue scale, after which they
      were randomly divided into three groups. The subjects received identical tablets
      of ketorolac, diclofenac pottasium or cellulose powder (placebo), 1 hour prior to
      administration of IANB with 2% lidocaine containing 1:200 000 epinephrine. Lip
      numbness as well as positive and negative responses to cold test were
      ascertained. Additionally pain score of each patient was recorded during cavity
      preparation and root canal instrumentation. Success was defined as the absence of
      pain or mild pain based on the visual analog scale readings. The data was
      analysed using One-Way Anova, Post-Hoc Tukey pair wise, Paired T - Test and chi
      square test. Trial Registery Number is 4722/2015 for this clinical trial study.
      RESULTS: There were no significant differences with respect to age (p =0.098),
      gender (p = 0.801) and pre-VAS score (DP-KETO p=0.645, PLAC-KETO p =0.964, PLAC
      DP p = 0.801) between the three groups. All patients had subjective lip
      anaesthesia with the IAN blocks. Patients of all the three groups reported a
      significant decrease in active pain after local anaesthesia (p< 0.05). The post
      injection VAS Score was least in group 1 (KETO) followed by group II (DP) &
      maximum in group III (PLACEBO). CONCLUSION: Oral pre-medication with 10 mg KETO
      resulted in significantly higher percentage of successful inferior alveolar block
      in patients with irreversible pulpitis than pre-medication with 50 mg DP & PLAC.

PMID- 27042581
TI  - Versitality of the Use of Collagen Membrane in Oral Cavity.
AB  - INTRODUCTION: Bovine derived collagen membrane is usually and regularly used as a
      temporary cover or dressing for the extra oral wounds and for the burns on the
      body. It has wide applications because of its usefulness and biocompatibility.
      This has provoked us to do a study with the use of collagen membrane even for the
      intraoral minor surgical defects. AIM: The study was conducted to evaluate the
      clinical efficacy of collagen membrane as a biological dressing material for
      intraoral wounds, to check for haemostasis, pain control, granulation tissue
      formation, rapid re-epithelialization and minimal contracture. MATERIALS AND
      METHODS: A total of 30 patients 19 male, 11 female were taken for excision of
      various intraoral lesions like leukoplakia patches, mucocele, epulis growths,
      irritational fibroma, frenectomy and the surgical defects were closed with
      collagen membrane. Postoperatively healing was assessed by taking five clinical
      parameters of Haemostasis, Pain, Granulation tissue, Epithelialization,
      Contracture. RESULTS: Among 30 patients, haemostasis score was found to be good
      in 28 cases, fair in two cases. Pain relief score was good in seven cases, fair
      in 19 cases, poor in four cases. Granulation tissue formation score was good in
      eight cases, fair in 13 cases, poor in nine cases. Epithelialization score was
      good in 19 cases, fair in seven cases, poor in four cases. Contracture score was
      good in six cases, fair in 16 cases, poor in eight cases. Total score of all the
      five parameters, which was rated as effectiveness score, was calculated by using
      a standard scale. Final scoring was very effective in six cases, effective in 20
      cases, ineffective in four cases. CONCLUSION: Reconstituted bovine derived
      collagen membrane used in our study was found to be an effective intraoral wound
      dressing material for faster uneventful healing of intraorally also.

PMID- 27042582
TI  - Salivary Lactate Dehydrogenase (LDH)- A Novel Technique in Oral Cancer Detection
      and Diagnosis.
AB  - INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the sixth most common
      malignancy which is a major cause for cancer morbidity and mortality worldwide.
      Early diagnosis and intervention improves the overall survival rate. AIM: The
      current study was done to evaluate the accuracy of salivary LDH as a potential
      biomarker for diagnosis of OSCC and to correlate the levels of salivary LDH with
      the histological differentiation of the tumour. MATERIALS AND METHODS: Thirty
      patients visiting the outpatient department diagnosed clinically and
      histologically with OSCC were selected for the study with a control group of 20
      patients. Unstimulated salivary samples collected from the selected patients were
      centrifuged and processed. Readings of enzyme activity in the salivary samples
      was established through auto analysis using International Federation of Clinical
      Chemistry (IFCC) method. Levels of the enzyme activity in both the control and
      the study group were compared and statistically analysed using student t-test.
      The three subgroups were also compared and statistically analysed. RESULTS: The
      results showed a mean value of 497.00 with a SD of 51.75 among the control group
      and a mean value of 1225.40 with a SD of 221.79 among the cases with a p-value of
      0.0001 which was statistically significant. Furthermore, when the LDH values for
      the various grades of OSCC were compared, the mean values were 1049.07, 1309.50
      and 1586.20 respectively, for well differentiated, moderately differentiated and
      poorly differentiated carcinoma. CONCLUSION: The p-value thus obtained revealed
      LDH values which were significantly higher in patients with OSCC and furthermore
      the levels significantly correlated with the histopathological grade of the
      tumour.

PMID- 27042583
TI  - Clinicopathologic Correlation of White, Non scrapable Oral Mucosal Surface
      Lesions: A Study of 100 Cases.
AB  - INTRODUCTION: White, non scrapable lesions are commonly seen in the oral cavity.
      Based on their history and clinical appearance, most of these lesions can be
      easily diagnosed, but sometimes diagnosis may go wrong. In order to arrive to a
      confirmative diagnosis, histopathological assessment is needed in many cases, if
      not all. AIMS: 1) To find out the prevalence of clinically diagnosed oral white,
      non scrapable lesions. 2) To find out the prevalence of histopathologically
      diagnosed oral white, non scrapable lesions. 3) To correlate the clinical and
      histopathological diagnosis in the above lesions. MATERIALS AND METHODS: A total
      of 100 cases of oral white, non scrapable lesions were included in the study.
      Based on their history and clinical presentation, clinical provisional diagnosis
      was made. Then biopsy was done and confirmatory histopathological diagnosis was
      given and both were correlated. In order to correlate clinical and
      histopathological diagnosis Discrepancy Index (DI) was calculated for all the
      cases. RESULTS: Based on clinical diagnosis, there were 59 cases (59%) of
      leukoplakia, 29 cases (29%) of lichen planus and six cases (6%) of lichenoid
      reaction; whereas, based on histopathological diagnosis, there were 66 cases
      (66%) of leukoplakia epithelial hyperplasia and hyperkeratosis (leukoplakia) and
      30 cases (30%) of lichen planus. Seventy eight clinically diagnosed cases (78%)
      correlated with the histopathological diagnosis and 22 cases (22%) did not
      correlate. The total discrepancy index was 22%. CONCLUSION: A clinician needs to
      be aware of oral white, non scrapable lesions. Due to the overlapping of many
      clinical features in some of these lesions and also due to their malignant
      potential, a histopathological confirmative diagnosis is recommended.

PMID- 27042584
TI  - Commercial and Plant Extract Denture Cleansers in Prevention of Candida albicans
      Growth on Soft Denture Reliner: In Vitro Study.
AB  - OBJECTIVE: To evaluate and compare the efficacy of two plant extracts and two
      commercially available denture cleansers against candida albicans adherent to
      soft denture reline material. MATERIALS AND METHODS: In this study 60 specimens
      of soft denture reliner material specimens were fabricated with dimensions
      10x10x2 mm. The sterile specimens were inoculated by immersion in Sabourand broth
      containing Candida albicans for 16 hours at 37 degrees C in an incubator. Then
      the specimens were washed and immersed in denture cleansers which were divided
      into group five groups from Group I-V for CD Clean((r)), Nigella sativa, thyme
      essential oil, Fittydent((r)) and distilled water respectively, for 8 hours at
      room temperature. Then they were washed, fixed with methanol and stained with
      crystal violet. Candida cells adherent to the specimens were counted under
      microscope. The number of cells adherent to test samples were compared with that
      adherent to control. RESULTS: The effectiveness of Fittydent((r)) was more than
      CD Clean((r)) in reducing the adherent candida albicans and the difference was
      statically significant (p = <0.001). Both thyme essential oil and nigella sativa
      were almost same in effectiveness against candida albicans but the difference was
      not statically significant (p= 0.79). Post-hoc Tukey's test was performed which
      indicated that Fittydent(r) was the most effective amongst the denture cleansers
      tested in this study, followed by thyme essential oil, nigella sativa and CD
      Clean((r)). CONCLUSION: The results of the study showed that all denture
      cleansers used in the study were significantly effective. The study indicated
      that Fittydent is more effective amongst the denture cleansers because of its
      mechanism of action; however the plant extracts used in this study were also
      significantly effective against candida albicans.

PMID- 27042585
TI  - Evaluation of the Stress Induced in Tooth, Periodontal Ligament & Alveolar Bone
      with Varying Degrees of Bone Loss During Various Types of Orthodontic Tooth
      Movements.
AB  - INTRODUCTION: The force applied on to a tooth with periodontal bone loss may
      generate different magnitude and pattern of stresses in the periodontium when
      compared to a tooth with no bone loss & under the same force system. The
      intensity of the forces and moment to force ratios needed to be applied during an
      Orthodontic treatment must be adapted to obtain the same movement as in a tooth
      with a healthy periodontal support. AIM: Evaluation and assessment of the stress
      distribution during various types of Orthodontic tooth movement on application of
      Orthodontic force, at various levels of alveolar bone loss; & determination of
      the most ideal force system producing the Optimum Stress (i.e., stress within
      optimum range), uniformly (conducive to bodily movement of maxillary canine with
      varying degrees of bone loss). MATERIALS AND METHODS: A human maxillary canine
      tooth of right side was simulated by means of Finite Element Method (FEM). Five
      different models were constructed with bone loss ranging from 0mm in model 1, to
      8mm in model 5 (progressing at 2mm per model). Ten different loading conditions
      were applied on these models and the stress generated was charted at various
      occluso-gingival levels and surfaces around the tooth. The evaluation and
      assessment of the stress distribution during various types of Orthodontic tooth
      movement on application of Orthodontic force, at various levels of alveolar bone
      loss was done. RESULTS: The results showed that there was a high positive
      correlation between the increase in bone loss & the stress generated, suggesting
      an elevation in the stress with advancing bone loss. Additionally, the type of
      tooth movement was found to be changed with bone loss. During the determination
      of ideal force system it was found that the centre of resistance of the canine
      migrated apically with bone loss and an increase in the moment to force ratio
      (Mc:F) was required to control the root position in these cases. CONCLUSION: A
      high positive correlation exists between the increase in bone loss and the stress
      generated. Suitable modification should be done in the force system under bone
      loss conditions.

PMID- 27042586
TI  - Comparative Evaluation of Fluoride Recharge Ability of Conventional and
      Hydroxyapatite Modified Glass Ionomer Cement with Daily Low Fluoride Exposure- An
      Invitro Study.
AB  - INTRODUCTION: Glass ionomer cement (GIC) has best suited paediatric dentists and
      is well recognised in the preventive era of dentistry. However its use is
      affected by its inferior mechanical properties. Hydroxyapatite whiskers have been
      lately introduced as strengthening additive without affecting its fluoride
      releasing property, but literature lacks data related to its effect on recharging
      ability of glass ionomer cement. AIM: To evaluate and compare fluoride release
      from hydroxyapatite incorporated glass ionomer cement following recharging with
      low fluoride dentifrices. MATERIALS AND METHODS: An 8% Hydroxyapatite whiskers
      were added to Conventional Glass ionomer powder and 40 specimens each of
      conventional and Hydroxyapatite Glass ionomer cement were prepared using
      customised Teflon mould (5mm x 2mm) and were suspended in deionised water.
      Recharging of aged specimens was done using low fluoridated dentifrices
      containing 500ppm fluoride, twice daily and water was replenished every 24 hours.
      Fluoride release was analysed daily for 7 days and then weekly till 21 days using
      Sension 4 pH/ion selective electrode. Data thus obtained was statistically
      analysed by descriptive analysis followed by repeated measures ANOVA. RESULTS:
      Significant (p<0.01) increase in fluoride release was observed in both the
      materials following recharging regimen. Recharge pattern of hydroxyapatite glass
      ionomer was found to be similar to conventional glass ionomer cement. CONCLUSION:
      Within the limitations of this study it can be evinced that fluoride
      rechargability and re-release remains unaffected by the addition of
      hydroxyapatite whiskers and hence proves to be more acceptable additive to glass
      ionomer cement to improve its mechanical properties widening its arena of usage
      by clinicians.

PMID- 27042587
TI  - Dimensional Accuracy of Hydrophilic and Hydrophobic VPS Impression Materials
      Using Different Impression Techniques - An Invitro Study.
AB  - INTRODUCTION: The dimensional stability of the impression material could have an
      influence on the accuracy of the final restoration. Vinyl Polysiloxane Impression
      materials (VPS) are most frequently used as the impression material in fixed
      prosthodontics. As VPS is hydrophobic when it is poured with gypsum products,
      manufacturers added intrinsic surfactants and marketed as hydrophilic VPS. These
      hydrophilic VPS have shown increased wettability with gypsum slurries. VPS are
      available in different viscosities ranging from very low to very high for usage
      under different impression techniques. AIM: To compare the dimensional accuracy
      of hydrophilic VPS and hydrophobic VPS using monophase, one step and two step
      putty wash impression techniques. MATERIALS AND METHODS: To test the dimensional
      accuracy of the impression materials a stainless steel die was fabricated as
      prescribed by ADA specification no. 19 for elastomeric impression materials. A
      total of 60 impressions were made. The materials were divided into two groups,
      Group1 hydrophilic VPS (Aquasil) and Group 2 hydrophobic VPS (Variotime). These
      were further divided into three subgroups A, B, C for monophase, one-step and two
      step putty wash technique with 10 samples in each subgroup. The dimensional
      accuracy of the impressions was evaluated after 24 hours using vertical profile
      projector with lens magnification range of 20X-125X illumination. The study was
      analyzed through one-way ANOVA, post-hoc Tukey HSD test and unpaired t-test for
      mean comparison between groups. RESULTS: Results showed that the three different
      impression techniques (monophase, 1-step, 2-step putty wash techniques) did cause
      significant change in dimensional accuracy between hydrophilic VPS and
      hydrophobic VPS impression materials. One-way ANOVA disclosed, mean dimensional
      change and SD for hydrophilic VPS varied between 0.56% and 0.16%, which were low,
      suggesting hydrophilic VPS was satisfactory with all three impression techniques.
      However, mean dimensional change and SD for hydrophobic VPS were much higher with
      monophase, mere increase for 1-step and 2-step, than the standard steel die
      (p<0.05). Unpaired t-test displayed that hydrophilic VPS judged satisfactory
      compared to hydrophobic VPS among 1-step and 2-step impression technique.
      CONCLUSION: Within the limitations of this study, it can be concluded that
      hydrophilic Vinyl polysiloxane was more dimensionally accurate than hydrophobic
      Vinyl polysiloxane using monophase, one step and two step putty wash impression
      techniques under moist conditions.

PMID- 27042588
TI  - Orientation of Dental Professionals in India towards Integrative Medicine: A
      Cross-Sectional Survey.
AB  - INTRODUCTION: There is a growing demand on our health care system, including
      Dentistry, to shift from a bio-medical approach to Integrative model of care. The
      attitudes of health professionals towards Integrative Medicine (IM) are an
      important factor that influences this transition. AIM: The aim of this study was
      to evaluate and compare the orientation of the dental professionals in India
      towards the principles and practice of Integrative Medicine. MATERIALS AND
      METHODS: A cross-sectional survey was conducted on 286 dental faculty and
      postgraduate students from three dental schools in India. The participants
      voluntarily and anonymously completed the "Integrative Medicine-30'
      questionnaire, a 30 item self-report instrument that measures the health care
      provider's orientation towards Integrative Medicine in five subscales. Data
      analysis included summary statistics and intergroup comparisons by gender and
      professional status with independent samples Mann-Whitney U test. RESULTS: The
      overall orientation of the dental professionals towards IM was almost neutral.
      While the use of learning resources on Complementary and Alternative Medicine was
      lower, they showed a more positive orientation towards patient-centred care.
      Compared to postgraduate students of Dentistry, the dental faculty were more
      oriented towards IM (median score of 82 vs. 79.5, p<0.01), especially in terms of
      learning from alternate paradigms (14 vs. 12, p<0.01) and safety of Complementary
      and Alternative Medicine (13 vs. 12, p<0.01). Females scored better than males
      both in terms of overall orientation (82 vs. 78, p<0.01) and towards patient
      centred care (12 vs. 11, p<0.001). CONCLUSION: The results highlight the
      impending need to improve the orientation of dental professionals in India
      towards the principles and practice of IM.

PMID- 27042589
TI  - Burnout and Work Engagement Among Dental Practitioners in Bangalore City: A Cross
      Sectional Study.
AB  - INTRODUCTION: Burnout is a job-related stress reaction; a potential hazard for
      personal, professional lives of dentists. Work Engagement (WE) is the antithesis
      of Burnout and they can co-exist. AIM: This study was taken up to know the
      prevalence of Burnout and WE among dentists in Bangalore, India. MATREIALS AND
      METHODS: In a cross-sectional study, all (n=116) dentists practicing in Bangalore
      East Zone were randomly selected. A structured, self-administered questionnaire
      revealing dentists' demographics, practice characteristics, Burnout level [6-item
      from Maslach Burnout Inventory] and WE [4-item from Utrecht Work Engagement
      Scale] was used. Ethical clearance and informed consent was obtained. The data
      was analyzed using SPSS version 15.0. RESULTS: With a response rate of 58.6%,
      high burnout was seen in 5.15% dentists. Personal Accomplishment was
      significantly associated with dentists in older age-group (p=0.002), married
      (p=0.014), MDS qualified (p=0.038), having long working hours (p=0.009) with
      assistants (p=0.024), more years into practice (0.007), travelling more distance
      from residence (p=0.021). Significance was also seen for dedication among
      dentists with assistants (p=0.006), emotional exhaustion among dentist with long
      working hours (p=0.009), and driving own vehicle (p=0.028). Finally absorption
      was found significant in dentists practicing solo. CONCLUSION: Higher WE were
      found but still burnout persisted. Thus, burnout and WE were found to co-exist.

PMID- 27042590
TI  - Prevalence of Tooth Shade and its Correlation with Skin Colour - A Cross
      sectional Study.
AB  - INTRODUCTION: Aesthetics has become an important issue in modern society. Tooth
      shade is one of the factors in determining aesthetics. Studies have revealed that
      tooth shade is influenced by age, gender, eye colour, skin colour and other
      factors. AIM: The present study was aimed to assess the prevalence of tooth shade
      and its correlation with skin colour. MATERIALS AND METHODS: A total of 300
      subjects aged 18-20 years were evaluated for tooth shade using Vitapan - 3D shade
      guide. Anterior teeth were checked under natural light and facial skin colour by
      Lakme liquid foundation make up as a shade guide. Data was analysed using chi
      square test and spearman's correlation. RESULTS: Out of 300 students, 114
      (38.00%) had A2 tooth shade; the least prevalent tooth shade among Chitradurga
      population was C1 (4.00%). There was a positive correlation between tooth shade
      and skin colour which was found to be statistically significant (p <0.05).
      CONCLUSION: The most prevalent tooth shade among Chitradurga population was A2
      and least was C1. There was a significant correlation between tooth shade and
      skin colour with lighter skin tone subjects having lighter tooth shade hence skin
      colour can be used as a guide for shade selection.

PMID- 27042591
TI  - Endodontic Management of a Mandibular Incisor Exhibiting Concurrence of Fusion,
      Talon Cusp and Dens Invaginatus using CBCT as a Diagnostic Aid.
AB  - Teeth with aberrant anatomy present a challenge to the endodontist. Advanced
      tools like cone beam computed tomography aid in exploring the details of
      endodontic architecture in such cases. The aim of this case report is to
      highlight the advantage of CBCT in endodontic management of teeth with multiple
      dental anomalies. A mandibular lateral incisor associated with an extraoral sinus
      tract revealed unusual clinical anatomy. A provisional diagnosis of type III dens
      in dente was made based on radiographic findings. Considering the complex
      anatomy, CBCT was advised to get a confirmatory diagnosis. The anatomic details
      revealed by CBCT differed significantly from the provisional diagnosis. A final
      diagnosis of concurrence of fusion with a supernumerary tooth, talon cusp and
      type II dens invaginatus was established and endodontic treatment of the
      concerned tooth was carried out. Non-surgical endodontic treatment resulted in
      successful resolution of the sinus tract and healing of the periapical lesion.
      CBCT, thus proves to be an excellent diagnostic tool for management of teeth with
      unusual anatomy, paving way for a conservative treatment free of endodontic
      mishaps. 

PMID- 27042592
TI  - Sialocele of Parotid Duct: Report of Case with Review of Literature.
AB  - Parotid duct sialocele is a salivary cavity arising at the expense of parotid
      duct. Facial trauma is the most common cause of this rare condition. If left
      untreated, a sialocele may develop into a significantly large facial swelling.
      Fistula formation may occur, often draining extraorally. We report a case of
      Parotid duct sialocele that was assessed by sialography and ultrasonogarphy and
      was managed by placement of intraductal cannula for fifteen days till duct was
      found patent. We also discuss various treatment options of this condition in this
      case report. 

PMID- 27042593
TI  - Autotransplantation of a Buccally Erupted Matured Mandibular Third Molar to
      Replace a Grossly Decayed Second Molar.
AB  - Autotransplantation can be a treatment option for tooth loss as an alternative to
      fixed or implant-supported prostheses. It has predictable results comparable to
      implants, with reported success rates often greater than 90%. In present case,
      buccally erupted matured third molar was autotransplanted in extraction socket of
      grossly carious mandibular second molar. The tooth was splinted for 1 week
      followed by root canal treatment. After 12 months follow up, tooth was in perfect
      state of function and aesthetic with healthy periapical and periodontal
      architecture. High success rate was found in immature tooth transplantation in
      previous case reports. This case report describes that even matured tooth can
      also be used as donor if atraumatic extraction is possible and endodontic
      treatment is well performed. 

PMID- 27042594
TI  - Spindle Cell Carcinoma of the Mandibular Gingiva - A Case Report.
AB  - Spindle cell carcinoma is a malignancy of epithelial origin often mimicking its
      mesenchymal counterpart thus posing a diagnostic challenge. It is a rare biphasic
      malignant tumour mostly encountered in the upper aerodigestive tract. The chief
      differential diagnoses of spindle cell carcinoma are true superficial sarcomas
      and they especially need to be differentiated from fibrosarcoma. This
      presentation reports a spindle cell carcinoma of the gingiva and highlights the
      difficulties encountered in the diagnosis. It also emphasizes the importance of
      accurate and thorough diagnosis of malignant spindle cell lesions to determine
      the appropriate therapeutic modality. 

PMID- 27042595
TI  - A Rare and Extensive Case of Oral Malignant Melanoma involving Mandibular
      Gingiva.
AB  - Oral malignant melanoma is an infrequent but an aggressive neoplasm of unknown
      etiology, seen most commonly in middle age male patients and is more frequently
      seen at the hard palate and gingiva. The tumor tends to metastasize or locally
      invade tissue more readily than other malignant tumors in the oral region. In
      this article, we report a rare case of extensive oral melanoma in a 55-year-old
      male patient, with a chief complaint of painless growth in mandibular anterior
      gingiva measuring about 2.6 X 1.7 X 0.8 cm and extending bilaterally till
      posterior mandibular gingiva and unilaterally to right buccal mucosa. The most
      common site being hard palate and maxillary gingiva, it is extremely rare in
      mandibular gingiva (less than 7%) and hence, this rare occurrence in mandibular
      gingiva is reported, the diagnosis of which was confirmed by histopathology and
      immunohistochemistry. 

PMID- 27042596
TI  - Rehabilitation of Glossectomy Cases with Tongue Prosthesis: A Literature Review.
AB  - Tongue is the only movable muscular organ without any bone in the human body. It
      has very important role in perception of taste and sensations like touch,
      pressure, heat and cold. The purpose of the article is to review various types of
      tongue prosthesis and their clinical applications. This review helps the
      clinician to choose the appropriate type of tongue prosthesis for different
      clinical situations, retention of tongue prosthesis and material selection for
      each type of prosthesis. A broad search of published literature was performed
      using the keyword glossectomy, glossal prosthesis and tongue prosthesis from 1980
      to 2014 in Medline, Google scholar, internet and text book. This review gives
      basic knowledge of glossal prosthesis and selection of the same for various
      clinical conditions. 

PMID- 27042597
TI  - Paediatric Geographic Tongue: A Case Report, Review and Recent Updates.
AB  - Geographic tongue is a benign recurrent condition of uncertain aetiology
      affecting the tongue characterized by loss of epithelium especially filiform
      papillae giving a characteristic appearance. The clinical presentation may vary
      from asymptomatic to painful and burning ulceration. The condition is commonly
      seen in adults but few cases are reported in children. A case of asymptomatic
      geographic tongue in three-year-old male child and literature review with new
      insight in aetiology is presented here. Management depends on the clinical
      condition and underlying aetiology. 

PMID- 27042598
TI  - Medical Management of Oral Lichen Planus: A Systematic Review.
AB  - INTRODUCTION: Oral Lichen Planus (OLP) is a chronic inflammatory, T-cell-mediated
      autoimmune oral mucosal disease with unclear aetiology. The clinical management
      of OLP poses considerable difficulties to the oral physician. AIM: The aim was to
      assess the efficacy of any form of intervention used to medically manage OLP.
      MATERIALS AND METHODS: We searched and analysed the following databases (from
      January 1990 to December 2014):- Cochrane Oral Health Group Trials Register,
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. All
      Randomised Controlled Trials (RCTs) for the medical management of OLP which
      compared active treatment with placebo or between active treatments were
      considered in this systematic review. Participants of any age, gender or race
      having symptomatic OLP (including mixed forms), unconnected to any identifiable
      cause (e.g. lichenoid drug reactions) and confirmed by histopathology have been
      included. Interventions of all types, including topical treatments or systemic
      drugs of variable dosage, duration & frequency of delivery have been considered.
      All the trials identified were appraised by five review authors and the data for
      all the trials were synthesised using specifically designed data extraction form.
      Binary data has been presented as risk ratios (RR) with 95% confidence intervals
      (CI) and continuous data as mean differences (MD) with 95% CIs. RESULTS: A total
      of 35 RCTs were included in this systematic review on medical management of OLP.
      No strong evidence suggesting superiority of any specific intervention in
      reducing pain and clinical signs of OLP were shown by the RCTs included here.
      CONCLUSION: Future RCTs on a larger scale, adopting standardized outcome
      assessing parameters should be considered.

PMID- 27042599
TI  - Odontogenic Myxoma of Mandible: Report of A Rare Case.

PMID- 27042600
TI  - Images in Medicine: Triplicated Primary Anterior Teeth - A Report of Two Cases.

PMID- 27042601
TI  - Implant - Supported Full Mouth Rehabilitation: A Guided Surgical and Prosthetic
      Protocol.

PMID- 27042602
TI  - A Girl with No Pain: Congenital Insensitivity To Pain and Anhidrosis (HSAN) Type
      IV - A Case Report.

PMID- 27042603
TI  - Laparoscopic Repair of Bochdalek Diaphragmatic Hernia in Adults.
AB  - Bochdalek hernia (BH) is an uncommon form of diaphragmatic hernia. The rarity of
      this hernia and its nonspecific presentation leads to delay in the diagnosis,
      with the potential risk of complications. This review summarizes the relevant
      aspects of its presentation and management, based on the present evidence in the
      literature. A literature search was performed on PubMed, Google Scholar, and
      EMBASE for articles in English on BH in adults. All case reports and series from
      the period after 1955 till January 2015 were included. A total of 180 articles
      comprising 368 cases were studied. The mean age of these patients was 51 years
      (range 15-90 years) with a male preponderance of 57% (211/368). Significantly,
      6.5% of patients were above 70 years, with 3.5% of these being above 80 years.
      The majority of the hernias were on the left side (63%), with right-sided hernias
      and bilateral occurring in 27% and 10%, respectively. Precipitating factors were
      noted in 24%, with 5.3% of them being pregnant. Congenital anomalies were seen in
      11%. The presenting symptoms included abdominal (62%), respiratory (40%),
      obstructive (vomiting/abdominal distension; 36%), strangulation (26%); 14% of
      them were asymptomatic (detected incidentally). In the 184 patients who underwent
      surgical intervention, the surgical approach involved laparotomy in 74 (40.27%),
      thoracotomy in 50 (27.7%), combined thoracoabdominal approach in 27 (14.6%),
      laparoscopy in 23 (12.5%), and thoracoscopic repair in 9 (4.89%). An overall
      recurrence rate of 1.6% was noted. Among these patients who underwent
      laparoscopic repair, 82% underwent elective procedure; 66% underwent primary
      repair, with 61% requiring interposition of mesh or reenforcement with or without
      primary repair. The overall mortality was 2.7%. Therefore, BH should form one of
      the differential diagnoses in patients who present with simultaneous abdominal
      and chest symptoms. Minimal access surgery offers a good alternative with short
      hospital stay and is associated with minimum morbidity and mortality. 

PMID- 27042604
TI  - Stress, Burnout and Coping Strategies in Preclinical Medical Students.
AB  - It is acknowledged that physicians do not seek the same expert aid for themselves
      as they would offer their patients. In their preclinical years, medical students
      appear to espouse comparable behavior. To many, medicine is described as a never
      ending path that places the student under heavy stress and burnout from the
      beginning, leaving him/her vulnerable and with insufficient coping methods.
      Hence, the objective of this study is to 1) explore the prevalence of stress and
      burnout among preclinical medical students, and 2) propose solutions to decrease
      stress and burnout and improve medical education in the preclinical years. A
      detailed scholarly research strategy using Google Scholar, Scopus, Embase,
      MEDLINE and PubMed was implemented to highlight key themes that are relevant to
      preclinical medical students' stress and burnout. Stress varied among different
      samples of medical students and ranged between 20.9% and 90%. Conversely, burnout
      ranged between 27% and 75%. Methods that help in reducing the incidence of stress
      and burnout by promoting strategies that focus on personal engagement,
      extracurricular activities, positive reinterpretation and expression of emotion,
      student-led mentorship programs, evaluation systems, career counseling and life
      coaching should be adopted. 

PMID- 27042605
TI  - Differences in Severity and Outcomes Between Hypertriglyceridemia and Alcohol
      Induced Pancreatitis.
AB  - BACKGROUND: Alcohol and hypertriglyceridemia (HTG) are among the most common
      causes of acute pancreatitis (AP) after gallstones. However, differences in
      severity at the time of presentation and outcomes have not been well-studied.
      OBJECTIVE: The aim of this study is to assess the differences between severity at
      presentation and outcomes of AP of hypertriglyceridemic and alcoholic origins.
      MATERIALS AND METHODS: A retrospective review of 177 patients who were discharged
      with diagnosis of AP was performed. Severity at presentation was identified by
      the presence of systemic inflammatory response syndrome, bedside index for
      severity in AP (BISAP) score, and Balthazar index. Outcomes were measured by the
      length of stay, intensive care unit care, surgical intervention, and mortality.
      RESULTS: We found 147 patients with alcoholic pancreatitis and 30 patients with
      hypertriglyceridemic pancreatitis. A larger percentage of hypertriglyceridemic
      pancreatitis patients (23.33%) had a BISAP score of >=2 compared to the alcoholic
      group (12.24%). Only 32.65% of the patients with alcoholic pancreatitis but 60%
      of the patients with hypertriglyceridemic pancreatitis had the presence of
      systemic inflammatory response syndrome (SIRS) at admission (P = 0.0067). There
      were 73.34% hypertriglyceridemic pancreatits patients and only 40.28% alcoholic
      pancreatitis patients with Balthazar index C or greater, suggesting a higher
      disease burden at admission for hypertriglyceridemic pancreatitis patients (P =
      0.0047). There was a statistically significant difference in the relative number
      of hypertriglyceridemic and alcoholic pancreatitis patients receiving intensive
      care (P = 0.00030) and in receiving surgical interventions related to
      pancreatitis (P = 0.016). CONCLUSION: Our study found that patients with
      hypertriglyceridemic pancreatitis have a greater severity of disease and they
      experience less favorable outcomes than patients with alcoholic pancreatitis.

PMID- 27042606
TI  - Addition of Selenium Improves Immunomodulative Effects of Glucan.
AB  - BACKGROUND: Selenium (Se) is an established essential nutrient that plays a role
      in various biological processes including cancer development. Similarly,
      stimulation of immune reactions by beta-glucans is well-documented. AIMS: In the
      current study, we focused on the stimulation of phagocytosis and interleukin (IL)
      2 production and on potentiation of anticancer immunity by a combination of
      glucan with two types of Se. MATERIALS AND METHODS: Phagocytosis was evaluated
      using synthetic microspheres; cancer development was measured either using breast
      cancer cells or using lung cancer cells. RESULTS: Using two different murine
      models of cancer, we showed that the Se/glucan combination strongly suppressed
      the growth of cancer, mostly probably via stimulation of immunity. CONCLUSIONS: A
      combination of glucan with Se offers superior stimulation of immunity and
      inhibition of cancer growth.

PMID- 27042607
TI  - A Randomized Double-Blind Placebo-Controlled Study to Compare Preemptive
      Analgesic Efficacy of Novel Antiepileptic Agent Lamotrigine in Patients
      Undergoing Major Surgeries.
AB  - BACKGROUND: If postoperative acute pain remains unrelieved, it may result in
      significant morbidity and mortality. Preemptive analgesic initiated before
      surgery offers premature analgesia even before exposure to an initial noxious
      stimulus bestowing effective postoperative analgesia. In developed countries, it
      is regularly practiced as a part of well-defined protocol. In our country
      however, only a few centers practice it and that too irregularly and with
      undefined protocol. Few studies support preemptive analgesic efficacy of novel
      antiepileptic agent gabapentin. Though lamotrigine is a proven analgesic in
      animal models of chronic pain and clinical studies of gabapentin-resistant
      neuropathic pain, a literature search revealed scarce data on its preemptive
      analgesic efficacy. AIMS: The present study is designed to study the preemptive
      analgesic efficacy of lamotrigine in comparison with diclofenac sodium in
      postoperative pain control. MATERIALS AND METHODS: This randomized clinical trial
      included 90 patients of both sexes, between 18 years and 70 years undergoing
      major surgeries. Patients were randomly allocated into placebo, control, and test
      groups and received the respective treatment 30 min before the induction of
      anesthesia. Aldrete score and pain score were recorded using visual analog scale
      (VAS), facial rating scale (FRS), and behavioral rating scale (BRS) at awakening
      and at 1 h, 2 h, 4 h, 6 h, and 24 h. Postoperative rescue analgesic consumption
      for 24 h was recorded. RESULTS: Significantly higher pain scores were observed in
      the placebo group postoperatively for 2 h on all pain scales (P < 0.05), whereas
      in the control group it was significantly higher at 1 h (P < 0.05). The test
      group patients were more comfortable throughout the study and postoperative
      analgesic requirement was significantly less (P < 0.05). CONCLUSIONS: The study
      recommends the use of single oral dose lamotrigine as preemptive analgesic for
      effective postoperative pain control.

PMID- 27042608
TI  - Can Radiology Play a Role in Early Diagnosis of Dengue Fever?
AB  - BACKGROUND: Dengue fever (DF) is a viral hemorrhagic fever causing severe
      morbidity and mortality in affected patients. AIMS: The purpose of our study was
      to evaluate the changing trends in radiological findings in DF, to find if
      ultrasound is useful in the diagnosis of DF during an epidemic in absence of
      serological tests, and also to investigate the effects of DF in pregnancy.
      MATERIALS AND METHODS: A prospective study was conducted in 2013 comprising of
      400 patients who were serologically positive for dengue. Out of these,
      radiological investigations were conducted for 107 patients who were analyzed.
      RESULTS: Out of the 107 patients, 85 patients underwent ultrasound, 12 computed
      tomography (CT) scans of brain or paranasal sinuses, and 21 chest radiography.
      The maximum numbers of patients (79%) were in the age group of 20-50 years. The
      most common ultrasound finding was hepatomegaly that was seen in 62% of the
      patients. Other findings were splenomegaly (45%), gallbladder (GB) wall edema
      (45%), right-sided pleural effusion (37%), bilateral pleural effusion (22%), and
      ascites (36%). Out of 10 pregnant patients, 5 had oligohydramnios, 2 had
      intrauterine growth restriction, 2 had intrauterine fetal demise, and 5 had a
      normal antenatal ultrasound. CONCLUSION: Ultrasound findings of
      hepatosplenomegaly, GB wall edema, right-sided or bilateral pleural effusion, and
      ascites in patients presenting with signs and symptoms of DF during an epidemic
      are virtually diagnostic of DF. There have been recent changing trends with
      hepatosplenomegaly being the more common manifestation, in comparison to ascites
      and GB wall edema. DF also has catastrophic effects in pregnancy such as
      oligohydramnios and intrauterine fetal demise.

PMID- 27042609
TI  - Evaluation Series on Safety and Efficacy of Nutritional Supplements in Newly
      Diagnosed Hyperglycemia: A Placebo-Controlled, Randomized Study.
AB  - BACKGROUND: Diabetes is endemic with developing economies contributing to the
      bulk of this pandemic. Despite the evidence of incremental benefit of glycemic
      control starting early in life, acceptance of and adherence to modern medications
      remain suboptimal. AIMS: To determine the hemoglobin A1c (HbA1c)-lowering
      efficacy and safety of nutritional supplement, PreCrea((r)), in adult Indians
      with newly diagnosed hyperglycemia. MATERIALS AND METHODS: Double-blind,
      randomized study conducted in six diabetes centers in India. A total of 193
      treatment-naive subjects with newly diagnosed hyperglycemia and fasting plasma
      glucose (FPG) >100 mg/dL were randomized into either PreCrea((r)) 600 mg (n = 90)
      or matched placebo (n = 89) capsules twice daily, along with lifestyle
      modification, for 12 weeks. The main outcomes were changes in HbA1c and FPG
      levels, attainment of the American Diabetes Association (ADA)-defined goals for
      HbA1c, and clinical and biochemical measures of safety. RESULTS: At 12 weeks,
      mean HbA1c in PreCrea((r)) group reduced by 0.91% compared with 0.08% increase in
      the placebo group (P < .001). The reductions in the mean FPG at week 4 (P < .001)
      and week 12 (P = 0.04) were significant compared to the baseline. ADA goal of
      HbA1c <7% increased from 15.5% at the baseline to 35.6% at week 12 in
      PreCrea((r)) subjects. Clinical safety and biochemical safety did not change.
      Hypoglycemia and weight gain were not observed with PreCrea((r)). CONCLUSIONS:
      Nearly 1% point reduction in HbA1c at week 12 with PreCrea((r)) is comparable
      with most first-line glucose-lowering drugs. The safety and tolerability of
      PreCrea((r)) highlights its potential as a first-line therapy in newly detected
      hyperglycemia.

PMID- 27042610
TI  - A Rare Case of Single Coronary Artery with Atherosclerotic Lesions Arising from
      the Right Sinus of Valsalva.
AB  - CONTEXT: Congenital coronary anomalies, including anomalous origin, distribution,
      intercoronary communications, and coronary fistulae occur at a rate of
      approximately 1% in the general population and are the most incidental findings.
      CASE REPORT: A 49-year-old male patient presented to the emergency department
      with exercise-induced dyspnea and atypical angina pectoris. Coronary angiography
      (CAG) and contrast-enhanced 320-slice multidetector cardiac computed tomography
      with subsequent three-dimensional reconstructions revealed a single coronary
      artery (SCA) arising from the right sinus of Valsalva with a proximal branch
      giving rise to the left anterior descending coronary artery. The left anterior
      descending coronary artery shows severe atherosclerotic lesions and it is
      occluded afterwards. Adenosine stress perfusion cardiac magnetic resonance
      imaging (MRI) revealed a stress myocardial ischemia at the anterior wall without
      signs of fibrosis, scar, or necrosis. CONCLUSION: We present an extremely rare
      case of a SCA, with the solitary vessel arising from the right sinus of Valsalva.
      In our patient's case, the atherosclerotic lesions and occlusion in the branch
      supplying the anterior wall were considered eligible for neither percutaneous
      intervention nor bypass graft surgery.

PMID- 27042611
TI  - Drug-Induced Pancreatitis: A Rare Manifestation of Doxycycline Administration.
AB  - CONTEXT: Drug-induced pancreatitis (DIP) is rare, but as there are no systematic
      data on it, the true incidence is not known. Although numerous and varied drugs
      have been associated with DIP, the clinical evidence on doxycycline-induced
      pancreatitis is sparse. CASE REPORT: We present the case of a 58-year-old female
      who presented with complaints of nausea and severe epigastric pain. Her
      medications included doxycycline which she had been on for only 2 days. Computed
      tomography of her abdomen showed mild enlargement of body of the pancreas with
      peripancreatic fatty infiltration, along with lipase level suggestive of acute
      pancreatitis. In the absence of classical risk factors for acute pancreatitis, a
      diagnosis of DIP secondary to doxycycline therapy was made. Immediate withdrawal
      of the drug was accompanied by relief of symptoms and resolution of pancreatitis.
      CONCLUSION: This report implicates doxycycline as an etiological factor for acute
      pancreatitis. Knowledge regarding doxycycline related pancreatitis is of
      paramount importance in order to diagnose cases early and institute effective
      treatment in patients who are undergoing therapy with this drug.

PMID- 27042612
TI  - Right Bundle Branch Block: A Masquerader in Acute Coronary Syndrome.

PMID- 27042613
TI  - Of orthopedists and pilots.

PMID- 27042614
TI  - NEW BEARING SURFACES IN TOTAL HIP REPLACEMENT.
AB  - Total hip arthroplasty is being increasingly indicated for younger and more
      active patients, in addition to a naturally growing demand for the procedure
      because of increasing life expectancy among patients. The high costs of this
      surgery and the controversies regarding implant performance have made this topic
      the subject of constant research, seeking new materials with better resistance to
      wear and better biocompatibility. The present article provides a review of new
      surfaces in total hip arthroplasty. 

PMID- 27042615
TI  - VISCOSUPPLEMENTATION.
AB  - With the aging of the world's population, the prevalence of age-related diseases
      is continually increasing, especially osteoarthritis, the most common form of
      joint disease. In addition to its high prevalence, osteoarthritis has been
      correlated with high medical and social costs. Among the treatment methods,
      viscosupplementation (intra-articular injection of hyaluronic acid derivatives)
      has been gaining more prominence. The substances used are high molecular weight
      polysaccharides that, in addition to mechanical functions of weight distribution
      and joint lubrication, have anti-inflammatory properties and physical-chemical
      action on a variety of joint characteristics. These effects are directly
      proportional to the molecular weight and concentration of the drug used and any
      cross-links that may be present in the drug. Viscosupplementation is a simple
      procedure and can be performed in outpatient clinics. It provides benefits
      regarding pain and function, and also favorably alters the course of the disease,
      through quantitatively and qualitatively improving the joint cartilage. It has a
      good safety profile and favorable cost-effectiveness relationship, and is
      indicated both for osteoarthritis cases and after an arthroscopic procedure. 

PMID- 27042616
TI  - OSTEOSYNTHESIS OF FEMORAL NECK FRACTURES: TWO OR THREE SCREWS?
AB  - OBJECTIVES: To evaluate the efficacy of osteosynthesis on femoral neck fractures
      using two instead of three screws. METHODS: Thirty-nine fractures were
      retrospectively evaluated, divided into groups in which two screws were used in
      parallel (n = 28) or three screws (n =11) in an inverted triangle configuration
      (in accordance with the AO technique). The patients were then followed up until
      reaching the outcome of either consolidation or failure. RESULTS: In the group in
      which two screws were used, consolidation was observed in 23 of the 28 fractures
      (82%). In the group in which three screws were used, consolidation was observed
      in 6 of the 11 fractures (55%). There was no statistically significant difference
      between these percentages. CONCLUSION: There was no difference in the prognosis
      for these fractures when treated using two screws in parallel or three screws in
      an inverted triangle in accordance with the AO technique. Further studies are
      needed in order to establish a definitive conclusion.

PMID- 27042617
TI  - ANATOMICAL STUDY ON THE LATERAL SUPRAPATELLAR ACCESS ROUTE FOR LOCKED
      INTRAMEDULLARY NAILS IN TIBIAL FRACTURES.
AB  - OBJECTIVE: Intramedullary nails are the gold standard for treating tibial shaft
      fractures. Knee pain is a frequent complication after the procedure. Alternative
      routes such as the suprapatellar approach for nail insertion are seen as an
      option for avoiding late postoperative knee pain. The question is whether this
      approach might give rise to any injury to intra-articular structures of the knee.
      METHODS: This study analyzed the suprapatellar approach and the risk to adjacent
      structures by reproducing it in 10 knees of five cadavers. RESULTS: This approach
      was seen to make it easy to locate the entry point, with lesions only occurring
      in the Hoffa fat. In three of our cases, there were lesions of the chondral
      surface, which is an obstacle that is difficult to overcome. CONCLUSION: There is
      a need to develop specific material to minimize injury to intra-articular
      structures when using this route.

PMID- 27042618
TI  - OSTEOTOMY OF THE DISTAL RADIUS USING A FIXED-ANGLE VOLAR PLATE.
AB  - OBJECTIVE: Skewed consolidation of the distal radius, due to sequelae of
      fractures, may cause functional incapacity, thus leading such patients to present
      pain, loss of strength and diminished mobility. Based on the excellent results
      obtained from surgical treatment of unstable fractures of the distal radius
      through a volar approach and use of rigid fixation with a fixed-angle volar
      plate, we started to use the same method for osteotomy of the distal radius.
      METHODS: A retrospective review was conducted, and 20 patients treated between
      February 2002 and October 2009 were found. The mean length of follow-up was 43.9
      months (range: 12 to 96 months). The surgical indications were persistent pain,
      deformity and functional limitation subsequent to a dorsally displaced fracture.
      RESULTS: The mean preoperative deformity was 27 degrees  of dorsal tilt of the
      distal radius, 87 degrees  of ulnar tilt, and 7.3 mm of shortening of the radius.
      All the osteotomies consolidated and the final mean volar tilt was 6.2 degrees ,
      with ulnar tilt of 69.3 degrees  and shortening of 1 mm. The mean mobility of the
      wrist increased by 19.9 degrees  (flexion) and by 24 degrees  (extension). Mean
      forearm supination increased by 23.5 degrees  and pronation by 21.7 degrees .
      Grip strength increased from 13.4 to 34.5 pounds. CONCLUSION: Use of a fixed
      angle volar plate for a volar approach towards osteotomy of the distal radius
      enables satisfactory correction of the deformities and eliminates the need for
      removal of the synthesis material caused by tendon complications.

PMID- 27042619
TI  - EPIDEMIOLOGICAL STUDY OF CHILDREN DIAPHYSEAL FEMORAL FRACTURES.
AB  - OBJECTIVE: To evaluate the personal, fracture, treatment and complication
      characteristics among patients with pediatric femoral shaft fractures attended at
      the pediatric orthopedic service of the Joana de Gusmao Children's Hospital.
      METHODS: This was a retrospective cross-sectional study on a population
      consisting of patients with femoral shaft fractures, aged between birth and 14
      years and 11 months, who were divided into four age groups. Information was
      obtained from medical records and was transferred to a survey questionnaire to
      present personal, fracture, treatment and complication variables. RESULTS: The
      study population consisted of 96 patients. Their mean age was 6.8 years. The
      cases were predominantly among males, comprising closed fractures on the right
      side, in the middle third with a single line. Regarding fracture etiology,
      traffic accidents predominated overall in the sample. Most of the patients (74 to
      77.1%) presented femoral fractures as their only injury. Conservative treatment
      predominated in the group younger than six years of age, and surgical treatment
      in the group aged 6 to 14 years and 11 months. The complications observed until
      bone union were: discrepancy, infection and movement limitation. The mean time
      taken for consolidation was 9.6 +/- 2.4 weeks, varying with age. CONCLUSION: The
      features of these fractures were similar to those described in the literature and
      the treatment used showed good results. The Joana de Gusmao Children's Hospital
      has used the treatment proposed in the literature for pediatric femoral shaft
      fractures.

PMID- 27042620
TI  - ANTERIOR CRUCIATE LIGAMENT INJURY: TREATMENT AND REHABILITATION. CURRENT
      PERSPECTIVES AND TRENDS.
AB  - OBJECTIVE: The aim of this study was to evaluate the procedures used by knee
      surgeons in Brazil for treating and rehabilitating anterior cruciate ligament
      injuries. METHODS: A questionnaire consisting of 21 closed questions was
      developed, addressing topics relating to treatment and rehabilitation after
      anterior cruciate ligament reconstruction. The questionnaire was applied to
      Brazilian knee surgeons during the three days of the 42(nd) Brazilian Congress of
      Orthopedics and Traumatology in 2010. RESULTS: A total of 226 surgeons filled out
      the questionnaire completely. The most commonly used types of graft were
      hamstrings tendons and the central third of the ipsilateral patellar tendon,
      which were used by 82.3% and 53.5% of the sample, respectively. The technique of
      reconstruction with a single transtibial band was the first preference and was
      used by 66.4% of the participants. A period of 1 to 4 weeks between injury and
      surgical procedure was considered ideal by most participants (52.65%). Complaints
      from patients that the knee was 'giving way' or unstable and presence of a
      positive pivot shift maneuver were the most decisive factors considered in making
      the decision to operate the patient. Patient satisfaction and absence of
      complaints of instability during the postoperative period were the criteria
      deemed to be most important for the surgery to be considered a success.
      CONCLUSIONS: There are clearly evolving trends in treating and rehabilitating the
      anterior cruciate ligament in Brazil. However, more prospective controlled
      studies are needed in order to evaluate the clinical and scientific benefits of
      these trends.

PMID- 27042621
TI  - ANATOMICAL RECONSTRUCTION OF ANTERIOR CRUCIATE LIGAMENT OF THE KNEE: DOUBLE BAND
      OR SINGLE BAND?
AB  - OBJECTIVE: To evaluate the double-band and single-band techniques for anatomical
      reconstruction of the anterior cruciate ligament of the knee and demonstrate that
      the double-band technique not only provides greater anterior stability but also
      causes less pain and a better subjective patient response. METHODS: We selected
      42 patients who underwent anterior cruciate ligament reconstruction, by means of
      either the single-band anatomical reconstruction technique, using flexor tendon
      grafts with two tunnels, or the double-band anatomical reconstruction technique,
      using four tunnels and grafts from the semitendinosus and gracilis tendons. All
      fixations were performed using interference screws. There was no variation in the
      sample. Before the operation, the objective and subjective IKDC scores, Lysholm
      score and length of time with the injury were evaluated. All these variables were
      reassessed six months later, and the KT-1000 correlation with the contralateral
      knee was also evaluated. RESULTS: There was no significant difference between the
      two groups in subjective evaluations, but the single-band group showed better
      results in relation to range of motion and objective evaluations including KT
      1000 (with statistical significance). CONCLUSION: Our study demonstrated that
      there was no difference between the two groups in subjective evaluations, but
      better results were found using the single-band anatomical technique, in relation
      to objective evaluations.

PMID- 27042622
TI  - STUDY ON THE PATELLOFEMORAL JOINT USING MAGNETIC RESONANCE IMAGING: MORPHOLOGICAL
      VARIATION OF THE MEDIAL PATELLOFEMORAL LIGAMENT.
AB  - OBJECTIVES: To study the measurements and anatomical relationships of the
      patellofemoral joint using magnetic resonance imaging, and to evaluate the
      variation in the morphology of the medial patellofemoral ligament (MPFL)
      according to patients' heights and ages and the variation in measurements on
      other structures that are known to be involved in predisposition to patellar
      instability. METHOD: Twenty-three knees (18 patients) underwent magnetic
      resonance imaging and their interepicondylar distance, patellar height, trochlear
      depth, ventral trochlear prominence, trochlear groove angle, lateral facet tilt,
      lateral patellar tilt and size of the lateral and medial facets and their ratio
      were measured. These measurements were compared with the length and thickness of
      the MPFL. RESULTS: The average length of the MPFL was 46.4 mm, while the average
      thicknesses of its patellar insertion, middle third and femoral insertion were,
      respectively, 1.7 mm, 1.4 mm and 1.2 mm. The thickness of the MPFL correlated
      positively with the lateral condyle and interepicondylar distance measurements,
      and negatively with the patients' ages. CONCLUSION: The morphology of the MPFL
      varies with the interepicondylar distance and the lateral condyle distance, and
      with patients' ages.

PMID- 27042623
TI  - ASSESSMENT OF PATELLAR HEIGHT MEASUREMENT METHODS FROM DIGITAL RADIOGRAPHY.
AB  - OBJECTIVE: To analyze the most common methods for measuring patellar height and
      the impact of observer experience in correlations with the other observers using
      digital radiography. METHODS: Sixty digital radiographs of the knee in lateral
      view were analyzed by four observers: a physician in the second year of medical
      residence in orthopedics (R2); a physician in the third year of medical residence
      in orthopedics (R3); an orthopedic surgeon who was a specialist in knee surgery
      (SK); and a radiologist who was a specialist in musculoskeletal radiology (SR).
      The indices used were: Insall-Salvati (IS), Blackburne-Peel (BP), Caton-Deschamps
      (CD) and modified Insall-Salvati (ISM). The interobserver agreement was
      calculated using the kappa coefficient (kappa). RESULTS: The highest correlation
      coefficients were found when using the IS method followed by the CD method. The
      worst correlation was observed in the ISM method. The highest interobserver
      agreement was found between the orthopedic surgeon specializing in knee surgery
      and the radiologist specializing in musculoskeletal radiology, for the four
      measurement methods used. CONCLUSION: Using digital radiography, the Insall
      Salvati and Caton-Deschamps indexes presented the highest interobserver
      agreement, and this was also positively influenced by the observer's level of
      experience.

PMID- 27042624
TI  - FUNCTIONAL ASSESSMENT OF ARTHROSCOPIC REPAIR FOR RECURRENT ANTERIOR SHOULDER
      INSTABILITY.
AB  - OBJECTIVE: To clinically and radiologically evaluate patients who underwent
      arthroscopic surgical treatment for anterior shoulder instability by means of the
      Bankart technique, using metal anchors. METHODS: This was a retrospective study
      on 49 patients who underwent arthroscopic repair of anterior shoulder instability
      between 2002 and 2007. The patients were evaluated using the Carter-Rowe score
      and the Samilson and Prieto classification. The mean age at the time of surgery
      was 30 years. The mean length of follow-up was 42.7 months (ranging from 18 to
      74). 85% of the patients were male. RESULTS: The mean Carter-Rowe score was 83
      points (ranging from 30 to 100) including 31 excellent results, 7 good, 3 fair
      and 8 poor. Recurrent dislocation was observed in 16% (8 patients), and 37.5% of
      them were of traumatic origin. Joint degeneration was present in 32.5% of the
      cases, including 5 cases of grade 1, 6 cases of grade 2 and 2 cases of grade 3.
      The average loss of external rotation was 12 degrees  and the loss of anterior
      elevation was 8 degrees . There was a statistically significant relationship (p <
      0.05) between arthritis and age at first dislocation, age at surgery and
      crackling. 92% of the patients reported high degrees of satisfaction after the
      procedure. Among the complications, there were two cases of stiff shoulder, one
      patient with prominence of the synthesis material and one case of anchor
      loosening. CONCLUSION: Arthroscopic repair of anterior shoulder instability using
      metal anchors was shown to be effective, with a low complication rate.

PMID- 27042625
TI  - ASSESSMENT OF THE RESULTS FROM ARTHROSCOPIC SURGICAL TREATMENT FOR TRAUMATIC
      ANTERIOR SHOULDER DISLOCATION: FIRST EPISODE.
AB  - OBJECTIVE: To assess the clinical results obtained of patients who underwent
      arthroscopic surgical treatment following a first episode of traumatic anterior
      shoulder dislocation. METHODS: Between August 2000 and October 2008, 14 shoulders
      of 14 patients were treated by the Shoulder and Elbow Group of Santa Casa
      Hospital, Sao Paulo. Thirteen patients (93%) were male and one (7%) was female;
      their ages ranged from 17 to 41 years, with a mean of 28 years. All of the
      patients evaluated were regularly practicing a sports activity (which required
      physical vigor of the upper limbs). The time that had elapsed between the trauma
      and the surgical treatment ranged from seven to 60 days, with a mean of 20 days.
      The surgical procedure was performed with arthroscopic viewing, with the patient
      positioned in lateral decubitus. Fixation of the labral-ligamentous complex was
      achieved using bioabsorbable anchors. The postoperative clinical assessment was
      made using Rowe and UCLA criteria. Joint mobility was measured according to the
      guidance from ASES (American Shoulder and Elbow Surgeons). The length of
      postoperative follow-up ranged from 24 to 120 months, with a mean of 45 months.
      RESULTS: All the patients achieved satisfactory results, (85% excellent and 15%
      good), as shown by UCLA, while 100% of the results were excellent according Rowe.
      The "grip test" was negative for all the patients. CONCLUSION: Surgical treatment
      after a first episode of traumatic anterior shoulder dislocation seems to be a
      good therapeutic option for young active patients who practice sports activities.

PMID- 27042626
TI  - REASSESSMENT OF PAINFUL SHOULDERS AMONG BASEBALL PLAYERS AFTER CONSERVATIVE
      TREATMENT.
AB  - OBJECTIVE: The objective of this study was to evaluate the rehabilitation results
      among baseball players who presented pain and medial rotation deficit in their
      shoulders. METHODS: Out of 55 baseball players assessed between April and June
      2009, it was observed that 20 presented pain at some instant during throwing
      movements. They were advised to undergo a rehabilitation program with exercises
      to stretch the posterior capsule and reinforce the muscles of the scapular belt,
      especially the lateral rotators. Eighteen patients followed the advice, while two
      were lost from the follow-up. The parameters evaluated were: pain, range of
      motion, strength before the program and strength after the end of the program.
      RESULTS: Comparing the initial and final assessments, we observed mean increases
      as follows: 10 degrees  of elevation (p = 0.001); three vertebral levels of
      medial rotation (p < 0.001); 20 degrees  of medial rotation at 90 degrees 
      abduction (p < 0.001); and 26 degrees  of range of motion (p < 0.001). Regarding
      strength, elevation force increased by 3 kgf (p = 0.002) and lateral rotation
      force increased by 1 kgf (p = 0.020). Out of the 18 baseball players studied, the
      pain level improved in 16, while two continued to present pain and underwent
      magnetic resonance imaging, which showed lesions for surgical treatment.
      CONCLUSION: The rehabilitation program conducted among the baseball players was
      effective and enabled increases in medial rotation, elevation, range of motion
      and strength of elevation and lateral rotation, consequently producing pain
      improvements in most of the players.

PMID- 27042627
TI  - EFFECT OF LOW-LEVEL LASER (GAAS, 904HM) FOR BONE REPAIR ON FRACTURES IN RATS.
AB  - OBJECTIVE: To analyze the effects of low-level laser therapy (GaAs, 904 nm) for
      bone repair on tibial fractures in rats. METHODS: Forty rats were divided into
      four groups of 10 animals: control group without fracture (CG); fracture group
      without treatment (EG II); fracture group treated with laser at 10 J/cm(2) (EG
      III); and fracture group treated with laser at 15 J/cm2 (EG IV). The fracture was
      produced surgically and the treatment lasted 45 days, done on alternate days.
      After treatment completion, the rats were sacrificed. The tibias were
      radiographed and subjected to mechanical three-point flexion tests in order to
      evaluate the maximum force (N) required to break them. RESULTS: The observed
      maximum force values (N) were: control group (CG) of 51.5 N +/- 7.9 N; EG II 17.2
      N +/- 7.8 N; EG III 16.6 N +/- 12.1 N; and EG IV 30.3 N +/- 7.8 N. There were
      statistically significant differences between the control group and the
      experimental groups and also between experimental group IV and the other
      experimental groups (II and III). Radiographs showed callus formation in all the
      fractured groups, thus indicating that they had undergone the normal tissue
      repair process. CONCLUSION: EG IV, which underwent laser therapy with a dosage of
      15 J/cm(2), showed the highest maximum force value (N) among the experimental
      groups, thus demonstrating the influence of higher laser dosage on bone repair.

PMID- 27042628
TI  - THE BONE SCINTIGRAPHY AS A COMPLEMENTARY EXAM IN THE DIAGNOSIS OF THE AVASCULAR
      NECROSIS OF THE SESAMOID.
AB  - OBJECTIVE: This study aimed to present seven cases of avascular necrosis of the
      sesamoid and report the role of bone scintigraphy in the diagnosis of these
      patients. METHODS: Seven patients with clinical suspicion of avascular necrosis
      of the sesamoid underwent three-phase bone scintigraphy with 30 mCi of (99m)Tc
      MDP. RESULTS: Most of the patients were young female adults with complaints of
      limiting pain in the forefoot, who were making use of inappropriate footwear
      and/or had a history of injury with or without fracture. There was no
      predominance of either of the feet or between the femoral or tibial sesamoid. Two
      patients (28.57%) had a bipartite tibial sesamoid and one (14.29%) had splitting
      of the tibial and fibular sesamoids. In 100% of the patients, three-phase bone
      scintigraphy, combined with other propaedeutic methods, proved to be crucial for
      the diagnosis. The initial procedure in all cases was conservative. In four cases
      (57.14%), there was no remission of symptoms, and surgical excision of the
      necrotized sesamoid tissue was performed. In all the patients, the therapy used
      was effective, with complete remission of symptoms, without complications or
      deformities of the forefoot. CONCLUSIONS: Three-phase bone scintigraphy becomes a
      cornerstone of the propaedeutics when avascular necrosis of the sesamoid is
      suspected, through contributing towards early and accurate diagnosis and enabling
      allowing appropriate specialized treatment.

PMID- 27042629
TI  - FEMORAL TUNNELS' LENGTH CHANGES WITH KNEE FLEXION ANGLE IN ANATOMICAL ANTERIOR
      CRUCIATE LIGAMENT RECONSTRUCTION.
AB  - OBJECTIVE: The objective of our study was to evaluate the effect that knee
      flexion angle while femoral tunnels are being drilled may have on the length of
      these tunnels, in anatomical reconstruction of the anterior cruciate ligament.
      METHODS: We measured the lengths of anteromedial and posterolateral tunnels for
      the anterior cruciate ligament in 20 unpaired anatomical knee specimens (10 right
      and 10 left knees), all with the cartilage and cruciate ligaments intact. Tunnels
      were drilled with the knees flexed at 90 degrees , 110 degrees  and 130 degrees ,
      through the accessory anteromedial portal, with a 2.5 mm drill. The statistical
      analysis was done by means of Friedman's variance analysis and the Mann-Whitney U
      test. RESULTS: The mean anteromedial femoral tunnel lengths measured with the
      knees flexed at 90 degrees , 110 degrees  and 130 degrees  were 33.7 (+/- 3.72)
      mm, 37.4 (+/- 2.93) mm and 38.8 (+/- 3.31) mm, respectively. For the
      posterolateral femoral tunnel lengths, the results were 32.1 (+/- 4.24) mm, 37.3
      (+/- 4.85) mm and 38.4 (+/- 2.51) mm, respectively. Friedman's variance analysis
      showed that there was a significant difference between the lengths of the tunnels
      drilled with 90 degrees  and 110 degrees  of flexion angle, but showed that there
      was no significant difference between the tunnels drilled with flexion of 110
      degrees  and 130 degrees  (P < 0.05). CONCLUSIONS: It is possible to drill the
      femoral tunnels through the accessory anteromedial tunnel with the knee flexed at
      110 degrees  in such a way as to produce a tunnel of sufficient length for a good
      bone-graft interface.

PMID- 27042630
TI  - SEVERE VALGUS DEFORMITY OF THE KNEE: DESCRIPTION OF NEW SURGICAL TECHNIQUE FOR
      ITS CORRECTION.
AB  - Varus supracondylar osteotomy of the femur is the established procedure for
      treating painful knees that present lateral arthrosis and valgus deformity. In
      descriptions of the conventional surgical techniques, there are divergences
      regarding the location, access route, correction level, fixation type and area
      for synthesis insertion. This is most evident in cases of severe valgus with
      angles greater than 30 degrees  and distal femoral deformation, in association
      with hypoplasia of the lateral condyle. The authors describe a new surgical
      technique for distal femoral osteotomy, based on anatomical and geometrical
      criteria, which was developed in their clinic for treating severe valgus cases,
      and they present one of the cases treated. In the new technique, the wedge to be
      surgically resected has an oblique direction and the format of an isosceles
      triangle. This new proposal thus seeks to resolve problems that have been
      presented in such cases, through enabling valgus correction without causing any
      new deformity of the distal femur. Good cortical bone contact is promoted, and
      application of a stable synthesis system is made easier. However, the age limits
      for such patients and the degree of knee arthrosis that might contraindicate this
      procedure remain unknown. Hence, a larger sample and longer follow-up for
      operated cases are required. 

PMID- 27042631
TI  - BILATERAL OSTEOCHONDRITIS DISSECANS OF THE KNEE IN A BASKETBALL PLAYER: CASE
      REPORT.
AB  - The authors report a case of bilateral osteochondritis dissecans in a 17-year-old
      basketball player who was diagnosed and treated as shown in the literature. 

PMID- 27042632
TI  - OSTEOID OSTEOMA IN THE ILIAC BONE: REPORT ON TWO CASES.
AB  - Osteoid osteoma is a benign bone tumor that generally presents with nighttime
      pain among young adults and is relieved by rest and salicylates. It can affect
      any bone, but occurrences in the iliac are unusual. The authors describe two
      cases of intramedullary osteoid osteoma next to the sacroiliac joint, with
      symptoms that simulated sciatic pain. The cases were diagnosed late, although the
      initial radiographs showed sclerotic lesions in both cases. The diagnosis was
      confirmed by means of CT scan and the nidus was excised surgically through en
      bloc resection. The definitive diagnosis was given by means of histopathological
      examination. Over long-term follow-up, both cases remained asymptomatic and
      complete bone remodeling at the surgical site was observed. The authors highlight
      the typical characteristics of the tumor, the unusual location, the differential
      diagnosis and the treatment. 

PMID- 27042634
TI  - Latin American Journal of Orthopedics and Traumatology.

PMID- 27042633
TI  - PARAGANGLIOMA IN THE SPINE: CASE REPORT.
AB  - Paragangliomas are rare neuroendocrine tumors that originate in specialized cells
      derived from neural crest cells, affecting the region of the carotid or jugular
      tympanic artery. They are rare within the spinal canal and, when they occur, they
      are normally found in the extramedullary intradural compartment of the
      lumbosacral region. This report presents the case of a 26-year-old male patient
      who was diagnosed with pathological fracture of the thoracic spine (T10),
      secondary to paraganglioma, thus causing complete spinal cord injury. Surgical
      treatment was performed at the General Hospital of the State of Bahia and the
      complication of excessive bleeding occurred, which indicated that there had been
      a need for prior embolization. Because of this, the authors recommend caution
      when evaluating and treating this rare lesion that causes neurological deficits,
      with careful surgical planning in order to catastrophic complications. 

PMID- 27042635
TI  - DEGENERATIVE STENOSIS OF THE LUMBAR SPINE.
AB  - This paper presents an update on degenerative stenosis of the lumbar spine, which
      is a common pathological condition among patients over the age of 65 years. The
      anamnesis and physical examination need to be precise, since radiography often
      only provides indirect signs. Magnetic resonance imaging is necessary if the
      symptoms persist. The treatment for lumbar stenosis is a matter of controversy.
      However, there seems to be some benefit from surgical treatment rather than
      conservative treatment, such that surgery brings improvements in symptoms and
      functions for a period of up to two years. 

PMID- 27042636
TI  - PSEUDARTHROSIS OF THE SCAPHOID IN IMMATURE SKELETONS.
AB  - This paper presents a review of the literature on pseudarthrosis of the scaphoid
      in skeletally immature individuals, taking into consideration its epidemiology,
      diagnosis and treatment, as well as its controversies. Knowledge of this subject
      makes it possible for patients to be given appropriate treatment immediately.
      Pseudarthrosis of the scaphoid in skeletally immature patients is a rare
      condition that results from error or lack of diagnosis of a fracture. Thus,
      careful clinical and radiographic examination should be performed in order to
      confirm or rule out this diagnosis. Several treatment methods have been reported
      and have shown good results. These include conservative plaster cast treatment,
      bone graft without osteosynthesis, bone graft with Kirschner wires, percutaneous
      screws and bone graft with compression screws. The treatment performed depends on
      the characteristics of the pseudarthrosis and the surgeon's experience. 

PMID- 27042637
TI  - STATISTICAL ANALYSIS ON FUNCTIONAL AND RADIOGRAPHIC RESULTS AFTER USE OF LOCKED
      VOLAR PLATE FOR FRACTURES OF THE DISTAL RADIUS.
AB  - OBJECTIVES: To evaluate the functional results from using a fixed-angle locked
      volar plate for treating fractures of the distal extremity of the radius, using
      the DASH (disorders of the arm, shoulder and hand) questionnaire and its
      radiographic correlation with the Lidstrom classification. METHODS: Thirty
      patients with unstable fractures of the distal extremity of the radius were
      evaluated after they had undergone a surgical procedure consisting of open
      reduction and internal fixation using a fixed-angle locked volar plate, at the
      Military Police Central Hospital of Rio de Janeiro between 2008 and 2009. The
      results were assessed based on range of motion, DASH protocol scores and
      radiographies with the Lidstrom classification. RESULTS: The mean age of the
      patients in the study was 51 years. The mean DASH score was 11.9 points. It was
      observed that the radiographic findings did not influence the DASH score. It was
      found that flexion, pronation, supination and radial deviation correlated with
      the DASH score. CONCLUSIONS: The study showed that subjective functional outcomes
      using the DASH protocol, obtained from using a locked volar plate to treat
      fractures of the distal extremity of the radius, are influenced by the range of
      motion, and especially by the flexion, supination, pronation and radial deviation
      of the wrist after surgery. There is no correlation between the radiological
      parameters of either the normal or the operated radius, and the subjective
      functional outcomes assessed using the DASH protocol.

PMID- 27042638
TI  - EVALUATION OF THE MORTALITY RATE ONE YEAR AFTER HIP FRACTURE AND FACTORS RELATING
      TO DIMINISHED SURVIVAL AMONG ELDERLY PEOPLE.
AB  - OBJECTIVE: To evaluate the mortality rate after one year and correlated
      preoperative factors, among patients with hip fractures. METHODS: We
      prospectively studied 202 out of a total of 376 patients with a diagnosis of hip
      fracture who were admitted to the Hospital Cristo Redentor, between October 2007
      and March 2009. The database with the epidemiological analysis was set up during
      their hospitalization, and follow-up data were obtained preferentially by phone.
      RESULTS: The overall mortality rate after one year of follow-up was 28.7% or 58
      deaths, among which 11 (5.45%) occurred during hospitalization. Fractures were
      more prevalent among women (71.3%) and rare among blacks (5%). Among the
      comorbidities, dementia and depression showed a statistically significant
      reduction in survival (p = 0.018 and 0.007, respectively). CONCLUSION: The
      mortality rate after one year of follow-up was 28.7%. Dementia and depression
      increased this rate.

PMID- 27042639
TI  - EVALUATION OF PATIENTS UNDERGOING FIXATION OF DIAPHYSEAL HUMERAL FRACTURES USING
      THE MINIMALLY INVASIVE BRIDGE-PLATE TECHNIQUE.
AB  - OBJECTIVE: The aim was to describe the experience of our group in treating
      humeral shaft fractures using the bridge-plate technique via an anterior
      approach. METHODS: Seventeen patients with acute diaphyseal humeral fractures
      with an indication for surgical treatment who were operated in 2006-2010 were
      evaluated. The AO and Gustilo & Anderson classifications were used. All the
      patients were operated using the anterior bridge-plate technique and completed a
      follow-up period of at least twelve months. RESULTS: Sixteen men and one woman
      were treated. Their mean age was 31.8 years (18-52). Among the injury mechanisms
      found were: five motorcycle accidents, four car accidents, three fractures due to
      firearm projectiles, two falls to the ground and finally, with one case each,
      assault, crushing and being run over. Eight patients had open fractures: two
      grade I, one grade II, four grade IIIa and one grade IIIb, according to the
      Gustilo-Anderson classification. In relation to the AO classification, we found:
      one 12A1, three 12A2, four 12A3, one 12B1, four 12 B2, three 12B3 and one 12C2.
      The mean postoperative follow-up was 25 months (12-48). As complications, two
      patients had pain in the elbow and a ROM deficit and one had deep infection. The
      mean time taken to achieve consolidation was 17.5 weeks. There was no loss of
      reduction, pseudarthrosis or malunion in this series of patients. CONCLUSION: The
      authors believe that the technique described has low rates of complications and
      morbidity, with good initial results, although the series is limited by the small
      sample.

PMID- 27042640
TI  - EVALUATION OF THE RESULTS FROM ARTHROSCOPIC SURGICAL TREATMENT FOR TRAUMATIC
      ANTERIOR SHOULDER INSTABILITY USING SUTURING OF THE LESION AT THE OPENED MARGIN
      OF THE GLENOID CAVITY.
AB  - OBJECTIVE: To evaluate the clinical results from patients with traumatic anterior
      shoulder instability that was treated surgically through arthroscopic viewing,
      using bioabsorbable anchors and a technique for remove the cartilage of the
      anterior glenoid rim for repairing a Bankart lesion. METHOD: Between March 2006
      and October 2008, 27 shoulders in 27 patients with a diagnosis of traumatic
      anterior shoulder instability were operated. The patients' mean age was 28 years
      and they had had between two and 25 previous episodes of dislocation. The
      patients were predominantly male (24; 89%). The minimum length of follow-up was
      24 months and the mean was 36 months. None of the patients had previously
      undergone surgery on the affected shoulder or had any significant bone lesion at
      the glenoid margin. The postoperative clinical assessment was done using the Rowe
      scale. To measure the preoperative and postoperative joint range of motion, we
      used the method described by the American Academy of Orthopaedic Surgeons (AAOS).
      RESULTS: According to the Rowe criteria, 25 patients (93%) achieved excellent
      results and two (7%) had poor results. None of the patients presented good or
      fair results. Twenty-three patients were satisfied with the results obtained
      (85%), and returned to their activities without limitations, while four patients
      (15%) had some degree of limitation. There was recurrence of instability in two
      patients (7%). CONCLUSION: Treatment of traumatic anterior shoulder instability
      through arthroscopic viewing using a technique for remove the cartilage of the
      anterior glenoid rim for repairing a Bankart lesion provided excellent results
      for 93% of the patients operated.

PMID- 27042641
TI  - ARTHROSCOPIC TREATMENT OF POST-TRAUMATIC ELBOW STIFFNESS.
AB  - To evaluate patients undergoing arthroscopic release of a stiff elbow, with
      discussion of the technique, possible difficulties and risks. METHODS: Twenty
      four elbow arthroscopy procedures were performed. All the patients were evaluated
      using goniometry before the operation and six months afterwards and were rated
      using the Mayo elbow performance score (MEPS). RESULTS: Fifteen men and nine
      women underwent surgery (14 right elbows and ten left elbows). Their mean age was
      34.58 years and length of follow-up, 38.41 months. Their mean gain of range of
      motion was 43.3 degrees  and of MEPS, 85.4. CONCLUSION: Arthroscopic release
      might enable better intra-articular viewing and enhance the options for changing
      strategy during surgery, reducing surgical trauma and enabling early
      rehabilitation. This technique can reach similar or better results than open
      surgery. The disadvantages of arthroscopy are the long learning curve and higher
      cost of the procedure. Neurovascular complications are reported with both
      techniques. To avoid such problems, the protocol for portal construction must be
      rigorously followed. Arthroscopic release was shown to be a safe and effective
      option for achieving range-of-motion gains in cases of post-traumatic stiff
      elbow.

PMID- 27042642
TI  - RESULTS FROM ARTHROSCOPIC REPAIR OF ISOLATED TEARS OF THE SUBSCAPULARIS TENDON.
AB  - OBJECTIVE: To evaluate the functional and clinical outcomes and identify
      prognostic factors in patients undergoing arthroscopic repair of isolated tears
      of the subscapularis tendon. METHODS: Between January 2003 and May 2009, we
      identified 18 shoulders with isolated tears or deinsertions that were complete or
      affected at least one third of the subscapularis tendon and underwent
      arthroscopic repair. RESULTS: Three shoulders (17%) showed lesions in the upper
      third of the subscapularis; nine shoulders (50%) showed lesions in the upper two
      thirds; and six shoulders (33%) presented complete tears. In comparing the range
      of lateral rotation of the injured shoulder between before surgery and the time
      of the reevaluation, there was no statistical difference (p = 0.091). The LHBT
      was damaged in 11 shoulders (61%). According to the Constant score validation, we
      had excellent and good results in 83% of the cases and 17% were reasonable. The
      reevaluations on three patients showed re-tearing on MRI. Acromioplasty was
      performed on ten patients and this procedure did not represent statistical
      differences in the final results (p = 0.57). CONCLUSIONS: There was no
      statistically significant difference in relation to preoperative lateral rotation
      between the injured shoulder and the contralateral side. There was no significant
      loss of lateral rotation after surgery. The LHBT may be normal in deinsertions of
      the subscapularis tendon. Acromioplasty did not influence the results. The re
      tearing rate for arthroscopic repair of the subscapularis tendon was 16.6%.

PMID- 27042643
TI  - OSTEOTOMIES OF THE CORACOID PROCESS: AN ANATOMICAL STUDY.
AB  - OBJECTIVE: Relate the main tendinous and ligamentous structures attached in the
      coracoid process, correlating it to several levels of osteotomy and describing
      the involved structures. METHODS: Thirty shoulders were dissected. The coracoid
      process with mainly inserted anatomic structures was dissected, and five levels
      of osteotomy (1.0; 1.5; 2.0; 2.5; 3.0 cm) were made from the apex of the process
      and the mainly involved structures were recorded. RESULTS: In osteotomies of 1.0
      cm, in 100% of the cases only the conjoint tendon (CT). In osteotomies of 1.5 cm
      there were 63.33% of cases involved with the CT and the Pectoralis minor (PMi),
      in 20% of cases only the CT, and in 16.66% the CT, PMi, and the coracohumeral
      ligament (CUL). In osteotomies of 2.0 cm, in 80% of the shoulders, the
      osteotomies embraced the CT, PMi and the CUL, and in 20% only the CT and the PMi
      were involved. In the osteotomies of 2.5cm there was involvement of the CT, PMi
      and CUL in 100% of cases. In the osteotomies of 3.0cm, six cases (20%) have
      presented an injury on the trapezoid ligament, and in 100% of these osteotomies,
      the osteotomized distal fragment had embraced the CT, PMi, CUL. CONCLUSION: The
      knowledge of anatomic structures inserted and involved in the osteotomies cuts of
      the coracoid process is very importan to lead with osteotomies performed in the
      treatment techniques of the coracoid process. Osteotomies of 3.0 cm can injure
      the trapezoid ligament.

PMID- 27042644
TI  - PROSPECTIVE STUDY ON TACTILE SENSITIVITY IN THE HANDS OF A BRAZILIAN POPULATION
      USING THE PRESSURE-SPECIFIED SENSORY DEVICE.
AB  - OBJECTIVE: To evaluate the pressure perception thresholds on the pulp of two
      fingers (index and little fingers), among a Brazilian population with no nerve
      injury or neuropathy. METHODS: We used the Pressure-Specified Sensory Device (a
      computerized device) to derive static and dynamic normal pressure perception
      thresholds and two-point discrimination distances. RESULTS: We tested finger
      sensitivity on 30 volunteers. Significance analyses were performed using the
      Student t test. The mean values (g/mm(2)) for static one and two-point pressure
      thresholds (s1PD, s2PD) and dynamic one and two-point discrimination (m1PD, m2PD)
      in the dominant index finger were: s1PD = 0.4, m1PD = 0.4, s2PD = 0.48, m2PD =
      0.51. CONCLUSION: There was no significant difference in sensitivity between the
      dominant and nondominant hands.

PMID- 27042645
TI  - OSTEOCHONDRAL AUTOLOGOUS TRANSPLANTATION FOR TREATING CHONDRAL LESIONS IN THE
      PATELLA.
AB  - OBJECTIVE: The primary aim of this study was to assess the clinical and
      functional evolution of patients with total-thickness symptomatic cartilaginous
      injury of the patellar joint surface, treated by means of osteochondral
      autologous transplantation. METHODS: This prospective study was conducted from
      June 2008 to March 2011 and involved 17 patients. The specific questionnaires of
      Lysholm, Kujala and Fulkerson were completed preoperatively and one year
      postoperatively in order to assess the affected knee, and SF-36 was used to
      assess these patients' general quality of life. The nonparametric paired Wilcoxon
      test was used for statistical analysis on the pre and postoperative
      questionnaires. The data were analyzed using the SPSS for Windows software,
      version 16.0, and a significance level of 5% was used. RESULTS: The Lysholm
      preoperative and postoperative average scores were 54.59 and 75.76 points (p <
      0.05). The Fulkerson pre and postoperative average scores were 52.53 and 78.41
      points (p < 0.05). CONCLUSIONS: We believe that autologous osteochondral
      transplantation is a good treatment method for total-thickness symptomatic
      chondral lesions of the joint surface of the patella.

PMID- 27042646
TI  - RANDOMIZED PROSPECTIVE STUDY COMPARING TRANSVERSE AND EXTRACORTICAL FIXATION IN
      ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.
AB  - OBJECTIVE: This study had the objective of prospectively comparing transverse
      fixation (Cross-PinTM) with extracortical fixation (EZLocTM) for the femur, in
      surgical reconstruction of the anterior cruciate ligament, from a clinical,
      biomechanical and functional point of view. METHODS: Between April 2007 and
      November 2009, 50 patients with acute or chronic anterior cruciate ligament
      injuries underwent arthroscopic reconstruction using the homologous flexor
      tendons (gracilis and semitendinosus). Randomization of the femoral fixation
      method was done by means of a draw at the time of the procedure. Patients were
      excluded if they presented multiple ligament lesions, fractures, previous
      surgery, autoimmune disease and impairment of the contralateral knee. The Lysholm
      scale, SF36 quality-of-life questionnaire and KT1000TM arthrometer were used.
      RESULTS: After a mean follow-up of 18.1 months, there were no statistically
      significant differences between the groups regarding the Lysholm scale and
      KT1000TM measurements. However, the SF36 questionnaire showed a statistical
      difference such that transverse fixation was superior regarding pain and
      vitality. CONCLUSION: Both techniques were shown to be efficient for transfemoral
      fixation, but with almost no statistically significant difference between them.
      We believe that new studies will be necessary for better understanding of these
      differences.

PMID- 27042647
TI  - NAVIGATED VERSUS MECHANICAL KNEE REPLACEMENT: COMPARISON BETWEEN INITIAL
      NAVIGATED AND CONVENTIONAL CASES PERFORMED BY THE SAME SURGEON.
AB  - OBJECTIVE: The postoperative mechanical axis in 36 cases of total knee
      arthroplasty using navigated and mechanical alignment systems was evaluated and
      compared. All the operations were performed over the same period by the same
      surgeon and team, who were beginners in the navigated technique and experienced
      in the mechanical technique. METHODS: Between 2008 and 2010, 36 total knee
      prostheses were performed and compared: 25 navigated and 11 mechanical
      procedures. Any deviation from the axis measured on the panoramic postoperative X
      ray was considered positive. RESULTS: The navigated prostheses produced a mean
      axis deviation of 1.32 degrees and standard deviation of 1.57 degrees and the
      mechanical, respectively 3.18 and 2.99 degrees. There was better alignment with a
      tendency towards a statistical difference favoring the navigated technique.
      CONCLUSION: There were significantly more cases with axis deviation greater than
      three degrees using the mechanical technique. The navigated technique was
      incorporated by this team without additional complications and, even without
      experience of navigated surgery, the initial cases achieved better alignment than
      with the mechanical technique, and a significantly smaller number of outliers
      from the three-degree safety zone.

PMID- 27042648
TI  - EVALUATION OF THE INTERMETATARSAL ANGLE AFTER THE ARTHRODESIS OF THE FIRST
      METATARSOPHALANGEAL JOINT FOR TREATMENT OF THE HALLUX VALGUS.
AB  - OBJECTIVE: To evaluate the correction of the intermetatarsal angle after
      arthrodesis of the metatarsophalangeal joint of the hallux. We believe that varus
      deformity of the first metatarsal can be corrected after arthrodesis of the first
      metatarsophalangeal joint, without the need for proximal osteotomy. METHODS:
      Forty-three feet of patients who had undergone arthrodesis of the first
      metatarsophalangeal joint between May 1997 and October 2009 were retrospectively
      analyzed by means of radiographs. The mean length of follow-up was 58 months.
      Measurements on the metatarsophalangeal angle, intermetatarsal angle and sesamoid
      dislocation were made using radiographs made before, immediately after and later
      on after the operation. RESULTS: The mean metatarsophalangeal angle was 37.6
      degrees preoperatively, 12.8 degrees immediately after the operation and 16.4
      degrees later on after the operation. The mean intermetatarsal angle was 16
      degrees preoperatively, 10 degrees immediately after the operation and 10.2
      degrees later on after the operation. Regarding sesamoid dislocation,
      preoperative radiographs showed most feet to be classified as G3; immediately
      after the operation, most were classified as G2; and later on after the
      operation, most were G1. CONCLUSION: The intermetatarsal angle and sesamoid
      dislocation improved with arthrodesis of the first metatarsophalangeal joint,
      without the need for osteotomy at the base of the first metatarsal.

PMID- 27042649
TI  - ARE THERE DIFFERENCES IN STRENGTH TESTS USING ISOKINETIC DYNAMOMETRY BETWEEN
      FIELD AND INDOOR PROFESSIONAL SOCCER PLAYERS?
AB  - OBJECTIVE: The objective of this study was to conduct a comparative analysis on
      isokinetic strength assessments between field and indoor male professional soccer
      players and correlate the findings with the higher levels of injury risk
      described in the literature. METHODS: We analyzed 16 field soccer players and 15
      indoor soccer players. All these professionals were male. Isokinetic muscle
      strength assessments were made on their knees. RESULTS: The mean weight was 81.81
      kg for field soccer and 80.33 kg for indoor soccer. The right and left peak
      extensor torque left and right for field soccer and indoor soccer were,
      respectively, 302.50 and 313.31 Nm and 265.20 and 279.80 Nm, and for flexors, 178
      and 184.88 Nm and 158.27 and 154 Nm. The peak torque rates according to body
      weight for the left and right extensors for field soccer and indoor soccer were,
      respectively, 3.84 and 3.7 Nm/kg and 3.32 and 3.52 Nm/kg, and for flexors, 2.17
      and 2.26 Nm/kg and 1.98 and 1.93 Nm/kg. The balance relationships between flexors
      and extensors on the right and left sides for field soccer and indoor soccer
      were, respectively, 59.81 and 59.44% and 60.47% and 54.80%. The relationships for
      extensors between the right and left sides for field soccer and indoor soccer
      were, respectively, 11.44 and 9.20%, and for the flexors, 7.31 and 8.80%.
      CONCLUSIONS: In accordance with international parameters, comparative analysis on
      isokinetic strength assessments between field and indoor male professional soccer
      players before the season showed that there was muscle balance and low
      probability of injury. There were no statistically significant differences in the
      parameters analyzed between the players of the two types of soccer.

PMID- 27042650
TI  - VIABILITY OF VASCULARIZED BONE GRAFT FROM THE ILIAC CREST USING THE ILIAC BRANCH
      OF THE ILIOLUMBAR ARTERY: EXPERIMENTAL STUDY ON RATS.
AB  - OBJECTIVE: Through an experimental model, our aim was to create inferences about
      the viability of vascularized bone grafts from the iliac crest in rats and
      investigate their histological features. METHODS: Twenty-one rats were used,
      divided into two groups: the first consisted of animals that were subjected to
      the technique of vascularized bone graft pedicled onto the iliac branch of the
      iliolumbar artery; the second (control group) underwent the same procedure as
      performed on the first group, with the addition of ligation of the vascular
      pedicle. The viability of the bone grafts was observed for three weeks, by means
      of direct observation of the graft, histology and immunohistochemistry. RESULTS:
      All the vascularized grafts evaluated in the first week showed viability
      according to direct observation, histology and immunohistochemistry. However, in
      the second and third weeks, direct observation showed that 75% of the grafts were
      unviable, while histological analysis and immunohistochemistry showed that 50%
      were unviable. CONCLUSIONS: Some grafts that are designed to be vascularized
      became unviable and began to behave like non-vascularized grafts under direct
      observation and histology. Despite the possibility of failure, use of
      vascularized bone grafts should be encouraged, because descriptive histology
      shows greater cell density in the medullary bone portion, and osteocytes that
      function better regarding deposition of bone matrix, with preservation of the
      intraosseous vascular network.

PMID- 27042651
TI  - SIMULTANEOUS BILATERAL AVULSION FRACTURE OF THE TIBIAL TUBEROSITY IN A TEENAGER:
      CASE REPORT AND THERAPY USED.
AB  - Simultaneous bilateral avulsion fracture of the tibial tuberosity in teenagers is
      a rare lesion. We describe the first case in the literature, in a teenage girl
      who sustained a fall while jumping during a volleyball match. No predisposing
      factors were iden tified. The lesions were treated with open surgical reduction
      and internal fixation. The aim of the present study was to present a case of
      simultaneous bilateral avulsion fracture of the tibial tuberosity in a teenage
      girl and the therapy used. 

PMID- 27042652
TI  - CIRCUMFERENTIAL PROXIMAL FEMORAL ALLOGRAFTS IN REVISION SURGERY ON TOTAL HIP
      ARTHROPLASTY: CASE REPORTS WITH A MINIMUM FOLLOW-UP OF 20 YEARS.
AB  - Among the options for femoral reconstruction in total hip arthroplasty (THA)
      revision procedures, in cases of extensive circumferential defects, is the use of
      proximal femoral allografts. This technique makes it possible to correct the hip
      abductor mechanism and the leg length discrepancy, as well as presenting
      osteoconductive potential. The authors report the clinical and radiographic
      results from two cases of THA revision using this technique, with a minimum
      follow-up of 20 years. 

PMID- 27042653
TI  - SPONTANEOUS OSTEONECROSIS IN AN ATHLETE'S KNEE TREATED USING A HYPERBARIC
      CHAMBER: CASE REPORT AND REVIEW OF THE LITERATURE.
AB  - Osteonecrosis is a clinical syndrome characterized by osseous necrosis of a load
      bearing portion of the femoral condyle, followed by subchondral fracturing,
      subsequent segmental collapse and arthrosis. It most frequently affects obese
      women over the age of 55 years. Its treatment is still a matter of controversy in
      the literature. The authors report the case of a 24-year-old male patient who was
      a professional soccer player, who presented with a complaint of knee pain one day
      after physical activity. Imaging examinations performed early on already
      demonstrated the start of the lesion. The treatment, which was successful, used
      the following: withdrawal of support, physiotherapy, medications (such as NSAIDs
      and bisphosphonates) and a hyperbaric chamber. Although hyperbaric chamber
      therapy is new, its use in association with drug therapy and withdrawal of
      support may bring good results in treating idiopathic osteonecrosis, even for
      athletes with high physical demands. However, there is a need for further reports
      and studies with greater evidence, in order to demonstrate the validity of this
      treatment. 

PMID- 27042654
TI  - MYOSITIS OSSIFICANS PROGRESSIVA: CASE REPORT.
AB  - Myositis ossificans progressiva is a rare autosomal dominant disease with less
      than 1,000 case reports. Such patients present edema, caused by inflammatory
      processes that progressively calcify, and with loss of mobility in the region
      affected. The objective of this study was to describe a case of myositis
      ossificans progressiva, present its clinical manifestations and discuss the
      treatments available (oral ascorbic acid and intravenous bisphosphonate). 

PMID- 27042655
TI  - Evaluation of Stress Intensity and Anxiety Level in Preoperative Period of
      Cardiac Patients.
AB  - INTRODUCTION: The stress related to patient's stay in a hospital increases when
      it is necessary to perform a surgery. Therefore, the study of the phenomenon of
      stress intensity in hospitalized patients has become an important issue for
      public health. MATERIAL AND METHOD: The study was conducted in University
      Hospital No. 1 in the cardiosurgery clinic. The study involved 58 patients who
      were admitted as planned to the hospital. The study used a standardized
      questionnaire measuring intensity of the stress and also deepened interviews with
      patients about stress and anxiety felt before the surgery. RESULTS: The greater
      the patient's anxiety resulting from his state of health, the greater the
      intensity of stress in the preoperative period. This relationship is linear. The
      results of the study also made it possible to see intrapersonal factors (pain,
      illness, and suffering) and extrapersonal factors (anesthesia, surgery, and
      complications after surgery), which are causes of anxiety before surgery.
      CONCLUSION: The research showed high (negative) results of anxiety and stress
      associated with the disease, surgery, and complications after cardiac surgery.
      Active involvement in hospitalization elements, such as patient education before
      surgery, psychological support, and medical care organization taking into account
      patient's preferences, reduces the impact of stressors.

PMID- 27042657
TI  - Clinical Characteristics and 30-Day Outcomes of Intermittent Hemodialysis for
      Acute Kidney Injury in an African Intensive Care Unit.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a common occurrence in the intensive
      care unit (ICU). Studies have looked at outcomes of renal replacement therapy
      using intermittent haemodialysis (IHD) in ICUs with varying results. Little is
      known about the outcomes of using IHD in resource-limited settings where
      continuous renal replacement therapy (CRRT) is limited. We sought to determine
      outcomes of IHD among critically ill patients admitted to a low-income country
      ICU. METHODS: A retrospective review of patient records was conducted. Patients
      admitted to the ICU who underwent IHD for AKI were included in the study.
      Patients' demographic and clinical characteristics, cause of AKI, laboratory
      parameters, haemodialysis characteristics, and survival were interpreted and
      analyzed. Primary outcome was mortality. RESULTS: Of 62 patients, 40 had complete
      records. Median age of patients was 38.5 years. Etiologic diagnoses associated
      with AKI included sepsis, malaria, and ARDS. Mortality was 52.5%. APACHE II (OR
      4.550; 95% CI 1.2-17.5, p = 0.028), mechanical ventilation (OR 13.063; 95% CI 2.3
      72, p = 0.003), and need for vasopressors (OR 16.8; 95% CI 3.4-82.6, p = 0.001)
      had statistically significant association with mortality. CONCLUSION: IHD may be
      a feasible alternative for RRT in critically ill haemodynamically stable patients
      in low resource settings where CRRT may not be available.

PMID- 27042656
TI  - Synergistic Effect and Molecular Mechanisms of Traditional Chinese Medicine on
      Regulating Tumor Microenvironment and Cancer Cells.
AB  - The interaction of tumor cells with the microenvironment is like a relationship
      between the "seeds" and "soil," which is a hotspot in recent cancer research.
      Targeting at tumor microenvironment as well as tumor cells has become a new
      strategy for cancer treatment. Conventional cancer treatments mostly focused on
      single targets or single mechanism (the seeds or part of the soil); few
      researches intervened in the whole tumor microenvironment and achieved ideal
      therapeutic effect as expected. Traditional Chinese medicine displays a broad
      range of biological effects, and increasing evidence has shown that it may relate
      with synergistic effect on regulating tumor microenvironment and cancer cells.
      Based on literature review and our previous studies, we summarize the synergistic
      effect and the molecular mechanisms of traditional Chinese medicine on regulating
      tumor microenvironment and cancer cells. 

PMID- 27042658
TI  - Computer-Assisted Classification Patterns in Autoimmune Diagnostics: The AIDA
      Project.
AB  - Antinuclear antibodies (ANAs) are significant biomarkers in the diagnosis of
      autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF)
      method, and performed by analyzing patterns and fluorescence intensity. This
      paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer)
      developed in the framework of an Italy-Tunisia cross-border cooperation and its
      preliminary results. A database of interpreted IIF images is being collected
      through the exchange of images and double reporting and a Gold Standard database,
      containing around 1000 double reported images, has been settled. The Gold
      Standard database is used for optimization of a CAD (Computer Aided Detection)
      solution and for the assessment of its added value, in order to be applied along
      with an Immunologist as a second Reader in detection of autoantibodies. This CAD
      system is able to identify on IIF images the fluorescence intensity and the
      fluorescence pattern. Preliminary results show that CAD, used as second Reader,
      appeared to perform better than Junior Immunologists and hence may significantly
      improve their efficacy; compared with two Junior Immunologists, the CAD system
      showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%), higher Patterns
      Accuracy (79,3% versus 48,0% and 66,2%), and higher Mean Class Accuracy (79,4%
      versus 56,7% and 64.2%). 

PMID- 27042659
TI  - Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer
      Formulations.
AB  - Formulating appropriate storage conditions for biopharmaceutical proteins is
      essential for ensuring their stability and thereby their purity, potency, and
      safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor
      system, multiple formulation compositions were systematically explored in a DoE
      design to optimize the stability of a challenging antibody formulation worst
      case. The stability of the antibody in each buffer formulation was assessed by
      UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid
      chromatography (SEC) to determine overall solubility, opalescence, and aggregate
      formation, respectively. Upon preliminary testing, acetate was eliminated as a
      potential storage buffer due to significant visible precipitate formation. An
      additional 2(4) full factorial DoE was performed that combined the stabilizing
      effect of arginine with the buffering capacity of histidine. From this final DoE,
      an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at
      a pH of 6.5 was identified to substantially improve stability under long-term
      storage conditions and after multiple freeze/thaw cycles. Thus, our data
      highlights the power of DoE based formulation screening approaches even for
      challenging monoclonal antibody molecules. 

PMID- 27042660
TI  - Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in
      a Rabbit Model.
AB  - Bone defects are repaired using either natural or synthetic bone grafts.
      Poly(epsilon-caprolactone) (PCL), beta-tricalcium phosphate (TCP), and
      poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for
      tissue engineering. This study aimed to investigate the bone-healing capacity of
      PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress
      status of the graft site in a rabbit model. The in vivo performance of 48 healthy
      New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The
      rabbits were assigned to the following groups: group 1 (control), group 2
      (PCL/PLGA hybrid scaffolds), group 3 (PCL/PLGA/TCP hybrid scaffolds), and group 4
      (PCL/PLGA/DB hybrid scaffolds). A 5 mm critical defect was induced in the
      diaphysis of the left radius. X-ray, micro-CT, and histological analyses were
      conducted at (time 0) 4, 8, and 12 weeks after implantation. Furthermore, bone
      formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide
      of type I procollagen, and osteocalcin) were measured and oxidative stress status
      was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed
      that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius
      by inducing repair, suggesting that it could be a good option for the treatment
      of fracture. 

PMID- 27042661
TI  - Current Development in Elderly Comprehensive Assessment and Research Methods.
AB  - Comprehensive geriatric assessment (CGA) is a core and an essential part of the
      comprehensive care of the aging population. CGA uses specific tools to summarize
      elderly status in several domains that may influence the general health and
      outcomes of diseases of elderly patients, including assessment of medical,
      physical, psychological, mental, nutritional, cognitive, social, economic, and
      environmental status. Here, in this paper, we review different assessment tools
      used in elderly patients with chronic diseases. The development of comprehensive
      assessment tools and single assessment tools specially used in a dimension of CGA
      was discussed. CGA provides substantial insight into the comprehensive management
      of elderly patients. Developing concise and effective assessment instruments is
      helpful to carry out CGA widely to create a higher clinical value. 

PMID- 27042662
TI  - Transcatheter Mitral Valve Repair in Surgical High-Risk Patients: Gender-Specific
      Acute and Long-Term Outcomes.
AB  - BACKGROUND: Analyses emphasizing gender-related differences in acute and long
      term outcomes following MitraClip therapy for significant mitral regurgitation
      (MR) are rare. METHODS: 592 consecutive patients (75 +/- 8.7 years, 362 men, 230
      women) underwent clinical and echocardiographic follow-up for a median of 2.13
      (0.99-4.02) years. RESULTS: Significantly higher prevalence of cardiovascular
      comorbidities, renal failure, and adverse echocardiographic parameters in men
      resulted in longer device time (p = 0.007) and higher numbers of implanted clips
      (p = 0.0075), with equal procedural success (p = 1.0). Rehospitalization for
      heart failure did not differ (p[logrank] = 0.288) while survival was higher in
      women (p[logrank] = 0.0317). Logarithmic increase of NT-proBNP was a common
      independent predictor of death. Hypercholesterolemia and peripheral artery
      disease were predictors of death only in men while ischemic and dilative
      cardiomyopathy (CM) and age were predictors in women. Independent predictors of
      rehospitalization for heart failure were severely reduced ejection fraction and
      success in men while both ischemic and dilative CM, logistic EuroSCORE, and MR
      severity were predictive in women. CONCLUSIONS: Higher numbers of implanted clips
      and longer device time are likely related to more comorbidities in men.
      Procedural success and acute and mid-term clinical outcomes were equal. Superior
      survival for women in long-term analysis is presumably attributable to a
      comparatively better preprocedural health.

PMID- 27042663
TI  - Concomitant Thyroid Disorders and Inflammatory Bowel Disease: A Literature
      Review.
AB  - The aim of this report was to review and summarize the literature on cases of
      concomitant inflammatory bowel disease (IBD) and thyroid diseases. We included
      the following previous case reports of concomitant IBD and thyroid diseases: 16
      cases of ulcerative colitis (UC) and Graves' disease (GD), 3 cases of Crohn's
      disease (CD) and GD, 10 cases of CD and Hashimoto's thyroiditis (HT), 4 cases of
      IBD and subacute thyroiditis (SAT) or SAT-like symptoms, and 13 cases of IBD
      (12/13 cases were CD) and amyloid goiter. There might be no obvious differences
      of prevalence of thyroid dysfunction (hyper- or hypothyroidism), GD, and thyroid
      cancer between IBD patients and general populations. However, concomitant UC and
      HT might be relatively common in patients with multiple autoimmune disorders, and
      AG is one of the complications with CD patients. There might be no obvious
      differences of fatal prognoses between IBD patients with thyroid diseases and
      patients with thyroid diseases without IBD. 

PMID- 27042664
TI  - Are Hyoid Bone and Tongue the Risk Factors Contributing to Postoperative Relapse
      for Mandibular Prognathism?
AB  - OBJECTIVE: The purpose of this study was to investigate postoperative stability
      and the correlation between hyoid, tongue, and mandible position following
      surgery for mandibular prognathism. MATERIALS AND METHODS: Thirty-seven patients,
      treated for mandibular prognathism using intraoral vertical ramus osteotomy
      (IVRO), were evaluated cephalometrically. A set of four standardized lateral
      cephalograms were obtained from each subject preoperatively (T1), immediately
      postoperatively (T2), six weeks to three months postoperatively (T3), and more
      than one year postoperatively (T4). The Student t-tests, the Pearson correlation
      coefficient, and the multiple linear regression were used for statistical
      analysis. RESULTS: Immediately after surgery, menton (Me) setback was 12.8 mm,
      hyoid (H) setback was 4.9 mm, and vallecula epiglottica (V) setback was 5.8 mm.
      The postoperative stability significantly correlated (r = -0.512, p < 0.01) with
      the amount of setback. The hyoid bone and tongue did not have significant effects
      on postoperative stability. Multiple linear regression model (R(2) = 0.2658, p <
      0.05) showed predictability: Horizontal Relapse Me (T4-T2) = -6.406 - 0.488Me (T2
      T1) + 0.069H (T2-T1) - 0.0619V (T2-T1). CONCLUSION: Mandibular setback surgery
      may push the hyoid and tongue significantly backward, but this did not correlate
      with mandibular relapse. Postoperative stability significantly correlated with
      the amount of mandibular setback.

PMID- 27042665
TI  - Factors Associated with the Choice of Peritoneal Dialysis in Patients with End
      Stage Renal Disease.
AB  - BACKGROUND: The purpose of this study was to analyze the factors associated with
      receiving peritoneal dialysis (PD) in patients with incident end-stage renal
      disease (ESRD) in a hospital in Southern Taiwan. METHODS: The study included all
      consecutive patients with incident ESRD who participated in a multidisciplinary
      predialysis education (MPE) program and started their first dialysis therapy
      between January 1, 2008, and June 30, 2013, in the study hospital. We provided
      small group teaching sessions to advanced CKD patients and their family to
      enhance understanding of various dialysis modalities. Multivariate logistic
      regression models were used to analyze the association of patient characteristics
      with the chosen dialysis modality. RESULTS: Of the 656 patients, 524 (80%) chose
      hemodialysis and 132 chose PD. Our data showed that young age, high education
      level, and high scores of activities of daily living (ADLs) were positively
      associated with PD treatment. Patients who received small group teaching sessions
      had higher percentages of PD treatment (30.5% versus 19.5%; P = 0.108) and
      preparedness for dialysis (61.1% versus 46.6%; P = 0.090). CONCLUSION: Young age,
      high education level, and high ADL score were positively associated with choosing
      PD. Early creation of vascular access may be a barrier for PD.

PMID- 27042666
TI  - Serum Sialic Acid Level Is Significantly Associated with Nonalcoholic Fatty Liver
      Disease in a Nonobese Chinese Population: A Cross-Sectional Study.
AB  - BACKGROUND/AIM: To investigate the association between serum sialic acid (SA)
      levels and nonalcoholic fatty liver disease (NAFLD) in a nonobese Chinese
      population. METHODS: A cross-sectional study was performed among the 5916 adults
      who took their annual health examinations at International Health Care Center,
      The First Affiliated Hospital, College of Medicine, Zhejiang University, from
      December 2013 to November 2014. RESULTS: A total of 693 (11.71%) subjects
      fulfilled the diagnostic criteria of NAFLD, and NAFLD patients had significantly
      higher serum SA levels than controls (P < 0.001). The prevalence of NAFLD was
      positively associated with serum SA levels (P for trend <0.001). Serum sialic
      acid levels are significantly associated with features of metabolic syndrome (Ps
      < 0.01). Multivariate logistic regression analysis showed that serum SA level was
      significantly associated with risk for NAFLD (odds ratio: 1.018, 95%; confidence
      interval: 1.007-1.030; P = 0.002). CONCLUSIONS: Our results suggest for the first
      time that NAFLD patients had higher serum SA level than controls, and increased
      serum SA level is significantly associated with risk for NAFLD in a large
      nonobese Chinese population.

PMID- 27042667
TI  - The Diagnostic Role of Adiponectin in Pulmonary Embolism.
AB  - BACKGROUND AND AIMS: Pulmonary thromboembolism (PTE) is a frequent disease with
      difficult diagnosis and high mortality. Misdiagnosis occurs in 2/3 patients and
      mortality rates reach up to 30%. The aim of our study was to investigate the role
      of adiponectin used in emergency service in diagnosis of PTE. MATERIALS AND
      METHODS: 95 patients with suspected PTE included in the study. Plasma adiponectin
      and D-dimer levels were measured and chest X-ray and multidetector row computed
      tomography scan obtained. Diagnosis was supported by vascular filling defect on
      tomography. Control group consisted of patients with suspected PTE and normal
      chest computed tomography findings. RESULTS: Mean D-dimer level was 4241.66 +/-
      1082.98 ng/mL in patients and 2211.21 +/- 1765.53 ng/mL in the control group (p
      <= 0.05). Mean adiponectin level was 5.46 +/- 4.39 MUg/mL in patients and 7.68 +/
      4.67 MUg/mL in the control group (p <= 0.05). Wells and Geneva scores were
      higher in patients compared to the control group. CONCLUSIONS: As a result, we
      conclude that lower adiponectin levels have an important role in the diagnosis of
      PTE.

PMID- 27042669
TI  - Is It Time to Phase Out the Austin Moore Hemiarthroplasty? A Propensity Score
      Matched Case Control Comparison versus Cemented Hemiarthroplasty.
AB  - We compared the Austin Moore hemiarthroplasty versus cemented hemiarthroplasties
      using a propensity score matched cased control study. For a consecutive cohort of
      450 patients with displaced intracapsular neck of femur fractures, 128 matched
      cases in each group were selected based on age, gender, walking status, nursing
      home residency, delays in surgery, ASA score, and the Charlson comorbidity score.
      At a mean follow-up of 16.3 months, we evaluated their outcomes. Significantly
      more patients with AMA experienced thigh pain (RR = 3.5, 95% CI: 1.67-7.33, p =
      0.000), overall complications (RR = 4.47, 95% CI: 1.77-11.3, p = 0.000), and
      implant loosening (RR = 8.42, 95% CI: 2.63-26.95, p = 0.000). There were no
      definite cement related deaths in this series. There was no significant
      difference in mortality, walking status, and the number of revisions between the
      groups. We support the routine use of cemented hemiarthroplasty instead of the
      Austin Moore for treating elderlies with displaced intracapsular neck of femur
      fractures.

PMID- 27042668
TI  - Effect of Cigarette Smoke on Wound Healing of the Septal Mucosa of the Rat.
AB  - OBJECTIVES/HYPOTHESIS: Proper wound healing following endoscopic sinus surgery
      (ESS) is influenced by several factors, like cigarette smoke (CS) exposure. This
      study aims to assess the influence of cigarette smoke on the healing of induced
      septal mucosal lesion in rats. METHODS: Unilateral nasal wounds were created by
      means of the interdental brush in seventy-four-week-old male rats. Animals were
      randomly divided into two groups: control group and CS exposure group, each
      comprising 35 animals, divided into five groups (n = 7). Animals were sacrificed
      in groups of seven on day 2 and then on days 5, 14, and 28 and finally on day 42
      following wound induction. RESULTS: Histological analysis of mucosal specimens
      shows important changes at the CS exposure group. Starting with the infiltrates
      of neutrophils, eosinophils, macrophages, and lymphocytes, the histological
      changes were continued with the Goblet cell proliferation, ciliated cells loss,
      fibrosis, and epithelial and subepithelial hypertrophy. CONCLUSION: In this
      experimental model of nasal wound healing we demonstrated the deleterious effects
      of chronic CS exposure. The adverse effects of CS exposure are firstly a
      postponement of the healing process and secondly the persistence of inflammation
      which becomes chronic.

PMID- 27042670
TI  - Does the Length of Elbow Flexors and Visual Feedback Have Effect on Accuracy of
      Isometric Muscle Contraction in Men after Stroke?
AB  - The aim of the study was to determine the effect of different muscle length and
      visual feedback information (VFI) on accuracy of isometric contraction of elbow
      flexors in men after an ischemic stroke (IS). MATERIALS AND METHODS: Maximum
      voluntary muscle contraction force (MVMCF) and accurate determinate muscle force
      (20% of MVMCF) developed during an isometric contraction of elbow flexors in 90
      degrees  and 60 degrees  of elbow flexion were measured by an isokinetic
      dynamometer in healthy subjects (MH, n = 20) and subjects after an IS during
      their postrehabilitation period (MS, n = 20). RESULTS: In order to evaluate the
      accuracy of the isometric contraction of the elbow flexors absolute errors were
      calculated. The absolute errors provided information about the difference between
      determinate and achieved muscle force. CONCLUSIONS: There is a tendency that
      greater absolute errors generating determinate force are made by MH and MS
      subjects in case of a greater elbow flexors length despite presence of VFI.
      Absolute errors also increase in both groups in case of a greater elbow flexors
      length without VFI. MS subjects make greater absolute errors generating
      determinate force without VFI in comparison with MH in shorter elbow flexors
      length.

PMID- 27042671
TI  - TBS Predict Coronary Artery Calcification in Adults.
AB  - PURPOSE: This study analyzes the association between the bony microarchitecture
      score (trabecular bone score, TBS) and coronary artery calcification (CAC) in
      adults undergoing health exams. MATERIALS AND METHODS: We retrospectively
      collected subjects (N = 81) who underwent coronary computed tomography and bone
      mineral density studies simultaneously. CAC was categorized to three levels
      (Group 0, G0, no CAC, score = 0, N = 45; Group 1, G1, moderate CAC, score = 1
      100, N = 17; Group 2, G2, high CAC, score ? 101, N = 19). Multinomial logistic
      regression was used to study the association between TBS and CAC levels. RESULTS:
      CAC is present in 44.4% of the population. Mean TBS +/- SD was 1.399 +/- 0.090.
      Per 1 SD increase in TBS, the unadjusted odds ratio (2.393) of moderate CAC
      compared with no CAC was significantly increased (95% CI, 1.219-4.696, p =
      0.011). However, there has been no association of TBS with high CAC (OR: 1.026,
      95% CI: 0.586-1.797, p = 0.928). These relationships also existed when
      individually adjusted for age, sex, and multiple other covariates. CONCLUSIONS:
      Higher TBS was related to moderate CAC, but not high CAC; a possible explanation
      may be that bone microarchitecture remodeling becomes more active when early
      coronary artery calcification occurs. However, further researches are needed to
      clarify this pathophysiology.

PMID- 27042672
TI  - Analysis of Trunk Rolling Performances by Mattress Mobility Detection System in
      Poststroke Patients: A Pilot Study.
AB  - PURPOSE: The purpose of this study was to investigate the correlation of
      kinematic variables with quality of trunk control in poststroke patients.
      METHODS: This cross-sectional study included stroke subjects with mild to
      moderate motor deficit corresponding to Brunnstrom stages 3-4. Trunk functional
      performance was measured using bed mobility monitor system. All tasks were
      repeated ten times for both directions in each subject. Outcome measurements
      included the movement time and displacement of center of pressure (CoP) from
      supine to side lying and returning. RESULTS: The results revealed that a
      significant longer turning time was observed when turning from the paretic side
      toward the nonparetic side compared to the other direction, with an estimated
      mean difference of 0.427 sec (P = 0.005). We found a significant difference in
      the time of rolling back to supine position between two directions. The
      displacement of CoP in rolling back from side lying on the nonparetic side was
      smaller than that from the paretic side with an estimated mean difference of 
      0.797 cm (P = 0.023). CONCLUSIONS: The impaired trunk mobility was associated
      with increased movement time and decreased displacement of CoP in poststroke
      patients. Trunk rolling performance has potential in assessment of stroke
      patients.

PMID- 27042673
TI  - Time-Dependent Regional Myocardial Strains in Patients with Heart Failure with a
      Preserved Ejection Fraction.
AB  - OBJECTIVES: To better understand the etiology of HFpEF in a controlled human
      population, regional time-varying strains were computed using echocardiography
      speckle tracking in patients with heart failure with a preserved ejection
      fraction and normal subjects. METHODS: Eleven normal volunteers and ten patients
      with echo-graded diastolic dysfunction and symptoms of heart failure were imaged
      with echocardiography and longitudinal, circumferential, and rotational strains
      were determined using speckle-tracking. Diastolic strain rate was also
      determined. Patient demographics and echo-derived flows, volumes, and pressures
      were recorded. RESULTS: Peak longitudinal and circumferential strain was globally
      reduced in patients (p < 0.001), when compared to controls. The patients attained
      peak longitudinal and circumferential strain at a consistently later point in
      systole than controls. Rotational strains were not different in most LV regions.
      Early diastolic strain rate was significantly reduced in the patients (p <
      0.001). LV mass and wall thickness were significantly increased in the patients;
      however ejection fraction was preserved and stroke volume was diminished (p <
      0.001). CONCLUSIONS: This study shows that patients with HFpEF have reduced early
      diastolic strain rate and reduced peak strain that is regionally homogeneous and
      that they also utilize a longer fraction of systole to achieve peak axial
      strains.

PMID- 27042674
TI  - Brief Communication: Maternal Plasma Autoantibodies Screening in Fetal Down
      Syndrome.
AB  - Imbalance in the metabolites levels which can potentially be related to certain
      fetal chromosomal abnormalities can stimulate mother's immune response to produce
      autoantibodies directed against proteins. The aim of the study was to determine
      the concentration of 9000 autoantibodies in maternal plasma to detect fetal Down
      syndrome. Method. We performed 190 amniocenteses and found 10 patients with
      confirmed fetal Down syndrome (15th-18th weeks of gestation). For the purpose of
      our control we chose 11 women without confirmed chromosomal aberration. To assess
      the expression of autoantibodies in the blood plasma, we used a protein
      microarray, which allows for simultaneous determination of 9000 proteins per
      sample. Results. We revealed 213 statistically significant autoantibodies, whose
      expression decreased or increased in the study group with fetal Down syndrome.
      The second step was to create a classifier of Down syndrome pregnancy, which
      includes 14 antibodies. The predictive value of the classifier (specificity and
      sensitivity) is 100%, classification errors, 0%, cross-validation errors, 0%.
      Conclusion. Our findings suggest that the autoantibodies may play a role in the
      pathophysiology of Down syndrome pregnancy. Defining their potential as
      biochemical markers of Down syndrome pregnancy requires further investigation on
      larger group of patients. 

PMID- 27042675
TI  - Miltefosine for Mucosal and Complicated Cutaneous Old World Leishmaniasis: A Case
      Series and Review of the Literature.
AB  - Complicated Old World cutaneous leishmaniasis (OWCL) and Old World mucosal
      leishmaniasis (OWML) constitute an indication for systemic treatment. To date,
      there no controlled clinical studies that compare treatment options for these
      diseases. We compiled a case series of 24 cases successfully treated with
      miltefosine. We conclude that oral miltefosine is an effective treatment option
      for both OWCL and OWML. 

PMID- 27042676
TI  - CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios: better diagnostic markers of
      Alzheimer disease.
AB  - OBJECTIVE: The diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers for
      Alzheimer's disease (AD) must be improved before widespread clinical use. This
      study aimed to determine whether CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios
      are better diagnostic biomarkers of AD during both predementia and dementia
      stages in comparison to CSF Abeta42 alone. METHODS: The study comprised three
      different cohorts (n = 1182) in whom CSF levels of Abeta42, Abeta40, and Abeta38
      were assessed. CSF Abetas were quantified using three different immunoassays
      (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used
      either amyloid ((18)F-flutemetamol) positron emission tomography (PET) imaging (n
      = 215) or clinical diagnosis (n = 967) of well-characterized patients. RESULTS:
      When using three different immunoassays in cases with subjective cognitive
      decline and mild cognitive impairment, the CSF Abeta42/Abeta40 and
      Abeta42/Abeta38 ratios were significantly better predictors of abnormal amyloid
      PET than CSF Abeta42. Lower Abeta42, Abeta42/Abeta40, and Abeta42/Abeta38 ratios,
      but not Abeta40 and Abeta38, correlated with smaller hippocampal volumes measured
      by magnetic resonance imaging. However, lower Abeta38, Abeta40, and Abeta42, but
      not the ratios, correlated with non-AD-specific subcortical changes, that is,
      larger lateral ventricles and white matter lesions. Further, the Abeta42/Abeta40
      and Abeta42/Abeta38 ratios showed increased accuracy compared to Abeta42 when
      distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia
      and subcortical vascular dementia, where all Abetas (including Abeta42) were
      decreased. INTERPRETATION: The CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios are
      significantly better than CSF Abeta42 to detect brain amyloid deposition in
      prodromal AD and to differentiate AD dementia from non-AD dementias. The ratios
      reflect AD-type pathology better, whereas decline in CSF Abeta42 is also
      associated with non-AD subcortical pathologies. These findings strongly suggest
      that the ratios rather than CSF Abeta42 should be used in the clinical work-up of
      AD.

PMID- 27042677
TI  - Insufficient disease inhibition by intrathecal rituximab in progressive multiple
      sclerosis.
AB  - OBJECTIVE: Inaccessibility of the inflammation compartmentalized to the central
      nervous system (CNS) may underlie the lack of efficacy of immunomodulatory
      treatments in progressive multiple sclerosis (MS). The double blind combination
      of Rituximab by IntraVenous and IntraThecAl injection versus placebo in patients
      with Low-Inflammatory SEcondary progressive MS (RIVITALISE; NCT01212094) trial
      was designed to answer: (1) Whether an induction dose of intravenous and
      intrathecal rituximab efficiently depletes CNS B cells? and (2) If so, whether
      this leads to global inhibition of CNS inflammation and slowing of CNS tissue
      destruction? METHODS: Patients aged 18-65 years were randomly assigned to
      rituximab or placebo. Protocol-stipulated interim analysis quantified the
      efficacy of B-cell depletion. RESULTS: The efficacy on cerebrospinal fluid (CSF)
      biomarkers failed to reach criteria for continuation of the trial. B-cell-related
      CSF biomarkers (sCD21 and B-cell activating factor) changed only in the active
      treatment arm. While CSF B cells were killed robustly (median -79.71%, P =
      0.0176), B cells in CNS tissue were depleted inadequately (~-10-20%, P < 0.0001).
      Consequently, the T-cell-specific CSF biomarker sCD27 decreased slightly (
      10.97%, P = 0.0005), while axonal damage marker, neurofilament light chain did
      not change. Insufficient saturation of CD20, lack of lytic complement, and
      paucity of cytotoxic CD56(dim) NK cells contribute to decreased efficacy of
      rituximab in the CNS. INTERPRETATION: Biomarker studies reliably quantified
      complementary pharmacodynamic effects of rituximab in the CNS, exposed causes for
      poor efficacy and determined that RIVITALISE trial would be underpowered to
      measure efficacy on clinical outcomes. Identified mechanisms for poor efficacy
      are applicable to all CNS-inflammation targeting monoclonal antibodies.

PMID- 27042678
TI  - Rapamycin prevents acute dendritic injury following seizures.
AB  - OBJECTIVE: Seizures cause acute structural changes in dendrites, which may
      contribute to cognitive deficits that occur in epilepsy patients. Disruption of
      the actin cytoskeleton of dendrites likely mediates the structural changes
      following seizures, but the upstream signaling mechanisms activated by
      synchronized physiological activity to cause seizure-induced dendritic injury are
      not known. In this study, we test the hypothesis that the mechanistic target of
      rapamycin complex 1 (mTORC1) pathway triggers structural changes in dendrites in
      response to seizures. METHODS: In vivo multiphoton imaging was performed in
      transgenic mice expressing green fluorescent protein in cortical neurons. The
      effect of rapamycin pre- and posttreatment was tested on kainate-induced
      dendritic injury and cofilin-mediated actin depolymerization. RESULTS: Kainate
      induced seizures caused acute activation of mTORC1 activity, which was prevented
      by the mTORC1 inhibitor, rapamycin. Rapamycin pretreatment, and to a lesser
      degree, posttreatment attenuated acute seizure-induced dendritic injury and
      correspondingly decreased LIM kinase and cofilin-mediated depolymerization of
      actin. INTERPRETATION: The mTORC1 pathway mediates seizure-induced dendritic
      injury via depolymerization of actin. These findings have important mechanistic
      and translational applications for management of seizure-induced brain injury.

PMID- 27042679
TI  - Parkinson disease and progressive supranuclear palsy: protein expression in skin.
AB  - OBJECTIVE: This study characterizes the expression of tau (p-tau) and alpha
      synuclein (alpha-syn) by immunohistochemistry in the skin of three different
      populations: healthy control (HC), Parkinson disease (PD), and progressive
      supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker
      that could differentiate between subjects with PD and PSP. MATERIAL AND METHODS:
      We evaluated the presence of p-tau and alpha-syn in a pilot study in the skin of
      three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and
      10 patients with PSP. Four millimeters punch biopsies were obtained from the
      occipital area and analyzed by immunohistochemistry using antibodies against
      alpha-syn and phosphorylated species of tau. PHF (paired helical filaments)
      antibody identifies p-tau in both normal and pathological conditions and AT8
      recognizes p-tau characteristic of pathological conditions. Differences between
      the three groups were assessed by quantification of immunopositive areas in the
      epidermis. RESULTS: The immunopositivity pattern of p-tau and alpha-syn was
      significantly different among the three groups. Healthy subjects showed minimal
      staining using AT8 and alpha-syn. The PD group showed significantly higher alpha
      syn and AT8 immunopositivity, while the PSP group only expressed higher AT8
      immunopositivity than HCs. CONCLUSION: These data suggest that the skin reflects
      brain pathology. Therefore, immunohistochemical analysis of p-tau and alpha-syn
      in the skin can be useful for further characterization of PD and PSP.

PMID- 27042680
TI  - Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study.
AB  - OBJECTIVE: Gaucher disease (GD) is a lysosomal storage disease characterized by a
      deficiency of glucocerebrosidase. Although enzyme-replacement and substrate
      reduction therapies are available, their efficacies in treating the neurological
      manifestations of GD are negligible. Pharmacological chaperone therapy is
      hypothesized to offer a new strategy for treating the neurological manifestations
      of this disease. Specifically, ambroxol, a commonly used expectorant, has been
      proposed as a candidate pharmacological chaperone. The purpose of this study was
      to evaluate the safety, tolerability, and neurological efficacy of ambroxol in
      patients with neuronopathic GD. METHODS: This open-label pilot study included
      five patients who received high-dose oral ambroxol in combination with enzyme
      replacement therapy. Safety was assessed by adverse event query, physical
      examination, electrocardiography, laboratory studies, and drug concentration.
      Biochemical efficacy was assessed through evidence of glucocerebrosidase activity
      in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid.
      Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale,
      Gross Motor Function Measure, Functional Independence Measure, seizure frequency,
      pupillary light reflex, horizontal saccadic latency, and electrophysiologic
      studies. RESULTS: High-dose oral ambroxol had good safety and tolerability,
      significantly increased lymphocyte glucocerebrosidase activity, permeated the
      blood-brain barrier, and decreased glucosylsphingosine levels in the
      cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction
      markedly improved in all patients. Relief from myoclonus led to impressive
      recovery of gross motor function in two patients, allowing them to walk again.
      INTERPRETATION: Pharmacological chaperone therapy with high-dose oral ambroxol
      shows promise in treating neuronopathic GD, necessitating further clinical
      trials.

PMID- 27042681
TI  - Plasma neurofilament light chain predicts progression in progressive supranuclear
      palsy.
AB  - OBJECTIVE: Blood-based biomarkers for neurodegenerative conditions could improve
      diagnosis and treatment development. Neurofilament light chain (NfL), a marker of
      axonal injury, is elevated in cerebrospinal fluid (CSF) of patients with
      progressive supranuclear palsy (PSP). The goal of this study was to determine the
      diagnostic and prognostic value of plasma NfL in patients with PSP. METHODS:
      Plasma NfL was measured with ultrasensitive digital immunoassay-based technology
      at baseline and 1-year follow-up in a pilot cohort of 15 PSP patients and 12
      healthy controls, and a validation cohort of 147 PSP patients. Mixed linear
      models tested the ability of plasma NfL to predict neurological, cognitive and
      functional decline, and brain atrophy. RESULTS: Baseline mean plasma NfL levels
      were elevated in PSP patients (31 +/- 4 pg/mL, vs. control, 17.5 +/- 1 pg/mL, P <
      0.05) and this difference persisted at follow-up. A cutoff value of 20 pg/mL
      related to the diagnosis of PSP with a sensitivity of 0.80 and specificity of
      0.83 (positive likelihood ratio = 4.7 and a negative likelihood radio of 0.24).
      Patients with higher NfL levels had more severe neurological (PSPRS, -36.9% vs. 
      28.9%, P = 0.04), functional (SEADL, -38.2% vs. -20%, P = 0.03), and
      neuropsychological (RBANS, -23.9% vs. -12.3%, P = 001) deterioration over 1 year.
      Higher baseline NfL predicted greater whole-brain and superior cerebellar
      peduncle volume loss. Plasma and CSF NfL were significantly correlated (r = 0.74,
      P = 0.002). INTERPRETATION: Plasma NfL is elevated in PSP and could be of value
      as a biomarker both to assist clinical diagnosis and to monitor pharmacodynamic
      effects on the neurodegenerative process in clinical trials.

PMID- 27042682
TI  - Progressive multifocal leukoencephalopathy in an immunocompetent patient.
AB  - Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the
      brain, is typically diagnosed in immunocompromised persons. Here, we describe the
      diagnostic challenge of PML in an apparently immunocompetent patient. Thorough
      analyses, including cytokine release assays and whole exome sequencing, revealed
      a deficit in the antiviral interferon gamma production capacity of this patient
      and compound heterozygous mutations in BCL-2-associated athanogene 3.
      Interestingly, both factors are associated with reduced expression of John
      Cunningham virus T-antigen, a protein that plays a key role in viral replication
      in infected cells. After validation in other patients, our findings may
      contribute to novel insights into the etiology and possibly treatment of PML.

PMID- 27042684
TI  - James Webb Space Telescope segment phasing using differential optical transfer
      functions.
AB  - Differential optical transfer function (dOTF) is an image-based, noniterative
      wavefront sensing method that uses two star images with a single small change in
      the pupil. We describe two possible methods for introducing the required pupil
      modification to the James Webb Space Telescope, one using a small (<lambda/4)
      displacement of a single segment's actuator and another that uses small
      misalignments of the NIRCam's filter wheel. While both methods should work with
      NIRCam, the actuator method will allow both MIRI and NIRISS to be used for
      segment phasing, which is a new functionality. Since the actuator method requires
      only small displacements, it should provide a fast and safe phasing alternative
      that reduces the mission risk and can be performed frequently for alignment
      monitoring and maintenance. Since a single actuator modification can be seen by
      all three cameras, it should be possible to calibrate the non-common-path
      aberrations between them. Large segment discontinuities can be measured using
      dOTFs in two filter bands. Using two images of a star field, aberrations along
      multiple lines of sight through the telescope can be measured simultaneously.
      Also, since dOTF gives the pupil field amplitude as well as the phase, it could
      provide a first approximation or constraint to the planned iterative phase
      retrieval algorithms.

PMID- 27042683
TI  - Structural connectivity analyses in motor recovery research after stroke.
AB  - Structural connectivity analyses by means of diffusion-weighted imaging have
      substantially advanced the understanding of stroke-related network alterations
      and their implications for motor recovery processes and residual motor function.
      Analyses of the corticospinal tract, alternate corticofugal pathways as well as
      intrahemispheric and interhemispheric corticocortical connections have not only
      been related to residual motor function in cross-sectional studies, but have also
      been evaluated to predict functional recovery after stroke in longitudinal
      studies. This review will consist of an update on the available literature about
      structural connectivity analyses after ischemic motor stroke, followed by an
      outlook of possible future directions of research and applications.

PMID- 27042685
TI  - Preface to Special Topic on Protein Dynamics: Beyond Static Snapshots in
      Structural Biology.

PMID- 27042686
TI  - Tandem Affinity Purification in Drosophila Heads and Ovaries.
AB  - Tandem affinity purification (TAP) (Pugi et al., 2001; Rigaut et al., 1999) is a
      method that uses a tagging approach of a target protein of interest for a two
      step purification scheme in order to pull down protein complexes under native
      conditions and expression levels. The TAP tag consists of three components: a
      calmodulin-binding peptide, a Tobacco etch virus (TEV) protease cleavage site and
      Protein A which is an immunoglobulin G (IgG)-binding domain. This protocol was
      modified from the original methodology used in yeast cells (Pugi et al., 2001;
      Rigaut et al., 1999) for isolation of protein complexes from Drosophila heads and
      ovaries expressing a TAP tagged protein of interest. To determine in vivo binding
      partners of the Drosophila fragile X protein (dFMR1), we developed a transgenic
      strain of flies expressing a recombinant form of dFMR1 with a carboxy-terminal
      TAP tag (Tsai and Carstens, 2006). To ensure that the construct was expressed at
      wild-type levels, we engineered this form of the tagged protein in the context of
      a genomic rescue construct that rescued a mutant sterility phenotype. The
      purification process was performed using mild conditions to maintain native
      protein interactions. For TAP methods in Drosophila S2 cell culture, we have
      successfully used a protocol previously published by Tsai and Carstens (Tsai and
      Carstens, 2006; Bhogal et al., 2011).

PMID- 27042687
TI  - MEDICARE PAYMENTS AND SYSTEM-LEVEL HEALTH-CARE USE: The Spillover Effects of
      Medicare Managed Care.
AB  - The rapid growth of Medicare managed care over the past decade has the potential
      to increase the efficiency of health-care delivery. Improvements in care
      management for some may improve efficiency system-wide, with implications for
      optimal payment policy in public insurance programs. These system-level effects
      may depend on local health-care market structure and vary based on patient
      characteristics. We use exogenous variation in the Medicare payment schedule to
      isolate the effects of market-level managed care enrollment on the quantity and
      quality of care delivered. We find that in areas with greater enrollment of
      Medicare beneficiaries in managed care, the non-managed care beneficiaries have
      fewer days in the hospital but more outpatient visits, consistent with a
      substitution of less expensive outpatient care for more expensive inpatient care,
      particularly at high levels of managed care. We find no evidence that care is of
      lower quality. Optimal payment policies for Medicare managed care enrollees that
      account for system-level spillovers may thus be higher than those that do not.

PMID- 27042688
TI  - Smokers' Early E-cigarette Experiences, Reasons for Use, and Use Intentions.
AB  - OBJECTIVES: This study examined the context of smokers' first e-cigarette
      experiences, reasons for trying e-cigarettes, not continuing their use, and
      future use intentions. METHODS: We surveyed a nationally representative sample of
      519 current cigarette smokers in the United States (classified as never, current,
      or former e-cigarette users/triers) in April 2014 about their e-cigarette
      experiences and use intentions. RESULTS: Among ever e-cigarette users/triers, 43%
      purchased an e-cigarette on their own as their first method of trial. These
      respondents were more likely to have used e-cigarettes more times than those who
      first tried e-cigarettes from a friend. Positive perceptions about first
      experiences were significantly higher among current (34.5%) compared to former e
      cigarette users/triers (17.9%). Few (8.7%) current e-cigarette users/triers had a
      negative first experience. Susceptibility to future e-cigarette use was
      significantly associated with e-cigarette use status, intention to quit smoking
      and satisfaction with first e-cigarette experience. Among those interested in e
      cigarettes, 26.3% were more interested in trying an e-cigarette made by a major
      tobacco company and 31.8% in trying an e-cigarette that looked "similar" versus
      different (13.8%) than a real cigarette. CONCLUSIONS: The context and perceptions
      of e-cigarette trial experiences, product quality, style and manufacturer may
      influence e-cigarette trial and use.

PMID- 27042689
TI  - Social Media, Big Data, and Mental Health: Current Advances and Ethical
      Implications.
AB  - Mental health (including substance abuse) is the fifth greatest contributor to
      the global burden of disease, with an economic cost estimated to be US $2.5
      trillion in 2010, and expected to double by 2030. Developing information systems
      to support and strengthen population-level mental health monitoring forms a core
      part of the World Health Organization's Comprehensive Action Plan 2013-2020. In
      this paper, we review recent work that utilizes social media "big data" in
      conjunction with associated technologies like natural language processing and
      machine learning to address pressing problems in population-level mental health
      surveillance and research, focusing both on technological advances and core
      ethical challenges.

PMID- 27042690
TI  - Retracted: Bacterial Biodegradation of Crude Oil Using Local Isolates.
AB  - [This retracts the article DOI: 10.1155/2014/863272.]. 

PMID- 27042691
TI  - Anthranilic Acid: A Potential Biomarker and Treatment Target for Schizophrenia.
AB  - Dysregulation of Trp-Kyn pathway is the most recent hypothesis of mechanisms of
      schizophrenia. In particular, over-production of kynurenic acid (KYNA), one of
      the three immediate downstream metabolites of kynurenine (Kyn) along tryptophan
      (Trp): Kyn pathway, has been considered as a new target for therapeutic
      intervention in schizophrenia. Up-regulation of KYNA formation was suggested to
      occur at the expense of down-regulated production of 3-hydroxyKyn (3-HK), the
      second immediate downstream metabolite of Kyn. We were interested to assess the
      third immediate downstream Kyn metabolite, anthranilic acid (AA). Serum AA
      concentrations were evaluated in schizophrenia patients and control subjects by
      HPLC-mass spectrometry method. We found 2-fold increase of AA and 3-fold decrease
      of 3-HK concentrations in serum of schizophrenia patients. Up regulated formation
      of AA might contribute to mechanisms of schizophrenia considering experimental
      evidences of AA augmentation of autoimmune processes in rat and mice; clinical
      findings of AA elevation in rheumatoid arthritis and type 1 diabetes, autoimmune
      diseases diametrical to schizophrenia; and involvement of autoimmunity in
      development of schizophrenia. Present data warrant further studies of AA as
      biological marker in, at least, a subgroup (associated with autoimmune
      mechanisms) of schizophrenia patients and as a new target for therapeutic
      intervention.

PMID- 27042692
TI  - Methylene blue treatment in experimental ischemic stroke: a mini review.
AB  - Stroke is a leading cause of death and long-term disability. Methylene blue, a
      drug grandfathered by the Food and Drug Administration with a long history of
      safe usage in humans for treating methemoglobinemia and cyanide poisoning, has
      recently been shown to be neuroprotective in neurodegenerative diseases and brain
      injuries. The goal of this paper is to review studies on methylene blue in
      experimental stroke models.

PMID- 27042693
TI  - STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND
      SIMILARITIES BETWEEN ATRIA AND VENTRICLES.
AB  - Evidence accumulated over the last 25 years suggests that, whether in the atria
      or ventricles, fibrillation may be explained by the self-organization of the
      cardiac electrical activity into rapidly spinning rotors giving way to spiral
      waves that break intermittently and result in fibrillatory conduction. The
      dynamics and frequency of such rotors depend on the ion channel composition,
      excitability and refractory properties of the tissues involved, as well as on the
      thickness and respective three-dimensional fiber structure of the atrial and
      ventricular chambers. Therefore, improving the understanding of fibrillation has
      required the use of multidisciplinary research approaches, including optical
      mapping, patch clamping and molecular biology, and the application of concepts
      derived from the theory of wave propagation in excitable media. Moreover,
      translation of such concepts to the clinic has recently opened new opportunities
      to apply novel mechanistic approaches to therapy, particularly during atrial
      fibrillation ablation. Here we review the current understanding of the manner in
      which the underlying myocardial structure and function influence rotor initiation
      and maintenance during cardiac fibrillation. We also examine relevant underlying
      differences and similarities between atrial fibrillation and ventricular
      fibrillation and evaluate the latest clinical mapping technologies used to
      identify rotors in either arrhythmia. Altogether, the data being discussed have
      significantly improved our understanding of the cellular and structural bases of
      cardiac fibrillation and pointed toward potentially exciting new avenues for more
      efficient and effective identification and therapy of the most complex cardiac
      arrhythmias.

PMID- 27042694
TI  - Probing the Fifty Shades of EMT in Metastasis.
AB  - The involvement of epithelial-to-mesenchymal transition (EMT) in metastasis has
      long been under debate. Recent efforts to probe the occurrence and functional
      significance of EMT in clinical samples and animal models have produced exciting
      but sometimes conflicting findings. The diversity of EMT underlies the challenge
      in studying its role in metastasis.

PMID- 27042695
TI  - Examining maternal beliefs and human papillomavirus vaccine uptake among male and
      female children in low-income families.
AB  - PURPOSE: This study examines within-family differences in the uptake of the HPV
      vaccine and HPV-related beliefs by children's sex. METHODS: From a 2011-2013
      survey of mothers of children aged 9-17 years in Texas, mothers with both male
      and female children (n=350) were selected. RESULTS: Mothers were more likely to
      report having initiated and completed HPV vaccination for their daughters than
      sons. Mothers did not express differences by children's sex in HPV-related
      beliefs. Among those who had not completely vaccinated either child, mothers were
      more likely to report they wanted their daughters compared to sons vaccinated and
      were more likely to report feeling confident they could get their daughters
      vaccinated than their sons. CONCLUSION: In this population, mothers were more
      likely to report HPV vaccination of and motivation to vaccinate daughters
      compared to sons, although maternal beliefs about HPV did not differ by
      children's sex.

PMID- 27042696
TI  - Terricolous lichens in the glacier forefield of the Matscherferner (Eastern Alps,
      South Tyrol, Italy).
AB  - Two sampling sites were established at increasing distance from the glacier to
      investigate lichen communities on soil, plant debris and terricolous mosses in
      the glacier forefield of the Matscherferner. The survey yielded 34 lichen species
      and one lichenicolous fungus. In addition, 19 lichen species and one
      lichenicolous fungus were found by collecting at random, outside the two sampling
      sites.

PMID- 27042697
TI  - Differential nuclear staining assay for high-throughput screening to identify
      cytotoxic compounds.
AB  - As large quantities of novel synthetic molecules continue to be generated there
      is a challenge to identify therapeutic agents with cytotoxic activity. Here we
      introduce a Differential Nuclear Staining (DNS) assay adapted to live-cell
      imaging for high throughput screening (HTS) that utilizes two fluorescent DNA
      intercalators, Hoechst 33342 and Propidium iodide (PI). Since Hoechst can readily
      cross cell membranes to stain DNA of living and dead cells, it was used to label
      the total number of cells. In contrast, PI only enters cells with compromised
      plasma membranes, thus selectively labeling dead cells. The DNS assay was
      successfully validated by utilizing well known cytotoxic agents with fast or slow
      cytotoxic activities. The assay was found to be suitable for HTS with Z' factors
      ranging from 0.86 to 0.60 for 96 and 384-well formats, respectively. Furthermore,
      besides plate-to-plate reproducibility, assay quality performance was evaluated
      by determining ratios of signal-to-noise and signal-to-background, as well as
      coefficient of variation, which resulted in adequate values and validated the
      assay for HTS initiatives. As proof of concept, eighty structurally diverse
      compounds from a small molecule library were screened in a 96-well plate format
      using the DNS assay. Using this DNS assay, six hits with cytotoxic properties
      were identified and all of them were also successfully identified by using the
      commercially available MTS assay (CellTiter 96(r) Cell Proliferation Assay). In
      addition, the DNS and a flow cytometry assay were used to validate the activity
      of the cytotoxic compounds. The DNS assay was also used to generate dose-response
      curves and to obtain CC50 values. The results indicate that the DNS assay is
      reliable and robust and suitable for primary and secondary screens of compounds
      with potential cytotoxic activity.

PMID- 27042698
TI  - Oral Feeding Assessment Predicts Length of Hospital Stay in Late Preterm Infants.
AB  - BACKGROUND: When compared with term infants, late preterm (LP) infants have
      greater morbidity and mortality, longer hospital stay, and greater rate of
      hospital readmission. Oral feeding difficulty is one of the prominent reasons for
      delayed discharge in LP infants. OBJECTIVE: To identify the maturity levels of LP
      infants' oral feeding skills (OFS) at the time of their first oral feeding and to
      determine the relationship between OFS maturity levels and length of hospital
      stay. METHODS: OFS was assessed in 48 LP infants born between 340/7 and 356/7
      weeks gestational age at the time of their first oral feeding within 24 h of
      birth. The intake at 5 minutes, at completion of the feeding, and the duration of
      feeding a 15 mL prescribed volume of milk were tabulated. Proficiency expressed
      as percent mL consumed in the first 5 min/15 mL prescribed and rate of milk
      transfer over the entire feeding (mL/min) were recorded. OFS were assessed using
      a novel 4-level scale defined by the combined proficiency and rate of milk
      transfer. RESULTS: When compared with their 35-week counterparts, infants born at
      34 weeks gestation had poorer OFS profiles (p = 0.035) and longer hospital stay
      (p < 0.001). Additionally, further analyses demonstrated that, independently, LOS
      was associated negatively with both GA and OFS. CONCLUSION: Assessment of OFS
      levels in LP infants at their first oral feeding can help identify infants at
      risk of oral feeding issues that may delay hospital discharge. For those infants,
      we speculate that provision of evidence-based efficacious interventions that
      improve OFS may shorten hospital stay and decrease hospital re-admissions.

PMID- 27042699
TI  - Proteomics Characterization of Primary Human Oral Epithelial Cells Using a Novel
      Culture Technique for Use in Tissue Regeneration.
AB  - Oral mucosa keratinocytes are widely used in regenerative medicine. The unique
      cultured cell population "Epithelial-derived Pop-Up Keratinocytes (ePUKs)" was
      previously reported as undifferentiated cells. Gravity Assisted Cell Sorting
      (GACS) was used to isolate a small-sized population of undifferentiated cells
      enriched ePUKs. LC/MS/MS analysis was performed to define the cellular profile of
      ePUKs of primary human oral mucosa keratinocytes. Small sized ePUKs which showed
      increased expression of Dickkopf WNT signaling pathway inhibitor 1 (DKK1), serpin
      peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1),
      member 1 (SERPINE1), follistatin and tenascin-C were verified by Western blots.
      These proteins are involved in the regulation of cellular movement, hair follicle
      development and the maintenance of its stem cell niche. The fabrication of a
      tissue-engineered oral mucosa, ex vivo produced oral mucosa equivalent (EVPOME),
      using ePUKs showed increased abundance of these verified proteins. These findings
      indicate that the specific phenotype of ePUKs and their ability to influence
      wound healing promotion are implicated by highly expressed cellular movement
      regulatory proteins. Therefore, ePUKs may be a useful cell source for use in
      regenerative medicine.

PMID- 27042700
TI  - A Longitudinal Support Vector Regression for Prediction of ALS Score.
AB  - Longitudinal studies play a key role in various fields, including epidemiology,
      clinical research, and genomic analysis. Currently, the most popular methods in
      longitudinal data analysis are model-driven regression approaches, which impose
      strong prior assumptions and are unable to scale to large problems in the manner
      of machine learning algorithms. In this work, we propose a novel longitudinal
      support vector regression (LSVR) algorithm that not only takes the advantage of
      one of the most popular machine learning methods, but also is able to model the
      temporal nature of longitudinal data by taking into account observational
      dependence within subjects. We test LSVR on publicly available data from the
      DREAM-Phil Bowen ALS Prediction Prize4Life challenge. Results suggest that LSVR
      is at a minimum competitive with favored machine learning methods and is able to
      outperform those methods in predicting ALS score one month in advance.

PMID- 27042701
TI  - Age, Race and Regional Disparities in Colorectal Cancer Incidence Rates in
      Georgia between 2000 and 2012.
AB  - Colorectal cancer (CRC) incidence rates and mortality have been decreasing in the
      United States. Currently, states in the South have the smallest reduction in CRC
      mortality. The trends of CRC incidence rates in Georgia in comparison to the
      United States have not been investigated. We analyzed age-adjusted incidence
      rates of CRC in Georgia and the United States from 2000 to 2012 using data from
      SEER 18 registries. Age-adjusted incidence rates (95% CI) were calculated as
      cases per 100,000 to the 2000 US Standard population. CRC incidence rates were
      calculated for groupings based on age at time of diagnosis, race, sex, and
      geographic location within Georgia. Incidence rates were higher in males compared
      to females in Georgia. In Georgians age 50-64, incidence rates were higher
      compared to the US, while those ages 65+ displayed lower incidence rates. Black
      Georgians age 50-64 generally exhibited higher incidence rates of CRC and lower
      rates of decrease in incidence compared to other races in Georgia. Asian/Pacific
      Islander females age 50-64 in Georgia exhibited an increasing trend in incidence
      rate. Whites and blacks Georgians age 50-64 displayed higher incidence rates
      compared to the US, while Asian/Pacific Islanders displayed lower incidence
      rates. Greater incidence rates of CRC in rural and Greater Georgia were seen
      across all races when compared to overall rates in Georgia. Efforts should be
      made to address disparities in Georgia based on race and geographic location.
      Increased screening by colonoscopy or fecal occult blood testing, reduction of
      risk factors and promotion of healthy lifestyles can reduce CRC incidence rates.

PMID- 27042702
TI  - Reducing Stress and Preventing Anxiety in African American Adolescents: A
      Culturally- Grounded Approach.
AB  - Evidenced-based and culturally adapted stress-reduction interventions for urban
      African American adolescents who are at risk for anxiety and other problems
      related to stress are needed. This study presents intervention components and
      preliminary outcome findings of a culturally adapted stress-reduction
      intervention for urban African American adolescents. Preliminary findings support
      the efficacy of the intervention to reduce anxiety and enhance general cognitive
      competencies, such as coping strategies, self-efficacy, and positive thinking,
      among participants, in comparison to controls. Clinical implications of the
      stress-reduction intervention for the prevention of psychopathology, particularly
      among African American adolescents, are discussed.

PMID- 27042703
TI  - Effect of Bulk-filling on the Bonding Efficacy in Occlusal Class I Cavities.
AB  - PURPOSE: To evaluate the effect of bulk filling Class I posterior cavities on
      bonding to cavity-bottom dentin. MATERIALS AND METHODS: Two flowable "base" bulk
      fill composites (Filtek Bulk Fill Flowable, SDR), one paste-like "full-body" bulk
      fill composite (Tetric EvoCeram Bulk Fill) and one conventional paste-like
      composite (Filtek Z100) were bonded (G-aenial Bond) to either a flat surface (3.5
      x 3.5 x 4 mm; C-factor: 0.18) or a Class I cavity (3.5 x 3.5 x 4 mm; C-factor:
      5.8). After 1-week water storage, the restorations were sectioned to obtain 4
      rectangular microspecimens that were subjected to microtensile bond strength
      (MUTBS) testing. RESULTS: No significant differences in MUTBS were recorded
      between all composites when bonded onto a flat surface (p > 0.05). When bonded
      into a Class I cavity, the MUTBS of all composites except SDR significantly
      decreased (p < 0.001). CONCLUSION: Both the configuration factor and the type of
      bulk-fill composite were found to have a great impact on bonding to cavity-bottom
      dentin.

PMID- 27042704
TI  - Cytotoxic Effects of One-step Self-etching Dental Adhesives on Human Periodontal
      Ligament Fibroblasts In Vitro.
AB  - PURPOSE: To evaluate the potential cytotoxic effects of four one-step self
      etching dental adhesives [Adper Easy One (AEO), iBond (IB), Clearfil S3 Bond
      (CSB), and G-Bond (GB)] on cultured human periodontal ligament fibroblasts.
      MATERIALS AND METHODS: Cured adhesives were immersed in complete DMEM or
      deionized water and maintained at 37 degrees C for 24 h, followed by
      sterilization. The deionized water-based extract was used for Fourier transform
      infrared spectroscopy analysis. The DMEM-based extract was diluted into various
      concentrations for cytotoxicity tests. The viability, integrity, and apoptosis of
      cultured human periodontal ligament fibroblasts upon treatment with the extracts
      were determined using the CCK-8 assay, microscopy, and flow cytometry. RESULTS:
      All of the four adhesives induced cell viability loss, cell morphology
      alteration, and cell death. GB showed the greatest cytotoxicity by inducing cell
      apoptosis and necrosis, while IB had the weakest cytotoxic effect on the cultured
      cells. CONCLUSION: All tested dental adhesives have significant adverse effects
      on cell viability. Therefore, precautions should be taken to protect the
      periodontal tissues when dental adhesives are applied in the clinic.

PMID- 27042705
TI  - Effect of Silane Reaction Time on the Repair of a Nanofilled Composite Using
      Tribochemical Treatment.
AB  - PURPOSE: To investigate the influence of silane reaction time on the repair
      strength of an aged nanofilled composite and to characterize the bonding
      mechanism. MATERIALS AND METHODS: Nanofilled composite disks (n = 110, Filtek
      Supreme XT) were aged for 90 days in water. After tribochemical treatment (CoJet
      Sand), the specimens were assigned to 5 groups (n = 22), primed with silane (Espe
      Sil), and left to react for 1, 2, 3, 4, and 5 min. A thin layer of adhesive
      (Visio-Bond) was applied and a new composite with the same dimension was placed
      and cured. Non-aged specimens immediately layered and cured using the incremental
      technique served as controls. After aging (30 days in water plus 5000 thermal
      cycles), the interface was subjected to a shearing force until failure. Failure
      mode was evaluated under a stereomicroscope and scanning electron microscopy
      (SEM). Additional aged and treated surfaces were evaluated for morphology as well
      as elemental and molecular composition using SEM/EDX and ATR-FTIR. RESULTS: The
      mean shear bond strength (SBS) of the repaired specimens was 53.9 +/- 8.6 MPa,
      with no significant difference among the various reaction times, but
      significantly lower compared to the control (88.1 +/- 12.5 MPa). Tribochemical
      treatment created an irregular surface morphology with particles imbedded in the
      aged surface. Interfacial SEM/EDX analysis showed a 5-MUm non-uniform high atomic
      number zone rich in Al and Si. CONCLUSION: Tribochemical treatments for repairing
      composite using a short silane reaction period (1 min) are equally effective as
      the prolonged reaction periods (2 to 5 min), yielding interfacial shear strength
      of ~60% of unrepaired material.

PMID- 27042706
TI  - Fracture Strength of Endodontically Treated Teeth Restored with Composite
      Overlays with and without Glass-fiber Reinforcement.
AB  - PURPOSE: To evaluate the fracture strength and the failure mode of endodontically
      treated teeth restored with composite resin overlays with and without glass-fiber
      reinforcement. MATERIALS AND METHODS: A total of 32 extracted molars were divided
      into four equal groups. In the NFR-NFRC (no foundation restoration, no fiber
      reinforced composite) and NFR-FRC (no foundation restoration, fiber-reinforced
      composite) groups, only a 5-mm-thick composite resin layer sealed the pulp
      chamber floors, whereas in the FR-NFRC (foundation restoration, no fiber
      reinforced composite) and FR-FRC (foundation restoration, fiber-reinforced
      composite) groups, a 3.0-mm foundation restoration was used. NFR-NFRC and FR-NFRC
      groups were restored with composite resin overlays, whereas NFR-FRC and FR-FRC
      groups were restored with fiber-reinforced composite resin overlays. All
      specimens were subjected to mechanical loading in a computer-controlled
      masticator and then the fracture resistance was evaluated. Differences in means
      were compared using two-way ANOVA and Tukey's test. The level of significance was
      set at alpha = 0.05. RESULTS: All specimens successfully completed the fatigue
      test. The least fracture-resistant group was NFR-FRC, exceeded by FR-NFRC, NFR
      NFRC, and FR-FRC, in that order, with FR-FRC being the most fracture-resistant
      group. Statistically significant differences were detected between the pairs NFR
      NFRC/FR-FRC (p = 0.001), NFR-FRC/FR-FRC (p = 0.001), and FR-NFRC/FR-FRC (p =
      0.001). Eight vertical root fractures occurred in group FR-NFRC, six in group NFR
      NFRC, four in group NFR-FRC, and none occurred in group FR-FRC. CONCLUSIONS:
      Within the limitations of this in vitro study, the incorporation of glass fibers
      and the presence of a foundation restoration were found to increase the fracture
      resistance and can favorably influence the fracture mode.

PMID- 27042708
TI  - Creation of hollow SAPO-34 single crystals via alkaline or acid etching.
AB  - Hollow SAPO-34 crystals are created via selective etching of their precursor
      under controlled alkaline or acid conditions. The abundant/interconnected Si-O-Al
      domains and Si-O-Si networks at the outer layer of SAPO-34 crystals are revealed
      to be decisive factors for the base and acid treatments respectively to achieve a
      well-preserved hollow structure. 

PMID- 27042707
TI  - Influence of Surface Conditioning Protocols on Reparability of CAD/CAM Zirconia
      reinforced Lithium Silicate Ceramic.
AB  - PURPOSE: To test the effect of surface conditioning protocols on the reparability
      of CAD/CAM zirconia-reinforced lithium silicate ceramic compared to lithium
      disilicate glass ceramic. MATERIALS AND METHODS: Zirconia-reinforced lithium
      silicate ceramic (Vita Suprinity) and lithium disilicate glass-ceramic blocks
      (IPS e.max CAD) were categorized into four groups based on the surface
      conditioning protocol used. Group C: no treatment (control); group HF: 5%
      hydrofluoric acid etching for 60 s, silane (Monobond-S) application for 60 s, air
      drying; group HF-H: 5% HF acid etching for 60 s, application of silane for 60 s,
      air drying, application of Heliobond, light curing for 20 s; group CO:
      sandblasting with CoJet sand followed by silanization. Composite resin (Tetric
      EvoCeram) was built up into 4 x 6 x 3 mm blocks using teflon molds. All specimens
      were subjected to thermocycling (5000x, 5 degrees C to 55 degrees C). The
      microtensile bond strength test was employed at a crosshead speed of 1 mm/min.
      SEM was employed for evaluation of all the debonded microbars, the failure type
      was categorized as either adhesive (failure at adhesive layer), cohesive (failure
      at ceramic or composite resin), or mixed (failure between adhesive layer and
      substrate). Two-way ANOVA and the Tukey's HSD post-hoc test were applied to test
      for significant differences in bond strength values in relation to different
      materials and surface pretreatment (p < 0.05). RESULTS: The highest microtensile
      repair bond strength for Vita Suprinity was reported in group CO (33.1 +/- 2.4
      MPa) and the lowest in group HF (27.4 +/- 4.4 MPa). Regarding IPS e.max CAD,
      group CO showed the highest (30.5 +/- 4.9 MPa) and HF the lowest microtensile
      bond strength (22.4 +/- 5.7 MPa). Groups HF, HF-H, and CO showed statistically
      significant differences in terms of all ceramic types used (p < 0.05). The
      control group showed exclusively adhesive failures, while in HF, HF-H, and CO
      groups, mixed failures were predominant. CONCLUSIONS: Repair bond strength to
      zirconia-reinforced lithium silicate ceramics and lithium-disilicate glass
      ceramic could be improved when ceramic surfaces are sandblasted with CoJet sand
      followed by silanization.

PMID- 27042709
TI  - Understanding the hydrogen bonds in ionic liquids and their roles in properties
      and reactions.
AB  - Ionic liquids (ILs) have many potential applications in the chemical industry. In
      order to understand ILs, their molecular details have been extensively
      investigated. Intuitively, electrostatic forces are solely important in ILs.
      However, experiments and calculations have provided strong evidence for the
      existence of H-bonds in ILs and their roles in the properties and applications of
      ILs. As a structure-directing force, H-bonds are responsible for ionic pairing,
      stacking and self-assembling. Their geometric structure, interaction energy and
      electronic configuration in the ion-pairs of imidazolium-based ILs and protic
      ionic liquids (PILs) show a great number of differences compared to conventional
      H-bonds. In particular, their cooperation with electrostatic, dispersion and pi
      interactions embodies the physical nature of H-bonds in ILs, which anomalously
      influences their properties, leading to a decrease in their melting points and
      viscosities and thus fluidizing them. Using ILs as catalysts and solvents, many
      reactions can be activated by the presence of H-bonds, which reduce the reaction
      barriers and stabilize the transition states. In the dissolution of
      lignocellulosic biomass by ILs, H-bonds exhibit a most important role in
      disrupting the H-bonding network of cellulose and controlling microscopic
      ordering into domains. In this article, a critical review is presented regarding
      the structural features of H-bonds in ILs and PILs, the correlation between H
      bonds and the properties of ILs, and the roles of H-bonds in typical reactions. 

PMID- 27042710
TI  - Destructive interactions of dirhodium(II) tetraacetate with beta metallothionein
      rh1a.
AB  - Metal-based therapeutics are vital tools in medicine. Metal-chelating proteins
      can dramatically decrease drug efficacy. Dirhodium(II) tetraacetate, a potential
      anticancer compound, binds in vitro to 8 cysteines of the human metallothionein
      1a beta-fragment. Electrospray ionization mass spectrometry shows that the final
      product is the Rh2(4+) core encapsulated by the beta fragment of the
      metallothionein protein protein.

PMID- 27042711
TI  - Corrigendum.

PMID- 27042712
TI  - [Early childhood caries and caries experience in permanent dentition: A 15-year
      cohort study].

PMID- 27042714
TI  - Response to the Letter to the Editor.

PMID- 27042713
TI  - Mechanical effects of different Swiss market-leading dentifrices on dentin.

PMID- 27042716
TI  - METHODOLOGICAL RICHES IN 2015.

PMID- 27042715
TI  - [Jaw orthodontics].

PMID- 27042717
TI  - [Muscle-skeletal pain].
AB  - The paper is devoted to the most complicated aspects of low back pain. The
      differences between specific and nonspecific low back pain using the "red flags"
      system is highlighted. The authors consider the causes of pain chronification
      (the "yellow flags" system) and the necessity of using a biopsychosocial model.
      Main pathogenetic mechanisms of chronic muscle/skeletal pain are considered and
      the possible involvement of several mechanism in the pathogenesis of chronic pain
      as well as the use of complex therapy is discussed. The high efficacy and safety
      of ketorolac in treatment of nonspecific muscle/skeletal pain is demonstrated.

PMID- 27042718
TI  - [Anxiety and fear in children and adolescents].
AB  - The article presents an overview of scientific publication devoted to the study
      of epidemiology, etiology, pathogenesis, clinical manifestation and basic
      approaches to treatment of anxious-phobic disorders in children.

PMID- 27042719
TI  - Professor Sir Salvador Moncada MD PhD FRS.

PMID- 27042720
TI  - Should we screen cardiovascular patients   for thyroid dysfunction?

PMID- 27042721
TI  - Adrenal hormones and the heart.

PMID- 27042722
TI  - Fight inertia!

PMID- 27042723
TI  - COMMON STEM--navir.

PMID- 27042724
TI  - Denosumab (Prolia) and male osteoporosis. Do not use in men (or in women).
AB  - No proven efficacy in preventing osteoporotic fractures in men, but serious
      adverse effects including atypical fractures and symptomatic hypocalcaemia.

PMID- 27042725
TI  - Sorafenib (NEXAVAR) and differentiated thyroid cancer. Toxic, and no proof of
      improved survival.
AB  - Radiological progression was delayed by 5 months in one trial, but its design
      does not allow reliable analysis of survival. Numerous, sometimes serious,
      adverse effects occurred.

PMID- 27042726
TI  - Pasireotide (SIGNIFOR) in acromegaly. After treatment failure: better than
      pegvisomant.
AB  - In a trial including 198 patients in whom several lines of treatments had failed,
      pasireotide normalised IGF-1 and GH levels and sometimes reduced the size of the
      pituitary adenoma, but often at a cost of developing diabetes.

PMID- 27042727
TI  - Paracetamol + opium (Izalgi) higher-dose for oral administration. A poor choice
      for analgesia.

PMID- 27042728
TI  - Insulin lispro (HUMALOG KWIKPEN) double concentration (200 units/ml). Risk of
      confusion.

PMID- 27042729
TI  - Thiocolchicoside: review of adverse effects.
AB  - Thiocolchicoside has long been used as a muscle relaxant, despite a lack of
      proven efficacy beyond the placebo effect. Its chemical structure consists of
      colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its
      adverse effects are therefore likely to be similar to those of colchicine. Using
      the standard Prescrire methodology, we reviewed the available data on the adverse
      effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell
      disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders
      have all been recorded in the French and European pharmacovigilance databases and
      in the periodic updates that the companies concerned submit to regulatory
      agencies. These data do not specify the frequency of the disorders nor do they
      identify the most susceptible patient populations. Thiocolchicoside is
      teratogenic in experimental animals and also damages chromosomes. Human data are
      limited to a follow-up of about 30 pregnant women (no major malformations) and
      reports of altered spermatogenesis, including cases of azoospermia. In practice,
      there is no justification for exposing patients to the adverse effects of
      thiocolchicoside. It is better to use an effective, well-known analgesic for
      patients complaining of muscle pain, starting with paracetamol.

PMID- 27042730
TI  - Bismuth: more cases of encephalopathy.

PMID- 27042731
TI  - Thiocolchicoside: close related to colchicine.

PMID- 27042732
TI  - "Weak" opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky
      than morphine.
AB  - So-called weak opioid analgesics are often used to treat severe pain, or when
      paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) proves inadequate.
      But are weak opioids any more effective than paracetamol or NSAIDs on nociceptive
      pain, and are they better tolerated than morphine? To answer these questions, we
      conducted a review of literature using the standard Prescrire methodology. The
      potency of codeine and tramadol is strongly influenced by the cytochrome P450
      isoenzyme CYP2D6 genotype, which varies widely from one person to another. This
      explains reports of overdosing or underdosing after administration of standard
      doses of the two drugs. The potency of morphine and that of buprenorphine, an
      opioid receptor agonist-antagonist, appears to be independent of CYP2D6 activity.
      All "weak" opioids can have the same dose-dependent adverse effects as morphine.
      There is no evidence that, at equivalent analgesic efficacy, weak opioids carry a
      lower risk of addiction than low-dose morphine. Respiratory depression can occur
      in ultrarapid metabolisers after brief exposure to standard doses of codeine or
      tramadol. Similar cases have been reported with dihydrocodeine in patients with
      renal failure. In addition, tramadol can cause a serotonin syndrome,
      hypoglycaemia, hyponatraemia and seizures. Several trials have compared different
      weak opioids in patients with post-operative pain. A single dose of a weak
      opioid, possibly combined with paracetamol, has greater analgesic efficacy than
      paracetamol alone but is not more effective than an NSAID alone. There is a
      dearth of evidence on weak opioids in patients with chronic pain. Available
      trials fail to show that a weak opioid has markedly superior analgesic efficacy
      to paracetamol or an NSAID. Sublingual buprenorphine at analgesic doses appears
      less likely to cause respiratory depression, but it seems to have weak analgesic
      efficacy. In practice, when opioid therapy is needed, there is no evidence that
      codeine, dihydrocodeine or tramadol is less risky than morphine at its lowest
      effective dose. Compared to morphine, the efficacy of these drugs varies more
      from one patient to another, and their multiple pharmacokinetic interactions can
      be difficult to manage. There is also a sometimes unpredictable risk of serious
      over-dose. Tramadol has additional adverse effects unrelated to its opioid
      effects. Weak opioids require at least as much vigilance as morphine, despite the
      major differences in their reputation and regulation.

PMID- 27042733
TI  - Complex analgesic actions of opioids.

PMID- 27042734
TI  - Pregnancy: morphine, or sometimes buprenorphine, when paracetamol is ineffective.

PMID- 27042735
TI  - Influenza vaccination during pregnancy.
AB  - In a randomised, double-blind trial in pregnant women, a seasonal inactivated
      influenza vaccine without a lipid adjuvant and covering strain A/H1N1v was
      partially effective: the incidence of influenza in the mothers and their infants
      was about 1.8% with the vaccine versus 3.6% with placebo. No noteworthy adverse
      reactions were reported.

PMID- 27042736
TI  - Oseltamivir and influenza: still no robust data.

PMID- 27042737
TI  - Oseltamivir: over 15 years of data retention and systematic stonewalling.

PMID- 27042738
TI  - Enrolled nurses take on new roles.

PMID- 27042739
TI  - Seeking more recognition for Te Runanga Tauira.

PMID- 27042740
TI  - PREVENTION AND MANAGEMENT OF INSULIN-ASSOCIATED HYPOGLYCEMIA IN HOSPITALIZED
      PATIENTS.
AB  - OBJECTIVE: To determine whether appropriate therapeutic changes in insulin doses
      are made to prevent and manage insulin-associated hypoglycemic events in non
      critically ill hospitalized patients. METHODS: This retrospective study was
      conducted in hospitalized adults on medical or surgical floors with insulin
      associated hypoglycemia, excluding treatment with insulin infusions, insulin
      pumps, and parenteral nutrition. The first hypoglycemic event after 48 hours of
      admission was the index event. Over the 1-year study period, a total of 457
      insulin-associated hypoglycemic events were included as index events. RESULTS: An
      indication for an insulin dose adjustment was identified in 32 and 42% of
      patients on day -2 and day -1, respectively, before the index hypoglycemic event,
      of which 35 and 55%, respectively, had an insulin dose reduction >=10%. Following
      the hypoglycemic event, 44% of patients had an insulin dose reduction of >=20%.
      Therapeutic reduction of the total daily insulin dose by >=20% was associated
      with increased odds of normoglycemia and lower odds of hyperglycemia but was not
      associated with lower odds of recurrent hypoglycemia on the day following the
      index hypoglycemic event. There was a high prevalence of hypoglycemic risk
      factors in this population, with kidney disease and nil per os status being the
      most prevalent contributing factors. CONCLUSION: Adherence to the current
      practice recommendation to reduce insulin doses in patients with borderline
      hypoglycemia and following overt hypoglycemia was modest. Further studies are
      needed to understand the associated risks and to define appropriate therapeutic
      changes for insulin treated patients with borderline and overt hypoglycemia.
      ABBREVIATIONS: AKI = acute kidney injury BG = blood glucose CKD = chronic kidney
      disease ESRD = end-stage renal disease ICU = intensive care unit NPH = Neutral
      Protamine Hagedorn NPO = nil per os OR = odds ratio TDD = total daily dose.

PMID- 27042741
TI  - ADULT HYPOPHOSPHATASIA TREATED WITH TERIPARATIDE: REPORT OF 2 PATIENTS AND REVIEW
      OF THE LITERATURE.
AB  - OBJECTIVE: Hypophosphatasia (HPP) is a rare inherited metabolic bone disease from
      deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase
      (TNSALP). Reportedly, teriparatide (parathyroid hormone 1-34) can benefit the
      adult form of HPP, including fracture healing. We studied 2 women with adult HPP
      given teriparatide and reviewed the reports of 6 additional patients. METHODS: A
      68-year-old black woman (patient 1) described low-trauma fractures and had
      subnormal serum alkaline phosphatase (ALP) activity. Biochemical findings were
      consistent with HPP. Mutation analysis revealed a heterozygous defect in exon 10
      of TNSALP (ALPL). Teriparatide was injected daily for 2 years. Four years later,
      she fractured her right hip. Treatment was resumed for 8 months without further
      fractures. A 53-year-old white woman (patient 2) reported low-trauma fractures
      and had subnormal serum ALP. Mutation analysis revealed a heterozygous defect in
      exon 8 of TNSALP. She injected teriparatide daily for 2 years. One year later,
      bone mineral density (BMD) declined and treatment was resumed for 3 months. When
      she sustained a sacral fracture, teriparatide was administered for a further 18
      months. RESULTS: Patient 1's serum ALP increased while receiving teriparatide and
      returned to baseline after its discontinuation. BMD remained unchanged, but no
      fractures were sustained. Patient 2's serum ALP increased, but the improvement
      was not sustained. Femoral neck BMD increased significantly during the first
      cycle, declined significantly afterwards, and was regained during a second course
      of teriparatide. CONCLUSION: Teriparatide shows some benefit for adult HPP.
      ABBREVIATIONS: ALP = alkaline phosphatase BMD = bone mineral density BSAP = bone
      specific alkaline phosphatase CTX = C-telopeptide DXA = dual-energy X-ray
      absorptiometry FN = femoral neck HPP = hypophosphatasia LS = lumbar spine PEA =
      phosphoethanolamine PLP = pyridoxal 5'-phosphate PTH = parathyroid hormone SQ =
      subcutaneous TNSALP = tissue-nonspecific isoenzyme of alkaline phosphatase TPTD =
      teriparatide.

PMID- 27042742
TI  - EVIDENCE-BASED CURRICULAR CONTENT IMPROVES STUDENT KNOWLEDGE AND CHANGES
      ATTITUDES TOWARDS TRANSGENDER MEDICINE.
AB  - OBJECTIVE: Previous studies have demonstrated that the addition of transgender
      medicine content to a medical school curriculum increased students' comfort and
      willingness to treat transgender patients. We aimed to demonstrate that (1)
      evidence-based curricular content would improve knowledge of and change attitudes
      towards transgender medicine, and (2) students would consider cross-sex hormone
      therapy a legitimate treatment option for transgender patients. METHODS:
      Curricular content with a focus on the biologic evidence for the durability of
      gender identity was added to the first-year medical program at Boston University
      School of Medicine. Immediately before and after exposure to the content,
      students were presented with an assessment of their knowledge of the etiology of
      gender identity. RESULTS: Immediately following exposure to the content, a
      significant number of students changed their answer regarding the etiology of
      gender identity so that the number of correct responses increased from 63% (n =
      56) to 93% (n = 121) (P<.001). For transgender treatment, the number of correct
      responses increased from 20% (n = 56) before exposure to the content to 50% (n =
      121) following exposure (P<.001). CONCLUSION: The addition of transgender
      medicine content to a medical school curriculum with a focus on the biologic
      evidence for a durable gender identity is an effective means of educating
      students about the etiology of gender identity and the appropriateness of cross
      sex hormone therapy as a treatment for transgender patients.

PMID- 27042743
TI  - MANAGEMENT OF TYPE 2 DIABETES: ARE WE MAKING PROGRESS?
AB  - ABBREVIATIONS: HbA1c = glycated hemoglobin.

PMID- 27042744
TI  - KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR GENES AND THEIR HLA-C LIGANDS IN
      HASHIMOTO THYROIDITIS IN A CHINESE POPULATION.
AB  - OBJECTIVE: Natural killer (NK) cells serve as primary immune surveillance and are
      partially regulated by combinations of killer immunoglobulin-like receptors (KIR)
      and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell
      activity have been associated with Hashimoto thyroiditis (HT). The aim of this
      study was to determine whether certain KIR/HLA-C genotype combinations play a
      role in HT pathogenesis. METHODS: The present study enrolled 107 unrelated HT
      patients and 108 random healthy individuals in a case-control study. Blood was
      collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed
      by polymerase chain reaction with sequence specific primers (PCR-SSP), followed
      by electrophoresis on agarose gels. RESULTS: Among a panel of KIR2D/HLA-C
      genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly
      increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To
      further analyze the precise genotype, we investigated inhibitory or activating
      KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes
      were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+)
      was significantly decreased in HT patients compared to controls (48.60% vs.
      70.37%, P = .001). CONCLUSION: Our data suggest that KIR2DS2/HLA-C1 may correlate
      with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in
      the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis.
      In conclusion, our findings may further elucidate the mechanisms underlying the
      pathogenesis of HT and other autoimmune diseases. ABBREVIATIONS: HLA-C = human
      leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like
      receptor NK = natural killer PCR = polymerase chain reaction.

PMID- 27042745
TI  - ASSOCIATION BETWEEN 25-HYDROXYVITAMIN D AND INTACT PARATHYROID HORMONE LEVELS
      ACROSS LATITUDE AMONG ADULTS WITH AFRICAN ANCESTRY.
AB  - OBJECTIVE: To compare levels of 25-hydroxyvitamin D (25[OH]D) associated with a
      plateauing of intact parathyroid (iPTH) across latitudes among adults with
      African ancestry. METHODS: This study included approximately 500 adults of
      African ancestry ages 25 to 45 years living in 4 sites: Chicago, Illinois (41
      degrees N), Jamaica (17 degrees N), Ghana (6 degrees N), and South Africa (34
      degrees S). Multivariate linear regression models, a nonlinear logistic growth
      curve model, and piecewise linear models with a single knot were fitted to
      estimate the 25[OH]D level associated with a plateauing of iPTH with adjustment
      for covariates. Goodness of fit was compared using computer intensive permutation
      tests. RESULTS: Mean age was 34.7 (SD 6.2) years, and 46.5% were male. Within
      each site, the percentage of participants with an iPTH level >=65 pg/mL was
      higher among females versus males and was most frequent among South African
      females (17.1%) and lowest among Jamaican males (0.6%). Goodness of fit tests
      supported linear regression as the preferred model for the association between
      iPTH and 25[OH]D in the 4 sites with no 25[OH]D level associated with iPTH
      plateauing in any site. The slope of the association between 25[OH]D and iPTH
      differed by latitude; it was strongest in the U.S. (beta = -0.81; 95% confidence
      interval [CI] = -1.03, -0.59), and weakest in Jamaica (beta = -0.45; 95% CI 
      0.71, -0.18) with covariate adjustment, but differences in slopes were small.
      CONCLUSION: The association between 25[OH]D and iPTH appears linear among adults
      with African ancestry regardless of latitude within a range of 25[OH]D levels
      between 10 and 60 ng/mL. ABBREVIATIONS: BMI = body mass index CI = confidence
      interval eGFR = estimated glomerular filtration rate iPTH = intact parathryoid
      hormone 25[OH]D = 25-hydroxyvitamin D.

PMID- 27042746
TI  - TRENDS IN THE CARE AND OUTCOMES OF MEDICARE BENEFICIARIES WITH TYPE 2 DIABETES,
      2002-2011.
AB  - OBJECTIVE: To summarize characteristics of Medicare beneficiaries with type 2
      diabetes and to describe changing trends in care and outcomes. METHODS: We
      conducted a retrospective cohort study of a nationally representative 5% sample
      of fee-for-service Medicare beneficiaries 65 years and older with prevalent type
      2 diabetes, between January 1, 2002, and December 31, 2011. The main outcome
      measures were diabetes-related screening tests, mortality, hospital admissions,
      dialysis, and lower extremity amputation. RESULTS: The average age of Medicare
      beneficiaries with diabetes was 76.5 years, 56% were women, and 83% were white.
      Screening practices in beneficiaries with diabetes improved from 2002 to 2011,
      with rising rates of foot exams, renal screening, hemoglobin A1c tests, and lipid
      profile tests. The prevalence of nephropathy and neuropathy increased. Although
      inpatient admissions declined from 2002 to 2011, diabetes-related emergency
      department visits increased. Amputation and end-stage renal disease remained
      static, while 1-year mortality declined over the study period. CONCLUSION: In
      this medically complex group of patients with high comorbidity, we observed
      improvements in screening practices and room for further improvement. Although
      the mortality rate decreased, other outcomes did not improve consistently. Health
      care resource has changed over time, with decreased hospital admissions and
      increased emergency department visits. ABBREVIATIONS: CCW = Chronic Conditions
      Data Warehouse ESRD = end-stage renal disease HbA1c = hemoglobin A1c HEDIS =
      Healthcare Effectiveness Data and Information Set ICD-9-CM = International
      Classification of Diseases, Ninth Revision, Clinical Modification.

PMID- 27042747
TI  - SHOULD FNA BE PERFORMED IN PATIENTS WITH A MULTINODULAR GOITER AND COMPRESSIVE
      SYMPTOMS?
AB  - OBJECTIVE: In this study, we aimed to determine whether preoperative thyroid fine
      needle aspiration (FNA) in patients with multinodular goiter (MNG) and
      compressive symptoms influences the type of thyroid surgery performed, the
      incidence of recurrent thyroid cancer, or the need for successive surgery.
      METHODS: We retrospectively reviewed the charts of 431 patients who underwent
      thyroidectomy at our institution from 2008 to 2011. Patients who presented with
      compressive symptoms and no prior FNA at initial presentation were included in
      this study. RESULTS: Eighty patients met the criteria for our study, of which 46
      (57.5%) underwent FNA prior to surgery and 34 (42.5%) were referred to surgery
      without FNA. The prevalence rates of malignancy (>1 cm) on surgical pathology in
      the FNA and non-FNA groups were 41% (n = 19) and 38% (n = 13), respectively.
      There was no statistically significant difference between the rate of
      total/subtotal thyroidectomies (71.7% in FNA vs. 79.4% in non-FNA, P = .31),
      lobectomies/partial thyroidectomies (28.3% in FNA vs. 20.5% in non-FNA, P = .43),
      neck lymph node dissections (P = .89) or subsequent surgeries (P = .72) between
      the 2 groups. CONCLUSION: Our findings show that preoperative FNA in patients
      with an MNG and compressive symptoms does not influence the type of surgery
      performed, short-term outcomes, or the need for subsequent surgeries. Further
      studies are needed to validate the need for preoperative FNA in such patients.
      ABBREVIATIONS: FNA = fine-needle aspiration MNG = multinodular goiter WHO = World
      Health Organization.

PMID- 27042748
TI  - VISUAL VIGNETTE.

PMID- 27042749
TI  - SERIAL CHANGES OF LIVER FUNCTION TESTS BEFORE AND DURING METHIMAZOLE TREATMENT IN
      THYROTOXIC PATIENTS.
AB  - OBJECTIVE: Overt hyperthyroidism and methimazole (MMI) treatment are frequently
      associated with abnormal liver function tests (LFTs). We describe the serial
      changes of LFTs in MMI-treated hyperthyroid patients. METHODS: We retrospectively
      analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism
      (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone
      induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to
      60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone,
      free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase
      (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI
      treatment. The concomitant medication was stable during MMI treatment. RESULTS:
      At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST
      levels >2* the upper limit of normal (ULN). In most patients with baseline
      abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST.
      Thirteen patients with normal baseline LFT had <2* the ULN elevations of LFT
      sometime during treatment. There was a case of significant hepatotoxicity. During
      treatment, there were no significant differences in LFT levels between patients
      with initially normal or abnormal LFT. In a Cox proportional hazard regression
      model, abnormal LFT at baseline, abnormal thyroid function at the last
      evaluation, and MMI dose were not predictors of abnormal LFT at the final
      evaluation. CONCLUSION: MMI treatment can induce insignificant LFT elevation, <2*
      the ULN. MMI can be safely administered in hyperthyroid patients with abnormal
      LFT, and normalization of increased AST and ALT levels should be anticipated.
      ABBREVIATIONS: ALT = alanine aminotransferase AST = aspartate aminotransferase
      fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF =
      last observation carried forward MMI = methimazole PTU = propylthiouracil TSH =
      thyroid-stimulating hormone ULN = upper limit of normal.

PMID- 27042750
TI  - TRABECULAR BONE SCORE CHANGE DIFFERS WITH REGARD TO 25(OH)D LEVELS IN PATIENTS
      TREATED FOR ADULT-ONSET GROWTH HORMONE DEFICIENCY.
AB  - OBJECTIVE: Vitamin D is important in bone health. However, potential
      relationships of concomitant vitamin D deficiency with growth hormone deficiency
      (GHD) and the possibility that vitamin D inadequacy may alter the skeletal
      effects of growth hormone (GH) replacement therapy have not been adequately
      evaluated. METHODS: A prospective study was conducted in adult-onset GHD patients
      treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score
      (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25
      hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The
      study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff
      defined as the 50(th) percentile at each follow-up time point. RESULTS: Fifty
      seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24
      months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5%
      (both P<.05), with no difference according to 25(OH)D levels. TBS increased
      (+1.39 +/- 3.6%) in those whose 25(OH)D was above the 50(th) percentile but
      decreased (-1.36 +/- 5.6%, P<.05) in the cohort below the 50(th) percentile of
      25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and
      25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25,
      P<.05). CONCLUSION: A differential effect of GH on TBS change was observed; TBS
      increased only in the cohort with 25(OH)D above the 50(th) percentile. Vitamin D
      sufficiency may be required to obtain optimal effects of GH treatment on bone
      quality, as assessed by TBS, in GHD adults. ABBREVIATIONS: AO-GHD = adult-onset
      GHD BMD = bone mineral density BMI = body mass index Ca = calcium CTx =
      carboxyterminal collagen crosslinks CV = coefficient of variation DXA = dual
      energy X-ray absorptiometry ECLIA = enzyme-labeled chemiluminescent immunometric
      assay GH = growth hormone GHD = growth hormone deficiency IGF-1 = insulin-like
      growth factor 1 LS BMD = lumbar spine BMD OC = osteocalcin 25(OH)D = 25
      hydroxyvitamin D P = phosphorus PTH = parathyroid hormone rhGH = recombinant
      human GH TBS = trabecular bone score TH BMD = total hip BMD.

PMID- 27042751
TI  - Epigallocatechin Gallate Remodels Fibrils of Lattice Corneal Dystrophy Protein,
      Facilitating Proteolytic Degradation and Preventing Formation of Membrane
      Permeabilizing Species.
AB  - Lattice corneal dystrophy is associated with painful recurrent corneal erosions
      and amyloid corneal opacities induced by transforming growth factor beta-induced
      protein (TGFBIp) that impairs vision. The exact mechanism of amyloid fibril
      formation in corneal dystrophy is unknown but has been associated with
      destabilizing mutations in the fourth fasciclin 1 (Fas1-4) domain of TGFBIp. The
      green tea compound epigallocatechin gallate (EGCG) has been found to inhibit
      fibril formation of various amyloidogenic proteins in vitro. In this study, we
      investigated the effect of EGCG as a potential treatment in lattice corneal
      dystrophy (LCD) using Fas1-4 with the naturally occurring LCD-inducing A546T
      mutation. A fewfold molar excess of EGCG was found to inhibit fibril formation in
      vitro by directing Fas1-4 A546T into stable EGCG-bound protein oligomers.
      Incubation with 2 molar equiv of EGCG led to a 4-fold reduction in the
      aggregates' membrane disruptive potential, potentially indicative of
      significantly lower cytotoxicity with regard to corneal erosions. EGCG did not
      induce oligomer formation by wild-type Fas1-4, indicating that treatment with
      EGCG would not interfere with the native function of the wild-type protein.
      Addition of EGCG to 10-day-old fibrils reduced fibril content in a dose-dependent
      manner. Proteinase K was found to reduce the light scattering of nontreated
      fibrils by 31% but reduced that of fibrils treated with 8 molar equiv of EGCG by
      85%. This suggests that EGCG remodeling of fibril structure can facilitate
      aggregate removal by endogenous proteases and thus alleviate the protein
      deposits' light scattering symptoms.

PMID- 27042752
TI  - Ovarian Cancer, the Revised FIGO Staging System, and the Role of Imaging.
AB  - OBJECTIVE: It is now recognized that ovarian cancer includes a heterogeneous
      group of malignant epithelial tumors originating from the ovaries, fallopian
      tubes, or peritoneum. This development has prompted the International Federation
      of Gynecology and Obstetrics (FIGO) to issue a revised staging system that can
      provide prognostic information and guidance on personalized management of ovarian
      cancer. CONCLUSION: We review the epidemiology of ovarian cancer, the new FIGO
      staging system, and the role of imaging in the assessment, staging, and follow-up
      of ovarian cancer.

PMID- 27042753
TI  - Reviewing hybrid coronary revascularization: challenges, controversies and
      opportunities.
AB  - Two main approaches to myocardial revascularization currently exist, coronary
      artery bypass and percutaneous coronary intervention. In patients with advanced
      coronary artery disease, coronary artery bypass surgery is associated with
      improved long term outcomes while percutaneous coronary intervention is
      associated with lower periprocedural complications. A new approach has emerged in
      the last decade that attempts to reap the benefits of bypass surgery and stenting
      while minimizing the shortcomings of each approach. This new approach, hybrid
      coronary revascularization, has shown encouraging early results. Minimally
      invasive techniques for bypass surgery have played a large part of bringing this
      approach into contemporary practice. 

PMID- 27042754
TI  - Efficient Microwave-Assisted Functionalization of the Aurivillius-Phase
      Bi2SrTa2O9.
AB  - A new method of acidification and subsequent functionalization of the Aurivillius
      phase Bi2SrTa2O9 (BST), using microwave irradiation, was developed. This method
      enables to obtain hybridized phases from layered BST. Functionalization of BST by
      various kinds of amines and diamines can be achieved in a few hours only,
      compared to much longer time (over a week) using conventional heating. Good
      crystallinity of the compounds is kept. In addition, a microwave-assisted
      preintercalation strategy was developed, allowing inserting new amines (bearing
      cyclic or aromatic groups) between the oxide layers previously unseen in this
      type of compound. This work opens new perspectives for the fast and easy
      functionalization of layered oxides with more elaborated molecules. 

PMID- 27042755
TI  - Photochemical Microscale Electrophoresis Allows Fast Quantification of
      Biomolecule Binding.
AB  - Intricate spatiotemporal patterns emerge when chemical reactions couple to
      physical transport. We induce electrophoretic transport by a confined
      photochemical reaction and use it to infer the binding strength of a second,
      biomolecular binding reaction under physiological conditions. To this end, we use
      the photoactive compound 2-nitrobenzaldehyde, which releases a proton upon 375 nm
      irradiation. The charged photoproducts locally perturb electroneutrality due to
      differential diffusion, giving rise to an electric potential Phi in the 100 MUV
      range on the micrometer scale. Electrophoresis of biomolecules in this field is
      counterbalanced by back-diffusion within seconds. The biomolecule concentration
      is measured by fluorescence and settles proportionally to exp(-MU/D Phi).
      Typically, binding alters either the diffusion coefficient D or the
      electrophoretic mobility MU. Hence, the local biomolecule fluorescence directly
      reflects the binding state. A fit to the law of mass action reveals the
      dissociation constant of the binding reaction. We apply this approach to quantify
      the binding of the aptamer TBA15 to its protein target human-alpha-thrombin and
      to probe the hybridization of DNA. Dissociation constants in the nanomolar regime
      were determined and match both results in literature and in control experiments
      using microscale thermophoresis. As our approach is all-optical, isothermal and
      requires only nanoliter volumes at nanomolar concentrations, it will allow for
      the fast screening of biomolecule binding in low volume multiwell formats.

PMID- 27042756
TI  - Successful Conservative Management of a Retroperitoneal Abscess with a Sinus to
      the Colon: A Case Report.
AB  - A sinus between the colon and a retroperitoneal abscess is a rare entity that
      usually occurs as a complication of a primary condition such as Crohn's disease,
      radiation enteritis, or diverticular disease. Herein, we report a 72-year-old
      woman with a retroperitoneal abscess and a sinus formation between the abscess
      and the colon after an iatrogenic injury to her left colon. The retroperitoneal
      abscess was detected 1 week after the patient had undergone a left
      nephroureterectomy for recurrent ureteral cancer. The patient's general
      performance status allowed conservative management with antibiotics and
      percutaneous drainage. The abscess resolved, and the sinus closed after 3 weeks
      of treatment. In the absence of surgical pathology in the colon, and if the
      patient's general condition is good enough to tolerate conservative management,
      treatment using antibiotics plus percutaneous drainage is effective for cases of
      retroperitoneal abscess with a sinus between the colon and abscess.

PMID- 27042757
TI  - "Hedge Your Bets": Technology's Role in Young Gay Men's Relationship Challenges.
AB  - Technology is playing an increasingly pervasive role among young gay men in the
      process of meeting potential romantic or sexual partners. We investigated
      challenges posed by technology related to young gay men's relationships. Focus
      groups (n = 9) of young gay men aged 18-24 (n = 43) were transcribed verbatim,
      and thematic analysis was used to identify two major themes regarding challenges
      to relationship development and maintenance. Subthemes include unrealistic
      expectations of relationships, inauthentic self-presentation online, sexual
      primacy over romance, increased opportunities for infidelity, and jealousy. The
      implications of this study for sexual education and sexual health promotion are
      discussed.

PMID- 27042758
TI  - Bronchodilator responsiveness in wheezy infants predicts continued early
      childhood respiratory morbidity.
AB  - OBJECTIVE: Spirometry including bronchodilator responsiveness is considered
      routine in the workup of asthma in older children. However, in wheezy infants the
      existence of bronchodilator responsiveness and its prognostic significance remain
      unclear. METHODS: Infants (< 2 years) with chronic or recurrent wheezing or
      coughing were evaluated by infant pulmonary function testing (PFT). Maximal
      expiratory flow at the point of functional residual capacity (VmaxFRC) was
      measured before and 20 minutes after salbutamol administration. Only infants with
      an obstructive profile (VmaxFRC < 80% predicted) were included. The infants were
      divided into two groups with regard to whether or not a response to salbutamol
      was observed on PFT. A response was defined as a mean VmaxFRC after salbutamol
      administration exceeding the upper confidence interval limit of individual pre
      bronchodilator VmaxFRC measurements. Follow-up data was gathered after a mean of
      2 years. MEASUREMENTS AND MAIN RESULTS: Sixty infants were included in the study
      of which 32 (53%) demonstrated responsiveness to bronchodilators. The infants in
      the responsive group had a significantly higher frequency of physician visits for
      wheezing than the non-responders (3.0 mean visits/yr vs. 1.5 respectively, P =
      0.03), and had a higher likelihood of having received asthma medication in the
      last year of the follow-up period (84% vs. 50% respectively, RR: 1.68[1.10
      2.56]). At the end of the follow-up period, more parents in the responsive group
      reported continued respiratory disease (71% vs. 22%, RR:3.21[1.30-7.95]).
      CONCLUSIONS: Bronchodilator responsiveness can be demonstrated by infant PFT in
      infants with recurrent wheezing and can predict increased respiratory morbidity
      until 3 years of age.

PMID- 27042759
TI  - Synthesis of Water-Soluble, Thiolate-Protected Gold Nanoparticles Uniform in
      Size.
AB  - By a modification of the method of Brust et al., water-soluble, thiolate
      protected gold nanoparticles that are uniform in size were synthesized with no
      requirement for purification. The modification of the method was equilibration in
      the first step, which proved crucial for achieving size homogeneity. The thiol-to
      gold ratio controlled the size of the particles, and the choice of thiol
      controlled the reactivity of the particles toward thiol exchange.

PMID- 27042760
TI  - Important Mutations Contributing to High-Level Penicillin Resistance in Taiwan19F
      14, Taiwan23F-15, and Spain23F-1 of Streptococcus pneumoniae Isolated from
      Taiwan.
AB  - Penicillin-resistant Streptococcus pneumoniae is a serious concern worldwide. In
      this study, we analyzed the cause of beta-lactam resistance in pandemic multidrug
      resistant clones. A total of 41 penicillin-nonsusceptible clinical isolates were
      collected from 1996 to 2012. Sero- and molecular typing confirmed that these
      isolates were clonal types of Taiwan19F-14, Taiwan23F-15, and Spain23F-1. Sero
      switching was found in four isolates. All isolates were multidrug resistant.
      Sequencing analysis of the penicillin binding proteins (PBPs) was performed on
      PBP1a, 2b, and 2x, and a large number of mutations were identified in comparing
      to clinical penicillin-susceptible isolates and the recipient strain R6 used for
      homologous recombination. The T451A substitution was the key amino acid in PBP2b
      that contributed to penicillin resistance. T338A in PBP2x played a role in
      resistance and reached the highest level of resistance when combined with other
      mutations in PBP2x. High-level penicillin resistance could not be obtained
      without the combination of mutations in PBP1a with PBP2b and 2x. The amino acid
      substitutions in PBP1a, 2b, and 2x were the crucial factors for beta-lactam
      resistance.

PMID- 27042762
TI  - Ceftazidime-avibactam (CTZ-AVI) as a treatment for hospitalized adult patients
      with complicated intra-abdominal infections.
AB  - Avibactam, a novel beta-lactamase inhibitor, has recently been co-formulated with
      ceftazidime and approved for use in patients with complicated intra-abdominal and
      urinary tract infections, where no better treatment alternative exists. The basis
      for its FDA approval has been the extensive clinical experience with ceftazidime
      and the demonstration in vitro and in animal models that the addition of
      avibactam reverses resistance to ceftazidime in extended-spectrum beta-lactamase
      and some carbapenemase-producing Enterobacteriaceae. Early clinical data are
      promising, with efficacy demonstrated in patients with complicated intra
      abdominal and urinary tract infections. This review will summarize the in vitro,
      animal and clinical data available on this agent to date. 

PMID- 27042761
TI  - A higher aspect ratio enhanced bioaccumulation and altered immune responses due
      to intravenously-injected aluminum oxide nanoparticles.
AB  - Aluminum oxide nanoparticles (AlO NP) have been widely utilized in a variety of
      areas, including in the optical, biomedical and electronic fields and in the
      overall development of nanotechnologies. However, their toxicological profiles
      are still not fully developed. This study compared the distribution and
      immunotoxicity of two rod-types of AlO NP. As reported previously, the two types
      of AlO NP had different aspect ratios (long-type: 6.2 +/- 0.6, short-type: 2.1 +/
      0.4), but the size and surface charge were very similar. On Day 14 after a
      single intravenous (IV) injection (1.25 or 5 mg/kg), both AlO NP accumulated
      primarily in the liver and spleen and altered the levels of redox response
      related elements. The accumulated level was higher in mice exposed to the long
      type AlO NP compared to the short-type. Additionally, it was noted that the
      levels of IL-1beta, IL-8 and MCP-1 were enhanced in the blood of mice exposed to
      both types of AlO NP and the percentages of neutrophils and monocytes among all
      white blood cells were increased only in mice injected with the long-type AlO NP
      (5 mg/kg). In addition, as compared to the control, co-expression of CD80 and
      CD86 (necessary for antigen presentation) on splenocytes together with a
      decreased expression of chemotaxis-related marker (CD195) was attenuated by
      exposure to the AlO NP, especially the long-type. Taken together, the data
      suggest that accumulation following a single IV injection with rod-types of AlO
      NP is strengthened by a high aspect ratio and, subsequently, this accumulation
      has the potential to influence immune functions in an exposed host.

PMID- 27042763
TI  - Abnormalities in Diffusional Kurtosis Metrics Related to Head Impact Exposure in
      a Season of High School Varsity Football.
AB  - The purpose of this study was to determine whether the effects of cumulative head
      impacts during a season of high school football produce changes in diffusional
      kurtosis imaging (DKI) metrics in the absence of clinically diagnosed concussion.
      Subjects were recruited from a high school football team and were outfitted with
      the Head Impact Telemetry System (HITS) during all practices and games.
      Biomechanical head impact exposure metrics were calculated, including: total
      impacts, summed acceleration, and Risk Weighted Cumulative Exposure (RWE). Twenty
      four players completed pre- and post-season magnetic resonance imaging, including
      DKI; players who experienced clinical concussion were excluded. Fourteen subjects
      completed pre- and post-season Immediate Post-Concussion Assessment and Cognitive
      Testing (ImPACT). DKI-derived metrics included mean kurtosis (MK), axial kurtosis
      (K axial), and radial kurtosis (K radial), and white matter modeling (WMM)
      parameters included axonal water fraction, tortuosity of the extra-axonal space,
      extra-axonal diffusivity (De axial and radial), and intra-axonal diffusivity
      (Da). These metrics were used to determine the total number of abnormal voxels,
      defined as 2 standard deviations above or below the group mean. Linear regression
      analysis revealed a statistically significant relationship between RWE combined
      probability (RWECP) and MK. Secondary analysis of other DKI-derived and WMM
      metrics demonstrated statistically significant linear relationships with RWECP
      after covariate adjustment. These results were compared with the results of DTI
      derived metrics from the same imaging sessions in this exact same cohort. Several
      of the DKI-derived scalars (Da, MK, K axial, and K radial) explained more
      variance, compared with RWECP, suggesting that DKI may be more sensitive to
      subconcussive head impacts. No significant relationships between DKI-derived
      metrics and ImPACT measures were found. It is important to note that the
      pathological implications of these metrics are not well understood. In summary,
      we demonstrate a single season of high school football can produce DKI measurable
      changes in the absence of clinically diagnosed concussion.

PMID- 27042764
TI  - Immunohistochemical assessment of ezrin and moesin in colorectal carcinoma.
AB  - Ezrin and moesin are important molecules of the ERM family of proteins, which
      regulate cell adhesion and migration. The aim of this study was to evaluate the
      intensity and pattern of ezrin and moesin expression in colorectal carcinoma
      (CRC) together with correlating their expression with the clinico-pathologic
      features of this neoplasm. This study was carried out on 48 CRC and 10 adenoma
      specimens. All adenoma and 95% of CRC cases showed both ezrin and moesin
      expression. Ezrin was predominantly cytoplasmic in adenoma cases in comparison to
      membranous localization in carcinoma cases. Moesin was predominantly expressed in
      stroma (inflammatory cells and fibroblasts) in carcinoma (89.1%) compared with
      adenoma (50%). High H-score of ezrin expression was associated with
      adenocarcinoma type (P = .024) and was inversely correlated with mitotic count (P
      = .005). High H-score of moesin expression was associated with early Dukes
      staging of CRC (P = .016), absence of lymph node involvement (P = .022), and low
      number of involved lymph nodes (P = .04). The association of ezrin with favorable
      prognostic parameters may be due to its prominent membranous localization. The
      stroma of CRC could stand against invasion by expression of moesin. Ezrin and
      moesin are independently expressed from each other. 

PMID- 27042765
TI  - Old and new results about single-photon sensitivity in human vision.
AB  - It is sometimes said that 'our eyes can see single photons'. This article begins
      by finding a more precise version of that claim and reviewing evidence gathered
      for it up to around 1985 in two distinct realms, those of human psychophysics and
      single-cell physiology. Finding a single framework that accommodates both kinds
      of result is then a nontrivial challenge, and one that sets severe quantitative
      constraints on any model of dim-light visual processing. This article presents
      one such model and compares it to a recent experiment. 

PMID- 27042766
TI  - Triiodothyroacetic Acid Treatment in MCT8 Deficiency: A Word of Nuance.

PMID- 27042767
TI  - Experiences of working from a freestanding position as a case manager when
      supporting clients in the Swedish welfare system.
AB  - The Swedish state uses a case management function known as Personligt Ombud (PO).
      The role as PO differs from the traditional professional roles. It has a
      freestanding position in the welfare system. The aim of this study was to
      investigate POs' experiences of working from a freestanding position when
      supporting clients. Telephone interviews were conducted with 22 POs across
      Sweden. The interviews were recorded, transcribed, and analyzed by latent
      qualitative content analysis. The findings were reflected in three categories -
      freedom-promoted flexibility, surfing through a complex welfare system, and
      working for legitimacy. POs developed a holistic view to both the client as well
      as to the welfare system. POs experienced solely representing the client, which
      is a positive feature because part of the POs' role is advocating for the clients
      rights. The PO service differs from the PO service from other existing case
      management models and may need to develop strategies for decision-making and
      support in their own role. For example, they may use group supervision teams or
      'reflective teams'. The freestanding position may also entail problems in terms
      of lack of legitimacy. It is important for POs to develop good platforms with the
      surrounding actors among others things to improve the co-ordination process. It
      could be interesting if the PO model would be tested in other countries that have
      a fragmented welfare system. The PO model may also be useful to other 'target
      groups' who are in need of co-ordinated rehabilitation services. 

PMID- 27042768
TI  - Simulation training to teach postpartum hemorrhage surgery to residents.
AB  - OBJECTIVE: Description of the aims, the framework and the results of a postpartum
      hemorrhage surgery workshop for residents. STUDY DESIGN: This article is the
      first publication to describe a simulation workshop for the surgical management
      of maternal hemorrhage. Training was divided into both theoretical and practical
      workshops. Four obstetrician-gynecologists supervised residents who performed all
      the surgical procedures on a cadaver. This training course included the oldest
      residents at the Faculty of Medicine of Lille and was evaluated by participants
      using pre-test and post-test questionnaires. Medical knowledge was also
      evaluated. RESULTS: The pre-test questionnaire showed that medical knowledge for
      the treatment of postpartum hemorrhage was acceptable but that real practice was
      lacking. Eighty-six percent of the residents responded that they were not able
      deal with the situation correctly and most considered it stressful. The post-test
      questionnaire showed that training greatly improved the participants' theoretical
      knowledge and technical skills as well as significantly improving self
      confidence. CONCLUSIONS: Based on these positive results this workshop will be
      included in the resident training program and also be extended to professionals
      as a part of the continuing medical education program.

PMID- 27042769
TI  - Effect of vitamin C on collagen structure of cardinal and uterosacral ligaments
      during pregnancy.
AB  - OBJECTIVE: This study aimed to investigate changes in collagen structure in the
      cardinal and uterosacral ligaments of rats that were administered vitamin C
      during pregnancy. STUDY DESIGN: Eighteen female rats were divided into three
      groups: six pregnant rats administered 1.25mg/ml/day of vitamin C during
      pregnancy (Group A); six non-pregnant rats that were not administered vitamin C
      (Group B); and six pregnant rats that were not administered vitamin C during
      pregnancy (Group C). Fifteen days after delivery, the uteruses of all rats were
      removed. The intensity of staining (mild, moderate or severe) and the extent of
      positive staining areas (%) of type I and type III collagen H scores for types I
      and III collagen, and intensity of elastin fibres in the cardinal and uterosacral
      ligaments were investigated immunohistochemically. Differences between groups
      were analysed using Kruskal-Wallis and independent samples tests. RESULTS: The
      intensity and extent of type I and type III collagen, the H scores for type I and
      type III collagen, and the ratio of type III collagen H score: type I collagen H
      score differed significantly between groups. Pregnant rats administered vitamin C
      (Group A) had significantly higher values compared with non-pregnant rats (Group
      B): intensity of type I collagen (p=0.001), extent of type I collagen (p<=0.001),
      H score for type I collagen (p<=0.001), intensity for type III collagen
      (p=0.002), extent of type IV collagen (p=0.007), H score for type III collagen
      (p=0.017), type III collagen H score: type I collagen H score (p=0.039) and
      intensity of elastin fibres (p=0.097). A significant difference in the ratio of
      type III collagen H score: type I collagen H score was found between pregnant
      rats administered vitamin C (Group A) and pregnant rats not administered vitamin
      C (Group C) (p=0.002). CONCLUSIONS: The administration of vitamin C to rats
      during pregnancy had a favourable impact on collagen structure in the cardinal
      and uterosacral ligaments, suggesting that vitamin C supplementation during
      pregnancy may help to prevent pelvic organ prolapse and stress urinary
      incontinence.

PMID- 27042770
TI  - Colposcopists' experiences of HPV Test of Cure for the follow up of cervical
      intra-epithelial neoplasia.
AB  - OBJECTIVE: To survey lead colposcopists in England to explore their views on the
      recently introduced HPV Test of Cure (TOC) following treatment for cervical intra
      epithelial neoplasia (CIN) and to determine the extent to which it has impacted
      their clinical practice and affected their patients. METHODS: An online survey
      was sent to lead colposcopists across England. Questions were asked focusing on
      the clinicians' confidence in the ability of TOC to guide follow up in various
      clinical scenarios and how the implementation of TOC had changed patient
      management. RESULTS: There was a 50% (N=88) response rate. 90% of respondents
      indicated they were happy with the new procedure. In the follow-up questions, 20%
      indicated they were uncomfortable with the procedure when it was applied to women
      who were CIN2+ with incomplete excision at the endocervical margin. Open-ended
      questions elicited positive aspects of TOC including reduced follow-up, increased
      reassurance for patients and clinicians and a faster return to the call-recall
      system. Negative observations included concerns around HPV positive cases,
      possible false negatives and anxiety in those women who were originally subject
      to the pre-TOC guidelines and were now returned to call-recall "earlier" than
      originally indicated to them. 11% of respondents also indicated they work around
      the new guidelines to some extent. CONCLUSION: Although clinicians are on the
      whole positive towards the introduction of TOC, concerns were raised which centre
      primarily around those patients with CIN2+ combined with positive endocervical
      margins, issues related to HPV positive cases and the possibility of a false
      negative HPV result. The possibility of patient anxiety due to return to routine
      screening earlier than originally expected was also identified as a concern.

PMID- 27042771
TI  - Anticipation measures of sequence learning: manual versus oculomotor versions of
      the serial reaction time task.
AB  - The serial reaction time (SRT) task has generated a very large amount of
      research. Nevertheless the debate continues as to the exact cognitive processes
      underlying implicit sequence learning. Thus, the first goal of this study is to
      elucidate the underlying cognitive processes enabling sequence acquisition. We
      therefore compared reaction time (RT) in sequence learning in a standard manual
      activated (MA) to that in an ocular activated (OA) version of the task, within a
      single experimental setting. The second goal is to use eye movement measures to
      compare anticipation, as an additional indication of sequence learning, between
      the two versions of the SRT. Performance of the group given the MA version of the
      task (n = 29) was compared with that of the group given the OA version (n = 30).
      The results showed that although overall, RT was faster for the OA group, the
      rate of sequence learning was similar to that of the MA group performing the
      standard version of the SRT. Because the stimulus-response association is
      automatic and exists prior to training in the OA task, the decreased reaction
      time in this version of the task reflects a purer measure of the sequence
      learning that occurs in the SRT task. The results of this study show that eye
      tracking anticipation can be measured directly and can serve as a direct measure
      of sequence learning. Finally, using the OA version of the SRT to study sequence
      learning presents a significant methodological contribution by making sequence
      learning studies possible among populations that struggle to perform manual
      responses.

PMID- 27042772
TI  - Outcomes of arteriovenous fistula creation, effect of preoperative vein mapping
      and predictors of fistula success in incident haemodialysis patients: A single
      centre experience.
AB  - AIM: Vascular access in haemodialysis is critical for effective therapy. We aim
      to evaluate the outcomes of arteriovenous fistula (AVF) creation in incident
      haemodialysis patients, impact of preoperative vein mapping and predictors of
      successful AVF maturation in our centre. METHODS: Data of End-stage Renal Disease
      (ESRD) patients initiated on haemodialysis from January 2010 to December 2012 in
      our centre were retrospectively obtained from electronic medical records and
      clinical notes. Demographic characteristics, medical comorbidities, perioperative
      details were collected, and patients were followed up until 1 January 2014.
      RESULTS: A total of 708 patients (median age 64, IQR 55-72) were included with
      mean duration of follow up of 2.3 +/- 1.2 years, with access of AVF and
      arteriovenous graft (AVG) in 694 (98%) and 14 (2%) patients respectively. Eight
      patients were lost to follow-up. Successful AVF maturation was achieved in 542
      patients (78%), with 1-year cumulative patency rate of 74%. Multivariate analysis
      revealed male gender, upper arm AVF and good postoperative thrill and pulse as
      predictors of successful AVF maturation. Preoperative vein mapping was performed
      in 42.5% (295/694) of patients, with mean vein diameter of 2.44 +/- 0.82 mm.
      Maturation rates with and without vein mapping were 72.2% and 82.4%,
      respectively, (P = 0.001). In patients with vein diameters of <2 mm and >=2 mm,
      there was no statistically significant difference in maturation rates (71.3% vs.
      72.6%; P = 0.887) and median maturation time (66 vs. 78 days; P = 0.73).
      CONCLUSION: Arteriovenous fistula can be successfully created in most incident
      haemodialysis patients. Routine vein mapping is not necessary if veins are
      suitable on physical examination alone, and vein sizes of <2 mm on ultrasound is
      not associated with lower AVF maturation rate.

PMID- 27042773
TI  - Hepatocellular adenoma with malignant transformation in a patient with neonatal
      portal vein thrombosis.

PMID- 27042774
TI  - Synthetic Self-Assembled Materials in Biological Environments.
AB  - Synthetic self-assembly has long been recognized as an excellent approach for the
      formation of ordered structures on the nanoscale. Although the development of
      synthetic self-assembling materials has often been inspired by principles
      observed in nature (e.g., the assembly of lipids, DNA, proteins), until recently
      the self-assembly of synthetic molecules has mainly been investigated ex vivo.
      The past few years however, have witnessed the emergence of a research field in
      which synthetic, self-assembling systems are used that are capable of operating
      as bioactive materials in biological environments. Here, this up-and-coming
      field, which has the potential of becoming a key area in chemical biology and
      medicine, is reviewed. Two main categories of applications of self-assembly in
      biological environments are identified and discussed, namely therapeutic and
      imaging agents. Within these categories key concepts, such as triggers and
      molecular constraints for in vitro/in vivo self-assembly and the mode of
      interaction between the assemblies and the biological materials will be
      discussed. 

PMID- 27042775
TI  - An Update on the Use of Barbed Suture in Minimally Invasive Gynecological Surgery
      (MIGS).
AB  - The use of barbed suture has enabled general and minimally invasive gynecological
      surgery (MIGS) surgeons to close surgical wounds more efficiently with minimal
      complications. This article reviews developments in barbed (knotless) sutures and
      related devices. 

PMID- 27042776
TI  - The Science of Hyperbaric Oxygen for Flaps and Grafts.
AB  - Hyperbaric oxygen (HBO) therapy is a versatile modality that has applications
      across several medical fields. HBO therapy has become a valuable asset in the
      management of compromised tissue grafts and flaps. Although classified together,
      grafts and flaps are distinctly different, in that grafts depend on the wound bed
      for revascularization, whereas flaps have an inherent blood supply. Evidence has
      shown that in a compromised graft suffering from hypoxia, HBO can maximize
      viability and reduce the need for repeat grafting. By comparison, compromised
      flaps can suffer from both ischemic and reperfusion injury, which can also be
      attenuated by HBOT to maximize viability. The beneficial effects of HBO occur by
      several mechanisms, including hyper-oxygenation, fibroblast proliferation,
      collagen deposition, angiogenesis, and vasculogenesis. Animal studies have
      demonstrated several of these mechanisms, including an increase in the number,
      size, and growth distance of blood vessels after HBO. Likewise, clinical studies
      have found positive responses in multiple types of tissue grafts and flaps, with
      some cases involving irradiated fields. Altogether, the data emphasizes that
      early identification of flap or graft compromise is absolutely critical, with
      maximized chance for viability when HBO is initiated as soon as possible. 

PMID- 27042777
TI  - Patient Outcomes Following Injury from Hysteroscopic Sterilization.
AB  - OBJECTIVE: We present clinical data on two patients who underwent hysteroscopic
      sterilization (HS) 11 years apart using the Essure(r) (Bayer Inc., Whippany, NJ)
      device. MATERIALS AND METHODS: Symptoms and resolution are described for
      symptomatic Essure(r) patients. RESULTS: Case 1 (G3P1) underwent HS in 2004 at
      age 21. Performed in a physician's office without anesthesia, HS involved
      placement of >2 Essure(r) devices which was followed by severe, unrelenting
      pelvic pain. Confirmatory hysterosalpingogram (HSG) three months after HS
      revealed five devices. Surgical costs for laparoscopic assisted vaginal
      hysterectomy (LAVH) were fully reimbursed by the device manufacturer seven months
      later. Case 2 (G8P4) underwent HS in 2015 at age 32. One year earlier, the
      patient's right fallopian tube was removed due to ectopic pregnancy. Essure(r)
      devices were placed bilaterally in a physician's office without anesthesia; HS
      was accompanied by sharp pelvic pain. The patient obtained HSG three weeks after
      HS due to constant discomfort. Bilateral tubal occlusion was verified, but
      abnormal device loop configuration suggesting myometrial penetration was noted on
      the right. At laparoscopy, the left Essure(r) device was excised intact but the
      right coil could not be located. Thus far, there has been no offer in Case 2 from
      the device manufacturer to offset medical expenses. CONCLUSIONS: While HS has
      been FDA approved for use in the United States since 2002, this is the first
      description of clinical sequela when FDA labeling for the Essure(r) procedure is
      ignored. These cases illustrate the importance of proper physician training in HS
      and underscore the need for improved tracking of Essure(r) associated symptoms.

PMID- 27042778
TI  - Effect of Varying Posterior Cruciate Ligament (PCL) Recessions on Kinematics and
      Ligament Strains with Cruciate Retaining Total Knee Prostheses.
AB  - INTRODUCTION: Proper ligament tension in flexion with posterior cruciate
      retaining (CR) total knee arthroplasty (TKA) has long been associated with
      clinical success. The purpose of this study was to determine the effect of
      varying levels of posterior cruciate ligament (PCL) release on the tibiofemoral
      kinematics and PCL strain. MATERIALS AND METHODS: A computational analysis was
      performed and varying levels of PCL release were simulated. Tibiofemoral
      kinematics was evaluated. The maximum PCL strain was determined for each bundle
      to evaluate the risk of rupture based on the failure strain. RESULTS: The femoral
      AP position shifted anteriorly as the PCL stiffness was reduced. PCL strain in
      both bundles increased as stiffness was reduced. The model predicts that the AL
      bundle should not rupture for a 75% release. Risk of PM bundle rupture is greater
      than AL bundle. DISCUSSION: Our findings suggest that a partial PCL release
      impacts tibiofemoral kinematics and ligament tension and strain. The relationship
      is dynamic and care should be taken when seeking optimal balance intra
      operatively.

PMID- 27042779
TI  - Intra-operative Use of Hemopatch(r): Interim Results of a Nationwide European
      Survey of Surgeons.
AB  - INTRODUCTION: Haemostasis is a critical part of surgery. Haemostatic agent
      selection is based upon a number of factors including surgeon's experience and
      choice. This post-marketing survey determined surgeons' intraoperative use and
      perception of Hemopatch(r) (Baxter Healthcare Corporation, Deerfield, IL), a
      resorbable collagen-based sealing haemostat. METHODS AND PARTICIPANTS: A one-arm
      questionnaire was distributed to European general, cardiac, pulmonary, and
      urologic surgeons who used Hemopatch(r) to achieve haemostasis in situations
      where bleeding control by pressure, ligature, or conventional procedures had been
      ineffective or was impractical. Responses were summarized for patient
      characteristics, surgical procedures/techniques, and surgeons' assessment of
      Hemopatch(r) regarding their overall satisfaction and utilization characteristics
      of Hemopatch(r). RESULTS: Of 1028 responses received from seven European
      countries, the majority were from Germany (47.3%) or Italy (36%). Most cases were
      in males (60.7%), 50-75 years of age (61.8%), performed by an open approach
      (82.5%), with 52.7% general-, 16.2% cardiac-, 7.5% lung, 19.5% urologic-type
      procedures and 3.7% other/unknown. Successful haemostasis after two minutes of
      approximation occurred in 93.3% of patients (86.8%-96.9% across surgical
      subtypes), with similar rates by approach (93.1% open; 94.1% minimally-invasive),
      and patient's use of anticoagulant and/or antiplatelet agents (87.9% - 93.1%).
      Over 92% of surgeon's rated Hemopatch(r) as "excellent" or "good" in assessments
      of overall satisfaction, haemostasis efficacy, ease of preparation, ease of
      handling, flexibility/pliability, and tissue adherence. These characteristics
      were rated as excellent or good by 81% or more of surgeons in analyses by
      surgical subspecialty and surgical approach of open or minimally invasive.
      CONCLUSIONS: Hemopatch(r) provides effective haemostasis across a variety of
      surgical procedures, both in open- and minimally-invasive, as well as in patients
      receiving anticoagulant and/or antiplatelet agents. Surgeon's generally rated
      their overall satisfaction with Hemopatch(r), its haemostatic efficacy, and other
      characteristics as "much better" or "better" than their previously used
      haemostat.

PMID- 27042780
TI  - An Assessment of the Comprehensiveness of Various Hip Outcome Scores.
AB  - INTRODUCTION: Evaluating outcomes following total hip arthroplasty (THA) has been
      essential for improving satisfaction and quality of care. However, finding
      systems that fully encompass these outcomes poses a challenge for physicians, and
      often still do not provide an adequate picture of a patient's recovery.
      Therefore, we evaluated different scoring systems to determine the most efficient
      method of assessing the outcomes of patients undergoing THA. MATERIALS AND
      METHODS: We evaluated all hip scoring systems currently available in the
      literature and identified the parameters assessed in the questionnaires. The
      parameters were then subdivided into subjective, objective, rehabilitative, and
      quality of life outcome measures. We identified the most commonly referenced
      questionnaires and assessed multiple permutations of these with other scoring
      systems to determine the combinations that would most efficiently and
      comprehensively evaluate the outcomes of patients undergoing THA. RESULTS: The 42
      identified scoring systems covered the following parameters: 4 subjective, 5
      objective, 17 rehabilitative, and 18 quality of life. The Harris Hip Score (HHS)
      was the most cited system (5,613), but the Hip Disability and Osteoarthritis
      Outcome Score (HOOS) had the greatest coverage of all the parameters (49%). On
      combinatorial analysis, the 2-, 3-, and 4-item permutations that had the greatest
      coverage were HOOS and 36-Item Short-Form Health Survey (SF-36) (59%), HOOS, SF
      36, and Larson (75%), and HOOS, SF-36, Larson, and Lower Extremity Functional
      Scale (LEFS) (80%). CONCLUSION: Physicians and researchers have attempted to
      fully assess the outcomes of patients undergoing THA. Utilizing existing scoring
      systems in particular combinations may allow us to form an ideal questionnaire
      that provides sufficient coverage of parameters, thus providing a more
      comprehensive way to cost-effectively evaluate outcomes. Further analysis is
      required to determine whether or not these permutations provide a sufficient
      evaluation in a clinical setting.

PMID- 27042781
TI  - Outcomes of Second-Generation Tapered Wedge Femoral Stem.
AB  - INTRODUCTION: Newer generation cementless femoral stems have been designed to
      emulate more precisely the anatomy of the native femur. However, few studies have
      evaluated these designs. The purpose of this study was therefore to evaluate
      outcomes of primary total hip arthroplasty (THA) in patients who received a
      second-generation, tapered wedge stem by analyzing (1) all-cause and aseptic
      implant survivorships; (2) clinical and patient-reported outcomes; (3)
      radiographic outcomes; and (4) incidence of complications. MATERIALS AND METHODS:
      We evaluated 202 primary THA patients (37% men, 63% women) who had a mean age of
      63 years (range, 18 to 88) and a mean body mass index (BMI) of 29 (range, 18 to
      40). All patients underwent THA using a press-fit, tapered wedge stem with a
      morphometric design containing a size-specific medial curvature, which optimizes
      initial press-fit stability. Kaplan-Meier analysis was performed to determine
      implant survivorship, and Harris Hip Scores (HHS) and the Short form-36 (SF-36)
      were used to evaluate clinical and patient-reported outcomes. Early
      postoperatively and annually thereafter, pelvic radiographs were reviewed for
      evidence of osteolysis or loosening. Complications were identified through a
      comprehensive chart review and were classified as either surgical or medical.
      RESULTS: At final follow-up, the all-cause and aseptic survivorships for the
      femoral stem were 99.5% and 100%, respectively. At final follow-up, the mean HHS
      was 87 (range, 35 to 100). The SF-36 mental and physical component scores were 47
      (range, 19 to 65) and 47 (range, 23 to 65), respectively, at final follow-up. No
      progressive radiolucencies or loosening were observed. Surgical complications
      included nerve palsy, posterior trochanteric avulsion, arthrofibrosis, and
      periprosthetic fracture. The only medical complication was acute renal failure.
      CONCLUSION: This second-generation stem demonstrated excellent short-term
      survivorship and functional outcomes. The improved patient fit of this stem may
      yield continued favorable results with longer-term follow-up.

PMID- 27042782
TI  - Long-Term Survivorship and Clinical Outcomes of a Single Radius Total Knee
      Arthroplasty.
AB  - INTRODUCTION: To ensure the continued success of total knee arthroplasties
      (TKAs), we must employ ever-evolving modifications to our techniques and implant
      designs. As part of this process, a knee prosthesis with a single radius (SR) has
      been developed to more precisely emulate the anatomy and biomechanics of the
      native knee, but there is little data on long-term outcomes. Therefore, the
      purpose of this study was to evaluate (1) the long-term (10-year) survivorship;
      (2) clinical and patient-reported outcomes; (3) radiographic outcomes; and (4)
      incidence of complications in patients who underwent TKA with this SR prosthesis.
      MATERIALS AND METHODS: We evaluated 54 patients (67 TKAs) (24% men, 76% women)
      who had a mean age of 62 years at the time of surgery (range, 30 to 82 years).
      The mean follow-up was 10 years (minimum 9 years). All patients underwent a
      primary TKA using a newly developed single radius implant with posterior condylar
      flare. Kaplan-Meier analysis was performed to determine implant survivorship. The
      Knee Society Score (KSS), University of California Los Angeles (UCLA) activity
      scale, and Short Form-36 (SF-36) mental and physical component scores were used
      to evaluate clinical and patient-reported outcomes. Anteroposterior and lateral
      radiographs were reviewed for evidence of component loosening. Complications were
      identified through a comprehensive chart review and were classified as either
      surgical or medical. RESULTS: Assessment of aseptic loosening revealed that
      survivorship of the tibial and femoral components was 100%. Evaluation of
      revisions for any reason showed that Kaplan-Meier aseptic and all-cause
      survivorship of the femoral and tibial components was 99%. When only polyethylene
      exchanges were included, the all-cause overall and aseptic survivorships were 94%
      and 96% respectively. Additionally, the mean KSS and UCLA activity scores were 64
      (range, 5 to 100 points) and 5 points (range, 1 to 9 points) at final follow-up.
      The mean SF-36 mental and physical component scores were 53 (range, 23 to 66
      points) and 39 points (range, 15 to 61 points). Surgical complications included
      arthrofibrosis, extensor mechanism disruption, patellar component revision, and
      peroneal nerve palsy. No medical complications were reported. CONCLUSION: Single
      radius total knee arthroplasties have demonstrated excellent long-term
      survivorship and functional outcomes, as demonstrated by this preliminary report.

PMID- 27042783
TI  - Time Burden of Standardized Hip Questionnaires.
AB  - INTRODUCTION: Many standardized scales and questionnaires have been developed to
      assess outcomes of patients undergoing total hip arthroplasty (THA). However,
      these surveys can be a burden to both patients and orthopaedists as some are time
      inefficient. In addition, there is a paucity of reports assessing the time it
      takes to complete them. In this study we aimed to: (1) assess how long it takes
      to complete the most common standardized hip questionnaires; (2) determine the
      presence of variation in completion time; and (3) evaluate the effects of age,
      gender, and level of education on completion time. MATERIALS AND METHODS: Based
      on a previous study, we selected the seven most commonly used hip scoring systems
      Western Ontario and McMaster Universities Hip Outcome Assessment (WOMAC), Harris
      Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), Larson
      Score, Short-form 36 (SF-36), modified Merle d'Aubigne and Postel Score (MDA),
      and Lower Extremity Functional Scale (LEFS). The standardized scales and
      questionnaires were randomly administered to 70 subjects. The subjects were
      unaware that they were being timed during completion of the questionnaire. We
      obtained the coefficients of variation of time for each questionnaire. The mean
      time to complete the questionnaire was then stratified and compared based on age,
      gender, and level of education. RESULTS: The mean time to complete each of the
      systems is listed in ascending order: Modified Merle d'Aubigne and Postel Score
      (MDA), Lower Extremity Functional Scale (LEFS), Western Ontario and McMaster
      Universities Hip Outcome Assessment (WOMAC), Harris Hip Score (HHS), Larson
      Score, Hip Disability and Osteoarthritis Outcome Score (HOOS), and Short-form 36
      (SF-36). The WOMAC and Larson Score coefficients of variation were the largest,
      and the HOOS and MDA were the smallest. There was a significantly higher mean
      time to completion in those who were above or equal to the age of 55 years as
      compared to those who were below the age of 55 (227 vs. 166 seconds). There was
      no significant association found in time of completion between gender or
      education level. CONCLUSION: Standardized scales and questionnaire which assess
      THA patients can be burdensome and time-inefficient, which may lead to task
      induced fatigue. This may result in inaccurate THA patient assessments, which do
      not reflect the patient's true state. Future studies should aim to create an
      encompassing questionnaire that is time efficient and can replace all currently
      used validated systems.

PMID- 27042784
TI  - What Influences How Patients Rate Their Hospital After Total Knee Arthroplasty?
AB  - INTRODUCTION: There is increasing pressure from Centers for Medicare and Medicaid
      Services (CMS) to report quality measures for all hospitalizations. These quality
      measures are determined based on results from satisfaction surveys, such as Press
      Ganey(r) (PG) (Press Ganey(r) Performance Solutions, Wakefield, Massachusetts).
      Included in this particular survey element are questions regarding staff,
      including nurses and doctors, as well as items such as pain control. The results
      of these surveys will dictate the amount doctors are compensated for their
      services. Therefore, this study was undertaken to evaluate the effect of treating
      orthopaedists and nurses, as well as pain control, on PG surveys in patients who
      underwent total knee arthroplasty (TKA). Specifically, we aimed to ascertain the
      effect of these factors on how post-TKA patients perceive: 1) their orthopaedist,
      and 2) their overall surgical experience. MATERIALS AND METHODS: We queried the
      Press Ganey(r) Database for all patients who underwent a TKA at our institution
      between November 2009 and January 2015. A weighted mean of question domains was
      utilized since each had multiple questions. In order to assess if pain management
      influences orthopaedist perception, a correlation analysis was performed between
      pain control and perception. In order to assess the influence of pain management
      on surgical experience, we performed a correlation analysis between pain control
      and overall hospital rating. A multiple regression analysis was performed using
      the hospital rating as the dependent variable to determine the most influential
      factors on surgical experience. RESULTS: Our analysis demonstrated a
      significantly positive correlation between patient perception of their pain
      control and their orthopaedist. There was a significant positive correlation
      between patient's perception of their pain control and their overall surgical
      experience. Multiple regression analysis using overall surgical experience as the
      dependent variable demonstrated a significant positive influence of perception of
      nurses and orthopaedists. Pain management positively influenced surgical
      experience; however, this was not significant. CONCLUSIONS: We found that
      perception of pain control in post-TKA patients affects perception of the
      treating orthopaedists, as well as their overall surgical experience. In
      addition, perception of orthopaedists and nurses both outweigh perception of pain
      control on overall surgical experience, with nurses being the most important.
      Orthopaedists should focus on staff education-particularly nurses-and educate
      them in order to optimize results on PG surveys and, ultimately, improve patient
      satisfaction. Further studies should correlate current standardized scoring
      systems and questionnaires for TKA with PG surveys in order to recognize gaps
      that need to be bridged to improve post-TKA patient satisfaction.

PMID- 27042785
TI  - Initial Experience with a New Macroporous Partially Absorbable Mesh: Introducing
      Ultrapro(r) AdvancedTM.
AB  - INTRODUCTION: The Ultrapro(r) AdvancedTM mesh (Ethicon, Sommerville, NJ) is a new
      mesh design, using the best characteristics from the previous platform, while
      adding new, advanced features. Our centre, Imelda Hospital, Bonheiden, Belgium,
      was chosen as one of the first clinical testing sites. The aim of this study was
      to present our preliminary data on complication rate and patient satisfaction.
      MATERIALS AND METHODS: From October 1, 2015 until January 31, 2016, we treated 57
      patients, implementing 67 Ultrapro(r) AdvancedTM meshes. One patient was excluded
      due to postoperative cerebral haemorrhage with aphasia. Only patients with more
      than one-month follow-up were included for further analysis, resulting in a
      population of 41 patients with 51 meshes. Of them, 35 were male and only 6 were
      female, with an average age of 61.4 years and an average BMI of 25.9. The
      indications were uni- and bilateral laparoscopic inguinal hernia repair (n = 23
      and 10 respectively), open inguinal hernia repair (n = 3), and open incisional
      hernia repair (n = 5). Quality of life was measured preoperatively and at four
      weeks postoperatively, using the hernia specific Carolina Comfort Scale (CCS)
      questionnaire. RESULTS: The primary endpoint was complication rate. Only two
      patients (4.8%) mentioned a mild scrotal hematoma and two patients (4.8%)
      demonstrated a seroma. There were no superficial wound infections nor early
      recurrent hernias. Our secondary endpoint was quality of life, measured by the
      CCS questionnaire, which differentiates between a symptomatic and an asymptomatic
      group. A total of 13 patients were asymptomatic, whilst 28 patients reported some
      sort of discomfort, ranging from mild (n = 25) to moderate and/or daily symptoms
      (n = 3). No patients were disabled by their symptoms. CONCLUSION: The Ultrapro(r)
      AdvancedTM is a sequel of the classic Ultrapro(r) mesh with similar
      characteristics: it is a "lightweight", macroporous, partially absorbable mesh
      built out of thin filaments, while maintaining sufficient strength. Its
      improvement is due to incorporation of evidence-based characteristics such as an
      increased mesh elasticity. Furthermore, the surgical manipulation is improved
      thanks to the increased mesh memory. Our prospective cohort study shows good
      initial and short-term results after implementation of the Ultrapro(r)
      AdvancedTM. However, further prospective research is mandatory on the long-term
      outcomes.

PMID- 27042786
TI  - Reducing Opioid Adverse Events: A Safe Way to Improve Outcomes.
AB  - INTRODUCTION: Opioids are commonly used in the postoperative period to manage
      postsurgical pain. However, adverse side effects of opioids include respiratory
      depression, urinary retention, pruritus, vomiting, nausea, constipation, and
      increased risk of falls. Surgical site infiltration with extended release
      liposomal bupivacaine is effective in the multimodal care plan of managing
      postsurgical patients. The purpose of the present study was to examine the
      possible effects of liposomal bupivacaine on postoperative opioid adverse events
      following open hernia repair and laparoscopic colon resection surgery. MATERIALS
      AND METHODS: The study population comprised 82 patients who had undergone open
      hernia repair or a laparoscopic colon resection. Forty-five of the 82 patients
      were treated with liposomal bupivacaine. Data were examined retrospectively from
      January 1, 2012 to August 31, 2012 in comparison with historical controls.
      Adverse opioid events measured included constipation, pruritus, vomiting, nausea,
      urinary retention, respiratory depression and fall risk. Statistical tools used
      were the Mann-Whitney U test, Pearson's chi-squared test, and Fisher's exact
      test. RESULTS: The addition of liposomal bupivacaine did significantly (p<0.05)
      reduce urinary retention and respiratory depression. Additionally, from the
      perspective of hospital safety there was a significant reduction in patients at
      high risk of falls, from 16% to 8.4% as well as an increase in patients at low
      risk of falls, from 37.6% to 48.7%. CONCLUSION: The findings of this study
      demonstrate that using liposomal bupivacaine can significantly reduce high-risk
      fall patients, increase low-risk fall patients as well as decrease urinary
      retention and respiratory depression in the postoperative setting. Given
      heightened consideration of the impact of sentinel events on hospital
      reimbursement since health care reforms in 2014, these results are important
      because they can mitigate complications associated with opioids in postsurgical
      pain management, and thereby reduce the costs of hospitalization.

PMID- 27042787
TI  - A Meta-Analysis of Transcutaneous Electrical Nerve Stimulation for Chronic Low
      Back Pain.
AB  - OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) may provide a safe
      alternative to current side-effect-heavy narcotics and anti-inflammatories
      utilized in chronic low back pain. Therefore, we performed a meta-analysis to
      evaluate the efficacy of TENS for the treatment of chronic low back pain.
      MATERIALS AND METHODS: We included randomized controlled trials (RCTs), cohort
      studies, and randomized crossover studies on TENS for the management of low back
      pain. We utilized a visual analogue scale (VAS) for pain as our primary outcome.
      Effectiveness of treatment was quantified using improvement in outcome scores for
      each study. Of the studies that met the criteria, 13 allowed for calculation of
      weighted mean differences in pain reduction. We used a random model effect to
      evaluate changes in pain produced by the intervention. RESULTS: Included were
      nine level I and four level II, encompassing 267 patients (39% male) who had a
      mean follow-up of seven weeks (range; 2 to 24 weeks). The mean duration of
      treatment was six weeks (range; 2 to 24 weeks). The standardized mean difference
      in pain from pre- to post-treatment for TENS was 0.844, which demonstrated
      significant improvement of TENS on pain reduction. When subdividing treatment
      duration, patients that were treated for < 5 weeks had significant effects on
      pain, while those treated for > 5 weeks did not. CONCLUSION: Treatment of chronic
      low back pain with TENS demonstrated significant pain reduction. The application
      of TENS may lead to less pain medication usage and should be incorporated into
      the treatment armamentarium for chronic low back pain.

PMID- 27042788
TI  - Polyvinylidene Fluoride Mesh (PVDF, DynaMesh(r)-IPOM) in The Laparoscopic
      Treatment of Incisional Hernia: A Prospective Comparative Trial versus Gore(r)
      ePTFE DUALMESH(r) Plus.
AB  - BACKGROUND: Laparoscopic approach is now generally accepted for the treatment of
      incisional hernia. The ideal mesh is still to be found. The aim of this study is
      to compare the well-known Gore(r) DUALMESH(r) Plus (WL Gore & Associates,
      Flagstaff, AZ) to a new prosthesis, the DynaMesh(r)-IPOM (FEG Textiltechnik GmbH,
      Aachen, Germany), to clinically verify its potential benefits in the laparoscopic
      treatment of incisional hernia. MATERIALS AND METHODS: Comparing the results of
      the laparoscopic treatment of two groups of patients affected by incisional
      hernia using Gore(r) DUALMESH(r) Plus and DynaMesh(r)-IPOM. RESULTS: There were
      45 females and 31 males, with age variable from 21 to 84 years of age. The two
      groups were well matched for age (median age 60 years for group A and 57.6 years
      for group B-p=0.44) and sex (28F and 17M group A and 13 F and 18 M group B
      p=0.008), while median BMI resulted slightly higher in group B (26.12 group A and
      29.74 group B-p=0.001). The median size of the defect was similar in the two
      groups (87.5 mm group A and 83.4 mm for group B-p=0.83), while the median
      operating time was slightly longer in group A (77 min group A and 67 min group B
      p=0.44). No difference in the length of hospital stay was evidenced between the
      two groups (3.19 days for group A and 3 days for group B-p=0.74). Time to return
      to physical activity was similar between the two groups (13.46 days for group A
      and 12.7 days for group B-p=0.32). Minor complications occurred in 15 cases
      (19.7%): seromas (7 cases), prolonged ileus (6 cases), and hemoperitoneum (2
      cases), without significant difference in the incidence of such complications in
      the two groups. Five recurrences (6.5% of cases) occurred. No differences in the
      recurrence rate was noted between the two groups (3 cases/7% for group A and 2
      cases/6% for group B-p=00.7). CONCLUSIONS: DynaMesh(r)-IPOM proved to be a safe
      and effective mesh for the laparoscopic repair of incisional hernia even when
      compared to DUALMESH(r) Plus.

PMID- 27042789
TI  - Mobile Application Use in Monitoring Patient Adherence to Perioperative Total
      Knee Arthroplasty Protocols.
AB  - The potential for using mobile applications (apps) as an effective tool to
      monitor patients in an outpatient setting is promising. Past studies have
      investigated the use of applications in preoperative and postoperative settings
      as well as in monitoring and treating chronic illnesses such as diabetes,
      congestive heart failure (CHF), and multiple sclerosis. However, there is limited
      data on its specific use in the context of total knee arthroplasty. Given the
      complicated nature and crucial role of patient adherence to protocols during the
      preparatory and recovery phases of the procedure, the use of an app can serve as
      a helpful tool in aiding patients throughout this process. We present a pilot
      study to assess the efficacy of using such an app in order to monitor patient
      adherence to total knee arthroplasty-specific preoperative and postoperative
      protocols. Preoperative protocols used in this study included a 5-item medication
      protocol and multiple activity instructions. Postoperative patient protocols
      included following instructions on topics such as recording responses to quality
      of-life questions, when and how to contact the clinical team if patients had non
      emergent concerns or questions, and carrying out daily physical therapy (PT)
      exercises. Patients received and recorded responses to these preoperative and
      postoperative instructions using the iGetBetter program application installed on
      an iPad Mini, provided to the participants. Patient adherence was based on the
      data gathered from the patient responses inputted on this app. Adherence rates
      were comparable to those reported in various past studies that also investigated
      rates of adherence to health management-related instructions communicated through
      mobile apps. 

PMID- 27042790
TI  - What Is the Efficacy of Repeat Manipulations Under Anesthesia to Treat Stiffness
      Following Primary Total Knee Arthroplasty?
AB  - BACKGROUND: Manipulation under anesthesia (MUA) can help post-total knee
      arthroplasty (TKA) patients who have knee stiffness regain range-of-motion.
      However, despite undergoing MUA, patients may have persistent knee stiffness.
      Often, this persistent knee stiffness is treated with a repeat MUA. Therefore,
      the purpose of this study was to evaluate repeat MUAs by assessing: (1)
      demographic characteristics, (2) range-of-motion, (3) clinical outcomes, and (4)
      rate of revision surgery in post-TKA patients with persistent knee stiffness who
      either underwent a single MUA or repeat MUAs. MATERIALS AND METHODS: One-hundred
      and-sixty-seven post-TKA who had undergone an MUA between 2005 and 2011 at two
      institutions were reviewed. Patients were stratified into those who had a single
      MUA (138 knees) and those who had a repeat MUA (29 knees). The mean follow-up
      period was 63 months (range, 36 to 90 months). The incidence of repeat MUA within
      this cohort was determined. Demographics and ROM were compared using Student t
      test and Chi-square as appropriate. Functional outcomes were assessed using Knee
      Society scores (KSS) and compared between the two cohorts. RESULTS: Among the 167
      patients who underwent a MUA, 29 (17%) required repeat manipulations. The repeat
      MUA cohort was younger and more likely to have osteonecrosis as the underlying
      cause of knee disease. For the repeat MUA cohort, 17 patients (59%) had achieved
      satisfactory mean gains in ROM after their repeat MUAs. These patients had also
      achieved excellent mean Knee Society objective and functional scores. However,
      another seven knees (24%) had further persistent knee stiffness requiring
      arthrolysis of adhesions and five patients (17%) had undergone revision of the
      polyethylene spacer or patellar component to improve range-of-motion. CONCLUSION:
      In this study, the majority of patients who had undergone a repeat MUA were able
      to achieve improvements in flexion range-of-motion and functional outcomes.
      However, the remaining patients required more invasive procedure to treat
      persistent knee stiffness. In patients who have persistent knee stiffness after
      MUAs, a repeat MUA may be helpful to increase range-of-motion and function.

PMID- 27042791
TI  - A Modified Fisherman's Knot for Laparoscopic Suturing.
AB  - Suturing is an essential surgical technique, because there is no resection
      without the need for reconstruction. Therefore, every surgeon should master a set
      of suturing techniques so he can adapt his approach to the specificity of the
      situation. The development of laparoscopic surgery poses a new challenge as not
      all open techniques are amendable for laparoscopic use. We would like to propose
      a modified fisherman's knot, which has been optimised in our center for
      laparoscopic use. The technique can be used with every monofilament non-braided
      wire. The needle is placed through the tissue to be sutured and both wires are
      externalised through the trocar. First, a simple knot is placed by crossing the
      left over the right wire. Next, the left is turned around the right wire four
      times proximal to the starting knot and crossed to the left wire where an
      additional two turns are made moving away from the trocar. The knot is closed
      gently, making sure not to lock the knot. Then the instrument of Drouard is used
      to gently glide the knot over the right wire back through the trocar into the
      abdomen. After making sure that adequate pressure has been delivered to the knot,
      to firmly close the tissue, the wire must be cut at a length of at least 3 mm. A
      new wire should be used for every knot and in this manner several knots can be
      delivered to make sure the tissue is adequately closed. In our center, no known
      complications due to loosening or failure of these knots have occurred since we
      incorporated this knotting technique into our daily practice more than 20 years
      ago. 

PMID- 27042792
TI  - Subcutaneous Destruction of Sinus Tract with Long-term Vessel Loop Drainage as a
      Minimally Invasive Surgical Treatment for Primary Pilonidal Sinus.
AB  - The surgical management of pilonidal disease ranges from minimally invasive
      techniques to wide excision with secondary wound healing. Hypothetical
      counterarguments for using the minimally invasive techniques are that these
      techniques only incompletely remove the sinus tract and that they allow the
      formation of subcutaneous cavities as a result of rapid closure of small skin
      incisions. In order to avoid these problems we used a vessel loop drainage after
      subcutaneous destruction of the sinus tract. In this technique we combined two
      procedures: a narrow excision of pilonidal orifices with the subcutaneous
      destruction of the sinus tract and the removal of hair as well as the long-term
      vessel loop drainage of the wound channel with repeated revisions of the wound
      channel for removing hair remnants. In order to assess the efficacy and morbidity
      of this method 5 patients with primary symptomatic pilonidal sinus underwent an
      operation as a pilot study. Up to the removal of the vessel loop the wound
      channel had been regularly inspected using a mosquito clamp. If during two
      successive inspections no hair from the wound was found the vessel loop was
      removed. No adverse events occurred such as abscess or recurrent pilonidal sinus.
      One female patient with a history of long-term use of morphine derivatives and
      psychotropic substances experienced persistent coccygeal pain that persisted
      longer than 6 weeks. The complete wound healing with the formation of a
      qualitative scar took place on the 21st postoperative day (for 3 patients) and on
      the 28th postoperative day (for 2 patients). Initial results suggest that this
      operation is an effective procedure for the treatment of primary simple pilonidal
      sinus disease and we will continue to systematically test it. 

PMID- 27042793
TI  - A New Reusable Platform for TransAnal Minimally Invasive Surgery: First
      Experience.
AB  - INTRODUCTION: TransAnal Minimally Invasive Surgery (TAMIS) has generated interest
      and attracted research in the last decade. This approach is used to treat primary
      benign and malignant diseases, but it can also be adopted to resolve colorectal
      complications, such as leak and fistula, bleeding and stenosis. A new reusable
      transanal platform formed by a new port and monocurved instruments has been
      invented and here presented. MATERIALS AND METHODS: The first experience included
      13 patients submitted to TAMIS for rectal adenocarcinoma (8), immediate
      colorectal leak (1), early rectovaginal fistula (1), late colorectal fistula (1),
      immediate colorectal bleeding (1), and benign stenosis (1). Mean age was 62.3
      years (38-74), and mean BMI was 25.2 kg/m2 (20.5-32.1). RESULTS: Mean operative
      time for transanal total mesorectal excision (TME) was 149.2 minutes (96-193) and
      for the other procedures 80.6 minutes (15-163). Mean operative bleeding was 51.1
      cc (0-450). Mean hospital stay was 5.0 days (2-8). The 3 patients with coloanal
      anastomosis presented diarrhea postoperatively. No other early postoperative
      complications were registered. Pathologic report in the oncologic diseases showed
      that a mean number of 14.7 nodes (16-20) were removed. After a mean follow-up of
      8 months (1-14), there were no late complications in any of the 13 patients
      treated. CONCLUSION: TAMIS is a feasible alternative approach to treat rectal
      cancer and a completely new technique to manage colorectal complications.
      Moreover, this new transanal platform offers surgeons a satisfactory working
      ergonomy, with no increase in cost of the procedures, because entirely reusable
      materials are adopted.

PMID- 27042794
TI  - Laparoscopic Modified Vecchietti Technique for Mayer-Rokitansky-Kuster-Hauser
      (MRKH) Syndrome: Report of Two Cases.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital disorder
      characterized by uterine aplasia and aplasia of the upper part of the vagina. It
      presents with primary amenorrhea in a 46, XX individual. In this paper, we report
      the cases of two patients with MRKH syndrome treated with the laparoscopic
      modified Vecchietti technique using the optimized new instruments. A neovagina
      was successfully created in these two patients. This minimally invasive technique
      offers improvements in terms of operative time, complications, and functionality.

PMID- 27042795
TI  - Abdominal Wall Endometriosis Excision with Mesh Closure - Report of Two Cases.
AB  - Abdominal wall endometriosis (AWE) is a rare condition included in the
      differential diagnosis of an abdominal wall mass and/or pelvic pain in women of
      reproductive age. It usually occurs after pelvic surgery, most commonly caesarean
      section. Given the variable clinical presentation, diagnosis can be challenging
      if a high index of suspicion for AWE does not exist. Consequently, the correct
      diagnosis is often missed in the preoperative assessment. The presence of
      endometriosis in other locations can aid in the diagnosis, but other
      endometriotic lesions do not always exist. Image studies, particularly ultrasound
      and magnetic resonance imaging, can also be of help in the differential
      diagnosis. Even though new management techniques such as ultrasound-guided
      percutaneous cryoablation seem to be promising, surgical excision is still the
      mainstay of treatment. When the aponeurosis is involved, lesion excision might
      need to be followed by wall closure with the use of a mesh to lessen tissue
      tension. We present two typical cases of AWE after caesarean section, one of them
      recurrent, in patients with concurrent endometriosis of other locations. Total
      lesion excision followed by polypropylene mesh closure has been performed, with
      very good post-operative outcomes. We aim to raise awareness towards this
      diagnosis and to highlight the importance of complete lesion excision and
      adequate closure of the abdominal wall. 

PMID- 27042796
TI  - Hybrid Coronary Revascularization: An Attractive Alternative Between Actual
      Results and Future Trends.
AB  - Optimal revascularization strategy in patients with multi-vessel coronary artery
      disease remains a matter of debate, with advantages and disadvantages in both
      surgical and percutaneous procedures. A combined approach to achieve coronary
      revascularization, termed "hybrid coronary revascularization" (HCR), has been
      recently introduced in clinical practice. HCR is defined as a scheduled
      combination of surgical left internal mammary artery to left anterior descending
      (LIMA-LAD) grafting and percutaneous treatment of at least one non-LAD coronary
      arteries, with both procedures planned and performed within a defined time limit.
      HCR is indicated in case of both proximal LAD disease eligible to surgical LIMA
      LAD grafting and non-LAD disease amenable to percutaneous procedures. Reviews and
      metanalysis of the literature showed that HCR is non-inferior to conventional
      surgical myocardial revascularization, and in case of high-risk patients, HCR can
      be the ideal option. However, the various technical approaches and time-related
      steps need to be further evaluated. Present and future research in interventional
      cardiology and cardiac surgery will turn into parallel improvements in HCR
      procedures. Surgical revascularization with off-pump techniques and minimally
      invasive approaches, scoring systems such as SYNTAX II, tools evaluating the
      hemodynamic significance of atherosclerotic plaques with physiology-based
      approaches such as fractional flow reserve and instantaneous wave-free ratio,
      newer generation drug eluting stents, newer antiplatelet agents, and therapies
      might improve indications and clinical outcomes after HCR procedures. This
      article reviews the current literature on HCR and aims to provide an overview
      about future developments. 

PMID- 27042797
TI  - Exercise in Pregnancy: First Trimester Risks.
AB  - Most national guidelines recommend moderate exercise during pregnancy, but this
      is not followed by the majority of pregnant women. Fear of exercise risks is
      among reported barriers. In contrast to most reviews focusing on late pregnancy
      risks, this review evaluates the association between exercise in the first
      trimester and the risk of miscarriage. A systematic review based on the EMBASE
      and PUBMED databases was conducted and 5 studies assessing the association
      between early pregnancy exercise and miscarriage were identified. Diverging
      findings were reported making no clear conclusion possible. New studies with
      participants included in the prepregnancy period are needed. 

PMID- 27042798
TI  - Maternal Responses to Aerobic Exercise in Pregnancy.
AB  - Exercise is one of the most physiologically challenging stressors requiring the
      coordination of metabolic, respiratory, and cardiovascular responses to meet
      increased energy requirements of the working muscle. During pregnancy, all women
      without contraindication are encouraged to exercise as part of a healthy
      lifestyle. Pregnancy itself is associated with profound physiological adaptations
      to the maternal cardiovascular, respiratory, and metabolic systems, which serve
      to support the needs of the growing fetus. Therefore the physiological
      adaptations to exercise during pregnancy are more pronounced and critically
      important. This review provides an overview of our current understanding of the
      physiological adaptations to acute prenatal exercise. 

PMID- 27042799
TI  - Measuring the Cervical Length.
AB  - An important step toward the goal of eradicating spontaneous preterm birth was
      achieved with the advent of cervical sonography, a tool that advanced our
      knowledge of the entity of preterm parturition, improved our ability to detect
      women at risk for early delivery, and allowed us to prevent some of these
      premature births. We will describe here the correct technique for obtaining such
      measurements and will review the literature regarding the use of this tool in
      specific pregnant populations. 

PMID- 27042801
TI  - Reconciling the conflicts between mitochondrial DNA haplogroup trees of Canis
      lupus.

PMID- 27042800
TI  - Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A
      paradigm shift in therapeutic approach.
AB  - BACKGROUND: The contemporary treatment of oropharyngeal squamous cell carcinoma
      (SCC) is an area of debate. We report outcomes of a minimally invasive approach
      involving transoral laser microsurgery (TLM). METHODS: A consecutive series of
      patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013
      was studied. Human papillomavirus (HPV) status was determined by p16
      immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival
      analyses were evaluated using Kaplan-Meier statistics. RESULTS: Tumor subsites
      included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n
      = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC)
      stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year
      overall survival (OS), disease-specific survival (DSS), and disease-free survival
      (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended
      favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was
      1.3%. CONCLUSION: To the best of our knowledge, this is the largest single-center
      TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative
      radiotherapy (PORT) results in at least as good oncologic outcomes as
      chemoradiotherapy (CRT), while conferring swallowing function advantages. (c)
      2016 Wiley Periodicals, Inc. Head Neck , 2016 (c) 2016 Wiley Periodicals, Inc.
      Head Neck 38:1263-1270, 2016.

PMID- 27042802
TI  - Monte Carlo dosimetric parameter study of a new (32)P brachytherapy source.
AB  - OBJECTIVE: Recently, a new catheter-based (32)P brachytherapy source has been
      developed (College of Chemistry, Sichuan University) for use in high-dose-rate
      afterloader. This study presents the results of the dosimetric data of the Geant4
      Monte Carlo (MC) simulation toolkit for this new (32)P brachytherapy source.
      METHODS: The new (32)P source had dimensions of 0.50-cm length and 0.08-cm
      diameter and was encapsulated in teflon. In this study, we attempted to obtain
      dosimetric data for this new source, as required by the formalism proposed by the
      American Association of Physicists in Medicine reports TG60 and TG149. The source
      was located in a 30-cm radius theoretical sphere water phantom, and the absorbed
      dose of the source was calculated using MC code. RESULTS: The dosimetric data
      included the reference absorbed dose rate, the radial dose function in the range
      of 0.10-0.50 cm at a longitudinal axis, the polynomial function for the radial
      dose function and the anisotropy function with a theta value of 0-90 degrees  in
      5 degrees  intervals and an r of 0.10-0.35 cm in 0.01-cm intervals. The radial
      and axial dose profiles and away-along quality assurance table are also
      calculated for the unsheathed (32)P source. The dose rate D(r0,theta0) at the
      reference point for the unsheathed (32)P source is determined to be equal to
      1.2660 +/- 0.0006 cGy s(-1) mCi. The radial dose function of the new (32)P source
      shows good agreement with the other (32)P source presented in this work with an
      average difference of 1.78%. CONCLUSION: Dosimetric data are provided for the new
      (32)P source. These data could be used in treatment-planning systems in clinical
      practice. ADVANCES IN KNOWLEDGE: Provided a new beta-emitting brachytherapy
      source that is intended for treatment of liver cancer. A dosimetric study of the
      unsheathed (32)P source for which no published dosimetric data existed was
      performed.

PMID- 27042803
TI  - Hepatobiliary and Pancreatic: Ectopic pregnancy in the liver: another rare cause
      of space occupying lesion.

PMID- 27042804
TI  - Alemtuzumab and Multiple Sclerosis: Another Note of Caution.

PMID- 27042805
TI  - Stage-specific Dietary Factors Associated with the Correa Multistep and
      Multifactorial Process of Human Gastric Carcinogenesis.
AB  - We assessed how individual dietary intakes act at different points in the chain
      of sequential stage of the Correa model in an area of Taiwan with high incidence
      of gastric cancer (GC). Using data on 2,201 participants in a two-stage screening
      for gastric neoplasia with pepsinogen test, we identified 154 superficial
      gastritis (SG), 32 atrophic gastritis (AG), 117 intestinal metaplasia (IM), and
      22 GC. Effects of individual item-based and construct-based dietary variables
      aggregated by factor analysis on each stage of gastric neoplasm were assessed.
      Based on 1,211 subjects with complete information on serological test and dietary
      questionnaire, SG was associated with positive quartile trend for the intake of
      meat (trend test P = 0.0014) and the intake of fruits and leafy vegetables (trend
      test P = 0.0177), but with the negative trend for the intake of shrimp sauce
      (trend test P = 0.039). A significant positive association was noted between milk
      and AG (trend test P = 0.014) and IM (P = 0.0087). A positive association between
      seafood and IM was noted (P = 0.011). Frequent leafy vegetable intake based on
      individual item was inversely associated with GC (P = 0.0084), whereas frequent
      intake of meat showed a high positive association (P<0.001). Stage-specific
      dietary factors underpinning the Correa model were identified.

PMID- 27042806
TI  - Give it or take it: the flux of one-carbon in cancer cells.
AB  - The sequence of the human genome together with sequence similarity analyses has
      advanced the discovery of missing steps in the mitochondrial one-carbon
      metabolism pathway. That together with the revived interest in cancer metabolism
      has brought the research on one-carbon metabolism back under the spotlight. Here,
      we present a brief review of recent advances in the field of one-carbon
      metabolism, with a bias towards its relevance to cell growth and proliferation in
      human cancers. We will address the requirements of one-carbon metabolism for
      biosynthesis and the major sources to satisfy that demand. We will also discuss
      some recent discoveries indicating a role of one-carbon metabolism beyond
      biosynthesis. We conclude with a concise enumeration of some fundamental
      questions that remain unanswered.

PMID- 27042807
TI  - Development of a robust reporter-based assay for the bioactivity determination of
      anti-VEGF therapeutic antibodies.
AB  - Development of anti-VEGF based biologic agents has been a focus in cancer
      treatment for the past decades, and several anti-VEGF pharmaceuticals have been
      already approved for treatment of various medical indications especially in
      cancer. The first anti-angiogenic agent approved by FDA was bevacizumab (BVZ,
      trade name Avastin, Genentech/Roche), a humanized anti-VEGF monoclonal antibody.
      Accurate determination of bioactivity is crucial for the safety and efficacy of
      therapeutic antibodies. The current method widely used in the lot release and
      stability test for clinical trial batches of BVZ is anti-proliferation assay
      using primary human umbilical vein endothelial cells (HUVEC), which is tedious
      with high assay variations. We describe here the development and preliminary
      validation of a reporter gene assay (RGA) that is based on an HEK293 cell line
      stably expressing vascular endothelial growth factor receptor 2 (VEGFR-2), and a
      luciferase reporter under the control of nuclear factor activated T cell (NFAT)
      response elements. Our study shows this assay not only to be superior on
      precision, sensitivity and assay simplicity compared with HUVEC assay, but also
      applicable to other VEGF-targeted biotherapeutics. These results show for the
      first time that this new reporter assay, based on the VEGF-VEGFR-NFAT pathway,
      can be a viable supplement to the HUVEC assay and employed in potency
      determination of BVZ and other kinds of anti-VEGF antibody-based biotherapeutics.

PMID- 27042808
TI  - Stability behaviour of antiretroviral drugs and their combinations. 2:
      Characterization of interaction products of lamivudine and tenofovir disoproxil
      fumarate by mass and NMR spectrometry.
AB  - This study focused on drug-drug interaction behaviour among lamivudine (3TC) and
      tenofovir disoproxil fumarate (TDF), the two anti-retroviral drugs. Apart from
      pre-known degradation products of individual drugs, a total of twelve interaction
      products were detected by high performance liquid chromatography (HPLC) using a
      C18 column as the stationary phase, and methanol and ammonium formate in gradient
      mode as the mobile phase. The same HPLC method was employed for liquid
      chromatography-high resolution mass spectrometry (LC-HRMS) and liquid
      chromatography-multi stage mass spectrometry (LC-MS(n)). For the characterization
      of interaction products, stability samples were subjected to LC-HRMS, LC-MS(n)
      and online hydrogen/deuterium exchange studies. Two isomeric interaction products
      were isolated and subjected to 1D and 2D nuclear magnetic resonance (NMR)
      studies. The collated information was utilized for the characterization of all
      twelve interaction products of the two drugs. Pathway of their formation was also
      outlined. 

PMID- 27042809
TI  - Comparative Efficacy and Safety of Everolimus-Eluting Bioresorbable Scaffold
      Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Theoretically, the everolimus-eluting bioresorbable vascular scaffold
      (BVS) could eliminate stent thrombosis and improve outcomes in patients having
      percutaneous coronary intervention. PURPOSE: To estimate the incidence of stent
      thrombosis after BVS implantation and to compare the efficacy and safety of BVSs
      versus everolimus-eluting metallic stents (EESs) in adults having percutaneous
      coronary intervention. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of
      Controlled Trials, conference proceedings, and relevant Web sites from inception
      through 20 January 2016. STUDY SELECTION: 6 randomized, controlled trials and 38
      observational studies, each involving at least 40 patients with BVS implantation.
      DATA EXTRACTION: Two reviewers independently extracted study data and evaluated
      study risk of bias. DATA SYNTHESIS: The pooled incidence of definite or probable
      stent thrombosis after BVS implantation was 1.5 events per 100 patient-years
      (PYs) (95% CI, 1.2 to 2.0 events per 100 PYs) (126 events during 8508 PYs). Six
      randomized trials that directly compared BVSs with EESs showed a non
      statistically significant increased risk for stent thrombosis (odds ratio [OR],
      2.05 [CI, 0.95 to 4.43]; P = 0.067) and myocardial infarction (OR, 1.38 [CI, 0.98
      to 1.95]; P = 0.064) with BVSs. The 6 observational studies that compared BVSs
      with EESs showed increased risk for stent thrombosis (OR, 2.32 [CI, 1.06 to
      5.07]; P = 0.035) and myocardial infarction (OR, 2.09 [CI, 1.23 to 3.55]; P =
      0.007) with BVSs. The relative rates of all-cause and cardiac death,
      revascularization, and target lesion failure were similar for BVSs and EESs.
      LIMITATION: Scarce comparative data, no published data from large trials with
      long-term follow-up, and limited quality and incomplete reporting of
      observational studies. CONCLUSION: Compared with EESs, BVSs do not eliminate and
      might increase risks for stent thrombosis and myocardial infarction in adults
      having percutaneous coronary intervention. Results of large trials with long-term
      follow-up are critically needed to establish the safety or at least the
      noninferiority of BVSs compared with EESs. PRIMARY FUNDING SOURCE: None.

PMID- 27042810
TI  - Synthesis of Nanoparticle Assemblies: general discussion.

PMID- 27042811
TI  - Comments on 'Hypothesis testing for two-stage designs with over or under
      enrollment'.

PMID- 27042812
TI  - Reply to Comments.

PMID- 27042813
TI  - Variation in Quality of Urgent Health Care Provided During Commercial Virtual
      Visits.
AB  - IMPORTANCE: Commercial virtual visits are an increasingly popular model of health
      care for the management of common acute illnesses. In commercial virtual visits,
      patients access a website to be connected synchronously-via videoconference,
      telephone, or webchat-to a physician with whom they have no prior relationship.
      To date, whether the care delivered through those websites is similar or quality
      varies among the sites has not been assessed. OBJECTIVE: To assess the variation
      in the quality of urgent health care among virtual visit companies. DESIGN,
      SETTING, AND PARTICIPANTS: This audit study used 67 trained standardized patients
      who presented to commercial virtual visit companies with the following 6 common
      acute illnesses: ankle pain, streptococcal pharyngitis, viral pharyngitis, acute
      rhinosinusitis, low back pain, and recurrent female urinary tract infection. The
      8 commercial virtual visit websites with the highest web traffic were selected
      for audit, for a total of 599 visits. Data were collected from May 1, 2013, to
      July 30, 2014, and analyzed from July 1, 2014, to September 1, 2015. MAIN
      OUTCOMES AND MEASURES: Completeness of histories and physical examinations, the
      correct diagnosis (vs an incorrect or no diagnosis), and adherence to guidelines
      of key management decisions. RESULTS: Sixty-seven standardized patients completed
      599 commercial virtual visits during the study period. Histories and physical
      examinations were complete in 417 visits (69.6%; 95% CI, 67.7%-71.6%); diagnoses
      were correctly named in 458 visits (76.5%; 95% CI, 72.9%-79.9%), and key
      management decisions were adherent to guidelines in 325 visits (54.3%; 95% CI,
      50.2%-58.3%). Rates of guideline-adherent care ranged from 206 visits (34.4%) to
      396 visits (66.1%) across the 8 websites. Variation across websites was
      significantly greater for viral pharyngitis and acute rhinosinusitis (adjusted
      rates, 12.8% to 82.1%) than for streptococcal pharyngitis and low back pain
      (adjusted rates, 74.6% to 96.5%) or ankle pain and recurrent urinary tract
      infection (adjusted rates, 3.4% to 40.4%). No statistically significant variation
      in guideline adherence by mode of communication (videoconference vs telephone vs
      webchat) was found. CONCLUSIONS AND RELEVANCE: Significant variation in quality
      was found among companies providing virtual visits for management of common acute
      illnesses. More variation was found in performance for some conditions than for
      others, but no variation by mode of communication.

PMID- 27042814
TI  - Physiology of free will.
AB  - Free will is a perception that people have that they choose to make their
      movements. This perception includes a sense of willing the movement and self
      agency that they are responsible for the movement. If there is a "free will
      force" that plays a role in movement selection, it should precede movement. There
      is no evidence for a driving force, and the perception of willing is not fully
      processed until after the movement. The perceptions of free will likely arise
      from an interaction between frontal and parietal areas. Free will might be
      considered to exist if a person's brain is functioning normally without coercion.
      Ann Neurol 2016;80:5-12.

PMID- 27042815
TI  - Sedimentation equilibria in polydisperse ferrofluids: critical comparisons
      between experiment, theory, and computer simulation.
AB  - The sedimentation equilibrium of dipolar particles in a ferrofluid is studied
      using experiment, theory, and computer simulation. A theory of the particle
      concentration profile in a dipolar hard-sphere fluid is developed, based on the
      local-density approximation and accurate expressions from a recently introduced
      logarithmic free energy approach. The theory is tested critically against Monte
      Carlo simulation results for monodisperse and bidisperse dipolar hard-sphere
      fluids in homogeneous gravitational fields. In the monodisperse case, the theory
      is very accurate over broad ranges of gravitational field strength, volume
      fraction, and dipolar coupling constant. In the bidisperse case, with realistic
      dipolar coupling constants and compositions, the theory is excellent at low
      volume fraction, but is slightly inaccurate at high volume fraction in that it
      does not capture a maximum in the small-particle concentration profile seen in
      simulations. Possible reasons for this are put forward. Experimental measurements
      of the magnetic-susceptibility profile in a real ferrofluid are then analysed
      using the theory. The concentration profile is linked to the susceptibility
      profile using the second-order modified mean-field theory. It is shown that the
      experimental results are not consistent with the sample being monodisperse. By
      introducing polydispersity in the simplest possible way, namely by assuming the
      system is a binary mixture, almost perfect agreement between theory and
      experiment is achieved.

PMID- 27042816
TI  - Nonsegmental vitiligo disease duration and female sex are associated with
      comorbidity and disease extent: a retrospective analysis in 1307 patients aged >=
      50 years.

PMID- 27042817
TI  - Dynamically scaled phantom phase contrast MRI compared to true-scale
      computational modeling of coronary artery flow.
AB  - PURPOSE: To examine the feasibility of combining computational fluid dynamics
      (CFD) and dynamically scaled phantom phase-contrast magnetic resonance imaging
      (PC-MRI) for coronary flow assessment. MATERIALS AND METHODS: Left main coronary
      bifurcations segmented from computed tomography with bifurcation angles of 33
      degrees , 68 degrees , and 117 degrees  were scaled-up ~7* and 3D printed. Steady
      coronary flow was reproduced in these phantoms using the principle of dynamic
      similarity to preserve the true-scale Reynolds number, using blood analog fluid
      and a pump circuit in a 3T MRI scanner. After PC-MRI acquisition, the data were
      segmented and coregistered to CFD simulations of identical, but true-scale
      geometries. Velocities at the inlet region were extracted from the PC-MRI to
      define the CFD inlet boundary condition. RESULTS: The PC-MRI and CFD flow data
      agreed well, and comparison showed: 1) small velocity magnitude discrepancies (2
      8%); 2) with a Spearman's rank correlation >=0.72; and 3) a velocity vector
      correlation (including direction) of r(2) >= 0.82. The highest agreement was
      achieved for high velocity regions with discrepancies being located in slow or
      recirculating zones with low MRI signal-to-noise ratio (SNRv ) in tortuous
      segments and large bifurcating vessels. CONCLUSION: Characterization of coronary
      flow using a dynamically scaled PC-MRI phantom flow is feasible and provides
      higher resolution than current in vivo or true-scale in vitro methods, and may be
      used to provide boundary conditions for true-scale CFD simulations. J. MAGN.
      RESON. IMAGING 2016;44:983-992.

PMID- 27042818
TI  - The current state of pediatric hospital medicine fellowships: A survey of program
      directors.
AB  - BACKGROUND: Pediatric hospital medicine (PHM) fellowship programs have grown
      rapidly over the last 20 years and have varied in duration and content. In an
      effort to standardize training in the absence of a single accrediting body, PHM
      fellowship directors now meet annually to discuss strategies for standardizing
      and enhancing training. OBJECTIVES: To explore similarities and differences in
      curricular structure among PHM fellowship programs in an effort to inform future
      curriculum standardization efforts. METHODS: An electronic survey was distributed
      by e-mail to all PHM fellowship directors in April 2014. The survey consisted of
      30 multiple-choice and short-answer questions focused on various curricular
      aspects of training developed by the authors. RESULTS: Twenty-seven of 31
      fellowship programs (87%) responded to the survey. Duration of most programs was
      2 years (63%), with 6, 1-year programs (22%) and 4 (15%) 3-year programs making
      up the remainder. The average amount of clinical time among programs was 50%
      (range approximately 20%-65%). In addition to general inpatient pediatric service
      time, most programs require other clinical rotations. The majority of programs
      allow fellows to bill independently for their services. Most programs offer
      certificate courses, courses for credit or noncredit courses, with 11 programs
      offering masters' degrees. Twenty-one (81%) programs provide a scholarship
      oversight committee for their fellows. Current fellows' primary areas of research
      are varied. CONCLUSION: Though variability exists regarding program length,
      clinical composition, and nonclinical offerings, several common themes emerged
      that may help inform the development of a standard curriculum for use across all
      programs. This information provides a useful starting point if pediatric hospital
      medicine obtains formal subspecialty status. Journal of Hospital Medicine
      2016;11:324-328. (c) 2016 Society of Hospital Medicine.

PMID- 27042819
TI  - Calcium hydroxide nanoparticles from solvothermal reaction for the
      deacidification of degraded waterlogged wood.
AB  - HYPOTHESIS: A combination of acid and iron ions inside the wood has been
      corroding the cellulose matrix of the Swedish warship Vasa, imposing its
      deacidification. Past deacidification treatments displayed poor penetration
      inside the wood matrix with limited efficacy. A vacuum assisted treatment of wood
      using newly developed calcium hydroxide nanoparticle dispersions represents a
      possible candidate for the treatment of acidic waterlogged wood objects such as
      sculptures and decorative artifacts. EXPERIMENTS: A solvothermal process was used
      for the synthesis of calcium hydroxide nanoparticle dispersions. Before the
      application on waterlogged wood, the physico-chemical characterization of these
      systems was carried out using several techniques. The efficacy of the
      deacidification treatment of wood samples from the Vasa was assessed by
      determination of pH and Differential Thermal Gravimetric (DTG) measurements.
      FINDINGS: The proposed solvothermal reactions can be used to produce stable and
      highly concentrated calcium hydroxide nanoparticle dispersions in alcohols,
      needing no further purification before the application. This process has also the
      advantage to be upscalable to industrial level. Both pH and DTG measurements
      showed that the newly developed dispersions can homogenously penetrate inside the
      wood up to 20cm, neutralizing acidity and creating an alkaline buffer inside the
      wooden matrix, to hinder the degradation of residual cellulose.

PMID- 27042820
TI  - A comparative study on the capacity of a range of food-grade particles to form
      stable O/W and W/O Pickering emulsions.
AB  - Whilst literature describing edible Pickering emulsions is becoming increasingly
      available, current understanding of these systems still suffers from a lack of
      consistency in terms of the (processing and formulation) conditions within which
      these structures have been studied. The current study aims to provide a
      comparative analysis of the behaviour of different edible Pickering candidates
      and their ability to stabilise emulsion droplets, under well-controlled and
      uniform experimental conditions, in order to clearly identify the particle
      properties necessary for successful Pickering functionality. More specifically,
      an extensive investigation into the suitability of various food-grade material to
      act as Pickering particles and provide stable oil-in-water (O/W) and water-in-oil
      (W/O) emulsions was carried out. Polysaccharide and flavonoid particles were
      characterised in terms of their size, zeta-potential, interfacial activity and
      wettability, under equivalent conditions. Particles were subsequently used to
      stabilise 20% w/w O/W and W/O emulsions, in the absence of added surfactant or
      other known emulsifying agents, through different processing routes. All formed
      Pickering emulsions were shown to resist significant droplet size variation and
      remain stable at particle concentrations between 2 and 3% w/w. The main particle
      prerequisites for successful Pickering stabilisation were: particle size (200nm -
      1MUm); an affinity for the emulsion continuous phase and a sufficient particle
      charge to extend stability. Depending upon the employed emulsification process,
      the resulting emulsion formation and stability behaviour can be reasonably
      predicted a priori from the evaluation of specific particle characteristics. 

PMID- 27042821
TI  - Supercapacitive properties of nanoporous oxide layer formed on 304 type stainless
      steel.
AB  - The nanoporous oxide layer is formed on the surface of 304 type stainless steel
      (SS) by chemical oxidation method. The characterization of the oxide layer is
      carried out using X-ray photoelectron spectroscopy (XPS), field-emission scanning
      electron microscopy (FE-SEM), atomic force microscopy (AFM), contact angle and
      energy-dispersive X-ray spectroscopy (EDS) techniques. The supercapacitive
      properties of oxide layer are studied using cyclic voltammetry, galvanostatic
      charge-discharge and electrochemical impedance spectroscopy techniques. 

PMID- 27042822
TI  - An evaluation of complementary approaches to elucidate fundamental interfacial
      phenomena driving adhesion of energetic materials.
AB  - Cohesive Hamaker constants of solid materials are measured via optical and
      dielectric properties (i.e., Lifshitz theory), inverse gas chromatography (IGC),
      and contact angle measurements. To date, however, a comparison across these
      measurement techniques for common energetic materials has not been reported. This
      has been due to the inability of the community to produce samples of energetic
      materials that are readily compatible with contact angle measurements. Here we
      overcome this limitation by using physical vapor deposition to produce thin films
      of five common energetic materials, and the contact angle measurement approach is
      applied to estimate the cohesive Hamaker constants and surface energy components
      of the materials. The cohesive Hamaker constants range from 85zJ to 135zJ across
      the different films. When these Hamaker constants are compared to prior work
      using Lifshitz theory and nonpolar probe IGC, the relative magnitudes can be
      ordered as follows: contact angle>Lifshitz>IGC. Furthermore, the dispersive
      surface energy components estimated here are in good agreement with those
      estimated by IGC. Due to these results, researchers and technologists will now
      have access to a comprehensive database of adhesion constants which describe the
      behavior of these energetic materials over a range of settings. 

PMID- 27042823
TI  - Effects of intermediate wettability on entry capillary pressure in angular pores.
AB  - Entry capillary pressure is one of the most important factors controlling
      drainage and remobilization of the capillary-trapped phases as it is the limiting
      factor against the two-phase displacement. It is known that the entry capillary
      pressure is rate dependent such that the inertia forces would enhance entry of
      the non-wetting phase into the pores. More importantly the entry capillary
      pressure is wettability dependent. However, while the movement of a meniscus into
      a strongly water-wet pore is well-defined, the invasion of a meniscus into a weak
      or intermediate water-wet pore especially in the case of angular pores is
      ambiguous. In this study using OpenFOAM software, high-resolution direct two
      phase flow simulations of movement of a meniscus in a single capillary channel
      are performed. Interface dynamics in angular pores under drainage conditions have
      been simulated under constant flow rate boundary condition at different
      wettability conditions. Our results shows that the relation between the half
      corner angle of pores and contact angle controls the temporal evolution of
      capillary pressure during the invasion of a pore. By deviating from pure water
      wet conditions, a dip in the temporal evolution of capillary pressure can be
      observed which will be pronounced in irregular angular cross sections. That
      enhances the pore invasion with a smaller differential pressure. The interplay
      between the contact angle and pore geometry can have significant implications for
      enhanced remobilization of ganglia in intermediate contact angles in real porous
      media morphologies, where pores are very heterogeneous with small shape factors. 

PMID- 27042824
TI  - Correction: Environmental DNA as a 'Snapshot' of Fish Distribution: A Case Study
      of Japanese Jack Mackerel in Maizuru Bay, Sea of Japan.

PMID- 27042825
TI  - HEK293T Cells Are Heterozygous for CCR5 Delta 32 Mutation.
AB  - C-C chemokine receptor 5 (CCR5) is a receptor for chemokines and a co-receptor
      for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of
      function mutation, resistant to HIV-1 infection. We tried to induce the CCR5
      delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered
      Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated
      protein 9, Cas9) in the commonly used cell line human embryonic kidney HEK 293T
      cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta
      32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia
      cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This
      finding indicates that at least one human cell line is heterozygous for the CCR5
      delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA
      and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel
      electrophoresis. 

PMID- 27042826
TI  - Inactivation of CYLD in intestinal epithelial cells exacerbates colitis
      associated colorectal carcinogenesis - a short report.
AB  - PURPOSE: CYLD is a tumor suppressor that has been linked to the development of
      various human malignancies, including colon cancer. The tumor-suppressing
      function of CYLD is associated with its deubiquitinating activity, which maps to
      the carboxyl-terminal region of the protein. In the present study we evaluated
      the role of intestinal epithelial CYLD in colitis-associated cancer using a
      conditional mouse CYLD inactivation model. METHODS: In order to evaluate the role
      of CYLD in intestinal epithelial carcinogenesis, mice (IEC-Cyld (Delta9) mice)
      that carry a mutation that eliminates the deubiquitinating domain of CYLD in
      intestinal epithelial cells (IEC) were generated by crossing Villin-Cre
      transgenic mice to previously generated mice carrying a loxP-flanked Cyld exon 9
      (Cyld (flx9) mice). RESULTS: We found that IEC-Cyld (Delta9) mice did not present
      spontaneous intestinal abnormalities up to one year of age. However, upon
      challenge with a combination of genotoxic (AOM) and pro-inflammatory (DSS) agents
      we found that the number of adenomas in the IEC-Cyld (Delta9) mice was
      dramatically increased compared to the control mice. Inactivation of CYLD in
      intestinal epithelial cells did not affect the classical nuclear factor-kappaB
      (NF-kappaB) and c-Jun kinase (JNK) activation pathways under physiological
      conditions, suggesting that these pathways do not predispose CYLD-deficient
      intestinal epithelia to colorectal cancer development before the onset of
      genotoxic and/or pro-inflammatory stress. CONCLUSIONS: Our findings underscore a
      critical tumor-suppressing role for functional intestinal epithelial CYLD in
      colitis-associated carcinogenesis. CYLD expression and its associated pathways in
      intestinal tumors may be exploited for future prognostic and therapeutic
      purposes.

PMID- 27042827
TI  - TNF-alpha promotes breast cancer cell migration and enhances the concentration of
      membrane-associated proteases in lipid rafts.
AB  - PURPOSE: Tumor progression is associated with cell migration, invasion and
      metastasis. These processes are accompanied by the activation of specific
      proteases that are either linked to cellular membranes or are secreted into
      extracellular spaces. TNF-alpha is known to play an important role in various
      aspects of tumor progression. The aim of this work was to assess the effect of
      TNF-alpha on the migration of breast cancer cells and, in addition, to assess its
      association with the location of membrane-associated proteases in lipid rafts.
      METHODS: Wound scratch healing and Transwell migration assays were used to study
      the effect of TNF-alpha on the migration of both hormone-dependent and hormone
      independent breast cancer-derived cells, i.e., MCF7 and MDA-MB-231, respectively.
      The expression and secretion of three matrix metalloproteases, MMP9, MMP2 and MT1
      MMP, and two dipeptidyl peptidases, CD26 and FAP-alpha, was investigated using RT
      PCR, Western blotting and gelatin zymography. In addition, activation of the
      MAPK/ERK signaling pathway was investigated by Western blotting. RESULTS: We
      found that a TNF-alpha-induced enhancement of breast cancer cell migration was
      accompanied by an increased secretion of MMP9, but not MMP2, into the culture
      media. We also found that TNF-alpha upregulated the expression of the dipeptidyl
      peptidases CD26 and FAP-alpha in a dose-dependent manner and, in addition,
      enhanced the concentration of all five proteases in lipid rafts in the breast
      cancer-derived cells tested, regardless of cell type. Furthermore, we found that
      TNF-alpha activated the MAPK/ERK signaling pathway by increasing the ERK1/2
      phosphorylation level. Application of the MEK/ERK1/2 inhibitor U-0126 resulted in
      down-regulation of TNF-alpha-induced MMP9 secretion and abrogation of the
      enhanced concentration of proteases in the lipid rafts. CONCLUSIONS: From our
      results we conclude that TNF-alpha-induced activation of the MAPK/ERK signaling
      pathway may promote breast cancer cell migration via both upregulation of MMP9,
      CD26 and FAP-alpha and concentration of these proteases, as also MT1-MMP and
      MMP2, in the lipid rafts. TNF-alpha may serve as a potential therapeutic target
      in breast cancers susceptible to TNF-alpha stimulation.

PMID- 27042828
TI  - Influence of Salt Intake on Association of Blood Uric Acid with Hypertension and
      Related Cardiovascular Risk.
AB  - BACKGROUND: A relationship of blood uric acid (UA) with hypertension and
      cardiovascular risk is under debate thus salt intake is hypothesized to
      contribute to such associations. METHODS: In this cross-sectional study,
      stratified cluster random sampling elicited a sample of 1805 Kazakhs with 92.4%
      compliance. Hypertension and moderate-or-high total cardiovascular risk (mTCR)
      were defined according to guidelines. Sodium intake was assessed by urinary
      sodium excretion. Prevalence ratios (PRs) were used to express associations of UA
      with hypertension and mTCR. RESULTS: In the highest tertile of sodium intake in
      women, the adjusted PRs (95% confidence intervals) of low to high quartiles
      compared with the lowest quartile of UA, were 1.22(0.78-1.91), 1.18(0.75-1.85),
      and 1.65(1.09-2.51) for hypertension and 1.19(0.74-1.90), 1.39(0.91-2.11), and
      1.65(1.10-2.47) for mTCR (P for trend <0.05). However, these findings were not
      shown for other sodium intake levels. There were similar results in men. PRs
      markedly increased with a concomitant increase in UA and sodium intake and there
      was a significant interaction (P = 0.010) for mTCR with PRs of 1.69(1.10-2.60)
      for men and 3.70(2.09-6.52) for women in those with the highest compared with the
      lowest quartile of UA and tertile of sodium intake. Similar findings were shown
      for hypertension. CONCLUSIONS: This study implied that a high salt intake may
      enhance the associations of UA with hypertension and cardiovascular risk.

PMID- 27042829
TI  - Intake of Meat Proteins Substantially Increased the Relative Abundance of Genus
      Lactobacillus in Rat Feces.
AB  - Diet has been shown to have a critical influence on gut bacteria and host health,
      and high levels of red meat in diet have been shown to increase colonic DNA
      damage and thus be harmful to gut health. However, previous studies focused more
      on the effects of meat than of meat proteins. In order to investigate whether
      intake of meat proteins affects the composition and metabolic activities of gut
      microbiota, feces were collected from growing rats that were fed with either meat
      proteins (from beef, pork or fish) or non-meat proteins (casein or soy) for 14
      days. The resulting composition of gut microbiota was profiled by sequencing the
      V4-V5 region of the 16S ribosomal RNA genes and the short chain fatty acids
      (SCFAs) were analyzed using gas chromatography. The composition of gut microbiota
      and SCFA levels were significantly different between the five diet groups. At a
      recommended dose of 20% protein in the diet, meat protein-fed rats had a higher
      relative abundance of the beneficial genus Lactobacillus, but lower levels of
      SCFAs and SCFA-producing bacteria including Fusobacterium, Bacteroides and
      Prevotella, compared with the soy protein-fed group. Further work is needed on
      the regulatory pathways linking dietary protein intake to gut microbiota. 

PMID- 27042830
TI  - Determinant factors of physical fitness in European children.
AB  - OBJECTIVES: This study was designed to explore the determinants of physical
      fitness in European children aged 6-11 years, cross-sectionally and
      longitudinally. METHODS: There were sufficient data on 4903 children (50.6 %
      girls) on measured physical fitness (cardio-respiratory, muscular strength,
      flexibility, balance, and speed) and possible determinants related to child
      characteristics, child lifestyle and parental factors. Multivariate and mixed
      linear regression models were conducted. RESULTS: Age, sex, children's BMI and
      physical activity were independent and strong determinants of children's fitness.
      Significant but small effects were found for low maternal BMI, high psychosocial
      well-being and fruit and vegetable intake as protective determinants. Sleep
      duration, breakfast intake, parental age and education and paternal BMI did not
      have a consistently significant effect on physical fitness. The role of
      determinants depended on children's sex and the specific PF component.
      Longitudinal analyses especially highlighted the importance of child's BMI as
      physical fitness determinant, independent of physical activity. CONCLUSIONS: BMI
      together with physical activity, diet and psychosocial factors are modifiable
      targets to enhance physical fitness. This calls for policy approaches that
      combine these factors in a systematic way.

PMID- 27042831
TI  - Social/economic costs and health-related quality of life in patients with
      histiocytosis in Europe.
AB  - OBJECTIVE: The aim of this study was to determine the economic burden from a
      societal perspective and the health-related quality of life (HRQOL) of patients
      with histiocytosis in Europe. METHODS: We conducted a cross-sectional study of
      patients with histiocytosis from France, Germany, Italy, Spain, Bulgaria, the UK,
      and Sweden. Data on demographic characteristics, health resource utilisation,
      informal care, loss of labour productivity and HRQOL were collected from the
      questionnaires completed by patients or their caregivers. HRQOL was measured with
      the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: A total of 134 patients (35
      France, 32 Germany, 30 Italy, 24 Spain, 7 Bulgaria, 4 UK and 2 Sweden) completed
      the questionnaire. The average annual costs ranged from ? 6832 to ? 33,283
      between countries, the year of reference being 2012. Estimated direct healthcare
      costs ranged from ? 1698 to ? 18,213; direct nonhealthcare costs ranged from ?
      2936 to ? 17,622 and labour productivity losses ranged from ? 1 to ? 8855. The
      mean EQ-5D score for adult histiocytosis patients was estimated at between 0.32
      and 0.85, and the mean EQ-5D visual analogue scale score was estimated at between
      50.00 and 66.50. CONCLUSION: The main strengths of this study lie in our bottom
      up approach to costing and in the evaluation of histiocytosis patients from a
      broad perspective (societal costs). This type of analysis is very scarce in
      international literature for rare diseases in comparison with other illnesses. We
      conclude that histiocytosis patients incur considerable societal costs and
      experience substantial deterioration in HRQOL.

PMID- 27042833
TI  - Evaluation of EPI-X4 as a urinary peptide biomarker for diagnosis and prognosis
      of late acute GvHD.

PMID- 27042832
TI  - Critically ill allogeneic hematopoietic stem cell transplantation patients in the
      intensive care unit: reappraisal of actual prognosis.
AB  - The outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      patients has significantly improved over the past decade. Still, a significant
      number of patients require intensive care unit (ICU) management because of life
      threatening complications. Literature from the 1990s reported extremely poor
      prognosis for critically ill allo-HSCT patients requiring ICU management. Recent
      data justify the use of ICU resources in hematologic patients. Yet, allo-HSCT
      remains an independent variable associated with mortality. However, outcomes in
      allo-HSCT patients have improved over time and many classic determinants of
      mortality have become irrelevant. The main actual prognostic factors are the need
      for mechanical ventilation, the presence of GvHD and the number of organ failures
      at ICU admission. Recently, the development of reduced-intensity conditioning
      regimens, early ICU admission and the increased use of noninvasive ventilation,
      combined with time effect and general advances in hematology, in allo-HSCT
      procedures and in ICU management have contributed to improve general outcome. A
      rational policy of ICU admission triage in these patients is very hard to define,
      as each decision for ICU admission is a case-by-case decision at patient bedside.
      The collaboration between hematologists and intensivists is crucial in this
      context. 

PMID- 27042834
TI  - Development, preliminary usability and accuracy testing of the EBMT 'eGVHD App'
      to support GvHD assessment according to NIH criteria-a proof of concept.
AB  - The EBMT Complications and Quality of Life Working Party has developed a computer
      based algorithm, the 'eGVHD App', using a user-centered design process. Accuracy
      was tested using a quasi-experimental crossover design with four expert-reviewed
      case vignettes in a convenience sample of 28 clinical professionals. Perceived
      usefulness was evaluated by the technology acceptance model (TAM) and User
      satisfaction by the Post-Study System Usability Questionnaire (PSSUQ). User
      experience was positive, with a median of 6 TAM points (interquartile range: 1)
      and beneficial median total, and subscale PSSUQ scores. The initial standard
      practice assessment of the vignettes yielded 65% correct results for diagnosis
      and 45% for scoring. The 'eGVHD App' significantly increased diagnostic and
      scoring accuracy to 93% (+28%) and 88% (+43%), respectively (both P<0.05). The
      same trend was observed in the repeated analysis of case 2: accuracy improved by
      using the App (+31% for diagnosis and +39% for scoring), whereas performance
      tended to decrease once the App was taken away. The 'eGVHD App' could
      dramatically improve the quality of care and research as it increased the
      performance of the whole user group by about 30% at the first assessment and
      showed a trend for improvement of individual performance on repeated case
      evaluation. 

PMID- 27042835
TI  - Highly favorable outcome in BRCA-mutated metastatic breast cancer patients
      receiving high-dose chemotherapy and autologous hematopoietic stem cell
      transplantation.
AB  - Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging
      agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic
      breast cancer (MBC) patients receiving high-dose chemotherapy and autologous
      hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA
      wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA
      untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut
      Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt)
      patients were identified from our institutional genetic database. Overall
      survival (OS) was the primary end point. A total of 235 patients were included.
      In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate
      analyses, the BRCA(mut) status was an independent prognostic factor for OS
      (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and
      PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC
      receiving HDC AHSCT, we report a highly favorable survival outcome in the subset
      of patients with documented germline BRCA mutations.

PMID- 27042836
TI  - Blood glucose control using a computer-guided glucose management system in
      allogeneic hematopoietic cell transplant recipients.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative
      treatment for patients with hematological malignancies. However, is associated
      with substantial rates of morbidity and mortality. We and others have shown that
      malglycemia is associated with adverse transplant outcome. Therefore, improving
      glycemic control may improve transplant outcome. In this prospective study we
      evaluated the feasibility of using Glucommander (a Computer-Guided Glucose
      Management System; CGGM) in order to achieve improved glucose control in
      hospitalized HCT patients. Nineteen adult patients contributed 21 separate
      instances on CGGM. Patients were on CGGM for a median of 43 h. Median initial
      blood glucose (BG) on CGGM was 244 mg/dL, and patients on 20 study instances
      reached the study BG target of 100-140 mg/dL after a median of 6 h. After BG
      reached the target range, the median average BG level per patient was 124 mg/dL.
      Six patients had a total of 10 events of BG <70 mg/dL (0.9% of BG measurements),
      and no patients experienced BG level <40 mg/dL. The total estimated duration of
      BG <70 mg/dL was 3 h (0.2% of the total CGGM time). In conclusion, our study
      demonstrates that stringent BG control in HCT patients using CGGM is feasible. 

PMID- 27042837
TI  - Multi-color immune-phenotyping of CD34 subsets reveals unexpected differences
      between various stem cell sources.
AB  - Flow cytometric routine CD34 analysis enumerates hematopoietic stem and
      progenitor cells irrespective of their subpopulations although this might predict
      engraftment dynamics and immune reconstitution. We established a multi-color CD34
      assay containing CD133, CD45RA, CD10, CD38 and CD33. We examined PBSC, donor bone
      marrow (BMd) and BM of patients 1 year after allografting (BM1y) regarding their
      CD34 subset composition, which differed significantly amongst those materials:
      the early CD45RA(-)CD133(+)CD38(low) subpopulations were significantly more
      frequent in PBSC than in BMd, and very low in BM1y. Vice versa, clearly more
      committed CD34 stages prevailed in BM, particularly in BM1y where the proportion
      of multi-lymphoid and CD38(++) B-lymphoid precursors was highest (mean 59%). CD33
      was expressed at different intensity on CD45RA(+/-)CD133(+/-) subsets allowing
      discrimination of earlier from more committed myeloid precursors. Compared with
      conventional CD34(+) cell enumeration, the presented multi-color phenotyping is a
      qualitative approach defining different CD34 subtypes in any CD34 source. Its
      potential impact to predict engraftment kinetics and immune reconstitution has to
      be evaluated in future studies. 

PMID- 27042838
TI  - Pharmacokinetics and immunological outcomes of alemtuzumab-based treatment for
      steroid-refractory acute GvHD.

PMID- 27042839
TI  - Hematopoietic cell transplantation in older adults: deciding or decision-making?

PMID- 27042840
TI  - Assessment of tumoral plasma cells in apheresis products for autologous stem cell
      transplantation in multiple myeloma.

PMID- 27042841
TI  - Italian consensus conference for the outpatient autologous stem cell
      transplantation management in multiple myeloma.
AB  - Multiple myeloma (MM) is the leading indication for autologous stem cell
      transplantation (ASCT) worldwide. The safety and efficacy of reducing hospital
      stay for MM patients undergoing ASCT have been widely explored, and different
      outpatient models have been proposed. However, there is no agreement on the
      criteria for selecting patients eligible for this strategy as well as the
      standards for their clinical management. On the basis of this rationale, the
      Italian Group for Stem Cell Transplantation (GITMO) endorsed a project to develop
      guidelines for the management of outpatient ASCT in MM, using evidence-based
      knowledge and consensus-formation techniques. An expert panel convened to discuss
      the currently available data on the practice of outpatient ASCT management and
      formulated recommendations according to the supporting evidence. Evidence gaps
      were filled with consensus-based statements. Three main topics were addressed:
      (1) the identification of criteria for selecting MM patients eligible for
      outpatient ASCT management; (2) the definition of standard procedures for
      performing outpatient ASCT (model, supportive care and monitoring during the
      aplastic phase); (3) the definition of the standard criteria and procedures for
      re-hospitalization during the aplastic phase at home. Herein, we report the
      summary and the results of the discussion and the consensus. 

PMID- 27042842
TI  - Autologous stem cell transplantation for patients aged 60 years or older with
      refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis
      from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM
      TC).
AB  - This report retrospectively analyzed the outcome of 91 patients aged 60 years or
      older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who
      underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and
      were reported to the French Society of Bone Marrow Transplantation and Cell
      Therapies registry. The median age at transplant was 63 years. The majority of
      patients exhibited disease chemosensitivity to salvage treatment (57 complete
      responses, 30 partial responses, 1 progressive disease and 3 unknown). The most
      frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan
      (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates
      of overall survival (OS) and progression free survival (PFS) for the entire group
      were 67 and 54%, respectively. Despite the missing data, in univariate analysis,
      the number of salvage chemotherapy lines (1-2 versus ?3) significantly influenced
      the OS, unlike the other prognostic factors (stage III-IV at relapse, disease
      status before ASCT and negative positron emission tomography (PET) scan)
      encountered in younger patients. In spite of its limitations, this retrospective
      study with a long-term follow-up suggests that ASCT is a valid treatment option
      for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate
      of toxicity. 

PMID- 27042843
TI  - Factors influencing the late phase of recovery after bone mineral density loss in
      allogeneic stem cell transplantation survivors.
AB  - Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem
      cell transplantation (SCT) and is related to factors such as steroids and chronic
      GvHD. In order to understand the natural history of BMDL of SCT in the longer
      term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up
      of 12 years (range 3-22 years). All women received hormone replacement therapy,
      and routine calcium/vitamin D supplementation was recommended but ~50% of
      patients still had suboptimal vitamin D levels and bisphosphonates were rarely
      utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and
      forearm remained vulnerable sites. Younger age, higher pretransplant body mass
      index (BMI) and increment in BMI post transplant were significantly associated
      with increased BMD and protected against osteopenia/osteoporosis. These findings
      support consideration of BMD loss in SCT survivors in two phases, an early phase
      of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different
      protective and aggravating factors. Treatment- and transplant-related factors
      (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to
      impact the early phase of BMD loss but age and BMI are more influential in the
      late phase of BMD recovery. 

PMID- 27042844
TI  - Long-term follow-up of (90)Y-ibritumomab-tiuxetan ((90)YIT) in the conditioning
      of autologous hematopoietic transplantation for indolent and mantle cell
      lymphomas in a single French center.

PMID- 27042845
TI  - Evolution of serum cytokine profile after hematopoietic stem cell transplantation
      in systemic sclerosis patients.

PMID- 27042846
TI  - Longer delay of hematological recovery and increased transfusion needs after
      haploidentical compared to non-haploidentical stem cell transplantation.

PMID- 27042847
TI  - Impact of early CMV reactivation in cord blood stem cell recipients in the
      current era.
AB  - Several studies have reported an association between CMV reactivation and a
      decreased incidence of relapse for AML after adult donor allogeneic hematopoietic
      cell transplantation (HCT). Limited data, however, are available on the impact of
      CMV reactivation on relapse after cord blood (CB) stem cell transplantation. The
      unique combination of higher incidence of CMV reactivation in the seropositive
      recipient and lower incidence of graft versus host disease (GvHD) in CB HCT
      permits a valuable design to analyze the impact of CMV reactivation. Data from
      1684 patients transplanted with CB between 2003 and 2010 for AML and ALL were
      analyzed. The median time to CMV reactivation was 34 days (range: 2-287). CMV
      reactivation and positive CMV serology were associated with increased non-relapse
      mortality (NRM) among both AML and ALL CB recipients (reactivation, AML: relative
      risk (RR) 1.41 (1.07-1.85); ALL: 1.60 (1.14-2.23); Serology, AML: RR 1.39 (1.05
      1.85), ALL: RR 1.61 (1.18-2.19)). For patients with ALL, but not those with AML,
      this yielded inferior overall survival (P<0.005). Risk of relapse was not
      influenced by CMV reactivation or positive CMV serostatus for either disease. 

PMID- 27042849
TI  - Predictive value of high EVI1 expression in AML patients undergoing myeloablative
      allogeneic hematopoietic stem cell transplantation in first CR.
AB  - The EVI1 gene is a transcriptional regulator of hematopoietic stem cell self
      renewal and its overexpression is associated with adverse prognosis in de novo
      AML. Whether the overexpression of EVI1 also predicts poor outcome of AML
      patients undergoing myeloablative allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) in first CR (CR1) is still unclear. Thirty-two
      (21.2%) out of 151 patients were categorized as high EVI1 expression (EVI1+), and
      119 (78.8%) patients were categorized as low EVI1 expression (EVI1-). The
      frequency of EVI1+ was much higher in the adverse-risk group than the
      intermediate-risk group (53% vs 19%, P=0.005). EVI1+ patients were significantly
      likely to harbor with translocations involving the MLL gene on 11q23 (8/9).
      Significantly poor results were observed in the EVI1+ cohort in terms of leukemia
      free survival (LFS) (in 24 months 52.6 vs 71.0%, P=0.027), overall survival (OS)
      (in 24 months 52.8 vs 72.4%, P=0.012), and cumulative incidence of relapse (in 24
      months 39.5 vs 22.5%, P=0.013). Multivariable analysis revealed that low EVI1
      expression as an independent prognostic factor favoring LFS (hazards ratio=0.47,
      95% confidence interval 0.26-0.86, P=0.01) but not OS. Our results indicate high
      EVI1 expression might predict high risk of relapse in AML patients undergoing
      myeloablative allo-HSCT in CR1. 

PMID- 27042848
TI  - How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic
      HSCT.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients
      frequently develop glucose intolerance and post-transplant diabetes mellitus
      (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT
      outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute
      to the development of PTDM. Here we review information about hyperglycemia and
      PTDM after allo-HSCT as well as PTDM after solid organ transplantation and
      describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into
      consideration a lack of well-established evidence in the field of allo-HSCT, more
      studies should be conducted in the future, which will require closer
      multidisciplinary collaboration between hematologists, endocrinologists and
      nutritionists. 

PMID- 27042850
TI  - Busulfan-melphalan in high-risk neuroblastoma: the 30-year experience of a single
      institution.
AB  - High-dose chemotherapy (HDC) was investigated in high-risk neuroblastoma (HR-NBL)
      to reduce the risk of relapse. We report the results of the 30-year experience of
      a cohort of patients with HR-NBL treated with high-dose (HD) busulfan (Bu)
      containing regimens. From 1980 to 2009, 215 patients aged >1 year with stage 4
      NBL were treated with HD Bu-containing regimens at Gustave Roussy. These data
      were prospectively recorded in the Pediatric Transplantation Database. The median
      age at diagnosis was 40 months (12-218 months). All patients had a stage 4
      neuroblastoma. NMYC amplification was displayed in 24% of the tumors. The
      hematopoietic support consisted of bone marrow or PBSCs in 46% and 49% of
      patients, respectively. The 5-year event-free survival and overall survival rates
      of the whole cohort were 35.1% and 40%, respectively. Age at diagnosis, bone
      marrow involvement and tumor response after induction chemotherapy were
      significant prognostic factors. Toxicity was manageable and decreased over time,
      owing to both PBSC administration and better supportive care. Based on this
      experience, HD Bu-melphalan (Mel) has been implemented in Europe and compared
      with Carboplatin-Etoposide-Mel in the European SIOP Neuroblastoma (SIOPEN)/HR-NBL
      randomized protocol. It has now become the standard HDC in the SIOPEN HR
      strategy. 

PMID- 27042851
TI  - Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory
      infections.
AB  - Adoptive immunotherapy with transplant donor-derived virus-specific T cells has
      emerged as a potentially curative approach for the treatment of drug-refractory
      EBV+lymphomas as well as CMV and adenovirus infections complicating allogeneic
      hematopoietic cell transplants. Adoptive transfer of HLA partially matched virus
      specific T cells from healthy third party donors has also shown promise in the
      treatment of these conditions, with disease response rates of 50-76% and
      strikingly low incidences of toxicity or GVHD recorded in initial trials. In this
      review, we examine the reported experience with transplant donor and third party
      donor-derived virus-specific T cells, identifying characteristics of the viral
      pathogen, the T cells administered and the diseased host that contribute to
      treatment response or failure. We also describe the characteristics of virus
      specific T-cell lines in our center's bank and the frequency with which in vitro
      culture promotes expansion of immunodominant T cells specific for epitopes that
      are presented by a limited array of prevalent HLA alleles, which facilitates
      their broad applicability for treatment. 

PMID- 27042853
TI  - Feasibility and Outcome of a Brief Cognitive Behaviour Therapy Family
      Intervention for Patients with Obsessive-Compulsive Disorder: A Pilot Study.

PMID- 27042852
TI  - Targeting persistent androgen receptor signaling in castration-resistant prostate
      cancer.
AB  - Castration-resistant prostate cancer (CRPC), the invariably lethal phenotype of
      advanced prostate cancer, represents a clinical state defined by disease
      progression despite reduction of testosterone to castrate levels (i.e., <=50
      ng/dL). Although resistant to androgen-deprivation therapy (i.e., LHRH
      agonists/antagonists), CRPC continues to depend on the androgen receptor (AR)
      signaling pathway. Supporting the importance of AR-signaling in a castration
      resistant state, the next-generation AR-signaling inhibitors enzalutamide and
      abiraterone have been shown to afford a survival benefit in men with metastatic
      CRPC. However, primary and secondary resistance mechanisms to these agents
      inevitably drive continued disease progression-often as a result of re-activation
      of AR-signaling. With increased understanding of the mechanisms underlying how
      continued AR-signaling occurs in spite of drugs like abiraterone and
      enzalutamide, a new wave of therapies is emerging designed to more effectively
      target AR-signaling. This review will focus on the more clinically relevant
      mechanisms of CRPC drug resistance and our ongoing efforts to develop drugs to
      target these mechanisms. 

PMID- 27042854
TI  - Mice with a Mutation in the Mdm2 Gene That Interferes with MDM2/Ribosomal Protein
      Binding Develop a Defect in Erythropoiesis.
AB  - MDM2, an E3 ubiquitin ligase, is an important negative regulator of tumor
      suppressor p53. In turn the Mdm2 gene is a transcriptional target of p53, forming
      a negative feedback loop that is important in cell cycle control. It has recently
      become apparent that the ubiquitination of p53 by MDM2 can be inhibited when
      certain ribosomal proteins, including RPL5 and RPL11, bind to MDM2. This
      inhibition, and the resulting increase in p53 levels has been proposed to be
      responsible for the red cell aplasia seen in Diamond-Blackfan anemia (DBA) and in
      5q- myelodysplastic syndrome (MDS). DBA and 5q- MDS are associated with inherited
      (DBA) or acquired (5q- MDS) haploinsufficiency of ribosomal proteins. A mutation
      in Mdm2 causing a C305F amino acid substitution blocks the binding of ribosomal
      proteins. Mice harboring this mutation (Mdm2C305F), retain a normal p53 response
      to DNA damage, but lack the p53 response to perturbations in ribosome biogenesis.
      While studying the interaction between RP haploinsufficiency and the Mdm2C305F
      mutation we noticed that Mdm2C305F homozygous mice had altered hematopoiesis.
      These mice developed a mild macrocytic anemia with reticulocytosis. In the bone
      marrow (BM), these mice showed a significant decrease in Ter119hi cells compared
      to wild type (WT) littermates, while no decrease in the number of mature
      erythroid cells (Ter119hiCD71low) was found in the spleen, which showed
      compensated bone marrow hematopoiesis. In methylcellulose cultures, BFU-E
      colonies from the mutant mice were slightly reduced in number and there was a
      significant reduction in CFU-E colony numbers in mutant mice compared with WT
      controls (p < 0.01). This erythropoietic defect was abrogated by concomitant p53
      deficiency (Trp53ko/ko). Further investigation revealed that in Mdm2C305F
      animals, there was a decrease in Lin-Sca-1+c-Kit+ (LSK) cells, accompanied by
      significant decreases in multipotent progenitor (MPP) cells (p < 0.01).
      Competitive BM repopulation experiments showed that donor BM harboring the
      Mdm2C305F mutation possessed decreased repopulation capacity compared to WT BM,
      suggesting a functional stem cell deficit. These results suggest that there is a
      fine tuned balance in the interaction of ribosomal proteins with the MDM2/p53
      axis which is important in normal hematopoiesis. 

PMID- 27042855
TI  - Clinical Relevance of IgE to Profilin and/or Polcalcin in Pollen-Sensitized
      Patients.
AB  - BACKGROUND: Component-resolved diagnostics is gaining importance in allergy
      diagnostics. Allergen extracts contain components with different rates of
      prevalence and clinical relevance, which can be subdivided at molecular level
      into major and minor allergens. Clinical complaints are usually triggered by
      major allergens, while the role of sensitization to the panallergens profilin and
      polcalcin still remains unclear. METHODS: Eighty-six patients from southern
      Bavaria with sensitization to the panallergens profilin (Bet v 2/Phl p 12) and/or
      polcalcin (Bet v 4/Phl p 7) were examined in regard to their sensitization to the
      4 main botanic denominations Betulaceae, Oleaceae, Poaceae and Asteraceae by skin
      prick test and measurement of specific immunoglobulin E antibodies to natural
      allergen extracts as well as major allergen components rPhl p 1/5, rBet v 1, rOle
      e 1 and nArt v 1. Sensitization was rated as clinically relevant or irrelevant
      depending on anamnesis or intranasal allergen challenge. RESULTS: Regarding the 4
      botanic denominations, there was no significant difference in the incidence of
      sensitization to the panallergens profilin, polcalcin or both. The sensitization
      pattern does not alter when subdividing the cohort into clinically relevant and
      silent sensitization. We did not find clinically symptomatic sensitization to
      panallergens without cosensitization to a major allergen. CONCLUSIONS: Our
      results suggest that sole sensitization to panallergens seems to have no clinical
      relevance in allergic rhinoconjunctivitis. Clinical complaints seem to be
      triggered manly by major allergens. Thus, component-resolved allergy diagnostics
      is crucial in the diagnosis and treatment of polysensitized patients.

PMID- 27042856
TI  - Identification of Epigenetic Biomarkers of Lung Adenocarcinoma through Multi
      Omics Data Analysis.
AB  - Epigenetic mechanisms such as DNA methylation or histone modifications are
      essential for the regulation of gene expression and development of tissues.
      Alteration of epigenetic modifications can be used as an epigenetic biomarker for
      diagnosis and as promising targets for epigenetic therapy. A recent study
      explored cancer-cell specific epigenetic biomarkers by examining different types
      of epigenetic modifications simultaneously. However, it was based on microarrays
      and reported biomarkers that were also present in normal cells at a low
      frequency. Here, we first analyzed multi-omics data (including ChIP-Seq data of
      six types of histone modifications: H3K27ac, H3K4me1, H3K9me3, H3K36me3,
      H3K27me3, and H3K4me3) obtained from 26 lung adenocarcinoma cell lines and a
      normal cell line. We identified six genes with both H3K27ac and H3K4me3 histone
      modifications in their promoter regions, which were not present in the normal
      cell line, but present in >=85% (22 out of 26) and <=96% (25 out of 26) of the
      lung adenocarcinoma cell lines. Of these genes, NUP210 (encoding a main component
      of the nuclear pore complex) was the only gene in which the two modifications
      were not detected in another normal cell line. RNA-Seq analysis revealed that
      NUP210 was aberrantly overexpressed among the 26 lung adenocarcinoma cell lines,
      although the frequency of NUP210 overexpression was lower (19.3%) in 57 lung
      adenocarcinoma tissue samples studied and stored in another database. This study
      provides a basis to discover epigenetic biomarkers highly specific to a certain
      cancer, based on multi-omics data at the cell population level. 

PMID- 27042857
TI  - Analysis of a single-codon E746 deletion in exon 19 of the epidermal growth
      factor receptor.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) gene mutations are the most
      established genomic biomarkers for the efficacy of EGFR tyrosine kinase
      inhibitors (EGFR-TKIs). The most frequent deletion in exon 19 is delE746_750,
      followed by del747_753insS and del747_750insP. Since investigations of delE746
      have not been reported previously, it is unclear if delE746 conveys sensitivity
      to TKI effect of TKI on EGFR delE746. The objective was to characterize delE746
      of the EGFR gene and to explore the effects of TKIs on the delE746. METHODS: We
      assessed the ability of gefitinib to inhibit phosphorylation of clonal L929 cell
      lines expressing EGFR with delE746. 3-D structures of the EGFR proteins were also
      used to investigate the interaction with gefitinib. RESULTS: The delE746 mutant
      EGFR-expressing cells exhibited gefitinib-sensitive autophosphorylation, which
      altered the structure of the EGFR and increased the instances of docking during
      docking simulations of gefitinib with the EGFR-TK. This mutant revealed that it
      exhibited molecular conformation alterations, and more frequent binding with
      gefitinib compared to wild-type EGFR. We administered EGFR-TKI, gefitinib to a
      Japanese woman with lung cancer that contained delE746. The patient achieved
      partial response after a 5 month of treatment with gefitinib. CONCLUSION: Our
      study revealed biological, structural, and probably clinical features of the
      delE746 form of EGFR.

PMID- 27042858
TI  - Salivary Melatonin in Relation to Depressive Symptom Severity in Young Adults.
AB  - Reduced levels of melatonin have been associated with severe depression. The aim
      was to investigate the correlation between salivary melatonin and dimensional
      measures of depressive symptom severity in young adult psychiatric patients.
      Levels of melatonin were analyzed in six saliva samples during waking hours from
      119 young adult patients under outpatient psychiatric care. Melatonin levels were
      tested for association with the severity of depressive symptoms using the self
      rating version of the Montgomery Asberg Depression Rating Scale (MADRS-S). Where
      possible, depressive symptoms were assessed again after 6+/-2 months of
      treatment. Response was defined as decrease in MADRS-S by >=50% between baseline
      and follow-up. Patients with levels of melatonin in the lowest quartile at
      bedtime had an increased probability of a high MADRS-S score compared to those
      with the highest levels of melatonin (odds ratio 1.39, 95% CI 1.15-1.69, p<0.01).
      A post hoc regression analysis found that bedtime melatonin levels predicted
      response (odds ratio 4.4, 95% CI 1.06-18.43, p<0.05). A negative relationship
      between salivary melatonin and dimensional measures of depressive symptom
      severity was found in young patients under outpatient psychiatric care. Bedtime
      salivary melatonin levels may have prognostic implications. 

PMID- 27042859
TI  - Moral Disengagement as Mediator and Moderator of the Relation Between Empathy and
      Aggression Among Chinese Male Juvenile Delinquents.
AB  - The link between empathy and aggression is well documented; yet, studies
      examining potential mechanisms that explain this association are limited. In the
      present study, we tested the relation between empathy and aggression and examined
      both the mediating and moderating effects of moral disengagement on this relation
      among Chinese male juvenile delinquents. Three hundred and fifty-seven male
      juvenile delinquents from one Chinese juvenile correctional facility completed
      the interpersonal reactivity index, the moral disengagement scale and the
      aggression questionnaire. The results indicated that moral disengagement
      partially mediated the influence of empathy on aggression. Moreover, moral
      disengagement moderated the relation between empathy and aggression.
      Specifically, there was a significant negative relation between empathy and
      aggression at low levels of moral disengagement. However, at high levels of moral
      disengagement, the relation between empathy and aggression was non-significant.
      The significance and limitations of the results are discussed.

PMID- 27042860
TI  - Layer-by-Layer Deposition with Polymers Containing Nitrilotriacetate, A
      Convenient Route to Fabricate Metal- and Protein-Binding Films.
AB  - This paper describes a convenient synthesis of nitrilotriacetate (NTA)-containing
      polymers and subsequent layer-by-layer adsorption of these polymers on flat
      surfaces and in membrane pores. The resulting films form NTA-metal-ion complexes
      and capture 2-3 mmol of metal ions per mL of film. Moreover, these coatings bind
      multilayers of polyhistidine-tagged proteins through association with NTA-metal
      ion complexes. Inclusion of acrylic acid repeat units in NTA-containing
      copolymers promotes swelling to increase protein binding in films on Au-coated
      wafers. Adsorption of NTA-containing films in porous nylon membranes gives
      materials that capture ~46 mg of His-tagged ubiquitin per mL. However, the
      binding capacity decreases with the protein molecular weight. Due to the high
      affinity of NTA for metal ions, the modified membranes show modest leaching of
      Ni(2+) in binding and rinsing buffers. Adsorption of NTA-containing polymers is a
      simple method to create metal- and protein-binding films and may, with future
      enhancement of stability, facilitate development of disposable membranes that
      rapidly purify tagged proteins.

PMID- 27042861
TI  - Memristive Switching in Bi(1-x)Sb(x) Nanowires.
AB  - We investigated the memristive switching behavior in bismuth-antimony alloy (Bi(1
      x)Sb(x)) single nanowire devices at 0.1 <= x <= 0.42. At 0.15 <= x <= 0.42, most
      Bi(1-x)Sb(x) single nanowire devices exhibited bipolar resistive switching (RS)
      behavior with on/off ratios of approximately 10(4) and narrow variations in
      switching parameters. Moreover, the resistance values in the low-resistance state
      (LRS) were insensitive to x. On the other hand, at 0.1 <= x <= 0.15, some Bi(1
      x)Sb(x) single nanowire devices showed complementary RS-like behavior, which was
      ascribed to asymmetric contact properties. Transmission electron microscopy and
      elemental mapping images of Bi, Sb, and O obtained from the cross sections of the
      Bi(1-x)Sb(x) single nanowire devices, which were cut before and after RS,
      revealed that the mobile species was Sb ions, and the migration of the Sb ions to
      the nanowire surface brought the switch to LRS. In addition, we demonstrated that
      two types of synaptic plasticity, namely, short-term plasticity and long-term
      potentiation, could be implemented in Bi(1-x)Sb(x) nanowires by applying a
      sequence of voltage pulses with different repetition intervals.

PMID- 27042862
TI  - MARTINI Coarse-Grained Model of Triton TX-100 in Pure DPPC Monolayer and Bilayer
      Interfaces.
AB  - The coarse-grained MARTINI model of Triton TX-100 has been validated by direct
      comparison of the experimental and calculated area increase in pure DPPC lipid
      bilayers and monolayers at water/air interfaces in the presence of surfactant and
      by comparison of electron density profiles calculated with more detailed
      atomistic models based on the CHARMM force field. Bilayer simulations have been
      performed and compared with monolayers and with atomistic models. The validated
      CG model has been employed to study the phase separation of TX-100 molecules in
      lipid bilayers and the effect of the lipid bilayer curvature.

PMID- 27042863
TI  - Spin-State Tuning at Pseudo-tetrahedral d(6) Ions: Spin Crossover in [BP3]Fe(II)
      X Complexes.
AB  - Low-coordinate transition-metal complexes that undergo spin crossover remain
      rare. We report here a series of four-coordinate, pseudo-tetrahedral P3FeII-X
      complexes supported by tris(phosphine)borate P3 ([PhBP3R]-) and phosphiniminato X
      type ligands (-N?PR3') that, in combination, tune the spin-crossover behavior of
      the system. Most of the reported iron complexes undergo spin crossover at
      temperatures near or above room temperature in solution and in the solid state.
      The change in spin state coincides with a significant change in the degree of pi
      bonding between Fe and the bound N atom of the phosphiniminato ligand. Spin
      crossover is accompanied by striking changes in the ultraviolet-visible (UV-vis)
      absorption spectra, which allows for quantitative modeling of the thermodynamic
      parameters of the spin equilibria. These spin equilibria have also been studied
      by numerous techniques including paramagnetic nuclear magnetic resonance (NMR),
      infrared, and Mossbauer spectroscopies; X-ray crystallography; and solid-state
      superconducting quantum interference device (SQUID) magnetometry. These studies
      allow qualitative correlations to be made between the steric and electronic
      properties of the ligand substituents and the enthalpy and entropy changes
      associated with the spin equilibria.

PMID- 27042865
TI  - Strong Modulation of Optical Properties in Black Phosphorus through Strain
      Engineered Rippling.
AB  - Controlling the bandgap through local-strain engineering is an exciting avenue
      for tailoring optoelectronic materials. Two-dimensional crystals are particularly
      suited for this purpose because they can withstand unprecedented nonhomogeneous
      deformations before rupture; one can literally bend them and fold them up almost
      like a piece of paper. Here, we study multilayer black phosphorus sheets
      subjected to periodic stress to modulate their optoelectronic properties. We find
      a remarkable shift of the optical absorption band-edge of up to ~0.7 eV between
      the regions under tensile and compressive stress, greatly exceeding the strain
      tunability reported for transition metal dichalcogenides. This observation is
      supported by theoretical models that also predict that this periodic stress
      modulation can yield to quantum confinement of carriers at low temperatures. The
      possibility of generating large strain-induced variations in the local density of
      charge carriers opens the door for a variety of applications including
      photovoltaics, quantum optics, and two-dimensional optoelectronic devices.

PMID- 27042866
TI  - Axially Chiral Bifunctional 8,8'-Biquinolyl: Synthesis of 7,7'-Dihydroxymethyl
      8,8'-biquinolyl via Pd-Catalyzed Double C-H Oxidation of 7,7'-Dimethyl-8,8'
      biquinolyl.
AB  - Bifunctional C2-symmetric 7,7'-dihydroxymethyl-8,8'-biquinolyl (2) was
      synthesized in short steps via (i) Cu/Pd-catalyzed homo coupling of 7-methyl-8
      bromoquinoline and (ii) Pd(II)-catalyzed double C-H oxidation. Axial chirality of
      2 and its synthetic precursor 7,7'-dimethyl-8,8'-biquinolyl (3) is stable.
      Optically active 2 was obtained through separation of racemic 2 by chiral column
      HPLC or Pd(II)-catalyzed double C-H oxidation of optically active 3. The absolute
      stereochemistry of enantiomers of 2 and 3 was determined using the exciton
      chirality method.

PMID- 27042864
TI  - Enantioselective CuH-Catalyzed Hydroallylation of Vinylarenes.
AB  - The enantioselective, intermolecular hydroallylation of vinylarenes employing
      allylic phosphate electrophiles has been achieved through a copper hydride
      catalyzed process. The protocol described herein can be applied to a diverse set
      of vinylarene substrates and allows for the installation of the parent allyl
      group as well as a range of 2-substituted allylic fragments. 

PMID- 27042867
TI  - In-Depth Proteomic Quantification of Cell Secretome in Serum-Containing
      Conditioned Medium.
AB  - Secreted proteins play key roles during cellular communication, proliferation,
      and migration. The comprehensive profiling of secreted proteins in serum
      containing culture media is technically challenging. Most studies have been
      performed under serum-free conditions. However, these conditions might alter the
      status of the cells. Herein, we describe an efficient strategy that avoids the
      disturbance of serum by combining metabolic labeling, protein "equalization,"
      protein fractionation, and filter-aided sample preparation, called MLEFF,
      enabling the identification of 534 secreted proteins from HeLa conditioned media,
      including 31 cytokines, and growth factors. This MLEFF strategy was also
      successfully applied during a comparative secretome analysis of two human
      hepatocellular carcinoma cell lines with differentially metastatic potentials,
      enabling the quantification of 61 significantly changed proteins involved in
      tumor invasion and metastasis.

PMID- 27042868
TI  - ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical
      outcomes.
AB  - ITI-007 is an investigational drug being developed for schizophrenia and other
      neuropsychiatric/neurodegenerative diseases. ITI-007 has a unique pharmacological
      profile, combining potent 5-HT2a receptor antagonism with cell-type-specific
      dopamine and glutamate receptor modulation, plus serotonin reuptake inhibition.
      At dopamine-D2 receptors, ITI-007 acts as a post-synaptic antagonist and pre
      synaptic partial agonist. Additionally, ITI-007 stimulates phosphorylation of
      glutamatergic NMDA-NR2B receptors, downstream of dopamine-D1 receptor
      intracellular signaling. Based on a large, placebo and risperidone controlled,
      Phase-II trial, ITI-007 60 mg was shown to be effective in reducing symptoms in
      patients with acutely exacerbated schizophrenia. The antipsychotic efficacy of
      ITI-007 60 mg in this patient population was confirmed in a recently completed
      Phase III study. ITI-007 was associated with minimal safety risk compared to
      risperidone (Phase II study) or placebo (both studies) for neuromotor
      disturbances, prolactin changes, weight gain and metabolic abnormalities. A
      second 6-week, placebo and risperidone-controlled Phase-III trial in acutely
      exacerbated schizophrenia is ongoing.

PMID- 27042869
TI  - Different Dimensions: Internalized Homonegativity Among African American Men Who
      Have Sex With Men in the Deep South.
AB  - This study examined the psychometric properties of the Internalized
      Homonegativity Inventory (IHNI) among African American men who have sex with men
      (AAMSM) in the southeastern United States. Data from 261 AAMSM were analyzed
      using exploratory factor analysis. Results showed evidence of a two-factor
      solution: personal and moral homonegativity and gay affirmation. Internal
      consistencies were greater than .80, and correlations with other variables (e.g.,
      sociodemographics, religiosity, masculinity) provided evidence of validity.
      Findings suggesting a two-factor instead of a three-factor solution may indicate
      that the IHNI manifests differently for AAMSM in the Deep South than for
      predominantly White MSM. Further research should examine how incorporating new
      conceptions of internalized homonegativity into culturally specific health
      promotion interventions for AAMSM might enhance effectiveness.

PMID- 27042870
TI  - The Circle to Publication: Focus on Authors' Survey.

PMID- 27042871
TI  - Mesothelial Cysts of the Round Ligament of the Uterus in 9 Patients: a 15-year
      experience.
AB  - Aim of this study was to evaluate the characteristic features of patients with
      mesothelial cyst of the round ligament of the uterus and the incidence of this
      entity. This was a retrospective review of 3065 patients who underwent inguinal
      exploration for groin mass from 1998 to 2013. Clinical, radiological and
      histopathological features of patients with a diagnosis of mesothelial cyst of
      the round ligament were analyzed. Of the 405 female patients reviewed 9
      mesothelial cysts of the round ligament were identified (2.2%). The median age
      was 37 (range 19-82 years). In all patients the groin mass was manually
      irreducible on physical examination. The lesions were on the right side in 6
      (66.6%) patients. These were identified before surgery in 4 (all by groin
      ultrasonography). Three were misidentified as a hernia before surgery. The
      remaining 2 (22%) had both hernia and the mesothelial cyst of the round ligament.
      The cysts were identified after surgery at the time of histopathological
      examination in these two patients. In all patients histopathological examination
      revealed multilobular cystic lesion lined by a single layer of mesothelial cells.
      Cystic lesions arising from the round ligament were identified and excised along
      with the round ligament in 7 patients. In the remaining 2, a hernia repair was
      also performed. There was no recurrence at follow-up. Mesothelial cysts of the
      round ligament are rare. They are easily misidentified as groin hernia. An
      accurate diagnosis requires a high index of suspicion and is greatly aided by
      preoperative imaging studies.

PMID- 27042872
TI  - Psychometric Analysis of the Three-Factor Eating Questionnaire-R18V2 in
      Adolescent and Young Adult-Aged Central Nervous System Tumor Survivors.
AB  - PURPOSE: Adolescent and young adult (AYA)-aged central nervous system (CNS) tumor
      survivors are an understudied population that is at risk of developing adverse
      health outcomes, such as obesity. Long-term follow-up guidelines recommend
      monitoring those at risk of obesity, thus motivating the need for an eating
      behavior questionnaire. An abbreviated online version of the Three-Factor Eating
      Questionnaire (TFEQ-R18v2) has been developed, but its applicability to this
      population is not yet known. This study investigated the instrument's factor
      structure and reliability in this population. METHODS: AYA-aged CNS tumor
      survivors (n = 114) aged 15-39 years completed the TFEQ-R18V2 questionnaire
      online. Confirmatory factor analysis was used to examine the fit of the three
      factor structure (uncontrollable eating, cognitive restraint, and emotional
      eating [EE]) and reliability (internal consistency of the TFEQ-R18v2).
      Associations between the three factors and body mass index (BMI) were assessed by
      linear regression. RESULTS: The theorized three-factor structure was supported in
      our population (RMSEA = 0.056 and CFI = 0.98) and demonstrated good reliability
      (alpha of 0.81-0.93). EE (beta = 0.07, 95% CI 0.02-0.13) was positively
      associated with BMI, whereas the other two subscale scores were not. CONCLUSION:
      The TFEQ-R18v2 instrument holds promise for research and clinical use among AYA
      aged CNS tumor survivors. The instrument may be a useful tool for researchers to
      develop tailored weight management strategies. It also may be a valuable tool for
      clinicians to monitor survivors who are at risk of obesity and to facilitate
      referral. Our results also suggest that EE in this population should be further
      investigated as a potential target for intervention.

PMID- 27042874
TI  - Out-of-Hospital Cardiac Arrest--Are Drugs Ever the Answer?

PMID- 27042873
TI  - Collagen-chitosan 3-D nano-scaffolds effects on macrophage phagocytosis and pro
      inflammatory cytokine release.
AB  - Macrophages are effector cells in the innate and adaptive immune systems and in
      situ exist within three-dimensional (3-D) microenvironments. As there has been an
      increase in interest in the use of 3-D scaffolds to mimic natural
      microenvironments in vitro, this study examined the impact on cultured mice
      peritoneal macrophages using standard 2-D plates as compared to 3-D collagen
      chitosan scaffolds. Here, 2-D and 3-D cultured macrophages were evaluated for
      responses to lipopolysaccharide (LPS), dexamethasone (Dex), BSA (bovine serum
      albumin), safranal (herbal component isolated from safranal [Saf]) and Alyssum
      homolocarpum mucilage (A. muc: mixed herbal components). After treatments,
      cultured macrophages were evaluated for viability, phagocytic activity and
      release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta pro
      inflammatory cytokines. Comparison of 2-D vs 3-D cultures showed that use of
      either system - with or without any exogenous agent - had no effect on cell
      viability. In the case of cell function, macrophages cultured on scaffolds had
      increases in phagocytic activity relative to that by cells on 2-D plates. In
      general, the test herbal components Saf and A. muc. had more impact than any of
      the other exogenous agents on nanoparticle uptake. With respect to production of
      TNFalpha and IL-1beta, compared to the 2-D cells, scaffold cells tended to have
      significantly different levels of production of each cytokine, with the effect
      varying (higher or lower) depending on the test agent used. However, unlike with
      particle uptake, here, while Saf and A. muc. led to significantly greater levels
      of cytokine formation by the 3-D culture cells vs that by the 2-D plate cells,
      there was no net effect (stimulatory) vs control cultures. These results
      illustrated that collagen-chitosan scaffolds could provide a suitable 3-D
      microenvironment for macrophage phagocytosis and could also impact on the
      formation of pro-inflammatory cytokines.

PMID- 27042875
TI  - Cigarette Smoking, BPDE-DNA Adducts, and Aberrant Promoter Methylations of Tumor
      Suppressor Genes (TSGs) in NSCLC from Chinese Population.
AB  - Non-small cell lung cancer (NSCLC) is related to the genetic and epigenetic
      factors. The goal of this study was to determine association of cigarette smoking
      and BPDE-DNA adducts with promoter methylations of several genes in NSCLC.
      Methylation of the promoters of p16, RARbeta, DAPK, MGMT, and TIMP-3 genes of
      tumor tissues from 199 lung cancer patients was analyzed with methylation
      specific PCR (MSP), and BPDE-DNA adduct level in lung cancer tissue was obtained
      by ELISA. Level of BPDE-DNA adduct increased significantly in males, aged people
      (over 60 years), and smokers; however, no significant difference was found while
      comparing the BPDE-DNA adduct levels among different tumor types, locations, and
      stages. Cigarette smoking was also associated with increased BPDE-DNA adducts
      level (OR = 2.43, p > .05) and increased methylation level in at least 1 gene (OR
      = 5.22, p < .01), both in dose-response manner. Similarly, cigarette smoking also
      significantly increase the risk of p16 or DAPK methylation (OR = 3.02, p < .05
      for p16, and 3.66, p < .05 for DAPK). The highest risk of BPDE-DNA adducts was
      detected among individuals with cigarette smoking for more than 40 pack-years (OR
      = 4.21, p < .01). Furthermore, the present study did not show that BPDE-DNA
      adducts are significantly associated with abnormal TSGs methylations in NSCLC,
      including SCC and AdO, respectively. Conclusively, cigarette smoking is
      significantly associated with the increase of BPDE-DNA adduct level, promoter
      hypermethylation of p16 and DAPK genes, while BPDE-DNA adduct was not
      significantly related to abnormal promoter hypermethylation in TSGs, suggesting
      that BPDE-DNA adducts and TSGs methylations play independent roles in NSCLC. 

PMID- 27042876
TI  - Diagnosis of human enteroviruses that cause hand, foot and mouth disease.

PMID- 27042877
TI  - Complex dynamics in biological systems arising from multiple limit cycle
      bifurcation.
AB  - In this paper, we study complex dynamical behaviour in biological systems due to
      multiple limit cycles bifurcation. We use simple epidemic and predator-prey
      models to show exact routes to new types of bistability, that is, bistability
      between equilibrium and periodic oscillation, and bistability between two
      oscillations, which may more realistically describe the real situations.
      Bifurcation theory and normal form theory are applied to investigate the multiple
      limit cycles bifurcating from Hopf critical point. 

PMID- 27042878
TI  - Patient-physician relationship in the management of asthma: Multicentric approach
      in Latin America.
AB  - OBJECTIVE: To investigate and compare how Latin American physicians rate
      themselves on the use of communication strategies in the management of asthma
      patients, and to explore their personal experience and opinions on asthma
      treatment. METHODS: A cross-sectional survey of physicians attending
      international medical conferences in Latin America was conducted. Participants
      rated themselves on frequency of use of 24 communication strategies using a 5
      point Likert scale. For statistical analysis, self-rating responses were divided
      into two classes: very likely to (always or often on a Likert scale) and not very
      likely to (sometimes, seldom or never on a Likert scale). Participants also
      answered 4 multiple choice questions about management of asthma patients. Overall
      responses were analyzed using descriptive statistics and Chi-square. Multivariate
      logistic regression analysis was performed to evaluate self-ratings by country,
      gender, practice area (GP or specialist) and age. RESULTS: A total of 304
      physicians from Ecuador, Argentina and Peru responded. Overall, the majority of
      respondents rated themselves very likely to use 21 of the 24 communication
      strategies. Some significant differences were observed in self-ratings among
      physicians from different countries, between males and females, between GPs and
      specialists and between younger and older physicians. Responses to the multiple
      choice questions showed that 79.6% of the respondents believed that most or
      almost all patients can achieve asthma control. CONCLUSIONS: A high percentage of
      the Latin American physicians surveyed rated themselves very likely to use good
      communication strategies when managing asthma patients and felt that asthma
      control can be achieved in most or almost all patients.

PMID- 27042879
TI  - Changing paradigms in the treatment of hormone-receptor positive advanced breast
      cancer.

PMID- 27042880
TI  - Face matching impairment in developmental prosopagnosia.
AB  - Developmental prosopagnosia (DP) is commonly referred to as 'face blindness', a
      term that implies a perceptual basis to the condition. However, DP presents as a
      deficit in face recognition and is diagnosed using memory-based tasks. Here, we
      test face identification ability in six people with DP, who are severely impaired
      on face memory tasks, using tasks that do not rely on memory. First, we compared
      DP to control participants on a standardized test of unfamiliar face matching
      using facial images taken on the same day and under standardized studio
      conditions (Glasgow Face Matching Test; GFMT). Scores for DP participants did not
      differ from normative accuracy scores on the GFMT. Second, we tested face
      matching performance on a test created using images that were sourced from the
      Internet and so varied substantially due to changes in viewing conditions and in
      a person's appearance (Local Heroes Test; LHT). DP participants showed
      significantly poorer matching accuracy on the LHT than control participants, for
      both unfamiliar and familiar face matching. Interestingly, this deficit is
      specific to 'match' trials, suggesting that people with DP may have particular
      difficulty in matching images of the same person that contain natural day-to-day
      variations in appearance. We discuss these results in the broader context of
      individual differences in face matching ability.

PMID- 27042881
TI  - Black and blue: Exploring racial bias and law enforcement in the killings of
      unarmed black male civilians.
AB  - In late 2014, a series of highly publicized police killings of unarmed Black male
      civilians in the United States prompted large-scale social turmoil. In the
      current review, we dissect the psychological antecedents of these killings and
      explain how the nature of police work may attract officers with distinct
      characteristics that may make them especially well-primed for negative
      interactions with Black male civilians. We use media reports to contextualize the
      precipitating events of the social unrest as we ground our explanations in theory
      and empirical research from social psychology and industrial and organizational
      (I/O) psychology. To isolate some of the key mechanisms at play, we disentangle
      racial bias (e.g., stereotyping processes) from common characteristics of law
      enforcement agents (e.g., social dominance orientation), while also addressing
      the interaction between racial bias and policing. By separating the moving parts
      of the phenomenon, we provide a more fine-grained analysis of the factors that
      may have contributed to the killings. In doing so, we endeavor to more
      effectively identify and develop solutions to eradicate excessive use of force
      during interactions between "Black" (unarmed Black male civilians) and "Blue"
      (law enforcement).

PMID- 27042882
TI  - Social (dis)order and psychosocial trauma: Look earlier, look outside, and look
      beyond the persons.
AB  - The most common and extreme suffering humankind has ever experienced comes from
      interpersonal and collective intentional violence. In dealing with traumatic
      outcomes psychology must overcome the mutually constitutive interaction between
      the (dis)order of a given macro or microsocial context and the mental health of
      the persons living in it. Social psychologist Ignacio Martin-Baro addressed in a
      preferential way the study of civil war in El Salvador in terms of intergroup
      hostility and polarization. He also approached the aftereffects of war by means
      of a theoretical core assumption: that traumatic experience rooted in collective
      violence (a human-made stressor) should be understood bearing in mind its social
      roots (pretraumatic situation), its personal and collective harm (collective
      injury), and the destruction of the social fabric. These are the arguments for
      his conceptualization of psychosocial trauma. Twenty-six years after the violent
      murder of Martin-Baro, along with 5 Jesuit priests, a housekeeper, and his
      teenage daughter, the current authors have adopted his general framework. Based
      on new theoretical insights and supporting data, the authors propose an expanded
      4-dimension theoretical argument on psychosocial trauma: (a) pretrauma conditions
      based on social distress, (b) shared network of fear leading to breakdown of core
      social assumptions, (c) the outgroup as a target of negative emotions, and (d)
      destruction of family ties and community networks.

PMID- 27042883
TI  - Quagmires for clinical psychology and executive coaching? Ethical considerations
      and practice challenges.
AB  - As the coaching field burgeons, both the mental health and coaching
      professionals, and their respective professions, face a myriad of potential
      quagmires, especially if the unique challenges encountered are ignored. After a
      short introduction and presentation on ethics and morals related to executive
      coaching and clinical therapy, a discussion follows on the lengthy and intimate
      relationship between executive coaching and psychology. Next are definitions and
      comparisons and 6 areas that are potential quagmires. This includes roles, skill
      sets/core competencies, education/training, licensing/credentialing
      certification, governing bodies and confidentiality, and fees/reimbursement. Each
      section includes a discussion and several questions to highlight potentially
      problematic areas, practice challenges, and/or ethical issues, followed with
      brief responses. This paper concludes with the inquiry, "Where do we go from
      here?"

PMID- 27042884
TI  - Replication is about effect size: Comment on Maxwell, Lau, and Howard (2015).
AB  - The view that a single study can be trusted is an attractive but false promise
      provided by null hypothesis testing. The replication question should be to what
      extent investigators can reproduce effect sizes and how narrow their 95%
      confidence interval can become. Cumulative meta-analyses will enable us to
      determine how replicable psychological effects are and what their effect size is.

PMID- 27042885
TI  - Preregister if you want to.
AB  - Prespecification of confirmatory hypothesis tests is a useful tool that makes our
      statistical tests informative. On the other hand, selectively reporting studies,
      measures, or statistical tests renders the probability of false positives higher
      than the p values would imply. The bad news is that it is usually difficult to
      tell how much higher the probability is. Fortunately, there are enormous
      opportunities to improve the quality of our science by preregistering our
      research plans. Preregistration is a highly distinctive strength that should
      increase our faith in the veracity and replicability of a research result.

PMID- 27042886
TI  - Should title lengths really adhere to the American Psychological Association's
      twelve word limit?
AB  - The publication manual for the American Psychological Association (APA) suggests
      that title lengths do not exceed 12 words, yet journals do not prevent longer
      titles. Here, we examined title lengths in APA journals to see how many exceeded
      the APA's suggested limit. First, we conducted a systematic analysis of 235
      articles in the current issues of 23 APA journals. A total of 52% of titles were
      more than 12 words long. Second, we examined articles from APA journals that were
      at least 50 years old to examine whether title lengths have changed over time.
      Our results suggested that the average title lengths have indeed increased with
      time. One of 2 courses should be taken. Perhaps science is becoming more complex
      that longer titles are needed in order to convey the primary message to the
      reader. If this is the case, then the APA's word limit should be increased. On
      the other hand, however, maybe editor and reviewers should try to enforce the
      current word limit to force writers to be succinct. Either way, editors should
      make their preferences clear so that the trend for longer titles does not
      continue unchecked.

PMID- 27042887
TI  - Karl H. Pribram (1919-2015).
AB  - Presents an obituary for Karl H. Pribram, who died on January 19, 2015. Karl had
      a very successful and extensive 70-year career in neuroscience research. He was a
      prolific researcher and writer, publishing approximately 150 data papers, almost
      300 theoretical papers, and 19 books. His work is recognized through many awards
      and titles, including a Doctorate in Psychology from the University of Montreal
      in 1992, a Doctorate in Philosophy from the University of Bremen (1996), and a
      lifetime achievement award from the International Neural Network Society. His
      professional interactions extended beyond the traditional boundaries of science
      into the arts and humanities. His work in these integrative areas resulted in his
      becoming the first recipient of the Baclav Havel Prize for integrating science
      with the humanities and arts.

PMID- 27042888
TI  - Lee B. Sechrest (1929-2015).
AB  - Presents an obituary for Lee B. Sechrest, who died after a long illness at his
      home in Tucson, Arizona, on the evening of October 10, 2015. Sechrest was a well
      known expert on research methodology, measurement, and evaluation.

PMID- 27042889
TI  - Roger Alan Myers (1930-2015).
AB  - Presents an obituary for Roger Alan Myers, who passed away September 13, 2015, in
      Stuart, Florida, at age 85. Meyers was a long-time national leader of counseling
      psychology.

PMID- 27042890
TI  - Elizabeth Scarborough (1935-2015).
AB  - Presents an obituary for Pauline Elizabeth Scarborough, who died on August 18,
      2015, at her home in Mishawaka, Indiana, after a long and well-fought battle with
      cancer. Scarborough was a historian of psychology, whose studies of late-19th-
      and early-20th-century women psychologists (often with her close friend, Laurel
      Furumoto) revolutionized our understanding of early American psychology.

PMID- 27042891
TI  - Mark Chaffin (1952-2015).
AB  - Presents an obituary for Mark Chaffin, who passed away unexpectedly on August 23,
      2015, in Atlanta, Georgia, while riding his bike on the Atlanta Beltline, a joy
      and passion for him. Mark was a leader in the field of child maltreatment
      research. He dedicated his career to helping at-risk children and families. His
      distinguished career belied his self-proclaimed, self-effacing lack of
      accomplishment.

PMID- 27042892
TI  - Proteolytic crosstalk in multi-protease networks.
AB  - Processive proteases, such as ClpXP in E. coli, are conserved enzyme assemblies
      that can recognize and rapidly degrade proteins. These proteases are used for a
      number of purposes, including degrading mistranslated proteins and controlling
      cellular stress response. However, proteolytic machinery within the cell is
      limited in capacity and can lead to a bottleneck in protein degradation, whereby
      many proteins compete ('queue') for proteolytic resources. Previous work has
      demonstrated that such queueing can lead to pronounced statistical relationships
      between different protein counts when proteins compete for a single common
      protease. However, real cells contain many different proteases, e.g. ClpXP,
      ClpAP, and Lon in E. coli, and it is not clear how competition between proteins
      for multiple classes of protease would influence the dynamics of cellular
      networks. In the present work, we theoretically demonstrate that a multi-protease
      proteolytic bottleneck can substantially couple the dynamics for both simple and
      complex (oscillatory) networks, even between substrates with substantially
      different affinities for protease. For these networks, queueing often leads to
      strong positive correlations between protein counts, and these correlations are
      strongest near the queueing theoretic point of balance. Furthermore, we find that
      the qualitative behavior of these networks depends on the relative size of the
      absolute affinity of substrate to protease compared to the cross affinity of
      substrate to protease, leading in certain regimes to priority queue statistics. 

PMID- 27042894
TI  - Long QT syndrome in isolated ventricular noncompaction.

PMID- 27042893
TI  - Young Barley Indicates Antitumor Effects in Experimental Breast Cancer In Vivo
      and In Vitro.
AB  - The effect of dietary administered young barley containing a mixture of
      phytochemicals to female rats for the prevention of N-methyl-N-nitrosourea
      induced mammary carcinogenesis was evaluated. After carcinogen administration (14
      wk), mammary tumors were removed and prepared for histopathological and
      immunohistochemical analysis. Moreover, in vitro evaluation of possible
      mechanisms in MCF-7 breast cancer cell line was performed. Barley (0.3%)
      demonstrated mild antitumor effect in mammary carcinogenesis, yet 3% barley did
      not further improve this effect. Immunohistochemical analysis of rat tumor cells
      in treated groups showed significant increase in caspase-3 expression and
      significant reduction in Ki67 expression. In addition, 3% barley significantly
      decreased dityrosine levels versus control. Barley in higher dose significantly
      decreased serum low-density lipoprotein-cholesterol in rats. In vitro studies
      showed that barley significantly decreased survival of MCF-7 cells in 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and significantly
      decreased 5-bromo-20-deoxyuridine incorporation versus control. Barley prevented
      cell cycle progression and extended incubation with barley showed significant
      increase in the percentage of annexin V/propidium iodide-positive MCF-7 cells.
      Our results propose an antitumor effect for the mixture of phytochemicals present
      in young barley in a breast cancer model.

PMID- 27042895
TI  - Transient and anatomic isolated right-ventricular hypoplasia.

PMID- 27042899
TI  - AD or Not AD? That Is Just One of the Questions.

PMID- 27042900
TI  - The Mental Status Examination in Patients With Suspected Dementia.
AB  - PURPOSE OF REVIEW: This article describes a comprehensive approach to the mental
      status examination and diagnostic workup of patients suspected of having an
      emerging neurodegenerative dementia. Key strategies for obtaining a history and
      bedside examination techniques are highlighted. RECENT FINDINGS: Classic
      descriptions of behavioral neurology syndromes were largely based on
      clinicopathologic correlations of strategic lesions in stroke patients. While
      still very important, advances in neuroimaging have expanded our armamentarium of
      cognitive evaluations to include assessments of findings in nonstroke anatomic
      distributions of disease. These efforts support comprehensive assessments of
      large-scale cerebral networks in cognitive neurology. SUMMARY: A thorough and
      focused mental status examination is essential for the evaluation of patients
      with cognitive symptoms. Selective use of laboratory testing and neuroimaging can
      aid in the diagnosis of dementia by excluding non-neurodegenerative etiologies.
      Neurodegenerative disease-specific tests are in development and will enhance
      diagnosis and efforts for disease-modifying therapy development.

PMID- 27042901
TI  - Mild Cognitive Impairment.
AB  - PURPOSE OF REVIEW: As individuals age, the quality of cognitive function becomes
      an increasingly important topic. The concept of mild cognitive impairment (MCI)
      has evolved over the past 2 decades to represent a state of cognitive function
      between that seen in normal aging and dementia. As such, it is important for
      health care providers to be aware of the condition and place it in the
      appropriate clinical context. RECENT FINDINGS: Numerous international population
      based studies have been conducted to document the frequency of MCI, estimating
      its prevalence to be between 15% and 20% in persons 60 years and older, making it
      a common condition encountered by clinicians. The annual rate in which MCI
      progresses to dementia varies between 8% and 15% per year, implying that it is an
      important condition to identify and treat. In those MCI cases destined to develop
      Alzheimer disease, biomarkers are emerging to help identify etiology and predict
      progression. However, not all MCI is due to Alzheimer disease, and identifying
      subtypes is important for possible treatment and counseling. If treatable causes
      are identified, the person with MCI might improve. SUMMARY: MCI is an important
      clinical entity to identify, and while uncertainties persist, clinicians need to
      be aware of its diagnostic features to enable them to counsel patients. MCI
      remains an active area of research as numerous randomized controlled trials are
      being conducted to develop effective treatments.

PMID- 27042902
TI  - Alzheimer Disease.
AB  - PURPOSE OF REVIEW: This article discusses the recent advances in the diagnosis
      and treatment of Alzheimer disease (AD). RECENT FINDINGS: In recent years,
      significant advances have been made in the fields of genetics, neuroimaging,
      clinical diagnosis, and staging of AD. One of the most important recent advances
      in AD is our ability to visualize amyloid pathology in the living human brain.
      The newly revised criteria for diagnosis of AD dementia embrace the use for
      biomarkers as supportive evidence for the underlying pathology. Guidelines for
      the responsible use of amyloid positron emission tomography (PET) have been
      developed, and the clinical and economic implications of amyloid PET imaging are
      actively being explored. SUMMARY: Our improved understanding of the clinical
      onset, progression, neuroimaging, pathologic features, genetics, and other risk
      factors for AD impacts the approaches to clinical diagnosis and future
      therapeutic interventions.

PMID- 27042903
TI  - Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia.
AB  - PURPOSE OF REVIEW: This article provides an overview of the clinical features,
      neuropathologic findings, diagnostic criteria, and management of dementia with
      Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the
      Lewy body dementias. RECENT FINDINGS: DLB and PDD are common, clinically similar
      syndromes that share characteristic neuropathologic changes, including deposition
      of alpha-synuclein in Lewy bodies and neurites and loss of tegmental dopamine
      cell populations and basal forebrain cholinergic populations, often with a
      variable degree of coexisting Alzheimer pathology. The clinical constellations of
      DLB and PDD include progressive cognitive impairment associated with
      parkinsonism, visual hallucinations, and fluctuations of attention and
      wakefulness. Current clinical diagnostic criteria emphasize these features and
      also weigh evidence for dopamine cell loss measured with single-photon emission
      computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep
      behavior disorder, a risk factor for the synucleinopathies. The timing of
      dementia relative to parkinsonism is the major clinical distinction between DLB
      and PDD, with dementia arising in the setting of well-established idiopathic
      Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while
      earlier cognitive impairment relative to parkinsonism denotes DLB. The
      distinction between these syndromes continues to be an active research question.
      Treatment for these illnesses remains symptomatic and relies on both
      pharmacologic and nonpharmacologic strategies. SUMMARY: DLB and PDD are important
      and common dementia syndromes that overlap in their clinical features,
      neuropathology, and management. They are believed to exist on a spectrum of Lewy
      body disease, and some controversy persists in their differentiation. Given the
      need to optimize cognition, extrapyramidal function, and psychiatric health,
      management can be complex and should be systematic.

PMID- 27042904
TI  - Frontotemporal Dementias.
AB  - PURPOSE OF REVIEW: This article reviews the common behavioral and cognitive
      features of frontotemporal dementia (FTD) and related disorders as well as the
      distinguishing clinical, genetic, and pathologic features of the most common
      subtypes. RECENT FINDINGS: Advances in clinical phenotyping, genetics, and
      biomarkers have enabled improved predictions of the specific underlying molecular
      pathology associated with different presentations of FTD. Evaluation of large
      international cohorts has led to recent refinements in diagnostic criteria for
      several of the FTD subtypes. SUMMARY: The FTDs are a group of neurodegenerative
      disorders featuring progressive deterioration of behavior or language and
      associated pathology in the frontal or temporal lobes. Based on anatomic,
      genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or
      related disorders are: (1) behavioral variant of FTD, (2) semantic variant
      primary progressive aphasia, (3) nonfluent agrammatic variant primary progressive
      aphasia, (4) corticobasal syndrome, (5) progressive supranuclear palsy, and (6)
      FTD associated with motor neuron disease. Recognition and accurate diagnoses of
      FTD subtypes will aid the neurologist in the management of patients with FTD.

PMID- 27042905
TI  - Vascular Cognitive Impairment.
AB  - PURPOSE OF REVIEW: This article provides a diagnostic framework for vascular
      cognitive impairment, discusses prevalence and relationships to other
      neurodegenerative pathologies, and provides advice on diagnostic workup and
      management. RECENT FINDINGS: Vascular cognitive impairment is the second most
      common cause of cognitive impairment and frequently coexists with other
      neurodegenerative neuropathologies. Three new diagnostic criteria have been
      published recently; common diagnostic elements include the need to classify
      cognitive impairment as mild cognitive impairment or dementia and to link the
      cognitive impairment to evidence of clinically significant cerebrovascular
      disease. Vascular cognitive impairment may be further subclassified into
      poststroke vascular cognitive impairment and nonstroke vascular cognitive
      impairment, most commonly caused by cerebral small vessel disease, which may only
      be recognized on neuroimaging. SUMMARY: Vascular cognitive impairment is a
      potentially treatable common cause of cognitive impairment, progression of which
      may be slowed or halted by secondary prevention of vascular disease.

PMID- 27042906
TI  - Rapidly Progressive Dementia.
AB  - PURPOSE OF REVIEW: This article presents a practical and informative approach to
      the evaluation of a patient with a rapidly progressive dementia (RPD). RECENT
      FINDINGS: Prion diseases are the prototypical causes of RPD, but reversible
      causes of RPD might mimic prion disease and should always be considered in a
      differential diagnosis. Aside from prion diseases, the most common causes of RPD
      are atypical presentations of other neurodegenerative disorders, curable
      disorders including autoimmune encephalopathies, as well as some infections, and
      neoplasms. Numerous recent case reports suggest dural arterial venous fistulas
      sometimes cause RPDs. SUMMARY: RPDs, in which patients typically develop dementia
      over weeks to months, require an alternative differential than the slowly
      progressive dementias that occur over a few years. Because of their rapid
      decline, patients with RPDs necessitate urgent evaluation and often require an
      extensive workup, typically with multiple tests being sent or performed
      concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often
      the first diagnosis many neurologists consider when treating a patient with rapid
      cognitive decline. Many conditions other than prion disease, however, including
      numerous reversible or curable conditions, can present as an RPD. This chapter
      discusses some of the major etiologies for RPDs and offers an algorithm for
      diagnosis.

PMID- 27042907
TI  - Autoimmune Encephalopathies and Dementias.
AB  - PURPOSE OF REVIEW: This article describes the methods of diagnosis and management
      of autoimmune encephalopathies and dementias. The expedited distinction of
      autoimmune encephalopathies and dementias from neurodegenerative disorders is
      important because treatment is most effective at the early stage of illness.
      RECENT FINDINGS: The spectrum of antibody biomarkers of treatable autoimmune
      encephalopathies continues to broaden and now includes antibodies targeting
      glutamate receptors (N-methyl-D-aspartate [NMDA] and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid [AMPA]), gamma-aminobutyric acid A and B (GABA-A
      and GABA-B) receptors, glycine receptors, potassium channel complexes (Kv1, which
      includes leucine-rich, glioma inactivated 1 [LgI1], contactin-associated
      proteinlike 2 [CASPR2], and unknown specificity, and Kv4.2, which includes
      dipeptidyl-peptidase 6 [DPPX]), and glutamic acid decarboxylase 65 (GAD65). Early
      treatment of certain autoimmune encephalopathies with rituximab or
      cyclophosphamide improves outcome when corticosteroids, IV immunoglobulin (IVIg),
      and plasma exchange have proven ineffective. SUMMARY: Despite the progress made
      in diagnostics, in many instances, patients with immunotherapy-responsive
      encephalopathies and dementias are seronegative for encephalitis-specific
      antibodies. Other clues to an autoimmune cause include a subacute symptom onset,
      rapid progression, personal history of autoimmunity or cancer, an inflammatory
      CSF, non-neural antibodies detected in serum, and a response to immunotherapy.

PMID- 27042908
TI  - Adult-Onset Leukoencephalopathies.
AB  - PURPOSE OF REVIEW: This article describes the clinical, genetic, and radiographic
      features of inherited leukoencephalopathies presenting in adulthood. RECENT
      FINDINGS: In recent years, the molecular basis for several inherited
      leukoencephalopathies, presenting exclusively in adults, has been discovered.
      Inherited leukoencephalopathies, previously described in children, have been
      found to have milder or later onset forms presenting in adults. SUMMARY: Although
      individually rare, inherited leukoencephalopathies are important to consider in
      the differential diagnosis of cognitive decline. Patients with inherited
      leukoencephalopathies frequently present to multiple sclerosis and dementia
      clinics. Clinical and radiographic features can be used to guide investigations
      in these patients.

PMID- 27042909
TI  - Diagnosis and Treatment of Idiopathic Normal Pressure Hydrocephalus.
AB  - PURPOSE OF REVIEW: This article provides neurologists with a pragmatic approach
      to the diagnosis and treatment of idiopathic normal pressure hydrocephalus
      (iNPH), including an overview of: (1) key symptoms and examination and radiologic
      findings; (2) use of appropriate tests to determine the patient's likelihood of
      shunt responsiveness; (3) appropriate referral to tertiary centers with expertise
      in complex iNPH; and (4) the contribution of neurologists to the care of patients
      with iNPH following shunt surgery. RECENT FINDINGS: The prevalence of iNPH is
      higher than previously estimated; however, only a fraction of persons with the
      disorder receive shunt surgery. iNPH should be considered as a diagnosis for
      patients with unexplained symmetric gait disturbance, a frontal-subcortical
      pattern of cognitive impairment, and urinary urge incontinence, whose MRI scans
      show enlarged ventricles and whose comorbidities are not sufficient to explain
      their symptoms. Physiologically based tests, such as the tap test (large-volume
      lumbar puncture) or temporary spinal catheter insertion for external lumbar
      drainage with gait testing before and after CSF removal, or CSF infusion testing
      for measurement of CSF outflow resistance, can reliably identify patients who are
      likely to respond to shunt surgery. Properly selected patients have an 80% to 90%
      chance of responding to shunt surgery, and all symptoms can improve following
      shunt surgery. Longitudinal care involves investigating the differential
      diagnosis of any symptoms that either fail to respond to shunt surgery or that
      worsen after initial improvement from shunt surgery. SUMMARY: Neurologists play
      an important role in the identification of patients who should be evaluated for
      possible iNPH. With contemporary diagnostic tests and treatment with programmable
      shunts, the benefit-to-risk ratio of shunt surgery is highly favorable. For more
      complex patients, tertiary centers with expertise in complex iNPH are available
      throughout the world.

PMID- 27042911
TI  - Ethical Considerations for the Use of Next-Generation Alzheimer Drugs in
      Symptomatic and At-Risk Patients.
AB  - This article presents a case in which a patient with mild Alzheimer disease
      requests a prescription for a newly developed Alzheimer disease drug, after which
      the patient's daughter inquires about its potential usefulness as a prevention
      strategy for herself. The article discusses the physician's responsibility to
      balance the ethical principles of beneficence, nonmaleficence, and respect for
      patient autonomy when evaluating requests for medications from patients with
      neurocognitive disease as well as from asymptomatic but at-risk patients. 

PMID- 27042912
TI  - Caregiver Stress and the Patient With Dementia.
AB  - Informal caregivers (often, but not exclusively, family members) are essential to
      the clinical care of a patient with dementia. Most caregivers are untrained and
      unpaid. As a result, caregivers often experience stress caused by the caregiving
      experience; they are the "invisible second patients" in dementia care. Clinicians
      can help caregivers by supporting them in their role and by referring them to
      additional resources for support. 

PMID- 27042913
TI  - Coding for Dementia.

PMID- 27042910
TI  - Psychiatric Aspects of Dementia.
AB  - PURPOSE OF REVIEW: The psychiatric aspects of dementia are increasingly
      recognized as significant contributors to distress, disability, and care burden,
      and, thus, are of increasing interest to practicing neurologists. This article
      examines how psychiatric disorders are entwined with dementia and describes the
      predictive, diagnostic, and therapeutic implications of the psychiatric symptoms
      of dementia. RECENT FINDINGS: Psychiatric disorders, particularly depression and
      schizophrenia, are associated with higher risk for late-life dementia.
      Psychiatric phenomena also define phenotypes such as frontotemporal dementia and
      dementia with Lewy bodies, cause distress, and amplify dementia-related
      disabilities. Management requires a multidisciplinary team, a problem-solving
      stance, programs of care, and pharmacologic management. Recent innovations
      include model programs that provide structured problem-solving interventions and
      tailored in-home care. SUMMARY: There is new appreciation of the complexity of
      the relationship between psychiatric disorders and dementia as well as the
      significance of this relationship for treatment, community services, and
      research.

PMID- 27042917
TI  - Patient Management Problem.

PMID- 27042920
TI  - The HATs We Wear: Literally and Figuratively.

PMID- 27042923
TI  - Drugs to Treat Alzheimer's Disease.

PMID- 27042924
TI  - Safety and Abuse Liability of Oxazepam: Is This Benzodiazepine Drug
      Underutilized?
AB  - Benzodiazepine drugs are controversial because of safety and abuse liability
      concerns, although they have clinically relevant pharmacological differences. The
      current article reviews studies pertaining to the pharmacology, safety, and abuse
      liability of oxazepam. Compared to other benzodiazepine drugs, oxazepam has a
      favorable safety and abuse liability profile, which may be related to its
      pharmacology. Oxazepam is more slowly absorbed and enters the brain more slowly
      than other benzodiazepine drugs; it does not have active metabolites and does not
      accumulate with chronic dosing; its metabolism is not affected by age or by
      mild/moderate liver disease; and it is not prone to drug-drug interactions.
      Oxazepam also binds to the translocator protein, which stimulates the synthesis
      of neurosteroids, and this effect may contribute to its reduced abuse liability.

PMID- 27042925
TI  - Adolescents Who Self-Injure.
AB  - Children and adolescents engage in non-suicidal self-injury (NSSI) at a much
      higher frequency than parents and caregivers may estimate. This form of self
      injury has long been distinguished from suicide, with distinct risk factors and
      comorbidities for each behavior. Although the outcome of NSSI is less devastating
      than suicide, adolescents who self-injure are suffering. Adolescents live and
      move within a particular context and view the world from a unique developmental
      perspective. Treatment should proceed from alliance with the patient and an
      understanding of the context in which he/she lives. Modifiable risk factors have
      been identified and several treatments are shown to reduce frequency of self
      injury. Some interventions have been shown to actually increase distress. Nurses
      are in a position to identify adolescents who self-injure and connect the whole
      family system to appropriate effective intervention.

PMID- 27042926
TI  - Text Messaging for Psychiatric Outpatients: Effect on Help-Seeking and Self
      Harming Behaviors.
AB  - A mobile phone intervention was developed and tested with 30 psychiatric
      outpatients with mental illness, who had high ideation for suicide. The
      intervention involved promoting help-seeking behaviors by sending text messages,
      including information about social welfare services and reminders about medical
      appointments, for 6 months. After the intervention period, the number of
      participants who used social services significantly increased, and more than 80%
      of participants reported that the text messaging service was helpful and useful.
      Compared to baseline, participants' self-harming behaviors decreased and the
      attending psychiatrists rated their suicide ideation as weaker. This is the first
      intervention study to promote psychiatric patients' help-seeking using text
      messaging, and although it was not a randomized controlled trial, this
      intervention has practical value and may lead to the prevention of suicide.

PMID- 27042927
TI  - Reflective Prompts to Guide Termination of the Psychiatric Clinical Student
      Nursing Experience.
AB  - The average length of stay on psychiatric inpatient units has decreased in the
      past 40 years from 24.9 to 7.2 days. Inpatient psychiatric nurses are challenged
      to meet the standards and scope of practice despite the changing circumstances of
      their work environment. The amount of time student nurses spend with a given
      patient has been affected by changes in acute psychiatric inpatient care and
      decreased length of stay; however, opportunities exist for effective termination
      of the nurse-client relationship. Facilitation of students' awareness and
      understanding of the dynamics inherent in the termination process is an important
      teaching task for psychiatric nursing clinical instructors. In the current
      article, a clinically focused learning activity using structured prompts to guide
      and promote psychiatric nursing students' experiences with the process of
      termination is described and teaching strategies are discussed.

PMID- 27042928
TI  - Sensory Modulation Treatment on a Psychiatric Inpatient Unit: Results of a Pilot
      Program.
AB  - The purpose of the current pilot program was to measure efficacy of sensory
      modulation treatment for adults (N = 20) admitted to an inpatient, involuntary
      psychiatric unit. Efficacy of 1-hour group (n = 10) and 1-hour individual (n = 9)
      sensory modulation treatment was measured via pre- and postintervention self
      rating scales (visual analog scale from 0 to 10, with 0 = low arousal and 10 =
      high arousal) and post-survey. Results indicated treatment elicited an average
      self-perceived change in arousal of 1.93. Group treatment elicited an average
      self-rating change of 1.79, whereas individual treatment elicited an average
      change of 2.67. For participants who initially rated their arousal level >=6,
      group treatment elicited a change of 4.5, whereas individual treatment elicited a
      change of 7.5. Participants sought materials and activities that were primarily
      categorized into the olfactory, gustatory, and auditory sensory systems.

PMID- 27042930
TI  - Preclinical evaluation of an endoscopic electroporation system.
AB  - BACKGROUND AND STUDY AIMS: Targeted delivery of specific chemotherapeutic drugs
      into tumors can be achieved by delivering electrical pulses directly to the tumor
      tissue. This causes a transient formation of pores in the cell membrane that
      enables passive diffusion of normally impermeant drugs. A novel device has been
      developed to enable the endoscopic delivery of this tumor permeabilizing
      treatment. The aim of the preclinical studies described here was to investigate
      the efficacy and safety of this nonthermal ablation system in the treatment of
      gastrointestinal cancer models. METHODS: Murine, porcine, and canine
      gastrointestinal tumors and tissues were used to assess the efficacy and safety
      of electroporation delivered through the special device in combination with
      bleomycin. Tumor cell death, volume, and overall survival were recorded. RESULTS:
      Murine tumors treated with electrochemotherapy showed excellent responses, with
      cell death being induced rapidly, mainly via an apoptotic-type mechanism. Use of
      the system in canine gastrointestinal cancers demonstrated successful local
      endoluminal tumor resolution, with no safety or adverse effects noted.
      CONCLUSIONS: Electroporation via the new device in combination with bleomycin
      offers a nonthermal tumor ablative approach, and presents clinicians with a new
      option for the management of gastrointestinal cancers.

PMID- 27042931
TI  - Rationale and design of the European Polyp Surveillance (EPoS) trials.
AB  - BACKGROUND: Current guidelines recommend surveillance colonoscopies after polyp
      removal depending on the number and characteristics of polyps, but there is a
      lack of evidence supporting the recommendations. This report outlines the
      rationale and design of two randomized trials and one observational study
      investigating evidence-based surveillance strategies following polyp removal.
      Study design and endpoints: The EPoS studies started to recruit patients in April
      2015. EPoS study I randomizes 13 746 patients with low-risk adenomas (1 - 2
      tubular adenomas size < 10 mm, low-grade dysplasia) to surveillance after 5 and
      10 years, or 10 years only. EPoS study II randomizes 13 704 patients with high
      risk adenomas (3 - 10 adenomas or adenoma >= 10 mm in diameter, or adenoma with
      high-grade dysplasia, or > 25 % villous features) to surveillance after 3, 5, and
      10 years, or 5 and 10 years only. EPoS study III offers surveillance after 5 and
      10 years to patients with serrated polyps >= 10 mm in diameter at any location,
      or serrated polyps >= 5 mm in diameter proximal to the splenic flexure. All
      polyps are removed before patients enter the trials. The primary end point is
      colorectal cancer incidence after 10 years. We assume a colorectal cancer risk of
      1 % for patients in EPoS I, and 2 % for patients in EPoS II. Using a
      noninferiority hypothesis with an equivalence interval of 0.5 % for EPoS I and
      0.7 % for EPoS II, the trials are 90 % powered to uncover differences larger than
      the equivalence intervals. For EPoS III, no power analyses have been performed.
      CONCLUSIONS: The present trials aim to develop evidence-based strategies for
      polyp surveillance, thereby maximizing effectiveness and minimizing resources.
      TRIAL REGISTRATION: ClinicalTrials.gov (NCT02319928).

PMID- 27042932
TI  - Ritual human sacrifice promoted and sustained the evolution of stratified
      societies.
AB  - Evidence for human sacrifice is found throughout the archaeological record of
      early civilizations, the ethnographic records of indigenous world cultures, and
      the texts of the most prolific contemporary religions. According to the social
      control hypothesis, human sacrifice legitimizes political authority and social
      class systems, functioning to stabilize such social stratification. Support for
      the social control hypothesis is largely limited to historical anecdotes of human
      sacrifice, where the causal claims have not been subject to rigorous quantitative
      cross-cultural tests. Here we test the social control hypothesis by applying
      Bayesian phylogenetic methods to a geographically and socially diverse sample of
      93 traditional Austronesian cultures. We find strong support for models in which
      human sacrifice stabilizes social stratification once stratification has arisen,
      and promotes a shift to strictly inherited class systems. Whilst evolutionary
      theories of religion have focused on the functionality of prosocial and moral
      beliefs, our results reveal a darker link between religion and the evolution of
      modern hierarchical societies. 

PMID- 27042934
TI  - Direct observation of dynamic shear jamming in dense suspensions.
AB  - Liquid-like at rest, dense suspensions of hard particles can undergo striking
      transformations in behaviour when agitated or sheared. These phenomena include
      solidification during rapid impact, as well as strong shear thickening
      characterized by discontinuous, orders-of-magnitude increases in suspension
      viscosity. Much of this highly non-Newtonian behaviour has recently been
      interpreted within the framework of a jamming transition. However, although
      jamming indeed induces solid-like rigidity, even a strongly shear-thickened state
      still flows and thus cannot be fully jammed. Furthermore, although suspensions
      are incompressible, the onset of rigidity in the standard jamming scenario
      requires an increase in particle density. Finally, whereas shear thickening
      occurs in the steady state, impact-induced solidification is transient. As a
      result, it has remained unclear how these dense suspension phenomena are related
      and how they are connected to jamming. Here we resolve this by systematically
      exploring both the steady-state and transient regimes with the same experimental
      system. We demonstrate that a fully jammed, solid-like state can be reached
      without compression and instead purely with shear, as recently proposed for dry
      granular systems. This state is created by transient shear-jamming fronts, which
      we track directly. We also show that shear stress, rather than shear rate, is the
      key control parameter. From these findings we map out a state diagram with
      particle density and shear stress as variables. We identify discontinuous shear
      thickening with a marginally jammed regime just below the onset of full, solid
      like jamming. This state diagram provides a unifying framework, compatible with
      prior experimental and simulation results on dense suspensions, that connects
      steady-state and transient behaviour in terms of a dynamic shear-jamming process.

PMID- 27042933
TI  - sFRP2 in the aged microenvironment drives melanoma metastasis and therapy
      resistance.
AB  - Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a
      poorer prognosis than young. This may be due to accumulated cellular damage,
      decreases in adaptive immunity, and chronic inflammation. However, the effects of
      the aged microenvironment on tumour progression have been largely unexplored.
      Since dermal fibroblasts can have profound impacts on melanoma progression, we
      examined whether age-related changes in dermal fibroblasts could drive melanoma
      metastasis and response to targeted therapy. Here we find that aged fibroblasts
      secrete a Wnt antagonist, sFRP2, which activates a multi-step signalling cascade
      in melanoma cells that results in a decrease in beta-catenin and microphthalmia
      associated transcription factor (MITF), and ultimately the loss of a key redox
      effector, APE1. Loss of APE1 attenuates the response of melanoma cells to DNA
      damage induced by reactive oxygen species, rendering the cells more resistant to
      targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both
      angiogenesis and metastasis of melanoma cells. These data provide an integrated
      view of how fibroblasts in the aged microenvironment contribute to tumour
      progression, offering new possibilities for the design of therapy for the
      elderly. 

PMID- 27042936
TI  - The Parkfield tremors reveal slow and fast ruptures on the same asperity.
AB  - The deep extension of the San Andreas Fault is believed to be creeping, but the
      recent observations of tectonic tremors from these depths indicate a complex
      deformation style. In particular, an isolated tremor source near Parkfield has
      been producing a sequence of low-frequency earthquakes that indicates an uncommon
      mechanism of stress accumulation and release. The tremor pattern regularly
      oscillated between three and six days from mid-2003 until it was disrupted by the
      2004 magnitude 6.0 Parkfield earthquake. After that event, the tremor source
      ruptured only about every three days, but over the next two years it gradually
      returned to its initial alternating recurrence pattern. The mechanism that drives
      this recurrence pattern is unknown. Here we use physics-based models to show that
      the same tremor asperity--the region from which the low-frequency earthquakes
      radiate--can regularly slip in slow and fast ruptures, naturally resulting in
      recurrence intervals alternating between three and six days. This unusual slip
      behaviour occurs when the tremor asperity size is close to the critical
      nucleation size of earthquakes. We also show that changes in pore pressure
      following the Parkfield earthquake can explain the sudden change and gradual
      recovery of the recurrence intervals. Our findings suggest a framework for fault
      deformation in which the same asperity can release tectonic stress through both
      slow and fast ruptures.

PMID- 27042935
TI  - Crystal structure of the human sigma1 receptor.
AB  - The human sigma1 receptor is an enigmatic endoplasmic-reticulum-resident
      transmembrane protein implicated in a variety of disorders including depression,
      drug addiction, and neuropathic pain. Recently, an additional connection to
      amyotrophic lateral sclerosis has emerged from studies of human genetics and
      mouse models. Unlike many transmembrane receptors that belong to large,
      extensively studied families such as G-protein-coupled receptors or ligand-gated
      ion channels, the sigma1 receptor is an evolutionary isolate with no discernible
      similarity to any other human protein. Despite its increasingly clear importance
      in human physiology and disease, the molecular architecture of the sigma1
      receptor and its regulation by drug-like compounds remain poorly defined. Here we
      report crystal structures of the human sigma1 receptor in complex with two
      chemically divergent ligands, PD144418 and 4-IBP. The structures reveal a
      trimeric architecture with a single transmembrane domain in each protomer. The
      carboxy-terminal domain of the receptor shows an extensive flat, hydrophobic
      membrane-proximal surface, suggesting an intimate association with the cytosolic
      surface of the endoplasmic reticulum membrane in cells. This domain includes a
      cupin-like beta-barrel with the ligand-binding site buried at its centre. This
      large, hydrophobic ligand-binding cavity shows remarkable plasticity in ligand
      recognition, binding the two ligands in similar positions despite dissimilar
      chemical structures. Taken together, these results reveal the overall
      architecture, oligomerization state, and molecular basis for ligand recognition
      by this important but poorly understood protein. 

PMID- 27042937
TI  - Clinician Factors Associated With Prostate-Specific Antigen Screening in Older
      Veterans With Limited Life Expectancy.
AB  - IMPORTANCE: Despite guidelines recommending against prostate-specific antigen
      (PSA) screening in elderly men with limited life expectancy, PSA screening
      remains common. OBJECTIVE: To identify clinician characteristics associated with
      PSA screening rates in older veterans stratified by life expectancy. DESIGN,
      SETTING, AND PARTICIPANTS: Cross-sectional study of 826 286 veterans 65 years or
      older eligible for PSA screening who had VA laboratory tests performed in 2011 in
      the VA health care system. MAIN OUTCOMES AND MEASURES: The primary outcome was
      the percentage of men with a screening PSA test in 2011. Limited life expectancy
      was defined as age of at least 85 years with Charlson comorbidity score of 1 or
      greater or age of at least 65 years with Charlson comorbidity score of 4 or
      greater. Primary predictors were clinician characteristics including degree
      training level, specialty, age, and sex. We performed log-linear Poisson
      regression models for the association between each clinician characteristic and
      PSA screening stratified by patient life expectancy and adjusted for patient
      demographics and clinician clustering. RESULTS: In 2011, 466 017 (56%) of older
      veterans received PSA screening, including 39% of the 203 717 men with limited
      life expectancy. After adjusting for patient demographics, higher PSA screening
      rates in patients with limited life expectancy was associated with having a
      clinician who was an older man and was no longer in training. The PSA screening
      rates ranged from 27% for men with a physician trainee to 42% for men with an
      attending physician (P < .001); 22% for men with a geriatrician to 82% for men
      with a urologist as their clinician (P < .001); 29% for men with a clinician 35
      years or younger to 41% for those with a clinician 56 years or older (P < .001);
      and 38% for men with a female clinician older than 55 years vs 43% for men with a
      male clinician older than 55 years (P < .001). CONCLUSIONS AND RELEVANCE: More
      than one-third of men with limited life expectancy received PSA screening. Men
      whose clinician was a physician trainee had substantially lower PSA screening
      rates than those with an attending physician, nurse practitioner, or physician
      assistant. Interventions to reduce PSA screening rates in older men with limited
      life expectancy should be designed and targeted to high-screening clinicians-
      older male, nontrainee clinicians-for greatest impact.

PMID- 27042938
TI  - Precision Medicine for Charcot-Marie-Tooth Disease.

PMID- 27042939
TI  - Nurses and Industry: Conflict or Collaboration?

PMID- 27042940
TI  - Insight into Biological Effects of Zinc Oxide Nanoflowers on Bacteria: Why
      Morphology Matters.
AB  - Zinc oxides have gained exciting achievements in antimicrobial fields because of
      their advantageous properties, whereas their biological effects on bacteria are
      currently underexplored. In this study, biological effects of flower-shaped nano
      zinc oxides on bacteria were systematically investigated. Zinc oxide nanoflowers
      with controllable morphologies (viz., rod flowers, fusiform flowers, and petal
      flowers) were synthesized by modulating merely base type and concentration using
      the hydrothermal process. Their antibacterial power is in an order of petal
      flowers > fusiform flowers > rod flowers because of their differences in
      microscopic parameters such as specific surface area, pore size, and Zn-polar
      plane, etc. More importantly, the role of morphology in influencing biological
      effect on bacteria was examined, focusing on the morphology-induced effect on
      integrality of cell wall, permeability of cell membrane, DNA cleavage, etc. As
      for cytotoxicity, all petal flowers, fusiform flowers, and rod flowers show
      trivial cytotoxicity to the Hela cells. This work provides a guide for enhancing
      biological effect of the biocides on pathogenic bacteria by the morphological
      modulation.

PMID- 27042941
TI  - Theoretical Predictions of Temperature-Induced Gelation in Aqueous Dispersions
      Containing PEO-Grafted Particles.
AB  - In this work, we utilize classical polymer density functional theory (DFT) to
      study gelation in systems containing colloidal particles onto which polymers are
      grafted. The solution conditions are such that the corresponding bulk system
      displays a lower critical solution temperature (LCST). We specifically compare
      our predictions with experimental results by Shay et al. (J. Rheol. 2001, 45, 913
      927), who investigated temperature response in aqueous dispersions containing
      polystyrene particles (PS), with grafted 45-mer poly(ethylene oxide) (PEO)
      chains. Our DFT treatment is based on a model for aqueous PEO solutions that was
      originally developed by Karlstrom for bulk solutions. In this model, monomers are
      assumed to be in either of two classes of states, labeled A and B, where B is
      more solvophobic than A. On the other hand, the degeneracy of B exceeds that of
      A, causing the population of solvophobic monomers to increase with temperature.
      In agreement with experimental findings by Shay et al., we locate gelation at
      temperatures considerably below TTheta, and far below the LCST for such chain
      lengths. This gelation occurs also without any dispersion interactions between
      the PS particles. Interestingly, the polymer-induced interaction free energy
      displays a nonmonotonic dependence on the grafting density. At high grafting
      densities, bridging attractions between grafted layers take place (considerably
      below TTheta). At low grafting densities, on the other hand, the polymers are
      able to bridge across to the other particle surface. Shay et al. conducted their
      experiments at very low ionic strength, using deionized water as a solvent. We
      demonstrate that even minute amounts of adsorbed charge on the surface of the
      particles, can lead to dramatic changes of the gelation temperature, especially
      at high grafting densities. Another interesting prediction is the existence of
      elongated (chainlike) equilibrium structures, at low particle concentrations. We
      emphasize that our model does not rely upon any temperature-dependent
      interactions.

PMID- 27042942
TI  - Temperature Response of Rhodamine B-Doped Latex Particles. From Solution to
      Single Particles.
AB  - Nanoparticle-based temperature imaging is an emerging field of advanced
      applications. Herein, the sensitivity of the fluorescence of rhodamine B-doped
      latex nanoparticles toward temperature is described. Submicrometer size latex
      particles were prepared by a surfactant-free emulsion polymerization method that
      allowed a simple and inexpensive way to incorporate rhodamine B into the
      nanoparticles. Also, rhodamine B-coated latex nanoparticles dispersed in water
      were prepared in order to address the effect of the dye location in the
      nanoparticles on their temperature dependence. A better linearity of the
      temperature dependence emission of the rhodamine B-embedded latex particles, as
      compared to that of free rhodamine B dyes or rhodamine B-coated latex particles,
      is observed. Temperature-dependent fluorescence measurements by fluorescent
      confocal microscopy on individual rhodamine B-embedded latex particles were found
      similar to those obtained for fluorescent latex nanoparticles in solution,
      indicating that these nanoparticles could be good candidates to probe thermal
      processes as nanothermometers.

PMID- 27042943
TI  - Mannolides A-C with an Intact Diterpenoid Skeleton Providing Insights on the
      Biosynthesis of Antitumor Cephalotaxus Troponoids.
AB  - Three new diterpenoids, mannolides A-C (1-3), and two new Cephalotaxus
      troponoids, 4 and 5, were isolated from Cephalotaxus mannii and structurally
      characterized by spectroscopic data and X-ray crystallography. The discovery of
      compounds 1-3 featuring a new intact carbon skeleton, proposed as cephalotane,
      sheds new light on the biogenesis of Cephalotaxus troponoids, a rare class of
      antitumor C19 norditerpenoids. Antitumor tests showed that the tropone motif is
      essential for the activity. 

PMID- 27042944
TI  - Improved Side Chain Dynamics in MARTINI Simulations of Protein-Lipid Interfaces.
AB  - Specific interactions of protein side chains and lipid membranes regulate the
      localization, orientation, and activity of many peripheral proteins. Here, we
      introduce a modification of the coarse-grained MARTINI protein model, called
      'side chain fix' (scFix), that was necessary and sufficient to correctly sample
      the side chain dynamics of beta-strands in several globular proteins. When
      compared to MUs long atomistic simulations or previous experimental findings,
      scFix MARTINI simulations reproduced all key interactions between the well
      studied PLC-delta1 pleckstrin homology domain and a phosphatidylinositol-4,5
      bisphosphate (PIP2) containing lipid membrane. Moreover, the extended runtime and
      higher sampling speed enabled the systematic mapping of the protein's rolling
      motion at the membrane, the identification of short-lived and stable binding
      orientations, as well as the verification and prediction of already known and of
      novel transient PIP2 binding sites. scFix also showed promise to maintain proper
      side chain orientation in other secondary structural motifs of the alpha-spectrin
      SH3 domain, the B1 domain of protein G, and the villin headpiece. This suggests
      that scFix improves on the predictive power of MARTINI simulations regarding
      protein-lipid and protein-ligand interactions. 

PMID- 27042946
TI  - Measuring the Composition and Stable-Isotope Labeling of Algal Biomass
      Carbohydrates via Gas Chromatography/Mass Spectrometry.
AB  - We have developed a method to measure carbohydrate composition and stable-isotope
      labeling in algal biomass using gas chromatography/mass spectrometry (GC/MS). The
      method consists of two-stage hydrochloric acid hydrolysis, followed by chemical
      derivatization of the released monomer sugars and quantification by GC/MS. Fully
      (13)C-labeled sugars are used as internal standards for composition analysis.
      This convenient, reliable, and accurate single-platform workflow offers
      advantages over existing methods and opens new opportunities to study
      carbohydrate metabolism of algae under autotrophic, mixotrophic, and
      heterotrophic conditions using metabolic flux analysis and isotopic tracers such
      as (2)H2O and (13)C-glucose.

PMID- 27042945
TI  - Emerging role of high-resolution imaging in the detection of renal
      osteodystrophy.
AB  - The term renal osteodystrophy refers to changes in bone morphology induced by
      chronic kidney disease (CKD) and represents the skeletal component of the entity
      'chronic kidney disease - mineral and bone disorder'. Changes in turnover,
      mineralization, mass and microarchitecture impair bone quality, compromising
      strength and increasing susceptibility to fractures. Fractures are more common in
      CKD compared with the general population and result in increased morbidity and
      mortality. Screening for fracture risk and management of renal osteodystrophy are
      hindered by the complex, and still only partially understood, pathophysiology and
      the inadequacy of currently available diagnostic methods. Bone densitometry and
      bone turnover markers, although potentially helpful, have significant limitations
      in patients with CKD, and the 'gold standard' test of bone biopsy is infrequently
      performed in routine clinical practice. However, recent advances in high
      resolution bone microarchitecture imaging may offer greater potential for
      quantification and assessment of bone structure and strength and, when used in
      conjunction with serum biomarkers, may allow non-invasive testing for a
      diagnostic virtual bone biopsy. 

PMID- 27042947
TI  - Access to Isoquinolines and Isoquinolin-3-ols via Rh(III)-Catalyzed
      Coupling/Cyclization Cascade Reaction of Arylimidates and Diazo Compounds.
AB  - A Rh(III)-catalyzed coupling/cyclization cascade reaction is described, which
      involves arylimidates and diazo compounds and proceeds via intermolecular C-C
      bond formation and subsequent intramolecular C-N bond formation. Mechanistic
      investigation revealed that the reaction is a two-step process: the initial
      Rh(III)-catalyzed coupling/cyclization proceeds very fast and the following
      dehydration is rather slow. The reaction provides a direct approach to
      isoquinolines and isoquinolin-3-ols without any oxidants.

PMID- 27042948
TI  - Fibroblast growth factor 21 signaling: The liver in focus.

PMID- 27042949
TI  - Head and neck chondrosarcomas: Analysis of the Surveillance, Epidemiology, and
      End Results database.
AB  - BACKGROUND: Chondrosarcoma is a rare tumor of the head and neck. Because of the
      limited clinical data, no studies have conducted a thorough comparison between
      head and neck chondrosarcomas and those arising at other body sites. METHODS:
      Using the Surveillance, Epidemiology, and End Results (SEER) database, we
      compared 682 patients with chondrosarcomas of the head and neck with 4757
      patients with non-head and neck chondrosarcomas, evaluating disease-specific
      survival (DSS) and overall survival (OS) based on tumor location, histology,
      grade, stage, and treatment. RESULTS: Head and neck chondrosarcomas displayed a
      lower grade (p < .001) and stage (p < .0001) compared with other chondrosarcomas.
      Overall, chondrosarcomas of the head and neck had significantly higher DSS and OS
      than non-head and neck chondrosarcomas (p < .001). CONCLUSION: Chondrosarcomas of
      the head and neck display a lower grade and stage compared with other
      chondrosarcomas. DSS and OS were significantly greater for chondrosarcomas of the
      head and neck. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1359-1366, 2016.

PMID- 27042951
TI  - Crosstalk between cardiomyocyte-rich perivascular tissue and coronary arteries is
      reduced in the Zucker Diabetic Fatty rat model of type 2 diabetes mellitus.
AB  - AIM: We tested the hypothesis that crosstalk between cardiomyocyte-rich
      perivascular tissue (PVT) and coronary arteries is altered in diabetes. METHODS:
      We studied the vasoactive effects of PVT in arteries from the Zucker Diabetic
      Fatty (ZDF) rat model of type 2 diabetes, streptozotocin (STZ)-treated Wistar
      rats with type 1 diabetes, and corresponding - heterozygous Zucker Lean (ZL) or
      vehicle-treated Wistar - control rats. Vasocontractile and vasorelaxant functions
      of coronary septal arteries with and without PVT were investigated using wire
      myography. RESULTS: After careful removal of PVT, vasoconstriction in response to
      serotonin and thromboxane analogue U46619 was similar in arteries from ZDF and ZL
      rats, whereas depolarization-induced vasoconstriction - caused by elevating
      extracellular [K+ ] - was reduced in arteries from ZDF compared to ZL rats. PVT
      inhibited serotonin-, U46619- and depolarization-induced vasoconstriction in
      arteries from ZL rats, but this anticontractile influence of PVT was attenuated
      in arteries from ZDF rats. Methacholine-induced vasorelaxation was smaller in
      arteries from ZDF than ZL rats both with and without PVT, and the antirelaxant
      influence of PVT was comparable between arteries from ZDF and ZL rats. We
      observed no differences in vasoconstriction, vasorelaxation or PVT-dependent
      vasoactive effects between arteries from STZ- and vehicle-treated Wistar rats.
      CONCLUSION: Anticontractile influences of PVT are attenuated in coronary arteries
      from ZDF rats but unaffected in arteries from STZ-treated rats. Signs of
      endothelial dysfunction are evident in coronary septal arteries - with and
      without PVT - from ZDF rats but not STZ-treated rats. We propose that altered
      signalling between cardiomyocyte-rich PVT and coronary arteries can contribute to
      cardiovascular complications in type 2 diabetes mellitus.

PMID- 27042950
TI  - Interhospital transfer handoff practices among US tertiary care centers: A
      descriptive survey.
AB  - BACKGROUND: Interhospital transfer is an understudied area within transitions of
      care. The process by which hospitals accept and transfer patients is not well
      described. National trends and best practices are unclear. OBJECTIVE: To describe
      the demographics of large transfer centers, to identify common handoff practices,
      and to describe challenges and notable innovations involving the interhospital
      transfer handoff process. DESIGN AND PARTICIPANTS: A convenience sample of 32
      tertiary care centers in the United States was studied. Respondents were
      typically transfer center directors surveyed by phone. MAIN MEASURES: Data
      regarding transfer center demographics, handoff communication practices,
      electronic infrastructure, and data sharing were obtained. RESULTS: The median
      number of patients transferred each month per receiving institution was 700
      (range, 250-2500); on average, 28% of these patients were transferred to an
      intensive care unit. Transfer protocols and practices varied by institution.
      Transfer center coordinators typically had a medical background (78%), and
      critical care-trained registered nurse was the most prevalent (38%). Common
      practices included: mandatory recorded 3-way physician-to-physician conversation
      (84%) and mandatory clinical status updates prior to patient arrival (81%).
      However, the timeline of clinical status updates was variable. Less frequent
      transfer practices included: electronic medical record (EMR) cross-talk
      availability and utilization (23%), real-time transfer center documentation
      accessibility in the EMR (32%), and referring center clinical documentation
      available prior to transport (29%). A number of innovative strategies to address
      challenges involving interhospital handoffs are reported. CONCLUSIONS:
      Interhospital transfer practices vary widely amongst tertiary care centers.
      Practices that lead to improved patient handoffs and reduced medical errors need
      additional prospective evaluation. Journal of Hospital Medicine 2016;11:413-417.
      (c) 2016 Society of Hospital Medicine.

PMID- 27042952
TI  - Computed Tomography-Based Novel Prediction Model for the Outcome of Shockwave
      Lithotripsy in Proximal Ureteral Stones.
AB  - INTRODUCTION AND OBJECTIVES: Computed tomography (CT) is one of the most commonly
      used diagnostic modalities for urinary stone disease. In this study we developed
      a CT and clinical parameter-based prediction model for shockwave lithotripsy
      (SWL) outcome in proximal ureteral stones. MATERIALS AND METHODS: Data from 223
      patients with single proximal ureteral stones treated with SWL between January
      2009 and January 2015 were reviewed retrospectively. Clinical parameters
      including age, sex, body weight, and body mass index (BMI) were analyzed in
      combination with stone-related CT parameters (stone diameter, height, volume,
      location, Hounsfield units [HU], stone-to-skin distance [SSD]), and secondary
      signs (hydronephrosis, perinephric edema, and rim sign). Based on the cutoff
      values determined by c-statistics, a scoring system for the prediction of SWL
      outcome was developed. RESULTS: The success rate was 65.9% (147/223), and in a
      univariate analysis body weight, BMI, SSD (vertical, horizontal), HU, stone
      diameter, height, volume, and all secondary signs were significantly associated
      with the success of SWL. However, on multivariate analysis only BMI (odds ratio
      [OR] = 1.322, confidence interval [CI] 1.156, 1.512, p = 0.00), stone diameter
      (OR = 1.397, CI 1.259, 1.551, p = 0.00), and perinephric edema (grade 0-1 vs 3-4,
      OR = 2.831, CI 1.032, 7.764, p = 0.043) were independent predictors of SWL
      success. The prediction model based on the logistic regression analysis was as
      follows: SWL success = 1/[1 + exp (-10.165 + 0.279 * [BMI] + 0.334 * [diameter] +
      1.040 [perinephric edema])], having an area under the curve of 0.881. In the
      prediction model based on these parameters, scores of 0, 1, 2, and 3 correlated
      with SWL success rates of 98.5%, 65.7%, 31.4%, and 0%, respectively. CONCLUSIONS:
      BMI, stone diameter, and perinephric edema were independent predictors of SWL
      outcome and a prediction model based on these parameters will facilitate decision
      making for SWL in proximal ureteral stones.

PMID- 27042953
TI  - Molecularly Designed, Nitrogen-Functionalized Graphene Quantum Dots for
      Optoelectronic Devices.
AB  - Nitrogen-functionalized graphene quantum dots (NGQDs) with tailorable optical
      properties are prepared by a versatile technique, which allows the highest
      occupied molecular orbital/lowest unoccupied molecular orbital energy levels and
      energy gaps to be continuously varied. The integration of NGQD layers into the
      structures significantly improves the performance of optoelectronic devices. 

PMID- 27042954
TI  - Dealing with missing covariates in epidemiologic studies: a comparison between
      multiple imputation and a full Bayesian approach.
AB  - Incomplete data are generally a challenge to the analysis of most large studies.
      The current gold standard to account for missing data is multiple imputation, and
      more specifically multiple imputation with chained equations (MICE). Numerous
      studies have been conducted to illustrate the performance of MICE for missing
      covariate data. The results show that the method works well in various
      situations. However, less is known about its performance in more complex models,
      specifically when the outcome is multivariate as in longitudinal studies. In
      current practice, the multivariate nature of the longitudinal outcome is often
      neglected in the imputation procedure, or only the baseline outcome is used to
      impute missing covariates. In this work, we evaluate the performance of MICE
      using different strategies to include a longitudinal outcome into the imputation
      models and compare it with a fully Bayesian approach that jointly imputes missing
      values and estimates the parameters of the longitudinal model. Results from
      simulation and a real data example show that MICE requires the analyst to
      correctly specify which components of the longitudinal process need to be
      included in the imputation models in order to obtain unbiased results. The full
      Bayesian approach, on the other hand, does not require the analyst to explicitly
      specify how the longitudinal outcome enters the imputation models. It performed
      well under different scenarios. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27042955
TI  - Recent advances in the laboratory detection of carbapenemase-producing
      Enterobacteriaceae.
AB  - Carbapenemase-producing Enterobacteriaceae (CPE), mainly Klebsiella pneumoniae
      and Escherichia coli, have been increasing rapidly on a global scale and are
      considered to be significant health threats. The most common carbapenemases are
      KPCs, NDMs, OXA-48-like, IMPs and VIMs but their distribution and prevalence
      differs between countries. The accurate, simple, cost effective and rapid
      detection of carbapenemases in clinical laboratories is an important initial step
      to control the spread of CPE within institutions. The diversity of carbapenemases
      in general, has challenged a simple approach for the detection of most types of
      CPE. This article summarizes the current and describes newer techniques available
      for the detection of carbapenemases among Enterobacteriaceae. The authors also
      provide a simplified approach for the accurate and rapid detection of CPEs that
      can easily be implemented in a clinical diagnostic laboratory.

PMID- 27042956
TI  - SAR prediction in adults and children by combining measured B1+ maps and
      simulations at 7.0 Tesla.
AB  - PURPOSE: To predict local and global specific absorption rate (SAR) in individual
      subjects. MATERIALS AND METHODS: SAR was simulated for a head volume coil for two
      imaging sequences: axial T1-weighted "zero" time-of-echo (ZTE) sequence, sagittal
      T2-weighted fluid attenuated inversion recovery (FLAIR). Two head models (one
      adult, one child) were simulated inside the coil. For 19 adults and 27 children,
      measured B1 (+) maps were acquired, and global (head) SAR estimated by the system
      was recorded. We performed t-test between the B1 (+) in models and human
      subjects. The B1 (+) maps of individual subjects were used to scale the SAR
      simulated on the models, to predict local and global (head) SAR. A phantom
      experiment was performed to validate SAR prediction, using a fiberoptic
      temperature probe to measure the temperature rise due to ZTE scanning. RESULTS:
      The normalized B1 (+) standard deviation in subjects was not significantly
      different from that of the models (P > 0.68 and P > 0.54). The rise in
      temperature generated in the phantom by ZTE was 0.3 degrees C; from the heat
      equation it followed that the temperature-based measured SAR was 2.74 W/kg, while
      the predicted value was 3.1 W/kg. CONCLUSION: For ZTE and FLAIR, limits on
      maximum local and global SAR were met in all subjects, both adults and children.
      To enhance safety in adults and children with 7.0 Tesla MR systems, we suggest
      the possibility of using SAR prediction. J. MAGN. RESON. IMAGING 2016;44:1048
      1055.

PMID- 27042958
TI  - Reply to "Quantitative MRI of the Thymus: Chemical-Shift Ratio, Signal Intensity
      Index, and Apparent Diffusion Coefficient Value".

PMID- 27042957
TI  - Asian consensus statements on endoscopic management of walled-off necrosis. Part
      2: Endoscopic management.
AB  - Walled-off necrosis (WON) is a new term for encapsulated necrotic tissue after
      severe acute pancreatitis. Various terminologies such as pseudocyst, necroma,
      pancreatic abscess, and infected necrosis were previously used in the literature,
      resulting in confusion. The current and past terminologies must be reconciled to
      meaningfully interpret past data. Recently, endoscopic necrosectomy was
      introduced as a treatment option and is now preferred over surgical necrosectomy
      when the expertise is available. However, high-quality evidence is still lacking,
      and there is no standard management strategy for WON. The consensus meeting aimed
      to clarify the diagnostic criteria for WON and the role of endoscopic
      interventions in its management. In the Consensus Conference, 27 experts from
      eight Asian countries took an active role and examined key clinical aspects of
      WON diagnosis and endoscopic management. Statements were crafted based on
      literature review and expert opinion, employing the modified Delphi method. All
      statements were substantiated by the level of evidence and the strength of the
      recommendation. We created 27 consensus statements for WON diagnosis and
      management, including details of endoscopic procedures. When there was not enough
      solid evidence to support the statements, this was clearly acknowledged to
      facilitate future research. Proposed management strategies were formulated and
      are illustrated using flow charts. These recommendations, which are based on the
      best current scientific evidence and expert opinion, will be useful for guiding
      endoscopic management of WON. Part 2 of this statement focused on the endoscopic
      management of WON. 

PMID- 27042959
TI  - Disasters, Queer Narratives, and the News: How Are LGBTI Disaster Experiences
      Reported by the Mainstream and LGBTI Media?
AB  - The media plays a significant role in constructing the public meanings of
      disasters and influencing disaster management policy. In this article, we
      investigate how the mainstream and LGBTI media reported-or failed to report-the
      experiences of lesbian, gay, bisexual, transgender, and intersex (LGBTI)
      populations during disasters in Brisbane, Australia and Christchurch, New
      Zealand. The implications of our work lie within recent disasters research
      suggesting that marginalized populations-including LGBTI peoples-may experience a
      range of specific vulnerabilities during disasters on the basis of their social
      marginality. In this article, we argue that LGBTI experiences were largely absent
      from mainstream media reporting of the Brisbane floods and Christchurch
      earthquake of 2011. Media produced by and about the LGBTI community did take
      steps to redress this imbalance, although with uneven results in terms of
      inclusivity across that community. We conclude by raising the possibility that
      the exclusion or absence of queer disaster narratives may contribute to
      marginality through the media's construction of disasters as experienced
      exclusively by heterosexual family groups.

PMID- 27042961
TI  - Statement of Retraction.

PMID- 27042960
TI  - Retraction: DNAJC6 variants in Parkinson's disease and amyotrophic lateral
      sclerosis.
AB  - The above Letter to the Editor from Annals of Neurology, published online as an
      Accepted Article on 4th April 2016 on Wiley Online Library
      (wileyonlinelibrary.com), has been withdrawn at the request of the authors with
      agreement from the journal editor, Clifford B. Saper, and Wiley Periodicals, Inc.
      The withdrawal has been agreed due to an acknowledgement from the authors that
      they inappropriately implied that material from the PD Gene and ALS Gene public
      databases and a figure from the Max Planck Society for the Advancement of Science
      was their own work. Reference Jiang, T., Zhang, Y-D., Tan, L., and Yu, J-T (2016)
      DNAJC6 variants in Parkinson's disease and amyotrophic lateral sclerosis. Ann
      Neurol. doi: 10.1002/ana.24658.

PMID- 27042962
TI  - Age at Primary Malignancy Determines Survival in Adolescent and Young Adults That
      Develop a Secondary Thyroid Cancer.
AB  - PURPOSE: Second malignancy status is a risk factor for death in adolescent and
      young adults (AYAs) (ages 15-39) with thyroid cancer (TC). This study
      investigates whether age at primary malignancy (PM) is an independent predictor
      of overall survival (OS) for AYA patients diagnosed with secondary TC who have
      survived >=5 years from their PM. METHODS: Surveillance, Epidemiology and End
      Results program (SEER) multiple-primary session (SEER-9 [1973-2010] and SEER-13
      [1992-2010]) identified all secondary TCs in patients <40 years of age who were
      also 5-year survivors. Patients with a thyroid second malignant neoplasm (SMN)
      diagnosed as an AYA were categorized by age at PM (pediatric <15 years vs. AYA).
      Kaplan-Meier and Cox proportional analysis determined OS. RESULTS: Four hundred
      twenty-eight cases of secondary AYA TCs in 5-year cancer survivors were
      identified; 71 had a pediatric PM and 357 an AYA PM. Median OS after a pediatric
      PM was 35.76 years and 33.22 years after an AYA-PM (p = 0.023); only one death
      was due to TC. Race, site and stage of PM, marital status, and three or more
      independent PMs also influenced OS (all p < 0.05). However, TC characteristics,
      stage, and treatment did not affect OS. Cox regression demonstrated that patients
      with an AYA PM had a 5.84 relative risk of death (95% confidence interval [95%
      CI]: 1.81-18.91) compared to patients with a pediatric PM. Among AYAs who develop
      a TC as a second PM, OS is not affected by the TC. The OS for these patients is
      associated with their demographics and the characteristics of their PM: patients
      who are black, male, have three or more primary cancers, and a higher stage of
      their first malignancy are more likely to die. CONCLUSION: For AYA patients with
      thyroid SMNs, having a prior AYA PM (compared to a pediatric PM), Black race, and
      having three or more independent tumors predicted a decreased OS, independent of
      PM type or PM/SMN stage.

PMID- 27042963
TI  - FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line.
AB  - Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies
      implicate tumor immunity in the development of various tumors, including
      malignant mesothelioma. In order to establish an in vitro T-cell model to clarify
      the effects of long-term exposure of asbestos on tumor immunity, in this study,
      human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months
      and the resultant cells (MT-2Rst) were assessed for the expression of forkhead
      transcription factor FoxO1. Gene expression analysis revealed that the amount of
      FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In
      accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma,
      Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells.
      Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic
      parental MT-2 cells after treatment with asbestos. On the other hand, over
      expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells.
      These results suggested that FoxO1 played an important role in regulating
      asbestos-induced apoptosis and confirmed the presence of multiple pathways
      regulating resistance to asbestos in MT-2Rst cells.

PMID- 27042964
TI  - Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.
AB  - BACKGROUND: Current guidelines recommend pulmonary-vein isolation by means of
      catheter ablation as treatment for drug-refractory paroxysmal atrial
      fibrillation. Radiofrequency ablation is the most common method, and cryoballoon
      ablation is the second most frequently used technology. METHODS: We conducted a
      multicenter, randomized trial to determine whether cryoballoon ablation was
      noninferior to radiofrequency ablation in symptomatic patients with drug
      refractory paroxysmal atrial fibrillation. The primary efficacy end point in a
      time-to-event analysis was the first documented clinical failure (recurrence of
      atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of
      antiarrhythmic drugs, or repeat ablation) following a 90-day period after the
      index ablation. The noninferiority margin was prespecified as a hazard ratio of
      1.43. The primary safety end point was a composite of death, cerebrovascular
      events, or serious treatment-related adverse events. RESULTS: A total of 762
      patients underwent randomization (378 assigned to cryoballoon ablation and 384
      assigned to radiofrequency ablation). The mean duration of follow-up was 1.5
      years. The primary efficacy end point occurred in 138 patients in the cryoballoon
      group and in 143 in the radiofrequency group (1-year Kaplan-Meier event rate
      estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence
      interval [CI], 0.76 to 1.22; P<0.001 for noninferiority). The primary safety end
      point occurred in 40 patients in the cryoballoon group and in 51 patients in the
      radiofrequency group (1-year Kaplan-Meier event rate estimates, 10.2% and 12.8%,
      respectively; hazard ratio, 0.78; 95% CI, 0.52 to 1.18; P=0.24). CONCLUSIONS: In
      this randomized trial, cryoballoon ablation was noninferior to radiofrequency
      ablation with respect to efficacy for the treatment of patients with drug
      refractory paroxysmal atrial fibrillation, and there was no significant
      difference between the two methods with regard to overall safety. (Funded by
      Medtronic; FIRE AND ICE ClinicalTrials.gov number, NCT01490814.).

PMID- 27042965
TI  - Pharmacokinetics and tissue distribution of two novel isomerism anticancer
      platinum compounds.
AB  - LLC-0601(S,S) and LLC-0601(R,R) are two novel synthesized isomerism platinum
      compounds both with encouraging anticancer activity. However, the previous study
      showed that toxicity of LLC-0601(R,R) was much higher than that of LLC-0601(S,S)
      with higher body weight loss and mortality rate of tested rats. This paper is
      focused on the comparison of the two compounds with their pharmacokinetic (PK)
      profiles in rats and tissue distribution in mice after intravenous
      administration. The atomic absorption spectrometry (AAS) method was successfully
      developed and applied for the determination of platinum in plasma and tissues.
      The results showed that main PK parameters such as half-life, AUC and MRT of the
      two compounds had no significant difference after intravenous administration to
      rats (p  > 0.05). The tissue distribution after intravenous administration to
      mice showed that the concentration of LLC-0601(R,R) in heart at 0.083 h was
      higher than that of LLC-0601(S,S) (p  < 0.05) and it was the same case for
      AUC5min-4 h (p  < 0.05). Different distribution of the two compounds in heart was
      possibly the main reason of different toxicity and more in-depth research on the
      metabolites and other mechanism are needed to investigate the toxicity. 

PMID- 27042966
TI  - The Effect of Game-Based Interventions in Rehabilitation of Diabetics: A
      Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Game-based interventions have been proposed as a way to improve
      both patient adherence to physical activity (PA) and disease-related knowledge to
      achieve better self-management of blood glucose levels (HbA1c). The objective of
      this study was to systematically review the literature on the effect of game
      based interventions on HbA1c, diabetes-related knowledge, and physical outcomes
      in rehabilitation of diabetes patients. METHODS: We conducted a systematic
      literature search in MEDLINE, EMBASE, PEDro, Scopus, Cochrane Central Register of
      Controlled Trials, CINAHL, and Psych INFO in October 2014 based on a priori
      defined inclusion criteria: patients with diabetes (type 1 or type 2), game-based
      interventions, and randomized controlled trials. RESULTS: The database search
      identified 1,101 potential articles for screening, four of which were eligible
      for the present systematic review. Game-based interventions show no effect on
      HbA1c (three studies) standardized mean difference = -0.10, 95% confidence
      interval = [-0.33, 0.14] compared to usual care or waiting lists. Game-based
      interventions were superior to controls in improving health-related quality of
      life, muscle strength, and balance (one study). No difference was found between
      game-based interventions and usual care or waiting lists in terms of diabetes
      related knowledge (one study). DISCUSSION: PA is important for diabetes
      management. The present review indicates that game-based interventions are not
      superior to ordinary PA in controlling HbA1c. Due to the weak methodological
      quality of the included studies and the very low body of evidence, the likelihood
      that the real effect of game-based interventions will be substantially different
      (i.e., large enough difference to possibly affect decision-making) is high.

PMID- 27042967
TI  - Reactivation tuberculosis: role of surveillance.
AB  - The incidence and death rates from tuberculosis (TB) have declined through
      concerted efforts in the diagnosis and treatment of active disease. Despite this,
      9.6 million new cases and 1.1 million deaths in 2014 are unacceptably high. To
      decrease the rates of TB further, the huge number of persons with latent TB
      infection (LTBI) from whom new cases will arise has to be addressed with a sense
      of priority. Identifying the highest risk groups and providing effective
      treatment has been shown to decrease active TB. Further research to refine the
      predictors of reactivation and shorter effective treatments are urgently needed.
      Implementing intensified case finding, testing and treatment for LTBI will
      require continued investment in health care capacity at multiple levels. 

PMID- 27042968
TI  - Factors associated with adults' perceived need to vaccinate against hepatitis B
      in rural China.
AB  - Hepatitis B virus (HBV) infection is a serious public-health issue in China.
      While the hepatitis B vaccine is effective in preventing HBV infection, the HBV
      vaccination coverage rates among Chinese adults remain low. From a survey of
      rural adults from 7 provinces in China, we identified a unique HBV at-risk group:
      rural adults who had no history of HBV vaccination and had no plan to HBV
      vaccinate in the future. We divided this 'no history-no plan' group into those
      who identified No-need to vaccinate and those that perceived a Need to vaccinate
      (even if they had no plan to do so). We found age, marital status, health status,
      perceived HBV infection environment, perceived HBV infection risk and perceived
      HBV infection severity explained differences between the 'No-need' and 'Need" to
      HBV vaccinate groups. Education, occupation and knowledge of hepatitis B and HBV
      transmission were not associated with HBV vaccination need. Our results showed
      that free HBV vaccinations and reimbursement for vaccinating could significantly
      increase the HBV vaccinate take-up rate for both Need and No-need rural adults. A
      tailored public health HBV campaign, especially targeting the No-need subgroup,
      would increase vaccination rates by better informing rural adults about HBV
      transmission routes, the dangers of HBV infection, the effectiveness of HBV
      vaccinations and the safety of HBV vaccinations.

PMID- 27042969
TI  - Case study: Idiopathic hemothorax in a patient with status asthmaticus.
AB  - INTRODUCTION: Idiopathic spontaneous hemothorax has been rarely described in the
      literature. CASE STUDY: A case of status asthmaticus and spontaneous hemothorax
      is described in a 29-year-old female of African descent who presented to the
      emergency room after 2 days of severe cough productive of yellow sputum, otalgia,
      sore throat, subjective fevers, chills, headache, progressive wheezing, chest
      tightness and dyspnea. She had a history of 7 years of asthma and was non
      adherent with her controller asthma medications. Prophylactic subcutaneous
      administration of enoxaparin 40 milligrams was initiated upon hospitalization.
      The patient initially had a normal chest radiograph but subsequently developed a
      large, left hemothorax that required tube thoracostomy placement followed by
      video-assisted thoracoscopic surgery (VATS). RESULTS: The patient was transferred
      to the Intensive Care Unit (ICU) and tube thoracostomy resulted in evacuation of
      1,400 milliliters of blood-like fluid, which had a pleural fluid hematocrit
      greater than 50% of the serum hematocrit. A contrast-enhanced computed tomography
      (CT) scan of the chest did not reveal any source for the bleeding and a
      technetium bone scan of the chest was normal. The patient required transfusion of
      5 units of packed red blood cells. She was then taken to the operating room for
      VATS because of continued chest tube drainage (3,200 milliliters of fluid over a
      48-hour period). CONCLUSION: The etiology of the hemothorax was unknown despite
      surgical exploration but was felt to be secondary to cough and bronchospasm
      associated with status asthmaticus.

PMID- 27042971
TI  - Every last baby out of every last egg: the appropriate goal for fertility
      treatment in women older than 40 years.

PMID- 27042970
TI  - Increased antimullerian hormone levels and other reproductive endocrine changes
      in adult male relatives of women with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate for differences in reproductive hormone levels in male
      relatives of women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional
      study. SETTING: Academic medical center. PATIENT(S): Sixty-three fathers and 66
      brothers of women with PCOS as well as two groups of control men of comparable
      age to fathers (older control, n = 30) and brothers (younger control, n = 58).
      INTERVENTION(S): A single early morning fasting blood sample was obtained for the
      measurement of reproductive hormone levels. MAIN OUTCOME MEASURE(S):
      Testosterone, LH, FSH, antimullerian hormone (AMH), inhibin B, estradiol (E2),
      and estrone (E1) levels were measured. RESULT(S): The AMH, LH, and FSH levels
      were significantly increased in male relatives compared with their respective
      control groups. The levels of E2, E1, T, and inhibin B did not differ between the
      groups. CONCLUSION(S): The AMH, LH, and FSH levels were increased in adult male
      relatives of women with PCOS, suggesting that they may have altered testicular
      function and changes in neuroendocrine regulation of gonadotropin secretion.
      These changes may reflect effects of PCOS susceptibility genes such as the
      recently mapped chromosome 11p14.1 locus in the region of the FSH B polypeptide
      gene.

PMID- 27042972
TI  - New Genus of Blood Fluke (Digenea: Schistosomatoidea) from Malaysian Freshwater
      Turtles (Geoemydidae) and its Phylogenetic Position Within Schistosomatoidea.
AB  - :  Baracktrema obamai n. gen., n. sp. infects the lung of geoemydid turtles
      (black marsh turtle, Siebenrockiella crassicollis [type host] and southeast Asian
      box turtle, Cuora amboinensis ) in the Malaysian states of Perak, Perlis, and
      Selangor. Baracktrema and Unicaecum Stunkard, 1925 are the only accepted turtle
      blood fluke genera having the combination of a single cecum, single testis,
      oviducal seminal receptacle, and uterine pouch. Baracktrema differs from
      Unicaecum by having a thread-like body approximately 30-50* longer than wide and
      post-cecal terminal genitalia. Unicaecum has a body approximately 8-12* longer
      than wide and terminal genitalia that are anterior to the distal end of the
      cecum. The new genus further differs from all other accepted turtle blood fluke
      genera by having a cecum that is highly convoluted for its entire length, a
      spindle-shaped ovary between the cirrus sac and testis, a uterine pouch that
      loops around the primary vitelline collecting duct, a Laurer's canal, and a
      dorsal common genital pore. Phylogenetic analysis of the D1-D3 domains of the
      nuclear large subunit ribosomal DNA (28S) revealed, with high nodal support and
      as predicted by morphology, that Baracktrema and Unicaecum share a recent common
      ancestor and form a clade sister to the freshwater turtle blood flukes of
      Spirorchis, paraphyletic Spirhapalum, and Vasotrema and that, collectively, these
      flukes were sister to all other tetrapod blood flukes (Hapalorhynchus +
      Griphobilharzia plus the marine turtle blood flukes and schistosomes). Pending a
      forthcoming emended morphological diagnosis of the family, the clade including
      Spirorchis spp., paraphyletic Spirhapalum, Vasotrema, Baracktrema, and Unicaecum
      is a likely placeholder for "Spirorchiidae Stunkard, 1921 " (type genus
      Spirorchis MacCallum, 1918 ; type species Spirorchis innominatus Ward, 1921 ).
      The present study comprises the 17th blood fluke known to infect geoemydid
      turtles and the first proposal of a new genus of turtle blood fluke in 21 yr.

PMID- 27042973
TI  - Fuzzy logic-based assessment for mapping potential infiltration areas in low
      gradient watersheds.
AB  - This paper gives an account of the design a logic-based approach for identifying
      potential infiltration areas in low-gradient watersheds based on remote sensing
      data. This methodological framework is applied in a sector of the Pampa Plain,
      Argentina, which has high level of agricultural activities and large demands for
      groundwater supplies. Potential infiltration sites are assessed as a function of
      two primary topics: hydrologic and soil conditions. This model shows the state of
      each evaluated subwatershed respecting to its potential contribution to
      infiltration mainly based on easily measurable and commonly used parameters:
      drainage density, geomorphologic units, soil media, land-cover, slope and aspect
      (slope orientation). Mapped outputs from the logic model displayed 42% very low
      low, 16% moderate, 41% high-very high contribution to potential infiltration in
      the whole watershed. Subwatersheds in the upper and lower section were identified
      as areas with high to very high potential infiltration according to the following
      media features: low drainage density (<1.5 km/km(2)), arable land and pastures as
      the main land-cover categories, sandy clay loam to loam - clay loam soils and
      with the geomorphological units named poorly drained plain, channelized drainage
      plain and, dunes and beaches. 

PMID- 27042974
TI  - Mix design and pollution control potential of pervious concrete with non
      compliant waste fly ash.
AB  - Pervious concrete mix was optimized for the maximum compressive strength and the
      desired permeability at 7 mm/s with varying percentages of water-to-binder (W/B),
      fly ash-to-binder (FA/B), nano-iron oxide-to-binder (NI/B) and water reducer-to
      binder (WR/B). The mass ratio of coarse aggregates in sizes of 4.75-9.5 mm to the
      binder was fixed at 4:1. Waste FA used in the study was not compliant with a
      standard specification for use as a mineral admixture in concrete. One optimum
      pervious concrete (Opt A) targeting high volume FA utilization had a 28-day
      compressive strength of 22.8 MPa and a permeability of 5.6 mm/s with a mix design
      at 36% W/B, 35% FA/B, 6% NI/B and 1.2% WR/B. The other (Opt B) targeting a less
      use of admixtures had a 28-day compressive strength and a permeability of 21.4
      MPa and 7.6 mm/s, respectively, at 32% W/B, 10% FA/B, 0.5% NI/B and 0.8% WR/B.
      During 10 loads at a 2-h contact time each, the Opt A and Opt B achieved the
      average fecal coliform removals of 72.4% and 77.9% and phosphorus removals of
      49.8% and 40.5%, respectively. Therefore, non-compliant waste FA could be
      utilized for a cleaner production of pervious concrete possessing a greater
      structural strength and compatible hydrological property and pollution control
      potential, compared to the ordinary pervious concrete. 

PMID- 27042975
TI  - Single-cell states versus single-cell atlases - two classes of heterogeneity that
      differ in meaning and method.
AB  - Recent advances have created new opportunities to dissect cellular heterogeneity
      at the omics level. The enthusiasm for deep single-cell profiling has obscured a
      discussion of different types of heterogeneity and the most-appropriate
      techniques for studying each type. Here, I distinguish heterogeneity in
      regulation from heterogeneity in lineage. Snapshots of lineage heterogeneity
      provide a cell atlas that catalogs cellular diversity within complex tissues.
      Profiles of regulatory heterogeneity seek to interrogate one lineage deeply to
      capture an ensemble of single-cell states. Single-cell atlases require molecular
      signatures from many cells at a throughput afforded by mass cytometry-based,
      microfluidic-based, and microencapsulation-based methods. Single-cell states are
      more dependent on time, microenvironment, and low-abundance transcripts,
      emphasizing in situ methods that stress depth of profiling and quantitative
      accuracy.

PMID- 27042976
TI  - Teacher autonomy support reduces adolescent anxiety and depression: An 18-month
      longitudinal study.
AB  - Grounded in stage-environment fit theory, this study adopts a longitudinal design
      to examine the contribution of autonomy support from teachers to reducing
      adolescent anxiety and depression. A total of 236 Chinese adolescents (57.38%
      females, Mage = 14.34) completed questionnaires on teacher autonomy support,
      basic psychological needs satisfaction, school engagement, anxiety, and
      depression in the fall and spring semesters of their 7th and 8th grade years. The
      results showed that teacher autonomy support in the fall of 7th grade boosted
      basic psychological needs satisfaction in the spring of 7th grade; this, in turn,
      increased school engagement in the fall of 8th grade, which subsequently
      decreased anxiety and depression in the spring of 8th grade. These findings
      demonstrated the significant effect of teacher autonomy support on reducing
      adolescent anxiety and depression; furthermore, it highlighted the mediating
      roles of basic psychological needs satisfaction and school engagement in this
      relationship.

PMID- 27042977
TI  - Unique insula subregion resting-state functional connectivity with amygdala
      complexes in posttraumatic stress disorder and its dissociative subtype.
AB  - The insula and amygdala are implicated in the pathophysiology of posttraumatic
      stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non
      dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients,
      respectively, during symptom provocation. However, the functional connectivity
      between individual insula subregions and the amygdala has not been investigated
      in persons with PTSD, with or without the dissociative subtype. We examined
      insula subregion (anterior, mid, and posterior) functional connectivity with the
      bilateral amygdala using a region-of-interest seed-based approach via PickAtlas
      and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD
      DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to
      controls, the PTSD-DS group displayed increased insula connectivity (bilateral
      anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in
      both hemispheres, and the PTSD+DS group displayed increased insula connectivity
      (bilateral anterior, left mid, and left posterior) to the left basolateral
      amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion
      connectivity (bilateral anterior, left mid, and right posterior) to the left
      basolateral amygdala was found in PTSD+DS. Depersonalization/derealization
      symptoms and PTSD symptom severity correlated with insula subregion connectivity
      to the basolateral amygdala within PTSD patients. This study is an important
      first step in elucidating patterns of neural connectivity associated with unique
      symptoms of arousal/interoception, emotional processing, and awareness of bodily
      states, in PTSD and its dissociative subtype.

PMID- 27042979
TI  - Imaginary Transitions and Transformation in Psychoanalytic Work.
AB  - This article explores the transformations that occur in analytic work from
      methodological, topographical, and dynamic perspectives, with a particular
      emphasis on the concept of imaginary transition. Through a theoretical
      exploration and the presentation of clinical material from five cases, the
      authors show how the process of working-through emerges in treatment as a result
      of the changes of rhythm, register, images, phenomena of upheaval, and the
      numerous displacements that are brought about in and through transference. Events
      are only markers or clues about a transformation that takes place over the long
      term. 

PMID- 27042978
TI  - An efficient and environment-friendly method of removing graphene oxide in
      wastewater and its degradation mechanisms.
AB  - Graphene and graphene oxide (GO) have already existed in air, water and soil due
      to their popular application in functional materials. However, degradation of
      graphene and GO in wastewater has not been reported. Degradation of GO plays a
      key role in the elimination of graphene and GO in wastewater due to graphene
      being easily oxidized to GO. In this paper, GO was completely degraded to give
      CO2 by Photo-Fenton. The degradation intermediates were determined by UV-vis
      absorption spectra, elemental analysis (EA), fourier transform infrared (FT-IR)
      and liquid chromatography-mass spectrometry (LC-MS). Experimental results showed
      that graphene oxide was completely degraded to give CO2 after 28 days. Based on
      UV, FT-IR, LC-MS spectra and EA data of these degradation intermediates, the
      degradation mechanisms of GO were supposed. This paper suggests an efficient and
      environment-friendly method to degrade GO and graphene.

PMID- 27042980
TI  - On Interpretative Experiences: Unconcious-to-Unconcious Communication Through
      Reverie, Language, and the Setting.
AB  - Interpretation has been looked upon for decades as the analyst's central tool to
      promote transformation, and it was intended as a synonym for making the
      unconscious conscious. Nowadays, work with patients with unrepresented mental
      areas has become more common and the classical conceptualizations require
      broadening. Reflecting and retrieving the original acceptations of Freud's word
      Deutung, we suggest the existence of "unconscious-to-unconscious" communications
      that we shall call "interpretative experiences," which can promote transformation
      through nonverbal communicative modes, thus getting in touch with more primitive
      mental functioning. Drawing on case material, we discuss the transformative
      function of reverie, language, and the setting within the framework of the post
      Kleinian and French psychoanalytic model. 

PMID- 27042981
TI  - Legacies and Memorializations in the Intergenerational Transmission of Psychic
      Life: Psychoanalytic Notes on Some of the Ways in Which Sons Assume Their
      Father's Mantle.
AB  - The intergenerational transmission of psychic life has been difficult to explore
      psychoanalytically given that a treatment of both parent and child is rarely, if
      ever, feasible. Here the issue is explored in terms of father-son relationships.
      Three legendary fathers (Abraham, Laius, Shiva) are discussed as illustrating the
      filicidal legacy they imposed psychically and corporeally on their sons. Three
      contemporary case vignettes are then presented, indicating ways in which sons
      ambivalently memorialize their fathers. This material provides a model as to some
      of the ways in which sons assume the mantle of the father's conscious and
      unconscious dynamics in the course of their personal history. Paternal legacies
      generate "memorializations" that express profound and poignant conflicts
      animating the son's psychic life. In the context of this investigation, the
      significance of the distinction between actual fathers or father figures (who are
      mortal, who possess some sort of gendered qualities, and who may be present or
      absent, emotionally and physically) and the "symbolic father" (who is the locus
      of the phallus that organizes the possibility of representational discourse) is
      discussed. It is suggested that boys and men typically develop in terms of
      confusions around this distinction. The oedipal conundrum and challenge of the
      boy's passage into manhood is then formulated as follows: Masculinity involves
      both the integration of patricidal desire (in response to the paternal legacy)
      and the mourning of actual fathers or father figures. It also involves the
      acceptance of the human condition, which is both that of mortality and of our
      "castratedness" in relation to the "symbolic father" as the locus of the phallus
      (the only one who knows whereof "He" speaks and acts, and who can neither be
      mourned nor surpassed). 

PMID- 27042982
TI  - Child Sexual Abuse, Baby Gender, and Intergenerational Psychic Transmission: An
      Exploratory, Projective Psychoanalytic Approach.
AB  - The aim of this article is to present a French psychoanalytic model of how and to
      what extent the sequellae of sexual abuse by a male during a girl's childhood are
      transmitted to the next generation, as a function of the gender of the abused
      mother's children. The authors conducted a qualitative exploratory study based on
      the longitudinal follow-up of a woman who had two boys and a girl. They focused
      on the impact of two general sequellae: separation anxiety and negativity
      disqualification of the paternal and/or male figures. From the methodological
      standpoint, they used a clinical interview to assess the mother, and a projective
      tool, a storytelling test, to assess the child's personality using content
      analysis. The results confirm both the merits of the theoretical framework and
      the relevance of the projective methodology for grasping sequellae transmitted to
      the child. The sequellae turned out to be markedly different for the two baby
      genders: rejection for the male, overprotection and ghostly encryption for the
      female. Avenues for using this tool and model in future quantitative, comparative
      studies are suggested. 

PMID- 27042983
TI  - Thinking Forbidden Thoughts: The Oedipus Complex as a Complex of Knowing.
AB  - The Oedipus complex, considered by Freud the "nuclear complex of development,"
      played a central role in the evolution of psychoanalytic thought. This paper
      returns to the point of transition from the seduction theory, Freud's initial
      theorem, to the oedipal model, and suggests that the Oedipus complex is first and
      foremost a text and as such contains a multiplicity of narratives. In particular,
      the author articulates the close relation between the Oedipus complex and the
      subject of knowing, postulating that underlying its surface level, the deep-level
      structure of this complex is one of knowing. As a complex of knowing it is of
      dual quality, both promoting and impeding the ability to know. 

PMID- 27042985
TI  - In Memoriam.

PMID- 27042987
TI  - Quantifying the safety effects of horizontal curves on two-way, two-lane rural
      roads.
AB  - The objective of this study is to quantify the safety performance of horizontal
      curves on two-way, two-lane rural roads relative to tangent segments. Past
      research is limited by small samples sizes, outdated statistical evaluation
      methods, and unreported standard errors. This study overcomes these drawbacks by
      using the propensity scores-potential outcomes framework. The impact of adjacent
      curves on horizontal curve safety is also explored using a cross-sectional
      regression model of only horizontal curves. The models estimated in the present
      study used eight years of crash data (2005-2012) obtained from over 10,000 miles
      of state-owned two-lane rural roads in Pennsylvania. These data included
      information on roadway geometry (e.g., horizontal curvature, lane width, and
      shoulder width), traffic volume, roadside hazard rating, and the presence of
      various low-cost safety countermeasures (e.g., centerline and shoulder rumble
      strips, curve and intersection warning pavement markings, and aggressive driving
      pavement dots). Crash prediction is performed by means of mixed effects negative
      binomial regression using the explanatory variables noted previously, as well as
      attributes of adjacent horizontal curves. The results indicate that both the
      presence of a horizontal curve and its degree of curvature must be considered
      when predicting the frequency of total crashes on horizontal curves. Both are
      associated with an increase in crash frequency, which is consistent with previous
      findings in the literature. Mixed effects negative binomial regression models for
      total crash frequency on horizontal curves indicate that the distance to adjacent
      curves is not statistically significant. However, the degree of curvature of
      adjacent curves in close proximity (within 0.75 miles) was found to be
      statistically significant and negatively correlated with crash frequency on the
      subject curve. This is logical, as drivers exiting a sharp curve are likely to be
      driving slower and with more awareness as they approach the next horizontal
      curve. 

PMID- 27042988
TI  - Driving experience moderates the effect of implicit versus explicit threat
      priming on hazard perception test.
AB  - Due to the controversial evidence regarding the efficacy of threat campaigns on
      driving behavior, we addressed the effects of explicit vs. implicit threats. As
      in other areas of advertisements, we hypothesized that an implicit threat would
      be more effective, i.e., generate more anxiety than an explicit threat.
      Furthermore, we hypothesized that such effects would be moderated by driving
      experience: more experienced drivers when threatened will rely on driving skills
      and perform in a less cautious manner vs. less experienced drivers who have not
      yet acquired these skills, and therefore will tend to calm their fear by
      exercising more caution. Driving behavior in this experimental design was
      addressed by the Hazard Perception (HP) task. Results were as expected. Anxiety
      was higher under implicit vs. explicit threat. HP scores however were overall the
      same for both groups. Implicit priming generated less-cautious behavior in high
      experienced drivers while generating more caution for less-experienced drivers.
      Demonstrating in a single experiment all three driving patterns following threat,
      namely, no change in driving behavior (whole sample), more cautious driving
      behavior (less-experience) and less cautious behavior (more-experience),
      potentially comprises an important step in resolving the aforementioned disparity
      concerning effects of threat campaigns on driving behavior. 

PMID- 27042989
TI  - Relating traffic fatalities to GDP in Europe on the long term.
AB  - Modeling road safety development can provide important insight into policies for
      the reduction of traffic fatalities. In order to achieve this goal, both the
      quantifiable impact of specific parameters, as well as the underlying trends that
      cannot always be measured or observed, need to be considered. One of the key
      relationships in road safety links fatalities with risk and exposure, where
      exposure reflects the amount of travel, which in turn translates to how much
      travelers are exposed to risk. In general two economic variables: GDP and
      unemployment rate are selected to analyse the statistical relationships with some
      indicators of road accident fatality risk. The objective of this research is to
      provide an overview of relevant literature on the topic and outline some recent
      developments in macro-panel data analysis that have resulted in ongoing research
      that has the potential to improve our ability to forecast traffic fatality
      trends, especially under turbulent financial situations. For this analysis, time
      series of the number of fatalities and GDP in 30 European countries for a period
      of 38 years (1975-2012) are used. This process relies on estimating long-term
      models (as captured by long term time-series models, which model each country
      separately). Based on these developments, utilizing state-of-the-art modelling
      and analysis techniques such as the Common Correlated Effects Mean Group
      estimator (Pesaran), the long-term elasticity mean value equals 0.63, and is
      significantly different from zero for 10 countries only. When we take away the
      countries, where the number of fatalities is stationary, the average elasticity
      takes a higher value of nearly 1. This shows the strong sensitivity of the
      estimate of the average elasticity over a panel of European countries and
      underlines the necessity to be aware of the underlying nature of the time series,
      to get a suitable regression model. 

PMID- 27042990
TI  - Once-monthly paliperidone palmitate in recently diagnosed and chronic non-acute
      patients with schizophrenia.
AB  - OBJECTIVE: To explore the treatment response, tolerability and safety of once
      monthly paliperidone palmitate (PP1M) in non-acute patients switched from oral
      antipsychotics, stratified by time since diagnosis as recently diagnosed (<=3
      years) or chronic patients (>3 years). RESEARCH DESIGN AND METHODS: Post hoc
      analysis of a prospective, interventional, single-arm, multicentre, open-label, 6
      month study performed in 233 recently diagnosed and 360 chronic patients. MAIN
      OUTCOME MEASURES: The proportion achieving treatment response (defined as >=20%
      improvement in Positive and Negative Syndrome Scale [PANSS] total score from
      baseline to endpoint) and maintained efficacy (defined as non-inferiority in the
      change in PANSS total score at endpoint [Schuirmann's test]). RESULTS: 71.4% of
      recently diagnosed and 59.2% of chronic patients showed a >=20% decrease in PANSS
      total score (p = 0.0028 between groups). Changes in PANSS Marder factors, PANSS
      subscales, and the proportion of patients with a Personal and Social Performance
      scale (PSP) total score of 71-100 were significantly greater in recently
      diagnosed compared with chronic patients. PP1M was well tolerated, presenting no
      unexpected safety findings. CONCLUSION: These data show that recently diagnosed
      patients treated with PP1M had a significantly higher treatment response and
      improved functioning, as assessed by the PSP total score, than chronic patients.

PMID- 27042991
TI  - DNA repair genes in the Megavirales pangenome.
AB  - The order 'Megavirales' represents a group of eukaryotic viruses with a large
      genome encoding a few hundred up to two thousand five hundred genes. Several
      members of Megavirales possess genes involved in major DNA repair pathways. Some
      of these genes were likely inherited from an ancient virus world and some others
      were derived from the genomes of their hosts. Here we examine molecular
      phylogenies of key DNA repair enzymes in light of recent hypotheses on the origin
      of Megavirales, and propose that the last common ancestors of the individual
      families of the order Megavirales already possessed DNA repair functions to
      achieve and maintain a moderately large genome and that this repair capacity
      gradually increased, in a family-dependent manner, during their recent evolution.

PMID- 27042992
TI  - The folding landscape of the epigenome.
AB  - The role of the spatial organization of chromatin in gene regulation is a long
      standing but still open question. Experimentally it has been shown that the
      genome is segmented into epigenomic chromatin domains that are organized into
      hierarchical sub-nuclear spatial compartments. However, whether this non-random
      spatial organization only reflects or indeed contributes-and how-to the
      regulation of genome function remains to be elucidated. To address this question,
      we recently proposed a quantitative description of the folding properties of the
      fly genome as a function of its epigenomic landscape using a polymer model with
      epigenomic-driven attractions. We propose in this article, to characterize more
      deeply the physical properties of the 3D epigenome folding. Using an efficient
      lattice version of the original block copolymer model, we study the structural
      and dynamical properties of chromatin and show that the size of epigenomic
      domains and asymmetries in sizes and in interaction strengths play a critical
      role in the chromatin organization. Finally, we discuss the biological
      implications of our findings. In particular, our predictions are quantitatively
      compatible with experimental data and suggest a different mean of self
      interaction in euchromatin versus heterochromatin domains. 

PMID- 27042993
TI  - WITHDRAWN: Laser resurfacing for facial acne scars.

PMID- 27042994
TI  - Simvastatin Reduces Cancerogenic Potential of Renal Cancer Cells via
      Geranylgeranyl Pyrophosphate and Mevalonate Pathway.
AB  - Simvastatin is a cholesterol-lowering drug, inhibiting 3-hydroxy-3-methylglutaryl
      coenzyme CoA (HMG-CoA) reductase. Previous studies have indicated the
      anticancerous effects of simvastatin. Here, we evaluated the anticancerous
      potential of simvastatin in renal cell carcinoma (RCC) cell lines. RCC occurs
      with an incidence of 2-3% of all cancer entities with high chemoresistance rate.
      Therefore, the understanding of underlying mechanisms for RCC activity and the
      development of alternative therapies are essential. Human RCC cell lines Caki-1
      and KTC-26 were treated with simvastatin (16 or 33 uM) for 48 or 72 h. The
      effects of the downstream substrates mevalonate (MA), farnesyl pyrophosphate
      (FPP), and geranylgeranyl pyrophosphate (GGPP) were evaluated using add-back
      experiments. Cell growth was assessed using MTT assay. Apoptosis and cell cycle
      were analyzed by flow cytometry. Apoptosis-involved proteins were evaluated by
      Western blot. Simvastatin caused dose- and time-dependent inhibition of RCC cell
      growth by cell cycle arrest and apoptosis induction. Substitution of MA or GGPP
      abolished these effects to a large extent. These findings suggest that the
      antiproliferative effects of simvastatin are not only mediated through
      cholesterol deprivation but also by prenylation-associated mechanisms, thereby
      providing new insights into tumor-suppressive ability of simvastatin and into
      novel additive treatment options in the management of RCC.

PMID- 27042995
TI  - Challenges facing contemporary preimplantation genetic screening.
AB  - PURPOSE OF REVIEW: Aneuploidy is a leading cause of pregnancy failure. Although
      initial attempts to perform preimplantation genetic screening did not improve
      outcomes, validated techniques were developed to safely and effectively increase
      pregnancy rates. Still, many embryos designated as euploid do not implant.
      Current approaches are being refined to provide additional biologic insight into
      why this is the case. At present, the diagnosis and clinical relevance of
      segmental aneuploidy and mosaicism are amongst the more heavily investigated.
      RECENT FINDINGS: Class I data have proven the safety of trophectoderm biopsy and
      validation studies have shown single nucleotide polymorphism array and
      quantitative PCR can accurately detect whole chromosome aneuploidy. Similar
      studies to validate next generation sequencing are underway. Although randomized
      control trials have demonstrated the clinical utility of preimplantation genetic
      screening, recent data on the impact of mosaicism and segmental aneuploidy
      require clarification. SUMMARY: Several well powered randomized control trials
      have shown preimplantation genetic screening improves implantation rate.
      Plausible explanations for euploid failures include undetected mosaicism and
      segmental aneuploidy. However, the true incidence and dispersion of mosaicism
      within the embryo is unknown. Likewise, the resolution of detection and clinical
      significance of segmental aneuploidy is unclear. Further research to validate
      proposed detection algorithms and class I data to determine if detection impacts
      outcomes is needed.

PMID- 27042996
TI  - Nanocomposites: general discussion.

PMID- 27042997
TI  - How cocrystals of weakly basic drugs and acidic coformers might modulate
      solubility and stability.
AB  - Cocrystals of a weakly basic drug (nevirapine) with acidic coformers are shown to
      alter the solubility dependence on pH, and to exhibit a pHmax above which a less
      soluble cocrystal becomes more soluble than the drug. The cocrystal solubility
      advantage can be dialed up or down by solution pH. 

PMID- 27042998
TI  - Initial Weekly HRV Response is Related to the Prospective Change in VO2max in
      Female Soccer Players.
AB  - The aim of this study was to determine whether the early response in weekly
      measures of HRV, when derived from a smartphone application, were related to the
      eventual change in VO2max following an off-season training program in female
      soccer athletes. 9 female collegiate soccer players participated in an 11-week
      off-season conditioning program. In the week immediately before and after the
      training program, each participant performed a test on a treadmill to determine
      maximal oxygen consumption (VO2max). Daily measures of the log-transformed root
      mean square of successive R-R intervals (lnRMSSD) were performed by the
      participants throughout week 1 and week 3 of the conditioning program. The mean
      and coefficient of variation (CV) lnRMSSD values of week 1 showed small (r=-
      0.13, p=0.74) and moderate (r=0.57, p=0.11), respectively, non-significant
      correlations to the change in VO2max at the end of the conditioning program
      (?VO2max). Significant and near-perfect correlation was found between the change
      in the weekly mean lnRMSSD values from weeks 1 and 3 (?lnRMSSDM) and ?VO2max
      (r=0.90, p=0.002). The current results have identified that the initial change in
      weekly mean lnRMSSD from weeks 1 to 3 of a conditioning protocol was strongly
      associated with the eventual adaptation of VO2max. 

PMID- 27042999
TI  - Effects of Varied Versus Constant Loading Zones on Muscular Adaptations in
      Trained Men.
AB  - The purpose of this study was to compare the effects of a protocol employing a
      combination of loading zones vs. one employing a constant medium-repetition
      loading zone on muscular adaptations in resistance-trained men. 19 trained men
      (height=176.9+/-7.0 cm; body mass=83.1+/-11.8 kg; age=23.3+/-2.9 years) were
      randomly assigned to 1 of 2 experimental groups: a constant-rep resistance
      training (RT) routine (CONSTANT) that trained using 8-12 RM per set, or a varied
      rep RT routine (VARIED) that trained with 2-4 RM per set on Day 1, 8-12 RM per
      set on Day 2, and 20-30 RM on Day 3 for 8 weeks. Results showed that both groups
      significantly increased markers of muscle strength, muscle thickness, and local
      muscular endurance, with no differences noted between groups. Effect sizes
      favored VARIED over CONSTANT condition for elbow flexor thickness (0.72 vs.
      0.57), elbow extensor thickness (0.77 vs. 0.48), maximal bench press strength
      (0.80 vs. 0.57), and upper body muscle endurance (1.91 vs. 1.28). In conclusion,
      findings indicate that both varied and constant loading approaches can promote
      significant improvements in muscular adaptations in trained young men. 

PMID- 27043000
TI  - Diagnostic and Therapeutic Challenges.

PMID- 27043001
TI  - An attempt to predict tooth crown height using cementoenamel junction diameters
      and implications in the quantitative study of dental wear.
AB  - SUMMARY: Dental wear has been used extensively in osteoarchaeological studies as
      a means of exploring dietary patterns and the use of teeth as tools. The present
      paper aims to test whether crown height can be predicted for premolars and molars
      based on the mesiodistal and buccolingual diameters of these teeth at the level
      of the cementoenamel junction (CEJ). Multiple linear regression was used with
      crown height as dependent variable and diameters at the CEJ as predictors. Our
      results found that there are cases where the impact of one predictor appears to
      be statistically significant. However, even in these cases the 95% confidence
      interval for the predicted value is so broad that makes the accurate
      determination of the crown height based on the buccolingual or/and mesiodistal
      diameters at the CEJ impossible.

PMID- 27043002
TI  - Near-optimal probabilistic RNA-seq quantification.
AB  - We present kallisto, an RNA-seq quantification program that is two orders of
      magnitude faster than previous approaches and achieves similar accuracy. Kallisto
      pseudoaligns reads to a reference, producing a list of transcripts that are
      compatible with each read while avoiding alignment of individual bases. We use
      kallisto to analyze 30 million unaligned paired-end RNA-seq reads in <10 min on a
      standard laptop computer. This removes a major computational bottleneck in RNA
      seq analysis.

PMID- 27043003
TI  - Shame and Blame in the Therapeutic Relationship.

PMID- 27043004
TI  - Severe Meningoencephalitis in a Case of Ebola Virus Disease: A Case Report.

PMID- 27043005
TI  - Olfactory Loss-On the Road to Potential Diagnosis Criteria of Alzheimer Disease.

PMID- 27043006
TI  - Engineered Nanomaterials for Infection Control and Healing Acute and Chronic
      Wounds.
AB  - Nanoengineered biomaterials have dramatically expanded the range of tools used
      for infection control and to accelerate wound healing. This review thoroughly
      describes the developments that are shaping this emerging field and evaluates the
      potential wound healing applications of recently developed engineered
      nanomaterials for both acute and chronic wounds. Specifically, we will assess the
      unique characteristics of engineered nanomaterials that render them applicable
      for wound healing and infection control. A range of engineered nanomaterials,
      including polymeric-, metallic- and ceramic-based nanomaterials, that could be
      used as therapeutic delivery agents to accelerate regeneration of damaged dermal
      and epidermal tissues are also detailed. Finally, we will detail the current
      state of engineered nanomaterials for wound regeneration and will identify
      promising new research directions in infection control.

PMID- 27043007
TI  - Iron (Fe(2+))-Catalyzed Glucosamine Browning at 50  degrees C: Identification and
      Quantification of Major Flavor Compounds for Antibacterial Activity.
AB  - Glucosamine browning at 50  degrees C with (GlcN/Fe(2+)) or without iron (GlcN)
      was studied over time from 0 to 48 h. Generation of reactive oxygen species
      (ROS), H2O2, and (1)O2, along with alpha-dicarbonyls, fructosazine, and
      deoxyfructosazine, was evaluated. Singlet oxygen generation increased over time
      and was greater in GlcN/Fe(2+) caramel solution. The presence of iron
      significantly increased the concentration of alpha-dicarbonyls at an early
      incubation time (3 h). Fructosazine and deoxyfructosazine were the major
      degradation products at 48 h comprising together up to 37 and 49% in GlcN and
      GlcN/Fe(2+), respectively. GlcN/Fe(2+) (48 h) exhibited a MIC50 against highly
      heat-resistant Escherichia coli AW 1.7 at pH 5, but not at pH 7. Despite several
      antimicrobial compounds being produced during browning, GlcN/Fe(2+) created a
      synergistic environment for the fructosazine-organic acids to confer their
      antimicrobial activity. GlcN caramel solutions have the potential to serve as
      both flavoring compounds and antimicrobial agents in formulated food systems. 

PMID- 27043008
TI  - Solute-Solvent Interactions in Aqueous Solutions of Sulfobutyl Ether-beta
      cyclodextrin As Probed by UV-Raman and FTIR-ATR Analysis.
AB  - A vibrational study by means of UV-Raman and FTIR-ATR measurements has been
      performed on sulfobutyl ether beta-cyclodextrin (SBE-beta-CD)-water solutions, as
      a function of concentration and temperature, with the aim to provide a molecular
      scale explanation of the enhanced performances as carrier agent exhibited by this
      modified macrocycle with respect to natural cyclodextrin. The attention has been
      mainly paid to the modifications induced on the vibrational band assigned to the
      O-H stretching intramolecular mode, in turn related to the dynamical
      rearrangement occurring in the hydrogen bonding (HB) network of water molecules.
      The results of our measurements clearly showed a characteristic "structure
      breaker" effect on the tetrahedral HB arrangements induced on water molecules by
      increasing of both temperature and solute concentration, allowing us to also
      extract thermodynamic parameters. These results could be a key step for a clearer
      understanding of the connection between the dynamical properties of hydration
      water and the complexing ability of this cyclodextrin derivative.

PMID- 27043009
TI  - Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.
AB  - Lipid rafts are thought to be key organizers of membrane-protein complexes in
      cells. Many proteins that interact with rafts have bulky polymeric components
      such as intrinsically disordered protein domains and polysaccharide chains.
      Therefore, understanding the interaction between membrane domains and membrane
      bound polymers provides insights into the roles rafts play in cells. Multiple
      studies have demonstrated that high concentrations of membrane-bound polymeric
      domains create significant lateral steric pressure at membrane surfaces.
      Furthermore, our recent work has shown that lateral steric pressure at membrane
      surfaces opposes the assembly of membrane domains. Building on these findings,
      here we report that membrane-bound polymers are potent suppressors of membrane
      phase separation, which can destabilize lipid domains with substantially greater
      efficiency than globular domains such as membrane-bound proteins. Specifically,
      we created giant vesicles with a ternary lipid composition, which separated into
      coexisting liquid ordered and disordered phases. Lipids with saturated tails and
      poly(ethylene glycol) (PEG) chains conjugated to their head groups were included
      at increasing molar concentrations. When these lipids were sparse on the membrane
      surface they partitioned to the liquid ordered phase. However, as they became
      more concentrated, the fraction of GUVs that were phase-separated decreased
      dramatically, ultimately yielding a population of homogeneous membrane vesicles.
      Experiments and physical modeling using compositions of increasing PEG molecular
      weight and lipid miscibility phase transition temperature demonstrate that longer
      polymers are the most efficient suppressors of membrane phase separation when the
      energetic barrier to lipid mixing is low. In contrast, as the miscibility
      transition temperature increases, longer polymers are more readily driven out of
      domains by the increased steric pressure. Therefore, the concentration of shorter
      polymers required to suppress phase separation decreases relative to longer
      polymers. Collectively, our results demonstrate that crowded, membrane-bound
      polymers are highly efficient suppressors of phase separation and suggest that
      the ability of lipid domains to resist steric pressure depends on both their
      lipid composition and the size and concentration of the membrane-bound polymers
      they incorporate. 

PMID- 27043010
TI  - Synthesis of the C22-C40 Domain of the Azaspiracids.
AB  - An efficient synthesis of the C22-C40 domain of the azaspiracids is described.
      The synthetic route features a Nozaki-Hiyama-Kishi (NHK) coupling and chelation
      controlled Mukaiyama aldol reaction to access an acyclic intermediate and a
      double-intramolecular-hetero-Michael addition (DIHMA) to provide the FG-ring
      system bridged ketal. 

PMID- 27043011
TI  - Identifying Interactions that Determine Fragment Binding at Protein Hotspots.
AB  - Locating a ligand-binding site is an important first step in structure-guided
      drug discovery, but current methods do little to suggest which interactions
      within a pocket are the most important for binding. Here we illustrate a method
      that samples atomic hotspots with simple molecular probes to produce fragment
      hotspot maps. These maps specifically highlight fragment-binding sites and their
      corresponding pharmacophores. For ligand-bound structures, they provide an
      intuitive visual guide within the binding site, directing medicinal chemists
      where to grow the molecule and alerting them to suboptimal interactions within
      the original hit. The fragment hotspot map calculation is validated using
      experimental binding positions of 21 fragments and subsequent lead molecules. The
      ligands are found in high scoring areas of the fragment hotspot maps, with
      fragment atoms having a median percentage rank of 97%. Protein kinase B and
      pantothenate synthetase are examined in detail. In each case, the fragment
      hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a
      fragment-based drug design project.

PMID- 27043012
TI  - Provider Decisions to Treat Respiratory Illnesses with Antibiotics: Insights from
      a Randomized Controlled Trial.
AB  - RATIONALE: Lower respiratory tract illness (LRTI) frequently causes adult
      hospitalization and antibiotic overuse. Procalcitonin (PCT) treatment algorithms
      have been used successfully in Europe to safely reduce antibiotic use for LRTI
      but have not been adopted in the United States. We recently performed a
      feasibility study for a randomized clinical trial (RCT) of PCT and viral testing
      to guide therapy for non-pneumonic LRTI. OBJECTIVE: The primary objective of the
      current study was to understand factors influencing PCT algorithm adherence
      during the RCT and evaluate factors influencing provider antibiotic prescribing
      practices for LRTI. STUDY DESIGN: From October 2013-April 2014, 300 patients
      hospitalized at a community teaching hospital with non-pneumonic LRTI were
      randomized to standard or PCT-guided care with viral PCR testing. Algorithm
      adherence data was collected and multivariate stepwise logistic regression of
      clinical variables used to model algorithm compliance. 134 providers were
      surveyed anonymously before and after the trial to assess knowledge of biomarkers
      and viral testing and antibiotic prescribing practices. RESULTS: Diagnosis of
      pneumonia on admission was the only variable significantly associated with non
      adherence [7% (adherence) vs. 26% (nonadherence), p = 0.01]. Surveys confirmed
      possible infiltrate on chest radiograph as important for provider decisions, as
      were severity of illness, positive sputum culture, abnormal CBC and fever.
      However, age, patient expectations and medical-legal concerns were also at least
      somewhat important to prescribing practices. Physician agreement with the
      importance of viral and PCT testing increased from 42% to 64% (p = 0.007) and 49%
      to 74% (p = 0.001), respectively, after the study. CONCLUSIONS: Optimal algorithm
      adherence will be important for definitive PCT intervention trials in the US to
      determine if PCT guided algorithms result in better outcomes than reliance on
      traditional clinical variables. Factors influencing treatment decisions such as
      patient age, presence of fever, patient expectations and medical legal concerns
      may be amenable to education to improve PCT algorithm compliance for LRTI.

PMID- 27043013
TI  - An Inducible System for Rapid Degradation of Specific Cellular Proteins Using
      Proteasome Adaptors.
AB  - A common way to study protein function is to deplete the protein of interest from
      cells and observe the response. Traditional methods involve disrupting gene
      expression but these techniques are only effective against newly synthesized
      proteins and leave previously existing and stable proteins untouched. Here, we
      introduce a technique that induces the rapid degradation of specific proteins in
      mammalian cells by shuttling the proteins to the proteasome for degradation in a
      ubiquitin-independent manner. We present two implementations of the system in
      human culture cells that can be used individually to control protein
      concentration. Our study presents a simple, robust, and flexible technology
      platform for manipulating intracellular protein levels. 

PMID- 27043014
TI  - Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not
      Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.
AB  - Epidemiological studies have shown that up to one third of adults have
      insufficient levels of vitamin D and there is an association between low vitamin
      D concentrations and adverse brain outcomes, such as depression. Vitamin D has
      been shown to be involved in processes associated with neurogenesis during
      development. Therefore, the aim of this study was to test the hypothesis that
      adult vitamin D (AVD) deficiency in BALB/c mice was associated with (a) adult
      hippocampal neurogenesis at baseline, b) following 6 weeks of voluntary wheel
      running and (c) a depressive-like phenotype on the forced swim test (FST), which
      may be linked to alterations in hippocampal neurogenesis. We assessed
      proliferation and survival of adult born hippocampal neurons by counting the
      number of cells positive for Ki67 and doublecortin (DCX), and incorporation of 5
      Bromo-2'-Deoxyuridine (BrdU) within newly born mature neurons using
      immunohistochemistry. There were no significant effects of diet on number of
      Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly
      increased number of Ki67+ cells and BrdU incorporation, and decreased immobility
      time in the FST, after voluntary wheel running. A significant correlation was
      found in control mice between immobility time in the FST and level of hippocampal
      neurogenesis, however, no such correlation was found for AVD-deficient mice. We
      conclude that AVD deficiency was not associated with impaired proliferation or
      survival of adult born neurons in BALB/c mice and that the impact on rodent
      behaviour may not be due to altered neurogenesis per se, but to altered function
      of new hippocampal neurons or processes independent of adult neurogenesis. 

PMID- 27043015
TI  - Association of MicroRNA-196a2 Variant with Response to Short-Acting beta2-Agonist
      in COPD: An Egyptian Pilot Study.
AB  - Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic
      respiratory disease, characterized by an obstructive pattern. Understanding the
      genetic predisposition of COPD is essential to develop personalized treatment
      regimens. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate
      the expression levels of specific proteins based on sequence complementarity with
      their target mRNA molecules. Emerging evidences demonstrated the potential use of
      miRNAs as a disease biomarker. This pilot study aimed to investigate the
      association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD
      susceptibility, the clinical outcome and bronchodilator response to short-acting
      beta2-agonist. Genotyping of rs11614913 polymorphism was determined in 108 COPD
      male patients and 116 unrelated controls using real-time polymerase chain
      reaction technology. In silico target prediction and network core analysis were
      performed. COPD patients did not show significant differences in the genotype
      distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA
      when compared with controls. There were also no associations with GOLD stage,
      dyspnea grade, disease exacerbations, COPD assessment test for estimating impact
      on health status score, or the frequency of intensive care unit admission.
      However, COPD patients with CC genotype corresponded to the smallest
      bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had
      an intermediate response, while those with the TT genotype showed the highest
      response (p < 0.001). In conclusion MIR-196a2 rs11614913 polymorphism is
      associated with the bronchodilator response of COPD in our sample of the Egyptian
      population, generating hypothesis of the potential use of MIR-196a2 variant as a
      pharmacogenetic marker for COPD. 

PMID- 27043016
TI  - Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years
      in Kampong Cham Communities, Cambodia, 2007-2009.
AB  - BACKGROUND: Leptospirosis is an emerging but neglected public health challenge in
      the Asia/Pacific Region with an annual incidence estimated at 10-100 per 100,000
      population. No accurate data, however, are available for at-risk rural Cambodian
      communities. METHOD: We conducted anonymous, unlinked testing for IgM antibodies
      to Leptospira spp. on paired sera of Cambodian patients <20 years of age between
      2007-2009 collected through active, community-based surveillance for febrile
      illnesses in a convenience sample of 27 rural and semi-rural villages in four
      districts of Kampong Cham province, Cambodia. Leptospirosis testing was done on
      paired serological samples negative for Dengue, Japanese encephalitis and
      Chikungunya viruses after random selection. Convalescent samples found positive
      while initial samples were negative were considered as proof of acute infection.
      We then applied a mathematical model to estimate the risk of fever caused by
      leptospirosis, dengue or other causes in rural Cambodia. RESULTS: A total of 630
      samples are coming from a randomly selected subset of 2358 samples. IgM positive
      were found on the convalescent serum sample, among which 100 (15.8%) samples were
      IgM negative on an earlier sample. Seventeen of these 100 seroconversions were
      confirmed using a Microagglutination Test. We estimated the probability of having
      a fever due to leptospirosis at 1. 03% (95% Credible Interval CI: 0. 95%-1. 22%)
      per semester. In comparison, this probability was 2. 61% (95% CI: 2. 55%, 2. 83%)
      for dengue and 17. 65% (95% CI: 17. 49%, 18. 08%) for other causes. CONCLUSION:
      Our data from febrile cases aged below 20 years suggest that the burden of
      leptospirosis is high in rural Cambodian communities. This is especially true
      during the rainy season, even in the absence of identified epidemics.

PMID- 27043017
TI  - Solid Molecular Phosphine Catalysts for Formic Acid Decomposition in the
      Biorefinery.
AB  - The co-production of formic acid during the conversion of cellulose to levulinic
      acid offers the possibility for on-site hydrogen production and reductive
      transformations. Phosphorus-based porous polymers loaded with Ru complexes
      exhibit high activity and selectivity in the base-free decomposition of formic
      acid to CO2 and H2 . A polymeric analogue of 1,2-bis(diphenylphosphino)ethane
      (DPPE) gave the best results in terms of performance and stability. Recycling
      tests revealed low levels of leaching and only a gradual decrease in the activity
      over seven runs. An applicability study revealed that these catalysts even
      facilitate selective removal of formic acid from crude product mixtures arising
      from the synthesis of levulinic acid.

PMID- 27043018
TI  - An Arginine Deprivation Response Pathway Is Induced in Leishmania during
      Macrophage Invasion.
AB  - Amino acid sensing is an intracellular function that supports nutrient
      homeostasis, largely through controlled release of amino acids from lysosomal
      pools. The intracellular pathogen Leishmania resides and proliferates within
      human macrophage phagolysosomes. Here we describe a new pathway in Leishmania
      that specifically senses the extracellular levels of arginine, an amino acid that
      is essential for the parasite. During infection, the macrophage arginine pool is
      depleted due to its use to produce metabolites (NO and polyamines) that
      constitute part of the host defense response and its suppression, respectively.
      We found that parasites respond to this shortage of arginine by up-regulating
      expression and activity of the Leishmania arginine transporter (LdAAP3), as well
      as several other transporters. Our analysis indicates the parasite monitors
      arginine levels in the environment rather than the intracellular pools.
      Phosphoproteomics and genetic analysis indicates that the arginine-deprivation
      response is mediated through a mitogen-activated protein kinase-2-dependent
      signaling cascade. 

PMID- 27043019
TI  - Initial Diagnosis of ALK-Positive Non-Small-Cell Lung Cancer Based on Analysis of
      ALK Status Utilizing Droplet Digital PCR.
AB  - We describe a novel droplet digital PCR (ddPCR) assay capable of detecting
      genomic alterations associated with inversion translocations. It is applied here
      to detection of rearrangements in the anaplastic lymphoma kinase (ALK) gene
      associated with ALK-positive non-small-cell lung cancer (NSCLC). NSCLC patients
      may carry a nonreciprocal translocation on human chromosome 2, in which
      synchronized double stranded breaks (DSB) within the echinoderm microtubule
      associated protein-like 4 (EML4) gene and ALK lead to an inversion of genetic
      material that forms the non-natural gene fusion EML4-ALK encoding a
      constitutively active tyrosine kinase that is associated with 3 to 7% of all
      NSCLCs. Detection of ALK rearrangements is currently achieved in clinics through
      direct visualization via a fluorescent in situ hybridization (FISH) assay, which
      can detect those rearrangements to a limit of detection (LOD) of ca. 15%. We show
      that the ddPCR assay presented here provides a LOD of 0.25% at lower cost and
      with faster turnaround times.

PMID- 27043020
TI  - ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development.
AB  - ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell
      surface protein with a unique structure possessing both potential adhesion and
      protease domains. However, the role of ADAM10 in preimplantation stage embryos is
      not clear. In this study, we examined the expression patterns and functional
      roles of ADAM10 in porcine parthenotes during preimplantation development. The
      transcription level of ADAM10 dramatically increased from the morula stage
      onward. Immunostaining revealed that ADAM10 was present in both the nucleus and
      cytoplasm in early cleavage stage embryos, and localized to the apical region of
      the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using
      double strand RNA did not alter preimplantation embryo development until morula
      stage, but resulted in significantly reduced development to blastocyst stage.
      Moreover, the KD blastocyst showed a decrease in gene expression of adherens and
      tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by
      disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor,
      GI254023X, at the morula stage also inhibited blastocyst development and led to
      disruption of TJ assembly. An in situ proximity ligation assay demonstrated
      direct interaction of ADAM10 with coxsackie virus and adenovirus receptor
      (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our
      findings strongly suggest that ADADM10 is important for blastocyst formation
      rather than compaction, particularly for TJ assembly and stabilization in
      preimplantation porcine parthenogenetic development. 

PMID- 27043021
TI  - Intermolecular Three-Component Arylsilylation of Alkynes under Palladium/Copper
      Cooperative Catalysis.
AB  - An intermolecular three-component arylsilylation of alkynes has been developed
      under mild palladium/copper cooperative catalysis. The reaction proceeds through
      syn-addition of an aryl group and a silyl group across the carbon-carbon triple
      bond of an alkyne. This represents the first transition-metal-catalyzed fully
      intermolecular arylsilylation of alkynes, and transformations of the resulting
      products have also been demonstrated. 

PMID- 27043022
TI  - Treating hepatitis B virus/hepatitis C virus coinfected patients with direct
      acting hepatitis C virus antivirals only is not safe.

PMID- 27043024
TI  - Reimagining long-term antibiotics in persons who inject drugs: Time to shift the
      status quo?

PMID- 27043023
TI  - Localized sinonasal mucosal melanoma: Outcomes and associations with stage,
      radiotherapy, and positron emission tomography response.
AB  - BACKGROUND: Sinonasal mucosal melanoma is a rare neoplasm with a poor prognosis.
      METHODS: Retrospective analysis was conducted on 78 patients with localized
      sinonasal mucosal melanoma treated at Memorial Sloan Kettering Cancer Center
      (MSKCC from 1998-2013). Demographic, tumor, imaging, and treatment factors were
      recorded and survival and disease-control outcomes were analyzed. RESULTS: Median
      overall survival (OS) and disease-specific survival (DSS) were 32 and 50 months,
      respectively. Median locoregional recurrence-free survival (LRFS) and distant
      recurrence-free survival (DRFS) were 43 and 12 months, respectively. Multivariate
      analysis demonstrated greater OS in nasal cavity tumors and earlier T
      classification. Radiotherapy (RT) was associated with significantly greater LRFS
      (5-years; 35% vs 59%; p = .01), but no difference in OS. Post-RT positron
      emission tomography (PET) response was associated with greater OS. CONCLUSION:
      Distant metastasis is the predominant mode of recurrence in sinonasal mucosal
      melanoma, but local recurrence remains common. RT is associated with improved
      local control, but no survival benefit. The prognostic value of post-RT PET
      imaging warrants further investigation. (c) 2016 Wiley Periodicals, Inc. Head
      Neck 38: 1310-1317, 2016.

PMID- 27043025
TI  - HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type
      2 diabetics.
AB  - BACKGROUND: The aim of the present study was to examine the association between
      variability in HbA1c or systolic blood pressure (SBP) and diabetes-specific
      moderate retinopathy in Asians with type 2 diabetes (T2D). METHODS: A
      retrospective study was conducted of 172 cases of moderate diabetic retinopathy
      (DR) cases and 226 controls without DR, matched for age, sex, and ethnicity.
      Serial HbA1c and SBP (range 3-6 readings) over the 2 years prior to photographic
      screening of DR were collected. Intrapersonal mean and SD values for HbA1c (iM
      HbA1c and iSD-HbA1c) and SBP (iM-SBP and iSD-SBP) were derived. Moderate DR was
      assessed from digital retinal photographs and defined as levels >43 using the
      Early Treatment Diabetic Retinopathy Study scale. RESULTS: Cases of moderate DR
      had higher iM-HbA1c (8.2 % vs 7.3 %; P = 0.001), iSD-HbA1c (1.22 vs 0.64; P =
      0.001), iM-SBP (136.8 vs 129.6 mmHg; P = 0.001) and iSD-SBP (13.3 vs 11.1; P =
      0.002) than controls. In the multivariate regression model adjusted for age,
      gender, ethnicity, duration of diabetes, SBP, and HbA1c, iM-HbA1c and iM-SBP were
      significantly associated with moderate DR (odds ratio [OR] 1.80, 95 % confidence
      interval [CI] 1.37-2.36; and OR 1.03, 95 % CI 1.01-1.05, respectively). Neither
      iSD-HbA1c nor iSD-SBP were associated with moderate DR. When stratified by HbA1c
      <7 %, only iSD-SBP remained significantly associated with moderate DR (OR 1.11,
      95 % CI 1.01-1.21). CONCLUSION: In a cohort of Asian patients with T2D, both
      higher mean HbA1c levels and SBP, but not their variability, were associated with
      moderate DR. Among those with good glycemic control, wider variability of SBP is
      associated with moderate DR.

PMID- 27043027
TI  - Erratum to: Cardiac involvement in systemic sclerosis: differences between
      clinical subsets and influence on survival.

PMID- 27043026
TI  - A lumped parameter model of mechanically mediated acute and long-term adaptations
      of contractility and geometry in lymphatics for characterization of lymphedema.
AB  - A primary purpose of the lymphatic system is to transport fluid from peripheral
      tissues to the central venous system in order to maintain tissue-fluid balance.
      Failure to perform this task results in lymphedema marked by swelling of the
      affected limb as well as geometric remodeling and reduced contractility of the
      affected lymphatic vessels. The mechanical environment has been implicated in the
      regulation of lymphatic contractility, but it is unknown how changes in the
      mechanical environment are related to loss of contractile function and remodeling
      of the tissue. The purpose of this paper was to introduce a new theoretical
      framework for acute and long-term adaptations of lymphatic vessels to changes in
      mechanical loading. This theoretical framework combines a simplified version of a
      published lumped parameter model for lymphangion function and lymph transport, a
      published microstructurally motivated constitutive model for the active and
      passive mechanical behavior of isolated rat thoracic ducts, and novel models for
      acute mechanically mediated vasoreactive adaptations and long-term volumetric
      growth to simulate changes in muscle contractility and geometry of a single
      isolated rat thoracic duct in response to a sustained elevation in afterload. The
      illustrative examples highlight the potential role of the mechanical environment
      in the acute maintenance of contractility and long-term geometric remodeling,
      presumably aimed at meeting fluid flow demands while also maintaining mechanical
      homeostasis. Results demonstrate that contractility may adapt in response to
      shear stress to meet fluid flow demands and show that pressure-induced long-term
      geometric remodeling may attenuate these adaptations and reduce fluid flow. The
      modeling framework and illustrative simulations help suggest relevant experiments
      that are necessary to accurately quantify and predict the acute and long-term
      adaptations of lymphangions to altered mechanical loading.

PMID- 27043028
TI  - Evaluation of pattern electroretinogram in retinal vein occlusion treated with
      intravitreal triamcinolone acetonide.
AB  - PURPOSE: To evaluate pattern electroretinogram (pattern ERG) and anatomical
      changes in optical coherence tomography (OCT) in acute retinal vein occlusion
      with macular oedema after intravitreal triamcinolone acetonide (IVTA) injection.
      METHODS: In this prospective interventional study, 20 patients with acute retinal
      vein occlusion (branch and central) of less than 1 month duration were evaluated
      for pattern ERG, best-corrected visual acuity (BCVA), central macular thickness
      on OCT, and contrast sensitivity (CS) before and 1, 6 and 12 weeks after 1 mg
      IVTA injection. RESULTS: The amplitude of P50 wave (pattern ERG) improved from
      3.01 +/- 1.22 to 3.56 +/- 1.29 uv, mean logMAR BCVA improved from 1.10 +/- 0.60
      to 0.69 +/- 0.45, and CS improved from 0.45 +/- 0.41 to 0.79 +/- 0.29; mean
      central macular thickness (CMT) decreased from 515.35 +/- 202.83 to 358.35 +/-
      135.4u at 12 weeks. All the values were statistically significant (p value <
      0.001). CONCLUSION: IVTA injection in acute retinal vein occlusion with macular
      oedema results in electrophysiological (pattern ERG) improvement in addition to
      anatomical (OCT) improvement.

PMID- 27043029
TI  - Insertion of a single double-J stent for bilateral open ureteral reimplantation:
      introducing a novel technique and assessment of feasibility.
AB  - PURPOSE: To propose a novel technique for bilateral placement of a single double
      J stent during bilateral open ureteral reimplantation in order to reduce the
      intravesical length of stent and potentially minimize the irritative symptoms.
      METHODS: A retrospective chart review was performed to find patients who
      underwent bilateral open ureteral reimplantation. According to the patient's age,
      an appropriate single double-J stent is used for stenting both ureters after open
      reimplantation using the Politano-Leadbetter technique. The stent is fixed to the
      bladder wall with a 4-0 chromic absorbable suture in the midline, superior to the
      intertrigonal ridge. A non-absorbable suture is also fixed to the stent in the
      midline as an extraction string. RESULTS: From June 2009 to July 2013, 20
      patients underwent bilateral ureteric surgery. Twelve (60 %) were female.
      Patients' age ranged from 3 months to 2 years. Double-J stents were successfully
      removed within 2 weeks postoperatively in all patients. CONCLUSIONS: This
      technique might reduce the stent-related symptoms after open bladder surgery for
      bilateral ureteral surgery. Using this technique will reduce the redundant mass
      of ureteral stents in bladder and potentially minimize the trigonal irritation
      and subsequent pain and discomfort.

PMID- 27043030
TI  - GDF-15, iron, and inflammation in early chronic kidney disease among elderly
      patients.
AB  - PURPOSE: The aim of the study was to assess GDF-15 and iron status in patients in
      early stages of chronic kidney disease with a particular emphasis on elderly
      population in association of classic iron status parameters with novel iron
      homeostasis biomarkers and inflammatory parameters. METHODS: Serum concentrations
      of GDF-15, iron (Fe), transferrin saturation, soluble transferrin receptor
      (sTfR), hepcidin, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL
      6), and hemoglobin were measured in 56 patients >=65 years of age and in 31 <65
      years of age. RESULTS: In patients >=65 years, serum concentrations of GDF-15 and
      hsCRP were significantly higher in comparison with younger group. There was no
      statistically significant difference in hemoglobin, iron, hepcidin, and sTfR
      concentration between the two studied groups. In both groups GDF-15 was
      significantly correlated with hemoglobin, eGFR, hsCRP, and IL-6. GDF-15 was
      significantly higher in patients with anemia in comparison with their non-anemic
      counterparts. In multivariate analysis, hemoglobin was found to be a predictor of
      log GDF-15 (beta value = 0.36, P = 0.006, R (2) = 37 %). CONCLUSIONS: An
      intricate interplay between renal function, anemia, and GDF-15 concentrations
      awaits further studies, as there are few data regarding pathophysiological role
      of GDF-15 in diabetes, kidney disease, and other comorbidities. Further
      understanding regarding the signaling pathways of GDF-15 may help to discover
      next pieces in the exciting puzzle of GDF-15. Finally, as studies dealing with
      normal level of GDF-15 in the healthy aged are lacking, it is possible that the
      higher values of GDF-15 values found in the present study represent values of GDF
      15 according to age more than CKD levels.

PMID- 27043031
TI  - Evaluation of Tazobactam-Supplemented, Modified Charcoal-Cefoperazone
      Deoxycholate Agar for Qualitative Detection of Campylobacter from Chicken Carcass
      Rinse.
AB  - Overgrowth of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
      on modified charcoal-cefoperazone-deoxycholate agar (mCCDA) is the most common
      confounding factor for the isolation of Campylobacter from poultry samples. mCCDA
      modified by supplementation with tazobactam, an ESBL inhibitor, was evaluated for
      Campylobacter isolation from chicken carcass rinse with regard to isolation rate
      and selectivity. In total, 120 whole chicken carcasses purchased from retail
      stores were rinsed with buffered peptone water enriched with 2* blood-free Bolton
      broth at 42 degrees C for 48 h and then inoculated onto mCCDA with and without
      tazobactam supplementation (mCCDA or T-mCCDA) at 42 degrees C for 48 h under
      microaerobic conditions. Suspect colonies were subcultured and confirmed by
      colony PCR. Plates with tazobactam exhibited a higher Campylobacter isolation
      rate (56.7% vs. 30.8%, p < 0.05) and selectivity (0.8 vs. 83.3% plates
      contaminated with non-Campylobacter, p < 0.05) than mCCDA. Thus, tazobactam
      supplemented mCCDA would be a useful option for qualitative detection of
      Campylobacter in chicken carcass rinse.

PMID- 27043032
TI  - Aromatic Fused [30] Heteroannulenes with NIR Absorption and NIR Emission:
      Synthesis, Characterization, and Excited-State Dynamics.
AB  - Two hitherto unknown planar aromatic [30] fused heterocyclic macrocycles
      (1.1.0.1.1.0), with NIR absorption in free-base form and protonation-induced
      enhanced NIR emission, have been synthesized from easy to make precursors. The
      induced correspondence of fusion on the macrocyclic structure, electronic
      absorption, and emission spectra have been highlighted.

PMID- 27043033
TI  - Local anesthetic toxicity: Who is ready for lipid resuscitation? A survey of
      German Hospitals.
AB  - PURPOSE: Toxic reactions to local anesthetics are rare but potentially lethal. In
      fact, animal studies and case reports demonstrate that the administration of
      lipid emulsions after initializing cardiopulmonary resuscitation is a promising
      treatment option. The aim of this study was to determine how many hospitals in
      Germany are prepared to treat toxic reactions to local anesthetics with lipid
      infusion and to identify how often and what type of toxic reactions occur and if
      treatment was successful. Further, we aimed to elucidate if current guidelines
      lead to more immediate availability of lipid emulsions in direct proximity to the
      room where regional anesthesia is performed. METHODS: A standardized survey was
      sent to 1,305 German hospitals. The main question was whether lipid emulsions are
      readily available and if published guidelines contributed to this availability.
      Additionally, we asked whether local anesthetic toxicity had already successfully
      been treated by lipid emulsions and what type of symptoms were treated. RESULTS:
      We received replies from n = 509 (39%) hospitals. In 338 (66%) of the responding
      hospitals, lipid emulsions are readily available. Hospitals with standard
      operating procedures (SOPs) implemented according to published guidelines have
      lipids significantly more often immediately available than hospitals with just
      SOPs (chi-square test of independence, p-value < 0.01). Of all responding
      hospitals 287 (56%) have implemented a SOP for the treatment of toxic reactions
      to local anesthetics and 196 (39%) of the hospitals introduced the SOP because of
      the guidelines. In 28 (6%) of the hospitals, local anesthetic toxicity had
      already caused cardiac arrest with subsequent cardiopulmonary resuscitation in at
      least one patient. In 132 (26%) hospitals, local anesthetic toxicity had already
      been treated by infusing lipid emulsions. Of these hospitals 128 (96%) state this
      therapeutic approach was successful. Treatment with lipid emulsions was performed
      frequently after prodromal symptoms 83 (63%) were witnessed. CONCLUSIONS: The
      majority of surveyed German hospitals are prepared to treat toxic reactions to
      local anesthetics and published guidelines contributed to this preparedness. The
      infusion of lipid emulsions is a promising measure to deal with toxic reactions
      to local anesthetics. Since toxic reactions to local anesthetics are potentially
      lethal, it seems desirable that lipid emulsions are generally available in
      routine clinical practice. Currently, the treatment of toxic reactions to local
      anesthetics is mostly performed in situations (e.g. treatment of prodromal
      symptoms) that are not recommended by current guidelines. Further research is
      necessary to better define the future use of lipid emulsions in routine clinical
      practice.

PMID- 27043034
TI  - Virtual car accidents of epilepsy patients, interictal epileptic activity, and
      medication.
AB  - OBJECTIVE: To investigate effects of interictal epileptic activity (IEA) and
      antiepileptic drugs (AEDs) on reactivity and aspects of the fitness to drive for
      epilepsy patients. METHODS: Forty-six adult patients with demonstration of focal
      or generalized bursts of IEA in electroencephalography (EEG) readings within 1
      year prior to inclusion irrespective of medication performed a car driving
      computer test or a single light flash test (39 patients performed both). Reaction
      times (RTs), virtual crashes, or lapses (RT >= 1 s in the car or flash test) were
      measured in an IEA burst-triggered fashion during IEA and compared with RT
      measurements during unremarkable EEG findings in the same session. RESULTS: IEA
      prolonged RTs both in the flash and car test (p < 0.001) in individual patients
      up to 200 ms. Generalized IEA with spike/waves (s/w) had the largest effect on RT
      prolongation (p < 0.001, both tests), whereas mean RT during normal EEG, age,
      gender, and number of AEDs had no effect. The car test was better than the flash
      test in detecting RT prolongations (p = 0.030). IEA increased crashes/lapses >26%
      in sessions with generalized IEA with s/w. The frequency of IEA-associated RT >1
      s exceeded predictions (p < 0.001) based on simple RT shift, suggesting
      functional impairment beyond progressive RT prolongation by IEA. The number of
      AEDs correlated with prolonged RTs during normal EEG (p < 0.021) but not with IEA
      associated RT prolongation or crashes/lapses. SIGNIFICANCE: IEA prolonged RTs to
      varying extents, dependent on IEA type. IEA-associated RTs >1 s were more
      frequent than predicted, suggesting beginning cerebral decompensation of visual
      stimulus processing. AEDs somewhat reduced psychomotor speed, but it was mainly
      the IEA that contributed to an excess of virtual accidents.

PMID- 27043035
TI  - Mass spectrometry in the characterization of reactive metal alkoxides.
AB  - Metal alkoxides are metal-organic compounds characterized by the presence of
      M?O?C bonds (M = metal). Their chemistry seems to be, in principle, relatively
      simple but the number of possible reactant species arising as a consequence of
      their behavior is very remarkable. The physico-chemical properties of metal
      alkoxides are determined by many different parameters, the most important ones
      being the electronegativity of the metal, the ramification of the ligand, and the
      acidity of the corresponding alcohol. Their reactivity makes them suitable and
      versatile candidates for many applications, including homogeneous catalysis,
      synthesis of new ceramic materials through the sol-gel process and, recently,
      also for Cultural Heritage. Metal alkoxides are characterized by a strong
      tendency to give clusters and/or oligomers through oxo-bridges. Mass spectrometry
      has been successfully employed for the characterization of metal alkoxides in the
      gas-phase. Electron ionization (EI) allowed the assessment of the molecular
      weight and of the most relevant decomposition pathways giving information on the
      relative bond strength of differently substituted molecules. On the other hand,
      information on the reactivity in solution of these molecules have been obtained
      by electrospray ionization (ESI)-matrix assisted laser desorption ionization
      (MALDI) experiments performed on their reaction products. These data were
      relevant to investigate the sol-gel process. In this review, these aspects are
      described and the results obtained are critically evaluated. (c) 2016 Wiley
      Periodicals, Inc. Mass Spec Rev.

PMID- 27043036
TI  - The Limitations of Genetic Testing in Psychiatry.

PMID- 27043037
TI  - IgE Reactivity of Recombinant Pac c 3 from the Asian Needle Ant (Pachycondyla
      chinensis).
AB  - BACKGROUND: Stings from the Asian needle ant are an important cause of
      anaphylaxis in East Asia. A 23-kDa protein homologous to antigen 5 is the major
      allergen produced by these ants. In this study, we aimed to produce a recombinant
      antigen 5 allergen, Pac c 3. METHODS: Recombinant Pac c 3 allergen from the Asian
      needle ant was expressed in Pichia pastoris and purified by ammonium sulfate
      precipitation and Ni affinity chromatography. IgE reactivity was demonstrated by
      ELISA and immunoblotting. RESULTS: The recombinant protein was recognized in 5 of
      6 (83.3%) serum samples from patients with demonstrated anaphylaxis to ants. IgE
      reactivity to an antigen 5 allergen from Asian needle ant venom sac extract was
      specifically inhibited by the recombinant protein. It was also able to inhibit
      IgE binding to the vespid allergen Ves v 5 by ImmunoCAP analysis, indicating the
      presence of cross-reactivity. CONCLUSION: A recombinant Pac c 3, cross-reactive
      with Ves v 5, from the Asian needle ant was successfully produced in the
      methylotrophic yeast P. pastoris. This protein could be useful for the
      development of component-resolved diagnostics.

PMID- 27043038
TI  - Plasma-derived exosomes in acute myeloid leukemia for detection of minimal
      residual disease: are we ready?
AB  - The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse
      has introduced the potential for more sensitive non-invasive monitoring of
      leukemia patients based on the molecular and genetic analysis of the exosome
      cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes
      in patients' plasma that associate with leukemic relapse can be identified. The
      diagnostic/prognostic value of these profiles could then be validated in
      prospective clinical studies. Here, we consider the potential of exosomes to
      fulfill the role of future biomarkers of minimal residual disease in AML. The
      rationale for developing exosome-based methodology for minimal residual disease
      detection is based on promising early observations. However, standards need to be
      established for evaluating exosome identity, isolation from body fluids, and
      assessment methods. The rapidly expanding knowledge of the exosome biology
      suggests that the exosome status as potential biomarkers may become clarified in
      the near future.

PMID- 27043039
TI  - Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial
      spin labeling (pCASL): Assessment of relative labeling efficiency at rest and
      during hyperemia, and comparison to pulsed arterial spin labeling (PASL).
AB  - PURPOSE: To compare calf skeletal muscle perfusion measured with pulsed arterial
      spin labeling (PASL) and pseudo-continuous arterial spin labeling (pCASL)
      methods, and to assess the variability of pCASL labeling efficiency in the
      popliteal artery throughout an ischemia-reperfusion paradigm. MATERIALS AND
      METHODS: At 3T, relative pCASL labeling efficiency was experimentally assessed in
      five subjects by measuring the signal intensity of blood in the popliteal artery
      just distal to the labeling plane immediately following pCASL labeling or control
      preparation pulses, or without any preparation pulses throughout separate
      ischemia-reperfusion paradigms. The relative label and control efficiencies were
      determined during baseline, hyperemia, and recovery. In a separate cohort of 10
      subjects, pCASL and PASL sequences were used to measure reactive hyperemia
      perfusion dynamics. RESULTS: Calculated pCASL labeling and control efficiencies
      did not differ significantly between baseline and hyperemia or between hyperemia
      and recovery periods. Relative to the average baseline, pCASL label efficiency
      was 2 +/- 9% lower during hyperemia. Perfusion dynamics measured with pCASL and
      PASL did not differ significantly (P > 0.05). Average leg muscle peak perfusion
      was 47 +/- 20 mL/min/100g or 50 +/- 12 mL/min/100g, and time to peak perfusion
      was 25 +/- 3 seconds and 25 +/- 7 seconds from pCASL and PASL data, respectively.
      Differences of further metrics parameterizing the perfusion time course were not
      significant between pCASL and PASL measurements (P > 0.05). CONCLUSION: No change
      in pCASL labeling efficiency was detected despite the almost 10-fold increase in
      average blood flow velocity in the popliteal artery. pCASL and PASL provide
      precise and consistent measurement of skeletal muscle reactive hyperemia
      perfusion dynamics. J. MAGN. RESON. IMAGING 2016;44:929-939.

PMID- 27043040
TI  - Nationwide survey of specialist knowledge on current standard of care (Peg
      IFN/RBV) and barriers of care in chronic hepatitis C patients in China.
AB  - BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is the leading
      cause of liver diseases including cirrhosis and hepatocellular carcinoma. In
      China, it is a major national health problem that demands nationwide coordinated
      emphasis on prevention and treatment. To inform these initiatives, a nationwide
      survey was conducted from January to April 2015 to evaluate the knowledge,
      awareness, and perceived obstacles to HCV care. METHODS: A sample of 1000 HCV
      specialists across mainland China were recruited. Respondents were asked a series
      of 30 open-ended single or multiple response and Likert-scale questions about
      their HCV treatment knowledge, experience, assessment of HCV care status in
      China, and perceptions about treatment barriers. RESULTS: Sixty percent of the
      respondents answered incorrectly to more than half of the questions on basic HCV
      treatment principles. Over half of them incorrectly believed that maintenance
      therapy should be prescribed for non-responders (72%) and longer treatment
      duration improved sustained viral response rates (62%), regardless of HCV RNA
      level changes. Sixty-six percent of them believed that HCV treatment would still
      be interferon-based therapy in the next 5 years in China. Patient-related
      barriers, in particular lack of disease awareness, were considered to be the most
      significant barriers to HCV care. Payer and medical-provider barriers included
      affordability issues, lack of reimbursement coverage for testing and treatments,
      and lack of referral to HCV specialists. CONCLUSIONS: Focused and intense patient
      and provider education should be carried out to increase awareness. More
      effective direct-acting antivirals should be made available and affordable in
      China.

PMID- 27043041
TI  - Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic
      Patients?
AB  - Mitochondrial fusion/fission alterations have been evaluated in different tissues
      of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial
      dynamics is disturbed in the leukocytes of T2D patients and whether glycemic
      control affects its regulation. Anthropometric and metabolic parameters in 91 T2D
      patients (48 with glycated hemoglobin [HbA1c] <6.5% and 43 with HbA1c >6.5%) were
      characteristic of the disease when compared with 78 control subjects. We observed
      increased reactive oxygen species production in leukocytes from diabetic
      patients, together with a reduced mitochondrial oxygen consumption rate,
      especially in poorly controlled patients. Mitochondrial fusion was reduced and
      fission was increased in diabetic patients, and both features were accentuated in
      patients with poor glycemic control. Furthermore, leukocyte rolling flux rose in
      parallel to HbA1c levels. The induction of leukocyte-endothelial interactions in
      diabetic patients was related to reduced mitochondrial fusion and higher
      mitochondrial fission. Our findings suggest that mitochondrial dynamics could be
      influenced by glycemic control in leukocytes of diabetic patients, in which there
      is decreased mitochondrial fusion and elevated fission related to enhanced
      leukocyte-endothelial interactions. These findings lead to the hypothesis that
      poor glycemic control during T2D may alter mitochondrial dynamics and could
      eventually promote leukocyte-endothelial interactions and the onset of
      cardiovascular diseases. Antioxid. Redox Signal. 25, 108-115.

PMID- 27043042
TI  - "Under the Same Quilt": The Paradoxes of Sex Between Men in the Cultural
      Revolution.
AB  - This article describes the paradoxes experienced by homosexual men during the
      Chinese Cultural Revolution. Interviews with 31 elderly Chinese gay men were
      carried out in four cities in China in 2011. Although homosexual men were
      terribly persecuted, chaotic situations and dislocations of youth from their
      families provided young homosexual men with a remarkable degree of personal
      freedom and the opportunity to explore same-sex relations. Analysis of this
      seemingly contradictory conflation of persecution and freedom will allow us to
      explore the conditions and effects of the coming of age of homosexual men in a
      unique epoch in Chinese history.

PMID- 27043043
TI  - The "neuro" of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder.
AB  - Neuroblastoma is a childhood cancer derived from cells of neural crest origin.
      The hallmarks of its enigmatic character include its propensity for spontaneous
      regression under some circumstances and its association with paraneoplastic
      opsoclonus, myoclonus, and ataxia. The neurodevelopmental underpinnings of its
      origins may provide important clues for development of novel therapeutic and
      preventive agents for this frequently fatal malignancy and for the associated
      paraneoplastic syndromes. Ann Neurol 2016;80:13-23.

PMID- 27043044
TI  - Evaluation of EBV transformation of human memory B-cells isolated by FACS and
      MACS techniques.
AB  - Several studies have been performed to develop effective neutralizing monoclonal
      antibodies. The Epstein-Barr virus (EBV) can efficiently immortalize B-cells to
      establish lymphoblastoid cell lines (LCL) and so it has been used extensively for
      transformation of B-cells to produce and secrete immunoglobulin. The present
      study addressed the effect of TLR7/8 agonist (R848), feeder cells layer and
      fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting
      (MACS) cell separation methods on the transformation efficiency of antibody
      producing memory B-cells. For these studies, the antigen used for analyses of
      antibody formation was the tetanus neurotoxin (TeNT) derived from Clostridium
      tetani. The results here showed that employing an HFFF.PI6 feeder cell layer,
      R848 agonist and FACS-mediated purification of memory B-cells led to increased
      transformation efficiency. Altogether, the effects of the R848 and the feeder
      cells provided an efficient method for EBV transformation of human B-cells.
      Moreover, there was an advantage in using FACS sorting of B-cells over the MACS
      method in the context of EBV transformation and immortalization of precursors of
      antigen-specific B-cells.

PMID- 27043045
TI  - Dapagliflozin in the treatment of patients with type 2 diabetes presenting with
      high baseline A1C.
AB  - OBJECTIVES: To evaluate the efficacy and safety of dapagliflozin 5 and 10 mg/d
      versus placebo in patients with type 2 diabetes and high baseline A1C defined as
      A1C >= 9% or >= 10%. METHODS: A post-hoc analysis was conducted of pooled data
      from 9, 24-week, placebo-controlled clinical studies investigating dapagliflozin
      as monotherapy, add-on therapy to other oral antidiabetes drugs or insulin, or
      initial combination therapy with metformin. RESULTS: At week 24, dapagliflozin 5
      and 10 mg/d decreased A1C (>= 9%: -1.37% and -1.39%, respectively, vs. -0.65%
      with placebo, both P < 0.0001 and >= 10%: -2.13% [P < 0.0001] and -1.59% [P =
      0.0003], respectively, vs. -0.82% with placebo), reduced fasting plasma glucose
      as early as week 1 (P < 0.001 for each dose at all time points for both
      treatments), and decreased body weight (>= 9%: P < 0.0001 vs. placebo for both
      doses; >= 10%: P = 0.0065 vs. placebo, 10 mg/d only). Among patients with
      baseline A1C >= 9% who received dapagliflozin 5 or 10 mg/d, 15.7% and 18.9%,
      respectively, achieved a >= 5% decrease in body weight (both P < 0.0001 vs. 3.6%
      with placebo). Dapagliflozin 10 mg/d decreased systolic and diastolic blood
      pressure (P < 0.0001 and P = 0.0074 vs. placebo). Adverse events were generally
      similar across treatment groups, with the exception of a greater frequency of
      genital infections and hypoglycemia (mostly minor episodes not requiring third
      party assistance) in patients receiving dapagliflozin. CONCLUSION: In patients
      with poorly controlled type 2 diabetes defined as A1C >= 9% or >= 10%,
      dapagliflozin provided clinically meaningful improvements in glycemic parameters,
      body weight, and blood pressure, and was generally well tolerated, making it a
      good therapeutic option for patients with high A1C.

PMID- 27043046
TI  - Consistency of strength curves for determining maximal effort production during
      isokinetic knee testing of anterior cruciate ligament-deficient patients.
AB  - The purpose of this investigation was to attempt to establish decision rules for
      determining maximal effort production during isokinetic strength testing of
      unilateral anterior cruciate ligament-deficient patients based on the degree of
      strength curve consistency within a set. Thirty-three participants performed six
      bilateral knee extension and flexion exertions at maximal effort and at 80% of
      perceived maximum at testing velocities of 60 and 180 degrees s(-1). Within-set
      consistency was quantified by computation of the variance ratio across strength
      curves. Tolerance interval-based cutoff scores covering 99% of the population
      were calculated for declaring efforts as being maximal or not at confidence
      levels of 90%, 95%, and 99%. The sensitivity percentages attained for the injured
      knee for both testing velocities ranged between 9.1% and 27.2%, while specificity
      percentages ranged between 84.8% and 100%. For the non-injured knee, sensitivity
      values for both testing velocities ranged between 21.2% and 45.0%, while
      specificity percentages ranged between 97.0% and 100%. The developed decision
      rules do not effectively discriminate on an individual patient basis between
      maximal and non-maximal isokinetic knee musculature efforts. Further research is
      needed for development of methods that would enable to ascertain maximal effort
      production in this patient population during knee muscle strength testing. 

PMID- 27043048
TI  - Self-efficacy, disability level and physical strength in the injured workers:
      findings from a major factory disaster in Bangladesh.
AB  - INTRODUCTION: In 24 April 2013, Rana Plaza - a high-rise building in Bangladesh
      where garments were being made for the Western markets collapsed. In this study,
      we report on the surviving workers' physical strength, self-efficacy, and
      disability level one year after the disaster. METHODS: This cross-sectional study
      took place at the Centre for the Rehabilitation of the Paralysed (CRP) which
      provided care for more than 600 victims. For this study, upper extremity strength
      among the survivors was assessed by dynamometer hand grip (HG) and lower
      extremity strength by five time sit to stand test (FTSST). The WHODAS tool
      measured level of disability and General Self-Efficacy questionnaire measured
      self-efficacy. Post-traumatic stress disorder (PTSD) prevalence was determined by
      the PCL-scale. RESULTS: The study recruited 181 injured workers. The mean
      disability score among them was 49.8 (SD 17.5) and mean self-efficacy score was
      24.9 (SD 6.9). In multivariate models, after adjusting for age, gender,
      education, injury profile, employment, marital status and job category, self
      efficacy was found to be higher among those who scored above median HG test score
      [beta= -2.32 (95% CI: -4.63, -0.01)] and FTSST performance score [beta= -2.69
      (95% CI: -4.93, -0.46)]. The disability level was found to be significantly
      associated with PTSD score [beta = 0.84 (95% CI: 0.62, 1.06)] and self-efficacy
      score [beta= -0.45 (95% CI: -0.78, -0.13)]. CONCLUSIONS: There is an immense need
      to develop and deliver effective post-injury recovery, rehabilitation and return
      to-work programs for injured workers in resource poor countries. Implications for
      Rehabilitation The study findings suggest that one year after the factory
      disaster in Bangladesh, the injured workers are suffering from a high degree of
      disability, low physical performance and reporting low self-efficacy. The
      national and international stakeholders including Western buyers, aid agencies,
      NGOs, worker advocacy groups, consumer associations and the government of
      Bangladesh can be updated on the progress made so far. There is an immense need
      to develop and deliver effective post-injury recovery, rehabilitation and return
      to-work programs for injured workers in resource poor countries. International
      organizations like ILO, WHO, World Bank can help developing countries in building
      these capacities.

PMID- 27043049
TI  - Chronic hepatitis B and C infection in the United States: a review of current
      guidelines, disease burden and cost effectiveness of screening.
AB  - Chronic hepatitis B and C infection are the leading causes of hepatocellular
      carcinoma and liver related death in the world and in the United States
      respectively. Screening guidelines have been developed based on estimated
      prevalence determined by NHANES data. However, individuals with the most risk of
      chronic infection (incarcerated, homeless, immigrants, nursing home residents,
      and hospitalized persons) are underrepresented in this cohort leading to an
      underestimation of the true prevalence of chronic hepatitis B and C infection.
      This has led to recent updates in the screening guidelines. This review examines
      the change in the guidelines, the likely true seroprevalence of hepatitis B and C
      virus, as well as the burden of chronic infection in this population. 

PMID- 27043050
TI  - Real-life efficacy and safety of ingenol mebutate for the treatment of actinic
      keratosis of the face and scalp: A single arm retrospective study.
AB  - BACKGROUND: The efficacy and safety of ingenol mebutate versus placebo have been
      proven in four randomized controlled trials (RCTs), although there is a lack of
      real-life studies corroborating such promises in routine clinical practices. In
      our study, we sought to describe real-life effectiveness, safety and regimen
      adherence among patients with multiple AKs on the face treated with ingenol
      mebutate and evaluate correlates of clinical outcomes in this population.
      METHODS: We reviewed the clinical charts of adult patients with multiple (>=3) AK
      grade I and II of the face and scalp, treated with ingenol mebutate from April
      2014 to April 2015. All subjects received the medication according to ingenol
      mebutate standard of care. RESULTS: We enrolled 88 patients during the study
      period and carried out 122 treatment cycles. The unadjusted lesion clearance rate
      per treated field was 81.3% and the average local skin reactions score at day 4
      was 6.0 +/- 2.8 (range: 0-18). CONCLUSIONS: We observed an excellent rate (>99%)
      of adherence to ingenol mebutate. This was mirrored by the fact that our clinical
      outcomes broadly confirmed results obtained in RTCs. Our study showed that the
      efficacy and safety of ingenol mebutate observed in RCTs can be reliably
      translated in real-world practice.

PMID- 27043051
TI  - Acute aerobic exercise helps overcome emotion regulation deficits.
AB  - Although colloquial wisdom and some studies suggest an association between
      regular aerobic exercise and emotional well-being, the nature of this link
      remains poorly understood. We hypothesised that aerobic exercise may change the
      way people respond to their emotions. Specifically, we tested whether individuals
      experiencing difficulties with emotion regulation would benefit from a previous
      session of exercise and show swifter recovery than their counterparts who did not
      exercise. Participants (N = 80) completed measures of emotion response
      tendencies, mood, and anxiety, and were randomly assigned to either stretch or
      jog for 30 minutes. All participants then underwent the same negative and
      positive mood inductions, and reported their emotional responses. Analyses showed
      that more perceived difficulty generating regulatory strategies and engaging in
      goal-directed behaviours after the negative mood induction predicted more intense
      and persistent negative affect in response to the stressor, as would be expected.
      Interactions revealed that aerobic exercise attenuated these effects. Moderate
      aerobic exercise may help attenuate negative emotions for participants initially
      experiencing regulatory difficulties. This study contributes to the literature on
      aerobic exercise's therapeutic effects with experimental data, specifically in
      the realm of emotional processing.

PMID- 27043052
TI  - Micro- and nano-mechanics of osteoarthritic cartilage: The effects of tonicity
      and disease severity.
AB  - The present study aims to discover the contribution of glycosaminoglycans (GAGs)
      and collagen fibers to the mechanical properties of the osteoarthritic (OA)
      cartilage tissue. We used nanoindentation experiments to understand the
      mechanical behavior of mild and severe osteoarthritic cartilage at micro- and
      nano-scale at different swelling conditions. Contrast enhanced micro-computed
      tomography (EPIC-MUCT) was used to confirm that mild OA specimens had
      significantly higher GAGs content compared to severe OA specimens. In micro
      scale, the semi-equilibrium modulus of mild OA specimens significantly dropped
      after immersion in a hypertonic solution and at nano-scale, the histograms of the
      measured elastic modulus revealed three to four components. Comparing the peaks
      with those observed for healthy cartilage in a previous study indicated that the
      first and third peaks represent the mechanical properties of GAGs and the
      collagen network. The third peak shows considerably stiffer elastic modulus for
      mild OA samples as compared to the severe OA samples in isotonic conditions.
      Furthermore, this peak clearly dropped when the tonicity increased, indicating
      the loss of collagen (pre-) stress in the shrunk specimen. Our observations
      support the association of the third peak with the collagen network. However, our
      results did not provide any direct evidence to support the association of the
      first peak with GAGs. For severe OA specimens, the peak associated with the
      collagen network did not drop when the tonicity increased, indicating a change in
      the response of OA cartilage to hypertonicity, likely collagen damage, as the
      disease progresses to its latest stages.

PMID- 27043047
TI  - Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery.
AB  - BACKGROUND: Atrial fibrillation after cardiac surgery is associated with
      increased rates of death, complications, and hospitalizations. In patients with
      postoperative atrial fibrillation who are in stable condition, the best initial
      treatment strategy--heart-rate control or rhythm control--remains controversial.
      METHODS: Patients with new-onset postoperative atrial fibrillation were randomly
      assigned to undergo either rate control or rhythm control. The primary end point
      was the total number of days of hospitalization within 60 days after
      randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative
      atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were
      enrolled preoperatively; of these patients, 523 underwent randomization. The
      total numbers of hospital days in the rate-control group and the rhythm-control
      group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There
      were no significant between-group differences in the rates of death (P=0.64) or
      overall serious adverse events (24.8 per 100 patient-months in the rate-control
      group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61),
      including thromboembolic and bleeding events. About 25% of the patients in each
      group deviated from the assigned therapy, mainly because of drug ineffectiveness
      (in the rate-control group) or amiodarone side effects or adverse drug reactions
      (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate
      control group and 97.9% of those in the rhythm-control group had had a stable
      heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and
      84.2% and 86.9%, respectively, had been free from atrial fibrillation from
      discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and
      rhythm control to treat postoperative atrial fibrillation were associated with
      equal numbers of days of hospitalization, similar complication rates, and
      similarly low rates of persistent atrial fibrillation 60 days after onset.
      Neither treatment strategy showed a net clinical advantage over the other.
      (Funded by the National Institutes of Health and the Canadian Institutes of
      Health Research; ClinicalTrials.gov number, NCT02132767.).

PMID- 27043053
TI  - The isolation and identification of new microalgal strains producing oil and
      carotenoid simultaneously with biofuel potential.
AB  - Taxonomy and phylogeny of twenty two microalgal isolates were examined using both
      universal and newly designed molecular primers. Among the isolates, Scenedesmus
      bijugus, Coelastrella sp., Auxenochlorella protothecoides, and Chlorella sp. were
      particularly promising in terms of producing lipids as measured by fatty acid
      methyl esters (FAME) analysis and significant concentration of carotenoids. A
      comparative experiment showed that S. bijugus and Chlorella sp. were the most
      promising candidates (L(-)(1)d(-)(1), with biomass) 174.77+/-6.75, 169.81+/
      5.22mg, lipids 40.14+/-3.31, 39.72+/-3.89mg, lutein 0.47, 0.36mg, and astaxanthin
      0.27, 0.18mg respectively. The fatty acids produced by these microalgal isolates
      were mainly palmitic, stearic, oleic, linoleic, and linolenic acid. The
      freshwater microalgal isolate S. bijugus be the most suitable isolate for
      producing biodiesel and carotenoids, due to high productivity of biomass, lipids,
      metabolites, and its suitable fatty acid profile. 

PMID- 27043054
TI  - Successful start-up of the anammox process: Influence of the seeding strategy on
      performance and granule properties.
AB  - Successful start-up of the anaerobic ammonium oxidation (anammox) process in up
      flow sludge blanket reactor was achieved by seeding denitrifying (R0) or mixed
      denitrifying-anammox granular sludge at a 3:1 volume ratio (R1). The results
      demonstrated that R1 was successfully started-up on day 40 and had a nitrogen
      removal rate (NRR) of 0.55kgNm(-3)d(-1). By contrast, it took 98days to start up
      R0 (0.54kgNm(-3)d(-1)). R0 and R1 achieved maximum NRRs of 5.70 and 12.02kgNm(
      3)d(-1), respectively. The biogranules from R1 generally possessed greater
      specific anammox activity (SAA), higher extracellular polymeric substance (EPS)
      and heme c content, larger granules and greater settling velocity. Quantitative
      PCR (qPCR) and high-throughput sequencing techniques were used to monitor the
      evolution of the bacterial community. These results demonstrated the feasibility
      of seeding mixed denitrifying-anammox granular sludge to start-up an anammox
      reactor. 

PMID- 27043055
TI  - Evaluation of ferric oxide and ferric citrate for their effects on fermentation,
      production of sulfide and methane, and abundance of select microbial populations
      using in vitro rumen cultures.
AB  - This study systematically evaluated the effect of ferric iron on sulfate
      reduction to sulfide, feed digestion and fermentation, methane production, and
      populations of select ruminal microbes using in vitro rumen cultures. Ferric
      oxide (Fe2O3) and ferric citrate (C6H5FeO7) at six concentrations (0, 25, 50,
      100, 150, and 200mg/L as Fe(3+)) were tested. Ferric iron decreased production of
      both H2S gas in culture headspace (up to 71.9%) and aqueous sulfide (up to
      80.8%), without adversely affecting other fermentation parameters, with ferric
      citrate being more effective than ferric oxide. Total archaeal population was
      increased by ferric citrate, but methane production was not affected
      significantly. The population of sulfate reducing bacteria was affected
      differently by ferric oxide than by ferric citrate. The results of this study
      could guide future in vivo studies to develop effective solutions to abate sulfur
      associated polioencephalomalacia in cattle fed high-sulfur diet such as dried
      distiller's grains with solubles. 

PMID- 27043056
TI  - A regulating method for the distribution of phosphorus fractions based on
      environmental parameters related to the key phosphate-solubilizing bacteria
      during composting.
AB  - This study was conducted to assess the abundance, incidence and diversity of the
      culturable phosphate-solubilizing bacteria (PSB) community during different
      organic wastes composting. The key PSB affecting different phosphorus (P)
      fractions and their relationship with environmental variables were analyzed by
      redundancy analysis (RDA). The results showed that there were distinct
      differences in amounts, incidence and community composition of PSB for the
      composts from different sources. Regression analysis demonstrated significant
      corrections between the density and incidence of PSB and pH, temperature, OM and
      DOC/DON. Most of culturable PSB showed high percentages of identity with the
      phyla of Firmicutes and Proteobacteria. There were thirteen key PSB correlated
      closely (p<0.05) with different P fractions variation. Conclusively, we suggested
      a process control method to regulate the distribution of P fractions during
      composting based on the relationship between the key PSB and P fractions as well
      as environmental parameters. 

PMID- 27043057
TI  - Heterotrophic nitrogen removal by a newly-isolated alkalitolerant microorganism,
      Serratia marcescens W5.
AB  - A new microbe, Serratia marcescens W5 was successfully isolated. Its feasibility
      in purification of excessively nitrogen-containing wastewater was evaluated using
      inorganic nitrogen media. Single factor tests showed that W5 exhibited high
      ammonium removal rates (above 80%) under different culture conditions (pH 7-10,
      C/N ratios of 6-20, 15-35 degrees C, 0-2.5% of salinity, respectively). Besides
      various organic carbon sources, W5 was able to utilize calcium carbonate with
      28.05% of ammonium removed. Further experiments indicated that W5 was capable of
      resisting high-strength ammonium (1200mg/L) with the maximum removal rate of
      514.13mgL(-1)d(-1). The nitrogen removal pathway of W5 was also tested, showing
      that both nitrite and nitrate were efficiently removed only in the presence of
      ammonium, with hydroxylamine as intermediate, which was different from the
      conventional nitrogen removal pathway. All the results verified that W5 was a
      good candidate for the purification of excessively nitrogenous wastewater. 

PMID- 27043058
TI  - Ultraviolet safety assessments of insect light traps.
AB  - Near-ultraviolet (UV-A: 315-400 nm), "black-light," electric lamps were invented
      in 1935 and ultraviolet insect light traps (ILTs) were introduced for use in
      agriculture around that time. Today ILTs are used indoors in several industries
      and in food-service as well as in outdoor settings. With recent interest in
      photobiological lamp safety, safety standards are being developed to test for
      potentially hazardous ultraviolet emissions. A variety of UV "Black-light" ILTs
      were measured at a range of distances to assess potential exposures. Realistic
      time-weighted human exposures are shown to be well below current guidelines for
      human exposure to ultraviolet radiation. These UV-A exposures would be far less
      than the typical UV-A exposure in the outdoor environment. Proposals are made for
      realistic ultraviolet safety standards for ILT products. 

PMID- 27043059
TI  - Coronary angiography and myocardial revascularization following the first acute
      myocardial infarction in Norway during 2001-2009: Analyzing time trends and
      educational inequalities using data from the CVDNOR project.
AB  - BACKGROUND: We analyzed trends in the utilization of coronary angiography and
      revascularization - including percutaneous coronary intervention (PCI) or
      coronary artery bypass surgery (CABG) - related to the first AMI and explored
      potential educational inequalities in such procedures. METHODS AND RESULTS: All
      first AMI patients aged 35-89, hospitalized during 2001-2009 were retrieved from
      'The Cardiovascular Disease in Norway' project. Information on education was
      obtained from The Norwegian Education Database. Gender and age group-specific
      trends in coronary procedures were analyzed using Joinpoint regression.
      Educational inequalities were explored using multivariable Poisson regression and
      reported as incidence rate ratios (IRR). A total of 104 836 patients (37.3%
      women) were included. Revascularization rates increased on average 9.0% and 15.4%
      per year among younger (35-64years) and older (65-89years) men. Corresponding
      increases among women were 5.6% and 16.6%. Compared to patients with primary
      education only, those with secondary and tertiary education had 8% (IRR=1.08, 95%
      CI; 1.06-1.10) and 12% (IRR=1.12, 95% CI; 1.09-1.14) higher revascularization
      rates. Educational inequalities were entirely driven by educational differences
      in receiving coronary angiography (IRR=1.10, 95% CI; 1.08-1.11 for secondary
      versus primary and IRR=1.14, 95% CI; 1.12-1.16 for tertiary versus primary
      education level.) Among diagnosed patients, no educational differences were
      observed in coronary revascularization rates. CONCLUSION: Revascularization rates
      increased whereas educational differences in revascularization decreased among
      AMI patients in Norway during 2001-2009. Lower coronary revascularization rates
      among patients with low education were explained by educational differences in
      receiving coronary angiography.

PMID- 27043060
TI  - Comparison of linear versus cubic assessment of left atrial size in the
      prediction of atrial fibrillation development in hypertrophic cardiomyopathy.

PMID- 27043061
TI  - Risk of heart failure with dipeptidyl peptidase-4 inhibitors in patients with
      type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

PMID- 27043062
TI  - An oxidative stress biomarker, urinary 8-hydroxy-2'-deoxyguanosine, predicts
      cardiovascular-related death after steroid therapy for patients with active
      cardiac sarcoidosis.
AB  - BACKGROUND: We investigated whether urinary 8-hydroxy-2'-deoxyguanosine (U-8
      OHdG), a marker of oxidative DNA damage, is a prognosticator of cardiovascular
      related death in patients with cardiac sarcoidosis (CS). METHODS AND RESULTS: In
      this prospective study, 30 consecutive patients were divided into the active CS
      (n=20) and non-active CS (n=10) groups, based on abnormal isotope accumulation in
      the heart on (18)F-fluorodeoxyglucose positron-emission tomography/computed
      tomography ((18)F-FDG PET/CT) imaging. Nineteen patients in the active CS group
      underwent corticosteroid therapy. Before corticosteroid therapy initiation, U-8
      OHdG, brain natriuretic peptide (BNP), other biomarkers, and indices of cardiac
      function were measured. Patients were followed-up for a median of 48months. The
      primary endpoint was the incidence of cardiovascular-related death. During the
      follow-up period, in the corticosteroid-treated active CS group, 7 of 19 patients
      experienced cardiovascular-related death. By contrast, in the non-active CS
      group, 1 of 10 patients died from cardiovascular-related causes. Univariate and
      multivariate analyses showed that U-8-OHdG and BNP were independent predictors
      for cardiovascular-related death. The cut-off values for predicting
      cardiovascular death in corticosteroid-treated patients with active CS were
      19.1ng/mg.Cr and 209pg/mL for U-8-OHdG and BNP, respectively. Patients with a U-8
      OHdG concentration >=19.1ng/mg.Cr or a BNP concentration >=209pg/mL had a
      significantly higher cardiovascular-related death risk, but U-8-OHdG had better
      predictive value compared with BNP. CONCLUSION: These findings suggested that U-8
      OHdG was a powerful predictor of cardiovascular-related death in patients with
      CS, suggesting that active CS patients with elevated U-8-OHdG levels might be
      resistant to corticosteroid therapy.

PMID- 27043063
TI  - Heart failure with preserved right ventricular ejection fraction in postoperative
      adults with congenital heart disease: A subtype of severe right ventricular
      pathophysiology.
AB  - BACKGROUND: Right ventricle (RV) may determine heart failure (HF) severity in
      adults with congenital heart disease (ACHD). However, the association of RV
      properties with clinical profiles remains unclear. PURPOSE: To clarify the
      associations of RV properties with biomarkers, exercise capacity, and unscheduled
      hospitalization (USH) in postoperative ACHD patients. METHODS AND RESULTS: We
      evaluated determinants of RV end-diastolic volume (EDVI, ml/m(2)) and pressure
      (EDP, mmHg) in 260 patients who were divided into 4 groups, i.e., those with
      RVEDVI<100 and EDP>=10 (A, n=49, 19%), those with RVEDVI>=100 with EDP>=10 (B,
      n=22), those with RVEDVI<100 and EDP<10 (C, n=134), and those with RVEDVI>=100
      and EDP<10 (D, n=55). EDVI, EDP, and ejection fraction (EF, %) of the RV were
      independently associated with the corresponding value of the left ventricle (LV)
      (p<0.0001 for all). Group A had a RV-EF of 53+/-8 and was defined HF with
      preserved RV-EF (RV-HFpEF). Younger age, lower platelet count, and elevated
      plasma gamma-glutamyltransferase independently predicted the RV-HFpEF. When the
      presence of pulmonary hypertension and LV-HFpEF was included in the analysis,
      these two factors independently predicted the presence of RV-HFpEF (p<0.05
      0.001). On multivariate analysis, older age, number of surgeries, cardiac index,
      and RV systolic pressure independently determined peak oxygen uptake (PVO2,
      p<0.05) and RV outflow reconstruction independently predicted USH. The RV-HFpEF
      group showed the lowest PVO2 and highest incidence of USH among the 4 groups
      (p<0.05). CONCLUSIONS: Impaired RV characteristics, especially RV-HFpEF, with
      liver dysfunction and lower platelet count predicted lower exercise capacity with
      a poorer prognosis in postoperative ACHD patients.

PMID- 27043064
TI  - Cardiac specific titin N2B exon is a novel sensitive serological marker for
      cardiac injury.

PMID- 27043065
TI  - Rebound thrombosis within 24hours after interruption of therapy with rivaroxaban.

PMID- 27043066
TI  - Stabilization mechanisms of oil-in-water emulsions by Saccharomyces cerevisiae.
AB  - A multiphase system is commonly formed during the oil production by microbial
      route, which can lead to stable emulsions hindering product recovery. Thus, this
      study aimed to investigate the mechanisms of emulsion stabilization by the yeast
      Saccharomyces cerevisiae in order to contribute with processes development of oil
      production by fermentation. A model system using hexadecane as oil phase and
      yeast suspension as aqueous phase was used to prepare O/W emulsions. The yeast
      was subjected to different treatments as inactivation (autoclaving) and washing
      before to be resuspended in water. The washing water (water from the first
      washing) and suspension of commercial yeast (active) were also used as aqueous
      phase. After 24h of preparation, the emulsions separated into three phases: top
      (cream), intermediate, and bottom phase. The top or cream phase was a
      concentrated emulsion that kept stable during seven days, except for those
      prepared from washed yeast that were stable only for a short period of time.
      Emulsions prepared with washed yeast showed higher cell adhesion to the droplets
      interface, which implied in a higher amount of yeast into the cream phase in
      comparison to other formulations. Therefore, yeast cells adhesion plays a role on
      emulsion stability, but the greater contribution was provided by cell material
      dispersed into the aqueous phase, regardless of cell viability. 

PMID- 27043067
TI  - Relationship between orexin A and childhood maltreatment in female patients with
      depression and anxiety.
AB  - OBJECTIVE: Childhood maltreatment leads to neuroendocrine changes, which may be
      associated with an increased vulnerability for psychopathology, such as
      depression and anxiety in later life. This study aimed to investigate the
      relationship between childhood maltreatment and orexin A levels in patients with
      depression and anxiety. The study consisted of 27 female outpatients who
      presented with depressive and/or anxiety symptoms, and 27 healthy female
      controls. Childhood trauma history was assessed using the childhood trauma
      questionnaire (CTQ-28) in patients and controls. Serum levels of orexin and
      cortisol were measured in all subjects. There were positive correlations between
      serum orexin levels and CTQ total score and between orexin levels and some CTQ
      subscale scores, such as physical and emotional neglect, in patients. Orexin
      levels in patients with a positive history of physical and emotional neglect were
      higher than those in patients with a negative history of them. In the controls,
      there was a positive correlation between emotional neglect score and serum orexin
      level. There were no differences in serum levels of orexin and cortisol between
      patients and controls. Orexin levels may be associated with childhood
      maltreatment per se, rather than psychopathology, such as depression or anxiety.

PMID- 27043068
TI  - Panax notoginseng saponin is superior to aspirin in inhibiting platelet adhesion
      to injured endothelial cells through COX pathway in vitro.
AB  - OBJECTIVE: This study was designed to investigate the effect of Panax notoginseng
      saponin (PNS) on platelet adhesion to injured endothelial cells (ECs) and
      platelet activation induced by injured ECs, and to explore its underlying
      mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) pretreated
      with aspirin (ASA,15MUg/mL) or PNS (160MUg/mL), or neither, were exposed to
      oxidized low-density lipoprotein (ox-LDL,80mg/L) for 16h. Platelets were then
      added and co-cultured with HUVECs for 5min. Platelet adhesion to ECs, platelet
      CD62p expression, and HUVEC apoptosis were assessed by fluorescence activated
      cell sorting (FACS).Supernatant concentration of 6-keto-PGF1alpha and thromboxane
      2 (TXB2) were measured by radioimmunoassay. Cyclooxygenase-1 (COX-1) and COX-2
      protein expression were measured by western blotting. RESULTS: The inhibitory
      effect of PNS on platelet activation was similar to ASA, but the inhibitory
      effect of PNS on platelet adhesion to ECs was superior to ASA. PNS modulated COX
      2 expression, and increased 6-keto-PGF1alpha concentration in HUVECs, while down
      regulated COX-1 expression and decreased supernatant TXB2 concentration in
      platelets. Co-culturing of injured HUVECs with platelets increased HUVEC
      apoptosis induced by ox-LDL compared with HUVECs cultured without platelets; ASA
      increased HUVEC apoptosis induced by ox-LDL when cultured without platelets,
      while decreased the apoptosis when co-cultured with platelets. CONCLUSIONS: EC
      protection by ASA is closely associated with its inhibitory effect on platelet
      activation. PNS is superior to ASA in protecting ECs and in inhibiting platelet
      adhesion to injured ECs, and the regulation of COX pathway in both ECs and
      platelets might be the underlying mechanisms of PNS.

PMID- 27043069
TI  - Duration of oral contraceptive use and the risk of venous thromboembolism. A case
      control study.
AB  - INTRODUCTION: Oral contraceptive (OC) use increases the risk of venous
      thromboembolism (VTE), but the effect of duration of use remains to be
      elucidated. PATIENTS AND METHODS: This case-control study was aimed to
      investigate the duration of OC use on the risk of VTE according to women age,
      periods of use, prevalence of other risk factors and the role of thrombophilia
      abnormalities. Seven-hundred patients and 209 controls who used OC were
      stratified into short users (<=1year), long users (1 to 5years), and very long
      users (>5years). RESULTS AND CONCLUSIONS: Compared to non-users, the odds ratio
      (OR) for VTE was 9.0 (95% CI 6.9-12.2) in short, 6.5 (95% CI 4.8-83.7) in long
      and 5.9 (95% CI 4.4-8.1) in very long users. The risk of VTE in short users was
      highest in women <=30years and in the first year of use (OR 13.1, 95% CI 7.7
      22.4) and decreased afterward (OR 7.7, 95% CI 5.0-11.9). This trend was not
      observed in women >30years. Compared to non-carriers and non-users, a joint
      effect of thrombophilia abnormalities and OC use on VTE risk was observed
      particularly in short users (OR 62.2, 95% CI 29.8-129.6), but also afterward (OR
      25.4, 95% CI 16.5-39.2). Other transient risk factors for VTE were present in 25%
      of very long and 16% of short users. In conclusion, the risk of VTE in OC users
      decreases over time only before 30years and in first users. Thrombophilia
      abnormalities strongly interact with the duration of OC use in determining VTE.

PMID- 27043070
TI  - Consumer sleep tracking devices: a review of mechanisms, validity and utility.
AB  - Consumer sleep tracking devices such as fitness trackers and smartphone apps have
      become increasingly popular. These devices claim to measure the sleep duration of
      their users and in some cases purport to measure sleep quality and awaken users
      from light sleep, potentially improving overall sleep. Most of these devices
      appear to utilize data generated from in-built accelerometers to determine sleep
      parameters but the exact mechanisms and algorithms are proprietary. The growing
      literature comparing these devices against polysomnography/actigraphy shows that
      they tend to underestimate sleep disruptions and overestimate total sleep times
      and sleep efficiency in normal subjects. In this review, we evaluate the current
      literature comparing the accuracy of consumer sleep tracking devices against more
      conventional methods used to measure sleep duration and quality. We discuss the
      current technology that these devices utilize as well as summarize the value of
      these devices in clinical evaluations and their potential limitations. 

PMID- 27043071
TI  - Sensitivity of African swine fever virus to type I interferon is linked to genes
      within multigene families 360 and 505.
AB  - African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs.
      There are conflicting reports on the role of interferon in ASFV infection. We
      therefore analysed the interaction of ASFV with porcine interferon, in vivo and
      in vitro. Virulent ASFV induced biologically active IFN in the circulation of
      pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes
      from multigene family (MGF) 360 and MGF505, did not. Infection of porcine
      leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels
      of interferon, suggesting a potential source of interferon in animals undergoing
      acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in
      interferon pretreated macrophages and a recombinant virus lacking similar genes
      to those absent in OUR T88/3 was also inhibited. These findings suggest that as
      well as inhibiting the induction of interferon, MGF360 and MGF505 genes also
      enable ASFV to overcome the antiviral state.

PMID- 27043072
TI  - Targeted Imaging of Damaged Bone in Vivo with Gemstone Spectral Computed
      Tomography.
AB  - Achieving high-resolution imaging of bone-cracks and even monitoring them in live
      organisms are of great significance for understanding their extreme biological
      effects but remain quite challenging, especially for adopting commercial imaging
      systems. Herein, we explore the use of the clinical gemstone spectral computed
      tomography (GSCT) technique as a powerful tool for targeted imaging of bone
      cracks in rats via intramuscularly administrating crack-targeted ytterbium-based
      contrast agents (CAs). Material density images of GSCT reveal that bone-cracks
      targeted with CAs can be successfully differentiated from healthy bone based on
      their different X-ray attenuation characteristics, giving GSCT a distinct
      advantage over conventional CT. More importantly, the superior imaging capability
      of GSCT allows us to real-time monitor the targeting and accumulation of CAs
      toward bone-crack in vivo. These results highlight that clinical GSCT, combined
      with ytterbium-based CAs, provides a promising opportunity for understanding bone
      related diseases in the future.

PMID- 27043073
TI  - Alterations of calcium homeostasis in cancer cells.
AB  - Typical hallmarks of cancer include programmed cell death evasion, uncontrolled
      cell growth, invasion, and metastasis. Changes in intracellular Ca(2+) levels can
      modulate signaling pathways that control a broad range of cellular events,
      including those important to tumorigenesis and cancer progression. Here we
      discuss how known molecular mediators of cellular Ca(2+) homeostasis impact tumor
      dynamics and how deregulation of major oncogenes and tumor suppressors is tightly
      associated with Ca(2+) signaling.

PMID- 27043074
TI  - The Face of the Next Generation in China.

PMID- 27043075
TI  - The bulk and the tail of minimal absent words in genome sequences.
AB  - Minimal absent words (MAW) of a genomic sequence are subsequences that are absent
      themselves but the subwords of which are all present in the sequence. The
      characteristic distribution of genomic MAWs as a function of their length has
      been observed to be qualitatively similar for all living organisms, the bulk
      being rather short, and only relatively few being long. It has been an open issue
      whether the reason behind this phenomenon is statistical or reflects a biological
      mechanism, and what biological information is contained in absent words. In this
      work we demonstrate that the bulk can be described by a probabilistic model of
      sampling words from random sequences, while the tail of long MAWs is of
      biological origin. We introduce the concept of a core of a MAW, which are
      sequences present in the genome and closest to a given MAW. We show that in E.
      faecalis, E. coli and yeast the cores of the longest MAWs, which exist in two or
      more copies, are located in highly conserved regions the most prominent example
      being ribosomal RNAs. We also show that while the distribution of the cores of
      long MAWs is roughly uniform over these genomes on a coarse-grained level, on a
      more detailed level it is strongly enhanced in 3' untranslated regions (UTRs)
      and, to a lesser extent, also in 5' UTRs. This indicates that MAWs and associated
      MAW cores correspond to fine-tuned evolutionary relationships, and suggest that
      they can be more widely used as markers for genomic complexity. 

PMID- 27043076
TI  - Glycone-rich Soy Isoflavone Extracts Promote Estrogen Receptor Positive Breast
      Cancer Cell Growth.
AB  - Due to the association of hormone replacement therapy (HRT) with breast cancer
      risk, estrogenically active soy isoflavones are considered as an HRT alternative
      to alleviate menopausal symptoms. However, several recent reports challenged the
      health benefits of soy isoflavones and associated them with breast cancer
      promotion. While glyconic isoflavones are the major constituents of soybean
      seeds, due to their low cell permeability, they are considered to be biologically
      inactive. The glyconic isoflavones may exert their effects on membrane-bound
      estrogen receptors or could be converted to aglycones by extracellular beta
      glucosidases. Therefore, we hypothesized that despite their low cell
      permeability, soybean cultivars with high glyconic isoflavones may promote breast
      cancer cell growth. To test this, composition and estrogenic activity of
      isoflavones from 54 commercial soybean cultivars were determined. Soybean seeds
      produced in identical climate and growth conditions were used to minimize the
      effects of extraneous factors on isoflavone profile and concentrations. The
      glyconic daidzin concentration negatively correlated with genistin and with other
      aglycones. Relative to control, isoflavone extracts from 51 cultivars were
      estrogenic and promoted the growth of estrogen receptor positive (ER+) breast
      cancer cell line MCF-7 from 1.14 to 4.59 folds and other three cultivars slightly
      reduced the growth. Among these, extracts from three cultivars were highly
      estrogenic and promoted MCF-7 cell growth by 2.59-4.64 folds (P<0.005). Among six
      isoflavones, daidzin was positively associated with MCF-7 cell growth (P<0.005, r
      = 0.13966), whereas the negative correlation between genistin and MCF-7 cell
      growth was nearly significant (P<=0.0562, r = -0.026141). Furthermore, in drug
      interaction studies daidzin-rich isoflavone extracts antagonized tamoxifen, an ER
      inhibitor. Taken together, our results suggest that the glyconic daidzin-rich soy
      isoflavone extracts may exert estrogenic effects and promote ER+ breast cancer
      growth.

PMID- 27043077
TI  - Antiretroviral therapy initiation and adherence in rural South Africa: community
      health workers' perspectives on barriers and facilitators.
AB  - South Africa has the largest global HIV/AIDS epidemic, but barriers along the HIV
      care continuum prevent patients from initiating and adhering to antiretroviral
      therapy (ART). To qualitatively explore reasons for poor ART initiation and
      adherence rates from the unique perspective of community health workers (CHWs),
      we conducted focus groups during May-August 2014 with 21 CHWs in rural Msinga,
      KwaZulu-Natal. Interviews were audio-recorded, transcribed, and translated from
      Zulu into English. Hybrid deductive and inductive analytical methods were applied
      to identify emergent themes. Multiple psychosocial, socioeconomic, and socio
      medical barriers acted at the level of the individual, social network, broader
      community, and healthcare environment to simultaneously hinder initiation of and
      adherence to ART. Key themes included insufficient patient education and social
      support, patient dissatisfaction with healthcare services, socioeconomic factors,
      and tension between ART and alternative medicine. Fear of lifelong therapy
      thwarted initiation whereas substance abuse principally impeded adherence. In
      conclusion, HIV/AIDS management requires patient counselling and support
      extending beyond initial diagnosis. Treating HIV/AIDS as a chronic rather than
      acute infectious disease is key to improving ART initiation and long-term
      adherence. Public health strategies include expanding CHWs' roles to strengthen
      healthcare services, provide longitudinal patient support, and foster
      collaboration with alternative medicine providers.

PMID- 27043078
TI  - Laparoscopic versus open distal pancreatectomy for pancreatic cancer.
AB  - BACKGROUND: Surgical resection is currently the only treatment with the potential
      for long-term survival and cure of pancreatic cancer. Surgical resection is
      provided as distal pancreatectomy for cancers of the body and tail of the
      pancreas. It can be performed by laparoscopic or open surgery. In operations on
      other organs, laparoscopic surgery has been shown to reduce complications and
      length of hospital stay as compared with open surgery. However, concerns remain
      about the safety of laparoscopic distal pancreatectomy compared with open distal
      pancreatectomy in terms of postoperative complications and oncological clearance.
      OBJECTIVES: To assess the benefits and harms of laparoscopic distal
      pancreatectomy versus open distal pancreatectomy for people undergoing distal
      pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the
      pancreas, or both. SEARCH METHODS: We used search strategies to search the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      Science Citation Index Expanded and trials registers until June 2015 to identify
      randomised controlled trials (RCTs) and non-randomised studies. We also searched
      the reference lists of included trials to identify additional studies. SELECTION
      CRITERIA: We considered for inclusion in the review RCTs and non-randomised
      studies comparing laparoscopic versus open distal pancreatectomy in patients with
      resectable pancreatic cancer, irrespective of language, blinding or publication
      status.. DATA COLLECTION AND ANALYSIS: Two review authors independently
      identified trials and independently extracted data. We calculated odds ratios
      (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence
      intervals (CIs) using both fixed-effect and random-effects models with RevMan 5
      on the basis of intention-to-treat analysis when possible. MAIN RESULTS: We found
      no RCTs on this topic. We included in this review 12 non-randomised studies that
      compared laparoscopic versus open distal pancreatectomy (1576 participants: 394
      underwent laparoscopic distal pancreatectomy and 1182 underwent open distal
      pancreatectomy); 11 studies (1506 participants: 353 undergoing laparoscopic
      distal pancreatectomy and 1153 undergoing open distal pancreatectomy) provided
      information for one or more outcomes. All of these studies were retrospective
      cohort-like studies or case-control studies. Most were at unclear or high risk of
      bias, and the overall quality of evidence was very low for all reported
      outcomes.Differences in short-term mortality (laparoscopic group: 1/329 (adjusted
      proportion based on meta-analysis estimate: 0.5%) vs open group: 11/1122 (1%); OR
      0.48, 95% CI 0.11 to 2.17; 1451 participants; nine studies; I(2) = 0%), long-term
      mortality (HR 0.96, 95% CI 0.82 to 1.12; 277 participants; three studies; I(2) =
      0%), proportion of people with serious adverse events (laparoscopic group: 7/89
      (adjusted proportion: 8.8%) vs open group: 6/117 (5.1%); OR 1.79, 95% CI 0.53 to
      6.06; 206 participants; three studies; I(2) = 0%), proportion of people with a
      clinically significant pancreatic fistula (laparoscopic group: 9/109 (adjusted
      proportion: 7.7%) vs open group: 9/137 (6.6%); OR 1.19, 95% CI 0.47 to 3.02; 246
      participants; four studies; I(2) = 61%) were imprecise. Differences in recurrence
      at maximal follow-up (laparoscopic group: 37/81 (adjusted proportion based on
      meta-analysis estimate: 36.3%) vs open group: 59/103 (49.5%); OR 0.58, 95% CI
      0.32 to 1.05; 184 participants; two studies; I(2) = 13%), adverse events of any
      severity (laparoscopic group: 33/109 (adjusted proportion: 31.7%) vs open group:
      45/137 (32.8%); OR 0.95, 95% CI 0.54 to 1.66; 246 participants; four studies;
      I(2) = 18%) and proportion of participants with positive resection margins
      (laparoscopic group: 49/333 (adjusted proportion based on meta-analysis estimate:
      14.3%) vs open group: 208/1133 (18.4%); OR 0.74, 95% CI 0.49 to 1.10; 1466
      participants; 10 studies; I(2) = 6%) were also imprecise. Mean length of hospital
      stay was shorter by 2.43 days in the laparoscopic group than in the open group
      (MD -2.43 days, 95% CI -3.13 to -1.73; 1068 participants; five studies; I(2) =
      0%). None of the included studies reported quality of life at any point in time,
      recurrence within six months, time to return to normal activity and time to
      return to work or blood transfusion requirements. AUTHORS' CONCLUSIONS:
      Currently, no randomised controlled trials have compared laparoscopic distal
      pancreatectomy versus open distal pancreatectomy for patients with pancreatic
      cancers. In observational studies, laparoscopic distal pancreatectomy has been
      associated with shorter hospital stay as compared with open distal
      pancreatectomy. Currently, no information is available to determine a causal
      association in the differences between laparoscopic versus open distal
      pancreatectomy. Observed differences may be a result of confounding due to
      laparoscopic operation on less extensive cancer and open surgery on more
      extensive cancer. In addition, differences in length of hospital stay are
      relevant only if laparoscopic and open surgery procedures are equivalent
      oncologically. This information is not available currently. Thus, randomised
      controlled trials are needed to compare laparoscopic distal pancreatectomy versus
      open distal pancreatectomy with at least two to three years of follow-up. Such
      studies should include patient-oriented outcomes such as short-term mortality and
      long-term mortality (at least two to three years); health-related quality of
      life; complications and the sequelae of complications; resection margins;
      measures of earlier postoperative recovery such as length of hospital stay, time
      to return to normal activity and time to return to work (in those who are
      employed); and recurrence of cancer.

PMID- 27043079
TI  - Rapid COJEC Induction Therapy for High-risk Neuroblastoma Patients - Cochrane
      Review.
AB  - BACKGROUND: Neuroblastoma is a rare malignant disease and patients with high-risk
      neuroblastoma have a poor prognosis. Rapid COJEC induction chemotherapy means
      (almost) the same total doses given within a shorter time period. In theory,
      rapid COJEC could reduce the risk of drug resistance and it has been considered
      as a potential candidate for improving the outcome. METHODS: The objective was to
      evaluate effects of rapid COJEC compared to standard induction chemotherapy in
      patients with high-risk neuroblastoma. We searched the databases CENTRAL,
      MEDLINE, and EMBASE from inception to 11 November 2014 and included randomized
      controlled trials. RESULTS: We identified one relevant randomized controlled
      trial with 130 participants receiving rapid COJEC and 132 participants receiving
      standard OPEC/COJEC induction chemotherapy. There was no statistically
      significant difference between the treatment groups in complete response (risk
      ratio 0.99, 95% confidence interval 0.71 to 1.38, P=0.94) and treatment-related
      mortality (risk ratio 1.21, 95% confidence interval 0.33 to 4.39, P=0.77). A
      statistically significant difference in favor of the standard treatment arm was
      identified for the following early toxicities: febrile neutropenia, septicemia,
      and renal toxicity. CONCLUSION: The differences in complete response and
      treatment-related mortality between treatment alternatives were not statistically
      significantly different. Based on the currently available evidence, we are
      uncertain about the effects of rapid COJEC induction chemotherapy in patients
      with high-risk neuroblastoma.

PMID- 27043080
TI  - [Analysis of a Family-centred Care Programme with Follow-up Home-visits in
      Neonatology - In Times of the Directive from G-BA].
AB  - BACKGROUND: Marked progress in neonatology changed care of very preterm infants
      (VLBW) over the last decades - but also the attitude towards family-centred care
      (FCC). With the directive of the German Federal Joined Committee (G-BA),
      politicians recognize the necessity of neonatal FCC. AIM: To evaluate time and
      personnel costs necessary at a centre of established FCC. METHODS: Elternberatung
      "Fruhstart" is a FCC programme for VLBW and seriously ill neonates from
      preganancy at risk to follow-up home-visits delivered by one interdisciplinary
      team. Analysis (2011-2014): 1.) Number of cases /participation in programme, 2.)
      resources of time, 3) and personnel, 4.) funding, 5) economic impact. RESULTS:
      1.1.2011-31.12.2014: 441 cases (total cases: 2 212) participated in the
      programme. Participation of VLBW: mean 92% (86.4-97,2%). Costs of time are
      highest in neonates with congenital malformations: median 13.8 h, VLBW: median
      11,2 h. Transition to home is most time intensive: median 7,3 (0-42.5) h. In
      average of 3.1 full-time nurses (part-time workers) are able to counsel 48
      families/quarter. In severe cases funding is partly provided by health care
      insurances for social medical aftercare: positive applications: mean 92.7% (79.6
      97.7%). CONCLUSION: Participation in the FCC programme in neonatology is high and
      costs of time are manageable.

PMID- 27043081
TI  - Carbon Dioxide Laser Cordotomy as Possible Alternative for Tracheotomy in a
      Neonate with Idiopathic Bilateral Vocal Fold Paralysis.

PMID- 27043083
TI  - Indiscriminate Testing for Heparin-Induced Thrombocytopenia: A Teachable Moment.

PMID- 27043084
TI  - HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and
      promote growth.
AB  - To cope with proteotoxic stress, cells attenuate protein synthesis. However, the
      precise mechanisms underlying this fundamental adaptation remain poorly defined.
      Here we report that mTORC1 acts as an immediate cellular sensor of proteotoxic
      stress. Surprisingly, the multifaceted stress-responsive kinase JNK
      constitutively associates with mTORC1 under normal growth conditions. On
      activation by proteotoxic stress, JNK phosphorylates both RAPTOR at S863 and mTOR
      at S567, causing partial disintegration of mTORC1 and subsequent translation
      inhibition. Importantly, HSF1, the central player in the proteotoxic stress
      response (PSR), preserves mTORC1 integrity and function by inactivating JNK,
      independently of its canonical transcriptional action. Thereby, HSF1
      translationally augments the PSR. Beyond promoting stress resistance, this
      intricate HSF1-JNK-mTORC1 interplay, strikingly, regulates cell, organ and body
      sizes. Thus, these results illuminate a unifying mechanism that controls stress
      adaptation and growth.

PMID- 27043086
TI  - Genetic and epigenetic factors in the regulation of the immune response.
AB  - PURPOSE OF REVIEW: The review will update readers on research examining the
      influence of genetic variation and epigenetics on the immune system and whether
      genetic variation influences the outcome of critically ill children. RECENT
      FINDINGS: Although there have been few recent studies examining the role of
      genetic variation in the severity of disease or outcome in critically ill
      children, studies in critically ill adults have been informative. For example,
      genetic variations in the genes coding for various components of the immune
      response, such as the Toll-like receptor 1, interleukin-1RA, proprotein
      convertase subtilisin/kexin type 9, adoponectin, nuclear factor erythroid 2
      related factor 2, elafin, sphingosine 1-phosphate receptor 3, and sushi, von
      Willebrand factor type A, EGF and pentraxin domain containing 1 have been
      associated with various outcomes in critically ill adult populations. Many of the
      variants demonstrate functional consequences in the protein levels or activities.
      In critically ill children, there is an association with increased ICU length of
      stay in children with septic shock with one of the Toll-like receptor 1 variants.
      SUMMARY: The degree of influence of host genetic variation in the outcome in
      critically ill children remains a much understudied area of research. However, it
      remains important because it may not only help identify children at risk for
      worse outcomes but it may provide insight into mechanisms of critical illnesses
      and novel therapies.

PMID- 27043085
TI  - FAK, talin and PIPKIgamma regulate endocytosed integrin activation to polarize
      focal adhesion assembly.
AB  - Integrin endocytic recycling is critical for cell migration, yet how recycled
      integrins assemble into new adhesions is unclear. By synchronizing endocytic
      disassembly of focal adhesions (FAs), we find that recycled integrins reassemble
      FAs coincident with their return to the cell surface and dependent on Rab5 and
      Rab11. Unexpectedly, endocytosed integrins remained in an active but unliganded
      state in endosomes. FAK and Src kinases co-localized with endocytosed integrin
      and were critical for FA reassembly by regulating integrin activation and
      recycling, respectively. FAK sustained the active integrin conformation by
      maintaining talin association with Rab11 endosomes in a type I
      phosphatidylinositol phosphate kinase (PIPKIgamma)-dependent manner. In migrating
      cells, endocytosed integrins reassembled FAs polarized towards the leading edge,
      and this polarization required FAK. These studies identify unanticipated roles
      for FA proteins in maintaining endocytosed integrin in an active conformation. We
      propose that the conformational memory of endocytosed integrin enhances polarized
      reassembly of FAs to enable directional cell migration.

PMID- 27043087
TI  - Inflammation and innate immune function in critical illness.
AB  - PURPOSE OF REVIEW: The purpose of review is to highlight the inflammatory
      response in critical illness and the importance of immune monitoring and
      modulation in the diagnosis and treatment of critical illness-induced innate
      immune suppression. RECENT FINDINGS: The pro and anti-inflammatory responses are
      known to be concurrently activated in many patients requiring intensive care,
      with innate immune suppression emerging as an important, and potentially
      reversible, complication of critical illness. SUMMARY: The initial inflammatory
      response to critical illness is typically driven by innate immune cells,
      including neutrophils, monocytes, and macrophages. The proinflammatory mediators
      made by these cells are responsible for many of the pathophysiologic features of
      critical illness. Concurrent with this, however, is a compensatory anti
      inflammatory response, including the elaboration of anti-inflammatory mediators
      and impairment of innate immune cell function. This includes reduction of
      monocyte human leukocyte antigen-DR expression and impairment of the ability of
      innate immune cells to produce tumor necrosis factor alpha when stimulated ex
      vivo. In its most severe form this is referred to as immunoparalysis, and is
      associated with markedly increased risks for secondary infection and death in the
      ICU. Prospective testing can detect this phenomenon, and immunostimulatory
      strategies, including the use of granulocyte macrophage-colony stimulating
      factor, have the potential to restore innate immune function in this setting.

PMID- 27043082
TI  - Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With
      Acute Myocardial Infarction: A Randomized Clinical Trial.
AB  - IMPORTANCE: p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation
      is implicated in atherogenesis, plaque destabilization, and maladaptive processes
      in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation
      MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and
      may improve outcomes. OBJECTIVE: To evaluate the efficacy and safety of
      losmapimod on cardiovascular outcomes in patients hospitalized with an acute
      myocardial infarction. DESIGN, SETTING, AND PATIENTS: LATITUDE-TIMI 60, a
      randomized, placebo-controlled, double-blind, parallel-group trial conducted at
      322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A
      consisted of a leading cohort (n = 3503) to provide an initial assessment of
      safety and exploratory efficacy before considering progression to part B
      (approximately 22,000 patients). Patients were considered potentially eligible
      for enrollment if they had been hospitalized with an acute MI and had at least 1
      additional predictor of cardiovascular risk. INTERVENTIONS: Patients were
      randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching
      placebo (n = 1765) on a background of guideline-recommended therapy. Patients
      were treated for 12 weeks and followed up for an additional 12 weeks. MAIN
      OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular
      death, MI, or severe recurrent ischemia requiring urgent coronary
      revascularization with the principal analysis specified at week 12. RESULTS: In
      part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%]
      were women), 99.1% had complete ascertainment for the primary outcome. The
      primary end point occurred by 12 weeks in 123 patients treated with placebo
      (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95%
      CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were
      16.0% with losmapimod and 14.2% with placebo. CONCLUSIONS AND RELEVANCE: Among
      patients with acute MI, use of losmapimod compared with placebo did not reduce
      the risk of major ischemic cardiovascular events. The results of this exploratory
      efficacy study did not justify proceeding to a larger efficacy trial in the
      existing patient population. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT02145468.

PMID- 27043089
TI  - Introduction to Special Issue on Highly Communicable Disease Management.

PMID- 27043088
TI  - Pulmonary hypertension in the premature infant: a challenging comorbidity in a
      vulnerable population.
AB  - PURPOSE OF REVIEW: This review is written from the perspective of the pediatric
      clinician involved in the care of premature infants at risk for pulmonary
      hypertension. The main objective is to better inform the clinician in the
      diagnosis and treatment of pulmonary hypertension in premature infants by
      reviewing the available relevant literature and focusing on the areas for which
      there is the greatest need for continued research. RECENT FINDINGS: Continued
      knowledge regarding the epidemiology of pulmonary hypertension in the premature
      infant population has aided better diagnostic screening algorithms. Included in
      this knowledge, is the association of pulmonary hypertension in infants with
      bronchopulmonary dysplasia (BPD). However, it is also known that beyond BPD, low
      birth weight and other conditions that result in increased systemic inflammation
      are associated with pulmonary hypertension. This information has led to the
      recent recommendation that all infants with BPD should have an echocardiogram to
      evaluate for evidence of pulmonary hypertension prior to discharge from the
      neonatal ICU. SUMMARY: Pulmonary hypertension can be a significant comorbidity
      for premature infants. This review aims to focus the clinician on the available
      literature to improve recognition of the condition to allow for more timely
      interventions.

PMID- 27043090
TI  - Ebola: Urgent Need, Rapid Response.
AB  - STATEMENT: The recent Ebola outbreak brought to bear the true nature of our ever
      shrinking global health care community. Geography can no longer be considered a
      barrier to the spread of a highly communicable disease. Health care providers
      must be prepared to care for these patients regardless of location or
      environment. The simulation community responded rapidly to the Ebola epidemic
      with creative and timely solutions for training and systems optimization.
      Successful programs focused on 2 primary aims. First, the programs equipped the
      health care workers with essential knowledge for caring for their patients and
      protecting themselves. Second, they provided feedback to the system itself,
      identifying gaps in protocol and solutions for logistic challenges these patients
      often present. By having simulation integrated into the patient safety culture of
      our health care systems, we set in place a powerful tool that can respond nimbly
      to a high-stakes threat as evidenced by the success of these Ebola programs.

PMID- 27043091
TI  - Health Worker Focused Distributed Simulation for Improving Capability of Health
      Systems in Liberia.
AB  - INTRODUCTION: The main goal of this study was to produce an adaptable learning
      platform using virtual learning and distributed simulation, which can be used to
      train health care workers, across a wide geographical area, key safety messages
      regarding infection prevention control (IPC). METHODS: A situationally responsive
      agile methodology, Scrum, was used to develop a distributed simulation module
      using short 1-week iterations and continuous synchronous plus asynchronous
      communication including end users and IPC experts. The module contained content
      related to standard IPC precautions (including handwashing techniques) and was
      structured into 3 distinct sections related to donning, doffing, and hazard
      perception training. OUTCOME: Using Scrum methodology, we were able to link
      concepts applied to best practices in simulation-based medical education
      (deliberate practice, continuous feedback, self-assessment, and exposure to
      uncommon events), pedagogic principles related to adult learning (clear goals,
      contextual awareness, motivational features), and key learning outcomes regarding
      IPC, as a rapid response initiative to the Ebola outbreak in West Africa.
      Gamification approach has been used to map learning mechanics to enhance user
      engagement. CONCLUSIONS: The developed IPC module demonstrates how high
      frequency, low-fidelity simulations can be rapidly designed using scrum-based
      agile methodology. Analytics incorporated into the tool can help demonstrate
      improved confidence and competence of health care workers who are treating
      patients within an Ebola virus disease outbreak region. These concepts could be
      used in a range of evolving disasters where rapid development and communication
      of key learning messages are required.

PMID- 27043092
TI  - Rapid Development and Deployment of Ebola Readiness Training Across an Academic
      Health System: The Critical Role of Simulation Education, Consulting, and Systems
      Integration.
AB  - STATEMENT: In this article, we describe an Ebola preparedness initiative with
      implementation across an academic health system. Key stakeholder centers of
      various disciplines and clinical experts collaborated in the development and
      design. Subject matter experts in the areas of Centers for Disease Control and
      Prevention and World Health Organization protocols for personal protective
      equipment donning and doffing conducted initial train-the-trainer sessions for
      program instructors. These trainers represented a cross-section of key clinical
      responders and environmental services. Through a parallel development process, a
      blended learning curriculum consisting of online modules followed by on-site
      training sessions was developed and implemented in both the simulation laboratory
      and the actual clinical care spaces in preparation for a Department of Health
      inspection. Lessons learned included identification of the need for iterative
      refinement based on instructor and trainee feedback, the lack of tolerance of
      practitioners in wearing full-body personal protective equipment for extended
      periods, and the ability of a large system to mount a rapid response to a
      potential public health threat through leveraging of expertise of its Simulation
      Program, Center for Quality, Safety and Innovation as well as a wide variety of
      clinical departments.

PMID- 27043093
TI  - Simulation as a Tool to Facilitate Practice Changes in Teams Taking Care of
      Patients Under Investigation for Ebola Virus Disease in Spain.
AB  - INTRODUCTION: We analyzed the impact of simulation-based training on clinical
      practice and work processes on teams caring for patients with possible Ebola
      virus disease (EVD) in Cantabria, Spain. METHODS: The Government of Spain set up
      a special committee for the management of EVD, and the Spanish Ministry of Health
      and foreign health services created an action protocol. Each region is
      responsible for selecting a reference hospital and an in-house care team to care
      for patients under investigation. Laboratory-confirmed cases of EVD have to be
      transferred to the Carlos III Health Institute in Madrid. Predeployment training
      and follow-up support are required to help personnel work safely and effectively.
      Simulation-based scenarios were designed to give staff the opportunity to
      practice before encountering a real-life situation. Lessons learned by each team
      during debriefings were listed, and a survey administered 3 months later assessed
      the implementation of practice and system changes. RESULTS: Implemented changes
      were related to clinical practice (eg, teamwork principles application), protocol
      implementation (eg, addition of new processes and rewriting of confusing parts),
      and system and workflow (eg, change of shift schedule and rearrangement of room
      equipment). CONCLUSIONS: Simulation can be used to detect needed changes in
      protocol or guidelines or can be adapted to meet the needs of a specific team.

PMID- 27043094
TI  - Use of Simulation to Gauge Preparedness for Ebola at a Free-Standing Children's
      Hospital.
AB  - STATEMENT: On October 10, 2014, a health care worker exposed to Ebola traveled to
      Akron, OH, where she became symptomatic. The resulting local public health
      agencies and health care organization response was unequalled in our region. The
      day this information was announced, the emergency disaster response was activated
      at our hospital. The simulation center had 12 hours to prepare simulations to
      evaluate hospital preparedness should a patient screen positive for Ebola
      exposure. The team developed hybrid simulation scenarios using standardized
      patients, mannequin simulators, and task trainers to assess hospital preparedness
      in the emergency department, transport team, pediatric intensive care unit, and
      for interdepartmental transfers. These simulations were multidisciplinary and
      demonstrated gaps in the system that could expose staff to Ebola. The results of
      these simulations were provided rapidly to the administration. Further simulation
      cycles were used during the next 2 weeks to identify additional gaps and to
      evaluate possible solutions.

PMID- 27043095
TI  - Beating the Spread: Developing a Simulation Analog for Contagious Body Fluids.
AB  - INTRODUCTION: Effective models simulating the spread of contagion from provider
      to other patients, visitors, and rooms in a physically simulated emergency
      department setting have not been reported, and the effect of personal protective
      equipment (PPE) on reducing such spread in a simulated emergency department
      environment has not been quantified. METHODS: We developed a physical model for
      the spread of an Ebola-like virus. The scenario involved 3 computerized
      mannequins. One case was a febrile patient after Ebola exposure. Four residents
      (group A) had only masks and gloves and were initially unaware of exposure
      history, whereas 4 residents (group C) had known exposure history and had full
      PPE present in the room. Infected mannequins and surrounding surfaces were coated
      with Glo Germ, a UV tracer. Fluorescence to UV light was recorded after each
      scenario. Both tracer groups were compared with a control group (group B) in
      which no tracer was used to account for background fluorescence. RESULTS: There
      was transfer of contagion to providers, other patients, nurse and family member
      confederates, and other treatment rooms. Half of group C used full PPE, and half
      used partial PPE. There were 3 contaminations in group C with full PPE use, 15
      contaminations in group C with partial PPE, and 65 contaminations in group A.
      CONCLUSIONS: The UV tracer seems to be a useful analog of contaminated bodily
      fluids because it spread easily and its spread decreased with the use of barrier
      methods. This model could be used in future studies to measure the effectiveness
      of different forms of PPE and to study the effectiveness of provider education on
      appropriately donning and doffing PPE.

PMID- 27043096
TI  - Ebola Virus Disease Simulation Case Series: Patient With Ebola Virus Disease in
      the Prodromal Phase of Illness (Scenario 1), the "Wet" Gastrointestinal Phase of
      Illness (Scenario 2), and the Late, Critically Ill Phase of Disease (Scenario 3).
AB  - INTRODUCTION: As part of an international response to the Ebola virus disease
      (EVD) outbreak, the US Department of Defense has deployed thousands of personnel
      to help train and augment international health care workers. The transmission
      risk of this deadly virus to health care workers has been extreme, demonstrating
      the importance of safe practices while caring for these patients. Medical
      simulation training is well recognized as an integral component for disease
      outbreak preparedness. Therefore, the US Government created a program of
      instruction that outlines a formalized EVD training program, using high-fidelity
      simulation, which projects both an understanding of the disease and its
      transmission risks. METHODS: Two 5-day training courses were established to
      provide training to the 65-member Department of Defense Ebola Response Team,
      which would be activated during a stateside Ebola outbreak. This training
      consisted of Ebola-specific protocols, personal protective equipment
      familiarization, and scenario-based certification for physicians, nurses, and
      public health trainers. Simulation was used to replicate the work environment
      inside an Ebola treatment unit. RESULTS: Three comprehensive clinical scenarios
      covering a wide spectrum of EVD presentations were designed around details of
      published cases to provide the most realistic and relevant EVD training
      available. The authors conducted 10 iterations of the 3 EVD clinical scenarios
      totaling more than 1100 hours of simulation training. CONCLUSIONS: Quality
      practical exercises to include specialized task performance and collective
      teamwork training relied heavily on dedicated facilities and realistic medical
      simulation resulting in valuable lessons learned. In future iterations, these
      characteristics would be imperative to a successful training course.

PMID- 27043097
TI  - Making an "Attitude Adjustment": Using a Simulation-Enhanced Interprofessional
      Education Strategy to Improve Attitudes Toward Teamwork and Communication.
AB  - INTRODUCTION: Health care providers must effectively function in highly skilled
      teams in a collaborative manner, but there are few interprofessional training
      strategies in place. Interprofessional education (IPE) using simulation
      technology has gained popularity to address this need because of its inherent
      ability to impact learners' cognitive frames and promote peer-to-peer dialog.
      Provider attitudes toward teamwork have been directly linked to the quality of
      patient care. Investigators implemented a simulation-enhanced IPE intervention to
      improve staff attitudes toward teamwork and interprofessional communication in
      the emergency department setting. METHODS: The 3-hour course consisted of a
      didactic session highlighting teamwork and communication strategies, 2 simulation
      scenarios on septic shock and cardiac arrest, and structured debriefing directed
      at impacting participant attitudes to teamwork and communication. This was a
      survey-based observational study. We used the TeamSTEPPS Teamwork Attitudes
      Questionnaire immediately before and after the session as a measurement of
      attitude change as well as the Hospital Survey on Patient Safety Culture before
      the session and 1 year after the intervention for program impact at the behavior
      level. RESULTS: Seventy-two emergency department nurses and resident physicians
      participated in the course from July to September 2012. Of the 5 constructs in
      TeamSTEPPS Teamwork Attitudes Questionnaire, 4 had a significant improvement in
      scores-6.4%, 2.8%, 4.0%, and 4.0% for team structure, leadership, situation
      monitoring, and mutual support, respectively (P < 0.0001, P = 0.029, P = 0.014,
      and P = 0.003, respectively). For Hospital Survey on Patient Safety Culture, 3 of
      6 composites directly related to teamwork and communication showed a significant
      improvement-20.6%, 20.5%, and 23.9%, for frequency of event reporting, teamwork
      within hospital units, and hospital handoffs and transitions, respectively (P =
      0.028, P = 0.035, and P = 0.024, respectively). CONCLUSIONS: A simulation
      enhanced IPE curriculum was successful in improving participant attitudes toward
      teamwork and components of patient safety culture related to teamwork and
      communication.

PMID- 27043098
TI  - The Correlation of Workplace Simulation-Based Assessments With Interns' Infant
      Lumbar Puncture Success: A Prospective, Multicenter, Observational Study.
AB  - INTRODUCTION: Little data are available to guide supervisors' decisions regarding
      when trainees are prepared to safely perform their first procedure on a patient.
      We aimed to describe the correlation of simulation-based assessments, in the
      workplace, with interns' first clinical infant lumbar puncture (ILP) success.
      METHODS: This is a prospective, observational subcomponent of a larger study of
      incoming interns at 33 academic medical centers (July 2010 to June 2012)
      assessing the impact of just-in-time training. When an intern's patient required
      an ILP, a just-in-time simulation-based skills refresher was conducted with his
      or her supervisor. At the end of the refresher, supervisors assessed interns' ILP
      skills on a simulator in the workplace before clinical performance using a four
      point anchored scale. The primary outcome was the correlation of supervisors'
      assessment and interns' procedural success. The number needed to assess for this
      instrument (1 / absolute risk reduction) was calculated. RESULTS: A total of 1600
      interns were eligible to participate, and 1215 were enrolled. A total of 297
      completed an assessment and a subsequent clinical ILP. Success rates for each
      scale rating were 29% (18/63) for novice, 39% (51/130) for beginner, 55% (46/83)
      for competent, and 43% (9/21) for proficient. The correlation coefficient was
      0.161 (95% confidence interval, 0.057-0.265), indicating a weak correlation
      between supervisor rating and success. Success rate was 53% for the ratings of
      competent or proficient compared with 35% for the ratings of novice or beginner.
      Using the global rating scale for the summative assessment to determine
      procedural readiness could lead to 1 fewer patient experiencing a failed ILP for
      every 6 interns tested (6.2; 95% confidence interval, 4.0-8.5). CONCLUSIONS: A
      simulation-based assessment of interns conducted in the workplace before their
      first ILP has some value in predicting clinical ILP success.

PMID- 27043099
TI  - Quantitative Feedback Facilitates Acquisition of Skills in Focused Cardiac
      Ultrasound.
AB  - INTRODUCTION: With the development of portable, affordable ultrasound machines
      with good image quality, many physicians have adopted focused cardiac ultrasound
      (FoCUS). To facilitate acquisition of these skills, we developed a simulator
      based, self-taught curriculum for FoCUS that provides immediate feedback for
      rapid performance improvement. METHODS: Twenty-two first-year residents
      participated in the study. The curriculum consisted of instructive modules
      teaching image acquisition and interpretation of standard echocardiography views
      and common cardiac pathology, 7 practice cases in which participants scanned a
      mannequin using a mock transducer, acquired specified views with feedback
      provided by visual guidance technology, and interpreted these images. Trainees
      were tested pretraining and posttraining on different cases, without visual
      guidance assistance or feedback. Previously validated metrics were used to assess
      psychomotor skill in terms of the angle error in degrees between the planes of
      the optimal view, defined anatomically, and of the acquired view, as well as
      cognitive skill in image interpretation. RESULTS: The average error in image
      acquisition decreased from a median of 81 degrees at the pretest to 28 degrees
      after training (P < 0.0001). Cognitive skill improved by 29% (21%, P < 0.0001).
      There was a significant correlation between cognitive and psychomotor skill (r =
      0.64, P < 0.001). DISCUSSION: A novel, simulator-based curriculum that provides
      immediate feedback was effective in teaching both psychomotor and cognitive
      skills in FoCUS without need for direct expert oversight of the learner. The
      curriculum's components provide a useful tool that can be applied to improve,
      assess, and monitor physician skill in FoCUS.

PMID- 27043100
TI  - A Hemodynamic Monitor as a Simulation Tool, a Novel Use of the PiCCO2: Technical
      Description of the Method and Its Application.
AB  - INTRODUCTION: The PiCCO2 is a commonly used monitor, which education remains
      theoretical and demonstration based. Simulation allows active learning, which may
      help achieve a better understanding and handling of this device, hence a safer
      and more effective use. Because of the lack of availability of dedicated
      simulators and the uselessness of the demonstration mode of monitors for
      simulation purpose, simulation remains seldom used. We will describe a novel use
      of the PiCCO2 for simulation training and its experiment in high-fidelity
      simulation (HFS). METHODS: A standard PiCCO2 was modified with software allowing
      its transformation into a simulator. The values displayed on the screen were
      managed in real time by an operator using a standard laptop linked to the monitor
      and using a standard disposable catheter set to execute simulated transpulmonary
      thermodilution. Nineteen volunteers were requested to assess the realism of the
      device during scenarios in which the PiCCO2S (simulator) was used in an HFS
      environment, with a mannequin reproducing a septic shock condition. RESULTS: Two
      experimental sessions were made. PiCCO2S was used in the contextualized setting
      of HFS, which allowed a good interactivity between the device and its users.
      Participants had a positive perception of the realism as well as the method's
      adequacy to achieve a better understanding of the PiCCO2. CONCLUSIONS: The
      PiCCO2S could be obtained from a serial device. Its integration in HFS provided a
      realistic handling of the device. A built-in simulation mode into serial medical
      devices may give users an easy access to training.

PMID- 27043101
TI  - Nonspecific protein labeling of photoaffinity linkers correlates with their
      molecular shapes in living cells.
AB  - Herein we report molecular shape-dependent nonspecific labeling of photoaffinity
      linkers (PLs) in the cellular proteome. Linear PLs have a greater tendency to
      engage in nonspecific binding than branched PLs. Exploiting this property, we
      discovered a smaller branched diazirine-based PL as the best photoaffinity probe
      with minimal nonspecific binding characteristics from among 5 probes with
      different PLs. 

PMID- 27043102
TI  - Stimuli-Responsive Biodegradable Hyperbranched Polymer-Gadolinium Conjugates as
      Efficient and Biocompatible Nanoscale Magnetic Resonance Imaging Contrast Agents.
AB  - The efficacy and biocompatibility of nanoscale magnetic resonance imaging (MRI)
      contrast agents depend on optimal molecular structures and compositions.
      Gadolinium [Gd(III)] based dendritic macromolecules with well-defined and tunable
      nanoscale sizes are excellent candidates as multivalent MRI contrast agents.
      Here, we propose a novel alternate preparation of biodegradable hyperbranched
      polymer-gadolinium conjugates via a simple strategy and report potentially
      efficient and biocompatible nanoscale MRI contrast agents for cancer diagnosis.
      The enzyme-responsive hyperbranched poly(oligo-(ethylene glycol) methacrylate)
      gadolinium conjugate (HB-POEGMA-Gd) was prepared via one-step reversible addition
      fragmentation chain transfer (RAFT) polymerization and Gd(III) chelating, and the
      cRGDyK functionalized polymer (HB-POEGMA-cRGD-Gd) was obtained via click
      chemistry. By using an enzyme similar to lysosomal cathepsin B, hyperbranched
      conjugates of high molecular weights (MW) (180 and 210 kDa) and nanoscale sizes
      (38 and 42 nm) were degraded into low MW (25 and 30 kDa) and smaller products
      (4.8 and 5.2 nm) below the renal threshold. Conjugate-based nanoscale systems had
      three-fold more T1 relaxivity compared to clinical agent
      diethylenediaminepentaacetic acid (DTPA)-Gd. Animal studies with the nanoscale
      system offered greater tumor accumulation and enhanced signal intensity (SI) in
      mouse U87 tumors of which the greatest activity was conferred by the cRGDyK
      moiety functionalized hyperbranched conjugate. In vitro cytotoxicity,
      hemocompatibility and in vivo toxicity studies confirmed no adverse events. This
      design strategy for multifunctional Gd(III)-labeled biodegradable dendritic
      macromolecules may have significant potential as future efficient, biocompatible
      polymeric nanoscale MRI diagnostic contrast agents for cancer.

PMID- 27043105
TI  - Drug-Induced Torsades de Pointes and Genetic Screening.

PMID- 27043106
TI  - Progress Toward Consensus on Breast Cancer Screening Guidelines and Reducing
      Screening Harms.

PMID- 27043107
TI  - Drug-Induced Torsades de Pointes and Genetic Screening--Reply.

PMID- 27043108
TI  - Progress Toward Consensus on Breast Cancer Screening Guidelines and Reducing
      Screening Harms--Reply.

PMID- 27043109
TI  - Association of beta-Blocker Treatment With Adverse Outcomes in Hypertensive
      Patients Undergoing Noncardiac Surgery.

PMID- 27043110
TI  - Association of beta-Blocker Treatment With Adverse Outcomes in Hypertensive
      Patients Undergoing Noncardiac Surgery--Reply.

PMID- 27043111
TI  - Choosing Wisely Recommendations Using Administrative Claims Data.

PMID- 27043112
TI  - Choosing Wisely Recommendations Using Administrative Claims Data.

PMID- 27043113
TI  - Choosing Wisely Recommendations Using Administrative Claims Data.

PMID- 27043114
TI  - Balancing Accelerated Approval for Drugs With Accelerated Withdrawal.

PMID- 27043115
TI  - Choosing Wisely Recommendations Using Administrative Claims Data--Reply.

PMID- 27043116
TI  - Better Training to Control Potential Outbreaks.

PMID- 27043117
TI  - Balancing Accelerated Approval for Drugs With Accelerated Withdrawal--Reply.

PMID- 27043118
TI  - A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of
      Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder.
AB  - This prospective 12-week open-label trial evaluates the tolerability and efficacy
      of memantine hydrochloride for the treatment of core social and cognitive
      deficits in adults with high-functioning autism spectrum disorder (ASD). Measures
      for assessment of therapeutic response included the Social Responsiveness Scale
      Adult Research Version (SRS-A), disorder-specific Clinical Global Impression
      scales, Behavior Rating Inventory of Executive Functioning-Adult Self-Report,
      Diagnostic Analysis of Nonverbal Accuracy Scale, and Cambridge Neuropsychological
      Test Automated Battery. Eighteen adults (mean age, 28 +/- 9.5 years) with high
      functioning ASD (SRS-A raw score, 99 +/- 17) were treated with memantine (mean
      dose, 19.7 +/- 1.2 mg/d; range, 15-20 mg), and 17 (94%) completed the trial.
      Treatment with memantine was associated with significant reduction on informant
      rated (SRS-A, -28 +/- 25; P < 0.001) and clinician-rated (Clinical Global
      Impression-Improvement subscale <=2, 83%) measures of autism severity. In
      addition, memantine treatment was associated with significant improvement in ADHD
      and anxiety symptom severity. Significant improvement was noted in nonverbal
      communication on the Diagnostic Analysis of Nonverbal Accuracy Scale test and in
      executive function per self-report (Behavior Rating Inventory of Executive
      Functioning-Adult Self-Report Global Executive Composite, -6 +/- 8.8; P < 0.015)
      and neuropsychological assessments (Cambridge Neuropsychological Test Automated
      Battery). Memantine treatment was generally well tolerated and was not associated
      with any serious adverse events. Treatment with memantine appears to be
      beneficial for the treatment of ASD and associated psychopathology and cognitive
      dysfunction in intellectually capable adults. Future placebo-controlled trials
      are warranted. 

PMID- 27043119
TI  - Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients
      With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders.
AB  - Adherence to treatment is one of the most consistent factors associated with a
      favorable addiction treatment outcome. Little is known about factors associated
      with treatment adherence in individuals affected with comorbid attention
      deficit/hyperactivity disorder and substance use disorders (SUD). This study
      aimed to explore whether treatment-associated factors, such as the prescribing
      physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related
      factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were
      associated with adherence to MPH treatment. Swedish national registers were used
      to identify adult individuals with prescriptions of MPH and medications
      specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting
      psychiatric diagnoses. Primary outcome measure was days in active MPH treatment
      in stratified dose groups (<=36 mg, >=37 mg to <=54 mg, >=55 mg to <=72 mg, >=73
      mg to <=90 mg, >=91 mg to <=108 mg, and >=109 mg). Lower MPH doses (ie, <=36 mg
      day 100) were associated with treatment discontinuation between days 101 and 830
      (HR<=36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR>=108mg,
      1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of
      treatment discontinuation along with increase of MPH doses. In conclusion, this
      study shows that higher MPH doses were associated with long-term treatment
      adherence in individuals with attention-deficit/hyperactivity disorder and SUD.

PMID- 27043120
TI  - Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of
      Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized,
      Double-Blind, Placebo-Controlled Pilot Study.
AB  - Drug delivery systems capable of delivering free (unconjugated) curcuminoids is
      of great therapeutic significance, since the absorption of bioactive and
      permeable form plays a key factor in mediating the efficacy of a substance which
      undergoes rapid biotransformation. Considering the recent understanding on the
      relatively high bioactivities and blood-brain-barrier permeability of free
      curcuminoids over their conjugated metabolites, the present human study
      investigated the safety, antioxidant efficacy, and bioavailability of CurQfen
      (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin
      with fenugreek dietary fiber that has shown to possess improved blood-brain
      barrier permeability and tissue distribution in rats. In this randomized double
      blinded and placebo-controlled trial, 60 subjects experiencing occupational
      stress-related anxiety and fatigue were randomized to receive CGM, standard
      curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated
      the safety, tolerance, and enhanced efficacy of CGM in comparison with
      unformulated standard curcumin. A significant improvement in the quality of life
      (P < 0.05) with considerable reduction in stress (P < 0.001), anxiety (P <
      0.001), and fatigue (P < 0.001) was observed among CGM-treated subjects as
      compared with the standard curcumin group, when monitored by SF-36, Perceived
      Stress Scale with 14 items, and Beck Anxiety Inventory scores. Improvement in the
      quality of life was further correlated with the significant enhancement in
      endogenous antioxidant markers (P < 0.01) and reduction in lipid peroxidation (P
      < 0.001). Further comparison of the free curcuminoids bioavailability after a
      single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30
      days) oral administration revealed enhanced absorption and improved
      pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1
      fold) administrations. 

PMID- 27043121
TI  - Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on
      the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine.
AB  - Opioid antagonists (eg, naltrexone) and positive modulators of gamma-aminobutyric
      acid type A receptors (eg, alprazolam) each modestly attenuate the abuse-related
      effects of stimulants. A previous study demonstrated that acute pretreatment with
      the combination of naltrexone and alprazolam attenuated a greater number of the
      subject-rated effects of D-amphetamine than the constituent drugs alone. This
      study tested the hypothesis that maintenance on the combination of naltrexone and
      alprazolam XR would attenuate the reinforcing and "positive" subject-rated
      effects of methamphetamine to a greater extent than the constituent drugs
      alone.Eight non-treatment-seeking, stimulant-using individuals completed a
      placebo-controlled, crossover, double-blind inpatient protocol. Participants were
      maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the
      combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6
      to 7 days. Under each maintenance condition, participants sampled intranasal
      doses of methamphetamine (0, 10, and 30 mg), and were then offered the
      opportunity to work for the sampled dose on a modified progressive-ratio
      procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology
      assessments were collected.Intranasal methamphetamine functioned as a reinforcer
      and produced prototypical stimulant-like "positive" subject-rated and
      physiological effects. Maintenance on naltrexone significantly decreased the
      reinforcing, but not subject-rated drug effects of 10-mg methamphetamine.
      Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact
      methamphetamine self-administration or subject-rated drug effects. The results
      support the continued evaluation of naltrexone for methamphetamine dependence, as
      well as the identification of other drugs that enhance its ability to reduce drug
      taking behavior. 

PMID- 27043122
TI  - Paliperidone Palmitate and Metabolic Syndrome in Patients With Schizophrenia: A
      12-Month Observational Prospective Cohort Study.
AB  - Oral and long-acting injectable second-generation antipsychotics are known to be
      associated with a high risk of metabolic adverse effects. Together with other
      drug treatments, poor lifestyle choices, and genetic liability, they contribute
      to development of metabolic syndrome (MetS), which occurs in nearly one third of
      patients with schizophrenia.The primary objective of this multicenter prospective
      observational study was to explore the prevalence of MetS in a sample of 60 real
      world patients treated with paliperidone palmitate (PP) over a period of 12
      months. The secondary objectives were to assess other tolerability aspects and
      the efficacy of PP on schizophrenic symptoms.The proportion of patients with MetS
      at baseline (33%) did not significantly change neither at 6 (39.0%) nor at 12
      months (29.5%) of PP treatment. The same applies to each individual component of
      MetS. We found a slight but statistically significant increase in body mass index
      (26.3 +/- 6.0 vs 27.1 +/- 4.6, P = 0.031) and of waist circumference (98.2 +/-
      17.9 vs 100.3 +/- 15.9, P = 0.021) from baseline to end point. Weight gain was
      detected in approximately 15% of patients.At least 1 mild or moderate adverse
      event was found in 71.3%, 88.0%, and 52.1% of patients, respectively, at
      baseline, 6 months, and 12 months. A significant improvement in schizophrenic
      symptoms emerged by means of Positive and Negative Syndrome Scale total and
      subscale scores.Together with previous literature findings, our results seem to
      indicate that PP could be a valid therapeutic option for patients with a severe
      disorder and with a high metabolic risk profile. 

PMID- 27043123
TI  - Acute Onset of Xanthopsia Associated With Risperidone.

PMID- 27043124
TI  - Atypical Neuroleptic Malignant Syndrome Associated With Paliperidone Long-Acting
      Injection: A Case Report.

PMID- 27043125
TI  - A Case of Chronic Peduncular Hallucinosis in a 90-Year-Old Woman Successfully
      Treated With Olanzapine.

PMID- 27043126
TI  - Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis
      Associated With Clozapine.
AB  - Clozapine use is associated with leukopenia and more rarely agranulocytosis,
      which may be lethal. The drug and its metabolites are proposed to interact with
      the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P
      gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in
      exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes
      in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study,
      we aimed to investigate the association between these specific ABCB1
      polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a
      history of CAA and 91 control patients without a history of CAA, despite 10 years
      of continuous clozapine use, were included. Patient recruitment and blood sample
      collection were conducted at the Hacettepe University Faculty of Medicine,
      Department of Psychiatry, in collaboration with the members of the Schizophrenia
      and Other Psychotic Disorders Section of the Psychiatric Association of Turkey,
      working in various psychiatry clinics. After DNA extraction from peripheral blood
      lymphocytes, genotyping was performed using polymerase chain reaction and
      endonuclease digestion. Patients with CAA had shorter duration of clozapine use
      but did not show any significant difference in other clinical, sociodemographic
      characteristics and in genotypic or allelic distributions of ABCB1 variants and
      haplotypes compared with control patients. Among the 10 patients with CAA, none
      carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this
      haplotype was approximately 12% among the controls. Larger sample size studies
      and thorough genetic analyses may reveal both genetic risk and protective factors
      for this serious adverse event. 

PMID- 27043127
TI  - Anthocyanins in obesity-associated thrombogenesis: a review of the potential
      mechanism of action.
AB  - Platelet dysfunction, oxidative stress and dyslipidemia are important
      contributors to pro-thrombotic progression particularly in obese and hyper
      cholesterolemic populations. Becoming an increasingly widespread endemic, obesity
      causes a dysfunction in the metabolic system by initiating endothelial
      dysfunction; increasing free radical production; lipid peroxidation; platelet
      hyperactivity and aggregation; thereby accelerating thrombogenesis. In the event
      of increased free radical generation under pro-thrombotic conditions,
      antioxidants act as scavengers in reducing physiological oxidative stress; free
      radical-mediated thrombosis and hemostatic function. Anthocyanin, a subclass of
      the polyphenol family flavonoids has been shown to exhibit anti-dyslipidemic and
      anti-thrombotic properties by virtue of its antioxidant activity. Current anti
      platelet/coagulant therapeutics target specific receptor pathways to relieve the
      extent of dysfunction and plaque acceleration in pro-thrombotic individuals.
      Though effective, they have been associated with high bleeding risk and increased
      response variability. The following review focuses on the potential role of
      natural dietary anthocyanins in targeting simultaneous mechanistic pathways in
      alleviating platelet activation, dyslipidemia, and oxidative stress-associated
      thrombus acceleration in obese pro-thrombotic populations. 

PMID- 27043128
TI  - Macro- and Micronutrient Simultaneous Slow Release from Highly Swellable
      Nanocomposite Hydrogels.
AB  - Clay-loaded hydrogels have been arousing great interest from researchers and
      academics due to their unique properties and broad applicability range. Here we
      developed hydrogel-based nanocomposites intended for slow/controlled release of
      macro- and micronutrients into independent or concurrent systems. The produced
      nanocomposites underwent a hydrolysis treatment that improved their
      physicochemical properties. We obtained materials capable of absorbing water
      contents 5000 times greater than their weights, an outcome that makes them
      promising, particularly if compared with commercially available materials. Though
      swelling degree was affected by the presence of calcium montmorillonite (MMt),
      MMt has increased nutrient (urea and boron) loading capacity and, as a
      consequence of its interaction with the studied nutrients, has led to a slower
      release behavior. By evaluating the simultaneous release behavior, we observed
      that both the ionic (sodium octaborate) and the nonionic (urea) sources competed
      for the same active sites within the nanocomposites as suggested by the decreased
      loading and release values of both nutrients when administrated simultaneously.
      Because of its great swelling degree, higher than 2000 times in water, the
      nanocomposites formulated with high MMt contents (approximately 50.0% wt) as well
      as featuring high loading capacity and individual (approximately 74.2 g of urea
      g(-1) of nanocomposite and 7.29 g of boron g(-1) of nanocomposite) and
      simultaneous release denote interesting materials for agricultural applications
      (e.g., carriers for nutrient release). 

PMID- 27043129
TI  - Fulminant Central Nervous System Nocardiosis in a Patient Treated With
      Alemtuzumab for Relapsing-Remitting Multiple Sclerosis.

PMID- 27043130
TI  - Asymmetric Total Syntheses of ent-Ascospiroketals A and B.
AB  - A new hypothetic biosynthesis of the tricyclic spiroketal core of ascospiroketals
      A and B is proposed, which guided the development of a novel synthetic strategy
      for the asymmetric total synthesis of ent-ascospiroketals A and B. The synthesis
      features an efficient ring contraction rearrangement of the 10-membered lactone
      to the tricyclic spiroketal cis-fused gamma-lactone core, which served as the
      common intermediate for the synthesis of both ent-ascospiroketals A and B through
      the Stille coupling reaction at the final step. In addition, seven diastereomers
      were prepared to conclusively confirm the structure of ent-ascospiroketal B. 

PMID- 27043131
TI  - Solubilization of Hexafluorobenzene by the Micellar Aromatic Core Formed from
      Aggregation of Amphiphilic (2,3-O-Dibenzyl-6-O-sulfobutyl) Cyclodextrins.
AB  - Aggregation colloids that possess an aromatic pseudophase in an aqueous system
      could provide new avenues of research including micellar catalysis, aqueous
      remediation, and emulsion polymerization studies. The apparent aggregation of two
      macrocyclic surfactants, hexakis (2,3-O-dibenzyl-6-O-sulfobutyl)
      cyclomaltohexaose (DBSBA) and heptakis (2,3-O-dibenzyl-6-O-sulfobutyl)
      cyclomaltoheptaose (DBSBB), was investigated using diffusion ordered nuclear
      magnetic resonance (NMR) spectroscopy (DOSY), conductivity, and pyrene
      fluorescence techniques. These amphiphiles were found to possess near spherical
      symmetry at critical micelle concentrations of approximately 0.1 mM in all
      techniques used to study the phenomenon. Aggregation of both surfactants was
      found to be entropically driven at low temperatures but enthalpically driven at
      higher temperatures. The calculated compensation temperatures of DBSBA and DBSBB
      were determined to be 317 and 307 K, respectively. These surfactants contain a
      high percentage of aromatic moieties in their structures, which affects the
      thermodynamics of aggregation and their interior micellar environment. The
      proposed aromatic micellar core was tested using hexafluorobenzene (HFB) as a
      molecular probe in (19)F NMR experiments. (19)F NMR relaxation and chemical shift
      studies found the HFB quantitatively partitioned into the micellar interiors.
      Global regression analysis found that HFB interaction with DBSBA micelles
      possessed at least two association constants, differing by an order of magnitude,
      the largest being in excess of 8300 M(-1). DBSBB micellar interactions with HFB
      were found to be weaker, although in excess of 1100 M(-1), with a subsequent
      association constant of similar magnitude. Benzyl substituents of DBSBB are
      required for solubilization of HFB. Heteronuclear Overhauser effect spectroscopy
      (HOESY, (19)F-(1)H) of the DBSBB:HFB complex revealed strong interaction of HFB
      with benzyl substituents but not the cyclodextrin cavity.

PMID- 27043132
TI  - Fully Understanding the Photochemical Properties of Bi2O2(CO3)1-xSx Nanosheets.
AB  - The photochemical properties of crystal facets with obviously distinct atomic and
      geometric structures have been studied widely to date. However, little work has
      been performed for two or more facets with very similar atomic and geometric
      structures. Herein, we mainly report the photochemical properties of {001} and
      {100} facets of Bi2O2(CO3)1-xSx with very similar atomic and geometric
      structures. The simulation and experimental results show that over {100} facets,
      sulfur prefers to substitute for the carbonate anion, leading to the formation of
      an interesting serpentine internal electric field that greatly inhibits the
      charge recombining of electrons and holes, which has rarely been demonstrated;
      over {001} facets, however, sulfur preferentially adsorbs in oxygen vacancies,
      which greatly reduces the surface energy of {001} facets, leading to 80% of the
      high-energy {001} facets exposed. As a result, the photochemical properties of
      nanosheets have been greatly improved. This study could help us to fully
      understand the photochemical properties of semiconductors.

PMID- 27043133
TI  - A Prospective Virtual Screening Study: Enriching Hit Rates and Designing Focus
      Libraries To Find Inhibitors of PI3Kdelta and PI3Kgamma.
AB  - Here, we report a high-throughput virtual screening (HTVS) study using
      phosphoinositide 3-kinase (both PI3Kgamma and PI3Kdelta). Our initial HTVS
      results of the Janssen corporate database identified small focused libraries with
      hit rates at 50% inhibition showing a 50-fold increase over those from a HTS
      (high-throughput screen). Further, applying constraints based on "chemically
      intuitive" hydrogen bonds and/or positional requirements resulted in a
      substantial improvement in the hit rates (versus no constraints) and reduced
      docking time. While we find that docking scoring functions are not capable of
      providing a reliable relative ranking of a set of compounds, a prioritization of
      groups of compounds (e.g., low, medium, and high) does emerge, which allows for
      the chemistry efforts to be quickly focused on the most viable candidates. Thus,
      this illustrates that it is not always necessary to have a high correlation
      between a computational score and the experimental data to impact the drug
      discovery process.

PMID- 27043134
TI  - Cross-Culture Validation of the HIV/AIDS Stress Scale: The Development of a
      Revised Chinese Version.
AB  - BACKGROUND: Being HIV-infected is a stressful experience for many individuals. To
      assess HIV-related stress in the Chinese context, a measure with satisfied
      psychometric properties is yet underdeveloped. This study aimed to examine the
      psychometric characteristics of a simplified Chinese version of the HIV/AIDS
      Stress Scale (SS-HIV) among people living with HIV/AIDS in central China. METHOD:
      A total of 667 people living with HIV (92% were male) were recruited from March
      1st 2014 to August 31th 2015 by consecutive sampling. A standard questionnaire
      package containing the Chinese HIV/AIDS Stress Scale (CSS-HIV), the Chinese
      Patient Health Questionnaire-9 (PHQ-9), and the Chinese Generalized Anxiety
      Disorder Scale (GAD-7) were administered to all participants, and 38 of the
      participants were selected randomly to be re-tested in four weeks after the
      initial testing. RESULTS: Our data supported that a revised 17-item CSS-HIV had
      adequate psychometric properties. It consisted of 3 factors: emotional stress (6
      items), social stress (6 items) and instrumental stress (5 items). The overall
      Cronbach's alpha was 0.906, and the test-retest reliability coefficient was
      0.832. The revised CSS-HIV was significantly correlated with the number of HIV
      related symptoms, as well as scores on the PHQ-9 and GAD-7, indicating acceptable
      concurrent validity. CONCLUSION: The 17-item Chinese version of the SS-HIV has
      potential research and clinical utility in identifying important stressors among
      the Chinese HIV-infected population and in understanding the effects of stress on
      adjustment to HIV.

PMID- 27043136
TI  - Simulating the Effects of Sea Level Rise on the Resilience and Migration of Tidal
      Wetlands along the Hudson River.
AB  - Sea Level Rise (SLR) caused by climate change is impacting coastal wetlands
      around the globe. Due to their distinctive biophysical characteristics and unique
      plant communities, freshwater tidal wetlands are expected to exhibit a different
      response to SLR as compared with the better studied salt marshes. In this study
      we employed the Sea Level Affecting Marshes Model (SLAMM), which simulates
      regional- or local-scale changes in tidal wetland habitats in response to SLR,
      and adapted it for application in a freshwater-dominated tidal river system, the
      Hudson River Estuary. Using regionally-specific estimated ranges of SLR and
      accretion rates, we produced simulations for a spectrum of possible future
      wetland distributions and quantified the projected wetland resilience, migration
      or loss in the HRE through the end of the 21st century. Projections of total
      wetland extent and migration were more strongly determined by the rate of SLR
      than the rate of accretion. Surprisingly, an increase in net tidal wetland area
      was projected under all scenarios, with newly-formed tidal wetlands expected to
      comprise at least 33% of the HRE's wetland area by year 2100. Model simulations
      with high rates of SLR and/or low rates of accretion resulted in broad shifts in
      wetland composition with widespread conversion of high marsh habitat to low
      marsh, tidal flat or permanent inundation. Wetland expansion and resilience were
      not equally distributed through the estuary, with just three of 48 primary
      wetland areas encompassing >50% of projected new wetland by the year 2100. Our
      results open an avenue for improving predictive models of the response of
      freshwater tidal wetlands to sea level rise, and broadly inform the planning of
      conservation measures of this critical resource in the Hudson River Estuary. 

PMID- 27043135
TI  - The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine
      Concentration and Selected Biochemical Parameters in Wistar Rats.
AB  - Iodine is one of the trace elements which are essential for mammalian life. The
      major objective of iodine biofortification of plants is to obtain food rich in
      this trace element, which may increase its consumption by various populations.
      Additionally, it may reduce the risk of iodine deficiency diseases. In this
      research for the first time we have assessed the bioavailability of iodine from
      raw or cooked carrot biofortified with this trace element on iodine concentration
      in selected tissues and various biochemical parameters as well as mRNA expression
      of some genes involved in iodine metabolism in Wistar rats. Statistically, a
      significantly higher iodine level was determined in urine, faeces and selected
      tissues of rats fed a diet containing biofortified raw carrot as compared to a
      diet without iodine and a diet containing control cooked carrot. Biofortified raw
      carrot significantly increased triiodothyronine concentration as compared to
      animals from other experimental groups. The highest thyroid stimulating hormone
      level was determined in rats fed control cooked carrots. mRNA expression of
      selected genes was affected by different dietary treatment in rats' hearts.
      Biofortified raw and cooked carrot could be taken into account as a potential
      source of iodine in daily diets to prevent iodine deficiency in various
      populations. 

PMID- 27043137
TI  - Stereodivergent and Protecting-Group-Free Synthesis of the Helicascolide Family:
      A Rhodium-Catalyzed Atom-Economical Lactonization Strategy.
AB  - Natural products of polyketide origin, in particular small-sized lactones often
      possess a very broad range of impressive biological activities. An efficient way
      to demonstrate the concise access to six-membered lactones was emphasized as part
      of a stereodivergent and protecting-group-free synthesis of all three
      representatives of the helicascolide family. This strategy features an atom
      economical and highly diastereoselective rhodium-catalyzed "head-to-tail"
      lactonization by an intramolecular addition of omega-allenyl-substituted
      carboxylic acids to terminal allenes, including the selective construction of a
      new stereocenter in the newly formed core structures. The excellent selectivities
      with which the helicascolide precursors were obtained are remarkable, thus
      resulting in an expeditious and highly efficient natural product synthesis.

PMID- 27043138
TI  - A SURVEY OF NONXANTHINE DERIVATIVES AS ADENOSINE RECEPTOR LIGANDS.
AB  - The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range
      of heterocyclic derivatives have been determined. Mono-, bi-, tricyclic and
      macrocyclic compounds were screened in binding assays, using either [3H]PIA or
      [3H]CGS 21680 in rat brain membranes or [125I]AB-MECA in CHO cells stably
      transfected with rat A3 receptors. Several new classes of adenosine antagonists
      (e.g. 5-oxoimidazopyrimidines and a pyrazoloquinazoline) were identified. Various
      sulfonylpiperazines, 11-hydroxytetrahydrocarbazolenine, 4H-pyrido[1,2
      a]pyrimidinone, folic acid, and cytochalasin H and J bound to A3 receptors
      selectively. Moreover, cytochalasin A, which bound to A1 adenosine receptors with
      Ki value of 1.9 MUM, inhibited adenylyl cyclase in rat adipocytes, but not via
      reversible A1 receptor binding.

PMID- 27043139
TI  - Fall-Related Psychological Concerns and Anxiety among Community-Dwelling Older
      Adults: Systematic Review and Meta-Analysis.
AB  - Fear of falling and other fall-related psychological concerns (FRPCs), such as
      falls-efficacy and balance confidence, are highly prevalent among community
      dwelling older adults. Anxiety and FRPCs have frequently, but inconsistently,
      been found to be associated in the literature. The purpose of this study is to
      clarify those inconsistencies with a systematic review and meta-analysis and to
      evaluate if the strength of this relationship varies based on the different FRPC
      constructs used (e.g., fear of falling, falls-efficacy or balance confidence). A
      systematic review was conducted through multiple databases (e.g., MEDLINE,
      PsycINFO) to include all articles published before June 10th 2015 that measured
      anxiety and FRPCs in community-dwelling older adults. Active researchers in the
      field were also contacted in an effort to include unpublished studies. The
      systematic review led to the inclusion of twenty relevant articles (n = 4738). A
      random-effect meta-analysis revealed that the mean effect size for fear of
      falling and anxiety is r = 0.32 (95% CI: 0.22-0.40), Z = 6.49, p < 0.001 and the
      mean effect size for falls-efficacy or balance confidence and anxiety is r = 0.31
      (95% CI: 0.23-0.40), Z = 6.72, p < 0.001. A Q-test for heterogeneity revealed
      that the two effect sizes are not significantly different (Q(19) = 0.13, p =
      n.s.). This study is the first meta-analysis on the relationship between anxiety
      and FRPCs among community-dwelling older adults. It demonstrates the importance
      of considering anxiety when treating older adults with FRPCs. 

PMID- 27043140
TI  - Raman Barcode for Counterfeit Drug Product Detection.
AB  - Potential infiltration of counterfeit drug products-containing the wrong or no
      active pharmaceutical ingredient (API)-into the bona fide drug supply poses a
      significant threat to consumers worldwide. Raman spectroscopy offers a rapid,
      nondestructive avenue to screen a high throughput of samples. Traditional
      qualitative Raman identification is typically done with spectral correlation
      methods that compare the spectrum of a reference sample to an unknown. This is
      often effective for pure materials but is quite challenging when dealing with
      drug products that contain different formulations of active and inactive
      ingredients. Typically, reliable identification of drug products using common
      spectral correlation algorithms can only be made if the specific product under
      study is present in the library of reference spectra, thereby limiting the scope
      of products that can be screened. In this paper, we introduce the concept of the
      Raman barcode for identification of drug products by comparing the known peaks in
      the API reference spectrum to the peaks present in the finished drug product
      under study. This method requires the transformation of the Raman spectra of both
      API and finished drug products into a barcode representation by assigning zero
      intensity to every spectral frequency except the frequencies that correspond to
      Raman peaks. By comparing the percentage of nonzero overlap between the expected
      API barcode and finished drug product barcode, the identity of API present can be
      confirmed. In this study, 18 approved finished drug products and nine simulated
      counterfeits were successfully identified with 100% accuracy utilizing this
      method.

PMID- 27043141
TI  - Dual N-Back Working Memory Training in Healthy Adults: A Randomized Comparison to
      Processing Speed Training.
AB  - Enhancing cognitive ability is an attractive concept, particularly for middle
      aged adults interested in maintaining cognitive functioning and preventing age
      related declines. Computerized working memory training has been investigated as a
      safe method of cognitive enhancement in younger and older adults, although few
      studies have considered the potential impact of working memory training on middle
      aged adults. This study investigated dual n-back working memory training in
      healthy adults aged 30-60. Fifty-seven adults completed measures of working
      memory, processing speed, and fluid intelligence before and after a 5-week web
      based dual n-back or active control (processing speed) training program. RESULTS:
      Repeated measures multivariate analysis of variance failed to identify
      improvements across the three cognitive composites, working memory, processing
      speed, and fluid intelligence, after training. Follow-up Bayesian analyses
      supported null findings for training effects for each individual composite.
      Findings suggest that dual n-back working memory training may not benefit working
      memory or fluid intelligence in healthy adults. Further investigation is
      necessary to clarify if other forms of working memory training may be beneficial,
      and what factors impact training-related benefits, should they occur, in this
      population.

PMID- 27043142
TI  - Master's Perspective: Joseph Bloomer, M.D.

PMID- 27043144
TI  - Risk factors and predictors of uncontrolled hyperglycemia and diabetic
      ketoacidosis in children and adolescents with type 1 diabetes mellitus in Jeddah,
      western Saudi Arabia.
AB  - BACKGROUND: Little is known about levels of glycemic control and risk factors for
      uncontrolled hyperglycemia in Saudi children with type 1 diabetes mellitus
      (T1DM). The aim of the present study was to identify levels of glycemic control,
      risk factors and predictors of uncontrolled hyperglycemia (HG) and diabetic
      ketoacidosis (DKA) in children with T1DM. METHODS: A retrospective study was
      performed on Saudi children and adolescents with confirmed T1DM who were followed
      at the Pediatric Endocrinology Clinic of the Maternity and Children Hospital,
      Jeddah, from 2000 to 2014. Data collection included all possible factors that may
      be associated with uncontrolled T1DM. Patients were classified according to
      American Diabetes Association guidelines for target HbA1c levels per age group.
      Comparisons were made between well-controlled (WC) patients, HG patients, and DKA
      patients. Calculation of odds ratios and logistic regression allowed for
      estimation of the role of each risk factor in uncontrolled T1DM. RESULTS: Only
      31.2 % of children and adolescents with T1DM were well controlled. Better
      glycemic control was associated with age < 6 years, urban residence, and T1DM
      duration <5 years. Glycemic control was not affected by gender, insulin therapy,
      or comorbidities. The most significant independent predictors of hyperglycemia
      and DKA were poor compliance with a healthy lifestyle (adjusted hazards ratio
      [AHR] 28.94; 95 % confidence interval [CI] 8.37-100.04) and an excess intake of
      sweets (AHR 3.31; 95 % CI 1.54-7.11). CONCLUSION: The most significant
      independent predictor for poor glycemic control (particularly DKA rather than
      hyperglycemia) in Saudi children and adolescents was poor compliance with a
      healthy lifestyle with an excessive intake of sweets.

PMID- 27043143
TI  - Increased Reactive Oxygen Species Formation and Oxidative Stress in Rheumatoid
      Arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder.
      Highly reactive oxygen free radicals are believed to be involved in the
      pathogenesis of the disease. In this study, RA patients were sub-grouped
      depending upon the presence or absence of rheumatoid factor, disease activity
      score and disease duration. RA Patients (120) and healthy controls (53) were
      evaluated for the oxidant-antioxidant status by monitoring ROS production,
      biomarkers of lipid peroxidation, protein oxidation and DNA damage. The level of
      various enzymatic and non-enzymatic antioxidants was also monitored. Correlation
      analysis was also performed for analysing the association between ROS and various
      other parameters. METHODS: Intracellular ROS formation, lipid peroxidation (MDA
      level), protein oxidation (carbonyl level and thiol level) and DNA damage were
      detected in the blood of RA patients. Antioxidant status was evaluated by FRAP
      assay, DPPH reduction assay and enzymatic (SOD, catalase, GST, GR) and non
      enzymatic (vitamin C and GSH) antioxidants. RESULTS: RA patients showed a higher
      ROS production, increased lipid peroxidation, protein oxidation and DNA damage. A
      significant decline in the ferric reducing ability, DPPH radical quenching
      ability and the levels of antioxidants has also been observed. Significant
      correlation has been found between ROS and various other parameters studied.
      CONCLUSION: RA patients showed a marked increase in ROS formation, lipid
      peroxidation, protein oxidation, DNA damage and decrease in the activity of
      antioxidant defence system leading to oxidative stress which may contribute to
      tissue damage and hence to the chronicity of the disease.

PMID- 27043145
TI  - Tobacco and alcohol consumption after total laryngectomy and survival: A German
      multicenter prospective cohort study.
AB  - BACKGROUND: We examined the relation of tobacco and alcohol consumption after
      total laryngectomy with overall survival (OS). METHODS: Tobacco and alcohol
      consumption was assessed at 5 time points after total laryngectomy. Patients were
      followed up for survival until December 31, 2014. A multivariate Cox regression
      was fitted to test for differences in OS. RESULTS: Three hundred fifty-nine
      patients were included in this study. Compared to former smokers, never smokers
      had hazard ratios (HRs) of 0.88 (95% confidence intervals [CIs] = 0.50-1.59), and
      continuous smokers 1.31 (95% CI = 0.87-1.96). Constantly high alcohol consumption
      after total laryngectomy had an HR of 2.19 (95% CI = 1.30-3.67). Duration of
      smoking (HR = 1.00; 95% CI = 0.99-1.01) and last known status of alcohol
      consumption (HR = 1.00; 95% CI = 0.76-1.33) was not related to OS. CONCLUSION:
      Patients who smoke after total laryngectomy have a 30% higher risk of dying than
      people who gave up smoking, and constant high alcohol consumption is also a
      strong risk factor for dying. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1324
      1329, 2016.

PMID- 27043146
TI  - Perceptions and practices of physicians regarding outpatient parenteral
      antibiotic therapy in persons who inject drugs.

PMID- 27043147
TI  - Spatio-temporal variations in photosynthesis.

PMID- 27043148
TI  - Isolation of a new cytotoxic polyhydroxysterol from the South China Sea soft
      coral Sinularia sp.
AB  - A new polyhydroxysterol, (22E)-24-methylenecholestane-22-ene-3beta,5alpha,6beta
      triol (1), together with four known analogues (2-5) were isolated from the South
      China Sea soft coral Sinularia sp. Their structures were elucidated by
      spectroscopic analyses and comparison with previously reported data. All these
      compounds exhibited cytotoxic effect against both HepG2 and HeLa cell lines with
      IC50 values ranging from 8.36 to 37.30 MUM. Preliminary structure-activity
      relationship study identified that the presence of double bonds in the side
      chains of these polyhydroxysterols significantly reduced the biological effect
      obtained.

PMID- 27043149
TI  - Mass spectrometric quantification of urinary human liver fatty acid binding
      protein in renal transplant recipients.
AB  - RATIONALE: Urinary liver fatty acid binding protein (L-FABP) has been evaluated
      as a promising early biomarker of renal ischemia in human kidney transplant
      patients. The use of L-FABP in clinical practice requires that this biomarker be
      associated with an analytical method that combines specificity, accuracy and
      robustness. This study aimed to evaluate an optimized multiple reaction
      monitoring (MRM) method using ultrafast liquid chromatography coupled with tandem
      mass spectrometry to measure urinary L-FABP levels in renal transplant
      recipients. METHODS: Purified recombinant human L-FABP tryptic standard was
      analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry (MS/MS) and liquid chromatography (LC)/MS/MS to select for
      peptides that provided specificity and adequate response in developing an MRM
      method for urinary L-FABP quantification. Human urine samples collected from
      kidney transplant recipients were isolated, concentrated, precipitated and
      trypsin digested before mass spectrometric analysis of L-FABP. L-FABP levels were
      also measured in urine samples by enzyme immunoassay. RESULTS: The tryptic
      peptide ion MH(+) of (50) FTITAGSK(57) (m/z 824) provided an adequate signal and
      was used for quantification of L-FABP under conditions employed for LC/MS/MS
      analysis. MALDI-TOF-MS/MS spectra obtained by collision-induced dissociation of
      the parent MH(+) ion (50) FTITAGSK(57) resulted in a y3 product ion that was used
      for quantitative analysis by the MRM method. Urinary L-FABP content measured by
      both ELISA and LC/MS/MS after transplantation was significantly higher compared
      to before transplantation levels. The Spearman correlation coefficient between
      the two methods was statistically significant. Intra-day and inter-day
      coefficients of variation provided good repeatability and reproducibility for
      validation of LC/MS/MS analysis. CONCLUSIONS: LC/MS/MS quantification of L-FABP
      may provide a new reference method to determine changes in this potential
      biomarker in human kidney transplant patients.

PMID- 27043150
TI  - Identification of new KLF1 and LU alleles during the resolution of Lutheran
      typing discrepancies.
AB  - BACKGROUND: The Lu(b) antigen is expressed on red blood cells (RBCs) of the
      majority of individuals in all populations. Its absence in transfused patients
      may lead to alloantibody production and mild-to-moderate transfusion reactions,
      and in pregnancies to mild hemolytic disease of the fetus and newborn. This
      report describes the results of discrepancy resolution between apparent LU*A/LU*B
      or LU*B/LU*B genotypes and apparent Lu(b-) or Lu(b+ weak) phenotypes in one Asian
      and 10 Caucasian blood donors. STUDY DESIGN AND METHODS: Whole blood samples were
      analyzed by molecular methods to resolve discrepancies between Lu(b-) phenotypes
      detected by serology and Lu(b+) phenotypes predicted by genotyping. RBC
      agglutination assays were performed with commercial and patient antisera by tube
      or gel column methods. Genotyping was performed on commercial arrays that target
      the LU*A/LU*B polymorphism at Position c.230. The discrepancies were resolved by
      sequencing of genomic DNA and in some cases by sequencing of cloned DNA
      fragments. RESULTS: Eleven new alleles with coding sequence variants were
      identified, seven in the KLF1 gene, which are presumed to act dominantly to
      silence LU expression, and four in the LU gene itself. The alleles are
      KLF1*114delC, KLF1*298T, KLF1*304C,484insC, KLF1*304C,1000del2, KLF1*621G,
      KLF1*948delC, KLF1*1040A,1045delT, LU*B(559T,711T,714T), LU*B(611A,638T),
      LU*B(1049del2ins3), and LU*B(1306T,1340T,1671T,1742T). CONCLUSION: Besides
      confirming common phenotypes and detecting rare antigen-negative phenotypes, the
      use of molecular methods in blood donor typing can prompt the identification of
      new alleles through discrepancy resolution.

PMID- 27043151
TI  - Is there a role for salvage lymphadenectomy as second-line therapy post-robotic
      radical prostatectomy?

PMID- 27043152
TI  - Stochastic Network Models in Neuroscience: A Festschrift for Jack Cowan.
      Introduction to the Special Issue.
AB  - Jack Cowan's remarkable career has spanned, and molded, the development of
      neuroscience as a quantitative and mathematical discipline combining deep
      theoretical contributions, rigorous mathematical work and groundbreaking
      biological insights. The Banff International Research Station hosted a workshop
      in his honor, on Stochastic Network Models of Neocortex, July 17-24, 2014. This
      accompanying Festschrift celebrates Cowan's contributions by assembling current
      research in stochastic phenomena in neural networks. It combines historical
      perspectives with new results including applications to epilepsy, path-integral
      methods, stochastic synchronization, higher-order correlation analysis, and
      pattern formation in visual cortex. 

PMID- 27043153
TI  - Adrenal responses to a low-dose short synacthen test in children with asthma.

PMID- 27043155
TI  - Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment
      response in rheumatoid arthritis.
AB  - Important advances have occurred during the last decade in the understanding of
      the pathogenesis of rheumatoid arthritis (RA). However, we are still far from
      having a clear picture of the molecular network that predisposes an individual to
      develop the disease, to worsen the symptoms after that, or to successfully
      respond to a specific treatment. In this sense, different -omics fields
      (including transcriptomics, proteomics, metabolomics, genomics and epigenomics)
      have recently produced promising insights that could definitively help us to
      sharpen such picture if integrated trough a systems biology approach. In this
      review we will summarise and discuss the recent progress achieved in those fields
      and its possible impact on the discovery of suitable biomarkers for RA diagnosis,
      prognosis and treatment response.

PMID- 27043154
TI  - Bone morphogenetic protein signaling in musculoskeletal cancer.
AB  - PURPOSE: Bone morphogenetic proteins (BMPs) belong to the transforming growth
      factor-beta (TGF-beta) superfamily of proteins; they were initially named after
      their ability to induce ectopic bone formation. Published studies have proved
      BMPs' role in a variety of biological processes such as embryogenesis and
      patterning of body axes, and maintaining adult tissue homeostasis. Other studies
      have focused on BMPs properties, functions and possible involvement in skeletal
      diseases, including cancer. METHODS: A literature search mainly paying attention
      to the role of BMPs in musculoskeletal tumors was performed in electronic
      databases. RESULTS: This article discusses BMPs synthesis and signaling, and
      summarizes their prominent roles in the skeletal system for the differentiation
      of osteoblasts, osteocytes and chondrocytes. CONCLUSIONS: The review emphasizes
      on the role of BMP signaling in the initiation and progression of musculoskeletal
      cancer.

PMID- 27043156
TI  - Reproducibility of myocardial T1 and T2 relaxation time measurement using slice
      interleaved T1 and T2 mapping sequences.
AB  - PURPOSE: To assess measurement reproducibility and image quality of myocardial T1
      and T2 maps using free-breathing slice-interleaved T1 and T2 mapping sequences at
      1.5 Tesla (T). MATERIALS AND METHODS: Eleven healthy subjects (33 +/- 16 years; 6
      males) underwent a slice-interleaved T1 and T2 mapping test/retest cardiac MR
      study at 1.5T on 2 days. For each day, subjects were imaged in two sessions with
      removal out of the magnet and repositioning before the subsequent session. We
      studied measurement reproducibility as well as the required sample size for
      sufficient statistical power to detect a predefined change in T1 and T2 . In a
      separate prospective study, we assessed T1 and T2 map image quality in 241
      patients (54 +/- 15 years; 73 women) with known/suspected cardiovascular disease
      referred for clinical cardiac MR. A subjective quality score was used to assess a
      segment-based image quality. RESULTS: In the healthy cohort, the slice
      interleaved T1 measurements were highly reproducible, with global coefficients of
      variation (CVs) of 2.4% between subjects, 2.1% between days, and 1.7% between
      sessions. Slice-interleaved T2 mapping sequences provided similar reproducibility
      with global CVs of 7.2% between subjects, 6.3% between days, and 5.0 between
      sessions. A lower variability resulted in a reduction of the required number of
      subjects to achieve a certain statistical power when compared with other T1
      mapping sequences. In the subjective image quality assessment, >80% of myocardial
      segments had interpretable data. CONCLUSION: Slice-interleaved T1 and T2 mapping
      sequences yield highly reproducible T1 and T2 measurements with >80% of
      interpretable myocardial segments. J. Magn. Reson. Imaging 2016;44:1159-1167.

PMID- 27043157
TI  - A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a
      Genetic Predictor of Differential Response to Psychological Treatments for Child
      Anxiety Disorders.
AB  - BACKGROUND: The differential susceptibly hypothesis suggests that certain genetic
      variants moderate the effects of both negative and positive environments on
      mental health and may therefore be important predictors of response to
      psychological treatments. Nevertheless, the identification of such variants has
      so far been limited to preselected candidate genes. In this study we extended the
      differential susceptibility hypothesis from a candidate gene to a genome-wide
      approach to test whether a polygenic score of environmental sensitivity predicted
      response to cognitive behavioural therapy (CBT) in children with anxiety
      disorders. METHODS: We identified variants associated with environmental
      sensitivity using a novel method in which within-pair variability in emotional
      problems in 1,026 monozygotic twin pairs was examined as a function of the pairs'
      genotype. We created a polygenic score of environmental sensitivity based on the
      whole-genome findings and tested the score as a moderator of parenting on
      emotional problems in 1,406 children and response to individual, group and brief
      parent-led CBT in 973 children with anxiety disorders. RESULTS: The polygenic
      score significantly moderated the effects of parenting on emotional problems and
      the effects of treatment. Individuals with a high score responded significantly
      better to individual CBT than group CBT or brief parent-led CBT (remission rates:
      70.9, 55.5 and 41.6%, respectively). CONCLUSIONS: Pending successful replication,
      our results should be considered exploratory. Nevertheless, if replicated, they
      suggest that individuals with the greatest environmental sensitivity may be more
      likely to develop emotional problems in adverse environments but also benefit
      more from the most intensive types of treatment.

PMID- 27043158
TI  - Association between serum adalimumab concentrations and endoscopic disease
      activity in patients with Crohn's disease.
AB  - BACKGROUND AND AIMS: The serum trough level of adalimumab (ADA) associated with
      mucosal healing (MH) remains unclear. Our objective was to determine the
      association between ADA trough levels and the endoscopic activity in Crohn's
      disease. MATERIALS AND METHODS: This was a cross-sectional study including 42
      patients with Crohn's disease. Endoscopic activity was assessed using the
      modified Rutgeerts scoring system. The primary outcome was mucosal healing, and
      the secondary outcomes were serum levels of C-reactive protein and albumin.
      RESULTS: Endoscopic disease activity negatively correlated with serum ADA trough
      levels (Spearman's rank correlation coefficient (rho) = -0.42, P < 0.01). MH was
      achieved in 14 of 42 patients (33.3%). Serum ADA trough levels were significantly
      higher in the MH group than in the no-MH group (ADA mean trough level, 11.7 vs
      7.5 ug/mL). The proportion of patients with ADA as the first biologic was
      significantly higher in the MH group than in the no-MH group (85.7% vs 53.5%, P =
      0.04). The ADA trough levels that were best associated with normal C-reactive
      protein and albumin levels were 5.57 ug/mL (odds ratio [OR] 16.0, specificity
      0.80) and 6.95 ug/mL (OR 9.2, specificity 0.81), respectively. The ADA trough
      level that was best associated with MH was 7.9 ug/mL (OR 13.5, specificity 0.86).
      The endoscopic disease activity was significantly higher in the patients with ADA
      as the second biologic as compared with those with ADA as the first biologic (P <
      0.05). CONCLUSION: Mucosal healing requires higher ADA trough levels, compared
      with those required to normalization of routine clinical markers.

PMID- 27043160
TI  - Regulation of IL-17A expression in mice following subacute ozone exposure.
AB  - Exposure to subacute ozone (O3) causes pulmonary neutrophil recruitment. In mice,
      this recruitment requires IL-17A. Ozone also causes expression of IL-23 and IL-1,
      which can induce IL-17A. The purpose of this study was to examine the hypothesis
      that IL-23 and IL-1 contribute to IL-17A expression and subsequent neutrophil
      recruitment after subacute O3 exposure. Wild-type, IL-23(-/-), and Flt3l(-/-)
      mice were exposed to air or 0.3 ppm O3 for 72 h. Flt3l(-/-) mice lack
      conventional dendritic cells (cDC) that can express IL-23 and IL-1. Other wild
      type mice were pre-treated with saline or the IL-1R1 antagonist anakinra prior to
      O3 exposure. After exposure, bronchoalveolar lavage (BAL) was performed and lung
      tissue harvested. The results indicated that pulmonary Il17a mRNA abundance and
      IL-17A(+) F4/80(+) cells were significantly reduced in O3-exposed IL-23(-/-) vs
      in wild-type mice. In contrast, anakinra had no effect on Il23a or Il17a
      pulmonary mRNA abundance or on BAL concentrations of the neutrophil survival
      factor G-CSF, but anakinra did reduce BAL neutrophil numbers, likely because
      anakinra also reduced BAL IL-6. Compared to air, O3 caused a significant increase
      in DC numbers in wild-type, but not in Flt3(-/-) mice. However, there was no
      significant difference in Il23a or Il17a mRNA abundance or in BAL neutrophil
      count in O3-exposed Flt3(-/-) vs in wild-type mice. From these results, it was
      concluded that IL-23 but not IL-1 contributes to the IL-17A expression induced by
      subacute O3 exposure. Induction of IL-23 by O3 does not appear to require cDC.

PMID- 27043161
TI  - Understanding and Measuring LGBTQ Pathways to Health: A Scoping Review of
      Strengths-Based Health Promotion Approaches in LGBTQ Health Research.
AB  - Health research traditionally has focused on the health risks and deficits of
      lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations, obscuring the
      determinants that can promote health across the life course. Recognizing,
      appropriately measuring, and rendering visible these determinants of health is
      paramount to informing appropriate and engaging health policies, services, and
      systems for LGBTQ populations. The overarching purpose of this article is to
      provide an overview of the findings of a scoping review aimed at exploring
      strengths-based health promotion approaches to understanding and measuring LGBTQ
      health. Specifically, this scoping review examined peer-reviewed, published
      academic literature to determine (a) existing methodological frameworks for
      studying LGBTQ health from a strengths-based health promotion approach, and (b)
      suggestions for future methodological approaches for studying LGBTQ health from a
      strengths-based health promotion approach. The findings of this scoping review
      will be used to inform the development of a study aimed at assessing the health
      of and improving pathways to health services among LGBTQ populations in Nova
      Scotia, Canada.

PMID- 27043162
TI  - Postprandial plasma glucose effects of once-weekly albiglutide for the treatment
      of type 2 diabetes.
AB  - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) vary in their structure,
      duration of action, efficacy, and safety. In order to optimize glycemic control,
      it is important to target both fasting (FPG) and postprandial plasma (PPG)
      glucose. Although phase 3 trials document the effect of GLP-1 RAs on glycated
      hemoglobin, few data are available to assess their effect on PPG. Albiglutide is
      a once-weekly GLP-1 RA with a half-life of ~ 5 days. The goal of this review is
      to summarize the effects of albiglutide on PPG in four phase 2 trials and to
      describe the PPG-lowering effects of the GLP-1 RAs. At clinically relevant doses
      (30-64 mg), albiglutide consistently lowered PPG after each meal in addition to
      its effect on lowering FPG. Multiple weekly subcutaneous injections of
      albiglutide led to improvements in a variety of glycemic measures, including
      maximal reductions in PPG from baseline, postmeal glucose excursions, and FPG.
      Albiglutide, a longer-acting GLP-1 RAs, provides reductions in FPG, PPG following
      meals, and glucose over 24 hours. 

PMID- 27043163
TI  - TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis.
AB  - CONTEXT: The TSH receptor (TSHR) is considered the main target of stimulatory
      autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it
      has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also
      play a role. OBJECTIVE: We previously demonstrated that a monoclonal stimulatory
      TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital
      fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]).
      We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is
      involved in the mediation of GO pathogenesis stimulated by Graves'
      autoantibodies. DESIGN/SETTING/PARTICIPANTS: Immunoglobulins were purified from
      the sera of 57 GO patients (GO-Igs) and tested for their ability to activate TSHR
      and/or IGF-1R directly and TSHR/IGF-1R cross talk in primary cultures of GOFs.
      Cells were treated with M22 or GO-Igs with or without IGF-1R inhibitory
      antibodies or linsitinib, an IGF-1R kinase inhibitor. MAIN OUTCOME MEASURES:
      Hyaluronan (hyaluronic acid [HA]) secretion was measured as a major biological
      response for GOF stimulation. IGF-1R autophosphorylation was used as a measure of
      direct IGF-1R activation. TSHR activation was determined through cAMP production.
      RESULTS: A total of 42 out of 57 GO-Ig samples stimulated HA secretion. None of
      the GO-Ig samples exhibited evidence for IGF-1R autophosphorylation. Both anti
      IGF-1R antibodies completely inhibited IGF-1 stimulation of HA secretion. By
      contrast, only 1 IGF-1R antibody partially blocked HA secretion stimulated by M22
      or GO-Igs in a manner similar to linsitinib, whereas the other IGF-1R antibody
      had no effect on M22 or GO-Ig stimulation. These findings show that the IGF-1R is
      involved in GO-Igs stimulation of HA secretion without direct activation of IGF
      1R. CONCLUSIONS: IGF-1R activation by GO-Igs occurs via TSHR/IGF-1R cross talk
      rather than direct binding to IGF-1R, and this cross talk is important in the
      pathogenesis of GO.

PMID- 27043164
TI  - The effect of two passive head-down tilt positions on diaphragm excursion in
      healthy adults: A preliminary study.
AB  - BACKGROUND AND PURPOSE: A head-down tilt position could influence diaphragm
      excursion due to abdominal content displacement. The purpose of the study was to
      determine if excursion could be influenced by a head-down tilt position and if
      this change in excursion alters the diaphragm function. DESIGN: Prospective quasi
      experimental study. PARTICIPANTS: Seventy healthy adult students. INTERVENTION:
      Four head-down tilt positions: 1) 15 degrees  (30 seconds); 2) 15 degrees  (120
      seconds); 3) 30 degrees  (30 seconds); and 4) 30 degrees  (120 seconds). OUTCOME
      MEASURES: Change in diaphragm excursion was assessed using M-Mode ultrasound and
      diaphragm function was recorded in terms of the peak expiratory flow rate (PEFR)
      and thoracic expansion. Data were analyzed using descriptive statistics, Analysis
      of Variance (ANOVA), Kruskal Wallis and student's t-test. RESULTS: The cohort
      consisted of 56 women (80%) and 14 men (20%) with a mean age of 20.7 (+/-1.7)
      years and a mean body mass index (BMI) of 23.0 (+/-3.7) kg/m(2). The greatest
      mean change in the hemi-diaphragm, for both genders measured from rest, was 38.8
      (+/-11.5) mm on the left and 39.4 (+/-11.9) mm on the right. The greatest stretch
      occurred after a 30 degrees  head-down tilt for 30 seconds for both the right and
      left hemi-diaphragms in males and right hemi-diaphragm in females. The left hemi
      diaphragm in females achieved its maximum stretch after 30 degrees  head-down
      tilt for 120 seconds. No significant changes in thoracic expansion or PEFR were
      observed but baseline values were less than predicted. CONCLUSION: Optimal change
      in hemi-diaphragm excursion was obtained utilizing 30 degrees  head-down tilt
      positions in healthy subjects.

PMID- 27043166
TI  - Does cultural and linguistic diversity affect health-related outcomes for people
      with stroke at discharge from hospital?
AB  - PURPOSE: Primary purpose to determine if cultural and linguistic diversity
      affects health-related outcomes in people with stroke at discharge from hospital
      and secondary purpose to explore whether interpreter use alters these outcomes.
      METHOD: Systematic search of: Cochrane, PEDro, CINAHL, Medline, Pubmed, Embase,
      PsycINFO and Ageline databases. Publications were classified into whether they
      examined the impact of diversity in culture, or language or culture and language
      combined. Quality of evidence available was summarized using Best Evidence
      Synthesis. RESULTS: Eleven studies met inclusion criteria and were reviewed. Best
      Evidence Synthesis indicated conflicting evidence about the impact of culture
      alone and language barriers alone on health-related outcomes. There was strong
      evidence that hospital length of stay does not differ between groups when the
      combined impact of culture and language was investigated. Conflicting evidence
      was found for other outcomes including admission, discharge and change in FIM
      scores, and post-hospital discharge living arrangements. It is unknown if
      interpreter use alters health-related outcomes, because this was infrequently
      reported. CONCLUSION: The current limited research suggests that cultural and
      linguistic diversity does not appear to impact on health-related outcomes at
      discharge from hospital for people who have had a stroke, however further
      research is needed to address identified gaps. Implications for Rehabilitation
      The different language, culture and beliefs about health demonstrated by patients
      with stroke from minority groups in North America do not appear to significantly
      impact on their health-related outcomes during their admission to hospital. It is
      not known whether interpreter use influences outcomes in stroke rehabilitation
      because there is insufficient high quality research in this area. Clinicians in
      countries with different health systems and different cultural and linguistic
      groups within their communities need to view the results with caution as further
      investigation is required outside North America to ensure optimal and equitable
      care for these groups. In the absence of clear outcomes from high quality
      research, clinicians should ensure patients and their families have an optimal
      understanding of the health condition, the rehabilitation process and the service
      system, irrespective of language or cultural differences.

PMID- 27043167
TI  - Adsorption of elemental mercury vapors from synthetic exhaust combustion gas onto
      HGR carbon.
AB  - An activated carbon commercially available named HGR, produced by Calgon-Carbon
      Group, was used to adsorbe metallic mercury. The work is part of a wider research
      activity by the same group focused on the removal of metallic and divalent
      mercury from combustion flue gas. With respect to previously published papers,
      this one is aimed at studying in depth thermodynamic equilibria of metallic
      mercury adsorption onto a commercial activated carbon. The innovativeness lies in
      the wider operative conditions explored (temperature and mercury concentrations)
      and in the evaluation of kinetic and thermodynamic data for a commercially
      available adsorbing material. In detail, experimental runs were carried out on a
      laboratory-scale plant, in which Hg degrees  vapors were supplied in a nitrogen
      gas stream at different temperature and mercury concentration. The gas phase was
      flowed through a fixed bed of adsorbent material. Adsorbate loading curves for
      different Hg degrees  concentrations together with adsorption isotherms were
      achieved as a function of temperature (120, 150, 200 degrees C) and Hg degrees 
      concentrations (1.0-7.0 mg/m(3)). Experimental runs demonstrated satisfying
      results of the adsorption process, while Langmuir parameters were evaluated with
      gas-solid equilibrium data. Especially, they confirmed that adsorption capacity
      is a favored process in case of lower temperature and they showed that the
      adsorption heat was -20 kJ/mol. Furthermore, a numerical integration of
      differential equations that model the adsorption process was proposed. Scanning
      electron microscopy (SEM) investigation was an useful tool to investigate about
      fresh and saturated carbon areas. The comparison between them allowed
      identification of surface sites where mercury is adsorbed; these spots correspond
      to carbon areas where sulfur concentration is greater. IMPLICATIONS: Mercury
      compounds can cause severe harm to human health and to the ecosystem. There are a
      lot of sources that emit mercury species to the atmosphere; the main ones are
      exhaust gases from coal combustion and municipal solid waste incineration.
      Furthermore, certain CO2 capture processes, particularly oxyfuel combustion in a
      pulverized fuel coal-fired power station, produce a raw CO2 product containing
      several contaminants, mainly water vapor, oxygen, and nitrogen but also mercury,
      that have to be almost completely removed; otherwise these would represent a
      strong drawback to the success of the process.

PMID- 27043168
TI  - Gabapentin: A promising therapy for uremic pruritus in hemodialysis patients: A
      randomized-controlled trial and review of literature.
AB  - BACKGROUND: Treatment of uremic pruritus (UP) is a big challenge. OBJECTIVES: To
      evaluate efficacy, appropriate dosing regimen and safety of gabapentin on UP in
      hemodialysis (HD) patients. PATIENTS AND METHODS: Fifty-four uremic patients
      undergoing HD and complaining of UP were randomly classified into two equal
      groups. Gabapentin group: 27 patients received gabapentin capsules starting with
      100 mg and gradually titrated up to a maximum of 300 mg after each HD session for
      one month. Placebo group: 27 patients received placebo thrice weekly after each
      HD session. Severity of pruritus was measured by visual analog scale (VAS) and 5
      D pruritus scale. RESULTS: In gabapentin group, 88.9% of patients responded well
      to gabapentin versus 22.2% in placebo group. A highly statistical difference was
      detected in favor of gabapentin group (p< 0.001). The frequency of the use of the
      lowest dose (100 mg thrice weekly) was significantly higher than other doses (p <
      0.0001). Adverse effects were mild and tolerated. CONCLUSION: Gabapentin is a
      promising and a well-tolerated treatment option for patients with UP. We
      recommend it as a first line therapy with a maintenance post-HD dose of 100-300
      mg. We also recommend the 5-D scale in the assessment of the severity of
      pruritus.

PMID- 27043169
TI  - Spatial distribution of residual stresses in glass-ZrO2 sphero-cylindrical
      bilayers.
AB  - Residual stresses arising from inhomogeneous cooling after sintering have shown
      to play a preponderant role in the higher incidence of chippings observed for
      glass-zirconia dental prostheses. Still, current descriptions of their nature and
      distribution have failed to reconcile with clinical findings. Therefore, an
      axisymmetric sphero-cylindrical bilayer model was used in this study to determine
      the effect of the cooling rate on the final spatial distribution of residual
      stresses. Zirconia frameworks with two different radii (1.6 and 3.2mm) were
      CAD/CAM fabricated. Subsequent glass overlays with two different thickness ratios
      (1:1 and 2:1) were generated and heat pressed onto the zirconia substrates. The
      obtained structures were submitted to a last firing process and fast- (45 degrees
      C/s) or slow-cooled (0.5 degrees C/s) to room temperature. Unbonded bilayers were
      produced by firing glass overlays onto boron nitride coated zirconia. Thin
      sagittal and transversal sections were obtained from the specimens to assess
      residual stress distribution by means of light birefringence. The applied cooling
      rates did not affect distribution or magnitude of radial residual stresses
      (sagittal sections), whereas increased hoop stress magnitudes were measured
      (transversal sections) in fast-cooled specimens. A distinct stress nature was
      observed for the hoop stress component of unbonded overlays after fast cooling.
      Interaction between stress components seems to govern the final stress
      distribution, highlighting the importance of a multiaxial assessment of this
      problem in three-dimensional structures.

PMID- 27043170
TI  - Appeal of electronic cigarettes in smokers with serious mental illness.
AB  - INTRODUCTION: Up to 75% of people with serious mental illness (SMI) smoke, and
      most are highly dependent on nicotine, consuming more cigarettes per day than
      smokers without mental illness. Even with evidence-based treatment, relapses are
      common, resulting in high morbidity and early mortality from tobacco-related
      diseases. Electronic cigarettes (e-cigarettes) are theoretically safer because
      they deliver no tar or carbon monoxide; however, their appeal is largely untested
      in people with SMI. METHODS: We enrolled 21 chronic smokers with SMI who had
      failed a quit attempt and were not engaged in cessation treatment. Research staff
      provided e-cigarettes and instructions on how to use them, and assessed
      participants weekly for 4weeks. RESULTS: Of the enrolled participants, 19
      completed weekly assessments. From baseline to the final study visit, mean self
      reported use of combustible tobacco declined from 192 to 67cigarettes/week
      (t=3.62, df=17, p=0.005), confirmed by reduction in breath carbon monoxide from
      27ppm to 15ppm (t=3.246, df=18, p=0.004). Use of e-cigarettes did not escalate
      over the 4weeks. Temporary and mild side effects, including dry/sore throat,
      nausea, dizziness, and cough, were reported by 58% of participants. End of trial
      ratings of enjoyment, satisfaction compared to regular cigarettes, and
      willingness to buy e-cigarettes were high (ranging from 3.82-4.51 on a 5-point
      scale). CONCLUSIONS: Results of this study suggest that people with SMI may find
      e-cigarettes an appealing substitute for combustible cigarettes. We found no
      evidence of increasing nicotine dependence. Further randomized studies are needed
      to better assess e-cigarette appeal and toxicity.

PMID- 27043165
TI  - Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.
AB  - BACKGROUND: Antiarrhythmic drugs are used commonly in out-of-hospital cardiac
      arrest for shock-refractory ventricular fibrillation or pulseless ventricular
      tachycardia, but without proven survival benefit. METHODS: In this randomized,
      double-blind trial, we compared parenteral amiodarone, lidocaine, and saline
      placebo, along with standard care, in adults who had nontraumatic out-of-hospital
      cardiac arrest, shock-refractory ventricular fibrillation or pulseless
      ventricular tachycardia after at least one shock, and vascular access. Paramedics
      enrolled patients at 10 North American sites. The primary outcome was survival to
      hospital discharge; the secondary outcome was favorable neurologic function at
      discharge. The per-protocol (primary analysis) population included all randomly
      assigned participants who met eligibility criteria and received any dose of a
      trial drug and whose initial cardiac-arrest rhythm of ventricular fibrillation or
      pulseless ventricular tachycardia was refractory to shock. RESULTS: In the per
      protocol population, 3026 patients were randomly assigned to amiodarone (974),
      lidocaine (993), or placebo (1059); of those, 24.4%, 23.7%, and 21.0%,
      respectively, survived to hospital discharge. The difference in survival rate for
      amiodarone versus placebo was 3.2 percentage points (95% confidence interval
      [CI], -0.4 to 7.0; P=0.08); for lidocaine versus placebo, 2.6 percentage points
      (95% CI, -1.0 to 6.3; P=0.16); and for amiodarone versus lidocaine, 0.7
      percentage points (95% CI, -3.2 to 4.7; P=0.70). Neurologic outcome at discharge
      was similar in the three groups. There was heterogeneity of treatment effect with
      respect to whether the arrest was witnessed (P=0.05); active drugs were
      associated with a survival rate that was significantly higher than the rate with
      placebo among patients with bystander-witnessed arrest but not among those with
      unwitnessed arrest. More amiodarone recipients required temporary cardiac pacing
      than did recipients of lidocaine or placebo. CONCLUSIONS: Overall, neither
      amiodarone nor lidocaine resulted in a significantly higher rate of survival or
      favorable neurologic outcome than the rate with placebo among patients with out
      of-hospital cardiac arrest due to initial shock-refractory ventricular
      fibrillation or pulseless ventricular tachycardia. (Funded by the National Heart,
      Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT01401647.).

PMID- 27043171
TI  - Method for rapid screening analysis of Sr-90 in edible plant samples collected
      near Fukushima, Japan.
AB  - A screening method for measuring (90)Sr in edible plant samples by focusing on
      (90)Y in equilibrium with (90)Sr is reported. (90)Y was extracted from samples
      with acid, co-precipitated with iron hydroxide, and precipitated with oxalic
      acid. The dissolved oxalate precipitate was loaded on an extraction
      chromatography resin, and the (90)Y-enriched eluate was analyzed by Cherenkov
      counting with a TDCR liquid scintillation counter. (90)Sr ((90)Y) concentration
      was determined in plant samples collected near the damaged Fukushima Daiichi
      Nuclear Power Plants with this method.

PMID- 27043172
TI  - Cold-active alkaline phosphatase is irreversibly transformed into an inactive
      dimer by low urea concentrations.
AB  - Alkaline phosphatase is a homodimeric metallo-hydrolase where both Zn(2+) and
      Mg(2+) are important for catalysis and stability. Cold-adapted alkaline
      phosphatase variants have high activity at low temperatures and lower thermal
      stability compared with variants from mesophilic hosts. The instability, and thus
      inactivation, could be due to loose association of the dimers and/or loosely
      bound Mg(2)(+) in the active site, but this has not been studied in detail for
      the cold-adapted variants. Here, we focus on using the intrinsic fluorescence of
      Trp in alkaline phosphatase from the marine bacterium Vibrio splendidus (VAP) to
      probe for dimerization. Trp->Phe substitutions showed that two out of the five
      native Trp residues contributed mostly to the fluorescence emission. One residue,
      15A away from the active site (W460) and highly solvent excluded, was
      phosphorescent and had a distant role in substrate binding. An additional Trp
      residue was introduced to the dimer interface to act as a possible probe for
      dimerization. Urea denaturation curves indicated that an inactive dimer
      intermediate, structurally equivalent to the native state, was formed before
      dimer dissociation took place. This is the first example of the transition of a
      native dimer to an inactive dimer intermediate for alkaline phosphatase without
      using mutagenesis, ligands, or competitive inhibition. 

PMID- 27043173
TI  - Discovery of small-molecule nonpeptide antagonists of nociceptin/orphanin FQ
      receptor: The studies of design, synthesis, and structure-activity relationships
      for (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene]
      derivatives.
AB  - Nociceptin/orphanin FQ (N/OFQ) and N/OFQ peptide (NOP) receptor are expressed and
      distributed in various regions such as central nervous system (CNS), peripheral
      nervous system, immune system, and peripheral tissues. N/OFQ and NOP receptor
      have important roles on a variety of physiological, pathophysiological,
      regulatory, and dysregulatory mechanisms in the living body. Both activation and
      blockade of NOP receptor function have displayed clinical potential of NOP
      receptor agonists and antagonists for the treatment of various diseases or
      pathophysiological conditions, respectively. Potent and selective NOP receptor
      agonists/antagonists are also useful tools to investigate the various mechanisms
      mediated by NOP receptor-N/OFQ system. As the present study, a series of (4
      arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] analogs
      was designed, synthesized, and biologically evaluated in vitro to seek and
      identify potent and selective, small-molecules of nonpeptide NOP receptor
      antagonists, which resulted in the discovery of novel potent small-molecule 15
      with high human NOP receptor selectivity over human MU receptor. The structure
      activity relationship (SAR) of the potency and selectivity, structure-metabolic
      stability relationship (SMR), and SAR of hERG (human ether-a-go-go related gene)
      potassium ion channel binding affinity for the analogs in the present studies in
      vitro provided or suggested significant and/or useful structural determinants and
      insights for the respective purposes. The superior profiles of compound 15 are
      discussed with a viewpoint of multisite interactions between ligand and NOP
      receptor, together with the results of previous NOP receptor agonist/antagonist
      studies. 

PMID- 27043174
TI  - Cytotoxic effects of tebufenozide in vitro bioassays.
AB  - Tebufenozide is considered an environmentally friendly pesticide due to its
      specificity on target insects, but the effects on human are well studied. Studies
      on the toxicity of tebufenozide at molecular and cellular level is poorly
      understood. The present study reveals non-selective cytotoxic effects of
      tebufenozide, and the apoptotic mechanism induced by tebufenozide on HeLa and
      Tn5B1-4 cells. We demonstrate that the viability of HeLa and Tn5B1-4 cells is
      inhibited by tebufenozide in a time- and concentration-dependent manner.
      Intracellular biochemical assays showed that tebufenozide-induced apoptosis of
      two cell lines concurrent with a decrease in the mitochondrial membrane potential
      and an increase reactive oxygen species generation, the release of cytochrome-c
      into the cytosol and a marked activation of caspase-3. These results indicate
      that a mitochondrial-dependent intrinsic pathway contributes to tebufenozide
      induced apoptosis in HeLa and Tn5B1-4 cells and suggests potential threats to
      ecosystems and human health.

PMID- 27043175
TI  - Prospective validation of two mathematical models to calculate the risk of
      endometrial malignancy in patients with postmenopausal bleeding and sonographic
      endometrial thickness >=4.5 mm.
AB  - AIM: To prospectively validate two mathematical models for calculating the
      likelihood of endometrial malignancy in patients with postmenopausal bleeding
      (PMPB), sonographic endometrial thickness (ET) >=4.5 mm and no fluid in the
      uterine cavity. METHODS: This is a prospective observational diagnostic
      validation study performed in a PMPB clinic in a university hospital. Of 860
      consecutive patients, 350 fulfilled our inclusion criteria. A standardized
      history was taken, clinical and transvaginal grey scale and power Doppler
      ultrasound examinations were performed following a research protocol. The
      percentage vascularized area of the endometrium at power Doppler examination (VI)
      was calculated using computer software. The colour content of the endometrial
      scan was estimated subjectively on a visual analogue scale (VAS). Gold standard
      was the histological diagnosis of the endometrium. Main outcome measures were
      area under the receiver operating characteristic curve (AUC), sensitivity and
      specificity when using the cut-offs suggested in the original study, and
      calibration curves. RESULTS: Eighty (23%) patients had malignant endometrium. The
      performance of the models was similar to that in the original study. The model
      including patient's age, use of hormone therapy, ET and VAS performed best (AUC
      0.91; 95% confidence interval [CI] 0.87-0.95; sensitivity 70%, specificity 93%).
      The model including ET, VI, patient's age and hormone therapy use had AUC 0.89
      (95% CI 0.84-0.93; sensitivity 79%; specificity 81%). ET had AUC 0.83 (95% CI
      0.78-0.88). The models were reasonably well calibrated. CONCLUSION: On
      prospective validation both models retained their diagnostic performance. This
      suggests that they are robust and potentially clinically useful for
      individualized patient management.

PMID- 27043176
TI  - Non-microbial sources of microbial volatile organic compounds.
AB  - BACKGROUND: The question regarding the true sources of the purported microbial
      volatile organic compounds (MVOCs) remains unanswered. OBJECTIVE: To identify
      microbial, as well as non-microbial sources of 28 compounds, which are commonly
      accepted as microbial VOCs (i.e. primary outcome of interest is Sigma 28 VOCs).
      METHODS: In a cross-sectional investigation of 390 homes, six building inspectors
      assessed water/mold damage, took air and dust samples, and measured environmental
      conditions (i.e., absolute humidity (AH, g/m(3)), temperature ( degrees C),
      ventilation rate (ACH)). The air sample was analyzed for volatile organic
      compounds (MUg/m(3)) and; dust samples were analyzed for total viable fungal
      concentration (CFU/g) and six phthalates (mg/g dust). Four benchmark variables of
      the underlying sources were defined as highest quartile categories of: 1) the
      total concentration of 17 propylene glycol and propylene glycol ethers (Sigma17
      PGEs) in the air sample; 2) 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (TMPD
      MIB) in the air sample; 3) semi-quantitative mold index; and 4) total fungal load
      (CFU/g). RESULTS: Within severely damp homes, co-occurrence of the highest
      quartile concentration of either Sigma17 PGEs or TMPD-MIB were respectively
      associated with a significantly higher median concentration of Sigma 28 VOCs
      (8.05 and 13.38MUg/m(3), respectively) compared to the reference homes (4.30 and
      4.86MUg/m(3), respectively, both Ps <=0.002). Furthermore, the homes within the
      highest quartile range for Sigma fungal load as well as AH were associated with a
      significantly increased median Sigma 28 VOCs compared to the reference group
      (8.74 vs. 4.32MUg/m(3), P=0.001). Within the final model of multiple indoor
      sources on Sigma 28 VOCs, one natural log-unit increase in summed concentration
      of Sigma17 PGEs, plus TMPD-MIB (Sigma 17 PGEs + TMPD-MIB) was associated with 1.8
      times (95% CI, 1.3-2.5), greater likelihood of having a highest quartile of Sigma
      28 VOCs, after adjusting for absolute humidity, history of repainting at least
      one room, ventilation rate, and mold index (P-value =0.001). Homes deemed
      severely mold damaged (i.e., mold index =1) were associated with 1.7-times (95%
      CI, 0.8-3.6), greater likelihood of having a highest quartile of Sigma 28 VOCs,
      even though such likelihood was not significant (P-value =0.164). In addition,
      absolute humidity appeared to positively interact with mold index to
      significantly elevate the prevalence of the highest quartile category of Sigma 28
      VOCs. CONCLUSION: The indoor concentration of Sigma 28 VOCs, which are widely
      accepted as MVOCs, are significantly associated with the markers of synthetic
      (i.e. Sigma17 PGEs and TMPD-MIB), and to less extent, microbial (i.e., mold
      index) sources.

PMID- 27043177
TI  - Evaluation of advanced cooling therapy's esophageal cooling device for core
      temperature control.
AB  - Managing core temperature is critical to patient outcomes in a wide range of
      clinical scenarios. Previous devices designed to perform temperature management
      required a trade-off between invasiveness and temperature modulation efficiency.
      The Esophageal Cooling Device, made by Advanced Cooling Therapy (Chicago, IL),
      was developed to optimize warming and cooling efficiency through an easy and low
      risk procedure that leverages heat transfer through convection and conduction.
      Clinical data from cardiac arrest, fever, and critical burn patients indicate
      that the Esophageal Cooling Device performs very well both in terms of
      temperature modulation (cooling rates of approximately 1.3 degrees C/hour,
      warming of up to 0.5 degrees C/hour) and maintaining temperature stability
      (variation around goal temperature +/- 0.3 degrees C). Physicians have reported
      that device performance is comparable to the performance of intravascular
      temperature management techniques and superior to the performance of surface
      devices, while avoiding the downsides associated with both. 

PMID- 27043178
TI  - Design, synthesis and antitumor activity of novel pyrazolo[3,4-d]pyrimidine
      derivatives as EGFR-TK inhibitors.
AB  - A novel series of 2-(3,6-dimethyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N
      (4-substitutedbenzylidene)acetohydrazide (12a-g) was prepared and their
      structures were confirmed by spectral and elemental analyses. The cytotoxic
      activity of the newly synthesized compounds was evaluated against breast
      carcinoma (MCF-7), non-small cell lung cancer (A549) and human colorectal
      adenocarcinoma (HT-29) cell lines using MTT and colony formation assays. The
      tested compounds showed a marked anticancer activity against all the tested cell
      lines, especially compound 12g, which was the most potent anticancer agent with
      half maximal inhibitory concentrations (IC50) between 5.36 and 9.09MUM. Docking
      studies into ATP binding site of EGFR protein tyrosine kinase were performed to
      predict their scores and mode of binding to amino acids, In addition, the
      inhibitory activity of the target compounds against epidermal growth factor
      receptor tyrosine kinase (EGFR-TK) was evaluated. Results indicated the ability
      of the target compounds to inhibit EGFR-TK with half maximal inhibitory
      concentrations (IC50) in the range of 4.18-35.88MUM. Furthermore, The most active
      compounds 12g, 12c and 12d were assayed against Fibroblast Growth Factor Receptor
      (FGFR), Insulin Receptor (IR) and Vascular Endothelial Growth Factor Receptor
      (VEGFR). The activity of the reported compounds warrants further optimization as
      novel members in cancer treatment protocols.

PMID- 27043180
TI  - Near-criticality underlies the behavior of early tumor growth.
AB  - The controlling factors that underlie the growth of tumors have often been hard
      to identify because of the presence in this system of a large number of
      intracellular biochemical parameters. Here, we propose a simplifying framework to
      identify the key physical parameters that govern the early growth of tumors. We
      model growth by means of branching processes where cells of different types can
      divide and differentiate. First, using this process that has only one controlling
      parameter, we study a one cell type model and compute the probability for tumor
      survival and the time of tumor extinction. Second, we show that when cell death
      and cell division are perfectly balanced, stochastic effects dominate the growth
      dynamics and the system exhibits a near-critical behavior that resembles a second
      order phase transition. We show, in this near-critical regime, that the time
      interval before tumor extinction is power-law distributed. Finally, we apply this
      branching formalism to infer, from experimental growth data, the number of
      different cell types present in the observed tumor. 

PMID- 27043179
TI  - A C. elegans homolog for the UV-hypersensitivity syndrome disease gene UVSSA.
AB  - The transcription-coupled repair pathway (TC-NER) plays a vital role in removing
      transcription-blocking DNA lesions, particularly UV-induced damage. Clinical
      symptoms of the two TC-NER-deficiency syndromes, Cockayne syndrome (CS) and UV
      hypersensitivity syndrome (UVSS) are dissimilar and the underlying molecular
      mechanism causing this difference in disease pathology is not yet clearly
      understood. UV-stimulated scaffold protein A (UVSSA) has been identified recently
      as a new causal gene for UVSS. Here we describe a functional homolog of the human
      UVSSA gene in the nematode Caenorhabditis elegans, uvs-1 (UVSSA-like-1).
      Mutations in uvs-1 render the animals hypersensitive to UV-B irradiation and
      transcription-blocking lesion-inducing illudin-M, similar to mutations in TC-NER
      deficient mutants. Moreover, we demonstrate that TC-NER factors including UVS-1
      are required for the survival of the adult animals after UV-treatment.

PMID- 27043181
TI  - Scintillating Nanoparticles as Energy Mediators for Enhanced Photodynamic
      Therapy.
AB  - Achieving effective treatment of deep-seated tumors is a major challenge for
      traditional photodynamic therapy (PDT) due to difficulties in delivering light
      into the subsurface. Thanks to their great tissue penetration, X-rays hold the
      potential to become an ideal excitation source for activating photosensitizers
      (PS) that accumulate in deep tumor tissue. Recently, a wide variety of
      nanoparticles have been developed for this purpose. The nanoparticles are
      designed as carriers for loading various kinds of PSs and can facilitate the
      activation process by transferring energy harvested from X-ray irradiation to the
      loaded PS. In this review, we focus on recent developments of nanoscintillators
      with high energy transfer efficiency, their rational designs, as well as
      potential applications in next-generation PDT. Treatment of deep-seated tumors by
      using radioisotopes as an internal light source will also be discussed.

PMID- 27043182
TI  - Dietary Fatty Acids from Leaves of Clerodendrum Volubile Induce Cell Cycle
      Arrest, Downregulate Matrix Metalloproteinase-9 Expression, and Modulate Redox
      Status in Human Breast Cancer.
AB  - The antiproliferative effect of the fatty acid components of Clerodendrum
      volubile leaves as well as its antioxidant effect on MCF-7 and MDA-MB-231 human
      breast cancer cell lines were investigated. Fatty acids extracted from C.
      volubile leaf oil were subjected to gas chromatography mass spectrometry (GCMS)
      analysis. The cells were cultured and treated with the fatty acids for 48 h,
      after which the antiproliferation effect was ascertained via MTT assay and cell
      viability analysis using BD fluorescence activated cells sorting (FACS) Calibur.
      Cell cycle was analyzed by flow cytometry on FACS Calibur. Western blotting was
      used in determining expression of proteins in the cell lines. The treated cell
      lines were assessed for reduced glutathione level, catalase, superoxide
      dismutase, and lipid peroxidation. The fatty acids significantly inhibited cell
      proliferation, arrested G0/G1 phase, downregulated the expression of MMP-9, and
      attenuated oxidative stress in of MCF-7 cell lines but had little or no effect on
      MDA-MB-231 cell lines. These results indicate the therapeutic potential of the
      fatty acids components of the leaves of C. volubile on human breast cancer, which
      may be explored further in drug development.

PMID- 27043183
TI  - Imaging-Based Predictors of Persistent Type II Endoleak After Endovascular
      Abdominal Aortic Aneurysm Repair.
AB  - OBJECTIVE: The purpose of this study is to determine the imaging-based parameters
      associated with the occurrence of persistent type II endoleaks after endovascular
      abdominal aortic aneurysm repair. MATERIALS AND METHODS: We reviewed the imaging
      and clinical data for 47 patients with early-onset type II endoleak after
      endovascular repair. Various predictors of persistent type II endoleaks were
      analyzed on the basis of preoperative CT findings. In addition, the appearance
      time of endoleak cavity on the operative angiogram and the relative attenuation
      of the endoleak cavity in the arterial phase image from the first postoperative
      CT study were analyzed. RESULTS: The early-onset type II endoleak resolved
      spontaneously in 22 patients (i.e., the transient group), whereas it was
      identified on CT studies of the remaining 25 patients 6 months after endovascular
      repair (i.e., the persistent group). The appearance time of the endoleak cavity
      on angiographic examination was significantly shorter in the persistent group
      than in the transient group (mean [+/- SD] appearance time, 4.7 +/- 0.3 s vs 8.8
      +/- 0.3 s). The relative attenuation of the endoleak cavity on the first
      postoperative CT scan was also significantly higher in the persistent group than
      in the transient group (mean, 0.70 +/- 0.03 vs 0.30 +/- 0.04). For each
      parameter, ROC analysis revealed the following cutoff points for predicting
      persistent type II endoleak: 6 seconds for the appearance time of the endoleak
      cavity (sensitivity, 88%; specificity, 86%), and 0.5 for the relative attenuation
      of the endoleak cavity (sensitivity, 80%; specificity, 95%). Evaluation of other
      imaging-based parameters revealed no statistically significant differences
      between the groups. CONCLUSION: The appearance time of the endoleak cavity on the
      final operative angiogram and the attenuation of the endoleak cavity on the first
      postoperative CT scan can be strong imaging-based predictors of persistent type
      II endoleak.

PMID- 27043184
TI  - Predictors of HIV testing among men who have sex with men: a focus on men living
      outside major urban centres in Canada.
AB  - Men who have sex with men (MSM) represent almost half of new HIV infections in
      Canada each year. However, the vast majority of research on HIV testing among MSM
      has been conducted in major urban centres. The present study addressed this gap
      by investigating HIV testing behaviour and predictors of HIV testing among MSM
      living outside major urban centres, in the Interior of British Columbia. An
      anonymous online survey of 153 MSM assessed HIV testing behaviour and
      psychosocial factors that may impact HIV testing (internalized homophobia,
      disclosure to healthcare providers (HCPs) of same sex attraction, and gay
      community involvement). Almost one-quarter (24%) had never been tested and over
      one-third (35%) had not disclosed same sex attraction to HCPs. Internalized
      homophobia was associated with a lower likelihood of HIV testing, and this
      relationship was partially explained by the fact that those high in internalized
      homophobia were less likely to disclose same sex attraction to their HCPs.
      Neither formal nor informal involvement in the gay community was related to HIV
      testing, and both types of involvement were relatively low in our sample. Further
      research is needed to better understand the distinctive health issues facing MSM
      living outside major urban centres. 

PMID- 27043185
TI  - High-frequency oscillatory ventilation versus conventional ventilation for acute
      respiratory distress syndrome.
AB  - BACKGROUND: High-frequency oscillation (HFO) is an alternative to conventional
      mechanical ventilation that is sometimes used to treat people with acute
      respiratory distress syndrome, but effects on oxygenation, mortality and adverse
      clinical outcomes are uncertain. This review was originally published in 2004 and
      was updated in 2013 and again in 2015. OBJECTIVES: To determine the effects of
      HFO compared to conventional mechanical ventilation on physiological outcomes,
      clinical outcomes, and mortality when used for the treatment of acute respiratory
      distress syndrome (ARDS). SEARCH METHODS: We electronically searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (Ovid), MEDLINE (Ovid), EMBASE
      (Ovid), and ISI, from inception to December 2015. We conducted the original
      search in 2002. We manually searched reference lists from included studies and
      review articles; searched conference proceedings of the American Thoracic Society
      (1994 to 2015), Society of Critical Care Medicine (1994 to 2015), European
      Society of Intensive Care Medicine (1994 to 2015), and American College of Chest
      Physicians (1994 to 2015); contacted clinical experts in the field; and searched
      for unpublished and ongoing trials in clinicaltrials.gov and controlled
      trials.com. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing
      treatment using HFO with conventional mechanical ventilation for children and
      adults diagnosed with ARDS. DATA COLLECTION AND ANALYSIS: Three review authors
      independently extracted data on clinical, physiological, and safety outcomes
      according to a predefined protocol. We contacted investigators of all included
      studies to clarify methods and obtain additional data. We used random-effects
      models in the analyses. MAIN RESULTS: We include 10 RCTs (n = 1850); almost all
      participants had moderate or severe ARDS. For the primary analysis, the risk of
      bias was low in three studies and unclear in five studies; the overall quality of
      evidence was very low due to imprecision, inconsistency, indirectness and
      methodologic limitations. In participants randomized to HFO, there was no
      significant difference in hospital or 30-day mortality (risk ratio (RR) 0.92, 95%
      confidence interval (CI) 0.72 to 1.16; P = 0.46, I2 = 66%; 8 trials, 1779
      participants, 807 deaths) compared with conventional ventilation. One large
      multicentre RCT was terminated early because of increased mortality in
      participants randomized to HFO compared to mechanical ventilation with low tidal
      volume and high positive end expiratory pressure, with HFO reserved only as a
      rescue therapy. We found substantial between-trial statistical heterogeneity (I2
      = 0% to 66%) for clinical outcomes, including mortality.  AUTHORS' CONCLUSIONS:
      The findings of this systematic review suggest that HFO does not reduce hospital
      and 30-day mortality due to ARDS; the quality of evidence was very low. Our
      findings do not support the use of HFO as a first-line strategy in people
      undergoing mechanical ventilation for ARDS.

PMID- 27043186
TI  - [Occupational Hearing Loss (BK-No. 2301) - A Retrospective Analysis of 100
      Consecutive Cases].
AB  - Introduction: In order for a diagnosis of Occupational Hearing Loss (BK-no. 2301)
      to be made certain criteria must be fulfilled to establish that the hearing loss
      is occupational in origin. This work compares 2 groups, those who fulfil the
      criteria (BKE) and those who do not (BKNE). Methods: A 100 consecutive reports
      ("Larmgutachten BK-no. 2301") written by the authors were examined
      retrospectively. These recorded audiometric examination, an analysis of any
      tinnitus and noise exposure plus use of hearing protection. Pre- and post-noise
      exposure status together with an expert assessment of work limitations was made
      to produce a 7 point score. Results: 67% of the group fulfilled the conditions
      for occupational hearing loss (9% were entitled to compensation). In the BKE
      group 82% showed typical audiometric signs of noise damage with 75% of them
      fulfilling at least 6 criteria of occupational disease no. 2301. Tinnitus typical
      for noise exposure was found in 26%. Discussion: A 7 point score could be useful
      in the future as a method of helping distinguish hearing loss and tinnitus from
      occupational as opposed to other causes.

PMID- 27043187
TI  - Stigmatizing Beliefs Regarding Street-Connected Children and Youth: Criminalized
      Not Criminal.

PMID- 27043188
TI  - Limiting the Duration of Opioid Prescriptions: Balancing Excessive Prescribing
      and the Effective Treatment of Pain.

PMID- 27043190
TI  - Decoding Polo-like kinase 1 signaling along the kinetochore-centromere axis.
AB  - Protein kinase signaling along the kinetochore-centromere axis is crucial to
      assure mitotic fidelity, yet the details of its spatial coordination are obscure.
      Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis
      control signaling events to elicit mitotic functions. To do this, we restricted
      active Plk1 to discrete subcompartments within the kinetochore-centromere axis
      using chemical genetics and decoded functional and phosphoproteomic signatures of
      each. We observe distinct phosphoproteomic and functional roles, suggesting that
      Plk1 exists and functions in discrete pools along this axis. Deep within the
      centromere, Plk1 operates to assure proper chromosome alignment and segregation.
      Thus, Plk1 at the kinetochore is a conglomerate of an observable bulk pool
      coupled with additional functional pools below the threshold of microscopic
      detection or resolution. Although complex, this multiplicity of locales provides
      an opportunity to decouple functional and phosphoproteomic signatures for a
      comprehensive understanding of Plk1's kinetochore functions.

PMID- 27043189
TI  - Raft-based interactions of gangliosides with a GPI-anchored receptor.
AB  - Gangliosides, glycosphingolipids containing one or more sialic acid(s) in the
      glyco-chain, are involved in various important physiological and pathological
      processes in the plasma membrane. However, their exact functions are poorly
      understood, primarily because of the scarcity of suitable fluorescent ganglioside
      analogs. Here, we developed methods for systematically synthesizing analogs that
      behave like their native counterparts in regard to partitioning into raft-related
      membrane domains or preparations. Single-fluorescent-molecule imaging in the live
      cell plasma membrane revealed the clear but transient colocalization and
      codiffusion of fluorescent ganglioside analogs with a fluorescently labeled
      glycosylphosphatidylinisotol (GPI)-anchored protein, human CD59, with lifetimes
      of 12 ms for CD59 monomers, 40 ms for CD59's transient homodimer rafts in
      quiescent cells, and 48 ms for engaged-CD59-cluster rafts, in cholesterol- and
      GPI-anchoring-dependent manners. The ganglioside molecules were always mobile in
      quiescent cells. These results show that gangliosides continually and dynamically
      exchange between raft domains and the bulk domain, indicating that raft domains
      are dynamic entities.

PMID- 27043191
TI  - Pleural gas analysis for the identification of alveolopleural fistulae.
AB  - PURPOSE OF REVIEW: The method for identification of alveolopleural fistulae (APF)
      by visual inspection of air bubbles in the chest drainage system has several
      limitations and suffers from poor accuracy. Here we discuss the use of a novel
      technique of pleural gas analysis in the identification and management of APF.
      RECENT FINDINGS: We found that pleural gas analysis has higher sensitivity and
      specificity than visual inspection in identifying APF. Additionally, we
      demonstrated that intrapleural gas milieu impacts lung healing and reduction of
      intrapleural carbon dioxide can promote resolution of APF. SUMMARY: Pleural gas
      analysis is a novel technique to identify and manage APF. Integration of gas
      analysis in chest drainage systems would provide a more objective method for
      managing chest tubes and providing a favorable pleural gas environment for lung
      healing.

PMID- 27043192
TI  - Clinical Features and Prognostic Factors of Patients With Nerve Sheath Tumors in
      the Cervical Spine.
AB  - STUDY DESIGN: A retrospective study was performed. OBJECTIVE: The aim of the
      study was to illustrate the long-term follow-up results and discuss the possible
      factors that may affect outcomes of patients with cervical spinal nerve sheath
      tumors (CSNSTs). SUMMARY OF BACKGROUND DATA: Nerve sheath tumors are the most
      common neoplasms in the spine, but minimal information was published in the
      literature, especially when regarding to prognostic factors due to the benign
      nature. The objective of our study was to present long-term follow-up results and
      discuss the possible factors that may affect outcomes of patients with CSNSTs.
      METHODS: A retrospective analysis of patients with CSNSTs was performed by
      survival analysis. The local relapse-free survival (LRFS) and overall survival
      (OS) rates were estimated using the Kaplan-Meier method to identify potential
      prognostic factors. Factors with P values <=0.1 were subjected to multivariate
      analysis by Cox regression analysis. P values <=0.05 were considered
      statistically significant. RESULTS: A total of 169 patients with CSNSTs were
      included in the study. All patients received surgical treatment. The mean follow
      up period was 72.1 months (median 62.0, range 1-158). Local recurrence was
      detected in 14 patients after surgery in our center, whereas death occurred in 9
      patients with a mean follow-up of 27.2 months (median 24, range 1-84). The
      statistical analyses suggested that resection mode and pathology type were
      independent prognostic factors for LRFS and OS. In addition, postoperative
      recurrence was an adverse independent factor to OS. CONCLUSION: Total resection
      could significantly improve the LRFS and OS for patients with CSNSTs, whereas
      malignant CSNST was associated with worse prognosis. Moreover, postoperative
      recurrence was an adverse independent factor to OS. LEVEL OF EVIDENCE: 4.

PMID- 27043193
TI  - ISSLS Prize Winner: Vibration Really Does Disrupt the Disc: A Microanatomical
      Investigation.
AB  - STUDY DESIGN: Microstructural investigation of vibration-induced disruption of
      the flexed lumbar disc. OBJECTIVE: The aim of the study was to explore micro
      level structural damage in motion segments subjected to vibration at subcritical
      peak loads. SUMMARY OF BACKGROUND DATA: Epidemiological evidence suggests that
      cumulative whole body vibration may damage the disc and thus play an important
      role in low back pain. In vitro investigations have produced herniations via
      cyclic loading (and cyclic with added vibrations as an exacerbating exposure),
      but offered only limited microstructural analysis. METHODS: Twenty-nine healthy
      mature ovine lumbar motion segments flexed 7 degrees  and subjected to vibration
      loading (1300 +/- 500 N) in a sinusoidal waveform at 5 Hz to simulate moderately
      severe physiologic exposure. Discs were tested either in the range of 20,000 to
      48,000 cycles (medium dose) or 70,000 to 120,000 cycles (high dose). Damaged
      discs were analyzed microstructurally. RESULTS: There was no large drop in
      displacement over the duration of both vibration doses indicating an absence of
      catastrophic failure in all tests. The tested discs experienced internal damage
      that included delamination and disruption to the inner and mid-annular layers as
      well as diffuse tracking of nucleus material, and involved both the posterior and
      anterior regions. Less frequent tearing between the inner disc and endplate was
      also observed. Annular distortions also progressed into a more severe form of
      damage, which included intralamellar tearing and buckling and obvious strain
      distortion around the bridging elements within the annular wall. CONCLUSION:
      Vibration loading causes delamination and disruption of the inner and mid-annular
      layers and limited diffuse tracking of nucleus material. These subtle levels of
      disruption could play a significant role in initiating the degenerative cascade
      via micro-level disruption leading to cell death and altered nutrient pathways.
      LEVEL OF EVIDENCE: 5.

PMID- 27043194
TI  - An 11-Year Review of the TARP Procedure in the Treatment of Atlantoaxial
      Dislocation.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of the study was to
      introduce the surgical techniques and evaluate the clinical outcomes of transoral
      atlantoaxial reduction plate (TARP) for the treatment of atlantoaxial
      dislocation. SUMMARY OF BACKGROUND DATA: Researchers have reported on transoral
      plate internal fixation for the treatment of irreducible atlantoaxial dislocation
      (IAAD) without long-term follow-up and detailed clinical experience. METHODS: The
      clinical records of 388 patients with atlantoaxial dislocation (IAAD, 340 cases;
      fixed atlantoaxial dislocation [FAAD], 48 cases) who received the TARP procedure
      from April 2003 to September 2014 were retrospectively reviewed. They were
      treated separately with TARP-I or TARP-II (82 cases), TARP-III (248 cases), or
      TARP-IV (58 cases). X-ray and magnetic resonance imaging were used to evaluate
      the efficacy of reduction and the degree of decompression, respectively. The long
      term clinical outcome was evaluated by Japanese Orthopaedic Association scoring
      and the Symon and Lavender standard. RESULTS: Immediate reduction was achieved
      for all the patients with IAAD (340/340), whereas anatomical reduction was
      achieved for 98.2% of patients (334/340). Anatomical reduction was achieved in
      87.5% of patients with FAAD (42/48). The average degree of spinal cord
      decompression ranged from 75% to 100% with an average of 88.4%. The clinical data
      of 106 patients were evaluated in the latest follow-up (12-108 mo, average 60.5
      mo). The average spinal cord improvement rate by Japanese Orthopaedic Association
      scoring was 62.1%. According to the Symon and Lavender standard, there were 85
      cases rated as markedly effective, 104 cases as effective, and 2 cases as
      noneffective. The overall markedly effective rate was 80% and the effective rate
      was 98%. CONCLUSION: The TARP procedure showed good anterior atlantoaxial
      release, reduction, decompression, and internal fixation for patients with IAAD
      and FAAD through a single anterior approach. It has the advantages of three
      dimensional immediate atlantoaxial reduction and sufficient decompression. LEVEL
      OF EVIDENCE: 3.

PMID- 27043195
TI  - Does Tobacco Use Attenuate Benefits of Early Decompression in Patients With
      Cervical Myelopathy?
AB  - STUDY DESIGN: A retrospective cohort. OBJECTIVE: This study investigates the
      interplay between duration of preoperative symptoms and smoking status with
      respect to postoperative outcomes in patients with cervical spondylotic
      myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Many studies have established the
      harms of smoking and several have identified the benefits of early decompression
      in patients with cervical myelopathy, but to our knowledge, none have assessed
      the relationship between these two variables. METHODS: The medical records of all
      212 patients operated on by the senior author between March 2005 and July 2012
      were reviewed. Inclusion criteria were the diagnosis of CSM with a Nurick score,
      surgical intervention, and at least 2 years of follow-up. Patients were
      categorized according to smoking status and quantification of tobacco use by
      packs per day and pack-years, and duration of symptoms according to thresholds of
      6, 12, or 24 months. Age, sex, preoperative Nurick score, duration of
      preoperative symptoms, duration of follow-up, procedure performed, prior surgery,
      number of levels operated on, diabetes status, ethanol use, and signal change on
      preoperative magnetic resonance imaging were also recorded for ordered logistical
      regression analysis. RESULTS: One hundred twenty-five patients met all criteria.
      Eighty patients were smokers and 45 were nonsmokers. The median change in Nurick
      score for nonsmokers was 2 compared with 1 in smokers. Nonsmokers had a
      statistically significant likelihood of decreased change in Nurick score for
      symptom duration of greater than 24 months (odds ratio = 0.06, P = 0.0025).
      Smokers did not show a significant difference in the change in Nurick score for
      any threshold of symptom duration. CONCLUSION: Increased duration of symptoms
      significantly affects outcomes in surgical decompression of CSM. A history of
      cigarette use may attenuate the benefit of early decompression and results in
      lower improvement in Nurick score regardless of symptom duration. LEVEL OF
      EVIDENCE: 3.

PMID- 27043196
TI  - Electrical generation and control of the valley carriers in a monolayer
      transition metal dichalcogenide.
AB  - Electrically controlling the flow of charge carriers is the foundation of modern
      electronics. By accessing the extra spin degree of freedom (DOF) in electronics,
      spintronics allows for information processes such as magnetoresistive random
      access memory. Recently, atomic membranes of transition metal dichalcogenides
      (TMDCs) were found to support unequal and distinguishable carrier distribution in
      different crystal momentum valleys. This valley polarization of carriers enables
      a new DOF for information processing. A variety of valleytronic devices such as
      valley filters and valves have been proposed, and optical valley excitation has
      been observed. However, to realize its potential in electronics it is necessary
      to electrically control the valley DOF, which has so far remained a significant
      challenge. Here, we experimentally demonstrate the electrical generation and
      control of valley polarization. This is achieved through spin injection via a
      diluted ferromagnetic semiconductor and measured through the helicity of the
      electroluminescence due to the spin-valley locking in TMDC monolayers. We also
      report a new scheme of electronic devices that combine both the spin and valley
      DOFs. Such direct electrical generation and control of valley carriers opens up
      new dimensions in utilizing both the spin and valley DOFs for next-generation
      electronics and computing.

PMID- 27043197
TI  - Digitally encoded DNA nanostructures for multiplexed, single-molecule protein
      sensing with nanopores.
AB  - The simultaneous detection of a large number of different analytes is important
      in bionanotechnology research and in diagnostic applications. Nanopore sensing is
      an attractive method in this regard as the approach can be integrated into small,
      portable device architectures, and there is significant potential for detecting
      multiple sub-populations in a sample. Here, we show that highly multiplexed
      sensing of single molecules can be achieved with solid-state nanopores by using
      digitally encoded DNA nanostructures. Based on the principles of DNA origami, we
      designed a library of DNA nanostructures in which each member contains a unique
      barcode; each bit in the barcode is signalled by the presence or absence of
      multiple DNA dumbbell hairpins. We show that a 3-bit barcode can be assigned with
      94% accuracy by electrophoretically driving the DNA structures through a solid
      state nanopore. Select members of the library were then functionalized to detect
      a single, specific antibody through antigen presentation at designed positions on
      the DNA. This allows us to simultaneously detect four different antibodies of the
      same isotype at nanomolar concentration levels.

PMID- 27043198
TI  - Ultrafast proton transport in sub-1-nm diameter carbon nanotube porins.
AB  - Proton transport plays an important role in many biological processes due to the
      ability of protons to rapidly translocate along chains of hydrogen-bonded water
      molecules. Molecular dynamics simulations have predicted that confinement in
      hydrophobic nanochannels should enhance the rate of proton transport. Here, we
      show that 0.8-nm-diameter carbon nanotube porins, which promote the formation of
      one-dimensional water wires, can support proton transport rates exceeding those
      of bulk water by an order of magnitude. The transport rates in these narrow
      nanotube pores also exceed those of biological channels and Nafion. With larger
      1.5-nm-diameter nanotube porins, proton transport rates comparable to bulk water
      are observed. We also show that the proton conductance of these channels can be
      modulated by the presence of Ca(2+) ions. Our results illustrate the potential of
      small-diameter carbon nanotube porins as a proton conductor material and suggest
      that strong spatial confinement is a key factor in enabling efficient proton
      transport.

PMID- 27043199
TI  - Wafer-scale monodomain films of spontaneously aligned single-walled carbon
      nanotubes.
AB  - The one-dimensional character of electrons, phonons and excitons in individual
      single-walled carbon nanotubes leads to extremely anisotropic electronic, thermal
      and optical properties. However, despite significant efforts to develop ways to
      produce large-scale architectures of aligned nanotubes, macroscopic
      manifestations of such properties remain limited. Here, we show that large
      (>cm(2)) monodomain films of aligned single-walled carbon nanotubes can be
      prepared using slow vacuum filtration. The produced films are globally aligned
      within +/-1.5 degrees  (a nematic order parameter of ~1) and are highly packed,
      containing 1 * 10(6) nanotubes in a cross-sectional area of 1 MUm(2). The method
      works for nanotubes synthesized by various methods, and film thickness is
      controllable from a few nanometres to ~100 nm. We use the approach to create
      ideal polarizers in the terahertz frequency range and, by combining the method
      with recently developed sorting techniques, highly aligned and chirality-enriched
      nanotube thin-film devices. Semiconductor-enriched devices exhibit polarized
      light emission and polarization-dependent photocurrent, as well as anisotropic
      conductivities and transistor action with high on/off ratios.

PMID- 27043200
TI  - Glycomimetic-based pharmacological chaperones for lysosomal storage disorders:
      lessons from Gaucher, GM1-gangliosidosis and Fabry diseases.
AB  - Lysosomal storage disorders (LSDs) are often caused by mutations that destabilize
      native folding and impair the trafficking of enzymes, leading to premature
      endoplasmic reticulum (ER)-associated degradation, deficiencies of specific
      hydrolytic functions and aberrant storage of metabolites in the lysosomes. Enzyme
      replacement therapy (ERT) and substrate reduction therapy (SRT) are available for
      a few of these conditions, but most remain orphan. A main difficulty is that
      virtually all LSDs involve neurological decline and neither proteins nor the
      current SRT drugs can cross the blood-brain barrier. Twenty years ago a new
      therapeutic paradigm better suited for neuropathic LSDs was launched, namely
      pharmacological chaperone (PC) therapy. PCs are small molecules capable of
      binding to the mutant protein at the ER, inducing proper folding, restoring
      trafficking and increasing enzyme activity and substrate processing in the
      lysosome. In many LSDs the mutated protein is a glycosidase and the accumulated
      substrate is an oligo- or polysaccharide or a glycoconjugate, e.g. a
      glycosphingolipid. Although it might appear counterintuitive, substrate analogues
      (glycomimetics) behaving as competitive glycosidase inhibitors are good
      candidates to perform PC tasks. The advancements in the knowledge of the
      molecular basis of LSDs, including enzyme structures, binding modes, trafficking
      pathways and substrate processing mechanisms, have been put forward to optimize
      PC selectivity and efficacy. Moreover, the chemical versatility of glycomimetics
      and the variety of structures at hand allow simultaneous optimization of
      chaperone and pharmacokinetic properties. In this Feature Article we review the
      advancements made in this field in the last few years and the future outlook
      through the lessons taught by three archetypical LSDs: Gaucher disease, GM1
      gangliosidosis and Fabry disease. 

PMID- 27043201
TI  - Single-Ion Block Copoly(ionic liquid)s as Electrolytes for All-Solid State
      Lithium Batteries.
AB  - Polymer electrolytes have been proposed as replacement for conventional liquid
      electrolytes in lithium-ion batteries (LIBs) due to their intrinsic enhanced
      safety. Nevertheless, the power delivery of these materials is limited by the
      concentration gradient of the lithium salt. Single-ion conducting
      polyelectrolytes represent the ideal solution since their nature prevents
      polarization phenomena. Herein, the preparation of a new family of single-ion
      conducting block copolymer polyelectrolytes via reversible addition-fragmentation
      chain transfer polymerization technique is reported. These copolymers comprise
      poly(lithium 1-[3-(methacryloyloxy)propylsulfonyl]-1
      (trifluoromethylsulfonyl)imide) and poly(ethylene glycol) methyl ether
      methacrylate blocks. The obtained polyelectrolytes show low Tg values in the
      range of -61 to 0.6  degrees C, comparatively high ionic conductivity (up to 2.3
      * 10(-6) and 1.2 * 10(-5) S cm(-1) at 25 and 55  degrees C, respectively), wide
      electrochemical stability (up to 4.5 V versus Li(+)/Li), and a lithium-ion
      transference number close to unity (0.83). Owing to the combination of all
      mentioned properties, the prepared polymer materials were used as solid
      polyelectrolytes and as binders in the elaboration of lithium-metal battery
      prototypes with high charge/discharge efficiency and excellent specific capacity
      (up to 130 mAh g(-1)) at C/15 rate.

PMID- 27043202
TI  - Overhead Bryant's Traction Does Not Improve the Success of Closed Reduction or
      Limit AVN in Developmental Dysplasia of the Hip.
AB  - BACKGROUND: Preoperative Bryant's overhead traction before closed reduction (CR)
      in developmental dysplasia of the hip (DDH) remains controversial and its success
      in increasing CR rates and reducing avascular necrosis (AVN) rates has not been
      specifically reported in a large cohort. METHODS: IRB-approved retrospective
      study of patients (below 3 y)who were treated with attempted CR for idiopathic
      DDH from 1980 to 2009. Successful CR was defined as a hip that remained reduced
      and did not require repeat CR or open reduction. Patients were grouped by age,
      hip instability [Ortolani positive (reducible) vs. fixed dislocation], and Tonnis
      classification and rates of successful CR were compared between groups with
      P<0.05. RESULTS: A total of 342 hips were included with a mean age of 0.9 years
      (0.2 to 2.8 y) and a mean follow-up of 10.4 years (2.0 to 27.7 y). There were 269
      hips with fixed dislocations and 73 Ortolani-positive hips. Traction was used in
      276 hips. There was no difference in traction utilization in the 3 age groups
      (below 1, below 1.5, and below 2 y) for either Ortolani-positive hips (P=0.947)
      or fixed dislocations (P=0.943). There was no difference in achieving a
      successful CR comparing traction (60.9%) and no-traction groups (60.6%) (P=1.00).
      For Ortolani-positive hips, traction did not improve the incidence of a
      successful CR for any age group: below 1 year: P=0.19; below 1.5 years: P=0.23;
      and below 2 years: P=0.25. Similarly, fixed dislocation patients had no benefit
      from traction: below 1 year: P=0.76; below 1.5 years: P=0.82; and below 2 years:
      P=0.85. Tonnis classification did predict success of CR but had no influence on
      traction success. There was no difference in the rate of AVN between the traction
      (18%) and no-traction (8%) groups for all patients (P=0.15). CONCLUSIONS: In this
      retrospective series, preoperative Bryant's traction does not improve the rate of
      a successful CR for patients with DDH and has no protective effect on the
      development of AVN of the femoral head. These results suggest that Bryant's
      overhead traction may not be warranted for patients below 3 years of age with
      DDH. LEVEL OF EVIDENCE: Level III.

PMID- 27043203
TI  - A Comparison of SHILLA GROWTH GUIDANCE SYSTEM and Growing Rods in the Treatment
      of Spinal Deformity in Children Less Than 10 Years of Age.
AB  - BACKGROUND: The purpose of this study was to compare the outcomes of the SHILLA
      GROWTH GUIDANCE SYSTEM and "intermittent distraction growing rod" (IDGR) in the
      treatment of children (less than 10 y of age) with progressive spinal deformity.
      This was a multicenter retrospective study of the SHILLA used as an alternative
      treatment to IDGR to support an HDE submission for Food and Drug Administration
      approval. METHODS: Inclusion criteria were progressive scoliosis in a patient
      less than 10 years of age at index procedure. The study population consisted of
      19 SHILLA and 6 IDGR patients whose mean age was 6.1 and 5.8 years, respectively.
      Group demographics were similar between the 2 groups. RESULTS: The initial major
      curve magnitude was 70.3 degrees for SHILLA and 68.3 degrees for IDGR, which
      decreased postoperatively to 22.4 degrees (68.1% improvement) and 32.2 degrees
      (52.9% improvement). During the first 4 years the correction for SHILLA varied
      from 40.5% to 53.4% and for IDGR from 40.9% to 56.9%. At last follow-up, T1-S1
      length was 32.9 cm for SHILLA (4.2 increase from preoperation) and 34.0 cm (5.0
      cm increase from preoperation) for IDGR. Average growth per month from T1-S1:
      SHILLA 0.14 cm, IDGR 0.11 cm. Sagittal T2-T12 preoperatively was 36.3 degrees for
      SHILLA and 30.0 degrees for IDGR. There were 29 reoperations in 12 of the 19
      SHILLA patients (63.2%) and 40 reoperations in all 6 of the IDGR patients (100%)
      related to the index procedure. CONCLUSIONS: The SHILLA GROWTH GUIDANCE SYSTEM
      compares favorably with traditional IDGR constructs in terms of correction of the
      major curve, spinal length and growth, and maintenance of sagittal alignment. The
      >4-fold decrease in additional surgeries makes the SHILLA an attractive
      alternative to minimize comorbidities associated with additional surgeries.
      LEVELS OF EVIDENCE: Level III.

PMID- 27043204
TI  - Translating diagnostic assays from the laboratory to the clinic: analytical and
      clinical metrics for device development and evaluation.
AB  - As lab-on-a-chip health diagnostic technologies mature, there is a push to
      translate them from the laboratory to the clinic. For these diagnostics to
      achieve maximum impact on patient care, scientists and engineers developing the
      tests should understand the analytical and clinical statistical metrics that
      determine the efficacy of the test. Appreciating and using these metrics will
      benefit test developers by providing consistent measures to evaluate analytical
      and clinical test performance, as well as guide the design of tests that will
      most benefit clinicians and patients. This paper is broken into four sections
      that discuss metrics related to general stages of development including: (1)
      laboratory assay development (analytical sensitivity, limit of detection,
      analytical selectivity, and trueness/precision), (2) pre-clinical development
      (diagnostic sensitivity, diagnostic specificity, clinical cutoffs, and receiver
      operator curves), (3) clinical use (prevalence, predictive values, and likelihood
      ratios), and (4) case studies from existing clinical data for tests relevant to
      the lab-on-a-chip community (HIV, group A strep, and chlamydia). Each section
      contains definitions of recommended statistical measures, as well as examples
      demonstrating the importance of these metrics at various stages of the
      development process. Increasing the use of these metrics in lab-on-a-chip
      research will improve the rigor of diagnostic performance reporting and provide a
      better understanding of how to design tests that will ultimately meet clinical
      needs. 

PMID- 27043205
TI  - Protein and Bacterial Antifouling Behavior of Melt-Coextruded Nanofiber Mats.
AB  - Antifouling surfaces are important for biomedical devices to prevent secondary
      infections and mitigate the effects of the foreign body response. Herein, we
      describe melt-coextruded poly(epsilon-caprolactone) (PCL) nanofiber mats grafted
      with antifouling polymers. Nonwoven PCL fiber mats are produced using a
      multilayered melt coextrusion process followed by high-pressure hydroentanglement
      to yield porous patches. The resulting fiber mats show submicrometer cross
      sectional fiber dimensions and yield pore sizes that were nearly uniform, with a
      mean pore size of 1.6 +/- 0.9 MUm. Several antifouling polymers, including
      hydrophilic, zwitterionic, and amphipathic molecules, are grafted to the surface
      of the mats using a two-step procedure that includes photochemistry followed by
      the copper-catalyzed azide-alkyne cycloaddition reaction. Fiber mats are
      evaluated using separate adsorption tests for serum proteins and E. coli. The
      results indicate that poly(oligo(ethylene glycol) methyl ether methacrylate)-co
      (trifluoroethyl methacrylate) (poly(OEGMEMA-co-TFEMA)) grafted mats exhibit
      approximately 85% less protein adhesion and 97% less E. coli adsorption when
      compared to unmodified PCL fibermats. In dynamic antifouling testing, the
      amphiphilic fluorous polymer surface shows the highest flux and highest rejection
      value of foulants. The work presented within has implications on the high
      throughput production of antifouling microporous patches for medical
      applications. 

PMID- 27043206
TI  - Myasthenia Gravis Treated With Autologous Hematopoietic Stem Cell
      Transplantation.
AB  - IMPORTANCE: Some patients with myasthenia gravis (MG) do not respond to
      conventional treatment and have severe or life-threatening symptoms. Alternate
      and emerging therapies have not yet proved consistently or durably effective.
      Autologous hematopoietic stem cell transplant (HSCT) has been effective in
      treating other severe autoimmune neurologic conditions and may have similar
      application in MG. OBJECTIVE: To report 7 cases of severe MG treated with
      autologous HSCT in which consistent, durable, symptom-free, and treatment-free
      remission was achieved. DESIGN, SETTING, AND PARTICIPANTS: This retrospective
      cohort study reports outcomes at The Ottawa Hospital, a large, Canadian, tertiary
      care referral center with expertise in neurology and HSCT, from January 1, 2001,
      through December 31, 2014, with a median follow-up of 40 months (range, 29-149
      months). Data collection and analysis were performed from February 1 through
      August 31, 2015. All patients with MG treated with autologous HSCT at The Ottawa
      Hospital were included. All had persistent severe or life-threatening MG-related
      symptoms despite continued use of intensive immunosuppressive therapies.
      INTERVENTIONS: Autologous hematopoietic stem cell grafts were mobilized with
      cyclophosphamide and granulocyte colony-stimulating factor, collected by
      peripheral blood leukapheresis, and purified away from contaminating lymphocytes
      using CD34 immunomagnetic selection. Patients were treated with intensive
      conditioning chemotherapy regimens to destroy the autoreactive immune system
      followed by graft reinfusion for blood and immune reconstitution. MAIN OUTCOMES
      AND MEASURES: The primary outcome was MG disease activity after autologous HSCT
      measured by frequency of emergency department visits and hospitalizations and
      Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA
      therapy status, and MGFA postintervention status. Safety outcomes included all
      severe autologous HSCT-related complications. RESULTS: Seven patients underwent
      autologous HSCT, 6 for MG and 1 for follicular lymphoma with coincident active
      MG. Mean (SD) ages at MG diagnosis and at autologous HSCT were 37 (11) and 44
      (10) years, respectively. Five patients (71%) had concurrent autoimmune or
      lymphoproliferative illnesses related to immune dysregulation. All patients had
      distinct clinical and electromyographic evidence of MG (MGFA clinical
      classification IIIb-V). All patients achieved durable MGFA complete stable
      remission with no residual MG symptoms and freedom from any ongoing MG therapy
      (MGFA postintervention status of complete stable remission). Three patients (43%)
      experienced transient viral reactivations, and 1 (14%) developed a secondary
      autoimmune disease after autologous HSCT, all of which resolved or stabilized
      with treatment. There were no treatment- or MG-related deaths. CONCLUSIONS AND
      RELEVANCE: Autologous HSCT results in long-term symptom- and treatment-free
      remission in patients with severe MG. The application of autologous HSCT for this
      and other autoimmune neurologic conditions warrants prospective study.

PMID- 27043207
TI  - A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood
      Derived Endothelial Progenitor Cell Immaturity.
AB  - Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial
      Progenitor Cells (EPCs) progeny, display phenotypic and functional
      characteristics of endothelial cells while retaining features of stem/progenitor
      cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and
      proliferative potentials and they can acquire different endothelial phenotypes,
      this requiring some plasticity. These properties provide angiogenic and vascular
      repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree
      of immaturity retained by EPCs is still confused and poorly defined.
      Consequently, to better characterize CB-ECFC stemness, we quantified their
      clonogenic potential and demonstrated that they were reprogrammed into induced
      pluripotent stem cells (iPSCs) more efficiently and rapidly than adult
      endothelial cells. Moreover, we analyzed the transcriptional profile of a broad
      gene panel known to be related to stem cells. We showed that, unlike mature
      endothelial cells, CB-ECFCs expressed genes involved in the maintenance of
      embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results
      provide further evidence and tools to appreciate EPC-derived cell stemness.
      Moreover this novel stem cell transcriptional signature of ECFCs could help
      better characterizing and ranging EPCs according to their immaturity profile. 

PMID- 27043208
TI  - Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of
      13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection.
AB  - Respiratory viruses are among the most important causes of human morbidity and
      mortality worldwide, especially for infants and young children. In the past
      years, a few commercial multiplex RT-PCR assays have been used to detect
      respiratory viruses in spite of the high cost. In the present study, an improved
      single-tube multiplex reverse transcription PCR assay for simultaneous detection
      of 13 respiratory viruses was evaluated and compared with a previously reported
      two-tube assay as the reference method using clinical nasopharyngeal aspirates
      samples. Of 310 prospectively tested respiratory specimens selected from children
      hospitalized with acute respiratory illness, 226 (72.90%, 226/310) and 214
      (69.03%, 214/310) positive for one or more viruses were identified by the single
      tube and the two-tube assays, respectively, with combined test results showing
      good concordance (Kappa value = 0.874). Individually, the single-tube assay for
      adenovirus (Adv), human metapneumovirus (HMPV), human rhinovirus (HRV),
      parainfluenza virus type 1 (PIV1), parainfluenza virus type 3 (PIV3) and
      parainfluenza virus type 4 (PIV4) showed the significantly superior sensitivities
      to those of the two-tube assay. No false positives were found. In conclusion, our
      results demonstrates the one-tube assay revealed significant improvements over
      the two-tube assay in terms of the better sensitivity, more accurate quality
      control, less nonspecific amplification, more cost-effective and shorter turn
      around time and will be a valuable tool for routine surveillance of respiratory
      virus infection in China. 

PMID- 27043209
TI  - Oceanic Distribution, Behaviour, and a Winter Aggregation Area of Adult Atlantic
      Sturgeon, Acipenser oxyrinchus oxyrinchus, in the Bay of Fundy, Canada.
AB  - Seasonal distribution of adult Atlantic sturgeon was examined using pop-up
      satellite archival tags (PSATs) and ultrasonic transmitters deployed in the Saint
      John River, New Brunswick, Canada. Seven MK10 PSATs programmed for release in
      June 2012 and seven MiniPAT PSATs programmed for release in February and April
      2013 were deployed in August 2011 and 2012, respectively. Eleven of 14 PSATs
      surfaced and transmitted depth and temperature data archived for the duration of
      their deployment (121-302 days). Among these eleven PSATs, five were recovered
      and 15-sec archival data was downloaded. Following exit from the Saint John River
      in the fall, tagged fish occupied a mean monthly depth of 76.3-81.6 m at
      temperatures as low as 4.9C throughout the winter before returning to shallower
      areas in the spring. The majority of ultrasonic detections occurred in the Bay of
      Fundy, but fish were detected as far as Riviere Saint-Jean, Quebec, approximately
      1500 km from the Bay of Fundy (representing long-distance migratory rates of up
      to 44 km/day). All PSATs were first detected in the Bay of Fundy. Tags that
      released in February and April were found 5-21 km offshore of the Saint John
      Harbour, while tags that released in June were first detected in near shore areas
      throughout the Bay of Fundy. The substrate at winter tag release locations
      (estimated from backward numerical particle-tracking experiments) consisted
      primarily of moraines and postglacial mud substrate with low backscatter
      strength, indicative of soft or smooth seabed. Based on the proximity of winter
      tag release locations, the consistent depths observed between fish, and previous
      research, it is suspected that a winter aggregation exists in the Bay of Fundy.
      This study expands the understanding of the marine distribution and range of
      Atlantic sturgeon on the east coast of Canada.

PMID- 27043210
TI  - Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein
      Interaction Interfaces.
AB  - Recently it has been shown that cancer mutations selectively target protein
      protein interactions. We hypothesized that mutations affecting distinct protein
      interactions involving established cancer genes could contribute to tumor
      heterogeneity, and that novel mechanistic insights might be gained into
      tumorigenesis by investigating protein interactions under positive selection in
      cancer. To identify protein interactions under positive selection in cancer, we
      mapped over 1.2 million nonsynonymous somatic cancer mutations onto 4,896
      experimentally determined protein structures and analyzed their spatial
      distribution. In total, 20% of mutations on the surface of known cancer genes
      perturbed protein-protein interactions (PPIs), and this enrichment for PPI
      interfaces was observed for both tumor suppressors (Odds Ratio 1.28, P-value <
      10(-4)) and oncogenes (Odds Ratio 1.17, P-value < 10(-3)). To study this further,
      we constructed a bipartite network representing structurally resolved PPIs from
      all available human complexes in the Protein Data Bank (2,864 proteins, 3,072
      PPIs). Analysis of frequently mutated cancer genes within this network revealed
      that tumor-suppressors, but not oncogenes, are significantly enriched with
      functional mutations in homo-oligomerization regions (Odds Ratio 3.68, P-Value <
      10(-8)). We present two important examples, TP53 and beta-2-microglobulin, for
      which the patterns of somatic mutations at interfaces provide insights into
      specifically perturbed biological circuits. In patients with TP53 mutations,
      patient survival correlated with the specific interactions that were perturbed.
      Moreover, we investigated mutations at the interface of protein-nucleotide
      interactions and observed an unexpected number of missense mutations but not
      silent mutations occurring within DNA and RNA binding sites. Finally, we provide
      a resource of 3,072 PPI interfaces ranked according to their mutation rates.
      Analysis of this list highlights 282 novel candidate cancer genes that encode
      proteins participating in interactions that are perturbed recurrently across
      tumors. In summary, mutation of specific protein interactions is an important
      contributor to tumor heterogeneity and may have important implications for
      clinical outcomes.

PMID- 27043211
TI  - Thrombospondin Type-1 Repeat Domain-Containing Proteins Are Strongly Expressed in
      the Head Region of Hydra.
AB  - The head region of Hydra, the hypostome, is a key body part for developmental
      control and the nervous system. We herein examined genes specifically expressed
      in the head region of Hydra oligactis using suppression subtractive hybridization
      (SSH) cloning. A total of 1414 subtracted clones were sequenced and found to be
      derived from at least 540 different genes by BLASTN analyses. Approximately 25%
      of the subtracted clones had sequences encoding thrombospondin type-1 repeat
      (TSR) domains, and were derived from 17 genes. We identified 11 TSR domain
      containing genes among the top 36 genes that were the most frequently detected in
      our SSH library. Whole-mount in situ hybridization analyses confirmed that at
      least 13 out of 17 TSR domain-containing genes were expressed in the hypostome of
      Hydra oligactis. The prominent expression of TSR domain-containing genes suggests
      that these genes play significant roles in the hypostome of Hydra oligactis. 

PMID- 27043212
TI  - Building a Robust Tumor Profiling Program: Synergy between Next-Generation
      Sequencing and Targeted Single-Gene Testing.
AB  - Next-generation sequencing (NGS) is a powerful platform for identifying cancer
      mutations. Routine clinical adoption of NGS requires optimized quality control
      metrics to ensure accurate results. To assess the robustness of our clinical NGS
      pipeline, we analyzed the results of 304 solid tumor and hematologic malignancy
      specimens tested simultaneously by NGS and one or more targeted single-gene tests
      (EGFR, KRAS, BRAF, NPM1, FLT3, and JAK2). For samples that passed our validated
      tumor percentage and DNA quality and quantity thresholds, there was perfect
      concordance between NGS and targeted single-gene tests with the exception of two
      FLT3 internal tandem duplications that fell below the stringent pre-established
      reporting threshold but were readily detected by manual inspection. In addition,
      NGS identified clinically significant mutations not covered by single-gene tests.
      These findings confirm NGS as a reliable platform for routine clinical use when
      appropriate quality control metrics, such as tumor percentage and DNA quality
      cutoffs, are in place. Based on our findings, we suggest a simple workflow that
      should facilitate adoption of clinical oncologic NGS services at other
      institutions. 

PMID- 27043213
TI  - An approach to (+/-)-Lingzhiol.
AB  - (+/-)-Lingzhiol has been synthesized from commercially available 5,8
      dimethoxytetralone in seven steps with an overall yield of 10.3% via an
      unprecedented acid-catalyzed semipinacol-type rearrangement. In addition, a novel
      strategy for the construction of the tetracyclic 5/5/6/6 core structure of
      lingzhiol has been developed via a tandem rearrangement/reduction/lactonization
      reaction. 

PMID- 27043214
TI  - Accuracy of 4D Flow Measurement of Cerebrospinal Fluid Dynamics in the Cervical
      Spine: An In Vitro Verification Against Numerical Simulation.
AB  - Abnormal alterations in cerebrospinal fluid (CSF) flow are thought to play an
      important role in pathophysiology of various craniospinal disorders such as
      hydrocephalus and Chiari malformation. Three directional phase contrast MRI (4D
      Flow) has been proposed as one method for quantification of the CSF dynamics in
      healthy and disease states, but prior to further implementation of this
      technique, its accuracy in measuring CSF velocity magnitude and distribution must
      be evaluated. In this study, an MR-compatible experimental platform was developed
      based on an anatomically detailed 3D printed model of the cervical subarachnoid
      space and subject specific flow boundary conditions. Accuracy of 4D Flow
      measurements was assessed by comparison of CSF velocities obtained within the in
      vitro model with the numerically predicted velocities calculated from a spatially
      averaged computational fluid dynamics (CFD) model based on the same geometry and
      flow boundary conditions. Good agreement was observed between CFD and 4D Flow in
      terms of spatial distribution and peak magnitude of through-plane velocities with
      an average difference of 7.5 and 10.6% for peak systolic and diastolic
      velocities, respectively. Regression analysis showed lower accuracy of 4D Flow
      measurement at the timeframes corresponding to low CSF flow rate and poor
      correlation between CFD and 4D Flow in-plane velocities.

PMID- 27043215
TI  - Oral physiology, nutrition and quality of life in diabetic patients associated or
      not with hypertension and beta-blockers therapy.
AB  - The relationship between type 2 diabetes oral physiology, nutritional intake and
      quality of life has not been fully elucidated. We assessed the impact of type 2
      diabetes - exclusive or associated with hypertension with beta-blockers treatment
      - on oral physiology, mastication, nutrition and quality of life. This cross
      sectional study was performed with 78 complete dentate subjects (15 natural teeth
      and six masticatory units minimum; without removable or fixed prostheses),
      divided into three groups: diabetics (DM) (n = 20; 45.4 +/- 9.5 years), diabetics
      with hypertension and receiving beta-blockers treatment (DMH) (n = 19; 41.1 +/-
      5.1 years) and controls (n = 39; 44.5 +/- 11.7 years) matched for gender, age and
      socioeconomic status. Blood glucose, masticatory performance, swallowing
      threshold, taste, food intake, stimulated and unstimulated salivary flow, pH and
      buffering capacity of saliva were assessed. Glycemia was higher in DM than in
      controls (P < 0.01). No differences were observed between DM and controls for
      nutrition and quality of life. Both stimulated and unstimulated salivary flow
      rate were lower in DMH (P < 0.01), which also presented the lowest number of
      teeth and masticatory units (P < 0.0001), and reduction in the number of chewing
      cycles (P < 0.01). Controls showed lower Decayed Missing Filled Teeth index
      (DMFT) scores in comparison with DMH (P = 0.021). Masticatory performance and
      saliva buffering capacity were similar among groups. Exclusive type 2 diabetes
      did not alter oral physiology, nutrition or quality of life. However, when
      hypertension and beta-blockers treatment were associated with diabetes, the
      salivary flow rate, chewing cycles and number of teeth decreased. 

PMID- 27043216
TI  - Reaction Mechanism of Guanosine Triphosphate Hydrolysis by the Vision-Related
      Protein Complex Arl3-RP2.
AB  - Complexes of small GTPases with GTPase-activating proteins have been intensively
      studied with the main focus on the complex of H-Ras with p120GAP (Ras-GAP). The
      detailed mechanism of GTP hydrolysis is still unresolved. To clarify it, we
      calculated the energy profile of GTP hydrolysis in the active site of a recently
      characterized vision-related member of this family, the Arl3-RP2 complex. The
      mechanism suggested in this study retains the main features of GTP hydrolysis by
      the Ras-GAP complex, but the relative energies of the corresponding intermediates
      are different and an additional intermediate exists in the Arl3-RP2 complex
      compared with the Ras-GAP. These differences arise from small deviations in the
      catalytic arginine conformation of the active site. In the Arl3-RP2 complex, the
      first two intermediates, corresponding to the Pgamma-Obetagamma bond cleavage and
      the glutamine-assisted proton transfer, are almost isoenergetic with the ES
      complex. Numerical simulations of the kinetic curves demonstrate that the
      concentrations of these intermediates are comparable with that of ES during the
      reaction. The calculated IR spectra reveal specific vibrational bands,
      corresponding to these intermediates. These specific features of the Arl3-RP2
      complex open the opportunity to identify spectroscopically two more reaction
      intermediates in GTP hydrolysis in addition to the ES and EP complexes.

PMID- 27043217
TI  - Laxitextines A and B, Cyathane Xylosides from the Tropical Fungus Laxitextum
      incrustatum.
AB  - Bioassay-guided fractionation of the mycelial extract of a basidiomycete culture
      collected in Kenya led to the isolation of two new cyathane diterpenoids named
      laxitextines A (1) and B (2). The producer strain was characterized by detailed
      taxonomic studies based on rDNA using the 5.8S gene region, the internal
      transcribed spacer 2 (ITS2), and part of the large subunit that identified the
      fungus as Laxitextum incrustatum. The structures of 1 and 2 were elucidated by
      NMR spectroscopic and mass spectrometric analyses. Both compounds exhibited
      moderate activities against Gram-positive bacteria Bacillus subtilis (DSM 10),
      Staphylococcus aureus (DSM 346), and methicillin-resistant Staph. aureus (DSM
      1182). The two compounds also showed variable antiproliferative activities
      against mouse fibroblast (L929) and selected human cell lines (breast cancer MCF
      7, epidermoid carcinoma A431, and umbilical vein endothelial HUVEC). The IC50
      values with respect to the MCF-7 cell line for compounds 1 and 2 were 2.3 and 2.0
      MUM, respectively. 

PMID- 27043218
TI  - Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016:
      treatment of localized high-risk disease.
AB  - PURPOSE: To provide a comprehensive overview and update of the joint consultation
      of the International Consultation on Urological Diseases (ICUD) and Societe
      Internationale d'Urologie for the treatment of localized high-risk upper tract
      urothelial carcinoma (UTUC). METHODS: A detailed analysis of the literature was
      conducted reporting on treatment modalities and outcomes in localized high-risk
      UTUC. An international, multidisciplinary expert committee evaluated and graded
      the data according to the Oxford System of Evidence-based Medicine modified by
      the ICUD. RESULTS: Radical nephroureterectomy (RNU) is the standard of treatment
      for high-grade or clinically infiltrating UTUC and includes the removal of the
      entire kidney, ureter and ipsilateral bladder cuff. The distal ureter can be
      managed either by extravesical or transvesical approach, whereas endoscopically
      assisted procedures are associated with decreased intravesical recurrence-free
      survival. Post-operative intravesical chemotherapy decreases the risk of
      subsequent bladder tumour recurrence. Regional lymph node dissection is of
      prognostic importance in infiltrative UTUC, but its extent has not been
      standardized. Renal-sparing surgery is an option for manageable, high-grade
      tumours of any part of the upper tract, especially of the distal ureter, as an
      alternative to RNU. Endoscopy-based renal-sparing procedures are associated with
      a higher risk of recurrence and progression. CONCLUSIONS: A multimodal approach
      should be considered in localized high-risk UTUC to improve outcomes. RNU is the
      standard of treatment in high-risk disease. Renal-sparing approaches may be
      oncologically equivalent alternatives to RNU in well-selected patients,
      especially in those with distal ureteric tumours.

PMID- 27043219
TI  - Long-term efficacy of implantable cardiac resynchronization therapy plus
      defibrillator for primary prevention of sudden cardiac death in patients with
      mild heart failure: an updated meta-analysis.
AB  - Previous studies of implantable cardiac resynchronization therapy plus
      defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death
      have suggested that CRT-D therapy is less effective in patients with mild heart
      failure and a wide QRS complex. However, the long-term benefits are variable. We
      performed a meta-analysis of randomized trials identified in systematic searches
      of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with
      a mean follow-up of 66 months were included. Overall, CRT-D therapy was
      associated with significantly lower all-cause mortality than was implantable
      cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63-0.96; P = 0.02;
      I (2) = 19 %). However, the risk of cardiac mortality was comparable between two
      groups (OR, 0.74; 95 % CI, 0.53-1.01; P = 0.06). CRT-D treatment was associated
      with a significantly lower risk of hospitalization for heart failure (OR, 0.67;
      95 % CI, 0.50-0.89; P = 0.005; I (2) = 55 %). The composite outcome of all-cause
      mortality and hospitalization for heart failure was also markedly lower with CRT
      D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57-0.77; P <
      0.0001; I (2) = 0 %). CRT-D therapy decreased the long-term risk of mortality and
      heart failure events in patients with mild heart failure with a wide QRS complex.
      However, long-term risk of cardiac mortality was similar between two groups. More
      randomized studies are needed to confirm these findings, especially in patients
      with NYHA class I heart failure or patients without LBBB.

PMID- 27043220
TI  - Electric Field Induced Reversible Phase Transition in Li Doped Phosphorene: Shape
      Memory Effect and Superelasticity.
AB  - Phosphorene, the single-layer form of black phosphorus, as a new member of
      atomically thin material family, has unique puckered atomistic structure and
      remarkable physical and chemical properties. In this paper, we report a discovery
      of an unexpected electromechanical energy conversion phenomenon-shape memory
      effect-in Li doped phosphorene P4Li2, using ab initio density functional theory
      simulations. Two stable phases are found for the two-dimensional (2D) P4Li2
      crystal. Applying an external electric field can turn on or off the unique adatom
      switches in P4Li2 crystals, leading to a reversible structural phase transition
      and thereby the shape memory effect with an tunable strain output as high as
      2.06%. Our results demonstrate that multiple temporary shapes are attainable in
      one piece of P4Li2 material, offering programmability that is particularly useful
      for device designs. Additionally, the P4Li2 displays superelasticity that can
      generate a pseudoelastic tensile strain up to 6.2%. The atomic thickness,
      superior flexibility, excellent electromechanical strain output, the special
      shape memory phenomenon, and the programmability feature endow P4Li2 with great
      application potential in high-efficient energy conversion at nanoscale and
      flexible nanoelectromechanical systems. 

PMID- 27043221
TI  - Nonlinear Surface Dilatational Rheology and Foaming Behavior of Protein and
      Protein Fibrillar Aggregates in the Presence of Natural Surfactant.
AB  - The surface and foaming properties of native soy glycinin (11S) and its heat
      induced fibrillar aggregates, in the presence of natural surfactant steviol
      glycoside (STE), were investigated and compared at pH 7.0 to determine the impact
      of protein structure modification on protein-surfactant interfacial interactions.
      The adsorption at, and nonlinear dilatational rheological behavior of, the air
      water interface were studied by combining drop shape analysis tensiometry,
      ellipsometry, and large-amplitude oscillatory dilatational rheology. Lissajous
      plots of surface pressure versus deformation were used to analyze the surface
      rheological response in terms of interfacial microstructure. The heat treatment
      generates a mixture of long fibrils and unconverted peptides. The presence of
      small peptides in 11S fibril samples resulted in a faster adsorption kinetics
      than that of native 11S. The addition of STE affected the adsorption of 11S
      significantly, whereas no apparent effect on the adsorption of the 11S fibril
      peptide system was observed. The rheological response of interfaces stabilized by
      11S-STE mixtures also differed significantly from the response for 11S fibril
      peptide-STE mixtures. For 11S, the STE reduces the degree of strain hardening in
      extension and increases strain hardening in compression, suggesting the
      interfacial structure may change from a surface gel to a mixed phase of protein
      patches and STE domains. The foams generated from the mixtures displayed
      comparable foam stability to that of pure 11S. For 11S fibril-peptide mixtures
      STE only significantly affects the response in extension, where the degree of
      strain softening is decreased compared to the pure fibril-peptide system. The
      foam stability of the fibril-peptide system was significantly reduced by STE.
      These findings indicate that fibrillization of globular proteins could be a
      potential strategy to modify the complex surface and foaming behaviors of protein
      surfactant mixtures. 

PMID- 27043222
TI  - Heterogeneous Catalysis: Understanding for Designing, and Designing for
      Applications.
AB  - "... Despite the introduction of high-throughput and combinatorial methods that
      certainly can be useful in the process of catalysts optimization, it is
      recognized that the generation of fundamental knowledge at the molecular level is
      key for the development of new concepts and for reaching the final objective of
      solid catalysts by design ..." Read more in the Editorial by Avelino Corma.

PMID- 27043223
TI  - [(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in
      Rats.
AB  - PURPOSE: Epileptogenesis, i.e., development of epilepsy, involves a number of
      processes that alter the brain function in the way that triggers spontaneous
      seizures. Kindling is one of the most used animal models of temporal lobe
      epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high
      inter-assay success unpredictability. This study was aimed to analyze the
      eventual regional brain metabolic changes during epileptogenesis in the
      pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling
      outcome parameter. PROCEDURES: In vivo longitudinal positron emission tomography
      (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ
      kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male
      rats were performed in order to evaluate the regional brain metabolism. RESULTS:
      The half of the PTZ-injected rats reached the kindled state. In addition, a
      significant decrease of [(18)F]FDG uptake at the end of the protocol in most of
      the brain structures of kindled animals was found, reflecting the characteristic
      epilepsy-associated hypometabolism. However, PTZ-injected animals but not
      reaching the kindled state did not show this widespread brain hypometabolism.
      Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake
      normalized to pons turned out to be a predictive index of the kindling outcome.
      Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in
      positively kindled rats compared to non-kindled ones just after the fifth PTZ
      session. CONCLUSION: Non-invasive PET neuroimaging was a useful tool for
      discerning epileptogenesis progression in this animal model. Particularly, the
      [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter
      to differentiate resistant and non-resistant animals to the PTZ kindling.

PMID- 27043224
TI  - Glycemic excursions are positively associated with HbA1c reduction from baseline
      after treatment with acarbose in patients with type 2 diabetes on metformin
      monotherapy.
AB  - BACKGROUND: The aim of the present study was to examine the association between
      glycemic excursions before treatment and HbA1c reduction after treatment
      intensification with acarbose or glibenclamide in patients with type 2 diabetes
      (T2D). METHODS: Patients receiving single or dual oral antidiabetic drug
      treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin
      monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either
      acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for
      16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic
      excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment
      efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline
      HbA1c - post-treatment HbA1c)/baseline HbA1c * 100. RESULTS: Fifty patients (mean
      [+/-SD] age 53.5 +/- 8.2 years, 48 % men, mean baseline HbA1c 8.4 +/- 1.2 %) were
      analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction
      from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not
      glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that
      the association between baseline MAGE and relative HbA1c reduction from baseline
      (beta = 0.125, P = 0.029) in patients treated with acarbose remained significant
      after adjustment for several confounders (P < 0.05 for all models). CONCLUSIONS:
      In patients with T2D on metformin monotherapy, baseline MAGE was positively
      correlated with relative HbA1c reduction from baseline after treatment with
      acarbose, but not glibenclamide. These findings highlight the importance of
      glycemic excursions in individualized treatment for patients with T2D.

PMID- 27043225
TI  - Multiclass Carcinogenic DNA Adduct Quantification in Formalin-Fixed Paraffin
      Embedded Tissues by Ultraperformance Liquid Chromatography-Tandem Mass
      Spectrometry.
AB  - DNA adducts are a measure of internal exposure to genotoxicants and an important
      biomarker for human risk assessment. However, the employment of DNA adducts as
      biomarkers in human studies is often restricted because fresh-frozen tissues are
      not available. In contrast, formalin-fixed paraffin-embedded (FFPE) tissues with
      clinical diagnosis are readily accessible. Recently, our laboratory reported that
      DNA adducts of aristolochic acid, a carcinogenic component of Aristolochia herbs
      used in traditional Chinese medicines worldwide, can be recovered quantitatively
      from FFPE tissues. In this study, we have evaluated the efficacy of our method
      for retrieval of DNA adducts from archived tissue by measuring DNA adducts
      derived from four other classes of human carcinogens: polycyclic aromatic
      hydrocarbons (PAHs), aromatic amines, heterocyclic aromatic amines (HAAs), and N
      nitroso compounds (NOCs). Deoxyguanosine (dG) adducts of the PAH benzo[a]pyrene
      (B[a]P), 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (dG-N(2)-B[a]PDE); the aromatic amine 4-aminobiphenyl (4
      ABP), N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP); the HAA 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-(deoxyguanosin-8-yl)-PhIP (dG-C8
      PhIP); and the dG adducts of the NOC 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK), O(6)-methyl-dG (O(6)-Me-dG) and O(6)-pyridyloxobutyl-dG (O(6)-POB
      dG), formed in liver, lung, bladder, pancreas, or colon were recovered in
      comparable yields from fresh-frozen and FFPE preserved tissues of rodents treated
      with the procarcinogens. Quantification was achieved by ultraperformance liquid
      chromatography coupled with electrospray ionization ion-trap multistage mass
      spectrometry (UPLC/ESI-IT-MS(3)). These advancements in the technology of DNA
      adduct retrieval from FFPE tissue clear the way for use of archived pathology
      samples in molecular epidemiology studies designed to assess the causal role of
      exposure to hazardous chemicals with cancer risk.

PMID- 27043226
TI  - A new sesquiterpene from the gorgonian coral Menella sp.
AB  - A new sesquiterpene named menecubebane B (1) and a known analogue (2) were
      isolated from the gorgonian coral Menella sp. Their structures were elucidated by
      the extensive analyses of spectroscopic data and by the comparison with related
      literature. Cytotoxic effect against both Eca9706 and HeLa cell lines was
      evaluated, revealing 1 exhibited moderate cytotoxicity against the two cell lines
      involved with IC50 values being 20.8 and 30.6 MUM, respectively. 

PMID- 27043227
TI  - An infant with ash-leaf and cafe au lait spots: a case of double phakomatosis.

PMID- 27043228
TI  - Comparison of the therapeutic effects of total laryngectomy and a larynx
      preservation approach in patients with T4a laryngeal cancer and thyroid cartilage
      invasion: A multicenter retrospective review.
AB  - BACKGROUND: In T4a laryngeal cancer with thyroid cartilage invasion, no optimal
      frontline treatment has yet been defined in controlled trials. METHODS: We
      reviewed data from 89 patients with T4a laryngeal cancer featuring thyroid
      cartilage invasion who were treated initially with either total laryngectomy (n =
      53) or a larynx-preservation strategy (n = 36). RESULTS: The median progression
      free survival (PFS) of the total laryngectomy group had not been attained at the
      time of analysis and was thus significantly longer than that of the larynx
      preservation group (8.7 months). The median overall survival (OS) of patients who
      underwent total laryngectomy was 87.2 months, significantly longer than that of
      the larynx-preservation group (31.3 months). The survival benefit of primary
      surgery compared to a larynx-preservation strategy was more striking in patients
      of lower N classifications. CONCLUSION: Total laryngectomy may be a better
      therapeutic option to treat T4a laryngeal cancer featuring thyroid cartilage
      invasion, especially in patients exhibiting limited nodal involvement (N0/N1).
      (c) 2016 Wiley Periodicals, Inc. Head Neck, 2016 (c) 2016 Wiley Periodicals, Inc.
      Head Neck 38:1271-1277, 2016.

PMID- 27043229
TI  - Structures and Electronic Properties of TinV (n = 1-16) Clusters: First
      Principles Calculations.
AB  - Structures and electronic properties of TinV (n = 1-16) clusters have been
      investigated using density functional theory with the generalized gradient
      approximatio. The calculations have shown that the TinV clusters favor compact
      spherical structures having similar conformations to the pure Tin clusters. The
      results show that the vanadium atom remains on the surface when n ? 8 and n = 16,
      while for n = 9-15, it occupies the endohedral position. The Ti6V, Ti12V, and
      Ti14V clusters are found to be more stable than their neighbors, consistent with
      pure Tin clusters that have the same size. Additionally Ti4V has been found to be
      also magic, consistent with recent reports of B- and Al-doped Ti clusters. Small
      TinV (n ? 4) clusters exhibit a transition from metallic-like to semimetallic
      electronic structure, while for n = 5 onward, no significant changes are observed
      compared with pure Tin clusters. 

PMID- 27043230
TI  - Caught red-handed.

PMID- 27043231
TI  - Validity of the Brazilian version of the Venham's behavior rating scale.
AB  - BACKGROUND: Venham's Behavior Rating Scale (VBRS) is a measure of uncooperative
      behavior developed to assess children's responses to dental stress. AIM: To
      evaluate the validity of the Brazilian version of the VBRS. DESIGN: Children aged
      7-13 years were invited to participate in this study. Child behavior was
      concurrently assessed with both the VBRS and the Frankl Scale. A receiver
      operating characteristic curve (ROC) was plotted to determine the cut-off points
      of the Brazilian version of the VBRS. Criterion validity was determined using
      Spearman's correlation coefficient. Discriminant validity was tested before and
      after scale dichotomization. RESULTS: A total of 265 children participated in
      this study. According to the ROC curve, the >=1 cut-off point was best for this
      population (SENS 97.4%; SPEC 94.7%). The Brazilian version of the VBRS was
      significantly correlated with the Frankl Scale (r -0.69; <0.001, r -0.72;
      <0.001). Child behavior assessed was related to complexity of treatment, type of
      procedure, use of local anesthesia, and dental fear. CONCLUSIONS: The results
      provide strong evidence for the validity of Brazilian version of the VBRS in
      behavior assessment of children aged 7-13 years during dental care.

PMID- 27043232
TI  - Drugs, games, and devices for enhancing cognition: implications for work and
      society.
AB  - As work environments change, the demands on working people change. Cognitive
      abilities in particular are becoming progressively more important for work
      performance and successful competition in a global environment. However, work
      related stress, performance over long hours, lack of sleep, shift work, and jet
      lag affect cognitive functions. Therefore, an increasing number of healthy people
      are reported to use cognitive-enhancing drugs, as well as other interventions,
      such as noninvasive brain stimulation, to maintain or improve work performance.
      This review summarizes research on pharmacological and technical methods as well
      as cognitive training, including game apps for the brain, in healthy people. In
      neuropsychiatric disorders, impairments in cognitive functions can drastically
      reduce the chances of returning to work; therefore, this review also summarizes
      findings from pharmacological and cognitive-training studies in neuropsychiatric
      disorders.

PMID- 27043233
TI  - Hematologic malignancies: newer strategies to counter the BCL-2 protein.
AB  - INTRODUCTION: BCL-2 is the founding member of the BCL-2 family of apoptosis
      regulatory proteins that either induce (pro-apoptotic) or inhibit (anti
      apoptotic) apoptosis. The anti-apoptotic BCL-2 is classified as an oncogene, as
      damage to the BCL-2 gene has been shown to cause a number of cancers, including
      lymphoma. Ongoing research has demonstrated that disruption of BCL-2 leads to
      cell death. BCL-2 is also known to be involved in the development of resistance
      to chemotherapeutic agents, further underscoring the importance of targeting the
      BCL-2 gene in cancer therapeutics. Thus, numerous approaches have been developed
      to block or modulate the production of BCL-2 at the RNA level using antisense
      oligonucleotides or at the protein level with BCL-2 inhibitors, such as the novel
      ABT737. METHODS: In this article, we briefly review previous strategies to target
      the BCL-2 gene and focus on a new approach to silence DNA, DNA interference
      (DNAi). RESULTS AND CONCLUSION: DNA interference is aimed at blocking BCL-2 gene
      transcription. Evaluations of this technology in preclinical and early clinical
      studies are very encouraging and strongly support further development of DNAi as
      cancer therapeutics. A pilot phase II clinical trial in patients with relapsed or
      refractory non-Hodgkin lymphoma, PNT2258 demonstrated clinical benefit in 11 of
      13 patients with notable responses in diffuse large B cell lymphoma and
      follicular lymphoma. By targeting the DNA directly, the DNAi technology promises
      to be more effective compared with other gene-interference strategies that target
      the RNA or protein but leaves the dysregulated DNA functional.

PMID- 27043234
TI  - Focus on antimicrobial use in the era of increasing antimicrobial resistance in
      ICU.

PMID- 27043235
TI  - Research in Latin America: opportunities and challenges.

PMID- 27043236
TI  - Aspirin may improve outcome in sepsis by augmentation of the inflammatory
      response.

PMID- 27043238
TI  - The joint cardiovascular research profile of the university medical centres in
      the Netherlands.
AB  - Biomedical scientific research in the Netherlands has a good reputation
      worldwide. Quantitatively, the university medical centres (UMCs) deliver about 40
      % of the total number of scientific publications of this research. Analysis of
      the bibliometric output data of the UMCs shows that their research is highly
      cited. These output-based analyses also indicate the high impact of
      cardiovascular scientific research in these centres, illustrating the strength of
      this research in the Netherlands. A set of six joint national cardiovascular
      research topics selected by the UMCs can be recognised. At the top are heart
      failure, rhythm disorder research and atherosclerosis. National collaboration of
      top scientists in consortia in these three areas is successful in acquiring
      funding of large-scale programs. Our observations suggest that funding national
      consortia of experts focused on a few selected research topics may increase the
      international competitiveness of cardiovascular research in the Netherlands. 

PMID- 27043237
TI  - Effect of probiotics on the incidence of ventilator-associated pneumonia in
      critically ill patients: a randomized controlled multicenter trial.
AB  - PURPOSE: To evaluate the potential preventive effect of probiotics on ventilator
      associated pneumonia (VAP). METHODS: This was an open-label, randomized,
      controlled multicenter trial involving 235 critically ill adult patients who were
      expected to receive mechanical ventilation for >=48 h. The patients were
      randomized to receive (1) a probiotics capsule containing live Bacillus subtilis
      and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a
      nasogastric feeding tube plus standard preventive strategies or (2) standard
      preventive strategies alone, for a maximum of 14 days. The development of VAP was
      evaluated daily, and throat swabs and gastric aspirate were cultured at baseline
      and once or twice weekly thereafter. RESULTS: The incidence of microbiologically
      confirmed VAP in the probiotics group was significantly lower than that in the
      control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to
      develop VAP was significantly longer in the probiotics group than in the control
      group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients
      with acquisition of gastric colonization of potentially pathogenic microorganisms
      (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P
      = 0.004). However, the proportion of patients with eradication PPMO colonization
      on both sites of the oropharynx and stomach were not significantly different
      between the two groups. The administration of probiotics did not result in any
      improvement in the incidence of clinically suspected VAP, antimicrobial
      consumption, duration of mechanical ventilation, mortality and length of hospital
      stay. CONCLUSION: Therapy with the probiotic bacteria B. Subtilis and E. faecalis
      are an effective and safe means for preventing VAP and the acquisition of PPMO
      colonization in the stomach.

PMID- 27043239
TI  - Toll-Like Receptors in Cystic Fibrosis: Impact of Dysfunctional microRNA on
      Innate Immune Responses in the Cystic Fibrosis Lung.
AB  - Toll-like receptors (TLRs) are a class of pattern recognition receptors that are
      particularly expressed in the sentinel and epithelial cells in the body,
      including the lung. They are central players in the innate immune system in
      response to microbial infection, and are the triggers of a complex pathway
      network that both promotes the inflammatory response and influences the adaptive
      immune response. These pathways are transiently and finely tuned by cellular
      factors, including a cell's microRNA response program. MicroRNAs are small, non
      coding RNAs that specifically regulate gene expression. In this article, we
      review the disease-specific microRNA regulatory network of cystic fibrosis, a
      debilitating and ultimately fatal disease and, specifically, its effect on TLR
      signalling.

PMID- 27043240
TI  - Well-Being Therapy: Current Indications and Emerging Perspectives.

PMID- 27043241
TI  - Treatment of CMV infection after allogeneic hematopoietic stem cell
      transplantation.
AB  - Despite a remarkable reduction in the past decades, cytomegalovirus (CMV) disease
      in allogeneic hematopoietic stem cell transplant (HSCT) recipients remains a
      feared complication, still associated with significant morbidity and mortality.
      Today, first line treatment of CMV infection/reactivation is still based on dated
      antiviral compounds Ganciclovir (GCV), Foscarnet (FOS) and Cidofovir (CDF) with
      their burdensome weight of side effects. Maribavir (MBV), Letermovir (LMV) and
      Brincidofovir (BDF) are three new promising anti-CMV drugs without
      myelosuppressive properties or renal toxic effects that are under investigation
      in randomized phase II and III trials. Adoptive T-cell therapy (ATCT) in CMV
      infection possesses a strong rationale, demonstrated by several proof of concept
      studies; its feasibility is currently under investigation by clinical trials.
      ATCT from third-party and naive donors could meet the needs of HSCT recipients of
      seronegative donors and cord blood grafts. In selected patients such as
      recipients of T-cell depleted grafts, ATCT, based on CMV-specific host T-cells
      reconstitution kinetics, would be of value in the prophylactic and/or preemptive
      CMV treatment. Vaccine-immunotherapy has the difficult task to reduce the
      incidence of CMV reactivation/infection in highly immunocompromised HSCT
      patients. Newer notions on CMV biology may represent the base to flush out the
      Troll of transplantation. 

PMID- 27043242
TI  - Economic evaluation of fecal microbiota transplantation for the treatment of
      recurrent Clostridium difficile infection in Australia.
AB  - BACKGROUND AND AIM: Clostridium difficile is the most common cause of hospital
      acquired diarrhea in Australia. In 2013, a randomized controlled trial
      demonstrated the effectiveness of fecal microbiota transplantation (FMT) for the
      treatment of recurrent Clostridium difficile infection (CDI). The aim of this
      study is to evaluate the cost-effectiveness of fecal microbiota transplantation
      via either nasoduodenal or colorectal delivery-compared with vancomycin for the
      treatment of recurrent CDI in Australia. METHODS: A Markov model was developed to
      compare the cost-effectiveness of fecal microbiota transplantation compared with
      standard antibiotic therapy. A literature review of clinical evidence informed
      the structure of the model and the choice of parameter values. Clinical
      effectiveness was measured in terms of quality-adjusted life years. Uncertainty
      in the model was explored using probabilistic sensitivity analysis. RESULTS: Both
      nasoduodenal and colorectal FMT resulted in improved quality of life and reduced
      cost compared with vancomycin. The incremental effectiveness of either FMT
      delivery compared with vancomycin was 1.2 (95% CI: 0.1, 2.3) quality-adjusted
      life years, or 1.4 (95% CI: 0.4, 2.4) life years saved. Treatment with vancomycin
      resulted in an increased cost of AU$4094 (95% CI: AU$26, AU$8161) compared with
      nasoduodenal delivery of FMT and AU$4045 (95% CI: -AU$33, AU$8124) compared with
      colorectal delivery. The mean difference in cost between colorectal and
      nasoduodenal FMT was not significant. CONCLUSIONS: If FMT, rather than
      vancomycin, became standard care for recurrent CDI in Australia, the estimated
      national healthcare savings would be over AU$4000 per treated person, with a
      substantial increase in quality of life.

PMID- 27043243
TI  - Numerically simulated exposure of children and adults to pulsed gradient fields
      in MRI.
AB  - PURPOSE: To determine exposure to gradient switching fields of adults and
      children in a magnetic resonance imaging (MRI) scanner by evaluating internal
      electric fields within realistic models of adult male, adult female, and child
      inside transverse and longitudinal gradient coils, and to compare these results
      with compliance guidelines. MATERIALS AND METHODS: Patients inside x-, y-, and z
      gradient coils were simulated using anatomically realistic models of adult male,
      adult female, and child. The induced electric fields were computed for 1 kHz
      sinusoidal current with a magnitude of 1 A in the gradient coils. Rheobase
      electric fields were then calculated and compared to the International Commission
      on Non-Ionizing Radiation Protection (ICNIRP) 2004 and International
      Electrotechnical Commission (IEC) 2010 guidelines. The effect of the human body,
      coil type, and skin conductivity on the induced electric field was also
      investigated. RESULTS: The internal electric fields are within the first level
      controlled operating mode of the guidelines and range from 2.7V m-1 to 4.5V m-1 ,
      except for the adult male inside the y-gradient coil (induced field reaches 5.4V
      m-1 ).The induced electric field is sensitive to the coil type (electric field in
      the skin of adult male: 4V m-1 , 4.6V m-1 , and 3.8V m-1 for x-, y-, and z
      gradient coils, respectively), the human body model (electric field in the skin
      inside y-gradient coil: 4.6V m-1 , 4.2V m-1 , and 3V m-1 for adult male, adult
      female, and child, respectively), and the skin conductivity (electric field 2.35
      4.29% higher for 0.1S m-1 skin conductivity compared to 0.2S m-1 ). CONCLUSION:
      The y-gradient coil induced the largest fields in the patients. The highest
      levels of internal electric fields occurred for the adult male model. J. Magn.
      Reson. Imaging 2016;44:1360-1367.

PMID- 27043244
TI  - An alternative parameter for early forecasting clinical response in NSCLC
      patients during radiotherapy: proof of concept study.
AB  - OBJECTIVE: Positron emission tomography with (18)F fludeoxyglucose integrated
      with CT ((18)F-FDG PET/CT) is a recommended imaging procedure in the evaluation
      of non-small-cell lung cancers (NSCLCs). Radiochemotherapy (RCT) is a mainstay
      for treatment of locally advanced NSCLC, for which overall survival still remains
      poor. Early evaluation of treatment response may help in decision-making to
      complete radiotherapy (RT) or to switch to other treatment modalities. The
      present study aimed to evaluate the performance of new metabolic parameters based
      on a simplified kinetic analysis on a single time point (SKA-S)-derived
      mathematical method, as compared with standardized uptake value (SUV) measurement
      during RT. METHODS: Four patients treated with RT or RCT for NSCLC were evaluated
      using (18)F-FDG PET/CT during RT and after treatment completion. Whole-body (18)F
      FDG PET/CT was performed followed by four additional list-mode acquisitions
      centered over the target lesion. Response was evaluated at four times (i.e. PET1
      PET4) by calculating standard SUV values and T80%, the time taken to reach 80% of
      (18)F-FDG metabolized fraction using a SKA-S-derived mathematical method.
      RESULTS: Data from SUV and T80% calculations were found to be controversial. T80%
      was found to be more predictive of clinical outcome. CONCLUSION: Although results
      from this pilot study should be further confirmed in a large prospective study,
      the data suggest that T80% is a promising metabolic biomarker for assessing early
      response to RT. ADVANCES IN KNOWLEDGE: In this proof of concept study, we show
      that T80% defined from a mathematic model taking into account the net influx rate
      constant and vascular volume could be consider as a promising biomarker as
      compared with the maximum SUV.

PMID- 27043245
TI  - Evaluation of the simultaneous removal of recalcitrant drugs (bezafibrate,
      gemfibrozil, indomethacin and sulfamethoxazole) and biodegradable organic matter
      from synthetic wastewater by electro-oxidation coupled with a biological system.
AB  - Pharmaceutical degradation in conventional wastewater treatment plants (WWTP)
      represents a challenge since municipal wastewater and hospital effluents contain
      pharmaceuticals in low concentrations (recalcitrant and persistent in WWTP) and
      biodegradable organic matter (BOM) is the main pollutant. This work shows the
      feasibility of coupling electro-oxidation with a biological system for the
      simultaneous removal of recalcitrant drugs (bezafibrate, gemfibrozil,
      indomethacin and sulfamethoxazole (BGIS)) and BOM from wastewater. High removal
      efficiencies were attained without affecting the performance of activated sludge.
      BGIS degradation was performed by advanced electrochemical oxidation and the
      activated sludge process for BOM degradation in a continuous reactor. The
      selected electrochemical parameters from microelectrolysis tests (1.2 L s(-1) and
      1.56 mA cm(-2)) were maintained to operate a filter press laboratory reactor FM01
      LC using boron-doped diamond as the anode. The low current density was chosen in
      order to remove drugs without decreasing BOM and chlorine concentration control,
      so as to avoid bulking formation in the biological process. The wastewater
      previously treated by FM01-LC was fed directly (without chemical modification) to
      the activated sludge reactor to remove 100% of BGIS and 83% of BOM; conversely,
      the BGIS contained in wastewater without electrochemical pre-treatment were
      persistent in the biological process and promoted bulking formation. 

PMID- 27043246
TI  - Inhibition of Histone Deacetylases Enhances the Osteogenic Differentiation of
      Human Periodontal Ligament Cells.
AB  - One of the characteristics of periodontal ligament (PDL) cells is their
      plasticity. Yet, the underlying mechanisms responsible for this phenomenon are
      unknown. One possible mechanism might be related to epigenetics, since histone
      deacetylases (HDACs) have been shown to play a role in osteoblast
      differentiation. This study was aimed to investigate the role of HDACs in
      osteogenic differentiation of human PDL (hPDL) cells. HDAC inhibitor trichostatin
      A (TSA) had no effect on cell viability as was assessed by MTT assay. Osteogenic
      and adipogenic differentiation was analyzed by gene expression, ALP activity and
      mineral deposition. Western blotting was used to investigate the effect of TSA on
      histone acetylation and protein expression. In the presence of the HDAC inhibitor
      osteogenic differentiation was induced; osteoblast-related gene expression was
      increased significantly. ALP activity and mineral nodule formation were also
      enhanced. Inhibition of HDACs did not induce differentiation into the adipocyte
      lineage. hPDL highly expressed HDACs of both class I (HDAC 1, 2, 3) and class II
      (HDAC 4, 6). During osteogenic differentiation HDAC 3 expression gradually
      decreased. This was apparent in the absence and presence of the inhibitor. The
      level of acetylated Histone H3 was increased during osteogenic differentiation.
      Inhibition of HDAC activity induced hyperacetylation of Histone H3, therefore,
      demonstrating Histone H3 as a candidate target molecule for HDAC inhibition. In
      conclusion, hPDL cells express a distinguished series of HDACs and these enzymes
      appear to be involved in osteogenic differentiation. This finding suggests a
      potential application of TSA for bone regeneration therapy by hPDL cells.

PMID- 27043247
TI  - Dysregulation of Norepinephrine Release in the Absence of Functional
      Synaptotagmin 7.
AB  - Synaptotagmin 7 (Syt7) is expressed in cardiac sympathetic nerve terminals where
      norepinephrine (NE) is released in both Ca(2+)-dependent exocytosis and Ca(2+)
      independent norepinephrine transporter (NET)-mediated overflow. The role of Syt7
      in the regulation of NE release from cardiac sympathetic nerve terminals is
      tested by employing a Syt7 knock-in mouse line that expresses a non-functional
      mutant form of Syt7. In cardiac sympathetic nerve terminals prepared from these
      Syt7 knock-in mice, the Ca(2+)-dependent component of NE release was diminished.
      However, these terminals displayed upregulated function of NET (~130% of
      controls) and a significant increase in Ca(2+)-independent NE overflow (~140% of
      controls), which is greater than the Ca(2+)-dependent component of NE exocytosis
      occurring in wild-type controls. Consistent with a significant increase in NE
      overflow, the Syt7 knock-in mice showed significantly higher blood pressures
      compared to those of littermate wild-type and heterozygous mice. Our results
      indicate that the lack of functional Syt7 dysregulates NE release from cardiac
      sympathetic nerve terminals.

PMID- 27043248
TI  - Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by
      Increased Levels of SQSTM1/p62 Protein.
AB  - Vacuolar proton pump H(+)-adenosine triphosphatases (V-ATPases) play an important
      role in osteoclast function. Further understanding of the cellular and molecular
      mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive
      drugs specifically targeting osteoclast V-ATPases. In this study, we observed
      that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the
      protein level of SQSTM1/p62, a known negative regulator of osteoclast formation.
      Consistently, we found that bafilomycin A1 diminishes the intracellular
      accumulation of the acidotropic probe lysotracker in osteoclast-like cells;
      indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast
      formation with attenuation of cell fusion and multi-nucleation of osteoclast-like
      cells during osteoclast differentiation. Taken together, these data indicate that
      bafilomycin A1 attenuates osteoclast differentiation in part via increased levels
      of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V
      ATPase inhibition in osteoclasts.

PMID- 27043250
TI  - Oral exposure to immunostimulating drugs results in early changes in innate
      immune parameters in the spleen.
AB  - The development of immune-dependent drug hypersensitivity reactions (IDHR) is
      likely to involve activation of the innate immune system to stimulate neo-antigen
      specific T-cells. Previously it has been shown that, upon oral exposure to
      several drugs with immune-adjuvant capacity, mice developed T-cell-dependent
      responses to TNP-OVA. These results were indicative of the adjuvant potential of
      these drugs. The present study set out to evaluate the nature of this adjuvant
      potential by focusing on early immune changes in the spleen, by testing several
      drugs in the same experimental model. Mice were exposed to one or multiple oral
      doses of previously-tested drugs: the non-steroidal-anti-inflammatory drug
      (NSAID) diclofenac (DF), the analgesic acetaminophen (APAP), the anti-epileptic
      drug carbamazepine (CMZ) or the antibiotic ofloxacin (OFLX). Within 24 h after
      the final dosing, early innate and also adaptive immune parameters in the spleen
      were examined. In addition, liver tissue was also evaluated for damage. Exposure
      to APAP resulted in severe liver damage, increased levels of serum alanine
      aminotransferase (ALT) and local MIP-2 expression. DF exposure did not cause
      visible liver damage, but did increase liver weight. DF also elicited clear
      effects on splenic innate and adaptive immune cells, i.e. increased levels of NK
      cells and memory T-cells. Furthermore, an increase in plasma MIP-2 levels
      combined with an influx of neutrophils into the spleen was observed. OFLX and CMZ
      exposure resulted in increased liver weights, MIP-2 expression and up-regulation
      of co-stimulatory molecules on antigen-presenting cells (APC). The data suggested
      that multiple immune parameters were altered upon exposure to drugs known to
      elicit immunosensitization and that broad evaluation of immune changes in
      straightforward short-term animal models is needed to determine whether a drug
      may harbor the hazard to induce IDHR. The oral exposure approach as used here may
      be applied in the future as an immunotoxicological research tool in this type of
      evaluation.

PMID- 27043251
TI  - Dual leucine zipper kinase (MAP3K12) modulators: a patent review (2010-2015).
AB  - INTRODUCTION: The dual leucine zipper kinase (DLK, MAP3K12) is essential for
      neuronal development and has been shown to mediate axon regeneration. On the
      other hand, DLK is involved in the pathogenesis of neurodegenerative disease and
      diabetes mellitus. Several patents have been published claiming to modulate or
      inhibit DLK by various approaches including ATP competitive inhibitors. In
      addition, two publications describe SAR of highly selective DLK inhibitors with
      efficacy in distinct mouse models of neurodegeneration. AREAS COVERED: This
      review summarized patents claiming to modulate DLK activity published between
      2010 and 2015. Peer-reviewed publications related to the patents and additional
      peer-reviewed publications are included. This article describes 18 patents from
      three pharmaceutical companies and three academic research groups. EXPERT
      OPINION: Several methods are proposed to modulate DLK activity, some of them very
      experimental and not suitable for easy application in patients. ATP competitive
      kinase inhibitors exert high affinity, but for the majority, no information about
      their selectivity is available. To date, two inhibitors have been tested in mice.
      Given the controversial findings that DLK is required for neurodegeneration and
      for axon regeneration, more research is needed to further elucidate the
      regulation and the function of this kinase in diverse organs/tissues and under
      physiological and pathological conditions.

PMID- 27043252
TI  - On the overlap between bilingual language control and domain-general executive
      control.
AB  - We explored the overlap between bilingual language control (bLC) and domain
      general executive control (EC) by focusing on inhibitory control processes. We
      tested 62 bilinguals in linguistic and non-linguistic switching tasks for two
      types of costs, such as the n-1 shift cost and the n-2 repetition cost. In order
      to explore the involvement of inhibitory control in bLC and EC, we assessed the
      pattern of switch costs in the two tasks and then we correlated them between
      tasks. Results showed reduced n-2 repetition costs as compared to n-1 shift costs
      in the linguistic task only, suggesting that small amount of inhibition were
      deployed when switching between languages. Importantly, neither the n-1 shift
      costs nor the n-2 repetition costs were correlated between tasks. These results,
      supported by additional evidence from the ex-Gaussian analysis, suggest that
      inhibitory control is differently involved in bLC and in EC. 

PMID- 27043253
TI  - Errors in visuo-haptic and haptic-haptic location matching are stable over long
      periods of time.
AB  - People make systematic errors when they move their unseen dominant hand to a
      visual target (visuo-haptic matching) or to their other unseen hand (haptic
      haptic matching). Why they make such errors is still unknown. A key question in
      determining the reason is to what extent individual participants' errors are
      stable over time. To examine this, we developed a method to quantify the
      consistency. With this method, we studied the stability of systematic matching
      errors across time intervals of at least a month. Within this time period,
      individual subjects' matches were as consistent as one could expect on the basis
      of the variability in the individual participants' performance within each
      session. Thus individual participants make quite different systematic errors, but
      in similar circumstances they make the same errors across long periods of time. 

PMID- 27043254
TI  - Involuntary symbol manipulation (Pig Latin) from external control: Implications
      for thought suppression.
AB  - In ironic processing, one is more likely to think about something (e.g., white
      bears) when instructed to not think about that thing. Entry into consciousness of
      such content may be automatic, reflecting the 'encapsulated' nature of the
      generation of conscious contents. Based on this research, the Reflexive Imagery
      Task (RIT) reveals that, following the activation of action sets, conscious
      contents can arise involuntarily and systematically in response to external
      stimuli. In the most basic version of this paradigm, participants are presented
      with visual objects and instructed to not think of the names of the objects,
      which is challenging. Here, we addressed one criticism of the RIT-that the effect
      arises only for automatic processes (e.g., forms of cued-memory retrieval) and
      not for more complex processes (e.g., symbol manipulation). Participants were
      first trained to perform a word-manipulation task similar to the game of Pig
      Latin (e.g., "CAR" becomes "AR-CAY"). Such a task involves complex symbol
      manipulations that are associated with processes in frontal cortex. After
      training, participants were instructed to not transform stimulus words in this
      way. The RIT effect still arose under these conditions. This striking finding is
      relevant to theories of cognitive control, psychopathology, and
      conscious/unconscious processing. 

PMID- 27043255
TI  - Embodiment of abstract categories in space... grounding or mere compatibility
      effects? The case of politics.
AB  - In two experiments, the role played by stimulus response compatibility in driving
      the spatial grounding of abstract concepts is examined. In Experiment 1,
      participants were asked to classify politics-related words appearing to the left
      or the right side of a computer monitor as socialist or conservative. Responses
      were given by pressing vertically aligned keys and thus orthogonal to the spatial
      information that may have been implied by the words. Responses given by left or
      right index finger were counterbalanced. In Experiment 2, a lexical decision
      task, participants categorized political words or non-words presented to the left
      or the right auditory channels, by pressing the top/bottom button of a response
      box. The response category labels (word or non-word) were also orthogonal to the
      spatial information that may have been implied by the stimulus words. In both
      experiments, responses were faster when socialism-related words were presented on
      the left and conservatism-related words were presented on the right, irrespective
      of the reference of the response keys or labels. Overall, our findings suggest
      that the spatial grounding of abstract concepts (or at least politics-related
      ones) is independent of experimentally driven stimulus-response compatibility
      effects. 

PMID- 27043256
TI  - Allergic Rhinitis Is Associated With Periodontitis: A Population-Based Study.
AB  - BACKGROUND: Little is known regarding associations of periodontitis with diseases
      of the nose, one of the structures adjacent to the mouth. This study aims to
      explore the association between periodontitis and previous allergic rhinitis (AR)
      using a matched patient-control study design from a population-based dataset in
      Taiwan. METHODS: Data were sourced from the Longitudinal Health Insurance
      Database 2000 for 71,182 patients with chronic periodontitis (CP) and 71,182
      controls without periodontitis. Generalized linear mixed-model analyses were used
      to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      for previous AR diagnosis in patients and controls. RESULTS: Significant
      difference was found in prevalence of prior AR for patients and controls (28.4%
      versus 24.2%; P <0.001). Generalized linear mixed model suggested that the OR of
      previous AR for patients was 1.24 (95% CI: 1.22 to 1.27; P <0.001) compared with
      controls. Adjustments were made for: 1) monthly income; 2) urbanization level; 3)
      diabetes mellitus; 4) hypertension; 5) coronary heart disease; 6) hyperlipidemia;
      7) alcohol abuse; 8) tobacco use disorder; and 9) random effect of geographic
      region. After adjusting, OR of previous AR diagnosis among patients was 1.21 (95%
      CI: 1.18 to 1.23; P <0.001) compared with controls. CONCLUSIONS: An association
      between periodontitis and prior AR is demonstrated. It is recommended that
      physicians be more alert for potential risk of subsequent development of CP in
      patients with AR.

PMID- 27043257
TI  - Effects of C-Terminal Amelogenin Peptide on Proliferation of Human Cementoblast
      Lineage Cells.
AB  - BACKGROUND: Extracts of enamel matrix proteins are used to regenerate periodontal
      tissue; amelogenin, the most abundant enamel protein, plays an important role in
      this regeneration. Studies have demonstrated that amelogenin fragments promote
      tissue regeneration, but the bioactive site of amelogenin remains unclear. This
      study explores the functional domain of amelogenin by investigating effects of
      four amelogenin species on cementoblast proliferation. METHODS: Four amelogenin
      species based on amelogenin cleavage products were investigated: 1) recombinant
      human full-length amelogenin (rh174); 2) amelogenin cleavage product lacking the
      C-terminal (rh163); 3) amelogenin cleavage product lacking the N-terminal
      (rh128); and 4) the C-terminal region of rh174 (C11 peptide), which was
      synthesized and purified. Human cementoblast-like cell line (HCEM) cells were
      cultured and treated with rh174, rh163, rh128, or C11 peptide. Cell proliferation
      was evaluated using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H- tetrazolium assay and cell proliferation enzyme-linked
      immunosorbent assay. Mitogen-activated protein kinase (MAPK)-extracellular signal
      regulated kinase (ERK) (MAPK-ERK) pathway was examined by Western blot analysis.
      RESULTS: Proliferation of HCEM cells was significantly enhanced on treatment with
      rh174, rh128, or C11 peptide. However, rh163 had no effect compared with the
      untreated control group. Western blot analysis revealed enhanced phosphorylated
      ERK1/2 signaling after addition of rh128 or C11 peptide and reduced
      phosphorylated ERK1/2 signaling after blocking with a specific MAPK inhibitor
      (U0126). CONCLUSION: C-terminal amelogenin cleavage product increased
      proliferation of HCEM through MAPK-ERK signaling pathway, indicating possible
      application of C11 peptide for periodontal tissue regeneration.

PMID- 27043258
TI  - Empagliflozin reduces cardiovascular events and mortality in type 2 diabetes.
AB  - Review of: Zinnam, B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular
      Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine.
      2015; 373: 2117-2128. Patients were required to have a history of established
      cardiovascular disease, along with Type 2 Diabetes but were either not on
      antidiabetic therapy for the preceding 12 weeks, with a glycated hemoglobin level
      between 7% and 9%, or were on stable antidiabetic therapy for the preceding 12
      weeks, with a glycated hemoglobin between 7.0% and 10.0%. Patients were
      randomized in a 1:1:1 ratio to either empagliflozin 10 mg or 25 mg or matching
      placebo. Antidiabetic therapy was not to be changed for the first 12 weeks after
      randomization, with intensification of antidiabetic therapy allowed if the
      patient had a confirmed glucose of >240 mg/dl (>13.3 mmol/l). Physicians were
      encouraged to treat other cardiac risk factors like hyperlipidemia according to
      local guidelines. The primary outcome was a composite of death from
      cardiovascular causes, non-fatal myocardial infarction, or nonfatal stroke.
      Results showed a significant reduction in the rates of death from cardiovascular
      causes, overall mortality, and in hospital admissions for heart failure, while
      there was no reduction in the rates of non-fatal myocardial infarction or stroke.

PMID- 27043259
TI  - Synergistic effects of ultraviolet-B and methyl jasmonate on tanshinone
      biosynthesis in Salvia miltiorrhiza hairy roots.
AB  - Tanshinones are major bioactive diterpenoids of Salvia miltiorrhiza roots used
      for the treatment of cardiocerebral diseases. To develop effective elicitation
      and bioprocess strategies for the enhanced production of tanshinones, ultraviolet
      B (UV-B) irradiation and methyl jasmonate (MeJA) elicitation were applied alone
      or in combination respectively in S. miltiorrhiza hairy root cultures. Our
      results showed 40-min UV-B irradiation at 40MUW/cm(2) stimulated tanshinone
      production without any suppression of root growth, suggesting a new effective
      elicitor to S. miltiorrhiza hairy root cultures for tanshinone production.
      Moreover, the combined treatment of UV-B irradiation and MeJA exhibited
      synergistic effects on the expression levels of 3-hydroxy-3-methylglutaryl-CoA
      reductase (SmHMGR) and geranylgeranyl diphosphate synthase (SmGGPPS) genes in the
      tanshinone biosynthetic pathway. When hairy roots of 18-day-old cultures were
      exposed to the combined elicitation for 9days, the maximum production of
      tanshinone reached to 28.21mg/L, a 4.9-fold increase over the control. The
      combined elicitation of UV-B and MeJA was firstly used to stimulate the
      production of biologically important secondary metabolites in hairy root
      cultures. 

PMID- 27043260
TI  - Optimal vitamin D3 daily intake of 2000IU inferred from modeled solar exposure of
      ancestral humans in Northern Tanzania.
AB  - Recently, high serum 25-hydroxyvitamin D concentration (~110nmol/L) was found in
      the Hadza tribe still keeping ancient hunter-gather life style. This level could
      serve as optimal vitamin D level that was built during millennia of human
      evolution. The personal vitamin D3 effective solar exposures of the Hadza adults
      are estimated using radiative model simulations with input from the satellite
      observations over lake Eyasi (3.7 degrees S, 35.0 degrees E). The calculations
      are carried out assuming the Hadza typical clothing habits and specific scenarios
      of the out-door activity comprising early morning and late afternoon working time
      in sun and prolonged midday siesta in the shade. The modeled doses received by
      the Hadza are converted to the vitamin D3 effective daily doses pertaining to the
      lighter skinned persons. We propose a novel formula to get adequate vitamin D
      level - exposure of 1/3 MED around local noon to 1/3 part of the whole body
      during warm sub-period of the year in the low- and mid-latitude regions. Such
      daily solar exposure is equivalent to ~2000IU of vitamin D3 taken orally. For
      many contemporary humans with limited out-door activity habit achieving such
      daily norm requires vitamin D3 supplementation of 2000IU throughout the whole
      year. 

PMID- 27043261
TI  - Beyond alphabet soup: helping college health professionals understand sexual
      fluidity.
AB  - Many college students today are no longer using the terms straight, gay, lesbian,
      bisexual, or transgender to self-identify their sexual orientation or gender
      identity. This commentary explores research related to fluidity of sexual
      identities, emerging sexual identities used by college students, and how these
      identities interact with the health and well-being of the student. Additionally,
      the authors discuss strategies to help college health professionals provide a
      sensitive environment and clinical experience for students whose sexual identity
      is fluid.

PMID- 27043262
TI  - Aiming High--Changing the Trajectory for Cancer.

PMID- 27043263
TI  - The effect of aged litter materials on polyatomic ion concentrations in
      fractionated suspended particulate matter from a broiler house.
AB  - Inorganic emissions from livestock production and subsequent deposition of these
      ions can be a major source of pollution, causing nitrogen enrichment,
      eutrophication, acidification of soils and surface waters, and aerosol formation.
      In the poultry house, ammonia and hydrogen sulfide emissions can also adversely
      affect the health, performance, and welfare of both animals and human operators.
      The persistence and long life expectancy of ammonia, odors and toxic pollutants
      from poultry houses may be due to the ability of suspended particulate matter
      (SPM) to serve as carriers for odorous compounds such as ammonium ions and other
      inorganic compounds (e.g., phosphate, sulfate, nitrate, etc.). SPM is generated
      from the feed, animal manure, and the birds themselves. A large portion of odor
      associated with exhaust air from poultry houses is SPM that has absorbed odors
      from within the houses. Understanding the fate and transport processes of ammonia
      and other inorganic emissions in poultry houses is a necessary first step in
      utilizing the appropriate abatement strategies. In this study, the examination
      and characterization of ammonium ions, major components of odors and toxic gases
      from poultry operations, and other ions in suspended particulate matter in a
      broiler house were carried out using particle trap impactors. The SPM from the
      particle trap impactors was extracted and analyzed for its ionic species using
      ion chromatography (IC). The results showed concentrations of polyatomic ions in
      suspended particulate matter were found to increase with successive flocks and
      were highly concentrated in the larger size particulate matter. In addition, the
      ions concentrations appeared to reach a maximum at the middle of flock age
      (around the fourth week), tapering off toward the end in a given flock (possibly
      due to ventilation rates to cool off larger birds). Thus, it can be inferred that
      aged of bedding materials affects the ionic concentrations in aerosol particulate
      matter more than the age of the birds. IMPLICATIONS: In the poultry house, toxic
      gas emissions can adversely affect the health, performance, and welfare of both
      animals and human operators. The persistence of these toxic pollutants from
      poultry houses may be due to the ability of suspended particulate matter (SPM) to
      serve as carriers for these compounds (inorganic ions). Our study showed that
      polyatomic ions in suspended particulate matter were found to increase with
      successive flocks and were highly concentrated in the larger size SPM.
      Understanding the effect of management practices on poultry air emissions will
      lead to innovative best management practices to safeguard the health and welfare
      of the animals as well as those of the poultry operators, along with reducing the
      impact of potential air pollution on the environment.

PMID- 27043264
TI  - Outpatient-based physical rehabilitation for survivors of prolonged critical
      illness: A randomized controlled trial.
AB  - INTRODUCTION: The physical and psychological impact of critical illness is well
      documented. Recovery may take many months and is often incomplete. The optimal
      way of addressing these important sequelae following hospital discharge remains
      unclear. METHODS: Single center, randomized controlled trial in patients
      invasively ventilated for >=5 days. The treatment group (TG) underwent a 7-week,
      outpatient-based exercise and education program, with the control group (CG)
      receiving no intervention during the study period. Primary outcome measures were
      changes in functional capacity assessed using the cardiopulmonary exercise
      testing parameters, peak VO2, and anaerobic threshold (AT). Secondary outcome
      measures were changes in and health-related quality of life assessed using the
      Short Form 36 version 2 questionnaire. Assessors remained blinded to group
      allocation. RESULTS: Sixty-three patients completed the study (target n = 90).
      Improvements in both peak VO2 and AT were seen in both TG and CG but no
      significant difference between groups was evident. AT improved by 11.7% in CG
      (baseline 10.3 ml O2 kg(-1) min(-1), follow-up 11.5 ml O2 kg(-1) min(-1)), and by
      14.6% in TG (baseline 10.3 ml O2 kg(-1) min(-1), follow-up 11.8 ml O2 kg(-1) min(
      1); ANCOVA p = 0.74). Peak VO2 improved by 14.0% in CG (baseline 13.6 ml O2 kg(
      1) min(-1), follow-up 15.5 ml O2 kg(-1) min(-1)), and by 18.8% in TG (baseline
      13.8 ml O2 kg(-1) min(-1), follow-up 16.4 ml O2 kg(-1) min(-1); ANCOVA p = 0.68).
      Significant improvements were seen in both groups for physical component summary
      scores (PCS) (TG 39.6 versus 31.0; CG 36.1 versus 32.6) and mental component
      summary scores (MCS) (TG 48.6 versus 38.4; CG 41.3 versus 37.0). The degree of
      improvement was significantly higher in the treatment group in comparison to
      control subjects (PCS p = 0.048; MCS p = 0.017). This improvement was most marked
      in the subgroup ventilated for >14 days. CONCLUSIONS: A 7-week, outpatient-based
      exercise and education program resulted in improved health-related quality of
      life scores but not improved exercise capacity.

PMID- 27043265
TI  - Role of pharmacogenetics on deferasirox AUC and efficacy.
AB  - AIM: We evaluated deferasirox pharmacokinetic according to SNPs in genes involved
      in its metabolism and elimination. Moreover, we defined a plasma area under the
      curve cut-off value predicting therapy response. PATIENTS & METHODS: Allelic
      discrimination was performed by real-time PCR. Drug plasma concentrations were
      measured by a high performance liquid chromatography system coupled with an
      ultraviolet method. RESULTS: Pharmacokinetic parameters were significantly
      influenced by UGT1A1 rs887829C>T, UGT1A3 rs1983023C>T and rs3806596A>G SNPs. Area
      under the curve cut-off values of 360 MUg/ml/h for efficacy were here defined and
      250 MUg/ml/h for nonresponse was reported. UGT1A3 rs3806596GG and ABCG2
      rs13120400CC genotypes were factors able to predict efficacy, whereas UGT1A3
      rs3806596GG was a nonresponse predictor. CONCLUSION: These data show how
      screening patient's genetic profile may help clinicians to optimize iron
      chelation therapy with deferasirox.

PMID- 27043266
TI  - How do we measure efficacy of therapy in onychomycosis: Patient, physician, and
      regulatory perspectives.
AB  - BACKGROUND: Onychomycosis is a difficult to treat fungal infection of the nail
      plate. Definitions of treatment outcomes measured in clinical trial settings vary
      widely, preventing the comparison of data across studies. OBJECTIVE: To
      investigate definitions of efficacy measures used in clinical trial settings for
      the treatment of onychomycosis and discuss the importance of consistent
      reporting. METHODS: We searched Pubmed and Ovid for studies in which oral and
      topical drugs were used to treat onychomycosis. RESULTS: The majority of clinical
      trials investigated used mycological and clinical cure to validate efficacy of
      treatment. Mycological cure was almost exclusively defined as negative potassium
      hydroxide (KOH) microscopy and negative culture, whereas clinical cure had a
      variety of definitions ranging from >= 50% clinical improvement to 0% nail plate
      involvement. The majority of efficacies were measured between 48-52 weeks from
      the onset of treatment. CONCLUSION: Clinical cure and almost complete cure
      definitions need to be consistently used across all boards. We have suggested
      definitions for clinical cure, clinical success and clinical improvement.
      Finally, efficacy measures should be completed between 78-104 weeks from onset of
      treatment, if feasible.

PMID- 27043267
TI  - Identification of N-phenyl-2-(N-phenylphenylsulfonamido)acetamides as new
      RORgamma inverse agonists: Virtual screening, structure-based optimization, and
      biological evaluation.
AB  - Retinoic acid receptor-related orphan receptors (RORs) are ligand-dependent
      transcriptional factors and members of the nuclear receptor superfamily. RORs
      regulate inflammation, metabolic disorders and circadian rhythm. RORgamma is a
      promising therapeutic drug target for treating Th17-mediated autoimmune diseases.
      In our study, we performed structure-based virtual screening and ligand-based
      virtual screening targeting the RORgamma ligand-binding domain and successfully
      identified N-phenyl-2-(N-phenylphenylsulfonamido) acetamides as a type of
      RORgamma inverse agonist. Among the 28 purchased compounds, C11 was confirmed to
      be active with micromolar IC50 values in both an AlphaScreen assay (62.58 MUM)
      and a cell-based reporter gene assay (4.54 MUM). Structure-guided optimization of
      the compound C11 led to the identification of compound 39, which significantly
      enhanced RORgamma inhibition with an IC50 value of 630 nM. The RORgamma
      antagonism of 39 was 7-fold higher than that of hit compound C11. These results
      represent a promising starting point for developing potent small molecule
      RORgamma inverse agonists for the treatment of autoimmune diseases, such as
      rheumatoid arthritis, psoriasis, and multiple sclerosis. 

PMID- 27043268
TI  - Design, synthesis, biological evaluation and docking studies of novel 2
      substituted-4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives
      as dual PI3Kalpha/mTOR inhibitors.
AB  - Four series of 2-substituted-4-morpholino- 7,8-dihydro-5H-thiopyrano[4,3
      d]pyrimidine derivatives (9-28) were designed, synthesized and their structures
      were confirmed by (1)H NMR, (13)C NMR and MS spectrum. All compounds were
      evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF
      7). And four selected compounds (10, 11, 24, 27) were further evaluated for the
      IC50 values against PI3Kalpha and mTOR kinases. Seven of the target compounds
      exhibited moderate to excellent antitumor activities against these three cancer
      cell lines. The most promising compound 11 showed good antitumor potency for
      A549, PC-3 and MCF-7 cell lines with IC50 values of 0.52 +/- 0.10 MUM, 1.41 +/-
      0.10 MUM, 4.82 +/- 0.24 MUM and moderate antitumor activities against
      PI3Kalpha/mTOR with IC50 values of 6.72 +/- 0.30 MUM and 0.94 +/- 0.10 MUM.
      Structure-activity relationships (SARs) and docking studies indicated that aryl
      urea scaffolds had a significant impact on the antitumor activities, and aryl
      pyridine urea scaffolds produced the best potency. Variations in substitutions of
      the aryl group had a significant impact on the activity and 3-Cl-4-F or 3-CF3-4
      Cl substitution was more preferred. 

PMID- 27043269
TI  - The chemosensitizing agent lubeluzole binds calmodulin and inhibits
      Ca(2+)/calmodulin-dependent kinase II.
AB  - An affinity capillary electrophoresis (ACE) method to estimate apparent
      dissociation constants between bovine brain calmodulin (CaM) and non-peptidic
      ligands was developed. The method was validated reproducing the dissociation
      constants of a number of well-known CaM ligands. In particular, the potent
      antagonist 125-C9 was ad hoc synthesized through an improved synthetic procedure.
      The ACE method was successfully applied to verify CaM affinity for lubeluzole, a
      well-known neuroprotective agent recently proved useful to potentiate the
      activity of anti-cancer drugs. Lubeluzole was slightly less potent than 125-C9
      (Kd = 2.9 +/- 0.7 and 0.47 +/- 0.06 MUM, respectively) and displayed
      Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibition (IC50 = 40 +/- 1 MUM).
      Possible binding modes of lubeluzole to CaM were explored by docking studies
      based on the X-ray crystal structures of several trifluoperazine-CaM complexes.
      An estimated dissociation constant in good agreement with the experimental one
      was found and the main aminoacidic residues and interactions contributing to
      complex formation were highlighted. The possibility that interference with Ca(2+)
      pathways may contribute to the previously observed chemosensitizing effects of
      lubeluzole on human ovarian adenocarcinoma and lung carcinoma cells are
      discussed. 

PMID- 27043270
TI  - How did life survive Earth's great oxygenation?
AB  - Life on Earth originated and evolved in anoxic environments. Around 2.4 billion
      years-ago, ancestors of Cyanobacteria invented oxygenic photosynthesis, producing
      substantial amounts of O2 as a byproduct of phototrophic water oxidation. The
      sudden appearance of O2 would have led to significant oxidative stress due to
      incompatibilities with core cellular biochemical processes. Here we examine this
      problem through the lens of Cyanobacteria-the first taxa to observe significant
      fluxes of intracellular dioxygen. These early oxygenic organisms likely adapted
      to the oxidative stress by co-opting preexisting systems (exaptation) with
      fortuitous antioxidant properties. Over time more advanced antioxidant systems
      evolved, allowing Cyanobacteria to adapt to an aerobic lifestyle and become the
      most important environmental engineers in Earth history.

PMID- 27043272
TI  - Is harsh caregiving effective in toddlers with low inhibitory control? An
      experimental study in the food domain.
AB  - The aim of our study is to evaluate the validity of the "Caregiving*Temperament
      Paradigm" in the food domain. In this study, two prototypes of caregiving control
      have been contrasted: Harsh (forceful measures to curve the child's behavior)
      versus Gentle control (supportive measures to direct the child's behavior). In
      food domain, the most effective control to help a child to overcome initial
      dislike is repeated exposure. Our first objective was to test whether the
      repeated exposure displayed in a gentle context has a more benefical effect on
      dislike shifting than the one displayed in a harsh context. Our second objective
      was to assess whether this effect was moderated by a temperamental characteristic
      (child's inhibitory control). A randomized experimental protocol was used in day
      care-centers, involving 98 children aged 21-41 months. Children were asked to
      consume an initially rejected target food on five occasions either with a Gentle
      or a Harsh instruction. Children's dislike for the target food was assessed via
      intake before and after the familiarization phase. Inhibitory control level was
      measured in 78 of these children using validated questionnaire. Four groups were
      created: Instructions (Gentle vs Harsh)*Inhibitory control (Lower vs Higher).
      After the familiarization phase, the consumption of the target food increased in
      all groups, but with a higher increase in children with high Inhibitory control
      with Gentle instruction, than for children with low Inhibitory control with Harsh
      instruction, the two other groups being in between. Our data fit a model of
      cumulative effects, and show that both gentle control strategies and high
      inhibitory control in children contribute to regulate disgusts experienced in
      some feeding contexts.

PMID- 27043273
TI  - Skepticism: Genuine unbelief or implicit beliefs in the supernatural?
AB  - We examined whether skeptics hold implicit supernatural beliefs or implicit
      cognitive underpinnings of the beliefs. In study 1 (N=57), participants read a
      biological or a religious story about death. The story content had no effect on
      skeptics' (or believers') afterlife beliefs. Study 2 examined the relationships
      between religious and non-religious paranormal beliefs and implicit views about
      whether supernatural and religious phenomena are imaginary or real (n1=33,
      n2=31). The less supernatural beliefs were endorsed the easier it was to connect
      "supernatural" with "imaginary". Study 3 (N=63) investigated whether
      participants' supernatural beliefs and ontological confusions differ between
      speeded and non-speeded response conditions. Only non-analytical skeptics'
      ontological confusions increased in speeded conditions. The results indicate that
      skeptics overall do not hold implicit supernatural beliefs, but that non
      analytically thinking skeptics may, under supporting conditions, be prone to
      biases that predispose to supernatural beliefs.

PMID- 27043274
TI  - Loss of parvalbumin-immunoreactivity in mouse brain regions after repeated
      intermittent administration of esketamine, but not R-ketamine.
AB  - Clinical use of the rapid antidepressant drug ketamine is limited, due to
      psychotomimetic side effects. R-ketamine appears to be a potent, long-lasting and
      safer antidepressant, relative to S-ketamine (esketamine), since it is free of
      psychotomimetic side effects. Repeated, intermittent administration of esketamine
      (10mg/kg, once per week for 8-weeks), but not R-ketamine, caused loss of
      parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex and hippocampus
      of mouse brains, regions associated with psychosis. This study suggests that
      repeated intermittent use of R-ketamine is safer than esketamine in the treatment
      of depression.

PMID- 27043275
TI  - Dimensional approaches to schizophrenia: A comparison of the Bern Psychopathology
      scale and the five-factor model of the Positive and Negative Syndrome Scale.
AB  - The aim was to examine to what extent the dimensions of the BPS map the five
      factors derived from the PANSS in order to explore the level of agreement of
      these alternative dimensional approaches in patients with schizophrenia. 149
      inpatients with schizophrenia spectrum disorders were recruited.
      Psychopathological symptoms were assessed with the Bern Psychopathology Scale
      (BPS) and the Positive and Negative Syndrome Scale (PANSS). Linear regression
      analyses were conducted to explore the association between the factors and the
      items of the BPS. The robustness of patterns was evaluated. An understandable
      overlap of both approaches was found for positive and negative symptoms and
      excitement. The PANSS positive factor was associated with symptoms of the affect
      domain in terms of both inhibition and disinhibition, the PANSS negative factor
      with symptoms of all three domains of the BPS as an inhibition and the PANSS
      excitement factor with an inhibition of the affect domain and a disinhibition of
      the language and motor domains. The results show that here is only a partial
      overlap between the system-specific approach of the BPS and the five-factor PANSS
      model. A longitudinal assessment of psychopathological symptoms would therefore
      be of interest.

PMID- 27043276
TI  - The effect of brain death and coma on gastric myoelectrical activity.
AB  - BACKGROUND/AIMS: Gastrointestinal motility problems and delayed gastric emptying
      in patients admitted to intensive care units are important because they can
      contribute to different problems. Herein we aimed to measure the changes in
      gastric myoelectrical activity with electrogastrography (EGG) following brain
      death (BD) and compare the results to those from patients in a deep coma without
      BD. MATERIALS AND METHODS: Fifteen patients with BD and nine in a deep coma with
      a Glasgow Coma Score from 3 to 8 were included. An enteral nutrition solution was
      given via a nasogastric tube between 45 min of fasting and the postprandial
      periods. The mean dominant frequency (MnDF), normal gastric slow wave ratio (%),
      tachygastria and bradygastria (%), power ratio (PR: dominant power after test
      meal/fasting), and dominant frequency instability coefficient were evaluated.
      RESULTS: The median of MnDF was determined 3.20+/-0.6 (BD) vs 3.05+/-0.5
      (control), p>0.05. Patients with BD displayed tachygastria, particularly during
      the fasting state, with this disturbance decreasing during the postprandial
      period (from 41% to 15%). However, none of the differences between the groups
      were statistically significant. PR was pathologic in 4/15 (26.7%) patients in the
      BD group and 4/9 (44.4%) patients in the control group (p=0.288). CONCLUSION:
      Patients with coma or BD bouth might have gastric myoelectrical activity
      disturbances. BD does not show more severe disturbance than coma wihouth BD. EGG
      might be useful as a non-invasive and easy-to-use technology; however, it needs
      further improvement.

PMID- 27043277
TI  - Structural Variation in Surface-Supported Synthesis by Adjusting the
      Stoichiometric Ratio of the Reactants.
AB  - Surface-supported coupling reactions between 1,3,5-tris(4-formylphenyl)benzene
      and aromatic amines have been investigated on Au(111) using scanning tunneling
      microscopy under ultra-high-vacuum conditions. Upon annealing to moderate
      temperatures, various products, involving the discrete oligomers and the surface
      covalent organic frameworks, are obtained through thermal-triggered on-surface
      chemical reactions. We conclude from the systematic experiments that the
      stoichiometric composition of the reactants is vital to the surface reaction
      products, which is rarely reported so far. With this knowledge, we have
      successfully prepared two-dimensional covalently bonded networks by optimizing
      the stoichiometric proportions of the reaction precursors.

PMID- 27043278
TI  - ALSUntangled No. 34: GM604.

PMID- 27043279
TI  - Dornase alfa for cystic fibrosis.
AB  - BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary
      disease (the major cause of morbidity and mortality) in cystic fibrosis. It
      reduces mucus viscosity in the lungs, promoting improved clearance of secretions.
      This is an update of a previously published review. OBJECTIVES: To determine
      whether the use of dornase alfa in cystic fibrosis is associated with improved
      mortality and morbidity compared to placebo or other medications that improve
      airway clearance, and to identify any adverse events associated with its use.
      SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders
      Group Trials Register which comprises references identified from comprehensive
      electronic database searches, handsearching relevant journals and abstracts from
      conferences. Date of the most recent search of the Group's Cystic Fibrosis
      Register: 30 November 2015.Clinicaltrials.gov was also searched to identify
      unpublished or ongoing trials. Date of most recent search: 28 November 2015.
      SELECTION CRITERIA: All randomised and quasi-randomised controlled trials
      comparing dornase alfa to placebo, standard therapy or other medications that
      improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently
      assessed trials against the inclusion criteria; two authors carried out analysis
      of methodological quality and data extraction. MAIN RESULTS: The searches
      identified 54 trials, of which 19 (including a total of 2565 participants) met
      our inclusion criteria. Three additional papers examined the healthcare cost from
      one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no
      dornase alfa treatment (2447 participants); two compared daily dornase to
      hypertonic saline (32 participants); one compared daily dornase alfa with
      hypertonic saline and alternate day dornase alfa (48 participants); one compared
      dornase alfa to mannitol and the combination of both drugs (38 participants).
      Trial duration varied from six days to three years.Compared to placebo, forced
      expiratory volume at one second improved in the intervention groups, with
      significant differences at one, three, six months and two years. There was also a
      significant improvement in lung clearance index at one month. There was a
      decrease in pulmonary exacerbations compared to placebo in trials of longer
      duration. The quality of the evidence from placebo-controlled trials was moderate
      to high for outcomes of lung function and pulmonary exacerbations. Limited, low
      quality evidence was available for changes in quality of life from baseline. One
      trial that examined the cost of care, including the cost of dornase alfa, found
      that the cost savings from dornase alfa offset 18% to 38% of the medication
      costs.The results for trials comparing dornase alfa to other medications that
      improve airway clearance (hypertonic saline or mannitol) were mixed, with one
      trial showing a greater improvement in forced expiratory volume at one second for
      dornase alfa compared to hypertonic saline, and three trials finding no
      difference between medications. In the only trial to assess the combination of
      dornase alfa with another medication compared to dornase alone, there was no
      benefit seen with the combination of dornase alfa and mannitol. Evidence of
      dornase alfa compared to other medications was limited and the open-label design
      of the trials may have induced bias, therefore the quality of the evidence was
      judged to be low.Dornase alfa did not cause significantly more adverse effects,
      except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show
      that, compared with placebo, therapy with dornase alfa improves lung function in
      people with cystic fibrosis in trials lasting one month to two years. There was a
      decrease in pulmonary exacerbations in trials of six months or longer. Voice
      alteration and rash appear to be the only adverse events reported with increased
      frequency in randomised controlled trials. There is not enough evidence to firmly
      conclude if dornase alfa is superior to hyperosmolar agents in improving lung
      function.

PMID- 27043280
TI  - c-Met-mediated endothelial plasticity drives aberrant vascularization and
      chemoresistance in glioblastoma.
AB  - Aberrant vascularization is a hallmark of cancer progression and treatment
      resistance. Here, we have shown that endothelial cell (EC) plasticity drives
      aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By
      utilizing human patient specimens, as well as allograft and genetic murine GBM
      models, we revealed that a robust endothelial plasticity in GBM allows
      acquisition of fibroblast transformation (also known as endothelial mesenchymal
      transition [Endo-MT]), which is characterized by EC expression of fibroblast
      markers, and determined that a prominent population of GBM-associated fibroblast
      like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature
      without the loss of EC functions, leading to enhanced cell proliferation and
      migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS
      1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin
      degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition
      induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific
      KO of Met inhibited vascular transformation, normalized blood vessels, and
      reduced intratumoral hypoxia, culminating in suppressed tumor growth and
      prolonged survival in GBM-bearing mice after temozolomide treatment. Together,
      these findings illustrate a mechanism that controls aberrant tumor
      vascularization and suggest that targeting Endo-MT may offer selective and
      efficient strategies for antivascular and vessel normalization therapies in GBM,
      and possibly other malignant tumors.

PMID- 27043281
TI  - A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the
      blood-brain barrier.
AB  - The blood-brain barrier (BBB) protects the brain from toxic substances within the
      peripheral circulation. It maintains brain homeostasis and is a hurdle for drug
      delivery to the CNS to treat neurodegenerative diseases, including Alzheimer's
      disease and brain tumors. The drug efflux transporter P-glycoprotein (P-gp) is
      highly expressed on brain endothelial cells and blocks the entry of most drugs
      delivered to the brain. Here, we show that activation of the A2A adenosine
      receptor (AR) with an FDA-approved A2A AR agonist (Lexiscan) rapidly and potently
      decreased P-gp expression and function in a time-dependent and reversible manner.
      We demonstrate that downmodulation of P-gp expression and function coincided with
      chemotherapeutic drug accumulation in brains of WT mice and in primary mouse and
      human brain endothelial cells, which serve as in vitro BBB models. Lexiscan also
      potently downregulated the expression of BCRP1, an efflux transporter that is
      highly expressed in the CNS vasculature and other tissues. Finally, we determined
      that multiple pathways, including MMP9 cleavage and ubiquitinylation, mediated P
      gp downmodulation. Based on these data, we propose that A2A AR activation on BBB
      endothelial cells offers a therapeutic window that can be fine-tuned for drug
      delivery to the brain and has potential as a CNS drug-delivery technology.

PMID- 27043282
TI  - SOX9 drives WNT pathway activation in prostate cancer.
AB  - The transcription factor SOX9 is critical for prostate development, and
      dysregulation of SOX9 is implicated in prostate cancer (PCa). However, the SOX9
      dependent genes and pathways involved in both normal and neoplastic prostate
      epithelium are largely unknown. Here, we performed SOX9 ChIP sequencing analysis
      and transcriptome profiling of PCa cells and determined that SOX9 positively
      regulates multiple WNT pathway genes, including those encoding WNT receptors
      (frizzled [FZD] and lipoprotein receptor-related protein [LRP] family members)
      and the downstream beta-catenin effector TCF4. Analyses of PCa xenografts and
      clinical samples both revealed an association between the expression of SOX9 and
      WNT pathway components in PCa. Finally, treatment of SOX9-expressing PCa cells
      with a WNT synthesis inhibitor (LGK974) reduced WNT pathway signaling in vitro
      and tumor growth in murine xenograft models. Together, our data indicate that
      SOX9 expression drives PCa by reactivating the WNT/beta-catenin signaling that
      mediates ductal morphogenesis in fetal prostate and define a subgroup of patients
      who would benefit from WNT-targeted therapy.

PMID- 27043283
TI  - Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic
      disease.
AB  - Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote
      osteolytic lesions; however, the identity of these factors is largely unknown.
      Here, we performed a screen of human myeloma cells to identify pro
      osteoclastogenic agents that could potentially serve as therapeutic targets for
      ameliorating MM-associated bone disease. We found that myeloma cells express high
      levels of the matrix metalloproteinase MMP-13 and determined that MMP-13 directly
      enhances osteoclast multinucleation and bone-resorptive activity by triggering
      upregulation of the cell fusogen DC-STAMP. Moreover, this effect was independent
      of the proteolytic activity of the enzyme. Further, in mouse xenograft models,
      silencing MMP-13 expression in myeloma cells inhibited the development of
      osteolytic lesions. In patient cohorts, MMP-13 expression was localized to BM
      associated myeloma cells, while elevated MMP-13 serum levels were able to
      correctly predict the presence of active bone disease. Together, these data
      demonstrate that MMP-13 is critical for the development of osteolytic lesions in
      MM and that targeting the MMP-13 protein - rather than its catalytic activity -
      constitutes a potential approach to mitigating bone disease in affected patients.

PMID- 27043284
TI  - mTORC2 critically regulates renal potassium handling.
AB  - The mTOR pathway orchestrates cellular homeostasis. The rapamycin-sensitive mTOR
      complex (mTORC1) in the kidney has been widely studied; however, mTORC2 function
      in renal tubules is poorly characterized. Here, we generated mice lacking mTORC2
      in the distal tubule (Rictorfl/fl Ksp-Cre mice), which were viable and had no
      obvious phenotype, except for a 2.5-fold increase in plasma aldosterone.
      Challenged with a low-Na+ diet, these mice adequately reduced Na+ excretion;
      however, Rictorfl/fl Ksp-Cre mice rapidly developed hyperkalemia on a high-K+
      diet, despite a 10-fold increase in serum aldosterone levels, implying that
      mTORC2 regulates kaliuresis. Phosphorylation of serum- and glucocorticoid
      inducible kinase 1 (SGK1) and PKC-alpha was absent in Rictorfl/fl Ksp-Cre mice,
      indicating a functional block in K+ secretion activation via ROMK channels.
      Indeed, patch-clamp experiments on split-open tubular segments from the
      transition zone of the late connecting tubule and early cortical collecting duct
      demonstrated that Ba2+-sensitive apical K+ currents were barely detectable in the
      majority of Rictorfl/fl Ksp-Cre mice. Conversely, epithelial sodium channel
      (ENaC) activity was largely preserved, suggesting that the reduced ability to
      maintain K+ homeostasis is the result of impaired apical K+ conductance and not a
      reduced electrical driving force for K+ secretion. Thus, these data unravel a
      vital and nonredundant role of mTORC2 for distal tubular K+ handling.

PMID- 27043285
TI  - Targeting mitochondrial biogenesis to overcome drug resistance to MAPK
      inhibitors.
AB  - Targeting multiple components of the MAPK pathway can prolong the survival of
      patients with BRAFV600E melanoma. This approach is not curative, as some BRAF
      mutated melanoma cells are intrinsically resistant to MAPK inhibitors (MAPKi). At
      the systemic level, our knowledge of how signaling pathways underlie drug
      resistance needs to be further expanded. Here, we have shown that intrinsically
      resistant BRAF-mutated melanoma cells with a low basal level of mitochondrial
      biogenesis depend on this process to survive MAPKi. Intrinsically resistant cells
      exploited an integrated stress response, exhibited an increase in mitochondrial
      DNA content, and required oxidative phosphorylation to meet their bioenergetic
      needs. We determined that intrinsically resistant cells rely on the genes
      encoding TFAM, which controls mitochondrial genome replication and transcription,
      and TRAP1, which regulates mitochondrial protein folding. Therefore, we targeted
      mitochondrial biogenesis with a mitochondrium-targeted, small-molecule HSP90
      inhibitor (Gamitrinib), which eradicated intrinsically resistant cells and
      augmented the efficacy of MAPKi by inducing mitochondrial dysfunction and
      inhibiting tumor bioenergetics. A subset of tumor biopsies from patients with
      disease progression despite MAPKi treatment showed increased mitochondrial
      biogenesis and tumor bioenergetics. A subset of acquired drug-resistant melanoma
      cell lines was sensitive to Gamitrinib. Our study establishes mitochondrial
      biogenesis, coupled with aberrant tumor bioenergetics, as a potential therapy
      escape mechanism and paves the way for a rationale-based combinatorial strategy
      to improve the efficacy of MAPKi.

PMID- 27043286
TI  - NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase
      PTPN22.
AB  - Inflammasomes form as the result of the intracellular presence of danger
      associated molecular patterns and mediate the release of active IL-1beta, which
      influences a variety of inflammatory responses. Excessive inflammasome activation
      results in severe inflammatory conditions, but physiological IL-1beta secretion
      is necessary for intestinal homeostasis. Here, we have described a mechanism of
      NLRP3 inflammasome regulation by tyrosine phosphorylation of NLRP3 at Tyr861. We
      demonstrated that protein tyrosine phosphatase non-receptor 22 (PTPN22), variants
      in which are associated with chronic inflammatory disorders, dephosphorylates
      NLRP3 upon inflammasome induction, allowing efficient NLRP3 activation and
      subsequent IL-1beta release. In murine models, PTPN22 deficiency resulted in
      pronounced colitis, increased NLRP3 phosphorylation, but reduced levels of mature
      IL-1beta. Conversely, patients with inflammatory bowel disease (IBD) that carried
      an autoimmunity-associated PTPN22 variant had increased IL-1beta levels.
      Together, our results identify tyrosine phosphorylation as an important
      regulatory mechanism for NLRP3 that prevents aberrant inflammasome activation.

PMID- 27043287
TI  - What do monoamines do in pain modulation?
AB  - PURPOSE OF REVIEW: Here, we give a topical overview of the ways in which brain
      processing can alter spinal pain transmission through descending control
      pathways, and how these change in pain states. We link preclinical findings on
      the transmitter systems involved and discuss how the monoamines, noradrenaline, 5
      hydroxytryptamine (5-HT), and dopamine, can interact through inhibitory and
      excitatory pathways. RECENT FINDINGS: Descending pathways control sensory events
      and the actions of the neurotransmitters noradrenaline and 5-HT in the dorsal
      horn of the spinal cord are chiefly implicated in nociception or antinociception
      according to the receptor that is activated. Abnormalities in descending controls
      effect central pain processing. Following nerve injury a noradrenaline-mediated
      control of spinal excitability is lost, whereas its restoration reduces
      neuropathic hypersensitivity. The story with 5-HT remains more complex because of
      the myriad of receptors that it can act upon; however the most recent findings
      support that facilitations may dominate over inhibitions. SUMMARY: The
      monoaminergic system can be manipulated to great effect in the clinic resulting
      in improved treatment outcomes and is the basis for the actions of the
      antidepressant drugs in pain. Looking to the future, prediction of treatment
      responses will possible by monitoring a form of inhibitory descending control for
      optimized pain relief.

PMID- 27043288
TI  - Impact of chemotherapy on cancer-related fatigue and cytokines in 1312 patients:
      a systematic review of quantitative studies.
AB  - PURPOSE OF REVIEW: Cancer-related fatigue (CRF) is the most common psychosomatic
      distress experienced by cancer patients before, during and after chemotherapy.
      Its impact on functional status and Health Related Quality of Life is a great
      concern among patients, healthcare professionals and researchers. The primary
      objective of this systematic review is to determine whether the different
      chemotherapies affect the association of CRF with individual pro- and anti
      inflammatory cytokines. The PRISMA statement guideline has been followed to
      systematically search and screen article from PubMed and Embase. RECENT FINDINGS:
      This review has examined 14 studies which included a total of 1312 patients.
      These studies assayed 20 different kinds of cytokines. The cytokines interleukin
      6, interleukin-1RA, TGF-beta and sTNF-R2 were associated with CRF in patients
      receiving anthracycline-based chemotherapy. However, only interleukin-13 was
      identified in the taxane-based chemotherapy. Similarly, different sets of
      cytokines were linked with CRF in patients with chemotherapy regimens containing
      platinum, cyclophosphamides, topotecan or bleomycin. SUMMARY: This review has
      identified that cytokines are differentially linked with CRF according to the
      various types of chemotherapy regimens.

PMID- 27043289
TI  - Phalangeal Lengthening Techniques for Brachydactily and Posttraumatic Digital
      Stumps With the Use of a Modified External Mini-Fixator.
AB  - Distraction osteogenesis has become the most used method for bone lengthening and
      deformity correction including the bones of the hand and foot. The principle
      techniques used for hand bone lengthening in posttraumatic and congenital
      conditions using available external fixators are based on this method. We present
      the technical specifications and surgical techniques with the use of a mini
      fixator that was specially designed for short tubular bones. The surgical
      techniques of lengthening and web space skin stock creation for future web-pasty
      are supplied with the diagrams of their application to phalanges and illustrative
      clinical cases. Between 1999 and 2012, this mini-fixator was used for lengthening
      of 223 finger segments at our hospital and provided improvement of the hand
      esthetics and functions. 

PMID- 27043290
TI  - A GABAergic nigrotectal pathway for coordination of drinking behavior.
AB  - The contribution of basal ganglia outputs to consummatory behavior remains poorly
      understood. We recorded from the substantia nigra pars reticulata (SNR), the
      major basal ganglia output nucleus, during self-initiated drinking in mice. The
      firing rates of many lateral SNR neurons were time-locked to individual licks.
      These neurons send GABAergic projections to the deep layers of the orofacial
      region of the lateral tectum (superior colliculus, SC). Many tectal neurons were
      also time-locked to licking, but their activity was usually in antiphase with
      that of SNR neurons, suggesting inhibitory nigrotectal projections. We used
      optogenetics to selectively activate the GABAergic nigrotectal afferents in the
      deep layers of the SC. Photo-stimulation of the nigrotectal projections
      transiently inhibited the activity of the lick-related tectal neurons, disrupted
      their licking-related oscillatory pattern and suppressed self-initiated drinking.
      These results demonstrate that GABAergic nigrotectal projections have a crucial
      role in coordinating drinking behavior.

PMID- 27043291
TI  - Using Language Sample Analysis to Assess Spoken Language Production in
      Adolescents.
AB  - PURPOSE: This tutorial discusses the importance of language sample analysis and
      how Systematic Analysis of Language Transcripts (SALT) software can be used to
      simplify the process and effectively assess the spoken language production of
      adolescents. METHOD: Over the past 30 years, thousands of language samples have
      been collected from typical speakers, aged 3-18 years, in conversational and
      narrative contexts. These samples have been formatted as reference databases
      included with SALT. Using the SALT software, individual samples are compared with
      age- and grade-matched samples selected from these databases. RESULTS: Two case
      studies illustrate that comparison with database samples of typical adolescents,
      matched by grade and elicitation context, highlights language measures that are
      higher or lower than the database mean values. Differences in values are measured
      in standard deviations. CONCLUSION: Language sample analysis remains a powerful
      method of documenting language use in everyday speaking situations. A sample of
      talking reveals an individual's ability to meet specific speaking demands. These
      demands vary across contexts, and speakers can have difficulty in any one or all
      of these communication tasks. Language use for spoken communication is a
      foundation for literacy attainment and contributes to success in navigating
      relationships for school, work, and community participation.

PMID- 27043292
TI  - Reply to "Solid Renal Cell Carcinomas With an Attenuation Similar to That of
      Water on Unenhanced CT".

PMID- 27043293
TI  - The Impact of 3:1 Ketogenic Diet on Cardiac Repolarization Changes in Children
      with Refractory Seizures: A Prospective Follow-Up Study.
AB  - Background The association between ketogenic diet (KD) and prolonged QT interval,
      life-threatening ventricular arrhythmias, and sudden death is controversial. Aim
      We aimed to prospectively evaluate the effect of KD on electrocardiography (ECG)
      measures in children with refractory epilepsy. Method A total of 70 children with
      drug-resistant epilepsy who received a KD for at least 12 months were included in
      the study. The standard 12-lead electrocardiography was performed in all patients
      before the beginning and in the 12th month of KD. Heart rate, P-wave duration and
      dispersion, corrected QT interval and QT dispersion, and Tp-e interval were
      measured. Results All ECG-derived parameters, but P-wave dispersion increased
      after 12 months of KD compared with the baseline values. However, these changes
      were not statistically significant. Conclusion A 12-month long 3:1 KD treatment
      exerts no deleterious effect on cardiac repolarization measures. 

PMID- 27043294
TI  - Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement
      Disorder in Progressed Stages of Late-Infantile CLN2 Disease.
AB  - Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare
      autosomal-recessive lysosomal storage disorder. It is one of the most common
      neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor
      and language regression, dementia, visual loss, and a complex movement disorder
      in later stages of the disease. We report on two children with genetically
      confirmed late-infantile CLN2 disease who developed a severe exacerbation of
      their complex movement disorder leading to hyperthermia, hyper-CK-emia and
      decreased level of consciousness over several weeks despite different therapeutic
      approaches. Both patients were on long-term antiepileptic treatment with
      valproate and only after the withdrawal of valproate, the movement disorder
      disappeared and level of consciousness improved. These observations emphasize
      that valproate has to be considered as a possible risk factor in patients in
      later stages of late-infantile CLN2 disease who develop a rapidly progressive
      complex movement disorder. 

PMID- 27043295
TI  - Lentivirus-Mediated Knockdown of CTHRC1 Inhibits Osteosarcoma Cell Proliferation
      and Migration.
AB  - Collagen triple helix repeat containing-1 (CTHRC1), a secreted protein, is
      transiently expressed in the arterial wall in response to injury, indicating that
      it may contribute to vascular remodeling by limiting collagen matrix deposition
      and promoting cell migration. Recent studies showed that it is aberrantly
      upregulated in most human solid tumors, yet its role in osteosarcoma remains
      unclear. In this study, the authors investigated the role of CTHRC1 in human
      osteosarcoma tumorigenesis. The authors used lentivirus-mediated short hairpin
      RNA (shRNA) against CTHRC1 to limit its endogenous expression in U2OS and SW1353
      cells. Interestingly, they found that depletion of CTHRC1 significantly inhibited
      cell proliferation and colony formation in U2OS and SW1353 cells. Flow cytometry
      assay showed that knockdown of CTHRC1 increased the cell percentage of G0/G1
      phase, resulting in cell cycle arrest in U2OS cells. Moreover, CTHRC1 silencing
      induced the cell cycle arrest by a decrease in the cell percentage in G0/G1 phase
      and increased in G2/M phase in SW1353 cells. In addition, crystal violet staining
      suggested CTHRC1 silencing inhibited migration of U2OS and SW1353 cells. These
      results demonstrated that CTHRC1 might play an important role in osteosarcoma
      progression. 

PMID- 27043296
TI  - SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and
      cellular senescence.
AB  - Pericentric heterochromatin silencing at mammalian centromeres is essential for
      mitotic fidelity and genomic stability. Defective pericentric silencing has been
      observed in senescent cells, aging tissues, and mammalian tumors, but the
      underlying mechanisms and functional consequences of these defects are unclear.
      Here, we uncover an essential role of the human SIRT6 enzyme in pericentric
      transcriptional silencing, and we show that this function protects against
      mitotic defects, genomic instability, and cellular senescence. At pericentric
      heterochromatin, SIRT6 promotes deacetylation of a new substrate, residue K18 of
      histone H3 (H3K18), and inactivation of SIRT6 in cells leads to H3K18
      hyperacetylation and aberrant accumulation of pericentric transcripts.
      Strikingly, depletion of these transcripts through RNA interference rescues the
      mitotic and senescence phenotypes of SIRT6-deficient cells. Together, our
      findings reveal a new function for SIRT6 and regulation of acetylated H3K18 at
      heterochromatin, and demonstrate the pathogenic role of deregulated pericentric
      transcription in aging- and cancer-related cellular dysfunction.

PMID- 27043297
TI  - Structural basis for specific inhibition of Autotaxin by a DNA aptamer.
AB  - ATX is a plasma lysophospholipase D that hydrolyzes lysophosphatidylcholine (LPC)
      and produces lysophosphatidic acid. To date, no ATX-inhibition-mediated treatment
      strategies for human diseases have been established. Here, we report anti-ATX DNA
      aptamers that inhibit ATX with high specificity and efficacy. We solved the
      crystal structure of ATX in complex with the anti-ATX aptamer RB011, at 2.0-A
      resolution. RB011 binds in the vicinity of the active site through base-specific
      interactions, thus preventing the access of the choline moiety of LPC substrates.
      Using the structural information, we developed the modified anti-ATX DNA aptamer
      RB014, which exhibited in vivo efficacy in a bleomycin-induced pulmonary fibrosis
      mouse model. Our findings reveal the structural basis for the specific inhibition
      of ATX by the anti-ATX aptamer and highlight the therapeutic potential of anti
      ATX aptamers for the treatment of human diseases, such as pulmonary fibrosis.

PMID- 27043299
TI  - Provocation Challenges to Evaluate Amoxicillin Allergy in Children.

PMID- 27043298
TI  - Molecular basis of caspase-1 polymerization and its inhibition by a new capping
      mechanism.
AB  - Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic
      and extrinsic danger signals, and trigger inflammatory responses and pyroptotic
      cell death. Homotypic interactions among Pyrin domains and caspase recruitment
      domains (CARDs) in inflammasome-complex components mediate oligomerization into
      filamentous assemblies. Several cytosolic proteins consisting of only interaction
      domains exert inhibitory effects on inflammasome assembly. In this study, we
      determined the structure of the human caspase-1 CARD domain (caspase-1(CARD))
      filament by cryo-electron microscopy and investigated the biophysical properties
      of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or
      CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1
      filaments, thereby exerting potent inhibition with low-nanomolar Ki on caspase
      1(CARD) polymerization in vitro and inflammasome activation in cells. Whereas
      caspase-1(CARD) uses six complementary surfaces of three types for filament
      assembly, INCA is defective in two of the six interfaces and thus terminates the
      caspase-1 filament.

PMID- 27043300
TI  - Enantioselective intramolecular cyclization of alkynyl esters catalyzed by a
      chiral Bronsted base.
AB  - An enantioselective intramolecular cyclization reaction of alkynyl esters was
      developed, which employs a Bronsted base catalyst generated in situ from a chiral
      Schiff base and t-BuOK. This reaction is a rare example of the enantioselective
      intramolecular addition of simple ester enolates to alkynes under Bronsted base
      catalysis. 

PMID- 27043301
TI  - Aerosol-Assisted CVD-Grown PdO Nanoparticle-Decorated Tungsten Oxide Nanoneedles
      Extremely Sensitive and Selective to Hydrogen.
AB  - We report for the first time the successful synthesis of palladium (Pd)
      nanoparticle (NP)-decorated tungsten trioxide (WO3) nanoneedles (NNs) via a two
      step aerosol-assisted chemical vapor deposition approach. Morphological,
      structural, and elemental composition analysis revealed that a Pd(acac)2
      precursor was very suitable to decorate WO3 NNs with uniform and well-dispersed
      PdO NPs. Gas-sensing results revealed that decoration with PdO NPs led to an
      ultrasensitive and selective hydrogen (H2) gas sensor (sensor response peaks at
      1670 at 500 ppm of H2) with low operating temperature (150  degrees C). The
      response of decorated NNs is 755 times higher than that of bare WO3 NNs.
      Additionally, at a temperature near that of the ambient temperature (50  degrees
      C), the response of this sensor toward the same concentration of H2 was 23, which
      is higher than that of some promising sensors reported in the literature.
      Finally, humidity measurements showed that PdO/WO3 sensors displayed low-cross
      sensitivity toward water vapor, compared to bare WO3 sensors. The addition of PdO
      NPs helps to minimize the effect of ambient humidity on the sensor response.

PMID- 27043302
TI  - A Flawed Revision of the Common Rule.

PMID- 27043303
TI  - Gender Differences in Physical Performance Characteristics of Elite Surfers.
AB  - Parsonage, JR, Secomb, JL, Tran, TT, Farley, ORL, Nimphius, S, Lundgren, L, and
      Sheppard, JM. Gender differences in physical performance characteristics of elite
      surfers. J Strength Cond Res 31(9): 2417-2422, 2017-The purpose of this study was
      to describe and compare the gender differences in physical performance
      characteristics of elite surfers. Twenty competitive female surfers (CFS) and 20
      competitive male surfers (CMS) performed a battery of physical performance tests:
      squat jump (SJ), isometric midthigh pull (IMTP), 15-m sprint paddle, and 400-m
      endurance paddle during a single testing session. All performance measures were
      significantly different between CFS and CMS (p < 0.01). Specifically, CMS
      produced greater peak force production (28.5%) and jumped higher (27.7%) in the
      SJ and produced greater normalized peak force during the IMTP (18.9%) compared
      with CFS. For paddling performance, CMS were faster over 5, 10, and 15 m (12.4%,
      9.7%, and 10.9%), possessed a higher peak paddling velocity (11.3%), and recorded
      faster paddle times over 400 m (11.8%). The results of this study suggest that
      CMS exhibit superior physical performance characteristics than CFS, in relation
      to both the lower and upper body. Strength and conditioning practitioners should
      therefore implement a structured and periodized program to facilitate strength
      qualities that underpin surfing performance for all participants, but as
      highlighted in the current investigation, female surfers may have a greater
      window for adaptation and therefore vast benefit of targeting their
      underdeveloped physical qualities.

PMID- 27043304
TI  - Understanding the interaction between energetic ions and freestanding graphene
      towards practical 2D perforation.
AB  - We report experimentally and theoretically the behavior of freestanding graphene
      subjected to bombardment of energetic ions, investigating the capability of large
      scale patterning of freestanding graphene with nanometer sized features by
      focused ion beam technology. A precise control over the He(+) and Ga(+)
      irradiation offered by focused ion beam techniques enables investigating the
      interaction of the energetic particles and graphene suspended with no support and
      allows determining sputter yields of the 2D lattice. We found a strong dependency
      of the 2D sputter yield on the species and kinetic energy of the incident ion
      beams. Freestanding graphene shows material semi-transparency to He(+) at high
      energies (10-30 keV) allowing the passage of >97% He(+) particles without
      creating destructive lattice vacancy. Large Ga(+) ions (5-30 keV), in contrast,
      collide far more often with the graphene lattice to impart a significantly higher
      sputter yield of ~50%. Binary collision theory applied to monolayer and few-layer
      graphene can successfully elucidate this collision mechanism, in great agreement
      with experiments. Raman spectroscopy analysis corroborates the passage of a large
      fraction of He(+) ions across graphene without much damaging the lattice whereas
      several colliding ions create single vacancy defects. Physical understanding of
      the interaction between energetic particles and suspended graphene can
      practically lead to reproducible and efficient pattern generation of
      unprecedentedly small features on 2D materials by design, manifested by our
      perforation of sub-5 nm pore arrays. This capability of nanometer-scale precision
      patterning of freestanding 2D lattices shows the practical applicability of
      focused ion beam technology to 2D material processing for device fabrication and
      integration. 

PMID- 27043305
TI  - Phenotypic Variability of Childhood Charcot-Marie-Tooth Disease.
AB  - IMPORTANCE: Disease severity of childhood Charcot-Marie-Tooth disease (CMT) has
      not been extensively characterized, either within or between types of CMT to
      date. OBJECTIVE: To assess the variability of disease severity in a large cohort
      of children and adolescents with CMT. DESIGN, SETTING, AND PARTICIPANTS: A cross
      sectional study was conducted among 520 children and adolescents aged 3 to 20
      years at 8 universities and hospitals involved in the Inherited Neuropathies
      Consortium between August 6, 2009, and July 31, 2014, in Australia, Italy, the
      United Kingdom, and the United States. Data analysis was conducted from August 1,
      2014, to December 1, 2015. MAIN OUTCOMES AND MEASURES: Scores on the Charcot
      Marie-Tooth Disease Pediatric Scale (CMTPedS), a well-validated unidimensional
      clinical outcome measure to assess disease severity. This instrument includes 11
      items assessing fine and gross motor function, sensation, and balance to produce
      a total score ranging from 0 (unaffected) to 44 (severely affected). RESULTS:
      Among the 520 participants (274 males) aged 3 to 20 years, CMT type 1A (CMT1A)
      was the most prevalent type (252 [48.5%]), followed by CMT2A (31 [6.0%]), CMT1B
      (15 [2.9%]), CMT4C (13 [2.5%]), and CMTX1 (10 [1.9%]). Disease severity ranged
      from 1 to 44 points on the CMTPedS (mean [SD], 21.5 [8.9]), with ankle
      dorsiflexion strength and functional hand dexterity test being most affected.
      Participants with CMT1B (mean [SD] CMTPedS score, 24.0 [7.4]), CMT2A (29.7
      [7.1]), and CMT4C (29.8 [8.6]) were more severely affected than those with CMT1A
      (18.9 [7.7]) and CMTX1 (males: 15.3 [7.7]; females: 13.0 [3.6]) (P < .05). Scores
      on the CMTPedS tended to worsen principally during childhood (ages, 3-10 years)
      for participants with CMT4C and CMTX1 and predominantly during adolescence for
      those with CMT1B and CMT2A (ages, 11-20 years), while CMT1A worsened consistently
      throughout childhood and adolescence. For individual items, participants with
      CMT4C recorded more affected functional dexterity test scores than did those with
      all other types of CMT (P < .05). Participants with CMT1A and CMTX1 performed
      significantly better on the 9-hole peg test and balance test than did those with
      all other types of CMT (P < .05). Participants with CMT2A had the weakest grip
      strength (P < .05), while those with CMT2A and CMT4C exhibited the weakest ankle
      plantarflexion and dorsiflexion strength, as well as the lowest long jump and 6
      minute walk test distances (P < .05). Multiple regression modeling identified
      increasing age (r = 0.356, beta = 0.617, P < .001) height (r = 0.251, beta =
      0.309, P = .002), self-reported foot pain (r = 0.162, beta = .114, P = .009), and
      self-reported hand weakness (r = 0.243, beta = 0.203, P < .001) as independent
      predictors of disease severity. CONCLUSIONS AND RELEVANCE: These results
      highlight the phenotypic variability within CMT genotypes and mutation-specific
      manifestations between types. This study has identified distinct functional
      limitations and self-reported impairments to target in future therapeutic trials.

PMID- 27043306
TI  - Heart Rate Variability and Autonomic Modulations in Preeclampsia.
AB  - BACKGROUND: Although the exact pathophysiology of preeclampsia is not well
      understood, autonomic nervous system imbalance is suggested as one of the main
      factors. AIMS: To investigate heart rate variability (HRV) and autonomic
      modulations in Sudanese pregnant women with preeclampsia. SUBJECTS AND METHODS: A
      case-control study (60 women in each arm) was conducted at Omdurman Maternity
      Hospital-Sudan, during the period from June to August, 2014. Cases were women
      presented with preeclampsia and healthy pregnant women were the controls. Studied
      groups were matched for important determinants of HRV. Natural logarithm (Ln) of
      total power (TP), high frequency (HF), low frequency (LF) and very low frequency
      (VLF) were used to determine HRV. Normalized low and high frequencies (LF Norm
      and HF Norm) were used to evaluate sympathetic and parasympathetic autonomic
      modulations respectively. RESULTS: Patients with preeclampsia achieved
      significantly higher LF Norm [49.80 (16.25) vs. 44.55 (19.15), P = 0.044] and
      LnLF/HF [0.04 (0.68) vs. -0.28 (0.91), P = 0.023] readings, but lower HF Norm
      [49.08 (15.29) vs. 55.87 (19.56), P = 0.012], compared with healthy pregnant
      women. Although all other HRV measurements were higher in the patients with
      preeclampsia compared with the controls, only LnVLF [4.50 (1.19) vs. 4.01 (1.06),
      P = 0.017] and LnLF [4.01 (1.58) vs. 3.49 (1.23), P = 0.040] reached statistical
      significance. CONCLUSION: The study adds further evidence for the dominant
      cardiac sympathetic modulations on patients with preeclampsia, probably secondary
      to parasympathetic withdrawal in this group. However, the higher LnVLF and LnLF
      readings achieved by preeclamptic women compared with the controls are unexpected
      in the view that augmented sympathetic modulations usually depresses all HRV
      parameters including these two measures.

PMID- 27043307
TI  - Aptamer-Assisted Detection of the Altered Expression of Estrogen Receptor Alpha
      in Human Breast Cancer.
AB  - An increase in the expression of estrogen receptors (ER) and the expanded
      population of ER-positive cells are two common phenotypes of breast cancer.
      Detection of the aberrantly expressed ERalpha in breast cancer is carried out
      using ERalpha-antibodies and radiolabelled ligands to make decisions about cancer
      treatment and targeted therapy. Capitalizing on the beneficial advantages of
      aptamer over the conventional antibody or radiolabelled ligand, we have
      identified a DNA aptamer that selectively binds and facilitates the detection of
      ERalpha in human breast cancer tissue sections. The aptamer is identified using
      the high throughput sequencing assisted SELEX screening. Biophysical
      characterization confirms the binding and formation of a thermodynamically stable
      complex between the identified DNA aptamer (ERaptD4) and ERalpha (Ka = 1.55+/
      0.298*108 M(-1); DeltaH = 4.32*104+/-801.1 cal/mol; DeltaS = -108 cal/mol/deg).
      Interestingly, the specificity measurements suggest that the ERaptD4 internalizes
      into ERalpha-positive breast cancer cells in a target-selective manner and
      localizes specifically in the nuclear region. To harness these characteristics of
      ERaptD4 for detection of ERalpha expression in breast cancer samples, we
      performed the aptamer-assisted histochemical analysis of ERalpha in tissue
      samples from breast cancer patients. The results were validated by performing the
      immunohistochemistry on same samples with an ERalpha-antibody. We found that the
      two methods agree strongly in assay output (kappa value = 0.930, p-value <0.05
      for strong ERalpha positive and the ERalpha negative samples; kappa value =
      0.823, p-value <0.05 for the weak/moderate ER+ve samples, n = 20). Further, the
      aptamer stain the ERalpha-positive cells in breast tissues without cross-reacting
      to ERalpha-deficient fibroblasts, adipocytes, or the inflammatory cells. Our
      results demonstrate a significant consistency in the aptamer-assisted detection
      of ERalpha in strong ERalpha positive, moderate ERalpha positive and ERalpha
      negative breast cancer tissues. We anticipate that the ERaptD4 aptamer targeting
      ERalpha may potentially be used for an efficient grading of ERalpha expression in
      cancer tissues.

PMID- 27043308
TI  - Stereoselective Total Synthesis of Bioactive Marine Natural Product
      Biselyngbyolide B.
AB  - A convergent strategy for the stereoselective total synthesis of biologically
      active marine natural product biselyngbyolide B has been developed. Key
      strategies of this synthesis include Jamison protocol of trans
      hydroalumination/allylation for installation of C18-C23 olefin moiety and
      intramolecular Heck coupling for macrocyclization. 

PMID- 27043309
TI  - Governing Equations of Tissue Modelling and Remodelling: A Unified Generalised
      Description of Surface and Bulk Balance.
AB  - Several biological tissues undergo changes in their geometry and in their bulk
      material properties by modelling and remodelling processes. Modelling synthesises
      tissue in some regions and removes tissue in others. Remodelling overwrites old
      tissue material properties with newly formed, immature tissue properties. As a
      result, tissues are made up of different "patches", i.e., adjacent tissue regions
      of different ages and different material properties, within evolving boundaries.
      In this paper, generalised equations governing the spatio-temporal evolution of
      such tissues are developed within the continuum model. These equations take into
      account nonconservative, discontinuous surface mass balance due to creation and
      destruction of material at moving interfaces, and bulk balance due to tissue
      maturation. These equations make it possible to model patchy tissue states and
      their evolution without explicitly maintaining a record of when/where resorption
      and formation processes occurred. The time evolution of spatially averaged tissue
      properties is derived systematically by integration. These spatially-averaged
      equations cannot be written in closed form as they retain traces that tissue
      destruction is localised at tissue boundaries. The formalism developed in this
      paper is applied to bone tissues, which exhibit strong material heterogeneities
      due to their slow mineralisation and remodelling processes. Evolution equations
      are proposed in particular for osteocyte density and bone mineral density.
      Effective average equations for bone mineral density (BMD) and tissue mineral
      density (TMD) are derived using a mean-field approximation. The error made by
      this approximation when remodelling patchy tissue is investigated. The specific
      signatures of the time evolution of BMD or TMD during remodelling events are
      exhibited. These signatures may provide a way to detect remodelling events at
      lower, unseen spatial resolutions from microCT scans. 

PMID- 27043310
TI  - The Effects of Selective Dorsal Rhizotomy on Balance and Symmetry of Gait in
      Children with Cerebral Palsy.
AB  - AIM: Cerebral palsy (CP) is associated with dysfunction of the upper motor neuron
      and results in balance problems and asymmetry during locomotion. Selective dorsal
      rhizotomy (SDR) is a surgical procedure that results in reduced afferent
      neuromotor signals from the lower extremities with the aim of improving gait. Its
      influence on balance and symmetry has not been assessed. The aim of this
      prospective cohort study was to evaluate the impact of SDR on balance and
      symmetry during walking. METHODS: 18 children (10 girls, 8 boys; age 6 years (y)
      3 months (m), SD 1y 8m) with bilateral spastic CP and Gross Motor Function
      Classification System levels I to II underwent gait analysis before and 6 to 12
      months after SDR. Results were compared to 11 typically developing children (TDC;
      6 girls, 5 boys; age 6y 6m, SD 1y 11m). To analyse balance, sway velocity, radial
      displacement and frequency were calculated. Symmetry ratios were calculated for
      balance measures and spatio-temporal parameters during walking. RESULTS: Most
      spatio-temporal parameters of gait, as well as all parameters of balance,
      improved significantly after SDR. Preoperative values of symmetry did not vary
      considerably between CP and TDC group and significant postoperative improvement
      did not occur. INTERPRETATION: The reduction of afferent signalling through SDR
      improves gait by reducing balance problems rather than enhancing movement
      symmetry.

PMID- 27043311
TI  - Physiological Limits along an Elevational Gradient in a Radiation of Montane
      Ground Beetles.
AB  - A central challenge in ecology and biogeography is to determine the extent to
      which physiological constraints govern the geographic ranges of species along
      environmental gradients. This study tests the hypothesis that temperature and
      desiccation tolerance are associated with the elevational ranges of 12 ground
      beetle species (genus Nebria) occurring on Mt. Rainier, Washington, U.S.A.
      Species from higher elevations did not have greater cold tolerance limits than
      lower-elevation species (all species ranged from -3.5 to -4.1 degrees C), despite
      a steep decline in minimum temperature with elevation. Although heat tolerance
      limits varied among species (from 32.0 to 37.0 degrees C), this variation was not
      generally associated with the relative elevational range of a species.
      Temperature gradients and acute thermal tolerance do not support the hypothesis
      that physiological constraints drive species turnover with elevation.
      Measurements of intraspecific variation in thermal tolerance limits were not
      significant for individuals taken at different elevations on Mt. Rainier, or from
      other mountains in Washington and Oregon. Desiccation resistance was also not
      associated with a species' elevational distribution. Our combined results
      contrast with previously-detected latitudinal gradients in acute physiological
      limits among insects and suggest that other processes such as chronic thermal
      stress or biotic interactions might be more important in constraining elevational
      distributions in this system. 

PMID- 27043312
TI  - Development of a new instrument for determining the level of chewing function in
      children.
AB  - This study aimed to develop a chewing performance scale that classifies chewing
      from normal to severely impaired and to investigate its validity and reliability.
      The study included the developmental phase and reported the content, structural,
      criterion validity, interobserver and intra-observer reliability of the chewing
      performance scale, which was called the Karaduman Chewing Performance Scale
      (KCPS). A dysphagia literature review, other questionnaires and clinical
      experiences were used in the developmental phase. Seven experts assessed the
      steps for content validity over two Delphi rounds. To test structural, criterion
      validity, interobserver and intra-observer reliability, two swallowing therapists
      evaluated chewing videos of 144 children (Group I: 61 healthy children without
      chewing disorders, mean age of 42.38 +/- 9.36 months; Group II: 83 children with
      cerebral palsy who have chewing disorders, mean age of 39.09 +/- 22.95 months)
      using KCPS. The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used
      for criterion validity. The KCPS steps arranged between 0-4 were found to be
      necessary. The content validity index was 0.885. The KCPS levels were found to be
      different between groups I and II (chi(2) = 123.286, P < 0.001). A moderately
      strong positive correlation was found between the KCPS and the subscales of the
      BPFAS (r = 0.444-0.773, P < 0.001). An excellent positive correlation was
      detected between two swallowing therapists and between two examinations of one
      swallowing therapist (r = 0.962, P < 0.001; r = 0.990, P < 0.001, respectively).
      The KCPS is a valid, reliable, quick and clinically easy-to-use functional
      instrument for determining the level of chewing function in children. 

PMID- 27043313
TI  - Building Carbon Bridges on and between Fullerenes in Helium Nanodroplets.
AB  - We report the observation of sequential encounters of fullerenes with C atoms in
      an extremely cold environment. Experiments were performed with helium droplets at
      0.37 K doped with C60 molecules and C atoms derived from a novel, pure source of
      C atoms. Very high-resolution mass spectra revealed the formation of carbenes of
      the type C60(C:)n with n up to 6. Bridge-type bonding of the C adatoms to form
      the known dumbbell C60?C?C60 also was observed. Density functional theory
      calculations were performed that elucidated the carbene character of the C60(C:)n
      species and their structures. Mass spectra taken in the presence of water
      impurities and in separate experiments with added H2 also revealed the formation
      of the adducts C60C(n)(H2O)n and C60C(n)(H2)n probably by H-OH and H-H bond
      insertion, respectively, and nonreactivity for the dumbell. So C adatoms that
      form carbenes C60(C:)n can endow pristine C60 with a higher chemical reactivity.

PMID- 27043314
TI  - Naphthochromenes and Related Constituents from the Tubers of Sinningia
      allagophylla.
AB  - Chemical investigation of the tubers of Sinningia allagophylla led to the
      isolation of two new chromenes, (2S)-12-hydroxylapachenole (1) and (3R)-3,4
      dihydro-3-hydroxy-4-oxo-8-methoxylapachenole (2), and three new dimeric
      chromenes, allagophylldimers A-C (3-5). Thirteen known compounds, 6-methoxy-7,8
      benzocoumarin (6), lapachenole, 8-methoxylapachenole, tectoquinone, 7
      hydroxytectoquinone, dunniol, alpha-dunnione, dunnione, 8-hydroxydunnione,
      aggregatin E, cedrol, oleanolic acid, and halleridone, were also identified. 6
      Methoxy-7,8-benzocoumarin (6) has been isolated for the first time from a natural
      source. 

PMID- 27043315
TI  - Virulent Mycobacterium bovis Beijing Strain Activates the NLRP7 Inflammasome in
      THP-1 Macrophages.
AB  - Mycobacterium bovis is the causative agent of tuberculosis in a wide range of
      mammals, including humans. Macrophages are the first line of host defense. They
      secrete proinflammatory cytokines, such as interleukin-1 beta (IL-1beta), in
      response to mycobacterial infection, but the underlying mechanisms by which human
      macrophages are activated and release IL-1beta following M. bovis infection are
      poorly understood. Here we show that the 'nucleotide binding and oligomerization
      of domain-like receptor (NLR) family pyrin domain containing 7 protein' (NLRP7)
      inflammasome is involved in IL-1beta secretion and caspase-1 activation induced
      by M. bovis infection in THP-1 macrophages. NLRP7 inflammasome activation
      promotes the induction of pyroptosis as well as the expression of tumor necrosis
      factor alpha (TNF-alpha), Chemokine (C-C motif) ligand 3 (CCL3) and IL-1beta
      mRNAs. Thus, the NLRP7 inflammasome contributes to IL-1beta secretion and
      induction of pyroptosis in response to M. bovis infection in THP-1 macrophages. 

PMID- 27043316
TI  - CD34 expression modulates tube-forming capacity and barrier properties of
      peripheral blood-derived endothelial colony-forming cells (ECFCs).
AB  - Endothelial colony-forming cells (ECFC) are grown from circulating CD34(+)
      progenitors present in adult peripheral blood, but during in vitro expansion part
      of the cells lose CD34. To evaluate whether the regulation of CD34 characterizes
      the angiogenic phenotypical features of PB-ECFCs, we investigated the properties
      of CD34(+) and CD34(-) ECFCs with respect to their ability to form capillary-like
      tubes in 3D fibrin matrices, tip-cell gene expression, and barrier integrity.
      Selection of CD34(+) and CD34(-) ECFCs from subcultured ECFCs was accomplished by
      magnetic sorting (FACS: CD34(+): 95 % pos; CD34(-): 99 % neg). Both fractions
      proliferated at same rate, while CD34(+) ECFCs exhibited higher tube-forming
      capacity and tip-cell gene expression than CD3(4-) cells. However, during cell
      culture CD34(-) cells re-expressed CD34. Cell-seeding density, cell-cell contact
      formation, and serum supplements modulated CD34 expression. CD34 expression in
      ECFCs was strongly suppressed by newborn calf serum. Stimulation with FGF-2,
      VEGF, or HGF prepared in medium supplemented with 3 % albumin did not change CD34
      mRNA or surface expression. Silencing of CD34 with siRNA resulted in
      strengthening of cell-cell contacts and increased barrier function of ECFC
      monolayers as measured by ECIS. Furthermore, CD34 siRNA reduced tube formation by
      ECFC, but did not affect tip-cell gene expression. These findings demonstrate
      that CD34(+) and CD34(-) cells are different phenotypes of similar cells and that
      CD34 (1) can be regulated in ECFC; (2) is positively involved in capillary-like
      sprout formation; (3) is associated but not causally related to tip-cell gene
      expression; and (4) can affect endothelial barrier function.

PMID- 27043317
TI  - Evaluation of a Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence
      Guided Surgery of Hypoxic Tumors.
AB  - Proof-of-principle studies in ovarian, lung, and brain cancer patients have shown
      that fluorescence-guided surgery can enable removal of otherwise undetectable
      malignant lesions, decrease the number of cancer-positive margins, and permit
      identification of disease-containing lymph nodes that would have normally evaded
      resection. Unfortunately, the current arsenal of tumor-targeted fluorescent dyes
      does not permit identification of all cancers, raising the need to design new
      tumor-specific fluorescent dyes to illuminate the currently undetectable cancers.
      In an effort to design a more universal fluorescent cancer imaging agent, we have
      undertaken to synthesize a fluorophore that could label all hypoxic regions of
      tumors. We report here the synthesis, in vitro binding, and in vivo imaging of a
      near-infrared (NIR) fluorescent dye that is targeted to carbonic anhydrase IX (CA
      IX), i.e., a widely accepted marker of hypoxic tissues. The low molecular weight
      NIR probe, named Hypoxyfluor, is shown to bind CA IX with high affinity and
      accumulate rapidly and selectively in CA IX positive tumors. Because nearly all
      human cancers contain hypoxic regions that express CA IX abundantly, this NIR
      probe should facilitate surgical resection of a wide variety of solid tumors.

PMID- 27043319
TI  - Direct calculation of the X-ray structure factor of ionic liquids.
AB  - A conceptually simple and computationally efficient direct method to calculate
      the total X-ray structure factor of ionic liquids from molecular simulations is
      advocated to be complementary to the popular Fourier transform (FT) method. The
      validity of the direct method is well formulated and established by comparison
      with FT results. The effectiveness is demonstrated through versatile partition
      schemes using tetradecyltrihexylphosphonium bis(trifluoromethylsulfonyl)amide
      P14,666 Tf2N as a model system. Three characteristic intermolecular peaks were
      observed below 2 A(-1), consistent with experimental X-ray measurements. The
      prepeak corresponds to the polarity alternation leading to structural
      heterogeneity and the intermediate shoulder is due to the ubiquitous charge
      ordering of the ionic liquid. The intense peak is mainly attributed to the
      adjacent contact of apolar cationic tails. The cationic head-anion correlation
      function is found to be a unique signature for all three characteristic length
      scales even if a certain peak is concealed by fortuitous cancellation in the X
      ray structure factor. The proposed direct formulation can be readily extended to
      neutron scattering experiments. 

PMID- 27043320
TI  - Outcome of intravitreal dexamethasone implant for the treatment of ranibizumab
      resistant macular edema secondary to retinal vein occlusion.
AB  - To assess the effect of intravitreal dexamethasone implant (Ozurdex) for the
      treatment of macular edema secondary to retinal vein occlusion (RVO) resistant to
      repeated intravitreal ranibizumab injection. Retrospective review of 11 patients
      (11 eyes) with ranibizumab-resistant macular edema secondary to RVO. Macular
      edema was considered refractory to ranibizumab if no change of the pattern of
      macular fluid on optical coherence tomography and no change of best-corrected
      visual acuity (BCVA) was observed after at least three consecutive monthly
      injections, excluding the loading dose. A single Ozurdex injection was performed
      and BCVA and central foveal thickness (CFT) were reviewed 2, 3, and 6 months
      after treatment. Mean BCVA improved significantly from 0.51 logarithm of the
      minimal angle of resolution (log MAR) at baseline to 0.3 log MAR (p = 0.03) at 2
      months and 0.29 log MAR (p = 0.003) at 3 months. There was no significant
      difference in the BCVA between baseline at 6 months (p = 0.62). Mean CFT reduced
      significantly from 538 um at baseline to 281 um at 2 months (p = 0.00003), 281 um
      at 3 months (p = 0.00003), and 445 um at 6 months (p = 0.03). Treatment with
      Ozurdex results in improvement of BCVA and reduction of CFT in patients with
      ranibizumab refractory macular edema due to RVO at 3 months. However, it seems
      that the visual acuity gain may not last up to 6 months, so that a re-injection
      before this time point could be considered.

PMID- 27043321
TI  - Transcriptome analysis reveals physiological characteristics required for
      magnetosome formation in Magnetospirillum gryphiswaldense MSR-1.
AB  - Magnetosome synthesis ability of Magnetospirillum gryphiswaldense MSR-1 in an
      autofermentor can be precisely controlled through strict control of dissolved
      oxygen concentration. In this study, using transcriptome data we discovered gene
      transcriptional differences and compared physiological characteristics of MSR-1
      cells cultured under aerobic (high-oxygen) and micro-aerobic (low-oxygen)
      conditions. The results showed that 77 genes were up-regulated and 95 genes were
      down-regulated significantly under micro-aerobic situation. These genes were
      involved primarily in the categories of cell metabolism, transport, regulation
      and unknown-function proteins. The nutrient transport and physiological
      metabolism were slowed down under micro-aerobic condition, whereas dissimilatory
      denitrification pathways were activated and it may supplemental energy was made
      available for magnetosome synthesis. The result suggested that the genes of
      magnetosome membrane proteins (Mam and Mms) are not directly regulated by oxygen
      level, or are constitutively expressed. A proposed regulatory network of
      differentially expressed genes reflects the complexity of physiological
      metabolism in MSR-1, and suggests that some yet-unknown functional proteins play
      important roles such as ferric iron uptake and transport during magnetosome
      synthesis. The transcriptome data provides a holistic view of the responses of
      MSR-1 cells to differing oxygen levels. This approach will give new insights into
      general principles of magnetosome formation.

PMID- 27043323
TI  - Longitudinal Relations Among Parental Monitoring Strategies, Knowledge, and
      Adolescent Delinquency in a Racially Diverse At-Risk Sample.
AB  - Parents raising youth in high-risk communities at times rely on active, involved
      monitoring strategies in order to increase both knowledge about youth activities
      and the likelihood that adolescents will abstain from problem behavior. Key
      monitoring literature suggests that some of these active monitoring strategies
      predict increases in adolescent problem behavior rather than protect against it.
      However, this literature has studied racially homogenous, low-risk samples,
      raising questions about generalizability. With a diverse sample of youth (N =
      753; 58% male; 46% Black) and families living in high-risk neighborhoods,
      bidirectional longitudinal relations were examined among three aspects of
      monitoring (parental discussions of daily activities, parental curfew rules, and
      adolescent communication with parents), parental knowledge, and youth
      delinquency. Parental discussion of daily activities was the strongest predictor
      of parental knowledge, which negatively predicted delinquency. However, these
      aspects of monitoring did not predict later delinquency. Findings were consistent
      across gender and race/urbanicity. Results highlight the importance of active and
      involved parental monitoring strategies in contexts where they are most needed.

PMID- 27043322
TI  - State-of-the-Art Metabolic Toxicity Screening and Pathway Evaluation.
AB  - Routine in vitro bioassays and animal toxicity studies of drug and environmental
      chemical candidates fail to reveal toxicity in ~30% of cases. This Feature
      article addresses research on new approaches to in vitro toxicity testing as well
      as our own efforts to produce high-throughput genotoxicity arrays and LC-MS/MS
      approaches to reveal possible chemical pathways of toxicity.

PMID- 27043324
TI  - Surgical margins in head and neck squamous cell carcinoma: Effect of heat
      artifact on immunohistochemistry as a future tool for assessment.
AB  - BACKGROUND: Margins in head and neck squamous cell carcinoma (HNSCC) are
      determined by morphological changes assessed via hematoxylin-eosin staining.
      Physiological changes may not be detected by this technique. The purpose of this
      study was to determine if a protein biomarker, laminin-332gamma2, overexpressed
      in cancer cells at the invasive front in HNSCC, remains unaffected by heat
      produced during resection, supporting a role for immunohistochemistry assessment
      of margins. METHODS: Archived tissue blocks from glottic squamous cell carcinomas
      (SCCs) resected by CO2 laser likely to contain both cancer cells and artifact
      were identified; 129-paired slides were obtained. One slide of each pair was
      stained with hematoxylin-eosin; the second stained for laminin-332gamma2. The
      presence of cancer cells, artifact, and positive laminin-332gamma2 staining was
      recorded. Twenty-seven pairs met the inclusion criteria. RESULTS:
      Immunohistochemistry staining of laminin-332gamma is preserved in presence of
      heat artifact. CONCLUSION: This study supports use of immunohistochemistry to
      assess margins. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1401-1406, 2016.

PMID- 27043325
TI  - Enthalpy of Formation and O-H Bond Dissociation Enthalpy of Phenol: Inconsistency
      between Theory and Experiment.
AB  - Gas-phase O-H homolytic bond dissociation enthalpy in phenol, DH298 degrees
      (C6H5O-H), is still disputed, despite a large number of experimental and
      computational studies. In estimating this value, the experimental enthalpy of
      formation of phenol, DeltafH298 degrees (C6H5OH, g) = -96.4 +/- 0.6 kJ/mol (Cox,
      J. D. Pure Appl. Chem. 1961, 2, 125-128), is often used assuming high accuracy of
      the experimental value. In the present work a substantially less negative value
      of DeltafH298 degrees (C6H5OH, g) = -91.8 +/- 2.5 kJ/mol was calculated combining
      G4 theory with an isodesmic reaction approach. A benchmark quality of this result
      was achieved by using a large number of reliable reference species in isodesmic
      reaction calculations. Among these are the most accurate DeltafH298 degrees 
      values currently available from the Active Thermochemical Tables (ATcT) for 36
      species (neutral molecules, radicals, and ions), anisole with recently reassessed
      enthalpy of formation, and 13 substituted phenols. The internal consistency of
      the calculated DeltafH298 degrees (C6H5OH, g) value with the experimental
      enthalpies of formation of more than 50 reference species suggests that the
      reported experimental enthalpy of formation of phenol is in error. Taking into
      account that the enthalpy of formation of phenol has not been investigated
      experimentally since 1961, the new measurements would be extremely valuable.
      Using the accurate enthalpies of formation of C6H5OH and C6H5O* calculated in the
      present work, we obtained DH298 degrees (C6H5O-H) = 369.6 +/- 4.0 kJ/mol. This
      value is in satisfactory agreement with that determined from the most precise
      experimental measurement.

PMID- 27043326
TI  - Alcohol-related diagnoses and increased mortality in acute myocardial infarction
      patients: An analysis of the nationwide inpatient sample.
AB  - BACKGROUND: Moderate alcohol consumption has been associated with lower risk of
      coronary heart disease death, but heavy alcohol consumption may increase risk.
      OBJECTIVE: We sought to determine the association of alcohol-related diagnoses
      with in-hospital mortality in patients with acute myocardial infarction (AMI).
      DESIGN/SETTING/PATIENTS: Discharge data collected from all admissions recorded in
      the Nationwide Inpatient Sample (NIS) database from 2011. A cross-sectional
      analysis was performed using regression methods appropriate for the NIS sample
      design. MEASURES: The outcome measures were in-hospital mortality, length of
      stay, and cardiac procedures. RESULTS: AMI accounted for 610,963 (1.9%) of adult
      in-patient admissions, with an in-hospital mortality rate of 5.3%. Alcohol
      related diagnoses were associated with increased mortality in AMI patients after
      controlling for factors associated with alcoholism including age, sex, liver
      disease, hypertension, diabetes, renal failure, peripheral vascular disease,
      arrhythmias, drug abuse, gastrointestinal bleed, and smoking (adjusted odds ratio
      [OR]: 1.5, 95% confidence interval [CI]: 1.2-1.7, P < 0.001). This association
      was significant in both ST-elevation myocardial infarction patients (adjusted OR:
      1.7, 95% CI: 1.4-2.2, P < 0.001) and non-ST-elevation myocardial infarction
      patients (adjusted OR: 1.3, 95% CI: 1.0-1.7, P = 0.025). Chronic alcohol-related
      diagnoses were significantly associated with death, but acute alcohol effects (as
      estimated by withdrawal and intoxication) were not associated. CONCLUSION:
      Chronic alcohol-related diagnoses were associated with a modest increase in the
      risk for death in individuals presenting with AMI. This risk was not accounted
      for by common alcohol-related comorbidities. As a component of global efforts to
      limit hospital deaths from AMI, future research should identify the factors
      underlying this association. Journal of Hospital Medicine 2016;11:563-567. (c)
      2016 Society of Hospital Medicine.

PMID- 27043327
TI  - Telemonitoring of CPAP therapy may save nursing time.
AB  - PURPOSE: Telemonitoring might enhance continuous positive airway pressure (CPAP)
      adherence and save nursing time at the commencement of CPAP therapy. We tested
      wireless telemonitoring (ResTraxx Online System(r), ResMed) during the
      habituation phase of the CPAP therapy in obstructive sleep apnea syndrome (OSAS).
      METHODS: In total, 111 consecutive OSAS patients were enrolled. After CPAP
      titration, patients were followed with the telemonitoring (TM, N = 50) or the
      usual care (UC, N = 61). The TM group used fixed pressure CPAP device with and
      the UC group similar device without wireless telemonitoring. Patients and study
      nurses were unblinded. The evaluated end-points were hours of CPAP use >4 h/day,
      mask leak <0.4 L/s, and AHI <5/h. Nursing time including extra phone calls,
      visits, and telemonitoring time was recorded during the habituation phase. CPAP
      adherence was controlled in the beginning and at the end of the habituation phase
      and after 1-year of use. RESULTS: TM and UC groups did not differ in terms of
      patient characteristics. The average length of the habituation phase was 4 weeks
      in the TM group and fixed 3 months in the UC group. Median nursing time was 39
      min (range 12-132 min) in the TM group and shorter compared to that of 58 min
      (range 40-180 min) (p < 0.001) per patient in the UC group. Both treatment groups
      had high CPAP usage hours (>4 h/day) and the change in usage at the end of the
      habituation phase did not differ between the groups (p = 0.39). Patients in both
      groups were equally satisfied with the treatment protocol. CPAP adherence (6.4 h
      in TM vs. 6.1 h in UC group, p = 0.63) and residual AHI (1.3 in TM vs. 3.2 in UC
      group, p = 0.04) were good in both groups at 1-year follow-up. CONCLUSIONS:
      Wireless telemonitoring of CPAP treatment could be relevant in closing the gap
      between the increasing demand and available health-care resources. It may save
      nursing time without compromising short- or long-term effectiveness of CPAP
      treatment in OSAS.

PMID- 27043328
TI  - Varenicline for smoking cessation and reduction in people with severe mental
      illnesses: systematic review and meta-analysis.
AB  - AIMS: To determine the effectiveness and safety of varenicline in treating
      tobacco dependence in patients with severe mental illness. DESIGN: A systematic
      review and meta-analysis of randomised controlled trials that compared
      varenicline with a placebo or an alternative intervention for smoking cessation
      or reduction. SETTING: Both in- and out-patient settings in any country.
      PARTICIPANTS: Adult patients aged 18 years and over with any type of severe
      mental illness. The systematic review included eight studies comprising 398
      participants. MEASURES: Primary outcome measures were (1) smoking cessation, (2)
      smoking reduction measured by changes in the number of cigarettes smoked per day
      and (3) number of psychiatric adverse events, which were collected at the end of
      treatment. FINDINGS: The random-effect pooled estimates from the five studies
      that reported smoking-related outcomes found that varenicline is statistically
      superior to placebo in smoking cessation [risk ratios 4.33; 95% confidence
      interval (CI) = 1.96-9.56], and smoking reduction was higher in varenicline
      groups (mean reduced daily cigarettes was 6.39; 95% CI = 2.22-10.56). There is no
      significant difference regarding neuropsychiatric and other adverse events.
      CONCLUSIONS: Varenicline appears to be significantly more effective than placebo
      in assisting with smoking cessation and reduction in people with severe mental
      illness. There appears to be no clear evidence that varenicline was associated
      with an increased risk of neuropsychiatric or other adverse events compared with
      placebo.

PMID- 27043329
TI  - Breastmilk fatty acids in relation to sensitization - the ALADDIN birth cohort.
AB  - BACKGROUND: Breastmilk fatty acids (FAs) have been associated with childhood
      allergic disease. Children of families with an anthroposophic lifestyle have a
      low prevalence of sensitization compared to reference groups. This study aimed to
      investigate whether the lower prevalence of sensitization among these children
      can be explained by the differences in breastmilk FA composition. METHODS: The
      prospective birth cohort ALADDIN included 330 children from anthroposophic,
      partly anthroposophic and nonanthroposophic families recruited between 2004 and
      2007 in Sweden. In total, 245 breastmilk samples, collected at 2 months of age,
      were analysed for FA composition. Allergen-specific IgE levels against seven
      common allergens were measured in the blood samples at the ages of 6, 12 and 24
      months. Data were analysed longitudinally using generalized estimating equations.
      RESULTS: An inverse association was observed between total concentration of omega
      3 PUFA in breastmilk and sensitization in the child up to 24 months of age
      (highest vs lowest quartile, RRadj 0. 49, 95% CI 0.23-1.05, P for trend 0.024).
      No associations were observed between omega-6 PUFAs or ruminant FAs and
      sensitization. Overall, we observed 56% lower risks of sensitization among the
      anthroposophic group compared to the nonanthroposophic group (RRadj 0.44, 95% CI
      0.21-0.90). This association remained largely unchanged when breastmilk omega-3
      PUFA was included in the model. CONCLUSION: Our results indicate that a higher
      concentration of omega-3 PUFAs in breastmilk may be associated with a reduced
      risk of sensitization up to 24 months of age; however, this did not explain the
      lower risk of sensitization among children of anthroposophic families.

PMID- 27043330
TI  - Cost and Budget Impact Analysis of an Accurate Intraoperative Sentinel Lymph Node
      Diagnosis for Breast Cancer Metastasis.
AB  - BACKGROUND: Conventional intraoperative sentinel lymph node biopsy (SLNB) in
      breast cancer (BC) has limitations in establishing a definitive diagnosis of
      metastasis intraoperatively, leading to an unnecessary second operation. The one
      step nucleic amplification assay (OSNA) provides accurate intraoperative
      diagnosis and avoids further testing. Only five articles have researched the cost
      and cost effectiveness of this diagnostic tool, although many hospitals have
      adopted it, and economic evaluation is needed for budget holders. OBJECTIVE: We
      aimed to measure the budget impact in Japanese BC patients after the introduction
      of OSNA, and assess the certainty of the results. METHODS: Budget impact analysis
      of OSNA on Japanese healthcare expenditure from 2015 to 2020. Local governments,
      society-managed health insurers, and Japan health insurance associations were the
      budget holders. In order to assess the cost gap between the gold standard (GS)
      and OSNA in intraoperative SLNB, a two-scenario comparative model that was
      structured using the clinical pathway of a BC patient group who received SLNB was
      applied. Clinical practice guidelines for BC were cited for cost estimation.
      RESULTS: The total estimated cost of all BC patients diagnosed by GS was
      US$1,023,313,850. The budget impact of OSNA in total health expenditure was 
      US$24,413,153 (-US$346 per patient). Two-way sensitivity analysis between
      survival rate (SR) of the GS and OSNA was performed by illustrating a cost-saving
      threshold: y ? 1.14x - 0.16 in positive patients, and y ? 0.96x + 0.029 in
      negative patients (x = SR-GS, y = SR-OSNA). Base inputs of the variables in these
      formulas demonstrated a cost saving. CONCLUSION: OSNA reduces healthcare costs,
      as confirmed by sensitivity analysis.

PMID- 27043331
TI  - The Impact of Perceived Flood Exposure on Flood-Risk Perception: The Role of
      Distance.
AB  - Natural hazards, such as major flood events, are occurring with increasing
      frequency and inflicting increasing levels of financial damages upon affected
      communities. The experience of such major flood events has brought about a
      significant change in attitudes to flood-risk management, with a shift away from
      built engineering solutions alone towards a more multifaceted approach. Europe's
      experience with damaging flood episodes provided the impetus for the introduction
      of the European Floods Directive, requiring the establishment of flood-risk
      management plans at the river-basin scale. The effectiveness of such plans,
      focusing on prevention, protection, and preparedness, is dependent on adequate
      flood awareness and preparedness, and this is related to perception of flood
      risk. This is an important factor in the design and assessment of flood-risk
      management. Whilst there is a modern body of literature exploring flood
      perception issues, there have been few examples that explore its spatial
      manifestations. Previous literature has examined perceived and real distance to a
      hazard source (such as a river, nuclear facility, landfill, or incinerator,
      etc.), whereas this article advances the literature by including an objectively
      assessed measure of distance to a perceived flood zone, using a cognitive mapping
      methodology. The article finds that distance to the perceived flood zone
      (perceived flood exposure) is a crucial factor in determining flood-risk
      perception, both the cognitive and affective components. Furthermore, we find an
      interesting phenomenon of misperception among respondents. The article concludes
      by discussing the implications for flood-risk management.

PMID- 27043332
TI  - Cutaneous, Purpuric Painful Nodules Upon Addition of Ibrutinib to RCVP Therapy in
      a CLL Patient: A Distinctive Reaction Pattern Reflecting Iatrogenic Th2 to Th1
      Milieu Reversal.
AB  - A 70-year-old white man with stage C chronic lymphocytic leukemia who was being
      successfully treated with ibrutinib and rituximab developed bilateral, purpuric,
      painful cutaneous nodules. Biopsies of these nodules did not reveal the usual Th2
      milieu of chronic lymphocytic leukemia but instead exhibited a Th1-rich
      lymphocytic infiltrate with resultant neutrophil and granulomatous inflammation.
      The eruption resolved with drug cessation emphasizing the potential importance of
      this drug in treating conditions associated with Th2 dysregulation. 

PMID- 27043333
TI  - Idiopathic Gingival Fibromatosis: Case Report and Review of the Literature.
AB  - Gingival fibromatosis (GF) is a condition characterized by a progressive, normal
      colored enlargement of the gingiva caused by an increase in the size of
      submucosal connective tissue. Both familial and idiopathic variants of the
      condition exist. The authors present a case report of a 38-year-old African
      American man who presented with an impressive overgrowth of the maxillary and
      mandibular gingivae, subsequently diagnosed as idiopathic GF. In this report, the
      authors will review the etiologies, treatment, and clinical and histological
      findings of GF, review similar cases found in the literature, and discuss the
      differential diagnosis for diffuse gingival enlargements. 

PMID- 27043334
TI  - NRAS Status in Giant Melanocytic Nevus With Metastatic Melanoma.

PMID- 27043335
TI  - Rosacea-Like Leukemia Cutis: A Case Report.
AB  - Leukemia cutis describes the infiltration and dissemination of neoplastic
      leukemic cells into the epidermis, dermis, or subcutis, resulting in clinically
      identifiable cutaneous lesions. Depending on the type of leukemia, a wide range
      of clinical and histopathological findings may be encountered. This report
      describes a patient with a rosacea-like eruption as a unique clinical
      presentation of T-cell prolymphocytic leukemia. 

PMID- 27043336
TI  - Morpheaform Basal Cell Carcinomas With Areas of Predominantly Single-Cell Pattern
      of Infiltration: Diagnostic Utility of p63 and Cytokeratin.
AB  - BACKGROUND: Morpheaform basal cell carcinoma (BCC) is a variant of BCC
      characterized by narrow strands and nests of basaloid cells with dense sclerotic
      stroma. The histologic extent often exceeds the clinical impression, leading to
      high recurrence rates after standard excision. The authors encountered a case
      with single-cell invasion distant from the main tumor. To date a systematic
      review of single-cell infiltration in morpheaform BCC has yet to be performed.
      DESIGN: Ten morpheaform BCCs, 10 nonmorpheaform aggressive BCCs, 5 desmoplastic
      trichoepitheliomas, and 2 microcystic adnexal carcinomas were identified by
      database search and confirmed on hematoxylin and eosin. Cases were evaluated by
      hematoxylin and eosin, immunohistochemical staining for p63, and (in a subset)
      broad-spectrum cytokeratin. Single-cell pattern was defined as individual cells,
      2-cell clusters, or single-file invasion. RESULTS: Three types of single-cell
      pattern were identified: intratumoral (single cells within the main tumor mass),
      peripheral, and distant. Single cells were typically a minor component relative
      to larger tumor nodules and strands. Eight of the 10 cases of morpheaform BCC
      demonstrated areas of single-cell pattern: 3 intratumoral, 3 peripheral, and 2
      with distant spread (0.75 and 1.0 mm from the main tumor). Eight of the 10
      aggressive BCC demonstrated a peripheral single-cell pattern. Rare intratumoral
      single cells were identified in 3/5 desmoplastic trichoepitheliomas and 1/2
      microcystic adnexal carcinomas. CONCLUSION: Single-cell pattern is frequently a
      component of morpheaform BCC. Tumor cells at a significant distance from the main
      component were unique to morpheaform BCC. Thus, when evaluating margins for
      morpheaform BCC, increased caution is recommended, and immunohistochemical stains
      for p63 or cytokeratins may be helpful.

PMID- 27043337
TI  - Spitz Nevus Intermingling With a Hemangioma.
AB  - We report on a Spitz nevus intermingling with a hemangioma in the same biopsy
      from the right thigh of a 10-year-old boy. The hemangioma was made of dilated
      vessels in superficial areas but of narrow and angulated vessels in the deep and
      lateral zones. The Spitz nevus was typical, showing maturation, and no worrisome
      cytological features. The immunohistochemical study demonstrated expression by
      the vascular component of CD31, CD34, factor VIII-related antigen, and Wilms
      tumor 1, whereas the vessels did not express D2-40 human herpes virus 8 or
      glucose transporter-1. The melanocytic component expressed HMB-45 (weakly and
      mainly in the superficial zones), Melan-A and S-100 protein. A perivascular
      continuous layer of pericytes expressing smooth muscle actin was also evident. 

PMID- 27043338
TI  - Eruptive Disseminated Porokeratosis in a Patient With Type 2 Diabetes Mellitus.
AB  - Porokeratosis includes a group of heterogenous disorders that represents distinct
      clinical subtypes of the same genetic pattern. Although entire pathogenesis of
      porokeratosis still remains unknown, certain factors including ultraviolet
      radiation and immunosuppression are suggested to be some of the factors inducing
      this disorder. Eruptive disseminated porokeratosis is a recently described form
      of porokeratosis, which frequently occurs in the presence of immunosuppresion or
      malignancy. The authors report here a unique case with sudden onset eruptive
      disseminated porokeratosis associated with diabetes mellitus. 

PMID- 27043339
TI  - Cutaneous Osteoblastic Osteosarcoma: Report of 2 New Cases Integrated With SATB2
      Immunohistochemistry and Review of the Literature.
AB  - We report 2 cases of primary dermal osteosarcoma. The patients were an 88-year
      old man and a 72-year-old man complaining of masses occurring in the ear pavilion
      and the palm, deemed suspicious for basal cell carcinoma and metastatic colonic
      carcinoma, and were treated by resection. Microscopically, both featured a dermal
      lesion mostly composed of atypical spindle cells within a fibrous to hyaline
      matrix often showing mineralization. Osteoid material was rimmed by atypical
      tumor cells and was also associated with osteoclast-like giant cells. Tumor cells
      were positive for SATB2 and negative for markers of epithelial (low-molecular and
      high-molecular weight cytokeratins, epithelial membrane antigen, p63),
      melanocytic (S100 protein, HMB45, Melan A), and skeletal/smooth muscle
      differentiation (desmin, myogenin). No further therapy has been administered.
      Follow-up at 6 (case 1) and 8 months (case 2) was uneventful. A brief
      differential diagnosis discussing cutaneous tumors capable of showing osseous
      differentiation is summarized, along with a review of the pertinent literature.
      The specificity and sensitivity of SATB2 is also shortly addressed.

PMID- 27043340
TI  - Cutaneous Metastasis of a Mucoepidermoid Carcinoma of the Pancreas: First
      Reported Case.
AB  - BACKGROUND: Mucoepidermoid pancreatic cancer is a rare entity with only 8 cases
      reported in the literature. On review of the literature, the authors found that
      cutaneous metastases in pancreatic cancer are rare and have not been associated
      with the mucoepidermoid subtype. The authors present the first reported case of
      cutaneous metastasis in a patient with mucoepidermoid carcinoma of the pancreas.
      CASE PRESENTATION: A 50-year old white male with a metastatic invasive poorly
      differentiated mucoepidermoid carcinoma of the pancreas was found to have a slow
      growing lesion in the skin over his left upper quadrant while undergoing active
      therapy. The lesion was biopsied and the pathology was consistent with pancreatic
      origin sharing similar morphologic features when compared with the primary
      pancreactectomy specimen. CONCLUSIONS: Mucoepidermoid pancreatic cancer is an
      exceedingly rare subtype of pancreatic cancer, with very little information
      regarding its diagnosis, treatment, and patterns of metastases. Here, the authors
      present the first reported case of cutaneous metastases of mucoepidermoid
      pancreatic cancer.

PMID- 27043341
TI  - Refining the Y chromosome phylogeny with southern African sequences.
AB  - The recent availability of large-scale sequence data for the human Y chromosome
      has revolutionized analyses of and insights gained from this non-recombining,
      paternally inherited chromosome. However, the studies to date focus on Eurasian
      variation, and hence the diversity of early-diverging branches found in Africa
      has not been adequately documented. Here, we analyze over 900 kb of Y chromosome
      sequence obtained from 547 individuals from southern African Khoisan- and Bantu
      speaking populations, identifying 232 new sequences from basal haplogroups A and
      B. We identify new clades in the phylogeny, an older age for the root, and
      substantially older ages for some individual haplogroups. Furthermore, while
      haplogroup B2a is traditionally associated with the spread of Bantu speakers, we
      find that it probably also existed in Khoisan groups before the arrival of Bantu
      speakers. Finally, there is pronounced variation in branch length between major
      haplogroups; in particular, haplogroups associated with Bantu speakers have
      significantly longer branches. Technical artifacts cannot explain this branch
      length variation, which instead likely reflects aspects of the demographic
      history of Bantu speakers, such as recent population expansion and an older
      average paternal age. The influence of demographic factors on branch length
      variation has broader implications both for the human Y phylogeny and for similar
      analyses of other species. 

PMID- 27043342
TI  - High-throughput analysis of immunoglobulin G glycosylation.
AB  - INTRODUCTION: Glycosylation of immunoglobulin G (IgG) is important for its
      effector functions and was shown to be related to age, sex and disease status of
      an individual. Adding glycomic information to genome-wide association studies
      (GWAS) and large clinical trials is enabling insight into the functional
      relevance of changes in glycosylation, as well as molecular mechanisms behind
      these changes. Large-scale studies require sensitive, robust and affordable high
      throughput methodologies for glycosylation analysis, which are currently
      available in only a limited number of laboratories. AREAS COVERED: This review
      focuses on currently used high-throughput approaches for N-glycosylation analysis
      of IgG, as well as some recent advances in the areas of deglycosylation, trypsin
      digestion, labeling, purification, derivatization and automation of current
      workflows. Relevant literature was searched using the PubMed database. Expert
      commentary: Development, optimization and validation of robust, affordable and
      simple high-throughput glycosylation analysis methods is essential for discovery
      and validation of diagnostic and prognostic glycan biomarkers. Although
      significant advances in glycosylation analysis have been made in recent years,
      currently used protocols will have to be further optimized to enable subsequent
      analysis of glycosylation on all levels with the limited initial sample and in
      the minimal amount of time, which is still a challenging task.

PMID- 27043343
TI  - Sport and early osteoarthritis: the role of sport in aetiology, progression and
      treatment of knee osteoarthritis.
AB  - Sports activities are considered favourable for general health; nevertheless, a
      possible influence of sports practice on the development of early osteoarthritis
      (OA) is a cause for concern. A higher incidence of OA in knees and ankles of
      former high-impact sports players than in those of the normal population has been
      shown and it is still debatable whether the cause is either to be recognized
      generically in the higher number of injuries or in a joint overload. The
      possibility to address knee OA in its early phases may be strictly connected to
      the modification of specific extrinsic or intrinsic factors, related to the
      patient in order to save the joint from further disease progression; these
      include sport practice, equipment and load. Non-surgical therapies such as
      continuative muscles reinforce and training play a strong role in the care of
      athletes with early OA, particularly if professional. There is an overall
      agreement on the need of an early restoring of a proper meniscal, ligament and
      cartilage integrity in order to protect the knee and resume sports safely,
      whereas alignment is a point still strongly debatable especially for professional
      athletes. Remaining questions still to be answered are the risks of different
      sports in relation to one another, although an actual protective effect of low
      impact sports, such as walking, swimming or cycling, has been recognized on the
      appearance or worsening of OA, the effect of continuing or ceasing to practice a
      sport on the natural history of early OA, and even following appropriate
      treatment is still unknown. 

PMID- 27043344
TI  - Implementation of conservative treatment prior to arthroscopic subacromial
      decompression of the shoulder.
AB  - PURPOSE: The aim of the study was to investigate to what extent patients undergo
      evidence-based conservative treatment prior to arthroscopic subacromial
      decompression of the shoulder. METHODS: One hundred and twenty patients (65
      women, 55 men, median age 53.5 years (range 28-70), referred to arthroscopic
      subacromial decompression at two hospitals in Norway, were consecutively included
      in the study. The patients completed a self-administered questionnaire including
      questions concerning the quantity and nature of preoperative treatment as well as
      the QuickDASH score. They were specifically asked for the extent of evidence
      based conservative treatment, i.e. the combination of strengthening and
      stretching exercises at a minimum weekly amount and total duration. RESULTS: One
      hundred and nine patients (91 %) reported having received conservative treatment
      guided by a physiotherapist preoperatively. The patients' main reasons for not
      seeing a physiotherapist were lack of trust in the treatment (N = 7) and the
      assumption that surgery would provide faster relief of symptoms (N = 6). Of those
      visiting a physiotherapist, 80 % received specific shoulder exercises. Forty-five
      per cent did both strengthening and stretching exercises, only 32 % did the
      exercises three times per week more than 2 months, and 24 % did more than 3
      months as recommended. Seventy-six per cent of the patients who discontinued the
      prescribed exercise programme did this due to increasing pain. CONCLUSIONS: Most
      of the patients in the current study reported having visited a physiotherapist
      before surgery. However, less than half of them underwent evidence-based exercise
      treatment, and increased pain was the main reason for not completing the
      prescribed exercise treatment. The results might be of clinical relevance for
      physiotherapists treating patients with SAPS, but also for orthopaedic surgeons
      doing preoperative evaluations. LEVEL OF EVIDENCE: Case series, IV.

PMID- 27043345
TI  - Unstable simple elbow dislocations: medium-term results after non-surgical and
      surgical treatment.
AB  - PURPOSE: Determination of the appropriate treatment of unstable simple elbow
      dislocations is difficult and a topic of ongoing discussion. The aim of this
      study was to analyse the outcome and complications after surgery and conservative
      treatment, with special focus on post-traumatic joint laxity. METHODS: In this
      retrospective study, 118 consecutive patients with simple elbow dislocations
      underwent stability testing by fluoroscopy after joint reduction and were
      assigned to groups 1 (slight), 2 (moderate) or 3 (gross) depending on post
      traumatic joint laxity. All patients of group 1 underwent conservative treatment,
      and of group 3 primary ligament repair. In patients with moderate elbow laxity,
      the treatment was decided individually. All patients underwent a similar
      functional rehabilitation programme during treatment. Clinical outcome was
      determined after an average of 3.4 +/- 1.5 years using the Mayo Elbow Performance
      Score (MEPS), and treatment-associated complications and revisions were recorded.
      RESULTS: Forty-nine patients (41.5 %) were assigned to group 1, 41 patients (34.7
      %) to group 2 and 28 patients (23.7 %) to group 3. In group 2, 22 patients
      underwent ligament repair, while 19 patients were treated conservatively. On
      average, an excellent MEPS was achieved in group 1 after conservative treatment
      (MEPS 95.8 +/- 9.0), similar to results after ligament repair of grossly unstable
      elbows in group 3 (91.6 +/- 11.7). Interestingly, in group 2 conservative
      treatment was associated with a slightly lower MEPS (90.0 vs. 95.7), and
      significantly fewer patients achieved an excellent MEPS (81.8 vs. 52.6 %, p =
      0.045). Similarly, conservative treatment in group 2 was associated with a
      fivefold to sixfold risk of complications (p = 0.032) and revision surgery (p =
      0.023). CONCLUSIONS: This study supports the notion that patients with slight
      elbow laxity can be treated non-operatively, while primary surgical treatment
      should be performed in patients with moderate and gross laxity to avoid post
      traumatic sequelae and decrease revision rates. LEVEL OF EVIDENCE: Retrospective
      Cohort Study, Level III.

PMID- 27043346
TI  - Do cartilage lesions affect the clinical outcome of anterior cruciate ligament
      reconstruction? A systematic review.
AB  - PURPOSE: To document the available evidence on the influence of cartilage lesions
      on the results of anterior cruciate ligament (ACL) surgery and their management
      to optimize the final outcome. METHODS: A systematic review was performed on the
      PubMed database on articles dealing with cartilage lesions detected at the time
      of ACL reconstruction, by looking both for their influence on the clinical
      outcome and the results of their treatment. Reports on clinical, radiological, or
      second-look outcomes at any follow-up were included. Exclusion criteria were
      preclinical studies, reviews, or studies not reporting clinical, radiological, or
      second-look outcome after primary ACL reconstruction. RESULTS: Thirty-seven
      studies were included for the final analysis. Twenty-seven focused on the
      influence of cartilage lesions on clinical outcome after ACL reconstruction in
      47,837 patients. In total, 21/27 articles showed a correlation with a poorer
      outcome in terms of subjective, objective, and radiographic findings. Lesion
      location and depth influenced final results. Only 9.0 % of these defects were
      treated in the analysed studies, and only 10 manuscripts of overall low level
      evaluated the results of combined cartilage-ACL treatments. CONCLUSION: The
      majority of the literature supports the clinical relevance of cartilage lesions
      which are correlated with a poorer outcome after ACL reconstruction. Nonetheless,
      a large amount of chondral defects are actually not addressed, also considering
      the poor evidence for the benefits provided by cartilage treatments. In fact,
      only a few studies specifically focused on how to manage cartilage lesions found
      during ACL reconstruction and there is a lack of indications for the most
      appropriate treatment approach. LEVEL OF EVIDENCE: IV.

PMID- 27043347
TI  - Non-surgical treatments for the management of early osteoarthritis.
AB  - Non-surgical treatments are usually the first choice for the management of knee
      degeneration, especially in the early osteoarthritis (OA) phase when no clear
      lesions or combined abnormalities need to be addressed surgically. Early OA may
      be addressed by a wide range of non-surgical approaches, from non-pharmacological
      modalities to dietary supplements and pharmacological therapies, as well as
      physical therapies and novel biological minimally invasive procedures involving
      injections of various substances to obtain a clinical improvement and possibly a
      disease-modifying effect. Numerous pharmaceutical agents are able to provide
      clinical benefit, but no one has shown all the characteristic of an ideal
      treatment, and side effects have been reported at both systemic and local level.
      Patients and physicians should have realistic outcome goals in pharmacological
      treatment, which should be considered together with other conservative measures.
      Among these, exercise is an effective conservative approach, while physical
      therapies lack literature support. Even though a combination of these therapeutic
      options might be the most suitable strategy, there is a paucity of studies
      focusing on combining treatments, which is the most common clinical scenario.
      Further studies are needed to increase the limited evidence on non-surgical
      treatments and their combination, to optimize indications, application
      modalities, and results with particular focus on early OA. In fact, most of the
      available evidence regards established OA. Increased knowledge about degeneration
      mechanisms will help to better target the available treatments and develop new
      biological options, where preliminary results are promising, especially
      concerning early disease phases. Specific treatments aimed at improving joint
      homoeostasis, or even counteracting tissue damage by inducing regenerative
      processes, might be successful in early OA, where tissue loss and anatomical
      changes are still at very initial stages. 

PMID- 27043348
TI  - A new simulator model for knee arthroscopy procedures.
AB  - PURPOSE: Arthroscopy is currently the "gold standard" for various surgeries
      performed on the knee joint. Therefore, surgeons wishing to operate in this
      professional field should be able to perform this technique. Arthroscopic
      training, an experimental laboratory, is important for the surgeons' training,
      enabling them to increase their skills with the specific instruments and to
      become familiar with the operating techniques. The aim of this study was to
      present a new surgical simulator for training in arthroscopic procedures of the
      knee. METHODS: The Kneetrainer 1 is a simulator consisting of a type of thermo
      retractile, thermo-sensitive synthetic rubber that has texture, colour,
      consistency, and mechanical resistance that mimic many human tissues. Nine
      simulators were used, operated by seventeen expert Brazilian surgeons in knee
      surgery. The surgeons performed arthroscopy, meniscectomy, and reconstruction of
      the anterior cruciate ligament (ACL), responded to an electronic questionnaire
      with several variables, and gave an overall score on the ability of the device to
      perform realistic simulation for the above procedures. RESULTS: The ability to
      perform the procedures of meniscectomy and ACL reconstruction was considered
      adequate by 82 and 100 % of the specialists, respectively. The overall scores for
      the ability to perform realistic simulation for the procedures meniscectomy and
      reconstruction of the anterior cruciate ligament by arthroscopy were 64.7 and
      82.4 %, respectively. The simulator was therefore considered suitable for
      practical application with novice surgeons. CONCLUSION: The Kneetrainer 1
      simulator was assessed as an effective tool for recreating accurate arthroscopic
      knee procedures. In addition, the simulator may be effective as a means of honing
      the skills of novice surgeons. Future investigations should be performed to
      validate the reliability of the simulator. LEVEL OF EVIDENCE: IV.

PMID- 27043349
TI  - Gastrointestinal: Ultrasound-guided iatrogenic hydrothorax to permit drainage of
      a postoperative left subdiaphragmatic abscess.

PMID- 27043350
TI  - Expression of the TRPM6 in mouse placental trophoblasts; potential role in
      maternal-fetal calcium transport.
AB  - The placenta is required to transport calcium (Ca2+) from mother to fetus during
      fetal bone mineralization. In an attempt to clarify the molecular basis of Ca2+
      entry for this transport, we identified TRPM6 as a candidate for apical Ca2+
      entry pathway. TRPM6 mRNA increased during the last 4 days of pregnancy,
      coinciding with fetal bone mineralization in mice. TRPM6 mRNA and protein was
      localized in the trophoblasts in labyrinth where the maternal-fetal Ca2+
      transport occurs. In patch-clamp recordings, we observed TRPM6/TRPM7-like
      currents in mouse trophoblasts after starting fetal bone mineralization but not
      before mineralization. Plasma membrane Ca2+ permeability was significantly
      increased in TRPM6/TRPM7 expressed HEK293 cells under physiological Mg2+ and ATP
      concentration but not in TRPM6 or TRPM7 homomer-expressing cells. These results
      suggest that TRPM6 is functionally expressed in mouse placental trophoblasts,
      implicating in maternal-fetal Ca2+ transport likely with TRPM7, which might
      enable to sustain fetal bone mineralization.

PMID- 27043351
TI  - Characteristics of Hyperautofluorescent Choroidal Vessels within the Macular
      Atrophic Area Using Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: The aim of this study was to clarify the characteristic findings in
      patients with geographic atrophy with or without hyperautofluorescent choroidal
      vessels within macular atrophic areas on short-wavelength fundus autofluorescence
      imaging. PROCEDURES: Sixty-seven eyes of 43 consecutive patients with macular
      atrophic areas were divided into groups with (group 1) and without (group 2)
      hyperautofluorescent choroidal vessels on fundus autofluorescence imaging and
      then retrospectively studied using spectral-domain optical coherence tomography.
      RESULTS: In group 1 (n = 21), the average subfoveal choroidal thickness was 61.5
      +/- 20.1 MUm, and the average foveal retinal thickness was 93.0 +/- 51.3 MUm. On
      the other hand, in group 2 (n = 46), the average subfoveal choroidal thickness
      was 200.7 +/- 83.1 MUm, and the average foveal retinal thickness was 109.2 +/-
      58.5 MUm. Although retinal thickness did not differ significantly between the two
      groups (p = 0.28), the difference in choroidal thickness was statistically
      significant (p < 0.001). CONCLUSIONS: Choroidal thinning might contribute to the
      hyperautofluorescence of choroidal vessels.

PMID- 27043352
TI  - Reproducibility of three different cardiac T2 -mapping sequences at 1.5T.
AB  - PURPOSE: To elucidate the impact of technical and intraindividual reproducibility
      on the overall variability of myocardial T2 relaxation times. MATERIALS AND
      METHODS: Thirty healthy volunteers were examined three times (day 1
      morning/evening, evening after 2-3 weeks) at 1.5T. During each examination three
      different T2 -mapping sequences were acquired twice at three slices in short axis
      view: multi-echo-spin-echo (MESE), T2 -prepared balanced steady-state free
      precession (SSFP) (T2 prep), and gradient-spin-echo with and without fat
      saturation (GraSE/GraSEFS ). Repeated measurements were performed for T2 prep and
      GraSE. Segmented T2 -maps were generated for each slice according to the American
      Heart Association (AHA) 16-segment model. RESULTS: The coefficients of variation
      and intraclass correlation coefficients for intraobserver variability were: 1.3%
      and 0.89 for T2 prep, 1.5% and 0.93 for GraSE, 3.1% and 0.83 for MESE; and for
      interobserver variability: 3.3% and 0.66 for T2 prep, 2.0% and 0.83 for GraSE,
      3.6% and 0.77 for MESE. No systematic difference of T2 times was observed due to
      diurnal effects and on long-term analysis using one-way analysis of variance
      (ANOVA) with Tukey-type multiple comparisons (morning vs. evening scan for T2
      prep: 52.5 +/- 2.4 vs. 51.7 +/- 2.7 msec, P = 0.119; for GraSE: 58.6 +/- 4.0 vs.
      58.5 +/- 3.8 msec, P = 0.984; for GraSEFS 57.1 +/- 3.2 vs. 57.2 +/- 3.9 msec, P =
      0.998, and for MESE: 53.8 +/- 2.7 vs. 53.3 +/- 3.3 msec, P = 0.541; scans between
      weeks for T2 prep: 51.7 +/- 2.7 vs. 51.4 +/- 2.4 msec, P = 0.873; for GraSE: 58.5
      +/- 3.8 vs. 58.1 +/- 3.4 msec, P = 0.736; for GraSEFS : 57.2 +/- 3.9 vs. 57.0 +/-
      4.6 msec, P = 0.964, and for MESE: 53.3 +/- 3.3 vs. 53.4 +/- 2.4 msec, P =
      0.970). ANOVA components, however, demonstrated a greater variance of T2 times
      over multiple timepoints than for repeated measurements within the same scan
      (variance components of the model fit for intraday variance vs. repeated
      measurements: T2 prep 2.22 vs. 1.36, GraSE 3.76 vs. 2.09, GraSEFS 3.96 vs. 1.58,
      MESE 1.86; and for interweeks variance vs. repeated measurements: T2 prep 2.21
      vs. 0.80, GraSE 3.20 vs. 2.10, GraSEFS 8.82 vs. 1.18, and MESE 4.49). CONCLUSION:
      Technical reproducibility and intra- and interobserver agreement of myocardial T2
      relaxation times are excellent and intraindividual variation over time is small.
      Therefore, we consider subject-related factors to explain most of the
      interindividual variability of myocardial T2 times reported in previous studies.
      The acknowledgment of this subject-related, biological variability may be
      important for the future diagnostic value of T2 -mapping. J. Magn. Reson. Imaging
      2016;44:1168-1178.

PMID- 27043353
TI  - Effects of full-neck volumetric-modulated arc therapy vs split-field intensity
      modulated head and neck radiation therapy on low neck targets and structures.
AB  - OBJECTIVE: While split-field intensity-modulated radiation therapy (SF-IMRT)
      decreases dose to low neck (LAN) structures such as the glottic larynx compared
      with full-neck intensity-modulated radiation therapy (IMRT), it is unknown
      whether SF-IMRT affords superior dose avoidance to organs than whole neck-field
      volumetric-modulated arc therapy (WF-VMAT). METHODS: 10 patients treated
      definitively with radiation for oropharyngeal, oral cavity or nasopharyngeal
      carcinoma were compared. Only patients ideally suited for SF-IMRT plans were
      included. The glottic larynx, supraglottic larynx, arytenoids, pharyngeal
      constrictors, oesophagus, brachial plexus and target volume coverage in the LAN
      were compared between WF-VMAT and SF-IMRT. RESULTS: Volumetric-modulated arc
      therapy (VMAT) yielded statistically significant decreases in maximum dose to the
      arytenoids and mean dose to the oesophagus. There was no difference in dose to
      the glottic larynx, supraglottic larynx, pharyngeal constrictors and brachial
      plexus. WF-VMAT led to improved coverage to 50/2 Gy fraction equivalent in LAN
      compared with SF-IMRT using an anteroposterior (AP) LAN field but no difference
      to the 60/2 Gy fraction equivalent between SF-IMRT and WF-VMAT using AP/posterior
      anterior LAN boost. CONCLUSION: WF-VMAT affords equivalent glottic and
      supraglottic larynx dose and lower dose to the arytenoids and oesophagus. WF-VMAT
      better covers most LAN target structures. Given these findings as well as
      concerns with matchline cold spots or hotspots with SF-IMRT, patients requiring
      comprehensive elective nodal irradiation should typically be treated with WF
      VMAT. ADVANCES IN KNOWLEDGE: SF-IMRT for larynx sparing has better dosimetric
      results to normal structures than whole-neck IMRT, but with increased matchline
      recurrence risk. We show dosimetric equivalence or superiority of WF-VMAT
      compared with SF-IMRT.

PMID- 27043354
TI  - Phosphorus removal from wastewater by field-scale fortified filter beds during a
      one-year study.
AB  - Due to low availability of alternative technologies, rural communities are unable
      to comply with national wastewater discharge limits. This study tested the
      effectiveness of filter bed fortification with biochar on phosphorus removal.
      Water-tight down-flow beds of sand and gas concrete, constructed alongside a
      reference sand bed (all 0.8 m deep and 0.75 m(2) surface area), were topped with
      a 0.2 m biochar layer. Pre-treated domestic wastewater with mean concentrations
      of 6.4 mg/L [Formula: see text] and 142.6 NTU, was infiltrated at 4 cm/d
      hydraulic loading rate. Ultimately, the biochar-sand was relatively outstanding
      in turbidity reduction, achieving <5 NTU. The biochar-gas concrete exhibited
      superior performance in [Formula: see text] removal, trapping 32.3 g (40.2%),
      compared with 20.5 g (25.6%) and 15.5 g (19.3%) by biochar-sand and reference bed
      respectively. However, statistical analysis revealed a weak correlation between
      pH and biochar-gas concrete removal efficiency (r(2 )= 0.2). The relationship was
      stronger for biochar-sand [Formula: see text] (r(2 )= 0.5) than reference (r(2 )=
      0.4) bed. Paired samples t-tests showed that incorporating biochar into the sand
      bed significantly (p = .04) improved its [Formula: see text] removal efficiency.
      In conclusion, sand bed fortification with biochar could be an important measure
      for improving P removal and wastewater clarification efficiency. 

PMID- 27043355
TI  - Assessing the potential of pharmaceuticals and their transformation products to
      cause mutagenic effects: Implications for gene expression profiling.
AB  - The selection and prioritization of pharmaceuticals and their transformation
      products for evaluating effects on the environment and human health is a
      challenging task. One common approach is based on compounds (e.g., mixture
      composition, concentrations), and another on biology (e.g., relevant endpoint,
      biological organizational level). Both of these approaches often resemble a
      Lernaean Hydra-they can create more questions than answers. The present study
      embraces this complexity, providing an integrated approach toward assessing the
      potential effects of transformation products of pharmaceuticals by means of
      mutagenicity, estrogenicity, and differences in the gene expression profiles.
      Mutagenicity using the tk kinase assay was applied to assess a list of 11
      priority pharmaceuticals, namely, atenolol, azithromycin, carbamazepine,
      diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol,
      sulfamethoxazole, and trimethoprim. The most mutagenic compounds were found to be
      beta-blockers. In parallel, the photolabile pharmaceuticals were assessed for
      their mixture effects on mutagenicity (tk assay), estrogenicity (T47D- KBluc
      assay), and gene expression (microarrays). Interestingly, the mixtures were
      mutagenic at the ug/L level, indicating a synergistic effect. None of the
      photolysed mixtures were statistically significantly estrogenic. Gene expression
      profiling revealed effects related mainly to certain pathways, those of the p53
      gene, mitogen-activated protein kinase, alanine, aspartate, and glutamate
      metabolism, and translation-related (spliceosome). Fourteen phototransformation
      products are proposed based on the m/z values found through ultra-performance
      liquid chromatography-tandem mass spectrometry analysis. The transformation
      routes of the photolysed mixtures indicate a strong similarity with those
      obtained for each pharmaceutical separately. This finding reinforces the view
      that transformation products are to be expected in naturally occurring mixtures.
      Environ Toxicol Chem 2016;35:2753-2764. (c) 2016 SETAC.

PMID- 27043356
TI  - Protective role of R381Q (rs11209026) polymorphism in IL-23R gene in immune
      mediated diseases: A comprehensive review.
AB  - Interleukin-23 (IL-23) is a regulator of cellular immune responses involved in
      controlling infection and autoimmune diseases. Strong evidence has shown that IL
      23 plays a role in the maintenance of immune responses by influencing the
      proliferation and survival of IL-17-producing T-helper (TH)-17 cells. The
      critical role of the IL-23/TH17 axis in immune-mediated diseases has emerged from
      different studies. It has also been seen that polymorphisms in the IL-23 receptor
      (IL-23R) gene might influence IL-23 responses. Interestingly, a functional single
      nucleotide polymorphism (SNP) in the IL-23 receptor gene (IL-23R; rs11209026,
      1142 G wild-type A reduced function, Arg381Gln, R381Q) seems to confer a measure
      of protection against development of inflammatory bowel disease (IBD; Crohn's
      disease, ulcerative colitis), ankylosing spondylitis, rheumatoid arthritis,
      psoriasis, thyroiditis, recurrent spontaneous abortion and asthma, suggesting
      that a perturbation in the IL-23 signaling pathway is likely to be relevant to
      the pathophysiology of these diseases. The aim of this review was to provide an
      evaluation of what is currently known about the protective role of R381Q variant
      in IL-23R gene in immune-based diseases.

PMID- 27043357
TI  - Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in
      human hepatocellular carcinoma cells.
AB  - Capsaicin, which is the pungent ingredient of red hot chili peppers, has been
      reported to possess anticancer activity, including that against hepatocellular
      carcinoma. However, the precise molecular mechanisms by which capsaicin exerts
      its anticancer effects remain poorly understood. Herein, we have tested the
      involvement of autophagy in the capsaicin mechanism of action in human
      hepatocellular carcinoma. HepG2 cancer cells were treated with different doses of
      capsaicin (50, 100 and 200MUmol/L) for 6, 12, and 24 h. Flow cytometry and
      Caspase-3 activity assay were performed to determine cell apoptosis.
      Immunofluorescence was performed to visualize LC3-positive puncta. Western
      blotting was used to detect the expression of the hallmarks of apoptosis and
      autophagy. Capsaicin can induce apoptosis in HepG2 cells. The expression levels
      of CL-PARP and Bcl-2 were significantly increased. In line with the apoptosis,
      capsaicin can trigger autophagy in HepG2 cells. Capsaicin increased LC3-II and
      beclin-1 expression and GFP-LC3-positive autophagosomes. Pharmacological or
      genetic inhibition of autophagy further sensitized HepG2 cells to capsaicin
      induced apoptosis. Mechanistically, capsaicin upregulated the Stat3 activity
      which contributed to autophagy. Importantly, we found that capsaicin triggered
      reactive oxygen species (ROS) generation in hepatoma cells and that the levels of
      ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC
      abrogated the effects of capsaicin on Stat3-dependent autophagy. In this study,
      we demonstrated that capsaicin increased the phosphorylation of signal transducer
      and activator of transcription 3 (p-STAT3)-dependent autophagy through the
      generation of ROS signaling pathways in human hepatoma. Inhibiting autophagy
      could enhance capsaicin-induced apoptosis in human hepatocellular carcinoma. 

PMID- 27043358
TI  - MAPL: Tissue microstructure estimation using Laplacian-regularized MAP-MRI and
      its application to HCP data.
AB  - The recovery of microstructure-related features of the brain's white matter is a
      current challenge in diffusion MRI. To robustly estimate these important features
      from multi-shell diffusion MRI data, we propose to analytically regularize the
      coefficient estimation of the Mean Apparent Propagator (MAP)-MRI method using the
      norm of the Laplacian of the reconstructed signal. We first compare our approach,
      which we call MAPL, with competing, state-of-the-art functional basis approaches.
      We show that it outperforms the original MAP-MRI implementation and the recently
      proposed modified Spherical Polar Fourier (mSPF) basis with respect to signal
      fitting and reconstruction of the Ensemble Average Propagator (EAP) and
      Orientation Distribution Function (ODF) in noisy, sparsely sampled data of a
      physical phantom with reference gold standard data. Then, to reduce the variance
      of parameter estimation using multi-compartment tissue models, we propose to use
      MAPL's signal fitting and extrapolation as a preprocessing step. We study the
      effect of MAPL on the estimation of axon diameter using a simplified Axcaliber
      model and axonal dispersion using the Neurite Orientation Dispersion and Density
      Imaging (NODDI) model. We show the positive effect of using it as a preprocessing
      step in estimating and reducing the variances of these parameters in the Corpus
      Callosum of six different subjects of the MGH Human Connectome Project. Finally,
      we correlate the estimated axon diameter, dispersion and restricted volume
      fractions with Fractional Anisotropy (FA) and clearly show that changes in FA
      significantly correlate with changes in all estimated parameters. Overall, we
      illustrate the potential of using a well-regularized functional basis together
      with multi-compartment approaches to recover important microstructure tissue
      parameters with much less variability, thus contributing to the challenge of
      better understanding microstructure-related features of the brain's white matter.

PMID- 27043359
TI  - Translational Symptom Science: The Need Is Now.

PMID- 27043360
TI  - Antibacterial activity of a novel fatty acid (14E, 18E, 22E, 26E)-methyl nonacosa
      14, 18, 22, 26 tetraenoate isolated from Amaranthus spinosus.
AB  - CONTEXT: Amaranthus spinosus Linn. (Amaranthaceae), commonly known as ''spiny
      pigweed'', is used in both Indian traditional system and folk medicine for
      treatment of infectious diseases for a long time in several traditional herbal
      medicinal preparations. A novel fatty acid [(14E, 18E, 22E, 26E)-methyl nonacosa
      14, 18, 22, 26 tetraenoate] is the major metabolite present. OBJECTIVE: This
      study examines the antibacterial potential of the fatty acid isolated from the A.
      spinosus against some Gram-positive and Gram-negative bacteria. MATERIALS AND
      METHODS: Three Gram-positive and seven Gram-negative bacterial strains were used
      for antibacterial assay. The minimum inhibitory concentration (MIC) of the fatty
      acid was analysed by dilution method and the effects of the fatty acid on the
      bacterial membrane were studied in detail by flow cytometry analysis. RESULTS AND
      DISCUSSION: All the studied bacterial strains were found to be inhibited at a
      concentration of 100 MUg/mL. Staphylococcus aureus ML-59, Bacillus lycheniformis
      10341, Shigella boydii 8, Vibrio cholera 811, Vibrio cholera 854 and Vibrio
      alginolyteus were susceptible and sensitive to the tested fatty acid with a MIC
      value of 25 MUg/mL. It proved a full spectrum of antibacterial activity
      associated with alterations in the permeability of bacterial membranes.
      CONCLUSION: The fatty acid from the A. spinosus possesses potent antibacterial
      action.

PMID- 27043361
TI  - Detection of Severe Fever with Thrombocytopenia Syndrome Virus from Wild Animals
      and Ixodidae Ticks in the Republic of Korea.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus
      (SFTSV), a novel bunyavirus reported to be endemic to central-northeastern China,
      southern Japan, and the Republic of Korea (ROK). To investigate SFTSV infections,
      we collected serum samples and ticks from wild animals. Using serum samples and
      ticks, SFTSV-specific genes were amplified by one-step RT-PCR and nested PCR and
      sequenced. Indirect immunofluorescence assay (IFA) was performed to analyze virus
      specific antibody levels in wild animals. Serum samples were collected from a
      total of 91 animals: 21 Korean water deer (KWD), 3 Siberian roe deer, 5 gorals, 7
      raccoon dogs, 54 wild boars (WBs), and 1 carrion crow. The SFTSV infection rate
      in wild animals was 3.30% (3 of 91 animals: 1 KWD and 2 WBs). The seropositive
      rate was 6.59% (6 of 91 animals: 5 KWD and 1 WB). A total of 891 ticks (3
      species) were collected from 65 wild animals (9 species). Of the attached tick
      species, Haemaphysalis longicornis (74.86%) was the most abundant, followed by
      Haemaphysalis flava (20.20%) and Ixodes nipponensis (4.94%). The average minimum
      infection rate (MIR) of SFTSV in ticks was 4.98%. The MIRs of H. longicornis, H.
      flava, and I. nipponensis were 4.51%, 2.22%, and 22.73%, respectively. The MIRs
      of larvae, nymphs, and adult ticks were 0.68%, 6.88%, and 5.53%, respectively. In
      addition, the MIRs of fed and unfed ticks were 4.67% and 4.96%, respectively. We
      detected a low SFTSV infection rate in wild animals, no differences in SFTSV
      infection rate with respect to bloodsucking in ticks, and SFTSV infection for all
      developmental stages of ticks. This is the first report describing the detection
      of SFTSV in wild animals in the ROK.

PMID- 27043362
TI  - Regulatory Reply to the ATMOSPHERE Data Monitoring Committee.

PMID- 27043363
TI  - Reaction behavior of SO2 in the sintering process with flue gas recirculation.
AB  - The primary goal of this paper is to reveal the reaction behavior of SO2 in the
      sinter zone, combustion zone, drying-preheating zone, and over-wet zone during
      flue gas recirculation (FGR) technique. The results showed that SO2 retention in
      the sinter zone was associated with free-CaO in the form of CaSO3/CaSO4, and the
      SO2 adsorption reached a maximum under 900oC. SO2 in the flue gas came almost
      from the combustion zone. One reaction behavior was the oxidation of sulfur in
      the sintering mix when the temperature was between 800 and 1000oC; the other
      behavior was the decomposition of sulfite/sulfate when the temperature was over
      1000oC. However, the SO2 adsorption in the sintering bed mainly occurred in the
      drying-preheating zone, adsorbed by CaCO3, Ca(OH)2, and CaO. When the SO2
      adsorption reaction in the drying-preheating zone reached equilibrium, the excess
      SO2 gas continued to migrate to the over-wet zone and was then absorbed by
      Ca(OH)2 and H2O. The emission rising point of SO2 moved forward in combustion
      zone, and the concentration of SO2 emissions significantly increased in the case
      of flue gas recirculation (FGR) technique. IMPLICATIONS: Aiming for the reuse of
      the sensible heat and a reduction in exhaust gas emission, the FGR technique is
      proposed in the iron ore sintering process. When using the FGR technique, SO2
      emission in exhaust gas gets changed. In practice, the application of the FGR
      technique in a sinter plant should be cooperative with the flue gas
      desulfurization (FGD) technique. Thus, it is necessary to study the influence of
      the FGR technique on SO2 emissions because it will directly influence the demand
      and design of the FGD system.

PMID- 27043364
TI  - Developmental effects of fractionated low-dose exposure to gamma radiation on
      behaviour and susceptibility of the cholinergic system in mice.
AB  - PURPOSE: To investigate whether neonatal exposure to fractionated external gamma
      radiation and co-exposure to radiation and nicotine can affect/exacerbate
      developmental neurotoxic effects, including altered behavior/cognitive function
      and the susceptibility of the cholinergic system in adult male mice. MATERIALS
      AND METHODS: Neonatal male Naval Medical Research Institute (NMRI) mice were
      irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 MUg/kg
      b.w.) twice daily on postnatal day (PND) 10, 10-11, 10-12 or 10-13 (nicotine
      only). At 2 months of age the animals were tested for spontaneous behavior in a
      novel home environment, habituation capacity and nicotine-induced behavior.
      RESULTS: Fractionated irradiation and co-exposure to radiation and nicotine on
      three consecutive days disrupted behavior and habituation and altered
      susceptibility of the cholinergic system. All observed effects were significantly
      more pronounced in mice co-exposed to both radiation and nicotine. CONCLUSIONS:
      The fractionated irradiation regime affects behavior/cognitive function in a
      similar manner as has previously been observed for single-dose exposures.
      Neonatal co-exposure to radiation and nicotine, during a critical period of brain
      development in general and cholinergic system development in particular, enhance
      these behavioral defects suggesting that the cholinergic system can be a target
      system for this type of developmental neurotoxic effects.

PMID- 27043365
TI  - What do we know about tailoring treatment with tenofovir?

PMID- 27043366
TI  - ADHD subtypes and neuropsychological performance in an adult sample.
AB  - The study investigated, with an adult sample, the hypothesis that differences
      between subtypes of ADHD on neuropsychological tests contribute to the poor
      separation of ADHD and healthy groups on tests of this kind. Groups of ADHD
      inattentive (n=16) and combined (n=16) subtypes were carefully identified using
      DSM-IV criteria, and their performance on 14 measures of attention, memory, and
      executive function (EF) was compared between subtypes and between the two
      subtypes combined and a group of healthy controls (n=30). Multivariate analyses
      showed statistically significant differences between the two subtypes, and
      between the two subtypes combined and the healthy controls. Importantly for the
      hypothesis, where differences for neuropsychological tests in terms of effect
      sizes between subtypes were largest, the differences in effect sizes between the
      two groups combined and controls were smallest (r=-0.64, 95% CI [-0.15, -0.87]). 

PMID- 27043367
TI  - Developmental delays in phonological recoding among children and adolescents with
      Down syndrome and Williams syndrome.
AB  - This study examined the development of phonological recoding in short-term memory
      (STM) span tasks among two clinical groups with contrasting STM and language
      profiles: those with Down syndrome (DS) and Williams syndrome (WS). Phonological
      recoding was assessed by comparing: (1) performance on phonologically similar and
      dissimilar items (phonological similarity effects, PSE); and (2) items with short
      and long names (word length effects, WLE). Participant groups included children
      and adolescents with DS (n=29), WS (n=25) and typical development (n=51), all
      with average mental ages around 6 years. The group with WS, contrary to
      predictions based on their relatively strong verbal STM and language abilities,
      showed no evidence for phonological recoding. Those in the group with DS, with
      weaker verbal STM and language abilities, showed positive evidence for
      phonological recoding (PSE), but to a lesser degree than the typical group (who
      showed PSE and WLE). These findings provide new information about the memory
      systems of these groups of children and adolescents, and suggest that STM
      processes involving phonological recoding do not fit with the usual expectations
      of the abilities of children and adolescents with WS and DS. 

PMID- 27043368
TI  - Carers' experience of memory screening tests.
AB  - BACKGROUND: Current evidence suggests that patients with dementia find memory
      tests humiliating and embarrassing. However, the knowledge concerning carers'
      experience of witnessing patients with dementia undergo memory screening has not
      been fully explored. AIMS: This study was to explore the experiences of relatives
      of patients with dementia witnessing memory-screening tests. METHOD: Eleven
      relatives of patients with dementia were recruited from three memory clinics
      using a purposive sampling method. A semi-structured questionnaire was used to
      collect data. The data was subjected to thematic analysis. RESULTS: The relatives
      appreciated the memory-screening tests as a diagnostic tool but the majority did
      not understand the questioning in the tests. Witnessing memory-screening tests
      generated anxiety in the relatives and they felt that memory screening tests were
      humiliating for patients. CONCLUSION: A collaborative approach where the
      clinician, the patient and the relative(s) participate in the memory-screening
      tests is advised. Some relatives may benefit from counselling.

PMID- 27043369
TI  - Couples living with and around alcohol abuse: A study of a farmworker community
      in the Cape Winelands, South Africa.
AB  - RATIONALE: Low-income Coloured Western Cape communities in South Africa display
      high rates of problematic drinking, especially binge-drinking over weekends.
      Alcohol abuse in these communities is linked to the prevalence of intimate
      partner violence (IPV), fetal alcohol syndrome and sexual violence against women.
      Few studies, however, have investigated the social contextual factors that
      perpetuate alcohol abuse in these communities. OBJECTIVE AND METHOD: Our study
      contributes to the need for social contextual knowledge need by providing an
      understanding of how committed couples, who lived and worked in one low-income
      historic farm worker community, located in the Cape Winelands of South Africa,
      constructed alcohol use and abuse in their relationship. Using a social
      constructionist grounded theory we analysed the consecutive interviews conducted
      with individual partners. FINDINGS: Three themes shed light on our participants'
      alcohol use discourses. The first theme highlights participants' apparent lack of
      identification with the problem of alcohol abuse, despite the omnipresence of
      alcohol abuse in their accounts. The second theme draws attention to men's and
      women's explicit and implicit support of gendered norms regarding alcohol
      consumption. Linked to the previous, the third theme accentuate women's
      toleration of men's "quiet" weekend binge-drinking. DISCUSSION: We point out the
      limitations of local alcohol policy and intervention efforts to address normative
      drinking discourses and practices in this research community.

PMID- 27043370
TI  - Where the lay and the technical meet: Using an anthropology of interfaces to
      explain persistent reproductive health disparities in West Africa.
AB  - Despite impressive global investment in reproductive health programs in West
      Africa, maternal mortality remains unacceptably high and obstetric care is often
      inadequate. Fertility is among the highest in the world, while contraceptive
      prevalence remains among the lowest. This paper explores the social and technical
      dimensions of this situation. We argue that effective reproductive health
      programs require analyzing the interfaces between technical programs and the
      social logics and behaviors of health professionals and client populations.
      Significant gaps between health programs' goals and the behaviors of patients and
      health care professionals have been observed. While public health projects aim to
      manage reproduction, sexuality, fertility, and professional practices are
      regulated socially. Such projects may target technical practices, but access to
      care is greatly influenced by social norms and ethics. This paper shows how an
      empirical anthropology that investigates the social and technical interfaces of
      reproduction can contribute to improved global health. 

PMID- 27043371
TI  - Can alcohol make you happy? A subjective wellbeing approach.
AB  - There are surprisingly few discussions of the link between wellbeing and alcohol,
      and few empirical studies to underpin them. Policymakers have therefore typically
      considered negative wellbeing impacts while ignoring positive ones, used gross
      overestimates of positive impacts via a naive 'consumer surplus' approach, or
      ignored wellbeing completely. We examine an alternative subjective wellbeing
      method for investigating alcohol and wellbeing, using fixed effects analyses of
      the associations between drinking and wellbeing within two different types of
      data. Study 1 examines wave-to-wave changes in life satisfaction and past-week
      alcohol consumption/alcohol problems (CAGE) from a representative cohort of
      people born in Britain in 1970, utilising responses at ages 30, 34 and 42 (a
      sample size of 29,145 observations from 10,107 individuals). Study 2 examines
      moment-to-moment changes in happiness and drinking from an iPhone-based data set
      in Britain 2010-13, which is innovative and large (2,049,120 observations from
      31,302 individuals) but unrepresentative. In Study 1 we find no significant
      relationship between changing drinking levels and changing life satisfaction (p =
      0.20), but a negative association with developing drinking problems (-0.18 points
      on a 0-10 scale; p = 0.003). In contrast, Study 2 shows a strong and consistent
      moment-to-moment relationship between happiness and drinking events (+3.88 points
      on a 0-100 scale; p < 0.001), although associations beyond the moment in question
      are smaller and more inconsistent. In conclusion, while iPhone users are happier
      at the moment of drinking, there are only small overspills to other moments, and
      among the wider population, changing drinking levels across several years are not
      associated with changing life satisfaction. Furthermore, drinking problems are
      associated with lower life satisfaction. Simple accounts of the wellbeing impacts
      of alcohol policies are therefore likely to be misleading. Policymakers must
      consider the complexity of different policy impacts on different conceptions of
      'wellbeing', over different time periods, and among different types of drinkers. 

PMID- 27043372
TI  - Patients' perceptions and experiences of cardiovascular disease and diabetes
      prevention programmes: A systematic review and framework synthesis using the
      Theoretical Domains Framework.
AB  - BACKGROUND: This review provides a worked example of 'best fit' framework
      synthesis using the Theoretical Domains Framework (TDF) of health psychology
      theories as an a priori framework in the synthesis of qualitative evidence.
      Framework synthesis works best with 'policy urgent' questions. OBJECTIVE: The
      review question selected was: what are patients' experiences of prevention
      programmes for cardiovascular disease (CVD) and diabetes? The significance of
      these conditions is clear: CVD claims more deaths worldwide than any other;
      diabetes is a risk factor for CVD and leading cause of death. METHOD: A
      systematic review and framework synthesis were conducted. This novel method for
      synthesizing qualitative evidence aims to make health psychology theory
      accessible to implementation science and advance the application of qualitative
      research findings in evidence-based healthcare. RESULTS: Findings from 14
      original studies were coded deductively into the TDF and subsequently an
      inductive thematic analysis was conducted. Synthesized findings produced six
      themes relating to: knowledge, beliefs, cues to (in)action, social influences,
      role and identity, and context. A conceptual model was generated illustrating
      combinations of factors that produce cues to (in)action. This model demonstrated
      interrelationships between individual (beliefs and knowledge) and societal
      (social influences, role and identity, context) factors. CONCLUSION: Several
      intervention points were highlighted where factors could be manipulated to
      produce favourable cues to action. However, a lack of transparency of behavioural
      components of published interventions needs to be corrected and further
      evaluations of acceptability in relation to patient experience are required.
      Further work is needed to test the comprehensiveness of the TDF as an a priori
      framework for 'policy urgent' questions using 'best fit' framework synthesis.

PMID- 27043373
TI  - Development of a platform for the discovery and practical synthesis of new
      tetracycline antibiotics.
AB  - Tetracyclines have proven to be safe and effective antibiotics over decades but
      to date all approved members of the class have been discovered and manufactured
      by chemical modification of fermentation products, which greatly limits the
      number of new structures that can be explored as future medicines. This review
      summarizes research leading to the development of a platform synthetic technology
      that enabled the discovery of the clinical candidate eravacycline, as well as
      other promising new tetracycline antibiotics, and provides the basis for a
      practical route for their manufacture. The approach argues for a reassessment of
      other antibiotic classes based on natural products for which practical, fully
      synthetic routes have not yet been developed, suggesting that these may represent
      underdeveloped resources with great potential to offer safer and more effective
      anti-infective agents.

PMID- 27043374
TI  - Research as intervention? Exploring the health and well-being of children and
      youth facing global adversity through participatory visual methods.
AB  - Global health research typically relies on the translation of knowledge (from
      health professionals to the community) and the dissemination of knowledge (from
      research results to the wider public). However, Greenhalgh and Wieringa [2011. Is
      it time to drop the 'knowledge translation' metaphor? A critical literature
      review. Journal of the Royal Society of Medicine, 104(12), 501-509. doi:
      10.1258/jrsm.2011.110285 ] suggest 'that while "translation" is a widely used
      metaphor in medicine, it constrains how we conceptualize and study the link
      between knowledge and practice' (p. 501). Often the knowledge garnered from such
      research projects comes from health professionals rather than reflecting the
      lived experiences of people and communities. Likewise, there has been a gap in
      'translating' and 'disseminating' the results of participatory action research
      projects to policymakers and medical practitioners. This paper will look at how
      using participatory visual methodologies in global health research with children
      and youth facing global adversity incorporates the multiple functions of their
      lived realities so that research becomes a means of intervention. Drawing from a
      literature review of participatory visual methods as media, content and processes
      of global health research, this paper raises practical, theoretical, and ethical
      questions that arise from research as intervention. The paper concludes by
      exploring what lessons emerge when participatory visual methodologies are
      integrated into global health research with children and youth facing global
      adversity.

PMID- 27043375
TI  - Measuring change in clinical profiles between hospital admission and discharge
      and predicting living arrangements at discharge for aged patients presenting
      behavioral and psychological symptoms of dementia.
AB  - BACKGROUND: The clinical courses of psychogeriatric inpatients presenting
      behavioral and psychological symptoms of dementia, between their admission and
      discharge, have been poorly documented. Based upon our previously elaborated
      profiles of psychogeriatric patients, this study aimed to describe these courses
      and to explore whether changing clinical profiles could predict living
      arrangements at discharge. METHODS: Retrospective data were collected on 397
      patients with dementia and hospitalized from 2011 to 2014 in French-speaking
      Switzerland. Patients were classified on admission and at discharge using four
      clinical profiles (BPSD-affective, BPSD-functional, BPSD-somatic, and BPSD
      psychotic). Multinomial logistic regression analyses were used to identify
      predictors of living arrangements at discharge. Age, gender, marital status,
      living arrangements on admission, and clinical profile on admission and
      discharge, were used as potential predictors. RESULTS: Of the patients classified
      as BPSD-functional or BPSD-affective on admission, 70.18% and 73.48%,
      respectively, had the same classification at discharge. However, 45.74% of
      patients classified as BPSD-somatic on admission were discharged with a BPSD
      functional profile, and 46.15% of inpatients classified as BPSD-psychotic on
      admission were discharged as BPSD-affective (chi(2)(9)=128.8299; p<0.000). At
      discharge, 64.99% of all patients were admitted to a nursing home. The
      significant predictors of return to home were: being male (OR=0.96; 95% CI: 0.93
      0.99) and BPSD-affective profile (OR=1.95; 95% CI: 1.08-3.54. Significant
      predictors of transfer to acute care or death were: BPSD-somatic (OR=12.98; 95%
      CI: 1.96-85.91) or BPSD-psychotic profile (OR=13.53; 95% CI: 1.65-111.05).
      DISCUSSION: This study provides new information concerning the clinical course of
      older psychogeriatric inpatients using profiles derived from clinically sensitive
      profiles.

PMID- 27043376
TI  - Adsorption characteristics of nano-TiO2 onto zebrafish embryos and its impacts on
      egg hatching.
AB  - The characteristics of nanoparticles (NPs) uptake may fundamentally alter
      physicochemical effects of engineered NPs on aquatic organisms, thereby yielding
      different ecotoxicology assessment results. The adsorption behavior of nano-TiO2
      (P-25) on zebrafish embryos in Holtfreter's medium (pH 7.2, I ~ 7.2 * 10(-2) M)
      and the presence of sodium alginate (100 mg/L) as dispersant was investigated.
      Zebrafish embryos (total 100) were exposed to nano-TiO2 at different
      concentrations (e.g., 0, 10, 20, 60, 120 mg/L) in batch-mode assay. The
      adsorption capacity of nano-TiO2 on fish eggs was determined by measuring the Ti
      concentration on the egg surface using ICP-OES analysis. Results showed that the
      adsorption capacity increased rapidly in the first hour, and then declined to
      reach equilibrium in 8 h. The adsorption characteristics was visualized as a
      three-step process of rapid initial layer formation, followed by break-up of
      aggregates and finally rearrangement of floc structures; the maximum adsorption
      capacity was the sum of an inner rigid layers of aggregates of 0.81-0.84 MUg
      TiO2/#-egg and an outer softly flocculated layers of 1.01 MUg-TiO2/#-egg. The
      Gibbs free energy was 543.29-551.26 and 100.75 kJ/mol, respectively, for the
      inner-layer and the outer-layer aggregates. Adsorption capacity at 0.5-1.0 MUg
      TiO2/#-egg promoted egg hatching; but hatching was inhibited at higher adsorption
      capacity. Results clearly showed that the configuration of TiO2 aggregates could
      impact the hatching efficiency of zebrafish embryos. 

PMID- 27043377
TI  - Visible-light-driven photodegradation of sulfamethoxazole and methylene blue by
      Cu2O/rGO photocatalysts.
AB  - The cuprous oxide-reduced graphene oxide (Cu2O/rGO-x) composites were prepared
      via a simple wet-chemical method by using CuSO4.5H2O and graphene oxide as
      precursors and ascorbic acid as a reducing agent, respectively. These Cu2O/rGO-x
      were employed as photocatalysts for degrading emerging contaminants and organic
      dye pollutants (i.e., sulfamethoxazole (SMX) and methylene blue (MB)) under
      visible light. A variety of different spectroscopic and analytical techniques,
      such as X-ray diffraction, transmission electron microscopy, X-ray photoelectron
      spectroscopy, Raman scattering spectroscopy and UV-Visible spectroscopy were used
      to characterize the physical properties of photocatalysts. In the photodegrading
      experiments, it can be found that the Cu2O/rGO-80 photocatalyst has the superior
      visible-light response of ca. 50% removal efficiency of SMX within 120 min and
      100% removal efficiency of MB within 40 min. These observations may be attributed
      the well-dispersed and visible-light-responsive Cu2O nanoparticles are supported
      on the surface of rGO sheets that can enhance absorption of visible light during
      photocatalysis. 

PMID- 27043378
TI  - Cytotoxic and genotoxic potential of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA
      complex in human hepatoma (HepG2) cells.
AB  - Chromium (Cr) and ethylenediaminetetraacetate (EDTA) are common environmental
      pollutants and can be present in high concentrations in surface waters at the
      same time. Therefore, chelation of Cr with EDTA can occur and thereby stable
      Cr(III)-EDTA complex is formed. Since there are no literature data on Cr(III)
      EDTA toxicity, the aim of our work was to evaluate and compare Cr(III)-EDTA
      cytotoxic and genotoxic activity with those of Cr(VI) and Cr(III)-nitrate in
      human hepatoma (HepG2) cell line. First the effect of Cr(VI), Cr(III)-nitrate and
      Cr(III)-EDTA on cell viability was studied in the concentration range from 0.04
      MUg mL(-1) to 25 MUg mL(-1) after 24 h exposure. Further the influence of non
      cytotoxic concentrations of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA on DNA
      damage and genomic stability was determined with the comet assay and cytokinesis
      block micronucleus cytome assay, respectively. Cell viability was decreased only
      by Cr(VI) at concentrations above 1.0 MUg mL(-1). Cr(VI) at >=0.2 MUg mL(-1) and
      Cr(III) at >=1.0 MUg mL(-1) induced DNA damage, while after Cr(III)-EDTA exposure
      no formation DNA strand breaks was determined. Statistically significant
      formation of micronuclei was induced only by Cr(VI) at >=0.2 MUg mL(-1), while no
      influence on the frequency of nuclear buds nor nucleoplasmic bridges was observed
      at any exposure. This study provides the first evidence that Cr(III)-EDTA did not
      induce DNA damage and had no influence on the genomic stability of HepG2 cells. 

PMID- 27043379
TI  - Adsorption and regenerative oxidation of trichlorophenol with synthetic zeolite:
      Ozone dosage and its influence on adsorption performance.
AB  - Regeneration of loaded adsorbents is a key step for the sustainability of an
      adsorption process. In this study, ozone was applied to regenerate a synthetic
      zeolite for the adsorption of trichlorophenol (TCP) as an organic model
      pollutant. Three initial concentrations of TCP in water phase were used in
      adsorption tests. After the equilibrium, zeolite loaded different amounts of TCP
      was dried and then regenerated with ozone gas. It was found that the adsorption
      capacity of zeolite was increased through three regeneration cycles. However, the
      adsorption kinetics was compromised after the regeneration with slightly declined
      2nd order reaction constants. The ozone demand for the regeneration was highly
      dependent on the TCP mass loaded onto the zeolite. It was estimated that the mass
      ratio of ozone to TCP was 1.2 +/- 0.3 g O3/g TCP. 

PMID- 27043380
TI  - The polychlorinated dibenzofuran fingerprint of iron ore sinter plant: Its
      persistence with suppressant and alternative fuel addition.
AB  - An earlier demonstration that the relative concentrations of isomers of
      polychlorinated dibenzofuran do not vary as the flamefront of an iron ore sinter
      plant progresses through the bed, and profiles are similar for two sinter strands
      has been widened to include studies of the similarity or otherwise between full
      scale strand and sinter pot profiles, effect of addition of suppressants and of
      coke fuel substitution with other combustible materials. For dioxin suppressant
      addition, a study of the whole of the tetra- penta- and hexaCDF isomer range as
      separated by the DB5MS chromatography column, indicates no significant change in
      profile: examination of the ratios of the targeted penta- and hexaCDF isomers
      suggests the profile is similarly unaffected by coke fuel replacement. Addition
      of KCl at varied levels has also been shown to have no effect on the
      'fingerprint' and there is no indication of any effect by the composition of the
      sinter mix. The recently published full elution sequence for the DB5MS column is
      applied to the results obtained using this column. It is confirmed that isomers
      with 1,9-substitution of chlorine atoms are invariably formed in low
      concentrations. This is consistent with strong interaction between the 1 and 9
      substituted chlorine atoms predicted by DFT thermodynamic calculations. Non-1,9
      substituted PCDF equilibrium isomer distributions based on DFT-derived
      thermodynamic data differ considerably from stack gas distributions obtained
      using SP2331 column separation. A brief preliminary study indicates the same
      conclusions (apart from the 1,9-interaction effect) hold for the much smaller
      content of PCDD. 

PMID- 27043381
TI  - Toxicological effects of polychlorinated biphenyls (PCBs) on freshwater turtles
      in the United States.
AB  - Prediction of vertebrate health effects originating from persistent organic
      pollutants (POPs) such as polychlorinated biphenyls (PCBs) has remained a
      challenge for decades thus making the identification of bioindicators difficult.
      POPs are predominantly present in soil and sediment, where they adhere to
      particles due to their hydrophobic characteristics. Animals inhabiting soil and
      sediment can be exposed to PCBs via dermal exposure while others may obtain PCBs
      through contaminated trophic interaction. Freshwater turtles can serve as
      bioindicators due to their strong site fidelity, longevity and varied diet.
      Previous research observed the health effects of PCBs on turtles such as
      decreased bone mass, changed sexual development and decreased immune responses
      through studying both contaminated sites along with laboratory experimentation.
      Higher deformity rates in juveniles, increased mortality and slower growth have
      also been observed. Toxicological effects of PCBs vary between species of
      freshwater turtles and depend on the concertation and configuration of PCB
      congeners. Evaluation of ecotoxicological effects of PCBs in non-endangered
      turtles could provide important knowledge about the health effects of endangered
      turtle species thus inform the design of remediation strategies. In this review,
      the PCB presence in freshwater turtle habitats and the ecotoxicological effects
      were investigated with the aim of utilizing the health status to identify areas
      of focus for freshwater turtle conservation. 

PMID- 27043382
TI  - Antimicrobial susceptibility of Clostridium difficile isolated from food animals
      on farms.
AB  - Clostridium difficile is commonly associated with a spectrum of disease in humans
      referred to as C. difficile-associated disease (CDAD) and use of antimicrobials
      is considered a risk factor for development of disease in humans. C. difficile
      can also inhabit healthy food animals and transmission to humans is possible. As
      a result of the complexity and cost of testing, C. difficile is rarely tested for
      antimicrobial susceptibility. A total of 376 C. difficile strains (94 each from
      swine and dairy feces, and 188 from beef cattle feces) were isolated from healthy
      food animals on farms during studies conducted by the National Animal Health
      Monitoring System. Using the Etest (AB Biodisk, Solna, Sweden), samples were
      tested for susceptibility to nine antimicrobials implicated as risk factors for
      CDAD (linezolid, amoxicillin-clavulanic acid, ampicillin, clindamycin,
      erythromycin, levofloxacin, metronidazole, rifampicin, and vancomycin).
      Vancomycin was active against all isolates of C. difficile (MIC90=3.0MUg/ml)
      while almost all isolates (n=369; 98.1%) were resistant to levofloxacin. With the
      exception of vancomycin, resistance varied by animal species as follows:
      linezolid (8.5% resistance among swine versus 2.1 and 1.1% resistance among dairy
      and beef, respectively), clindamycin (56.4% resistance among swine versus 80% and
      90.9% resistance among dairy and beef, respectively), and rifampicin (2.1% and 0%
      resistance among swine and dairy cattle isolates, respectively versus 14.3%
      resistance among beef isolates). Regardless of species, multiple drug resistance
      was observed most often to combinations of clindamycin and levofloxacin (n=195;
      51.9%) and ampicillin, clindamycin and levofloxacin (n=41; 10.9%). The reason for
      the variability of resistance between animal species is unknown and requires
      further research. 

PMID- 27043383
TI  - Growth and aggressiveness factors affecting Monilinia spp. survival peaches.
AB  - Brown rot of stone fruit is caused by three species of Monilinia, Monilinia laxa,
      M. fructigena, and M. fructicola. Eleven components of 20 different isolates of
      each of the three Monilinia species were analyzed to determine distinct
      aggressiveness and growth characteristics among the three fungi. M. fructicola
      showed the greatest lesion diameter, and the lowest incubation and latency period
      on fruit postharvest, however isolates of M. fructigena exhibited less
      aggressiveness components. Five growth characteristics of M. fructicola could be
      used to distinguish M. fructicola from the other two species. The dendrogram
      generated from only the presence of sclerotia and lesion length on infected fruit
      separated the 60 isolates into two clusters (r=0.93). One cluster was composed of
      the M. laxa and M. fructigena isolates and the other cluster comprised the M.
      fructicola isolates. However, the dendrogram generated based on the presence of
      stromata and sclerotia in the same colony of the three species when they were
      grown on potato dextrose agar, and the lesion diameter on fruit infected with
      each species separated the 60 isolates into three clusters (r=0.81). Each cluster
      comprised the isolates of each of three Monilinia spp. We discussed the effect of
      M. fructicola growth and aggressiveness differences on the displacement of M.
      laxa and M. fructigena by M. fructicola recorded in Spanish peach orchards and
      their effect on brown rot at postharvest. 

PMID- 27043384
TI  - A revised method of examining fish for infection with zoonotic nematode larvae.
AB  - The infection of fish with zoonotic nematodes, particularly anisakid nematodes is
      of great interest to many researchers who study food safety, human or animal
      health or who use them as biological tags for stock assessment studies. Accurate
      examination of fish for infection with anisakid larvae is crucial in making
      accurate estimates of their occurrence, abundance and prevalence in their fish
      hosts. Here we describe a new method of examining fish for infection with these
      parasites. In 2015, a total of 261 fish were purchased from a fish market in New
      South Wales, Australia. All fish were first examined by routine visual
      examination for infection with zoonotic nematode larvae and all data were
      recorded. Subsequently all internal organs were placed in a container and filled
      with water and incubated in the room temperature overnight. The prevalence, mean
      intensity and mean abundance of anisakids were significantly higher (p<0.05) when
      the revised method of examination, i.e., combining visual examination and
      overnight incubation in room temperature, was employed (63.98, 8.23 and 5.27,
      respectively) compared to routine visual examination with or without the aid of a
      microscope (8.81, 3.78 and 0.33, respectively). The proposed method is effective
      and has several advantages, such as: not using UV or HCl for fish examination,
      allowing the examination of a larger number of fish in shorter time; larval
      specimens collected being suitable for both morphological and DNA sequencing; and
      being simple and inexpensive. The disadvantages would be the odour of the
      specimens after overnight incubation as well as not being suitable for use with
      frozen fish. We suggest that results, conclusions or recommendations made in
      studies that claim no anisakid/ascaridoid larvae were found in a fish should be
      approached carefully if it is only based on visual examination of the fish. 

PMID- 27043385
TI  - Synergistic bactericidal action of phytic acid and sodium chloride against
      Escherichia coli O157:H7 cells protected by a biofilm.
AB  - The food industry must prevent the build-up of strong Escherichia coli O157:H7
      biofilms in food processing environments. The present study examined the
      bactericidal action of phytic acid (PA), a natural extract from rice bran and the
      hulls/peels of legumes, against E. coli O157:H7 biofilms. The synergistic
      bactericidal effects of PA plus sodium chloride (NaCl) were also examined. E.
      coli O157:H7 biofilms were allowed for form on stainless steel coupons by culture
      in both rich (tryptic soy broth, TSB) and minimal (M9) medium at 22 degrees C for
      6days. Bacterial cells within biofilms grown in M9 medium were significantly more
      resistant to PA than those grown in TSB (p<0.05); thus M9 medium was selected for
      further experiments. The anti-biofilm effect of PA was significantly increased by
      addition of NaCl (2-4%) (p<0.05); indeed, the combination of 0.4% PA plus 3-4%
      NaCl completely inactivated E. coli O157:H7 biofilms without recovery
      (a>6.5logCFU/cm(2) reduction). Neither PA nor NaCl alone were this effective (PA,
      1.6-2.7logCFU/cm(2) reduction; NaCl, <0.5logCFU/cm(2) reduction). Confocal laser
      scanning microscopy images of propidium iodide-treated cells showed that PA
      (0.4%) plus NaCl (2-4%) had marked membrane permeabilizing effects. These results
      suggest that a sanitizer that combines these two naturally occurring
      antimicrobial agents may be useful to food safety managers who encounter thick
      biofilm formation in food processing environments. 

PMID- 27043386
TI  - Cognitive-behavioral changes in amyotrophic lateral sclerosis: Screening
      prevalence and impact on patients and caregivers.
AB  - Our objective was to evaluate the association between cognitive-behavioral
      deficits and patient quality of life (QoL), caregiver burden, and disease stage
      in a population of patients with amyotrophic lateral sclerosis (ALS). We
      administered the ALS Cognitive-Behavioral ScreenTM to 86 patients with ALS.
      Multiple regression was used to evaluate the association between cognitive or
      behavioral deficits and disease stage, patient QoL, and caregiver burden while
      controlling for clinically important variables. Of 86 participants enrolled, 53
      (62%) had some degree of cognitive impairment, 32 (37%) were behaviorally
      impaired and four met both cognitive and behavioral screening criteria for
      frontotemporal dementia (FTD). The severity of cognitive-behavioral deficits was
      not associated with patient QoL. More pronounced cognitive deficits (beta = -1.4,
      p = 0.04) and behavioral symptoms (-0.69, p < 0.001) predicted higher caregiver
      burden. Self-reported QoL was lower in patients with more depressive symptoms
      (beta = -0.32, p < 0.001) and more advanced disease (beta =0.10, p = 0.01). In
      conclusion, general QoL for patients with ALS is not associated with cognitive or
      behavioral deficits. More severe cognitive deficits and caregiver-reported
      behavioral symptoms predict higher caregiver burden. Routine cognitive-behavioral
      screening can identify patients who require full neuropsychological examination,
      inform patient counseling, and identify caregivers in need of early, targeted
      interventions.

PMID- 27043387
TI  - Strain Engineering for Transition Metal Dichalcogenides Based Field Effect
      Transistors.
AB  - Using electrical characteristics from three-terminal field-effect transistors
      (FETs), we demonstrate substantial strain induced band gap tunability in
      transition metal dichalcogenides (TMDs) in line with theoretical predictions and
      optical experiments. Devices were fabricated on flexible substrates, and a
      cantilever sample holder was used to apply uniaxial tensile strain to the various
      multilayer TMD FETs. Analyzing in particular transfer characteristics, we argue
      that the modified device characteristics under strain are clear evidence of a
      band gap reduction of 100 meV in WSe2 under 1.35% uniaxial tensile strain at room
      temperature. Furthermore, the obtained device characteristics imply that the band
      gap does not shrink uniformly under strain relative to a reference potential
      defined by the source/drain contacts. Instead, the band gap change is only
      related to a change of the conduction band edge of WSe2, resulting in a decrease
      in the Schottky barrier (SB) for electrons without any change for hole injection
      into the valence band. Simulations of SB device characteristics are employed to
      explain this point and to quantify our findings. Last, our experimental results
      are compared with DFT calculations under strain showing excellent agreement
      between theoretical predictions and the experimental data presented here.

PMID- 27043388
TI  - Genetics of Congenital Cataract.
AB  - Congenital cataract is a type of cataract that presents at birth or during early
      childhood, and it is one of the most easily treatable causes of visual impairment
      and blindness during infancy, with an estimated prevalence of 1-6 cases per
      10,000 live births. Approximately 50% of all congenital cataract cases may have a
      genetic cause, and such cases are quite heterogeneous. Although congenital
      nuclear cataract can be caused by multiple factors, genetic mutation remains the
      most common cause. All three types of Mendelian inheritance have been reported
      for cataract; however, autosomal dominant transmission seems to be the most
      frequent. The transparency and high refractive index of the lens are achieved by
      the precise architecture of fiber cells and homeostasis of the lens proteins in
      terms of their concentrations, stabilities, and supramolecular organization.
      Research on hereditary congenital cataract has led to the identification of
      several classes of candidate genes that encode proteins such crystallins, lens
      specific connexins, aquaporin, cytoskeletal structural proteins, and
      developmental regulators. In this review, we highlight the identified genetic
      mutations that account for congenital nuclear cataract. 

PMID- 27043389
TI  - State of the Art in Pediatric Cataract Surgery.
AB  - Pediatric cataract surgery has evolved dramatically in the past 10 years. Our
      understanding of the child's eye both in terms of tissue mechanics,
      neurobiological plasticity and physiological growth has allowed better and better
      surgical outcomes. The fact remains that the younger the child - infants
      especially - the more difficult the surgery. It is also true to say that not only
      is a child's eye not a small adult eye, but also that the child him- or herself
      is not a small adult. The importance of this statement is evident when we discuss
      the effects of anesthesia and fluid input in infants during infant cataract
      surgery. This chapter discusses the factors that should help give a child the
      best possible outcome after cataract surgery including timing of surgery, type of
      operation, biometry, the size and type of intraocular lens material ,
      postoperative refraction, operative considerations, wound size and type, capsule
      management, anterior vitrectomy technique, wound closure and viscoelastic removal
      and perioperative medications. 

PMID- 27043390
TI  - Changes in Ocular Growth after Pediatric Cataract Surgery.
AB  - The human eye undergoes extensive changes during early childhood, including axial
      elongation, corneal flattening and reduced lens power. Animal studies have shown
      that removing the crystalline lens during infancy retards axial elongation. Axial
      elongation has been studied in children after cataract extraction both directly
      and indirectly. Children with a unilateral congenital cataract generally have a
      shorter axial length in their cataractous eye than in their fellow eye. This
      difference usually persists after cataract surgery. While some studies have
      reported a modest reduction in axial elongation after cataract extraction, the
      magnitude of this effect is much less than what has been reported in animal
      models. Choosing an intraocular lens (IOL) power for implantation into a child's
      eye is complicated by continued ocular growth, the inaccuracy of IOL power
      calculation formulas for small eyes, and the difficulty of accurately measuring
      the biometrics of a child's eye. In addition, given the fixed position of an IOL
      in the eye, increasing elongation of the posterior segment of the eye relative to
      the anterior segment magnifies the myopic shift that occurs with ocular growth.
      The targeted refractive error in young children undergoing IOL implantation
      should be an undercorrection in anticipation of a future myopic shift. 

PMID- 27043391
TI  - Incidence of and Risk Factors for Postoperative Glaucoma and Its Treatment in
      Paediatric Cataract Surgery.
AB  - Postoperative glaucoma is perhaps the most feared complication after paediatric
      cataract surgery, as it is difficult to control. Paediatric glaucoma is also
      challenging to diagnose, and different definitions of glaucoma have led to a
      rather big range of reported incidences of this disease. It can occur soon after
      surgery, in which case it is usually closed-angle glaucoma, or it can have a late
      onset, even more than a decade after surgery, and its aetiopathogenesis remains
      unclear to this day. There is significant controversy as to what the risk factors
      are for developing it, especially regarding intraocular lens implantation. The
      vast majority of studies show that an earlier age at surgery confers a higher
      risk. Medical and surgical treatment of aphakic/pseudophakic glaucoma can be
      successful; however, management often requires repeated procedures with or
      without multiple medications, and the prognosis is guarded. The visual outcome
      depends on sufficient intraocular pressure control and management of concurrent
      amblyopia. 

PMID- 27043392
TI  - Visual Rehabilitation in Pediatric Aphakia.
AB  - The management of childhood cataract begins at the initial contact with the
      family and typically extends far into the child's future. Decisions affecting
      long-term care and visual outcomes are often made in these initial preoperative
      encounters. Treatment will vary depending on whether the cataract is unilateral
      or bilateral and whether it is infantile onset or later. Thorough discussion of
      the treatment options is needed, especially with description of the life-long
      management issues for the child. Visual outcomes will vary, with the best visual
      acuity results being observed in older children with bilateral cataracts. Visual
      rehabilitation of children with unilateral cataract requires use of a contact
      lens or an intraocular lens (IOL) for the best result with a chance for
      binocularity. Only about 50% of eyes with unilateral infantile cataract will
      develop vision of better than 20/200. For bilateral cataracts, both contacts and
      IOLs can be used, as well as aphakic glasses. Excellent visual outcomes are
      typical unless glaucoma develops, which occurs in up to 30% of cases. Cataract
      surgery after 1 year of age is associated with substantially better visual
      outcomes. The use of an IOL is most commonly accepted and performed for cataract
      in one or both eyes after 1 year of age. Prior to 1 year of age, significantly
      more secondary surgical procedures are required to manage opacification of the
      optical axis with the use of an IOL compared with the use of surgery and contact
      lens correction. Amblyopia therapy for unilateral cataract needs be continuous
      from the time of surgery until at least 8 years of age. It is often difficult to
      perform this therapy over such a long time period, with compliance with less than
      30% of prescribed time during infancy at 5 years after surgery. 

PMID- 27043393
TI  - Complications of Pediatric Cataract Surgery.
AB  - Postoperative complications associated with cataract surgery in children vary
      significantly from those typically seen in adults. Pediatric patients are at an
      increased risk of problems after intraocular surgery due to increased ocular
      elasticity, heightened inflammatory reactions, and an elevated risk of
      postoperative trauma. Any complication is particularly important to detect early
      in children due to the potential for aberrant development, which may result in
      decreased visual acuity. Further, complications arise throughout the immediate
      and extended postoperative periods that may be challenging to detect given the
      difficulty of the clinical examination of some young patients. Herein, we address
      common complications observed during the immediate postoperative period and
      during the months and years following cataract surgery in pediatric patients. 

PMID- 27043394
TI  - Complex Cases in Pediatric Cataract.
AB  - This chapter describes the techniques and pitfalls that the reader may come
      across when dealing with complex pediatric cataract cases. Each eye in these
      circumstances is unique, and the examples and general advice shared are intended
      to help the reader develop a plan for surgery and a road map to avoid potential
      problems. As in all types of surgery, careful planning is essential. The old
      saying 'Fail to prepare, then you prepare to fail' is no more true than when
      dealing with children who have complex cataract. In this chapter, the following
      circumstances where pediatric cataract may be seen are discussed: retinoblastoma,
      retinopathy of prematurity, lenticonus, congenital rubella syndrome, trauma,
      microcornea, pediatric uveitis, Hallermann-Streiff syndrome, Stickler syndrome,
      Lowe syndrome, subluxated lens, and after previous intraocular surgery (glaucoma,
      keratoplasty). 

PMID- 27043395
TI  - The DCCN Editorial Team: Celebrating Our Team and Welcoming New Talents.

PMID- 27043397
TI  - Implementing a Distraction-Free Practice With the Red Zone Medication Safety
      Initiative.
AB  - BACKGROUND: The incidence of medication errors remains a continued concern across
      the spectrum of health care. Approaches to averting medication errors and
      implementing a culture of safety are key areas of focus for most institutions. We
      describe our experience of implementing a distraction-free medication safety
      practice across a large free-standing children's hospital. METHODS: A nurse-led
      interprofessional group was convened to develop a program-wide quality
      improvement process for the practice of medication safety. A key driver diagram
      was developed to guide the Red Zone Medication Safety initiative. Change
      acceleration process was used to evaluate the implementation and impact of the
      initiative. RESULTS: Since implementation in 2010, there has been a significant
      reduction in medication events of 79.2% (P = .00184) and 65.3% (P = .035) (in the
      cardiac intensive care unit and acute care cardiac unit, respectively), including
      months with unprecedented zero reportable medication events. There also has been
      a sustained decrease in the number of events reaching the patient (33.3% in the
      cardiac intensive care unit and 57.1% in the acute care cardiac unit).
      CONCLUSIONS: The implementation of a distraction-free practice was found to be
      feasible and effective, demonstrating a sustained decrease in the overall number
      of medication events, event rate, and number of events reaching patients. This
      interprofessional approach was successful in a large inpatient cardiovascular
      program and then effectively transferred across all hospital inpatient units.
      Additional sites of implementation include other high-risk patient care areas
      such as procedure/operative units.

PMID- 27043398
TI  - Symptoms Experienced by Jordanian Men and Women After Coronary Artery Bypass
      Graft Surgery.
AB  - BACKGROUND: Patients who undergo coronary artery bypass graft (CABG) surgery
      experience a wide spectrum of physical and psychological symptoms after surgery.
      Studies have shown that symptoms usually decline over time; however, some can
      persist up to months after discharge. OBJECTIVES: This study aims to assess
      symptoms experienced by patients after CABG surgery and any associations with
      demographic variables. METHODS: A descriptive, cross-sectional design was used. A
      convenience sample of 100 Jordanian post-CABG surgery patients was selected from
      5 hospitals in Jordan. Patients were surveyed using the Cardiac Symptom Survey.
      To examine the associations between the symptoms experienced and selected
      demographic variables, chi(2) analyses were used. RESULTS: Chest incisional pain
      (65%) was the most frequently perceived symptom by the participants. Leg swelling
      (60%) was also reported by a nearly equivalent number of respondents. Symptoms
      like fluttering (15%), angina (8%), and depression (3%) were reported by a
      handful of participants. Three symptoms (poor appetite, sleeping problem, and
      fatigue) had significant associations with demographic variables. DISCUSSION: The
      identification of frequently perceived symptoms among post-CABG patients enables
      health care providers to focus their assessments in identifying and alleviating
      them. The demographic associations identified facilitate nurses to forecast
      certain specific symptoms in targeted populations, like women are more prone to
      experience poor appetite and sleeping difficulties and strengthen these groups
      with strategies to prevent themselves from these distressing symptoms.

PMID- 27043399
TI  - Intrahospital Transport of the Critically Ill Adult: A Standardized Evaluation
      Plan.
AB  - BACKGROUND: Intrahospital transport of the critically ill adult carries inherent
      risks that can be manifested as unexpected events. OBJECTIVE: The aim of this
      study is to evaluate the implementation of a standardized evaluation plan for
      intrahospital transports to/from adult intensive care units. METHODS: Nurses at a
      level I trauma/academic center captured clinical data throughout transport.
      Outcome measures included compliance with the organization's transport policy and
      unexpected events. RESULTS: There were 502 transports audited. Most nurses were
      compliant with the policy, except for the stabilization process (n = 174, 34.7%).
      Forty-one transports (8.2%) had an unexpected event, and 11 of these transports
      (26.8%) were aborted. Most of the events were hemodynamic (12), sedation (11),
      respiratory (10), and gastrointestinal (5). Fewer events occurred with the
      transport team (P = .036) and among nurses with a bachelor of science in nursing
      or higher degree (P = .002). Events were higher among transporting nurses with
      only 0 to 2 years of intensive care unit experience (P = .002), "stabilized"
      transports (P = .022), and patients with higher Acute Physiology and Chronic
      Health Evaluation scores (P = .009). CONCLUSIONS: Health care organizations
      should have a policy that includes both transport and evaluation plans for
      intrahospital transport. Guidelines should be revised with specific criteria for
      the stabilization process and unexpected events. Revision should also have a
      standardized evaluation plan that includes an audit tool to measure incidence of
      unexpected events and a rapid change quality improvement method.

PMID- 27043400
TI  - Strategies for Pursuing a Master's Degree.
AB  - Health care has become very complex and is in a constant state of change. As a
      result of the evolving change and increasing complexity, a more educated nursing
      workforce is needed (Dracup K. Master's nursing programs. American Association of
      Colleges of Nursing. 2015; Institute of Medicine. The Future of Nursing: Leading
      Change, Advancing Health. 2010). It is now becoming necessary for registered
      nurses to earn an advanced degree to work at the highest level of their practice
      authority (Dracup K. Master's nursing programs. American Association of Colleges
      of Nursing. 2015; Institute of Medicine. The Future of Nursing: Leading Change,
      Advancing Health. 2010.). Preparing to reenter college may be an overwhelming
      prospect for some registered nurses seeking an advanced degree. However, there
      are some simple strategies that may help sort out the many degree options,
      financial obligations, decisions about brick and mortar versus online learning,
      commitment to degree completion, and changing career paths. This article will
      provide the registered nurse valuable information that will assist in the
      exciting process of returning to college. 

PMID- 27043401
TI  - Nursing Interactions With Intensive Care Unit Patients Affected by Sleep
      Deprivation: An Observational Study.
AB  - BACKGROUND: Patients in intensive care units (ICUs) often experience sleep
      deprivation due to different factors. Its consequences are damaging both
      physiologically and psychologically. This study focuses particularly on nursing
      interactions as the main factor involved in sleep deprivation issues. OBJECTIVES:
      The aims of this study were to examine the frequency, pattern, and types of
      nocturnal care interactions with patients in the respiratory and cardiology ICUs;
      analyze the relationship between these interactions and patients' variables (age,
      sex, recovery diagnosis, and acuity of care); and analyze the differences in
      patterns of nocturnal care interactions among the units. METHODS: This is an
      observational retrospective study that analyzes the frequency, pattern, and types
      of nocturnal care interactions with patients between 7 PM and 6 AM recording data
      in the activity data sheets. RESULTS: Data consisted of 93 data assessment
      sheets. The mean number of care interactions per night was 18.65 (SD, 3.71). In
      both ICUs, interactions were most frequent at 7 PM, 10 PM, and 6 AM. Only 8
      uninterrupted sleep periods occurred. Frequency of interactions correlated
      significantly with patients' acuity scores and the number of nurse interventions
      in both ICUs. CONCLUSIONS: Patients in ICUs have fragmented sleep patterns. This
      study underlines the need to develop new management approaches to promote and
      maintain sleep.

PMID- 27043402
TI  - Family Experiences During the Dying Process After Withdrawal of Life-Sustaining
      Therapy.
AB  - BACKGROUND: Life-sustaining therapy is commonly withdrawn in intensive care
      units, yet little is known about the perceptions of families when a critically
      ill patient dies after life-sustaining therapy is withdrawn. AIM: The purpose of
      this investigation was to understand the experience of families when a family
      member had an unexpected life-threatening illness or injury and who died after
      life-sustaining therapy was withdrawn. METHODS: This investigation used a
      hermeneutic phenomenological approach. Interviews were conducted with family
      members after the patient's death. All interviews were transcribed with units of
      meaning and clusters, and then categories inductively determined. Methodological
      rigor was established. SETTING/PARTICIPANTS: A purposive sample of family members
      was recruited into the study from 3 intensive care units. Twenty-two family
      members participated in the study. RESULTS: Six categories evolved from the
      analysis: preparing for the dying process, the dying environment, perceptions of
      patient comfort, the death vigil, essential aspects of care, and together as a
      family. Families described the death vigil as extremely difficult. Family members
      described several aspects of care as very meaningful to them during the dying
      process. Families described how important it was for the family to be together as
      a family during the dying process.

PMID- 27043405
TI  - Letter to the Editor.

PMID- 27043406
TI  - To Our Peer Reviewers: With Gratitude and Respect.

PMID- 27043407
TI  - Rituximab for Recurrence of Primary Focal Segmental Glomerulosclerosis After
      Kidney Transplantation: Clinical Outcomes.
AB  - BACKGROUND: Rituximab has shown encouraging results for the treatment of kidney
      transplantation recipients with focal segmental glomerulosclerosis (FSGS)
      recurrence. However, the correct, opportune, and safe use of rituximab for this
      indication remains to be determined. METHODS: This multicenter retrospective
      study reports on 19 new cases aged 35 (15-66) years who developed FSGS recurrence
      at 12 (1.5-27) days posttransplantation. Initial treatment consisted of plasma
      exchanges (PE), high doses of calcineurin inhibitors, and steroids. Rituximab was
      introduced either immediately (N = 6) or after failure of the initial treatment
      (N = 10) or failed attempted weaning from PE (N = 3). RESULTS: Overall, we
      observed 9 of 19 complete remissions and 3 of 19 partial remissions. Estimated
      glomerular filtration rates (Modification of Diet in Renal Disease 4) were
      significantly higher in the responding patients than in nonresponding patients at
      month (M)12, M36, and M60. Overall, kidney survival at 5 years was 77.4% (95%
      range, 41.9-92.7). The 5-year graft survival rates in the responding patients and
      the nonresponding patients were 100% and 36.5%, respectively (P = 0.01). A
      further course of rituximab was required for 4 patients as a result of FSGS
      relapse, with good results. During the first year after renal transplantation, 14
      patients developed severe infections (16 bacterial, 4 viral, 1 parasitic).
      CONCLUSIONS: In kidney transplantation recipients with recurrent FSGS, rituximab
      therapy may be a recommended treatment for cases that have failed either the
      initial treatment or weaning from PE.

PMID- 27043408
TI  - The intracellular pathway for the presentation of vitamin B-related antigens by
      the antigen-presenting molecule MR1.
AB  - The antigen-presenting molecule MR1 presents vitamin B-related antigens (VitB
      antigens) to mucosal-associated invariant T (MAIT) cells through an
      uncharacterized pathway. We show that MR1, unlike other antigen-presenting
      molecules, does not constitutively present self-ligands. In the steady state it
      accumulates in a ligand-receptive conformation within the endoplasmic reticulum.
      VitB antigens reach this location and form a Schiff base with MR1, triggering a
      'molecular switch' that allows MR1-VitB antigen complexes to traffic to the
      plasma membrane. These complexes are endocytosed with kinetics independent of the
      affinity of the MR1-ligand interaction and are degraded intracellularly, although
      some MR1 molecules acquire new ligands during passage through endosomes and
      recycle back to the surface. MR1 antigen presentation is characterized by a rapid
      'off-on-off' mechanism that is strictly dependent on antigen availability. 

PMID- 27043409
TI  - Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling
      type 2 inflammation.
AB  - Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair
      after activation by cell-extrinsic factors such as host-derived cytokines.
      However, the cell-intrinsic metabolic pathways that control ILC2 function are
      undefined. Here we demonstrate that expression of the enzyme arginase-1 (Arg1)
      during acute or chronic lung inflammation is a conserved trait of mouse and human
      ILC2s. Deletion of mouse ILC-intrinsic Arg1 abrogated type 2 lung inflammation by
      restraining ILC2 proliferation and dampening cytokine production.
      Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple
      components of ILC2 metabolic programming by altering arginine catabolism,
      impairing polyamine biosynthesis and reducing aerobic glycolysis. These data
      identify Arg1 as a key regulator of ILC2 bioenergetics that controls
      proliferative capacity and proinflammatory functions promoting type 2
      inflammation.

PMID- 27043410
TI  - Distinct myeloid progenitor-differentiation pathways identified through single
      cell RNA sequencing.
AB  - According to current models of hematopoiesis, lymphoid-primed multi-potent
      progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid
      progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early
      branch point for separate lineage-commitment pathways from hematopoietic stem
      cells, with the notable exception that both pathways are proposed to generate all
      myeloid innate immune cell types through the same myeloid-restricted pre
      granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(
      )FcgammaRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of
      pre-GMs, we identified distinct myeloid differentiation pathways: a pathway
      expressing the gene encoding the transcription factor GATA-1 generated mast
      cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking
      expression of that gene generated monocytes, neutrophils and lymphocytes. These
      results identify an early hematopoietic-lineage bifurcation that separates the
      myeloid lineages before their segregation from other hematopoietic-lineage
      potential.

PMID- 27043411
TI  - Late stages of T cell maturation in the thymus involve NF-kappaB and tonic type I
      interferon signaling.
AB  - Positive selection occurs in the thymic cortex, but critical maturation events
      occur later in the medulla. Here we defined the precise stage at which T cells
      acquired competence to proliferate and emigrate. Transcriptome analysis of late
      gene changes suggested roles for the transcription factor NF-kappaB and
      interferon signaling. Mice lacking the inhibitor of NF-kappaB (IkappaB) kinase
      (IKK) kinase TAK1 underwent normal positive selection but exhibited a specific
      block in functional maturation. NF-kappaB signaling provided protection from
      death mediated by the cytokine TNF and was required for proliferation and
      emigration. The interferon signature was independent of NF-kappaB; however,
      thymocytes deficient in the interferon-alpha (IFN-alpha) receptor IFN-alphaR
      showed reduced expression of the transcription factor STAT1 and phenotypic
      abnormality but were able to proliferate. Thus, both NF-kappaB and tonic
      interferon signals are involved in the final maturation of thymocytes into naive
      T cells. 

PMID- 27043412
TI  - TCR signal strength controls thymic differentiation of discrete proinflammatory
      gammadelta T cell subsets.
AB  - The mouse thymus produces discrete gammadelta T cell subsets that make either
      interferon-gamma (IFN-gamma) or interleukin 17 (IL-17), but the role of the T
      cell antigen receptor (TCR) in this developmental process remains controversial.
      Here we show that Cd3g(+/-) Cd3d(+/-) (CD3 double-haploinsufficient (CD3DH)) mice
      have reduced TCR expression and signaling strength on gammadelta T cells. CD3DH
      mice had normal numbers and phenotypes of alphabeta thymocyte subsets, but
      impaired differentiation of fetal Vgamma6(+) (but not Vgamma4(+)) IL-17-producing
      gammadelta T cells and a marked depletion of IFN-gamma-producing CD122(+)
      NK1.1(+) gammadelta T cells throughout ontogeny. Adult CD3DH mice showed reduced
      peripheral IFN-gamma(+) gammadelta T cells and were resistant to experimental
      cerebral malaria. Thus, TCR signal strength within specific thymic developmental
      windows is a major determinant of the generation of proinflammatory gammadelta T
      cell subsets and their impact on pathophysiology.

PMID- 27043413
TI  - Acidic chitinase primes the protective immune response to gastrointestinal
      nematodes.
AB  - Acidic mammalian chitinase (AMCase) is known to be induced by allergens and
      helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we
      show that AMCase deficiency reduced the number of group 2 innate lymphoid cells
      during allergen challenge but was not required for establishment of type 2
      inflammation in the lung in response to allergens or helminths. In contrast,
      AMCase-deficient mice showed a profound defect in type 2 immunity following
      infection with the chitin-containing gastrointestinal nematodes Nippostrongylus
      brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was
      associated with reduced mucus production and decreased intestinal expression of
      the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+)
      dendritic cells, which regulate T cell homing, were also reduced in mesenteric
      lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a
      critical initiator of protective type 2 responses to intestinal nematodes but is
      largely dispensable for allergic responses in the lung. 

PMID- 27043415
TI  - [Effects of Complex Versus Block Strength Training on the Athletic Performance of
      Elite Youth Soccer Players].

PMID- 27043414
TI  - S6K-STING interaction regulates cytosolic DNA-mediated activation of the
      transcription factor IRF3.
AB  - Cytosolic DNA-mediated activation of the transcription factor IRF3 is a key event
      in host antiviral responses. Here we found that infection with DNA viruses
      induced interaction of the metabolic checkpoint kinase mTOR downstream effector
      and kinase S6K1 and the signaling adaptor STING in a manner dependent on the DNA
      sensor cGAS. We further demonstrated that the kinase domain, but not the kinase
      function, of S6K1 was required for the S6K1-STING interaction and that the TBK1
      critically promoted this process. The formation of a tripartite S6K1-STING-TBK1
      complex was necessary for the activation of IRF3, and disruption of this
      signaling axis impaired the early-phase expression of IRF3 target genes and the
      induction of T cell responses and mucosal antiviral immunity. Thus, our results
      have uncovered a fundamental regulatory mechanism for the activation of IRF3 in
      the cytosolic DNA pathway. 

PMID- 27043416
TI  - Prenatal Education of Parents About Newborn Screening and Residual Dried Blood
      Spots: A Randomized Clinical Trial.
AB  - IMPORTANCE: Research clearly indicates that current approaches to newborn blood
      spot screening (NBS) education are ineffective. Incorporating NBS education into
      prenatal care is broadly supported by lay and professional opinion. OBJECTIVE: To
      determine the efficacy and effect of prenatal education about newborn screening
      and use of residual dried blood spots (DBS) in research on parental knowledge,
      attitudes, and behaviors. DESIGN, SETTING, AND PARTICIPANTS: A randomized
      clinical trial of prenatal educational interventions, with outcomes measured by
      survey at 2 to 4 weeks postpartum. Participants were recruited from obstetric
      clinics in Salt Lake City, Utah; San Francisco, California; and the Bronx, New
      York. Eligible women were English- or Spanish-speaking adults and did not have a
      high-risk pregnancy. A total of 901 women were enrolled. Participants who
      completed the follow-up survey included 212 women in the usual care group (70%
      retention), 231 in the NBS group (77% retention), and 221 women in the NBS + DBS
      group (75% retention). Those who completed the survey were similar across the 3
      groups with respect to age, ethnicity, race, education, marital status, income,
      obstetric history, and language. INTERVENTIONS: Participants were randomized into
      1 of 3 groups: usual care (n = 305), those viewing an NBS movie and brochure (n =
      300), and those viewing both the NBS and DBS movies and brochures (n = 296). MAIN
      OUTCOMES AND MEASURES: Two to four weeks postpartum, women completed a 91-item
      survey by telephone, addressing knowledge, attitudes, and behavior with respect
      to opting out of NBS or DBS for their child. RESULTS: A total of 901 women (mean
      age, 31 years) were randomized and 664 completed the follow-up survey. The total
      correct responses on the knowledge instrument in regard to NBS were 69% in the
      usual care group, 79% in the NBS group, and 75% in the NBS + DBS group, a
      significant between-group difference (P < .05). Although all groups showed strong
      support for NBS, the percentage of women who were "very supportive" was highest
      in the NBS group (94%), followed by the NBS + DBS group (86%) and was lowest in
      the usual care group (73%) (P < .001). The interventions were not associated with
      decisions to decline newborn screening or withdraw residual DBS. Nine women
      stated that they had declined NBS (all the usual care group; P < .001). With
      respect to DBS, 5 participants indicated that they contacted the health
      department to have their child's sample withdrawn after testing: 3 in the NBS +
      DBS group and 2 in the usual care group (P = .25). CONCLUSIONS AND RELEVANCE:
      Educational interventions can be implemented in the prenatal clinic, using
      multimedia tools and electronic platforms. Prenatal education is effective in
      increasing postnatal knowledge and support for these programs. These results are
      relevant to other contexts in which residual clinical specimens and data are used
      for research purposes. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT02676245.

PMID- 27043418
TI  - Solid Renal Cell Carcinomas With an Attenuation Similar to That of Water on
      Unenhanced CT.

PMID- 27043417
TI  - Legacy effects of short-term intentional weight loss on total body and thigh
      composition in overweight and obese older adults.
AB  - OBJECTIVE: Weight regain following intentional weight loss may negatively impact
      body composition, accelerating fat regain and increasing risk of physical
      disability. The purpose of this study was to compare long-term changes in whole
      body and thigh composition in obese older adults who intentionally lost and then
      partially regained weight to obese older adults who remained weight stable.
      SUBJECTS/METHODS: This pilot study analyzed total body (dual-energy X-ray
      absorptiometry (DXA)) and thigh (computed tomography (CT)) composition data
      collected from 24 older (65-79 years) adults 18 months after completion of a 5
      month randomized trial that compared resistance training alone (RT) with RT plus
      caloric restriction (RT+CR). RESULTS: Mean loss of body mass in the RT+CR group
      (n=13) was 7.1+/-2.4 kg during the 5-month intervention (74% fat mass; 26% lean
      mass; all P<0.01), whereas RT (n=11) remained weight stable (+0.3+/-1.8 kg;
      P=0.64). Differential group effects were observed for all DXA and CT body
      composition measures at 5 months (all P?0.01); however, by 23 months, group
      differences persisted only for total body (RT+CR: 81.6+/-10.0 kg vs RT: 88.5+/
      14.9 kg; P=0.03) and lean (RT+CR: 50.8+/-9.3 kg vs RT: 54.4+/-12.0 kg; P<0.01)
      mass. All RT+CR participants regained weight from 5 to 23 months (mean
      gain=+4.8+/-2.6 kg; P<0.01). Total fat mass and all thigh fat volumes increased,
      whereas thigh muscle volume decreased, during the postintervention follow-up in
      RT+CR (all P?0.01). In the RT group, body mass did not change from 5 to 23 months
      (-0.2+/-0.9 kg; P=0.87). Decreased total thigh volume, driven by the loss of
      thigh muscle volume, were the only postintervention body composition changes
      observed in the RT group (both P<0.04). CONCLUSIONS: Short-term body composition
      benefits of an RT+CR intervention may be lost within 18 months after completion
      of the intervention.

PMID- 27043419
TI  - Novel chemoselective (18)F-radiolabeling of thiol-containing biomolecules under
      mild aqueous conditions.
AB  - We report a novel prosthetic group based on a heterocyclic methylsulfone
      derivative for the rapid, stable, and chemoselective (18)F-labeling of thiol
      containing (bio)molecules under mild aqueous reaction conditions. Compared to
      established maleimide approaches, the new methodology displays some clear
      advantages for imaging probe development. 

PMID- 27043420
TI  - Transcriptome analysis of Mastomys natalensis papillomavirus in productive
      lesions after natural infection.
AB  - Mastomys coucha, an African rodent, is a useful animal model of papillomavirus
      infection, as it develops both premalignant and malignant skin tumors as a
      consequence of a persistent infection with Mastomys natalensis papillomavirus
      (MnPV). In this study, we mapped the MnPV transcriptome in productive lesions by
      both classical molecular techniques and high-throughput RNA sequencing.
      Combination of these methods revealed a complex and comprehensive transcription
      map, with novel splicing events not described in other papillomaviruses.
      Furthermore, these splicing occurrences could potentially lead to the expression
      of novel E2, E1?E4, E7 and L2 isoforms. Expression level estimation of each
      transcript showed that late-region mRNAs considerably outnumber early
      transcripts, with species coding for L1 and E1?E4 being the most abundant. In
      summary, the full transcription map assembled in this study will allow us to
      further understand MnPV gene expression and the mechanisms that lead to natural
      tumour development.

PMID- 27043421
TI  - Superhydrophobic and Superoleophilic Micro-Wrinkled Reduced Graphene Oxide as a
      Highly Portable and Recyclable Oil Sorbent.
AB  - The potential of superhydrophobic and superoleophilic microwrinkled reduced
      graphene oxide (MWrGO) structures is here demonstrated for oil spill cleanup. The
      impact of the thickness of MWrGO films on the sorption performance of three
      different oils was investigated. Water contact angles across the MWrGO surfaces
      were found to exceed 150 degrees , while oil could be easily absorbed by the
      microwrinkled structures of MWrGO within seconds after contact. Although the oil
      surface diffusion rate was not found to be dependent on the thickness of the
      graphene oxide films, the oil sorption capacity was the largest with the thinner
      MWrGO films due to the high surface area resulting from their fine surface
      texture. Furthermore, the composite films can be repeatedly used for at least 20
      oil sorption-removal cycles without any notable loss in selectivity and uptake
      capacity. These MWrGO/elastomer composite films could be applied as a potential
      candidate material for future oil spill cleanup. 

PMID- 27043422
TI  - Realizing HOPE: The Ethics of Organ Transplantation From HIV-Positive Donors.
AB  - The HIV Organ Policy Equity (HOPE) Act now allows transplantation of organs from
      HIV-positive living and deceased donors to HIV-positive individuals with end
      stage organ disease in the United States. Although clinical experience with such
      transplants is limited to a small number of deceased-donor kidney transplants
      from HIV-positive to HIV-positive persons in South Africa, unprecedented HIV
      positive-to-HIV-positive liver transplantations and living-donor kidney
      transplantations are also now on the horizon. Initially, all HIV-positive-to-HIV
      positive transplantations will occur under research protocols with safeguards and
      criteria mandated by the National Institutes of Health. Nevertheless, this
      historic change brings ethical opportunities and challenges. For HIV-positive
      individuals needing an organ transplant, issues of access, risk, and consent must
      be considered. For potential HIV-positive donors, there are additional ethical
      challenges of privacy, fairness, and the right to donate. Careful consideration
      of the ethical issues involved is critical to the safe and appropriate evaluation
      of this novel approach to transplantation.

PMID- 27043423
TI  - Coronary Artery Variants and Anomalies in Patients With Bicuspid Aortic Valve.
AB  - PURPOSE: The aim of this study was to assess the prevalence of variants and
      anomalies of the coronary arteries in patients with bicuspid aortic valve (BAV)
      and compare it with patients with tricuspid aortic valve (TAV). MATERIALS AND
      METHODS: A total of 428 patients (193 with BAV, 235 with TAV) who underwent
      coronary computed tomography angiography were analyzed. RESULTS: The right
      coronary artery was dominant in 360 (84.1%) cases, including 157 (81.34%) with
      BAV and 203 (86.38%) with TAV. Left dominance was observed in 51 (11.9%)
      patients, including 30 (15.54%) with BAV 21 (8.93%) with TAV (P=0.08), and
      codominance in 17 (4%). The mean length of the left main coronary artery (LMCA)
      in patients with BAV was 10.45+/-6.93 versus 12.02+/-5.12 mm in those with TAV
      (P=0.008). The absence of the LMCA with separate origins of the left artery
      descending and the left circumflex artery was observed in 18 cases, 14/193 (7.3%)
      with BAV and 4/235 (1.7%) with TAV (P=0.004). The ramus intermedius was present
      in 50 (11.7%) patients, 29 with BAV (15%) and 21 with TAV (8.9%) (P=0.05).
      Coronary artery anomalies were observed in 2.1% of all patients (5/193 with BAV
      vs. 4/235 with TAV, P=0.5). CONCLUSIONS: The prevalence of anomalies of coronary
      arteries was similar in both groups. Patients with BAV had a higher incidence of
      the absence of the LMCA and the presence of the ramus intrermedius. The mean
      length of the LMCA in patients with BAV was shorter than in patients with TAV.
      There was a trend for a higher incidence of left dominance in patients with BAV
      compared to those with TAV, but did not reach statistical significance.

PMID- 27043424
TI  - Nondiagnostic Computed Tomography-guided Percutaneous Lung Biopsies Are More
      Likely When Infection Is Suspected.
AB  - PURPOSE: The purpose of this study was to assess the incidence of nondiagnostic
      computed tomography-guided lung biopsy results, stratified by biopsy indication,
      and determine the final diagnosis in such cases. MATERIALS AND METHODS: Following
      institutional review board approval, pathology results from CT-guided lung
      biopsies over a 5-year period at 2 institutions were categorized as diagnostic or
      nondiagnostic. Each biopsy's indication was categorized as being for a lesion
      considered likely to be cancer, infection, or uncertain. For all nondiagnostic
      biopsies, the medical chart was reviewed to determine the final clinical
      diagnosis. RESULTS: A total of 660 biopsies were evaluated, 139 (21%) of which
      were nondiagnostic. Of these 139 patients, the final clinical diagnosis was
      infection in 37%, cancer in 30%, and a benign noninfectious diagnosis in 10%; 23%
      remained undiagnosed at last available follow-up. Among the patients in whom
      there was a high pretest suspicion for cancer, 13% were nondiagnostic, 45% of
      which were cancer and 27% were infection. Among biopsies of lesions with pretest
      probability for both cancer and infection, 51% were nondiagnostic; on clinical
      follow-up these were determined to be infection in 34% and cancer in 14%. When
      there was high pretest suspicion for infection, 73% were nondiagnostic, of which
      13% were cancer on clinical follow-up, and 88% were infection. The rate of
      nondiagnostic biopsies was statistically significantly different (P<0.001) among
      the 3 groups. CONCLUSIONS: Nondiagnostic biopsies are common and occur most
      frequently when there is a moderate or high pretest suspicion for infection.
      Among all nondiagnostic biopsies, regardless of indication, cancer and infection
      were diagnosed on follow-up in similar proportions.

PMID- 27043425
TI  - Idiopathic Pulmonary Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and
      is associated with a very poor prognosis. IPF manifests histopathologically as
      usual interstitial pneumonia (UIP) and as subpleural and basal predominant
      reticulation with honeycombing on high-resolution computed tomography (HRCT) of
      the chest. When a high-confidence radiologic diagnosis of UIP is made on HRCT,
      surgical biopsy is rarely required. Therefore, radiologists should recognize a
      UIP pattern on HRCT as well as recognize other patterns of fibrosing lung disease
      such as nonspecific interstitial pneumonia or chronic hypersensitivity
      pneumonitis, both of which can be mistaken for UIP. This article reviews the
      clinical, CT, and histopathologic features of IPF, discusses the impact of CT
      findings on prognosis, and describes complications associated with IPF. 

PMID- 27043426
TI  - Comparison of Image Processing Techniques for Nonviable Tissue Quantification in
      Late Gadolinium Enhancement Cardiac Magnetic Resonance Images.
AB  - PURPOSE: The aim of this study was to compare the performance of quantitative
      methods, either semiautomated or automated, for left ventricular (LV) nonviable
      tissue analysis from cardiac magnetic resonance late gadolinium enhancement (CMR
      LGE) images. MATERIALS AND METHODS: The investigated segmentation techniques
      were: (i) n-standard deviations thresholding; (ii) full width at half maximum
      thresholding; (iii) Gaussian mixture model classification; and (iv) fuzzy c-means
      clustering. These algorithms were applied either in each short axis slice (single
      slice approach) or globally considering the entire short-axis stack covering the
      LV (global approach). CMR-LGE images from 20 patients with ischemic
      cardiomyopathy were retrospectively selected, and results from each technique
      were assessed against manual tracing. RESULTS: All methods provided comparable
      performance in terms of accuracy in scar detection, computation of local
      transmurality, and high correlation in scar mass compared with the manual
      technique. In general, no significant difference between single-slice and global
      approach was noted. The reproducibility of manual and investigated techniques was
      confirmed in all cases with slightly lower results for the nSD approach.
      CONCLUSIONS: Automated techniques resulted in accurate and reproducible
      evaluation of LV scars from CMR-LGE in ischemic patients with performance similar
      to the manual technique. Their application could minimize user interaction and
      computational time, even when compared with semiautomated approaches.

PMID- 27043427
TI  - Neurologist Comfort in the Use of Next-Generation Sequencing Diagnostics: Current
      State and Future Prospects.

PMID- 27043428
TI  - The effect of external magnetic fields on the catalytic activity of Pd
      nanoparticles in Suzuki cross-coupling reactions.
AB  - Pd nanoparticles supported on Co3[Co(CN)6]2 nanoparticles (marked as
      Pd@Co3[Co(CN)6]2 nanoparticles) were prepared as catalysts for the Suzuki cross
      coupling reaction under external magnetic fields (MFs). It is shown that a weak
      external MF can increase the rate of the Suzuki cross-coupling reaction at room
      temperature, and with the increase of the strength of external MFs the reaction
      rate also increased. At 30  degrees C, the yield was increased by nearly 50%
      under a 0.5 T external MF after 24 hours compared to that without a MF applied.
      Theoretical calculations revealed that the adsorption energy changed from -1.07
      to -1.12 eV in the presence of MFs, which increased by 5% compared with the
      absence of MFs, leading to a lower total energy of the adsorption system, which
      is beneficial to the reaction. From the analysis of the partial density states,
      it could be seen that the 2p orbital of the carbon atom in bromobenzene and the
      4d orbital of the Pd atom overlap more closely in the presence of MFs, which is
      beneficial for the electron transfer from the Pd substrate to the bromobenzene
      molecule. This study is helpful in understanding the interaction between MFs and
      catalysts and regulating the process of catalytic reactions via MFs. 

PMID- 27043430
TI  - Perovskite Nanoparticle-Sensitized Ga2O3 Nanorod Arrays for CO Detection at High
      Temperature.
AB  - Noble metal nanoparticles are extensively used for sensitizing metal oxide
      chemical sensors through the catalytic spillover mechanism. However, due to earth
      scarcity and high cost of noble metals, finding replacements presents a great
      economic benefit. Besides, high temperature and harsh environment sensor
      applications demand material stability under conditions approaching thermal and
      chemical stability limits of noble metals. In this study, we employed thermally
      stable perovskite-type La(0.8)Sr(0.2)FeO3 (LSFO) nanoparticle surface decoration
      on Ga2O3 nanorod array gas sensors and discovered an order of magnitude enhanced
      sensitivity to carbon monoxide at 500  degrees C. The LSFO nanoparticle catalysts
      was of comparable performance to that achieved by Pt nanoparticles, with a much
      lower weight loading than Pt. Detailed electron microscopy and X-ray
      photoelectron spectroscopy studies suggested the LSFO nanoparticle sensitization
      effect is attributed to a spillover-like effect associated with the gas-LSFO
      Ga2O3 triple-interfaces that spread the negatively charged surface oxygen ions
      from LSFO nanoparticles surfaces over to beta-Ga2O3 nanorod surfaces with faster
      surface CO oxidation reactions.

PMID- 27043429
TI  - Simulation-Based Approaches for Determining Membrane Permeability of Small
      Compounds.
AB  - Predicting the rate of nonfacilitated permeation of solutes across lipid bilayers
      is important to drug design, toxicology, and signaling. These rates can be
      estimated using molecular dynamics simulations combined with the inhomogeneous
      solubility-diffusion model, which requires calculation of the potential of mean
      force and position-dependent diffusivity of the solute along the transmembrane
      axis. In this paper, we assess the efficiency and accuracy of several methods for
      the calculation of the permeability of a model DMPC bilayer to urea, benzoic
      acid, and codeine. We compare umbrella sampling, replica exchange umbrella
      sampling, adaptive biasing force, and multiple-walker adaptive biasing force for
      the calculation of the transmembrane PMF. No definitive advantage for any of
      these methods in their ability to predict the membrane permeability coefficient
      Pm was found, provided that a sufficiently long equilibration is performed. For
      diffusivities, a Bayesian inference method was compared to a generalized Langevin
      method, both being sensitive to chosen parameters and the slow relaxation of
      membrane defects. Agreement within 1.5 log units of the computed Pm with
      experiment is found for all permeants and methods. Remaining discrepancies can
      likely be attributed to limitations of the force field as well as slowly relaxing
      collective movements within the lipid environment. Numerical calculations based
      on model profiles show that Pm can be reliably estimated from only a few data
      points, leading to recommendations for calculating Pm from simulations.

PMID- 27043431
TI  - Chromium-Catalyzed Asymmetric Dearomatization Addition Reactions of Halomethyl
      Heteroarenes.
AB  - The first asymmetric dearomatization addition reaction of halomethyl arenes
      including benzofuran and benzothiophene was enabled by chromium catalysis. A
      variety of aldehydes served as suitable electrophiles under mild reaction
      conditions. Molecular complexities are quickly increased in a highly diastereo-
      and enantioselective manner. 

PMID- 27043432
TI  - Cholesterol trials and mortality.
AB  - An overview of clinical trials can reveal a class effect on mortality that is not
      apparent from individual trials. Most large trials of lipid pharmacotherapy are
      not powered to detect differences in mortality and instead assess efficacy with
      composite cardiovascular endpoints. We illustrate the importance of all-cause
      mortality data by comparing survival in three different sets of the larger
      controlled lipid trials that underpin meta-analyses. These trials are for
      fibrates and statins. Fibrate treatment in five of the six main trials was
      associated with a decrease in survival, one fibrate trial showed a non
      significant reduction in mortality that can be explained by a different target
      population. In secondary prevention, statin treatment increased survival in all
      five of the main trials, absolute mean increase ranged from 0.43% to 3.33%, the
      median change was 1.75%, which occurred in the largest trial. In primary
      prevention, statin treatment increased survival in six of the seven main trials,
      absolute mean change in survival ranged from -0.09% to 0.89%, median 0.49%.
      Composite safety endpoints are rare in these trials. The failure to address
      composite safety endpoints in most lipid trials precludes a balanced summary of
      risk-benefit when a composite has been used for efficacy. Class effects on
      survival provide informative summaries of the risk-benefit of lipid
      pharmacotherapy. We consider that the presentation of key mortality/survival data
      adds to existing meta-analyses to aid personal treatment decisions.

PMID- 27043433
TI  - Selenium Digestibility and Bioactivity in Dogs: What the Can Can, the Kibble
      Can't.
AB  - There is a growing concern for the long-term health effects of selenium (Se) over
      or underfeeding. The efficiency of utilization of dietary Se is subject to many
      factors. Our study in dogs evaluated the effect of diet type (canned versus
      kibble) and dietary protein concentration on Se digestibility and bioactivity.
      Canned and kibble diets are commonly used formats of dog food, widely ranging in
      protein concentration. Twenty-four Labrador retrievers were used and four canned
      and four kibble diets were selected with crude protein concentrations ranging
      from 10.1 to 27.5 g/MJ. Crude protein concentration had no influence on the
      digestibility of Se in either canned or kibble diets, but a lower Se
      digestibility was observed in canned compared to kibble diets. However, the
      biological activity of Se, as measured by whole blood glutathione peroxidase, was
      higher in dogs fed the canned diets than in dogs fed the kibble diets and
      decreased with increasing crude protein intake. These results indicate that
      selenium recommendations in dog foods need to take diet type into account. 

PMID- 27043435
TI  - Two Distinct Transitions in Cu(x)InS2 Quantum Dots. Bandgap versus Sub-Bandgap
      Excitations in Copper-Deficient Structures.
AB  - Cu-deficient CuInS2 quantum dots (QDs) synthesized by varying the [Cu]:[In] ratio
      allow modulation of optical properties as well as identification of the radiative
      emission pathways. Absorption and emission spectral features showed a strong
      dependence on the [Cu]:[In] ratio of CuxInS2 QDs, indicating two independent
      optical transitions. These effects are pronounced in transient absorption
      spectra. The bleaching of band edge absorption and broad tail absorption bands in
      the subpicosecond-nanosecond time scale provide further evidence for the dual
      optical transitions. The recombination process as monitored by photoemission
      decay indicated the involvement of surface traps in addition to the bandgap and
      sub-bandgap transitions. Better understanding of the origin of the optical
      transitions and their influence on the photodynamics will enable utilization of
      ternary semiconductor quantum dots in display and photovoltaic devices. 

PMID- 27043434
TI  - Pancreatic beta-Cell Dysfunction in Diet-Induced Obese Mice: Roles of AMP-Kinase,
      Protein Kinase Cepsilon, Mitochondrial and Cholesterol Metabolism, and
      Alterations in Gene Expression.
AB  - Diet induced obese (DIO) mice can be stratified according to their weight gain in
      response to high fat diet as low responders (LDR) and high responders (HDR). This
      allows the study of beta-cell failure and the transitions to prediabetes (LDR)
      and early diabetes (HDR). C57BL/6N mice were fed for 8 weeks with a normal chow
      diet (ND) or a high fat diet and stratified as LDR and HDR. Freshly isolated
      islets from ND, LDR and HDR mice were studied ex-vivo for mitochondrial
      metabolism, AMPK activity and signalling, the expression and activity of key
      enzymes of energy metabolism, cholesterol synthesis, and mRNA profiling. Severely
      compromised glucose-induced insulin secretion in HDR islets, as compared to ND
      and LDR islets, was associated with suppressed AMP-kinase activity. HDR islets
      also showed reduced acetyl-CoA carboxylase activity and enhanced activity of 3
      hydroxy-3-methylglutaryl-CoA reductase, which led respectively to elevated fatty
      acid oxidation and increased cholesterol biosynthesis. HDR islets also displayed
      mitochondrial membrane hyperpolarization and reduced ATP turnover in the presence
      of elevated glucose. Expression of protein kinase Cepsilon, which reduces both
      lipolysis and production of signals for insulin secretion, was elevated in DIO
      islets. Genes whose expression increased or decreased by more than 1.2-fold were
      minor between LDR and ND islets (17 differentially expressed), but were prominent
      between HDR and ND islets (1508 differentially expressed). In HDR islets,
      particularly affected genes were related to cell cycle and proliferation, AMPK
      signaling, mitochondrial metabolism and cholesterol metabolism. In conclusion,
      chronically reduced AMPK activity, mitochondrial dysfunction, elevated
      cholesterol biosynthesis in islets, and substantial alterations in gene
      expression accompany beta-cell failure in HDR islets. The beta-cell compensation
      process in the prediabetic state (LDR) is largely independent of transcriptional
      adaptive changes, whereas the transition to early diabetes (HDR) is associated
      with major alterations in gene expression. 

PMID- 27043436
TI  - Efficient Translation of Pelargonium line pattern virus RNAs Relies on a TED-Like
      3'-Translational Enhancer that Communicates with the Corresponding 5'-Region
      through a Long-Distance RNA-RNA Interaction.
AB  - Cap-independent translational enhancers (CITEs) have been identified at the 3'
      terminal regions of distinct plant positive-strand RNA viruses belonging to
      families Tombusviridae and Luteoviridae. On the bases of their structural and/or
      functional requirements, at least six classes of CITEs have been defined whose
      distribution does not correlate with taxonomy. The so-called TED class has been
      relatively under-studied and its functionality only confirmed in the case of
      Satellite tobacco necrosis virus, a parasitic subviral agent. The 3'-untranslated
      region of the monopartite genome of Pelargonium line pattern virus (PLPV), the
      recommended type member of a tentative new genus (Pelarspovirus) in the family
      Tombusviridae, was predicted to contain a TED-like CITE. Similar CITEs can be
      anticipated in some other related viruses though none has been experimentally
      verified. Here, in the first place, we have performed a reassessment of the
      structure of the putative PLPV-TED through in silico predictions and in vitro
      SHAPE analysis with the full-length PLPV genome, which has indicated that the
      presumed TED element is larger than previously proposed. The extended
      conformation of the TED is strongly supported by the pattern of natural sequence
      variation, thus providing comparative structural evidence in support of the
      structural data obtained by in silico and in vitro approaches. Next, we have
      obtained experimental evidence demonstrating the in vivo activity of the PLPV-TED
      in the genomic (g) RNA, and also in the subgenomic (sg) RNA that the virus
      produces to express 3'-proximal genes. Besides other structural features, the
      results have highlighted the key role of long-distance kissing-loop interactions
      between the 3'-CITE and 5'-proximal hairpins for gRNA and sgRNA translation.
      Bioassays of CITE mutants have confirmed the importance of the identified 5'-3'
      RNA communication for viral infectivity and, moreover, have underlined the strong
      evolutionary constraints that may operate on genome stretches with both
      regulatory and coding functions. 

PMID- 27043437
TI  - Sperm Chromatin Immaturity Observed in Short Abstinence Ejaculates Affects DNA
      Integrity and Longevity In Vitro.
AB  - BACKGROUND: The influence of ejaculatory abstinence (EA) on semen parameters and
      subsequent reproductive outcome is still debatable; hence understanding the
      impact of EA on sperm structural and functional integrity may provide a valuable
      information on predicting successful clinical outcome. OBJECTIVE: To understand
      the influence of EA on sperm chromatin maturity, integrity, longevity and global
      methylation status. METHODS: This experimental prospective study included 76
      ejaculates from 19 healthy volunteers who provided ejaculates after observing 1,
      3, 5 and 7 days of abstinence. Sperm chromatin maturity, DNA integrity and global
      methylation status were assessed in the neat ejaculate. Sperm motility, DNA
      integrity and longevity were assessed in the processed fraction of the fresh and
      frozen-thawed ejaculates to determine their association with the length of EA.
      RESULTS: Spermatozoa from 1 day ejaculatory abstinence (EA-1) displayed
      significantly higher level of sperm chromatin immaturity in comparison to EA-3 (P
      < 0.05) and EA-5 (P < 0.01) whereas; the number of 5-methyl cytosine
      immunostained spermatozoa did not vary significantly across groups. On the other
      hand, in vitro incubation of processed ejaculate from EA-1 resulted in
      approximately 20 and 40 fold increase in the DNA fragmented spermatozoa at the
      end of 6 and 24h respectively (P < 0.01-0.001). CONCLUSION: Use of short-term EA
      for therapeutic fertilization would be a clinically valuable strategy to improve
      the DNA quality. However, use of such spermatozoa after prolonged incubation in
      vitro should be avoided as it can carry a substantial risk of transmitting DNA
      fragmentation to the oocytes.

PMID- 27043438
TI  - The Effect of Religion on Candidate Preference in the 2008 and 2012 Republican
      Presidential Primaries.
AB  - Thanks to the work of politics and religion scholars, we now know a lot about the
      relationship between religion and voting in American presidential general
      elections. However, we know less about the influence of religion on individual
      vote choice in presidential primaries. This article fills that gap by exploring
      the relationship between religion and candidate preference in the 2008 and 2012
      Republican primaries. Using pre-Super Tuesday surveys conducted by the Pew
      Research Center, I find that the Republican candidate who most explicitly
      appealed to religious voters (Mike Huckabee in 2008 and Rick Santorum in 2012)
      was the preferred candidate of Republican respondents who attended religious
      services at the highest levels, and that as attendance increased, so did the
      likelihood of preferring that candidate. I also find that identification as a
      born again Christian mattered to candidate preference. Specifically, born again
      Christians were more likely than non-born again Christians to prefer Huckabee to
      Mitt Romney, John McCain and Ron Paul in 2008, and Santorum to Romney in 2012.
      Although ideology was not the primary subject of this article, I find that
      ideology was also a statistically significant predictor of Republican candidate
      preference in both 2008 and 2012. This robust finding reinforces scholars' prior
      work on the importance of ideology in explaining presidential primary vote
      choice. The overall findings of the paper provide evidence that religion
      variables can add to our understanding of why voters prefer one candidate over
      another in presidential primaries. 

PMID- 27043439
TI  - Variations in Postpartum Hemorrhage Management among Midwives: A National
      Vignette-Based Study.
AB  - OBJECTIVE: To assess variations in adherence to guidelines for management of
      postpartum hemorrhage (PPH) among midwives. METHODS: A multicentre vignette-based
      study was e-mailed to a random sample of midwives from 145 maternity units in
      France. They were asked to describe how they would manage the PPH described in 2
      case-vignettes. These previously validated case-vignettes described 2 different
      scenarios for severe PPH. Vignette 1 described a typical immediate, severe PPH
      and vignette 2 a less typical case of severe but gradual PPH. They were
      constructed in 3 successive steps and included multiple-choice questions
      proposing several types of clinical practice options at each step. An expert
      consensus defined 14 criteria for assessing adherence to guidelines issued by the
      French College of Obstetricians and Gynecologists in 2004 in the midwives'
      responses. We analyzed the number of errors among the 14 criteria to quantify the
      level of adherence. RESULTS: We obtained 450 complete responses from midwives
      from 87 maternity units. The rate of complete adherence (no error for any of the
      14 criteria) was low: 25.1% in vignette 1 and 4.2% in vignette 2. The error rate
      was higher for pharmacological management, especially oxytocin use, than for non
      pharmacological management and communication-monitoring-investigation. Adherence
      to guidelines varied substantially between and within maternity units, as well as
      between the vignettes for the same midwives. CONCLUSION: Reponses to case
      vignettes demonstrated substantial variations in PPH management and especially
      individual variations in adherence to guidelines. Midwives should participate in
      continuous and individualized training.

PMID- 27043440
TI  - Imperatorin inhibits the expression of alpha-hemolysin in Staphylococcus aureus
      strain BAA-1717 (USA300).
AB  - Both community-associated and hospital-acquired infections with methicillin
      resistant Staphylococcus aureus (MRSA) have been increasingly reported around the
      world in the past 20 years. In 2006, the Centers for Disease Control and
      Prevention reported that 64 % of MRSA isolates were of the USA300 clonal type in
      infected patients in USA. The aim of our study was to estimate the in vitro
      effect of imperatorin on MRSA strain BAA-1717 (USA300). The effects of
      imperatorin on alpha-hemolysin (Hla) production, when strain BAA-1717 was co
      cultured with sub-inhibitory concentrations of imperatorin, were analysed using
      susceptibility testing, hemolysis assays, western blotting and real-time PCR.
      Live/Dead analysis and cytotoxicity assays were employed to examine the
      protective effect of imperatorin against the strain BAA-1717-mediated injury of
      human alveolar epithelial cells (A549). The results showed that imperatorin has
      no anti-S. aureus activity at the tested concentrations in vitro. However,
      imperatorin can observably inhibit the production of Hla in culture supernatants
      and reduce the transcriptional levels of hla (the gene encoding Hla) and arg (the
      accessory gene regulator). Imperatorin prevented Hla-mediated A549 epithelial
      cell injury in a co-culture system. In conclusion, our results suggested that
      imperatorin has the potential to be developed as a new anti-virulence drug
      candidate for managing S. aureus infection. 

PMID- 27043441
TI  - Dissymmetric Bis(dipyrrinato)zinc(II) Complexes: Rich Variety and Bright Red to
      Near-Infrared Luminescence with a Large Pseudo-Stokes Shift.
AB  - Bis(dipyrrinato)metal(II) and tris(dipyrrinato)metal(III) complexes have been
      regarded as much less useful luminophores than their boron difluoride
      counterparts (4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes, BODIPYs), especially
      in polar solvent. We proposed previously that dissymmetry in such metal complexes
      (i.e., two different dipyrrinato ligands in one molecule) improves their
      fluorescence quantum efficiencies. In this work, we demonstrate the universality
      and utility of our methodology by synthesizing eight new dissymmetric
      bis(dipyrrinato)zinc(II) complexes and comparing them with corresponding
      symmetric complexes. Single-crystal X-ray diffraction analysis, (1)H and (13)C
      NMR spectroscopy, and high-resolution mass spectrometry confirm the retention of
      dissymmetry in both solution and solid states. The dissymmetric complexes all
      show greater photoluminescence (PL) quantum yields (phiPL) than the corresponding
      symmetric complexes, allowing red to near-infrared emissions with large pseudo
      Stokes shifts. The best performance achieves a maximum PL wavelength of 671 nm, a
      pseudo-Stokes shift of 5400 cm(-1), and phiPL of 0.62-0.72 in toluene (dielectric
      constant epsilons = 2.4), dichloromethane (epsilons = 9.1), acetone (epsilons =
      21.4), and ethanol (epsilons = 24.3). The large pseudo-Stokes shift is
      distinctive considering BODIPYs with small Stokes shifts (~500 cm(-1)), and the
      phiPL values are higher than or comparable to those of BODIPYs fluorescing at
      similar wavelengths. Electrochemistry and density functional theory calculations
      illustrate that frontier orbital ordering in the dissymmetric complexes meets the
      condition for efficient PL proposed in our theory.

PMID- 27043442
TI  - Polymer Nanoparticles Modified with Photo- and pH-Dual-Responsive Polypeptides
      for Enhanced and Targeted Cancer Therapy.
AB  - The cationic nature of cell penetrating peptides (CPPs) and their absence of cell
      selectivity restrains their applications in vivo. In this work, polymer
      nanoparticles (NPs) modified with photo- and pH-responsive polypeptides (PPPs)
      were successfully developed and respond to near-infrared (NIR) light illumination
      at the tumor site and a lowered tumor extracellular pH (pHe). In PPPs, the
      internalization function of CPPs (positively charged) is quenched by a pH
      sensitive inhibitory peptide (negatively charged), which is linked via a
      photocleavable group. Small interfering RNA (siRNA) was loaded into NPs by a
      double-emulsion technique. In vivo experiments included siRNA loading, cellular
      uptake, cell apoptosis, siRNA transfection, tumor targeting delivery, and the in
      vivo antitumor efficacy. Results showed that the prepared PPP-NPs could
      selectively accumulate at the tumor sites and internalized into the tumor cells
      by the NIR light illumination and the lowered pHe at the tumor site. These
      studies demonstrated that PPP-NPs are a promising carrier for future tumor gene
      delivery.

PMID- 27043443
TI  - Frailty.

PMID- 27043444
TI  - Epidemiology and clinical outcome of intraocular foreign bodies in Hong Kong: a
      13-year review.
AB  - The purpose of this study was to describe the epidemiology, visual outcome and
      prognostic factors of intraocular foreign body (IOFB) injuries in a tertiary
      centre in Hong Kong. A retrospective review of 21 eyes in 21 patients with IOFB
      that presented to United Christian Hospital from January 2001 to July 2014 was
      performed. IOFB represented 16 % of all open-globe traumas. There was a high male
      predominance (90 %). The mean age was 42. Work-related injuries (86 %) were the
      main cause, where only 10.5 % had eye protection. Hammering was the commonest
      mechanism of injury (43 %). Most IOFBs were metallic (67 %). The IOFB was found
      in the anterior segment in 31 % and posterior segment in 69 %. 57 % presented
      with an initial visual acuity of >=0.1, and up to 24 % of patients had an initial
      visual acuity of better than or equal to 0.5. Most cases (76 %) received prompt
      surgical intervention within 24 h, and there was a low (0 %) endophthalmitis
      rate. Forty-eight percent had an improvement in visual acuity, defined as final
      visual acuity more than or equal to 2 lines of improvement from initial visual
      acuity, and 48 % attained a final visual acuity of better than or equal to 0.5.
      One case underwent evisceration. A smaller IOFB size (<5 mm) was associated with
      a good final visual acuity of better than or equal to 0.5 (p = 0.048). It was
      also found that a posterior segment IOFB was more likely to give a final VA of
      less than 0.5 (p = 0.035). IOFB remains a significant complication of work
      related injuries in Hong Kong. This is the first local study that explores the
      epidemiology of IOFB injuries in Hong Kong. The favourable visual outcome and low
      endophthalmitis rate may be related to early removal of IOFB. Despite legal
      ordinances for mandatory eye protection, the uptake of eye protection was low.

PMID- 27043445
TI  - Possible interstellar formation of glycine through a concerted mechanism: a
      computational study on the reaction of CH2[double bond, length as m-dash]NH, CO2
      and H2.
AB  - Glycine being the simplest amino acid and also having significant astrobiological
      implications, has meant that intensive investigations have been carried out in
      the past, starting from its detection in the interstellar medium (ISM) to
      analysis of meteorites and cometary samples and laboratory synthesis, as well as
      computational studies on the possible reaction paths. In this present work
      quantum chemical calculations have been performed to investigate the possible
      interstellar formation of glycine via two different paths; (1) in a two-step
      process via a dihydroxy carbene intermediate and (2) through a one-step concerted
      mechanism, starting from reactants like CH2[double bond, length as m-dash]NH, CO,
      CO2, H2O and H2. For the two reactions representing the carbene route, it was
      observed that the formation of dihydroxy carbene from either CO + H2O or CO2 + H2
      is highly endothermic with large barrier heights, whereas the subsequent step of
      interaction of this carbene with CH2[double bond, length as m-dash]NH to give
      glycine is exothermic and the barrier is below the reactants. Based on this
      observation it is suggested that the formation of glycine via the carbene route
      is a least favourable or even unfavourable path. On the other hand, the two
      reactions CH2[double bond, length as m-dash]NH + CO + H2O and CH2[double bond,
      length as m-dash]NH + CO2 + H2 representing the concerted paths were found to be
      favourable in leading to the formation of glycine. After an extensive study on
      the first concerted reaction in our previous work (Phys. Chem. Chem. Phys., 2016,
      18, 375-381), in this work a detailed investigation has been carried out for the
      second concerted reaction, CH2[double bond, length as m-dash]NH + CO2 + H2, which
      can possibly lead to the interstellar formation of glycine. It was observed that
      this reaction proceeds through a large barrier and at the same time the
      transition state shows prominent hydrogen dynamics, indicating a tunnelling
      possibility for this reaction. Based on these observations the possible formation
      of glycine via this reaction in hot-cores and in cold interstellar clouds has
      been proposed. The cold-core possibility of this reaction is argued on the basis
      of the phenomenon of tunnelling assisted by a van der Waals' complex. 

PMID- 27043447
TI  - Self-Assembly of the Cyclic Lipopeptide Daptomycin: Spherical Micelle Formation
      Does Not Depend on the Presence of Calcium Chloride.
AB  - The cyclic lipopeptide Daptomycin, used as a treatment for infections where
      antimicrobial resistance is observed, is shown to self-assemble into spherical
      micelles above a critical aggregation concentration. Micelles are observed either
      in the absence or presence of CaCl2 , in contrast to claims in the literature
      that CaCl2 is required for micellization. 

PMID- 27043446
TI  - Hyperendemic Campylobacter jejuni in guinea pigs (Cavia porcellus) raised for
      food in a semi-rural community of Quito, Ecuador.
AB  - Domestic animals and animal products are the source of pathogenic Campylobacter
      jejuni and C. coli in industrialized countries, yet little is known about the
      transmission of these bacteria in developing countries. Guinea pigs (Cavia
      porcellus) are commonly raised for food in the Andean region of South America,
      however, limited research has characterized this rodent as a reservoir of
      zoonotic enteric pathogens. In this study, we examined the prevalence of
      Campylobacter spp. in 203 fecal samples from domestic animals of 59 households in
      a semi-rural parish of Quito, Ecuador. Of the twelve animal species studied,
      guinea pigs showed the highest prevalence of C. jejuni (n = 39/40; 97.5%).
      Multilocus sequence typing (MLST) was used to characterize the genetic
      relationship of C. jejuni from domestic animals and 21 sequence types (STs) were
      identified. The majority of STs from guinea pigs appeared to form new clonal
      complexes that were not related to STs of C. jejuni isolated from other animal
      species and shared only a few alleles with other C. jejuni previously
      characterized. The study identifies guinea pigs as a major reservoir of C. jejuni
      and suggests that some C. jejuni strains are adapted to this animal species.

PMID- 27043448
TI  - Relapse status as a prognostic factor in patients receiving salvage surgery for
      recurrent or residual nasopharyngeal cancer after definitive treatment.
AB  - BACKGROUND: The purpose of this study was to determine the prognostic value of
      relapse status (recurrent vs residual disease) in patients receiving surgical
      salvage for nasopharyngeal carcinoma (NPC). METHODS: Retrospective review was
      conducted on 52 patients who underwent salvage surgery for locoregional relapse
      of NPC. Univariate and multivariate analyses were used to investigate the
      prognostic value of relapse status. RESULTS: Median follow-up duration was 44.4
      months. Mean overall survival (OS) and disease-free survival (DFS) for patients
      with NPC with residual and recurrent disease after surgical salvage were 107.4
      and 54.4 months, and 83.6 and 34.6 months, respectively (p < .001). This improved
      survival was demonstrated regardless whether the relapse was at the primary or
      nodal site. Multivariate analysis revealed that recurrent disease status and
      nodal disease relapse were independent poor prognostic factors for survival in
      patients receiving salvage surgery for NPC. CONCLUSION: In patients undergoing
      surgical salvage for NPC relapse, residual disease carries a better prognosis
      than recurrent disease. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1393-1400,
      2016.

PMID- 27043449
TI  - In Vivo Feedback Predicts Parent Behavior Change in the Attachment and
      Biobehavioral Catch-up Intervention.
AB  - Understanding mechanisms and active ingredients of intervention is critical to
      training clinicians, particularly when interventions are transported from
      laboratories to communities. One promising active ingredient of parenting
      programs is clinicians' in vivo feedback regarding parent-child interactions. The
      present study examined whether a form of in vivo feedback, in the moment
      commenting, predicted treatment retention and parent behavior change when the
      Attachment and Biobehavioral Catch-up (ABC) intervention was implemented in a
      community setting. Observational data were collected from 78 parent-child dyads
      (96% mothers; M age = 29 years; 81% minority; infants' M age = 12 months; 90%
      minority) across 640 sessions conducted by 9 clinicians (100% female, M age = 39;
      67% minority) in Hawaii. Parental behavior was assessed with a semistructured
      play task before and after intervention. Clinicians' in-the-moment feedback to
      parents was assessed from intervention session videos. Clinicians' frequency and
      quality of in-the-moment feedback predicted change in parental intrusiveness and
      sensitivity at posttreatment. Frequency of in-the-moment feedback also predicted
      likelihood of retention. Hierarchical linear modeling demonstrated strong support
      for these associations at the between-clinician level, and limited additional
      support at the within-clinician (i.e., between-case) level. Thus, a hypothesized
      active ingredient of treatment, in-the-moment feedback, predicted community-based
      ABC outcomes. The results complement lab-based evidence to suggest that in vivo
      feedback may be a mechanism of change in parenting interventions. Helping
      clinicians to provide frequent, high-quality in vivo feedback may improve
      parenting program outcomes in community settings.

PMID- 27043451
TI  - 3D Ordered Mesoporous Bifunctional Oxygen Catalyst for Electrically Rechargeable
      Zinc-Air Batteries.
AB  - To enhance energy efficiency and durability, a highly active and durable 3D
      ordered mesoporous cobalt oxide framework has been developed for rechargeable
      zinc-air batteries. The bifunctional air electrode consisting of 3DOM Co3 O4
      having high active surface area and robust structure, results in superior charge
      and discharge battery voltages, and durable performance for electrically
      rechargeable zinc-air batteries. 

PMID- 27043450
TI  - Simultaneous Analysis of Major Coenzymes of Cellular Redox Reactions and Energy
      Using ex Vivo (1)H NMR Spectroscopy.
AB  - Coenzymes of cellular redox reactions and cellular energy mediate biochemical
      reactions fundamental to the functioning of all living cells. Despite their
      immense interest, no simple method exists to gain insights into their cellular
      concentrations in a single step. We show that a simple (1)H NMR experiment can
      simultaneously measure oxidized and reduced forms of nicotinamide adenine
      dinucleotide (NAD(+) and NADH), oxidized and reduced forms of nicotinamide
      adenine dinucleotide phosphate (NADP(+) and NADPH), and adenosine triphosphate
      (ATP) and its precursors, adenosine diphosphate (ADP) and adenosine monophosphate
      (AMP), using mouse heart, kidney, brain, liver, and skeletal muscle tissue
      extracts as examples. Combining 1D/2D NMR experiments, chemical shift libraries,
      and authentic compound data, reliable peak identities for these coenzymes have
      been established. To assess this methodology, cardiac NADH and NAD(+) ratios/pool
      sizes were measured using mouse models with a cardiac-specific knockout of the
      mitochondrial Complex I Ndufs4 gene (cKO) and cardiac-specific overexpression of
      nicotinamide phosphoribosyltransferase (cNAMPT) as examples. Sensitivity of
      NAD(+) and NADH to cKO or cNAMPT was observed, as anticipated. Time-dependent
      investigations showed that the levels of NADH and NADPH diminish by up to ~50%
      within 24 h; concomitantly, NAD(+) and NADP(+) increase proportionately; however,
      degassing the sample and flushing the sample tubes with helium gas halted such
      changes. The analysis protocol along with the annotated characteristic
      fingerprints for each coenzyme is provided for easy identification and absolute
      quantification using a single internal reference for routine use. The ability to
      visualize the ubiquitous coenzymes fundamental to cellular functions,
      simultaneously and reliably, offers a new avenue to interrogate the mechanistic
      details of cellular function in health and disease.

PMID- 27043452
TI  - MP-AzeFlu is more effective than fluticasone propionate for the treatment of
      allergic rhinitis in children.
AB  - The objective was to evaluate the efficacy of MP-AzeFlu (Dymista((r)) ) vs
      fluticasone propionate (FP), (both 1 spray/nostril bid), in children with
      allergic rhinitis (AR). MP-AzeFlu combines azelastine hydrochloride, FP and a
      novel formulation in a single spray. Children were randomized in a 3 : 1 ratio to
      MP-AzeFlu or FP in this open-label, 3-month study. Efficacy was assessed in
      children aged >= 6 to <12 years (MP-AzeFlu: n = 264; FP: n = 89), using a 4-point
      symptom severity rating scale from 0 to 3 (0 = no symptoms; 3 = severe symptoms).
      Over the 3-month period, MP-AzeFlu-treated children experienced significantly
      greater symptom relief than FP-treated children (Diff: -0.14; 95% CI: -0.28, 
      0.01; P = 0.04), noted from the first day (particularly the first 7 days) and
      sustained for 90 days. More MP-AzeFlu children achieved symptom-free or mild
      symptom severity status, and did so up to 16 days faster than FP. MP-AzeFlu
      provides significantly greater, more rapid and clinically relevant symptom relief
      than FP in children with AR.

PMID- 27043453
TI  - Preoperative serum lactate cannot predict in-hospital mortality after
      decompressive craniectomy in traumatic brain injury.
AB  - PURPOSE: Despite the utility of serum lactate for predicting clinical courses,
      little information is available on the topic after decompressive craniectomy.
      This study was conducted to determine the ability of perioperative serum lactate
      levels to predict in-hospital mortality in traumatic brain-injury patients who
      received emergency or urgent decompressive craniectomy. METHODS: The medical
      records of 586 consecutive patients who underwent emergency or urgent
      decompressive craniectomy due to traumatic brain injuries from January 2007 to
      December 2014 were retrospectively analyzed. Pre- and intraoperative serum
      lactate levels and base deficits were obtained from arterial blood gas analysis
      results. RESULTS: The overall mortality rate after decompressive craniectomy was
      26.1 %. Mean preoperative serum lactate was significantly higher in the non
      survivors (P = 0.034) than the survivors but had no significance for predicting
      in-hospital mortality in the multivariate regression analysis (P = 0.386).
      Rather, preoperative Glasgow Coma Score was a significant predictor for in
      hospital mortality (hazard ratio 0.796, 95 % confidence interval 0.755-0.836, P <
      0.001). CONCLUSION: Preoperative lactate level is not an independent predictor of
      in-hospital mortality after decompressive craniectomy in traumatic brain-injury
      patients.

PMID- 27043454
TI  - Obturator nerve injury: a rare complication of retropubic tension-free vaginal
      sling.
AB  - The tension-free vaginal tape (TVT) retropubic sling is a very effective
      treatment for stress urinary incontinence. High cure rates are typically
      achieved, and the reported complication rate is relatively low. Obturator
      neuralgia secondary to insertion of a midurethral sling is a rare and specific
      type of chronic pain that is more commonly associated with transobturator tape
      slings. The purpose of this video case report was to demonstrate that obturator
      nerve injury is a possible complication of TVT retropubic slings placement. A
      discussion of symptoms and signs of obturator nerve injury and how these should
      be managed is also presented. 

PMID- 27043455
TI  - [Not Available].

PMID- 27043456
TI  - Smoking in movies and smoking initiation in adolescents: systematic review and
      meta-analysis.
AB  - BACKGROUND AND AIMS: Preventing young people from initiating smoking is a vital
      public health objective. There is strong evidence that exposure to smoking
      imagery in movies is associated with an increased risk of smoking uptake.
      However, the estimate of the magnitude of effect is not clear, as previous
      reviews have synthesized estimates of cross-sectional and longitudinal
      associations. Therefore, we have performed a systematic review to quantify cross
      sectional and longitudinal associations between exposure to smoking in movies and
      initiating smoking in adolescents. METHODS: Four electronic databases (MEDLINE,
      EMBASE, PsycINFO and International Bibliography of the Social Sciences, IBSS) and
      grey literature were searched from inception to May 2015 for comparative
      epidemiological studies (cross-sectional and cohort studies) that reported the
      relation between exposure to smoking in movies and smoking initiation in
      adolescence (10-19 years). Reference lists of studies and previous reviews were
      also screened. Two authors screened papers and extracted data independently.
      RESULTS: Seventeen studies met our inclusion criteria. Random-effects meta
      analysis of nine cross-sectional studies demonstrated higher exposure (typically
      highest versus lowest quantile) to smoking in movies was associated significantly
      with a doubling in risk of ever trying smoking [relative risk (RR) = 1.93, 95%
      confidence interval (CI) = 1.66-2.25]. In eight longitudinal studies (all deemed
      high quality), higher exposure to smoking in movies was associated significantly
      with a 46% increased risk of initiating smoking (RR = 1.46; 95% CI = 1.23-1.73).
      These pooled estimates were significantly different from each other (P = 0.02).
      Moderate levels of heterogeneity were seen in the meta-analyses. CONCLUSIONS: The
      cross-sectional association between young people reporting having seen smoking
      imagery in films and smoking status is greater than the prospective association.
      Both associations are substantial, but it is not clear whether or not they are
      causal.

PMID- 27043457
TI  - A Prospective Study on How Symptoms in a Network Predict the Onset of Depression.

PMID- 27043458
TI  - Migration of photoinitiators from paper to fatty food simulants: experimental
      studies and model application.
AB  - The migration of five different photoinitiators from kraft paper to two fatty
      food simulants, Tenax((r)) and 95% ethanol, was investigated under different
      conditions. The effects of temperature and storage time, as well as the
      physicochemical properties of the photoinitiators on migration, were discussed.
      Mathematical models based on Fick's second law generated from two cases, single-
      and two-side contacts, were applied to predict the migration behaviour from the
      paper to the food simulants. The partition coefficients estimated from the model
      decreased with temperature. The diffusion coefficients of the selected
      photoinitiators from the paper ranged from 1.55 * 10(-10) to 7.54 * 10(-9) cm(2)
      s(-1) for Tenax and from 2.79 * 10(-9) to 8.03 * 10(-8) cm(2) s(-1) for 95%
      ethanol. The results indicate that the applied model can predict the migration of
      photoinitiators in the initial short period before equilibrium, and the migration
      from paper to Tenax through a single-side contact demonstrated an especially high
      concordance. 

PMID- 27043459
TI  - The enigmatic role of IL-22 in asthma.
AB  - Asthma is a complex, heterogeneous disorder with increasing prevalence. It is now
      recognized that several asthma phenotypes exist, including type 2-high and type 2
      low (or non-type 2) subsets. As current research strives to identify subgroups of
      asthmatics that share disease pathobiology to establish endotypes, efforts to
      clarify the underlying molecular mechanisms of disease are needed and essential.
      IL-22 is thought to be a mediator of asthma pathogenesis, but whether this
      cytokine has a pathologic or beneficial role in the lung during severe disease is
      still debated. Studies focused on the regulation of this cytokine by its
      receptors and other inflammatory mediators during allergic airway responses are
      necessary to clarify its role in disease. Here, we discuss the ambiguity
      surrounding the role of IL-22 in asthma and considerations for targeting IL-22
      therapeutically.

PMID- 27043460
TI  - Sexual Activity as a Risk Factor for the Spontaneous Rupture of Cerebral
      Aneurysms.
AB  - Subarachnoid hemorrhages from ruptured cerebral aneurysms have a high clinical
      relevance and often lead to death. Approximately 2% to 5% of the people
      worldwide, even of younger age, are said to have aneurysms at cerebral arteries.
      In many cases, they remain clinically unapparent for decades. However, there are
      numerous risk factors for the rupture of an aneurysm, including temporary raises
      of the blood pressure. Such changes of the blood pressure can be induced even by
      several everyday behaviors. For example, any sort of sexual activities may cause
      extensive raises of the blood pressure because of several physical and
      psychological factors. The term "sexual activity" covers sexual intercourse as
      well as masturbation. In this article, the remarkable case of a 24-year-old woman
      with a ruptured cerebral aneurysm in the context of masturbation is presented. It
      is discussed with respect to the possible pathophysiological effects of sexual
      activity on cerebral aneurysms. 

PMID- 27043461
TI  - Histological Changes in Skeletal Muscle During Death by Drowning: An Experimental
      Study.
AB  - A diagnosis of drowning is a challenge in legal medicine as there is generally a
      lack of pathognomonic findings indicative of drowning. This article investigates
      whether the skeletal muscle undergoes structural changes during death by
      drowning. Eighteen Wistar rats were divided into 3 equal groups according to the
      cause of death: drowning, exsanguination, and cervical dislocation. Immediately
      after death, samples of the masseter, sternohyoid, diaphragm, anterior tibial,
      soleus, and extensor digitorum longus muscles were obtained and examined by light
      and electron microscopy.In the drowning group, all muscles except the masseter
      displayed scattered evidence of fiber degeneration, and modified Gomori trichrome
      staining revealed structural changes in the form of abnormal clumps of red
      material and ragged red fibers. Under the electron microscope, there was
      myofibrillar disruption and large masses of abnormal mitochondria. In the
      exsanguination group, modified Gomori trichrome staining disclosed structural
      changes and mitochondrial abnormalities were apparent under light microscopy;
      however, there was no evidence of degeneration. No alterations were observed in
      the cervical dislocation group.As far as we know, this is the first time that
      these histological findings are described in death by drowning and are consistent
      with rhabdomyolysis and intense anoxia of skeletal muscle. 

PMID- 27043462
TI  - Immersion of Bovine Eyeballs After 1 Hour in Seawater Does Not Result in
      Elevation of Postmortem Vitreous Humor Sodium and Chloride Levels.
AB  - BACKGROUND: Elevations in postmortem vitreous sodium chloride (PMVSC) levels may
      help in differentiating saltwater/seawater drowning (SWD) deaths from immersion
      deaths not related to drowning (DNRD). It is unclear whether the elevation is
      related to blood/plasma electrolyte changes after inhalation of seawater as
      hypothesized in SWDs or possibly caused by electrolyte diffusion and/or osmosis
      across the outer coats of the eyeball during immersion. AIM: To investigate the
      changes in bovine PMVSC levels at different time points while immersed in
      seawater. METHODS: Bovine eyeballs were obtained from an abattoir and randomized
      into 2 groups: a) submerged in seawater ("wet" group) or b) placed in an
      impermeable plastic bag that was immersed in seawater ("dry" group). The PMVSC
      levels from 6 eyeballs were measured from each group (without replacement) at 30
      minutes, 1 hour, 6 hours, and 12 hours. RESULTS: There was no significant
      difference in mean PMVSC levels between the 2 groups at 30-minute and 1-hour
      intervals. A significant difference was noted from 6 hours onward. DISCUSSION:
      There is no statistically significant elevation in bovine PMVSC levels when
      immersed in seawater for up to 1 hour. Assuming similar physical properties in
      humans, any elevations in PMVSC levels in bodies immersed in seawater for less
      than 1 hour should not be caused by immersion.

PMID- 27043463
TI  - In Search of Perfect Foresight? Policy Bias, Management of Unknowns, and What Has
      Changed in Science Policy Since the Tohoku Disaster.
AB  - The failure to foresee the catastrophic earthquakes, tsunamis, and nuclear
      accident of 2011 has been perceived by many in Japan as a fundamental shortcoming
      of modern disaster risk science. Hampered by a variety of cognitive and
      institutional biases, the conventional disaster risk management planning based on
      the "known risks" led to the cascading failures of the interlinked disaster risk
      management (DRM) apparatus. This realization led to a major rethinking in the use
      of science for policy and the incorporations of lessons learned in the country's
      new DRM policy. This study reviews publicly available documents on expert
      committee discussions and scientific articles to identify what continuities and
      changes have been made in the use of scientific knowledge in Japanese risk
      management. In general, the prior influence of cognitive bias (e.g., overreliance
      on documented hazard risks) has been largely recognized, and increased attention
      is now being paid to the incorporation of less documented but known risks. This
      has led to upward adjustments in estimated damages from future risks and
      recognition of the need for further strengthening of DRM policy. At the same
      time, there remains significant continuity in the way scientific knowledge is
      perceived to provide sufficient and justifiable grounds for the development and
      implementation of DRM policy. The emphasis on "evidence-based policy" in
      earthquake and tsunami risk reduction measures continues, despite the critical
      reflections of a group of scientists who advocate for a major rethinking of the
      country's science-policy institution respecting the limitations of the current
      state science.

PMID- 27043464
TI  - Gastrointestinal: Intraductal papillary mucinous neoplasm of the pancreas:
      Radiologic-pathologic correlation.

PMID- 27043465
TI  - Pediatric whole-body MRI: A review of current imaging techniques and clinical
      applications.
AB  - There are many congenital, neoplastic, inflammatory, and infectious processes in
      the pediatric patient for which whole-body imaging may be of benefit
      diagnostically and prognostically. With recent improvements in magnetic resonance
      imaging (MRI) hardware and software and resultant dramatically reduced scan
      times, imaging of the whole body with MRI has become a much more practicable
      technique in children. Whole-body MRI can provide a high level of soft tissue and
      skeletal detail while avoiding the exposure to ionizing radiation inherent to
      computed tomography and nuclear medicine imaging techniques. This article reviews
      the more common current whole-body MRI techniques in children and the primary
      pathologies for which this imaging modality may be most useful to the
      radiologists and referring clinicians. J. MAGN. RESON. IMAGING 2016;44:783-793.

PMID- 27043466
TI  - Bulk Dissolution Rates of Cadmium and Bismuth Tellurides As a Function of pH,
      Temperature and Dissolved Oxygen.
AB  - The toxicity of Cd being well established and that of Te suspected, the bulk,
      surface-normalized steady-state dissolution rates of two industrially important
      binary tellurides-polycrystalline cadmium and bismuth tellurides- were studied
      over the pH range 3-11, at various temperatures (25-70  degrees C) and dissolved
      oxygen concentrations (0-100% O2 in the gas phase). The behavior of both
      tellurides is strikingly different. The dissolution rates of CdTe monotonically
      decreased with increasing pH, the trend becoming more pronounced with increasing
      temperature. Activation energies were of the order of magnitude associated with
      surface controlled processes; they decreased with decreasing acidity. At pH 7,
      the CdTe dissolution rate increased linearly with dissolved oxygen. In anoxic
      solution, CdTe dissolved at a finite rate. In contrast, the dissolution rate of
      Bi2Te3 passed through a minimum at pH 5.3. The activation energy had a maximum in
      the rate minimum at pH 5.3 and fell below the threshold for diffusion control at
      pH 11. No oxygen dependence was detected. Bi2Te3 dissolves much more slowly than
      CdTe; from one to more than 3.5 orders of magnitude in the Bi2Te3 rate minimum.
      Both will readily dissolve under long-term landfill deposition conditions but
      comparatively slowly.

PMID- 27043467
TI  - Uncontrolled asthma and its risk factors in Chinese children: A cross-sectional
      observational study.
AB  - OBJECTIVE: Asthma afflicts many children in China but information about asthma
      management among Chinese pediatric asthma patients is limited. This study aims to
      evaluate asthma control among Chinese pediatric patients and identify risk
      factors associated with uncontrolled asthma. METHODS: A total of 4223 patients
      with persistent asthma aged 2-16 years from 42 tertiary hospitals across all
      regions of mainland China except Tibet were surveyed. Asthma Control Test (ACT),
      Childhood Asthma Control Test (C-ACT) and Global Initiative for Asthma (GINA)
      criteria were used to assess asthma control for children aged 12-16 years, 4-11
      years and 2-3 years, respectively. Uncontrolled asthma was defined as ACT or C
      ACT score <=19 or GINA-defined uncontrolled asthma. Risk factors associated with
      uncontrolled asthma were identified using multivariate logistic regression
      models. RESULTS: Asthma was uncontrolled in 19.9% of the subjects. High rates of
      uncontrolled asthma were found in subjects with treatment non-adherence (44.1%),
      concomitant allergic rhinitis (AR) (23.3%), disease duration >= 1.5 years
      (22.8%), and first-degree relatives with AR (21.5%). The risk of uncontrolled
      asthma was much higher in the treatment non-adherence group compared to the
      complete adherence group (OR = 5.79, p < 0.001). Concomitant AR, disease duration
      >= 1.5 years, and first-degree relatives with AR were also confirmed as risk
      factors associated with uncontrolled asthma. CONCLUSIONS: About 20% of Chinese
      pediatric asthma patients had uncontrolled asthma. Treatment adherence and AR
      were the most significant risk factors. Tailored measures aimed at improving
      treatment adherence and diagnosis and treatment of AR should be adopted to
      improve the level of asthma control in Chinese children.

PMID- 27043468
TI  - Linear synthesis of the hexasaccharide related to the repeating unit of the O
      antigen from Shigella flexneri serotype 1d (I: 7,8).
AB  - Total synthesis of the hexasaccharide repeating unit of the O-antigen from
      Shigella flexneri serotype 1d (I: 7,8), alpha-D-Glcp-(1->3)-alpha-L-Rhap-(1->2)
      alpha-L-Rhap-(1->3)-alpha-L-Rhap-(1->3)-[alpha-D-Glcp-(1->4)]-beta-D-GlcpNAc, is
      reported by following a linear strategy. The target hexasaccharide was
      synthesized by sequential glycosylations of suitably protected monosaccharide
      derivatives prepared from commercially available monosaccharides through rational
      protecting group manipulations. Stereoselective glycosylations were accomplished
      by the activation of thioglycoside using N-iodosuccinimide and H2SO4-silica. The
      use of H2SO4-silica in place of traditional promoters like TfOH or TMSOTf was
      proved to be a better option for the NIS-mediated thioglycoside activation.

PMID- 27043469
TI  - Statistical model semiquantitatively approximates arabinoxylooligosaccharides'
      structural diversity.
AB  - A statistical model describing the random distribution of substituted
      xylopyranosyl residues in arabinoxylooligosaccharides is suggested and compared
      with existing experimental data. Structural diversity of
      arabinoxylooligosaccharides of various length, originating from different
      arabinoxylans (wheat flour arabinoxylan (arabinose/xylose, A/X = 0.47); grass
      arabinoxylan (A/X = 0.24); wheat straw arabinoxylan (A/X = 0.15); and
      hydrothermally pretreated wheat straw arabinoxylan (A/X = 0.05)), is
      semiquantitatively approximated using the proposed model. The suggested approach
      can be applied not only for prediction and quantification of
      arabinoxylooligosaccharides' structural diversity, but also for estimate of yield
      and selection of the optimal source of arabinoxylan for production of
      arabinoxylooligosaccharides with desired structural features.

PMID- 27043470
TI  - DFT/PCM theoretical study of the conversion of methyl 4-O-methyl-alpha-d
      galactopyranoside 6-sulfate and its 2-sulfated derivative into their 3,6-anhydro
      counterparts.
AB  - Modeling of the conversion of methyl 4-O-methyl-alpha-d-galactopyranoside 6
      sulfate (2) and 2,6-disulfate (1) into methyl 3,6-anhydro-4-O-methyl-alpha-d
      galactopyranoside (4) and its 2-sulfate (3), respectively (Scheme 1) has been
      carried out using DFT at the M06-2X/6-311 + G(d,p)//M06-2X/6-31 + G(d,p) level
      with the polarizable continuum model (PCM) in water. The three steps necessary
      for the alkaline transformation of 6-sulfated (and 2,6-disulfated) galactose
      units into 3,6-anhydro derivatives were evaluated. The final substitution step
      appears to be the rate limiting, involving an activation energy of ca. 23
      kcal/mol. The other two steps (deprotonation and chair inversion) combined
      involve lower activation energies (9-12 kcal/mol). Comparison of the
      thermodynamics and kinetics of the reactions suggest that if the deprotonation
      step precedes the chair inversion, the reaction should be faster for both
      compounds. No major differences in reaction rate can be theoretically predicted
      to be caused by the presence of sulfate on O-2, although one experimental result
      suggested that O-2 sulfation should increase the reaction rate. The
      conformational pathways are complex, given the large number of rotamers available
      for each compound, and the way that some of these rotamers combine into some of
      the pathways. In any case, the conformation (O)S2 appears as a common
      intermediate for the chair inversion processes.

PMID- 27043471
TI  - The effect of binary mixtures of zinc, copper, cadmium, and nickel on the growth
      of the freshwater diatom Navicula pelliculosa and comparison with mixture
      toxicity model predictions.
AB  - The authors investigated the effect of binary mixtures of zinc (Zn), copper (Cu),
      cadmium (Cd), and nickel (Ni) on the growth of a freshwater diatom, Navicula
      pelliculosa. A 7 * 7 full factorial experimental design (49 combinations in
      total) was used to test each binary metal mixture. A 3-d fluorescence microplate
      toxicity assay was used to test each combination. Mixture effects were predicted
      by concentration addition and independent action models based on a single-metal
      concentration-response relationship between the relative growth rate and the
      calculated free metal ion activity. Although the concentration addition model
      predicted the observed mixture toxicity significantly better than the independent
      action model for the Zn-Cu mixture, the independent action model predicted the
      observed mixture toxicity significantly better than the concentration addition
      model for the Cd-Zn, Cd-Ni, and Cd-Cu mixtures. For the Zn-Ni and Cu-Ni mixtures,
      it was unclear which of the 2 models was better. Statistical analysis concerning
      antagonistic/synergistic interactions showed that the concentration addition
      model is generally conservative (with the Zn-Ni mixture being the sole
      exception), indicating that the concentration addition model would be useful as a
      method for a conservative first-tier screening-level risk analysis of metal
      mixtures. Environ Toxicol Chem 2016;35:2765-2773. (c) 2016 SETAC.

PMID- 27043472
TI  - Wound healing activity of the ethanol root extract and polyphenolic rich fraction
      from Potentilla fulgens.
AB  - CONTEXT: Potentilla fulgens Wall. ex Hook (Rosaceae) is a potent medicinal plant
      of the Western Himalayas, where its roots are traditionally used by the local
      people of Uttaranchal (India) to treat wounds and tiger bites. OBJECTIVE: The
      present study scientifically evaluates the wound healing activity of P. fulgens
      ethanol root extract (EPF) and its ethyl acetate fraction (PFEA) on experimental
      rats. MATERIALS AND METHODS: Wounds were inflicted on animals by using both
      excision and incision models. The wounded animals were treated for 16 days with
      EPF (oral: 200-400 mg/kg and topical: 5-10% w/w) and PFEA (oral: 75 mg/kg;
      topical: 1.75% w/w). Various physical (wound contraction, epithelialization rate,
      tensile strength) and biochemical parameters (hydroxyproline, hexosamine,
      proteins, DNA) were examined during the study. Oxidant product (lipidperoxidase),
      antioxidant enzymes (catalase, superoxide-dismutase) and reduced glutathione were
      determined. Morphological and histopathological studies of the skin tissues were
      monitored. RESULTS: A significant (p < 0.05) wound healing property was observed
      when the animals were treated topically with EPF (10% w/w) and PFEA (1.75% w/w).
      A significantly (p < 0.05) increased in the levels of hydroxyproline, hexosamine,
      protein and DNA up to 59.22, 70.42, 61.01 and 60.00% was observed, respectively.
      This effect was further demonstrated by the morphological and histopathological
      representation, thus showing significant (p < 0.05) re-epethelialization on the
      healing area. EPF and PFEA also showed significant (p < 0.05) antioxidant
      activity. CONCLUSIONS: The present study provided the scientific evidence, where
      P. fulgens rich in polyphenolic components possess remarkable wound healing
      activities, thereby supporting the traditional claims.

PMID- 27043473
TI  - Properties of nitrogen fertilization are decisive in determining the effects of
      elevated atmospheric CO2 on the activity of nitrate reductase in plants.
AB  - The concentration of atmospheric CO2 is predicted to double by the end of this
      century. The response of higher plants to an increase in atmospheric CO2 often
      includes a change in nitrate reductase (NR) activity. In a recent study, we
      showed that, under elevated CO2 levels, NR induction in low-nitrate plants and NR
      inhibition in high-nitrate plants are regulated by nitric oxide (NO) generated
      via nitric oxide synthases. This finding provides an explanation for the diverse
      responses of plants to elevated CO2 levels, and suggests that the use of nitrogen
      fertilizers on soil will have a major influence on the nitrogen assimilation
      capacity of plants in response to CO2 elevation. 

PMID- 27043474
TI  - How Do We Remember Happy Life Events? A Comparison Between Eudaimonic and Hedonic
      Autobiographical Memories.
AB  - Although positive events occur frequently in people's lives, autobiographical
      memory for happy events has received only marginal attention within the
      psychology literature. This study followed a between-subjects design to examine
      the similarities and differences between eudaimonic and hedonic happy memories.
      Two groups of undergraduates provided narratives of personally experienced
      eudaimonic and hedonic events, respectively. They also completed questionnaires
      assessing the memory characteristics of recalled events and the centrality of
      such events for the individual's identity and life story. In addition, the
      participants' levels of well-being were assessed. The content analysis of
      narratives revealed that eudaimonic memories mostly referred to transitional life
      events; by contrast, the most reported hedonic memories referred to close
      relationship experiences. Eudaimonic and hedonic recollections were further
      compared on quantitative measures of memory characteristics, statistically
      controlling for retention interval and event centrality. Results showed that
      eudaimonic memories involved more intense feelings of pride and were socially
      shared more frequently than hedonic memories. However, the two memory types were
      similar with respect to a number of features (e.g., sensory details). It is
      argued that participants remembering eudaimonic events were more influenced by
      cultural life scripts. Implications of the findings for the measurement of
      psychological well-being are also discussed. 

PMID- 27043475
TI  - Evaluating the impact of missenses mutations in CYP2D6*7 and CYP2D6*14A: does it
      compromise tamoxifen metabolism?
AB  - CYP2D6 is a high polymorphic enzyme from P450, responsible for metabolizing
      almost 25% of drugs. The distribution of different mutations among CYP2D6 alleles
      has been associated with poor, intermediate, extensive and ultra-metabolizers.
      AIM: To evaluate how missenses mutations in CYP2D6*7 and CYP2D6*14A poor
      metabolizer alleles affect CYP2D6 stability and function. MATERIALS & METHODS:
      CYPalleles database was used to collect polymorphisms data present in 105
      alleles. We selected only poor metabolizers alleles that presented exclusively
      missenses mutations. They were analyzed through seven algorithms to predict the
      impact on CYP2D6 structure and function. RESULTS: H324P, the unique mutation in
      CYP2D6*7, has high impact in enzyme function due to its occurrence between two
      alpha-helixes involved in active site dynamics. G169R, a mutation that occurs
      only in CYP2D6*14A, leads to the gain of solvent accessibility and severe protein
      destabilization. CONCLUSION: Our in silico analysis showed that missenses
      mutations in CYP2D6*7 and CYP2D6*14A cause CYP2D6 dysfunction.

PMID- 27043476
TI  - DNA damage by the sulfate radical anion: hydrogen abstraction from the sugar
      moiety versus one-electron oxidation of guanine.
AB  - The products of oxidative damage to double-stranded (ds) DNA initiated by
      photolytically generated sulfate radical anions SO4(*-) were analyzed using
      reverse-phase (RP) high-performance liquid chromatography (HPLC). Relative
      efficiencies of two major pathways were compared: production of 8-oxoguanine
      (8oxoG) and hydrogen abstraction from the DNA 2-deoxyribose moiety (dR) at C1,'
      C4,' and C5' positions. The formation of 8oxoG was found to account for 87% of
      all quantified lesions at low illumination doses. The concentration of 8oxoG
      quickly reaches a steady state at about one 8oxoG per 100 base pairs due to
      further oxidation of its products. It was found that another guanine oxidation
      product identified as 2-amino-5-(2'-alkylamino)-4H-imidazol-4-one (X) was
      released in significant quantities from its tentative precursor 2-amino-5-[(2'
      deoxy-beta-d-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (dIz) upon treatment
      with primary amines in neutral solutions. The linear dose dependence of X release
      points to the formation of dIz directly from guanine and not through oxidation of
      8oxoG. The damage to dR was found to account for about 13% of the total damage,
      with majority of lesions (33%) originating from the C4' oxidation. The
      contribution of C1' oxidation also turned out to be significant (17% of all dR
      damages) despite of the steric problems associated with the abstraction of the
      C1'-hydrogen. However, no evidence of base-to-sugar free valence transfer as a
      possible alternative to direct hydrogen abstraction at C1' was found. 

PMID- 27043477
TI  - Health Versus Appearance Versus Body Competence: A Content Analysis Investigating
      Frames of Health Advice in Women's Health Magazines.
AB  - The present study investigated the extent to which women's health magazines
      advise readers to adopt healthy behaviors in order to look good (appearance
      frame), in order to feel good (health frame), or in order to perform better (body
      competence frame). A content analysis of 5 years of the 6 highest circulating
      U.S. women's health magazines revealed a higher frequency of health frames
      (32.6%) than appearance frames (24.8%) overall, but when beauty/health hybrid
      magazines (i.e., Shape and Self) were examined separately, appearance frames
      (32.8%) outnumbered health frames (26.5%). Compared to appearance and health
      frames, body competence frames were underrepresented (13.3% in the full sample).
      The visual sexual objectification of female models in women's health magazines
      was also investigated. Appearance-framed articles (43.2%) were significantly more
      likely to visually depict women with a high degree of skin exposure than health
      framed articles (17.4%), and appearance-framed articles (34.8%) were more likely
      to focus on individual body parts than health-framed articles (21.3%). In
      addition, despite the magazines' editorial focus on health, the most frequent
      category of products advertised was appearance-enhancing products. Results are
      discussed in light of self-determination theory (Deci & Ryan, 1985) and
      objectification theory (Fredrickson & Roberts, 1997).

PMID- 27043478
TI  - Rapid electrical immunoassay of the cardiac biomarker troponin I through
      dielectrophoretic concentration using imbedded electrodes.
AB  - Rapidity and high sensitivity are critical factors for the diagnoses of heart
      attacks, and cardiac troponin I (cTnI) is at present a clinical standard for its
      diagnosis. Here we report a rapid, label-free, and highly sensitive single-walled
      carbon nanotube (SWCNT) electrical immunosensor, featuring two pairs of
      electrodes. Two concentration electrodes (gaps: 25 and 80um) and two detection
      electrodes (source and drain; gap: 20um; width: 50um) were used for
      dielectrophoretic concentration of cTnI on the SWCNT channels and resistance
      measurements of the dielectrophoresis (DEP)-concentrated cTnI, respectively. The
      two concentration electrodes were imbedded between upper and lower dielectric
      layers, facing each other, underneath the -COOH-functionalized SWCNT channels
      deposited between the detection electrodes. Therefore, the gap between these
      imbedded concentration electrodes can be reduced to maximize the electric field
      intensity for DEP-mediated concentration of cTnI, thereby greatly reducing the
      detection time (1min) and enhancing the limit of detection (0.7-0.8pgmL(-)(1)).
      Relative resistance changes of the SWCNTs were measured as cTnI concentration in
      Tris-Borate-EDTA (TBE; 0.0025*) and human serum diluted 500-fold with 0.0025* TBE
      decreased from 100ngmL(-)(1) to 1pgmL(-1), and they were shown to be linear with
      the logarithm of cTnI concentration (R(2)=0.99 and 0.97, respectively). These
      immunosensors also showed high specificity over another cardiac biomarker,
      myoglobin, TBE medium (0.0025*), and 500-fold diluted human serum. The DEP
      capture of cTnI depended on the frequency of the applied electric field,
      demonstrating the qualitative nature of the real part of the Clausius-Mossotti
      factor for cTnI. 

PMID- 27043479
TI  - A reversible and highly selective fluorescence "on-off-on" probe for detecting
      nickel ion in the mitochondria of living cells.
AB  - A simple molecular fluorescent probe L has been designed, synthesized and
      characterized. The probe upon interaction with different metals ions show high
      selectivity and sensitivity for Ni(2+) through fluorescence "turn-off" response
      in acetonitrile, and the fluorescence could be recovered when chelating agent
      TPEN is added in this system, viz an "on-off-on" process. Its recognition
      mechanism has been established by fluorescence spectra, (1)H NMR study. Moreover,
      to further explore its utility in biological system, L is selected as a probe for
      Ni(2+) indicator in live cells and shows sensitivity on Ni(2+) intracellular
      distribution. Fluorescence co-localization studies demonstrate that L is a
      specific mitochondria-targeted fluorescent probe with excellent cell membrane
      permeability. Furthermore, a rapidly reversible fluorescence imaging of probe L
      detecting Ni(2+) in the mitochondria is successfully achieved. These facts would
      make this probe a great potential for detecting Ni(2+) in biology. 

PMID- 27043480
TI  - Evaluation of hyperdense renal lesions incidentally detected on single-phase post
      contrast CT using dual-energy CT.
AB  - OBJECTIVE: To investigate the utility of dual-energy CT (DECT) for
      differentiating between solid and benign cystic lesions presenting as hyperdense
      renal lesions incidentally detected on single-phase post-contrast CT. METHODS: 90
      hyperdense renal lesions incidentally detected on single-phase post-contrast CT
      were evaluated with follow-up DECT. DECT protocols included true non-contrast
      (TNC), DE corticomedullary and DE late nephrographic phase imaging. The CT
      numbers of hyperdense renal lesions were calculated on linearly blended and
      iodine overlay (IO) images, and the results were compared. RESULTS: In total, 47
      benign cystic and 43 solid renal lesions were analyzed. For differentiating
      between solid and benign cystic lesions on the two phases, the specificity and
      accuracy of all lesions and lesions <1.5 cm were statistically lower in IO images
      than in linearly blended images (p < 0.05), while those for lesions >=1.5 cm were
      not statistically different between them (p > 0.05). For all types of lesions
      >=1.5 cm, the CT numbers between linearly blended and IO images and between TNC
      and virtual non-contrast images were not statistically different (p > 0.05).
      CONCLUSION: DECT may be useful for differentiating between solid and benign
      cystic lesions presenting as hyperdense renal lesions incidentally detected on
      single-phase post-contrast CT, particularly with the size >=1.5 cm. ADVANCES IN
      KNOWLEDGE: DECT may be used to characterize hyperdense renal lesions >=1.5 cm
      incidentally detected on single-phase post-contrast CT, without the use of TNC
      images.

PMID- 27043481
TI  - Crop responses to elevated CO2 and interactions with H2O, N, and temperature.
AB  - About twenty-seven years ago, free-air CO2 enrichment (FACE) technology was
      developed that enabled the air above open-field plots to be enriched with CO2 for
      entire growing seasons. Since then, FACE experiments have been conducted on
      cotton, wheat, ryegrass, clover, potato, grape, rice, barley, sugar beet,
      soybean, cassava, rape, mustard, coffee (C3 crops), and sorghum and maize (C4
      crops). Elevated CO2 (550ppm from an ambient concentration of about 353ppm in
      1990) decreased evapotranspiration about 10% on average and increased canopy
      temperatures about 0.7 degrees C. Biomass and yield were increased by FACE in all
      C3 species, but not in C4 species except when water was limiting. Yields of C3
      grain crops were increased on average about 19%.

PMID- 27043482
TI  - A diarylpentanoid curcumin analog exhibits improved radioprotective potential in
      the intestinal mucosa.
AB  - PURPOSE: To best enhance the effects of radiotherapy, it is important to minimize
      adverse events, including free radical-induced intestinal cell damage. Given the
      threat of nuclear power plant accidents or nuclear terrorism, there is an urgent
      need for radioprotectants to counteract the radiation-induced toxicity and/or
      injuries. Curcumin exhibits protective effects against gamma irradiation;
      however, its in vivo efficacy is decreased due to the low bioavailability. We
      examined the radioprotective effect of a newly synthesized curcumin analog, GO
      Y031, on 11-Gy X-ray-induced intestinal mucosal damage in mice. MATERIALS AND
      METHODS: The radioprotection experiments were conducted by using C57BL/6J or
      Jcl:ICR mice. Molecules related to radiation damage, including p53, Bax, Bcl-2,
      cleaved caspase-3, and reactive carbonyl species (RCS), were investigated
      immunohistochemically. RESULTS: GO-Y031 protected against crypt hypoplasia
      relative to a mock treatment at 0.5% (weight/weight); the number of crypts were
      11.00 +/- 2.00/circumference (mm) in treated versus 6.86 +/- 0.99/mm in mock
      treated C57BL/6 mice (p = 0.0079). GO-Y031 also reduced the levels of RCS, p53,
      and cleaved caspase-3 accumulation in the irradiated intestinal cells.
      CONCLUSIONS: GO-Y031 suppresses the accumulation of RCS and apoptosis-related
      molecules in irradiated cells. This compound may be a good primary
      radioprotective compound.

PMID- 27043483
TI  - Determinants of Paracentrotus lividus sea urchin recruitment under oligotrophic
      conditions: Implications for conservation management.
AB  - Sea urchins may deeply shape the structure of macrophyte-dominated communities
      and require the implementation of sustainable management strategies. In the
      Mediterranean, the identification of the major recruitment determinants of the
      keystone sea urchin species Paracentrotus lividus is required, so that source
      areas of the populations can be identified and exploitation or programmed
      harvesting can be spatially managed. In this study a collection of eight possible
      determinants, these encompassing both the biotic (larvae, adult sea urchins,
      fish, encrusting coralline algae, habitat type and spatial arrangement of
      habitats) and abiotic (substrate complexity and nutritional status) realms was
      considered at different spatial scales (site, area, transect and quadrat). Data
      from a survey including sites subject to different levels of human influence
      (i.e. from urbanized to protected areas), but all corresponding to an
      oligotrophic and low-populated region were fitted by means of a generalized
      linear mixed model. Despite the extensive sampling effort of benthic quadrats, an
      overall paucity of recruits was found, recruits being aggregated in a very small
      number of quadrats and in few areas. The analysis of data detected substrate
      complexity, and adult sea urchin and predatory fish abundances as the momentous
      determinants of Paracentrotus lividus recruitment. Possible mechanisms of
      influence are discussed beyond the implications of conservation management. 

PMID- 27043484
TI  - Circumcision is a primary preventive against HIV infection: Critique of a
      contrary meta-regression analysis by Van Howe.
AB  - A meta-analysis by Van Howe of 109 populations confirms the well-known
      association of male circumcision (MC) with reduced HIV prevalence. He then
      performed meta-regression adjusting for location, risk and MC prevalence. When
      one or two of these adjustments in combination were applied MC appeared
      protective, but when all three were introduced the association remained
      significant in high-risk populations, but not in general populations within
      Africa with a hypothetical MC prevalence of <25% or elsewhere with hypothetical
      MC prevalence of <75%. However, many MC prevalence values given differed from
      those reported in references cited (including all US studies). This and other
      problems invalidate his adjustments for MC prevalence, undermining most of his
      meta-regression results. Meta-regression is a highly sophisticated statistical
      tool and is prone to error if not applied correctly. The study contained a high
      risk of bias arising from confounding. We also question his use of crude, rather
      than adjusted, odds ratios and his inclusion of unpublished data, so precluding
      replication by others. Flawed statistics, opaque presentation of results and
      inclusion of previously repudiated arguments downplaying a role for MC in HIV
      prevention programmes should lead readers to be sceptical of the findings and
      conclusions of Van Howe's study.

PMID- 27043485
TI  - Association study for the role of Matrix metalloproteinases 2 and 3 gene
      polymorphisms in dental caries susceptibility.
AB  - OBJECTIVE: Various exogenous and endogenous risk factors have been described as
      contributing to dental caries susceptibility. In the last decade it has been
      established that both pro and active forms of host derived Matrix
      metalloproteinases (MMPs) are present in the oral cavity. MMPs role in caries
      development has been hypothesized. The aim of this study was to analyse MMP2
      (rs2287074) and MMP3 (rs679620) single nucleotide polymorphisms (SNPs) and their
      role in caries susceptibility. DESIGN: The two SNPs were analysed by PCR-
      restriction fragment length polymorphism (RFLP) in a sample of 102 ethnic
      Bulgarian volunteers (42 males and 60 females), all students in Sofia Medical
      University. RESULTS: Statistical analysis of the MMP2 SNP showed significant
      differences for the genotype frequencies between the caries free (CF, DMFT=0) and
      low caries experience (LCE, DMFT<=5) groups. Analysis for the non-synonymous MMP3
      SNP found significant differences between both CF vs caries experience groups
      (LCE+ high caries experience (HCE, DMFT>=5)) and LCE vs HCE groups. The presence
      of allele G decreased the risk of HCE about 4 times. CONCLUSIONS: MMP2 and MMP3
      genes are likely to be involved in caries susceptibility in our population.
      However, as dental caries is a multifactorial disorder and several genes are
      likely to have influence on it, it is reasonable to expect that SNPs, even those
      proven to be functional like rs679620, potentially play a significant, but not
      major role in the disease outcome.

PMID- 27043487
TI  - Biochemical characterization of vitreous amyloid formed after liver
      transplantation.

PMID- 27043488
TI  - Novartis Reply to the ATMOSPHERE Data Monitoring Committee.

PMID- 27043489
TI  - Current evidence supporting mucosal healing and deep remission as important
      treatment goals for inflammatory bowel disease.
AB  - Mucosal healing (MH) is now considered as a major treatment goal in clinical
      trials and clinical practice for patients with inflammatory bowel disease (IBD).
      MH is associated with sustained clinical remission, steroid-free remission, and
      reduced rates of hospitalization and surgery. There is a well-known disconnect
      between clinical symptoms and mucosal lesions that is more pronounced in CD. More
      stringent therapeutic goals have been discussed recently such as deep remission
      defined as clinical remission associated with MH. Recent international guidelines
      from the IOIBD recommended deep remission as a treatment goal in clinical
      practice. However there is no validated definition of deep remission in IBD.
      Also, the efficacy of available drugs to induce and maintain deep remission in
      IBD is poorly known. Finally, whether deep remission is the best way to modify
      the course of IBD and whether it should be achieved before considering drug de
      escalation have to be formally evaluated in upcoming disease-modification trials.

PMID- 27043490
TI  - Lifespan Weighed Down by Diet.

PMID- 27043491
TI  - Reply to: does deep neuromuscular blockade affect pain after laparoscopic
      surgery?

PMID- 27043492
TI  - Does deep neuromuscular block affect pain after laparoscopic surgery?

PMID- 27043496
TI  - Preliminary LC-MS Based Screening for Inhibitors of Plasmodium falciparum
      Thioredoxin Reductase (PfTrxR) among a Set of Antimalarials from the Malaria Box.
AB  - Plasmodium falciparum thioredoxin reductase (PfTrxR) has been identified as a
      potential drug target to combat growing antimalarial drug resistance. Medicines
      for Malaria Venture (MMV) has pre-screened and identified a set of 400
      antimalarial compounds called the Malaria Box. From those, we have evaluated
      their mechanisms of action through inhibition of PfTrxR and found new active
      chemical scaffolds. Five compounds with significant PfTrxR inhibitory activity,
      with IC50 values ranging from 0.9-7.5 uM against the target enzyme, were found
      out of the Malaria Box. 

PMID- 27043493
TI  - Intravascular volume therapy in adults: Guidelines from the Association of the
      Scientific Medical Societies in Germany.

PMID- 27043495
TI  - Inflammatory signaling in human tuberculosis granulomas is spatially organized.
AB  - Granulomas are the pathological hallmark of tuberculosis (TB). However, their
      function and mechanisms of formation remain poorly understood. To understand the
      role of granulomas in TB, we analyzed the proteomes of granulomas from subjects
      with tuberculosis in an unbiased manner. Using laser-capture microdissection,
      mass spectrometry and confocal microscopy, we generated detailed molecular maps
      of human granulomas. We found that the centers of granulomas have a pro
      inflammatory environment that is characterized by the presence of antimicrobial
      peptides, reactive oxygen species and pro-inflammatory eicosanoids. Conversely,
      the tissue surrounding the caseum has a comparatively anti-inflammatory
      signature. These findings are consistent across a set of six human subjects and
      in rabbits. Although the balance between systemic pro- and anti-inflammatory
      signals is crucial to TB disease outcome, here we find that these signals are
      physically segregated within each granuloma. From the protein and lipid snapshots
      of human and rabbit lesions analyzed here, we hypothesize that the pathologic
      response to TB is shaped by the precise anatomical localization of these
      inflammatory pathways during the development of the granuloma.

PMID- 27043494
TI  - Epithelial calcineurin controls microbiota-dependent intestinal tumor
      development.
AB  - Inflammation-associated pathways are active in intestinal epithelial cells (IECs)
      and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a
      phosphatase required for the activation of the nuclear factor of activated T
      cells (NFAT) family of transcription factors, shows increased expression in CRC.
      We therefore investigated the role of calcineurin in intestinal tumor
      development. We demonstrate that calcineurin and NFAT factors are constitutively
      expressed by primary IECs and selectively activated in intestinal tumors as a
      result of impaired stratification of the tumor-associated microbiota and toll
      like receptor signaling. Epithelial calcineurin supports the survival and
      proliferation of cancer stem cells in an NFAT-dependent manner and promotes the
      development of intestinal tumors in mice. Moreover, somatic mutations that have
      been identified in human CRC are associated with constitutive activation of
      calcineurin, whereas nuclear translocation of NFAT is associated with increased
      death from CRC. These findings highlight an epithelial cell-intrinsic pathway
      that integrates signals derived from the commensal microbiota to promote
      intestinal tumor development.

PMID- 27043497
TI  - Antioxidant and Anti-Inflammatory Effects of Chaenomeles sinensis Leaf Extracts
      on LPS-Stimulated RAW 264.7 Cells.
AB  - The fruit of Chaenomeles sinensis has been traditionally used in ethnomedicine
      for the treatment of various human ailments, including pneumonia, bronchitis, and
      so on, but the pharmacological applications of the leaf part of the plant have
      not been studied. In this study, we evaluated the various radical scavenging
      activities and anti-inflammatory effects of different Chaenomeles sinensis leaf
      (CSL) extracts. The water extract showed a higher antioxidant and radical
      scavenging activities. However the ethanolic extracts showed higher NO scavenging
      activity than water extract, therefore the ethanolic extract of CSL was examined
      for anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW 264.7
      cells. The 70% ethanol extract of CSL (CSLE) has higher anti-inflammatory
      activity and significantly inhibited the production of nitric oxide (NO),
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). In addition,
      CSLE suppressed LPS-stimulated inducible nitric oxide synthase (iNOS) and NO
      production, IL-1beta and phospho-STAT1 expression. In this study, we investigated
      the effect of CSLE on the production of inflammatory mediators through the
      inhibition of the TRIF-dependent pathways. Furthermore, we evaluated the role of
      CSLE on LPS-induced expression of pro-inflammatory cytokines, such as TNF-alpha,
      IL-1beta and IL-6. Our results suggest that CSLE attenuates the LPS-stimulated
      inflammatory responses in macrophages through regulating the key inflammatory
      mechanisms, providing scientific support for its traditional uses in treating
      various inflammatory diseases. 

PMID- 27043498
TI  - Methods for Improving Aptamer Binding Affinity.
AB  - Aptamers are single stranded oligonucleotides that bind a wide range of
      biological targets. Although aptamers can be isolated from pools of random
      sequence oligonucleotides using affinity-based selection, aptamers with high
      affinities are not always obtained. Therefore, further refinement of aptamers is
      required to achieve desired binding affinities. The optimization of primary
      sequences and stabilization of aptamer conformations are the main approaches to
      refining the binding properties of aptamers. In particular, sequence optimization
      using combined in silico sequence recombinations and in vitro functional
      evaluations is effective for the improvement of binding affinities, however, the
      binding affinities of aptamers are limited by the low hydrophobicity of nucleic
      acids. Accordingly, introduction of hydrophobic moieties into aptamers expands
      the diversity of interactions between aptamers and targets. Moreover,
      construction of multivalent aptamers by connecting aptamers that recognize
      distinct epitopes is an attractive approach to substantial increases in binding
      affinity. In addition, binding affinities can be tuned by optimizing the
      scaffolds of multivalent constructs. In this review, we summarize the various
      techniques for improving the binding affinities of aptamers. 

PMID- 27043499
TI  - Conformational and Molecular Structures of alpha,beta-Unsaturated Acrylonitrile
      Derivatives: Photophysical Properties and Their Frontier Orbitals.
AB  - We report single crystal X-ray diffraction (hereafter, SCXRD) analyses of
      derivatives featuring the electron-donor N-ethylcarbazole or the (4
      diphenylamino)phenyl moieties associated with a -CN group attached to a double
      bond. The compounds are (2Z)-3-(4-(diphenylamino)-phenyl)-2-(pyridin-3-yl)prop-2
      enenitrile (I), (2Z)-3-(4-(diphenylamino)phenyl)-2-(pyridin-4-yl)-prop-2
      enenitrile (II) and (2Z)-3-(9-ethyl-9H-carbazol-3-yl)-2-(pyridin-2-yl)enenitrile
      (III). SCXRD analyses reveal that I and III crystallize in the monoclinic space
      groups P2/c with Z' = 2 and C2/c with Z' = 1, respectively. Compound II
      crystallized in the orthorhombic space group Pbcn with Z' = 1. The molecular
      packing analysis was conducted to examine the pyridine core effect, depending on
      the ortho, meta- and para-positions of the nitrogen atom, with respect to the
      optical properties and number of independent molecules (Z'). It is found that the
      double bond bearing a diphenylamino moiety introduced properties to exhibit a
      strong pi-pi-interaction in the solid state. The compounds were examined to
      evaluate the effects of solvent polarity, the role of the molecular structure,
      and the molecular interactions on their self-assembly behaviors. Compound I
      crystallized with a cell with two conformers, anti and syn, due to interaction
      with solvent. DFT calculations indicated the anti and syn structures of I are
      energetically stable (less than 1 eV). Also electrochemical and photophysical
      properties of the compounds were investigated, as well as the determination of
      optimization calculations in gas and different solvent (chloroform, cyclohexane,
      methanol, ethanol, tetrahydrofuran, dichloromethane and dimethyl sulfoxide) in
      the Gaussian09 program. The effect of solvent by PCM method was also
      investigated. The frontier HOMO and LUMO energies and gap energies are reported. 

PMID- 27043500
TI  - NMR Study on the Inclusion Complexes of beta-Cyclodextrin with Isoflavones.
AB  - The structure of the inclusion complexes of beta-cyclodextrin (beta-CD) with
      daidzein and daidzin in D2O were investigated using NMR spectroscopy. For the
      beta-CD and daidzein system, two types of 1:1 complexes were formed with the
      daidzein deeply inserted into the CD cavity with different orientations. For the
      beta-CD/daidzin system, a 1:1 complex was formed with the flavonoid part of
      daidzin entering the CD cavity from the wide rim. The inclusion complexes
      determined by NMR were constructed using molecular docking. Furthermore, the
      mixture of puerarin, daidzein and daidzin, which are the major isoflavonoid
      components present in Radix puerariae, was analyzed by diffusion-ordered
      spectroscopy (DOSY) alone and upon addition of beta-CD in order to mimic
      chromatographic conditions and compare their binding affinities.

PMID- 27043501
TI  - The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity.
AB  - Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during
      the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first
      became available for clinical consumption in 1962 and was used mainly for urinary
      tract infections caused by Escherichia coli and other pathogenic Gram-negative
      bacteria. Recently, significant work has been carried out to synthesize novel
      quinolone analogues with enhanced activity and potential usage for the treatment
      of different bacterial diseases. These novel analogues are made by substitution
      at different sites--the variation at the C-6 and C-8 positions gives more
      effective drugs. Substitution of a fluorine atom at the C-6 position produces
      fluroquinolones, which account for a large proportion of the quinolones in
      clinical use. Among others, substitution of piperazine or methylpiperazine,
      pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of
      twenty six analogues are reported in this review. The targets of quinolones are
      two bacterial enzymes of the class II topoisomerase family, namely gyrase and
      topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA
      cleavage complexes and convert them into cellular toxins; as a result they are
      bactericidal. High bioavailability, relative low toxicity and favorable
      pharmacokinetics have resulted in the clinical success of fluoroquinolones and
      quinolones. Due to these superior properties, quinolones have been extensively
      utilized and this increased usage has resulted in some quinolone-resistant
      bacterial strains. Bacteria become resistant to quinolones by three mechanisms:
      (1) mutation in the target site (gyrase and/or topoisomerase IV) of quinolones;
      (2) plasmid-mediated resistance; and (3) chromosome-mediated quinolone
      resistance. In plasmid-mediated resistance, the efflux of quinolones is increased
      along with a decrease in the interaction of the drug with gyrase (topoisomerase
      IV). In the case of chromosome-mediated quinolone resistance, there is a decrease
      in the influx of the drug into the cell.

PMID- 27043502
TI  - Insolubilization of Chestnut Shell Pigment for Cu(II) Adsorption from Water.
AB  - Chestnut shell pigment (CSP) is melanin from an agricultural waste. It has
      potential as an adsorbent for wastewater treatment but cannot be used in its
      original state because of its solubility in water. We developed a new method to
      convert CSP to insolubilized chestnut shell pigment (ICSP) by heating, and the
      Cu(II) adsorption performance of ICSP was evaluated. The conversion was
      characterized, and the thermal treatment caused dehydration and loss of carboxyl
      groups and aliphatic structures in CSP. The kinetic adsorption behavior obeyed
      the pseudo-second-order rate law, and the equilibrium adsorption data were well
      described with both the Langmuir and the Freundlich isotherms. ICSP can be used
      as a renewable, readily-available, easily-producible, environmentally-friendly,
      inexpensive and effective adsorbent to remove heavy-metal from aquatic
      environments. 

PMID- 27043503
TI  - GC*GC-TOFMS Analysis of Essential Oils Composition from Leaves, Twigs and Seeds
      of Cinnamomum camphora L. Presl and Their Insecticidal and Repellent Activities.
AB  - Interest in essential oils with pesticidal activity against insects and pests is
      growing. In this study, essential oils from different parts (leaves, twigs and
      seeds) of Cinnamomum camphora L. Presl were investigated for their chemical
      composition, and insecticidal and repellent activities against the cotton aphid.
      The essential oils, obtained by hydrodistillation, were analyzed by GC*GC-TOFMS.
      A total of 96 components were identified in the essential oils and the main
      constituents found in the leaves and twigs were camphor, eucalyptol, linalool and
      3,7-dimethyl-1,3,7-octatriene. The major components found in the seeds were
      eucalyptol (20.90%), methyleugenol (19.98%), linalool (14.66%) and camphor
      (5.5%). In the contact toxicity assay, the three essential oils of leaves, twigs
      and seeds exhibited a strong insecticidal activity against cotton aphids with
      LC50 values of 245.79, 274.99 and 146.78 mg/L (after 48 h of treatment),
      respectively. In the repellent assay, the highest repellent rate (89.86%) was
      found in the seed essential oil at the concentration of 20 MUL/mL after 24 h of
      treatment. Linalool was found to be a significant contributor to the insecticidal
      and repellent activities. The results indicate that the essential oils of C.
      camphora might have the potential to be developed into a natural insecticide or
      repellent for controlling cotton aphids. 

PMID- 27043504
TI  - Bryonolic Acid, a Triterpenoid, Protect Against N-methyl-d-Aspartate-Induced
      Neurotoxicity in PC12 Cells.
AB  - Calcium overload is considered to be one of the mechanisms of cerebral ischemia.
      Ca(2+) influx and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and cAMP
      response element-binding protein (CREB) phosphorylation are considered to be
      involved in N-Methyl-d-aspartate (NMDA)-induced apoptosis process. This study
      investigated the neuroprotective effects of bryonolic acid (BA) in an NMDA
      induced rat adrenal pheochromocytoma cell line (PC12) cells and the potential
      mechanism. PC12 was treated by NMDA to establish an excitotoxicity model. BA
      (110,100 and 1000 MUM final concentration) was added to the medium 24 h prior to
      the addition of NMDA. Subsequently, a methyl thiazolyl tetrazolium (MTT) assay
      and a lactate dehydrogenase (LDH) release were performed. Ca(2+) concentration
      was demonstrated using a scanning-dual wavelength fluorimetric method. In
      addition, protein and mRNA levels were determined via Western blot and real-time
      PCR. In the presence of BA, MTT assay and LDH assay showed that more cells were
      viable in comparison with the NMDA group. Moreover, the concentration of Ca(2+)
      decreased with the addition of BA in culture. Furthermore, BA could upregulate
      protein expressions of Bcl-2, p-CREB, and p-CaMKII and downregulate protein
      expression of Bax. The mRNA results showed that the pattern of mRNA expression
      were similar to their respective protein levels. All these results indicate that
      BA protected PC12 cells against NMDA-induced apoptosis by inhibiting Ca(2+)
      influx and regulating gene expression in the Ca(2+)-CaMKII-CREB signal pathway.
      Therefore, the present study supports the notion that BA may be a promising
      neuroprotective agent for the treatment of cerebral ischemia disease. 

PMID- 27043505
TI  - Sinigrin and Its Therapeutic Benefits.
AB  - Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a natural aliphatic
      glucosinolate present in plants of the Brassicaceae family, such as broccoli and
      brussels sprouts, and the seeds of Brassica nigra (mustard seeds) which contain
      high amounts of sinigrin. Since ancient times, mustard has been used by mankind
      for its culinary, as well as medicinal, properties. It has been systematically
      described and evaluated in the classical Ayurvedic texts. Studies conducted on
      the pharmacological activities of sinigrin have revealed anti-cancer,
      antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing
      properties and biofumigation. This current review will bring concise information
      about the known therapeutic activities of sinigrin. However, the information on
      known biological activities is very limited and, hence, further studies still
      need to be conducted and its molecular mechanisms also need to be explored. This
      review on the therapeutic benefits of sinigrin can summarize current knowledge
      about this unique phytocompounds. 

PMID- 27043506
TI  - Aroylhydrazone Cu(II) Complexes in keto Form: Structural Characterization and
      Catalytic Activity towards Cyclohexane Oxidation.
AB  - The reaction of the Schiff base (3,5-di-tert-butyl-2-hydroxybenzylidene)-2
      hydroxybenzohydrazide (H3L) with a copper(II) salt of a base of a strong acid,
      i.e., nitrate, chloride or sulphate, yielded the mononuclear complexes
      [Cu(H2L)(NO3)(H2O)] (1), [Cu(H2L)Cl].2MeOH (2) and the binuclear complex
      [{Cu(H2L)}2(u-SO4)].2MeOH (3), respectively, with H2L(-) in the keto form.
      Compounds 1-3 were characterized by elemental analysis, Infrared (IR)
      spectroscopy, Electrospray Ionisation Mass Spectrometry (ESI-MS) and single
      crystal X-ray crystallography. All compounds act as efficient catalysts towards
      the peroxidative oxidation of cyclohexane to cyclohexyl hydroperoxide,
      cyclohexanol and cyclohexanone, under mild conditions. In the presence of an acid
      promoter, overall yields (based on the alkane) up to 25% and a turnover number
      (TON) of 250 (TOF of 42 h(-1)) after 6 h, were achieved.

PMID- 27043507
TI  - Yeast Extract and Silver Nitrate Induce the Expression of Phenylpropanoid
      Biosynthetic Genes and Induce the Accumulation of Rosmarinic Acid in Agastache
      rugosa Cell Culture.
AB  - The present study aimed to investigate the role of yeast extract and silver
      nitrate on the enhancement of phenylpropanoid pathway genes and accumulation of
      rosmarinic acid in Agastache rugosa cell cultures. The treatment of cell cultures
      with yeast extract (500 mg/L) and silver nitrate (30 mg/L) for varying times
      enhanced the expression of genes in the phenylpropanoid pathway and the
      production of rosmarinic acid. The results indicated that the expression of RAS
      and HPPR was proportional to the amount of yeast extract and silver nitrate. The
      transcript levels of HPPR under yeast extract treatment were 1.84-, 1.97-, and
      2.86-fold higher than the control treatments after 3, 6, and 12 h, respectively,
      whereas PAL expression under silver nitrate treatment was 52.31-fold higher than
      in the non-treated controls after 24 h of elicitation. The concentration of
      rosmarinic acid was directly proportional to the concentration of the applied
      elicitors. Yeast extract supplementation documented the highest amount of
      rosmarinic acid at 4.98 mg/g, whereas silver nitrate addition resulted in a
      comparatively lower amount of rosmarinic acid at 0.65 mg/g. In conclusion,
      addition of yeast extract to the cell cultures enhanced the accumulation of
      rosmarinic acid, which was evidenced by the expression levels of the
      phenylpropanoid biosynthetic pathway genes in A. rugosa. 

PMID- 27043508
TI  - Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and
      Triazine Dendrimers.
AB  - Triazine and PAMAM dendrimers of similar size and number of cationic surface
      groups were compared for their ability to promote platelet aggregation. Triazine
      dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in
      surface groups 16-256. PAMAM dendrimers selected for comparison included G3 (7
      kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). The treatment of
      human platelet-rich plasma (PRP) with low generation triazine dendrimers (0.01-1
      uM) did not show any significant effect in human platelet aggregation in vitro;
      however, the treatment of PRP with larger generations promotes an effective
      aggregation. These results are in agreement with studies performed with PAMAM
      dendrimers, where large generations promote aggregation. Triazine dendrimers
      promote aggregation less aggressively than PAMAM dendrimers, a factor attributed
      to differences in cationic charge or the formation of supramolecular assemblies
      of dendrimers. 

PMID- 27043509
TI  - Synthesis of Novel Quaternary Ammonium Salts and Their in Vitro Antileishmanial
      Activity and U-937 Cell Cytotoxicity.
AB  - This work describes the synthesis of a series of quaternary ammonium salts and
      the assessment of their in vitro antileishmanial activity and cytotoxicity. A
      preliminary discussion on a structure-activity relationship of the compounds is
      also included. Three series of quaternary ammonium salts were prepared: (i)
      halomethylated quaternary ammonium salts (series I); (ii) non-halogenated
      quaternary ammonium salts (series II) and (iii) halomethylated choline analogs
      (series III). Assessments of their in vitro cytotoxicity in human promonocytic
      cells U-937 and antileishmanial activity in axenic amastigotes of L. (Viannia)
      panamensis (M/HOM/87/UA140-pIR-eGFP) were carried out using the MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) micromethod.
      Antileishmanial activity was also tested in intracellular amastigotes of L. (V)
      panamensis using flow cytometry. High toxicity for human U937 cells was found
      with most of the compounds, which exhibited Lethal Concentration 50 (LC50) values
      in the range of 9 to 46 MUg/mL. Most of the compounds evidenced antileishmanial
      activity. In axenic amastigotes, the antileishmanial activity varied from 14 to
      57 MUg/mL, while in intracellular amastigotes their activity varied from 17 to 50
      MUg/mL. N-Chloromethyl-N,N-dimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide
      (1a), N-iodomethyl-N,N-dimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide
      (2a), N,N,N-trimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (3a) and N,N,N
      trimethyl-N-(5,5-diphenylpent-4-en-1-yl)ammonium iodide (3b) turned out to be the
      most active compounds against intracellular amastigotes of L. (V) panamensis,
      with EC50 values varying between 24.7 for compound 3b and 38.4 MUg/mL for
      compound 1a. Thus, these compounds represents new "hits" in the development of
      leishmanicidal drugs. 

PMID- 27043510
TI  - Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged
      Black Garlic Extracts.
AB  - Numerous studies have demonstrated that aged black garlic (ABG) has strong anti
      oxidant activity. Little is known however regarding the anti-inflammatory
      activity of ABG. This study was performed to identify and compare the anti
      oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh
      raw garlic (FRG) extract (FRGE). In addition, we investigated which components
      are responsible for the observed effects. Hydrogen peroxide (H2O2) and
      lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory
      stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging
      activities and low ROS generation in RAW264.7 cells compared with FRGE. However,
      inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was
      stronger than that by ABGE. FRGE reduced PGE2, NO, IL-6, IL-1beta, LTD4, and LTE4
      production in LPS-activated RAW264.7 cells more than did ABGE. The combination of
      FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant
      in ABGE than in FRGE, decreased the anti-inflammatory activity compared with
      FRGE. FRGE-induced inhibition of NF-kappaB activation and pro-inflammatory gene
      expression was blocked by combination with sugars. The lower anti-inflammatory
      activity in ABGE than FRGE could result from the presence of sugars. Our results
      suggest that ABGE might be helpful for the treatment of diseases mediated
      predominantly by ROS.

PMID- 27043511
TI  - Plectranthus amboinicus (Lour.) Spreng: Botanical, Phytochemical, Pharmacological
      and Nutritional Significance.
AB  - Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the
      family Lamiaceae which occurs naturally throughout the tropics and warm regions
      of Africa, Asia and Australia. This herb has therapeutic and nutritional
      properties attributed to its natural phytochemical compounds which are highly
      valued in the pharmaceutical industry. Besides, it has horticultural properties
      due to its aromatic nature and essential oil producing capability. It is widely
      used in folk medicine to treat conditions like cold, asthma, constipation,
      headache, cough, fever and skin diseases. The leaves of the plant are often eaten
      raw or used as flavoring agents, or incorporated as ingredients in the
      preparation of traditional food. The literature survey revealed the occurrence 76
      volatiles and 30 non-volatile compounds belonging to different classes of
      phytochemicals such as monoterpenoids, diterpenoids, triterpenoids,
      sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies
      have cited numerous pharmacological properties including antimicrobial,
      antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal,
      antioxidant and analgesic activities. Also, it has been found to be effective
      against respiratory, cardiovascular, oral, skin, digestive and urinary diseases.
      Yet, scientific validation of many other traditional uses would be appreciated,
      mainly to discover and authenticate novel bioactive compounds from this herb.
      This review article provides comprehensive information on the botany,
      phytochemistry, pharmacology and nutritional importance of P. amboinicus
      essential oil and its various solvent extracts. This article allows researchers
      to further explore the further potential of this multi-utility herb for various
      biomedical applications. 

PMID- 27043512
TI  - Furostanol and Spirostanol Saponins from Tribulus terrestris.
AB  - Twelve new steroidal saponins, including eleven furostanol saponins, terrestrinin
      J-T (1-11), and one spirostanol saponin, terrestrinin U (12), together with seven
      known steroidal saponins 13-19 were isolated from T. terrestris. The structures
      of the new compounds were established on the basis of spectroscopic data,
      including 1D and 2D NMR and HRESIMS, and comparisons with published data. 

PMID- 27043513
TI  - Effect of Different Pretreatment Methods on Birch Outer Bark: New Biorefinery
      Routes.
AB  - A comparative study among different pretreatment methods used for the
      fractionation of the birch outer bark components, including steam explosion,
      hydrothermal and organosolv treatments based on the use of ethanol/water media,
      is reported. The residual solid fractions have been characterized by ATR-FTIR,
      (13)C-solid-state NMR and morphological alterations after pretreatment were
      detected by scanning electron microscopy. The general chemical composition of the
      untreated and treated bark including determination of extractives, suberin,
      lignin and monosaccharides was also studied. Composition of the residual solid
      fraction and relative proportions of different components, as a function of the
      processing conditions, could be established. Organosolv treatment produces a
      suberin-rich solid fraction, while during hydrothermal and steam explosion
      treatment cleavage of polysaccharide bonds occurs. This work will provide a
      deeper fundamental knowledge of the bark chemical composition, thus increasing
      the utilization efficiency of birch outer bark and may create possibilities to up
      scale the fractionation processes. 

PMID- 27043514
TI  - On the High Sensitivity of the Electronic States of 1 nm Gold Particles to
      Pretreatments and Modifiers.
AB  - In this paper, the effect of modifiers and pretreatments on the electronic states
      of 1 nm gold nanoparticles (AuNPs) supported on silica was systematically
      studied. AuNPs deposited on silica (particle size of 2-4 nm) modified with Ce, La
      and Fe oxides, were studied by FTIR of adsorbed CO after different redox
      treatments at 100, 300 and 500  degrees C. This study was conducted at room
      temperature to allow detecting the electronic states of gold, which is more
      likely involved in CO oxidation at the same temperature. AuNP size distribution
      was measured by HRTEM. It is shown that the electronic state of gold species
      (Aun(delta-), Au0, Aun(delta+), Au+) in 1 nm AuNPs is sensitive to the modifier
      as well as to the temperatures of redox pretreatments. Supports modified with the
      same additives but containing larger AuNPs (~3, 4, 5, and 7 nm) were also
      studied. They showed that Au0 remains stable irrespective of additives and redox
      pretreatments, indicating no significant effect of such treatments on the
      electronic properties of larger AuNPs. Samples with a predominant AuNP size of 2
      nm are an intermediate case between these two groups of materials. 

PMID- 27043515
TI  - Identification of Oxygenated Fatty Acid as a Side Chain of Lipo-Alkaloids in
      Aconitum carmichaelii by UHPLC-Q-TOF-MS and a Database.
AB  - Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum
      species. Structurally, they contain an aconitane skeleton and one or two fatty
      acid moieties of 3-25 carbon chains with 1-6 unsaturated degrees. Analysis of the
      lipo-alkaloids in roots of Aconitum carmichaelii resulted in the isolation of six
      known pure lipo-alkaloids (A1-A6) and a lipo-alkaloid mixture (A7). The mixture
      shared the same aconitane skeleton of 14-benzoylmesaconine, but their side chains
      were determined to be 9-hydroxy-octadecadienoic acid, 13-hydroxy-octadecadienoic
      acid and 10-hydroxy-octadecadienoic acid, respectively, by MS/MS analysis after
      alkaline hydrolysis. To our knowledge, this is the first time of the reporting of
      the oxygenated fatty acids as the side chains in naturally-occurring lipo
      alkaloids. In order to identify more lipo-alkaloids, a compound database was
      established based on various combinations between the aconitane skeleton and the
      fatty acid chain, and then, the identification of lipo-alkaloids was conducted
      using the database, UHPLC-Q-TOF-MS and MS/MS. Finally, 148 lipo-alkaloids were
      identified from A. carmichaelii after intensive MS/MS analysis, including 93
      potential new compounds and 38 compounds with oxygenated fatty acid moieties. 

PMID- 27043516
TI  - Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A
      Metabolomics Investigation.
AB  - BACKGROUND: Previous studies suggested that nucleotides were beneficial for liver
      function, lipid metabolism and so on. The present study aimed to investigate the
      metabolic response of dietary nucleotides supplementation in alcohol-induced
      liver injury rats. METHODS: Five groups of male Wistar rats were used: normal
      control group (basal diet, equivalent distilled water), alcohol control group
      (basal diet, 50% alcohol (v/v)), dextrose control group (basal diet, isocaloric
      amount of dextrose), and 0.04% and 0.16% nucleotides groups (basal diet
      supplemented with 0.4 g and 1.6 g nucleotides kg(-1) respectively, 50% alcohol
      (v/v)). The liver injury was measured through traditional liver enzymes,
      expression of oxidative stress markers and histopathological examination. Ultra
      performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC
      Q-TOF-MS) was applied to identify liver metabolite profiles. RESULTS: Nucleotides
      supplementation prevented the progression of hepatocyte steatosis. The levels of
      total proteins, globulin, alanine aminotransferase, aspartate aminotransferase,
      total cholesterol triglyceride, as well as the oxidative stress markers altered
      by alcohol, were improved by nucleotides supplementation. Elevated levels of
      liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and
      taurodeoxycholic acid), as well as lipids (stearic acid, palmitic acid, oleic
      acid, phosphatidylcholine, and lysophosphatidylethanolamine) in alcohol-treated
      rats were reversed by nucleotides supplementation. In addition, supplementation
      with nucleotides could increase the levels of amino acids, including valyl
      Leucine, L-leucine, alanyl-leucine and L-phenylalanine. CONCLUSION: These data
      indicate potential biomarkers and confirm the benefit of dietary nucleotides on
      alcoholic liver injury.

PMID- 27043517
TI  - sym-Trisubstituted 1,3,5-Triazine Derivatives as Promising Organic Corrosion
      Inhibitors for Steel in Acidic Solution.
AB  - Triazine derivatives, namely, 2,4,6-tris(quinolin-8-yloxy)-1,3,5-triazine (T3Q),
      N2,N4,N6-tris(pyridin-2-ylmethyl)-1,3,5-triazine-2,4,6-triamine (T3AMPy) and
      2,2',2''-[(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)] tris(ethan-1-ol) (T3EA)
      were synthesized and their inhibition of steel corrosion in hydrochloric acid
      solution was investigated using electrochemical techniques. The corrosion
      protection of the prepared compounds increased with increasing concentration and
      reached up to 98% at 250 ppm. The adsorption of T3Q, T3AMPy, and T3EA on the
      steel surface was in accordance with the Langmuir adsorption isotherm. The
      electrochemical results revealed that T3Q, T3AMPy and T3EA act as excellent
      organic inhibitors and can labeled as mixed type inhibitors. The efficiencies of
      the tested compounds were affected by the nature of the side chain present in the
      triazine ring, where T3EA gave the least inhibition while T3Q and T3AMPy gave
      higher and almost the same inhibition effects. The inhibition efficiencies
      obtained from the different electrochemical techniques were in good agreement. 

PMID- 27043518
TI  - Synthesis and Structure-Activity Relationship Analysis of 5-HT7 Receptor
      Antagonists: Piperazin-1-yl Substituted Unfused Heterobiaryls.
AB  - A series of piperazin-1-yl substituted unfused heterobiaryls was synthesized as
      ligands of the 5-HT7 receptors. The goal of this project was to elucidate the
      structural features that affect the 5-HT7 binding affinity of this class of
      compounds represented by the model ligand 4-(3-furyl)-2-(4-methylpiperazin-1
      yl)pyrimidine (2). The SAR studies included systematical structural changes of
      the pyrimidine core moiety in 2 to quinazoline, pyridine and benzene, changes of
      the 3-furyl group to other heteroaryl substituents, the presence of various
      analogs of the 4-methylpiperazin-1-yl group, as well as additional substitutions
      at positions 5 and 6 of the pyrimidine. Substitution of position 6 of the
      pyrimidine in the model ligand with an alkyl group results in a substantial
      increase of the binding affinity (note a change in position numbers due to the
      nomenclature rules). It was also demonstrated that 4-(3-furyl) moiety is crucial
      for the 5-HT7 binding affinity of the substituted pyrimidines, although, the
      pyrimidine core can be replaced with a pyridine ring without a dramatic loss of
      the binding affinity. The selected ethylpyrimidine (12) and butylpyrimidine (13)
      analogs of high 5-HT7 binding affinity showed antagonistic properties in cAMP
      functional test and varied selectivity profile-compound 12 can be regarded as a
      dual 5-HT7/5-HT2AR ligand, and 13 as a multi-receptor (5-HT7, 5-HT2A, 5-HT6 and
      D2) agent. 

PMID- 27043519
TI  - Photophysical Characterization and in Vitro Phototoxicity Evaluation of
      5,10,15,20-Tetra(quinolin-2-yl)porphyrin as a Potential Sensitizer for
      Photodynamic Therapy.
AB  - Photodynamic therapy (PDT) is a selective and minimally invasive therapeutic
      approach, involving the combination of a light-sensitive compound, called a
      photosensitizer (PS), visible light and molecular oxygen. The interaction of
      these per se harmless agents results in the production of reactive species. This
      triggers a series of cellular events that culminate in the selective destruction
      of cancer cells, inside which the photosensitizer preferentially accumulates. The
      search for ideal PDT photosensitizers has been a very active field of research,
      with a special focus on porphyrins and porphyrin-related macrocycle molecules.
      The present study describes the photophysical characterization and in vitro
      phototoxicity evaluation of 5,10,15,20-tetra(quinolin-2-yl)porphyrin (2-TQP) as a
      potential PDT photosensitizer. Molar absorption coefficients were determined from
      the corresponding absorption spectrum, the fluorescence quantum yield was
      calculated using 5,10,15,20-tetraphenylporphyrin (TPP) as a standard and the
      quantum yield of singlet oxygen generation was determined by direct
      phosphorescence measurements. Toxicity evaluations (in the presence and absence
      of irradiation) were performed against HT29 colorectal adenocarcinoma cancer
      cells. The results from this preliminary study show that the hydrophobic 2-TQP
      fulfills several critical requirements for a good PDT photosensitizer, namely a
      high quantum yield of singlet oxygen generation (Phi? 0.62), absence of dark
      toxicity and significant in vitro phototoxicity for concentrations in the
      micromolar range. 

PMID- 27043520
TI  - Physicochemical Properties of Defatted Rambutan (Nephelium lappaceum) Seed Flour
      after Alkaline Treatment.
AB  - Rambutan seeds were subjected to SC-CO2 extraction at 35 MPa, 45  degrees C to
      obtain defatted rambutan seed flour. Its physicochemical properties before and
      after treatment with alkali solution using 0.075 N NaOH were investigated. Alkali
      treated flour had a significant increment in bulk density, swelling power, water
      adsorption capacity, emulsion capacity and stability but a reduction in
      turbidity, solubility and oil absorption capacity. Pasting measurements showed
      peak viscosity, breakdown, setback and final viscosity increased significantly
      for the alkali-treated flour, while pasting temperature decreased. The alkaline
      treatment decreased the least gelation concentration, but increased the apparent
      viscosity.

PMID- 27043521
TI  - Labdane Diterpenes from the Fruits of Sinopodophyllum emodi.
AB  - Two new labdane diterpenes, sinoditerpene A (1) and B (2), were isolated from the
      fruits of Sinopodophyllum emodi, along with two known analogues 3 and 4. Their
      structures were established on the basis of extensive spectroscopic analysis. The
      isolation of compounds 1-4 represents the first report of diterpenes from the
      genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were
      evaluated in comparison with 5-fluorouracil against the MCF-7 and HepG2 cell
      lines, towards which 3 showed more potent cytotoxicity. 

PMID- 27043522
TI  - A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3
      d]pyrimidine-diones in Water: A Triply Green Synthesis.
AB  - A novel one pot synthesis of pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine-diones,
      via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate,
      and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium
      acetate catalyzed via both of heterogeneous and homogeneous catalysis in water,
      is reported. 

PMID- 27043523
TI  - Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating
      Oxidative Stress and Reducing Inflammatory Response.
AB  - Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has
      been reported to prevent liver injuries induced by various chemicals or toxins.
      Our recent study suggested that silymarin induces hepatic synthesis of
      glutathione by increasing cysteine availability, which may consequently
      contribute to increased antioxidant capacity of the liver. In the present study,
      we investigated the effects of silymarin on acute liver injury induced by
      restraint stress. Silymarin (100 mg/kg) was orally administered to BALB/c mice
      every 12 h (3 times in total). After the last dose, mice were subjected to
      restraint stress for 6 h, and serum levels of aspartate and alanine
      aminotransferases, and hepatic levels of lipid peroxidation were determined.
      Hepatic levels of sulfur-containing metabolites such as methionine, S
      adenosylmethionine, cysteine, and glutathione were also measured. The level of
      pro-inflammatory mediators in both liver and serum was determined. To study the
      mechanism of the effects of silymarin, we assessed Jun N-terminal kinase (JNK)
      activation and apoptotic signaling. Restraint stress induced severe oxidative
      stress and increased mRNA levels of pro-inflammatory mediators; both effects of
      restraint stress were significantly inhibited by silymarin. Moreover,
      administration of silymarin significantly prevented acute liver injury induced by
      restraint stress by blocking JNK activation and subsequently apoptotic signaling.
      In conclusion, these results suggest that the inhibition of restraint stress
      induced liver injury by silymarin is due at least in part to its anti-oxidant
      activity and its ability to suppress the inflammatory response. 

PMID- 27043524
TI  - Two Additional New Compounds from the Marine-Derived Fungus Pseudallescheria
      ellipsoidea F42-3.
AB  - Two additional new compounds, pseudellone D (1) and (5S,6S)
      dihydroxylasiodiplodin (3), along with the two known compounds lasiodipline F
      (2), (5S)-hydroxylasiodiplodin (4) were isolated from the marine-derived fungus
      Pseudallescheria ellipsoidea F42-3 associated with the soft coral Lobophytum
      crassum. Their structures, including absolute configurations, were elucidated on
      the basis of the corresponding spectroscopic data and electronic circular
      dichroism (ECD) spectra. 

PMID- 27043525
TI  - Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic
      Stroke.
AB  - Clinically-informative biomarkers of ischemic stroke are needed for rapid
      diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1
      UP), a novel peptide biomarker, was identified and quantified by multiple
      reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of
      94 patients in the ischemic stroke group and 37 patients in the non-stroke group
      were analyzed for the levels of total APOA1-UP, low density lipoprotein
      cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol
      (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14
      (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the
      ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was
      independently correlated with the presence of ischemic stroke by multivariate
      logistic regression analysis (p < 0.0001). From the receiver operating
      characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the
      optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a
      sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of
      HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is
      a diagnostic biomarker candidate for ischemic stroke in the early stage. 

PMID- 27043526
TI  - Aripiprazole and Haloperidol Activate GSK3beta-Dependent Signalling Pathway
      Differentially in Various Brain Regions of Rats.
AB  - Aripiprazole, a dopamine D2 receptor (D2R) partial agonist, possesses a unique
      clinical profile. Glycogen synthase kinase 3beta (GSK3beta)-dependent signalling
      pathways have been implicated in the pathophysiology of schizophrenia and
      antipsychotic drug actions. The present study examined whether aripiprazole
      differentially affects the GSK3beta-dependent signalling pathways in the
      prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in
      comparison with haloperidol (a D2R antagonist) and bifeprunox (a D2R partial
      agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox
      (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week.
      The levels of protein kinase B (Akt), p-Akt, GSK3beta, p-GSK3beta, dishevelled
      (Dvl)-3, and beta-catenin were measured by Western Blots. Aripiprazole increased
      GSK3beta phosphorylation in the PFC and NAc, respectively, while haloperidol
      elevated it in the NAc only. However, Akt activity was not changed by any of
      these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox,
      increased the expression of Dvl-3 and beta-catenin in the NAc. The present study
      suggests that activation of GSK3beta phosphorylation in the PFC and NAc may be
      involved in the clinical profile of aripiprazole; additionally, aripiprazole can
      increase GSK3beta phosphorylation via the Dvl-GSK3beta-beta-catenin signalling
      pathway in the NAc, probably due to its relatively low intrinsic activity at
      D2Rs. 

PMID- 27043527
TI  - TOR Pathway-Mediated Juvenile Hormone Synthesis Regulates Nutrient-Dependent
      Female Reproduction in Nilaparvata lugens (Stal).
AB  - The "target of rapamycin" (TOR) nutritional signaling pathway and juvenile
      hormone (JH) regulation of vitellogenesis has been known for a long time.
      However, the interplay between these two pathways regulating vitellogenin (Vg)
      expression remains obscure. Here, we first demonstrated the key role of amino
      acids (AAs) in activation of Vg synthesis and egg development in Nilaparvata
      lugens using chemically defined artificial diets. AAs induced the expression of
      TOR and S6K (S6 kinase), whereas RNAi-mediated silencing of these two TOR pathway
      genes and rapamycin application strongly inhibited the AAs-induced Vg synthesis.
      Furthermore, knockdown of Rheb (Ras homologue enriched in brain), TOR, S6K and
      application of rapamycin resulted in a dramatic reduction in the mRNA levels of
      jmtN (juvenile hormone acid methyltransferase, JHAMT). Application of JH III on
      the RNAi (Rheb and TOR) and rapamycin-treated females partially rescued the Vg
      expression. Conversely, knockdown of either jmtN or met (methoprene-tolerant, JH
      receptor) and application of JH III had no effects on mRNA levels of Rheb, TOR
      and S6K and phosphorylation of S6K. In summary, our results demonstrate that the
      TOR pathway induces JH biosynthesis that in turn regulates AAs-mediated Vg
      synthesis in N. lugens. 

PMID- 27043529
TI  - Two omega-3 FADs Are Associated with Peach Fruit Volatile Formation.
AB  - Aroma-related volatiles, together with sugars and acids, play an important role
      in determining fruit flavor quality. Characteristic volatiles of peach fruit are
      mainly derived from fatty acids such as linoleic acid (18:2) and linolenic acid
      (18:3). In the present study, six genes encoding fatty acid desaturases (FAD)
      were cloned, including two omega-6 FAD genes (PpFAD2, PpFAD6) and four omega-3
      FAD genes (PpFAD3-1, PpFAD3-2, PpFAD7 and PpFAD8). Heterologous expression of
      peach FADs in tobacco plants showed that PpFAD3-1, and PpFAD3-2 significantly
      reduced contents of 18:2, and accumulated significant higher levels of 18:3. In
      the case of volatiles, transgenic plants produced lower concentrations of hexanal
      and higher levels of (E)-2-hexenal. Consequently, the ratio of the (E)-2-hexenal
      and hexanal was about 5- and 3-fold higher than that of wild type (WT) in PpFAD3
      1 and PpFAD3-2 transformants, respectively. No significant changes in volatile
      profiles were observed in transgenic plants overexpressing the four other peach
      FAD genes. Real-time quantitative polymerase chain reaction (qPCR) analysis
      showed that ripe fruit had high PpFAD3-1 and low PpFAD3-2 transcript levels. In
      contrast, high PpFAD3-2 and low PpFAD3-1 transcript levels were observed in young
      fruit. These results indicate a temporal regulation of these two omega-3 FADs
      during development and ripening, influencing peach fruit volatile formation. 

PMID- 27043528
TI  - Mechanism of Sleep Disturbance in Children with Atopic Dermatitis and the Role of
      the Circadian Rhythm and Melatonin.
AB  - Sleep disturbance is common in children with atopic dermatitis (AD). It is a
      major factor leading to impaired quality of life in these patients and could have
      negative effects on neurocognitive function and behavior. However, the
      pathophysiology of sleep disturbance in children with AD is poorly understood,
      and there is no consensus on how to manage sleep problems in these patients.
      Pruritus and scratching could lead to sleep disruption but is unlikely the sole
      etiology. The circadian rhythm of cytokines, the immune system, and skin
      physiology such as transcutaneous water loss and skin blood flow might also play
      a role. Recent studies have suggested that melatonin could also be involved due
      to its multiple effects on sleep, immunomodulation, and anti-oxidant ability.
      Environmental factors should also be considered. In this review, we summarize the
      current understanding of the pathophysiology of sleep disturbance in children
      with AD, and discuss possible therapeutic implications. 

PMID- 27043530
TI  - Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying
      Mechanisms.
AB  - Leukemia is the most common cancer in children, representing 30% of all childhood
      cancers. The disease arises from recurrent genetic insults that block
      differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives
      uncontrolled proliferation and survival of the differentiation-blocked clone.
      Pediatric leukemia is phenotypically and genetically heterogeneous with an
      obscure etiology. The interaction between genetic factors and environmental
      agents represents a potential etiological driver. Although information is
      limited, the principal toxic mechanisms of potential leukemogenic agents (e.g.,
      etoposide, benzene metabolites, bioflavonoids and some pesticides) include
      topoisomerase II inhibition and/or excessive generation of free radicals, which
      may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs.
      Chromosomal rearrangements (duplications, deletions and translocations) may occur
      if these lesions are not properly repaired. The initiating hit usually occurs in
      utero and commonly leads to the expression of oncogenic fusion proteins.
      Subsequent cooperating hits define the disease latency and occur after birth and
      may be of a genetic, epigenetic or immune nature (i.e., delayed infection
      mediated immune deregulation). Here, we review the available experimental and
      epidemiological evidence linking pesticide exposure to infant and childhood
      leukemia and provide a mechanistic basis to support the association, focusing on
      early initiating molecular events. 

PMID- 27043532
TI  - Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the
      Relationship to Psychiatric Assessments.
AB  - Chronic alcohol use alters adaptive immunity and cytokine activity influencing
      immunological and hormone responses, inflammation, and wound healing. Brain
      cytokine disturbances may impact neurological function, mood, cognition and
      traits related to alcoholism including impulsiveness. We examined the
      relationship between plasma cytokine levels and self-rated psychiatric symptoms
      in 40 adult males (mean age 51 +/- 6 years; range 33-58 years) with current
      alcohol dependence and 30 control males (mean age 48 +/- 6 years; range 40-58
      years) with no history of alcoholism using multiplex sandwich immunoassays with
      the Luminex magnetic-bead based platform. Log-transformed cytokine levels were
      analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt
      Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory
      cytokines (interferon gamma-induced protein-10 (IP-10); monocyte chemoattractant
      protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted
      (RANTES)) were significantly elevated in alcoholism compared to controls while
      bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony
      stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene
      (GRO)) were significantly reduced. GRO and RANTES levels were positively
      correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were
      positively correlated with SCL-90R scale scores (p < 0.05). Elevated inflammatory
      mediators in alcoholism may influence brain function leading to increased
      impulsiveness and/or phobia. The novel association between RANTES and GRO and
      impulsivity phenotype in alcoholism should be further investigated in alcoholism
      and psychiatric conditions with core impulsivity and anxiety phenotypes lending
      support for therapeutic intervention. 

PMID- 27043531
TI  - Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF) in a
      d-Galactose-Induced Aging Heart.
AB  - Aging, a natural biological/physiological phenomenon, is accelerated by reactive
      oxygen species (ROS) accumulation and identified by a progressive decrease in
      physiological function. Several studies have shown a positive relationship
      between aging and chronic heart failure (HF). Cardiac apoptosis was found in age
      related diseases. We used a traditional Chinese medicine, Alpinate Oxyphyllae
      Fructus (AOF), to evaluate its effect on cardiac anti-apoptosis and pro-survival.
      Male eight-week-old Sprague-Dawley (SD) rats were segregated into five groups:
      normal control group (NC), d-Galactose-Induced aging group (Aging), and AOF of 50
      (AL (AOF low)), 100 (AM (AOF medium)), 150 (AH (AOF high)) mg/kg/day. After eight
      weeks, hearts were measured by an Hematoxylin-Eosin (H&E) stain, Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-assays and Western
      blotting. The experimental results show that the cardiomyocyte apoptotic pathway
      protein expression increased in the d-Galactose-Induced aging groups, with dose
      dependent inhibition in the AOF treatment group (AL, AM, and AH). Moreover, the
      expression of the pro-survival p-Akt (protein kinase B (Akt)), Bcl-2 (B-cell
      lymphoma 2), anti-apoptotic protein (Bcl-xL) protein decreased significantly in
      the d-Galactose-induced aging group, with increased performance in the AOF
      treatment group with levels of p-IGFIR and p-PI3K (Phosphatidylinositol-3' kinase
      (PI3K)) to increase by dosage and compensatory performance. On the other hand,
      the protein of the Sirtuin 1 (SIRT1) pathway expression decreased in the aging
      groups and showed improvement in the AOF treatment group. Our results suggest
      that AOF strongly works against ROS-induced aging heart problems. 

PMID- 27043534
TI  - Restricted Gene Flow for Gadus macrocephalus from Yellow Sea Based on
      Microsatellite Markers: Geographic Block of Tsushima Current.
AB  - The Pacific cod Gadus macrocephalus is a demersal, economically important fish in
      the family Gadidae. Population genetic differentiation of Pacific cod was
      examined across its northwestern Pacific range by screening variation of eight
      microsatellite loci in the present study. All four populations exhibited high
      genetic diversity. Pairwise fixation index (Fst) suggested a moderate to high
      level of genetic differentiation among populations. Population of the Yellow Sea
      (YS) showed higher genetic difference compared to the other three populations
      based on the results of pairwise Fst, three-dimensional factorial correspondence
      analysis (3D-FCA) and STRUCTURE, which implied restricted gene flow among them.
      Wilcoxon signed rank tests suggested no significant heterozygosity excess and no
      recent genetic bottleneck events were detected. Microsatellite DNA is an
      effective molecular marker for detecting the phylogeographic pattern of Pacific
      cod, and these Pacific cod populations should be three management units. 

PMID- 27043535
TI  - Exploring Erythropoietin and G-CSF Combination Therapy in Chronic Stroke
      Patients.
AB  - Erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) are known
      to have neuroprotective actions. Based on previous reports showing the
      synergistic effects of EPO+G-CSF combination therapy in experimental models, we
      investigated the safety of EPO+G-CSF combination therapy in patients with chronic
      stroke. In a pilot study, 3 patients were treated with EPO and G-CSF for 5
      consecutive days, with follow-up on day 30. In an exploratory double-blind study,
      6 patients were allocated to treatment with either EPO+G-CSF or placebo.
      Treatment was applied once a day for 5 days per month over 3 months. Participants
      were followed up for 6 months. To substantiate safety, vital signs, adverse
      events, and hematological values were measured on days 0, 5, and 30 in each cycle
      and on day 180. Functional outcomes were determined on day 0 and 180. In the
      laboratory measurements, EPO+G-CSF combination therapy significantly elevated
      erythropoietin, CD34+ hematopoietic stem cells, white blood cells, and
      neutrophils on day 5 of each cycle. There were no observations of serious adverse
      events. In the functional outcomes, the grip power of the dominant hand was
      increased in the EPO+G-CSF treatment group. In conclusion, this exploratory study
      suggests a novel strategy of EPO+G-CSF combination therapy for stroke patients. 

PMID- 27043536
TI  - Meta-Analysis on Associations of RGS1 and IL12A Polymorphisms with Celiac Disease
      Risk.
AB  - The pathogenesis of celiac disease (CD) has been related to polymorphisms in the
      regulator of G-protein signaling 1 (RGS1) and interleukin-12 A (IL12A) genes, but
      the existing findings are inconsistent. Our aim is to investigate the
      associations of two single-nucleotide polymorphisms (SNPs) (rs2816316 in RGS1 and
      rs17810546 in IL12A) with CD risk using meta-analysis. We searched PubMed and Web
      of Science on RGS1 rs2816316 and IL12A rs17810546 with CD risk. Odds ratio (OR)
      and 95% confidence interval (CI) of each SNP were estimated. All statistical
      analyses were performed on Stata 12.0. A total of seven studies were retrieved
      and analyzed. The available data indicated the minor allele C of rs2816316 was
      negatively associated with CD (C vs. A: OR = 0.77, 95% CI = 0.74-0.80), and a
      positive association was found for the minor allele G of rs17810546 (G vs. A: OR
      = 1.37, 95% CI = 1.31-1.43). The co-dominant model of genotype effect confirmed
      the significant associations between RGS1 rs2816316/IL12A rs17810546 and CD. No
      evidence of publication bias was observed. Our meta-analysis supports the
      associations of RGS1 and IL12A with CD and strongly calls for further studies to
      better understand the roles of RGS1 and IL12A in the pathogenesis of CD. 

PMID- 27043537
TI  - The Expression Profile of Complement Components in Podocytes.
AB  - Podocytes are critical for maintaining the glomerular filtration barrier and are
      injured in many renal diseases, especially proteinuric kidney diseases. Recently,
      reports suggested that podocytes are among the renal cells that synthesize
      complement components that mediate glomerular diseases. Nevertheless, the profile
      and extent of complement component expression in podocytes remain unclear. This
      study examined the expression profile of complement in podocytes under
      physiological conditions and in abnormal podocytes induced by multiple stimuli.
      In total, 23/32 complement component components were detected in podocyte by
      conventional RT-PCR. Both primary cultured podocytes and immortalized podocytes
      expressed the complement factors C1q, C1r, C2, C3, C7, MASP, CFI, DAF, CD59,
      C4bp, CD46, Protein S, CR2, C1qR, C3aR, C5aR, and Crry (17/32), whereas C4, CFB,
      CFD, C5, C6, C8, C9, MBL1, and MBL2 (9/32) complement factors were not expressed.
      C3, Crry, and C1q-binding protein were detected by tandem mass spectrometry.
      Podocyte complement gene expression was affected by several factors (puromycin
      aminonucleoside (PAN), angiotensin II (Ang II), interleukin-6 (IL-6), and
      transforming growth factor-beta (TGF-beta)). Representative complement components
      were detected using fluorescence confocal microscopy. In conclusion, primary
      podocytes express various complement components at the mRNA and protein levels.
      The complement gene expressions were affected by several podocyte injury factors.

PMID- 27043533
TI  - Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory
      and Anti-Oxidative Activities.
AB  - The liver is intimately connected to inflammation, which is the innate defense
      system of the body for removing harmful stimuli and participates in the hepatic
      wound-healing response. Sustained inflammation and the corresponding regenerative
      wound-healing response can induce the development of fibrosis, cirrhosis and
      eventually hepatocellular carcinoma. Oxidative stress is associated with the
      activation of inflammatory pathways, while chronic inflammation is found
      associated with some human cancers. Inflammation and cancer may be connected by
      the effect of the inflammation-fibrosis-cancer (IFC) axis. Chinese medicinal
      herbs display abilities in protecting the liver compared to conventional
      therapies, as many herbal medicines have been shown as effective anti
      inflammatory and anti-oxidative agents. We review the relationship between
      oxidative stress and inflammation, the development of hepatic diseases, and the
      hepatoprotective effects of Chinese medicinal herbs via anti-inflammatory and
      anti-oxidative mechanisms. Moreover, several Chinese medicinal herbs and
      composite formulae, which have been commonly used for preventing and treating
      hepatic diseases, including Andrographis Herba, Glycyrrhizae Radix et Rhizoma,
      Ginseng Radix et Rhizoma, Lycii Fructus, Coptidis Rhizoma, curcumin, xiao-cha-hu
      tang and shi-quan-da-bu-tang, were selected for reviewing their hepatoprotective
      effects with focus on their anti-oxidative and ant-inflammatory activities. This
      review aims to provide new insight into how Chinese medicinal herbs work in
      therapeutic strategies for liver diseases. 

PMID- 27043538
TI  - Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes.
AB  - Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of
      mutations in microRNA (miRNA) processing proteins suggest a pivotal role of
      miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of
      different subtypes and four normal kidney tissues using microarrays.
      Additionally, we determined the gene expression profile of 28 of these tumors to
      identify potentially correlated target genes and affected pathways. We identified
      85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal
      WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype.
      The hierarchical clustering of the samples, using either the miRNA or mRNA
      profile, showed the clear separation of WT from normal kidney samples, but the
      miRNA pattern yielded better separation of WT subtypes. A correlation analysis of
      the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely
      correlated expression, of which 2844 are potential interactions of miRNA and
      their predicted mRNA targets. We found significant upregulation of miRNAs-183, 
      301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the
      regressive subtype. We found marked deregulation of miRNAs regulating epithelial
      to mesenchymal transition, especially in the blastemal subtype, and miRNAs
      influencing chemosensitivity, especially in regressive subtypes. Further research
      is needed to assess the influence of preoperative chemotherapy and tumor
      infiltrating lymphocytes on the miRNA and mRNA patterns in WT. 

PMID- 27043539
TI  - Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory
      and Coagulation Pathways.
AB  - Thymoquinone (THQ) is a major component of black seeds. Given that both THQ and
      black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized
      that THQ will affect cancer-associated thrombosis (CAT), which is primarily
      triggered by tissue factor (TF) and inflammation. The effect of both black seed
      extracted and purchased ("pure") THQ on normal blood coagulation was tested with
      in vitro thromboelastography (TEG) and activated partial thromboplastin time
      (aPTT) coagulation assays. The effect of pure THQ on CAT was tested with aPTT
      assay using pancreatic cancer cell lines that are either positive or negative for
      TF, and with TEG assay using lipopolysaccharide as an inflammatory trigger.
      Additionally, the direct effect of THQ on the inactivation of factors IIa and Xa
      was assessed. Since TNF-alpha facilitates crosstalk between inflammation and
      thrombosis by triggering the NF-kappaB pathway, we tested THQ's ability to
      interfere with this communication with a luciferase assay. Both extracted and
      pure THQ had minimal effects on normal blood coagulation. Pure THQ reversed CAT
      initiated by both TF and inflammation to basal levels (p < 0.001).
      Mechanistically, while THQ had minimal to no effect on factor IIa and Xa
      inactivation, it strongly reduced the effects of TNF-alpha on NF-kappaB elements
      (p < 0.001). THQ has a minimal effect on basal coagulation and can reverse CAT in
      vitro, possibly by interfering with the crosstalk between inflammation and
      coagulation. This study suggests the utility of THQ as a preventative
      anticoagulant and/or as a supplement to existing chemotherapies and anticoagulant
      therapies. 

PMID- 27043540
TI  - pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting
      Delivery of Doxorubicin.
AB  - The tumor targetability and stimulus responsivity of drug delivery systems are
      crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting
      mixed micelles composed of a hyaluronic acid-glycyrrhetinic acid conjugate and a
      hyaluronic acid-l-histidine conjugate (HA-GA/HA-His) were prepared through
      ultrasonic dispersion. The formation and characterization of the mixed micelles
      were confirmed via 1H-NMR, particle size, and zeta potential measurements. The in
      vitro cellular uptake of the micelles was evaluated using human liver carcinoma
      (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was
      investigated in vitro and in vivo. Results indicated that the DOX-loaded HA-GA/HA
      His micelles showed a pH-dependent controlled release and were remarkably
      absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA-GA/HA-His
      micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles
      effectively inhibited tumor growth in H22 cell-bearing mice. These results
      suggest that the HA-GA/HA-His mixed micelles are a good candidate for drug
      delivery in the prevention and treatment of hepatocarcinoma. 

PMID- 27043541
TI  - Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer.
AB  - Due to high mortality rates of lung cancer, there is a need for identification of
      new, clinically useful markers, which improve detection of this tumor in early
      stage of disease. In the current study, serum peptide profiling was evaluated as
      a diagnostic tool for non-small cell lung cancer patients. The combination of the
      ZipTip technology with matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS) for the analysis of peptide pattern of cancer
      patients (n = 153) and control subjects (n = 63) was presented for the first
      time. Based on the observed significant differences between cancer patients and
      control subjects, the classification model was created, which allowed for
      accurate group discrimination. The model turned out to be robust enough to
      discriminate a new validation set of samples with satisfactory sensitivity and
      specificity. Two peptides from the diagnostic pattern for non-small cell lung
      cancer (NSCLC) were identified as fragments of C3 and fibrinogen alpha chain.
      Since ELISA test did not confirm significant differences in the expression of
      complement component C3, further study will involve a quantitative approach to
      prove clinical utility of the other proteins from the proposed multi-peptide
      cancer signature. 

PMID- 27043542
TI  - Exogenous C2 Ceramide Suppresses Matrix Metalloproteinase Gene Expression by
      Inhibiting ROS Production and MAPK Signaling Pathways in PMA-Stimulated Human
      Astroglioma Cells.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases,
      which play a pivotal role in invasion, migration, and angiogenesis of glioma.
      Therefore, controlling MMPs is potentially an important therapeutic strategy for
      glioma. In the present study, we found that exogenous cell-permeable short-chain
      C2 ceramide inhibits phorbol myristate acetate (PMA)-induced MMP-1, -3, and -9
      gene expressions in U87MG and U373MG human astroglioma cells. In addition, C2
      ceramide inhibited the protein secretion and enzymatic activities of MMP-1, -3,
      and -9. The Matrigel invasion assay and wound healing assay showed that C2
      ceramide suppresses the in vitro invasion and migration of glioma cells, which
      appears to be involved in strong inhibition of MMPs by C2 ceramide. Subsequent
      mechanistic studies revealed that C2 ceramide inhibits PMA-induced mitogen
      activated protein kinase (MAPK) phosphorylation and nuclear factor (NF)
      kappaB/activator protein (AP)-1 DNA binding activities. Furthermore, C2 ceramide
      significantly inhibited PMA-induced reactive oxygen species (ROS) production and
      NADPH oxidase 4 (NOX4) expression, and inhibition of ROS by diphenylene iodonium
      (DPI, NADPH oxidase inhibitor) mimicked the effects of C2 ceramide on MMP
      expression and NF-kappaB/AP-1 via inhibition of p38 MAPK. The results suggest C2
      ceramide inhibits MMP expression and glioma invasion, at least partly, by
      modulating ROS-p38 MAPK signaling axis and other MAPK signaling pathways. 

PMID- 27043543
TI  - Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls
      after Oral Fat Load.
AB  - BACKGROUND: Free fatty acid (FFA) metabolism can impact on metabolic conditions,
      such as obesity and nonalcoholic fatty liver disease (NAFLD). This work studied
      the increase in total FFA shown in NAFLD subjects to possibly characterize which
      fatty acids significantly accounted for the whole increase. METHODS: 21 patients
      with NAFLD were selected according to specified criteria. The control group
      consisted of nine healthy subjects. All subjects underwent an oral standard fat
      load. Triglycerides; cholesterol; FFA; glucose and insulin were measured every 2
      h with the determination of fatty acid composition of FFA. RESULTS: higher serum
      FFA levels in NAFLD subjects are mainly due to levels of oleic, palmitic and
      linoleic acids at different times. Significant increases were shown for
      docosahexaenoic acid, linolenic acid, eicosatrienoic acid, and arachidonic acid,
      although this was just on one occasion. In the postprandial phase, homeostatic
      model assessment HOMA index positively correlated with the omega3/omega6 ratio in
      NAFLD patients. CONCLUSIONS: the higher serum levels of FFA in NAFLD subjects are
      mainly due to levels of oleic and palmitic acids which are the most abundant
      circulating free fatty acids. This is almost exactly corresponded with
      significant increases in linoleic acid. An imbalance in the n-3/n-6 fatty acids
      ratio could modulate postprandial responses with more pronounced effects in
      insulin-resistant subjects, such as NAFLD patients.

PMID- 27043544
TI  - The Honolulu Liver Disease Cluster at the Medical Center: Its Mysteries and
      Challenges.
AB  - In 2013, physicians at the Honolulu Queen's Medical Center (QMC) noticed that
      seven liver disease patients reported the use of OxyELITE Pro (OEP), a widely
      consumed dietary supplement (DS). Assuming a temporal association between OEP use
      and disease, they argued that OEP was the cause of this mysterious cluster.
      Subsequent reexamination, however, has revealed that this QMC cohort is
      heterogeneous and not a cluster with a single agent causing a single disease. It
      is heterogeneous because patients used multiple DS's and drugs and because
      patients appeared to have suffered from multiple liver diseases: liver cirrhosis,
      liver failure by acetaminophen, hepatotoxicity by non-steroidal antiinflammatory
      drugs (NSAIDs), resolving acute viral hepatitis by hepatitis B virus (HBV),
      herpes simplex virus (HSV), and varicella zoster virus (VZV), and suspected
      hepatitis E virus (HEV). Failing to exclude these confounders and to consider
      more viable diagnoses, the QMC physicians may have missed specific treatment
      options in some of their patients. The QMC physicians unjustifiably upgraded
      their Roussel Uclaf Causality Assessment Method (RUCAM) causality scores so that
      all patients would appear to be "probable" for OEP. However, subsequent RUCAM
      reassessments by our group demonstrated a lack of causality for OEP in the
      evaluated QMC cases. The QMC's questionable approaches explain the extraordinary
      accumulation of suspected OEP cases at the QMC in Hawaii as single place, whereas
      similar cohorts were not published by any larger US liver center, substantiating
      that the problem is with the QMC. In this review article, we present and discuss
      new case data and critically evaluate upcoming developments of problematic
      regulatory assessments by the US Centers for Disease Control and Prevention
      (CDC), the Hawaii Department of Health (HDOH), and the Food and Drug
      Administration (FDA), as based on invalid QMC conclusions, clarifying now also
      basic facts and facilitating constructive discussions. 

PMID- 27043545
TI  - Novel Insights into the Role of Long Noncoding RNA in Ocular Diseases.
AB  - Recent advances have suggested that long noncoding RNAs (lncRNAs) are
      differentially expressed in ocular tissues and play a critical role in the
      pathogenesis of different types of eye diseases. Here, we summarize the functions
      and mechanisms of known aberrantly-expressed lncRNAs and present a brief overview
      of relevant reports about lncRNAs in such ocular diseases as glaucoma,
      proliferative vitreoretinopathy (PVR), diabeticretinopathy (DR), and ocular
      tumors. We intend to highlight comprehensive studies that provide detailed data
      about the mechanisms of lncRNAs, their applications as diagnostic or prognostic
      biomarkers, and their potential therapeutic targets. Although our understanding
      of lncRNAs is still in its infancy, these examples may provide helpful insights
      into the methods by which lncRNAs interfere with ocular diseases. 

PMID- 27043546
TI  - Gastrointestinal Endogenous Protein-Derived Bioactive Peptides: An in Vitro Study
      of Their Gut Modulatory Potential.
AB  - A recently proposed paradigm suggests that, like their dietary counterparts,
      digestion of gastrointestinal endogenous proteins (GEP) may also produce
      bioactive peptides. With an aim to test this hypothesis, in vitro digests of four
      GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a
      dietary protein chicken albumin (CA) were screened for their angiotensin-I
      converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH)
      and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential
      following simulated in vitro gastrointestinal digestion. Further, the resultant
      small intestinal digests were enriched to obtain peptides between 3-10 kDa in
      size. All in vitro digests of the four GEP were found to inhibit ACE-I compared
      to the positive control captopril when assayed at a concentration of 1 mg/mL,
      while the LYS < 3-kDa permeate fraction inhibited renin by 40% (+/-1.79%). The
      LYS < 10-kDa fraction inhibited PAF-AH by 39% (+/-4.34%), and the SA < 3-kDa
      fraction inhibited DPP-IV by 45% (+/-1.24%). The MUC < 3-kDa fraction had an ABTS
      inhibition antioxidant activity of 150 (+/-24.79) uM trolox equivalent and the
      LYS < 10-kDa fraction inhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) by 54% (+/
      1.62%). Moreover, over 190 peptide-sequences were identified from the bioactive
      GEP fractions. The findings of the present study indicate that GEP are a
      significant source of bioactive peptides which may influence gut function. 

PMID- 27043547
TI  - KRAS G12V Mutation Detection by Droplet Digital PCR in Circulating Cell-Free DNA
      of Colorectal Cancer Patients.
AB  - KRAS mutations are responsible for resistance to anti-epidermal growth factor
      receptor (EGFR) therapy in colorectal cancer patients. These mutations sometimes
      appear once treatment has started. Detection of KRAS mutations in circulating
      cell-free DNA in plasma ("liquid biopsy") by droplet digital PCR (ddPCR) has
      emerged as a very sensitive and promising alternative to serial biopsies for
      disease monitoring. In this study, KRAS G12V mutation was analyzed by ddPCR in
      plasma DNA from 10 colorectal cancer patients and compared to six healthy donors.
      The percentage of KRAS G12V mutation relative to wild-type sequences in tumor
      derived DNA was also determined. KRAS G12V mutation circulating in plasma was
      detected in 9 of 10 colorectal cancer patients whose tumors were also mutated.
      Colorectal cancer patients had 35.62 copies of mutated KRAS/mL plasma, whereas in
      healthy controls only residual copies were found (0.62 copies/mL, p = 0.0066).
      Interestingly, patients with metastatic disease showed a significantly higher
      number of mutant copies than M0 patients (126.25 versus 9.37 copies/mL, p =
      0.0286). Wild-type KRAS was also significantly elevated in colorectal cancer
      patients compared to healthy controls (7718.8 versus 481.25 copies/mL, p =
      0.0002). In conclusion, KRAS G12V mutation is detectable in plasma of colorectal
      cancer patients by ddPCR and could be used as a non-invasive biomarker. 

PMID- 27043548
TI  - Mesenchymal Stem Cells Ameliorated Glucolipotoxicity in HUVECs through TSG-6.
AB  - Glucolipotoxicity is one of the critical causal factors of diabetic
      complications. Whether mesenchymal stem cells (MSCs) have effects on
      glucolipotoxicity in human umbilical vein endothelial cells (HUVECs) and
      mechanisms involved are unclear. Thirty mM glucose plus 100 MUM palmitic acid was
      used to induce glucolipotoxicity in HUVECs. MSCs and HUVECs were co-cultured at
      the ratio of 1:5 via Transwell system. The mRNA expressions of inflammatory
      factors were detected by RT-qPCR. The productions of reactive oxygen species
      (ROS), cell cycle and apoptosis were analyzed by flow cytometry. The tumor
      necrosis factor-alpha stimulated protein 6 (TSG-6) was knockdown in MSCs by RNA
      interference. High glucose and palmitic acid remarkably impaired cell viability
      and tube formation capacity, as well as increased the mRNA expression of
      inflammatory factors, ROS levels, and cell apoptosis in HUVECs. MSC co
      cultivation ameliorated these detrimental effects in HUVECs, but no effect on ROS
      production. Moreover, TSG-6 was dramatically up-regulated by high glucose and
      fatty acid stimulation in both MSCs and HUVECs. TSG-6 knockdown partially
      abolished the protection mediated by MSCs. MSCs had protective effects on high
      glucose and palmitic acid induced glucolipotoxicity in HUVECs, and TSG-6 secreted
      by MSCs was likely to play an important role in this process. 

PMID- 27043549
TI  - Do Variants in GSTs Modify the Association between Traffic Air Pollution and
      Asthma in Adolescence?
AB  - Polymorphisms in genes involved in the oxidative stress response may partially
      explain the documented heterogeneous associations between traffic-related air
      pollution (TRAP) exposure and asthma and allergies in children. We investigated
      whether the GSTT1, GSTM1 and GSTP1 gene polymorphisms modified the associations
      between TRAP exposure during the first year of life and asthma, wheeze and hay
      fever in adolescence. We used a birth cohort of 620 high risk infants from the
      Melbourne Atopy Cohort Study. TRAP exposure during the first year of life was
      defined as the cumulative length of major roads within 150 m of each
      participant's residence during the first year of life. Wheeze, asthma and hay
      fever were measured at ages 12 (n = 370) and 18 (n = 434) years. The associations
      and interactions with glutathione S-transferases (GST s) were investigated using
      regression models. Overall, there was no relationship between TRAP exposure
      during the first year of life and current asthma, wheeze and hay fever at ages 12
      or 18 years. However, in GSTT1 null carriers, every 100 m increase in cumulative
      lengths of major road exposure during the first year of life was associated with
      a 2.31-fold increased risk of wheeze and a 2.15-fold increased risk of asthma at
      12 years. TRAP is associated with some respiratory outcomes in carriers of
      genetic polymorphisms in oxidative stress metabolism genes. 

PMID- 27043551
TI  - The Impact of Specific Viruses on Clinical Outcome in Children Presenting with
      Acute Heart Failure.
AB  - The presence and type of viral genomes have been suggested as the main etiology
      for inflammatory dilated cardiomyopathy. Information on the clinical implication
      of this finding in a large population of children is lacking. We evaluated the
      prevalence, type, and clinical impact of specific viral genomes in endomyocardial
      biopsies (EMB) collected between 2001 and 2013 among 63 children admitted to our
      hospital for acute heart failure (median age 2.8 years). Viral genome was
      searched by polymerase chain reaction (PCR). Patients underwent a complete two
      dimensional echocardiographic examination at hospital admission and at discharge
      and were followed-up for 10 years. Twenty-seven adverse events (7 deaths and 20
      cardiac transplantations) occurred during the follow-up. Viral genome was
      amplified in 19/63 biopsies (35%); PVB19 was the most commonly isolated virus.
      Presence of specific viral genome was associated with a significant recovery in
      ejection fraction, compared to patients without viral evidence (p < 0.05). In Cox
      regression analysis, higher survival rate was related to virus-positive biopsies
      (p < 0.05). When comparing long-term prognosis among different viral groups, a
      trend towards better prognosis was observed in the presence of isolated
      Parvovirus B19 (PVB19) (p = 0.07). In our series, presence of a virus-positive
      EMB (mainly PVB19) was associated with improvement over time in cardiac function
      and better long-term prognosis. 

PMID- 27043550
TI  - Diet, Microbiota, Obesity, and NAFLD: A Dangerous Quartet.
AB  - Recently, the importance of the gut-liver-adipose tissue axis has become evident.
      Nonalcoholic fatty liver disease (NAFLD) is the hepatic disease of a systemic
      metabolic disorder that radiates from energy-surplus induced adiposopathy. The
      gut microbiota has tremendous influences in our whole-body metabolism, and is
      crucial for our well-being and health. Microorganisms precede humans in more than
      400 million years and our guest flora evolved with us in order to help us face
      aggressor microorganisms, to help us maximize the energy that can be extracted
      from nutrients, and to produce essential nutrients/vitamins that we are not
      equipped to produce. However, our gut microbiota can be disturbed, dysbiota, and
      become itself a source of stress and injury. Dysbiota may adversely impact
      metabolism and immune responses favoring obesity and obesity-related disorders
      such as insulin resistance/diabetes mellitus and NAFLD. In this review, we will
      summarize the latest evidence of the role of microbiota/dysbiota in diet-induced
      obesity and NAFLD, as well as the potential therapeutic role of targeting the
      microbiota in this set. 

PMID- 27043552
TI  - High Salt Diet Affects Renal Sodium Excretion and ERRalpha Expression.
AB  - Kidneys regulate the balance of water and sodium and therefore are related to
      blood pressure. It is unclear whether estrogen-related receptor alpha (ERRalpha),
      an orphan nuclear receptor and transcription factor highly expressed in kidneys,
      affects the reabsorption of water and sodium. The aim of this study was to
      determine whether changes in the expressions of ERRalpha, Na+/K+-ATPase and
      epithelial sodium channel (ENaC) proteins affected the reabsorption of water and
      sodium in kidneys of Dahl salt-sensitive (DS) rats. SS.13BN rats, 98% homologous
      to the DS rats, were used as a normotensive control group. The 24 h urinary
      sodium excretion of the DS and SS.13BN rats increased after the 6-week high salt
      diet intervention, while sodium excretion was increased in DS rats with daidzein
      (agonist of ERRalpha) treatment. ERRalpha expression was decreased, while beta-
      and gamma-ENaC mRNA expressions were increased upon high sodium diet treatment in
      the DS rats. In the chromatin immunoprecipitation (CHIP) assay, positive PCR
      signals were obtained in samples treated with anti-ERRalpha antibody. The
      transcriptional activity of ERRalpha was decreased upon high salt diet
      intervention. ERRalpha reduced the expressions of beta- and gamma-ENaC by binding
      to the ENaC promoter, thereby increased Na+ reabsorption. Therefore, ERRalpha
      might be one of the factors causing salt-sensitive hypertension. 

PMID- 27043553
TI  - Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal
      Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry
      Study.
AB  - We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain
      atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect
      regional brain changes when comparing 2 time points on high resolution T1
      weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92
      relapsing-remitting MS patients obtained 12 months apart were analysed with VGM.
      New lesions and volume changes of focal MS lesions as well as in the surrounding
      tissue were identified by visual inspection on colour coded VGM maps. Lesions
      were dichotomized in active and inactive lesions. Active lesions, defined by
      either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions
      (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking
      lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were
      accompanied by tissue shrinkage in surrounding and/or functionally related
      regions. Volume loss within the corpus callosum was highly correlated with the
      number of lesions in its close proximity. Volume loss in the lateral geniculate
      nucleus was correlated with lesions along the optic radiation. VGM analysis
      provides strong evidence that all active lesion types (NL, CEL, and CSL)
      contribute to brain volume reduction in the vicinity of lesions and/or in
      anatomically and functionally related areas of the brain. 

PMID- 27043554
TI  - RORC2 Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis.
AB  - BACKGROUND: In the present study, we aimed to evaluate whether polymorphisms
      within the RORc2 gene are involved in the risk and severity of rheumatoid
      arthritis (RA). METHODS: 591 RA patients and 341 healthy individuals were
      examined for RORc2 gene polymorphisms. Serum retinoic acid receptor-related
      orphan receptor C (RORc) levels were measured by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: The rs9826 A/G, rs12045886 T/C and rs9017 G/A RORc2 gene
      SNPs show no significant differences in the proportion of cases and control.
      Overall, rs9826 and rs9017 were in high linkage disequilibrium (LD) with D' =
      0.952 and r2 = 0.874, except rs9826 and rs12045886; and rs12045886 and rs9017 in
      weak LD. The genotype-phenotype analysis showed a significant association between
      RORc2 rs9826 A/G and rs9017 G/A single nucleotide polymorphisms (SNPs) and median
      of C-reactive protein (CRP). Serum RORc levels was higher in RA patients with
      rs9826AA, rs12045886TT and -TC, and rs9017AA genotypes compared to healthy
      subjects with the same genotypes (p = 0.02, p = 0.04 and p = 0.01, respectively).
      Moreover, the median of RORc protein level was higher in RA patients with number
      of swollen joints bigger then 3 (p = 0.04) and with Health Assessment
      Questionnaires (HAQ) score bigger then 1.5 (0.049). CONCLUSIONS: Current findings
      indicated that the RORc2 genetic polymorphism and the RORc2 protein level may be
      associated with severity of RA in the Polish population.

PMID- 27043555
TI  - Diagnosing Lung Cancers through Examination of Micro-RNA Biomarkers in Blood,
      Plasma, Serum and Sputum: A Review and Summary of Current Literature.
AB  - Lung cancer is the leading cause of cancer related morbidity and mortality
      worldwide. Currently, the vast majority of lung cancers are diagnosed at a late
      stage, when patients become symptomatic leading to dismal, less than 15% five
      year survival rates. Evidence has demonstrated that screening computed tomography
      scans can be used to detect lung cancer, but these scans have high false positive
      rates. Therefore, there is a continued need for the development of minimally
      invasive methods to screen the high risk population and diagnose lung cancer at
      an earlier, curable stage. One such promising area is the use micro-RNAs. These
      are short, non-coding RNA molecules that have been shown in previous research to
      be dysregulated in cancers. This review will focus on the potential use of miRNA
      levels in various biological fluids (whole blood, plasma, serum, and sputum) and
      demonstrate their potential utility as screening and diagnostic biomarkers for
      lung cancer. Current research will be analyzed and compared, and future
      directions in establishing the use of miRNAs for detecting lung cancer will be
      discussed. 

PMID- 27043556
TI  - Optical Absorption Spectra and Electronic Properties of Symmetric and Asymmetric
      Squaraine Dyes for Use in DSSC Solar Cells: DFT and TD-DFT Studies.
AB  - The electronic absorption spectra, ground-state geometries and electronic
      structures of symmetric and asymmetric squaraine dyes (SQD1-SQD4) were
      investigated using density functional theory (DFT) and time-dependent (TD-DFT)
      density functional theory at the B3LYP/6-311++G** level. The calculated ground
      state geometries reveal pronounced conjugation in these dyes. Long-range
      corrected time dependent density functionals Perdew, Burke and Ernzerhof (PBE,
      PBE1PBE (PBE0)), and the exchange functional of Tao, Perdew, Staroverov, and
      Scuseria (TPSSh) with 6-311++G** basis set were employed to examine optical
      absorption properties. In an extensive comparison between the optical data and
      DFT benchmark calculations, the BEP functional with 6-311++G** basis set was
      found to be the most appropriate in describing the electronic absorption spectra.
      The calculated energy values of lowest unoccupied molecular orbitals (LUMO) were
      3.41, 3.19, 3.38 and 3.23 eV for SQD1, SQD2, SQD3, and SQD4, respectively. These
      values lie above the LUMO energy (-4.26 eV) of the conduction band of TiO2
      nanoparticles indicating possible electron injection from the excited dyes to the
      conduction band of the TiO2 in dye-sensitized solar cells (DSSCs). Also,
      aromaticity computation for these dyes are in good agreement with the data
      obtained optically and geometrically with SQD4 as the highest aromatic structure.
      Based on the optimized molecular geometries, relative positions of the frontier
      orbitals, and the absorption maxima, we propose that these dyes are suitable
      components of photovoltaic DSSC devices. 

PMID- 27043558
TI  - Characterization of Virulence Properties of Aeromonas veronii Isolated from
      Diseased Gibel Carp (Carassius gibelio).
AB  - Aeromonas veronii is a kind of opportunistic pathogen to fish and humans,
      significantly impending aquaculture production. Recently, we isolated two A.
      veronii strains, named GYC1 and GYC2, from diseased Gibel carp (Carassius
      gibelio) in China. Based on gyrB (DNA gyrase B subunit) genes of GYC1 and GYC2,
      the constructed phylogenetic tree showed that the two strains were clustered with
      A. veronii. Sixteen virulence genes related to the pathogenicity of Aeromonas
      spp. were subjected to PCR assay. The genes of ompAI, ompAII, lafA, act, aer,
      fla, gcaT and acg were detected in the two strains, while genes of hly, ahp, lip,
      ast and alt were not detected. Additionally, genes eprCAI, ela and exu were only
      detected in the strain GYC1. Furthermore, the results of extracellular enzyme
      analysis revealed that the two isolates can produce hemolysin, caseinase,
      esterase, amylase and lecithinase, which were closely related to the
      pathogenicity of the two strains. However, the results showed that there was no
      gelatinase activity in either strain. According to the antibiotic resistant
      assay, the two strains were sensitive to cephalosporins and aminoglycosides,
      while they were resistant to penicillins and quinolones. Through this study, the
      virulence characteristics, including virulence genes and extracellular enzymes,
      the pathogenicity of A. veronii was clarified, enhancing the understanding about
      this pathogenic bacterium and providing the theoretical basis in disease control.

PMID- 27043559
TI  - An Energy Aware Adaptive Sampling Algorithm for Energy Harvesting WSN with Energy
      Hungry Sensors.
AB  - Wireless sensor nodes have a limited power budget, though they are often expected
      to be functional in the field once deployed for extended periods of time.
      Therefore, minimization of energy consumption and energy harvesting technology in
      Wireless Sensor Networks (WSN) are key tools for maximizing network lifetime, and
      achieving self-sustainability. This paper proposes an energy aware Adaptive
      Sampling Algorithm (ASA) for WSN with power hungry sensors and harvesting
      capabilities, an energy management technique that can be implemented on any WSN
      platform with enough processing power to execute the proposed algorithm. An
      existing state-of-the-art ASA developed for wireless sensor networks with power
      hungry sensors is optimized and enhanced to adapt the sampling frequency
      according to the available energy of the node. The proposed algorithm is
      evaluated using two in-field testbeds that are supplied by two different energy
      harvesting sources (solar and wind). Simulation and comparison between the state
      of-the-art ASA and the proposed energy aware ASA (EASA) in terms of energy
      durability are carried out using in-field measured harvested energy (using both
      wind and solar sources) and power hungry sensors (ultrasonic wind sensor and gas
      sensors). The simulation results demonstrate that using ASA in combination with
      an energy aware function on the nodes can drastically increase the lifetime of a
      WSN node and enable self-sustainability. In fact, the proposed EASA in
      conjunction with energy harvesting capability can lead towards perpetual WSN
      operation and significantly outperform the state-of-the-art ASA. 

PMID- 27043557
TI  - Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a
      Largely Reduced Affinity for the Target Antigen.
AB  - PEGylation of biomolecules is a major approach to increase blood stream half
      life, stability and solubility of biotherapeutics and to reduce their
      immunogenicity, aggregation potential and unspecific interactions with other
      proteins and tissues. Antibodies have generally long half-lives due to high
      molecular mass and stability toward proteases, however their size lowers to some
      extent their potential because of a reduced ability to penetrate tissues,
      especially those of tumor origin. Fab or otherwise engineered smaller fragments
      are an alternative but are less stable and are much less well retained in
      circulation. We have here investigated the effects of various PEGylations on the
      binding properties and in vivo half-life of Fab fragments derived from the
      enzymatic splitting of Trastuzumab. We find that PEGylation increases the half
      life of the molecules but also strongly affects the ability to recognize the
      target antigen in a way that is dependent on the extent and position of the
      chemical modification. Data thus support the concept that polyethylene glycol
      (PEG) conjugation on Trastuzumab Fabs increases half-life but reduces their
      affinity and this is a fine balance, which must be carefully considered for the
      design of strategies based on the use of antibody fragments. 

PMID- 27043560
TI  - Performance Improvement of Total Ionization Dose Radiation Sensor Devices Using
      Fluorine-Treated MOHOS.
AB  - Fluorine-treated titanium nitride-silicon oxide-hafnium oxide-silicon oxide
      silicon devices (hereafter F-MOHOS) are candidates for total ionization dose
      (TID) radiation sensor applications. The main subject of the study reportedherein
      is the performance improvement in terms of TID radiation-induced charge
      generation effect and charge-retention reliability characterization for F-MOHOS
      devices. In the case of F-MOHOS TID radiation sensors, the gamma radiation
      induces a significant decrease of threshold voltage VT and the radiation-induced
      charge density is nearly six times larger than that of standard metal-oxide
      nitride-oxide-silicon MONOS devices. The decrease of VT for F-MOHOS after gamma
      irradiation has a strong correlation to the TID up to 5 Mrad gamma irradiation as
      well. The improvement of charge retention loss for F-MOHOS devices is nearly 15%
      better than that of metal-oxide-hafnium oxide-oxide-silicon MOHOS devices. The F
      MOHOS device described in this study demonstrates better feasibility for non
      volatile TID radiation sensing in the future. 

PMID- 27043561
TI  - Non-Invasive Examination of Plant Surfaces by Opto-Electronic Means--Using Russet
      as a Prime Example.
AB  - (1) BACKGROUND: Many disorders and diseases of agricultural produce change the
      physical features of surfaces of plant organs; in terms of russet, e.g., of apple
      or pear, affected fruit peel becomes rough and brown in color, which is
      associated with changes in light reflection; (2) OBJECTIVE AND METHODS: The
      objective of the present project was an interdisciplinary approach between
      horticultural science and engineering to examine two new innovative technologies
      as to their suitability for the non-destructive determination of surfaces of
      plant organs, using russet as an example, and (a) an industrial luster sensor
      (type CZ-H72, Keyence, Japan) and (b) a new type of a three-dimensional (3D)
      color microscope (VHX 5000); (3) RESULTS: In the case of russet, i.e.,
      suberinization of the fruit peel, peel roughness increased by ca. 2.5-fold from
      ca. 20 um to ca. 50 um on affected fruit sections when viewed at 200*
      magnification. Russeted peel showed significantly reduced luster, with smaller
      variation than russet-devoid peel with larger variation; (4) CONCLUSION: These
      results indicate that both sensors are suitable for biological material and their
      use for non-contact, non-invasive detection of surface disorders on agricultural
      produce such as russet may be a very powerful tool for many applications in
      agriculture and beyond in the future. 

PMID- 27043562
TI  - Tracking Mobile Sinks via Analysis of Movement Angle Changes in WSNs.
AB  - Existing methods for tracking mobile sinks in Wireless Sensor Networks (WSNs)
      often incur considerable energy consumption and overhead. To address this issue,
      we propose a Detour-Aware Mobile Sink Tracking (DAMST) method via analysis of
      movement angle changes of mobile sinks, for collecting data in a low-overhead and
      energy efficient way. In the proposed method, while a mobile sink passes through
      a region, it appoints a specific node as a region agent to collect information of
      the whole region, and records nodes near or on its trajectory as footprints. If
      it needs information from the region agent in a future time it will construct an
      energy efficient path from the region agent to itself by calculating its own
      movement angles according to the footprints, as well as getting rid of detours by
      analyzing these movement angles. Finally, the performance of the tracking method
      is evaluated systematically under different trajectory patterns and footprint
      appointment intervals. The simulation results consolidate that DAMST has
      advantages in reducing energy consumption and data overhead. 

PMID- 27043563
TI  - Geometry-Based Distributed Spatial Skyline Queries in Wireless Sensor Networks.
AB  - Algorithms for skyline querying based on wireless sensor networks (WSNs) have
      been widely used in the field of environmental monitoring. Because of the multi
      dimensional nature of the problem of monitoring spatial position, traditional
      skyline query strategies cause enormous computational costs and energy
      consumption. To ensure the efficient use of sensor energy, a geometry-based
      distributed spatial query strategy (GDSSky) is proposed in this paper. Firstly,
      the paper presents a geometry-based region partition strategy. It uses the
      skyline area reduction method based on the convex hull vertices, to quickly query
      the spatial skyline data related to a specific query area, and proposes a
      regional partition strategy based on the triangulation method, to implement
      distributed queries in each sub-region and reduce the comparison times between
      nodes. Secondly, a sub-region clustering strategy is designed to group the data
      inside into clusters for parallel queries that can save time. Finally, the paper
      presents a distributed query strategy based on the data node tree to traverse all
      adjacent sensors' monitoring locations. It conducts spatial skyline queries for
      spatial skyline data that have been obtained and not found respectively, so as to
      realize the parallel queries. A large number of simulation results shows that
      GDSSky can quickly return the places which are nearer to query locations and have
      larger pollution capacity, and significantly reduce the WSN energy consumption. 

PMID- 27043564
TI  - Human Detection Based on the Generation of a Background Image and Fuzzy System by
      Using a Thermal Camera.
AB  - Recently, human detection has been used in various applications. Although visible
      light cameras are usually employed for this purpose, human detection based on
      visible light cameras has limitations due to darkness, shadows, sunlight, etc. An
      approach using a thermal (far infrared light) camera has been studied as an
      alternative for human detection, however, the performance of human detection by
      thermal cameras is degraded in case of low temperature differences between humans
      and background. To overcome these drawbacks, we propose a new method for human
      detection by using thermal camera images. The main contribution of our research
      is that the thresholds for creating the binarized difference image between the
      input and background (reference) images can be adaptively determined based on
      fuzzy systems by using the information derived from the background image and
      difference values between background and input image. By using our method, human
      area can be correctly detected irrespective of the various conditions of input
      and background (reference) images. For the performance evaluation of the proposed
      method, experiments were performed with the 15 datasets captured under different
      weather and light conditions. In addition, the experiments with an open database
      were also performed. The experimental results confirm that the proposed method
      can robustly detect human shapes in various environments. 

PMID- 27043565
TI  - On the Achievable Throughput Over TVWS Sensor Networks.
AB  - In this letter, we study the throughput achievable by an unlicensed sensor
      network operating over TV white space spectrum in presence of coexistence
      interference. Through the letter, we first analytically derive the achievable
      throughput as a function of the channel ordering. Then, we show that the problem
      of deriving the maximum expected throughput through exhaustive search is
      computationally unfeasible. Finally, we derive a computational-efficient
      algorithm characterized by polynomial-time complexity to compute the channel set
      maximizing the expected throughput and, stemming from this, we derive a closed
      form expression of the maximum expected throughput. Numerical simulations
      validate the theoretical analysis. 

PMID- 27043566
TI  - A Trust-Based Adaptive Probability Marking and Storage Traceback Scheme for WSNs.
AB  - Security is a pivotal issue for wireless sensor networks (WSNs), which are
      emerging as a promising platform that enables a wide range of military,
      scientific, industrial and commercial applications. Traceback, a key cyber
      forensics technology, can play an important role in tracing and locating a
      malicious source to guarantee cybersecurity. In this work a trust-based adaptive
      probability marking and storage (TAPMS) traceback scheme is proposed to enhance
      security for WSNs. In a TAPMS scheme, the marking probability is adaptively
      adjusted according to the security requirements of the network and can
      substantially reduce the number of marking tuples and improve network lifetime.
      More importantly, a high trust node is selected to store marking tuples, which
      can avoid the problem of marking information being lost. Experimental results
      show that the total number of marking tuples can be reduced in a TAPMS scheme,
      thus improving network lifetime. At the same time, since the marking tuples are
      stored in high trust nodes, storage reliability can be guaranteed, and the
      traceback time can be reduced by more than 80%. 

PMID- 27043567
TI  - Optical Riblet Sensor: Beam Parameter Requirements for the Probing Laser Source.
AB  - Beam parameters of a probing laser source in an optical riblet sensor are studied
      by considering the high demands on a sensors' precision and reliability for the
      determination of deviations of the geometrical shape of a riblet. Mandatory
      requirements, such as minimum intensity and light polarization, are obtained by
      means of detailed inspection of the optical response of the riblet using ray and
      wave optics; the impact of wavelength is studied. Novel measures for analyzing
      the riblet shape without the necessity of a measurement with a reference sample
      are derived; reference values for an ideal riblet structure obtained with the
      optical riblet sensor are given. The application of a low-cost, frequency-doubled
      Nd:YVO4 laser pointer sufficient to serve as a reliable laser source in an
      appropriate optical riblet sensor is discussed. 

PMID- 27043568
TI  - Dynamic RACH Partition for Massive Access of Differentiated M2M Services.
AB  - In machine-to-machine (M2M) networks, a key challenge is to overcome the overload
      problem caused by random access requests from massive machine-type communication
      (MTC) devices. When differentiated services coexist, such as delay-sensitive and
      delay-tolerant services, the problem becomes more complicated and challenging.
      This is because delay-sensitive services often use more aggressive policies, and
      thus, delay-tolerant services get much fewer chances to access the network. To
      conquer the problem, we propose an efficient mechanism for massive access control
      over differentiated M2M services, including delay-sensitive and delay-tolerant
      services. Specifically, based on the traffic loads of the two types of services,
      the proposed scheme dynamically partitions and allocates the random access
      channel (RACH) resource to each type of services. The RACH partition strategy is
      thoroughly optimized to increase the access performances of M2M networks.
      Analyses and simulation demonstrate the effectiveness of our design. The proposed
      scheme can outperform the baseline access class barring (ACB) scheme, which
      ignores service types in access control, in terms of access success probability
      and the average access delay. 

PMID- 27043569
TI  - Single-Photon Avalanche Diode with Enhanced NIR-Sensitivity for Automotive LIDAR
      Systems.
AB  - A single-photon avalanche diode (SPAD) with enhanced near-infrared (NIR)
      sensitivity has been developed, based on 0.18 MUm CMOS technology, for use in
      future automotive light detection and ranging (LIDAR) systems. The newly proposed
      SPAD operating in Geiger mode achieves a high NIR photon detection efficiency
      (PDE) without compromising the fill factor (FF) and a low breakdown voltage of
      approximately 20.5 V. These properties are obtained by employing two custom
      layers that are designed to provide a full-depletion layer with a high electric
      field profile. Experimental evaluation of the proposed SPAD reveals an FF of
      33.1% and a PDE of 19.4% at 870 nm, which is the laser wavelength of our LIDAR
      system. The dark count rate (DCR) measurements shows that DCR levels of the
      proposed SPAD have a small effect on the ranging performance, even if the worst
      DCR (12.7 kcps) SPAD among the test samples is used. Furthermore, with an eye
      toward vehicle installations, the DCR is measured over a wide temperature range
      of 25-132  degrees C. The ranging experiment demonstrates that target distances
      are successfully measured in the distance range of 50-180 cm. 

PMID- 27043570
TI  - Background Subtraction Based on Three-Dimensional Discrete Wavelet Transform.
AB  - Background subtraction without a separate training phase has become a critical
      task, because a sufficiently long and clean training sequence is usually
      unavailable, and people generally thirst for immediate detection results from the
      first frame of a video. Without a training phase, we propose a background
      subtraction method based on three-dimensional (3D) discrete wavelet transform
      (DWT). Static backgrounds with few variations along the time axis are
      characterized by intensity temporal consistency in the 3D space-time domain and,
      hence, correspond to low-frequency components in the 3D frequency domain.
      Enlightened by this, we eliminate low-frequency components that correspond to
      static backgrounds using the 3D DWT in order to extract moving objects. Owing to
      the multiscale analysis property of the 3D DWT, the elimination of low-frequency
      components in sub-bands of the 3D DWT is equivalent to performing a pyramidal 3D
      filter. This 3D filter brings advantages to our method in reserving the inner
      parts of detected objects and reducing the ringing around object boundaries.
      Moreover, we make use of wavelet shrinkage to remove disturbance of intensity
      temporal consistency and introduce an adaptive threshold based on the entropy of
      the histogram to obtain optimal detection results. Experimental results show that
      our method works effectively in situations lacking training opportunities and
      outperforms several popular techniques. 

PMID- 27043571
TI  - Multichannel-Sensing Scheduling and Transmission-Energy Optimizing in Cognitive
      Radio Networks with Energy Harvesting.
AB  - This paper considers cognitive radio networks (CRNs) utilizing multiple time
      slotted primary channels in which cognitive users (CUs) are powered by energy
      harvesters. The CUs are under the consideration that hardware constraints on
      radio devices only allow them to sense and transmit on one channel at a time. For
      a scenario where the arrival of harvested energy packets and the battery capacity
      are finite, we propose a scheme to optimize (i) the channel-sensing schedule
      (consisting of finding the optimal action (silent or active) and sensing order of
      channels) and (ii) the optimal transmission energy set corresponding to the
      channels in the sensing order for the operation of the CU in order to maximize
      the expected throughput of the CRN over multiple time slots. Frequency-switching
      delay, energy-switching cost, correlation in spectrum occupancy across time and
      frequency and errors in spectrum sensing are also considered in this work. The
      performance of the proposed scheme is evaluated via simulation. The simulation
      results show that the throughput of the proposed scheme is greatly improved, in
      comparison to related schemes in the literature. The collision ratio on the
      primary channels is also investigated. 

PMID- 27043572
TI  - Cost-Effective Encryption-Based Autonomous Routing Protocol for Efficient and
      Secure Wireless Sensor Networks.
AB  - The deployment of intelligent remote surveillance systems depends on wireless
      sensor networks (WSNs) composed of various miniature resource-constrained
      wireless sensor nodes. The development of routing protocols for WSNs is a major
      challenge because of their severe resource constraints, ad hoc topology and
      dynamic nature. Among those proposed routing protocols, the biology-inspired self
      organized secure autonomous routing protocol (BIOSARP) involves an artificial
      immune system (AIS) that requires a certain amount of time to build up knowledge
      of neighboring nodes. The AIS algorithm uses this knowledge to distinguish
      between self and non-self neighboring nodes. The knowledge-building phase is a
      critical period in the WSN lifespan and requires active security measures. This
      paper proposes an enhanced BIOSARP (E-BIOSARP) that incorporates a random key
      encryption mechanism in a cost-effective manner to provide active security
      measures in WSNs. A detailed description of E-BIOSARP is presented, followed by
      an extensive security and performance analysis to demonstrate its efficiency. A
      scenario with E-BIOSARP is implemented in network simulator 2 (ns-2) and is
      populated with malicious nodes for analysis. Furthermore, E-BIOSARP is compared
      with state-of-the-art secure routing protocols in terms of processing time,
      delivery ratio, energy consumption, and packet overhead. The findings show that
      the proposed mechanism can efficiently protect WSNs from selective forwarding,
      brute-force or exhaustive key search, spoofing, eavesdropping, replaying or
      altering of routing information, cloning, acknowledgment spoofing, HELLO flood
      attacks, and Sybil attacks. 

PMID- 27043573
TI  - SACRB-MAC: A High-Capacity MAC Protocol for Cognitive Radio Sensor Networks in
      Smart Grid.
AB  - The Cognitive Radio Sensor Network (CRSN) is considered as a viable solution to
      enhance various aspects of the electric power grid and to realize a smart grid.
      However, several challenges for CRSNs are generated due to the harsh wireless
      environment in a smart grid. As a result, throughput and reliability become
      critical issues. On the other hand, the spectrum aggregation technique is
      expected to play an important role in CRSNs in a smart grid. By using spectrum
      aggregation, the throughput of CRSNs can be improved efficiently, so as to
      address the unique challenges of CRSNs in a smart grid. In this regard, we
      proposed Spectrum Aggregation Cognitive Receiver-Based MAC (SACRB-MAC), which
      employs the spectrum aggregation technique to improve the throughput performance
      of CRSNs in a smart grid. Moreover, SACRB-MAC is a receiver-based MAC protocol,
      which can provide a good reliability performance. Analytical and simulation
      results demonstrate that SACRB-MAC is a promising solution for CRSNs in a smart
      grid. 

PMID- 27043574
TI  - An Adaptive Data Gathering Scheme for Multi-Hop Wireless Sensor Networks Based on
      Compressed Sensing and Network Coding.
AB  - Joint design of compressed sensing (CS) and network coding (NC) has been
      demonstrated to provide a new data gathering paradigm for multi-hop wireless
      sensor networks (WSNs). By exploiting the correlation of the network sensed data,
      a variety of data gathering schemes based on NC and CS (Compressed Data Gathering
      -CDG) have been proposed. However, these schemes assume that the sparsity of the
      network sensed data is constant and the value of the sparsity is known before
      starting each data gathering epoch, thus they ignore the variation of the data
      observed by the WSNs which are deployed in practical circumstances. In this
      paper, we present a complete design of the feedback CDG scheme where the sink
      node adaptively queries those interested nodes to acquire an appropriate number
      of measurements. The adaptive measurement-formation procedure and its termination
      rules are proposed and analyzed in detail. Moreover, in order to minimize the
      number of overall transmissions in the formation procedure of each measurement,
      we have developed a NP-complete model (Maximum Leaf Nodes Minimum Steiner Nodes-
      MLMS) and realized a scalable greedy algorithm to solve the problem. Experimental
      results show that the proposed measurement-formation method outperforms previous
      schemes, and experiments on both datasets from ocean temperature and practical
      network deployment also prove the effectiveness of our proposed feedback CDG
      scheme.

PMID- 27043575
TI  - Reverse-Bumpy-Ball-Type-Nanoreactor-Loaded Nylon Membranes as Peroxidase-Mimic
      Membrane Reactors for a Colorimetric Assay for H2O2.
AB  - Herein we report for the first time fabrication of reverse bumpy ball (RBB)-type
      nanoreactor-based flexible peroxidase-mimic membrane reactors (MRs). The RBB-type
      nanoreactors with gold nanoparticles embedded in the inner walls of carbon shells
      were loaded on nylon membranes through a facile filtration approach. The as
      prepared flexible catalytic membrane was studied as a peroxidase-mimic MR. It was
      found that the obtained peroxidase-mimic MR could exhibit several advantages over
      natural enzymes, such as facile and good recyclability, long-term stability and
      easy storage. Moreover, the RBB NS-modified nylon MRs as a peroxidase mimic
      provide a useful colorimetric assay for H2O2. 

PMID- 27043576
TI  - Development and Evaluation of Algorithms for Breath Alcohol Screening.
AB  - Breath alcohol screening is important for traffic safety, access control and
      other areas of health promotion. A family of sensor devices useful for these
      purposes is being developed and evaluated. This paper is focusing on algorithms
      for the determination of breath alcohol concentration in diluted breath samples
      using carbon dioxide to compensate for the dilution. The examined algorithms make
      use of signal averaging, weighting and personalization to reduce estimation
      errors. Evaluation has been performed by using data from a previously conducted
      human study. It is concluded that these features in combination will
      significantly reduce the random error compared to the signal averaging algorithm
      taken alone. 

PMID- 27043577
TI  - Identification of a Large Pool of Microorganisms with an Array of Porphyrin Based
      Gas Sensors.
AB  - The association between volatile compounds (VCs) and microorganisms, as
      demonstrated by several studies, may offer the ground for a rapid identification
      of pathogens. To this regard, chemical sensors are a key enabling technology for
      the exploitation of this opportunity. In this study, we investigated the
      performance of an array of porphyrin-coated quartz microbalance gas sensors in
      the identification of a panel of 12 bacteria and fungi. The porphyrins were metal
      complexes and the free base of a functionalized tetraphenylporphyrin. Our results
      show that the sensor array distinguishes the VC patterns produced by
      microorganisms in vitro. Besides being individually identified, bacteria are also
      sorted into Gram-positive and Gram-negative. 

PMID- 27043578
TI  - TTEO (Things Talk to Each Other): Programming Smart Spaces Based on IoT Systems.
AB  - The Internet of Things allows things in the world to be connected to each other
      and enables them to automate daily tasks without human intervention, eventually
      building smart spaces. This article demonstrates a prototype service based on the
      Internet of Things, TTEO (Things Talk to Each Other). We present the full details
      on the system architecture and the software platforms for IoT servers and
      devices, called Mobius and &Cube, respectively, complying with the globally
      applicable IoT standards, oneM2M, a unique identification scheme for a huge
      number of IoT devices, and service scenarios with an intuitive smartphone app. We
      hope that our approach will help developers and lead users for IoT devices and
      application services to establish an emerging IoT ecosystem, just like the
      ecosystem for smartphones and mobile applications. 

PMID- 27043579
TI  - Potential of IMU Sensors in Performance Analysis of Professional Alpine Skiers.
AB  - In this paper, we present an analysis to identify a sensor location for an
      inertial measurement unit (IMU) on the body of a skier and propose the best
      location to capture turn motions for training. We also validate the manner in
      which the data from the IMU sensor on the proposed location can characterize ski
      turns and performance with a series of statistical analyses, including a
      comparison with data collected from foot pressure sensors. The goal of the study
      is to logically identify the ideal location on the skier's body to attach the IMU
      sensor and the best use of the data collected for the skier. The statistical
      analyses and the hierarchical clustering method indicate that the pelvis is the
      best location for attachment of an IMU, and numerical validation shows that the
      data collected from this location can effectively estimate the performance and
      characteristics of the skier. Moreover, placement of the sensor at this location
      does not distract the skier's motion, and the sensor can be easily attached and
      detached. The findings of this study can be used for the development of a
      wearable device for the routine training of professional skiers. 

PMID- 27043580
TI  - GNSS Precise Kinematic Positioning for Multiple Kinematic Stations Based on A
      Priori Distance Constraints.
AB  - When applying the Global Navigation Satellite System (GNSS) for precise kinematic
      positioning in airborne and shipborne gravimetry, multiple GNSS receiving
      equipment is often fixed mounted on the kinematic platform carrying the
      gravimetry instrumentation. Thus, the distances among these GNSS antennas are
      known and invariant. This information can be used to improve the accuracy and
      reliability of the state estimates. For this purpose, the known distances between
      the antennas are applied as a priori constraints within the state parameters
      adjustment. These constraints are introduced in such a way that their accuracy is
      taken into account. To test this approach, GNSS data of a Baltic Sea shipborne
      gravimetric campaign have been used. The results of our study show that an
      application of distance constraints improves the accuracy of the GNSS kinematic
      positioning, for example, by about 4 mm for the radial component. 

PMID- 27043581
TI  - Comparative Studies on the Characteristic Fatty Acid Profiles of Four Different
      Chinese Medicinal Sargassum Seaweeds by GC-MS and Chemometrics.
AB  - Sargassum seaweeds produce abundant biomass in China and have long been used as
      herbal medicine and food. Their characteristic fatty acid (FA) profiles and
      related potential function in promoting cardiovascular health (CVH) have not been
      systematically investigated. In this study, FA profiles of four medicinal
      Sargassum were characterized using GC-MS. Principal component analysis was used
      to discriminate the four medicinal Sargassum, and orthogonal projection to latent
      structures discriminant analysis was carried out between the two official species
      HAI ZAO and between the two folk medicine species HAI QIAN. In all of the algae
      investigated, the major SFA and MUFA were palmitic and stearic acid,
      respectively, while the major PUFAs were linoleic, arachidonic, and
      eicosapentaenoic acid. S. fusiforme and S. horneri had higher concentrations of
      PUFAs. With respect to CVH, all of the studied species, particularly S.
      fusiforme, exhibited satisfactory levels such as PUFA/SFA ratio and n-6/n-3
      ratio. Each species possesses a unique FA profile and is discriminated clearly.
      Potential key FA markers (between the two Chinese official species, and between
      the two folk species) are assessed. The study provides characteristic fatty acid
      profiles of four Chinese medicinal Sargassum and their related potential function
      in promoting CVH. 

PMID- 27043582
TI  - In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of
      Activating Transcription Factor 3 against Human Colorectal Cancer Cells.
AB  - Phlorofucofuroeckol A (PFF-A), one of the phlorotannins found in brown algae, has
      been reported to exert anti-cancer property. However, the molecular mechanism for
      the anti-cancer effect of PFF-A has not been known. Activating transcription
      factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal
      cancer. The present study was performed to investigate the molecular mechanism by
      which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer
      cells. PFF-A decreased cell viability through apoptosis of human colorectal
      cancer cells. PFF-A increased ATF3 expression through regulating transcriptional
      activity. The responsible cis-element for ATF3 transcriptional activation by PFF
      A was cAMP response element binding protein (CREB), located between positions 
      147 and -85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases
      (JNK), glycogen synthase kinase (GSK) 3beta, and IkappaB kinase (IKK)-alpha
      blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated
      the cleavage of poly (ADP-ribose) polymerase (PARP) by PFF-A, while ATF3
      overexpression increased PFF-A-mediated cleaved PARP. These results suggest that
      PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3
      mediated pathway in human colorectal cancer cells. 

PMID- 27043583
TI  - Influences of Fucoxanthin on Alveolar Bone Resorption in Induced Periodontitis in
      Rat Molars.
AB  - The aim of this study was to evaluate the effects of systemic fucoxanthin
      treatment on alveolar bone resorption in rats with periodontitis. Thirty rats
      were divided into control, experimental periodontitis (EP), and experimental
      periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature
      for four weeks. After removal of the ligature, the rats in the EP-FUCO group were
      treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28
      consecutive days. At the end of the study, all of the rats were euthanized and
      intracardiac blood and mandible tissue samples were obtained for biochemical,
      immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in
      a slight decrease in tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6 levels and a significant decrease in oxidative stress index. It was
      observed that fucoxanthin caused a significant reduction in receptor activator of
      nuclear factor kappa-beta ligand (RANKL) levels and a statistically non
      significant elevation in osteoprotegerin and bone-alkaline phosphatase levels.
      There were no significant differences in alveolar bone loss levels between the EP
      and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a
      limited reduction in alveolar bone resorption in rats with periodontitis. One of
      the mechanisms underlying the mentioned limited effect might be related to the
      ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated
      osteoclastogenesis. 

PMID- 27043584
TI  - Concurrent Phosphorus Recovery and Energy Generation in Mediator-Less Dual
      Chamber Microbial Fuel Cells: Mechanisms and Influencing Factors.
AB  - This study investigated the mechanism and key factors influencing concurrent
      phosphorus (P) recovery and energy generation in microbial fuel cells (MFC)
      during wastewater treatment. Using a mediator-less dual chamber microbial fuel
      cell operated for 120 days; P was shown to precipitate as struvite when ammonium
      and magnesium chloride solutions were added to the cathode chamber. Monitoring
      data for chemical oxygen demand (COD), pH, oxidation reduction potential (ORP)
      and aeration flow rate showed that a maximum 38% P recovery was achieved; and
      this corresponds to 1.5 g/L, pH > 8, -550 +/- 10 mV and 50 mL/min respectively,
      for COD, pH(cathode), ORP and cathode aeration flow rate. More importantly, COD
      and aeration flow rate were shown to be the key influencing factors for the P
      recovery and energy generation. Results further show that the maximum P recovery
      corresponds to 72 mW/m2 power density. However, the energy generated at maximum P
      recovery was not the optimum; this shows that whilst P recovery and energy
      generation can be concurrently achieved in a microbial fuel cell, neither can be
      at the optimal value.

PMID- 27043585
TI  - Assessment of Exposure to VOCs among Pregnant Women in the National Children's
      Study.
AB  - Epidemiologic studies can measure exposure to volatile organic compounds (VOCs)
      using environmental samples, biomarkers, questionnaires, or observations. These
      different exposure assessment approaches each have advantages and disadvantages;
      thus, evaluating relationships is an important consideration. In the National
      Children's Vanguard Study from 2009 to 2010, participants completed
      questionnaires and data collectors observed VOC exposure sources and collected
      urine samples from 488 third trimester pregnant women at in-person study visits.
      From urine, we simultaneously quantified 28 VOC metabolites of exposure to
      acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene,
      carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene,
      ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene,
      trichloroethylene, vinyl chloride, and xylene exposures using ultra high
      performance liquid chromatography coupled with an electrospray ionization tandem
      mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using
      an ion chromatography coupled with an electrospray ionization tandem mass
      spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary
      VOC metabolite concentrations and sources of VOC exposure. Sources of exposure
      were assessed by participant report via questionnaire (use of air fresheners,
      aerosols, paint or varnish, organic solvents, and passive/active smoking) and by
      observations by a trained data collector (presence of scented products in homes).
      We found several significant (p < 0.01) relationships between the urinary
      metabolites of VOCs and sources of VOC exposure. Smoking was positively
      associated with metabolites of the tobacco constituents acrolein, acrylamide,
      acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N
      dimethylformamide, propylene oxide, styrene, and xylene. Study location was
      negatively associated with the toluene metabolite N-acetyl-S-(benzyl)-L-cysteine
      (BMA), and paint use was positively associated with the xylene metabolites 2
      methylhippuric acid (2MHA) and 3-Methylhippuric acid & 4-methylhippuric acid
      (3MHA + 4MHA). A near-significant (p = 0.06) relationship was observed between
      acrylamide metabolites and observation of incense.

PMID- 27043586
TI  - Association between Aflatoxin M1 and Liver Disease in HBV/HCV Infected Persons in
      Ghana.
AB  - Aflatoxins are produced by the fungi Aspergillus flavus and Aspergillus
      parasiticus and are common food contaminants in tropical developing countries.
      Extensive aflatoxin consumption has been shown to be highly associated with liver
      disease. A case-control study was conducted to determine the association between
      aflatoxin and liver disease in Kumasi, Ghana. A questionnaire was administered to
      examine socio-demographic characteristics and food storage and consumption
      practices, and urine samples were collected to measure levels of the aflatoxin
      metabolite (AFM1). Two hundred and seventy-six people participated in the study;
      38 had liver disease (cases), 136 had neither hepatitis B/C nor liver disease
      (negative controls), and 102 were hepatitis B/C positive without liver cancer
      (positive controls). A much higher percent of participants in each group was male
      (76% of cases, 88% of negative controls and 65% of positive controls).
      Multivariate analysis showed that age was a significant predictor for being a
      case when cases were compared to negative controls. The odds of being a case was
      70% less for participants aged 25-34 years (odds ratios (OR) 0.30; 95% confidence
      interval (CI) 0.10-0.88) compared to those >=45 years. For cases; Akans were
      seven times more likely to have AFM1 levels below the median when compared to
      other ethnic groups (OR 7; CI 1.41-34.68). When cases were compared to positive
      controls, they were 2.29 times more likely to report awareness of aflatoxin
      contamination of groundnuts (95% CI 1.06-4.91). Cases were also two times more
      likely to report awareness of aflatoxin contamination of maize than all controls
      combined (95% CI 1.02-4.11). However, most cases reported that aflatoxin
      contamination does not cause sickness in humans. This shows that there is
      awareness of aflatoxin contamination without proper understanding of the serious
      potential adverse health impacts among these study participants. These findings
      indicate that educational interventions that stress the harmful health effects of
      aflatoxin in food, with an emphasis on the higher risk for males, are urgently
      needed. The reasons for lower aflatoxin levels among Akans need to be determined,
      and the findings used to design interventions that benefit other ethnic groups in
      the society. 

PMID- 27043587
TI  - Association between Ambient Air Pollution and Asthma Prevalence in Different
      Population Groups Residing in Eastern Texas, USA.
AB  - Air pollution has been an on-going research focus due to its detrimental impact
      on human health. However, its specific effects on asthma prevalence in different
      age groups, genders and races are not well understood. Thus, the present study
      was designed to examine the association between selected air pollutants and
      asthma prevalence in different population groups during 2010 in the eastern part
      of Texas, USA.The pollutants considered were particulate matter (PM2.5 with an
      aerodynamic diameter less than 2.5 micrometers) and surface ozone. The population
      groups were categorized based on age, gender, and race. County-wise asthma
      hospital discharge data for different age, gender, and racial groups were
      obtained from Texas Asthma Control Program, Office of Surveillance, Evaluation
      and Research, Texas Department of State Health Services. The annual means of the
      air pollutants were obtained from the United States Environmental Protection
      Agency (U.S. EPA)'s air quality system data mart program. Pearson correlation
      analyzes were conducted to examine the relationship between the annual mean
      concentrations of pollutants and asthma discharge rates (ADR) for different age
      groups, genders, and races. The results reveal that there is no significant
      association or relationship between ADR and exposure of air pollutants (PM2.5,
      and O3). The study results showed a positive correlation between PM2.5 and ADR
      and a negative correlation between ADR and ozone in most of the cases. These
      correlations were not statistically significant, and can be better explained by
      considering the local weather conditions. The research findings facilitate
      identification of hotspots for controlling the most affected populations from
      further environmental exposure to air pollution, and for preventing or reducing
      the health impacts. 

PMID- 27043588
TI  - Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats.
AB  - Recently, graphene and graphene-related materials have attracted a great deal of
      attention due their unique physical, chemical, and biocompatibility properties
      and to their applications in biotechnology and medicine. However, the reports on
      the potential toxicity of graphene oxide (GO) in biological systems are very few.
      The present study investigated the response of kidneys in male Sprague-Dawley
      rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results
      showed that administration of GOs significantly increased the activities of
      superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent
      manner in the kidneys compared with control group. Serum creatinine and blood
      urea nitrogen levels were also significantly increased in rats intoxicated with
      GO compared with the control group. There was a significant elevation in the
      levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared
      to control animals. Histopathological evaluation showed significant morphological
      alterations of kidneys in GO-treated rats compared to controls. Taken together,
      the results of this study demonstrate that GO is nephrotoxic and its toxicity may
      be mediated through oxidative stress. In the present work, however, we only
      provided preliminary information on toxicity of GO in rats; further experimental
      verification and mechanistic elucidation are required before GO widely used for
      biomedical applications.

PMID- 27043589
TI  - The Association between Gene-Environment Interactions and Diseases Involving the
      Human GST Superfamily with SNP Variants.
AB  - Exposure to environmental hazards has been associated with diseases in humans.
      The identification of single nucleotide polymorphisms (SNPs) in human populations
      exposed to different environmental hazards, is vital for detecting the genetic
      risks of some important human diseases. Several studies in this field have been
      conducted on glutathione S-transferases (GSTs), a phase II detoxification
      superfamily, to investigate its role in the occurrence of diseases. Human GSTs
      consist of cytosolic and microsomal superfamilies that are further divided into
      subfamilies. Based on scientific search engines and a review of the literature,
      we have found a large amount of published articles on human GST super- and
      subfamilies that have greatly assisted in our efforts to examine their role in
      health and disease. Because of its polymorphic variations in relation to
      environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy
      metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as
      a significant biomarker. This review examines the studies on gene-environment
      interactions related to various diseases with respect to single nucleotide
      polymorphisms (SNPs) found in the GST superfamily. Overall, it can be concluded
      that interactions between GST genes and environmental factors play an important
      role in human diseases. 

PMID- 27043590
TI  - Assessment and Molecular Characterization of Human Intestinal Parasites in
      Bivalves from Orchard Beach, NY, USA.
AB  - Bivalves have been shown to be carriers of the human intestinal parasites
      Cryptosporidium parvum and Toxoplasma gondii. The goal of this study is to
      determine the prevalence of protozoan parasites in mollusks of New York City
      using a polymerase chain reaction (PCR)-based assay. Four species of mollusks,
      Mya arenaria, Geukensia demissa, Crassostrea virginica, and Mytilis edulis, were
      collected from Orchard Beach, NY in the fall of 2014, totaling 159 specimens.
      Each individual mollusk was dissected to harvest the digestive gland, the mantle,
      the gills, the foot and the siphon. The tissues were assayed for the presence of
      Cryptosporidium parvum, Giardia lamblia, and Toxoplasma gondii DNA by using
      primers that target parasite-specific genes. C. parvum was found at a prevalence
      of 50%, 11.3%, and 1%, respectively, in Mya arenaria, G. demissa, and Mytilis
      edulis. C. parvum DNA was detected in all the tissues of these bivalve species,
      except the gills. Furthermore, G. lamblia was detected in Mya arenaria, G.
      demissa, Crassostrea virginica and Mytilis edulis at a prevalence of 37.5%, 4.5%,
      60%, and 20.6%, respectively, while T. gondii DNA was not detected. 

PMID- 27043591
TI  - Erratum: Dinwiddie, G.; et al. The Impact of Educational Attainment on Observed
      Race/Ethnic Disparities in Inflammatory Risk in the 2001-2008 National Health and
      Nutrition Examination Survey. Int. J. Environ. Res. Public Health 2016, 13, 42.

PMID- 27043592
TI  - Enhanced Co-Worker Social Support in Isolated Work Groups and Its Mitigating Role
      on the Work-Family Conflict-Depression Loss Spiral.
AB  - This paper examines a loss spiral model (i.e., reciprocal relationships) between
      work-family conflict and depression, moderated by co-worker support. We expected
      that the moderation effect due to co-worker support would be evident among those
      working in isolation (i.e., mining workers) due to a greater level of intragroup
      attraction and saliency attributable to the proximity effects. We used a two wave
      panel study and data from a random population sample of Australian employees (n =
      2793, [n = 112 mining, n = 2681 non-mining]). Using structural equation modelling
      we tested the reciprocal three way interaction effects. In line with our theory,
      co-worker support buffered the reciprocal relationship between WFC and
      depression, showing a protective effect in both pathways. These moderation
      effects were found in the mining industry only suggesting a proximity component
      moderates the social support buffer hypothesis (i.e., a three way interaction
      effect). The present paper integrates previous theoretical perspectives of stress
      and support, and provides insight into the changing dynamics of workplace
      relationships. 

PMID- 27043594
TI  - Mapping Copper and Lead Concentrations at Abandoned Mine Areas Using Element
      Analysis Data from ICP-AES and Portable XRF Instruments: A Comparative Study.
AB  - Understanding spatial variation of potentially toxic trace elements (PTEs) in
      soil is necessary to identify the proper measures for preventing soil
      contamination at both operating and abandoned mining areas. Many studies have
      been conducted worldwide to explore the spatial variation of PTEs and to create
      soil contamination maps using geostatistical methods. However, they generally
      depend only on inductively coupled plasma atomic emission spectrometry (ICP-AES)
      analysis data, therefore such studies are limited by insufficient input data
      owing to the disadvantages of ICP-AES analysis such as its costly operation and
      lengthy period required for analysis. To overcome this limitation, this study
      used both ICP-AES and portable X-ray fluorescence (PXRF) analysis data, with
      relatively low accuracy, for mapping copper and lead concentrations at a section
      of the Busan abandoned mine in Korea and compared the prediction performances of
      four different approaches: the application of ordinary kriging to ICP-AES
      analysis data, PXRF analysis data, both ICP-AES and transformed PXRF analysis
      data by considering the correlation between the ICP-AES and PXRF analysis data,
      and co-kriging to both the ICP-AES (primary variable) and PXRF analysis data
      (secondary variable). Their results were compared using an independent validation
      data set. The results obtained in this case study showed that the application of
      ordinary kriging to both ICP-AES and transformed PXRF analysis data is the most
      accurate approach when considers the spatial distribution of copper and lead
      contaminants in the soil and the estimation errors at 11 sampling points for
      validation. Therefore, when generating soil contamination maps for an abandoned
      mine, it is beneficial to use the proposed approach that incorporates the
      advantageous aspects of both ICP-AES and PXRF analysis data. 

PMID- 27043593
TI  - Changes in Cosmetics Use during Pregnancy and Risk Perception by Women.
AB  - Cosmetic products contain various chemical substances that may be potential
      carcinogen and endocrine disruptors. Women's changes in cosmetics use during
      pregnancy and their risk perception of these products have not been extensively
      investigated. The main objective of this study was to describe the proportion of
      pregnant women changing cosmetics use and the proportion of non-pregnant women
      intending to do so if they became pregnant. The secondary objectives were to
      compare, among the pregnant women, the proportions of those using cosmetics
      before and during pregnancy, and to describe among pregnant and non-pregnant
      women, the risk perception of these products. A cross-sectional study was carried
      out in a gynaecology clinic and four community pharmacies. One hundred and twenty
      eight women (60 non-pregnant and 68 pregnant women) replied to a self
      administered questionnaire. Cosmetics use was identified for 28 products. The
      results showed that few women intended to change or had changed cosmetics use
      during pregnancy. Nail polish was used by fewer pregnant women compared to the
      period before pregnancy (p < 0.05). Fifty-five percent of the women considered
      cosmetics use as a risk during pregnancy and 65% would have appreciated advice
      about these products. Our findings indicate that all perinatal health
      professionals should be ready to advise women about the benefits and risks of
      using cosmetics during pregnancy. 

PMID- 27043595
TI  - Modeling Associations between Principals' Reported Indoor Environmental Quality
      and Students' Self-Reported Respiratory Health Outcomes Using GLMM and ZIP
      Models.
AB  - BACKGROUND: The aim of this paper was to examine associations between school
      building characteristics, indoor environmental quality (IEQ), and health
      responses using questionnaire data from both school principals and students.
      METHODS: From 334 randomly sampled schools, 4248 sixth grade students from 297
      schools participated in a questionnaire. From these schools, 134 principals
      returned questionnaires concerning 51 IEQ related questions of their school.
      Generalized linear mixed models (GLMM) were used to study the associations
      between IEQ indicators and existence of self-reported upper respiratory symptoms,
      while hierarchical Zero Inflated Poisson (ZIP)-models were used to model the
      number of symptoms. RESULTS: Significant associations were established between
      existence of upper respiratory symptoms and unsatisfactory classroom temperature
      during the heating season (ORs 1.45 for too hot and cold, and 1.27 for too cold
      as compared to satisfactory temperature) and dampness or moisture damage during
      the year 2006-2007 (OR: 1.80 as compared to no moisture damage), respectively.
      The number of upper respiratory symptoms was significantly associated with
      inadequate ventilation and dampness or moisture damage. A higher number of missed
      school days due to respiratory infections were reported in schools with
      inadequate ventilation (RR: 1.16). CONCLUSIONS: The school level IEQ indicator
      variables described in this paper could explain a relatively large part of the
      school level variation observed in the self-reported upper respiratory symptoms
      and missed school days due to respiratory infections among students.

PMID- 27043596
TI  - Children's Exposure to Radon in Nursery and Primary Schools.
AB  - The literature proves an evident association between indoor radon exposure and
      lung cancer, even at low doses. This study brings a new approach to the study of
      children's exposure to radon by aiming to evaluate exposure to indoor radon
      concentrations in nursery and primary schools from two districts in Portugal
      (Porto and Braganca), considering different influencing factors (occupation
      patterns, classroom floor level, year of the buildings' construction and soil
      composition of the building site), as well as the comparison with IAQ standard
      values for health protection. Fifteen nursery and primary schools in the Porto
      and Braganca districts were considered: five nursery schools for infants and
      twelve for pre-schoolers (seven different buildings), as well as eight primary
      schools. Radon measurements were performed continuously. The measured
      concentrations depended on the building occupation, classroom floor level and
      year of the buildings' construction. Although they were in general within the
      Portuguese legislation for IAQ, exceedances to international standards were
      found. These results point out the need of assessing indoor radon concentrations
      not only in primary schools, but also in nursery schools, never performed in
      Portugal before this study. It is important to extend the study to other
      microenvironments like homes, and in time to estimate the annual effective dose
      and to assess lifetime health risks. 

PMID- 27043597
TI  - Determination and Distribution of Polycyclic Aromatic Hydrocarbons in Rivers,
      Sediments and Wastewater Effluents in Vhembe District, South Africa.
AB  - Polycyclic aromatic hydrocarbons are very toxic and persistent environmental
      contaminants. This study was undertaken to assess the concentrations and possible
      sources of 16 PAHs (Polycyclic aromatic hydrocarbons) classified by the United
      State Environmental Protection Agency as priority pollutants in water and
      sediments of the Mvudi and Nzhelele Rivers. Effluents from Thohoyandou wastewater
      treatment plant and Siloam waste stabilization ponds were also investigated.
      Diagnostic ratios were used to evaluate the possible sources of PAHs. PAHs in the
      water samples were extracted using 1:1 dichloromethane and n-hexane mixtures,
      while those in the sediment samples were extracted with 1:1 acetone and
      dichloromethane using an ultrasonication method. The extracts were purified using
      an SPE technique and reconstituted in n-hexane before analyses with a gas
      chromatograph time of flight-mass spectrometer. The results obtained indicate the
      prevalence of high molecular weight PAHs in all the samples. PAHs concentrations
      in water and sediment samples from all the sampling sites were in the range of
      13.174-26.382 mg/L and 27.10-55.93 mg/kg, respectively. Combustion of biomass was
      identified as the major possible source of PAHs. Effluents from wastewater
      treatment facilities were also considered as major anthropogenic contributions to
      the levels of PAHs found in both river water and sediments. Mvudi and Nzhelele
      Rivers show moderate to high contamination level of PAHs. 

PMID- 27043598
TI  - Childhood Reports of Food Neglect and Impulse Control Problems and Violence in
      Adulthood.
AB  - Food insecurity and hunger during childhood are associated with an array of
      developmental problems in multiple domains, including impulse control problems
      and violence. Unfortunately, extant research is based primarily on small
      convenience samples and an epidemiological assessment of the hunger-violence link
      is lacking. The current study employed data from Wave 1 (2001-2002) and Wave 2
      (2004-2005) of the National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC). The NESARC is a nationally representative sample of non
      institutionalized U.S. residents aged 18 years and older. Participants who
      experienced frequent hunger during childhood had significantly greater
      impulsivity, worse self-control, and greater involvement in several forms of
      interpersonal violence. These effects were stronger among whites, Hispanics, and
      males. The findings support general theoretical models implicating impulse
      control problems as a key correlate of crime and violence and add another facet
      to the importance of ameliorating food neglect in the United States. 

PMID- 27043599
TI  - How Does Sex Influence Multimorbidity? Secondary Analysis of a Large Nationally
      Representative Dataset.
AB  - Multimorbidity increases with age and is generally more common in women, but
      little is known about sex effects on the "typology" of multimorbidity. We have
      characterized multimorbidity in a large nationally representative primary care
      dataset in terms of sex in ten year age groups from 25 years to 75 years and
      over, in a cross-sectional analysis of multimorbidity type (physical-only, mental
      only, mixed physical and mental; and commonest conditions) for 1,272,685 adults
      in Scotland. Our results show that women had more multimorbidity overall in every
      age group, which was most pronounced in the 45-54 years age group (women 26.5%
      vs. men 19.6%; difference 6.9 (95% CI 6.5 to 7.2). From the age of 45, physical
      only multimorbidity was consistently more common in men, and physical-mental
      multimorbidity more common in women. The biggest difference in physical-mental
      multimorbidity was found in the 75 years and over group (women 30.9% vs. men
      21.2%; difference 9.7 (95% CI 9.1 to 10.2). The commonest condition in women was
      depression until the age of 55 years, thereafter hypertension. In men, drugs
      misuse had the highest prevalence in those aged 25-34 years, depression for those
      aged 35-44 years, and hypertension for 45 years and over. Depression, pain,
      irritable bowel syndrome and thyroid disorders were more common in women than men
      across all age groups. We conclude that the higher overall prevalence of
      multimorbidity in women is mainly due to more mixed physical and mental health
      problems. The marked difference between the sexes over 75 years especially
      warrants further investigation. 

PMID- 27043600
TI  - Barriers to and Facilitators of the Evaluation of Integrated Community-Wide
      Overweight Intervention Approaches: A Qualitative Case Study in Two Dutch
      Municipalities.
AB  - To prevent overweight and obesity the implementation of an integrated community
      wide intervention approach (ICIA) is often advocated. Evaluation can enhance
      implementation of such an approach and demonstrate the extent of effectiveness.
      To be able to support professionals in the evaluation of ICIAs we studied
      barriers to and facilitators of ICIA evaluation. In this study ten professionals
      of two Dutch municipalities involved in the evaluation of an ICIA participated.
      We conducted semi-structured interviews (n = 12), observed programme meetings (n
      = 4) and carried out document analysis. Data were analyzed using a thematic
      content approach. We learned that evaluation is hampered when it is perceived as
      unfeasible due to limited time and budget, a lack of evaluation knowledge or a
      negative evaluation attitude. Other barriers are a poor understanding of the
      evaluation process and its added value to optimizing the programme. Sufficient
      communication between involved professionals on evaluation can facilitate
      evaluation, as does support for evaluation of ICIAs together with stakeholders at
      a strategic and tactical level. To stimulate the evaluation of ICIAs, we
      recommend supporting professionals in securing evaluation resources, providing
      tailored training and tools to enhance evaluation competences and stimulating
      strategic communication on evaluation. 

PMID- 27043601
TI  - Assessment of Ecological Risk of Heavy Metal Contamination in Coastal
      Municipalities of Montenegro.
AB  - Assessment of heavy metal concentrations in the soil samples of urban parks and
      playgrounds is very important for the evaluation of potential risks for
      residents, especially children. Until recently, there has been very little data
      about urban parks pollution in Montenegro. To evaluate the sources of potential
      contamination and concentration of heavy metals, soil samples from coastal urban
      parks and kindergartens of Montenegro were collected. Based on the heavy metal
      concentrations, multivariate analysis combined with geochemical approaches showed
      that soil samples in coastal areas of Montenegro had mean Pb and Cd
      concentrations that were over two times higher than the background values,
      respectively. Based on principal component analysis (PCA), soil pollution with
      Pb, Cd, Cu, and Zn is contributed by anthropogenic sources. Results for Cr in the
      surface soils were primarily derived from natural sources. Calculation of
      different ecological contamination factors showed that Cd is the primary
      contribution to ecological risk index (RI) origins from anthropogenic, industry,
      and urbanization sources. This data provides evidence about soil pollution in
      coastal municipalities of Montenegro. Special attention should be paid to this
      problem in order to continue further research and to consider possible ways of
      remediation of the sites where contamination has been observed. 

PMID- 27043602
TI  - Improvements in Empathy and Cognitive Flexibility after Court-Mandated
      Intervention Program in Intimate Partner Violence Perpetrators: The Role of
      Alcohol Abuse.
AB  - Research assessing the effectiveness of intervention programs for intimate
      partner violence (IPV) perpetrators has increased considerably in recent years.
      However, most of it has been focused on the analysis of psychological domains,
      neglecting neuropsychological variables and the effects of alcohol consumption on
      these variables. This study evaluated potential neuropsychological changes
      (emotional decoding, perspective taking, emotional empathy and cognitive
      flexibility) and their relationship with alcohol consumption in a mandatory
      intervention program for IPV perpetrators, as well as how these variables affect
      the risk of IPV recidivism. The sample was composed of 116 individuals with high
      alcohol (n = 55; HA) and low alcohol (n = 61; LA) consumption according to self
      report screening measures who received treatment in a IPV perpetrator
      intervention program developed in Valencia (Spain). IPV perpetrators with HA
      consumption were less accurate in decoding emotional facial signals and adopting
      others' perspective, and less cognitively flexible than those with LA consumption
      before the IPV intervention. Further, the effectiveness of the intervention
      program was demonstrated, with increases being observed in cognitive empathy
      (emotional decoding and perspective taking) and in cognitive flexibility.
      Nevertheless, the HA group showed a smaller improvement in these skills and
      higher risk of IPV recidivism than the LA group. Moreover, improvement in these
      skills was related to a lower risk of IPV recidivism. The study provides guidance
      on the targeting of cognitive domains, which are key factors for reducing IPV
      recidivism. 

PMID- 27043603
TI  - Analysis of Blood Glucose Distribution Characteristics and Its Risk Factors among
      a Health Examination Population in Wuhu (China).
AB  - BACKGROUND: Diabetes mellitus (DM) and Impaired Fasting Glucose (IFG) represent
      serious threats to human health, and as a result, this study was aimed at
      understanding the blood glucose distribution characteristics and the risk factors
      among a large health examination population in China. METHODS: An investigation
      with physical and biochemical examinations and questionnaires was conducted in
      the physical examination center from 2011 to 2014 and as a result 175,122
      physical examination attendees were enrolled in this study. Multivariate logistic
      regression was used to explore the factors influencing blood sugar levels.
      RESULTS: The rates of IFG and DM were 6.0% and 3.8%. Prevalence were 7.6%/5.1% in
      males and 5.1%/2.8% in females for IFG and DM, respectively. The prevalence of
      IFG and DM were thus higher in males than in females. In the normal group, except
      high density lipoprotein (HDL) that was significantly higher than in the IFG and
      DM group, the other indexes (age, body mass index (BMI), glucose (Glu), total
      cholesterol (TC) and total glycerides (TG) were lower than those in the IFG and
      DM group. The proportion of IFG and DM also increased with the increases in
      proportion of abnormal blood pressure, smoking and alcohol consumption.
      Multivariate logistic regression analysis showed that increasing age, high BMI,
      high TC, high TG and low HDL increased the risk of diabetes, while in males, in
      addition to the above factors, the smoking and drinking factors also increased
      the risk of diabetes. After the age of 65, the blood glucose level reached a peak
      in males, while in females, the increasing trends was on the rise. The inflexion
      age of the fast rise was younger in males than in females. CONCLUSION: The study
      population showed a high prevalence of DM and IFG among the adults. Regular
      physical examination for the early detection of diabetes is recommended in the
      high-risk population.

PMID- 27043604
TI  - Prevalence and Associated Factors of Secondhand Smoke Exposure among Internal
      Chinese Migrant Women of Reproductive Age: Evidence from China's Labor-Force
      Dynamic Survey.
AB  - Secondhand smoke (SHS) is a major risk factor for poor health outcomes among
      women in China, where proportionately few women smoke. This is especially the
      case as it pertains to women's reproductive health, specifically migrant women
      who are exposed to SHS more than the population at large. There are several
      factors which may increase migrant women's risk of SHS exposure. This paper aims
      to investigate the prevalence and associated factors of SHS exposure among
      internal Chinese migrant women of reproductive age. The data used were derived
      from the 2014 Chinese Labor Dynamic Survey, a national representative panel
      survey. The age-adjusted rate of SHS exposure of women of reproductive age with
      migration experience was of 43.46% (95% CI: 40.73%-46.40%), higher than those
      without migration experience (35.28% (95% CI: 33.66%-36.97%)). Multivariate
      analysis showed that participants with a marital status of "Widowed" had
      statistically lower exposure rates, while those with a status of "Cohabitation"
      had statistically higher exposure. Those with an undergraduate degree or above
      had statistically lower SHS exposure. Those with increasing levels of social
      support, and those who currently smoke or drink alcohol, had statistically higher
      SHS exposure. Participants' different work-places had an effect on their SHS
      exposure, with outdoor workers statistically more exposed. Our findings suggest
      that urgent tobacco control measures should be taken to reduce smoking prevalence
      and SHS exposure. Specific attention should be paid to protecting migrant women
      of reproductive age from SHS. 

PMID- 27043605
TI  - Optimum Installation of Sorptive Building Materials Using Contribution Ratio of
      Pollution Source for Improvement of Indoor Air Quality.
AB  - Reinforcing the insulation and airtightness of buildings and the use of building
      materials containing new chemical substances have caused indoor air quality
      problems. Use of sorptive building materials along with removal of pollutants,
      constant ventilation, bake-out, etc. are gaining attention in Korea and Japan as
      methods for improving such indoor air quality problems. On the other hand,
      sorptive building materials are considered a passive method of reducing the
      concentration of pollutants, and their application should be reviewed in the
      early stages. Thus, in this research, activated carbon was prepared as a sorptive
      building material. Then, computational fluid dynamics (CFD) was conducted, and a
      method for optimal installation of sorptive building materials was derived
      according to the indoor environment using the contribution ratio of pollution
      source (CRP) index. The results show that a method for optimal installation of
      sorptive building materials can be derived by predicting the contribution ratio
      of pollutant sources according to the CRP index. 

PMID- 27043606
TI  - Structural Factors Affecting Health Examination Behavioral Intention.
AB  - Disease screening instruments used for secondary prevention can facilitate early
      determination and treatment of pathogenic factors, effectively reducing disease
      incidence, mortality rates, and health complications. Therefore, people should be
      encouraged to receive health examinations for discovering potential pathogenic
      factors before symptoms occur. Here, we used the health belief model as a
      foundation and integrated social psychological factors and investigated the
      factors influencing health examination behavioral intention among the public in
      Taiwan. In total, 388 effective questionnaires were analyzed through structural
      model analysis. Consequently, this study yielded four crucial findings: (1) The
      established extended health belief model could effectively predict health
      examination behavioral intention; (2) Self-efficacy was the factor that most
      strongly influenced health examination behavioral intention, followed by health
      knowledge; (3) Self-efficacy substantially influenced perceived benefits and
      perceived barriers; (4) Health knowledge and social support indirectly influenced
      health examination behavioral intention. The preceding results can effectively
      increase the acceptance and use of health examination services among the public,
      thereby facilitating early diagnosis and treatment and ultimately reducing
      disease and mortality rates. 

PMID- 27043607
TI  - Correlates of Insufficient Physical Activity among Junior High School Students: A
      Cross-Sectional Study in Xi'an, China.
AB  - BACKGROUND: Physical activity plays an important role in individual health at all
      stages of life. However, evidence is lacking regarding the level of moderate to
      vigorous physical activity (MVPA) and the related factors to insufficient
      physical activity (IPA). METHODS: A sample of 1060 students aged 12-15 years from
      nine public junior high schools in China were invited to participate in this
      study. Physical activity was assessed by a modified version of the International
      Physical Activity Questionnaire. Logistic regression was used to assess the
      factors associated with IPA. RESULTS: 30.1% boys and 43.0% girls in our sample
      did not engage in sufficient physical activity. Obesity (OR = 2.2, 95% CI: 1.5
      2.9) and high socioeconomic status (SES) (OR = 2.4, 95% CI: 1.3-4.8) were
      positively associated with IPA, whereas male sex (OR = 0.7, 95% CI: 0.5-0.9),
      underweight status (OR = 0.5, 95% CI: 0.3-0.7), and high family support level for
      physical activity (OR = 0.7, 95% CI: 0.6-0.9) showed inverse associations. Age
      was not associated with IPA. CONCLUSIONS: IPA appears to be a considerable
      problem in this sample of Chinese youth. Effective interventions to increase
      physical activity are needed and may include improving family support level for
      physical activity, especially for girls, the obese and those with high SES.

PMID- 27043609
TI  - Introduction to the Special Issue on Gender and Geoethics in the Geosciences.
AB  - In this introduction to the Special Issue on Gender and Geoethics in the
      Geosciences is a focus on the participation of women in traditionally male
      dominated professions, with geography as an exemplary academic subject. The
      Special Issue stems from the Commission of Gender and Geoethics as part of the
      International Association of Geoethics, and endeavors to bring together efforts
      at various spatial scales that examine the position of women in science and
      engineering in particular, as conveyed in engineering geology, disaster
      management sciences, and climate change adaptation studies. It has been
      discovered, for instance, that men are more active and personally prepared at the
      community level (in Atlantic Canada coastal communities), and more action is
      still required in developing countries especially to promote gender equality and
      empower women. Studies contained in this Special Issue also reveal that tutoring
      and mentoring by other women can promote further involvement in non-traditional
      professions, such as professional engineering geology, where women are preferring
      more traditional (less applied) approaches that may circumscribe their ability to
      find suitable employment after graduation. Moreover, the hiring policy needs to
      change in many countries, such as Canada, where there are fewer women at entry
      level and senior ranks within geography, especially in physical geography as the
      scientific part of the discipline. The exclusion of women in traditionally male
      dominated spheres needs to be addressed and rectified for the ascent of women to
      occur in scientific geography and in other geosciences as well as science and
      engineering at large. 

PMID- 27043608
TI  - Effects of 20 Selected Fruits on Ethanol Metabolism: Potential Health Benefits
      and Harmful Impacts.
AB  - The consumption of alcohol is often accompanied by other foods, such as fruits
      and vegetables. This study is aimed to investigate the effects of 20 selected
      fruits on ethanol metabolism to find out their potential health benefits and
      harmful impacts. The effects of the fruits on ethanol metabolism were
      characterized by the concentrations of ethanol and acetaldehyde in blood, as well
      as activities of alcohol dehydrogenase and acetaldehyde dehydrogenase in liver of
      mice. Furthermore, potential health benefits and harmful impacts of the fruits
      were evaluated by biochemical parameters including aspartate transaminase (AST),
      alanine transferase (ALT), malondialdehyde, and superoxide dismutase. Generally,
      effects of these fruits on ethanol metabolism were very different. Some fruits
      (such as Citrus limon (yellow), Averrhoa carambola, Pyrus spp., and Syzygium
      samarangense) could decrease the concentration of ethanol in blood. In addition,
      several fruits (such as Cucumis melo) showed hepatoprotective effects by
      significantly decreasing AST or ALT level in blood, while some fruits (such as
      Averrhoa carambola) showed adverse effects. The results suggested that the
      consumption of alcohol should not be accompanied by some fruits, and several
      fruits could be developed as functional foods for the prevention and treatment of
      hangover and alcohol use disorder. 

PMID- 27043610
TI  - Recombinant Pseudorabies Virus (PRV) Expressing Firefly Luciferase Effectively
      Screened for CRISPR/Cas9 Single Guide RNAs and Antiviral Compounds.
AB  - A Pseudorabies virus (PRV) variant has emerged in China since 2011 that is not
      protected by commercial vaccines, and has not been well studied. The PRV genome
      is large and difficult to manipulate, but it is feasible to use clustered,
      regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology.
      However, identification of single guide RNA (sgRNA) through screening is critical
      to the CRISPR/Cas9 system, and is traditionally time and labor intensive, and not
      suitable for rapid and high throughput screening of effective PRV sgRNAs. In this
      study, we developed a recombinant PRV strain expressing firefly luciferase and
      enhanced green fluorescent protein (EGFP) as a reporter virus for PRV-specific
      sgRNA screens and rapid evaluation of antiviral compounds. Luciferase activity
      was apparent as soon as 4 h after infection and was stably expressed through 10
      passages. In a proof of the principle screen, we were able to identify several
      PRV specific sgRNAs and confirmed that they inhibited PRV replication using
      traditional methods. Using the reporter virus, we also identified PRV variants
      lacking US3, US2, and US9 gene function, and showed anti-PRV activity for
      chloroquine. Our results suggest that the reporter PRV strain will be a useful
      tool for basic virology studies, and for developing PRV control and prevention
      measures. 

PMID- 27043611
TI  - Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.
AB  - Marburg virus causes severe and often lethal viral disease in humans, and there
      are currently no Food and Drug Administration (FDA) approved medical
      countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for
      evaluation of countermeasures in humans, so therapeutic and vaccine candidates
      can only be approved through the FDA animal rule-a mechanism requiring well
      characterized animal models in which efficacy would be evaluated. Here, we
      describe a natural history study where rhesus macaques were surgically implanted
      with telemetry devices and central venous catheters prior to aerosol exposure
      with Marburg-Angola virus, enabling continuous physiologic monitoring and blood
      sampling without anesthesia. After a three to four day incubation period, all
      animals developed fever, viremia, and lymphopenia before developing tachycardia,
      tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D
      dimer levels and elevated pro-inflammatory cytokines suggesting a systemic
      inflammatory response with organ failure. The final, terminal period began with
      the onset of sustained hypotension, dehydration progressed with signs of major
      organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and
      ended with euthanasia or death. The most significant pathologic findings were
      marked infection of the respiratory lymphoid tissue with destruction of the
      tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the
      liver, and splenitis. 

PMID- 27043612
TI  - Enterovirus Control of Translation and RNA Granule Stress Responses.
AB  - Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved
      several parallel strategies to regulate cellular gene expression and stress
      responses to ensure efficient expression of the viral genome. Enteroviruses
      utilize their encoded proteinases to take over the cellular translation apparatus
      and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to
      control and repress the two main types of cytoplasmic RNA granules, stress
      granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive
      dynamic structures involved in repression of gene expression. This review
      discusses these processes and the current understanding of the underlying
      mechanisms with respect to enterovirus infections. In addition, the review
      discusses accumulating data suggesting linkage exists between RNA granule
      formation and innate immune sensing and activation. 

PMID- 27043614
TI  - Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the
      Structure of Drug-Loaded Liposomes.
AB  - Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized
      as efficient platforms for delivering therapeutic agents, especially those with
      low solubility in water. Besides being safe and non-toxic, drug carriers with
      improved performance should meet the requirements of (i) appropriate size and
      shape and (ii) cargo upload/release with unmodified properties. Structural issues
      are of primary importance to control the mechanism of action of loaded vectors.
      Overall properties, such as mean diameter and surface charge, can be obtained
      using bench instruments (Dynamic Light Scattering and Zeta potential). However,
      techniques with higher space and time resolution are needed for in-depth
      structural characterization. Small-angle X-ray (SAXS) and neutron (SANS)
      scattering techniques provide information at the nanoscale and have therefore
      been largely used to investigate nanovectors loaded with drugs or other
      biologically relevant molecules. Here we revise recent applications of these
      complementary scattering techniques in the field of drug delivery in
      pharmaceutics and medicine with a focus to liposomal carriers. In particular, we
      highlight those aspects that can be more commonly accessed by the interested
      users. 

PMID- 27043613
TI  - Next-Generation Sequencing in the Understanding of Kaposi's Sarcoma-Associated
      Herpesvirus (KSHV) Biology.
AB  - Non-Sanger-based novel nucleic acid sequencing techniques, referred to as Next
      Generation Sequencing (NGS), provide a rapid, reliable, high-throughput, and
      massively parallel sequencing methodology that has improved our understanding of
      human cancers and cancer-related viruses. NGS has become a quintessential
      research tool for more effective characterization of complex viral and host
      genomes through its ever-expanding repertoire, which consists of whole-genome
      sequencing, whole-transcriptome sequencing, and whole-epigenome sequencing. These
      new NGS platforms provide a comprehensive and systematic genome-wide analysis of
      genomic sequences and a full transcriptional profile at a single nucleotide
      resolution. When combined, these techniques help unlock the function of novel
      genes and the related pathways that contribute to the overall viral pathogenesis.
      Ongoing research in the field of virology endeavors to identify the role of
      various underlying mechanisms that control the regulation of the herpesvirus
      biphasic lifecycle in order to discover potential therapeutic targets and
      treatment strategies. In this review, we have complied the most recent findings
      about the application of NGS in Kaposi's sarcoma-associated herpesvirus (KSHV)
      biology, including identification of novel genomic features and whole-genome KSHV
      diversities, global gene regulatory network profiling for intricate transcriptome
      analyses, and surveying of epigenetic marks (DNA methylation, modified histones,
      and chromatin remodelers) during de novo, latent, and productive KSHV infections.

PMID- 27043615
TI  - Barriers to and Facilitators of the Consumption of Animal-Based Protein-Rich
      Foods in Older Adults.
AB  - Protein intakes in the older population can be lower than recommended for good
      health, and while reasons for low protein intakes can be provided, little work
      has attempted to investigate these reasons in relation to actual intakes, and so
      identify those of likely greatest impact when designing interventions.
      Questionnaires assessing: usual consumption of meat, fish, eggs and dairy
      products; agreement/disagreement with reasons for the consumption/non-consumption
      of these foods; and several demographic and lifestyle characteristics; were sent
      to 1000 UK community-dwelling adults aged 65 years and over. In total, 351
      returned questionnaires, representative of the UK older population for gender and
      age, were suitable for analysis. Different factors were important for consumption
      of the four food groups, but similarities were also found. These similarities
      likely reflect issues of particular concern to both the consumption of animal
      based protein-rich foods and the consumption of these foods by older adults.
      Taken together, these findings suggest intakes to be explained by, and thus that
      strategies for increasing consumption should focus on: increasing
      liking/tastiness; improving convenience and the effort required for food
      preparation and consumption; minimizing spoilage and wastage; and improving
      perceptions of affordability or value for money; freshness; and the healthiness
      of protein-rich foods. 

PMID- 27043617
TI  - The Performance of Five Bioelectrical Impedance Analysis Prediction Equations
      against Dual X-ray Absorptiometry in Estimating Appendicular Skeletal Muscle Mass
      in an Adult Australian Population.
AB  - Appendicular skeletal muscle mass (ASM) is a diagnostic criterion for sarcopenia.
      Bioelectrical impedance analysis (BIA) offers a bedside approach to measure ASM
      but the performance of BIA prediction equations (PE) varies with ethnicities and
      body composition. We aim to validate the performance of five PEs in estimating
      ASM against estimation by dual-energy X-ray absorptiometry (DXA). We recruited
      195 healthy adult Australians and ASM was measured using single-frequency BIA.
      Bland-Altman analysis was used to assess the predictive accuracy of ASM as
      determined by BIA against DXA. Precision (root mean square error (RMSE)) and bias
      (mean error (ME)) were calculated according to the method of Sheiner and Beal.
      Four PEs (except that by Kim) showed ASM values that correlated strongly with
      ASMDXA (r ranging from 0.96 to 0.97, p < 0.001). The Sergi equation performed the
      best with the lowest ME of -1.09 kg (CI: -0.84--1.34, p < 0.001) and the RMSE was
      2.09 kg (CI: 1.72-2.47). In men, the Kyle equation performed better with the
      lowest ME (-0.32 kg (CI: -0.66-0.02) and RMSE (1.54 kg (CI: 1.14-1.93)). The
      Sergi equation is applicable in adult Australians (Caucasian) whereas the Kyle
      equation can be considered in males. The need remains to validate PEs in other
      ethnicities and to develop equations suitable for multi-frequency BIA. 

PMID- 27043616
TI  - Nutrition and Inflammation in Older Individuals: Focus on Vitamin D, n-3
      Polyunsaturated Fatty Acids and Whey Proteins.
AB  - Chronic activation of the inflammatory response, defined as inflammaging, is the
      key physio-pathological substrate for anabolic resistance, sarcopenia and frailty
      in older individuals. Nutrients can theoretically modulate this phenomenon. The
      underlying molecular mechanisms reducing the synthesis of pro-inflammatory
      mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated
      fatty acids (PUFA) and whey proteins. In this paper, we review the current
      evidence emerging from observational and intervention studies, performed in older
      individuals, either community-dwelling or hospitalized with acute disease, and
      evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on
      inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1),
      interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). After the
      analysis, we conclude that there is sufficient evidence for an anti-inflammatory
      effect in aging only for n-3 PUFA intake, while the few existing intervention
      studies do not support a similar activity for vitamin D and whey supplements.
      There is need in the future of large, high-quality studies testing the effects of
      combined dietary interventions including the above mentioned nutrients on
      inflammation and health-related outcomes. 

PMID- 27043618
TI  - Enzymatically-Processed Wheat Bran Enhances Macrophage Activity and Has in Vivo
      Anti-Inflammatory Effects in Mice.
AB  - Wheat bran is a rich source of dietary fiber, of which arabinoxylan is the most
      abundant non-starch polysaccharide. Arabinoxylan has been known to exert in vivo
      immunological activities. Based on prior findings, we pretreated wheat bran with
      enzymatic hydrolysis to increase the release of soluble arabinoxylan and
      investigated whether oral administration of wheat bran altered macrophage
      activity in a mouse model. After four weeks of treatment, we isolated peritoneal
      macrophages for phagocytic receptor analysis and lipopolysaccharide (LPS)-induced
      inflammatory changes. In the second experiment, mice given wheat bran were
      intraperitoneally stimulated with LPS and serum levels of pro- and anti
      inflammatory cytokines were determined. The expression of SRA and CD36, and
      phagocytic activity increased (p < 0.05, respectively). Ex vivo stimulation of
      macrophages by LPS resulted in reduced surface expression of CD40 (p < 0.05) and
      decreased production of nitric oxide (p < 0.005), tumor necrosis factor (TNF)
      alpha (p < 0.005), interleukin (IL)-6 (p < 0.01), and IL-12 (p < 0.05). Mice
      treated with wheat bran showed decreased levels of serum TNF-alpha and IL-6 (p <
      0.05, respectively) and an increased level of serum anti-inflammatory IL-10 (p <
      0.05) in response to intraperitoneal LPS. Enzymatically-processed wheat bran
      boosts macrophage phagocytic capacity possibly through up-regulation of scavenger
      receptors and confers anti-inflammatory effects, indicating its potential as an
      immuno-enhancing functional food. 

PMID- 27043619
TI  - Vitamin D Deficiency is Associated with Overweight and/or Obesity among
      Schoolchildren in Central Ethiopia: A Cross-Sectional Study.
AB  - Childhood and adolescent obesity is an international public health problem
      leading to an increased risk of adulthood obesity, mortality and morbidity. Its
      prevalence is increasing in low-income populations, and we hypothesized it may be
      associated with vitamin D deficiency. Low vitamin D status is a worldwide public
      health issue including in Ethiopia; however, no one has examined
      overweight/obesity in Ethiopian schoolchildren with regard to vitamin D status.
      The Analyses of a data set from a school-based cross-sectional study conducted in
      Adama Town (n = 89) and in rural Adama Woreda (n = 85) was carried out to
      determine vitamin D deficiency and its association with overweight and/or
      obesity. Data on a total of 174 schoolchildren aged 11-18 years was used for
      these analyses. The overall prevalence of overweight and/or obesity was 10.3%,
      with 8.5% overweight and 2.3% obese; the prevalence of underweight was 19%. In
      the multivariable logistic regression model, vitamin D deficiency, being in the
      higher age group, female sex and urban residence of students, their mothers'
      occupation of being employed and their households' high and middle socioeconomic
      status were significantly associated with overweight and/or obesity. We concluded
      that vitamin D deficiency is an independent predictor significantly associated
      with overweight and/or obesity among schoolchildren from rural and urban settings
      in Ethiopia. The results imply the need for behavior change communications on the
      importance of exposure to sunlight to produce adequate vitamin D to curb this
      emerging health problem of overweight/obesity following economic growth and
      globalization in Ethiopia. As this study only highlighted the association,
      prospective studies and randomized controlled trials are required to establish
      causality. 

PMID- 27043620
TI  - Association between Parent and Child Dietary Sodium and Potassium Intakes as
      Assessed by 24-h Urinary Excretion.
AB  - The aim of this study was to assess the association between parent and child
      sodium (Na) and potassium (K) intake as assessed by 24-h urinary excretion
      (24hUE). Primary school children and their parent(s) provided one 24-h urine
      sample and information on cooking and children's discretionary salt use. Valid
      urine samples were provided by 108 mothers (mean age 41.8 (5.1) (SD) years, Na
      120 (45) mmol/day) (7.0 g/day salt equivalent) and 40 fathers (44.4 (4.9) years,
      Na 152 (49) mmol/day (8.9 g/day salt), and 168 offspring (51.8% male, age 9.1
      (2.0) years, Na 101 (47) mmol/day (5.9 g/day salt). When adjusted for parental
      age, child age and gender a 17 mmol/day Na (1 g/day salt) increase in mother's
      24hUE was associated with a 3.4 mmol/day Na (0.2 g/day salt) increase in child's
      salt 24hUE (p = 0.04) with no association observed between father and child.
      Sixty-seven percent of parents added salt during cooking and 37% of children
      added salt at the table. Children who reported adding table salt had higher
      urinary excretion than those who did not (p = 0.01). The association between
      mother and child Na intake may relate to the consumption of similar foods and
      highlights the importance of the home environment in influencing total dietary
      sodium intake. 

PMID- 27043621
TI  - Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma
      Effect of Cyclophosphamide.
AB  - The use of a mixture of amino acids caused a selective apoptosis induction
      against a variety of tumor cell lines, reduced the adverse effects of anti-cancer
      drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We
      evaluated the effects and underlying mechanisms of soy-derived multiple amino
      acids' oral supplementation on the therapeutic efficacy of low-dose
      cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe
      combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180)
      cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect
      on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and
      oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived
      multiple amino acid supplement indicated that the soy-derived multiple amino acid
      supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl
      2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated
      autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar
      responses as CTX plus soy-derived multiple amino acid in downregulating autophagy
      and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived
      multiple amino acid supplement had a potent anti-tumor effect mediated through
      downregulation of autophagy and upregulation of apoptosis. 

PMID- 27043623
TI  - Characteristics of U.S. Adults with Usual Daily Folic Acid Intake above the
      Tolerable Upper Intake Level: National Health and Nutrition Examination Survey,
      2003-2010.
AB  - The Food and Drug Administration mandated that by 1998, all enriched cereal grain
      products (ECGP) be fortified with folic acid in order to prevent the occurrence
      of neural tube defects. The Institute of Medicine established the tolerable upper
      intake level (UL) for folic acid (1000 ug/day for adults) in 1998. We
      characterized U.S. adults with usual daily folic acid intake exceeding the UL.
      Using NHANES 2003-2010 data, we estimated the percentage of 18,321 non-pregnant
      adults with usual daily folic acid intake exceeding the UL, and among them, we
      calculated the weighted percentage by sex, age, race/ethnicity, sources of folic
      acid intake, supplement use and median usual daily folic acid intakes. Overall,
      2.7% (standard error 0.6%) of participants had usual daily intake exceeding the
      UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5%
      took supplements containing folic acid. When stratified by sex and age groups
      among those with usual daily folic acid intake exceeding the UL, 20.8% were women
      aged 19-39 years. Those with usual daily intake exceeding the folic acid UL were
      more likely to be female, non-Hispanic white, supplement users or to have at
      least one chronic medical condition compared to those not exceeding the folic
      acid UL. Among those with usual daily folic acid intake exceeding the UL who also
      took supplements, 86.6% took on average >400 ug of folic acid/day from
      supplements. Everyone with usual daily folic acid intake exceeding the UL
      consumed folic acid from multiple sources. No one in our study population had
      usual daily folic acid intake exceeding the UL through consumption of mandatorily
      fortified enriched cereal grain products alone. Voluntary consumption of
      supplements containing folic acid is the main factor associated with usual daily
      intake exceeding the folic acid UL. 

PMID- 27043622
TI  - Protective Activity of Total Polyphenols from Genista quadriflora Munby and
      Teucrium polium geyrii Maire in Acetaminophen-Induced Hepatotoxicity in Rats.
AB  - Oxidative stress is a major cause of drug-induced hepatic diseases and several
      studies have demonstrated that diet supplementation with plants rich in
      antioxidant compounds provides a variety of health benefits in these
      circumstances. Genista quadriflora Munby (Gq) and Teucrium polium geyrii Maire
      (Tp) are known to possess antioxidant and numerous biological properties and
      these endemic plants are often used for dietary or medicinal applications.
      Herein, we evaluated the beneficial effect of rich-polyphenol fractions of Gq and
      Tp to prevent Acetaminophen-induced liver injury and investigated the mechanisms
      involved in this protective action. Rats were orally administered polyphenolic
      extracts from Gq or Tp (300 mg/kg) or N-acetylcysteine (NAC: 200 mg/kg) once
      daily for ten days prior to the single oral administration of Acetaminophen
      (APAP: 1 g/kg). The results show that preventive administration of polyphenolic
      extracts from Gq or Tp exerts a hepatoprotective influence during APAP treatment
      by improving transaminases leakage and liver histology and stimulating
      antioxidant defenses. Besides, suppression of liver CYP2E1, GSTpi and TNF-alpha
      mRNA levels, with enhancement of mitochondrial bioenergetics may contribute to
      the observed hepatoprotection induced by Gq and Tp extracts. The effect of Tp
      extract is significantly higher (1.5-2 fold) than that of Gq extract and NAC
      regarding the enhancement of mitochondrial functionality. Overall, this study
      brings the first evidence that pretreatment with these natural extracts display
      in vivo protective activity against APAP hepatotoxicity through improving
      mitochondrial bioenergetics, oxidant status, phase I and II enzymes expression
      and inflammatory processes probably by virtue of their high total polyphenols
      content. 

PMID- 27043624
TI  - Low Prevalence of Iron and Vitamin A Deficiency among Cambodian Women of
      Reproductive Age.
AB  - Nearly half of women of reproductive age (WRA) in Cambodia are anemic. To guide
      interventions, national data on nutritional causes of anemia, including iron
      deficiency and vitamin A deficiency, are needed. In 2012, a national household
      survey in WRA on antibodies to routine vaccine-preventable disease immunity was
      performed. We used serum samples from this survey to estimate the prevalence of
      iron and vitamin A deficiency in 2112 Cambodian WRA, aged 15 to 39 years. Iron
      deficiency was classified as low or marginal iron stores (ferritin concentrations
      corrected for inflammation <15 MUg/L and <50 MUg/L respectively; Fer), iron
      deficient erythropoiesis (soluble transferrin receptor concentrations >8.3 mg/L;
      sTfR), or low total body iron (TBI) derived from Fer and sTfR concentrations (<0
      mg/kg). Vitamin A status was classified using retinol binding protein (RBP)
      concentrations corrected for inflammation as deficient (<0.70 MUmol/L) or
      marginal (<1.05 MUmol/L. Overall, the prevalence of low iron stores, low TBI and
      iron deficient erythropoiesis was 8.1%, 5.0% and 9.3% respectively. Almost 40% of
      the women had marginal iron stores. Iron status was better in women living in
      urban areas compared to rural areas (p < 0.05 for TBI and sTfR). The prevalence
      of vitamin A deficiency was <1%. These findings suggest that the contribution of
      iron and vitamin A deficiency to the high prevalence of anemia in Cambodian WRA
      may be limited. The etiology of anemia in Cambodia needs to be elucidated further
      to guide current policies on anemia. 

PMID- 27043625
TI  - ADAM10 Cell Surface Expression but Not Activity Is Critical for Staphylococcus
      aureus alpha-Hemolysin-Mediated Activation of the NLRP3 Inflammasome in Human
      Monocytes.
AB  - The Staphylococcus aureus toxin, alpha-hemolysin, is an important and well
      studied virulence factor in staphylococcal infection. It is a soluble monomeric
      protein that, once secreted by the bacterium, forms a heptameric pore in the
      membrane of a broad range of host cell types. Hemolysin was recently discovered
      to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial
      and endothelial cells, ADAM10 activation is required for the toxin's activity
      against these cells. In host monocytic cells, alpha-hemolysin activates the
      nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin
      domain containing 3 (NLRP3) inflammasome leading to production of pro
      inflammatory cytokines and cell death. We now show that ADAM10 is critical for
      alpha-hemolysin-mediated activation of the NLRP3 inflammasome in human monocytes
      as siRNA knockdown or chemical blockade of ADAM10-alpha-hemolysin interaction
      leads to diminished inflammasome activation and cell death by reducing the
      available ADAM10 on the cell surface. Unlike epithelial cell and endothelial cell
      damage, which requires alpha-hemolysin induced ADAM10 activation, ADAM10 protease
      activity was not required for NLRP3 inflammasome activation. This work confirms
      the importance of ADAM10 in immune activation by alpha-hemolysin, but indicates
      that host cell signal induction by the toxin is different between host cell
      types. 

PMID- 27043626
TI  - Mechanisms that Determine the Differential Stability of Stx+ and Stx(-) Lysogens.
AB  - Phages 933W, BAA2326, 434, and lambda are evolutionarily-related temperate
      lambdoid phages that infect Escherichia coli. Although these are highly-similar
      phages, BAA2326 and 933W naturally encode Shiga toxin 2 (Stx+), but phage 434 and
      lambda do not (Stx(-)). Previous reports suggest that the 933W Stx+ prophage
      forms less stable lysogens in E. coli than does the Stx(-) prophages lambda, P22,
      and 434. The higher spontaneous induction frequency of the Stx+ prophage may be
      correlated with both virulence and dispersion of the Stx2-encoding phage. Here,
      we examined the hypothesis that lysogen instability is a common feature of Stx+
      prophages. We found in both the absence and presence of prophage inducers (DNA
      damaging agents, salts), the Stx+ prophages induce at higher frequencies than do
      Stx(-) prophages. The observed instability of Stx+ prophages does not appear to
      be the result of any differences in phage development properties between Stx+ and
      Stx(-) phages. Our results indicate that differential stability of Stx+ and Stx(
      ) prophages results from both RecA-dependent and RecA-independent effects on the
      intracellular concentration of the respective cI repressors. 

PMID- 27043627
TI  - Structural Characterization of Humanized Nanobodies with Neutralizing Activity
      against the Bordetella pertussis CyaA-Hemolysin: Implications for a Potential
      Epitope of Toxin-Protective Antigen.
AB  - Previously, the 126-kDa CyaA-hemolysin (CyaA-Hly) fragment cloned from Bordetella
      pertussis--the causative agent of whooping cough--and functionally expressed in
      Escherichia coli was revealed as a key determinant for CyaA-mediated hemolysis
      against target erythrocytes. Here, phagemid-transfected E. coli clones producing
      nanobodies capable of binding to CyaA-Hly were selected from a humanized-camel
      VH/VHH phage-display library. Subsequently verified for binding activities by
      indirect ELISA and Western blotting, four CyaA-Hly-specific nanobodies were
      obtained and designated according to the presence/absence of VHH-hallmark amino
      acids as VHH2, VH5, VH18 and VHH37. In vitro neutralization assay revealed that
      all four ~17-kDa His-tagged VH/VHH nanobodies, in particular VHH37, which were
      over-expressed as inclusions and successfully unfolded-refolded, were able to
      effectively inhibit CyaA-Hly-mediated hemolysis. Phage-mimotope searching
      revealed that only peptides with sequence homologous to Linker 1 connecting
      Blocks I and II within the CyaA-RTX subdomain were able to bind to these four
      CyaA-Hly-specific nanobodies. Structural analysis of VHH37 via homology modeling
      and intermolecular docking confirmed that this humanized nanobody directly
      interacts with CyaA-RTX/Linker 1 through multiple hydrogen and ionic bonds.
      Altogether, our present data demonstrate that CyaA-RTX/Linker 1 could serve as a
      potential epitope of CyaA-protective antigen that may be useful for development
      of peptide-based pertussis vaccines. Additionally, such toxin-specific nanobodies
      have a potential for test-driven development of a ready-to-use therapeutic in
      passive immunization for mitigation of disease severity.

PMID- 27043628
TI  - Heated Debates: Hot-Water Immersion or Ice Packs as First Aid for Cnidarian
      Envenomations?
AB  - Cnidarian envenomations are an important public health problem, responsible for
      more deaths than shark attacks annually. For this reason, optimization of first
      aid care is essential. According to the published literature, cnidarian venoms
      and toxins are heat labile at temperatures safe for human application, which
      supports the use of hot-water immersion of the sting area(s). However, ice packs
      are often recommended and used by emergency personnel. After conducting a
      systematic review of the evidence for the use of heat or ice in the treatment of
      cnidarian envenomations, we conclude that the majority of studies to date support
      the use of hot-water immersion for pain relief and improved health outcomes. 

PMID- 27043629
TI  - EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium
      perfringens Iota Toxin and Clostridium botulinum C2 Toxin.
AB  - The pathogenic bacteria Clostridium difficile, Clostridium perfringens and
      Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota
      and C2, respectively. These toxins are composed of a transport component (B) and
      a separate enzyme component (A). When both components assemble on the surface of
      mammalian target cells, the B components mediate the entry of the A components
      via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin,
      resulting in depolymerization of F-actin, cell-rounding and eventually death. In
      the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6
      dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple
      toxins and viruses, also protects different mammalian epithelial cells from all
      three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the
      intoxication of cells with Clostridium difficile toxins A and B, indicating a
      possible different entry route for this toxin. EGA does not affect either the
      binding of the C2 toxin to the cells surface or the enzyme activity of the A
      components of CDT, iota and C2, suggesting that this compound interferes with
      cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA
      inhibits the pH-dependent transport of the A component across cell membranes. EGA
      is not cytotoxic, and therefore, we propose it as a lead compound for the
      development of novel pharmacological inhibitors against clostridial binary actin
      ADP-ribosylating toxins.

PMID- 27043630
TI  - Detection and Quantification of ADP-Ribosylated RhoA/B by Monoclonal Antibody.
AB  - Clostridium botulinum exoenzyme C3 is the prototype of C3-like ADP
      ribosyltransferases that modify the GTPases RhoA, B, and C. C3 catalyzes the
      transfer of an ADP-ribose moiety from the co-substrate nicotinamide adenine
      dinucleotide (NAD) to asparagine-41 of Rho-GTPases. Although C3 does not possess
      cell-binding/-translocation domains, C3 is able to efficiently enter intact
      cells, including neuronal and macrophage-like cells. Conventionally, the
      detection of C3 uptake into cells is carried out via the gel-shift assay of
      modified RhoA. Since this gel-shift assay does not always provide clear,
      evaluable results an additional method to confirm the ADP-ribosylation of RhoA is
      necessary. Therefore, a new monoclonal antibody has been generated that
      specifically detects ADP-ribosylated RhoA/B, but not RhoC, in Western blot and
      immunohistochemical assay. The scFv antibody fragment was selected by phage
      display using the human naive antibody gene libraries HAL9/10. Subsequently, the
      antibody was produced as scFv-Fc and was found to be as sensitive as a
      commercially available RhoA antibody providing reproducible and specific results.
      We demonstrate that this specific antibody can be successfully applied for the
      analysis of ADP-ribosylated RhoA/B in C3-treated Chinese hamster ovary (CHO) and
      HT22 cells. Moreover, ADP-ribosylation of RhoA was detected within 10 min in C3
      treated CHO wild-type cells, indicative of C3 cell entry. 

PMID- 27043631
TI  - HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment
      Strategies.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease
      that is the result of tobacco and/or alcohol abuse or infection with high-risk
      Human papillomaviruses. Despite the fact that HPV positive HNSCC cancers form a
      distinct clinical entity with better treatment outcome, all HNSCC are currently
      treated uniformly with the same treatment modality. At present, biologic basis of
      these different outcomes and their therapeutic influence are areas of intense
      investigation. In this review, we will summarize the molecular basis for this
      different outcome, novel treatment opportunities and possible biomarkers for HPV
      positive HNSCC. In particular, the focus will be on several molecular targeted
      strategies that can improve the chemoradiation response by influencing DNA repair
      mechanisms. 

PMID- 27043633
TI  - Computed Tomography Demonstration of the Production and Distribution of Oxygen
      Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for
      Patients with Breast Cancer-Is Intratumoral Injection Not an Ideal Approach to
      Solve the Major Problem of Tumor Hypoxia in Radiotherapy?
AB  - We previously developed a new enzyme-targeting radiosensitization treatment named
      Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II),
      which contains hydrogen peroxide and sodium hyaluronate for injection into
      various types of tumors. For breast cancer treatment, the radiosensitization
      agent was injected into the tumor tissue twice a week under ultrasonographic
      guidance, immediately prior to each administration of radiation therapy. At
      approximately three hours after the second or third injection, computed
      tomography (CT) was performed to confirm the production and distribution of
      oxygen gas generated from the KORTUC radiosensitization agent by catalysis of
      peroxidases contained mainly in tumor tissue. The purpose of this study was to
      demonstrate that tumor hypoxia could be overcome by such a procedure and to
      evaluate the method of intratumoral injection in terms of confirming oxygen
      distribution in the target tumor tissue and around the tumor to be visualized on
      dedicated CT imaging. Three-dimensional reconstructed maximum intensity
      projection imaging of contrast-enhanced breast magnetic resonance imaging was
      used to compare the position of the tumor and that of the generated oxygen.
      Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10
      patients examined in the study. A region of oxygen gas was measured as an average
      value of -457.2 Hounsfield units (HU) as a region of interest. A slightly
      increased HU value compared to the density of air or oxygen was considered due to
      the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed
      CT imaging. The results of this study showed that intratumoral oxygen was
      successfully produced by intratumoral KORTUC injection under ultrasonographic
      guidance, and that tumor hypoxia, which is considered a main cause of
      radioresistance in currently used Linac (linear accelerator) radiation therapy
      for malignant neoplasms, could be resolved by this method. 

PMID- 27043632
TI  - Radioresistance of Brain Tumors.
AB  - Radiation therapy (RT) is frequently used as part of the standard of care
      treatment of the majority of brain tumors. The efficacy of RT is limited by
      radioresistance and by normal tissue radiation tolerance. This is highlighted in
      pediatric brain tumors where the use of radiation is limited by the excessive
      toxicity to the developing brain. For these reasons, radiosensitization of tumor
      cells would be beneficial. In this review, we focus on radioresistance mechanisms
      intrinsic to tumor cells. We also evaluate existing approaches to induce
      radiosensitization and explore future avenues of investigation. 

PMID- 27043634
TI  - Roles of NF-kappaB in Cancer and Inflammatory Diseases and Their Therapeutic
      Approaches.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a crucial
      role in various biological processes, including immune response, inflammation,
      cell growth and survival, and development. NF-kappaB is critical for human
      health, and aberrant NF-kappaB activation contributes to development of various
      autoimmune, inflammatory and malignant disorders including rheumatoid arthritis,
      atherosclerosis, inflammatory bowel diseases, multiple sclerosis and malignant
      tumors. Thus, inhibiting NF-kappaB signaling has potential therapeutic
      applications in cancer and inflammatory diseases. 

PMID- 27043635
TI  - Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth.
AB  - It is still uncertain how the first minimal cellular systems evolved to the
      complexity required for life to begin, but it is obvious that the role of
      amphiphilic compounds in the origin of life is one of huge relevance. Over the
      last four decades a number of studies have demonstrated how amphiphilic molecules
      can be synthesized under plausibly prebiotic conditions. The majority of these
      experiments also gave evidence for the ability of so formed amphiphiles to
      assemble in closed membranes of vesicles that, in principle, could have
      compartmented first biological processes on early Earth, including the emergence
      of self-replicating systems. For a competitive selection of the best performing
      molecular replicators to become operative, some kind of bounded units capable of
      harboring them are indispensable. Without the competition between dynamic
      populations of different compartments, life itself could not be distinguished
      from an otherwise disparate array or network of molecular interactions. In this
      review, we describe experiments that demonstrate how different prebiotically
      available building blocks can become precursors of phospholipids that form
      vesicles. We discuss the experimental conditions that resemble plausibly those of
      the early Earth (or elsewhere) and consider the analytical methods that were used
      to characterize synthetic products. Two brief sections focus on phosphorylating
      agents, catalysts and coupling agents with particular attention given to their
      geochemical context. In Section 5, we describe how condensing agents such as
      cyanamide and urea can promote the abiotic synthesis of phospholipids. We
      conclude the review by reflecting on future studies of phospholipid compartments,
      particularly, on evolvable chemical systems that include giant vesicles composed
      of different lipidic amphiphiles. 

PMID- 27043636
TI  - The Role of Autophagy-Related Proteins in Candida albicans Infections.
AB  - Autophagy plays an important role in maintaining cell homeostasis by providing
      nutrients during periods of starvation and removing damaged organelles from the
      cytoplasm. A marker in the autophagic process is the reversible conjugation of
      LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently,
      a role for LC3 in the elimination of pathogenic bacteria and fungi, including
      Candida albicans (C. albicans), was demonstrated, but these organisms reside in
      single membrane phagosomes. This process is distinct from autophagy and is termed
      LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP
      that distinguish it from classical autophagy and review the role of autophagy
      proteins in host response to C. albicans and other pathogenic fungi. 

PMID- 27043637
TI  - Propofol-Induced Neurotoxicity in the Fetal Animal Brain and Developments in
      Modifying These Effects-An Updated Review of Propofol Fetal Exposure in
      Laboratory Animal Studies.
AB  - In the past twenty years, evidence of neurotoxicity in the developing brain in
      animal studies from exposure to several general anesthetics has been
      accumulating. Propofol, a commonly used general anesthetic medication,
      administered during synaptogenesis, may trigger widespread apoptotic
      neurodegeneration in the developing brain and long-term neurobehavioral
      disturbances in both rodents and non-human primates. Despite the growing evidence
      of the potential neurotoxicity of different anesthetic agents in animal studies,
      there is no concrete evidence that humans may be similarly affected. However,
      given the growing evidence of the neurotoxic effects of anesthetics in laboratory
      studies, it is prudent to further investigate the mechanisms causing these
      effects and potential ways to mitigate them. Here, we review multiple studies
      that investigate the effects of in utero propofol exposure and the developmental
      agents that may modify these deleterious effects. 

PMID- 27043638
TI  - Gelatine-Based Antioxidant Packaging Containing Caesalpinia decapetala and Tara
      as a Coating for Ground Beef Patties.
AB  - The development of antioxidant-active packaging has numerous advantages, such as
      the reduction of synthetic additives in food, the reduction of plastic waste and
      food protection against oxidation reactions. Different concentrations of extracts
      of the plants Caesalpinia decapetala (CD) and Caesalpinia spinosa "Tara" (CS)
      were incorporated into gelatine films as natural antioxidants. The physical,
      mechanical and antioxidant properties of these films were studied. Films
      containing plant extracts at a high concentration had lower tensile strength with
      higher elongation at break points, compared to the control film (p < 0.05). Films
      exhibited antioxidant activity in the oxygen radical absorbance capacity (ORAC)
      and Trolox equivalence antioxidant capacity (TEAC) assays when added at 0.2%. The
      application of gelatine film containing CD and CS was found to be effective in
      delaying lipid oxidation and deterioration of beef patty quality during storage.
      Therefore, the films prepared in this study offered an alternative edible coating
      for the preservation of fresh food. 

PMID- 27043639
TI  - Study of the Properties of Bearberry Leaf Extract as a Natural Antioxidant in
      Model Foods.
AB  - The common bearberry (Arctostaphylos uva-ursi L. Sprengel) is a ubiquitous
      procumbent evergreen shrub located throughout North America, Asia, and Europe.
      The fruits are almost tasteless but the plant contains a high concentration of
      active ingredients. The antioxidant activity of bearberry leaf extract in the
      2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation
      assay was 90.42 mmol Trolox equivalents/g dry weight (DW). The scavenging ability
      of the methanol extract of bearberry leaves against methoxy radicals generated in
      the Fenton reaction was measured via electron paramagnetic resonance. Lipid
      oxidation was retarded in an oil-water emulsion by adding 1 g/kg lyophilised
      bearberry leaf extract. Also, 1 g/kg of lyophilised bearberry leaf extract
      incorporated into a gelatin-based film displayed high antioxidant activity to
      retard the degradation of lipids in muscle foods. The present results indicate
      the potential of bearberry leaf extract for use as a natural food antioxidant. 

PMID- 27043641
TI  - Vaccine Delivery Methods into the Future.
AB  - Several modes of vaccine delivery have been developed in the last 25 years, which
      induce strong immune responses in pre-clinical models and in human clinical
      trials. Some modes of delivery include, adjuvants (aluminum hydroxide, Ribi
      formulation, QS21), liposomes, nanoparticles, virus like particles,
      immunostimulatory complexes (ISCOMs), dendrimers, viral vectors, DNA delivery via
      gene gun, electroporation or Biojector 2000, cell penetrating peptides, dendritic
      cell receptor targeting, toll-like receptors, chemokine receptors and bacterial
      toxins. There is an enormous amount of information and vaccine delivery methods
      available for guiding vaccine and immunotherapeutics development against
      diseases. 

PMID- 27043640
TI  - Direct Delivery of Antigens to Dendritic Cells via Antibodies Specific for
      Endocytic Receptors as a Promising Strategy for Future Therapies.
AB  - Dendritic cells (DCs) are the most potent professional antigen presenting cells
      and are therefore indispensable for the control of immunity. The technique of
      antibody mediated antigen targeting to DC subsets has been the basis of intense
      research for more than a decade. Many murine studies have utilized this approach
      of antigen delivery to various kinds of endocytic receptors of DCs both in vitro
      and in vivo. Today, it is widely accepted that different DC subsets are important
      for the induction of select immune responses. Nevertheless, many questions still
      remain to be answered, such as the actual influence of the targeted receptor on
      the initiation of the immune response to the delivered antigen. Further efforts
      to better understand the induction of antigen-specific immune responses will
      support the transfer of this knowledge into novel treatment strategies for human
      diseases. In this review, we will discuss the state-of-the-art aspects of the
      basic principles of antibody mediated antigen targeting approaches. A table will
      also provide a broad overview of the latest studies using antigen targeting
      including addressed DC subset, targeted receptors, outcome, and applied coupling
      techniques. 

PMID- 27043643
TI  - Considering Exosomal miR-21 as a Biomarker for Cancer.
AB  - Cancer is a fatal human disease. Early diagnosis of cancer is the most effective
      method to prevent cancer development and to achieve higher survival rates for
      patients. Many traditional diagnostic methods for cancer are still not sufficient
      for early, more convenient and accurate, and noninvasive diagnosis. Recently, the
      use of microRNAs (miRNAs), such as exosomal microRNA-21(miR-21), as potential
      biomarkers was widely reported. This initial systematic review analyzes the
      potential role of exosomal miR-21 as a general biomarker for cancers. A total of
      10 studies involving 318 patients and 215 healthy controls have covered 10 types
      of cancers. The sensitivity and specificity of pooled studies were 75% (0.70
      0.80) and 85% (0.81-0.91), with their 95% confidence intervals (CIs), while the
      area under the summary receiver operating characteristic curve (AUC) was 0.93.
      Additionally, we examined and evaluated almost all other issues about biomarkers,
      including cutoff points, internal controls and detection methods, from the
      literature. This initial meta-analysis indicates that exosomal miR-21 has a
      strong potential to be used as a universal biomarker to identify cancers,
      although as a general biomarker the case number for each cancer type is small.
      Based on the literature, a combination of miRNA panels and other cancer antigens,
      as well as a selection of appropriate internal controls, has the potential to
      serve as a more sensitive and accurate cancer diagnosis tool. Additional
      information on miR-21 would further support its use as a biomarker in cancer. 

PMID- 27043642
TI  - Signal Transduction Pathways of EMT Induced by TGF-beta, SHH, and WNT and Their
      Crosstalks.
AB  - Epithelial-to-mesenchymal transition (EMT) is a key step in development, wound
      healing, and cancer development. It involves cooperation of signaling pathways,
      such as transformation growth factor-beta (TGF-beta), Sonic Hedgehog (SHH), and
      WNT pathways. These signaling pathways crosstalk to each other and converge to
      key transcription factors (e.g., SNAIL1) to initialize and maintain the process
      of EMT. The functional roles of multi-signaling pathway crosstalks in EMT are
      sophisticated and, thus, remain to be explored. In this review, we focused on
      three major signal transduction pathways that promote or regulate EMT in
      carcinoma. We discussed the network structures, and provided a brief overview of
      the current therapy strategies and drug development targeted to these three
      signal transduction pathways. Finally, we highlighted systems biology approaches
      that can accelerate the process of deconstructing complex networks and drug
      discovery. 

PMID- 27043644
TI  - Measurement of Rapid Amiloride-Dependent pH Changes at the Cell Surface Using a
      Proton-Sensitive Field-Effect Transistor.
AB  - We present a novel method for the rapid measurement of pH fluxes at close
      proximity to the surface of the plasma membrane in mammalian cells using an ion
      sensitive field-effect transistor (ISFET). In conjuction with an efficient
      continuous superfusion system, the ISFET sensor was capable of recording rapid
      changes in pH at the cells' surface induced by intervals of ammonia loading and
      unloading, even when using highly buffered solutions. Furthermore, the system was
      able to isolate physiologically relevant signals by not only detecting the
      transients caused by ammonia loading and unloading, but display steady-state
      signals as would be expected by a proton transport-mediated influence on the
      extracellular proton-gradient. Proof of concept was demonstrated through the use
      of 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a small molecule inhibitor of
      sodium/hydrogen exchangers (NHE). As the primary transporter responsible for
      proton balance during cellular regulation of pH, non-electrogenic NHE transport
      is notoriously difficult to detect with traditional methods. Using the NHE
      positive cell lines, Chinese hamster ovary (CHO) cells and NHE3-reconstituted
      mouse skin fibroblasts (MSF), the sensor exhibited a significant response to EIPA
      inhibition, whereas NHE-deficient MSF cells were unaffected by application of the
      inhibitor. 

PMID- 27043645
TI  - Differentiation of Crohn's Disease-Associated Isolates from Other Pathogenic
      Escherichia coli by Fimbrial Adhesion under Shear Force.
AB  - Shear force exerted on uropathogenic Escherichia coli adhering to surfaces makes
      type-1 fimbriae stretch out like springs to catch on to mannosidic receptors.
      This mechanism is initiated by a disruption of the quaternary interactions
      between the lectin and the pilin of the two-domain FimH adhesin and transduces
      allosterically to the mannose-binding pocket of FimH to increase its affinity.
      Mannose-specific adhesion of 14 E. coli pathovars was measured under flow, using
      surface plasmon resonance detection on functionalized graphene-coated gold
      interfaces. Increasing the shear had important differential consequences on
      bacterial adhesion. Adherent-invasive E. coli, isolated from the feces and
      biopsies of Crohn's disease patients, consistently changed their adhesion
      behavior less under shear and displayed lower SPR signals, compared to E. coli
      opportunistically infecting the urinary tract, intestines or loci of knee and hip
      prostheses. We exemplified this further with the extreme behaviors of the
      reference strains UTI89 and LF82. Whereas their FimA major pilins have identical
      sequences, FimH of LF82 E. coli is marked by the Thr158Pro mutation. Positioned
      in the inter-domain region known to carry hot spots of mutations in E. coli
      pathotypes, residue 158 is indicated to play a structural role in the allosteric
      regulation of type-1 fimbriae-mediated bacterial adhesion. 

PMID- 27043646
TI  - The Involvement of Acetaldehyde in Ethanol-Induced Cell Cycle Impairment.
AB  - BACKGROUND: Hepatocytes metabolize the vast majority of ingested ethanol. This
      metabolic activity results in hepatic toxicity and impairs the ability of
      hepatocytes to replicate. Previous work by our group has shown that ethanol
      metabolism results in a G2/M cell cycle arrest. The intent of these studies was
      to discern the roles of acetaldehyde and reactive oxygen, two of the major by
      products of ethanol metabolism, in the G2/M cell cycle arrest. METHODS: To
      investigate the role of ethanol metabolites in the cell cycle arrest, VA-13 and
      VL-17A cells were used. These are recombinant Hep G2 cells that express alcohol
      dehydrogenase or alcohol dehydrogenase and cytochrome P450 2E1, respectively.
      Cells were cultured with or without ethanol, lacking or containing the
      antioxidants N-acetylcysteine (NAC) or trolox, for three days. Cellular
      accumulation was monitored by the DNA content of the cultures. The accumulation
      of the cyclin-dependent kinase, Cdc2 in the inactive phosphorylated form (p-Cdc2)
      and the cyclin-dependent kinase inhibitor p21 were determined by immunoblot
      analysis. RESULTS: Cultures maintained in the presence of ethanol demonstrated a
      G2/M cell cycle arrest that was associated with a reduction in DNA content and
      increased levels of p-Cdc2 and p21, compared with cells cultured in its absence.
      Inclusion of antioxidants in the ethanol containing media was unable to rescue
      the cells from the cell cycle arrest or these ethanol metabolism-mediated
      effects. Additionally, culturing the cells in the presence of acetaldehyde alone
      resulted in increased levels of p-Cdc2 and p21. CONCLUSIONS: Acetaldehyde
      produced during ethanol oxidation has a major role in the ethanol metabolism
      mediated G2/M cell cycle arrest, and the concurrent accumulation of p21 and p
      Cdc2. Although reactive oxygen species are thought to have a significant role in
      ethanol-induced hepatocellular damage, they may have a less important role in the
      inability of hepatocytes to replace dead or damaged cells.

PMID- 27043647
TI  - Trying on tRNA for Size: RNase P and the T-box Riboswitch as Molecular Rulers.
AB  - Length determination is a fundamental problem in biology and chemistry. Numerous
      proteins measure distances on linear biopolymers to exert effects with remarkable
      spatial precision. Recently, ruler-like devices made of noncoding RNAs have been
      structurally and biochemically characterized. Two prominent examples are the
      RNase P ribozyme and the T-box riboswitch. Both act as molecular calipers. The
      two RNAs clamp onto the elbow of tRNA (or pre-tRNA) and make distance
      measurements orthogonal to each other. Here, we compare and contrast the
      molecular ruler characteristics of these RNAs. RNase P appears pre-configured to
      measure a fixed distance on pre-tRNA to ensure the fidelity of its maturation.
      RNase P is a multiple-turnover ribozyme, and its rigid structure efficiently
      selects pre-tRNAs, cleaves, and releases them. In contrast, the T-box is flexible
      and segmented, an architecture that adapts to the intrinsically flexible tRNA.
      The tripartite T-box inspects the overall shape, anticodon sequence, and
      aminoacylation status of an incoming tRNA while it folds co-transcriptionally,
      leading to a singular, conditional genetic switching event. The elucidation of
      the structures and mechanisms of action of these two RNA molecular rulers may
      augur the discovery of new RNA measuring devices in noncoding and viral
      transcriptomes, and inform the design of artificial RNA rulers. 

PMID- 27043649
TI  - Perceptual Anchors and the Dispersion of Nasality Ratings.
AB  - OBJECTIVE: This investigation studied the effects of perceptual anchors on the
      dispersion and reliability of listener ratings of nasality. DESIGN: Listeners (N
      = 129) were assigned to one of six listening groups. Each group rated nasality
      independently for 100 speech samples on a seven-point scale that ranged from 1 =
      normal nasality to 7 = severe hypernasality. The anchors used were examples of a
      1, 3, 4, 5, and/or 7 on the rating scale. These anchors were played selectively
      to group 2 (4), group 3 (1 and 7), group 4 (3 and 5), group 5 (1, 4, 7), and
      group 6 (7). Group 1 had no anchor. PARTICIPANTS: Of the speakers, 95 were
      children followed by a craniofacial team and five were children without histories
      of speech disorders. MAIN OUTCOME MEASURES: The outcome measures were 12,900
      ratings of nasality on a seven-point scale. RESULTS: Q values showed that group
      5, which was the only group to receive three anchors, had the lowest, or best, Q
      value (0.78), and group 1 (no anchor) had the highest, or worst, Q value (0.99).
      Across groups, the most reliable ratings were those at scale values 1 (Q = 0.46)
      and 7 (Q = 0.56). The least reliable ratings were at scale values 3 (Q = 1.01), 4
      (Q = 1.03), and 5 (Q = 1.06). CONCLUSIONS: Nasality rating reliability/dispersion
      was influenced by the presence and location of anchor stimuli. Consistent with
      absolute judgment theory, nasality ratings showed a strong end effect.

PMID- 27043648
TI  - Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in
      Florida, Massachusetts, and Michigan, 2000-2010.
AB  - IMPORTANCE: Use of assisted reproductive technology (ART) has been associated
      with increased risks for birth defects. Variations in birth defect risks
      according to type of ART procedure have been noted, but findings are
      inconsistent. OBJECTIVES: To examine the prevalence of birth defects among
      liveborn infants conceived with and without ART and to evaluate risks associated
      with certain ART procedures among ART-conceived infants. DESIGN, SETTING, AND
      PARTICIPANTS: Used linked ART surveillance, birth certificates, and birth defects
      registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for
      ascertaining birth defect cases varied by state. Resident live births during 2000
      to 2010 were included, and the analysis was conducted between Feburary 2015 and
      August 2015. EXPOSURES: Use of ART among all live births and use of certain ART
      procedures among ART births. MAIN OUTCOME AND MEASURES: Prevalence of selected
      chromosomal and nonchromosomal birth defects that are usually diagnosed at or
      immediately after birth. RESULTS: Of the 4 618 076 liveborn infants between 2000
      and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or
      more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants
      (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association
      remained significant after adjusting for maternal characteristics and year of
      birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences
      were observed for singleton ART births vs their non-ART counterparts (63.69 per
      10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59).
      Among multiple births, the prevalence of rectal and large intestinal
      atresia/stenosis was higher for ART births compared with non-ART births (aRR,
      2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer,
      infants born to mothers with ovulation disorders had a higher prevalence of
      nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to
      mothers without the diagnosis, and use of assisted hatching was associated with
      birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity
      adjusted P values for these associations were greater than .05. CONCLUSIONS AND
      RELEVANCE: Infants conceived after ART had a higher prevalence of certain birth
      defects. Assisted hatching and diagnosis of ovulation disorder were marginally
      associated with increased risks for nonchromosomal birth defects; however, these
      associations may be caused by other underlying factors.

PMID- 27043650
TI  - Neurological Development of Children With Isolated Robin Sequence Treated With
      Nasopharyngeal Intubation in Early Infancy.
AB  - The study assessed the neurodevelopment of children with isolated Robin sequence
      (IRS) and evaluated if children treated exclusively with nasopharyngeal
      intubation (NPI) present delay in neurological development. The prospective and
      cross-sectional study was conducted at the Hospital for Rehabilitation of
      Craniofacial Anomalies, Brazil. Children with IRS were divided into two groups
      according to the type of treatment in early infancy: 38 were treated with NPI
      (more severe cases) and 24 with postural treatment (less severe cases). Regarding
      interventions, children were assessed at 2 to 6 years of age using the Denver II
      Developmental Screening Test (Denver II) and Neurological Evolutionary
      Examination (NEE). According to Denver II, 73.7% in the NPI group and 79.2% in
      the postural group presented normal development. This result was similar to the
      results of different studies in the literature with typical population.
      Considering all areas of development, there were no significant differences in
      Denver II between the NPI and postural groups (P = .854). In the NPI group, 89.5%
      of children and 87.5% in the postural group presented normal development in NEE.
      Language was the most affected area, as 18.4% and 20.8% of children in NPI and
      postural group, respectively, presented risk for delay in the Denver II. The
      increased risk for delay in language area was probably due to anatomical
      conditions of the muscles involved in speech, and to hearing oscillations, as
      47.4% in NPI group and 58.3% in postural group underwent myringotomy. IRS treated
      with NPI had neurological development similar to those in less severe cases.
      Children treated exclusively with NPI did not present delay in neurological
      development.

PMID- 27043651
TI  - Influence of Standardized Orientation on Patient Perception of Perioperative Care
      Following Alveolar Cleft Repair: A Survey Based Study of Patients Treated in a
      Large Academic Medical Center.
AB  - OBJECTIVE: This study aims to better understand patient-reported outcomes for
      iliac bone grafting surgery for alveolar cleft repair and to determine how
      standardizing perioperative patient instruction affects patient-reported
      outcomes. DESIGN: Retrospective survey-based assessment of patients undergoing
      iliac bone grafting with and without hospital-based systems standardization.
      SETTING: Academic tertiary care hospital. PATIENTS: Of the 195 identified
      patients, 127 participated. INTERVENTIONS: Survey on pain and satisfaction
      regarding iliac bone grafting surgery. MAIN OUTCOME MEASURES: Survey answers
      measured patient opinions about the surgery. Answers of the pre- and
      poststandardization patients were compared to determine the effect of
      standardizing patient instructions. RESULTS: Patients rated their satisfaction
      with the surgery and recovery a 4.5 and 4.4 out of 5, respectively. They rated
      their overall pain in the hospital a 5.5 out of 10 (4.9 in the mouth, 5.7 in the
      hip). Patients were discharged an average of 1.2 days after surgery and could
      return to normal daily activity in 6.1 days. Poststandardization patients were
      more likely to adhere to instructions regarding use of an antibacterial
      mouthrinse and a protective oral splint. CONCLUSIONS: Patients were highly
      satisfied with the iliac bone grafting procedure and the recovery and reported
      only moderate levels of postoperative pain. Implementing standardized patient
      instructions may not affect patient satisfaction or pain severity, but it
      significantly increased patient adherence to physician instructions.

PMID- 27043652
TI  - Oral Clefts and Academic Performance in Adolescence: The Impact of Anesthesia
      Related Neurotoxicity, Timing of Surgery, and Type of Oral Clefts.
AB  - OBJECTIVE: Early life exposure to anesthesia and surgery is suspected to
      associate with cognitive impairment later in life. We compared academic
      achievement among adolescents with cleft lip only (CL), cleft palate only (CP),
      and cleft lip and cleft palate (CLP) with a noncleft control group to investigate
      whether outcome depends on timing and number of operations during childhood
      and/or type of oral cleft. DESIGN: Nationwide register-based follow-up study.
      SETTING: Danish birth cohort 1986 to 1990. PARTICIPANTS: Five hundred fifty-eight
      children with isolated CL (n = 171), CLP (n = 222), or CP (n = 195), of which 509
      children had been exposed to anesthesia and one or more cleft operation(s), and a
      5% sample of the birth cohort (n = 14,677). MAIN OUTCOME MEASURE(S): Test score
      in the Danish standardized ninth-grade exam and proportion of nonattainment,
      defined as "results for ninth-grade exam unavailable." Data adjusted for sex,
      birth weight, parental age, and parental level of education. RESULTS: Compared to
      controls, children with CL achieved higher scores (mean difference 0.12, 95% CI 
      0.05; 0.29) and children with CLP presented with lower scores (mean difference 
      0.06, 95% CI -0.21; 0.09), albeit both statistically insignificant. Children with
      CP achieved significantly lower scores, mean difference -0.20 (95% CI -0.38; 
      0.03). Odds ratios for nonattainment at final exam were: CL 0.79 (95% CI 0.46;
      1.35), CLP 1.07 (95% CI 0.71; 1.61), CP 2.59 (95% CI 1.78; 3.76). CONCLUSIONS:
      Oral cleft type rather than number and timing of anesthesia and operations
      associate to poorer academic performance. Although a potential neurotoxic effect
      due to anesthetic agents is not reflected in the data, it cannot be completely
      excluded.

PMID- 27043653
TI  - Computed Tomographic Estimation of Particulate Cancellous Bone and Marrow Weight
      for Successful Transplant in Unilateral Cleft Lip and Palate Patients.
AB  - OBJECTIVE: The defect volume measured on computed tomography (CT) for secondary
      bone graft (SBG) is well correlated to the actual amount of particulate
      cancellous bone and marrow (PCBM) transplanted in unilateral cleft lip and palate
      (UCLP) patients. However, the validity of such measurements have not been
      completely verified due to lack of evaluation of treatment results. The objective
      of this study was to propose an estimation method by CT based on the data of
      successfully treated patients. For this purpose, the association was initially
      verified between the weight of transplanted PCBM and the defect volume measured
      on CT using the results of successfully treated patients. METHODS: Treatment
      results were evaluated 1 year after SBG by intraoral radiography in 50 UCLP
      patients. For the patients with good results, the correlation was investigated
      between the defect volume on CT and the transplanted PCBM weight, and a method
      was proposed based on PCBM density, calculated as PCBM weight divided by defect
      volume on CT. RESULTS: In successfully treated patients showing level 3 or 4
      alveolar resorption, a strong correlation (r = .87) was found between the volume
      on CT and the PCBM weight. Level 4 results were observed in 22 of 23 (95.7%)
      patients who had calculated PCBM densities of more than 6 g/cm3. CONCLUSIONS:
      Volume estimation on preoperative CT was confirmed to have sufficient validity.
      The weight of PCBM transplanted should be greater than the defect volume on CT
      multiplied by 6.

PMID- 27043654
TI  - Breast Milk Feeding Rates in Patients With Cleft Lip and Palate at a North
      American Craniofacial Center.
AB  - OBJECTIVE: Our study goal was to evaluate the rates of breast milk feeding among
      patients with oral clefts at a large North American Craniofacial Center. METHODS:
      Parents of patients with oral clefts born from 2000 to 2012 and treated at our
      center were interviewed regarding cleft diagnosis, counseling received for
      feeding, and feeding habits. RESULTS: Data were obtained from parents of 110
      patients with oral clefts. Eighty-four percent of parents received counseling for
      feeding a child with a cleft. Sixty-seven percent of patients received breast
      milk for some period of time with a mean duration of 5.3 months (range 0.25 to 18
      months). When used, breast milk constituted the majority of the diet with a mean
      percentage of 75%. Breast milk feeding rates increased successively over the 13
      year study period. The most common method of providing breast milk was the
      Haberman feeder at 75% with other specialty cleft bottles composing an additional
      11%. Parents who received counseling were more likely to give breast milk to
      their infant (P = .02). Duration of NasoAlveolar Molding prior to cleft lip
      repair did not affect breast milk feeding length (P = .72). Relative to patients
      with cleft lip and palate, patients with isolated cleft lip had a breast milk
      feeding odds ratio of 1.71. CONCLUSION: We present breast milk feeding in the
      North American cleft population. Although still lower than the noncleft
      population, breast milk feeding with regards to initiation rate, length of time,
      and proportion of total diet is significantly higher than previously reported.

PMID- 27043655
TI  - JOURNAL CLUB: Identification of Bone Metastasis With Routine Prostate MRI: A
      Study of Patients With Newly Diagnosed Prostate Cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether routine prostate MRI
      is adequate for detection of bone metastasis in patients with newly diagnosed
      prostate cancer. MATERIALS AND METHODS: The study included 308 patients with
      newly diagnosed prostate cancer who underwent prostate MRI. Two radiologists
      categorized MRI findings as normal, metastasis, or equivocal. Histologic analysis
      or best valuable comparator based on comprehensive review of images and clinical
      follow-up studies were used as reference standards. Clinicopathologic variables
      and MRI findings were compared between patients with and those without bone
      metastasis by use of chi-square and t tests. The diagnostic performance of
      prostate MRI for detecting bone metastasis was assessed by ROC analysis. Subgroup
      analysis was performed for patients at high risk of bone metastasis. RESULTS:
      Twenty-one (6.8%) patients had bone metastasis. They had significantly higher
      prostate-specific antigen levels (p = 0.015) and Gleason scores (p < 0.001) than
      those without bone metastasis. The diagnostic performance of MRI was as follows:
      sensitivity, 95.2%; specificity, 99-100%; positive predictive value, 86.9-100%;
      negative predictive value, 99.7%. For 119 patients at high risk of bone
      metastasis, these values were 95%, 100%, 100%, and 99%. Only 1 of the 21 (4.8%)
      patients had bone metastasis only in an area not explored with prostate MRI, that
      is, the thoracic spine. CONCLUSION: The diagnostic performance of routine
      prostate MRI for identifying bone metastasis in patients with newly diagnosed
      prostate cancer was excellent.

PMID- 27043656
TI  - Tandem Rh-catalysis: decarboxylative beta-keto acid and alkyne cross-coupling.
AB  - Herein, we describe a regioselective Rh-catalyzed decarboxylative cross-coupling
      of beta-keto acids and alkynes to access branched gamma,delta-unsaturated
      ketones. Rh-hydride catalysis enables the isomerization of an alkyne to generate
      a metal-allyl species that can undergo carbon-carbon bond formation. Ketones are
      generated under mild conditions, without the need for base or activated
      electrophiles. 

PMID- 27043657
TI  - Bioresorbable Vascular Scaffolds in Coronary Artery Disease: Weighing the
      Evidence and Next Steps.

PMID- 27043658
TI  - CD55 is a HIF-2alpha marker with anti-adhesive and pro-invading properties in
      neuroblastoma.
AB  - CD55 has been revealed to have an important role in tumor genesis, and presence
      of small populations of cells with strong CD55 expression would be sufficient to
      predict poor prognosis of several tumors. In our study we revealed that CD55 is a
      novel target of hypoxia-inducible factor HIF-2alpha in neuroblastoma (NB) cells.
      We show that HIF-2alpha expression is sufficient to sustain stem-like features of
      NB cells, whereas CD55 protein upon HIF-2alpha expression contributes to growth
      of colonies and to invasion of cells, but not to stemness features.
      Interestingly, in NB tissues, CD55 expression is limited to quite a small
      population of cells that are HIF-2alpha positive, and the gene expression of CD55
      in the NB data set reveals that the presence of CD55(high) affects prognosis of
      NB patients. The functional characterization of CD55-positive populations within
      heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti
      adhesive properties that might provide the basis for the ability of solid tumors
      to survive as microscopic residual disease. The easy accessibility to CD55
      membrane antigen will offer the possibility of a novel antibody approach in the
      treatment of recurrent tumors and will provide a ready target for antibody-based
      visualization in NB diagnosis and prognosis. 

PMID- 27043659
TI  - Ultraconserved region-containing Transformer 2beta4 controls senescence of colon
      cancer cells.
AB  - Ultraconserved regions (UCRs) are >200 bp genomic segments with perfect human-to
      rodent sequence identity. Transcribed UCRs constitute a new category of noncoding
      RNAs whose functions remain poorly understood. The human transformer 2beta
      (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring
      introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing
      splice variant (TRA2beta4) was expressed preferentially in the nuclei of human
      colon cancer cells. TRA2beta4 knockdown p53-independently stimulated CDKN1A
      transcription and increased p21, resulting in the appearance of senescent cells.
      Biotin pull-down and RNA immunoprecipitation assays revealed that TRA2beta4
      interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop
      structure of exon 2. Mutation of this sequence (485-AAGG-488) disrupted the stem
      loop structure, blocked the interaction with Sp1 and increased CDKN1A
      transcription. Overexpression of TRA2beta4 significantly decreased CDKN1A mRNA
      levels and accelerated cell growth, but the introduction of the mutation in the
      Sp1-binding sequence completely canceled these effects. Taken together, TRA2beta4
      may sequester Sp1 from occupying promoters of target genes including CDKN1A,
      promoting cell growth by interrupting the senescence-related gene expression
      program. This novel function of TRA2beta4 may uncover an oncogenic function of
      transcribed UCRs. 

PMID- 27043660
TI  - BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation
      and epigenetic silencing through targeting EZH2 in breast cancer.
AB  - BRCA1 mutation or depletion correlates with basal-like phenotype and poor
      prognosis in breast cancer but the underlying reason remains elusive. RNA and
      protein analysis of a panel of breast cancer cell lines revealed that BRCA1
      deficiency is associated with downregulation of the expression of the pleiotropic
      tumour suppressor FOXO3. Knockdown of BRCA1 by small interfering RNA (siRNA)
      resulted in downregulation of FOXO3 expression in the BRCA1-competent MCF-7,
      whereas expression of BRCA1 restored FOXO3 expression in BRCA1-defective HCC70
      and MDA-MB-468 cells, suggesting a role of BRCA1 in the control of FOXO3
      expression. Treatment of HCC70 and MDA-MB-468 cells with either the DNA
      methylation inhibitor 5-aza-2'-deoxycitydine, the N-methyltransferase enhancer of
      zeste homologue 2 (EZH2) inhibitor GSK126 or EZH2 siRNA induced FOXO3 mRNA and
      protein expression, but had no effect on the BRCA1-competent MCF-7 cells.
      Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2,
      DNMT1/3a/b and histone H3 lysine 27 trimethylation (H3K27me3) are recruited to
      the endogenous FOXO3 promoter, further advocating that these proteins interact to
      modulate FOXO3 methylation and expression. In addition, ChIP results also
      revealed that BRCA1 depletion promoted the recruitment of the DNA
      methyltransferases DNMT1/3a/3b and the enrichment of the EZH2-mediated
      transcriptional repressive epigenetic marks H3K27me3 on the FOXO3 promoter.
      Methylated DNA immunoprecipitation assays also confirmed increased CpG
      methylation of the FOXO3 gene on BRCA1 depletion. Analysis of the global gene
      methylation profiles of a cohort of 33 familial breast tumours revealed that
      FOXO3 promoter methylation is significantly associated with BRCA1 mutation.
      Furthermore, immunohistochemistry further suggested that FOXO3 expression was
      significantly associated with BRCA1 status in EZH2-positive breast cancer.
      Consistently, high FOXO3 and EZH2 mRNA levels were significantly associated with
      good and poor prognosis in breast cancer, respectively. Together, these data
      suggest that BRCA1 can prevent and reverse FOXO3 suppression via inhibiting EZH2
      and, consequently, its ability to recruit the transcriptional repressive H3K27me3
      histone marks and the DNA methylases DNMT1/3a/3b, to induce DNA methylation and
      gene silencing on the FOXO3 promoter. 

PMID- 27043661
TI  - The Bag-1 inhibitor, Thio-2, reverses an atypical 3D morphology driven by Bag-1L
      overexpression in a MCF-10A model of ductal carcinoma in situ.
AB  - Mammary MCF-10A cells seeded on reconstituted basement membrane form spherical
      structures with a hollow central lumen, termed acini, which are a physiologically
      relevant model of mammary morphogenesis. Bcl-2-associated athanogene 1 (Bag-1) is
      a multifunctional protein overexpressed in breast cancer and ductal carcinoma in
      situ. When present in the nucleus Bag-1 is predictive of clinical outcome in
      breast cancer. Bag-1 exists as three main isoforms, which are produced by
      alternative translation initiation from a single mRNA. The long isoform of Bag-1,
      Bag-1L, contains a nuclear localisation sequence not present in the other
      isoforms. When present in the nucleus Bag-1L, but not the other Bag-1 isoforms,
      can interact with and modulate the activities of estrogen-, androgen- and vitamin
      D-receptors. Overexpression of Bag-1 mRNA in MCF-10A is known to produce acini
      with luminal filling reminiscent of ductal carcinoma in situ. As this mRNA
      predominantly overexpresses the short isoform of Bag-1, Bag-1S, we set out to
      examine whether the nuclear Bag-1L isoform is sufficient to drive premalignant
      change by developing a Bag-1L-overexpressing MCF-10A model. Two clones
      differentially overexpressing Bag-1L were grown in two-dimensional (2D) and three
      dimensional (3D) cultures and compared with an established model of HER2-driven
      transformation. In 2D cultures, Bag-1L overexpression reduced proliferation but
      did not affect growth factor responsiveness or clonogenicity. Acini formed by Bag
      1L-overexpressing cells exhibited reduced luminal clearing when compared with
      controls. An abnormal branching morphology was also observed which correlated
      with the level of Bag-1L overexpression, suggesting further malignant change.
      Treatment with Thio-2, a small-molecule inhibitor of Bag-1, reduced the level of
      branching. In summary, 3D cultures of MCF-10A mammary epithelial cells
      overexpressing Bag-1L demonstrate a premalignant phenotype with features of
      ductal carcinoma in situ. Using this model to test the small-molecule Bag-1
      inhibitor, Thio-2, reveals its potential to reverse the atypical branched
      morphology of acini that characterizes this premalignant change. 

PMID- 27043662
TI  - The SMAC mimetic, LCL-161, reduces survival in aggressive MYC-driven lymphoma
      while promoting susceptibility to endotoxic shock.
AB  - Inhibitor of apoptosis proteins (IAPs) antagonize caspase activation and regulate
      death receptor signaling cascades. LCL-161 is a small molecule second
      mitochondrial activator of caspase (SMAC) mimetic, which both disengages IAPs
      from caspases and induces proteasomal degradation of cIAP-1 and -2, resulting in
      altered signaling through the NFkappaB pathway, enhanced TNF production and
      sensitization to apoptosis mediated by the extrinsic pathway. SMAC mimetics are
      undergoing clinical evaluation in a range of hematological malignancies. Burkitt
      like lymphomas are hallmarked by a low apoptotic threshold, conveying sensitivity
      to a range of apoptosis-inducing stimuli. While evaluating LCL-161 in the EMU-Myc
      model of aggressive Burkitt-like lymphoma, we noted unexpected resistance to
      apoptosis induction despite 'on-target' IAP degradation and NFkappaB activation.
      Moreover, LCL-161 treatment of lymphoma-bearing mice resulted in apparent disease
      acceleration concurrent to augmented inflammatory cytokine-release in the same
      animals. Indiscriminate exposure of lymphoma patients to SMAC mimetics may
      therefore be detrimental due to both unanticipated prolymphoma effects and
      increased susceptibility to endotoxic shock. 

PMID- 27043663
TI  - MicroRNA-206 is differentially expressed in Brca1-deficient mice and regulates
      epithelial and stromal cell compartments of the mouse mammary gland.
AB  - Depletion of Brca1 leads to defects in mouse mammary gland development and
      mammary tumors in humans and mice. To explore the role of microRNAs (miRNAs) in
      this process, we examined the mammary glands of MMTV-Cre Brca1(Co/Co) mice for
      differential miRNA expression using a candidate approach. Several miRNAs were
      differentially expressed in mammary tissue at day 1 of lactation and in mammary
      epithelial cell lines in which Brca1 messenger RNA (mRNA) levels have been
      reduced. Functional studies revealed that several of these miRNAs regulate
      mammary epithelial cell function in vitro, including miR-206. Creation and
      analysis of MMTV-miR-206 transgenic mice showed no effect on lactational mammary
      development and no tumors, but indicates a role in mammary tissue remodeling in
      mature mice, potentially involving Igf-1 and Sfrp1. These results indicate the
      potential of miRNAs to mediate the consequences of Brca1 loss and suggest a novel
      function for miR-206. 

PMID- 27043666
TI  - A Child With Septic Shock and Purpura.

PMID- 27043667
TI  - Effect of Icodextrin Solution on the Preservation of Residual Renal Function in
      Peritoneal Dialysis Patients: A Randomized Controlled Study.
AB  - Although icodextrin solution has been highlighted in the fluid management
      compared to glucose-based solutions, proof of a beneficial effect of icodextrin
      solution on residual renal function (RRF) is lacking. We conducted a multicenter
      prospective randomized controlled open-label trial to investigate whether
      icodextrin solution can preserve RRF.One hundred patients with urine volume >=750
      mL/day from 8 centers in Korea were randomly assigned to receive 1 exchange of
      icodextrin solution for a >=8 hour-dwell time and 2 exchanges of 1.5% glucose
      based biocompatible neutral pH solution or 1 exchange of >=2.5% and 2 exchanges
      of 1.5% glucose-based biocompatible solutions. Using mixed-effects general linear
      models, we analyzed changes in residual glomerular filtration rate (GFR) and
      daily urine volume at 1 year.Forty-nine patients were assigned to the icodextrin
      group and 51 to the glucose solution group. During follow-up, the slope of the
      decline in residual GFR was -0.170 mL/min/month/1.73 m2 in the icodextrin group,
      while it was -0.155 mL/min/month/1.73 m2 in the glucose solution group (95%
      confidence interval [CI], -0.06 to 0.10; P = 0.701). Daily urine volume decreased
      faster in the glucose solution group than in the icodextrin group (-31.02 vs 
      11.88 mL per month; 95% CI, -35.85 to -2.44; P = 0.025). Results were consistent
      when we analyzed using intention-to-treat and per protocol principles. There were
      no differences in fluid status, peritoneal ultrafiltration, and peritoneal
      transport between groups during follow-up.This study clearly showed that
      icodextrin solution preserves residual urine volume better than glucose solution.

PMID- 27043668
TI  - Variable Solitary Fibrous Tumor Locations: CT and MR Imaging Features.
AB  - The aim of the study is to describe the radiological imaging features of
      different solitary fibrous tumors (SFTs) locations and present histopathological
      correlations. From 2007 to 2013, 20 cases of histologically confirmed that SFTs
      were retrospectively analyzed with computed tomography (CT; 9/20), magnetic
      resonance imaging (MRI; 5/20), or both CT and MRI (6/20). All 20 SFTs were well
      defined, lobular, soft-tissue masses, and 60% were located outside of the pleura.
      One pleural case invaded to the 10th thoracic vertebra and had lung metastases.
      Images revealed 11 heterogeneous lesions that exceeded 3.0 +/- 0.203 cm along the
      greatest axis with patchy necrotic foci, and 9 homogeneous lesions <3.0 +/-
      0.203. Microscopically, all SFTs were proliferative spindle cells with varying
      degrees of fibrosis and interspersed vessel branching. Cells were strongly
      immunopositive for CD34. Here we review variable imaging findings of SFTs, which
      can be within the pleura as well as within other serosal tissues such as the
      meninges and postperitoneum. SFTs > 3.0 +/- 0.203 cm along the greatest axis
      appeared to be mixed patterns, whereas SFTs < 3.0 +/- 0.203 cm had isodense
      appearances. SFTs cells were CD34 immunopositive and surgery was a first-line
      treatment choice.

PMID- 27043669
TI  - Morphologic Analysis of the Temporomandibular Joint Between Patients With Facial
      Asymmetry and Asymptomatic Subjects by 2D and 3D Evaluation: A Preliminary Study.
AB  - Signs and symptoms of temporomandibular joint (TMJ) dysfunction are commonly
      found in patients with facial asymmetry. Previous studies on the TMJ position
      have been limited to 2-dimensional (2D) radiographs, computed tomography (CT), or
      cone-beam computed tomography (CBCT). The purpose of this study was to compare
      the differences of TMJ position by using 2D CBCT and 3D model measurement
      methods. In addition, the differences of TMJ positions between patients with
      facial asymmetry and asymptomatic subjects were investigated. We prospectively
      recruited 5 patients (cases, mean age, 24.8 +/- 2.9 years) diagnosed with facial
      asymmetry and 5 asymptomatic subjects (controls, mean age, 26 +/- 1.2 years). The
      TMJ spaces, condylar and ramus angles were assessed by using 2D and 3D methods.
      The 3D models of mandible, maxilla, and teeth were reconstructed with the 3D
      image software. The variables in each group were assessed by t-test and the level
      of significance was 0.05. There was a significant difference in the horizontal
      condylar angle (HCA), coronal condylar angle (CCA), sagittal ramus angle (SRA),
      medial joint space (MJS), lateral joint space (LJS), superior joint space (SJS),
      and anterior joint space (AJS) measured in the 2D CBCT and in the 3D models (P <
      0.05). The case group had significantly smaller SJS compared to the controls on
      both nondeviation side (P = 0.009) and deviation side (P = 0.004). In the case
      group, the nondeviation SRA was significantly larger than the deviation side (P =
      0.009). There was no significant difference in the coronal condylar width (CCW)
      in either group. In addition, the anterior disc displacement (ADD) was more
      likely to occur on the deviated side in the case group. In conclusion, the 3D
      measurement method is more accurate and effective for clinicians to investigate
      the morphology of TMJ than the 2D method.

PMID- 27043670
TI  - Chlamydia Trachomatis Infection-Associated Risk of Cervical Cancer: A Meta
      Analysis.
AB  - As whether Chlamydia trachomatis infection increases the risk of cervical cancer
      is controversial in the literature, we performed a meta-analysis.Based on a
      comprehensive search of publications in the Medline, Cochrane, and EMBASE
      databases, we identified and extracted data from all relevant articles examining
      C. trachomatis infection and the risk of cervical cancer. The quality of each
      included study was assessed according to the 9-star Newcastle-Ottawa scale. The
      strength of association between the C. trachomatis and risk of cervical cancer
      was estimated by odds ratio (OR) and 95% confidence intervals (CIs). This review
      was registered at PROSPERO with registration No. CRD42014015672. A total of 22
      studies with 4291 cervical cancer cases and 7628 controls were identified.
      Overall, C. trachomatis was significantly linked to increased cervical cancer
      risk in prospective studies (OR = 2.21, 95% CI: 1.88-2.61, P < 0.001), as well as
      in retrospective studies (OR = 2.19, 95% CI: 1.74-2.74, P < 0.001). Additionally,
      with a multivariate logistic regression analysis adjusted for HPV and age, C.
      trachomatis infection was identified as an independent predictor of cervical
      cancer in 11 studies (OR = 1.76, 95% CI: 1.03-3.01, P = 0.04). Coinfection of
      human papilloma virus and C. trachomatis has a higher risk of cervical cancer (OR
      = 4.03, 95% CI: 3.15-5.16, P < 0.001). A subgroup analysis based on histological
      type indicated an elevated risk for both squamous cell carcinoma (OR = 2.21, 95%
      CI: 2.00-2.45, P < 0.001), and adenocarcinoma (OR = 1.61, 95% CI: 1.21-2.15, P =
      0.001), in associated with C. trachomatis. Subgroup analysis by where C.
      trachomatis infection was detected showed a significantly higher risk of cervical
      cancer associated with C. trachomatis infection detected in serum (OR = 2.20, 95%
      CI: 2.01-2.42, P < 0.001), cervical tissue blocks (OR = 2.88, 95% CI: 1.21-6.83,
      P = 0.02), and cervical secretion (OR = 2.71, 95% CI: 1.41-5.20, P = 0.003),
      especially in serum with no obvious heterogeneity.In conclusion, our novel data
      demonstrate that individuals infected with C. trachomatis have a higher risk of
      cervical cancer. Therefore, it is necessary to expand C. trachomatis infection
      screening and treat women with C. trachomatis promptly, particularly those with
      human papilloma virus infections. This approach will not only protect against
      pelvic inflammatory disease and infertility, but may also prevent cervical
      cancer.

PMID- 27043671
TI  - Olmesartan Combined With Amlodipine on Oxidative Stress Parameters in Type 2
      Diabetics, Compared With Single Therapies: A Randomized, Controlled, Clinical
      Trial.
AB  - To evaluate the effects of a fixed combination of olmesartan/amlodipine compared
      with olmesartan or amlodipine alone on some parameters of endothelial damage in
      diabetic, hypertensive patients.We enrolled 221 patients; 74 were randomized to
      olmesartan 20 mg, 72 to amlodipine 10 mg, and 75 to olmesartan/amlodipine fixed
      combination 20/5 mg for 12 months. We assessed blood pressure monthly; in
      addition, we also assessed at baseline, and after 6 and 12 months, the following
      parameters: lipoprotein (a), myeloperoxidase (MPO), isoprostanes, and paraoxonase
      1 (PON-1). Blood pressure values obtained with fixed olmesartan/amlodipine
      combination were significantly lower than those reached with single
      monotherapies. There was a reduction of lipoprotein (a), and isoprostanes levels
      with olmesartan/amlodipine fixed combination, both compared with baseline, and
      with single monotherapies. On the other hand, there was an increase of PON-1 with
      fixed olmesartan/amlodipine combination, both compared with baseline, and with
      single drugs. All treatments reduced MPO compared with baseline; however, in
      group-to-group comparison, MPO reduction was greater with olmesartan/amlodipine
      fixed combination. Fixed combination of olmesartan/amlodipine was more effective
      than single monotherapies in reducing oxidative stress, especially in increasing
      PON-1, and reducing isoprostanes levels in diabetic and hypertensive patients.

PMID- 27043672
TI  - Certain Autoimmune Manifestations Are Associated With Distinctive Karyotypes and
      Outcomes in Patients With Myelodysplastic Syndrome: A Retrospective Cohort Study.
AB  - Autoimmune manifestations (AIMs) are common in patients with myelodysplastic
      syndrome (MDS). This study aimed to investigate whether AIMs are associated with
      a specific cytogenetic abnormalities and worse survival in patients with MDS. A
      total of 67 MDS patients with AIMs and 134 age- and sex-matched MDS patients
      without AIMs, all of whom received medical care at Seoul National University
      Hospital from January 2000 through July 2014, were enrolled. The clinical
      features, chromosomal abnormalities, and outcomes were examined. The effect of
      AIMs on mortality was estimated after adjusting for age, sex, and the
      International Prognostic Scoring System. The mean age (+/-SD) at the time of MDS
      diagnosis was 54.5 +/- 17.1 years, and 44.8% of patients were male. Neutrophilic
      dermatosis (ND; Sweet syndrome and pyoderma gangrenosum) was the most prevalent
      AIM (n = 24 36%]), followed by Behcet disease (10 [15%]), rheumatoid arthritis (9
      [13%]), vasculitis (8 [12%]), myositis (3 [4%]), spondyloarthropathy (3 [4%]),
      and systemic lupus erythematous (2 [3%]). ND and vasculitis occurred at the time
      of MDS diagnosis, whereas other AIMs occurred years after MDS diagnosis. Deletion
      of 5q was associated with ND (P = 0.001), whereas trisomy 8 was associated with
      Behcet disease (P = 0.015). Strikingly, ND was associated with a 1.8-fold
      increase in mortality (95% CI 1.033-3.093; P = 0.038). Certain AIMs in MDS
      patients are associated with distinctive karyotypes and worse survival. A larger
      study is needed to confirm whether the presence of AIMs influences disease
      outcome in MDS.

PMID- 27043673
TI  - Infundibuloneurohypophysitis Associated With Sjogren Syndrome Successfully
      Treated With Mycophenolate Mofetil: A Case Report.
AB  - Hypophysitis is an inflammatory disorder of the pituitary gland and
      corticosteroids are usually recommended as the first-line treatment. Hypophysitis
      related to primary Sjogren syndrome (pSS) is uncommon. We describe the unusual
      case of a patient with infundibuloneurohypophysitis associated with pSS
      successfully treated with mycophenolate mofetil (MMF).We describe a case of a 60
      year-old man with a medical history of pSS presented with central diabetes
      insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) revealed a
      thickening of the pituitary stalk and intense enhancement of the posterior
      pituitary, pituitary stalk, and hypothalamus. We diagnosed
      infundibuloneurohypophysitis associated with pSS. Hormonal replacement was
      started immediately and MMF was introduced without corticosteroids. After 9
      months of treatment, MRI of the pituitary revealed a complete regression of the
      nodular thickening of the pituitary stalk, with normal enhancement and appearance
      of the pituitary. The pituitary axes had completely recovered, whereas the
      diabetes insipidus was partially restored. Our findings suggest that MMF is an
      effective alternative to corticosteroids for the treatment of lymphocytic
      hypophysitis associated with an autoimmune disease. Furthermore, this report
      could contribute to extend the spectrum of the neurological and endocrinological
      manifestations of pSS.

PMID- 27043674
TI  - Transiliac Osteotomy in Surgical Management of Pelvic Post-Traumatic Malunions: A
      Retrospective Study.
AB  - While uncommon, post-traumatic pelvic malunions present reconstructive challenges
      and are associated with significant disability and financial burden. A transiliac
      osteotomy is a surgical technique useful to correct certain types of pelvic
      fracture malunions, and is only used when the correction of a limb-length
      discrepancy is the primary goal. This study aims to present our experience with
      this technique in the treatment of post-traumatic pelvic malunions. Eight
      patients who underwent transiliac osteotomies for post-traumatic pelvic malunions
      at our department from 2006 to 2011 were included in this study. We reviewed the
      clinical and radiographic results of these patients. By the time of their last
      follow-up, all osteotomy sites and iliac bone graft had healed with no evidence
      of internal fixation failure. Of the 3 patients who complained of preoperative
      posterior pain, 2 reported an improvement. All 8 patients noted the resolution of
      their lower back pain. At the time of their final follow-up, 4 patients could
      walk normally, 2 had a slight limp without a cane, 1 patient used a cane to help
      with standing and walking, and the final felt limited during ambulation with a
      cane. Limb-lengthening relative to preoperative measurements was 2.86 cm (2.2-3.0
      cm) at the time of the last follow-up. Two patients were able to return to their
      previous jobs, 4 patients changed their jobs or engaged in light manual labor
      while the final 2 were able to perform activities of daily living but were unable
      to participate in work or labor. Three patients reported being "extremely
      satisfied" with their outcomes, 3 were "satisfied," and 2 were "unsatisfied." A
      transiliac osteotomy can be used to manage selected cases of post-traumatic
      pelvic malunions that are unable to be corrected with a traditional release and
      osteotomy. However, in these cases the correction of limb-length discrepancies
      should be the primary reconstructive goal.

PMID- 27043675
TI  - Comparison of O-Type HybridKnife to Conventional Knife in Endoscopic Submucosal
      Dissection for Gastric Mucosal Lesions.
AB  - Endoscopic submucosal dissection (ESD) has been accepted as a minimal invasive
      alternative to surgery for localized superficial gastrointestinal neoplasms
      recently. However, the procedure remains to be technically challenging and time
      consuming. A new dissecting knife with partially insulated tip has been recently
      developed with built-in injection capability. The purpose of this study was to
      investigate whether the efficiency of ESD procedure could be improved with this
      new device. A total of 78 patients, who underwent ESD with gastric mucosal
      lesions including flat type polyps, adenoma or early gastric cancer, were
      randomly assigned to either ESD with O-type HybridKnife or conventional ESD
      knives without waterjet. Procedure time and related factors of ESD were analyzed.
      ESD procedure time was 43.0 (interquartile range, IQR 27.0-60.0) minutes in
      HybridKnife group compared to 60.5 (IQR 44.0-86.3) minutes in the control group
      (P = 0.001). There was no difference in the clinical outcome and the adverse
      event rate. The former demonstrated more favorable results in lesions <=4 cm of
      specimen size (P <= 0.0001) and when located in the distal stomach (P = 0.001),
      also in lesions with fibrosis (P = 0.008). Multivariate regression analysis
      showed that O-type Knife (P <= 0.0001), specimen size (P <= 0.0001), and fibrosis
      (P <= 0.0001) were independent predictors of procedure time. The O-type
      HybridKnife yielded faster procedure time compared to the conventional knives in
      gastric ESD with a similar safety profile.

PMID- 27043676
TI  - Prognostic Significance of 2-Deoxy-2-[18F]-Fluoro-D-Glucose PET/CT in Patients
      With Locally Advanced Esophageal Cancer Undergoing Neoadjuvant Chemoradiotherapy
      Before Surgery: A Nonparametric Approach.
AB  - To investigate the prognostic value of tumor metabolism measurements on serial 2
      deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed
      tomography scans in patients with locally advanced esophageal cancer undergoing
      neoadjuvant chemoradiotherapy. Forty-five patients (63 +/- 7 years, 6 female)
      treated with concomitant chemoradiotherapy before surgery were followed up for 24
      +/- 18 months (range 4-71). Positron emission tomography and computed tomography
      scans were obtained within 1 week before the start (PET1) and 1 month after the
      completion of the treatment (PET2). Total body tumor metabolic activity was
      measured as the sum of the parameters: SUVmax, SUV corrected for lean body mass,
      and total lesion glycolysis (TLG40/50/70%). Then, delta values for the parameters
      between PET1 and PET2 were calculated and expressed as percentage of PET1
      results. At the time of the analysis, 27 patients were dead and 18 were alive.
      There was no difference between the 2 groups in terms of age, sex, site of the
      disease, histology, and the presence/absence of linfonodal metastases (P = NS).
      Survival random forest analysis (20,000 trees) resulted in an estimate of error
      rate of 36%. The nonparametric approach identified DeltaTLG40 as the most
      predictive factor of survival (relative importance 100%). Moreover, T (17%), N
      (5%), and M (5%) stage of the disease, cancer histology (11%), TLG70 (5%) at the
      end of chemioradioterapy, and DeltaTLG(50-70) (17%-5%) were positively associated
      with patient outcome. The nonparametric analysis confirmed the prognostic
      importance of some clinical parameters, such as TNM stage and cancer histology.
      Moreover, DeltaTLG resulted to be the most important factor in predicting outcome
      and should be considered in risk stratification of patients treated with
      neoadjuvant chemoradiotherapy.

PMID- 27043677
TI  - Sarcopenia is an Independent Predictor of Severe Postoperative Complications and
      Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a
      Large-Scale Cohort.
AB  - Currently, the association between sarcopenia and long-term prognosis after
      gastric cancer surgery has not been investigated. Moreover, the association
      between sarcopenia and postoperative complications remains controversial. This
      large-scale retrospective study aims to ascertain the prevalence of sarcopenia
      and assess its impact on postoperative complications and long-term survival in
      patients undergoing radical gastrectomy for gastric cancer. From December 2008 to
      April 2013, the clinical data of all patients who underwent elective radical
      gastrectomy for gastric cancer were collected prospectively. Only patients with
      available preoperative abdominal CT scan within 30 days of surgery were
      considered for analysis. Skeletal muscle mass was determined by abdominal
      (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values
      obtained by means of optimum stratification. Univariate and multivariate analyses
      evaluating risk factors of postoperative complications and long-term survival
      were performed. A total of 937 patients were included in this study, and 389
      (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9
      cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk
      factor for severe postoperative complications (OR = 3.010, P < 0.001), but not
      for total complications. However, sarcopenia did not show significant association
      with operative mortality. Moreover, sarcopenia was an independent predictor for
      poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR =
      1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage,
      sarcopenia remained an independent risk factor for overall survival and disease
      free survival in patients with TNM stage II and III, but not in patients with TNM
      stage I. Sarcopenia is an independent predictive factor of severe postoperative
      complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia
      is independently associated with overall and disease-free survival in patients
      with TNM stage II and III, but not in patients with TNM stage I.

PMID- 27043678
TI  - Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but
      Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following
      the PRISMA Guidelines.
AB  - Bupropion is widely used for treating bipolar disorder (BD), and especially those
      with depressive mood, based on its good treatment effect, safety profile, and
      lower risk of phase shifting. However, increasing evidence indicates that the
      safety of bupropion in BD patients may not be as good as previously thought. The
      aim of this study was to summarize data on the treatment effect and safety
      profile of bupropion in the treatment of BD via a meta-analysis. Electronic
      search through PubMed and ClinicalTrials.gov was performed. The inclusion
      criteria were: (i) studies comparing changes in disease severity before and after
      bupropion treatment or articles comparing the treatment effect of bupropion in BD
      patients with those receiving other standard treatments; (ii) articles on
      clinical trials in humans. The exclusion criteria were (i) case reports/series,
      and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled
      using a random effects model. We examined the possible confounding variables
      using meta-regression and subgroup analysis. Bupropion significantly improved the
      severity of disease in BD patients (P < 0.001), and the treatment effect was
      similar to other antidepressants/standard treatments (P = 0.220). There were no
      significant differences in the dropout rate (P = 0.285) and rate of phase
      shifting (P = 0.952) between BD patients who received bupropion and those who
      received other antidepressants. We could not perform a detailed meta-analysis of
      every category of antidepressant, nor could we rule out the possible confounding
      effect of concurrent psychotropics or include all drug side effects. Furthermore,
      the number of studies recruited in the meta-analysis was relatively small. Our
      findings reconfirm the benefits of bupropion for the treatment of bipolar
      depression, which are similar to those of other antidepressants. However, the
      rate of phase shifting with bupropion usage was not as low compared to other
      antidepressants as previously thought, which should serve to remind clinicians of
      the risk of phase shifting when prescribing bupropion to BD patients regardless
      of the suggestions of current clinical practice guidelines.

PMID- 27043679
TI  - Understanding Cross-Sectional Racial, Ethnic, and Gender Disparities in
      Antiretroviral Use and Viral Suppression Among HIV Patients in the United States.
AB  - To examine racial/ethnic and gender disparities in antiretroviral (ART) use and
      viral suppression among HIV-infected persons in care and identify factors that
      might account for observed disparities. The Medical Monitoring Project (MMP) is a
      complex sample survey of HIV-infected adults receiving medical care in the United
      States. We used weighted interview and medical record data collected 06/2009 to
      05/2012 to estimate the prevalence of ART use and viral suppression among gender
      stratified racial/ethnic groups. We used chi2 tests to identify significant
      differences in outcomes between white men versus other groups, and logistic
      regression models to identify the most parsimonious set of factors that could
      account for each observed difference. We found no significant disparity in ART
      use between white and Hispanic men, and no disparities between white men and
      white and Hispanic women after adjustment for disease stage, age, and poverty.
      Disparities in ART use between white men and black persons persisted after
      adjusting for other factors, but the observed differences were relatively small.
      Differences in ART use and adherence, demographic characteristics, and social
      determinants of health such as poverty, education, and insurance accounted for
      the observed disparities in viral suppression between white men and all groups
      except black men. In our model, accounting for these factors reduced the
      prevalence difference in viral suppression between white and black men by almost
      half. We found that factors associated with disparities differed among men and
      women of the same race/ethnicity, lending support to the assertion that gender
      affects access to care and health status among HIV-infected patients. In addition
      to supporting efforts to increase ART use and adherence among persons living with
      HIV, our analysis provides evidence for the importance of social determinants of
      health in understanding racial/ethnic and gender differences in ART use and viral
      suppression.

PMID- 27043680
TI  - Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10
      Years After Treatment With Mitotane Monotherapy: Case Report and Review of the
      Literature.
AB  - Mitotane has been used for more than 5 decades as therapy for adrenocortical
      carcinoma (ACC). However its mechanism of action and the extent of tumor response
      remain incompletely understood. To date no cases of rapid and complete remission
      of metastatic ACC with mitotane monotherapy has been reported. A 52-year-old
      French Canadian man presented with metastatic disease 2 years following a right
      adrenalectomy for stage III nonsecreting ACC. He was started on mitotane which
      was well tolerated despite rapid escalation of the dose. The patient course was
      exceptional as he responded to mitotane monotherapy after only few months of
      treatment. Initiation of chemotherapy was not needed and he remained disease-free
      with good quality of life on low maintenance dose of mitotane during the
      following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p.
      Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic beta
      catenin were positive. Advanced ACC is an aggressive disease with poor prognosis
      and the current therapeutic options remain limited. These findings suggest that
      mitotane is a good option for the treatment of metastatic ACC and might result in
      rapid complete remission in selected patients.

PMID- 27043681
TI  - Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory
      Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large
      Artery Atherosclerotic Stroke: A Randomized Trial.
AB  - Statins have beneficial effects on cerebral circulation and brain parenchyma
      during ischemic stroke and reperfusion. The primary hypothesis of this randomized
      parallel trial was that treatment with 80 mg/day of atorvastatin administered
      early at admission after acute atherosclerotic ischemic stroke could reduce serum
      levels of markers of immune-inflammatory activation of the acute phase and that
      this immune-inflammatory modulation could have a possible effect on prognosis of
      ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients
      with acute ischemic stroke classified as large arteries atherosclerosis stroke
      (LAAS) randomly assigned in a randomized parallel trial to the following groups:
      Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission
      day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg
      until discharge, and after discharge, treatment with atorvastatin has been
      started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group
      A showed significantly lower plasma levels of tumor necrosis factor-alpha,
      interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant
      difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was
      observed between the 2 groups. At 72 hours and 7 days after admission, stroke
      patients treated with atorvastatin 80 mg in comparison with stroke subjects not
      treated with atorvastatin showed a significantly lower mean National Institutes
      of Health Stroke Scale and modified Rankin scores. Our findings provide the first
      evidence that atorvastatin acutely administered immediately after an
      atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory
      activation of the acute phase of stroke and that its early use is associated to a
      better functional and prognostic profile.

PMID- 27043682
TI  - First Case Report of Acute Renal Failure After Mesh-Plug Inguinal Hernia Repair
      in a Kidney Transplant Recipient.
AB  - Acute renal failure due to ureter compression after a mesh-plug inguinal repair
      in a kidney transplant recipient has not been previously reported to our
      knowledge. A 62-year-old man, who successfully underwent kidney transplantation
      from a deceased donor 6 years earlier, was admitted for elective repair of a
      direct inguinal hernia. The patient underwent an open mesh-plug repair of the
      inguinal hernia with placement of a plug in the preperitoneal space. We did not
      observe the transplanted ureter and bladder during dissection of the inguinal
      canal. Immediately after surgery, the patient became anuric, and a graft
      sonography demonstrated massive hydronephrosis. The serum creatinine level
      increased rapidly, and the patient underwent an emergency reoperation 8 hours
      later. During surgery, we did not identify the ureter but, immediately after plug
      removal, urine output increased progressively. We completed the hernia repair
      using the standard technique, without plug interposition, and the postoperative
      course was uneventful with complete resolution of graft dysfunction 3 days later.
      Furthermore, we reviewed the clinical features of complications related to
      inguinal hernia surgery. An increased risk of urological complications was
      reported recently in patients with a previous prosthetic hernia repair undergoing
      kidney transplantation, mainly due to the mesh adhesion to surrounding
      structures, making the extraperitoneal dissection during the transplant surgery
      very challenging. Moreover, older male kidney transplant recipients undergoing an
      inguinal hernia repair may be at higher risk of graft dysfunction due to inguinal
      herniation of a transplanted ureter. Mesh-plug inguinal hernia repair is a safe
      surgical technique, but this unique case suggests that kidney transplant
      recipients with inguinal hernia may be at higher risk of serious urological
      complications. Surgeons must be aware of the graft and ureter position before
      proceeding with hernia repair. A prompt diagnosis with graft sonography and
      abdominal computed tomography scan and emergency surgery may avoid the need for
      nephrostomy and may resolve graft dysfunction more rapidly.

PMID- 27043683
TI  - Prognostic Factors of the Efficacy of High-dose Corticosteroid Therapy in
      Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome During
      Pregnancy: A Meta-analysis.
AB  - The aim of this study was to identify the factors which can affect the efficacy
      of corticosteroid (CORT) therapy in the management of hemolysis, elevated liver
      enzymes, and low platelet count (HELLP) syndrome. Research articles reporting the
      efficacy of CORT therapy to HELLP syndrome patients were searched in several
      electronic databases including EMBASE, Google Scholar, Ovid SP, PubMed, and Web
      of Science. Study selection was based on predefined eligibility criteria.
      Efficacy was defined by the changes from baseline in HELLP syndrome indicators
      after CORT therapy. Meta-analyses were carried out with Stata software. Data of
      778 CORT-treated HELLP syndrome patients recruited in 22 studies were used in the
      analyses. Corticosteroid treatment to HELLP syndrome patients was associated with
      significant changes from baseline in platelet count; serum levels of aspartate
      aminotransaminase, alanine transaminase, and lactic dehydrogenase (LDH); mean
      blood pressure; and urinary output. Lower baseline platelet count predicted
      higher change in platelet count after CORT therapy. Lower baseline platelet count
      and lower baseline urinary output predicted greater changes in LDH levels after
      CORT therapy. There was also an inverse relationship between the change from
      baseline in LDH levels and intensive care duration. Higher CORT doses were
      associated with greater declines in the aspartate aminotransaminase, alanine
      transaminase, and LDH levels. Incidence of cesarean delivery was inversely
      associated with the gestation age. The percentage of nulliparous women had a
      positive association with the intensive care stay duration. High-dose CORT
      therapy to HELLP syndrome patients provides benefits in improving disease markers
      and reducing intensive care duration, especially in cases such as mothers with
      much lower baseline platelet count and LDH levels.

PMID- 27043684
TI  - ECMO Used in a Refractory Ventricular Tachycardia and Ventricular Fibrillation
      Patient: A National Case-Control Study.
AB  - Refractory cardiac arrhythmia, which has a poor response to defibrillation and
      antiarrhythmia medication, is a complicated problem for clinical physicians
      during resuscitation. Extracorporeal membrane oxygenation (ECMO) may be used to
      sustain life in this situation. ECMO is useful for cardiopulmonary resuscitation
      among patients suffering from cardiac arrest; the use of ECMO in this context is
      called E-cardiopulmonary resuscitation. However, a large-scale and nationwide
      survey of ECMO usage in cases involving refractory cardiac arrhythmia during
      resuscitation is lacking. We aimed to clarify the characteristics and efficacy of
      the application of ECMO in cases involving refractory cardiac arrhythmia during
      resuscitation by conducting a nationwide study. Using national insurance data
      from 1996 to 2011, 2702 patients who received defibrillation and amiodarone
      injections were selected. We excluded trauma patients (n = 316) and those aged<20
      years (n = 24). A total of 2362 patients were included, 376 of whom had ECMO
      support, and 1986 of whom had no ECMO support. After propensity score matching,
      320 patients had ECMO support and 640 patients without ECMO support. Conditional
      logistic regression was used to estimate the risk of death in ECMO users compared
      to non-EMCO users. ECMO used in refractory cardiac arrhythmia with high
      propensity score patients had lower risk of death (odds ratio [OR] = 0.59, 95%
      confidence interval [CI] = 0.36-0.98). However, prolonged ECMO used >1 day was
      higher risk of death (OR = 2.88, 95% CI = 1.27-6.53). In our retrospective case
      control study in refractory cardiac arrhythmia patients, ECMO supportive in high
      propensity score patients showed improving the overall survival rate but ECMO
      support for >1 day would be harmful. The evidence derived from this retrospective
      study using data from the national insurance system is generally of lower
      methodological evidence than that from randomized controlled trials because a
      retrospective study is subject to many biases due to lack of the necessary
      adjustments for possible confounding factors. Therefore, further investigation
      with a randomized clinical trial is needed to recommend ECMO as a routine in this
      specific population of patients experiencing cardiac arrest and refractory VT and
      VF.

PMID- 27043685
TI  - Gray Matter Involvement in Radiologically Isolated Syndrome.
AB  - The unanticipated magnetic resonance imaging (MRI) detection in the brain of
      asymptomatic subjects of white matter lesions suggestive of multiple sclerosis
      has recently been named as radiologically isolated syndrome (RIS). The
      pathophysiological processes of RIS remain largely unknown and questions as to
      whether gray matter alterations actually occur in this entity are yet to be
      investigated in more detail. By means of a 3 T multimodal MRI approach, we
      searched for cortical and deep gray matter changes in a cohort of RIS patients.
      Seventeen RIS patients, 17 clinically isolated syndrome (CIS) patients (median
      disease duration from symptom onset = 12 months), and 17 healthy controls
      underwent MRI and neuropsychological testing. Normalized deep gray matter volumes
      and regional cortical thickness were assessed using FreeSurfer. SIENAX was used
      to obtain normalized global and cortical brain volumes. Voxelwise morphometry
      analysis was performed by using SPM8 software to localize regions of brain tissue
      showing significant changes of fractional anisotropy or mean diffusivity.
      Although no differences were observed between CIS and healthy controls groups,
      RIS patients showed significantly lower normalized cortical volume (673 +/- 27.07
      vs 641 +/- 35.88 [cm3 * 103, Tukey P test = 0.009) and mean thalamic volume
      (0.0051 +/- 0.4 vs 0.0046 +/- 0.4 mm, P = 0.014) compared with healthy controls.
      RIS patients also showed significant thinning in a number of cortical areas, that
      were primarily distributed in frontal and temporal lobes (P < 0.05, uncorrected).
      Strong correlations were observed between T2-white matter lesion volume and
      regional cortical thickness (rho spearman ranging from 0.60 to 0.80). Our data
      suggest that white matter lesions on T2-weighted images are not the only hallmark
      of RIS. Future longitudinal studies with larger samples are warranted to better
      clarify the effect of RIS-related white matter lesions on gray matter tissue.

PMID- 27043686
TI  - A Retrospective Study of Chinese Patients With Giant Cell Arteritis (GCA):
      Clinical Features and Factors Associated With Severe Ischemic Manifestations.
AB  - A retrospective study was performed on 70 giant cell arteritis (GCA) patients in
      Peking Union Medical College Hospital (PUMCH). The aim of this study was to
      describe the clinical features of these Chinese GCA patients and explore the
      possible associated factors for severe ischemic manifestations. Medical charts of
      all patients were reviewed, and the demographic, clinical, and laboratory data
      were analyzed. The mean age at disease onset was 65.2 years old, and the ratio of
      male to female was 1:1. Fever and headache were most prominent symptoms at onset,
      which occurred in 51.4% and 30.0% of patients, respectively. Common
      manifestations at diagnosis were constitutional symptoms (85.7%), headache
      (68.8%), visual impairment (38.6%), jaw claudication (30%), scalp tenderness
      (30%), and concurrent polymyalgia rheumatic (27.1%). No significant difference in
      clinical manifestations between genders was observed. Comparisons between
      patients with and without severe ischemic manifestations including jaw
      claudication, permanent visual loss, or cerebrovascular accident had shown that
      fever and asthenia were significantly less frequent in patients with severe
      ischemic manifestations (P = 0.006 and 0.023, respectively), and the mean value
      of erythrocyte sedimentation rate (ESR) was significantly lower in patients with
      severe ischemic manifestations than patients without (P = 0.001). History of
      smoking was more frequent in patients with severe ischemic manifestations (P =
      0.038). This is the largest group of GCA patients from China so far. When
      compared our data with patients reported in the literature, this series of GCA
      patients were younger and without female predominance. The clinical
      manifestations of patients in this report were similar to other studies except
      for a higher prevalence of constitutional symptoms. The results of this study
      indicated that lower systemic inflammatory response and the history of smoking
      might be associated with severe ischemic damages.

PMID- 27043687
TI  - Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After
      Cardiac Surgery.
AB  - Acute kidney injury (AKI) after cardiac surgery is a common and serious
      complication. Although lower than normal serum bicarbonate levels are known to be
      associated with consecutive renal function deterioration in patients with chronic
      kidney injury, it is not well-known whether preoperative low serum bicarbonate
      levels are associated with the development of AKI in patients who undergo cardiac
      surgery. Therefore, the clinical implication of preoperative serum bicarbonate
      levels on AKI occurrence after cardiac surgery was investigated. Patients who
      underwent coronary artery bypass or valve surgery at Yonsei University Health
      System from January 2013 to December 2014 were enrolled. The patients were
      divided into 3 groups based on preoperative serum bicarbonate levels, which
      represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23
      to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the
      predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined
      according to Acute Kidney Injury Network criteria. Among 875 patients, 228
      (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI
      was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P <
      0.001). In addition, the duration of postoperative stay in a hospital intensive
      care unit (ICU) was longer for AKI patients and for those in the low-preoperative
      serum-bicarbonate-level groups. A multivariate logistic regression analysis
      showed that low preoperative serum bicarbonate levels were significantly
      associated with AKI even after adjustment for age, sex, hypertension, diabetes
      mellitus, operation type, preoperative hemoglobin, and estimated glomerular
      filtration rate. In conclusion, low serum bicarbonate levels were associated with
      higher incidence of AKI and prolonged ICU stay. Further studies are needed to
      clarify whether strict correction of bicarbonate levels close to normal limits
      may have a protective role in preventing further AKI development. 

PMID- 27043688
TI  - Significantly Higher Prevalence Rate of Asthma and Bipolar Disorder Co-Morbidity:
      A Meta-Analysis and Review Under PRISMA Guidelines.
AB  - Asthma and bipolar disorder (BD) are 2 distinct diseases that share similar
      pathophysiology. This study aimed to determine their relationship thorough a meta
      analysis of articles on their comorbidity rate. The aim of the study is to
      examine the overall prevalence rate of BD in asthmatic patients and of asthma in
      BD patients compared to healthy controls. Electronic research of PubMed and
      ClinicalTrials.gov was performed. Articles discussing the prevalence rate of BD
      in patients with/without asthma and the prevalence rate of asthma in those
      with/without BD, as well as clinical trials in humans and case-controlled trials
      or cohort studies, were all included. Case reports or series and nonclinical
      trials were excluded. Through a random-effects model, a meta-analysis of the
      results of 4 studies comparing the prevalence rate of BD in patients with/without
      asthma, and in 6 studies comparing the prevalence rate of asthma in subjects
      with/without BD were performed. There were significantly higher prevalence rates
      of BD in asthmatic patients than in healthy controls (P < 0.001) and of asthma in
      BD patients than in healthy controls (P < 0.001). Only the patient's mean age
      significantly modulated the odds ratio of the prevalence rate of asthma in BD
      patients (slope = 0.015, P < 0.001). Only 10 studies were included and most were
      cross-sectional studies. The possible confounding effect of medication on BD or
      asthma onset was not investigated. Any possible etiology of the comorbidity was
      also not determined. This meta-analysis highlights the importance of the
      significantly high comorbid rate of BD and asthma, and the positive association
      with age. Special attention must be given to the comorbidity of asthma and BD,
      especially in older patients.

PMID- 27043689
TI  - Prognostic Significance of Central Pulse Pressure for Mortality in Patients With
      Coronary Artery Disease Receiving Repeated Percutaneous Coronary Intervention.
AB  - Coronary artery disease (CAD) is a life-threatening medical emergency which needs
      urgent medical attention. Percutaneous coronary intervention (PCI) is common and
      necessary for patients with CAD, but it has not completely evaluated in cases
      with repeated PCI. Therefore, the aim of this study was to examine the risk
      factors and prognosis in patients with CAD requiring repeated PCI. This is a
      prospective observational study. A total of 1126 patients with CAD requiring PCI
      took part in this study. Clinical parameters including baseline characteristics,
      hemodynamic data, location of vascular lesions, SYNTAX score, left ventricular
      ejection fraction, central pulse pressure (CPP), central aortic systolic pressure
      (CSP), risk factors, and invasive strategies were analyzed to identify the risk
      factors for patients requiring repeated PCI. We further analyzed the prognosis,
      including risk for myocardial infarction (MI), cardiovascular (CV) mortality, and
      all-cause mortality, in patients with repeated PCI. Among patients with PCI, 276
      received repeated PCI. Patients in the repeated PCI group had a higher CPP (66.7
      vs 62.5 mm Hg; P = 0.006), CSP (139.9 vs 135.9 mm Hg; P = 0.017), and male
      preponderance (P = 0.012). Drugs including diuretics, beta-blockers (BBs),
      angiotensin-converting enzyme inhibitors (ACEIs), and aspirin were all used more
      frequently in the repeated PCI group (all P < 0.05). Freedom from MI was lower in
      the repeated PCI group than in the single PCI group (P < 0.001). Logistic
      regression revealed that CPP, CSP, number of diseased vessels, male sex, usage of
      diuretics, BBs, ACEIs, and MI were all predictors for requiring repeated PCI (all
      P < 0.05). In addition, CPP was a predictor for MI attack, CV mortality, and all
      cause mortality in the repeated PCI group (P = 0.010, P = 0.041, P = 0.004,
      respectively). Elevated CPP, CSP, male sex, multiple diseased vessels, and the
      usage of diuretics, BBs, ACEIs, and MI were predictors for repeated PCI. Most
      importantly, CPP was strongly associated with MI attack, CV mortality, and all
      cause mortality, and could serve as a prognostic parameter for mortality in
      patients with CAD after performing repeated PCI.

PMID- 27043690
TI  - Mast Cells Comprise the Major of Interleukin 17-Producing Cells and Predict a
      Poor Prognosis in Hepatocellular Carcinoma.
AB  - IL-17 and IL-17-producing cells have been found in many types of human cancers
      and murine models. However, the source of tumor-infiltrating IL-17 and IL-17
      producing cells in HCC and the prognostic values remain poorly understood. A
      total of 57 HCC patients were enrolled in this study, and immunofluorescence
      double stain was used to evaluate the colocalization of CD3 T cells, CD4 T cells,
      CD56 NK cells, CD20 B cells, CD68 Macrophages, and MCT mast cells with IL-17. The
      prognostic value of IL-17-producing cells was evaluated by Kaplan-Meier analysis
      and Cox regression model. MCT mast cells, but not other cells, were the
      predominant IL-17-producing cell type. Overall survival analysis revealed that
      the increasing intratumoral-infiltrated MCT mast cells were significantly
      associated with poor prognosis. Immunofluorescence double stain showed a positive
      correlation between the number of MCT mast cells and MCVs. These findings
      indicated the major IL-17-producing cells in HCC were MCT mast cells and these
      cells infiltration may promote tumor progression by angiogenesis. Increased MCT
      mast cells was associated with a poor prognosis, indicating therapy targeting MCT
      mast cells might be an effective strategy in controlling intratumor IL-17
      infiltration and MCVs.

PMID- 27043691
TI  - Low Serum Fetuin-A as a Biomarker to Predict Pneumococcal Necrotizing Pneumonia
      and Hemolytic Uremic Syndrome in Children.
AB  - Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive
      pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in
      humans. We aimed to identify serum sialoglycoproteins that are targeted by
      neuraminidases in severe pneumococcal infection. We hypothesized that serum
      sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or
      HUS. We constructed serum sialoglycoprotein profiles before and after
      pneumococcal neuraminidase treatment using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS), a proteomic approach. An observational study was
      conducted using clinical data and serum samples from pediatric patients with
      pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum
      fetuin-A levels were determined by enzyme-linked immunosorbent assay. The most
      abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase
      treatment and peanut lectin capture were immunoglobulins, apolipoproteins,
      fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A
      levels in the HUS patients were significantly lower (207 +/- 80 mg/L, P < 0.001)
      than in patients with lobar pneumonia (610 +/- 190 mg/L) as well as the healthy
      controls (630 +/- 250 mg/L). In comparing HUS with necrotizing pneumonia and
      lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298
      mg/L yielded sensitivity of 92.9% (95% CI: 68.5-98.7%) and specificity of 71.9%
      (95% CI: 54.6-84.4%). This observational study with validation cohorts of
      patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the
      high performance of low serum fetuin-A levels as a biomarker to predict severe
      IPD and HUS in children.

PMID- 27043692
TI  - Clinical Value of Assessing Cytokine Levels for the Differential Diagnosis of
      Bacterial Meningitis in a Pediatric Population.
AB  - We performed a prospective observational study to evaluate the utility of
      measuring inflammatory cytokine levels to discriminate bacterial meningitis from
      similar common pediatric diseases. Inflammatory cytokine levels and other
      cerebrospinal fluid (CSF) physicochemical indicators were evaluated in 140
      patients who were diagnosed with bacterial meningitis via microbiological culture
      or PCR assay. The CSF concentrations of interleukin (IL)-6 and IL-10, CSF/blood
      IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein
      were significantly elevated in bacterial meningitis patients compared with
      healthy children or patients with viral encephalitis, epilepsy, or febrile
      convulsions (P < 0.001). The area under the curve values for CSF concentrations
      of IL-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count,
      and CSF micro total protein to identify bacterial meningitis episodes by receiver
      operating characteristic analysis were 0.988, 0.949, 0.995, 0.924, 0.945, and
      0.928, respectively. The area under the curve for the combination of CSF IL-6 and
      CSF/blood IL-6 ratio was larger than that for either parameter alone, and the
      combination exhibited enhanced specificity and positive predictive value. After
      effective meningitis treatment, CSF IL-6 levels dropped significantly. These
      results suggest that CSF IL-6 and CSF/blood IL-6 ratio are good biomarkers in
      discriminating bacterial meningitis. Evaluating CSF IL-6 and CSF/blood IL-6 ratio
      in combination can improve diagnostic efficiency. Additionally, CSF IL-6 levels
      can be used to monitor the effects of bacterial meningitis treatment.

PMID- 27043693
TI  - A Case Report of Cannabis Induced Hemoptysis.
AB  - As the principal route of marijuana use is by inhalation, potential harmful
      consequences on pulmonary structure and function can be anticipated. Here, we
      present a case of hemoptysis attributed to smoking cannabis in a 38-year-old man.
      The patient experienced an episode of hemoptysis and shortness of breath
      immediately after smoking marijuana. Chest radiograph and computed tomography
      (CT) scans of the chest showed bilateral diffuse ground-glass opacities. A fiber
      optic bronchoscopy confirmed bilateral diffuse bleeding from respiratory tract.
      Additional evaluation of hemoptysis indicated no infection or immunological
      responses. Urine toxicology was positive for cannabis. Chronic marijuana smoking
      causes visible and microscopic injury to the larger airways responsible for
      symptoms or chronic bronchitis. We review the beneficial and deleterious effects
      of marijuana and describe a case of significant hemoptysis attributed to smoking
      marijuana. In addition to other respiratory complications of marijuana use,
      physicians should educate their patients about this potentially lethal effect of
      marijuana smoking in the form of hemoptysis.

PMID- 27043694
TI  - DWI as a Quantitative Biomarker in Predicting Chemotherapeutic Efficacy at
      Multitime Points on Gastric Cancer Lymph Nodes Metastases.
AB  - The purpose of the hypothesis testing is to determine that apparent diffusion
      coefficient (ADC) as an early biomarker can predict the metastatic lymph nodes'
      (LNs) response to neoadjuvant chemotherapy in advanced gastric cancer (GC) in
      early stage. From March 2011 to June 2015, 106 patients with advanced GC were
      enrolled in the study. Patients underwent conventional magnetic resonance imaging
      and functional diffusion weighted imaging before and 3 days, 7 days, 30 days, and
      60 days following the standard chemotherapy. After surgery, among 3034 detected
      LNs, the positive group was divided into complete response (CR) group, partial
      response (PR) group, and stable disease (SD) group in accordance to the Response
      Evaluation Criteria in Solid Tumors (RECIST) 1.1. Mean ADCs, short/long diameters
      of LNs before chemotherapy between the whole positive and the negative LNs were
      compared by t test. Changes of mean ADCs in 3 groups were analyzed by 1-way
      ANOVA. The mean ADC of the whole positive LNs was (1.145 +/- 0.014) * 10-3 mm2/s,
      which was significantly lower than that of the whole negative LNs ([1.491 +/-
      0.010] * 10-3 mm2/s; P < 0.05). The means of both short/long diameters in the
      whole positive LNs were significantly longer than those in the whole negative LNs
      (P < 0.05). In CR, PR, and SD groups, the mean ADC of metastatic LNs on the 3rd
      day, 7th day, 13th day, and 16th day following the chemotherapy were all higher
      than that of LNs before chemotherapy, respectively (all P < 0.05). In addition,
      significant difference was found between mean ADCs in any 2 time points (all P <
      0.05), except between mean ADCs in the 3rd day and in the 7th day of the
      chemotherapy. In conclusion, ADC can be used as an early biomarker to predict the
      metastatic LNs' response to neoadjuvant chemotherapy in advanced GC in early
      stage.

PMID- 27043695
TI  - Incidence and Risk Factors Associated With Hospitalization for Variant Angina in
      Korea.
AB  - This study aimed to determine the incidence and the risk factors of
      hospitalization for variant angina (VA) in Korean patients. Using the National
      Inpatient Sample (NIS) database, manufactured and released by the Health
      Insurance Review and Assessment Service (HIRA) in Korea, the incidence of
      hospitalization and rehospitalization for VA were calculated. The numbers of
      patients hospitalized for VA were estimated to be 14,362 in 2009, 17,492 in 2010,
      and 20,592 in 2011. The standardized incidence rates of hospitalization for VA
      were 31.4% in 2009, 36.5% in 2010, and 41.7% in 2011 (relative increase rate from
      2009 to 2011, 33.0%, P for trend < 0.0001). VA patients predominantly belonged to
      the middle-age group between 40 and 69 years (75.5%), and there were 54.3% male.
      Based on the hospitalization episodes, the number of rehospitalization was
      calculated to be 879, 1141, and 1446 patients out of 1867, 2274, and 2677
      patients from 2009, 2010, and 2011, respectively. The rates of rehospitalization
      for VA were 47.1% in 2009, 50.2% in 2010, and 54.0% in 2011 (P for trend <
      0.0001). Age was an independent factor associated with rehospitalization for VA.
      Hospitalization for VA occurred most frequently in fall from 2009 to 2011. In
      conclusion, hospitalization rates for VA steadily increased from 2009 to 2011 in
      Korea, and about a half of VA patients was hospitalized more than once a year in
      2009 to 2011. Proper health policy and patient education are warranted to control
      the high rate of hospitalization for VA. 

PMID- 27043696
TI  - Comparison of Risk Scoring Systems to Predict the Outcome in ASA-PS V Patients
      Undergoing Surgery: A Retrospective Cohort Study.
AB  - Operative decision in American Society of Anesthesiology Physical Status (ASA-PS)
      V patient is difficult as this group of patients expected to have high mortality
      rate. Another risk scoring system in this ASA-PS V subset of patients can aid to
      ease this decision. Data of ASA-PS V classified patients between 2011 and 2013
      years in a single hospital were analyzed in this study. Predicted mortality of
      these patients was determined with acute physiology and chronic health
      evaluations (APACHE) II, simplified acute physiology score (SAPS II), Charlson
      comorbidity index (CCI), Porthsmouth physiological and operative severity score
      for enumeration of mortality and morbidity (P-POSSUM), Surgical apgar score
      (SAS), and Goldman cardiac risk index (GCRI) scores. Observed and predicted
      mortality rates according to the risk indexes in these patients were compared at
      survivor and nonsurvivor group of patients. Risk stratification was made with
      receiver operator characteristic (ROC) curve analysis. Data of 89 patients were
      included in the analyses. Predicted mortality rates generated by APACHE II and
      SAPS II scoring systems were significantly different between survivor and
      nonsurvivor group of patients. Risk stratification with ROC analysis revealed
      that area under curve was 0.784 and 0.681 for SAPS II and APACHE II scoring
      systems, respectively. Highest sensitivity (77.3) is reached with SAPS II score.
      APACHE II and SAPS II are better predictive tools of mortality in ASA-PS V
      classified subset of patients. Discrimination power of SAPS II score is the best
      among the compared risk stratification scores. SAPS II can be suggested as an
      additional risk scoring system for ASA-PS V patients.

PMID- 27043697
TI  - Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in
      Invasive Breast Cancer.
AB  - Chemotherapy-induced neutropenia (CIN) was the most apparent side effects of bone
      marrow suppression with adjuvant chemotherapy. Recently, several studies revealed
      that CIN may predict better outcomes. However, the researches upon breast cancer
      were still indefinite. We reviewed the female patients with pathologically
      diagnosed invasive breast cancer at the First Affiliated Hospital of Wenzhou
      Medical University, between Jan 2008 and Dec 2010. The lowest neutrophil counts
      in the second week after the first cycle of chemotherapy were collected.
      Clinicopathological characteristics and survival rates were compared and analyzed
      between the CIN group and non-CIN group. The median follow-up time was 62 months.
      The differences of over-all survival and local recurrence-free survival between
      the 2 groups were nonsense (P = 0.938, P = 0.695, respectively). But the disease
      free survival and distant metastasis-free survival of the CIN group were
      statically significantly better (HR = 0.391, P = 0.009, and HR = 0.315, P =
      0.005, respectively). The bone metastasis-free survival may be responsible for
      the differences (HR = 0.469, P = 0.005). Subgroup analyses showed the CIN may
      predict lower bone metastases rates with ER positive status, premenopause or
      younger age (<= 40) (P = 0.002, P = 0.004, and P = 0.0001, respectively). Cox
      analysis showed younger ages, N staging, and the presence of CIN were associated
      with bone metastasis-free survival independently adjusting to peritumoral
      vascular invasion (P < 0.05). CIN may predict a decreased recurrence risk of
      breast cancer, especially bone metastases.

PMID- 27043698
TI  - Learning Curve of the Application of Huang Three-Step Maneuver in a Laparoscopic
      Spleen-Preserving Splenic Hilar Lymphadenectomy for Advanced Gastric Cancer.
AB  - To investigate the learning curve of the application of Huang 3-step maneuver,
      which was summarized and proposed by our center for the treatment of advanced
      upper gastric cancer. From April 2012 to March 2013, 130 consecutive patients who
      underwent a laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL)
      by a single surgeon who performed Huang 3-step maneuver were retrospectively
      analyzed. The learning curve was analyzed based on the moving average (MA) method
      and the cumulative sum method (CUSUM). Surgical outcomes, short-term outcomes,
      and follow-up results before and after learning curve were contrastively
      analyzed. A stepwise multivariate logistic regression was used for a
      multivariable analysis to determine the factors that affect the operative time
      using Huang 3-step maneuver. Based on the CUSUM, the learning curve for Huang 3
      step maneuver was divided into phase 1 (cases 1-40) and phase 2 (cases 41-130).
      The dissection time (DT) (P < 0.001), blood loss (BL) (P < 0.001), and number of
      vessels injured in phase 2 were significantly less than those in phase 1. There
      were no significant differences in the clinicopathological characteristics, short
      term outcomes, or major postoperative complications between the learning curve
      phases. Univariate and multivariate analyses revealed that body mass index (BMI),
      short gastric vessels (SGVs), splenic hilar artery (SpA) type, and learning curve
      phase were significantly associated with DT. In the entire group, 124 patients
      were followed for a median time of 23.0 months (range, 3-30 months). There was no
      significant difference in the survival curve between phases. AUGC patients with a
      BMI less than 25 kg/m2, a small number of SGVs, and a concentrated type of SpA
      are ideal candidates for surgeons who are in phase 1 of the learning curve.

PMID- 27043699
TI  - Acute Urinary Retention During Pregnancy--A Nationwide Population-Based Cohort
      Study in Taiwan.
AB  - The aim of the study was to investigate the epidemiology and risk factors of
      acute urinary retention (AUR) during pregnancy. We included all cases of
      pregnancies with AUR reported in Taiwan's Longitudinal Health Insurance Database
      from January 1, 1998, to December 31, 2011. Cases of AUR onset 1 day before
      delivery were excluded. The Cochrane-Armitage trend test and logistic regression
      analysis were used to evaluate the age distribution and types of deliveries of
      pregnant women. Chi-square tests and Fisher's exact test were performed to
      examine the association among all covariates. The odds ratios (OR) and 95%
      confidence intervals (CI) were estimated. We identified 308 cases of AUR in
      65,490 pregnancies. The risk of AUR during pregnancy was 0.47%. The peak
      incidence occurred between the 9th and 16th gestational weeks. Patients who
      experienced preterm delivery exhibited the highest risk for AUR (2.18%). Those
      with post-term delivery had the second highest risk (0.46%), and patients with a
      normal delivery exhibited the lowest risk (0.33%). Compared with normal delivery,
      preterm delivery carried a higher risk of AUR (OR: 6.33, 95% CI: 4.94-8.11). The
      AUR risk was higher for patients with advanced maternal age (>35 years old) than
      it was for those in the younger group (< 20 years old) (OR: 2.62, 95% CI: 1.18
      5.81). Within the normal delivery group, higher incidences of urogenital
      infection, gestational diabetes mellitus, previous abortion, abnormal pelvis,
      disproportion, and endometriosis were noted in women with AUR than in those
      without AUR (all P values <0.05). Women with advanced maternal age and those who
      experienced preterm delivery had an increased risk for AUR. The peak incidence of
      AUR in normal pregnancies occurred between the 9th and 16th gestational weeks.
      Urogenital infection, gestational diabetes mellitus, previous abortion, abnormal
      pelvis, disproportion, and endometriosis were associated with AUR in women who
      underwent a normal delivery.

PMID- 27043700
TI  - Effect of the Prolonged Inspiratory to Expiratory Ratio on Oxygenation and
      Respiratory Mechanics During Surgical Procedures.
AB  - Prolonged inspiratory to expiratory (I:E) ratio ventilation has been researched
      to reduce lung injury and improve oxygenation in surgical patients with one-lung
      ventilation (OLV) or carbon dioxide (CO2) pneumoperitoneum. We aimed to confirm
      the efficacy of the 1:1 equal ratio ventilation (ERV) compared with the 1:2
      conventional ratio ventilation (CRV) during surgical procedures. Electronic
      databases, including PubMed, Embase, Cochrane Central Register of Controlled
      Trials, Web of Science, and Google Scholar were searched.Prospective
      interventional trials that assessed the effects of prolonged I:E ratio of 1:1
      during surgical procedures. Adult patients undergoing OLV or CO2 pneumoperitoneum
      as specific interventions depending on surgical procedures. The included studies
      were examined with the Cochrane Collaboration's tool. The data regarding
      intraoperative oxygenation and respiratory mechanics were extracted, and then
      pooled with standardized mean difference (SMD) using the method of Hedges. Seven
      trials (498 total patients, 274 with ERV) were included. From overall analysis,
      ERV did not improve oxygenation at 20 or 30 minutes after specific interventions
      (SMD 0.193, 95% confidence interval (CI): -0.094 to 0.481, P = 0.188). From
      subgroup analyses, ERV provided significantly improved oxygenation only with
      laparoscopy (SMD 0.425, 95% CI: 0.167-0.682, P = 0.001). At 60 minutes after the
      specific interventions, ERV improved oxygenation significantly in the overall
      analysis (SMD 0.447, 95% CI: 0.209-0.685, P < 0.001) as well as in the subgroup
      analyses with OLV (SMD 0.328, 95% CI: 0.011-0.644, P = 0.042) and laparoscopy
      (SMD 0.668, 95% CI: 0.052-1.285, P = 0.034). ERV provided lower peak airway
      pressure (Ppeak) and plateau airway pressure (Pplat) than CRV, regardless of the
      type of intervention. The relatively small number of the included articles and
      their heterogeneity could be the main limitations. ERV improved oxygenation at
      all of the assessment points during laparoscopy. In OLV, oxygenation improvement
      with ERV was observed 1 hour after application. ERV could be beneficial to reduce
      the Ppeak and Pplat.

PMID- 27043701
TI  - Frequency-Specific Local Synchronization Changes in Paroxysmal Kinesigenic
      Dyskinesia.
AB  - The neurobiological basis of paroxysmal kinesigenic dyskinesia (PKD) is poorly
      defined due to the lack of reliable neuroimaging differences that can distinguish
      PKD with dystonia (PKD-D) from PKD with chorea (PKD-C). Consequently, diagnosis
      of PKD remains largely based on the clinical phenotype. Understanding the
      pathophysiology of PKD may facilitate discrimination between PKD-D and PKD-C,
      potentially contributing to more accurate diagnosis. We conducted resting-state
      functional magnetic resonance imaging on patients with PKD-D (n = 22), PKD-C (n =
      10), and healthy controls (n = 32). Local synchronization was measured in all 3
      groups via regional homogeneity (ReHo) and evaluated using receiver operator
      characteristic analysis to distinguish between PKD-C and PKD-D. Cortical-basal
      ganglia circuitry differed significantly between the 2 groups at a specific
      frequency. Furthermore, the PKD-D and PKD-C patients were observed to show
      different spontaneous brain activity in the right precuneus, right putamen, and
      right angular gyrus at the slow-5 frequency band (0.01-0.027 Hz). The frequency
      specific abnormal local synchronization between the 2 types of PKD offers new
      insights into the pathophysiology of this disorder to some extent.

PMID- 27043702
TI  - Errors in Text and Tables 2 and 3.

PMID- 27043703
TI  - Reversible cerebral vasoconstriction syndromes and primary angiitis of the
      central nervous system: clinical, imaging, and angiographic comparison.
AB  - Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the
      central nervous system (PACNS) are invariably considered in the differential
      diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis
      remains challenging. Here we compared the features of 159 RCVS to 47 PACNS
      patients and developed criteria for prompt bedside diagnosis. Recurrent
      thunderclap headache (TCH), and single TCH combined with either normal
      neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive
      predictive value for diagnosing RCVS or RCVS-spectrum disorders. In patients
      without TCH and positive angiography, neuroimaging can discriminate RCVS (no
      lesion) from PACNS (deep/brainstem infarcts). Ann Neurol 2016;79:882-894. 

PMID- 27043704
TI  - Modulating the generation of long-lived charge separated states exclusively from
      the triplet excited states in palladium porphyrin-fullerene conjugates.
AB  - This study demonstrates molecular engineering of a series of donor-acceptor
      systems to allow control of the lifetime and initial spin multiplicity of the
      charge-separated state. By tuning the rate of intersystem crossing (ISC) and the
      donor-acceptor distance, electron transfer can be made to occur exclusively from
      the triplet excited state of the electron donor resulting in long-lived charge
      separation. To achieve this, three new palladium porphyrin-fullerene donor
      acceptor systems were synthesized. The heavy Pd atom enhances the rate of ISC in
      the porphyrin and the rates of electron and energy transfer are modulated by
      varying the redox potential of the porphyrin and the porphyrin-fullerene
      distance. In the case of the meso-tris(tolyl)porphyrinato palladium(ii)
      fulleropyrrolidine, the donor-acceptor distance is relatively long (13.1 A) and
      the driving force for electron transfer is low. As a result, excitation of the
      porphyrin leads to rapid ISC followed by triplet-triplet energy transfer to
      fullerene. When the fullerene is bound directly to the porphyrin shortening the
      donor-acceptor distance to 2.6 A electron transfer from the singlet excited
      palladium porphyrin leading to the generation of a short-lived charge separated
      state is the main process. Finally, when the palladium porphyrin is substituted
      with three electron rich triphenylamine entities, the lower oxidation potential
      of the porphyrin and appropriate donor-acceptor distance (~13 A), lead to
      electron transfer exclusively from the triplet excited state of palladium
      porphyrin with high quantum yield. The results show that when electron transfer
      occurs from the triplet state, its increased lifetime allows the distance between
      the donor and acceptor to be increased which results in a longer lifetime for the
      charge separated state. 

PMID- 27043705
TI  - Sequential Ketene Generation from Dioxane-4,6-dione-keto-dioxinones for the
      Synthesis of Terpenoid Resorcylates.
AB  - Trapping of the ketene generated from the thermolysis of 2-methyl-2-phenyl-1,3
      dioxane-4,6-dione-keto-dioxinone at 50  degrees C with primary, secondary, or
      tertiary alcohols gave the corresponding dioxinone beta-keto-esters in good yield
      under neutral conditions. These intermediates were converted by palladium(0)
      catalyzed decarboxylative allyl migration and aromatization into the
      corresponding beta-resorcylates. These transformations were applied to the
      syntheses of the natural products (+/-)-cannabiorcichromenic and (+/-)
      daurichromenic acid. 

PMID- 27043706
TI  - Slow Relaxation of Surface Plasmon Excitations in Au55: The Key to Efficient
      Plasmonic Heating in Au/TiO2.
AB  - Gold nanoparticles distinguish themselves from other nanoparticles due to their
      unique surface plasmon resonance properties that can be exploited for a
      multiplicity of applications. The promise of plasmonic heating in systems of Au
      nanoparticles on transition metal oxide supports, for example, Au/TiO2, rests
      with the ability of the surface plasmon in Au nanoparticles to effectively
      transfer energy into the transition metal oxide. Here, we report a critical
      observation regarding Au nanoparticle (Au55) surface plasmon excitations, that
      is, the relaxation of the surface plasmon excitation is very slow, on the order
      of several picoseconds. Starting from five plasmon states in Au55 nanoparticles
      using nonadiabatic molecular dynamics simulations, we find that the relaxation
      time constant resulting from these simulations is ~6.8 ps, mainly resulting from
      a long-lived intermediate state found at around -0.8 eV. This long-lived
      intermediate state aligns with the conduction band edge of TiO2, thereby
      facilitating energy transfer injection from the Au55 nanoparticle into the TiO2.
      The current results rule out the previously reported molecular-like relaxation
      dynamics for Au55. 

PMID- 27043707
TI  - Increasing Partner Attendance in Antenatal Care and HIV Testing Services:
      Comparable Outcomes Using Written versus Verbal Invitations in an Urban Facility
      Based Controlled Intervention Trial in Mbeya, Tanzania.
AB  - In many Sub-Saharan African settings male partner involvement in antenatal care
      (ANC) remains low, although great benefits for maternal and infant health
      outcomes have been long recognised, in particular regarding the prevention of HIV
      transmission. Yet there is paucity on evidence regarding the effectiveness of
      strategies to increase male partner involvement. This controlled intervention
      trial in Ruanda Health Centre in Mbeya, Tanzania, assessed the effectiveness of
      invitation letters for male involvement in ANC. Pregnant women approaching ANC
      without partners received official letters inviting the partner to attend ANC. A
      control group was instructed to verbally invite partners. Partner attendance was
      recorded at two subsequent ANC visits. Rates for male partner return, couple
      voluntary counselling and testing (CVCT), and influencing factors were analysed.
      From 199 ANC clients in total, 97 were assigned to the invitation letter group;
      30 of these (30.9%) returned with their male partners for ANC. In the control
      group of 102 women, 28 (27.5%) returned with their partner. In both groups CVCT
      rates among jointly returning couples were 100%. Partner return/CVCT rate was not
      statistically different in intervention and control group (OR 1.2, p = 0.59).
      Former partner attendance at ANC during a previous pregnancy was the only factor
      found to be significantly linked with partner return (p = 0.03). Our study
      demonstrates that rather simple measures to increase male partner attendance in
      ANC and CVCT can be effective, with written and verbal invitations having
      comparable outcomes. In terms of practicability in Sub-Saharan African settings,
      we recommend systematic coaching of ANC clients on how to verbally invite male
      partners in the first instance, followed by written invitation letters for
      partners in case of their non-attendance. Further studies covering both urban and
      rural settings will be more informative for effective translation into policy. 

PMID- 27043708
TI  - Comparison of Visceral Fat Measures with Cardiometabolic Risk Factors in Healthy
      Adults.
AB  - We aimed to evaluate the associations of visceral adiposity with cardiometabolic
      risk factors in normal subjects with integrated 18F-Fluorodeoxyglucose (FDG)
      positron emission tomography (PET)/computed tomography (CT). A total of 58 normal
      subjects who underwent 18F-FDG PET/CT scan for cancer screening were included in
      this study. Volume and average Hounsfield unit (HU) of visceral adipose tissue
      (VAT) was measured from CT components of integrated PET/CT. Standardized uptake
      values (SUVmax) of liver, spleen, lumbar spine and ascending aorta (AA) were
      measured from PET components of integrated PET/CT. Body mass index (coefficient
      78.25, p = 0.0259), glucose (37.62, p<0.0001), insulin (348.90, p = 0.0011),
      logarithmic transformation of homeostatic model assessment index-insulin
      resistance (-2118.37, p = 0.0007), and VAT HU (-134.99, p<0.0001) were
      independently associated with VAT volume. Glucose (0.1187, p = 0.0098) and VAT
      volume (-0.004, p<0.0001) were found to be associated with VAT HU. Both VAT
      volume and VAT HU of whole abdominal cavity is significantly associated with
      cardiometabolic risk factors. 

PMID- 27043709
TI  - Prevalence and Sequence-Based Identity of Rumen Fluke in Cattle and Deer in New
      Caledonia.
AB  - An abattoir survey was performed in the French Melanesian archipelago of New
      Caledonia to determine the prevalence of paramphistomes in cattle and deer and to
      generate material for molecular typing at species and subspecies level.
      Prevalence in adult cattle was high at animal level (70% of 387 adult cattle) and
      batch level (81%). Prevalence was lower in calves at both levels (33% of 484
      calves, 51% at batch level). Animals from 2 of 7 deer farms were positive for
      rumen fluke, with animal-level prevalence of 41.4% (29/70) and 47.1% (33/70),
      respectively. Using ITS-2 sequencing, 3 species of paramphistomes were
      identified, i.e. Calicophoron calicophorum, Fischoederius elongatus and
      Orthocoelium streptocoelium. All three species were detected in cattle as well as
      deer, suggesting the possibility of rumen fluke transmission between the two host
      species. Based on heterogeneity in ITS-2 sequences, the C. calicophorum
      population comprises two clades, both of which occur in cattle as well as deer.
      The results suggest two distinct routes of rumen fluke introduction into this
      area. This approach has wider applicability for investigations of the origin of
      rumen fluke infections and for the possibility of parasite transmission at the
      livestock-wildlife interface. 

PMID- 27043710
TI  - Buffering and Amplifying Interactions among OAW (Ocean Acidification & Warming)
      and Nutrient Enrichment on Early Life-Stage Fucus vesiculosus L. (Phaeophyceae)
      and Their Carry Over Effects to Hypoxia Impact.
AB  - Ocean acidification and warming (OAW) are occurring globally. Additionally, at a
      more local scale the spreading of hypoxic conditions is promoted by
      eutrophication and warming. In the semi-enclosed brackish Baltic Sea, occasional
      upwelling in late summer and autumn may expose even shallow-water communities
      including the macroalga Fucus vesiculosus to particularly acidified, nutrient
      rich and oxygen-poor water bodies. During summer 2014 (July-September) sibling
      groups of early life-stage F. vesiculosus were exposed to OAW in the presence and
      absence of enhanced nutrient levels and, subsequently to a single upwelling event
      in a near-natural scenario which included all environmental fluctuations in the
      Kiel Fjord, southwestern Baltic Sea, Germany (54 degrees 27 'N, 10 degrees 11
      'W). We strove to elucidate the single and combined impacts of these potential
      stressors, and how stress sensitivity varies among genetically different sibling
      groups. Enhanced by a circumstantial natural heat wave, warming and acidification
      increased mortalities and reduced growth in F. vesiculosus germlings. This
      impact, however, was mitigated by enhanced nutrient conditions. Survival under
      OAW conditions strongly varied among sibling groups hinting at a substantial
      adaptive potential of the natural Fucus populations in the Western Baltic. A
      three-day experimental upwelling caused severe mortality of Fucus germlings,
      which was substantially more severe in those sibling groups which previously had
      been exposed to OAW. Our results show that global (OAW), regional (nutrient
      enrichment) and local pressures (upwelling), both alone and co-occurring may have
      synergistic and antagonistic effects on survival and/or growth of Fucus
      germlings. This result emphasizes the need to consider combined stress effects. 

PMID- 27043711
TI  - Highly Tactic Cyclic Polynorbornene: Stereoselective Ring Expansion Metathesis
      Polymerization of Norbornene Catalyzed by a New Tethered Tungsten-Alkylidene
      Catalyst.
AB  - The tungsten alkylidyne [(t)BuOCO]W=C((t)Bu) (THF)2 (1) reacts with CO2, leading
      to complete cleavage of one C?O bond, followed by migratory insertion to generate
      the tungsten-oxo alkylidene 2. Complex 2 is the first catalyst to polymerize
      norbornene via ring expansion metathesis polymerization to yield highly cis
      syndiotactic cyclic polynorbornene. 

PMID- 27043712
TI  - Indirect Reciprocity; A Field Experiment.
AB  - Indirect reciprocity involves cooperative acts towards strangers, either in
      response to their kindness to third parties (downstream) or after receiving
      kindness from others oneself (upstream). It is considered to be important for the
      evolution of cooperative behavior amongst humans. Though it has been widely
      studied theoretically, the empirical evidence of indirect reciprocity has thus
      far been limited and based solely on behavior in laboratory experiments. We
      provide evidence from an online environment where members can repeatedly ask and
      offer services to each other, free of charge. For the purpose of this study we
      created several new member profiles, which differ only in terms of their serving
      history. We then sent out a large number of service requests to different members
      from all over the world. We observe that a service request is more likely to be
      rewarded for those with a profile history of offering the service (to third
      parties) in the past. This provides clear evidence of (downstream) indirect
      reciprocity. We find no support for upstream indirect reciprocity (in this case,
      rewarding the service request after having previously received the service from
      third parties), however. Our evidence of downstream indirect reciprocity cannot
      be attributed to reputational effects concerning one's trustworthiness as a
      service user. 

PMID- 27043713
TI  - Large-Scale Biophysical Evaluation of Protein PEGylation Effects: In Vitro
      Properties of 61 Protein Entities.
AB  - PEGylation is the most widely used method to chemically modify protein
      biopharmaceuticals, but surprisingly limited public data is available on the
      biophysical effects of protein PEGylation. Here we report the first large-scale
      study, with site-specific mono-PEGylation of 15 different proteins and
      characterization of 61 entities in total using a common set of analytical
      methods. Predictions of molecular size were typically accurate in comparison with
      actual size determined by size-exclusion chromatography (SEC) or dynamic light
      scattering (DLS). In contrast, there was no universal trend regarding the effect
      of PEGylation on the thermal stability of a protein based on data generated by
      circular dichroism (CD), differential scanning calorimetry (DSC), or differential
      scanning fluorimetry (DSF). In addition, DSF was validated as a fast and
      inexpensive screening method for thermal unfolding studies of PEGylated proteins.
      Multivariate data analysis revealed clear trends in biophysical properties upon
      PEGylation for a subset of proteins, although no universal trends were found.
      Taken together, these findings are important in the consideration of biophysical
      methods and evaluation of second-generation biopharmaceutical drug candidates.

PMID- 27043714
TI  - Quantum confined colloidal nanorod heterostructures for solar-to-fuel conversion.
AB  - Solar energy conversion, particularly solar-driven chemical fuel formation, has
      been intensely studied in the past decades as a potential approach for renewable
      energy generation. Efficient solar-to-fuel conversion requires artificial
      photosynthetic systems with strong light absorption, long-lived charge separation
      and efficient catalysis. Colloidal quantum confined nanoheterostructures have
      emerged as promising materials for this application because of the ability to
      tailor their properties through size, shape and composition. In particular,
      colloidal one-dimensional (1D) semiconductor nanorods (NRs) offer the opportunity
      to simultaneously maintain quantum confinement in radial dimensions for tunable
      light absorptions and bulk like carrier transport in the axial direction for long
      distance charge separations. In addition, the versatile chemistry of colloidal
      NRs enables the formation of semiconductor heterojunctions (such as CdSe/CdS dot
      in-rod NRs) to separate photogenerated electron-hole pairs and deposition of
      metallic domains to accept charges and catalyze redox reactions. In this review,
      we summarize research progress on colloidal NR heterostructures and their
      applications for solar energy conversion, emphasizing mechanistic insights into
      the working principle of these systems gained from spectroscopic studies.
      Following a brief overview of synthesis of various NRs and heterostructures, we
      introduce their electronic structures and dynamics of exciton and carrier
      transport and interfacial transfer. We discuss how these exciton and carrier
      dynamics are controlled by their structures and provide key mechanistic
      understanding on their photocatalytic performance, including the photo-reduction
      of a redox mediator (methyl viologen) and light driven H2 generation. We discuss
      the solar-driven H2 generation mechanism, key efficiency limiting steps, and
      potential approaches for rational improvement in semiconductor NR/metal
      heterostructures (such as Pt tipped CdSe@CdS dot-in-rod NRs). Finally, we
      conclude by pointing out challenges to be addressed in future research.

PMID- 27043715
TI  - Mining metagenomic whole genome sequences revealed subdominant but constant
      Lactobacillus population in the human gut microbiota.
AB  - The genus Lactobacillus includes over 215 species that colonize plants, foods,
      sewage and the gastrointestinal tract (GIT) of humans and animals. In the GIT,
      Lactobacillus population can be made by true inhabitants or by bacteria
      occasionally ingested with fermented or spoiled foods, or with probiotics. This
      study longitudinally surveyed Lactobacillus species and strains in the feces of a
      healthy subject through whole genome sequencing (WGS) data-mining, in order to
      identify members of the permanent or transient populations. In three time-points
      (0, 670 and 700 d), 58 different species were identified, 16 of them being
      retrieved for the first time in human feces. L. rhamnosus, L. ruminis, L.
      delbrueckii, L. plantarum, L. casei and L. acidophilus were the most represented,
      with estimated amounts ranging between 6 and 8 Log (cells g(-1) ), while the
      other were detected at 4 or 5 Log (cells g(-1) ). 86 Lactobacillus strains
      belonging to 52 species were identified. 43 seemingly occupied the GIT as true
      residents, since were detected in a time span of almost 2 years in all the three
      samples or in 2 samples separated by 670 or 700 d. As a whole, a stable community
      of lactobacilli was disclosed, with wide and understudied biodiversity.

PMID- 27043716
TI  - Pharmacists' Perceptions of the Barriers and Facilitators to the Implementation
      of Clinical Pharmacy Key Performance Indicators.
AB  - BACKGROUND: In hospitals around the world, there has been no consensus regarding
      which clinical activities a pharmacist should focus on until recently. In 2011, a
      Canadian clinical pharmacy key performance indicator (cpKPI) collaborative was
      formed. The goal of the collaborative was to advance pharmacy practice in order
      to improve patient outcomes and enhance the quality of care provided to patients
      by hospital pharmacists. Following a literature review, which indicated that
      pharmacists can improve patient outcomes by carrying out specific activities, and
      an evidence-informed consensus process, a final set of eight cpKPIs were
      established. Canadian hospitals leading the cpKPI initiative are currently in the
      early stages of implementing these indicators. OBJECTIVE: To explore pharmacists'
      perceptions of the barriers and facilitators to the implementation of cpKPIs.
      METHODS: Clinical pharmacists employed by the Nova Scotia Health Authority were
      invited to participate in focus groups. Focus group discussions were audio
      recorded and transcribed, and data was analyzed using thematic analysis.
      FINDINGS: Three focus groups, including 26 pharmacists, were conducted in
      February 2015. Three major themes were identified. Resisting the change was
      comprised of documentation challenges, increased workload, practice environment
      constraints, and competing priorities. Embracing cpKPIs was composed of seeing
      the benefit, demonstrating value, and existing supports. Navigating the unknown
      was made up of quality versus quantity battle, and insights into the future.
      CONCLUSIONS: Although pharmacists were challenged by documentation and other
      changes associated with the implementation of cpKPIs, they demonstrated
      significant support for cpKPIs and were able to see benefits of the
      implementation. Pharmacists came up with suggestions for overcoming resistance
      associated with the implementation of cpKPIs and provided insights into the
      future of pharmacy practice. The identification of barriers and facilitators to
      cpKPI implementation will be used to inform the implementation process on a local
      and national level.

PMID- 27043717
TI  - Interpretation of Spectroscopic Markers of Hydrogen Bonds.
AB  - Quantum calculations are used to examine whether an AH???D H-bond is
      unambiguously verified by a downfield shift of the bridging proton's NMR signal
      or a red (or blue) shift of the AH stretching frequency in the IR spectrum. It is
      found that such IR band shifts will occur even if the two groups experience weak
      or no attractive force, or if they are drawn in so close together that their
      interaction is heavily repulsive. The mere presence of a proton-acceptor molecule
      can affect the chemical shielding of a position occupied by a protondonor by
      virtue of its electron density, even if there is no H-bond present. This density
      induced shielding is heavily dependent on position around the proton-acceptor
      atom, and varies from one group to another. Evidence of a hydrogen bond rests on
      the measurement of a proton deshielding in excess of what is caused purely by the
      presence of the proton acceptor species. 

PMID- 27043718
TI  - Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral
      cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic
      nuclear quantification.
AB  - BACKGROUND: The use of lymphatic vessel density as a predictor of occult lymph
      node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never
      been reported. METHODS: Staining of the specific lymphatic endothelial cells
      nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined
      by counting the number of positive cells in squamous cell carcinomas (SCCs) of
      the oral cavity and the oropharynx with clinically negative necks. Correlation
      with histopathological data was established. RESULTS: Peritumoral PROX1 lymphatic
      nuclear count significantly correlated with the detection of OLNM in multivariate
      analysis (p < .005). The sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) of this parameter was 60%, 95%, 85%,
      and 90%, respectively. CONCLUSION: Peritumoral PROX1 lymphatic nuclear count in
      primary SCCs of the oral cavity and the oropharynx allows accurate prediction of
      occult lymph node metastasis. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1407
      1415, 2016.

PMID- 27043719
TI  - Genetic and Environmental Influences on Parent-Child Conflict and Child
      Depression Through Late Adolescence.
AB  - Few studies have investigated potential gender differences in the genetic and
      environmental influences on the prospective associations between parent-child
      conflict and later depression, a notable gap given substantial gender differences
      in rates of depression and suggestive evidence of differences in the etiology of
      depression among females and males. To fill this gap, we evaluated whether the
      prospective relationship between parent-child conflict and major depressive
      disorder symptoms varied as a function of parent-child gender composition. A
      combined twin and adoption sample was used (53% female; 85% European ancestry),
      containing 1,627 adolescent sibling pairs (789 monozygotic twin pairs, 594
      dizygotic/full-biological pairs, 244 genetically unrelated pairs) with
      assessments at two time points in adolescence (approximate ages 15 and 18).
      Prospective associations between parent-child conflict and subsequent adolescent
      depression were explained predominately through common genetic influences for
      mother-daughter and mother-son pairs but less so for father-daughter and father
      son pairs. Results support the notion that processes of gene-environment
      correlation involved in the prospective associations between parent-child
      conflict, and later adolescent depression appear to be less relevant to father
      child relationships in comparison to mother-child relationships. Notably, results
      did not show that parent-child conflict was more relevant to the etiology of
      major depressive disorder (MDD) for girls than boys; gender differences in
      depression do not appear to be due to differences in the associations between
      parent-child conflict and child depression.

PMID- 27043720
TI  - Myocardial apoptosis in heart disease: does the emperor have clothes?
AB  - Since the discovery of a novel mechanism of cell death that differs from
      traditional necrosis, i.e., apoptosis, there have been numerous studies
      concluding that increased apoptosis augments myocardial infarction and heart
      failure and that limiting apoptosis protects the heart. Importantly, the vast
      majority of cells in the heart are non-myocytes with only roughly 30 % myocytes,
      yet almost the entire field studying apoptosis in the heart has disregarded non
      myocyte apoptosis, e.g., only 4.7 % of 423 studies on myocardial apoptosis in the
      past 3 years quantified non-myocyte apoptosis. Accordingly, we reviewed the
      history of apoptosis in the heart focusing first on myocyte apoptosis, followed
      by the history of non-myocyte apoptosis in myocardial infarction and heart
      failure. Apoptosis of several of the major non-myocyte cell types in the heart
      (cardiac fibroblasts, endothelial cells, vascular smooth muscle cells,
      macrophages and leukocytes) may actually be responsible for affecting the
      severity of myocardial infarction and heart failure. In summary, even though it
      is now known that the majority of apoptosis in the heart occurs in non-myocytes,
      very little work has been done to elucidate the mechanisms by which non-myocyte
      apoptosis might be responsible for the adverse effects of apoptosis in myocardial
      infarction and heart failure. The goal of this review is to provide an impetus
      for future work in this field on non-myocyte apoptosis that will be required for
      a better understanding of the role of apoptosis in the heart.

PMID- 27043721
TI  - Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of
      [(11)C]CO2.
AB  - Three new positron emission tomography (PET) radiotracers of interest to our
      functional neuroimaging and translational oncology programs have been prepared
      through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl
      cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular
      cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized
      through a tandem trapping of [(11)C]CO2 followed by an intermolecular
      cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4
      thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was
      synthesized through a HATU peptide coupling of an amino precursor with
      [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium
      bromide). All radiochemical syntheses are fully automated on commercial
      radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical
      yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced
      to rodent imaging studies and preliminary PET imaging results are also reported.

PMID- 27043722
TI  - Co-Assembly of Heparin and Polypeptide Hybrid Nanoparticles for Biomimetic
      Delivery and Anti-Thrombus Therapy.
AB  - Biomimetic delivery carriers using polypeptide/heparin hybrid nanoparticles that
      are adsorbed onto red blood cells for extended blood circulation time have been
      developed. This might open up an avenue to promote the innovations and advances
      of biomimetic, stimuli-responsive drug delivery, especially for the site-specific
      treatment of intravascular diseases such as thrombosis. 

PMID- 27043723
TI  - The influence of drought and heat stress on long-term carbon fluxes of bioenergy
      crops grown in the Midwestern USA.
AB  - Perennial grasses are promising feedstocks for bioenergy production in the
      Midwestern USA. Few experiments have addressed how drought influences their
      carbon fluxes and storage. This study provides a direct comparison of ecosystem
      scale measurements of carbon fluxes associated with miscanthus (Miscanthus *
      giganteus), switchgrass (Panicum virgatum), restored native prairie and maize
      (Zea mays)/soybean (Glycine max) ecosystems. The main objective of this study was
      to assess the influence of a naturally occurring drought during 2012 on key
      components of the carbon cycle and plant development relative to non-extreme
      years. The perennials reached full maturity 3-5 years after establishment.
      Miscanthus had the highest gross primary production (GPP) and lowest net
      ecosystem exchange (NEE) in 2012 followed by similar values for switchgrass and
      prairie, and the row crops had the lowest GPP and highest NEE. A post-drought
      effect was observed for miscanthus. Over the duration of the experiment,
      perennial ecosystems were carbon sinks, as indicated by negative net ecosystem
      carbon balance (NECB), while maize/soybean was a net carbon source. Our
      observations suggest that perennial ecosystems, and in particular miscanthus, can
      provide a high yield and a large potential for CO2 fixation even during drought,
      although drought may negatively influence carbon uptake in the following year,
      questioning the long-term consequence of its maintained productivity.

PMID- 27043724
TI  - Infantile Periocular Haemangioma: Optimising the Therapeutic Response.
AB  - Oral propranolol is now established as the first-line treatment for infantile
      haemangiomas, and used in up to 20 % of all cases. Propranolol use in infants is
      most commonly instigated in a controlled environment to monitor for potential
      serious adverse events such as hypoglycaemia and hypotension. Two test doses are
      recommended, the first one of 300 MUg/kg followed by 2-hourly monitoring. On the
      subsequent day, a further dose of 650 MUg/kg is administered with the same
      monitoring. A dose of 2 mg/kg divided into three is started from the next day.
      Parents/carers need to be warned of common adverse effects, of which disturbed
      sleep is the commonest. Treatment is recommended for up to a year to avoid
      rebound growth and the need to restart the treatment. 

PMID- 27043725
TI  - Reply to the Letter to the Editor: Complications of Total Hip Arthroplasty:
      Standardized List, Definitions, and Stratification Developed by the Hip Society.

PMID- 27043726
TI  - Letter to the Editor: Complications of Total Hip Arthroplasty: Standardized List,
      Definitions, and Stratification Developed by the Hip Society.

PMID- 27043727
TI  - Higher Frequency of Reoperation With a New Bicruciate-retaining Total Knee
      Arthroplasty.
AB  - BACKGROUND: With as many as 25% of patients reporting residual knee symptoms
      after primary total knee arthroplasty (TKA), alternative implant designs and
      surgical techniques have been proposed to further reduce these symptoms. There is
      growing evidence that retention of the anterior cruciate ligament (ACL) results
      in more natural knee kinematics; thus, implants with more normal joint mechanics
      could provide improved physical function postoperatively and reduce the amount of
      residual symptoms. Advancements in the bicruciate-retaining (BCR) TKA implant
      design have been made, and based on these, we wished to compare the BCR with a
      more traditional cruciate-retaining (CR) implant. QUESTIONS/PURPOSES: (1) Was
      there a difference in the risk of reoperation after primary TKA between BCR and
      CR implant designs? (2) Was there a difference in the radiographic findings of
      radiolucent lines (RLLs) between the implant designs? (3) Was there a difference
      in patient-reported and clinical outcomes between the two implant designs?
      METHODS: Between January 2013 and May 2014, two surgeons performed 475 primary
      TKAs. During this time, 78 (16%) of these were performed with BCR implants and
      294 (62%) with CR implants; the remainder were performed with anterior-stabilized
      or more constrained designs as a result of increased deformity and/or ligamentous
      deficiencies. During this period, the general indications for BCR TKA were
      arthritic knees with only slight to moderate deformity and sufficient ligamentous
      integrity of both the ACL and posterior cruciate ligament. The indications for CR
      TKA were similar other than these patients presented with a deficient ACL. A
      total of 66 (85%) of the BCR and 237 (81%) of the CR TKAs were available for
      followup at a minimum of 12 months or when reoperation occurred before 12 months
      (mean, 18 months; range, 2-32 months). With the numbers available, there were no
      differences between the groups in terms of age and sex, but the patients
      undergoing CR TKA had a greater mean body mass index (33 +/- 7 versus 31 +/- 5
      kg/m2, p = 0.032). The frequency of early reoperation was compared between the
      groups as were radiographic evidence of RLL, patient-reported outcomes, and knee
      range of motion (ROM). RESULTS: Knees in the BCR group had a higher frequency of
      all-cause revision (5% [three of 66] versus 1.3% [three of 237]; hazard ratio
      (HR), 7.44; 95% confidence interval [CI], 1.24-44.80; p = 0.028). Knees in the
      BCR group had a higher frequency of irrigation and debridement with component
      retention (HR, 0.07; 95% CI, 0.02-0.28; p < 0.001). No differences were found
      between groups for subsequent manipulation (HR, 0.34; 95% CI, 0.08-1.42; p =
      0.137). The proportion of RLLs was greater in the BCR group (HR, 2.93; 95% CI,
      1.62-5.32; p < 0.001) compared with the CR group. There were no differences
      between the groups in terms of the Physical Function Computerized Adaptive Test
      scores, Global10 scores or knee ROM outcomes. CONCLUSIONS: Preliminary short-term
      findings suggest the BCR implant has inferior survivorship and concerning
      radiographic findings when compared with a conventional CR implant with respect
      to complications after primary TKA. These findings raise concerns about the new
      BCR design; however, further randomized trials are necessary to determine
      superiority between alternative implant designs. LEVEL OF EVIDENCE: Level III,
      therapeutic study.

PMID- 27043728
TI  - Cervical spine injuries, mechanisms, stability and AIS scores from vertical
      loading applied to military environments.
AB  - PURPOSE: The purpose of this study was to determine injuries to osteo-ligamentous
      structures of cervical column, mechanisms, forces, severities and AIS scores from
      vertical accelerative loading. METHODS: Seven human cadaver head-neck complexes
      (56.9 +/- 9.5 years) were aligned based on seated the posture of military
      soldiers. Army combat helmets were used. Specimens were attached to a vertical
      accelerator to apply caudo-cephalad g-forces. They were accelerated with
      increasing insults. Intermittent palpation and radiography were done. A roof
      structure mimicking military vehicle interior was introduced after a series of
      tests and experiments were conducted following similar protocols. Upon injury
      detection, CT and dissection were done. Temporal force responses were extracted,
      peak forces and times of occurrence were obtained, injury severities were graded,
      and spine stability was determined. RESULTS: Injuries occurred in tests only when
      the roof structure was included. Responses were tri-phasic: initial thrust,
      secondary tensile, tertiary roof contact phases. Peak forces: 1364-4382 N,
      initial thrust, 165-169 N, secondary tensile, 868-3368 N tertiary helmet-head
      roof contact phases. Times of attainments: 5.3-9.6, 31.7-42.6, 55.0-70.8 ms.
      Injuries included fractures and joint disruptions. Multiple injuries occurred in
      all but one specimen. A majority of injury severities were AIS = 2. Spines were
      considered unstable in a majority of cases. CONCLUSIONS: Spine response was tri
      phasic. Injuries occurred in roof contact tests with the helmeted head-neck
      specimen. Multiplicity and unstable nature of AIS = 2 level injuries, albeit at
      lower severities, might predispose the spine to long-term accelerated
      degenerative changes. Clinical protocols should include a careful evaluation of
      sub-catastrophic injuries in military patients.

PMID- 27043729
TI  - Imaging of primary pediatric lymphoma of bone.
AB  - BACKGROUND: Primary pediatric bone lymphoma is a rare form of non-Hodgkin
      lymphoma. Unlike nodal forms of lymphoma, imaging abnormalities in lymphoma of
      bone do not resolve rapidly in conjunction with treatment and radiologic findings
      can remain abnormal for years, making it difficult to evaluate treatment
      response. OBJECTIVE: To evaluate the utility of imaging in assessment of patients
      with primary pediatric bone lymphoma. MATERIALS AND METHODS: At our institution
      between 2004 and 2013, six cases of pathology-proven primary pediatric bone
      lymphoma were diagnosed. Retrospective chart review was performed to assess
      imaging utilization. Our data were qualitatively compared with existing
      literature to construct an algorithm for imaging patients with primary lymphoma
      of bone. RESULTS: Imaging evaluation of patients with primary pediatric bone
      lymphoma was highly variable at our institution. Conventional imaging was
      routinely used to evaluate response to treatment, despite lack of appreciable
      osseous change. Imaging in the absence of symptoms did not alter clinical
      management. Only positron emission tomography CT (PET/CT) proved capable of
      demonstrating imaging changes from the pretreatment to the post-treatment scans
      that were consistent with the clinical response to treatment. CONCLUSION:
      Surveillance imaging is likely unnecessary in patients with a known diagnosis of
      pediatric lymphoma of bone. Pretreatment and post-treatment PET/CT is likely
      sufficient to assess response. There is little data to support the use of interim
      and surveillance PET/CT.

PMID- 27043730
TI  - MRI findings of post-traumatic subperiosteal hematoma of the iliac bone with
      resultant femoral nerve palsy in an adolescent boy.
AB  - Post-traumatic subperiosteal hematoma of the iliac bone may present insidiously
      without external evidence of bleeding or go undetected in the acute setting. In
      some cases, the patient may come to medical attention due to femoral nerve palsy
      rather than hip or groin pain. In this report, we describe a case of femoral
      nerve palsy caused by acute post-traumatic subperiosteal hematoma of the iliac
      bone using MRI to highlight the subperiosteal location. Anatomy of the femoral
      nerve is also discussed. 

PMID- 27043731
TI  - Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin
      labeling correlate with disease activity.
AB  - BACKGROUND: Leigh disease is a metabolic disorder of the mitochondrial
      respiratory chain culminating in symmetrical necrotizing lesions in the deep gray
      nuclei or brainstem. Apart from classic gliotic/necrotic lesions, small-vessel
      proliferation is also characteristic on histopathology. We have observed lesional
      hyperperfusion on arterial spin-labeling (ASL) sequence in children with Leigh
      disease. OBJECTIVE: In this cross-sectional analysis, we evaluated lesional ASL
      perfusion characteristics in children with Leigh syndrome. MATERIALS AND METHODS:
      We searched the imaging database from an academic children's hospital for
      "arterial spin labeling, perfusion, necrosis, lactate, and Leigh" to build a
      cohort of children for retrospective analysis. We reviewed each child's medical
      record to confirm a diagnosis of Leigh disease, excluding exams with artifact,
      technical limitations, and without ASL images. We evaluated the degree and extent
      of cerebral blood flow and relationship to brain lesions. Images were compared to
      normal exams from an aged-matche cohort. RESULTS: The database search yielded 45
      exams; 30 were excluded. We evaluated 15 exams from 8 children with Leigh disease
      and 15 age-matched normal exams. In general, Leigh brain perfusion ranged from
      hyperintense (n=10) to hypointense (n=5). Necrotic lesions appeared
      hypointense/hypoperfused. Active lesions with associated restricted diffusion
      demonstrated hyperperfusion. ASL perfusion patterns differed significantly from
      those on age-matched normal studies (P=<.0001). Disease activity positively
      correlated with cerebral deep gray nuclei hyperperfusion (P=0.0037) and lesion
      grade (P=0.0256). CONCLUSION: Children with Leigh disease have abnormal perfusion
      of brain lesions. Hyperperfusion can be found in active brain lesions, possibly
      associated with small-vessel proliferation characteristic of the disease.

PMID- 27043732
TI  - Assessing the Therapeutic Potential of Targeted Attentional Bias Modification for
      Insomnia Using Smartphone Delivery.

PMID- 27043733
TI  - Kinetics of Acid-Catalyzed Dehydration of Cyclic Hemiacetals in Organic Aerosol
      Particles in Equilibrium with Nitric Acid Vapor.
AB  - Previous studies have shown that 1,4-hydroxycarbonyls, which are often major
      products of the atmospheric oxidation of hydrocarbons, can undergo acid-catalyzed
      cyclization and dehydration in aerosol particles to form highly reactive
      unsaturated dihydrofurans. In this study the kinetics of dehydration of cyclic
      hemiacetals, the rate-limiting step in this process, was investigated in a series
      of environmental chamber experiments in which secondary organic aerosol (SOA)
      containing cyclic hemiacetals was formed from the reaction of n-pentadecane with
      OH radicals in dry air in the presence of HNO3. A particle beam mass spectrometer
      was used to monitor the formation and dehydration of cyclic hemiacetals in real
      time, and SOA and HNO3 were quantified in filter samples by gravimetric analysis
      and ion chromatography. Measured dehydration rate constants increased linearly
      with increasing concentration of HNO3 in the gas phase and in SOA, corresponding
      to catalytic rate constants of 0.27 h(-1) ppmv(-1) and 7.0 h(-1) M(-1),
      respectively. The measured Henry's law constant for partitioning of HNO3 into SOA
      was 3.7 * 10(4) M atm(-1), ~25% of the value for dissolution into water, and the
      acid dissociation constant was estimated to be <8 * 10(-4), at least a factor of
      10(4) less than that for HNO3 in water. The results indicate that HNO3 was only
      weakly dissociated in the SOA and that dehydration of cyclic hemiacetals was
      catalyzed by molecular HNO3 rather than by H(+). The Henry's law constant and
      kinetics relationships measured here can be used to improve mechanisms and models
      of SOA formation from the oxidation of hydrocarbons in dry air in the presence of
      NOx, which are conditions commonly used in laboratory studies. The fate of cyclic
      hemiacetals in the atmosphere, where the effects of higher relative humidity,
      organic/aqueous phase separation, and acid catalysis by molecular H2SO4 and/or
      H(+) are likely to be important, is discussed.

PMID- 27043734
TI  - Evaluation of the migration of chemicals from baby bottles under standardised and
      duration testing conditions.
AB  - After the prohibition of bisphenol-A-containing polycarbonate baby bottles in the
      European Union (EU), alternative materials, such as polypropylene,
      polyethersulphone, TritanTM copolyester, etc., have appeared on the market. Based
      on an initial screening and in vitro toxicity assessment, the most toxic
      migrating compounds were selected to be monitored and quantified using validated
      GC- and LC-QqQ-MS methods. The effect of several 'real-life-use conditions', such
      as microwave, sterilisation and dishwasher, on the migration of different
      contaminants was evaluated by means of duration tests. These results were
      compared with a reference treatment (filling five times with pre-heated simulant
      at 40 degrees C) and with the legal EU 'repetitive-use conditions' (three
      migrations, 2 h at 70 degrees C). Analysis of the third migration step of the EU
      repetitive-use conditions (which has to comply with the EU legislative migration
      limits) showed that several non-authorised compounds were observed in some baby
      bottles exceeding 10 ug kg(-1). However, all authorised compounds were detected
      well below their respective specific migration limits (SMLs). The reference
      experiment confirmed the migration of some of the compounds previously detected
      in the EU repetitive-use experiment, though at lower concentrations. Analysis of
      extracts from the microwave and dishwasher experiments showed a reduction in the
      migration during the duration tests. In general, the concentrations found were
      low and comparable with the reference experiment. Similar observations were made
      for the two sterilisation types: steam and cooking sterilisation. However, steam
      sterilisation seems to be more recommended for daily use of baby bottles, since
      it resulted in a lower release of substances afterwards. Repeated use of baby
      bottles under 'real-life' conditions showed no increase in the migration of
      investigated compounds and, after some time, the migration of these compounds
      even became negligible. 

PMID- 27043735
TI  - A Retrospective Study of Clinical Effects of Powdered Caffeine Exposures Reported
      to Three US Poison Control Centers.
AB  - INTRODUCTION: Anhydrous caffeine, often sold on the Internet as a powdered
      caffeine product, is sold as "pure caffeine" to be used as an additive to
      beverages and has also been used as an ingredient in energy supplement products.
      METHODS: This is a retrospective multiple-poison center chart review of calls
      regarding powdered caffeine to poison centers covering Oregon, Alaska, Guam,
      Washington, and Utah between January 1, 2013 and June 30, 2015. RESULTS: There
      were 40 calls to three poison centers over 30 months for powdered caffeine
      exposure. The majority of patients were over age 19 (52.5 %; 21/40) and male (70
      %; 28/40). Sixty percent (24/40) of the patients were symptomatic but only 10 %
      (4/40) required admission; 52.5 % (21/40) of the patient calls were for
      inadvertent overdose of powdered caffeine; one patient overdosed in a self-harm
      attempt. DISCUSSION: Powdered caffeine calls to three poison centers during a 30
      month study period were rare, and severe caffeine toxicity due to exposure was
      found in few patients. The majority of symptoms were reported after an
      inadvertent powdered caffeine overdose. CONCLUSIONS: An analysis of calls to
      three poison centers for powdered caffeine found that exposures were uncommon,
      but did result in toxicity, and highlighted that the lack of clear dosing
      instructions on product packaging may place patients at risk of inadvertent
      overdose.

PMID- 27043736
TI  - Modeling U-Shaped Exposure-Response Relationships for Agents that Demonstrate
      Toxicity Due to Both Excess and Deficiency.
AB  - Essential elements such as copper and manganese may demonstrate U-shaped exposure
      response relationships due to toxic responses occurring as a result of both
      excess and deficiency. Previous work on a copper toxicity database employed
      CatReg, a software program for categorical regression developed by the U.S.
      Environmental Protection Agency, to model copper excess and deficiency exposure
      response relationships separately. This analysis involved the use of a severity
      scoring system to place diverse toxic responses on a common severity scale,
      thereby allowing their inclusion in the same CatReg model. In this article, we
      present methods for simultaneously fitting excess and deficiency data in the form
      of a single U-shaped exposure-response curve, the minimum of which occurs at the
      exposure level that minimizes the probability of an adverse outcome due to either
      excess or deficiency (or both). We also present a closed-form expression for the
      point at which the exposure-response curves for excess and deficiency cross,
      corresponding to the exposure level at which the risk of an adverse outcome due
      to excess is equal to that for deficiency. The application of these methods is
      illustrated using the same copper toxicity database noted above. The use of these
      methods permits the analysis of all available exposure-response data from
      multiple studies expressing multiple endpoints due to both excess and deficiency.
      The exposure level corresponding to the minimum of this U-shaped curve, and the
      confidence limits around this exposure level, may be useful in establishing an
      acceptable range of exposures that minimize the overall risk associated with the
      agent of interest.

PMID- 27043737
TI  - Nanoliposomal irinotecan plus fluorouracil and folinic acid: a new treatment
      option in metastatic pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with half of
      patients diagnosed in the metastatic setting. Until recently, patients after
      progression on front-line gemcitabine-based regimen had no standard second-line
      option, although flouropyrimidine-based regimens were frequently used in this
      setting. Encapsulation of chemotherapeutics in liposomal formulation is an
      effective way of prolonging drug deposition thereby enhancing cytotoxic efficacy.
      In a large phase III randomized trial on metastatic PDAC patients who progressed
      after gemcitabine-based chemotherapy, a novel nanoliposome-encapsulated
      irinotecan (PEP02, MM-398, nal-IRI, Onivyde, Merrimack, Boston, US) plus
      fluorouracil and folinic acid demonstrated a significant survival advantage
      compared to fluorouracil and folinic acid alone. This pivotal study led to the
      recent FDA approval of nanoliposomal irinotecan in patients with metastatic PDAC.
      In this article, we will review the literature regarding existing treatment
      options for metastatic PDAC, focusing specifically on nanoliposomal irinotecan in
      the clinical setting and its future implication. 

PMID- 27043738
TI  - Sensitivity of MRI parameters within intervertebral discs to the severity of
      adolescent idiopathic scoliosis.
AB  - PURPOSE: To measure magnetic resonance imaging (MRI) parameters including
      relaxation times (T1 rho, T2 ), magnetization transfer (MT) and diffusion
      parameters (mean diffusivity [MD], fractional anisotropy [FA]) of intervertebral
      discs in adolescents with idiopathic scoliosis, and to investigate the
      sensitivity of these MR parameters to the severity of the spine deformities.
      MATERIALS AND METHODS: Thirteen patients with adolescent idiopathic scoliosis and
      three control volunteers with no history of spine disease underwent an MRI
      acquisition at 3T including the mapping of T1 rho, T2 , MT, MD, and FA. The
      apical zone included all discs within the scoliotic curve while the control zone
      was composed of other discs. The severity was analyzed through low (<32 degrees )
      versus high (>40 degrees ) Cobb angles. One-way analysis of variance (ANOVA) and
      agglomerative hierarchical clustering (AHC) were performed. RESULTS: Significant
      differences were found between the apical zone and the control zone for T2 (P =
      0.047), and between low and high Cobb angles for T2 (P = 0.014) and MT (P =
      0.002). AHC showed two distinct clusters, one with mainly low Cobb angles and one
      with mainly high Cobb angles, for the MRI parameters measured within the apical
      zone, with an accuracy of 0.9 and a Matthews correlation coefficient (MCC) of
      0.8. Within the control zone, the AHC showed no clear classification (accuracy of
      0.6 and MCC of 0.2). CONCLUSION: We successfully performed an in vivo
      multiparametric MRI investigation of young patients with adolescent idiopathic
      scoliosis. The MRI parameters measured within the intervertebral discs were found
      to be sensitive to intervertebral disc degeneration occurring with scoliosis and
      to the severity of scoliosis. J. Magn. Reson. Imaging 2016;44:1123-1131.

PMID- 27043739
TI  - Regionalization of Children's Surgery.

PMID- 27043740
TI  - Veterans Administration Liver Transplant Programs Perform as Well as Their
      Affiliated Academic Institutions.

PMID- 27043741
TI  - Surgical Outcomes: Shifting the Focus From Measurement to Improvement.

PMID- 27043742
TI  - Main-duct Intraductal Papillary Mucinous Neoplasm. High Cancer Risk in Duct
      Diameter of 5 to 9 mm.

PMID- 27043743
TI  - Dynamic Probabilistic Modeling of Environmental Emissions of Engineered
      Nanomaterials.
AB  - The need for an environmental risk assessment for engineered nanomaterials (ENM)
      necessitates the knowledge about their environmental concentrations. Despite
      significant advances in analytical methods, it is still not possible to measure
      the concentrations of ENM in natural systems. Material flow and environmental
      fate models have been used to provide predicted environmental concentrations.
      However, almost all current models are static and consider neither the rapid
      development of ENM production nor the fact that many ENM are entering an in-use
      stock and are released with a lag phase. Here we use dynamic probabilistic
      material flow modeling to predict the flows of four ENM (nano-TiO2, nano-ZnO,
      nano-Ag and CNT) to the environment and to quantify their amounts in (temporary)
      sinks such as the in-use stock and ("final") environmental sinks such as soil and
      sediment. Caused by the increase in production, the concentrations of all ENM in
      all compartments are increasing. Nano-TiO2 had far higher concentrations than the
      other three ENM. Sediment showed in our worst-case scenario concentrations
      ranging from 6.7 MUg/kg (CNT) to about 40 000 MUg/kg (nano-TiO2). In most cases
      the concentrations in waste incineration residues are at the "mg/kg" level. The
      flows to the environment that we provide will constitute the most accurate and
      reliable input of masses for environmental fate models which are using process
      based descriptions of the fate and behavior of ENM in natural systems and rely on
      accurate mass input parameters.

PMID- 27043745
TI  - A review of prednisolone prescribing for children with acute asthma in the UK.
AB  - INTRODUCTION: Worldwide asthma guidelines recommend short courses of oral
      prednisolone in children with acute exacerbations generating high prescription
      numbers. There is a paucity of evidence to inform the optimal dose and course
      duration. This has led to a variation in the recommendations for prednisolone
      prescribing. Our objective was to assess prednisolone prescribing practise for
      children with acute asthma in a representative sample of UK prescribers. METHODS:
      We developed an online questionnaire asking prescribers the prednisolone dosage,
      course duration and formulation used, whether they discussed oral prednisolone
      side effects with the family and at what child's age they changed from
      prescribing soluble to non-soluble formulations. This was sent to 1006 UK
      prescribers including Paediatric Respiratory Consultants, doctors in training,
      asthma nurses and General Practitioners. RESULTS: 200 complete responses were
      received (response rate 20%). The majority of surveyed prescribers follow the
      British National Formulary for Children recommendations on dosage rather than
      those included in the British Thoracic Society and the Scottish Intercollegiate
      Guidelines Network. Despite this, we highlighted a 4-fold variation in
      prednisolone dosages for acute asthma. The majority of prescribers chose 3 days
      as the course duration. High use of soluble formulations was highlighted.
      CONCLUSIONS: There is wide variation in the dose of prednisolone prescribed for
      children with acute asthma in the UK. This reflects a relative lack of evidence
      that needs addressing.

PMID- 27043744
TI  - From faces to hands: Changing visual input in the first two years.
AB  - Human development takes place in a social context. Two pervasive sources of
      social information are faces and hands. Here, we provide the first report of the
      visual frequency of faces and hands in the everyday scenes available to infants.
      These scenes were collected by having infants wear head cameras during
      unconstrained everyday activities. Our corpus of 143hours of infant-perspective
      scenes, collected from 34 infants aged 1month to 2years, was sampled for analysis
      at 1/5Hz. The major finding from this corpus is that the faces and hands of
      social partners are not equally available throughout the first two years of life.
      Instead, there is an earlier period of dense face input and a later period of
      dense hand input. At all ages, hands in these scenes were primarily in contact
      with objects and the spatio-temporal co-occurrence of hands and faces was greater
      than expected by chance. The orderliness of the shift from faces to hands
      suggests a principled transition in the contents of visual experiences and is
      discussed in terms of the role of developmental gates on the timing and
      statistics of visual experiences.

PMID- 27043746
TI  - Do Employees Leave Just Because They Can? Examining the Perceived Employability
      Turnover Intentions Relationship.
AB  - The relationship between perceived employability and turnover intentions seems
      much more complicated than what the common sense would suggest. Based on the
      reviewed literature, it was expected that job satisfaction, affective commitment,
      and perceived job security would moderate this relationship. Using a sample of
      working individuals from different occupations and sectors (N = 721), it was
      found that employees who perceived themselves as highly employable were more
      likely to have turnover intentions when their affective commitment was low and
      perceived job security was high; and the relationship was negative for employees
      with shorter tenures. Understanding the conditions under which perceived
      employability is associated with turnover intentions may help organizations
      design human resource policies that allow them to retain an educated and
      competent workforce. 

PMID- 27043747
TI  - Evaluation of a hybrid ion exchange-catalyst treatment technology for nitrate
      removal from drinking water.
AB  - Ion exchange (IX) is the most common approach to treating nitrate-contaminated
      drinking water sources, but the cost of salt to make regeneration brine, as well
      as the cost and environmental burden of waste brine disposal, are major
      disadvantages. A hybrid ion exchange-catalyst treatment system, in which waste
      brine is catalytically treated for reuse, shows promise for reducing costs and
      environmental burdens of the conventional IX system. An IX model with separate
      treatment and regeneration cycles was developed, and ion selectivity coefficients
      for each cycle were separately calibrated by fitting experimental data. Of note,
      selectivity coefficients for the regeneration cycle required fitting the second
      treatment cycle after incomplete resin regeneration. The calibrated and validated
      model was used to simulate many cycles of treatment and regeneration using the
      hybrid system. Simulated waste brines and a real brine obtained from a California
      utility were also evaluated for catalytic nitrate treatment in a packed-bed, flow
      through column with 0.5 wt%Pd-0.05 wt%In/activated carbon support (PdIn/AC).
      Consistent nitrate removal and no apparent catalyst deactivation were observed
      over 23 d (synthetic brine) and 45 d (real waste brine) of continuous-flow
      treatment. Ion exchange and catalyst results were used to evaluate treatment of 1
      billion gallons of nitrate-contaminated source water at a 0.5 MGD water treatment
      plant. Switching from a conventional IX system with a two bed volume regeneration
      to a hybrid system with the same regeneration length and sequencing batch
      catalytic reactor treatment would save 76% in salt cost. The results suggest the
      hybrid system has the potential to address the disadvantages of a conventional IX
      treatment systems.

PMID- 27043748
TI  - Geraniin ameliorates cisplatin-induced nephrotoxicity in mice.
AB  - Geraniin, an active compound isolated from Geranium sibiricum, has been reported
      to have antioxidant and anti-inflammatory activities. The aim of this study was
      to investigate the protective effects of geraniin against cisplatin (CP)-induced
      kidney injury in mice. Geraniin was administrated for three consecutive days
      following CP (20 mg/kg) injection. The results showed that geraniin inhibited CP
      induced kidney histopathologic changes, MDA, inflammatory cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production in
      kidney tissues. Geraniin also inhibited CP-induced blood urea nitrogen (BUN) and
      creatinine production. Meanwhile, the activities of superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-PX) decreased by CP were reversed by the
      treatment of geraniin. In addition, geraniin significantly inhibited CP-induced
      NF-kappaB activation in kidney tissues. Treatment of geraniin dosedependently
      upregulated the expression of Nrf2 and HO-1. The anticancer effects of CP were
      not affected by the treatment of geraniin. In conclusion, these results indicated
      that geraniin protected against CP-induced nephrotoxicity by inhibiting oxidative
      stress and inflammatory response. 

PMID- 27043749
TI  - Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated
      rat: decisive role of TNF-alpha, IL-1beta, COX-II and iNOS.
AB  - CONTEXT: Overdose of acetaminophen (APAP) is common in humans and is often
      associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows
      multiple pharmacological activities including antioxidant and anti-inflammatory
      potential. OBJECTIVE: To evaluate the possible mechanism of hepatoprotective
      activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of
      Withania somnifera roots. MATERIALS AND METHODS: Hepatotoxicity was induced by
      oral administration of APAP (750 mg/kg, p.o.) for 14 d. The control group
      received the vehicle. APAP-treated animals were given either silymarin (25 mg/kg)
      or graded doses of WRF (50, 100 and 200mg/kg) 2 h prior to APAP administration.
      Animals were killed on 15th day and blood and liver tissue samples were collected
      for the further analysis. RESULTS: In WRF-treated group, there was significant
      and dose-dependent (p < 0.01 and p < 0.001) decrease in serum bilirubin, ALP, AST
      and ALT levels with significant and dose-dependent (p < 0.01 and p < 0.001)
      increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and
      NO decreased significantly (p < 0.01) by WRF treatment. Up-regulated mRNA
      expression of TNF-alpha, IL-1beta, COX-II and iNOS was significantly down
      regulated (p < 0.001) by WRF. Histological alternations induced by APAP in liver
      were restored to near normality by WRF pretreatment. CONCLUSION: WRF may exert
      its hepatoprotective action by alleviating inflammatory and oxido-nitrosative
      stress via inhibition of TNF-alpha, IL-1beta, COX-II and iNOS.

PMID- 27043750
TI  - The AKT2 potassium channel mediates NaCl induced depolarization in the root of
      Arabidopsis thaliana.
AB  - Soil salinization is a major cause of plant stress, partly due to the
      physicochemical similarities between Na(+) and K(+). Na(+) ions compete with K(+)
      ions for their transport into root cells. However, the point of Na(+) entry
      remains unidentified. Here, I have applied the Electrical Penetration Graph as a
      method for whole plant electrophysiology in order to test if (a) root exposure to
      NaCl induces depolarization waves that propagate from root to shoot via the
      phloem, and if (b) the electrophysiological effects of root exposure to NaCl
      require expression of the potassium channels AKT1 and/or AKT2. The data suggest
      that AKT2 subunit containing K(+) channels mediate NaCl-induced depolarization of
      root cells, and that this depolarization does not propagate to leaves via the
      phloem. 

PMID- 27043751
TI  - Communication Is Part of the Cure: Improving Health Literacy.

PMID- 27043752
TI  - Advances in Health Literacy Research--and Meditations on a Tool Shed.

PMID- 27043753
TI  - Guiding Oncology Patients Through the Maze of Precision Medicine.
AB  - As the role of genomics in health care grows, patients increasingly require
      adequate genetic literacy to fully engage in their care. This study investigated
      a model for delivering consumer-friendly genetic information to improve
      understanding of precision medicine using health literacy and learning style
      principles. My Cancer Genome (MCG), a freely available cancer decision support
      tool, was used as a testbed. MCG content on a melanoma tumor mutation, BRAF
      V600E, was translated to a 6th-grade reading level, incorporating multiple
      learning modalities. A total of 90 patients and caregivers were recruited from a
      melanoma clinic at an academic medical center and randomized to 3 groups. Group A
      (control) received an exact copy of text from MCG. Group B was given the same
      content with hyperlinks to videos explaining key genetic concepts, identified and
      labeled by the team as knowledge pearls. Group C received the translated content
      with the knowledge pearls embedded. Changes in knowledge were measured through
      pre and post questionnaires. Group C showed the greatest improvement in
      knowledge. The study results demonstrate that providing information based on
      health literacy and learning style principles can improve patients' understanding
      of genetic concepts, thus increasing their likelihood of taking an active role in
      any decision making concerning their health. 

PMID- 27043754
TI  - Effects on Text Simplification: Evaluation of Splitting Up Noun Phrases.
AB  - To help increase health literacy, we are developing a text simplification tool
      that creates more accessible patient education materials. Tool development is
      guided by a data-driven feature analysis comparing simple and difficult text. In
      the present study, we focus on the common advice to split long noun phrases. Our
      previous corpus analysis showed that easier texts contained shorter noun phrases.
      Subsequently, we conducted a user study to measure the difficulty of sentences
      containing noun phrases of different lengths (2-gram, 3-gram, and 4-gram); noun
      phrases of different conditions (split or not); and, to simulate unknown terms,
      pseudowords (present or not). We gathered 35 evaluations for 30 sentences in each
      condition (3 * 2 * 2 conditions) on Amazon's Mechanical Turk (N = 12,600). We
      conducted a 3-way analysis of variance for perceived and actual difficulty.
      Splitting noun phrases had a positive effect on perceived difficulty but a
      negative effect on actual difficulty. The presence of pseudowords increased
      perceived and actual difficulty. Without pseudowords, longer noun phrases led to
      increased perceived and actual difficulty. A follow-up study using the phrases (N
      = 1,350) showed that measuring awkwardness may indicate when to split noun
      phrases. We conclude that splitting noun phrases benefits perceived difficulty
      but hurts actual difficulty when the phrasing becomes less natural.

PMID- 27043755
TI  - Evaluation, Modification, and Validation of Pictograms Depicting Medication
      Instructions in the Elderly.
AB  - Poor health literacy has been recognized as a limiting factor in the elderly's
      ability to comprehend written or verbal medication information and also to
      successfully adhere to medical regimens. The objective of this study was to
      validate a set of pictograms depicting medication instructions for use among the
      elderly to support health literacy. Elderly outpatients were recruited in 3
      community pharmacies in Canada. One-on-one structured interviews were conducted
      to assess comprehension of 76 pictograms from the International Pharmaceutical
      Federation. Comprehension was assessed using transparency testing and pictogram
      translucency, or the degree to which the pictogram represents the intended
      message. A total of 135 participants were enrolled in this study, and 76
      pictograms were assessed. A total of 50 pictograms achieved more than 67%
      comprehension. Pictograms depicting precautions and warnings against certain side
      effects were generally not well understood. Gender, age, and education level all
      had a significant impact on the interpretation scores of certain individual
      pictograms. When all pictograms were included, younger males had a significantly
      higher comprehension score than older females, and participants with a higher
      level of education provided significantly higher translucency scores. Even when
      pictograms reached the comprehension threshold set by the International
      Organization for Standardization in the general populations, only 50 of these
      pictograms achieved more than 67% comprehension among the elderly, confirming
      that validation in this subpopulation should be conducted prior to using specific
      pictograms. Accompanying pictograms with education about these pictograms and
      important counseling points remains extremely important. 

PMID- 27043756
TI  - Health Literacy and Weight Change in a Digital Health Intervention for Women: A
      Randomized Controlled Trial in Primary Care Practice.
AB  - In the United States, 90 million adults have low health literacy. An important
      public health challenge is developing obesity treatment interventions suitable
      for those with low health literacy. The objective of this study was to examine
      differences in sociodemographic and clinical characteristics as well as weight
      and intervention engagement outcomes by health literacy. We randomized 194
      participants to usual care or to the Shape Program intervention, a 12-month
      digital health treatment aimed at preventing weight gain among overweight and
      Class I obese Black women in primary care practice. We administered the Newest
      Vital Sign instrument to assess health literacy. More than half (55%) of
      participants had low health literacy, which was more common among those with
      fewer years of education and lower income. There was no effect of health literacy
      on 12-month weight change or on intervention engagement outcomes (completion of
      coaching calls and interactive voice response self-monitoring calls). Low health
      literacy did not preclude successful weight gain prevention in the Shape Program
      intervention. Goal-focused behavior change approaches like that used in Shape may
      be particularly helpful for treating and engaging populations with low health
      literacy. 

PMID- 27043757
TI  - Health Literacy and Access to Care.
AB  - Despite well-documented links between low health literacy, low rates of health
      insurance coverage, and poor health outcomes, there has been almost no research
      on the relationship between low health literacy and self-reported access to care.
      This study analyzed a large, nationally representative sample of community
      dwelling adults ages 50 and older to estimate the relationship between low health
      literacy and self-reported difficulty obtaining care. We found that individuals
      with low health literacy were significantly more likely than individuals with
      adequate health literacy to delay or forgo needed care or to report difficulty
      finding a provider, even after we controlled for other factors, including health
      insurance coverage, employment, race/ethnicity, poverty, and general cognitive
      function. They were also more likely to lack a usual source of care, although
      this result was only marginally significant after we controlled for other
      factors. The results show that in addition to any obstacles that low health
      literacy creates within the context of the clinical encounter, low health
      literacy also reduces the probability that people get in the door of the health
      care system in a timely way. 

PMID- 27043758
TI  - Health Literacy Teaching in U.S. Family Medicine Residency Programs: A National
      Survey.
AB  - Health care providers, including medical residents, often lack adequate knowledge
      and skills to work effectively with patients who have limited health literacy.
      Little is known about the degree to which medical residents are trained to
      communicate effectively with people who have limited health literacy. This study
      aimed to assess the status of health literacy training for physicians in U.S.
      family medicine residency programs. We conducted an online survey of residency
      directors at 444 U.S. family medicine residencies. Among 138 respondents (31%
      response rate), 58 programs (42%) reported teaching residents about health
      literacy as part of the required curriculum. Most instruction occurred during the
      1st year of training. Hours of instruction ranged from 2 to 5 during Years 1
      through 3. Skills-based training (e.g., plain language techniques) was taught by
      most programs. Not having access to a faculty authority on health literacy was
      strongly associated with lack of a required health literacy curriculum.
      Respondents overwhelmingly agreed that increasing health literacy training for
      medical students and residents would help improve residents' clinical skills.
      This study provides a baseline snapshot of health literacy curricula in U.S.
      family medicine residencies and likely overestimates the prevalence of such
      curricula. Additional studies are needed to determine the quality of health
      literacy instruction in U.S. family medicine residencies and the most effective
      methods for teaching residents about health literacy. 

PMID- 27043759
TI  - Relationships Between Health Literacy and Genomics-Related Knowledge, Self
      Efficacy, Perceived Importance, and Communication in a Medically Underserved
      Population.
AB  - The increasing importance of genomic information in clinical care heightens the
      need to examine how individuals understand, value, and communicate about this
      information. Based on a conceptual framework of genomics-related health literacy,
      we examined whether health literacy was related to knowledge, self-efficacy, and
      perceived importance of genetics and family health history (FHH) and
      communication about FHH in a medically underserved population. The analytic
      sample was composed of 624 patients at a primary care clinic in a large urban
      hospital. About half of the participants (47%) had limited health literacy; 55%
      had no education beyond high school, and 58% were Black. In multivariable models,
      limited health literacy was associated with lower genetic knowledge (beta = 
      0.55, SE = 0.10, p < .0001), lower awareness of FHH (odds ratio [OR] = 0.50, 95%
      confidence interval [CI; 0.28, 0.90], p = .020), and greater perceived importance
      of genetic information (OR = 1.95, 95% CI [1.27, 3.00], p = .0022) but lower
      perceived importance of FHH information (OR = 0.47, 95% CI [0.26, 0.86], p =
      .013) and more frequent communication with a doctor about FHH (OR = 2.02, 95% CI
      [1.27, 3.23], p = .0032). The findings highlight the importance of considering
      domains of genomics-related health literacy (e.g., knowledge, oral literacy) in
      developing educational strategies for genomic information. Health literacy
      research is essential to avoid increasing disparities in information and health
      outcomes as genomic information reaches more patients.

PMID- 27043760
TI  - Cancer Health Literacy Test-30-Spanish (CHLT-30-DKspa), a New Spanish-Language
      Version of the Cancer Health Literacy Test (CHLT-30) for Spanish-Speaking
      Latinos.
AB  - This article describes the adaptation and initial validation of the Cancer Health
      Literacy Test (CHLT) for Spanish speakers. A cross-sectional field test of the
      Spanish version of the CHLT (CHLT-30-DKspa) was conducted among healthy Latinos
      in Louisiana. Diagonally weighted least squares was used to confirm the factor
      structure. Item response analysis using 2-parameter logistic estimates was used
      to identify questions that may require modification to avoid bias. Cronbach's
      alpha coefficients estimated scale internal consistency reliability. Analysis of
      variance was used to test for significant differences in CHLT-30-DKspa scores by
      gender, origin, age and education. The mean CHLT-30-DKspa score (N = 400) was
      17.13 (range = 0-30, SD = 6.65). Results confirmed a unidimensional structure,
      chi(2)(405) = 461.55, p = .027, comparative fit index = .993, Tucker-Lewis index
      = .992, root mean square error of approximation = .0180. Cronbach's alpha was
      .88. Items Q1-High Calorie and Q15-Tumor Spread had the lowest item-scale
      correlations (.148 and .288, respectively) and standardized factor loadings (.152
      and .302, respectively). Items Q19-Smoking Risk, Q8-Palliative Care, and Q1-High
      Calorie had the highest item difficulty parameters (difficulty = 1.12, 1.21, and
      2.40, respectively). Results generally support the applicability of the CHLT-30
      DKspa for healthy Spanish-speaking populations, with the exception of 4 items
      that need to be deleted or revised and further studied: Q1, Q8, Q15, and Q19.

PMID- 27043762
TI  - Recent Advances in Dental Bleaching with Laser and LEDs.

PMID- 27043761
TI  - Chromosome aberrations determined by sFISH and G-banding in lymphocytes from
      workers with internal deposits of plutonium.
AB  - PURPOSE: To examine the influence of alpha-particle radiation exposure from
      internally deposited plutonium on chromosome aberration frequencies in peripheral
      blood lymphocytes of workers from the Sellafield nuclear facility, UK. MATERIALS
      AND METHODS: Chromosome aberration data from historical single colour
      fluorescence in situ hybridization (sFISH) and Giemsa banding (G-banding)
      analyses, together with more recent sFISH results, were assessed using common
      aberration analysis criteria and revised radiation dosimetry. The combined sFISH
      group comprised 29 men with a mean internal red bone marrow dose of 21.0 mGy and
      a mean external gamma-ray dose of 541 mGy. The G-banding group comprised 23 men
      with a mean internal red bone marrow dose of 23.0 mGy and a mean external gamma
      ray dose of 315 mGy. RESULTS: Observed translocation frequencies corresponded to
      expectations based on age and external gamma-ray dose with no need to postulate a
      contribution from alpha-particle irradiation of the red bone marrow by internally
      deposited plutonium. Frequencies of stable cells with complex aberrations,
      including insertions, were similar to those in a group of controls and a group of
      workers with external radiation exposure only, who were studied concurrently. In
      a similar comparison there is some suggestion of an increase in cells with
      unstable complex aberrations and this may reflect recent direct exposure to
      circulating lymphocytes. CONCLUSIONS: Reference to in vitro dose response data
      for the induction of stable aberrant cells by alpha-particle irradiation
      indicates that the low red bone marrow alpha-particle radiation doses received by
      the Sellafield workers would not result in a discernible increase in
      translocations, thus supporting the in vivo findings. Therefore, the greater risk
      from occupational radiation exposure of the bone marrow resulting in viable
      chromosomally aberrant cells comes from, in general, much larger gamma-ray
      exposure in comparison to alpha-particle exposure from plutonium.

PMID- 27043763
TI  - 3D printing of functional biomaterials for tissue engineering.
AB  - 3D printing is emerging as a powerful tool for tissue engineering by enabling 3D
      cell culture within complex 3D biomimetic architectures. This review discusses
      the prevailing 3D printing techniques and their most recent applications in
      building tissue constructs. The work associated with relatively well-known inkjet
      and extrusion-based bioprinting is presented with the latest advances in the
      fields. Emphasis is put on introducing two relatively new light-assisted
      bioprinting techniques, including digital light processing (DLP)-based
      bioprinting and laser based two photon polymerization (TPP) bioprinting. 3D
      bioprinting of vasculature network is particularly discussed for its foremost
      significance in maintaining tissue viability and promoting functional maturation.
      Limitations to current bioprinting approaches, as well as future directions of
      bioprinting functional tissues are also discussed.

PMID- 27043764
TI  - Tomosynthesis can facilitate accurate measurement of joint space width under the
      condition of the oblique incidence of X-rays in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Accurate evaluation of joint space width (JSW) is important in the
      assessment of rheumatoid arthritis (RA). In clinical radiography of bilateral
      hands, the oblique incidence of X-rays is unavoidable, which may cause
      perceptional or measurement error of JSW. The objective of this study was to
      examine whether tomosynthesis, a recently developed modality, can facilitate a
      more accurate evaluation of JSW than radiography under the condition of oblique
      incidence of X-rays. METHODS: We investigated quantitative errors derived from
      the oblique incidence of X-rays by imaging phantoms simulating various finger
      joint spaces using radiographs and tomosynthesis images. We then compared the
      qualitative results of the modified total Sharp score of a total of 320 joints
      from 20 patients with RA between these modalities. RESULTS: A quantitative error
      was prominent when the location of the phantom was shifted along the JSW
      direction. Modified total Sharp scores of tomosynthesis images were significantly
      higher than those of radiography, that is to say JSW was regarded as narrower in
      tomosynthesis than in radiography when finger joints were located where the
      oblique incidence of X-rays is expected in the JSW direction. CONCLUSION:
      Tomosynthesis can facilitate accurate evaluation of JSW in finger joints of
      patients with RA, even with oblique incidence of X-rays. ADVANCES IN KNOWLEDGE:
      Accurate evaluation of JSW is necessary for the management of patients with RA.
      Through phantom and clinical studies, we demonstrate that tomosynthesis may
      achieve more accurate evaluation of JSW.

PMID- 27043765
TI  - The relevance of body positioning and its training effect on badminton smash.
AB  - One of the dominant skills in badminton is the forehand overhead smash, which
      consists of 1/5 attacks during games. Empirical evidences show that one has to
      adjust the body position in relation to the coming shuttlecock to produce a
      powerful and accurate smash. Therefore, positioning is a fundamental aspect
      influencing smash quality. Unfortunately, a search of literature has shown that
      there is a dearth/lack of study on this fundamental aspect. The goals of this
      study were to determine the influence of positioning and training experience on
      smash quality in order to discover information that could help learn/acquire the
      skill. Using 3D motion capture and full-body biomechanical modelling, 14 skilled
      and 15 novice players were analysed. Results have revealed that the body
      positioning has direct influence on shuttlecock release angle and clearance
      height of the offensive player. The results also suggest that, for training the
      positioning of beginners, one could conduct a self-selected comfort position
      towards a statically hanged shuttlecock and then step one foot back - a practical
      reference marker for learning. As one gains experience through repetitive
      training, improved limbs' coordination would increase smash quality further. We
      hope our findings will benefit practitioners for developing effective training
      programmes for beginners.

PMID- 27043766
TI  - Measuring the height-to-height correlation function of corrugation in suspended
      graphene.
AB  - Nanocorrugation of 2D crystals is an important phenomenon since it affects their
      electronic and mechanical properties. The corrugation may have various sources;
      one of them is flexural phonons that, in particular, are responsible for the
      thermal conductivity of graphene. A study of corrugation of just the suspended
      graphene can reveal much of valuable information on the physics of this
      complicated phenomenon. At the same time, the suspended crystal nanorelief can
      hardly be measured directly because of high flexibility of the 2D crystal.
      Moreover, the relief portion related to rapid out-of-plane oscillations (flexural
      phonons) is also inaccessible by such measurements. Here we present a technique
      for measuring the Fourier components of the height-height correlation function
      H(q) of suspended graphene which includes the effect of flexural phonons. The
      technique is based on the analysis of electron diffraction patterns. The H(q) is
      measured in the range of wavevectors q~0.4-4.5nm(-1). At the upper limit of this
      range H(q) does follow the T/kappaq(4) law. So, we measured the value of
      suspended graphene bending rigidity kappa=1.2+/-0.4eV at ambient temperature
      T~300K. At intermediate wave vectors, H(q) follows a slightly weaker exponent
      than theoretically predicted q(-3.15) but is closer to the results of the
      molecular dynamics simulation. At low wave vectors, the dependence becomes even
      weaker, which may be a sign of influence of charge carriers on the dynamics of
      undulations longer than 10nm. The technique presented can be used for studying
      physics of flexural phonons in other 2D materials.

PMID- 27043767
TI  - Mapping the electrostatic potential of Au nanoparticles using hybrid electron
      holography.
AB  - Electron holography is a powerful technique for characterizing electrostatic
      potentials, charge distributions, electric and magnetic fields, strain
      distributions and semiconductor dopant distributions with sub-nm spatial
      resolution. Mapping internal electrostatic and magnetic fields within
      nanoparticles and other low-dimensional materials by TEM requires both high
      spatial resolution and high phase sensitivity. Carrying out such an analysis
      fully quantitatively is even more challenging, since artefacts such as dynamical
      electron scattering may strongly affect the measurement. In-line electron
      holography, one of the variants of electron holography, features high phase
      sensitivity at high spatial frequencies, but suffers from inefficient phase
      recovery at low spatial frequencies. Off-axis electron holography, in contrast,
      can recover low spatial frequency phase information much more reliably, but is
      less effective in retrieving phase information at high spatial frequencies when
      compared to in-line holography. We investigate gold nanoparticles using hybrid
      electron holography at both atomic-resolution and intermediate magnification.
      Hybrid electron holography is a novel technique that synergistically combines off
      axis and in-line electron holography, allowing the measurement of the complex
      wave function describing the scattered electrons with excellent signal-to-noise
      properties at both high and low spatial frequencies. The effect of dynamical
      electron scattering is minimized by beam tilt averaging.

PMID- 27043768
TI  - Fluorocoxib A loaded nanoparticles enable targeted visualization of
      cyclooxygenase-2 in inflammation and cancer.
AB  - Cyclooxygenase-2 (COX-2) is expressed in virtually all solid tumors and its
      overexpression is a hallmark of inflammation. Thus, it is a potentially powerful
      biomarker for the early clinical detection of inflammatory disease and human
      cancers. We report a reactive oxygen species (ROS) responsive micellar
      nanoparticle, PPS-b-POEGA, that solubilizes the first fluorescent COX-2-selective
      inhibitor fluorocoxib A (FA) for COX-2 visualization in vivo. Pharmacokinetics
      and biodistribution of FA-PPS-b-POEGA nanoparticles (FA-NPs) were assessed after
      a fully-aqueous intravenous (i.v.) administration in wild-type mice and revealed
      4-8 h post-injection as an optimal fluorescent imaging window. Carrageenan
      induced inflammation in the rat and mouse footpads and 1483 HNSCC tumor
      xenografts were successfully visualized by FA-NPs with fluorescence up to 10-fold
      higher than that of normal tissues. The targeted binding of the FA cargo was
      blocked by pretreatment with the COX-2 inhibitor indomethacin, confirming COX-2
      specific binding and local retention of FA at pathological sites. Our collective
      data indicate that FA-NPs are the first i.v.-ready FA formulation, provide high
      signal-to-noise in inflamed, premalignant, and malignant tissues, and will
      uniquely enable clinical translation of the poorly water-soluble FA compound.

PMID- 27043769
TI  - A nanosensor for in vivo selenol imaging based on the formation of Au-Se bonds.
AB  - Selenol is a key metabolite of Na2SeO3 and plays an important role in many
      physiological and pathological processes. The real-time monitoring of selenol is
      of scientific interest for understanding the anti-cancer mechanism of Na2SeO3.
      Based on selenol's ability to specifically break AuS bonds and form more stable
      AuSe bonds on the surfaces of gold nanoparticles (AuNPs), we developed a novel
      near-infrared fluorescent nanosensor (Cy5.5-peptide-AuNPs) for detecting selenol.
      The nanosensor exhibited rapid response to selenol with high selectivity and
      sensitivity, and it was successfully used to image changes in the selenol level
      in HepG2 cells during Na2SeO3-induced apoptosis. Moreover, in vivo fluorescence
      imaging of selenol was obtained from H22 tumor-bearing mice injected with both
      the nanosensor and sodium selenite. The results showed that the tumor cell
      apoptosis induced by Na2SeO3 is correlated with high-level of selenol under
      hypoxic conditions. We believe that this nanosensor could serve as a powerful
      tool for monitoring selenol and exploring the physiological function of selenol
      in a variety of physiological and pathological contexts and that the probe
      designed strategy will provide a new platform for research on relevant selenium
      chemistry. 

PMID- 27043770
TI  - Maximum likelihood estimation for N-mixture models.
AB  - The focus of this article is on the nature of the likelihood associated with N
      mixture models for repeated count data. It is shown that the infinite sum
      embedded in the likelihood associated with the Poisson mixing distribution can be
      expressed in terms of a hypergeometric function and, thence, in closed form. The
      resultant expression for the likelihood can be readily computed to a high degree
      of accuracy and is algebraically tractable. Specifically, the likelihood
      equations can be simplified to some advantage, the concentrated likelihood in the
      probability of detection formulated and problematic cases identified. The results
      are illustrated by means of a simulation study and a real world example. The
      study is extended to N-mixture models with a negative binomial mixing
      distribution and results similar to those for the Poisson case obtained. N
      mixture models with mixing distributions which accommodate excess zeros and,
      separately, with a beta-binomial distribution rather than a binomial used to
      model the intra-site counts are also investigated. However the results for these
      settings, while computationally attractive, do not provide insight into the
      nature of the maximum likelihood estimates.

PMID- 27043771
TI  - How do patients with chest pain access Emergency Department care?
AB  - BACKGROUND: It is important that patients with symptoms of acute coronary
      syndrome receive appropriate medical care as soon as possible. Little is known
      about the preadmission actions that patients with chest pain take before arrival
      at the Emergency Department (ED). OBJECTIVE: This study aimed to describe the
      actions of patients with chest pain or pressure after onset of symptoms. What is
      the first action following onset of symptoms? Who is the first lay or
      professional person to be contacted? Which steps are taken first? How is the
      patient transported to the hospital? METHODS: Consecutive patients, arriving at
      the ED of two large hospitals in Belgium, were asked additional questions during
      the initial assessment. RESULTS: Overall, 35% of 412 consecutive patients with
      chest pain admitted to the ED were diagnosed with acute coronary syndrome. A
      total of 57% contacted a GP between symptom onset and arrival at the ED. Only 32%
      of the patients were transported to the ED by ambulance, 16% drove themselves and
      52% arrived by other means of transport (by family, neighbour, GP, public
      transport). CONCLUSION: In Belgium, the GP is still the first professional to be
      contacted for most patients. Other patients initially rely on their partner,
      family or friends when symptoms emerge. Too often, patients with chest pain rely
      on other transport to get to the ED instead of calling the Emergency Medical
      Services. This study included only patients who ultimately attended the ED.

PMID- 27043772
TI  - A criteria-directed protocol for in-hospital triage of trauma patients.
AB  - OBJECTIVE: To better match hospital resources to patients' needs of trauma care,
      a protocol for facilitating in-hospital triage decisions was implemented at a
      Swedish level I trauma centre. In the protocol, physiological parameters,
      anatomical injuries and mechanism of injury were documented, and used to activate
      full or limited trauma team response. The aim of this study was to evaluate the
      efficacy of the criteria-directed protocol to determine in-hospital trauma triage
      in an emergency department. METHODS: Level of triage and triage rates were
      compared before and after implementation of the protocol. Overtriage and
      undertriage were assessed with injury severity score higher than 15 as the cutoff
      for defining major trauma. Medical records for undertriaged patients were
      retrospectively reviewed. RESULTS: In 2011, 78% of 1408 trauma team activations
      required full trauma response, with an overtriage rate of 74% and an undertriage
      rate of 7%. In 2013, after protocol implementation, 58% of 1466 trauma team
      activations required full trauma response. Overtriage was reduced to 52% and
      undertriage was increased to 10%. However, there were no preventable deaths in
      the undertriaged patients. CONCLUSION: A criteria-directed protocol for use in
      the emergency department was efficient in reducing overtriage rates without
      risking undertriaged patients' safety.

PMID- 27043773
TI  - Adolescent tracheal intubation in an adult urban emergency department: a
      retrospective, observational study.
AB  - OBJECTIVES: Tracheal intubation is the cornerstone of advanced emergency airway
      management in children and adults and there is good-quality data characterizing
      intubation in both groups. There are, however, few published studies on emergency
      tracheal intubation in adolescents. We carried out an observational study to
      characterize tracheal intubation in adolescents. METHODS: We analysed data from a
      previously collected Emergency Department Intubation Registry. We included all
      attempts at tracheal intubation performed in our adult emergency department
      between 1999 and 2011. We recorded the indication for intubation, the staff
      involved, the technique and drugs used, and the rates of successful intubation
      and adverse events. We classified patients into three age groups: 13-16 years
      (adolescent), 17-24 years (young adult) and at least 25 years (older adult).
      RESULTS: Trauma was the most common indication for intubation in adolescents, and
      rapid sequence induction was used in 88% of cases. Ninety-nine percent of
      tracheal intubations in adolescent patients were successful on the first or the
      second attempt, no adolescent underwent more than three attempts and none
      required a surgical airway. The initial intubation attempt in adolescents was
      more likely to be performed by an anaesthetist (P<0.005). The first attempt
      success rate was higher (P<0.01) and adverse event rate was lower (P<0.05) in
      adolescents than in adults. Hypotension was the only adverse event recorded in
      adolescents; this occurred in three patients (4.5%). CONCLUSION: Our findings
      suggest that the airway in adolescent patients can be managed successfully and
      safely in an adult emergency department where there is close collaboration
      between anaesthetists and emergency physicians.

PMID- 27043775
TI  - Mid-infrared spectroscopy for rapid assessment of soil properties after land use
      change from pastures to Eucalyptus globulus plantations.
AB  - There is an increasing demand for rapid and cost effective techniques to
      accurately measure the effects of land use change on soil properties. This study
      evaluated the ability of mid-infrared spectroscopy (MIRS) coupled with partial
      least squares regression (PLSR) to rapidly predict soil properties affected by
      land use change from agriculture (mainly pasture) to Eucalyptus globulus
      plantations in south-western Australia. We measured total organic carbon (TOC),
      total nitrogen (Total N), TOC/Total N (C/N ratio), microbial biomass carbon
      (MBC), microbial biomass nitrogen (MBN), and total phosphorus (Total P). The PLSR
      calibration models were developed using mid-infrared (MIR) spectra (4000 to 450
      cm(-1)) and square root transformed measured soil data (n = 180) from 23 paired
      pasture and E. globulus plantation sites representing the soils and climate of E.
      globulus plantation estates in south-western Australia. The calibration models
      for TOC, Total N, C/N ratio and Total P showed excellent correlations between
      measured and predicted data with coefficient of determination (R(2)) exceeding
      0.91 and minimum root-mean-square error (RMSE) of calibration [TOC (R(2) = 0.95,
      RMSE = 0.36), Total N (R(2) = 0.96, RMSE = 0.10), C/N ratio (R(2) = 0.92, RMSE =
      0.14) and Total P (R(2) = 0.91, RMSE = 0.06)]. The calibration models had
      reasonable predictions for MBC (R(2) = 0.66, RMSE = 0.07) and MBN (R(2) = 0.63,
      RMSE = 0.06). The calibrated models were validated using soils from 8 independent
      paired pasture and E. globulus sites (n = 64). The validated predictions were
      excellent for TOC (R(2) = 0.92, RMSE = 0.40) and Total N (R(2) = 0.91, RMSE =
      0.12), but less so for C/N ratio (R(2) = 0.80, RMSE = 0.35), MBC (R(2) = 0.70,
      RMSE = 0.08) and Total P (R(2) = 0.75, RMSE = 0.12). The results demonstrate the
      potential of MIRS-PLSR to rapidly, accurately and simultaneously determine
      several properties in land use change affected soils. 

PMID- 27043776
TI  - The influence of mPEG-PCL and mPEG-PLGA on encapsulation efficiency and drug
      loading of SN-38 NPs.
AB  - The influence of mPEG-PCL and mPEG-PLGA on encapsulation efficiency and drug
      loading of nanoparticles was very important. SN-38 NPs were prepared from a
      series of diblock copolymers: mPEG1000-PLGA2000, mPEG2000-PCLs, mPEG5000-PCLs,
      mPEG2000-PLGAs, and mPEG5000-PLGAs by the thin film-hydration method. The
      prepared nanoparticles were characterized by morphology, size, encapsulation
      efficiency, drug-loading, and in vitro release behavior. This experiment
      suggested that the encapsulation efficiency and drug-loading of SN-38 NPs were
      attained the maximum values when the ratio of hydrophilic to hydrophobic block
      was between 1:2 and 1:3.

PMID- 27043777
TI  - Are styrene oligomers in coastal sediments of an industrial area aryl hydrocarbon
      receptor agonists?
AB  - Effect-directed analysis (EDA) was performed to identify the major aryl
      hydrocarbon receptor (AhR) agonists in sediments collected from a highly
      industrialized area (Lake Shihwa, Korea). Great AhR-mediated potencies were found
      in fractions containing aromatic compounds with log Kow values of 5-8, and
      relatively great concentrations of styrene oligomers (SOs) and polycyclic
      aromatic hydrocarbons (PAHs) were detected in those fractions. Until now, there
      was little information on occurrences and toxic relative potencies (RePs) of SOs
      in coastal environments. In the present study; i) distributions and compositions,
      ii) AhR binding affinities, and iii) contributions of SOs to total AhR-mediated
      potencies were determined in coastal sediments. Elevated concentrations of 10 SOs
      were detected in sediments of inland creeks ranging from 61 to 740 ng g(-1) dry
      mass (dm), while lesser concentrations were found in inner (mean = 33 ng g(-1)
      dm) and outer regions (mean = 25 ng g(-1) dm) of the lake. Concentrations of PAHs
      in sediments were comparable to those of SOs. 2,4-diphenyl-1-butene (SD3) was the
      predominant SO analogue in sediments. SOs and PAHs were accumulated in sediments
      near sources, and could not be transported to remote regions due to their
      hydrophobicity. RePs of 3 SOs could be derived, which were 1000- to 10,000-fold
      less than that of one representative potent AhR active PAH, benzo[a]pyrene.
      Although concentrations of SOs in sediments were comparable to those of PAHs, the
      collective contribution of SOs to total AhR-mediated potencies were rather small
      (<1%), primarily due to their smaller RePs. Overall, the present study provides
      information on distributions and AhR binding affinities for SOs as baseline data
      for degradation products of polystyrene plastic in the coastal environment. 

PMID- 27043778
TI  - The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in
      Primary Hyperparathyroidism: An Observational Study.
AB  - BACKGROUND: The comparative effectiveness of surgical and medical treatments on
      fracture risk in primary hyperparathyroidism (PHPT) is unknown. OBJECTIVE: To
      measure the relationship of parathyroidectomy and bisphosphonates with skeletal
      outcomes in patients with PHPT. DESIGN: Retrospective cohort study. SETTING: An
      integrated health care delivery system. PARTICIPANTS: All enrollees with
      biochemically confirmed PHPT from 1995 to 2010. MEASUREMENTS: Bone mineral
      density (BMD) changes and fracture rate. RESULTS: In 2013 patients with serial
      bone density examinations, total hip BMD increased transiently in women with
      parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and
      declined progressively in both women and men without these treatments (-6.6% and 
      7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the
      absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who
      had parathyroidectomy and 85.5 events per 1000 patients treated with
      bisphosphonates compared with 55.9 events per 1000 patients without these
      treatments. The risk for any fracture at 10 years was 156.8 events per 1000
      patients who had parathyroidectomy and 302.5 events per 1000 patients treated
      with bisphosphonates compared with 206.1 events per 1000 patients without these
      treatments. In analyses stratified by baseline BMD status, parathyroidectomy was
      associated with reduced fracture risk in both osteopenic and osteoporotic
      patients, whereas bisphosphonates were associated with increased fracture risk in
      these patients. Parathyroidectomy was associated with fracture risk reduction in
      patients regardless of whether they satisfied criteria from consensus guidelines
      for surgery. LIMITATION: Retrospective study design and nonrandom treatment
      assignment. CONCLUSION: Parathyroidectomy was associated with reduced fracture
      risk, and bisphosphonate treatment was not superior to observation. PRIMARY
      FUNDING SOURCE: National Institute on Aging.

PMID- 27043779
TI  - Proximate Kitaev quantum spin liquid behaviour in a honeycomb magnet.
AB  - Quantum spin liquids (QSLs) are topological states of matter exhibiting
      remarkable properties such as the capacity to protect quantum information from
      decoherence. Whereas their featureless ground states have precluded their
      straightforward experimental identification, excited states are more revealing
      and particularly interesting owing to the emergence of fundamentally new
      excitations such as Majorana fermions. Ideal probes of these excitations are
      inelastic neutron scattering experiments. These we report here for a ruthenium
      based material, alpha-RuCl3, continuing a major search (so far concentrated on
      iridium materials) for realizations of the celebrated Kitaev honeycomb
      topological QSL. Our measurements confirm the requisite strong spin-orbit
      coupling and low-temperature magnetic order matching predictions proximate to the
      QSL. We find stacking faults, inherent to the highly two-dimensional nature of
      the material, resolve an outstanding puzzle. Crucially, dynamical response
      measurements above interlayer energy scales are naturally accounted for in terms
      of deconfinement physics expected for QSLs. Comparing these with recent dynamical
      calculations involving gauge flux excitations and Majorana fermions of the pure
      Kitaev model, we propose the excitation spectrum of alpha-RuCl3 as a prime
      candidate for fractionalized Kitaev physics.

PMID- 27043780
TI  - Proton conduction in crystalline and porous covalent organic frameworks.
AB  - Progress over the past decades in proton-conducting materials has generated a
      variety of polyelectrolytes and microporous polymers. However, most studies are
      still based on a preconception that large pores eventually cause simply flow of
      proton carriers rather than efficient conduction of proton ions, which precludes
      the exploration of large-pore polymers for proton transport. Here, we demonstrate
      proton conduction across mesoporous channels in a crystalline covalent organic
      framework. The frameworks are designed to constitute hexagonally aligned, dense,
      mesoporous channels that allow for loading of N-heterocyclic proton carriers. The
      frameworks achieve proton conductivities that are 2-4 orders of magnitude higher
      than those of microporous and non-porous polymers. Temperature-dependent and
      isotopic experiments revealed that the proton transport in these channels is
      controlled by a low-energy-barrier hopping mechanism. Our results reveal a
      platform based on porous covalent organic frameworks for proton conduction.

PMID- 27043781
TI  - Interfacial geometry dictates cancer cell tumorigenicity.
AB  - Within the heterogeneous architecture of tumour tissue there exists an elusive
      population of stem-like cells that are implicated in both recurrence and
      metastasis. Here, by using engineered extracellular matrices, we show that
      geometric features at the perimeter of tumour tissue will prime a population of
      cells with a stem-cell-like phenotype. These cells show characteristics of cancer
      stem cells in vitro, as well as enhanced tumorigenicity in murine models of
      primary tumour growth and pulmonary metastases. We also show that interfacial
      geometry modulates cell shape, adhesion through integrin alpha5beta1, MAPK and
      STAT activity, and initiation of pluripotency signalling. Our results for several
      human cancer cell lines suggest that interfacial geometry triggers a general
      mechanism for the regulation of cancer-cell state. Similar to how a growing
      tumour can co-opt normal soluble signalling pathways, our findings demonstrate
      how cancer can also exploit geometry to orchestrate oncogenesis.

PMID- 27043782
TI  - Confined linear carbon chains as a route to bulk carbyne.
AB  - Strong chemical activity and extreme instability in ambient conditions
      characterize carbyne, an infinite sp(1) hybridized carbon chain. As a result,
      much less has been explored about carbyne as compared to other carbon allotropes
      such as fullerenes, nanotubes and graphene. Although end-capping groups can be
      used to stabilize carbon chains, length limitations are still a barrier for
      production, and even more so for application. We report a method for the bulk
      production of long acetylenic linear carbon chains protected by thin double
      walled carbon nanotubes. The synthesis of very long arrangements is confirmed by
      a combination of transmission electron microscopy, X-ray diffraction and (near
      field) resonance Raman spectroscopy. Our results establish a route for the bulk
      production of exceptionally long and stable chains composed of more than 6,000
      carbon atoms, representing an elegant forerunner towards the final goal of
      carbyne's bulk production.

PMID- 27043783
TI  - Effect of Combined Treatment Using Wilfortrine and Paclitaxel in Liver Cancer and
      Related Mechanism.
AB  - BACKGROUND: Liver cancer is a common malignant tumor with high mortality.
      Currently, effective medicines against liver cancer are still lacking. Paclitaxel
      is a wide-spectrum anti-tumor agent, while wilfortrine has been shown to have an
      inhibitory effect on the proliferation of liver cancer cells. This study thus
      investigated the potential effect of paclitaxel combined with wilfortrine on
      cultured liver cancer cells and related mechanisms, in order to provide evidence
      for pathogenesis and treatment of liver cancer. MATERIAL/METHODS: Liver cancer
      cell line HpeG2 was divided into control, paclitaxel, wilfortrine, and combined
      treatment groups. Cell proliferation was tested by MTT, while invasion was
      detected in Transwell chamber assay. Apoptotic protein Bcl-2 and Bax expression
      levels were further quantified using real-time PCR and Western blotting. RESULTS:
      Both of those 2 drugs can effectively inhibit cancer cell proliferation, depress
      invasion ability, increase Bcl-2 expression, and elevate Bax expression levels
      (p<0.05 in all cases). The combined therapy had better treatment efficacy
      compared to either of those drugs alone (p<0.05). CONCLUSIONS: The combined
      treatment using wilfortrine and paclitaxel can inhibit proliferation and invasion
      of liver cancer cells via down-regulating Bcl-2 and up-regulating Bax, with
      better efficacy than single use of either drug.

PMID- 27043784
TI  - Large-Animal Biventricular Working Heart Perfusion System with Low Priming Volume
      Comparison between in vivo and ex vivo Cardiac Function.
AB  - BACKGROUND: Existing large-animal, ex vivo, cardiac perfusion models are
      restricted in their ability to establish an ischemia/reperfusion condition as
      seen in cardiac surgery or transplantation. Other working heart systems only
      challenge one ventricle or require a substantially larger priming volume. We
      describe a novel biventricular cardiac perfusion system with reduced priming
      volume. METHODS: Juvenile pig hearts were cardiopleged, explanted, and reperfused
      ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as
      perfusate (minimal priming volume 350 mL). After 15 minutes of Langendorff
      perfusion (LM), the system was switched into a biventricular working mode (WM)
      and studied for 3 hours. RESULTS: During reperfusion, complete unloading of both
      ventricles and constant-pressure coronary perfusion was achieved. During working
      mode perfusion, the preload and afterload pressure of both ventricles was
      controlled within the targeted physiologic range. Functional parameters such as
      left ventricular work index were reduced in ex vivo working mode (in vivo: 787 +/
      186 vs. 1 h WM 498 +/- 66 mm Hg.mL/g.min; p < 0.01), but remained stable
      throughout the following study period (3 h WM 517 +/- 103 mm Hg.mL/g.min; p =
      0.63). Along with the elevated workload during WM, myocardial metabolism and
      oxygen consumption increased compared with LM (0.021 +/- 0.08 vs. 0.06 +/- 0.01
      mL/min/g; 1 h after reperfusion). Histologic examination of the myocardium
      revealed no structural damage. CONCLUSION: In the ex vivo perfusion system,
      stable hemodynamic and metabolic conditions can be established for a period of 3
      hours while functional and blood parameters are easily accessible. Moreover,
      because of the minimal priming volume, the novel ex vivo cardiac perfusion
      circuit allows for autologous perfusion, using the limited amount of blood
      available from the organ donating animal.

PMID- 27043785
TI  - The Beneficial Effect of Hypnosis in Elective Cardiac Surgery: A Preliminary
      Study.
AB  - Background Single-session hypnosis has never been evaluated as a premedication
      technique in patients undergoing coronary artery bypass grafting (CABG). The aim
      of the present study was to evaluate the beneficial effects of clinical
      hypnotherapy on perioperative anxiety, pain perception, sedation, and necessity
      for ventilator assistance in patients undergoing CABG. Methods Double-blind,
      randomized, clinical trial was performed. Forty-four patients undergoing CABG
      surgery were randomized into two groups. The patients in group A received
      preprocedural hypnosis by an anesthesiologist. Patients in group B (control) had
      only information on the surgical intervention by the same anesthesiologist. State
      Trait-Anxiety Index-I (STAI-I) and Beck Depression Inventory (BDI) were performed
      preoperatively in both groups. Visual analog scale (VAS) and Ramsay sedation
      scale (RSS) were evaluated on 0th, 1st, 2nd, 4th, 6th, 8th, 10th, 12th, and 24th
      hours, postoperatively. Postoperative anxiety level, analgesic drug consumption,
      and duration of ventilator assistance and intensive care unit (ICU) stay were
      also documented. Results When anxiety and depression levels were compared,
      significantly lower STA-I and BDI values were detected in group A after
      hypnotherapy (p = 0.001, p = 0.001, respectively). Significantly less total doses
      of remifentanil (34.4 +/- 11.4 vs. 50.0 +/- 13.6 mg) and morphine (4.9 +/- 3.3
      vs. 13.6 +/- 2.7 mg) were administered in group A in the postoperative period.
      Ventilator assistance duration (6.8 +/- 2.0 vs. 8.9 +/- 2.7 hours) was also
      shorter in group A when compared with that in group B (p = 0.007). Conclusion
      Hypnosis session prior to surgery was an effective complementary method in
      decreasing presurgical anxiety, and it resulted in better pain control as well as
      reduced ventilator assistance following CABG surgery.

PMID- 27043786
TI  - Plantar Sweating as an Indicator of Lower Risk of Compensatory Sweating after
      Thoracic Sympathectomy.
AB  - Background Hyperhidrosis is a dysfunction of the autonomic nervous system that
      results in regional excessive sweating, mostly in the hands, armpits, and feet. A
      permanent and effective treatment of hyperhidrosis can be achieved by
      interruption of the thoracic sympathetic chain with endoscopic thoracic
      sympathectomy (ETS). However, some side effects, particularly compensatory
      sweating (CS), are the limitations of this procedure. The mechanism of CS and the
      associated risk factors are still controversial. The aim of this retrospective
      study was to determine the relationship with various parameters associated with
      CS in patients undergoing ETS. Materials and Methods ETS was performed on a total
      of 95 patients for palmar hyperhidrosis, axillary hyperhidrosis and facial
      blushing by the same surgeon. The mean age of the patients was 26.41 (+/- 7)
      years, and 54 (56.8%) were males. Palmar hyperhidrosis was present in 54 (56.8%)
      patients, axillary hyperhidrosis in 33 (34.7%) patients, and facial blushing in 8
      (8.5%) patients. Moreover, 38 (40%) patients also had plantar sweating. The
      severity of CS was rated into three scales as less, moderate, and severe. Results
      Regarding the severity of CS, 55 (57.9%) patients had no or less CS, 28 (29.5%)
      had moderate CS, and 12 (12.6%) patients had severe CS. Higher age group had a
      significant increased risk of severe CS (p = 0.03) (r = 0.262). Patients with
      body mass index (BMI) > 25 kg/m2 had a statistically significantly increased risk
      of severe CS (p = 0.016). Facial blushing resulted in severe CS in a
      significantly higher proportion of patients than by palmar and axillary
      hyperhidrosis (p = 0.001). The level of surgery was another important risk factor
      for CS, with the T2 level showing an increased risk of severe CS compared with T3
      level (p < 0.001). Furthermore, plantar sweating was inversely and significantly
      related to the development of CS. Patients with plantar sweating had a
      significantly decreased incidence of developing CS (p = 0.015). Conclusion CS
      after thoracic sympathectomy for primary hyperhidrosis is the most displeasing
      and restrictive side effect. This study demonstrates that older age, operation
      level, facial blushing, and high BMI are risk factors for CS, as have been shown
      in several similar studies. An interesting finding of the present study is that
      there was a decreased incidence of CS among patients with plantar sweating. This
      situation may help us to distinguish high risk for CS before ETS operation.

PMID- 27043787
TI  - Application of Continuous Wound-Infusion Catheters in Lung Transplantation: A
      Retrospective Data Analysis.
AB  - Background Lung transplantation is the only treatment option for many patients
      with end-stage pulmonary disease. Therefore, postthoracotomy pain therapy is of
      vital interest. Thoracic epidural analgesia (EPI) is the "gold standard" for
      postthoracotomy pain, but especially in lung transplantation contraindications,
      and potential infectious complications limit its advantages. Under these
      circumstances surgically placed postthoracotomy catheter-assisted continuous
      paravertebral intercostal nerve block (PVB) could be of advantage. Methods We
      performed a retrospective cohort study of patients who underwent lung
      transplantation between 2005 and 2012. Groups were defined according to the type
      of postoperative pain therapy: PVB, EPI, and SYS (systemic analgesia). Total 44
      patients were eligible. Results Postoperative opioid requirement of the PVB and
      EPI group was comparable and less than that of the SYS group. Patients of the PVB
      group were weaned earlier from mechanical ventilation after lung transplantation.
      Conclusion The potency of postoperative pain therapy of EPI and PVB seemed to be
      comparable and superior to SYS. Considering the risks and benefits, PVB could be
      a better choice than EPI for postthoracotomy pain therapy, especially in lung
      transplantation.

PMID- 27043774
TI  - Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure.
AB  - BACKGROUND: Among patients with chronic heart failure, angiotensin-converting
      enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a
      renin inhibitor in such patients is unknown. We compared the ACE inhibitor
      enalapril with the renin inhibitor aliskiren (to test superiority or at least
      noninferiority) and with the combination of the two treatments (to test
      superiority) in patients with heart failure and a reduced ejection fraction.
      METHODS: After a single-blind run-in period, we assigned patients, in a double
      blind fashion, to one of three groups: 2336 patients were assigned to receive
      enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a
      dose of 300 mg once daily, and 2340 to receive both treatments (combination
      therapy). The primary composite outcome was death from cardiovascular causes or
      hospitalization for heart failure. RESULTS: After a median follow-up of 36.6
      months, the primary outcome occurred in 770 patients (32.9%) in the combination
      therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95%
      confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791
      patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95%
      CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There
      was a higher risk of hypotensive symptoms in the combination-therapy group than
      in the enalapril group (13.8% vs. 11.0%, P=0.005), as well as higher risks of an
      elevated serum creatinine level (4.1% vs. 2.7%, P=0.009) and an elevated
      potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS: In patients with chronic
      heart failure, the addition of aliskiren to enalapril led to more adverse events
      without an increase in benefit. Noninferiority was not shown for aliskiren as
      compared with enalapril. (Funded by Novartis; ATMOSPHERE ClinicalTrials.gov
      number, NCT00853658.).

PMID- 27043788
TI  - Assessing the Diagnostic Properties of a Graded Oral Provocation Challenge for
      the Diagnosis of Immediate and Nonimmediate Reactions to Amoxicillin in Children.
AB  - IMPORTANCE: The diagnostic properties of a graded provocation challenge (PC)
      among children presenting with a rash in the course of amoxicillin treatment are
      currently unknown. OBJECTIVE: To assess the accuracy and the negative predictive
      value of the PC in a cohort of children referred with suspected allergy to
      amoxicillin. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted
      between March 1, 2012, and April 1, 2015, at the allergy clinic of the Montreal
      Children's Hospital, Montreal, Quebec, Canada. All children referred with
      suspected allergy to amoxicillin were approached. In addition, 346 eligible
      children were followed up to assess reactions to subsequent use of amoxicillin at
      the time of illness in cases with negative PC results. Data were collected on
      clinical characteristics, suspected antibiotic exposure, personal and first
      degree relatives' comorbidities, and history of atopy and management of the
      reaction. Univariate and multivariate logistic regressions were compared to
      determine factors associated with immediate and nonimmediate reactions to the PC.
      INTERVENTIONS: All children had a graded PC. MAIN OUTCOMES AND MEASURES:
      Reactions to the graded PC, the negative predictive value of the PC for
      nonimmediate reactions, and factors associated with immediate and nonimmediate
      reactions to the PC. RESULTS: A total of 818 children were assessed (median age,
      1.7 years [interquartile range, 1.0-3.9 years]; 441 [53.9%] male). Among all
      participants, 770 (94.1%) tolerated the PC, 17 (2.1%) developed mild immediate
      reactions, and 31 (3.8%) developed nonimmediate reactions. The graded PC had a
      specificity of 100.0% (95% CI, 90.9%-100.0%), a negative predictive value of
      89.1% (95% CI, 77.1%-95.5%), and a positive predictive value of 100.0% (95% CI,
      86.3%-100.0%). Among all 346 participants eligible for annual follow-up, 250
      (72.3%; 95% CI, 67.2%-76.8%) responded, 55 of whom received subsequent full
      treatment with amoxicillin; 49 of these 55 participants (89.1%) reported
      tolerance to subsequent full treatment with amoxicillin, while 6 (10.9%)
      developed nonimmediate cutaneous reactions. History of a reaction occurring
      within 5 minutes of exposure was associated with immediate reactions to the PC
      (adjusted odds ratio = 9.6; 95% CI, 1.5-64.0), while a rash that lasted longer
      than 7 days (adjusted odds ratio = 4.8; 95% CI, 1.4-16.4) and parental history of
      drug allergy (adjusted odds ratio = 3.0; 95% CI, 1.3-6.8) were associated with
      nonimmediate reactions to the PC. CONCLUSIONS AND RELEVANCE: Graded PCs provide
      an accurate and safe confirmatory test for skin-related reactions to amoxicillin.
      Further studies are required to assess factors associated with the PC outcome
      groups.

PMID- 27043790
TI  - The Role of the Medical Physicist in Managing Radiation Dose and Communicating
      Risk in CT.
AB  - OBJECTIVE: This article discusses the discrepancy between the public's perception
      of radiation risk and the actual risks from low doses of ionizing radiation.
      Resources from the medical physics community that can be used to manage dose
      levels in CT examinations are reviewed. An approach is described for presenting
      information about radiation risks and benefits to patients that supports dose
      management and acknowledges that risks from the low doses of radiation used in
      medical imaging either are too low to be reliably detected or do not exist.
      CONCLUSION: When asked by a patient or a patient's family about the risk of
      radiation, it is incumbent on each of us to remember the tenet of justification
      first and foremost: If the examination is needed, the benefit will outweigh any
      small or potentially nonexistent risk. The next responsibility is to image the
      patient with care by adjusting the delivered dose to the patient size and to the
      diagnostic task.

PMID- 27043789
TI  - Comment on Publications from OpT2mise Study.

PMID- 27043791
TI  - Thermal stability of photoluminescence in Cu-doped Zn-In-S quantum dots for light
      emitting diodes.
AB  - The photoluminescence (PL) properties of the Cu:Zn-In-S core quantum dots (QDs)
      and core-shell QDs were systematically investigated by using steady-state and
      time-resolved PL spectra at temperatures ranging from 80 to 400 K. The effects of
      the shell structure and the host bandgap on the thermal stability of Cu dopant
      emissions were studied by measuring the change in the PL intensity and the
      lifetime. It was found that the PL intensities and lifetimes of the core and
      core/shell QDs with green, yellow, and red emissions almost decrease with
      increasing temperatures while their PL was quenched at 300 K and 400 K,
      respectively, indicating the shell-enhanced thermal stability of the PL. The
      emission wavelength of the QDs as a function of temperature was also provided.
      The mechanisms of Cu dopant emission and thermal quenching were discussed.
      Finally, the green, yellow, red, and white light emitting light emitting diodes
      (LEDs) were fabricated based on Cu:Zn-In-S QDs. 

PMID- 27043792
TI  - Luminescence Enhanced Eu(3+)/Gd(3+) Co-Doped Hydroxyapatite Nanocrystals as
      Imaging Agents In Vitro and In Vivo.
AB  - Biocompatible, biodegradable, and luminescent nano material can be used as an
      alternative bioimaging agent for early cancer diagnosis, which is crucial to
      achieve successful treatment. Hydroxyapatite (HAP) nanocyrstals have good
      biocompatibility and biodegradability, and can be used as an excellent host for
      luminescent rare earth elements. In this study, based on the energy transfer from
      Gd(3+) to Eu(3+), the luminescence enhanced imaging agent of Eu/Gd codoping HAP
      (HAP:Eu/Gd) nanocrystals are obtained via coprecipitation with plate-like shape
      and no change in crystal phase composition. The luminescence can be much elevated
      (up to about 120%) with a nonlinear increase versus Gd doping content, which is
      due to the energy transfer ((6)PJ of Gd(3+) -> (5)HJ of Eu(3+)) under 273 nm and
      the possible combination effect of the cooperative upconversion and the
      successive energy transfer under 394 nm, respectively. Results demonstrate that
      the biocompatible HAP:Eu/Gd nanocrystals can successfully perform cell labeling
      and in vivo imaging. The intracellular HAP:Eu/Gd nanocrystals display good
      biodegradability with a cumulative degradation of about 65% after 72 h. This
      biocompatible, biodegradable, and luminescence enhanced HAP:Eu/Gd nanocrystal has
      the potential to act as a fluorescent imaging agent in vitro and in vivo.

PMID- 27043795
TI  - Efficacy and Safety Assessment of Paclitaxel in Patients with Docetaxel-Resistant
      Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: Incomplete cross-resistances between paclitaxel (PTX) and docetaxel
      (DTX) has been demonstrated in several types of cancer. The objective of the
      present study was to assess the existence of cross-resistance between PTX and DTX
      in esophageal squamous cell carcinoma. METHODS: Patients in the PTX group
      received PTX without DTX pretreatment, patients in the prior DTX (Pr-DTX) group
      received PTX after the development of resistance to DTX, and patients in the DTX
      group received DTX without subsequent PTX treatment. RESULTS: A total of 73
      patients were enrolled. The response rates to PTX in the PTX and Pr-DTX groups
      were 22.7 and 20.0%, respectively. The median progression-free survival times
      from the first day of PTX treatment in the PTX and Pr-DTX groups were 113 (95% CI
      56-154) and 97 days (95% CI 36-189), respectively. The median overall survival
      times from the first day of DTX treatment in the Pr-DTX and DTX groups were 315
      (95% CI 124-453) and 148 days (95% CI 139-177), respectively. CONCLUSIONS: There
      is no or incomplete clinical cross-resistance between PTX and DTX in esophageal
      squamous cell carcinoma. Replacement of DTX with PTX is a suitable treatment
      option for patients with DTX-resistant esophageal squamous cell carcinoma.

PMID- 27043796
TI  - Priority for one's own stimulus in joint performance: evidence from an event
      related potential study.
AB  - To investigate priority of shared task representations (own vs. other) formed
      during joint task performance, event-related potentials were recorded while
      participants performed an auditory three-stimulus oddball task alone (individual
      condition) and with another participant (joint condition). Participants were
      required to discriminate between frequent standard tones and rare target tones,
      while ignoring nontargets assigned to a partner's action (i.e. no-go stimuli for
      one's own task performance). The parietal P3b was elicited for targets under both
      conditions. In contrast, P3b for nontargets was observed only in the joint
      condition, and in addition, it accompanied the frontal no-go P3. This implies
      that coactors share one another's task representations. Importantly, the
      emergence of P3b and no-go P3 for nontargets was delayed compared with P3b for
      targets, suggesting that shared task representations are serially applied to the
      stimulus processing and that one's own representations precede the other
      individual's representations.

PMID- 27043797
TI  - Health Care Communication Technology and Improved Access, Continuity, and
      Relationships: The Revolution Will Be Uberized.

PMID- 27043798
TI  - "I'm Dying, but I'm Not Dead Yet": Patient Decisions About Dying and Death.

PMID- 27043799
TI  - A Comprehensive Approach to the Patient at End of Life: Assessment of
      Multidimensional Suffering.
AB  - Pain is a multidimensional, complex experience. There are many challenges in
      identifying and meeting the needs of patients experiencing pain. Evaluation of
      pain from a bio-psycho-social-spiritual framework is particularly germane for
      patients approaching the end of life. This review explores the relation between
      the psychospiritual dimensions of suffering and the experience of physical pain,
      and how to assess and treat pain in a multidimensional framework. A review of
      empirical data on the relation between pain and suffering as well as
      interdisciplinary evidence-based approaches to alleviate suffering are provided. 

PMID- 27043800
TI  - Relation Between Physicians' Work Lives and Happiness.
AB  - OBJECTIVES: Although we know much about work-related physician burnout and the
      subsequent negative effects, we do not fully understand work-related physician
      wellness. Likewise, the relation of wellness and burnout to physician happiness
      is unclear. The purpose of this study was to examine how physician burnout and
      wellness contribute to happiness. METHODS: We sampled 2000 full-time physician
      members of the American Academy of Family Physicians. Respondents completed a
      demographics questionnaire, questions about workload, the Physician Wellness
      Inventory, the Maslach Burnout Inventory, and the Subjective Happiness Scale. We
      performed a hierarchical regression analysis with the burnout and wellness
      subscales as predictor variables and physician happiness as the outcome variable.
      RESULTS: Our response rate was 22%. Career purpose, personal accomplishment, and
      perception of workload manageability had significant positive correlations with
      physician happiness. Distress had a significant negative correlation with
      physician happiness. CONCLUSIONS: A sense of career meaning and accomplishment,
      along with a lack of distress, are important factors in determining physician
      happiness. The number of hours a physician works is not related to happiness, but
      the perceived ability to manage workload was significantly related to happiness.
      Wellness-promotion efforts could focus on assisting physicians with skills to
      manage the workload by eliminating unnecessary tasks or sharing workload among
      team members, improving feelings of work accomplishment, improving career
      satisfaction and meaning, and managing distress related to patient care.

PMID- 27043801
TI  - Survival of Trauma Victims Transported by Helicopter Who Required Cardiopulmonary
      Resuscitation Within the First Hour of Hospital Arrival.
AB  - OBJECTIVES: The purpose of the study was to review the impact on survival of
      trauma victims who were transported via helicopter ambulance versus ground
      transportation and who received cardiopulmonary resuscitation (CPR) within 1 hour
      of hospital arrival. METHODS: A retrospective analysis of the trauma patients who
      underwent CPR within 1 hour of arrival to the trauma centers and transported
      either via air or ground ambulances was performed. Data were extracted from the
      Research Data Set 2007-2010 from the American College of Surgeons National Trauma
      Data Bank. Patient and hospital characteristics were compared between the groups.
      Propensity score matching was performed to balance the baseline characteristics
      and absolute risk reduction was calculated using the McNemar test to evaluate the
      risk difference of survival at discharge with the mode of transportation.
      RESULTS: A total of 1269 patients qualified for the final analysis; 314 patients
      were transported by helicopter and 955 by ground ambulances. There were
      significant differences in baseline characteristics between the groups regarding
      age (P = 0.015), Injury Severity Score (P < 0.001), Glasgow Coma Scale (P <
      0.001), male sex (P < 0.001), race (P < 0.001), and injury type (blunt vs
      penetrating, P < 0.001). After propensity score matching, no significant
      differences were seen on baseline characteristics between the groups. The mean
      standardized difference was <10% between the groups after matching in all
      covariates. There was a higher rate of survival of patients who were brought in
      via helicopter ambulance (absolute risk reduction 0.066, confidence interval
      0.008-0.125, P = 0.02). CONCLUSIONS: Higher survival was seen in patients who
      were transported by helicopter ambulance and received CPR within 1 hour of
      hospital arrival.

PMID- 27043802
TI  - Commentary on "Survival of Trauma Victims Transported by Helicopter Who Required
      CPR Within the First Hour of Hospital Arrival".

PMID- 27043803
TI  - Longitudinal Trends in the Prevalence of Diabetes Mellitus in an Urban Emergency
      Department.
AB  - OBJECTIVE: The objective of this study was to examine the longitudinal trends in
      diabetes mellitus (DM) in emergency department (ED) patients and evaluate the
      factors associated with those trends. METHODS: We conducted a retrospective
      analysis of all patients who presented to the ED from 2006 to 2011. The presence
      of DM, height, and weight were recorded prospectively. The study was conducted in
      the ED of an urban, academic hospital with an average yearly volume of
      approximately 62,000 patients. Inclusion criteria were age 16 years and older;
      presentation to the ED for any reason; and documentation of height, weight, and
      history of DM. Data were analyzed in 1-year blocks, then examined for trends
      using linear regression analysis. Data also were examined by obesity class:
      normal (body mass index [BMI] 20-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)),
      obese (BMI 30-39.9 kg/m(2)), and extreme obesity (BMI >40 kg/m(2)). RESULTS:
      There was a statistically significant increase in the prevalence of type 2 DM
      during the study period. The percentage of type 2 DM for all patient visits
      increased progressively from 10.7% to 16.1% (r(2) 0.97). Progressive increases in
      yearly type 2 DM prevalence were observed for all BMI classes. The rate of change
      in the increase of DM was related directly to the degree of obesity. For the
      normal weight category, the percentage of patients with DM increased 0.5%/year
      (r(2) 0.92), overweight 0.7%/year (r(2) 0.88), obesity 1.0%/year (r(2) 0.90), and
      extreme obesity 1.4%/year (r(2) 0.94). Patient age increased slightly for all
      obesity groups, accounting for a 0.2% to 0.4%/year increase in the prevalence of
      DM in the population. CONCLUSIONS: In this longitudinal analysis, we found an
      increase in the prevalence of patients with DM and an increase in ED visits by
      patients with DM. Our results indicate that these increases are influenced most
      significantly by the obesity level of the patient.

PMID- 27043804
TI  - Commentary on "Longitudinal Trends in the Prevalence of Diabetes Mellitus in an
      Urban Emergency Department".

PMID- 27043805
TI  - Predictors of a Prolonged Length of Stay in Children with Perforated
      Appendicitis.
AB  - OBJECTIVES: Little is known about the factors that affect the length of stay
      (LOS) of children hospitalized for perforated appendicitis. The objective of this
      study was to identify clinical and demographic factors associated with a
      prolonged LOS (PLOS) in children with perforated appendicitis. METHODS: A
      retrospective cohort study was conducted using the records of 197 children 0 to
      17 years old with perforated appendicitis. The children were hospitalized at one
      of two teaching hospitals located in El Paso, Texas, and were discharged between
      January 2008 and January 2014. PLOS was defined as an LOS greater than the 75th
      percentile value in our patient cohort, which was 7 days. An initial log-binomial
      regression model failed to converge, and hence logistic regression was used to
      calculate adjusted incidence odds ratios (OR) for PLOS, 95% confidence intervals,
      P values, and a receiver operating characteristic curve. The best subset method
      was used to identify predictors for inclusion in the final model. RESULTS: The
      overall risk of PLOS was 23.4% (46/197). Approximately 76% of the children who
      experienced PLOS and 94% of those who did not have PLOS were Hispanic. After
      adjusting for insurance status, presence of an abscess, asthma, consulting
      interventional radiology, and various antibiotics, Hispanics were less likely
      than non-Hispanics to experience PLOS (adjusted OR 0.20; P = 0.003). Children
      whose providers consulted the interventional radiologist had an increased odds of
      PLOS (adjusted OR 3.64; P = 0.01). CONCLUSIONS: Hispanic ethnicity was associated
      with a lower odds of PLOS, whereas children who required the services of an
      interventional radiologist were more likely to experience PLOS.

PMID- 27043806
TI  - Fingernail Carriage of Methicillin-Resistant Staphylococcus aureus and Possible
      Correlation with Soft Tissue Infections in Children.
AB  - OBJECTIVES: Community-associated methicillin-resistant Staphylococcus aureus
      (MRSA) is a growing problem in the pediatric population, causing many soft tissue
      infections. This study was designed to examine fingernail carriage of MRSA in
      children and their caregivers as a possible link to community-associated MRSA
      soft tissue infections in children. METHODS: We documented the prevalence of MRSA
      under the fingernails of children and the caregivers of pediatric patients with
      soft tissue infections and compared the prevalence with MRSA under the
      fingernails of children and the caregivers of children with no history of soft
      tissue infections. Children with soft tissue infections and their caregivers (50
      subjects) had three fingernails of each hand swabbed and plated and these were
      compared with a control group of children and their caregivers (150 subjects) who
      had no history of MRSA or soft tissue infection. RESULTS: Caregivers and children
      in the study group were more likely than caregivers and the children in the
      control group to have MRSA under their fingernails (P < 0.05). Soft tissue
      infections in the study group were found most commonly in the diapering area
      (66%). CONCLUSIONS: MRSA carriage was evident under the fingernails of children
      and caregivers. Caregivers and their children who have soft tissue infections are
      more likely to have MRSA growth under fingernails than caregivers or their
      children who have no history of MRSA or soft tissue infections. Our study
      suggests that caregivers could be contributing to soft tissue infections in their
      children.

PMID- 27043807
TI  - Commentary on "Fingernail Carriage of Methicillin-Resistant Staphylococcus aureus
      and Possible Correlation with Soft Tissue Infections in Children".

PMID- 27043808
TI  - PROMISE of Coronary CT Angiography: Precise and Accurate Diagnosis and Prognosis
      in Coronary Artery Disease.
AB  - Coronary computed tomography angiography (CCTA) is a rapidly growing and powerful
      diagnostic test that offers a great deal of precision with respect to diagnosing
      coronary artery disease (CAD). Guideline statements for patients with stable
      ischemic heart disease have recommended CCTA for only a limited portion of
      intermediate-risk patients who have relative or absolute contraindications for
      exercise or vasodilator stress testing. The publication of two large, prospective
      randomized clinical trials, the Prospective Multicenter Imaging Study for
      Evaluation of Chest Pain and the Scottish Computed Tomography of the Heart Trial
      are likely to expand these indications. These new data from large trials, in
      addition to other studies, show that CCTA is highly sensitive for the detection
      of CAD, identifies high-risk patients for cardiac events based on extent or
      plaque morphology of CAD that would not be identified by other noninvasive means,
      and provides significantly greater diagnostic certainty for proper treatment,
      including referral for invasive coronary angiography with revascularization more
      appropriately. Superior diagnostic accuracy and prognostic data with CCTA, when
      compared with other functional stress tests, may result in a reduction in
      unnecessary downstream testing and cost savings. In addition, newer CCTA
      applications hold the promise of providing a complete evaluation of a patient's
      coronary anatomy as well as a per-vessel ischemic evaluation. This review focuses
      on the interval knowledge obtained from newer data on CCTA in patients with
      stable ischemic heart disease, primarily focusing on the contributions of the
      Prospective Multicenter Imaging Study for Evaluation of Chest Pain and the
      Scottish Computed Tomography of the Heart Trial. 

PMID- 27043809
TI  - A Clinician's Guide to Fecal Occult Blood Testing for Colorectal Cancer.
AB  - Colorectal cancer (CRC) is a significant healthcare issue, with substantial
      morbidity and mortality. Screening for CRC is essential in the prevention and
      treatment of this disease. The two most common CRC screening modalities are
      colonoscopy and the stool-based occult blood test, with two types of stool-based
      occult blood tests: the guaiac-based fecal occult blood test (FOBT) and the
      immunochemical FOBT. Despite many similarities, these two stool tests are
      different and often are confused in clinical practice. In an effort to improve
      awareness of these testing modalities, this review provides extensive information
      on both of these FOBTs, as well as discusses comparisons in the literature
      between these stool-based blood tests and other screening modalities such as
      stool DNA and colonoscopy. 

PMID- 27043810
TI  - Commentary on "A Clinician's Guide to Fecal Occult Blood Testing for Colorectal
      Cancer".

PMID- 27043811
TI  - Perceptions of Older Adults, Hematologists, and Medical Oncologists in Cancer
      Care.
AB  - OBJECTIVES: The purpose of this study was to assess and compare the perceptions
      of hematologists, medical oncologists, cancer patients aged 65 years and older,
      and family members/caregivers regarding the value of a geriatric assessment (GA)
      in the management of older adults with cancer. METHODS: Participants included
      adults with cancer aged 65 years and older (n = 66), patient family
      members/caregivers (n = 32), and physicians (n = 42). A patient survey, a
      caregiver/family survey, and an online physician survey targeted to hematologists
      and medical oncologists were distributed at a large cancer center in a major
      academic health system in the New York metropolitan area. The chi(2) test or the
      Fisher exact test was used to compare the cohorts for responses to geriatric
      domains in a GA. RESULTS: Comparisons for each of the 17 GA domains between
      patient and family member and caregiver responses showed concordance, except for
      the perception of comorbidities; 16.7% of patients indicated that comorbidities
      were an issue, compared with 29.0% of family/caregivers (P = 0.047). Physicians
      indicated that a GA would be most helpful in addressing cognitive impairment
      (91.4%), falls (91.4%), and functional status (88.6%). CONCLUSIONS: A GA would be
      useful for physicians and older adults with cancer. Hematologists and medical
      oncologists recognize the utility of a GA and are receptive to a
      multidisciplinary geriatrics-oncology collaboration.

PMID- 27043812
TI  - Commentary on "Perceptions of Older Adults, Hematologists, and Medical
      Oncologists in Cancer Care".

PMID- 27043813
TI  - Survey of Provider Transfusion Practices for Oncology Patients in an Academic
      Medical Center.
AB  - OBJECTIVES: Hospitalized oncology patients receive care from a variety of
      professionals, each of whom plays a role in decisions related to blood
      transfusions. We sought to examine differences in transfusion practices based on
      professional role, years of experience, and patient clinical scenario. METHODS:
      We surveyed general medicine residents, hospitalists, and oncologists caring for
      inpatients at a large academic medical center between August 2013 and June 2014.
      Respondents reported transfusion practices in three different patient scenarios:
      a generally healthy patient, a patient with solid tumor malignancy, and a patient
      with hematologic malignancy. We also assessed rationale for transfusion
      practices. Bivariate comparisons of respondent characteristics and transfusion
      threshold were conducted using the Fisher exact test. Multivariate logistic
      regression was performed to assess the relative relations among professional
      role, years in practice, clinical scenario, and transfusion threshold <7 g/dL.
      RESULTS: Of 158 physicians surveyed, 97 responded (61.4%). In bivariate analyses,
      fewer oncologists than residents or hospitalists used a threshold of <7 g/dL, but
      the result was significant for only one of three scenarios. The multivariate odds
      of transfusing at a threshold <7 g/dL were significantly higher among
      nononcologists (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.03-4.28).
      Residents and practitioners in practice for <4 years also were more likely to use
      a threshold <7 g/dL (OR 1.82, 95% CI 0.99-3.33). Providers were less likely to
      use a restrictive threshold when an underlying malignancy was present (solid
      tumor OR 0.31, 95% CI 0.15-0.64; hematologic malignancy OR 0.34, 95% CI 0.16
      0.70). CONCLUSIONS: Transfusion thresholds differed based on professional role,
      years in practice, and patient scenario. Further research is needed to determine
      the optimal transfusion threshold for oncology patients.

PMID- 27043814
TI  - A Systematic Evaluation of Factors Contributing to Overdiagnosis and
      Overtreatment.

PMID- 27043815
TI  - Mechanistic studies on intramolecular C-H trifluoromethoxylation of
      (hetero)arenes via OCF3-migration.
AB  - The one-pot two-step intramolecular aryl and heteroaryl C-H
      trifluoromethoxylation recently reported by our group has provided a general,
      scalable, and operationally simple approach to access a wide range of
      unprecedented and valuable OCF3-containing building blocks. Herein we describe
      our investigations to elucidate its reaction mechanism. Experimental data
      indicate that the O-trifluoromethylation of N-(hetero)aryl-N-hydroxylamine
      derivatives is a radical process, whereas the OCF3-migration step proceeds via a
      heterolytic cleavage of the N-OCF3 bond followed by rapid recombination of a
      short-lived ion pair. Computational studies further support the proposed ion pair
      reaction pathway for the OCF3-migration process. We hope that the current study
      would provide useful insights for the development of new transformations using
      versatile N-(hetero)aryl-N-hydroxylamine synthons. 

PMID- 27043817
TI  - Exploiting a Difference in Leaving Group Ability: An Approach to beta-Substituted
      Monofluoroalkenes Using gem-Chlorofluoropropenes.
AB  - The superior nucleofuge character of chlorine over fluorine was taken advantage
      of in the selective SN2' substitution reaction of gem-chlorofluoropropenes,
      allowing for the clean formation of beta-substituted monofluoroalkenes under
      metal-free conditions. Numerous N-, S-, O-, and C-nucleophiles behaved nicely in
      this system. Further synthetic transformations of selected monofluoroalkenes were
      also accomplished. 

PMID- 27043816
TI  - Emergent properties of neural repair: elemental biology to therapeutic concepts.
AB  - Stroke is the leading cause of adult disability. The past decade has seen
      advances in basic science research of neural repair in stroke. The brain forms
      new connections after stroke, which have a causal role in recovery of function.
      Brain progenitors, including neuronal and glial progenitors, respond to stroke
      and initiate a partial formation of new neurons and glial cells. The molecular
      systems that underlie axonal sprouting, neurogenesis, and gliogenesis after
      stroke have recently been identified. Importantly, tractable drug targets exist
      within these molecular systems that might stimulate tissue repair. These basic
      science advances have taken the field to its first scientific milestone; the
      elemental principles of neural repair in stroke have been identified. The next
      stages in this field involve understanding how these elemental principles of
      recovery interact in the dynamic cellular systems of the repairing brain.
      Emergent principles arise out of the interaction of the fundamental or elemental
      principles in a system. In neural repair, the elemental principles of brain
      reorganization after stroke interact to generate higher order and distinct
      concepts of regenerative brain niches in cellular repair, neuronal networks in
      synaptic plasticity, and the distinction of molecular systems of
      neuroregeneration. Many of these emergent principles directly guide the
      development of new therapies, such as the necessity for spatial and temporal
      control in neural repair therapy delivery and the overlap of cancer and neural
      repair mechanisms. This review discusses the emergent principles of neural repair
      in stroke as they relate to scientific and therapeutic concepts in this field.
      Ann Neurol 2016;79:895-906.

PMID- 27043818
TI  - Correction to "Comprehensive Cross-Linking Mass Spectrometry Reveals Parallel
      Orientation and Flexible Conformations of Plant HOP2-MND1".

PMID- 27043819
TI  - A Performance Analysis of Public Expenditure on Maternal Health in Mexico.
AB  - We explore the relationship between public expenditure, coverage of adequate ANC
      (including timing, frequent and content), and the maternal mortality ratio-
      adjusted by coverage of adequate ANC--observed in Mexico in 2012 at the State
      level. Additionally, we examine the inequalities and concentration of public
      expenditure between populations with and without Social Security. Results suggest
      that in the 2003-2011 period, the public expenditure gap between women with and
      without Social Security decreased 74%, however, the distribution is less
      equitable among women without Social Security, across the States. Despite high
      levels of coverage on each dimension of ANC explored, coverage of adequate ANC
      was lower among Social Security than non-Social Security women. This variability
      results in differences up to 1.5 times in State-adjusted maternal mortality rate
      at the same level of expense and maternal mortality rate, respectively. The
      increase in the economic resources is only a necessary condition for achieving
      improved health outcomes. Providing adequate health services and achieving
      efficient, effective and transparent use of resources in health, are critical
      elements for health systems performance. The attainment of universal effective
      coverage of maternal health and reducing maternal mortality in Mexico, requires
      the adjustment of policy innovations including the rules of allocation and
      execution of health resources. Health policies should be designed on a more
      holistic view promoting a balance between accessibility, effective implementation
      and rigorous stewardship.

PMID- 27043820
TI  - Selective Reduction of CO2 to CH4 by Tandem Hydrosilylation with Mixed Al/B
      Catalysts.
AB  - This contribution reports the first example of highly selective reduction of CO2
      into CH4 via tandem hydrosilylation with mixed main-group organo-Lewis acid (LA)
      catalysts [Al(C6F5)3 + B(C6F5)3] {[Al] + [B]}. As shown by this comprehensive
      experimental and computational study, in this unique tandem catalytic process,
      [Al] effectively mediates the first step of the overall reduction cycle, namely
      the fixation of CO2 into HCOOSiEt3 (1) via the LA-mediated C?O activation, while
      [B] is incapable of promoting the same transformation. On the other hand, [B] is
      shown to be an excellent catalyst for the subsequent reduction steps 2-4, namely
      the hydrosilylation of the more basic intermediates [1 to H2C(OSiEt3)2 (2) to
      H3COSiEt3 (3) and finally to CH4] through the frustrated Lewis pair (FLP)-type Si
      H activation. Hence, with the required combination of [Al] and [B], a highly
      selective hydrosilylative reduction of CO2 system has been developed, achieving
      high CH4 production yield up to 94%. The remarkably different catalytic behaviors
      between [Al] and [B] are attributed to the higher overall Lewis acidity of [Al]
      derived from two conflicting factors (electronic and steric effects), which
      renders the higher tendency of [Al] to form stable [Al]-substrate (intermediate)
      adducts with CO2 as well as subsequent intermediates 1, 2, and 3. Overall, the
      roles of [Al] and [B] are not only complementary but also synergistic in the
      total reduction of CO2, which render both [Al]-mediated first reduction step and
      [B]-mediated subsequent steps catalytic.

PMID- 27043821
TI  - Inactivation of Semicarbazide-Sensitive Amine Oxidase Stabilizes the Established
      Atherosclerotic Lesions via Inducing the Phenotypic Switch of Smooth Muscle
      Cells.
AB  - Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO)
      activity is associated with the severity of carotid atherosclerosis in clinic,
      the current study aims to investigate whether SSAO inactivation by semicarbazide
      is beneficial for established atherosclerotic lesions in LDLr knockout mice on a
      high-fat/high- cholesterol Western-type diet or after dietary lipid lowering.
      Despite no impact on plasma total cholesterol levels, the infiltration of
      circulating monocytes into peripheral tissues, and the size of atherosclerotic
      lesions, abrogation of SSAO activity resulted in the stabilization of established
      lesions as evidenced by the increased collagen contents under both conditions.
      Moreover, SSAO inactivation decreased Ly6Chigh monocytosis and lesion macrophage
      contents in hypercholesterolemic mice, while no effect was observed in mice after
      normalization of hypercholesterolemia by dietary lipid lowering. Strikingly,
      abrogation of SSAO activity significantly increased not only the absolute numbers
      of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic
      phenotype in established lesions of mice regardless of plasma cholesterol levels.
      Overall, our data indicate that SSAO inactivation in vivo stabilizes the
      established plaques mainly via inducing the switch of SMCs from a contractile to
      a synthetic phenotype. Targeting SSAO activity thus may represent a potential
      treatment for patients with atherosclerosis. 

PMID- 27043822
TI  - Shaking B Mediates Synaptic Coupling between Auditory Sensory Neurons and the
      Giant Fiber of Drosophila melanogaster.
AB  - The Johnston's Organ neurons (JONs) form chemical and electrical synapses onto
      the giant fiber neuron (GF), as part of the neuronal circuit that mediates the GF
      escape response in Drosophila melanogaster. The purpose of this study was to
      identify which of the 8 Drosophila innexins (invertebrate gap junction proteins)
      mediates the electrical connection at this synapse. The GF is known to express
      Shaking B (ShakB), specifically the ShakB(N+16) isoform only, at its output
      synapses in the thorax. The shakB2 mutation disrupts these GF outputs and also
      abolishes JON-GF synaptic transmission. However, the identity of the innexin that
      forms the presynaptic hemichannels in the JONs remains unknown. We used
      electrophysiology, immunocytochemistry and dye injection, along with
      presynaptically-driven RNA interference, to investigate this question. The
      amplitude of the compound action potential recorded in response to sound from the
      base of the antenna (sound-evoked potential, or SEP) was reduced by RNAi of the
      innexins Ogre, Inx3, Inx6 and, to a lesser extent Inx2, suggesting that they
      could be required in JONs for proper development, excitability, or
      synchronization of action potentials. The strength of the JON-GF connection
      itself was reduced to background levels only by RNAi of shakB, not of the other
      seven innexins. ShakB knockdown prevented Neurobiotin coupling between GF and
      JONs and removed the plaques of ShakB protein immunoreactivity that are present
      at the region of contact. Specific shakB RNAi lines that are predicted to target
      the ShakB(L) or ShakB(N) isoforms alone did not reduce the synaptic strength,
      implying that it is ShakB(N+16) that is required in the presynaptic neurons.
      Overexpression of ShakB(N+16) in JONs caused the formation of ectopic dye
      coupling, whereas ShakB(N) prevented it altogether, supporting this conclusion
      and also suggesting that gap junction proteins may have an instructive role in
      synaptic target choice. 

PMID- 27043823
TI  - Controlling Harmful Cyanobacteria: Taxa-Specific Responses of Cyanobacteria to
      Grazing by Large-Bodied Daphnia in a Biomanipulation Scenario.
AB  - Lake restoration practices based on reducing fish predation and promoting the
      dominance of large-bodied Daphnia grazers (i.e., biomanipulation) have been the
      focus of much debate due to inconsistent success in suppressing harmful
      cyanobacterial blooms. While most studies have explored effects of large-bodied
      Daphnia on cyanobacterial growth at the community level and/or on few dominant
      species, predictions of such restoration practices demand further understanding
      on taxa-specific responses in diverse cyanobacterial communities. In order to
      address these questions, we conducted three grazing experiments during summer in
      a eutrophic lake where the natural phytoplankton community was exposed to an
      increasing gradient in biomass of the large-bodied Daphnia magna. This allowed
      evaluating taxa-specific responses of cyanobacteria to Daphnia grazing throughout
      the growing season in a desired biomanipulation scenario with limited fish
      predation. Total cyanobacterial and phytoplankton biomasses responded negatively
      to Daphnia grazing both in early and late summer, regardless of different
      cyanobacterial densities. Large-bodied Daphnia were capable of suppressing the
      abundance of Aphanizomenon, Dolichospermum, Microcystis and Planktothrix bloom
      forming cyanobacteria. However, the growth of the filamentous Dolichospermum
      crassum was positively affected by grazing during a period when this
      cyanobacterium dominated the community. The eutrophic lake was subjected to
      biomanipulation since 2005 and nineteen years of lake monitoring data (1996-2014)
      revealed that reducing fish predation increased the mean abundance (50%) and body
      size (20%) of Daphnia, as well as suppressed the total amount of nutrients and
      the growth of the dominant cyanobacterial taxa, Microcystis and Planktothrix.
      Altogether our results suggest that lake restoration practices solely based on
      grazer control by large-bodied Daphnia can be effective, but may not be
      sufficient to control the overgrowth of all cyanobacterial diversity. Although
      controlling harmful cyanobacterial blooms should preferably include other
      measures, such as nutrient reductions, our experimental assessment of taxa
      specific cyanobacterial responses to large-bodied Daphnia and long-term
      monitoring data highlights the potential of such biomanipulations to enhance the
      ecological and societal value of eutrophic water bodies. 

PMID- 27043824
TI  - Evaluating p97 Inhibitor Analogues for Potency against p97-p37 and p97-Npl4-Ufd1
      Complexes.
AB  - We previously found that the p97 cofactor, p47, significantly decreased the
      potency of some ATP-competitive p97 inhibitors such as ML240 [2-(2-amino-1H
      benzo[d]imidazol-1-yl)-N-benzyl-8-methoxyquinazolin-4-amine] and ML241 [2-(2H
      benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8 tetrahydroquinazolin-4-amine]. In
      this study, we aimed to evaluate inhibitor potencies against two additional p97
      cofactor complexes, p97-p37 and p97-Npl4-Ufd1. We focused on these two cofactor
      complexes, because the protein sequence of p37 is 50 % identical to that of p47,
      and the Npl4-Ufd1 heterodimer (NU) is the most-studied p97 cofactor complex. We
      screened 200 p97 inhibitor analogues for their ability to inhibit the ATPase
      activity of p97 alone and of p97-p37 and p97-NU complexes. In contrast to the
      effect of p47, p37 and NU did not significantly change the potencies of most of
      the compounds. These results highlight differences among p97 cofactors in
      influencing p97 conformation and effects of inhibitors on p97 complexes, as
      compared to p97 alone. Continued efforts are needed to advance the development of
      complex-specific p97 inhibitors.

PMID- 27043825
TI  - CPAD, Curated Protein Aggregation Database: A Repository of Manually Curated
      Experimental Data on Protein and Peptide Aggregation.
AB  - Accurate distinction between peptide sequences that can form amyloid-fibrils or
      amorphous beta-aggregates, identification of potential aggregation prone regions
      in proteins, and prediction of change in aggregation rate of a protein upon
      mutation(s) are critical to research on protein misfolding diseases, such as
      Alzheimer's and Parkinson's, as well as biotechnological production of protein
      based therapeutics. We have developed a Curated Protein Aggregation Database
      (CPAD), which has collected results from experimental studies performed by
      scientific community aimed at understanding protein/peptide aggregation. CPAD
      contains more than 2300 experimentally observed aggregation rates upon mutations
      in known amyloidogenic proteins. Each entry includes numerical values for the
      following parameters: change in rate of aggregation as measured by fluorescence
      intensity or turbidity, name and source of the protein, Uniprot and Protein Data
      Bank codes, single point as well as multiple mutations, and literature citation.
      The data in CPAD has been supplemented with five different types of additional
      information: (i) Amyloid fibril forming hexa-peptides, (ii) Amorphous beta
      aggregating hexa-peptides, (iii) Amyloid fibril forming peptides of different
      lengths, (iv) Amyloid fibril forming hexa-peptides whose crystal structures are
      available in the Protein Data Bank (PDB) and (v) Experimentally validated
      aggregation prone regions found in amyloidogenic proteins. Furthermore, CPAD is
      linked to other related databases and resources, such as Uniprot, Protein Data
      Bank, PUBMED, GAP, TANGO, WALTZ etc. We have set up a web interface with
      different search and display options so that users have the ability to get the
      data in multiple ways. CPAD is freely available at
      http://www.iitm.ac.in/bioinfo/CPAD/. The potential applications of CPAD have also
      been discussed. 

PMID- 27043827
TI  - Insight into the epidemiology of cutaneous squamous cell carcinoma with
      perineural spread.
AB  - BACKGROUND: Perineural spread (PNS) of cutaneous squamous cell carcinoma of the
      head and neck (SCCHN) can be associated with poor outcomes. Disease understanding
      and awareness is limited leading to delayed diagnosis and treatment. The purpose
      of this study was to identify epidemiological features of patients with PNS of
      cutaneous SCCHN. METHODS: Tumor characteristics and demographics of patients with
      PNS of cutaneous SCCHN managed through a single institution were collected
      between 1998 and 2013. RESULTS: One hundred twenty patients were included in this
      study. The majority had a history of skin cancer (85.8%). The median time from
      primary tumor treatment to PNS symptom onset was 16 months (range, 1-86 months).
      A total of 34.2% had no perineural invasion (PNI) detected in the primary, and
      22.5% had no known primary tumor. Only 5.8% of the patients had nodal involvement
      at presentation. CONCLUSION: Patients can present with PNS from cutaneous SCCHN
      with no known primary tumor or with primary tumors without PNI. The majority of
      patients presented without regional nodal involvement. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 38: 1416-1420, 2016.

PMID- 27043826
TI  - 2014 French guidelines for hepatitis B and C screening: a combined targeted and
      mass testing strategy of chronic viruses namely HBV, HCV and HIV.
AB  - BACKGROUND & AIMS: Worldwide and, to a lesser extent, in France, a minority of
      individuals infected with hepatitis B (HBV) and C (HCV) is aware of its status.
      Given the current availability of highly effective anti-HBV and anti-HCV agents,
      the high rate of undiagnosed people, associated with individual and community
      prejudices (liver disease worsening, persistence of a hidden transmission
      reservoir and medicoeconomic burden of delayed care), is unacceptable. METHODS:
      On the occasion of the first French general report on viral hepatitis, new
      recommendations for HBV and HCV testing were issued. We aim to introduce the new
      French strategy for HBV and HCV screening, and to describe the underlying
      epidemiological data. RESULTS: These recommendations comprise various items.
      First, the screening of chronic viruses, namely HBV, HCV and HIV, should be quasi
      systematically combined. Second, the targeted screening of groups at risk of
      viral exposure must be strengthened. Third, routine testing for each of these
      three viruses should be offered at least once to men of 18-60 years old who had
      never been tested. In parallel, in pregnant women, in addition to HIV-HBV
      screening, currently recommended HCV testing should be routinely performed during
      the first trimester of pregnancy. In order to best achieve the target
      populations, community initiatives that propose testing actions should be
      encouraged, particularly those including rapid point-of-care tests. CONCLUSIONS:
      Overall, these recommendations aim to define a comprehensive testing strategy for
      chronic viral infections, emphasizing both targeted screening and mass screening
      and considering jointly HBV, HCV and HIV.

PMID- 27043828
TI  - Functional Alterations in Order Short-Term Memory Networks in Adults With
      Dyslexia.
AB  - Dyslexia is characterized not only by reading impairment but also by short-term
      memory (STM) deficits, and this particularly for the retention of serial order
      information. Here, we explored the functional neural correlates associated with
      serial order STM performance of adults with dyslexia for verbal and visual STM
      tasks. Relative to a group of age-matched controls, the dyslexic group showed
      abnormal activation in a network associated with order STM encompassing the right
      intraparietal and superior frontal sulcus, and this for both verbal and visual
      order STM conditions. This study highlights long-lasting alterations in non
      language neural substrates and processes in dyslexia. 

PMID- 27043829
TI  - Frontotemporal Coherence and Executive Functions Contribute to Episodic Memory
      During Middle Childhood.
AB  - Contributions of differential behavioral (executive functions) and
      electrophysiological (frontal-temporal electroencephalogram or EEG coherence)
      measures to episodic memory performance were examined during middle childhood.
      Cognitive flexibility and right frontotemporal functional connectivity during
      encoding (F4/T8), as well as left frontotemporal functional connectivity during
      retrieval (Fp1/T7), contributed to episodic memory performance in a sample of 9
      12-year-olds. These results suggest that executive functions differentially
      influence episodic memory, as does left and right frontotemporal functional
      connectivity during different portions of the memory task. 

PMID- 27043831
TI  - Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk:
      Significant Proteolysis in Lactation.
AB  - Significant proteolysis may occur during milk synthesis and secretion, as
      evidenced by the presence of protease-protease inhibitor complex containing the
      activated form of the type 2 transmembrane serine protease matriptase and the
      transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify
      other proteolysis events that may occur during lactation, human milk was analyzed
      for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In
      addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also
      detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored
      serine protease. HAI-2 was also detected in complexes, the majority of which
      appear to be part of higher-order complexes, which do not bind to ionic exchange
      columns or immunoaffinity columns, suggesting that HAI-2 and its target proteases
      may be incorporated into special protein structures during lactation. The small
      proportion HAI-2 species that could be purified contain matriptase or prostasin.
      Human mammary epithelial cells are the likely cellular sources for these HAI-1
      and HAI-2 complexes with matriptase and prostasin given that these protease
      inhibitor complexes with the exception of prostasin-HAI-2 complex were detected
      in milk-derived mammary epithelial cells. The presence of these protease
      inhibitor complexes in human milk provides in vivo evidence that the proteolytic
      activity of matriptase and prostasin are significantly elevated at least during
      lactation, and possibly contribute to the process of lactation, and that they are
      under tight control by HAI-1 and HAI-2. 

PMID- 27043832
TI  - Sclerosing Polycystic Adenosis: A Rare Tumor of the Salivary Glands.
AB  - CASE PRESENTATION: A 74-year-old woman presented to the Head and Neck Surgery
      clinic with a 4-year history of a slowly growing, painful, left-sided neck mass
      in the tail of the parotid gland. Fine-needle aspiration suggested well
      differentiated adenocarcinoma. DISCUSSION AND RESULTS: The patient underwent a
      superficial parotidectomy and super-selective neck dissection (level 2).
      Pathology revealed a tumor consistent with sclerosing polycystic adenosis.
      CONCLUSION: Sclerosing polycystic adenosis is a rare inflammatory process that
      causes fibrocystic changes in the salivary gland. Apocrine-like metaplasia and
      epithelial atypia are common pathologic features. To our knowledge, a total of 51
      cases have been described in the English-language literature.

PMID- 27043833
TI  - Emergency Care of Patients with Acute Ischemic Stroke in the Kaiser Permanente
      Southern California Integrated Health System.
AB  - CONTEXT: Tissue plasminogen activator (tPA) is underutilized for treatment of
      acute ischemic stroke. OBJECTIVE: To determine whether the probability of tPA
      administration for patients with ischemic stroke in an integrated health care
      system improved from 2009 to 2013, and to identify predictors of tPA
      administration. DESIGN: Retrospective analysis of all ischemic stroke
      presentations to 14 Emergency Departments between 2009 and 2013. A generalized
      linear mixed-effects model identified patient and hospital predictors of tPA.
      MAIN OUTCOME MEASURES: Primary outcome was tPA administration; secondary outcomes
      were door-to-imaging and door-to-needle times and tPA-related bleeding
      complications. RESULTS: Of the 11,630 patients, 3.9% received tPA. The likelihood
      of tPA administration increased with presentation in 2012 and 2013 (odds ratio
      [OR] = 1.75; 95% confidence interval [CI] = 1.26-2.43; and OR = 2.58; 95% CI =
      1.90-3.51), female sex (OR = 1.27; 95% CI = 1.04-1.54), and ambulance arrival (OR
      = 2.17; 95% CI = 1.76-2.67), and decreased with prior stroke (OR = 0.47; 95% CI =
      0.25-0.89) and increased age (OR = 0.98; 95% CI = 0.97-0.99). Likelihood varied
      by Medical Center (pseudo-intraclass correlation coefficient 13.5%). Among tPA
      treated patients, median door-to-imaging time was 15 minutes (interquartile
      range, 9-23 minutes), and door-to-needle time was 73 minutes (interquartile
      range, 55-103 minutes). The rate of intracranial hemorrhage was 4.2% and 0.9%
      among tPA- and non-tPA treated patients (p < 0.001). CONCLUSION: Acute ischemic
      stroke care improved over time in this integrated health system. Better
      understanding of differences in hospital performance will have important quality
      improvement and policy implications.

PMID- 27043834
TI  - Wilms Tumor: An Uncommon Entity in the Adult Patient.
AB  - Wilms tumor, the most common kidney tumor in children, is rarely seen in adults,
      making it a challenge for the adult oncologist to diagnose and treat. Unlike with
      renal cell carcinoma, patients with Wilms tumor should receive adjuvant
      chemotherapy with or without radiation therapy. Adult oncologists may not be
      familiar with pediatric oncology protocols, so it is important to consult with
      pediatric oncologists who have more experience in this disease. Multimodal
      therapy based on pediatric protocols improved the outcomes of adults with Wilms
      tumor worldwide. We report a rare case of a 24-year-old woman with a slow-growing
      mass of the left kidney during a 4-year period. The mass was surgically removed
      and final diagnosis confirmed by pathology to be Wilms tumor. The patient
      received adjuvant chemotherapy and has been free of disease since 2014.

PMID- 27043835
TI  - Onset of Ulcerative Colitis after Helicobacter pylori Eradication Therapy: A Case
      Report.
AB  - In Japan, Helicobacter pylori eradication has been approved since 2013 for
      treatment of H pylori-induced chronic gastritis, in an attempt to reduce the
      prevalence of gastric cancer, a leading cancer in Japan. H pylori infection
      affects more than 50% of the world's population. H pylori eradication therapy is
      generally safe. To our knowledge, no case of newly diagnosed ulcerative colitis
      occurring immediately after H pylori eradication therapy has previously been
      reported.A 63-year-old man received a diagnosis of chronic gastritis and H pylori
      infection. In early March 2014, primary H pylori eradication therapy was
      initiated; lansoprazole, amoxicillin, and clarithromycin were administered for 1
      week. Beginning on the fourth day, he had watery diarrhea twice a day. From the
      11th day, bloody stools and watery diarrhea increased to 6 times a day.
      Colonoscopy, performed on the 40th day after termination of drug therapy,
      revealed diffuse inflammation in the distal aspect of the colon, with histologic
      findings consistent with ulcerative colitis. He was admitted to the hospital and
      was provided with a semivegetarian diet and metronidazole. He noticed a gradual
      decrease in the amount of blood in his feces then a disappearance of the blood. A
      fecal occult blood test on the 11th hospital day recorded 337 ng/mL. Fecal occult
      blood test is not indicated during macroscopic bloody stool but is indicated
      after disappearance of bloody stool. Therefore, he achieved clinical remission by
      the 11th hospital day. He was in remission on discharge.New onset of ulcerative
      colitis should be added to a list of adverse events of H pylori eradication
      therapy.

PMID- 27043836
TI  - Sexual Health Research With Young Black Men Who Have Sex With Men: Experiences of
      Benefits and Harms.
AB  - Young Black men who have sex with men (YBMSM) are often underrepresented in
      sexual health research because of concerns about safety, privacy, and the
      potential for research harms. Empirical data are needed to understand YBMSM
      experience of participating in research, benefits and harms (discomfort), to
      inform policy and regulatory decisions. Using qualitative methods, this article
      examines 50 YBMSM, aged 15-19 years, experiences of benefits/harms, challenges of
      participating in sexual health research, and contextual factors impacting
      research experiences. Participants were asked about benefits and harms
      experienced in answering questions about sexual orientation, first same-sex
      attraction, and same-sex sexual experiences after completing an in-depth
      interview. Interviews were transcribed and coded. Inductive open coding was used
      to identify themes within and between interviews. Participants were able to
      describe perceived direct benefits resulting from research interview
      participation, including awareness of risky sexual behaviors, a safe space to
      share early coming out stories and same-sex sexual experiences, and a sense of
      empowerment and comfort with one's sexual orientation. Indirect benefits
      described by participants included perceptions of helping others and the larger
      gay community. Few participants described harms (discomfort recalling
      experiences). Our data suggest that participating in qualitative sexual health
      research focused on sexual orientation, sexual attraction, and early same-sex
      sexual experiences may result in minimal harms for YBMSM and multiple benefits,
      including feeling more comfortable than in a general medical visit.

PMID- 27043837
TI  - Characteristics of Men Who Have Sex With Men Who Use Smartphone Geosocial
      Networking Applications and Implications for HIV Interventions: A Systematic
      Review and Meta-Analysis.
AB  - Men who have sex with men (MSM) are increasingly using geosocial networking (GSN)
      mobile applications (apps) designed for MSM to socialize and seek sex partners.
      We systematically reviewed studies on the characteristics of app-using MSM and
      the potential feasibility of app-based HIV interventions. Existing studies
      provided limited parameters to compare characteristics and sexual behaviors
      between app-using and non-app-using MSM. Available data showed that: compared to
      non-app-using MSM, app-using MSM tended to be younger, identified as White (in
      the US and Australia), have higher educational level, report higher incomes, and
      had a higher rate of engagement in risky sexual behaviors and STIs. Compared to
      non-app-using MSM, app-using MSM were more likely to have tested for HIV in
      lifetime (Pooled odds ratio = 2.1, 95 % confidence interval: 1.7-2.6) and have
      similar HIV prevalence. Up to 676 MSM were recruited in 1 day via apps. In the
      current literature, there was a lack of (1) comparable parameters to measure
      sexual risk; (2) large longitudinal studies to clarify behavioral changes and
      HIV/STI incidence over time, comparing app-using and non-app-using MSM; (3)
      studies to examine the feasibility and efficacy of using apps to promote HIV
      testing among MSM; and (4) studies on similar topics from countries other than
      the US, Australia, and China. MSM GSN apps should be utilized in future HIV
      prevention and control endeavors. Researchers and health providers should
      collaborate with GSN app developers on these endeavors.

PMID- 27043838
TI  - Cobalt-Carbon Core-Shell Nanoparticles Aligned on Wrinkle of N-Doped Carbon
      Nanosheets with Pt-Like Activity for Oxygen Reduction.
AB  - A one-step soft-template induced strategy is demonstrated for the controlled
      synthesis of nitrogen-enriched core-shell structured cobalt-carbon nanoparticles
      (NPs) sequentially aligned on wrinkles of N-doped carbon nanosheets (Co-C@NWCs).
      The key feature of Co-C@NWCs for ORR catalysis enhancement is that it combines
      high catalytic centers of Co-C core-shell NPs with the wrinkle of carbon
      nanosheets with high electron donation ability. 

PMID- 27043839
TI  - Powdery mildew suppresses herbivore-induced plant volatiles and interferes with
      parasitoid attraction in Brassica rapa.
AB  - The co-occurrence of different antagonists on a plant can greatly affect
      infochemicals with ecological consequences for higher trophic levels. Here we
      investigated how the presence of a plant pathogen, the powdery mildew Erysiphe
      cruciferarum, on Brassica rapa affects (1) plant volatiles emitted in response to
      damage by a specialist herbivore, Pieris brassicae; (2) the attraction of the
      parasitic wasp Cotesia glomerata and (3) the performance of P. brassicae and C.
      glomerata. Plant volatiles were significantly induced by herbivory in both
      healthy and mildew-infected plants, but were quantitatively 41% lower for mildew
      infected plants compared to healthy plants. Parasitoids strongly preferred Pieris
      infested plants to dually-infested (Pieris + mildew) plants, and preferred dually
      infested plants over only mildew-infected plants. The performance of P. brassicae
      was unaffected by powdery mildew, but C. glomerata cocoon mass was reduced when
      parasitized caterpillars developed on mildew-infected plants. Thus, avoidance of
      mildew-infested plants may be adaptive for C. glomerata parasitoids, whereas P.
      brassicae caterpillars may suffer less parasitism on mildew-infected plants in
      nature. From a pest management standpoint, the concurrent presence of multiple
      plant antagonists can affect the efficiency of specific natural enemies, which
      may in turn have a negative impact on the regulation of pest populations.

PMID- 27043840
TI  - Surgeon preferences regarding antibiotic prophylaxis for ballistic fractures.
AB  - BACKGROUND: Scant evidence exists to support antibiotic use for low velocity
      ballistic fractures (LVBF). We therefore sought to define current practice
      patterns. We hypothesized that most surgeons prescribe antibiotics for LVBF,
      prescribing is not driven by institutional protocols, and that decisions are
      based on protocols utilized for blunt trauma. MATERIALS AND METHODS: A web-based
      questionnaire was emailed to the membership of the Orthopaedic Trauma Association
      (OTA). The questionnaire included demographic information and questions about
      LVBF treatment practices. Two hundred and twenty surgeons responded. One hundred
      and fifty-four (70 %) respondents worked at a Level-1 trauma center, 176 (80 %)
      had received fellowship education in orthopaedic trauma and 104 (47 %) treated at
      least 10 ballistic fractures annually. Responses were analyzed with SAS 9.3 for
      Windows (SAS Institute Inc, Cary, NC). RESULTS: One hundred eighty-six
      respondents (86 %) routinely provide antibiotics for LVBF. Those who did not were
      more apt to do so for intra-articular fractures (8/16, 50 %) and pelvic fractures
      with visceral injury (10/16, 63 %). Most surgeons (167, 76 %) do not believe the
      Gustilo-Anderson classification applies to ballistic fractures, and (20/29, 70 %)
      do not base their antibiotic choice on the classification system. Few
      institutions (58, 26 %) have protocols guiding antibiotic use for LVBF.
      CONCLUSIONS: Routine antibiotic use for LVBF is common; however, practice is not
      dictated by institutional protocol. Although antibiotic use generally follows
      current blunt trauma guidelines, surgeons do not base their treatment decisions
      the Gustilo-Anderson classification. Given the high rate of antibiotic use for
      LVBF, further study should focus on providing evidence-based treatment
      guidelines.

PMID- 27043841
TI  - A Pharmacogenetic Study of Psoriasis Risk Variants in a Greek Population and
      Prediction of Responses to Anti-TNF-alpha and Anti-IL-12/23 Agents.
AB  - INTRODUCTION: Psoriasis is a highly divergent disease with many disease
      phenotypes, but there are currently no established biomarkers to predict the
      therapeutic outcomes of systemic treatments. With the introduction of biologic
      therapies during the last decade and with new treatments constantly emerging,
      there is a great need to validate biomarkers that have been reported to be
      associated with treatment response, and to introduce new biomarkers of possible
      clinical value. METHODS: In the current study, we aimed to investigate the
      association of psoriasis-related polymorphisms that have previously been reported
      to effect the anti-tumor necrosis factor alpha (anti-TNF-alpha) therapies
      (etanercept, adalimumab, and infliximab) and anti-interleukin-12/23 (anti-IL
      12/23) biologic therapy (ustekinumab) in a Greek cohort of psoriasis patients.
      RESULTS: Rs10484554 in the HLA-C gene showed an association with a good response
      to anti-TNF-alpha agents but not to ustekinumab, while rs151823 and rs26653 in
      the ERAP1 gene showed associations with a good response to anti-IL-12/23 therapy.
      CONCLUSION: This study is the first in the field of pharmacogenetics in Greek
      psoriasis patients. Further, larger studies are required to validate our findings
      and replicate them in various populations.

PMID- 27043842
TI  - Interactions of Hydrogen Molecules with Halogen-Containing Diatomics from Ab
      Initio Calculations: Spherical-Harmonics Representation and Characterization of
      the Intermolecular Potentials.
AB  - For the prototypical diatomic-molecule-diatomic-molecule interactions H2-HX and
      H2-X2, where X = F, Cl, Br, quantum-chemical ab initio calculations are carried
      out on grids of the configuration space, which permit a spherical-harmonics
      representation of the potential energy surfaces (PESs). Dimer geometries are
      considered for sets of representative leading configurations, and the PESs are
      analyzed in terms of isotropic and anisotropic contributions. The leading
      configurations are individuated by selecting a minimal set of mutual orientations
      of molecules needed to build the spherical-harmonic expansion on geometrical and
      symmetry grounds. The terms of the PESs corresponding to repulsive and bonding
      dimer geometries and the averaged isotropic term, for each pair of interacting
      molecules, are compared with representations in terms of a potential function
      proposed by Pirani et al. (see Chem. Phys. Lett. 2004, 394, 37-44 and references
      therein). Connections of the involved parameters with molecular properties
      provide insight into the nature of the interactions. 

PMID- 27043843
TI  - Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in
      Hashimoto's thyroiditis.
AB  - Vitamin D deficiency and/or reduced function, as per certain polymorphisms of the
      vitamin D receptor (VDR) gene, have been related to several autoimmune disorders.
      The present study was aimed to investigate the association of Hashimoto's
      thyroiditis with vitamin D status and functional polymorphisms (SNPs) of the VDR
      gene. In this case-control study, 200 euthyroid subjects were enrolled: 100 newly
      diagnosed HT patients (87 F, 13 M; mean age +/- SD 42 +/- 15 year) and 100
      healthy individuals, matched for age, sex, BMI, and month of blood sampling.
      Serum 25(OH)D3 was measured by HPLC. The VDR SNPs BsmI, ApaI, and TaqI, in strong
      linkage disequilibrium with each other, were detected by restriction fragment
      length polymorphism-PCR. The prevalence of vitamin D deficiency in HT patients
      was significantly higher than that in the control group (70 vs 18.2 %; p <
      0.0001), and median serum 25(OH)D3 level was significantly lower in HT patients
      than controls (median value: 16.2 vs 37.4 ng/ml; p = 0.026). Moreover, there was
      a significant inverse correlation between serum 25(OH)D3 and TPOAb concentration
      (r = -0.669; p = 0.034). Contrarily, the genotype distribution of the studied
      SNPs was not different in the two groups (BsmI p = 0.783; ApaI p = 0.512; TaqI p
      = 0.471), as was the allelic frequency [f(B) p = 0.776, f(b) p = 0.887; f(A) p =
      0.999, f(a) p = 0.999; f(T) p = 0.617; f(t) p = 0.617]. The present study first
      investigates newly diagnosed untreated HT and suggests that vitamin D deficiency
      may contribute to HT development and/or progression, acting as an environmental
      trigger, while the VDR locus does not appear to be involved in conditioning the
      genetic susceptibility to the disease, at least in Caucasians.

PMID- 27043844
TI  - Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a Patient
      Taking Biotin Megadoses.
AB  - BACKGROUND: Accurate immunoassays measuring minute quantities of hormones are the
      cornerstone of the practice of endocrinology. Despite tremendous advances in this
      field, novel pitfalls in these tests emerge from time to time. Oral biotin can
      interfere with immunoassays of several hormones. The purpose of this report is to
      relate an extreme case of such interference. PATIENT FINDINGS: A patient with
      progressive multiple sclerosis was found to have extremely elevated free
      thyroxine, triiodothyronine, and suppressed thyrotropin (TSH) levels. His TSH
      receptor binding inhibiting antibody level was also elevated. This constellation
      of laboratory findings suggested a diagnosis of severe Graves' disease. All of
      the assays yielding abnormal results employed the biotin-streptavidin affinity in
      their design. The patient had no symptoms of hyperthyroidism, and detailed review
      of his medications revealed intake of megadoses of biotin. Temporary
      discontinuation of biotin treatment resulted in complete resolution of the
      biochemical abnormalities. CONCLUSIONS: Non-physiologic biotin supplementation
      may interfere with several immunoassays, including thyroid hormones, TSH,
      thyroglobulin, and TSH receptor binding inhibiting antibody, leading to erroneous
      diagnoses. Questioning for biotin intake should be part of the evaluation for
      patients undergoing endocrine tests. Interruption of biotin supplementation for
      at least two days prior to biotin-sensitive tests should be sufficient to avoid
      major misdiagnoses.

PMID- 27043845
TI  - The health status and well-being of low-resource, housing-unstable, single-parent
      families living in violent neighbourhoods in Philadelphia, Pennsylvania.
AB  - The health and well-being of single-parent families living in violent
      neighbourhoods in US cities who participate in housing programmes is not well
      described. This two-phase, mixed-methods study explores the health status of
      families who were participants in a housing-plus programme in Philadelphia,
      Pennsylvania between 2011 and 2013 and the relationship between the
      characteristics of the neighbourhoods in which they lived and their perceptions
      of well-being and safety. In phase 1, data collected with standardised health
      status instruments were analysed using descriptive statistics and independent
      sample t-tests to describe the health of single parents and one randomly selected
      child from each parent's household in comparison to population norms. In a subset
      of survey respondents, focus groups were conducted to generate an in-depth
      understanding of the daily lives and stressors of these families. Focus group
      data were analysed using content analysis to identify key descriptive themes. In
      phase 2, daily activity path mapping, surveys and interviews of parent-child
      dyads were collected to assess how these families perceive their health,
      neighbourhood and the influence of neighbourhood characteristics on the families'
      day-to-day experience. Narratives and activity maps were combined with crime data
      from the Philadelphia Police Department to analyse the relationship between crime
      and perceptions of fear and safety. Phase 1 data demonstrated that parent
      participants met or exceeded the national average for self-reported physical
      health but fell below the national average across all mental health domains. Over
      40% reported moderate to severe symptoms of depression. Parents described high
      levels of stress resulting from competing priorities, financial instability, and
      concern for their children's well-being and safety. Analysis of phase 2 data
      demonstrated that neighbourhood characteristics exert influence over parents'
      perceptions of their environment and how they permit their children to move
      within it. This research suggests the need for robust research, programmatic and
      policy interventions to support housing-unstable families who live in
      neighbourhoods with high levels of violence.

PMID- 27043846
TI  - Urgent need for validated trauma and mental health screening tools for refugee
      children and youth.

PMID- 27043847
TI  - The safety and efficacy of trabectedin for the treatment of liposarcoma or
      leiomyosarcoma.
AB  - The improvement of molecular knowledge has highlighted the prognostic and
      predictive significance of histological subtypes in soft tissue sarcoma (STS).
      Here we focus on trabectedin, a drug characterized by a unique action combining
      cytotoxic and target effects. We retraced its main steps of development and
      peculiarities regarding mechanism of action, efficacy and safety especially
      towards liposarcoma and leiomyosarcoma and we compared it against the leading
      therapeutic alternatives with the aim to answer some practical questions such as:
      who and when to treat with trabectedin? For how long? What is the safety profile?
      When should trabectedin be preferred to other treatment options? Finally, we
      provided our viewpoint on how the scenario might evolve in the coming years
      particularly about the 'place' of trabectedin in the therapeutic algorithm and
      its future possible use in combination with other agents in order to achieve even
      more satisfactory results in STS management. 

PMID- 27043848
TI  - Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A
      Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with
      Major Depressive Disorder.
AB  - BACKGROUND: It is unclear whether antidepressants can prevent suicides or suicide
      attempts, particularly during long-term use. METHODS: We carried out a
      comprehensive review of long-term studies of antidepressants (relapse
      prevention). Sources were obtained from 5 review articles and by searches of
      MEDLINE, PubMed Central and a hand search of bibliographies. We meta-analyzed
      placebo-controlled antidepressant RCTs of at least 3 months' duration and
      calculated suicide and suicide attempt incidence rates, incidence rate ratios and
      Peto odds ratios (ORs). RESULTS: Out of 807 studies screened 29 were included,
      covering 6,934 patients (5,529 patient-years). In total, 1.45 suicides and 2.76
      suicide attempts per 1,000 patient-years were reported. Seven out of 8 suicides
      and 13 out of 14 suicide attempts occurred in antidepressant arms, resulting in
      incidence rate ratios of 5.03 (0.78-114.1; p = 0.102) for suicides and of 9.02
      (1.58-193.6; p = 0.007) for suicide attempts. Peto ORs were 2.6 (0.6-11.2;
      nonsignificant) and 3.4 (1.1-11.0; p = 0.04), respectively. Dropouts due to
      unknown reasons were similar in the antidepressant and placebo arms (9.6 vs.
      9.9%). The majority of suicides and suicide attempts originated from 1 study,
      accounting for a fifth of all patient-years in this meta-analysis. Leaving out
      this study resulted in a nonsignificant incidence rate ratio for suicide attempts
      of 3.83 (0.53-91.01). CONCLUSIONS: Therapists should be aware of the lack of
      proof from RCTs that antidepressants prevent suicides and suicide attempts. We
      cannot conclude with certainty whether antidepressants increase the risk for
      suicide or suicide attempts. Researchers must report all suicides and suicide
      attempts in RCTs.

PMID- 27043849
TI  - Quality and exploitation of umbilical cord blood for cell therapy: Are we beyond
      our capabilities?
AB  - There is increasing interest in identifying novel stem cell sources for
      application in emerging cell therapies. In this context, umbilical cord blood
      (UCB) shows great promise in multiple clinical settings. The number of UCB banks
      has therefore increased worldwide, with the objective of preserving potentially
      life-saving cells that are usually discarded after birth. After a rather long and
      costly processing procedure, the resultant UCB-derived cell products are
      cryopreserved until transplantation to patients. However, in many cases, only a
      small proportion of administered cells engraft successfully. Thus, can we do any
      better regarding current UCB-based therapeutic approaches? Here we discuss
      concerns about the use of UCB that are not critically pondered by researchers,
      clinicians, and banking services, including wasting samples with small volumes
      and the need for more reliable quality and functional controls to ensure the
      biological activity of stem cells and subsequent engraftment and treatment
      efficacy. Finally, we appeal for collaborative agreements between research
      institutions and UCB banks in order to redirect currently discarded small-volume
      UCB units for basic and clinical research purposes. Developmental Dynamics
      245:710-717, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27043850
TI  - Simultaneous EEG-fMRI for working memory of the human brain.
AB  - Memory plays an important role in human life. Memory can be divided into two
      categories, i.e., long term memory and short term memory (STM). STM or working
      memory (WM) stores information for a short span of time and it is used for
      information manipulations and fast response activities. WM is generally involved
      in the higher cognitive functions of the brain. Different studies have been
      carried out by researchers to understand the WM process. Most of these studies
      were based on neuroimaging modalities like fMRI, EEG, MEG etc., which use
      standalone processes. Each neuroimaging modality has some pros and cons. For
      example, EEG gives high temporal resolution but poor spatial resolution. On the
      other hand, the fMRI results have a high spatial resolution but poor temporal
      resolution. For a more in depth understanding and insight of what is happening
      inside the human brain during the WM process or during cognitive tasks, high
      spatial as well as high temporal resolution is desirable. Over the past decade,
      researchers have been working to combine different modalities to achieve a high
      spatial and temporal resolution at the same time. Developments of MRI compatible
      EEG equipment in recent times have enabled researchers to combine EEG-fMRI
      successfully. The research publications in simultaneous EEG-fMRI have been
      increasing tremendously. This review is focused on the WM research involving
      simultaneous EEG-fMRI data acquisition and analysis. We have covered the
      simultaneous EEG-fMRI application in WM and data processing. Also, it adds to
      potential fusion methods which can be used for simultaneous EEG-fMRI for WM and
      cognitive tasks. 

PMID- 27043851
TI  - Re: Complex link between male lower urinary tract symptoms and metabolic
      syndrome: More than ethnic disparity.

PMID- 27043852
TI  - Improving the Accuracy of Daily PM2.5 Distributions Derived from the Fusion of
      Ground-Level Measurements with Aerosol Optical Depth Observations, a Case Study
      in North China.
AB  - The accuracy in estimated fine particulate matter concentrations (PM2.5),
      obtained by fusing of station-based measurements and satellite-based aerosol
      optical depth (AOD), is often reduced without accounting for the spatial and
      temporal variations in PM2.5 and missing AOD observations. In this study, a city
      specific linear regression model was first developed to fill in missing AOD data.
      A novel interpolation-based variable, PM2.5 spatial interpolator (PMSI2.5), was
      also introduced to account for the spatial dependence in PM2.5 across grid cells.
      A Bayesian hierarchical model was then developed to estimate spatiotemporal
      relationships between AOD and PM2.5. These methods were evaluated through a city
      specific 10-fold cross-validation procedure in a case study in North China in
      2014. The cross validation R(2) was 0.61 when PMSI2.5 was included and 0.48 when
      PMSI2.5 was excluded. The gap-filled AOD values also effectively improved
      predicted PM2.5 concentrations with an R(2) = 0.78. Daily ground-level PM2.5
      concentration fields at a 12 km resolution were predicted with complete spatial
      and temporal coverage. This study also indicates that model prediction
      performance should be assessed by accounting for monitor clustering due to the
      potential misinterpretation of model accuracy in spatial prediction when
      validation monitors are randomly selected.

PMID- 27043853
TI  - Pain after breast surgery: Etiology, diagnosis, and definitive management.
AB  - BACKGROUND: Breast procedures are among the most common surgeries performed by
      Plastic Surgeons. The prevalence of persistent pain remains unknown. Our
      experience has been that persistent breast pain is often related to intercostal
      nerve trauma. The purpose of this article was to increase awareness of this
      problem while describing the diagnostic and management strategies for patients
      with post-operative breast pain. METHODS: A retrospective review of 10 patients
      with breast pain was stratified according to the index surgical procedures:
      implant-based reconstruction (7), breast reduction (1), breast augmentation (1),
      and mastopexy (1). Outcomes were assessed with a numerical analog score. Physical
      examination demonstrated painful trigger points along the pathway of one or more
      intercostal nerves. Prior to surgery, each patient improved >=5 points after a
      diagnostic Xylocaine/Marcaine local anesthesia block of the suspected intercostal
      nerves. At surgery, one or more intercostal nerves were resected and implanted
      into adjacent muscles. RESULTS: At a mean of 16.5 months, there were six
      excellent, one good, and three poor self-reported results. Intercostal nerves
      resected included the intercostal-brachial (5 patients), 3rd (7 patients), 4th (8
      patients), 5th (9 patients), 6th (7 patients), and 7th (1 patient). Multiple
      intercostal nerves were resected as follows: 3 nerves (4 patients), 4 nerves (1
      patient), 5 nerves (3 patients), 6 nerves (1 patient), and 8 nerves (1 patient).
      CONCLUSIONS: Intercostal neuromas can be the source of breast pain following
      breast surgery. The same clinical and diagnostic approach used for upper and
      lower extremity neuroma pain can be used in patients with breast pain. (c) 2016
      Wiley Periodicals, Inc. Microsurgery 36:535-538, 2016.

PMID- 27043854
TI  - Gender and asthma-chronic obstructive pulmonary disease overlap syndrome.
AB  - OBJECTIVE: To assess relationships between obstructive lung diseases, respiratory
      symptoms, and comorbidities by gender. METHODS: Data from 12 594 adult
      respondents to the 2012 South Carolina Behavioral Risk Factor Surveillance System
      telephone survey were used. Five categories of chronic obstructive airway disease
      (OAD) were defined: former asthma only, current asthma only, chronic obstructive
      pulmonary disease (COPD) only, asthma-COPD overlap syndrome (ACOS), and none.
      Associations of these categories with respiratory symptoms (frequent productive
      cough, shortness of breath, and impaired physical activities due to breathing
      problems), overall health, and comorbidities were assessed using multivariable
      logistic regression for men and women. RESULTS: Overall, 16.2% of men and 18.7%
      of women reported a physician diagnosis of COPD and/or asthma. Former asthma only
      was higher among men than women (4.9% vs. 3.2%, t-test p = 0.008). Current asthma
      only was more prevalent among women than men (7.2% vs. 4.7%, p < 0.001), as was
      ACOS (4.0% vs. 2.2%, p < 0.001). Having COPD only did not differ between women
      (4.3%) and men (4.4%). Adults with ACOS were most likely to report the 3
      respiratory symptoms. COPD only and ACOS were associated with higher likelihoods
      of poor health and most comorbidities for men and women. Current asthma only was
      also associated with these outcomes among women, but not among men. CONCLUSIONS:
      In this large population-based sample, women were more likely than men to report
      ACOS and current asthma, but not COPD alone. Gender differences were evident
      between the OAD groups in sociodemographic characteristics, respiratory symptoms,
      and comorbidities, as well as overall health.

PMID- 27043855
TI  - Love, Lust, and Loss in the Early Age of AIDS: The Discourse in the Body Politic
      From 1981 to 1987.
AB  - This article explores the idea that the AIDS epidemic constituted a defining
      moment for the Canadian gay rights movement and illuminates the intricate power
      dynamics of the development of a community identity. Using grounded theory
      inductive and deductive content analysis, and interviews with activists from the
      Body Politic magazine, this article considers notions of health "from above" and
      "from below" by examining relations between the community and government and
      their confrontation with medicalization and the medical profession. I also
      examine how the magazine reported and negotiated issues related to the
      community's self-policing and "self-managed oppression" through efforts to
      promote safer sex and risk reduction.

PMID- 27043856
TI  - Edge density based automatic detection of inflammation in colonoscopy videos.
AB  - Colon cancer is one of the deadliest diseases where early detection can prolong
      life and can increase the survival rates. The early stage disease is typically
      associated with polyps and mucosa inflammation. The often used diagnostic tools
      rely on high quality videos obtained from colonoscopy or capsule endoscope. The
      state-of-the-art image processing techniques of video analysis for automatic
      detection of anomalies use statistical and neural network methods. In this paper,
      we investigated a simple alternative model-based approach using texture analysis.
      The method can easily be implemented in parallel processing mode for real-time
      applications. A characteristic texture of inflamed tissue is used to distinguish
      between inflammatory and healthy tissues, where an appropriate filter kernel was
      proposed and implemented to efficiently detect this specific texture. The basic
      method is further improved to eliminate the effect of blood vessels present in
      the lower part of the descending colon. Both approaches of the proposed method
      were described in detail and tested in two different computer experiments. Our
      results show that the inflammatory region can be detected in real-time with an
      accuracy of over 84%. Furthermore, the experimental study showed that it is
      possible to detect certain segments of video frames containing inflammations with
      the detection accuracy above 90%. 

PMID- 27043857
TI  - PDB2Graph: A toolbox for identifying critical amino acids map in proteins based
      on graph theory.
AB  - The integrative and cooperative nature of protein structure involves the
      assessment of topological and global features of constituent parts. Network
      concept takes complete advantage of both of these properties in the analysis
      concomitantly. High compatibility to structural concepts or physicochemical
      properties in addition to exploiting a remarkable simplification in the system
      has made network an ideal tool to explore biological systems. There are numerous
      examples in which different protein structural and functional characteristics
      have been clarified by the network approach. Here, we present an interactive and
      user-friendly Matlab-based toolbox, PDB2Graph, devoted to protein structure
      network construction, visualization, and analysis. Moreover, PDB2Graph is an
      appropriate tool for identifying critical nodes involved in protein structural
      robustness and function based on centrality indices. It maps critical amino acids
      in protein networks and can greatly aid structural biologists in selecting proper
      amino acid candidates for manipulating protein structures in a more reasonable
      and rational manner. To introduce the capability and efficiency of PDB2Graph in
      detail, the structural modification of Calmodulin through allosteric binding of
      Ca(2+) is considered. In addition, a mutational analysis for three well
      identified model proteins including Phage T4 lysozyme, Barnase and Ribonuclease
      HI, was performed to inspect the influence of mutating important central residues
      on protein activity.

PMID- 27043858
TI  - Rhythm-based heartbeat duration normalization for atrial fibrillation detection.
AB  - BACKGROUND: Screening of atrial fibrillation (AF) for high-risk patients
      including all patients aged 65 years and older is important for prevention of
      risk of stroke. Different technologies such as modified blood pressure monitor,
      single lead ECG-based finger-probe, and smart phone using plethysmogram signal
      have been emerging for this purpose. All these technologies use irregularity of
      heartbeat duration as a feature for AF detection. We have investigated a
      normalization method of heartbeat duration for improved AF detection. METHOD: AF
      is an arrhythmia in which heartbeat duration generally becomes irregularly
      irregular. From a window of heartbeat duration, we estimate the possible rhythm
      of the majority of heartbeats and normalize duration of all heartbeats in the
      window based on the rhythm so that we can measure the irregularity of heartbeats
      for both AF and non-AF rhythms in the same scale. Irregularity is measured by the
      entropy of distribution of the normalized duration. Then we classify a window of
      heartbeats as AF or non-AF by thresholding the measured irregularity. The effect
      of this normalization is evaluated by comparing AF detection performances using
      duration with the normalization, without normalization, and with other existing
      normalizations. RESULTS: Sensitivity and specificity of AF detection using
      normalized heartbeat duration were tested on two landmark databases available
      online and compared with results of other methods (with/without normalization) by
      receiver operating characteristic (ROC) curves. ROC analysis showed that the
      normalization was able to improve the performance of AF detection and it was
      consistent for a wide range of sensitivity and specificity for use of different
      thresholds. Detection accuracy was also computed for equal rates of sensitivity
      and specificity for different methods. Using normalized heartbeat duration, we
      obtained 96.38% accuracy which is more than 4% improvement compared to AF
      detection without normalization. CONCLUSIONS: The proposed normalization method
      was found useful for improving performance and robustness of AF detection.
      Incorporation of this method in a screening device could be crucial to reduce the
      risk of AF-related stroke. In general, the incorporation of the rhythm-based
      normalization in an AF detection method seems important for developing a robust
      AF screening device.

PMID- 27043859
TI  - Anti-inflammatory TIPE2 inhibits angiogenic VEGF in retinal pigment epithelium.
AB  - Choroidal neovascularization (CNV) is a pathological feature which commonly
      occurs in ocular diseases. This condition is characterised by vasculogenesis and
      angiogenesis underlying the neuroretina, with retinal pigment epithelium (RPE)
      and choroid as main targets. Inflammation and immunity are crucial in the early
      development of CNV. Tumour necrosis factor (TNF) alpha-induced protein-8 like-2
      (TIPE2 or TNFAIP8L2), a recently identified gene, is a negative regulator of
      innate and adaptive immunity which participates in inflammatory homeostasis. We
      determined the expression of TIPE2 in normal and inflamed RPE cells, and
      evaluated the relationship of TIPE2 with factors associated with inflammation and
      angiogenesis. TIPE2 is present in both the cytoplasm and nucleus of human RPE
      cells and is down-regulated in the inflammatory state with decreased cell
      viability. Knock-down of TIPE2 by a specific short interfering RNA increases the
      expression levels of TNF-alpha, IL-1beta and angiogenic vascular endothelial
      growth factor (VEGF), particularly under the stimulation of lipopolysaccharide.
      In consideration of the vital role of VEGF in the final stage of
      neovascularization, the anti-inflammatory TIPE2 is also anti-angiogenic and may
      participate in CNV formation.

PMID- 27043860
TI  - Persimmon vinegar and its fractions protect against alcohol-induced hepatic
      injury in rats through the suppression of CYP2E1 expression.
AB  - CONTEXT: Medical therapies for alcohol-induced liver disease are often difficult
      to handle and limited in efficacy. OBJECTIVE: In an attempt to find natural
      therapeutics, here, we investigate the preventive effect of persimmon vinegar
      (PV) and its fractions against alcohol-induced hepatic injury, in addition to the
      underlying mechanism, in rats chronically administered with alcohol. MATERIALS
      AND METHODS: Forty male Wistar rats were randomized into five groups (n = 8 per
      group); normal control (NC), ethanol control (EC), ethanol + PV, ethanol + water
      insoluble PV fraction (PI) and ethanol + water-soluble PV fraction (PS). PV, PI
      or PS was orally administrated at the level of 100 mg/kg B.W by oral gavage every
      day for 4 weeks prior to ethanol administration. The liver sections were stained
      with hematoxylin & eosin and gene expression was assessed by real-time polymerase
      chain reaction. RESULTS: After a 4-week treatment, histological observation
      revealed that PV and its fractions mitigated alcohol-induced changes in the
      liver. CYP2E1 expression was significantly increased in the EC group compared
      with the NC group, but was significantly suppressed in the PV group compared with
      the EC group (p = 0.044). We also found significant decreases in hepatic mRNA
      expression of interleukin (IL)-1beta, IL-12beta, toll-like receptor (TLR)-4 and
      cyclooxygenase (COX)-2 in the PV-, PI- and PS-treated groups compared with those
      of the EC group. DISCUSSION AND CONCLUSION: Taken together, the present findings
      suggest that PV and its fractions hold great promise as natural remedies with
      anti-inflammatory activities that alleviate alcohol-induced liver damage.

PMID- 27043861
TI  - Improving the postpartum care of women with a recent history of preeclampsia: a
      focus group study.
AB  - OBJECTIVE: Women with prior preeclampsia are at increased risk of cardiovascular
      disease (CVD). This study investigated barriers and facilitators toward learning
      about this link and engaging in lifestyle modifications to reduce this risk.
      METHODS: Four focus groups were held with 14 women within 6 months of a
      preeclamptic pregnancy. RESULTS: Participants were unaware of the link between
      preeclampsia and CVD, suggested improvements to provider-patient communication,
      and discussed the benefits of social support and online tracking (weight, blood
      pressure) in making lifestyle modifications. CONCLUSIONS: Solutions offered may
      improve efforts to modify lifestyle and communication between providers and women
      about this link.

PMID- 27043862
TI  - Intraoperative Endoscopic Botox Injection During Total Esophagectomy Prevents the
      Need for Pyloromyotomy or Dilatation.
AB  - BACKGROUND: Esophagectomy may lead to impairment in gastric emptying unless
      pyloric drainage is performed. Pyloric drainage may be technically challenging
      during minimally invasive esophagectomy and can add morbidity. We sought to
      determine the effectiveness of intraoperative endoscopic injection of botulinum
      toxin into the pylorus during robotic-assisted esophagectomy as an alternative to
      surgical pyloric drainage. MATERIALS AND METHODS: We performed a retrospective
      analysis of patients with adenocarcinoma and squamous cell carcinoma of the
      distal esophagus or gastroesophageal junction who underwent robotic-assisted
      transhiatal esophagectomy (RATE) without any surgical pyloric drainage. Patients
      with and without intraoperative endoscopic injection of 200 units of botulinum
      toxin in 10 cc of saline (BOTOX group) were compared to those that did not
      receive any pyloric drainage (noBOTOX group). Main outcome measure was the
      incidence of postoperative pyloric stenosis; secondary outcomes included
      operative and oncologic parameters, length of stay (LOS), morbidity, and
      mortality. RESULTS: From November 2006 to August 2014, 41 patients (6 females)
      with a mean age of 65 years underwent RATE without surgical drainage of the
      pylorus. There were 14 patients in the BOTOX group and 27 patients in the noBOTOX
      group. Mean operative time was not different between the comparison groups. There
      was one conversion to open surgery in the BOTOX group. No pyloric dysfunction
      occurred in the BOTOX group postoperatively, and eight stenoses in the noBOTOX
      group (30%) required endoscopic therapy (P < .05). There were no differences in
      incidence of anastomotic strictures or anastomotic leaks. One patient in group
      noBOTOX required pyloroplasty 3 months after esophagectomy. There was one death
      in the noBOTOX group postoperatively (30-day mortality 2.4%). Mean LOS was 9.6
      days, and BOTOX patients were discharged earlier (7.4 versus 10.7, P < .05).
      CONCLUSION: Intraoperative endoscopic injection of botulinum toxin into the
      pylorus during RATE is feasible, safe, and effective and can prevent the need for
      pyloromyotomy.

PMID- 27043863
TI  - Hepatitis B control among children in the Eastern Mediterranean Region of the
      World Health Organization.
AB  - In the pre-vaccination era, the prevalence of chronic hepatitis B virus (HBV)
      infection in the World Health Organization (WHO) Eastern Mediterranean Region
      (EMR) ranged from two to seven percent in a total population of over 580 million
      people. Mortality estimates place cirrhosis among the top ten causes of years of
      life lost in the EMR. The region has made notable achievements, improving
      coverage from only 6% in 1992, when WHO recommended hepatitis B vaccination of
      all infants, to 83% in 2014. Member states adopted a hepatitis B control target
      in 2009 to reduce chronic hepatitis B virus infection prevalence to less than one
      percent among children aged <5 years by 2015. This report reviews progress toward
      achievement, challenges faced, and the next steps forward of hepatitis B control
      among children in the EMR.

PMID- 27043864
TI  - Hepatitis B birth dose vaccination rates among children in Beijing: A comparison
      of local residents and first and second generation migrants.
AB  - Providing hepatitis B vaccine to all neonates within 24 hours of birth (Timely
      Birth Dose, TBD) is the key preventative measure to control perinatal hepatitis B
      virus infection. Previous Chinese studies of TBD only differentiated between
      migrant and non-migrant (local-born generation-LG) children. Our study is the
      first to stratify migrants in Beijing into first generation migrants (FGM) and
      second generation migrants (SGM). Based on a questionnaire survey of 2682 people
      in 3 Beijing villages, we identified 283 children aged 0-15 years, from 246
      households, who were eligible for a TBD. Multinomial logistic regression and
      statistical analyses were used to examine factors explaining TBD rates for LG,
      FGM and SGM children. Surprisingly, the TBD for LG Beijing children was not
      significantly different from migrant children. But after stratifying migrant
      children into FGM and SGM, revealed significant TBD differences were revealed
      across LG, FGM and SGM according to domicile (p-value < 0.001, OR = 3.24), first
      vaccination covered by government policy (p-value < 0.05, OR = 3.24), mother's
      knowledge of hepatitis B (p-value < 0.05, OR = 1.01) and the government's HBV
      policy environment (p-value < 0.05, OR = 2.338). Birthplace (p-value = 0.002, OR
      = 6.21) and better policy environments (p-value = 0.01, OR = 2.80) were
      associated with higher TBD rate for LG and SGM children. Compared with FGM
      children, SGM had a significantly poorer TBD rate (Fisher exact test of chi
      square = 0.013). We identified SGM as a special risk group; proposed Hukou reform
      to improve SGM TBD; and called for Beijing health authorities to match TBD rates
      in other provinces, especially by improving practices by health authorities and
      knowledge of parents.

PMID- 27043865
TI  - Trends in mouth cancer incidence in Mumbai, India (1995-2009): An age-period
      cohort analysis.
AB  - INTRODUCTION: Despite tobacco control and health promotion efforts, the incidence
      rates of mouth cancer are increasing across most regions in India. Analysing the
      influence of age, time period and birth cohort on these secular trends can point
      towards underlying factors and help identify high-risk populations for improved
      cancer control programmes. METHODS: We evaluated secular changes in mouth cancer
      incidence among men and women aged 25-74 years in Mumbai between 1995 and 2009 by
      calculating age-specific and age-standardized incidence rates (ASR). We estimated
      the age-adjusted linear trend for annual percent change (EAPC) using the drift
      parameter, and conducted an age-period-cohort (APC) analysis to quantify recent
      time trends and to evaluate the significance of birth cohort and calendar period
      effects. RESULTS: Over the 15-year period, age-standardized incidence rates of
      mouth cancer in men in Mumbai increased by 2.7% annually (95% CI:1.9 to 3.4),
      p<0.0001) while rates among women decreased (EAPC=-0.01% (95% CI:-0.02 to 
      0.002), p=0.03). APC analysis revealed significant non-linear positive period and
      cohort effects in men, with higher effects among younger men (25-49 years). Non
      significant increasing trends were observed in younger women (25-49 years).
      CONCLUSIONS: APC analyses from the Mumbai cancer registry indicate a significant
      linear increase of mouth cancer incidence from 1995 to 2009 in men, which was
      driven by younger men aged 25-49 years, and a non-significant upward trend in
      similarly aged younger women. Health promotion efforts should more effectively
      target younger cohorts.

PMID- 27043866
TI  - Characterisation and management of dermatologic adverse events to agents
      targeting the PD-1 receptor.
AB  - BACKGROUND: Dermatologic adverse events (AEs) are some of the most frequently
      observed toxicities of immune-checkpoint inhibitor therapy, but they have
      received little attention. The drugs, pembrolizumab and nivolumab are recently
      approved inhibitors of the programmed death (PD)-1 receptor that have overlapping
      AE profiles however, the incidence, relative risk (RR), and clinico-morphological
      pattern of the associated dermatologic AEs are not known. METHODS: We conducted a
      systematic review of the literature, and performed a meta-analysis of
      dermatologic AEs observed with the use of pembrolizumab and nivolumab in cancer
      patients. An electronic search was conducted using the PubMed, and Web of
      Science, and on the American Society of Clinical Oncology and European Society
      for Medical Oncology meeting abstracts' libraries for potentially relevant
      oncology trials, that employed the drugs at Food and Drug Administration-approved
      doses and reported dermatologic AEs. The incidence, RR and 95% confidence
      intervals were calculated using either random- or fixed-effects models based on
      the heterogeneity of included studies. The clinical presentation, histology of
      affected skin areas, and management strategies (based on institutional
      experience), are also presented. RESULTS: Rash, pruritus and vitiligo were found
      to be the most frequently reported dermatologic AEs. The calculated incidence of
      all-grade rash with pembrolizumab and nivolumab was 16.7% (RR = 2.6) and 14.3%
      (RR = 2.5), respectively. Other significant all-grade AEs included pruritus
      (pembrolizumab: incidence, 20.2% [RR = 49.9]; nivolumab: incidence, 13.2% [RR =
      34.5]) and vitiligo (pembrolizumab: incidence, 8.3% [RR = 17.5]; nivolumab: 7.5%
      [RR = 14.6]). Interestingly, all the vitiligo events were reported in trials
      investigating melanoma. The RR for developing dermatologic AEs in general, was
      2.95 with pembrolizumab, and 2.3 with nivolumab. CONCLUSION: We found that
      pembrolizumab and nivolumab are both associated with dermatologic AEs, primarily
      low-grade rash, pruritus, and vitiligo, which are reminiscent of those seen with
      ipilimumab. Knowledge of these findings is critical for optimal care, maintaining
      dose intensity, and health-related quality of life in cancer patients receiving
      PD-1 inhibitors.

PMID- 27043867
TI  - Primary high-grade soft-tissue sarcoma of the buttock: a rare but distinct
      clinical entity.
AB  - OBJECTIVE: Sarcoma arising in the region of the buttocks is a rare entity and
      therefore no consensus regarding management exists in the literature. METHODS: 16
      patients diagnosed with localized, non-metastatic primary soft-tissue sarcoma
      (STS) in the buttock area, who were consecutively treated between 2005 and 2013,
      were retrospectively evaluated for the rate of local control, distant metastases
      and overall survival. RESULTS: Most tumours were classified as high grade
      (87.5%). The average time between the appearances of symptoms to diagnosis of
      sarcoma was 4.5 months. At the end of the observation period, 7 (44%) patients
      were alive without signs of progressive disease, 37.5% patients died as the
      disease progressed, 13 patients were free of disease and 3 (19%) patients were
      alive with signs of progressive disease. Seven (44%) patients developed local
      recurrence. Six (37.5%) patients developed distant metastases. The lung was the
      most common site of distant failure (four patients); other sites were the liver
      as well as the adrenal gland and kidney (one patient). Four patients had both
      distant and local progression, three patients experienced isolated local
      recurrence and two patients developed isolated distant metastases. 5-year local
      recurrence-free survival was 58% and 5-year distant metastases-free survival was
      63%. CONCLUSION: It is unclear whether to subsume STS of the buttock under the
      rubric of pelvic tumours or tumours of the lower extremity. Either way, STS of
      the buttock seems to be characterized by local control, freedom from distant
      relapse and survival, which is inferior to accepted standards for either pelvic
      or lower extremity sarcomas. To improve this poor outcome, oncologists are
      encouraged to regard sarcoma of the buttock as a distinct clinical entity and to
      devise innovative therapeutic strategies accordingly. ADVANCES IN KNOWLEDGE:
      Sarcoma of the buttock area should possibly be regarded as a distinct entity.

PMID- 27043868
TI  - New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats
      using different natural antioxidants.
AB  - Transforming growth factor-beta (TGF-beta1) enhances the expression of apoptosis
      induced by certain cytokines and oncogenes. Activation of small mother against
      decapentaplegic (Smads) by TGF-beta results in fibrotic, apoptotic processes. PI
      3/AKT focal adhesion kinase-phosphatidylinositol3-kinase (AKT), the mitogen
      activated protein kinase (MAPK) and signal transducer and activator of
      transcription-3 (STAT3) pathways are influence in COX-2 and VEGF-stimulating
      pathways. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that
      regulates an array of detoxifying and antioxidant defense genes expression in the
      liver. The objective of this study is to examine whether silymarin alone or in
      combination with vitamin E and/or curcumin plays a modulatory role against MAPK,
      STAT3, AKT, Smad-2 and TGF-beta protein expressions that produced apoptotic
      damage in rat's liver by the administration of carbon tetrachloride (CCl4). The
      results of the present work revealed that CCl4-induced an elevation of serum
      alanine aminotransferase (ALT) with concomitant increase in MAPK, STAT3, AKT,
      Smad-2 and TGF-beta hepatic protein expression, administration of silymarin alone
      down regulates these expressions. Treatment with vitamin E and/or curcumin along
      with silymarin produced best results in this concern. On the other hand, Nrf2
      protein expression was down regulated by CCl4 whereas concurrent treatment with
      vitamin E and/or curcumin along with silymarin increased this expression. It was
      concluded that CCl4-induced protein expression of apoptotic and fibenorgenic
      factors. Whereas administration of silymarin alone or in combination with vitamin
      E and/or curcumin plays a modulatory role against the previous aforementioned
      apoptotic factors expressions. The use of vitamin E and/or curcumin potentiates
      the anti-apoptotic action of silymarin. So this combination can be used as
      hepatoprotective agent against other hepatotoxic substances. 

PMID- 27043869
TI  - Emotion, gender, and gender typical identity in autobiographical memory.
AB  - Gender differences in the emotional intensity and content of autobiographical
      memory (AM) are inconsistent across studies, and may be influenced as much by
      gender identity as by categorical gender. To explore this question, data were
      collected from 196 participants (age 18-40), split evenly between men and women.
      Participants narrated four memories, a neutral event, high point event, low point
      event, and self-defining memory, completed ratings of emotional intensity for
      each event, and completed four measures of gender typical identity. For self
      reported emotional intensity, gender differences in AM were mediated by
      identification with stereotypical feminine gender norms. For narrative use of
      affect terms, both gender and gender typical identity predicted affective
      expression. The results confirm contextual models of gender identity (e.g.,
      Diamond, 2012 . The desire disorder in research on sexual orientation in women:
      Contributions of dynamical systems theory. Archives of Sexual Behavior, 41, 73
      83) and underscore the dynamic interplay between gender and gender identity in
      the emotional expression of autobiographical memories.

PMID- 27043870
TI  - Synthesis, characterization, DNA/protein interaction and cytotoxicity studies of
      Cu(II) and Co(II) complexes derived from dipyridyl triazole ligands.
AB  - Four different transition metal complexes containing dipyridyl triazole ligands,
      namely [Cu(abpt)2Cl2].2H2O (1), [Cu(abpt)2(ClO4)2] (2),
      [Co2(abpt)2(H2O)2Cl2].Cl2.4H2O (3) and [Co2(Hbpt)2(CH3OH)2(NO3)2] (4) have been
      designed, synthesized and further structurally characterized by X-ray
      crystallography, ESI-MS, elemental analysis, IR and Raman spectroscopy. In these
      complexes, the both ligands act as bidentate ligands with N, N donors. DNA
      binding interactions with calf thymus DNA (ct-DNA) of the ligand and its
      complexes 1~4 were investigated via electronic absorption, fluorescence
      quenching, circular dichroism and viscosity measurements as well as confocal
      Laser Raman spectroscopy. The results show these complexes are able to bind to
      DNA via the non-covalent mode i.e. intercalation and groove binding or
      electrostatic interactions. The interactions with bovine serum albumin (BSA) were
      also studied using UV-Vis and fluorescence spectroscopic methods which indicated
      that fluorescence quenching of BSA by these compounds was the presence of both
      static and dynamic quenching. Moreover, the in vitro cytotoxic effects of the
      complexes against four cell lines SK-OV-3, HL-7702, BEL7404 and NCI-H460 showed
      the necessity of the coordination action on the biological properties on the
      respective complex and that all four complexes exhibited substantial cytotoxic
      activity. 

PMID- 27043871
TI  - Fe-tannic acid complex dye as photo sensitizer for different morphological ZnO
      based DSSCs.
AB  - In this paper we have synthesized different morphological ZnO nanostructures via
      microwave hydrothermal methods at low temperature within a short time. We
      described different morphologies of ZnO at different Zn(NO3)2/KOH mole ratio. The
      ZnO nanostructures were characterized via X-ray diffraction (XRD), field emission
      scanning electron microscopy (FE-SEM) and UV-vis spectrophotometry. All ZnO
      structures have hexagonal wurtzite type structures. The FESEM images showed
      various morphologies of ZnO such as plate, rod and nanoparticles. Dye sensitized
      solar cells have been assembled by these different morphological structures photo
      electrode and tannic acid or Fe-tannic acid complex dye as sensitizer. We have
      achieved at maximum efficiencies of photovoltaic cells prepared with ZnO plate in
      all dye systems. The conversion efficiencies of dye sensitized solar cells are
      0.37% and 1.00% with tannic acid and Fe-tannic acid complex dye, respectively. 

PMID- 27043872
TI  - Effects of single bond-ion and single bond-diradical form on the stretching
      vibration of C=N bridging bond in 4,4'-disubstituted benzylidene anilines.
AB  - Fifty-seven samples of model compounds, 4,4'-disubstituted benzylidene anilines,
      p-X-ArCH=NAr-p-Y were synthesized. Their infrared absorption spectra were
      recorded, and the stretching vibration frequencies nuC=N of the C=N bridging bond
      were determined. New stretching vibration mode was proposed by means of the
      analysis of the factors affecting nuC=N, that is there are mainly three modes in
      the stretching vibration of C=N bond: (I) polar double bond form C=N, (II) single
      bond-ion form C(+)-N(-) and (III) single bond-diradical form C-N. The
      contributions of the forms (I) and (II) to the change of nuC=N can be quantified
      by using Hammett substituent constant (including substituent cross-interaction
      effects between X and Y groups), whereas the contribution of the form (III) can
      be quantified by employing the excited-state substituent constant. The most
      contribution of these three forms is the form (III), the next is the form (II),
      whose contribution difference was discussed with the viewpoint of energy
      requirements in vibration with the form (III) and form (II).

PMID- 27043873
TI  - Synthesis and characterization Bi2O2S thin film via chemical bath deposition at
      low pH.
AB  - Bismuth oxysulfide thin film was prepared using Bi(NO3)3 and Na2S as reactive.
      Since bismuth in the form of bismuth oxide is dissolved into water, bismuth and
      sulfide concentration of the chemical bath is very important. Bismuth oxysulfide
      (Bi2O2S) thin films were produced below pH2. Tested bismuth and sulfide
      concentrations are as follows: 2*10(-1)M, 2*10(-2)M, 2*10(-3)M, 2*10(-4)M bismuth
      and 1*10(-1)M, 1*10(-2)M, 1*10(-3)M, 1*10(-4)M sulfide. The structure of the
      films was examined via X-ray diffraction (XRD). Optical properties, such as
      transmission and absorbance were measured with Ultra violet-visible spectrum, and
      then refractive index and reflectivity were calculated. The pH of chemical bath
      was stabilized below pH of 2 using 13.85mL concentrated nitric acid. Deposition
      time and temperature of the baths were 4h and 30 degrees C. It has been found
      that bismuth and sulfide concentrations affected the structure and thickness of
      the film. Also, optical band gap of the films varied with concentration, parallel
      to the change of the structure and film thickness. 

PMID- 27043874
TI  - Contralateral limb deficit after ACL-reconstruction: an analysis of early and
      late phase of rate of force development.
AB  - The aim of this study was to assess the effect of a unilateral anterior cruciate
      ligament reconstruction (ACLR) on maximum voluntary contraction (MVC) and
      explosive strength of both the involved limb and the uninvolved limb. Nineteen
      male athletes completed a standard isometric testing protocol 4 months post-ACLR,
      while 16 healthy participants served as a control group (CG). The explosive
      strength of the knee extensors and flexors was assessed as RFD obtained from the
      slope of the force-time curves over various time intervals. Both muscle groups of
      the involved limb had significantly lower MVC compared to the uninvolved. The
      involved limb also had significantly lower RFD in the late phase of contraction
      (140-250 ms) for both knee extensors and flexors (P < 0.05). There was no
      difference in MVC between the uninvolved limb and the CG. However, RFD of the
      uninvolved limb was lower compared to CG for both knee extensors (0-180 ms; P <
      0.01) and flexors (0-150 ms; P < 0.05). ACLR leads to lower MVC and explosive
      strength of the involved limb. As a consequence of potential crossover
      (presumably neural-mediated) effects, explosive strength deficits could be
      bilateral, particularly in the early phase of the contraction (<100 ms).

PMID- 27043875
TI  - Effects of warm acclimation on physiology and gonad development in the sea urchin
      Evechinus chloroticus.
AB  - The physiology of the New Zealand sea urchin Evechinus chloroticus was evaluated
      through feeding, respiration, growth and gonad growth in adult animals acclimated
      for 90days at 18 degrees C (annual mean temperature) and 24 degrees C (ambient
      summer temperature (21 degrees C) +3 degrees C). Measured parameters with
      representative rates of assimilation efficiency were used to calculate scope for
      growth (SfG) for each treatment. All physiological parameters were negatively
      affected at 24 degrees C, showing a decrease in feeding rate which coincided with
      negative growth and gonad development at the end of the acclimation period, and a
      decrease in respiration rate suggesting metabolic depression. Histology of gonad
      samples after the acclimation period also showed no gametic material in animals
      acclimated at 24 degrees C. All animals acclimated at 24 degrees C had negative
      growth, differing from the calculated SfG which indicated that the animals had
      sufficient energy for production. The results suggest that calculated SfG in
      echinoderms should be used together with actual measurements of growth in
      individuals as, by itself, SfG may underestimate the actual effect of ocean
      warming when animals are exposed to stressful conditions. Overall, considering
      the total loss of reproductive output observed in E. chloroticus at higher
      temperatures, an increase in seawater temperature could dramatically influence
      the persistence of northern populations of this species, leading to flow-on
      effects in the subtidal ecosystem.

PMID- 27043876
TI  - A Method to Estimate the Size and Characteristics of HIV-positive Populations
      Using an Individual-based Stochastic Simulation Model: Erratum.

PMID- 27043877
TI  - Cell-free production and streamlined assay of cytosol-penetrating antibodies.
AB  - Antibodies that target intracellular proteins hold great promise in the
      development of novel therapeutic interventions for various diseases. In
      particular, antibodies that can cross cellular membranes have potential
      applications in controlling disease-related intracellular protein-protein
      interactions. Given the large number of cytosolic proteins and complicated
      interactions that are potentially involved in disease development, discovery of
      antibodies targeting intracellular proteins requires iterative cycles of
      expression and assessment of candidate antibodies. Because current cell-based
      expression methods do not provide sufficient throughput for production and assay
      of cytosol-penetrating antibodies, we integrated a cell-free protein synthesis
      system designed to provide optimal conditions for production of functional
      antibodies with a cytosol-penetration assay. The proposed approach of
      consolidating cell-free synthesis and cell-based assay will substantially expand
      the capability of discovering and engineering antibodies that can cross the cell
      membrane and effectively control protein-mediated cellular functions. Biotechnol.
      Bioeng. 2016;113: 2107-2112. (c) 2016 Wiley Periodicals, Inc.

PMID- 27043878
TI  - The future direction and unmet needs of transplant immunosuppression.

PMID- 27043879
TI  - Challenges to Data Monitoring Committees When Regulatory Authorities Intervene.

PMID- 27043880
TI  - Selection of oxidant doses for in situ chemical oxidation of soils contaminated
      by polycyclic aromatic hydrocarbons (PAHs): A review.
AB  - In situ chemical oxidation (ISCO) is a promising alternative to thermal
      desorption for the remediation of soils contaminated with organic compounds such
      as polycyclic aromatic hydrocarbons (PAHs). For field application, one major
      issue is the selection of the optimal doses of the oxidizing solution, i.e. the
      oxidant and appropriate catalysts and/or additives. Despite an extensive
      scientific literature on ISCO, this choice is very difficult because many
      parameters differ from one study to another. The present review identifies the
      critical factors that must be taken into account to enable comparison of these
      various contributions. For example, spiked soils and aged, polluted soils cannot
      be compared; PAHs freshly spiked into a soil are fully available for degradation
      unlike a complex mixture of pollutants trapped in a soil for many years. Another
      notable example is the high diversity of oxidation conditions employed during
      batch experiments, although these affect the representativeness of the system.
      Finally, in this review a methodology is also proposed based on a combination of
      the stoichiometric oxidant demand of the organic pollutants and the design of
      experiments (DOE) in order to allow a better comparison of the various studies so
      far reported.

PMID- 27043881
TI  - Effect of renal function on whole blood and fibrin clot formation in atrial
      fibrillation patients on warfarin.
AB  - OBJECTIVE: Atrial fibrillation (AF) brings a risk of thrombosis, requiring oral
      coagulation, and is associated with renal impairment. The two processes may be
      linked, as altered fibrin clot structure is present in end-stage renal failure.
      We hypothesised that progressively deteriorating renal function is linked to
      altered whole blood and fibrin clot properties and fibrinolysis. METHODS:
      Thrombogenesis and fibrinolysis in 200 warfarinised AF patients was assessed by
      thromboelastography (TEG), a micro-plate assay (MPA) and the international
      normalized ratio (INR). Renal function was determined by creatinine clearance and
      two versions of the estimated glomerular filtration rate (eGFR). RESULTS: Two TEG
      indices independently reflecting thrombogenesis were linked to creatinine
      clearance (p < 0.01), whilst a third, reflecting clot strength, was linked to the
      eGFR (p < 0.001). MPA indices of thrombogenesis and clot density (p < 0.001), and
      an index of fibrinolysis (p < 0.001) were linked to the eGFR. The time for 50% of
      the fibrin clot to lyse was linked to creatinine clearance (p = 0.001). The INR
      was unrelated to any renal function index, and the CHA2DS2VASc score was
      unrelated to any index. CONCLUSION: In warfarinised AF patients, renal function
      is linked to whole blood clot and fibrin clot formation, structure and
      dissolution, but has no effect on the INR. Key messages Despite oral
      anticoagulation, patients with atrial fibrillation (AF) still suffer from stroke
      and venous thromboembolism. The effect of renal function in warfarinised patients
      with AF is unknown and may account for excess thrombosis and/or haemorrhage.
      Using two different laboratory methods, our data point to an effect of renal
      function on clot structure and function that is independent of an effect of
      warfarin.

PMID- 27043883
TI  - Outcomes in Adults With Acute Liver Failure Between 1998 and 2013: An
      Observational Cohort Study.
AB  - BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset
      hepatic dysfunction-without prior advanced liver disease-that is associated with
      high morbidity and mortality. Intensive care and liver transplantation provide
      support and rescue, respectively. OBJECTIVE: To determine whether changes in
      causes, disease severity, treatment, or 21-day outcomes have occurred in recent
      years among adult patients with ALF referred to U.S. tertiary care centers.
      DESIGN: Prospective observational cohort study. (ClinicalTrials .gov:
      NCT00518440). SETTING: 31 liver disease and transplant centers in the United
      States. PATIENTS: Consecutively enrolled patients-without prior advanced liver
      disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21
      day outcomes were compared over time annually for trends and were also stratified
      into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall
      clinical characteristics, disease severity, and distribution of causes remained
      similar throughout the study period. The 21-day survival rates increased between
      the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS],
      45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for
      each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma
      infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and
      vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N
      acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients
      with ALF not due to acetaminophen toxicity). When examined longitudinally,
      overall survival and TFS increased throughout the 16-year period. LIMITATIONS:
      The duration of enrollment, the number of patients enrolled, and possibly the
      approaches to care varied among participating sites. The results may not be
      generalizable beyond such specialized centers. CONCLUSION: Although
      characteristics and severity of ALF changed little over 16 years, overall
      survival and TFS improved significantly. The effects of specific changes in
      intensive care practice on survival warrant further study. PRIMARY FUNDING
      SOURCE: National Institutes of Health.

PMID- 27043882
TI  - Standardized benchmarking in the quest for orthologs.
AB  - Achieving high accuracy in orthology inference is essential for many comparative,
      evolutionary and functional genomic analyses, yet the true evolutionary history
      of genes is generally unknown and orthologs are used for very different
      applications across phyla, requiring different precision-recall trade-offs. As a
      result, it is difficult to assess the performance of orthology inference methods.
      Here, we present a community effort to establish standards and an automated web
      based service to facilitate orthology benchmarking. Using this service, we
      characterize 15 well-established inference methods and resources on a battery of
      20 different benchmarks. Standardized benchmarking provides a way for users to
      identify the most effective methods for the problem at hand, sets a minimum
      requirement for new tools and resources, and guides the development of more
      accurate orthology inference methods.

PMID- 27043884
TI  - Determinants and frequency of irritable bowel syndrome in a German sample.
AB  - BACKGROUND: To date there is no study that has estimated the prevalence of
      irritable bowel syndrome (IBS) in Germany according to the current Rome III
      criteria. The aim of the present study was to investigate the prevalence of IBS
      in a non-clinical German sample. Furthermore, we investigated the association of
      IBS with socio-demographic and psychological risk factors. METHODS: Baseline data
      from a prospective cohort study were analysed, including the IBS Module of the
      Rome III Diagnostic Questionnaires and validated psychometric scales including
      the Patient Health Questionnaire-15 (PHQ-15), the Big Five Inventory (BFI), the
      Perceived Stress Questionnaire (PSQ-5), and the Whiteley-Index (WI-7). The study
      population was compared to the German general population to appraise its
      representativeness. Multivariate logistic regression analyses were performed to
      identify possible risk factors associated with IBS. RESULTS: Between January 2011
      and September 2012, 2419 persons participated (female 54.0 %, mean age 37.4 +/-
      14.9 years). According to the Rome III criteria, 401 participants (16.6 %)
      suffered from IBS. Five predictors were independently associated with IBS:
      previous traveller's diarrhoea infection (OR = 1.76; 95 % CI = 1.34 to 2.31),
      higher somatic symptom burden (OR = 1.15; 95 % CI = 1.07 to 1.23), increased
      level of hypochondriasis (OR = 2.04; 95 % CI = 1.54 to 2.70), increased
      vulnerability to diarrhoea under stress (OR = 3.88; 95 % CI = 3.21 to 4.68) and
      perceived stress (OR = 1.43; 95 % CI = 1.04 to 1.99). CONCLUSIONS: Our analyses
      yielded a relatively high IBS prevalence estimate, compared to studies published
      more than ten years ago. This might partially be explained by the fact that the
      time criterion of the Rome III criteria (at least 3 days/month in last 3 months)
      is more inclusive compared to the time criterion of the Rome II criteria (at
      least 12 weeks, which need not be consecutive, in the preceding 12 months).

PMID- 27043885
TI  - Comorbidity in acute pancreatitis relates to organ failure but not to local
      complications.
AB  - OBJECTIVE: Organ failure and local complications contribute to morbidity and
      mortality in acute pancreatitis. Comorbidity is known to be related to organ
      failure. The impact of comorbidity on local complications has not yet been
      delineated. Moreover, it is not clear if the outcome of first-attacks and acute
      on-chronic episodes, respectively, differs from outcome in all episodes. METHODS:
      Consecutive cases of confirmed acute pancreatitis in a four-year period were
      reviewed. Charlson comorbidity index (CCI), complications (organ failure and
      local complications), disease severity (according to the revised Atlanta
      Classification), need for intensive care, and mortality were derived from the
      charts. RESULTS: A total of 391 episodes of acute pancreatitis were included.
      Patients with organ failure were significantly older (P< 0.001) und had a higher
      CCI (P< 0.001) than patients without organ failure. Patients with and without
      local complications did not significantly differ in age or CCI. The complication
      rate of the entire cohort (n = 391; 47.1 %) was comparable with the complication
      rate of first-attacks (n = 269; 46.8 %) and acute-on-chronic episodes (n = 68;
      47.1 %). The majority of the twelve deceased patients had been old and/or
      chronically ill. Six of these patients had an advanced malignant disease.
      CONCLUSIONS: Comorbidity and age clearly are contributors to organ failure and
      mortality. Local complications occur independently of age and concomitant
      diseases. The overall complication rate is not significantly influenced by
      preceding inflammation of the pancreas. To further improve care in patients with
      acute pancreatitis special attention should be given to old and multi-morbid
      patients.

PMID- 27043886
TI  - HBsAg and anti-HCV screening in elderly hospitalized patients of a German
      tertiary referral centre.
AB  - BACKGROUND: Elderly patients are under-represented in hepatitis B and C screening
      approaches, but may be at increased risk for advanced liver disease. We therefore
      screened a hospitalized elderly population. MATERIALS AND METHODS: 6011
      admissions to the department of internal medicine and neurology within one year
      were screened for HBsAg and anti-HCV (Elecsys((r))-HBsAg and -anti-HCV). Positive
      anti-HCV results were confirmed with the INNO-LIATM assay. HCV-RNA was analyzed
      by real-time PCR in the case of confirmed positive anti-HCV results, HBV-DNA in
      the confirmed HBsAg positive individuals. RESULTS: Patient's mean age (62.4
      years) was 19 years above that of the average German population. The confirmed
      HBsAg prevalence was 0.6 %. 34 % (n = 12/35) of HBsAg positive cases were newly
      diagnosed, three of them presented with HBV-DNA levels > 2000 IU/mL. The
      confirmed anti-HCV prevalence was 0.9 %. 14 % (n = 8/56) of anti-HCV positive
      patients were previously undiagnosed. HCV-RNA was positive in three of them. In
      newly diagnosed individuals cirrhosis was present in 1/12 of the HBsAg and in 3/8
      of the anti-HCV positive individuals. Compared to non-infected controls, the
      following risk factors were significantly more frequent in infected patients: (i)
      HBsAg: sexual exposure (20 % vs. 2 %), blood transfusion before 1992 (13 % vs. 6
      %), referrals from nursing homes (10 % vs. 1 %). (ii) Anti-HCV: blood transfusion
      before 1992 (41 % vs. 6 %), IVDU (25 % vs. 0.5 %), organ transplantation (20 %
      vs. 5 %), hemodialysis (11 % vs. 3 %). CONCLUSIONS: HBsAg and anti-HCV were
      underdiagnosed in a senescent population, however, only few cases presented with
      advanced liver disease. Referrals from nursing homes were at increased risk for
      HBV infection.

PMID- 27043887
TI  - [Extrapulmonary sarcoidosis: gastrointestinal involvement -case report and review
      of literature].
AB  - Sarcoidosis is a rare systemic disease characterized by noncaseating granulomas
      in affected organs. With > 90 % of all cases lung involvement is the most
      frequent site of manifestation of sarcoidosis, nevertheless multiple other organs
      can be affected. Extrapulmonary manifestations are lymph nodes, skin, nervous
      system, heart, eyes, bone marrow, spleen or gastrointestinal tract including
      liver and pancreas. Involvement of the gastrointestinal tract is rare, it can
      affect the whole intestine and is most frequently found in the stomach. Despite
      its infrequent manifestation, gastrointestinal sarcoidosis can have a significant
      clinical impact depending on the organ involved, so that early diagnosis is
      warranted. Medical treatment mainly consists of immunosuppressive therapy, most
      frequently with corticosteroids being the first treatment of choice. Dosage and
      duration of therapy is not well established yet. In the literature very limited
      data are available on this topic with randomized trials missing completely. The
      aim of this paper is to give a summary of the available data to this date. 

PMID- 27043888
TI  - Gastrointestinal stromal tumor as entry port for S. intermedius causing
      bacteremia and multiple liver abscesses. Case report and review of literature.
AB  - We report a case of a previously healthy 52-year-old man who presented with fever
      and liver lesions suspicious for metastatic disease, which proved subsequently to
      be abscesses. Further workup revealed a gastrointestinal stromal tumor (GIST) in
      the gastric corpus as entry port to Streptococcus intermedius-associated
      bacteremia and liver abscesses. After antibiotic treatment and surgical resection
      of the tumor, the patient recovered well. This unusual case indicates that
      gastrointestinal stromal tumors can remain undetected until they cause a life
      threatening infection. A review of recent literature pertaining to GIST and liver
      abscesses follows. 

PMID- 27043889
TI  - [Chronic diarrhea - diagnostic evaluation should always be done!].

PMID- 27043890
TI  - [Severe or not so severe acute pancreatitis: Does the first impression count?].

PMID- 27043891
TI  - Causes of Child and Youth Homelessness in Developed and Developing Countries: A
      Systematic Review and Meta-analysis.
AB  - IMPORTANCE: A systematic compilation of children and youth's reported reasons for
      street involvement is lacking. Without empirical data on these reasons, the
      policies developed or implemented to mitigate street involvement are not
      responsive to the needs of these children and youth. OBJECTIVE: To systematically
      analyze the self-reported reasons why children and youth around the world become
      street-involved and to analyze the available data by level of human development,
      geographic region, and sex. DATA SOURCES: Electronic searches of Scopus,
      PsychINFO, EMBASE, POPLINE, PubMed, ERIC, and the Social Sciences Citation Index
      were conducted from January 1, 1990, to the third week of July 2013. We searched
      the peer-reviewed literature for studies that reported quantitative reasons for
      street involvement. The following broad search strategy was used to search the
      databases: "street children" OR "street youth" OR "homeless youth" OR "homeless
      children" OR "runaway children" OR "runaway youth" or "homeless persons." STUDY
      SELECTION: Studies were included if they met the following inclusion criteria:
      (1) participants were 24 years of age or younger, (2) participants met our
      definition of street-connected children and youth, and (3) the quantitative
      reasons for street involvement were reported. We reviewed 318 full texts and
      identified 49 eligible studies. DATA EXTRACTION AND SYNTHESIS: Data were
      extracted by 2 independent reviewers. We fit logistic mixed-effects models to
      estimate the pooled prevalence of each reason and to estimate subgroup pooled
      prevalence by development level or geographic region. The meta-analysis was
      conducted from February to August 2015. MAIN OUTCOMES AND MEASURES: We created
      the following categories based on the reported reasons in the literature:
      poverty, abuse, family conflict, delinquency, psychosocial health, and other.
      RESULTS: In total, there were 13 559 participants from 24 countries, of which 21
      represented developing countries. The most commonly reported reason for street
      involvement was poverty, with a pooled-prevalence estimate of 39% (95% CI, 29%
      51%). Forty-seven studies included in this review reported family conflict as the
      reason for street involvement, with a pooled prevalence of 32% (95% CI, 26%-39%).
      Abuse was equally reported in developing and developed countries as the reason
      for street involvement, with a pooled prevalence of 26% (95% CI, 18%-35%).
      Delinquency was the least frequently cited reason overall, with a pooled
      prevalence of 10% (95% CI, 5%-20%). CONCLUSIONS AND RELEVANCE: The street
      connected children and youth who provided reasons for their street involvement
      infrequently identified delinquent behaviors for their circumstances and
      highlighted the role of poverty as a driving factor. They require support and
      protection, and governments globally are called on to reduce the socioeconomic
      inequities that cause children and youth to turn to the streets in the first
      place, in all regions of the world.

PMID- 27043892
TI  - Response to Letter to the Editor Regarding OpT2mise Study.

PMID- 27043893
TI  - Parsing the Utility of CT and MRI in the Subaxial Cervical Spine Injury
      Classification (SLIC) System: Is CT SLIC Enough?
AB  - OBJECTIVE: The aim of our blinded retrospective study was to evaluate the
      diagnostic performance of the Subaxial Cervical Spine Injury Classification
      (SLIC) System in predicting the need for surgical intervention after subaxial
      cervical spine injury; SLIC scores were determined using CT alone or both CT and
      MRI. MATERIALS AND METHODS: Patients were included if they had injuries that were
      subaxial (C3-C7), if they had undergone CT and MRI within 48 hours of admission,
      if they were either treated surgically or had sufficient clinical documentation
      describing nonsurgical management (halo device or hard collar), and if the SLIC
      neurologic score could be determined from a documented neurologic examination.
      Two hundred two consecutive patients (139 surgical patients and 63 nonsurgical
      control subjects) from January 2010 through December 2013 met all criteria and
      were included in the study. Additionally, 40 patients were randomly selected from
      this group for the purpose of determining interrater agreement. Initially,
      readers gave a SLIC score (< 4 for nonsurgical, 4 = indeterminate, > 4 for
      surgical) based on neurologic status and CT only. After waiting 4 weeks to
      minimize recall bias, the readers repeated scoring with the addition of MRI.
      Diagnostic performance values-that is, sensitivity, specificity, AUC under the
      ROC curve, and interrater agreement (Cohen kappa)-for both trials were
      determined. RESULTS: Using a SLIC score of 4 as the cutoff value for surgical
      intervention, we found that SLIC scoring based on CT and MRI had a sensitivity of
      94.6%, specificity of 71.0%, and AUC of 0.87 with a kappa value of 0.28. SLIC
      scoring based on CT alone had a sensitivity of 86.2%, specificity of 77.3%, and
      AUC of 0.88 with a kappa value of 0.52. CONCLUSION: SLIC scoring based on CT
      alone performs similarly to SLIC scoring based on CT and MRI but with improved
      interobserver agreement. Although MRI is useful for surgical planning, these
      results indicate that MRI may have limited added value in the initial triage of
      patients with subaxial cervical spine injury for conservative versus surgical
      management.

PMID- 27043894
TI  - An artificial photosynthetic model based on a molecular triad of boron
      dipyrromethene and phthalocyanine.
AB  - A boron dipyrromethene (BDP) unit and its monostyryl derivative (MSBDP) were
      introduced at the axial positions of a silicon(iv) phthalocyanine (SiPc) core.
      The absorption spectrum of this compound virtually covered the entire visible
      region (300-700 nm) and could be interpreted as a superposition of the spectra of
      individual components. The intramolecular photoinduced energy and charge transfer
      processes of this triad were studied using steady-state and time-resolved
      spectroscopic methods in polar and nonpolar solvents. Upon BDP-part excitation, a
      fast and highly efficient excitation energy transfer (EET) occurred resulting in
      strong quenching of its fluorescence and the formation of the first excited
      singlet state of SiPc or MSBDP. It was found that both EET and charge transfer
      (CT) processes competed with each other in the depopulation of the first excited
      singlet state of the MSBDP moiety. The former strongly superseded CT in nonpolar
      toluene, whereas the latter was dominant in a polar environment. Direct or
      indirect (via EET) excitation of the SiPc-part of the triad was followed by CT
      yielding the charge-separated (CS) species BDP-SiPc(-)-MSBDP(+). The energy gap
      between the CS state and the S1-state of the SiPc moiety was found to be only
      0.06 eV in toluene, which facilitated the back CT process and resulted in the
      appearance of thermally activated delayed fluorescence. With increasing solvent
      polarity, the energy of the CS state reduced resulting in the disappearance of
      the delayed fluorescence in CHCl3, tetrahydrofuran or N,N-dimethylformamide. The
      charge recombination rate, k(CR), was very fast in polar DMF (3.3 * 10(10) s(
      1)), whereas this process was two-orders of magnitude slower in nonpolar toluene
      (k(CR) = 4.0 * 10(8) s(-1)).

PMID- 27043895
TI  - Systematic Study of Inherent Antibacterial Properties of Magnesium-based
      Biomaterials.
AB  - Magnesium-based materials are preferred in temporary orthopedic implants because
      of their biodegradability, mechanical properties, and intrinsic antibacterial
      properties. However, the fundamental mechanism of bacteria killing and roles of
      various factors are not clearly understood. In this study, we performed a
      systematic study of the antibacterial properties of two common Mg-based materials
      using a biofilm forming bacterium. Complete annihilation of the initial 3 * 10(4)
      bacteria is achieved with both materials in 0.1 mL LB medium in 24 h, whereas in
      the control, they proliferate to 10(10). The bacteria are killed more effectively
      in the solution than on the surface, and the bacteria killing efficiency depends
      more on the concentrations of the magnesium ions and hydroxyl ions than the
      corrosion rate. The killing process is reproduced using formula solutions, and
      killing is revealed to stem from the synergetic effects of alkalinity and
      magnesium ions instead of either one of them or Mg(OH)2 precipitate. Reactive
      oxygen species (ROS) are detected from the bacteria during the killing process
      but are not likely produced by the redox reaction directly, because they are
      detected at least 3 h after the reaction has commenced. The average cell size
      increases during the killing process, suggesting that the bacteria have
      difficulty with normal division which also contributes to the reduced bacteria
      population. 

PMID- 27043896
TI  - Violence in Mexico: A social or public health problem?
AB  - This article seeks to explain the importance of violence as a social phenomenon
      and public health, trying to envision this issue not only from a curative
      approach to health, but from the social determinants of health, such as
      economics, politics and the administration of justice. Here, the younger
      population lacks real opportunities with an ?absent State? that fails to provide
      structure. These frameworks play a fundamental role in the manifestation of
      violence. Thus, the debate for addressing and resolving violence opens the way to
      new perspectives regarding social factors as part of a public health, which
      cannot be oblivious to the state of the collective. Thus, the analysis of this
      situation shows that we cannot keep overlooking the whole picture of the real
      problem in the social health of our world instead of focusing on its discordant
      parts. 

PMID- 27043897
TI  - Hyperoxia Is Associated With Poor Outcomes in Pediatric Cardiac Patients
      Supported on Venoarterial Extracorporeal Membrane Oxygenation.
AB  - OBJECTIVES: Patients who require venoarterial extracorporeal membrane oxygenation
      because of cardiac failure frequently have supranormal blood oxygen tensions
      (hyperoxia). Recent studies have suggested worse outcomes in patients with
      hyperoxia after resuscitation from cardiac or respiratory arrests, presumably
      because of oxidative stress. There are limited data regarding the effect of
      hyperoxia on outcomes in pediatric patients on venoarterial extracorporeal
      membrane oxygenation. DESIGN: Retrospective chart review. SETTING: Pediatric
      cardiothoracic ICU. PATIENTS: Cardiac surgery patients less than 1 year old
      requiring venoarterial extracorporeal membrane oxygenation in the postoperative
      period from 2007 to 2013. MEASUREMENTS AND MAIN RESULTS: In 93 infants (median
      time on extracorporeal membrane oxygenation, 5 d), mortality at 30 days post
      surgery (primary outcome) was 38%. Using a receiver operating characteristic
      curve, a mean PaO2 of 193 mm Hg in the first 48 hours of extracorporeal membrane
      oxygenation was determined to have good discriminatory ability with regard to 30
      day mortality. Univariate analysis identified a mean PaO2 greater than 193 mm Hg
      (p = 0.001), longer cardiopulmonary bypass times (p = 0.09), longer duration of
      extracorporeal membrane oxygenation (p < 0.0001), and higher extracorporeal
      membrane oxygenation pump flows (p = 0.052) as possible risk factors for 30-day
      mortality. In multivariable analysis controlling for the variables listed above,
      a mean PaO2 greater than 193 mm Hg remained an independent risk factor for
      mortality (p = 0.03). In addition, a mean PaO2 greater than 193 mm Hg was
      associated with the need for renal dialysis (p = 0.02) but not with neurologic
      injury (p = 0.41) during the hospitalization. CONCLUSIONS: In infants with
      congenital heart disease who are placed on venoarterial extracorporeal membrane
      oxygenation postoperatively, hyperoxia (defined as a mean PaO2 > 193 mm Hg in the
      first 48 hr of extracorporeal membrane oxygenation) was an independent risk
      factor for 30-day mortality after surgery. Future studies are needed to delineate
      the causative or associative role of hyperoxia with outcomes, especially in
      children with baseline cyanosis who may be more susceptible to the effects of
      oxidative stress.

PMID- 27043898
TI  - Does the Site of Sampling and Type of Diagnostic Test for Viruses Matter in
      Suspected Acute Severe Viral Respiratory Infection?

PMID- 27043899
TI  - Ventilator-Associated Respiratory Infections: Choosing Between Scylla and
      Charybdis.

PMID- 27043900
TI  - The Focus of Treating Pediatric Acute Hypoxemic Respiratory Failure in
      Immunocompromised Patients.

PMID- 27043901
TI  - Understanding the Resuscitation of Children With a Single Ventricle, We Are
      Looking at the Tip of an Iceberg.

PMID- 27043902
TI  - Water, Water, Everywhere...Fluid Overload in the Postoperative Cardiac Patient:
      Marker of Severity or True Cause of Morbidity and Mortality?

PMID- 27043903
TI  - Sedation Practices in Pediatric Cardiac ICUs After Cardiopulmonary Bypass.

PMID- 27043904
TI  - Oxygen: A Luxurious Life-Giving and Potentially Toxic Gas.

PMID- 27043905
TI  - "In Through the Out Door": Led Zeppelin and Drug Administration in Continuous
      Renal Replacement Therapy.

PMID- 27043906
TI  - Observed Trauma in the PICU and Parental Meaning Making.

PMID- 27043907
TI  - Neonatal Acute Kidney Injury: The Signal Is Clear. It Is Time to Move the Field
      Forward.

PMID- 27043908
TI  - Rest and Regeneration for the Injured Lung.

PMID- 27043909
TI  - Kosher Propensity Matching.

PMID- 27043910
TI  - The authors reply.

PMID- 27043911
TI  - PICU-Acquired Weakness: Underestimated and Underreported.

PMID- 27043912
TI  - Evaluation of a Resident-Led Project to Decrease Phlebotomy Rates in the
      Hospital: Think Twice, Stick Once.

PMID- 27043913
TI  - Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data.
AB  - Humans move frequently and tend to carry parasites among areas with endemic
      malaria and into areas where local transmission is unsustainable. Human-mediated
      parasite mobility can thus sustain parasite populations in areas where they would
      otherwise be absent. Data describing human mobility and malaria epidemiology can
      help classify landscapes into parasite demographic sources and sinks, ecological
      concepts that have parallels in malaria control discussions of transmission foci.
      By linking transmission to parasite flow, it is possible to stratify landscapes
      for malaria control and elimination, as sources are disproportionately important
      to the regional persistence of malaria parasites. Here, we identify putative
      malaria sources and sinks for pre-elimination Namibia using malaria parasite rate
      (PR) maps and call data records from mobile phones, using a steady-state analysis
      of a malaria transmission model to infer where infections most likely occurred.
      We also examined how the landscape of transmission and burden changed from the
      pre-elimination setting by comparing the location and extent of predicted pre
      elimination transmission foci with modeled incidence for 2009. This comparison
      suggests that while transmission was spatially focal pre-elimination, the spatial
      distribution of cases changed as burden declined. The changing spatial
      distribution of burden could be due to importation, with cases focused around
      importation hotspots, or due to heterogeneous application of elimination effort.
      While this framework is an important step towards understanding progressive
      changes in malaria distribution and the role of subnational transmission dynamics
      in a policy-relevant way, future work should account for international parasite
      movement, utilize real time surveillance data, and relax the steady state
      assumption required by the presented model. 

PMID- 27043914
TI  - In silico screening of molecular imprinting prepolymerization systems:
      oseltamivir selective polymers through full-system molecular dynamics-based
      studies.
AB  - All-component molecular dynamics studies were used to probe a library of
      oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers
      included one of five functional monomers (acrylamide, hydroxyethylmethacrylate,
      methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of
      three porogens (acetonitrile, chloroform, methanol) combined with the
      crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2
      methylpropionitrile). Polymers were characterized by nitrogen gas sorption
      measurements and SEM, and affinity studies performed using radioligand binding in
      various media. In agreement with the predictions made from the simulations,
      polymers prepared in acetonitrile using either methacrylic or
      trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir.
      Further, the ensemble of interactions observed in the methanol system provided an
      explanation for the morphology of polymers prepared in this solvent. The
      materials developed here offer potential for use in solid-phase extraction or for
      catalysis. The results illustrate the strength of this in silico strategy as a
      potential prognostic tool in molecularly imprinted polymer design. 

PMID- 27043915
TI  - Re- and Demineralization Characteristics of Enamel Depending on Baseline Mineral
      Loss and Lesion Depth in situ.
AB  - OBJECTIVES: The aim of this double-blinded, randomized, cross-over in situ study
      was to evaluate the re- and demineralization characteristics of sound enamel as
      well as lowly and highly demineralized caries-like enamel lesions after the
      application of different fluoride compounds. METHODS: In each of three
      experimental legs of 4 weeks, 21 participants wore intraoral mandibular
      appliances containing 4 bovine enamel specimens (2 lowly and 2 highly
      demineralized). Each specimen included one sound enamel and either one lowly
      demineralized (7 days, pH 4.95) or one highly demineralized (21 days, pH 4.95)
      lesion, and was positioned 1 mm below the acrylic under a plastic mesh. The three
      randomly allocated treatments (application only) included the following
      dentifrices: (1) 1,100 ppm F as NaF, (2) 1,100 ppm F as SnF2 and (3) 0 ppm F
      (fluoride-free) as negative control. Differences in integrated mineral loss
      (x0394;x0394;Z) and lesion depth (x0394;LD) were calculated between values before
      and after the in situ period using transversal microradiography. RESULTS: Of the
      21 participants, 6 did not complete the study and 2 were excluded due to protocol
      violation. Irrespectively of the treatment, higher baseline mineral loss and
      lesion depth led to a less pronounced change in mineral loss and lesion depth.
      Except for x0394;x0394;Z of the dentifrice with 0 ppm F, sound surfaces showed
      significantly higher x0394;x0394;Z and x0394;LD values compared with lowly and
      highly demineralized lesions (p < 0.05, t test). CONCLUSION: Re- and
      demineralization characteristics of enamel depended directly on baseline mineral
      loss and lesion depth. Treatment groups should therefore be well balanced with
      respect to baseline mineral loss and lesion depth.

PMID- 27043916
TI  - Targeting coagulation factor XII as a novel therapeutic option in brain trauma.
AB  - OBJECTIVE: Traumatic brain injury is a major global public health problem for
      which specific therapeutic interventions are lacking. There is, therefore, a
      pressing need to identify innovative pathomechanism-based effective therapies for
      this condition. Thrombus formation in the cerebral microcirculation has been
      proposed to contribute to secondary brain damage by causing pericontusional
      ischemia, but previous studies have failed to harness this finding for
      therapeutic use. The aim of this study was to obtain preclinical evidence
      supporting the hypothesis that targeting factor XII prevents thrombus formation
      and has a beneficial effect on outcome after traumatic brain injury. METHODS: We
      investigated the impact of genetic deficiency of factor XII and acute inhibition
      of activated factor XII with a single bolus injection of recombinant human
      albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular
      thrombus formation and the subsequent outcome in 2 mouse models of traumatic
      brain injury. RESULTS: Our study showed that both genetic deficiency of factor
      XII and an inhibition of activated factor XII in mice minimize trauma-induced
      microvascular thrombus formation and improve outcome, as reflected by better
      motor function, reduced brain lesion volume, and diminished neurodegeneration.
      Administration of human factor XII in factor XII-deficient mice fully restored
      injury-induced microvascular thrombus formation and brain damage. INTERPRETATION:
      The robust protective effect of rHA-Infestin-4 points to a novel treatment option
      that can decrease ischemic injury after traumatic brain injury without increasing
      bleeding tendencies. Ann Neurol 2016;79:970-982.

PMID- 27043917
TI  - What drives the association between weight-conscious peer groups and disordered
      eating? Disentangling genetic and environmental selection from pure socialization
      effects.
AB  - Previous studies suggest strong associations between exposure to weight-conscious
      peer groups and increased levels of disordered eating. This association has been
      attributed to socialization effects (i.e., membership leads to disordered
      eating); however, selection effects (i.e., selecting into peer groups based on
      genetic and/or environmental predispositions toward disordered eating) could
      contribute to or even account for these associations. The current study was the
      first to use a co-twin control design to disentangle these types of selection
      factors from socialization effects. Participants included 610 female twins (ages
      8-14) drawn from the Michigan State University Twin Registry. To comprehensively
      examine a range of eating pathology, several disordered eating attitudes and
      behaviors (e.g., body dissatisfaction, binge eating) were examined via self
      report questionnaires. Questionnaires also were used to assess peer group
      emphasis on body weight and shape. Replicating previous results, significant
      individual-level associations were found between membership in weight-conscious
      peer groups and disordered eating. However, co-twin control analyses indicated
      that these associations were largely due to genetic and/or shared environmental
      selection factors rather than pure socialization effects. Importantly, results
      remained unchanged when controlling for pubertal status, suggesting that effects
      do not vary across developmental stage. Overall, these findings question whether
      associations between weight-conscious peer groups and disordered eating are due
      entirely to socialization processes. Future studies are needed to identify the
      specific genetic and/or shared environmental factors that may drive selection
      into weight-conscious peer groups.

PMID- 27043918
TI  - Superior orientation discrimination and increased peak gamma frequency in autism
      spectrum conditions.
AB  - While perception is recognized as being atypical in individuals with autism
      spectrum conditions (ASC), the underlying mechanisms for such atypicality are
      unclear. Here we test the hypothesis that individuals with ASC will show enhanced
      orientation discrimination compared with neurotypical observers. This prediction
      is based both on anecdotal report of superior discriminatory skills in ASC and
      also on evidence in the auditory domain that some individuals with ASC have
      superior pitch discrimination. In order to establish whether atypical perception
      might be mediated by an imbalance in the ratio of neural excitation and
      inhibition (E:I ratio), we also measured peak gamma frequency, which provides an
      indication of neural inhibition levels. Using a rigorous thresholding method, we
      found that orientation discrimination thresholds for obliquely oriented stimuli
      were significantly lower in participants with ASC. Using EEG to measure the
      visually induced gamma band response, we also found that peak gamma frequency was
      higher in participants with ASC, relative to a well-matched control group. These
      novel results suggest that neural inhibition may be increased in the occipital
      cortex of individuals with ASC. Implications for existing theories of an
      imbalance in the E:I ratio of ASC are discussed.

PMID- 27043919
TI  - Shear Assisted Electrochemical Exfoliation of Graphite to Graphene.
AB  - The exfoliation characteristics of graphite as a function of applied anodic
      potential (1-10 V) in combination with shear field (400-74 400 s(-1)) have been
      studied in a custom-designed microfluidic reactor. Systematic investigation by
      atomic force microscopy (AFM) indicates that at higher potentials thicker and
      more fragmented graphene sheets are obtained, while at potentials as low as 1 V,
      pronounced exfoliation is triggered by the influence of shear. The shear-assisted
      electrochemical exfoliation process yields large (~10 MUm) graphene flakes with a
      high proportion of single, bilayer, and trilayer graphene and small ID/IG ratio
      (0.21-0.32) with only a small contribution from carbon-oxygen species as
      demonstrated by X-ray photoelectron spectroscopy measurements. This method
      comprises intercalation of sulfate ions followed by exfoliation using shear
      induced by a flowing electrolyte. Our findings on the crucial role of
      hydrodynamics in accentuating the exfoliation efficiency suggest a safer,
      greener, and more automated method for production of high quality graphene from
      graphite. 

PMID- 27043920
TI  - Inhibitory effect of baicalin on allergic response in ovalbumin-induced allergic
      rhinitis guinea pigs and lipopolysaccharide-stimulated human mast cells.
AB  - OBJECTIVE: Baicalin, a flavonoid compound purified from the dry roots of
      Scutellaria baicalensis Georgi, has generally been used for the treatment of
      various allergic diseases. However, there is little information about the anti
      inflammatory effects of baicalin for allergic rhinitis. This study aims to
      investigate the anti-allergic effect of baicalin on allergic response in
      ovalbumin (OVA)-induced allergic rhinitis guinea pigs and lipopolysaccharide
      (LPS)-stimulated human mast cells. METHODS: Using in vivo models, we evaluated
      the effect of baicalin on allergic rhinitis symptoms via recording the number of
      nasal rubs and sneezes. The levels of histamine, OVA-specific immunoglobulin
      E(IgE), eosinophil cationic protein (ECP) and inflammatory cytokines were
      measured using enzyme-linked immunosorbent assay (ELISA). The histological
      changes of nasal mucosa were observed by light microscope after HE staining. In
      vitro, the release of histamine and beta-hexosaminidase of compound 48/80-induced
      human mast cells were measured by ELISA and PNP-NAG colorimetry, respectively.
      The productions of inflammatory cytokines of LPS-stimulated human mast cells were
      determined using ELISA. Western blot was used to test the protein expression of
      JAK2, p-JAK2, STAT5, p-STAT5, IKKbeta, p-IKKbeta, IkappaBalpha, p-IkappaBalpha
      and NF-kappaB (p65) of LPS-stimulated human mast cells. RESULTS: The oral
      administration of baicalin at doses of 50 and 200 mg/kg improved allergic
      rhinitis symptoms and the histological changes of nasal mucosa and decreased the
      serum levels of histamine, ECP, interleukin (IL)-1beta, IL-6, IL-8, tumor
      necrosis factor (TNF)-alpha and OVA-specific IgE in OVA-induced allergic rhinitis
      guinea pigs. In vitro, baicalin suppressed the release of histamine and beta
      hexosaminidase in compound 48/80-induced human mast cells. In addition, baicalin
      also inhibited the productions of inflammatory cytokines such as IL-1beta, IL-6,
      IL-8 and TNF-alpha and suppressed the phosphorylation of JAK2, STAT5, IKKbeta,
      IkappaBalpha and the nuclear translocation of NF-kappaB (p65) subunit in LPS
      stimulated human mast cells. CONCLUSIONS: These results suggest that baicalin can
      effectively prevent allergic response in OVA-induced allergic rhinitis guinea
      pigs and inhibit inflammatory response via blocking JAK2-STAT5 and NF-kappaB
      signaling pathways in LPS-stimulated human mast cells. Considered together,the
      results show that baicalin may be a useful drug in the treatment of allergic
      rhinitis.

PMID- 27043921
TI  - Real-Time Imaging of the Formation of Au-Ag Core-Shell Nanoparticles.
AB  - We study the overgrowth process of silver-on-gold nanocubes in dilute, aqueous
      silver nitrate solution in the presence of a reducing agent, ascorbic acid, using
      in situ liquid-cell electron microscopy. Au-Ag core-shell nanostructures were
      formed via two mechanistic pathways: (1) nuclei coalescence, where the Ag
      nanoparticles absorbed onto the Au nanocubes, and (2) monomer attachment, where
      the Ag atoms epitaxially deposited onto the Au nanocubes. Both pathways lead to
      the same Au-Ag core-shell nanostructures. Analysis of the Ag deposition rate
      reveals the growth modes of this process and shows that this reaction is
      chemically mediated by the reducing agent.

PMID- 27043922
TI  - Thirty Gigahertz Optoelectronic Mixing in Chemical Vapor Deposited Graphene.
AB  - The remarkable properties of graphene, such as broadband optical absorption, high
      carrier mobility, and short photogenerated carrier lifetime, are particularly
      attractive for high-frequency optoelectronic devices operating at 1.55 MUm
      telecom wavelength. Moreover, the possibility to transfer graphene on a silicon
      substrate using a complementary metal-oxide-semiconductor-compatible process
      opens the ability to integrate electronics and optics on a single cost-effective
      chip. Here, we report an optoelectronic mixer based on chemical vapor-deposited
      graphene transferred on an oxidized silicon substrate. Our device consists in a
      coplanar waveguide that integrates a graphene channel, passivated with an atomic
      layer-deposited Al2O3 film. With this new structure, 30 GHz optoelectronic mixing
      in commercially available graphene is demonstrated for the first time. In
      particular, using a 30 GHz intensity-modulated optical signal and a 29.9 GHz
      electrical signal, we show frequency downconversion to 100 MHz. These results
      open promising perspectives in the domain of optoelectronics for radar and radio
      communication systems.

PMID- 27043923
TI  - Vibrational spectroscopy in sensing radiobiological effects: analyses of targeted
      and non-targeted effects in human keratinocytes.
AB  - Modern models of radiobiological effects include mechanisms of damage initiation,
      sensing and repair, for those cells that directly absorb ionizing radiation as
      well as those that experience molecular signals from directly irradiated cells.
      In the former case, the effects are termed targeted effects while, in the latter,
      non-targeted effects. It has emerged that phenomena occur at low doses below 1 Gy
      in directly irradiated cells that are associated with cell-cycle-dependent
      mechanisms of DNA damage sensing and repair. Likewise in non-targeted bystander
      irradiated cells the effect saturates at 0.5 Gy. Both effects at these doses
      challenge the limits of detection of vibrational spectroscopy. In this paper, a
      study of the sensing of both targeted and non-targeted effects in HaCaT human
      keratinocytes irradiated with gamma ray photons is conducted with vibrational
      spectroscopy. In the case of directly irradiated cells, it is shown that the
      HaCaT cell line does exhibit both hyperradiosensitivity and increased
      radioresistance at low doses, a transition between the two effects occurring at a
      dose of 200 mGy, and that cell survival and other physiological effects as a
      function of dose follow the induced repair model. Both Raman and FTIR signatures
      are shown to follow a similar model, suggesting that the spectra include
      signatures of DNA damage sensing and repair. In bystander-irradiated cells, pro-
      and anti-apoptotic signalling and mechanisms of ROS damage were inhibited in the
      mitogen-activated protein kinase (MAPK) transduction pathway. It is shown that
      Raman spectral profiles of bystander-irradiated cells are correlated with markers
      of bystander signalling and molecular transduction. This work demonstrates for
      the first time that both targeted and non-targeted effects of ionizing radiation
      damage are detected by vibrational spectroscopy in vitro.

PMID- 27043924
TI  - How Multidisciplinary Are the Multidisciplinary Journals Science and Nature?
AB  - Interest in cross-disciplinary research knowledge interchange runs high. Review
      processes at funding agencies, such as the U.S. National Science Foundation,
      consider plans to disseminate research across disciplinary bounds. Publication in
      the leading multidisciplinary journals, Nature and Science, may signify the
      epitome of successful interdisciplinary integration of research knowledge and
      cross-disciplinary dissemination of findings. But how interdisciplinary are they?
      The journals are multidisciplinary, but do the individual articles themselves
      draw upon multiple fields of knowledge and does their influence span disciplines?
      This research compares articles in three fields (Cell Biology, Physical
      Chemistry, and Cognitive Science) published in a leading disciplinary journal in
      each field to those published in Nature and Science. We find comparable degrees
      of interdisciplinary integration and only modest differences in cross
      disciplinary diffusion. That said, though the rate of out-of-field diffusion
      might be comparable, the sheer reach of Nature and Science, indicated by their
      potent Journal Impact Factors, means that the diffusion of knowledge therein can
      far exceed that of leading disciplinary journals in some fields (such as Physical
      Chemistry and Cognitive Science in our samples). 

PMID- 27043925
TI  - The role of infarct transmural extent in infarct extension: A computational
      study.
AB  - Infarct extension, a process involving progressive extension of the infarct zone
      (IZ) into the normally perfused border zone (BZ), leads to continuous degradation
      of the myocardial function and adverse remodelling. Despite carrying a high risk
      of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and
      infarct extension remains unexplored. In the present study, we developed a 3D
      truncated ellipsoidal left ventricular model incorporating realistic
      electromechanical properties and fibre orientation to examine the mechanical
      interaction among the remote, infarct and BZs in the presence of varying infarct
      transmural extent (TME). Localized highly abnormal systolic fibre stress was
      observed at the BZ, owing to the simultaneous presence of moderately increased
      stiffness and fibre strain at this region, caused by the mechanical tethering
      effect imposed by the overstretched IZ. Our simulations also demonstrated the
      greatest tethering effect and stress in BZ regions with fibre direction
      tangential to the BZ-remote zone boundary. This can be explained by the lower
      stiffness in the cross-fibre direction, which gave rise to a greater stretching
      of the IZ in this direction. The average fibre strain of the IZ, as well as the
      maximum stress in the sub-endocardial layer, increased steeply from 10% to 50%
      infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we
      found impairment in the myocardial energy efficiency and elevated energy
      expenditure with increasing infarct TME, which we believe to place the BZ at
      further risk of hypoxia. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27043926
TI  - Alcoholic relapse damages liver allografts.

PMID- 27043927
TI  - Prognostic value of midtreatment FDG-PET in oropharyngeal cancer.
AB  - BACKGROUND: Prognostic metabolic imaging indices are needed for risk
      stratification for patients with locally advanced oropharyngeal cancer. METHODS:
      We retrospectively examined pretreatment and midtreatment fluorodeoxyglucose
      positron emission tomography (FDG-PET) parameters in patients with locally
      advanced oropharyngeal cancer who were treated with definitive chemoradiation.
      RESULTS: A total of 74 patients were evaluated. Pretreatment metabolic tumor
      volume (MTV) using threshold of 50% standardized uptake value (SUV) maximum
      (MTV50% ) was associated with progression-free survival (PFS; p = .003; hazard
      ratio [HR] = 1.57 per 10 cc; 95% confidence interval [CI] = 1.17-2.11) and
      overall survival (OS; p = .01; HR = 1.36 per 10 cc; 95% CI = 1.07-1.74).
      Midtreatment MTV using a threshold of SUV 2.0 (MTV2.0 ) was associated with PFS
      (p < .001; HR = 1.24 per 10 cc; 95% CI = 1.10-1.39) and OS (p = .009; HR = 1.21
      per 10 cc; 95% CI = 1.05-1.39). Nodal total lesion glycolysis (TLG) velocity >5%
      decrease/week was associated with improved PFS (p = .04; HR = 0.37; 95% CI = 0.15
      0.95). CONCLUSION: Metabolic response during chemoradiation is associated with
      survival in locally advanced oropharyngeal cancer and may aid with risk-adapting
      treatment. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: First-1478, 2016.

PMID- 27043928
TI  - Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese
      Patients.
AB  - BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is
      increasing rapidly. Many authors feel that this increase is due to over-diagnosis
      and that one of the contributing factors is the increasing use of various imaging
      studies. The rate of obesity has also been increasing in the United States. It
      has been suggested that patients with an increased body mass index (BMI kg/m2)
      have a higher incidence of WDTC than patients with normal BMI. One might
      hypothesize that thyroid nodules are more difficult to palpate in obese patients
      and that as more cancers are detected by imaging the apparent rate of increase in
      WDTC in obese patients would appear to be greater than in non-obese patients.
      This study was undertaken to evaluate this hypothesis by determining if there is
      any difference in the way thyroid cancers are initially detected in obese and non
      obese patients. METHODS: The medical records of all 519 patients with a
      postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone
      Medical Center from January 1, 2007 through August 31, 2010 by the three members
      of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non
      obese (BMI<30 kg/m2) and Obese (BMI>=30 kg/m2) groups. Patients were also divided
      by the initial method of detection of their tumor into Palpation, Imaging, and
      Incidental groups. RESULTS: The final study group contained 270 patients,
      181(67%) of whom were in the Non-obese Group and 89(33%) were in the Obese Group.
      In the Non-obese group, 81(45%) of tumors were found by palpation, 72(40%) were
      found by imaging, and 28(16%) were found incidentally. In the Obese group,
      40(45%) were found by palpation, 38(43%) were found by imaging, and 11(12%) were
      found incidentally. These differences were not statistically significant (p-value
      0.769). CONCLUSION: We show that BMI does not play a role in the method of
      initial detection in patients with WDTC. This suggests that the prevalence of
      WDTC detected by imaging is not an artifact caused by an increasingly obese
      population and that any association of WDTC and obesity is not related to the way
      in which these tumors are detected.

PMID- 27043929
TI  - Effects of Pyrolysis Temperature on Product Yields and Energy Recovery from Co
      Feeding of Cotton Gin Trash, Cow Manure, and Microalgae: A Simulation Study.
AB  - The intensive search of new and cleaner energy catches interest in recent years
      due to huge consumption of fossil fuels coupled with the challenge of energy and
      environmental sustainability. Production of renewable and environmentally benign
      energy from locally available raw materials is coming in the frontline. In this
      work, conversion of the combined biomass (cotton gin trash, cow manure, and
      Microalgae [Nannochloropsis oculata]) through batch pyrolysis has been
      investigated. The effect of temperature to the production of energy fuels such as
      bio-oil, char, and biogas have been simulated considering the yield and energy
      content as responses. Result of the investigation generally revealed that the
      proportions of the different biomass did not significantly affect the product
      yield and energy recovery. Significant effect of temperature is evident in the
      simulation result of energy recovery whereby maximum conversion was achieved at
      400 degrees C for char (91 wt%), 600 degrees C for syngas (22 wt%), and 551
      degrees C for bio-oil (48 wt%). Overall energy conversion efficiency of 75.5% was
      obtained at 589 degrees C in which 15.6 MJ/kg of mixed biomass will be elevated
      to pyrolysis products. 

PMID- 27043930
TI  - Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing:
      Subjective Experience, Motor Responsiveness and Catastrophizing.
AB  - Although serotonin is known to play an important role in pain processing, the
      relationship between the polymorphism in 5-HTTLPR and pain processing is not well
      understood. To examine the relationship more comprehensively, various factors of
      pain processing having putative associations with 5-HT functioning were studied,
      namely the subjective pain experience (pain threshold, rating of experimental
      pain), catastrophizing about pain (Pain Catastrophizing Scale = PCS) and motor
      responsiveness (facial expression of pain). In 60 female and 67 male
      participants, heat pain stimuli were applied by a contact thermode to assess pain
      thresholds, supra-threshold ratings and a composite score of pain-relevant facial
      responses. Participants also completed the PCS and were grouped based on their 5
      HTTLPR genotype (bi-allelic evaluation) into a group with s-allele carriers (ss,
      sl) and a second group without (ll). S-allele carriers proved to have lower pain
      thresholds and higher PCS scores. These two positive findings were unrelated to
      each other. No other difference between genotype groups became significant. In
      all analyses, "age" and "gender" were controlled for. In s-allele carriers the
      subjective pain experience and the tendency to catastrophize about pain was
      enhanced, suggesting that the s-allele might be a risk factor for the development
      and maintenance of pain. This risk factor seems to act via two independent
      routes, namely via the sensory processes of subjective pain experiences and via
      the booster effects of pain catastrophizing. 

PMID- 27043931
TI  - Optimizing Real-Time Vaccine Allocation in a Stochastic SIR Model.
AB  - Real-time vaccination following an outbreak can effectively mitigate the damage
      caused by an infectious disease. However, in many cases, available resources are
      insufficient to vaccinate the entire at-risk population, logistics result in
      delayed vaccine deployment, and the interaction between members of different
      cities facilitates a wide spatial spread of infection. Limited vaccine, time
      delays, and interaction (or coupling) of cities lead to tradeoffs that impact the
      overall magnitude of the epidemic. These tradeoffs mandate investigation of
      optimal strategies that minimize the severity of the epidemic by prioritizing
      allocation of vaccine to specific subpopulations. We use an SIR model to describe
      the disease dynamics of an epidemic which breaks out in one city and spreads to
      another. We solve a master equation to determine the resulting probability
      distribution of the final epidemic size. We then identify tradeoffs between
      vaccine, time delay, and coupling, and we determine the optimal vaccination
      protocols resulting from these tradeoffs. 

PMID- 27043932
TI  - Impact of beta-glucan on the Fecal Water Genotoxicity of Polypectomized Patients.
AB  - The aim of the study was to determine the effect of beta-glucan on the
      cytotoxicity and genotoxicity of polypectomized patient's fecal water (FW).
      Polypectomized volunteers (n = 69) were randomly assigned to consume bread with
      or without beta-glucan, for 3 months. FW was collected at the beginning (t = 0),
      the 30th and 90th day and 2 wk after the intervention. Cytotoxicity and
      genotoxicity were estimated on Caco-2 cells, using trypan blue exclusion test and
      comet assay, respectively. Gastrointestinal symptoms were recorded and subjects
      kept a 3-day food diary at baseline and after completion. Trypan blue exclusion
      test revealed cell survival of approximately 87% after incubation with FW. The FW
      samples showed 49% genotoxicity at the baseline. Genotoxicity in the intervention
      group decreased during the trial reaching statistical significance on the 90th
      day compared to control. An increase was noticed 2 wk after the trial, but it
      still remained significantly lower compared to control. Group-specific analysis
      for beta-glucan also revealed significant decrease in the genotoxicity on the
      90th day compared to baseline. beta-glucan ingestion in polypectomized patients
      significantly decreased the genotoxicity of their FW. Our findings suggest that
      beta-glucan consumption could possibly provide protection against colon cancer
      development.

PMID- 27043934
TI  - ORBKIT: A modular python toolbox for cross-platform postprocessing of quantum
      chemical wavefunction data.
AB  - ORBKIT is a toolbox for postprocessing electronic structure calculations based on
      a highly modular and portable Python architecture. The program allows computing a
      multitude of electronic properties of molecular systems on arbitrary spatial
      grids from the basis set representation of its electronic wavefunction, as well
      as several grid-independent properties. The required data can be extracted
      directly from the standard output of a large number of quantum chemistry
      programs. ORBKIT can be used as a standalone program to determine standard
      quantities, for example, the electron density, molecular orbitals, and
      derivatives thereof. The cornerstone of ORBKIT is its modular structure. The
      existing basic functions can be arranged in an individual way and can be easily
      extended by user-written modules to determine any other derived quantity. ORBKIT
      offers multiple output formats that can be processed by common visualization
      tools (VMD, Molden, etc.). Additionally, ORBKIT possesses routines to order
      molecular orbitals computed at different nuclear configurations according to
      their electronic character and to interpolate the wavefunction between these
      configurations. The program is open-source under GNU-LGPLv3 license and freely
      available at https://github.com/orbkit/orbkit/. This article provides an overview
      of ORBKIT with particular focus on its capabilities and applicability, and
      includes several example calculations. (c) 2016 Wiley Periodicals, Inc.

PMID- 27043933
TI  - Mutations for Worse or Better: Low-Fidelity DNA Synthesis by SOS DNA Polymerase V
      Is a Tightly Regulated Double-Edged Sword.
AB  - 1953, the year of Watson and Crick, bore witness to a less acclaimed yet highly
      influential discovery. Jean Weigle demonstrated that upon infection of
      Escherichia coli, lambda phage deactivated by UV radiation, and thus unable to
      form progeny, could be reactivated by irradiation of the bacterial host. Evelyn
      Witkin and Miroslav Radman later revealed the presence of the SOS regulon. The
      more than 40 regulon genes are repressed by LexA protein and induced by the
      coproteolytic cleavage of LexA, catalyzed by RecA protein bound to single
      stranded DNA, the RecA* nucleoprotein filament. Several SOS-induced proteins are
      engaged in repairing both cellular and extracellular damaged DNA. There's no
      "free lunch", however, because error-free repair is accompanied by error-prone
      translesion DNA synthesis (TLS), involving E. coli DNA polymerase V (UmuD'2C) and
      RecA*. This review describes the biochemical mechanisms of pol V-mediated TLS.
      pol V is active only as a mutasomal complex, pol V Mut = UmuD'2C-RecA-ATP. RecA*
      donates a single RecA subunit to pol V. We highlight three recent insights. (1)
      pol V Mut has an intrinsic DNA-dependent ATPase activity that governs polymerase
      binding and dissociation from DNA. (2) Active and inactive states of pol V Mut
      are determined at least in part by the distinct interactions between RecA and
      UmuC. (3) pol V is activated by RecA*, not at a blocked replisome, but at the
      inner cell membrane.

PMID- 27043935
TI  - pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted
      Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment.
AB  - Despite the exciting advances in cancer chemotherapy over past decades, drug
      resistance in cancer treatment remains one of the primary reasons for therapeutic
      failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near
      infrared (NIR) photothermal effect are developed to circumvent the drug
      resistance in cancer treatment. The polymeric prodrug micelles are stable in
      physiological environment, while exhibit fast doxorubicin (DOX) release in acidic
      condition and significant temperature elevation under NIR laser irradiation.
      Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug
      conjugation endow them with prolonged circulation time and reduced premature drug
      release during circulation to conduct tumor site-specific chemotherapy. The
      polymeric prodrug micelles combined with NIR laser irradiation could
      significantly enhance intracellular DOX accumulation and synergistically induce
      the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site
      specific chemotherapy combined with hyperthermia effect induces significant
      inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results
      demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for
      hyperthermia-assisted site-specific chemotherapy present an effective approach to
      reverse drug resistance. 

PMID- 27043936
TI  - Changes in Classification of Follicular Thyroid Cancers.

PMID- 27043937
TI  - Arabidopsis heterotrimeric G proteins regulate immunity by directly coupling to
      the FLS2 receptor.
AB  - The Arabidopsis immune receptor FLS2 perceives bacterial flagellin epitope flg22
      to activate defenses through the central cytoplasmic kinase BIK1. The
      heterotrimeric G proteins composed of the non-canonical Galpha protein XLG2, the
      Gbeta protein AGB1, and the Ggamma proteins AGG1 and AGG2 are required for FLS2
      mediated immune responses through an unknown mechanism. Here we show that in the
      pre-activation state, XLG2 directly interacts with FLS2 and BIK1, and it
      functions together with AGB1 and AGG1/2 to attenuate proteasome-mediated
      degradation of BIK1, allowing optimum immune activation. Following the activation
      by flg22, XLG2 dissociates from AGB1 and is phosphorylated by BIK1 in the N
      terminus. The phosphorylated XLG2 enhances the production of reactive oxygen
      species (ROS) likely by modulating the NADPH oxidase RbohD. The study
      demonstrates that the G proteins are directly coupled to the FLS2 receptor
      complex and regulate immune signaling through both pre-activation and post
      activation mechanisms. 

PMID- 27043938
TI  - Determinants of daily path length in black and gold howler monkeys (Alouatta
      caraya) in northeastern Argentina.
AB  - Models used to explain the social organization of primates suggest that variation
      in daily path length (DPL) is a response to variation in resource distribution
      and the intensity of intragroup feeding competition. However, daily path length
      may be affected by a number of other factors including the availability and
      distribution of nutritionally complementary food items, temperature which can
      influence activity budget, patterns of subgrouping, and the frequency and
      function of intergroup encounters. In this 6-month study (total 495 hr of
      quantitative data), we examined daily path lengths in two neighboring groups of
      black and gold howler monkeys (Alouatta caraya) inhabiting a semi-deciduous
      gallery forest in San Cayetano (27 degrees  30'S, 58 degrees  41'W), in the
      northwest province of Corrientes, Argentina. Both study groups were of similar
      size and composition. We identified relationships across groups between time
      spent feeding on fruits, leaves, and flowers, the number of trees visited, group
      spread, frequency of intergroup encounters, mean daily temperature, and DPL. Our
      results suggest that variation in food availability had a significant impact on
      howler ranging behavior by increasing DPL under conditions of high immature and
      mature fruit availability, and by decreasing DPL with increased availability and
      increased time invested in feeding on mature leaves. These results do not support
      the contention that a reduction in food availability or an increase in within
      group feeding competition increased DPL in black and gold howler monkeys. DPL in
      black and gold howlers is influenced by several interrelated factors. In this
      regard we suggest that models of socio-ecology and ecological constraints need to
      reconsider how factors such as individual nutritional requirements, social
      tolerance and group cohesion, and the spatial and temporal availability of
      preferred and nearby food resources influence primate ranging behavior. Am. J.
      Primatol. 78:825-837, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27043942
TI  - Genome-Wide Host-Pathogen Interaction Unveiled by Transcriptomic Response of
      Diamondback Moth to Fungal Infection.
AB  - Genome-wide insight into insect pest response to the infection of Beauveria
      bassiana (fungal insect pathogen) is critical for genetic improvement of fungal
      insecticides but has been poorly explored. We constructed three pairs of
      transcriptomes of Plutella xylostella larvae at 24, 36 and 48 hours post
      treatment of infection (hptI) and of control (hptC) for insight into the host
      pathogen interaction at genomic level. There were 2143, 3200 and 2967 host genes
      differentially expressed at 24, 36 and 48 hptI/hptC respectively. These infection
      responsive genes (~15% of the host genome) were enriched in various immune
      processes, such as complement and coagulation cascades, protein digestion and
      absorption, and drug metabolism-cytochrome P450. Fungal penetration into cuticle
      and host defense reaction began at 24 hptI, followed by most intensive host
      immune response at 36 hptI and attenuated immunity at 48 hptI. Contrastingly, 44%
      of fungal genes were differentially expressed in the infection course and
      enriched in several biological processes, such as antioxidant activity,
      peroxidase activity and proteolysis. There were 1636 fungal genes co-expressed
      during 24-48 hptI, including 116 encoding putative secretion proteins. Our
      results provide novel insights into the insect-pathogen interaction and help to
      probe molecular mechanisms involved in the fungal infection to the global pest. 

PMID- 27043943
TI  - Optimum treatment of congenital cytomegalovirus infection.
AB  - Congenital cytomegalovirus infection affects 0.7% of live births and is the
      leading cause of congenital neurological handicaps of infectious origin. However,
      systematic screening of this infection has not been implemented in pregnancy or
      at birth in any country. This apparent paradox has been justified by the
      unavailability of an efficient vaccine and by the scarcity of data available on
      the treatment of congenital CMV. However, in the last decade interesting new data
      on the management of this congenital infection has emerged including new results
      on both neonatal and postnatal treatments. This review provides an update on the
      potential benefits of antiviral treatment and on passive immunisation both in the
      neonatal and the antenatal periods. These suggest a benefit to a proactive
      approach for neonatal and prenatal congenital infections. 

PMID- 27043944
TI  - Intracellular Golgi Complex organization reveals tissue specific polarity during
      zebrafish embryogenesis.
AB  - BACKGROUND: Cell polarity is essential for directed migration of mesenchymal
      cells and morphogenesis of epithelial tissues. Studies in cultured cells indicate
      that a condensed Golgi Complex (GC) is essential for directed protein trafficking
      to establish cell polarity underlying directed cell migration. Dynamic changes of
      the GC intracellular organization during early vertebrate development remain to
      be investigated. RESULTS: We used antibody labeling and fusion proteins in vivo
      to study the organization and intracellular placement of the GC during early
      zebrafish embryogenesis. We found that the GC was dispersed into several puncta
      containing cis- and trans-Golgi Complex proteins, presumably ministacks, until
      the end of the gastrula period. By early segmentation stages, the GC condensed in
      cells of the notochord, adaxial mesoderm, and neural plate, and its intracellular
      position became markedly polarized away from borders between these tissues.
      CONCLUSIONS: We find that GC is dispersed in early zebrafish cells, even when
      cells are engaged in massive gastrulation movements. The GC accumulates into
      patches in a stage and cell-type specific manner, and becomes polarized away from
      borders between the embryonic tissues. With respect to tissue borders,
      intracellular GC polarity in notochord is independent of mature apical/basal
      polarity, Wnt/PCP, or signals from adaxial mesoderm. Developmental Dynamics
      245:678-691, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27043945
TI  - Increased carcinoembryonic antigen (CEA) following neoadjuvant chemotherapy
      predicts poor prognosis in patients that undergo hepatectomy for liver-only
      colorectal metastases.
AB  - BACKGROUND: The importance of preoperative chemotherapy in a multimodality
      management of patients with colorectal liver metastases (CRLM) has been
      demonstrated. We analyse the carcinoembryonic antigen (CEA) changes following
      neoadjuvant chemotherapy in patients with CRLM who underwent liver resection.
      METHODS: The final cohort included 107 eligible patients. Increased CEA levels
      following neoadjuvant chemotherapy were defined as the increase of baseline CEA
      level at diagnosis of CRLM compared with the CEA level after completion of
      neoadjuvant chemotherapy. Disease-free survival (DFS), post-recurrence survival
      (PRS) and overall survival (OS) were calculated using both Kaplan-Meier and
      multivariate Cox-regression methods. RESULTS: CEA increase was associated with
      decreased PRS and OS (HR 2.69; 95 % CI, 1.28-5.63; p = 0.009, and HR 2.50; 95 %
      CI, 1.12-5.56; p = 0.025, respectively) in multivariate analysis, but there was
      no association between CEA changes and DFS. CEA increase was only associated with
      disease progression during preoperative chemotherapy (p = 0.014). Interestingly,
      this association was not absolute, as only 5 of the 11 patients with disease
      progression demonstrated CEA increase. Regarding the remaining 12 patients with
      CEA increase, according to RECIST criteria, eight patients demonstrated partial
      response and four patients stable disease. CONCLUSION: In this study, we
      demonstrated the CEA increase following neoadjuvant chemotherapy as an adverse
      prognostic factor for PRS, and OS but not for DFS in patients undergoing liver
      resection for liver-only colorectal metastases.

PMID- 27043946
TI  - Influence of different positioning of a local pain catheter on postoperative pain
      after paramedian laparotomy-a blinded, randomized trial.
AB  - BACKGROUND: Continuous application of local anaesthetics reduces postoperative
      pain after different approaches for laparotomy. In this randomized, blinded
      trial, we investigated the effect of continuous application of local anaesthetics
      after paramedian laparotomy either with subfascial or subcutaneous catheter in
      addition to a standardized systemic analgesia. MATERIALS AND METHODS: Patients
      with stage III/IV melanoma and indication for radical iliac lymph node dissection
      (RILND) were randomized to a continuous application of a local anaesthetic
      through either a subfascial or subcutaneous catheter. Participants and those
      assessing the outcomes were blinded. The main outcome criterion was the pain
      level on the first postoperative morning while exercising measured with a visual
      analogue scale. Minor criteria were the pain measured by the area-under-curve
      until the third postoperative day, the patient's satisfaction with analgesic
      treatment, the analgesic requirement, the overall complications and the day of
      discharge. RESULTS: Fifty-two patients were evaluated. Pain therapy was
      sufficient in both groups during the postoperative course while resting and
      during mobilization. There were no significant differences regarding the main and
      minor outcome criteria. Doses of additional analgesics did not differ between
      groups. No adverse events or side effects were observed. CONCLUSION: For patients
      who undergo paramedian laparotomy, none of the investigated techniques is
      superior to the other at a median pain level under visual analogue scale (VAS) 30
      mm on the first postoperative morning. TRIAL REGISTRATION NUMBER: DRKS00003632
      (German Register of Clinical Trials).

PMID- 27043947
TI  - Detecting eating disorder patients in a general practice setting: a systematic
      review of heterogeneous data on clinical outcomes and care trajectories.
AB  - PURPOSE: The incidence and prevalence of eating disorders (ED) is low in general
      practice (GP) settings. Studies in secondary care suggest that the general
      practitioner has an important role to play in the early detection of patients
      with EDs. The aim of this study was to describe the effect (clinical outcomes and
      care trajectory) of screening for EDs among patients in general practice
      settings. METHODS: A systematic review was conducted on Medline, PsycINFO,
      CINAHL, Embase and WOS. The studies included were to have been carried out in a
      primary care setting, with screening explicitly performed in GP practices and
      follow-up information. RESULTS: Ten studies met the inclusion criteria. For all
      ED patients, there was an increase in the frequency of consultations in GP
      setting, referrals to psychiatric resources and drug prescriptions such as
      antidepressants, following screening procedures. Clinical outcomes remained
      unclear and heterogeneous. One study focused on the course and outcome of ED
      patients identified by screening in the GP setting and reported recovery for
      anorexia nervosa (AN) and BN in more than half of the cases, after 4.8 years of
      mean follow-up. In this study, early age at detection predicted better recovery.
      CONCLUSION: Most of the literature on the role of the GP in screening for and
      managing EDs consists of opinion papers and original studies designed in a
      secondary care perspective. The impact of systematically screening for EDs in a
      primary care setting is not clarified and requires further investigation in
      collaborative cohort studies with a patient-centered approach, and outcomes
      focused on symptoms.

PMID- 27043948
TI  - Obesity or obesities? Controversies on the association between body mass index
      and premature mortality.
AB  - Obesity is still defined on the basis of body mass index (BMI) and BMI in itself
      is generally accepted as a strong predictor of overall early mortality. However,
      an inverse association between BMI and mortality has been reported in patients
      with many disease states and in several clinical settings: hemodialysis,
      cardiovascular diseases, hypertension, stroke, diabetes, chronic obstructive
      pulmonary disease, surgery, etc. This unexpected phenomenon is usually called
      obesity-survival paradox (OP). The contiguous concepts of metabolically healthy
      obesity (MHO, a phenotype having BMI >= 30 but not having any metabolic syndrome
      component and having a homeostasis model assessment of insulin resistance, HOMA,
      <2.5) and metabolically obese normal weight (MONW, normal-weight individuals
      displaying obesity-related phenotypic characteristics) have received a great deal
      of attention in recent years. The interactions that link MHO, MONW and OP with
      body composition, fat distribution, aging and cardiorespiratory fitness are other
      crucial areas of research. The article is an introductory narrative overview of
      the origin and current use of the concepts of MHO, MONW and OP. These phenomena
      are very controversial and appear as a consequence of the frail current
      diagnostic definition of obesity based only on BMI. A new commonly established
      characterization and classification of obesities based on a number of variables
      is needed urgently. 

PMID- 27043949
TI  - Systematic Review of Efficacy, Pharmacokinetics, and Administration of
      Intraventricular Aminoglycosides in Adults.
AB  - Due to increasing prevalence of intracranial device use and multidrug-resistant
      and nosocomial organisms, central nervous system (CNS) infections requiring
      treatment with intraventricular (IVT) aminoglycosides are becoming increasingly
      common. This article systematically reviews IVT aminoglycoside literature in
      adults and integrates available evidence to serve as a practical reference for
      clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015),
      PubMed (1966 to December 2015), Google, and Google Scholar were searched using
      the term aminoglycoside combined individually with the terms IVT, meningitis,
      shunt infection, ventriculitis, and cerebral spinal fluid. Eighteen articles were
      included. IVT aminoglycosides were assessed in meningitis, ventriculitis,
      intracranial device infections and neurosurgery prophylaxis. No serious adverse
      effects following IVT aminoglycoside were reported. Dosages ranged from IVT
      gentamicin 4-10 mg daily, IVT tobramycin 5-10 mg daily, and IVT amikacin 5-50 mg
      daily. Duration of therapy should be individualized; however, continuing IVT
      antibiotics for 3 days and up to 21 days after cerebrospinal fluid (CSF)
      sterilization has been reported in literature. Most studies included concomitant
      intravenous antibiotic use. Therapeutic drug monitoring (TDM) was reported in
      five studies, with varying timing of CSF concentrations obtained. No clear
      relationship between CSF levels and efficacy or toxicity was evident. Based on
      current literature, IVT aminoglycosides for the treatment of sensitive gram
      negative meningitis, ventriculitis, and CNS device-associated infections appear
      safe and effective. Optimal dosing regimens are unclear. It is reasonable to
      initiate IVT aminoglycoside at lowest dose in combination with IV therapy and
      continuing post CSF sterilization. Preservative-free formulations should be
      utilized to minimize adverse drug reactions. TDM should not be routinely utilized
      but reserved for more complicated patients. Further pharmacokinetic and clinical
      trials of IVT aminoglycosides are necessary to fill current therapeutic gaps. Due
      to the relatively limited cases of IVT aminoglycoside utilization, prospective,
      randomized, controlled trials are likely not feasible, and clinicians will have
      to rely on data from non-randomized and/or retrospective studies.

PMID- 27043950
TI  - Misdiagnosis of spinal subacute combined degeneration in a patient with elevated
      serum B12 concentration and sensory deficit level.

PMID- 27043951
TI  - Editorial Comment to Robotic transmural ablation of bladder tumors using high
      intensity focused ultrasound: Experimental study.

PMID- 27043952
TI  - Effectiveness of Trauma-Focused Cognitive Behavioral Therapy for Children and
      Adolescents: A Randomized Controlled Trial in Eight German Mental Health Clinics.
AB  - BACKGROUND: Trauma-focused cognitive behavioral therapy (Tf-CBT) is efficacious
      for children and adolescents with posttraumatic stress symptoms (PTSS). Its
      effectiveness in clinical practice has still to be investigated. AIMS: To
      determine whether Tf-CBT is superior to waiting list (WL), and to investigate the
      predictors of treatment response. METHOD: We conducted a single-blind parallel
      group randomized controlled trial in eight German outpatient clinics with the
      main inclusion criteria of age 7-17 years, symptom score >=35 on the Clinician
      Administered PTSD Scale for Children and Adolescents (CAPS-CA), and caregiver
      participation. Patients were randomly assigned to 12 sessions of Tf-CBT (n = 76)
      or a WL (n = 83). The primary outcome was the CAPS-CA symptom score assessed at 4
      months by blinded evaluators. The secondary measures were diagnostic status, the
      Children's Global Assessment Scale (CGAS), self-reported and caregiver-reported
      PTSS (UCLA-PTSD Reaction Index), the Child Posttraumatic Cognitions Inventory
      (CPTCI), the Children's Depression Inventory (CDI), the Screen for Child Anxiety-
      Related Emotional Disorders (SCARED), the Child Behavior Checklist (CBCL/4-18),
      and the Quality of Life Inventory for Children. RESULTS: Intention-to-treat
      analyses showed that Tf-CBT was significantly superior to WL on the CAPS-CA (Tf
      CBT: baseline = 58.51 +/- 17.41; 4 months = 32.16 +/- 26.02; WL: baseline = 57.39
      +/- 16.05; 4 months = 43.29 +/- 25.2; F1, 157 = 12.3; p = 0.001; d = 0.50), in
      terms of secondary measures of the CGAS, UCLA-PTSD-RI, CPTCI, CDI, SCARED, and
      CBCL/4-18, but not in terms of quality of life. Age and comorbidity significantly
      predicted treatment response. CONCLUSIONS: Tf-CBT is effective for children and
      adolescents with heterogeneous trauma types in German service settings. Younger
      patients with fewer comorbid disorders show most improvement.

PMID- 27043953
TI  - A novel de-novo frameshift mutation of the ASXL1 gene in a classic case of
      Bohring-Opitz syndrome.

PMID- 27043954
TI  - Tetra-Antimony(III)-Bridged 18-Tungsto-2-Arsenates(V), [(LSb(III))4(A-alpha
      As(V)W9O34)2](10-) (L = Ph, OH): Turning Bioactivity On and Off by Ligand
      Substitution.
AB  - Two tetra-antimony(III)-bridged, sandwich-type 18-tungsto-2-arsenates(V),
      [(LSb(III))4(A-alpha-As(V)W9O34)2](10-) (L = Ph (1), OH (2)), were prepared and
      fully characterized in the solid state and in solution. Both polyanions are
      stable in aqueous physiological medium for at least 24 h (at concentrations >=2.5
      * 10(-6) M). Despite the presence of an isostructural tetra-antimony(III) motif
      in 1 and 2, distinctly different antibacterial activity was observed for both
      polyanions. The minimum inhibitory concentrations (MIC) of 1 (7.8-62.5 MUg/mL) is
      lower than for any other organoantimony(III)-containing polyoxometalate reported
      to date. 

PMID- 27043955
TI  - Does Closeness to Someone Who Is Gay, Lesbian, or Bisexual Influence Etiology
      Beliefs About Homosexuality?
AB  - Research suggests that contact with sexual minorities and etiology beliefs
      regarding the origins of homosexuality are associated with antigay bias; however,
      factors related to etiology beliefs have received little empirical attention. Our
      primary research question is: Does closeness to someone who is gay, lesbian, or
      bisexual influence etiology beliefs? Students (n = 851) from four U.S.
      universities completed an anonymous survey, and regression results indicated that
      contact and closeness were not significantly associated with etiology beliefs.
      Because both contact and relationship closeness were associated with antigay
      attitudes, and closeness demonstrated the largest effect, we tested three
      alternative structural equation models to determine if contact and closeness
      mediated etiology beliefs. Results suggested that contact and the degree of
      closeness are indirectly associated with students' etiology beliefs through
      antigay bias.

PMID- 27043956
TI  - Fungal sensitisation in severe asthma is associated with the identification of
      Aspergillus fumigatus in sputum.
AB  - BACKGROUND: Fungal sensitisation is an important factor in severe asthma, not
      only for allergic bronchopulmonary aspergillosis (ABPA) but also the more
      recently described severe asthma with fungal sensitisation (SAFS). It is not
      known whether these diseases are driven by the presence of airway fungal
      colonisation. We aimed to determine if both SAFS and ABPA were associated with
      airway isolation of Aspergillus fumigatus and whether the frequency of isolation
      changed following anti-fungal treatment. METHODS: Sputum samples were collected
      from patients with SAFS, ABPA and a control group without fungal sensitisation.
      We recorded details of antifungal treatment, serum IgE and A. fumigatus specific
      IgE levels. In a subgroup (n = 9) we recorded serial sputum PCR measurements
      before and during itraconazole therapy. RESULTS: 244 sputum samples were provided
      by 135 patients, 41(17%) ABPA, 168(69%) SAFS, and 35(14%) controls. Sputum
      Aspergillus fumigatus PCR was positive in 61 SAFS patients (70%) and 6 ABPA
      patients (50%) not on anti-fungal treatment at the time of the test, compared to
      3 (9%) in controls (chi(2) = 37.90, p < 0.001). Consequently, 19 patients with
      SAFS who were taking antifungal treatment (23%) were significantly less likely to
      be PCR positive than the 61 patients not on treatment (70%) (chi(2) = 36.66, p <
      0.001). All 9 patients assessed serially during therapy had positive sputum PCR
      pre-treatment and all became negative during itraconazole treatment. CONCLUSION:
      We have shown that isolation of fungus from the airway of severe asthma patients
      with fungal sensitisation is very common, supporting the hypothesis of a
      mechanistic link between fungal colonisation and sensitisation.

PMID- 27043957
TI  - Statin use and the risk of colorectal adenoma: A meta-analysis.
AB  - BACKGROUND: Although statin use has been reported to reduce the risk of
      colorectal cancer beyond its cholesterol-lowering effects, the benefit of statins
      against colorectal adenoma has not been fully clarified. We aimed to investigate
      the association between statin use and the risk of colorectal adenoma. METHODS:
      We conducted a systematic literature search on MEDLINE, EMBASE, and the Cochrane
      Library using the primary keywords "adenoma," "polyp," "colorectal," "colon,"
      "rectal," "rectum," "neoplasia," "neoplasm," "statin," "3-hydroxy-3
      methylglutaryl-coenzyme A," and "HMG-CoA." Studies were included if they
      evaluated the association between statin use and adenoma and reported relative
      risks (RRs) or odds ratios or provided data for estimation. Pooled estimates were
      calculated using the random-effects model. RESULTS: Six studies including 13 239
      patients were analyzed. The median proportion of patients with any adenoma was
      29.7% (range, 20.9-38.4%) in patients taking statins and 31.2% (range, 19.6
      63.4%) in patients not taking statins across included studies. The median
      proportion of patients with advanced adenoma in those taking statins was 7.7%
      (range, 3.1-27.2%), whereas that in patients not taking statins was 11.3% (range,
      3.5-32.4%). On meta-analysis, statin use did not significantly affect the risk of
      any adenoma (pooled RR = 0.901; 95% confidence interval [CI], 0.735-1.104);
      however, it was associated with a lower risk of advanced adenoma (pooled RR =
      0.833; 95% CI, 0.750-0.925). CONCLUSIONS: Statin use seems to be associated with
      a reduced risk of advanced adenoma, but not any adenoma. Statins may prevent
      neoplastic progression of adenomas rather than the development of adenomas.

PMID- 27043958
TI  - Dietary restriction: could it be considered as speed bump on tumor progression
      road?
AB  - Dietary restrictions, including fasting (or long-term starvation), calorie
      restriction (CR), and short-term starvation (STS), are considered a strong
      rationale that may protect against various diseases, including age-related
      diseases and cancer. Among dietary approaches, STS, in which food is not consumed
      during designed fasting periods but is typically not restricted during designated
      feeding periods, seems to be more suitable, because other dietary regimens
      involving prolonged fasting periods could worsen the health conditions of cancer
      patients, being they already naturally prone to weight loss. Until now, the
      limited amount of available data does not point to a single gene, pathway, or
      molecular mechanism underlying the benefits to the different dietary approaches.
      It is well known that the healthy effect is mediated in part by the reduction of
      nutrient-related pathways. The calorie restriction and starvation (long- and
      short-term) also suppress the inflammatory response reducing the expression, for
      example, of IL-10 and TNF-alpha, mitigating pro-inflammatory gene expression and
      increasing anti-inflammatory gene expression. The dietary restriction may
      regulate both genes involved in cellular proliferation and factors associated to
      apoptosis in normal and cancer cells. Finally, dietary restriction is an
      important tool that may influence the response to chemotherapy in preclinical
      models. However, further data are needed to correlate dietary approaches with
      chemotherapeutic treatments in human models. The aim of this review is to discuss
      the effects of various dietary approaches on the cancer progression and therapy
      response, mainly in preclinical models, describing some signaling pathways
      involved in these processes. 

PMID- 27043959
TI  - Platelet-rich plasma reduces skin flap inflammatory cells infiltration and
      improves survival rates through induction of angiogenesis: An experiment in
      rabbits.
AB  - BACKGROUND: This study was conducted to evaluate the effects of platelet-rich
      plasma (PRP) on flap survival in an experimental rabbit model. METHODS:
      Symmetrical rectangular dorsal cutaneous flaps (8 * 2 cm) were elevated in 15
      rabbits. The rabbits were randomly divided into a 3-day group (n = 5), a 7-day
      group (n = 5), and a 14-day group (n = 5). Either side of the dorsum was selected
      for injection of PRP into the flap basal surface, while the other side received
      an equal volume of saline as a control. The flaps were immediately sutured back,
      after which the flap survival was measured and histology specimens were collected
      at 3, 7, and 14 days. RESULTS: Platelet-rich plasma significantly improved flap
      survival rates of the PRP side flaps relative to the control in the 3-day (74.4%
      +/- 4.7% vs 65.8% +/- 6.8%; p < 0.05), 7-day (72.4% +/- 7.5% vs 58.5% +/- 7.0%; p
      < 0.05), and 14-day (74.5% +/- 5.0% vs 65.0% +/- 5.4%; p < 0.05) groups.
      Histological analysis revealed significantly fewer inflammatory cells and an
      increased blood vessel density in the platelet-rich plasma side flap vs the blank
      control side flap. CONCLUSION: Platelet-rich plasma (PRP) promotes the survival
      of random rabbit flaps and, therefore, represents a promising treatment to
      prevent skin flap necrosis in reconstructive and plastic surgery.

PMID- 27043960
TI  - Sex-based differences in lymphocyte proliferation in the spleen after vanadium
      inhalation.
AB  - Vanadium (V) is a transition metal often adhered to particulate matter and
      released into the atmosphere as vanadium pentoxide (V2O5) by the burning of
      fossil fuels. This air pollutant causes adverse effects in the immune system.
      Lymphocytosis and splenomegaly have been reported with increased white pulp in
      mice after V inhalation. The effect of V on the immune system as related to sex
      has been poorly investigated. This study sought to determine if V inhalation (a)
      produced lymphoproliferation that could explain the changes previously observed
      in the spleen and in peripheral blood lymphocyte counts and (b) whether any
      observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a
      specific proliferation marker, was made in the spleens of CD-1 male and female
      mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg
      V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens
      of control mice exposed to vehicle (filtered air). The results showed that in
      male mice there was a significant increase in percentage of Ki-67 immunopositive
      lymphocytes starting from the second week and until the end of the exposure. The
      Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls
      the signal was only nuclear. In female mice, V inhalation singificantly increased
      the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67
      signal was observed only in the nucleus of lymphocytes from the control and
      exposed females. The results here help to explain the splenomegaly and
      lymphocytosis observed previously in male mice and support the
      lymphoproliferative effect induced by V. Lastly, the finding that there was a sex
      difference in the effect of vanadium on lymphocyte proliferation suggests a role
      for sex hormones in potential protection against V immunotoxicity; however,
      further studies are needed to support this hypothesis.

PMID- 27043961
TI  - Thoracoscopic Implant of Neurostimulator for Delayed Gastric Conduit Emptying
      After Esophagectomy.
AB  - BACKGROUND AND AIMS: Gastroparesis is a clinical syndrome characterized by
      delayed gastric emptying in the absence of mechanical outlet obstruction. Use of
      the denervated stomach as an esophageal substitute is a common cause of transient
      gastroparesis. Gastric electrostimulation through a thoracotomy approach has
      previously been reported to be effective in patients with medically refractory
      postesophagectomy gastroparesis. We report the first thoracoscopic implant of a
      gastric neurostimulator. METHODS AND RESULTS: A 57-year-old woman underwent Ivor
      Lewis esophagectomy for early stage (T1N0) adenocarcinoma in 2007. She
      progressively developed progressive dysphagia, regurgitation, and a 29-kg weight
      loss. The barium swallow study and upper gastrointestinal endoscopy showed a
      dilated intrathoracic stomach without evidence of mechanical obstruction.
      Erythromycin and multiple endoscopic dilatations of the pylorus were
      unsuccessful, and eventually, a feeding jejunostomy was performed. At the time
      the patient was referred to our outpatient clinic, she was unable to eat and
      depended on total enteral nutrition. Computed tomography, endoscopy, and barium
      swallow study confirmed that there was no evidence of recurrent adenocarcinoma or
      mechanical gastric outlet obstruction. A gastric electrostimulator system
      (Enterra((r))) was implanted through a right thoracoscopic access and connected
      to the gastric conduit. At 6-month follow-up, there was a significant improvement
      of the total symptom score and quality of life. CONCLUSIONS: Electrostimulation
      of the gastric conduit after esophagectomy can safely be performed through a
      thoracoscopic approach and may represent a reasonable therapeutic option in
      patients with symptomatic and medically refractory delayed gastric emptying.

PMID- 27043962
TI  - Pediatric Maxillofacial Trauma: A Review of 156 Patients.
AB  - PURPOSE: To review the epidemiology and management of facial fractures in a
      pediatric population. MATERIALS AND METHODS: This study was a retrospective
      review of patients younger than 18 years who presented to a pediatric emergency
      department during a 5-year period in an urban, academic, level 1 designated
      trauma center. RESULTS: Of the 156 patients identified, most were boys (87%) and
      the mean age was 13.5 years (standard deviation, 4.9 yr; interquartile range, 12
      to 17 yr). The most common mechanism of injury was assault (48.1%). Mandibular
      fractures (40.7%) were most common. Multiple fractures occurred in 26.9% of
      patients. Concomitant injuries occurred in 73.7% of patients, most commonly
      concussions (39.1%). Intracranial hemorrhages were associated with panfacial (P =
      .005), frontal (P = .001), and orbital (P = .04) fractures. Most patients (91.7%)
      were admitted, and nonoperative repair was undertaken in 57.1%. There was an
      independent association of surgical intervention with age older than 14 years and
      with mandibular fractures (P < .01). CONCLUSIONS: Assault was the most common
      mechanism of injury and mandibular fracture was the most commonly encountered.
      Concomitant nonfacial injuries occurred in most patients. Patients sustaining
      panfacial, frontal, and orbital fractures should provoke an evaluation for other
      intracranial injuries. Children older than 14 years and those with mandibular
      fractures should prompt mobilization of resources for operative repair.

PMID- 27043963
TI  - Hepatitis B discrimination in everyday life by rural migrant workers in Beijing.
AB  - BACKGROUND: In China, the hepatitis B virus (HBV) is a particularly challenging
      public health issue, with an estimated 90 million chronic hepatitis B carriers
      accounting for almost 7% of the population. Health-related discrimination can
      serve as a barrier to prevention and care for infectious diseases, such as HBV,
      degrade the HBV sufferers' quality of life and limit HBV patients' employment
      opportunities. While rural migrants account for up to 40% of the total urban
      population in the developed cities in China, there has been no study of the
      discrimination behavior of rural migrant workers toward HBV carriers. OBJECTIVE:
      This study evaluates the discrimination behavior of rural migrant workers toward
      HBV carriers and patients and proposes public policy recommendations to address
      discrimination and stigma. METHODS: The sample comprised 903 rural adults, aged
      over 18 years old, who migrated to Beijing. Using a face-to-face interview, we
      surveyed rural migrants' demographic characteristics, knowledge of HBV and
      discrimination against HBV carriers. Descriptive statistics were used to
      characterize the study population, HBV stigma and knowledge of HBV. Three
      discrimination levels (no-mild, medium and severe discrimination) were modeled
      using multiple logistic regression. RESULTS: Rural migrants to Beijing had a mean
      age of 36 years, were overwhelmingly married (91.58%), mostly with a junior high
      school or lower education (78.05%) and mainly engaged as temporary workers
      (42.52%) or self-employed (33.78%). Only 30.56% reported that they had been
      vaccinated against HBV. On the 0-10 discrimination scale, rural migrants rated
      6.24, with only 4.54% displaying no sign of HBV-related discrimination. The high
      discrimination score occurred alongside a low mean knowledge of HBV (7.61 on the
      1-22 ranking of HBV knowledge). Multiple logistic regression results suggest an
      inverse relationship between discrimination levels and HBV knowledge, especially
      knowledge about treatment and transmission routes. The "fear of being infected
      with HBV" and being HBV vaccinated was positively associated with HBV-related
      discrimination. Unemployed rural migrants were more likely to exhibit severe HBV
      related discrimination than other occupational groups. Personal attributes, such
      as gender, age, marital status and education level were not associated with the
      level of discrimination. CONCLUSIONS: Knowledge of HBV, its transmission and
      treatment, and the fear of HBV infection were key features in understanding HBV
      discrimination by rural migrant workers. To reduce discrimination, HBV public
      health education campaigns need to focus on both knowledge about HBV and the fear
      of HBV infection. Such campaigns should target rural migrant subgroups, such as
      unemployed rural migrant workers.

PMID- 27043964
TI  - Changes in activity participation following traumatic brain injury.
AB  - Traumatic brain injury (TBI) often results in impairments in cognitive skills as
      well as depression. As a result of these changes in cognition and mood,
      individuals with TBI may reduce their levels of participation and often report
      reduced health-related quality of life (HrQOL). The current study compares levels
      of past and present activity participation between healthy participants and
      persons with TBI using a client-centred approach in measurement. We additionally
      examine the relationship between activity participation, emotional functioning
      and HrQOL in persons with TBI. Fifty-two individuals with TBI who live in the
      community and 30 healthy age-matched controls performed a battery of cognitive
      tests and rated their affective symptomatology and activity participation (using
      the Activity Card Sort Test). Participants with TBI reported significantly lower
      current activity participation compared to controls. Current levels of activity
      and participation in the TBI sample were significantly related to age, time since
      injury, and HrQOL. Additionally, depressive symptomatology was significantly
      associated with HrQOL, but not with activity participation. Following TBI, levels
      of activity participation are reduced in most aspects of life, but more
      profoundly in social activities, high demand leisure activities and household
      activities. Additionally, high levels of depressive symptoms are associated with
      negative reports of HrQOL, regardless of current levels of activity
      participation.

PMID- 27043965
TI  - Role of vacuolar membrane proton pumps in the acidification of protein storage
      vacuoles following germination.
AB  - During soybean (Glycine max (L.) Merrill) seed development, protease C1, the
      proteolytic enzyme that initiates breakdown of the storage globulins beta
      conglycinin and glycinin at acidic pH, is present in the protein storage vacuoles
      (PSVs), the same subcellular compartments in seed cotyledons where its protein
      substrates accumulate. Actual proteolysis begins to be evident 24 h after seed
      imbibition, when the PSVs become acidic, as indicated by acridine orange
      accumulation visualized by confocal microscopy. Imidodiphosphate (IDP), a non
      hydrolyzable substrate analog of proton-translocating pyrophosphatases, strongly
      inhibited acidification of the PSVs in the cotyledons. Consistent with this
      finding, IDP treatment inhibited mobilization of beta-conglycinin and glycinin,
      the inhibition being greater at 3 days compared to 6 days after seed imbibition.
      The embryonic axis does not appear to play a role in the initial PSV
      acidification in the cotyledon, as axis detachment did not prevent acridine
      orange accumulation three days after imbibition. SDS-PAGE and immunoblot analyses
      of cotyledon protein extracts were consistent with limited digestion of the 7S
      and 11S globulins by protease C1 starting at the same time and proceeding at the
      same rate in detached cotyledons compared to cotyledons of intact seedlings.
      Embryonic axis removal did slow down further breakdown of the storage globulins
      by reactions known to be catalyzed by protease C2, a cysteine protease that
      normally appears later in seedling growth to continue the storage protein
      breakdown initiated by protease C1. 

PMID- 27043966
TI  - Identification and segmentation of obscure pectoral muscle in mediolateral
      oblique mammograms.
AB  - OBJECTIVE: X-ray mammography is a widely used and reliable method for detecting
      pre-symptomatic breast cancer. One of the difficulties in automatically
      computerized mammogram analysis is the presence of pectoral muscles in
      mediolateral oblique mammograms because the pectoral muscle does not belong to
      the scope of the breast. The objective of this study is to identify the boundary
      of obscure pectoral muscle in mediolateral oblique mammograms. METHODS: Two
      tentative boundary curves are individually created to be the potential
      boundaries. To find the first tentative boundary, this study finds local extrema,
      prunes weak extrema and then determines an appropriate threshold for identifying
      the brighter tissue, whose edge is considered the first tentative boundary. The
      second tentative boundary is found by partitioning the breast into several
      regions, where each local threshold is tuned based on the local intensity.
      Subsequently, both of these tentative boundaries are used as the reference to
      create a refined boundary by Hough transform. Then, the refined boundary is
      partitioned into quadrilateral regions, in which the edge of this boundary is
      detected. Finally, these reliable edge points are collected to generate the
      genuine boundary by curve fitting. RESULTS: The proposed method achieves the
      least mean square error 4.88 +/- 2.47 (mean +/- standard deviation) and the least
      misclassification error rate (MER) with 0.00466 +/- 0.00191 in terms of MER.
      CONCLUSION: The experimental results indicate that this method performs best and
      stably in boundary identification of the pectoral muscle. ADVANCES IN KNOWLEDGE:
      The proposed method can identify the boundary from obscure pectoral muscle, which
      has not been solved by the previous studies.

PMID- 27043967
TI  - Carcinoma of the lung in the absence of asbestosis: The value of lung fiber
      burden analysis.
AB  - Asbestos is universally recognized as a carcinogen for the lower respiratory
      tract. However, asbestos is a contributory factor in a small fraction of lung
      cancers, the vast majority of which are related to cigarette smoking. The
      challenge for the pathologist is to determine when a lung cancer may be
      attributed to past asbestos exposure. The finding of asbestosis either clinically
      or pathologically is a useful marker for such a determination. However, in the
      absence of asbestosis, it has been suggested that a fiber burden as determined by
      analytical electron microscopy within the range of asbestosis is sufficient for
      determination of a causal contribution. We report here an example of a case of
      lung cancer in which fiber burden studies showed an asbestos concentration within
      the range of asbestosis as determined by scanning electron microscopy (SEM). 

PMID- 27043968
TI  - Norovirus detection from sera of young children with acute norovirus
      gastroenteritis.
AB  - BACKGROUND: Antigenemia and viremia are common in rotavirus infection but only
      few studies have shown norovirus (NoV) RNA in the blood circulation. OBJECTIVES:
      To detect NoV RNA from serum of NoV-infected children and study if NoV RNAemia
      correlates with clinical severity of acute gastroenteritis. STUDY DESIGN: Serum
      specimens were collected from 176 Finnish children with acute NoV
      gastroenteritis. Semi-nested PCR was optimized to detect NoV capsid RNA from
      sera. NoV positive samples were further analyzed by sequencing. RESULTS: NoV RNA
      was found in 11/176 (6.3%) of serum specimens. NoV GII.4 was found in 8 cases and
      GII.3, GII.6 and GII.7 in one case each. The genotypes detected in serum were
      identical to findings in stools in all cases. Most of the NoV RNA detections in
      serum were in young children less than 18 months of age. The clinical features of
      NoV serum-positive cases were not different from NoV serum-negative cases.
      CONCLUSION: NoV RNA in serum is an uncommon finding limited to young children.

PMID- 27043969
TI  - Quantiferon CMV assay in allogenic stem cell transplant patients.

PMID- 27043970
TI  - Combined effects of marinating and gamma-irradiation in ensuring safety,
      protection of nutritional value and increase in shelf-life of ready-to-cook meat
      for immunocompromised patients.
AB  - The aim of this study was to evaluate the effect of combining marinating and
      gamma-irradiation at doses of 1, 1.5 and 3kGy on Escherichia coli O157:H7,
      Salmonella typhimurium and Clostridium sporogenes in raw meat packed under vacuum
      and stored at 4 degrees C and to estimate its safety and shelf-life. Further, the
      effect of combined treatments on sensorial, nutritional values (lipid oxidation,
      concentration of thiamin and riboflavin) and color was evaluated. The study
      demonstrated that the use of marinade in combination with a low dose of gamma
      irradiation (1.5kGy) could act in synergy to reduce to undetectable level of
      pathogenic bacteria and increase the shelf-life of ready-to-cook meat loin
      without affecting its sensorial and nutritional quality. 

PMID- 27043971
TI  - Long-term field application of sewage sludge increases the abundance of
      antibiotic resistance genes in soil.
AB  - Sewage sludge and manure are common soil amendments in crop production; however,
      their impact on the abundance and diversity of the antibiotic resistome in soil
      remains elusive. In this study, by using high-throughput sequencing and high
      throughput quantitative PCR, the patterns of bacterial community and antibiotic
      resistance genes (ARGs) in a long-term field experiment were investigated to gain
      insights into these impacts. A total of 130 unique ARGs and 5 mobile genetic
      elements (MGEs) were detected and the long-term application of sewage sludge and
      chicken manure significantly increased the abundance and diversity of ARGs in the
      soil. Genes conferring resistance to beta-lactams, tetracyclines, and multiple
      drugs were dominant in the samples. Sewage sludge or chicken manure applications
      caused significant enrichment of 108 unique ARGs and MGEs with a maximum
      enrichment of up to 3845 folds for mexF. The enrichment of MGEs suggested that
      the application of sewage sludge or manure may accelerate the dissemination of
      ARGs in soil through horizontal gene transfer (HGT). Based on the co-occurrence
      pattern of ARGs subtypes revealed by network analysis, aacC, oprD and mphA-02,
      were proposed to be potential indicators for quantitative estimation of the co
      occurring ARGs subtypes abundance by power functions. The application of sewage
      sludge and manure resulted in significant increase of bacterial diversity in
      soil, Proteobacteria, Acidobacteria, Actinobacteria and Chloroflexi were the
      dominant phyla (>10% in each sample). Five bacterial phyla (Chloroflexi,
      Planctomycetes, Firmicutes, Gemmatimonadetes and Bacteroidetes) were found to be
      significantly correlated with the ARGs in soil. Mantel test and variation
      partitioning analysis (VPA) suggested that bacterial community shifts, rather
      than MGEs, is the major driver shaping the antibiotic resistome. Additionally,
      the co-occurrence pattern between ARGs and microbial taxa revealed by network
      analysis indicated that four bacterial families might be potential hosts of ARGs.
      These results may shed light on the mechanism underlining the effects of
      amendments of sewage sludge or manure on the occurrence and dissemination of ARGs
      in soil.

PMID- 27043972
TI  - Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors:
      binding energy analysis assisted by molecular docking, ADMET and molecular
      dynamics simulation.
AB  - Visceral leishmaniasis affects people from 70 countries worldwide, mostly from
      Indian, African and south American continent. The increasing resistance to
      antimonial, miltefosine and frequent toxicity of amphotericin B drives an urgent
      need to develop an antileishmanial drug with excellent efficacy and safety
      profile. In this study we have docked series of febrifugine analogues (n = 8813)
      against trypanothione reductase in three sequential docking modes. Extra
      precision docking resulted into 108 ligands showing better docking score as
      compared to two reference ligand. Furthermore, 108 febrifugine analogues and
      reference inhibitor clomipramine were subjected to ADMET, QikProp and molecular
      mechanics, the generalized born model and solvent accessibility study to ensure
      the toxicity caused by compounds and binding-free energy, respectively. Two best
      ligands (FFG7 and FFG2) qualifying above screening parameters were further
      subjected to molecular dynamics simulation. Conducting these studies, here we
      confirmed that 6-chloro-3-[3-(3-hydroxy-2-piperidyl)-2-oxo-propyl]-7-(4-pyridyl)
      quinazolin-4-one can be potential drug candidate to fight against Leishmania
      donovani parasites.

PMID- 27043973
TI  - Medial plantar-to-radial amplitude ratio: does it have electrodiagnostic utility
      in distal sensory polyneuropathy?
AB  - PURPOSE OF THE STUDY: We proposed a new electrophysiological parameter medial
      plantar (MP)-to-radial amplitude ratio (MPRAR), similar to sural-to-radial
      amplitude ratio (SRAR), in the diagnosis of distal sensory polyneuropathy (DSP),
      based on the concept that distal nerves are affected more and earlier than
      proximal nerves in axonal neuropathies. We aimed to investigate the diagnostic
      sensitivity of this parameter in diabetic DSP, together with sensitivities of
      SRAR and MP nerve action potential (NAP) amplitude. MATERIALS AND METHODS: In 124
      healthy controls and 87 diabetic patients with clinically defined DSP and normal
      sural responses, we prospectively performed sensory nerve conduction studies
      (NCS), and evaluated the MP NAP amplitude, MPRAR and SRAR values. We determined
      the lower limits of normal (LLN) of these parameters in the healthy controls and
      calculated their sensitivities and specificities in detecting DSP in diabetic
      patients. RESULTS: MP nerve amplitude and MPRAR values were significantly lower
      in the patient group, compared to controls. However, SRAR values did not differ
      significantly between the two groups. The LLN of MP NAP amplitude was found to be
      4.1 MUV. The cutoff values for SRAR and MPRAR were determined as 0.24 and 0.16,
      respectively. MPRAR was abnormal in 21.8% of patients. However, the most
      sensitive parameter in detection of DSP was MP NAP amplitude, which showed a
      sensitivity of 31% and a specificity of 100%. CONCLUSIONS: Although MPRAR is more
      sensitive than SRAR in detecting DSP, it does not provide additional diagnostic
      yield to the assessment of MP NCS alone in diabetic DSP patients with normal
      sural responses.

PMID- 27043974
TI  - Calorespirometric feeding control enhances bioproduction from toxic feedstocks
      Demonstration for biopolymer production out of methanol.
AB  - The sustainable production of fuels and industrial bulk chemicals by
      microorganisms in biotechnological processes is promising but still facing
      various challenges. In particular, toxic substrates require an efficient process
      control strategy. Methanol, as an example, has the potential to become a major
      future feedstock due to its availability from fossil and renewable resources.
      However, besides being toxic, methanol is highly volatile. To optimize its dosage
      during microbial cultivations, an innovative, predictive process control strategy
      based on calorespirometry, i.e., simultaneous measurements of heat and CO2
      emission rates, was developed. This rarely used technique allows an online
      estimation of growth parameters such as the specific growth rate and substrate
      consumption rate as well as a detection of shifts in microbial metabolism thus
      enabling an adapted feeding for different phases of growth. The calorespirometric
      control strategy is demonstrated exemplarily for growth of the methylotrophic
      bacterium Methylobacterium extorquens on methanol and compared to alternative
      control strategies. Applying the new approach, the methanol concentration could
      be maintained far below a critical limit, while increased growth rates of M.
      extorquens and higher final contents of the biopolymer polyhydroxybutyrate were
      obtained. Biotechnol. Bioeng. 2016;113: 2113-2121. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27043975
TI  - New perspectives on the role of cardiac magnetic resonance imaging to evaluate
      myocardial salvage and myocardial hemorrhage after acute reperfused ST-elevation
      myocardial infarction.
AB  - Cardiac magnetic resonance (CMR) imaging enables the assessment of left
      ventricular function and pathology. In addition to established contrast-enhanced
      methods for the assessment of infarct size and microvascular obstruction, other
      infarct pathologies, such as myocardial edema and myocardial hemorrhage, can be
      identified using innovative CMR techniques. The initial extent of myocardial
      edema revealed by T2-weighted CMR has to be stable for edema to be taken as a
      retrospective marker of the area-at-risk, which is used to calculate myocardial
      salvage. The timing of edema assessment is important and should be focused within
      2 - 7 days post-reperfusion. Some recent investigations have called into question
      the diagnostic validity of edema imaging after acute STEMI. Considering the
      results of these studies, as well as results from our own laboratory, we conclude
      that the time-course of edema post-STEMI is unimodal, not bimodal. Myocardial
      hemorrhage is the final consequence of severe vascular injury and a progressive
      and prognostically important complication early post-MI. Myocardial hemorrhage is
      a therapeutic target to limit reperfusion injury and infarct size post-STEMI. 

PMID- 27043976
TI  - Marketing and the Most Trusted Profession: The Invisible Interactions Between
      Registered Nurses and Industry.
AB  - BACKGROUND: The mainstay for addressing conflicts of interest in health care is
      disclosure of personal financial ties to industry. However, this approach fails
      to capture the complexity of industry interactions that are built into clinical
      practice. Further, the policy climate focuses on physicians and traditional
      pharmaceutical marketing. OBJECTIVE: To describe industry activities targeted at
      registered nurses. DESIGN: Qualitative, ethnographic study conducted from January
      2012 to October 2014. SETTING: Four acute care hospitals in a western U.S. city.
      PARTICIPANTS: A purposive sample of 72 participants with direct experience with
      industry, including staff nurses, administrators, and industry and supply chain
      professionals. MEASUREMENTS: Fieldwork, including observations (102 hours),
      semistructured in-depth interviews (n = 51), focus groups (n = 4), and documents
      analysis. RESULTS: Nurses' reported financial relationships with industry were
      similar to those reported by prescribers. However, nurses reported that their
      most significant interactions with industry occurred in daily practice. The
      current policy environment rendered these interactions invisible, leaving nurses
      with little guidance to ensure that the boundary between service and sales
      remained intact. LIMITATIONS: This study could not determine the frequency or
      prevalence of nurse-industry interactions. The sample is not representative.
      CONCLUSION: Nurse-industry interactions may be common and influential, but they
      remain invisible in the current policy climate. Although some aspects of these
      interactions may be beneficial, others may pose financial risks to hospitals or
      safety risks to patients. Disclosure strategies alone do not provide health
      professionals with adequate support to manage day-to-day interactions. Management
      of industry interactions must include guidance for nurses. PRIMARY FUNDING
      SOURCE: Agency for Healthcare Research and Quality; Canadian Institutes of Health
      Research; and University of California, San Francisco.

PMID- 27043977
TI  - What Children Face From the Federal Budget.

PMID- 27043978
TI  - A novel classification system for assessment of approximal caries lesion
      progression in bitewing radiographs.
AB  - OBJECTIVES: To design and pilot a novel classification system for the assessment
      of caries lesion progression in bitewing radiography and to report rater
      agreement of the system. METHODS: A classification system with drawings and text
      was designed to assess caries lesion progression. Guidelines for Reporting
      Reliability and Agreement Studies were used to study and report rater agreement.
      Pairs of posterior bitewing radiographs (baseline and 1-year follow-up) with
      different status concerning caries lesion progression were selected from files
      from public dental health clinics. 10 raters, 5 general dental practitioners and
      5 specialists in oral and maxillofacial radiology were asked to assess the
      radiographs with the aid of the classification system. Seven raters repeated
      their assessments. Rater agreement was expressed as percentage of agreement and
      kappa. RESULTS: Kappa for the interrater agreement of 10 raters assessing
      progression was 0.61, indicating substantial agreement. Agreement was moderate
      for progression in the outer half of the dentine (kappa 0.55) and within enamel
      (kappa 0.44). Pairwise interrater agreement varied (range 69-92%; kappa 0.42
      0.84). For about half of the pairs of raters, kappa was substantial (>=0.61).
      Intrarater agreement assessing progression was substantial (kappa 0.66-0.82).
      CONCLUSIONS: We demonstrated the applicability of the proposed classification
      system on caries lesion progression with respect to rater agreement. This system
      can provide a common framework for clinical decision-making on caries
      interventional methods and patient visiting intervals. Scientifically, this
      system allows for a comparative analysis of different methods of prevention and
      treatment of caries as well as of different caries risk assessment methods.

PMID- 27043979
TI  - Automated Breast Ultrasound in Breast Cancer Screening of Women With Dense
      Breasts: Reader Study of Mammography-Negative and Mammography-Positive Cancers.
AB  - OBJECTIVE: The objective of our study was to assess and compare, in a reader
      study, radiologists' performance in the detection of breast cancer using full
      field digital mammography (FFDM) alone and using FFDM with 3D automated breast
      ultrasound (ABUS). MATERIALS AND METHODS: In this multireader, multicase,
      sequential-design reader study, 17 Mammography Quality Standards Act-qualified
      radiologists interpreted a cancer-enriched set of FFDM and ABUS examinations. All
      imaging studies were of asymptomatic women with BI-RADS C or D breast density.
      Readers first interpreted FFDM alone and subsequently interpreted FFDM combined
      with ABUS. The analysis included 185 cases: 133 noncancers and 52 biopsy-proven
      cancers. Of the 52 cancer cases, the screening FFDM images were interpreted as
      showing BI-RADS 1 or 2 findings in 31 cases and BI-RADS 0 findings in 21 cases.
      For the cases interpreted as BI-RADS 0, a forced BI-RADS score was also given.
      Reader performance was compared in terms of AUC under the ROC curve, sensitivity,
      and specificity. RESULTS: The AUC was 0.72 for FFDM alone and 0.82 for FFDM
      combined with ABUS, yielding a statistically significant 14% relative improvement
      in AUC (i.e., change in AUC = 0.10 [95% CI, 0.07-0.14]; p < 0.001). When a
      cutpoint of BI-RADS 3 was used, the sensitivity across all readers was 57.5% for
      FFDM alone and 74.1% for FFDM with ABUS, yielding a statistically significant
      increase in sensitivity (p < 0.001) (relative increase = 29%). Overall
      specificity was 78.1% for FFDM alone and 76.1% for FFDM with ABUS (p = 0.496).
      For only the mammography-negative cancers, the average AUC was 0.60 for FFDM
      alone and 0.75 for FFDM with ABUS, yielding a statistically significant 25%
      relative improvement in AUC with the addition of ABUS (p < 0.001). CONCLUSION:
      Combining mammography with ABUS, compared with mammography alone, significantly
      improved readers' detection of breast cancers in women with dense breast tissue
      without substantially affecting specificity.

PMID- 27043980
TI  - The role of the confined water in the dynamic crossover of hydrated lysozyme
      powders.
AB  - Water is of fundamental importance for life since it plays a critical role in
      biological systems. An organism can only function if its macromolecules and other
      bioactive molecules are hydrated. However, currently there is a gap in the
      understanding of how protein interfaces affect water's structure and properties.
      This work presents combined dielectric and calorimetric measurements of hydrated
      lysozyme powders with different levels of hydration in a broad temperature
      interval. We chose lysozyme as a test sample since this globular protein has a
      well-defined pore with an active hydrophilic center inside. Based on the
      dielectric and calorimetric tests it was shown that a water quasi-solution, which
      contains the protein residues, has a glass transition temperature at around 155
      +/- 3 K. The water confined in the pore of the active center of the lysozyme has
      its melting temperature at around 186 +/- 3 K. Melting of confined water is
      believed to liberate the internal motions of protein macromolecules. 

PMID- 27043981
TI  - Should We Screen for Coronary Heart Disease in Asymptomatic Persons?: Grand
      Rounds Discussion From Beth Israel Deaconess Medical Center.
AB  - In March 2015, the American College of Physicians (ACP) released a clinical
      guideline on the value of screening for coronary heart disease (CHD) in
      asymptomatic persons. The guideline authors found that results of screening
      studies are unlikely to change patient management or the intensity of risk factor
      reduction strategies. Most events occur in patients who are at low to
      intermediate risk for CHD; and in low-risk asymptomatic patients, percutaneous
      coronary intervention in "screen-positive" patients does not improve outcomes and
      creates unnecessary risks. As a result, the ACP recommended against screening for
      asymptomatic patients who are at low risk for CHD. Instead, it recommended a
      focus on proven strategies, such as treatment of hypertension and
      hypercholesterolemia, to reduce risk in appropriately selected asymptomatic
      persons. Two discussants weigh the evidence for and against screening for CHD in
      asymptomatic patients with varying degrees of risk and provide recommendations
      for a specific patient who is uncertain whether to proceed to screening. 

PMID- 27043984
TI  - The Nazi Patient.

PMID- 27043985
TI  - Management of Dyslipidemia for Cardiovascular Disease Risk Reduction.

PMID- 27043986
TI  - Management of Dyslipidemia for Cardiovascular Disease Risk Reduction.

PMID- 27043987
TI  - Cardiovascular Mortality Associated With 5 Leading Risk Factors.

PMID- 27043988
TI  - Cardiovascular Mortality Associated With 5 Leading Risk Factors.

PMID- 27043989
TI  - Prevention Strategies for Contrast-Induced Nephropathy.

PMID- 27043990
TI  - Prevention Strategies for Contrast-Induced Nephropathy.

PMID- 27043992
TI  - In the Clinic. Substance Use Disorders.
AB  - This issue provides a clinical overview of substance use disorders, focusing on
      epidemiology, prevention, diagnosis, complications, and management. The content
      of In the Clinic is drawn from the clinical information and education resources
      of the American College of Physicians (ACP), including MKSAP (Medical Knowledge
      and Self-Assessment Program). Annals of Internal Medicine editors develop In the
      Clinic in collaboration with the ACP's Medical Education and Publishing divisions
      and with the assistance of additional science writers and physician writers. 

PMID- 27043993
TI  - Web Exclusives. Annals Graphic Medicine: Please Don't Use Patient Names.

PMID- 27043994
TI  - Deciphering the Lipid Architecture of the Rat Sciatic Nerve Using Imaging Mass
      Spectrometry.
AB  - Knowledge on the normal structure and molecular composition of the peripheral
      nerves is essential to understand their pathophysiology and to select the
      regeneration strategies after injury. However, the precise lipid composition of
      the normal peripheral nerve is still poorly known. Here, we present the first
      study of distribution of individual lipids in the mature sciatic nerve of rats by
      imaging mass spectrometry. Both positive and negative ion modes were used to
      detect, identify and in situ map 166 molecular species of mainly
      glycerophospholipids, sphingomyelins, sulfatides, and diacyl and
      triacylglycerols. In parallel, lipid extracts were analyzed by LC-MS/MS to verify
      and complement the identification of lipids directly from the whole tissue. Three
      anatomical regions were clearly identified by its differential lipid composition:
      the nerve fibers, the connective tissue and the adipose tissue that surrounds the
      nerve. Unexpectedly, very little variety of phosphatidylcholine (PC) species was
      found, being by far PC 34:1 the most abundant species. Also, a rich composition
      on sulfatides was detected in fibers, probably due to the important role they
      play in the myelin cover around axons, as well as an abundance of storage lipids
      in the adipose and connective tissues. The database of lipids here presented for
      each region and for the whole sciatic nerve is a first step toward understanding
      the variety of the peripheral nerves' lipidome and its changes associated with
      different diseases and mechanical injuries.

PMID- 27043995
TI  - Implementation of a Ventilator-Associated Pneumonia Prevention Bundle in a Single
      PICU.
AB  - OBJECTIVE: Ventilator-associated pneumonia is considered the second most frequent
      infection in pediatric intensive care, and there is agreement on its association
      with higher morbidity and increased healthcare costs. The goal of this study was
      to apply a bundle for ventilator-associated pneumonia prevention as a process for
      quality improvement in the PICU of Hospital Italiano de Buenos Aires, Argentina,
      aiming to decrease baseline ventilator-associated pneumonia rate by 25% every 6
      months over a period of 2 years. DESIGN: Quasi-experimental uninterrupted time
      series. SETTING: PICU of Hospital Italiano de Buenos Aires, Argentina. PATIENTS:
      All mechanical ventilated patients admitted to the unit. INTERVENTION: It
      consisted of the implementation of an evidence-based ventilator-associated
      pneumonia prevention bundle adapted to our unit and using the plan-do-study-act
      cycle as a strategy for quality improvement. The bundle consisted of four main
      components: head of the bed raised more than 30 degrees , oral hygiene with
      chlorhexidine, a clean and dry ventilator circuit, and daily interruption of
      sedation. MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia
      prevention team meetings started in March 2012, and the ventilator-associated
      pneumonia bundle was implemented in November 2012 after it had been developed and
      made operational. Baseline ventilator-associated pneumonia rate for the 2 years
      before intervention was 6.3 episodes every 1,000 mechanical ventilation days.
      ventilator-associated pneumonia rate evolution by semester and during the 2 years
      was, respectively, 5.7, 3.2, 1.8, and 0.0 episodes every 1,000 mechanical
      ventilation days. Monthly ventilator-associated pneumonia rate time series
      summarized in a 51-point control chart showed the presence of special cause
      variability after intervention was implemented. CONCLUSIONS: The implementation
      over 2 years of a ventilator-associated pneumonia prevention bundle specifically
      adapted to our unit using quality improvement tools was associated with a
      reduction in ventilator-associated pneumonia rate of 25% every 6 months and a nil
      rate in the last semester.

PMID- 27043996
TI  - Application of Sepsis Definitions to Pediatric Patients Admitted With Suspected
      Infections in Uganda.
AB  - OBJECTIVES: Acute infectious diseases are the most common cause of under-5
      mortality. However, the hospital burden of nonneonatal pediatric sepsis has not
      previously been described in the resource poor setting. The objective of this
      study was to determine the prevalence of sepsis among children 6 months to 5
      years old admitted with proven or suspected infection and to evaluate the
      presence of sepsis as a predictive tool for mortality during admission. DESIGN:
      In this prospective cohort study, we used the pediatric International Consensus
      Conference definition of sepsis to determine the prevalence of sepsis among
      children admitted to the pediatric ward with a proven or suspected infection. The
      diagnosis of sepsis, as well as each individual component of the sepsis
      definition, was evaluated for capturing in-hospital mortality. SETTING: The
      pediatric ward of two hospitals in Mbarara, Uganda. PATIENTS: Admitted children
      between 6 months and 5 years with a confirmed or suspected infection.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One thousand three hundred
      seven (1,307) subjects with a confirmed or suspected infection were enrolled, and
      65 children died (5.0%) during their admission. One thousand one hundred twenty
      one (85.9%) met the systemic inflammatory response syndrome criteria, and
      therefore, they were defined as having sepsis. The sepsis criteria captured 61
      deaths, demonstrating a sensitivity and a specificity of 95% (95% CI, 90-100%)
      and 15% (95% CI, 13-17%), respectively. The most discriminatory individual
      component of the systemic inflammatory response syndrome criteria was the
      leukocyte count, which alone had a sensitivity of 72% and a specificity of 56%
      for the identification of mortality in hospital. CONCLUSIONS: This study is among
      the first to quantify the burden of nonneonatal pediatric sepsis in children with
      suspected infection, using the international consensus sepsis definition, in a
      typical resource-constrained setting in Africa. This definition was found to be
      highly sensitive in identifying those who died but had very low specificity as
      most children who were admitted with infections had sepsis. The systemic
      inflammatory response syndrome-based sepsis definition offers little value in
      identification of children at high risk of in-hospital mortality in this setting.

PMID- 27043997
TI  - Nutritional intake and weight z-scores in very low birth weight infants in Peru.
AB  - OBJECTIVES: To determine the actual nutritional intake of very low birth weight
      infants and their growth outcome during the first month of life. Additionally, we
      identified factors that account for a negative neonatal outcome in this
      population. METHODS: A case-series study was conducted in a tertiary hospital in
      Lima, Peru between 2011 and 2012 and the data was obtained from medical records.
      No feeding protocol was used during this study. Daily fluids, energy and protein
      intakes were documented and weekly weight z-scores were calculated. A logistic
      regression analysis was used to identify factors for an adverse outcome, defined
      as neonatal mortality or extra-uterine growth restriction, during the first 28
      days of life. RESULTS: After applying selection criteria, 76 participants were
      included. The nutritional intakes were similar to standard values seen in the
      literature, but protein intakes were suboptimal in all of the four weeks. Birth
      weight z-score was associated with an adverse outcome (p=0.035). It was
      determined that having a birth weight z-score under -1.09 predicted a negative
      outcome with an area under the curve of 96.8% [93.5%, 100%] with a 95% confidence
      interval. CONCLUSION: Protein intakes are widely deficient in the population of
      this study. Nevertheless, an adverse outcome during the neonatal period is more
      associated with a poor birth weight z-score than nutrition-related factors.

PMID- 27043998
TI  - Second generation of thiazolylmannosides, FimH antagonists for E. coli-induced
      Crohn's disease.
AB  - The anti-adhesive strategy, consisting of disrupting bacterial attachment to the
      host cells, is widely explored as an alternative to antibiotic therapies.
      Recently, thiazolylmannosides (TazMans) have been identified as strong anti
      adhesives of E. coli strains implied in the gut inflammation of patients with
      Crohn's disease. In this work, we developed a second generation of TazMans with
      improved chemical stability. The anomeric nitrogen was substituted by short
      linkers and the compounds were assessed against the bacterial adhesin FimH and
      the clinically isolated LF82 E. coli strain in four in vitro assays. The results
      obtained on the FimH adhesin alone and the whole bacteria enabled the
      identification of a candidate for further in vivo evaluations. 

PMID- 27043999
TI  - Incidence of Cataract Surgery in Patients After Percutaneous Cardiac Intervention
      in Taiwan.

PMID- 27044000
TI  - DNA repair pathways underlie a common genetic mechanism modulating onset in
      polyglutamine diseases.
AB  - OBJECTIVE: The polyglutamine diseases, including Huntington's disease (HD) and
      multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary
      neurodegenerative diseases. They are caused by expanded CAG tracts, encoding
      glutamine, in different genes. Longer CAG repeat tracts are associated with
      earlier ages at onset, but this does not account for all of the difference, and
      the existence of additional genetic modifying factors has been suggested in these
      diseases. A recent genome-wide association study (GWAS) in HD found association
      between age at onset and genetic variants in DNA repair pathways, and we
      therefore tested whether the modifying effects of variants in DNA repair genes
      have wider effects in the polyglutamine diseases. METHODS: We assembled an
      independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and
      genotyped single-nucleotide polymorphisms (SNPs) selected from the most
      significant hits in the HD study. RESULTS: In the analysis of DNA repair genes as
      a group, we found the most significant association with age at onset when
      grouping all polyglutamine diseases (HD+SCAs; p = 1.43 * 10(-5) ). In individual
      SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs
      (p = 1.52 * 10(-5) ) and all SCAs (p = 2.22 * 10(-4) ) and rs1805323 in PMS2 with
      HD+SCAs (p = 3.14 * 10(-5) ), all in the same direction as in the HD GWAS.
      INTERPRETATION: We show that DNA repair genes significantly modify age at onset
      in HD and SCAs, suggesting a common pathogenic mechanism, which could operate
      through the observed somatic expansion of repeats that can be modulated by
      genetic manipulation of DNA repair in disease models. This offers novel
      therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983-990.

PMID- 27044001
TI  - An Efficient Supervised Training Algorithm for Multilayer Spiking Neural
      Networks.
AB  - The spiking neural networks (SNNs) are the third generation of neural networks
      and perform remarkably well in cognitive tasks such as pattern recognition. The
      spike emitting and information processing mechanisms found in biological
      cognitive systems motivate the application of the hierarchical structure and
      temporal encoding mechanism in spiking neural networks, which have exhibited
      strong computational capability. However, the hierarchical structure and temporal
      encoding approach require neurons to process information serially in space and
      time respectively, which reduce the training efficiency significantly. For
      training the hierarchical SNNs, most existing methods are based on the
      traditional back-propagation algorithm, inheriting its drawbacks of the gradient
      diffusion and the sensitivity on parameters. To keep the powerful computation
      capability of the hierarchical structure and temporal encoding mechanism, but to
      overcome the low efficiency of the existing algorithms, a new training algorithm,
      the Normalized Spiking Error Back Propagation (NSEBP) is proposed in this paper.
      In the feedforward calculation, the output spike times are calculated by solving
      the quadratic function in the spike response model instead of detecting
      postsynaptic voltage states at all time points in traditional algorithms.
      Besides, in the feedback weight modification, the computational error is
      propagated to previous layers by the presynaptic spike jitter instead of the
      gradient decent rule, which realizes the layer-wised training. Furthermore, our
      algorithm investigates the mathematical relation between the weight variation and
      voltage error change, which makes the normalization in the weight modification
      applicable. Adopting these strategies, our algorithm outperforms the traditional
      SNN multi-layer algorithms in terms of learning efficiency and parameter
      sensitivity, that are also demonstrated by the comprehensive experimental results
      in this paper. 

PMID- 27044002
TI  - In utero Programming of Allergic Susceptibility.
AB  - BACKGROUND: Around 30-40% of the world's population will experience allergy, the
      most common and earliest-onset noncommunicable disease. With a steady rise in the
      incidence of allergic disease over recent decades, up to 18% of children will
      suffer a respiratory, food or skin allergy before their 18th birthday. There is
      compelling evidence that the risk of developing allergy is influenced by early
      life events and particularly in utero exposures. METHODS: A comprehensive
      literature review was undertaken which outlines prenatal risk factors and
      potential mechanisms underlying the development of allergy in childhood. RESULTS:
      Exposures including maternal cigarette smoking, preterm birth and Caesarean
      delivery are implicated in predisposing infants to the later development of
      allergy. In contrast, restricted growth in utero, a healthy maternal diet and a
      larger family size are protective, but the mechanisms here are unclear and
      require further investigation. CONCLUSION: To ameliorate the allergy pandemic in
      young children, we must define prenatal mechanisms that alter the programming of
      the fetal immune system and also identify specific targets for antenatal
      interventions.

PMID- 27044003
TI  - Embryo-Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits.
AB  - Pregabalin was evaluated for potential developmental toxicity in mice and
      rabbits. Pregabalin was administered once daily by oral gavage to female albino
      mice (500, 1250, or 2500 mg/kg) and New Zealand White rabbits (250, 500, or 1250
      mg/kg) during organogenesis (gestation day 6 through 15 [mice] or 6 through 20
      [rabbits]). Fetuses were evaluated for viability, growth, and morphological
      development. Pregabalin administration to mice did not induce maternal or
      developmental toxicity at doses up to 2500 mg/kg, which was associated with a
      maternal plasma exposure (AUC0-24 ) of 3790 MUg*hr/ml, >=30 times the expected
      human exposure at the maximum recommended daily dose (MRD; 600 mg/day). In
      rabbits, treatment-related clinical signs occurred at all doses (AUC0-24 of 1397,
      2023, and 4803 MUg*hr/ml at 250, 500, and 1250 mg/kg, respectively). Maternal
      toxicity was evident at all doses and included ataxia, hypoactivity, and cool to
      touch. In addition, abortion and females euthanized moribund with total
      resorption occurred at 1250 mg/kg. There were no treatment-related malformations
      at any dose. At 1250 mg/kg, compared with study and historical controls, the
      percentage of fetuses with retarded ossification was significantly increased and
      the mean number of ossification sites was decreased, which correlated with
      decreased fetal and placental weights, consistent with in utero growth
      retardation. Therefore, the no-effect dose for developmental toxicity in rabbits
      was 500 mg/kg, which produced systemic exposure approximately 16-times human
      exposure at the MRD. These findings indicate that pregabalin, at the highest dose
      tested, was not teratogenic in mice or rabbits. 

PMID- 27044004
TI  - Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on
      steroid formation.
AB  - Endocrine disruptors (ED) are environmental pollutants that mimic endogenous
      hormonal signals. Exposure to EDs during fetal and early life is a public health
      concern because these are periods characterized by high cellular plasticity that
      influence the physiology and development of disease later in life. Phthalates are
      plasticizers used in the industry to manufacture polyvinyl chloride products and
      several consumer products. Di(2-ethylhexyl) phthalate (DEHP) is one of the most
      produced plasticizers; it is ubiquitously found contaminating the environment,
      and has been shown to be an ED. Human exposure to phthalates starts during fetal
      development and continues after birth through contact of the newborn with the
      environment and contaminated food sources. We used a rat model in which pregnant
      dams are gavaged with DEHP from gestational day 14 until birth to study the long
      term effects of DEHP. This window of fetal exposure results in decreased
      circulating testosterone and aldosterone levels in adult male offspring and
      estradiol in the female. The observed steroid changes are likely of an epigenetic
      origin as DEHP is rapidly cleared after birth. Here, we review the long-term
      effects of fetal exposure to DEHP with a focus on the molecular and epigenetic
      changes, including DNA methylation, which may mediate long-term endocrine
      dysfunction.

PMID- 27044005
TI  - Association of impaired renal function and poor prognosis in oropharyngeal
      squamous cell carcinoma.
AB  - BACKGROUND: Renal function influences decisions regarding treatment for patients
      with oropharyngeal squamous cell carcinoma (SCC). However, the importance of
      renal function in oropharyngeal SCC has not yet been reported. METHODS: Four
      hundred sixty patients with oropharyngeal SCC treated with curative intent
      between April 2005 and March 2007 in 12 institutions in Japan were analyzed
      retrospectively. RESULTS: Four hundred three patients (87.6%) showed a creatinine
      clearance (CrCl) >=50 mL/min and 57 (12.4%) with a CrCl <50 mL/min. Age was
      associated with worse overall survival (OS), whereas stage IVB, radiotherapy
      (RT), and CrCl <50 were associated with worse OS on univariate analyses. Surgery
      and hypertension were associated with better OS on univariate analyses. On
      multivariate analysis, age, stage, hypertension, and CrCl were also found to be
      significantly associated with OS. CONCLUSION: Based on this retrospective study,
      impaired renal function is an independent predictor of increased risk of death in
      patients with oropharyngeal SCC. (c) 2016 Wiley Periodicals, Inc. Head Neck 38:
      First-1500, 2016.

PMID- 27044006
TI  - 'I Know that I Do Have HIV but Nobody Saw Me': Oral HIV Self-Testing in an
      Informal Settlement in South Africa.
AB  - Reaching universal HIV-status awareness is crucial to ensure all HIV-infected
      patients access antiretroviral treatment (ART) and achieve virological
      suppression. Opportunities for HIV testing could be enhanced by offering self
      testing in populations that fear stigma and discrimination when accessing
      conventional HIV Counselling and Testing (HCT) in health care facilities. This
      qualitative research aims to examine the feasibility and acceptability of
      unsupervised oral self-testing for home use in an informal settlement of South
      Africa. Eleven in-depth interviews, two couple interviews, and two focus group
      discussions were conducted with seven healthcare workers and thirteen community
      members. Thematic analysis was done concurrently with data collection.
      Acceptability to offer home self-testing was demonstrated in this research. Home
      self-testing might help this population overcome barriers to accepting HCT; this
      was particularly expressed in the male and youth groups. Nevertheless, pilot
      interventions must provide evidence of potential harm related to home self
      testing, intensify efforts to offer quality counselling, and ensure linkage to
      HIV/ART-care following a positive self-test result. 

PMID- 27044007
TI  - Quantitative maternal hepatitis B surface antigen predicts maternally transmitted
      hepatitis B virus infection.
AB  - : Despite immunoprophylaxis, hepatitis B virus (HBV) transmission in highly
      viremic mothers remains a global health issue. Using quantitative maternal
      surface antigen (HBsAg) to predict HBV infection in infants has not been
      investigated. We enrolled 526 mother-infant pairs with positive maternal HBsAg
      under current immunoprophylaxis. Maternal viral load and quantitative HBsAg were
      measured in the peripartum period. Infant HBsAg seropositivity for more than 6
      months was defined as chronic infection. Rates of chronic infection in infants at
      various maternal HBsAg levels were estimated using a multivariate logistic
      regression model. Results showed that maternal HBsAg was positively correlated
      with maternal viral load (r = 0.69; P < 0.001) and accurately predicted maternal
      viral load above 6, 7, and 8 log10 IU/mL with an area under the receiver
      operating characteristic curve (AUC) of 0.97, 0.98, and 0.95. Nineteen infants
      were chronically infected. After adjustment for the other risk factor, maternal
      HBsAg level was significantly associated with risk of infection (adjusted odds
      ratio for each log10 IU/mL increase, 15.02; 95% confidence interval [CI], 3.89
      57.94; P < 0.001). The AUC for predicting infection by quantitative maternal
      HBsAg was comparable to that by maternal viral load (0.89 vs. 0.87; P = 0.459).
      Estimated rates of infection at maternal HBsAg levels of 4, 4.5, and 5 log10
      IU/mL were 2.4% (95% CI, 0.1-4.6; P = 0.04), 8.6% (95% CI, 4.5-12.7; P < 0.001),
      and 26.4% (95% CI, 12.6-40.2; P < 0.001). CONCLUSION: Quantitative maternal HBsAg
      predicts infection in infants as well as maternal viral load does. Antiviral
      therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10
      IU/mL to interrupt mother-to-infant transmission. (Hepatology 2016;64:1451-1461).

PMID- 27044008
TI  - Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine
      Administered Patients.
AB  - The negative symptoms of schizophrenia (SZ) are associated with a pattern of
      reinforcement learning (RL) deficits likely related to degraded representations
      of reward values. However, the RL tasks used to date have required active
      responses to both reward and punishing stimuli. Pavlovian biases have been shown
      to affect performance on these tasks through invigoration of action to reward and
      inhibition of action to punishment, and may be partially responsible for the
      effects found in patients. Forty-five patients with schizophrenia and 30
      demographically-matched controls completed a four-stimulus reinforcement learning
      task that crossed action ("Go" or "NoGo") and the valence of the optimal outcome
      (reward or punishment-avoidance), such that all combinations of action and
      outcome valence were tested. Behaviour was modelled using a six-parameter RL
      model and EEG was simultaneously recorded. Patients demonstrated a reduction in
      Pavlovian performance bias that was evident in a reduced Go bias across the full
      group. In a subset of patients administered clozapine, the reduction in Pavlovian
      bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied
      by feedback processing differences at the time of the P3a component. The reduced
      Pavlovian bias in patients is suggested to be due to reduced fidelity in the
      communication between striatal regions and frontal cortex. It may also partially
      account for previous findings of poorer "Go-learning" in schizophrenia where "Go"
      responses or Pavlovian consistent responses are required for optimal performance.
      An attenuated P3a component dynamic in patients is consistent with a view that
      deficits in operant learning are due to impairments in adaptively using feedback
      to update representations of stimulus value. 

PMID- 27044009
TI  - Benign Paroxysmal Positional Vertigo after Dental Procedures: A Population-Based
      Case-Control Study.
AB  - BACKGROUND: Benign paroxysmal positional vertigo (BPPV), the most common type of
      vertigo in the general population, is thought to be caused by dislodgement of
      otoliths from otolithic organs into the semicircular canals. In most cases,
      however, the cause behind the otolith dislodgement is unknown. Dental procedures,
      one of the most common medical treatments, are considered to be a possible cause
      of BPPV, although this has yet to be proven. This study is the first nationwide
      population-based case-control study conducted to investigate the correlation
      between BPPV and dental manipulation. METHODS: Patients diagnosed with BPPV
      between January 1, 2007 and December 31, 2012 were recruited from the National
      Health Insurance Research Database in Taiwan. We further identified those who had
      undergone dental procedures within 1 month and within 3 months before the first
      diagnosis date of BPPV. We also identified the comorbidities of the patients with
      BPPV, including head trauma, osteoporosis, migraine, hypertension, diabetes,
      hyperlipidemia and stroke. These variables were then compared to those in age-
      and gender-matched controls. RESULTS: In total, 768 patients with BPPV and 1536
      age- and gender-matched controls were recruited. In the BPPV group, 9.2% of the
      patients had undergone dental procedures within 1 month before the diagnosis of
      BPPV. In contrast, only 5.5% of the controls had undergone dental treatment
      within 1 month before the date at which they were identified (P = 0.001). After
      adjustments for demographic factors and comorbidities, recent exposure to dental
      procedures was positively associated with BPPV (adjusted odds ratio 1.77; 95%
      confidence interval 1.27-2.47). This association was still significant if we
      expanded the time period from 1 month to 3 months (adjusted odds ratio 1.77; 95%
      confidence interval 1.39-2.26). CONCLUSIONS: Our results demonstrated a
      correlation between dental procedures and BPPV. The specialists who treat
      patients with BPPV should consider dental procedures to be a risk factor, and
      dentists should recognize BPPV as a possible complication of dental treatment.

PMID- 27044010
TI  - The Role of Physical Activity in Harm Reduction among Betel Quid Chewers from a
      Prospective Cohort of 419,378 Individuals.
AB  - OBJECTIVE: To assess the benefits of regular exercise in reducing harms
      associated with betel quid (BQ) chewing. METHODS: The study cohort, 419,378
      individuals, participated in a medical screening program between 1994 and 2008,
      with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day.
      Physical activity of each individual, based on "MET-hour/week", was classified as
      "inactive" or "active", where activity started from a daily 15 minutes/day or
      more of brisk walking (>=3.75 MET-hour/week). Hazard ratios for mortality and
      remaining years in life expectancy were calculated. RESULTS: Nearly one fifth
      (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold
      increase in oral cancer risk; and a 2-3-fold increase in mortality from lung,
      esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling
      of all-cause mortality. More than half of chewers were physically inactive (59%).
      Physical activity was beneficial for chewers, with a reduction of all-cause
      mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years,
      compared to non-chewers, but being active, chewers improved their health by
      gaining 2.5 years. The improvement, however, fell short of offsetting the harms
      from chewing. CONCLUSIONS: Chewers had serious health consequences, but being
      physically active, chewers could mitigate some of these adverse effects, and
      extend life expectancy by 2.5 years and reduce mortality by one fifth.
      Encouraging exercise, in addition to quitting chewing, remains the best advice
      for 1.5 million chewers in Taiwan.

PMID- 27044011
TI  - Determination of liver and muscle aflatoxin B1 residues and select serum
      chemistry variables during chronic aflatoxicosis in broiler chickens.
AB  - BACKGROUND: Aflatoxins are secondary metabolites of the fungus Aspergillus sp.
      The presence of aflatoxin in poultry feeds results in direct toxicity and
      economic losses, and human health hazards after consumption of contaminated liver
      and meat. OBJECTIVES: The study was conducted to assess tissue residues of
      aflatoxin B1 (AFB1), and alterations in select clinical chemistry variables in
      serum during chronic aflatoxicosis in broiler chicks fed different dietary levels
      of AFB1. MATERIALS AND METHODS: Six groups of broiler chickens were fed diets
      containing between 0 and 800 ppb of AFB1 for 28 days. Groups of birds were
      terminated on days 0, 5, 13, 15, 20, and 28, and AFB1 levels were determined by
      HPLC in liver and muscle. Serum activities of ALT and ALP, and total protein and
      albumin concentrations were determined. RESULTS: No AFB1 residues were detected
      in liver after 50 ppb AFB1, and muscle after 50 and 100 ppb AFB1 feeding.
      Residues above the permissible threshold (> 2.0 ng/g) were only detected in liver
      tissues of groups fed 400 ppb and 800 ppb AFB1 in feed. The ALT and ALP
      activities in treated groups were significantly higher, and total protein and
      albumin concentrations were significantly lower in all treated groups compared to
      controls. CONCLUSIONS: Continuous feeding of AFB1 to broiler chicken at levels of
      50 and 100 ppb for 28 days did not reveal measurable AFB1 residues in muscle
      tissues. Serum values of ALT, ALP, total protein, and albumin may serve as
      markers for chronic aflatoxicosis in affected poultry.

PMID- 27044012
TI  - Exploring membrane respiratory chains.
AB  - Acquisition of energy is central to life. In addition to the synthesis of ATP,
      organisms need energy for the establishment and maintenance of a transmembrane
      difference in electrochemical potential, in order to import and export
      metabolites or to their motility. The membrane potential is established by a
      variety of membrane bound respiratory complexes. In this work we explored the
      diversity of membrane respiratory chains and the presence of the different enzyme
      complexes in the several phyla of life. We performed taxonomic profiles of the
      several membrane bound respiratory proteins and complexes evaluating the presence
      of their respective coding genes in all species deposited in KEGG database. We
      evaluated 26 quinone reductases, 5 quinol:electron carriers oxidoreductases and
      18 terminal electron acceptor reductases. We further included in the analyses
      enzymes performing redox or decarboxylation driven ion translocation, ATP
      synthase and transhydrogenase and we also investigated the electron carriers that
      perform functional connection between the membrane complexes, quinones or soluble
      proteins. Our results bring a novel, broad and integrated perspective of membrane
      bound respiratory complexes and thus of the several energetic metabolisms of
      living systems. This article is part of a Special Issue entitled 'EBEC 2016: 19th
      European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited
      by Prof. Paolo Bernardi. 

PMID- 27044013
TI  - Genetic, Ecological and Morphological Distinctness of the Blue Mussels Mytilus
      trossulus Gould and M. edulis L. in the White Sea.
AB  - Two blue mussel lineages of Pliocene origin, Mytilus edulis (ME) and M. trossulus
      (MT), co-occur and hybridize in several regions on the shores of the North
      Atlantic. The two species were distinguished from each other by molecular methods
      in the 1980s, and a large amount of comparative data on them has been accumulated
      since that time. However, while ME and MT are now routinely distinguished by
      various genetic markers, they tend to be overlooked in ecological studies since
      morphological characters for taxonomic identification have been lacking, and no
      consistent habitat differences between lineages have been reported. Surveying a
      recently discovered area of ME and MT co-occurrence in the White Sea and
      employing a set of allozyme markers for identification, we address the issue
      whether ME and MT are true biological species with distinct ecological
      characteristics or just virtual genetic entities with no matching morphological
      and ecological identities. We find that: (1) in the White Sea, the occurrence of
      MT is largely concentrated in harbors, in line with observations from other
      subarctic regions of Europe; (2) mixed populations of ME and MT are always
      dominated by purebred individuals, animals classified as hybrids constituting
      only ca. 18%; (3) in terms of shell morphology, 80% of MT bear a distinct
      uninterrupted dark prismatic strip under the ligament while 97% of ME lack this
      character; (4) at sites of sympatry MT is more common on algal substrates while
      ME mostly lives directly on the bottom. This segregation by the substrate may
      contribute to maintaining reproductive isolation and decreasing competition
      between taxa. We conclude that while ME and MT are not fully reproductively
      isolated, they do represent clearly distinguishable biological, ecological and
      morphological entities in the White Sea. It remains to be documented whether the
      observed morphological and ecological differences are of a local character, or
      whether they have simply been overlooked in other contact zones. 

PMID- 27044014
TI  - Diplopia as a sequel of unilateral neck dissection.
AB  - BACKGROUND: The purpose of this study was to discuss the underlying etiology of
      raised intracranial pressure and its sequel after unilateral internal jugular
      vein ligation. In addition, the management protocol for such rare cases has been
      discussed along with literature review. METHODS: PubMed and Google were used to
      search the literature for cases of raised intracranial pressure with
      complications after unilateral internal jugular vein (IJV) ligation. Twelve case
      reports with 17 patients were identified. RESULTS: There were 13 male and 4
      female patients ranging between the ages of 26 and 61 years. Headache (n = 12/17;
      70.5%), diplopia (n = 10/17; 58.8%), impaired vision (n = 9/17; 52.9%), and
      aplasia or hypoplasia of the transverse sinus were seen in these patients.
      CONCLUSION: Although very rare, this potential complication after unilateral IJV
      ligation should be kept in mind. Magnetic resonance venogram (MRV) is the
      investigation of choice to ascertain the underlying etiology. Conservative
      management should be started immediately. Surgical options are reserved for
      patients with progressive symptoms. (c) 2016 Wiley Periodicals, Inc. Head Neck,
      2016 (c) 2016 Wiley Periodicals, Inc. Head Neck 38:E2475-E2478, 2016.

PMID- 27044015
TI  - Glyphosate Inhibits PPAR Gamma Induction and Differentiation of Preadipocytes and
      is able to Induce Oxidative Stress.
AB  - Glyphosate-based herbicides (GF) are extensively used for weed control. Thus, it
      is important to investigate their putative toxic effects. We have reported that
      GF at subagriculture concentrations inhibits proliferation and differentiation to
      adipocytes of 3T3-L1 fibroblasts. In this investigation, we evaluated the effect
      of GF on genes upregulated during adipogenesis. GF was able to inhibit the
      induction of PPAR gamma, the master gene in adipogenesis but not C/EBP beta,
      which precedes PPAR gamma activation. GF also inhibited differentiation and
      proliferation of another model of preadipocyte: mouse embryonic fibroblasts. In
      exponentially growing 3T3-L1 cells, GF increased lipid peroxidation and the
      activity of the antioxidant enzyme, superoxide dismutase. We also found that
      proliferation was inhibited with lower concentrations of GF when time of exposure
      was extended. Thus, GF was able to inhibit proliferation and differentiation of
      preadipocytes and to induce oxidative stress, which is indicative of its ability
      to alter cellular physiology. 

PMID- 27044016
TI  - Beneficial Effects of Anti-Interleukin-6 Antibodies on Impaired Gastrointestinal
      Motility, Inflammation and Increased Colonic Permeability in a Murine Model of
      Sepsis Are Most Pronounced When Administered in a Preventive Setup.
AB  - BACKGROUND AND OBJECTIVES: During sepsis, gastrointestinal ileus, mucosal barrier
      dysfunction and bacterial translocation are accepted to be important triggers
      that can maintain or exacerbate the septic state. In the caecal ligation and
      puncture animal model of sepsis, we demonstrated that systemic and colonic
      interleukin-6 levels are significantly increased coinciding with an impaired
      colonic barrier function. We therefore aimed to study the effect of therapeutic
      or curative administration of anti-IL6 antibodies on overall GI motility, colonic
      permeability and translocation of intestinal bacteria in blood and mesenteric
      lymph nodes in the mouse caecal ligation and puncture model. METHODS: OF-1 mice
      were randomized to either the preventive or curative protocol, in which they
      received 1 mg/kg of antibodies to interleukin-6, or its IgG isotype control
      solution. They subsequently underwent either the caecal ligation and puncture
      procedure, or sham-surgery. GI motility was assessed 48 h following the
      procedure, as well as colonic permeability, serum and colon cytokines, colonic
      tight junction proteins at the mRNA level; cultures of blood and mesenteric lymph
      nodes were performed. RESULTS: Preventive administration of anti-interleukin-6
      antibodies successfully counteracted the gastrointestinal motility disturbances
      and impaired colonic barrier function that could be observed in vehicle-treated
      septic animals. Serum and colonic levels of proinflammatory cytokines were
      significantly lower when animals were preventively treated with anti-interleukin
      6 antibodies. A repetitive injection 24 h later resulted in the most pronounced
      effects. Curative treatment significantly lowered systemic and colonic
      inflammation markers while the effects on transit and permeability were
      unfortunately no longer significant. CONCLUSIONS: Caecal ligation and puncture
      resulted in septic ileus with an increased colonic permeability. Antibodies to
      interleukin-6 were able to ameliorate gastro-intestinal motility, suppress
      inflammation and normalize the permeability of the colonic wall, with the
      preventive administration combined with a repeat injection being far more
      efficacious than the sole preventive or curative one.

PMID- 27044017
TI  - Effects of an Interactive School-Based Program for Preventing Adolescent Sexual
      Harassment: A Cluster-Randomized Controlled Evaluation Study.
AB  - Many adolescents experience sexual harassment and victims of sexual harassment
      have higher risks regarding well-being and health behaviors such as higher risks
      of suicidal thoughts, suicidal ideation and feeling unsafe at school. A peer
      performed play and school lessons on preventing sexual harassment behavior were
      presented to secondary school students. We evaluated its effectiveness, using a
      cluster-randomized controlled design to assign schools to an experimental
      condition [n = 14 schools; 431 students (51 % female)] and a control condition [n
      = 11 schools; 384 students (51 % female)]. To measure the effects of the
      intervention at first post-test and 6-month follow-up, our multilevel analyses
      used a two-level random intercept model. Outcome measures were sexual harassment
      behaviors, behavioral determinants and distal factors influencing these
      behaviors. At post-test, students in the experimental group reported a reduced
      intention to commit sexual harassment behavior and higher self-efficacy in
      rejecting it. At post-test and follow-up there was a significant positive effect
      on social norms for rejecting sexual harassment behavior. At follow-up, sexual
      self-esteem was higher in students in the experimental group than in the control
      group. Effects on these determinants will benefit adolescents' future sexual
      behaviors. In combination, the play and lessons, possibly together with continued
      sexual health education and skills programs on social-emotional learning in
      subsequent school years, have potential for preventing sexual harassment
      behavior.

PMID- 27044018
TI  - Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via
      inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy.
AB  - Cellular therapy with mesenchymal stem cells (MSCs) protects cortical neurons
      against hypoxic-ischemic injury of stroke. Although sorts of efforts have been
      made to confirm the neuroprotective effect of MSCs on neurons against hypoxic
      ischemic injury, the mechanism is until now far away from clear. Here in this
      study, oxygen-glucose deprivation (OGD)-injured neuron model was applied to mimic
      the neuronal hypoxic-ischemic injury in vitro. Co-culturing with MSCs in a
      transwell co-culture system, the OGD injured neurons were rescued by 75.0 %.
      Further data demonstrated that co-culturing with MSCs protected the cortical
      neurons from the OGD-induced parthanatos by alleviating apoptosis-inducing factor
      (AIF) nuclear translocation; attenuated the neuronal necroptosis by down
      regulating the expression of the two essential kinases in necroptosis, receptor
      interacting protein kinase1 (RIP1) and 3 (RIP3); rescued the neurons from
      apoptosis by deactivating caspase-3; whilst performed no significant influence on
      OGD-induced neuronal autophagy, according to its failed regulation on Beclin1. In
      conclusion, MSCs potentially protect the cortical neurons from OGD-injury in
      vitro, through rescuing neurons from the cell death of parthanatos, necroptosis,
      and apoptosis, but not autophagy, which could provide some evidence to the
      mechanism explanation on stem cell treatment for ischemic stroke.

PMID- 27044019
TI  - Low occurrence of the new species Staphylococcus argenteus in a Staphylococcus
      aureus collection of human isolates from Belgium.
AB  - Staphylococcus argenteus is a novel Staphylococcus species closely related to
      Staphylococcus aureus that has been recently described. In this study, we
      investigated the proportion and the characteristics of S. argenteus recovered
      from humans in Belgium. S. aureus. human isolates collected in Belgium from 2006
      to 2015 (n = 1,903) were retrospectively characterised via the presence of non
      pigmented colonies on chocolate agar, spa typing and rpoB sequencing to determine
      if some of them were in fact S. argenteus. Out of 73 strains non-pigmented on
      chocolate plates, 3 isolates (0.16 %) showed rpoB sequences, in addition to spa
      and sequence types (ST2250/t5787, ST2250/t6675, ST3240/t6675), related to S.
      argenteus. Two of them were methicillin-resistant, harbouring a SCCmec type IV.
      The three S. argenteus isolates carried genes (sak, scn) of the immune evasion
      cluster. This first Belgian nationwide analysis showed a low occurrence of S.
      argenteus. Further studies should be conducted to identify the distribution range
      and the clinical impact of this new species. 

PMID- 27044020
TI  - Adult Spinal Deformity Correction with Multi-level Anterior Column Releases:
      Description of a New Surgical Technique and Literature Review.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To evaluate radiographic and clinical
      outcomes of adults with spinal deformity treated with multilevel anterior column
      releases (ACR). SUMMARY OF BACKGROUND DATA: Pedicle subtraction osteotomy can be
      used effectively to correct spinal deformity; however, it is not without
      complications. ACR is an attractive alternative minimally invasive technique for
      spinal deformity correction, although few clinical reports on its clinical
      effectiveness exist. METHODS: Adults with spinal deformity who underwent
      multilevel ACRs (>=2) followed by open posterior instrumentation with a minimum 1
      year follow-up were retrospectively reviewed. Deformity radiographic data and
      clinical outcomes, including the Oswestry Disability Index (ODI) and the EuroQol
      5D were analyzed. RESULTS: Eight patients [7 female, 1 male; mean age 65 y (49-79
      y)] met inclusion criteria. The mean follow-up was 18.4 months (12-28 mo). The
      average number of levels treated with an ACR per patient was 2.4 (2-3). There
      were no anterior approach-related complications. The average number of levels
      instrumented posteriorly was 8.1 (3-15). Six patients underwent Schwab type 1
      posterior osteotomies (partial facetectomies). After the first anterior stage,
      there was a significant increase in the lumbar lordosis and significant decreases
      in the sagittal vertical axis, pelvic tilt, and lumbopelvic mismatch (P<0.05).
      After the second stage there was no significant change in the sagittal vertical
      axis, lumbar lordosis, pelvic tilt, or lumbopelvic mismatch relative to the
      values obtained after ACR. There was significantly less disability
      postoperatively [ODI: 15 (0-30)] compared with preoperatively [ODI: 46 (16-80)]
      (P<0.01). There was significant improvement in general health after operation, as
      assessed by the EuroQol-5D utility scores [preop: 0.44 (0.21-0.82) vs. postop:
      0.71 (0.60-0.80)] (P=0.01). Back and leg visual analog scale pain scores improved
      significantly postoperatively. CONCLUSIONS: A staged approach using multilevel
      ACRs with open posterior instrumentation has an acceptable complication profile
      and provides excellent restoration of sagittal and coronal balance and pelvic
      parameters in adults with spinal deformity.

PMID- 27044021
TI  - Psychological Distress, Interpersonal Closeness and Discrimination following the
      Charlie Hebdo Attacks.

PMID- 27044022
TI  - Patient and Physician Perceptions of Changes in Surgical Care in Mongolia 9 Years
      After Roll-out of a National Training Program for Laparoscopy.
AB  - INTRODUCTION: In 2005, the general population of Mongolia was not aware of
      laparoscopic surgery and was skeptical about the safety of surgical care. A 9
      year initiative to expand laparoscopic surgery was initiated by Mongolian
      surgeons. This study examines the current barriers to and perceptions of surgical
      care following laparoscopic surgical expansion countrywide. MATERIALS AND
      METHODS: In September 2013, interviews were conducted with 71 patients, and 39
      physicians in Mongolia. Patients and physicians were interviewed using separate
      sets of interview questions. Questions were designed to gauge perceptions of
      surgical care in Mongolia evaluating for access, affordability, sustainability,
      barriers to care, quality, and knowledge of laparoscopy. Responses were fine
      coded for statistical analysis. RESULTS: 79 % of patients felt surgical care was
      improving in Mongolia, and 76 % would choose laparoscopy if available. Physicians
      (100 %) felt laparoscopic surgery had improved surgical care in Mongolia.
      Barriers to care for patients were time to work up and diagnosis (37 %), and
      funding an operation (39 %). None of the 36 % of patients who stated funding an
      operation would be difficult identified government sources of funding (p <
      0.001). Physicians identified insufficient equipment supply (69 %), insufficient
      training (41 %), and cost (38 %) as barriers for laparoscopy. 74 % of physicians
      felt that Mongolian physicians return or stay in Mongolia after training, defying
      the trend of migration in low-resource settings. DISCUSSION: Improved local
      patient and physician perception of laparoscopy is propelling the expansion of
      laparoscopy in Mongolia.

PMID- 27044023
TI  - Asian consensus statements on endoscopic management of walled-off necrosis Part
      1: Epidemiology, diagnosis, and treatment.
AB  - Walled-off necrosis (WON) is a relatively new term for encapsulated necrotic
      tissue after severe acute pancreatitis. Various terminologies such as pseudocyst,
      necroma, pancreatic abscess, and infected necrosis were previously used in the
      literature, resulting in confusion. The current and past terminologies must be
      reconciled to meaningfully interpret past data. Recently, endoscopic necrosectomy
      was introduced as a treatment option and is now preferred over surgical
      necrosectomy when the expertise is available. However, high-quality evidence is
      still lacking, and there is no standard management strategy for WON. The
      consensus meeting aimed to clarify the diagnostic criteria for WON and the role
      of endoscopic interventions in its management. In the Consensus Conference, 27
      experts from eight Asian countries took an active role and examined key clinical
      aspects of WON diagnosis and endoscopic management. Statements were crafted based
      on literature review and expert opinion, employing the modified Delphi method.
      All statements were substantiated by the level of evidence and the strength of
      the recommendation. We created 27 consensus statements for WON diagnosis and
      management, including details of endoscopic procedures. When there was not enough
      solid evidence to support the statements, this was clearly acknowledged to
      facilitate future research. Proposed management strategies were formulated and
      are illustrated using flow charts. These recommendations, which are based on the
      best current scientific evidence and expert opinion, will be useful for guiding
      endoscopic management of WON. Part 1 of this statement focused on the
      epidemiology, diagnosis, and timing of intervention. 

PMID- 27044025
TI  - Focus on Mass Spectrometry as a Probe of Higher Order Protein Structure, Honoring
      Prof. Brian T. Chait, Recipient of the 2015 ASMS Award for a Distinguished
      Contribution in Mass Spectrometry : Editorial: A Turning Point for Biological
      Mass Spectrometry.

PMID- 27044024
TI  - Ionization Efficiency of Doubly Charged Ions Formed from Polyprotic Acids in
      Electrospray Negative Mode.
AB  - The ability of polyprotic acids to give doubly charged ions in negative mode
      electrospray was studied and related to physicochemical properties of the acids
      via linear discriminant analysis (LDA). It was discovered that the compound has
      to be strongly acidic (low pK a1 and pK a2) and to have high hydrophobicity (logP
      ow) to become multiply charged. Ability to give multiply charged ions in ESI/MS
      cannot be directly predicted from the solution phase acidities. Therefore, for
      the first time, a quantitative model to predict the charge state of the analyte
      in ESI/MS is proposed and validated for small anions. Also, a model to predict
      ionization efficiencies of these analytes was developed. Results indicate that
      acidity of the analyte, its octanol-water partition coefficient, and charge
      delocalization are important factors that influence ionization efficiencies as
      well as charge states of the analytes. The pH of the solvent was also found to be
      an important factor influencing the ionization efficiency of doubly charged ions.
      Graphical Abstract ?.

PMID- 27044026
TI  - The anti-inflammatory effects of E-alpha-(p-methoxyphenyl)-2',3,4,4'
      tetramethoxychalcone are mediated via HO-1 induction.
AB  - Inflammation plays a central role in the pathophysiology of many diseases. The
      inducible enzyme heme oxygenase-1 (HO-1) protects cells against inflammation and
      can be induced by electrophilic compounds like the chalcones (1,3-diphenylprop-2
      enones) from the class of alpha,beta-unsaturated carbonyl compounds. We
      hypothesized that the synthetic chalcone E-alpha-(p-methoxyphenyl)-2',3,4,4'
      tetramethoxychalcone (E-alpha-p-OMe-C6H4-TMC) exerts anti-inflammatory effects in
      RAW264.7, Jurkat lymphocytes and HK-2 cells via HO-1 induction. RAW264.7 cells
      were treated with lipopolysaccharide prior to E-alpha-p-OMe-C6H4-TMC treatment.
      Subsequently, HO-1 protein induction and activity were analyzed, as well as
      expression of pro- and anti-inflammatory mediators, transcription factors and
      mitogen-activated protein kinases to evaluate the possible molecular mechanism.
      These results were confirmed in human cell lines (Jurkat T-lymphocytes and HK-2
      epithelial cells). We found that the E-alpha-p-OMe-C6H4-TMC exerts significant
      anti-inflammatory effects in a dose dependent manner, showing no toxic effects in
      LPS-treated RAW264.7 macrophages. E-alpha-p-OMe-C6H4-TMC induced HO-1 and SOD-1
      protein expression and HO-1 enzyme activity, reduced the upregulation of COX-2
      and iNOS, while inducing the translocation of Nrf2. NF-kappaB activity was
      attenuated following E-alpha-p-OMe-C6H4-TMC treatment accompanied by the
      downregulation of proinflammatory cytokines IL-1beta, IL-6 and MCP-1.
      Pretreatment with E-alpha-p-OMe-C6H4-TMC revealed significant changes in
      phosphorylation of ERK and p38, but not JNK. These anti-inflammatory effects of E
      alpha-p-OMe-C6H4-TMC were approved in Jurkat and HK-2 cells, furthermore
      revealing a downregulation of IL-8 and IL-10. In conclusion, it is tempting to
      speculate about E-alpha-p-OMe-C6H4-TMC as a new and non-toxic agent, inducing HO
      1 in cells. This opens up new opportunities regarding the development of
      therapeutic agents using beneficial effects of HO-1 and its products. 

PMID- 27044027
TI  - The anti-inflammatory and pro-resolution effects of aspirin-triggered RvD1 (AT
      RvD1) on peripheral blood mononuclear cells from patients with severe asthma.
AB  - Asthma is an inflammatory disease that is characterized by a predominance of
      eosinophils and/or neutrophils in the airways. In the resolution of inflammation,
      lipid mediators such as resolvin D1 (RvD1) and its epimer aspirin-triggered RvD1
      (AT-RvD1) are produced and demonstrate anti-inflammatory and pro-resolution
      effects. In experimental models such as airway allergic inflammation induced by
      ovalbumin in mice, RvD1 and AT-RvD1 alleviate some of the most important
      phenotypes of asthma. Here, we demonstrated the effects of AT-RvD1 on peripheral
      blood mononuclear cells (PBMCs) from healthy individuals and patients with severe
      asthma stimulated with lipopolysaccharide (LPS) or Dermatophagoides pteronyssinus
      (DM). AT-RvD1 (100nM) reduced the concentration of TNF-alpha in PBMCs from
      healthy individuals and patients with severe asthma stimulated with LPS or DM. In
      addition, AT-RvD1 lowered the production of IL-10 only in PBMCs from patients
      with severe asthma stimulated with LPS. These effects were associated in part
      with decreasing NF-kappaB activation. Moreover, AT-RvD1 significantly increased
      phagocytosis of apoptotic neutrophils by monocytes from patients with severe
      asthma. In conclusion, AT-RvD1 demonstrated both anti-inflammatory and pro
      resolution effects in PBMCs from patients with severe asthma and could become in
      the future an alternative treatment for asthma. 

PMID- 27044028
TI  - ROSY1, a novel regulator of gravitropic response is a stigmasterol binding
      protein.
AB  - The gravitropic bending in plant roots is caused by asymmetric cell elongation.
      This requires an asymmetric increase in cell surface and therefore plasma
      membrane components such as lipids, sterols, and membrane proteins. We have
      identified an early gravity-regulated protein in Arabidopsis thaliana root apices
      that binds stigmasterol and phosphoethanolamines. This root-specific protein
      interacts with the membrane transport protein synaptotagmin-1 and was therefore
      named InteractoR Of SYnaptotagmin1 (ROSY1). While interactions between ML-domain
      proteins with membrane transport proteins and their impact have been reported
      from animal cell systems, this is the first report of such an interaction in a
      plant system. Homozygous mutants of ROSY1 exhibit decreased basipetal auxin
      transport, a faster root gravitropic response, and an increase in salt stress
      tolerance. Our results suggest that ROSY1 plays a role in root gravitropism,
      possibly by facilitating membrane trafficking and asymmetric cell elongation via
      its interaction with synaptotagmin-1. 

PMID- 27044029
TI  - Improving acoustic streaming effects in fluidic systems by matching SU-8 and
      polydimethylsiloxane layers.
AB  - This paper reports the use of acoustic waves for promoting and improving
      streaming in tridimensional polymethylmethacrylate (PMMA) cuvettes of 15mm
      width*14mm height*2.5mm thickness. The acoustic waves are generated by a 28MUm
      thick poly(vinylidene fluoride) - PVDF - piezoelectric transducer in its beta
      phase, actuated at its resonance frequency: 40MHz. The acoustic transmission
      properties of two materials - SU-8 and polydimethylsiloxane (PDMS) - were
      numerically compared. It was concluded that PDMS inhibits, while SU-8 allows, the
      transmission of the acoustic waves to the propagation medium. Therefore, by
      simulating the acoustic transmission properties of different materials, it is
      possible to preview the acoustic behavior in the fluidic system, which allows the
      optimization of the best layout design, saving costs and time. This work also
      presents a comparison between numerical and experimental results of acoustic
      streaming obtained with that beta-PVDF transducer in the movement and in the
      formation of fluid recirculation in tridimensional closed domains. Differences
      between the numerical and experimental results are credited to the high
      sensitivity of acoustic streaming to the experimental conditions and to
      limitations of the numerical method. The reported study contributes for the
      improvement of simulation models that can be extremely useful for predicting the
      acoustic effects of new materials in fluidic devices, as well as for optimizing
      the transducers and matching layers positioning in a fluidic structure.

PMID- 27044030
TI  - Human identification study by means of frontal sinus imaginological aspects.
AB  - The objective of this study was to evaluate the applicability of human
      identification parameters, established by Tatlisumak et al. (2007), by means of
      cone-beam computed tomography and extraoral radiographs of the frontal sinus
      region. From a total of 58 dry skulls, 26 were selected. Posteroanterior, profile
      cephalometric radiographs and cone-beam computed tomography images were acquired,
      adopting a specific method for reproducibility purposes. The images were
      evaluated by two examiners, previously calibrated, in a darkened environment and
      at two distinct sessions, with a minimum of 15 days between them. The
      characteristics of the frontal sinus were analyzed using the Cohen's kappa test,
      for categorical variables, and Lin's concordance correlation coefficient (CCC)
      for continuous variables. Acceptable values of inter method variability for the
      categorical variables were found, while same cannot be told for continuous
      variables. The parameters evaluated for the frontal sinus on extraoral
      radiographs and cone-beam computed tomographs were mostly concordant, with the
      exception of three. Categorical and discrete variables showed an intra- and
      interexaminer concordance ranging from good to perfect, and the quantitative
      continuous variables showed concordance ranging from moderate to excellent. The
      parameters examined are applicable and reproducible using multiplanar
      reconstructions of cone-beam computed tomography and extraoral radiographs of the
      frontal sinus. 

PMID- 27044031
TI  - Fake turquoises investigated by Raman microscopy.
AB  - Turquoise is frequently adulterated by unscrupulous dealers and, not rarely,
      simulants are commercialized as true stones. On the other hand, turquoise is a
      cryptocrystalline mineral and its use in adornments commonly demands some kind of
      treatment to facilitate its manipulation, such as impregnation using oil or fats,
      consolidation with resin and stabilization or reconstitution made with resins. In
      this work, Raman microscopy was employed in the investigation of turquoise
      adornments aiming to differentiate processed turquoise from fakes or simulants.
      Only one out of the five adornment objects analyzed was truly stabilized
      turquoise (powdered turquoise aggregated with a resin). Another one was
      constituted of turquoise, calcium carbonate, phthalocyanine blue and resin; the
      other objects were dyed minerals. 

PMID- 27044032
TI  - Bullet trajectory reconstruction - Methods, accuracy and precision.
AB  - Based on the spatial relation between a primary and secondary bullet defect or on
      the shape and dimensions of the primary bullet defect, a bullet's trajectory
      prior to impact can be estimated for a shooting scene reconstruction. The
      accuracy and precision of the estimated trajectories will vary depending on
      variables such as, the applied method of reconstruction, the (true) angle of
      incidence, the properties of the target material and the properties of the bullet
      upon impact. This study focused on the accuracy and precision of estimated bullet
      trajectories when different variants of the probing method, ellipse method, and
      lead-in method are applied on bullet defects resulting from shots at various
      angles of incidence on drywall, MDF and sheet metal. The results show that in
      most situations the best performance (accuracy and precision) is seen when the
      probing method is applied. Only for the lowest angles of incidence the
      performance was better when either the ellipse or lead-in method was applied. The
      data provided in this paper can be used to select the appropriate method(s) for
      reconstruction and to correct for systematic errors (accuracy) and to provide a
      value of the precision, by means of a confidence interval of the specific
      measurement. 

PMID- 27044033
TI  - Fingermark age determinations: Legal considerations, review of the literature and
      practical propositions.
AB  - The question of the age of fingermarks is often raised in investigations and
      trials when suspects admit that they have left their fingermarks at a crime scene
      but allege that the contact occurred at a different time than the crime and for
      legal reasons. In the first part of this review article, examples from American
      appellate court cases will be used to demonstrate that there is a lack of
      consensus among American courts regarding the admissibility and weight of
      testimony from expert witnesses who provide opinions about the age of
      fingermarks. Of course, these issues are not only encountered in America but have
      also been reported elsewhere, for example in Europe. The disparity in the way
      fingermark dating cases were managed in these examples is probably due to the
      fact that no methodology has been validated and accepted by the forensic science
      community so far. The second part of this review article summarizes the studies
      reported on fingermark dating in the literature and highlights the fact that most
      proposed methodologies still suffer from limitations preventing their use in
      practice. Nevertheless, several approaches based on the evolution of aging
      parameters detected in fingermark residue over time appear to show promise for
      the fingermark dating field. Based on these approaches, the definition of a
      formal methodological framework for fingermark dating cases is proposed in order
      to produce relevant temporal information. This framework identifies which type of
      information could and should be obtained about fingermark aging and what
      developments are still required to scientifically address dating issues. 

PMID- 27044034
TI  - Treatment for Refractory Myasthenia Gravis-New Lymphs for Old.

PMID- 27044035
TI  - The First Comprehensive Phylogeny of Coptis (Ranunculaceae) and Its Implications
      for Character Evolution and Classification.
AB  - Coptis (Ranunculaceae) contains 15 species and is one of the pharmaceutically
      most important plant genera in eastern Asia. Understanding of the evolution of
      morphological characters and phylogenetic relationships within the genus is very
      limited. Here, we present the first comprehensive phylogenetic analysis of the
      genus based on two plastid and one nuclear markers. The phylogeny was
      reconstructed using Bayesian inference, as well as maximum parsimony and maximum
      likelihood methods. The Swofford-Olsen-Waddell-Hillis and Bayesian tests were
      used to assess the strength of the conflicts between traditional taxonomic units
      and those suggested by the phylogenetic inferences. Evolution of morphological
      characters was inferred using Bayesian method to identify synapomorphies for the
      infrageneric lineages. Our data recognize two strongly supported clades within
      Coptis. The first clade contains subgenus Coptis and section Japonocoptis of
      subgenus Metacoptis, supported by morphological characters, such as traits of the
      central leaflet base, petal color, and petal shape. The second clade consists of
      section Japonocoptis of subgenus Metacoptis. Coptis morii is not united with C.
      quinquefolia, in contrast with the view that C. morii is a synonym of C.
      quinquefolia. Two varieties of C. chinensis do not cluster together. Coptis
      groenlandica and C. lutescens are reduced to C. trifolia and C. japonica,
      respectively. Central leaflet base, sepal shape, and petal blade carry a strong
      phylogenetic signal in Coptis, while leaf type, sepal and petal color, and petal
      shape exhibit relatively higher levels of evolutionary flexibility. 

PMID- 27044036
TI  - PSIONplus: Accurate Sequence-Based Predictor of Ion Channels and Their Types.
AB  - Ion channels are a class of membrane proteins that attracts a significant amount
      of basic research, also being potential drug targets. High-throughput
      identification of these channels is hampered by the low levels of availability of
      their structures and an observation that use of sequence similarity offers
      limited predictive quality. Consequently, several machine learning predictors of
      ion channels from protein sequences that do not rely on high sequence similarity
      were developed. However, only one of these methods offers a wide scope by
      predicting ion channels, their types and four major subtypes of the voltage-gated
      channels. Moreover, this and other existing predictors utilize relatively simple
      predictive models that limit their accuracy. We propose a novel and accurate
      predictor of ion channels, their types and the four subtypes of the voltage-gated
      channels called PSIONplus. Our method combines a support vector machine model and
      a sequence similarity search with BLAST. The originality of PSIONplus stems from
      the use of a more sophisticated machine learning model that for the first time in
      this area utilizes evolutionary profiles and predicted secondary structure,
      solvent accessibility and intrinsic disorder. We empirically demonstrate that the
      evolutionary profiles provide the strongest predictive input among new and
      previously used input types. We also show that all new types of inputs contribute
      to the prediction. Results on an independent test dataset reveal that PSIONplus
      obtains relatively good predictive performance and outperforms existing methods.
      It secures accuracies of 85.4% and 68.3% for the prediction of ion channels and
      their types, respectively, and the average accuracy of 96.4% for the
      discrimination of the four ion channel subtypes. Standalone version of PSIONplus
      is freely available from https://sourceforge.net/projects/psion/. 

PMID- 27044037
TI  - Risk of intracerebral hemorrhage in HIV/AIDS: a systematic review and meta
      analysis.
AB  - Evidence for the association and the increased risk of stroke with human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is growing.
      Recent studies have reported on HIV infection as a potent risk factor for
      intracerebral hemorrhage (ICH). We used the pooled results from case-control
      studies to conduct a systematic review and a meta-analysis in order to evaluate
      the risk of ICH with HIV/AIDS. Our systematic review and meta-analysis was based
      on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      algorithm of all available case-control studies that reported on the risk of ICH
      in patients with HIV/AIDS. Five eligible studies were identified, totaling
      5,310,426 person-years studied over various periods that ranged from 1985 to
      2010. There were a total of 724 cases of ICH, 138 with HIV/AIDS. HIV-infected ICH
      patients were in average younger. Pooled crude incidence rate ratio (IRR) for ICH
      in HIV/AIDS patients was 3.40 (95 % confidence intervals [CI] 1.44-8.04; p =
      0.005, random-effects model). Clinical AIDS was associated with a higher IRR of
      ICH (11.99, 95 % CI 2.84-50.53; p = 0.0007) than HIV+ status without AIDS (1.73,
      95 % CI 1.39-2.16; p < 0.0001). Patients with CD4+ lymphocyte count <200
      cells/mm3 were similarly at a higher risk. Antiretroviral therapy did not seem to
      increase the risk of ICH. The available evidence suggests that HIV/AIDS is an
      important risk factor for ICH, particularly in younger HIV-infected patients and
      those with advanced disease.

PMID- 27044038
TI  - Analysis of a Spontaneous Non-Motile and Avirulent Mutant Shows That FliM Is
      Required for Full Endoflagella Assembly in Leptospira interrogans.
AB  - Pathogenic Leptospira strains are responsible for leptospirosis, a worldwide
      emerging zoonotic disease. These spirochetes are unique amongst bacteria because
      of their corkscrew-like cell morphology and their periplasmic flagella. Motility
      is reported as an important virulence determinant, probably favoring entry and
      dissemination of pathogenic Leptospira in the host. However, proteins
      constituting the periplasmic flagella and their role in cell shape, motility and
      virulence remain poorly described. In this study, we characterized a spontaneous
      L. interrogans mutant strain lacking motility, correlated with the loss of the
      characteristic hook-shaped ends, and virulence in the animal model. Whole genome
      sequencing allowed the identification of one nucleotide deletion in the fliM gene
      resulting in a premature stop codon, thereby preventing the production of
      flagellar motor switch protein FliM. Genetic complementation restored cell
      morphology, motility and virulence comparable to those of wild type cells.
      Analyses of purified periplasmic flagella revealed a defect in flagella assembly,
      resulting in shortened flagella compared to the wild type strain. This also
      correlated with a lower amount of major filament proteins FlaA and FlaB.
      Altogether, these findings demonstrate that FliM is required for full and correct
      assembly of the flagella which is essential for motility and virulence. 

PMID- 27044039
TI  - Developing Subdomain Allocation Algorithms Based on Spatial and Communicational
      Constraints to Accelerate Dust Storm Simulation.
AB  - Dust storm has serious disastrous impacts on environment, human health, and
      assets. The developments and applications of dust storm models have contributed
      significantly to better understand and predict the distribution, intensity and
      structure of dust storms. However, dust storm simulation is a data and computing
      intensive process. To improve the computing performance, high performance
      computing has been widely adopted by dividing the entire study area into multiple
      subdomains and allocating each subdomain on different computing nodes in a
      parallel fashion. Inappropriate allocation may introduce imbalanced task loads
      and unnecessary communications among computing nodes. Therefore, allocation is a
      key factor that may impact the efficiency of parallel process. An allocation
      algorithm is expected to consider the computing cost and communication cost for
      each computing node to minimize total execution time and reduce overall
      communication cost for the entire simulation. This research introduces three
      algorithms to optimize the allocation by considering the spatial and
      communicational constraints: 1) an Integer Linear Programming (ILP) based
      algorithm from combinational optimization perspective; 2) a K-Means and Kernighan
      Lin combined heuristic algorithm (K&K) integrating geometric and coordinate-free
      methods by merging local and global partitioning; 3) an automatic seeded region
      growing based geometric and local partitioning algorithm (ASRG). The performance
      and effectiveness of the three algorithms are compared based on different
      factors. Further, we adopt the K&K algorithm as the demonstrated algorithm for
      the experiment of dust model simulation with the non-hydrostatic mesoscale model
      (NMM-dust) and compared the performance with the MPI default sequential
      allocation. The results demonstrate that K&K method significantly improves the
      simulation performance with better subdomain allocation. This method can also be
      adopted for other relevant atmospheric and numerical modeling. 

PMID- 27044040
TI  - Toward Understanding the Genetic Basis of Yak Ovary Reproduction: A
      Characterization and Comparative Analyses of Estrus Ovary Transcriptiome in Yak
      and Cattle.
AB  - BACKGROUND: Yaks (Bos grunniens) are endemic species that can adapt well to thin
      air, cold temperatures, and high altitude. These species can survive in harsh
      plateau environments and are major source of animal production for local
      residents, being an important breed in the Qinghai-Tibet Plateau. However,
      compared with ordinary cattle that live in the plains, yaks generally have lower
      fertility. Investigating the basic physiological molecular features of yak ovary
      and identifying the biological events underlying the differences between the
      ovaries of yak and plain cattle is necessary to understand the specificity of yak
      reproduction. Therefore, RNA-seq technology was applied to analyze transcriptome
      data comparatively between the yak and plain cattle estrous ovaries. RESULTS:
      After deep sequencing, 3,653,032 clean reads with a total of 4,828,772,880 base
      pairs were obtained from yak ovary library. Alignment analysis showed that 16992
      yak genes mapped to the yak genome, among which, 12,731 and 14,631 genes were
      assigned to Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathways. Furthermore, comparison of yak and cattle ovary
      transcriptome data revealed that 1307 genes were significantly and differentially
      expressed between the two libraries, wherein 661 genes were upregulated and 646
      genes were downregulated in yak ovary. Functional analysis showed that the
      differentially expressed genes were involved in various Gene Ontology (GO)
      categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. GO
      annotations indicated that the genes related to "cell adhesion," "hormonal"
      biological processes, and "calcium ion binding," "cation transmembrane transport"
      molecular events were significantly active. KEGG pathway analysis showed that the
      "complement and coagulation cascade" pathway was the most enriched in yak ovary
      transcriptome data, followed by the "cytochrome P450" related and "ECM-receptor
      interaction" pathways. Moreover, several novel pathways, such as "circadian
      rhythm," were significantly enriched despite having no evident associations with
      the reproductive function. CONCLUSION: Our findings provide a molecular resource
      for further investigation of the general molecular mechanism of yak ovary and
      offer new insights to understand comprehensively the specificity of yak
      reproduction.

PMID- 27044041
TI  - Novel Bioreactor Platform for Scalable Cardiomyogenic Differentiation from
      Pluripotent Stem Cell-Derived Embryoid Bodies.
AB  - Generation of cardiomyocytes from pluripotent stem cells (PSCs) is a common and
      valuable approach to produce large amount of cells for various applications,
      including assays and models for drug development, cell-based therapies, and
      tissue engineering. All these applications would benefit from a reliable
      bioreactor-based methodology to consistently generate homogenous PSC-derived
      embryoid bodies (EBs) at a large scale, which can further undergo cardiomyogenic
      differentiation. The goal of this chapter is to describe a scalable method to
      consistently generate large amount of homogeneous and synchronized EBs from PSCs.
      This method utilizes a slow-turning lateral vessel bioreactor to direct the EB
      formation and their subsequent cardiomyogenic lineage differentiation.

PMID- 27044042
TI  - Isolation and Propagation of Glioma Stem Cells from Acutely Resected Tumors.
AB  - Gliomas are characterized by striking intratumoral cellular heterogeneity. A
      consistent method to isolate undifferentiated GSC fraction from clinical
      specimens provides an opportunity to establish in vitro models that more closely
      mirror the in vivo state compared to traditional serum containing culture
      methods. Here we describe techniques involved with isolation, identification, and
      expansion of human malignant glioma-derived stem cells using a serum-free growth
      condition.

PMID- 27044043
TI  - Automated Cell-Based Quantitation of 8-OHdG Damage.
AB  - Detection of 8-OHdG-base damage has been a big challenge for decades, though
      different analytical methods are developed. The recent approaches that are used
      for quantitating either the total amount of base damage or the amount of base
      damage per cell from different sources of samples are not automated. We have
      developed a method for automated damage detection from a single cell and applied
      it to 8-OHdG quantitation.

PMID- 27044044
TI  - Clonal Analysis of Cells with Cellular Barcoding: When Numbers and Sizes Matter.
AB  - Cellular barcoding is a recently rediscovered tool to trace the clonal output of
      individual cells with genetically distinct and heritable DNA sequences. Each year
      a few dozens of papers are published using the cellular barcoding technique.
      Those publications largely focus on mutually related issues, namely: counting
      cells capable of clonal proliferation and expansion, monitoring clonal dynamics
      in time, tracing the origin of differentiated cells, characterizing the
      differentiation potential of stem cells and similar topics. Apart from their
      biological content, claims and conclusions, these studies show remarkable
      diversity in technical aspects of the barcoding method and sometimes in major
      conclusions. Although a diversity of approaches is quite usual in data analysis,
      deviant handling of barcode data might directly affect experimental results and
      their biological interpretation. Here, we will describe typical challenges and
      caveats in cellular barcoding publications available so far.

PMID- 27044045
TI  - Heterogeneity of Stem Cells: A Brief Overview.
AB  - Stem cells possess the extraordinary capacity of self-renewal and differentiation
      to various cell types, thus to form original tissues and organs. Stem cell
      heterogeneity including genetic and nongenetic mechanisms refers to biological
      differences amongst normal and stem cells originated within the same tissue. Cell
      differentiation hierarchy and stochasticity in gene expression and signaling
      pathways may result in phenotypic differences of stem cells. The maintenance of
      stemness and activation of differentiation potential are fundamentally
      orchestrated by microenvironmental stem cell niche-related cellular and humoral
      signals.

PMID- 27044046
TI  - Agent-Based Modeling of Cancer Stem Cell Driven Solid Tumor Growth.
AB  - Computational modeling of tumor growth has become an invaluable tool to simulate
      complex cell-cell interactions and emerging population-level dynamics. Agent
      based models are commonly used to describe the behavior and interaction of
      individual cells in different environments. Behavioral rules can be informed and
      calibrated by in vitro assays, and emerging population-level dynamics may be
      validated with both in vitro and in vivo experiments. Here, we describe the
      design and implementation of a lattice-based agent-based model of cancer stem
      cell driven tumor growth.

PMID- 27044047
TI  - Enzyme-Free Dissociation of Neurospheres by a Microfluidic Chip-Based Method.
AB  - Neurosphere assay is a common and robust method for identification of neural
      stem/progenitor cells, but obtaining large numbers of live single cells from
      dissociated neurospheres is difficult using nonenzymatic methods. Here, we
      present an enzyme-free method for high-efficiency neurosphere dissociation into
      single cells using microfluidic device technology. This method allows single cell
      dissociation of DC115 and KT98 cells with high cell viabilities (80-85 %), single
      cell yield (91-95 %), and recovery (75-93 %).

PMID- 27044048
TI  - Establishment and Characterization of Naive Pluripotency in Human Embryonic Stem
      Cells.
AB  - Mouse embryonic stem cells are known to represent the naive state of
      pluripotency, while human embryonic stem cells typically represented the primed
      state of pluripotency, characterized by a higher drift toward differentiation and
      some other disadvantages. Here we describe an efficient method for rapid,
      transgene free induction of the naive pluripotent state in human by applying a
      novel combination of small molecules and growth factors in the culture medium
      (2i, LIF, basic fibroblast growth factor, ascorbic acid, and forskolin).
      Conversion of primed human embryonic stem cells towards the naive pluripotent
      state should be confirmed by a detailed characterization of the cells, as
      described in this chapter.

PMID- 27044049
TI  - Salt Intake and Health Risk in Climate Change Vulnerable Coastal Bangladesh: What
      Role Do Beliefs and Practices Play?
AB  - BACKGROUND: High salt consumption is an important risk factor of elevated blood
      pressure. In Bangladesh about 20 million people are at high risk of hypertension
      due to climate change induced saline intrusion in water. The objective of this
      study is to assess beliefs, perceptions, and practices associated with salt
      consumption in coastal Bangladesh. METHODS: The study was conducted in Chakaria,
      Bangladesh between April-June 2011. It was a cross sectional mixed method study.
      For the qualitative study 6 focus group discussions, 8 key informant interviews,
      60 free listing exercises, 20 ranking exercises and 10 observations were
      conducted. 400 adults were randomly selected for quantitative survey. For
      analysis we used SPSS for quantitative data, and Anthropac and Nvivo for
      qualitative data. RESULTS: Salt was described as an essential component of food
      with strong cultural and religious roots. People described both health benefits
      and risks related to salt intake. The overall risk perception regarding excessive
      salt consumption was low and respondents believed that the cooking process can
      render the salt harmless. Respondents were aware that salt is added in many foods
      even if they do not taste salty but did not recognize that salt can occur
      naturally in both foods and water. CONCLUSIONS: In the study community people had
      low awareness of the risks associated with excess salt consumption and salt
      reduction strategies were not high in their agenda. The easy access to and low
      cost of salt as well as unrecognised presence of salt in drinking water has
      created an environment conducive to excess salt consumption. It is important to
      design general messages related to salt reduction and test tailored strategies
      especially for those at high risk of hypertension.

PMID- 27044050
TI  - Complementary Feeding Practices of Mothers and Their Perceived Impacts on Young
      Children: Findings from KEEA District of Ghana.
AB  - Objective Appropriate and timely complementary feeding practices are fundamental
      to a child's growth, health, and development during the first 2 years of life.
      This study aimed to understand (1) Ghanaian mother's complementary feeding
      practices, and (2) their perceived and observed impacts of complementary feeding
      on their children. Methods Ghanaian mothers with children 4-24 months of age were
      recruited from four communities in the Komenda Edina Eguafo Abrem district in the
      Central Region of Ghana (n = 99). A qualitative methodological approach with
      focus group interview discussions was used. Eleven focus group interviews were
      conducted, and were audio recorded and transcribed. The audio transcriptions were
      coded and analyzed into pertinent themes, meta-themes, and theoretical concepts.
      Results Over 80 % (85) of mothers reported poor knowledge about the effects of
      complementary feeding on their children and 45 % (45) of the children were
      undernourished, indicating inappropriate complementary feeding practices. Some
      mothers held misconceptions about the effect of food on children's health. Four
      overarching themes were identified: (1) mothers' background knowledge about food,
      child health and growth outcomes, (2) mothers' motivation in feeding their
      children, (3) barriers to feeding, (4) foods mothers offered their children.
      Conclusion for Practice Nutrition education on complementary feeding is needed
      for Ghanaian mothers. Health facilities and community outreach programs could be
      a venue to provide education to mothers regarding infant and young child feeding
      practices in Ghana.

PMID- 27044051
TI  - Cellular architecture and transmitter phenotypes of neurons of the mouse median
      raphe region.
AB  - The median raphe region (MRR, which consist of MR and paramedian raphe regions)
      plays a crucial role in regulating cortical as well as subcortical network
      activity and behavior, while its malfunctioning may lead to disorders, such as
      schizophrenia, major depression, or anxiety. Mouse MRR neurons are classically
      identified on the basis of their serotonin (5-HT), vesicular glutamate
      transporter type 3 (VGLUT3), and gamma-aminobutyric acid (GABA) contents;
      however, the exact cellular composition of MRR regarding transmitter phenotypes
      is still unknown. Using an unbiased stereological method, we found that in the
      MR, 8.5 % of the neurons were 5-HT, 26 % were VGLUT3, and 12.8 % were 5-HT and
      VGLUT3 positive; whereas 37.2 % of the neurons were GABAergic, and 14.4 % were
      triple negative. In the whole MRR, 2.1 % of the neurons were 5-HT, 7 % were
      VGLUT3, and 3.6 % were 5-HT and VGLUT3 positive; whereas 61 % of the neurons were
      GABAergic. Surprisingly, 25.4 % of the neurons were triple negative and were only
      positive for the neuronal marker NeuN. PET-1/ePET-Cre transgenic mouse lines are
      widely used to specifically manipulate only 5-HT containing neurons.
      Interestingly, however, using the ePET-Cre transgenic mice, we found that far
      more VGLUT3 positive cells expressed ePET than 5-HT positive cells, and about 38
      % of the ePET cells contained only VGLUT3, while more than 30 % of 5-HT cells
      were ePET negative. These data should facilitate the reinterpretation of PET
      1/ePET related data in the literature and the identification of the functional
      role of a putatively new type of triple-negative neuron in the MRR.

PMID- 27044052
TI  - The Influence of Environmental Consequences and Internalizing Symptoms on
      Children's Tic Severity.
AB  - Although there is evidence that environmental consequences for displaying tics
      and internalizing symptoms are related to tic severity in children with TS, less
      is known about the inter-relationships of these variables or how these factors
      jointly contribute to tic severity. This study included 45 children with Tourette
      syndrome. Caregivers reported on children's environmental consequences for
      displaying tics, internalizing symptoms, and tic severity. Results indicated that
      children with higher levels of internalizing symptoms experienced significantly
      more environmental consequences for displaying tics. Children with higher levels
      of separation anxiety symptoms demonstrated significantly greater tic severity.
      Environmental consequences for displaying tics accounted for significantly more
      variance in predicting tic severity than anxiety symptoms. This preliminary
      evidence suggests that environmental consequences for displaying tics, such as
      receiving accommodations or attention from others, have a greater influence on
      children's tic severity than emotional factors.

PMID- 27044053
TI  - The Two-Sided Face of Antidepressants: The Impact of Their Use on Real-Life
      Affective Change during Mindfulness-Based Cognitive Therapy.

PMID- 27044054
TI  - Enantioselective organocatalytic Michael addition of isorhodanines to alpha,beta
      unsaturated aldehydes.
AB  - The Michael reaction of substituted isorhodanines with alpha,beta-unsaturated
      aldehydes in the presence of a catalytic amount of a chiral secondary amine is
      presented. This transformation proceeds in good to high yields furnishing the
      corresponding 4,5-disubstituted isorhodanine adducts in good to excellent
      enantioselectivities. 

PMID- 27044055
TI  - Fourth stable radical species in X-irradiated solid-state sucrose.
AB  - High-energy radiation produces radicals in crystalline sucrose. As such, sucrose
      is considered as a relevant model system for studying radiation damage to the
      sugar units of DNA. Many of these radicals are stable, detectable at room
      temperature with electron paramagnetic resonance (EPR) and their concentration is
      proportional to the absorbed dose in a considerable range. This makes sucrose
      also an interesting system for dosimetry. Dose assessment protocols rely on
      measurements of the total intensity of the EPR powder spectrum, so it is likely
      that they could be further improved if the composite nature of the spectrum was
      understood completely. Recently, it was shown that the three known stable
      radicals can only account for the central part of the spectrum and that features
      in the wings remain unidentified. In this work, we show, based on the analysis of
      the powder EPR patterns recorded at three microwave frequencies, that the
      contribution of one more species is sufficient to explain the entire spectrum.
      The determination of the spin Hamiltonian parameters is corroborated by a Q-band
      (34 GHz) single crystal electron-nuclear double resonance (ENDOR) analysis. The
      chemical structure of the fourth species is explored by analysis of the
      determined g and four (1)H hyperfine (HF) tensors, and verified using density
      functional theory (DFT) calculations. The ENDOR spectrum of the largest HF
      interaction of the fourth species was exploited to isolate the radical's
      absorption-like EPR spectrum from a multicomponent powder pattern. 

PMID- 27044056
TI  - meso-Mono-[4-(1,4,7-triazacyclononanyl)]-tri(phenyl)]porphyrin and the respective
      zinc(ii)-complex: complete characterization and biomolecules binding abilities.
AB  - We aimed to synthesize a new series of triazacyclononanyl-porphyrins (4 and 5)
      with the potential ability to bind DNA. For this, the free-base porphyrin 4 and
      the corresponding Zn(ii)-complex 5 were synthesized by the Schiff base formation
      reaction. The binding ability of the porphyrin derivatives 4 and 5 with DNA from
      calf-thymus was studied by UV-vis and emission spectroscopy. Detailed analysis of
      the results suggests that the interaction of these systems most probably occurs
      through pi-stacking and secondary hydrogen interaction surface binding with ct
      DNA. Moreover, we also demonstrate the substantial ability of porphyrins 4 and 5
      to generate (1)O2 and to photocleave plasmid DNA after irradiation. 

PMID- 27044057
TI  - Coping With Prediagnosis Symptoms of Colorectal Cancer: A Study of 244
      Individuals With Recent Diagnosis.
AB  - BACKGROUND: Colorectal cancer (CRC) symptoms are often vague and vary in
      severity, intensity, type, and timing. Receipt of medical care is dependent on
      symptom recognition and assessment, which may impede timely diagnosis. OBJECTIVE:
      The aim of this study was to describe and categorize how CRC patients coped with
      symptoms prior to seeking medical care, examine sociodemographic differences in
      these coping strategies, and determine the strategies associated with time to
      seek medical care and overall time to diagnosis. METHODS: Two hundred forty-four
      white and African American patients in Virginia and Ohio who received a diagnosis
      of CRC and who experienced symptoms prior to diagnosis were administered a
      semistructured interview and the Brief COPE questionnaire. RESULTS: Eighty-three
      percent used more than 1 coping strategy. Common symptom-specific coping
      strategies were to "wait-and-see," self-treat, and rationalize symptoms. Males
      were more likely to wait and see (P < .001); African Americans and Medicaid
      recipients were more likely to self-treat via lifestyle changes (P's < .01).
      Younger individuals (<50 years old) had higher Brief COPE reframing, planning,
      and humor scores; those with lower education and income had higher denial scores
      (P's < .01). Using more symptom-specific coping strategies and engaging in
      avoidance/denial were associated with longer time to seek medical care and
      overall time to diagnosis (P's < .01). CONCLUSIONS: Individuals experiencing CRC
      symptoms use multiple, diverse coping strategies that are influenced by
      sociodemographic characteristics. Denial is particularly relevant for delay in
      seeking care and timely diagnosis. IMPLICATIONS FOR PRACTICE: Public health
      campaigns could focus on secondary prevention of CRC by targeting at-risk groups
      such as males, African Americans, or Medicaid recipients, who choose waiting or
      self-treatment in response to initial symptoms.

PMID- 27044058
TI  - Communication During Palliative Care and End of Life: Perceptions of Experienced
      Pediatric Oncology Nurses.
AB  - BACKGROUND: Communication between patients, families, and healthcare providers is
      a central component of end-of-life care. Nurse communication during palliative
      care (PC) and end of life (EOL) is a phenomenon with limited research. It is
      unclear how the level of nursing experience influences the perspectives of nurses
      communicating during EOL. OBJECTIVE: The aim of this study is to describe the
      commonalities of experienced nurses' perceptions of communicating during PC and
      EOL and perceptions of barriers and facilitators to effective communication.
      METHODS: This study was part of a larger multisite study that used a qualitative,
      empirical phenomenology design and represents focus group data gathered from
      pediatric oncology nurses with more than 5 years of experience or who were
      advanced practice nurses not involved in the direct evaluation of other nurses.
      RESULTS: Five core themes with corresponding themes and subthemes were
      identified. The core themes included (a) Evolution of PC/EOL, (b) Skill of
      Knowing, (c) Expanded Essence of Caring, (d) Experienced Nurse as Committed
      Advocate, and (e) Valuing Individual Response to Grief. CONCLUSIONS: Findings
      reflect how the concept of experience transcended the 5 core themes and captured
      how experience provided nurses the know-how to fulfill the roles of
      communication, caring, and advocacy for children and families. IMPLICATIONS FOR
      PRACTICE: Enhancing nurse communication skills during EOL requires opportunities
      to gain experience coupled with clinical strategies, such as standardized
      curricula, simulation, competency-based orientation programs, mentorship, and
      peer support.

PMID- 27044059
TI  - Penis Cancer: The Lived Experience.
AB  - BACKGROUND: This qualitative study examined the experiences of men with penis
      cancer. Cancer of the penis is a rare and debilitating disease, affecting 1 in
      100 000 men in Western countries. Although much has been written about the
      medical treatment of the disease, little has been published about the experiences
      of men who have penis cancer. OBJECTIVE: The aim of this study is to gain an
      understanding of the lived experiences of men with cancer of the penis. METHODS:
      Using face-to-face audio-taped interviews with a semi-structured guide, the
      researcher recruited a purposive sample of 13 men who had been treated for penile
      cancer. Heidegger's hermeneutic phenomenology served as the philosophical
      underpinning and Colazzi's method was used to analyze the data. RESULTS: Six main
      themes emerged from the data: Misdiagnosis, Secrecy, "Cancer is cancer," Sexual
      Issues, Support, and Awareness and Prevention. CONCLUSIONS: Men diagnosed and
      treated for penis cancer reported numerous issues related to misdiagnosis,
      delayed treatment, and reluctance to share experience with family, friends, and
      coworkers. IMPLICATIONS FOR PRACTICE: Gaining more knowledge of the experiences
      of men with penile cancer will provide additional insights for healthcare
      providers to create holistic practice guidelines for the care of men and their
      loved ones who are affected. It is recommended to change the terminology to penis
      cancer, instead of penile cancer, to promote public awareness, education,
      prevention, and early treatment.

PMID- 27044060
TI  - Patients' Vulnerability in Follow-up After Colorectal Cancer: A Qualitative
      Action Research Study.
AB  - BACKGROUND: In the transition between being a hospitalized patient with cancer
      and resuming "normal" life, many patients experience physical, mental, and social
      challenges. Scientifically, as well as politically, it is therefore recommended
      to undertake research with a focus on rethinking and reorganizing follow-up after
      cancer treatment. OBJECTIVE: The aim of this study was to identify the
      perspectives of fast-track colorectal cancer surgery patients on challenges
      experienced in the transition from being a hospitalized patient with cancer to
      being a cancer survivor. METHODS: The current article represents phase 1 in an
      ongoing action research project. Data were analyzed by using the "interpretive
      description" method. RESULTS: Twelve patients (6 male and 6 female patients; mean
      age, 72.4 years) participated in the study. The analyses show that the patients
      physically experienced readiness to leave hospital after a few days; however,
      shortly after returning home, most of them became mentally overwhelmed by the
      feeling of vulnerability that was closely related to the feeling of being handed
      over the responsibility for a newly cancer-operated body and a fragile life
      situation. Four issues that challenged the patients emerged from the analysis:
      restore an everyday life, participate in a follow-up program, get relevant
      information, and manage contact with relevant health professionals. CONCLUSIONS:
      The study indicates that the transition to restoring a normal life after cancer
      surgery had been an experience characterized by more vulnerability than expected
      by the patients in the study. IMPLICATIONS FOR PRACTICE: The findings provide 4
      well-defined themes, each of which constitutes a point of departure related to
      focused patient-centered interventions related to follow-up after cancer surgery.

PMID- 27044061
TI  - Improving the Transition to Palliative Care for Patients With Acute Leukemia: A
      Coordinated Care Approach.
AB  - BACKGROUND: Currently, there is little guidance available for documenting and
      executing the change in management goals in the context of incurable hematologic
      disease. OBJECTIVE: The aim of this study was to improve the transition to
      palliative care for patients with acute myeloid leukemia (AML) through the
      development and implementation of a coordinated care plan program. METHODS:
      Twenty-three patients with AML who were no longer being treated with curative
      intent from March 2011 through September 2012 had hematology supportive care
      plans developed. Patients (n = 7) completed post-care plan implementation
      questionnaires to determine their level of understanding in relation to the
      change in treatment intent. Staff completed pre- (n = 26) and post- (n = 19) care
      plan implementation questionnaires to determine the communication, challenges,
      and accessibility of changed management goals. RESULTS: Seventy-seven percent of
      patients understood palliative care to be the primary team managing their
      symptoms, with 75% of patients viewing symptom control as the main goal of
      treatment. Staff findings demonstrated a significant improvement in the
      communication of treatment goals (53% preimplementation vs 86%
      postimplementation). Early timing of referrals remains a significant issue.
      CONCLUSIONS: Implementing the individualized care plan program was associated
      with better communication and accessibility of documented palliative treatment
      goals for patients with AML. IMPLICATIONS FOR PRACTICE: This study establishes a
      model of care that addresses symptom and disease burden in end-stage AML and
      provides valuable insight into the patient and family understanding of treatment
      intent during this terminal phase.

PMID- 27044062
TI  - The Relationship Between Inflammatory Biomarkers and Symptom Distress in Lung
      Cancer Patients Undergoing Chemotherapy.
AB  - BACKGROUND: Symptom distress often occurs in lung cancer patients undergoing
      chemotherapy. However, a biomarker has not been identified to reflect the
      severity of their symptom distress. OBJECTIVE: The aim of this study was to
      investigate the relationship between symptom distress and serum inflammatory
      biomarkers in lung cancer patients undergoing chemotherapy. METHODS: A
      longitudinal, repeated-measures design was used to assess subjective symptoms
      (fatigue, sleep disturbance, pain, depression, and confusion), serum biomarkers
      (tartrate-resistant acid phosphatase 5a [TRACP5a], interleukin 6 [IL-6], IL-8,
      and C-reactive protein), and white blood cells in 62 lung cancer patients
      recruited from a single medical center at 3 time points: T1 was the baseline, T2
      was the eighth day after the first chemotherapy cycle, and T3 was prior to the
      second cycle. Symptom distress was measured individually by 5 questionnaires
      (General Fatigue Scale, Pittsburgh Sleep Quality Index, Brief Pain Inventory,
      Profile of Mood States-Depressive, and Confusion). RESULTS: The trend of TRACP5a
      was positively correlated to the trend of the patients' symptom distress.
      However, the trends of IL-6 and IL-8 did not correlate. CONCLUSIONS: Serum
      TRACP5a was associated with symptom distress in lung cancer patients. Therefore,
      TRACP5a might be a potential biomarker to assess symptom distress of lung cancer
      patients undergoing chemotherapy. IMPLICATIONS FOR PRACTICE: Oncology nurses may
      be able to apply TRACP5a expression to predict or monitor multiple distress
      symptoms in lung cancer patients undergoing chemotherapy. Furthermore, nurses can
      use these study findings to better understand the patients who need more
      attention to improve their quality of life.

PMID- 27044063
TI  - Trade-off between the Mechanical Strength and Microwave Electrical Properties of
      Functionalized and Irradiated Carbon Nanotube Sheets.
AB  - Carbon nanotube (CNT) sheets represent a novel implementation of CNTs that enable
      the tailoring of electrical and mechanical properties for applications in the
      automotive and aerospace industries. Small molecule functionalization and
      postprocessing techniques, such as irradiation with high-energy particles, are
      methods that can enhance the mechanical properties of CNTs. However, the effect
      that these modifications have on the electrical conduction mechanisms has not
      been extensively explored. By characterizing the mechanical and electrical
      properties of multiwalled carbon nanotube (MWCNT) sheets with different
      functional groups and irradiation doses, we can expand our insights into the
      extent of the trade-off that exists between mechanical strength and electrical
      conductivity for commercially available CNT sheets. Such insights allow for the
      optimization of design pathways for engineering applications that require a
      balance of material property enhancements. 

PMID- 27044064
TI  - Protein permeation through an electrically tunable membrane.
AB  - Protein filtration is important in many fields of science and technology such as
      medicine, biology, chemistry, and engineering. Recently, protein separation and
      filtering with nanoporous membranes has attracted interest due to the possibility
      of fast separation and high throughput volume. This, however, requires
      understanding of the protein's dynamics inside and in the vicinity of the
      nanopore. In this work, we utilize a Brownian dynamics approach to study the
      motion of the model protein insulin in the membrane-electrolyte electrostatic
      potential. We compare the results of the atomic model of the protein with the
      results of a coarse-grained and a single-bead model, and find that the coarse
      grained representation of protein strikes the best balance between the accuracy
      of the results and the computational effort required. Contrary to common belief,
      we find that to adequately describe the protein, a single-bead model cannot be
      utilized without a significant effort to tabulate the simulation parameters.
      Similar to results for nanoparticle dynamics, our findings also indicate that the
      electric field and the electro-osmotic flow due to the applied membrane and
      electrolyte biases affect the capture and translocation of the biomolecule by
      either attracting or repelling it to or from the nanopore. Our computational
      model can also be applied to other types of proteins and separation conditions. 

PMID- 27044065
TI  - Encapsulation layer design and scalability in encapsulated vertical 3D RRAM.
AB  - Here we propose a novel encapsulated vertical 3D RRAM structure with each
      resistive switching cell encapsulated by dielectric layers, contributing to both
      the reliability improvement of individual cells and thermal disturbance reduction
      of adjacent cells due to the effective suppression of unwanted oxygen vacancy
      diffusion. In contrast to the traditional vertical 3D RRAM, encapsulated bar
      electrodes are adopted in the proposed structure substituting the previous plane
      electrodes, thus encapsulated resistive switching cells can be naturally formed
      by simply oxidizing the tip of the metal bar-electrodes. In this work, TaO x 
      based 3D RRAM devices with SiO2 and Si3N4 as encapsulation layers are
      demonstrated, both showing significant advantages over traditional unencapsulated
      vertical 3D RRAM. Furthermore, it was found thermal conductivity and oxygen
      blocking ability are two key parameters of the encapsulation layer design
      influencing the scalability of vertical 3D RRAM. Experimental and simulation data
      show that oxygen blocking ability is more critical for encapsulation layers in
      the relatively large scale, while thermal conductivity becomes dominant as the
      stacking layers scale to the sub-10 nm regime. Finally, based on the notable
      impacts of the encapsulation layer on 3D RRAM scaling, an encapsulation material
      with both excellent oxygen blocking ability and high thermal conductivity such as
      AlN is suggested to be highly desirable to maximize the advantages of the
      proposed encapsulated structure. The findings in this work could pave the way for
      reliable ultrahigh-density storage applications in the big data era. 

PMID- 27044066
TI  - Synthesis and characterization of a BaGdF5:Tb glass ceramic as a nanocomposite
      scintillator for x-ray imaging.
AB  - Transparent glass ceramics with embedded light-emitting nanocrystals show great
      potential as low-cost nanocomposite scintillators in comparison to single crystal
      and transparent ceramic scintillators. In this study, cubic structure BaGdF5:Tb
      nanocrystals embedded in an aluminosilicate glass matrix are reported for
      potential high performance MeV imaging applications. Scintillator samples with
      systematically varied compositions were prepared by a simple conventional melt
      quenching method followed by annealing. Optical, structural and scintillation
      properties were characterized to guide the design and optimization of selected
      material systems, aiming at the development of a system with higher crystal
      volume and larger crystal size for improved luminosity. It is observed that
      enhanced scintillation performance was achieved by tuning the glass matrix
      composition and using GdF3 in the raw materials, which served as a nucleation
      agent. A 26% improvement in light output was observed from a BaGdF5:Tb glass
      ceramic with addition of GdF3. 

PMID- 27044067
TI  - Fluorinated graphene suspension for inkjet printed technologies.
AB  - The possibility to control the size of the flakes of graphene suspension in the
      course of their fluorination in an aqueous hydrofluoric acid solution was
      demonstrated. The effect of the suspension composition, the fluorination time,
      temperature and thermal stress on the fragmentation process was investigated. The
      corrugation of suspension flakes, which occurs at fluorination due to a
      difference in the constants of graphene and fluorographene lattices, leads to the
      appearance of nonuniform mechanical stresses. The fact that the flake size after
      fragmentation is determined by the size of corrugation allows the assumption that
      the driving force of fragmentation is this mechanical stress. This assumption is
      confirmed by the break of the corrugated layers from flakes under thermal stress.
      Moreover, fluorination treatment at elevated temperatures (~70  degrees C)
      significantly accelerates the fragmentation process. Suspensions of fluorinated
      graphene with nanometer size flakes are of interest for the development of 2D ink
      jet printing technologies and production of thermally and chemically stable
      dielectric films for nanoelectronics. The printed fluorinated graphene films on
      silicon and flexible substrates have been demonstrated and the charges in metal
      insulator-semiconductor structures have been estimated as the ultra low values of
      (0.5-2) * 10(10) cm(-2).

PMID- 27044068
TI  - How to explain microemulsions formed by solvent mixtures without conventional
      surfactants.
AB  - Ternary solutions containing one hydrotrope (such as ethanol) and two immiscible
      fluids, both being soluble in the hydrotrope at any proportion, show unexpected
      solubilization power and allow strange but yet unexplained membrane enzyme
      activity. We study the system ethanol-water-octanol as a simple model of such
      kinds of ternary solutions. The stability of "detergentless" micelles or
      microemulsions in such mixtures was proposed in the pioneering works of Barden
      and coworkers [Smith GD, Donelan CE, Barden RE (1977)J Colloid Interface
      Sci60(3):488-496 and Keiser BA, Varie D, Barden RE, Holt SL (1979)J Phys
      Chem83(10):1276-1281] in the 1970s and then, neglected, because no general
      explanation for the observations was available. Recent direct microstructural
      evidence by light, X-ray, and neutron scattering using contrast variation
      reopened the debate. We propose here a general principle for solubilization
      without conventional surfactants: the balance between hydration force and
      entropy. This balance explains the stability of microemulsions in homogeneous
      ternary mixtures based on cosolvents. 

PMID- 27044069
TI  - Racial bias in pain assessment and treatment recommendations, and false beliefs
      about biological differences between blacks and whites.
AB  - Black Americans are systematically undertreated for pain relative to white
      Americans. We examine whether this racial bias is related to false beliefs about
      biological differences between blacks and whites (e.g., "black people's skin is
      thicker than white people's skin"). Study 1 documented these beliefs among white
      laypersons and revealed that participants who more strongly endorsed false
      beliefs about biological differences reported lower pain ratings for a black (vs.
      white) target. Study 2 extended these findings to the medical context and found
      that half of a sample of white medical students and residents endorsed these
      beliefs. Moreover, participants who endorsed these beliefs rated the black (vs.
      white) patient's pain as lower and made less accurate treatment recommendations.
      Participants who did not endorse these beliefs rated the black (vs. white)
      patient's pain as higher, but showed no bias in treatment recommendations. These
      findings suggest that individuals with at least some medical training hold and
      may use false beliefs about biological differences between blacks and whites to
      inform medical judgments, which may contribute to racial disparities in pain
      assessment and treatment. 

PMID- 27044070
TI  - Photodegradation alleviates the lignin bottleneck for carbon turnover in
      terrestrial ecosystems.
AB  - A mechanistic understanding of the controls on carbon storage and losses is
      essential for our capacity to predict and mitigate human impacts on the global
      carbon cycle. Plant litter decomposition is an important first step for carbon
      and nutrient turnover, and litter inputs and losses are essential in determining
      soil organic matter pools and the carbon balance in terrestrial ecosystems.
      Photodegradation, the photochemical mineralization of organic matter, has been
      recently identified as a mechanism for previously unexplained high rates of
      litter mass loss in arid lands; however, the global significance of this process
      as a control on carbon cycling in terrestrial ecosystems is not known. Here we
      show that, across a wide range of plant species, photodegradation enhanced
      subsequent biotic degradation of leaf litter. Moreover, we demonstrate that the
      mechanism for this enhancement involves increased accessibility to plant litter
      carbohydrates for microbial enzymes. Photodegradation of plant litter, driven by
      UV radiation, and especially visible (blue-green) light, reduced the structural
      and chemical bottleneck imposed by lignin in secondary cell walls. In leaf litter
      from woody species, specific interactions with UV radiation obscured facilitative
      effects of solar radiation on biotic decomposition. The generalized effect of
      sunlight exposure on subsequent microbial activity, mediated by increased
      accessibility to cell wall polysaccharides, suggests that photodegradation is
      quantitatively important in determining rates of mass loss, nutrient release, and
      the carbon balance in a broad range of terrestrial ecosystems. 

PMID- 27044071
TI  - A neural link between affective understanding and interpersonal attraction.
AB  - Being able to comprehend another person's intentions and emotions is essential
      for successful social interaction. However, it is currently unknown whether the
      human brain possesses a neural mechanism that attracts people to others whose
      mental states they can easily understand. Here we show that the degree to which a
      person feels attracted to another person can change while they observe the
      other's affective behavior, and that these changes depend on the observer's
      confidence in having correctly understood the other's affective state. At the
      neural level, changes in interpersonal attraction were predicted by activity in
      the reward system of the observer's brain. Importantly, these effects were
      specific to individual observer-target pairs and could not be explained by a
      target's general attractiveness or expressivity. Furthermore, using multivoxel
      pattern analysis (MVPA), we found that neural activity in the reward system of
      the observer's brain varied as a function of how well the target's affective
      behavior matched the observer's neural representation of the underlying affective
      state: The greater the match, the larger the brain's intrinsic reward signal.
      Taken together, these findings provide evidence that reward-related neural
      activity during social encounters signals how well an individual's "neural
      vocabulary" is suited to infer another person's affective state, and that this
      intrinsic reward might be a source of changes in interpersonal attraction. 

PMID- 27044072
TI  - Axial superresolution via multiangle TIRF microscopy with sequential imaging and
      photobleaching.
AB  - We report superresolution optical sectioning using a multiangle total internal
      reflection fluorescence (TIRF) microscope. TIRF images were constructed from
      several layers within a normal TIRF excitation zone by sequentially imaging and
      photobleaching the fluorescent molecules. The depth of the evanescent wave at
      different layers was altered by tuning the excitation light incident angle. The
      angle was tuned from the highest (the smallest TIRF depth) toward the critical
      angle (the largest TIRF depth) to preferentially photobleach fluorescence from
      the lower layers and allow straightforward observation of deeper structures
      without masking by the brighter signals closer to the coverglass. Reconstruction
      of the TIRF images enabled 3D imaging of biological samples with 20-nm axial
      resolution. Two-color imaging of epidermal growth factor (EGF) ligand and
      clathrin revealed the dynamics of EGF-activated clathrin-mediated endocytosis
      during internalization. Furthermore, Bayesian analysis of images collected during
      the photobleaching step of each plane enabled lateral superresolution (<100 nm)
      within each of the sections. 

PMID- 27044073
TI  - Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of
      eukaryotic chemotaxis.
AB  - Chemotactic eukaryote cells can sense chemical gradients over a wide range of
      concentrations via heterotrimeric G-protein signaling; however, the underlying
      wide-range sensing mechanisms are only partially understood. Here we report that
      a novel regulator of G proteins, G protein-interacting protein 1 (Gip1), is
      essential for extending the chemotactic range ofDictyosteliumcells. Genetic
      disruption of Gip1 caused severe defects in gradient sensing and directed cell
      migration at high but not low concentrations of chemoattractant. Also, Gip1 was
      found to bind and sequester G proteins in cytosolic pools. Receptor activation
      induced G-protein translocation to the plasma membrane from the cytosol in a Gip1
      dependent manner, causing a biased redistribution of G protein on the membrane
      along a chemoattractant gradient. These findings suggest that Gip1 regulates G
      protein shuttling between the cytosol and the membrane to ensure the availability
      and biased redistribution of G protein on the membrane for receptor-mediated
      chemotactic signaling. This mechanism offers an explanation for the wide-range
      sensing seen in eukaryotic chemotaxis. 

PMID- 27044074
TI  - BKCa channel regulates calcium oscillations induced by alpha-2-macroglobulin in
      human myometrial smooth muscle cells.
AB  - The large-conductance, voltage-gated, calcium (Ca(2+))-activated potassium
      channel (BKCa) plays an important role in regulating Ca(2+)signaling and is
      implicated in the maintenance of uterine quiescence during pregnancy. We used
      immunopurification and mass spectrometry to identify proteins that interact with
      BKCain myometrium samples from term pregnant (>=37 wk gestation) women. From this
      screen, we identified alpha-2-macroglobulin (alpha2M). We then used
      immunoprecipitation followed by immunoblot and the proximity ligation assay to
      confirm the interaction between BKCaand both alpha2M and its receptor, low
      density lipoprotein receptor-related protein 1 (LRP1), in cultured primary human
      myometrial smooth muscle cells (hMSMCs). Single-channel electrophysiological
      recordings in the cell-attached configuration demonstrated that activated alpha2M
      (alpha2M*) increased the open probability of BKCain an oscillatory pattern in
      hMSMCs. Furthermore, alpha2M* caused intracellular levels of Ca(2+)to oscillate
      in oxytocin-primed hMSMCs. The initiation of oscillations required an interaction
      between alpha2M* and LRP1. By using Ca(2+)-free medium and inhibitors of various
      Ca(2+)signaling pathways, we demonstrated that the oscillations required entry of
      extracellular Ca(2+)through store-operated Ca(2+)channels. Finally, we found that
      the specific BKCablocker paxilline inhibited the oscillations, whereas the
      channel opener NS11021 increased the rate of these oscillations. These data
      demonstrate that alpha2M* and LRP1 modulate the BKCachannel in human myometrium
      and that BKCaand its immunomodulatory interacting partners regulate
      Ca(2+)dynamics in hMSMCs during pregnancy. 

PMID- 27044075
TI  - Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane
      contact sites.
AB  - Organelles are in constant communication with each other through exchange of
      proteins (mediated by trafficking vesicles) and lipids [mediated by both
      trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known
      that vesicle trafficking can be tightly regulated by the second messenger Ca(2+),
      allowing membrane protein transport to be adjusted according to physiological
      demands. However, it remains unclear whether LTP-mediated lipid transport can
      also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E
      Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma
      membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and
      endogenous mammalian proteins, we discovered that E-Syts transfer
      glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts
      use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding
      protein (SMP) domains to transfer lipids. However, the SMP domains themselves
      cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)
      bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E
      Syts was fully recapitulated when the SMP domain was fused to the cytosolic
      domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion,
      indicating that a common mechanism of membrane tethering governs the
      Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that
      microsomal vesicles isolated from mammalian cells contained robust Ca(2+)
      dependent lipid transfer activities, which were mediated by E-Syts. These
      findings established E-Syts as a novel class of LTPs and showed that LTP-mediated
      lipid trafficking, like vesicular transport, can be subject to tight
      Ca(2+)regulation. 

PMID- 27044076
TI  - Cellular uptake and anticancer activity of carboxylated gallium corroles.
AB  - We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1
      [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic
      ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated
      high cytotoxic activity against all NCI60 cell lines derived from nine tumor
      types and confirmed very high toxicity against melanoma cells, specifically the
      LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)]
      toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian
      (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50values
      ranged from 4.8 to >200 uM; and they correlated with the rates of uptake, extent
      of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4,
      which exhibited about 10-fold lower IC50values (<20 uM) relative to previous
      analogs against all four cancer cell lines, displayed high efficacy (Emax= 0).
      Confocal fluorescence imaging revealed facile uptake of functionalized gallium
      corroles by all human cancer cells that followed the order: 4 >> 3 > 2 >> 1
      (intracellular accumulation of gallium corroles was fastest in melanoma cells).
      We conclude that carboxylated gallium corroles are promising chemotherapeutics
      with the advantage that they also can be used for tumor imaging. 

PMID- 27044077
TI  - PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue
      regenerative multipotent stem cells.
AB  - Current approaches in tissue engineering are geared toward generating tissue
      specific stem cells. Given the complexity and heterogeneity of tissues, this
      approach has its limitations. An alternate approach is to induce terminally
      differentiated cells to dedifferentiate into multipotent proliferative cells with
      the capacity to regenerate all components of a damaged tissue, a phenomenon used
      by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog
      that is used to treat preleukemic and leukemic blood disorders. AZA is also known
      to induce cell plasticity. We hypothesized that AZA-induced cell plasticity
      occurs via a transient multipotent cell state and that concomitant exposure to a
      receptive growth factor might result in the expansion of a plastic and
      proliferative population of cells. To this end, we treated lineage-committed
      cells with AZA and screened a number of different growth factors with known
      activity in mesenchyme-derived tissues. Here, we report that transient treatment
      with AZA in combination with platelet-derived growth factor-AB converts primary
      somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells
      possess a distinct transcriptome, are immunosuppressive, and demonstrate long
      term self-renewal, serial clonogenicity, and multigerm layer differentiation
      potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute
      directly to in vivo tissue regeneration in a context-dependent manner and, unlike
      embryonic or pluripotent stem cells, do not form teratomas. Taken together, this
      vector-free method of generating iMS cells from primary terminally differentiated
      cells has significant scope for application in tissue regeneration. 

PMID- 27044078
TI  - Long antibody HCDR3s from HIV-naive donors presented on a PG9 neutralizing
      antibody background mediate HIV neutralization.
AB  - Development of broadly neutralizing antibodies (bnAbs) against HIV-1 usually
      requires prolonged infection and induction of Abs with unusual features, such as
      long heavy-chain complementarity-determining region 3 (HCDR3) loops. Here we
      sought to determine whether the repertoires of HIV-1-naive individuals contain
      Abs with long HCDR3 loops that could mediate HIV-1 neutralization. We
      interrogated at massive scale the structural properties of long Ab HCDR3 loops in
      HIV-1-naive donors, searching for structured HCDR3s similar to those of the HIV-1
      bnAb PG9. We determined the nucleotide sequences encoding 2.3 * 10(7)unique HCDR3
      amino acid regions from 70 different HIV-1-naive donors. Of the 26,917 HCDR3
      loops with 30-amino acid length identified, we tested 30 for further study that
      were predicted to have PG9-like structure when chimerized onto PG9. Three of
      these 30 PG9 chimeras bound to the HIV-1 gp120 monomer, and two were
      neutralizing. In addition, we found 14 naturally occurring HCDR3 sequences that
      acquired the ability to bind to the HIV-1 gp120 monomer when adding 2- to 7-amino
      acid mutations via computational design. Of those 14 designed Abs, 8 neutralized
      HIV-1, with IC50values ranging from 0.7 to 98 ug/mL. These data suggest that the
      repertoire of HIV-1-naive individuals contains rare B cells that encode HCDR3
      loops that bind or neutralize HIV-1 when presented on a PG9 background with
      relatively few or no additional mutations. Long HCDR3 sequences are present in
      the HIV-naive B-cell repertoire, suggesting that this class of bnAbs is a
      favorable target for rationally designed preventative vaccine efforts. 

PMID- 27044079
TI  - Pathogen receptor discovery with a microfluidic human membrane protein array.
AB  - The discovery of how a pathogen invades a cell requires one to determine which
      host cell receptors are exploited. This determination is a challenging problem
      because the receptor is invariably a membrane protein, which represents an
      Achilles heel in proteomics. We have developed a universal platform for high
      throughput expression and interaction studies of membrane proteins by creating a
      microfluidic-based comprehensive human membrane protein array (MPA). The MPA is,
      to our knowledge, the first of its kind and offers a powerful alternative to
      conventional proteomics by enabling the simultaneous study of 2,100 membrane
      proteins. We characterized direct interactions of a whole nonenveloped virus
      (simian virus 40), as well as those of the hepatitis delta enveloped virus large
      form antigen, with candidate host receptors expressed on the MPA. Selected newly
      discovered membrane protein-pathogen interactions were validated by conventional
      methods, demonstrating that the MPA is an important tool for cellular receptor
      discovery and for understanding pathogen tropism. 

PMID- 27044080
TI  - The effect of gene interactions on the long-term response to selection.
AB  - The role of gene interactions in the evolutionary process has long been
      controversial. Although some argue that they are not of importance, because most
      variation is additive, others claim that their effect in the long term can be
      substantial. Here, we focus on the long-term effects of genetic interactions
      under directional selection assuming no mutation or dominance, and that epistasis
      is symmetrical overall. We ask by how much the mean of a complex trait can be
      increased by selection and analyze two extreme regimes, in which either drift or
      selection dominate the dynamics of allele frequencies. In both scenarios,
      epistatic interactions affect the long-term response to selection by modulating
      the additive genetic variance. When drift dominates, we extend Robertson's
      [Robertson A (1960)Proc R Soc Lond B Biol Sci153(951):234-249] argument to show
      that, for any form of epistasis, the total response of a haploid population is
      proportional to the initial total genotypic variance. In contrast, the total
      response of a diploid population is increased by epistasis, for a given initial
      genotypic variance. When selection dominates, we show that the total selection
      response can only be increased by epistasis when some initially deleterious
      alleles become favored as the genetic background changes. We find a simple
      approximation for this effect and show that, in this regime, it is the structure
      of the genotype-phenotype map that matters and not the variance components of the
      population. 

PMID- 27044081
TI  - Hall effect in quantum critical charge-cluster glass.
AB  - Upon doping, cuprates undergo a quantum phase transition from an insulator to a d
      wave superconductor. The nature of this transition and of the insulating state is
      vividly debated. Here, we study the Hall effect in La2-xSrxCuO4(LSCO) samples
      doped near the quantum critical point atx~ 0.06. Dramatic fluctuations in the
      Hall resistance appear belowTCG~ 1.5 K and increase as the sample is cooled down
      further, signaling quantum critical behavior. We explore the doping dependence of
      this effect in detail, by studying a combinatorial LSCO library in which the Sr
      content is varied in extremely fine steps,Deltax~ 0.00008. We observe that
      quantum charge fluctuations wash out when superconductivity emerges but can be
      restored when the latter is suppressed by applying a magnetic field, showing that
      the two instabilities compete for the ground state. 

PMID- 27044082
TI  - Population size does not explain past changes in cultural complexity.
AB  - Demography is increasingly being invoked to account for features of the
      archaeological record, such as the technological conservatism of the Lower and
      Middle Pleistocene, the Middle to Upper Paleolithic transition, and cultural loss
      in Holocene Tasmania. Such explanations are commonly justified in relation to
      population dynamic models developed by Henrich [Henrich J (2004)Am Antiq69:197
      214] and Powell et al. [Powell A, et al. (2009)Science324(5932):1298-1301], which
      appear to demonstrate that population size is the crucial determinant of cultural
      complexity. Here, we show that these models fail in two important respects.
      First, they only support a relationship between demography and culture in
      implausible conditions. Second, their predictions conflict with the available
      archaeological and ethnographic evidence. We conclude that new theoretical and
      empirical research is required to identify the factors that drove the changes in
      cultural complexity that are documented by the archaeological record. 

PMID- 27044083
TI  - Species interactions slow warming-induced upward shifts of treelines on the
      Tibetan Plateau.
AB  - The alpine treeline is commonly regarded as being sensitive to climatic warming
      because regeneration and growth of trees at treeline generally are limited by low
      temperature. The alpine treelines of the Tibetan Plateau (TP) occur at the
      highest elevations (4,900 m above sea level) in the Northern Hemisphere. Ongoing
      climatic warming is expected to shift treelines upward. Studies of treeline
      dynamics at regional and local scales, however, have yielded conflicting results,
      indicating either unchanging treeline elevations or upward shifts. To reconcile
      this conflict, we reconstructed in detail a century of treeline structure and
      tree recruitment at sites along a climatic gradient of 4  degrees C and mean
      annual rainfall of 650 mm on the eastern TP. Species interactions interacted with
      effects of warming on treeline and could outweigh them. Densification of shrubs
      just above treeline inhibited tree establishment, and slowed upward movement of
      treelines on a time scale of decades. Interspecific interactions are major
      processes controlling treeline dynamics that may account for the absence of an
      upward shift at some TP treelines despite continued climatic warming. 

PMID- 27044084
TI  - Mechanism for accurate, protein-assisted DNA annealing by Deinococcus radiodurans
      DdrB.
AB  - Accurate pairing of DNA strands is essential for repair of DNA double-strand
      breaks (DSBs). How cells achieve accurate annealing when large regions of single
      strand DNA are unpaired has remained unclear despite many efforts focused on
      understanding proteins, which mediate this process. Here we report the crystal
      structure of a single-strand annealing protein [DdrB (DNA damage response B)] in
      complex with a partially annealed DNA intermediate to 2.2 A. This structure and
      supporting biochemical data reveal a mechanism for accurate annealing involving
      DdrB-mediated proofreading of strand complementarity. DdrB promotes high-fidelity
      annealing by constraining specific bases from unauthorized association and only
      releases annealed duplex when bound strands are fully complementary. To our
      knowledge, this mechanism provides the first understanding for how cells achieve
      accurate, protein-assisted strand annealing under biological conditions that
      would otherwise favor misannealing. 

PMID- 27044085
TI  - Functional network inference of the suprachiasmatic nucleus.
AB  - In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators
      communicate within a neuronal network to generate precise system-wide circadian
      rhythms. Although the intracellular genetic oscillator and intercellular
      biochemical coupling mechanisms have been examined previously, the network
      topology driving synchronization of the SCN has not been elucidated. This network
      has been particularly challenging to probe, due to its oscillatory components and
      slow coupling timescale. In this work, we investigated the SCN network at a
      single-cell resolution through a chemically induced desynchronization. We then
      inferred functional connections in the SCN by applying the maximal information
      coefficient statistic to bioluminescence reporter data from individual neurons
      while they resynchronized their circadian cycling. Our results demonstrate that
      the functional network of circadian cells associated with resynchronization has
      small-world characteristics, with a node degree distribution that is exponential.
      We show that hubs of this small-world network are preferentially located in the
      central SCN, with sparsely connected shells surrounding these cores. Finally, we
      used two computational models of circadian neurons to validate our predictions of
      network structure. 

PMID- 27044086
TI  - Polarized localization of voltage-gated Na+ channels is regulated by concerted
      FGF13 and FGF14 action.
AB  - Clustering of voltage-gated sodium channels (VGSCs) within the neuronal axon
      initial segment (AIS) is critical for efficient action potential initiation.
      Although initially inserted into both somatodendritic and axonal membranes, VGSCs
      are concentrated within the axon through mechanisms that include preferential
      axonal targeting and selective somatodendritic endocytosis. How the endocytic
      machinery specifically targets somatic VGSCs is unknown. Here, using knockdown
      strategies, we show that noncanonical FGF13 binds directly to VGSCs in
      hippocampal neurons to limit their somatodendritic surface expression, although
      exerting little effect on VGSCs within the AIS. In contrast, homologous FGF14,
      which is highly concentrated in the proximal axon, binds directly to VGSCs to
      promote their axonal localization. Single-point mutations in FGF13 or FGF14
      abrogating VGSC interaction in vitro cannot support these specific functions in
      neurons. Thus, our data show how the concerted actions of FGF13 and FGF14
      regulate the polarized localization of VGSCs that supports efficient action
      potential initiation.

PMID- 27044087
TI  - Cranial grafting of stem cell-derived microvesicles improves cognition and
      reduces neuropathology in the irradiated brain.
AB  - Cancer survivors face a variety of challenges as they cope with disease
      recurrence and a myriad of normal tissue complications brought on by radio- and
      chemotherapeutic treatment regimens. For patients subjected to cranial
      irradiation for the control of CNS malignancy, progressive and debilitating
      cognitive dysfunction remains a pressing unmet medical need. Although this
      problem has been recognized for decades, few if any satisfactory long-term
      solutions exist to resolve this serious unintended side effect of radiotherapy.
      Past work from our laboratory has demonstrated the neurocognitive benefits of
      human neural stem cell (hNSC) grafting in the irradiated brain, where
      intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive
      deficits. Using a similar strategy, we now provide, to our knowledge, the first
      evidence that cranial grafting of microvesicles secreted from hNSC affords
      similar neuroprotective phenotypes after head-only irradiation. Cortical- and
      hippocampal-based deficits found 1 mo after irradiation were completely resolved
      in animals cranially grafted with microvesicles. Microvesicle treatment was found
      to attenuate neuroinflammation and preserve host neuronal morphology in distinct
      regions of the brain. These data suggest that the neuroprotective properties of
      microvesicles act through a trophic support mechanism that reduces inflammation
      and preserves the structural integrity of the irradiated microenvironment. 

PMID- 27044088
TI  - Insight into GATA1 transcriptional activity through interrogation of cis elements
      disrupted in human erythroid disorders.
AB  - Whole-exome sequencing has been incredibly successful in identifying causal
      genetic variants and has revealed a number of novel genes associated with blood
      and other diseases. One limitation of this approach is that it overlooks
      mutations in noncoding regulatory elements. Furthermore, the mechanisms by which
      mutations in transcriptionalcis-regulatory elements result in disease remain
      poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three
      such elements harboring mutations in human erythroid disorders, which in all
      cases are predicted to disrupt a canonical binding motif for the hematopoietic
      transcription factor GATA1. Deletions of as few as two to four nucleotides
      resulted in a substantial decrease (>80%) in target gene expression. Isolated
      deletions of the canonical GATA1 binding motif completely abrogated binding of
      the cofactor TAL1, which binds to a separate motif. Having verified the
      functionality of these three GATA1 motifs, we demonstrate strong evolutionary
      conservation of GATA1 motifs in regulatory elements proximal to other genes
      implicated in erythroid disorders, and show that targeted disruption of such
      elements results in altered gene expression. By modeling transcription factor
      binding patterns, we show that multiple transcription factors are associated with
      erythroid gene expression, and have created predictive maps modeling putative
      disruptions of their binding sites at key regulatory elements. Our study provides
      insight into GATA1 transcriptional activity and may prove a useful resource for
      investigating the pathogenicity of noncoding variants in human erythroid
      disorders. 

PMID- 27044089
TI  - Potential escalation of heat-related working costs with climate and socioeconomic
      changes in China.
AB  - Global climate change will increase the frequency of hot temperatures, impairing
      health and productivity for millions of working people and raising labor costs.
      In mainland China, high-temperature subsidies (HTSs) are allocated to employees
      for each working day in extremely hot environments, but the potential heat
      related increase in labor cost has not been evaluated so far. Here, we estimate
      the potential HTS cost in current and future climates under different scenarios
      of socioeconomic development and radiative forcing (Representative Concentration
      Pathway), taking uncertainties from the climate model structure and bias
      correction into account. On average, the total HTS in China is estimated at 38.6
      billion yuan/y (US $6.22 billion/y) over the 1979-2005 period, which is
      equivalent to 0.2% of the gross domestic product (GDP). Assuming that the HTS
      standards (per employee per hot day) remain unchanged throughout the 21st
      century, the total HTS may reach 250 billion yuan/y in the 2030s and 1,000
      billion yuan/y in 2100. We further show that, without specific adaptation, the
      increased HTS cost is mainly determined by population growth until the 2030s and
      climate change after the mid-21st century because of increasingly frequent hot
      weather. Accounting for the likely possibility that HTS standards follow the
      wages, the share of GDP devoted to HTS could become as high as 3% at the end of
      21st century. 

PMID- 27044090
TI  - Importance of ocean salinity for climate and habitability.
AB  - Modeling studies of terrestrial extrasolar planetary climates are now including
      the effects of ocean circulation due to a recognition of the importance of oceans
      for climate; indeed, the peak equator-pole ocean heat transport on Earth peaks at
      almost half that of the atmosphere. However, such studies have made the
      assumption that fundamental oceanic properties, such as salinity, temperature,
      and depth, are similar to Earth. This assumption results in Earth-like
      circulations: a meridional overturning with warm water moving poleward at the
      surface, being cooled, sinking at high latitudes, and traveling equatorward at
      depth. Here it is shown that an exoplanetary ocean with a different salinity can
      circulate in the opposite direction: an equatorward flow of polar water at the
      surface, sinking in the tropics, and filling the deep ocean with warm water. This
      alternative flow regime results in a dramatic warming in the polar regions,
      demonstrated here using both a conceptual model and an ocean general circulation
      model. These results highlight the importance of ocean salinity for exoplanetary
      climate and consequent habitability and the need for its consideration in future
      studies. 

PMID- 27044091
TI  - Slow climate velocities of mountain streams portend their role as refugia for
      cold-water biodiversity.
AB  - The imminent demise of montane species is a recurrent theme in the climate change
      literature, particularly for aquatic species that are constrained to networks and
      elevational rather than latitudinal retreat as temperatures increase. Predictions
      of widespread species losses, however, have yet to be fulfilled despite decades
      of climate change, suggesting that trends are much weaker than anticipated and
      may be too subtle for detection given the widespread use of sparse water
      temperature datasets or imprecise surrogates like elevation and air temperature.
      Through application of large water-temperature databases evaluated for
      sensitivity to historical air-temperature variability and computationally
      interpolated to provide high-resolution thermal habitat information for a 222,000
      km network, we estimate a less dire thermal plight for cold-water species within
      mountains of the northwestern United States. Stream warming rates and climate
      velocities were both relatively low for 1968-2011 (average warming rate = 0.101 
      degrees C/decade; median velocity = 1.07 km/decade) when air temperatures warmed
      at 0.21  degrees C/decade. Many cold-water vertebrate species occurred in a
      subset of the network characterized by low climate velocities, and three native
      species of conservation concern occurred in extremely cold, slow velocity
      environments (0.33-0.48 km/decade). Examination of aggressive warming scenarios
      indicated that although network climate velocities could increase, they remain
      low in headwaters because of strong local temperature gradients associated with
      topographic controls. Better information about changing hydrology and disturbance
      regimes is needed to complement these results, but rather than being climatic cul
      de-sacs, many mountain streams appear poised to be redoubts for cold-water
      biodiversity this century. 

PMID- 27044092
TI  - Real-time monitoring of metabolic function in liver-on-chip microdevices tracks
      the dynamics of mitochondrial dysfunction.
AB  - Microfluidic organ-on-a-chip technology aims to replace animal toxicity testing,
      but thus far has demonstrated few advantages over traditional methods.
      Mitochondrial dysfunction plays a critical role in the development of chemical
      and pharmaceutical toxicity, as well as pluripotency and disease processes.
      However, current methods to evaluate mitochondrial activity still rely on end
      point assays, resulting in limited kinetic and prognostic information. Here, we
      present a liver-on-chip device capable of maintaining human tissue for over a
      month in vitro under physiological conditions. Mitochondrial respiration was
      monitored in real time using two-frequency phase modulation of tissue-embedded
      phosphorescent microprobes. A computer-controlled microfluidic switchboard
      allowed contiguous electrochemical measurements of glucose and lactate, providing
      real-time analysis of minute shifts from oxidative phosphorylation to anaerobic
      glycolysis, an early indication of mitochondrial stress. We quantify the dynamics
      of cellular adaptation to mitochondrial damage and the resulting redistribution
      of ATP production during rotenone-induced mitochondrial dysfunction and
      troglitazone (Rezulin)-induced mitochondrial stress. We show troglitazone shifts
      metabolic fluxes at concentrations previously regarded as safe, suggesting a
      mechanism for its observed idiosyncratic effect. Our microfluidic platform
      reveals the dynamics and strategies of cellular adaptation to mitochondrial
      damage, a unique advantage of organ-on-chip technology. 

PMID- 27044093
TI  - Recurrent specialization on a toxic fruit in an island Drosophila population.
AB  - Recurrent specialization on similar host plants offers a unique opportunity to
      unravel the evolutionary and genetic mechanisms underlying dietary shifts. Recent
      studies have focused on ecological races belonging to the same species, but it is
      hard in many cases to untangle the role of adaptive introgression versus distinct
      mutations in facilitating recurrent evolution. We discovered on the island of
      Mayotte a population of the generalist fly Drosophila yakuba that is strictly
      associated with noni (Morinda citrifolia). This case strongly resembles
      Drosophila sechellia, a genetically isolated insular relative of D. yakuba whose
      intensely studied specialization on toxic noni fruits has always been considered
      a unique event in insect evolution. Experiments revealed that unlike mainland D.
      yakuba strains, Mayotte flies showed strong olfactory attraction and significant
      toxin tolerance to noni. Island females strongly discriminated against mainland
      males, suggesting that dietary adaptation has been accompanied by partial
      reproductive isolation. Population genomic analysis indicated a recent
      colonization (~29 kya), at a time when year-round noni fruits may have presented
      a predictable resource on the small island, with ongoing migration after
      colonization. This relatively recent time scale allowed us to search for
      putatively adaptive loci based on genetic variation. Strong signals of genetic
      differentiation were found for several detoxification genes, including a major
      toxin tolerance locus in D. sechellia Our results suggest that recurrent
      evolution on a toxic resource can involve similar historical events and common
      genetic bases, and they establish an important genetic system for the study of
      early stages of ecological specialization and speciation. 

PMID- 27044094
TI  - Culture shapes the evolution of cognition.
AB  - A central debate in cognitive science concerns the nativist hypothesis, the
      proposal that universal features of behavior reflect a biologically determined
      cognitive substrate: For example, linguistic nativism proposes a domain-specific
      faculty of language that strongly constrains which languages can be learned. An
      evolutionary stance appears to provide support for linguistic nativism, because
      coordinated constraints on variation may facilitate communication and therefore
      be adaptive. However, language, like many other human behaviors, is underpinned
      by social learning and cultural transmission alongside biological evolution. We
      set out two models of these interactions, which show how culture can facilitate
      rapid biological adaptation yet rule out strong nativization. The amplifying
      effects of culture can allow weak cognitive biases to have significant population
      level consequences, radically increasing the evolvability of weak, defeasible
      inductive biases; however, the emergence of a strong cultural universal does not
      imply, nor lead to, nor require, strong innate constraints. From this we must
      conclude, on evolutionary grounds, that the strong nativist hypothesis for
      language is false. More generally, because such reciprocal interactions between
      cultural and biological evolution are not limited to language, nativist
      explanations for many behaviors should be reconsidered: Evolutionary reasoning
      shows how we can have cognitively driven behavioral universals and yet extreme
      plasticity at the level of the individual-if, and only if, we account for the
      human capacity to transmit knowledge culturally. Wherever culture is involved,
      weak cognitive biases rather than strong innate constraints should be the default
      assumption. 

PMID- 27044095
TI  - Nuclear transfer nTreg model reveals fate-determining TCR-beta and novel
      peripheral nTreg precursors.
AB  - To study the development and function of "natural-arising" T regulatory (nTreg)
      cells, we developed a novel nTreg model on pure nonobese diabetic background
      using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1
      deficient background, we found that monoclonal FoxP3(+)CD4(+)Treg cells developed
      in the thymus in the absence of other T cells. Adoptive transfer experiments
      revealed that the thymic niche is not a limiting factor in nTreg development. In
      addition, we showed that the T-cell receptor (TCR) beta-chain of our nTreg model
      was not only sufficient to bias T-cell development toward the CD4 lineage, but we
      also demonstrated that this TCR beta-chain was able to provide stronger TCR
      signals. This TCR-beta-driven mechanism would thus unify former per se
      contradicting hypotheses of TCR-dependent and -independent nTreg development.
      Strikingly, peripheral FoxP3(-)CD4(+)T cells expressing the same TCR as this
      somatic cell nuclear transfer nTreg model had a reduced capability to
      differentiate into Th1 cells but were poised to differentiate better into induced
      nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor
      subset of nTreg cells to which we refer to as pre-nTreg cells. 

PMID- 27044096
TI  - Test of the invasive pathogen hypothesis of bumble bee decline in North America.
AB  - Emergent fungal diseases are critical factors in global biodiversity declines.
      The fungal pathogenNosema bombiwas recently found to be widespread in declining
      species of North American bumble bees (Bombus), with circumstantial evidence
      suggesting an exotic introduction from Europe. This interpretation has been
      hampered by a lack of knowledge of global genetic variation, geographic origin,
      and changing prevalence patterns ofN. bombiin declining North American
      populations. Thus, the temporal and spatial emergence ofN. bombiand its potential
      role in bumble bee decline remain speculative. We analyzeNosemaprevalence and
      genetic variation in the United States and Europe from 1980, before an alleged
      introduction in the early 1990s, to 2011, extractingNosemaDNA fromBombusnatural
      history collection specimens from across this time period.Nosema bombiprevalence
      increased significantly from low detectable frequency in the 1980s to
      significantly higher frequency in the mid- to late-1990s, corresponding to a
      period of reported massive infectious outbreak ofN. bombiin commercial bumble bee
      rearing stocks in North America. Despite the increased frequency, we find no
      conclusive evidence of an exoticN. bombiorigin based on genetic analysis of
      globalNosemapopulations; the widespreadNosemastrain found currently in declining
      United States bumble bees was present in the United States before commercial
      colony trade. Notably, the USN. bombiis not detectably different from that found
      predominantly throughout Western Europe, with both regions characterized by low
      genetic diversity compared with high levels of diversity found in Asia, where
      commercial bee breeding activities are low or nonexistent. 

PMID- 27044097
TI  - Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and
      prolongs survival in glioblastoma by altering macrophages.
AB  - Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We
      previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2)
      compromises the benefits of anti-VEGF receptor (VEGFR) treatment in murine GBM
      models and that circulating Ang-2 levels in GBM patients rebound after an initial
      decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor)
      administration. Here we tested whether dual inhibition of VEGFR/Ang-2 could
      improve survival in two orthotopic models of GBM, Gl261 and U87. Dual therapy
      using cediranib and MEDI3617 (an anti-Ang-2-neutralizing antibody) improved
      survival over each therapy alone by delaying Gl261 growth and increasing U87
      necrosis, effectively reducing viable tumor burden. Consistent with their
      vascular-modulating function, the dual therapies enhanced morphological
      normalization of vessels. Dual therapy also led to changes in tumor-associated
      macrophages (TAMs). Inhibition of TAM recruitment using an anti-colony
      stimulating factor-1 antibody compromised the survival benefit of dual therapy.
      Thus, dual inhibition of VEGFR/Ang-2 prolongs survival in preclinical GBM models
      by reducing tumor burden, improving normalization, and altering TAMs. This
      approach may represent a potential therapeutic strategy to overcome the
      limitations of anti-VEGFR monotherapy in GBM patients by integrating the
      complementary effects of anti-Ang2 treatment on vessels and immune cells. 

PMID- 27044098
TI  - Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to
      anti-tumor phenotype and prolongs glioblastoma survival.
AB  - Inhibition of the vascular endothelial growth factor (VEGF) pathway has failed to
      improve overall survival of patients with glioblastoma (GBM). We previously
      showed that angiopoietin-2 (Ang-2) overexpression compromised the benefit from
      anti-VEGF therapy in a preclinical GBM model. Here we investigated whether dual
      Ang-2/VEGF inhibition could overcome resistance to anti-VEGF treatment. We
      treated mice bearing orthotopic syngeneic (Gl261) GBMs or human (MGG8) GBM
      xenografts with antibodies inhibiting VEGF (B20), or Ang-2/VEGF (CrossMab, A2V).
      We examined the effects of treatment on the tumor vasculature, immune cell
      populations, tumor growth, and survival in both the Gl261 and MGG8 tumor models.
      We found that in the Gl261 model, which displays a highly abnormal tumor
      vasculature, A2V decreased vessel density, delayed tumor growth, and prolonged
      survival compared with B20. In the MGG8 model, which displays a low degree of
      vessel abnormality, A2V induced no significant changes in the tumor vasculature
      but still prolonged survival. In both the Gl261 and MGG8 models A2V reprogrammed
      protumor M2 macrophages toward the antitumor M1 phenotype. Our findings indicate
      that A2V may prolong survival in mice with GBM by reprogramming the tumor immune
      microenvironment and delaying tumor growth. 

PMID- 27044099
TI  - Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate
      metabolism at ER-PM and ER-Golgi junctions.
AB  - Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex
      craniofacial, dental, cutaneous, and limb abnormalities combined with
      intellectual disability. Mutations in thePTDSS1gene coding one of the
      phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in
      LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS
      levels. Here we show that expression of mutant PSS1 enzymes decreased
      phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma
      membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the
      PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM,
      blocked PS synthesis and reduced PS levels by 50% in normal cells. However,
      mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol
      binding protein-related protein 8, which was recently identified as a PI4P-PS
      exchanger between the ER and PM, showed PI4P-dependent membrane association that
      was significantly decreased by expression of PSS1 mutant enzymes. Our studies
      reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from
      the ER. Consequently, PSS1 mutations not only affect cellular PS levels and
      distribution but also lead to a more complex imbalance in lipid homeostasis by
      disturbing PI4P metabolism. 

PMID- 27044100
TI  - Accumulation of formamide in hydrothermal pores to form prebiotic nucleobases.
AB  - Formamide is one of the important compounds from which prebiotic molecules can be
      synthesized, provided that its concentration is sufficiently high. For
      nucleotides and short DNA strands, it has been shown that a high degree of
      accumulation in hydrothermal pores occurs, so that temperature gradients might
      play a role in the origin of life [Baaske P, et al. (2007)Proc Natl Acad Sci
      USA104(22):9346-9351]. We show that the same combination of thermophoresis and
      convection in hydrothermal pores leads to accumulation of formamide up to
      concentrations where nucleobases are formed. The thermophoretic properties of
      aqueous formamide solutions are studied by means of Infrared Thermal Diffusion
      Forced Rayleigh Scattering. These data are used in numerical finite element
      calculations in hydrothermal pores for various initial concentrations, ambient
      temperatures, and pore sizes. The high degree of formamide accumulation is due to
      an unusual temperature and concentration dependence of the thermophoretic
      behavior of formamide. The accumulation fold in part of the pores increases
      strongly with increasing aspect ratio of the pores, and saturates to highly
      concentrated aqueous formamide solutions of ~85 wt% at large aspect ratios. Time
      dependent studies show that these high concentrations are reached after 45-90 d,
      starting with an initial formamide weight fraction of[Formula: see text]wt % that
      is typical for concentrations in shallow lakes on early Earth. 

PMID- 27044101
TI  - Kinetic selection vs. free energy of DNA base pairing in control of polymerase
      fidelity.
AB  - What is the free energy source enabling high-fidelity DNA polymerases (pols) to
      favor incorporation of correct over incorrect base pairs by 10(3)- to 10(4)-fold,
      corresponding to free energy differences of DeltaDeltaGinc~ 5.5-7 kcal/mol?
      Standard DeltaDeltaG degrees  values (~0.3 kcal/mol) calculated from melting
      temperature measurements comparing matched vs. mismatched base pairs at duplex
      DNA termini are far too low to explain pol accuracy. Earlier analyses suggested
      that pol active-site steric constraints can amplify DNA free energy differences
      at the transition state (kinetic selection). A recent paper [Olson et al. (2013)J
      Am Chem Soc135:1205-1208] used Vent pol to catalyze incorporations in the
      presence of inorganic pyrophosphate intended to equilibrate forward
      (polymerization) and backward (pyrophosphorolysis) reactions. A steady-state
      leveling off of incorporation profiles at long reaction times was interpreted as
      reaching equilibrium between polymerization and pyrophosphorolysis, yielding
      apparent DeltaG degrees  = -RTlnKeq, indicating DeltaDeltaG degrees  of 3.5-7
      kcal/mol, sufficient to account for pol accuracy without need of kinetic
      selection. Here we perform experiments to measure and account for
      pyrophosphorolysis explicitly. We show that forward and reverse reactions attain
      steady states far from equilibrium for wrong incorporations such as G opposite T.
      Therefore,[Formula: see text]values obtained from such steady-state evaluations
      ofKeqare not dependent on DNA properties alone, but depend largely on constraints
      imposed on right and wrong substrates in the polymerase active site. 

PMID- 27044102
TI  - The quantum needle of the avian magnetic compass.
AB  - Migratory birds have a light-dependent magnetic compass, the mechanism of which
      is thought to involve radical pairs formed photochemically in cryptochrome
      proteins in the retina. Theoretical descriptions of this compass have thus far
      been unable to account for the high precision with which birds are able to detect
      the direction of the Earth's magnetic field. Here we use coherent spin dynamics
      simulations to explore the behavior of realistic models of cryptochrome-based
      radical pairs. We show that when the spin coherence persists for longer than a
      few microseconds, the output of the sensor contains a sharp feature, referred to
      as a spike. The spike arises from avoided crossings of the quantum mechanical
      spin energy-levels of radicals formed in cryptochromes. Such a feature could
      deliver a heading precision sufficient to explain the navigational behavior of
      migratory birds in the wild. Our results (i) afford new insights into radical
      pair magnetoreception, (ii) suggest ways in which the performance of the compass
      could have been optimized by evolution, (iii) may provide the beginnings of an
      explanation for the magnetic disorientation of migratory birds exposed to
      anthropogenic electromagnetic noise, and (iv) suggest that radical pair
      magnetoreception may be more of a quantum biology phenomenon than previously
      realized. 

PMID- 27044103
TI  - Tiny individuals attached to a new Silurian arthropod suggest a unique mode of
      brood care.
AB  - The ~430-My-old Herefordshire, United Kingdom, Lagerstatte has yielded a
      diversity of remarkably preserved invertebrates, many of which provide
      fundamental insights into the evolutionary history and ecology of particular
      taxa. Here we report a new arthropod with 10 tiny arthropods tethered to its
      tergites by long individual threads. The head of the host, which is covered by a
      shield that projects anteriorly, bears a long stout uniramous antenna and a
      chelate limb followed by two biramous appendages. The trunk comprises 11
      segments, all bearing limbs and covered by tergites with long slender lateral
      spines. A short telson bears long parallel cerci. Our phylogenetic analysis
      resolves the new arthropod as a stem-group mandibulate. The evidence suggests
      that the tethered individuals are juveniles and the association represents a
      complex brooding behavior. Alternative possibilities-that the tethered
      individuals represent a different epizoic or parasitic arthropod-appear less
      likely. 

PMID- 27044104
TI  - Monoclonal antibody therapy for Junin virus infection.
AB  - Countermeasures against potential biothreat agents remain important to US
      Homeland Security, and many of these pharmaceuticals could have dual use in the
      improvement of global public health. Junin virus, the causative agent of
      Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A
      high-priority agent. There are no Food and Drug Administration (FDA) approved
      drugs available for preventing or treating AHF, and the current treatment option
      is limited to administration of immune plasma. Whereas immune plasma demonstrates
      the feasibility of passive immunotherapy, it is limited in quantity, variable in
      quality, and poses safety risks such as transmission of transfusion-borne
      diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative
      to plasma, three previously described neutralizing murine mAbs were expressed as
      mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF.
      These mAbs provided 100% protection against lethal challenge when administered 2
      d after infection (dpi), and one of them (J199) was capable of providing 100%
      protection when treatment was initiated 6 dpi and 92% protection when initiated 7
      dpi. The efficacy of J199 is superior to that previously described for all other
      evaluated drugs, and its high potency suggests that mAbs like J199 offer an
      economical alternative to immune plasma and an effective dual use
      (bioterrorism/public health) therapeutic. 

PMID- 27044105
TI  - Interallelic interaction and gene regulation in budding yeast.
AB  - InDrosophila, homologous chromosome pairing leads to "transvection," in which the
      enhancer of a gene can regulate the allelic transcription intrans.Interallelic
      interactions were also observed in vegetative diploid budding yeast, but their
      functional significance is unknown. Here, we show that aGAL1reporter can interact
      with its homologous allele and affect its expression. By ectopically inserting
      two allelic reporters, one driven by wild-typeGAL1promoter (WTGAL1pr) and the
      other by a mutant promoter with delayed response to galactose induction, we found
      that the two reporters physically associate, and the WTGAL1prtriggers
      synchronized firing of the defective promoter and accelerates its activation
      without affecting its steady-state expression level. This interaction and the
      transregulatory effect disappear when the same reporters are located at
      nonallelic sites. We further demonstrated that the activator Gal4 is essential
      for the interallelic interaction, and the transregulation requires fully
      activated WTGAL1prtranscription. The mechanism of this phenomenon was further
      discussed. Taken together, our data revealed the existence of interallelic gene
      regulation in yeast, which serves as a starting point for understanding long
      distance gene regulation in this genetically tractable system. 

PMID- 27044106
TI  - Tradeoffs between fisheries harvest and the resilience of coral reefs.
AB  - Many countries are legally obliged to embrace ecosystem-based approaches to
      fisheries management. Reductions in bycatch and physical habitat damage are now
      commonplace, but mitigating more sophisticated impacts associated with the
      ecological functions of target fisheries species are in their infancy. Here we
      model the impacts of a parrotfish fishery on the future state and resilience of
      Caribbean coral reefs, enabling us to view the tradeoff between harvest and
      ecosystem health. We find that the implementation of a simple and enforceable
      size restriction of >30 cm provides a win:win outcome in the short term,
      delivering both ecological and fisheries benefits and leading to increased yield
      and greater coral recovery rate for a given harvest rate. However, maintaining
      resilient coral reefs even until 2030 requires the addition of harvest
      limitations (<10% of virgin fishable biomass) to cope with a changing climate and
      induced coral disturbances, even in reefs that are relatively healthy today.
      Managing parrotfish is not a panacea for protecting coral reefs but can play a
      role in sustaining the health of reefs and high-quality habitat for reef
      fisheries. 

PMID- 27044107
TI  - Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an
      extracellular niche to initiate bladder stone formation.
AB  - The catheter-associated uropathogenProteus mirabilisfrequently causes urinary
      stones, but little has been known about the initial stages of bladder
      colonization and stone formation. We found thatP. mirabilisrapidly invades the
      bladder urothelium, but generally fails to establish an intracellular niche.
      Instead, it forms extracellular clusters in the bladder lumen, which form foci of
      mineral deposition consistent with development of urinary stones. These clusters
      elicit a robust neutrophil response, and we present evidence of neutrophil
      extracellular trap generation during experimental urinary tract infection. We
      identified two virulence factors required for cluster development: urease, which
      is required for urolithiasis, and mannose-resistantProteus-like fimbriae. The
      extracellular cluster formation byP. mirabilisstands in direct contrast to
      uropathogenicEscherichia coli, which readily formed intracellular bacterial
      communities but not luminal clusters or urinary stones. We propose that
      extracellular clusters are a key mechanism ofP. mirabilissurvival and virulence
      in the bladder. 

PMID- 27044108
TI  - Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage
      mRNA translation.
AB  - Neutrophils are the first and most numerous cells to arrive at the site of an
      inflammatory insult and are among the first to die. We previously reported that
      alpha defensins, released from apoptotic human neutrophils, augmented the
      antimicrobial capacity of macrophages while also inhibiting the biosynthesis of
      proinflammatory cytokines. In vivo, alpha defensin administration protected mice
      from inflammation, induced by thioglychollate-induced peritonitis or following
      infection withSalmonella entericaserovar Typhimurium. We have now dissected the
      antiinflammatory mechanism of action of the most abundant neutrophil alpha
      defensin, Human Neutrophil Peptide 1 (HNP1). Herein we show that HNP1 enters
      macrophages and inhibits protein translation without inducing the unfolded
      protein response or affecting mRNA stability. In a cell-free in vitro translation
      system, HNP1 powerfully inhibited both cap-dependent and cap-independent mRNA
      translation while maintaining mRNA polysomal association. This is, to our
      knowledge, the first demonstration of a peptide released from one cell type
      (neutrophils) directly regulating mRNA translation in another (macrophages). By
      preventing protein translation, HNP1 functions as a "molecular brake" on
      macrophage-driven inflammation, ensuring both pathogen clearance and the
      resolution of inflammation with minimal bystander tissue damage. 

PMID- 27044109
TI  - Ancestral genetic diversity associated with the rapid spread of stress-tolerant
      coral symbionts in response to Holocene climate change.
AB  - Coral communities in the Persian/Arabian Gulf (PAG) withstand unusually high
      salinity levels and regular summer temperature maxima of up to ~35  degrees C
      that kill conspecifics elsewhere. Due to the recent formation of the PAG and its
      subsequent shift to a hot climate, these corals have had only <6,000 y to adapt
      to these extreme conditions and can therefore inform on how coral reefs may
      respond to global warming. One key to coral survival in the world's warmest reefs
      are symbioses with a newly discovered alga,Symbiodinium thermophilum Currently,
      it is unknown whether this symbiont originated elsewhere or emerged from
      unexpectedly fast evolution catalyzed by the extreme environment. Analyzing
      genetic diversity of symbiotic algae across >5,000 km of the PAG, the Gulf of
      Oman, and the Red Sea coastline, we show thatS. thermophilumis a member of a
      highly diverse, ancient group of symbionts cryptically distributed outside the
      PAG. We argue that the adjustment to temperature extremes by PAG corals was
      facilitated by the positive selection of preadapted symbionts. Our findings
      suggest that maintaining the largest possible pool of potentially stress-tolerant
      genotypes by protecting existing biodiversity is crucial to promote rapid
      adaptation to present-day climate change, not only for coral reefs, but for
      ecosystems in general. 

PMID- 27044110
TI  - Mass-tag labeling reveals site-specific and endogenous levels of protein S-fatty
      acylation.
AB  - Fatty acylation of cysteine residues provides spatial and temporal control of
      protein function in cells and regulates important biological pathways in
      eukaryotes. Although recent methods have improved the detection and proteomic
      analysis of cysteine fatty (S-fatty) acylated proteins, understanding how
      specific sites and quantitative levels of this posttranslational modification
      modulate cellular pathways are still challenging. To analyze the endogenous
      levels of protein S-fatty acylation in cells, we developed a mass-tag labeling
      method based on hydroxylamine-sensitivity of thioesters and selective maleimide
      modification of cysteines, termed acyl-PEG exchange (APE). We demonstrate that
      APE enables sensitive detection of protein S-acylation levels and is broadly
      applicable to different classes of S-palmitoylated membrane proteins. Using APE,
      we show that endogenous interferon-induced transmembrane protein 3 is S-fatty
      acylated on three cysteine residues and site-specific modification of highly
      conserved cysteines are crucial for the antiviral activity of this IFN-stimulated
      immune effector. APE therefore provides a general and sensitive method for
      analyzing the endogenous levels of protein S-fatty acylation and should
      facilitate quantitative studies of this regulated and dynamic lipid modification
      in biological systems. 

PMID- 27044111
TI  - Why are there no persisting hybrids of humans with Denisovans, Neanderthals, or
      anyone else?

PMID- 27044112
TI  - Myh11-Cre is not limited to peritubular myoid cells and interaction between
      Sertoli and peritubular myoid cells needs investigation.

PMID- 27044113
TI  - Unraveling the dynamics and structure of functionalized self-assembled monolayers
      on gold using 2D IR spectroscopy and MD simulations.
AB  - Functionalized self-assembled monolayers (SAMs) are the focus of ongoing
      investigations because they can be chemically tuned to control their structure
      and dynamics for a wide variety of applications, including electrochemistry,
      catalysis, and as models of biological interfaces. Here we combine reflection 2D
      infrared vibrational echo spectroscopy (R-2D IR) and molecular dynamics
      simulations to determine the relationship between the structures of
      functionalized alkanethiol SAMs on gold surfaces and their underlying molecular
      motions on timescales of tens to hundreds of picoseconds. We find that at higher
      head group density, the monolayers have more disorder in the alkyl chain packing
      and faster dynamics. The dynamics of alkanethiol SAMs on gold are much slower
      than the dynamics of alkylsiloxane SAMs on silica. Using the simulations, we
      assess how the different molecular motions of the alkyl chain monolayers give
      rise to the dynamics observed in the experiments.

PMID- 27044114
TI  - Reply to Chen and Liu: Role of GDNF from peritubular myoid cells in the testis
      stem cell niche.

PMID- 27044115
TI  - Retraction for Dong et al., Deficient Smad7 expression: A putative molecular
      defect in scleroderma.

PMID- 27044117
TI  - Authors' reply.

PMID- 27044116
TI  - Prostate epithelial cell of origin determines cancer differentiation state in an
      organoid transformation assay.
AB  - The cell of origin for prostate cancer remains a subject of debate. Genetically
      engineered mouse models have demonstrated that both basal and luminal cells can
      serve as cells of origin for prostate cancer. Using a human prostate regeneration
      and transformation assay, our group previously demonstrated that basal cells can
      serve as efficient targets for transformation. Recently, a subpopulation of
      multipotent human luminal cells defined by CD26 expression that retains
      progenitor activity in a defined organoid culture was identified. We transduced
      primary human prostate basal and luminal cells with lentiviruses expressing c-Myc
      and activated AKT1 (myristoylated AKT1 or myrAKT1) to mimic theMYCamplification
      andPTENloss commonly detected in human prostate cancer. These cells were
      propagated in organoid culture before being transplanted into immunodeficient
      mice. We found that c-Myc/myrAKT1-transduced luminal xenografts exhibited
      histological features of well-differentiated acinar adenocarcinoma, with strong
      androgen receptor (AR) and prostate-specific antigen (PSA) expression. In
      contrast, c-Myc/myrAKT1-transduced basal xenografts were histologically more
      aggressive, with a loss of acinar structures and low/absent AR and PSA
      expression. Our findings imply that distinct subtypes of prostate cancer may
      arise from luminal and basal epithelial cell types subjected to the same
      oncogenic insults. This study provides a platform for the functional evaluation
      of oncogenes in basal and luminal epithelial populations of the human prostate.
      Tumors derived in this fashion with defined genetics can be used in the
      preclinical development of targeted therapeutics. 

PMID- 27044118
TI  - Administrative Actions for Noncompliance; Lesser Administrative   Actions. Direct
      final rule.
AB  - The Food and Drug Administration (FDA) is amending the regulation describing
      lesser administrative actions that may be imposed on an Institutional Review
      Board (IRB) that has failed to comply with FDA's IRB regulations. We are
      clarifying that FDA may require the IRB to withhold approval of new FDA-regulated
      studies, stop the enrollment of new subjects in ongoing studies, and terminate
      ongoing studies, or any combination of these actions until the noncompliance with
      FDA's IRB regulations is corrected. We are taking this action to ensure clarity
      and improve the accuracy of the regulations.

PMID- 27044120
TI  - Notice of correction.

PMID- 27044119
TI  - Letter From The Editor.

PMID- 27044121
TI  - The Future of Nursing 5 Years Later--Where Are We Now?

PMID- 27044122
TI  - The Land of Oz and Medical-Surgical Nursing Practice.

PMID- 27044123
TI  - Clinical Leadership: A Call to Action.
AB  - Clinical nurses are expected to assume leadership roles to enhance patient care
      and assure efficient work processes. Dimensions of clinical leadership and the
      essential knowledge and skills of the clinical leader are described.

PMID- 27044124
TI  - Implementation of an Evidence-Based Patient Safety Team to Prevent Falls in
      Inpatient Medical Units.
AB  - Falls are a patient safety priority among hospital inpatients. The creation of a
      Patient Safety Team engaged frontline staff in patient safety and falls
      prevention. This intervention decreased the fall rate from 1.90 to 0.69 falls per
      1,000 occupied bed days.

PMID- 27044125
TI  - Fall Risk Associated with Continuous Peripheral Nerve Blocks Following Knee and
      Hip Arthroplasty.
AB  - Combined scientific advances in pharmaceutical agents, perineural blocks, and
      pump delivery capabilities such as those used with continuous peripheral nerve
      blocks have demonstrated advantages in pain management for patients undergoing
      joint arthroplasty. This report documents the incidence of falls increased after
      the implementation of a continuous peripheral nerve block program for patients
      undergoing knee and hip arthroplasty in an academic medical center.

PMID- 27044126
TI  - Improving Nurse-Physician Teamwork: A Multidisciplinary Collaboration.
AB  - Nurses surveyed on an inpatient gynecology surgical unit suggested communication
      and teamwork between nurses and physicians could be improved. To enhance
      teamwork, a multidisciplinary collaboration committee of nurses and physicians
      was created.

PMID- 27044127
TI  - Evaluation of a Nurse-Initiated Routine HIV Testing Pilot on a Medical-Surgical
      Unit.
AB  - National guidelines recommending a shift from risk-based to routine HIV testing
      for persons ages 13-64 are described. The role of nurses, particularly medical
      surgical nurses, in increasing the number of people screened is discussed.

PMID- 27044128
TI  - Peripheral IV Site Rotation Based on Clinical Assessment vs. Length of Time Since
      Insertion.
AB  - The difference in complication rates for phlebitis and infiltration between
      peripheral intravenous site rotation based on clinical assessment versus length
      of time since insertion was evaluated. Evidence was generated for a policy change
      that will impact the quality of patient care.

PMID- 27044129
TI  - Antithyroid Drugs for Hyperthyroidism.
AB  - Hyperthyroidism is a treatable endocrine disorder. Having a working knowledge of
      the current evidence-based guidelines for treating hyperthyroidism aids in
      improved patient care.

PMID- 27044130
TI  - Neurovascular Assessment: An Essential Nursing Focus.

PMID- 27044131
TI  - Fisher's Exact Test.

PMID- 27044132
TI  - Falls Prevention.

PMID- 27044133
TI  - Qualities of Effective Preceptors.

PMID- 27044134
TI  - A Renewed Look at Faith Community Nursing.

PMID- 27044135
TI  - [Intermediate phenotype studies in psychiatric disorder].
AB  - The concept of intermediate phenotype was proposed by Dr. Weinberger of the
      National Institute of Mental Health (NIMH). The risk genes for mental disorders
      define intermediate phenotypes, neurobiological characteristics observed in
      psychiatric disorders, and intermediate phenotypes increase the risk of mental
      disorders. The author worked at Dr. Weinberger's laboratory, and after returning
      home, introduced the concept to Japan, creating a term "Chukanhyogengata" to
      translate "intermediate phenotype". Intermediate phenotype has been proposed as a
      tool for the identification of risk genes for mental disorders, spreading the
      concept as a biomarker for the bridging between genes and behaviors. Intermediate
      phenotype studies later became one of the main pillars of psychiatric research.
      As a large number of data and samples are needed for intermediate phenotype
      research, we built a research resource database that combines the brain phenotype
      and bioresources. We performed genome-wide association analysis of cognitive
      decline in schizophrenia and identified the DEGS2 gene using this sample. This
      research resource database was developed for a multicenter study by COCORO
      (Cognitive Genetics Collaborative Research Organization). COCORO carried out
      genome-wide association analysis of the gray matter volume of the superior
      temporal gyrus and identified genome-wide significant loci. In this paper, we
      introduce the concept and history of intermediate phenotype study of mental
      illness and the latest trends. We hope to contribute to the future development of
      mental illness research through translational research.

PMID- 27044136
TI  - Bioactive Lipids Safeguard Our Brain from Various Challenges.
AB  - The bioactive lipids plasmalogens (Pls), especially the ethanolamine types,
      PlsEtn, are found to be enriched in the central nervous system (CNS). Previous
      reports showed that the brain and serum Pls levels were reduced in Alzheimer's
      disease (AD). However, the role of the Pls in AD is mostly elusive. Furthermore
      Pls have been suggested to have pathophysiological significance in ageing and
      stress responses in the CNS, which often involve neuroinflammation characterized
      by glial cell activation. Focusing on these lipids function in the murine brain,
      we first show that Pls can ameliorate microglial activation induced by systemic
      inflammatory stimuli. Then their protective effects on the neuronal cell death
      are demonstrated. The precise mechanism of how these lipids function in the brain
      is now under investigation but our study will reveal the myth of these crucial
      lipid components in the CNS. Future study also could suggest novel therapeutics
      to safeguard our brain from various stresses including ageing, neuroinflammation
      as well as the memory disturbance in AD.

PMID- 27044137
TI  - [Infection Control Effect of Dietary Fluid with Whey Peptide in the Management of
      Patients with Severe Intracranial Hemorrhage During the Acute Stage].
AB  - Abstract BACKGROUND AND PURPOSE: Patients with severe intracranial hemorrhage
      (ICH) often develop infectious complications during the acute stage. Animal
      experiments have demonstrated that enteral immunonutrition with a dietary fluid
      containing whey peptide (WP) enhances immunoactivity and prevents infection. The
      aim of the current study was to investigate the infection control effect of WP in
      the clinical management of patients with severe ICH. METHODS: Fourteen patients
      with ICH were given enteral nutrition from January 2012 to December 2012. Nine
      patients were given WP (WP group) and the other five were given control dietary
      fluid (Non-WP group) for two weeks. We retrospectively analyzed the incidence of
      infectious complications and chronological changes in white blood cell (WBC)
      count, C-reactive protein (CRP), and total lymphocyte count. RESULTS: All
      patients in the Non-WP Group experienced infectious complications, whereas 5 out
      of 9 patients in the WP Group did not experience them. There was a tendency for a
      decrease in WBC count and CRP value in the WP group. In contrast, WBC and CRP
      increased in 3 patients in the Non-WP Group. Total lymphocyte count tended to
      increase earlier in the WP Group; however this tendency was not noted in the Non
      WP Group. CONCLUSION: Although the number of cases was small, our study suggests
      that WP might have an infection control effect, capable of preventing infectious
      complications associated with severe ICH in the acute stage.

PMID- 27044138
TI  - [Effects of Mental Disorders on the Academic Outcomes of University Students--A
      Retrospective Study Using Medical Records from a Health Services Center].
AB  - OBJECTIVE: Falling behind in class is a serious problem for university students
      as it can lead to social problems and increase the risk of suicide. Although it
      is common for students suffering from mental disorders to fall behind
      academically, there have been few studies investigating the difficulties these
      students face in order to graduate from university. Therefore, we investigated
      factors associated with dropping out of school with the purpose of creating a
      strategy to improve the academic outcomes of students who regularly seek
      psychiatric consultation. SUBJECTS: We investigated undergraduate students who
      received consultation at Tsukuba University's Health Services Center Psychiatry
      Department and whose academic outcomes between the 2004 and 2013 academic years
      were known. METHODS: Academic outcomes were obtained from Tsukuba University's
      grade management system by permission of the authority. The students were divided
      into either a graduate or dropout group depending on their academic outcomes. The
      medical records for both groups were retrospectively investigated, and factors
      that were predicted to affect academic outcomes were assessed using statistical
      methods. RESULTS: The dropout group was younger in grade and had a greater
      severity of illness at initial consultation. Moreover, this group had a greater
      number of consultation visits, showed less cooperation with the instructor in
      charge, had a significantly longer duration of social with drawal and temporary
      leave of absence from school, and had a significantly greater number of students
      with grade retention. When a time factor was incorporated in the analysis, the
      presence of grade retention/temporary leave of absence from school and social
      withdrawal was significantly correlated with dropping out of school. CONCLUSION:
      It was revealed that not only the mental disorder itself, but also psychosocial
      severity and the maladjusted state that occur secondary to such mental disorder
      influence academic outcomes. These results indicated that in order to improve
      academic outcomes, it is necessary not only to appropriately treat the disorder,
      but to also provide university community support for social maladjusted states of
      the students in psychiatric treatments, such as social withdrawal, educational
      support for daily living, individual support for daily living, and academic
      support, through cooperation with the educational organization.

PMID- 27044139
TI  - [Why Do Psychiatrists Face Difficulties when Treating Dying Patients and Their
      Family Members?].
AB  - In recent years, psychiatrists in Japan have increasingly participated in
      palliative care teams. In this study, reasons why psychiatrists face difficulties
      when treating dying patients and their family members are discussed and some
      solutions are suggested. With respect to diagnosis, psychiatrists often hesitate
      to follow a normal psychological process in an effort to adhere to their
      specialty and do not consider subjective components in a patient's statement in
      the objective methodology of psychiatric diagnosis. In addition, many
      psychiatrists are unfamiliar with denial in the terminal phase or the desire for
      hastened death and are puzzled by how the psychic phenomena of dying patients are
      indistinguishable from physical symptoms. Family members of dying patients may
      hesitate to seek psychological treatment because they feel guilty about receiving
      such care. Moreover, recent changes in the diagnostic criteria of depression due
      to grief may be confusing to psychiatrists. From a therapeutic perspective,
      difficulties in diagnoses directly lead to therapeutic predicaments, and
      depression in the terminal phase is difficult to treat because antidepressant
      medications are not effective. To overcome such difficulties, I suggest that
      psychiatrists should also carefully consider patients' physical symptoms,
      reinforce categorical diagnoses with a subjective understanding, and deepen their
      understanding of spiritual pains.

PMID- 27044140
TI  - [Sometimes We Should Maintain a Mental Distance from a Patient--Relevance to
      Caring for Cancer Patients in Denial].
AB  - In Japan, cancer has been the leading cause of death since 1981 and is the most
      common and representative life-threatening disease. Cancer treatment has markedly
      progressed, and so the development of cancer is now not necessarily a death
      sentence. Nevertheless, approximately half of cancer patients actually die as a
      result of the disease even today. Cancer causes marked suffering of patients.
      Patients with advanced and/or terminal cancer suffer from various physical
      symptoms and are forced to face a continuous decline in their physical function,
      and previous studies reported that psychological distress is frequently observed
      in cancer patients, especially in advanced and/or terminally ill patients.
      Several types of psychological defense mechanism, especially denial, are
      frequently observed in these patients. There are multiple levels of denial For
      example, a patient with true denial denies the presence of cancer itself,
      although true denial is quite rare. A patient with moderate denial is likely to
      deny an association between distressing symptoms and disease, while one with mild
      denial denies the life-threatening nature of disease. Denial is a psychological
      defense mechanism that often helps advanced cancer patients to manage their
      anxiety and depression. It allows such patients to continue living while facing
      the painfulness of their situation. In this situation, it is important for
      therapists to note the patient's denial. Simply being aware of the denial can, in
      itself, be supportive for the patient. However, when denial does not work
      adaptively, such as it prohibiting adherence to necessary treatment and not being
      useful for ameliorating psychological distress and improving the quality of life,
      medical staff may consider confronting a patient with the reality of the
      situation carefully. This paper discusses the relevance of acknowledging denial
      and caring for patients with denial from the point of view of psycho-oncology.

PMID- 27044141
TI  - [Psychotherapy for Advanced Cancer Patients--The Importance of Support].
AB  - For patients with advanced cancer and their families, it is a challenge to adapt
      to their difficult situation. They have the potential power to do so, and medical
      staff can keep on supporting them to promote the process. Medical staff should
      not be afraid to relate to patients, and should adopt a flexible approach in
      parallel with patients' needs.

PMID- 27044142
TI  - [Bereavement Care in Cancer].
AB  - Bereavement may become the most severe stressor in the lives of bereaved
      families, and it has a variety of influences on their psychological and physical
      aspects. Physical effects include worsening of physical conditions and an
      increase in the mortality, and psychological ones include increases in the
      suicide rate and morbidity of depression. Bereavement also has a social
      influence, such as causing changes in relationships. Therefore, it is necessary
      to provide bereaved families requiring support with appropriate intervention.
      Since bereaved families experience various types of distress, assessment of grief
      related problems alone is inadequate. It is essential to assess the
      psychological, physical, social, and other aspects of bereaved families.
      Intervention can be expressed using the concept of postvention. There are various
      types of intervention : from care provided by non-specialists to psychiatric
      treatment provided by mental care specialists. Although bereavement is the
      strongest risk factor for depression, depressive symptoms following bereavement
      are often overlooked. Therefore, it is necessary to pay attention to such
      depression. Support is provided by not only health care professionals but also
      the general public in society, and it is essential to obtain knowledge of
      bereavement care in society. It should be noted that support not based on
      established knowledge may have an adverse effect on bereaved families (unhelpful
      support).

PMID- 27044143
TI  - [Basics of Pharmacotherapy for the Benefits of Patients].
AB  - The essence of drug therapy is to avoid the unnecessary use of drugs. We must
      initially consider whether or not to use a drug. For a depressive state, drugs
      are not necessary for an understandable psychological reaction, and should be
      carefully prescribed for mild depression with minor impairment in social and
      occupational functioning. Antidepressants do not have non-specific mood
      improvement effects. They exert effects by correcting the neurochemical imbalance
      related to the pathological depression. When we use pharmacotherapy, monotherapy
      is the basis. Monotherapy allows us to estimate the effects and side-effects
      properly, and to check the results with clinical evidence. Although the benefits
      of drug therapy are certain, we must remember that the risks cannot be reduced to
      zero even with efforts to minimize them.

PMID- 27044144
TI  - Awareness and implementation of the regional animal welfare strategy for the
      Americas: a questionnaire.
AB  - The World Organisation for Animal Health (OIE) is the global standard-setting
      organisation for animal health and these standards are references for the World
      Trade Organization legal framework. In 2002, noting the relationship between
      animal health and welfare, the OIE accepted the mandate to develop animal welfare
      standards. These standards were subsequently adopted by Member Countries and have
      been included in the TerrestrialAnimal Health Code and the Aquatic Animal Health
      Code. The implementation of the OIE standards by Member Countries is continually
      promoted. National OIE Delegates are encouraged to nominate National Focal Points
      for key topics, including animal welfare. In 2012, the OIE Regional Commission of
      the Americas adopted a Regional Animal Welfare Strategy (Regional Strategy) to
      promote a coordinated approach to the implementation of the OIE animal welfare
      standards by the 29 Member Countries in the region. In February 2015, the OIE
      Regional Representation for the Americas distributed a questionnaire to determine
      the level of awareness and implementation of the Regional Strategy. This paper
      presents the results of the questionnaire. With a few exceptions, veterinary
      officials and stakeholders are only just becoming aware of the strategy and
      implementation is at an early stage. To promote the implementation of the
      Regional Strategy, it will be.necessary to continue building the capacity of the
      national Veterinary Services, strengthening public-private partnerships,
      modernising legislation and promoting veterinary involvement in animal welfare.
      Through the implementation of the Regional Strategy, the OIE will provide support
      to countries in establishing animal welfare standards, in line with government
      priorities and consumer concerns.

PMID- 27044145
TI  - Scope for animal welfare education in open and distance learning: findings from a
      needs assessment study in India.
AB  - The objectives of this study were twofold: to assess the demand for animal
      welfare education by open and distance learning (ODL) and to identify content to
      be covered in an ODL animal welfare programme. Through email, personal interviews
      and online surveys, data were collected from 161 respondents. The key survey
      questions were on: the need and reasons for providing animal welfare education
      through ODL; entry-level qualifications; job/career prospects; duration of the
      programme, and suggestions on course content. The majority of respondents felt
      that there was a need for a one-year ODL academic programme on animal welfare. In
      the light of the findings of this study and related discussions, the authors
      recommend that online and ODL programmes in animal welfare be developed to meet
      the continuing educational needs of veterinary students, working veterinarians,
      para-veterinarians and other stakeholders closely related to animal welfare.

PMID- 27044146
TI  - Mental and physical distress of field veterinarians during and soon after the
      2010 foot and mouth disease outbreak in Miyazaki, Japan.
AB  - An outbreak of foot and mouth disease occurred in Miyazaki, Japan, in April 2010,
      and nearly 290,000 animals were culled to control the disease. This study was
      conducted to demonstrate the causes and intensity of mental distress felt by the
      field veterinarians participating in the control programme. A focus group
      discussion was conducted with ten veterinarians to understand their distress
      during the outbreak, and a questionnaire to quantify the degree of distress
      experienced each week was administered to 16 veterinarians. A detailed
      questionnaire was separately administered to 70 veterinarians six months after
      the outbreak was controlled, to assess mental distress status and to identify the
      risk factors for serious mental illness (SMI) using the six-item Kessler scale
      (K6). Overall, mental distress (mean 3.1) was significantly greater than physical
      distress (mean 1.9, p < 0.001). The risk factors for mental distress were
      categorised into three groups: culling, communication with farmers, and gender;
      each category was qualitatively described. Only two respondents (2.9%) had high
      K6 scores suggesting SMI. In the final generalised linear models with quasi
      Poisson errors, the riskfactorsfor SMI that remained were: disinfecting vehicles
      (p = 0.01), distress (p <0.001), and increased alcohol consumption (p = 0.057),
      and a protective factor: participation in culling (p = 0.07), which suggested
      healthy worker bias. Sensitive individuals had been allocated to non-culling
      activities during disease control. In conclusion, human resource management was
      adequate during the outbreak from a public-health perspective. However,
      monitoring delayed symptoms of post-traumatic stress disorder is recommended.

PMID- 27044147
TI  - Veterinary public health in India: current status and future needs.
AB  - Veterinary public health (VPH) assumes huge significance in developing countries
      such as India. However, the implementation of VPH services throughout the country
      is still in its infancy. From 1970 onwards, many institutes, national and
      international organisations, professional societies, policies and personalities
      have contributed towards the development of VPH in India. Nevertheless, there is
      an urgent need to develop VPH still further as there are many issues, such as
      high population density, the re-emergence of zoonotic pathogens, environmental
      pollution and antimicrobial resistance, that require attention. The time has
      surely come to involve all stakeholders, ranging from primary producers (e.g.,
      farmers) to policy-makers, so as to garner support for the holistic
      implementation of VPH services in India. To improve VPH activities and services,
      science-based policies enforced through stringent regulation are required to
      improve human, animal and environmental health. The emergence of the 'One Health'
      concept has ushered in new hopes for the resurrection of VPH in India. Applying
      tools such as the World Organisation for Animal Health (OlE) Day One Competencies
      and the OlE Tool for the Evaluation of Performance of Veterinary Services (PVS
      Tool) is essential to improve the quality of national Veterinary Services and to
      identify gaps and weaknesses in service provision, which can be remedied to
      comply with the OlE international standards. VPH initiatives started modestly but
      they continue to grow. The present review is focused on the current status and
      future needs of VPH in India.

PMID- 27044148
TI  - Emergency vaccination use in a modelled foot and mouth disease outbreak in
      Minnesota.
AB  - Epidemiological modelling is an important approach used by the Veterinary
      Services of the United States Department of Agriculture Animal and Plant Health
      Inspection Service to evaluate the potential effectiveness of different
      strategies for handling foot and mouth disease (FMD). Identifying the potential
      spread of FMD by modelling an outbreak, and then considering the impacts of FMD
      vaccination, is important in helping to inform decision-makers about the
      potential outcomes of vaccination programmes. The objective of this study was to
      evaluate emergency vaccination control strategies used in a simulated FMD
      outbreak in Minnesota. The North American Animal Disease Spread Model (NAADSM,
      Version 3.2.18) was used to simulate the outbreak. Large-scale (1,500 herds per
      day) emergency vaccination reduced the size of the modelled outbreak in both
      swine and dairy production types, but the effect was larger when the outbreak
      began in a dairy herd. Large-scale vaccination also overcame limitations caused
      by delays in vaccine delivery. Thus, even if vaccination did not begin until 21
      days into the outbreak, large-scale vaccination still reduced the size and
      duration of the outbreak. The quantity of vaccine used was markedly larger when
      large-scale vaccination was used, compared with small-scale (50 herds per day)
      vaccine administration. In addition, the number of animals and herds vaccinated
      in an outbreak originating in a herd of swine was substantially lower than in an
      outbreak beginning in a herd of dairy cattle.

PMID- 27044149
TI  - Importance of foot and mouth disease vaccine purity in interpreting serological
      surveys.
AB  - The aim of this study was to determine whether the degree of purity achieved in
      conventional vaccines against the foot and mouth disease virus in Argentina
      interferes with the interpretation of seroepidemiological surveys for confirming
      the absence of viral activity, which are performed to support the recognition of
      free zones practising vaccination. The evaluation of 168 vaccine series due to be
      marketed in Argentina (2006-2012) and subjected to official control testing in
      cattle, as well as repeated vaccination of cattle and other species using
      vaccines with high antigen concentrations, demonstrated that they did not induce
      antibodies to non-structural proteins (NSPs). The results show clearly that
      vaccines with satisfactory potency do not induce a response to NSPs, even by
      forcing the immune response through more concentrated doses with multiple
      valences and revaccination protocols at shorter irtervals than in vaccination
      campaigns. These results confirm that the vaccines used in routine vaccination
      programmes have a degree of antigen purification consistent with the needs
      observed on the basis of sampling for serological surveillance. Moreover,
      serological surveys conducted in 2006-2011 by Argentina's official Veterinary
      Services--the National Health and Agrifood Quality Service (SENASA)--on more than
      23,000 sera per year from cattle included in the vaccination programme, in order
      to confirm the absence of virus circulation, revealed an average 0.05% of
      reactive results, consistent with the specificity of the tests. In conclusion,
      the vaccines produced by conventional methods and with proven potencythat are
      available in Argentina are sufficiently purified to ensure thatthey do not
      interfere with the interpretation of sampling for serological surveillance
      performed to support the recognition of FMD-free zones practising vaccination.

PMID- 27044150
TI  - Improving the delivery of veterinary services in India.
AB  - In pursuit of effective veterinary service delivery, the objectives of this study
      were threefold: (i) reduce the shortage of technical personnel in veterinary
      universities (VUs) and animal husbandry departments (AHDs), (ii) identify
      collaborative areas between VUs and AHDs, and (iii) build the capacity of the
      veterinary and animal husbandry sector. Primary data were collected from all the
      16 veterinary colleges and AHDs in five south Indian states on: (i) student
      intake and the out-turn of veterinary graduates, (ii) technical personnel-
      existing and required at various levels, (iii) specific areas of collaboration
      where VUs and AHDs need each other and can extend support to each other, and (iv)
      areas in which university faculty and field veterinarians would benefit from
      further training. Two focus group discussions were held with top administrators
      of VUs and AHDs to collect qualitative data. The results revealed that there are
      not enough veterinary graduates to meet the needs of the system and that there is
      a shortage of faculty, field veterinarians and para-veterinarians. Both focus
      groups identified areas for collaboration and capacity building to improve
      veterinary service delivery. The results conclusively demonstrated that India's
      veterinary service delivery is constrained, not due to a lack of organisations or
      programmes, but due to the inability of the organisations to collaborate with
      each other. To improve the effectiveness of veterinary service delivery it will
      be necessary to: admit more graduate students, support the establishment of new
      colleges; recruit faculty, field veterinarians and para-veterinarians; remandate
      the Directorates of Extension at VUs to develop linkages with AHDs; allocate
      funds ('special central grants') for infrastructure development to all AHDs and
      veterinary colleges; establish one model veterinary college that follows
      international standards on veterinary education and create four regional academic
      staff training colleges exclusively for the purpose of developing the capacity of
      the veterinary and animal husbandry sector. Action plans to implement these
      recommendations are also suggested.

PMID- 27044151
TI  - An appraisal of the Maltese national livestock database with regard to bovines.
AB  - The creation of a centralised national livestock database for the islands of
      Malta and Gozo is of crucial importance for the identification and traceability
      of bovines. It is also important for compliance with the legal obligations that
      followed Malta's accession to the European Union in May 2004. This paper
      describes how the processes of identification, registration and traceability of
      bovines have changed since Malta's accession. The validation and integration of
      data originating from different departmental sections (such as the identification
      and registration section), the slaughterhouse and the National Veterinary
      Laboratory, ensures that any discrepancies are highlighted and can be
      investigated. Events recorded in the database enable the compliance and
      eligibility of bovine producers to be cross-checked when applications for
      European Union benefits are made. The main drawbacks and weak points of the
      system include financial costs for the government department, potentially late
      notification of the births and deaths of newborn calves, and insufficient uptake
      among bovine producers of the latest technology for notification of events such
      as births, deaths and movement of bovines.

PMID- 27044152
TI  - The spread of non-OIE-listed avian diseases through international trade of
      chicken meat: an assessment of the risks to New Zealand.
AB  - Twelve avian diseases are listed by the World Organisation for Animal Health
      (OIE), although more than 100 infectious diseases have been described in
      commercial poultry. This article summarises a recent assessment of the
      biosecurity risks posed by non-listed avian diseases associated with imports of
      chilled or frozen chicken meat and meat products into New Zealand. Following the
      guidelines described in Chapter 2.1 of the OIE Terrestrial Animal Health Code,
      avian adenovirus splenomegaly virus, avian paramyxovirus-2 (APMV-2), Bordetella
      avium, Mycoplasma spp., Ureaplasma spp., Ornithobacterium rhinotracheale,
      Riemerella anatipestifer, and Salmonella arizonae have been identified as
      hazards. However, of all the non-listed avian diseases discussed here, only APMV
      2 and S. arizonae are assessed as being risks associated with the commercial
      import of chicken meat into New Zealand. Specific control measures may have to be
      implemented to mitigate such risks. This conclusion is likely to reflect both the
      high-health status of New Zealand poultry and the threat posed by these
      infectious agents to New Zealand's unique population of native psittacine
      species.

PMID- 27044153
TI  - Cost-benefit analysis of avian influenza control in Nepal.
AB  - Numerous outbreaks of highly pathogenic avian influenza A strain H5N1 have
      occurred in Nepal since 2009 despite implementation of a national programme to
      control the disease through surveillance and culling of infected poultry flocks.
      The objective of the study was to use cost-benefit analysis to compare the
      current control programme (CCP) with the possible alternatives of: i) no
      intervention (i.e., absence of control measures [ACM]) and ii) vaccinating 60% of
      the national poultry flock twice a year. In terms of the benefit-cost ratio,
      findings indicate a return of US $1.94 for every dollar spent in the CCP compared
      with ACM. The net present value of the CCP versus ACM, i.e., the amount of money
      saved by implementing the CCP rather than ACM, is US $861,507 (the benefits of
      CCP [prevented losses which would have occurred under ACM] minus the cost of
      CCP). The vaccination programme yields a return of US $2.32 for every dollar
      spent when compared with the CCR The net present value of vaccination versus the
      CCP is approximately US $12 million. Sensitivity analysis indicated thatthe
      findings were robust to different rates of discounting, whereas results were
      sensitive to the assumed market loss and the number of birds affected in the
      outbreaks under the ACM and vaccination options. Overall, the findings of the
      study indicate that the CCP is economically superior to ACM, but that vaccination
      could give greater economic returns and may be a better control strategy. Future
      research should be directed towards evaluating the financial feasibility and
      social acceptability of the CCP and of vaccination, with an emphasis on
      evaluating market reaction to the presence of H5N1 infection in the country.

PMID- 27044154
TI  - Emergency surveillance for novel influenza A(H7N9) virus in domestic poultry,
      feral pigeons and other wild birds in Bhutan.
AB  - Following the March 2013 outbreak of novel avian influenza A(H7N9) virus in
      humans and the subsequent isolation of the virus from chickens, ducks and pigeons
      in the People's Republic of China, concerns were raised that the H7N9 virus would
      spread beyond China through the poultry value chain linking to a number of
      bordering countries. For this reason, a rapid emergency surveillance exercise
      took place in Bhutan between May and July 2013 with the objective of determining
      whether influenza A(H7N9) virus was silently circulating in domestic
      poultryandwild birds in Bhutan.Atotal of 1716 oropharyngeal,tracheal and cloacal
      swabs together with faecal droppings were collected from poultry, wild birds and
      feral pigeons throughout the country; these samples included 150 that had been
      previously collected for surveillance of influenza A(H5N1) virus. Overall, 733 of
      the samples were tested. A QIAamp Viral RNA Mini K it was used to extract viral
      RNA from a mix of oropharyngeal, tracheal and cloacal swabs and faecal droppings.
      The matrix gene of avian influenza type A virus was detected using a specific
      real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR)
      assay, and positive samples were further tested in RT-PCR for simultaneous
      detection of the H7 and N9 genes. Among the 733 samples tested, 46 (26
      prospective, 20 retrospective) were confirmed positive for influenza A, a
      prevalence of 6.3% (95% CI: 4.6 to 8.3). The influenza A-positive samples were
      from areas in the south of Bhutan that had experienced previous outbreaks of
      highly pathogenic influenza A(H5N1). None of the samples tested positive for H7N9
      strains, providing evidence that influenza A(H7N9) virus was not present in the
      sampled population. A risk-based approach for surveillance of influenza A(H7N9)
      and H5N1 is recommended in Bhutan, based on the epidemiology of the disease in
      China and other countries in South and Southeast Asia.

PMID- 27044155
TI  - 'High-health, high-performance' horses: risk mitigation strategies for OIE-listed
      diseases.
AB  - The 'high-health, high-performance' (HHP) horse concept has been developed by the
      World Organisation for Animal Health (OIE) together with the F6ddration Equestre
      Internationale and the International Federation of Horseracing Authorities. This
      concept is outlined in the OIE Terrestrial Animal Health Code (Chapter 4.16). It
      aims to address impediments to the international movement of competition horses
      through a harmonised, practically feasible, globally applicable framework based
      on simplified certification requirements for the temporary importation of HHP
      horses and for their return to their country of usual residence. Based on the
      principle of compartmentalisation, the high health status of these horses would
      be established by the application, at all times, of stringent health management
      practices and biosecurity measures to create and maintain a functional separation
      between horses within the defined compartment and all other equids. These
      provisions are intended to mitigate the risk of disease spread for most OIE
      listed diseases. For six OIE-listed diseases (African horse sickness, equine
      influenza, equine infectious anaemia, equine piroplasmosis, glanders and
      Venezuelan equine encephalomyelitis), the OIE recommends disease-specific
      mitigation measures, which have been included in a model HHP Veterinary
      Certificate, to provide additional guarantees to mitigate the risk of disease
      spread. This article presents the HH P disease risk mitigation strategy. It
      demonstrates how continuous observance of the HHP biosecurity measures and health
      management practices provides a scientific rationale for limiting the list of
      diseases for which HHP horses should be screened with respect to their temporary
      importation for competition purposes.

PMID- 27044156
TI  - Identification of Dermatophilus congolensis from lower leg dermatitis of cattle
      in Kerala, India.
AB  - This study was conducted to identify the aetiological agents associated with a
      particular type of lower leg dermatitis, locally called pododermatitis, among
      dairy cattle in Kerala. Skin scabs and scrapings were collected aseptically from
      82 naturally occurring cases of lower leg dermatitis in cattle and were subjected
      to direct microscopical examination and bacterial and fungal culture.
      Microscopical examination of the skin scrapings with 10% potassium hydroxide
      revealed fungal spores in hair shafts from only two samples and did not reveal
      the presence of mites or other parasites. Fungal culture yielded dermatophytes
      from only five samples; these were identified as Trichophyton mentagrophytes in
      two cases, T verrucosum in one case, Epidermophyton floccosum in one case and
      Microsporum nanum in one case. Microscopical examination of Giemsa- and Gram
      stained smears of the scab material from the lesions from 72 cases revealed
      characteristic Gram-positive septate branching filaments with multiple rows of
      spherical to ovoid cocci, with a typical 'tram-track' appearance suggestive of
      Dermatophilus congolensis. Culture of the scab materials on sheep blood agar in
      the presence of 10% carbon dioxide yielded typical beta haemolytic colonies of D.
      congolensis from 75 samples. The isolates were further confirmed by the
      macroscopic and microscopic morphology of the colonies, and biochemical test
      results. This study confirmed the presence of dermatophilosis caused by D.
      congolensis in cattle in Kerala.

PMID- 27044157
TI  - Infectious lameness among migratory sheep and goats in north-west India, with
      particular focus on anaerobes.
AB  - Various bacterial species, particularly Dichelobacter nodosus, Fusobacterium
      necrophorum, Trueperella pyogenes (previously Arcanobacterium pyogenes) and
      Treponema spp., have been implicated in infectious conditions manifesting in
      lameness in sheep and goat populations. The current study reports the causes of
      infectious lameness in the north-western Himalayan region, particularly Himachal
      Pradesh (HP), where no such study has been conducted in the past. Among a total
      surveyed population of 27,586 animals, comprised of 15,006 sheep and 12,580
      goats, 216 samples were collected from foot lesions. A total of 6.48% (14/216)
      samples were positive for D. nodosus, 20.83% (45/216) for F. necrophorum and
      20.37% (44/216) for T pyogenes. In three instances, all of the three
      aforementioned bacteria were present in a single foot lesion. Most of the
      positive samples were from areas in the state of HP adjoining the state of Jammu
      and Kashmir (J&K), where footrot is endemic. The confirmation of footrot in HP
      and the fact that F. necrophorum and T pyogenes were detected from cases of
      foot/hoof infection in high numbers emphasises thatthese organisms play an
      important role in inducing morbidity in migratory sheep and goats. The present
      investigation also confirms the detection of D. nodosus from cases of footrot for
      the first time from HP. With new reports identifying F. necrophorum as a pathogen
      with a potential role in aggravating infection caused by footrot, the development
      of a combined vaccine to prevent lameness in sheep and goats in the north-western
      Himalayan region has been suggested.

PMID- 27044158
TI  - Development of 316v antibody enzyme-linked immunosorbent assay for detection of
      paratuberculosis in sheep.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed and optimised using a
      Mycobacterium avium subspecies paratuberculosis (MAP) antigen prepared from a C
      strain (316v) passed through a French press. The optimised assay was evaluated
      with a panel of sera from MAP infected (n = 66) and uninfected (n = 1,092) sheep.
      Animals in the MAP infected category were positive on either tissue culture or
      histopathology but were of unknown serum antibody status. The diagnostic
      performance and cost of the assay were compared with those of a commercial ELISA
      (IDEXX). At 99.8% diagnostic specificity the assay showed a diagnostic
      sensitivity of 23% (95% CI: 15.1-35.8) compared with 36.4% (95% CI: 25.8-48.4)
      for the commercial ELISA (McNemar's test: chi-square 5.82, p < 0.05). The
      sensitivities were 5.9% (95% CI: 1-26.9), 27.9% (95% CI: 14.7-45.7) and 35% (95%
      CI: 18.1-56.7), for low grade, paucibacillary and multibacillary lesion grades,
      respectively. The cost of the commercial assay kit was 2.7 to 5.2 times greater
      than that of the 316v ELISA for an equivalent number of tests, the multiple
      depending on the number of plates processed per run. For flock-level
      surveillance, to account for the lower sensitivity of the 316v ELISA compared
      with the commercial ELISA, sample sizes would be increased but the test cost
      would still be lower. The 316v assay will be useful for diagnosis of Johne's
      disease in sheep flocks, particularly in developing countries where labour costs
      are low relative to the cost of consumables.

PMID- 27044159
TI  - Epidemiological survey of brucellosis in sheep and goats in selected pastoral and
      agro-pastoral lowlands of Ethiopia.
AB  - An epidemiological survey was conducted in pastoral regions of Ethiopia to
      investigate the distribution of brucellosis in sheep and goats. Between November
      2004 and December 2007, a total of 6,201 serum samples were collected from 67
      randomly selected peasant associations, 25 districts and eight pastoral zones of
      Ethiopia. The Rose Bengal plate test (RBPT) and complement fixation test were
      used in series. Samples for bacteriology were collected from three export
      abattoirs, where 285 goats were randomly selected and tested by RBPTthree days
      before slaughter. Tissue samples were collected from 14 strongly positive goats
      and cultured in dextrose agar and Brucella agar base. To confirm and subtype the
      isolates, staining, biochemical tests and polymerase chain reaction were used.
      The overall standardised seroprevalence of brucellosis was 1.9%, ranging from
      0.07% in Jijiga zone to 3.3% in Borena zone. There was statistically significant
      variation among the studied regions, zones, districts and peasant associations (p
      < 0.05). Male goats and sheep were twice as likely to test positive as females
      (relative risk [RRJ: 2.04; 95% confidence interval [CI]:1.7-3.4; x2 = 21.05, p <
      0.05). Adults (older than 1.5 years) were three times more likely to test
      positive than younger animals (RR: 2.76; 95% CI: 1.14-6.73; chi2 = 5.18, p <
      0.05). Goats were around four times more likely to be infected than sheep (RR:
      3.8; 95% CI: 2.4-6.1; chi2 = 36.99, p < 0.05). Brucella melitensis was isolated
      from 2 of the 14 samples analysed. The widespread distribution of brucellosis in
      goats and sheep in these areas justifies the use of control measures to minimise
      the economic losses and public health hazards.

PMID- 27044160
TI  - Epidemic simulation of a foot and mouth disease outbreak in Minnesota.
AB  - Foot and mouth disease (FMD) is a primary transboundary livestock disease of
      international concern. Outbreaks of the disease have recently occurred in several
      countries that were previously FMD-free. For countries with limited direct
      experience of this disease, modelling is a useful tool for the study of a
      potential outbreak. The objectives of this study were to determine specific FMD
      risk parameters for Minnesota and the United States (USA) and to use these
      parameters to create a baseline FMD outbreak model for Minnesota. Of specific
      interest was to assess whether the type of herd in which the outbreak began (a
      dairy herd or a large-scale swine herd) influenced the basic model outcomes of
      outbreak size and duration, and to examine the effects of depopulation and
      movement controls. The mean values for disease duration, outbreak duration and
      number of farms and animals infected were larger in the scenario with a dairy
      index herd. The results of these two outbreak models demonstrated the entire
      spectrum of FMD outbreak types; that is, from limited, focal outbreaks to
      widespread, uncontrolled outbreaks. The findings from this study provide details
      of a baseline model that emergency preparedness planners can use to evaluate
      response strategies for a potential incursion of FMD into the USA. These findings
      are also of value for all countries as veterinary authorities develop or adjust
      their FMD emergency response plans.

PMID- 27044161
TI  - Caprine arthritis encephalitis virus: prevalence and risk factors in Lebanon.
AB  - An epidemiological survey, accompanied by a serological analysis,was conducted on
      samples taken from Lebanese goat herds in order to determine the prevalence of
      infection with the caprine arthritis encephalitis virus (CAEV) in Lebanon. The
      results of the survey provided information on various livestock production,
      animal health and herd management factors. Serum samplesfrom 952 goats, including
      the local breeds (Baladi and Damascene) and imported breeds (Alpine and Saneen),
      were taken from 60 farms distributed throughout Lebanon and tested for the
      presence of anti-CAEV antibodies. The data obtained were analysed using a
      statistical model to assess CAEV infection risk factors in Lebanon. In total, 125
      samples proved to be positive, representing a prevalence in selected individuals
      of 13.1% and in selected herds of 51.7%. The Bekaa region had the highest number
      of herds with seropositive goats (90% of herds); the level was lower in Mount
      Lebanon, the North and the South (54%, 34% and 33%, respectively). The prevalence
      in relation to the livestock production system was 70% in herds in intensive
      systems, 54% in semi-intensive systems and 45% in extensive systems. The
      indigenous breeds were more resistant and tolerant of CAEV than the imported
      breeds. This study confirms the presence of CAEV in Lebanese goat herds and
      identifies the different livestock production practices likely to favour the
      rapid spread of the virus.

PMID- 27044162
TI  - Controlling emerging infectious diseases in salmon aquaculture.
AB  - In this paper, the authors review the impacts of diseases facing salmon
      aquaculture, drawing lessons from terrestrial animal diseases. They discuss the
      implementation of current control strategies, taking into account transmission
      patterns (vertical versus horizontal), disease reservoirs, and interactions with
      wild fish. In addition, the decision-making context of aquatic disease control
      and the institutional organisation of control strategies are considered, with
      particular emphasis on the roles and responsibilities of regulatory authorities
      and the private sector. Case studies on the emergence and control of infectious
      salmon anaemia worldwide and pancreas disease in Norway are used to examine some
      of the controversies that may influence decision making and provide lessons for
      the future.

PMID- 27044163
TI  - Foot and mouth disease in selected districts of western Ethiopia: seroprevalence
      and associated risk factors.
AB  - A study was conducted in western Ethiopia--in two districts of Oromia state and
      four districts of Beneshangul Gumuz state--to determine the seroprevalence of
      foot and mouth disease and the associated risk factors, using multistage random
      sampling. A 3ABC blocking enzyme-linked immunosorbent assay was used to measure
      antibody against the non-structural protein of foot and mouth disease virusto
      differentiate between vaccinated and infected animals.Atotal of 1,144 sera from
      181 herds were collected and examined. The overall seroprevalence at animal level
      and herd level was 9% (95% Cl 7.2-10.6) and 38.1% (95% CI 29.1-47.1),
      respectively. Statistically significant differences (p < 0.05) were recorded
      among different species, with 13%, 5% and 3% seropositivity in cattle, sheep and
      goats, respectively. Statistically significant differences (p < 0.05) in herd
      seroprevalence were observed among districts, with 52%, 50%, 50%, 44%, 21% and
      11% in Gidami, Begi, Tongo, Bambasi, Mange and Asosa districts, respectively. In
      univariable and multivariable logistic regression, the variables that had a
      positive relationship with seroprevalence at herd level (p < 0.05) were herd
      size, contact of livestock with ungulate wildlife, and contact of animals with
      animals/herds of a different peasant association. Univariable and multivariable
      logistic regression analysis indicated that, at the animal level, age and species
      had a statistically significant association (p < 0.05) with seropositivity. In
      conclusion, herd size, contact of livestock with ungulate wildlife, contact
      between herds from different peasant associations, and the age and species of the
      animals were the main risk factors for virus circulation in the study area.

PMID- 27044164
TI  - Prevalence and molecular epidemiology of porcine cysticercosis in naturally
      infected pigs (Sus scrofa) in Punjab, India.
AB  - Porcine cysticercosis is a serious zoonosis in resource-poor countries. Despite
      the evidence showing that the disease is endemic in the Punjab region of India,
      molecular characterisation of Taenia solium cysticercosis from naturally infected
      pigs has not been carried out. The authors examined a total of 519 pigs
      slaughtered in small slaughter shops (shops that sell meat from animals that are
      slaughtered on the premises as the customer waits) in the urban slums of Punjab
      state in northern India. The expected polymerase chain reaction products with
      molecular sizes of 286 bp, 420 bp, 1150 bp and 333 bp corresponding to the
      targeted large subunit ribosomal RNA (rRNA), cytochrome oxidase 1, internal
      transcribed spacer 1, and diagnostic antigen Ts14 genes, respectively, were
      amplified from the cysts collected from all 22 infected carcasses. The detection
      limits for the respective primers (except those targeting the Ts14 gene) were
      estimated. The analytical sensitivities of both the TBR and JB primers (targeting
      the rRNA and cytochrome oxidase genes, respectively) were found to be higher (10
      pg) than that of the internal transcribed spacer 1 gene (1 ng) primers. Ten
      representative samples from cytochrome oxidase 1 gene amplified products were
      sequenced in both directions for phylogenetic analysis. Sequencing demonstrated
      that all cysticerci were of the Asian genotype of T. solium and not of the
      African/Latin American genotype or T. asiatica. The results confirm the presence
      of T. solium porcine cysticercosis in Punjab state and there is therefore an
      urgent need for science-based policies for prevention and control of this serious
      zoonosis.

PMID- 27044165
TI  - Quantitative risk assessment of the likeihood of introducing porcine reproductive
      and respiratory syndrome virus into New Zealand through the importation of pig
      meat.
AB  - A quantitative model was developed to estimate the likelihood of an incursion of
      porcine reproductive and respiratory syndrome virus (PRRSV) into New Zealand
      through the importation of fresh consumer-ready cuts of pig meat. A sensitivity
      analysis of all the inputs used in this model illustrated the importance of
      correctly modelling the available 'dose-response' data, and a mechanistic Beta
      Poisson model was shown to be the most appropriate method for this in the
      authors' assessment. The output of this model predicts an average of
      approximately 1,200 years between PRRSV introductions resulting in primary
      infections in New Zealand. Given the uncertainties in the model, there is 95%
      confidence that this time period ranges from 52 to 6,200 years. The values chosen
      in this model are considered to provide a conservative estimate of the likelihood
      of introducing PRRSV into New Zealand via the importation of fresh pork.

PMID- 27044166
TI  - Implementation of an HACCP model in foot and mouth disease control programmes.
AB  - The organisation and structure of the official Veterinary Services (OVS) are
      designed to meet a specific aim--the health certification of animal health,
      welfare and food safety in the production and processing stage. Disease
      prevention and control calls for programmes and projects that, depending on the
      characteristics of each disease, may involve any branch of the OVS, from the
      laboratory to field activities. For the purpose of this work, the model used is
      that of a country that is 'free from foot and mouth disease with vaccination' in
      accordance with the conditions stipulated in Chapter 8.8. of the World
      Organisation for Animal Health Terrestrial Animal Health Code. These conditions
      state that, to maintain this health status, a programme of monitoring and
      continuous control of the relevant variables must be implemented. This is
      achieved by applying good practice and identifying the critical control points in
      all processes, using a checklist that simplifies the task. The system that is
      developed can also serve as a guide for internal or external programme audits.

PMID- 27044167
TI  - Assessing the economic burden of avian infectious bronchitis on poultry farms in
      Brazil.
AB  - Avian infectious bronchitis (IB), caused by avian infectious bronchitis virus
      (IBV), is a worldwide endemic disease of chickens that affects all branches of
      the poultry industry. Multiple geno/serotypes occur, and lowvaccine cross
      protection results from the highly divergent IBV types. In view of the lack of
      consistent data on the economic losses caused by IB and the poor protection
      resulting from the use of the Massachusetts type as a live vaccine in Brazil,
      this survey aimed to estimate the losses per 1000 birds in broiler and breeder
      flocks positive for IBV. Thirty-two different IBV genetic types were found. In
      breeders, the total loss per 1,000 birds was US $3567.4 and US $4210.8 at 25-26
      and 42 weeks old, respectively, whereas in broilers (48 days old), the estimated
      loss was US $266.3 per 1,000 birds. Taken together, the results show a
      significant and measurable economic impact on the broiler and breeder industries,
      with an age-dependent increasing trend and an association with multiple genetic
      types of the virus.

PMID- 27044168
TI  - The genetic population structure of Mycobacterium bovis strains isolated from
      cattle slaughtered at the Yaounde and Douala abattoirs in Cameroon.
AB  - Bovine tuberculosis is still prevalent and under-evaluated in cattle destined for
      human consumption in Cameroon. Potential reservoirs of the disease include
      livestock imported from countries endemic for bovine tuberculosis, such as
      Nigeria and Chad, and potential residual reservoirs in local livestock and
      wildlife. Few studies have been done in Cameroon to genotype the Mycobacterium
      tuberculosis complex (MTC) strains responsible for bovine tuberculosis. The aim
      of this work is to describe the population structure of MTC strains isolated from
      cattle, using spoligotyping as the genotyping method. Out of 218 organs or
      tissues from cattle with suspected tuberculosis lesions, 90 MTC strains were
      isolated and underwent molecular typing; among them, 86 strains were identified
      as M. bovis and four strains as M. tuberculosis. The M. tuberculosis strains
      belonged to rare M. tuberculosis lineages of the U family; among the M. bovis
      strains SB0944 was the most prevalent. Eight new spoligotype patterns were
      identified, representing 33% (30/90) of all isolates. Among these new
      spoligotypes, SB1955 was dominant. The spoligotype patterns of 85 M. bovis
      strains lacked spacer 30, a common characteristic of the M. bovis lineage African
      1, described earlier in Cameroon, Chad, Mali and Nigeria. This study shows
      ongoing tuberculosis transmission involving M. bovis lineages not previously
      described as the leading cause of disease. It also shows a possible reverse
      zoonosis from humans to cattle.

PMID- 27044169
TI  - High-quality of Care throughout Europe--But Do We Speak the Same Language?

PMID- 27044170
TI  - Tracing the Boundaries between Disability and Sickness in the European Union:
      Squaring the Circle?
AB  - In recent years the European Union (EU) has sought to develop a far-reaching
      policy regarding persons with disabilities. However, to date, EU non
      discrimination legislation does not provide any clear legal definition of what
      constitutes a disability. The Court of Justice of the European Union (CJEU) has
      attempted to fill this gap and, in several decisions, has elaborated on the
      concept of disability and its meaning under EU law. The CJEU, with reference to
      the application of the Employment Equality Directive, has explained the notion of
      disability mainly by comparing and contrasting it to the concept of sickness.
      Against this background, this article critically discusses recent case law and
      attempts to highlight that, even though the Court has firmly embraced the social
      model of disability envisaged by the UN Convention on the Rights of Persons with
      Disabilities, the boundaries between the concepts of sickness and disability
      remain blurred.

PMID- 27044171
TI  - Patient Mobility in Times of Austerity: A Legal and Policy Analysis of the Petru
      Case.
AB  - The case-law of the Court of Justice (ECJ) on patient mobility was recently
      challenged by a ruling that a patient could go to Germany for treatment when
      facilities in Romanian hospitals were inadequate. Given the reported impact of
      austerity measures in the field of health care this raises the question; what is
      the impact of the ECJ's ruling on how Member States can manage expenditure and
      limit outflows of patients and how should such measures be legally evaluated? The
      objective of this article is to analyse potential impact on health systems in the
      context of increasing pressure on public financing for health. While the ECJ
      mainly referred to the requirement of treatment in due time, we also analyse
      possible austerity reductions of the basket of care against the background of EU
      law (i.e., EGJ case-law, patient mobility directive, Charter of Fundamental
      rights and social security regulation).

PMID- 27044172
TI  - The Interfamilial Principle and the Harvest Festival.
AB  - It is widely accepted that younger children can act as saviour siblings by
      donating cord blood or bone marrow to their gravely-ill brothers or sisters.
      However, it is under dispute whether these procedures are in the best interests
      of the child. This article suggests that parents may be relying on a thinly
      veiled interfamilial approach, where the wider benefit to the whole family is
      used to justify the procedure to the Human Tissue Authority in the United
      Kingdom. This article suggests that the merging of familial interests to validate
      a non-therapeutic bone marrow harvest on a child forces altruism in a patient too
      young to understand, rendering the harvests unlawful under current law.

PMID- 27044173
TI  - European Court of Human Rights. ECHR 2016/1 Case of Nicklinson and Lamb v. the
      United Kingdom, 16 July 2015, no. 2478/15 and 1787/15 (Fourth Section).

PMID- 27044174
TI  - European Court of Human Right. ECHR 2016/2 Case of Akkoyunlu v. Turkey, 13
      October 2015, no. 7505/06 (Second Section).

PMID- 27044175
TI  - European Court of Human Rights. ECHR 2016/3 Case of Annen v. Germany, 26 November
      2015, no. 3690/10 (Fifth Section).

PMID- 27044176
TI  - European Court of Human Rights. ECHR 2016/4 Case of Lopes de Sousa Fernandes v.
      Portugal, 15 December 2015, no. 56080/13 (Fourth Section).

PMID- 27044177
TI  - European Court of Justice. ECJ 2016/1, Smaranda Bara and Others v. Presedintele
      Casei Nationale de Asigurari de Sanatate, Casa Nationala de Asigurari de
      Sanatate, Agentia Nationala de Administrare Fiscala (ANAF), 1 October 2015 (Case
      C-201/14).

PMID- 27044178
TI  - [New possibilities will open up in human gene therapy].
AB  - Gene therapy is divided into somatic and germ line therapy. The latter involves
      reproductive cells or their stem cells, and its results are heritable. The
      effects of somatic gene therapy are generally restricted to a single tissue of
      the patient in question. Until now, all gene therapies in the world have belonged
      to the regime of somatic therapy, germ line therapy having been a theoretical
      possibility only. Very recently, however, a method has been developed which is
      applicable to germ line therapy as well. In addition to technical challenges,
      severe ethical problems are associated with germ line therapy, demanding opinion
      statement.

PMID- 27044179
TI  - [Treatment of primary hypothyroidism in adult patients].
AB  - The diagnosis of hypothyroidism is based on the findings of an increased serum
      TSH (above the reference range) and decreased serum free T4 (below the reference
      range) concentration. Treatment of subclinical hypothyroidism is indicated if
      serum THS is above 10 mU/l. For less severe forms of subclinical hypothyroidism,
      the treatment should be individually tailored. The treatment of choice is
      synthetic human levothyroxine. The goals for treatment are amelioration of
      symptoms and normalization of TSH and free T4 concentrations.

PMID- 27044180
TI  - [Adverse effects of new immunologic drugs for melanoma and their management in
      adult patients].
AB  - Conventional anticancer drugs, cytotoxic agents, function by killing all rapidly
      dividing cells without distinguishing between cancer cells and normal cells of
      the body. Understanding of the regulatory mechanisms of the immune system has
      enabled the development of immunotherapeutic drugs and, through them, liberation
      of the immune response for the management of cancer. In Finland, interferons and
      antibody therapies represent the clinically applied immunotherapy of melanoma.
      While most antibody therapies are fairly harmless, the new drugs enhancing T cell
      defense are associated with a significant risk of autoimmune adverse effects.
      Immediate recognition and treatment of adverse effects are essential for the
      survival of the patients.

PMID- 27044181
TI  - [Polyvagal theory and emotional trauma].
AB  - According to the polyvagal theory, the autonomic nervous system can, in deviation
      from the conventional theory, be divided in three distinct parts that are in
      hierarchical relationship with each other. The most-primitive autonomic control
      results in depression of vital functions, the more evolved one in fighting or
      escape and the most evolved one in social involvement. Practical application of
      the polyvagal theory has resulted in positive results above all in the treatment
      of emotional trauma. in Finland, therapy of complex trauma is founded on the
      theory of structural dissociation of the personality, which together with the
      polyvagal theory forms a practical frame of reference for psychotherapeutic work.

PMID- 27044182
TI  - [Fast track bariatric surgery].
AB  - BACKGROUND: Relatively little is known about the use of fast track protocols in
      bariatric surgery. MATERIAL AND METHODS: We carried out an observational study of
      422 consecutive patients who underwent bariatric surgery by a fast track
      protocol. RESULTS: Mean length of stay was 1.3 days, median 1 day. Of all
      patients, 83% were discharged on the first postoperative day. Three patients
      (0.7%) had life-threatening complications. The readmission rate was 4.7%, and
      3.3% of the patients had to be reoperated. The body weight dropped 31% in a year.
      CONCLUSIONS: Early discharge does not seem to increase postoperative morbidity or
      readmissions.

PMID- 27044183
TI  - [When is chest radiography indicated in a child?].
AB  - Chest radiography is the most common radiological examination in children. The
      indications are severe or complicatec pneumonia, exclusion of other diseases when
      diagnosing asthma, and suspected foreign body aspiration if emergency
      bronchoscopy is not performed. Community-acquired pneumonia can be diagnosed on
      the basis of clinical symptoms anc findings alone, but if hospitalization is
      needed for pneumonia, the diagnosis needs to be confirmed with chest radiography
      Imaging is the only reliable method to assess the severity of pneumonia and to
      detect the complications.

PMID- 27044184
TI  - [Surgery-induced abdominal wall nerve entrapment: do not overlook intensive
      postoperative pain].
AB  - The most common cause of persistent postoperative pain after inguinal hernia
      repair is entrapment of a sensory nerve in the wound closure, The pain may be
      triggered by touching the skin, and the pain is relieved after a nerve block. In
      two patient cases, division of the nerve immediately terminated the pain, and the
      relief seemed to be permanent. Pains are common in inguinal hernia scars, but
      also after an appendectomy operation and Pfannenstiel's incision.

PMID- 27044185
TI  - [Update on Current Care Guideline: Parkinson's disease].
AB  - The treatment of Parkinson's disease may be initiated with dopamine agonist or
      MAO-B-inhibitor for people under 60-65 years of age. For older patients, the
      treatment may also be started with levodopa. If there are motor complications,
      such as on-off-symptoms, apomorphin injections can be beneficial in addition to
      other medications. In the case of difficult on-off-symptoms and dyskinesias in
      spite of optimal treatment, deep brain stimulation, duodenal levodopa infusion
      and apomorphine infusion should be considered. Rehabilitation can improve gait
      speed and balance, decrease falls and improve speech. However, with advancing
      disease the results are not maintained if trainino is discontinued.

PMID- 27044186
TI  - Heart matters--a history.

PMID- 27044187
TI  - A lifetime of memories.

PMID- 27044188
TI  - Atrial fibrillation case study.
AB  - This article discusses the irregular heart rhythm caused by atrial fibrillation
      (AF). A brief overview of the pathophysiology will be provided. A case study is
      discussed to highlight the treatment and management of AF. The care provision
      describes common signs and symptoms and also the treatment and management of AF
      within the maternity care setting. The importance of maintaining the mother-baby
      dyad is highlighted. For the purpose of maintaining confidentiality the woman
      will be referred to as Shama.

PMID- 27044189
TI  - Are staffing shortages changing the culture of midwifery?
AB  - The effects of budgetary changes on midwives' practice environment have raised
      concerns in many settings. A survey of midwives and student midwives in the UK
      and Republic of Ireland in 2014 produced 280 responses. Staffing shortages were
      regarded as underpinning many changes, one of which was that of previously
      optional 'extra' activities, such as unpaid overtime, becoming mandatory.
      Shortages were aggravated in less acute areas by the transfer of midwives to more
      acute settings. One of the fears expressed by midwives was that a permanent
      change in the culture of midwifery would result. These phenomena are the everyday
      experiences of practising midwives, but they have failed to be addressed in the
      documents published by regulatory and review bodies.

PMID- 27044190
TI  - Catheterisation: best practice in bladder care.
AB  - Bladder care is an integral part of caring for a woman in labour and the
      immediate postpartum period (National Institute for Health and Care Excellence
      (NICE) 2014a). To ensure effective bladder care, the skill of urinary
      catheterisation is often undertaken by a midwife and can be required in a variety
      of different situations. Catheterisation is a necessary intervention whether it
      is intermittent, indwelling, short-term or, less often, long-term. This article
      addresses the current recommended guidance, highlights best practice measures and
      provides useful hints and tips to support catheter care.

PMID- 27044191
TI  - Midwives, gender equality and feminism.
AB  - Gender inequality and the harmful effects of patriarchy are sustaining the wide
      spread oppression of women across the world and this is also having an impact on
      maternity services with unacceptable rates of maternal mortality, the continued
      under investment in the midwifery profession and the limiting of women's place of
      birth options. However alongside these effects, the current zeitgeist is
      affirming an alignment of feminism and gender equality such that both have a high
      profile in public discourse. This presents a once in a generation opportunity for
      midwives to self-declare as feminists and commit to righting the wrongs of this
      most pernicious form of discrimination.

PMID- 27044193
TI  - The value of reflection.

PMID- 27044192
TI  - Humanising midwifery care.
AB  - Since the publication of the Francis Report (2013), providing care that is kind
      and compassionate is high on the agenda of all NHS services, including maternity.
      This article introduces the humanising values framework that explores aspects of
      what it is to be human and offers practical examples of how it can be
      incorporated into midwifery care. Susan Way and Janet Scammell consider the
      advantages of woman-centred care, highlighting the benefits of humanising care.

PMID- 27044194
TI  - 6. Learning the skill of intravenous cannulation.

PMID- 27044195
TI  - Let there be mood lighting....
AB  - In this column, Sara Wickham takes a sideways look at issues relevant to
      midwives, students, women and families, inviting us to sit down with a cup of tea
      and ponder what we think we know. As it is always useful to consider how we can
      facilitate physiological labour and birth, this month Sara shares some of the
      tips that she has gathered from midwives and other birth workers about how they
      help women and families to lower the light levels and create the semi-darkness
      which many people feel is conducive to normal birth.

PMID- 27044196
TI  - Love matters.

PMID- 27044197
TI  - Ensure Your Choices Have the Right Consequences.

PMID- 27044198
TI  - Be the Change You Want to See in Cancer Care.

PMID- 27044199
TI  - Making Your Voice Heard. How Nurses Can Advocate for Improved Care--at Any Level.

PMID- 27044200
TI  - What Political Issues Will Affect Oncology Nursing in the 2016 Election?

PMID- 27044201
TI  - Nurse Involvement in Grassroots Organizations Leads to Healthcare Reform.

PMID- 27044202
TI  - Patient Education Needs With Pazopanib Therapy for Soft Tissue Sarcoma.

PMID- 27044203
TI  - Cancer Moonshot Task Force Convenes to Tackle Cancer Cure.

PMID- 27044204
TI  - Innovative Clinical Trial Designs Lead to New Drug Approvals.

PMID- 27044205
TI  - New Hazardous Drug Safe Handling Guidelines May Require Changes for Your
      Practice.

PMID- 27044206
TI  - Palliative Care Initiated in the Emergency Department Improves Patients' Quality
      of Life.

PMID- 27044207
TI  - The Case of the Transparent Transport.

PMID- 27044208
TI  - [CORRECTION OF VARUS KNEE WITH REDUCTION OSTEOTOMY DURING TOTAL KNEE
      ARTHROPLASTY].
AB  - OBJECTIVE: To evaluate the effectiveness of reduction osteotomy for correction of
      varus knee during total knee arthroplasty. METHODS: A retrospective analysis was
      made on the clinical data of 16 patients (24 knees) who received reduction
      osteotomy for correcting varus knee during total knee arthroplasty between May
      2010 and July 2012. There were 2 males (3 knees) and 14 females (21 knees), with
      an average age of 67 years (range, 57-79 years). The disease duration ranged from
      3 to 15 years (mean, 9.1 years). The Knee Society Score (KSS) was 38.71 +/- 10.04
      for clinical score and 50.31 +/- 14.31 for functional score. The range of motion
      (ROM) of the knee was (91.88 +/- 13.01). The tibiofemoral angle was (9.04 +/-
      4.53) degrees  of varus deformity. Reduction osteotomy was applied to correct
      varus knee. RESULTS: The operation time was 85-245 minutes (mean, 165.5 minutes);
      the obvious blood loss was 10-800 mL (mean, 183.1 mL); the hospitalization time
      was 8-22 days (mean, 13.6 days). All incisions healed by first intention. No
      neurovascular injury or patellar fracture occurred. The follow-up duration ranged
      from 37 to 62 months (mean, 48 months). The tibiofemoral angle was corrected to
      (3.92 +/- 1.89) degrees  of valgus at 48 hours after operation. The lower limb
      alignment recovered to normal. The X-ray films showed no evidence of obvious
      radiolucent line, osteolysis, or prosthesis subsidence. The results of KSS were
      significantly improved to 84.21 +/- 6.49 for clinical score and 85.31 +/- 6.95
      for functional score (t = 20.665, P = 0.000; t = 9.585, P = 0.000); and ROM of
      the knee was significantly increased to (105.83 +/- 11.29) degrees  (t = 8.333, P
      = 0.000) at last follow-up. CONCLUSION: The effectiveness of reduction osteotomy
      for varus knee deformity during total knee arthroplasty is satisfactory. Proper
      alignment, ROM, and function of knee can be achieved.

PMID- 27044209
TI  - [ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION IN TREATMENT OF OSTEOARTHRITIS AND
      ANTERIOR CRUCIATE LIGAMENT INJURY].
AB  - OBJECTIVE: To explore the short- and mid-term effectivenesses of combined
      unicompartmental knee arthroplasty (UKA) and anterior cruciate ligament (ACL)
      reconstruction for osteoarthritis (OA) and ACL injury. METHODS: Between January
      2006 and January 2014, 32 patients with knee OA and ACL injury were treated by
      combined UKA and ACL reconstruction. There were 12 males and 20 females, aged 41
      63 years (mean, 50 years); 17 left knees and 15 right knees were involved. The
      causes of ACL injury were sports injury (25 cases) and traffic accident injury (7
      cases), including 27 cases of old injury and 5 cases of acute injury. Pain of the
      medial compartment of the knee and unstable knee joint were the main clinical
      symptoms. Preoperative X-ray films showed (3.1 +/- 0.6) degrees  of varus
      deformity. RESULTS: All incisions healed by first intention, without
      complication. The patients were followed up 16-112 months (mean, 55 months).
      Mobile bearing dislocation occurred in 2 cases after operation, and was cured
      after replacing much thicker mobile bearings. X-ray films showed (4.0 +/- 0.7)
      degrees  of valgus at last follow-up. There was no loosening of the prosthesis.
      Physiological radiolucent line (< 1 mm) was observed around the tibial component
      in 10 patients. The Oxford Knee Score (OKS), Knee Society Score (KSS) clinical
      score, KSS functional score, and Tegner activity score at last follow-up were
      improved significantly (P < 0.05). The range of motion (ROM) of the operated knee
      was (123.5 +/- 2.8) degrees , and the posterior slope of the tibial component was
      (3.9 +/- 1.2) degrees  at last follow-up; a significant correlation was found
      between ROM and posterior slope according to the Pearson's correlation (r =
      0.392, P = 0.031). CONCLUSION: Combined UKA and ACL reconstruction has good short
      and mid-term effectivenesses for OA and ACL injury.

PMID- 27044210
TI  - [ARTHROSCOPIC TREATMENT COMBINED WITH REPAIR OF JOINT CAPSULE USING TENDON FLAP
      OF MEDIAL HEAD OF GASTROCNEMIUS MUSCLE AFTER RESECTION OF POPLITEAL CYST].
AB  - OBJECTIVE: To investigate the methods and the effectiveness of arthroscopic
      treatment combined with repair of the cyst wall using the tendon flap of medial
      head of gastrocnemius muscle after resection of popliteal cyst. METHODS: A
      retrospective analysis was made on the clinical data of 140 patients with
      popliteal cyst between August 2009 and June 2014, including 44 males and 96
      females with a mean age of 54.68 years (range, 14-80 years). The median course of
      symptoms was 31 months (range, 20 days to 30 years). According to Rauschning and
      Lindgren criteria for popliteal cyst grade, 4 cases were rated as grade I, 44
      cases as grade II, and 92 cases as grade III. The preoperative Lysholm knee score
      was 68.99 +/- 8.23. Firstly, cyst was resected, then the hernia sac of joint
      capsule was repaired with the tendon flap of medial head of gastrocnemius muscle,
      and finally a knee arthroscopy was used for the diagnosis and treatment of intra
      articular lesions. RESULTS: No complication of nerve or blood vessel injury,
      infection, or necrosis occurred. The mean follow-up was 26 months (range, 6-64
      months). During follow-up, 1 case (0.71%) had cyst recurrence. According to
      Rauschning and Lindgren criteria for popliteal cyst grade, 37 cases were rated as
      grade 0, 92 cases as grade I, 10 cases as grade II, and 1 case as grade III at 6
      months after operation, showing significant difference when compared with
      preoperative one (Z = -14.303, P = 0.000); the Lysholm knee score (85.51 +/-
      9.23) was significantly higher than preoperative score (t= -15.798, P = 0.000).
      CONCLUSION: Arthroscopic treatment combined with repair of the cyst wall with the
      tendon flap of medial head of gastrocnemius muscle after resection of popliteal
      cyst is a better way to avoid recurrence.

PMID- 27044211
TI  - [TREATMENT OF PATELLAR FRACTURES USING Kirschner WITH HOLE AND TENSION BAND
      SYSTEM WITH WIRE WINDING AND PRESSURE].
AB  - OBJECTIVE: To investigate the effectiveness of internal fixation using Kirschner
      with hole and tensionband system with wire winding and pressure in the treatment
      of patellar fracture. Methods Between February 2008 andJanuary 2010, 39 patients
      with patellar fracture were treated using Kirschner with hole and tension band
      system with wire winding and pressure. The average age was 37 years (range, 18-65
      years), including 23 males and 16 females. The left side was involved in 21 cases
      and the right side in 18 cases. The causes were falling injury in 21 cases,
      traffic accident injury in 11 cases, and striking injury in 7 cases. The injury
      to operation time was 5 hours to 6 days (mean, 3.5 days). Twelve cases had open
      fractures, and 19 cases had comminuted fractures. RESULTS: All incisions healed
      by first intention, and no deep venous thrombosis of lower limbs formed. Thirty
      nine patients followed up 12-21 months (mean, 14 months). There was no wire
      breaking during operation and after operation. X-ray film showed no re-fracture,
      fracture displacement, or needle displacement; fracture healed well, fracture
      line disappeared at 6-8 weeks (mean, 7.5 weeks) after operation. After 12 months,
      the internal fixation was removed; according to the Lysholm knee score standard,
      the results were excellent in 22 cases, good in 16 cases, fair in 1 case, and the
      excellent and good rate was 97.4%. CONCLUSION: Internal fixation using Kirschner
      with hole and tension band system with wire winding and pressure has satisfactory
      effectiveness for the treatment of patellar fracture, with the following
      advantages: wire is not easy to break, the needle does not fall off, and the
      pressure strength is powerful.

PMID- 27044212
TI  - [APPLICATION OF COMPUTER-ASSISTED SURGICAL PLANNING IN SURGICAL TREATMENT OF
      ANKLE FRACTURES].
AB  - OBJECTIVE: To explore the clinical value of computer-assisted surgical planning
      in the treatment of ankle fractures. METHODS: Between January 2012 and January
      2014, open reduction and internal fixation were performed on 42 patients with
      ankle fractures. There were 22 males and 20 females with an average age of 52
      years (range, 19-72 years). The causes were spraining injury (20 cases), traffic
      accident injury (14 cases), and falling from height injury (8 cases). The time
      from injury to operation was 5 hours to 12 days (mean, 2.5 days). All fractures
      were closed trimalleolar fractures. According to Lauge-Hansen classification, 25
      cases were rated as supination extorsion type IV, 13 as pronation extorsion type
      IV, and 4 as pronation abduction type III. The preoperative planning was made by
      virtual reduction and internal fixation using Superimage software. RESULTS: The
      mean operation time was 93.7 minutes (range, 76-120 minutes). Delayed wound
      healing occurred in 1 case, and secondary healing was obtained after treatment;
      primary healing of incision was achieved in the other patients. Postoperative X
      ray films and CT images showed anatomic reduction of fracture and good position
      of internal fixation. All patients were followed up 14.6 months on average
      (range, 9-27 months). The range of motion of the affected ankle was close to the
      normal side at 6-8 weeks. The mean fracture healing time was 13.1 weeks (range,
      11-17 weeks). Degenerative change of the ankle joint was observed in 3 cases
      (7.1%) with manifestation of mild narrowing of joint space on the X-ray films at
      last follow-up. According to Baird-Jackson score system, the results were
      excellent in 24 cases, good in 13 cases, and fair in 5 cases, with an excellent
      and good rate of 88%. CONCLUSION: Computer-assisted surgical planning for ankle
      fractures can help surgeons identify type of ankle fractures and improve surgical
      scheme for guiding fracture reduction and selecting and placing implants, so good
      effectiveness can be obtained.

PMID- 27044213
TI  - [Ilizarov TECHNOLOGY COMBINED WITH TARSAL V-SHAPE OSTEOTOMY FOR TREATMENT OF
      TRAUMATIC CLUBFOOT].
AB  - OBJECTIVE: To discuss the effectiveness of Ilizarov technology combined with
      tarsal V-shape osteotomy for the treatment of traumatic clubfoot. METHODS:
      Between August 2011 and August 2014, 14 patients with traumatic clubfoot were
      treated. There were 10 males and 4 females, aged 13 to 61 years (mean, 31 years).
      of 14 cases, 11 had open fractures of the tibia and ankle and 3 had closed
      fracture of the ankle joint. The interval from trauma to operation was 7-78
      months (mean, 36 months). The plantar flexion of the ankle was 44-89 degrees 
      (mean, 57 degrees ). After invasive foot soft tissue release and tarsal V-shape
      osteotomy, the Ilizaroy external fixator with elastic stretching rod was used. At
      5-12 weeks after operation, the neutra pos ofthe ankle joint was restored. Then
      the neutral position of the ankle joint was maintained for 8 to 12 weeks. After
      removal of external fixator, protective walking brace was used for 8 to 12 weeks.
      RESULTS: Infection occurred in 9 cases, and was cured after symptomatic
      treatment. The patients were followed up 10-36 months (mean, 15 months). After
      treatment, 14 patients had normal appearance of the ankle joint, and X-ray films
      showed normal structure of the ankle. The ankle dorsal extension was 10 degrees 
      in 9 patients, who had normal walking function; it was 5 degrees  in 4 patients,
      who could walk; in 1 case of neutral position, the foot had no function of up and
      down stairs. One case had pain during correction because of poor tolerance, and
      delay traction was given, the function was recovered to normal after active
      rehabilitation training. According to the International Clubfoot Study Group
      (ICFSG) score standard, the results were excellent in 9 cases, good in 4 cases,
      and fair in 1 case; the excellent and good rate was 92.9% at last follow-up.
      CONCLUSION: Ilizarov external fixation combined with V-shape osteotomy is
      effective for the treatment of traumatic clubfoot, with the advantages of less
      trauma, reliable fixation, satisfactory correction of the deformity, and good
      function recovery of the ankle.

PMID- 27044214
TI  - [PERCUTANEOUS Kirschner WIRE POKING REDUCTION AND ELASTIC STABLE INTRAMEDULLARY
      NAILING FIXATION FOR SEVERE DISPLACED RADIAL NECK FRACTURES IN CHILDREN].
AB  - OBJECTIVE: To assess the effectiveness of percutaneous Kirschner wire poking
      reduction and elastic stable intramedullary nailing fixation for treating severe
      displaced radial neck fractures in children. METHODS: Between November 2010 and
      August 2014, 17 children with severe displaced radial neck fractures were treated
      with percutaneous Kirschner wire poking reduction and elastic stable
      intramedullary nailing fixation. There were 13 boys and 4 girls with an average
      age of 8.7 years (range, 6-14 years). The right side was involved in 9 cases, and
      the left side was involved in 8 cases. The causes of injury were falling in all
      cases. The angular deformity at fracture was 64-102 degrees  (mean, 84 degrees ).
      According to the Judet classification, 7 cases were classified as grade IVa and
      10 cases as grade IVb. The time from injury to operation was 4.2 days (range, 1-7
      days). Metaizeau classification and Tibone-Stoltz elbow performance score were
      used to access the radiological and clinical results, respectively. RESULTS: The
      operation time was 20-50 minutes (mean, 30 minutes). All incisions healed by
      first intention. The patients were followed up 12-46 months (mean, 20 months).
      All fractures healed at 2 months after operation. There was no complication of
      malunion, early epiphyseal closure, avascular necrosis, enlargement of the radial
      head epiphysis, cubitus varus and valgus deformities, or proximal radioulnar
      joint synostosis. One case had elbow extension limitation. At last follow-up, the
      elbow range of motion in flexion, extension, pronation, and supination showed no
      significant difference between affected side and normal side (P>0.05). The
      clinical results were excellent in 16 cases and good in 1 case, with an excellent
      and good rate of 100%. The angulation was 0-12 degrees  (mean, 3.7 degrees ) on
      the X-ray film; anatomic reduction or nearly anatomic reduction was obtained, and
      the radiological results were excellent in 13 cases and good in 4 cases, with an
      excellent and good rate of 100%. CONCLUSION: Percutaneous Kirschner wire poking
      reduction followed by fixation with elastic stable intramedullary nailing is a
      simple, safe, minimally invasive, and effective method to treat severe displaced
      radial neck fractures in children.

PMID- 27044215
TI  - [EFFECTIVENESS OF Ilizarov TECHNIQUE IN TREATMENT OF OLD DISLOCATION OF RADIAL
      HEAD].
AB  - OBJECTIVE: To explore the effectiveness of modified Ilizarov semi-ring external
      fixator combined with an ulnar osteotomy lengthening in the treatment of old
      dislocation of the radial head in children. METHODS: A retrospective analysis was
      made on the data of 14 patients with old dislocation of the radial head treated
      by the modified Ilizarov semi-ring external fixator combined with ulnar osteotomy
      lengthening between March 2012 and January 2015. The age ranged from 2 to 13
      years (mean, 7.2 years), including 12 boys and 2 girls. There was 1 case of
      congential dislocation of the radial head and 13 cases of old Monteggia fracture.
      According to the Bado's classification, dislocation was rated as grade I in 12
      cases and grade III in 2 cases. The elbow flexion-extension and forearm pronation
      and supination were compared between at pre- and post-operation; Mackay
      evaluation standard of elbow joint function was used to evaluate the
      effectiveness. RESULTS: The operation time ranged from 50 to 65 minutes (mean, 58
      minutes). All patients were followed up 6-33 months (mean, 21 months). No
      complication of infection, myositis ossificans, or re-dislocation occurred. X-ray
      film showed bony healing at ulnar osteotomy site within 82-114 days (mean, 90
      days). The elbow flexion-extension and forearm pronation and supination were
      significantly improved at postoperation when compared with preoperation (P <
      0.05). The results of Mackay function assessment were excellent in 12 cases and
      good in 2 cases. CONCLUSION: The modified Ilizarov semi-ring external fixator
      combined with an ulnar osteotomy lengthening has the advantages of small
      incision, easy removal of fixator, satisfactory reduction, and no nonunion at
      ulnar osteotomy site in the treatment of old dislocation of the radial head, but
      the long-term effectiveness still needs to be followed up.

PMID- 27044216
TI  - [EFFECT OF HAMSTRING TENDON TRANSFECTED WITH ADENOVIRUS- MEDIATED TRANSFORMING
      GROWTH FACTOR beta1 GENE ON HISTOMORPHOLOGY OF TENDON-BONE INTERFACE HEALING
      AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION IN RABBITS].
AB  - OBJECTIVE: To investigate the effect of hamstring tendon transfected with
      adenovirus-mediated transforming growth factor beta1 (AdTGF-beta1) genes on the
      histomorphology of tendon-bone interface healing after anterior cruciate ligament
      (ACL) reconstruction in rabbits. METHODS: AdTGF-beta1 and AdGFP were diluted to 5
      x 108 PFU/mL with DMEM. Forty-eight New Zealand white rabbits were divided into 3
      groups randomly (n=16), weighing 1.6-2.5 kg for ACL reconstruction with hamstring
      tendon autograft. Hamstring tendon was cultured and transfected with AdTGF-beta1
      (group A) and AdGFP (group B) for 12 hours before ACL reconstruction, and was
      cultured with DMEM in group C. After 12 hours of transfection, the expression of
      green fluorescence was observed in groups A and B under fluorescence microscopy;
      TGF-beta1 protein level was detected by ELISA in group A. At 2, 4, 8, and 12
      weeks after operation, the specimens were harvested for HE and Masson staining;
      the number of fibroblasts was counted, and the Buark grading was used to evaluate
      tendon-bone interface healing. RESULTS: Green fluorescence was observed after 12
      hours of transfection in groups A and B. TGF-beta1 protein level reached (221.0
      +/- 12.2) ng/mL at 12 hours in group A. The histological observation showed that
      few fibroblasts and collagen fibers were found, and Sharpey fibers appeared in
      group A; regular Sharpey fibers were seen in the interface, and integrity
      interface in some areas at 12 weeks. But fibroblasts of groups B and C were less
      than those of group A, with loose tendon-bone interface; no integrity interface
      was observed at 12 weeks. The number of fibroblasts and Buark grading of group A
      were significantly higher than those of groups B and C (P < 0.05), but no
      significant difference was found between groups B and C (P > 0.05). CONCLUSION:
      Hamstring tendon transfected with AdTGF-beta1 gene can promote the healing of
      tendon-bone interface after ACL reconstruction.

PMID- 27044217
TI  - [IN VIVO THREE-DIMENSIONAL TRANSIENT MOTION CHARACTERISTICS OF THE SUBAXIAL
      CERVICAL SPINE IN HEALTHY ADULTS].
AB  - OBJECTIVE: To observe the in vivo three-dimensional (3-D) transient motion
      characteristics of the subaxial cervical spine in healthy adults. METHODS:
      Seventeen healthy volunteers without cervical spine related diseases were
      recruited for this study, including 8 males and 9 females with a mean age of 26
      years (range, 23-41 years). The vertebral segment motion of each subject was
      reconstructed with CT, and Rhinoceros 4.0 solid modeling software were used for 3
      D reconstruction model of the subaxial cervical spine. In vivo cervical vertebral
      motion in flexion-extension, left and right bending, left and right rotation was
      observed with dual fluoroscopic imaging system (DFIS). Coordinate systems were
      established at the vertebral center of C3-7 to obtain the intervertebral range of
      motion (ROM) and displacement at C3,4, C4,5, C5,6, and C6,7. The X-axis pointed
      to the left along the coronal plane, the Y-axis pointed to the back along the
      sagittal plane, and the Z-axis perpendicular to the X-Y plane pointed to the
      head. The ROM along X, Y, and Z axises were represented by rotation in flexion
      extension (alpha), in left-right bending (beta), and in left-right twisting (y)
      respectively, and the displacement in left-right direction (x), in anterior
      posterior direction (y), and in proximal-distal direction (z), respectively.
      RESULTS: In flexion and extension, the displacement in anterior-posterior
      direction of C6,7 was significantly less that of other segments (P < 0.05), but
      the displacements in left-right direction and in proximal- distal direction
      showed no significant difference between segments (P > 0.05); the ROM values in
      flexion-extension of C4,5 and C5,6 were significantly larger than those of C3,4
      and C6,7 (P < 0.05), and the ROM value in left-right twisting of C4,5 was
      significantly larger than those of C5,6 and C6,7 (P < 0.05), but the ROM value in
      left-right bending showed no significant difference between segments (P > 0.05).
      In left and right bending, there was no significant difference in the
      displacement between other segments (P > 0.05) except that the displacement in
      anterior-posterior direction of C3,4 was significantly larger than that of C4,5
      (P< 0.05), and that the displacement in proximal-distal direction of C6,7 was
      significantly less than that of C3,4 and C4,5 (P < 0.05); no significant
      difference was shown in the ROM value between segments (P > 0.05), except that
      the ROM value in left-right twisting of C3,4 was significantly larger than that
      of C5,6 and C6,7 (P < 0.05). In left and right rotation, the ROM value in left
      right twisting of C3,4 was significantly larger than that of C4,5 and C6,7 (P <
      0.05), and the displacement and ROM value showed no significant differece between
      other segments (P > 0.05). CONCLUSION: The intervertebral motions of the cervical
      spine show different characters at different levels. And the 6-degree-of-freedom
      data of the cervical vertebrae are obtained, these data may provide new
      information for the in vivo kinematics of the cervical spine.

PMID- 27044218
TI  - [POSTERIOR LUMBAR INTERBODY FUSION FOR DOUBLE-SEGMENTAL BILATERAL ISTHMIC LUMBAR
      SPONDYLOLISTHESIS].
AB  - OBJECTIVE: To explore the effectiveness of posterior lumbar interbody fusion in
      the treatment of double-segmental bilateral isthmic lumbar spondylolisthesis.
      METHODS: Between February 2008 and December 2013, 17 patients with double
      segmental bilateral isthmic lumbar spondylolisthesis were treated with posterior
      lumbar interbody fusion. There were 12 males and 5 females, with an age ranged 48
      69 years (mean, 55.4 years). The disease duration ranged from 11 months to 17
      years (median, 22 months). According to the Meyerding classification, 30
      vertebrea were rated as degree I, 3 as degree II, and 1 as degree III. L4,5 was
      involved in 14 cases and L3,4 in 3 cases. The preoperative visual analogue scale
      (VAS) score was 8.6 +/- 3.2. RESULTS: Cerebrospinal fluid leakage occurred in 2
      cases because of intraoperative dural tear; primary healing of incision was
      obtained, with no operation related complication in the other patients. The
      patients were followed up 1-6 years (mean, 3.4 years). At last follow-up, VAS
      score was decreased significantly to 1.1 +/- 0.4, showing significant difference
      when compared with preoperative score (t=7.652, P=0.008). X-ray films showed that
      slippage vertebral body obtained different degree of reduction, with a complete
      reduction rate of 85% (29/34) at 1 week after operation. All patients achieved
      bony union at 6-12 months (mean, 7.4 months). According to the Lenke
      classification, 13 cases were rated as grade A and 4 cases as grade B. No
      internal fixation loosening and fracture were observed during the follow-up.
      Intervertebral disc height was maintained, no loss of spondylolisthesis reduction
      was found. CONCLUSION: It can obtain satisfactory clinical result to use spinal
      canal decompression by posterior approach, and screw fixation for posterior
      fusion in treatment of double-segmental bilateral isthmic lumbar
      spondylolisthesis. The key points to successful operation include accurate
      insertion of screw, effective decompression, distraction before reduction,
      rational use of pulling screws, and interbody fusion.

PMID- 27044219
TI  - [COMPARISON OF EFFECTIVENESS AND CHANGE OF SAGITTAL SPINO-PELVIC PARAMETERS
      BETWEEN MINIMALLY INVASIVE TRANSFORAMINAL AND CONVENTIONAL OPEN POSTERIOR LUMBAR
      INTERBODY FUSIONS IN TREATMENT OF LOW-DEGREE ISTHMIC LUMBAR SPONDYLOLISTHESIS].
AB  - OBJECTIVE: To compare the effectiveness and changes of sagittal spino-pelvic
      parameters between minimally invasive transforaminal lumbar interbody fusion and
      conventional open posterior lumbar interbody fusion in treatment of the low
      degree isthmic lumbar spondylolisthesis. METHODS: Between May 2012 and May 2013,
      86 patients with single segmental isthmic lumbar spondylolisthesis (Meyerding
      degree I or II) were treated by minimally invasive transforaminal lumbar
      interbody fusion (minimally invasive group) in 39 cases, and by open posterior
      lumbar interbody fusion in 47 cases (open group). There was no significant
      difference in gender, age, disease duration, degree of lumbar spondylolisthesis,
      preoperative visual analogue scale (VAS) score, and Oswestry disability index
      (ODI) between 2 groups (P>0.05). The following sagittal spino-pelvic parameters
      were compared between 2 groups before and after operation: the percentage of
      slipping (PS), intervertebral height, angle of slip (AS), thoracolumbar junction
      (TLJ), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis
      (SVA), spino-sacral angle (SSA), sacral slope (SS), pelvic tilt (PT), and pelvic
      incidence (PI). Pearson correlation analysis of the changes between pre- and post
      operation was done. RESULTS: Primary healing of incision was obtained in all
      patients of 2 groups. The postoperative hospital stay of minimally invasive group
      [(5.1 +/- 1.6) days] was significantly shorter than that of open group [(7.2 +/-
      2.1) days] (t = 2.593, P = 0.017). The patients were followed up 11-20 months
      (mean, 15 months). The reduction rate was 68.53% +/- 20.52% in minimally invasive
      group, and was 64.21% +/- 30.21% in open group, showing no significant difference
      (t = 0.725, P = 0.093). The back and leg pain VAS scores, and ODI at 3 months
      after operation were significantly reduced when compared with preoperative ones
      (P < 0.05), but no significant difference was found between 2 groups (P > 0.05).
      The postoperative other sagittal spino-pelvic parameters were significantly
      improved (P < 0.05) except PI (P > 0.05), but there was no significant difference
      between 2 groups (P > 0.05). The correlation analysis showed that ODI value was
      related to the SVA, SSA, PT, and LL (P < 0.05). CONCLUSION: Both minimally
      invasive transforaminal lumbar interbody fusion and conventional open posterior
      lumbar interbody fusion can significantly improve the sagittal spino-pelvic
      parameters in the treatment of low-degree isthmic lumbar spondylolisthesis. The
      reconstruction of SVA, SSA, PT, and LL are related to the quality of life.

PMID- 27044220
TI  - [RECONSTRUCTION OF IRREGULAR DEFECTS OF HAND USING LATERAL ARM FREE PERFORATOR
      FLAP BY PERSONALIZED DESIGN].
AB  - OBJECTIVE: To observe the effectiveness of lateral arm free perforator flap by
      personalized design in repairing irregular defects of the hand. METHODS: Twelve
      patients with irregular defects of the hand were repaired with lateral arm free
      perforator flaps by personalized design between January 2010 and January 2015.
      There were 7 males and 5 females with a mean age of 35 years (range, 18-52
      years). The causes included crush injury in 5 cases, thermal injury in 3 cases,
      traffic accident injury in 2 cases, and friction injury in 2 cases. The time
      between injury and admission was 1.0-4.5 hours (mean, 3.1 hours). In 3 patients
      with skin and soft tissue defect of approximate square, the flap of less than 6
      cm in width was designed and was segmented into foliated flaps to repair wound;
      the bilobed flaps were used in 5 cases of hand penetrating wounds; the bilobed
      flaps or trifoliate flaps were used in 4 cases of multiple finger skin soft
      tissue defects. The total area of the defects ranged from 6.0 cm x 5.0 cm to 9.0
      cm x 8.0 cm, and the area of flap ranged from 10.0 cm x 3.5 cm to 12.0 cm x 6.0
      cm. All the wounds at donor site were closed directly. RESULTS: All the flaps
      survived, wounds and incisions at donor sites healed by first intention. The
      patients were followed up 6-15 months (mean, 10 months). Bulky flaps were
      observed in 2 cases of female patients, and flap thinning was performed at 3
      months after operation. The hand function recovered satisfactorily, and the
      sensation was 51-53 at 6 months after operation. According to the functional
      assessment criteria of upper limb formulated by the Hand Surgery Branch of
      Chinese Medical Association, the results were excellent in 2 cases, good in 7
      cases, fair in 2 cases, and poor in 1 case. The linear scars was observed at the
      donor site. CONCLUSION: The lateral arm free perforator flap has constant vessels
      anatomy, and there are many perforators in the intermuscular septum. The lateral
      arm free perforator flap by personalized design can repair irregular defects of
      the hand.

PMID- 27044221
TI  - [APPLICATION OF V-Y ADVANCED SENSE-REMAINED POSTERIOR TIBIAL ARTERY PERFORATOR
      FLAP IN REPAIRING WOUND AROUND ANKLE].
AB  - OBJECTIVE To explore the feasibility and effectiveness of V-Y advanced sense
      remained posterior tibial artery perforator flap in repairing wound around the
      ankle. METHODS Between March 2012 and January 2015, 11 patients with wounds
      around the ankle were treated by V-Y advanced sense-remained posterior tibial
      artery perforator flap. There were 6 males and 5 females with a median age of 37
      years (range, 21-56 years). The causes were traffic accident injury in 3 cases,
      thermal injury in 2 cases, burn in 2 cases, iatrogenic wounds in 2 cases, and
      local contusion in 2 cases. The disease duration ranged from 1 to 3 weeks (mean,
      2 weeks). Injury was located at the medial malleolus in 4 cases, at the lateral
      malleolus in 3 cases, and at the heel in 4 cases. All had exposure of bone,
      tendon, or plate. The defect area ranged from 4 cmx2 cm to 5 cmx3 cm; the area of
      the flap ranged from 11 cmx4 cm to 15 cmx6 cm. RESULTS: Necrosis of distal flap
      occurred in 1 case after operation; re-operation to amputate the posterior tibial
      artery was given and the wound was repaired by proximal skin graft. Light
      necrosis of distal end was observed in 2 cases, and wound healed at 3 weeks after
      dressing. And other flaps successfully survived, and primary healing of wounds
      were obtained. The patients were followed up 6-24 months (mean, 11 months). The
      flaps were good in color, texture, and appearance. The ankle joint had normal
      activity. At last follow-up, 10 cases restored fine sense, and 1 case restored
      protective feeling with posterior tibial artery advanced flap after amputation.
      CONCLUSION: V-Y advanced sense-remained posterior tibial artery perforator flap
      has the advantages of reliable blood supply, simple operation, good appearance,
      and sensory recovery. Therefore, it is an ideal method to repair wound around the
      ankle.

PMID- 27044222
TI  - [APPLICATION OF FREE BILOBED MEDIAL SURAL ARTERY PERFORATOR FLAP FOR REPAIRING
      PENETRATING WOUND OF FOOT].
AB  - OBJECTIVE: To explore the effectiveness of the free bilobed medial sural artery
      perforator (BMSAP) flap to repair penetrating wound of the foot. METHODS: Between
      April 2012 and October 2014, 7 cases of foot penetrating wounds were treated with
      the BMSAP flap. There were 5 males and 2 females, aged from 21 to 43 years (mean,
      31.5 years). The causes of injury included the crush injury (4 cases), blunt
      puncture (2 cases), and firearm injury (1 case). The wound was located at the
      left foot in 4 cases and at the right foot in 3 cases. There were longitudinal
      penetrating injury in 5 cases and transverse penetrating injury in 2 cases. The
      size of wound ranged from 4 cm x 3 cm to 9 cm x 7 cm. The interval between injury
      and admission was 0.5-5.5 hours (mean, 3.2 hours). The free BMSAP flap of 5 cm x
      4 cm-10 cm x 8 cm in size was used to repair the wounds on both sides and to
      reconstruct the sensation. The donor site was sutured or repaired with skin
      graft. RESULTS: After operation, 1 case had distal flap necrosis, the flap
      survived after dressing change; 1 case had wound infection, and delayed healing
      was obtained after drainage; and the flap survived completely, and primary
      healing was obtained in the other 5 cases. The skin grafts survived and healing
      of incision by first intention was observed at donor sites. The patients were
      followed up from 7 to 24 months (mean, 12.5 months). The flap had soft texture
      and similar color to normal skin. According to the British Medical Research
      Council (BMRC) sensory function assessment system, 1 case was rated as S2, 4
      cases as , and 2 cases as S3+. The American Orthopaedic Foot and Ankle Society
      (AOFAS) score was 86-97 (mean, 93.6); the results were excellent in 6 cases and
      good in 1 case. CONCLUSION: The free BMSAP flap is very suitable to repair
      penetrating wound of the foot. The flap has the advantages of repairing the two
      wounds at the same time and reconstructing skin sensation as well.

PMID- 27044223
TI  - [EFFECT OF INFECTION ON CAPSULE FORMATION AFTER BREAST IMPLANTS].
AB  - OBJECTIVE: To investigate the correlation between infection and capsular
      contracture by observing the effect of infection on the formation of the
      surrounding capsule after breast implants. METHODS: Three healthy adult female
      Diannan small-ear pigs underwent augmentation mammaplasty using miniature
      implants, which were randomly divided into group A (12 nipples), group B (10
      nipples), and group C (12 nipples). Staphylococcus epidermidis (SE ATCC12228 and
      SE RP62A, 1.2 x 105 CFU/mL) was inoculated into the periprosthetics of groups B
      and C, and sterile PBS in group A before breast implants. Then the silica gel
      prosthesis was put, total 34 implants in 3 groups. After 13 weeks, the capsule
      was harvested to measure the capsular tension and weight. HE staining was used to
      observe the structure characteristics of the capsule and to measure the capsule
      thickness, Van-Gieson (VG) staining to observe the capsule collagen
      characteristics, and alpha-smooth muscle actin (alpha-SMA) immunocytochemistry
      staining to observe myofibroblasts in capsule. RESULTS: Primary healing of
      incision was obtained, and 3 small-ear pigs showed stable life indication. The
      complete fibrous capsule was observed after 13 weeks in 3 groups. Capsule tension
      showed no significant difference among 3 groups (P > 0.05). Capsule weight was
      significantly greater in group C than in groups A and B (P < 0.05). HE staining
      showed that capsule structure of the 3 groups was similar with obvious dense
      layer and loose layer, and the capsule thickness was also significantly greater
      in group C than in groups A and B (P < 0.05), but no significant difference was
      found between groups A and B (P > 0.05). VG staining showed that collagenous
      fiber in the capsule were more compact in group C than in groups A and B. The
      alpha-SMA immunocytochemistry staining indicated the myofibroblasts in capsule
      were the most in group C. CONCLUSION: Infection after breast implants has obvious
      impacts on the formation of the capsule, and there was a causal link between
      infection and capsular contracture.

PMID- 27044224
TI  - [RECONSTRUCTION OF LOWER EXTREMITY FUNCTION OF COMPLETE SPINAL CORD INJURY RATS
      BY FIRST NEURON CONNECTION].
AB  - OBJECTIVE: To investigate the effects of the first neuron connection for the
      reconstruction of lower extremity function of complete spinal cord injury rats.
      METHODS: Forty adult female Sprague Dawley rats of 300-350 g in weight were
      selected to prepare the models of L1 transverse spinal cord injury. After 2 weeks
      of establishing model, the rats were randomly divided into control group (n = 20)
      and experimental group (n = 20). In the experimental group, the right hind limb
      function was reconstructed directly by the first neuron; in the control group,
      the other treatments were the same to the experimental group except that the
      distal tibial nerve and the proximal femoral nerve were not sutured. The recovery
      of motor function of lower extremity was observed by the Basso-Beattie-Bresnahan
      (BBB) scoring system on bilateral hind limbs at 7, 30, 50, and 70 days after
      operation. The changes of the spinal cord were observed by HE staining,
      neurofilament 200 immunohistochemistry staining, and the technique of horseradish
      peroxidase (HRP) tracing. RESULTS: After establishing models, 6 rats died. The
      right hind limb had no obvious recovery of the motor function, with the BBB score
      of 0 in 2 groups; the left hind limb motor function was recovered in different
      degrees, and there was no significant difference in BBB score between 2 groups (P
      > 0.05). In the experimental group, HE staining showed that the spinal cord was
      reconstructed with the sciatic nerve, which was embedded in the spinal cord, and
      the sciatic nerve membrane was clearly identified, and there was no obvious
      atrophy in the connecting part of the spinal cord. In the experimental group, the
      expression of nerve fiber was stained with immunohistochemistry, and the axons of
      the spinal cord were positively by stained and the peripheral nerve was connected
      with the spinal cord. HRP labelled synapses were detected by HRP retrograde
      tracing in the experimental group, while there was no HRP labelled synapse in the
      control group. CONCLUSION: Direct reconstruction of the first neurons is
      sufficient in the regeneration of corresponding neural circuit by the growth of
      residual axon; but the motor function recovery of the target muscles innervated
      by peripheral nerve is not observed.

PMID- 27044225
TI  - [A PRELIMINARY STUDY ON SMALL INTESTINAL SUBMUCOSA-SILK COMPOSITE SCAFFOLD TO
      RECONSTRUCT ANTERIOR CRUCIATE LIGAMENT].
AB  - OBJECTIVE: To prepare the small intestinal submucosa (SIS)-silk composite
      scaffold for anterior cruciate ligament (ACL) reconstruction, and to evaluate its
      properties of biomechanics, biocompatibility, and the influence on synovial fluid
      leaking into tibia tunnel so as to provide a better choice in the clinical
      application of ACL reconstruction. METHODS: The silk was used to remove sericin
      and then weaved as silk scaffold, which was surrounded cylindrically by SIS to
      prepare a composite scaffold. The property of biomechanics was evaluated by
      biomechanical testing system. The cell biocompatibility of scaffolds was
      evaluated by live/dead staining and the cell counting kit 8 (CCK- 8). Thirty 6
      week-old Sprague Dawley rats were randomly assigned to 2 groups (n = 15). The
      silk scaffold (S group) and composite scaffold (SS group) were subcutaneously
      implanted. At 2, 4, and 8 weeks after implanted, the specimen were harvested for
      HE staining to observe the biocompatibility. Another 20 28-week-old New Zealand
      white rabbits were randomly assigned to the S group and SS group (n = 20), and
      the silk scaffold and composite scaffold were used for ACL reconstruction
      respectively in 2 groups. Furthermore, a bone window was made on the tibia
      tunnel. At last, the electric resistance of tendon graft in the bone window was
      measured and recorded at different time points after 5 mL of 10% NaCl or 5 mL of
      ink solution was irrigated into the joint cavity recspectively. RESULTS: The
      gross observation showed that the composite scaffold consisted of the helical
      silk bundle inside which was surrounded by SIS. The maximal load of silk scaffold
      and composite scaffold was respectively (138.62 +/- 11.41) N and (137.05+/-
      16.95) N, showing no significant difference (P > 0.05); the stiffness was
      respectively (24.65 +/- 2.62) N/mm and (24.21 +/- 2.39) N/mm, showing no
      significant difference (P > 0.05). The live/dead staining showed that the cells
      had good activity on both scaffolds. However, the cells on the composite scaffold
      had better extensibility. In addition, the cell proliferation curve indicated
      that no significant difference in the absorbance (A) values was founded between
      groups at various time points (P > 0.05). HE staining showed less inflammatory
      cells and much more angiogenesis in SS group than in S group at 2, 4, and 8 weeks
      after subcutaneously implanted (P < 0.05), indicating good biocompatibility.
      Additionally, the starting time points of electric resistance decrease and the
      ink leakage were both significantly later in SS group than in S group (P < 0.05).
      The duration of ink leakage was significantly longer in SS group than in S group
      (P < 0.05). CONCLUSION: The SIS-silk composite scaffold has excellent
      biomechanical properties and biocompatibility and early vacularization after in
      viva implantation. Moreover, it can reducing the leakage of synovial fluid into
      tibia tunnel at the early stage of ACE reconstruction. So it is promising to be
      an ideal ACL scaffold.

PMID- 27044226
TI  - [EFFECT OF ADIPOSE-DERIVED STEM CELLS COMBINED WITH CHITOSAN ON IMMEDIATE
      RETRACTION RATE OF EXPANDED SKIN IN RABBIT].
AB  - OBJECTIVE: To investigate the effect of adipose-derived stem cells (ADSCs)
      combined with chitosan on the immediate retraction rate of rabbit expanded skin.
      METHODS: ADSCs were isolated from rabbit fresh fat under sterile conditions and
      cultured to the 3rd generation by methods of enzymatic digestion; the specific
      surface markers and the differentiation into epidermal cells and cartilage cells
      were identified. Forty New Zealand white rabbits (aged, 2-3 months) were randomly
      divided into 4 groups (n = 10): control group (group A), ADSCs group (group B),
      chitosan group (group C), and ADSCs+chitosan group (group D). ADSCs cell
      suspension with the concentration of 5 x 106 cells/mL was prepared. The skin
      expansion model was made by embedding 30 mL dilator into the back of rabbit.
      Chitosan (2%, 5 mL) was coated on the surface of the dilator in groups C and D,
      and ADSCs cell suspension (1 mL) was injected into the skin in groups B and D.
      Conventional tissue expansion was performed to expected capacity at 4 weeks, and
      maintained for 1 week. The expanded skin was harvested to measure the immediate
      retraction rate, and the thickness of skin, epidermis, and fibrous capsule with
      HE staining. Masson staining was used to observe the characteristics of collagen
      in the fibrous capsule, and immunohistochemical staining for CD31 to determine
      the microvessel density (MVD). RESULTS: ADSCs were successfully isolated, and had
      multiple differentiation ability. All the animals survived to the end of the
      experiment. The immediare retraction rate of group D was significantly lower than
      that of the other groups (P < 0.05), groups B and C were significantly lower than
      group A (P < 0.05), and group B was significantly lower than group C (P < 0.05).
      The histological staining revealed that there were more mature fibroblasts and
      coarse collagen fibers with regular arrangement in groups A and B; there were
      more naive fibroblasts and tiny and sparse collagen fibers in groups C and D. The
      thickness of skin and epidermis, and MVD of groups B and D were significantly
      larger than those of groups A and C (P < 0.05); the thickness of fibrous capsule
      of groups C and D was significantly less than that of groups A and B (P < 0.05);
      but no significant difference was found in the above indexes between other groups
      (P > 0.05). CONCLUSION: ADSCs can promote angiogenesis and regeneration of the
      expanded skin, have no effect on the fibrous capsule. Chitosan can inhibit the
      proliferation of fibrous capsule, so a combination of ADSCs and chitosan can
      inhibit the immediate retraction of the expanded skin.

PMID- 27044227
TI  - [EFFECT OF INHIBITOR OF DIFFERENTIATION 1 GENE TRANSFECTION ON BONE MORPHOGENETIC
      PROTEIN 2 PROMOTING CHONDROGENIC GENE EXPRESSIONS OF RABBIT INTERVERTEBRAL
      CARTILAGE ENDPLATE CELLS].
AB  - OBJECTIVE: To study the effect of inhibitor of differentiation 1 (Id1) gene
      transfection on bone morphogenetic protein 2 (BMP-2) promoting the expressions of
      collagen type II (COL II) and aggrecan (ACAN) in intervertebral cartilage
      endplate cells (EPCs). METHODS: EPCs were harvested from the New Zealand white
      rabbits, the 2nd generation EPCs were used for experiment. The transfection
      efficiency of green fluorescent protein blank lentivirus, high expression of Id1
      lentivirus, RNA interference (RNAi) Id1 lentivirus transfection in the EPCs were
      observed by the fluorescence microscopy, real-time fluorescence quantitative PCR,
      and Western blot. Blank vector, single BMP-2 gene, BMP-2 and Id1 genes were
      transfected into EPCs, respectively. The cell morphology and the expressions of
      COL II and ACAN in each group were observed. RESULTS: Lentiviral transfection had
      no significant effect on the cell morphology. The EPCs were effectively
      transfected by the high expression Id1 lentivirus and RNAi Id1 lentivirus; the
      expression of Id1 mRNA was also significantly interfered. The expressions of COL
      II and ACAN mRNA and synthesis of COL II and ACAN protein were significantly
      higher in BMP-2 lentivirus and high expression Id1 lentivirus groups than control
      group (P < 0.05). The expression of COL II and ACAN protein were down regulated
      in the cartilage endplate cells when the expression of Id1 gene was decreased (P
      < 0.05). CONCLUSION: Up-regulation of Id1 gene expression can enhance the effects
      of BMP-2 on the synthesis of COL II and ACAN in EPCs.

PMID- 27044228
TI  - [OVER EXPRESSION OF Mash-1 GENE IN PROMOTING DIFFERENTIATION OF MOUSE EMBRYONIC
      STEM CELLS INTO NEURAL CELLS].
AB  - OBJECTIVE: To investigate the effects of over expression of Mash-1 gene on the
      differentiation of embryonic stem cells (ESC) into neural cells in vitro.
      METHODS: The ESC of rats (CE3 cells) were transfected with MSCV-Mash-1 (MSCV-Mash
      1-CE3 group) or MSCV (MSCV-CE3 group). The expression of Mash-1 gene was detected
      by RT-PCR. After transfection, hanging-drop culture was used to form embryonic
      bodies, and then embryonic bodies were cultured with neural induction medium. The
      cell morphology was observed under inverted phase contrast microscopy at 7 and 21
      days; the positive rates of neural stem cells marker protein (nestin) and neuron
      marker protein (beta-tubulin III) were measured by immunofluorescence staining
      after cell attachment; and the gene expressions of a-fetal protein (AFP),
      Brachyury, fibroblast growth factor 5 (FGF-5), Oct3/4, nestin, and beta-tubulin
      III were detected by real-time fluorescence quantitative PCR at 0, 1, 7, 14, and
      21 days after culture. The CE3 cells were used as control (CE3 group). RESULTS:
      Compared with MSCV-CE3 and CE3 groups, the expression of Mash-1 gene in MSCV-Mash
      1-CE3 group was significantly increased. At 7 and 21 days after neural induction
      cultured, cells in MSCV-Mash-1-CE3 group had axons growth and showed neural stem
      cell-like and neuron cell-like morphology (unipolar, bipolar, and multipolar
      neurons), but few cells had axons growth in MSCV-CE3 and CE3 groups. The positive
      rates of nestin at 7 days and beta-tubulin III at 21 days in MSCV-Mash-1-CE3
      group were significantly higher than those in MSCV-CE3 and CE3 groups (P < 0.05).
      Real-time fluorescence quatitative PCR results showed that the gene expression of
      Brachyury was significantly decreased after 1 day (P < 0.05), and the gene
      expressions of FGF-5 and nestin were significantly increased after 1 day (P <
      0.05) in MSC V-Mash- 1-CE3 group when compared with CE3 and MSCV-CE3 groups; the
      gene expression of beta-tubulin III was significantly increased after 7 days (P <
      0.05). There was no significant difference in above indexes between CE3 and MSCV
      CE3 groups (P > 0.05). The expressions of AFP and Oct3/4 showed no significant
      difference among groups at each time point (P>0.05). CONCLUSION: Over expression
      of Mash-1 gene can promote differentiation of ESC into neural cells in vitro.

PMID- 27044229
TI  - [RESEARCH ADVANCE OF DIFFERENTIATION OF INDUCED PLURIPOTENT STEM CELLS INTO
      Schwann CELLS IN VITRO].
AB  - OBJECTIVE: To review the research advance of differentiation of induced
      pluripotent stem cells (iPS) into Schwann cells in vitro in recent years.
      METHODS: Related literatures on differentiation of iPS into Schwann cells in
      vitro at present were consulted, the induction methods of iPS differentiating
      into Schwann cells in vitro were summarized, and the differentiated cells were
      identified and detected. RESULTS: The research results indicate that iPS can
      differentiate into Schwann cells. So far, the iPS have to differentiate into
      neural crest cells or neural crest stem cells firstly, and then differentiate
      into Schwann cells. S100-beta and glial fibrillary acidic protein (GFAP) are
      recognized as the marker of Schwann cells. The evidence of generating Schwann
      cells was that the neural crest cells or neural crest stem cells were labelled by
      p75+, HNK1+, or nestin+ before differentiation, and by S100-beta+ and GFAP+ after
      induction. CONCLUSION: Despite the increasing reported studies of Schwann cells
      from iPS, there have been few successful induction methods, so this field of
      cytology needs further study.

PMID- 27044230
TI  - [RESEARCH PROGRESS OF NEURAL REGULATION MECHANISM OF VASCULOGENESIS].
AB  - OBJECTIVE: To review the research progress of neural regulation mechanism of
      vasculogenesis. METHODS: The relevant literature on neural regulation mechanism
      of vasculogenesis was extensively reviewed. RESULTS: Neural regulation of
      vasculogenesis depends on synergistic effect among various cells of neurovascular
      unit, and co-participation of multiple cytokines, and it is closely related to a
      variety of repair mechanism, such as nerve regeneration and synaptic plasticity,
      but the specific mechanism need to be further investigated. CONCLUSION: The
      research of the neural regulation mechanism of vasculogenesis will contribute to
      further understanding repair mechanism of nerves and vessels injuries.

PMID- 27044231
TI  - The Five Stages of Grief: Coming to Terms With the New Sick Leave Regulations.

PMID- 27044232
TI  - Silver Diamine Fluoride: It's About Time!

PMID- 27044233
TI  - Kahe.

PMID- 27044234
TI  - Interprofessional Education and Practice...Dentistry in an Integrated Health Care
      System.

PMID- 27044235
TI  - Can Health Care Reform Connect Mouth and Body?

PMID- 27044236
TI  - Innovations in Oral Health Education and Practice.

PMID- 27044237
TI  - A Population Health Management Approach to Oral Health.
AB  - Clinical outcomes have been shown to be better, and total costs lower, when
      patients with chronic illness such as diabetes are managed using a population
      health strategy in a primary care setting that includes structured coordination
      of care with specialty services. This "population health management approach"
      offers a promising new vision for addressing oral disease as a chronic illness
      through a collaborative partnership between primary care teams and dental
      professionals.

PMID- 27044238
TI  - Permanente Dental Associates P.C.: Integrated Care Case Study.

PMID- 27044239
TI  - Marshfield Clinic Health System: Integrated Care Case Study.

PMID- 27044240
TI  - Health Partners of Western Ohio: Integrated Care Case Study.
AB  - Health centers are unique health care delivery organizations in which multiple
      disciplines, such as primary care, dental, behavioral health, pharmacy, podiatry,
      optometry and alternative medicine, are often located at the same site. Because
      of this characteristic, many health centers have developed systems of integrated
      care. This paper describes the characteristics of health centers and highlights
      the integrated health care delivery system of one early adopter health center,
      Health Partners of Western Ohio.

PMID- 27044241
TI  - Health Partners: Integrated Care Case Study.

PMID- 27044242
TI  - Taking Protected Health Information Precautions With Third Parties.

PMID- 27044243
TI  - Required Employee Training.

PMID- 27044244
TI  - A look into the latest dental and general technology on the market.

PMID- 27044245
TI  - Associations between non-traditional lipid measures and risk for type 2 diabetes
      mellitus in a Chinese community population: a cross-sectional study.
AB  - BACKGROUND: This study investigated associations between type 2 diabetes mellitus
      and non-traditional lipid measures (total cholesterol (TC)/high-density
      lipoprotein cholesterol (HDL-C), triglycerides (TG)/HDL-C, and non-HDL-C).
      METHODS: We conducted a community-based, cross-sectional study of 9 078
      participants aged 18 years or older (4 768 men and 4 310 women) who lived in the
      Jidong community, Tangshan, China. The adjusted odds ratios for type 2 diabetes
      were calculated for every standard deviation change in TC, log-transformed TG,
      HDL-C, LDL-C, non-HDL-C, TC/HDL-C, and log-transformed TG/HDL-C using
      multivariate logistic regression analysis. Receiver operating characteristic
      (ROC) curve analysis was used to define the points of maximum sum of sensitivity
      and specificity for each lipid measure as a predictor for type 2 diabetes.
      RESULTS: Prevalence of type 2 diabetes was 6.29%. Higher TC, TG, LDL-C, non-HDL
      C, TC/HDL-C, and TG/HDL-C, and lower HDL-C levels were individually associated
      with type 2 diabetes in multivariate analyses (all P < 0.05). TC/HDL-C was
      superior at discriminating between participants with and without type 2 diabetes
      compared with LDL-C (comparing ROC: P < 0.001), HDL-C (P < 0.001), TG (P =
      0.012), TC (P < 0.001), non-HDL-C (P = 0.001), and TG/HDL-C (P = 0.03). The
      cutoff point for TC/HDL-C was 1.30 mmol/L in this population from the Jidong
      community. Sensitivity and specificity values for TC/HDL-C were 0.77 and 0.53,
      respectively. CONCLUSIONS: TC/HDL-C is associated with type 2 diabetes and is
      superior to LDL-C and HDL-C as a risk marker in this population.

PMID- 27044246
TI  - Disagreeableness as a Cause and Consequence of Ostracism.
AB  - Ostracism's negative consequences have been widely documented, but research has
      yet to explore the personality characteristics of its targets that precipitate
      ostracism. Based on theories of the functions of ostracism, we found that people
      are more willing to ostracize disagreeable targets than more agreeable targets
      (Studies 2 and 3). This outcome was mediated by participants' interpersonal trust
      toward the target, and was especially strong for people who highly endorse
      fairness as a foundation for morality (Study 4). Ironically, the experience of
      ostracism induced a state of disagreeableness: the very characteristic that
      elicits ostracism from others (Study 5). This relationship was mediated by
      feelings of anger (Study 6). Findings indicate disagreeableness is a particularly
      negative outcome of ostracism, because it leads to further ostracism.

PMID- 27044247
TI  - MEASUREMENT OF INDOOR RADON-THORON IN AIR AND EXHALATION FROM SOIL IN THE
      ENVIRONMENT OF WESTERN HARYANA, INDIA.
AB  - Measurement of indoor radon and thoron is important because the inhalation of
      radon-thoron and their daughters contributes more than 50 % of the total dose
      from natural sources. One of the important parameters to find out the
      contribution of soil and building materials towards indoor radon is radon
      exhalation rates, which can be used for estimation of indoor radon levels. The
      indoor radon and thoron levels from the air and radon exhalation rates from soil
      samples collected from two districts (Hisar and Fatehabad) of Western Haryana are
      measured using pin-hole-based radon-thoron dosimeter and LR-115 solid-state
      nuclear track detector by canister technique. The results show that the indoor
      radon and thoron levels from Hisar district varied from 11 to 112 and 11 to 80 Bq
      m-3, while for Fatehabad district from 5 to 24 and 59 to 105 Bq m-3,
      respectively, in summer season. In winter season, indoor radon and thoron levels
      from Hisar district varied from 15 to 43 and 32 to 102 Bq m-3, while for
      Fatehabad district from 18 to 31 and 11 to 80 Bq m-3, respectively. The indoor
      radon levels of 95 % locations lie well below the limit recommended by
      International Commission of Radiation Protection, 2011. The radon mass exhalation
      rate varied from 6 to 56 mBq kg-1 h-1 The radon mass exhalation rates from the
      soil samples were lower than the worldwide average, i.e. 56 mBq kg-1 h-1 There
      exists a poor correlation between indoor radon and exhalation rates. More
      investigations of measurement of radionuclide contents from rock and stone of
      study area can improve the understanding.

PMID- 27044248
TI  - Debate: what is the best method to monitor surgical performance?
AB  - BACKGROUND: There is considerable recent interest in the monitoring of individual
      surgeon or hospital surgical outcomes. If one aggregates data over time and
      assesses performance with a funnel plot, then the detection of any process
      deterioration or improvement could be delayed. The variable life adjusted display
      (VLAD) is widely used for monitoring on a case-by-case basis, but we show that
      use of the risk-adjusted Bernoulli cumulative sum (RA-CUSUM) chart leads to much
      better performance. DISCUSSION: We use simulation to illustrate that the RA-CUSUM
      chart has better performance than the VLAD in detecting changes in the rates of
      adverse events. We recommend the RA-CUSUM approach over the VLAD approach for
      monitoring surgical performance. If the VLAD is used, we recommend running the RA
      CUSUM chart in the background to generate signals that the process performance
      has changed.

PMID- 27044249
TI  - The clinical and cost effectiveness of a Breathlessness Intervention Service for
      patients with advanced non-malignant disease and their informal carers: mixed
      findings of a mixed method randomised controlled trial.
AB  - BACKGROUND: Breathlessness is the most common and intrusive symptom of advanced
      non-malignant respiratory and cardiac conditions. The Breathlessness Intervention
      Service (BIS) is a multi-disciplinary complex intervention, theoretically
      underpinned by a palliative care approach, utilising evidence-based non
      pharmacological and pharmacological interventions to support patients with
      advanced disease in managing their breathlessness. Having published the
      effectiveness and cost effectiveness of BIS for patients with advanced cancer and
      their carers, we sought to establish its effectiveness, and cost effectiveness,
      in advanced non-malignant conditions. METHODS: This was a single-centre Phase III
      fast-track single-blind mixed method RCT of BIS versus standard care for
      breathless patients with non-malignant conditions and their carers. Randomisation
      was to one of two groups (randomly permuted blocks). Eighty-seven patients
      referred to BIS were randomised (intervention arm n = 44; control arm n = 43
      received BIS after four-week wait); 79 (91 %) completed to key outcome
      measurement. The primary outcome measure was 0-10 numeric rating scale for
      patient distress due to breathlessness at four weeks. Secondary outcome measures
      were Chronic Respiratory Questionnaire, Hospital Anxiety and Depression Scale,
      Client Service Receipt Inventory, EQ-5D and topic-guided interviews. RESULTS:
      Qualitative analyses showed the positive impact of BIS on patients with non
      malignant conditions and their carers; quantitative analyses showed a non
      significant greater reduction in the primary outcome ('distress due to
      breathlessness'), when compared to standard care, of -0.24 (95 % CI: -1.30,
      0.82). BIS resulted in extra mean costs of L799, reducing to L100 when outliers
      were excluded; neither difference was statistically significant. The quantitative
      findings contrasted with those previously reported for patients with cancer and
      their carers, which showed BIS to be both clinically and cost effective. For
      patients with non-malignant conditions there was a notable trend of improvement
      over both trial arms to the key measurement point; participants may have
      experienced a therapeutic effect from the research interviews, diluting the
      intervention's impact. CONCLUSIONS: BIS had a statistically non-significant
      effect for patients with non-malignant conditions, and slightly increased service
      costs, but had a qualitatively positive impact consistent with findings for
      advanced cancer. Trials of palliative care interventions should consider
      multiple, mixed method, primary outcomes and ensure that protocols limit
      potential contaminating therapeutic effects in study designs. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN04119516 (December 2008); ClinicalTrials.gov
      NCT00678405 (May 2008).

PMID- 27044250
TI  - Galectin 3 acts as an enhancer of survival responses in H. pylori-infected
      gastric cancer cells.
AB  - Galectin 3 (Gal-3) is upregulated in gastric epithelial cells as a host response
      to Helicobacter pylori infection. However, the significance of Gal-3 expression
      in H. pylori-infected cells is not well established. We analyzed Gal-3
      intracellular expression, localization, and its effects in H. pylori-infected
      gastric epithelial cells. The predominantly nuclear confined Gal-3 was shown to
      be upregulated and exported out to the cytoplasm in H. pylori-infected AGS cells.
      The nuclear export was channeled through CRM-1 (exportin-1) protein.
      Interestingly, knock down of Gal-3 expression led to reduced NF-kappaB promoter
      activity and interleukin-8 (IL-8) secretion, suggesting its pro-inflammatory
      roles. Furthermore, Gal-3 was found to be pro-proliferative and anti-apoptotic in
      nature, as its knock down caused a reduction in cell proliferation and an
      increase in apoptosis, respectively. Taken together, our data suggest the
      expression and upregulation of Gal-3 as a critical endogenous event in H. pylori
      infection that interferes with various intracellular events, causing prolonged
      cell survival, which is characteristic in carcinogenesis. 

PMID- 27044251
TI  - Exploring tomato Solanum pennellii introgression lines for residual biomass and
      enzymatic digestibility traits.
AB  - BACKGROUND: Residual biomass production for fuel conversion represents a unique
      opportunity to avoid concerns about compromising food supply by using dedicated
      feedstock crops. Developing tomato varieties suitable for both food consumption
      and fuel conversion requires the establishment of new selection methods. RESULTS:
      A tomato Solanum pennellii introgression population was assessed for fruit yield,
      biomass phenotypic diversity, and for saccharification potential. Introgression
      lines 2-5, 2-6, 6-3, 7-2, 10-2 and 12-4 showed the best combination of fruit and
      residual biomass production. Lignin, cellulose, hemicellulose content and
      saccharification rate showed a wide variation in the tested lines. Within
      hemicellulose, xylose value was high in IL 6-3, IL 7-2 and IL 6-2, whereas
      arabinose showed a low content in IL 10-2, IL 6-3 and IL 2-6. The latter line
      showed also the highest ethanol potential production. Alkali pre-treatment
      resulted in the highest values of saccharification in most of lines tested,
      suggesting that chemical pretreatment is an important factor for improving
      biomass processability. Interestingly, extreme genotypes for more than one single
      trait were found, allowing the identification of better genotypes. Cell wall
      related genes mapping in genomic regions involved into tomato biomass production
      and digestibility variation highlighted potential candidate genes. Molecular
      expression profile of few of them provided useful information about challenged
      pathways. CONCLUSIONS: The screening of S. pennellii introgression population
      resulted very useful for delving into complex traits such as biomass production
      and digestibility. The extreme genotypes identified could be fruitfully employed
      for both genetic studies and breeding.

PMID- 27044252
TI  - Benchmarking trial between France and Australia comparing management of primary
      rectal cancer beyond TME and locally recurrent rectal cancer (PelviCare Trial):
      rationale and design.
AB  - BACKGROUND: Among patients with rectal cancer, 5-10% have a primary rectal cancer
      beyond the total mesorectal excision plane (PRC-bTME) and 10% recur locally
      following primary surgery (LRRC). In both cases, patients 'care remains
      challenging with a significant worldwide variation in practice regarding overall
      management and criteria for operative intervention. These variations in practice
      can be explained by structural and organizational differences, as well as
      cultural dissimilarities. However, surgical resection of PRC-bTME and LRRC
      provides the best chance of long-term survival after complete resection (R0).
      With regards to the organization of the healthcare system and the operative
      criteria for these patients, France and Australia seem to be highly different. A
      benchmarking-type analysis between French and Australian clinical practice, with
      regards to the care and management of PRC-bTME and LRRC, would allow
      understanding of patients' care and management structures as well as individual
      and collective mechanisms of operative decision-making in order to ensure
      equitable practice and improve survival for these patients. METHODS/DESIGN: The
      current study is an international Benchmarking trial comparing two cohorts of 120
      consecutive patients with non-metastatic PRC-bTME and LRRC. Patients with
      curative and palliative treatment intent are included. The study design has three
      main parts: (1) French and Australian cohorts including clinical, radiological
      and surgical data, quality of life (MOS SF36, FACT-C) and distress level
      (Distress thermometer) at the inclusion, 6 and 12 months; (2) experimental
      analyses consisting of a blinded inter-country reading of pelvic MRI to assess
      operatory decisions; (3) qualitative analyses based on MDT meeting observation,
      semi-structured interviews and focus groups of health professional attendees and
      conducted by a research psychologist in both countries using the same guides. The
      primary endpoint will be the clinical resection rate. Secondary end points will
      be concordance rate between French and Australian operative decisions based on
      the inter-country reading MRI, post-operative mortality and morbidity rates,
      oncological outcomes based on resection status and one-year overall and disease
      free survival, patients' quality of life and distress level. Qualitative analysis
      will compare obstacles and facilitators of operative decision-making between both
      countries. DISCUSSION: Benchmarking can be defined as a comparison and learning
      process which will allow, in the context of PRC-bTME and LRRC, to understand and
      to share the whole process management of these patientsbetween Farnce and
      Australia. TRIAL REGISTRATION: NCT02551471 . (date of registration: 09/14/2015).

PMID- 27044253
TI  - Evaluation of serological cross-reactivity and cross-neutralization between the
      United States porcine epidemic diarrhea virus prototype and S-INDEL-variant
      strains.
AB  - BACKGROUND: At least two genetically different porcine epidemic diarrhea virus
      (PEDV) strains have been identified in the United States (U.S. PEDV prototype and
      S-INDEL-variant strains). The current serological assays offered at veterinary
      diagnostic laboratories for detection of PEDV-specific antibody are based on the
      U.S. PEDV prototype strain. The objectives of this study were: 1) isolate the
      U.S. PEDV S-INDEL-variant strain in cell culture; 2) generate antisera against
      the U.S. PEDV prototype and S-INDEL-variant strains by experimentally infecting
      weaned pigs; 3) determine if the various PEDV serological assays could detect
      antibodies against the U.S. PEDV S-INDEL-variant strain and vice versa. RESULTS:
      A U.S. PEDV S-INDEL-variant strain was isolated in cell culture in this study.
      Three groups of PEDV-negative, 3-week-old pigs (five pigs per group) were
      inoculated orally with a U.S. PEDV prototype isolate (previously isolated in our
      lab), an S-INDEL-variant isolate or virus-negative culture medium. Serum samples
      collected at 0, 7, 14, 21 and 28 days post inoculation were evaluated by the
      following PEDV serological assays: 1) indirect fluorescent antibody (IFA) assays
      using the prototype and S-INDEL-variant strains as indicator viruses; 2) virus
      neutralization (VN) tests against the prototype and S-INDEL-variant viruses; 3)
      PEDV prototype strain whole virus based ELISA; 4) PEDV prototype strain S1-based
      ELISA; and 5) PEDV S-INDEL-variant strain S1-based ELISA. The positive antisera
      against the prototype strain reacted to and neutralized both prototype and S
      INDEL-variant viruses, and the positive antisera against the S-INDEL-variant
      strain also reacted to and neutralized both prototype and S-INDEL-variant
      viruses, as examined by IFA antibody assays and VN tests. Antibodies against the
      two PEDV strains could be detected by all three ELISAs although detection rates
      varied to some degree. CONCLUSIONS: These data indicate that the antibodies
      against U.S. PEDV prototype and S-INDEL-variant strains cross-reacted and cross
      neutralized both strains in vitro. The current serological assays based on U.S.
      PEDV prototype strain can detect antibodies against both U.S. PEDV strains.

PMID- 27044254
TI  - Timely identification of palliative patients and anticipatory care planning by
      GPs: practical application of tools and a training programme.
AB  - BACKGROUND: Palliative care is mainly restricted to terminal care. General
      practitioners (GPs) are not trained to early identify palliative patients with
      cancer, COPD or heart failure. With the help of the RADboud indicators for
      PAlliative Care needs (RADPAC), we trained GPs to identify patients' needs and to
      make a proactive care plan. They were also able to join two role-plays where they
      discussed the patient's future, and consulted a palliative care consultant to
      fine-tune the care plan. We evaluated the programme with the GPs and consultants
      and noted its impact on their daily practice. METHODS: Two years after they had
      participated in the programme, we held semi-structured interviews with the GPs
      and a focus group interview with the consultants and performed a thematic content
      analysis. RESULTS: Six consultants and nine GPs participated in the programme.
      Most GPs and consultants mentioned positive changes in the thinking or acting of
      GPs regarding early palliative care. A number continued to use the tool to
      identify patients; most of the others noted they had internalised the indicators.
      Although half of them still considered discussing end-of-life aspects difficult,
      particularly in patients with organ failure, the others were more easily able to
      discuss the future with their palliative patients. CONCLUSION: Although most GPs
      and consultants were positive about the training programme and applying it in
      daily practice, we conclude that in future programmes, more attention needs to
      paid to timely identification of palliative patients with COPD or CHF and how to
      discuss the future with them.

PMID- 27044255
TI  - Erratum to: Phosphotriesterase-related protein sensed albuminuria and conferred
      renal tubular cell activation in membranous nephropathy.

PMID- 27044256
TI  - Transcriptomics resources of human tissues and organs.
AB  - Quantifying the differential expression of genes in various human organs,
      tissues, and cell types is vital to understand human physiology and disease.
      Recently, several large-scale transcriptomics studies have analyzed the
      expression of protein-coding genes across tissues. These datasets provide a
      framework for defining the molecular constituents of the human body as well as
      for generating comprehensive lists of proteins expressed across tissues or in a
      tissue-restricted manner. Here, we review publicly available human transcriptome
      resources and discuss body-wide data from independent genome-wide transcriptome
      analyses of different tissues. Gene expression measurements from these
      independent datasets, generated using samples from fresh frozen surgical
      specimens and postmortem tissues, are consistent. Overall, the different genome
      wide analyses support a distribution in which many proteins are found in all
      tissues and relatively few in a tissue-restricted manner. Moreover, we discuss
      the applications of publicly available omics data for building genome-scale
      metabolic models, used for analyzing cell and tissue functions both in
      physiological and in disease contexts. 

PMID- 27044257
TI  - End-of-life decisions in acute stroke patients: an observational cohort study.
AB  - BACKGROUND: Crucial issues of modern stroke care include best practice end-of
      life-decision (EOLD)-making procedures and the provision of high-quality
      palliative care for dying stroke patients. METHODS: We retrospectively analyzed
      records of those patients who died over a 4-year period (2011-2014) on our Stroke
      Unit concerning EOLD, focusing on the factors that most probably guided decisions
      to induce limitation of life-sustaining therapy and subsequently end-of-life-care
      procedures thereafter. RESULTS: Of all patients treated at our Stroke Unit, 120
      (2.71%) died. In 101 (86.3%), a do-not-resuscitate-order (DNRO) was made during
      early treatment. A decision to withdraw/withhold further life supportive therapy
      was made in 40 patients (34.2%) after a mean of 5.0 days (range 0-29). Overall
      patient death occurred after a mean time of 7.0 days (range 1-30) and 2.6 days
      after therapy restrictions. Disturbance of consciousness at presentation,
      dysphagia on day 1 and large supratentorial stroke were possible indicators of
      decisions to therapeutic withdrawing/withholding. Proceedings of EOL care in
      these patients were heterogeneous; in most cases monitoring (95%), medical
      procedures (90%), oral medication (88%), parenteral nutrition (98%) and
      antibiotic therapy (86%) were either not ordered or withdrawn, however IV fluids
      were continued in all patients. CONCLUSIONS: A high percentage of stroke patients
      were rated as terminally ill and died in the course of caregiving. Disturbance of
      consciousness at presentation, dysphagia on day 1 and large supratentorial stroke
      facilitated decisions to change therapeutic goals thus initiating end-of-life
      care. However, there is further need to foster research on this field in order to
      ameliorate outcome prognostication, to understand the dynamics of EOLD-making
      procedures and to educate staff to provide high-quality patient-centred
      palliative care in stroke medicine.

PMID- 27044258
TI  - Cellular localization of guanylin and uroguanylin mRNAs in human and rat duodenal
      and colonic mucosa.
AB  - Guanylin (GUCA2A/Guca2a/GN) and uroguanylin (GUCA2B/Guca2b/UGN) are expressed in
      the gastrointestinal tract and have been implicated in ion and fluid homeostasis,
      satiety, abdominal pain, growth and intestinal barrier integrity. Their cellular
      sources are debated and include goblet cells, entero-/colonocytes,
      enteroendocrine (EE) cells and tuft cells. We therefore investigated the cellular
      sources of GN and UGN mRNAs in human and rat duodenal and colonic epithelium with
      in situ hybridization (ISH) to determine co-expression with Chromogranin A
      (CHGA/Chga/CgA; enterochromaffin [EC] cells), defensin alpha 6 (DEFA6/Defa6;
      Paneth cells), mucin 2 (MUC2/Muc2; goblet cells) and selected tuft cell markers.
      GUCA2A/Guca2a expression was localized to goblet cells and colonocytes in human
      and rat colon. In human duodenum, GUCA2A was expressed in Paneth cells and was
      scarce in villous epithelial cells. In rat duodenum, Guca2a was only localized to
      goblet cells. Guca2b was focally expressed in rat colon. In human and rat
      duodenum and in human colon, GUCA2B/Guca2b was expressed in dispersed solitary
      epithelial cells, some with a tuft cell-like appearance. Neither GUCA2A nor
      GUCA2B were co-expressed with CHGA in human duodenal cells. Consequently, EC
      cells are probably not the major source of human GN or UGN but other EE cells as
      a source of GN or UGN are not entirely excluded. No convincing overlap with tuft
      cell markers was found. For the first time, we demonstrate the cellular
      expression of GUCA2B in human duodenum. The specific cellular distribution of
      both GN and UGN differs between duodenum and colon and between human and rat
      intestines.

PMID- 27044259
TI  - Dilemma of managing asymptomatic children referred with 'culture-confirmed' drug
      resistant tuberculosis.
AB  - BACKGROUND: The diagnosis of drug-resistant tuberculosis (DR-TB) in children is
      challenging and treatment is associated with many adverse effects. OBJECTIVE: We
      aimed to assess if careful observation, without initiation of second-line
      treatment, is safe in asymptomatic children referred with 'culture-confirmed' DR
      TB. SETTING: KwaZulu-Natal, South Africa-an area with high burdens of HIV, TB and
      DR-TB. DESIGN, INTERVENTION AND MAIN OUTCOME MEASURES: We performed an outcome
      review of children with 'culture-confirmed' DR-TB who were not initiated on
      second-line TB treatment, as they were asymptomatic with normal chest radiographs
      on examination at our specialist referral hospital. Children were followed up
      every other month for the first year, with a final outcome assessment at the end
      of the study. RESULTS: In total, 43 asymptomatic children with normal chest
      radiographs were reviewed. The median length of follow-up until final evaluation
      was 549 days (IQR 259-722 days); most (34; 83%) children were HIV uninfected.
      Resistance patterns included 9 (21%) monoresistant and 34 (79%) multidrug
      resistant (MDR) strains. Fifteen children (35%) had been treated with first-line
      TB treatment, prior to presentation at our referral hospital. At the final
      evaluation, 34 (80%) children were well, 7 (16%) were lost to follow-up, 1 (2%)
      received MDR-TB treatment and 1 (2%) died of unknown causes. The child who
      received MDR-TB treatment developed new symptoms at the 12-month review and
      responded well to second-line treatment. CONCLUSIONS: Bacteriological evaluation
      should not be performed in the absence of any clinical indication. If drug
      resistant Mycobacterium tuberculosis is detected in an asymptomatic child with a
      normal chest radiograph, close observation may be an appropriate strategy,
      especially in settings where potential laboratory error and poor record keeping
      are constant challenges.

PMID- 27044260
TI  - A congenital localised reticular vascular malformation.

PMID- 27044261
TI  - AZD9291 overcomes T790 M-mediated resistance through degradation of
      EGFR(L858R/T790M) in non-small cell lung cancer cells.
AB  - The discovery of activating mutations of epidermal growth factor receptor (EGFR)
      has resulted in the development of more effective treatments for non-small cell
      lung cancer (NSCLC). Although first-generation EGFR tyrosine kinase inhibitors
      (EGFR TKIs) provide significant clinical benefit, acquired resistance often
      occurs, most commonly (>50 %) via a T790 M resistance mutation. Although AZD9291
      is selective for both T790 M and activating EGFR mutations over wild-type EGFR,
      it is highly active when T790 M is present, especially EGFR(L858R/T790M), and
      modestly active when T790 M is absent. The aim of this study was to elucidate the
      underlying mechanism of the high sensitivity of NSCLC cells harboring
      EGFR(L858R/T790M) to AZD9291. In H1975 cells harboring EGFR(L858R/T790M), AZD9291
      potently inhibited cellular growth and EGFR signaling pathways together with
      depletion of mutant EGFR protein. AZD9291-induced depletion of EGFR(L858R/T790M)
      protein was abrogated through inhibition of the proteasome with MG132. However,
      AZD9291 had no effect on protein levels of EGFR(WT) and EGFR(L858R). In addition,
      AZD9291 induced apoptosis and caused expression changes in cell cycle-related
      genes. Moreover, oral administration of AZD9291 as a single agent induced tumor
      regression in vivo in a H1975 tumor xenograft model and reduced EGFR(L858R/T790M)
      protein levels in xenograft tumors. Taken together, our results provide a
      potential mechanism for the sensitivity of EGFR(L858R/T790M) cells to AZD9291 and
      suggest that AZD9291 may be effective in cases of T790 M-positive EGFR
      resistance.

PMID- 27044262
TI  - Human lung fibroblasts may modulate dendritic cell phenotype and function:
      results from a pilot in vitro study.
AB  - In human lung fibrotic lesions, fibroblasts were shown to be closely associated
      with immature dendritic cell (DC) accumulation. The aim of the present pilot
      study was to characterize the role of pulmonary fibroblasts on DC phenotype and
      function, using co-culture of lung fibroblasts from patients with idiopathic
      pulmonary fibrosis (IPF) and from control patients, with a DC cell line MUTZ-3.
      We observed that co-culture of lung control and IPF fibroblasts with DCs reduced
      the expression of specific DC markers and down-regulated their T-cell stimulatory
      activity. This suggests that pulmonary fibroblasts might sustain chronic
      inflammation in the fibrotic lung by maintaining in situ a pool of immature DCs. 

PMID- 27044263
TI  - In vitro and in vivo activity of melflufen (J1)in lymphoma.
AB  - BACKGROUND: Melphalan has been used in the treatment of various hematologic
      malignancies for almost 60 years. Today it is part of standard therapy for
      multiple myeloma and also as part of myeloablative regimens in association with
      autologous allogenic stem cell transplantation. Melflufen (melphalan flufenamide
      ethyl ester, previously called J1) is an optimized derivative of melphalan
      providing targeted delivery of active metabolites to cells expressing
      aminopeptidases. The activity of melflufen has compared favorably with that of
      melphalan in a series of in vitro and in vivo experiments performed
      preferentially on different solid tumor models and multiple myeloma. Melflufen is
      currently being evaluated in a clinical phase I/II trial in relapsed or relapsed
      and refractory multiple myeloma. METHODS: Cytotoxicity of melflufen was assayed
      in lymphoma cell lines and in primary tumor cells with the Fluorometric
      Microculture Cytotoxicity Assay and cell cycle analyses was performed in two of
      the cell lines. Melflufen was also investigated in a xenograft model with
      subcutaneous lymphoma cells inoculated in mice. RESULTS: Melflufen showed
      activity with cytotoxic IC50-values in the submicromolar range (0.011-0.92 MUM)
      in the cell lines, corresponding to a mean of 49-fold superiority (p < 0.001) in
      potency vs. melphalan. In the primary cultures melflufen yielded slightly lower
      IC50-values (2.7 nM to 0.55 MUM) and an increased ratio vs. melphalan (range 13
      455, average 108, p < 0.001). Treated cell lines exhibited a clear accumulation
      in the G2/M-phase of the cell cycle. Melflufen also showed significant activity
      and no, or minimal side effects in the xenografted animals. CONCLUSION: This
      study confirms previous reports of a targeting related potency superiority of
      melflufen compared to that of melphalan. Melflufen was active in cell lines and
      primary cultures of lymphoma cells, as well as in a xenograft model in mice and
      appears to be a candidate for further evaluation in the treatment of this group
      of malignant diseases.

PMID- 27044265
TI  - GP practices face CQC fee hikes of L2000 a year.

PMID- 27044264
TI  - Effectiveness of training in evidence-based medicine skills for healthcare
      professionals: a systematic review.
AB  - BACKGROUND: Basic skills in evidence-based medicine (EbM) are indispensable for
      healthcare professionals to promote consumer-centred, evidence-based treatment.
      EbM training courses are complex interventions - a fact that has not been
      methodologically reflected by previous systematic reviews. This review evaluates
      the effects of EbM training for healthcare professionals as well as the quality
      of reporting of such training interventions. METHODS: We searched PubMed, EMBASE,
      CINAHL, Cochrane Library, ERIC, Campbell Library and PsycINFO up to 9/2014.
      Randomised controlled trials, controlled clinical trials as well as before-after
      trials were included. Authors were contacted in order to obtain missing data. Two
      independent reviewers extracted data and assessed risk of bias. RESULTS: We
      reviewed 14.507 articles; n = 61 appeared potentially eligible; n = 13 involving
      1,120 participants were included. EbM training shows some impact on knowledge and
      skills, whereas the impact on practical EbM application remains unclear. Risk of
      bias of included trials raises uncertainty about the effects. Description of
      complex interventions was poor. CONCLUSIONS: EbM training has some positive
      effects on knowledge and skills of healthcare professionals. Appropriate methods
      for development, piloting, evaluation, reporting and implementation of the
      training should be applied.

PMID- 27044266
TI  - Prognosis of ocular syphilis in patients infected with HIV in the antiretroviral
      therapy era.
AB  - OBJECTIVE: To describe the clinical course and prognosis of ocular syphilis in
      patients infected with HIV-1 in the antiretroviral therapy (ART) era. METHODS: We
      conducted a single-centre retrospective chart review of ocular syphilis in
      patients infected with HIV-1 diagnosed between August 1997 and July 2015. The
      prognosis of best-corrected visual acuity (BCVA) was analysed. RESULTS: The study
      subjects were 30 eyes of 20 men who had sex with men (MSM) (median age, 41). Loss
      of vision and posterior uveitis were the most common ocular clinical features
      (43%) and location of inflammation at presentation (50%), respectively. The
      median baseline BCVA was 0.4 (IQR 0.2-1.2), including three eyes with hand
      motion. BCVA<=0.4 at diagnosis was significantly associated with posterior
      uveitis or panuveitis (p=0.044). Seventy-five per cent were treated with
      intravenous benzylpenicillin and 53% were diagnosed with neurosyphilis. After
      treatment (median follow-up: 21 months), BCVA improved in 89% of the eyes,
      including all eyes with hand motion, to a median BCVA of 1.2 (IQR 0.8-1.2).
      Kaplan-Meier analysis showed that >28 days of ocular symptoms before diagnosis
      was the only factor associated with poor prognosis of BCVA. Three patients (15%)
      developed recurrence after treatment. CONCLUSIONS: The prognosis of BCVA in HIV
      infected patients with ocular syphilis in the ART era was favourable after proper
      treatment. Having >28 days of ocular symptoms before diagnosis was associated
      with poor prognosis. Changes in visual acuity in HIV-infected MSM should prompt
      an immediate assessment for ocular syphilis as delays in diagnosis and therapy
      can lead to irreversible visual loss.

PMID- 27044267
TI  - High hepatitis C virus (HCV) prevalence among men who have sex with men (MSM) in
      Vietnam and associated risk factors: 2010 Vietnam Integrated Behavioural and
      Biologic Cross-Sectional Survey.
AB  - BACKGROUND: Hepatitis C virus (HCV) is an increasing health issue among key
      populations such as men who have sex with men (MSM). We sought to assess the
      burden of and risk factors for HCV among MSM in Vietnam. METHODS: We analysed
      behavioural and demographic data and stored specimens from MSM surveyed in four
      provinces through Vietnam's 2009-2010 Integrated Biologic and Behavioural Survey,
      which used probability-based, respondent-driven sampling. Commercial hepatitis B
      surface antigen (HBsAg) and HCV/antibody (HCV Ag/Ab) testing were performed on
      archived sera with follow-up PCR for HCV RNA and genotype determination. RESULTS:
      Among the 1588 MSM surveyed, the median (range) frequency, by province, of HCV
      Ag/Ab detection was 28.4% (13.7%-38.8%); 84.5% (83.1%-100%) among HIV-infected
      and 21.9% (8.9%-28.2%) among HIV-uninfected. HCV prevalence was higher in
      northern Hanoi and Hai Phong provinces than in southern Ho Chi Minh City and Chan
      Tho provinces. Among a convenience sample of 67 HCV Ag/Ab+ MSM, 67.2% were HCV
      RNA+; of 41 genotyped, 73.2% were genotype 1. HBsAg prevalence varied from 8.5%
      to 27.4%. In the multivariable logistic regression analysis, being HIV-infected
      (adjusted OR (aOR) 19.0; 7.0-51.9), ever having used injected drugs (aOR 4.4; 1.6
      12.4) and age >25 years were significant risk factors for testing HCV Ag/Ab+.
      CONCLUSIONS: HCV infection in Vietnam appears to be high among MSM, particularly
      among HIV-infected MSM, with a north-south gradient. Given overlapping risk
      behaviours and associations between HCV and HIV, integrating HIV and HCV
      programme services to prevent both HIV and HCV transmission among MSM is
      indicated.

PMID- 27044268
TI  - To be or not to be a facilitator of reflective learning for medical students? a
      case study of medical teachers' perceptions of introducing a reflective writing
      exercise to an undergraduate curriculum.
AB  - BACKGROUND: Introducing reflective writing to a medical curriculum requires the
      acceptance and participation of teachers. The purpose of this study was to
      explore medical teachers' views on the benefits of introducing a reflective
      writing exercise into an undergraduate medical curriculum, including their levels
      of satisfaction and their concerns. We also investigated effects on the teachers'
      personal and professional development arising from their roles as novice
      facilitators. METHODS: A qualitative approach was employed using semi-structured
      interviews. During an attachment to Primary Care Medicine course, fourth-year
      medical students (n = 180) in the Faculty of Medicine, Ramathibodi Hospital,
      Bangkok, Thailand were assigned to write a reflective essay titled, "A
      Significant Event in My First Clinical Year". After reading the essays and
      facilitating between one to three small group discussions based on these, each of
      the 18 teachers enrolled in our study completed an in-depth face to face
      interview. Transcripts of these were studied, using thematic content analysis to
      identify emerging themes. RESULTS: The novice facilitators felt that facilitated
      reflection was both valuable and appropriate for students. They also perceived
      that it had a positive impact on their own personal and professional lives. In
      the early phase of implementing this activity, teachers expressed concerns about
      1) their ability and confidence as facilitators in small group discussion 2)
      their ability to deal with emotions raised within their groups 3) the
      effectiveness of the activity 4) poor presentation and possible fabrication of
      student work. CONCLUSIONS: Most teachers regarded this activity as being
      beneficial to them, to student learning, and to the curriculum. Their insights,
      including concerns about the level of skill needed for facilitation, provide
      valuable material for planning a comprehensive faculty development programme.

PMID- 27044269
TI  - Renal Stent Crushed During Open Aneurysmorrhaphy for Endoleak After Fenestrated
      EVAR.
AB  - PURPOSE: To report a complication of renal stent crushing during open
      aneurysmorrhaphy performed 10 years after fenestrated endovascular aneurysm
      repair (FEVAR). CASE REPORT: A 67-year-old male patient underwent elective FEVAR
      of a juxtarenal aortic aneurysm. Uncovered balloon-expandable stents were placed
      through the fenestrations for the superior mesenteric and right renal arteries;
      the left renal artery received a Jostent covered balloon-expandable stent. The
      uncovered right renal stent was noted to be crushed on the first imaging after
      FEVAR, but was left untreated; the right kidney was thereafter significantly
      smaller than the left. Over several years, the aneurysm expanded, and type II
      endoleak involving the lumbar arteries was embolized with coils 7 years after
      FEVAR. Despite this, the aneurysm continued to enlarge and reached a diameter of
      12.8 cm. Open aneurysmorrhaphy and selective ligation of lumbar arteries was
      performed 10 years after FEVAR. The first surveillance imaging after
      aneurysmorrhaphy demonstrated a new finding of a crushed left renal stent, which
      was presumed to be related to surgical instrumentation. The stent was
      successfully redilated percutaneously, and renal function remained stable.
      Computed tomography demonstrated a normal appearance of the left renal covered
      stent after re-expansion. Doppler ultrasound after 7.5 months showed normal renal
      perfusion. CONCLUSION: Balloon-expandable visceral artery stents are susceptible
      to crush injury during aortic surgery. Consideration should be given to early
      imaging after such surgery in FEVAR patients.

PMID- 27044270
TI  - Intravascular Ultrasound-Derived Stent Dimensions as Predictors of Angiographic
      Restenosis Following Nitinol Stent Implantation in the Superficial Femoral
      Artery.
AB  - PURPOSE: To identify intravascular ultrasound (IVUS) measurements that can
      predict angiographic in-stent restenosis (ISR) following nitinol stent
      implantation in superficial femoral artery (SFA) lesions. METHODS: A
      retrospective review was conducted of 97 patients (mean age 72.9+/-8.9 years; 63
      men) who underwent IVUS examination during endovascular treatment of 112 de novo
      SFA lesions between July 2012 and December 2014. Self-expanding bare stents were
      implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months
      after stenting, follow-up angiography was conducted to assess stent patency. The
      primary endpoint was angiographic ISR determined by quantitative vascular
      angiography analysis at the 6-month follow-up. Variables associated with
      restenosis were sought in multivariate analysis; the results are presented as the
      odds ratio (OR) and 95% confidence interval (CI). RESULTS: At follow-up, 27
      (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated
      stents were more prevalent in the ISR group compared with the no restenosis group
      (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4+/-79.5 vs 109.0+/-89.3
      mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was
      smaller (13.9+/-2.8 vs 16.3+/-1.6 mm(2), p<0.001) in the ISR group. Multivariate
      analysis revealed that bare stent use (OR 7.11, 95% CI 1.70 to 29.80, p<0.01) and
      longer lesion length (OR 1.08, 95% CI 1.01 to 1.16, p=0.04) were predictors of
      ISR, while increasing postprocedure MSA (OR 0.58, 95% CI 0.41 to 0.82, p<0.01)
      was associated with lower risk of ISR. Receiver operating characteristic analysis
      identified a MSA of 15.5 mm(2) as the optimal cutpoint below which the incidence
      of restenosis increased (area under the curve 0.769). CONCLUSION: Postprocedure
      MSA can predict ISR in SFA lesions, which suggests that adequate stent
      enlargement during angioplasty might be required for superior patency.

PMID- 27044271
TI  - A Rescue Technique for Intraoperative Proximal Migration of a Nellix Stent During
      Endovascular Aneurysm Sealing.
AB  - PURPOSE: To describe a technique to rescue intraoperative migration of 1 of the 2
      Nellix stents during endovascular sealing of abdominal aortic aneurysms (EVAS).
      TECHNIQUE: The technique requires advancement and inflation of a 10-mm
      angioplasty balloon into the inlet of the migrated stent via an upper limb
      approach. Inflation of the balloon allows completion of EVAS without risking the
      contralateral endobag occluding the inlet of the migrated stent. CONCLUSION: This
      technique allows safe completion of EVAS without compromising stent patency or
      aneurysm seal and should be considered when intraoperative migration of a Nellix
      stent occurs despite appropriate precautions.

PMID- 27044272
TI  - Study protocol for the Flooring for Injury Prevention (FLIP) Study: a randomised
      controlled trial in long-term care.
AB  - BACKGROUND: A promising strategy for reducing the incidence and severity of fall
      related injuries in long-term care (LTC) is to decrease the ground surface
      stiffness, and the subsequent forces applied to the body parts at impact, through
      installation of compliant flooring that does not substantially affect balance or
      mobility. Definitive evidence of the effects of compliant flooring on fall
      related injuries in LTC is lacking. The Flooring for Injury Prevention (FLIP)
      Study is designed to address this gap. METHODS: The FLIP Study is a 4-year,
      parallel-group, 2-arm, randomised controlled superiority trial of flooring in 150
      resident rooms at a LTC site. The primary objective is to determine whether
      compliant flooring reduces serious fall-related injuries relative to control
      flooring. Intervention (2.54 cm SmartCells compliant; 74 rooms) and control (2.54
      cm plywood; 76 rooms) floorings were installed over the top of existing concrete
      floors and covered with identical 2.00 mm vinyl. The primary outcome is serious
      fall-related injury, defined as any impact-related injury due to a fall in a
      study room that results in Emergency Department visit or hospital admission.
      Secondary outcomes include minor fall-related injury, any fall-related injury,
      falls, number of fallers, fractures, and healthcare utilisation and costs for
      serious fall-related injuries. Randomisation of study rooms, and residents in
      rooms, was stratified by residential unit, and flooring assignments were
      concealed. Outcome ascertainment began September 2013. DISCUSSION: Results from
      the FLIP Study will provide evidence about the effects of compliant flooring on
      fall-related injuries in LTC and will guide development of safer environments for
      vulnerable older adults. TRIAL REGISTRATION NUMBER: NCT01618786.

PMID- 27044273
TI  - Combining statistics from two national complex surveys to estimate injury rates
      per hour exposed and variance by activity in the USA.
AB  - BACKGROUND: A common issue in descriptive injury epidemiology is that in order to
      calculate injury rates that account for the time spent in an activity, both
      injury cases and exposure time of specific activities need to be collected. In
      reality, few national surveys have this capacity. To address this issue, we
      combined statistics from two different national complex surveys as inputs for the
      numerator and denominator to estimate injury rate, accounting for the time spent
      in specific activities and included a procedure to estimate variance using the
      combined surveys. METHODS: The 2010 National Health Interview Survey (NHIS) was
      used to quantify injuries, and the 2010 American Time Use Survey (ATUS) was used
      to quantify time of exposure to specific activities. The injury rate was
      estimated by dividing the average number of injuries (from NHIS) by average
      exposure hours (from ATUS), both measured for specific activities. The variance
      was calculated using the 'delta method', a general method for variance estimation
      with complex surveys. RESULTS: Among the five types of injuries examined, 'sport
      and exercise' had the highest rate (12.64 injuries per 100 000 h), followed by
      'working around house/yard' (6.14), driving/riding a motor vehicle (2.98),
      working (1.45) and sleeping/resting/eating/drinking (0.23). The results show a
      ranking of injury rate by activity quite different from estimates using
      population as the denominator. CONCLUSIONS: Our approach produces an estimate of
      injury risk which includes activity exposure time and may more reliably reflect
      the underlying injury risks, offering an alternative method for injury
      surveillance and research.

PMID- 27044274
TI  - Towards understanding temporal and spatial dynamics of Bactrocera oleae (Rossi)
      infestations using decade-long agrometeorological time series.
AB  - Insect dynamics depend on temperature patterns, and therefore, global warming may
      lead to increasing frequencies and intensities of insect outbreaks. The aim of
      this work was to analyze the dynamics of the olive fruit fly, Bactrocera oleae
      (Rossi), in Tuscany (Italy). We profited from long-term records of insect
      infestation and weather data available from the regional database and
      agrometeorological network. We tested whether the analysis of 13 years of
      monitoring campaigns can be used as basis for prediction models of B. oleae
      infestation. We related the percentage of infestation observed in the first part
      of the host-pest interaction and throughout the whole year to agrometeorological
      indices formulated for different time periods. A two-step approach was adopted to
      inspect the effect of weather on infestation: generalized linear model with a
      binomial error distribution and principal component regression to reduce the
      number of the agrometeorological factors and remove their collinearity. We found
      a consistent relationship between the degree of infestation and the temperature
      based indices calculated for the previous period. The relationship was stronger
      with the minimum temperature of winter season. Higher infestation was observed in
      years following warmer winters. The temperature of the previous winter and spring
      explained 66 % of variance of early-season infestation. The temperature of
      previous winter and spring, and current summer, explained 72 % of variance of
      total annual infestation. These results highlight the importance of multiannual
      monitoring activity to fully understand the dynamics of B. oleae populations at a
      regional scale.

PMID- 27044275
TI  - Primary site and regional lymph node involvement are independent prognostic
      factors for early-stage extranodal nasal-type natural killer/T cell lymphoma.
AB  - BACKGROUND: Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL)
      originates primarily in the nasal cavity or extra-nasal sites within the upper
      aerodigestive tract. However, it is unclear whether the primary site can serve as
      an independent prognostic factor or whether the varying clinical outcomes
      observed with different primary sites can be attributed merely to their
      propensities of regional lymph node involvement. The aim of this study was to
      investigate the prognostic implications of the primary site and regional lymph
      node involvement in patients with early-stage nasal-type ENKTCL. METHODS: To
      develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed
      patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen
      University Cancer Center with chemotherapy and radiotherapy between 2000 and
      2011. The predictive accuracy and discriminative ability of the nomogram were
      determined using a concordance index (C-index) and calibration curve. RESULTS:
      The 5-year overall survival (OS) and progression-free survival (PFS) rates of
      patients with nasal ENKTCL were higher than those of patients with extra-nasal
      ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010). The 5
      year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than
      those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P =
      0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysis showed that age
      >60 years, ECOG performance status score >=2, elevated lactate dehydrogenase
      (LDH) level, extra-nasal primary site, and regional lymph node involvement were
      significantly associated with lower 5-year OS rate; age >60 years, elevated LDH
      level, extra-nasal primary site, and regional lymph node involvement were
      significantly associated with lower 5-year PFS rate. The nomogram included the
      primary site and regional lymph node involvement based on multivariate analysis.
      The calibration curve showed good agreement between the predicted and actual 5
      year OS and PFS rates, and the C-indexes of the nomogram for the OS and PFS rates
      were 0.697 and 0.634, respectively. CONCLUSIONS: The primary site and regional
      lymph node involvement are independent prognostic factors for early-stage ENKTCL
      treated with chemotherapy followed by definitive radiotherapy.

PMID- 27044276
TI  - Correlation between optic nerve head circulation and visual function before and
      after anti-VEGF therapy for central retinal vein occlusion: prospective,
      interventional case series.
AB  - BACKGROUND: To determine the correlation between the optic nerve head (ONH)
      circulation determined by laser speckle flowgraphy and the best-corrected visual
      acuity or retinal sensitivity before and after intravitreal bevacizumab or
      ranibizumab for central retinal vein occlusion. METHODS: Thirty-one eyes of 31
      patients were treated with intravitreal bevacizumab or ranibizumab for macular
      edema due to a central retinal vein occlusion. The blood flow in the large
      vessels on the ONH, the best-corrected visual acuity, and retinal sensitivity
      were measured at the baseline, and at 1, 3, and 6 months after treatment. The
      arteriovenous passage time on fluorescein angiography was determined. The venous
      tortuosity index was calculated on color fundus photograph by dividing the length
      of the tortuous retinal vein by the chord length of the same segment. The blood
      flow was represented by the mean blur rate (MBR) determined by laser speckle
      flowgraphy. To exclude the influence of systemic circulation and blood flow in
      the ONH tissue, the corrected MBR was calculated as MBR of ONH vessel area - MBR
      of ONH tissue area in the affected eye divided by the vascular MBR - tissue MBR
      in the unaffected eye. Pearson's correlation tests were used to determine the
      significance of correlations between the MBR and the best-corrected visual
      acuity, retinal sensitivity, arteriovenous passage time, or venous tortuosity
      index. RESULTS: At the baseline, the corrected MBR was significantly correlated
      with the arteriovenous passage time and venous tortuosity index (r = -0.807, P <
      0.001; r = -0.716, P < 0.001; respectively). The corrected MBR was significantly
      correlated with the best-corrected visual acuity and retinal sensitivity at the
      baseline, and at 1, 3, and 6 months (all P < 0.050). The corrected MBR at the
      baseline was significantly correlated with the best-corrected visual acuity at 6
      months (r = -0.651, P < 0.001) and retinal sensitivity at 6 months (r = 0.485, P
      = 0.005). CONCLUSIONS: The pre-treatment blood flow velocity of ONH can be used
      as a predictive factor for the best-corrected visual acuity and retinal
      sensitivity after anti-VEGF therapy for central retinal vein occlusion. TRIAL
      REGISTRATION:  TRIAL REGISTRATION NUMBER: UMIN000009072. Date of registration:
      10/15/2012.

PMID- 27044277
TI  - Application of Correlated Time-to-Event Models to Ecological Momentary Assessment
      Data.
AB  - Ecological momentary assessment data consist of in-the-moment sampling several
      times per day aimed at capturing phenomena that are highly variable. When
      research questions are focused on the association between a construct measured
      repeatedly and an event that occurs sporadically over time interspersed between
      repeated measures, the data consist of correlated observed or censored times to
      an event. In such a case, specialized time-to-event models that account for
      correlated observations are required to properly assess the relationships under
      study. In the current study, we apply two time-to-event analysis techniques,
      proportional hazards, and accelerated failure time modeling, to data from a study
      of affective states and sexual behavior in depressed adolescents and illustrate
      differing interpretations from the models.

PMID- 27044278
TI  - Vectors for Zika virus may spread further than was previously thought, CDC
      reports.

PMID- 27044279
TI  - Qigong in cancer care: a systematic review and construct analysis of effective
      Qigong therapy.
AB  - PURPOSE: This review (a) assesses the strength of evidence addressing Qigong
      therapy in supportive cancer care and (b) provides insights for definition of
      effective Qigong therapy in supportive cancer care. METHODS: This mixed-methods
      study includes (a) a systematic review of randomized clinical trials (RCTs)
      following PRISMA guidelines and (b) a constant-comparative qualitative analysis
      of effective intervention protocols. RESULTS: Eleven published randomized
      clinical trials were reviewed. A total of 831 individuals were studied.
      Geographic settings include the USA, Australia, China, Hong Kong, and Malaysia.
      Qigong therapy was found to have positive effects on the cancer-specific QOL,
      fatigue, immune function, and cortisol levels of individuals with cancer. Qigong
      therapy protocols varied supporting a plurality of styles. Qualitative analyses
      identified common programming constructs. Content constructs included exercise
      (gentle, integrated, repetitious, flowing, weight-bearing movements), breath
      regulation, mindfulness and meditation, energy cultivation including self
      massage, and emphasis on relaxation. Logistic constructs included delivery by
      qualified instructors, home practice, and accommodation for impaired activity
      tolerance. CONCLUSIONS: There is global interest and a growing body of research
      providing evidence of therapeutic effect of Qigong therapy in supportive cancer
      care. While Qigong therapy protocols vary in style, construct commonalities do
      exist. Knowledge of the common constructs among effective programs revealed in
      this research may be used to guide future research intervention protocol and
      community programming design and development.

PMID- 27044280
TI  - Effect of preoperative injection of carbon nanoparticle suspension on the
      outcomes of selected patients with mid-low rectal cancer.
AB  - BACKGROUND: Carbon nanoparticles show significant lymphatic tropism and can be
      used to identify lymph nodes surrounding mid-low rectal tumors. In this study, we
      analyzed the effect of trans anal injection of a carbon nanoparticle suspension
      on the outcomes of patients with mid-low rectal cancer who underwent laparoscopic
      resection. METHODS: We collected the data of 87 patients with mid-low rectal
      cancer who underwent laparoscopic resection between November 2014 and March 2015
      at Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical
      College. For 35 patients in the experimental group, the carbon nanoparticle
      suspension was injected transanally into the submucosa of the rectum around the
      tumor 30 min before the operation; 52 patients in the control group underwent the
      operation directly without the injection of carbon nanoparticle suspension. We
      then compared the operation outcomes between the two groups. RESULTS: In the
      experimental group, the rate of incomplete mesorectal excision was lower than
      that in the control group, but no significant difference was found (2.9% vs.
      7.7%, P = 0.342). The distance between the tumor and the circumferential
      resection margin was 5.8 +/- 1.4 mm in the experimental group and 4.8 +/- 1.1 mm
      in the control group (P = 0.001). The mean number of lymph nodes removed was 28.2
      +/- 9.4 in the experimental group and 22.7 +/- 7.3 in the control group (P =
      0.003); the mean number of lymph nodes smaller than 5 mm in diameter was 10.1 +/-
      7.5 and 4.5 +/- 3.7, respectively (P < 0.001). Three patients in the experimental
      group received lateral lymph node resection. Among the three patients, we
      retrieved three nodes (one stained node) from the first patient, three nodes (two
      stained nodes) from the second patient, and two nodes (no stained nodes) from the
      third patient. CONCLUSIONS: Injecting a carbon nanoparticle suspension improved
      the outcomes of patients who underwent laparoscopic resection for mid-low rectal
      cancer; it also improved the accuracy of pathologic staging. Moreover, for
      selected patients, this technique narrowed the scope of lateral lymph node
      dissection.

PMID- 27044281
TI  - Delayed-onset descemet membrane detachment after uneventful cataract surgery
      treated by corneal venting incision with air tamponade: a case report.
AB  - BACKGROUND: Descemet membrane detachment (DMD) is a significant complication
      noted during or early after cataract surgery. Review of literature revealed a few
      cases of delayed-onset DMD with presentation ranging from weeks to months after
      cataract surgery but most of them were treated with pneumatic descemetopexy and a
      few ended in penetrating keratoplasty. We report this case, to highlight the
      usefulness of corneal venting incision with air tamponade in late-onset DMD cases
      not responding to pneumatic descemetopexy. CASE PRESENTATION: A retrospective
      case review of a 66 year old male who presented with diminution of vision in
      right eye 17 days after uneventful cataract surgery was done. Visual acuity in
      this eye was 20/200 at presentation. DMD was noted 3 days later (approximately 3
      weeks post-operatively) and Anterior Segment Optical Coherence Tomography &
      Scheimpflug imaging were done in view of diffuse corneal edema. Pneumatic
      descemetopexy was attempted thrice (twice with SF6, once with air) over a week's
      span with limited success at re-attaching the DM. Finally, corneal venting
      incision with air tamponade was done resulting in egress of supra-descemet's
      fluid and DM appeared apposed to stroma. Bandage contact lens (BCL) was applied
      at the end of the procedure. DM was seen attached the next day. Corneal edema
      cleared completely in 1 week. Best corrected visual acuity (BCVA) at 6 weeks
      follow-up was 20/30. CONCLUSION: Delayed-onset DMD should be considered as a
      differential diagnosis in cases with late-onset corneal edema post-cataract
      surgery. Anterior segment Optical Coherence Tomography (AS-OCT) and Scheimpflug
      Imaging are useful tools in cases with dense corneal edema. Corneal venting
      incision with air tamponade is an option in cases where methods like pneumatic
      descemetopexy fail.

PMID- 27044282
TI  - Outcomes after planned invasive or conservative treatment strategy in patients
      with non-ST-elevation acute coronary syndrome and a normal value of high
      sensitivity troponin at randomisation: A Platelet Inhibition and Patient Outcomes
      (PLATO) trial biomarker substudy.
AB  - AIMS: Current guidelines for patients with non-ST-elevation acute coronary
      syndrome (NSTE-ACS) recommend early invasive treatment in intermediate-to-high
      risk patients based on medical history, electrocardiogram (ECG) and elevated
      troponin. Patients with normal levels of cardiac troponin measured with a high
      sensitivity method (cTnT-hs) might not benefit from early invasive procedures.
      METHODS AND RESULTS: In this Prospective Randomized Platelet Inhibition and
      Patient Outcomes (PLATO) blood-core substudy, 1232 patients presented with NSTE
      ACS had a high sensitivity cardiac troponin T (cTnT-hs) level <99th percentile
      (<14 ng/l) at randomisation. The outcomes in relation to a planned invasive (
      n=473) vs planned conservative treatment ( n=759), were evaluated by adjusted Cox
      proportional hazard analyses. In patients with a normal cTnT-hs at randomisation,
      regardless of randomised treatment, a planned invasive vs conservative treatment
      was associated with a 2.3-fold higher risk (7.3% vs 3.4%, p=0.0028) for
      cardiovascular (CV) death or myocardial infarction (MI), driven by higher rates
      of procedure-related MI (3.4% vs 0.1%), while there were no differences in rates
      of CV death (1.3% vs 1.3%, p=0.72) or spontaneous MI (3.0% vs 2.1%, p=0.28).
      There were significantly more major bleeds (hazard ratio (HR) 2.98, p<0.0001),
      mainly due to coronary artery bypass graft (CABG)-related (HR 4.05, p<0.0001) and
      non-CABG procedural-related major bleeding events (HR 5.31, p=0.0175), however
      there were no differences in non-procedure-related major bleeding (1.5% vs 1.9%,
      p=0.45). Findings were consistent for patients with a normal cTnI-hs at
      randomisation. CONCLUSIONS: In patients with NSTE-ACS and normal cTnT-hs, a
      planned early invasive treatment strategy was associated with increased rates of
      procedure-related MI and bleeding but no differences in long-term spontaneous MI,
      non-procedure-related bleeding or mortality.

PMID- 27044283
TI  - The ICMJE Recommendations and pharmaceutical marketing--strengths, weaknesses and
      the unsolved problem of attribution in publication ethics.
AB  - BACKGROUND: The International Committee of Medical Journal Editors (ICMJE)
      Recommendations set ethical and editorial standards for article publication in
      most leading medical journals. Here, I examine the strengths and weaknesses of
      the Recommendations in the prevention of commercial bias in industry-financed
      journal literature, on three levels - scholarly discourse, article content, and
      article attribution. DISCUSSION: With respect to overall discourse, the most
      important measures in the ICMJE Recommendations are for enforcing clinical trial
      registration and controlling duplicate publication. With respect to article
      content, the ICMJE promotes stringent author accountability and adherence to
      established reporting standards. However, the ICMJE accepts the use of commercial
      editorial teams to produce manuscripts, which is a potential source of bias, and
      accepts private company ownership and analysis of clinical trial data. New ICMJE
      guidance on data sharing will address but not eliminate problems of commercial
      data access. With respect to attribution, the Recommendations oppose guest
      authorship and encourage clear documentation of author contributions. However,
      they exclude writers from coauthorship; provide no specific advice on the
      attribution of commercial literature, for instance with respect to company
      authorship, author sequence or prominent commercial labeling; and endorse the use
      of fine print and euphemism. The ICMJE requires detailed author interest
      disclosures, but overlooks the interests of non-authors and companies, and does
      not recommend that interests most salient to the publication are highlighted.
      Together, these weaknesses facilitate "advocacy"-based marketing, in which
      literature planned, financed and produced by companies is fronted by academics,
      enabling commercial messages to be presented to customers by their respected
      clinical peers rather than companies themselves. CONCLUSIONS: The ICMJE
      Recommendations set important research and reporting standards, without which
      commercial bias would likely be a significantly greater problem than it is today.
      However, they also support practices of commercial data control, content
      development and attribution that run counter to science's values of openness,
      objectivity and truthfulness. These weaknesses could be addressed with
      appropriate modifications to the Recommendations. The ICMJE should also disclose
      its own commercial interests and funding - not least because publishing
      organizations that finance it and pay the salaries of some member editors derive
      substantial revenues from industry.

PMID- 27044284
TI  - Transantral endoscopic approach for the treatment of lesions affecting the
      maxillary nerve.
AB  - BACKGROUND: Surgical approaches to skull base lesions that affect the maxillary
      nerve are complex, due to deep location and presence of relevant neurovascular
      structures surrounding this area. METHOD: We propose the transantral endoscopic
      approach (TEA) for the treatment of lesions affecting the maxillary nerve or its
      vicinity. More specifically, the ones that are located anterior to the foramen
      rotundum. CONCLUSIONS: This technique represents a minimally invasive treatment
      option for these kind of cranial base lesions. It offers optimal visualisation
      similar to the endonasal approach, whereas less dissection is required.

PMID- 27044285
TI  - Prospective study found that peripheral lymph node sampling reduced the false
      negative rate of sentinel lymph node biopsy for breast cancer.
AB  - BACKGROUND: Although sentinel lymph node biopsy (SLNB) can accurately predict the
      status of axillary lymph node (ALN) metastasis, the high false-negative rate
      (FNR) of SLNB is still the main obstacle for the treatment of patients who
      receive SLNB instead of ALN dissection (ALND). The purpose of this study was to
      evaluate the clinical significance of SLNB combined with peripheral lymph node
      (PLN) sampling for reducing the FNR for breast cancer and to discuss the effect
      of "skip metastasis" on the FNR of SLNB. METHODS: At Shandong Cancer Hospital
      Affiliated to Shandong University between March 1, 2012 and June 30, 2015, the
      sentinel lymph nodes (SLNs) of 596 patients with breast cancer were examined
      using radiocolloids with blue dye tracer. First, the SLNs were removed; then, the
      area surrounding the original SLNs was selected, and the visible lymph nodes in a
      field of 3-5 cm in diameter around the center (i.e., PLNs) were removed, avoiding
      damage to the structure of the breast. Finally, ALND was performed. The SLNs,
      PLNs, and remaining ALNs underwent pathologic examination, and the relationship
      between them was analyzed. RESULTS: The identification rate of SLNs in the 596
      patients was 95.1% (567/596); the metastasis rate of ALNs was 33.7% (191/567);
      the FNR of pure SLNB was 9.9% (19/191); and after the SLNs and PLNs were
      eliminated, the FNR was 4.2% (8/191), which was significantly decreased compared
      with the FNR before removal of PLNs (P = 0.028). According to the detected number
      (N) of SLNs, the patients were divided into four groups of N = 1, 2, 3, and >=4;
      the FNR in these groups was 19.6, 9.8, 7.3, and 2.3%, respectively. For the
      patients with <=2 or <=3 detected SLNs, the FNR after removal of PLNs was
      significantly decreased compared with that before removal of PLNs (N <= 2: 14.0%
      vs. 4.7%, P = 0.019; N <= 3: 12.2% vs. 4.7%, P = 0.021), whereas for patients
      with >=4 detected SLNs, the decrease in FNR was not statistically significant (P
      = 1.000). In the entire cohorts, the "skip metastasis" rate was 2.5% (15/596);
      the FNR caused by "skip metastasis" was 2.1% (4/191). CONCLUSIONS: The FNR of
      SLNB was associated with the number of SLNs. For patients with <=3 detected SLNs,
      PLN sampling can reduce the FNR of SLNB to an acceptable level of less than 5%.
      Because of the existence of the "skip metastasis" and distinct metastasis
      patterns, the FNR of SLNB cannot be completely eliminated.

PMID- 27044286
TI  - In vitro quantitative determination of the concentration of the polymerization
      agent methyl 2-benzoylbenzoate in intravenous injection solution and the
      cytotoxic effects of the chemical on normal human peripheral blood mononuclear
      cells.
AB  - In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl
      ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) in
      an intravenous injection solution. Importantly, 1-HCHPK and MTMP have been
      demonstrated to be cytotoxic to normal human peripheral blood (PB) mononuclear
      cells (MNC). Cell death (apoptosis) pathways can be classified into two modes,
      caspase-dependent and -independent pathways. However, it is unclear whether
      methyl 2-benzoylbenzoate (MBB) induces the caspase-dependent and/or -independent
      pathway in normal human PBMNC. In the present in vitro study, we examined the
      levels of MBB in a solution from an intravenous fluid bag and the cytotoxicity of
      MBB towards normal human PBMNC via the caspase-8-, caspase-9-, or apoptosis
      inducing factor (AIF)-mediated apoptosis pathways. We found that extracts from
      the injection solution had been contaminated with approximately 80 MUM of the
      photoinitiator MBB. In addition, MBB induced apoptosis in the high concentration
      range in normal human PBMNC in vitro. Moreover, we found that MBB-induced
      apoptosis occurs via the caspase-9 pathway, but not the AIF pathway. In
      conclusion, we suggest that MBB has cytotoxic effects on normal human PBMNC in
      vitro, which are mediated via the caspase-dependent pathway. 

PMID- 27044287
TI  - Biodegradation of compostable and oxodegradable plastic films by backyard
      composting and bioaugmentation.
AB  - Plastics are widely used in the production of short-life products, which are
      discarded producing an accumulation of these materials and problems due to their
      persistence in the environment and waste management systems. Degradable plastics
      (compostable, oxodegradable) have been presented as an alternative to decrease
      the negative effect of plastic waste. In this research, the feasibility of
      degrading a commercially available compostable film and oxodegradable
      polyethylene, with and without previous abiotic oxidation, is assessed in a home
      composting system. Reactors (200 L) were used to degrade the plastic films along
      with a mixture of organic food waste (50 %), mulch (25 %), and dry leaves (25 %),
      amended with yeast and a solution of brown sugar to increase the speed of the
      process. The presence of the plastic film did not affect the composting process,
      which showed an initial increase in temperature and typical profiles for moisture
      content, pH, with a final C/N of 17.4. After 57 days, the compostable plastic has
      decreased its mechanical properties in more than 90 %, while the oxodegradable
      film did not show significant degradation if it was not previously degraded by UV
      radiation. The use of these plastics should be assessed against the prevailing
      waste management system in each city or country. In the case of Mexico, which
      lacks the infrastructure for industrial composting, home composting could be an
      option to degrade compostable plastics along organic waste. However, more testing
      is needed in order to set the optimal parameters of the process.

PMID- 27044288
TI  - Optimization of lipid extraction from Salvinia molesta for biodiesel production
      using RSM and its FAME analysis.
AB  - The higher areal productivity and lipid content of microalgae and aquatic weed
      makes them the best alternative feedstocks for biodiesel production. Hence, an
      efficient and economic method of extracting lipid or oil from aquatic weed,
      Salvinia molesta is an important step towards biodiesel production. Since
      Salvinia molesta is an unexplored feedstock, its total lipid content was first
      measured as 16 % using Bligh and Dyer's method which was quite sufficient for
      further investigation. For extracting more amount of lipid from Salvinia molesta,
      methanol: chloroform in the ratio 2:1 v/v was identified as the most suitable
      solvent system using Soxhlet apparatus. Based on the literature and the
      preliminary experimentations, parameters such as solvent to biomass ratio,
      temperature, and time were identified as significant for lipid extraction. These
      parameters were then optimized using response surface methodology with central
      composite design, where experiments were performed using twenty combinations of
      these extraction parameters with Minitab-17 software. A lipid yield of 92.4 %
      from Salvinia molesta was obtained with Soxhlet apparatus using methanol and
      chloroform (2:1 v/v) as solvent system, at the optimized conditions of
      temperature (85  degrees C), solvent to biomass ratio (20:1), and time (137 min),
      whereas a predicted lipid yield of 93.5 % with regression model. Fatty acid
      methyl ester (FAME) analysis of S. molesta lipid using gas chromatograph mass
      spectroscopy (GCMS) with flame ionization detector showed that fatty acids such
      as C16:0, C16:1, C18:1, and C18:2 contributed more than 9 % weight of total fatty
      acids. FAME consisted of 56.32, 28.08, and 15.59 % weight of monounsaturated,
      saturated, and polyunsaturated fatty acids, respectively. Higher cetane number
      and superior oxidation stability of S. molesta FAME could be attributed to its
      higher monounsaturated content and lower polyunsaturated content as compared to
      biodiesels produced from C. vulgaris, Sunflower, and Jatropha. 

PMID- 27044289
TI  - Trends and variability in blood lead concentrations among US adults aged 20-64
      years and senior citizens aged >=65 years.
AB  - Using data from National Health and Nutrition Examination Survey for the period
      2003-2012, the objective of this study was to evaluate trends in blood lead
      levels (BLL) among adults aged 20-64 years (adults) and seniors aged >=65 years
      (seniors). In addition, the contribution of other factors like gender,
      race/ethnicity, smoking, and exposure to secondhand smoke at home in explaining
      variability in BLL was also evaluated by fitting regression models with log10
      transformed values of BLL as dependent variables. BLL decreased over 2003-2012 (p
      < 0.01). Irrespective of gender, race/ethnicity, and smoking status, seniors were
      found to have higher BLL than adults. Based on the magnitude of differences
      between the 5th and 95th percentiles, variability in the levels of blood lead was
      found to be substantially higher among seniors than among adults. Males had
      statistically significantly higher adjusted BLL than females (2.32 vs. 1.76
      MUg/dL for seniors, p < 0.01 and 1.66 vs. 1.13 MUg/dL for adults, p < 0.01). Non
      Hispanic whites had statistically significantly lower adjusted BLL than non
      Hispanic blacks (1.99 vs. 2.42 MUg/dL for seniors, p < 0.01 and 1.22 vs. 1.42
      MUg/dL for adults, p < 0.01). When compared with non-smokers, smokers had
      statistically significantly higher BLL (2.19 vs. 1.86 MUg/dL for seniors, p <
      0.01 and 1.54 vs. 1.22 MUg/dL for adults, p < 0.01). Non-obese had statistically
      significantly higher BLL than obese individuals (2.11 vs. 1.93 MUg/dL for
      seniors, p < 0.01 and 1.48 vs. 1.27 MUg/dL for adults, p < 0.01). Exposure to
      secondhand smoke at home (SHS) was associated with statistically significantly
      higher BLL than when there was no exposure to SHS (beta = 0.0683, p = 0.03 for
      seniors; beta = 0.034, p = 0.034, p < 0.01 for adults). 

PMID- 27044290
TI  - Development of fast and robust multiresidual LC-MS/MS method for determination of
      pharmaceuticals in soils.
AB  - The aim of this study was to develop a simple extraction procedure and a
      multiresidual liquid chromatography-tandem mass spectrometry method for
      determination of a wide range of pharmaceuticals from various soil types. An
      extraction procedure for 91 pharmaceuticals from 13 soil types, followed by
      liquid chromatography-tandem mass spectrometry analysis, was optimized. The
      extraction efficiencies of three solvent mixtures for ultrasonic extraction were
      evaluated for 91 pharmaceuticals. The best results were obtained using
      acetonitrile/water (1/1 v/v with 0.1 % formic acid) followed by acetonitrile/2
      propanol/water (3/3/4 v/v/v with 0.1 % formic acid) for extracting 63
      pharmaceuticals. The method was validated at three fortification levels (10, 100,
      and 1000 ng/g) in all types of representative soils; recovery of 44
      pharmaceuticals ranged between 55 and 135 % across all tested soils. The method
      was applied to analyze actual environmental samples of sediments, soils, and
      sludge, and 24 pharmaceuticals were found above limit of quantification with
      concentrations ranging between 0.83 ng/g (fexofenadine) and 223 ng/g
      (citalopram). 

PMID- 27044291
TI  - Typha latifolia (broadleaf cattail) as bioindicator of different types of
      pollution in aquatic ecosystems-application of self-organizing feature map
      (neural network).
AB  - The contents of Cd, Cu, Fe, Mn, Ni, Pb, and Zn in leaves of Typha latifolia
      (broadleaf cattail), water and bottom sediment from 72 study sites designated in
      different regions of Poland were determined using atomic absorption spectrometry.
      The aim of the study was to evaluate potential use of T. latifolia in
      biomonitoring of trace metal pollution. The self-organizing feature map (SOFM)
      identifying groups of sampling sites with similar concentrations of metals in
      cattail leaves was able to classify study sites according to similar use and
      potential sources of pollution. Maps prepared for water and bottom sediment
      showed corresponding groups of sampling sites which suggested similarity of
      samples features. High concentrations of Fe, Cd, Cu, and Ni were characteristic
      for industrial areas. Elevated Pb concentrations were noted in regions with
      intensive vehicle traffic, while high Mn and Zn contents were reported in leaves
      from the agricultural area. Manganese content in leaves of T. latifolia was high
      irrespectively of the concentrations in bottom sediments and water so cattail can
      be considered the leaf accumulator of Mn. Once trained, SOFMs can be applied in
      ecological investigations and could form a future basis for recognizing the type
      of pollution in aquatic environments by analyzing the concentrations of elements
      in T. latifolia. 

PMID- 27044292
TI  - Photocatalytic processes assisted by artificial solar light for soil washing
      effluent treatment.
AB  - Contaminated soil has become a growing issue in recent years. The most common
      technique used to remove contaminants (such as metals) from the soil is the soil
      washing process. However, this process produces a final effluent containing
      chelating agents (i.e., ethylenediaminedisuccinic acid, also known as EDDS) and
      extracted metals (i.e., Cu, Fe, and Zn) at concentrations higher than discharge
      limits allowed by the Italian and Brazilian environmental law. Therefore, it is
      necessary to develop further treatments before its proper disposal or reuse. In
      the present study, soil washing tests were carried out through two sequential
      paths. Moreover, different artificial sunlight-driven photocatalytic treatments
      were used to remove Cu, Zn, Fe, and EDDS from soil washing effluents. Metal
      concentrations after the additional treatment were within the Brazilian and
      Italian regulatory limits for discharging in public sewers. The combined TiO2
      photocatalytic processes applied were enough to decontaminate the effluents,
      allowing their reuse in soil washing treatment. Ecotoxicological assessment using
      different living organisms was carried out to assess the impact of the proposed
      two-step photocatalytic process on the effluent ecotoxicity. Graphical Abstract
      ?.

PMID- 27044293
TI  - Atmospheric deposition of rare earth elements in Albania studied by the moss
      biomonitoring technique, neutron activation analysis and GIS technology.
AB  - Rare earth elements (REEs) are typically conservative elements that are scarcely
      derived from anthropogenic sources. The mobilization of REEs in the environment
      requires the monitoring of these elements in environmental matrices, in which
      they are present at trace level. The determination of 11 REEs in carpet-forming
      moss species (Hypnum cupressiforme) collected from 44 sampling sites over the
      whole territory of the country were done by using epithermal neutron activation
      analysis (ENAA) at IBR-2 fast pulsed reactor in Dubna. This paper is focused on
      REEs (lanthanides) and Sc. Fe as typical consistent element and Th that appeared
      good correlations between the elements of lanthanides are included in this paper.
      Th, Sc, and REEs were never previously determined in the air deposition of
      Albania. Descriptive statistics were used for data treatment using MINITAB 17
      software package. The median values of the elements under investigation were
      compared with those of the neighboring countries such as Bulgaria, Macedonia,
      Romania, and Serbia, as well as Norway which is selected as a clean area.
      Geographical distribution maps of the elements over the sampled territory were
      constructed using geographic information system (GIS) technology. Geochemical
      behavior of REEs in moss samples has been studied by using the ternary diagram of
      Sc-La-Th, Spider diagrams and multivariate analysis. It was revealed that the
      accumulation of REEs in current mosses is associated with the wind-blowing metal
      enriched soils that is pointed out as the main emitting factor of the elements
      under investigation. 

PMID- 27044294
TI  - Insulin-like growth factor binding protein-2 regulates beta-catenin signaling
      pathway in glioma cells and contributes to poor patient prognosis.
AB  - BACKGROUND: Upregulation of insulin-like growth factor binding protein 2 (IGFBP
      2) is often associated with aggressiveness of glioblastoma (GBM) and contributes
      to poor prognosis for GBM patients. In view of the regulation of beta-catenin by
      IGFBP-2 in breast cancer and the crucial role of beta-catenin pathway in glioma
      invasion, proliferation and maintenance of glioma stem cells, the mechanism of
      regulation of beta-catenin by IGFBP-2, and its role in GBM prognosis was studied.
      METHODS: Regulation of the beta-catenin pathway was studied by
      immunocytochemistry, Western blot analysis, luciferase assays, and real-time RT
      PCR. The role of IGFBP-2 was studied by subcutaneous tumor xenografts in
      immunocompromised mice using glioma cells engineered to express IGFBP-2 and its
      domains. GBM patient tumor tissues (n = 112) were analyzed for expression of
      IGFBP-2 and beta-catenin by immunohistochemistry. Survival analysis was performed
      employing Cox regression and Kaplan-Meier survival analyses. RESULTS: IGFBP-2
      knockdown in U251, T98G, and U373 or overexpression in LN229 and U87 cells
      revealed a role for IGFBP-2 in stabilization of beta-catenin and regulation of
      its nuclear functions involving integrin-mediated inactivation of GSK3beta.
      Similar results were obtained upon overexpression of the C-terminal domain of
      IGFBP-2 but not the N-terminal domain. Subcutaneous xenograft tumors
      overexpressing either full-length or the C-terminal domain of IGFBP-2 showed
      larger volume as compared with controls. Coexpression of high levels of IGFBP-2
      and beta-catenin was associated with worse prognosis (P = .001) in GBM patients.
      CONCLUSION: IGFBP-2 potentiates GBM tumor growth by the activation of the beta
      catenin pathway through its C-terminal domain, and their coexpression possibly
      contributes to worse patient prognosis.

PMID- 27044295
TI  - Toward an integrated histomolecular diagnosis of supratentorial ependymoma.

PMID- 27044296
TI  - Fatigue randomized controlled trials-how tired is "too tired" in patients
      undergoing glioma treatment?

PMID- 27044297
TI  - Doctor is struck off after third fitness to practise hearing.

PMID- 27044298
TI  - Use your antibiotics wisely. Consequences to the intestinal microbiome.
AB  - Antibiotic therapy has long term consequences in the intestinal microbiome.
      Clostridium difficile has a well-known role in antibiotic-associated diarrhea,
      but in addition, persistent infection with this organism may increase the risk
      for developing inflammatory bowel disease. Here, recent literature on how the
      intestinal microbiome is altered by antibiotic therapy is presented.

PMID- 27044299
TI  - The major autolysin is redundant for Staphylococcus aureus USA300 LAC JE2
      virulence in a murine device-related infection model.
AB  - The major Staphylococcus aureus autolysin, Atl, has been implicated in attachment
      to surfaces and release of extracellular DNA during biofilm formation under
      laboratory conditions. Consistent with this, polyclonal antibodies to the amidase
      and glucosaminidase domains of Atl inhibited in vitro biofilm formation. However,
      in a murine model of device-related infection the community-associated S. aureus
      strain USA300 LAC JE2 established a successful infection in the absence of atl
      These data indicate that Atl activity is not required for biofilm production in
      this infection model and reveal the importance of characterizing the contribution
      of biofilm phenotypes to virulence under in vivo conditions.

PMID- 27044300
TI  - Detection and quantification of virulent Aeromonas hydrophila in channel catfish
      tissues following waterborne challenge.
AB  - The aim of this study was to understand the pathogenesis of motile aeromonas
      septicemia caused by an emergent, high virulent Aeromonas hydrophila (vAh) in
      channel catfish, Ictalurus punctatus Adipose fin clipped catfish were challenged
      with vAh using a waterborne challenge method, and the distribution of vAh over a
      time course was detected and quantified using real-time polymerase chain
      reaction. The results showed that 77.8% of fish died within 48 h post challenge
      with mean day to death of 1.5 days. At 2 h post challenge, vAh (inferred from
      genomic DNA copies or genome equivalents) was detected in all external and
      internal tissues sampled. Gill had the highest vAh cells at 1 h post challenge.
      Spleen harbored the most vAh cells among internal organs at 4 h post challenge.
      The tissues/organs with most vAh cells detected at 8 h post challenge were
      adipose fin, blood, intestine, kidney and skin, while liver showed the highest
      vAh cells at 24 h post challenge. These results suggest that vAh was able to
      rapidly proliferate and spread, following wound infection, through the fish blood
      circulation system and cause mortality within 8-24 h.

PMID- 27044301
TI  - Manual aiming in healthy aging: does proprioceptive acuity make the difference?
AB  - The present study examines whether non-active older adults are more dependent on
      visual information when executing aiming movements and whether age-related
      declines in proprioception play a mediating role herein. Young (N = 40) and older
      adults (N = 38) were divided into physically active and non-active subgroups
      based on self-reported sports participation levels. In experiment 1, participants
      executed wrist-aiming movements with and without visual feedback. In experiment
      2, passive proprioceptive acuity was assessed using wrist motion detection and
      position matching tests. Results showed similar aiming accuracy across age groups
      both with and without visual feedback, but older adults exhibited longer movement
      times, prolonged homing-in phase, and made more corrective submovements. Passive
      proprioceptive acuity was significantly affected by physical activity level and
      age, with participants in the active group scoring better than their non-active
      peers. However, these declines did not predict performance changes on the aiming
      task. Taken together, our observations suggest that decline in proprioceptive
      acuity did not predict performance changes on the aiming task and older adults
      were able to compensate for their decreased motion and position sense when
      allowed sufficient time. In line with these observations, we proposed that older
      adults are able to compensate for their decline in proprioception by increasing
      their reliance on predictive models. 

PMID- 27044302
TI  - Ecological population genomics in the marine environment.
AB  - Marine species live in a wide diversity of environments and yet, because of their
      pelagic life stages, are thought to be well-connected: they have high migration
      rates that inhibit significant population structure. Recent innovations in
      sequencing technologies now provide information on nucleotide polymorphisms at
      thousands to tens of thousands of loci based on whole genomes, reduced
      representative portions of genomes (0.1-1%) or a majority of expressed mRNAs.
      Data from these genomic approaches are used to define and quantify single
      nucleotide polymorphisms (SNPs). These SNP data tend to agree with data from
      older technologies (allozymes or microsatellites), which support well-connected
      populations with few genetic differences among populations. However, these
      studies also find few percentages of SNPs (1-5%) that readily distinguish genetic
      differences among populations on relatively small geographic scales. The
      magnitudes of the genetic differences (FST values) suggest that hundreds of loci
      with significant differences are due to positive selective pressures. Thus, these
      data suggest that natural selection is effectively altering allele frequencies at
      100s of loci in marine populations. In this manuscript, we provide examples of
      these studies, the strengths and weaknesses of different genomic approaches as
      well as important technical aspects associated with genomic approaches. 

PMID- 27044303
TI  - Erratum to: The effectiveness of substitution of hospital ward care from medical
      doctors to physician assistants: a study protocol.

PMID- 27044304
TI  - Web-based cognitive behavioral relapse prevention program with tailored feedback
      for people with methamphetamine and other drug use problems: protocol for a
      multicenter randomized controlled trial in Japan.
AB  - BACKGROUND: Despite the effectiveness of psychosocial programs for recovery from
      drug use problems, there have been challenges in implementation of treatment.
      Internet-based and computerized approaches have been known to be effective in
      treatment dissemination. The study purpose is to assess the effects of a web
      based psychosocial relapse prevention program with a multicenter randomized
      controlled trial. METHODS: Recruitment began in January 2015 for outpatient
      participants diagnosed with drug abuse or dependence who have used a primary
      abused drug in the past year at psychiatric hospitals and a clinic. Participants
      are randomized either to a web-based relapse prevention program or a self
      monitoring group. The intervention is a web-based relapse prevention program
      named "e-SMARPP" that consists of six relapse prevention program modules with
      tailored feedback from health care professionals and 8 weeks of self-monitoring.
      The content is adapted from a face-to-face relapse prevention program which is
      based on cognitive behavioral therapy and motivational enhancement. The primary
      outcomes are relapse risk assessed by the Stimulant Relapse Risk Scale (baseline,
      2-, 5- and 8-month) and the longest duration of consecutive abstinent days from
      primary abused drug during the intervention. Secondary outcomes will include
      motivation to change, self-efficacy for drug use and craving, abstinent days in
      the past 28 or 56 days, quality of life, sense of coherence, cost of substance
      use, medical cost, retention of treatment and use of self-help group. Completion,
      usability and satisfaction of the program will be also assessed to explore
      feasibility. This study protocol was approved by the Ethics Committee of The
      University of Tokyo and each recruiting hospital and clinic. DISCUSSION: To our
      knowledge, this study is the first clinical trial to assess the effects of a web
      based therapeutic program for drug users in Japan. If successful, this program is
      a promising approach for drug user treatment in Japan, where the stigma toward
      drug users is strong. The results are also useful for researchers who want to
      know about programs for various substances, including methamphetamine. TRIAL
      REGISTRATION: This trial was registered with the University Hospital Medical
      Information Network clinical trial registry: UMIN000016075 (Date of registration:
      January 5, 2015).

PMID- 27044305
TI  - Pathogenic effects of glucosyltransferase from Clostridium difficile toxins.
AB  - The glucosyltransferase domain ofClostridium difficiletoxins modifies guanine
      nucleotide-binding proteins of Rho family. It is the major virulent domain of the
      holotoxins. Various pathogenic effects ofC. difficiletoxins in response to Rho
      glucosylation have been investigated including cytoskeleton damage, cell death
      and inflammation. The most recent studies have revealed some significant
      characteristics of the holotoxins that are independent of glucosylating activity.
      These findings arouse discussion about the role of glucosyltransferase activity
      in toxin pathogenesis and open up new insights for toxin mechanism study. In this
      review, we summarize the pathogenic effects of glucosyltransferase domain of the
      toxins in the past years. 

PMID- 27044306
TI  - Solitary Nanostructures Produced by Ultrashort Laser Pulse.
AB  - Laser-produced surface nanostructures show considerable promise for many
      applications while fundamental questions concerning the corresponding mechanisms
      of structuring are still debated. Here, we present a simple physical model
      describing those mechanisms happened in a thin metal film on dielectric substrate
      irradiated by a tightly focused ultrashort laser pulse. The main ingredients
      included into the model are (i) the film-substrate hydrodynamic interaction,
      melting and separation of the film from substrate with velocity increasing with
      increase of absorbed fluence; (ii) the capillary forces decelerating expansion of
      the expanding flying film; and (iii) rapid freezing into a solid state if the
      rate of solidification is comparable or larger than hydrodynamic velocities. The
      developed model and performed simulations explain appearance of microbump inside
      the focal spot on the film surface. The model follows experimental findings about
      gradual transformation of the bump from small parabolic to a conical shape and to
      the bump with a jet on its tip with increasing fluence. Disruption of the bump as
      a result of thinning down the liquid film to a few interatomic distances or due
      to mechanical break-off of solid film is described together with the jetting and
      formation of one or many droplets. Developed theory opens door for optimizing
      laser parameters for intended nanostructuring in applications. 

PMID- 27044307
TI  - Preparation of Fe2O3-Clorprenaline/Tetraphenylborate Nanospheres and Their
      Application as Ion Selective Electrode for Determination of Clorprenaline in
      Pork.
AB  - A novel modified ion selective electrode based on Fe2O3
      clorprenaline/tetraphenylborate nanospheres (Fe2O3-CLPT NSs) as electroactive
      materials for the determination of clorprenaline hydrochloride (CLP) is
      described. The alpha-Fe2O3 nanoparticles (NPs) were prepared by hydrothermal
      synthesis, then self-assembled on CLP/tetraphenylborate (TPB) to form Fe2O3-CLPT
      NSs, which were used as a potentiometric electrode for analyte determination
      innovatively. The Fe2O3-CLPT NSs modified electrode exhibited a wider
      concentration range from 1.0 * 10(-7) to 1.0 * 10(-1) mol/L and a lower detection
      limit of 3.7 * 10(-8) mol/L compared with unmodified electrodes. The selectivity
      of the modified electrode was evaluated by fixed interference method. The good
      performance of the modified electrode such as wide pH range (2.4-6.7), fast
      response time (15 s), and adequate lifetime (14 weeks) indicate the utility of
      the modified electrode for evaluation of CLP content in various real samples.
      Finally, the modified electrode was successfully employed to detect CLP in pork
      samples with satisfactory results. These results demonstrated the Fe2O3-CLPT NSs
      modified electrode to be a functional and convenient method to the field of
      potentiometry determination of CLP in real samples. 

PMID- 27044308
TI  - Observation of Quantized and Partial Quantized Conductance in Polymer-Suspended
      Graphene Nanoplatelets.
AB  - Quantized conductance is observed at zero magnetic field and room temperature in
      metal-insulator-metal structures with graphene submicron-sized nanoplatelets
      embedded in a 3-hexylthiophene (P3HT) polymer layer. In devices with medium
      concentration of graphene platelets, integer multiples of G o = 2e (2)/h (=12.91
      kOmega(-1)), and in some devices partially quantized including a series of with
      (n/7) * G o, steps are observed. Such an organic memory device exhibits reliable
      memory operation with an on/off ratio of more than 10. We attribute the quantized
      conductance to the existence of a 1-D electron waveguide along the conductive
      path. The partial quantized conductance results likely from imperfect
      transmission coefficient due to impedance mismatch of the first waveguide modes. 

PMID- 27044309
TI  - Validation of the Chinese version of the PHQ-15 in a tertiary hospital.
AB  - BACKGROUND: This study aimed to investigate the reliability and validity of the
      Chinese version of the Patient Health Questionnaire (PHQ-15) in a tertiary
      hospital. METHODS: Using a cross-sectional study design, the Chinese version of
      the PHQ-15 was administered to a total of 1329 inpatients. To examine the
      discriminant validity of this questionnaire, we investigated the correlation of
      the PHQ-15 score with sociodemographic data and the PHQ-9 and GAD-7 scale scores.
      Exploratory factor analysis was performed to assess the internal consistency of
      the PHQ-15. To evaluate the consistency of this questionnaire with item response
      theory (IRT), IRT analysis was performed. RESULTS: The Chinese version of the PHQ
      15 showed good reliability (Cronbach's alpha = 0.83). The correlations of the PHQ
      15 scores with the PHQ-9 depression scale scores (r = 0.565) and the GAD-7
      anxiety scale scores (r = 0.512) were moderate; these results suggested that the
      PHQ-15 had discriminant validity. We identified three factors, referred to as
      "cardiopulmonary," "gastrointestinal," and "pain/neurological," which explained
      56 % of the total variance. A second-order factor analysis including these three
      factors produced an acceptable model. Several items (4, 8 and 11) displayed
      extreme floor effects. Additionally, item 4 displayed a very small variance of
      0.35 and showed very small differences in its thresholds based on IRT analysis.
      CONCLUSIONS: The PHQ-15 scale had good reliability and high validity to detect
      patients with high somatic symptom severity in a Chinese tertiary hospital.
      Several of the current findings were consistent with previous research on the PHQ
      15 in Western countries and in China. To improve the diagnostic quality of this
      questionnaire, items 4, 8 and 11 can be omitted.

PMID- 27044310
TI  - Cardiac Patients' Walking Activity Determined by a Step Counter in Cardiac
      Telerehabilitation: Data From the Intervention Arm of a Randomized Controlled
      Trial.
AB  - BACKGROUND: Walking represents a large part of daily physical activity. It
      reduces both overall and cardiovascular diseases and mortality and is suitable
      for cardiac patients. A step counter measures walking activity and might be a
      motivational tool to increase and maintain physical activity. There is a lack of
      knowledge about both cardiac patients' adherence to step counter use in a cardiac
      telerehabilitation program and how many steps cardiac patients walk up to 1 year
      after a cardiac event. OBJECTIVE: The purpose of this substudy was to explore
      cardiac patients' walking activity. The walking activity was analyzed in relation
      to duration of pedometer use to determine correlations between walking activity,
      demographics, and medical and rehabilitation data. METHODS: A total of 64
      patients from a randomized controlled telerehabilitation trial (Teledi@log) from
      Aalborg University Hospital and Hjoerring Hospital, Denmark, from December 2012
      to March 2014 were included in this study. Inclusion criteria were patients
      hospitalized with acute coronary syndrome, heart failure, and coronary artery
      bypass grafting or valve surgery. In Teledi@log, the patients received
      telerehabilitation technology and selected one of three telerehabilitation
      settings: a call center, a community health care center, or a hospital.
      Monitoring of steps continued for 12 months and a step counter (Fitbit Zip) was
      used to monitor daily steps. RESULTS: Cardiac patients walked a mean 5899 (SD
      3274) steps per day, increasing from mean 5191 (SD 3198) steps per day in the
      first week to mean 7890 (SD 2629) steps per day after 1 year. Adherence to step
      counter use lasted for a mean 160 (SD 100) days. The patients who walked
      significantly more were younger (P=.01) and continued to use the pedometer for a
      longer period (P=.04). Furthermore, less physically active patients weighed more.
      There were no significant differences in mean steps per day for patients in the
      three rehabilitation settings or in the disease groups. CONCLUSIONS: This study
      indicates that cardiac telerehabilitation at a call center can support walking
      activity just as effectively as telerehabilitation at either a hospital or a
      health care center. In this study, the patients tended to walk fewer steps per
      day than cardiac patients in comparable studies, but our study may represent a
      more realistic picture of walking activity due to the continuation of step
      counter use. Qualitative studies on patients' behavior and motivation regarding
      step counter use are needed to shed light on adherence to and motivation to use
      step counters. TRIAL REGISTRATION: ClinicalTrials.gov NCT01752192;
      https://clinicaltrials.gov/ct2/show/NCT01752192 (Archived by WebCite at
      http://www.webcitation.org/6fgigfUyV).

PMID- 27044311
TI  - Affordable care act: comparison of healthcare indicators among different
      insurance beneficiaries with new coverage eligibility.
AB  - BACKGROUND: Health coverage in the United States will be increased to nearly
      universal levels under the Affordable Care Act (ACA). In order to better
      understand the impact of the type of health insurance and health outcomes, there
      is a need to examine health disparities and inequalities between the insured and
      the uninsured based on their eligibility for coverage. METHODS: The current study
      used the data from the Medical Expenditure Panel Survey 2012 (MEPS). Selected
      health characteristics and access to care items were compared in regard to the
      insurance status: private, public, the uninsured, but likely eligible for
      Medicaid expansion (EME), and the uninsured, but likely required to purchase
      health plans through the health insurance exchanges (RPIE). RESULTS: Analyses
      showed that 17.2% of US adults ages 27-64 were eligible as EME and 12.9% as RPIE
      in 2012. Compared to the insured groups, the uninsured who were eligible for
      coverage reported fewer health problems than those insured privately and
      publicly. However, they also reported less use of health care, including
      preventive health service, screenings, and unmet health care needs. CONCLUSIONS:
      The ACA aims to increase coverage options and access to treatment and preventive
      health care services for the majority of the uninsured US population. However, it
      may not play as significant of a role in improving health among the uninsured, in
      particular, those eligible for the Medicaid expansion.

PMID- 27044312
TI  - A novel strain of cynomolgus macaque cytomegalovirus: implications for host-virus
      co-evolution.
AB  - BACKGROUND: Cytomegaloviruses belong to a large, ancient, genus of DNA viruses
      comprised of a wide array of species-specific strains that occur in diverse array
      of hosts. METHODS: In this study we sequenced the ~217 Kb genome of a
      cytomegalovirus isolated from a Mauritius cynomolgus macaque, CyCMV Mauritius,
      and compared it to previously sequenced cytomegaloviruses from a cynomolgus
      macaque of Filipino origin (CyCMV Ottawa) and two from Indian rhesus macaques
      (RhCMV 180.92 and RhCMV 68-1). RESULTS: Though more closely related to CyCMV
      Ottawa, CyCMV Mauritius is less genetically distant from both RhCMV strains than
      is CyCMV Ottawa. Several individual genes, including homologues of CMV genes
      RL11B, UL123, UL83b, UL84 and a homologue of mammalian COX-2, show a closer
      relationship between homologues of CyCMV Mauritius and the RhCMVs than between
      homologues of CyCMV Mauritius and CyCMV Ottawa. A broader phylogenetic analysis
      of 12 CMV strains from eight species recovers evolutionary relationships among
      viral strains that mirror those amongst the host species, further demonstrating
      co-evolution of host and virus. CONCLUSIONS: Phylogenetic analyses of rhesus and
      cynomolgus macaque CMV genome sequences demonstrate co-speciation of the virus
      and host.

PMID- 27044313
TI  - Alkylrhodamines enhance the toxicity of clotrimazole and benzalkonium chloride by
      interfering with yeast pleiotropic ABC-transporters.
AB  - ABC-transporters with broad substrate specificity are responsible for pathogenic
      yeast resistance to antifungal compounds. Here we asked whether highly
      hydrophobic chemicals with delocalized positive charge can be used to overcome
      the resistance. Such molecules efficiently penetrate the plasma membrane and
      accumulate inside the cells. We reasoned that these properties can convert an
      active efflux of the compounds into a futile cycle thus interfering with the
      extrusion of the antibiotics. To test this, we studied the effects of several
      alkylated rhodamines on the drug resistance of yeast Saccharomyces cerevisiae We
      found that octylrhodamine synergetically increases toxicity of Pdr5p substrate
      clotrimazole, while the others were less effective. Next, we compared the
      contributions of three major pleiotropic ABC-transporters (Pdr5p, Yor1p, Snq2p)
      on the accumulation of the alkylated rhodamines. While all of the tested
      compounds were extruded by Pdr5p, Yor1p and Snq2p showed narrower substrate
      specificity. Interestingly, among the tested alkylated rhodamines, inactivation
      of Pdr5p had the strongest effect on the accumulation of octylrhodamine inside
      the cells, which is consistent with the fact that clotrimazole is a substrate of
      Pdr5p. As alkylated rhodamines were shown to be non-toxic on mice, our study
      makes them potential components of pharmacological antifungal compositions.

PMID- 27044314
TI  - Effect of n-3 fatty acids on the expression of inflammatory genes in THP-1
      macrophages.
AB  - BACKGROUND: Uncontrolled inflammation participates in the development of
      inflammatory diseases. Beneficial effects of polyunsaturated fatty acids
      belonging to the n-3 family such as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on inflammation have been reported. The present study
      investigates the basal effects of EPA, DHA and a mixture EPA + DHA on the
      expression of 10 genes (AKT1, MAPK, NFKB, TNFA, IL1Beta, MCP1, ALOX5, PTGS2,
      MGST1 and NOS2) related to inflammation in unstimulated cultured THP1
      macrophages. Cells were incubated for 24 h with n-3 PUFAs (50 MUM and 10 MUM EPA,
      DHA, EPA + DHA). Expression levels of inflammatory genes were analyzed by real
      time PCR. RESULTS: 50 MUM, 10 MUM EPA and 50 MUM EPA + DHA decreased the
      expression of genes involved in the NF-kappaB pathway (MAPK, AKT1, and NFKB).
      Treatment with 50 MUM, 10 MUM EPA, 50 MUM DHA and EPA + DHA decreased expression
      levels of cytokines genes IL1Beta and MCP1. TNFA expression was decreased by 50
      MUM, 10 MUM of EPA, DHA and with 50 MUM EPA + DHA. Two genes involved in the
      fatty acid metabolism (PTGS2 and ALOX5) were also modulated by the n-3 FAs. 50
      MUM of DHA and EPA + DHA inhibited PTGS2 expression when the two concentrations
      of EPA, 50 MUM DHA and EPA + DHA inhibited ALOX5 expression. Finally, the effects
      of n-3 FAs were studied among genes involved in the oxidative stress. 50 MUM of
      each fatty acid increased MGST1 expression. Both concentration of EPA and 50 MUM
      DHA decreased NOS2 expression. CONCLUSION: EPA seems to be more effective than
      DHA and EPA + DHA in modulating expression levels of selected inflammatory genes.
      The concentration of 50 MUM was globally more effective than 10 MUM.

PMID- 27044315
TI  - Depression among people with type 2 diabetes mellitus, US National Health and
      Nutrition Examination Survey (NHANES), 2005-2012.
AB  - BACKGROUND: Depression in people with diabetes can result in increased risk for
      diabetes-related complications. The prevalence of depression has been estimated
      to be 17.6 % in people with type 2 diabetes mellitus (T2DM), based on studies
      published between 1980 and 2005. There is a lack of more recent estimates of
      depression prevalence among the US general T2DM population. METHODS: The present
      study used the US National Health and Nutrition Examination Survey (NHANES) 2005
      2012 data to provide an updated, population-based estimate for the prevalence of
      depression in people with T2DM. NHANES is a cross-sectional survey of a
      nationally representative sample of the civilian, non-institutionalized US
      population. Starting from 2005, the Patient Health Questionnaire (PHQ-9) was
      included to measure signs and symptoms of depression. We defined PHQ-9 total
      scores >= 10 as clinically relevant depression (CRD), and >= 15 as clinically
      significant depression (CSD). Self-reported current antidepressant use was also
      combined to estimate overall burden of depression. Predictors of CRD and CSD were
      investigated using survey logistic regression models. RESULTS: A total of 2182
      participants with T2DM were identified. The overall prevalence of CRD and CSD
      among people with T2DM is 10.6 % (95 % confidence interval (CI) 8.9-12.2 %), and
      4.2 % (95 % CI 3.4-5.1 %), respectively. The combined burden of depressive
      symptoms and antidepressants may be as high as 25.4 % (95 % CI 23.0-27.9 %).
      Significant predictors of CRD include age (younger than 65), sex (women), income
      (lower than 130 % of poverty level), education (below college), smoking (current
      or former smoker), body mass index (>=30 kg/m(2)), sleep problems,
      hospitalization in the past year, and total cholesterol (>=200 mg/dl).
      Significant predictors of CSD also include physical activity (below guideline)
      and cardiovascular diseases. CONCLUSIONS: The prevalence of CRD and CSD among
      people with T2DM in the US may be lower than in earlier studies, however, the
      burden of depression remains high. Further research with longitudinal follow-up
      for depression in people with T2DM is needed to understand real world
      effectiveness of depression management.

PMID- 27044316
TI  - Neurocognitive Deficits and Neurocognitive Rehabilitation in Adult Brain Tumors.
AB  - OPINION STATEMENT: Neurocognitive deficits are common with brain tumors. If
      assessed at presentation using detailed neurocognitive tests, problems are
      detected in 80 % of cases. Neurocognition may be affected by the tumor, its
      treatment, associated medication, mood, fatigue, and insomnia. Interpretation of
      neurocognitive problems should be considered in the context of these factors.
      Early post-operative neurocognitive rehabilitation for brain tumor patients will
      produce rehabilitation outcomes (e.g., quality of life, improved physical
      function, subjective neurocognition) equivalent to stroke, multiple sclerosis,
      and head injury, but the effect size and duration of benefit needs further
      research. In stable patients treated with radiotherapy +/- chemotherapy, the most
      frequent causes of distress include neurocognitive problems, psychological
      factors of anxiety, depression, fatigue, and sleep. Exercise, neurocognitive
      training, neurocognitive behavioral therapy, and medications to treat fatigue,
      behavior, memory, mood, and removal of drugs that may be associated with
      neurocognitive side effects (e.g., anti-epileptic drugs) all show promise in
      helping patients to manage the effects of their neurocognitive impairments
      better. As these are complex symptoms, multidisciplinary expertise is necessary
      to evaluate the influence of each variable to plan appropriate support and
      intervention. Neurocognitive rehabilitation should therefore occur in parallel
      with disease-centered, medical management from the outset. It should not occur in
      series, as a restricted phase in a patient's pathway. It should be considered in
      the pre- and post-operative period where there are good prospects of recovery, as
      one would for any brain-injured patient, so that the person may reach their
      optimal physical, sensory, intellectual, psychological, and social functional
      level. Yet the identification and selection of patients for early neurological
      rehabilitation and routine evaluation of cognition is uncommon in neurosurgical
      wards.

PMID- 27044317
TI  - Hormone-deprived serum impairs angiogenic properties in human endothelial cells
      regardless of estrogens.
AB  - AIMS: In vitro studies on hormone biological activities are commonly performed on
      cells cultured in nominally hormone-free media consisting of phenol-red-free
      media supplemented with charcoal-stripped (CS) serum. These media are largely
      used in almost all cell types, including endothelial cells (ECs). METHODS: Cell
      number and metabolic activity were measured with standard methods. Angiogenesis
      was evaluated in a three-dimensional spheroid sprouting assay. RESULTS: When we
      compared human umbilical vein ECs (HUVECs) cultured in standard conditions (199
      medium supplemented with normal serum) with HUVECs grown in the hormone-free
      medium (phenol-red-free 199 medium supplemented with CS serum), we found that
      cells stop to grow in the absence of hormones. Notably, neither 17-beta2
      estradiol nor dihydrotestosterone reversed this inhibition. Moreover, the
      presence of the CS serum was sufficient to abrogate the ability of HUVECs to
      sprout in a three-dimensional spheroid assay, thus affecting a functional
      property of ECs. CONCLUSIONS: Our results suggest that one or possibly more
      substances removed by stripping procedure from serum and different from sex
      hormones are crucial for the maintenance of in vitro ECs distinctive properties.
      Therefore, caution should be used when ECs are studied in media containing the CS
      serum.

PMID- 27044318
TI  - A novel flapless approach versus minimally invasive surgery in periodontal
      regeneration with enamel matrix derivative proteins: a 24-month randomized
      controlled clinical trial.
AB  - OBJECTIVES: This investigation was designed to compare the effectiveness of
      enamel matrix derivative (EMD) proteins in combination with flapless or flap
      procedure in periodontal regeneration of deep intrabony defects. MATERIALS AND
      METHODS: Thirty chronic periodontitis patients who had at least one residual
      periodontal defect with an intrabony component of >=3 mm were consecutively
      enrolled. Defects were randomly assigned to test or control treatments which both
      consisted of the use of EMD to reach periodontal regeneration. Test sites (n =
      15) were treated according to a novel flapless approach, whereas control sites (n
      = 15) by means of minimally invasive surgery (MIST). Clinical and radiographic
      parameters were recorded at baseline, 12 and 24 months post-operatively. RESULTS:
      Both therapeutic modalities yielded similar probing depth (PD) reduction and
      clinical attachment level (CAL) gain at 24 months. In flapless-treated sites, a
      mean PD reduction of 3.6 +/- 1.0 mm and a CAL gain of 3.2 +/- 1.1 mm were
      observed. In the MIST group, they were 3.7 +/- 0.6 and 3.6 +/- 0.9 mm. The
      operative chair time was twice as long in the MIST compared to the flapless
      group, whereas comparable patient-oriented outcomes were observed. CONCLUSION:
      The flapless procedure may be successfully applied in the regenerative treatment
      of deep intrabony defects reaching clinical outcomes comparable with those of
      minimally invasive surgical approaches and may present important advantages in
      terms of reduction of operative chair time. CLINICAL RELEVANCE: The use of EMD as
      an adjunct to non-surgical periodontal treatment may be considered a suitable
      option to treat defects mainly in the anterior sextants.

PMID- 27044319
TI  - Recognizing the Presidents: Was Alexander Hamilton President?
AB  - Studies over the past 40 years have shown that Americans can recall about half
      the U.S. presidents. Do people know the presidents even though they are unable to
      access them for recall? We investigated this question using the powerful cues of
      a recognition test. Specifically, we tested the ability of 326 online subjects to
      recognize U.S. presidents when presented with their full names among various
      types of lures. The hit rate for presidential recognition was .88, well above the
      proportion produced in free recall but far from perfect. Presidents Franklin
      Pierce and Chester Arthur were recognized less than 60% of the time.
      Interestingly, four nonpresidents were falsely recognized at relatively high
      rates, and Alexander Hamilton was more frequently identified as president than
      were several actual presidents. Even on a recognition test, knowledge of American
      presidents is imperfect and prone to error. The false alarm data support the
      theory that false fame can arise from contextual familiarity.

PMID- 27044320
TI  - The role of RNA editing by ADAR1 in prevention of innate immune sensing of self
      RNA.
AB  - The innate immune system is the first line of the cellular defence against
      invading pathogens. A critical component of this defence is the capacity to
      discriminate foreign RNA molecules, which are distinct from most cellular RNAs in
      structure and/or modifications. However, a series of rare
      autoimmune/autoinflammatory diseases in humans highlight the propensity for the
      innate immune sensing system to be activated by endogenous cellular double
      stranded RNAs (dsRNAs), underscoring the fine line between distinguishing self
      from non-self. The RNA editing enzyme ADAR1 has recently emerged as a key
      regulator that prevents innate immune pathway activation, principally the
      cytosolic dsRNA sensor MDA5, from inducing interferon in response to double
      stranded RNA structures within endogenous RNAs. Adenosine-to-Inosine RNA editing
      by ADAR1 is proposed to destabilise duplexes formed from inverted repetitive
      elements within RNAs, which appear to prevent MDA5 from sensing these RNA as
      virus-like in the cytoplasm. Aberrant activation of these pathways has
      catastrophic effects at both a cellular and organismal level, contributing to one
      of the causes of the conditions collectively known as the type I
      interferonopathies.

PMID- 27044321
TI  - Seasonal heterogeneity of ocean warming: a mortality sink for ectotherm
      colonizers.
AB  - Distribution shifts are a common adaptive response of marine ectotherms to
      climate change but the pace of redistribution depends on species-specific traits
      that may promote or hamper expansion to northern habitats. Here we show that
      recently, the loggerhead turtle (Caretta caretta) has begun to nest steadily
      beyond the northern edge of the species' range in the Mediterranean basin. This
      range expansion is associated with a significant warming of spring and summer sea
      surface temperature (SST) that offers a wider thermal window suitable for
      nesting. However, we found that post-hatchlings departing from this location
      experience low winter SST that may affect their survival and thus hamper the
      stabilization of the site by self-recruitment. The inspection of the
      Intergovernmental Panel on Climate Change model projections and observational
      data on SST trends shows that, despite the annual warming for this century,
      winter SST show little or no trends. Therefore, thermal constraints during the
      early developmental phase may limit the chance of population growth at this
      location also in the near future, despite increasingly favourable conditions at
      the nesting sites. Quantifying and understanding the interplay between dispersal
      and environmental changes at all life stages is critical for predicting ectotherm
      range expansion with climate warming. 

PMID- 27044323
TI  - Feliform carnivores have a distinguished constitutive innate immune response.
AB  - Determining the immunological phenotype of endangered and threatened populations
      is important to identify those vulnerable to novel pathogens. Among mammals,
      members of the order Carnivora are particularly threatened by diseases. We
      therefore examined the constitutive innate immune system, the first line of
      protection against invading microbes, of six free-ranging carnivore species; the
      black-backed jackal (Canis mesomelas), the brown hyena (Hyena brunnea), the
      caracal (Caracal caracal), the cheetah (Acinonyx jubatus), the leopard (Panthera
      pardus) and the lion (Panthera leo) using a bacterial killing assay. The
      differences in immune responses amongst the six species were independent of their
      foraging behaviour, body mass or social organisation but reflected their
      phylogenetic relatedness. The bacterial killing capacity of black-backed jackals,
      a member of the suborder Caniformia, followed the pattern established for a wide
      variety of vertebrates. In contrast, the five representatives of the suborder
      Feliformia demonstrated a killing capacity at least an order of magnitude higher
      than any species reported previously, with a particularly high capacity in
      caracals and cheetahs. Our results suggest that the immunocompetence of
      threatened felids such as the cheetah has been underestimated and its assessment
      ought to consider both innate and adaptive components of the immune system. 

PMID- 27044324
TI  - Trim37-deficient mice recapitulate several features of the multi-organ disorder
      Mulibrey nanism.
AB  - Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder
      characterized by severe prenatal-onset growth failure, infertility, cardiopathy,
      risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of
      function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to
      the tripartite motif (TRIM) protein family and having both peroxisomal and
      nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-))
      model for MUL. Trim37(-/-) mice were viable and had normal weight development
      until approximately 12 months of age, after which they started to manifest
      increasing problems in wellbeing and weight loss. Assessment of skeletal
      parameters with computer tomography revealed significantly smaller skull size,
      but no difference in the lengths of long bones in Trim37(-/-) mice as compared
      with wild-type. Both male and female Trim37(-/-) mice were infertile, the gonads
      showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of
      lipids in and around Leydig cells. Male Trim37(-/-) mice had elevated levels of
      follicle-stimulating and luteinizing hormones, but maintained normal levels of
      testosterone. Six-month-old Trim37(-/-) mice had elevated fasting blood glucose
      and low fasting serum insulin levels. At 1.5 years Trim37(-/-) mice showed non
      compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The
      amount and morphology of liver peroxisomes seemed normal in Trim37(-/-) mice. The
      most consistently seen phenotypes in Trim37(-/-) mice were infertility and the
      associated hormonal findings, whereas there was more variability in the other
      phenotypes observed. Trim37(-/-) mice recapitulate several features of the human
      MUL disease and thus provide a good model to study disease pathogenesis related
      to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease,
      cardiomyopathy and tumorigenesis. 

PMID- 27044325
TI  - VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and
      proteolysis.
AB  - Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine
      kinase VEGFR2 triggers multiple signal transduction pathways, which regulate
      endothelial cell responses that control vascular development. Multiple isoforms
      of VEGF-A can elicit differential signal transduction and endothelial responses.
      However, it is unclear how such cellular responses are controlled by isoform
      specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the
      membrane trafficking of receptor-ligand complexes influences signal transduction
      and protein turnover. By building on these concepts, our study shows for the
      first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF
      A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early
      endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF
      A isoform-specific signal transduction events. Disruption of clathrin-dependent
      endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal
      transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2
      levels. Furthermore, such VEGF-A isoforms promoted differential patterns of
      VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now
      provides novel insights into how different VEGF-A isoforms can bind the same
      receptor tyrosine kinase and elicit diverse cellular outcomes. 

PMID- 27044326
TI  - Randomised trial of once-daily vilanterol in children with asthma on inhaled
      corticosteroid therapy.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are effective maintenance treatments
      for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI)
      is an inhaled long-acting beta-2 agonist which, in combination with the ICS
      fluticasone furoate, is being explored as a once-daily treatment for asthma in
      children. We evaluated the dose-response, efficacy, and safety of once-daily VI
      (6.25 MUg, 12.5 MUg and 25 MUg) administered in the evening over 4 weeks, on
      background fluticasone propionate (FP) in children with asthma inadequately
      controlled on ICS. METHODS: This was a Phase IIb, multicentre, randomised, double
      blind, parallel-group, placebo-controlled study in children ages 5-11 years with
      persistent asthma on ICS and as-needed short-acting beta-agonist. The study
      comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From
      study start, children replaced their current ICS with open-label FP 100 MUg twice
      daily. Children were randomised to receive placebo, VI 6.25 MUg, VI 12.5 MUg or
      VI 25 MUg once daily. Primary endpoint was treatment difference between VI 25 and
      placebo groups in mean change from baseline in evening peak expiratory flow
      averaged over the 4-week treatment. Secondary endpoints included change from
      baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and
      change from baseline in percentage of rescue-free and symptom-free 24-h periods.
      Safety assessments included incidence of adverse events (AEs) and asthma
      exacerbations. RESULTS: In total, 456 children comprised the intention-to-treat
      population. The adjusted treatment difference between VI 25 and placebo groups
      for the primary endpoint was not statistically significant (p = 0.227) so no
      statistical inference was made for other VI dose comparisons or other endpoints.
      No difference in change from baseline in trough FEV1 was observed for any VI
      treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue
      free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs
      was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine
      children experienced asthma exacerbations during the treatment period.
      CONCLUSION: VI plus FP did not result in significant improvements in lung
      function versus placebo plus FP, but was well tolerated at all doses assessed.
      TRIAL REGISTRATION: NCT01573767 (ClinicalTrials.gov).

PMID- 27044327
TI  - Hypothesis testing for differentially correlated features.
AB  - In a multivariate setting, we consider the task of identifying features whose
      correlations with the other features differ across conditions. Such correlation
      shifts may occur independently of mean shifts, or differences in the means of the
      individual features across conditions. Previous approaches for detecting
      correlation shifts consider features simultaneously, by computing a correlation
      based test statistic for each feature. However, since correlations involve two
      features, such approaches do not lend themselves to identifying which feature is
      the culprit. In this article, we instead consider a serial testing approach, by
      comparing columns of the sample correlation matrix across two conditions, and
      removing one feature at a time. Our method provides a novel perspective and
      favorable empirical results compared with competing approaches.

PMID- 27044328
TI  - BET Bromodomain Suppression Inhibits VEGF-induced Angiogenesis and Vascular
      Permeability by Blocking VEGFR2-mediated Activation of PAK1 and eNOS.
AB  - The tyrosine kinase receptor vascular endothelial growth factor receptor 2
      (VEGFR2) is a critical modulator of angiogenesis. Increasing evidence indicate
      the important role of bromodomain and extra-terminal domain (BET) of chromatin
      adaptors in regulating tumor growth and inflammatory response. However, whether
      BET proteins have a role in angiogenesis and endothelial permeability is unclear.
      In this study, we observed that treatment with JQ1, a specific BET inhibitor,
      suppressed in vitro tube formation of human umbilical vein endothelial cells
      (HUVECs) and in vivo angiogenesis in a Matrigel plug and oxygen-induced
      retinopathy neovascularization. JQ1 attenuated the VEGF-induced decrease in TEER
      in HUVECs and prevented Evans blue dye leakage in the VEGF-induced Miles assay in
      athymic Balb/c nude mice. BET inhibition with JQ1 or shRNA for Brd2 or Brd4
      suppressed VEGF-induced migration, proliferation, and stress fiber formation of
      HUVECs. Furthermore, BET inhibition suppressed phosphorylation of VEGFR2 and
      PAK1, as well as eNOS activation in VEGF-stimulated HUVECs. Inhibition with
      VEGFR2 and PAK1 also reduced migration and proliferation, and attenuated the VEGF
      induced decrease in TEER. Thus, our observations suggest the important role of
      BET bromodomain in regulating VEGF-induced angiogenesis. Strategies that target
      the BET bromodomain may provide a new therapeutic approach for angiogenesis
      related diseases. 

PMID- 27044329
TI  - Molecular cloning, characterization, and expression analysis of p53 from the
      oriental river prawn, Macrobrachium nipponense, in response to hypoxia.
AB  - The tumor suppressor gene p53 plays a critical role in safeguarding the integrity
      of the genome in mammalian cells. It acts as a sequence-specific transcription
      factor. Once p53 is activated by a variety of cellular stresses, it
      transactivates downstream target genes and regulates the cell cycle and
      apoptosis. However, little is known about the functions of the p53 pathway in
      prawns in response to hypoxia. In this study, the cDNA of p53 from the oriental
      river prawn, Macrobrachium nipponense, (Mnp53) was cloned using a combination of
      homology cloning and rapid amplification of cDNA ends. The full-length cDNA of
      Mnp53 has 2130 bp, including an open reading frame of 1125 bp that encodes a
      polypeptide of 374 amino acids with a predicted molecular weight of 41.9 kDa and
      a theoretical isoelectric point of 6.9. Quantitative real-time (qRT)-PCR assays
      revealed that Mnp53 was ubiquitously expressed in all examined tissues, but at
      high levels in the hepatopancreas. In addition, we studied respiratory bursts and
      reactive oxygen species (ROS) production in the hepatopancreas of M. nipponense.
      Our results suggest that oxidative stress occurred in prawns in response to
      hypoxia and that apoptosis was associated with an increase in caspase-3 mRNA
      expression. qRT-PCR and western blot results confirmed that hypoxic stress
      induced the upregulation of Mnp53 at mRNA and protein levels. Furthermore,
      immunohistochemistry showed remarkable changes in immunopositive staining after
      the same hypoxic treatment. These results suggest that hypoxia-induced oxidative
      stress may cause apoptosis and cooperatively stimulate the expression of Mnp53. 

PMID- 27044330
TI  - sIgZ exhibited maternal transmission in embryonic development and played a
      prominent role in mucosal immune response of Megalabrama amblycephala.
AB  - IgZ is considered to be the last immunoglobulin discovered in vertebrate species.
      In this study, the structure of secreted form of blunt snout bream (Megalabrama
      amblycephala) IgZ (sIgZ) heavy chain gene is VH-Czeta1-Czeta2-Czeta3-Czeta4, in
      which Czeta4 provides the specificity to the IgZ isotype. The deduced amino acid
      sequence of sIgZ shows highest similarity with that of Ctenopharyngodon idella
      (79%). The ontogeny of sIgZ gene expression showed a V-shape change pattern:
      decreased initially from unfertilized egg stage to 16-cell embryos and increased
      significantly from blastula stage, which exhibited maternal transmission effects.
      Compared with the juvenile fish, sIgZ mRNA level was higher in head kidney,
      spleen, trunk kidney, liver, intestine and gill of adult fish. In both juvenile
      and adult fish, sIgZ mRNA was detected in intestine and gill. Aeromonas
      hydrophila challenge experiment showed that sIgZ transcription significantly
      increased in skin, gill and intestine, indicating a prominent mucosal immune
      response. The results of Western blot also verified the protein alterations of
      sIgZ in mucosal organs in M. amblycephal. Our studies indicate a prominent role
      of IgZ in mucosa-associated lymphoid tissue immunity and further support the
      specialized role of IgZ in teleost mucosal immune responses. 

PMID- 27044331
TI  - Molecular immune response of channel catfish immunized with live theronts of
      Ichthyophthirius multifiliis.
AB  - The parasite Ichthyophthirius multifiliis (Ich) has been reported in various
      freshwater fishes worldwide and results in severe losses to both food and
      aquarium fish production. The fish surviving natural infections or immunized with
      live theronts develop strong specific and non-specific immune responses. Little
      is known about how these immune genes are induced or how they interact and lead
      to specific immunity against Ichthyophthirius multifiliis in channel catfish
      Ictalurus punctatus. This study evaluated the differential expression of immune
      related genes, including immunoglobulin, immune cell receptor, cytokine,
      complement factor and toll-like receptors in head kidney from channel catfish at
      different time points after immunization with live theronts of I. multifiliis.
      The immunized fish showed significantly higher anti-Ich antibody expressed as
      immobilization titer and ELISA titer than those of control fish. The vast
      majority of immunized fish (95%) survived theront challenge. Expression of IgM
      and IgD heavy chain genes exhibited a rapid increase from 4 hour (h4) to 2 days
      (d2) post immunization. Expression of immune cell receptor genes (CD4, CD8-alpha,
      MHC I, MHC II beta, TcR-alpha, and TcR-beta) showed up-regulation from h4 to d6
      post immunization, indicating that different immune cells were actively involved
      in cellular immune response. Cytokine gene expression (IL-1betaa, IL-1betab, IFN
      gamma and TNF-alpha) increased rapidly at h4 post immunization and were at an up
      regulated level until d2 compared to the bovine serum albumin control. Expression
      of complement factor and toll-like receptor genes exhibited a rapid increase from
      h4 to d2 post immunization. Results of this study demonstrated differential
      expression of genes involved in the specific or non-specific immune response post
      immunization and that the vaccination against Ich resulted in protection against
      infection by I. multifiliis. 

PMID- 27044332
TI  - Rationale and design of a randomized trial to test the safety and non-inferiority
      of canagliflozin in patients with diabetes with chronic heart failure: the CANDLE
      trial.
AB  - BACKGROUND: Because type 2 diabetes mellitus is associated strongly with an
      increased risk of cardiovascular diseases, the number of patients with diabetes
      with chronic heart failure is increasing steadily. However, clinical evidence of
      therapeutic strategies in such patients is still lacking. A recent randomized,
      placebo-controlled trial in patients with type 2 diabetes with high
      cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced
      the incidence of hospitalization for heart failure. Because SGLT2 inhibitors
      cause a reduction in body weight and blood pressure in addition to improving
      glycemic control, they have the potential to exert beneficial effects on the
      clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is
      to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor,
      compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes
      mellitus and chronic heart failure. METHODS: A total of 250 patients with type 2
      diabetes who are drug-naive or taking any anti-diabetic agents and suffering from
      chronic heart failure with a New York Heart Association classification I to III
      will be randomized centrally into either canagliflozin or glimepiride groups (1:
      1) using the dynamic allocation method stratified by age (<65, >=65 year), HbA1c
      level (<6.5, >=6.5 %), and left ventricular ejection fraction (<40, >=40 %).
      After randomization, all the participants will be given the add-on study drug for
      24 weeks in addition to their background therapy. The primary endpoint is the
      percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key
      secondary endpoints after 24 weeks of treatment are the change from baseline in
      glycemic control, blood pressure, body weight, lipid profile, quality of life
      score related to heart failure, and cardiac and renal function. DISCUSSION: The
      CANDLE trial is the first to assess the safety and non-inferiority of
      canagliflozin in comparison with glimepiride in patients with type 2 diabetes
      with chronic heart failure. This trial has the potential to evaluate the clinical
      safety and efficacy of canagliflozin on heart failure. Trial registration Unique
      trial Number, UMIN000017669.

PMID- 27044333
TI  - Short peptide based nanotubes capable of effective curcumin delivery for treating
      drug resistant malaria.
AB  - BACKGROUND: Curcumin (Ccm) has shown immense potential as an antimalarial agent;
      however its low solubility and less bioavailability attenuate the in vivo
      efficacy of this potent compound. In order to increase Ccm's bioavailability, a
      number of organic/inorganic polymer based nanoparticles have been investigated.
      However, most of the present day nano based delivery systems pose a conundrum
      with respect to their complex synthesis procedures, poor in vivo stability and
      toxicity issues. Peptides due to their high biocompatibility could act as
      excellent materials for the synthesis of nanoparticulate drug delivery systems.
      Here, we have investigated dehydrophenylalanine (DeltaPhe) di-peptide based self
      assembled nanoparticles for the efficient delivery of Ccm as an antimalarial
      agent. The self-assembly and curcumin loading capacity of different DeltaPhe
      dipeptides, phenylalanine-alpha,beta-dehydrophenylalanine (FDeltaF), arginine
      alpha,beta-dehydrophenylalanine (RDeltaF), valine-alpha,beta-dehydrophenylalanine
      (VDeltaF) and methonine-alpha,beta-dehydrophenylalanine (MDeltaF) were
      investigated for achieving enhanced and effective delivery of the compound for
      potential anti-malarial therapy. RESULTS: FDeltaF, RDeltaF, VDeltaF and MDeltaF
      peptides formed different types of nanoparticles like nanotubes and nanovesicles
      under similar assembling conditions. Out of these, F?F nanotubes showed maximum
      curcumin loading capacity of almost 68 % W/W. Ccm loaded F?F nanotubes (Ccm-F?F)
      showed comparatively higher (IC50, 3.0 uM) inhibition of Plasmodium falciparum
      (Indo strain) as compared to free Ccm (IC50, 13 uM). Ccm-F?F nano formulation
      further demonstrated higher inhibition of parasite growth in malaria infected
      mice as compared to free Ccm. The dipeptide nanoparticles were highly
      biocompatible and didn't show any toxic effect on mammalian cell lines and normal
      blood cells. CONCLUSION: This work provides a proof of principle of using highly
      biocompatible short peptide based nanoparticles for entrapment and in vivo
      delivery of Ccm leading to an enhancement in its efficacy as an antimalarial
      agent.

PMID- 27044334
TI  - Toll like receptor 9 antagonism modulates spinal cord neuronal function and
      survival: Direct versus astrocyte-mediated mechanisms.
AB  - Toll like receptors (TLRs) are expressed by cells of the immune system and
      mediate the host innate immune responses to pathogens. However, increasing
      evidence indicates that they are important contributors to central nervous system
      (CNS) function in health and in pathological conditions involving sterile
      inflammation. In agreement with this idea, we have previously shown that
      intrathecal administration of a TLR9 antagonist, cytidine-phosphate-guanosine
      oligodeoxynucleotide 2088 (CpG ODN 2088), ameliorates the outcomes of spinal cord
      injury (SCI). Although these earlier studies showed a marked effect of CpG ODN
      2088 on inflammatory cells, the expression of TLR9 in spinal cord (SC) neurons
      and astrocytes suggested that the antagonist exerts additional effects through
      direct actions on these cells. The current study was undertaken to assess the
      direct effects of CpG ODN 2088 on SC neurons, astrocytes and astrocyte-neuron
      interactions, in vitro. We report, for the first time, that inhibition of TLR9 in
      cultured SC neurons alters their function and confers protection against kainic
      acid (KA)-induced excitotoxic death. Moreover, the TLR9 antagonist attenuated the
      KA-elicited endoplasmic reticulum (ER) stress response in neurons, in vitro. CpG
      ODN 2088 also reduced the transcript levels and release of chemokine (C-X-C)
      motif ligand 1 (CXCL1) and monocyte chemotactic protein 1 (MCP-1) by astrocytes
      and it diminished interleukin-6 (IL-6) release without affecting transcript
      levels in vitro. Conditioned medium (CM) of CpG ODN 2088-treated astroglial
      cultures decreased the viability of SC neurons compared to CM of vehicle-treated
      astrocytes. However, this toxicity was not observed when astrocytes were co
      cultured with neurons. Although CpG ODN 2088 limited the survival-promoting
      effects of astroglia, it did not reduce neuronal viability compared to controls
      grown in the absence of astrocytes. We conclude that the TLR9 antagonist acts
      directly on both SC neurons and astrocytes. Neuronal TLR9 antagonism confers
      protection against excitotoxic death. It is likely that this neuroprotection is
      partly due to the attenuation of the ER stress response provoked by
      excitotoxicity. Although CpG ODN 2088 limits the supportive effects of astrocytes
      on neurons, it could potentially exert beneficial effects by decreasing the
      release of pro-inflammatory cytokines and chemokines by astroglia. These findings
      highlight the multiple roles of TLR9 in the SC and have implications for
      pathological conditions including SCI where excitotoxicity and neuroinflammation
      play a prominent role in neuronal degeneration. 

PMID- 27044335
TI  - Systemic TAK-242 prevents intrathecal LPS evoked hyperalgesia in male, but not
      female mice and prevents delayed allodynia following intraplantar formalin in
      both male and female mice: The role of TLR4 in the evolution of a persistent pain
      state.
AB  - OBJECTIVE: Pain resulting from local tissue injury or inflammation typically
      resolves with time. Frequently, however, this pain may unexpectedly persist,
      becoming a pathological chronic state. Increasingly, the innate and adaptive
      immune systems are being implicated in the initiation and maintenance of these
      persistent conditions. In particular, Toll-like receptor 4 (TLR4) signaling has
      been shown to mediate the transition to a persistent pain state in a sex
      dependent manner. In the present work, we explored this contribution using the
      TLR4 antagonist, TAK-242. METHODS: Male and female C57Bl/6 mice were given
      intravenous (IV), intrathecal (IT), or intraperitoneal (IP) TAK-242 prior to IT
      delivery of lipopolysaccharide (LPS), and tactile reactivity was assessed at
      regular intervals over 72-h. Additional groups of mice were treated with IP TAK
      242 prior to intraplantar formalin, and flinching was monitored for 1-h. Tactile
      reactivity was assessed at 7-days after formalin delivery. RESULTS: LPS evoked
      TNF release from male and female macrophages and RAW267.4 cells, which was
      blocked in a concentration dependent fashion by TAK-242. In vivo, IT LPS evoked
      tactile allodynia to a greater degree in male than female mice. TAK-242, given by
      all routes, prevented development of IT LPS-induced tactile allodynia in male
      animals, but did not reverse their established allodynia. TLR4 deficiency and TAK
      242 treatment attenuated IT LPS-induced allodynia in male, but not female mice.
      In the formalin model, pre-treatment with TAK-242 did not affect Phase 1 or Phase
      2 flinching, but prevented the delayed tactile allodynia in both male and
      unexpectedly in female mice (Phase 3). CONCLUSIONS: Together, these results
      suggest that TAK-242 is a TLR4 antagonist that has efficacy after systemic and
      intrathecal delivery and confirms the role of endogenous TLR4 signaling in
      triggering the development of a delayed allodynia in both male and female mice.

PMID- 27044336
TI  - Distinguishing commercially grown Ganoderma lucidum from Ganoderma lingzhi from
      Europe and East Asia on the basis of morphology, molecular phylogeny, and
      triterpenic acid profiles.
AB  - In China and other countries of East Asia, so-called Ling-zhi or Reishi mushrooms
      are used in traditional medicine since several centuries. Although the common
      practice to apply the originally European name 'Ganoderma lucidum' to these fungi
      has been questioned by several taxonomists, this is still generally done in
      recent publications and with commercially cultivated strains. In the present
      study, two commercially sold strains of 'G. lucidum', M9720 and M9724 from the
      company Mycelia bvba (Belgium), are compared for their fruiting body
      (basidiocarp) morphology combined with molecular phylogenetic analyses, and for
      their secondary metabolite profile employing an ultra-performance liquid
      chromatography-electrospray ionization mass spectrometry (UPLC-ESIMS) in
      combination with a high resolution electrospray ionization mass spectrometry (HR
      ESI-MS). According to basidiocarp morphology, the strain M9720 was identified as
      G. lucidum s.str. whereas M9724 was determined as Ganoderma lingzhi. In molecular
      phylogenetic analyses, the M9720 ITS and beta-tubulin sequences grouped with
      sequences of G. lucidum s.str. from Europe whereas those from M9724 clustered
      with sequences of G. lingzhi from East Asia. We show that an ethanol extract of
      ground basidiocarps from G. lucidum (M9720) contains much less triterpenic acids
      than found in the extract of G. lingzhi (M9724). The high amount of triterpenic
      acids accounts for the bitter taste of the basidiocarps of G. lingzhi (M9724) and
      of its ethanol extract. Apparently, triterpenic acids of G. lucidum s.str. are
      analyzed here for the first time. These results demonstrate the importance of
      taxonomy for commercial use of fungi. 

PMID- 27044337
TI  - Relational Issues Within Couples Coping With Parkinson's Disease: Implications
      and Ideas for Family-Focused Care.
AB  - The ways in which Parkinson's disease (PD) impacts, and is experienced by, the
      couple (i.e., the individual with PD and his or her spouse or other romantic
      partner) have not been fully elucidated. Such research is strongly warranted
      because when one member of a couple is chronically ill, it can cause major
      distress for not only the patient but also for his or her partner and their
      relationship. Therefore, the goal of this study was to examine how PD affects a
      couple's relationship. Data from 44 individual, in-depth interviews (with 21
      persons with PD and 23 partners) revealed several challenges that PD commonly
      invokes in the patient-partner relationship, though most participants reported
      that PD had not decreased their overall relational closeness. The findings have
      significant practical implications for family-focused care.

PMID- 27044338
TI  - Recent trends in life expectancy for people with type 1 diabetes in Sweden.
AB  - AIMS/HYPOTHESIS: People with type 1 diabetes have reduced life expectancy (LE)
      compared with the general population. Our aim is to quantify mortality changes
      from 2002 to 2011 in people with type 1 diabetes in Sweden. METHODS: This study
      uses health records from the Swedish National Diabetes Register (NDR) linked with
      death records. Abridged period life tables for those with type 1 diabetes aged 20
      years and older were derived for 2002-06 and 2007-11 using Chiang's method. Cox
      proportional hazard models were used to assess trends in overall and cause
      specific mortality. RESULTS: There were 27,841 persons aged 20 years and older
      identified in the NDR as living with type 1 diabetes between 2002 and 2011,
      contributing 194,685 person-years of follow-up and 2,018 deaths. For men with
      type 1 diabetes, the remaining LE at age 20 increased significantly from 47.7
      (95% CI 46.6, 48.9) in 2002-06 to 49.7 years (95% CI 48.9, 50.6) in 2007-11. For
      women with type 1 diabetes there was no significant change, with an LE at age 20
      of 51.7 years (95% CI 50.3, 53.2) in 2002-06 and 51.9 years (95% CI 50.9, 52.9)
      in 2007-11. Cardiovascular mortality significantly reduced, with a per year HR of
      0.947 (95% CI 0.917, 0.978) for men and 0.952 (95% CI 0.916, 0.989) for women.
      CONCLUSIONS/INTERPRETATION: From 2002-06 to 2007-11 the LE at age 20 of Swedes
      with type 1 diabetes increased by approximately 2 years for men but minimally for
      women. These recent gains have been driven by reduced cardiovascular mortality.

PMID- 27044339
TI  - Gaps in life expectancy for people with type 1 diabetes.
AB  - Two papers in this issue of Diabetologia present recent trends in life expectancy
      for people with type 1 diabetes, one using data from an Australian registry (Huo
      et al, DOI: 10.1007/s00125-015-3857-4 ), the other, a Swedish registry (Petrie et
      al, DOI: 10.1007/s00125-016-3914-7 ). This commentary provides a brief review of
      the concept of the period life expectancy and complexities regarding
      applicability to patients, before summarising and discussing the main results of
      the two papers. In addition, some remaining relevant knowledge gaps are
      discussed.

PMID- 27044340
TI  - Effects of an icon-based menu labelling initiative on consumer food choice.
AB  - AIMS: The purpose of this study was to examine the impact of an icon-based menu
      labelling initiative on consumer buying behaviour. METHODS: This quasi
      experimental study recruited a convenience sample of eight food service
      establishments, all with at least one menu item meeting the heart healthy
      criteria. Data from sales of all menu items sold over an 8-week period were
      collated 4 weeks prior to and 4 weeks during the display of information icons
      related to healthy food choices on menus. RESULTS: The absolute change in menu
      item sales showed a non-significant trend towards an increase in healthier menu
      item selections. Furthermore, there was no association between the type of food
      service establishment and the percentage change in labelled menu item sales.
      CONCLUSION: The study did not find a statistically significant influence of the
      icon-based menu labels on consumer food choice. Given the limited amount of
      research that examines alternative menu labelling formats in real-world settings,
      more studies are necessary to confirm these results. Further research is needed
      to identify the optimal format, content and impact of menu labels on consumer
      behaviour.

PMID- 27044341
TI  - Drusen volume development over time and its relevance to the course of age
      related macular degeneration.
AB  - AIMS: To quantify the change in drusen volume over time and identify its
      prognostic value for individual risk assessment. METHODS: A prospective
      observational study over a minimum of 3 years and maximum of 5 years and follow
      up examination every 3 months was conducted at the ophthalmology department of
      the Medical University of Vienna. 109 patients presenting early and intermediate
      age-related macular degeneration (AMD) were included, of which 30 patients
      concluded a regular follow-up for at least 3 years. 50 eyes of 30 patients were
      imaged every 3 months using spectral-domain and polarisation-sensitive optical
      coherence tomography (OCT). Drusen volume was measured using an automated
      algorithm. Data of a 6-month follow-up were segmented manually by expert graders.
      RESULTS: Gradings from 24 000 individual B-scans showed solid correlation between
      manual and automated segmentation with an initial mean drusen volume of 0.17 mm3.
      The increase in drusen volume was shown to be comparable among all eyes, and a
      model for long-term drusen volume development could be fitted as a cubic
      polynomial function and an R2=0.955. Spontaneous drusen regression was observed
      in 22 of 50 eyes. In this group, four eyes developed choroidal neovascularisation
      and three geographic atrophy. CONCLUSIONS: Drusen volume increase over time can
      be described by a cubic function. Spontaneous regression appears to precede
      conversion to advanced AMD. OCT might be a promising tool for predicting the
      individual risk of progression of AMD.

PMID- 27044342
TI  - Associations between obstructive sleep apnoea, primary open angle glaucoma and
      age-related macular degeneration: record linkage study.
AB  - BACKGROUND: Primary open angle glaucoma (POAG) is thought to be associated with
      obstructive sleep apnoea (OSA) but previous studies are conflicting and have
      methodological limitations. This potential relationship has implications for
      investigation and treatment strategies, and may provide insights into disease
      pathogenesis. The relationship between OSA and age-related macular degeneration
      (AMD) is unknown. METHODS: A sleep apnoea cohort of 67 786 people was constructed
      from linked English hospital episode statistics (1999-2011). We compared this
      cohort with a reference cohort (2 684 131 people) for rates of subsequent POAG
      and AMD. A POAG cohort (comprising 87 435 people) and an AMD cohort (248 408
      people) were also constructed and compared with the reference cohort for rates of
      subsequent sleep apnoea. All analyses were restricted to people aged 55 and over
      and, within this age range, were age standardised using 5-year age groups.
      RESULTS: Risk of POAG following sleep apnoea was not elevated: the rate ratio for
      POAG was 1.01 (95% CI 0.85 to 1.19). Similarly, the risk of sleep apnoea
      following POAG was not elevated: the rate ratio was 1.00 (0.86 to 1.17). These
      findings held true across subgroup analysis according to sex and age group. By
      contrast, the risk of AMD following sleep apnoea was significantly elevated, with
      rate ratio 1.44 (1.32 to 1.57). CONCLUSIONS: Although plausible mechanisms exist
      to consider a link between OSA and POAG, the two conditions are not positively
      associated. This holds true in either temporal direction. By contrast, OSA is
      positively associated with AMD. While potential confounding factors may
      contribute, obesity does not appear sufficient to explain this association.

PMID- 27044343
TI  - Pectin extraction from pomegranate peels with citric acid.
AB  - Pectins were extracted from pomegranate peels with citric acid, according to a
      central composite design with three variables: pH (2-4), temperature (70-90
      degrees C), and extraction time (40-150min). Fourier transform infrared (FTIR)
      spectroscopy was used to follow changes in material composition during the main
      steps of pectin extraction, and also to determine the degree of methyl
      esterification and galacturonic acid content of pectins produced under different
      conditions. Harsh conditions enhanced the extraction yield and the galacturonic
      acid contents, but decreased the degree of methoxylation. The optimum extraction
      conditions, defined as those predicted to result in a yield of galacturonic acid
      higher than 8g/100g while keeping a minimum degree of methoxylation of 54% were:
      88 degrees C, 120min, pH 2.5. Close agreement was found between experimental and
      predicted values at the extraction conditions defined as optimum. 

PMID- 27044344
TI  - Structural and thermodynamic properties of kappa class glutathione transferase
      from Camelus dromedarius.
AB  - The Arabian camel, Camelus dromedarius is naturally adapted to extreme desert
      climate and has evolved protective mechanisms to limit oxidative stress. The
      mitochondrial kappa class glutathione transferase enzyme is a member of GST
      supergene family that represents an important enzyme group in cellular Phase II
      detoxification machinery and is involved in the protection against oxidative
      stress and xenobiotics. In the present study, C. dromedarius kappa class
      glutathione transferase (CdGSTK1-1) was cloned, expressed in E. coli BL21,
      purified and its structural, thermodynamic and unfolding pathway was
      investigated. The results showed that CdGSTK1-1 has unique trimeric structure,
      exhibits low thermostability and a complex equilibrium unfolding profile. It
      unfolds through three folding states with formation of thinly populated
      intermediate species. The melting points (Tm) of the first unfolding transition
      was 40.3+/-0.2 degrees C and Tm of the second unfolding transition was 49.1+/-0.1
      degrees C. The van't Hoff enthalpy of the first and second transition were
      298.7+/-13.2 and 616.5+/-2.4kJ/mol, respectively. Moreover, intrinsic
      fluorescence and near-UV CD studies indicates that substrate binding does not
      leads to major conformational changes in CdGSTK1-1. 

PMID- 27044345
TI  - Molecular structure, chemical properties and biological activities of Pinto bean
      pod polysaccharide.
AB  - Pinto bean pod polysaccharide (PBPP) was successfully extracted with yield of
      38.5g/100g and the PBPP gave total carbohydrate and uronic acid contents of
      286.2mg maltose equivalent/g and 374.3mgGal/g, respectively. The Mw of PBPP was
      270.6kDa with intrinsic viscosity of 0.262dm(3)/g, which composed of mannose
      (2.5%), galacturonic acid (15.0%), rhamnose (4.0%), glucose (9.0%), galactose
      (62.2%), xylose (2.9%) and arabinose (4.3%) with trace amount of ribose and
      fucose. The result suggested that PBPP has a spherical conformation with a highly
      branched structure. Fourier Transform Infrared analysis showed that PBPP has a
      similar structure as commercial pectin with an esterification degree of 59.9%,
      whereas scanning electron microscopy study showed that the crude polysaccharide
      formed a thin layer of film that was made of multiple micro strands of fibre.
      PBPP exhibited substantial free radical scavenging activity (7.7%), metal
      reducing capability (2.04mmol/dm(3)) and alpha-amylase inhibitory activity
      (97.6%) at a total amount of 1mg. PBPP also exhibited high water- and oil-holding
      capacities (3.6g/g and 2.8g/g, respectively). At a low concentration, PBPP
      exhibited emulsifying activity of 39.6% with stability of 38.6%. Apart from that,
      PBPP was able to show thickening capability at low concentration (0.005kg/dm(3)).

PMID- 27044346
TI  - Guar gum as a promising starting material for diverse applications: A review.
AB  - Guar gum is the powdered endosperm of the seeds of the Cyamopsis tetragonolobus
      which is a leguminous crop. The endosperm contains a complex polysaccharide
      called galactomannan, which is a polymer of d-galactose and d-mannose. This
      hydroxyl group rich polymer when added to water forms hydrogen bonding imparting
      significant viscosity and thickening to the solution. Due to its thickening,
      emulsifying, binding and gelling properties, quick solubility in cold water, wide
      pH stability, film forming ability and biodegradability, it finds applications in
      large number of industries. In last few decades a lot of research has been done
      on guar gum to fit it into particular application, as such or by its structural
      modifications. This review gives an overview of the nature, chemistry and
      properties of guar gum and discusses recent developments in its modifications and
      applications in major industries like hydraulic fracturing, explosives, food,
      agriculture, textile, paper, cosmetics, bioremediation, drug delivery, medical
      and pharmaceuticals. This article would help researchers engaged in biopolymer
      area and other end-users who want to begin research in natural polysaccharides. 

PMID- 27044347
TI  - New insights into xanthine oxidase behavior upon heating using spectroscopy and
      in silico approach.
AB  - Thermal dependent conformational changes of xanthine oxidase (XOD) were studied
      using sensitive and non-destructive methods like fluorescence spectroscopy and
      molecular modeling in the temperature range of 25-85 degrees C. Intrinsic
      fluorescence studies showed that the microenvironment of tryptophan and tyrosine
      residues becomes more exposed to solvent as the temperature increased up to 85
      degrees C, whereas in case of flavin cofactor is rather conserved. At higher
      temperatures, the flavin adenine dinucleotide is displaced from the core of the
      protein, but is not fully released as shown by the Stern Volmer quenching
      constant and accessible fraction of the cofactor. Anyway, no significant changes
      in the structure of XOD monomer were identified after running molecular dynamics
      simulations at temperatures 25 degrees C, 65 degrees C and 85 degrees C.
      Therefore, we can conclude that the most important changes in the protein
      structure at thermal treatment mainly consist on molecular aggregation and
      dissociation events. 

PMID- 27044348
TI  - Insights into the structure-function relationship of Brugia malayi thymidylate
      kinase (BmTMK).
AB  - Lymphatic filariasis is a debilitating disease caused by lymph dwelling nematodal
      parasites like Wuchereria bancrofti, Brugia malayi and Brugia timori. Thymidylate
      kinase of B. malayi is a key enzyme in the de novo and salvage pathways for
      thymidine 5'-triphosphate (dTTP) synthesis. Therefore, B. malayi thymidylate
      kinase (BmTMK) is an essential enzyme for DNA biosynthesis and an important drug
      target to rein in filariasis. In the present study, the structural and functional
      changes associated with recombinant BmTMK, in the presence of protein denaturant
      GdnHCl, urea and pH were studied. GdnHCl and urea induced unfolding of BmTMK is
      non-cooperative and influence the functional property of the enzyme much lower
      than their Cm values. The study delineate that BmTMK is more prone to ionic
      perturbation. The dimeric assembly of BmTMK is an absolute requirement for
      enzymatic acitivity and any subtle change in dimeric conformation due to
      denaturation leads to loss of enzymatic activity. The pH induced changes on
      structure and activity suggests that selective modification of active site
      microenvironment pertains to difference in activity profile. This study also
      envisages that chemical moieties which acts by modulating oligomeric assembly,
      could be used for better designing of inhibitors against BmTMK enzyme. 

PMID- 27044349
TI  - Recent progress on synthesis, property and application of modified chitosan: An
      overview.
AB  - Because of the unique chemical structure, chitosan and its derivatives have been
      paid close extensive attention as the potential bio-functional material. This
      review presents recent synthesis of modified chitosan via N-substitution, O
      substitution, free radical graft copolymerization and other modification methods
      and properties of the modified chitosan. The applications of the modified
      chitosan in metal ions adsorption, dye removal and pharmaceutical fields are
      illustrated as well. The rapid development in the modification of chitosan
      describes broad perspectives of the modified chitosan. 

PMID- 27044350
TI  - Cigarette Smoke Extract Causes Injury in Primary Retinal Ganglion Cells via
      Apoptosis and Autophagy.
AB  - AIMS: To investigate whether tobacco smoke directly injures retinal ganglion
      cells (RGCs) and to evaluate the mechanisms of cell death. METHODS: Primary rat
      RGCs were harvested from 3- or 4-day-old newborn rats and exposed to cigarette
      smoke extract (CSE). Cell viability was determined by adenosine 5'-triphosphate
      (ATP) assay. Apoptosis was evaluated by terminal deoxynucleotidyl transferase
      (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) and
      real-time reverse transcription polymerase chain reaction (RT-PCR) for Bcl-2
      family. Autophagy was also assessed by Western immunoblots for light chain (LC)
      3B. RESULTS: When the primary RGCs were exposed to CSE for 2 h, cell viability
      decreased in a dose-dependent manner, as measured by ATP assay. In the presence
      of 0.05% CSE, the RGC viability was 77.68% +/- 7.60% compared to the control
      cells; in the presence of 1.0% CSE, viability was 47.48% +/- 2.56% of the control
      cells. As determined by TUNEL, CSE increased the apoptotic RGCs in a dose
      dependent manner. In the presence of 0.05% CSE, the apoptosis was 26.55% +/-
      1.97% of the control cells; in the presence of 2.5% CSE, it was 41.07% +/- 3.75%
      of the control cells. When apoptosis was evaluated using real-time RT-PCR,
      exposure to 0.05% CSE resulted in significantly increased expression of Bad, Bax,
      Bcl-2, and Bcl-XL mRNA. When autophagy was assessed by Western immunoblots,
      exposure to 0.05% CSE significantly increased the expression of LC3B II.
      CONCLUSIONS: Our data suggest that CSE directly injures primary RGCs, and both
      cell death mechanisms of apoptosis and autophagy seem to be related to this CSE
      induced RGC damage.

PMID- 27044351
TI  - Convenient broad-host-range unstable vectors for studying stabilization cassettes
      in diverse bacteria.
AB  - BACKGROUND: Low-copy-number vectors of potential wide application in
      biotechnology need to encode stabilization modules ensuring their stable
      inheritance. The efficiency of stabilization may vary depending on the plasmid
      host so a thorough analysis of stabilization functions is required before use.
      RESULTS: To facilitate such analysis highly unstable, mobilizable, broad-host
      range (BHR) vectors based on RK2 replicon were constructed. The vectors are
      suitable for testing of various stabilization functions, including plasmid and
      chromosomal partitioning cassettes encoding ParB homologues capable of spreading
      on DNA. The xylE or lacZ reporter systems facilitate easy monitoring of plasmid
      segregation. CONCLUSION: The range of BHR vectors with different reporter
      cassettes and alternative mobilization systems expands their application in
      diverse bacterial species.

PMID- 27044352
TI  - Immune influences on the brain: new findings and implications for treatment.

PMID- 27044353
TI  - Nicotine-induced cortical activation among nonsmokers with moderation by trait
      cognitive control.
AB  - RATIONALE: Considerable research suggests that nicotine enhances cognitive
      control-related processes (e.g., attention, memory) among nicotine-deprived
      smokers, both in terms of behavior and neural indices (e.g., ERP, slow-wave EEG).
      Nicotine may also increase cognitive control among nonsmokers, and this may vary
      as a function of trait cognitive control. It is important to examine the effects
      of nicotine on cognitive control-related processes among nonsmokers as these
      effects may provide a path for the initiation of smoking. OBJECTIVES: The
      objectives of the study were to examine in nonsmokers (1) the effect of nicotine
      on resting cortical activity, an indirect measure of cognitive control, and (2)
      trait cognitive control as a moderator of nicotine-induced cortical activity
      changes. METHOD: Eighty participants were given placebo and 7-mg nicotine patches
      in separate sessions for this counter-balanced, double-blind, within-subject
      study. Resting cortical activity was measured with EEG for a 3-min period with
      eyes opened. RESULTS: Average alpha-1 band power density values in frontal and
      central regions were lower during the nicotine versus placebo condition, which
      provides evidence of nicotine-induced cortical activation. Furthermore, those
      with lower self-reported cognitive control exhibited greater nicotine-induced
      reductions in alpha-1 power density values. CONCLUSIONS: These individual
      differences in nicotine-induced cortical activation are consistent with a model
      of nicotine self-medication whereby individuals with lower cognitive control may
      find smoking more reinforcing via amelioration of related cognitive deficits.

PMID- 27044354
TI  - The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and
      DARPP-32 phosphorylation.
AB  - RATIONALE: Melanin-concentrating hormone (MCH) is involved in the regulation of
      food intake and has recently been associated with alcohol-related behaviors.
      Blockade of MCH-1 receptors (MCH1-Rs) attenuates operant alcohol self
      administration and decreases cue-induced reinstatement, but the mechanism through
      which the MCH1-R influences these behaviors remains unknown. MCH1-Rs are highly
      expressed in the nucleus accumbens shell (NAcSh) where they are co-expressed with
      dopamine (DA) receptors. MCH has been shown to potentiate responses to dopamine
      and to increase phosphorylation of DARPP-32, an intracellular marker of DA
      receptor activation, in the NAcSh. METHODS: In the present study, we investigated
      the role of the MCH1-R in alcohol reward using the conditioned place preference
      (CPP) paradigm. We then used immunohistochemistry (IHC) to assess activation of
      downstream signaling after administration of a rewarding dose of alcohol.
      RESULTS: We found that alcohol-induced CPP was markedly decreased in mice with a
      genetic deletion of the MCH1-R as well as after pharmacological treatment with an
      MCH1-R antagonist, GW803430. In contrast, an isocaloric dose of dextrose did not
      produce CPP. The increase in DARPP-32 phosphorylation seen in wildtype (WT) mice
      after acute alcohol administration in the NAcSh was markedly reduced in MCH1-R
      knock-out (KO) mice. CONCLUSION: Our results suggest that MCH1-Rs regulate the
      rewarding properties of alcohol through interactions with signaling cascades
      downstream of DA receptors in the NAcSh.

PMID- 27044355
TI  - Potential of sulfasalazine as a therapeutic sensitizer for CD44 splice variant 9
      positive urogenital cancer.
AB  - Cancer stem-like cells (CSCs) with high expression of CD44 splice variant (CD44v)
      have an enhanced capacity for intracellular reduced glutathione synthesis and
      defense against reactive oxygen species, resulting in resistance to various
      therapeutic stresses. Sulfasalazine (SSZ), a drug used in the treatment of
      rheumatoid arthritis (RA), inhibits glutamate-cystine transport, and suppressed
      CD44v-dependent tumor growth and increased sensitivity to cytotoxic drugs in an
      in vivo study. Here, we present two cases of CD44v9-positive urogenital cancer
      with concomitant treatment with SSZ for RA. Patient 1 was a 62-year-old man who
      had received SSZ for RA beginning 2 months before the diagnosis of urinary
      bladder cancer. Although he had multiple metastases to the bladder, abdominal,
      left cervical and left axillary lymph nodes, and brain, complete response with
      multidisciplinary therapy was maintained for more than 2 years. Patient 2 was a
      74-year-old man with castration-resistant prostate cancer who was diagnosed with
      RA during chemotherapy and a gradual increase in prostate-specific antigen (PSA)
      level. When SSZ was added, his PSA value (ng/mL) decreased from 12.93 to 5.58 in
      only 2 weeks and then quickly rebounded, whereas levels of neuron-specific
      enolase, a neuroendocrine differentiator and CSC marker, remained almost
      unchanged. We therefore speculate that SSZ treatment may represent a new adjuvant
      treatment option for patients with CD44v9-positive urogenital cancer. 

PMID- 27044356
TI  - FGFR3 promotes angiogenesis-dependent metastasis of hepatocellular carcinoma via
      facilitating MCP-1-mediated vascular formation.
AB  - The biological role of fibroblast growth factor receptor 3 (FGFR3) in tumor
      angiogenesis of hepatocellular carcinoma (HCC) has not been discussed before. Our
      previous work had indicated FGFR3 was overexpressed in HCC, and silencing FGFR3
      in Hu7 cells could regulate tumorigenesis via down-regulating the phosphorylation
      level of key members of classic signaling pathways including ERK and AKT. In the
      present work, we explored the role of FGFR3 in angiogenesis-dependent metastasis
      by using SMMC-7721 and QGY-7703 stable cell lines. Our results indicated FGFR3
      could regulate in vitro cell migration ability and in vivo lung metastasis
      ability of HCC, which was in accordance with increased angiogenesis ability in
      vitro and in vivo. Using the supernatant from SMMC-7721/FGFR3 cells, we conducted
      a human angiogenesis protein microarray including 43 angiogenesis factors and
      found that FGFR3 modulated angiogenesis and metastasis of HCC mainly by promoting
      the protein level of monocyte chemotactic protein 1 (MCP-1). Silencing FGFR3 by
      short hairpin RNA (shRNA) could reduce MCP-1 level in lysates and supernatant of
      QGY-7703 cells and SMMC-7721 cells. Silencing MCP-1 in QGY-7703 or SMMC-7721
      cells could induce similar phenotypes compared with silencing FGFR3. Our results
      suggested FGFR3 promoted metastasis potential of HCC, at least partially if not
      all, via facilitating MCP-1-mediated angiogenesis, in addition to previously
      found cell growth and metastasis. MCP-1, a key medium between HCC cells and
      HUVECs, might be a novel anti-vascular target in HCC. 

PMID- 27044357
TI  - Harm reduction policy in Taiwan: toward a comprehensive understanding of its
      making and effects.
AB  - BACKGROUND: In response to the spread of HIV caused by needle sharing among
      injection drug users (IDUs), the Taiwan Centers for Disease Control implemented a
      pilot harm reduction program in 2005 that expanded nationwide in 2006. The policy
      led to a significant reduction in the number of HIV-positive cases among IDUs in
      4 years. METHODS: This article aims to provide a critical evaluation of this harm
      reduction policy in Taiwan. The research leading to this article included a
      thorough literature review and in-depth interviews with 31 active policy
      participants, including people working in hospitals, the academia, non
      governmental organizations, community pharmacies, the legal system, and health
      authorities at both the central and local levels. The collected data were
      analyzed on the basis of situational analysis. RESULTS: The article examines the
      policy success by showing how this policy was assembled and by exposing the
      frictions and adjustments during its formation and implementation. Inter
      departmental conflicts within or without the government and the efforts to
      coordinate them are addressed, and the transnational dimensions of this harm
      reduction policy are also discussed. The article then reflects on the effects of
      the policy and asks where the line should be drawn between what is harm reduction
      and what is not. CONCLUSIONS: This case illustration reveals the complexity of
      understanding an assembled health policy that involves multiple participants. The
      article intends to render an analytic account to enable a comparison with similar
      policies in other countries.

PMID- 27044358
TI  - Diversity of flux distribution in central carbon metabolism of S. cerevisiae
      strains from diverse environments.
AB  - BACKGROUND: S. cerevisiae has attracted considerable interest in recent years as
      a model for ecology and evolutionary biology, revealing a substantial genetic and
      phenotypic diversity. However, there is a lack of knowledge on the diversity of
      metabolic networks within this species. RESULTS: To identify the metabolic and
      evolutionary constraints that shape metabolic fluxes in S. cerevisiae, we used a
      dedicated constraint-based model to predict the central carbon metabolism flux
      distribution of 43 strains from different ecological origins, grown in wine
      fermentation conditions. In analyzing these distributions, we observed a highly
      contrasted situation in flux variability, with quasi-constancy of the glycolysis
      and ethanol synthesis yield yet high flexibility of other fluxes, such as the
      pentose phosphate pathway and acetaldehyde production. Furthermore, these fluxes
      with large variability showed multimodal distributions that could be linked to
      strain origin, indicating a convergence between genetic origin and flux
      phenotype. CONCLUSIONS: Flux variability is pathway-dependent and, for some flux,
      a strain origin effect can be found. These data highlight the constraints shaping
      the yeast operative central carbon network and provide clues for the design of
      strategies for strain improvement.

PMID- 27044359
TI  - The Electroporation as a Tool for Studying the Role of Plasma Membrane in the
      Mechanism of Cytotoxicity of Bisphosphonates and Menadione.
AB  - In this study, the role of the cell plasma membrane as a barrier in the mechanism
      of the cytotoxicity of nitrogen-containing bisphosphonates and menadione was
      studied, and the possibility of increasing the efficiency of bisphosphonates and
      menadione (vitamin K3) as chemotherapeutic agents by permeabilizing the cell
      plasma membrane has been investigated in vitro. The plasma membrane barrier was
      reduced by electropermeabilization with the pulse of strong electric field. Two
      membrane-impermeant bisphosphonates with different hydrophilicities were chosen
      as study objects: ibandronate and pamidronate. For the comparison, an amphiphilic
      vitamin K3, which is able to cross the cell membrane, was studied as well. The
      impact of nitrogen-containing bisphosphonates and vitamin K3 on MH-22A cells
      viability was evaluated for the case of long (9 days) and short (20 min)
      exposure. When cells were cultured in the medium with vitamin K3 for 9-10 days,
      it exhibited toxicity of 50 % over the control at 6.2 uM for mouse hepatoma MH
      22A cells. Ibandronate and pamidronate were capable of reducing drastically the
      cell viability only in the case of long 9-days incubation and at high
      concentrations (~20 uM for pamidronate and over 100 uM for ibandronate). Single,
      square-wave electric pulse with the duration of 100 us and the field strength of
      2 kV/cm was used to electroporate mouse hepatoma MH-22A cells in vitro. The
      results obtained here showed that the combination of the exposure of cells to
      membrane-impermeable bisphosphonates pamidronate and ibandronate with
      electropermeabilization of the cell plasma membrane did not increase their
      cytotoxicity. In the case of membrane-permeable vitamin K3, cell
      electropermeabilization did increase vitamin K3 killing efficiency. However, this
      increase was not substantial, within the range of 20-30 % depending on the
      duration of the exposure. Electropermeabilization improved cytotoxic effect of
      vitamin K3 but not of pamidronate and ibandronate.

PMID- 27044360
TI  - A protocol for a pragmatic randomized controlled trial using the Health Teams
      Advancing Patient Experience: Strengthening Quality (Health TAPESTRY) platform
      approach to promote person-focused primary healthcare for older adults.
AB  - BACKGROUND: Healthcare systems are not well designed to help people maintain or
      improve their health. They are generally not person-focused or well-coordinated.
      The objective of this study is to evaluate the effectiveness of the Health Teams
      Advancing Patient Experience: Strengthening Quality (Health TAPESTRY) approach in
      older adults. The overarching hypothesis is that using the Health TAPESTRY
      approach to achieve better integration of the health and social care systems into
      a person's life that centers on meeting a person's health goals and needs will
      result in optimal aging. METHODS/DESIGN: This is a 12-month delayed intervention
      pragmatic randomized controlled trial. The study will be performed in Hamilton,
      Ontario, Canada in the two-site McMaster Family Health Team. Participants will
      include 316 patients who are 70 years of age or older. Participants will be
      randomized to the Health TAPESTRY approach or control group. The Health TAPESTRY
      approach includes intentional, proactive conversations about a person's life and
      health goals and health risks and then initiation of congruent tailored
      interventions that support achievement of those goals and addressing of risks
      through (1) trained volunteers visiting clients in their homes to serve as a link
      between the primary care team and the client; (2) the use of novel technology
      including a personal health record from the home to link directly with the
      primary healthcare team; and (3) improved processes for connections, system
      navigation, and care delivery among interprofessional primary care teams,
      community service providers, and informal caregivers. The primary outcome will be
      the goal attainment scaling score. Secondary outcomes include self-efficacy for
      managing chronic disease, quality of life, the participant perspective on their
      own aging, social support, access to health services, comprehensiveness of care,
      patient empowerment, patient-centeredness, caregiver strain, satisfaction with
      care, healthcare resource utilization, and cost-effectiveness. Implementation
      processes will also be evaluated. The main comparative analysis will take place
      at 6 months. DISCUSSION: Evidence of the individual elements of the Health
      TAPESTRY platform has been shown in isolation in the previous research. However,
      this study will better understand how to best integrate them to maximize the
      system's transformation of person-focused, primary care for older adults. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02283723.

PMID- 27044361
TI  - Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on
      Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit.
AB  - Endothelial dysfunctions that include decreased nitric oxide (NO) bioactivity and
      increased endothelin-1 (ET-1) bioactivity have been considered to be involved in
      the pathogenesis of cerebral vasospasm (CVS) after aneurysmal subarachnoid
      hemorrhage (SAH). Recent cardiovascular studies have revealed that cyclooxygenase
      2 (COX-2) is involved in a disturbance in cross-talk between NO and ET-1. COX-2
      expression was detected in the endothelial cells of a spastic artery after
      experimental SAH; however, the pathophysiological significance of COX-2 in
      relation to CVS remains unclear. The aim of this study was to investigate the
      role of COX-2 in relation to NO and ET-1 in the pathogenesis of CVS by using the
      COX-2 selective inhibitor, celecoxib. In the SAH group, SAH was simulated using
      the double-hemorrhage rabbit model. In the celecoxib group, SAH was simulated and
      celecoxib was administered. The basilar artery was extracted on day 5 and
      examined. The cross-section area of the basilar artery in the celecoxib group was
      significantly larger than in the SAH group. An increased expression of COX-2, ET
      1, and ETA receptor (ETAR), and a decreased expression of endothelial NO synthase
      (eNOS) were seen in the SAH group. In the celecoxib group compared to the SAH
      group, expression of COX-2, ET-1, and ETAR were statistically significantly
      decreased, and eNOS expression was significantly increased. COX-2 might be
      involved in the pathogenesis of CVS due to up-regulation of ET-1 and ETAR and
      down-regulation of eNOS, and celecoxib may potentially serve as an agent in the
      prevention of CVS after SAH.

PMID- 27044362
TI  - Assessment and interpretation of internal doses: uncertainty and variability.
AB  - Internal doses are calculated on the basis of knowledge of intakes and/or
      measurements of activity in bioassay samples, typically using reference
      biokinetic and dosimetric models recommended by the International Commission on
      Radiological Protection (ICRP). These models describe the behaviour of the
      radionuclides after ingestion, inhalation, and absorption to the blood, and the
      absorption of the energy resulting from their nuclear transformations. They are
      intended to be used mainly for the purpose of radiological protection: that is,
      optimisation and demonstration of compliance with dose limits. These models and
      parameter values are fixed by convention and are not subject to uncertainty. Over
      the past few years, ICRP has devoted a considerable amount of effort to the
      revision and improvement of models to make them more physiologically realistic.
      ICRP models are now sufficiently sophisticated for calculating organ and tissue
      absorbed doses for scientific purposes, and in many other areas, including
      toxicology, pharmacology and medicine. In these specific cases, uncertainties in
      parameters and variability between individuals need to be taken into account. 

PMID- 27044363
TI  - Cosmic radiation in aviation: radiological protection of Air France aircraft
      crew.
AB  - Cosmic radiation in aviation has been a concern since the 1960s, and measurements
      have been taken for several decades by Air France. Results show that aircraft
      crew generally receive 3-4 mSv y(-1) for 750 boarding hours. Compliance with the
      trigger level of 6 mSv y(-1) is achieved by route selection. Work schedules can
      be developed for pregnant pilots to enable the dose to the fetus to be kept below
      1 mSv. Crew members are informed of their exposition and the potential health
      impact. The upcoming International Commission on Radiological Protection (ICRP)
      report on cosmic radiation in aviation will provide an updated guidance. A graded
      approach proportionate with the time of exposure is recommended to implement the
      optimisation principle. The objective is to keep exposures of the most exposed
      aircraft members to reasonable levels. ICRP also recommends that information
      about cosmic radiation be disseminated, and that awareness about cosmic radiation
      be raised in order to favour informed decision-making by all concerned
      stakeholders. 

PMID- 27044364
TI  - ICRP 2015 - the Third International Symposium on the System of Radiological
      Protection.

PMID- 27044365
TI  - Ethics of radiological risk governance: justice of justification as a central
      concern.
AB  - Due to the specific character of the radiological risk, judgements on whether the
      use of nuclear technology would be justified in society have to consider
      knowledge-related uncertainties and value pluralism. The justice of justification
      not only informs the right of the potentially affected to participate in decision
      making, but also implies the responsibility of concerned actors to give account
      of the way they rationalise their own position, interests, hopes, hypotheses,
      beliefs, and concerns in knowledge generation and decision making. This paper
      characterises the evaluation of whether the use of nuclear technology would be
      justified in society as a 'complex social problem', and reflects on what it would
      imply to deal with its complexity fairly. Based on this assessment, the paper
      proposes 'reflexivity' and 'intellectual solidarity' as ethical attitudes or
      virtues for all concerned actors, to be understood from a specific 'ethics of
      care' perspective 'bound in complexity'. Consequently, it argues that there is a
      need for an 'interactive' understanding of ethics in order to give ethical
      attitudes or virtues a practical meaning in a sociopolitical context, and draws
      conclusions for the case of radiological risk governance. 

PMID- 27044366
TI  - Detailed analysis of sputum and systemic inflammation in asthma phenotypes: are
      paucigranulocytic asthmatics really non-inflammatory?
AB  - BACKGROUND: The technique of induced sputum has allowed to subdivide asthma
      patients into inflammatory phenotypes according to their level of granulocyte
      airway infiltration. There are very few studies which looked at detailed sputum
      and blood cell counts in a large cohort of asthmatics divided into inflammatory
      phenotypes. The purpose of this study was to analyze sputum cell counts, blood
      leukocytes and systemic inflammatory markers in these phenotypes, and investigate
      how those groups compared with healthy subjects. METHODS: We conducted a
      retrospective cross-sectional study on 833 asthmatics recruited from the
      University Asthma Clinic of Liege and compared them with 194 healthy subjects.
      Asthmatics were classified into inflammatory phenotypes. RESULTS: The total non
      squamous cell count per gram of sputum was greater in mixed granulocytic and
      neutrophilic phenotypes as compared to eosinophilic, paucigranulocytic asthma and
      healthy subjects (p < 0.005). Sputum eosinophils (in absolute values and
      percentages) were increased in all asthma phenotypes including paucigranulocytic
      asthma, compared to healthy subjects (p < 0.005). Eosinophilic asthma showed
      higher absolute sputum neutrophil and lymphocyte counts than healthy subjects (p
      < 0.005), while neutrophilic asthmatics had a particularly low number of sputum
      macrophages and epithelial cells. All asthma phenotypes showed an increased blood
      leukocyte count compared to healthy subjects (p < 0.005), with paucigranulocytic
      asthmatics having also increased absolute blood eosinophils compared to healthy
      subjects (p < 0.005). Neutrophilic asthma had raised CRP and fibrinogen while
      eosinophilic asthma only showed raised fibrinogen compared to healthy subjects (p
      < 0.005). CONCLUSIONS: This study demonstrates that a significant eosinophilic
      inflammation is present across all categories of asthma, and that
      paucigranulocytic asthma may be seen as a low grade inflammatory disease.

PMID- 27044367
TI  - Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: For most cancers, only a minority of patients have symptoms meeting
      the National Institute for Health and Clinical Excellence guidance for urgent
      referral. For gastro-oesophageal cancers, the 'alarm' symptoms of dysphagia and
      weight loss are reported by only 32 and 8 % of patients, respectively, and their
      presence correlates with advanced-stage disease. Electronic clinical decision
      support tools that integrate with clinical computer systems have been developed
      for general practice, although uncertainty remains concerning their
      effectiveness. The objectives of this trial are to optimise the intervention and
      establish the acceptability of both the intervention and randomisation, confirm
      the suitability and selection of outcome measures, finalise the design for the
      phase III definitive trial, and obtain preliminary estimates of the intervention
      effect. METHODS/DESIGN: This is a two-arm, multi-centre, cluster-randomised,
      controlled phase II trial design, which will extend over a 16-month period,
      across 60 general practices within the North East and North Cumbria and the
      Eastern Local Clinical Research Network areas. Practices will be randomised to
      receive either the intervention (the electronic clinical decision-support tool)
      or to act as a control (usual care). From these practices, we will recruit 3000
      adults who meet the trial eligibility criteria and present to their GP with
      symptoms suggestive of gastro-oesophageal cancer. The main measures are the
      process data, which include the practitioner outcomes, service outcomes,
      diagnostic intervals, health economic outcomes, and patient outcomes. One-on-one
      interviews in a sub-sample of 30 patient-GP dyads will be undertaken to
      understand the impact of the use or non-use of the electronic clinical decision
      support tool in the consultation. A further 10-15 GPs will be interviewed to
      identify and gain an understanding of the facilitators and constraints
      influencing implementation of the electronic clinical decision-support tool in
      practice. DISCUSSION: We aim to generate new knowledge on the process measures
      regarding the use of electronic clinical decision-support tools in primary care
      in general and to inform a subsequent definitive phase III trial. Preliminary
      data on the impact of the support tool on resource utilisation and health care
      costs will also be collected. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN12595588
      .

PMID- 27044368
TI  - CTGF promotes articular damage by increased proliferation of fibroblast-like
      synoviocytes in rheumatoid arthritis.
AB  - OBJECTIVES: Fibroblast-like synoviocytes (FLS) are a major component of the
      hyperplastic synovial pannus, which aggressively invades cartilage and bone
      during the course of rheumatoid arthritis (RA). Connective tissue growth factor
      (CTGF or CCN2) is a product of a growth factor-inducible immediate early gene and
      is involved in cell adhesion, proliferation, and differentiation. However, the
      role that CTGF plays in FLS proliferation has remained undetermined. The aim of
      this study was to identify the role of CTGF in regulating the proliferation of
      FLS derived from patients with RA. METHOD: CTGF levels in serum and synovial
      fluid (SF) were determined by enzyme-linked immunosorbent assay (ELISA).
      Expression of CTGF in FLS was determined using reverse transcription polymerase
      chain reaction (RT-PCR). FLS proliferation stimulated by CTGF was measured by
      thymidine incorporation. The influence of CTGF small interfering RNA (siRNA) on
      FLS apoptosis was detected by flow cytometry. RESULTS: CTGF was overexpressed in
      serum and SF samples from RA patients compared with samples from normal controls.
      Elevated levels of CTGF in RA SF promoted the proliferation of FLS. Furthermore,
      in samples from RA patients, CTGF was found to protect FLS from apoptosis and to
      sustain the expression of survivin in FLS. The expression of CTGF in FLS can be
      up-regulated by tumour necrosis factor (TNF)-alpha. CONCLUSIONS: Our findings
      indicate that CTGF plays a crucial role in the proliferation of FLS in RA and
      probably contributes to synovial lining cell hyperplasia and eventually to joint
      destruction in patients with RA.

PMID- 27044369
TI  - Environmental Risk Assessment of Pharmaceutical Mixtures: Demands, Gaps, and
      Possible Bridges.
AB  - The ecotoxicological risk of pharmaceutical mixtures typically exceeds the risk
      of each individual compound, which calls specific attention to the fact that
      monitoring surveys routinely find complex pharmaceutical mixtures in various
      environmental compartments. However, although the body of evidence on the
      ecotoxicology of pharmaceutical mixtures is quite consistent, the current
      guidelines for the environmental risk assessment of pharmaceuticals often do not
      explicitly address mixture effects. Data availability and acceptable methods
      often limit such assessments. A tiered approach that begins with summing up
      individual risk quotients, i.e., the ratio between the predicted or measured
      environmental concentration and the predicted no effect concentration (PNEC) is
      therefore suggested in this paper, in order to improve the realism of the
      environmental risk assessment of pharmaceuticals. Additionally, the use of a
      mixture-specific assessment factor, as well as the classical mixture toxicity
      concepts of concentration addition and independent action is explored. Finally,
      specific attention is given to the exposure-based waiving of environmental risk
      assessments, as currently implemented in screening or pre-screening phases (tier
      0 in Europe, categorical exclusion in the USA), since even low, individually non
      toxic concentrations might combine to produce substantial mixture effects.

PMID- 27044370
TI  - Monitoring Quality of Biotherapeutic Products Using Multivariate Data Analysis.
AB  - Monitoring the quality of pharmaceutical products is a global challenge,
      heightened by the implications of letting subquality drugs come to the market on
      public safety. Regulatory agencies do their due diligence at the time of approval
      as per their prescribed regulations. However, product quality needs to be
      monitored post-approval as well to ensure patient safety throughout the product
      life cycle. This is particularly complicated for biotechnology-based therapeutics
      where seemingly minor changes in process and/or raw material attributes have been
      shown to have a significant effect on clinical safety and efficacy of the
      product. This article provides a perspective on the topic of monitoring the
      quality of biotech therapeutics. In the backdrop of challenges faced by the
      regulatory agencies, the potential use of multivariate data analysis as a tool
      for effective monitoring has been proposed. Case studies using data from several
      insulin biosimilars have been used to illustrate the key concepts.

PMID- 27044371
TI  - High mobility and high stability glassy metal-oxynitride materials and devices.
AB  - In thin film technology, future semiconductor and display products with high
      performance, high density, large area, and ultra high definition with three
      dimensional functionalities require high performance thin film transistors (TFTs)
      with high stability. Zinc oxynitride, a composite of zinc oxide and zinc nitride,
      has been conceded as a strong substitute to conventional semiconductor film such
      as silicon and indium gallium zinc oxide due to high mobility value. However,
      zinc oxynitride has been suffered from poor reproducibility due to relatively low
      binding energy of nitrogen with zinc, resulting in the instability of composition
      and its device performance. Here we performed post argon plasma process on zinc
      oxynitride film, forming nano-crystalline structure in stable amorphous matrix
      which hampers the reaction of oxygen with zinc. Therefore, material properties
      and device performance of zinc oxynitride are greatly enhanced, exhibiting robust
      compositional stability even exposure to air, uniform phase, high electron
      mobility, negligible fast transient charging and low noise characteristics.
      Furthermore, We expect high mobility and high stability zinc oxynitride
      customized by plasma process to be applicable to a broad range of semiconductor
      and display devices. 

PMID- 27044372
TI  - Effects of Atorvastatin on Conservative and Surgical Treatments of Chronic
      Subdural Hematoma in Patients.
AB  - OBJECTIVE: To investigate effects of atorvastatin on conservative and surgical
      treatment of patients with chronic subdural hematoma. METHODS: A retrospective
      analysis was performed of 109 patients (including 3 outpatients) with chronic
      subdural hematoma at Northern Jiangsu People's Hospital from April 2014 to
      October 2015. Patients' gender, age, Glasgow Coma Scale score, symptoms, history
      of antiplatelet or anticoagulant use, hematoma location, volume of hematoma,
      operation methods, and application of atorvastatin and its duration were
      recorded. Prognostic indicators including changes in hematoma volume and
      neurologic status were extracted. Statistical methods were conducted to evaluate
      drug efficacy. RESULTS: Seven conservative patients received atorvastatin for 1-6
      months (range, 3.57 +/- 1.72 months). The volume of hematomas was +/- 4.49 mL to
      11.40 +/- 4.46 mL (P > 0.05) after 1 month's atorvastatin treatment. Hematomas
      disappeared after 6 months in all 7 patients. In surgical patients, gender (P =
      0.797), age (P = 0.063), Glasgow Coma Scale score (P = 0.216), history of
      antiplatelet or anticoagulant (P = 0.350), volume of hematoma after admission (P
      = 0.896), location (P = 0.282), and operation methods (P = 0.832) were
      nonsignificantly associated with follow-up groups, but atorvastatin was
      significantly associated with follow-up results (P = 0.045). CONCLUSIONS:
      Atorvastatin has preliminarily been proved to be safe and effective for chronic
      subdural hematomas in both conservative and surgical patients and can provide a
      drug treatment strategy for neurosurgeons.

PMID- 27044373
TI  - Posterior Cerebral Artery Aneurysms: Treatment and Outcome Analysis in 121
      Patients.
AB  - OBJECTIVE: Aneurysms of the posterior cerebral artery (PCA) are uncommon. Because
      of their low incidence, only 5 series with more than 30 patient cases have been
      reported. The treatment of PCA aneurysms is challenging because of the high
      frequency of fusiform aneurysms and closeness to important neuroanatomic
      structures. METHODS: A total of 121 patients with 135 PCA aneurysms were
      reviewed. The clinical and radiologic data, treatment strategies, and 1-year
      outcomes were analyzed. Patients with giant aneurysms, associated aneurysms, and
      aneurysms on arteriovenous malformation-feeding PCAs were considered as complex
      cases. Outcomes were categorized into 3 groups: good (modified Rankin Scale
      [mRS], score 0-1), moderate (mRS score, 2-4), and poor (mRS score, 5-6). RESULTS:
      There were 52 ruptured (39%) and 83 unruptured (61%) PCA aneurysms in 121
      patients, with the following distribution: P1 (n = 53), P1/2 (n = 39), P2 (n =
      28), and P3 (n = 15). The incidence of fusiform PCA aneurysms was high (24%).
      Microsurgical treatment was applied to 63 aneurysms and endovascular treatment to
      19 aneurysms; 55 aneurysms were treated conservatively. The following treatment
      results were achieved: for patients with unruptured PCA aneurysms, n = 19; 12
      good outcomes, 63%; 6 moderate, 31%; 1 poor, 1%; for patients with ruptured PCA
      aneurysms, n = 27; 10 good, 37%; 9 moderate, 33%; 8 poor, 30%; and for patients
      with complex neurovascular diseases and PCA aneurysms, n = 96; 42 good, 43%; 40
      moderate, 42%; 14 poor, 15%. CONCLUSIONS: Aneurysms of the PCA are infrequent and
      often associated with other vascular diseases. Microsurgery and endovascular
      treatment are effective for the occlusion of PCA aneurysms. The preservation or
      reconstruction of the parent vessel is crucial for favorable treatment outcomes.

PMID- 27044374
TI  - 23rd Annual Scientific Meeting of the European Society of Musculoskeletal
      Radiology (ESSR), Zurich, Switzerland, June 9-11, 2016.

PMID- 27044375
TI  - Multifocal low-grade central osteosarcoma: a rare case.
AB  - Low-grade central osteosarcoma (LGCOS) is a rare variant of osteosarcoma. We
      present a rare case of multifocal LGCOS located in two distinct skeletal sites,
      initially noted as incidental findings on imaging for distant traumatic
      pathology. Both sites seemed small and innocuous on initial imaging, and were
      quiescent clinically, illustrating the value of close interval multimodal
      surveillance scanning. 

PMID- 27044376
TI  - Regular physical activity and cardiovascular biomarkers in prevention of
      atherosclerosis in men: a 25-year prospective cohort study.
AB  - BACKGROUND: The purpose of the study was to examine the association between
      leisure-time physical activity (LTPA), cardiovascular biomarkers and
      atherosclerosis among asymptomatic men with stable LTPA level throughout the 25
      year prospective observation. METHODS: Out of 101 asymptomatic men prospectively
      observed for their lifestyle and cardiovascular risk factors, the cohort of 62
      individuals (mean age 59.9 years) maintained a stable LTPA level during the 25
      year observation. Regular check-ups with the assessment of traditional risk
      factors, detailed measurements of LTPA level and aerobic capacity were performed
      since baseline. At the latest follow-up (2011/12) a set of cardiovascular
      biomarkers was measured using enzyme-linked immunosorbent assay. Subclinical
      atherosclerosis was assessed by means of coronary artery calcification score and
      intima-media thickness (IMT). Endothelial function was evaluated by means of the
      reactive hyperemia index. The studied biomarkers and indices were analyzed in the
      three cohorts representing stable low-tomoderate (<2050 kcal/week), high (2050
      3840 kcal/week) and very high LTPA (>3840 kcal/week). RESULTS: At baseline the
      three cohorts were comparable in terms of age and clinical characteristics. At
      follow-up, the cohort with stable high LTPA (2050-3840 kcal/week) had
      significantly lower concentrations of hs-CRP (2.20 +/- 1.0 mg/L), oxidized-LDL
      (68.35 +/- 67.7 ng/mL), leptin (4.71 +/- 3.07 ng/mL) and irisin (0.47 +/- 0.13
      MUmol/L), and the most favorable indices of atherosclerosis and endothelial
      function as compared with other groups (p < 0.05). Regular marathon runners had
      increased concentrations of hsCRP (3.12 +/- 1.4 mg/L), oxidized-LDL (249.8 +/-
      129 ng/ml), Interleukine-6 (3.74 +/- 2.4 pg/ml). A positive correlation was
      observed between hsCRP and IMT (r = 0.301; p < 0.01), and irisin and IMT (r =
      0.223; p < 0.05). CONCLUSIONS: The data suggest that stable high LTPA (2050-3840
      kcal/week) is associated with the most favorable profile of key cardiovascular
      biomarkers and indices of atherosclerosis. Lifetime very high LTPA is associated
      with increased lowgrade inflammation and may, therefore, exert an atherogenic
      effect.

PMID- 27044377
TI  - Pigs in Toxicology: Breed Differences in Metabolism and Background Findings.
AB  - Both a rodent and a nonrodent species are required for evaluation in nonclinical
      safety studies conducted to support human clinical trials. Historically, dogs and
      nonhuman primates have been the nonrodent species of choice. Swine, especially
      the miniature swine or minipigs, are increasingly being used in preclinical
      safety as an alternate nonrodent species. The pig is an appropriate option for
      these toxicology studies based on metabolic pathways utilized in xenobiotic
      biotransformation. Both similarities and differences exist in phase I and phase
      II biotransformation pathways between humans and pigs. There are numerous breeds
      of pigs, yet only a few of these breeds are characterized with regard to both
      xenobiotic-metabolizing enzymes and background pathology findings. Some specific
      differences in these enzymes based on breed and sex are known. Although swine
      have been used extensively in biomedical research, there is also a paucity of
      information in the current literature detailing the incidence of background
      lesions and differences between commonly used breeds. Here, the xenobiotic
      metabolizing enzymes are compared between humans and pigs, and minipig background
      pathology changes are reviewed with emphasis on breed differences.

PMID- 27044378
TI  - Non-ossifying fibroma: natural history with an emphasis on a stage-related
      growth, fracture risk and the need for follow-up.
AB  - BACKGROUND: The aim of this study was to assess and present the radiological
      morphology of the non-ossifying fibroma (NOF), to describe the life span
      according to the Ritschl-stages in an effort to determine critical stages with
      regard to pathological fractures and discuss the need for a follow-up. METHODS:
      Reports of a consecutive series of 87 patients with 103 NOFs and a mean follow-up
      of 27 months were analysed according to the Ritschl-stages with regard to age at
      time of diagnosis, localisation, duration of stage and symptoms. RESULTS: Mean
      patient age in our series was 20 years and lesions most frequently affected the
      long bones of the lower extremity. Nineteen lesions were categorized in stage A,
      53 in stage B, 17 in stage C and 14 in stage D. Most lesions were detected
      incidentally. In six of ten clinically symptomatic patients with an average age
      of ten years a pathological fracture occurred, and four of them were located in
      the tibia. All of these were in stage B with a mean length of 44 mm, an average
      expansion in relation to the bone-diameter of 75 % in transversal and 87 % in
      sagittal plane. Duration of the stages was variable. In the critical stage B the
      mean was 21 months. CONCLUSION: The non-ossifying fibroma follows a
      characteristic radiomorphological course with variable duration of each stage.
      Stage B lesions were found to be at an increased risk of fracture, and the age
      range over which fractures occur was wide. No fractures were detected in the
      other three stages. Follow-up, including clinical survey and imaging, at six to
      twelve month intervals may therefore be considered in the case of larger stage B
      lesions until stage C is reached.

PMID- 27044379
TI  - Efficacy of four commercially available heartworm preventive products against the
      JYD-34 laboratory strain of Dirofilaria immitis.
AB  - BACKGROUND: Heartworm disease in dogs can be severe and life threatening.
      Resistance to available heartworm preventives was considered among potential
      causes of increased reports of failed heartworm prevention in dogs. The objective
      of the present study was to compare the efficacy of four commercially available
      heartworm disease preventives against the JYD-34 strain of D. immitis. METHODS:
      Forty laboratory-reared dogs approximately 6 months old were used. Each dog was
      infected with fifty, third-stage heartworm larvae on study day (SD) -30. On SD-1,
      the dogs were randomized to five groups of eight dogs each. On SD-0, dogs in
      groups 1-4 were treated as follows: Group 1: ivermectin/pyrantel pamoate chewable
      tablets; Group 2: milbemycin oxime/spinosad tablets; Group 3: selamectin topical
      solution; and Group 4: imidacloprid/moxidectin topical solution. Dogs in Group 5
      were not treated and served as controls. The dogs were treated according to their
      current body weights and labelled dose banding for each product. Groups 1, 2, and
      3 were retreated with their respective products and current body weights on SD 31
      and 60. On SDs 124-126 the dogs were euthanized and necropsied for recovery of
      adult heartworms. RESULTS: Adult heartworms were recovered at necropsy from each
      of the dogs in the control group (13-32 worms/dog, geometric mean (GM) = 18.4
      worms/dog). Adult heartworms and/or worm fragments were also recovered from each
      of the dogs treated with ivermectin/pyrantel pamoate, milbemycin oxime/spinosad
      or selamectin. Geometric means of worms recovered from dogs in each of these
      groups were 13.1, 8.8, and 13.1, resulting in efficacies compared to controls of
      29.0, 52.2, and 28.8 %, respectively. All dogs in Group 4
      (imidacloprid/moxidectin) were free of adult heartworms (100 % efficacy).
      CONCLUSIONS: The combination of imidacloprid/moxidectin was 100 % effective in
      this study in preventing development of JYD-34 laboratory strain of D. immitis in
      dogs following a single treatment, while three monthlytreatments of the three
      other commercial products provided less than 100 % efficacy. The high efficacy
      achieved with imidacloprid/moxidectin was likely due to the unique
      pharmacokinetic properties of the topical formulation delivering greater and
      sustained drug concentrations necessary to prevent development of D. immitis
      larvae.

PMID- 27044380
TI  - Personalized Medicine in Pediatrics: The Clinical Potential of Orodispersible
      Films.
AB  - Children frequently receive medicines that are designed for adults. The dose of
      commercially available products is adapted, mostly based on the child's
      bodyweight, thereby neglecting differences in pharmacokinetic and
      pharmacodynamics parameters. If commercial products are unsuitable for
      administration to children or are unavailable, extemporaneous pharmacy
      preparations are a good alternative. For this particular population,
      orodispersible films (ODFs) can be a highly attractive dosage form for the oral
      administration of drugs. ODFs are relatively easy to prepare in a hospital
      setting, create dose flexibility, and may suit an individual approach, especially
      for patients having difficulties in swallowing tablets or being fluid restricted.
      In this article, various aspects related to pharmacy preparations, clinical
      application, and preparation of ODFs for pediatric patients are highlighted and
      discussed.

PMID- 27044381
TI  - High miR-96 levels in colorectal adenocarcinoma predict poor prognosis,
      particularly in patients without distant metastasis at the time of initial
      diagnosis.
AB  - MicroRNA-96 (miR-96) is an oncomiR that facilitates the development of malignant
      tumors by promoting growth, proliferation, and survival of cancer cells. Previous
      studies using high-throughput techniques have shown that miR-96 is upregulated in
      colorectal cancer compared to adjacent normal colorectal tissue. The aim of this
      study was the investigation of the potential clinical value of miR-96 as a
      molecular prognostic biomarker in colorectal adenocarcinoma. For this purpose,
      total RNA was extracted from 108 primary colorectal adenocarcinoma samples and 54
      paired non-cancerous colorectal tissue specimens. After polyadenylation and
      reverse transcription, miR-96 molecules were determined using an in-house
      developed real-time quantitative PCR based on SYBR Green chemistry. Calculations
      were carried out with the comparative CT method, using SNORD48 as endogenous
      reference gene. Finally, extensive biostatistical analysis was performed and
      showed that miR-96 is significantly upregulated in colorectal adenocarcinoma
      specimens compared to their non-cancerous counterparts (p < 0.001) as well as in
      tumors having invaded regional lymph nodes (p = 0.009) and those of advanced TNM
      stage (p = 0.008). miR-96 expression is an unfavorable prognostic marker in
      colorectal adenocarcinoma, predicting poor disease-free and overall survival (p =
      0.041 and 0.028, respectively), independently of classical clinicopathological
      parameters. Most importantly, miR-96 expression stratifies patients without
      distant metastasis (M0) at the time of diagnosis into two groups with
      substantially different prognosis (p = 0.040). In conclusion, high tissue levels
      of miR-96 are associated with advanced stages of colorectal adenocarcinoma and
      predict an increased risk for disease recurrence and poor overall survival,
      especially in patients without distant metastasis at the time of diagnosis.

PMID- 27044382
TI  - Erratum to: FDG-PET/ceCT is useful to predict recurrence of Pseudomyxoma
      peritonei.

PMID- 27044383
TI  - Erratum to: Vesicular monoamine transporter protein expression correlates with
      clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report
      from the Children's Oncology Group.

PMID- 27044384
TI  - The impact of chronic disease on orphans' quality of life living in extended
      social care services: a cross sectional analysis.
AB  - BACKGROUND: Owing to a scarcity of data or other causes, patient research on the
      orphan population is lacking in most societies. Consequently, the primary goal of
      this study was to explore quality of life (QOL) and quality of care (QOC) among
      orphan patients (OPs) receiving tertiary healthcare services in Saudi Arabia
      (SA). METHOD: This study used a cross-sectional, quantitative survey design.
      Participants included 216 OPs either currently undergoing or who had undergone
      treatment for common chronic diseases (CDs) (e.g. cardiovascular disease, cancer,
      stroke and arthritis) during the past 12 months. The survey utilised the brief
      form from the World Health Organization Quality of Life (WHOQOL-BREF) tool and
      evaluated healthcare access and effectiveness domains to scrutinise the socio
      medical patterns of OPs based on their current medical episodes. RESULTS: The
      descriptive analysis indicated that OPs' overall QOL reached a moderate level (M
      = 3.90). Similarly, participants reported relatively high levels of healthcare
      access and treatment effectiveness (M = 4.14 and M = 4.29, respectively). Stroke
      patients reported the highest QOL score (M = 3.95), and groups of patients with
      other CDs reported greater access to healthcare and more effective treatment
      maintenance compared to the other groups (M = 4.19 and M = 4.43, respectively).
      Regression analysis was conducted to predict overall QOL based on perceived QOC,
      and access explained only 6.5 % of the variance. An analysis of variance showed
      significant differences only between OPs with cardiovascular disease and cancer
      (P = .001), with the former reporting better access to tertiary healthcare
      services than the latter. CONCLUSIONS: Although some CD patients reported
      relatively acceptable levels of access to healthcare and receipt of effective
      treatment, the improvement of OPs' QOL and QOC poses a serious challenge for
      health policymakers.

PMID- 27044385
TI  - Where is the exact origin of narrow premature ventricular contractions
      manifesting qR in inferior wall leads?
AB  - BACKGROUND: In recent years, radiofrequency catheter ablation(RFCA) has been
      established as an effective therapy for idiopathic premature ventricular
      contractions (PVCs), however, its effect on the narrow PVCs (QRS duration < 130
      msec) with qR pattern in inferior leads, may not been fully concluded. METHODS:
      Characteristics of 12-lead electrocardiogram (ECG) and electrophysiologic
      recordings were analyzed in 40 patients with symptomatic PVCs manifesting narrow
      QRS complex with qR pattern in inferior leads. The procedure of RFCA was
      performed based on pace mapping and activation mapping. RESULTS: Among the 40
      patients with narrow PVCs, complete elimination of PVCs was achieved by RFCA in
      35 patients during a median follow-up period of 23 months. Successful ablation
      was achieved on 19 patients at the sites where earliest Purkinje potentials were
      recorded in left ventricular anterosuperior septum, thus PVCs arising from left
      anterior fascicle (LAF) were confirmed, for these PVCs, the QRS morphology were
      right bundle branch and left posterior fascicle block (RBBB + LPFB) with
      rightward axis, the average QRS duration 116.07 +/- 7.96 ms, R or rsR'in lead
      V1,with transition zone ahead of lead V1 in precordial leads. Another 16
      successful RFCA were achieved by energy delivery at interleaflet triangle(ILT)
      between right coronary cusp(RCC) and left coronary cusp(LCC) where no Purkinje
      potentials were recorded, for narrow PVCs arising from the L-RCC ILT, the QRS
      morphology were similar to the PVCs arising from LAF but much narrower in QRS
      duration (100.44 +/- 3.49 vs. 116.07 +/- 7.96 ms, p < 0.05), they were also R or
      Rs in lead V1 with the transition zone ahead of lead V1. For 5 symptomatic narrow
      PVCs failed to the procedure of RFCA, their electrocardiographic characteristics
      showed that the narrowest QRS duration (91.80 +/- 6.94 vs. 100.44 +/- 3.49,
      116.07 +/- 7.96 ms, p < 0.05), rs or rS (r/s or r/S?1) morphology in lead V1 with
      the precordial transition zone behind lead V3. CONCLUSIONS: Most of idiopathic
      PVCs of narrow QRS duration (<130 msec) with qR pattern in inferior leads can be
      cured by the procedure of RFCA. On the basis of our study, we proposed that for
      narrow PVCs presenting qR pattern in inferior leads, when the ablation procedure
      failed at proximity of LAF within left anterosuperior septum, mapping and
      ablation in L-RCC ILT can be tried. The present findings can be helpful for
      planning catheter ablation for narrow PVCs manifesting qR in inferior leads.

PMID- 27044386
TI  - Regulatory and effector B cell cytokine production in patients with relapsing
      granulomatosis with polyangiitis.
AB  - BACKGROUND: B cells are capable of producing regulatory and effector cytokines.
      In patients with granulomatosis with polyangiitis (GPA), skewing of the pro- and
      anti-inflammatory cytokine balance may affect the risk of relapse. This study
      aimed to investigate differences in B cell cytokine production in patients with
      relapsing GPA and in controls, and determine whether this can aid in relapse
      prediction. METHODS: Thirteen GPA patients with an upcoming relapse were matched
      with non-relapsing patients and healthy controls in a retrospective design. The B
      cell subset distribution was determined from peripheral blood. Cryopreserved
      peripheral blood mononuclear cells were cultured and intracellular B cell
      production of regulatory (IL10) and effector (TNFalpha, IFNgamma, IL2, IL6)
      cytokines was assessed. Finally, serum markers associated with B cell activation
      (sCD27) and migration (CCL19) were determined. RESULTS: GPA patient samples
      exhibited significantly lower percentages of TNFalpha+ B cells than controls, an
      effect that was most pronounced in patients about to relapse. B cell capacity for
      IL10 production was similar in patients and controls. No significant differences
      were observed for cytokine production in relapsing and non-relapsing GPA
      patients. TNFalpha production correlated strongly with IL2, IFNgamma and the
      percentage of memory B cells. No change in effector cytokines occurred before
      relapse, while the percentage of IL10+ B cells significantly decreased. GPA
      patients in remission had increased serum levels of CCL19 and sCD27, and sCD27
      levels increased upon active disease. CONCLUSIONS: While differences in effector
      B cell cytokine production were observed between patients and controls,
      monitoring this in GPA did not clearly distinguish patients about to relapse.
      Prospective measurements of the regulatory cytokine IL10 may have potential for
      relapse prediction. Memory B cells appear mainly responsible for effector
      cytokine production. Increased migration of these cells could explain the
      decreased presence of TNFalpha+ B cells in the circulation.

PMID- 27044387
TI  - Myocardial perfusion imaging with 99mTc-labeled radiopharmaceuticals: How fast
      can a stress-rest same-day imaging protocol be completed?

PMID- 27044388
TI  - High spatial validity is not sufficient to elicit voluntary shifts of attention.
AB  - Previous research suggests that the use of valid symbolic cues is sufficient to
      elicit voluntary shifts of attention. The present study interpreted this previous
      research within a broader theoretical context which contends that observers will
      voluntarily use symbolic cues to orient their attention in space when the
      temporal costs of using the cues are perceived to be less than the temporal costs
      of searching without the aid of the cues. In this view, previous research has not
      addressed the sufficiency of valid symbolic cues, because the temporal cost of
      using the cues is usually incurred before the target display appears. To address
      this concern, 70%-valid spatial word cues were presented simultaneously with a
      search display. In addition, other research suggests that opposing cue-dependent
      and cue-independent spatial biases may operate in these studies and alter
      standard measures of orienting. After identifying and controlling these opposing
      spatial biases, the results of two experiments showed that the word cues did not
      elicit voluntary shifts of attention when the search task was relatively easy but
      did when the search task was relatively difficult. Moreover, the findings also
      showed that voluntary use of the word cues changed over the course of the
      experiment when the task was difficult, presumably because the temporal cost of
      searching without the cue lessened as the task got easier with practice.
      Altogether, the present findings suggested that the factors underlying voluntary
      control are multifaceted and contextual, and that spatial validity alone is not
      sufficient to elicit voluntary shifts of attention.

PMID- 27044389
TI  - miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR
      17 is associated with poor prognosis.
AB  - Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the
      reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently,
      MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA
      cluster that suppresses chromatin regulatory genes and the apoptosis regulator
      Bim. However, the expression and prognostic impact of miR-17-92 members in
      pediatric BL (pBL) are unknown. Therefore, we investigated miR-17, miR-19a, miR
      19b, miR-20, and miR-92a expression and prognostic impact in a series of 41 pBL
      samples. In addition, Bim protein expression was evaluated and compared to miR
      17, miR-19a, miR-19b, miR-20, and miR-92a levels and patient outcomes. The
      expression of miR-17-92 members was evaluated by qPCR and Bim protein by
      immunohistochemistry. Log-rank test was employed to assess prognostic impact. We
      found that upregulated expression of miR-17 and miR-20a correlates with lack of
      pro-apoptotic Bim expression. Patients bearing tumors with upregulated miR-17
      displayed decreased overall survival (OS), and multivariate analysis revealed
      that miR-17 was a significant predictor of shortened OS. Using hairpin
      inhibitors, we showed that inhibition of miR-17 resulted in enhanced Bim
      expression in a BL cell line overexpressing the miR-17-92 cluster. Our results
      describe for the first time miR-17, miR-19a, miR-19b, miR-20a, and miR-92a
      expression profiles in pBL. The prognostic impact of miR-17 should be validated
      in a larger series, and may provide new therapeutic avenues in the era of anti
      miRNA therapy research. Additional functional studies are further required to
      understand the specific role of miR-17-92 cluster members in BL. 

PMID- 27044390
TI  - Reduced frequency treatment with bortezomib plus dexamethasone for elderly
      patients with relapsed and/or refractory multiple myeloma: a phase 2 study of the
      Japanese Myeloma Study Group (JMSG-0902).
AB  - Bortezomib is one of the most widely used novel drugs for the treatment of
      multiple myeloma (MM). However, twice-weekly intravenous administration is
      associated with innegligible adverse events and treatment discontinuation. We
      therefore evaluated the long-term efficacy and feasibility of reduced frequency
      treatment with intravenous bortezomib in elderly patients with relapsed and/or
      refractory MM. A total of 47 bortezomib-naive patients (median age 75 years)
      received bortezomib (1.3 mg/m(2), intravenously) and dexamethasone (20 mg) on
      days 1, 8, and 15 of every 4-week cycle. Twenty-six patients completed the
      planned 8 cycles. Best responses were stringent complete response (sCR) in 5
      patients, very good partial response (VGPR) in 3, PR in 15, stable disease (SD)
      in 18, and disease progression (PD) in 6, respectively. Median progression-free
      and overall survivals were 9.6 and 35.1 months, respectively. After progression,
      11 patients were retreated with bortezomib-based regimens and another 24 patients
      with immunomodulatory drugs. Multivariate analysis revealed that ISS 3, t(4;14),
      and <4 therapy cycles were significantly poor prognostic factors and that
      subsequent therapy with bortezomib-based regimens was a favorable factor for
      extended OS. The common adverse events were diarrhea, constipation, and
      peripheral neuropathy with no grade 4 toxicity. In conclusion, reduced frequency
      treatment with intravenous bortezomib + dexamethasone is an effective option for
      elderly patients with MM. 

PMID- 27044391
TI  - Study protocol: DEcisions in health Care to Introduce or Diffuse innovations
      using Evidence (DECIDE).
AB  - BACKGROUND: A range of evidence informs healthcare decision-making, from formal
      research findings to 'soft intelligence' or local data, as well as practical
      experience or tacit knowledge. However, cultural and organisational factors often
      prevent the translation of such evidence into practice. Using a multi-level
      framework, this project will analyse how interactions between the evidence
      available and processes at the micro (individual/group) and meso
      (organisational/system) levels influence decisions to introduce or diffuse
      innovations in acute and primary care within the National Health Service in the
      UK. METHODS/DESIGN: This study will use a mixed methods design, combining
      qualitative and quantitative methods, and involves four interdependent work
      streams: (1) rapid evidence synthesis of relevant literature with stakeholder
      feedback; (2) in-depth case studies of 'real-world' decision-making in acute and
      primary care; (3) a national survey and discrete choice experiment; and (4)
      development of guidance for decision-makers and evaluators to support the use of
      evidence in decision-making. DISCUSSION: This study will enhance the
      understanding of decision-makers' use of diverse forms of evidence. The findings
      will provide insights into how and why some evidence does inform decisions to
      introduce healthcare innovations, and why barriers persist in other cases. It
      will also quantify decision-makers' preferences, including the 'tipping point' of
      evidence needed to shift stakeholders' views. Practical guidance will be shared
      with healthcare decision-makers and evaluators on uses of evidence to enable the
      introduction and diffusion of innovation.

PMID- 27044392
TI  - Surgical treatment for pelvic giant cell tumor: a multi-center study.
AB  - BACKGROUND: The purpose of this study was to discuss the clinical results which
      related to the location of giant cell tumors (GCTs) in the pelvis so as to
      determine the ideal surgical treatment protocol. METHODS: We report 29 cases who
      accepted surgical treatment from five clinical centers during the last 12 years.
      All patients were divided into three groups according to tumor locations, and
      they were also classified into two groups in light of surgical treatments. The
      parameters for outcome evaluation consisting of general condition, surgical
      complications, local disease control, and Musculoskeletal Tumor Society (MSTS) 93
      functional score had been analyzed, respectively. RESULTS: Surgical treatment in
      the acetabular area usually resulted in postoperative complications and poor
      function. One patient who accepted intralesional surgery and two who accepted
      wide resection had local recurrence. The mean functional score was 25.4 for the 8
      patients who received intralesional surgery and 21.9 for the 21 patients who
      received wide resection. Surgical complications occurred in 1 patient who
      underwent intralesional surgery and the other 6 patients who underwent wide
      resection. CONCLUSIONS: We conclude that surgical treatment of pelvic GCTs in the
      acetabular area is difficult to select as it is always accompanied by
      complications and poor function. Compared to wide resection, intralesional
      surgery combined with a meticulous preoperative planning may lower the recurrence
      rate and obtain favorable postoperative functional results.

PMID- 27044393
TI  - Combined effects of sleep quality and depression on quality of life in patients
      with type 2 diabetes.
AB  - BACKGROUND: Poor sleep quality and depression negatively impact the health
      related quality of life of patients with type 2 diabetes, but the combined effect
      of the two factors is unknown. This study aimed to assess the interactive effects
      of poor sleep quality and depression on the quality of life in patients with type
      2 diabetes. METHODS: Patients with type 2 diabetes (n = 944) completed the
      Diabetes Specificity Quality of Life scale (DSQL) and questionnaires on sleep
      quality and depression. The products of poor sleep quality and depression were
      added to the logistic regression model to evaluate their multiplicative
      interactions, which were expressed as the relative excess risk of interaction
      (RERI), the attributable proportion (AP) of interaction, and the synergy index
      (S). RESULTS: Poor sleep quality and depressive symptoms both increased DSQL
      scores. The co-presence of poor sleep quality and depressive symptoms
      significantly reduced DSQL scores by a factor of 3.96 on biological interaction
      measures. The relative excess risk of interaction was 1.08. The combined effect
      of poor sleep quality and depressive symptoms was observed only in women.
      CONCLUSIONS: Patients with both depressive symptoms and poor sleep quality are at
      an increased risk of reduction in diabetes-related quality of life, and this risk
      is particularly high for women due to the interaction effect. Clinicians should
      screen for and treat sleep difficulties and depressive symptoms in patients with
      type 2 diabetes.

PMID- 27044394
TI  - Heritability of Wing Size and Shape of the Rice and Corn Strains of Spodoptera
      frugiperda (J.E. Smith) (Lepidoptera: Noctuidae).
AB  - Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) represents a pest of
      economic importance in all Western Hemisphere. This polyphagous species has
      diverged into two populations that have been mainly recognized with various
      mitochondrial and nuclear molecular markers and named "the rice" and "the corn"
      strains. In Colombia, both strains have evolved prezygotic and postzygotic
      isolation. They differ in tolerance to Bacillus thuringiensis (Cry1Ac and Cry1Ab
      endotoxins) and the insecticides lambda-cyhalothrin and methomyl. In 2014, a wing
      morphometric analysis made in 159 individuals from a colony showed that both
      strains significantly differ in wing shape. The species also exhibits sexual
      dimorphism in the rice strain as in females wing size is larger than in males.
      Here, we continued this work with another wing morphometric approach in
      laboratory-reared strains to calculate wing size and shape heritabilities using a
      full-sib design and in wild populations to determine if this method distinguishes
      these strains. Our results show that male heritabilities of both traits were
      higher than female ones. Wild populations were significantly different in wing
      shape and size. These results suggest that wing morphometrics can be used as an
      alternative method to molecular markers to differentiate adults from laboratory
      reared populations and wild populations of this pest, particularly in males of
      this species. Finally, Q ST values obtained for wing size and shape further
      demonstrated that both strains are genetically differentiated in nature. 

PMID- 27044395
TI  - From osteoarthritic synovium to synovial-derived cells characterization: synovial
      macrophages are key effector cells.
AB  - BACKGROUND: The aim of the study was to characterize synovial cells from OA
      synovium with low-grade and moderate-grade synovitis and to define the role of
      synovial macrophages in cell culture. METHODS: Synovial tissue explants were
      analyzed for the expression of typical markers of synovial fibroblasts (SF),
      synovial macrophages (SM) and endothelial cells. Synovial cells at passage 1
      (p.1) and 5 (p.5) were analyzed for different phenotypical markers by flow
      cytometric analysis, inflammatory factors by multiplex immunoassay, anabolic and
      degradative factors by qRT-PCR. P.1 and p.5 synovial cells as different cell
      models were co-cultured with adipose stem cells (ASC) to define SM effects.
      RESULTS: Synovial tissue showed a higher percentage of CD68 marker in moderate
      compared with low-grade synovitis. Isolated synovial cells at p.1 were positive
      to typical markers of SM (CD14, CD16, CD68, CD80 and CD163) and SF (CD55, CD73,
      CD90, CD105, CD106), whereas p.5 synovial cells were positive only to SF markers
      and showed a higher percentage of CD55 and CD106. At p.1 synovial cells released
      a significantly higher amount of all inflammatory (IL6, CXCL8, CCL2, CCL3, CCL5)
      and some anabolic (IL10) factors than those of p.5. Moreover, p.1 synovial cells
      also expressed a higher amount of some degradative factors (MMP13, S100A8,
      S100A9) than p.5 synovial cells. Co-culture experiments showed that the amount of
      SM in p.1 synovial cells differently induced or down-modulated some of the
      inflammatory (IL6, CXCL8, CCL2, CCL3, CCL5) and degradative factors (ADAMTS5,
      MMP13, S100A8, S100A9). CONCLUSIONS: We found that p.1 (mix of SM and SF) and p.5
      (only SF) synovial cells represent two cell models that effectively reproduce the
      low- or moderate-grade synovitis environment. The presence of SM in culture
      specifically induces the modulation of the different factors analyzed, confirming
      that SM are key effector cells.

PMID- 27044396
TI  - Managing critically ill patients with severe traumatic brain injury: How should
      we season the recipe?

PMID- 27044397
TI  - Spinal prilocaine for same-day surgery: the importance of equipotent doses.

PMID- 27044398
TI  - The alignment approach to nasotracheal intubation.

PMID- 27044399
TI  - Curriculum reform for residency training: competence, change, and opportunities
      for leadership.
AB  - PURPOSE: Certain pressures stemming from within the medical community and from
      society in general, such as the need for increased accountability in resident
      training and restricted resident duty hours, have prompted a re-examination of
      methods for training physicians. Leaders in medical education in North America
      and around the world champion competency-based medical education (CBME) as a
      solution. The Department of Anesthesiology at the University of Ottawa launched
      Canada's first CBME program for anesthesiology residents on July 1, 2015. In this
      paper, we discuss the opportunities and challenges associated with CBME and
      delineate the elements of the new CBME program at the University of Ottawa.
      SOURCE: Review of the current literature. PRINCIPAL FINDINGS: Competency-based
      medical education addresses some of the challenges associated with physician
      training, such as ensuring that specialists are competent in all key areas and
      reducing training costs. In principle, competency-based medical education can
      better meet the needs of patients, providers, and other stakeholders in the
      healthcare system, but its success will depend on support from all involved. As
      CBME is implemented, anesthesiologists have the opportunity to become leaders in
      innovation and medical education. The University of Ottawa has implemented a CBME
      program with a twofold purpose, namely, to focus learning opportunities on the
      development of the specific competencies required of practicing anesthesiologists
      and to test the effectiveness of a reduction in the length of training.
      CONCLUSION: Canadian anesthesia residency programs will soon transition to CBME
      in order to promote better transparency, accountability, fairness, fiscal
      responsibility, and patient safety. Competency-based medical education offers
      significant potential advantages for healthcare stakeholders.

PMID- 27044400
TI  - Hospital-based health technology assessment (HTA) in Finland: a case study on
      collaboration between hospitals and the national HTA unit.
AB  - BACKGROUND: This study examines, as a part of the European Union funded Adopting
      Hospital Based Health Technology Assessment (AdHopHTA) project, the results and
      barriers of collaboration between Finnish hospitals and the national health
      technology assessment (HTA) agency, Finohta. A joint collaborative HTA program
      has existed since 2006 between the Finnish hospitals and the national agency.
      METHODS: A case study method was used. Information about the collaboration
      between Finnish hospitals and Finohta was retrieved from interviews and
      publications, and categorised per theme. Hypotheses and indicators of successful
      collaboration were determined beforehand and reflected on the observations from
      the interviews and literature. RESULTS: Overall, 48 collaborative HTA reports
      have been performed during 7 years of collaboration. However, there were no clear
      indications that the use of HTA information or the transparency of decision
      making regarding new technologies would have increased in hospitals. The
      managerial commitment to incorporate HTAs into the decision-making processes in
      hospitals was still low. The quality of the collaborative HTA reports was
      considered good, but their applicability in the hospital setting limited. There
      were differing expectations about the timing and relevance of the content. Signs
      of role conflict and mistrust were observed. CONCLUSIONS: Despite collaborative
      efforts to produce HTAs for hospitals, the impact of HTA information on hospital
      decision-making appears to remain low. The difficulties identified in this case
      study, such as lack of managerial commitment in hospitals, can hopefully be
      better addressed in the future with the guidance and tools having been developed
      in the AdHopHTA project. Collaboration between hospitals and national HTA
      agencies remains important for the efficient sharing of skills and resources.

PMID- 27044401
TI  - Understanding the implementation of interventions to improve the management of
      chronic kidney disease in primary care: a rapid realist review.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common and a significant marker of
      morbidity and mortality. Its management in primary care is essential for
      maintenance of cardiovascular health, avoidance of acute kidney injury (AKI) and
      delay in progression to end-stage renal disease. Although many guidelines and
      interventions have been established, there is global evidence of an
      implementation gap, including variable identification rates and low patient
      communication and awareness. The objective of this study is to understand the
      factors enabling and constraining the implementation of CKD interventions in
      primary care. METHODS: A rapid realist review was conducted that involved a
      primary literature search of three databases to identify existing CKD
      interventions in primary care between the years 2000 and 2014. A secondary search
      was performed as an iterative process and included bibliographic and grey
      literature searches of reference lists, authors and research groups. A systematic
      approach to data extraction using Normalisation Process Theory (NPT) illuminated
      key mechanisms and contextual factors that affected implementation. RESULTS: Our
      primary search returned 710 articles that were narrowed down to 18 relevant CKD
      interventions in primary care. Our findings suggested that effective management
      of resources (encompassing many types) was a significant contextual factor
      enabling or constraining the functioning of mechanisms. Three key intervention
      features were identified from the many that contributed to successful
      implementation. Firstly, it was important to frame CKD interventions
      appropriately, such as within the context of cardiovascular health and diabetes.
      This enabled buy-in and facilitated an understanding of the significance of CKD
      and the need for intervention. Secondly, interventions that were compatible with
      existing practices or patients' everyday lives were readily accepted. In
      contrast, new systems that could not be integrated were abandoned as they were
      viewed as inconvenient, generating more work. Thirdly, ownership of the feedback
      process allowed users to make individualised improvements to the intervention to
      suit their needs. CONCLUSIONS: Our rapid realist review identified mechanisms
      that need to be considered in order to optimise the implementation of
      interventions to improve the management of CKD in primary care. Further research
      into the factors that enable prolonged sustainability and cost-effectiveness is
      required for efficient resource utilisation.

PMID- 27044402
TI  - Implementation of baby boomer hepatitis C screening and linking to care in
      gastroenterology practices: a multi-center pilot study.
AB  - BACKGROUND: Estimates suggest that only 20 % of HCV-infected patients have been
      identified and <10 % treated. However, baby boomers (1945-1965) are identified as
      having a higher prevalence of HCV which has led the Centers for Disease Control
      and Prevention to make screening recommendations. The aim of this study was to
      implement the CDC's screening recommendations in the unique setting of
      gastroenterology practices in patients previously unscreened for HCV. METHODS:
      After obtaining patient informed consent, demographics, clinical and health
      related quality of life (HRQOL) data were collected. A blood sample was screened
      for HCV antibody (HCV AB) using the OraQuick HCV Rapid Antibody Test. HCV AB
      positive patients were tested for presence of HCV RNA and, if HCV RNA positive,
      patients underwent treatment discussions. RESULTS: We screened 2,000 individuals
      in 5 gastroenterology centers located close to large metropolitan areas on the
      East Coast (3 Northeast, 1 Mid-Atlantic and 1 Southeast). Of the screened
      population, 10 individuals (0.5 %) were HCV AB-positive. HCV RNA testing was
      performed in 90 % (9/10) of HCV AB-positive individuals. Of those, 44.4 % (4/9)
      were HCV RNA-positive, and all 4 (100 %) were linked to caregiver. Compared to
      HCV AB negative subjects, HCV AB-positive individuals tended to be black (20.0
      vs. 5.2 %, p = 0.09) and reported significantly higher rates of depression: 60.0
      vs. 21.5 %, p = 0.009. These individuals also reported a significantly lower
      HRQOL citing having more fatigue, poorer concentration, and a decreased level of
      energy (p < 0.05). DISCUSSION: Although the prevalence of HCV AB-positive was low
      in previously unscreened subjects screened in the gastroenterology centers, the
      linkage to care was very high. The sample of patients used in this study may be
      biased, so further studies are needed to assess the effectiveness of the CDC
      screening recommendations. CONCLUSION: Implementation of the Baby Boomer
      Screening for HCV requires identifying screening environement with high
      prevalence of HCV+ individuals as well as an efficient process of linking them to
      care.

PMID- 27044403
TI  - Is adjuvant chemotherapy necessary for patients with pathological complete
      response after neoadjuvant chemoradiotherapy and radical surgery in locally
      advanced rectal cancer? Long-term analysis of 40 ypCR patients at a single
      center.
AB  - OBJECTIVES: According to practice guidelines, adjuvant chemotherapy (ACT) is
      required for all patients with locally advanced rectal cancer who have received
      neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The
      objective of this study was to determine whether ACT is necessary for patients
      achieving pathological complete response (pCR) after NCRT followed by surgery.
      METHODS: By retrospectively reviewing a prospectively collected database in our
      single tertiary care center, 210 patients with locally advanced rectal cancer who
      underwent NCRT followed by TME were identified between February 2005 and August
      2013. All patients achieving ypCR were enrolled in this study, in which who
      underwent ACT (chemo group) and who did not (non-chemo group) were compared in
      terms of local recurrence (LR) rate, 5-year disease-free survival (DFS) rate and
      overall survival (OS) rate. RESULTS: Forty consecutive patients with ypCR were
      enrolled, 19 (47.5 %) in chemo group and 21 (52.5 %) in non-chemo group. After a
      median follow-up of 57 months, five patients developed systemic recurrences, with
      the 5y-DFS rate of 83.5 %. No LR occurred in the two groups. The 5y-DFS rates for
      patients in chemo group and non-chemo group was 90.9 and 76.0 %, respectively,
      showing no statistically significant difference (p = 0.142). Multivariate
      analysis showed that tumor grade was the only independent prognostic factor for
      5y-DFS and 5y-OS. CONCLUSIONS: Results of this study suggested that it may not be
      necessary for all rectal cancer patients with ypCR after NCRT and radical surgery
      to receive ACT. Prospective randomized trials are warranted to further determine
      the value of ACT for ypCR patients.

PMID- 27044404
TI  - Clinical relevance of the tumor microenvironment and immune escape of oral
      squamous cell carcinoma.
AB  - BACKGROUND: Changes in the tumor microenvironment and immune surveillance
      represent crucial hallmarks of various kinds of cancer, including oral squamous
      cell carcinoma (OSCC), and a close crosstalk of hypoxia regulating genes, an
      activation of chemokines and immune cells has been described. METHODS: A review
      about the pivotal role of HIF-1, its crosstalk to various cornerstones in OSCC
      tumorigenesis is presented. RESULTS: Hypoxia is a frequent event in OSCC and
      leads to a reprogramming of the cellular metabolism in order to prevent cell
      death. Hypoxic OSCC cells induce different adaptive changes such as anaerobic
      glycolysis, pH stabilisation and alterations of the gene and protein expression
      profile. This complex metabolic program is orchestrated by the hypoxia inducible
      factor (HIF)-1, the master regulator of early tumor progression. Hypoxia
      dependent and -independent alterations in immune surveillance lead to different
      immune evasion strategies, which are partially mediated by alterations of the
      tumor cells, changes in the frequency, activity and repertoire of immune cell
      infiltrates and of soluble and environmental factors of the tumor micromilieu
      with consecutive generation of an immune escape phenotype, progression of disease
      and poor clinical outcome of OSCC patients. CONCLUSIONS: This review focusses on
      the importance of HIF-1 in the adaption and reprogramming of the metabolic system
      to reduced oxygen values as well as on the role of the tumor microenvironment for
      evasion of OSCC from immune recognition and destruction.

PMID- 27044405
TI  - Regnase-1 in microglia negatively regulates high mobility group box 1-mediated
      inflammation and neuronal injury.
AB  - Extracellular high mobility group box 1 (HMGB1) has been demonstrated to function
      as a proinflammatory cytokine and induces neuronal injury in response to various
      pathological stimuli in central nervous system (CNS). However, the regulatory
      factor involved in HMGB1-mediated inflammatory signaling is largely unclear.
      Regulatory RNase 1 (Regnase-1) is a potent anti-inflammation enzyme that can
      degrade a set of mRNAs encoding proinflammatory cytokines. The present study aims
      to determine the role of Regnase-1 in the regulation of HMGB1-mediated
      inflammatory injury in CNS. Cultured microglia and rat brain were treated with
      recombinant HMGB1 to examine the induction of Regnase-1 expression. Moreover, the
      role of Regnase-1 in modulating the expression of inflammatory cytokines and
      neuronal injury was then investigated in microglia by specific siRNA knockdown
      upon HMGB1 treatment. Results showed that HMGB1 could significantly induce the de
      novo synthesis of Regnase-1 in cultured microglia. Consistently, Regnase-1 was
      elevated and found to be co-localized with microglia marker in the brain of rat
      treated with HMGB1. Silencing Regnase-1 in microglia enhanced HMGB1-induced
      expression of proinflammatory cytokines and exacerbated neuronal toxicity.
      Collectively, these results suggest that Regnase-1 can be induced by HMGB1 in
      microglia and negatively regulates HMGB1-mediated neuroinflammation and neuronal
      toxicity. 

PMID- 27044406
TI  - Clinical Features and Outcomes of Diffuse Alveolar Hemorrhage During
      Antithrombotic Therapy: A Retrospective Cohort Study.
AB  - PURPOSE: Antithrombotic therapy could trigger diffuse alveolar hemorrhage (DAH),
      and there are several case reports of DAH that occurred during antithrombotic
      therapy (DAH-AT). However, little is known about the clinical features and
      outcomes of DAH-AT. The purpose of this study was to clarify the features and
      mortality of DAH-AT. METHODS: 76 consecutive patients with DAH who were admitted
      to our hospital between January 2003 and April 2014 were retrospectively reviewed
      to identify the clinical features and outcomes of DAH-AT. The primary outcome was
      90-day mortality. RESULTS: Of the 76 patients with DAH, 39 patients (51 %) had
      DAH-AT, and 37 patients (49 %) had DAH that occurred with no antithrombotic
      therapy (DAH-NAT). Of the patients with DAH-AT, 25 (64 %) were taking aspirin, 14
      (36 %) were taking warfarin, 5 (13 %) were taking clopidogrel sulfate, and 4 (10
      %) were taking cilostazol. Pre-existing cardiac disease was present in 23 (59 %)
      DAH-AT cases and 5 (14 %) DAH-NAT cases. Logistic regression analysis was used to
      assess the effect of antithrombotic therapy on the mortality of DAH patients, and
      no significant difference in survival was seen with antithrombotic therapy (OR
      1.18, 95 % CI 0.38-3.78). CONCLUSIONS: Antithrombotic therapies had no effect on
      the 90-day mortality of DAH patients.

PMID- 27044407
TI  - Successfully Implementing Schwartz Center Rounds(r) Within an Adult Psychiatric
      Hospital.

PMID- 27044408
TI  - Transforming Frustration into Possibility: A Model for Understanding and
      Navigating Complex Systems in a Changing Landscape.

PMID- 27044409
TI  - Diminution of the gut resistome after a gut microbiota-targeted dietary
      intervention in obese children.
AB  - The gut microbiome represents an important reservoir of antibiotic resistance
      genes (ARGs). Effective methods are urgently needed for managing the gut
      resistome to fight against the antibiotic resistance threat. In this study, we
      show that a gut microbiota-targeted dietary intervention, which shifts the
      dominant fermentation of gut bacteria from protein to carbohydrate, significantly
      diminished the gut resistome and alleviated metabolic syndrome in obese children.
      Of the non-redundant metagenomic gene catalog of ~2 * 10(6) microbial genes, 399
      ARGs were identified in 131 gene types and conferred resistance to 47
      antibiotics. Both the richness and diversity of the gut resistome were
      significantly reduced after the intervention. A total of 201 of the 399 ARGs were
      carried in 120 co-abundance gene groups (CAGs) directly binned from the gene
      catalog across both pre-and post-intervention samples. The intervention
      significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia,
      which were the major hubs for multiple resistance gene types. Thus, dietary
      intervention may become a potentially effective method for diminishing the gut
      resistome.

PMID- 27044410
TI  - Optimization of brain PET imaging for a multicentre trial: the French CATI
      experience.
AB  - BACKGROUND: CATI is a French initiative launched in 2010 to handle the
      neuroimaging of a large cohort of subjects recruited for an Alzheimer's research
      program called MEMENTO. This paper presents our test protocol and results
      obtained for the 22 PET centres (overall 13 different scanners) involved in the
      MEMENTO cohort. We determined acquisition parameters using phantom experiments
      prior to patient studies, with the aim of optimizing PET quantitative values to
      the highest possible per site, while reducing, if possible, variability across
      centres. METHODS: Jaszczak's and 3D-Hoffman's phantom measurements were used to
      assess image spatial resolution (ISR), recovery coefficients (RC) in hot and cold
      spheres, and signal-to-noise ratio (SNR). For each centre, the optimal
      reconstruction parameters were chosen as those maximizing ISR and RC without a
      noticeable decrease in SNR. Point-spread-function (PSF) modelling reconstructions
      were discarded. The three figures of merit extracted from the images
      reconstructed with optimized parameters and routine schemes were compared, as
      were volumes of interest ratios extracted from Hoffman acquisitions. The net
      effect of the 3D-OSEM reconstruction parameter optimization was investigated on a
      subset of 18 scanners without PSF modelling reconstruction. RESULTS: Compared to
      the routine parameters of the 22 PET centres, average RC in the two smallest hot
      and cold spheres and average ISR remained stable or were improved with the
      optimized reconstruction, at the expense of slight SNR degradation, while the
      dispersion of values was reduced. For the subset of scanners without PSF
      modelling, the mean RC of the smallest hot sphere obtained with the optimized
      reconstruction was significantly higher than with routine reconstruction. The
      putamen and caudate-to-white matter ratios measured on 3D-Hoffman acquisitions of
      all centres were also significantly improved by the optimization, while the
      variance was reduced. CONCLUSIONS: This study provides guidelines for optimizing
      quantitative results for multicentric PET neuroimaging trials.

PMID- 27044411
TI  - Understanding the Impact of Electronic Medical Record Use on Practice-Based
      Population Health Management: A Mixed-Method Study.
AB  - BACKGROUND: Practice-based population health (PBPH) management is the proactive
      management of patients by their primary care clinical team. The ability of
      clinics to engage in PBPH and the means by which they incorporate it in a
      clinical setting remain unknown. OBJECTIVE: We conducted the Canadian Population
      Health Management Challenge to determine the capacity and preparedness of primary
      care settings to engage in PBPH using their existing medical record systems and
      to understand the complexities that may exist in PBPH implementation. METHODS: We
      recruited a sample of electronic medical record (EMR) -enabled and paper-based
      clinics from across Canada to participate in the challenge. The challenge
      required clinic staff and physicians to complete time-controlled, evidence-based
      practice reviews of their patients who may benefit from evidence-informed care,
      treatment, or interventions across five different areas (immunization,
      postmyocardial infarction care, cancer screening, diabetes management, and
      medication recall). We formulated a preparedness index to measure the capacity of
      clinics to engage in PBPH management. Finally, we conducted follow-up qualitative
      interviews to provide richer understanding of PBPH implementation and related
      issues (ie, challenges and facilitators). RESULTS: A total of 11 primary care
      clinics participated, representing 21 clinician practices. EMR-enabled clinics
      completed a full review of charts in an average of 1.37 hours. On the contrary,
      paper-based clinics reviewed nearly 10% of their charts in an average of 3.9
      hours, hinting that they would have required an estimated 40 hours to complete a
      review of charts in their practice. Furthermore, the index revealed a major gap
      in preparedness between the EMR and paper-based clinics (0.86-3.78 vs 0.05-0.12),
      as well as a broad range among the EMR clinics. Finally, building on the results
      of the qualitative analysis, we identified factors facilitating the integration
      of PBPH. CONCLUSIONS: Our results suggest that EMR usage is pivotal in setting
      the foundation to support PBPH. The wide range of performance variation among EMR
      enabled clinics suggests that EMR functionality and optimization, its support of
      clinical practice workflow, and policy issues to ensure adoption of standards are
      critical issues to facilitate PBPH.

PMID- 27044412
TI  - A pure chloride channel mutant of CLC-5 causes Dent's disease via insufficient V
      ATPase activation.
AB  - Dent's disease is characterized by defective endocytosis in renal proximal
      tubules (PTs) and caused by mutations in the 2Cl(-)/H(+) exchanger, CLC-5.
      However, the pathological role of endosomal acidification in endocytosis has
      recently come into question. To clarify the mechanism of pathogenesis for Dent's
      disease, we examined the effects of a novel gating glutamate mutation, E211Q, on
      CLC-5 functions and endosomal acidification. In Xenopus oocytes, wild-type (WT)
      CLC-5 showed outward-rectifying currents that were inhibited by extracellular
      acidosis, but E211Q and an artificial pure Cl(-) channel mutant, E211A, showed
      linear currents that were insensitive to extracellular acidosis. Moreover,
      depolarizing pulse trains induced a robust reduction in the surface pH of oocytes
      expressing WT CLC-5 but not E211Q or E211A, indicating that the E211Q mutant
      functions as a pure Cl(-) channel similar to E211A. In HEK293 cells, E211A and
      E211Q stimulated endosomal acidification and hypotonicity-inducible vacuolar-type
      H(+)-ATPase (V-ATPase) activation at the plasma membrane. However, the
      stimulatory effects of these mutants were reduced compared with WT CLC-5.
      Furthermore, gene silencing experiments confirmed the functional coupling between
      V-ATPase and CLC-5 at the plasma membrane of isolated mouse PTs. These results
      reveal for the first time that the conversion of CLC-5 from a 2Cl(-)/H(+)
      exchanger into a Cl(-) channel induces Dent's disease in humans. In addition,
      defective endosomal acidification as a result of insufficient V-ATPase activation
      may still be important in the pathogenesis of Dent's disease.

PMID- 27044413
TI  - Retrotransposon-associated long non-coding RNAs in mice and men.
AB  - Over a half of mammalian genomes is occupied by repetitive elements whose ability
      to provide functional sequences, move into new locations, and recombine underlies
      the so-called genome plasticity. At the same time, mobile elements exemplify
      selfish DNA, which is expanding in the genome at the expense of the host. The
      selfish generosity of mobile genetic elements is in the center of research
      interest as it offers insights into mechanisms underlying evolution and emergence
      of new genes. In terms of numbers, with over 20,000 in count, protein-coding
      genes make an outstanding >2 % minority. This number is exceeded by an ever
      growing list of genes producing long non-coding RNAs (lncRNAs), which do not
      encode for proteins. LncRNAs are a dynamically evolving population of genes.
      While it is not yet clear what fraction of lncRNAs represents functionally
      important ones, their features imply that many lncRNAs emerge at random as new
      non-functional elements whose functionality is acquired through natural
      selection. Here, we explore the intersection of worlds of mobile genetic elements
      (particularly retrotransposons) and lncRNAs. In addition to summarizing essential
      features of mobile elements and lncRNAs, we focus on how retrotransposons
      contribute to lncRNA evolution, structure, and function in mammals.

PMID- 27044414
TI  - Pubertal development and prostate cancer risk: Mendelian randomization study in a
      population-based cohort.
AB  - BACKGROUND: Epidemiological studies have observed a positive association between
      an earlier age at sexual development and prostate cancer, but markers of sexual
      maturation in boys are imprecise and observational estimates are likely to suffer
      from a degree of uncontrolled confounding. To obtain causal estimates, we
      examined the role of pubertal development in prostate cancer using genetic
      polymorphisms associated with Tanner stage in adolescent boys in a Mendelian
      randomization (MR) approach. METHODS: We derived a weighted genetic risk score
      for pubertal development, combining 13 SNPs associated with male Tanner stage. A
      higher score indicated a later puberty onset. We examined the association of this
      score with prostate cancer risk, stage and grade in the UK-based ProtecT case
      control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a
      replication sample. RESULTS: In ProtecT, the puberty genetic score was inversely
      associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade
      cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental
      variable estimation of the causal OR, later physical development in adolescence
      (equivalent to a difference of one Tanner stage between pubertal boys of the same
      age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason
      prostate cancer. In PRACTICAL, the puberty genetic score was associated with
      prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95
      % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst
      cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade.
      CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk
      of later prostate cancer, especially aggressive disease.

PMID- 27044415
TI  - Epidemiology and public health significance of Cryptosporidium isolated from
      cattle, buffaloes, and humans in Egypt.
AB  - The epidemiology and public health significance of Cryptosporidium species and
      genotypes were investigated in Beni-Suef Governorate, Egypt. A total of 610
      animal fecal samples (480 from cattle and 130 from buffaloes) beside 290 stool
      samples from humans were collected in the period between January and December
      2014. Based on the microscopic examination, the overall estimated prevalence of
      Cryptosporidium spp. in cattle, buffaloes, and humans was 10.2, 12.3, and 19 %,
      respectively. The highest detection rates were in calves less than 2 months of
      age (17.1 %) and diarrheic animals (13.0 %). Likewise in humans, the highest
      prevalence of Cryptosporidium was in infants (31.3 %) and diarrheic individuals
      (21.1 %). The gender distribution in humans denoted that Cryptosporidium was
      reported more frequently in males (21.7 %) than females (14.5 %). Based on the
      molecular characterization of Cryptosporidium, Cryptosporidium oocyst wall
      protein (COWP) and gp60 genes were successfully amplified in 36 out of 50 samples
      subjected to genotyping. Restriction fragment length polymorphism (RFLP) analysis
      of the COWP fragments revealed that Cryptosporidium parvum was the only species
      detected in cattle (12 isolates) and buffaloes (4 isolates), while in humans, the
      detected species were Cryptosporidium hominis (15 isolates) and C. parvum (5
      isolates). Sequence analysis of the gp60 gene identified the subtype IIdA20G1
      within C. parvum isolated from both animals and humans. The common occurrence of
      zoonotic subtypes of C. parvum in cattle and buffaloes highlights the potential
      role of these animals as significant reservoirs of infection to humans. Also, the
      presence of C. hominis and C. parvum in humans indicates that both anthroponotic
      and zoonotic pathways are expected. 

PMID- 27044416
TI  - Distribution of energy intake throughout the day and weight gain: a population
      based cohort study in Spain.
AB  - Experimental research suggests that food timing is associated with weight
      regulation. However, the association between the distribution of energy intake
      (EI) throughout the day and weight gain in the population is uncertain. A cohort
      of 4243 individuals (49.9 % men, 50.1 % women) aged >=18 years was selected in
      2008-2010 and followed-up through 2012. At baseline, food consumption for a
      typical week in the previous year was collected with a validated dietary history,
      and EI was assessed at six eating occasions: breakfast, mid-morning meal, lunch,
      mid-afternoon meal, dinner and snacking (at any other moment). Individuals were
      classified into sex-specific quartiles of %EI for each eating occasion. The cut
      off points for increasing quartiles of %EI at lunch were 34.4, 40.8 and 47.7 % in
      men and 33.2, 39.4 and 46.1 % in women. Weight was self-reported at baseline and
      at the end of follow-up. During a 3.5-year follow-up, 16.3 % of study
      participants gained >3 kg. Compared with those in the lowest quartile of %EI at
      lunch, the multivariate OR of gaining >3 kg was 0.79 (95 % CI 0.63, 0.99) in the
      second quartile, 0.82 (95 % CI 0.64, 1.04) in the third quartile and 0.62 (95 %
      CI 0.47, 0.80) in the highest quartile (P trend: 0.001). The association was
      stronger among women and those with overweight or obesity. No association was
      found between the %EI at the rest of the eating occasions and weight gain. In
      conclusion, a higher %EI at lunch was associated with a lower risk of weight
      gain; this may help weight control through the appropriate distribution of daily
      EI.

PMID- 27044417
TI  - Exploring psychosocial interventions for people with dementia that enhance
      personhood and relate to legacy- an integrative review.
AB  - BACKGROUND: Epidemiological predictions suggest that dementia will continue to
      rise and that this will have social and economic ramifications. Effective
      interventions, beyond pharmacological management are needed. Psychosocial
      interventions have largely been investigated in relation to carers of people with
      dementia, or with regards to their ability to manage dementia symptoms, improve
      cognition, and reduce challenging behaviour. However, since dementia is a life
      limiting illness and people with dementia are at risk of having their personhood
      compromised, psychosocial interventions should seek to enhance personhood, and
      offer the potential for the person to leave a legacy. METHODS: An integrative
      review was carried out to identify, assess, appraise and synthesise studies
      featuring interventions, which relate to both personhood and legacy. Search
      strategies were developed in key databases: MEDLINE; PsycINFO; Embase; Joanna
      Briggs Institute; CINAHL; Cochrane Database of Systematic Reviews; ASSIA. Grey
      literature was also identified through free-text searches. RESULTS: Thirty six
      articles were included in the final review, these were tabulated and were
      assessed based on how the intervention related to personhood and legacy.
      Classification resulted in three themes being identified: Offering aspects of
      legacy; Acknowledging the person behind the patient; Facilitating meaningful
      engagement. Generally, personhood aspects of interventions were well reported,
      but further research is required to explore legacy potential of psychosocial
      interventions for people with dementia. CONCLUSION: The integrative review
      provides an overview and exploration of an under-researched area, and provides
      directions for future research, which will help expand the evidence base and
      ultimately help improve patient care for people with dementia and their families.

PMID- 27044418
TI  - Quantification of the smoking-associated cancer risk with rate advancement
      periods: meta-analysis of individual participant data from cohorts of the CHANCES
      consortium.
AB  - BACKGROUND: Smoking is the most important individual risk factor for many cancer
      sites but its association with breast and prostate cancer is not entirely clear.
      Rate advancement periods (RAPs) may enhance communication of smoking related risk
      to the general population. Thus, we estimated RAPs for the association of smoking
      exposure (smoking status, time since smoking cessation, smoking intensity, and
      duration) with total and site-specific (lung, breast, colorectal, prostate,
      gastric, head and neck, and pancreatic) cancer incidence and mortality. METHODS:
      This is a meta-analysis of 19 population-based prospective cohort studies with
      individual participant data for 897,021 European and American adults. For each
      cohort we calculated hazard ratios (HRs) for the association of smoking exposure
      with cancer outcomes using Cox regression adjusted for a common set of the most
      important potential confounding variables. RAPs (in years) were calculated as the
      ratio of the logarithms of the HRs for a given smoking exposure variable and age.
      Meta-analyses were employed to summarize cohort-specific HRs and RAPs. RESULTS:
      Overall, 140,205 subjects had a first incident cancer, and 53,164 died from
      cancer, during an average follow-up of 12 years. Current smoking advanced the
      overall risk of developing and dying from cancer by eight and ten years,
      respectively, compared with never smokers. The greatest advancements in cancer
      risk and mortality were seen for lung cancer and the least for breast cancer.
      Smoking cessation was statistically significantly associated with delays in the
      risk of cancer development and mortality compared with continued smoking.
      CONCLUSIONS: This investigation shows that smoking, even among older adults,
      considerably advances, and cessation delays, the risk of developing and dying
      from cancer. These findings may be helpful in more effectively communicating the
      harmful effects of smoking and the beneficial effect of smoking cessation.

PMID- 27044419
TI  - Computer-aided flapless implant surgery and immediate loading. A technical note.
AB  - PURPOSE: The aim of the present technical note was to describe a prosthetic
      technique developed to increase the predictability of immediately loaded implants
      supporting a fixed prosthesis after computer-aided template-guided flapless
      implant placement. METHODS: During a 2-year period, eight patients presenting
      partial edentulism underwent computer-aided template-guided implant placement.
      The presented technique was used during the prosthetic procedures to directly
      transfer the data obtained with the facebow to the surgical environment, allowing
      for accurate repositioning of the temporary prosthesis on the implants as
      previously planned with the digital software. RESULTS: A total of 78 dental
      implants were immediately loaded with an implant-supported fixed prosthesis after
      flapless template-guided implant placement. A survival and success rate of 100 %
      was reported after a mean follow-up of 1 year from the prosthetic loading.
      Neither major complications nor dropouts were observed during the healing time.
      From both clinical and radiological evaluations, implants appeared stable with no
      signs of soft tissue inflammation or infection and no evidence of pathological
      peri-implant bone resorption. CONCLUSIONS: The proposed technique associated with
      computer-aided implant placement and immediate loading protocol provided a high
      implant and prosthetic survival and success rate. No complications were reported
      during the recalls, suggesting predictability and reliability of the present
      technique over a short-term period.

PMID- 27044420
TI  - Pelvic retroperitoneal pleomorphic hyalinizing angiectatic tumor (PHAT) of soft
      tissue: a case report.
AB  - BACKGROUND: Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare soft
      tissue tumor of low malignant potential, which most often arises in the lower
      extremities. Lesions occurred in other anatomic locations have been rarely
      reported. Moreover, their imaging features have not been well discussed. Here we
      report a case of PHAT arising primarily in the pelvic retroperitoneum. To our
      knowledge, this is the first radiological description for retroperitoneum PHAT.
      CASE PRESENTATION: A 26-year-old female was referred to our hospital for
      evaluation of a pelvic mass incidentally noted in routine pre-pregnancy
      ultrasonography examination. Magnetic resonance imaging (MRI) and computed
      tomography (CT) scan revealed an irregular mass with clear boundary in the pelvic
      retroperitoneum. Its signal intensity or density was inhomogeneous. On MRI
      images, it mainly showed isointense and slight hypointense on T1 weighted image
      and isointense and hyperintense on T2 weighted image. On contrast-enhanced
      images, it showed marked but heterogenous enhancement. With the delay time
      increasing, the enhanced area in the lesion increased but the CT value decreased.
      Dilated vessels and hemorrhage were detected in the tumor. With patience and
      careful separation, it was completely excised with great amount of bleeding
      during operation. Pathological and immunohistochemistry analysis confirmed the
      diagnosis of PHAT of the soft parts. We found no evidence of recurrence 18 months
      after operation. CONCLUSION: We present an extremely rare case of PHAT arising
      primarily in the pelvic retroperitoneum. To our knowledge, this is the first
      radiological description for retroperitoneum PHAT. The provided information is
      useful for summarizing the characteristics of this kind of tumor. It should be
      included in the differential diagnosis of a well-defined, inhomogenously enhanced
      hypervascular soft-tissue mass in pelvic cavity.

PMID- 27044421
TI  - Incorporation of tissue-based genomic biomarkers into localized prostate cancer
      clinics.
AB  - Localized prostate cancer (PCa) is a clinically heterogeneous disease, which
      presents with variability in patient outcomes within the same risk stratification
      (low, intermediate or high) and even within the same Gleason scores. Genomic
      tools have been developed with the purpose of stratifying patients affected by
      this disease to help physicians personalize therapies and follow-up schemes. This
      review focuses on these tissue-based tools. At present, four genomic tools are
      commercially available: DecipherTM, Oncotype DX(r), Prolaris(r) and ProMark(r).
      DecipherTM is a tool based on 22 genes and evaluates the risk of adverse outcomes
      (metastasis) after radical prostatectomy (RP). Oncotype DX(r) is based on 17
      genes and focuses on the ability to predict outcomes (adverse pathology) in very
      low-low and low-intermediate PCa patients, while Prolaris(r) is built on a panel
      of 46 genes and is validated to evaluate outcomes for patients at low risk as
      well as patients who are affected by high risk PCa and post-RP. Finally,
      ProMark(r) is based on a multiplexed proteomics assay and predicts PCa
      aggressiveness in patients found with similar features to Oncotype DX(r). These
      biomarkers can be helpful for post-biopsy decision-making in low risk patients
      and post-radical prostatectomy in selected risk groups. Further studies are
      needed to investigate the clinical benefit of these new technologies, the
      financial ramifications and how they should be utilized in clinics. 

PMID- 27044422
TI  - Constructing ultrathin film with "memory" photocatalytic activity from
      monolayered tungstate nanodots.
AB  - An ultrathin film of monolayered tungstate nanodots was successfully fabricated
      via a layer-by-layer self-assembly method, which shows a "memory" photocatalytic
      activity. Photoinduced electrons are quickly stored in the ultrathin film upon
      irradiation due to the reduction of W(6+) to W(5+), and discharged to produce
      superoxides, enabling post-irradiation antibacterial activities. 

PMID- 27044423
TI  - Mesangial cells from patients with IgA nephropathy have increased susceptibility
      to galactose-deficient IgA1.
AB  - BACKGROUND: IgA nephropathy (IgAN) is the most common glomerulonephritis in the
      world, affecting close to a million people. Circulating galactose-deficient IgA
      (gd-IgA), present in patients with IgAN, form immune complex deposits in the
      glomerular mesangium causing local proliferation and matrix expansion. Intriguing
      though, individuals having gd-IgA deposits in the kidneys do not necessarily have
      signs of glomerular disease. Recurrence of IgAN only occurs in less than half of
      transplanted patients with IgAN, indicating that gd-IgA is not the only factor
      driving the disease. We hypothesize that, in addition to IgA complexes, patients
      with IgAN possess a subtype of mesangial cells highly susceptible to gd-IgA
      induced cell proliferation. METHODS: To test the hypothesis, we designed a
      technique to culture primary mesangial cells from renal biopsies obtained from
      IgAN patients and controls. The cell response to gd-IgA treatment was then
      measured both on gene and protein level and the proliferation rate of the cells
      in response to PDGF was investigated. RESULTS: When treated with gd-IgA,
      mesangial cells from patients with IgAN express and release more PDGF compared to
      controls. In addition, the mesangial cells from patients with IgAN were more
      responsive to treatment with PDGF resulting in an increased proliferation rate of
      the cells compared to control. Mesangial cells cultured from patients with IgAN
      expressed and released more IL-6 than controls and had a higher expression of
      matrix genes. Both mesangial cells derived from patients with IgAN and controls
      increased their expressed TGFbeta1 and CCL5 when treated with gd-IgA. CONCLUSION:
      We conclude that mesangial cells derived from IgAN patients have a
      mesangioproliferative phenotype with increased reactivity to IgA and that these
      cellular intrinsic properties may be important for the development of IgA
      nephropathy.

PMID- 27044424
TI  - Molecular epidemiology of hepatitis D virus circulating in Southwestern Nigeria.
AB  - BACKGROUND: Hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are
      major public health problems in sub-Saharan Africa. Whereas it is known that HBV
      infection is endemic in Nigeria, there is only little data about HDV prevalence
      available. Here, we assessed the HDV seroprevalence and determined the HDV and
      HBV genotypes distribution among HBsAg positive individuals in Southwestern
      Nigeria. METHODS: This cross-sectional study involved 188 serum samples from
      HBsAg positive outpatients recruited at four tertiary hospitals in Southwestern
      Nigeria. Anti-HDV antibodies were detected by ELISA while HDV-RNA was detected by
      RT-PCR. Sequencing followed by phylogenetic analyses and HBV genotype-specific
      PCR were used to characterize HDV and HBV genotypes, respectively. RESULTS: Out
      of 188 HBsAg positive serum samples, 17 (9 %) showed detectable HDV-RNA. Anti-HDV
      antibodies test was possible from 103 samples and were observed in 4.9 % (5/103)
      patients. There was no significant difference in HDV prevalence between four main
      cities across the country. 64.7 % of HDV-RNA positive samples were from males and
      35.3 % from females (P < 0.05). No significant associations were observed with
      regard to HDV seroprevalence and available demographic factors. Phylogenetic
      analyses demonstrated a predominance of HDV genotype 1 and HBV genotype E among
      the HDV-RNA/HBsAg positive patients. CONCLUSIONS: In conclusion, our study showed
      a high prevalence of HDV infection in HBsAg carriers and the predominance of HDV
      genotype 1 infection in Nigerian HBV endemic region. The findings contribute to a
      better understanding of the relevance of HDV/HBV co-infection and circulating
      genotypes.

PMID- 27044425
TI  - A randomized trial of the effects of the noble gases helium and argon on
      neuroprotection in a rodent cardiac arrest model.
AB  - BACKGROUND: The noble gas xenon is considered as a neuroprotective agent, but
      availability of the gas is limited. Studies on neuroprotection with the abundant
      noble gases helium and argon demonstrated mixed results, and data regarding
      neuroprotection after cardiac arrest are scant. We tested the hypothesis that
      administration of 50% helium or 50% argon for 24 h after resuscitation from
      cardiac arrest improves clinical and histological outcome in our 8 min rat
      cardiac arrest model. METHODS: Forty animals had cardiac arrest induced with
      intravenous potassium/esmolol and were randomized to post-resuscitation
      ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h. Eight
      additional animals without cardiac arrest served as reference, these animals were
      not randomized and not included into the statistical analysis. Primary outcome
      was assessment of neuronal damage in histology of the region I of hippocampus
      proper (CA1) from those animals surviving until day 5. Secondary outcome was
      evaluation of neurobehavior by daily testing of a Neurodeficit Score (NDS), the
      Tape Removal Test (TRT), a simple vertical pole test (VPT) and the Open Field
      Test (OFT). Because of the non-parametric distribution of the data, the
      histological assessments were compared with the Kruskal-Wallis test. Treatment
      effect in repeated measured assessments was estimated with a linear regression
      with clustered robust standard errors (SE), where normality is less important.
      RESULTS: Twenty-nine out of 40 rats survived until day 5 with significant initial
      deficits in neurobehavioral, but rapid improvement within all groups randomized
      to cardiac arrest. There were no statistical significant differences between
      groups neither in the histological nor in neurobehavioral assessment.
      CONCLUSIONS: The replacement of air with either helium or argon in a 50:50
      air/oxygen mixture for 24 h did not improve histological or clinical outcome in
      rats subjected to 8 min of cardiac arrest.

PMID- 27044427
TI  - Modeling Sexual Assault Risk Perception Among Heterosexual College Females: The
      Impact of Previous Victimization, Alcohol Use, and Coping Style.
AB  - This investigation utilizes structural equation modeling (SEM) to build and test
      a comprehensive model of specific and global risk perception. A sample of 325
      undergraduate females responded to measures of previous victimization,
      problematic alcohol use, and maladaptive coping. They also rated perceived risk
      in multiple hypothetical dating vignettes. The results revealed strong
      relationships between problematic alcohol use and both decreased specific and
      increased global risk perception. In addition, previous victimization and
      maladaptive coping were related to increased global risk perception and specific
      risk perception, respectively. These findings carry implications for theories of
      risk perception and point to new approaches for research.

PMID- 27044426
TI  - Serine/threonine kinases 31(STK31) may be a novel cellular target gene for the
      HPV16 oncogene E7 with potential as a DNA hypomethylation biomarker in cervical
      cancer.
AB  - BACKGROUND: Cervical cancer (CC) is a leading cause of mortality in females,
      especially in developing countries. The two viral oncoproteins E6 and E7 mediate
      the oncogenic activities of high-risk human papillomavirus (hrHPV), and hrHPV,
      especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through
      different pathways. STK31 gene of which the expression has been proven to be
      regulated by the methylation status of its promoter, is one of the novel
      cancer/testis (CT) genes and plays important roles in human cancers. Reasearches
      have indicated that viral infection is correlated to the methylation statuses of
      some genes. Herein, we detected methylation status of the STK31 gene in cervical
      tumors and explored its interaction with HPV16 or/and HPV18 (HPV16/18) infection.
      METHODS: Bisulfite genomic sequencing PCR (BGS) combined with TA clone,
      methylation-specific PCR (MSP) were used to analyze methylation statuses of the
      STK31 gene promoter/exon 1 region in HPV16/18-positive, HPV-negative CC cell
      lines; ectopically expressed HPV16 E6, -E7, and -E6/E7 CC cells; normal cervical
      tissues and cervical tumor tissues of different stages. The mRNA and protein
      expressions of STK31 were detected by RT-PCR and western blotting. RESULTS: The
      STK31 gene promoter/exon 1 was hypomethylated in the HPV16/18-positive cell lines
      HeLa, SiHa and CaSki, and the mRNA and protein expression were detected. In
      contrast, the STK31 gene exhibited hypermethylation and silenced expression in
      the HPV-negative CC cells C33A and HT-3. Compared with the primary HPV-negative
      CC cell lines, the STK31 methylation was downregulated, and STK31 expression was
      induced in the HPV16E7/E67 transfected cells. The methylation statuses and
      expressions of STK31 were verified in the cervical tumor samples at different
      stages. Additionally, chemotherapy treatment may influence STK31 expression by
      regulating its methylation status. CONCLUSIONS: STK31 may be a novel cellular
      target gene for the HPV16 oncogeneE7. The HPV16 oncogene E7 may affect STK31
      expression through a methylation-mediated mechanism. The aberrant methylation of
      the STK31 promoter/exon 1 region may be a precursor of human cervical
      carcinogenesis and a potential DNA aberrant methylation biomarker of conditions
      ranging from precancerous disease to invasive cancer.

PMID- 27044428
TI  - The Girl Is Mine: Reframing Intimate Partner Violence and Sex Work as
      Intersectional Spaces of Gender-Based Violence.
AB  - Intimate partner violence (IPV) and sex work have been primarily constructed as
      mutually exclusive phenomena within scholarly literature, though both can be
      situated under the umbrella of gender-based violence and traced to male sexual
      proprietariness. Specialized research has resulted in deeper understanding of
      nuanced categorizations of sub-phenomena within both IPV and sex work, with
      parallel constructions along a spectrum of increasing danger. However, the
      scholarly construction of these continua as parallel-and thus unrelated-disguises
      the systemic nature of each form of violence and potentially pits victims against
      each other in the struggle for legitimacy. We propose a more systemic approach to
      understanding and researching IPV and sex work and provide examples of research
      already moving in this direction.

PMID- 27044429
TI  - A robust model of natural hepatitis C infection using hepatocyte-like cells
      derived from human induced pluripotent stem cells as a long-term host.
AB  - BACKGROUND: Hepatitis C virus (HCV) could induce chronic liver diseases and
      hepatocellular carcinoma in human. The use of primary human hepatocyte as a viral
      host is restrained with the scarcity of tissue supply. A culture model restricted
      to HCV genotype 2a (JFH-1) has been established using Huh7-derived hepatocyte.
      Other genotypes including the wild-type virus could not propagate in Huh7, Huh7.5
      and Huh7.5.1 cells. METHODS: Functional hepatocyte-like cells (HLCs) were
      developed from normal human iPS cells as a host for HCV infection. Mature HLCs
      were identified for selective hepatocyte markers, CYP450s, HCV associated
      receptors and HCV essential host factors. HLCs were either transfected with JFH-1
      HCV RNA or infected with HCV particles derived from patient serum. The enhancing
      effect of alpha-tocopherol and the inhibitory effects of INF-alpha, ribavirin and
      sofosbuvir to HCV infection were studied. The HCV viral load and HCV RNA were
      assayed for the infection efficiency. RESULTS: The fully-developed HLCs expressed
      phase I, II, and III drug-metabolizing enzymes, HCV associated receptors (claudin
      1, occludin, CD81, ApoE, ApoB, LDL-R) and HCV essential host factors (miR-122 and
      SEC14L2) comparable to the primary human hepatocyte. SEC14L2, an alpha-tocopherol
      transfer protein, was expressed in HLCs, but not in Huh7 cell, had been
      implicated in effective HCVser infection. The HLCs permitted not only the
      replication of HCV RNA, but also the production of HCV particles (HCVcc) released
      to the culture media. HLCs drove higher propagation of HCVcc derived from JFH-1
      than did the classical host Huh7 cells. HLCs infected with either JFH-1 or wild
      type HCV expressed HCV core antigen, NS5A, NS5B, NS3 and HCV negative-stand RNA.
      HLCs allowed entire HCV life cycle derived from either JFH-1, HCVcc or wild-type
      HCV (genotype 1a, 1b, 3a, 3b, 6f and 6n). Further increasing the HCVser infection
      in HLCs was achieved by incubating cell with alpha-tocopherol. The supernatant
      from infected HLCs could infect both naive HLC and Huh7 cell. Treating infected
      HLC with INF-alpha and ribavirin decreased HCV RNA in both the cellular fraction
      and the culture medium. The HLCs reacted to HCVcc or wild-type HCV infection by
      upregulating TNF-alpha, IL-28B and IL-29. CONCLUSIONS: This robust cell culture
      model for serum-derived HCV using HLCs as host cells provides a remarkable system
      for investigating HCV life cycle, HCV-associated hepatocellular carcinoma
      development and the screening for new anti HCV drugs.

PMID- 27044430
TI  - Antinuclear antibody testing: discordance between commercial laboratories.
AB  - Antinuclear antibody (ANA) test results frequently affect the course of patients'
      evaluations, diagnosis, and treatment, but different laboratory centers may yield
      conflicting results. This study investigated the degree of agreement between
      laboratory results in a group of subjects who had ANA testing performed at two
      commercial laboratories. This was a chart review study, in which all ANA tests
      ordered by the authors from one commercial laboratory over a 4-year period were
      queried. Corresponding patient charts were reviewed, and if ANA testing had also
      been performed at the second commercial laboratory, subjects were entered into
      the study. The primary measurement was agreement between paired ANA results, and
      we performed sensitivity analysis using varying criteria defining agreement
      (criteria A to criteria D [strictest to most lenient definition of agreement]).
      Other data captured included relevant data obtained through the course of
      evaluation (e.g., presenting complaints, exam findings, other laboratory data)
      and final diagnoses. Of 101 paired ANA tests, there was 18 % agreement according
      to the strictest criteria and 42 % according to the most lenient. Of the seven
      subjects with ANA-associated rheumatic disease, none of the paired tests were in
      agreement according to criteria A (two agreed according to criteria D). Our
      findings demonstrate poor agreement between paired ANA tests performed at two
      commercial laboratories. The low level of agreement may have far-reaching
      clinical implications. Specifically, this finding calls into question the
      reliability of ANA testing as it is currently performed and suggests that results
      may in part depend upon the laboratory center to which patients are referred. 

PMID- 27044431
TI  - Targeting treatments for depression: what can our patients tell us?

PMID- 27044432
TI  - Global architecture of gestational diabetes research: density-equalizing mapping
      studies and gender analysis.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with substantial
      morbidity for mothers and their offspring. While clinical and basic research
      activities on this important disease grow constantly, there is no concise
      analysis of global architecture of GDM research. Hence, it was the objective of
      this study to assess the global scientific performance chronologically,
      geographically and in relation to existing research networks and gender
      distribution of publishing authors. STUDY DESIGN: On the basis of the New Quality
      and Quantity Indices in Science (NewQIS) platform, scientometric methods were
      combined with modern visualizing techniques such as density equalizing mapping,
      and the Web of Science database was used to assess GDM-related entries from 1900
      to 2012. RESULTS: Twelve thousand five hundred four GDM-related publications were
      identified and analyzed. The USA (4295 publications) and the UK (1354
      publications) dominated the field concerning research activity, overall citations
      and country-specific Hirsch-Index, which quantified the impact of a country's
      published research on the scientific community. Semi-qualitative indices such as
      country-specific citation rates ranked New Zealand and the UK at top positions.
      Annual collaborative publications increased steeply between the years 1990 and
      2012 (71 to 1157 respectively). Subject category analysis pointed to a minor
      interest of public health issues in GDM research. Gender analysis in terms of
      publication authorship revealed a clear dominance of the male gender until 2005;
      then a trend towards gender equity started and the activity of female scientists
      grew visibly in many countries. The country-specific gender analysis revealed
      large differences, i.e. female scientists dominated the scientific output in the
      USA, whereas the majority of research was published by male authors in countries
      such as Japan. CONCLUSION: This study provides the first global sketch of GDM
      research architecture. While North-American and Western-European countries were
      dominating the GDM-related scientific landscape, a disparity exists in terms of
      research output between developed and low-resource countries. Since GDM is linked
      to considerable mortality and morbidity of mothers and their offspring and
      constitutes a tremendous burden for the healthcare systems in underserved
      countries, our findings emphasize the need to address disparities by fostering
      research endeavors, public health programs and collaborative efforts in these
      nations.

PMID- 27044433
TI  - Retinal ganglion cell death in glaucoma: Exploring the role of neuroinflammation.
AB  - In clinical glaucoma, as well as in experimental models, the loss of retinal
      ganglion cells occurs by apoptosis. This final event is preceded by inflammatory
      responses involving the activation of innate and adaptive immunity, with retinal
      and optic nerve resident glial cells acting as major players. Here we review the
      current literature on the role of neuroinflammation in neurodegeneration,
      focusing on the inflammatory molecular mechanisms involved in the pathogenesis
      and progression of the optic neuropathy. 

PMID- 27044434
TI  - Synergistic antidepressant-like effects between a kappa opioid antagonist
      (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test.
AB  - Kappa opioid (KOP) receptor antagonists and delta opioid (DOP) receptor agonists
      have antidepressant-like effects in animal tests and may be useful for treatment
      resistant depression in humans. In this study, we examined whether the
      combination of a KOP receptor antagonist and a DOP receptor agonist would produce
      a better than additive effect (i.e. synergy). LY2444296 is a short-acting
      selective nonpeptide KOP receptor antagonist. ADL5859 is a selective nonpeptide
      DOP receptor agonist which does not produce seizures and EEG disturbances. Each
      compound and combinations of the two were examined in the forced swim test (FST)
      one h post injection, a screening test for antidepressant-like effect, in male
      adult C57BL/6J mice (Jackson Lab). LY2444296 [subcutaneous (s.c.) injection] at
      10 and 30mg/kg, but not 3mg/kg, significantly decreased immobility time in a dose
      dependent manner. Intraperitoneal (i.p.) injections of ADL5859 also reduced
      immobility time dose-dependently at doses of 3 and 10mg/kg, but not at 1mg/kg. An
      analysis was conducted using the method of Tallarida and Raffa (2010), which
      employed dose equivalence. The relative potency of the drugs was determined to be
      LY2444296: ADL5859=1:0.28, which was the dose ratio for combination studies. Six
      combinations of the two compounds were tested in mice at a fixed dose ratio. We
      found that LY2444296 and ADL5859 yielded significant synergistic effects for the
      antidepressant-like effect at the combined dose ranging from 3.84mg/kg to
      9.0mg/kg. ADL5859 (10mg/kg), LY2444296 (30mg/kg) and their combined dose
      (3.84mg/kg) had no effects on locomotor activities. Since the two drugs have
      distinct pharmacological profiles, such a synergism will allow use of lower doses
      of both drugs to achieve desired antidepressant effects with fewer side effects. 

PMID- 27044435
TI  - Pharmacology of the retinal pigment epithelium, the interface between retina and
      body system.
AB  - The retinal pigment epithelium (RPE) is a close, interactive partner to the
      photoreceptors as well as an interface with the endothelium of the choroid and
      thus with the body's circulatory system. To fulfill these roles, the RPE
      communicates with neighboring tissue by secretion of a large variety of factors
      and is able to react to secreted factors via a plethora of transmembrane
      receptors. Clinically relevant local pharmacological effects are caused by anti
      VEGF-A treatment in choroidal neovascularization or by carboanhydrase inhibitors
      reducing fluid accumulation in the macula. Being exposed to the bloodstream, the
      RPE reacts to systemic disease, such as diabetes or hypertension, but also to
      systemic pharmacological intervention, for example to hypotensive drugs acting on
      the renin-angiotensin-system. Sustained pharmacological treatments, in
      particular, cause side effects at the RPE with consequences for both RPE function
      and photoreceptor survival. Among these are systemic inhibition of angiotensin
      converting enzyme, insulin treatment in diabetes and anti-VEGF-A therapy. Given
      the special anatomical and functional relationships of the RPE, pharmacological
      intervention targeting either the eye or the body systemically should take
      potential alteration of RPE and subsequently photoreceptor function into account.

PMID- 27044436
TI  - The associations between psychosocial aspects and TMD-pain related aspects in
      children and adolescents.
AB  - BACKGROUND: Temporomandibular disorders (TMD) in children and adolescents is
      prevalent with pain as a common component, and has a comorbidity with
      psychosocial problems such as stress, depression, anxiety as well as somatic
      complaints. Therefore, the aim of the study was to investigate if psychosocial
      problems in children and adolescents are associated with TMD with pain (TMD-pain)
      and TMD without pain (TMD-painfree) when compared to children and adolescents
      without TMD. METHODS: This cross-sectional study consisted of 456 randomly
      selected children and adolescents, enrolled from 10 boy's- and 10 girl's- schools
      in Jeddah, between 10 and 18 years of age. On the examination day, prior to the
      clinical examination according to Research Diagnostic Criteria for TMD Axis I and
      II, the participants first answered two validated questions about TMD pain, and
      after that the Arabic version of the Youth Self Report scale. According to their
      clinical examination and diagnosis the participants were divided into three
      groups; non-TMD group, TMD-pain group, and TMD-painfree group. RESULTS: The TMD
      pain group presents a higher frequency of the internalizing problems anxiety,
      depression and somatic complaints than non-TMD group (p < 0.05). Regarding
      externalizing problems the only significant association found was for aggressive
      behavior in the TMD-pain group (p < 0.05). The TMD-pain group also shows a higher
      frequency of social problems than the non-TMD group. However, no such difference
      was found when compared to the TMD-painfree group. There was also a significant
      association with a higher frequency of thought problems in the TMD-pain group (p
      < 0.05). The children's and adolescents' physical activities were within border
      line clinical range for all three groups, whereas the social competence was
      within the normal range. There were no significant associations between any of
      the groups in this respect. CONCLUSIONS: TMD-pain in children and adolescents
      does not seem to affect the social activities. However, TMD-pain seem to have a
      strong association to emotional, behavior and somatic functioning, with higher
      frequencies of anxiety, depression, somatic problems, aggressive behavior and
      thought problems, than children and adolescents without TMD-pain. With respect to
      the biopsychosocial model the present study indicates that there are significant
      associations to psychosocial, somatic and behavioral comorbidities and TMD-pain
      in children and adolescents in the Middle East region.

PMID- 27044437
TI  - Reliability and validity of the Edinburgh Postnatal Depression Scale (EPDS) for
      detecting perinatal common mental disorders (PCMDs) among women in low-and lower
      middle-income countries: a systematic review.
AB  - BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS), originally developed
      in Britain, is one of the most widely used screening instruments for assessing
      symptoms of the Perinatal Common Mental Disorders (PCMDs) of depression and
      anxiety. However, its potential to detect PCMDs in culturally diverse low- and
      lower-middle income countries (LALMICs) is unclear. This systematic review aimed
      to appraise formally validated local language versions of the EPDS from these
      resource-constrained settings. METHODS: Following the PRISMA protocol, we
      searched MEDLINE-OVID, CINAHL-Plus and PUBMED to identify studies reporting
      translation, cultural adaptation and formal validation of the EPDS to detect
      PCMDs among women in LALMICs. The quality of the studies meeting inclusion
      criteria was assessed using standard criteria and a new process-based criteria;
      which was developed specifically for this study. RESULTS: We identified 1281
      records among which 16 met inclusion criteria; three further papers were
      identified by hand-searching reference lists. The publications reported findings
      from 12 LALMICs in 14 native languages. Most of these local language versions of
      the EPDS (LLV-EPDS) had lower precision for identifying true cases of PCMDs among
      women in the general perinatal population compared to the original English
      version. Only one study met all criteria for culturally sensitive translation,
      the others had not established the comprehensibility of the local version amongst
      representative groups of women in pre-testing. Many studies tested the LLV-EPDS
      only amongst convenience samples recruited at single health facilities.
      Diagnostic interviews for confirmation of mental disorders could have been
      influenced by the mental health professionals' lack of blinding to the initial
      screening results. Additionally, even when diagnostic-interviews were carried out
      in the local language, questions might not have been understood as most studies
      followed standard diagnostic protocol which had not been culturally adapted.
      CONCLUSIONS: Most of the LLV-EPDS from non-English speaking low- and middle
      income-countries did not meet all criteria for formal validation of a screening
      instrument. Psychometric properties of LLV-EPDS could be enhanced by adopting the
      new process-based criteria for translation, adaptation and validation.

PMID- 27044438
TI  - Associations among sedentary and active behaviours, body fat and appetite
      dysregulation: investigating the myth of physical inactivity and obesity.
AB  - BACKGROUND: There is considerable disagreement about the association between free
      living physical activity (PA) and sedentary behaviour and obesity. Moreover
      studies frequently do not include measures that could mediate between PA and
      adiposity. The present study used a validated instrument for continuous tracking
      of sedentary and active behaviours as part of habitual daily living, together
      with measures of energy expenditure, body composition and appetite dysregulation.
      This cross-sectional study tested the relationship between inactivity and
      obesity. METHODS: 71 participants (81.7% women) aged 37.4 years (+/-14) with a
      body mass index of 29.9 kg/m2 (+/-5.2) were continuously monitored for 6-7 days
      to track free-living PA (light 1.5-3 metabolic equivalents (METs), moderate 3-6
      METs and vigorous >6 METs) and sedentary behaviour (<1.5 METs) with the SenseWear
      Armband. Additional measures included body composition, waist circumference,
      cardiovascular fitness, total and resting energy expenditure, and various health
      markers. Appetite control was assessed by validated eating behaviour
      questionnaires. RESULTS: Sedentary behaviour (11.06+/-1.72 h/day) was positively
      correlated with fat mass (r=0.50, p<0.001) and waist circumference (r=-0.65,
      p<0.001). Moderate-to-vigorous PA was negatively associated with fat mass (r=
      0.72, p<0.001) and remained significantly correlated with adiposity after
      controlling for sedentary behaviour. Activity energy expenditure was positively
      associated with the level of PA and negatively associated with fat mass.
      Disinhibition and binge eating behaviours were positively associated with fat
      mass (r=0.58 and 0.47, respectively, p<0.001). CONCLUSIONS: This study
      demonstrated clear associations among objective measures of PA (and sedentary
      behaviour), energy expenditure, adiposity and appetite control. The data indicate
      strong links between physical inactivity and obesity. This relationship is likely
      to be bidirectional.

PMID- 27044439
TI  - Sports medicine in Singapore: integrating into public hospitals and secondary
      care.

PMID- 27044440
TI  - Men's perceptions and attitudes toward their wives experiencing menopause.
AB  - In this study, we explore men's perceptions, experiences, and attitudes toward
      wives experiencing natural menopause. We interviewed 20 men using the oral
      history method. Descriptive categories of experiences, such as misconceptions
      about menopause overcome through coexistence and recognition of women's
      perspectives; recognition of women's needs and efforts to provide support; coping
      with changes in marital relations and need to start a new time in couple's life;
      and existence of several needs as husbands of women experiencing menopause were
      explored. A better understanding by men about the changes experienced by
      menopausal women fosters the development of a better emotional support for their
      wives, which improves the quality of marital relations. 

PMID- 27044441
TI  - Material stiffness parameters as potential predictors of presence of left
      ventricle myocardial infarction: 3D echo-based computational modeling study.
AB  - BACKGROUND: Ventricle material properties are difficult to obtain under in vivo
      conditions and are not readily available in the current literature. It is also
      desirable to have an initial determination if a patient had an infarction based
      on echo data before more expensive examinations are recommended. A noninvasive
      echo-based modeling approach and a predictive method were introduced to determine
      left ventricle material parameters and differentiate patients with recent
      myocardial infarction (MI) from those without. METHODS: Echo data were obtained
      from 10 patients, 5 with MI (Infarct Group) and 5 without (Non-Infarcted Group).
      Echo-based patient-specific computational left ventricle (LV) models were
      constructed to quantify LV material properties. All patients were treated equally
      in the modeling process without using MI information. Systolic and diastolic
      material parameter values in the Mooney-Rivlin models were adjusted to match echo
      volume data. The equivalent Young's modulus (YM) values were obtained for each
      material stress-strain curve by linear fitting for easy comparison. Predictive
      logistic regression analysis was used to identify the best parameters for infract
      prediction. RESULTS: The LV end-systole material stiffness (ES-YMf) was the best
      single predictor among the 12 individual parameters with an area under the
      receiver operating characteristic (ROC) curve of 0.9841. LV wall thickness (WT),
      material stiffness in fiber direction at end-systole (ES-YMf) and material
      stiffness variation (?YMf) had positive correlations with LV ejection fraction
      with correlation coefficients r = 0.8125, 0.9495 and 0.9619, respectively. The
      best combination of parameters WT + ?YMf was the best over-all predictor with an
      area under the ROC curve of 0.9951. CONCLUSION: Computational modeling and
      material stiffness parameters may be used as a potential tool to suggest if a
      patient had infarction based on echo data. Large-scale clinical studies are
      needed to validate these preliminary findings.

PMID- 27044443
TI  - Reduced protein bound uraemic toxins in vegetarian kidney failure patients
      treated by haemodiafiltration.
AB  - Introduction Indoxyl sulfate (IS) and p cresyl sulfate (PCS) are protein bound
      toxins which accumulate with chronic kidney disease. Haemodiafiltration (HDF)
      increases middle molecule clearances and has been suggested to increase IS and
      PCS clearance. We therefore wished to establish whether higher convective
      clearances with HDF would reduce IS and PCS concentrations. Methods We measured
      total plasma IS and PCS in a cohort of 138 CKD5d patients treated by On-line HDF
      (Ol-HDF), by high pressure liquid chromatography. Findings Mean patient age was
      64.6 +/- 16.5 years, 60.1% male, 57.3% diabetic, median dialysis vintage 25.9
      months (12.4-62.0). The mean ICS concentration was 79.8 +/- 56.4 umol/L and PCS
      140.3 +/- 101.8 umol/L. On multivariate analysis, IS was associated with serum
      albumin (beta 4.31,P < 0.001), and negatively with residual renal function (beta
      4.1,P = 0.02) and vegetarian diet(beta-28.3, P = 0.048) and PCS negatively with
      log C reactive protein (beta-75.8, P < 0.001) and vegetarian diet (beta-109, P =
      0.001). Vegetarian patients had lower IS and PCS levels (median 41.5 (24.2-71.9)
      vs. 78.1 (49.5-107.5) and PCS (41.6 (14.2-178.3) vs. 127.3 (77.4-205.6) umol/L,
      respectively, P < 0.05. Vegetarian patients had lower preOl-HDF serum urea, and
      phosphate (13.8 +/-3.8 vs. 18.4 +/- 5.2 mmol/L, and 1.33 +/- 0.21 vs. 1.58 +/-
      0.45 mmol/L), and estimated urea nitrogen intake (1.25 +/- 0.28 vs. 1.62 +/- 0.5
      g/kg/day), respectively, all P < 0.05. Discussion Plasma IS and PCS
      concentrations were not lower with Ol-HDF compared to previous studies in
      haemodialysis patients. However those eating a vegetarian diet had reduced IS and
      PCS concentrations. Although this could be due to differences in dietary protein
      intake, a vegetarian diet may also potentially reduce IS and PCS production by
      the intestinal microbiome.

PMID- 27044444
TI  - Inconsistent Responding in a Criminal Forensic Setting: An Evaluation of the VRIN
      r and TRIN-r Scales of the MMPI-2-RF.
AB  - Criminal forensic evaluations are complicated by the risk that examinees will
      respond in an unreliable manner. Unreliable responding could occur due to lack of
      personal investment in the evaluation, severe mental illness, and low cognitive
      abilities. In this study, 31% of Minnesota Multiphasic Personality Inventory-2
      Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008/2011) profiles were
      invalid due to random or fixed-responding (T score >= 80 on the VRIN-r or TRIN-r
      scales) in a sample of pretrial criminal defendants evaluated in the context of
      treatment for competency restoration. Hierarchical regression models showed that
      symptom exaggeration variables, as measured by inconsistently reported
      psychiatric symptoms, contributed over and above education and intellectual
      functioning in their prediction of both random responding and fixed responding.
      Psychopathology variables, as measured by mood disturbance, better predicted
      fixed responding after controlling for estimates of cognitive abilities, but did
      not improve the prediction for random responding. These findings suggest that
      random responding and fixed responding are not only affected by education and
      intellectual functioning, but also by intentional exaggeration and aspects of
      psychopathology. Measures of intellectual functioning and effort and response
      style should be considered for administration in conjunction with self-report
      personality measures to rule out rival hypotheses of invalid profiles.

PMID- 27044445
TI  - Modeling and Theory: general discussion.

PMID- 27044446
TI  - Behavior-Specific Influences for Physical Activity Among African American Women.
AB  - The purpose of this study was to describe physical activity (PA) behaviors and
      physical functioning of prehypertensive and Stage I hypertensive African American
      Women (AAW) and to examine the relationships between PA behavior, physical
      functioning, personal factors, and behavior-specific influences. Pender's Health
      Promotion Model was the conceptual framework for the study. A cross-sectional
      design and convenience sample were used. The PA domain where the greatest amount
      of time was spent was in work-related activity, followed by household, leisure
      time, and transportation activity. Personal factors most strongly correlated to
      lower PA were greater body mass index and waist circumference. AAW perceived
      moderate barriers to PA and minimal family and friend social support for PA.
      Future interventions need to focus on removing barriers to and improving social
      support for PA among AAW.

PMID- 27044447
TI  - Increased Survival of Patients with Synchronous Colorectal Peritoneal Metastases
      Receiving Preoperative Chemotherapy Before Cytoreductive Surgery and Hyperthermic
      Intraperitoneal Chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      (CRS + HIPEC) can result in long-term survival for selected patients with
      colorectal peritoneal metastases (PM). Most patients are additionally treated
      with systemic chemotherapy, but timing (adjuvant vs. preoperative) varies between
      treatment centers. This study aimed to compare short- and long-term outcomes for
      patients with synchronous colorectal PM undergoing CRS + HIPEC who received
      preoperative or adjuvant chemotherapy. METHODS: This study enrolled patients with
      synchronous colorectal PM who underwent macroscopically complete or near complete
      CRS + HIPEC. Data were collected from a prospective database containing all
      patients between 2007 and 2014. Perioperative outcome and survival were compared
      between patients who underwent adjuvant chemotherapy (adjuvant strategy [AS]) and
      those who had preoperative chemotherapy followed by adjuvant systemic
      chemotherapy if possible (preoperative strategy [PS]). RESULTS: The study
      enrolled 91 patients, 25 (28 %) of whom received preoperative chemotherapy. The
      peritoneal cancer index (PCI) score was lower and the operation length shorter
      for the patients receiving preoperative chemotherapy (both p = 0.02). The
      complication rates were comparable between the two groups. The median survival
      after diagnosis was 38.6 months in the AS group, whereas median survival was not
      reached in the PS group (p < 0.01). The 3-year overall survival rates were 50 and
      89 %, respectively. After correction for other significant prognostic factors,
      preoperative chemotherapy was independently associated with improved survival (HR
      0.23; 95 % confidence interval, 0.07-0.75; p = 0.01). CONCLUSION: Treatment with
      preoperative chemotherapy was associated with improved long-term survival after
      CRS + HIPEC compared with adjuvant chemotherapy. Ideally, a randomized controlled
      trial should be performed to investigate the optimal timing of systemic
      chemotherapy for colorectal PM patients.

PMID- 27044448
TI  - The Survival Rate and Surgical Morbidity of Abdominal Radical Trachelectomy
      Versus Abdominal Radical Hysterectomy for Stage IB1 Cervical Cancer.
AB  - PURPOSE: To compare the survival rates and morbidities of abdominal radical
      trachelectomy (ART) to abdominal radical hysterectomy (ARH) for stage IB1
      cervical cancer and to evaluate the safety of ART for tumors measuring 2-4 cm.
      METHODS: We performed a retrospective study to compare the outcomes of patients
      with stage IB1 cervical cancer who underwent ART to patients treated with ARH who
      met the inclusion criteria of a fertility-sparing surgery. All of the patients
      were treated by the same surgeon at our institution in the same period. RESULTS:
      Of the 107 and 141 patients who underwent ART and ARH, respectively, 61 and 82
      patients had a tumor >=2 cm (P = NS). With a median follow-up of 30 and 49
      months, 2 patients treated with ART and 3 patients treated with ARH recurred: the
      5-year RFS rate was 96.5 and 94.8%, respectively, for tumors >=2 cm (P = NS).
      Only 3 patients died in the ARH group: the 5-year OS rate was 100% for the ART
      and 94.8% for the ARH group for tumors >=2 cm (P = NS). Incidence rates of
      intraoperative complications were similar in the two groups (1.9% for ART and
      0.7% for ARH, P = NS). However, incidence rates of postoperative complications
      were higher in the ART group (36.4% for ART and 19.1% for ARH, P < 0.05).
      CONCLUSIONS: ART appears to have equal survival rates to ARH and can be performed
      safely in stage IB1 cervical cancers >=2 cm. However, ART is associated with more
      postoperative morbidities compared with ARH.

PMID- 27044449
TI  - l-Lysine production independent of the oxidative pentose phosphate pathway by
      Corynebacterium glutamicum with the Streptococcus mutans gapN gene.
AB  - We have recently developed a Corynebacterium glutamicum strain that generates
      NADPH via the glycolytic pathway by replacing endogenous NAD-dependent
      glyceraldehyde 3-phosphate dehydrogenase (GapA) with a nonphosphorylating NADP
      dependent glyceraldehyde 3-phosphate dehydrogenase (GapN) from Streptococcus
      mutans. Strain RE2, a suppressor mutant spontaneously isolated for its improved
      growth on glucose from the engineered strain, was proven to be a high-potential
      host for l-lysine production (Takeno et al., 2010). In this study, the suppressor
      mutation was identified to be a point mutation in rho encoding the transcription
      termination factor Rho. Strain RE2 still showed retarded growth despite the
      mutation rho696. Our strategy for reconciling improved growth with a high level
      of l-lysine production was to use GapA together with GapN only in the early
      growth phase, and subsequently shift this combination-type glycolysis to one that
      depends only on GapN in the rest of the growth phase. To achieve this, we
      expressed gapA under the myo-inositol-inducible promoter of iolT1 encoding a myo
      inositol transporter in strain RE2. The resulting strain RE2A(iol) was engineered
      into an l-lysine producer by introduction of a plasmid carrying the desensitized
      lysC, followed by examination for culture conditions with myo-inositol
      supplementation. We found that as a higher concentration of myo-inositol was
      added to the seed culture, the following fermentation period became shorter while
      maintaining a high level of l-lysine production. This finally reached a
      fermentation period comparable to that of the control GapA strain, and yielded a
      1.5-fold higher production rate compared with strain RE2. The transcript level of
      gapA, as well as the GapA activity, in the early growth phase increased in
      proportion to the myo-inositol concentration and then fell to low levels in the
      subsequent growth phase, indicating that improved growth was a result of
      increased GapA activity, especially in the early growth phase. Moreover, blockade
      of the pentose phosphate pathway through a defect in glucose 6-phosphate
      dehydrogenase did not significantly affect l-lysine production in the engineered
      GapN strains, while a drastic decrease in l-lysine production was observed for
      the control GapA strain. Determination of the intracellular NADPH/NADP(+) ratios
      revealed that the ratios in the engineered strains were significantly higher than
      the ratio of the control GapA strain irrespective of the pentose phosphate
      pathway. These results demonstrate that our strain engineering strategy allows
      efficient l-lysine production independent of the oxidative pentose phosphate
      pathway.

PMID- 27044450
TI  - Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for
      Targeted Treatment.
AB  - Osteoarthritis (OA) is a progressive, degenerative disease of articulating joints
      that not only affects the elderly, but also involves younger, more active
      individuals with prolonged participation in high physical-demand activities.
      Thus, effective therapies that are easy to adopt clinically are critical in
      limiting the societal burden associated with OA. This review is focused on intra
      articular injectable regimens and provides a comprehensive look at existing in
      vivo models of OA that might be suitable for developing, testing, and finding a
      cure for OA by intra-articular injections. We first discuss the pathology,
      molecular mechanisms responsible for the initiation and progression of OA, and
      challenges associated with disease-specific targeting of OA. We proceed to
      discuss available animal models of OA and provide a detailed perspective on the
      use of mouse models in studies of experimental OA. We finally provide a closer
      look at intra-articular injectable treatments for OA, focusing on biomaterials
      based nanoparticles, and provide a comprehensive overview of the various
      nanometer-size ranges studied.

PMID- 27044451
TI  - Adolescent vulnerability to cardiovascular consequences of chronic emotional
      stress: Review and perspectives for future research.
AB  - Emotional stress has been recognized as a modifiable risk factor for
      cardiovascular diseases. Adolescence has been proposed as a developmental period
      of vulnerability to stress. This idea has been mainly supported by experimental
      research in animals demonstrating a higher impact of chronic emotional stress in
      adolescents compared with adults. Adolescent vulnerability is also based on
      evidence that stress during this developmental period affects development, so
      that enduring changes are found in adult animals that experienced stress during
      adolescence. The purpose of the present review is to discuss experimental
      research in rodent models that investigated the impact of long-term exposure to
      stressful events during adolescence on cardiovascular function. The development
      of cardiovascular function and autonomic activity in rodents is initially
      reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular
      effects of chronic stress is presented. From the reviewed literature, perspective
      for future research is proposed to better elucidate adolescent vulnerability to
      cardiovascular complications evoked by chronic emotional stress.

PMID- 27044453
TI  - Identification of two recurrent mutations of COL1A1 gene in Chinese Van der Hoeve
      syndrome patients.
AB  - CONCLUSION: The two discovered mutations in COL1A1 gene, although first reported
      in China, are recurrent ones that have also been found elsewhere in type I
      osteogenesis imperfecta patients, suggesting their role in pathogenesis of Van
      der Hoeve syndrome. OBJECTIVES: The aim of this study is to find mutational
      patterns of COL1A1 gene that may account for the putative Van der Hoeve syndrome
      in the patients carrying symptoms of osteogenesis imperfecta, blue sclera, and
      conductive deafness. METHOD: Genomic DNA was extracted from the blood of each
      patient and exons of COL1A1 gene were amplified using PCR and sequenced. RESULTS:
      Sequencing in some of the two family members revealed point mutations in exon 26
      (c.1792C > T) and exon 43 (c.3076C > T) of COL1A1 gene, respectively.

PMID- 27044454
TI  - The development and use of the E75 (HER2 369-377) peptide vaccine.
AB  - E75 (nelipepimut-S) is an immunogenic peptide derived from the HER2 protein. When
      combined with the immunoadjuvant granulocyte-macrophage colony-stimulating factor
      (GM-CSF), nelipepimut-S has been used as a vaccine that is capable of eliciting a
      robust anti-HER2 immune response. Early-phase clinical trials that enrolled women
      with node-positive or high-risk node-negative breast cancer who had been rendered
      disease free with standard of care therapy but were at risk for recurrence,
      demonstrated the vaccine to be safe with a suggestion of clinical benefit.
      Nelipepimut-S is currently being evaluated in a Phase III clinical trial. This
      article covers the preclinical and clinical development of nelipepimut-S. 

PMID- 27044452
TI  - Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease.
AB  - Over the past two decades, many studies have identified significant contributions
      of toxic beta-amyloid peptides (Abeta) to the etiology of Alzheimer's disease
      (AD), which is the most common age-dependent neurodegenerative disease. AD is
      also recognized as a disease of synaptic failure. Abeta, generated by sequential
      proteolytic cleavages of amyloid precursor protein (APP) by BACE1 and gamma
      secretase, is one of major culprits that cause this failure. In this review, we
      summarize current findings on how BACE1-cleaved APP products impact learning and
      memory through proteins localized on glutamatergic, GABAergic, and dopaminergic
      synapses. Considering the broad effects of Abeta on all three types of synapses,
      BACE1 inhibition emerges as a practical approach for ameliorating Abeta-mediated
      synaptic dysfunctions. Since BACE1 inhibitory drugs are currently in clinical
      trials, this review also discusses potential complications arising from BACE1
      inhibition. We emphasize that the benefits of BACE1 inhibitory drugs will
      outweigh the concerns.

PMID- 27044455
TI  - Venous gas emboli detected by two-dimensional echocardiography are an imperfect
      surrogate endpoint for decompression sickness.
AB  - INTRODUCTION: In studies of decompression procedures, ultrasonically detected
      venous gas emboli (VGE) are commonly used as a surrogate endpoint for
      decompression sickness (DCS). However, VGE have not been rigorously validated as
      a surrogate endpoint for DCS. METHODS: A data set for validation of VGE as a
      surrogate endpoint for DCS was retrospectively assembled comprising maximum VGE
      grades measured using two-dimensional echocardiography and DCS outcome following
      868 laboratory man-dives. Dives were conducted according to only ten different
      experimental interventions such that the ten cumulative incidences of DCS (0-22%)
      provide relatively precise point estimates of the probability of DCS, P(DCS).
      Logistic models relating the P(DCS) to VGE grade and intervention were fitted to
      these validation data. Assessment of the models was used to evaluate the Prentice
      criteria for validating a surrogate endpoint. RESULTS: The P(DCS)) increased with
      increasing VGE grade. However, the difference in the P(DCS) between interventions
      was larger than explained by differences in VGE grades. Therefore, VGE grades did
      not largely capture the intervention effect on the true endpoint (DCS) in accord
      with the Prentice definition of a surrogate endpoint. CONCLUSIONS: VGE can be
      used for comparisons of decompression procedures in samples of subjects but must
      be interpreted cautiously. A significant difference in VGE grade probably
      indicates a difference in the P(DCS). However, failure to find a significant
      difference in VGE grades does not necessarily indicate no difference in P(DCS).

PMID- 27044456
TI  - The effect of scuba diving on airflow obstruction in divers with asthma.
AB  - BACKGROUND: People with asthma are an under-represented group amongst scuba
      divers. Many may avoid or are advised against diving due to the potential risks,
      including bronchoconstriction, pulmonary barotrauma and arterial gas embolism.
      The aim of this study was to establish whether divers with asthma were more
      likely to experience reversible airways obstruction following typical scuba
      diving than divers without asthma. METHOD: All divers with a history of asthma
      attending Operation Wallacea in Honduras were identified and peak expiratory flow
      rates (PEF) were measured pre and immediately post dive. All dives were boat
      dives in tropical sea water. Scuba dives were defined as those lasting between 40
      and 55 minutes to a depth of between 10 and 18 metres. Of the 356 divers
      attending, 22 were identified as having asthma, of whom 19 were suitable for
      testing. They were classified by treatment regimen: five on no treatment, 11 on
      salbutamol only and three on regular preventative treatment. Twenty-four divers
      without a history of asthma acted as a control group. RESULTS: Open-water scuba
      diving caused a small decrease in PEF in all populations (median decrease 4.4%, P
      < 0.001). Percentage decrease in PEF was significantly more in divers with asthma
      on regular preventative medication than in the control group (mean 9.3%, median
      decrease 6% vs. mean 3.1%, median 4.3% P = 0.039). CONCLUSION: These findings
      support the view that asthmatics are more susceptible to airway changes following
      scuba diving. Differences to previous studies are likely due to environmental
      conditions, including dive depth.

PMID- 27044457
TI  - Iatrogenic cerebral gas embolism: analysis of the presentation, management and
      outcomes of patients referred to The Alfred Hospital Hyperbaric Unit.
AB  - INTRODUCTION: The aim of this study was to review patients with iatrogenic
      cerebral gas embolism (CGE) referred to The Alfred Hospital hyperbaric unit to
      determine whether hyperbaric oxygen treatment (HBOT) reduced morbidity and
      mortality. METHODS: This is a retrospective cohort study with a contemporaneous
      comparison group of patients referred between January 1998 and December 2014. The
      primary end point was good neurological outcome at the time of discharge from
      hospital or rehabilitation facility as assessed by the Glasgow Outcome Scale (GOS
      E). RESULTS: Thirty-six patients were treated with HBOT for CGE and nine patients
      were diagnosed with CGE but did not receive HBOT. Thirty-two patients developed
      CGE from an arterial source and 13 from a venous source. The mean time from
      recognition of the event to institution of HBOT was 15 hours. Four of 45 patients
      (8.9%) died. Good neurological outcomes (defined as GOS-E 7 or 8) occurred in 27
      patients and moderate disability in 13. The only independent factor that was
      associated with good neurological outcome was time to first HBOT (OR 0.94, 0.89
      0.99; P = 0.05). Hemiplegia as the first presenting sign, however, was associated
      with poor outcome (OR 0.27, 0.06-1.08; P = 0.05). The source of embolus (arterial
      versus venous), hyperbaric treatment table used and patient age did not affect
      outcome. CONCLUSION: Appropriate treatment of CGE with hyperbaric oxygen was
      found to be impeded by delays in diagnosis and subsequent transfer of patients.
      Better neurological outcome was associated with HBOT within eight hours of CGE.

PMID- 27044458
TI  - Tympanic membrane bleeding complications during hyperbaric oxygen treatment in
      patients with or without antiplatelet and anticoagulant drug treatment.
AB  - INTRODUCTION: Middle ear barotrauma (MEBt) is a frequently occurring complication
      of hyperbaric oxygen treatment (HBOT). High-grade MEBt may involve tympanic
      membrane (TM) haemorrhaging. Although many patients undergoing HBOT use
      antiplatelet or anticoagulant drugs, it is unknown whether these drugs increase
      the risk of MEBt and particularly TM bleeding complications. METHODS: This
      multicentre, prospective cohort study investigates the prevalence of MEBt and TM
      bleeding during HBOT in patients using antiplatelet/anticoagulant drugs, compared
      with control patients not on such medications. MEBt was assessed by video
      otoscopy of the TM pre and post HBOT and scored according to the modified Teed
      score. Any complications from previous HBOT sessions were retrospectively
      documented. RESULTS: Of 73 patients receiving HBOT, 34 used
      antiplatelet/anticoagulant drugs. Mild MEBt (Teed score 1 or 2) occurred in 23 of
      these 34 patients and in 31 of the 39 controls. Teed score 3 MEBt occurred in
      only two of the control-group patients and none of the patients using
      antiplatelet/anticoagulant drugs. Two patients using anticoagulant drugs reported
      epistaxis during a previous HBOT session, epistaxis was not reported by any
      control patients. CONCLUSION: Low-grade MEBt is common during HBOT, however, high
      grade barotrauma is rare with current chamber operating procedures. Patients
      using antiplatelet/anticoagulant drugs potentially may be prone to MEBt
      associated haemorrhagic complications, but we did not observe any such increase
      in this cohort. Only mild epistaxis occurred in patients using anticoagulant
      drugs.

PMID- 27044459
TI  - Consensus guidelines for the use of ultrasound for diving research.
AB  - The International Meeting on Ultrasound for Diving Research produced expert
      consensus recommendations for ultrasound detection of vascular gas bubbles and
      the analysis, interpretation and reporting of such data. Recommendations for
      standardization of techniques to allow comparison between studies included bubble
      monitoring site selection, frequency and duration of monitoring, and use of the
      Spencer, Kisman-Masurel or Eftedal-Brubakk scales. Recommendations for reporting
      of results included description of subject posture and provocation manoeuvres
      during monitoring, reporting of untransformed data and the appropriate use of
      statistics. These guidelines are available from www.dhmjournal.com. 

PMID- 27044460
TI  - The measurement of Eustachian tube function in a hyperbaric chamber using an ear
      canal microphone.
AB  - OBJECTIVE: The purpose of this study was to further the understanding of the
      opening of the Eustachian tube in relation to changes in barometric pressure.
      DESIGN: An ear canal microphone was used to measure the specific sounds related
      to tube opening and possible eardrum movements. Five subjects with normal tube
      function were examined in a hyperbaric chamber (up to 304 kPa). All active and
      passive equalization events were recorded and correlated with the subjectively
      perceived pressure regulation in the measured ear. RESULTS: The signals recorded
      were clear and reproducible. The acoustic analysis distinguished between the
      different kinds of equalization. Subjective impressions were confirmed by the
      recorded frequency of acoustic phenomena (clicks). During compression, the
      sequence of active equalization manoeuvres was in a more regular and steady
      pattern than during decompression, when the click sounds varied. CONCLUSION: The
      study established a simple technical method for analyzing the function of the
      Eustachian tube and provided new information about barometric pressure regulation
      of the middle ear.

PMID- 27044461
TI  - A modified device for continuous non-invasive blood pressure measurements in
      humans under hyperbaric and/or oxygen-enriched conditions.
AB  - BACKGROUND: It would be desirable to safely and continuously measure blood
      pressure noninvasively under hyperbaric and/or hyperoxic conditions, in order to
      explore haemodynamic responses in humans under these conditions. METHODS: A
      systematic analysis according to 'failure mode and effects analysis' principles
      of a commercially available beat-by-beat non-invasive blood pressure monitoring
      device was performed using specifications provided by the manufacturer. Possible
      failure modes related to pressure resistance and fire hazard in hyperbaric and
      oxygen-enriched environments were identified and the device modified accordingly
      to mitigate these risks. The modified device was compared to an unaltered device
      in five healthy volunteers under normobaric conditions. Measurements were then
      performed under hyperbaric conditions (243 kPa) in five healthy subjects.
      RESULTS: Modifications required included: 1) replacement of the carbon brush
      motorized pump by pressurized air connected through a balanced pressure valve; 2)
      modification of the 12V power supply connection in the multiplace hyperbaric
      chamber, and 3) replacement of gas-filled electrolytic capacitors by solid
      equivalents. There was concurrence between measurements under normobaric
      conditions, with no significant differences in blood pressure. Measurements under
      pressure were achieved without problems and matched intermittent measurement of
      brachial arterial pressure. CONCLUSION: The modified system provides safe,
      stable, continuous non-invasive blood pressure trends under both normobaric and
      hyperbaric conditions.

PMID- 27044462
TI  - The use of hyperbaric oxygen treatment for sudden sensorineural hearing loss in
      Europe.
AB  - BACKGROUND: The aim of this study was to identify the practice differences in the
      use of hyperbaric oxygen treatment (HBOT) for sudden sensorineural hearing loss
      (SSNHL) in Europe. MATERIALS AND METHODS: A questionnaire comprising nine
      questions was built using the surveymonkey.com website. The medical directors of
      hyperbaric centres in Europe were invited by e-mail to complete the survey.
      RESULTS: A total of 192 centres were invited to participate, of which 80 (41.6%)
      from 25 countries responded. Of these, 70 were using HBOT for SSNHL. The number
      of patients with SSNHL treated in these centres over a 12-month period ranged
      from 2 to 150 (mean 34, median 18). The majority of these centres (44 of 60) were
      accepting patients if they applied within 30 days of SSNHL diagnosis; 26 of these
      60 centres were also treating patients presenting with tinnitus in isolation. The
      number of treatments ranged from five to 40 (mean 19, median 20). Forty-three of
      56 centres used one session a day, whilst 13 reported using twice daily sessions
      for at least part of the HBOT course. Treatment duration varied between 60 and
      140 minutes, and treatment pressure between 151 and 253 kPa. CONCLUSION: This
      study has documented a wide range of approaches to the treatment of SSNHL with
      HBOT across Europe.

PMID- 27044463
TI  - Detection of a persistent foramen ovale using echocardiography.
AB  - Right-to-left shunts can result in decompression illness in divers and lead to a
      number of other conditions. Transthoracic echocardiography with intravenous
      injection of bubble contrast, when performed according to a well-tested protocol
      by trained personnel, enables the safe, simple, rapid and inexpensive detection
      of right-to-left shunts, the assessment of the size of the shunts and the
      differentiation of atrial shunts from pulmonary shunts. This article summarises
      the author's views on the techniques available and his preferred protocol for
      transthoracic echocardiography. 

PMID- 27044464
TI  - Hyperbaric oxygen for the treatment of the rare combination of central retinal
      vein occlusion and cilioretinal artery occlusion.
AB  - A 43-year-old male presented with sudden onset of painless, blurred vision in his
      left eye. Dilated fundoscopic examination showed signs consistent with the
      diagnosis of a combination of central retinal vein occlusion (CRVO) and
      cilioretinal artery occlusion (CLRAO). He received daily 2-h sessions of
      hyperbaric oxygen treatment (HBOT), 253 kPa for 14 days. At the end of the HBOT
      course, the patient's left visual acuity had improved from 20/200 to 20/20.
      Dilated fundoscopic examination showed that the intra-retinal haemorrhages in the
      entire retina and the retinal whitening along the course of the CLRA seen at
      presentation had completely resolved. The combination of CLRAO and CRVO comprises
      a discrete clinical entity. Even though there are many hypotheses concerning this
      condition, it is most likely the result of elevated intraluminal pressure in the
      retinal capillaries due to CRVO that exceeds the pressure in the CLRA. HBOT may
      be an effective treatment for CRVO-associated CLRAO. 

PMID- 27044465
TI  - Transcutaneous oximetry measurement: normal values for the upper limb.
AB  - Consistent with the Committee on Publication Ethics guidelines, we the above
      authors are initiating the retraction of our paper: Young DA, Blake DF, Brown LH:
      Transcutaneous oximetry measurement: normal values for the upper limb. Diving
      Hyperb Med. 2012;42(4):208-213. We wish to make the following statement: "The
      authors voluntarily retract this article after discovering a critical error
      associated with the instrumentation used in the study, namely the fitting of
      incorrect sensor membranes on the electrodes of the transcutaneous oximetry
      device used in the study. This resulted in transcutaneous oxygen tension (PtcO2)
      measurements that were consistently lower than those that would have been
      recorded with the correct electrode membranes in place. We recently confirmed
      this by comparing the two membrane types once we discovered the error. We are in
      the process of replicating our work using the correct PtcO2 specific membranes." 

PMID- 27044466
TI  - Transcutaneous oximetry: normal values for the lower limb.
AB  - Consistent with the Committee on Publication Ethics guidelines, we the above
      authors are initiating the retraction of our paper: Blake DF, Young DA, Brown LH:
      Transcutaneous oximetry: normal values for the lower limb. Diving Hyperb Med.
      2014 September;44(3):146-153. We wish to make the following statement: "The
      authors voluntarily retract this article after discovering a critical error
      associated with the instrumentation used in the study, namely the fitting of
      incorrect sensor membranes on the electrodes of the transcutaneous oximetry
      device used in the study. This resulted in transcutaneous oxygen tension (PtcO2)
      measurements that were consistently lower than those that would be recorded with
      the correct electrode membranes in place, which we recently confirmed by
      comparing the two membrane types once we discovered the error. We are in the
      process of replicating our work using the correct PtcO2 specific membranes." 

PMID- 27044467
TI  - A comparison of the tissue oxygenation achieved using different oxygen delivery
      devices and flow rates.
AB  - Consistent with the Committee on Publication Ethics guidelines, we the above
      authors are initiating a partial retraction of our paper: Blake DF, Naidoo P,
      Brown LH, Young DA, Lippmann J: A comparison of the tissue oxygenation achieved
      using different oxygen delivery devices and flow rates. Diving Hyperb Med.
      2015;45:79-83. We wish to make the following statement: "The authors voluntarily
      retract aspects of this article after discovering a critical error associated
      with the instrumentation used in the study, namely the fitting of incorrect
      sensor membranes on the electrodes of the transcutaneous oximetry device used in
      the study. This resulted in transcutaneous oxygen tension (PtcO2) measurements
      that were consistently lower than those that would be recorded with the correct
      electrode membranes in place. This measurement error was consistent across all
      arms of the study. This non-differential information error would have created a
      bias toward the null hypothesis. Therefore, whilst the absolute values for the
      data were incorrect, the direction and implications of the significant
      associations reported in this study are unchanged." 

PMID- 27044468
TI  - Hyperbaric oxygen therapy for osteoradionecrosis.

PMID- 27044469
TI  - Retraction of three papers investigating transcutaneous oxygen tensions in
      healthy volunteers.

PMID- 27044470
TI  - Tissue oxygenation using different oxygen delivery devices and flow rates.

PMID- 27044471
TI  - Reply.

PMID- 27044472
TI  - Vale Carl Edmonds.

PMID- 27044473
TI  - Intra-Operative Cap Repositioning in Small Incision Lenticule Extraction (SMILE)
      for Enhanced Visual Recovery.
AB  - PURPOSE: To study the role of intra-operative cap repositioning in acute visual
      recovery after small incision lenticule extraction (SMILE). MATERIALS AND
      METHODS: Ninety-four eyes of 47 patients underwent the SMILE procedure for
      correction of myopic refractive error. Manifest refraction and visual quality
      parameters (optical quality analysis system) were evaluated before surgery. The
      Bowman's membrane was imaged using a handheld spectral domain optical coherence
      tomography device. All patients underwent an uneventful SMILE surgery by a single
      experienced surgeon. Intra-operative cap repositioning was done in the "right"
      eye of all patients (repositioned group) and the "left" eye of each patient
      served as controls (non-repositioned group). Visual acuity and optical quality
      were assessed 1 day and 1 week after surgery. RESULTS: Bowman's membrane
      microdistortions were found in 21.3% of eyes in the repositioned group and 59.57%
      of the eyes in the non-repositioned group (p = 0.003) on the first day after
      surgery. Comparison of optical quality parameters was carried out between eyes
      where repositioning was done and control eyes (with and without
      microdistortions). On the first day after surgery, the modulation transfer
      function (MTF) and Strehl's ratio (SR) were significantly better in the
      repositioned group when compared with the controls (p = 0.002 and p = 0.003,
      respectively). Refractive error and lenticule thickness in eyes with
      microdistortions were similar (p > 0.05) between the two groups indicating other
      contributors to acute optical quality postoperatively. CONCLUSIONS: Although the
      refractive error before surgery determines the extent of microdistortions, intra
      operative cap repositioning can reduce them, thereby expediting acute visual
      recovery after SMILE.

PMID- 27044475
TI  - The Complexities of Sexual Consent Among College Students: A Conceptual and
      Empirical Review.
AB  - Headlines publicize controversies about sexual assault among college students,
      and universities face pressure to revise their sexual consent policies. What can
      the social science literature contribute to this discussion? In this article, we
      briefly discuss reasons for the recent upsurge in attention to these issues, the
      prevalence of sexual assault among college students, and aspects of college life
      that increase the risk of sexual assault and complicate sexual consent. We then
      review the conceptual challenges of defining sexual consent and the empirical
      research on how young people navigate sexual consent in their daily lives,
      focusing primarily on studies of U.S. and Canadian students. Integrating these
      conceptual issues and research findings, we discuss implications for consent
      policies, and we present five principles that could be useful for thinking about
      consent. Finally, we discuss some of the limitations of the existing research and
      suggest directions for future research.

PMID- 27044474
TI  - Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration.
AB  - Mammals have partially lost the extensive regenerative capabilities of some
      vertebrates, possibly as a result of chromatin-remodeling mechanisms that enforce
      terminal differentiation. Here, we show that deleting the SWI/SNF component
      Arid1a substantially improves mammalian regeneration. Arid1a expression is
      suppressed in regenerating tissues, and genetic deletion of Arid1a increases
      tissue repair following an array of injuries. Arid1a deficiency in the liver
      increases proliferation, reduces tissue damage and fibrosis, and improves organ
      function following surgical resection and chemical injuries. Hepatocyte-specific
      deletion is also sufficient to increase proliferation and regeneration without
      excessive overgrowth, and global Arid1a disruption potentiates soft tissue
      healing in the ear. We show that Arid1a loss reprograms chromatin to restrict
      promoter access by transcription factors such as C/ebpalpha, which enforces
      differentiation, and E2F4, which suppresses cell-cycle re-entry. Thus, epigenetic
      reprogramming mediated by deletion of a single gene improves mammalian
      regeneration and suggests strategies to promote tissue repair after injury.

PMID- 27044476
TI  - Utilization of tooth filling services by people with disabilities in Taiwan.
AB  - BACKGROUND: The oral condition of people with disabilities has considerable
      influence on their physical and mental health. However, nationwide surveys
      regarding this group have not been conducted. For this study, we used the
      National Health Insurance Research Database to explore the tooth filling
      utilization among people with disabilities. METHODS: Using the database of the
      Ministry of the Interior in 2008 which included people with disabilities
      registered, we merged with the medical claims database in 2008 of the Bureau of
      National Health Insurance to calculate the tooth filling utilization and to
      analyze relative factors. We recruited 993,487 people with disabilities as the
      research sample. RESULTS: The tooth filling utilization was 17.53 %. The multiple
      logistic regression result showed that the utilization rate of men was lower than
      that of women (OR = 0.78, 95 % CI = 0.77-0.79) and older people had lower
      utilization rates (aged over 75, OR = 0.22, 95 % CI = 0.22-0.23) compared to
      those under the age of 20. Other factors that significantly influenced the low
      tooth filling utilization included a low education level, living in less
      urbanized areas, low economic capacity, dementia, and severe disability.
      CONCLUSION: We identified the factors that influence and decrease the tooth
      filling service utilization rate: male sex, old age, low education level, being
      married, indigenous ethnicity, residing in a low urbanization area, low income,
      chronic circulatory system diseases, dementia, and severe disabilities. We
      suggest establishing proper medical care environments for high-risk groups to
      maintain their quality of life.

PMID- 27044477
TI  - Treatment of severe frostbite with iloprost in northern Canada.

PMID- 27044478
TI  - Transparency poor in academic medical research.

PMID- 27044479
TI  - Britain's "sugar tax" tackles obesity.

PMID- 27044480
TI  - Safety of fentanyl initiation according to past opioid exposure among patients
      newly prescribed fentanyl patches.
AB  - BACKGROUND: Although a convenient opioid delivery system, transdermal fentanyl
      patches have caused several deaths and resulted in safety warnings reminding
      prescribers that fentanyl patches should be prescribed only for patients who have
      adequate prior exposure to opioids. We conducted a longitudinal analysis of the
      safety of fentanyl initiation by examining past opioid exposure among patients
      newly prescribed fentanyl patches. METHODS: We identified all patients in the
      province of Manitoba who were newly prescribed fentanyl patches between Apr. 1,
      2001, and Mar. 31, 2013. We converted all prior opioid use to oral morphine
      equivalents and determined the average daily dose in the 7-30 days before initial
      fentanyl patch use. Fentanyl initiation was considered unsafe if the patient's
      pre-fentanyl opioid exposure was below the recommended level. RESULTS: We
      identified 11 063 patients who began using fentanyl patches during the study
      period. Overall, fentanyl initiation was deemed unsafe in 74.1% of cases because
      the patient's prior opioid exposure was inadequate. Women and patients 65 years
      of age and older were more likely than men and younger patients, respectively, to
      have inadequate prior opioid exposure (p < 0.001 for each comparison). The
      proportion of patients who had unsafe prescriptions for fentanyl patches
      decreased significantly over the study period, from 87.0% in 2001 to 50.0% in
      2012 (p < 0.001). INTERPRETATION: The safety of fentanyl initiation improved over
      the study period, but still half of fentanyl patch prescriptions were written for
      patients with inadequate prior opioid exposure. Review of prior opioid exposure
      may be a simple but important way to improve the safe use of fentanyl patches.

PMID- 27044481
TI  - Guru of graphic medicine.

PMID- 27044482
TI  - Consequences of unsafe prescribing of transdermal fentanyl.

PMID- 27044483
TI  - Early-Stage Investigators and Institutional Interface: Importance of Organization
      in the Mentoring Culture of Today's Universities.
AB  - Mentors have an active role in teaching mentees to scan their academic
      environments for the resources to advance their research careers, to assess the
      gaps between what's available and needed to succeed, and to develop strategies to
      fill these gaps. Yet achieving instrumentality is a necessary, but insufficient
      condition by which to accomplish the desired endpoints. Mentors and mentees must
      recognize that the organizations to which they belong are cultural in nature:
      characterized by vision, values, norms, systems, symbols, language, assumptions,
      beliefs, and habits. Understanding the collective behaviors and assumptions of
      peers and leaders in terms of the shared perceptions, thoughts, and feelings of
      organizational membership is essential to success. Institutions, in turn, must
      examine the extent to which they offer action possibilities: opportunities that
      promote the developmental trajectories of early stage investigators-in-training.
      Lack of awareness of the possible dissonance of this reality adversely affects
      many young faculty members.

PMID- 27044484
TI  - Comparative observational study of mortality amenable by health policy and care
      between rural and urban Finland: no excess segregation of mortality in the
      capital despite its increasing residential differentiation.
AB  - BACKGROUND: Large cities are often claimed to display more distinct geographical
      and socioeconomic health inequalities than other areas due to increasing
      residential differentiation. Our aim was to assess whether geographical
      inequalities in mortality within the capital (City of Helsinki) both exceeded
      that in other types of geographical areas in Finland, and whether those
      differences were dependent on socioeconomic inequalities. METHODS: We analysed
      the inequality of distribution separately for overall, ischemic heart disease and
      alcohol-related mortality, and mortality amenable (AM) to health care
      interventions in 1992-2008 in three types of geographical areas in Finland: City
      of Helsinki, other large cities, and small towns and rural areas. Mortality data
      were acquired as secondary data from the Causes of Death statistics from
      Statistics Finland. The assessment of changing geographical differences over
      time, that is geographical inequalities, was performed using Gini coefficients.
      As some of these differences might arise from socioeconomic factors, we assessed
      socioeconomic differences with concentration indices in parallel to an analysis
      of geographical differences. To conclude the analysis, we compared the changes
      over time of these inequalities between the three geographical areas. RESULTS:
      While mortality rates mainly decreased, alcohol-related mortality in the lowest
      income quintile increased. Statistically significant differences over time were
      found in all mortality groups, varying between geographical areas. Socioeconomic
      differences existed in all mortality groups and geographical areas. In the study
      period, geographical differences in mortality remained relatively stable but
      income differences increased substantially. For instance, the values of
      concentration indices for AM changed by 54 % in men (p < 0.027) and by 62 % in
      women (p < 0.016). Only slight differences existed in the time trends of Gini or
      in the concentration indices between the geographical areas. CONCLUSIONS: No
      geographical or income-related differences in the distribution of mortality
      existed between Helsinki and other urban or rural areas of Finland. This suggests
      that the effect of increasing residential differentiation in the capital may have
      been mitigated by the policies of positive discrimination and social mixing. One
      of the main reasons for the increase in health inequalities was growth of alcohol
      related mortality, especially among those with the lowest incomes.

PMID- 27044485
TI  - Giant photostriction in organic-inorganic lead halide perovskites.
AB  - Among the many materials investigated for next-generation photovoltaic cells,
      organic-inorganic lead halide perovskites have demonstrated great potential
      thanks to their high power conversion efficiency and solution processability.
      Within a short period of about 5 years, the efficiency of solar cells based on
      these materials has increased dramatically from 3.8 to over 20%. Despite the
      tremendous progress in device performance, much less is known about the
      underlying photophysics involving charge-orbital-lattice interactions and the
      role of the organic molecules in this hybrid material remains poorly understood.
      Here, we report a giant photostrictive response, that is, light-induced lattice
      change, of >1,200 p.p.m. in methylammonium lead iodide, which could be the key to
      understand its superior optical properties. The strong photon-lattice coupling
      also opens up the possibility of employing these materials in wireless opto
      mechanical devices. 

PMID- 27044486
TI  - Identifying patients at risk for severe exacerbations of asthma: development and
      external validation of a multivariable prediction model.
AB  - BACKGROUND: Preventing exacerbations of asthma is a major goal in current
      guidelines. We aimed to develop a prediction model enabling practitioners to
      identify patients at risk of severe exacerbations who could potentially benefit
      from a change in management. METHODS: We used data from a 12-month primary care
      pragmatic trial; candidate predictors were identified from GINA 2014 and selected
      with a multivariable bootstrapping procedure. Three models were constructed,
      based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO.
      Final models were corrected for overoptimism by shrinking the regression
      coefficients; predictive performance was assessed by the area under the receiver
      operating characteristic curve (AUROC) and Hosmer-Lemeshow test. Models were
      externally validated in a data set including patients with severe asthma
      (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes). RESULTS:
      80/611 (13.1%) participants experienced >=1 severe exacerbation. Five predictors
      (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous
      hospital admission for asthma and >=1 severe exacerbation in the previous year)
      were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer
      Lemeshow p value 0.35). Adding spirometry and FeNO subsequently improved
      discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78
      to 0.81), respectively). External validation yielded AUROCs of 0.72 (95% CI 0.70
      to 0.73; 71 to 0.74 and 0.71 to 0.73) for the three models, respectively;
      calibration was best for the spirometry model. CONCLUSIONS: A simple history
      based model extended with spirometry identifies patients who are prone to asthma
      exacerbations. The additional value of FeNO is modest. These models merit an
      implementation study in clinical practice to assess their utility. TRIAL
      REGISTRATION NUMBER: NTR 1756.

PMID- 27044487
TI  - VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent
      pro-angiogenic activity.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) represent a heterogeneous cell
      population that is promising for regenerative medicine. The present study was
      designed to assess whether VCAM-1 can be used as a marker of MSC subpopulation
      with superior angiogenic potential. METHODS: MSCs were isolated from placenta
      chorionic villi (CV). The VCAM-1(+/-) CV-MSCs population were separated by Flow
      Cytometry and subjected to a comparative analysis for their angiogenic properties
      including angiogenic genes expression, vasculo-angiogenic abilities on Matrigel
      in vitro and in vivo, angiogenic paracrine activities, cytokine array, and
      therapeutic angiogenesis in vascular ischemic diseases. RESULTS: Angiogenic
      genes, including HGF, ANG, IL8, IL6, VEGF-A, TGFbeta, MMP2 and bFGF, were up
      regulated in VCAM-1(+)CV-MSCs. Consistently, angiogenic cytokines especially HGF,
      IL8, angiogenin, angiopoitin-2, MUPAR, CXCL1, IL-1beta, IL-1alpha, CSF2, CSF3,
      MCP-3, CTACK, and OPG were found to be significantly increased in VCAM-1(+) CV
      MSCs. Moreover, VCAM-1(+)CV-MSCs showed remarkable vasculo-angiogenic abilities
      by angiogenesis analysis with Matrigel in vitro and in vivo and the conditioned
      medium of VCAM-1(+) CV-MSCs exerted markedly pro-proliferative and pro-migratory
      effects on endothelial cells compared to VCAM-1(-)CV-MSCs. Finally,
      transplantation of VCAM-1(+)CV-MSCs into the ischemic hind limb of BALB/c nude
      mice resulted in a significantly functional improvement in comparison with VCAM
      1(-)CV-MSCs transplantation. CONCLUSIONS: VCAM-1(+)CV-MSCs possessed a favorable
      angiogenic paracrine activity and displayed therapeutic efficacy on hindlimb
      ischemia. Our results suggested that VCAM-1(+)CV-MSCs may represent an important
      subpopulation of MSC for efficient therapeutic angiogenesis.

PMID- 27044489
TI  - Early Childhood Victimization and Physical Intimate Partner Violence During
      Pregnancy: A Developmental and Person-Oriented Approach.
AB  - Intimate partner violence (IPV) victimization during pregnancy is a major public
      health concern, yet little is known about how risk factors for IPV during
      pregnancy may depend on whether women have histories of victimization dating back
      to early childhood (ages 0-5 years). This study examined whether risk factors for
      physical IPV victimization during pregnancy (a pregnancy that was not planned and
      prenatal substance use) differed for women with versus without early childhood
      victimization. Participants were 236 ethnically diverse, low-income biological
      mothers ( M = 30.94 years; 50.0% Latina, 16.9% Caucasian, 13.1% African American,
      and 16.9% multiracial) of children aged 0 to 6 years. Mothers were classified
      into four groups based on whether they had experienced early childhood
      victimization and physical IPV victimization during pregnancy with the target
      child. Multinomial logistic regressions, controlling for demographic
      characteristics, examined whether a pregnancy not planned and prenatal substance
      use predicted group membership. Compared to mothers with early victimization
      only, mothers with both early childhood victimization and physical IPV during
      pregnancy were more than 3 times as likely to report that their pregnancy with
      the target child was not planned. In follow-up analyses, mothers with early
      victimization and physical IPV during pregnancy also reported higher lifetime
      parity than mothers with physical IPV during pregnancy but no early
      victimization. Early childhood victimization may place women on a risk pathway to
      physical IPV during pregnancy, particularly if the pregnancy is not planned.
      Prevention and policy efforts should screen women for early childhood
      victimization to understand risks for physical IPV during pregnancy.

PMID- 27044488
TI  - Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo.
AB  - BACKGROUND: Preeclampsia is frequent in Kinshasa (Democratic Republic of Congo),
      especially during the dry season. We tested whether preeclampsia was associated
      with exposure to environmental metals. METHODS: Using a case-control design, 88
      women hospitalized with preeclampsia (cases) and 88 healthy pregnant women from
      the antenatal clinic (controls) were included in the study; 67 and 109 women were
      enrolled during the rainy and dry season, respectively. The concentrations of 24
      elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS)
      in 24-h urine collections. Differences in the urinary excretion of metals were
      investigated between cases and controls, and the interaction with season was
      assessed. RESULTS: Cases and controls were well matched regarding age, parity and
      duration of pregnancy. In controls, the urinary concentrations of most elements
      were substantially higher than reference values for adults from industrially
      developed countries, e.g. for lead: geometric mean (GM) 8.0 MUg/L [25(th)-75(th)
      percentile 3.1-13.8]. The daily urinary excretions of 14 metals were
      significantly higher in women with preeclampsia than in control women, e.g. for
      lead: GM 61 MUg/day (25(th)-75(th) percentile 8-345) in women with preeclampsia
      vs 9 MUg/day (25(th)-75(th) percentile 3-21) in controls (p < 0.001). A
      significant interaction was found between season and preeclampsia for several
      elements, with higher urinary excretions in preeclamptic women than controls
      during the dry season, but not during the rainy season. CONCLUSIONS: This study
      revealed not only that women with preeclampsia excrete higher amounts of several
      toxic metals, especially lead, than control women, but also that this excretion
      exhibits seasonal variation, thus possibly explaining the high incidence and
      seasonal variation of preeclampsia in Kinshasa. Although the exact sources of
      this exposure are unknown, these findings underscore the need for preventing
      environmental exposures to lead and other toxic metals.

PMID- 27044490
TI  - Coercive Sexual Environments: Development and Validation of a Scale.
AB  - In this article, we present the results of our efforts to develop and test a
      scale to operationalize and measure a neighborhood-level indicator of coercive
      sexual environments (CSEs), a construct emerging from our earlier work on safety
      and sexual threats among young girls living in chronically disadvantaged
      neighborhoods. Data for this study come from a survey of 124 adult and 79 youth
      respondents living in public housing in Washington, D.C., and participating in
      the Housing Opportunities and Services Together Demonstration, a multisite
      project testing the feasibility and effectiveness of place-based, dual-generation
      case management models to improve outcomes for vulnerable families. Our
      psychometric analysis indicates that the CSE scales we developed for adults and
      youth have high internal consistency. Together with our analyses of construct
      validity, the present findings suggest that CSE is a unitary construct that may
      be an important factor to include in models of neighborhood processes and risk.

PMID- 27044491
TI  - Examining the Role of Substance Abuse in Elder Mistreatment: Results From
      Mistreatment Investigations.
AB  - Substance abuse has long been identified as a risk factor for elder mistreatment,
      yet research on the topic remains sparse. This study tested hypotheses whether
      perpetrator and victim substance use problems were associated with financial
      exploitation, physical abuse, emotional abuse, and neglect versus no abuse. Cross
      sectional data were collected on 948 cases with yes/no substantiation decisions
      where 357 cases had no abuse in elder mistreatment investigations. Hypotheses
      were tested using odds ratios, bivariate, and multiple linear regression analyses
      including a control for victim vulnerability. Of 948 alleged victims, 42 (4.4%)
      exhibited signs of substance use problems. Among the 323 alleged perpetrators, 87
      (26.9%) were reported to have substance use problems. Substance use problems by
      alleged perpetrators were associated ( p < .01) with financial exploitation,
      physical abuse, and emotional abuse but not neglect. Substance use problems by
      alleged victims were associated with neglect, but not the other types. Alleged
      perpetrators with substance use problems tended to commit multiple forms of
      abuse, were male and not caregivers. Except for the findings on neglect, the
      associations with elder mistreatment were stronger for alleged perpetrators with
      substance use problems, than for alleged victims. Clarification of the role of
      perpetrator risk factors such as substance abuse should improve risk
      identification and subsequent intervention.

PMID- 27044492
TI  - Searching for Social Support Moderates the Relationship Between Polyvictimization
      and Externalizing Symptoms: A Brief Report.
AB  - Externalizing disorders emerge most readily during adolescence, especially in
      traumatized population. In this context, it is necessary to determine the factors
      influencing these disorders. The aim of this study was to evaluate the role of
      polyvictimization in developing externalizing symptoms while considering the
      possible effects of active coping related to the search for social support. The
      participants were 78 adolescents (M= 14.18,SD= 1.63) cared for in child and
      adolescent protection public services in Chile. The results of multiple
      regression analysis indicated that polyvictimization was a good predictor of
      externalizing symptoms, but searching for social support acted as a moderator in
      that relationship. The results show that searching for social support acts as a
      protective factor and decreases the adverse influence of polyvictimization over
      externalizing symptoms. Prevention and intervention programs should consider
      improvements in the coping strategies of poly-victims with externalizing
      problems.

PMID- 27044493
TI  - Violence Against Children Surveys (VACS): towards a global surveillance system.
AB  - OBJECTIVE: To describe the Violence Against Children Surveys (VACS). The survey
      is a national, household survey that systematically measures the prevalence,
      nature and consequences of sexual, physical and emotional violence against
      children. DESIGN: This report provides information about the history,
      implementation, ethical protections, utility, results, limitations, and future
      directions of the VACS work. RESULTS: The study has been implemented in 11
      countries in Africa, Asia and the Caribbean, providing each of these countries
      with baseline data and momentum to address violence against children as a public
      health and human rights priority. These data are novel in each country, and VACS
      is well poised to contribute to an existing surveillance system or be used as the
      basis of a periodic surveillance system. CONCLUSIONS: Without ongoing
      surveillance to assess prevalence and the impact of policy, prevention and
      response programming, violence will likely continue to be overlooked as the
      linchpin public health crisis that it is, globally and in individual countries.

PMID- 27044494
TI  - Big data and opportunities for injury surveillance.

PMID- 27044495
TI  - Use of syndromic surveillance data to monitor poisonings and drug overdoses in
      state and local public health agencies.
AB  - BACKGROUND: The incidence of poisoning and drug overdose has risen rapidly in the
      USA over the last 16 years. To inform local intervention approaches, local health
      departments (LHDs) in North Carolina (NC) are using a statewide syndromic
      surveillance system that provides timely, local emergency department (ED) and
      Emergency Medical Services (EMS) data on medication and drug overdoses.
      OBJECTIVE: The purpose of this article is to describe the development and use of
      a variety of case definitions for poisoning and overdose implemented in NC's
      syndromic surveillance system and the impact of the system on local surveillance
      initiatives. DESIGN, SETTING, PARTICIPANTS: Thirteen new poisoning and overdose
      related case definitions were added to NC's syndromic surveillance system and
      LHDs were trained on their use for surveillance purposes. Twenty-one LHDs were
      surveyed on the utility and impact of these new case definitions.
      RESULTS/CONCLUSIONS: Ninety-one per cent of survey respondents (n = 29) agreed or
      strongly agreed that their ability to access timely ED data was vital to inform
      community-level overdose prevention work. Providing LHDs with access to local,
      timely data to identify pockets of need and engage stakeholders facilitates the
      practice of informed injury prevention and contributes to the reduction of injury
      incidence in their communities.

PMID- 27044496
TI  - The design and evaluation of a system for improved surveillance and prevention
      programmes in resource-limited settings using a hospital-based burn injury
      questionnaire.
AB  - BACKGROUND: Limited and fragmented data collection systems exist for burn injury.
      A global registry may lead to better injury estimates and identify risk factors.
      A collaborative effort involving the WHO, the Global Alliance for Clean
      Cookstoves, the CDC and the International Society for Burn Injuries was
      undertaken to simplify and standardise inpatient burn data collection. An expert
      panel of epidemiologists and burn care practitioners advised on the development
      of a new Global Burn Registry (GBR) form and online data entry system that can be
      expected to be used in resource-abundant or resource-limited settings. METHODS:
      International burn organisations, the CDC and the WHO solicited burn centre
      participation to pilot test the GBR system. The WHO and the CDC led a webinar
      tutorial for system implementation. RESULTS: During an 8-month period, 52
      hospitals in 30 countries enrolled in the pilot and were provided the GBR
      instrument, guidance and a data visualisation tool. Evaluations were received
      from 29 hospitals (56%). KEY FINDINGS: Median time to upload completed forms was
      <10 min; physicians most commonly entered data (64%), followed by nurses (25%);
      layout, clarity, accuracy and relevance were all rated high; and a vast majority
      (85%) considered the GBR 'highly valuable' for prioritising, developing and
      monitoring burn prevention programmes. CONCLUSIONS: The GBR was shown to be
      simple, flexible and acceptable to users. Enhanced regional and global
      understanding of burn epidemiology may help prioritise the selection, development
      and testing of primary prevention interventions for burns in resource-limited
      settings.

PMID- 27044497
TI  - Injury surveillance: the next generation.

PMID- 27044498
TI  - Genital invasion or perigenital spread may pose a risk of marginal misses for
      Intensity Modulated Radiotherapy (IMRT) in anal cancer.
AB  - BACKGROUND: While intensity modulated radiotherapy (IMRT) in anal cancer is
      feasible and improves high-dose conformality, the current RTOG/AGITG contouring
      atlas and planning guidelines lack specific instructions on how to proceed with
      external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends
      genital sparing on the basis of specific genital dose constraints. Recent pattern
      of-relapse studies based on conventional techniques suggest that marginal miss
      might be a potential consequence of genital sparing. Our goal is to outline the
      potential scope and increase the awareness for this clinical issue. METHODS: We
      present and discuss four patients with perigenital spread in anal cancer in both
      early and advanced stages (three at time of first diagnosis and one in form of
      relapse). Genital/perigenital spread was observed once as direct genital
      infiltration and thrice in form of perigenital lymphatic spread. RESULTS: We
      review the available data regarding the potential consequences of genital sparing
      in anal cancer. Pattern-of-relapse studies in anal cancer after conventional
      radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest
      that genital sparing may occasionally result in marginal miss. An obvious
      hypothesis suggested by our report is that perigenital lymphovascular invasion
      might be associated with manifest inguinal N+ disease. CONCLUSIONS: Local failure
      has low salvage rates in recent anal cancer treatment series. Perigenital spread
      may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal
      misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are
      warranted. Until their publication, genital sparing should be applied with
      caution, PET/CT should be used when possible and meeting genital dose constraints
      should not be prioritized over CTV coverage, especially (but not only) in stage
      T3/4 and N+ disease.

PMID- 27044499
TI  - Association between small intestinal bacterial overgrowth and deep vein
      thrombosis.
AB  - OBJECTIVE: Small intestinal bacterial overgrowth (SIBO) has been associated with
      several diseases. The association between SIBO and deep vein thrombosis (DVT) has
      not been investigated. This study was aimed to investigate the frequency and risk
      factors for the development of DVT in patients tested for SIBO. METHODS: All 321
      eligible patients were included from the Cleveland Clinic Gastrointestinal
      Motility Lab databank from January 2008 to January 2014. Patients who were
      evaluated with glucose hydrogen/methane breath test as well as Doppler
      ultrasonography for suspected DVT were included. Patients with catheter-related
      DVT were excluded. The primary outcomes were the frequency and risk factors
      (including SIBO) for DVT in this patient population. RESULTS: Of the 321-case
      cohort, 144 patients (44.9%) tested positive for SIBO, and 53 (16.5%) had
      ultrasonographic findings of DVT. SIBO evaluation before the evaluation of DVT
      occurred in 201 patients (median time from the breath test to ultrasonography: 27
      months; interquartile range [IQR]: 11.0-45.0 months), and SIBO evaluation after
      evaluation for DVT occurred in 120 patients (median time from ultrasonography to
      the breath test: 30 months; IQR: 11.8-54.3 months). In the univariate analysis,
      DVT was associated with family history of thromboembolic events (35.8% vs 16.0%,
      P=0.001), chronic kidney diseases (CKD; 26.4% vs 13.4%, P=0.019) and the presence
      of SIBO (69.8% vs 39.9%, P<0.001). In the multivariate analysis, family history
      of thromboembolic events (odds ratio [OR]: 3.39; 95% confidence interval [CI]:
      1.67-6.87; P<0.001), CKD (OR: 2.23; 95%CI: 1.04-4.74; P = 0.037), and the
      presence of SIBO (OR: 3.27; 95% CI: 1.70-6.32; P < 0.001) remained independently
      associated with DVT. CONCLUSION: SIBO was found to be associated with DVT. The
      nature of this association warrants further investigation.

PMID- 27044500
TI  - A novel method for banking stem cells from human exfoliated deciduous teeth:
      lentiviral TERT immortalization and phenotypical analysis.
AB  - BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) have recently
      attracted attention as novel multipotential stem cell sources. However, their
      application is limited due to in vitro replicative senescence. Ectopic expression
      of telomerase reverse transcriptase (TERT) is a promising strategy for overcoming
      this replicative senescence. Nevertheless, its potential application and the
      phenotype as well as tumorigenicity have never been assessed in SHED. METHODS:
      TERT expression was stably restored in SHED (TERT-SHED) isolated from healthy
      children aged 6-8 years using lentiviral transduction with a puromycin selection
      marker. The expression of TERT was detected using reverse transcription
      polymerase chain reaction, Western blot and immunofluorescence. Surface markers
      of SHED were detected by flow cytometry. Enzyme-linked immunosorbent assay was
      used to assess senescence-associated beta-galactosidase, while CCK-8 methods were
      used to examine the proliferation capacity of SHED and TERT-SHED at different
      passages. Moreover, multilineage differentiation, karyotype, colony formation in
      soft agar, and tumor formation in nude mice of SHED and TERT-SHED were also
      examined. RESULTS: Lentiviral transduction induced stable TERT expression even in
      SHED at the 40th passage. TERT-SHED showed robust proliferation capacity and low
      concentration of beta-galactosidase. Although they had some different biomarkers
      than early passage SHED, TERT-SHED at late passage showed similar mutilineage
      differentiation as TERT at early passage. Moreover, TERT-SHED at late passage
      showed normal karyotype, no soft agar colony formation, and no tumor formation in
      nude mice. CONCLUSIONS: TERT-immortalized SHED may be a promising resource for
      stem-cell therapy, although attention should be paid to the biological behavior
      of the cells.

PMID- 27044501
TI  - Brain biometals and Alzheimer's disease - boon or bane?
AB  - Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses
      have been put forward to explain the basis of disease onset and progression. A
      complicated array of molecular events has been implicated in the pathogenesis of
      AD. It is attributed to a variety of pathological conditions that share similar
      critical processes, such as oxidative stress, proteinaceous aggregations,
      mitochondrial dysfunctions and energy failure. There is increasing evidence
      suggesting that metal homeostasis is dysregulated in the pathology of AD.
      Biometals play an important role in the normal body functioning but AD may be
      mediated or triggered by disproportion of metal ions leading to changes in
      critical biological systems and initiating a cascade of events finally leading to
      neurodegeneration and cell death. The link is multifactorial, and although the
      source of the shift in oxidative homeostasis is still unclear, current evidence
      points to changes in the balance of redox transition metals, especially iron,
      copper (Cu) and other trace metals. Their levels in the brain are found to be
      elevated in AD. In other neurodegenerative disorders, Cu, zinc, aluminum and
      manganese are involved. This paper is a review of recent advances of the role of
      metals in the pathogenesis and pathophysiology of AD and related
      neurodegenerative diseases.

PMID- 27044502
TI  - Prevalence of Congenital Anomalies in a Secondary Care Hospital in South India: A
      Cross-Sectional Study.
AB  - OBJECTIVE: To study the prevalence and types of congenital anomalies that present
      at birth in a secondary-level hospital in South India and its contribution to
      perinatal mortality. MATERIALS AND METHODS: A total of 36,074 births over 10
      years, from 2003 to 2013, were studied for the prevalence of gross congenital
      malformations at birth. It was a descriptive, cross-sectional study using data
      from the birth register and available medical records. RESULTS: The incidence of
      birth defects was 12.5 per 1000 live births, with musculoskeletal disorders being
      the commonest, followed by craniovertebral anomalies. The prevalence of anomalies
      over the past 10 years has not shown any significant change (p= 0.555).
      DISCUSSION: The high prevalence of neural tube defects indicates the need for
      periconceptional folic acid supplementation and early detection of anomalies,
      which would help in timely management. Detection of musculoskeletal anomalies
      would help in counseling patients antenatally.

PMID- 27044503
TI  - Cohort Profile: The Wenchuan Earthquake Adolescent Health Cohort Study.

PMID- 27044504
TI  - Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in
      nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits
      (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to
      reduced phagocyte-derived reactive oxygen species production. Almost half of
      patients with CGD develop inflammatory bowel disease, and the involvement of the
      intestinal microbiome in relation to this predisposing immunodeficiency has not
      been explored. RESULTS: Although CGD mice do not spontaneously develop colitis,
      we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran
      sodium sulfate colitis in association with a distinct colonic transcript and
      microbiome signature. Neither restoring NOX2 reactive oxygen species production
      nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild
      type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and
      standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from
      birth significantly reduced dextran sodium sulfate colitis susceptibility in
      p47(phox-/-) mice. We found similarly decreased colitis susceptibility in
      littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium.
      CONCLUSIONS: Our findings suggest that the microbiome signature established at
      birth may play a bigger role than phagocyte-derived reactive oxygen species in
      mediating colitis susceptibility in CGD mice. These data further support bacteria
      related disease in CGD colitis.

PMID- 27044505
TI  - Electrospun PCL/Gelatin composite fibrous scaffolds: mechanical properties and
      cellular responses.
AB  - Electrospinning of hybrid polymer has gained widespread interest by taking
      advantages of the biological property of the natural polymer and the mechanical
      property of the synthetic polymer. However, the effect of the blend ratio on the
      above two properties has been less reported despite the importance to balance
      these two properties in various tissue engineering applications. To this aim, we
      investigated the electrospun PCL/Gelatin composite fibrous scaffolds with
      different blend ratios of 4:1, 2:1, 1:1, 1:2, 1:4, respectively. The morphology
      of the electrospun samples was observed by SEM and the result showed that the
      fiber diameter distribution became more uniform with the increase of the gelatin
      content. The mechanical testing results indicated that the 2:1 PCL/Gelatin sample
      had both the highest tensile strength of 3.7 MPa and the highest elongation rate
      of about 90%. Surprisingly, the 2:1 PCL/Gelatin sample also showed the best
      mesenchymal stem cell responses in terms of attachment, spreading, and
      cytoskeleton organization. Such correlation might be partly due to the fact that
      the enhanced mechanical property, an integral part of the physical
      microenvironment, likely played an important role in regulating the cellular
      functions. Overall, our results indicated that the PCL/Gelatin sample with the
      blend ratio of 2:1 was a superior candidate for scaffolds for tissue engineering
      applications.

PMID- 27044506
TI  - Erratum.

PMID- 27044507
TI  - Therapeutic hypothermia in adult patients receiving extracorporeal life support:
      early results of a randomized controlled study.
AB  - Cardiac arrest with cerebral ischaemia frequently leads to severe neurological
      impairment. Extracorporeal life support (ECLS) has emerged as a valuable adjunct
      in resuscitation of cardiac arrest. Despite ECLS, the incidence of permanent
      neurological injury remains high. We hypothesize that patients receiving ECLS for
      cardiac arrest treated with therapeutic hypothermia at 34  degrees C have lower
      neurological complication rates compared to standard ECLS therapy at
      normothermia. Early results of this randomized study suggest that therapeutic
      hypothermia is safe in adult patients receiving ECLS, with similar complication
      rates as ECLS without hypothermia. Further studies are warranted to measure the
      efficacy of this therapy. 

PMID- 27044508
TI  - Lipidomic risk score independently and cost-effectively predicts risk of future
      type 2 diabetes: results from diverse cohorts.
AB  - BACKGROUND: Detection of type 2 diabetes (T2D) is routinely based on the presence
      of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the
      potential of plasma lipidomics as a biomarker of future T2D is unknown. Our
      objective was to develop and validate a plasma lipidomic risk score (LRS) as a
      biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for
      T2D screening. METHODS: Plasma LRS, based on significantly associated lipid
      species from an array of 319 lipid species, was developed in a cohort of
      initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS).
      The LRS derived from SAFHS as well as its recalibrated version were validated in
      an independent cohort from Australia--the AusDiab cohort. The participants were
      T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n =
      771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and
      clinically improved T2D prediction was evaluated with established statistical
      parameters in both cohorts. Modeling studies were conducted to determine whether
      the use of LRS would be cost-effective for T2D screening. The main outcome
      measures included accuracy and incremental value of the LRS over routinely used
      clinical predictors of T2D risk; validation of these results in an independent
      cohort and cost-effectiveness of including LRS in screening/intervention programs
      for T2D. RESULTS: The LRS was based on plasma concentration of dihydroceramide
      18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The
      score predicted future T2D independently of prediabetes with an accuracy of 76%.
      Even in the subset of initially euglycemic individuals, the LRS improved T2D
      prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly
      and independently. When combined with risk-stratification methods currently used
      in clinical practice, the LRS significantly improved the model fit (p < 0.001),
      information content (p < 0.001), discrimination (p < 0.001) and reclassification
      (p < 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk
      stratification combined with metformin supplementation for high-risk individuals
      was the most cost-effective strategy for T2D prevention. CONCLUSIONS: Considering
      the novelty, incremental value and cost-effectiveness of LRS it should be used
      for risk-stratification of future T2D.

PMID- 27044509
TI  - Oral noribogaine shows high brain uptake and anti-withdrawal effects not
      associated with place preference in rodents.
AB  - This study investigated the effects of noribogaine, the principal metabolite of
      the drug ibogaine, on substance-related disorders. In the first experiment, mice
      chronically treated with morphine were subjected to naloxone-precipitated
      withdrawal two hours after oral administration of noribogaine. Oral noribogaine
      dose dependently decreased the global opiate withdrawal score by up to 88% of
      vehicle control with an ED50 of 13 mg/kg. In the second experiment, blood and
      brain levels of noribogaine showed a high brain penetration and a brain/blood
      ratio of 7+/-1 across all doses tested. In a third experiment, rats given oral
      noribogaine up to 100 mg/kg were tested for abuse liability using a standard
      biased conditioned place paradigm. Noribogaine-treated rats did not display place
      preference, suggesting that noribogaine is not perceived as a hedonic stimulus in
      rodents. Retrospective review of published studies assessing the efficacy of
      ibogaine on morphine withdrawal shows that the most likely cause of the
      discrepancies in the literature is the different routes of administration and
      time of testing following ibogaine administration. These results suggest that the
      metabolite noribogaine rather than the parent compound mediates the effects of
      ibogaine on blocking naloxone-precipitated withdrawal. Noribogaine may hold
      promise as a non-addicting alternative to standard opiate replacement therapies
      to transition patients to opiate abstinence.

PMID- 27044510
TI  - Long-term feeding of Atlantic salmon in seawater with low dietary long-chain n-3
      fatty acids affects tissue status of the brain, retina and erythrocytes.
AB  - In two long-term feeding trials in seawater, Atlantic salmon were fed EPA+DHA in
      graded levels, from 1.3 to 7.4 % of fatty acids (FA, 4-24 g/kg feed) combined
      with approximately 10 % 18 : 3n-3, at 6 and 12 degrees C. Dietary EPA appeared to
      be sufficient in all diet groups, as no differences were seen in polar lipid
      tissue concentrations of either the brain, retina or erythrocytes. For DHA, a
      reduction in tissue levels was observed with low dietary supply. Effects on brain
      DHA at <=1.4 % EPA+DHA of dietary FA and retina DHA at <=2.7 % EPA+DHA of dietary
      FA were only observed in fish reared at 6 degrees C, suggesting an effect of
      temperature, whereas tissue levels of n-6 FA increased as a response to increased
      dietary n-6 FA in both the brain and the retina at both temperatures. DHA levels
      in erythrocytes were affected by <=2.7 % EPA+DHA at both temperatures. Therefore,
      DHA appears to be the limiting n-3 FA in diets where EPA and DHA are present in
      the ratios found in fishmeal and fish oil. To assess the physiological
      significance of FA differences in erythrocytes, the osmotic resistance was
      tested, but it did not vary between dietary groups. In conclusion, <=2.7 %
      EPA+DHA of FA (<=9 g/kg feed) is not sufficient to maintain tissue DHA status in
      important tissues of Atlantic salmon throughout the seawater production cycle
      despite the presence of dietary 18 : 3n-3, and effects may be more severe at low
      water temperatures.

PMID- 27044511
TI  - R-spondin1 signaling pathway is required for both the ovarian and testicular
      development in a teleosts, Nile tilapia (Oreochromis niloticus).
AB  - The furin-domain-containing peptide R-spondin 1 (RSPO1) has recently emerged as
      an important regulator of ovarian development, upregulating the WNT/beta-catenin
      pathway to oppose testis formation in mammals. However, little information has
      been reported on the Rspo1 signaling pathway in teleosts. In this study, Rspo1
      was isolated from the gonads of the Nile tilapia, Oreochromis niloticus. An in
      situ hybridization analysis demonstrated that Rspo1 is expressed in the germ
      cells of the ovary and the testis. An ontogenic analysis demonstrated that Rspo1
      expression is upregulated just before meiotic initiation in both the ovary and
      testis during the early developmental stages of the tilapia. The expression
      pattern is sexually dimorphic from 20days after hatching, with higher expression
      in the ovary. The reduction of Rspo1 expression by transcription activator-like
      (TAL) effector nuclease (TALEN) caused retarded ovarian development, the ectopic
      expression of male-dominant genes, and increased serum 11-ketotestosterone.
      Intriguingly, a deficiency of Rspo1 in XY fish caused a delay in spermatogenesis,
      the inhibition of igf3 and amh expression and a reduction in serum 11
      ketotestosterone. Furthermore, incubation with FH535, an inhibitor of the
      Rspo1/Wnt pathway, decreased beta-catenin, while increased cyp11c1 and dmrt1
      expression in the in vitro cultured ovaries; decreased cyp11c1, amh and igf3
      expression in the in vitro cultured testes. Taken together, our data suggest that
      the Rspo1 signaling pathway might be involved in both ovarian and testicular
      development in the tilapia.

PMID- 27044512
TI  - Differential responses of the somatotropic and thyroid axes to environmental
      temperature changes in the green iguana.
AB  - Growth hormone (GH), together with thyroid hormones (TH), regulates growth and
      development, and has critical effects on vertebrate metabolism. In ectotherms,
      these physiological processes are strongly influenced by environmental
      temperature. In reptiles, however, little is known about the direct influences of
      this factor on the somatotropic and thyroid axes. Therefore, the aim of this
      study was to describe the effects of both acute (48h) and chronic (2weeks)
      exposure to sub-optimal temperatures (25 and 18 degrees C) upon somatotropic and
      thyroid axis function of the green iguana, in comparison to the control
      temperature (30-35 degrees C). We found a significant increase in GH release (2.0
      fold at 25 degrees C and 1.9-fold at 18 degrees C) and GH mRNA expression (up to
      3.7-fold), mainly under chronic exposure conditions. The serum concentration of
      insulin-like growth factor-I (IGF-I) was significantly greater after chronic
      exposure (18.5+/-2.3 at 25 degrees C; 15.92+/-3.4 at 18 degrees C; vs. 9.3+/
      1.21ng/ml at 35 degrees C), while hepatic IGF-I mRNA expression increased up to
      6.8-fold. Somatotropic axis may be regulated, under acute conditions, by
      thyrotropin-releasing hormone (TRH) that significantly increased its hypothalamic
      concentration (1.45 times) and mRNA expression (0.9-fold above control),
      respectively; and somatostatin (mRNA expression increased 1.0-1.2 times above
      control); and under chronic treatment, by pituitary adenylate cyclase-activating
      peptide (PACAP mRNA expression was increased from 0.4 to 0.6 times). Also, it was
      shown that, under control conditions, injection of TRH stimulated a significant
      increase in circulating GH. On the other hand, while there was a significant rise
      in the hypothalamic content of TRH and its mRNA expression, this hormone did not
      appear to influence the thyroid axis activity, which showed a severe diminution
      in all conditions of cold exposure, as indicated by the decreases in thyrotropin
      (TSH) mRNA expression (up to one-eight of the control), serum T4 (from 11.6+/
      1.09 to 5.3+/-0.58ng/ml, after 2weeks at 18 degrees C) and T3 (from 0.87+/-0.09
      to 0.05+/-0.01ng/ml, under chronic conditions at 25 degrees C), and Type-2
      deiodinase (D2) activity (from 992.5+/-224 to 213.6+/-26.4fmolI(125)T4/mgh). The
      reduction in thyroid activity correlates with the down-regulation of metabolism
      as suggested by the decrease in the serum glucose and free fatty acid levels.
      These changes apparently were independent of a possible stress response, at least
      under acute exposure to both temperatures and in chronic treatment to 25 degrees
      C, since serum corticosterone had no significant changes in these conditions,
      while at chronic 18 degrees C exposure, a slight increase (0.38 times above
      control) was found. Thus, these data suggest that the reptilian somatotropic and
      thyroid axes have differential responses to cold exposure, and that GH and TRH
      may play important roles associated to adaptation mechanisms that support
      temperature acclimation in the green iguana.

PMID- 27044513
TI  - Executive Dysfunction Correlated With 2-Year Treatment Response in Patients With
      Late-Life Undifferentiated Somatoform Disorders.
AB  - BACKGROUND: Late-life somatoform disorders (SDs) are characterized by various
      aging-associated factors. Recently, cognitive decline, including executive
      dysfunction, has been reported as an etiological factor of late-life SDs. The
      response to treatment for late-life SDs varies from one patient to another.
      Treatment strategies for late-life SDs require these etiological factors to be
      considered. We hypothesized that the treatment response in patients with late
      life SDs was associated with executive dysfunction. OBJECTIVE: The aim of the
      present study was to confirm the changes in disease severity over a 2-year follow
      up period and to determine which etiological factors are related to the treatment
      response in patients with late-life SDs. METHODS: We examined 55 patients with
      late-life SDs who were treated with pharmacotherapy and supportive psychotherapy
      at baseline. The changes in the disease severity and cognitive profiles over a 2
      year follow-up period were evaluated. Additionally, we investigated which
      etiological factors at baseline were related to treatment resistance. RESULTS: Of
      the 55 patients who were enrolled in the present study, 31 completed the 2-year
      follow-up period. Overall, the disease severity improved significantly in
      patients with late-life SDs. On the contrary, executive function decreased
      throughout the research period. Moreover, we found that executive dysfunction and
      the presence of hyperlipidemia at baseline were related to treatment resistance.
      CONCLUSIONS: These results suggest that aging-associated etiological factors be
      considered for the treatment of late-life SDs.

PMID- 27044514
TI  - Cyberchondria: Parsing Health Anxiety From Online Behavior.
AB  - BACKGROUND: Individuals with questions about their health often turn to the
      Internet for information about their symptoms, but the degree to which health
      anxiety is related to online checking, and clinical variables, remains unclear.
      The clinical profiles of highly anxious Internet checkers, and the relationship
      to checking behavior itself, have not previously been reported. OBJECTIVE: In
      this article, we test the hypothesis, derived from cognitive-behavioral models,
      that individuals with higher levels of illness anxiety would recall having
      experienced worsening anxiety after reassurance-seeking on the Internet. METHOD:
      Data from 731 volunteers who endorsed engaging in online symptom-searching were
      collected using an online questionnaire. Severity of health anxiety was assessed
      with the Whiteley Index, functional impairment with the Sheehan Disability Scale,
      and distress recall during and after searching with a modified version of the
      Clinician's Global Impairment scale. Multiple regression analyses were conducted
      to determine variables contributing to distress during and after Internet
      checking. RESULTS: Severity of illness anxiety on the Whiteley Index was the
      strongest predictor of increase in anxiety associated with, and consequent to,
      online symptom-searching. Individuals with high illness anxiety recalled feeling
      worse after online symptom-checking, whereas those with low illness anxiety
      recalled relief. Longer-duration online health-related use was associated with
      increased functional impairment, less education, and increased anxiety during and
      after checking. CONCLUSION: Because individuals with moderate-high levels of
      illness anxiety recall experiencing more anxiety during and after searching, such
      searching may be detrimental to their health. If replicated in controlled
      experimental settings, this would suggest that individuals with illness anxiety
      should be advised to avoid using the Internet for illness-related information.

PMID- 27044515
TI  - The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms.
AB  - The COP9 signalosome (CSN) is a highly conserved protein complex, recently being
      crystallized for human. In mammals and plants the COP9 complex consists of nine
      subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3
      ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of
      pathogens. Despite the interesting and essential functions, a thorough analysis
      of the CSN subunits in evolutionary comparative perspective is missing. Here we
      compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and
      show that the most conserved subunits of eukaryotes among the nine subunits are
      CSN2 and CSN5. This may indicate a strong evolutionary selection for these two
      subunits. Despite the strong conservation of the protein sequence, the genomic
      structures of the intron/exon boundaries indicate no conservation at genomic
      level. This suggests that the gene structure is exposed to a much less selection
      compared with the protein sequence. We also show the conservation of important
      active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN
      (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing
      variants for all CSN subunits. This indicates another level of complexity of the
      CSN. Notably, most COP9-subunits were identified in all multicellular and
      unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas.
      Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the
      invention of the signalosome at the root of eukaryotes. The identification of
      alternative splice variants indicates possible "mini-complexes" or COP9 complexes
      with independent subunits containing potentially novel and not yet identified
      functions. 

PMID- 27044516
TI  - Compensation of Dosage-Sensitive Genes on the Chicken Z Chromosome.
AB  - In many diploid species, sex determination is linked to a pair of sex chromosomes
      that evolved from a pair of autosomes. In these organisms, the degeneration of
      the sex-limited Y or W chromosome causes a reduction in gene dose in the
      heterogametic sex for X- or Z-linked genes. Variations in gene dose are
      detrimental for large chromosomal regions when they span dosage-sensitive genes,
      and many organisms were thought to evolve complete mechanisms of dosage
      compensation to mitigate this. However, the recent realization that a wide
      variety of organisms lack complete mechanisms of sex chromosome dosage
      compensation has presented a perplexing question: How do organisms with
      incomplete dosage compensation avoid deleterious effects of gene dose differences
      between the sexes? Here we use expression data from the chicken (Gallus gallus)
      to show that ohnologs, duplicated genes known to be dosage-sensitive, are
      preferentially dosage-compensated on the chicken Z chromosome. Our results
      indicate that even in the absence of a complete and chromosome wide dosage
      compensation mechanism, dosage-sensitive genes are effectively dosage compensated
      on the Z chromosome. 

PMID- 27044517
TI  - Three-hour analysis of non-invasive foetal sex determination: application of
      Plexor chemistry.
AB  - BACKGROUND: The knowledge of the individual genetic "status" in the prenatal era
      is particularly relevant in the case of positive family history for genetic
      diseases, in advanced maternal age and in the general screening for foetal
      abnormalities. In this context, here, we report an innovative molecular assay
      which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and
      fast detection of the foetal sex. The study involved 132 pregnant women in their
      first 3 months of pregnancy, who agreed to give a blood sample. All the collected
      samples were immediately subjected to the separation of the plasma, which was
      utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was
      analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which
      is able to simultaneously identify, quantify and discriminate the autosomal DNA
      from the sex-linked DNA. RESULTS: Overall, the Plexor-HY assay demonstrated to be
      sensitive and specific for the determination of low-template DNA, such as the
      cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the
      samples, identifying 70 males and 62 females. As the foetal sex can be provided
      in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay
      represents a very fast, safe and non-invasive prenatal method. CONCLUSIONS: The
      possibility of determining the foetal sex in the early prenatal life consents the
      application of our assay as a helpful screening test for subjects and families at
      risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may
      be of great help even for the specialist, who might promptly advise the patients
      concerning the foetal risk of inheriting sex-linked disorders and the clinical
      utility of performing an invasive prenatal diagnosis.

PMID- 27044518
TI  - Differences in Use of Glucose Rate of Change (ROC) Arrows to Adjust Insulin
      Therapy Among Individuals With Type 1 and Type 2 Diabetes Who Use Continuous
      Glucose Monitoring (CGM).
AB  - OBJECTIVE: To understand differences between individuals with type 1 diabetes
      (T1D) and type 2 diabetes (T2D) in utilization of continuous glucose monitoring
      (CGM) data to adjust insulin therapy, either continuous subcutaneous insulin
      infusion (CSII) or multiple daily insulin injections (MDI). METHODS: We surveyed
      300 individuals who regularly used real-time CGM, using 70 questions to obtain
      information about general CGM use and response to glucose rate of change (ROC)
      arrows. RESULTS: The survey was completed by 222 T1D and 78 T2D respondents
      treated with intensive insulin therapy. T1D respondents included CSII (n = 166)
      and MDI (n = 56) users. T2D respondents were more balanced: 34 (44%) versus 44
      (56%), respectively. A larger percentage of T1D then T2D respondents reported a
      constant use of CGM (85% vs 61%, P < .001). T1D and T2D respondents reported
      similar substantial increases in correction dosages in response to rapidly
      increasing glucose (>3 mg/dL/min; 2 arrows up): +140% versus +136%, P = .4534.
      However, T1D respondents reported making smaller correction dosage reductions
      than T2D respondents in response to rapidly decreasing glucose (-42% vs -80%, P <
      .001). Differences between T1D and T2D respondents were also observed in mealtime
      dosage adjustments in response to rapidly increasing glucose compared to when
      glucose is stable (flat arrow) at 110 mg/dl: +81% versus +108%, respectively (P =
      .003). Although these adjustments are statistically different, both are large.
      CONCLUSIONS: CGM users often rely on ROC information when determining insulin
      doses and tend to be more aggressive in their insulin adjustments despite
      differences in type of diabetes.

PMID- 27044519
TI  - Interferences and Limitations in Blood Glucose Self-Testing: An Overview of the
      Current Knowledge.
AB  - In general, patients with diabetes performing self-monitoring of blood glucose
      (SMBG) can strongly rely on the accuracy of measurement results. However, various
      factors such as application errors, extreme environmental conditions, extreme
      hematocrit values, or medication interferences may potentially falsify blood
      glucose readings. Incorrect blood glucose readings may lead to treatment errors,
      for example, incorrect insulin dosing. Therefore, the diabetes team as well as
      the patients should be well informed about limitations in blood glucose testing.
      The aim of this publication is to review the current knowledge on limitations and
      interferences in blood glucose testing with the perspective of their clinical
      relevance.

PMID- 27044520
TI  - Association of opioid agonist therapy with the initiation of antiretroviral
      therapy - a systematic review.
AB  - OBJECTIVES: People who inject drugs are at high risk of HIV infection but often
      face barriers in accessing medical care including access to antiretroviral
      therapy (ART). Evidence is available about the effectiveness of opioid agonist
      therapy on drug dependency and risk behaviors. However, it remains scattered
      regarding access to ART among HIV-positive people who inject drugs. We conducted
      a systematic review to examine the association of opioid agonist therapy with ART
      initiation among HIV-positive people who inject drugs. METHODS: We searched the
      literature for evidence from seven databases. We conducted a narrative synthesis
      and meta-analysis to examine the association of opioid agonist therapy with ART
      initiation. RESULTS: Five out of 2,901 identified studies met the inclusion
      criteria. Three out of five studies reported that, HIV-positive people receiving
      opioid agonist therapy initiated ART more than those not receiving opioid agonist
      therapy. In meta-analysis, opioid agonist therapy was associated with ART
      initiation among HIV positive people who inject drugs (pooled odds ratio: 1.68;
      95% confidence interval: 1.03-2.73). CONCLUSIONS: Opioid agonist therapy is
      positively associated with ART initiation among HIV-positive people who inject
      drugs. It is important to scale up opioid agonist therapy among people who inject
      drugs to improve their ART initiation.

PMID- 27044521
TI  - Tuberculosis and HIV co-infection in Vietnam.
AB  - Tuberculosis (TB) and human immunodeficiency virus (HIV) infection are leading
      causes of disease and death in Vietnam, but TB/HIV disease trends and the profile
      of co-infected patients are poorly described. METHODS: We examined national TB
      and HIV notification data to provide a geographic overview and describe relevant
      disease trends within Vietnam. We also compared the demographic and clinical
      profiles of TB patients with and without HIV infection. RESULTS: During the past
      10 years (2005-2014) cumulative HIV case numbers and deaths increased to 298,151
      and 71,332 respectively, but access to antiretroviral therapy (ART) improved and
      new infections and deaths declined. From 2011-2014 routine HIV testing of TB
      patients increased from 58.9% to 72.5% and of all TB patients diagnosed with HIV
      in 2014, 2,803 (72.4%) received ART. The number of multidrug resistant (MDR)-TB
      cases enrolled for treatment increased almost 3-fold (578 to 1,532) from 2011
      2014. The rate of HIV co-infection in MDR and non-MDR TB cases (51/1,532; 3.3% vs
      3,774/100,555; 3.8%; OR 0.77, 95% CI 0.7-1.2) was similar in 2014. CONCLUSIONS:
      The care of TB/HIV co-infected patients have shown sustained improvement in
      Vietnam. Rising numbers of MDR-TB cases is a concern, but this is not "driven" by
      HIV co-infection.

PMID- 27044522
TI  - Uptake and effectiveness of facemask against respiratory infections at mass
      gatherings: a systematic review.
AB  - OBJECTIVES: The risk of acquisition and transmission of respiratory infections is
      high among attendees of mass gatherings (MGs). Currently used interventions have
      limitations yet the role of facemask in preventing those infections at MG has not
      been systematically reviewed. We have conducted a systematic review to synthesise
      evidence about the uptake and effectiveness of facemask against respiratory
      infections in MGs. METHODS: A comprehensive literature search was conducted
      according to the preferred reporting items for systematic reviews and meta
      analyses (PRISMA) guidelines using major electronic databases such as, Medline,
      EMBASE, SCOPUS and CINAHL. RESULTS: Of 25 studies included, the pooled sample
      size was 12710 participants from 55 countries aged 11 to 89 years, 37% were
      female. The overall uptake of facemask ranged from 0.02% to 92.8% with an average
      of about 50%. Only 13 studies examined the effectiveness of facemask, and their
      pooled estimate revealed significant protectiveness against respiratory
      infections (relative risk [RR]=0.89, 95% CI: 0.84-0.94, p<0.01), but the study
      end points varied widely. CONCLUSION: A modest proportion of attendees of MGs use
      facemask, the practice is more widespread among health care workers. Facemask use
      seems to be beneficial against certain respiratory infections at MGs but its
      effectiveness against specific infection remains unproven.

PMID- 27044523
TI  - Impact of HBeAg on the maturation and function of dendritic cells.
AB  - OBJECTIVES: HBV infection typically leads to chronic hepatitis in newborns and
      some adults with weakened immune systems. The mechanisms by which virus escapes
      immunity remain undefined. Regulatory dendritic cells (DCregs) contributing to
      immune escape have been described. We wondered whether or not HBeAg as an
      immunomodulatory protein could induce DCreg which might subsequently result into
      HBV persistence. METHODS: The immunophenotyping, T-cell activation and cytokine
      production were analyzed in HBeAg-treated DCs from normal or cyclophosphamide
      (Cy)-induced immunocompromised mice. RESULTS: HBeAg tended to promote bone marrow
      derived DCs (BMDCs) from Cy-treated mice into CD11b(high)PIR-B(+) regulatory DCs
      exhibiting the lowest T-cell stimulatory capacity and interleukin (IL)-12p70
      production compared with controls. Neutralization of IL-10 significantly
      inhibited the regulatory effect of these DCs on T-cell stimulation of mature DCs.
      After lipopolysaccharides (LPS) stimulation, marked phosphorylation of Akt was
      detected in HBeAg treated DCs from immunocompromised mice. Blocking the PI3K-Akt
      pathway by LY294002 led to an enhancement of IL-12 production. PI3K signalling
      pathway appears to be involved in the decreased IL-12 secretion by HBeAg treated
      DCs. CONCLUSIONS: These findings suggest that HBeAg may program the generation of
      a new DC subset with regulatory capacity under the condition of
      immunosuppression, which may presumably contribute to the persistent HBV
      infection.

PMID- 27044524
TI  - Do intensive services obviate the need for CTOs?
AB  - OBJECTIVE: Opponents of community treatment orders (CTOs) argue that they would
      be unnecessary if sufficient community services such as assertive community
      treatment (ACT) teams were available. This study was designed to determine the
      frequency of CTO use for patients on ACT teams; reasons why patients receiving
      ACT services are placed on CTOs; and views of stakeholders on use of CTOs on ACT
      teams. METHODS: We identified all patients on a CTO while being served by ACT
      teams in London, Ontario, between 2000 and 2013. Data were collected using chart
      review, questionnaires completed by psychiatrists and focus groups for patients,
      their relatives and non-psychiatrist clinicians. RESULTS: During the study
      period, 190 patients were on a CTO while receiving ACT services. In December
      2013, 17% of London's ACT team patients had an active CTO. ACT alone had been
      tried for 57% of patients before a CTO was introduced. Psychiatrists cited
      refusal of treatment and unavailability for follow-up as the primary reasons why
      ACT alone was ineffective. Patients were ambivalent about CTOs: describing them
      as coercive while simultaneously noting benefits. Relatives and non-psychiatrist
      clinicians were more clearly positive about the use of CTOs. CONCLUSIONS: The
      availability of intensive services does not ensure that patients will engage with
      those services. CLINICAL IMPLICATIONS: Community legislation requiring some
      patients to adhere to treatment is needed in addition to intensive clinical
      services. LIMITATIONS: This study conducted in a single location may not
      generalize to other regions. Many patients were not approached to participate in
      the focus groups which call into question the representativeness of patient
      opinions.

PMID- 27044525
TI  - An examination of stakeholder attitudes and understanding of therapeutic
      jurisprudence in a mental health court.
AB  - Mental health courts represent a key component of contemporary responses to
      mental illness and disability in the criminal justice system, and yet there is
      uncertainty about how these courts should balance their punishment and treatment
      roles. This paper reports an analysis of interviews with court professionals
      which considers their understanding of the rationale underpinning an Australian
      mental health court, its effectiveness in achieving its criminal justice and
      clinical goals, and of broader notions of therapeutic jurisprudence. This reveals
      considerable support for diversionary mental health court programs of this type
      and professional confidence that this type of program is effective. However, the
      analysis also highlights conflict in the practice frameworks of the different
      professional groups who regularly contribute to the operations of the court.
      Suggestions to enhance service delivery are offered.

PMID- 27044526
TI  - The use of a brief mental health screener to enhance the ability of police
      officers to identify persons with serious mental disorders.
AB  - Police agencies in Canada and elsewhere have received much criticism over how
      they respond to persons with serious mental disorders. The adequacy of training
      provided to police officers on mental health issues and in particular on
      recognizing indicators of serious mental disorders has been a major concern. This
      paper describes the process that led to the development of a new brief mental
      health screener (interRAI Brief Mental Health Screener, BMHS) designed to assist
      police officers to better identify persons with serious mental disorders. The
      interRAI BMHS was developed in collaboration with interRAI, an international, not
      for-profit consortium of researchers. The government of Ontario had previously
      partnered with interRAI to develop and implement the Resident Assessment
      Instrument for Mental Health (RAI-MH), the assessment system mandated for use on
      all persons admitted into inpatient psychiatric care in the province. Core items
      on the interRAI BMHS were obtained through analysis (N=41,019) of RAI-MH data
      together with input from representatives from health care, police services, and
      patient groups. Two police services in southwestern Ontario completed forms
      (N=235) on persons thought to have a mental disorder. Patient records were later
      accessed to determine patient disposition. The use of summary and inferential
      statistics revealed that the variables significantly associated with being taken
      to hospital by police included performing a self-injurious act in the past
      30days, and others being concerned over the person's risk for self-injury.
      Variables significantly associated with being admitted included abnormal thought
      process, delusions, and hallucinations. The results of the study indicate that
      the 14-variable algorithm used to construct the interRAI BMHS is a good predictor
      of who was most likely to be taken to hospital by police officers and who was
      most likely to be admitted. The instrument is an effective means of capturing and
      standardizing police officer observations enabling them to provide more and
      better quality information to emergency department (ED) staff. Teaching police
      officers to use the form constitutes enhanced training on major indicators of
      serious mental disorders. Further, given that items on the interRAI BMHS are
      written in the language of the health system, language acts as common currency
      between police officers and ED staff laying the foundation for a more
      collaborative approach between the systems.

PMID- 27044527
TI  - Time and temperature dependent multiple hierarchical NiCo2O4 for high-performance
      supercapacitors.
AB  - A multiple hierarchical NiCo2O4 (denoted as P-100), which was constructed of
      nanosheets covered with nanowires, was obtained by a facial hydrothermal method
      in combination with annealing treatment at 300  degrees C. The hydrothermal
      temperature and reaction time play key roles in the formation of the unique
      hierarchical NiCo2O4 based on the morphology evolution. As a supercapacitor
      electrode material, the obtained P-100 displays a high specific capacitance of
      1393 F g(-1) at 0.5 A g(-1). Furthermore, the assembled P-100//AC asymmetric
      supercapacitor demonstrates a high energy density (21.4 Wh kg(-1)) at a power
      density of 350 W kg(-1) and remarkable cycling stability. The good
      electrochemical performances of the P-100 are mainly due to its three dimensional
      hierarchical porous nanostructure and high specific surface area as well as the
      synergetic effect of the nanosheets and nanowires in NiCo2O4. The experimental
      results demonstrated that the multiple hierarchical NiCo2O4 is a promising
      electrode material for high-performance supercapacitors.

PMID- 27044528
TI  - Presence of three dengue serotypes in Ouagadougou (Burkina Faso): research and
      public health implications.
AB  - BACKGROUND: The significant malaria burden in Africa has often eclipsed other
      febrile illnesses. Burkina Faso's first dengue epidemic occurred in 1925 and the
      most recent in 2013. Yet there is still very little known about dengue
      prevalence, its vector proliferation, and its poverty and equity impacts.
      METHODS: An exploratory cross-sectional survey was performed from December 2013
      to January 2014. Six primary healthcare centers in Ouagadougou were selected
      based on previously reported presence of Flavivirus. All patients consulting with
      fever or having had fever within the previous week and with a negative rapid
      diagnostic test (RDT) for malaria were invited to participate. Sociodemographic
      data, healthcare use and expenses, mobility, health-related status, and vector
      control practices were captured using a questionnaire. Blood samples of every
      eligible subject were obtained through finger pricks during the survey for dengue
      RDT using SD BIOLINE Dengue Duo (NS1Ag and IgG/IgM)(r) and to obtain blood spots
      for reverse transcription polymerase chain reaction (RT-PCR) analysis. In a
      sample of randomly selected yards and those of patients, potential Aedes breeding
      sites were found and described. Larvae were collected and brought to the
      laboratory to monitor the emergence of adults and identify the species. RESULTS:
      Of the 379 subjects, 8.7 % (33/379) had positive RDTs for dengue. Following the
      2009 WHO classification, 38.3 % (145/379) had presumptive, probable, or confirmed
      dengue, based on either clinical symptoms or laboratory testing. Of 60 samples
      tested by RT-PCR (33 from the positive tests and 27 from the subsample of
      negatives), 15 were positive. The serotypes observed were DENV2, DENV3, and
      DENV4. Odds of dengue infection in 15-to-20-year-olds and persons over 50 years
      were 4.0 (CI 95 %: 1.0-15.6) and 7.7 (CI 95 %: 1.6-37.1) times higher,
      respectively, than in children under five. Average total spending for a dengue
      episode was 13 771 FCFA [1 300-67 300 FCFA] (1$US = 478 FCFA). On average, 2.6
      breeding sites were found per yard. Potential Aedes breeding sites were found
      near 71.4 % (21/28) of patients, but no adult Aedes were found. The most
      frequently identified potential breeding sites were water storage containers
      (45.2 %). Most specimens collected in yards were Culex (97.9 %). CONCLUSIONS: The
      scientific community, public health authorities, and health workers should
      consider dengue as a possible cause of febrile illness in Burkina Faso.

PMID- 27044529
TI  - Crim1-, a regulator of developmental organogenesis.
AB  - The regulation of growth factor localization, availability and activity is
      critical during embryogenesis to ensure appropriate organogenesis. This process
      is regulated through the coordinated expression of growth factors and their
      cognate receptors, as well as via proteins that can bind, sequester or localize
      growth factors to distinct locations. One such protein is the transmembrane
      protein Crim1. This protein has been shown to be expressed broadly within the
      developing embryo, and to regulate organogenesis within the eye, kidney and
      placenta. Mechanistically, Crim1 has been revealed to mediate organogenesis via
      its interaction with growth factors including TGFbetas, BMPs, VEGFs and PDFGs.
      More recently, Crim1 has been shown to influence cardiac development, providing
      further insights into the function of this protein. This review will provide an
      overview of the role of Crim1 in organogenesis, largely focusing on how this
      protein regulates growth factor signaling in the nascent heart. Moreover, we will
      address the challenges ahead relating to further elucidating how Crim1 functions
      during development. 

PMID- 27044530
TI  - The surgical plane for lingual tonsillectomy: an anatomic study.
AB  - BACKGROUND: The presence of a plane between the lingual tonsils and the
      underlying soft tissue has not been confirmed. The objective of this study is to
      ascertain the presence and the characteristics about this plane for surgical use.
      METHODS: Five cadaver heads were obtained for dissection of the lingual tonsils.
      Six permanent sections of previous tongue base biopsies were reviewed. Robot
      assisted lingual tonsillectomy was performed using the dissection technique from
      the cadaver dissection. RESULTS: In each of the 5 cadavers, an avascular plane
      was revealed deep to the lingual tonsils. Microscopic review of the tongue base
      biopsies revealed a clear demarcation between the lingual tonsils and the
      underlying minor salivary glands and muscle tissue. This area was relatively
      avascular. Using the technique described above, a lingual tonsillectomy using
      TORS was performed with similar findings from the cadaver dissections.
      CONCLUSIONS: A surgical plane for lingual tonsillectomy exists and may prove to
      have a role with lingual tonsillectomy with TORS.

PMID- 27044531
TI  - Antibody-mediated rejection of the lung: A consensus report of the International
      Society for Heart and Lung Transplantation.
AB  - Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction
      in lung transplant recipients. Unlike AMR in other solid-organ transplant
      recipients, there are no standardized diagnostic criteria or an agreed-upon
      definition. Hence, a working group was created by the International Society for
      Heart and Lung Transplantation with the aim of determining criteria for pulmonary
      AMR and establishing a definition. Diagnostic criteria and a working consensus
      definition were established. Key diagnostic criteria include the presence of
      antibodies directed toward donor human leukocyte antigens and characteristic lung
      histology with or without evidence of complement 4d within the graft. Exclusion
      of other causes of allograft dysfunction increases confidence in the diagnosis
      but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which
      can be asymptomatic) or sub-clinical (normal allograft function). This consensus
      definition will have clinical, therapeutic and research implications. 

PMID- 27044532
TI  - Clinical trial design and rationale of the Multicenter Study of MagLev Technology
      in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3
      (MOMENTUM 3) investigational device exemption clinical study protocol.
AB  - The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc.,
      formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into
      clinical trials for durable circulatory support in patients with medically
      refractory advanced-stage heart failure. This centrifugal, fully magnetically
      levitated, continuous-flow pump is engineered with the intent to enhance
      hemocompatibility and reduce shear stress on blood elements, while also
      possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and
      destination therapy (DT) are established dichotomous indications for durable left
      ventricular assist device (LVAD) support, clinical practice has challenged the
      appropriateness of these designations. The introduction of novel LVAD technology
      allows for the development of clinical trial designs to keep pace with current
      practices. The prospective, randomized Multicenter Study of MagLev Technology in
      Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3
      (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the
      HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also
      St. Jude Medical, Inc.). The innovative trial design includes patients enrolled
      under a single inclusion and exclusion criteria , regardless of the intended use
      of the device, with outcomes ascertained in the short term (ST, at 6 months) and
      long term (LT, at 2 years). This adaptive trial design includes a pre-specified
      safety phase (n = 30) analysis. The ST cohort includes the first 294 patients and
      the LT cohort includes the first 366 patients for evaluation of the composite
      primary end-point of survival to transplant, recovery or LVAD support free of
      debilitating stroke (modified Rankin score >3), or re-operation to replace the
      pump. As part of the adaptive design, an analysis by an independent statistician
      will determine whether sample size adjustment is required at pre-specified times
      during the study. A further 662 patients will be enrolled to reach a total of
      1,028 patients for evaluation of the secondary end-point of pump replacement at 2
      years. 

PMID- 27044533
TI  - MicroRNA-144 is unlikely to play a role in bronchiolitis obliterans syndrome.

PMID- 27044534
TI  - "Bioengineered lungs" Best science paper in JHLT 2014-2015.

PMID- 27044535
TI  - Human Leptospirosis in Malaysia: Reviewing the Challenges After 8 Decades (1925
      2012).
AB  - The history and epidemiology of human leptospirosis in Malaysia from 1925 to 2012
      are described. Previous studies have demonstrated that leptospirosis is an
      endemic disease in Malaysia occurring in both urban and rural locations. The
      number of cases has risen dramatically since the Ministry of Health Malaysia
      highlighted leptospirosis as a notifiable disease in 2010, with reported cases
      increasing from 248 cases in 2004 to 3604 in 2012. The incidence of infection
      among the population suggests that occupation, sex, age, ethnic background, water
      recreational activities, and sporting events are risk factors. A robust
      surveillance system is now in place to monitor temporal and spatial changes in
      the incidence and prevalence of infection and to identify risk areas and disease
      behavior. Despite extensive studies over the past decade, there is a still a need
      to describe local serovars in host carriers and the human population, with the
      view to develop an effective vaccine against leptospirosis.

PMID- 27044536
TI  - Social Capital and Quality of Life Among People Living With HIV/AIDS in Southeast
      China.
AB  - A cross-sectional study was conducted with 261 people living with HIV (PLWH) in
      Southeast China. A social capital questionnaire was used to measure social
      capital dimensions (trust, social connection, and social participation). A
      Chinese version of the Medical Outcomes Study HIV Health Survey (MOS-HIV) was
      used to assess Quality of Life (QoL); Physical Health Summary Scores (PHS) and
      Mental Health Summary Scores (MHS) were calculated. Multiple regression assessed
      whether social capital and its dimensions were associated with PHS and MHS. After
      controlling for sociodemographics and HIV-related factors, lower PHS scores were
      found among participants with low overall social capital (P < .01) and low trust
      (P < .001). Lower MHS scores were found among participants with low overall
      social capital (P < .001), low trust (P < .001) and low social connection (P <
      .01). Our findings identify potential intervention targets to improve QoL among
      PLWH in Southeast China, including the promotion of social capital.

PMID- 27044537
TI  - Chorea as a clinical feature of the basophilic inclusion body disease subtype of
      fused-in-sarcoma-associated frontotemporal lobar degeneration.
AB  - Choreoathetoid involuntary movements are rarely reported in patients with
      frontotemporal lobar degeneration (FTLD), suggesting their exclusion as a
      supportive feature in clinical diagnostic criteria for FTLD. Here, we identified
      three cases of the behavioral variant of frontotemporal dementia (bvFTD) that
      display chorea with fused in sarcoma (FUS)-positive inclusions (FTLD-FUS) and the
      basophilic inclusion body disease (BIBD) subtype. We determined the behavioral
      and cognitive features in this group that were distinct from other FTLD-FUS
      cases. We also reviewed the clinical records of 72 FTLD cases, and clarified
      additional clinical features that are predictive of the BIBD pathology. Symptom
      onset in the three patients with chorea was at 44.0 years of age (+/-12.0 years),
      and occurred in the absence of a family history of dementia. The cases were
      consistent with a clinical form of FTD known as bvFTD, as well as reduced
      neurological muscle tone in addition to chorea. The three patients showed no or
      mild parkinsonism, which by contrast, increased substantially in the other FTLD
      cases until a later stage of disease. The three patients exhibited severe caudate
      atrophy, which has previously been reported as a histological feature
      distinguishing FTLD-FUS from FTLD-tau or FTLD-TAR DNA-binding protein 43. Thus,
      our findings suggest that the clinical feature of choreoathetosis in bvFTD might
      be associated with FTLD-FUS, and in particular, with the BIBD subtype. 

PMID- 27044538
TI  - Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non
      thermal diode laser.
AB  - BACKGROUND: The use of liposomes as drug delivery systems is the most promising
      technique for targeting drug especially for anticancer therapy. METHODS: In this
      study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE
      encapsulated doxorubicin. The effect of lyophilization on liposomal stability and
      hence expiration date were studied. Moreover, the effect of diode laser on the
      drug released from liposomesin vitro and in vivo in mice carrying implanted solid
      tumor were also studied. RESULTS: The results indicated that lyophilization of
      the prepared liposomes encapsulating doxorubicin led to marked stability when
      stored at 5  degrees C and it is possible to use the re-hydrated lyophilized
      liposomes within 12 days post reconstitution. Moreover, the use of low energy
      diode laser for targeting anticancer drug to the tumor cells is a promising
      method in cancer therapy. CONCLUSION: We can conclude that lyophilization of the
      liposomes encapsulating doxorubicin lead to marked stability for the liposomes
      when stored at 5  degrees C. Moreover, the use of low energy diode laser for
      targeting anticancer drug to the tumor cells through the use of photosensitive
      sterically stabilized liposomes loaded with doxorubicin is a promising method. It
      proved to be applicable and successful for treatment of Ehrlich solid tumors
      implanted in mice and eliminated toxic side effects of doxorubicin.

PMID- 27044539
TI  - Noninvasive strategies for breast cancer early detection.
AB  - Breast cancer screening and presurgical diagnosis are currently based on
      mammography, ultrasound and more sensitive imaging technologies; however,
      noninvasive biomarkers represent both a challenge and an opportunity for early
      detection of cancer. An extensive number of potential breast cancer biomarkers
      have been discovered by microarray hybridization or sequencing of circulating
      DNA, noncoding RNA and blood cell RNA; multiplex analysis of immune-related
      molecules and mass spectrometry-based approaches for high-throughput detection of
      protein, endogenous peptides, circulating and volatile metabolites. However,
      their medical relevance and their translation to clinics remain to be exploited.
      Once they will be fully validated, cancer biomarkers, used in combination with
      the current and emerging imaging technologies, represent an avenue to a
      personalized breast cancer diagnosis. 

PMID- 27044540
TI  - Disease awareness in myotonic dystrophy type 1: an observational cross-sectional
      study.
AB  - BACKGROUND: Myotonic dystrophy type 1 (Steinert's disease or DM1), the most
      common form of autosomal dominant muscular dystrophy in adults, is a multisystem
      disorder, affecting skeletal muscle as well as eyes, heart, gastrointestinal
      tract, endocrine system, and central nervous system, finally responsible of
      increasing disabilities and secondary social consequences. To date, DM1-related
      brain involvement represents a challenging field of research. It is well known
      that DM1 patients frequently present neuropsychological disturbances and
      psychiatric comorbidities among which reduced awareness of disease burden and its
      progression, also defined as anosognosia, is common in clinical practice, this
      leading to secondary misattribution of symptoms, delay in timely diagnostic
      procedures and low compliance to treatment. METHODS: Here we present an
      observational cross sectional study in which disease-related cognitive
      dysfunctions and quality of life were assessed by a protocol finally designed to
      estimate the prevalence of disease awareness in a sample of 65 adult-onset DM1
      patients. RESULTS: Our analysis showed that in DM1 patients several cognitive
      functions, including executive and mnesic domains with visuo-spatial involvement,
      were affected. The assessment of anosognosia revealed that a high percentage
      (51.6%) of DM1 subjects was disease unaware. The reduced illness awareness occurs
      across different physical and life domains, and it appears more prominent in
      Activities and Independence domains investigated by the Individualized
      Neuromuscular Quality Of Life (INQoL) questionnaire. Moreover, the unawareness
      resulted significantly related (at p <0.05 and p < 0.01) to the performance
      failure in cognitive tests, specifically in the domains of visuo-spatial memory,
      cognitive flexibility and conceptualization. CONCLUSIONS: The obtained data
      confirm, by a systematic analysis, what's the common clinical perceiving of
      disease unawareness in Steinert's disease, this related to the already known
      cognitive-behavioural impairment of frontal type in affected patients. We believe
      that a deep knowledge of this aspect will be useful for medical practice in the
      management of patients with DM1, also for guidance in occupational and social
      interventions, definition of outcome measures and in preparation of trial
      readiness.

PMID- 27044541
TI  - Pain Threshold Tests in Patients With Heel Pain Syndrome.
AB  - BACKGROUND: Pressure pain threshold (PPT) is a useful tool for evaluating
      mechanical sensitivity in patients suffering from various musculoskeletal
      disorders. However, no previous study has investigated PPT in the heel of
      patients experiencing plantar heel pain syndrome (PHPS). The aim of this study
      was to compare PPT levels and topographic presentation of sensitivity in the heel
      of patients with PHPS and in healthy controls. METHODS: The reliability of PPT
      testing in patients with PHPS was assessed for intra- and interrater recordings.
      The PPT levels of 40 feet in each group were then assessed on 5 predetermined
      sites in the heel using a standardized measurement protocol. Patient functional
      status (FS) as measured by the Foot & Ankle Computerized Adaptive Test was
      employed as an external reference. RESULTS: Multivariate analysis of covariance
      revealed no group differences for PPTs at all sites (P = .406). Age (P = .099) or
      BMI (P = .510) did not affect PPT values, although there was an effect on gender
      (P = .006). The analysis revealed significant differences between sites (P <
      .001) demonstrating a diverse topographic distribution. In the PHPS group, PPT
      levels at the anterior/medial, posterior/medial and central sites were
      significantly lower than at the posterior/lateral and anterior/lateral sites (P <
      .05). For the control group, PPT levels at the anterior/medial site were
      significantly lower than all other sites (P < .001). CONCLUSION: No significant
      differences were found between PPT of the PHPS patients and controls, therefore,
      PPT cannot be recommended as an assessment tool for these patients. The
      topographic distribution indicated low PPT levels at the anterior/medial area of
      the heel in patients with PHPS and controls. LEVEL OF EVIDENCE: Level II,
      comparative study.

PMID- 27044542
TI  - Clinical and Operative Factors Related to Successful Revision Arthrodesis in the
      Foot and Ankle.
AB  - BACKGROUND: Arthrodesis is a common operative procedure used to manage arthritis
      and deformity in the foot and ankle. Nonunion is a possible and undesirable
      outcome in any arthrodesis surgery. Rates of nonunion in the foot and ankle
      literature range from 0% to 47% depending on the patient population and joint
      involved. Multiple factors can contribute to developing a nonunion including
      location, fixation method, tobacco use, diabetes, infection, and others. METHODS:
      The case logs of 3 foot and ankle surgeons were reviewed from January 2007 to
      September 2014 to identify nonunion arthrodesis revision cases. The patient
      factors reviewed included diabetes, inflammatory arthropathy, tobacco use,
      history of infection, nonunion elsewhere, neuropathy, Charcot arthropathy,
      posttraumatic arthritis, and prior attempt at revision arthrodesis at the same
      site. Operative records were reviewed to identify location of the nonunion,
      instrumention, use of allograft or autograft bone, use of iliac crest bone marrow
      aspirate (ICBMA) and use of orthobiologics such as bone morphogenetic protein
      (BMP) during the revision arthrodesis. Successful revision was defined as
      radiographic union on the final radiograph during follow-up. Eighty-two cases of
      revision arthrodesis were identified with an average follow-up of 16 months.
      RESULTS: The overall nonunion rate was 23%. Neuropathy and prior attempts at
      revision were identified as significant risks (P <.05) for persistent nonunion.
      Odds ratio calculated based on previous attempts at revision arthrodesis found a
      2.8-fold increase in the risk of failure for each attempt at revision.
      CONCLUSION: Revision arthrodesis for nonunion in the foot and ankle was
      successful (77%) under a variety of patient and operative conditions. Neuropathy
      was a significant patient risk factor for persistent nonunions, and we believe it
      is important to identify even in the nondiabetic patient. As the number of
      attempts at revisions increases, there is a subsequent 3-fold increase in the
      risk of persistent nonunion. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 27044544
TI  - Validation of Computational Approaches for Antiretroviral Dose Optimization.
AB  - Strategies for reducing antiretroviral doses and drug costs can support global
      access, and numerous options are being investigated. Efavirenz pharmacokinetic
      simulation data generated with a bottom-up physiologically based model were
      successfully compared with data obtained from the ENCORE I clinical trial
      (efavirenz at 400 mg once per day versus 600 mg once per day). These findings
      represent a pivotal paradigm for the prediction of pharmacokinetics resulting
      from dose reductions. Validated computational models constitute a valuable
      resource for optimizing therapeutic options and predicting complex clinical
      scenarios.

PMID- 27044543
TI  - High expression of ID family and IGJ genes signature as predictor of low
      induction treatment response and worst survival in adult Hispanic patients with B
      acute lymphoblastic leukemia.
AB  - BACKGROUND: B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic
      malignancy with poor clinical outcome and low survival rates in adult patients.
      Remission rates in Hispanic population are almost 30% lower and Overall Survival
      (OS) nearly two years inferior than those reported in other ethnic groups. Only
      61% of Colombian adult patients with ALL achieve complete remission (CR), median
      overall survival is 11.3 months and event-free survival (EFS) is 7.34 months.
      Identification of prognostic factors is crucial for the application of proper
      treatment strategies and subsequently for successful outcome. Our goal was to
      identify a gene expression signature that might correlate with response to
      therapy and evaluate the utility of these as prognostic tool in hispanic
      patients. METHODS: We included 43 adult patients newly diagnosed with B-ALL. We
      used microarray analysis in order to identify genes that distinguish poor from
      good response to treatment using differential gene expression analysis. The
      expression profile was validated by real-time PCR (RT-PCT). RESULTS: We
      identified 442 differentially expressed genes between responders and non
      responders to induction treatment. Hierarchical analysis according to the
      expression of a 7-gene signature revealed 2 subsets of patients that differed in
      their clinical characteristics and outcome. CONCLUSIONS: Our study suggests that
      response to induction treatment and clinical outcome of Hispanic patients can be
      predicted from the onset of the disease and that gene expression profiles can be
      used to stratify patient risk adequately and accurately. The present study
      represents the first that shows the gene expression profiling of B-ALL Colombian
      adults and its relevance for stratification in the early course of disease.

PMID- 27044545
TI  - Oxadiazoles Have Butyrate-Specific Conditional Activity against Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis is a global pathogen of huge importance which can
      adapt to several host niche environments in which carbon source availability is
      likely to vary. We developed and ran a phenotypic screen using butyrate as the
      sole carbon source to be more reflective of the host lung environment. We
      screened a library of ~87,000 small compounds and identified compounds which
      demonstrated good antitubercular activity against M. tuberculosis grown with
      butyrate but not with glucose as the carbon source. Among the hits, we identified
      an oxadiazole series (six compounds) which had specific activity against M.
      tuberculosis but which lacked cytotoxicity against mammalian cells.

PMID- 27044546
TI  - Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator
      Associated Pneumonia and Sepsis.
AB  - Increasing numbers of admissions for sepsis impose a heavy burden on health care
      systems worldwide, while novel therapies have proven both expensive and
      ineffective. We explored the long-term mortality and hospitalization costs after
      adjunctive therapy with intravenous clarithromycin in ventilator-associated
      pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a
      published randomized clinical trial; 100 were allocated to blind treatment with a
      placebo and another 100 to clarithromycin at 1 g daily for three consecutive
      days. Long-term mortality was recorded. The hospitalization cost was calculated
      by direct quantitation of imaging tests, medical interventions, laboratory tests,
      nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and
      enteral nutrition. Quantities were priced by the respective prices defined by the
      Greek government in 2002. The primary endpoint was 90-day mortality; cumulative
      hospitalization cost was the secondary endpoint. All-cause mortality rates on day
      90 were 60% in the placebo arm and 43% in the clarithromycin arm (P = 0.023); 141
      patients were alive on day 28, and mortality rates between days 29 and 90 were
      44.4% and 17.4%, respectively (P = 0.001). The mean cumulative costs on day 25 in
      the placebo group and in the clarithromycin group were ?14,701.10 and ?13,100.50
      per patient staying alive, respectively (P = 0.048). Respective values on day 45
      were ?26,249.50 and ?19,303.10 per patient staying alive (P = 0.011); this was
      associated with the savings from drugs other than antimicrobials. It is concluded
      that intravenous clarithromycin for three consecutive days as an adjunctive
      treatment in VAP and sepsis offers long-term survival benefit along with a
      considerable reduction in the hospitalization cost. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT00297674.).

PMID- 27044547
TI  - In Vivo Pharmacodynamic Target Investigation of Two Bacterial Topoisomerase
      Inhibitors, ACT-387042 and ACT-292706, in the Neutropenic Murine Thigh Model
      against Streptococcus pneumoniae and Staphylococcus aureus.
AB  - ACT-387042 and ACT-292706 are two novel bacterial topoisomerase inhibitors with
      broad-spectrum activity against Gram-positive and -negative bacteria, including
      methicillin-resistant Staphylococcus aureus and penicillin- and fluoroquinolone
      resistant Streptococcus pneumoniae We used the neutropenic murine thigh infection
      model to characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of these
      investigational compounds against a group of 10 S. aureus and S. pneumoniae
      isolates with phenotypic resistance to beta-lactams and fluoroquinolones. The in
      vitro activities of the two compounds were very similar (MIC range, 0.03 to 0.125
      mg/liter). Plasma pharmacokinetics were determined for each compound by using
      four escalating doses administered by the subcutaneous route. In treatment
      studies, mice had 10(7.4) to 10(8) CFU/thigh at the start of therapy with ACT
      387042 and 10(6.7) to 10(8.3) CFU/thigh at the start of therapy with ACT-292706.
      A dose-response relationship was observed with all isolates over the dose range.
      Maximal kill approached 3 to 4 log10 CFU/thigh compared to the burden at the
      start of therapy for the highest doses examined. There was a strong relationship
      between the PK/PD index AUC/MIC ratio (area under the concentration-time curve
      over 24 h in the steady state divided by the MIC) and therapeutic efficacy in the
      model (R(2), 0.63 to 0.82). The 24-h free-drug AUC/MIC ratios associated with net
      stasis for ACT-387042 against S. aureus and S. pneumoniae were 43 and 10,
      respectively. The 24-h free-drug AUC/MIC ratios associated with net stasis for
      ACT-292706 against S. aureus and S. pneumoniae were 69 and 25, respectively. The
      stasis PD targets were significantly lower for S. pneumoniae (P < 0.05) for both
      compounds. The 1-log-kill AUC/MIC ratio targets were ~2- to 4-fold higher than
      stasis targets. Methicillin, penicillin, or ciprofloxacin resistance did not
      alter the magnitude of the AUC/MIC ratio required for efficacy. These results
      should be helpful in the design of clinical trials for topoisomerase inhibitors.

PMID- 27044548
TI  - Topical Tenofovir Disoproxil Fumarate Nanoparticles Prevent HIV-1 Vaginal
      Transmission in a Humanized Mouse Model.
AB  - Preexposure prophylaxis (PrEP) with 1% tenofovir (TFV) vaginal gel has failed in
      clinical trials. To improve TFV efficacy in vaginal gel, we formulated tenofovir
      disoproxil fumarate nanoparticles in a thermosensitive (TMS) gel (TDF-NP-TMS
      gel). TDF-NPs were fabricated using poly(lactic-co-glycolic acid) (PLGA) polymer
      and an ion-pairing agent by oil-in-water emulsification. The efficacy of TDF-NP
      TMS gel was tested in humanized bone marrow-liver-thymus (hu-BLT) mice. Hu-BLT
      mice in the treatment group (Rx; n = 15) were administered TDF-NP-TMS gel
      intravaginally, having TDF at 0.1%, 0.5%, and 1% (wt/vol) concentrations, whereas
      the control (Ctr; n = 8) group received a blank TMS gel. All Rx mice (0.1% [n =
      4], 0.5% [n = 6], and 1% [n = 5]) were vaginally challenged with two
      transmitted/founder (T/F) HIV-1 strains (2.5 * 10(5) 50% tissue culture
      infectious doses). Rx mice were challenged at 4 h (0.1%), 24 h (0.5%), and 7 days
      (1%) posttreatment (p.t.) and Ctr mice were challenged at 4 h p.t. Blood was
      drawn weekly for 4 weeks postinoculation (p.i.) for plasma viral load (pVL) using
      reverse transcription-quantitative PCR. Ctr mice had positive pVL within 2 weeks
      p.i. Rx mice challenged at 4 h and 24 h showed 100% protection and no detectable
      pVL throughout the 4 weeks of follow-up (P = 0.009; Mantel-Cox test). Mice
      challenged at 7 days were HIV-1 positive at 14 days p.i. Further, HIV-1 viral RNA
      (vRNA) in vaginal and spleen tissues of Rx group mice with negative pVL were
      examined using an in situ hybridization (ISH) technique. The detection of vRNA
      was negative in all Rx mice studied. The present studies elucidate TDF-NP-TMS gel
      as a long-acting, coitus-independent HIV-1 vaginal protection modality.

PMID- 27044549
TI  - Single- and Repeated-Dose Pharmacokinetics of Ceftaroline in Plasma and Soft
      Tissues of Healthy Volunteers for Two Different Dosing Regimens of Ceftaroline
      Fosamil.
AB  - Ceftaroline fosamil (CPT-F) is currently approved for use for the treatment of
      complicated skin and soft tissue infections and community-acquired pneumonia at
      600 mg twice daily (q12h), but other dosing regimens are under evaluation. To
      date, very limited data on the soft tissue pharmacokinetics (PK) of the active
      compound, ceftaroline (CPT), are available. CPT concentrations in the plasma,
      muscle, and subcutis of 12 male healthy volunteers were measured by microdialysis
      after single and repeated intravenous administration of 600 mg CPT-F q12h or
      three times daily (q8h) in two groups of 6 subjects each. Relevant PK and
      PK/pharmacodynamic (PD) parameters were calculated and compared between groups.
      In plasma, the area under the concentration-time curve (AUC) from 0 to 24 h for
      total CPT and the cumulative percentage of the dosing interval during which the
      free drug concentrations exceeded the MIC (fTMIC) for unbound CPT for the
      currently established threshold of 1 mg/liter were significantly higher in the
      group receiving CPT-F q8h. Exposure to free drug in soft tissues was higher in
      the group receiving CPT-F q8h, but high interindividual variability in relevant
      PK parameters was observed. The mean ratios of the AUC from time zero to the end
      of the dosing interval (AUC0-tau) for free CPT in soft tissues and the AUC0-tau
      for the calculated free fraction in plasma at steady state ranged from 0.66 to
      0.75. Administration of CPT-F q8h led to higher levels of drug exposure in all
      investigated compartments. When MIC values above 1 mg/liter were assumed, the
      calculated fTMIC after dosing q12h was markedly lower than that after dosing q8h.
      The clinical implications of these differences are discussed in light of recently
      completed clinical phase III and PK/PD studies.

PMID- 27044550
TI  - Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida
      tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates.
AB  - We investigated the azole resistance mechanisms and clinical features of
      fluconazole-nonsusceptible (FNS) isolates of Candida tropicalis recovered from
      Korean surveillance cultures in comparison with fluconazole-less-susceptible
      (FLS) isolates. Thirty-five clinical isolates of C. tropicalis, comprising 9 FNS
      (fluconazole MIC, 4 to 64 MUg/ml), 12 FLS (MIC, 1 to 2 MUg/ml), and 14 control
      (MIC, 0.125 to 0.5 MUg/ml) isolates, were assessed. CDR1, MDR1, and ERG11
      expression was quantified, and the ERG11 and UPC2 genes were sequenced. Clinical
      features of 16 patients with FNS or FLS bloodstream isolates were analyzed. Both
      FNS and FLS isolates had >10-fold higher mean expression levels of CDR1, MDR1,
      and ERG11 genes than control isolates (P values of <0.02 for all). When FNS and
      FLS isolates were compared, FNS isolates had 3.4-fold higher mean ERG11
      expression levels than FLS isolates (P = 0.004), but there were no differences in
      those of CDR1 or MDR1 Of all 35 isolates, 4 (2 FNS and 2 FLS) and 28 (8 FNS, 11
      FLS, and 9 control) isolates exhibited amino acid substitutions in Erg11p and
      Upc2p, respectively. Both FNS and FLS bloodstream isolates were associated with
      azole therapeutic failure (3/4 versus 4/7) or uncleared fungemia (4/6 versus
      4/10), but FNS isolates were identified more frequently from patients with
      previous azole exposure (6/6 versus 3/10; P = 0.011) and immunosuppression (6/6
      versus 3/10; P = 0.011). These results reveal that the majority of FNS C.
      tropicalis isolates show overexpression of CDR1, MDR1, and ERG11 genes, and
      fungemia develops after azole exposure in patients with immunosuppression.

PMID- 27044551
TI  - Results from the Solithromycin International Surveillance Program (2014).
AB  - Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced
      activity against macrolide-resistant bacteria due to interaction with three
      ribosomal sites) and the first fluoroketolide, was tested against a 2014
      collection of 6,115 isolates, including Streptococcus pneumoniae (1,713
      isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577),
      Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by
      reference broth microdilution methods. The geographic samples included 2,748
      isolates from the United States, 2,536 from Europe, 386 from Latin America, and
      445 from the Asia-Pacific region. Solithromycin was observed to be very active
      against S. pneumoniae (MIC50/90, 0.008/0.12 MUg/ml), demonstrating 2-fold greater
      activity than telithromycin (MIC50/90, 0.015/0.25 MUg/ml) and 16- to >256-fold
      greater activity than azithromycin (MIC50/90, 0.12/>32 MUg/ml), with all strains
      being inhibited at a solithromycin MIC of <=1 MUg/ml. Against H. influenzae,
      solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2
      MUg/ml), and both of these compounds were 2-fold less active than azithromycin
      (MIC50/90, 0.5/1 MUg/ml). All but one of the M. catarrhalis isolates were
      inhibited by solithromycin at <=0.25 MUg/ml. Solithromycin inhibited 85.3% of S.
      aureus isolates at <=1 MUg/ml, and its activity was lower against methicillin
      resistant (MIC50/90, 0.06/>32 MUg/ml) than against methicillin-susceptible
      (MIC50/90, 0.06/0.06 MUg/ml) isolates. Little variation in solithromycin activity
      was observed by geographic region for the species tested. Solithromycin was very
      active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 MUg/ml), and all
      isolates were inhibited at MIC values of <=0.5 MUg/ml. In conclusion,
      solithromycin demonstrated potent activity against global and contemporary (2014)
      pathogens that represent the major causes of community-acquired bacterial
      pneumonia. These data support the continued clinical development of solithromycin
      for the treatment of this important indication.

PMID- 27044552
TI  - Enzymes Enhance Biofilm Removal Efficiency of Cleaners.
AB  - Efficient removal of biofilms from medical devices is a big challenge in health
      care to avoid hospital-acquired infections, especially from delicate devices like
      flexible endoscopes, which cannot be reprocessed using harsh chemicals or high
      temperatures. Therefore, milder solutions such as enzymatic cleaners have to be
      used, which need to be carefully developed to ensure efficacious performance. In
      vitro biofilm in a 96-well-plate system was used to select and optimize the
      formulation of novel enzymatic cleaners. Removal of the biofilm was quantified by
      crystal violet staining, while the disinfecting properties were evaluated by a
      BacTiter-Glo assay. The biofilm removal efficacy of the selected cleaner was
      further tested by using European standard (EN) for endoscope cleaning EN ISO
      15883, and removal of artificial blood soil was investigated by treating TOSI
      (Test Object Surgical Instrument) cleaning indicators. Using the process
      described here, a novel enzymatic endoscope cleaner was developed, which removed
      95% of Staphylococcus aureus and 90% of Pseudomonas aeruginosa biofilms in the 96
      well plate system. With a >99% reduction of CFU and a >90% reduction of
      extracellular polymeric substances, this cleaner enabled subsequent complete
      disinfection and fulfilled acceptance criteria of EN ISO 15883. Furthermore, it
      efficiently removed blood soil and significantly outperformed comparable
      commercial products. The cleaning performance was stable even after storage of
      the cleaner for 6 months. It was demonstrated that incorporation of appropriate
      enzymes into the cleaner enhanced performance significantly.

PMID- 27044553
TI  - Novel Cytomegalovirus UL54 DNA Polymerase Gene Mutations Selected In Vitro That
      Confer Brincidofovir Resistance.
AB  - Eight in vitro selection experiments under brincidofovir pressure elicited the
      known cytomegalovirus DNA polymerase amino acid substitutions N408K and V812L and
      the novel exonuclease domain substitutions D413Y, E303D, and E303G, which
      conferred ganciclovir and cidofovir resistance with 6- to 11-fold resistance to
      brincidofovir or 17-fold when E303G was combined with V812L. The new exonuclease
      domain I resistance mutations selected under brincidofovir pressure add to the
      single instance previously reported and show the expected patterns of cross
      resistance.

PMID- 27044554
TI  - Linking Murine and Human Plasmodium falciparum Challenge Models in a
      Translational Path for Antimalarial Drug Development.
AB  - Effective progression of candidate antimalarials is dependent on optimal dosing
      in clinical studies, which is determined by a sound understanding of
      pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important
      translational models for antimalarials have been developed: the
      NOD/SCID/IL2Rgamma(-/-) (NSG) model, whereby mice are engrafted with noninfected
      and Plasmodium falciparum-infected human erythrocytes, and the induced blood
      stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was
      used to directly measure the PK/PD in both models, which were compared to
      previously published trial data for malaria patients. The clinical part was a
      single-center, controlled study using a blood-stage Plasmodium falciparum
      challenge inoculum in volunteers to characterize the effectiveness of mefloquine
      against early malaria. The study was conducted in three cohorts (n = 8 each)
      using different doses of mefloquine. The characteristic delay in onset of action
      of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory
      concentrations (IC50s) were estimated at 2.0 MUg/ml and 1.8 MUg/ml in the NSG and
      IBSM models, respectively, aligning with 1.8 MUg/ml reported previously for
      patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for
      the 10- and 15-mg/kg doses, within the range of previously reported clinical data
      for patients but significantly lower than observed in the mouse model. Linking
      mouse and human challenge models to clinical trial data can accelerate the
      accrual of critical data on antimalarial drug activity. Such data can guide large
      clinical trials required for development of urgently needed novel antimalarial
      combinations. (This trial was registered at the Australian New Zealand Clinical
      Trials Registry [http://anzctr.org.au] under registration number
      ACTRN12612000323820.).

PMID- 27044555
TI  - Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae
      Bloodstream Infections.
AB  - Previous studies reported decreased mortality in patients with carbapenemase
      producing Klebsiella pneumoniae bloodstream infections (BSIs) treated with
      combination therapy but included carbapenem-susceptible and -intermediate
      isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients
      with BSIs caused by phenotypically carbapenem-resistant K. pneumoniae (CRKP)
      according to the number of in vitro active agents received and whether an
      extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an
      extended-spectrum cephalosporin was administered. We retrospectively reviewed
      CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates
      had meropenem or imipenem MICs of >=4 MUg/ml. Univariate and multivariable models
      were created to identify factors associated with mortality. Of 141 CRKP BSI
      episodes, 23% were treated with a single active agent (SAA), 26% were treated
      with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23%
      were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of
      >=16 MUg/ml. Thirty-day mortality was 33% overall and did not significantly
      differ across the four treatment groups in a multivariable model (P = 0.4);
      mortality was significantly associated with a Pitt bacteremia score of >=4 (odds
      ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and
      immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04).
      Individual treatment characteristics were also not significantly associated with
      outcome, including use of SAAs versus MAA (26% versus 38%, P = 0.1) or BL versus
      no BL (26% versus 39%, P = 0.1). In summary, in patients with CRKP BSIs caused by
      isolates with high carbapenem MICs, the role of combination therapy remains
      unclear, highlighting the need for prospective studies to identify optimal
      treatment regimens.

PMID- 27044556
TI  - In Vitro Activity of Eravacycline against Carbapenem-Resistant Enterobacteriaceae
      and Acinetobacter baumannii.
AB  - Eravacycline and comparators were tested against carbapenem- and tigecycline
      resistant Enterobacteriaceae and Acinetobacter isolates received at the United
      Kingdom's national reference laboratory. Eravacycline MICs correlated closely
      with those of tigecycline but mostly were around 2-fold lower; both molecules
      retained full activity against isolates with high-level tetracycline and
      minocycline resistance. MIC90s of eravacycline and tigecycline were raised ca. 2
      fold for carbapenem-resistant Enterobacteriaceae compared with carbapenem
      susceptible controls, probably reflecting subsets of isolates with increased
      efflux.

PMID- 27044558
TI  - Fight-flight or freeze-hide? Personality and metabolic phenotype mediate
      physiological defence responses in flatfish.
AB  - Survival depends on appropriate behavioural and physiological responses to
      danger. In addition to active 'fight-flight' defence responses, a passive 'freeze
      hide' response is adaptive in some contexts. However, the physiological
      mechanisms determining which individuals choose a given defence response remain
      poorly understood. We examined the relationships among personality, metabolic
      performance and physiological stress responses across an environmental gradient
      in the olive flounder, Paralichthys olivaceus. We employed four behavioural
      assays to document the existence of two distinct behavioural types ('bold' and
      'shy') in this species. We found consistent metabolic differences between
      individuals of a given behavioural type across an environmental gradient: shy
      individuals had overall lower aerobic scope, maximum metabolic rate and standard
      metabolic rate than bold individuals in both high (25 ppt) and low (3 ppt)
      salinity. These behavioural and metabolic differences translated into divergent
      physiological responses during acute stress: shy individuals adopted a passive
      'freeze-hide' response by reducing their oxygen consumption rates (akin to
      shallow breathing) whereas bold individuals adopted an active 'fight-flight'
      response by increasing their rates of respiration. These distinct defence
      strategies were repeatable within individuals between salinity treatments.
      Although it has been suggested theoretically, this is the first empirical
      evidence that the metabolic response to stressful situations differs between bold
      and shy individuals. Our results emphasize the importance of incorporating
      physiological measures to understand the mechanisms driving persistent inter
      individual differences in animals.

PMID- 27044557
TI  - Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind,
      placebo-controlled, phase II trial.
AB  - BACKGROUND: Thiamine is a vitamin that is essential for adequate aerobic
      metabolism. The objective of this study was to determine if thiamine
      administration prior to coronary artery bypass grafting would decrease post
      operative lactate levels as a measure of increased aerobic metabolism. METHODS:
      We performed a randomized, double-blind, placebo-controlled trial of patients
      undergoing coronary artery bypass grafting. Patients were randomized to receive
      either intravenous thiamine (200 mg) or placebo both immediately before and again
      after the surgery. Our primary endpoint was post-operative lactate levels.
      Additional endpoints included pyruvate dehydrogenase activity, global and
      cellular oxygen consumption, post-operative complications, and hospital and
      intensive care unit length of stay. RESULTS: Sixty-four patients were included.
      Thiamine levels were significantly higher in the thiamine group as compared to
      the placebo group immediately after surgery (1200 [683, 1200] nmol/L vs. 9 [8,
      13] nmol/L, p < 0.001). There was no difference between the groups in the primary
      endpoint of lactate levels immediately after the surgery (2.0 [1.5, 2.6] mmol/L
      vs. 2.0 [1.7, 2.4], p = 0.75). Relative pyruvate dehydrogenase activity was lower
      immediately after the surgery in the thiamine group as compared to the placebo
      group (15% [11, 37] vs. 28% [15, 84], p = 0.02). Patients receiving thiamine had
      higher post-operative global oxygen consumption 1 hour after the surgery
      (difference: 0.37 mL/min/kg [95% CI: 0.03, 0.71], p = 0.03) as well as cellular
      oxygen consumption. We found no differences in clinical outcomes. CONCLUSIONS:
      There were no differences in post-operative lactate levels or clinical outcomes
      between patients receiving thiamine or placebo. Post-operative oxygen consumption
      was significantly increased among patients receiving thiamine. TRIAL
      REGISTRATION: clinicaltrials.gov NCT02322892, December 14, 2014.

PMID- 27044559
TI  - Voriconazole combined with low-dose amphotericin B liposome for treatment of
      cryptococcal meningitis.

PMID- 27044560
TI  - Neutrophil gelatinase-associated lipocalin elimination by renal replacement
      therapy: minding the membrane!

PMID- 27044561
TI  - Two cases of severe hypokalemia in explosion victims.

PMID- 27044562
TI  - Construction of a metabolomics profile of arsenic trioxide effect in gastric
      carcinoma cell line SGC7901.
AB  - Arsenic trioxide (ATO) is highly effective for treating acute promyelocytic
      leukemia. It also holds the promise for treating solid tumors, including gastric
      carcinoma. However, the molecular mechanism of the effectiveness of ATO to solid
      tumor is still poorly understood. In this study, we chosed gastric carcinoma as
      an example and tried to reveal the antitumor mechanism through metabolomics.
      Gastric carcinoma cell line SGC7901 was treated with ATO for 6, 12, and 24 h. The
      global metabolite profiles were monitored by metabolomics analysis using gas
      chromatography (GC)/mass spectrometry (MS) and liquid chromatography/MS/MS. A
      total of 281 certified metabolites were reliably detected. Bioinformatics
      analysis showed that glycerophospholipid synthesis, one-carbon synthesis, and
      glutathione synthesis were affected dramatically. Other cellular
      functions/pathways that had been affected included inflammatory response,
      nicotinamide adenine dinucleotide (NAD(+)), and polyamine biosynthesis pathway.
      The metabolomics data from this study, in combination with previous
      transcriptomics and proteomics data, could serve as valuable resources for the
      understanding of the specific antitumor mechanism of ATO treatment. 

PMID- 27044563
TI  - Downregulation of myosin VI reduced cell growth and increased apoptosis in human
      colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide,
      with the mortality increasing steadily over the last decade. Myosin VI (MYO6)
      expression is found to be elevated in some types of human carcinoma cell types,
      suggesting that it may be a sensitive biomarker for the diagnosis and follow-up.
      In this study, we first used the Oncomine database to explore the expression of
      MYO6 in CRC tissues, and then constructed a plasmid of RNA interference targeting
      MYO6 gene. After transfection of lentivirus targeting MYO6 into SW1116 cells,
      cell viability and proliferation were measured with 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide and colony formation assay. Cell cycle
      distribution was assayed by flow cytometry and apoptosis was evaluated by Annexin
      V. MYO6 expression was detected by quantitative real-time polymerase chain
      reaction and western blot analysis. It was found that MYO6 mRNA was upregulated
      in CRC tissues using data mining of public Oncomine microarray datasets.
      Depletion of MYO6 significantly inhibited cell proliferation and colony
      formation. In addition, knockdown of MYO6 slightly arrested cell cycle in G0/G1
      phase, but remarkably increased the proportion of the sub-G1 phase of cell with
      the increase of apoptotic cells. These results suggest that MYO6 may promote cell
      growth and may be used as a potential target for anticancer therapy of CRC. 

PMID- 27044564
TI  - Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian
      Diabetics But Not Chagas Disease Patients.
AB  - Autonomic dysfunction is common in Chagas disease and diabetes. Patients with
      either condition complicated by cardiac autonomic dysfunction face increased
      mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary
      light reflexes (PLRs) may identify such patients early, allowing for intensified
      treatment. To evaluate the significance of PLRs, adults were recruited from the
      outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching
      hospital. After testing for Chagas disease and diabetes, participants completed
      conventional autonomic testing (CAT) evaluating their cardiovascular responses to
      Valsalva, deep breathing, and orthostatic changes. PLRs were measured using
      specially designed goggles, then CAT and PLRs were compared as measures of
      autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas
      disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly
      different between Chagas disease patients and controls. Patients with diabetes
      had longer latency to onset of pupil constriction, slower maximum constriction
      velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs
      correlated poorly with CAT results. A PLR-based clinical risk score demonstrated
      a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction
      compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%,
      specificity 61.3%). PLRs represent a promising tool for evaluating subclinical
      neuropathy in patients with diabetes without symptomatic autonomic dysfunction.
      Pupillometry does not have a role in the evaluation of Chagas disease patients.

PMID- 27044565
TI  - Follow-up of the 1977 Georgia Outbreak of Toxoplasmosis.
AB  - In 1977, an outbreak of toxoplasmosis occurred among 37 persons associated with
      exposure to an indoor horse arena. Cat feces containing the organism were most
      likely stirred up when horses ran on the dirt floor, and were inhaled or ingested
      by riders and observers. After 25 or more years, we attempted to locate persons
      from the outbreak and offer them an eye examination. Of the 37 persons in the
      outbreak, 18 (49%) were located; four had died, and the remaining 14 agreed to an
      examination. Among the 14 persons examined, three (21%) were found to have
      lesions typical of toxoplasmic retinochoroiditis. If these three persons were the
      only ones with ocular disease among the 37 persons in the outbreak, the disease
      rate would still be high (8%). As a result of exposure to Toxoplasma gondii
      during this outbreak, a relatively high percentage of persons developed ocular
      disease.

PMID- 27044566
TI  - Simple Identification of Human Taenia Species by Multiplex Loop-Mediated
      Isothermal Amplification in Combination with Dot Enzyme-Linked Immunosorbent
      Assay.
AB  - For differential detection of Taenia solium, Taenia saginata, and Taenia
      asiatica, loop-mediated isothermal amplification (LAMP) assay targeting the
      cytochrome c oxidase subunit 1 gene has been recently developed and shown to be
      sensitive, specific, and effective. However, to achieve differential
      identification, one specimen requires three reaction mixtures containing a primer
      set of each Taenia species separately, which is complex and time consuming and
      increases the risk of cross-contamination. In this study, we developed a simple
      differential identification of human Taenia species using multiplex LAMP (mLAMP)
      in combination with dot enzyme-linked immunosorbent assay (dot-ELISA). Forward
      inner primers of T. solium, T. saginata, and T. asiatica labeled with fluorescein
      isothiocyanate (FITC), digoxigenin (DIG), and tetramethylrhodamine (TAMRA),
      respectively, and biotin-labeled backward inner primers were used in mLAMP. The
      mLAMP assay succeeded in specific amplification of each respective target gene in
      a single tube. Furthermore, the mLAMP product from each species was easily
      distinguished by dot-ELISA with an antibody specific for FITC, DIG, or TAMRA. The
      mLAMP assay in combination with dot-ELISA will make identification of human
      Taenia species simpler, easier, and more practical.

PMID- 27044567
TI  - Leptospirosis Seroprevalence Among Blue Metal Mine Workers of Tamil Nadu, India.
AB  - Leptospirosis is mainly considered an occupational disease, prevalent among
      agriculture, sewage works, forestry, and animal slaughtering populations.
      However, putative risk to miners and their inclusion in the high-risk
      leptospirosis group remain in need of rigorous analysis. Therefore, a study was
      conducted with the objective to assess the leptospirosis seroprevalence among
      miners of two districts of Tamil Nadu, India. A total of 244 sera samples from
      Pudukkottai miners (124) and Karur miners (120) were analyzed by microscopic
      agglutination test. Antibodies to leptospires were detected in 94 samples giving
      an overall seroprevalence of 38.5%. The seroprevalence was higher among
      Pudukkottai miners (65.3%) when compared with Karur miners (10.8%).
      Seroprevalence among control population (13%) was significantly less than that of
      the Pudukkottai miners marking a possible high-risk population group distinction.
      Subject sera most commonly reacted with organisms of the serogroup Autumnalis,
      and the pattern was similar in carrier animals of the study areas. Two
      leptospires were isolated from kidney samples of rats. The prevalence of
      Autumnalis among rodents and humans source tracked human leptospirosis among the
      miners. The study also determined that Pudukkottai miners are subjected to high
      risk challenges such as exposure to water bodies on the way to the mines (odds
      ratio [OR] = 10.6), wet mine areas (OR = 10.6), rat infestation (OR = 4.6), and
      cattle rearing (OR = 10.4) and are thus frequently exposed to leptospirosis
      compared with Karur miners. Hence, control strategies targeting these populations
      will likely to prove to be effective remediation strategies benefiting
      Pudukkottai miners and workers in similar environments across occupations.

PMID- 27044568
TI  - Molecular Epidemiology of Blood-Borne Human Parasites in a Loa loa-, Mansonella
      perstans-, and Plasmodium falciparum-Endemic Region of Cameroon.
AB  - The study of the interactions among parasites within their hosts is crucial to
      the understanding of epidemiology of disease and for the design of effective
      control strategies. We have conducted an assessment of infections with Loa loa,
      Mansonella perstans, Wuchereria bancrofti, and Plasmodium falciparum in eastern
      Cameroon using a highly sensitive and specific quantitative polymerase chain
      reaction assay using archived dried whole blood spots. The resident population (N
      = 1,085) was parasitized with M. perstans (76%), L. loa (39%), and P. falciparum
      (33%), but not with W. bancrofti Compared with single infections (40.1%),
      coinfection was more common (48.8%): 21.0% had L. loa-M. perstans
      (Ll(+)/Mp(+)/Pf(-)), 2.7% had L. loa-P. falciparum (Ll(+)/Pf(+)/Mp(-)), 15.1% had
      M. perstans-P. falciparum (Mp(+)/Pf(+)/Ll(-)), and 10.0% had L. loa-M. perstans
      P. falciparum (Ll(+)/Mp(+)/Pf(+)). Interestingly, those with all three infections
      (Ll(+)/Mp(+)/Pf(+)) had significantly higher L. loa microfilaria (mf) counts than
      either single Ll(+) (P = 0.004) or double Ll(+)/Mp(+) (P = 0.024) infected
      individuals. Of those infected with L. loa, the mean estimated counts of L. loa
      mf varied based on location and were positively correlated with estimated
      intensities of M. perstans mf. Finally, at a community level, heavy L. loa
      infections were concentrated in a few individuals whereby they were likely the
      major reservoir for infection.

PMID- 27044569
TI  - Complementary and alternative medicine use by patients receiving curative-intent
      chemotherapy.
AB  - AIM: To determine which types of complementary and alternative medicine (CAM) are
      being used by cancer patients commencing curative-intent chemotherapy, whether
      the CAM taken has the potential to affect treatment efficacy, the reasons for
      patients' decisions to use CAM and whether these patients would like information
      on CAM safety with chemotherapy. METHODS: Seventy-five solid tumor malignancy
      patients receiving curative-intent treatment attending a cancer care day unit
      were interviewed about their CAM use on the day of receiving their first dose of
      chemotherapy. RESULTS: Sixty percent of study participants were using CAM at the
      start of chemotherapy treatment. Biologically active CAM assessed as having
      potential to interact with prescribed chemotherapy was ingested by 27% of
      patients, all of whom had routinely used CAM prior to cancer diagnosis. CAM was
      used by 51% of patients for supportive care reasons and by 28% of patients with
      the intention of treating their cancer. Patients' CAM decision-making was
      influenced by advice from family and friends, practitioners and casual
      acquaintances. Thirteen percent of patients were told by a CAM advice-giver not
      to have chemotherapy. The majority of patients (84%) would have liked to receive
      information on which CAM is safe to use with chemotherapy before treatment
      commenced. CONCLUSIONS: Patients being treated with curative intent, particularly
      those with a history of CAM use, may be taking biologically active CAM with
      potential to compromise their chemotherapy treatment. These patients want cancer
      care health professionals to provide them evidence-based information on safe CAM
      use with chemotherapy and may be contending with alternative health advice to not
      have chemotherapy.

PMID- 27044570
TI  - Incisional and Parastomal Hernia following Radical Cystectomy and Urinary
      Diversion: The University of Southern California Experience.
AB  - PURPOSE: Hernia is a common complication following radical cystectomy and urinary
      diversion. We investigated the clinical and radiological evidence for parastomal
      and incisional hernias, and their risk factors in a large cohort. MATERIALS AND
      METHODS: Using an institutional review board approved prospective database we
      reviewed the records of 1,101 patients who underwent radical cystectomy from 2003
      to 2013. Followup (median 57 months) was available for 670 patients. Of the 670
      patients 92 underwent ileal conduit diversion using Turnbull stomas with a median
      followup 34 months. Patients were followed with computerized tomography cancer
      surveillance. Standardized criteria were used to define parastomal and incisional
      hernias by an expert radiologist. Multivariate logistic regression was done to
      identify independent predictors. RESULTS: Parastomal hernia was diagnosed in 21
      of 92 patients (23%) with a mean age at diagnosis of 76.5 years. Incisional
      hernia was present in 125 of 670 patients (18.7%) with a mean age at diagnosis of
      68.6 years. Five patients had both hernia types. Of patients with parastomal and
      incisional hernias 11 (53%) and 111 (88.8%), respectively, were male. Mean body
      mass index was 27.5 and 27.3 kg/m(2) in patients with parastomal and incisional
      hernias, respectively. Mean parastomal and incisional defect sizes were 3.8 and
      2.4 cm, respectively. In 18 patients (85%) parastomal hernias were clinically and
      radiologically evident, 5 patients were symptomatic and 2 underwent repair. In 51
      patients (40%) incisional hernias were clinically and radiologically evident, 34
      were symptomatic and 48 underwent repair. Multivariate logistic regression showed
      significant associations of incisional hernia with age, gender, incision length,
      orthotopic diversion and body mass index. Parastomal hernia had no significant
      association. CONCLUSIONS: Hernia is common after cystectomy and diversion. Age,
      gender, body mass index, incision length and diversion type are risk factors for
      incisional hernia. Multi-institutional prospective studies may better identify
      patients at high risk.

PMID- 27044571
TI  - A 10-Item Checklist Improves Reporting of Critical Procedural Elements during
      Transurethral Resection of Bladder Tumor.
AB  - PURPOSE: Previous studies have demonstrated significant variation in recurrence
      rates after transurethral resection of bladder tumor, likely due to differences
      in surgical quality. We sought to create a framework to define, measure and
      improve the quality of transurethral resection of bladder tumor using a surgical
      checklist. MATERIALS AND METHODS: We formed a multi-institutional group of
      urologists with expertise with bladder cancer and identified 10 critical items
      that should be performed during every high quality transurethral bladder tumor
      resection. We prospectively implemented a 10-item checklist into practice and
      reviewed the operative reports of such resections performed before and after
      implementation. Results at all institutions were combined in a meta-analysis to
      estimate the overall change in the mean number of items documented. RESULTS: The
      operative notes for 325 transurethral bladder tumor resections during checklist
      use were compared to those for 428 performed before checklist implementation.
      Checklist use increased the mean number of items reported from 4.8 to 8.0 per
      resection, resulting in a mean increase of 3.3 items (95% CI 1.9-4.7) on meta
      analysis. With the checklist the percentage of reports that included all 10 items
      increased from 0.5% to 27% (p <0.0001). Surgeons who reported more checklist
      items tended to have a slightly higher proportion of biopsies containing muscle,
      although not at conventional significance (p = 0.062). CONCLUSIONS: The use of a
      10-item checklist during transurethral resection of bladder tumor improved the
      reporting of critical procedural elements. Although there was no clear impact on
      the inclusion of muscle in the specimen, checklist use may enhance surgeon
      attention to important aspects of the procedure and be a lever for quality
      improvement.

PMID- 27044572
TI  - In-hospital mortality and successful weaning from venoarterial extracorporeal
      membrane oxygenation: analysis of 5,263 patients using a national inpatient
      database in Japan.
AB  - BACKGROUND: The mortality rate of severely ill patients treated with venoarterial
      extracorporeal membrane oxygenation (VA-ECMO) remains unknown because of
      differences in patient background, clinical settings, and sample sizes between
      studies. We determined the in-hospital mortality of VA-ECMO patients and the
      proportion weaned from VA-ECMO using a national inpatient database in Japan.
      METHODS: Patients aged >= 19 years who received VA-ECMO during hospitalization
      for cardiogenic shock, pulmonary embolism, hypothermia, poisoning, or trauma
      between 1 July 2010 and 31 March 2013 were identified, using The Japanese
      Diagnosis Procedure Combination national inpatient database. RESULTS: The primary
      outcome was in-hospital mortality and the secondary outcome was the proportion
      weaned from VA-ECMO. A total of 5263 patients received VA-ECMO during the study
      period. The majority of patients had cardiogenic shock (n = 4,658). The number of
      patients weaned from VA-ECMO was 3389 (64.4%) and in-hospital mortality after
      weaning from VA-ECMO was 1994 (37.9%). In-hospital mortality without cardiac
      arrest in the cardiogenic shock group was significantly lower than that in
      patients with cardiac arrest (70.5% vs. 77.1%, p <0.001). In the multivariable
      logistic regression including multiple imputation, higher age and greater or
      smaller body mass index were significantly associated with in-hospital mortality,
      whereas hospital volume was not associated with such mortality. CONCLUSIONS: The
      present nationwide study showed high mortality rates in patients who received VA
      ECMO, and in particular in patients with cardiogenic shock and in patients with
      cardiac arrest. Weaning from VA-ECMO did not necessarily result in survival.
      Further studies are warranted to clarify risk-adjusted mortality of VA-ECMO using
      more detailed data on patient background.

PMID- 27044573
TI  - Disease dynamics and costly punishment can foster socially imposed monogamy.
AB  - Socially imposed monogamy in humans is an evolutionary puzzle because it requires
      costly punishment by those who impose the norm. Moreover, most societies were-
      and are--polygynous; yet many larger human societies transitioned from polygyny
      to socially imposed monogamy beginning with the advent of agriculture and larger
      residential groups. We use a simulation model to explore how interactions between
      group size, sexually transmitted infection (STI) dynamics and social norms can
      explain the timing and emergence of socially imposed monogamy. Polygyny dominates
      when groups are too small to sustain STIs. However, in larger groups, STIs become
      endemic (especially in concurrent polygynist networks) and have an impact on
      fertility, thereby mediating multilevel selection. Punishment of polygynists
      improves monogamist fitness within groups by reducing their STI exposure, and
      between groups by enabling punishing monogamist groups to outcompete polygynists.
      This suggests pathways for the emergence of socially imposed monogamy, and
      enriches our understanding of costly punishment evolution.

PMID- 27044574
TI  - Dead space closure with quilting suture versus conventional closure with drainage
      for the prevention of seroma after mastectomy for breast cancer (QUISERMAS):
      protocol for a multicentre randomised controlled trial.
AB  - INTRODUCTION: Postoperative wound seroma is common after mastectomy. This
      complication is associated with significant impact on patient outcomes and
      healthcare costs. The optimal closure approach for seroma prevention remains
      unknown but some evidence suggests that quilting suture of the dead space could
      lower the incidence of seroma. The aim of this trial is to compare seroma
      formation using quilting suture versus conventional closure with drainage in
      patients undergoing mastectomy. METHODS AND ANALYSIS: This is a multicentre,
      superiority, randomised controlled trial in women undergoing mastectomy with or
      without axillary involvement. Exclusion criteria include indication of bilateral
      mastectomy or immediate reconstruction and any physical or psychiatric condition
      that could impair patient's ability to cooperate with postoperative data
      collection or that do not allow an informed consent. 320 participants will be
      randomised in a 1:1 ratio to receive either quilting suture or conventional wound
      closure with drain. The primary outcome is seroma requiring either aspiration or
      surgical intervention within 21 days following mastectomy. Secondary outcomes
      include seroma regardless of whether or not it requires an intervention, surgical
      site infection, pain score, cosmetic result, patient's quality of life, costs and
      cost-effectiveness. The primary analysis will be an intention-to treat analysis
      performed with a chi(2) test (or Fisher's exact test). ETHICS AND DISSEMINATION:
      Written informed consent will be obtained from all participants. This study was
      approved by Tours Research ethics committee (CPP TOURS-Region Centre-Ouest 1,
      2014-R20, 16 December 2014). Study findings will be published in peer-reviewed
      journals and presented at relevant national and international breast cancer
      conferences. TRIAL REGISTRATION NUMBER: NCT02263651.

PMID- 27044575
TI  - Realist evaluation of the antiretroviral treatment adherence club programme in
      selected primary healthcare facilities in the metropolitan area of Western Cape
      Province, South Africa: a study protocol.
AB  - INTRODUCTION: Suboptimal retention in care and poor treatment adherence are key
      challenges to antiretroviral therapy (ART) in sub-Saharan Africa. Community-based
      approaches to HIV service delivery are recommended to improve patient retention
      in care and ART adherence. The implementation of the adherence clubs in the
      Western Cape province of South Africa was with variable success in terms of
      implementation and outcomes. The need for operational guidelines for its
      implementation has been identified. Therefore, understanding the contexts and
      mechanisms for successful implementation of the adherence clubs is crucial to
      inform the roll-out to the rest of South Africa. The protocol outlines an
      evaluation of adherence club intervention in selected primary healthcare
      facilities in the metropolitan area of the Western Cape Province, using the
      realist approach. METHODS AND ANALYSIS: In the first phase, an exploratory study
      design will be used. Document review and key informant interviews will be used to
      elicit the programme theory. In phase two, a multiple case study design will be
      used to describe the adherence clubs in five contrastive sites. Semistructured
      interviews will be conducted with purposively selected programme implementers and
      members of the clubs to assess the context and mechanisms of the adherence clubs.
      For the programme's primary outcomes, a longitudinal retrospective cohort
      analysis will be conducted using routine patient data. Data analysis will involve
      classifying emerging themes using the context-mechanism-outcome (CMO)
      configuration, and refining the primary CMO configurations to conjectured CMO
      configurations. Finally, we will compare the conjectured CMO configurations from
      the cases with the initial programme theory. The final CMOs obtained will be
      translated into middle range theories. ETHICS AND DISSEMINATION: The study will
      be conducted according to the principles of the declaration of Helsinki (1964).
      Ethics clearance was obtained from the University of the Western Cape.
      Dissemination will be done through publications and curation.

PMID- 27044576
TI  - Behaviour-change intervention in a multicentre, randomised, placebo-controlled
      COPD study: methodological considerations and implementation.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease is generally progressive and
      associated with reduced physical activity. Both pharmacological therapy and
      exercise training can improve exercise capacity; however, these are often not
      sufficient to change the amount of daily physical activity a patient undertakes.
      Behaviour-change self-management programmes are designed to address this,
      including setting motivational goals and providing social support. We present and
      discuss the necessary methodological considerations when integrating behaviour
      change interventions into a multicentre study. METHODS AND ANALYSIS: PHYSACTO is
      a 12-week phase IIIb study assessing the effects on exercise capacity and
      physical activity of once-daily tiotropium+olodaterol 5/5 ug with exercise
      training, tiotropium+olodaterol 5/5 ug without exercise training, tiotropium 5 ug
      or placebo, with all pharmacological interventions administered via the Respimat
      inhaler. Patients in all intervention arms receive a behaviour-change self
      management programme to provide an optimal environment for translating
      improvements in exercise capacity into increases in daily physical activity. To
      maximise the likelihood of success, special attention is given in the programme
      to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2)
      the patient, incorporating patient-evaluation/programme-evaluation measures to
      guide the Site Case Manager in the self-management intervention; and (3) quality
      assurance, to help identify and correct any problems or shortcomings in programme
      delivery and ensure the effectiveness of any corrective steps. This paper
      documents the comprehensive methods used to optimise and standardise the
      behaviour-change self-management programme used in the study to facilitate
      dialogue on the inclusion of this type of programme in multicentre studies.
      ETHICS AND DISSEMINATION: The study has been approved by the relevant
      Institutional Review Boards, Independent Ethics Committee and Competent Authority
      according to national and international regulations. The results of this study
      will be disseminated through relevant, peer-reviewed journals and international
      conference presentations. TRIAL REGISTRATION NUMBER: NCT02085161.

PMID- 27044577
TI  - Disability pension due to common mental disorders and subsequent suicidal
      behaviour: a population-based prospective cohort study.
AB  - OBJECTIVE: Adverse health outcomes, including suicide, in individuals on
      disability pension (DP) due to mental diagnoses have been reported. However,
      scientific knowledge on possible risk factors for suicidal behaviour (suicide
      attempt and suicide) in this group, such as age, gender, underlying DP diagnoses,
      comorbidity and DP duration and grade, is surprisingly sparse. This study aimed
      to investigate associations of different measures (main and secondary diagnoses,
      duration and grade) of DP due to common mental disorders (CMD) with subsequent
      suicidal behaviour, considering gender and age differences. DESIGN: Population
      based prospective cohort study based on Swedish nationwide registers. METHODS: A
      cohort of 46,515 individuals aged 19-64 years on DP due to CMD throughout 2005
      was followed-up for 5 years. In relation to different measures of DP, univariate
      and multivariate HRs and 95% CIs for suicidal behaviour were estimated by Cox
      regression. All analyses were stratified by gender and age. RESULTS: During 2006
      2010, 1036 (2.2%) individuals attempted and 207 (0.5%) completed suicide.
      Multivariate analyses showed that a main DP diagnosis of 'stress-related mental
      disorders' was associated with a lower risk of subsequent suicidal behaviour than
      'depressive disorders' (HR range 0.4-0.7). Substance abuse or personality
      disorders as a secondary DP diagnosis predicted suicide attempt in all subgroups
      (HR range 1.4-2.3) and suicide in women and younger individuals (HR range 2.6
      3.3). Full-time DP was associated with a higher risk of suicide attempt compared
      with part-time DP in women and both age groups (HR range 1.4-1.7). CONCLUSIONS:
      Depressive disorders as the main DP diagnosis and substance abuse or personality
      disorders as the secondary DP diagnosis were risk markers for subsequent suicidal
      behaviour in individuals on DP due to CMD. Particular attention should be paid to
      younger individuals on DP due to anxiety disorders because of the higher suicide
      risk.

PMID- 27044578
TI  - How do women with chronic fatigue syndrome/myalgic encephalomyelitis rate quality
      and coordination of healthcare services? A cross-sectional study.
AB  - OBJECTIVE: To test the association between self-rated health and self-rated
      degree of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and CFS/ME
      patients' assessment of quality of primary care, specialist care and coordination
      of care. DESIGN: Cross-sectional study. SETTING: Self-reported questionnaire data
      from women members of The Norwegian ME Association obtained in 2013.
      PARTICIPANTS: 431 women with CFS/ME aged 16-73 years. MAIN OUTCOME MEASURE: The
      participants' assessment of quality in primary care, specialist care and in
      coordination of care (good/very good or poor/very poor). Main explanatory
      variables: self-rated health and self-rated degree of CFS/ME. RESULTS: Quality of
      care was rated poor by 60.6% in primary care, by 47.7% in specialist care, and by
      71.2% regarding coordination of care. Poorer self-rated health increased the
      probability of rating quality in primary care poor, particularly among women 40
      years and over (OR 2.38, 95% CI 1.63 to 3.49), women with university education
      (OR 2.57, CI 1.68 to 3.94), and owing to less frequent general practitioner (GP)
      visits (OR 2.46, CI 1.60 to 3.78). Poorer self-rated health increased the
      probability of rating quality poor in specialist care (OR 1.38, CI 1.05 to 1.82),
      but not in coordination of care. A more severe CFS/ME was associated with a
      higher probability of rating quality in primary care poor (OR 0.61, CI 0.38 to
      0.93). Frequent visitors and those with a long GP relationship were less likely
      to report primary care quality as poor. CONCLUSIONS: A large proportion of women
      with CFS/ME rated quality of care poor/very poor in primary care, specialist care
      and in coordination of care. The dissatisfaction was higher for primary care than
      for specialist care. Overall, poorer self-rated health and a more severe CFS/ME
      were associated with lower quality scores in primary and specialist care, but not
      in coordination of care. Healthcare services, as assessed by women with CFS/ME,
      do have a large potential for improvement.

PMID- 27044579
TI  - Is health impact assessment useful in the context of trade negotiations? A case
      study of the Trans Pacific Partnership Agreement.
AB  - OBJECTIVE: The Trans Pacific Partnership Agreement (TPP) is a recently concluded
      free trade agreement involving Australia and 11 other Pacific-rim nations, which
      has the potential for far-reaching impacts on public health. A health impact
      assessment (HIA) was carried out during the negotiations to determine the
      potential future public health impact in Australia and to provide recommendations
      to mitigate potential harms. This paper explores the findings and outcomes of the
      HIA, and how this approach can be used to provide evidence for public health
      advocacy. DESIGN: A modified version of the standard HIA process was followed.
      The HIA was led by technical experts in HIA, trade policy, and health policy, in
      collaboration with advocacy organisations concerned with the TPP and health. The
      HIA reviewed the provisions in leaked TPP text in order to determine their
      potential impact on future health policy. As part of this process, researchers
      developed policy scenarios in order to examine how TPP provisions may affect
      health policies and their subsequent impact to health for both the general and
      vulnerable populations. The four policy areas assessed were the cost of
      medicines, tobacco control, alcohol control and food labelling. RESULTS: In all
      areas assessed, the HIA found that proposed TPP provisions were likely to
      adversely affect health. These provisions are also likely to more adversely
      affect the health of vulnerable populations. CONCLUSIONS: The HIA produced
      relevant evidence that was useful in advocacy efforts by stakeholders, and
      engaging the public through various media platforms.

PMID- 27044580
TI  - Counterfeit medicines in Peru: a retrospective review (1997-2014).
AB  - OBJECTIVE: To consolidate and assess information on counterfeit medicines subject
      to pharmaceutical alerts issued by the Peruvian Medicines Regulatory Authority
      over 18 years (1997-2014) of health monitoring and enforcement. DESIGN: A
      retrospective review of drug alerts. SETTING: A search of the website of the
      General Directorate of Medicines, Supplies and Drugs (DIGEMID) of the Ministry of
      Health of Peru for drug alerts issued between 1997 and 2014. ELIGIBILITY
      CRITERIA: Drug alerts related to counterfeit medicines. RESULTS: A total of 669
      DIGEMID alerts were issued during the study period, 354 (52.91%) of which cover
      1738 cases of counterfeit medicines (many alerts deal with several cases at a
      time). 1010 cases (58.11%) involved pharmaceutical establishments and 349
      (20.08%) involved non-pharmaceutical commercial outlets. In 126 cases (7.25%),
      counterfeit medicines were seized in an unauthorised trade (without any marketing
      authorisation); in 253 cases (14.56%) the type of establishment or business
      associated with the seized product was not identified. CONCLUSIONS: Counterfeit
      medicines are a serious public health problem in Peru. A review of the data
      cannot determine whether counterfeit medicines in Peru increased during the study
      period, or if monitoring by different government health agencies highlighted the
      magnitude of the problem by providing more evidence. The problem is clearly
      structural, since the majority of cases (58.11% of the total) were detected in
      legitimate supply chains. Most counterfeit medicines involve staple
      pharmaceutical products and common dosage forms. Considerable work remains to be
      done to control the serious problem of counterfeit medicines in Peru.

PMID- 27044581
TI  - Prevalence of cardiovascular health and its relationship with job strain: a cross
      sectional study in Taiwanese medical employees.
AB  - OBJECTIVES: To explore the prevalence and associated factors of cardiovascular
      health as defined by the AHA among different job categories in health settings.
      METHODS: This is a cross-sectional and hospital-based survey. A total of 1329
      medical professionals with a mean age of 38 years in a regional hospital in
      Taiwan were recruited. Information for seven combined indicators including blood
      pressure, fasting sugar, blood cholesterol, body mass index, time of physical
      activity, dietary pattern and smoking status was obtained from the employees'
      health profiles and questionnaires. Degree of job strain was evaluated by the
      Chinese version of the Job Content Questionnaire, which was derived from
      Karasek's demand-control model. Three types of cardiovascular health were
      identified as poor, intermediate and ideal. RESULTS: Prevalence of cardiovascular
      health in this study's population was ideal in 0.2% of the sample, intermediate
      in 20.6% and poor in 79.2%. There was a significantly higher percentage of poor
      health in workers with high strain (85.1%), and in the professions of nurse
      (85.3%) and physician assistant (83.1%). In the multivariate analysis, the only
      significant factor correlated with job strain was physical inactivity. After
      being adjusted, workers with high strain exhibit a higher prevalence of physical
      inactivity compared to those with low strain (OR 1.9, 95% CI 1.38 to -2.81).
      CONCLUSIONS: Physical inactivity is the only significant factor correlated with
      job strain and is associated with a work situation characterised by high strain
      and the professions of nurse and physician assistant. Strategies for workplace
      health promotion should focus on employee health literacy and motivation to
      exercise regularly.

PMID- 27044582
TI  - Factors associated with polypharmacy and excessive polypharmacy in older people
      with intellectual disability differ from the general population: a cross
      sectional observational nationwide study.
AB  - OBJECTIVES: (1) To evaluate the prevalence of polypharmacy (5-9 medicines) and
      excessive polypharmacy (10+ medicines) and (2) to determine associated
      demographic and clinical characteristics in an ageing population with
      intellectual disabilities (IDs). DESIGN: Observational cross-sectional study.
      SETTING: Wave One (2009/2010) of the Intellectual Disability Supplement to the
      Irish Longitudinal Study on Ageing (IDS-TILDA). PARTICIPANTS: A nationally
      representative sample of 753 persons with ID, aged between 41 and 90 years.
      Participants/proxy reported medicines (prescription and over the counter) taken
      on a regular basis; medication data was available for 736 participants (98%).
      MAIN OUTCOME MEASURES/INTERVENTIONS: Participants were divided into those with no
      polypharmacy (0-4 medicines), polypharmacy (5-9 medicines) and excessive
      polypharmacy (10+ medicines). Medication use patterns were analysed according to
      demographic variables and reported chronic conditions. A multinomial logistic
      regression model identified factors associated with polypharmacy (5-9 medicines)
      and excessive polypharmacy (>=10 medicines). RESULTS: Overall, 90% of
      participants reported use of medicines. Polypharmacy was observed in 31.5% of
      participants and excessive polypharmacy in 20.1%. Living in a residential
      institution, and reporting a mental health or neurological condition were
      strongly associated with polypharmacy and excessive polypharmacy after adjusting
      for confounders, but age or gender had no significant effect. CONCLUSIONS:
      Polypharmacy was commonplace for older adults with ID and may be partly explained
      by the high prevalence of multimorbidity reported. Review of appropriateness of
      medication use is essential, as polypharmacy places ageing people with ID at risk
      of adverse effects.

PMID- 27044583
TI  - Quality of relationships as predictors of outcomes in people with dementia: a
      systematic review protocol.
AB  - INTRODUCTION: Serious adverse outcomes for people with dementia include
      institutionalisation, hospitalisation, death, development of behavioural and
      psychiatric symptoms, and reduced quality of life. The quality of the
      relationship between the person with dementia and their informal/family carer is
      thought to affect the risk of these outcomes. However, little is known about
      which aspects of relationship quality are important, or how they affect outcomes
      for people with dementia. METHODS AND ANALYSIS: This will be a systematic review
      of the literature. Electronic databases MEDLINE, EMBASE, Web of Science,
      PsycInfo, the Cochrane Database, ALOIS and OpenGrey will be searched from
      inception. 2 independent reviewers will screen results for eligibility with
      standardised criteria. Data will be extracted for relevant studies, and
      information on the associations between relationship quality and dementia
      outcomes will be synthesised. Meta-analysis will be performed if possible to
      calculate pooled effect sizes. Narrative synthesis will be performed if study
      heterogeneity rules out meta-analysis. ETHICS AND DISSEMINATION: Ethical review
      is not necessary as this review summarises data from previous studies. Results
      will be disseminated via peer-reviewed publication. Results will also be
      disseminated to a patient and public involvement group and an expert panel for
      their views on the findings and implications for future work. TRIAL REGISTRATION
      NUMBER: CRD42015020518.

PMID- 27044584
TI  - Adherence to evidence-based drug therapies after myocardial infarction: is
      geographic variation related to hospital of discharge or primary care providers?
      A cross-classified multilevel design.
AB  - OBJECTIVES: To measure the adherence to polytherapy after myocardial infarction
      (MI), to compare the proportions of variation attributable to hospitals of
      discharge and to primary care providers, and to identify determinants of
      adherence to medications. SETTING: This is a population-based study. Data were
      obtained from the Information Systems of the Lazio Region, Italy (5 million
      inhabitants). PARTICIPANTS: Patients hospitalised with incident MI in 2007-2010.
      OUTCOME MEASURE: The outcome was chronic polytherapy after MI. Adherence was
      defined as a medication possession ratio >=0.75 for at least three of the
      following drugs: antiplatelets, beta-blockers, ACEI angiotensin receptor
      blockers, statins. DESIGN AND ANALYSIS: A 2-year cohort study was performed.
      Cross-classified multilevel models were applied to analyse geographic variation
      and compare proportions of variability attributable to hospitals of discharge and
      primary care providers. The variance components were expressed as median ORs
      MORs. If the MOR is 1.00, there is no variation between clusters. If there is
      considerable between-cluster variation, the MOR will be large. RESULTS: A total
      of 9606 patients were enrolled. About 63% were adherent to chronic polytherapy.
      Adherence was higher for patients discharged from cardiology wards (OR=1.56 vs
      other wards, p<0.001) and for patients with general practitioners working in
      group practice (OR=1.14 vs single-handed, p=0.042). A relevant variation in
      adherence was detected between local health districts (MOR=1.24, p<0.001). When
      introducing the hospital of discharge as a cross-classified level, the variation
      between local health districts decreased (MOR=1.13, p=0.020) and the variability
      attributable to hospitals of discharge was significantly higher (MOR=1.37,
      p<0.001). CONCLUSIONS: Secondary prevention pharmacotherapy after MI is not
      consistent with clinical guidelines. The relevant geographic variation raises
      equity issues in access to optimal care. Adherence was influenced more by the
      hospital that discharged the patient than by the primary care providers. Cross
      classified models proved to be a useful tool for defining priority areas for more
      targeted interventions.

PMID- 27044585
TI  - Effects of exercise intensity and nutrition advice on myocardial function in
      obese children and adolescents: a multicentre randomised controlled trial study
      protocol.
AB  - INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it,
      lifestyle-related diseases in children and adolescents. High-intensity interval
      training (HIIT) has recently been explored as an alternate to traditional
      moderate-intensity continuous training (MICT) in adults with chronic disease and
      has been shown to induce a rapid reversal of subclinical disease markers in obese
      children and adolescents. The primary aim of this study is to compare the effects
      of HIIT with MICT on myocardial function in obese children and adolescents.
      METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese
      children and adolescents in the cities of Trondheim (Norway) and Brisbane
      (Australia). The trial will examine the efficacy of HIIT to improve
      cardiometabolic outcomes in obese children and adolescents. Participants will be
      randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3)
      nutrition advice. Participants will partake in supervised exercise training
      and/or nutrition sessions for 3 months. Measurements for study end points will
      occur at baseline, 3 months (postintervention) and 12 months (follow-up). The
      primary end point is myocardial function (peak systolic tissue velocity).
      Secondary end points include vascular function (flow-mediated dilation
      assessment), quantity of visceral and subcutaneous adipose tissue, myocardial
      structure and function, body composition, cardiorespiratory fitness, autonomic
      function, blood biochemistry, physical activity and nutrition. Lean, healthy
      children and adolescents will complete measurements for all study end points at
      one time point for comparative cross-sectional analyses. ETHICS AND
      DISSEMINATION: This randomised controlled trial will generate substantial
      information regarding the effects of exercise intensity on paediatric obesity,
      specifically the cardiometabolic health of this at-risk population. It is
      expected that communication of results will allow for the development of more
      effective evidence-based exercise prescription guidelines in this population
      while investigating the benefits of HIIT on subclinical markers of disease. TRIAL
      REGISTRATION NUMBER: NCT01991106.

PMID- 27044586
TI  - Patient attitudes about the clinical use of placebo: qualitative perspectives
      from a telephone survey.
AB  - OBJECTIVES: To examine qualitative responses regarding the use of placebo
      treatments in medical care in a sample of US patients.Survey studies suggest a
      deliberate clinical use of placebos by physicians, and prior research has found
      that although most US patients find placebo use acceptable, the rationale for
      these beliefs is largely unknown. SETTING: Members of the Outpatient Clinic at
      the Kaiser Permanente Northern California interviewed research participants who
      had been seen for a chronic health problem at least once in the prior 6 months.
      PARTICIPANTS: 853 women (61%) and men, white (58%) and non-white participants
      aged 18-75 years. PRIMARY AND SECONDARY OUTCOMES: Qualitative responses on
      perceptions of placebo use from one-time telephone surveys were analysed for
      common themes and associations with demographic variables. RESULTS: Prior results
      indicated that a majority of respondents felt it acceptable for doctors to
      recommend placebo treatments. Our study found that a lack of harm (n=291, 46.1%)
      and potential benefit (n=250, 39.6%) were the most common themes to justify
      acceptability of placebo use. Responses citing potential benefit were associated
      with higher education (r=0.787; p<0.024). Of the minority of respondents who
      judged it never acceptable for doctors to recommend placebo treatments, the most
      often referenced rationale was obligation of the doctor to do more (n=102,
      48.3%). Additional themes emerged around the issue of whether a doctor was
      transparent about placebo use, including honesty, patient's right to know and
      power of the mind. Older age was associated with likelihood to cite overall
      physician, as opposed to treatment, related themes (r=0.753; p<0.002).
      CONCLUSIONS: Participants seem to appreciate and understand the lack of harm and
      potential benefit associated with placebo treatments, while valuing the role of
      the physician and the patient in its implementation.

PMID- 27044587
TI  - Glycosylated haemoglobin for screening and diagnosis of gestational diabetes
      mellitus.
AB  - OBJECTIVES: The oral glucose tolerance test (OGTT) is a cumbersome test that is
      time consuming, labour intensive and often poorly tolerated by pregnant women. To
      date, glycosylated haemoglobin (HbA1c) is the most accepted measure of chronic
      glycaemia outside of pregnancy. HbA1c is an uncomplicated test, less time
      consuming, does not require any specific patient preparation and is considered
      straightforward compared with the OGTT. Therefore, we prospectively tested the
      utility of the HbA1c when used as a screening tool in pregnancy for gestational
      diabetes mellitus (GDM). SETTINGS: Primary health care. Single tertiary referral
      centre, Tasmania, Australia. PARTICIPANTS: A direct comparison between HbA1c
      levels and the OGTT results in pregnant women, tested concurrently at the 24-28
      gestational week, was undertaken. A full profile of 480 pregnant women during the
      period from September 2012 to July 2014 was completed. Median and mean age of
      participants was 29 years (range 18-47 years). INTERVENTIONS: A simultaneous
      prospective assessment of HbA1c versus standard OGTT in a cohort of consecutive
      pregnant women presenting to our institute was performed. RESULTS: The number of
      women who had GDM according to OGTT criteria was 57, representing 11.9% of the
      evaluated 480 pregnant women. Using a cut-off value for HbA1c at 5.1% (32
      mmol/mol) for detecting GDM showed sensitivity of 61% and specificity of 68% with
      negative predictive value (NPV) of 93%, versus sensitivity of 27% and specificity
      of 95% with NPV of 91% when using HbA1c cut-off value of 5.4% (36 mmol/mol).
      CONCLUSIONS: Our results suggest that pregnant women with an HbA1c of>=5.4% (36
      mmol/mol) should proceed with an OGTT. This may result in a significant reduction
      in the burden of testing on both patients and testing facility staff and
      resources. Further investigations are required to integrate and optimise the
      HbA1c as a single, non-fasting, screening tool for GDM. TRIAL REGISTRATION
      NUMBER: ACTRN12611000739910.

PMID- 27044588
TI  - One week's holiday sun exposure induces expression of photoaging biomarkers.
AB  - INTRODUCTION: Skin aging is accompanied by the upregulation of the expression of
      various matrix metalloproteinases (MMPs). It was shown that exposure to
      ultraviolet radiation (UVR) may induce skin expression of MMPs and dysregulation
      of the transforming growth factor beta (TGF-beta)/Smad pathway. The aim of our
      study was to compare the effects of short holiday UVR exposure and lifetime UVR
      exposure, on the expression of MMP-8, TGF-beta1, and Smad2 in human skin
      biopsies. MATERIAL AND METHODS: Skin biopsies were taken from the outer upper arm
      of 15 elderly people with significant photoaging (mean age 64.1 years) (Group 1)
      and from 15 healthy young adult volunteers (mean age 24.1 y) who participated in
      a six-day sun holiday. Biopsies were taken twice: 24 hours before leaving for
      holiday (Group 2a) and 24 hours after returning (Group 2b). The expression of TGF
      beta1, Smad2, and MMP-8 was examined by immunochemistry and measured
      semiquantitatively by two independent pathologists. RESULTS: The mean expression
      of TGF-beta1 in dermal fibroblasts and keratinocytes in Group 1 and Group 2b was
      significantly lower than in Group 2a (0.54% +/- 0.44% and 0.48% +/- 0.51% vs.
      1.48% +/- 0.72%, respectively). The percentage of Smad2 (+) cells in Group 1 and
      Group 2b was lower than in Group 2a (2.13% +/- 1.39% and 1.81% +/- 1.16% vs.
      4.13% +/- 1.58%, respectively). The MMP-8 expression in Group 2b was 1.36% +/-
      0.68% and was significantly higher than in Group 1 (0.34% +/- 0.42%) and Group 2a
      in which the protein was not detected (p < 0.001). CONCLUSIONS: We conclude that
      the decrease in the expression of TGF-beta1 and Smad2 is a persistent biomarker
      of skin photoaging, while the increased expression of MMP-8 in keratinocytes can
      be regarded as a marker of acute sun exposure.

PMID- 27044589
TI  - Distribution of cocaine- and amphetamine-regulated transcript (CART),
      neuropeptide Y (NPY) and galanin (GAL) in the pterygopalatine ganglion of the
      domestic duck (Anas platyrhynchos f. domestica).
AB  - INTRODUCTION: Cocaine- and amphetamine-regulated transcript (CART), neuropeptide
      Y (NPY) and galanin (GAL) act as neurotransmitters and neuromodulators in both
      the central and peripheral nervous systems. Their presence has been found in
      different taxonomic groups, in particular in mammals. However, only few
      investigators have studied these neuropeptides in the class Aves (birds). The aim
      of the present study was to describe the distribution of CART, NPY and GAL in the
      pterygopalatine ganglion (PPG) of the domestic duck (Anas platyrhynchos f.
      domestica). MATERIAL AND METHODS: The experiment was conducted on 16 one-year-old
      domestic ducks of the Pekin breed of both sexes (8 males and 8 females). Frozen
      sections of the PPG were subjected to immunofluorescence staining using primary
      mouse monoclonal antibodies directed against CART and GAL and rabbit polyclonal
      antibody directed against NPY. Secondary antibodies were conjugated with Cy3 and
      FITC fluorochromes. RESULTS: CART, NPY, and GAL were present in the PPG of the
      domestic duck. The highest immunoreactivity (IR) in the ganglionic cells was
      found for CART in the majority (83-85%) of neurons of both superior (SPPG) and
      inferior (IPPG) PPG. CART-IR was also found in small aggregations of neurons on
      the medial surface of the Harderian gland, and on the course of the palatine
      branch of the facial nerve. CART-IR was also observed in the nerve fibers of
      these neurons' aggregations; however, it was low in comparison to the
      immunoreactivity of the perikarya. Immunoreactivity of NPY was found in
      ganglionic neurons, but above all in numerous fibers of the SPPG and IPPG and
      within aggregations on the surface of the Harderian gland. NPY-IR cells were
      distributed irregularly over the cross-sections of the tested aggregations, and
      constituted from 36% to 43% of the SPPG and from 37% to 40% of the IPPG of all
      cross-sectioned neurons. GAL-immunoreactive perikarya, distributed irregularly
      across the sections, were observed in the SPPG, where they constituted 61-65%,
      and in the IPPG, where they made up 50-57% of all neurons. All immunoreactive
      neurons were characterized by immunopositive neuroplasm and immunonegative cell
      nuclei. CONCLUSIONS: The presence of CART, NPY, and GAL in the PPG of the
      domestic duck suggests that these peptides may contribute to the secretory
      innervation of the glands of the mucosa of the palate and nasal cavity, the
      Harderian gland, and the lacrimal gland.

PMID- 27044590
TI  - Gene expression profiling of human bone marrow-derived mesenchymal stem cells
      during adipogenesis.
AB  - INTRODUCTION: Adipogenesis comprises multiple processes by which mesenchymal stem
      cells differentiate into adipocytes. To increase our knowledge of the mechanism
      underlying adipogenic differentiation of human bone marrow mesenchymal stem cells
      (hMSCs), we performed full-genome gene expression microarray and gene ontology
      analyses of induced differentiation of hMSCs. MATERIAL AND METHODS: Adipogenic
      differentiation of hMSCs was induced by an adipogenic medium, and total RNA was
      extracted from undifferentiated hMSCs (day 0) and differentiated adipocytes (day
      14). Then microarray hybridization of RNA samples was performed. The GeneChip
      Operating Software was used to analyze the hybridization data to identify
      differentially expressed genes, which were performed Gene Ontology categorization
      and pathway analysis. Pathway-act-network and genes-act-network were built
      according to the Kyoto Encyclopedia of Genes and Genomes database. Some
      differentially expressed genes were subjected to qRT-PCR to verify the microarray
      data. RESULTS: We detected a total of 3,821 differentially expressed genes, of
      which 753 were upregulated and 3,068 downregulated. These genes were well
      represented in a variety of functional categories, including collagen fibril
      organization, brown fat cell differentiation, cell division, and S phase of
      mitotic cell cycle. Subsequently, pathway analysis was conducted, and significant
      pathways (from top 50) were selected for pathway-act-network analysis, which
      indicated that the mitogen-activated protein kinase (MAPK) pathway and cell cycle
      were of high degrees (> 10). Gene-act-network analysis showed that insulin-like
      growth factor 1 receptor (IGF1R), histone deacetylase 1 (HDAC1), HDAC2, MAPK13,
      MAPK8, phosphoinositide-3-kinase regulatory subunit 1 (PI3KR1), and PI3KR2 also
      had high degrees (> 18). CONCLUSIONS: Collectively, these data provide novel
      information and could serve as a basis for future study to clarify the mechanisms
      underlying adipocyte differentiation of hMSCs.

PMID- 27044591
TI  - Erratum to: Understanding Brassicaceae evolution through ancestral genome
      reconstruction.

PMID- 27044592
TI  - Selumetinib for the treatment of metastatic uveal melanoma: past and future
      perspectives.
AB  - Uveal melanoma is a rare but aggressive subtype of melanoma. Nearly 50% of
      patients will develop metastatic disease despite primary enucleation or radiation
      therapy. There is currently no standard of care therapy for metastatic uveal
      melanoma, and no therapy that has been shown to prolong overall survival. Uveal
      melanoma is characterized by activation of signaling pathways including the MAPK
      pathway and the PI3K/AKT pathway, among others, via mutations in the G-alpha
      proteins GNAQ and GNA11. MEK inhibition with selumetinib has been evaluated as a
      therapeutic strategy in metastatic uveal melanoma. This review will discuss
      preclinical and clinical studies evaluating selumetinib in metastatic uveal
      melanoma, as well as potential future perspectives on MEK inhibition in the
      management of metastatic uveal melanoma. 

PMID- 27044594
TI  - New sandwich-type lanthanide complexes based on closed-macrocyclic Schiff base
      and phthalocyanine molecules.
AB  - Two new sandwich-type lanthanide complexes with the general formula
      [(Pc)2Ln3(L)(OAc)(OCH3)2] (Ln(3+) = Dy(3+) () and Er(3+) ()) were successfully
      synthesized and structurally characterized based on closed-macrocyclic Schiff
      base and phthalocyanine molecules. The magnetic properties and structure-property
      relationship in this multi-decker system were investigated. Interestingly, the
      corresponding dysprosium complex shows typical single-molecule magnetic behavior
      with ferromagnetic dipole-dipole interactions and the slow relaxation of
      magnetization.

PMID- 27044593
TI  - Meaning making in long-term care: what do certified nursing assistants think?
AB  - Certified nursing assistants (CNAs) provide up to 80% of the direct care to older
      adults in long-term care facilities. CNAs are perceived as being at the bottom of
      the hierarchy among healthcare professionals often negatively affecting their job
      satisfaction. However, many CNAs persevere in providing quality care and even
      reporting high levels of job satisfaction. The aim of the present investigation
      was to identify primary themes that may help CNAs make meaning of their chosen
      career; thus potentially partially explaining increases in job satisfaction among
      this group. Focus groups were conducted with CNAs at three long-term care
      facilities. Four themes emerged from the data: CNA work is good or special; CNA
      as relationship builder; CNA as expert; CNA as team member. These themes reflect
      the perceptions that these CNAs held in regard to themselves and their
      relationships to others in the work environment and, when present, can contribute
      to intrinsic job satisfaction. Our meaning-making themes support the premise that
      CNAs do not passively accept the evaluations of others but instead actively frame
      identities that validate their importance to residents and the institution.

PMID- 27044595
TI  - Regulatory roles of Oct proteins in the mammary gland.
AB  - The expression of Oct-1 and -2 and their binding to the octamer motif in the
      mammary gland are developmentally and hormonally regulated, consistent with the
      expression of milk proteins. Both of these transcription factors constitutively
      bind to the proximal promoter of the milk protein gene beta-casein and might be
      involved in the inhibition or activation of promoter activity via interactions
      with other transcription factors or cofactors at different developmental stages.
      In particular, the lactogenic hormone prolactin and glucocorticoids induce Oct-1
      and Oct-2 binding and interaction with both the signal transducer and activator
      of transcription 5 (STAT5) and the glucocorticoid receptor on the beta-casein
      promoter to activate beta-casein expression. In addition, increasing evidence has
      shown the involvement of another Oct factor, Oct-3/4, in mammary tumorigenesis,
      making Oct-3/4 an emerging prognostic marker of breast cancer and a molecular
      target for the gene-directed therapeutic intervention, prevention and treatment
      of breast cancer. This article is part of a Special Issue entitled: The Oct
      Transcription Factor Family, edited by Dr. Dean Tantin. 

PMID- 27044596
TI  - Does caffeine reduce postoperative bowel paralysis after elective laparoscopic
      colectomy? (CaCo trial): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Postoperative bowel paralysis is common after abdominal operations,
      including colectomy. As a result, hospitalization may be prolonged, thereby
      leading to increased cost. A recent randomized controlled trial showed that the
      consumption of regular black coffee after colectomy is associated with a
      significantly faster resumption of intestinal motility. The mechanism by which
      coffee stimulates intestinal motility is unknown, but caffeine seems to be the
      most likely stimulating agent. Thus, the effect of caffeine on postoperative
      bowel activity after colon surgery will be analyzed in this trial, herein
      referred to as CaCo. METHODS/DESIGN: Patients scheduled for elective laparoscopic
      colectomy or upper rectum resection are eligible to participate in this double
      blinded, placebo-controlled, randomized trial. Patients fulfilling all inclusion
      criteria will be allocated after the surgical procedure to one of three treatment
      arms: 100 mg caffeine, 200 mg caffeine, or placebo (corn starch). Patients will
      take the capsules containing the study medication three times daily with a meal.
      The primary endpoint of the study is the time to a solid bowel movement. The
      study treatment will be stopped after the patient produces a solid bowel movement
      or has taken ten capsules, whichever occurs first. To determine the colonic
      passage time, patients will take a capsule with radiopaque markers at breakfast
      for the first 3 days after surgery. On the fourth day, the location of the
      markers will be determined with an abdominal X-ray scan. Further secondary
      objectives are the postoperative morbidity and mortality, well-being, sleeping
      behavior, and length of hospital stay. The study size was calculated to be 180
      patients with an interim analysis occurring after 60 patients. DISCUSSION: From a
      previous study investigating coffee, evidence exists that caffeine might have a
      positive influence on the postoperative bowel activity. This double-blinded,
      placebo-controlled, randomized trial tries to show that caffeine will shorten the
      postoperative bowel paralysis and, thus, will improve recovery and shorten the
      hospital stay after colon surgery. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT02510911 Swiss National Clinical Trials Portal SNCTP000001131.

PMID- 27044597
TI  - Treatment of Osteochondritis Dissecans of the Talus in Skeletally Immature
      Population: A Critical Analysis of the Available Evidence.
AB  - Juvenile osteochondritis dissecans of the talus (JOCDT) is a subchondral bone
      alteration and a partially or completely detached osteochondral fragment,
      affecting skeletally immature patients. A review of the English literature on
      PubMed was conducted. Conservative treatment was applied in patients up to Berndt
      Harty stage III. Surgical indications were conservative management failure and
      loose bodies. The most performed procedures were drilling, subchondral bone
      grafting, fragment fixation, or excision. High rate of clinical success were
      achieved, whereas radiographic results were much lower. None of the surgical
      options demonstrated to be superior. Future long-term qualitative studies
      focusing on chondral tissue restoration are needed. LEVELS OF EVIDENCE:
      Therapeutic, Level IV.

PMID- 27044598
TI  - Entrapment of the Superficial Peroneal Nerve Following a Distal Fibula Fracture.
AB  - : Although peripheral nerve injury may result from fractures involving the long
      bones, bony entrapment of peripheral nerves is infrequently encountered. This
      report demonstrates a rare case of superficial peroneal nerve entrapment between
      2 fracture ends of the distal fibula following a closed ankle fracture resulting
      from a supination-external rotation mechanism. LEVELS OF EVIDENCE: Therapeutic,
      Level IV: Case report.

PMID- 27044599
TI  - Thromboprophylaxis in Ambulatory Trauma Patients With Foot and Ankle Fractures:
      Prospective Study Using a Risk Scoring System.
AB  - Lower-limb immobilization has been implicated as an etiological factor for venous
      thromboembolic events (VTEs). However, there is no patient-centered scoring
      system available for risk assessment in ambulatory trauma patients with temporary
      lower-limb immobilization. A patient questionnaire scoring system has been
      developed for ambulatory patients with foot and ankle fracture being managed
      nonoperatively as outpatients by temporary lower-limb immobilization. Patients
      are classed as either high or low risk for developing a VTE and offered low
      molecular-weight heparin (LMWH) accordingly. This is a prospective study of 150
      patients with a follow-up of 6 months. Only 3 patients developed VTEs: one was
      noncompliant with medicine, one was started on LMWH 2 days after getting a
      plaster cast, and the third was not started on LMWH in spite of family history of
      VTEs. This study showed that using this scoring system, LMWH can be used safely
      and effectively as a thromboprophylactic agent for ambulatory trauma patients
      requiring temporary lower-limb immobilization to manage foot and ankle fractures.
      It is a step toward developing a validated clinical prediction score to enable
      risk assessment in ambulatory trauma patients who are managed non-operatively
      with temporary lower limb immobilization. LEVELS OF EVIDENCE: Prognostic, Level
      IV: Case series.

PMID- 27044600
TI  - Total Ankle Arthroplasty for the Treatment of Symptomatic Nonunion Following
      Tibiotalar Fusion.
AB  - Background Nonunion of an ankle arthrodesis is associated with significant pain
      and morbidity. Revision arthrodesis presents greater short-term morbidity and
      long-term sequelae. 1-6 Recent reports have demonstrated the feasibility of
      converting a symptomatic nonunion of an ankle arthrodesis to a total ankle
      arthroplasty.7-9 The objective of the present study was to evaluate the short
      term outcome associated with take down of symptomatic nonunions of ankle
      arthrodeses and conversion to a fixed bearing, intramedullary total ankle
      arthroplasty. Methods Five patients with symptomatic, aseptic tibiotalar
      arthrodesis nonunions (average age, 62.2 years), who underwent conversion to a
      total ankle arthroplasty were retrospectively identified and assessed at a
      prospective office visit. Minimum follow-up was 12 months (average, 21.3 months).
      Clinical outcomes were assessed on the basis of the American Foot and Ankle
      Society (AOFAS) ankle-hindfoot score10 and the Foot Function Index.11,12
      Radiographic analysis, patient satisfaction and pain levels were also evaluated.
      Results The average post-operative AOFAS ankle-hindfoot score was 82.6, while the
      FFI was 28.2%. The average clinical range of motion was 35 degrees. Visual analog
      scale (VAS) pain scores averaged 31.1 out of 100. Four out of the five patients
      were very satisfied or satisfied. Radiographically, the tibial and talar
      components were stable in all patients without evidence of loosening, migration,
      or subsidence. There were no complications requiring additional procedures.
      Conclusions Patients undergoing ankle arthrodesis that is complicated by an
      aseptic nonunion pose a difficult clinical problem. Conversion to a total ankle
      arthroplasty with a fixed bearing, intramedullary implant is a viable treatment
      option with reliable short-term results. LEVELS OF EVIDENCE: Therapeutic, Level
      IV: Case series.

PMID- 27044602
TI  - Correction.

PMID- 27044601
TI  - The resveratrol-enriched rice DJ526 boosts motor coordination and physical
      strength.
AB  - The main objective of current genetic modifications in crops is to boost
      agricultural production or to develop GM crops with an improved nutrient profile
      by introducing a new trait to the plants. A GM crop surpassing the ability of the
      introduced genetic characteristics has not been developed yet. Here, we show that
      the resveratrol-enriched rice DJ526, a GM crop, has unexpectedly high beneficial
      health effects surpassing the introduced genetic characteristic of resveratrol
      synthetic ability. The synergistic effect of its innate and transgenic properties
      not only ameliorates age-related deterioration but also boosts motor coordination
      and physical strength during the aging process. The gene expression profiling
      analyses by DNA chip showed that the gene expression pattern of mice fed
      resveratrol-enriched rice DJ526 was very different from mice fed either
      resveratrol or Dongjin rice alone, respectively, modifying expression of genes
      related to aging regulation, cell differentiation, extracellular matrix,
      neurogenesis, or secretion. 

PMID- 27044603
TI  - Consumption of sugar sweetened beverages, artificially sweetened beverages, and
      fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis,
      and estimation of population attributable fraction.
AB  - OBJECTIVES: To examine the prospective associations between consumption of sugar
      sweetened beverages, artificially sweetened beverages, and fruit juice with type
      2 diabetes before and after adjustment for adiposity, and to estimate the
      population attributable fraction for type 2 diabetes from consumption of sugar
      sweetened beverages in the United States and United Kingdom. DESIGN: Systematic
      review and meta-analysis. DATA SOURCES AND ELIGIBILITY: PubMed, Embase, Ovid, and
      Web of Knowledge for prospective studies of adults without diabetes, published
      until February 2014. The population attributable fraction was estimated in
      national surveys in the USA, 2009-10 (n=4729 representing 189.1 million adults
      without diabetes) and the UK, 2008-12 (n=1932 representing 44.7 million).
      SYNTHESIS METHODS: Random effects meta-analysis and survey analysis for
      population attributable fraction associated with consumption of sugar sweetened
      beverages. RESULTS: Prespecified information was extracted from 17 cohorts
      (38,253 cases/10,126,754 person years). Higher consumption of sugar sweetened
      beverages was associated with a greater incidence of type 2 diabetes, by 18% per
      one serving/day (95% confidence interval 9% to 28%, I(2) for heterogeneity=89%)
      and 13% (6% to 21%, I(2)=79%) before and after adjustment for adiposity; for
      artificially sweetened beverages, 25% (18% to 33%, I(2)=70%) and 8% (2% to 15%,
      I(2)=64%); and for fruit juice, 5% (-1% to 11%, I(2)=58%) and 7% (1% to 14%,
      I(2)=51%). Potential sources of heterogeneity or bias were not evident for sugar
      sweetened beverages. For artificially sweetened beverages, publication bias and
      residual confounding were indicated. For fruit juice the finding was non
      significant in studies ascertaining type 2 diabetes objectively (P for
      heterogeneity=0.008). Under specified assumptions for population attributable
      fraction, of 20.9 million events of type 2 diabetes predicted to occur over 10
      years in the USA (absolute event rate 11.0%), 1.8 million would be attributable
      to consumption of sugar sweetened beverages (population attributable fraction
      8.7%, 95% confidence interval 3.9% to 12.9%); and of 2.6 million events in the UK
      (absolute event rate 5.8%), 79,000 would be attributable to consumption of sugar
      sweetened beverages (population attributable fraction 3.6%, 1.7% to 5.6%).
      CONCLUSIONS: Habitual consumption of sugar sweetened beverages was associated
      with a greater incidence of type 2 diabetes, independently of adiposity. Although
      artificially sweetened beverages and fruit juice also showed positive
      associations with incidence of type 2 diabetes, the findings were likely to
      involve bias. None the less, both artificially sweetened beverages and fruit
      juice were unlikely to be healthy alternatives to sugar sweetened beverages for
      the prevention of type 2 diabetes. Under assumption of causality, consumption of
      sugar sweetened beverages over years may be related to a substantial number of
      cases of new onset diabetes.

PMID- 27044604
TI  - Evaluation of alpha-synuclein immunohistochemical methods for the detection of
      Lewy-type synucleinopathy in gastrointestinal biopsies.
AB  - The observation showing that Lewy type synucleinopathy (LTS), the pathological
      hallmark of Parkinson's disease (PD), is found in the gut of almost all PD
      subjects led to a substantial amount of research to develop a diagnostic
      procedure in living patients based on endoscopically obtained gastrointestinal
      biopsies. However, the existing studies have provided conflicting results
      regarding the sensitivity and specificity of gastrointestinal biopsies for the
      detection of LTS. We therefore undertook a multi-center staining and blinded
      judging of a common set of slides from colonic biopsies to determine the optimal
      protocol for the detection of LTS. Four different immunohistochemical methods,
      developed in four separate expert laboratories, were evaluated for their
      sensitivity and specificity to detect enteric LTS. Test sets of formalin-fixed,
      paraffin-embedded sections from biopsies of 9 PD subjects and 3 controls were
      stained with the 4 methods and graded by 4 different observers. Four types of
      staining morphology (granular staining in the lamina propria,
      perivascular/vascular wall staining in the submucosa, lacy-granular pattern in
      the submucosa and epithelial cell nuclear staining) were variably observed in the
      slides stained by the 4 methods. Positive alpha-synuclein staining was observed
      by all 5 judges in most of the slides from control cases, regardless of the
      staining methods that were used. Moreover, none of the tested method or staining
      pattern had a specificity and sensitivity more than 80 % regarding to PD.
      Overall, our study suggest that the tested methods are not adequate for the
      prediction of PD using gastrointestinal biopsies. Future studies are warranted to
      test new immunostaining methods. 

PMID- 27044605
TI  - Implementing Recommendations From Web Accessibility Guidelines: Would They Also
      Provide Benefits to Nondisabled Users.
AB  - OBJECTIVE: We examined the consequences of implementing Web accessibility
      guidelines for nondisabled users. BACKGROUND: Although there are Web
      accessibility guidelines for people with disabilities available, they are rarely
      used in practice, partly due to the fact that practitioners believe that such
      guidelines provide no benefits, or even have negative consequences, for
      nondisabled people, who represent the main user group of Web sites. Despite these
      concerns, there is a lack of empirical research on the effects of current Web
      accessibility guidelines on nondisabled users. METHOD: Sixty-one nondisabled
      participants used one of three Web sites differing in levels of accessibility
      (high, low, and very low). Accessibility levels were determined by following
      established Web accessibility guidelines (WCAG 2.0). A broad methodological
      approach was used, including performance measures (e.g., task completion time)
      and user ratings (e.g., perceived usability). RESULTS: A high level of Web
      accessibility led to better performance (i.e., task completion time and task
      completion rate) than low or very low accessibility. Likewise, high Web
      accessibility improved user ratings (i.e., perceived usability, aesthetics,
      workload, and trustworthiness) compared to low or very low Web accessibility.
      There was no difference between the very low and low Web accessibility conditions
      for any of the outcome measures. CONCLUSION: Contrary to some concerns in the
      literature and among practitioners, high conformance with Web accessibility
      guidelines may provide benefits to users without disabilities. APPLICATION: The
      findings may encourage more practitioners to implement WCAG 2.0 for the benefit
      of users with disabilities and nondisabled users.

PMID- 27044606
TI  - Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in
      Advanced Epithelial Ovarian Carcinoma.
AB  - Ovarian cancer is a chronic disease with a risk of malnutrition. Nutritional Risk
      Index (NRI) has been reported as a simple and accurate tool to assess the
      nutritional status. We sought to explore the prevalence of malnutrition and its
      association with survival in ovarian cancer. A retrospective study was conducted
      in 213 advanced ovarian cancer patients. NRI was calculated before and at the end
      of treatment using patients' body weight and serum albumin level. Overall
      survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier
      method, and associations were assessed using a Cox proportional hazards analysis
      adjusted for known prognostic variables. Moderate to severely malnourished
      patients had lower 5-yr OS (45.3%) compared to normal to mild group (64.0%),
      respectively (P = 0.024). Adjusted for covariates, the relative risk of death was
      5.8 times higher in moderate/severely malnourished group identified at the last
      course of chemotherapy (HR = 5.896, 95% CI = 2.723-12.764, P < 0.001). Similarly,
      this cohort had shorter PFS compared with normal to mild risk group (median 15
      vs. 28 months, P = 0.011). Malnutrition is prevalent among ovarian cancer
      patients and is found to be a significant predictor for mortality.

PMID- 27044607
TI  - A four-dimensional snapshot hyperspectral video-endoscope for bio-imaging
      applications.
AB  - Hyperspectral imaging has proven significance in bio-imaging applications and it
      has the ability to capture up to several hundred images of different wavelengths
      offering relevant spectral signatures. To use hyperspectral imaging for in vivo
      monitoring and diagnosis of the internal body cavities, a snapshot hyperspectral
      video-endoscope is required. However, such reported systems provide only about 50
      wavelengths. We have developed a four-dimensional snapshot hyperspectral video
      endoscope with a spectral range of 400-1000 nm, which can detect 756 wavelengths
      for imaging, significantly more than such systems. Capturing the three
      dimensional datacube sequentially gives the fourth dimension. All these are
      achieved through a flexible two-dimensional to one-dimensional fiber bundle. The
      potential of this custom designed and fabricated compact biomedical probe is
      demonstrated by imaging phantom tissue samples in reflectance and fluorescence
      imaging modalities. It is envisaged that this novel concept and developed probe
      will contribute significantly towards diagnostic in vivo biomedical imaging in
      the near future.

PMID- 27044608
TI  - The evolutionary origin of CIPK16: A gene involved in enhanced salt tolerance.
AB  - Calcineurin B-like protein interacting protein kinases (CIPKs) are key regulators
      of pre-transcriptional and post-translational responses to abiotic stress.
      Arabidopsis thaliana CIPK16 (AtCIPK16) was identified from a forward genetic
      screen as a gene that mediates lower shoot salt accumulation and improved
      salinity tolerance in Arabidopsis and transgenic barley. Here, we aimed to gain
      an understanding of the evolution of AtCIPK16, and orthologues of CIPK16 in other
      plant species including barley, by conducting a phylogenetic analysis of
      terrestrial plant species. The resulting protein sequence based phylogenetic
      trees revealed a single clade that included AtCIPK16 along with two segmentally
      duplicated CIPKs, AtCIPK5 and AtCIPK25. No monocots had proteins that fell into
      this clade; instead the most closely related monocot proteins formed a group
      basal to the entire CIPK16, 5 and 25 clade. We also found that AtCIPK16 contains
      a core Brassicales specific indel and a putative nuclear localisation signal,
      which are synapomorphic characters of CIPK16 genes. In addition, we present a
      model that proposes the evolution of CIPK16, 5 and 25 clade.

PMID- 27044609
TI  - The Effect of a Summer Camp Intervention on the Nutrition Knowledge and Dietary
      Behavior of Adolescent Girls.
AB  - The purpose of this study was to design a rewards-based nutrition intervention
      program to improve knowledge and dietary behaviors of adolescent girls. Our
      participants consisted of eight girls ages 11 to 13 years. Nutritional knowledge
      was assessed before and after intervention program through a "Jeopardy" style
      quiz game and posttest questionnaires. Participants were also interviewed
      throughout the week about typical dietary behaviors, daily physical activity, and
      self-esteem. Educational activities took place for 2 to 3 hours each day and
      included a grocery store scavenger hunt, healthy baking demonstrations, and relay
      races. Participants received bracelets and charms as rewards for participation in
      activities. Nutritional knowledge increased for six out of eight participants,
      although the overall increase was not found to be statistically significant (p =
      .20). Significant correlations were found between measures including dietary
      behavior (soda consumption per week and perceived importance of body weight: r = 
      .827, p = .01), self-esteem (weight and endurance: r = .801, p = .03), and
      fitness levels (weight and curl-ups completed in 30 seconds: r = -.729, p = .04).
      This study shows promising evidence that this nutrition education intervention
      could be effective at increasing nutrition knowledge, thus potentially affecting
      future dietary behaviors of adolescent girls.

PMID- 27044610
TI  - Antibiotic resistance and the refugee crisis in Europe - Preemptive action is
      indicated.

PMID- 27044611
TI  - Current situation of Crimean-Congo hemorrhagic fever in Southeastern Europe and
      neighboring countries: a public health risk for the European Union?
AB  - Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tick-borne viral
      infection of humans, occurring across western China through southern Asia, Middle
      East, and Southeastern Europe (SEE) and in the most of African countries. CCHF
      virus is maintained through vertical and horizontal transmission in several
      genera of ticks, mainly in Hyalomma, which spreads the virus to a variety of wild
      and domestic mammals, which develop a transient viremia without signs of illness.
      Human infections occur through tick bite or exposure to the blood or other body
      fluids of an infected animal or of a CCHF patient. In SEE the number of clinical
      cases of CCHF as well as the areal of the infected ticks continuously rapidly
      increased after 2000. The aim of this study was to present actual situation of
      CCHF in SEE. Sources of information include published literature and personal
      unpublished data. CONCLUSIONS: Based on: 1. Hyaloma's presence in Western EU
      countries, 2. Changes in climatic conditions and 3. Absence of an active
      vaccination against CCHF, it can be expected that this disease will continue to
      present real threat for human health in SEE and Southwestern Europe (SWE).

PMID- 27044612
TI  - Crimean-Congo hemorrhagic fever - A ticking bomb?

PMID- 27044613
TI  - Open traumatic brain injury by nail gun resulting in a persistent vegetative
      state.

PMID- 27044614
TI  - Reversible deep brain swelling causing REM behavior disorder.

PMID- 27044615
TI  - Quality improvement in neurology: Multiple sclerosis quality measures: Executive
      summary.

PMID- 27044616
TI  - Association between job strain and risk of incident stroke: A meta-analysis.

PMID- 27044617
TI  - Pearls & Oy-sters: Mitochondrial neurogastrointestinal encephalomyopathy:
      Diagnosis and response to peritoneal dialysis.

PMID- 27044618
TI  - Pearls & Oy-sters: Diagnostic challenges in nocturnal frontal lobe epilepsy.

PMID- 27044619
TI  - Teaching NeuroImages: Acute crossed cerebellar diaschisis.

PMID- 27044620
TI  - Authors' Response: DHEA supplementation and ICSI outcomes: was this really
      randomized trial?

PMID- 27044621
TI  - Hepcidin in the diagnosis of iron disorders.
AB  - The discovery of the iron-regulatory hormone hepcidin in 2001 has revolutionized
      our understanding of iron disorders, and its measurement should advance
      diagnosis/treatment of these conditions. Although several assays have been
      developed, a gold standard is still lacking, and efforts toward harmonization are
      ongoing. Nevertheless, promising applications can already be glimpsed, ranging
      from the use of hepcidin levels for diagnosing iron-refractory iron deficiency
      anemia to global health applications such as guiding safe iron supplementation in
      developing countries with high infection burden.

PMID- 27044622
TI  - Characterization of Clostridium difficile Spores Lacking Either SpoVAC or
      Dipicolinic Acid Synthetase.
AB  - The spore-forming obligate anaerobe Clostridium difficile is a leading cause of
      antibiotic-associated diarrhea around the world. In order for C. difficile to
      cause infection, its metabolically dormant spores must germinate in the
      gastrointestinal tract. During germination, spores degrade their protective
      cortex peptidoglycan layers, release dipicolinic acid (DPA), and hydrate their
      cores. In C. difficile, cortex hydrolysis is necessary for DPA release, whereas
      in Bacillus subtilis, DPA release is necessary for cortex hydrolysis. Given this
      difference, we tested whether DPA synthesis and/or release was required for C.
      difficile spore germination by constructing mutations in either spoVAC or dpaAB,
      which encode an ion channel predicted to transport DPA into the forespore and the
      enzyme complex predicted to synthesize DPA, respectively. C. difficile spoVAC and
      dpaAB mutant spores lacked DPA but could be stably purified and were more
      hydrated than wild-type spores; in contrast, B. subtilis spoVAC and dpaAB mutant
      spores were unstable. Although C. difficile spoVAC and dpaAB mutant spores
      exhibited wild-type germination responses, they were more readily killed by wet
      heat. Cortex hydrolysis was not affected by this treatment, indicating that wet
      heat inhibits a stage downstream of this event. Interestingly, C. difficile
      spoVAC mutant spores were significantly more sensitive to heat treatment than
      dpaAB mutant spores, indicating that SpoVAC plays additional roles in conferring
      heat resistance. Taken together, our results demonstrate that SpoVAC and DPA
      synthetase control C. difficile spore resistance and reveal differential
      requirements for these proteins among the Firmicutes IMPORTANCE: Clostridium
      difficile is a spore-forming obligate anaerobe that causes ~500,000 infections
      per year in the United States. Although spore germination is essential for C.
      difficile to cause disease, the factors required for this process have been only
      partially characterized. This study describes the roles of two factors, DpaAB and
      SpoVAC, which control the synthesis and release of dipicolinic acid (DPA),
      respectively, from bacterial spores. Previous studies of these proteins in other
      spore-forming organisms indicated that they are differentially required for spore
      formation, germination, and resistance. We now show that the proteins are
      dispensable for C. difficile spore formation and germination but are necessary
      for heat resistance. Thus, our study further highlights the diverse functions of
      DpaAB and SpoVAC in spore-forming organisms.

PMID- 27044623
TI  - Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate
      Reveals a Genetic Rationale for Invasive Skin Tropicity.
AB  - The genome of an invasive skin-tropic strain (AP53) of serotype M53 group A
      Streptococcus pyogenes (GAS) is composed of a circular chromosome of 1,860,554 bp
      and carries genetic markers for infection at skin locales, viz, emm gene family
      pattern D and FCT type 3. Through genome-scale comparisons of AP53 with other GAS
      genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that
      reveal a potential genetic basis for skin tropism. The genome of AP53 differed by
      ~30 point mutations from a noninvasive pattern D serotype M53 strain (Alab49), 4
      of which are located in virulence genes. One pseudogene, yielding an inactive
      sensor kinase (CovS(-)) of the two-component transcriptional regulator CovRS, a
      major determinant for invasiveness, severely attenuated the expression of the
      secreted cysteine protease SpeB and enhanced the expression of the hyaluronic
      acid capsule compared to the isogenic noninvasive AP53/CovS(+) strain. The
      collagen-binding protein transcript sclB differed in the number of 5'
      pentanucleotide repeats in the signal peptides of AP53 and Alab49 (9 versus 15),
      translating into different lengths of their signal peptides, which nonetheless
      maintained a full-length translatable coding frame. Furthermore, GAS strain AP53
      acquired two phages that are absent in Alab49. One such phage (PhiAP53.2)
      contains the known virulence factor superantigen exotoxin gene tandem speK-slaA
      Overall, we conclude that this bacterium has evolved in multiple ways, including
      mutational variations of regulatory genes, short-tandem-repeat polymorphisms,
      large-scale genomic alterations, and acquisition of phages, all of which may be
      involved in shaping the adaptation of GAS in specific infectious environments and
      contribute to its enhanced virulence. IMPORTANCE: Infectious strains of S.
      pyogenes (GAS) are classified by their serotypes, relating to the surface M
      protein, the emm-like subfamily pattern, and their tropicity toward the
      nasopharynx and/or skin. It is generally agreed that M proteins from pattern D
      strains, which also directly bind human host plasminogen, are skin tropic. We
      have sequenced and characterized the genome of an invasive pattern D GAS strain
      (AP53) in comparison to a very similar strain (Alab49) that is noninvasive and
      developed a genomic rationale as to possible reasons for the skin tropicity of
      these two strains and the greater invasiveness of AP53.

PMID- 27044624
TI  - Facilitated Dissociation of a Nucleoid Protein from the Bacterial Chromosome.
AB  - Off-rates of proteins from the DNA double helix are widely considered to be
      dependent only on the interactions inside the initially bound protein-DNA complex
      and not on the concentration of nearby molecules. However, a number of recent
      single-DNA experiments have shown off-rates that depend on solution protein
      concentration, or "facilitated dissociation." Here, we demonstrate that this
      effect occurs for the major Escherichia coli nucleoid protein Fis on isolated
      bacterial chromosomes. We isolated E. coli nucleoids and showed that dissociation
      of green fluorescent protein (GFP)-Fis is controlled by solution Fis
      concentration and exhibits an "exchange" rate constant (kexch) of ~10(4) M(-1) s(
      1), comparable to the rate observed in single-DNA experiments. We also show that
      this effect is strongly salt dependent. Our results establish that facilitated
      dissociation can be observed in vitro on chromosomes assembled in vivo
      IMPORTANCE: Bacteria are important model systems for the study of gene regulation
      and chromosome dynamics, both of which fundamentally depend on the kinetics of
      binding and unbinding of proteins to DNA. In experiments on isolated E. coli
      chromosomes, this study showed that the prolific transcription factor and
      chromosome packaging protein Fis displays a strong dependence of its off-rate
      from the bacterial chromosome on Fis concentration, similar to that observed in
      in vitro experiments. Therefore, the free cellular DNA-binding protein
      concentration can strongly affect lifetimes of proteins bound to the chromosome
      and must be taken into account in quantitative considerations of gene regulation.
      These results have particularly profound implications for transcription factors
      where DNA binding lifetimes can be a critical determinant of regulatory function.

PMID- 27044625
TI  - Laboratory Evolution of Microbial Interactions in Bacterial Biofilms.
AB  - Microbial adaptation is conspicuous in essentially every environment, but the
      mechanisms of adaptive evolution are poorly understood. Studying evolution in the
      laboratory under controlled conditions can be a tractable approach, particularly
      when new, discernible phenotypes evolve rapidly. This is especially the case in
      the spatially structured environments of biofilms, which promote the occurrence
      and stability of new, heritable phenotypes. Further, diversity in biofilms can
      give rise to nascent social interactions among coexisting mutants and enable the
      study of the emerging field of sociomicrobiology. Here, we review findings from
      laboratory evolution experiments with either Pseudomonas fluorescens or
      Burkholderia cenocepacia in spatially structured environments that promote
      biofilm formation. In both systems, ecotypes with overlapping niches evolve and
      produce competitive or facilitative interactions that lead to novel community
      attributes, demonstrating the parallelism of adaptive processes captured in the
      lab.

PMID- 27044626
TI  - Type IV Pilus Expression Is Upregulated in Nontypeable Haemophilus influenzae
      Biofilms Formed at the Temperature of the Human Nasopharynx.
AB  - Nontypeable Haemophilus influenzae (NTHI), a commensal of the human nasopharynx
      (hNP), is a common cause of biofilm-associated diseases of the respiratory tract.
      However, NTHI biofilm biology at the average hNP temperature, i.e., 34 degrees C,
      has not been well studied. Here we grew NTHI biofilms at 34 degrees C and 37
      degrees C, to evaluate relative biofilm growth, expression, and function of the
      type IV pilus (Tfp), a critical adhesin important for NTHI biofilm formation. The
      kinetics and regulation of Tfp expression in NTHI biofilms are unclear,
      especially at 34 degrees C. Tfp expression, as estimated by pilA promoter
      activity, was distributed throughout the biofilms, with a unique pattern that was
      dependent on temperature, time in culture, and position within the maturing
      biofilm. Tfp expression was required for the formation of the characteristic
      tower structures of NTHI biofilms and was significantly upregulated in NTHI
      biofilms formed at 34 degrees C versus 37 degrees C. This increase correlated
      with significantly greater twitching motility at 34 degrees C than at 37 degrees
      C. Treatment with antisera targeting the major subunit of Tfp (PilA)
      significantly inhibited NTHI biofilm formation at both temperatures, confirming
      the importance of this critical adhesin in biofilm formation. Additionally,
      treatment of preestablished biofilms with antisera against PilA significantly
      decreased biofilm biomass and mean thickness at both temperatures. These results
      demonstrated a pivotal role for Tfp in NTHI biofilm formation and stability at
      the temperature of the hNP, and they underscore the utility of PilA as a vaccine
      candidate for treatment and/or prevention of NTHI biofilm-associated diseases.
      IMPORTANCE: NTHI is an important cause of chronic respiratory tract infections,
      including otitis media, chronic rhinosinusitis, and exacerbations of chronic
      obstructive pulmonary disease and cystic fibrosis. The chronic and recurrent
      nature of these diseases is attributed to the presence of bacterial biofilms,
      which are highly resistant to antimicrobials. We characterized NTHI biofilm
      growth and expression of PilA, the major subunit of the Tfp, at the temperature
      of the hNP, which is the commensal habitat of NTHI. Our results expand the
      current understanding of the role of Tfp during biofilm formation and maturation
      at the temperature of both the hNP and the middle ear, and they strengthen
      support for PilA as a vaccine candidate for the prevention and treatment of NTHI
      biofilm-associated diseases.

PMID- 27044627
TI  - Comparative Analysis of Cellulophaga algicola and Flavobacterium johnsoniae
      Gliding Motility.
AB  - Gliding motility is common in members of the phylum Bacteroidetes, including
      Flavobacterium johnsoniae and Cellulophaga algicola. F. johnsoniae gliding has
      been extensively studied and involves rapid movement of the cell surface adhesin
      SprB. Genetic analysis of C. algicola allowed a comparative analysis of gliding.
      Sixty-three HimarEm1-induced mutants that formed nonspreading colonies were
      characterized. Each had an insertion in an ortholog of an F. johnsoniae motility
      gene, highlighting similarities between the motility systems. Differences were
      also observed. C. algicola lacks orthologs of the F. johnsoniae motility genes
      gldA, gldF, and gldG that are thought to encode the components of an ATP-binding
      cassette (ABC) transporter. In addition, mutations in any of 12 F. johnsoniae gld
      genes result in complete loss of motility, whereas all C. algicola gld mutants
      retained slight residual motility. This may indicate that C. algicola has
      multiple motility systems, that the motility proteins exhibit partial redundancy
      of function, or that essential components of the motility machinery of both C.
      algicola and F. johnsoniae remain to be discovered. IMPORTANCE: The development
      of genetic tools for C. algicola and comparative analysis of F. johnsoniae and C.
      algicola motility mutants identified similarities and differences between their
      gliding motility machineries. Gliding motility is common in the phylum
      Bacteroidetes Proteins that are important for gliding in both C. algicola and F.
      johnsoniae are potential core components of the Bacteroidetes gliding motility
      machinery.

PMID- 27044628
TI  - Proper Control of Caulobacter crescentus Cell Surface Adhesion Requires the
      General Protein Chaperone DnaK.
AB  - Growth in a surface-attached bacterial community, or biofilm, confers a number of
      advantages. However, as a biofilm matures, high-density growth imposes stresses
      on individual cells, and it can become less advantageous for progeny to remain in
      the community. Thus, bacteria employ a variety of mechanisms to control
      attachment to and dispersal from surfaces in response to the state of the
      environment. The freshwater oligotroph Caulobacter crescentus can elaborate a
      polysaccharide-rich polar organelle, known as the holdfast, which enables
      permanent surface attachment. Holdfast development is strongly inhibited by the
      small protein HfiA; mechanisms that control HfiA levels in the cell are not well
      understood. We have discovered a connection between the essential general protein
      chaperone, DnaK, and control of C. crescentus holdfast development. C. crescentus
      mutants partially or completely lacking the C-terminal substrate binding "lid"
      domain of DnaK exhibit enhanced bulk surface attachment. Partial or complete
      truncation of the DnaK lid domain increases the probability that any single cell
      will develop a holdfast by 3- to 10-fold. These results are consistent with the
      observation that steady-state levels of an HfiA fusion protein are significantly
      diminished in strains that lack the entire lid domain of DnaK. While dispensable
      for growth, the lid domain of C. crescentus DnaK is required for proper chaperone
      function, as evidenced by observed dysregulation of HfiA and holdfast development
      in strains expressing lidless DnaK mutants. We conclude that DnaK is an important
      molecular determinant of HfiA stability and surface adhesion control. IMPORTANCE:
      Regulatory control of cell adhesion ensures that bacterial cells can transition
      between free-living and surface-attached states. We define a role for the
      essential protein chaperone, DnaK, in the control of Caulobacter crescentus cell
      adhesion. C. crescentus surface adhesion is mediated by an envelope-attached
      organelle known as the holdfast. Holdfast development is tightly controlled by
      HfiA, a small protein inhibitor that directly interacts with a WecG/TagA-family
      glycosyltransferase required for holdfast biosynthesis. We demonstrate that the C
      terminal lid domain of DnaK is not essential for growth but is necessary for
      proper control of HfiA levels in the cell and for control of holdfast adhesin
      development.

PMID- 27044629
TI  - The YsrS Paralog DygS Has the Capacity To Activate Expression of the Yersinia
      enterocolitica Ysa Type III Secretion System.
AB  - The Yersinia enterocolitica Ysa type III secretion system (T3SS) is associated
      with intracellular survival, and, like other characterized T3SSs, it is tightly
      controlled. Expression of the ysa genes is only detected following growth at low
      temperatures (26 degrees C) and in high concentrations of sodium chloride (290
      mM) in the medium. The YsrSTR phosphorelay (PR) system is required for ysa
      expression and likely responds to NaCl. During our investigations into the Ysr PR
      system, we discovered that genes YE3578 and YE3579 are remarkably similar to ysrR
      and ysrS, respectively, and are probably a consequence of a gene duplication
      event. The amino acid differences between YE3578 and ysrR are primarily clustered
      into two short regions. The differences between YE3579 and ysrS are nearly all
      located in the periplasmic sensing domain; the cytoplasmic domains are 98%
      identical. We investigated whether these paralogs were capable of activating ysa
      gene expression. We found that the sensor paralog, named DygS, is capable of
      compensating for loss of ysrS, but the response regulator paralog, DygR, cannot
      complement a ysrR gene deletion. In addition, YsrR, but not DygR, interacts with
      the histidine phosphorelay protein YsrT. Thus, DygS likely activates ysa gene
      expression in response to a signal other than NaCl and provides an example of a
      phosphorelay system in which two sensor kinases feed into the same regulatory
      pathway. IMPORTANCE: All organisms need mechanisms to promote survival in
      changing environments. Prokaryotic phosphorelay systems are minimally comprised
      of a histidine kinase (HK) that senses an extracellular stimulus and a response
      regulator (RR) but can contain three or more proteins. Through gene duplication,
      a unique hybrid HK was created. We show that, while the hybrid appears to retain
      all of the phosphorelay functions, it responds to a different signal than the
      original. Both HKs transmit the signal to the same RR, which activates a promoter
      that transcribes a set of genes encoding a type III secretion system (T3SS) whose
      function is not yet evident. The significance of this work lies in finding that
      two HKs regulate this T3SS, highlighting its importance.

PMID- 27044630
TI  - Mindfulness training for smoking cessation: A meta-analysis of randomized
      controlled trials.
AB  - Recent studies have shown that mindfulness training has a promising potential for
      smoking treatment. In order to examine the efficacy of mindfulness training in
      smoking cessation, we performed a systematic review of the literature and meta
      analysis of randomized controlled trials. Four randomized controlled trials with
      474 patients were included in our analysis. The results showed that 25.2 percent
      of participants remained abstinent for more than 4 months in the mindfulness
      group compared to 13.6 percent of those who received usual care therapy (relative
      risk, 1.88; 95 percent confidence interval, 1.04-3.40). Our results suggest that
      mindfulness training may have an important role to play in efforts to lower
      cigarette smoking rates.

PMID- 27044631
TI  - Blood pressure lowering does not reduce risk of cardiovascular events in patients
      at intermediate risk.

PMID- 27044632
TI  - David Oliver: The best health system.

PMID- 27044633
TI  - Obesity and kidney disease: Beyond the hyperfiltration.
AB  - In industrialized countries, overweight and obesity account for approximately
      13.8% and 24.9% of the kidney disease observed in men and women, respectively.
      Moreover, obesity-associated glomerulopathy is now considered as "an emerging
      epidemic." Kidney function can be negatively impacted by obesity through several
      mechanisms, either direct or indirect. While it is well established that obesity
      represents the leading risk factor for type 2 diabetes and hypertension,
      awareness that obesity is associated with direct kidney damage independently of
      hypertension and diabetes is still not widespread. In this paper we will discuss
      the emerging role of adipose tissue, particularly in the visceral depot, in
      obesity-induced chronic kidney damage. 

PMID- 27044634
TI  - SNAIL gene inhibited by hypoxia-inducible factor 1alpha (HIF-1alpha) in
      epithelial ovarian cancer.
AB  - The aim of this study was to investigate the relationship between HIF-1alpha and
      SNAIL gene expression in the epithelial ovarian cancer (EOC) cell line. EOC cells
      were treated with hypoxia, hypoxia combined with rapamycin, and control. The
      expression of HIF-1alpha and E-cad were assessed by reverse transcription
      polymerase chain reaction (RT-PCR) and western blotting. The gene expression of
      SNAIL was studied by RT-PCR and real-time PCR. RNA interference technology was
      used to determine the relationship between HIF-1alpha and SNAIL. The present
      study indicated that the HIF-1alpha protein was expressed and increased in EOC
      cell line. SNAIL mRNA was found to increase and E-cad expression decreased with
      the time of hypoxia prolonged. Hypoxia increased invasion abilities of EOC cell
      line, but compared with cells exposed to hypoxia, the change of invasive ability
      of cells with rapamycin had no effect. The expression of HIF-1alpha protein and
      SNAIL mRNA could be inhibited gradually by rapamycin. siRNA of HIF-1alpha could
      suppress the expression of SNAIL while siRNA of SNAIL had no influence on HIF
      1alpha protein expression. HIF-1alpha may be the upstream of the SNAIL gene in
      EOC. Our data suggested that HIF-1alpha might be an upregulator of the SNAIL gene
      and HIF-1alpha-SNAIL-E-cad pathway may play an important role in EOC invasion and
      metastasis. 

PMID- 27044636
TI  - Correction: Cutting Edge: TRPV4-Mediated Detection of Hyposmotic Stress by Skin
      Keratinocytes Activates Developmental Immunity.

PMID- 27044635
TI  - Environmental Immunology: Lessons Learned from Exposure to a Select Panel of
      Immunotoxicants.
AB  - Exposure to environmental contaminants can produce profound effects on the immune
      system. Many classes of xenobiotics can significantly suppress or enhance immune
      responsiveness depending on the levels (i.e., dose) and context (i.e., timing,
      route) of exposure. Although defining the effects that toxicants can have on the
      immune system is a valuable component to improving public health, environmental
      immunology has greatly enhanced our understanding of how the immune system
      functions and has provided innovative avenues to explore new immunotherapies.
      This Brief Review focuses on three examples of how immunotoxicology has
      benefitted the field of immunology, presenting information on the aryl
      hydrocarbon receptor signaling pathway, the immunomodulatory effects of
      nanomaterials, and the impact of xenobiotic exposure on the developing immune
      system. Collectively, contributions from immunotoxicology have significantly
      enhanced public health and spurred seminal advances in both basic and applied
      immunology.

PMID- 27044637
TI  - Correction: SATB1 Plays a Critical Role in Establishment of Immune Tolerance.

PMID- 27044638
TI  - Doctors slam junior contract for discrimination against women.

PMID- 27044639
TI  - Creating a Community Capacity Assessment to Identify Agency Outcomes Related to
      Occupational Therapy Student Community Partnerships.
AB  - Service-learning experiences immerse students in authentic situations and build
      partnerships with community agencies to support the health of those we serve in
      practice. Most occupational therapy curriculum evaluations do not systematically
      capture community agency benefits. Through the use of qualitative interviews and
      Q Methodology, the Community Agency Capacity Questionnaire (CACQ) was developed
      to capture the agency experience in these partnerships. This paper describes the
      iterative analytic process that resulted in the CACQ with 29 statements covering
      6 domains: programming, evaluation, partnership, staff, funding, and marketing.
      The CACQ offers a means to identify outcomes from the service-learning partners'
      perspective. 

PMID- 27044640
TI  - Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for
      Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity
      Studies.
AB  - Tavaborole is a topical antifungal agent approved by the US Food and Drug
      Administration for the treatment of toenail onychomycosis. As part of the
      nonclinical development program, reproductive and developmental toxicity studies
      were conducted (rat oral fertility and early embryonic development, rat (oral)
      and rabbit (dermal) embryo-fetal development). There were no effects on fertility
      or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum
      recommended human dose [MRHD] based on mean area under the plasma concentration
      time curve comparisons). In the rat embryo-fetal development toxicity studies,
      teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD).
      However, several treatment-related skeletal malformations and variations were
      observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development
      toxicity studies dosed via oral or dermal administration, the no observable
      adverse effect level for maternal toxicity and embryo-fetal toxicity was 50
      mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively.

PMID- 27044641
TI  - Margaret McCartney: The great QOF experiment.

PMID- 27044642
TI  - Vancomycin Use: Room for Improvement Among Hospitalized Children.
AB  - INTRODUCTION: The use of vancomycin is common among hospitalized children. We
      sought to evaluate the impact of prospective audit with real-time feedback on
      vancomycin use and pharmacy costs. METHODS: Vancomycin use was evaluated at
      Monroe Carell Jr Children's Hospital at Vanderbilt (MCJCHV) before and after the
      implementation of prospective audit with intervention and feedback to providers
      in 2012. Antibiotic use was compared to academic children's hospitals with
      established antimicrobial stewardship programs (ASPs). Two similar pediatric
      academic institutions without an ASP were used as nonintervention controls.
      Analysis of monthly days of antibiotic therapy (DoT) per 1000 patient-days was
      performed by interrupted time series analysis. RESULTS: Monthly vancomycin use
      decreased from 114 DoTs/1000 patient-days to 89 DoTs/1000 patient-days ( P <
      .0001). We did not find significant differences in the slope of change in
      vancomycin use between MCJCHV and institutions with ASPs either before or after
      the intervention ( P = .86 and P = .71, respectively). When compared to
      children's hospitals without ASPs, the use of vancomycin was significantly lower
      at MCJCHV ( P < .001). CONCLUSION: The use of vancomycin at academic children's
      hospitals with an ASP is declining. In our experience, prospective audit with
      real-time intervention and feedback to providers significantly reduced the use
      and costs associated with vancomycin.

PMID- 27044643
TI  - How a pain management program for patients and spouses can benefit their lives?

PMID- 27044644
TI  - A tale of two sequences: microRNA-target chimeric reads.
AB  - In animals, a functional interaction between a microRNA (miRNA) and its target
      RNA requires only partial base pairing. The limited number of base pair
      interactions required for miRNA targeting provides miRNAs with broad regulatory
      potential and also makes target prediction challenging. Computational approaches
      to target prediction have focused on identifying miRNA target sites based on
      known sequence features that are important for canonical targeting and may miss
      non-canonical targets. Current state-of-the-art experimental approaches, such as
      CLIP-seq (cross-linking immunoprecipitation with sequencing), PAR-CLIP
      (photoactivatable-ribonucleoside-enhanced CLIP), and iCLIP (individual-nucleotide
      resolution CLIP), require inference of which miRNA is bound at each site.
      Recently, the development of methods to ligate miRNAs to their target RNAs during
      the preparation of sequencing libraries has provided a new tool for the
      identification of miRNA target sites. The chimeric, or hybrid, miRNA-target reads
      that are produced by these methods unambiguously identify the miRNA bound at a
      specific target site. The information provided by these chimeric reads has
      revealed extensive non-canonical interactions between miRNAs and their target
      mRNAs, and identified many novel interactions between miRNAs and noncoding RNAs. 

PMID- 27044645
TI  - Mutanalyst, an online tool for assessing the mutational spectrum of epPCR
      libraries with poor sampling.
AB  - BACKGROUND: Assessing library diversity is an important control step in a
      directed evolution experiment. To do this, a limited amount of colonies from a
      test library are sequenced and tested. In the case of an error-prone PCR library,
      the spectrum of the identified mutations - the proportions of mutations of a
      specific nucleobase to another- is calculated enabling the user to make more
      informed predictions on library diversity and coverage. However, the calculations
      of the mutational spectrum are severely affected by the limited sample sizes.
      RESULTS: Here an online program, called Mutanalyst, is presented, which not only
      automates the calculations, but also estimates errors involved. Specifically, the
      errors are calculated thanks to the complementarity of DNA, which means that a
      mutation has a complementary mutation on the other sequence. Additionally, in the
      case of determining the mean number of mutations per sequence it does so by
      fitting to a Poisson distribution, which is more robust than calculating the
      average in light of the small sampling size. CONCLUSION: As a result of the added
      measures to keep into account of small sample size the user can better assess
      whether the library is satisfactory or whether error-prone PCR conditions should
      be adjusted. The program is available at www.mutanalyst.com .

PMID- 27044646
TI  - Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa
      and levodopa) clinical efficacy and safety.
AB  - Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative
      disorder with progressive motor symptoms that can be managed with treatments.
      Levodopa is generally recognized as the most effective and widely used treatment
      for PD. It improves function and quality of life, morbidity, and mortality, and
      therefore reduces individual and societal costs. Levodopa has a relatively short
      half-life, however, and is quickly metabolized in the plasma, leading to
      fluctuations, including wearing-off of effect and inconsistent symptomatic relief
      as well as development of dyskinesias, with both wearing off and dyskinesias
      worsening with advancing disease. Immediate-release and controlled-release
      formulations have been used with success, but motor fluctuations remain a
      problem. RYTARY (levodopa and carbidopa, IPX066) is an oral extended-release
      therapy composed of carbidopa-levodopa microbeads designed to dissolve at various
      rates that allows for quick absorption and sustained levodopa release over an
      extended period. In development studies, RYTARY improved symptoms in patients
      with both early and advanced PD and offered significantly improved Unified
      Parkinson Disease Rating Scale scores and "on" times, without worsening
      troublesome dyskinesias when compared to other levodopa formulations.
      Tolerability and safety were comparable to other formulations. This section
      reviews the data that support the use of RYTARY in the treatment of PD. 

PMID- 27044647
TI  - Physicians' experience with RYTARY (carbidopa and levodopa) extended-release
      capsules in patients who have Parkinson disease.
AB  - A discussion between Dr. Dee Silver and Dr. Richard Trosch provides insight and
      advice for physicians considering a switch from immediate-release carbidopa
      levodopa (IR CD-LD) to RYTARY as a treatment for patients with Parkinson disease
      (PD). The dialogue describes how they identify patients with PD who may and may
      not be successful switching to RYTARY, how they approach the conversion process
      and patient compliance, and how they address some side effects that may occur
      after patients begin taking RYTARY. The clinicians also discuss their experiences
      with how long it takes to establish a stable regimen as well as provide general
      advice regarding conversion from treatment with IR CD-LD to RYTARY. 

PMID- 27044648
TI  - Levodopa therapy for Parkinson disease: A look backward and forward.
AB  - Although levodopa is widely recognized as the most effective therapy for
      Parkinson disease (PD), its introduction 5 decades ago was preceded by several
      years of uncertainty and equivocal clinical results. The translation of basic
      neuroscience research by Arvid Carlsson and Oleh Hornykiewicz provided a logical
      pathway for treating PD with levodopa. Yet the pioneering clinicians who
      transformed PD therapeutics with this drug--among them Walther Birkmayer, Isamu
      Sano, Patrick McGeer, George Cotzias, Melvin Yahr, and others--faced many
      challenges in determining whether the concept and the method for replenishing
      deficient striatal dopamine was correct. This article reviews highlights in the
      early development of levodopa therapy. In addition, it provides an overview of
      emerging drug delivery strategies that show promise for improving levodopa's
      pharmacologic limitations.

PMID- 27044649
TI  - Analysis of Differential Proteins in Two Wing-Type Females of Sogatella furcifera
      (Hemiptera: Delphacidae).
AB  - Sogatella furcifera(Horvath) is an important rice pest with the wing dimorphism,
      including macropterous and brachypterous morphs. The protein expression profiles
      in two wing-type adults and two wing-type disc fifth-instar nymphs were analyzed
      using two-dimensional gel protein electrophoresis and mass spectrometry. In
      adults and fifth-instar nymphs, 127 and 162 protein spots were detected,
      respectively. Fifty-five differentially expressed protein spots were identified
      between the long-winged adults and the short-winged adults, and 62 differentially
      expressed protein spots were found between the long-winged disc fifth-instar
      nymphs and short-winged disc fifth-instar nymphs. In long-winged and short-winged
      adults, six and seven specific protein spots were identified, respectively, with
      five and seven protein spots having more than threefold increased level,
      respectively. In long-winged and short-winged disc morph nymphs, 8 and 12
      specific protein spots were identified, respectively, with 11 and 17 spots
      containing more than threefold increased level, respectively. Among the 16
      identified proteins, five proteins are associated with muscle function,
      suggesting that muscle is a main tissue where the genes were differentially
      expressed between the two wing types. In addition, the content of a peptidase
      with an insulinase domain was higher (by 3.02 +/- 0.59 fold) in the short-winged
      fifth-instar nymphs than in the long-winged fifth-instar nymphs, which suggests
      that this peptidase may be involved in wing differentiation by regulating insulin
      receptors. The results of this study provide some genetic clues for the wing
      differential development inS. furcifera and provide more references for future
      studies.

PMID- 27044650
TI  - Anaesthesia.

PMID- 27044651
TI  - Histological findings in equine testes one year after standing laparoscopic
      peritoneal flap hernioplasty.
AB  - In order to know reproduction-related complications due to standing laparoscopic
      peritoneal flap hernioplasty, histological characteristics of the testicles from
      five stallions one year after surgery were compared with seven testicles from
      four healthy stallions. Moreover, the daily sperm output (DSO) was determined
      before (T0) and one year after surgery (T12). DSO did not show significant
      differences between T0 and T12. The diameter of the seminiferous tubules was
      significantly decreased in the samples from the hernioplasty group. The
      percentage of tubules with full spermatogenesis was smaller in the hernioplasty
      group, but the difference was not significant. It can be concluded that standing
      laparoscopic peritoneal flap hernioplasty produced mild histological changes in
      the testicular parenchyma, epididymis and pampiniform plexus after one year
      follow-up. 

PMID- 27044652
TI  - Evaluation and optimisation of propofol pharmacokinetic parameters in cats for
      target-controlled infusion.
AB  - The aim of this study was to develop and evaluate a pharmacokinetic model-driven
      infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg)
      was administered intravenously over 60 seconds to induce anaesthesia for the
      elective neutering of seven healthy cats, premedicated intramuscularly with 0.3
      mg/kg methadone, 0.01 mg/kg medetomidine and 2 mg/kg ketamine. Venous blood
      samples were collected over 240 minutes, and propofol concentrations were
      measured via a validated high-performance liquid chromatography assay. Selected
      pharmacokinetic parameters, determined by a three-compartment open linear model,
      were entered into a computer-controlled infusion pump (target-controlled infusion
      1 (TCI-1)). In a second step, TCI-1 was used to induce and maintain general
      anaesthesia in nine cats undergoing neutering. Predicted and measured plasma
      concentrations of propofol were compared at specific time points. In a third
      step, the pharmacokinetic parameters were modified according to the results from
      the use of TCI-1 and were evaluated again in six cats. For this TCI-2 group, the
      median values of median performance error and median absolute performance error
      were -1.85 per cent and 29.67 per cent, respectively, indicating that it
      performed adequately. Neither hypotension nor respiratory depression was observed
      during TCI-1 and TCI-2. Mean anaesthesia time and time to extubation in the TCI-2
      group were 73.90 (+/-20.29) and 8.04 (+/-5.46) minutes, respectively. 

PMID- 27044653
TI  - SoftPanel: a website for grouping diseases and related disorders for generation
      of customized panels.
AB  - BACKGROUND: Targeted next-generation sequencing is playing an increasingly
      important role in biological research and clinical diagnosis by allowing
      researchers to sequence high priority genes at much higher depths and at a
      fraction of the cost of whole genome or exome sequencing. However, in designing
      the panel of genes to be sequenced, investigators need to consider the tradeoff
      between the better sensitivity of a broad panel and the higher specificity of a
      potentially more relevant panel. Although tools to prioritize candidate disease
      genes have been developed, the great majority of these require prior knowledge
      and a set of seed genes as input, which is only possible for diseases with a
      known genetic etiology. RESULTS: To meet the demands of both researchers and
      clinicians, we have developed a user-friendly website called SoftPanel. This
      website is intended to serve users by allowing them to input a single disorder or
      a disorder group and generate a panel of genes predicted to underlie the disorder
      of interest. Various methods of retrieval including a keyword search, browsing of
      an arborized list of International Classification of Diseases, 10th revision (ICD
      10) codes or using disorder phenotypic similarities can be combined to define a
      group of disorders and the genes known to be associated with them. Moreover,
      SoftPanel enables users to expand or refine a gene list by utilizing several
      biological data resources. In addition to providing users with the facility to
      create a "hard" panel that contains an exact gene list for targeted sequencing,
      SoftPanel also enables generation of a "soft" panel of genes, which may be used
      to further filter a significantly altered set of genes identified through whole
      genome or whole exome sequencing. The service and data provided by SoftPanel can
      be accessed at http://www.isb.pku.edu.cn/SoftPanel/ . A tutorial page is included
      for trying out sample data and interpreting results. CONCLUSION: SoftPanel
      provides a convenient and powerful tool for creating a targeted panel of
      potential disease genes while supporting different forms of input. SoftPanel may
      be utilized in both genomics research and personalized medicine.

PMID- 27044654
TI  - The systems biology format converter.
AB  - BACKGROUND: Interoperability between formats is a recurring problem in systems
      biology research. Many tools have been developed to convert computational models
      from one format to another. However, they have been developed independently,
      resulting in redundancy of efforts and lack of synergy. RESULTS: Here we present
      the System Biology Format Converter (SBFC), which provide a generic framework to
      potentially convert any format into another. The framework currently includes
      several converters translating between the following formats: SBML, BioPAX, SBGN
      ML, Matlab, Octave, XPP, GPML, Dot, MDL and APM. This software is written in Java
      and can be used as a standalone executable or web service. CONCLUSIONS: The SBFC
      framework is an evolving software project. Existing converters can be used and
      improved, and new converters can be easily added, making SBFC useful to both
      modellers and developers. The source code and documentation of the framework are
      freely available from the project web site.

PMID- 27044655
TI  - Environmental unpredictability and inbreeding depression select for mixed
      dispersal syndromes.
AB  - BACKGROUND: Mixed dispersal syndromes have historically been regarded as a bet
      hedging mechanism that enhances survivorship in unpredictable environments,
      ensuring that some propagules stay in the maternal environment while others can
      potentially colonize new sites. However, this entails paying the costs of both
      dispersal and non-dispersal. Propagules that disperse are likely to encounter
      unfavorable conditions, while non-dispersing propagules might form inbred
      populations of close relatives. Here, we investigate the conditions under which
      mixed dispersal syndromes emerge and are evolutionarily stable, taking into
      account the risks of both environmental unpredictability and inbreeding. RESULTS:
      Using mathematical and computational modeling, we show that high dispersal
      propensity is favored whenever environmental unpredictability is low and
      inbreeding depression high, whereas mixed dispersal syndromes are adaptive under
      high environmental unpredictability, more particularly if inbreeding depression
      is small. Although pure dispersal is frequently adaptive, mixed dispersal
      represents the optimal strategy under many different parameterizations of our
      models, indicating that this strategy is likely to be favored in a wide variety
      of contexts. Furthermore, monomorphic populations go inevitably extinct when
      environmental and genetic costs are high, whilst mixed strategies can maintain
      viable populations even under very extreme conditions. CONCLUSIONS: Our models
      support the hypothesis that the interplay between inbreeding depression and
      environmental unpredictability shapes dispersal syndromes, often resulting in
      mixed strategies. Moreover, mixed dispersal seems to facilitate persistence
      whenever conditions are critical or nearly critical for survival.

PMID- 27044656
TI  - Effect of Cardiac Resynchronisation Therapy on Electrical Remodelling.
AB  - BACKGROUND: Cardiac resynchronisation therapy (CRT) is an accepted device therapy
      in patients with low ejection fraction. Beneficial effects of CRT result from
      mechanical remodelling. Some controversial reports suggest that CRT may also
      induce electrical remodelling with intrinsic QRS narrowing but still the effect
      of CRT on electrical remodelling is an issue for debate. The aim of our study was
      to evaluate the effects of CRT on intrinsic QRS duration. For clarity, our
      analysis was performed by the signal averaged electrocardiogram (SAECG) which is
      a high resolution electrocardiographic signal suitable for accurate measurement
      of QRS duration. Signal averaged electrocardiogram provides a better value of QRS
      duration compared to 12-lead ECG by the ability to detect ventricular late
      potentials. METHODS: A total of 48 consecutive patients with severe systolic
      dysfunction and typical left bundle branch block (LBBB) were enrolled in the
      study prospectively. Patients were scheduled for CRT-D implantation according to
      the current guidelines. Intrinsic QRS duration was accurately measured by SAECG
      before and at least 14 months after CRT implantation. RESULTS: The mean intrinsic
      QRS duration remained unchanged during follow-up (from 149.9+/-13.8ms to 149.6+/
      18.4ms; P= 0.3). Among 32 CRT responder patients, the mean intrinsic QRS duration
      remained unchanged during follow-up. Also, the mean intrinsic QRS duration showed
      no significant changes in 16 CRT non-responders. CONCLUSION: Structural
      remodelling induced by CRT does not necessarily translate into decrease of
      intrinsic ventricular activation. Despite significant left ventricular recovery,
      electrical characteristics of the left ventricular conduction system cannot
      generally be expected to recuperate.

PMID- 27044657
TI  - Electrocardiographic Eligibility for Subcutaneous Implantable Cardioverter
      Defibrillator: Evaluation during Bicycle Exercise.
AB  - BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is
      used in patients at risk of sudden death. Our aim was to assess clinical
      predictors of electrocardiographic ineligibility for S-ICD, and the impact of
      exercise on S-ICD eligibility in an unselected series of patients requiring ICD
      therapy. METHODS: 102 patients at risk of sudden death were evaluated at rest and
      during exercise. Electrocardiograph screening using limb lead electrodes (to
      simulate the S-ICD sensing vectors) was performed at rest and during bicycle
      ergometer exercise. RESULTS: R wave amplitude in lead D3 during exercise >16mV,
      baseline QTc and the sum of amplitudes of the R waves at supine >30mV were
      predictors of ineligibility for S-ICD. Eligibility increased from 90% to 100% of
      patients when evaluated with an "any of the three leads" criterion compared to
      current recommendations. A more restrictive criterion based on two of three ECG
      leads caused an eligibility drop at 66%, that further decreased to 56% during
      exercise; these figures improved to 79% and 81%, respectively, when an "any 2 of
      3 leads" criterion was used. CONCLUSIONS: Huge ECG amplitude and QTc duration are
      associated with ineligibility in the current S-ICD release. By performing
      exercise testing, lead suitability changes in one patient out of 14 (7% of tested
      patients) and eligibility is decreased by use of a more stringent criterion for
      eligibility (ECG criteria satisfied in two of three leads). A dynamic selection
      of sensing vectors aiming at situation-specific suitability (any of three leads)
      would increase S-ICD eligibility to 100% of patients.

PMID- 27044658
TI  - Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and
      foam cell formation.
AB  - Many types of apoptotic cells are phagocytosed and digested by macrophages.
      Adipocytes can be hundreds of times larger than macrophages, so they are too
      large to be digested by conventional phagocytic processes. The nature of the
      interaction between macrophages and apoptotic adipocytes has not been studied in
      detail. We describe a cellular process, termed exophagy, that is important for
      macrophage clearance of dead adipocytes and adipose tissue homeostasis. Using
      mouse models of obesity, human tissue, and a cell culture model, we show that
      macrophages form hydrolytic extracellular compartments at points of contact with
      dead adipocytes using local actin polymerization. These compartments are acidic
      and contain lysosomal enzymes delivered by exocytosis. Uptake and complete
      degradation of adipocyte fragments, which are released by extracellular
      hydrolysis, leads to macrophage foam cell formation. Exophagy-mediated foam cell
      formation is a highly efficient means by which macrophages internalize large
      amounts of lipid, which may ultimately overwhelm the metabolic capacity of the
      macrophage. This process provides a mechanism for degradation of objects, such as
      dead adipocytes, that are too large to be phagocytosed by macrophages.

PMID- 27044659
TI  - Prohibitin regulates the FSH signaling pathway in rat granulosa cell
      differentiation.
AB  - Published results from our laboratory identified prohibitin (PHB), a gene product
      expressed in granulosa cells (GCs) that progressively increases during follicle
      maturation. Our current in vitro studies demonstrate that follicle-stimulating
      hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent
      expression of PHB was primarily localized within mitochondria, and positively
      correlates with the morphological changes in GCs organelles, and synthesis and
      secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB
      plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown
      studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated
      RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression
      of the key steroidogenic enzymes including steroidogenic acute regulatory protein
      (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3beta
      hydroxysteroid dehydrogenase (3beta-HSD), and aromatase (Cyp19a1); and decreased
      E2 and P4 synthesis and secretions in the presence of FSH stimulation.
      Furthermore, these experimental studies also provided direct evidence that PHB
      within the mitochondrial fraction in GCs is phosphorylated at residues Y249,
      T258, and Y259 in response to FSH stimulation. The observed levels of
      phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in
      the absence of FSH stimulation. In addition, during GC differentiation FSH
      induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2
      signaling pathway. Taken together, these studies provide new evidence supporting
      FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the
      differentiated state of GCs.

PMID- 27044660
TI  - Glucose control of glucagon secretion-'There's a brand-new gimmick every year'.
AB  - Glucagon from the pancreatic alpha-cells is a major blood glucose-regulating
      hormone whose most important role is to prevent hypoglycaemia that can be life
      threatening due to the brain's strong dependence on glucose as energy source.
      Lack of blood glucose-lowering insulin after malfunction or autoimmune
      destruction of the pancreatic beta-cells is the recognized cause of diabetes, but
      recent evidence indicates that diabetic hyperglycaemia would not develop unless
      lack of insulin was accompanied by hypersecretion of glucagon. Glucagon release
      has therefore become an increasingly important target in diabetes management.
      Despite decades of research, an understanding of how glucagon secretion is
      regulated remains elusive, and fundamentally different mechanisms continue to be
      proposed. The autonomous nervous system is an important determinant of glucagon
      release, but it is clear that secretion is also directly regulated within the
      pancreatic islets. The present review focuses on pancreatic islet mechanisms
      involved in glucose regulation of glucagon release. It will be argued that alpha
      cell-intrinsic processes are most important for regulation of glucagon release
      during recovery from hypoglycaemia and that paracrine inhibition by somatostatin
      from the delta-cells shapes pulsatile glucagon release in hyperglycaemia. The
      electrically coupled beta-cells ultimately determine islet hormone pulsatility by
      releasing synchronizing factors that affect the alpha- and delta-cells. 

PMID- 27044661
TI  - A combined surveillance program and quality register improves management of
      childhood disability.
AB  - PURPOSE: To describe a concept for prevention of secondary conditions in
      individuals with chronic neuromuscular disabilities by using two Swedish
      developed follow-up-programmes for cerebral palsy (CP; CPUP) and myelomeningocele
      (MMC; MMCUP) respectively as examples. METHOD: This paper describes and outlines
      the rationale, development and implementation of CPUP and MMCUP. RESULTS: Both
      programmes are multidisciplinary longitudinal follow-up programmes that
      simultaneously serve as national registries. The programmes are population-based
      and set in Swedish habilitation clinics. Most children (95%) born 2000 or later
      with CP are enrolled in CPUP and the recruitment of adults is underway. CPUP has
      also been implemented in Norway, Denmark, Iceland, Scotland and parts of
      Australia. In MMCUP, almost all children with MMC born 2007 or later participate
      and individuals of all ages are now invited. The registries provide
      epidemiological profiles associated with CP and MMC and platforms for population
      based research and quality of care improvement. CONCLUSIONS: Through
      multidisciplinary follow-up and early detection of emerging complications
      individuals with CP or MMC can receive less complex and more effective
      interventions than if treatment is implemented at a later stage. Possibilities
      and challenges to design, implement and continuously run multidisciplinary
      secondary prevention follow-up programmes and quality registries for individuals
      with CP or MMC are described and discussed. Implications for rehabilitation
      Individuals with disabilities such as cerebral palsy or myelomeningocele are at
      risk of developing secondary conditions. Multidisciplinary population-based
      longitudinal follow-up programmes seem effective in preventing certain types of
      secondary conditions.

PMID- 27044662
TI  - Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating
      neural stem cell fate are mediated via endocannabinoid signalling pathways.
AB  - Emerging evidence suggests a complex interplay between the endocannabinoid
      system, omega-3 fatty acids and the immune system in the promotion of brain self
      repair. However, it is unknown if all omega-3 fatty acids elicit similar effects
      on adult neurogenesis and if such effects are mediated or regulated by
      interactions with the endocannabinoid system. This study investigated the effects
      of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid
      signalling pathways in these effects. EPA, but not DHA, significantly increased
      proliferation of NSCs compared to controls, an effect associated with enhanced
      levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK,
      effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor
      antagonists. Furthermore, in NSCs derived from IL-1beta deficient mice, EPA
      significantly decreased proliferation and p-p38 MAPK levels compared to controls,
      suggesting a key role for IL-1beta signalling in the effects observed. Although
      DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant
      increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL
      1beta deficient mice, DHA significantly increased proliferation without effects
      on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling
      pathways. These results provide crucial new insights into the divergent effects
      of EPA and DHA in regulating NSC proliferation and the pathways involved, and
      highlight the therapeutic potential of their interplay with endocannabinoid
      signalling in brain repair.

PMID- 27044663
TI  - Activity dependent internalization of the glutamate transporter GLT-1 mediated by
      beta-arrestin 1 and ubiquitination.
AB  - GLT-1 is the main glutamate transporter in the brain and undergoes trafficking
      processes that control its concentration on the cell surface thereby shaping
      glutamatergic neurotransmission. We have investigated how the traffic of GLT-1 is
      regulated by transporter activity. We report that internalization of GLT-1 from
      the cell surface is accelerated by transportable substrates like glutamate or
      aspartate, as well as by the transportable inhibitor L-trans-2,4-PDC, but not by
      the non-substrate inhibitor WAY 213613 in primary mixed cultures and in
      transiently transfected HEK293 cells. Analysis of the mechanism of endocytosis in
      HEK293 cells revealed that glutamate promoted the association with the
      transporter of the adaptor protein beta-arrestin and the ubiquitin ligase Nedd4
      2. The addition of glutamate is accompanied by an increase in the transporter
      ubiquitination, and the internalization is suppressed by an ubiquitination
      inhibitor (PYR41), and in a mutant defective in C-terminal lysines. The glutamate
      triggered endocytosis was also suppressed by siRNA for beta-arrestin. This
      regulatory mechanism might be relevant in controlling the amount of transporter
      on the cell surface in conditions such as ischemia or traumatic brain injury,
      where extracellular concentrations of glutamate are persistently elevated.

PMID- 27044664
TI  - Neuropeptide S reduces fear and avoidance of con-specifics induced by social fear
      conditioning and social defeat, respectively.
AB  - Neuropeptide S (NPS) has anxiolytic effects and facilitates extinction of cued
      fear in rodents. Here, we investigated whether NPS reverses social fear and
      social avoidance induced by social fear conditioning (SFC) and acute social
      defeat (SD), respectively, in male CD1 mice. Our results revealed that
      intracerebroventricular NPS (icv; 10 and 50 nmol/2 MUl) reversed fear of unknown
      con-specifics induced by SFC and dose-dependently reduced avoidance of known
      aggressive con-specifics induced by SD. While 50 nmol of NPS completely reversed
      social avoidance and reinstated social preference, 10 nmol of NPS reduced social
      avoidance, but did not completely reinstate social preference in socially
      defeated mice. Further, a lower dose (1 nmol/2 MUl) of NPS facilitated the within
      session extinction of cued fear, while a higher dose (10 nmol/2 MUl) reduced the
      expression of cued fear. We could also confirm the anxiolytic effects of NPS (1,
      10 and 50 nmol/2 MUl) on the elevated plus-maze (EPM), which were not accompanied
      by alterations in locomotor activity either on the EPM or in the home cage.
      Finally, we could show that icv infusion of the NPS receptor 1 antagonist D
      Cys((t)Bu)(5)-NPS (10 nmol/2 MUl) did not alter SFC-induced social fear, general
      anxiety and locomotor activity. Taken together, our study extends the potent
      anxiolytic profile of NPS to a social context by demonstrating the reduction of
      social fear and social avoidance, thus providing the framework for studies
      investigating the involvement of the NPS system in the regulation of different
      types of social behaviour.

PMID- 27044665
TI  - The Potential Effects of Obesity on Social Security Claiming Behavior and
      Retirement Benefits.
AB  - Objectives: Obesity prevalence among Americans has increased for nearly three
      decades. We explore the relationship between the rise in obesity and Social
      Security retirement benefit claiming, a decision impacting nearly all aging
      Americans. Specifically, we investigate whether obesity can affect individuals'
      decision to claim benefits early, a choice that has important implications for
      financial security in retirement, particularly for those with lower socioeconomic
      status (SES). Method: We use a microsimulation model called MINT6 (Modeling
      Income in the Near Term, version 6) to demonstrate the potential effects of
      obesity on subjective life expectancy and claiming behavior. We impute obesity
      status using data from the National Health and Nutrition Examination Survey
      (NHANES), which describes the distribution of obesity prevalence within the
      United States by gender, poverty status, and race/ethnicity. Results: We find
      that the rise in obesity and the consequent incidence of obesity-related diseases
      may lead some individuals to make claiming decisions that lead to lower monthly
      and lifetime Social Security retirement benefits. Further, we find that the
      potential economic impact of this decision is larger for those with lower SES.
      Discussion: We present a behavioral perspective by addressing the potential
      effects that obesity can have on individuals' retirement decisions and their
      resulting Social Security retirement benefits.

PMID- 27044666
TI  - Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase
      Function but Not for the Renin-Angiotensin System.
AB  - ATPase H+-transporting lysosomal accessory protein 2 (Atp6ap2), also known as the
      (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit
      of the vacuolar H+-ATPase (V-ATPase) that may also function within the renin
      angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin
      dependent functions remains unconfirmed. Using mice with an inducible conditional
      deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V
      ATPase expression and activity in the intercalated cells of the collecting duct
      impaired acid-base regulation by the kidney. In addition, these mice suffered
      from marked polyuria resistant to desmopressin administration. Immunoblotting
      revealed downregulation of the medullary Na+-K+-2Cl- cotransporter NKCC2 in these
      mice compared with wild-type mice, an effect accompanied by a hypotonic medullary
      interstitium and impaired countercurrent multiplication. This phenotype
      correlated with strong autophagic defects in epithelial cells of medullary
      tubules. Notably, cells with high accumulation of the autophagosomal substrate
      p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron
      specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin
      II-dependent BP regulation, or sodium handling in the kidney. Taken together, our
      results show that nephron-specific deletion of Atp6ap2 does not affect the renin
      angiotensin system but causes a combination of renal concentration defects and
      distal renal tubular acidosis as a result of impaired V-ATPase activity.

PMID- 27044667
TI  - Relation between injury of the hypothalamus and subjective excessive daytime
      sleepiness in patients with mild traumatic brain injury.

PMID- 27044668
TI  - Prevalence and Costs of Five Chronic Conditions in Children.
AB  - The objective is to examine the prevalence and health-care costs associated with
      asthma, epilepsy, hypertension, food allergies, and diabetes in children aged 0
      18 years. Prevalence was calculated using 2005-2012 Medical Expenditure Panel
      Survey (MEPS) data, a population-based, nationally representative sample. Using
      MEPS, two-part models estimated the cost of each condition for all children while
      controlling for sociodemographic categories. Prevalence rates varied by race and
      ethnicity across conditions. Females had higher prevalence of all chronic
      conditions, except epilepsy. An additional US$1,377.60-US$9,059.49 annually were
      spent on medical expenses for children aged 0-18 years, with asthma, diabetes, or
      epilepsy compared to children without these conditions. This is the first study
      to examine the costs and prevalence of chronic health conditions in children and
      adolescents using a single data set. Understanding the odds of having a condition
      by sociodemographic categories highlights disparities that can potentially inform
      school nurses on the best allocation of resources to serve students. 

PMID- 27044669
TI  - Barriers to Asthma Management as Identified by School Nurses.
AB  - Asthma rates are increasing in children. School nurses have opportunities to care
      for children with asthma but need to overcome barriers impacting their ability to
      manage asthma in the school setting. This study (a) assessed barriers present in
      the school setting, (b) determined the impact of barriers on performance of
      asthma management behaviors, and (c) determined the impact of barriers on
      importance ratings of asthma management behaviors, asthma self-efficacy, and
      asthma attitudes (N = 537). Results revealed 72% of the nurses reported at least
      one barrier. As numbers of barriers increased, performance of asthma management
      behaviors decreased. Significant relationships were found between specific asthma
      management behaviors and specific barriers. No significant relationships were
      found between barriers and asthma self-efficacy, asthma attitude, or importance
      ratings of asthma management behaviors. Removing barriers may allow the nurse to
      perform at greatest effectiveness, enhancing the positive outcomes that result
      from appropriate asthma management. 

PMID- 27044670
TI  - Structural, electronic, and magnetic properties of tris(8
      hydroxyquinoline)iron(III) molecules and their magnetic coupling with
      ferromagnetic surface: first-principles study.
AB  - Using first-principles calculations, we have systematically investigated the
      structural, electronic, and magnetic properties of facial (fac-) and meridional
      (mer-) tris(8-hydroxyquinoline)iron(III) (Feq3) molecules and their interaction
      with ferromagnetic substrate. Our calculation results show that for the isolated
      Feq3, mer-Feq3 is more stable than the fac-Feq3; both Feq3 isomers have a high
      spin-state of 5 MUB as the ground state when an on-site Hubbard-U term is
      included to treat the highly localized Fe 3d electrons; while the standard DFT
      calculations produce a low spin-state of 1 MUB for mer-Feq3. These magnetic
      behaviors can be understood by the octahedral ligand field splitting theory.
      Furthermore, we found that fac-Feq3 has a stronger bonding to the Co surface than
      mer-Feq3 and an anti-ferromagnetic coupling was discovered between Fe and Co
      substrate, originating from the superexchange coupling between Fe and Co mediated
      by the interface oxygen and nitrogen atoms. These findings suggest that Feq3
      molecular films may serve as a promising spin-filter material in spintronic
      devices.

PMID- 27044671
TI  - A SAL1 Loss-of-Function Arabidopsis Mutant Exhibits Enhanced Cadmium Tolerance in
      Association with Alleviation of Endoplasmic Reticulum Stress.
AB  - SAL1, as a negative regulator of stress response signaling, has been studied
      extensively for its role in plant response to environmental stresses. However,
      the role of SAL1 in cadmium (Cd) stress response and the underlying mechanism is
      still unclear. Using an Arabidopsis thaliana loss-of-function mutant of SAL1, we
      assessed Cd resistance and further explored the Cd toxicity mechanism through
      analysis of the endoplasmic reticulum (ER) stress response. The loss of SAL1
      function greatly improved Cd tolerance and significantly attenuated ER stress in
      Arabidopsis. Exposure to Cd induced an ER stress response in Arabidopsis as
      evidenced by unconventional splicing of AtbZIP60 and up-regulation of ER stress
      responsive genes. Damage caused by Cd was markedly reduced in the ER stress
      response double mutant bzip28 bzip60 or by application of the ER stress
      alleviating chemical agents, tauroursodeoxycholic acid (TUDCA) and 4-phenyl
      butyric acid (4-PBA), in wild-type plants. The Cd-induced ER stress in
      Arabidopsis was also alleviated by loss of function of SAL1. These results
      identified SAL1 as a new component mediating Cd toxicity and established the role
      of the ER stress response in Cd toxicity. Additionally, the attenuated ER stress
      in the sal1 mutant might also shed new light on the mechanism of diverse abiotic
      stress resistance in the SAL1 loss-of-function mutants. 

PMID- 27044672
TI  - Abscisic Acid Participates in the Control of Cell Cycle Initiation Through Heme
      Homeostasis in the Unicellular Red Alga Cyanidioschyzon merolae.
AB  - ABA is a phytohormone that is synthesized in response to abiotic stresses and
      other environmental changes, inducing various physiological responses. While ABA
      has been found in unicellular photosynthetic organisms, such as cyanobacteria and
      eukaryotic algae, its function in these organisms is poorly understood. Here, we
      found that ABA accumulated in the unicellular red alga Cyanidioschyzon merolae
      under conditions of salt stress and that the cell cycle G1/S transition was
      inhibited when ABA was added to the culture medium. A gene encoding heme
      scavenging tryptophan-rich sensory protein-related protein (CmTSPO; CMS231C) was
      positively regulated by ABA, as in Arabidopsis, and CmTSPO bound heme in vitro.
      The intracellular content of total heme was increased by addition of ABA, but
      unfettered heme decreased, presumably due to scavenging by CmTSPO. The inhibition
      of DNA replication by ABA was negated by addition of heme to the culture medium.
      Thus, we propose a regulatory role for ABA and heme in algal cell cycle
      initiation. Finally, we found that a C. merolae mutant that is defective in ABA
      production was more susceptible to salt stress, indicating the importance of ABA
      to stress resistance in red algae. 

PMID- 27044675
TI  - Parametric excitation and squeezing in a many-body spinor condensate.
AB  - Atomic spins are usually manipulated using radio frequency or microwave fields to
      excite Rabi oscillations between different spin states. These are single-particle
      quantum control techniques that perform ideally with individual particles or non
      interacting ensembles. In many-body systems, inter-particle interactions are
      unavoidable; however, interactions can be used to realize new control schemes
      unique to interacting systems. Here we demonstrate a many-body control scheme to
      coherently excite and control the quantum spin states of an atomic Bose gas that
      realizes parametric excitation of many-body collective spin states by time
      varying the relative strength of the Zeeman and spin-dependent collisional
      interaction energies at multiples of the natural frequency of the system.
      Although parametric excitation of a classical system is ineffective from the
      ground state, we show that in our experiment, parametric excitation from the
      quantum ground state leads to the generation of quantum squeezed states. 

PMID- 27044676
TI  - Protein Repeats from First Principles.
AB  - Some natural proteins display recurrent structural patterns. Despite being highly
      similar at the tertiary structure level, repeating patterns within a single
      repeat protein can be extremely variable at the sequence level. We use a
      mathematical definition of a repetition and investigate the occurrences of these
      in sequences of different protein families. We found that long stretches of
      perfect repetitions are infrequent in individual natural proteins, even for those
      which are known to fold into structures of recurrent structural motifs. We found
      that natural repeat proteins are indeed repetitive in their families, exhibiting
      abundant stretches of 6 amino acids or longer that are perfect repetitions in the
      reference family. We provide a systematic quantification for this repetitiveness.
      We show that this form of repetitiveness is not exclusive of repeat proteins, but
      also occurs in globular domains. A by-product of this work is a fast
      quantification of the likelihood of a protein to belong to a family. 

PMID- 27044677
TI  - Glass polymorphism in glycerol-water mixtures: II. Experimental studies.
AB  - We report a detailed experimental study of (i) pressure-induced transformations
      in glycerol-water mixtures at T = 77 K and P = 0-1.8 GPa, and (ii) heating
      induced transformations of glycerol-water mixtures recovered at 1 atm and T = 77
      K. Our samples are prepared by cooling the solutions at ambient pressure at
      various cooling rates (100 K s(-1)-10 K h(-1)) and for the whole range of
      glycerol mole fractions, chi(g). Depending on concentration and cooling rates,
      cooling leads to samples containing amorphous ice (chig >= 0.20), ice (chi(g) <=
      0.32), and/or "distorted ice" (0 < chi(g) <= 0.38). Upon compression, we find
      that (a) fully vitrified samples at chi(g) >= 0.20 do not show glass
      polymorphism, in agreement with previous works; (b) samples containing ice show
      pressure-induced amorphization (PIA) leading to the formation of high-density
      amorphous ice (HDA). PIA of ice domains within the glycerol-water mixtures is
      shown to be possible only up to chi(g) ~ 0.32 (T = 77 K). This is rather
      surprising since it has been known that at chi(g) < 0.38, cooling leads to phase
      separated samples with ice and maximally freeze-concentrated solution of chi(g) ~
      0.38. Accordingly, in the range 0.32 < chi(g) < 0.38, we suggest that the water
      domains freeze into an interfacial ice, i.e., a highly-distorted form of layered
      ice, which is unable to transform to HDA upon compression. Upon heating samples
      recovered at 1 atm, we observe a rich phase behavior. Differential scanning
      calorimetry indicates that only at chi(g) <= 0.15, the water domains within the
      sample exhibit polyamorphism, i.e., the HDA-to-LDA (low-density amorphous ice)
      transformation. At 0.15 < chi(g) <= 0.38, samples contain ice, interfacial ice,
      and/or HDA domains. All samples (chi(g) <= 0.38) show: the crystallization of
      amorphous ice domains, followed by the glass transition of the vitrified glycerol
      water domains and, finally, the melting of ice at high temperatures. Our work
      exemplifies the complex "phase" behavior of glassy binary mixtures due to phase
      separation (ice formation) and polyamorphism, and the relevance of sample
      preparation, concentration as well as cooling rates. The presence of the
      distorted ice (called "interphase" by us) also explains the debated "drift
      anomaly" upon melting. These results are compatible with the high-pressure study
      by Suzuki and Mishima indicating disappearance of polyamorphism at P ~ 0.03-0.05
      GPa at chi(g) ~ 0.12-0.15 [J. Chem. Phys., 2014, 141, 094505].

PMID- 27044678
TI  - Transgenerational influence of sensorimotor training on offspring behavior and
      its neural basis in Drosophila.
AB  - Whether specific learning experiences by parents influence the behavior of
      subsequent generations remains unclear. This study examines whether and what
      aspects of parental sensorimotor training prior to conception affect the behavior
      of subsequent generations and identifies the neural circuitries in Drosophila
      responsible for mediating these effects. Using genetic and anatomic techniques, I
      find that both first- and second-generation offspring of parents who underwent
      prolonged olfactory training over many days displayed a weak but selective
      approach bias to the same trained odors. However, I also find that the offspring
      did not differentiate between orders based on whether parental training was
      aversive or appetitive. Disruption of both olfactory-receptor and dorsal-paired
      medial neuron input into the mushroom bodies abolished this change in offspring
      response, but disrupting synaptic output from alpha/beta neurons of the mushroom
      body themselves had little effect on behavior even though they remained necessary
      for enacting newly trained conditioned responses. This study provides a circuit
      based understanding of how specific sensory experiences in Drosophila may bias
      the behavior of subsequent generations, and identifies a transgenerational
      dissociation between the effects of conditioned and unconditioned sensory
      stimuli.

PMID- 27044679
TI  - Genetic evidence for chromosome 4 loci influencing learning and memory.
AB  - The Lewis (LEW) and SHR (Spontaneously Hypertensive Rats) inbred rat strains
      differ in several anxiety/emotionality and learning/memory-related behaviors. We
      aimed to search quantitative trait locus (QTL) that influence these behaviors and
      confirm their effects in a congenic rat strain SLA16 (SHR.LEW.Anxrr16). LEW
      females and SHR males were intercrossed to produce F2 rats (96/sex), which were
      all tested in the plus-maze discriminative avoidance task (PMDAT), open-field
      (OF), object recognition (OR), spontaneous alternation (SA) and fear conditioning
      (FC). All animals were genotyped for microsatellite markers located on chromosome
      (Chr) 4. Behavioral and genotypic data were used to perform factor and QTL
      analyses. Also, to confirm the QTL effects, we tested male and female SLA16 rats
      and their isogenic control SHR in the same behavioral tests. A factor analysis of
      the F2 population revealed a correlation between anxiety/emotionality related
      behaviors and learning/memory in both sexes. QTL analysis revealed two
      significant QTL in males and three in females, on behavioral parameters in the
      PMDAT, OF and FC. Four QTL found herein were confirmed in SLA16 rats. The SLA16
      strain displayed lower levels of anxiety/emotionality, higher locomotor activity
      and deficits in learning/memory in comparison with SHR strain. The Chr 4 contains
      genes influencing anxiety/emotionality and learning/memory behaviors and the
      SLA16 strain represents a valuable tool in the search for them. The use of the
      SLA16 strain as a genetic model for studying behavioral phenomena and their
      implications for psychiatric disorders are discussed.

PMID- 27044680
TI  - My Conscience May Be My Guide, but You May Not Need to Honor It.
AB  - A number of healthcare professionals assert a right to be exempt from performing
      some actions currently designated as part of their standard professional
      responsibilities. Most advocates claim that they should be excused from these
      duties simply by averring that they are conscientiously opposed to performing
      them. They believe that they need not explain or justify their decisions to
      anyone, nor should they suffer any undesirable consequences of such refusal.
      Those who claim this right err by blurring or conflating three issues about the
      nature and role of conscience, and its significance in determining what other
      people should permit them to do (or not do). Many who criticize those asserting
      an exemption conflate the same questions and blur the same distinctions, if not
      expressly, by failing to acknowledge that sometimes a morally serious agent
      should not do what she might otherwise be expected to do. Neither side seems to
      acknowledge that in some cases both claims are true. I identify these conflations
      and specify conditions in which a professional might reasonably refuse to do what
      she is required to do. Then I identify conditions in which the public should
      exempt a professional from some of her responsibilities. I argue that
      professionals should refuse far less often than most advocates do . . . and that
      they should be even less frequently exempt. Finally, there are compelling reasons
      why we could not implement a consistent policy giving advocates what they want,
      likely not even in qualified form.

PMID- 27044681
TI  - FCGR3A-V158F polymorphism is a disease-specific pharmacogenetic marker for the
      treatment of psoriasis with Fc-containing TNFalpha inhibitors.
AB  - Psoriasis is a multifactorial skin disease affecting ~2% of world's population,
      causing a dramatic decrease in patients' quality of life and a significant
      increase in health-care expenses. Biological agents such as the anti-TNFalpha
      ones had an enormous impact in patients' therapy; however, a significant
      proportion of them do not respond well, an outcome attributed mainly to genetic
      factors. Recently, in a large European cohort of rheumatoid arthritis patients we
      have shown association with variation in the receptors that correspond to the Fc
      portion of the biological agents. As both diseases share common immunological
      fingerprints, we examined the hypothesis that they share common pharmacogenetic
      markers. Analysis of FCGR2A-H131R and FCGR3A-V158F polymorphisms in 100 psoriasis
      patients showed association only with respect to FCGR3A-V158F and response to
      etanercept (P=0.018). Interestingly, no association was found between FCGR2A
      H131R and response to anti-TNFalpha therapy (P=0.882). This study suggests a role
      for FCGR3A-V158F polymorphism unique for psoriasis.

PMID- 27044682
TI  - A pharmacogenomic profile of human neural progenitors undergoing differentiation
      in the presence of the traditional Chinese medicine NeuroAiD.
AB  - NeuroAiD, a traditional Chinese medicine widely used to treat stroke patients in
      China, was recently demonstrated in rodent models and in clinical trials to
      possess neuroregenerative and neuroprotective properties. In order to understand
      the mechanisms employed by NeuroAiD to bring about its neuroproliferative and
      neuroprotective effects, we investigated the impact of MLC901, a reformulated
      version of MLC601, on human neural progenitors undergoing neural differentiation
      at the molecular level by performing three independent microarray experiments.
      Functional annotations of the genes regulated by MLC901 that were associated with
      neurogenesis were found to be enriched. We also identified potential targets
      (FGF19, GALR2, MMP10, FGF3 and TDO2) of MLC901 that could promote neurogenesis
      and neuroprotection in the human brain. This work highlighted some interesting
      targets and offered some insights into the possible mechanism of action of
      MLC901. The discovery could also provide a platform to the development of future
      therapeutic targets.

PMID- 27044683
TI  - Glucagon secretion from pancreatic alpha-cells.
AB  - Type 2 diabetes involves a menage a trois of impaired glucose regulation of
      pancreatic hormone release: in addition to impaired glucose-induced insulin
      secretion, the release of the hyperglycaemic hormone glucagon becomes
      dysregulated; these last-mentioned defects exacerbate the metabolic consequences
      of hypoinsulinaemia and are compounded further by hypersecretion of somatostatin
      (which inhibits both insulin and glucagon secretion). Glucagon secretion has been
      proposed to be regulated by either intrinsic or paracrine mechanisms, but their
      relative significance and the conditions under which they operate are debated.
      Importantly, the paracrine and intrinsic modes of regulation are not mutually
      exclusive; they could operate in parallel to control glucagon secretion. Here we
      have applied mathematical modelling of alpha-cell electrical activity as a novel
      means of dissecting the processes that underlie metabolic regulation of glucagon
      secretion. Our analyses indicate that basal hypersecretion of somatostatin and/or
      increased activity of somatostatin receptors may explain the loss of adequate
      counter-regulation under hypoglycaemic conditions, as well as the physiologically
      inappropriate stimulation of glucagon secretion during hyperglycaemia seen in
      diabetic patients. We therefore advocate studying the interaction of the
      paracrine and intrinsic mechanisms; unifying these processes may give a more
      complete picture of the regulation of glucagon secretion from alpha-cells than
      studying the individual parts. 

PMID- 27044684
TI  - Identification of Small-Molecule Frequent Hitters of Glutathione S-Transferase
      Glutathione Interaction.
AB  - In high-throughput screening (HTS) campaigns, the binding of glutathione S
      transferase (GST) to glutathione (GSH) is used for detection of GST-tagged
      proteins in protein-protein interactions or enzyme assays. However, many false
      positives, so-called frequent hitters (FH), arise that either prevent GST/GSH
      interaction or interfere with assay signal generation or detection. To identify
      GST-FH compounds, we analyzed the data of five independent AlphaScreen-based
      screening campaigns to classify compounds that inhibit the GST/GSH interaction.
      We identified 53 compounds affecting GST/GSH binding but not influencing His
      tag/Ni(2+)-NTA interaction and general AlphaScreen signals. The structures of
      these 53 experimentally identified GST-FHs were analyzed in chemoinformatic
      studies to categorize substructural features that promote interference with
      GST/GSH binding. Here, we confirmed several existing chemoinformatic filters and
      more importantly extended them as well as added novel filters that specify
      compounds with anti-GST/GSH activity. Selected compounds were also tested using
      different antibody-based GST detection technologies and exhibited no interference
      clearly demonstrating specificity toward their GST/GSH interaction. Thus, these
      newly described GST-FH will further contribute to the identification of FH
      compounds containing promiscuous substructures. The developed filters were
      uploaded to the OCHEM website (http://ochem.eu) and are publicly accessible for
      analysis of future HTS results. 

PMID- 27044685
TI  - A Multiplexed High-Content Screening Approach Using the Chromobody Technology to
      Identify Cell Cycle Modulators in Living Cells.
AB  - Many screening hits show relatively poor quality regarding later efficacy and
      safety. Therefore, small-molecule screening efforts shift toward high-content
      analysis providing more detailed information. Here, we describe a novel screening
      approach to identify cell cycle modulators with low toxicity by combining the
      Cell Cycle Chromobody (CCC) technology with the CytoTox-Glo (CTG) cytotoxicity
      assay. The CCC technology employs intracellularly functional single-domain
      antibodies coupled to a fluorescent protein (chromobodies) to visualize the cell
      cycle-dependent redistribution of the proliferating cell nuclear antigen (PCNA)
      in living cells. This image-based cell cycle analysis was combined with
      determination of dead-cell protease activity in cell culture supernatants by the
      CTG assay. We adopted this multiplex approach to high-throughput format and
      screened 960 Food and Drug Administration (FDA)-approved drugs. By this, we
      identified nontoxic compounds, which modulate different cell cycle stages, and
      validated selected hits in diverse cell lines stably expressing CCC.
      Additionally, we independently validated these hits by flow cytometry as the
      current state-of-the-art format for cell cycle analysis. This study demonstrates
      that CCC imaging is a versatile high-content screening approach to identify cell
      cycle modulators, which can be multiplexed with cytotoxicity assays for early
      elimination of toxic compounds during screening. 

PMID- 27044686
TI  - Child Poverty in the United States Today: Introduction and Executive Summary.

PMID- 27044687
TI  - Home Visiting: A Service Strategy to Reduce Poverty and Mitigate Its
      Consequences.
AB  - Home visiting programs are increasingly recognized as an important part of the
      early childhood system of care in the United States. The objectives of this
      report are to review the rationale for home visiting; characterize the Federal
      Home Visiting Program; highlight the evidence of home visiting effectiveness,
      particularly for low income families; identify opportunities to promote
      coordination between medical homes and home visiting programs; and explain the
      critical role of research, evaluation, and quality improvement to strengthen home
      visiting effectiveness. Home visiting programs offer voluntary home-based
      services and other supports to meet the needs of vulnerable pregnant women and
      young families. Home visiting intends to address poverty in 2 ways. First, it
      promotes economic self-sufficiency directly by building parents' knowledge,
      skills, and motivation related to employment opportunities and by linking
      families with community services such as adult education and job training.
      Second, it mitigates the effects of poverty through direct service and community
      linkages to enhance parents' capacity for positive parenting and for their own
      health and family functioning. Home visiting has shown effectiveness in multiple
      domains, including family economic self-sufficiency, birth outcomes, maternal
      health, child health and development, and positive parenting practices.
      Authorized as part of the Affordable Care Act in 2010 and reauthorized in 2015,
      the Federal Home Visiting Program invests an unprecedented $1.9 billion in the
      form of grants to states to expand home visiting programs and support rigorous
      research. As part of the early childhood system of services, home visiting
      programs must coordinate with other community services and supports. Programs
      will be most effective when resources are used efficiently, duplication of
      services is avoided, and alignment and reinforcement of other providers' messages
      are achieved. The Federal Home Visiting Program has established 4 mechanisms of
      research, evaluation, and quality improvement to enhance home visiting
      implementation and effectiveness. 

PMID- 27044688
TI  - Mitigating the Effects of Family Poverty on Early Child Development through
      Parenting Interventions in Primary Care.
AB  - Poverty related disparities in early child development and school readiness are a
      major public health crisis, the prevention of which has emerged in recent years
      as a national priority. Interventions targeting parenting and the quality of the
      early home language environment are at the forefront of efforts to address these
      disparities. In this article we discuss the innovative use of the pediatric
      primary care platform as part of a comprehensive public health strategy to
      prevent adverse child development outcomes through the promotion of parenting.
      Models of interventions in the pediatric primary care setting are discussed with
      evidence of effectiveness reviewed. Taken together, a review of this significant
      body of work shows the tremendous potential to deliver evidence-based preventive
      interventions to families at risk for poverty related disparities in child
      development and school readiness at the time of pediatric primary care visits. We
      also addresss considerations related to scaling and maximizing the effect of
      pediatric primary care parenting interventions and provide key policy
      recommendations.

PMID- 27044689
TI  - Reforming Preschools and Schools.
AB  - Compared with their higher-income counterparts, children growing up in low-income
      families in the United States typically complete less schooling, report worse
      health, and work and earn less in adulthood. Moreover, changes in the American
      economy over the last 40 years have raised the level of skills and qualifications
      that children need to obtain a good middle-class job, as well as making it much
      more difficult for children from low-income families to attend schools that
      support their learning of these skills. We first review strategies used in the
      past to improve K-12 schooling-including investing more money, introducing more
      accountability, and putting in place new governance structures (eg, charter
      schools)-and show why these strategies have been relatively ineffective. Drawing
      on the research literature and case studies, we then describe education reform
      strategies for prekindergarten programs and for elementary, middle, and high
      schools that may help meet these challenges. All of the initiatives described in
      our case studies provide ample opportunities for teachers and school leaders to
      improve their skills through coaching and other professional development
      activities; incorporate sensible systems of accountability, including requiring
      teachers to open their classrooms to the scrutiny of colleagues and school
      leaders and to work with their colleagues to improve their teaching practices;
      and incorporate high academic standards, such as those described in the Common
      Core State Standards. By focusing directly on improving teaching and promoting
      learning, these successful initiatives have boosted the achievement of low-income
      children. They show that it is indeed possible to make a real difference in the
      life chances of low-income children.

PMID- 27044690
TI  - Neighborhood-Level Interventions to Improve Childhood Opportunity and Lift
      Children Out of Poverty.
AB  - Population health is associated with the socioeconomic characteristics of
      neighborhoods. There is considerable scientific and policy interest in community
      level interventions to alleviate child poverty. Intergenerational poverty is
      associated with inequitable access to opportunities. Improving opportunity
      structures within neighborhoods may contribute to improved child health and
      development. Neighborhood-level efforts to alleviate poverty for all children
      require alignment of cross-sector efforts, community engagement, and
      multifactorial approaches that consider the role of people as well as place. We
      highlight several accessible tools and strategies that health practitioners can
      engage to improve regional and local systems that influence child opportunity.
      The Child Opportunity Index is a population-level surveillance tool to describe
      community-level resources and inequities in US metropolitan areas. The case
      studies reviewed outline strategies for creating higher opportunity neighborhoods
      for pediatricians interested in working across sectors to address the impact of
      neighborhood opportunity on child health and well-being.

PMID- 27044691
TI  - How Can We Reduce Child Poverty and Support Parental Employment?

PMID- 27044692
TI  - Redesigning Health Care Practices to Address Childhood Poverty.
AB  - Child poverty in the United States is widespread and has serious negative effects
      on the health and well-being of children throughout their life course. Child
      health providers are considering ways to redesign their practices in order to
      mitigate the negative effects of poverty on children and support the efforts of
      families to lift themselves out of poverty. To do so, practices need to adopt
      effective methods to identify poverty-related social determinants of health and
      provide effective interventions to address them. Identification of needs can be
      accomplished with a variety of established screening tools. Interventions may
      include resource directories, best maintained in collaboration with
      local/regional public health, community, and/or professional organizations;
      programs embedded in the practice (eg, Reach Out and Read, Healthy Steps for
      Young Children, Medical-Legal Partnership, Health Leads); and collaboration with
      home visiting programs. Changes to health care financing are needed to support
      the delivery of these enhanced services, and active advocacy by child health
      providers continues to be important in effecting change. We highlight the ongoing
      work of the Health Care Delivery Subcommittee of the Academic Pediatric
      Association Task Force on Child Poverty in defining the ways in which child
      health care practice can be adapted to improve the approach to addressing child
      poverty. 

PMID- 27044693
TI  - An Essential Role for Pediatricians: Becoming Child Poverty Change Agents for a
      Lifetime.
AB  - Poverty has profound and enduring effects on the health and well-being of
      children, as well as their subsequent adult health and success. It is essential
      for pediatricians to work to reduce child poverty and to ameliorate its effects
      on children. Pediatricians have important and needed tools to do this work:
      authority/power as physicians, understanding of science and evidence-based
      approaches, and first-hand, real-life knowledge and love of children and
      families. These tools need to be applied in partnership with community-based
      organizations/leaders, educators, human service providers, business leaders,
      philanthropists, and policymakers. Examples of the effects of pediatricians on
      the issue of child poverty are seen in Ferguson, Missouri; Denver, Colorado; and
      Rochester, New York. In addition, national models exist such as the American
      Academy of Pediatrics Community Pediatrics Training Initiative, which engages
      numerous pediatric faculty to learn and work together to make changes for
      children and families who live in poverty and to teach these skills to pediatric
      trainees. Some key themes/lessons for a pediatrician working to make changes in a
      community are to bear witness to and recognize injustice for children and
      families; identify an area of passion; review the evidence and gain expertise on
      the issue; build relationships and partnerships with community leaders and
      organizations; and advocate for effective solutions.

PMID- 27044694
TI  - Childhood Poverty and Its Effect on Health and Well-being: Enhancing Training for
      Learners Across the Medical Education Continuum.
AB  - OBJECTIVE: Childhood poverty is unacceptably common in the US and threatens the
      health, development, and lifelong well-being of millions of children. Health care
      providers should be prepared through medical curricula to directly address the
      health harms of poverty. In this article, authors from The Child Poverty
      Education Subcommittee (CPES) of the Academic Pediatric Association Task Force on
      Child Poverty describe the development of the first such child poverty curriculum
      for teachers and learners across the medical education continuum. METHODS:
      Educators, physicians, trainees, and public health professionals from 25
      institutions across the United States and Canada were convened over a 2-year
      period and addressed 3 goals: 1) define the core competencies of child poverty
      education, 2) delineate the scope and aims of a child poverty curriculum, and 3)
      create a child poverty curriculum ready to implement in undergraduate and
      graduate medical education settings. RESULTS: The CPES identified 4 core domains
      for the curriculum including the epidemiology of child poverty, poverty-related
      social determinants of health, pathophysiology of the health effects of poverty,
      and leadership and action to reduce and prevent poverty's health effects.
      Workgroups, focused on each domain, developed learning goals and objectives,
      built interactive learning modules to meet them, and created evaluation and
      faculty development materials to supplement the core curriculum. An editorial
      team with representatives from each workgroup coordinated activities and are
      preparing the final curriculum for national implementation. CONCLUSIONS: This
      comprehensive, standardized child poverty curriculum developed by an
      international group of educators in pediatrics and experts in the health effects
      of poverty should prepare medical trainees to address child poverty and improve
      the health of poor children.

PMID- 27044695
TI  - Poverty, Complexity, and a New Way Forward.

PMID- 27044696
TI  - The Work for Our Generation: Reimagining Communities of Opportunities for All.

PMID- 27044697
TI  - The Cost of Poverty and the Value of Hope.

PMID- 27044698
TI  - Poverty is Not Just an Indicator: The Relationship Between Income, Poverty, and
      Child Well-Being.
AB  - In this article, we review the evidence on the effects of poverty and low income
      on children's development and well-being. We argue that poverty is an important
      indicator of societal and child well-being, but that poverty is more than just an
      indicator. Poverty and low income are causally related to worse child development
      outcomes, particularly cognitive developmental and educational outcomes.
      Mechanisms through which poverty affects these outcomes include material
      hardship, family stress, parental and cognitive inputs, and the developmental
      context to which children are exposed. The timing, duration, and community
      context of poverty also appear to matter for children's outcomes-with early
      experiences of poverty, longer durations of poverty, and higher concentrations of
      poverty in the community leading to worse child outcomes. 

PMID- 27044699
TI  - Poverty, Stress, and Brain Development: New Directions for Prevention and
      Intervention.
AB  - We review some of the growing evidence of the costs of poverty to children's
      neuroendocrine function, early brain development, and cognitive ability. We
      underscore the importance of addressing the negative consequences of poverty
      related adversity early in children's lives, given evidence supporting the
      plasticity of executive functions and associated physiologic processes in
      response to early intervention and the importance of higher order cognitive
      functions for success in school and in life. Finally, we highlight some new
      directions for prevention and intervention that are rapidly emerging at the
      intersection of developmental science, pediatrics, child psychology and
      psychiatry, and public policy. 

PMID- 27044700
TI  - Child Poverty and the Promise of Human Capacity: Childhood as a Foundation for
      Healthy Aging.
AB  - The effect of child poverty and related early life experiences on adult health
      outcomes and patterns of aging has become a central focus of child health
      research and advocacy. In this article a critical review of this proliferating
      literature and its relevance to child health programs and policy are presented.
      This literature review focused on evidence of the influence of child poverty on
      the major contributors to adult morbidity and mortality in the United States, the
      mechanisms by which these associations operate, and the implications for
      reforming child health programs and policies. Strong and varied evidence base
      documents the effect of child poverty and related early life experiences and
      exposures on the major threats to adult health and healthy aging. Studies using a
      variety of methodologies, including longitudinal and cross-sectional strategies,
      have reported significant findings regarding cardiovascular disorders, obesity
      and diabetes, certain cancers, mental health conditions, osteoporosis and
      fractures, and possibly dementia. These relationships can operate through
      alterations in fetal and infant development, stress reactivity and inflammation,
      the development of adverse health behaviors, the conveyance of child chronic
      illness into adulthood, and inadequate access to effective interventions in
      childhood. Although the reviewed studies document meaningful relationships
      between child poverty and adult outcomes, they also reveal that poverty,
      experiences, and behaviors in adulthood make important contributions to adult
      health and aging. There is strong evidence that poverty in childhood contributes
      significantly to adult health. Changes in the content, financing, and advocacy of
      current child health programs will be required to address the childhood
      influences on adult health and disease. Policy reforms that reduce child poverty
      and mitigate its developmental effects must be integrated into broader
      initiatives and advocacy that also attend to the health and well-being of adults.

PMID- 27044701
TI  - Child Poverty: Definition and Measurement.
AB  - This article provides a discussion of what we mean when we refer to 'child
      poverty.' Many images come to mind when we discuss child poverty, but when we try
      to measure and quantify the extent of child poverty, we often use a very narrow
      concept. In this article a variety of poverty measures that are used in the
      United States are described and some of the differences between those measures
      are illustrated. In this article 3 measures are explored in detail: a relative
      measure of poverty that is used more often in an international context, the
      official US poverty measure, and a new supplemental poverty measure (SPM). The
      new measure differs from the other 2 because it takes into account noncash
      benefits that are provided to poor families. These include nutrition assistance
      such as food stamps, subsidized housing, and home energy assistance. The SPM also
      takes account of necessary expenses that families face, such as taxes and
      expenses related to work and health care. Comparing estimates for 2012, the SPM
      showed lower poverty rates for children than the other 2 measures. Because
      noncash benefits help those in extreme poverty, there were also lower percentages
      of children in extreme poverty with resources below half the SPM threshold. These
      results suggest that 2 important measures of poverty, the relative measure used
      in international comparisons, and the official poverty measure, are not able to
      gauge the effect of government programs on the alleviation of poverty, and the
      SPM illustrates that noncash benefits do help families meet their basic needs. 

PMID- 27044702
TI  - Beyond Income Poverty: Measuring Disadvantage in Terms of Material Hardship and
      Health.
AB  - The New York City (NYC) Longitudinal Study of Wellbeing, or "Poverty Tracker," is
      a survey of approximately 2300 NYC residents. Its purpose is to provide a
      multidimensional and dynamic understanding of economic disadvantage in NYC.
      Measures of disadvantage were collected at baseline and a 12-month follow-up, and
      include 3 types of disadvantage: 1) income poverty, using a measure on the basis
      of the new Supplemental Poverty Measure; 2) material hardship, including
      indicators of food insecurity, housing hardship, unmet medical needs, utility
      cutoffs, and financial insecurity; and 3) adult health problems, which can drain
      family time and resources. In this article initial results for NYC families with
      children younger than the age of 18 years are presented. At baseline, 56% of
      families with children had 1 or more type of disadvantage, including 28% with
      income poverty, 39% with material hardship, and 17% with an adult health problem.
      Even among nonpoor families, 33% experienced material hardship and 14% reported
      an adult health problem. Two-thirds of all families faced disadvantage at either
      baseline or follow-up, with 46% experiencing some kind of disadvantage at both
      time points. Respondents with a college education were much less likely to face
      disadvantage. Even after adjusting for educational attainment and family
      characteristics, the families of black and Hispanic respondents had increased
      rates of disadvantage. Considering income poverty alone the extent of
      disadvantage among families with children in NYC is greatly understated. These
      results suggest that in addition to addressing income poverty, policymakers
      should give priority to efforts to reduce material hardship and help families
      cope with chronic physical or mental illness. The need for these resources
      extends far above the poverty line.

PMID- 27044703
TI  - Ending Childhood Poverty in America.

PMID- 27044704
TI  - Trends in Child Poverty Using an Improved Measure of Poverty.
AB  - The official measure of poverty has been used to assess trends in children's
      poverty rates for many decades. But because of flaws in official poverty
      statistics, these basic trends have the potential to be misleading. We use an
      augmented Current Population Survey data set that calculates an improved measure
      of poverty to reexamine child poverty rates between 1967 and 2012. This measure,
      the Anchored Supplemental Poverty Measure, is based partially on the US Census
      Bureau and Bureau of Labor Statistics' new Supplemental Poverty Measure. We focus
      on 3 age groups of children, those aged 0 to 5, 6 to 11, and 12 to 17 years.
      Young children have the highest poverty rates, both historically and today.
      However, among all age groups, long-term poverty trends have been more favorable
      than official statistics would suggest. This is entirely due to the effect of
      counting resources from government policies and programs, which have reduced
      poverty rates substantially for children of all ages. However, despite this
      progress, considerable disparities in the risk of poverty continue to exist by
      education level and family structure. 

PMID- 27044705
TI  - Addressing Child Poverty: How Does the United States Compare With Other Nations?
AB  - Poverty during childhood raises a number of policy challenges. The earliest years
      are critical in terms of future cognitive and emotional development and early
      health outcomes, and have long-lasting consequences on future health. In this
      article child poverty in the United States is compared with a set of other
      developed countries. To the surprise of few, results show that child poverty is
      high in the United States. But why is poverty so much higher in the United States
      than in other rich nations? Among child poverty drivers, household composition
      and parent's labor market participation matter a great deal. But these are not
      insurmountable problems. Many of these disadvantages can be overcome by
      appropriate public policies. For example, single mothers have a very high
      probability of poverty in the United States, but this is not the case in other
      countries where the provision of work support increases mothers' labor earnings
      and together with strong public cash support effectively reduces child poverty.
      In this article we focus on the role and design of public expenditure to
      understand the functioning of the different national systems and highlight ways
      for improvements to reduce child poverty in the United States. We compare
      relative child poverty in the United States with poverty in a set of selected
      countries. The takeaway is that the United States underinvests in its children
      and their families and in so doing this leads to high child poverty and poor
      health and educational outcomes. If a nation like the United States wants to
      decrease poverty and improve health and life chances for poor children, it must
      support parental employment and incomes, and invest in children's futures as do
      other similar nations with less child poverty. 

PMID- 27044706
TI  - Child Poverty: The United Kingdom Experience.
AB  - The United States has long struggled with high levels of child poverty. In 2014,
      2 of 5 (42.9%) of all American children lived in economically insecure households
      and just over 1 in 5 children lived below the official absolute poverty line.
      These rates are high, but not intractable. Evidence from the US Census Bureau's
      Supplemental Poverty Measure, among other sources, shows the effect that public
      investments in cash and noncash transfers can have in reducing child poverty and
      improving child well-being. However, with significant disparities in services and
      supports for children across states and the projected decline of current federal
      spending on children, the United States is an international outlier in terms of
      public investments in children, particularly compared with other high-income
      nations. One such country, the United Kingdom (UK), faced similar child poverty
      challenges in recent decades. At the end of the 20th century, the British Prime
      Minister pledged to halve child poverty in a decade and eradicate it 'within a
      generation.' The Labour Government then set targets and dedicated resources in
      the form of income supplements, employment, child care, and education support.
      Child poverty levels nearly halved against an absolute measure by the end of the
      first decade. Subsequent changes in government and the economy slowed progress
      and have resulted in a very different approach. However, the UK child poverty
      target experience, 15 years in and spanning multiple changes in government, still
      offers a useful comparative example for US social policy moving forward. 

PMID- 27044707
TI  - High US Child Poverty: Explanations and Solutions.

PMID- 27044708
TI  - Child Poverty and the Health Care System.
AB  - The persistence of child poverty in the United States and the pervasive health
      consequences it engenders present unique challenges to the health care system.
      Human capital theory and empirical observation suggest that the increased disease
      burden experienced by poor children originates from social conditions that
      provide suboptimal educational, nutritional, environmental, and parental inputs
      to good health. Faced with the resultant excess rates of pediatric morbidity, the
      US health care system has developed a variety of compensatory strategies. In the
      first instance, Medicaid, the federal-state governmental finance system designed
      to assure health insurance coverage for poor children, has increased its
      eligibility thresholds and expanded its benefits to allow greater access to
      health services for this vulnerable population. A second arm of response involves
      a gradual reengineering of health care delivery at the practice level, including
      the dissemination of patient-centered medical homes, the use of team-based
      approaches to care, and the expansion of care management beyond the practice to
      reach deep into the community. Third is a series of recent experiments involving
      the federal government and state Medicaid programs that includes payment reforms
      of various kinds, enhanced reporting, concentration on high-risk populations, and
      intensive case management. Fourth, pediatric practices have begun to make use of
      specific tools that permit the identification and referral of children facing
      social stresses arising from poverty. Finally, constituencies within the health
      care system participate in enhanced advocacy efforts to raise awareness of
      poverty as a distinct threat to child health and to press for public policy
      responses such as minimum wage increases, expansion of tax credits, paid family
      leave, universal preschool education, and other priorities focused on child
      poverty. 

PMID- 27044709
TI  - Boosting Low-Income Children's Opportunities to Succeed Through Direct Income
      Support.
AB  - Direct income supports have long been known to substantially reduce the extent
      and depth of poverty. Evidence suggests that they can also bolster children's
      opportunities to succeed and enhance long-term mobility. A growing body of
      research, for example, links income from 2 related tax credits for working
      families-the Earned Income Tax Credit and the Child Tax Credit-to benefits for
      children in those families, such as improved birth weight, better school
      outcomes, and increased rates of employment in adulthood. Similarly, the
      introduction of food stamps has been found to improve not only the birth weight
      of infants given access to the program but also their educational achievement, as
      well as indicators of health, well-being, and self-sufficiency decades later.
      These are striking research results for income support that is not typically
      thought of as improving children's health or education. The mechanisms through
      which these income supports lead to such benefits are likely varied and complex,
      but emerging research suggests that helping families with children afford basic
      necessities can reduce the added stress of financial difficulties, preventing
      downstream neuroendocrine and biochemical changes that affect children's longer
      term outcomes. These findings have important implications for policy makers.
      Research suggests that potential weakening of the safety net would not only
      substantially increase poverty, but also have damaging long-term effects on
      children. Policy makers should reject funding cuts and instead strengthen the
      safety net, which this analysis suggests could reduce poverty further and also
      enhance children's opportunities to succeed. 

PMID- 27044710
TI  - The Role of Public Health Insurance in Reducing Child Poverty.
AB  - Over the past 30 years, there have been major expansions in public health
      insurance for low-income children in the United States through Medicaid, the
      Children's Health Insurance Program (CHIP), and other state-based efforts. In
      addition, many low-income parents have gained Medicaid coverage since 2014 under
      the Affordable Care Act. Most of the research to date on health insurance
      coverage among low-income populations has focused on its effect on health care
      utilization and health outcomes, with much less attention to the financial
      protection it offers families. We review a growing body of evidence that public
      health insurance provides important financial benefits to low-income families.
      Expansions in public health insurance for low-income children and adults are
      associated with reduced out of pocket medical spending, increased financial
      stability, and improved material well-being for families. We also review the
      potential poverty-reducing effects of public health insurance coverage. When out
      of pocket medical expenses are taken into account in defining the poverty rate,
      Medicaid plays a significant role in decreasing poverty for many children and
      families. In addition, public health insurance programs connect families to other
      social supports such as food assistance programs that also help reduce poverty.
      We conclude by reviewing emerging evidence that access to public health insurance
      in childhood has long-term effects for health and economic outcomes in adulthood.
      Exposure to Medicaid and CHIP during childhood has been linked to decreased
      mortality and fewer chronic health conditions, better educational attainment, and
      less reliance on government support later in life. In sum, the nation's public
      health insurance programs have many important short- and long-term poverty
      reducing benefits for low-income families with children. 

PMID- 27044711
TI  - A role for FOXO1 in BCR-ABL1-independent tyrosine kinase inhibitor resistance in
      chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) patients who relapse on imatinib due to acquired
      ABL1 kinase domain mutations are successfully treated with second-generation ABL1
      tyrosine kinase inhibitors (ABL-TKIs) such as dasatinib, nilotinib or ponatinib.
      However, ~40% of relapsed patients have uncharacterized BCR-ABL1 kinase
      independent mechanisms of resistance. To identify these mechanisms of resistance
      and potential treatment options, we generated ABL-TKI-resistant K562 cells
      through prolonged sequential exposure to imatinib and dasatinib. Dual-resistant
      K562 cells lacked BCR-ABL1 kinase domain mutations, but acquired other genomic
      aberrations that were characterized by next-generation sequencing and copy number
      analyses. Proteomics showed that dual-resistant cells had elevated levels of
      FOXO1, phospho-ERK and BCL-2, and that dasatinib no longer inhibited substrates
      of the PI3K/AKT pathway. In contrast to parental cells, resistant cells were
      sensitive to growth inhibition and apoptosis induced by the class I PI3K
      inhibitor, GDC-0941 (pictilisib), which also induced FOXO1 nuclear translocation.
      FOXO1 was elevated in a subset of primary specimens from relapsed CML patients
      lacking BCR-ABL1 kinase domain mutations, and these samples were responsive to
      GDC-0941 treatment ex vivo. We conclude that elevated FOXO1 contributes to BCR
      ABL1 kinase-independent resistance experienced by these CML patients and that
      PI3K inhibition coupled with BCR-ABL1 inhibition may represent a novel
      therapeutic approach.

PMID- 27044712
TI  - Development of radiodetection systems towards miniaturised quality control of PET
      and SPECT radiopharmaceuticals.
AB  - The ability to detect radiation in microfluidic devices is important for the on
      chip analysis of radiopharmaceuticals, but previously reported systems have
      largely suffered from various limitations including cost, complexity of
      fabrication, and insufficient sensitivity and/or speed. Here, we present the use
      of sensitive, low cost, small-sized, commercially available silicon
      photomultipliers (SiPMs) for the detection of radioactivity inside microfluidic
      channels fabricated from a range of conventional microfluidic chip substrates. We
      demonstrate the effects of chip material and thickness on the detection of the
      positron-emitting isotope, [(18)F]fluoride, and find that, while the SiPMs are
      light sensors, they are able to detect radiation even through opaque chip
      materials via direct positron and gamma (gamma) ray interaction. Finally, we
      employed the SiPM platform for analysis of the PET (positron emission tomography)
      radiotracers 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) and [(68)Ga]gallium
      citrate, and highlight the ability to detect the gamma ray emitting SPECT (single
      photon emission computed tomography) radiotracer, [(99m)Tc]pertechnetate.

PMID- 27044713
TI  - Breeding Young as a Survival Strategy during Earth's Greatest Mass Extinction.
AB  - Studies of the effects of mass extinctions on ancient ecosystems have focused on
      changes in taxic diversity, morphological disparity, abundance, behaviour and
      resource availability as key determinants of group survival. Crucially, the
      contribution of life history traits to survival during terrestrial mass
      extinctions has not been investigated, despite the critical role of such traits
      for population viability. We use bone microstructure and body size data to
      investigate the palaeoecological implications of changes in life history
      strategies in the therapsid forerunners of mammals before and after the Permo
      Triassic Mass Extinction (PTME), the most catastrophic crisis in Phanerozoic
      history. Our results are consistent with truncated development, shortened life
      expectancies, elevated mortality rates and higher extinction risks amongst post
      extinction species. Various simulations of ecological dynamics indicate that an
      earlier onset of reproduction leading to shortened generation times could explain
      the persistence of therapsids in the unpredictable, resource-limited Early
      Triassic environments, and help explain observed body size distributions of some
      disaster taxa (e.g., Lystrosaurus). Our study accounts for differential survival
      in mammal ancestors after the PTME and provides a methodological framework for
      quantifying survival strategies in other vertebrates during major biotic crises.

PMID- 27044714
TI  - The analysis outlining the occurrence and consequences of accidents in the work
      environment of the firefighters employed by the State Fire Service in Poland in
      2008-2013.
AB  - BACKGROUND: Due to the specifics of their work and to being exposed to a wide
      range of hazards, firefighters working for the State Fire Service (SFS) face the
      risk of work-related accidents more often than members of other occupational
      groups. The aim of this paper is to analyze the occurrence and consequences of
      accidents in the work environment of the SFS officers in Poland between the years
      2008-2013. MATERIAL AND METHODS: The material analyzed is based on aggregate data
      collected by the Headquarters of the State Fire Service. Figures regarding
      accidents in the period between 1 January 2008 and 31 December 2013 show that
      8518 work-related accidents occurred in that period and 8635 people were injured.
      RESULTS: The data shows that neither the number of accidents nor their frequency
      indicator underwent any significant fluctuations over the 6 years under
      consideration. The group that is most exposed to accidents on duty in the
      profession includes active firefighters serving in rescue and fire extinguishment
      divisions. According to the data, the greatest number of trauma incidents in the
      SFS between the years 2008-2013 occurred during sporting activities. The
      predominant cause of these was inappropriate behavior or the lack of proper care.
      The most frequent injuries sustained during the accidents were broken or
      fractured bones and sprained joints. CONCLUSIONS: Accidents on duty occur
      significantly more often when firefighters are at their stations, during sporting
      classes, exercises or maneuvers, than in the course of actual rescue operations.
      The firefighters of the State Fire Services are insufficiently prepared for their
      sporting activities.

PMID- 27044715
TI  - Evaluation of chosen determinants of the positive practice environments (PPE) at
      Polish nursing wards.
AB  - BACKGROUND: At many Polish hospitals, insufficient attention is given to positive
      work environment. In many cases nurses, similarly to the representatives of other
      professional groups, are not provided with facilities or tools to perform their
      professional tasks in safe conditions. The aspects of recruitment and retention
      of employees are often ignored. The aim of this study has been to assess the
      chosen determinants of work environment of nurses in Poland using the concept of
      the Positive Practice Environments (PPE). MATERIAL AND METHODS: The survey was
      carried out from 2008 to 2011 among 1049 nursing students of 3 randomly selected
      public medical universities that provided nursing education at the graduate level
      of the Master of Science. All the people qualified for the study group were
      practising nurses or midwives. The Polish Nursing Association coordinated the
      project, obtained the tool, translated it and adjusted it to the Polish
      conditions. The areas covered in the survey were: a place of employment, selected
      physical and social elements influencing the work conditions, and biographical
      information. RESULTS: Access to as many as 8 factors identified as attributes of
      friendly environments was found unsatisfactory by over 50% of the nurses. For the
      purpose of objective assessment, the results were compared with the results
      obtained in the group of nurses in England. CONCLUSIONS: The majority of the
      surveyed nurses were not satisfied with their work environments. Polish nurse
      managers should ensure that aspects of recognized attributes of friendly,
      positive practice environments for nurses are established to support nurses'
      satisfaction as a pre-condition for patients' safety.

PMID- 27044716
TI  - Disordered eating, amenorrhea, and substance use and misuse among professional
      ballet dancers: Preliminary analysis.
AB  - BACKGROUND: Substance use and misuse (SUM), eating disorders (ED) and consequent
      amenorrhea (AM) occur frequently in professional ballet dancing. The objective of
      this study has been to explore the prevalence and association between ED, AM and
      SUM in ballet. MATERIAL AND METHODS: The sample comprised 21 ballet dancers,
      23.1+/-4.5 years old, members of the professional National Ballet Ensemble from
      Croatia. Variables were collected by questionnaires examining SUM, occurrence of
      amenorrhea, and corresponding ballet-specific and socio-demographic factors
      (Questionnaire on Substance Use - QSU) and the level of ED (Brief Eating Disorder
      in Athletes Questionnaire - BEDA-Q). RESULTS: Smoking is prevalent in 40% of
      dancers (25% smoke on a daily basis), 36% often use analgesics, and 25% engage in
      binge drinking at least once a month. Smoking and binge drinking are less
      frequent in ballerinas with a higher academic level (r = 0.60 and r = 0.54 for
      binge drinking and smoking, respectively; p < 0.05). Alcohol drinking is higher
      among dancers who consume analgesics more often and those with a higher BEDA-Q
      score (r = 0.53 and r = 0.54 for analgesics and BEDA-Q, respectively; p < 0.05).
      Amenorrhea is more prevalent among those dancers with a higher BEDA-Q score.
      Women who consume nutritional supplements are less likely to use analgesics (Mann
      Whitney U test = 2.11; p < 0.05). CONCLUSIONS: Efforts seeking to prevent ED in
      ballet should target dancers who consume alcohol to a greater extent. Future
      studies should specifically explore the less frequent consumption of analgesics
      among dancers who consume nutritional supplements.

PMID- 27044717
TI  - [Psychometric properties of the Polish version of the Oldenburg Burnout Inventory
      (OLBI)].
AB  - BACKGROUND: The objective of this study was to test the psychometric properties
      of the Polish version of the Oldenburg Burnout Inventory (OLBI) - its factor
      structure, reliability, validity and standard norms. MATERIAL AND METHODS: The
      study was conducted on 3 independent samples of 1804, 366 and 48 workers employed
      in social service and general service professions. To test the OLBI structure the
      exploratory factor analysis was conducted. The reliability was assessed by means
      of Cronbach's alpha coefficient (the internal consistent) and test-retest (the
      stability over time) method, with a 6-week follow-up. The construct validity of
      the OLBI was tested by means of correlation analysis, using perceived stress and
      work engagement as the criterion variables. RESULTS: The result of the factor
      analysis confirmed a 2-factor structure of the Inventory but the construction of
      each factor differed from that in the OLBI original version. Therefore, 2
      separate factor analyses - each for the single component of job burnout
      (exhaustion and disengagement from work) - were conducted. The analyses revealed
      that each of the components consisted of 2 subscales. The reliability of the OLBI
      was supported by 2 methods. It was also proved that job burnout and its 2
      components, exhaustion and disengagement from work, were positively correlated
      with perceived stress and negatively correlated with work engagement and its 3
      components - vigor, absorption and dedication. CONCLUSIONS: Despite certain
      limitations the Polish version of the OLBI shows satisfactory psychometric
      properties and it can be used to measure job burnout in Polish conditions.

PMID- 27044718
TI  - [Studies on an efficient method for determining 3,3'-dimethylbenzidine in the
      workplace air].
AB  - BACKGROUND: 3,3'-Dimethylbenzidene (DMB) is a substance classified into the group
      of carcinogens. The value of maximum admissible concentration for this substance
      in the workplace air is not specified in Poland. Bearing in mind that DMB is used
      in domestic companies there is a need to develop a sensitive method for
      determining 3,3'-dimethylbenzidine in the work environment. MATERIAL AND METHODS:
      The method consists in passing DMB-containing air through sulfuric acid-treated
      glass fiber filters, washing out the substance settled on the filter, using water
      and solution of sodium hydroxide, liquid-liquid extraction with toluene,
      replacing dissolvent with acetonitrile and analyzing the obtained solution.
      Studies were performed using high-performance liquid chromatography (HPLC)
      technique. An Agilent Technologies chromatograph, series 1200, with a diode-array
      detector (DAD) and a fluorescence detector (FLD) was used in the experiment. In
      the test, an Ultra C18 column of dimensions: 250*4.6 mm, particle diameter (dp) =
      5 MUm (Restek) was applied. RESULTS: The method is linear (r = 0.999) within the
      investigated working range of concentration 1.08-21.6 MUg/ml, which is equivalent
      to air concentrations 2-40 MUg/m3 for a 540 l air sample. The limit of detection
      (LOD) of quantification determination is 5.4 ng/ml and the limit of
      quantification (LOQ) - 16.19 ng/ml. CONCLUSIONS: The analytical method described
      in this paper allows for selective determination of 3,3'-dimethylbenzidine in the
      workplace air in the presence of 1,4-phenylenediamine, benzidine, aniline, 3,3'
      dimethoxybenzidine, 2-nitrotoluene, 3,3'-dichlorobenzidine and azobenzene. The
      method is characterized by good precision and good accuracy, it also meets the
      criteria for procedures involving the measurement of chemical agents, listed in
      EN 482:2012.

PMID- 27044719
TI  - [Offshore substation workers' exposure to harmful factors - Actions minimizing
      risk of hazards].
AB  - The current development of electric power industry in Poland, especially in the
      field of renewable energy sources, including wind power, brings about the need to
      introduce legislation on new work environment. The development of occupational
      safety and health (OSH) regulations that must be met by new workplaces, such as
      offshore substations becomes necessary in view of the construction of modern
      offshore wind power plants - offshore wind farms. Staying on offshore substation
      is associated with an increased exposure to harmful health factors: physical,
      chemical, biological and psychophysical. The main sources of health risks on
      offshore substations are: temperature, electromagnetic field, noise from
      operating wind turbines, direct and alternating current, chemicals, Legionella
      bacteria and social isolation of people. The aim of this article is to draw
      attention to the problem of offshore substation workers' exposure to harmful
      factors and to present methods of preventing and reducing the risk-related
      adverse health effects. In this paper, there are identified and described risks
      occurring on offshore substations (fire, explosion, lightning, accidents at
      work). Some examples of the means and the methods for reducing the negative
      impact of exposure on the human health are presented and discussed. The article
      also highlights the need to develop appropriate laws and health and safety
      regulations concerning the new working environment at the offshore substations.
      The review of researches and international standards shows that some of them can
      be introduced into the Polish labor market.

PMID- 27044720
TI  - [Tick-borne diseases in Poland: Prevalence and difficulties in diagnostics].
AB  - The article presents an overview of diagnostics of tick-borne diseases in Poland,
      which form one of the most prevalent group of occupational illnesses in the
      Polish area. This is a current issue due to a constantly growing number of tick
      borne infections, i.e., Lyme borreliosis, tick-borne encephalitis, tularemia, Q
      fever, human granulocytic anaplasmosis and babesiosis. The scale of the problem
      is well illustrated by the latest reports of the Polish National Institute of
      Public Health - National Institute of Hygiene (NIPH - NIH). The article also
      covers the taxonomy of vectors of etiological factors, as well as their
      reservoirs and possible transmission to humans. The highest risk of tick-borne
      infection is particularly connected with people either resting or working in the
      forest or meadow surroundings (i.e., foresters, farmers, hunters). The article
      contains up-to-date data on epidemiology, etiopathogenesis, symptomatology,
      laboratory medicine and factors affecting the credibility of results according to
      current recommendations of the Polish Society of Epidemiology and Physicians of
      Infectious Diseases and the Polish National Chamber of Laboratory Diagnosticians.
      The presented review focuses on modern laboratory techniques used in difficult
      diagnostics of tick-borne diseases, mainly diagnostics algorithms, pre-analytical
      phase (type of biological material) and analytical phase of diagnostics
      (reference methods, efficacy of different techniques, interfering factors, proper
      diagnostic procedures).

PMID- 27044721
TI  - [Arsenic - Poison or medicine?].
AB  - Arsenic (As) is commonly known as a poison. Only a few people know that As has
      also been widely used in medicine. In the past years As and its compounds were
      used as a medicine for the treatment of such diseases as diabetes, psoriasis,
      syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in
      the treatment of patients with acute promyelocytic leukemia. The International
      Agency for Research on Cancer (IARC) has recognized arsenic as an element with
      carcinogenic effect evidenced by epidemiological studies, but as previously
      mentioned it is also used in the treatment of neoplastic diseases. This
      underlines the specificity of the arsenic effects. Arsenic occurs widely in the
      natural environment, for example, it is present in soil and water, which
      contributes to its migration to food products. Long exposure to this element may
      lead to liver damages and also to changes in myocardium. Bearing in mind that
      such serious health problems can occur, monitoring of the As presence in the
      environmental media plays a very important role. In addition, the occupational
      risk of As exposure in the workplace should be identified and checked. Also the
      standards for As presence in food should be established. This paper presents a
      review of the 2015 publications based on the Medical database like PubMed and
      Polish Medical Bibliography. It includes the most important information about
      arsenic in both forms, poison and medicine.

PMID- 27044722
TI  - [A need to implement new tools for diagnosing tobacco-addition syndrome and
      readiness/motivation to quit smoking in the working-age population in Poland].
AB  - High rates of tobacco use is still observed in working-age population in Poland.
      The present level of the state tobacco control has been achieved through adopting
      legal regulations and population-based interventions. In Poland a sufficient
      contribution of health professionals to the diagnosis of the tobacco-addition
      syndrome (TAS) and the application of the 5A's (ask, advice, assess, assist,
      arrange follow-up) brief intervention, has not been confirmed by explicit
      research results. Systemic solutions of the health care system of the
      professional control, specialist health care, health professional trainings and
      reference centres have not as yet been elaborated. The tools for diagnosing
      tobacco dependence and motivation to quit smoking, developed over 30 years ago
      and recommended by experts to be used in clinical and research practice, have not
      met the current addiction criteria. In this paper other tools than those
      previously recommended - tests developed in the first decade of the 21st century
      (including Cigarette Dependence Scale and Nicotine Dependence Syndrome Scale),
      reflecting modern concepts of nicotine dependence are presented. In the
      literature on the readiness/motivation to change health behaviors, a new approach
      dominates. The motivational interviewing (MI) by Miller and Rollnick concentrates
      on a smoking person and his or her internal motivation. Motivational interviewing
      is recommended by the World Health Organization as a 5R's (relevance, risks,
      rewards, roadblocks, repetition) brief motivational advice, addressed to tobacco
      users who are unwilling to make a quit attempt. In Poland new research studies on
      the implementation of new diagnostic tools and updating of binding guidelines
      should be undertaken, to strengthen primary health care in treating tobacco
      dependence, and to incorporate MI and 5R's into trainings in TAS diagnosing and
      treating addressed to health professionals.

PMID- 27044723
TI  - Papain-induced occupational rhinoconjunctivitis and asthma - A case report.
AB  - This report presents a case of occupational asthma, rhinitis and conjunctivitis
      to papain in a 50-year-old herbs and spices packer, with documented increased
      eosinophilia in induced sputum and in the nasal lavage fluids after a specific
      inhalation challenge test (SICT) and specific nasal challenge test (SNCT) with
      this enzyme. Immunoglobulin E-mediated (IgE) sensitization to papain was
      confirmed by positive results of a skin prick test with specific solution.
      Specific inhalation and nasal challenge tests demonstrated a direct and
      significant link between the exposure to this protease and the allergic response
      from the respiratory system. Additionally, the SNCT induced a severe reaction of
      the conjunctivae and a significant increase in the count of eosinophils in tears,
      despite the lack of direct contact of the allergen with the conjunctiva.

PMID- 27044724
TI  - Relationship Between Iodine Concentration in Maternal Colostrum and
      Neurobehavioral Development of Infants in Shanghai, China.
AB  - It is well known that iodine plays an important role in the process of early
      growth and development of most organs, especially the brain. However, iodine
      concentration in the colostrum and its association with the neurobehavioral
      development of infants remains unclear. Colostrums from 150 women were collected,
      and their iodine concentrations were measured. The median colostrum iodine level
      was 187.8 MUg/L. The Bayley Scales of Infant and Toddler Development-III test was
      performed when the infants were about 18 months. The mean cognitive, language,
      and motor composite scores were 105.3 +/- 9.8, 105.2 +/- 11.1, and 104.6 +/- 6.7,
      respectively. And the mean scores of the 5 subtests were 11.1 +/- 2.0, 9.3 +/-
      2.0, 12.4 +/- 2.3, 11.1 +/- 1.2, and 10.4 +/- 1.2, respectively. No statistically
      significant difference was observed in the cognition, language, or motor
      development of infants across different levels of colostrum iodine. After
      adjusting for a range of confounding factors, colostrum iodine concentration was
      a predictor of motor development, specifically gross motor development.

PMID- 27044725
TI  - A general strategy for expanding polymerase function by droplet microfluidics.
AB  - Polymerases that synthesize artificial genetic polymers hold great promise for
      advancing future applications in synthetic biology. However, engineering natural
      polymerases to replicate unnatural genetic polymers is a challenging problem.
      Here we present droplet-based optical polymerase sorting (DrOPS) as a general
      strategy for expanding polymerase function that employs an optical sensor to
      monitor polymerase activity inside the microenvironment of a uniform synthetic
      compartment generated by microfluidics. We validated this approach by performing
      a complete cycle of encapsulation, sorting and recovery on a doped library and
      observed an enrichment of ~1,200-fold for a model engineered polymerase. We then
      applied our method to evolve a manganese-independent alpha-L-threofuranosyl
      nucleic acid (TNA) polymerase that functions with >99% template-copying fidelity.
      Based on our findings, we suggest that DrOPS is a versatile tool that could be
      used to evolve any polymerase function, where optical detection can be achieved
      by Watson-Crick base pairing. 

PMID- 27044726
TI  - Pattern of in-patient neurologic review: An experience from a Tertiary Hospital
      North-Western Nigeria.
AB  - BACKGROUND: Increase in neurologic diseases burden has increased the demand for
      neurology services globally, despite the shortcomings of shortage and
      maldistribution of neurologists worldwide, including Sub-Saharan Africa. This has
      placed significant pressure on the few available neurologists to provide optimal
      and effective services in our resource-challenged settings. METHODS: Neurology
      referrals were prospectively reviewed over a period of 3 months. Sociodemographic
      characteristics of the patients, the initial diagnosis by the requesting team,
      the reasons for the consult/referral, the requesting personnel, duration of
      hospital stay before request, the time interval between receiving the request and
      review, the working and final diagnosis after the review, and the diagnostic
      outcome of neurologic review were analyzed using Predictive Analytics Software(r)
      version 18.0.0 for Windows (Chicago, Illinois, USA). RESULTS: Fifty-three hand
      written in-patient requests were reviewed over the period of study given an
      average rate of 4.4/week. The mean age was 50.8 +/- 16.1 years, and the median
      length of stay before a review was 1 day (interquartile range: 1-2.5 days).
      Diagnostic outcome of the reviews were; new diagnoses in 4 (11.3%), the incorrect
      diagnosis changed in 8 (15.1%), contribution to the differential diagnosis in 15
      (28.3%), and contribution to management plans in 24 (45.3%) patients. The
      association between diagnostic outcomes and mortality in our study was not
      statistically significant (chi2 = 6.66, P = 0.08). CONCLUSION: Our study showed
      that in-patient neurologic reviews led to significant improvement in diagnostic
      and management plans. Appropriate policy guidelines should focus more on
      efficient ways of maximizing benefits of these reviews to patients without
      overburdening the few available neurologists in our environment.

PMID- 27044727
TI  - Retinal nerve fiber layer thickness measurements of normal Northern Nigerian
      adults using optical coherence tomography.
AB  - OBJECTIVE: To assess retinal nerve fiber layer (RNFL) thickness measurements of
      normal Northern Nigerian adults using optical coherence tomography (OCT).
      SUBJECTS AND METHODS: The OCT procedure was carried out with the Carl Zeiss
      Stratus OCT Model 3000 software version 4.0 (Carl Zeiss Meditec AG, Jena,
      Germany). The fast RNFL scan protocol was used to obtain RNFL thickness
      measurements. Student's t-test was used to compare mean RNFL thickness values. P
      <= 0.05 was considered as statistically significant. Average RNFL thickness was
      correlated with age. RESULTS: Two hundred and twenty eyes of 110 subjects aged 18
      51 years were examined. The average RNFL thickness was 104.17 +/- 10.71 MUm. The
      mean values for the RNFL thickness were 129.15 +/- 16.87 MUm, 135.34 +/- 20.40
      MUm, 85.10 +/- 23.60 MUm, and 67.19 +/- 13.27 MUm for the inferior, superior,
      nasal, and temporal quadrants, respectively. A statistically significant
      difference was found between males and females for the mean RNFL thickness (t =
      3.30, P = 0.001) and for the mean superior and inferior RNFL thickness. There was
      a statistically significant difference between right and left eyes (t = 3.73, P =
      0.001) for the mean RNFL thickness. A negative correlation was found between RNFL
      thickness and age (r = -0.313, P = 0.002). CONCLUSION: Normal RNFL thickness
      measurements in healthy Nigerian adults are presented. The RNFL was found to be
      thicker in females and in right eyes. The values were comparable to those of the
      Indian population but higher than some Caucasian values.

PMID- 27044728
TI  - Contraceptive choices among grand multiparous women at Murtala Mohammed
      Specialist Hospital, Kano.
AB  - BACKGROUND: Grand multiparity is known to be associated with pregnancy
      complications. Nigeria with a contraceptive prevalence of <15% and culture of
      early marriage in the northern part of the country, many women get to grand
      multiparity early in their obstetric carriers. These women contribute
      significantly to the bad obstetric performance indices in the country. The
      present study was to explore the contraceptive choices among grand multiparous
      women. METHODS: This study was a descriptive cross-sectional study among grand
      multiparous women attending an antenatal clinic. Data were collected on
      sociodemographic characteristics, contraceptive choices, and factors that
      influence such choices. The data were analyzed using Statistical Package for the
      Social Sciences version 18. RESULTS: There were 219 respondents. The mean age was
      33.05 +/- 3.17, and the mean parity was 6.48 +/- 1.83. Most of the respondents
      (208, 95.50%) were aware of modern contraceptive methods, and oral contraceptive
      was the method of most of the respondents (197, 90.00%). Only 92 (42.00%) were
      currently using a modern contraceptive method. Being convenient for the lifestyle
      was the reason for the choice of a contraceptive method by many of the
      respondents (42, 19.10%). CONCLUSION: There was high awareness of modern
      contraceptive methods; however, there was low use prevalence among respondents,
      and the desire for more pregnancy was the reason for the nonuse.

PMID- 27044729
TI  - Pattern and outcome of renal admissions at the University of Port Harcourt
      Teaching Hospital, Nigeria: A 4 years review.
AB  - BACKGROUND/OBJECTIVE: Renal diseases constitute an enormous health burden
      globally, more so in developing countries. This report determines the patterns
      and outcomes of renal diseases in the medical wards of the University Teaching
      Hospital in Nigeria. METHODS: A retrospective study of patients admitted for
      renal disease in 4 years. RESULTS: A total of 3841 patients were admitted to the
      medical wards, of which 590 (15.4%) had renal disease. Mean age of patients was
      46 +/- 15 years. Median duration of admission was 14 days (range 1-92 days). The
      most prevalent renal diseases were hypertensive nephropathy, diabetic
      nephropathy, chronic glomerulonephritis, and HIV-related renal disease
      constituting 22.8%, 16.6%, 14.4%, and 13.1%, respectively. Acute kidney injury
      constituted 12.4% of renal admissions. Analysis of outcome showed that 317
      (53.7%) were discharged home, 49 (8.3%) patients discharged themselves against
      medical advice or absconded while 120 (20.3%) patients died of the disease. The
      highest mortality rate (22.5%) was observed among patients with the HIV-related
      renal disease. CONCLUSION: Renal disease remains a significant cause of morbidity
      and mortality in Port Harcourt, Southern Nigeria. This underscores an urgent need
      to institute measures for prevention and early detection of renal disease and
      reduction of its burden.

PMID- 27044730
TI  - Study of clinical and radiological profile and outcome in patients of
      intracranial hemorrhage.
AB  - BACKGROUND: Incidence of intracerebral hemorrhage (ICH) is twice as high as in
      Western countries. Prognostic factors for predicting function outcome and
      mortality play a major role in determining the treatment outcome. METHODS: A
      prospective study of male and female patients >=12 years with primary
      nontraumatic intracranial hemorrhage were included. Hemorrhage caused by trauma,
      anticoagulant or thrombolytic drugs, brain tumor, saccular arterial aneurysm or
      vascular malformation were excluded. Functional outcome of patients was
      determined by modified Rankin's scale. Glasgow Coma Scale (GCS) score and ICH
      score were calculated for each patient. RESULTS: Hypertension was present in 45
      out of 49 patients (92%) with ICH of basal ganglia. Hypertension was
      significantly associated with worst clinical outcome. Mortality was high if the
      patient was comatose/stuporous compared to drowsy state (P < 0.0001). Mortality
      was found to be high when the size exceeded 30 cm3. High ICH score, low GCS score
      at the time of admission, presence of intraventricular hemorrhage, and midline
      shift were significantly associated with poor clinical outcome. CONCLUSIONS:
      Intracranial hemorrhage can be deleterious if present with low GCS score, high
      ICH score, intraventricular extension, and midline shift.

PMID- 27044731
TI  - Outcome of anesthesia in elective surgical patients with comorbidities.
AB  - BACKGROUND: Presence of comorbidity in surgical patients may be associated with
      adverse perioperative events and increased the risk of morbidity and mortality.
      This audit was conducted to determine the frequencies of comorbidities in
      elective surgical patients and the outcome of anesthesia in a Tertiary Hospital
      in Nigeria. MATERIALS AND METHODS: Observational study of a cross-section of
      adult patients scheduled for elective surgery over a 6-month period. A
      standardized questionnaire was used to document patients' demographics, the
      presence of comorbidity and type, surgical diagnosis, anesthetic technique,
      intraoperative adverse events, and outcome of anesthesia. The questionnaire was
      administered pre- and post-operatively to determine the effects of the
      comorbidities on the outcome of anesthesia. RESULTS: One hundred and sixty-five
      adult patients aged between 18 and 84 years were studied. There were 89 (53.9%)
      females and 76 (46.1%) males. Forty-five (27.3%) have at least one comorbidity.
      Hypertension was the most common (48.8%) associated illness. Other comorbidities
      identified include anemia (17.8%), asthma (8.9%), diabetes mellitus (6.7%),
      chronic renal disease (6.7%), and others. The perioperative period was uneventful
      in majority of patients (80.6%) despite the presence of comorbidities.
      Intraoperative adverse events include hypotension, hypertension, shivering, and
      vomiting. No mortality was reported. CONCLUSION: Hypertension was the most common
      comorbidity in this cohort of patients. The presence of comorbidity did not
      significantly affect the outcome of anesthesia in elective surgical patients.

PMID- 27044732
TI  - Co-existing autosomal dominant polycystic kidney disease and nephrotic syndrome
      in a Nigerian patient with lupus nephritis.
AB  - A little over 30 cases on co-existing nephrotic syndrome and autosomal dominant
      polycystic kidney disease (ADPKD) have been reported from different regions of
      the world since 1957. We present a case report on co-existence of nephrotic
      syndrome (secondary to lupus nephritis) with ADPKD in a 24-year-old woman from
      Nigeria. She was positive for anti-double stranded DNA. Renal histology showed
      International Society of Nephrology/Renal Pathology Society Class II lupus
      nephritis. The co-existence of nephrotic syndrome and ADPKD may have been
      overlooked in Africa in the past. There is a need to screen for nephrotic
      syndrome in patients with ADPKD among clinicians in the African setting. 

PMID- 27044733
TI  - Spinocerebellar ataxia type-7: Report of a family in Northwest Nigeria.
AB  - Spinocerebellar ataxia type-7 (SCA7) is a cytosine-adenine-guanine (CAG) repeat
      polyglutamine disorder characterized by progressive degeneration of the
      cerebellum, brainstem, spinal cord, and retina. Clinical features include
      progressive ataxia, visual loss, pyramidal weakness, sensory impairment, and
      dementia. Among the autosomal dominant cerebellar ataxias, SCA7 is relatively
      common in Scandinavia and South Africa but rare worldwide and is not previously
      reported in Nigeria. In this study, we describe a family in Katsina State,
      Northwest Nigeria, with nine individuals across three generations affected by the
      SCA7 phenotype. Analysis of DNA from proband and two affected relatives revealed
      39 CAG repeat expansions in one allele of ataxin-7 in each. 

PMID- 27044734
TI  - Factors associated with nurses' knowledge and prescriptive attitudes toward
      emergency contraception in Northern Nigeria.

PMID- 27044735
TI  - Male breast cancer: An often forgotten diagnosis.

PMID- 27044736
TI  - Erratum: Nurses' knowledge of care of chest drain: A survey in a Nigerian
      semiurban university hospital.

PMID- 27044737
TI  - Zwitterionic Modifications for Enhancing the Antifouling Properties of
      Poly(vinylidene fluoride) Membranes.
AB  - The development of effective antibiofouling membranes is critical for many
      scientific interests and industrial applications. However, the existing available
      membranes often suffer from the lack of efficient, stable, and scalable
      antifouling modification strategy. Herein, we designed, synthesized, and
      characterized alternate copolymers of p(MAO-DMEA) (obtained by reaction between
      poly(maleic anhydride-alt-1-octadecene) and N,N-dimethylenediamine) and p(MAO
      DMPA) (obtained by reaction between poly(maleic anhydride-alt-1-octadecene) and 3
      (dimethylamino)-1-propylamine) of different carbon space length (CSL) using a
      ring-opening zwitterionization. We coated these copolymers on poly(vinylidene
      fluoride) (PVDF) membranes using a self-assembled anchoring method. Two important
      design parameters-the CSL of polymers and the coating density of polymers on
      membrane-were extensively examined for their effects on the antifouling
      performance of the modified membranes using a series of protein, cell, and
      bacterial assays. Both zwitterionic-modified membranes with different coating
      densities showed improved membrane hydrophilicity, increased resistance to
      protein, bacteria, blood cells, and platelet adsorption. However, while p(MAO
      DMEA) with two CSLs and p(MAO-DMPA) with three CSLs only differ by one single
      carbon between the amino and ammonium groups, such subtle structural difference
      between the two polymers led to the fact that the membranes self-assembled with
      MAO-DMEA outperformed those modified with MAO-DMPA in all aspects of surface
      hydration, protein and bacteria resistance, and blood biocompatibility. This work
      provides an important structural-based design principle: a subtle change in the
      CSL of polymers affects the surface and antifouling properties of the membranes.
      It can help to achieve the design of more effective antifouling membranes for
      blood contacting applications.

PMID- 27044738
TI  - Hyperchloremia as a confounding variable in fluid therapy studies.

PMID- 27044739
TI  - Electrogenic Steps Associated with Substrate Binding to the Neuronal Glutamate
      Transporter EAAC1.
AB  - Glutamate transporters actively take up glutamate into the cell, driven by the co
      transport of sodium ions down their transmembrane concentration gradient. It was
      proposed that glutamate binds to its binding site and is subsequently transported
      across the membrane in the negatively charged form. With the glutamate binding
      site being located partially within the membrane domain, the possibility has to
      be considered that glutamate binding is dependent on the transmembrane potential
      and, thus, is electrogenic. Experiments presented in this report test this
      possibility. Rapid application of glutamate to the wild-type glutamate
      transporter subtype EAAC1 (excitatory amino acid carrier 1) through photo-release
      from caged glutamate generated a transient inward current, as expected for the
      electrogenic inward movement of co-transported Na(+) In contrast, glutamate
      application to a transporter with the mutation A334E induced transient outward
      current, consistent with movement of negatively charged glutamate into its
      binding site within the dielectric of the membrane. These results are in
      agreement with electrostatic calculations, predicting a valence for glutamate
      binding of -0.27. Control experiments further validate and rule out other
      possible explanations for the transient outward current. Electrogenic glutamate
      binding can be isolated in the mutant glutamate transporter because reactions,
      such as glutamate translocation and/or Na(+) binding to the glutamate-bound
      state, are inhibited by the A334E substitution. Electrogenic glutamate binding
      has to be considered together with other voltage-dependent partial reactions to
      cooperatively determine the voltage dependence of steady-state glutamate uptake
      and glutamate buffering at the synapse.

PMID- 27044740
TI  - The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62
      Modulates Complement Activation.
AB  - Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine
      (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan
      terminally substituted with PCh. The PCh component is biologically important
      because it is required for immunomodulatory effects. We showed that most ES-62
      was bound to a single protein, C-reactive protein (CRP), in normal human serum,
      displaying a calcium-dependent, high-avidity interaction and ability to form
      large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently
      activate complement as far as the C3 convertase stage in comparison with PCh-BSA
      and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture
      assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all
      activated C1 and generated C4b to similar extents. However, a C2a active site was
      not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was
      far less efficient for ES-62-containing complexes. We proposed that failure of C2
      cleavage was due to the flexible nature of carbohydrate-bound PCh and that
      reduced proximity of the C1 complex was the reason that C2 was poorly cleaved.
      This was confirmed using synthetic analogues that were similar to ES-62 only in
      respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early
      complement components, such as the rate-limiting C4, following CRP interaction
      and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan
      represents a novel mechanism for subversion of complement activation. These data
      illustrate the importance of the rate-limiting C4/C2 stage of complement
      activation and reveal a new addition to the repertoire of ES-62 immunomodulatory
      mechanisms with possible therapeutic applications.

PMID- 27044741
TI  - Phosphorylation of Yeast Pah1 Phosphatidate Phosphatase by Casein Kinase II
      Regulates Its Function in Lipid Metabolism.
AB  - Pah1 phosphatidate phosphatase in Saccharomyces cerevisiae catalyzes the
      penultimate step in the synthesis of triacylglycerol (i.e. the production of
      diacylglycerol by dephosphorylation of phosphatidate). The enzyme playing a major
      role in lipid metabolism is subject to phosphorylation (e.g. by Pho85-Pho80,
      Cdc28-cyclin B, and protein kinases A and C) and dephosphorylation (e.g. by Nem1
      Spo7) that regulate its cellular location, catalytic activity, and
      stability/degradation. In this work, we show that Pah1 is a substrate for casein
      kinase II (CKII); its phosphorylation was time- and dose-dependent and was
      dependent on the concentrations of Pah1 (Km = 0.23 MUm) and ATP (Km = 5.5 MUm).
      By mass spectrometry, truncation analysis, site-directed mutagenesis,
      phosphopeptide mapping, and phosphoamino acid analysis, we identified that >90%
      of its phosphorylation occurs on Thr-170, Ser-250, Ser-313, Ser-705, Ser-814, and
      Ser-818. The CKII-phosphorylated Pah1 was a substrate for the Nem1-Spo7 protein
      phosphatase and was degraded by the 20S proteasome. The prephosphorylation of
      Pah1 by protein kinase A or protein kinase C reduced its subsequent
      phosphorylation by CKII. The prephosphorylation of Pah1 by CKII reduced its
      subsequent phosphorylation by protein kinase A but not by protein kinase C. The
      expression of Pah1 with combined mutations of S705D and 7A, which mimic its
      phosphorylation by CKII and lack of phosphorylation by Pho85-Pho80, caused an
      increase in triacylglycerol content and lipid droplet number in cells expressing
      the Nem1-Spo7 phosphatase complex. 

PMID- 27044742
TI  - Proteomic Characterization of Inhibitory Synapses Using a Novel pHluorin-tagged
      gamma-Aminobutyric Acid Receptor, Type A (GABAA), alpha2 Subunit Knock-in Mouse.
AB  - The accumulation of gamma-aminobutyric acid receptors (GABAARs) at the
      appropriate postsynaptic sites is critical for determining the efficacy of fast
      inhibitory neurotransmission. Although we know that the majority of synaptic
      GABAAR subtypes are assembled from alpha1-3, beta, and gamma2 subunits, our
      understanding of how neurons facilitate their targeting to and stabilization at
      inhibitory synapses is rudimentary. To address these issues, we have created
      knock-in mice in which the pH-sensitive green fluorescent protein (GFP) and the
      Myc epitope were introduced to the extracellular domain of the mature receptor
      alpha2 subunit (pHalpha2). Using immunoaffinity purification and mass
      spectroscopy, we identified a stable complex of 174 proteins that were associated
      with pHalpha2, including other GABAAR subunits, and previously identified
      receptor-associated proteins such as gephyrin and collybistin. 149 of these
      proteins were novel GABAAR binding partners and included G-protein-coupled
      receptors and ion channel subunits, proteins that regulate trafficking and
      degradation, regulators of protein phosphorylation, GTPases, and a number of
      proteins that regulate their activity. Notably, members of the postsynaptic
      density family of proteins that are critical components of excitatory synapses
      were not associated with GABAARs. Crucially, we demonstrated for a subset of
      these novel proteins (including cullin1, ephexin, potassium channel
      tetramerization domain containing protein 12, mitofusin2, metabotropic glutamate
      receptor 5, p21-activated kinase 7, and Ras-related protein 5A) bind directly to
      the intracellular domains of GABAARs, validating our proteomic analysis. Thus,
      our experiments illustrate the complexity of the GABAAR proteome and enhance our
      understanding of the mechanisms neurons use to construct inhibitory synapses.

PMID- 27044743
TI  - Inorganic Phosphate Limitation Modulates Capsular Polysaccharide Composition in
      Mycobacteria.
AB  - Mycobacterium tuberculosis is protected by an unusual and highly impermeable cell
      envelope that is critically important for the successful colonization of the
      host. The outermost surface of this cell envelope is formed by capsular
      polysaccharides that play an important role in modulating the initial
      interactions once the bacillus enters the body. Although the bioenzymatic steps
      involved in the production of the capsular polysaccharides are emerging,
      information regarding the ability of the bacterium to modulate the composition of
      the capsule is still unknown. Here, we study the mechanisms involved in
      regulation of mycobacterial capsule biosynthesis using a high throughput screen
      for gene products involved in capsular alpha-glucan production. Utilizing this
      approach we identified a group of mutants that all carried mutations in the ATP
      binding cassette phosphate transport locus pst These mutants collectively
      exhibited a strong overproduction of capsular polysaccharides, including alpha
      glucan and arabinomannan, suggestive of a role for inorganic phosphate (Pi)
      metabolism in modulating capsular polysaccharide production. These findings were
      corroborated by the observation that growth under low Pi conditions as well as
      chemical activation of the stringent response induces capsule production in a
      number of mycobacterial species. This induction is, in part, dependent on sigma
      factor E. Finally, we show that Mycobacterium marinum, a model organism for M.
      tuberculosis, encounters Pi stress during infection, which shows the relevance of
      our findings in vivo.

PMID- 27044744
TI  - The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by Inhibiting
      Chemokine/Glycosaminoglycan Interactions.
AB  - TNF-stimulated gene-6 (TSG-6) is a multifunctional protein secreted in response
      to pro-inflammatory stimuli by a wide range of cells, including neutrophils,
      monocytes, and endothelial cells. It has been shown to mediate anti-inflammatory
      and protective effects when administered in disease models, in part, by reducing
      neutrophil infiltration. Human TSG-6 inhibits neutrophil migration by binding
      CXCL8 through its Link module (Link_TSG6) and interfering with the presentation
      of CXCL8 on cell-surface glycosaminoglycans (GAGs), an interaction that is vital
      for the function of many chemokines. TSG-6 was also found to interact with
      chemokines CXCL11 and CCL5, suggesting the possibility that it may function as a
      broad specificity chemokine-binding protein, functionally similar to those
      encoded by viruses. This study was therefore undertaken to explore the ability of
      TSG-6 to regulate the function of other chemokines. Herein, we demonstrate that
      Link_TSG6 binds chemokines from both the CXC and CC families, including CXCL4,
      CXCL12, CCL2, CCL5, CCL7, CCL19, CCL21, and CCL27. We also show that the
      Link_TSG6-binding sites on chemokines overlap with chemokine GAG-binding sites,
      and that the affinities of Link_TSG6 for these chemokines (KD values 1-85 nm)
      broadly correlate with chemokine-GAG affinities. Link_TSG6 also inhibits
      chemokine presentation on endothelial cells not only through a direct interaction
      with chemokines but also by binding and therefore masking the availability of
      GAGs. Along with previous work, these findings suggest that TSG-6 functions as a
      pluripotent regulator of chemokines by modulating chemokine/GAG interactions,
      which may be a major mechanism by which TSG-6 produces its anti-inflammatory
      effects in vivo.

PMID- 27044745
TI  - PLEKHA7 Recruits PDZD11 to Adherens Junctions to Stabilize Nectins.
AB  - PLEKHA7 is a junctional protein implicated in stabilization of the cadherin
      protein complex, hypertension, cardiac contractility, glaucoma, microRNA
      processing, and susceptibility to bacterial toxins. To gain insight into the
      molecular basis for the functions of PLEKHA7, we looked for new PLEKHA7
      interactors. Here, we report the identification of PDZ domain-containing protein
      11 (PDZD11) as a new interactor of PLEKHA7 by yeast two-hybrid screening and by
      mass spectrometry analysis of PLEKHA7 immunoprecipitates. We show that PDZD11 (17
      kDa) is expressed in epithelial and endothelial cells, where it forms a complex
      with PLEKHA7, as determined by co-immunoprecipitation analysis. The N-terminal
      Trp-Trp (WW) domain of PLEKHA7 interacts directly with the N-terminal 44 amino
      acids of PDZD11, as shown by GST-pulldown assays. Immunofluorescence analysis
      shows that PDZD11 is localized at adherens junctions in a PLEKHA7-dependent
      manner, because its junctional localization is abolished by knock-out of PLEKHA7,
      and is rescued by re-expression of exogenous PLEKHA7. The junctional recruitment
      of nectin-1 and nectin-3 and their protein levels are decreased via proteasome
      mediated degradation in epithelial cells where either PDZD11 or PLEKHA7 have been
      knocked-out. PDZD11 forms a complex with nectin-1 and nectin-3, and its PDZ
      domain interacts directly with the PDZ-binding motif of nectin-1. PDZD11 is
      required for the efficient assembly of apical junctions of epithelial cells at
      early time points in the calcium-switch model. These results show that the
      PLEKHA7-PDZD11 complex stabilizes nectins to promote efficient early junction
      assembly and uncover a new molecular mechanism through which PLEKHA7 recruits PDZ
      binding membrane proteins to epithelial adherens junctions. 

PMID- 27044746
TI  - Regulation of Cancer Cell Behavior by the Small GTPase Rab13.
AB  - The members of the Rab family of GTPases are master regulators of cellular
      membrane trafficking. With ~70 members in humans, Rabs have been implicated in
      all steps of membrane trafficking ranging from vesicle formation and transport to
      vesicle docking/tethering and fusion. Vesicle trafficking controls the
      localization and levels of a myriad of proteins, thus regulating cellular
      functions including proliferation, metabolism, cell-cell adhesion, and cell
      migration. It is therefore not surprising that impairment of Rab pathways is
      associated with diseases including cancer. In this review, we highlight evidence
      supporting the role of Rab13 as a potent driver of cancer progression. 

PMID- 27044747
TI  - Ubiquitin D Regulates IRE1alpha/c-Jun N-terminal Kinase (JNK) Protein-dependent
      Apoptosis in Pancreatic Beta Cells.
AB  - Pro-inflammatory cytokines contribute to pancreatic beta cell apoptosis in type 1
      diabetes at least in part by inducing endoplasmic reticulum (ER) stress and the
      consequent unfolded protein response (UPR). It remains to be determined what
      causes the transition from "physiological" to "apoptotic" UPR, but accumulating
      evidence indicates that signaling by the ER transmembrane protein IRE1alpha is
      critical for this transition. IRE1alpha activation is regulated by both intra-ER
      and cytosolic cues. We evaluated the role for the presently discovered cytokine
      induced and IRE1alpha-interacting protein ubiquitin D (UBD) on the regulation of
      IRE1alpha and its downstream targets. UBD was identified by use of a MAPPIT
      (mammalian protein-protein interaction trap)-based IRE1alpha interactome screen
      followed by comparison against functional genomic analysis of human and rodent
      beta cells exposed to pro-inflammatory cytokines. Knockdown of UBD in human and
      rodent beta cells and detailed signal transduction studies indicated that UBD
      modulates cytokine-induced UPR/IRE1alpha activation and apoptosis. UBD expression
      is induced by the pro-inflammatory cytokines interleukin (IL)-1beta and
      interferon (IFN)-gamma in rat and human pancreatic beta cells, and it is also up
      regulated in beta cells of inflamed islets from non-obese diabetic mice. UBD
      interacts with IRE1alpha in human and rodent beta cells, modulating IRE1alpha
      dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that
      UBD provides a negative feedback on cytokine-induced activation of the
      IRE1alpha/JNK pro-apoptotic pathway in cytokine-exposed beta cells.

PMID- 27044748
TI  - Hematopoietic and Leukemic Stem Cells Have Distinct Dependence on Tcf1 and Lef1
      Transcription Factors.
AB  - Hematopoietic and leukemic stem cells (HSCs and LSCs) have self-renewal ability
      to maintain normal hematopoiesis and leukemia propagation, respectively. Tcf1 and
      Lef1 transcription factors are expressed in HSCs, and targeting both factors
      modestly expanded the size of the HSC pool due to diminished HSC quiescence.
      Functional defects of Tcf1/Lef1-deficient HSCs in multi-lineage blood
      reconstitution was only evident under competitive conditions or when subjected to
      repeated regenerative stress. These are mechanistically due to direct positive
      regulation of Egr and Tcf3 by Tcf1 and Lef1, and significantly, forced expression
      of Egr1 in Tcf1/Lef1-deficient HSCs restored HSC quiescence. In a preclinical CML
      model, loss of Tcf1/Lef1 did not show strong impact on leukemia initiation and
      progression. However, when transplanted into secondary recipients, Tcf1/Lef1
      deficient LSCs failed to propagate CML. By induced deletion of Tcf1 and Lef1 in
      pre-established CML, we further demonstrated an intrinsic requirement for these
      factors in LSC self-renewal. When combined with imatinib therapy, genetic
      targeting of Tcf1 and Lef1 potently diminished LSCs and conferred better
      protection to the CML recipients. LSCs are therefore more sensitive to loss of
      Tcf1 and Lef1 than HSCs in their self-renewal capacity. The differential
      requirements in HSCs and LSCs thus identify Tcf1 and Lef1 transcription factors
      as novel therapeutic targets in treating hematological malignancies, and
      inhibition of Tcf1/Lef1-regulated transcriptional programs may thus provide a
      therapeutic window to eliminate LSCs with minimal side effect on normal HSC
      functions. 

PMID- 27044749
TI  - Hypercapnia Suppresses the HIF-dependent Adaptive Response to Hypoxia.
AB  - Molecular oxygen and carbon dioxide are the primary gaseous substrate and product
      of oxidative metabolism, respectively. Hypoxia (low oxygen) and hypercapnia (high
      carbon dioxide) are co-incidental features of the tissue microenvironment in a
      range of pathophysiologic states, including acute and chronic respiratory
      diseases. The hypoxia-inducible factor (HIF) is the master regulator of the
      transcriptional response to hypoxia; however, little is known about the impact of
      hypercapnia on gene transcription. Because of the relationship between hypoxia
      and hypercapnia, we investigated the effect of hypercapnia on the HIF pathway.
      Hypercapnia suppressed HIF-alpha protein stability and HIF target gene expression
      both in mice and cultured cells in a manner that was at least in part independent
      of the canonical O2-dependent HIF degradation pathway. The suppressive effects of
      hypercapnia on HIF-alpha protein stability could be mimicked by reducing
      intracellular pH at a constant level of partial pressure of CO2 Bafilomycin A1, a
      specific inhibitor of vacuolar-type H(+)-ATPase that blocks lysosomal
      degradation, prevented the hypercapnic suppression of HIF-alpha protein. Based on
      these results, we hypothesize that hypercapnia counter-regulates activation of
      the HIF pathway by reducing intracellular pH and promoting lysosomal degradation
      of HIF-alpha subunits. Therefore, hypercapnia may play a key role in the
      pathophysiology of diseases where HIF is implicated.

PMID- 27044750
TI  - Inhibition of MMP-9-dependent Degradation of Gelatin, but Not Other MMP-9
      Substrates, by the MMP-9 Hemopexin Domain Blades 1 and 4.
AB  - Degradation and remodeling of the extracellular matrix by matrix
      metalloproteinases (MMPs) plays important roles in normal development,
      inflammation, and cancer. MMP-9 efficiently degrades the extracellular matrix
      component gelatin, and the hemopexin domain of MMP-9 (PEX9) inhibits this
      degradation. To study the molecular basis of this inhibition, we generated GST
      fusion proteins containing PEX9 or truncated forms corresponding to specific
      structural blades (B1-B4) of PEX9. GST-PEX9 inhibited MMP-9-driven gelatin
      proteolysis, measured by gelatin zymography, FITC-gelatin conversion, and DQ
      gelatin degradation assays. However, GST-PEX9 did not prevent the degradation of
      other MMP-9 substrates, such as a fluorogenic peptide, alphaB crystalline, or
      nonmuscular actin. Therefore, PEX9 may inhibit gelatin degradation by shielding
      gelatin and specifically preventing its binding to MMP-9. Accordingly, GST-PEX9
      also abolished the degradation of gelatin by MMP-2, confirming that PEX9 is not
      an MMP-9 antagonist. Moreover, GST-B4 and, to a lesser extent, GST-B1 also
      inhibited gelatin degradation by MMP-9, indicating that these regions are
      responsible for the inhibitory activity of PEX9. Accordingly, ELISAs demonstrated
      that GST-B4 and GST-B1 specifically bound to gelatin. Our results establish new
      functions of PEX9 attributed to blades B4 and B1 and should help in designing
      specific inhibitors of gelatin degradation.

PMID- 27044751
TI  - DNA Interactions Probed by Hydrogen-Deuterium Exchange (HDX) Fourier Transform
      Ion Cyclotron Resonance Mass Spectrometry Confirm External Binding Sites on the
      Minichromosomal Maintenance (MCM) Helicase.
AB  - The archaeal minichromosomal maintenance (MCM) helicase from Sulfolobus
      solfataricus (SsoMCM) is a model for understanding structural and mechanistic
      aspects of DNA unwinding. Although interactions of the encircled DNA strand
      within the central channel provide an accepted mode for translocation,
      interactions with the excluded strand on the exterior surface have mostly been
      ignored with regard to DNA unwinding. We have previously proposed an extension of
      the traditional steric exclusion model of unwinding to also include significant
      contributions with the excluded strand during unwinding, termed steric exclusion
      and wrapping (SEW). The SEW model hypothesizes that the displaced single strand
      tracks along paths on the exterior surface of hexameric helicases to protect
      single-stranded DNA (ssDNA) and stabilize the complex in a forward unwinding
      mode. Using hydrogen/deuterium exchange monitored by Fourier transform ion
      cyclotron resonance MS, we have probed the binding sites for ssDNA, using
      multiple substrates targeting both the encircled and excluded strand
      interactions. In each experiment, we have obtained >98.7% sequence coverage of
      SsoMCM from >650 peptides (5-30 residues in length) and are able to identify
      interacting residues on both the interior and exterior of SsoMCM. Based on
      identified contacts, positively charged residues within the external waist region
      were mutated and shown to generally lower DNA unwinding without negatively
      affecting the ATP hydrolysis. The combined data globally identify binding sites
      for ssDNA during SsoMCM unwinding as well as validating the importance of the SEW
      model for hexameric helicase unwinding.

PMID- 27044752
TI  - Molecular Mechanism of Regulation of MTA1 Expression by Granulocyte Colony
      stimulating Factor.
AB  - Parkinson disease (PD) is a neurodegenerative disorder with loss of dopaminergic
      neurons of the brain, which results in insufficient synthesis and action of
      dopamine. Metastasis-associated protein 1 (MTA1) is an upstream modulator of
      tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, and
      hence MTA1 plays a significant role in PD pathogenesis. To impart functional and
      clinical significance to MTA1, we analyzed MTA1 and TH levels in the substantia
      nigra region of a large cohort of human brain tissue samples by Western blotting,
      quantitative PCR, and immunohistochemistry. Our results showed that MTA1 and TH
      levels were significantly down-regulated in PD samples as compared with normal
      brain tissue. Correspondingly, immunohistochemistry analysis for MTA1 in
      substantia nigra sections revealed that 74.1% of the samples had a staining
      intensity of <6 in the PD samples as compared with controls, 25.9%, with an odds
      ratio of 8.54. Because of the clinical importance of MTA1 established in PD, we
      looked at agents to modulate MTA1 expression in neuronal cells, and granulocyte
      colony-stimulating factor (G-CSF) was chosen, due to its clinically proven
      neurogenic effects. Treatment of the human neuronal cell line KELLY and acute 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model with G-CSF showed
      significant induction of MTA1 and TH with rescue of phenotype in the mouse model.
      Interestingly, the observed induction of TH was compromised on silencing of MTA1.
      The underlying molecular mechanism of MTA1 induction by G-CSF was proved to be
      through induction of c-Fos and its recruitment to the MTA1 promoter.

PMID- 27044753
TI  - Microtubule bundling plays a role in ethylene-mediated cortical microtubule
      reorientation in etiolated Arabidopsis hypocotyls.
AB  - The gaseous hormone ethylene is known to regulate plant growth under etiolated
      conditions (the 'triple response'). Although organization of cortical
      microtubules is essential for cell elongation, the underlying mechanisms that
      regulate microtubule organization by hormone signaling, including ethylene, are
      ambiguous. In the present study, we demonstrate that ethylene signaling
      participates in regulation of cortical microtubule reorientation. In particular,
      regulation of microtubule bundling is important for this process in etiolated
      hypocotyls. Time-lapse analysis indicated that selective stabilization of
      microtubule-bundling structures formed in various arrays is related to ethylene
      mediated microtubule orientation. Bundling events and bundle growth lifetimes
      were significantly increased in oblique and longitudinal arrays, but decreased in
      transverse arrays in wild-type cells in response to ethylene. However, the
      effects of ethylene on microtubule bundling were partially suppressed in a
      microtubule-bundling protein WDL5 knockout mutant (wdl5-1). This study suggests
      that modulation of microtubule bundles that have formed in certain orientations
      plays a role in reorienting microtubule arrays in response to ethylene-mediated
      etiolated hypocotyl cell elongation.

PMID- 27044754
TI  - FRMD4A-cytohesin signaling modulates the cellular release of tau.
AB  - One of the defining pathological features of Alzheimer's disease is the
      intraneuronal accumulation of tau (also known as MAPT) protein. Tau is also
      secreted from neurons in response to various stimuli and accumulates in the
      cerebrospinal fluid of Alzheimer's disease patients. Tau pathology might spread
      from cell to cell through a mechanism involving secretion and uptake. Here, we
      developed an assay to follow cellular release and uptake of tau dimers.
      Individual silencing of ten common late-onset Alzheimer's disease risk genes in
      HEK293T cells expressing the tau reporters suggested that FRMD4A is functionally
      linked to tau secretion. FRMD4A depletion by using RNA interference (RNAi)
      reduced and overexpression increased tau secretion. The activity of cytohesins,
      interactors of FRMD4A and guanine-nucleotide-exchange factors of Arf6, was
      necessary for FRMD4A-induced tau secretion. Increased Arf6 and cell polarity
      signaling through Par6 and atypical protein kinase Czeta (aPKCzeta) stimulated
      tau secretion. In mature cortical neurons, FRMD4A RNAi or inhibition of
      cytohesins strongly upregulated secretion of endogenous tau. These results
      suggest that FRMD4A, a genetic risk factor for late-onset Alzheimer's disease,
      regulates tau secretion by activating cytohesin-Arf6 signaling. We conclude that
      genetic risk factors of Alzheimer's disease might modulate disease progression by
      altering tau secretion.

PMID- 27044755
TI  - Vimentin filaments regulate integrin-ligand interactions by binding to the
      cytoplasmic tail of integrin beta3.
AB  - Vimentin, an intermediate filament protein induced during epithelial-to
      mesenchymal transition, is known to regulate cell migration and invasion.
      However, it is still unclear how vimentin controls such behaviors. In this study,
      we aimed to find a new integrin regulator by investigating the H-Ras-mediated
      integrin suppression mechanism. Through a proteomic screen using the integrin
      beta3 cytoplasmic tail protein, we found that vimentin might work as an effector
      of H-Ras signaling. H-Ras converted filamentous vimentin into aggregates near the
      nucleus, where no integrin binding can occur. In addition, an increase in the
      amount of vimentin filaments accessible to the integrin beta3 tail enhanced talin
      induced integrin binding to its ligands by inducing integrin clustering. In
      contrast, the vimentin head domain, which was found to bind directly to the
      integrin beta3 tail and compete with endogenous vimentin filaments for integrin
      binding, induced nuclear accumulation of vimentin filaments and reduced the
      amount of integrin-ligand binding. Finally, we found that expression of the
      vimentin head domain can reduce cell migration and metastasis. From these data,
      we suggest that filamentous vimentin underneath the plasma membrane is involved
      in increasing integrin adhesiveness, and thus regulation of the vimentin-integrin
      interaction might control cell adhesion.

PMID- 27044756
TI  - Two classes of short intraflagellar transport train with different 3D structures
      are present in Chlamydomonas flagella.
AB  - Intraflagellar transport (IFT) is responsible for the bidirectional trafficking
      of molecular components required for the elongation and maintenance of eukaryotic
      cilia and flagella. Cargo is transported by IFT 'trains', linear rows of
      multiprotein particles moved by molecular motors along the axonemal doublets. We
      have previously described two structurally distinct categories of 'long' and
      'short' trains. Here, we analyse the relative number of these trains throughout
      flagellar regeneration and show that long trains are most abundant at the
      beginning of flagellar growth whereas short trains gradually increase in number
      as flagella elongate. These observations are incompatible with the previous
      hypothesis that short trains are derived solely from the reorganization of long
      trains at the flagellar tip. We demonstrate with electron tomography the
      existence of two distinct ultrastructural organizations for the short trains, we
      name these 'narrow' and 'wide', and provide the first 3D model of the narrow
      short trains. These trains are characterized by tri-lobed units, which repeat
      longitudinally every 16 nm and contact protofilament 7 of the B-tubule.
      Functional implications of the new structural evidence are discussed.

PMID- 27044757
TI  - Mapping growth-factor-modulated Akt signaling dynamics.
AB  - Growth factors alter cellular behavior through shared signaling cascades, raising
      the question of how specificity is achieved. Here, we have determined how growth
      factor actions are encoded into Akt signaling dynamics by real-time tracking of a
      fluorescent sensor. In individual cells, Akt activity was encoded in an analog
      pattern, with similar latencies (~2 min) and half-maximal peak response times
      (range of 5-8 min). Yet, different growth factors promoted dose-dependent and
      heterogeneous changes in signaling dynamics. Insulin treatment caused sustained
      Akt activity, whereas EGF or PDGF-AA promoted transient signaling; PDGF-BB
      produced sustained responses at higher concentrations, but short-term effects at
      low doses, actions that were independent of the PDGF-alpha receptor. Transient
      responses to EGF were caused by negative feedback at the receptor level, as a
      second treatment yielded minimal responses, whereas parallel exposure to IGF-I
      caused full Akt activation. Small-molecule inhibitors reduced PDGF-BB signaling
      to transient responses, but only decreased the magnitude of IGF-I actions. Our
      observations reveal distinctions among growth factors that use shared components,
      and allow us to capture the consequences of receptor-specific regulatory
      mechanisms on Akt signaling.

PMID- 27044758
TI  - Rheumatoid arthritis: Sclerostin: a novel role in TNF arthritis?

PMID- 27044759
TI  - Genetics: Novel insights from large cross-disease study.

PMID- 27044760
TI  - Acute-on-chronic liver failure: a new syndrome in cirrhosis.
AB  - Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and
      also have organ failure(s) are at high risk of short-term death. These patients
      have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now
      considered as a new syndrome that it is distinct from "mere" AD not only because
      of the presence of organ failure(s) and high short-term mortality but also
      because of younger age, higher prevalence of alcoholic etiology of cirrhosis,
      higher prevalence of some precipitants (such as bacterial infections, active
      alcoholism), and more intense systemic inflammatory response. ACLF is a new
      syndrome also because severe sepsis or severe alcoholic hepatitis do not account
      for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown"
      origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of
      "unknown origin" are subcategories of the syndrome. 

PMID- 27044761
TI  - A concise review of updated guidelines regarding the management of hepatocellular
      carcinoma around the world: 2010-2016.
AB  - Many guidelines for hepatocellular carcinoma (HCC) have been published and
      updated globally. In contrast to other cancers, there is a range of treatment
      options for HCC involving several multidisciplinary care of the patient.
      Consequently, enormous heterogeneity in management trends has been observed. To
      support standard care for HCC, we systematically appraised 8 current guidelines
      for HCC around the world, including 3 guidelines from Asia, 2 from Europe, and 3
      from the United States according to the selection criteria of credibility
      influence and multi-faceted. After a systematic appraisal, we found that these
      guidelines have both similarities and dissimilarities in terms of surveillance
      and treatment allocation recommendations due to regional differences in disease
      and other variables (diagnosis, staging systems) secondary to the lack of a
      solid, high level of evidence. In contrast to other tumors, the geographic
      differences in tumor biology (i.e., areas of increased hepatitis B prevalence)
      and available resources (organ availability for transplantation, medical
      technology, accessibility to treatment, health systems, and health resources)
      make it impractical to have an internationally universal guideline for all
      patients with HCC. Although Barcelona-Clinic Liver Cancer (BCLC) has long been
      dominant system for treatment-guiding staging of HCC, many Asia-pacific experts
      do not fully agree with its principle. The concepts of BCLC, for surgical
      resection or other locoregional therapy, are considered too conservative. Asian
      guidelines represent consensus about surgical resection and TACE indication for
      more advanced tumor. 

PMID- 27044764
TI  - Magnetization-tagged MRI is a simple method for predicting liver fibrosis.
AB  - BACKGROUND/AIMS: To assess the usefulness of magnetization-tagged magnetic
      resonance imaging (MRI) in quantifying cardiac-induced liver motion and
      deformation in order to predict liver fibrosis. METHODS: This retrospective study
      included 85 patients who underwent liver MRI including magnetization-tagged
      sequences from April 2010 to August 2010. Tagged images were acquired in three
      coronal and three sagittal planes encompassing both the liver and heart. A Gabor
      filter bank was used to measure the maximum value of displacement (MaxDisp) and
      the maximum and minimum values of principal strains (MaxP1 and MinP2,
      respectively). Patients were divided into three groups (no fibrosis, mild-to
      moderate fibrosis, and significant fibrosis) based on their aspartate
      aminotransferase-to-platelet ratio index (APRI) score. Group comparisons were
      made using ANOVA tests. RESULTS: The patients were divided into three groups
      according to APRI scores: no fibrosis (<= 0.5; n=41), moderate fibrosis (0.5-1.5;
      n=23), and significant fibrosis (>1.5; n=21). The values of MaxDisp were 2.9 +/-
      0.9 (mean +/- SD), 2.3 +/- 0.7, and 2.1 +/- 0.6 in the no fibrosis, moderate
      fibrosis, and significant fibrosis groups, respectively (P<0.001); the
      corresponding values of MaxP1 were 0.05 +/- 0.2, 0.04 +/- 0.02, and 0.03 +/-
      0.01, respectively (P=0.002), while those of MinP2 were -0.07 +/- 0.02, -0.05 +/-
      0.02, and -0.04 +/- 0.01, respectively (P<0.001). CONCLUSIONS: Tagge d MRI to
      quantify cardiac-induced liver motion can be easily incorporated in routine liver
      MRI and may represent a helpful complementary tool in the diagnosis of early
      liver fibrosis.

PMID- 27044765
TI  - The serum vitamin D level is inversely correlated with nonalcoholic fatty liver
      disease.
AB  - BACKGROUND/AIMS: A low vitamin D level has been associated with metabolic
      syndrome and diabetes. However, an association between a low vitamin D level and
      nonalcoholic fatty liver disease (NAFLD) has not yet been definitively
      established. This study aimed to characterize the relationship between a vitamin
      D level and NAFLD in Korea. METHODS: A cross-sectional study involving 6,055
      health check-up subjects was conducted. NAFLD was diagnosed on the basis of
      typical ultrasonographic findings and a history of alcohol consumption. RESULTS:
      The subjects were aged 51.7 +/- 10.3 years (mean +/- SD) and 54.7% were female.
      NAFLD showed a significant inverse correlation with the vitamin D level after
      adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval
      (CI)=0.75-0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily
      with increasing vitamin D level [OR=0.74, 95% CI=0.60-0.90, lowest quintile
      (<=14.4 ng/mL) vs highest quintile (>=28.9 ng/mL), p for trend <0.001].
      Multivariate regression analysis after adjusting for other metabolic factors
      revealed that NAFLD showed a significant inverse correlation with both the
      vitamin D level (>20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the
      vitamin D level in a dose-dependent manner (p for trend=0.001). CONCLUSIONS: The
      serum level of vitamin D, even when within the normal range, was found to be
      inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found
      to be inversely correlated with NAFLD independent of known metabolic risk
      factors. These findings suggest that vitamin D exerts protective effects against
      NAFLD.

PMID- 27044766
TI  - Comparison of tenofovir plus lamivudine versus tenofovir monotherapy in patients
      with lamivudine-resistant chronic hepatitis B.
AB  - BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) exhibits similar antiviral
      efficacy against treatment-naive and lamivudine (LAM)-resistant chronic hepatitis
      B (CHB). However, there are few clinical reports on the antiviral effects of TDF
      LAM combination therapy compared to TDF monotherapy in patients with LAM
      resistant CHB. METHODS: We investigated the antiviral efficacy of TDF monotherapy
      vs. TDF-LAM combination therapy in 103 patients with LAM-resistant CHB. RESULTS:
      The study subjects were treated with TDF alone (n=40) or TDF-LAM combination
      therapy (n=63) for >=6 months. The patients had previously been treated with TDF
      based rescue therapy for a median of 30.0 months (range, 8-36 months). A
      virologic response (VR) was achieved in 99 patients (96.1%): 95.0% (38/40) of
      patients in the TDF monotherapy group and 96.8% (61/63) of patients in the TDF
      LAM combination therapy group. The VR rates were not significantly different
      between the TDF monotherapy and TDF-LAM combination therapy groups (88.9 vs.
      87.3% at month 12, and 94.4 vs. 93.7% at month 24, log-rank p=0.652). Univariate
      and multivariate analyses revealed that none of the pretreatment factors were
      significantly associated with VR. CONCLUSIONS: TDF monotherapy was as effective
      as TDF-LAM combination therapy for maintaining viral suppression in the vast
      majority of patients with LAM-resistant CHB, which suggests that TDF add-on
      therapy with LAM is unnecessary.

PMID- 27044763
TI  - KASL clinical practice guidelines: management of hepatitis C.

PMID- 27044767
TI  - Survival outcomes of hepatic resection compared with transarterial
      chemoembolization or sorafenib for hepatocellular carcinoma with portal vein
      tumor thrombosis.
AB  - BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor
      thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic
      resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as
      treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT
      between January 2000 and December 2011 who received treatment with sorafenib, HR,
      or TACE were included. Patients with main PVTT, superior mesenteric vein tumor
      thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of
      172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment
      were performed is 40, 80, and 52 patients respectively. PVTT was classified as
      either involving the segmental branch (type I) or extending to involve the right
      or left portal vein (type II). RESULTS: The median survival time was
      significantly longer in the HR group (19.9 months) than in the TACE and sorafenib
      groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ
      significantly between the latter two groups (p=0.698). Among patients with CTP
      class A, type I PVTT or unilobar-involved HCC, the median survival time was
      longer in the HR group than in the TACE and sorafenib groups (p=0.006). In
      univariate analyses, the initial treatment method, tumor size, PVTT type,
      involved lobe, CTP class, and presence of cirrhosis or ascites were correlated
      with overall survival. The significant prognostic factors for overall survival in
      Cox proportional-hazards regression analysis were initial treatment method (HR
      vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262,
      p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard
      ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS:
      Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC
      in cases of CTP class A, type I PVTT or unilobar-involved HCC.

PMID- 27044768
TI  - Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in
      chronic hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and
      hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG
      IFN-alpha) and ribavirin (RBV) is a current standard treatment for chronic HCV
      infection in Korea, which has considerable adverse effects. Acute pancreatitis is
      a rare complication of PEG-IFN-alpha administration. We report a case of a 62
      year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-alpha
      2a and RBV combination therapy for chronic HCV infection. The main cause of the
      acute pancreatitis in this case was probably PEG-IFN-alpha rather than RBV for
      several reasons. A few cases have been reported in which acute pancreatitis
      occurred during treatment with PEG-IFN-alpha-2b. This is the first report of
      acute pancreatitis associated with PEG-IFN-alpha-2a in Korea. 

PMID- 27044762
TI  - KASL clinical practice guidelines: management of chronic hepatitis B.

PMID- 27044769
TI  - Portal biliopathy treated with endoscopic biliary stenting.
AB  - Portal biliopathy is defined as abnormalities in the extra- and intrahepatic
      ducts and gallbladder of patients with portal hypertension. This condition is
      associated with extrahepatic venous obstruction and dilatation of the venous
      plexus of the common bile duct, resulting in mural irregularities and compression
      of the biliary tree. Most patients with portal biliopathy remain asymptomatic,
      but approximately 10% of them advance to symptomatic abdominal pain, jaundice,
      and fever. Magnetic resonance cholangiopancreatography and endoscopic retrograde
      cholangiopancreatography are currently used as diagnostic tools because they are
      noninvasive and can be used to assess the regularity, length, and degree of bile
      duct narrowing. Management of portal biliopathy is aimed at biliary decompression
      and reducing the portal pressure. Portal biliopathy has rarely been reported in
      Korea. We present a symptomatic case of portal biliopathy that was complicated by
      cholangitis and successfully treated with biliary endoscopic procedures. 

PMID- 27044770
TI  - Primary squamous cell carcinoma of the liver: a case report.
AB  - Primary squamous cell carcinoma (SCC) of the liver is very rare, and few cases
      have been reported in Korea. Primary SCC of the liver is known to be associated
      with hepatic cysts and intrahepatic stones. A 71-year-old male was admitted to
      our hospital, and a abdominal computed tomography scan revealed a 10 * 6 cm mass
      in the liver. Analysis of a biopsy sample suggested SCC, and so our team
      performed a thorough workup to find the primary lesion, which was revealed
      hepatoma as a pure primary SCC of the liver with multiple distant metastases. The
      patient was treated with one cycle of radiotherapy, transferred to another
      hospital for hospice care, and then died 1 month after discharge. 

PMID- 27044771
TI  - Regression of esophageal varices during entecavir treatment in patients with
      hepatitis-B-virus-related liver cirrhosis.
AB  - Recent studies suggest that liver cirrhosis is reversible after administering
      oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV)
      infection. However, few studies have addressed whether esophageal varices can
      regress after such therapy. We report a case of complete regression of esophageal
      varices during entecavir therapy in patients with HBV-related liver cirrhosis,
      suggesting that complications of liver cirrhosis such as esophageal varices can
      regress after the long-term suppression of HBV replication. 

PMID- 27044772
TI  - Liver metastasis of meningeal hemangiopericytoma: a study of 5 cases.
AB  - Mesenchymal tumors in the liver, whether primary or metastatic, are rare.
      Meningeal hemangiopericytoma (HPC) is characteristically associated with delayed
      metastasis and the liver is one of the most common sites. Despite its consistent
      histological features, a pathological diagnosis of HPC in the liver is sometimes
      not straightforward due to its rarity and usually remote medical history of the
      primary meningeal tumor. In this report, the clinicopathological features of 5
      cases of metastatic HPC to the liver were reviewed and described. 

PMID- 27044773
TI  - Intraductal malignant tumors in the liver mimicking cholangiocarcinoma: Imaging
      features for differential diagnosis.

PMID- 27044778
TI  - Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with
      myocardial infarction.
AB  - Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive
      heart failure. Obese-insulin resistance increases risks of MI and heart failure.
      Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert
      cardioprotection, its effects on adverse remodeling after MI in obese-insulin
      resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse
      left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant
      rats with MI. Rats were fed either normal diet (ND) or high-fat diet (HFD) for 12
      weeks to induce obese-insulin resistance, followed by left anterior descending
      coronary artery ligation to induce MI. Then, rats in each dietary group were
      divided into five subgroups to receive vehicle, enalapril (10mg/kg/day),
      metformin (30mg/kg/day), DPP4 inhibitor vildagliptin (3mg/kg/day), or combined
      metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV
      function, pathological and biochemical studies for LV remodeling, and
      cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe
      insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than
      ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant
      rats. Although all drugs improved insulin resistance, HRV, LV function as well as
      reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced
      cardiomyocyte cross-sectional areas more than enalapril and was related to
      markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither
      improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and
      transforming growth factor-beta expression were not different among groups. In
      obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts
      better cardioprotection than enalapril in attenuating adverse LV remodeling.

PMID- 27044779
TI  - Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose
      tissue of piglets.
AB  - MicroRNAs (miRNAs) are a class of molecular posttranscriptional regulators found
      to participate in numerous biological mechanisms, such as adipogenesis, fat
      deposition, or glucose metabolism. Additionally, a detailed analysis on the
      molecular and cellular mechanisms of miRNA-related effects on metabolism leads to
      developing novel diagnostic markers and therapeutic approaches. To identify miRNA
      whose activity changed in epicardial adipose tissue in piglets during
      hyperglycemia, we analyzed the different miRNA expression patterns between
      control and hyperglycemia groups. The microarray analysis selected three
      differentially expressed microRNAs as potential biomarkers: hsa-miR-675-5p, ssc
      miR-193a-3p, and hsa-miR-144-3p. The validation of miRNA expression with real
      time PCR indicated an increased expression levels of ssc-miR-193a-3p and miR-675
      5p, whereas the expression level of hsa-miR-144-3p was lower in epicardial
      adipose tissue in response to hyperglycemia (P<0.01). The Kyoto Encyclopedia of
      Genes and Genomes (KEGG) pathway analyses suggested that these miRNAs
      differentially expressed between hyperglycemic and control piglets are involved
      in insulin, adipocytokine, and phosphatidylinositol 3-kinase-Akt signaling
      pathways, and development of type 2 diabetes as well. The results suggested that
      hyperglycemia can significantly affect the expression patterns of miRNA in
      porcine adipose tissue.

PMID- 27044780
TI  - Medical students' perception of the proposal for theme-based integrated multi
      disciplinary objective structured practical examination in Saudi Arabia.
AB  - This study aimed to find the opinion of preclinical medical students concerning a
      new suggested approach for practical assessment. Fifty-three female students
      agreed to participate in this study, out of 87 registered students in years 2 and
      3 of the basic science phase of the College of Medicine, Qassim University,
      Kingdom of Saudi Arabia. Full explanation was made to the students of theme-based
      integrated objective structured practical examination (TBI-OSPE), followed by
      distribution of a questionnaire to collect the students' opinions. The study was
      conducted in January 2015. Results showed that 78% of respondents were accepting
      of this new approach, and that only 5.7% rejected it. This difference was
      statistically significant (P<0.05). This study suggested a new model for
      assessment of preclinical students' competencies using the proposed tool (TBI
      OSPE) rather than standard classical OSPE, particularly in curricula involving
      high levels of integration and theme-based problems. This form of assessment
      would more positively enhance learning. 

PMID- 27044781
TI  - Formation of intracellular lumina in human prostate carcinoma (DU145) cells,
      maturation into signet cells, and the cribriform morphology of tumors.
AB  - The intracellular or intracytoplasmic lumen (IL) is an enigmatic histological
      structure that occurs in various tumor cells. A reassessment of diverse ILs fine
      structure micrographs obtained out of previous studies encompassing the human
      prostate carcinoma (DU145) cell line and xenotransplanted carcinomas enabled us
      to propose aspects of ILs development in cancer cells: a combination of altered
      expressions in intercellular contacts and their cytoskeletal components would
      favor a disarray of self-apical polarity orientation; those defects, associated
      with a local, entwined enriched membranous structures growing as microvilli-like
      formations out of a disrupted endoplasm and trans-Golgi sorting, create ILs in
      cells' perikarya. These misplaced intracytoplasmic domains can become enlarged
      through spaces made between the finger-like structures by accruing membranes of
      coalescent intracytoplasmic vesicles then adding microvilli and glycocalyx to
      constitute ILs. Cationic mucins added with or without a progressive or total loss
      of microvilli and content generate signet or ring cell, while ILs enlarge.
      Variable build-ups of these cells' populations in carcinomas result in
      architectural mix-up of adjacent cells around these voids, misconstrued as new
      lumen, and establish a "cribriform" tumor pattern that often implies a poor
      cancer prognosis. Alternatively, cytotoxic changes caused by anticancer pro
      oxidant treatment favor membrane alterations and exaggerate the ILs in
      xenotransplants into intracellular crypts that accompany other tumor degenerative
      changes. 

PMID- 27044783
TI  - Climate Change: A Public Health Priority.

PMID- 27044782
TI  - Randomized study of effectiveness of computerized ultrasound simulators for an
      introductory course for residents in Brazil.
AB  - PURPOSE: This study aimed to assess the impact of ultrasound simulation (SonoSim)
      on educational outcomes of an introductory point-of-care ultrasound course
      compared to hands-on training with live models alone. METHODS: Fifty-three
      internal medicine residents without ultrasound experience were randomly assigned
      to control or experimental groups. They participated in an introductory point-of
      care ultrasound course covering eight topics in eight sessions from June 23, 2014
      until July 18, 2014. Both participated in lecture and hands-on training, but
      experimental group received an hour of computerized simulator training instead of
      a second hour of hands-on training. We assessed clinical knowledge and image
      acquisition with written multiple-choice and practical exams, respectively. Of
      the 53 enrolled, 40 participants (75.5%) completed the course and all testing.
      RESULTS: For the 30-item written exam, mean score of the experimental group was
      23.1+/-3.4 (n=21) vs. 21.8+/-4.8 (n=19), (P>0 .05). For the practical exam, mean
      score for both groups was 8.7 out of 16 (P>0 .05). CONCLUSION: The substitution
      of eight hours of ultrasound simulation training for live model scanning in a 24
      hour training course did not enhance performance on written and image acquisition
      tests in an introductory ultrasound course for residents. This result suggests
      that ultrasound simulation technology used as a substitute for live model
      training on an hour-for-hour basis, did not improve learning outcomes. Further
      investigation into simulation as a total replacement for live model training will
      provide a clearer picture of the efficacy of ultrasound simulators in medical
      education.

PMID- 27044784
TI  - Global Environmental Change and Human Health.

PMID- 27044786
TI  - Changes at CMAJ.

PMID- 27044787
TI  - Changes at CMAJ.

PMID- 27044788
TI  - Changes at CMAJ.

PMID- 27044789
TI  - Changes at CMAJ.

PMID- 27044790
TI  - Changes at CMAJ.

PMID- 27044791
TI  - Minimal important difference is important.

PMID- 27044792
TI  - Legacy of international sporting events.

PMID- 27044793
TI  - The Association Between Glucose Exposure and the Risk of Peritonitis in
      Peritoneal Dialysis Patients.
AB  - ? BACKGROUND AND OBJECTIVE: Little or no clinical evidence is available on the
      association between glucose exposure and peritoneal host defense in peritoneal
      dialysis (PD) patients. The objective of the present study was to quantify the
      exposure to glucose during the first year on PD and investigate the association
      with subsequent peritonitis. ? METHODS: We analyzed prospectively collected
      demographic and peritonitis data from incident adult PD patients between 1990 and
      2010. For the present study, we conducted a review of both in- and outpatient
      medical records of all patients to obtain their day-to-day dialysis schemes
      during the first year on PD. From these data, the average exposure to glucose was
      quantified. The exposure was stratified into low- and high-glucose groups based
      on the median, analyzed per standard deviation and in quartiles. Cox proportional
      hazard models were used to calculate crude and adjusted hazard ratios (HRs) and
      95% confidence intervals for the association between glucose exposure and
      peritonitis. Adjustments were made for age, sex, primary kidney disease, diabetes
      mellitus, Davies comorbidity score and the treatment period. ? RESULTS: In total,
      230 patients were included in the study of whom 151 (66%) experienced a first
      peritonitis episode. The median follow-up time was 2.6 years (interquartile range
      [IQR]: 1.9 - 3.8) in the low-glucose group and 3.1 (IQR: 2.1 - 4.2) in the high
      glucose group. After adjustment for confounding factors, no association between
      high glucose exposure and the risk of peritonitis was found (HR: 0.81; 0.55 -
      1.17). No association was present when glucose exposure was analyzed per standard
      deviation (SD) (HR: 0.98; 0.79 - 1.21) or patient quartiles were applied. No
      association was identified between glucose exposure and severe peritonitis,
      Staphylococcus aureus peritonitis, or a peritonitis episode that lasted more than
      14 days. ? CONCLUSIONS: Exposure to glucose is not associated with an increased
      risk of peritonitis. The equilibrium between glycemic harm to peritoneal host
      defense and detrimental effects of glucose on invading microorganisms may
      determine the susceptibility to peritoneal infection.

PMID- 27044794
TI  - Estimation of the Center Effect on Early Peritoneal Dialysis Failure: A
      Multilevel Modelling Approach.
AB  - ? INTRODUCTION: This study was carried out to investigate the center effect on
      the risk of peritoneal dialysis (PD) failure within the first 6 months of therapy
      using a multilevel approach. ? METHODS: This was a retrospective cohort study
      based on data from the French Language Peritoneal Dialysis Registry. We analyzed
      5,406 incident patients starting PD between January 2008 and December 2012 in 128
      PD centers. The end of the observation period was December 31, 2013. ? RESULTS:
      Of the 5,406 patients, 415 stopped PD within the first 6 months. There was a
      significant heterogeneity between centers (variance of the random effect: 0.10).
      Only 3% of the variance of the event of interest was attributable to differences
      between centers. At the individual level, only treatment before PD (odds ratio
      [OR]: 1.93 for hemodialysis and OR: 2.29 for renal transplantation) and
      underlying nephropathy (p < 0.01) were associated with early PD failure. At the
      center level, only center experience was associated (OR: 0.78) with the risk of
      PD failure. Center effect accounted for 52% of the disparities between centers. ?
      CONCLUSION: Center effect on early PD failure is significant. Center experience
      is associated with a lower risk of transfer to hemodialysis.

PMID- 27044795
TI  - Rate of Decline of Residual Kidney Function Before and After the Start of
      Peritoneal Dialysis.
AB  - ? BACKGROUND: There is a paucity of information on whether peritoneal dialysis
      (PD) slows the decline of residual kidney function (RKF) compared to the natural
      slope of RKF decline prior to dialysis start. Our aim was to analyze the RKF
      decline before and after initiating PD, and to determine the principal factors
      affecting this decline during the PD period. ? METHODS: We determined individual
      glomerular filtration rates (GFR) for approximately 12 months before and after PD
      in 77 new PD patients in a large academic medical center (2008 - 2012). The GFR
      was estimated by the Modification of Diet in Renal Disease (MDRD) equation in the
      predialysis period and by averaging 24-hour urine creatinine and urea clearances
      in the PD period. The rate of RKF decline was calculated using unadjusted linear
      regression analysis. Wilcoxon signed rank test was used to compare RKF decline
      before and after PD initiation. Multivariate linear regression was used to
      identify independent risk factors for RKF decline in the PD phase. ? RESULTS: A
      significantly slower mean rate of RKF decline was observed in the PD period
      compared with the predialysis period (-0.21 +/- 0.30 vs -0.59 +/- 0.55
      mL/min/1.73 m(2)/month, p < 0.01). Higher baseline RKF, higher serum phosphate,
      and older age were independently associated with faster decline of RKF (all p <
      0.01). ? CONCLUSIONS: In patients with advanced chronic kidney disease,
      initiating PD was associated with a slower rate of RKF decline compared to the
      rate in the predialysis period.

PMID- 27044796
TI  - Alternating Mupirocin/Gentamicin is Associated with Increased Risk of Fungal
      Peritonitis as Compared with Gentamicin Alone - Results of a Randomized Open
      Label Controlled Trial.
AB  - ? BACKGROUND AND OBJECTIVES: Catheter-related infection, namely exit-site
      infection (ESI) and peritonitis, is a major infectious complication and remains a
      main cause of technique failure for patients receiving peritoneal dialysis (PD).
      Topical application of antibiotic cream might reduce catheter-related infection
      but emergence of resistant or opportunistic organisms could be a concern. Optimal
      topical agents and regimens remain to be determined. We did a study to examine
      the effect of an alternating topical antibiotic regimen in preventing catheter
      related infection. ? METHOD: We performed a single-center, randomized, open-label
      study to compare daily topical application of gentamicin cream with a
      gentamicin/mupirocin alternate regimen to the exit site. Patients randomized to
      alternating regimen were asked to have daily application of gentamicin cream in
      odd months and mupirocin cream in even months. Primary outcomes were ESI and
      peritonitis. Secondary outcomes were catheter removal or death caused by catheter
      related infection. A total of 146 patients (71, gentamicin group; 75, alternating
      regimen group) were enrolled with a total follow-up duration of 174 and 181
      patient-years for gentamicin and alternating groups, respectively. All patients
      were followed up until catheter removal, death, transfer to another unit,
      transplantation or the end of the study on March 31, 2014. There were no
      significant differences in the age, sex, dialysis vintage, and rate of diabetes,
      helper-assisted dialysis and methicillin-resistant Staphylococcus aureus (MRSA)
      carriage state. ? RESULTS: No difference was seen in the time to first ESI or
      peritonitis. However, the time to first gram-negative peritonitis seemed longer
      for the gentamicin group (p = 0.055). The 2 groups showed a similar rate of ESI
      (0.17/yr vs 0.19/yr, p = 0.93) but P. aeruginosa ESI was less common in the
      gentamicin group (0.06/yr vs 0.11/yr, p < 0.001). There was no difference in the
      incidence of ESI due to non-tuberculous mycobacteria. Peritonitis rate was
      significantly lower in the gentamicin group (0.22/yr vs 0.32/yr, p < 0.001), with
      a striking decrease in gram-negative peritonitis (0.08/yr vs 0.14/yr, p < 0.001),
      and fungal peritonitis (0.006/yr vs 0.03/yr, p < 0.001), which was all
      antibiotics-related episodes with antecedent use of systemic antibiotics for the
      treatment of catheter-related infections. There was no significant difference in
      the catheter loss or death related to catheter-related infection. ? CONCLUSION:
      Alternating gentamicin/mupirocin cream application appeared as effective as
      gentamicin alone in preventing ESI except for P. aeruginosa. However, it was
      inferior to gentamicin in the prevention of peritonitis episodes, especially for
      those caused by gram-negative organisms. It was also not useful in reducing
      catheter-related infection due to opportunistic organisms but instead associated
      with a higher incidence of antibiotic-related fungal peritonitis.

PMID- 27044797
TI  - Comparison of Early Mechanical and Infective Complications in First Time Blind,
      Bedside, Midline Percutaneous Tenckhoff Catheter Insertion with Ultra-Short Break
      In Period in Diabetics and Non-Diabetics: Setting New Standards.
AB  - ? BACKGROUND: There are no large studies that have examined ultra-short break-in
      period with a blind, bedside, midline approach to Tenckhoff catheter insertion. ?
      METHODS: Observational cohort study of 245 consecutive adult patients who
      underwent percutaneous catheter insertion for chronic peritoneal dialysis (PD) at
      our center from January 2009 to December 2013. There were 132 (53.9%) diabetics
      and 113 (46.1%) non-diabetics in the cohort. ? RESULTS: The mean break-in period
      for the percutaneous group was 2.68 +/- 2.6 days. There were significantly more
      males among the diabetics (103 [78%] vs 66 [58.4%], p = 0.001). Diabetics had a
      significantly higher body mass index (BMI) (23.9 +/- 3.7 kg/m2 vs 22.2 +/- 4
      kg/m2, p < 0.001) and lower serum albumin (33.1 +/- 6.3 g/L vs 37 +/- 6 g/L, p <
      0.001) compared with non-diabetics. Poor catheter outflow was present in 6 (4.5%)
      diabetics and 16 (14.2%) non-diabetics (p = 0.009). Catheter migration was also
      significantly more common in the non-diabetic group (11 [9.7%] vs 2 [1.5%], p =
      0.004). Primary catheter non-function was present in 17(15%) of the non-diabetics
      and in 7(5.3%) of the diabetics (p = 0.01). There were no mortality or major non
      procedural complications during the catheter insertions. Among patients with 1
      year of follow-up data, catheter survival (93/102 [91.2%] vs 71/82 [86.6%], p =
      0.32) and technique survival (93/102 [91.2%] vs 70/82 [85.4%], p = 0.22) at 1
      year was comparable between diabetics and non-diabetics, respectively. ?
      CONCLUSIONS: Percutaneous catheter insertion by practicing nephrologists provides
      a short break-in period with very low mechanical and infective complications. Non
      diabetic status emerged as a significant risk factor for primary catheter non
      function presumed to be due to more patients with lower BMI and thus smaller
      abdominal cavities. This is the first report that systematically compares
      diabetic and non-diabetic patients.

PMID- 27044798
TI  - Editorial overview: Emerging viruses: Interspecies transmission.

PMID- 27044799
TI  - Kidney versus Liver Specification of SLC and ABC Drug Transporters, Tight
      Junction Molecules, and Biomarkers.
AB  - The hepatocyte nuclear factors, Hnf1a and Hnf4a, in addition to playing key roles
      in determining hepatocyte fate, have been implicated as candidate lineage
      determining transcription factors in the kidney proximal tubule (PT) [Martovetsky
      et. al., (2012) Mol Pharmacol 84:808], implying an additional level of regulation
      that is potentially important in developmental and/or tissue-engineering
      contexts. Mouse embryonic fibroblasts (MEFs) transduced with Hnf1a and Hnf4a form
      tight junctions and express multiple PT drug transporters (e.g., Slc22a6/Oat1,
      Slc47a1/Mate1, Slc22a12/Urat1, Abcg2/Bcrp, Abcc2/Mrp2, Abcc4/Mrp4), nutrient
      transporters (e.g., Slc34a1/NaPi-2, Slco1a6), and tight junction proteins
      (occludin, claudin 6, ZO-1/Tjp1, ZO-2/Tjp2). In contrast, the coexpression (with
      Hnf1a and Hnf4a) of GATA binding protein 4 (Gata4), as well as the forkhead box
      transcription factors, Foxa2 and Foxa3, in MEFs not only downregulates PT markers
      but also leads to upregulation of several hepatocyte markers, including albumin,
      apolipoprotein, and transferrin. A similar result was obtained with primary mouse
      PT cells. Thus, the presence of Gata4 and Foxa2/Foxa3 appears to alter the effect
      of Hnf1a and Hnf4a by an as-yet unidentified mechanism, leading toward the
      generation of more hepatocyte-like cells as opposed to cells exhibiting PT
      characteristics. The different roles of Hnf4a in the kidney and liver was further
      supported by reanalysis of ChIP-seq data, which revealed Hnf4a colocalization in
      the kidney near PT-enriched genes compared with those genes enriched in the
      liver. These findings provide valuable insight, not only into the developmental,
      and perhaps organotypic, regulation of drug transporters, drug-metabolizing
      enzymes, and tight junctions, but also for regenerative medicine strategies aimed
      at restoring the function of the liver and/or kidney (acute kidney injury, AKI;
      chronic kidney disease, CKD).

PMID- 27044800
TI  - A New Marmoset P450 4F12 Enzyme Expressed in Small Intestines and Livers
      Efficiently Metabolizes Antihistaminic Drug Ebastine.
AB  - Common marmosets (Callithrix jacchus) are attracting attention as animal models
      in preclinical studies for drug development. However, cytochrome P450s (P450s),
      major drug-metabolizing enzymes, have not been fully identified and characterized
      in marmosets. In this study, based on the four novel P450 4F genes found on the
      marmoset genome, we successfully isolated P450 4F2, 4F3B, 4F11, and 4F12 cDNAs in
      marmoset livers. Deduced amino acid sequences of the four marmoset P450 4F forms
      exhibited high sequence identities (87%-93%) to the human and cynomolgus monkey
      P450 4F homologs. Marmoset P450 4F3B and 4F11 mRNAs were predominantly expressed
      in livers, whereas marmoset P450 4F2 and 4F12 mRNAs were highly expressed in
      small intestines and livers. Four marmoset P450 4F proteins heterologously
      expressed in Escherichia coli catalyzed the omega-hydroxylation of leukotriene B4
      In addition, marmoset P450 4F12 effectively catalyzed the hydroxylation of
      antiallergy drug ebastine, a human P450 2J/4F probe substrate. Ebastine
      hydroxylation activities by small intestine and liver microsomes from marmosets
      and cynomolgus monkeys showed greatly higher values than those of humans.
      Ebastine hydroxylation activities by marmoset and cynomolgus monkey small
      intestine microsomes were inhibited (approximately 60%) by anti-P450 4F
      antibodies, unlike human small intestine microsomes, suggesting that contribution
      of P450 4F enzymes for ebastine hydroxylation in the small intestine might be
      different between marmosets/cynomolgus monkeys and humans. These results
      indicated that marmoset P450 4F2, 4F3B, 4F11, and 4F12 were expressed in livers
      and/or small intestines and were functional in the metabolism of endogenous and
      exogenous compounds, similar to those of cynomolgus monkeys and humans.

PMID- 27044801
TI  - Time-frequency analysis of neuronal populations with instantaneous resolution
      based on noise-assisted multivariate empirical mode decomposition.
AB  - BACKGROUND: Linear analysis has classically provided powerful tools for
      understanding the behavior of neural populations, but the neuron responses to
      real-world stimulation are nonlinear under some conditions, and many neuronal
      components demonstrate strong nonlinear behavior. In spite of this, temporal and
      frequency dynamics of neural populations to sensory stimulation have been usually
      analyzed with linear approaches. NEW METHOD: In this paper, we propose the use of
      Noise-Assisted Multivariate Empirical Mode Decomposition (NA-MEMD), a data-driven
      template-free algorithm, plus the Hilbert transform as a suitable tool for
      analyzing population oscillatory dynamics in a multi-dimensional space with
      instantaneous frequency (IF) resolution. RESULTS: The proposed approach was able
      to extract oscillatory information of neurophysiological data of deep vibrissal
      nerve and visual cortex multiunit recordings that were not evidenced using linear
      approaches with fixed bases such as the Fourier analysis. COMPARISON WITH
      EXISTING METHODS: Texture discrimination analysis performance was increased when
      Noise-Assisted Multivariate Empirical Mode plus Hilbert transform was
      implemented, compared to linear techniques. Cortical oscillatory population
      activity was analyzed with precise time-frequency resolution. Similarly, NA-MEMD
      provided increased time-frequency resolution of cortical oscillatory population
      activity. CONCLUSIONS: Noise-Assisted Multivariate Empirical Mode Decomposition
      plus Hilbert transform is an improved method to analyze neuronal population
      oscillatory dynamics overcoming linear and stationary assumptions of classical
      methods.

PMID- 27044802
TI  - Animal models of post-traumatic epilepsy.
AB  - Post-traumatic epilepsy (PTE) is defined as the development of unprovoked
      seizures in a delayed fashion after traumatic brain injury (TBI). PTE lies at the
      intersection of two distinct fields of study, epilepsy and neurotrauma. TBI is
      associated with a myriad of both focal and diffuse anatomic injuries, and an
      ideal animal model of epilepsy after TBI must mimic the characteristics of human
      PTE. The three most commonly used models of TBI are lateral fluid percussion,
      controlled cortical injury, and weight drop. Much of what is known about PTE has
      resulted from use of these models. In this review, we describe the most commonly
      used animal models of TBI with special attention to their advantages and
      disadvantages with respect to their use as a model of PTE.

PMID- 27044803
TI  - The face-responsive M170 is modulated by sensor selection: An example of
      circularity in the analysis of MEG-data.
AB  - BACKGROUND: Magnetoencephalography (MEG) experiments create large data sets
      obtained from many sensors at different locations. Therefore, a process of sensor
      selection prior to hypothesis-driven data analysis is common, e.g., when studying
      the face-selective M170 component occurring at temporal sites around 170ms post
      stimulus. However, the strategies to identify sensors of interest vary across
      investigations, and frequently the contrast used for sensor-selection is not
      independent from the contrast between experimental conditions. NEW METHOD: We re
      analyzed data from a previously published MEG-experiment where participants
      viewed faces of either a loved person or two friends. We included different
      strategies for identifying face-responsive sensors based on all or each one of
      the face-categories before comparing M170 amplitudes across conditions. RESULTS:
      When sensor-selection was based on signal strength elicited by one experimental
      condition alone, a comparison across face-categories revealed significantly
      increased M170 amplitudes for the respective face category. Conducting the same
      analysis following sensor-selection based on averaged activity across all face
      categories did not yield different M170 amplitudes. COMPARISON WITH EXISTING
      METHOD: Whereas this pitfall of selective analysis has been studied and discussed
      in detail for fMRI methods there is no comparable re-analysis of real EEG/MEG
      data. CONCLUSIONS: Our results demonstrate that selection-bias is as relevant for
      EEG/MEG analysis as for fMRI methods. Sensor-selection must be independent from
      the contrast analyzed with statistical comparisons, because otherwise a distorted
      or 'circular' analysis might result.

PMID- 27044804
TI  - Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation,
      Protects Pancreatic beta-Cells from Apoptosis, and Prevents Type 2 Diabetes
      Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet.
AB  - Intraperitoneal injection of arglabin (2.5 ng/g of body weight, twice daily, 13
      weeks) into female human apolipoprotein E2 gene knock-in (ApoE2Ki) mice fed a
      high-fat Western-type diet (HFD) reduced plasma levels of glucose and insulin by
      ~20.0% +/- 3.5% and by 50.0% +/- 2.0%, respectively, in comparison with vehicle
      treated mice. Immunohistochemical analysis revealed the absence of active caspase
      3 in islet sections from ApoE2Ki mice fed a HFD and treated with arglabin. In
      addition, arglabin reduced interleukin-1beta (IL-1beta) production in a
      concentration-dependent manner in Langerhans islets isolated from ApoE2Ki mice
      treated with lipopolysaccharide (LPS) and with cholesterol crystals. This
      inhibitory effect is specific for the inflammasome NOD-like receptor family,
      pyrin domain-containing 3 (NLRP3) because IL-1beta production was abolished in
      Langerhans islets isolated from Nlrp3(-/-) mice. In the insulin-secreting INS-1
      cells, arglabin inhibited, in a concentration-dependent manner, the maturation of
      pro-IL-1beta into biologically active IL-1beta probably through the inhibition of
      the maturation of procaspase-1 into active capsase-1. Moreover, arglabin reduced
      the susceptibility of INS-1 cells to apoptosis by increasing Bcl-2 levels.
      Similarly, autophagy activation by rapamycin decreased apoptosis susceptibility
      while autophagy inhibition by 3-methyladenin treatment promoted apoptosis.
      Arglabin further increased the expression of the autophagic markers Bcl2
      interacting protein (Beclin-1) and microtubule-associated protein 1 light chain 3
      II (LC3-II) in a concentration-dependent manner. Thus, arglabin reduces NLRP3
      dependent inflammation as well as apoptosis in pancreatic beta-cells in vivo and
      in the INS-1 cell line in vitro, whereas it increases autophagy in cultured INS-1
      cells, indicating survival-promoting properties of the compound in these cells.
      Hence, arglabin may represent a new promising compound to treat inflammation and
      type 2 diabetes mellitus development.

PMID- 27044805
TI  - SATB1 promotes prostate cancer metastasis by the regulation of epithelial
      mesenchymal transition.
AB  - Special AT-rich sequence binding protein 1 (SATB1) plays important role in the
      regulation of chromatin structure and gene expression. Recent studies have
      indicated oncogenic role of SATB1. However, the function of SATB1 in prostate
      cancer progression and metastasis remains unclear. In this study SATB1 expression
      vector or siRNA was employed to modulate the expression level of SATB1 in
      prostate cancer cells and xenograft tumor in nude mouse model.
      Immunohistochemical analysis was performed on clinical prostate cancer samples.
      Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude
      mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous
      tumor in nude mice. Immunohistochemical and Western blot analysis of the
      xenografts showed that silencing SATB1 led to decreased expression of vimentin
      and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led
      to increased expression of vimentin and MMP2 and decreased expression of E
      cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased
      significantly while E-cadherin expression was reduced significantly in clinical
      samples of prostate carcinoma with metastasis compared to prostate carcinoma
      without metastasis and benign prostate hyperplasia. Taken together, these
      findings suggest that the modulation of epithelial-mesenchymal transition by
      SATB1 may contribute to prostate cancer metastasis. 

PMID- 27044806
TI  - Fish oil augments celecoxib mediated alteration in apoptotic pathway in the
      initiation phase of 7,12-dimethylbenz(alpha)anthracene-induced mammary
      carcinogenesis.
AB  - BACKGROUND: Resistance in apoptosis by disruption in signaling pathways is a
      common trait in malignancy. Celecoxib, a specific COX-2 inhibitor, has been
      reported to exert chemopreventive effect by inducing apoptosis. However, high
      doses or chronic usage of celecoxib for longer periods have various side effects.
      n-3 PUFA rich fish oil also abrogates COX-2 expression in tumors and thereby, has
      chemopreventive action. Combinatorial strategy using these two has been reported
      to be beneficial in mammary carcinoma. The present study was designed to
      understand the role of intrinsic and extrinsic apoptotic pathways in
      chemopreventive effect of celecoxib and fish oil in the initial phases of mammary
      carcinogenesis. METHODS: Female Wistar rats were distributed into control and
      DMBA treated groups and further subdivided based on pretreatment with celecoxib
      and/or fish oil. The animals were subsequently maintained for 90 days and then
      sacrificed. The proteins involved in intrinsic and extrinsic pathways were
      assessed in isolated mammary epithelial cells using flowcytometry. RESULTS: An
      increase in Bax, Bcl-2, Fas, FasL and caspase 8 levels was observed in DMBA
      treated animals. Celecoxib and/or fish oil further upregulate Bax, Fas, Fas L and
      caspase-8 while Bcl-2 levels were decreased. However maximal effect was observed
      with combinatorial dose of celecoxib and fish oil regimen. CONCLUSION:
      Administration of a combinatorial therapy of fish oil and celecoxib in mammary
      carcinoma exert better chemopreventive effect by modulation of both intrinsic and
      extrinsic apoptotic pathways.

PMID- 27044807
TI  - Y-box-binding protein 1 promotes tumor progression and inhibits cisplatin
      chemosensitivity in esophageal squamous cell carcinoma.
AB  - Y-box-binding protein 1 (YB-1) has been identified as a pleotropic oncoprotein in
      multiple human malignancies and is involved in the regulation of various DNA/RNA
      dependent events, including transcription and translation. However, little is
      known about expression pattern and underlying functions of YB-1 in esophageal
      squamous cell carcinoma (ESCC). In this study, we report that up-regulated YB-1
      is closely correlated with TNM stage and tumor size in ESCC specimens and
      predicts a poor prognosis in ESCC patients. Genetic silencing of YB-1 inhibits
      cell proliferation and invasive potential by regulating its targeted genes
      associated with tumor growth and metastasis. In particular, we also show that
      silencing of YB-1 enhances chemotherapy-induced cytotoxicity in EC109 and TE-1
      cells by targeting multidrug resistance 1 (MDR1). Our findings demonstrate the
      oncogenic roles of YB-1 in ESCC and support it as a target for ESCC therapy. 

PMID- 27044808
TI  - The expression of TSSC3 and its prognostic value in patients with osteosarcoma.
AB  - Osteosarcoma is one of the most common primary bone tumors in children and
      adolescents, typically presenting with poor prognosis. Recent studies have found
      that TSSC3 had a potential capability in suppressing the tumor development in
      osteosarcoma. Our purpose was to explore the role of TSSC3 in the clinical
      outcome of osteosarcoma patients. Firstly, we detected the expression of TSSC3 at
      mRNA level by quantitative real-time polymerase chain reaction (qRT-PCR). The
      result demonstrated that TSSC3 expression was lower in osteosarcoma patients than
      in healthy controls (P<0.05). Then, the relationship between TSSC3 and
      clinicopathological characteristics was analyzed by chi-square test which
      manifested that WHO grade, metastasis, and recurrence were vital influential
      factors on the expression of TSSC3 (P<0.05). We also estimated the association
      between TSSC3 and overall survival of osteosarcoma patients by Kaplan-Meier
      analysis as well as assessed the prognostic value of TSSC3 and
      clinicopathological characteristics through cox regression analysis. Patients
      with high TSSC3 expression were proved to live longer than those with low TSSC3
      expression (log rank test, P<0.05). TSSC3 expression (P=0.032, HR=0.405,
      95%CI=0.177-0.926) and metastasis (P=0.010, HR=2.849, 95%CI=1.291-6.287) were
      considered to be independent prognostic factors in osteosarcoma. Taken together,
      our findings provided preliminary evidence that the TSSC3 was a prognostic marker
      in osteosarcoma and this might be useful for the therapy of osteosarcoma. 

PMID- 27044809
TI  - Synergistic and attenuated effect of HSS in combination treatment with docetaxel
      plus cisplatin in human non-small-cell lung SPC-A-1 tumor xenograft.
AB  - Platinum based combination regimens are first-line treatment option in treatment
      of non-small cell lung cancer (NSCLC) but the clinical utility has been limited
      because of their toxicities. Many reports indicated that patients with tumors can
      benefit from adjuvant chemotherapy drugs. The aim of this study was to confirm
      adjuvant chemotherapy of HSS with docetaxel plus cisplatin (DP) against NSCLC by
      evaluating antitumor activity and attenuated effect. In vivo SPC-A-1 xenograft
      model was established to evaluate antitumor activity and toxicity of HSS along or
      combination with DP. Evaluation indexes include the relative tumor proliferation
      rate, tumor growth inhibition rate, body weight, food consumption, hematological
      and biochemical analysis. HSS treatment showed inhibited tumor growth and
      increased tumor inhibition of DP treatment at doses of 250 mg/kg and 500 mg/kg.
      No significant toxicity was found in HSS-treated mice, but significant toxicity
      was found in DP-treated mice. HSS combination with DP could reduce toxicity of DP
      treatment by improving body weight and food consumption, and increasing the
      number of WBC and PLT, decreasing the level of ALT, AST and BUN. HSS combined
      with DP treatment has additive effect which contributes to enhance tumor growth
      inhibition of DP treatment and attenuated effect which contributes to reduce
      toxicity of DP treatment. These findings indicate potential benefit for use of
      HSS adjuvant chemotherapy for NSCLC treatment.

PMID- 27044810
TI  - Diallyl trisulfide attenuates ethanol-induced hepatic steatosis by inhibiting
      oxidative stress and apoptosis.
AB  - Inhibiting the major characteristics of alcoholic fatty liver (AFL) such as lipid
      accumulation, oxidative stress and apoptosis is a promising strategy of treating
      AFL. Diallyl trisulfide (DATS) is the major constituent isolated from garlic,
      which shows promise in the treatment of chronic liver disease. However, the
      effects of DATS on ethanol-induced liver injury and the related mechanisms remain
      unclear. The aim of this study was to evaluate the potential protective effects
      of DATS on AFL and the potential mechanisms. A single intragastric dose of
      ethanol was given to rats in vivo, while ethanol-stimulated LO2 cells were used
      as an in vitro model. Our results demonstrated that DATS prevented ethanol
      induced injury, as indicated by the reduced activities of aspartate transaminase
      (AST) and alanine aminotransferase (ALT) in the serum and culture medium, and
      inhibition of cell apoptosis. Furthermore, DATS reduced hepatic steatosis by up
      regulating the expression of peroxisome proliferator-activated receptor-alpha
      (PPAR-alpha) and down-regulating the expression of sterolregulatory element
      binding protein 1c(SREBP-1c). In addition, DATS alleviated ethanol-induced
      oxidative stress by enhancing non-enzymatic antioxidant and enzymatic
      antioxidants contents and by reducing the levels of reactive oxygen species (ROS)
      and malondialdehyde (MDA). These data collectively revealed that DATS protected
      ethanol-induced liver injury by inhibiting lipid accumulation and oxidative
      stress. 

PMID- 27044811
TI  - Protective effects of propolis on methotrexate-induced testis injury in rat.
AB  - Propolis is an adhesive substance which is collected and used by honeybees.
      Propolis is a potent antioxidant and a free radical scavenger. This study was
      designed to determine whether propolis could protect against dysfunction and
      oxidative stress induced by methotrexate-induced injury in rat testis. A total of
      40 male Wistar albino rats were divided into four groups: group 1 was the
      untreated control. On the eighth day of the experiment, groups 2 and 3 received
      single intraperitoneal injections of methotrexate (MTX) at 20mg/kg. Groups 3 and
      4 received 100mg/kg/day propolis (by oral gavage) for 15 days by the first day of
      the experimental protocol. Then the rats were decapitated under anesthesia, and
      their testes were removed. The histopathological and biochemical analysis along
      with apoptosis assessment of testis tissues were compared. Immunohistochemical
      analysis of Heat shock protein-70 (HSP-70) and Proliferating Cell Nuclear Antigen
      (PCNA) were performed. The phenolic characterization of propolis was performed by
      Liquid chromatography-mass spectrometry (LC-MS/MS). Methotrexate caused tended to
      increase in malondialdehyde level and in the number of apoptotic cells; it also
      caused a decrease in MSTD and JTBS, PCNA and HSP-70 expression and xanthine
      oxidase levels in group 2. Propolis prevented the rise in malondialdehyde,
      xanthine oxidase levels and HSP-70 expression and improved testicular morphology
      and JTBS. It was found that, methorexate gives rise to serious damage in the
      testes and propolis is a potent antioxidant agent in preventing testicular
      injury. 

PMID- 27044812
TI  - Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid
      arthritis.
AB  - This review is intended to provide a summary of the pathogenesis, diagnosis and
      therapies for rheumatoid arthritis. Rheumatoid arthritis (RA) is a common form of
      inflammatory autoimmune disease with unknown aetiology. Bone degradation,
      cartilage and synovial destruction are three major pathways of RA pathology.
      Sentinel cells includes dendritic cells, macrophages and mast cells bound with
      the auto antigens and initiate the inflammation of the joints. Those cells
      further activates the immune cells on synovial membrane by releasing inflammatory
      cytokines Interleukin 1, 6, 17, etc., Diagnosis of this disease is a
      combinational approach comprises radiological imaging, blood and serology markers
      assessment. The treatment of RA still remain inadequate due to the lack of
      knowledge in disease development. Non-steroidal anti-inflammatory drugs, disease
      modifying anti rheumatic drugs and corticosteroid are the commercial drugs to
      reduce pain, swelling and suppressing several disease factors. Arthroscopy will
      be an useful method while severe degradation of joint tissues. Gene therapy is a
      major advancement in RA. Suppressor gene locus of inflammatory mediators and
      matrix degrading enzymes were inserted into the affected area to reduce the
      disease progression. To overcome the issues aroused from those therapies like
      side effects and expenses, phytocompounds have been investigated and certain
      compounds are proved for their anti-arthritic potential. Furthermore certain
      complementary alternative therapies like yoga, acupuncture, massage therapy and
      tai chi have also been proved for their capability in RA treatment. 

PMID- 27044813
TI  - Histone modifications patterns in tissues and tumours from acute promyelocytic
      leukemia xenograft model in response to combined epigenetic therapy.
AB  - Xenograft models are suitable for in vivo study of leukemia's pathogenesis and
      the preclinical development of anti-leukemia agents but understanding of
      epigenetic regulatory mechanisms linking to adult cell functions in pathological
      conditions during different in vivo treatments is yet unknown. In this study, for
      the first time epigenetic chromatin modifications were characterized in tissues
      and tumours from murine xenograft model generated using the human acute
      promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice.
      Xenografts were subjected to combined epigenetic treatment by histone deacetylase
      inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and
      all-trans-retinoic acid based on in vitro model, where such combination inhibited
      NB4 cell growth and enhanced retinoic acid-induced differentiation to
      granulocytes. Xenotransplantation was assessed by peripheral blood cells counts,
      the analysis of cell surface markers (CD15, CD33, CD45) and the expression of
      certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment
      prolonged APL xenograft mice survival and prevented tumour formation. The
      analysis of the expression of histone marks such as acetylation of H4,
      trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues
      demonstrated tissue-specific changes in the level of histone modifications and
      the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic
      agents used in this study were positive for leukemia prevention and linked to a
      modulation of the chromatin epigenetic environment in adult tissues of malignant
      organism. 

PMID- 27044814
TI  - Tryptanthrin reduces mast cell proliferation promoted by TSLP through modulation
      of MDM2 and p53.
AB  - BACKGROUND: Atopic dermatitis (AD) results from complex interactions between mast
      cells and inflammatory mediators. An inflammatory mediator, thymic stromal
      lymphopoietin (TSLP) is known to promote mast cell proliferation through up
      regulation of mouse double minute 2 (MDM2, a negative regulator of p53) and
      aggravate AD. In this study, we investigated whether tryptanthrin (TR, an anti
      inflammatory agent) would regulate TSLP-induced mast cell proliferation and TSLP
      induced a pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha production
      from mast cells. METHODS: Human mast cell line (HMC-1) cells were treated with TR
      and stimulated with TSLP. Proliferation was measured with a bromodeoxyuridine
      incorporation assay. And pro- and anti-apoptotic factors were analyzed with
      quantitative real-time PCR, Western blot analysis, and ELISA. The mRNA expression
      and production of TNF-alpha were analyzed with quantitative real-time PCR and
      ELISA. RESULTS: TR significantly inhibited the proliferation of HMC-1 cells
      promoted by TSLP. TR inhibited MDM2 expression, whereas TR increased the
      expression of p53, poly ADP-ribose polymerase, and caspase-3 in the TSLP
      stimulated HMC-1 cells. TR significantly inhibited Ki67 mRNA expression as well
      as mRNA expression and production of interleukin (IL)-13 in the TSLP-stimulated
      HMC-1 cells. Moreover, TR significantly suppressed mRNA expression and production
      of TNF-alpha in the TSLP-stimulated HMC-1 cells. Finally, the mRNA expression of
      IL-7 receptor alpha chain and TSLP receptor was inhibited by TR in the TSLP
      stimulated HMC-1 cells. CONCLUSION: Our results suggest that TR determined with
      new concept has intensive potential for the treatment of mast cell-mediated
      allergic diseases, such as AD.

PMID- 27044815
TI  - BSA-binding properties and anti-proliferative effects of amino acids
      functionalized polyoxomolybdates.
AB  - Glycine decorated heteropolymolybdates, K2Na[AsMo6O21(O2CCH2NH3)3].6H2O 1 and
      K2Na2[gamma-Mo8O26(O2CCH2NH3)2].6H2O 2, have been synthesized and evaluated for
      in vitro anti-proliferative effects. The identity and high purity of compounds 1
      and 2 were confirmed by elemental analysis, FT-IR spectrum, UV-vis spectrum, and
      X-ray diffraction. Crystal data for 2: triclinic, P-1, a=9.792(2)A, b=10.077(2)A,
      c=10.351(2)A, alpha=83.865(4) degrees , beta=71.110(4) degrees , gamma=62.284(3)
      degrees , V=854.3(3)A(3), Z=1, R(final)=0.0486. The inhibitory effects of 1 and 2
      on human non-small cell lung cancer cell line A549 were investigated by MTT
      assay, nuclear staining, and the flow cytometry. It indicated that compound 1
      inhibited the proliferation of A549 cells in a dose-dependent and time-dependent
      manner, which is more effective than the positive control, 5-fluorouracil (5-FU)
      (P<0.05). The staining and flow cytometry results showed that compound 1 induced
      the apoptosis and necrosis of A549 cells and inhibit cell proliferation, which is
      associated with S-phase arrest. Compound 2 showed a modest activity in a dose
      dependent manner. In addition, the interaction between compound 1 and bovine
      serum albumin (BSA) was evaluated by spectroscopic methods. The results showed
      that the compound 1 effectively quenched the intrinsic fluorescence of BSA via
      static quenching and changed the conformation of BSA. 

PMID- 27044816
TI  - APOBEC3B expression in drug resistant MCF-7 breast cancer cell lines.
AB  - APOBEC3B belongs to a protein family of cytidine deaminases that can insert
      mutations in DNA and RNA as a result of their ability to deaminate cytidine to
      uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic
      source of DNA damage in breast cancers. We investigated APOBEC3B expression in
      four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel
      and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization
      technology (RNAscope) and compared expression levels with drug sensitive MCF-7
      cell line. After RNAscope staining, slides were scanned and saved as digital
      images using Aperio scanner and software. Quantitative scoring utilizing the
      number of punctate dots present within each cell boundary was performed for the
      parameters including positive cell percentage and signal intensity per positive
      cell. In Doxorubicin and Etoposide resistant MCF-7 cell lines, APOBEC3B
      expression was approximately five-fold increased (23% and 24% respectively) with
      higher signal intensity (1.92 and 1.44 signal/cell, respectively) compared to
      drug sensitive MCF-7 cell line (5%, 1.00 signal/cell) with statistical
      significance. The increase of APOBEC3B expression in Docataxel resitant and
      Paclitaxel resistant MCF-7 cell lines was not very high. In conclusion, APOBEC3B
      expression was increased in some population of tumor cells of drug resistant cell
      lines. At least for some drugs, APOBEC3B expression may be related to drug
      resistance, subjecting to some tumor cells to frequent mutation. 

PMID- 27044817
TI  - miR-221/222 enhance the tumorigenicity of human breast cancer stem cells via
      modulation of PTEN/Akt pathway.
AB  - BACKGROUND: The miR-221/222 cluster has been discovered to function as oncogene
      in human malignancies including breast cancer. However, the role of miR-221/222
      in the self-renewal of breast cancer stem cells (BCSCs) is not fully understood.
      In this study, we examined the impact and mechanism of miR-221/222 on the breast
      cancer cell viability, migration and invasion, and propagation of BCSCs. METHODS:
      Human breast cancer cell line MCF-7 was transfected with miR-221/222 mimics or
      inhibitors to overexpress or knock down miR-221/222 respectively using
      Lipofactamine 2000. The biological effects of miR-221 and miR-222 were then
      assessed by cell proliferation assay, colony formation assay and transwell
      chamber assays. CD44/CD24 staining and mammosphere formation assay were performed
      to evaluate the ability of BCSCs self-renewal. Potential target gene phosphatase
      and tensin homolog (PTEN) and its downstream effector, phosphorylated Akt (p-Akt)
      were identified by Western blot and qRT-PCR methods. RESULTS: PTEN, a tumor
      suppressor gene, was confirmed as a target of miR-221/222 in breast cancer cell
      line MCF-7. Downregulation of PTEN by miR-221/222 increased the phosphorylation
      of Akt. Enforced expression of miR-221/222 promoted breast cancer cell
      proliferation, migration and invasion via targeting PTEN/Akt pathway.
      Importantly, ectopic expression of miR-221/222 enriched the proportion of
      CD44(+)/CD24(-) BCSCs and improved the mammosphere formation capacity through
      targeting PTEN/Akt pathway. Blocking the endogenous miR-221/222 restored PTEN
      expression and subsequently decreased Akt phosphorylation, and thereby reversed
      this phenotype. CONCLUSIONS: Our results suggested that miR-221/222 enhance
      breast cancer growth, migration and invasion, meanwhile propagate the self
      renewal of BCSCs. This is achieved possibly through targeting PTEN/Akt pathway.
      miR-221/222 might be a novel therapeutic candidate for human breast cancer.

PMID- 27044818
TI  - Endostatin gene therapy inhibits intratumoral macrophage M2 polarization.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a highly vascularized cancer resistant
      to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune
      cells, with macrophages being the most abundant cell type. Alternatively
      activated M2 macrophages are known to contribute to tumor progression. Endostatin
      (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In
      this study, we investigated the impact of ES gene therapy on the polarization of
      tumor-associated macrophages (TAMs) in lung metastases from tumor-bearing mice.
      METHODS: BALB/c mice divided into three groups: Normal, Control and ES-treated.
      Tumor-bearing mice were treated with ES-transduced cells or control cells over
      ten days. At the end of the study, plasma was collected, and pulmonary
      macrophages were isolated and used for FACS or RT-PCR. ELISA tests were used to
      analyze plasma and cell culture supernatant cytokines. RESULTS: ES treatment
      significantly reduced the levels of anti-inflammatory and pro-angiogenic
      cytokines, including IL4, IL-10, IL-13 and VEGF. Gene expression of M2 markers,
      such as IL-10, Arg-1, VEGF and YM-1, declined significantly. Flow cytometry
      showed a reduction in the number of M2 F4/80+CD36+CD206+CD209+ macrophages and in
      IL-10 secretion by these cells. Reduced levels of IL-10 were also found in the
      culture supernatants of the ES-treated group. CONCLUSIONS: Our research
      corroborates previous observations that ES has an important anti-tumoral role.
      However, aside from promoting interferon-? secretion and an effective T cell
      response, we show here that this switch is extended to TAMs, complicating the
      maintenance of pro-tumorigenic M2 macrophages and thus favoring tumor
      elimination.

PMID- 27044819
TI  - Pristimerin inhibits proliferation, migration and invasion, and induces apoptosis
      in HCT-116 colorectal cancer cells.
AB  - Colorectal cancer (CRC) is one of the world's most common cancers with a high
      mortality rate mainly due to metastasis. Our previous study showed that
      pristimerin had potent antitumor activities against human CRC cells. In the
      present study, we further evaluated pristimerin anti-tumor and anti-metastatic
      properties. MTT assay, Hoechst staining, Annexin V/PI double staining, reactive
      oxygen species (ROS) measurements were used to assess pristimerin cytotoxicity
      and apoptotic-inducing effects on HCT-116 cells. Wound healing assay and
      Transwell assay were used to estimate pristimerin anti-migration and anti
      invasion activities on CRC cells. Meanwhile, HCT-116 xenograft model applied for
      investigating in vivo antitumor activities. Our results showed that pristimerin
      mediated in vitro HCT-116 cell death, through generation of intracellular ROS and
      apoptosis induction. Tumor volumes and weights measurements, pathological
      analysis and Tunnel assay proved that pristimerin inhibited in vivo HCT-116
      xenografts growth. Pristimerin was also able to limit CRC invasion and
      metastasis. It caused downregulation of PI3K/AKT/mTOR pathway and its subsequent
      downstream p70S6K and E4-BP1 proteins. Collectively, pristimerin exerted both in
      vitro and in vivo cytotoxic and anti-metastatic effects on HCT-116 cells,
      suggesting that pristimerin has potential as a new anticancer drug for treatment
      of colon cancer. 

PMID- 27044820
TI  - Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a
      model of osteoarthritis induced by anterior cruciate ligament transection in
      ovariectomised rats.
AB  - CONTEXT: The efficacy of the combination chondroitin sulfate-glucosamine (CS
      GlcN) in the treatment of knee osteoarthritis (OA) has been suggested in recent
      clinical studies. In vitro reports have also suggested anti-inflammatory and anti
      resorptive effects of this combination. OBJECTIVE: The aim of this study was to
      characterize the effects of CS-GlcN on joint degradation in vivo including the
      assessment of inflammation and bone metabolism in a model of OA. MATERIALS AND
      METHODS: We have used the OA model induced by anterior cruciate ligament
      transection (ACLT) in ovariectomised rats. CS-GlcN was administered daily (oral
      gavage) from week 0 until week 12 after ovariectomy at the dose of 140 (CS)+175
      (GlcN)(HCl) mg/kg. Histochemical analyses were performed, the levels of
      biomarkers and inflammatory mediators were measured by luminex or ELISA and bone
      microstructure was determined by MUCT. RESULTS: CS-GlcN protected against
      cartilage degradation and reduced the levels of inflammatory mediators such as
      interleukin-1beta and tumor necrosis factor-alpha in the affected knee. In
      addition, serum biomarkers of inflammation and cartilage and bone degradation
      including matrix metalloproteinase-3, C-telopeptide of type II collagen and the
      ratio receptor activator of nuclear factor kappaB ligand/osteoprotegerin were
      significantly decreased by CS-GlcN. This treatment also tended to improve some
      bone microstructural parameters without reaching statistical significance.
      DISCUSSION AND CONCLUSIONS: These results demonstrate the chondroprotective
      effects of CS-GlcN in vivo, in the experimental model of ACLT in ovariectomised
      rats, and suggest that this combination may be useful to control the joint
      catabolic effects of inflammatory stress. These findings could have clinical
      relevance related to the prevention of joint degradation by CS-GlcN and support
      the potential development of OA treatments based on this combination.

PMID- 27044821
TI  - Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive
      activity in peripheral blood mononuclear cells from patients with HTLV1
      associated myelopathy.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) induces a strong activation of the
      immune system, especially in individuals with HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). Physalin F is a secosteroid
      with potent anti-inflammatory and immunomodulatory activities. The present study
      aimed to investigate the effects of physalin F on peripheral blood mononuclear
      cells (PBMC) of HAM/TSP subjects. A concentration-dependent inhibition of
      spontaneous proliferation of PBMC from HAM/TSP subjects was observed in the
      presence of physalin F, as evaluated by (3)H-thymidine uptake. The IC50 for
      physalin F was 0.97 +/- 0.11 MUM. Flow cytometry analysis using Cytometric Bead
      Array (CBA) showed that physalin F (10 MUM) significantly reduced the levels of
      IL-2, IL-6, IL-10, TNF-alpha and IFN-gamma, but not IL-17A, in supernatants of
      PBMC cultures. Next, apoptosis induction was addressed by using flow cytometry to
      evaluate annexin V expression. Treatment with physalin F (10 MUM) increased the
      apoptotic population of PBMC in HAM/TSP subjects. Transmission electron
      microscopy analysis of PBMC showed that physalin F induced ultrastructural
      changes, such as pyknotic nuclei, damaged mitochondria, enhanced autophagic
      vacuole formation, and the presence of myelin-like figures. In conclusion,
      physalin F induces apoptosis of PBMC, decreasing the spontaneous proliferation
      and cytokine production caused by HTLV-1 infection.

PMID- 27044822
TI  - Procyanidins from Nelumbo nucifera Gaertn. Seedpod induce autophagy mediated by
      reactive oxygen species generation in human hepatoma G2 cells.
AB  - In this study, autophagic effect of procyanidins from lotus (Nelumbo nucifera
      Gaertn.) seedpod (LSPCs) on human hepatoma G2 (HepG2) cells, and the inherent
      correlation between autophagic levels and reactive oxygen species (ROS)
      generation were investigated. The results showed that LSPCs increased
      monodansylcadaverine (MDC) fluorescence intensity and LC3-I/LC3-II conversion in
      HepG2 cells. In addition, the typically autophagic characteristics
      (autophagosomes and autolysosomes) were observed in LSPCs-treated cells, but not
      found in the cells treated with autophagy inhibitor 3-methyladenine (3-MA).
      Furthermore, the elevated ROS level was in line with the increasing of autophagy
      activation caused by LSPCs, however, both 3-MA and the ROS scavenger N
      acetylcyteine (NAC) inhibitors effectively suppressed the autophagy and ROS
      generation triggered by LSPCs. As a result, these results indicated that LSPCs
      induced HepG2 cell autophagy in a time- and dose-dependent manner, and promoted
      reactive oxygen species (ROS) generation on HepG2 cells. Moreover, we found that
      LSPCs caused DNA damage, S phase arrest and the decrement of mitochondria
      membrane potential (MMP) which were associated with ROS generation. In summary,
      our findings demonstrated that the LSPCs-induced autophagy and autophagic cell
      death were triggered by the ROS generation in HepG2 cells, which might be
      associated with ROS generation through the mitochondria-dependent signaling way. 

PMID- 27044823
TI  - miR-935 promotes gastric cancer cell proliferation by targeting SOX7.
AB  - Gastric cancer is the most common cancer in the world, miRNAs have been
      demonstrated to play critical role in the development and progression of gastric
      cancer, such as miR-7, miR-217 and miR-335. Here, we found miR-935 was
      upregulated in gastric cancer tissues and cells. Overexpression of miR-935
      promoted cell proliferation and tumorigenesis in vitro determined by MTT
      analysis, colony formation analysis, BrdU cell proliferation analysis and soft
      agar growth analysis, knockdown of miR-935 reduced these effects. Tumor
      suppressor sex-determining region Y-box 7 (SOX7) was the direct target of miR
      935, overexpression of miR-935 inhibited SOX7 expression, but promoted the levels
      CCND1 and C-MYC which promotes cell proliferation and tumorigenesis, knockdown of
      miR-935 increased SOX7 level, and inhibited CCND1 and C-MYC expression.
      Synchronous knockdown of miR-935 and SOX7 promoted cell proliferation and
      tumorigenesis in vitro, confirming miR-935 regulated gastric cancer cell
      proliferation by inhibiting SOX7. In summary, we found miR-935 contributed to
      cell proliferation of gastric cancer through targeting SOX7. 

PMID- 27044824
TI  - Downregulation of IL-10 secretion by Treg cells in osteoarthritis is associated
      with a reduction in Tim-3 expression.
AB  - Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and
      disability in the knee. Though traditionally thought a mechanical wear-and-tear
      disease, in recent years, knee OA as a low-grade, chronic inflammatory disease
      has been increasingly recognized. In this study, we examined the Treg responses
      in non-obese knee OA patients at different stages. Significantly elevated
      frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on
      the other hand, lower IL-10 secretion from Tregs in OA patients was observed.
      Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression
      on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the
      majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in
      OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA
      patients in more advanced stages showed further reductions in IL-10 and Tim-3
      expression. In conclusion, our results revealed an immunoregulatory disorder in
      OA independent of obesity, and demonstrated a potential mechanism in establishing
      the proinflammatory status of OA patients. 

PMID- 27044825
TI  - Soluble CD40 ligands sensitize the epithelial ovarian cancer cells to cisplatin
      treatment.
AB  - OBJECTIVE: CD154 (CD40L) is a protein that is primarily expressed on activated T
      cells and is a member of the TNF superfamily of molecules. It binds to CD40 on
      antigen-presenting cells (APC), which leads to many effects depending on the
      target cell type. Being an activator of immune cells, CD40L has also been shown
      to directly induce apoptosis in tumor cells by multiple mechanisms. To understand
      the role of sCD40L in regulating the proliferation of epithelial ovarian cancer
      cells treated or untreated with cisplatin. METHODS: Epithelial ovarian cancer
      cells: SKOV3 and its cisplatin-resistant strain SKOV3/DDP cells were used to test
      the effect of sCD40L and cisplatin. The proliferation of SKOV3 and SKOV3/DDP
      cells were measured by MTT. Cell cycle was assessed by flow cytometry. The mRNA
      expressions of targeted genes were detected by qRT-PCR. The protein expressions
      were detected by Western blotting. RESULTS: sCD40L showed a significant dose
      dependence inhibitory effect on the proliferation of ovarian cancer cell lines.
      sCD40L in combination with cisplatin could sensitized SKOV3/DDP cells to
      cisplatin treatment and reversed the drug resistance of SKOV3/DDP cells. The
      reversal ratios of 1 MUg/ml sCD40L combined with cisplatin in SKOV3 and SKOV3/DDP
      cells were 2.11, 2.71, while the reversal ratios of 2 MUg/ml sCD40L combined with
      cisplatin in SKOV3 and SKOV3/DDP cells were 3.78, 5.20, respectively. sCD40L or
      sCD40L combined cisplatin increased tumor cells in G0/G1 phase. sCD40L in
      combination with cisplatin decreased the expression levels of GST-pi, LRP,
      Survivin, p53 and Bcl-2 in both epithelial ovarian cancer cell lines. The protein
      expression level of GST-pi, LRP and P53 protein was also decreased upon sCD40L in
      combination with cisplatin although the expression level of Bcl-2 and survivin
      protein had no significant difference. CONCLUSION: sCD40L inhibits the
      proliferation of SKOV3 and SKOV3/DDP cells. The combined application of sCD40L
      and cisplatin can strength the inhibitory effect of cisplatin, and to a certain
      extent, reversing the resistance to cisplatin in SKOV3/DDP cells. sCD40L could
      lead a cell block in G0/G1 phase and make the cell growth restrained. sCD40L
      could induce SKOV3 and SKOV3/DDP cells apoptosis and reverse drug resistance
      through cutting GST-pi mRNA, LRP mRNA, survivin mRNA, p53 mRNA and Bcl-2 mRNA and
      decreasing the expression of GST-pi, LRP and P53 protein in SKOV3 and SKOV3/DDP
      cells, which provides in-vivo experiment basis to the application of sCD40L as a
      drug improving ovarian cancer cells sensitivity to cisplatin.

PMID- 27044826
TI  - The protective effects of bone marrow-derived mesenchymal stem cell (BMSC) on LPS
      induced acute lung injury via TLR3-mediated IFNs, MAPK and NF-kappaB signaling
      pathways.
AB  - The study attempted to clarify the protective role of bone marrow-derived
      mesenchymal stem cell (BMSC) transplantation on LPS-induced acute lung injury
      (ALI) of rats. BMSC were obtained from bone marrow of rat, cultured and
      proliferated in vitro. Rats of ALI were established through lipopolysaccharide
      (LPS) administration. Male rats were allocated to control group, ALI group and
      BMSC, transplantation group. Rats were sacrificed after BMSC injection after 12h,
      24h and 48h. Here we investigated the role of BMSC in LPS-induced alveolar
      macrophages to further demonstrate the mechanism of BMSC to lung injury. TLR3, a
      member of Toll-like receptor family, has been found in macrophages and the cell
      surface. In our study, first BMSC successfully reversed LPS-induced lung injury
      by hematoxylin-eosin (H&E) staining, ameliorated apoptosis via TUNEL and flow
      cytometer analysis, as well as improved cell structure. And then, western blot,
      quantitative real-time PCR, immunohistochemistry and immunofluorescence analysis
      were used to confirm that TLR3 was significantly down-regulated for BMSC
      treatment. Subsequently, TRIF and RIP1, down-streaming signals of TLR3, were
      inhibited greatly, leading to TRAF3, MAPK as well as NF-kappaB inactivity. Our
      results indicated that BMSC transplantation group displayed inhibitory effects on
      interferon (IFNs) levels via TLR3 in LPS-induced ALI and preventive effects on
      inflammation response via TLR3-regualted MAPK and NF-kappaB signaling pathway in
      LPS-induced lung injury. The present study indicated that BMSC could display
      protective effects on LPS-induced ALI and provide an experimental basis for
      clinical therapy. 

PMID- 27044827
TI  - Long noncoding RNA HULC predicts poor clinical outcome and represents pro
      oncogenic activity in diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer
      related mortality, and responds badly to existing treatment. Thus, it is of
      urgent need to identify novel prognostic markers and therapeutic targets of
      DLBCL. Emerging studies have implicated that long noncoding RNAs (lncRNAs) are
      differentially expressed in various tumors and play an important role in the
      development of cancer. Previously, our group has reported that the novel lncRNA
      HULC has important biological function and clinical potential in human pancreatic
      cancer. Here, we investigated the expression of HULC in a cohort of DLBCL to
      assess its expression pattern, clinical value and molecular mechanism. Firstly,
      we found that HULC was remarkably overexpressed in both DLBCL tissues and cell
      lines. Moreover, we illustrated that HULC was closely related to DLBCL
      characteristics, such as Ann Arbor stages, B symptoms, CHOP-like treatment,
      rituximab and IPI. Importantly, we verified that HULC was an key predictive
      factor for DLBCL diagnosis and prognosis from sizable samples through the long
      time follow-ups. Furthermore, we reveal that the HULC knockdown could
      significantly arrest cell proliferation and induce apoptosis by repressing cyclin
      D1 and Bcl-2 in DLBCL cells. Our results suggested that HULC could represent a
      novel indicator of poor prognosis and may be served as a potential target for the
      diagnosis and gene therapy of DLBCL. 

PMID- 27044828
TI  - Preparation and evaluation a new generation of low molecular weight heparin.
AB  - Enoxaparin is widely used in clinic, but it has some disadvantages. For example,
      its anticoagulant activity is weaker compared with heparin and it can not be
      effectively neutralizad by protamine sulfate (PS) in case of bleeding. Therefore,
      in this work, a new generation of low molecular weight heparin (NG-LMWH) was
      prepared.The NG-LMWH was prepared with the method of alkaline beta-elimination
      followed by gel chromatography. Estimating the molecular weight of the NG-LMWH by
      GPC-HPLC, it has a remarkably low polydispersity index and narrow molecular
      weight distribution. The polydispersity index of NG-LMWH was 1.052, which was
      lower than heparin (1.5) and enoxaparin (1.279). Anti-FXa and anti-FIIa potency
      of NG-LMWH was much higher than that of Enoxaparin, and close to that of heparin,
      which was determined by chromogenic substrate method. To test the degree of anti
      FXa or anti-FIIa potency neutralized by PS, equivalent anti-FXa or anti-FIIa
      activity doses of different anticoagulant in plasma were titrated with increasing
      amounts of PS in plasma. The results indicate that NG-LMWH was more efficiently
      neutralized by PS than enoxaparin.The efficacy of anti-thrombus of NG-LMWH was
      superior to enoxaparin and the effect was dose dependent, which was evaluated
      with rat carotid artery thrombosis and inferior vena cava thrombosis model. The
      results of pharmacokinetics in New Zealand rabbits showed that the
      pharmacokinetic characteristics of NG-LMWH were similar to enoxaparin. The NG
      LMWH prepared in this work has both advantages of heparin and enoxaparin with
      more effective and safer anticoagulation than enoxaparin. 

PMID- 27044829
TI  - The effect of aloe vera on ischemia--Reperfusion injury of sciatic nerve in rats.
AB  - PURPOSE: Aloe vera is compound which has strong antioxidant and anti-inflammatory
      effects. We investigated the neuroprotective role of aloe vera treatment in rats
      with experimental sciatic nerve ischemia/reperfusion injury. METHODS: Twenty
      eight male Wistar Albino rats were divided equally into 4 groups. Groups; Control
      group (no surgical procedure or medication), sciatic nerve ischemia/reperfusion
      group, sciatic nerve ischemia/reperfusion+aloe vera group and sciatic nerve
      ischemia/reperfusion+methylprednisolone group. Ischemia was performed by clamping
      the infrarenal abdominal aorta. 24 hours after ischemia, all animals were
      sacrificed. Sciatic nerve tissues were also examined histopathologically and
      biochemically. RESULTS: Ischemic fiber degeneration significantly decreased in
      the pre-treated with aloe vera and treated with methylprednisolone groups,
      especially in the pre-treated with aloe vera group, compared to the sciatic nerve
      ischemia/reperfusion group (p<0.05). A significant decrease in MDA, an increase
      in NRF1 level and SOD activity were observed in the groups which obtained from
      the AV and MP groups when compared to the sciatic nerve ischemia/reperfusion
      group. When all results were analysed it was seen that the aloe vera group was
      not statistically different compared to the MP group (p>0.05). CONCLUSIONS: Aloe
      vera is effective neuroprotective against sciatic nerve ischemia/reperfusion
      injury via antioxidant and anti-inflammatory properties. Also aloe vera was found
      to be as effective as MP.

PMID- 27044830
TI  - Long-circulating and liver-targeted nanoassemblies of cyclic phosphoryl N
      dodecanoyl gemcitabine for the treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a serious cancer with high mortality worldwide.
      Gemcitabine (GEM) is easily degraded in the circulation and has no tumor-targeted
      effect. In our previous research, an amphiphilic GEM derivative, cyclic
      phosphoryl N-dodecanoyl gemcitabine (CPDG) was prepared based on the techniques
      of HepDirect prodrug and self-assembled drug delivery systems (SADDS), which self
      assembled into the stable nanoassemblies in water. In this study, the long
      circulating nanoassemblies of CPDG/CHS-PEG1500 (9:1, mol/mol) were prepared for
      HCC treatment. In vitro and in vivo studies of the long-circulating CPDG
      nanoassemblies were explored. The degradation rates of CPDG depended on the
      media. CPDG showed much faster degradation in the acidic environment (pH 2.0)
      than the weak acidic and neutral media (pH 5.0, pH 7.4). However, the degradation
      half-life (t1/2) of CPDG was about 43h in the mouse plasma, longer than the t1/2
      at pH 2.0. Therefore, the long-circulating CPDG nanoassemblies could keep stable
      before reaching the targets in vivo. In the biodistribution study, the long
      circulating CPDG nanoassemblies were bolus intravenously (i.v.) injected into the
      hepatocellular tumor-bearing mice. The distribution of CPDG in the tumors was
      much higher than that in the blood, indicating the tumor targeting of the long
      circulating nanoassemblies. In the pharmacodynamic study, the long-circulating
      CPDG nanoassemblies were i.v. injected into the tumor-bearing mice with doses of
      (37.5, 75 MUmol/kg) compared with GEM (150 MUmol/kg). The mice were injected once
      every 3 days for totally 3 times. The long-circulating nanoassemblies nearly
      always showed the higher anti-cancer effects than GEM. The tumor inhibitory rates
      of GEM, the long circulating CPDG nanoassemblies (37.5, 75 MUmol/kg) were 49.54,
      42.97, 65.10%, respectively. Therefore, the long-circulating CPDG nanoassemblies
      had the much higher anti-cancer effect than GEM. The long-circulating CPDG
      nanoassemblies are promising nanomedicines to treat HCC. The combination design
      of tumor-targeted nanoassemblies based on HepDirect prodrug technique and SADDS
      theory is an effective method to modify the pharmacologically active nucleosides
      to treat some liver diseases.

PMID- 27044831
TI  - New pathways driving the experimental hepatoprotective action of tempol (4
      hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) against acute hepatotoxicity.
AB  - PURPOSE: In absence of liver protective drugs, a large number of hepatopathies
      may arise during drug administration. This study was executed to investigate the
      possible new pathways underlying the hepatoprotective effect of Tempol (4-hydroxy
      2,2,6,6- tetramethylpiperidine-1-oxyl), following oral administration of carbon
      tetrachloride in mice. METHODS AND RESULTS: Thirty albino mice were randomized
      into 3 equal groups. The duration of study was 28 days. The groups were
      classified as follows: Group I (healthy control): received saline, in the same
      volume of CCl4 dose, daily, orally, for 14 days, then sacrificed. Group II:
      received CCl4, as a single oral dose only, of 1 ml/kg body weight, dissolved in
      olive oil (1:1 v/v), the animals of this group were sacrificed 14 days after CCl4
      single dose intoxication. Group III (protective Tempol treated): received a
      single dose of Tempol, 20mg/kg, orally, daily for 14 days. Two hours after the
      last Tempol dose, animals of group III received a single oral dose of CCl4.
      Fourteen days later, animals were scarified to collect blood and liver tissues
      for analysis. Tempol pretreatment significantly captured elevated levels of ALT
      and AST activities, lipid peroxidation, total bilirubin and increased total thiol
      and catalase contents. Notably, it significantly reduced the expression of tumor
      necrosis factor-alpha (TNF-alpha), Caspase-3 and endoplasmic reticulum (ER)
      inositol-requiring enzyme 1(IRE1) mRNAs, which is an ER trans membrane sensor
      that activates the unfolded protein response (UPR) to maintain the ER and
      cellular function. CONCLUSION: Pretreatment with Tempol has potential
      hepatoprotective effects against acute liver injury, induced by CCl4, through
      antioxidant and anti-inflammatory activities.

PMID- 27044832
TI  - Protective mechanisms of berberine against experimental autoimmune myocarditis in
      a rat model.
AB  - Berberine, an alkaloid derivative extracted from numerous plants of the general
      Berberis and Coptis, has been reported to have immunomodulatory effects against
      immune-mediated disorders in emerging studies. In this study, the effects of
      berberine and its underlying molecular mechanisms were investigated from the
      myosin-induced myocardial injury in rats. Lewis rats were immunized with porcine
      cardiac myosin to induce experimental autoimmune myocarditis (EAM), treated with
      berberine and specific JAK inhibitor AG490 as a positive control. Our data showed
      that both berberine and AG490 significantly reduced the impaired cardiac function
      and the pathophysiological severity, impeded high levels of anti-cardiac myosin
      antibody of EAM rats. Th17 and Th1 cells as well as their cytokines IL-17 and IFN
      gamma were up-regulated in EAM. However, the excessive increase of Th17/Th1
      responses was restored by berberine and AG490. We also examined the expression
      level of phosphorylated proteins of JAK-STAT pathway which has a key role in the
      Th17 and Th1 lineage commitment. The phosphorylated (p)-STAT1,STAT3 and STAT4
      increased significantly in EAM, while berberine notably attenuated their
      excessive expression. This effect of berberine was equivalent to that of AG490
      blockade. Our current study demonstrated that berberine could ameliorate EAM and
      the underling mechanisms may be due to the fact that berberine differentially
      modulates the activities of p-STAT1, p-STAT3 and p-STAT4 to suppress Th17 and Th1
      cell differentiation. 

PMID- 27044833
TI  - Lupeol acetate ameliorates collagen-induced arthritis and osteoclastogenesis of
      mice through improvement of microenvironment.
AB  - Lupeol has been shown with anti-inflammation and antitumor capability, however,
      the poor bioavailability limiting its applications in living subjects. Lupeol
      acetate (LA), a derivative of lupeol, shows similar biological activities as
      lupeol but with better bioavailability. Here RAW 264.7 cells and bone marrow
      derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) were treated
      with 0-80MUM of LA, and assayed for TNF-alpha, IL-1beta, COX-2, MCP-1 using
      Western blotting. Moreover, osteoclatogenesis was examined with reverse
      transcription PCR (RT-PCR) and tartrate-resistant acid phosphatase (TRAP)
      staining. For in vivo study, collagen-induced arthritis (CIA)-bearing DBA/1J mice
      were randomly separated into three groups: vehicle, LA-treated (50mg/kg) and
      curcumin-treated (100mg/kg). Therapeutic efficacies were assayed by the clinical
      score, expression levels of serum cytokines including TNF-alpha and IL-1beta,
      (18)F-fluorodeoxyglucose ((18)F-FDG) microPET/CT and histopathology. The results
      showed that LA could inhibit the activation, migration, and formation of
      osteoclastogenesis of macrophages in a dose-dependent manner. In RA-bearing mice,
      the expressions of inflammation-related cytokines were suppressed, and clinical
      symptoms and bone erosion were ameliorated by LA. The accumulation of (18)F-FDG
      in the joints of RA-bearing mice was also significantly decreased by LA. The
      results indicate that LA significantly improves the symptoms of RA by down
      regulating expressions of inflammatory cytokines and osteoclastogenesis. 

PMID- 27044834
TI  - Altered E-NTPDase/E-ADA activities and CD39 expression in platelets of sickle
      cell anemia patients.
AB  - Sickle cell anemia (SCA) is a hemoglobinopathy characterized by hemolysis and
      vaso-occlusions caused by rigidly distorted red blood cells. Sickle cell crisis
      is associated with extracellular release of nucleotides and platelets, which are
      critical mediators of hemostasis participating actively in purinergic
      thromboregulatory enzymes system.This study aimed to investigate the activities
      of purinergic system ecto-enzymes present on the platelet surface as well as CD39
      and CD73 expressions on platelets of SCA treated patients. Fifteen SCA treated
      patients and 30 health subjects (control group) were selected. Ecto-nucleoside
      triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-5'-NT) and
      ecto-adenosine deaminase (E-ADA) activities were measured in platelets isolated
      from these individuals. Results demonstrated an increase of 41 % in the E-NTPDase
      for ATP hydrolysis, 52% for ADP hydrolysis and 60 % in the E-ADA activity in SCA
      patients (P<0.05); however, a two folds decrease in the CD39 expression in
      platelets was observed in the same group (P<0.01). The increased E-NTPDase
      activity could be a compensatory mechanism associated with the low expression of
      CD39 in platelets. Besides, alteration of these enzymes activities suggests that
      the purinergic system could be involved in the thromboregulatory process in SCA
      patients. 

PMID- 27044835
TI  - miR-601 is a prognostic marker and suppresses cell growth and invasion by
      targeting PTP4A1 in breast cancer.
AB  - MicroRNAs (miRNA) play important roles in the initiation and progression of
      breast cancer. Here, we investigated the role of miR-601 in breast cancer and
      found that its expression was significantly down-regulated in breast cancer
      tissues compared with matched adjacent non-cancerous breast tissues. Moreover, we
      found that down-regulation of miR-601 was closely associated with distant
      metastasis and poor distant metastasis-free survival in breast cancer. In
      addition, miR-601 levels were inversely correlated with metastatic potential of
      human breast cancer cell lines. Further experiments showed that ectopic
      overexpression of miR-601 suppressed breast cancer cell proliferation, migration
      and invasion, whereas miR-601 knockdown promoted breast cancer cell
      proliferation, migration and invasion. Furthermore, protein tyrosine phosphatase
      type IVA 1 (PTP4A1) was identified as a direct target of miR-601. Overexpression
      of miR-601 repressed PTP4A1 mRNA and protein expression. Conversely, inhibition
      of miR-601 increased PTP4A1 mRNA and protein expression. Taken together, our data
      suggest that miR-601 inhibits growth and invasion of breast cancer cells by
      targeting PTP4A1 and that miR-601 is a potential biomarker for prognosis and
      therapeutic target in breast cancer. 

PMID- 27044836
TI  - Beneficial effects of chlorogenic acid on alcohol-induced damage in PC12 cells.
AB  - As one of the most commonly abused psychotropic substances, ethanol exposure has
      deleterious effects on the central nervous system (CNS). The most detrimental
      results of ethanol exposure during development are the loss of neurons in brain
      regions such as the hippocampus and neocortex, which may be related to the
      apoptosis and necrosis mediated by oxidative stress. Recent studies indicated
      that a number of natural drugs from plants play an important role in protection
      of nerve cells from damage. Among these, it has been reported that chlorogenic
      acid (CA) has neuroprotective effects against oxidative stress. Thus, it may play
      some beneficial effects on ethanol-induced neurotoxicity. However, the effects of
      CA on ethanol-induced nerve damage remain unclear. In order to investigate the
      protective effects of CA on alcohol-induced apoptosis in rat pheochromocytoma
      PC12 cells, in the present study, cell viability and the optimal dosage of CA
      were first quantified by MTT assay. Then, the cell apoptosis and cell cycle were
      respectively investigated by Hoechst 33258 staining and flow cytometer (FCM). To
      further clarify the possible mechanism, followed with the test of mitochondria
      transmembrane potential with Rhodamine 123 (Rho 123) staining, the expression of
      Bcl-2, Capase-3 and growth associated protein-43 (GAP-43) were analyzed by
      immunofluorescence assay separately. The results showed that treatment with 500
      mM alcohol decreased the cell viability and then significantly induced apoptosis
      in PC12 cells. However, when pretreated with different concentrations of CA (1,
      5, 10, 50 MUM), cell viability increased in different degree. Comparatively, CA
      with the concentration of 10 MUM most effectively promoted the proliferation of
      damaged cells, increased the distribution ratio of the cells at the G2/M and S
      phases, and enhanced mitochondria transmembrane potential. This appears to be in
      agreement with up-regulation of the expression of Bcl-2 and GAP-43, and down
      regulation of the expression of Capsae-3. Taken together, CA can increase cell
      viability and promote cell differentiation by preventing alcohol-induced cell
      from apoptosis. The mechanism may be related to the enhancement of the expression
      of GAP-43 and the inhibition of mitochondrial apoptotic pathway including
      promotion of mitochondria transmembrane potential, up-regulation of the
      expression of Bcl-2, and down-regulation of the expression of Capsae-3.

PMID- 27044837
TI  - A possible significant role of zinc and GPR39 zinc sensing receptor in Alzheimer
      disease and epilepsy.
AB  - Zinc the essential trace element, plays a significant role in the brain
      development and in the proper brain functions at every stage of life. Misbalance
      of zinc (Zn(2+)) ions in the central nervous system is involved in the
      pathogenesis of numerous neurodegenerative disorders such as Alzheimer's disease,
      Depression, and Epilepsy. In brain, Zn(2+) has been identified as a ligand,
      capable of activating and inhibiting the receptors including the NMDA-type
      glutamate receptors (NMDARs), GABAA receptors, nicotinic acetylcholine receptors
      (nAChRs), glycine receptors (glyR) and serotonin receptors (5-HT3). Recently
      GPR39 has been identified as a zinc-specific receptor, widely expressed in brain
      tissues including the frontal cortex, amygdala, and hippocampus. GPR39, when
      binding with Zn(2+) has shown promising therapeutic potentials. This review
      presents current knowledge regarding the role of GPR39 zinc sensing receptor in
      brain, with a focus on Alzheimer's disease and Epilepsy. Although the results are
      encouraging, further research is needed to clarify zinc and GPR39 role in the
      treatment of Alzheimer's disease and Epilepsy. 

PMID- 27044838
TI  - Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem
      Resistant Escherichia coli: In Vivo Trials in a Murine Model.
AB  - The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased
      considerably during the last decade, which can be ascribed to relative scarcity
      of effective non toxic antimicrobial agents. The present study was conducted to
      evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of
      Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at
      preclinical level using peritonitis infection model in Sprague Dawley rats.
      Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood
      and urine samples of test animals for a period of 5 days from infection. A
      reduction in microbial count of biological fluids was considered as the primary
      endpoint of the selected murine model. Physical, biochemical, hematological and
      histological indices of toxicity were employed as secondary relative indicators
      of the induced disease. Physical manifestations of infected rats included
      significantly high body temperature (TempInfected=103.18 degrees F, ~5% increase)
      and noteworthy reduction in weight (WeightInfected=126.83g, ~15% decrease) as
      compared to control. Significant (P<0.05) increase in total white blood cells,
      eosinophil and monocyte counts as well as a significant decrease (P<0.05) in
      erythrocytes count, hematocrit volume, red blood cell distribution width and
      hemoglobin concentration were observed in the infected group as compared to the
      control group. Furthermore, noteworthy increase in liver and kidney function test
      parameters were observed in case of infected groups. All the hematological and
      biochemical parameters were found to be within optimum range in case of treatment
      group, indicating restoration of homeostasis. Histopathological studies also
      presented symptoms of hemorrhage and glomerular damage with structural distortion
      in glomerular capillary loops of infected groups, which were later recovered in
      treated groups, indicating the nephro-protective potential of PTRC-31911-A. The
      study clearly points out that Camellia sinensis extract (PTRC-31911-A; single
      dose of 5mg/Kg bwt; oral,+24h) is highly effective against Carbapenem Resistant
      Escherichia coli owing mainly to the presence of flavonoids and polyphenolic
      compounds, identified by LCMS. Ongoing studies are expected to further unravel
      the mechanism of action and bioactivity determinants of this broad spectrum plant
      extract. 

PMID- 27044839
TI  - Discovery of 2-(3,4-dichlorophenoxy)-N-(2-morpholin-4-ylethyl)acetamide: A
      selective sigma1 receptor ligand with antinociceptive effect.
AB  - Compound 2-(3,4-dichlorophenoxy)-N-(2-morpholin-4-ylethyl)acetamide (1) was
      designed, prepared and the in vitro binding evaluation against sigma1 and sigma2
      receptors was measured. Compound 1 showed high sigma1 receptor affinity (Ki=42
      nM) and it was 36-times more selective for sigma1 than sigma2 receptor. Also, it
      was performed a molecular docking of compound 1 into the ligand binding pocket
      homology model of sigma1 receptor, showing a salt bridge between the ionized
      morpholine ring and Asp126, as well as important short contacts with residues
      Tyr120, His154 and Trp164. Ligand efficiency indexes and predicted toxicity
      analysis revealed an excellent intrinsic quality of 1. The antinociceptive effect
      of compound 1 was determined using the formalin test. The ipsilateral local
      peripheral (10-300 MUg/paw) and intrathecal (100 MUg/rat) administration of 1
      produced a reduction in formalin-induced nociception. The in vivo results
      indicated that 1 may be effective in treating inflammatory pain.

PMID- 27044840
TI  - MiR-200b promotes the cell proliferation and metastasis of cervical cancer by
      inhibiting FOXG1.
AB  - BACKGROUND: Previous studies have revealed the important role of miR-200b in
      cancer biology, including its upregulation in cervical cancer. However, miR-200b
      function in cervical cancer progression remains unclear. Thus, this study aims to
      explore the functional role of miR-200b in cervical cancer development, involving
      its potential regulation on FoxG1, one transcriptional repressor. METHODS: Thirty
      paired cervical cancer samples were used to analyze the expression of miR-200b
      and FoxG1 by real time PCR and western blot analysis. Further gain- and loss-of
      function studies were performed to validate FoxG1 as one miR-200b target, in line
      with luciferase report assays. MiR-200b silence was also conducted to observe its
      regulation on cell viability, migration and invasion in vitro, while tumor growth
      in vivo was tracked through the delivery of miR-200b inhibitor. RESULTS: MiR-200b
      upregulation was confirmed in cancer tissues or cells as compared to normal
      controls, while FoxG1 downregulation was observed and then FoxG1 was definitely
      validated as one miR-200b target. Further in vitro studies showed that enforced
      miR-200b downregulation induced the decrease of cell ability, with increased cell
      apoptosis, and attenuated ability of cell migration and invasion in both HeLa and
      C33A cells, while further inhibition of FoxG1 expression could reverse all these
      changes. In addition, miR-200b silence in vivo strongly inhibited tumor growth.
      CONCLUSION: Upregulated miR-200b in cervical cancer was proven to show positive
      regulation on cervical cancer development by directly targeting FoxG1. Moreover,
      miR-200b silence was proposed to inhibit tumor growth in vivo, implying its
      therapeutic value in cervical cancer treatment.

PMID- 27044841
TI  - Nitric oxide levels in HIV-infected, untreated patients and HIV-infected patients
      receiving antiretroviral therapy.
AB  - The role of nitric oxide (NO) in HIV infection is ambiguous; controversy exists
      around whether the levels of serum NO are increased or decreased in HIV-infected
      patients. Thus, it is necessary to reassess NO levels in HIV-infected patients.
      The aim of this study was to investigate the nitrite/nitrate metabolite (NOx)
      levels in HIV-infected untreated patients and in HIV-infected patients receiving
      highly active antiretroviral therapy (HAART), compared with HIV-uninfected
      individuals (control group). The HIV-infected patients enrolled in this study had
      been receiving HAART for at least 6 months (HIV-treated) or had not received
      HAART for at least 6 months (HIV-untreated group). New recommendations encourage
      initiating treatment in HIV-infected adults at a CD4 cell count of 500
      cells/mm(3) or less. We also investigated whether levels of NOx were associated
      with immunophenotypic characteristic of HIV-infected patients. Our results showed
      a statistically significant increase in NOx levels in the HIV-untreated group
      (164.0 +/- 166.6 MUmol/L), compared with both the control (98.9 +/- 59.4 MUmol/L)
      and HIV-treated group (71.7 +/- 53.3 MUmol/L). Multiple regression analysis
      showed that the differences in NOx level were independent of gender, liver enzyme
      level, lipid measurement, and hematological parameters. In addition, a lower
      CD4/CD8 ratio was associated with higher NOx levels in HIV-infected patients. The
      results further revealed that NOx levels were increased in HIV infection, and
      that derangement of immune system function was associated with increased NO
      levels. The levels of NOx were found to decline with the use of HAART, which may
      contribute to cardiovascular disease in HIV-infected patients.

PMID- 27044842
TI  - The novel anthraquinone derivative IMP1338 induces death of human cancer cells by
      p53-independent S and G2/M cell cycle arrest.
AB  - To identify novel small molecules that induce selective cancer cell death, we
      screened a chemical library containing 1040 compounds in HT29 colon cancer and
      CCD18-Co normal colon cells, using a phenotypic cell-based viability assay system
      with the Cell Counting Kit-8 (CCK-8). We discovered a novel anthraquinone
      derivative, N-(4-[{(9,10-dioxo-9,10-dihydro-1-anthracenyl)sulfonyl}amino]phenyl)
      N-methylacetamide (IMP1338), which was cytotoxic against the human colon cancer
      cells tested. The MTT cell viability assay showed that treatment with IMP1338
      selectively inhibited HCT116, HCT116 p53(-/-), HT29, and A549 cancer cell
      proliferation compared to that of Beas2B normal epithelial cells. To elucidate
      the cellular mechanism underlying the cytotoxicity of IMP1338, we examined the
      effect of IMP1338 on the cell cycle distribution and death of cancer cells.
      IMP1338 treatment significantly arrested the cell cycle at S and G2/M phases by
      DNA damage and led to apoptotic cell death, which was determined using FACS
      analysis with Annexin V/PI double staining. Furthermore, IMP1338 increased
      caspase-3 cleavage in wild-type p53, p53 knockout HCT116, and HT29 cells as
      determined using immunoblotting. In addition, IMP1338 markedly induced the
      phosphorylation of histone H2AX and Chk1 in both cell lines while the combination
      of 5-fluorouracil (5-FU) and radiation inhibited the viability of HCT116, HCT116
      p53(-/-), and HT29 cells compared to 5-FU or radiation alone. Our findings
      indicated that IMP1338 induced p53-independent cell death through S and G2/M
      phase arrest as well as DNA damage. These results provide a basis for future
      investigations assessing the promising anticancer properties of IMP1338. 

PMID- 27044843
TI  - MiR-1180 promoted the proliferation of hepatocellular carcinoma cells by
      repressing TNIP2 expression.
AB  - MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional
      regulatory function, playing crucial roles in cancer development and progression
      of hepatocellular carcinoma (HCC). Previous studies have indicated that miR-1180
      was implicated in diverse biological processes. However, the underlying mechanism
      of miR-1180 in HCC has not been intensively investigated. In this study, we aimed
      to investigate the role of miR-1180 and its target genes in HCC. We found that
      miR-1180 expression was significantly increased in HCC cells and clinical tissues
      compared with their corresponding controls. Overexpression of miR-1180 promoted
      cell proliferation in HCC cell line HepG2. TNFAIP3 interacting protein 2 (TNIP2),
      a potential target gene of miR-1180, and were validated by a luciferase assay.
      Further studies revealed that miR-1180 regulated cell proliferation of HCC by
      directly suppressing TNIP2 expression and the knockdown of TNIP2 expression
      reversed the effect of miR-1180-in on HCC cell proliferation. In summary, our
      data indicated that miR-1180 might act as a tumor promoter by targeting TNIP2
      during development of HCC. 

PMID- 27044844
TI  - Effect of antiretroviral therapy in thromboregulation through the hydrolysis of
      adenine nucleotides in platelets of HIV patients.
AB  - The human immunodeficiency virus (HIV) infection results in biochemical and
      vascular dysfunctions. The highly active antiretroviral therapy (HAART) markedly
      reduces mortality and opportunistic diseases associated with acquired
      immunodeficiency syndrome (AIDS). This increased survival time predisposes the
      development of cardiovascular diseases. Platelets present purinergic system
      ectoenzymes such as E-NTPDase, E-5'-nucleotidase and E-ADA on its surface. In
      view of this, the aim of this study was to evaluate the activity of these
      ectoenzymes in platelets as well as the platelet aggregation and lipid profile of
      patients with HIV infection and also patients receiving HAART. The results showed
      an increase in the E-NTPDase activity for ATP hydrolysis in the HIV group
      compared with the control group and the HIV/HAART group. When assessing the
      activity E-NTPDase hydrolysis to ADP, the results revealed an increase in
      activity in the HIV group when compared to the control group, and a decrease in
      activity when in the HIV/HAART group when compared to the control and HIV groups.
      The activity of E-5'-nucleotidase revealed an increase in AMP hydrolysis in the
      HIV group, as the results from control and HIV/HAART groups showed no statistical
      difference. Regarding the E-ADA activity, the HIV and HIV/HAART groups revealed a
      decreased deamination of adenosine when compared with the control group.
      Furthermore, we observed an increased platelet aggregation of HIV/HAART group
      compared with the control group. Thus, our results suggest that antiretroviral
      treatment against HIV has a significant effect on the activity of purinergic
      system ectoenzymes demonstrating that thromboregulation is involved in the
      process. 

PMID- 27044845
TI  - Brain activity during arithmetic in symbolic and non-symbolic formats in 9-12
      year old children.
AB  - People process numbers in different formats, such as dot arrays (non-symbolic),
      Arabic digits and number words (symbolic), and use these representations when
      performing arithmetic calculations. It remains, however, unclear if and how these
      various presentation formats affect brain activity during arithmetic. We
      conducted an fMRI study in 23 typically developing children aged 9-12. The
      children were asked to subtract numbers up to 10 and had to compare the result to
      a reference number. Numbers were presented in non-symbolic (dot arrays), as well
      as symbolic formats (Arabic digits and number words). Our findings suggest that
      similar brain networks are recruited during arithmetic with different symbolic
      formats, i.e. Arabic digits and number words. On the other hand, there are clear
      differences between calculating with symbolic and non-symbolic formats.
      Specifically, calculating in symbolic formats showed increased activity in
      angular and supramarginal gyri, whereas arithmetic in the non-symbolic format
      showed increased activity in middle occipital and superior parietal lobes, as
      well as in superior frontal gyrus and insula. These differences in brain activity
      might be explained by differences in the strategies used to solve these
      arithmetic problems.

PMID- 27044847
TI  - On-Chip Micro-Electro-Mechanical System Fourier Transform Infrared (MEMS FT-IR)
      Spectrometer-Based Gas Sensing.
AB  - In this work, we study the detection of acetylene (C2H2), carbon dioxide (CO2)
      and water vapor (H2O) gases in the near-infrared (NIR) range using an on-chip
      silicon micro-electro-mechanical system (MEMS) Fourier transform infrared (FT-IR)
      spectrometer in the wavelength range 1300-2500 nm (4000-7692 cm(-1)). The
      spectrometer core engine is a scanning Michelson interferometer micro-fabricated
      using a deep-etching technology producing self-aligned components. The light is
      free-space propagating in-plane with respect to the silicon chip substrate. The
      moving mirror of the interferometer is driven by a relatively large stroke
      electrostatic comb-drive actuator corresponding to about 30 cm(-1) resolution.
      Multi-mode optical fibers are used to connect light between the wideband light
      source, the interferometer, the 10 cm gas cell, and the optical detector. A wide
      dynamic range of gas concentration down to 2000 parts per million (ppm) in only
      10 cm length gas cell is demonstrated. Extending the wavelength range to the mid
      infrared (MIR) range up to 4200 nm (2380 cm(-1)) is also experimentally
      demonstrated, for the first time, using a bulk micro-machined on-chip MEMS FT-IR
      spectrometer. The obtained results open the door for an on-chip optical gas
      sensor for many applications including environmental sensing and industrial
      process control in the NIR/MIR spectral ranges.

PMID- 27044848
TI  - Suitability of Transportable EDXRF for the On-site Assessment of Ancient Silver
      Coins and Other Silver Artifacts.
AB  - Transportable energy dispersive X-ray fluorescence (XRF) spectrometers allow the
      elemental composition of coins to be measured at collections, enhancing security
      while maximizing access to historically important material. We assessed 10 silver
      coins, using five XRF spectrometers. We found no systematic differences between
      analyses using Mo- and Rh-anode tubes, and no substantial advantage using He
      flush over air for elements heavier than Ti. Higher voltage X-ray tubes enhanced
      analytical precision. Understanding patina composition made a numerical
      correction possible, allowing an approximation of the underlying coin metal with
      good results for metals including Cu, Ag, Au, Pb, and Bi.

PMID- 27044849
TI  - mHealth in psychiatry: time for methodological change.
AB  - A multitude of mental health apps are available to consumers through the Apple
      and Google app stores. However, evidence supporting the effectiveness of mHealth
      is scant. We argue this gap between app availability and research evidence is
      primarily due to unsuitable knowledge translation practices and therefore suggest
      abandoning the randomised controlled trial as the primary app evaluation
      paradigm. Alternative evaluation methodologies such as iterative participatory
      research and single case designs are better aligned with mHealth translational
      needs. A further challenge to the use of mobile technology in mental health is
      the dissemination of information about app quality to consumers. Strategies to
      facilitate successful dissemination of quality resources must consider several
      factors, such as target audience and context. In practice, structured solutions
      to inform consumers of evidence-informed apps could range from the development of
      consumer used tools to app accreditation portals. Consumer enthusiasm for apps
      represents an opportunity to increase access and support for psychiatric
      populations. However, adoption of alternative research methodologies and the
      development of dissemination strategies are vital before this opportunity can be
      substantially seized.

PMID- 27044850
TI  - Effect of hemorrhage rate on early hemodynamic responses in conscious sheep.
AB  - Physiological compensatory mechanisms can mask the extent of hemorrhage in
      conscious mammals, which can be further complicated by individual tolerance and
      variations in hemorrhage onset and duration. We assessed the effect of hemorrhage
      rate on tolerance and early physiologic responses to hemorrhage in conscious
      sheep. Eight Merino ewes (37.4 +/- 1.1 kg) were subjected to fast (1.25
      mL/kg/min) and slow (0.25 mL/kg/min) hemorrhages separated by at least 3 days.
      Blood was withdrawn until a drop in mean arterial pressure (MAP) of >30 mmHg and
      returned at the end of the experiment. Continuous monitoring includedMAP, central
      venous pressure, pulmonary artery pressure, pulse oximetry, and tissue oximetry.
      Cardiac output by thermodilution and arterial blood samples were also measured.
      The effects of fast versus slow hemorrhage rates were compared for total volume
      of blood removed and stoppage time (whenMAP < 30 mmHg of baseline) and
      physiological responses during and after the hemorrhage. Estimated blood volume
      removed whenMAPdropped 30 mmHg was 27.0 +/- 4.2% (mean +/- standard error) in the
      slow and 27.3 +/- 3.2% in the fast hemorrhage (P = 0.47, pairedttest between
      rates). Pressure and tissue oximetry responses were similar between hemorrhage
      rates. Heart rate increased at earlier levels of blood loss during the fast
      hemorrhage, but hemorrhage rate was not a significant factor for individual
      hemorrhage tolerance or hemodynamic responses. In 5/16 hemorrhages MAP stopping
      criteria was reached with <25% of blood volume removed. This study presents the
      physiological responses leading up to a significant drop in blood pressure in a
      large conscious animal model and how they are altered by the rate of hemorrhage. 

PMID- 27044851
TI  - Short-duration intermittent hypoxia enhances endurance capacity by improving
      muscle fatty acid metabolism in mice.
AB  - This study was designed to (1) investigate the effects of acute short-duration
      intermittent hypoxia on musclemRNAand microRNAexpression levels; and (2) clarify
      the mechanisms by which short-duration intermittent hypoxia improves endurance
      capacity. Experiment-1: Male mice were subjected to either acute 1-h hypoxia (12%
      O2), acute short-duration intermittent hypoxia (12% O2for 15 min, room air for 10
      min, 4 times, Int-Hypo), or acute endurance exercise (Ex). The expression of
      vascular endothelial growth factor-AmRNAwas significantly greater than the
      control at 0 h post Ex and 6 h post Int-Hypo in the deep red region of the
      gastrocnemius muscle. miR-16 expression levels were significantly lower at 6 and
      10 h post Int-Hypo. Peroxisome proliferator-activated receptor gamma coactivator
      1-alpha (PGC-1alpha)mRNAlevels were significantly greater than the control at 3 h
      post Ex and 6 h post Int-Hypo. miR-23a expression levels were lower than the
      control at 6-24 h post Int-Hypo. Experiment-2: Mice were subjected to normoxic
      exercise training with or without intermittent hypoxia for 3 weeks. Increases in
      maximal exercise capacity were significantly greater by training with short
      duration intermittent hypoxia (IntTr) than without hypoxia. Both 3-Hydroxyacyl
      CoA-dehydrogenase and total carnitine palmitoyl transferase activities were
      significantly enhanced in IntTr. Peroxisome proliferator-activated receptor delta
      andPGC-1alpha mRNAlevels were both significantly greater in IntTr than in the
      sedentary controls. These results suggest that exercise training under normoxic
      conditions with exposure to short-duration intermittent hypoxia represents a
      beneficial strategy for increasing endurance performance by enhancing fatty acid
      metabolism in skeletal muscle. 

PMID- 27044852
TI  - A normalized contrast-encoding model exhibits bright/dark asymmetries similar to
      early visual neurons.
AB  - Biological sensory systems share a number of organizing principles. One such
      principle is the formation of parallel streams. In the visual system, information
      about bright and dark features is largely conveyed via two separate streams:
      theONandOFFpathways. While brightness and darkness can be considered symmetric
      and opposite forms of visual contrast, the response properties of cells in
      theONandOFFpathways are decidedly asymmetric. Here, we ask whether a simple
      contrast-encoding model predicts asymmetries for brights and darks that are
      similar to the asymmetries found in theONandOFFpathways. Importantly, this model
      does not include any explicit differences in how the visual system represents
      brights and darks, but it does include a common normalization mechanism. The
      phenomena captured by the model include (1) nonlinear contrast response
      functions, (2) greater nonlinearities in the responses to darks, and (3) larger
      responses to dark contrasts. We report a direct, quantitative comparison between
      these model predictions and previously published electrophysiological
      measurements from the retina and thalamus (guinea pig and cat, respectively).
      This work suggests that the simple computation of visual contrast may account for
      a range of early visual processing nonlinearities. Assessing explicit models of
      sensory representations is essential for understanding which features of neuronal
      activity these models can and cannot predict, and for investigating how early
      computations may reverberate through the sensory pathways. 

PMID- 27044853
TI  - Maximal exercise does not increase ventilation heterogeneity in healthy trained
      adults.
AB  - The effect of exercise on ventilation heterogeneity has not been investigated. We
      hypothesized that a maximal exercise bout would increase ventilation
      heterogeneity. We also hypothesized that increased ventilation heterogeneity
      would be associated with exercise-induced arterial hypoxemia (EIAH). Healthy
      trained adult males were prospectively assessed for ventilation heterogeneity
      using lung clearance index (LCI), Scond, and Sacinat baseline, postexercise and
      at recovery, using the multiple breath nitrogen washout technique. The maximal
      exercise bout consisted of a maximal, incremental cardiopulmonary exercise test
      at 25 watt increments. Eighteen subjects were recruited with mean +/- SDage of 35
      +/- 9 years. There were no significant changes inLCI, Scond, or Sacinfollowing
      exercise or at recovery. While there was an overall reduction in SpO2with
      exercise (99.3 +/- 1 to 93.7 +/- 3%,P < 0.0001), the reduction in SpO2was not
      associated with changes inLCI, Scondor Sacin Ventilation heterogeneity is not
      increased following a maximal exercise bout in healthy trained adults.
      Furthermore,EIAHis not associated with changes in ventilation heterogeneity in
      healthy trained adults. 

PMID- 27044854
TI  - Acute supplementation of N-acetylcysteine does not affect muscle blood flow and
      oxygenation characteristics during handgrip exercise.
AB  - N-acetylcysteine (NAC; antioxidant and thiol donor) supplementation has improved
      exercise performance and delayed fatigue, but the underlying mechanisms are
      unknown. One possibility isNACsupplementation increases limb blood flow during
      severe-intensity exercise. The purpose was to determine ifNACsupplementation
      affected exercising arm blood flow and muscle oxygenation characteristics. We
      hypothesized thatNACwould lead to higher limb blood flow and lower muscle
      deoxygenation characteristics during severe-intensity exercise. Eight healthy
      nonendurance trained men (21.8 +/- 1.2 years) were recruited and completed two
      constant power handgrip exercise tests at 80% peak power until exhaustion.
      Subjects orally consumed either placebo (PLA) orNAC(70 mg/kg) 60 min prior to
      handgrip exercise. Immediately prior to exercise, venous blood samples were
      collected for determination of plasma redox balance. Brachial artery blood flow
      (BABF) was measured via Doppler ultrasound and flexor digitorum superficialis
      oxygenation characteristics were measured via near-infrared spectroscopy.
      FollowingNACsupplementaiton, plasma cysteine (NAC: 47.2 +/- 20.3 MUmol/L vs.PLA:
      9.6 +/- 1.2 MUmol/L;P = 0.001) and total cysteine (NAC: 156.2 +/- 33.9 MUmol/L
      vs.PLA: 132.2 +/- 16.3 MUmol/L;P = 0.048) increased. Time to exhaustion was not
      significantly different (P = 0.55) betweenNAC(473.0 +/- 62.1 sec) andPLA(438.7 +/
      58.1 sec). RestingBABFwas not different (P = 0.79) withNAC(99.3 +/- 31.1 mL/min)
      andPLA(108.3 +/- 46.0 mL/min).BABFwas not different (P = 0.42) during exercise or
      at end-exercise (NAC: 413 +/- 109 mL/min;PLA: 445 +/- 147 mL/min). Deoxy
      [hemoglobin+myoglobin] and total-[hemoglobin+myoglobin] were not significantly
      different (P = 0.73 andP = 0.54, respectively) at rest or during exercise between
      conditions. We conclude that acuteNACsupplementation does not alter oxygen
      delivery during exercise in men. 

PMID- 27044855
TI  - The predictive value of echocardiography for chronic thromboembolic pulmonary
      hypertension after acute pulmonary embolism in Korea.
AB  - BACKGROUND/AIMS: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life
      threatening complication after acute pulmonary embolism (APE) and is associated
      with substantial morbidity and mortality. This study aimed to investigate the
      incidence of CTEPH after APE in Korea and to determine echocardiographic
      predictors of CTEPH. METHODS: Among 381 patients with APE confirmed by chest
      computed tomography (CT) between January 2007 and July 2013, 246 consecutive
      patients with available echocardiographic data were enrolled in this study. CTEPH
      was defined as a persistent right ventricular systolic pressure (RVSP) greater
      than 35 mmHg on echocardiography during follow-up and persistent pulmonary
      embolism on the follow-up CT. RESULTS: Fifteen patients (6.1%) had CTEPH. The
      rate of right ventricular (RV) dilatation (66.7% vs. 28.1%, p = 0.002) and the
      RVSP (75.5 mmHg vs. 39.0 mmHg, p < 0.001) were significantly higher in the CTEPH
      group. D-dimers, RV dilatation, RV hypertrophy, RVSP, and intermediate-risk APE
      were associated with the risk of CTEPH after APE (odds ratio [OR] 0.59, 5.11,
      7.82, 1.06, and 4.86, respectively) on univariate analysis. RVSP remained as a
      significant predictor of CTEPH on multivariate analysis (OR, 1.056; 95%
      confidence interval, 1.006 to 1.109; p = 0.029). CONCLUSIONS: This study showed
      that the incidence of CTEPH after APE in Korea was 6.1% and that initial RVSP by
      echocardiography was a strong prognostic factor for CTEPH.

PMID- 27044856
TI  - Ultrasound-guided percutaneous portal transplantation of peripheral blood
      monocytes in patients with liver cirrhosis.
AB  - BACKGROUND/AIMS: Liver transplantation offers the only definite cure for
      cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this
      setting. In this study, we aimed to explore the safety and efficacy of ultrasound
      guided percutaneous portal transplantation of peripheral blood monocyte cell
      (PBMC) in cirrhotic patients. METHODS: A total of nine decompensated cirrhotic
      patients were randomized into three groups: group 1 (n = 3) was control group,
      group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF)
      mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by
      leukapheresis and PBMC transplantation through ultrasound-guided percutaneous
      portal vein puncture. Liver function and clinical features were evaluated.
      RESULTS: At baseline, the Child-Turcotte-Pugh and the model for end-stage liver
      disease scores were comparable in study groups. Compared with group 1, there was
      a tendency to improve liver function in group 3 at 6 months after treatment.
      Treatment was tolerable and no complications were encountered related to the G
      CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies
      showed patent portal veins at the end of the study period. CONCLUSIONS:
      Autologous PBMC transplantation through ultrasound-guided percutaneous portal
      vein puncture could be considered as a safe alternative treatment for
      decompensated cirrhotic patients.

PMID- 27044857
TI  - The impact of high serum bicarbonate levels on mortality in hemodialysis
      patients.
AB  - BACKGROUND/AIMS: The optimal serum bicarbonate level is controversial for
      patients who are undergoing hemodialysis (HD). In this study, we analyzed the
      impact of serum bicarbonate levels on mortality among HD patients. METHODS:
      Prevalent HD patients were selected from the Clinical Research Center registry
      for End Stage Renal Disease cohort in Korea. Patients were categorized into
      quartiles according to their total carbon dioxide (tCO2) levels: quartile 1, a
      tCO2 of < 19.4 mEq/L; quartile 2, a tCO2 of 19.4 to 21.5 mEq/L; quartile 3, a
      tCO2 of 21.6 to 23.9 mEq/L; and quartile 4, a tCO2 of >= 24 mEq/L. Cox regression
      analysis was used to calculate the adjusted hazard ratio (HR) and confidence
      interval (CI) for mortality. RESULTS: We included 1,159 prevalent HD patients,
      with a median follow-up period of 37 months. Kaplan-Meier analysis revealed that
      the all-cause mortality was significantly higher in patients from quartile 4,
      compared to those from the other quartiles (p = 0.009, log-rank test). The
      multivariate Cox proportional hazard model revealed that patients from quartile 4
      had significantly higher risk of mortality than those from quartile 1, 2 and 3,
      after adjusting for the clinical variables in model 1 (HR, 1.99; 95% CI, 1.15 to
      3.45; p = 0.01) and model 2 (HR, 1.82; 95% CI, 1.03 to 3.22; p = 0.04).
      CONCLUSIONS: Our data indicate that high serum bicarbonate levels (a tCO2 of >=
      24 mEq/L) were associated with increased mortality among prevalent HD patients.
      Further effort might be necessary in finding the cause and correcting metabolic
      alkalosis in the chronic HD patients with high serum bicarbonate levels.

PMID- 27044859
TI  - The clinical management of hyponatraemia.
AB  - Hyponatraemia is the most common electrolyte disorder seen in clinical practice
      and the consequences can range from minor symptoms to life-threatening
      complications including seizures and cardiorespiratory distress. These effects
      occur as a result of fluid shifts due to deranged serum tonicity and subsequent
      cerebral oedema. The appropriate assessment and management of patients with
      hyponatraemia is not always achieved in clinical practice, which is partly
      related to challenges in teaching with limited clinical guidance. Recently, the
      European Society of Endocrinology, European Society of Intensive Care Medicine
      and European Renal Association-European Dialysis and Transplant Association
      produced clinical practice guidelines to focus on appropriate investigation and
      management of these patients. Within this manuscript, we highlight the key points
      from these guidelines, which are most pertinent to doctors of all specialties to
      improve the care of patients with this common electrolyte disorder. 

PMID- 27044858
TI  - Chronic lymphocytic leukemia: a clinical review including Korean cohorts.
AB  - Only 5th decade ago, chronic lymphocytic leukemia (CLL) was only recognized as
      disease group of presenting features like peripheral lymphocytosis, organomegaly
      including of splenomegaly. As understanding of disease biology and molecular
      diagnostic tools are getting improved gradually, characterization of variation in
      CLL's clinical courses was facilitated, resulting in better risk stratification
      and targeted treatments. Consequently multiple new targeted agents have been used
      in treatment of CLL, it makes improved clinical outcome. Rituximab containing
      chemoimmunotherapy (combination of rituximab, fludarabine, and cyclophosphamide)
      have shown better overall response rate and progression-free survival on fit
      patients' group in front-line setting, result in standard first-line therapeutic
      option for CLL. Furthermore, after introducing that the B-cell receptor is
      crucial for the evolution and progression of CLL, emerging treatments targeting
      highly activated surface antigens and oncogenic signaling pathways have been
      associated with several successes in recent decades. These include new anti-CD 20
      monoclonal antibody (obinutuzumab), the bruton tyrosine kinase inhibitor
      (ibrutinib), the phosphatidylinositol 3-kinase inhibitor (idelalisib), and B-cell
      CLL/lymphoma 2 inhibitor (ABT-199 and ABT-263). So, we discuss not only general
      pathophysiology of CLL, but also rapidly advancing treatment strategies that are
      being studied or approved for treatment of CLL. 

PMID- 27044860
TI  - Teaching M&M rounds skills: enhancing and assessing patient safety competencies
      using the Ottawa M&M model.
AB  - BACKGROUND: Postgraduate medical education bodies and national patient safety
      institutes recommend that trainees develop patient safety competencies such as
      those for Morbidity and Mortality (M&M) rounds, yet there exists no model for
      their educational delivery. OBJECTIVE: We studied the effect of a single
      educational intervention on emergency medicine residents' aptitudes in selecting
      and analysing M&M rounds cases. METHODS: In this before-and-after study,
      participants attended an 1 h educational session based on the previously
      described Ottawa Morbidity and Mortality Model (OM3). Residents were asked to
      submit a case suitable for M&M rounds both preintervention and postintervention.
      A novel M&M rounds case critique tool was developed based on OM3 and used to
      assign a numerical score to each submitted case. Our primary outcome was an
      increase in mean scores between phases using the case critique tool. An a priori
      score increase of 1 was defined as educationally significant. Data were analysed
      using a paired Student's t test. RESULTS: A total of 19 residents were recruited
      for our pre-intervention and 15 residents for the post-intervention analysis.
      Mean M&M rounds case critique scores increased from 5.53 to 8.67 (p<0.01) between
      phases. Residents reported higher comfort with structured case selection and
      analysis, with an increase in five-point Likert scale means of 2.32 and 3.69
      (p<0.01). CONCLUSIONS: We found that residents were more effective at M&M rounds
      case selection and analysis after our focused 1 h educational intervention.
      Training programmes should consider an M&M rounds training model to ensure future
      physicians have these skills for 21st-century practice.

PMID- 27044861
TI  - Preadipocyte factor 1 induces pancreatic ductal cell differentiation into insulin
      producing cells.
AB  - The preadipocyte factor 1 (Pref-1) is involved in the proliferation and
      differentiation of various precursor cells. However, the intracellular signaling
      pathways that control these processes and the role of Pref-1 in the pancreas
      remain poorly understood. Here, we showed that Pref-1 induces insulin synthesis
      and secretion via two independent pathways. The overexpression of Pref-1
      activated MAPK signaling, which induced nucleocytoplasmic translocation of FOXO1
      and PDX1 and led to the differentiation of human pancreatic ductal cells into
      beta-like cells and an increase in insulin synthesis. Concurrently, Pref-1
      activated Akt signaling and facilitated insulin secretion. A proteomics analysis
      identified the Rab43 GTPase-activating protein as a downstream target of Akt. A
      serial activation of both proteins induced various granular protein syntheses
      which led to enhanced glucose-stimulated insulin secretion. In a
      pancreatectomised diabetic animal model, exogenous Pref-1 improved glucose
      homeostasis by accelerating pancreatic ductal and beta-cell regeneration after
      injury. These data establish a novel role for Pref-1, opening the possibility of
      applying this molecule to the treatment of diabetes. 

PMID- 27044862
TI  - Large-scale Growth and Simultaneous Doping of Molybdenum Disulfide Nanosheets.
AB  - A facile method that uses chemical vapor deposition (CVD) for the simultaneous
      growth and doping of large-scale molybdenum disulfide (MoS2) nanosheets was
      developed. We employed metalloporphyrin as a seeding promoter layer for the
      uniform growth of MoS2 nanosheets. Here, a hybrid deposition system that combines
      thermal evaporation and atomic layer deposition (ALD) was utilized to prepare the
      promoter. The doping effect of the promoter was verified by X-ray photoelectron
      spectroscopy and Raman spectroscopy. In addition, the carrier density of the MoS2
      nanosheets was manipulated by adjusting the thickness of the metalloporphyrin
      promoter layers, which allowed the electrical conductivity in MoS2 to be
      manipulated. 

PMID- 27044863
TI  - Structural Analysis of the Myo1c and Neph1 Complex Provides Insight into the
      Intracellular Movement of Neph1.
AB  - The Myo1c motor functions as a cargo transporter supporting various cellular
      events, including vesicular trafficking, cell migration, and stereociliary
      movements of hair cells. Although its partial crystal structures were recently
      described, the structural details of its interaction with cargo proteins remain
      unknown. This study presents the first structural demonstration of a cargo
      protein, Neph1, attached to Myo1c, providing novel insights into the role of
      Myo1c in intracellular movements of this critical slit diaphragm protein. Using
      small angle X-ray scattering studies, models of predominant solution conformation
      of unliganded full-length Myo1c and Myo1c bound to Neph1 were constructed. The
      resulting structures show an extended S-shaped Myo1c with Neph1 attached to its C
      terminal tail. Importantly, binding of Neph1 did not induce a significant shape
      change in Myo1c, indicating this as a spontaneous process or event. Analysis of
      interaction surfaces led to the identification of a critical residue in Neph1
      involved in binding to Myo1c. Indeed, a point mutant from this site abolished
      interaction between Neph1 and Myo1c when tested in the in vitro and in live-cell
      binding assays. Live-cell imaging, including fluorescence recovery after
      photobleaching, provided further support for the role of Myo1c in intracellular
      vesicular movement of Neph1 and its turnover at the membrane.

PMID- 27044864
TI  - Nrf2-Mediated Regulation of Skeletal Muscle Glycogen Metabolism.
AB  - Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose
      homeostasis in vivo Nrf2 suppresses blood glucose levels by protecting pancreatic
      beta cells from oxidative stress and improving peripheral tissue glucose
      utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to
      the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)
      specific Keap1 knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM
      and then examined Nrf2 target gene expression in that tissue. In Keap1MuKO mice,
      blood glucose levels were significantly downregulated and the levels of the
      glycogen branching enzyme (Gbe1) and muscle-type PhKalpha subunit (Phka1) mRNAs,
      along with those of the glycogen branching enzyme (GBE) and the phosphorylase b
      kinase alpha subunit (PhKalpha) protein, were significantly upregulated in mouse
      SkM. Consistent with this result, chemical Nrf2 inducers promoted Gbe1 and Phka1
      mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin
      immunoprecipitation analysis demonstrated that Nrf2 binds the Gbe1 and Phka1
      upstream promoter regions. In Keap1MuKO mice, muscle glycogen content was
      strongly reduced and forced GBE expression in C2C12 myotubes promoted glucose
      uptake. Therefore, our results demonstrate that Nrf2 induction in SkM increases
      GBE and PhKalpha expression and reduces muscle glycogen content, resulting in
      improved glucose tolerance. Our results also indicate that Nrf2 differentially
      regulates glycogen metabolism in SkM and the liver.

PMID- 27044865
TI  - Fine-Tuning of FACT by the Ubiquitin Proteasome System in Regulation of
      Transcriptional Elongation.
AB  - FACT (facilitates chromatin transcription), an evolutionarily conserved histone
      chaperone involved in transcription and other DNA transactions, is upregulated in
      cancers, and its downregulation is associated with cellular death. However, it is
      not clearly understood how FACT is fine-tuned for normal cellular functions.
      Here, we show that the FACT subunit Spt16 is ubiquitylated by San1 (an E3
      ubiquitin ligase) and degraded by the 26S proteasome. Enhanced abundance of Spt16
      in the absence of San1 impairs transcriptional elongation. Likewise, decreased
      abundance of Spt16 also reduces transcription. Thus, an optimal level of Spt16 is
      required for efficient transcriptional elongation, which is maintained by San1
      via ubiquitylation and proteasomal degradation. Consistently, San1 associates
      with the coding sequences of active genes to regulate Spt16's abundance. Further,
      we found that enhanced abundance of Spt16 in the absence of San1 impairs
      chromatin reassembly at the coding sequence, similarly to the results seen
      following inactivation of Spt16. Efficient chromatin reassembly enhances the
      fidelity of transcriptional elongation. Taken together, our results demonstrate
      for the first time a fine-tuning of FACT by a ubiquitin proteasome system in
      promoting chromatin reassembly in the wake of elongating RNA polymerase II and
      transcriptional elongation, thus revealing novel regulatory mechanisms of gene
      expression.

PMID- 27044866
TI  - Determination of a Comprehensive Alternative Splicing Regulatory Network and
      Combinatorial Regulation by Key Factors during the Epithelial-to-Mesenchymal
      Transition.
AB  - The epithelial-to-mesenchymal transition (EMT) is an essential biological process
      during embryonic development that is also implicated in cancer metastasis. While
      the transcriptional regulation of EMT has been well studied, the role of
      alternative splicing (AS) regulation in EMT remains relatively uncharacterized.
      We previously showed that the epithelial cell-type-specific proteins epithelial
      splicing regulatory proteins 1 (ESRP1) and ESRP2 are important for the regulation
      of many AS events that are altered during EMT. However, the contributions of the
      ESRPs and other splicing regulators to the AS regulatory network in EMT require
      further investigation. Here, we used a robust in vitro EMT model to
      comprehensively characterize splicing switches during EMT in a temporal manner.
      These investigations revealed that the ESRPs are the major regulators of some but
      not all AS events during EMT. We determined that the splicing factor RBM47 is
      downregulated during EMT and also regulates numerous transcripts that switch
      splicing during EMT. We also determined that Quaking (QKI) broadly promotes
      mesenchymal splicing patterns. Our study highlights the broad role of
      posttranscriptional regulation during the EMT and the important role of
      combinatorial regulation by different splicing factors to fine tune gene
      expression programs during these physiological and developmental transitions.

PMID- 27044867
TI  - Janus Kinase 1 Is Essential for Inflammatory Cytokine Signaling and Mammary Gland
      Remodeling.
AB  - Despite a wealth of knowledge about the significance of individual signal
      transducers and activators of transcription (STATs), essential functions of their
      upstream Janus kinases (JAKs) during postnatal development are less well defined.
      Using a novel mammary gland-specific JAK1 knockout model, we demonstrate here
      that this tyrosine kinase is essential for the activation of STAT1, STAT3, and
      STAT6 in the mammary epithelium. The loss of JAK1 uncouples interleukin-6-class
      ligands from their downstream effector, STAT3, which leads to the decreased
      expression of STAT3 target genes that are associated with the acute-phase
      response, inflammation, and wound healing. Consequently, JAK1-deficient mice
      exhibit impaired apoptosis and a significant delay in mammary gland remodeling.
      Using RNA sequencing, we identified several new JAK1 target genes that are
      upregulated during involution. These include Bmf and Bim, which are known
      regulators of programmed cell death. Using a BMF/BIM-double-knockout epithelial
      transplant model, we further validated that the synergistic action of these
      proapoptotic JAK1 targets is obligatory for the remodeling of the mammary
      epithelium. The collective results of this study suggest that JAK1 has
      nonredundant roles in the activation of particular STAT proteins and this
      tyrosine kinase is essential for coupling inflammatory cytokine signals to the
      cell death machinery in the differentiated mammary epithelium.

PMID- 27044868
TI  - Mechanism of Lysine 48 Selectivity during Polyubiquitin Chain Formation by the
      Ube2R1/2 Ubiquitin-Conjugating Enzyme.
AB  - Lysine selectivity is of critical importance during polyubiquitin chain formation
      because the identity of the lysine controls the biological outcome. Ubiquitins
      are covalently linked in polyubiquitin chains through one of seven lysine
      residues on its surface and the C terminus of adjacent protomers. Lys 48-linked
      polyubiquitin chains signal for protein degradation; however, the structural
      basis for Lys 48 selectivity remains largely unknown. The ubiquitin-conjugating
      enzyme Ube2R1/2 has exquisite specificity for Lys 48, and computational docking
      of Ube2R1/2 and ubiquitin predicts that Lys 48 is guided to the active site
      through a key electrostatic interaction between Arg 54 on ubiquitin and Asp 143
      on Ube2R1/2. The validity of this interaction was confirmed through biochemical
      experiments. Since structural examples involving Arg 54 in protein-ubiquitin
      complexes are exceedingly rare, these results provide additional insight into how
      ubiquitin-protein complexes can be stabilized. We discuss how these findings
      relate to how other ubiquitin-conjugating enzymes direct the lysine specificity
      of polyubiquitin chains.

PMID- 27044869
TI  - Endogenous Hot Spots of De Novo Telomere Addition in the Yeast Genome Contain
      Proximal Enhancers That Bind Cdc13.
AB  - DNA double-strand breaks (DSBs) pose a threat to genome stability and are
      repaired through multiple mechanisms. Rarely, telomerase, the enzyme that
      maintains telomeres, acts upon a DSB in a mutagenic process termed telomere
      healing. The probability of telomere addition is increased at specific genomic
      sequences termed sites of repair-associated telomere addition (SiRTAs). By
      monitoring repair of an induced DSB, we show that SiRTAs on chromosomes V and IX
      share a bipartite structure in which a core sequence (Core) is directly targeted
      by telomerase, while a proximal sequence (Stim) enhances the probability of de
      novo telomere formation. The Stim and Core sequences are sufficient to confer a
      high frequency of telomere addition to an ectopic site. Cdc13, a single-stranded
      DNA binding protein that recruits telomerase to endogenous telomeres, is known to
      stimulate de novo telomere addition when artificially recruited to an induced
      DSB. Here we show that the ability of the Stim sequence to enhance de novo
      telomere addition correlates with its ability to bind Cdc13, indicating that
      natural sites at which telomere addition occurs at high frequency require binding
      by Cdc13 to a sequence 20 to 100 bp internal from the site at which telomerase
      acts to initiate de novo telomere addition.

PMID- 27044870
TI  - Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical
      for Lymphatic Vascular Development and Function.
AB  - The molecular mechanisms underlying lymphatic vascular development and function
      are not well understood. Recent studies have suggested a role for endothelial
      cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in
      developmental angiogenesis and atherosclerosis. Here, we show that constitutive
      loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax,
      suggesting that Map4k4 is required for normal lymphatic vascular function. Mice
      constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries,
      insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary
      ECs derived from these animals displayed enhanced proliferation compared with
      controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein
      Rasa1, a known regulator of lymphatic development and lymphatic endothelial cell
      fate, as a direct interacting partner for Map4k4. Map4k4 silencing in ECs
      enhanced basal Ras and extracellular signal-regulated kinase (Erk) activities,
      and primary ECs lacking Map4k4 displayed enhanced lymphatic EC marker expression.
      Taken together, these results reveal that EC Map4k4 is critical for lymphatic
      vascular development by regulating EC quiescence and lymphatic EC fate.

PMID- 27044872
TI  - Patients as story-tellers of healthcare journeys.
AB  - There are gaps in our comprehension of patients' subjective experiences as they
      engage with and transit through the healthcare environments implicated in their
      treatment trajectories. Patients' stories, unlike patient experience data
      gathered in questionnaires and surveys, express the deeply personal, narrative
      nature of the journeys that patients take, creating opportunities for qualitative
      healthcare research. Yet narrative capabilities and propensities vary with
      individuals, and are affected by the stresses of illness and treatment. This
      article extends the growing interest in narrative competence training for both
      practitioners and patients with the investigation of a story-telling model that
      could facilitate patients to narrate their experiences of healthcare systems.
      This model is derived from the literary arts. In fiction and autobiography, the
      journey arc of the central character is often one in which he or she is compelled
      to leave the comfort of everyday life and face a series of extraordinary events
      involving challenge and change which forces the character towards practical,
      intellectual, psychological and philosophical adjustments that define, by the end
      of the story, the character's 'new normal'. This pattern is known as the 'hero
      journey'. Its parallels with patients' experiences of healthcare and the way
      people narrate their stories of illness have long been recognised. We present
      here a new idea for applying this model as a narrative structure by which
      patients may construct their stories about being in and moving through the
      healthcare system. 

PMID- 27044871
TI  - Intact Cell MALDI-TOF MS on Sperm: A Molecular Test For Male Fertility Diagnosis.
AB  - Currently, evaluation of sperm quality is primarily based on in vitro measures of
      sperm function such as motility, viability and/or acrosome reaction. However,
      results are often poorly correlated with fertility, and alternative diagnostic
      tools are therefore needed both in veterinary and human medicine. In a recent
      pilot study, we demonstrated that MS profiles from intact chicken sperm using
      MALDI-TOF profiles could detect significant differences between
      fertile/subfertile spermatozoa showing that such profiles could be useful for in
      vitro male fertility testing. In the present study, we performed larger
      standardized experimental procedures designed for the development of fertility-
      predictive mathematical models based on sperm cell MALDI-TOF MS profiles acquired
      through a fast, automated method. This intact cell MALDI-TOF MS-based method
      showed high diagnostic accuracy in identifying fertile/subfertile males in a
      large male population of known fertility from two distinct genetic lineages (meat
      and egg laying lines). We additionally identified 40% of the m/z peaks observed
      in sperm MS profiles through a top-down high-resolution protein identification
      analysis. This revealed that the MALDI-TOF MS spectra obtained from intact sperm
      cells contained a large proportion of protein degradation products, many
      implicated in important functional pathways in sperm such as energy metabolism,
      structure and movement. Proteins identified by our predictive model included
      diverse and important functional classes providing new insights into sperm
      function as it relates to fertility differences in this experimental system.
      Thus, in addition to the chicken model system developed here, with the use of
      appropriate models these methods should effectively translate to other animal
      taxa where similar tests for fertility are warranted.

PMID- 27044873
TI  - The ability of White Leghorn hens with trimmed comb and wattles to
      thermoregulate.
AB  - It is estimated that each year over 19 million pullets in the United States have
      their combs partially trimmed at a young age to improve egg production and feed
      efficiency. A possible disadvantage of trimming is that the comb and wattles may
      be essential for thermoregulation during hot weather allowing for conductive
      cooling of the blood through vasodilation of superficial vessels in these
      integumentary tissues. The objective of this study was to investigate the effects
      of partial comb and wattle removal, performed at 21 d of age, on the ability of
      White Leghorns to thermoregulate before, during, and after an imposed heating
      episode that averaged 34.6 degrees C for 50.5 h. An increase in mortality at 20 h
      and body temperature at 48 h post initiation of the heating episode demonstrated
      that hens with trimmed comb and wattles were not able to cope with heat stress as
      effectively as controls. The increase in wattle temperature in controls as
      compared to trimmed hens during the heating episode and following heat stress
      provides supportive evidence that blood pools to the peripheral surface for
      conductive heat loss. During high temperatures typical of summer, trimmed hens
      attempted to compensate for their lack of ability to transfer heat from their
      comb and wattles to the environment through increased proportion of panting and
      wing spreading. Under less extreme conditions with lowered ambient temperatures,
      the trimming of the comb and wattles did not impair the ability of hens to
      thermoregulate, as body temperatures and behavior were similar to controls with
      no mortality. Egg weight was the only production parameter adversely affected by
      the trimming of the comb and wattles as compared to controls. The implication is
      that hens need their combs and wattles to thermoregulate effectively during
      periods of high environmental temperature. Pullets should not be subjected to a
      comb and wattle trim if they are housed in laying facilities that are not
      appropriately cooled during the summer. 

PMID- 27044874
TI  - Effect of tea polyphenols on production performance, egg quality, and hepatic
      antioxidant status of laying hens in vanadium-containing diets.
AB  - This study was conducted to determine the effect of tea polyphenols (TP) on
      production performance, egg quality, and hepatic-antioxidant status of laying
      hens in vanadium-containing diets. A total of 300 Lohman laying hens (67 wk old)
      were used in a 1 plus 3 * 3 experiment design in which hens were given either a
      diet without vanadium and TP supplementation (control) or diets supplemented with
      5, 10, or 15 mg V/kg and TP (0, 600, 1,000 mg/kg) diets for 8 wk, which included
      2 phases: a 5-wk accumulation phase and a 3-wk depletion phase. During the
      accumulation phase, dietary vanadium addition decreased (linear, P < 0.01)
      albumen height and Haugh unit (HU), and TP supplementation mitigated (linear
      effect, P < 0.01) this reduction effect induced by vanadium. Eggshell thickness
      (linear, P < 0.01), redness (linear and quadratic, P < 0.05), and yellowness
      (linear and quadratic, P < 0.05) were decreased by vanadium and increased by the
      effect of TP when a vanadium-containing diet was fed. In the depletion phase, the
      bleaching effect on eggshells induced by vanadium disappeared one wk after
      vanadium withdrawal. Eggshell thickness, eggshell strength, albumen height, and
      HU were lower (P < 0.05) in the 15 mg/kg vanadium group compared with the control
      diet until 2 wk post vanadium challenge, but hens fed 15 mg/kg vanadium and 600
      mg/kg TP showed no difference from the control diet only after 1 wk withdrawal.
      In the liver, the activity of glutathione S-transferases and glutathione
      peroxidase was increased (linear, P < 0.01) with the TP addition at 5 wk in the
      accumulation phase in the vanadium-containing diet; the malondialdehyde content
      increased (linear effect, P = 0.02) with the addition of vanadium. The results
      indicate that supplementation of 10 and 15 mg/kg vanadium resulted in reduced
      albumen quality, bleaching effect on eggshell color, and antioxidant stress in
      the liver. The effect of TP addition can prevent laying hens from the adverse
      effect of vanadium on egg quality, liver antioxidant stress and shorten the
      recovery time. 

PMID- 27044875
TI  - Dust-bathing behavior of laying hens in enriched colony housing systems and an
      aviary system.
AB  - The dust-bathing behavior of Lohmann Selected Leghorn hens was compared in 4
      enriched colony housing systems and in an aviary system. The enriched colony
      housing systems differed especially in the alignment and division of the
      functional areas dust bath, nest, and perches. Forty-eight-hour video recordings
      were performed at 3 time-points during the laying period, and focal animal
      sampling and behavior sampling methods were used to analyze the dust-bathing
      behavior. Focal animal data included the relative fractions of dust-bathing hens
      overall, of hens bathing in the dust-bath area, and of those bathing on the wire
      floor throughout the day. Behavior data included the number of dust-bathing bouts
      within a predefined time range, the duration of 1 bout, the number of and reasons
      for interruptions, and the number of and reasons for the termination of dust
      bathing bouts. Results showed that the average duration of dust bathing varied
      between the 4 enriched colony housing systems compared with the aviary system.
      The duration of dust-bathing bouts was shorter than reported under natural
      conditions. A positive correlation between dust-bathing activity and size of the
      dust-bath area was observed. Frequently, dust baths were interrupted and
      terminated by disturbing influences such as pecking by other hens. This was
      especially observed in the enriched colony housing systems. In none of the
      observed systems, neither in the enriched colony housing nor in the aviary
      system, were all of the observed dust baths terminated "normally." Dust bathing
      behavior on the wire mesh rather than in the provided dust-bath area generally
      was observed at different frequencies in all enriched colony housing systems
      during all observation periods, but never in the aviary system. The size and
      design of the dust-bath area influenced the prevalence of dust-bathing behavior
      in that small and subdivided dust-bath areas reduced the number of dust-bathing
      bouts but increased the incidence of sham dust bathing on the wire mesh. 

PMID- 27044876
TI  - Multimotor Driven Cargos: From Single Motor under Load to the Role of Motor-Motor
      Coupling.
AB  - Motor proteins constitute an essential part of the cellular machinery. They have
      been the subject of intensive studies in the past two decades. Yet, when several
      motors simultaneously carry a single cargo, the effect of motor-motor coupling,
      such as mutual stalling and jamming, remains unclear. We commence by constructing
      a general model for single motor motion, which is a product of a derived load
      dependent expression and a phenomenological motor specific function. Forming the
      latter according to recent single molecule measurements for a given load, the
      model correctly predicts the motor full step-size distribution for all other
      measured loads. We then use our proposed model to predict transport properties of
      multimotor complexes, with particular attention to 1-dimensional constructs with
      variable flexibility, motor density, and number of motors: (i) a chain of motors
      connected by springs, a recently studied construction of a pair, and (ii) an
      array of motors all connected by identical springs to a stiff rod, which is
      essentially a mirror image of standard gliding motility assays. In both systems,
      and for any number of carrying motors, we find that, while low flexibility
      results in a strongly damped velocity, increased flexibility renders an almost
      single motor velocity. Comparing our model based simulations to recent gliding
      assays we find remarkable qualitative agreement. We also demonstrate consistency
      with other multimotor motility assays. In all cases, the characteristic spring
      constant, that controls the crossover behavior between high and low velocity
      regimes, is found to be the stalling force divided by the mean step size. We
      conjecture that this characteristic spring constant can serve as a tool for
      engineering multimotor complexes.

PMID- 27044877
TI  - Surgical exploration of the submerged part of the iceberg.

PMID- 27044878
TI  - Selection of individuals for genetic testing for familial hypercholesterolaemia:
      development and external validation of a prediction model for the presence of a
      mutation causing familial hypercholesterolaemia.
AB  - Aims: Familial hypercholesterolaemia (FH) is an autosomal dominant disease that
      warrants early diagnosis to prevent premature cardiovascular disease (CVD).
      However, genetic testing to make a definite diagnosis is costly, and careful
      selection of eligible subjects is important. Unfortunately, accuracy of current
      diagnostic criteria is poor, especially in young individuals. We therefore
      developed and validated a model to predict the presence of an FH causing mutation
      in persons referred by general practitioners. Methods and results: All
      participants in the Dutch FH screening programme from 1994 to 2014 were included
      in the development cohort. The validation cohort consisted of consecutive
      patients, suspected for FH, attending the outpatient lipid clinic in Saguenay
      (Quebec) from 1993 to 2014. Cross-sectional data were available on medical
      history, lipid profile, and DNA analysis. Multivariable logistic regression
      analysis was used for model development. The primary outcome was the presence of
      a deleterious FH mutation. The development cohort comprised 26 167 FH patients
      and 37 939 unaffected relatives. Our final model included age; sex; levels of low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol,
      and triglycerides; history and age of CVD; use of statins; smoking; alcohol; and
      presence of hypertension. The area under the receiver operating characteristic
      curve (AUC) was 85.4% (95% CI: 85.0-85.9). The calibration slope was 1.02 (where
      1.00 is optimal). In the validation cohort (1436 FH patients and 1767 unaffected
      persons), the AUC was 95.4% (95% CI: 94.7-96.1%) and the calibration slope 1.06.
      Conclusion: Our model showed good discrimination and calibration. We specifically
      expect our model to be of added value for young persons set against current
      diagnostic criteria, since LDL-C and age are now used as continuous predictors.
      The equation will be available as an online calculator to estimate the
      probability of the presence of an FH mutation in individual patients. This tool
      might aid physicians in the decision for referral of patients for molecular
      testing.

PMID- 27044879
TI  - A late acquired 'black hole' after ablation-induced damage to the circumflex
      artery.

PMID- 27044880
TI  - The venous U-turn: a unique variant of total anomalous superior systemic venous
      return.

PMID- 27044881
TI  - Improving feedback on junior doctors' prescribing errors: mixed-methods
      evaluation of a quality improvement project.
AB  - BACKGROUND: Prescribing errors occur in up to 15% of UK inpatient medication
      orders. However, junior doctors report insufficient feedback on errors. A barrier
      preventing feedback is that individual prescribers often cannot be clearly
      identified on prescribing documentation. AIM: To reduce prescribing errors in a
      UK hospital by improving feedback on prescribing errors. INTERVENTIONS: We
      developed three linked interventions using plan-do-study-act cycles: (1) name
      stamps for junior doctors who were encouraged to stamp or write their name
      clearly when prescribing; (2) principles of effective feedback to support
      pharmacists to provide feedback to doctors on individual prescribing errors and
      (3) fortnightly prescribing advice emails that addressed a common and/or serious
      error. IMPLEMENTATION AND EVALUATION: Interventions were introduced at one
      hospital site in August 2013 with a second acting as control. Process measures
      included the percentage of inpatient medication orders for which junior doctors
      stated their name. Outcome measures were junior doctors' and pharmacists'
      perceptions of current feedback provision (evaluated using quantitative pre
      questionnaires and post-questionnaires and qualitative focus groups) and the
      prevalence of erroneous medication orders written by junior doctors between
      August and December 2013. RESULTS: The percentage of medication orders for which
      junior doctors stated their name increased from about 10% to 50%. Questionnaire
      responses revealed a significant improvement in pharmacists' perceptions but no
      significant change for doctors. Focus group findings suggested increased doctor
      engagement with safe prescribing. Interrupted time series analysis showed no
      difference in weekly prescribing error rates between baseline and intervention
      periods, compared with the control site. CONCLUSION: Findings suggest improved
      experiences around feedback. However, attempts to produce a measurable reduction
      in prescribing errors are likely to need a multifaceted approach of which
      feedback should form part.

PMID- 27044882
TI  - Association of IGF1 and IGF1R gene polymorphisms with high myopia in a Han
      Chinese population.
AB  - OBJECTIVES: Insulin-like growth factor 1 (IGF1) and insulin-like growth factor 1
      receptor (IGF1R) have been shown to influence the development of form-deprivation
      myopia. However, genetic association between these two genes and high myopia
      remains inconsistent in different studies. This study was conducted to
      investigate the association between IGF1and IGF1R and high myopia in a Han
      Chinese population. METHODS: Fourteen single nucleotide polymorphisms (SNPs) in
      the IGF1 and IGF1R genes were genotyped by SNaPshot method in a Han Chinese
      subject group composed of 1244 high myopia patients and 1380 controls. The
      genotyping data was analyzed by chi2 test and the linkage disequilibrium block
      structure was examined by Haploview software. RESULTS: There were no
      statistically significant differences in the allele frequencies of IGF1 and IGF1R
      SNPs and genotypes between patients and controls after Bonferroni multiple
      correction (p > 0.05). However, the G allele of rs35766 in the IGF1 gene showed a
      protective effect for high myopia (p = 0.015, corrected p = 0.21, odds ratio [OR]
      = 0.77, 95% CI = 0.70-0.97). The carriers of rs35766GG and rs35766GG+AG genotypes
      displayed a decreased risk of high myopia compared with rs35766AA carriers (p =
      0.012, OR = 0.65, 95% CI = 0.47-0.91; p = 0.019, OR = 0.68, 95% CI = 0.50-0.94,
      respectively). CONCLUSIONS: Genetic variants in the IGF1 and IGF1R genes might
      not be associated with high myopia in Han Chinese. Further studies are needed to
      verify the possible function of IGF1 and IGF1R in the development of myopia.

PMID- 27044883
TI  - Effects of Design Features of Explicit Values Clarification Methods: A Systematic
      Review.
AB  - BACKGROUND: Diverse values clarification methods exist. It is important to
      understand which, if any, of their design features help people clarify values
      relevant to a health decision. PURPOSE: To explore the effects of design features
      of explicit values clarification methods on outcomes including decisional
      conflict, values congruence, and decisional regret. DATA SOURCES: MEDLINE, all
      EBM Reviews, CINAHL, EMBASE, Google Scholar, manual search of reference lists,
      and expert contacts. STUDY SELECTION: Articles were included if they described
      the evaluation of 1 or more explicit values clarification methods. DATA
      EXTRACTION: We extracted details about the evaluation, whether it was conducted
      in the context of actual or hypothetical decisions, and the results of the
      evaluation. We combined these data with data from a previous review about each
      values clarification method's design features. DATA SYNTHESIS: We identified 20
      evaluations of values clarification methods within 19 articles. Reported outcomes
      were heterogeneous. Few studies reported values congruence or postdecision
      outcomes. The most promising design feature identified was explicitly showing
      people the implications of their values, for example, by displaying the extent to
      which each of their decision options aligns with what matters to them.
      LIMITATIONS: Because of the heterogeneity of outcomes, we were unable to perform
      a meta-analysis. Results should be interpreted with caution. CONCLUSIONS: Few
      values clarification methods have been evaluated experimentally. More research is
      needed to determine effects of different design features of values clarification
      methods and to establish best practices in values clarification. When feasible,
      evaluations should assess values congruence and postdecision measures of longer
      term outcomes.

PMID- 27044884
TI  - Linear extrapolation of missing radiographic change scores in clinical trials
      does not spuriously overestimate group radiographic changes in rheumatoid
      arthritis.
AB  - OBJECTIVE: To assess linear extrapolation (LE) and last observation carried
      forward (LOCF) as imputation methods for radiographic change in patients with RA.
      METHODS: The OSKIRA-1 trial enrolled 918 patients with active RA for studying the
      efficacy of fostamatinib. Radiographs were scheduled for all patients at baseline
      and week 12, regardless of early escape, and at weeks 24 and 52 for patients who
      remained in the study. Complete radiographic data for the 24-week follow-up were
      available for 623 patients and were assessed according to the Sharp/van der
      Heijde score. From this complete set of data, a random selection of 10%
      missingness was generated. This was done 1000 times, and for each replicate the
      missing radiographic change at week 24 was imputed, first by LE, then by LOCF.
      The mean of the mean and mean of the s.d. across the 1000 replications was
      calculated. A similar approach was iterated for different proportions of
      missingness. RESULTS: The mean (s.d.) observed Sharp/van der Heijde score change
      from baseline to week 24 was 0.36 (2.39). With LE, the mean (s.d.) change was
      estimated as 0.36 (2.65), 0.35 (2.88), 0.35 (3.17), 0.34 (3.57) and 0.32 (4.45)
      with 10/20/30/50/90% missingness, respectively. With LOCF, the mean (s.d.) change
      was estimated as 0.34 (2.39), 0.32 (2.38), 0.30 (2.37), 0.26 (2.36) and 0.18
      (2.34) with 10/20/30/50/90% missingness, respectively. CONCLUSION: LE led to
      stable estimates of progression at the group level, but increasing variability
      with increasing proportions of missingness. In contrast, LOCF imputation
      systemically underestimated mean progression with increasing proportions of
      missingness, with artificially reduced variability estimates.

PMID- 27044885
TI  - Targeting Recovery in Persistent Persecutory Delusions: A Proof of Principle
      Study of a New Translational Psychological Treatment (the Feeling Safe
      Programme).
AB  - BACKGROUND: Many patients do not respond adequately to current pharmacological or
      psychological treatments for psychosis. Persistent persecutory delusions are
      common in clinical services, and cause considerable patient distress and
      impairment. Our aim has been to build a new translational personalized treatment,
      with the potential for wide use, that leads to high rates of recovery in
      persistent persecutory delusions. We have been developing, and evaluating
      individually, brief modular interventions, each targeting a key causal factor
      identified from our cognitive model. These modules are now combined in "The
      Feeling Safe Programme". AIMS: To test the feasibility of a new translational
      modular treatment for persistent persecutory delusions and provide initial
      efficacy data. METHOD: 12 patients with persistent persecutory delusions in the
      context of non-affective psychosis were offered the 6-month Feeling Safe
      Programme. After assessment, patients chose from a personalized menu of treatment
      options. Four weekly baseline assessments were carried out, followed by monthly
      assessments. Recovery in the delusion was defined as conviction falling below 50%
      (greater doubt than certainty). RESULTS: 11 patients completed the intervention.
      One patient withdrew before the first monthly assessment due to physical health
      problems. An average of 20 sessions (SD = 4.4) were received. Posttreatment, 7
      out of 11 (64%) patients had recovery in their persistent delusions. Satisfaction
      ratings were high. CONCLUSIONS: The Feeling Safe Programme is feasible to use and
      was associated with large clinical benefits. To our knowledge this is the first
      treatment report focused on delusion recovery. The treatment will be tested in a
      randomized controlled trial.

PMID- 27044886
TI  - Synthesis of micro-sized shell-isolated 3D plasmonic superstructures for in situ
      single-particle SERS monitoring.
AB  - A single-particle SERS system enabling real-time and in situ observation of Au
      catalyzed reactions has been developed. Both the catalytic activity and the SERS
      effect are coupled into a single bi-functional 3D superstructure comprising Au
      nanosatellites self-assembled onto a shell-insulated Ag microflower core, which
      eliminates the interference from photocatalysis. 

PMID- 27044887
TI  - Randomised intervention study to assess the prevalence of subclinical vascular
      disease and hidden kidney disease and its impact on morbidity and mortality: The
      ILERVAS project.
AB  - BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) and atherosclerosis are 2
      interrelated diseases that increase the risk of cardiovascular morbidity and
      mortality. The objectives of the ILERVAS project are: 1) to determine the
      prevalence of subclinical arterial disease and hidden kidney disease; 2) to
      assess the impact of early diagnosis of both diseases on cardiovascular morbidity
      and mortality and also on the progression of CKD; 3) to have a platform of data
      and biological samples. METHODS: Randomized intervention study. From 2015 to
      2017, 19,800 people (9,900 in the intervention group and 9,900 in the control
      group) aged between 45 and 70 years without previous history of cardiovascular
      disease and with at least one cardiovascular risk factor will be randomly
      selected from the primary health care centres across the province of Lerida. A
      team of experts will travel around in a mobile unit to carry out the following
      baseline tests on the intervention group: Artery ultrasound; (carotid, femoral,
      transcranial and abdominal aorta); ankle-brachial index; spirometry;
      determination of advanced glycation end products; dried blood spot and urine spot
      tests. Additionally, blood and urine samples will be collected and stored in the
      biobank to identify new biomarkers using omics studies. Participants will be
      followed up until 2025 for identification of cardiovascular events, treatment
      changes and changes in lifestyle. CONCLUSIONS: The ILERVAS project will reveal
      the prevalence of subclinical vascular disease and hidden kidney disease,
      determine whether or not their early diagnosis brings health benefits and will
      also allow investigation of new risk factors.

PMID- 27044888
TI  - Th17 responses and natural IgM antibodies are related to gut microbiota
      composition in systemic lupus erythematosus patients.
AB  - Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio,
      has been reported in systemic lupus erythematosus (SLE) patients. In this study,
      in vitro cultures revealed that microbiota isolated from SLE patient stool
      samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from
      naive CD4(+) lymphocytes to a greater extent than healthy control-microbiota.
      Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two
      Clostridia strains significantly reduced the Th17/Th1 balance, whereas
      Bifidobacterium bifidum supplementation prevented CD4(+) lymphocyte over
      activation, thus supporting a possible therapeutic benefit of probiotics
      containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance
      present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17
      and Foxp3(+) IL-17(+) populations, suggesting a possible Treg-Th17 trans
      differentiation. Moreover, analyses of fecal microbiota revealed a negative
      correlation between IL-17(+) populations and Firmicutes in healthy controls,
      whereas in SLE this phylum correlated directly with serum levels of IFNgamma, a
      Th1 cytokine slightly reduced in patients. Finally, the frequency of
      Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in
      healthy controls, tended to be reduced in patients when anti-dsDNA titers were
      increased and showed a strong negative correlation with IL-6 serum levels and
      correlated positively with protective natural IgM antibodies against
      phosphorylcholine. 

PMID- 27044889
TI  - Doa1 targets ubiquitinated substrates for mitochondria-associated degradation.
AB  - Mitochondria-associated degradation (MAD) mediated by the Cdc48 complex and
      proteasome degrades ubiquitinated mitochondrial outer-membrane proteins. MAD is
      critical for mitochondrial proteostasis, but it remains poorly characterized. We
      identified several mitochondrial Cdc48 substrates and developed a genetic screen
      assay to uncover regulators of the Cdc48-dependent MAD pathway. Surprisingly, we
      identified Doa1, a substrate-processing factor of Cdc48 that inhibits the
      degradation of some Cdc48 substrates, as a critical mediator of the turnover of
      mitochondrial Cdc48 substrates. Deletion ofDOA1causes the accumulation and
      mislocalization of substrates on mitochondria. Profiling of Cdc48 cofactors shows
      that Doa1 and Cdc48(-Ufd1-Npl4)form a functional complex mediating MAD.
      Biochemically, Doa1 interacts with ubiquitinated substrates and facilitates
      substrate recruitment to the Cdc48(-Ufd1-Npl4)complex. Functionally, Doa1 is
      critical for cell survival under mitochondrial oxidative stress, but not ER
      stress, conditions. Collectively, our results demonstrate the essential role of
      the Doa1-Cdc48(-Ufd1-Npl4)complex in mitochondrial proteostasis and suggest that
      Doa1 plays dual roles on the Cdc48 complex. 

PMID- 27044890
TI  - Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate
      phosphoinositides.
AB  - Endoplasmic reticulum-plasma membrane (ER-PM) contact sites play an integral role
      in cellular processes such as excitation-contraction coupling and store-operated
      calcium entry (SOCE). Another ER-PM assembly is one tethered by the extended
      synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions
      the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER-PM
      junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM
      phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P2 Activation
      of G protein-coupled receptors that deplete PM PI(4,5)P2disrupts E-Syt2-mediated
      ER-PM junctions, reducing Sac1's access to the PM and permitting PM PI(4)P and
      PI(4,5)P2to recover. Conversely, depletion of ER luminal calcium and subsequent
      activation of SOCE increases the amount of Sac1 in contact with the PM, depleting
      PM PI(4)P. Thus, the dynamic presence of Sac1 at ER-PM contact sites allows it to
      act as a cellular sensor and controller of PM phosphoinositides, thereby
      influencing many PM processes. 

PMID- 27044891
TI  - P53- and mevalonate pathway-driven malignancies require Arf6 for metastasis and
      drug resistance.
AB  - Drug resistance, metastasis, and a mesenchymal transcriptional program are
      central features of aggressive breast tumors. The GTPase Arf6, often
      overexpressed in tumors, is critical to promote epithelial-mesenchymal transition
      and invasiveness. The metabolic mevalonate pathway (MVP) is associated with tumor
      invasiveness and known to prenylate proteins, but which prenylated proteins are
      critical for MVP-driven cancers is unknown. We show here that MVP requires the
      Arf6-dependent mesenchymal program. The MVP enzyme geranylgeranyl transferase II
      (GGT-II) and its substrate Rab11b are critical for Arf6 trafficking to the plasma
      membrane, where it is activated by receptor tyrosine kinases. Consistently,
      mutant p53, which is known to support tumorigenesis via MVP, promotes Arf6
      activation via GGT-II and Rab11b. Inhibition of MVP and GGT-II blocked invasion
      and metastasis and reduced cancer cell resistance against chemotherapy agents,
      but only in cells overexpressing Arf6 and components of the mesenchymal program.
      Overexpression of Arf6 and mesenchymal proteins as well as enhanced MVP activity
      correlated with poor patient survival. These results provide insights into the
      molecular basis of MVP-driven malignancy. 

PMID- 27044892
TI  - Kindlin-2 directly binds actin and regulates integrin outside-in signaling.
AB  - Reduced levels of kindlin-2 (K2) in endothelial cells derived from K2(+/-)mice or
      C2C12 myoblastoid cells treated with K2 siRNA showed disorganization of their
      actin cytoskeleton and decreased spreading. These marked changes led us to
      examine direct binding between K2 and actin. Purified K2 interacts with F-actin
      in cosedimentation and surface plasmon resonance analyses and induces actin
      aggregation. We further find that the F0 domain of K2 binds actin. A mutation,
      LK(47)/AA, within a predicted actin binding site (ABS) of F0 diminishes its
      interaction with actin by approximately fivefold. Wild-type K2 and K2 bearing the
      LK(47)/AA mutation were equivalent in their ability to coactivate integrin
      alphaIIbbeta3 in a CHO cell system when coexpressed with talin. However, K2
      LK(47)/AA exhibited a diminished ability to support cell spreading and actin
      organization compared with wild-type K2. The presence of an ABS in F0 of K2 that
      influences outside-in signaling across integrins establishes a new foundation for
      considering how kindlins might regulate cellular responses. 

PMID- 27044893
TI  - Septins recognize micron-scale membrane curvature.
AB  - How cells recognize membrane curvature is not fully understood. In this issue,
      Bridges et al. (2016.J. Cell Biol.http://dx.doi.org/10.1083/jcb.201512029)
      discover that septins, a component of the cytoskeleton, recognize membrane
      curvature at the micron scale, a common morphological hallmark of eukaryotic
      cellular processes. 

PMID- 27044894
TI  - Doa1 is a MAD adaptor for Cdc48.
AB  - Dislocation of polypeptides from the mitochondrial outer membrane by the
      p97/Cdc48-Ufd1-Npl4 adenosine triphosphatase complex is essential for
      mitochondria-associated degradation and Parkin-mediated mitophagy. In this issue,
      Wu et al. (2016.J. Cell Biol.http://dx.doi.org/10.1083/jcb.201510098) identify
      Doa1 as a pivotal adaptor that recruits substrates to Cdc48 for processing.

PMID- 27044895
TI  - Rapid and dynamic transcriptome regulation by RNA editing and RNA modifications.
AB  - Advances in next-generation sequencing and mass spectrometry have revealed
      widespread messenger RNA modifications and RNA editing, with dramatic effects on
      mammalian transcriptomes. Factors introducing, deleting, or interpreting specific
      modifications have been identified, and analogous with epigenetic terminology,
      have been designated "writers," "erasers," and "readers." Such modifications in
      the transcriptome are referred to as epitranscriptomic changes and represent a
      fascinating new layer of gene expression regulation that has only recently been
      appreciated. Here, we outline how RNA editing and RNA modification can rapidly
      affect gene expression, making both processes as well suited to respond to
      cellular stress and to regulate the transcriptome during development or circadian
      periods. 

PMID- 27044896
TI  - Micron-scale plasma membrane curvature is recognized by the septin cytoskeleton.
AB  - Cells change shape in response to diverse environmental and developmental
      conditions, creating topologies with micron-scale features. Although individual
      proteins can sense nanometer-scale membrane curvature, it is unclear if a cell
      could also use nanometer-scale components to sense micron-scale contours, such as
      the cytokinetic furrow and base of neuronal branches. Septins are filament
      forming proteins that serve as signaling platforms and are frequently associated
      with areas of the plasma membrane where there is micron-scale curvature,
      including the cytokinetic furrow and the base of cell protrusions. We report here
      that fungal and human septins are able to distinguish between different degrees
      of micron-scale curvature in cells. By preparing supported lipid bilayers on
      beads of different curvature, we reconstitute and measure the intrinsic septin
      curvature preference. We conclude that micron-scale curvature recognition is a
      fundamental property of the septin cytoskeleton that provides the cell with a
      mechanism to know its local shape. 

PMID- 27044897
TI  - A versatile multivariate image analysis pipeline reveals features of Xenopus
      extract spindles.
AB  - Imaging datasets are rich in quantitative information. However, few cell
      biologists possess the tools necessary to analyze them. Here, we present a large
      dataset of Xenopusextract spindle images together with an analysis pipeline
      designed to assess spindle morphology across a range of experimental conditions.
      Our analysis of different spindle types illustrates how kinetochore microtubules
      amplify spindle microtubule density. Extract mixing experiments reveal that some
      spindle features titrate, while others undergo switch-like transitions, and
      multivariate analysis shows the pleiotropic morphological effects of modulating
      the levels of TPX2, a key spindle assembly factor. We also apply our pipeline to
      analyze nuclear morphology in human cell culture, showing the general utility of
      the segmentation approach. Our analyses provide new insight into the diversity of
      spindle types and suggest areas for future study. The approaches outlined can be
      applied by other researchers studying spindle morphology and adapted with minimal
      modification to other experimental systems.

PMID- 27044898
TI  - Yoga and physical exercise - a review and comparison.
AB  - Yoga is a multifaceted spiritual tool with enhanced health and well-being as one
      of its positive effects. The components of yoga which are very commonly applied
      for health benefits are asanas (physical postures), pranayama (regulated
      breathing) and meditation. In the context of asanas, yoga resembles more of a
      physical exercise, which may lead to the perception that yoga is another kind of
      physical exercise. This article aims at exploring the commonalities and
      differences between yoga and physical exercise in terms of concepts, possible
      mechanisms and effectiveness for health benefits. A narrative review is
      undertaken based on traditional and contemporary literature for yoga, along with
      scientific articles available on yoga and exercise including head-to-head
      comparative trials with healthy volunteers and patients with various disease
      conditions. Physical exercises and the physical components of yoga practices have
      several similarities, but also important differences. Evidence suggests that yoga
      interventions appear to be equal and/or superior to exercise in most outcome
      measures. Emphasis on breath regulation, mindfulness during practice, and
      importance given to maintenance of postures are some of the elements which
      differentiate yoga practices from physical exercises.

PMID- 27044899
TI  - Standardization of reporting would help to define best treatment for pulmonary
      atresia, ventricular septal defect and major aortopulmonary collateral arteries.

PMID- 27044900
TI  - Surgical outcomes for acute type A aortic dissection with aggressive primary
      entry resection.
AB  - OBJECTIVES: An entry located at aortic arch in acute type A aortic dissection
      (AAAD) is uncommon. It remains controversial whether or not aggressive primary
      entry resection should be routinely performed in such patients. We have adopted
      an aggressive strategy of entry site resection, including total arch replacement
      (TAR) in patients with arch tears. The purpose of this study was to investigate
      the efficacy of our surgical management approach, using aggressive primary entry
      resection. METHODS: Between January 2000 and December 2014, we retrospectively
      reviewed the records of 334 patients with AAAD who underwent emergent surgery.
      The mean age was 67 +/- 13 years (range, 20-95 years). Ninety-five patients (28%)
      presented with shock vital status, and 84 patients (25%) manifested malperfusion
      of branched arteries. Primary entry resection was achieved in 95% of patients
      under an aggressive surgical strategy [hemiarch replacement for 173 (52%)
      patients and TAR for 161 (48%) patients] concomitant with 22 coronary artery
      bypass grafts and 38 root replacements. Ninety-six percent of hospital survivors
      (298/311) were followed for a median of 39 months (range, 0-179 months). RESULTS:
      Operation, cardiopulmonary bypass, cardiac arrest, antegrade cerebral perfusion
      and lower body circulatory arrest times were 447 +/- 170, 236 +/- 93, 112 +/- 74,
      115 +/- 81 and 54 +/- 18 min, respectively. The 30-day mortality rate was 5.4%.
      The in-hospital mortality rate was 8.4% (6.9% at our hospital). Incidences of
      postoperative permanent neurological dysfunction, tracheotomy and newly permanent
      haemodialysis were 6.9, 8 and 2%, respectively, with no spinal cord injuries
      observed. Complete false lumen thrombosis was achieved in 57% of patients as
      visualized by postoperative computed tomography angiography. After 3, 5 and 10
      years, overall survival rates were 81, 74 and 65%, respectively, and the
      percentages of patients free from downstream dissection-related reoperation were
      89, 86 and 80%, respectively. Multivariable analysis demonstrated that the risk
      factors for downstream aortic reoperation were patent false lumen, residual
      primary entry tear and connective tissue disorder. CONCLUSIONS: The surgical
      outcomes following aggressive treatment of AAAD are satisfactory. False lumen
      thrombosis can be achieved in a relatively high proportion of patients using this
      technique, resulting in a low rate of subsequent downstream aortic reoperations.

PMID- 27044901
TI  - Considerations about the ability of computed tomography to predict the clinical
      stage of thymoma.

PMID- 27044902
TI  - Should surgeons have mental skills training?

PMID- 27044903
TI  - PET-CT in the UK: current status and future directions.
AB  - Combined positron-emission tomography and computed tomography (PET-CT) has taken
      the oncological world by storm since being introduced into the clinical domain in
      the early 21(st) century and is firmly established in the management pathway of
      many different tumour types. Non-oncological applications of PET-CT represent a
      smaller but steadily growing area of interest. PET-CT continues to be the focus
      of a large number of research studies and keeping up-to-date with the literature
      is important but represents a challenge. Consequently guidelines recommending PET
      CT usage need to be revised regularly to encompass new developments. The purpose
      of this article is twofold: first, it provides a detailed review of the evidence
      base underpinning the major uses of PET-CT in clinical practice, which may be of
      value to a wide-range of individuals, including those directly involved with PET
      CT and to a much larger group with limited exposure, but for whom a precis of the
      current state-of-play may help inform other radiology and multidisciplinary team
      (MDT) work; the second purpose is as a companion to revised guidelines on
      evidence-based indications for PET-CT in the UK (being published concurrently)
      providing a detailed commentary on new indications with a summary of emerging
      data supporting these additional clinical uses of the technique. 

PMID- 27044904
TI  - Active site characterization and structure based 3D-QSAR studies on non-redox
      type 5-lipoxygenase inhibitors.
AB  - Structure-based 3D-QSAR study was performed on a class of 5-benzylidene-2
      phenylthiazolinones non-redox type 5-LOX inhibitors. In this study, binding
      pocket of 5-Lipoxygenase (pdb id 3o8y) was identified by manual docking using 15
      LOX (pdb id 2p0m) as a reference structure. Additionally, most of the binding
      site residues were found conserved in both structures. These non-redox inhibitors
      were then docked into the binding site of 5-LOX. To generate reliable CoMFA and
      CoMSIA models, atom fit data base alignment method using docked conformation of
      the most active compound was employed. The q(2)cv and r(2)ncv values for CoMFA
      model were found to be 0.549 and 0.702, respectively. The q(2)cv and r(2)ncv
      values for the selected CoMSIA model comprised four descriptors steric,
      electrostatic, hydrophobic and hydrogen bond donor fields were found to be 0.535
      and 0.951, respectively. Obtained results showed that our generated model was
      statistically reliable. Furthermore, an external test set validates the
      reliability of the predicted model by calculating r(2)pred i.e.0.787 and 0.571
      for CoMFA and CoMSIA model, respectively. 3D contour maps generated from CoMFA
      and CoMSIA models were utilized to determine the key structural features of
      ligands responsible for biological activities. The applied protocol will be
      helpful to design more potent and selective inhibitors of 5-LOX. 

PMID- 27044905
TI  - Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation
      Patients Despite Both Standard and Aggressive Supplementation.
AB  - We recently reported that more than 70% of pediatric and young adult patients had
      a vitamin D (VD) deficiency at the time of their hematopoietic stem cell
      transplantation (HSCT). Moreover, VD deficiency was associated with inferior
      survival at 100 days after transplantation. The goal of the present study was to
      evaluate the VD requirements needed to maintain an optimal VD level (30 to 60
      ng/mL) during the first 3 months after transplantation using real-time VD
      monitoring and personalized VD supplementation. We examined 2 cohorts in this
      study: cohort 1, the "preintervention" cohort (n = 35), who were treated
      according to National Kidney Foundation guidelines for VD therapy, and cohort 2,
      the "intervention" cohort (n = 25) who were treated with high-dose VD with an
      aggressive dosage increase in those who remained VD-insufficient. Results from
      cohort 1 showed that despite aggressive monitoring and VD supplementation,
      therapeutic vitamin D levels were difficult to achieve and maintain in HSCT
      recipients during the early post-transplantation period. Only 43% of cohort 1
      achieved a therapeutic VD level, leading to our intervention in cohort 2.
      Outcomes improved in cohort 2, but still only 64% of cohort 2 patients achieved a
      therapeutic VD level despite receiving >200 IU/kg/day of VD enterally. The median
      VD level in patients who did achieve sufficient levels was 40 ng/mL, with only 1
      patient in each cohort achieving a supratherapeutic but nontoxic level. These
      data indicate that standard guidelines for VD replacement are inadequate in HSCT
      recipients, and further work is needed to define more appropriate dosing in this
      clinical setting.

PMID- 27044906
TI  - Pretransplant beta2-Microglobulin Is Associated with the Risk of Acute Graft
      versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.
AB  - The risk of acute graft-versus-host disease (aGVHD) can be reliably estimated by
      the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which
      can be further refined by the incorporation of pre-hematopoietic cell
      transplantation (HCT) serum levels of inflammatory biomarkers such as ferritin
      and albumin. beta2-Microglobulin (beta2-m) is a key component of the MHC class I
      complex, which is independently associated with mortality and frailty in the
      general population. We took advantage of our institutional protocol that includes
      measurement of pre-HCT beta2-m serum levels in the most patients to investigate
      whether pre-transplant beta2-m levels were associated with the risk of aGVHD. One
      hundred three consecutive patients submitted to allogeneic HCT, of which 26
      developed grades II to IV aGVHD, were included in the analysis. beta2-m was
      significantly associated with age and HCT-CI. Higher levels of beta2-m were
      observed in patients who developed aGVHD (P = .008). In the multivariate Cox
      regression model, beta2-m and HCT-CI remained independently associated with the
      risk of developing aGVHD. In conclusion, the association between beta2-m and the
      occurrence of aGVHD suggests that the measurement of this protein before HCT
      might represent an additional element for risk stratification of aGVHD.

PMID- 27044907
TI  - Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic
      Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.
AB  - The prognostic relevance of cytogenetics at diagnosis on the outcome of
      allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute
      lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed
      outcomes of 333 adult ALL patients who underwent alloHCT at our institution over
      a 10-year period. Patients were classified according to disease status at
      transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to
      cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or
      unknown (10%) based on available outcome data for each of the cytogenetic
      abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS),
      and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year
      nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3
      year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable
      analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for
      patients who underwent transplantation in CR1. Disease status at alloHCT was an
      independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P <
      .01) and OS (CR1 versus others: HR, 2.90; P < .01). Graft-versus-host disease
      prophylaxis with tacrolimus/sirolimus was associated with a low NRM of 11.5% in
      the alloHCT recipients in CR1. Our data indicate that cytogenetic risk is not an
      independent predictor of outcomes in alloHCT performed to treat adult ALL.

PMID- 27044908
TI  - Immobilized materials for removal of toxic metal ions from surface/groundwaters
      and aqueous waste streams.
AB  - Heavy metals from industrial processes are of special concern because they
      produce chronic poisoning in the aquatic environment. More strict environmental
      regulations on the discharge of toxic metals require the development of various
      technologies for their removal from polluted streams (i.e. industrial wastewater,
      mine waters, landfill leachate, and groundwater). The separation of toxic metal
      ions using immobilized materials (novel sorbents and membranes with doped
      ligands), due to their high selectivity and removal efficiency, increased
      stability, and low energy requirements, is promising for improving the
      environmental quality. This critical review is aimed at studying immobilized
      materials as potential remediation agents for the elimination of numerous toxic
      metal (e.g. Pb, Cd, Hg, and As) ions from polluted streams. This study covers the
      general characteristics of immobilized materials and separation processes,
      understanding of the metal ion removal mechanisms, a review of the application of
      immobilized materials for the removal of toxic metal ions, as well as the impacts
      of various parameters on the removal efficiency. In addition, emerging trends and
      opportunities in the field of remediation technologies using these materials are
      addressed. 

PMID- 27044909
TI  - Ankyrin-B in lens architecture and biomechanics: Just not tethering but more.
AB  - The ankyrins are a family of well-characterized metazoan adaptor proteins that
      play a key role in linking various membrane-spanning proteins to the underlying
      spectrin-actin cytoskeleton; a mechanistic understanding of their role in tissue
      architecture and mechanics, however, remains elusive. Here we comment on a recent
      study demonstrating a key role for ankyrin-B in maintaining the hexagonal shape
      and radial alignment of ocular lens fiber cells by regulating the membrane
      organization of periaxin, dystrophins/dystroglycan, NrCAM and spectrin-actin
      network of proteins, and revealing that ankyrin-B deficiency impairs fiber cell
      shape and mechanical properties of the ocular lens. These observations indicate
      that ankyrin-B plays an important role in maintaining tissue cytoarchitecture,
      cell shape and biomechanical properties via engaging in key protein: protein
      interactions required for membrane anchoring and organization of the spectrin
      actin skeleton, scaffolding proteins and cell adhesive proteins. 

PMID- 27044910
TI  - Free perforating branch flap for primary repairing the huge soft-tissue defects
      on the scalp and face.
AB  - OBJECTIVE: This study aimed to explore the effect of free perforating branch flap
      on the reconstruction of huge soft-tissue defects on the scalp and face. METHODS:
      Sixteen cases of huge soft-tissue defects on the scalp and face were
      reconstructed by nine latissimus dorsi-free perforator flaps and seven
      anterolateral thigh-free perforator flaps. The defects area was from 12 cm* 7 cm
      to 20 cm * 11 cm, while the flaps area was from 14 cm * 8 cm to 23 cm * 12 cm.
      The survival, planeness, chromatic aberration, radiotherapy toleration of flap
      and the function, scar of donor site were observed postoperatively. RESULT: All
      of the flaps were survived completely, and 15 cases presented for primary
      reconstruction; one underwent secondary reconstruction. One of the patients died
      one-year postoperatively due to intracranial tumor recurrence and the others had
      no recurrence. All of the flaps showed perfect shape and appropriate thickness.
      No roentgen ulcer was observed except for some extent of chromatic aberration.
      The donor-site scar was larvaceous and the function was good. CONCLUSION: This
      study indicated that the latissimus dorsi-free perforator flap or anterolateral
      thigh-free perforator flap was an ideal choice for the reconstruction of defects
      on the scalp and face.

PMID- 27044911
TI  - Effects of pH and bicarbonate on mitochondrial functions of marine bivalves.
AB  - Estuarine organisms including mollusks are exposed to periodic oxygen deficiency
      (hypoxia) that leads to a decrease in intracellular pH and accumulation of
      bicarbonate (HCO3(-)). These changes can affect cellular bioenergetics; however,
      their effects on mitochondria of estuarine mollusks are not well understood. We
      determined the interactive effects of bicarbonate (0-10mM) and pH (7.2 and 6.5)
      on mitochondrial oxygen consumption (MO2), membrane potential (Deltapsi) and
      production of reactive oxygen species (ROS) in two common estuarine bivalves -
      hard clams Mercenaria mercenaria, and bay scallops Argopecten irradians. In both
      species, elevated HCO3(-) levels suppressed ADP-stimulated (state 3) MO2 but had
      little effect on the resting (state 4) respiration. These effects were not
      mediated by the soluble adenylyl cyclase or cyclic AMP. Effects of the low pH
      (6.5) on mitochondrial traits were species-specific and depended on the substrate
      oxidized by the mitochondria. Mild acidosis (pH6.5) had minimal effects on MO2
      and Deltapsi of the bivalve mitochondria oxidizing pyruvate but led to increased
      rates of ROS production in clams (ROS production could not be measured in
      scallops). In succinate-respiring mitochondria of clams, mild acidosis suppressed
      MO2 and increased mitochondrial coupling, while in scallop mitochondria the
      effects of low pH were opposite. Suppression of mitochondrial oxidative
      phosphorylation by bicarbonate and/or acidosis may contribute to the metabolic
      rate depression during shell closure or environmental hypoxia/hypercapnia. These
      findings have implications for understanding the physiological mechanisms
      involved in regulation of mitochondrial bioenergetics during hypoxia exposure in
      estuarine bivalves.

PMID- 27044912
TI  - IgG4-related effusive constrictive pericarditis.

PMID- 27044913
TI  - Two-dimensional transthoracic echocardiographic normal reference ranges for
      proximal aorta dimensions: results from the EACVI NORRE study.
AB  - AIMS: To report normal reference ranges for echocardiographic dimensions of the
      proximal aorta obtained in a large group of healthy volunteers recruited using
      state-of-the-art cardiac ultrasound equipment, considering different measurement
      conventions, and taking into account gender, age, and body size of individuals.
      METHODS AND RESULTS: A total of 704 (mean age: 46.0 +/- 13.5 years) healthy
      volunteers (310 men and 394 women) were prospectively recruited from the
      collaborating institutions of the Normal Reference Ranges for Echocardiography
      (NORRE) study. A comprehensive echocardiographic examination was obtained in all
      subjects following pre-defined protocols. Aortic dimensions were obtained in
      systole and diastole, following both the leading-edge to leading-edge and the
      inner-edge to inner-edge conventions. Diameters were measured at four levels:
      ventricular-arterial junction, sinuses of Valsalva, sino-tubular junction, and
      proximal tubular ascending aorta. Measures of aortic root in the short-axis view
      following the orientation of each of the three sinuses were also performed. Men
      had significantly larger body sizes when compared with women, and showed larger
      aortic dimensions independently of the measurement method used. Dimensions
      indexed by height and body surface area are provided, and stratification by age
      ranges is also displayed. In multivariable analysis, the independent predictors
      of aortic dimensions were age, gender, and height or body surface area.
      CONCLUSION: The NORRE study provides normal values of proximal aorta dimensions
      as assessed by echocardiography. Reference ranges for different anatomical levels
      using different (i) measurement conventions and (ii) at different times of the
      cardiac cycle (i.e. mid-systole and end-diastole) are provided. Age, gender, and
      body size were significant determinants of aortic dimensions.

PMID- 27044914
TI  - Large intra-atrial structure 6 years after percutaneous atrial septal defect
      closure.

PMID- 27044915
TI  - Left atrial volume and strain parameters using echocardiography in a black
      population.
AB  - Aims: Left atrial (LA) volume is an important predictor of morbidity and
      mortality in cardiovascular disease. Left atrial strain is a feasible technique
      for assessing LA function. The EchoNoRMAL study recently highlighted the
      possibility that ethnic-based differences may exist in LA size. There is a
      paucity of data regarding LA parameters in an African population. We sought to
      establish normative values for LA volumetric and strain parameters in a black
      population. Methods and results: This cross-sectional study comprised 120
      individuals between 18 and 70 years of age. Left atrial volumes were measured by
      biplane Simpson's method, and strain parameters were measured using Philips QLAB
      9 (Amsterdam, The Netherlands) speckle-tracking software. The mean age was 38.7
      +/- 12.8 years (50% male). Maximum LA volume indexed (LAVi), pre-atrial LAVi, and
      minimum LAVi were 19.7 +/- 5.9, 12.2 +/- 4.4, and 7.7 +/- 3.2 mL/m2,
      respectively. Females had a higher LAVi compared with males (20.9 +/- 6.3 vs.
      18.6 +/- 5.3 mL/m2, P = 0.04). Peak global longitudinal strain in the reservoir
      phase (ER) was 39.0 +/- 8.3%, and the peak LA strain in the contractile phase
      (ECT) was -2.7 +/- 2.5%. No gender differences were noted in ER. Body surface
      area, age, and weight were the main determinants of ER on multivariate linear
      regression analysis. Conclusion: The data reported in this study establish the
      normal reference values for phasic LA volumes and strain in a normal black
      population and serve as a platform for future studies.

PMID- 27044916
TI  - Left atrial appendage closure in a patient with cor triatriatum and ASD: the
      added value of 3D echocardiography.

PMID- 27044917
TI  - Bending of the aortic valvar leaflet causing severe aortic regurgitation in a
      patient with osteogenesis imperfecta.

PMID- 27044918
TI  - Giant coronary aneurysm in a patient with non-ST myocardial infarction.

PMID- 27044919
TI  - Doppler demonstration of combined systolic pulmonary and aortic valve
      regurgitation.

PMID- 27044920
TI  - eIF4A moonlights as an off switch for TORC1.

PMID- 27044922
TI  - Pregnancy outcomes in liver transplant patients, a population-based study.
AB  - OBJECTIVE: To determine the incidence of pregnancy in liver transplant (LT)
      patients in a large population-based cohort and to determine the maternal and
      fetal risks associated with these pregnancies. METHODS: We conducted an age
      matched cohort study using the US Healthcare and Utilization project-Nationwide
      Inpatient Sample from 2003-2011. We used unconditional logistic regression,
      adjusted for baseline characteristics, to estimate the likelihood of common
      obstetric complications in the LT group compared with age-matched nontransplant
      patients. RESULTS: There were 7 288 712 deliveries and an estimated incidence of
      2.1 LTs/100 000 deliveries over the nine-year study period. LT patients had
      higher rates of maternal complications including hypertensive disorders (OR 6.5,
      95% CI: 4.4-9.5), gestational diabetes (OR 1.9, 95% CI: 1.0-3.5), anemia (OR 3.2,
      95% CI: 2.1-4.9), thrombocytopenia (OR 27.5, 95% CI: 12.7-59.8) and genitourinary
      tract infections (OR 4.2, 95% CI: 1.8-9.8). Deliveries among women with LT had
      higher risks of cesarean section (OR 2.9, 95% CI: 2.0-4.1), postpartum hemorrhage
      (OR 3.2, 95% CI: 1.7-6.2) and blood transfusion (OR 18.7, 95% CI: 8.5-41.0).
      Fetal complications in LT patients included preterm delivery (OR 4.7, 95% CI: 3.2
      7.0), intrauterine growth restriction (OR 4.1, 95% CI: 2.1-7.7) and congenital
      anomalies (OR 6.0, 95% CI: 1.1-32.0). CONCLUSION: Although pregnancies in LT
      recipients are feasible, they are associated with a high rate of maternal and
      fetal morbidities. Close antenatal surveillance is recommended.

PMID- 27044921
TI  - Global RNA recognition patterns of post-transcriptional regulators Hfq and CsrA
      revealed by UV crosslinking in vivo.
AB  - The molecular roles of many RNA-binding proteins in bacterial post
      transcriptional gene regulation are not well understood. Approaches combining in
      vivo UV crosslinking with RNA deep sequencing (CLIP-seq) have begun to
      revolutionize the transcriptome-wide mapping of eukaryotic RNA-binding protein
      target sites. We have applied CLIP-seq to chart the target landscape of two major
      bacterial post-transcriptional regulators, Hfq and CsrA, in the model pathogen
      Salmonella Typhimurium. By detecting binding sites at single-nucleotide
      resolution, we identify RNA preferences and structural constraints of Hfq and
      CsrA during their interactions with hundreds of cellular transcripts. This
      reveals 3'-located Rho-independent terminators as a universal motif involved in
      Hfq-RNA interactions. Additionally, Hfq preferentially binds 5' to sRNA-target
      sites in mRNAs, and 3' to seed sequences in sRNAs, reflecting a simple logic in
      how Hfq facilitates sRNA-mRNA interactions. Importantly, global knowledge of Hfq
      sites significantly improves sRNA-target predictions. CsrA binds AUGGA sequences
      in apical loops and targets many Salmonella virulence mRNAs. Overall, our generic
      CLIP-seq approach will bring new insights into post-transcriptional gene
      regulation by RNA-binding proteins in diverse bacterial species.

PMID- 27044923
TI  - The cardiac pathology of non-natural (forensic) deaths.

PMID- 27044924
TI  - Sample pooling as an effective way of simultaneous analysis of new designer drugs
      together with synthetic cannabinoids in human serum provided by therapy and
      forensic psychiatric centres.

PMID- 27044925
TI  - Different aspects of driving under the influence of benzodiazepines.

PMID- 27044927
TI  - Design and synthesis of a novel fluorescent benzo[g]imidazo[4,5-c]quinoline
      nucleoside for monitoring base-pair-induced protonation with cytosine:
      distinguishing cytosine via changes in the intensity and wavelength of
      fluorescence.
AB  - A novel fluorescent benzo[g]imidazo[4,5-c]quinoline nucleoside (BIQ)A (1)
      comprising a 3-deaza-2'-deoxyadenosine skeleton was developed and used to monitor
      (BIQ)A-C base-pair formation in oligodeoxynucleotide (ODN) duplexes. The newly
      synthesized (BIQ)A exhibited distinct photophysical properties associated with
      its protonated/deprotonated forms (monomer: pKa 6.2) via dramatic changes in its
      absorption and fluorescence spectra. In ODN duplexes, the induced protonation of
      (BIQ)A occurred, even under alkalescent conditions when cytosine was the opposite
      base on the complementary strand; the resulting (BIQ)A-C base pairs were stable.
      By monitoring the protonation of (BIQ)A under neutral and alkalescent conditions,
      we could clearly discriminate cytosine through spectral changes in absorption and
      fluorescence. Similarly, we found that the demonstrated 3-deaza-2'-deoxyadenosine
      (3z)A forms a stable base pair with cytosine via N(1) protonation in ODN duplexes
      under neutral and acidic conditions (pH < 7.0). At lower pH values, (3z)A
      containing ODNs could clearly discriminate cytosine through melting temperature
      (Tm) measurements. Therefore, ODN probes containing indicator nucleosides, such
      as (BIQ)A and (3z)A, exhibit great potential as bioprobes for genetic analysis
      and structural studies of nucleic acids. 

PMID- 27044928
TI  - Restraints in daily care for people with moderate intellectual disabilities.
AB  - BACKGROUND: Self-determination is an important factor in improving the quality of
      life of people with moderate intellectual disabilities. A focus on self
      determination implies that restraints on the freedom of people with intellectual
      disabilities should be decreased. In addition, according to the Dutch Care and
      Coercion bill, regular restraints of freedom, such as restrictions on choice of
      food or whom to visit, should be discouraged. Such restraints are only allowed if
      there is the threat of serious harm for the clients or their surroundings.
      RESEARCH QUESTION: What do support staff consider as restraints on freedom and
      how do they justify these restraints? RESEARCH DESIGN: In this study, data were
      collected by semi-structured interviews. Participants and research context:
      Fifteen support staff working with clients with moderate intellectual
      disabilities were interviewed. All participants work within the same organisation
      for people with intellectual disabilities in the Eastern part of the Netherlands.
      Ethical considerations: The study was conducted according to good scientific
      inquiry guidelines and ethical approval was obtained from a university ethics
      committee. FINDINGS: Most restraints of freedom were found to be centred around
      the basic elements in the life of the client, such as eating, drinking and
      sleeping. In justifying these restraints, support staff said that it was
      necessary to give clarity in what clients are supposed to do, to structure their
      life and to keep them from danger. DISCUSSION: In the justification of restraints
      of freedom two ethical viewpoints, a principle-guided approach and an ethics of
      care approach, are opposing one other. Here, the self-determination theory can be
      helpful, while it combines the autonomy of the client, relatedness to others and
      the client's competence. CONCLUSION: Despite the reasonable grounds support staff
      gave for restraining, it raises the question whether restraints of freedom are
      always in the interest of the client.

PMID- 27044929
TI  - PDF text classification to leverage information extraction from publication
      reports.
AB  - OBJECTIVES: Data extraction from original study reports is a time-consuming,
      error-prone process in systematic review development. Information extraction (IE)
      systems have the potential to assist humans in the extraction task, however
      majority of IE systems were not designed to work on Portable Document Format
      (PDF) document, an important and common extraction source for systematic review.
      In a PDF document, narrative content is often mixed with publication metadata or
      semi-structured text, which add challenges to the underlining natural language
      processing algorithm. Our goal is to categorize PDF texts for strategic use by IE
      systems. METHODS: We used an open-source tool to extract raw texts from a PDF
      document and developed a text classification algorithm that follows a multi-pass
      sieve framework to automatically classify PDF text snippets (for brevity, texts)
      into TITLE, ABSTRACT, BODYTEXT, SEMISTRUCTURE, and METADATA categories. To
      validate the algorithm, we developed a gold standard of PDF reports that were
      included in the development of previous systematic reviews by the Cochrane
      Collaboration. In a two-step procedure, we evaluated (1) classification
      performance, and compared it with machine learning classifier, and (2) the
      effects of the algorithm on an IE system that extracts clinical outcome mentions.
      RESULTS: The multi-pass sieve algorithm achieved an accuracy of 92.6%, which was
      9.7% (p<0.001) higher than the best performing machine learning classifier that
      used a logistic regression algorithm. F-measure improvements were observed in the
      classification of TITLE (+15.6%), ABSTRACT (+54.2%), BODYTEXT (+3.7%),
      SEMISTRUCTURE (+34%), and MEDADATA (+14.2%). In addition, use of the algorithm to
      filter semi-structured texts and publication metadata improved performance of the
      outcome extraction system (F-measure +4.1%, p=0.002). It also reduced of number
      of sentences to be processed by 44.9% (p<0.001), which corresponds to a
      processing time reduction of 50% (p=0.005). CONCLUSIONS: The rule-based multi
      pass sieve framework can be used effectively in categorizing texts extracted from
      PDF documents. Text classification is an important prerequisite step to leverage
      information extraction from PDF documents.

PMID- 27044930
TI  - A novel web informatics approach for automated surveillance of cancer mortality
      trends.
AB  - Cancer surveillance data are collected every year in the United States via the
      National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology
      and End Results (SEER) Program of the National Cancer Institute (NCI). General
      trends are closely monitored to measure the nation's progress against cancer. The
      objective of this study was to apply a novel web informatics approach for
      enabling fully automated monitoring of cancer mortality trends. The approach
      involves automated collection and text mining of online obituaries to derive the
      age distribution, geospatial, and temporal trends of cancer deaths in the US.
      Using breast and lung cancer as examples, we mined 23,850 cancer-related and
      413,024 general online obituaries spanning the timeframe 2008-2012. There was
      high correlation between the web-derived mortality trends and the official
      surveillance statistics reported by NCI with respect to the age distribution
      (rho=0.981 for breast; rho=0.994 for lung), the geospatial distribution
      (rho=0.939 for breast; rho=0.881 for lung), and the annual rates of cancer deaths
      (rho=0.661 for breast; rho=0.839 for lung). Additional experiments investigated
      the effect of sample size on the consistency of the web-based findings. Overall,
      our study findings support web informatics as a promising, cost-effective way to
      dynamically monitor spatiotemporal cancer mortality trends.

PMID- 27044931
TI  - Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in
      Patients With ERBB Alterations.
AB  - PURPOSE: Somatic mutations and copy number variation in the ERBB family are
      frequent in urothelial carcinoma (UC) and may represent viable therapeutic
      targets. We studied whether afatinib (an oral, irreversible inhibitor of the ErbB
      family) has activity in UC and if specific ERBB molecular alterations are
      associated with clinical response. PATIENTS AND METHODS: In this phase II trial,
      patients with metastatic platinum-refractory UC received afatinib 40 mg/day
      continuously until progression or intolerance. The primary end point was 3-month
      progression-free survival (PFS3). Prespecified tumor analysis for alterations in
      EGFR, HER2, ERBB3, and ERBB4 was conducted. RESULTS: The first-stage enrollment
      goal of 23 patients was met. Patient demographic data included: 78% male, median
      age 67 years (range, 36 to 82 years), hemoglobin < 10 g/dL in 17%, liver
      metastases in 30%, median time from prior chemotherapy of 3.6 months, and Eastern
      Cooperative Oncology Group performance status <= 1 in 100%. No unexpected
      toxicities were observed; two patients required dose reduction for grade 3
      fatigue and rash. Overall, five of 23 patients (21.7%) met PFS3 (two partial
      response, three stable disease). Notably, among the 21 tumors analyzed, five of
      six patients (83.3%) with HER2 and/or ERBB3 alterations achieved PFS3 (PFS =
      10.3, 7.0, 6.9, 6.3, and 5.0 months, respectively) versus none of 15 patients
      without alterations (P < .001). Three of four patients with HER2 amplification
      and three of three patients with ERBB3 somatic mutations (G284R, V104M, and
      R103G) met PFS3. One patient with both HER2 amplification and ERBB3 mutation
      never progressed on therapy, but treatment was discontinued after 10.3 months as
      a result of depressed ejection fraction. The median time to
      progression/discontinuation was 6.6 months in patients with HER2/ERBB3
      alterations versus 1.4 months in patients without alterations (P < .001).
      CONCLUSION: Afatinib demonstrated significant activity in patients with platinum
      refractory UC with HER2 or ERBB3 alterations. The potential contribution of ERBB3
      to afatinib sensitivity is novel. Afatinib deserves further investigation in
      molecularly selected UC.

PMID- 27044932
TI  - A Rosier Picture for Young Women With Breast Cancer.

PMID- 27044933
TI  - A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or
      Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive
      Local Therapy.
AB  - PURPOSE: Patients with recurrent prostate cancer after local treatment make up a
      heterogeneous population for whom androgen deprivation therapy (ADT) is the usual
      treatment. The purpose of this randomized phase II trial was to investigate the
      efficacy and toxicity of short-course ADT with or without bevacizumab in men with
      hormone-sensitive prostate cancer. PATIENTS AND METHODS: Eligible patients had an
      increasing prostate-specific antigen (PSA) of <= 50 ng/mL and PSA doubling time
      of less than 18 months. Patients had either no metastases or low burden,
      asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases).
      Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone
      agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end
      point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more
      than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for
      primary radiation therapy patients. RESULTS: Sixty-six patients received ADT +
      bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a
      statistically significant improvement in RFS compared with patients treated with
      ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard
      ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most
      common adverse event in patients receiving ADT + bevacizumab (36%). CONCLUSION:
      ADT combined with bevacizumab resulted in an improved RFS for patients with
      hormone-sensitive prostate cancer. Long-term follow-up is needed to determine
      whether some patients have a durable PSA response and are able to remain off ADT
      for prolonged periods. Our data provide rationale for combining vascular
      endothelial growth factor-targeting therapy with ADT in hormone-sensitive
      prostate cancer.

PMID- 27044934
TI  - Vitamin D and Melanoma: What Do We Tell Our Patients?

PMID- 27044935
TI  - Randomized Phase III Noninferiority Study Comparing Two Radiotherapy
      Fractionation Schedules in Patients With Low-Risk Prostate Cancer.
AB  - PURPOSE: Conventional radiotherapy (C-RT) treatment schedules for patients with
      prostate cancer typically require 40 to 45 treatments that take place from > 8 to
      9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer
      treatments but at a higher dose per treatment-may produce similar outcomes. This
      trial was designed to assess whether the efficacy of a hypofractionated
      radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men
      with low-risk prostate cancer. PATIENTS AND METHODS: A total of 1,115 men with
      low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41
      fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This
      trial was designed to establish (with 90% power and an alpha of .05) that
      treatment with H-RT results in 5-year disease-free survival (DFS) that is not
      worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). RESULTS:
      A total of 1,092 men were protocol eligible and had follow-up information; 542
      patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years.
      Baseline characteristics were not different according to treatment assignment.
      The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and
      86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64
      to 1.14), and the predefined noninferiority criterion that required that DFS
      outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI
      and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients
      who were treated with H-RT. CONCLUSION: In men with low-risk prostate cancer, the
      efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41
      fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse
      events was observed in patients treated with H-RT.

PMID- 27044936
TI  - Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With
      Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative
      Early Breast Cancer: TEXT and SOFT Trials.
AB  - PURPOSE: Risk of recurrence is the primary consideration in breast cancer
      adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and
      SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant
      endocrine therapies for premenopausal women with hormone receptor-positive breast
      cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen
      plus OFS, and tamoxifen alone. We examined absolute treatment effect across a
      continuum of recurrence risk to individualize endocrine therapy decision making
      for premenopausal women with human epidermal growth factor receptor 2 (HER2) 
      negative disease. PATIENTS AND METHODS: The TEXT and SOFT hormone receptor
      positive, HER2-negative analysis population included 4,891 women. The end point
      was breast cancer-free interval (BCFI), defined as time from random assignment to
      first occurrence of invasive locoregional, distant, or contralateral breast
      cancer. A continuous, composite measure of recurrence risk for each patient was
      determined from a Cox model incorporating age, nodal status, tumor size and
      grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels.
      Subpopulation treatment effect pattern plot methodology revealed differential
      treatment effects on 5-year BCFI according to composite risk. RESULTS: SOFT
      patients who remained premenopausal after chemotherapy experienced absolute
      improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus
      tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to
      high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was
      apparent at the highest composite risk. The SOFT no-chemotherapy cohort-for whom
      composite risk was lowest on average-did well with all endocrine therapies. For
      TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5
      year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with
      lowest composite risk did well with both treatments. CONCLUSION: Premenopausal
      women with hormone receptor-positive, HER2-negative disease and high recurrence
      risk, as defined by clinicopathologic characteristics, may experience improvement
      of 10% to 15% in 5-year BCFI with exemestane plus OFS versus tamoxifen alone. An
      improvement of at least 5% may be achieved for women at intermediate risk, and
      improvement is minimal for those at lowest risk.

PMID- 27044937
TI  - Cancer and Fertility Program Improves Patient Satisfaction With Information
      Received.
AB  - PURPOSE: A cancer and fertility program was established at a large cancer center
      to support clinicians in discussing treatment-related fertility risks and
      fertility preservation (FP) options with patients and in referring patients to
      reproductive specialists. The program provides resources, clinician education,
      and fertility clinical nurse specialist consultation. This study evaluated the
      program's impact on patient satisfaction with information received. PATIENTS AND
      METHODS: Retrospective cross-sectional surveys assessed satisfaction before
      (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were
      investigator-designed, gender-specific, and anonymous. RESULTS: Most C1 (150
      males, 271 females) and C2 (120 males, 320 females) respondents were 2 years
      postdiagnosis; the most frequently reported cancers were testicular, breast, and
      lymphoma. A significant difference in satisfaction with the amount of information
      received was seen between C1 and C2. For males, satisfaction with information on
      fertility risks was high in both cohorts but significantly greater in C2 for
      information on sperm banking (chi(2) = 9.3, P = .01) and finding a sperm bank
      (chi(2) = 13.3, P = .001). For females, satisfaction with information was
      significantly greater in C2 for information on fertility risks (chi(2) = 62.1, P
      < .001), FP options (chi(2) = 71.9, P < .001), help with decision making (chi(2)
      = 80.2, P < .001), and finding a reproductive endocrinologist (chi(2) = 60.5, P <
      .001). Among patients who received and read information materials, 96% of males
      and 99% of females found them helpful. Among C2 females, fertility clinical nurse
      specialist consultation was associated with significantly greater satisfaction
      with information on FP options (chi(2) = 11.2, P = .004), help with decision
      making (chi(2) = 10.4, P = .006), and finding a reproductive endocrinologist
      (chi(2) = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for
      not pursuing FP. CONCLUSION: Improvements in patient satisfaction with
      information received demonstrate the potential for fertility programs in cancer
      care settings to improve the quality of clinician-patient discussions about
      fertility.

PMID- 27044938
TI  - Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With
      Advanced Cancer.
AB  - PURPOSE: The primary objective was to determine safety, toxicity, and a
      recommended phase II dose regimen of LY2606368, an inhibitor of checkpoint kinase
      1, as monotherapy. PATIENTS AND METHODS: This phase I, nonrandomized, open-label,
      dose-escalation trial used a 3 + 3 dose-escalation scheme and included patients
      with advanced solid tumors. Intravenous LY2606368 was dose escalated from 10 to
      50 mg/m(2) on schedule 1 (days 1 to 3 every 14 days) or from 40 to 130 mg/m(2) on
      schedule 2 (day 1 every 14 days). Safety measures and pharmacokinetics were
      assessed, and pharmacodynamics were measured in blood, hair follicles, and
      circulating tumor cells. RESULTS: Forty-five patients were treated; seven
      experienced dose-limiting toxicities (all hematologic). The maximum-tolerated
      doses (MTDs) were 40 mg/m(2) (schedule 1) and 105 mg/m(2) (schedule 2). The most
      common related grade 3 or 4 treatment-emergent adverse events were neutropenia,
      leukopenia, anemia, thrombocytopenia, and fatigue. Grade 4 neutropenia occurred
      in 73.3% of patients and was transient (typically < 5 days). Febrile neutropenia
      incidence was low (7%). The LY2606368 exposure over the first 72 hours (area
      under the curve from 0 to 72 hours) at the MTD for each schedule coincided with
      the exposure in mouse xenografts that resulted in maximal tumor responses. Minor
      intra- and intercycle accumulation of LY2606368 was observed at the MTDs for both
      schedules. Two patients (4.4%) had a partial response; one had squamous cell
      carcinoma (SCC) of the anus and one had SCC of the head and neck. Fifteen
      patients (33.3%) had a best overall response of stable disease (range, 1.2 to 6.7
      months), six of whom had SCC. CONCLUSION: An LY2606368 dose of 105 mg/m(2) once
      every 14 days is being evaluated as the recommended phase II dose in dose
      expansion cohorts for patients with SCC.

PMID- 27044939
TI  - Future of Hepatocellular Carcinoma Incidence in the United States Forecast
      Through 2030.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) incidence rates have been increasing in
      the United States for the past 35 years. Because HCC has a poor prognosis,
      quantitative forecasts could help to inform prevention and treatment strategies
      to reduce the incidence and burden of HCC. METHODS: Single-year HCC incident case
      and population data for the years 2000 to 2012 and ages 35 to 84 years were
      obtained from the SEER 18 Registry Database. We forecast incident HCC cases
      through 2030, using novel age-period-cohort models and stratifying by sex,
      race/ethnicity, and age. Rates are presented because absolute numbers may be
      influenced by population increases. RESULTS: Rates of HCC increased with each
      successive birth cohort through 1959. However, rates began to decrease with the
      1960 to 1969 birth cohorts. Asians/Pacific Islanders (APIs) have had the highest
      HCC rates in the United States for many years, but the rates have stabilized and
      begun to decline in recent years. Between 2013 and 2030, rates among APIs are
      forecast to decline further, with estimated annual percentage changes of -1.59%
      among men and -2.20% among women. Thus, by 2030, Asians are forecast to have the
      lowest incidence rates among men, and Hispanics are forecast to have the highest
      rates among men (age-standardized rate, 44.2). Blacks are forecast to have the
      highest rate among women (age-standardized rate, 12.82). CONCLUSION: Although
      liver cancer has long had some of the most rapidly increasing incidence rates,
      the decreasing rates seen among APIs, individuals younger than 65 years, and
      cohorts born after 1960 suggest that there will be declines in incidence of HCC
      in future years. Prevention efforts should be focused on individuals in the 1950
      to 1959 birth cohorts, Hispanics, and blacks.

PMID- 27044941
TI  - Evaluation of the effects of platelet-rich fibrin and piezosurgery on outcomes
      after removal of impacted mandibular third molars.
AB  - We compared postoperative outcomes after the removal of 80 impacted mandibular
      third molars in 59 patients. In the control group, osteotomies were done with
      traditional burs (n=20). The second group had traditional osteotomies and
      platelet-rich fibrin (PRF) placed into the socket of the extracted tooth (n=20).
      The third group had piezosurgery (n=20), and the fourth had piezosurgery and PRF
      placed in the extraction socket (n=20). Baseline variables were assessed
      preoperatively and included pain, the number of analgesics taken, trismus, and
      swelling. These were also assessed on postoperative days 1, 2, 3, and 7. There
      was a significant reduction (p<0.05) in pain on days 1, 2, and 3, and in the
      number of analgesics taken on days 2 and 3 in both PRF groups. However, in the
      piezosurgery alone group this was the case only on day 3. There was no
      significant difference in swelling and trismus between the control and other
      groups. 

PMID- 27044940
TI  - Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic
      Hematopoietic Cell Transplantation for Myelodysplastic Syndrome.
AB  - PURPOSE: To develop a system prognostic of outcome in those undergoing allogeneic
      hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS).
      PATIENTS AND METHODS: We examined 2,133 patients with MDS undergoing HLA-matched
      (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox
      multivariable model to identify factors prognostic of mortality in a training
      subset (n = 1,151) of the HLA-matched cohort. A weighted score using these
      factors was assigned to the remaining patients undergoing HLA-matched allo HCT
      (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched
      allo HCT. RESULTS: Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI,
      1.08 to 1.85), platelets 50 * 10(9)/L or less at transplantation (HR, 1.37; 95%
      CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI,
      1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR,
      1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to
      2.35) were associated with increased hazard of death and assigned 1 point in the
      scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50
      years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3
      year overall survival after transplantation in patients with low (0 to 1 points),
      intermediate (2 to 3), high (4 to 5) and very high (>= 6) scores was 71% (95% CI,
      58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI,
      4% to 46%), respectively (P < .001). Increasing score was predictive of increased
      relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched
      set and relapse (P < .001) in the HLA-mismatched cohort. CONCLUSION: The proposed
      system is prognostic of outcome in patients undergoing HLA-matched and 
      mismatched allo HCT for MDS.

PMID- 27044942
TI  - Fate of Multimeric Oligomers, Submicron, and Micron Size Aggregates of Monoclonal
      Antibodies Upon Subcutaneous Injection in Mice.
AB  - The aim of this study was to examine the fate of differently sized protein
      aggregates upon subcutaneous injection in mice. A murine and a human monoclonal
      immunoglobulin G 1 (IgG1) antibody were labeled with a fluorescent dye and
      subjected to stress conditions to create aggregates. Aggregates fractionated by
      centrifugation or gel permeation chromatography were administered subcutaneously
      into SKH1 mice. The biodistribution was measured by in vivo fluorescence imaging
      for up to 1 week post injection. At several time points, mice were sacrificed and
      selected organs and tissues were collected for ex vivo analysis. Part of injected
      aggregated IgGs persisted much longer at the injection site than unstressed
      controls. Aggregate fractions containing submicron (0.1-1 MUm) or micron (1-100
      MUm) particles were retained to a similar extent. Highly fluorescent "hot-spots"
      were detected 24 h post injection in spleens of mice injected with submicron
      aggregates of murine IgG. Submicron aggregates of human IgG showed higher
      accumulation in draining lymph nodes 1 h post injection than unstressed controls
      or micron size aggregates. For both tested proteins, aggregated fractions seemed
      to be eliminated from circulation more rapidly than monomeric fractions. The
      biodistribution of monomers isolated from solutions subjected to stress
      conditions was similar to that of unstressed control.

PMID- 27044943
TI  - Process and Formulation Effects on Protein Structure in Lyophilized Solids Using
      Mass Spectrometric Methods.
AB  - Myoglobin (Mb) was lyophilized in the absence (Mb-A) and presence (Mb-B) of
      sucrose in a pilot-scale lyophilizer with or without controlled ice nucleation.
      Cake morphology was characterized using scanning electron microscopy, and changes
      in protein structure were monitored using solid-state Fourier-transform infrared
      spectroscopy, solid-state hydrogen-deuterium exchange-mass spectrometry, and
      solid-state photolytic labeling-mass spectrometry (ssPL-MS). The results showed
      greater variability in nucleation temperature and irregular cake structure for
      formulations lyophilized without controlled nucleation. Controlled nucleation
      resulted in nucleation at ~(-5 degrees C) and uniform cake structure.
      Formulations containing sucrose showed better retention of protein structure by
      all measures than formulations without sucrose. Samples lyophilized with and
      without controlled nucleation were similar by most measures of protein structure.
      However, ssPL-MS showed the greatest photoleucine incorporation and more labeled
      regions for Mb-B lyophilized with controlled nucleation. The data support the use
      of solid-state hydrogen-deuterium exchange-mass spectrometry and ssPL-MS to study
      formulation and process-induced conformational changes in lyophilized proteins.

PMID- 27044945
TI  - Evaluation of the Intestinal Colonizing Potential and Immunomodulating Capacity
      of Lactobacilli Microspheres.
AB  - Lactobacilli species get degraded by acidic conditions in the stomach. Thus, the
      objective of this study was to (1) formulate and characterize gastro-resistant
      Lactobacilli microspheres and (2) evaluate the ability of Lactobacilli
      microspheres to colonize the intestine and their capacity to have an
      immunomodulating effect in vivo. The product yield and the encapsulation
      efficiency were 45% and 100%, respectively. The average microsphere particle size
      was 5 MUm. Lactobacilli microspheres were most stable at 4 degrees C and showed a
      better suspendibility in distilled water. Without encapsulation, the viability of
      bacteria decreased within 30 min. In the case of Lactobacilli microspheres, no
      Lactobacilli were released in the first 3 h, and highest release was observed at
      4 h, thus, suggesting the significance of encapsulation of Lactobacilli.
      Lactobacilli microspheres maintained intestinal colonization only during the
      dosing period, and the serum IgG, serum IgA, fecal, intestinal, nasal IgA, and
      the serum interleukin-1beta levels were higher in the Lactobacilli microsphere
      group compared with the blank microsphere and the lactobacilli solution group,
      suggesting that the Lactobacilli microspheres were more gastro-resistant and,
      hence, showed positive effects compared with the Lactobacilli solution. However,
      the Lactobacilli microspheres did not have a significant effect on the tumor
      necrosis factor-alpha levels.

PMID- 27044944
TI  - Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges.
AB  - The success of clinical and commercial therapeutic proteins is rapidly
      increasing, but their potential immunogenicity is an ongoing concern. Most of the
      studies that have been conducted over the past few years to examine the
      importance of various product-related attributes (in particular several types of
      aggregates and particles) and treatment regimen (such as dose, dosing schedule,
      and route of administration) in the development of unwanted immune responses have
      utilized one of a variety of mouse models. In this review, we discuss the utility
      and drawbacks of different mouse models that have been used for this purpose.
      Moreover, we summarize the lessons these models have taught us and some of the
      challenges they present. Finally, we provide recommendations for future research
      utilizing mouse models to improve our understanding of critical factors that may
      contribute to protein immunogenicity.

PMID- 27044946
TI  - Formation Rate-Limited Pharmacokinetics of Biologically Active Epoxy Transformers
      of Prodrug Treosulfan.
AB  - A prodrug treosulfan (TREO) is being evaluated in clinical trials as a
      myeloablative agent before hematopoietic stem cell transplantation. The active
      derivatives of TREO, monoepoxide (EBDM), and diepoxide (DEB) are formed in a pH
      dependent nonenzymatic reaction. The aim of the study was to investigate
      pharmacokinetics of the TREO epoxy transformers in a rabbit model and explain the
      causes of low plasma concentrations of EBDM and DEB observed in patients
      receiving high-dose TREO before hematopoietic stem cell transplantation. New
      Zealand white rabbits (n = 5 per cohort) received an intravenous infusion of TREO
      (group I), injection of DEB (group II), and injection of a solution containing
      EBDM (group III). When EBDM and DEB were administered to the rabbits, they
      underwent a very rapid elimination (half-life 0.069 and 0.046 h) associated with
      a high systemic clearance (10.0 and 14.0 L h(-1) kg(-1)). After administration of
      TREO, the t1/2 of EBDM was statistically equal to the t1/2 of the prodrug (1.6
      h). To conclude, after administration of TREO, its epoxy transformers demonstrate
      a formation-limited elimination. Then EBDM and DEB have the same elimination half
      life as TREO, but the levels of EBDM and DEB in the body, including plasma, are
      much lower than TREO on account of their inherently high clearance.

PMID- 27044947
TI  - 'Down-triage' for children with abnormal vital signs: evaluation of a new triage
      practice at a paediatric emergency department in Japan.
AB  - OBJECTIVE: Assessment of abnormal vital signs in triage is a challenge in the
      paediatric emergency department (PED), since vital signs may reflect anxiety,
      fever or pain rather than the clinical deterioration of the child. We aimed to
      evaluate the efficacy of subjective 'down-triage' (change of the initially
      determined acuity levels) of Japanese Triage and Acuity Scale (JTAS). METHODS:
      This is a retrospective cohort study of patients in PED up to 15 years of age at
      a tertiary paediatric medical centre in Japan during a 1-year period. At the end
      of every JTAS triage process, PED nurses were allowed to 'down-triage' acuity
      levels of well-appearing patients with abnormal HR or RR, which were presumably
      attributable to fever, crying or being upset. We compared predictive performance
      of the triage system before and after 'down-triage' using admission rate as the
      primary outcome. RESULTS: Among 37 961 PED visits during the study period, we
      analysed 37 219 records. A total of 17 089 patients (45.9%) were 'down-triaged'
      after their initial triage allocation upon arrival. Admission rates after 'down
      triage' (83%, 33%, 7%, 1% and 3% for levels 1-5, respectively), compared with
      those of unmodified initial level (16%, 11%, 6%, 2% and 6% for levels 1-5,
      respectively), had a better apparent relevance with the anticipated admission
      rates of Canadian Triage and Acuity Scale. CONCLUSIONS: Modification of JTAS
      through 'down-triage' by experienced staff improves prediction of disposition in
      a PED. Further research is needed to determine an objective protocol for 'down
      triage' to ensure safe practice in a PED.

PMID- 27044948
TI  - Intractable vomiting: diagnostic clues in plain neck films.

PMID- 27044949
TI  - Patient and public involvement in emergency care research.
AB  - Patients participate in emergency care research and are the intended
      beneficiaries of research findings. The public provide substantial funding for
      research through taxation and charitable donations. If we do research to benefit
      patients and the public are funding the research, then patients and the public
      should be involved in the planning, prioritisation, design, conduct and oversight
      of research, yet patient and public involvement (or more simply, public
      involvement, since patients are also members of the public) has only recently
      developed in emergency care research. In this article, we describe what public
      involvement is and how it can help emergency care research. We use the
      development of a pioneering public involvement group in emergency care, the
      Sheffield Emergency Care Forum, to provide insights into the potential and
      challenges of public involvement in emergency care research. 

PMID- 27044950
TI  - Procedural sedation and analgesia in the emergency room of a field hospital after
      the Nepal earthquake.
AB  - Procedural sedation and analgesia (PSA) should be a priority in the emergency
      care of injured children. This humanistic approach is particularly important in
      paediatric victims of disaster, because these patients are prone to psychological
      distress secondary to the traumatic event. Following the Nepal earthquake, an
      Israeli field hospital (IFH) was deployed in Kathmandu. We report our experience
      with PSA in the emergency room (ER) of the IFH. 22 children underwent surgery in
      the operating room and 10 underwent PSA in the ER by paediatric emergency
      physicians: 6 had wound debridement, 2 had fracture reduction and 2 had
      laceration repair. All the procedures were successfully completed in the ER and
      no patient required intubation or admission to the intensive care unit due to an
      adverse event. The present study is the first report of the practice of
      paediatric PSA by non-anaesthesiologists in a field hospital. 

PMID- 27044951
TI  - The Patient Engagement Imperative.

PMID- 27044952
TI  - Patients' And Consumers' Use Of Evidence.
AB  - Expectations regarding self-determination in medical care have risen, alongside
      the anticipation of an expanded role for patients as consumers in meeting policy
      goals--such as those surrounding health care costs, quality, and outcomes. These
      expectations are fueled, and potentially supported, by a rise in easily
      accessible information on medical care. For example, numerous government and
      private websites now post online ratings or "report cards" about the quality and
      performance of hospitals, physicians, and nursing homes. Crowdsourced ratings
      (such as Yelp's) are also playing a growing role and even have some power to
      predict results found in official reports. While it is too early to tell if
      consumers' behavior will align with policy goals, researchers have begun to
      explore patients' and consumers' attitudes about the role that medical evidence
      should play in treatment decisions and the relationship between the cost and
      quality of care.

PMID- 27044953
TI  - Understanding An Informed Public's Views On The Role Of Evidence In Making Health
      Care Decisions.
AB  - Policy makers and practitioners increasingly believe that medical evidence plays
      a critical role in improving care and health outcomes and lowering costs.
      However, public understanding of the role of evidence-based care may be
      different. Public deliberation is a process that convenes diverse citizens and
      has them learn about and consider ethical or values-based dilemmas and weigh
      alternative views. The Community Forum Deliberative Methods Demonstration
      project, sponsored by the Agency for Healthcare Research and Quality, obtained
      informed public views on the role of evidence in health care decisions through
      seventy-six deliberative groups involving 907 people overall, in the period
      August-November 2012. Although participants perceived evidence as being essential
      to high-quality care, they also believed that personal choice or clinical
      judgment could trump evidence. They viewed doctors as central figures in
      discussing evidence with patients and key arbiters of whether to follow evidence
      in individual cases. They found evidence of harm to individuals or the community
      to be more compelling than evidence of effectiveness. These findings indicate
      that increased public understanding of evidence can play an important role in
      advancing evidence-based care by helping create policies that better reflect the
      needs and values of the public.

PMID- 27044954
TI  - Incorporating Patient-Reported Outcomes Into Health Care To Engage Patients And
      Enhance Care.
AB  - The provision of patient-centered care requires a health care environment that
      fosters engagement between patients and their health care team. One way to
      encourage patient-centered care is to incorporate patient-reported outcomes into
      clinical settings. Collecting these outcomes in routine care ensures that
      important information only the patient can provide is captured. This provides
      insights into patients' experiences of symptoms, quality of life, and
      functioning; values and preferences; and goals for health care. Previously
      embraced in the research realm, patient-reported outcomes have started to play a
      role in successful shared decision making, which can enhance the safe and
      effective delivery of health care. We examine the opportunities for using patient
      reported outcomes to enhance care delivery and outcomes as health care
      information needs and technology platforms change. We highlight emerging
      practices in which patient-reported outcomes provide value to patients and
      clinicians and improve care delivery. Finally, we examine present and future
      challenges to maximizing the use of patient-reported outcomes in the clinic. 

PMID- 27044955
TI  - The Ethical Imperative And Moral Challenges Of Engaging Patients And The Public
      With Evidence.
AB  - Engaging patients and the public with evidence is an ethical imperative because
      engagement is central to respect for persons and will likely improve health
      outcomes, facilitate the stewardship of resources, enhance prospects for justice,
      and build public trust. However, patient and public engagement is also morally
      complex, because evidence alone is never definitive. As patients and the public
      engage with evidence, value conflicts will arise and must be managed to achieve
      trustworthy decision making. We outline value conflicts likely to emerge in the
      following five settings: clinical care, health care organizations, public health,
      the regulatory context, and among payers. Using a variety of examples, we offer
      suggestions about how such conflicts may be managed, including providing more
      opportunities for democratic deliberation and having more explicit community
      discussion of how to balance personal choice and community well-being,
      transparent discussions of cost and quality outcomes, and greater patient
      engagement in community-based participatory research and the governance of
      learning health systems. 

PMID- 27044956
TI  - Authentic Engagement Of Patients And Communities Can Transform Research,
      Practice, And Policy.
AB  - The engagement of patients and the public is increasingly important in the design
      and conduct of research. Some researchers still cling to the outdated notion that
      laypeople cannot contribute meaningfully to science; for some, "community
      engagement" is another term for recruiting patients for trials. Authentic
      engagement encompasses far more, involving stakeholders as full partners in all
      phases of research, as research funders increasingly require. Such engagement,
      although challenging, can enhance the quality and impact of studies on many
      levels, from ensuring that data are relevant to users' needs to elevating the
      moral plane of research by showing respect to patients and vulnerable
      populations. We share examples from our work, including the engagement of
      patients in a study of cancer screening decisions and the engagement of inner
      city residents in addressing social determinants of health. These engagement
      principles are of growing relevance to health systems and policy makers
      responsible for population health. 

PMID- 27044957
TI  - Patient-Centered Outcomes Research: Early Evidence From A Burgeoning Field.

PMID- 27044958
TI  - Shaping Studies To Meet Patients' Needs.
AB  - In designing new research, academics and funders have begun to solicit feedback
      directly from the populations they plan to study. 

PMID- 27044959
TI  - Enhancing Shared Decision Making Through Carefully Designed Interventions That
      Target Patient And Provider Behavior.
AB  - Patient-provider communication and shared decision making are essential for
      primary care delivery and are vital contributors to patient experience and health
      outcomes. To alleviate communication shortfalls, we designed a novel,
      multidimensional intervention aimed at nudging both patients and primary care
      providers to communicate more openly. The intervention was tested against an
      existing intervention, which focused mainly on changing patients' behaviors, in
      four primary care clinics involving 26 primary care providers and 300 patients.
      Study results suggest that compared to usual care, both the novel and existing
      interventions were associated with better patient reports of how well primary
      care providers engaged them in shared decision making. Future research should
      build on the work in this pilot to rigorously examine the comparative
      effectiveness and scalability of these interventions to improve shared decision
      making at the point of care. 

PMID- 27044960
TI  - Reinventing The Wheel Of Medical Evidence: How The Boot Camp Translation Process
      Is Making Gains.
AB  - Medical guidelines use language and concepts that are not understood by many
      patients, which makes it difficult for patients to choose the best treatment. The
      High Plains Research Network's Community Advisory Council, made up of farmers,
      teachers, and other community members in eastern Colorado, identified a lack of
      community knowledge about colon cancer and developed a process the council named
      Boot Camp Translation to turn complex screening guidelines into locally relevant
      messages. This article provides a brief history of the process and describes how
      it has been used to translate and disseminate evidence-based medical guidelines.
      The Colorado Clinical and Translational Sciences Institute tested the Boot Camp
      Translation process on multiple topics in communities throughout the United
      States from 2012 to 2015. During that period the institute used the process more
      than twenty-five times, addressing the topics of cancer prevention, hypertension,
      asthma, diabetes, and mental health. Multiple studies show that use of the
      process has led to improvement in cancer testing, asthma management, and
      hypertension control. Policies that support the translation of medical evidence
      into local programs will improve the health of patients. 

PMID- 27044961
TI  - A Synthesis Of Knowledge About Caregiver Decision Making Finds Gaps In Support
      For Those Who Care For Aging Loved Ones.
AB  - We conducted a mixed-methods knowledge synthesis to assess the effectiveness of
      interventions to improve caregivers' involvement in decision making with seniors,
      and to describe caregivers' experiences of decision making in the absence of
      interventions. We analyzed forty-nine qualitative, fourteen quantitative, and
      three mixed-methods studies. The qualitative studies indicated that caregivers
      had unmet needs for information, discussions of values and needs, and decision
      support, which led to negative sentiments after decision making. Our results
      indicate that there have been insufficient quantitative evaluations of
      interventions to involve caregivers in decision making with seniors and that the
      evaluations that do exist found few clinically significant effects. Elements of
      usual care that received positive evaluations were the availability of a decision
      coach and a supportive decision-making environment. Additional rigorously
      evaluated interventions are needed to help caregivers be more involved in
      decision making with seniors. 

PMID- 27044962
TI  - Shared Decision Making: The Need For Patient-Clinician Conversation, Not Just
      Information.
AB  - The growth of shared decision making has been driven largely by the understanding
      that patients need information and choices regarding their health care. But while
      these are important elements for patients who make decisions in partnership with
      their clinicians, our experience suggests that they are not enough to address the
      larger issue: the need for the patient and clinician to jointly create a course
      of action that is best for the individual patient and his or her family. The
      larger need in evidence-informed shared decision making is for a patient
      clinician interaction that offers conversation, not just information, and care,
      not just choice. 

PMID- 27044963
TI  - Ten Years, Forty Decision Aids, And Thousands Of Patient Uses: Shared Decision
      Making At Massachusetts General Hospital.
AB  - Shared decision making is a core component of population health strategies aimed
      at improving patient engagement. Massachusetts General Hospital's integration of
      shared decision making into practice has focused on the following three elements:
      developing a culture receptive to, and health care providers skilled in, shared
      decision making conversations; using patient decision aids to help inform and
      engage patients; and providing infrastructure and resources to support the
      implementation of shared decision making in practice. In the period 2005-15, more
      than 900 clinicians and other staff members were trained in shared decision
      making, and more than 28,000 orders for one of about forty patient decision aids
      were placed to support informed patient-centered decisions. We profile two
      different implementation initiatives that increased the use of patient decision
      aids at the hospital's eighteen adult primary care practices, and we summarize
      key elements of the shared decision making program. 

PMID- 27044964
TI  - Connecticut's Value-Based Insurance Plan Increased The Use Of Targeted Services
      And Medication Adherence.
AB  - In 2011 Connecticut implemented the Health Enhancement Program for state
      employees. This voluntary program followed the principles of value-based
      insurance design (VBID) by lowering patient costs for certain high-value primary
      and chronic disease preventive services, coupled with requirements that enrollees
      receive these services. Nonparticipants in the program, including those removed
      for noncompliance with its requirements, were assessed a premium surcharge. The
      program was intended to curb cost growth and improve health through adherence to
      evidence-based preventive care. To evaluate its efficacy in doing so, we compared
      changes in service use and spending after implementation of the program to trends
      among employees of six other states. Compared to employees of other states,
      Connecticut employees were similar in age and sex but had a slightly higher
      percentage of enrollees with chronic conditions and substantially higher spending
      at baseline. During the program's first two years, the use of targeted services
      and adherence to medications for chronic conditions increased, while emergency
      department use decreased, relative to the situation in the comparison states. The
      program's impact on costs was inconclusive and requires a longer follow-up
      period. This novel combination of VBID principles and participation requirements
      may be a tool that can help plan sponsors increase the use of evidence-based
      preventive services. 

PMID- 27044965
TI  - Most Americans Do Not Believe That There Is An Association Between Health Care
      Prices And Quality Of Care.
AB  - Many organizations are developing health care price information tools for
      consumers. However, consumers may avoid low-price care if they perceive price to
      be associated with quality. We conducted a nationally representative survey to
      examine whether consumers perceive that price and quality are associated and
      whether the way in which questions are framed affects consumers' responses. Most
      Americans (58-71 percent, depending on question framing) did not think that price
      and quality are associated, but a substantial minority did perceive an
      association (21-24 percent) or were unsure whether there was one (8-16 percent).
      Responses to questions framed in terms of high price and high quality differed
      from responses to questions framed in terms of low price and low quality. People
      who had compared prices were more likely than those who had not compared prices
      to perceive that price and quality were associated. We explore implications of
      these findings, including how behavioral economics can inform approaches to
      helping consumers use price and quality information.

PMID- 27044966
TI  - Study Of Physician And Patient Communication Identifies Missed Opportunities To
      Help Reduce Patients' Out-Of-Pocket Spending.
AB  - Some experts contend that requiring patients to pay out of pocket for a portion
      of their care will bring consumer discipline to health care markets. But are
      physicians prepared to help patients factor out-of-pocket expenses into medical
      decisions? In this qualitative study of audiorecorded clinical encounters, we
      identified physician behaviors that stand in the way of helping patients navigate
      out-of-pocket spending. Some behaviors reflected a failure to fully engage with
      patients' financial concerns, from never acknowledging such concerns to
      dismissing them too quickly. Other behaviors reflected a failure to resolve
      uncertainty about out-of-pocket expenses or reliance on temporary solutions
      without making long-term plans to reduce spending. Many of these failures
      resulted from systemic barriers to health care spending conversations, such as a
      lack of price transparency. For consumer health care markets to work as intended,
      physicians need to be prepared to help patients navigate out-of-pocket expenses
      when financial concerns arise during clinical encounters. 

PMID- 27044967
TI  - Examining A Health Care Price Transparency Tool: Who Uses It, And How They Shop
      For Care.
AB  - Calls for transparency in health care prices are increasing, in an effort to
      encourage and enable patients to make value-based decisions. Yet there is very
      little evidence of whether and how patients use health care price transparency
      tools. We evaluated the experiences, in the period 2011-12, of an insured
      population of nonelderly adults with Aetna's Member Payment Estimator, a web
      based tool that provides real-time, personalized, episode-level price estimates.
      Overall, use of the tool increased during the study period but remained low.
      Nonetheless, for some procedures the number of people searching for prices of
      services (called searchers) was high relative to the number of people who
      received the service (called patients). Among Aetna patients who had an imaging
      service, childbirth, or one of several outpatient procedures, searchers for price
      information were significantly more likely to be younger and healthier and to
      have incurred higher annual deductible spending than patients who did not search
      for price information. A campaign to deliver price information to consumers may
      be important to increase patients' engagement with price transparency tools.

PMID- 27044968
TI  - Summarized Costs, Placement Of Quality Stars, And Other Online Displays Can Help
      Consumers Select High-Value Health Plans.
AB  - Starting in 2017, all state and federal health insurance exchanges will present
      quality data on health plans in addition to cost information. We analyzed
      variations in the current design of information on state exchanges to identify
      presentation approaches that encourage consumers to take quality as well as cost
      into account when selecting a health plan. Using an online sample of 1,025
      adults, we randomly assigned participants to view the same comparative
      information on health plans, displayed in different ways. We found that consumers
      were much more likely to select a high-value plan when cost information was
      summarized instead of detailed, when quality stars were displayed adjacent to
      cost information, when consumers understood that quality stars signified the
      quality of medical care, and when high-value plans were highlighted with a check
      mark or blue ribbon. These approaches, which were equally effective for
      participants with higher and lower numeracy, can inform the development of future
      displays of plan information in the exchanges. 

PMID- 27044969
TI  - For Third Enrollment Period, Marketplaces Expand Decision Support Tools To Assist
      Consumers.
AB  - The design of the Affordable Care Act's online health insurance Marketplaces can
      improve how consumers make complex health plan choices. We examined the choice
      environment on the state-based Marketplaces and HealthCare.gov in the third open
      enrollment period. Compared to previous enrollment periods, we found greater
      adoption of some decision support tools, such as total cost estimators and
      integrated provider lookups. Total cost estimators differed in how they generated
      estimates: In some Marketplaces, consumers categorized their own utilization,
      while in others, consumers answered detailed questions and were assigned a
      utilization profile. The tools available before creating an account (in the
      window-shopping period) and afterward (in the real-shopping period) differed in
      several Marketplaces. For example, five Marketplaces provided total cost
      estimators to window shoppers, but only two provided them to real shoppers.
      Further research is needed on the impact of different choice environments and on
      which tools are most effective in helping consumers pick optimal plans. 

PMID- 27044970
TI  - Consumers' Interest In Provider Ratings Grows, And Improved Report Cards And
      Other Steps Could Accelerate Their Use.
AB  - Encouraging patients and consumers to use data and other information in choosing
      health care providers is an important way to enhance patient engagement and
      improve the quality of care. The growing use of technology, including smart
      phones and near-ubiquitous Internet access, provides consumers with easy access
      to websites that collect and report assessments and ratings of providers,
      primarily physicians and hospitals. In addition to new technology, recent laws
      and changes in society and the delivery of care are laying the foundation for
      greater use by consumers of provider performance report cards. Such use could be
      accelerated if the shortcomings of current report card efforts were addressed.
      Recommendations include making online report cards easier to use and more
      understandable, engaging, substantive, and relevant to consumers' health and
      medical concerns and choices. 

PMID- 27044971
TI  - Yelp Reviews Of Hospital Care Can Supplement And Inform Traditional Surveys Of
      The Patient Experience Of Care.
AB  - Little is known about how real-time online rating platforms such as Yelp may
      complement the Hospital Consumer Assessment of Healthcare Providers and Systems
      (HCAHPS) survey, which is the US standard for evaluating patients' experiences
      after hospitalization. We compared the content of Yelp narrative reviews of
      hospitals to the topics in the HCAHPS survey, called domains in HCAHPS
      terminology. While the domains included in Yelp reviews covered the majority of
      HCAHPS domains, Yelp reviews covered an additional twelve domains not found in
      HCAHPS. The majority of Yelp topics that most strongly correlate with positive or
      negative reviews are not measured or reported by HCAHPS. The large collection of
      patient- and caregiver-centered experiences found on Yelp can be analyzed with
      natural language processing methods, identifying for policy makers the measures
      of hospital quality that matter most to patients and caregivers. The Yelp
      measures and analysis can also provide actionable feedback for hospitals. 

PMID- 27044972
TI  - Use Of Nursing Home Compare Website Appears Limited By Lack Of Awareness And
      Initial Mistrust Of The Data.
AB  - In December 2008 the Centers for Medicare and Medicaid Services (CMS) launched a
      five-star rating system of nursing homes as part of Nursing Home Compare, a web
      based report card detailing quality of care at all CMS-certified nursing homes.
      Questions remain, however, as to how well consumers use this rating system as
      well as other sources of information in choosing nursing home placement. We used
      a qualitative assessment of how consumers select nursing homes and of the role of
      information about quality, using semistructured interviews of people who recently
      placed a family member or friend in a nursing home. We found that consumers were
      receptive to using Internet-based information about quality as one source of
      information but that choice was limited by the need for specialized services,
      proximity to family or health care providers, and availability of Medicaid beds.
      Consumers had a positive reaction when shown Nursing Home Compare; however, its
      use appeared to be limited by lack of awareness and, to some extent, initial lack
      of trust of the data. Our findings suggest that efforts to expand the use of
      Nursing Home Compare should focus on awareness and trust. Useful additions to
      Nursing Home Compare might include measures of the availability of activities,
      information about cost, and consumer satisfaction.

PMID- 27044973
TI  - When Patients Customize Nursing Home Ratings, Choices And Rankings Differ From
      The Government's Version.
AB  - Report cards currently published by the Centers for Medicare and Medicaid
      Services (CMS) offer composite (summary) quality measures based on a five-star
      ratings system, such as the one featured on the Nursing Home Compare website.
      These ratings are "one size fits all patients" measures. Nursing Home Compare
      Plus is an alternative that allows patients and their families to create their
      own composite scores based on their own preferences and medical needs. We present
      data from 146 patients who were discharged from the hospital to nursing homes who
      used Nursing Home Compare Plus. We found that the individual patient-constructed
      composites differed from CMS's five-star ratings composite. Patients differed
      from each other and from CMS in the number of performance measures they chose to
      include in their composite and in their weighting of each performance measure.
      When comparing Nursing Home Compare Plus to Medicare's five-star ratings, we
      found only minimal agreement on ranking of nursing homes. We conclude that
      patients might benefit if current report cards are modified to include an option
      for personalized ranking. 

PMID- 27044974
TI  - The Importance Of Integrating Narrative Into Health Care Decision Making.
AB  - When making health care decisions, patients and consumers use data but also
      gather stories from family and friends. When advising patients, clinicians
      consult the medical evidence but also use professional judgment. These stories
      and judgments, as well as other forms of narrative, shape decision making but
      remain poorly understood. Furthermore, qualitative research methods to examine
      narrative are rarely included in health science research. We illustrate how
      narratives shape decision making and explain why it is difficult but necessary to
      integrate qualitative research on narrative into the health sciences. We draw on
      social-scientific insights on rigorous qualitative research and our ongoing
      studies of decision making by patients with cancer, and we describe new tools and
      approaches that link qualitative research findings with the predominantly
      quantitative health science scholarship. Finally, we highlight the benefits of
      more fully integrating qualitative research and narrative analysis into the
      medical evidence base and into evidence-based medical practice. 

PMID- 27044975
TI  - One-Sided Social Media Comments Influenced Opinions And Intentions About Home
      Birth: An Experimental Study.
AB  - As people increasingly turn to social media to access and create health evidence,
      the greater availability of data and information ought to help more people make
      evidence-informed health decisions that align with what matters to them. However,
      questions remain as to whether people can be swayed in favor of or against
      options by polarized social media, particularly in the case of controversial
      topics. We created a composite mock news article about home birth from six real
      news articles and randomly assigned participants in an online study to view
      comments posted about the original six articles. We found that exposure to one
      sided social media comments with one-sided opinions influenced participants'
      opinions of the health topic regardless of their reported level of previous
      knowledge, especially when comments contained personal stories. Comments
      representing a breadth of views did not influence opinions, which suggests that
      while exposure to one-sided comments may bias opinions, exposure to balanced
      comments may avoid such bias. 

PMID- 27044976
TI  - Even In An Emergency, Doctors Must Make Informed Consent An Informed Choice.
AB  - When a stroke is suspected, a daughter is pressured to consent to her father's
      treatment without fully understanding the risks. 

PMID- 27044977
TI  - Patient Engagement And Patients' Use Of Evidence.

PMID- 27044980
TI  - Erratum for Ryu et al., Activating and Elucidating Metabolism of Complex Sugars
      in Yarrowia lipolytica.

PMID- 27044982
TI  - Entropy of cardiac repolarization predicts ventricular arrhythmias and mortality
      in patients receiving an implantable cardioverter-defibrillator for primary
      prevention of sudden death.
AB  - AIMS: The need for a readily available, inexpensive, non-invasive method for
      improved risk stratification of heart failure (HF) patients is paramount. Prior
      studies have proposed that distinct fluctuation patterns underlying the
      variability of physiological signals have unique prognostic value. We tested this
      hypothesis in an extensively phenotyped cohort of HF patients using EntropyXQT, a
      novel non-linear measure of cardiac repolarization dynamics. METHODS AND RESULTS:
      In a prospective, multicentre, observational study of 852 patients in sinus
      rhythm undergoing clinically indicated primary prevention implantable
      cardioverter-defibrillator (ICD) implantation (2003-10), exposures included
      demographics, history, physical examination, medications, laboratory results,
      serum biomarkers, ejection fraction, conventional electrocardiographic (ECG)
      analyses of heart rate and QT variability, and EntropyXQT. The primary outcome
      was first 'appropriate' ICD shock for ventricular arrhythmias. The secondary
      outcome was composite events (appropriate ICD shock and all-cause mortality).
      After exclusions, the cohort (n = 816) had a mean age of 60 +/- 13 years, 28%
      women, 36% African Americans, 56% ischaemic cardiomyopathy, and 29 +/- 16%
      Seattle HF risk score (SHFS) 5-year predicted mortality. Over 45 +/- 24 months,
      there were 134 appropriate shocks and 166 deaths. After adjusting for 30
      exposures, the hazard ratios (comparing the 5th to 1st quintile of EntropyXQT)
      for primary and secondary outcomes were 3.29 (95% CI 1.74-6.21) and 2.28 (1.53
      3.41), respectively. Addition of EntropyXQT to a model comprised of the exposures
      or SHFS significantly increased net reclassification and the ROC curve area.
      CONCLUSIONS: EntropyXQT measured during ICD implantation strongly and
      independently predicts appropriate shock and all-cause mortality over follow-up.
      EntropyXQT complements conventional risk predictors and has the potential for
      broad clinical application.

PMID- 27044983
TI  - Discovery and characterisation of a novel toxin from Dendroaspis angusticeps,
      named Tx7335, that activates the potassium channel KcsA.
AB  - Due to their central role in essential physiological processes, potassium
      channels are common targets for animal toxins. These toxins in turn are of great
      value as tools for studying channel function and as lead compounds for drug
      development. Here, we used a direct toxin pull-down assay with immobilised KcsA
      potassium channel to isolate a novel KcsA-binding toxin (called Tx7335) from
      eastern green mamba snake (Dendroaspis angusticeps) venom. Sequencing of the
      toxin by Edman degradation and mass spectrometry revealed a 63 amino acid residue
      peptide with 4 disulphide bonds that belongs to the three-finger toxin family,
      but with a unique modification of its disulphide-bridge scaffold. The toxin
      induces a dose-dependent increase in both open probabilities and mean open times
      on KcsA in artificial bilayers. Thus, it unexpectedly behaves as a channel
      activator rather than an inhibitor. A charybdotoxin-sensitive mutant of KcsA
      exhibits similar susceptibility to Tx7335 as wild-type, indicating that the
      binding site for Tx7335 is distinct from that of canonical pore-blocker toxins.
      Based on the extracellular location of the toxin binding site (far away from the
      intracellular pH gate), we propose that Tx7335 increases potassium flow through
      KcsA by allosterically reducing inactivation of the channel.

PMID- 27044984
TI  - Influence of dormancy on microbial competition under intermittent substrate
      supply: insights from model simulations.
AB  - Most natural environments are characterized by frequent changes of their abiotic
      conditions. Microorganisms can respond to such changes by switching their
      physiological state between activity and dormancy allowing them to endure periods
      of unfavorable abiotic conditions. As a consequence, the competitiveness of
      microbial species is not simply determined by their growth performance under
      favorable conditions but also by their ability and readiness to respond to
      periods of unfavorable environmental conditions. The present study investigates
      the relevance of factors controlling the abundance and activity of individual
      bacterial species competing for an intermittently supplied substrate. For this
      purpose, numerical experiments were performed addressing the response of
      microbial systems to regularly applied feeding pulses. Simulation results show
      that community dynamics may exhibit a non-trivial link to the frequency of the
      external constraints and that for a certain combination of these environmental
      conditions coexistence of species is possible. The ecological implication of our
      results is that even non-dominant, neglected species can have a strong influence
      on realized species composition of dominant key species, due to their invisible
      presence enable the coexistence between important key species and by this
      affecting provided function of the system. 

PMID- 27044985
TI  - Globally conditioned Granger causality in brain-brain and brain-heart
      interactions: a combined heart rate variability/ultra-high-field (7 T) functional
      magnetic resonance imaging study.
AB  - The causal, directed interactions between brain regions at rest (brain-brain
      networks) and between resting-state brain activity and autonomic nervous system
      (ANS) outflow (brain-heart links) have not been completely elucidated. We
      collected 7 T resting-state functional magnetic resonance imaging (fMRI) data
      with simultaneous respiration and heartbeat recordings in nine healthy volunteers
      to investigate (i) the causal interactions between cortical and subcortical brain
      regions at rest and (ii) the causal interactions between resting-state brain
      activity and the ANS as quantified through a probabilistic, point-process-based
      heartbeat model which generates dynamical estimates for sympathetic and
      parasympathetic activity as well as sympathovagal balance. Given the high amount
      of information shared between brain-derived signals, we compared the results of
      traditional bivariate Granger causality (GC) with a globally conditioned approach
      which evaluated the additional influence of each brain region on the causal
      target while factoring out effects concomitantly mediated by other brain regions.
      The bivariate approach resulted in a large number of possibly spurious causal
      brain-brain links, while, using the globally conditioned approach, we
      demonstrated the existence of significant selective causal links between
      cortical/subcortical brain regions and sympathetic and parasympathetic modulation
      as well as sympathovagal balance. In particular, we demonstrated a causal role of
      the amygdala, hypothalamus, brainstem and, among others, medial, middle and
      superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar
      regions in modulating the so-called central autonomic network (CAN). In summary,
      we show that, provided proper conditioning is employed to eliminate spurious
      causalities, ultra-high-field functional imaging coupled with physiological
      signal acquisition and GC analysis is able to quantify directed brain-brain and
      brain-heart interactions reflecting central modulation of ANS outflow. 

PMID- 27044986
TI  - Central- and autonomic nervous system coupling in schizophrenia.
AB  - The autonomic nervous system (ANS) dysfunction has been well described in
      schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between
      the ANS and central brain activity has been not addressed until now in SZ. The
      interactions between the central nervous system (CNS) and ANS need to be
      considered as a feedback-feed-forward system that supports flexible and adaptive
      responses to specific demands. For the first time, to the best of our knowledge,
      this study investigates central-autonomic couplings (CAC) studying heart rate,
      blood pressure and electroencephalogram in paranoid schizophrenic patients,
      comparing them with age-gender-matched healthy subjects (CO). The emphasis is to
      determine how these couplings are composed by the different regulatory aspects of
      the CNS-ANS. We found that CAC were bidirectional, and that the causal influence
      of central activity towards systolic blood pressure was more strongly pronounced
      than such causal influence towards heart rate in paranoid schizophrenic patients
      when compared with CO. In paranoid schizophrenic patients, the central activity
      was a much stronger variable, being more random and having fewer rhythmic
      oscillatory components. This study provides a more in-depth understanding of the
      interplay of neuronal and autonomic regulatory processes in SZ and most likely
      greater insights into the complex relationship between psychotic stages and
      autonomic activity. 

PMID- 27044987
TI  - Spontaneous physiological variability modulates dynamic functional connectivity
      in resting-state functional magnetic resonance imaging.
AB  - It is well known that the blood oxygen level-dependent (BOLD) signal measured by
      functional magnetic resonance imaging (fMRI) is influenced-in addition to
      neuronal activity-by fluctuations in physiological signals, including arterial
      CO2, respiration and heart rate/heart rate variability (HR/HRV). Even spontaneous
      fluctuations of the aforementioned physiological signals have been shown to
      influence the BOLD fMRI signal in a regionally specific manner. Related to this,
      estimates of functional connectivity between different brain regions, performed
      when the subject is at rest, may be confounded by the effects of physiological
      signal fluctuations. Moreover, resting functional connectivity has been shown to
      vary with respect to time (dynamic functional connectivity), with the sources of
      this variation not fully elucidated. In this context, we examine the relation
      between dynamic functional connectivity patterns and the time-varying properties
      of simultaneously recorded physiological signals (end-tidal CO2 and HR/HRV) using
      resting-state fMRI measurements from 12 healthy subjects. The results reveal a
      modulatory effect of the aforementioned physiological signals on the dynamic
      resting functional connectivity patterns for a number of resting-state networks
      (default mode network, somatosensory, visual). By using discrete wavelet
      decomposition, we also show that these modulation effects are more pronounced in
      specific frequency bands.

PMID- 27044988
TI  - Nonlinear effects of respiration on the crosstalk between cardiovascular and
      cerebrovascular control systems.
AB  - Cardiovascular and cerebrovascular regulatory systems are vital control
      mechanisms responsible for guaranteeing homeostasis and are affected by
      respiration. This work proposes the investigation of cardiovascular and
      cerebrovascular control systems and the nonlinear influences of respiration on
      both regulations through joint symbolic analysis (JSA), conditioned or
      unconditioned on respiration. Interactions between cardiovascular and
      cerebrovascular regulatory systems were evaluated as well by performing
      correlation analysis between JSA indexes describing the two control systems.
      Heart period, systolic and mean arterial pressure, mean cerebral blood flow
      velocity and respiration were acquired on a beat-to-beat basis in 13 subjects
      experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non
      SYNC) in supine resting condition and during head-up tilt test at 60 degrees 
      (TILT). Results showed that JSA distinguished conditions and groups, whereas time
      domain parameters detected only the effect of TILT. Respiration affected
      cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was
      able to modulate the interactions between the two control systems with different
      outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the
      impact of respiration on cardiovascular and cerebrovascular regulatory systems
      might improve our understanding of the mechanisms underpinning the development of
      postural-related syncope. 

PMID- 27044989
TI  - Multiple-input nonlinear modelling of cerebral haemodynamics using spontaneous
      arterial blood pressure, end-tidal CO2 and heart rate measurements.
AB  - In order to examine the effect of changes in heart rate (HR) upon cerebral
      perfusion and autoregulation, we include the HR signal recorded from 18 control
      subjects as a third input in a two-input model of cerebral haemodynamics that has
      been used previously to quantify the dynamic effects of changes in arterial blood
      pressure and end-tidal CO2upon cerebral blood flow velocity (CBFV) measured at
      the middle cerebral arteries via transcranial Doppler ultrasound. It is shown
      that the inclusion of HR as a third input reduces the output prediction error in
      a statistically significant manner, which implies that there is a functional
      connection between HR changes and CBFV. The inclusion of nonlinearities in the
      model causes further statistically significant reduction of the output prediction
      error. To achieve this task, we employ the concept of principal dynamic modes
      (PDMs) that yields dynamic nonlinear models of multi-input systems using
      relatively short data records. The obtained PDMs suggest model-driven
      quantitative hypotheses for the role of sympathetic and parasympathetic activity
      (corresponding to distinct PDMs) in the underlying physiological mechanisms by
      virtue of their relative contributions to the model output. These relative PDM
      contributions are subject-specific and, therefore, may be used to assess
      personalized characteristics for diagnostic purposes. 

PMID- 27044990
TI  - Combining electroencephalographic activity and instantaneous heart rate for
      assessing brain-heart dynamics during visual emotional elicitation in healthy
      subjects.
AB  - Emotion perception, occurring in brain areas such as the prefrontal cortex and
      amygdala, involves autonomic responses affecting cardiovascular dynamics.
      However, how such brain-heart dynamics is further modulated by emotional valence
      (pleasantness/unpleasantness), also considering different arousing levels (the
      intensity of the emotional stimuli), is still unknown. To this extent, we
      combined electroencephalographic (EEG) dynamics and instantaneous heart rate
      estimates to study emotional processing in healthy subjects. Twenty-two healthy
      volunteers were elicited through affective pictures gathered from the
      International Affective Picture System. The experimental protocol foresaw 110
      pictures, each of which lasted 10 s, associated to 25 different combinations of
      arousal and valence levels, including neutral elicitations. EEG data were
      processed using short-time Fourier transforms to obtain time-varying maps of
      cortical activation, whereas the associated instantaneous cardiovascular dynamics
      was estimated in the time and frequency domains through inhomogeneous point
      process models. Brain-heart linear and nonlinear coupling was estimated through
      the maximal information coefficient (MIC). Considering EEG oscillations in
      thethetaband (4-8 Hz), MIC highlighted significant arousal-dependent changes
      between positive and negative stimuli, especially occurring at intermediate
      arousing levels through the prefrontal cortex interplay. Moreover, high arousing
      elicitations seem to mitigate changes in brain-heart dynamics in response to
      pleasant/unpleasant visual elicitation. 

PMID- 27044991
TI  - Delay-correlation landscape reveals characteristic time delays of brain rhythms
      and heart interactions.
AB  - Within the framework of 'Network Physiology', we ask a fundamental question of
      how modulations in cardiac dynamics emerge from networked brain-heart
      interactions. We propose a generalized time-delay approach to identify and
      quantify dynamical interactions between physiologically relevant brain rhythms
      and the heart rate. We perform empirical analysis of synchronized continuous EEG
      and ECG recordings from 34 healthy subjects during night-time sleep. For each
      pair of brain rhythm and heart interaction, we construct a delay-correlation
      landscape (DCL) that characterizes how individual brain rhythms are coupled to
      the heart rate, and how modulations in brain and cardiac dynamics are coordinated
      in time. We uncover characteristic time delays and an ensemble of specific
      profiles for the probability distribution of time delays that underly brain-heart
      interactions. These profiles are consistently observed in all subjects,
      indicating a universal pattern. Tracking the evolution of DCL across different
      sleep stages, we find that the ensemble of time-delay profiles changes from one
      physiologic state to another, indicating a strong association with physiologic
      state and function. The reported observations provide new insights on
      neurophysiological regulation of cardiac dynamics, with potential for broad
      clinical applications. The presented approach allows one to simultaneously
      capture key elements of dynamic interactions, including characteristic time
      delays and their time evolution, and can be applied to a range of coupled
      dynamical systems. 

PMID- 27044992
TI  - The pulsatility volume index: an indicator of cerebrovascular compliance based on
      fast magnetic resonance imaging of cardiac and respiratory pulsatility.
AB  - The influence of cardiac activity on the viscoelastic properties of intracranial
      tissue is one of the mechanisms through which brain-heart interactions take
      place, and is implicated in cerebrovascular disease. Cerebrovascular disease risk
      is not fully explained by current risk factors, including arterial compliance.
      Cerebrovascular compliance is currently estimated indirectly through Doppler
      sonography and magnetic resonance imaging (MRI) measures of blood velocity
      changes. In order to meet the need for novel cerebrovascular disease risk
      factors, we aimed to design and validate an MRI indicator of cerebrovascular
      compliance based on direct endogenous measures of blood volume changes. We
      implemented a fast non-gated two-dimensional MRI pulse sequence based on echo
      planar imaging (EPI) with ultra-short repetition time (approx. 30-50 ms), which
      stepped through slices every approximately 20 s. We constrained the solution of
      the Bloch equations for spins moving faster than a critical speed to produce an
      endogenous contrast primarily dependent on spin volume changes, and an
      approximately sixfold signal gain compared with Ernst angle acquisitions achieved
      by the use of a 90 degrees  flip angle. Using cardiac and respiratory peaks
      detected on physiological recordings, average cardiac and respiratory MRI pulse
      waveforms in several brain compartments were obtained at 7 Tesla, and used to
      derive a compliance indicator, the pulsatility volume index (pVI). The pVI,
      evaluated in larger cerebral arteries, displayed significant variation within and
      across vessels. Multi-echo EPI showed the presence of significant pulsatility
      effects in both S0 and [Formula: see text] signals, compatible with blood volume
      changes. Lastly, the pVI dynamically varied during breath-holding compared with
      normal breathing, as expected for a compliance indicator. In summary, we
      characterized and performed an initial validation of a novel MRI indicator of
      cerebrovascular compliance, which might prove useful to investigate brain-heart
      interactions in cerebrovascular disease and other disorders.

PMID- 27044993
TI  - Predictability decomposition detects the impairment of brain-heart dynamical
      networks during sleep disorders and their recovery with treatment.
AB  - This work introduces a framework to study the network formed by the autonomic
      component of heart rate variability (cardiac processeta) and the amplitude of the
      different electroencephalographic waves (brain processes delta, theta, alpha,
      sigma, beta) during sleep. The framework exploits multivariate linear models to
      decompose the predictability of any given target process into measures of self-,
      causal and interaction predictability reflecting respectively the information
      retained in the process and related to its physiological complexity, the
      information transferred from the other source processes, and the information
      modified during the transfer according to redundant or synergistic interaction
      between the sources. The framework is here applied to
      theeta,delta,theta,alpha,sigma,betatime series measured from the sleep recordings
      of eight severe sleep apnoea-hypopnoea syndrome (SAHS) patients studied before
      and after long-term treatment with continuous positive airway pressure (CPAP)
      therapy, and 14 healthy controls. Results show that the full and self
      predictability of eta, delta and theta decreased significantly in SAHS compared
      with controls, and were restored with CPAP fordeltaandthetabut not foreta The
      causal predictability of eta and delta occurred through significantly redundant
      source interaction during healthy sleep, which was lost in SAHS and recovered
      after CPAP. These results indicate that predictability analysis is a viable tool
      to assess the modifications of complexity and causality of the cerebral and
      cardiac processes induced by sleep disorders, and to monitor the restoration of
      the neuroautonomic control of these processes during long-term treatment.

PMID- 27044995
TI  - Uncovering brain-heart information through advanced signal and image processing.
AB  - Through their dynamical interplay, the brain and the heart ensure fundamental
      homeostasis and mediate a number of physiological functions as well as their
      disease-related aberrations. Although a vast number of ad hoc analytical and
      computational tools have been recently applied to the non-invasive
      characterization of brain and heart dynamic functioning, little attention has
      been devoted to combining information to unveil the interactions between these
      two physiological systems. This theme issue collects contributions from leading
      experts dealing with the development of advanced analytical and computational
      tools in the field of biomedical signal and image processing. It includes
      perspectives on recent advances in 7 T magnetic resonance imaging as well as
      electroencephalogram, electrocardiogram and cerebrovascular flow processing, with
      the specific aim of elucidating methods to uncover novel biological and
      physiological correlates of brain-heart physiology and physiopathology. 

PMID- 27044994
TI  - Brain-heart interactions: challenges and opportunities with functional magnetic
      resonance imaging at ultra-high field.
AB  - Magnetic resonance imaging (MRI) at ultra-high field (UHF) strengths (7 T and
      above) offers unique opportunities for studying the human brain with increased
      spatial resolution, contrast and sensitivity. However, its reliability can be
      compromised by factors such as head motion, image distortion and non-neural
      fluctuations of the functional MRI signal. The objective of this review is to
      provide a critical discussion of the advantages and trade-offs associated with
      UHF imaging, focusing on the application to studying brain-heart interactions. We
      describe how UHF MRI may provide contrast and resolution benefits for measuring
      neural activity of regions involved in the control and mediation of autonomic
      processes, and in delineating such regions based on anatomical MRI contrast.
      Limitations arising from confounding signals are discussed, including challenges
      with distinguishing non-neural physiological effects from the neural signals of
      interest that reflect cardiorespiratory function. We also consider how recently
      developed data analysis techniques may be applied to high-field imaging data to
      uncover novel information about brain-heart interactions. 

PMID- 27044996
TI  - Neuroimaging brainstem circuitry supporting cardiovagal response to pain: a
      combined heart rate variability/ultrahigh-field (7 T) functional magnetic
      resonance imaging study.
AB  - Central autonomic control nuclei in the brainstem have been difficult to evaluate
      non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic
      resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm
      isotropic), to evaluate putative brainstem nuclei that control and/or sense pain
      evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV)
      instantaneously estimated through a point-process approach). The time-variant HF
      HRV signal was used to guide the general linear model analysis of neuroimaging
      data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the
      most prominent reduction evident in the first 2 min. Brainstem nuclei associated
      with pain-evoked HF-HRV reduction were previously implicated in both autonomic
      regulation and pain processing. Specifically, clusters consistent with the
      rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus
      (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus
      rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition
      to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the
      solitary tract and locus coeruleus. Combining high spatial resolution fMRI and
      high temporal resolution HF-HRV allowed for a non-invasive characterization of
      brainstem nuclei, suggesting that nociceptive afference induces pain-processing
      brainstem nuclei to function in concert with known premotor autonomic nuclei in
      order to affect the cardiovagal response to pain. 

PMID- 27044997
TI  - Sensitivity of the resting-state haemodynamic response function estimation to
      autonomic nervous system fluctuations.
AB  - The haemodynamic response function (HRF) is a key component of the blood oxygen
      level-dependent (BOLD) signal, providing the mapping between neural activity and
      the signal measured with functional magnetic resonance imaging (fMRI). Most of
      the time the HRF is associated with task-based fMRI protocols, in which its onset
      is explicitly included in the design matrix. On the other hand, the HRF also
      mediates the relationship between spontaneous neural activity and the BOLD signal
      in resting-state protocols, in which no explicit stimulus is taken into account.
      It has been shown that resting-state brain dynamics can be characterized by
      looking at sparse BOLD 'events', which can be retrieved by point process
      analysis. These events can be then used to retrieve the HRF at rest. Crucially,
      cardiac activity can also induce changes in the BOLD signal, thus affecting both
      the number of these events and the estimation of the haemodynamic response. In
      this study, we compare the resting-state haemodynamic response retrieved by means
      of a point process analysis, taking the cardiac fluctuations into account. We
      find that the resting-state HRF estimation is significantly modulated in the
      brainstem and surrounding cortical areas. From the analysis of two high-quality
      datasets with different temporal and spatial resolution, and through the
      investigation of intersubject correlation, we suggest that spontaneous point
      process response durations are associated with the mean interbeat interval and
      low-frequency power of heart rate variability in the brainstem. 

PMID- 27044998
TI  - Brain-heart interactions: physiology and clinical implications.
AB  - The brain controls the heart directly through the sympathetic and parasympathetic
      branches of the autonomic nervous system, which consists of multi-synaptic
      pathways from myocardial cells back to peripheral ganglionic neurons and further
      to central preganglionic and premotor neurons. Cardiac function can be profoundly
      altered by the reflex activation of cardiac autonomic nerves in response to
      inputs from baro-, chemo-, nasopharyngeal and other receptors as well as by
      central autonomic commands, including those associated with stress, physical
      activity, arousal and sleep. In the clinical setting, slowly progressive
      autonomic failure frequently results from neurodegenerative disorders, whereas
      autonomic hyperactivity may result from vascular, inflammatory or traumatic
      lesions of the autonomic nervous system, adverse effects of drugs and chronic
      neurological disorders. Both acute and chronic manifestations of an imbalanced
      brain-heart interaction have a negative impact on health. Simple, widely
      available and reliable cardiovascular markers of the sympathetic tone and of the
      sympathetic-parasympathetic balance are lacking. A deeper understanding of the
      connections between autonomic cardiac control and brain dynamics through advanced
      signal and neuroimage processing may lead to invaluable tools for the early
      detection and treatment of pathological changes in the brain-heart interaction. 

PMID- 27044999
TI  - The heart side of brain neuromodulation.
AB  - Neuromodulation refers to invasive, minimally invasive or non-invasive techniques
      to stimulate discrete cortical or subcortical brain regions with therapeutic
      purposes in otherwise intractable patients: for example, thousands of advanced
      Parkinsonian patients, as well as patients with tremor or dystonia, benefited by
      deep brain stimulation (DBS) procedures (neural targets: basal ganglia nuclei). A
      new era for DBS is currently opening for patients with drug-resistant depression,
      obsessive-compulsive disorders, severe epilepsy, migraine and chronic pain
      (neural targets: basal ganglia and other subcortical nuclei or associative
      fibres). Vagal nerve stimulation (VNS) has shown clinical benefits in patients
      with pharmacoresistant epilepsy and depression. Non-invasive brain stimulation
      neuromodulatory techniques such as repetitive transcranial magnetic stimulation
      (rTMS) and transcranial direct current stimulation (tDCS) are also being
      increasingly investigated for their therapeutic potential in several neurological
      and psychiatric disorders. In this review, we first address the most common
      neural targets of each of the mentioned brain stimulation techniques, and the
      known mechanisms of their neuromodulatory action on stimulated brain networks.
      Then, we discuss how DBS, VNS, rTMS and tDCS could impact on the function of
      brainstem centres controlling vital functions, critically reviewing their acute
      and long-term effects on brain sympathetic outflow controlling heart function and
      blood pressure. Finally, as there is clear experimental evidence in animals that
      brain stimulation can affect autonomic and heart functions, we will try to give a
      critical perspective on how it may enhance our understanding of the
      cortical/subcortical mechanisms of autonomic cardiovascular regulation, and also
      if it might find a place among therapeutic opportunities in patients with
      otherwise intractable autonomic dysfunctions. 

PMID- 27045000
TI  - Alterations in the coupling functions between cortical and cardio-respiratory
      oscillations due to anaesthesia with propofol and sevoflurane.
AB  - The precise mechanisms underlying general anaesthesia pose important and still
      open questions. To address them, we have studied anaesthesia induced by the
      widely used (intravenous) propofol and (inhalational) sevoflurane anaesthetics,
      computing cross-frequency coupling functions between neuronal, cardiac and
      respiratory oscillations in order to determine their mutual interactions. The
      phase domain coupling function reveals the form of the function defining the
      mechanism of an interaction, as well as its coupling strength. Using a method
      based on dynamical Bayesian inference, we have thus identified and analysed the
      coupling functions for six relationships. By quantitative assessment of the forms
      and strengths of the couplings, we have revealed how these relationships are
      altered by anaesthesia, also showing that some of them are differently affected
      by propofol and sevoflurane. These findings, together with the novel coupling
      function analysis, offer a new direction in the assessment of general anaesthesia
      and neurophysiological interactions, in general. 

PMID- 27045001
TI  - The cost of post-abortion care in developing countries: a comparative analysis of
      four studies.
AB  - Over the last five years, comprehensive national surveys of the cost of post
      abortion care (PAC) to national health systems have been undertaken in Ethiopia,
      Uganda, Rwanda and Colombia using a specially developed costing methodology-the
      Post-abortion Care Costing Methodology (PACCM). The objective of this study is to
      expand the research findings of these four studies, making use of their extensive
      datasets. These studies offer the most complete and consistent estimates of the
      cost of PAC to date, and comparing their findings not only provides generalizable
      implications for health policies and programs, but also allows an assessment of
      the PACCM methodology. We find that the labor cost component varies widely: in
      Ethiopia and Colombia doctors spend about 30-60% more time with PAC patients than
      do nurses; in Uganda and Rwanda an opposite pattern is found. Labor costs range
      from I$42.80 in Uganda to I$301.30 in Colombia. The cost of drugs and supplies
      does not vary greatly, ranging from I$79 in Colombia to I$115 in Rwanda. Capital
      and overhead costs are substantial amounting to 52-68% of total PAC costs. Total
      costs per PAC case vary from I$334 in Rwanda to I$972 in Colombia. The financial
      burden of PAC is considerable: the expense of treating each PAC case is
      equivalent to around 35% of annual per capita income in Uganda, 29% in Rwanda and
      11% in Colombia. Providing modern methods of contraception to women with an unmet
      need would cost just a fraction of the average expenditure on PAC: one year of
      modern contraceptive services and supplies cost only 3-12% of the average cost of
      treating a PAC patient. 

PMID- 27045002
TI  - Expanding HIV testing and counselling into communities: Feasibility,
      acceptability, and effects of an integrated family planning/HTC service delivery
      model by Village Health Teams in Uganda.
AB  - Improving HIV testing and counselling (HTC) requires a range of strategies. This
      article reports on HTC service delivery by Village Health Teams (VHTs) in Uganda
      in the context of a model integrating this new component into pre-existing family
      planning services. Eight health centres from matched pairs were randomly
      allocated to intervention or control. After being trained, 36 VHTs reporting to
      selected facilities in the intervention group started offering HTC along with
      family planning, while VHTs in the control group provided family planning only.
      Proficiency testing was conducted as external quality assurance. A survey of all
      36 VHTs and 137 family planning clients in the intervention group and 119 clients
      in the control group and a review of record data were conducted after 10 months.
      Survey responses by VHTs and their clients in the intervention group demonstrate
      knowledge of counselling messages and safe testing. External quality assessment
      results provide additional evidence of competency. Eighty per cent of the family
      planning clients surveyed in the intervention group received an HIV test during
      the intervention; 27% of those were first-time testers. More clients had ever
      tested for HIV in the intervention group compared with the control; clients also
      retested more often. Findings indicate that this model is feasible and acceptable
      for expanding quality HTC into communities. This study was registered with
      ClinicalTrials.gov, number [NCT02244398]. 

PMID- 27045003
TI  - Prevalence of nonalcoholic fatty liver disease in the middle eastern area: What
      is the exact estimation?

PMID- 27045004
TI  - In-solution patterning of standing up porphyrin based nanostructures within
      hydrogen bonded porous networks--a structural effect of a host matrix on guest
      entities.
AB  - Through an all-solution process, we elaborate a host-guest system based on the
      self-assembly of a porphyrin derivative entrapped in a PTCDI-melamine porous
      network on Au(111). In contrast to the unpatterned molecular assembly,
      complementary STM and surface IR spectroscopy show that the host template
      modifies the packing and the tilt angle of porphyrin nanodomains. 

PMID- 27045005
TI  - Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the
      Inflammatory Response and Infarct Size in Acute Myocardial Infarction.
AB  - BACKGROUND: An excessive inflammatory response after myocardial infarction (MI)
      increases myocardial injury. The toll-like receptor (TLR)-4 is activated by the
      recognition of endogenous ligands and is proinflammatory when there is myocardial
      tissue injury. The apoptosis inhibitor of the macrophage (AIM) is known to
      provoke an efflux of saturated free fatty acids (FFA) due to lipolysis, which
      causes inflammation via the TLR-4 pathway. Therefore, this study investigated the
      hypothesis that AIM causes a proinflammatory response after MI. METHODS AND
      RESULTS: The left anterior descending coronary artery was ligated to induce MI in
      both AIM-knockout (AIM(-/-)) and wild-type (WT) mice. After 3 days, the
      inflammatory response from activation of the TLR-4/NFkappaB pathway was assessed,
      and infarct size was measured by staining with triphenyltetrazolium chloride. In
      addition, left ventricular remodeling was examined after 28 days. Although the
      area at risk was similar between AIM(-/-) and WT mice, the infarct size was
      significantly smaller in AIM(-/-) mice (P=0.02). The heart weight-to-body weight
      ratio and myocardial fibrosis were also decreased in the AIM(-/-) mice, and the
      28-day survival rate was improved (P<0.01). With the reduction of plasma FFA in
      AIM(-/-) mice, myocardial IRAK4 and NFkappaB activity were decreased (all
      P<0.05). Moreover, there was a reduction in myeloperoxidase activity and
      inducible nitric oxide synthase as part of the inflammatory response (P<0.01,
      P=0.03, respectively). Furthermore, NFkappaB DNA-binding activation via TLR-4,
      neutrophil infiltration, and inflammatory mediators were decreased in AIM(-/-)
      mice. CONCLUSIONS: The deletion of AIM reduced the inflammatory response and
      infarct size and improved survival after myocardial infarction.

PMID- 27045006
TI  - Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of
      myeloid derived suppressor cells in cancer.
AB  - Tumor-stroma interactions contribute to tumorigenesis. Tumor cells can educate
      the stroma at primary and distant sites to facilitate the recruitment of
      heterogeneous populations of immature myeloid cells, known as myeloid-derived
      suppressor cells (MDSCs). MDSCs suppress T cell responses and promote tumor
      proliferation. One outstanding question is how the local and distant stroma
      modulate MDSCs during tumor progression. Down-regulation of beta-catenin is
      critical for MDSC accumulation and immune suppressive functions in mice and
      humans. Here, we demonstrate that stroma-derived Dickkopf-1 (Dkk1) targets beta
      catenin in MDSCs, thus exerting immune suppressive effects during tumor
      progression. Mice bearing extraskeletal tumors show significantly elevated levels
      of Dkk1 in bone microenvironment relative to tumor site. Strikingly, Dkk1
      neutralization decreases tumor growth and MDSC numbers by rescuing beta-catenin
      in these cells and restores T cell recruitment at the tumor site. Recombinant
      Dkk1 suppresses beta-catenin target genes in MDSCs from mice and humans and anti
      Dkk1 loses its antitumor effects in mice lacking beta-catenin in myeloid cells or
      after depletion of MDSCs, demonstrating that Dkk1 directly targets MDSCs.
      Furthermore, we find a correlation between CD15(+) myeloid cells and Dkk1 in
      pancreatic cancer patients. We establish a novel immunomodulatory role for Dkk1
      in regulating tumor-induced immune suppression via targeting beta-catenin in
      MDSCs.

PMID- 27045007
TI  - Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct
      hierarchies of HLA class I recognition.
AB  - Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA
      I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism
      impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were
      screened for reactivity against a panel of HLA-I molecules. This revealed
      different and distinct hierarchies of specificity for each KIR3DL1 allotype, with
      KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were
      further reflected in functional studies using NK clones expressing these specific
      KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did
      not categorically define strong/weak KIR3DL1 recognition. Although the
      KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1-HLA-I
      interface, the structures of these three KIR3DL1-HLA-I complexes showed that the
      broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005
      interdomain positioning and increased mobility within its ligand-binding site.
      Collectively, we provide a generic framework for understanding the impact of
      KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.

PMID- 27045008
TI  - NAIP proteins are required for cytosolic detection of specific bacterial ligands
      in vivo.
AB  - NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing
      proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR
      family, apoptosis inhibitory proteins) are NLRs that appear to function as
      cytosolic immunoreceptors for specific bacterial proteins, including flagellin
      and the inner rod and needle proteins of bacterial type III secretion systems
      (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific
      detection of bacterial ligands, genetic evidence has been lacking. Here we report
      the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as
      Naip1-6(Delta/Delta) mice lacking all functional Naip genes. By challenging
      Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we
      demonstrate that Naip1 is uniquely required to detect T3SS needle protein and
      Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1
      nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-)
      mice retain some residual responsiveness to flagellin in vivo, whereas Naip1
      6(Delta/Delta) mice fail to respond to cytosolic flagellin, consistent with
      previous biochemical data implicating NAIP6 in flagellin detection. Our results
      provide genetic evidence that specific NAIP proteins function to detect specific
      bacterial proteins in vivo.

PMID- 27045009
TI  - Synthesis, regioselective aerobic Pd(ii)-catalyzed C-H bond alkenylation and the
      photophysical properties of pyrenylphenylpyrazoles.
AB  - This paper reports the synthesis, regioselective aerobic Pd(ii)-catalyzed C-H
      bond alkenylation and the photophysical properties of pyrenylphenylpyrazoles. 

PMID- 27045011
TI  - Healthcare needs of adolescents with congenital heart disease transitioning into
      adulthood: a Delphi survey of patients, parents, and healthcare providers.
AB  - BACKGROUND: The increasing survival of children with congenital heart disease
      (CHD) challenges healthcare systems regarding how to manage the many health needs
      of patients undergoing transitional care. A comprehensive understanding of the
      perspectives of patients, parents, and healthcare providers is required.
      OBJECTIVE: This study systematically identified the healthcare needs of
      adolescents with CHD transitioning into young adults by collecting the
      perspectives of patients, parents, and healthcare providers. METHODS: A sample of
      CHD patients ( n = 29), parents of children with CHD ( n = 29), and healthcare
      providers ( n = 16) completed the two-round Delphi study, and 64 healthcare needs
      were identified. The central tendency and the level of dispersion were computed
      in order to establish a consensus. RESULTS: A consensus was reached on 25
      healthcare needs including health, family, individual, interpersonal interaction,
      and policy dimensions, which were classified as important with a moderate to high
      level of agreement by all three groups. The three groups were strongly agreed
      that "encouraging the patient to learn health self-management" and "cultivating a
      positive attitude toward the illness" were very important. The opinions of the
      three groups differed significantly on 12 needs ( p < 0.05) related to health,
      family, and policy dimensions. CONCLUSION: A consensus was reached on the needs
      that were identified as being potentially valid measures of the healthcare needs
      of adolescents with CHD transitioning into young adults. The identified needs can
      serve as the basis for establishing a transitional health passport and developing
      a clinical intervention for adolescents with CHD transitioning into young adults.

PMID- 27045012
TI  - Detection of Volatile Organic Compounds by Self-assembled Monolayer Coated Sensor
      Array with Concentration-independent Fingerprints.
AB  - In this paper, we have modeled and analyzed affinities and kinetics of volatile
      organic compounds (VOCs) adsorption (and desorption) on various surface chemical
      groups using multiple self-assembled monolayers (SAMs) functionalized film bulk
      acoustic resonator (FBAR) array. The high-frequency and micro-scale resonator
      provides improved sensitivity in the detections of VOCs at trace levels. With the
      study of affinities and kinetics, three concentration-independent intrinsic
      parameters (monolayer adsorption capacity, adsorption energy constant and
      desorption rate) of gas-surface interactions are obtained to contribute to a
      multi-parameter fingerprint library of VOC analytes. Effects of functional
      group's properties on gas-surface interactions are also discussed. The proposed
      sensor array with concentration-independent fingerprint library shows potential
      as a portable electronic nose (e-nose) system for VOCs discrimination and gas
      sensitive materials selections. 

PMID- 27045016
TI  - Molecular Mechanism of Mutant CALR-Mediated Transformation.
AB  - Elf and colleagues used an elegant series of functional and biochemical assays to
      investigate the molecular mechanism of mutant calreticulin (CALR)-driven cellular
      transformation in myeloproliferative neoplasms (MPN). Mutant CALR is sufficient
      to induce MPN in mouse transplantation experiments, and transformation is
      dependent upon physical interaction mediated by the positive electrostatic charge
      of the mutant CALR C-terminal domain and the thrombopoietin receptor MPL.

PMID- 27045017
TI  - STAT5 Loss Awakens the Dark Force in Natural Killer Cells.
AB  - Natural killer cells (NK) are commonly considered to be potent antitumor effector
      cells. The study by Gotthardt and colleagues challenges this concept and reveals
      that STAT5-deficient/inhibited NK cells induce angiogenesis and promote tumor
      progression. These unexpected findings shed new light on potential adverse
      effects of JAK-STAT inhibitors in the clinics.

PMID- 27045019
TI  - Correction: Using Quantitative Seroproteomics to Identify Antibody Biomarkers in
      Pancreatic Cancer.

PMID- 27045018
TI  - Lifting Up the HAT: Synthetic Lethal Screening Reveals a Novel Vulnerability at
      the CBP-p300 Axis.
AB  - Cancer genotype-specific synthetic lethal vulnerabilities represent promising
      therapeutic targets. In this issue of Cancer Discovery, Ogiwara and colleagues
      uncover a synthetic lethal relationship between two histone acetyl transferase
      paralogs, CBP and p300, highlighting that cancer cells deficient in CBP are
      uniquely sensitized to genetic and chemical inhibition of p300.

PMID- 27045020
TI  - Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell
      Immunity to Exert an Anticancer Phenotype.
AB  - Macroenvironmental factors, including a patient's physical and social
      environment, play a role in cancer risk and progression. Our previous studies
      show that living in an enriched environment (EE) providing complex stimuli
      confers an anticancer phenotype in mice mediated, in part by a specific
      neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key
      brain mediator. Here, we investigated how an EE modulated T-cell immunity and its
      role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells
      were required to mediate the anticancer effects of an EE in an orthotropic model
      of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in
      the phenotype of T-cell populations, characterized by a decrease in the ratio of
      CD4 T helper to CD8 cytotoxic T lymphocytes (CTL). Overexpression of hypothalamic
      BDNF reproduced EE-induced T-cell phenotypes in SLT, whereas knockdown of
      hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol
      and mifepristone blocked the EE-associated modulation of CTLs in SLT, suggesting
      that both the sympathetic nervous system and the hypothalamic-pituitary-adrenal
      axis were involved. Our results demonstrated that enhanced anticancer effect of
      an EE was mediated at least in part through modulation of T-cell immunity and
      provided support to the emerging concept of manipulating a single gene in the
      brain to improve cancer immunotherapy. Cancer Immunol Res; 4(6); 488-97. (c)2016
      AACR.

PMID- 27045021
TI  - Antibody-Mediated Phosphatidylserine Blockade Enhances the Antitumor Responses to
      CTLA-4 and PD-1 Antibodies in Melanoma.
AB  - In tumor-bearing animals, the membrane phospholipid phosphatidylserine (PS)
      suppresses immune responses, suggesting that PS signaling could counteract the
      antitumor effect of antibody-driven immune checkpoint blockade. Here, we show
      that treating melanoma-bearing mice with a PS-targeting antibody enhances the
      antitumor activity of downstream checkpoint inhibition. Combining PS-targeting
      antibodies with CTLA-4 or PD-1 blockade resulted in significantly greater
      inhibition of tumor growth than did single-agent therapy. Moreover, combination
      therapy enhanced CD4(+) and CD8(+) tumor-infiltrating lymphocyte numbers;
      elevated the fraction of cells expressing the proinflammatory cytokines IL2,
      IFNgamma, and TNFalpha; and increased the ratio of CD8 T cells to myeloid-derived
      suppressor cells and regulatory T cells in tumors. Similar changes in immune cell
      profiles were observed in splenocytes. Taken together, these data show that
      antibody-mediated PS blockade enhances the antitumor efficacy of immune
      checkpoint inhibition. Cancer Immunol Res; 4(6); 531-40. (c)2016 AACR.

PMID- 27045022
TI  - Altered Expression and Splicing of ESRP1 in Malignant Melanoma Correlates with
      Epithelial-Mesenchymal Status and Tumor-Associated Immune Cytolytic Activity.
AB  - Melanoma is one of the major cancer types for which new immune-based cancer
      treatments have achieved promising results. However, anti-PD-1 and anti-CTLA-4
      therapies are effective only in some patients. Hence, predictive molecular
      markers for the development of clinical strategies targeting immune checkpoints
      are needed. Using The Cancer Genome Atlas (TCGA) RNAseq data, we found that
      expression of ESRP1, encoding a master splicing regulator in the epithelial
      mesenchymal transition (EMT), was inversely correlated with tumor-associated
      immune cytolytic activity. That association holds up across multiple TCGA tumor
      types, suggesting a link between tumor EMT status and infiltrating lymphocyte
      activity. In melanoma, ESRP1 mainly exists in a melanocyte-specific truncated
      form transcribed from exon 13. This was validated by analyzing CCLE cell line
      data, public CAGE data, and RT-PCR in primary cultured melanoma cell lines. Based
      on ESRP1 expression, we divided TCGA melanoma cases into ESRP1-low, -truncated,
      and -full-length groups. ESRP1-truncated tumors comprise approximately two thirds
      of melanoma samples and reside in an apparent transitional state between
      epithelial and mesenchymal phenotypes. ESRP1 full-length tumors express
      epithelial markers and constitute about 5% of melanoma samples. In contrast,
      ESRP1-low tumors express mesenchymal markers and are high in immune cytolytic
      activity as well as PD-L2 and CTLA-4 expression. Those tumors are associated with
      better patient survival. Results from our study suggest a path toward the use of
      ESRP1 and other EMT markers as informative biomarkers for immunotherapy. Cancer
      Immunol Res; 4(6); 552-61. (c)2016 AACR.

PMID- 27045023
TI  - Augmentation of CAR T-cell Trafficking and Antitumor Efficacy by Blocking Protein
      Kinase A Localization.
AB  - Antitumor treatments based on the infusion of T cells expressing chimeric antigen
      receptors (CAR T cells) are still relatively ineffective for solid tumors, due to
      the presence of immunosuppressive mediators [such as prostaglandin E2 (PGE2) and
      adenosine] and poor T-cell trafficking. PGE2 and adenosine activate protein
      kinase A (PKA), which then inhibits T-cell receptor (TCR) activation. This
      inhibition process requires PKA to localize to the immune synapse via binding to
      the membrane protein ezrin. We generated CAR T cells that expressed a small
      peptide called the "regulatory subunit I anchoring disruptor" (RIAD) that
      inhibits the association of PKA with ezrin, thus blunting the negative effects of
      PKA on TCR activation. After exposure to PGE2 or adenosine in vitro, CAR-RIAD T
      cells showed increased TCR signaling, released more cytokines, and showed
      enhanced killing of tumor cells compared with CAR T cells. When injected into
      tumor-bearing mice, the antitumor efficacy of murine and human CAR-RIAD T cells
      was enhanced compared with that of CAR T cells, due to resistance to tumor
      induced hypofunction and increased T-cell infiltration of established tumors.
      Subsequent in vitro assays showed that both mouse and human CAR-RIAD cells
      migrated more efficiently than CAR cells did in response to the chemokine CXCL10
      and also had better adhesion to various matrices. Thus, the intracellular
      addition of the RIAD peptide to adoptively transferred CAR T cells augments their
      efficacy by increasing their effector function and by improving trafficking into
      tumor sites. This treatment strategy, therefore, shows potential clinical
      application for treating solid tumors. Cancer Immunol Res; 4(6); 541-51. (c)2016
      AACR.

PMID- 27045024
TI  - Longitudinal Patterns of Change in Systolic Blood Pressure and Incidence of
      Cardiovascular Disease: The Atherosclerosis Risk in Communities Study.
AB  - Elevated blood pressure in midlife contributes significantly to the risk of
      cardiovascular disease. However, patterns of blood pressure increase may differ
      among individuals and may result in differential risk. Our goal was to examine
      the contribution of longitudinal patterns of blood pressure change to incidence
      of heart failure, coronary heart disease, stroke, and cardiovascular disease
      mortality. Latent class growth models were used to identify patterns of change in
      blood pressure across 4 clinical examinations (1987-1998) among 9845
      Atherosclerosis Risk in Communities (ARIC) cohort participants (mean age, 53.7
      [SD 5.7] years). Patterns of change in systolic blood pressure included slowly
      and steeply increasing, a decreasing and a sustained elevated blood pressure.
      Changes in diastolic and mid-blood pressure (1/2 systolic+1/2 diastolic) were
      less pronounced. The association of blood pressure pattern group membership with
      incidence of clinical outcomes was examined in follow-up from the fourth clinical
      examination (1996-1998) to December 31, 2011, using Poisson regression models
      adjusted for demographic and metabolic characteristics, and hypertension
      medication use. A gradient of rates of all events was observed across the
      identified patterns. Associations were attenuated after adjustment for
      covariates. Cumulative systolic blood pressure load, rather than the temporal
      pattern of change in systolic blood pressure itself, plays a role in determining
      the risk of cardiovascular disease, in particular, of heart failure and
      cardiovascular disease mortality, independent of blood pressure level measured at
      one point in time.

PMID- 27045025
TI  - The Promiscuous Mineralocorticoid Receptor.

PMID- 27045026
TI  - Cardiovascular Regulation by the Arcuate Nucleus of the Hypothalamus:
      Neurocircuitry and Signaling Systems.

PMID- 27045027
TI  - Gastrorenal Axis.

PMID- 27045028
TI  - Role of Bile Acid-Regulated Nuclear Receptor FXR and G Protein-Coupled Receptor
      TGR5 in Regulation of Cardiorenal Syndrome (Cardiovascular Disease and Chronic
      Kidney Disease).

PMID- 27045029
TI  - Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require
      Functional Angiotensin Type 1a Receptors.
AB  - We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular
      injury induced by aldosterone activation of mineralocorticoid receptors in
      Agtr1a(-/-) and wild-type (WT) mice infused with aldosterone for 14 days while
      receiving 1% NaCl in drinking water. Aldosterone increased systolic blood
      pressure (BP) by ~30 mm Hg in WT mice and ~50 mm Hg in Agtr1a(-/-) mice.
      Aldosterone induced aortic and small artery remodeling, impaired endothelium
      dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition
      and vascular inflammation. None of these vascular effects were observed in
      Agtr1a(-/-) mice. Aldosterone effects were prevented by the AGTR1 antagonist
      losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP
      increase and mesenteric artery remodeling in WT and Agtr1a(-/-) mice. Agtr1a(-/-)
      mice infused with aldosterone did not increase sodium excretion in response to a
      sodium chloride challenge, suggesting that sodium retention could contribute to
      the exaggerated BP rise induced by aldosterone. Agtr1a(-/-) mice had decreased
      mesenteric artery expression of the calcium-activated potassium channel Kcnmb1,
      which may enhance myogenic tone and together with sodium retention, exacerbate BP
      responses to aldosterone/salt in Agtr1a(-/-) mice. We conclude that although
      aldosterone activation of mineralocorticoid receptors raises BP more in Agtr1a(-/
      ) mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce
      vascular remodeling and inflammation and endothelial dysfunction.

PMID- 27045030
TI  - Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Pathological
      Cardiac Hypertrophy.
AB  - Dysregulation of the ubiquitin proteasome system components ubiquitin ligases and
      proteasome plays an important role in the pathogenesis of cardiac hypertrophy.
      However, little is known about the role of another ubiquitin proteasome system
      component, the deubiquitinating enzymes, in cardiac hypertrophy. Here, we
      revealed a crucial role of ubiquitin specific protease 4 (USP4), a
      deubiquitinating enzyme prominently expressed in the heart, in attenuating
      pathological cardiac hypertrophy and dysfunction. USP4 levels were consistently
      decreased in human failing hearts and in murine hypertrophied hearts. Adenovirus
      mediated gain- and loss-of-function approaches indicated that deficiency of
      endogenous USP4 promoted myocyte hypertrophy induced by angiotensin II in vitro,
      whereas restoration of USP4 significantly attenuated the prohypertrophic effect
      of angiotensin II. To corroborate the role of USP4 in vivo, we generated USP4
      global knockout mice and mice with cardiac-specific overexpression of USP4.
      Consistent with the in vitro study, USP4 depletion exacerbated the hypertrophic
      phenotype and cardiac dysfunction in mice subjected to pressure overload, whereas
      USP4 transgenic mice presented ameliorated pathological cardiac hypertrophy
      compared with their control littermates. Molecular analysis revealed that USP4
      deficiency augmented the activation of the transforming growth factor beta
      activated kinase 1 (TAK1)-(JNK1/2)/P38 signaling in response to hypertrophic
      stress, and blockage of TAK1 activation abolished the pathological effects of
      USP4 deficiency in vivo. These findings provide the first evidence for the
      involvement of USP4 in cardiac hypertrophy, and shed light on the therapeutic
      potential of targeting USP4 in the treatment of cardiac hypertrophy.

PMID- 27045031
TI  - Peroxisome Proliferator-Activated Receptor gamma Level Contributes to Structural
      Integrity and Component Production of Elastic Fibers in the Aorta.
AB  - Loss of integrity and massive disruption of elastic fibers are key features of
      abdominal aortic aneurysm (AAA). Peroxisome proliferator-activated receptor gamma
      (PPARgamma) has been shown to attenuate AAA through inhibition of inflammation
      and proteolytic degradation. However, its involvement in elastogenesis during AAA
      remains unclear. PPARgamma was highly expressed in human AAA within all vascular
      cells, including inflammatory cells and fibroblasts. In the aortas of transgenic
      mice expressing PPARgamma at 25% normal levels (Pparg(C) (/-) mice), we observed
      the fragmentation of elastic fibers and reduced expression of vital elastic fiber
      components of elastin and fibulin-5. These were not observed in mice with 50%
      normal PPARgamma expression (Pparg(+/-) mice). Infusion of a moderate dose of
      angiotensin II (500 ng/kg per minute) did not induce AAA but Pparg(+/-) aorta
      developed flattened elastic lamellae, whereas Pparg(C/-) aorta showed severe
      destruction of elastic fibers. After infusion of angiotensin II at 1000 ng/kg per
      minute, 73% of Pparg(C/-) mice developed atypical suprarenal aortic aneurysms:
      superior mesenteric arteries were dilated with extensive collagen deposition in
      adventitia and infiltrations of inflammatory cells. Although matrix
      metalloproteinase inhibition by doxycycline somewhat attenuated the dilation of
      aneurysm, it did not reduce the incidence nor elastic lamella deterioration in
      angiotensin II-infused Pparg(C/-) mice. Furthermore, PPARgamma antagonism
      downregulated elastin and fibulin-5 in fibroblasts, but not in vascular smooth
      muscle cells. Chromatin immunoprecipitation assay demonstrated PPARgamma binding
      in the genomic sequence of fibulin-5 in fibroblasts. Our results underscore the
      importance of PPARgamma in AAA development though orchestrating proper
      elastogenesis and preserving elastic fiber integrity.

PMID- 27045032
TI  - Development and Characterization of an Inducible Rat Model of Chronic
      Thromboembolic Pulmonary Hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not
      only limits patients quality of life but also causes significant morbidity and
      mortality. The treatment of choice is pulmonary endarterectomy. However numerous
      patients do not qualify for pulmonary endarterectomy or present with residual
      vasculopathy post pulmonary endarterectomy and require specific vasodilator
      treatment. Currently, there is no available specific small animal model of CTEPH
      that could serve as tool to identify targetable molecular pathways and to test
      new treatment options. Thus, we generated and standardized a rat model that not
      only resembles functional and histological features of CTEPH but also emulates
      thrombi fibrosis. The pulmonary embolism protocol consisted of 3 sequential tail
      vein injections of fibrinogen/collagen-covered polystyrene microspheres combined
      with thrombin and administered to 10-week-old male Wistar rats. After the third
      embolism, rats developed characteristic features of CTEPH including elevated
      right ventricular systolic pressure, right ventricular cardiomyocyte hypertrophy,
      pulmonary artery remodeling, increased serum brain natriuretic peptide levels,
      thrombi fibrosis, and formation of pulmonary cellular-fibrotic lesions. The
      current animal model seems suitable for detailed study of CTEPH pathophysiology
      and permits preclinical testing of new pharmacological therapies against CTEPH. 

PMID- 27045033
TI  - Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor
      Prognosis for Oral Squamous Cell Carcinoma Patients.
AB  - Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) plays a role in the
      development and progression of epithelial malignancies. Measurements of urinary
      PGE-M, a stable metabolite of PGE2, reflect systemic PGE2 levels. Here, we
      investigated whether urinary PGE-M levels were elevated in healthy tobacco users
      and in patients with oral squamous cell carcinoma (OSCC). Median urinary PGE-M
      levels were increased in healthy tobacco quid chewers [21.3 ng/mg creatinine
      (Cr); n = 33; P = 0.03] and smokers (32.1 ng/mg Cr; n = 31; P < 0.001) compared
      with never tobacco quid chewers-never smokers (18.8 ng/mg Cr; n = 30). Urinary
      PGE-M levels were also compared in OSCC patients versus healthy tobacco users. An
      approximately 1-fold increase in median urinary PGE-M level was found in OSCC
      patients (48.7 ng/mg Cr, n = 78) versus healthy controls (24.5 ng/mg Cr, n = 64;
      P < 0.001). We further determined whether baseline urinary PGE-M levels were
      prognostic in OSCC patients who underwent treatment with curative intent. A
      nearly 1-fold increase in baseline urinary PGE-M levels (64.7 vs. 33.8 ng/mg Cr,
      P < 0.001) was found in the group of OSCC patients who progressed (n = 37)
      compared with the group that remained progression free (n = 41). Patients with
      high baseline levels of urinary PGE-M had both worse disease-specific survival
      [HR, 1.01 per unit increase; 95% confidence interval (CI), 1.01-1.02; P < 0.001]
      and overall survival (HR, 1.01 per unit increase; 95% CI, 1.00-1.02; P = 0.03).
      Taken together, our findings raise the possibility that NSAIDs, prototypic
      inhibitors of PGE2 synthesis, may be beneficial for reducing the risk of tobacco
      related aerodigestive malignancies or treating OSCC patients with high urinary
      PGE-M levels. Cancer Prev Res; 9(6); 428-36. (c)2016 AACR.

PMID- 27045034
TI  - Prognostic Significance of VEGF after Twenty-Year Follow-up in a Randomized Trial
      of Fenretinide in Non-Muscle-Invasive Bladder Cancer.
AB  - Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive
      disease, but no effective preventive treatments are available. In addition, no
      reliable prognostic biomarkers have been identified. We assessed the long-term
      effect of the oral retinoid fenretinide and the prognostic value of circulating
      VEGF levels. We updated through the Tumor Registry the vital status of 99
      patients with resected Ta/T1 bladder tumors who were recruited in a randomized
      trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels
      measured at baseline and 12 months were available in a subgroup of 62 patients.
      After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of
      bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or
      bladder cancer survival (BCS) was affected by fenretinide (log-rank P >= 0.2).
      DNA aneuploidy in bladder washing was associated with shorter OS (P = 0.02), CS
      (P = 0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top
      quintile (>=350 pg/mL) had a significantly shorter OS (P = 0.01), CS (P = 0.02),
      and BCS (P = 0.008). The trend across quintiles of VEGF was significant for BCS
      (P = 0.007). Multivariate analyses showed that, in addition to smoking status,
      VEGF level in the top quintile was an independent prognostic factor for OS (HR =
      2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR = 8.9; 95%
      CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with
      NMIBC. High serum VEGF level was a significant predictor of overall and cancer
      death and may help to identify high-risk subjects who may benefit from a
      preventive therapy. Cancer Prev Res; 9(6); 437-44. (c)2016 AACR.

PMID- 27045035
TI  - Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated
      with Malaria in Pregnancy.
AB  - Plasmodium falciparum infection during pregnancy leads to abortions, stillbirth,
      low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate
      in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein
      exposed on the P. falciparum IE membrane. Plasmodium berghei IE infection in
      pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we
      describe a transgenic P. berghei parasite expressing the full-length var2CSA
      extracellular region (domains DBL1X to DBL6epsilon) fused to a P. berghei
      exported protein (EMAP1) and characterize a var2CSA-based mouse model of PM.
      BALB/c mice were infected at midgestation with different doses of P. berghei
      var2CSA (P. berghei-VAR) or P. berghei wild-type IEs. Infection with 10(4) P.
      berghei-VAR IEs induced a higher incidence of stillbirth and lower fetal weight
      than P. berghei At doses of 10(5) and 10(6) IEs, P. berghei-VAR-infected mice
      showed increased maternal mortality during pregnancy and fetal loss,
      respectively. Parasite loads in infected placentas were similar between parasite
      lines despite differences in maternal outcomes. Fetal weight loss normalized for
      parasitemia was higher in P. berghei-VAR-infected mice than in P. berghei
      infected mice. In vitro assays showed that higher numbers of P. berghei-VAR IEs
      than P. berghei IEs adhered to placental tissue. Immunization of mice with P.
      berghei-VAR elicited IgG antibodies reactive to DBL1-6 recombinant protein,
      indicating that the topology of immunogenic epitopes is maintained between DBL1-6
      EMAP1 on P. berghei-VAR and recombinant DBL1-6 (recDBL1-6). Our data suggested
      that impairments in pregnancy caused by P. berghei-VAR infection were
      attributable to var2CSA expression. This model provides a tool for preclinical
      evaluation of protection against PM induced by approaches that target var2CSA.

PMID- 27045036
TI  - Cellular Microbiology of Mycoplasma canis.
AB  - Mycoplasma canis can infect many mammalian hosts but is best known as a commensal
      or opportunistic pathogen of dogs. The unexpected presence of M. canis in brains
      of dogs with idiopathic meningoencephalitis prompted new in vitro studies to help
      fill the void of basic knowledge about the organism's candidate virulence
      factors, the host responses that it elicits, and its potential roles in
      pathogenesis. Secretion of reactive oxygen species and sialidase varied
      quantitatively (P < 0.01) among strains of M. canis isolated from canine brain
      tissue or mucosal surfaces. All strains colonized the surface of canine MDCK
      epithelial and DH82 histiocyte cells and murine C8-D1A astrocytes. Transit
      through MDCK and DH82 cells was demonstrated by gentamicin protection assays and
      three-dimensional immunofluorescence imaging. Strains further varied (P < 0.01)
      in the extents to which they influenced the secretion of tumor necrosis factor
      alpha (TNF-alpha) and the neuroendocrine regulatory peptide endothelin-1 by DH82
      cells. Inoculation with M. canis also decreased major histocompatibility complex
      class II (MHC-II) antigen expression by DH82 cells (P < 0.01), while secretion of
      gamma interferon (IFN-gamma), interleukin-6 (IL-6), interleukin-10 (IL-10), and
      complement factor H was unaffected. The basis for differences in the responses
      elicited by these strains was not obvious in their genome sequences. No acute
      cytopathic effects on any homogeneous cell line, or consistent patterns of M.
      canis polyvalent antigen distribution in canine meningoencephalitis case brain
      tissues, were apparent. Thus, while it is not likely a primary neuropathogen, M.
      canis has the capacity to influence meningoencephalitis through complex
      interactions within the multicellular and neurochemical in vivo milieu.

PMID- 27045037
TI  - Genetic and Molecular Basis of Kingella kingae Encapsulation.
AB  - Kingella kingae is a common cause of invasive disease in young children and was
      recently found to produce a polysaccharide capsule containing N
      acetylgalactosamine (GalNAc) and beta-3-deoxy-d-manno-octulosonic acid (betaKdo).
      Given the role of capsules as important virulence factors and effective vaccine
      antigens, we set out to determine the genetic determinants of K. kingae
      encapsulation. Using a transposon library and a screen for nonencapsulated
      mutants, we identified the previously identified ctrABCD (ABC transporter)
      operon, a lipA (kpsC)-like gene, a lipB (kpsS)-like gene, and a putative
      glycosyltransferase gene designated csaA (capsule synthesis type a gene A). These
      genes were found to be present at unlinked locations scattered throughout the
      genome, an atypical genetic arrangement for Gram-negative bacteria that elaborate
      a capsule dependent on an ABC-type transporter for surface localization. The csaA
      gene product contains a predicted glycosyltransferase domain with structural
      homology to GalNAc transferases and a predicted capsule synthesis domain with
      structural homology to Kdo transferases, raising the possibility that this enzyme
      is responsible for alternately linking GalNAc to betaKdo and betaKdo to GalNAc.
      Consistent with this conclusion, mutation of the DXD motif in the GalNAc
      transferase domain and of the HP motif in the Kdo transferase domain resulted in
      a loss of encapsulation. Examination of intracellular and surface-associated
      capsule in deletion mutants and complemented strains further implicated the lipA
      (kpsC)-like gene, the lipB (kpsS)-like gene, and the csaA gene in K. kingae
      capsule production. These data define the genetic requirements for encapsulation
      in K. kingae and demonstrate an atypical organization of capsule synthesis,
      assembly, and export genes.

PMID- 27045039
TI  - Cholesterol metabolism: A review of how ageing disrupts the biological mechanisms
      responsible for its regulation.
AB  - Cholesterol plays a vital role in the human body as a precursor of steroid
      hormones and bile acids, in addition to providing structure to cell membranes.
      Whole body cholesterol metabolism is maintained by a highly coordinated balancing
      act between cholesterol ingestion, synthesis, absorption, and excretion. The aim
      of this review is to discuss how ageing interacts with these processes. Firstly,
      we will present an overview of cholesterol metabolism. Following this, we discuss
      how the biological mechanisms which underpin cholesterol metabolism are effected
      by ageing. Included in this discussion are lipoprotein dynamics, cholesterol
      absorption/synthesis and the enterohepatic circulation/synthesis of bile acids.
      Moreover, we discuss the role of oxidative stress in the pathological progression
      of atherosclerosis and also discuss how cholesterol biosynthesis is effected by
      both the mammalian target of rapamycin and sirtuin pathways. Next, we examine how
      diet and alterations to the gut microbiome can be used to mitigate the impact
      ageing has on cholesterol metabolism. We conclude by discussing how mathematical
      models of cholesterol metabolism can be used to identify therapeutic
      interventions. 

PMID- 27045038
TI  - The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated
      Inflammasome Activation.
AB  - Tick saliva contains a number of effector molecules that inhibit host immunity
      and facilitate pathogen transmission. How tick proteins regulate immune
      signaling, however, is incompletely understood. Here, we describe that loop 2 of
      sialostatin L2, an anti-inflammatory tick protein, binds to annexin A2 and
      impairs the formation of the NLRC4 inflammasome during infection with the
      rickettsial agent Anaplasma phagocytophilum Macrophages deficient in annexin A2
      secreted significantly smaller amounts of interleukin-1beta (IL-1beta) and IL-18
      and had a defect in NLRC4 inflammasome oligomerization and caspase-1 activation.
      Accordingly, Annexin a2-deficient mice were more susceptible to A.
      phagocytophilum infection and showed splenomegaly, thrombocytopenia, and
      monocytopenia. Providing translational support to our findings, better binding of
      annexin A2 to sialostatin L2 in sera from 21 out of 23 infected patients than in
      sera from control individuals was also demonstrated. Overall, we establish a
      unique mode of inflammasome evasion by a pathogen, centered on a blood-feeding
      arthropod.

PMID- 27045040
TI  - Identification of Possible Pathways for C-C Bond Formation during Electrochemical
      Reduction of CO2: New Theoretical Insights from an Improved Electrochemical
      Model.
AB  - We have carried out a periodic Kohn-Sham density functional theory investigation
      of the pathways by which carbon-carbon bonds could be formed during the
      electrochemical reduction of CO2 on Cu(100) using a model that includes the
      effects of the electrochemical potential, solvent, and electrolyte. The
      electrochemical potential was set by relating the applied potential to the Fermi
      energy and then calculating the number of electrons required by the simulation
      cell for that specific Fermi energy. The solvent was included as a continuum
      dielectric, and the electrolyte was described using a linearized Poisson
      Boltzmann model. The calculated potential of zero charge for a variety of
      surfaces agrees with experiment to within a mean average error of 0.09 V, thereby
      validating the assumptions of the model. Analysis of the mechanism for C-C bond
      formation revealed that at low-applied potential, C-C bond formation occurs
      through a CO dimer. However, at high applied potentials, a large activation
      barrier blocks this pathway; therefore, C-C bond formation occurs through
      reaction of adsorbed CHO and CO. Rate parameters determined from our calculations
      were used to simulate the kinetics of ethene formation during the electrochemical
      reduction of CO over a Cu(100) surface. An excellent match was observed between
      previously reported measurements of the partial current for ethene formation as a
      function of applied voltage and the variation in the partial current for C-C bond
      formation predicted by our microkinetic model. The electrochemical model reported
      here is simple, fairly easy to implement, and involves only a small increase in
      computational cost over calculations neglecting the effects of the electrolyte
      and the applied field. Therefore, it can be used to study the effects of applied
      potential and electrolyte composition on the energetics of surface reactions for
      a wide variety of electrochemical reactions. 

PMID- 27045041
TI  - Three-dimensional printing titanium ribs for complex reconstruction after
      extensive posterolateral chest wall resection in lung cancer.

PMID- 27045042
TI  - Association of cardiac biomarkers with acute kidney injury after cardiac surgery:
      A multicenter cohort study.
AB  - OBJECTIVE: Acute kidney injury is common after cardiac surgery and associated
      with postoperative mortality. Perioperative cardiac biomarkers may predict acute
      kidney injury and mortality. We evaluated whether cardiac biomarkers were
      associated with severe acute kidney injury, defined as a doubling in serum
      creatinine or requiring renal replacement therapy during hospital stay after
      surgery, and mortality. METHODS: In a prospective multicenter cohort of adults
      undergoing cardiac surgery, we measured the following biomarkers in preoperative
      and postoperative banked plasma: high-sensitivity troponin T, cardiac troponin I,
      creatine kinase-MB, and N-terminal prohormone of brain natriuretic peptide.
      RESULTS: In the patients who were discharged alive, severe acute kidney injury
      occurred in 37 of 960 (3.9%), and 43 of 960 (4.5%) died within 1 year of follow
      up. N-terminal prohormone of brain natriuretic peptide was the only preoperative
      biomarker that was independently associated with severe acute kidney injury (with
      log transformation, adjusted odds ratio, 1.4; 95% confidence interval, 1.0-1.9).
      Biomarkers measured within 6 hours of surgery (day 1) were all associated with
      severe acute kidney injury. Preoperative N-terminal prohormone of brain
      natriuretic peptide was also independently associated with 1-year mortality (with
      log transformation, adjusted odds ratio, 1.7; 95% confidence interval, 1.2-2.2).
      Patients in the highest tertile for N-terminal prohormone of brain natriuretic
      peptide preoperatively (>1006.4 ng/L) had marked increases in their risk for 1
      year mortality (adjusted odds ratio, 27.2; 95% confidence interval, 3.5-213.5).
      Day 1 N-terminal prohormone of brain natriuretic peptide was associated with
      mortality independently of change in serum creatinine from preoperative baseline.
      CONCLUSIONS: Of the studied biomarkers, N-terminal prohormone of brain
      natriuretic peptide was the only preoperative biomarker independently associated
      with severe acute kidney injury and mortality. Early increases in postoperative
      cardiac biomarkers were associated with severe acute kidney injury after cardiac
      surgery. Future research should focus on whether interventions that lower N
      terminal prohormone of brain natriuretic peptide can affect postoperative
      outcomes.

PMID- 27045043
TI  - Early and midterm outcomes of triple patch technique for postinfarction
      ventricular septal defects.
AB  - OBJECTIVE: Early and midterm outcomes were evaluated in patients who had
      postinfarction ventricular septal defect (VSD) and underwent VSD repair using the
      triple patch technique. METHODS: Twenty-one patients underwent VSD repair for
      postinfarction VSD between April 2004 and September 2015. A retrospective
      analysis of all in-hospital and postdischarge data was performed. In addition, we
      compared pre- and perioperative variables between survivors and nonsurvivors.
      RESULTS: Thirty-day mortality was 23.8% (5 patients). Three patients died due to
      low output syndrome and 2 patients died due to sepsis. All of these patients were
      in cardiogenic shock preoperatively. Although 3 patients had a small residual
      shunt after surgery, the residual shunt disappeared 6 months after surgery in 1
      patient and has been decreasing gradually in another. The mean follow-up was 43.5
      +/- 36.1 months. Overall survival rates (Kaplan-Meier method) at 3 and 8 years
      were 70.8% and 57.9%, respectively. Compared with survivors, nonsurvivors had a
      higher incidence of preoperative cardiogenic shock, higher incidence of chronic
      kidney disease and end-organ failure, and longer aortic crossclamp times during
      surgery. CONCLUSIONS: Early and midterm outcomes of modified infarct exclusion
      using the triple patch technique are acceptable. This technique is safe and
      simple, and may be useful for reducing postoperative residual shunt.

PMID- 27045044
TI  - The impact of concomitant pulmonary hypertension on early and late outcomes
      following surgery for mitral stenosis.
AB  - OBJECTIVES: To provide initial evidence on the management of mitral stenosis and
      pulmonary hypertension (PH) based on short-term and long-term outcomes following
      mitral valve surgery. METHODS: Consecutive patients with mitral stenosis (n =
      317) who had undergone mitral valve surgery between 1992 and 2014 with recorded
      pulmonary artery pressure (PAP) data were reviewed. PH severity, based on
      systolic PAP, was categorized as mild (35 to 44 mm Hg), moderate (45 to 59 mm
      Hg), or severe (>60 mm Hg). Primary outcomes were 30-day mortality and long-term
      survival. RESULTS: There were no significant between-group differences in age or
      preoperative comorbidities. Mitral valve surgery included mitral valve
      replacement (78%) and repair (22%). The severe PH group had more mitral valve
      replacement (81%; P = .04), severe tricuspid valve regurgitation (31%; P = .003),
      right heart failure (17%; P = .02), and concomitant tricuspid valve procedures
      (46%; P < .001). For severe PH, 30-day mortality was 9%, with no significant
      group differences. Ten- and 12-year survival were significantly worse in the
      moderate-severe PH group (58% and 51%, respectively) compared with the normal PAP
      mild PH group (83% and 79%, respectively) with a hazard ratio of 2.98 (95%
      confidence interval, 1.55-5.75; P = .001). Ten-year survival after mitral valve
      surgery for mitral stenosis was inversely associated with preoperative PAP.
      CONCLUSIONS: Mitral valve surgery can be performed with acceptable 30-day
      mortality for patients with mitral stenosis and moderate to severe PH, but long
      term survival is impaired by moderate to severe PH. Patients with mitral stenosis
      and mild PH (systolic PAP 35-44 mm Hg) should be considered for mitral valve
      surgery.

PMID- 27045045
TI  - Formation of Copper Catalysts for CO2 Reduction with High Ethylene/Methane
      Product Ratio Investigated with In Situ X-ray Absorption Spectroscopy.
AB  - Nanostructured copper cathodes are among the most efficient and selective
      catalysts to date for making multicarbon products from the electrochemical carbon
      dioxide reduction reaction (CO2RR). We report an in situ X-ray absorption
      spectroscopy investigation of the formation of a copper nanocube CO2RR catalyst
      with high activity that highly favors ethylene over methane production. The
      results show that the precursor for the copper nanocube formation is copper(I)
      oxide, not copper(I)-chloride as previously assumed. A second route to an
      electrochemically similar material via a copper(II)-carbonate/hydroxide is also
      reported. This study highlights the importance of using oxidized copper
      precursors for constructing selective CO2 reduction catalysts and shows the
      precursor oxidation state does not affect the electrocatalyst selectivity toward
      ethylene formation. 

PMID- 27045046
TI  - Adapting photosynthesis to the near-infrared: non-covalent binding of
      phycocyanobilin provides an extreme spectral red-shift to phycobilisome core
      membrane linker from Synechococcus sp. PCC7335.
AB  - Phycobiliproteins that bind bilins are organized as light-harvesting complexes,
      phycobilisomes, in cyanobacteria and red algae. The harvested light energy is
      funneled to reaction centers via two energy traps, allophycocyanin B and the core
      membrane linker, ApcE1 (conventional ApcE). The covalently bound phycocyanobilin
      (PCB) of ApcE1 absorbs near 660 nm and fluoresces near 675 nm. In cyanobacteria
      capable of near infrared photoacclimation, such as Synechococcus sp. PCC7335,
      there exist even further spectrally red shifted components absorbing >700 nm and
      fluorescing >710 nm. We expressed the chromophore domain of the extra core
      membrane linker from Synechococcus sp. PCC7335, ApcE2, in E. coli together with
      enzymes generating the chromophore, PCB. The resulting chromoproteins, PCB
      ApcE2(1-273) and the more truncated PCB-ApcE2(24-245), absorb at 700 nm and
      fluoresce at 714 nm. The red shift of ~40 nm compared with canonical ApcE1
      results from non-covalent binding of the chromophore by which its full
      conjugation length including the Delta3,3(1) double bond is preserved. The
      extreme spectral red-shift could not be ascribed to exciton coupling: dimeric PCB
      ApcE2(1-273) and monomeric-ApcE2(24-245) absorbed and fluoresced similarly.
      Chromophorylation of ApcE2 with phycoerythrobilin- or phytochromobilin resulted
      in similar red shifts (absorption at 615 and 711 nm, fluorescence at 628 or 726
      nm, respectively), compared to the covalently bound chromophores. The self
      assembled non-covalent chromophorylation demonstrates a novel access to red and
      near-infrared emitting fluorophores. Brightly fluorescent biomarking was
      exemplified in E. coli by single-plasmid transformation.

PMID- 27045047
TI  - Baseline concentration of Polonium-210 ((210)Po) in tuna fish.
AB  - Several species of tuna fish were analyzed for (210)Po content in their edible
      muscle tissues. This study was carried out as a part of baseline data generation
      around a large nuclear power plant situated at Kudankulam, southeast coast of
      India. The concentration of (210)Po in the muscle tissue ranged from 40.9+/-5.2
      to 92.5+/-7.9Bq/kg of fresh fish, and the highest activity was recorded for the
      tuna Euthynnus affinis and the lowest for Auxis thazard. The committed effective
      dose to the local residents was calculated to be 62.7-141.8MUSvyear(-1). 

PMID- 27045048
TI  - Comparison of wastewater-associated contaminants in the bed sediment of Hempstead
      Bay, New York, before and after Hurricane Sandy.
AB  - Changes in bed sediment chemistry of Hempstead Bay (HB) have been evaluated in
      the wake of Hurricane Sandy, which resulted in the release of billions of liters
      of poorly-treated sewage into tributaries and channels throughout the bay.
      Surficial grab samples (top 5cm) collected before and (or) after Hurricane Sandy
      from sixteen sites in HB were analyzed for 74 wastewater tracers and steroid
      hormones, and total organic carbon. Data from pre- and post-storm comparisons of
      the most frequently detected wastewater tracers and ratios of steroid hormone and
      of polycyclic aromatic hydrocarbon concentrations indicate an increased sewage
      signal near outfalls and downstream of where raw sewage was discharged. Median
      concentration of wastewater tracers decreased after the storm at sites further
      from outfalls. Overall, changes in sediment quality probably resulted from a
      combination of additional sewage inputs, sediment redistribution, and stormwater
      runoff in the days to weeks following Hurricane Sandy. 

PMID- 27045049
TI  - Primary proximal epithelioid sarcoma of the lung successfully treated with
      pneumonectomy and adjuvant chemotherapy.
AB  - Primary sarcomas of the lung and proximal epithelial sarcomas (PESs) are
      extremely rare. Inactivation of INI1 has been found in the majority of
      epithelioid sarcoma (ES). We report the third known case of a primary PES of the
      lung along with immunohistochemical data. A 41-year-old man with HIV infection,
      on highly active antiretroviral therapy, presented with haemoptysis, shortness of
      breath and progressive weight loss for 2 months. He was eventually diagnosed with
      stage IIA cT2bN0M0 grade-2 primary PES of the lung. This patient underwent
      pneumonectomy and adjuvant chemotherapy with ifosfamide and doxorubicin. He
      remains in remission 36 months since diagnosis. Our case stands to help other
      clinicians as treatment of such rare cases is often reliant on case reports. We
      also posit a possible pathogenic mechanism given a history of HIV infection in
      this patient. The association of INI1 mutation with other atypical sarcomas in
      patients with HIV infection merits further evaluation.

PMID- 27045050
TI  - Primary malignant mesothelioma of the spermatic cord.
AB  - Primary spermatic cord malignant mesothelioma is an extremely rare tumour with
      only 12 cases reported so far. It is an aggressive tumour with a high recurrence
      rate. A 45-year-old man presented with a slow growing right inguinal swelling for
      the past 1 year. Physical examination revealed a well-circumscribed, hard, non
      reducible swelling palpable along the medial extent of the inguinal canal with no
      cough impulse. Fine-needle aspiration cytology suggested metastatic carcinoma.
      Contrast-enhanced CT of the thorax and abdomen did not reveal any primary. Right
      high inguinal orchidectomy was performed at another institution. Postoperative
      histopathological examination (HPE) and immunohistochemistry suggested biphasic
      malignant mesothelioma with resected margin positive. The patient was referred to
      us for revision surgery and adjuvant therapy. Postoperative course was
      uneventful. Currently, he is undergoing radiotherapy.Surgery is the first-line
      treatment. Patients should receive adjuvant radiotherapy and/or chemotherapy and
      long-term follow-up surveillance.

PMID- 27045051
TI  - Middle lobe syndrome: a singularly rare presentation of complicated pulmonary
      hydatid disease.
AB  - Imaging is crucial to the diagnosis of pulmonary hydatid disease, as it is often
      the first modality that raises suspicion of the disease. Middle lobe syndrome
      (MLS) as a presentation of this disease is a distinct rarity. A 45-year-old
      woman, a never-smoker, presented with cough and streaky haemoptysis. Imaging
      demonstrated a trapezoidal opacity with its base towards the hilum and contiguous
      with the right cardiac border. The reformatted sagittal view confirmed the
      diagnosis of MLS. Fibreoptic bronchoscopy (FOB) revealed an avascular white
      membranous structure wholly occluding the medial segment of the middle lobe. This
      was completely removed through gentle suction. Bronchial aspirate revealed
      hooklets of hydatid and echinococcal serology was positive. Subsequently, three
      cycles of albendazole were administered with remarkable clinical and radiological
      improvement. To the best of our knowledge, this is the first detailed description
      of MLS caused by pulmonary hydatidosis that was completely removed through FOB. 

PMID- 27045052
TI  - Beware the yellow slimming pill: fatal 2,4-dinitrophenol overdose.
AB  - An industrial chemical, 2,4-dinitrophenol (DNP), has found use as a weight loss
      drug. It is extremely toxic in overdose and has a narrow therapeutic window with
      significant interindividual variability in metabolism. The rise in internet-based
      sales and distribution of this drug has seen an increased incidence of both
      accidental and intentional overdose presenting to emergency departments across
      the UK. No antidote currently exists and overdose is often fatal despite
      management based on current recommendations. We report a case of intentional
      overdose of DNP in a young man and discuss the current treatment guidelines. The
      case highlights the need for an increased awareness among frontline medical staff
      of the effects of DNP poisoning and questions the need for a more aggressive
      approach in the management of acute toxicity. 

PMID- 27045053
TI  - Carbimazole-induced exudative pleural effusions.
AB  - Carbimazole, an antithyroid drug, is associated with a significant number of side
      effects, but pleuropulmonary complications are rare. We report the case of a 42
      year-old Caucasian man who developed dyspnoea secondary to bilateral exudative
      pleural effusions while on carbimazole therapy. Extensive investigations,
      including a vasculitic screen, ruled out other potential causes for this
      patient's clinical presentation. This patient's pleural effusions gradually
      resolved within a few months of stopping carbimazole therapy, suggesting a role
      for the latter in the aetiopathogenesis of his presentation. Clinicians should
      consider discontinuing treatment with carbimazole and introducing alternative
      antithyroid therapy in this setting, once other potential causes of a pleural
      effusion have been systematically ruled out. 

PMID- 27045054
TI  - Urethro-venous intravasation: a rare complication of retrograde urethrogram.

PMID- 27045055
TI  - Induced knockouts provide insights into human L1 syndrome.

PMID- 27045056
TI  - Public health officials alarmed at spread of Zika virus.

PMID- 27045057
TI  - Drug disposal kiosks help hospitals serve their community.

PMID- 27045058
TI  - Substances doubtful for bulk drug substances list could be INDs.

PMID- 27045059
TI  - The costs of prescription drugs in the United States: Pharmacists' voices must be
      heard.

PMID- 27045060
TI  - Drug alerts and the Goldilocks principle: Striving for "just right".

PMID- 27045061
TI  - Making the transition from pharmacy student to resident.

PMID- 27045062
TI  - Optimization of clinical decision support through minimization of excessive drug
      allergy alerts.

PMID- 27045063
TI  - Once-daily aminoglycosides.

PMID- 27045064
TI  - Once-daily aminoglycosides.

PMID- 27045065
TI  - Once-daily aminoglycosides.

PMID- 27045066
TI  - Selecting a polyclonal immune globulin treatment for a patient with primary
      immune deficiency disease: Role of the clinical pharmacist.
AB  - PURPOSE: Considerations for selecting an immune globulin treatment, transitioning
      patients with primary immune deficiency disease who are receiving long-term
      treatment between settings of care, and the role of the pharmacist in these
      endeavors are described. SUMMARY: Numerous immune globulin formulations are
      commercially available, and these formulations differ in immune globulin
      concentration, stabilizing additives, trace non-immune globulin proteins, and the
      manufacturing process, all of which may elicit different adverse reactions in
      patients. Patients may also exhibit differences in tolerability to the route of
      administration. The complex process of formulating, establishing, and maintaining
      an immune globulin treatment regimen requires the participation of the patient
      and healthcare providers. For patients transitioning between settings of care,
      particular attention must be paid to any changes to a treatment that has been
      individualized for a patient. Factors affecting the decision process include
      medical history, immune globulin formulation characteristics, formulary stock,
      payer formulary, and patient preference. For patients switching between immune
      globulin formulations or routes of administration, dosage adjustments of and
      tolerance to immune globulin may be important considerations. A clinical
      pharmacist with knowledge of the pharmaceutical suitability of immune globulin
      formulations can safely facilitate these transitions. CONCLUSION: Selecting a
      route of administration for and formulation of immune globulin involves the
      consideration of many factors, including the patient's medical history,
      formulation characteristics, formulary stock, payer formulary, and patient
      preference. A pharmacist is essential in helping the patient navigate the
      decision-making process and in coordinating care and communication among
      patients, caregivers, and healthcare providers to monitor patient progress and
      adherence and ensure safe and efficient transitions of care.

PMID- 27045067
TI  - Novel plasminogen and hyaluronate sodium eye drop formulation for a patient with
      ligneous conjunctivitis.
AB  - PURPOSE: The development, analysis, and first clinical use of a novel eye drop
      formulation of plasminogen and hyaluronate sodium for the treatment of a patient
      with ligneous conjunctivitis (LC) are described. SUMMARY: LC is a chronic
      inflammatory disorder of the eye that can in rare cases lead to corneal
      involvement and subsequent blindness. Topically administered plasminogen is an
      effective treatment for LC; however, the lack of a specific and validated
      formulation of plasminogen for topical treatment can constitute a gap in the
      quality of care. A novel formulation of plasminogen and hyaluronate sodium for
      the treatment of LC was developed by combining commercially available products.
      Through a series of tests, including microbiological, viscosity, and pH analyses,
      the novel eye drop formulation was demonstrated to have constant activity (3.3
      IU/mL or greater), to be microbiologically stable (i.e., sterile), and to be safe
      enough for daily administration. The first clinical application of the novel eye
      drop formulation was in the case of a nine-year-old girl with LC affecting both
      eyes. Initially, the girl's parents administered two drops every three hours to
      the left eye each day while the girl was awake. On examination after 30 days of
      daily use of the eye drop formulation, the patient was found to have a clear
      cornea and no membrane development on the conjunctiva; the formulation was
      subsequently administered in both eyes, with positive results. CONCLUSION: A new
      formulation of plasminogen plus hyaluronate sodium was developed, tested, and
      used successfully in a girl with LC.

PMID- 27045068
TI  - Influence of apixaban on antifactor Xa levels in a patient with acute kidney
      injury.
AB  - PURPOSE: The case of a patient requiring conversion from apixaban to heparin in
      the setting of acute kidney injury is reported. SUMMARY: A 70-year-old man was
      initiated on apixaban 5 mg twice daily for new-onset, nonvalvular atrial
      fibrillation with a CHA2DS2-VASc score of 4, indicating a high risk of stroke.
      Soon after starting apixaban, he experienced pulmonary edema with pneumonia
      requiring hospitalization. During the course of hospitalization, the patient
      developed acute kidney injury requiring hemodialysis, and apixaban was stopped
      due to concerns about altered pharmacokinetics and impaired drug elimination in
      this setting. A heparin infusion was started 36 hours after the last dose of
      apixaban was administered. Antifactor Xa levels were monitored consistent with
      the hospital's standard practice protocols. The initial and repeat antifactor Xa
      concentrations were elevated (1.8-4.4 IU/mL) for up 72 hours after stopping the
      heparin infusion. Given the suspected interference of apixaban with standard
      antifactor Xa level monitoring, the heparin protocol was modified to reflect drip
      rate adjustments based on activated partial thromboplastin times (aPTTs). The
      hospital protocol for heparin infusions was reinstituted on hospital day 7, with
      dosage adjustments based on antifactor Xa levels. The patient remained on a
      continuous heparin infusion for atrial fibrillation for the remainder of his
      hospitalization without complications or bleeding events. CONCLUSION: A 70-year
      old man with new-onset nonvalvular atrial fibrillation and receiving apixaban
      discontinued this therapy and was given heparin instead due to acute kidney
      injury. His heparin dosage was successfully adjusted based on antifactor Xa
      levels and aPPTs.

PMID- 27045069
TI  - Comparison of indexing times among articles from medical, nursing, and pharmacy
      journals.
AB  - PURPOSE: Results of an analysis of the times to indexing of articles published in
      medical, nursing, and pharmacy journals are reported. METHODS: MEDLINE data were
      retrieved for articles published in selected general practice medical, nursing,
      and pharmacy journals and entered into the PubMed system in 2012 and 2013.
      Collected data included PubMed entry date, date of indexing with Medical Subject
      Headings (MeSH) terms, and publication characteristics. Survival analysis was
      performed to assess the primary outcome of time to indexing. Cox proportional
      hazards models were developed to assess the effect of healthcare discipline and
      source journal on the primary outcome. RESULTS: Data were collected for 19,259
      articles, of which 78.7%, 12.6%, and 8.7% originated from medical, nursing, and
      pharmacy journals, respectively. For medical, pharmacy, and nursing journals,
      97.8%, 90.8%, and 50.1% of articles, respectively, were indexed within one year
      of PubMed entry; the corresponding median (interquartile range) times to indexing
      were 52 (20-68), 186 (150-246), and 252 (168-301) days. Unadjusted hazard ratios
      derived from Cox models indicated that indexing within one year was significantly
      less likely for articles published in pharmacy or nursing journals versus medical
      journals and for articles from all evaluated journals versus a designated
      reference publication (New England Journal of Medicine). CONCLUSION: Analysis of
      major medical, nursing, and pharmacy journals found that articles from nursing
      and pharmacy journals were indexed with MeSH terms more slowly than articles from
      medical journals. Journal identity was significantly associated with time to
      indexing.

PMID- 27045070
TI  - Recommendations for selecting drug-drug interactions for clinical decision
      support.
AB  - PURPOSE: Recommendations for including drug-drug interactions (DDIs) in clinical
      decision support (CDS) are presented. SUMMARY: A conference series was conducted
      to improve CDS for DDIs. A work group consisting of 20 experts in pharmacology,
      drug information, and CDS from academia, government agencies, health information
      vendors, and healthcare organizations was convened to address (1) the process to
      use for developing and maintaining a standard set of DDIs, (2) the information
      that should be included in a knowledge base of standard DDIs, (3) whether a list
      of contraindicated drug pairs can or should be established, and (4) how to more
      intelligently filter DDI alerts. We recommend a transparent, systematic, and
      evidence-driven process with graded recommendations by a consensus panel of
      experts and oversight by a national organization. We outline key DDI information
      needed to help guide clinician decision-making. We recommend judicious
      classification of DDIs as contraindicated and more research to identify methods
      to safely reduce repetitive and less-relevant alerts. CONCLUSION: An expert panel
      with a centralized organizer or convener should be established to develop and
      maintain a standard set of DDIs for CDS in the United States. The process should
      be evidence driven, transparent, and systematic, with feedback from multiple
      stakeholders for continuous improvement. The scope of the expert panel's work
      should be carefully managed to ensure that the process is sustainable. Support
      for research to improve DDI alerting in the future is also needed. Adoption of
      these steps may lead to consistent and clinically relevant content for
      interruptive DDIs, thus reducing alert fatigue and improving patient safety.

PMID- 27045072
TI  - Actions of the ASHP Board of Directors-Meeting of January 21-22, 2016.

PMID- 27045071
TI  - ASHP professional policy recommendations-Invitation to comment.

PMID- 27045073
TI  - Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large International
      Population-Based Study.
AB  - Maternal cigarette smoking is a well-established risk factor for oral clefts.
      Evidence is less clear for passive (secondhand) smoke exposure. We combined
      individual-level data from 4 population-based studies (the Norway Facial Clefts
      Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the
      Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth
      Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases
      and 9,626 controls. We categorized first-trimester passive and active smoke
      exposure. Multivariable logistic models adjusted for possible confounders
      (maternal alcohol consumption, use of folic acid supplements, age, body size,
      education, and employment, plus study fixed effects). Children whose mothers
      actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95%
      confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking
      mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk
      was further elevated among babies of smoking mothers who were exposed to passive
      smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a
      modest association between first-trimester passive smoking and oral clefts that
      was consistent across populations, diverse study designs, and cleft subtypes.
      While this association may reflect subtle confounding or bias, we cannot rule out
      the possibility that passive smoke exposure during pregnancy is teratogenic.

PMID- 27045074
TI  - History of Severe Sunburn and Risk of Skin Cancer Among Women and Men in 2
      Prospective Cohort Studies.
AB  - Few studies have assessed the relationship between sunburn and risk of different
      skin cancers (melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma
      (BCC)) in prospective studies simultaneously, and little is known about the
      association of severe sunburns at different body sites with skin cancer risk. We
      used data on 87,166 women in the Nurses' Health Study (1982-2010) and 32,959 men
      in the Health Professionals Follow-up Study (1992-2010) to investigate skin
      cancer risk associated with history of severe sunburns at different body sites
      (face/arms, trunk, and lower limbs). After adjustment for other risk factors,
      overall baseline history of severe sunburn was more apparently associated with
      risk of melanoma than with risk of SCC and BCC in men (multivariable-adjusted
      hazard ratios were 2.41 (95% confidence interval (CI): 1.32, 4.41) for melanoma,
      1.48 (95% CI: 1.08, 2.03) for SCC, and 1.18 (95% CI: 1.06, 1.32) for BCC) but not
      in women. Sunburn on the trunk appeared to be more closely associated with
      melanoma risk, but not risk of SCC and BCC, when compared with sunburns at other
      body sites (face/arms and lower limbs). These differences were more apparent in
      men than in women. Pending further investigation, our findings add novel insights
      to the existing literature on sunburn history and skin cancer risk.

PMID- 27045075
TI  - [Central nervous system involvement in patients with hematologic malignancies: A
      comparative study of conventional cytology with versus flow cytometry].

PMID- 27045076
TI  - [Genetics of Behcet disease].

PMID- 27045077
TI  - Computational modelling of placental amino acid transfer as an integrated system.
AB  - Placental amino acid transfer is essential for fetal development and its
      impairment is associated with poor fetal growth. Amino acid transfer is mediated
      by a broad array of specific plasma membrane transporters with overlapping
      substrate specificity. However, it is not fully understood how these different
      transporters work together to mediate net flux across the placenta. Therefore the
      aim of this study was to develop a new computational model to describe how human
      placental amino acid transfer functions as an integrated system. Amino acid
      transfer from mother to fetus requires transport across the two plasma membranes
      of the placental syncytiotrophoblast, each of which contains a distinct
      complement of transporter proteins. A compartmental modelling approach was
      combined with a carrier based modelling framework to represent the kinetics of
      the individual accumulative, exchange and facilitative classes of transporters on
      each plasma membrane. The model successfully captured the principal features of
      transplacental transfer. Modelling results clearly demonstrate how modulating
      transporter activity and conditions such as phenylketonuria, can increase the
      transfer of certain groups of amino acids, but that this comes at the cost of
      decreasing the transfer of others, which has implications for developing clinical
      treatment options in the placenta and other transporting epithelia. 

PMID- 27045078
TI  - Computer simulations suggest direct and stable tip to tip interaction between the
      outer membrane channel TolC and the isolated docking domain of the multidrug RND
      efflux transporter AcrB.
AB  - One way by which bacteria achieve antibiotics resistance is preventing drug
      access to its target molecule for example through an overproduction of multi-drug
      efflux pumps of the resistance nodulation division (RND) protein super family of
      which AcrAB-TolC in Escherichia coli is a prominent example. Although
      representing one of the best studied efflux systems, the question of how AcrB and
      TolC interact is still unclear as the available experimental data suggest that
      either both proteins interact in a tip to tip manner or do not interact at all
      but are instead connected by a hexamer of AcrA molecules. Addressing the question
      of TolC-AcrB interaction, we performed a series of 100 ns - 1 us-molecular
      dynamics simulations of membrane-embedded TolC in presence of the isolated AcrB
      docking domain (AcrB(DD)). In 5/6 simulations we observe direct TolC-AcrB(DD)
      interaction that is only stable on the simulated time scale when both proteins
      engage in a tip to tip manner. At the same time we find TolC opening and closing
      freely on extracellular side while remaining closed at the inner periplasmic
      bottleneck region, suggesting that either the simulated time is too short or
      additional components are required to unlock TolC.

PMID- 27045079
TI  - Metastasis of lobular breast cancer to endometrial polyps with and without the
      presence of vaginal bleeding.

PMID- 27045080
TI  - PKM2 Thr454 phosphorylation increases its nuclear translocation and promotes
      xenograft tumor growth in A549 human lung cancer cells.
AB  - Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis which is highly expressed
      in many tumor cells, and plays an important role in the Warburg effect. In
      previous study, we found PIM2 phosphorylates PKM2 at Thr454 residue (Yu, etl
      2013). However, the functions of PKM2 Thr454 modification in cancer cells still
      remain unclear. Here we find PKM2 translocates into the nucleus after Thr454
      phosphorylation. Replacement of wild type PKM2 with a mutant (T454A) enhances
      mitochondrial respiration, decreases pentose phosphate pathway, and enhances
      chemosensitivity in A549 cells. In addition, the mutant (T454A) PKM2 reduces
      xenograft tumor growth in nude mice. These findings demonstrate that PKM2 T454
      phosphorylation is a potential therapeutic target in lung cancer.

PMID- 27045081
TI  - CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody
      hinder murine T helper cell activities.
AB  - Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been reported to
      lead to antigen-specific immunotolerance in allograft transplantation and
      autoimmune diabetes, as well as possibly to inhibition of allergic inflammation
      in mice. However, the molecular mechanisms underlying hyporesponsive T cell
      responses induced by YTS177 MoAb remain elusive. Herein, we demonstrate that the
      YTS177 MoAb increases the levels of anergy factors p27(kip1) and Cbl-b, inhibits
      IL-2 production, and impairs calcium mobilization in activated T cells in vitro.
      YTS177 MoAb suppresses OVA-driven proliferation of DO11.10 CD4(+) T cells in vivo
      as well. Mechanistically, YTS177 MoAb induces tolerance by causing CD4 down
      regulation through clathrin-dependent and raft dissociation. The results obtained
      in this study lead us to propose novel protective or curative approaches to CD4 T
      cell-mediated diseases.

PMID- 27045082
TI  - MAGE-A1 promotes melanoma proliferation and migration through C-JUN activation.
AB  - MAGE-A1 belongs to the chromosome X-clustered genes of cancer-testis antigen
      family and is normally expressed in the human germ line but is also overexpressed
      in various tumors. Previous studies of MAGE-A1 in melanoma mainly focused on
      methylation changes or its role in immunotherapy, however, its biological
      functions in melanoma have remained unknown. In order to determine the role of
      MAGE-A1 in melanoma growth and metastasis, we manipulated melanoma cell lines
      with overexpression and knockdown of MAGE-A1. Integration of cell proliferation
      assays, transwell migration and invasion assays, and RNA-Seq analysis revealed
      that up-regulation of MAGE-A1 dramatically promoted proliferation, migration, and
      invasion of human melanoma cell lines in vitro, while down-regulation of MAGE-A1
      inhibited those characteristics associated with tumor cells. Furthermore,
      transcriptome sequencing revealed that MAGE-A1 exerts its tumor promoting
      activity by activating p-C-JUN directly or through ERK-MAPK signaling pathways.
      Based on our findings, we propose that MAGE-A1 may be a potential therapeutic
      target for melanoma patients.

PMID- 27045083
TI  - Ischemic Preconditioning protects hepatocytes from ischemia-reperfusion injury
      via TGR5-mediated anti-apoptosis.
AB  - Ischemic preconditioning (IP) has been shown to protect hepatic tissue from liver
      ischemia-reperfusion injury (IRI). TGR5, as a new-type bile acid receptor, has
      been shown protective roles in several liver diseases. However, the relationship
      between TGR5 and IP is still unknown. This study investigated effects of IP on
      TGR5 as well as the roles of TGR5 on hepatic tissue lesions and apoptosis in
      liver IRI. We showed that TGR5 was significantly upregulated in liver tissues
      after IP. To further analyzed effects of the TGR5 on liver IRI, wild type and
      TGR5 knockout mice were used to establish the liver IRI model. IP effectively
      alleviated liver IRI, but TGR5 deficiency significantly neutralized IP-related
      liver protection, as evidenced by serum alanine aminotransferase levels,
      histological liver damage, hepatocellular apoptosis and cytokines expressions. In
      addition, molecules related to apoptosis were detected by Western Blot, which
      showed that activation of TGR5 by IP increased expression of Bcl-2, and inhibited
      expressions of IRAK4 and cleaved caspase-3, but TGR5 deficiency abolished IP
      induced expressions of anti-apoptosis molecule. In vitro, effects of TGR5 on
      hepatocytes were further analyzed by TGR5 agonist (INT-777) and
      hypoxia/reoxygenation (H/R), which displayed that INT-777 markedly attenuated H/R
      induced hepatocellular apoptosis. In conclusion, our study indicates that IP
      alleviates hepatocellular apoptosis, and reduces liver IRI through TGR5-mediated
      anti-apoptosis functions.

PMID- 27045084
TI  - MEK1/2 inhibitors induce interleukin-5 expression in mouse macrophages and
      lymphocytes.
AB  - Uptake of oxidized low-density lipoprotein (oxLDL) by macrophages facilitates the
      formation of foam cells, the prominent part of atherosclerotic lesions.
      Interleukin-5 (IL-5) is a cytokine regulating interactions between immune cells.
      It also activates the production of T15/EO6 IgM antibodies in B-1 cells, which
      can bind oxLDL thereby demonstrating anti-atherogenic properties. We previously
      reported that inhibition of extracellular signal-regulated kinases 1 and 2
      (ERK1/2) by mitogen-activated protein kinase kinases 1/2 (MEK1/2) inhibitors can
      reduce atherosclerosis. In this study, we determined the effects of MEK1/2
      inhibitors on IL-5 production both in vitro and in vivo. In vitro, MEK1/2
      inhibitors (PD98059 and U0126) substantially inhibited phosphorylation of MEK1/2
      and ERK1/2. Associated with inhibition of ERK1/2 phosphorylation both in vitro
      and in vivo, MEK1/2 inhibitors induced IL-5 protein expression in macrophages
      (RAW macrophages and peritoneal macrophages) and lymphocytes (EL-4 cells). In
      vivo, administration of mice with MEK1/2 inhibitors increased serum IL-5 levels,
      and IL-5 protein expression in mouse spleen and liver. At the mechanistic level,
      we determined that MEK1/2 inhibitors activated IL-5 mRNA expression and IL-5
      promoter activity in the liver X receptor (LXR) dependent manner indicating the
      induction of IL-5 transcription. In addition, we determined that MEK1/2
      inhibitors enhanced IL-5 protein stability. Taken together, our study
      demonstrates that MEK1/2 inhibitors induce IL-5 production which suggests another
      anti-atherogenic mechanism of MEK1/2 inhibitors.

PMID- 27045085
TI  - MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous
      cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive
      malignancies in the gastrointestinal tract. Emerging studies have indicated that
      microRNAs (miRNAs) are strongly implicated in the development and progression of
      ESCC. Here, we focused on the function and the underlying molecular mechanism of
      miR-202 in ESCC. The results showed that miR-202 was significantly down-regulated
      in ESCC tissues and cell lines. Overexpression of miR-202 in ECa-109 and KYSE-510
      cells markedly suppressed cell proliferation and cell migration, and induced cell
      apoptosis. Furthermore, laminin alpha1 (LAMA1) expression was frequently positive
      in ESCC tissues and inversely correlated with miR-202 expression. Then we
      demonstrated that miR-202 targeted 3'-untranslated region (UTR) of LAMA1 and
      inhibited its protein expression. Additionally, LAMA1 overexpression rescued the
      proliferation inhibition and cell apoptosis elevation induced by miR-202. MiR-202
      also inhibited the protein expression of p-FAK and p-Akt, which were all reversed
      by LAMA1 overexpression. Taken together, these findings suggest that miR-202 may
      function as a novel tumor suppressor in ESCC by repressing cell proliferation and
      migration, and its biological effects may attribute the inhibition of LAMA1
      mediated FAK-PI3K-Akt signaling.

PMID- 27045086
TI  - Outcomes of Hip Arthroscopic Surgery in Patients With Tonnis Grade 1
      Osteoarthritis With a Minimum 2-Year Follow-up: Evaluation Using a Matched-Pair
      Analysis With a Control Group With Tonnis Grade 0.
AB  - BACKGROUND: There are limited studies on the effect of mild osteoarthritis (OA)
      on outcomes of hip arthroscopic surgery. PURPOSE: To conduct a matched-pair
      analysis with a minimum 2-year follow-up to evaluate outcomes after hip
      arthroscopic surgery in patients with Tonnis grade 1 OA. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: Data were prospectively collected on
      patients who underwent hip arthroscopic surgery between April 2008 and December
      2012. Patients were excluded if they had previous hip conditions. The remaining
      patients were divided into either Tonnis 0 or 1 grade OA groups and were matched
      in a 1-to-1 ratio according to age within 5 years, sex, body mass index category,
      labral treatment, and capsular treatment. Four patient-reported outcome (PRO)
      scores, as well as the visual analog scale (VAS) score for pain, patient
      satisfaction, and rates of revision arthroscopic surgery and conversion to total
      hip arthroplasty (THA), were recorded. RESULTS: A total of 1412 hip arthroscopic
      procedures were performed during the study period, of which 1036 met the
      inclusion criteria and 892 (86.1%) had 2-year follow-up. There were 738 and 154
      patients with Tonnis grade 0 and 1, respectively; 93 patients were matched in
      each group. The Tonnis grade 0 group had a mean follow up of 28.7 months (range,
      23.5-67.9 months), and the Tonnis grade 1 group had a mean follow up of 31.5
      months (range, 23.6-63.5 months). Both groups demonstrated a significant
      improvement in all PROs and the VAS at a minimum 2-year follow-up. For the Tonnis
      grade 0 group, the improvements (in points) in the PROs were as follows: modified
      Harris Hip Score (mHHS), 15.51; Nonarthritic Hip Score (NAHS), 20.65; Hip Outcome
      Score-Activities of Daily Living (HOS-ADL), 16.83; and Hip Outcome Score-Sport
      Specific Subscale (HOS-SSS), 20.91. The VAS score for the Tonnis grade 0 group
      decreased by 2.82 points. For the Tonnis grade 1 group, the improvements (in
      points) in the PROs were as follows: mHHS, 19.52; NAHS, 20.96; HOS-ADL, 18.20;
      and HOS-SSS, 21.61. The VAS score for the Tonnis grade 1 group decreased by 2.84
      points. No significant difference was found between the mean change in PROs, VAS,
      or patient satisfaction between the groups (P > .05). There was no significant
      difference in subsequent rates for revision arthroscopic surgery or conversion to
      THA between the groups (P = .3 and .6, respectively). The rates for revision
      arthroscopic surgery and conversion to THA were 9.68% and 9.68%, respectively, in
      the Tonnis grade 0 group and 5.38% and 11.83%, respectively, in the Tonnis grade
      1 group. CONCLUSION: At 2-year follow-up, patients with Tonnis grade 1 OA had
      improved outcomes after hip arthroscopic surgery, with no significant difference
      compared with a matched control group of patients with Tonnis grade 0 OA.
      However, further studies are underway to determine if the results of the Tonnis
      grade 1 cohort will deteriorate over longer term follow-up.

PMID- 27045087
TI  - Surgical Trends in the Treatment of Meniscal Tears: Analysis of Data From the
      American Board of Orthopaedic Surgery Certification Examination Database.
AB  - BACKGROUND: The indications and criteria for meniscal repair are expanding in
      parallel with new understanding in biomechanics, joint pathophysiology, and
      increased physician education. PURPOSE: To describe the practice patterns of
      arthroscopic meniscal treatment in recent years, compare the trends of
      arthroscopic meniscal repair versus arthroscopic meniscectomy, and compare sports
      fellowship-trained versus non-sports fellowship-trained surgeons in terms of
      arthroscopic meniscal treatment techniques among American Board of Orthopaedic
      Surgery (ABOS) candidates from 2004 to 2012. STUDY DESIGN: Descriptive
      epidemiology study. METHODS: The ABOS database was used to identify cases of
      meniscal repair, partial meniscectomy, and anterior cruciate ligament (ACL)
      reconstruction from 2004 to 2012. The number of surgeons contributing cases for
      each calendar year was also recorded, along with the number who had sports
      fellowship training. Rates were calculated as the number of procedures per
      surgeon per year. Trends were analyzed using Poisson regression analysis to model
      the rate of each procedure over time. RESULTS: The rate of all meniscal
      procedures per surgeon decreased 12% from 18.4 cases per surgeon in 2004 to 16.2
      cases per surgeon in 2012. There was a smaller decrease for sports fellowship
      trained surgeons (7%) than for non-sports fellowship-trained surgeons (32%). The
      rate of meniscal repair cases per surgeon increased 37% from 1.6 to 2.2 cases per
      surgeon. The rate of meniscectomy cases decreased 17% from 16.8 to 14.0 cases per
      surgeon. When comparing fellowship-trained surgeons to non-fellowship-trained
      surgeons, there was no significant difference in meniscal repair rates over time.
      There was a decrease of 35% in rates of meniscectomy among non-fellowship-trained
      surgeons compared with 11% among fellowship-trained surgeons. CONCLUSION: This
      study provides insight into the current practice trends of recent orthopaedic
      training graduates in the treatment of meniscal tears. The results suggest that
      reported meniscal procedures have decreased overall among ABOS candidates but
      that meniscal repair cases have increased. The findings support the recent shift
      toward evidence-based medicine, with changing practice patterns that may reflect
      the dissemination of recent findings from large, high-quality research studies in
      this field.

PMID- 27045088
TI  - Pediatric Anterior Cruciate Ligament Reconstruction: A Systematic Review of
      Transphyseal Versus Physeal-Sparing Techniques.
AB  - BACKGROUND: Anterior cruciate ligament reconstruction is becoming more common in
      skeletally immature individuals, and it may be performed with transphyseal or
      physeal-sparing techniques. A number of studies have assessed the outcomes of
      these techniques, but there is a need to systematically evaluate the pooled data
      from these studies. PURPOSE: To compare the differences in demographics and
      outcomes of transphyseal and physeal-sparing techniques by assessing (1)
      demographics, (2) incidence of growth disturbances, and (3) graft survivorship in
      the pediatric population. STUDY DESIGN: Systematic review. METHODS: A thorough
      review of 3 databases was performed to identify all studies that evaluated
      outcomes after pediatric reconstruction based on transphyseal or physeal-sparing
      techniques. After completing our search and cross-referencing for additional
      sources, 43 reports were identified for this review. Reports were analyzed for
      differences in demographics as well as incidence of leg-length discrepancies,
      angular deformities, and graft survivorship. After review of manuscripts, 27
      studies were included for review (21 transphyseal and 6 physeal-sparing studies).
      RESULTS: Those who had transphyseal reconstruction were more likely to be female
      (39% vs 20%; P = .0001), while those with the physeal-sparing surgery were
      younger (12 vs 13.5 years of age; P = .0001). The transphyseal and physeal
      sparing cohorts demonstrated similar incidence rates of leg-length discrepancies
      (0.81% vs 1.2%, respectively; P = .64) and angular deformities (0.61% vs 0%,
      respectively; P = .36). The transphyseal and physeal-sparing cohorts also showed
      similar rates of rerupture (6.2% vs 3.1%, respectively; P = .11). CONCLUSION:
      Although the study groups were not well matched with regard to age and sex, our
      results show that these surgical techniques have no differences in incidence of
      growth disturbances or graft survivorship. Younger males tend to undergo physeal
      sparing reconstruction. Future research should focus on long-term outcome metrics
      with the physeal-sparing techniques, as there remains a paucity of studies
      regarding them.

PMID- 27045089
TI  - Insights from the pollination drop proteome and the ovule transcriptome of
      Cephalotaxus at the time of pollination drop production.
AB  - BACKGROUND AND AIMS: Many gymnosperms produce an ovular secretion, the
      pollination drop, during reproduction. The drops serve as a landing site for
      pollen, but also contain a suite of ions and organic compounds, including
      proteins, that suggests diverse roles for the drop during pollination. Proteins
      in the drops of species of Chamaecyparis, Juniperus, Taxus, Pseudotsuga, Ephedra
      and Welwitschia are thought to function in the conversion of sugars, defence
      against pathogens, and pollen growth and development. To better understand
      gymnosperm pollination biology, the pollination drop proteomes of pollination
      drops from two species of Cephalotaxus have been characterized and an ovular
      transcriptome for C. sinensis has been assembled. METHODS: Mass spectrometry was
      used to identify proteins in the pollination drops of Cephalotaxus sinensis and
      C. koreana RNA-sequencing (RNA-Seq) was employed to assemble a transcriptome and
      identify transcripts present in the ovules of C. sinensis at the time of
      pollination drop production. KEY RESULTS: About 30 proteins were detected in the
      pollination drops of both species. Many of these have been detected in the drops
      of other gymnosperms and probably function in defence, polysaccharide metabolism
      and pollen tube growth. Other proteins appear to be unique to Cephalotaxus, and
      their putative functions include starch and callose degradation, among others.
      Together, the proteins appear either to have been secreted into the drop or to
      occur there due to breakdown of ovular cells during drop production. Ovular
      transcripts represent a wide range of gene ontology categories, and some may be
      involved in drop formation, ovule development and pollen-ovule interactions.
      CONCLUSIONS: The proteome of Cephalotaxus pollination drops shares a number of
      components with those of other conifers and gnetophytes, including proteins for
      defence such as chitinases and for carbohydrate modification such as beta
      galactosidase. Proteins likely to be of intracellular origin, however, form a
      larger component of drops from Cephalotaxus than expected from studies of other
      conifers. This is consistent with the observation of nucellar breakdown during
      drop formation in Cephalotaxus The transcriptome data provide a framework for
      understanding multiple metabolic processes that occur within the ovule and the
      pollination drop just before fertilization. They reveal the deep conservation of
      WUSCHEL expression in ovules and raise questions about whether any of the S-locus
      transcripts in Cephalotaxus ovules might be involved in pollen-ovule recognition.

PMID- 27045090
TI  - Modelling colour constancy in fish: implications for vision and signalling in
      water.
AB  - Colour vision and colour signals are important to aquatic animals, but light
      scattering and absorption by water distorts spectral stimuli. To investigate the
      performance of colour vision in water, and to suggest how photoreceptor spectral
      sensitivities and body colours might evolve for visual communication, we model
      the effects of changes in viewing distance and depth on the appearance of fish
      colours for three teleosts: a barracuda, Sphyraena helleri, which is dichromatic
      and two damselfishes, Chromis verater and Chromis hanui, which are trichromatic.
      We assume that photoreceptors light-adapt to the background, thereby implementing
      the von Kries transformation, which can largely account for observed colour
      constancy in humans and other animals, including fish. This transformation does
      not, however, compensate for light scattering over variable viewing distances,
      which in less than a metre seriously impairs dichromatic colour vision, and makes
      judgement of colour saturation unreliable for trichromats. The von Kries
      transformation does substantially offset colour shifts caused by changing depth,
      so that from depths of 0 to 30 m modelled colour changes (i.e. failures of colour
      constancy) are sometimes negligible. However, the magnitudes and directions of
      remaining changes are complex, depending upon the specific spectral sensitivities
      of the receptors and the reflectance spectra. This predicts that when judgement
      of colour is important, the spectra of signalling colours and photoreceptor
      spectral sensitivities should be evolutionarily linked, with the colours
      dependent on photoreceptor spectral sensitivities, and vice versa.

PMID- 27045091
TI  - Programming of the hypothalamic-pituitary-interrenal axis by maternal social
      status in zebrafish (Danio rerio).
AB  - The present study examined the effects of maternal social status, with
      subordinate status being a chronic stressor, on development and activity of the
      stress axis in zebrafish embryos and larvae. Female zebrafish were confined in
      pairs for 48 h to establish dominant/subordinate hierarchies; their offspring
      were reared to 144 h post-fertilization (hpf) and sampled at five time points
      over development. No differences were detected in maternal cortisol contribution,
      which is thought to be an important programmer of offspring phenotype. However,
      once zebrafish offspring began to synthesize cortisol de novo (48 hpf), larvae of
      dominant females exhibited significantly lower baseline cortisol levels than
      offspring of subordinate females. These lower cortisol levels may reflect reduced
      hypothalamic-pituitary-interrenal (HPI) axis activity, because corticotropin
      releasing factor (crf) and cytochrome p450 side chain cleavage enzyme (p450scc)
      mRNA levels also were lower in larvae from dominant females. Moreover, baseline
      mRNA levels of HPI axis genes continued to be affected by maternal social status
      beyond 48 hpf. At 144 hpf, stress-induced cortisol levels were significantly
      lower in offspring of subordinate females. These results suggest programming of
      stress axis function in zebrafish offspring by maternal social status,
      emphasizing the importance of maternal environment and experience on offspring
      stress axis activity.

PMID- 27045092
TI  - Odor-induced cAMP production in Drosophila melanogaster olfactory sensory
      neurons.
AB  - Insect odorant receptors are seven transmembrane domain proteins that form cation
      channels, whose functional properties such as receptor sensitivity are subject to
      regulation by intracellular signaling cascades. Here, we used the cAMP
      fluorescent indicator Epac1-camps to investigate the occurrence of odor-induced
      cAMP production in olfactory sensory neurons (OSNs) of Drosophila melanogaster We
      show that stimulation of the receptor complex with an odor mixture or with the
      synthetic agonist VUAA1 induces a cAMP response. Moreover, we show that while the
      intracellular Ca(2+) concentration influences cAMP production, the OSN-specific
      receptor OrX is necessary to elicit cAMP responses in Ca(2+)-free conditions.
      These results provide direct evidence of a relationship between odorant receptor
      stimulation and cAMP production in olfactory sensory neurons in the fruit fly
      antenna and show that this method can be used to further investigate the role
      that this second messenger plays in insect olfaction.

PMID- 27045093
TI  - The influence of nasal airflow on respiratory and olfactory epithelial
      distribution in felids.
AB  - The surface area of the maxilloturbinals and fronto-ethmoturbinals is commonly
      used as an osteological proxy for the respiratory and the olfactory epithelium,
      respectively. However, this assumption does not fully account for animals with
      short snouts in which these two turbinal structures significantly overlap,
      potentially placing fronto-ethmoturbinals in the path of respiratory airflow. In
      these species, it is possible that anterior fronto-ethmoturbinals are covered
      with non-sensory (respiratory) epithelium instead of olfactory epithelium. In
      this study, we analyzed the distribution of olfactory and non-sensory,
      respiratory epithelia on the turbinals of two domestic cats (Felis catus) and a
      bobcat (Lynx rufus). We also conducted a computational fluid dynamics simulation
      of nasal airflow in the bobcat to explore the relationship between epithelial
      distribution and airflow patterns. The results showed that a substantial amount
      of respiratory airflow passes over the anterior fronto-ethmoturbinals, and that
      contrary to what has been observed in caniform carnivorans, much of the anterior
      ethmoturbinals are covered by non-sensory epithelium. This confirms that in short
      snouted felids, portions of the fronto-ethmoturbinals have been recruited for
      respiration, and that estimates of olfactory epithelial coverage based purely on
      fronto-ethmoturbinal surface area will be exaggerated. The correlation between
      the shape of the anterior fronto-ethmoturbinals and the direction of respiratory
      airflow suggests that in short-snouted species, CT data alone are useful in
      assessing airflow patterns and epithelium distribution on the turbinals.

PMID- 27045094
TI  - Echo-acoustic flow affects flight in bats.
AB  - Flying animals need to react fast to rapid changes in their environment. Visually
      guided animals use optic flow, generated by their movement through structured
      environments. Nocturnal bats cannot make use of optic flow, but rely mostly on
      echolocation. Here, we show that bats exploit echo-acoustic flow to negotiate
      flight through narrow passages. Specifically, bats' flight between lateral
      structures is significantly affected by the echo-acoustic salience of those
      structures, independent of their physical distance. This is true even though
      echolocation, unlike vision, provides explicit distance cues. Moreover, the bats
      reduced the echolocation sound levels in stronger flow, probably to compensate
      for the increased summary target strength of the lateral reflectors. However,
      bats did not reduce flight velocity under stronger echo-acoustic flow. Our
      results demonstrate that sensory flow is a ubiquitous principle for flight
      guidance, independent of the fundamentally different peripheral representation of
      flow across the senses of vision and echolocation.

PMID- 27045095
TI  - Effect of magnetic pulses on Caribbean spiny lobsters: implications for
      magnetoreception.
AB  - The Caribbean spiny lobster, Panulirus argus, is a migratory crustacean that uses
      Earth's magnetic field as a navigational cue, but how these lobsters detect
      magnetic fields is not known. Magnetic material thought to be magnetite has
      previously been detected in spiny lobsters, but its role in magnetoreception, if
      any, remains unclear. As a first step toward investigating whether lobsters might
      have magnetite-based magnetoreceptors, we subjected lobsters to strong, pulsed
      magnetic fields capable of reversing the magnetic dipole moment of biogenic
      magnetite crystals. Lobsters were subjected to a single pulse directed from
      posterior to anterior and either: (1) parallel to the horizontal component of the
      geomagnetic field (i.e. toward magnetic north); or (2) antiparallel to the
      horizontal field (i.e. toward magnetic south). An additional control group was
      handled but not subjected to a magnetic pulse. After treatment, each lobster was
      tethered in a water-filled arena located within 200 m of the capture location and
      allowed to walk in any direction. Control lobsters walked in seemingly random
      directions and were not significantly oriented as a group. In contrast, the two
      groups exposed to pulsed fields were significantly oriented in approximately
      opposite directions. Lobsters subjected to a magnetic pulse applied parallel to
      the geomagnetic horizontal component walked westward; those subjected to a pulse
      directed antiparallel to the geomagnetic horizontal component oriented
      approximately northeast. The finding that a magnetic pulse alters subsequent
      orientation behavior is consistent with the hypothesis that magnetoreception in
      spiny lobsters is based at least partly on magnetite-based magnetoreceptors.

PMID- 27045096
TI  - Haematophagy is costly: respiratory patterns and metabolism during feeding in
      Rhodnius prolixus.
AB  - Feeding on the blood of vertebrates is a risky task for haematophagous insects
      and it can be reasonably assumed that it should also be costly in terms of
      energetic expenditure. Blood circulates inside vessels and it must be pumped
      through narrow tubular stylets to be ingested. We analysed the respiratory
      pattern and the energetic cost of taking a blood meal in Rhodnius prolixus using
      flow-through and stop-flow respirometry to measure carbon dioxide emission,
      oxygen consumption and water loss before and during feeding. We observed an
      increase of up to 17-fold in the metabolic rate during feeding and a change in
      the respiratory pattern, which switched from a discontinuous cyclic pattern
      during resting to a continuous pattern when the insects started to feed,
      remaining in this condition unchanged for several hours. The energetic cost of
      taking a meal was significantly higher when bugs fed on a living host, compared
      with feeding on an artificial feeder. No differences were observed between
      feeding on blood or on saline solution in vitro, revealing that the substrate for
      feeding (vessels versus membrane) and not the nature of the fluid was responsible
      for such a difference in the energetic cost. Water loss significantly increased
      during feeding, but did not vary with feeding method or type of food. The mean
      respiratory quotient in resting bugs was 0.83, decreasing during feeding to 0.52.
      These data constitute the first metabolic measures of an insect during blood
      feeding and provide the first insights into the energetic expenditure associated
      with haematophagy.

PMID- 27045097
TI  - By land or by sea: a modified C-start motor pattern drives the terrestrial tail
      flip.
AB  - Aquatic C-start escape responses in teleost fishes are driven by a well-studied
      network of reticulospinal neurons that produce a motor pattern of simultaneous
      contraction of axial muscle on the side of the body opposite the threatening
      stimulus, bending the fish into the characteristic C shape, followed by a
      traveling wave of muscle contraction on the contralateral side that moves the
      fish away from the threat. Superficially, the kinematics of the terrestrial tail
      flip resemble the C-start, with the anterior body rolling up and over the tail
      into a tight C shape, followed by straightening as the fish launches off of the
      caudal peduncle into ballistic flight. We asked whether similar motor control is
      used for both behaviors in the amphibious mangrove rivulus, Kryptolebias
      marmoratus Fine-wire bipolar electrodes were percutaneously inserted into
      repeatable paired axial locations in five individual fish. Electromyograms
      synchronized with high-speed video were made of aquatic C-starts, immediately
      followed by terrestrial tail-flips. Tail-flips took longer to complete than
      aquatic escapes; correspondingly, muscles were activated for longer durations on
      land. In the tail-flip, activity was seen in contralateral posterior axial muscle
      for an extended period of time during the formation of the C shape, likely to
      press the caudal peduncle against the ground in preparation for launch. Tail
      flips thus appear to be produced by modification of the motor pattern driving the
      aquatic C-start, with differences consistent with the additional requirement of
      overcoming gravity.

PMID- 27045098
TI  - Whiteflies stabilize their take-off with closed wings.
AB  - The transition from ground to air in flying animals is often assisted by the legs
      pushing against the ground as the wings start to flap. Here, we show that when
      tiny whiteflies (Bemisia tabaci, body length ca. 1 mm) perform take-off jumps
      with closed wings, the abrupt push against the ground sends the insect into the
      air rotating forward in the sagittal (pitch) plane. However, in the air, B.
      tabaci can recover from this rotation remarkably fast (less than 11 ms), even
      before spreading its wings and flapping. The timing of body rotation in air, a
      simplified biomechanical model and take-off in insects with removed wings all
      suggest that the wings, resting backwards alongside the body, stabilize motion
      through air to prevent somersaulting. The increased aerodynamic force at the
      posterior tip of the body results in a pitching moment that stops body rotation.
      Wing deployment increases the pitching moment further, returning the body to a
      suitable angle for flight. This inherent stabilizing mechanism is made possible
      by the wing shape and size, in which half of the wing area is located behind the
      posterior tip of the abdomen.

PMID- 27045099
TI  - The C-terminal motif of SiAGO1b is required for the regulation of growth,
      development and stress responses in foxtail millet (Setaria italica (L.) P.
      Beauv).
AB  - Foxtail millet (Setaria italica (L.) P. Beauv), which belongs to the Panicoideae
      tribe of the Poaceae, is an important grain crop widely grown in Northern China
      and India. It is currently developing into a novel model species for functional
      genomics of the Panicoideae as a result of its fully available reference genome
      sequence, small diploid genome (2n=18, ~510Mb), short life cycle, small stature
      and prolific seed production. Argonaute 1 (AGO1), belonging to the argonaute
      (AGO) protein family, recruits small RNAs and regulates plant growth and
      development. Here, we characterized an AGO1 mutant (siago1b) in foxtail millet,
      which was induced by ethyl methanesulfonate treatment. The mutant exhibited
      pleiotropic developmental defects, including dwarfing stem, narrow and rolled
      leaves, smaller panicles and lower rates of seed setting. Map-based cloning
      analysis demonstrated that these phenotypic variations were attributed to a C-A
      transversion, and a 7-bp deletion in the C-terminus of the SiAGO1b gene in
      siago1b Yeast two-hybrid assays and BiFC experiments revealed that the mutated
      region was an essential functional motif for the interaction between SiAGO1b and
      SiHYL1. Furthermore, 1598 differentially expressed genes were detected via RNA
      seq-based comparison of SiAGO1b and wild-type plants, which revealed that SiAGO1b
      mutation influenced multiple biological processes, including energy metabolism,
      cell growth, programmed death and abiotic stress responses in foxtail millet.
      This study may provide a better understanding of the mechanisms by which SiAGO1b
      regulates the growth and development of crops.

PMID- 27045101
TI  - Rociletinib: has the TIGER lost a few of its stripes?

PMID- 27045100
TI  - Genetics as a molecular window into recovery, its treatment, and stress responses
      after stroke.
AB  - Stroke remains a major source of adult disability in the USA and worldwide. Most
      patients show some recovery during the weeks to months following a stroke, but
      this is generally incomplete. An emerging branch of therapeutics targets the
      processes underlying this behavioral recovery from stroke toward the goal of
      reducing long-term disability. A key factor hampering these efforts is the very
      large degree of variability between stroke survivors. Available data suggest that
      genetic differences could explain an important fraction of the differences
      between subjects. The current review considers this from several angles,
      including genetic differences in relation to drugs that promote recovery. Genetic
      factors related to physiological and psychological stress responses may also be
      critically important to understanding recovery after stroke and its treatment.
      The studies reviewed provide insights into recovery and suggest directions for
      further research to improve clinical decision-making in this setting. Genetic
      differences between patients might be used to help clinical trials select
      specific patient subgroups, on a biological basis, in order to sharpen the
      precision with which new treatments are evaluated. Pharmacogenomic factors might
      also provide insights into inter-subject differences in treatment side effects
      for pharmacological prescriptions, and behavioral interventions, and others.
      These efforts must be conducted with the strictest ethical standards given the
      highly sensitive nature of genetic data. Understanding the effect of selected
      genetic measures could improve a clinician's ability to predict the risk and
      efficacy of a restorative therapy and to make maximally informed decisions, and
      in so doing, facilitate individual patient care.

PMID- 27045102
TI  - Utility of a molecular prescreening program in advanced colorectal cancer for
      enrollment on biomarker-selected clinical trials.
AB  - BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective
      clinical trials is an active area of investigation, but the factors that
      determine clinical trial enrollment following a molecular prescreening program
      have not been assessed. PATIENTS AND METHODS: Patients with 5-fluorouracil
      refractory metastatic colorectal cancer at the MD Anderson Cancer Center were
      offered screening in the Assessment of Targeted Therapies Against Colorectal
      Cancer (ATTACC) program to identify eligibility for companion phase I or II
      clinical trials with a therapy targeted to an aberration detected in the patient,
      based on testing by immunohistochemistry, targeted gene sequencing panels, and
      CpG island methylation phenotype assays. RESULTS: Between August 2010 and
      December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and
      157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on
      nonbiomarker selected). Of the 458 patients with a biomarker result, enrollment
      on biomarker-selected clinical trials was ninefold higher for predefined ATTACC
      companion clinical trials as opposed to nonpredefined biomarker-selected clinical
      trials, 17.9% versus 2%, P < 0.001. Factors that correlated positively with trial
      enrollment in multivariate analysis were higher performance status, older age,
      lack of standard of care therapy, established patient at MD Anderson, and the
      presence of an eligible biomarker for an ATTACC-companion study. Early molecular
      screening did result in a higher rate of patients with remaining standard of care
      therapy enrolling on ATTACC-companion clinical trials, 45.1%, in contrast to
      nonpredefined clinical trials, 22.7%; odds ratio 3.1, P = 0.002. CONCLUSIONS:
      Though early molecular prescreening for predefined clinical trials resulted in an
      increase rate of trial enrollment of nonrefractory patients, the majority of
      patients enrolled on clinical trials were refractory to standard of care therapy.
      Within molecular prescreening programs, tailoring screening for preidentified and
      open clinical trials, temporally linking screening to treatment and optimizing
      both patient and physician engagement are efforts likely to improve enrollment on
      biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number
      is NCT01196130.

PMID- 27045103
TI  - Withaferin A induces heme oxygenase (HO-1) expression in endothelial cells via
      activation of the Keap1/Nrf2 pathway.
AB  - Withaferin A (WA), a natural phytochemical derived from the plant Withania
      somnifera, is a well-studied bioactive compound exerting a broad spectrum of
      health promoting effects. To gain better insight in the potential therapeutic
      capacity of WA, we evaluated the transcriptional effects of WA on primary human
      umbilical vein endothelial cells (HUVECs) and an endothelial cell line
      (EA.hy926). RNA microarray analysis of WA treated HUVEC cells demonstrated
      increased expression of the antioxidant gene heme oxygenase (HO-1).
      Transcriptional regulation of this gene is strongly dependent on the
      transcription factor NF-E2-related factor 2 (Nrf2), which senses chemical changes
      in the cell and coordinates transcriptional responses to maintain chemical
      homeostasis via expression of antioxidant genes and cytoprotective Phase II
      detoxifying enzymes. Under normal conditions, Nrf2 is kept in the cytoplasm by
      Kelch-like ECH-associated protein 1 (Keap1), an adaptor protein controlling the
      half-life of Nrf2 via constant proteasomal degradation. In this study we
      demonstrate that WA time- and concentration-dependently induces HO-1 expression
      in endothelial cells via upregulation and increased nuclear translocation of
      Nrf2. According to the crucial negative regulatory role of Keap1 in Nrf2
      expression levels, a direct interaction of WA with Keap1 could be demonstrated.
      In vitro and in silico evaluations suggest that specific cysteine residues in
      Keap1 might be involved in the interaction with WA.

PMID- 27045104
TI  - Need for consensus guidelines to standardise the assessment of germinal centres
      and other histopathological parameters in salivary gland tissue of patients with
      primary Sjogren's syndrome.

PMID- 27045105
TI  - Response to: 'Evidence for treating rheumatoid arthritis to target: results of a
      systematic literature search update' by Goswami et al.

PMID- 27045106
TI  - Platelets in rheumatoid arthritis: exploring the anti-inflammatory and
      antithrombotic potential of TNF inhibitors.

PMID- 27045107
TI  - Complex Regulation Pattern of IRF3 Activation Revealed by a Novel Dimerization
      Reporter System.
AB  - Induction of type I IFN (IFN-I) is essential for host antiviral immune responses.
      However, IFN-I also plays divergent roles in antibacterial immunity, persistent
      viral infections, autoimmune diseases, and tumorigenesis. IFN regulatory factor 3
      (IRF3) is the master transcription factor that controls IFN-I production via
      phosphorylation-dependent dimerization in most cell types in response to viral
      infections and various innate stimuli by pathogen-associated molecular patterns
      (PAMPs). To monitor the dynamic process of IRF3 activation, we developed a novel
      IRF3 dimerization reporter based on bimolecular luminescence complementation
      (BiLC) techniques, termed the IRF3-BiLC reporter. Robust induction of luciferase
      activity of the IRF3-BiLC reporter was observed upon viral infection and PAMP
      stimulation with a broad dynamic range. Knockout of TANK-binding kinase 1, the
      critical upstream kinase of IRF3, as well as the mutation of serine 386, the
      essential phosphorylation site of IRF3, completely abolished the luciferase
      activity of IRF3-BiLC reporter, confirming the authenticity of IRF3 activation.
      Taken together, these results demonstrated that the IRF3-BiLC reporter is a
      highly specific, reliable, and sensitive system to measure IRF3 activity. Using
      this reporter system, we further observed that the temporal pattern and magnitude
      of IRF3 activation induced by various PAMPs are highly complex with distinct cell
      type-specific characteristics, and IRF3 dimerization is a direct regulatory node
      for IFN-alpha/beta receptor-mediated feed-forward regulation and crosstalk with
      other pathways. Therefore, the IRF3-BiLC reporter has multiple potential
      applications, including mechanistic studies as well as the identification of
      novel compounds that can modulate IRF3 activation.

PMID- 27045108
TI  - Synthetic Biology Reveals the Uniqueness of the RIP Kinase Domain.
AB  - The RIP kinases (RIPKs) play an essential role in inflammatory signaling and
      inflammatory cell death. However, the function of their kinase activity has been
      enigmatic, and only recently has kinase domain activity been shown to be crucial
      for their signal transduction capacity. Despite this uncertainty, the RIPKs have
      been the subject of intense pharmaceutical development with a number of compounds
      currently in preclinical testing. In this work, we seek to determine the
      functional redundancy between the kinase domains of the four major RIPK family
      members. We find that although RIPK1, RIPK2, and RIPK4 are similar in that they
      can all activate NF-kappaB and induce NF-kappaB essential modulator
      ubiquitination, only RIPK2 is a dual-specificity kinase. Domain swapping
      experiments showed that the RIPK4 kinase domain could be converted to a dual
      specificity kinase and is essentially indistinct from RIPK2 in biochemical and
      molecular activity. Surprisingly, however, replacement of RIPK2's kinase domain
      with RIPK4's did not complement a nucleotide-binding oligomerization domain 2
      signaling or gene expression induction defect in RIPK2(-/-) macrophages. These
      findings suggest that RIPK2's kinase domain is functionally unique compared with
      other RIPK family members and that pharmacologic targeting of RIPK2 can be
      separated from the other RIPKs.

PMID- 27045109
TI  - The Receptor for Advanced Glycation End Products Activates the AIM2 Inflammasome
      in Acute Pancreatitis.
AB  - Severe acute pancreatitis (AP) is responsible for significant human morbidity and
      mortality worldwide. Currently, no specific treatments for AP exist, primarily
      due to the lack of a mechanistic understanding of sterile inflammation and the
      resultant multisystem organ dysfunction, the pathologic response of AP linked to
      early death. In this study, we demonstrate that the class III major
      histocompatibility region III receptor for advanced glycation end products (RAGE)
      contributes to AP by modulating inflammasome activation in macrophages. RAGE
      mediated nucleosome-induced absent in melanoma 2 (but not NLRP3) inflammasome
      activation by modulating dsRNA-dependent protein kinase phosphorylation in
      macrophages. Pharmacological and genetic inhibition of the RAGE-dsRNA-dependent
      protein kinase pathway attenuated the release of inflammasome-dependent exosomal
      leaderless cytokines (e.g., IL-1beta and high-mobility group box 1) in vitro.
      RAGE or absent in melanoma 2 depletion in mice limited tissue injury, reduced
      systemic inflammation, and protected against AP induced by l-arginine or cerulein
      in experimental animal models. These findings define a novel role for RAGE in the
      propagation of the innate immune response with activation of the nucleosome
      mediated inflammasome and will help guide future development of therapeutic
      strategies to treat AP.

PMID- 27045111
TI  - In Reference to "Partial Epiglottoplasty for Pharyngeal Dysphagia due to Cervical
      Spine Pathology".

PMID- 27045112
TI  - Authors' Response to Letter: "In Reference to 'Partial Epiglottoplasty for
      Pharyngeal Dysphagia due to Cervical Spine Pathology'".

PMID- 27045113
TI  - A Revision in Evaluating the Results of Intratympanic Otoprotective Injections
      against Cisplatin-Induced Ototoxicity.

PMID- 27045114
TI  - Response to "A Revision in Evaluating the Results of Intratympanic Otoprotective
      Injections against Cisplatin-Induced Ototoxicity".

PMID- 27045115
TI  - Astrocytes contribute to the effects of etomidate on synaptic transmission in rat
      primary somatosensory cortex.
AB  - Little is known about the mechanisms of unconsciousness induced by general
      anesthetics. Previous studies have shown that the primary somatosensory cortex
      (S1) is a sensitive region to a variety of intravenous general anesthetics.
      Etomidate is a widely used intravenous anesthetic that can influence synaptic
      transmission. Recently, there are some evidences suggesting that astrocytes, a
      type of glia cell, also contribute to information transmission in the brain, and
      modulate synaptic function by releasing neuroactive substances. However, it is
      unknown whether astrocytes influence the effects of etomidate on information
      transmission in S1 pyramidal neurons. In the present study, the role of
      astrocytes in etomidate-induced unconsciousness was investigated by using the
      whole-cell patch clamp technique. We observed etomidate at clinically relevant
      concentrations inhibited the spontaneous postsynaptic currents (sPSCs) of rat S1
      pyramidal neurons in a concentration-dependent manner, and the EC50 value of
      etomidate for inhibiting sPSCs from the concentration-effect curve was 6.9MUM.
      Furthermore, in the presence of fluorocitrate, a glia-selective metabolism
      inhibitor that blocks the aconitase enzyme, both the amplitude and frequency of
      sPSCs in rat S1 pyramidal neurons were reduced, and the inhibitory effects of
      etomidate on sPSCs amplitude was strengthened without affecting the effects of
      etomidate on frequency. From these data, we deduce that etomidate suppresses
      synaptic activity via presynaptic and postsynaptic components. Furthermore,
      astrocytes participate in synaptic transmission and influence the effects of
      etomidate on postsynaptic receptors. This study provides new insight into the
      role of astrocytes in etomidate-induced unconsciousness.

PMID- 27045116
TI  - Automated multimodal segmentation of an abnormal breast mass in mammogram.
AB  - A lot of computer-aided diagnosis systems have been attempted to segment
      automatically breast mass from a mammogram and to classify the mass as benign and
      malignant quantitatively. This study aimed to develop an automated computer-aided
      diagnosis system to evaluate the disease with high accuracy using the proposed
      multimodal segmentation algorithm when compared to an abnormal breast mass region
      outlined in mammogram by radiologists of American College of Radiology as
      "standard." In this study, a total number of 150 mammograms were downloaded from
      the DDSM database for screening mammography. Based on the available diagnostic
      report, the studied data were classified as follows: (1) Group I: normal (n = 50,
      mean +/- SD age = 55 +/- 8 years), (2) Group II: benign breast cancer (n = 50,
      mean +/- SD age = 58 +/- 11 years), and (3) Group III: malignant breast cancer (n
      = 50, mean +/- SD age = 58+/-9 years). It was found that the proposed multimodal
      segmentation algorithm processed all the mammograms of different mass types,
      density, shapes, size, margin, calcification type, and distortion successfully,
      and it segmented the mass automatically with high accuracy. In this study, a
      computer-aided diagnosis system was developed to segment the breast mass
      automatically in a mammogram with high accuracy of 96%. The sensitivity and
      specificity of the system were found to be 94% and 97%, respectively, when
      compared to abnormal region outlined in mammogram by radiologists of American
      College of Radiology as standard. 

PMID- 27045117
TI  - Is the prevalence of hypertension in overweight children overestimated?
AB  - OBJECTIVES: The aim of this study is to explore different methods for screening
      and diagnosing hypertension-which definitions and criteria to use-in children and
      in addition to determine the prevalence of hypertension in Dutch overweight
      children. DESIGN: A cross-sectional study performed in the Dutch Child Health
      Care setting. SETTING: Four Child Health Care centres in different cities in the
      Netherlands. PARTICIPANTS: 969 overweight (including obese) and 438 non
      overweight children, median age 11.7 years (range 4.1-17.10), 49% boys. MAIN
      OUTCOME MEASURES: The main outcome was blood pressure, and the difference in
      prevalence of hypertension using different criteria for blood pressure
      interpretation: using the first blood pressure measurement, the mean of two
      measurements and the lowest of three measurements on two different occasions.
      RESULTS: Looking at the first measurement alone, 33% of overweight and 21% of non
      overweight children had hypertension. By comparing the mean of the first two
      measurements with reference values, 28% of overweight children and 16% of non
      overweight children had hypertension. Based on the lowest of three consecutive
      measurements, the prevalence decreased to 12% among overweight children and 5%
      among non-overweight children at visit one and at visit two 4% of overweight
      children still had hypertension. CONCLUSIONS: The prevalence of hypertension is
      highly dependent on the definitions and criteria used. We found a prevalence of
      4% in overweight children, which is considerably lower than suggested by recent
      literature (4%-33%). This discrepancy can be explained by our more strict
      definition of hypertension. However, to draw any conclusions on the prevalence,
      normal values using the same definition of hypertension should be established.
      Despite the low prevalence, we recommend measuring blood pressure in all
      overweight children in view of later cardiovascular morbidity and mortality.

PMID- 27045118
TI  - A prospective quality improvement study in the emergency department targeting
      paediatric sepsis.
AB  - OBJECTIVE: Quality improvement sepsis initiatives in the paediatric emergency
      department have been associated with improved processes, but an unclear effect on
      patient outcome. We aimed to evaluate and improve emergency department sepsis
      processes and track subsequent changes in patient outcome. STUDY DESIGN: A
      prospective observational cohort study in the emergency department of The Royal
      Children's Hospital, Melbourne. Participants were children aged 0-18 years of age
      meeting predefined criteria for the diagnosis of sepsis. The following
      shortcomings in management were identified and targeted in a sepsis intervention:
      administration of antibiotics and blood sampling for a venous gas at the time of
      intravenous cannulation, and rapid administration of all fluid resuscitation
      therapy. The primary outcome measure was hospital length of stay. RESULTS: 102
      patients were enrolled pre-intervention, 113 post-intervention. Median time from
      intravenous cannula insertion to antibiotic administration decreased from 55 min
      (IQR 27-90 min) pre-intervention to 19 min (IQR 10-32 min) post-intervention
      (p<=0.01). Venous blood gas at time of first intravenous cannula insertion was
      performed in 60% of patients pre-intervention vs 79% post-intervention (p<=0.01).
      Fluids were administered using manual push-pull or pressure-bag methods in 31% of
      patients pre-intervention and 84% of patients post-intervention (p<=0.01). Median
      hospital length of stay decreased from 96 h (IQR 64-198 h) pre-intervention to 80
      h (IQR 53-167 h) post-intervention (p=0.02). This effect persisted when corrected
      for unequally distributed confounders between pre-intervention and post
      intervention groups (uncorrected HR: 1.36, 95% CI 1.04 to 1.80, p=0.02; corrected
      HR: 1.34, 95% CI 1.01 to 1.80, p=0.04). CONCLUSIONS: Use of quality improvement
      methodologies to improve the management of paediatric sepsis in the emergency
      department was associated with a reduction in hospital length of stay.

PMID- 27045121
TI  - Clostridium Species Identification by 16S rRNA Pyrosequencing Metagenomics.

PMID- 27045122
TI  - Ebola Virus Persistence in Semen of Male Survivors.
AB  - We investigated the duration of Ebola virus (EBOV) RNA and infectious EBOV in
      semen specimens of 5 Ebola virus disease (EVD) survivors. EBOV RNA and infectious
      EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70
      days, respectively, after EVD onset.

PMID- 27045123
TI  - The Leading Seafood Cuisine of Anisakidosis in Japan.

PMID- 27045124
TI  - Reply to Cassir et al.

PMID- 27045125
TI  - How Will New Guidelines Affect CD4 Testing in Veterans With HIV?
AB  - BACKGROUND: Guidelines now recommend limited use of routine CD4 cell count
      testing in human immunodeficiency virus (HIV)-infected patients with successful
      viral control who are not immunocompromised. METHODS: CD4 and viral load tests
      for patients receiving HIV care from the US Department of Veterans Affairs during
      2009-2013 were evaluated to determine trends in CD4 testing frequency and the
      number, cost, and results of CD4 tests considered optional under the guidelines.
      RESULTS: There were 28 530 individuals with sufficient testing to be included. At
      the time of the last CD4 test, 19.8% of the cohort was eligible for optional
      monitoring and 15.6% for minimal monitoring. CD4 testing frequency declined by
      10.8% over 4 years, reducing the direct cost of testing by US$196 000 per year.
      Full implementation of new treatment guidelines could reduce CD4 testing a
      further 28.9%, an additional annual savings of US$600 000. CD4 tests conducted
      during periods of potentially reduced monitoring were rarely <200 cells/uL: 1.1%
      of the tests conducted when minimal monitoring was recommended and just 0.3% of
      tests conducted when optional monitoring was recommended were less than this
      value. CONCLUSIONS: Reduced CD4 monitoring of HIV-infected patients would result
      in modest cost savings and likely reduce patient anxiety, with little or no
      impact on the quality of care. Veterans Affairs has made substantial progress in
      reducing the frequency of optional CD4 testing, but further reductions may still
      be warranted.

PMID- 27045126
TI  - Influence of Minimum Inhibitory Concentration in Clinical Outcomes of
      Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the
      Breakpoint?
AB  - BACKGROUND: Daptomycin has become a front-line antibiotic for multidrug-resistant
      Enterococcus faecium bloodstream infections (BSIs). We previously showed that E.
      faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the
      higher end of susceptibility frequently harbor mutations associated with
      daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting
      daptomycin MICs of 3-4 ug/mL treated with daptomycin are more likely to have
      worse clinical outcomes than those exhibiting daptomycin MICs <=2 ug/mL. METHODS:
      We conducted a multicenter retrospective cohort study that included adult
      patients with E. faecium BSI for whom initial isolates, follow-up blood culture
      data, and daptomycin administration data were available. A central laboratory
      performed standardized daptomycin MIC testing for all isolates. The primary
      outcome was microbiologic failure, defined as clearance of bacteremia >=4 days
      after the index blood culture. The secondary outcome was all-cause in-hospital
      mortality. RESULTS: A total of 62 patients were included. Thirty-one patients
      were infected with isolates that exhibited daptomycin MICs of 3-4 ug/mL. Overall,
      34 patients had microbiologic failure and 25 died during hospitalization. In a
      multivariate logistic regression model, daptomycin MICs of 3-4 ug/mL (odds ratio
      [OR], 4.7 [1.37-16.12]; P = .014) and immunosuppression (OR, 5.32 [1.20-23.54]; P
      = .028) were significantly associated with microbiologic failure. Initial
      daptomycin dose of >=8 mg/kg was not significantly associated with evaluated
      outcomes. CONCLUSIONS: Daptomycin MICs of 3-4 ug/mL in the initial E. faecium
      blood isolate predicted microbiological failure of daptomycin therapy, suggesting
      that modification in the daptomycin breakpoint for enterococci should be
      considered.

PMID- 27045127
TI  - Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized,
      Clinical Efficacy Trial.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is the standard of care for patients with
      coronary heart disease. Despite considerable epidemiological evidence that high
      stress is associated with worse health outcomes, stress management training (SMT)
      is not included routinely as a component of CR. METHODS AND RESULTS: One hundred
      fifty-one outpatients with coronary heart disease who were 36 to 84 years of age
      were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with
      SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers
      obtained before and after treatment. A matched sample of CR-eligible patients who
      did not receive CR made up the no-CR comparison group. All participants were
      followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients
      randomized to CR+SMT exhibited greater reductions in composite stress levels
      compared with those randomized to CR alone (P=0.022), an effect that was driven
      primarily by improvements in anxiety, distress, and perceived stress. Both CR
      groups achieved significant, and comparable, improvements in coronary heart
      disease biomarkers. Participants in the CR+SMT group exhibited lower rates of
      clinical events compared with those in the CR-alone group (18% versus 33%; hazard
      ratio=0.49; 95% confidence interval, 0.25-0.95; P=0.035), and both CR groups had
      lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95%
      confidence interval, 0.27-0.71; P<0.001). CONCLUSIONS: CR enhanced by SMT
      produced significant reductions in stress and greater improvements in medical
      outcomes compared with standard CR. Our findings indicate that SMT may provide
      incremental benefit when combined with comprehensive CR and suggest that SMT
      should be incorporated routinely into CR. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00981253.

PMID- 27045128
TI  - Peripartum Cardiomyopathy.
AB  - Peripartum cardiomyopathy is a potentially life-threatening pregnancy-associated
      disease that typically arises in the peripartum period and is marked by left
      ventricular dysfunction and heart failure. The disease is relatively uncommon,
      but its incidence is rising. Women often recover cardiac function, but long
      lasting morbidity and mortality are not infrequent. Management of peripartum
      cardiomyopathy is largely limited to the same neurohormonal antagonists used in
      other forms of cardiomyopathy, and no proven disease-specific therapies exist
      yet. Research in the past decade has suggested that peripartum cardiomyopathy is
      caused by vascular dysfunction, triggered by late-gestational maternal hormones.
      Most recently, information has also indicated that many cases of peripartum
      cardiomyopathy have genetic underpinnings. We review here the known epidemiology,
      clinical presentation, and management of peripartum cardiomyopathy, as well as
      the current knowledge of the pathophysiology of the disease. 

PMID- 27045130
TI  - ECG Response: April 5, 2016.

PMID- 27045129
TI  - Report of the National Heart, Lung, and Blood Institute Working Group: An
      Integrated Network for Congenital Heart Disease Research.
AB  - The National Heart, Lung, and Blood Institute convened a working group in January
      2015 to explore issues related to an integrated data network for congenital heart
      disease research. The overall goal was to develop a common vision for how the
      rapidly increasing volumes of data captured across numerous sources can be
      managed, integrated, and analyzed to improve care and outcomes. This report
      summarizes the current landscape of congenital heart disease data, data
      integration methodologies used across other fields, key considerations for data
      integration models in congenital heart disease, and the short- and long-term
      vision and recommendations made by the working group. 

PMID- 27045131
TI  - Nonamyloidotic Light Chain Cardiomyopathy: The Arrhythmogenic Magnetic Resonance
      Pattern.

PMID- 27045132
TI  - Arnold M. Katz: 1932-2016.

PMID- 27045133
TI  - Heterozygous Familial Hypercholesterolemia.

PMID- 27045134
TI  - Letter by Tsuda Regarding Article, "Association Between Visceral and Subcutaneous
      Adipose Depots and Incident Cardiovascular Disease Risk Factors".

PMID- 27045135
TI  - Letter by Belge et al Regarding Article, "Mitomycin-Induced Pulmonary Veno
      Occlusive Disease: Evidence From Human Disease and Animal Models".

PMID- 27045136
TI  - Response to Letter Regarding Article, "Mitomycin-Induced Pulmonary Veno-Occlusive
      Disease: Evidence From Human Disease and Animal Model".

PMID- 27045137
TI  - Endothelial-to-Mesenchymal Transition: An Evolving Paradigm and a Promising
      Therapeutic Target in PAH.

PMID- 27045138
TI  - In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to
      Mesenchymal Transition via HMGA1 and Its Target Slug.
AB  - BACKGROUND: We previously reported high-throughput RNA sequencing analyses that
      identified heightened expression of the chromatin architectural factor High
      Mobility Group AT-hook 1 (HMGA1) in pulmonary arterial endothelial cells (PAECs)
      from patients who had idiopathic pulmonary arterial hypertension (PAH) in
      comparison with controls. Because HMGA1 promotes epithelial-to-mesenchymal
      transition in cancer, we hypothesized that increased HMGA1 could induce
      transition of PAECs to a smooth muscle (SM)-like mesenchymal phenotype
      (endothelial-to-mesenchymal transition), explaining both dysregulation of PAEC
      function and possible cellular contribution to the occlusive remodeling that
      characterizes advanced idiopathic PAH. METHODS AND RESULTS: We documented
      increased HMGA1 in PAECs cultured from idiopathic PAH versus donor control lungs.
      Confocal microscopy of lung explants localized the increase in HMGA1 consistently
      to pulmonary arterial endothelium, and identified many cells double-positive for
      HMGA1 and SM22alpha in occlusive and plexogenic lesions. Because decreased
      expression and function of bone morphogenetic protein receptor 2 (BMPR2) is
      observed in PAH, we reduced BMPR2 by small interfering RNA in control PAECs and
      documented an increase in HMGA1 protein. Consistent with transition of PAECs by
      HMGA1, we detected reduced platelet endothelial cell adhesion molecule 1 (CD31)
      and increased endothelial-to-mesenchymal transition markers, alphaSM actin,
      SM22alpha, calponin, phospho-vimentin, and Slug. The transition was associated
      with spindle SM-like morphology, and the increase in alphaSM actin was largely
      reversed by joint knockdown of BMPR2 and HMGA1 or Slug. Pulmonary endothelial
      cells from mice with endothelial cell-specific loss of Bmpr2 showed similar gene
      and protein changes. CONCLUSIONS: Increased HMGA1 in PAECs resulting from
      dysfunctional BMPR2 signaling can transition endothelium to SM-like cells
      associated with PAH.

PMID- 27045139
TI  - Evidence-Based Policy Making: Assessment of the American Heart Association's
      Strategic Policy Portfolio: A Policy Statement From the American Heart
      Association.
AB  - BACKGROUND: American Heart Association (AHA) public policy advocacy strategies
      are based on its Strategic Impact Goals. The writing group appraised the evidence
      behind AHA's policies to determine how well they address the association's 2020
      cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management
      indicators and identified research needed to fill gaps in policy and support
      further policy development. METHODS AND RESULTS: The AHA policy research
      department first identified current AHA policies specific to each CVH metric and
      CVD management indicator and the evidence underlying each policy. Writing group
      members then reviewed each policy and the related metrics and indicators. The
      results of each review were summarized, and topic-specific priorities and
      overarching themes for future policy research were proposed. There was generally
      close alignment between current AHA policies and the 2020 CVH metrics and CVD
      management indicators; however, certain specific policies still lack a robust
      evidence base. For CVH metrics, the distinction between policies for adults (age
      >=20 years) and children (<20 years) was often not considered, although policy
      approaches may differ importantly by age. Inclusion of all those <20 years of age
      as a single group also ignores important differences in policy needs for infants,
      children, adolescents, and young adults. For CVD management indicators, specific
      quantitative targets analogous to criteria for ideal, intermediate, and poor CVH
      are lacking but needed to assess progress toward the 2020 goal to reduce deaths
      from CVDs and stroke. New research in support of current policies needs to focus
      on the evaluation of their translation and implementation through expanded
      application of implementation science. Focused basic, clinical, and population
      research is required to expand and strengthen the evidence base for the
      development of new policies. Evaluation of the impact of targeted improvements in
      population health through strengthened surveillance of CVD and stroke events,
      determination of the cost-effectiveness of policy interventions, and measurement
      of the extent to which vulnerable populations are reached must be assessed for
      all policies. Additional attention should be paid to the social determinants of
      health outcomes. CONCLUSIONS: AHA's public policies are generally robust and well
      aligned with its 2020 CVH metrics and CVD indicators. Areas for further policy
      development to fill gaps, overarching research strategies, and topic-specific
      priority areas are proposed.

PMID- 27045140
TI  - Microshear Bond Strength of Tri-Calcium Silicate-based Cements to Different
      Restorative Materials.
AB  - PURPOSE: To evaluate the microshear bond strength of tri-calcium silicate-based
      materials to different restorative materials. MATERIALS AND METHODS: Thirty-five
      disks of TheraCal LC and Biodentine were fabricated using teflon molds according
      to manufacturers' instructions. Then the specimens were randomly divided into 7
      groups according to the materials applied: Fuji IX, Fuji II, Equia Fil, Vertise
      Flow, Filtek Bulk Fill Posterior Restorative, Filtek Z250 with Prime&Bond NT and
      with Clearfil SE Bond. All restorative materials were placed onto the disks using
      tygon tubes. Following a storage period, the specimens underwent microshear bond
      strength testing in a universal testing machine, and fracture modes were
      analyzed. Data were analyzed using one-way ANOVA and Tukey's post-hoc test.
      RESULTS: For all restorative materials, TheraCal LC showed significantly higher
      MUSBS values compared to Biodentine. GIC based materials showed the lowest MUSBS
      for TheraCal and Biodentine. For Biodentine, Filtek Z250 applied with Prime&Bond
      NT and Filtek Bulk Fill Posterior Restorative applied with Scotchbond Universal
      Adhesive exhibited the highest MUSBS, while Filtek Z250 applied with Clearfil SE
      Bond revealed the highest bond strength to TheraCal LC. CONCLUSION: For all
      restorative materials tested in this study, TheraCal LC showed higher MUSBS
      compared to Biodentine. For both TheraCal LC and Biodentine, the placement of GIC
      based materials prior to composite resin restorations might decrease the bond
      strength. Composite resins applied with self-etching adhesives increased the bond
      strength of TheraCal LC; however, for Biodentine, application of etch-and-rinse
      adhesives may improve the adhesion of composite resins.

PMID- 27045146
TI  - Use of X-ray Absorption Spectroscopy and Esterification to Investigate Cr(III)
      and Ni(II) Ligands in Alfalf a Biomass.
AB  - Previously performed studies have shown that alfalfa shoot biomass can bind an
      appreciable amount of nickel(II) and chromium(III) ions from aqueous solution.
      Direct and indirect approaches were applied to study the possible mechanis ms
      involved in metal binding by the alfalfa biomass. The direct approach involves
      investigations of the metal-bound alfal fa shoot biomass by X-ray absorption
      spectroscopic analysis (XANES and EXAFS). Results from these studies suggest that
      ni ckel(II) and chromium(III) binding mostly occurs through coordination with
      oxygen ligands. Indirect approaches consist of chemical modification of
      carboxylate groups that have been shown to play an important role in metal
      binding to the alfal fa biomass. An appreciable decrease in metal binding
      resulted after acidic methanol esterification of the biomass, indica ting that
      carboxyl groups are entailed in the metal binding by the alfalfa biomass. In
      addition, base hydrolysis of the a lfalfa biomass increased the binding of these
      metals, which further indicates that carboxyl groups play an important role in
      the binding of these metal ions from solution. Therefore, by combining two
      different techniques, our results indicate that carboxylate groups are the major
      ligands responsible for the binding of nickel(II) and chromium(III) by alfalfa
      bio mass. 

PMID- 27045147
TI  - [Phospholipids metabolism disorders in acute stroke].
AB  - The disturbances of cerebral circulation results in the violation of phospholipid
      metabolism. Activation of lipid peroxidation and protein kinase C and release of
      intracellular calcium leads to disruption of the homeostasis of
      phosphatidylcholine. The use of cytidine-5-diphosphocholine, which is used as an
      intermediate compound in the biosynthesis of phospholipids of the cell membrane,
      helps to stabilize cell membranes, and reduce the formation of free radicals.

PMID- 27045148
TI  - [International multicenter studies of treatment of severe traumatic brain
      injury].
AB  - Despite the introduction of new diagnostic and therapeutic methods, traumatic
      brain injury (TBI) remains one of the leading cause of death and disability
      worldwide. Standards and recommendations on conservative and surgical treatment
      of TBI patients should be based on concepts and methods with proven efficacy. The
      authors present a review of studies of the treatment and surgery of severe TBI:
      DECRA, RESCUEicp, STITCH(TRAUMA), CRASH, CRASH-2, CAPTAIN, NABIS: H ll, Eurotherm
      3235. Important recommendations of the international group IMPACT are considered.

PMID- 27045149
TI  - Response.

PMID- 27045150
TI  - Gun Violence in America: A Clarion Call to Action.

PMID- 27045151
TI  - Early Breast Cancer Screening for African- American Women: A Clarion Call to
      Arms.

PMID- 27045152
TI  - Cognitive Reserve and Physical Function in Older African-Americans.
AB  - This study examined the relationship between cognitive reserve and
      physicalfunction in older African-Americans. The concept of cognitive reserve
      postulates that aspects of life experience (e.g., education, occupational
      complexity, leisure activity, and socioeconomic status) may provide cognitive
      reserve, in theform of a set of skills or repertoires, that allow some people to
      cope better than others with illness and alter the clinical expression of decline
      in functional status. This study used a descriptive correlational design.
      Physicalfunction was assessed with the SF-36 (physicalfunction subscale). The
      mean scorefor the SF-36 PF subscale was 47 (SD = 10), indicating that the
      participants had good physical functioning. Physical function was associated with
      occupational complexity, educational attainment, and income. The study provides
      baseline data about the relationship between cognitive reserve and
      physicalfunction.

PMID- 27045153
TI  - The Effects of Symptoms on Quality of Life during Chemotherapy in African
      American Women with Breast Cancer.
AB  - Little is known about the effects of burdensome symptoms dur- ing chemotherapy
      treatment in African-American women. This study explored the symptom burden
      occurring during chemotherapy treatment and how these symptoms impacted
      functional well-being and quality of life (QOL). A sample of 30 African-American
      women with breast cancer (BC) completed a battery of questionnaires that were
      used to collect the data at baseline, midpoint, and at the completion of
      chemotherapy. There were significant differences in the severity of symptoms for
      worse pain, pain inteiference with activities of daily living (ADLs), present
      fatigue and history offatigue, present nausea and history of nausea and insomnia
      as well as lower intensity of QOL measures over the course of chemotherapy
      treatment. All symptoms had greater intensity at midpoint and completion than at
      baseline. Worst pain had a significant negative effect on functional well-being.
      Both pain and depression each had significant negative effects on QOL.

PMID- 27045154
TI  - Identifying Women at Risk for Hereditary Breast and Ovarian Cancer Syndrome
      Utilizing Breast Care Nurse Navigation at Mammography and Imaging Centers.
AB  - Approximately 5-10% of breast cancer cases appear in families at a higher rate
      and at an earlier onset than in the average population. Two known gene defects,
      BRCA1 and BRCA2, account for the majority of these hereditary related breast
      cancers. Additionally, BRCA1 and BRCA2 are related to the Hereditary Breast and
      Ovarian Cancer syndrome (HBOC), where risk for other related cancers are
      increased. Various health-care professional organizations provide guidelines that
      speak to the need for conducting risk assessments, but little research has been
      conducted focusing on the initial screening for this syndrome. This quality
      improvement project attempts to determine if Nurse Navigators can effectively
      perform the initial education and screening for HBOC syndrome within a
      mammography and women's breast imaging setting using a simplified patient history
      tool. E. M. Rodgers' Diffusion of Innovation model, a map of how new ideas and
      programs have become adopted and accepted, guided this project's development and
      implementation. Over the course of 8 weeks, 1,420 women seeking service at 3
      mammography and imaging sites were given a new risk assessment tool for HBOC.
      Additionally, the use of Nurse Navigation to identify women who may be at risk
      for HBOC was implemented. Two populations seeking service at the study sites were
      evaluated: (1) women obtaining breast screening/imaging services and (2) women
      receiving breast biopsy results. Patients identified as "at-risk" were defined by
      evidence-based practice guidelines from the National Comprehensive Cancer Network
      and were referred for further genetic evaluation by a genetic professional.
      During this initial implementation of the HBOC risk assessment program, low
      participation of screening/imaging patients requesting HBOC education and
      evaluation occurred (129 screening patients or 9%). High rates of positive biopsy
      patients (5 patients or 34.7%) werefound to be at risk for HBOC compared to
      similar studies. Identifying HBOC risk at the time of breast biopsy results gave
      the opportunity to impact the timing and kind of surgical management of patients
      at risk for this syndrome.The Commission on Cancer (CoC), an arm of the American
      College of Surgeons, provides practice guideline standards and accreditation for
      cancer programs. Patients will become more familiar with being assessed for HBOC
      and other hereditary cancers during their annual health-care visits and more
      identification of patients at riskfor HBOC should occur as new CoC 2012 standards
      requiring hereditary cancer risk assessments for a cancer program's certification
      are enacted.

PMID- 27045155
TI  - Influence of Type 1 Diabetes Mellitus on Women's Nutritional Beliefs and
      Lifestyle Choices for Themselves and Their Families.
AB  - The aim of this research was to examine the impact of type 1 diabetes on women's
      nutritional beliefs and their lifestyle choices both for themselves and for their
      families. The data sources used were the online databases of OVID, CINAHL,
      MEDLINE, PsyINFO, PsyARTICLE, ERIC, Health Source Nursing/Academic edition, and
      the Centers for Disease Control from January 2000 to 2012. The concentration of
      the search was to identify literature with the key words "nutrition,"
      "lifestyle," or "women with type 1 diabetes." The researchers found 28 data-based
      research articles that examined women with type 1 diabetes. The articles were
      individually scrutinized for relevance and limited to English language articles.
      Data concerning the nutritional beliefs, lifestyle choices, andfamily dynamics
      among women with DM1 were extracted. The research articles consisted of 19
      qualitative studies, 7 quantitative studies, and 2 theory-testing studies. The
      themefor the studies included, but was not limited to, birth size, eating
      disorders, complications of diabetes mellitus, theory testing, documentations of
      effectiveness, estimations of carbohydrates, weight, changes during pregnancy in
      women with type 1 diabetes mellitus, and their educational preferences. This
      integrative review described the effects of DM1 on women's nutritional belief and
      lifestyle choices. Results demonstrated the importance of education and follow
      ups; however, future studies are needed to identify factors that contribute to
      noncompliance and waysfor patients to comprehend the seriousness of complications
      that can arise from type 1 diabetes mellitus.

PMID- 27045156
TI  - Obesity in African-American Women--The Time Bomb is Ticking: An Urgent Call for
      Change.
AB  - The "time bomb is ticking" because there is an obesity crisis associated with
      higher rates of chronic diseases such as stroke, hypertension, type 2 diabetes,
      and some forms of cancer in African-American women compared to White women.
      African-American women incur higher medical costs from hospitalizations,
      decreased productivity in the work setting, lost wages, the needfor medical
      benefits and pharmacy-associated costs, and more time away from family than White
      women. Numerous factors, such as the socio-cultural context of eating, acceptance
      of a larger weight status, the emotionally liberating effects offood, and
      preference for highfat and high caloric, sugary-content, and sodium-laden food
      influences the obesity crisis in African-American women. The interplay of poverty
      and lower socioeconomic status, residential segregation, health literacy,
      availability of fast foods and scarce produce in local convenience food marts,
      physical inactivity, and conflicting messages from social media public service
      announcements (PSAs) and ads in national magazines affect the obesity crisis in
      African-American women. There is an urgent call for sustainable, community-driven
      health policy initiatives that improve access to healthy foods in lower-income,
      minority communities. Furthermore, African-American women are challenged to
      modify their health behaviors by preparing healthy meals for themselves and
      theirfamilies, and by engaging in physical activity.

PMID- 27045157
TI  - Perceptions of Physical Activity and Influences of Participation in Young African
      American Adolescent Girls.
AB  - The purpose of this study was to explore African-American adolescent girls'
      perceptions of physical activity participation, examine how physical activity is
      defined and identify the most preferred forms of physical activity. Qualitative
      focus group interviews of a convenience sample (N = 30; Mean age = 14.3 years)
      were used to identifyfactors that influence African-American girls' physical
      activity participation as well as to explore how physical activity is defined
      within this population. Four themes emerged: (a) benefits and motivation to
      engage in physical activity, (b) behaviors consistent with perceived physical
      activity, (c) most enjoyable physical activity/activities, and (d) barriers to
      physical activity. Physical activities that promoted normative adolescent
      development (i.e., autonomy) were perceived as most beneficial, desirable, and
      most likely to be sustained. Implications of these findings highlight the
      importance of the incorporation of socialization and peer engagement in physical
      activity programs designed for African-American adolescent girls.

PMID- 27045158
TI  - A Qualitative Study: African-American Girls' Perceptions of Why Physical Activity
      Declines in High School.
AB  - African-American adolescent girls are less physically active than any other U.S.
      racial/ethnic group. The school environment may contribute to physical inactivity
      in this group. The purpose of this study was to explore African-American girls'
      perceptions offactors that contribute to girls being less physically active in
      high school. Interpretative Phenomenological Analysis (IPA) was used to identify
      individual perceptions of girls regarding physical activity. This resulted in
      four themes: personal appearances, scheduling/timing of classes,
      environmental/facilities issues, and lack of variety of activities in PE classes.
      Thefindings from this study indicated that African-American adolescent girls did
      not feel the physical or social school environment encouraged or supported them
      to be physically active.

PMID- 27045159
TI  - Assessment of the Feasibility of Barber-Led Sexual Education for African-American
      Adolescent Males.
AB  - This study explored the feasibility of a sexual health promotion barbershop
      program in the African-American urban areas of a large mid-southern city. A cross
      sectional descriptive design was used with a random survey. The sample consisted
      of 56 barbers and adult community patrons of sample barbershops. A questionnaire
      assessed current barbershop topics, current opinions of barber reliability, and
      the desire for participation in a barber-led health promotion intervention.
      Barbers unanimously supported the needfor such a program and reported willingness
      to participate in training to provide evidence-based information to teens.
      Findings suggested that a barber-led health promotion program would be
      facilitated by the facts that barbers serve as mentors, barbers resemble father
      figures, and the level of barber-client trust is high. Barriers consisted
      offinancial constraints, time constraints, and lack of parental consent. Future
      studies should focus on program development, focusing on comprehensive health
      promotion activities in addition to sexual health.

PMID- 27045160
TI  - Nurses: Leading to Reduce Health Disparities in an Era of Healthcare Reform.
AB  - Persistent disparities in health status and outcomes for racial/ethnic minority
      populations are well documented. African-Americans are disproportionately
      impacted by a number of conditions including cancer, cardiovascular disease,
      diabetes, HIV/AIDS, and inadequate mental healthcare. The 2010 Affordable Care
      Act (ACA) contains provisions to reduce health disparities. These provisions aim
      to improve the quality of care, reduce costs, increase access to care, strengthen
      the health-care workforce, and make health coverage more obtainable. Thus, the
      objectives of this paper are to describe key elements outlined in the ACA aimed
      at reducing health disparities and identify implications for nurses to lead in
      the reduction of health-care disparities through practice, education, research,
      and advocacy. Nurses at all levels of practice and education are encouraged to
      intensify their advocacy and legislative efforts to help ensure that key ACA
      provisions are funded and implemented to improve the overall well-being of
      underserved communities.

PMID- 27045161
TI  - Race-Based Health Disparities and the Digital Divide: Implications for Nursing
      Practice.
AB  - Knowledge of the sources of race-based health disparities could improve nursing
      practice and education in minority underserved communities. This purpose of this
      paper was to consider if Black-nonBlack health disparities were at least in part
      explained by Black-nonBlack disparities in access to Internet-based health
      information. With data on the U.S. adult population from the 2012 General Social
      Survey, the parameters of a health production function in which computer usage as
      an input was estimated. It was found that while there are Black-nonBlack
      disparities in health, once computer usage was accounted for, Black-nonBlack
      health disparities disappeared. This suggests nursing and health interventions
      that improve Internet access for Black patients in underserved communities could
      improve the health of Black Americans and close the racial health disparities
      gap. These findings complement recent nursing researchfindings that suggest
      closing Black-nonBlack disparities in computer access, the "digital divide," can
      render nursing practice more effective in providing care to minority and
      underserved communities.

PMID- 27045162
TI  - How Oncology Nursing Research Impacts Healthcare Policy.

PMID- 27045163
TI  - Analytical solutions to dissolved contaminant plume evolution with source
      depletion during carbon dioxide storage.
AB  - Volatile contaminants may migrate with carbon dioxide (CO2) injection or leakage
      in subsurface formations, which leads to the risk of the CO2 storage and the
      ecological environment. This study aims to develop an analytical model that could
      predict the contaminant migration process induced by CO2 storage. The analytical
      model with two moving boundaries is obtained through the simplification of the
      fully coupled model for the CO2-aqueous phase -stagnant phase displacement
      system. The analytical solutions are confirmed and assessed through the
      comparison with the numerical simulations of the fully coupled model. Then, some
      key variables in the analytical solutions, including the critical time, the
      locations of the dual moving boundaries and the advance velocity, are discussed
      to present the characteristics of contaminant migration in the multi-phase
      displacement system. The results show that these key variables are determined by
      four dimensionless numbers, Pe, RD, Sh and RF, which represent the effects of the
      convection, the dispersion, the interphase mass transfer and the retention factor
      of contaminant, respectively. The proposed analytical solutions could be used for
      tracking the migration of the injected CO2 and the contaminants in subsurface
      formations, and also provide an analytical tool for other solute transport in
      multi-phase displacement system.

PMID- 27045164
TI  - Health-related quality of life during bosutinib (SKI-606) therapy in patients
      with advanced chronic myeloid leukemia after imatinib failure.
AB  - OBJECTIVES: The tyrosine kinase inhibitor (TKI) bosutinib has demonstrated
      activity in patients with advanced phase chronic myeloid leukemia (CML), but
      effects on health-related quality of life (HRQoL) remain unexplored. This study
      evaluated HRQoL in advanced CML patients receiving bosutinib in an ongoing phase
      2 study following resistance or intolerance to prior imatinib therapy. METHODS:
      This analysis included data from 76 accelerated-phase (AP) and 64 blast-phase
      (BP) patients resistant/intolerant to prior imatinib with or without prior
      exposure to other TKIs. Patient-reported HRQoL assessments completed at baseline;
      weeks 4, 8, and 12; every 12 weeks thereafter; and at treatment completion
      included the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu); general
      health status was assessed using the 5-item EuroQol (EQ-5D) instrument and a
      visual analog scale (VAS). RESULTS: HRQoL at baseline was somewhat worse in BP
      versus AP CML patients. There was a significant improvement in the mean FACT-Leu
      Total scale at weeks 24, 36, and 48 in AP CML patients and at weeks 4, 8, 12, 24,
      36, 48, and 96 in BP CML patients compared with baseline. EQ-5D Utility scores
      were stable throughout treatment in AP CML patients but significantly improved
      versus baseline in BP CML patients at weeks 4, 8, 12, and 36. Mean VAS scores
      were significantly improved at weeks 8, 36, and 48 in AP CML patients and at
      weeks 4, 8, 12, 24, 36, and 96 in BP CML patients. The lack of a comparison group
      limits attribution of improvements in HRQoL specifically to bosutinib treatment;
      potential bias due to non-ignorable dropout may limit the ability to generalize
      these findings to situations where durations of therapy exceed the 96-week follow
      up duration of the present study. CONCLUSION: These findings suggest that
      bosutinib therapy is associated with improved HRQoL in advanced phase CML
      patients. CLINICAL TRIAL REGISTRATION: NCT00261846.

PMID- 27045165
TI  - Cu(I)- or Ag(I)-Catalyzed Regio- and Stereocontrolled trans-Hydrofluorination of
      Ynamides.
AB  - With Et3N.3HF as the fluorinating reagent, a copper(I)- or silver(I)-catalyzed
      beta/alpha-site-regiocontrolled trans-hydrofluorination of alkynamides has been
      achieved, affording the corresponding fluoro enamides in moderate to nearly
      quantitative yields with high regio- and stereoselectivity, respectively. The
      reaction proceeds under mild reaction conditions and exhibits good functional
      group tolerance. Further, the deuterium-labeling experiment confirmed the
      existence of the alkenylcopper intermediate. 

PMID- 27045166
TI  - Genetic Diversity and Genome Wide Association Study of beta-Glucan Content in
      Tetraploid Wheat Grains.
AB  - Non-starch polysaccharides (NSPs) have many health benefits, including
      immunomodulatory activity, lowering serum cholesterol, a faecal bulking effect,
      enhanced absorption of certain minerals, prebiotic effects and the amelioration
      of type II diabetes. The principal components of the NSP in cereal grains are
      (1,3;1,4)-beta-glucans and arabinoxylans. Although (1,3;1,4)-beta-glucan
      (hereafter called beta-glucan) is not the most representative component of wheat
      cell walls, it is one of the most important types of soluble fibre in terms of
      its proven beneficial effects on human health. In the present work we explored
      the genetic variability of beta-glucan content in grains from a tetraploid wheat
      collection that had been genotyped with a 90k-iSelect array, and combined this
      data to carry out an association analysis. The beta-glucan content, expressed as
      a percentage w/w of grain dry weight, ranged from 0.18% to 0.89% across the
      collection. Our analysis identified seven genomic regions associated with beta
      glucan, located on chromosomes 1A, 2A (two), 2B, 5B and 7A (two), confirming the
      quantitative nature of this trait. Analysis of marker trait associations (MTAs)
      in syntenic regions of several grass species revealed putative candidate genes
      that might influence beta-glucan levels in the endosperm, possibly via their
      participation in carbon partitioning. These include the glycosyl hydrolases endo
      beta-(1,4)-glucanase (cellulase), beta-amylase, (1,4)-beta-xylan endohydrolase,
      xylanase inhibitor protein I, isoamylase and the glycosyl transferase starch
      synthase II. 

PMID- 27045167
TI  - Role of Multi-Parametric Magnetic Resonance Image and PIRADS Score in Patients
      with Prostate Cancer Eligible for Active Surveillance According PRIAS Criteria.
AB  - OBJECTIVE: To evaluate the prognostic role of multiparametric-MRI (mp-MRI) in
      patients with clinically localized prostate cancer (PCa) eligible for active
      surveillance (AS) according to Prostate Cancer Research International: Active
      Surveillance (PRIAS) criteria. PATIENTS AND METHODS: We analyzed prospectively 73
      patients with PCa and PRIAS criteria for low-risk disease. All patients fitted
      criteria for AS but optioned surgery treatment. The mp-MRI was performed to
      define the likelihood of malignancy according to the Prostate Imaging Reporting
      and Data System (PIRADS) score (1-5). Patients were divided in 2 groups: non
      visible cancer lesion on MRI (PIRADS 2-3) and visible cancer (PIRADS 4-5).
      Preoperative clinical data (age, body mass index, prostate specific antigen (PSA)
      level, positive core biopsy, PSA density (PSAD)) and definitive pathological
      findings (staging, upgrading, unfavorable disease) were compared between groups.
      PIRADS score was correlated with pathological data to evaluate the prognostic
      role of mp-MRI; and preoperative variables and definitive pathology (upgrading,
      upstaging and unfavorable disease) were also assessed. RESULTS: PSAD (p = 0.04)
      and pathological stage (p = 0.03) were significantly associated with the presence
      of visible disease. Visible disease was significantly associated with upstaging
      (p = 0.03). Correlation between PIRADS 5 and unfavorable disease was
      statistically significant (p = 0.02). The mp-MRI had adequate sensibility in
      detecting upstaging (92%), intermediate for upgrading (76%) and unfavorable
      disease (76%). Negative predictive value was higher for upstaging than for
      upgrading or unfavorable disease (96 vs. 68% and 64%). Multivariate logistic
      regression revealed that PIRADS 5 was a significant predictor of upstaging (p =
      0.05, OR 16.12) and unfavorable disease (p = 0.01, OR 6.53). CONCLUSION: A
      visible lesion on mp-MRI strongly predicts significant PCa in patients eligible
      for AS according to PRIAS criteria, based on upstaging and unfavorable disease.
      We believe that mp-MRI is an important tool and should be added to clinical
      selection criteria for AS.

PMID- 27045168
TI  - Quantification of Treatment Effect Modification on Both an Additive and
      Multiplicative Scale.
AB  - BACKGROUND: In both observational and randomized studies, associations with
      overall survival are by and large assessed on a multiplicative scale using the
      Cox model. However, clinicians and clinical researchers have an ardent interest
      in assessing absolute benefit associated with treatments. In older patients, some
      studies have reported lower relative treatment effect, which might translate into
      similar or even greater absolute treatment effect given their high baseline
      hazard for clinical events. METHODS: The effect of treatment and the effect
      modification of treatment were respectively assessed using a multiplicative and
      an additive hazard model in an analysis adjusted for propensity score in the
      context of coronary surgery. RESULTS: The multiplicative model yielded a lower
      relative hazard reduction with bilateral internal thoracic artery grafting in
      older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p
      = 0.05) whereas the additive model reported a similar absolute hazard reduction
      with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p =
      0.61). The number needed to treat derived from the propensity score-adjusted
      multiplicative model was remarkably similar at the end of the follow-up in
      patients aged < = 60 and in patients >70. CONCLUSIONS: The present example
      demonstrates that a lower treatment effect in older patients on a relative scale
      can conversely translate into a similar treatment effect on an additive scale due
      to large baseline hazard differences. Importantly, absolute risk reduction,
      either crude or adjusted, can be calculated from multiplicative survival models.
      We advocate for a wider use of the absolute scale, especially using additive
      hazard models, to assess treatment effect and treatment effect modification.

PMID- 27045169
TI  - Alleged Approach-Avoidance Conflict for Food Stimuli in Binge Eating Disorder.
AB  - OBJECTIVE: Food stimuli are omnipresent and naturally primary reinforcing
      stimuli. One explanation for the intake of high amounts of food in binge eating
      disorder (BED) is a deviant valuation process. Valuation of food stimuli is
      supposed to influence approach or avoidance behaviour towards food. Focusing on
      self-reported and indirect (facial electromyography) valuation process,
      motivational aspects in the processing of food stimuli were investigated.
      METHODS: We compared an overweight sample with BED (BED+) with an overweight
      sample without BED (BED-) and with normal weight controls (NWC) regarding their
      self-reported and indirect (via facial electromyography) valuation of food versus
      non-food stimuli. RESULTS: Regarding the self-reported valuation, the BED+ sample
      showed a significantly stronger food-bias compared to the BED- sample, as food
      stimuli were rated as significantly more positive than the non-food stimuli in
      the BED+ sample. This self-reported valuation pattern could not be displayed in
      the indirect valuation. Food stimuli evoked negative indirect valuation in all
      groups. The BED+ sample showed the plainest approach-avoidance conflict marked by
      a diverging self-reported (positive) and indirect (negative) valuation of food
      stimuli. CONCLUSIONS: BED+ showed a deviant self-reported valuation of food as
      compared to BED-. The valuation process of the BED+ sample seems to be
      characterized by a motivational ambivalence. This ambivalence should be subject
      of further studies and may be of potential use for therapeutic interventions.

PMID- 27045171
TI  - Exploring the Utility of a School-Age Narrative Microstructure Index: Proportion
      of Restricted Utterances.
AB  - PURPOSE: This research attempted to replicate Hoffman's 2009 finding that the
      proportion of narrative utterances with semantic or syntactic errors (i.e., >=
      14% "restricted utterances") can differentiate school-age children with typical
      development from those with language impairment with a sensitivity of 83% and
      specificity of 88%. METHOD: Methods similar to Hoffman (2009) were used to
      evaluate an existing set of narratives from 16 age-matched pairs of 8- to 9-year
      old children, half with known language impairment. Transcripts were segmented
      into T-units; a code of [RESTRICTED] was assigned to any utterance with semantic
      or syntactic errors. RESULTS: A Welch's t test for independent samples revealed a
      statistically significant difference in the mean proportion of restricted
      utterances between the two groups after accommodation for an outlier with typical
      development. A cutoff of >= 14% restricted utterances replicated Hoffman's (2009)
      sensitivity but not specificity. Post hoc analysis of specific error types found
      sensitivity and specificity rates similar to Hoffman's as well as a significant
      difference in means when using a proportion of sentence-internal morphosyntactic
      errors. CONCLUSION: Results support further exploration of utterance-level error
      coding for diagnostic purposes and future development of this approach to meet
      clinical assessment needs.

PMID- 27045170
TI  - Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion
      Protein Confers Consistent and Improved Protection against Brugia malayi
      Infection.
AB  - BACKGROUND: The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to
      Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best
      candidates for the development of an O. volvulus vaccine. The B. malayi gerbil
      model was used to confirm the efficacy of these Ov vaccine candidates on adult
      worms and to determine whether their combination is more efficacious. METHODOLOGY
      AND PRINCIPLE FINDINGS: Vaccine efficacy of recombinant Bm-103 and Bm-RAL-2
      administered individually, concurrently or as a fusion protein were tested in
      gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm
      reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi),
      respectively, and vaccination with Bm-RAL-2 resulted in worm reductions of 42%,
      22% and 46% on 42, 120 and 150 dpi, respectively. Vaccination with a fusion
      protein comprised of Bm-103 and Bm-RAL-2 resulted in improved efficacy with
      significant reduction of worm burden of 51% and 49% at 90 dpi, as did the
      concurrent vaccination with Bm-103 and Bm-RAL-2, with worm reduction of 61% and
      56% at 90 dpi. Vaccination with Bm-103 and Bm-RAL-2 as a fusion protein or
      concurrently not only induced a significant worm reduction of 61% and 42%,
      respectively, at 150 dpi, but also significantly reduced the fecundity of female
      worms as determined by embryograms. Elevated levels of antigen-specific IgG were
      observed in all vaccinated gerbils. Serum from gerbils vaccinated with Bm-103 and
      Bm-RAL-2 individually, concurrently or as a fusion protein killed third stage
      larvae in vitro when combined with peritoneal exudate cells. CONCLUSION: Although
      vaccination with Bm-103 and Bm-RAL-2 individually conferred protection against B.
      malayi infection in gerbils, a more consistent and enhanced protection was
      induced by vaccination with Bm-103 and Bm-RAL-2 fusion protein and when they were
      used concurrently. Further characterization and optimization of these filarial
      vaccines are warranted.

PMID- 27045172
TI  - Beware of Rim-Enhancing Lesions: A Rare Case of Multiple Scedosporium apiospermum
      and Vancomycin-Resistant Enterococcus faecium Intra-Cranial Abscesses.
AB  - BACKGROUND: The aim of this submission is to demonstrate the need for broad
      antimicrobial therapy, including empiric anti-fungal therapy, if rim-enhancing
      lesions are noted on cerebral imaging. METHODS: A retrospective microbiological
      and radiologic review of the management of a rare case of multiple Scedosporium
      apiospermum and vancomycin-resistant Enterococcus faecium intra-cranial abscesses
      in an immunocompromised patient was performed. A manual chart review assessing
      clinical and epidemiologic characteristics was completed including procedures and
      operative notes, use of invasive devices, biochemical and haematological blood
      test results, antimicrobial agents received, and documentation of a travel
      history. RESULTS: Antimicrobial therapy combined with source control, typically
      surgical drainage, is considered the gold standard management of an intra-cranial
      abscess. Fungal abscesses produce rim-enhancing lesions, and where this
      radiographic feature is identified, evidence suggests that anti-fungal agents
      should be added. Antimicrobial therapy with linezolid and voriconazole failed,
      and the patient died. There was extensive disease progression evident on serial
      imaging despite therapy. A definitive surgical drainage procedure could not be
      performed. CONCLUSIONS: Interval imaging assisted with the management of this
      challenging case. A low index of clinical suspicion for fungal intra-cerebral
      abscesses is necessary when treating immunosuppressed patients.

PMID- 27045174
TI  - Absolute structure determination using CRYSTALS.
AB  - A study of post-refinement absolute structure determination using previously
      published data was carried out using the CRYSTALS software package. We show that
      absolute structure determination may be carried out optimally using the analyses
      available in CRYSTALS, and that it is not necessary to have the separate
      procedures absolute structure determination and no interest in absolute structure
      as proposed by Flack [Chimia (2014), 68, 26-30]. 

PMID- 27045173
TI  - Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium
      Channels.
AB  - Few gating-modifier toxins have been reported to target low-voltage-activated
      (LVA) calcium channels, and the structural basis of toxin sensitivity remains
      incompletely understood. Studies of voltage-gated potassium (Kv) channels have
      identified the S3b-S4 "paddle motif," which moves at the protein-lipid interface
      to drive channel opening, as the target for these amphipathic neurotoxins.
      Voltage-gated calcium (Cav) channels contain four homologous voltage sensor
      domains, suggesting multiple toxin binding sites. We show here that the S3-S4
      segments within Cav3.1 can be transplanted into Kv2.1 to examine their individual
      contributions to voltage sensing and pharmacology. With these results, we now
      have a more complete picture of the conserved nature of the paddle motif in all
      three major voltage-gated ion channel types (Kv, Nav, and Cav). When screened
      with tarantula toxins, the four paddle sequences display distinct toxin binding
      properties, demonstrating that gating-modifier toxins can bind to Cav channels in
      a domain specific fashion. Domain III was the most commonly and strongly
      targeted, and mutagenesis revealed an acidic residue that is important for toxin
      binding. We also measured the lipid partitioning strength of all toxins tested
      and observed a positive correlation with their inhibition of Cav3.1, suggesting a
      key role for membrane partitioning. 

PMID- 27045175
TI  - Cis-trans isomerism in a square-planar platinum(II) complex bearing bulky
      fluorinated phosphane ligands.
AB  - Transition-metal complexes bearing fluorinated phosphane and thiolate ligands has
      been an area of study in recent years and the chemical context of the current
      work is related to the metal-assisted functionalization of fluorinated
      derivatives. The cis and trans isomers of the square-planar complex
      bis[(pentafluorophenyl)diphenylphosphane-kappaP]bis(2,3,5,6
      tetrafluorobenzenethiolato-kappaS)platinum(II), [Pt(C6HF4S)2{P(C6H5)2(C6F5)}2],
      have been crystallized from a single chromatographic fraction and characterized
      by X-ray diffraction analysis. The stabilization of the cis isomer results from
      weak intramolecular pi-stacking interactions and possibly from the formation of a
      C-F...Pt contact, characterized by an F...Pt separation of 2.957 (6) A. The
      natural bond orbital analysis (NBO) for this isomer confirms that the
      corresponding F -> Pt charge transfer accounts for 6.92 kcal mol(-1) in the
      isomer stabilization. Such interactions are not present in the centrosymmetric
      trans isomer. 

PMID- 27045176
TI  - Carboxylate-phenolate tautomerism in 5-[(nitrophenyl)diazenyl]salicylate anions.
AB  - Aryldiazenyl derivatives of salicylic acid and their salts are used as dyes. In
      these structures, the carboxylate groups are engaged in short contacts with the
      cations and in hydrogen bonds with water molecules, if present. If both O atoms
      of the carboxylate group take part in such interactions, the negative charge is
      delocalized over the two atoms. In the absence of hydrogen bonds and contacts
      with cations, the negative charge is localized on one of the O atoms. In the
      crystal structures of tetramethylammonium 2-hydroxy-5-[(E)-(4
      nitrophenyl)diazenyl]benzoate and tetramethylammonium 2-hydroxy-5-[(E)-(2
      nitrophenyl)diazenyl]benzoate, both C4H12N(+).C13H8N3O5(-), all the interactions
      between the cations and anions are weak, and their effect on the geometry of the
      anions is negligible. Under these conditions, the 2-nitro-substituted anion is an
      almost pure phenol-carboxylate tautomer, whereas in the 4-nitro-substituted
      anion, the phenolic H atom is shifted towards the carboxylate group, and thus the
      structure of this anion is intermediate between the phenol-carboxylate and
      phenolate-carboxylic acid tautomeric forms. The probable formation of such an
      intermediate form is supported by quantum chemical calculations. Being the
      characteristic feature of this form, a short distance between the phenolic and
      carboxylate O atoms is observed in the 4-nitro-substituted anion, as well as in
      the structures of some 3,5-dinitrosalicylates reported in the literature. 

PMID- 27045177
TI  - Sulfonate salts of the therapeutic agent dapsone: 4-[(4
      aminophenyl)sulfonyl]anilinium benzenesulfonate monohydrate and 4-[(4
      aminophenyl)sulfonyl]anilinium methanesulfonate monohydrate.
AB  - Dapsone, formerly used to treat leprosy, now has wider therapeutic applications.
      As is the case for many therapeutic agents, low aqueous solubility and high
      toxicity are the main problems associated with its use. Derivatization of its
      amino groups has been widely explored but shows no significant therapeutic
      improvements. Cocrystals have been prepared to understand not only its structural
      properties, but also its solubility and dissolution rate. Few salts of dapsone
      have been described. The title salts, C12H13N2O2S(+).C6H5O3S(-).H2O and
      C12H13N2O2S(+).CH3SO3(-).H2O, crystallize as hydrates and both compounds exhibit
      the same space group (monoclinic, P21/n). The asymmetric unit of each salt
      consists of a 4-[(4-aminophenyl)sulfonyl]anilinium monocation, the corresponding
      sulfonate anion and a water molecule. The cation, anion and water molecule form
      hydrogen-bonded networks through N-H...O=S, N-H...Owater and Owater-H...O=S
      hydrogen bonds. For both salts, the water molecules interact with one sulfonate
      anion and two anilinium cations. The benzenesulfonate salt forms a two
      dimensional network, while the hydrogen bonding within the methanesulfonate salt
      results in a three-dimensional network. 

PMID- 27045178
TI  - Synthesis and characterization of two novel bimetallic macrocyclic complexes
      generated from 1,2,4-triazole-containing semi-rigid ligands and M(NO3)2 units (M
      = Ni and Zn).
AB  - Bimetallic macrocyclic complexes have attracted the attention of chemists and
      various organic ligands have been used as molecular building blocks, but
      supramolecular complexes based on semi-rigid organic ligands containing 1,2,4
      triazole have remained rare until recently. It is easier to obtain novel
      topologies by making use of asymmetric semi-rigid ligands in the self-assembly
      process than by making use of rigid ligands. A new semi-rigid ligand, 3-[(pyridin
      4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine (L), has been
      synthesized and used to generate two novel bimetallic macrocycle complexes,
      namely bis{MU-3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol
      4-amine}bis[(methanol-kappaO)(nitrato-kappa(2)O,O')nickel(II)] dinitrate,
      [Ni2(NO3)2(C17H14N6S)2(CH3OH)2](NO3)2, (I), and bis{MU-3-[(pyridin-4
      ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine}bis[(methanol
      kappaO)(nitrato-kappa(2)O,O')zinc(II)] dinitrate,
      [Zn2(NO3)2(C17H14N6S)2(CH3OH)2](NO3)2, (II), by solution reactions with the
      inorganic salts M(NO3)2 (M = Ni and Zn, respectively) in mixed solvents. In (I),
      two Ni(II) cations with the same coordination environment are linked by L ligands
      through Ni-N bonds to form a bimetallic ring. Compound (I) is extended into a two
      dimensional network in the crystallographic ac plane via N-H...O, O-H...N and O
      H...O hydrogen bonds, and neighbouring two-dimensional planes are parallel and
      form a three-dimensional structure via pi-pi stacking. Compound (II) contains two
      bimetallic rings with the same coordination environment of the Zn(II) cations.
      The Zn(II) cations are bridged by L ligands through Zn-N bonds to form the
      bimetallic rings. One type of bimetallic ring constructs a one-dimensional
      nanotube via O-H...O and N-H...O hydrogen bonds along the crystallographic a
      direction, and the other constructs zero-dimensional molecular cages via O-H...O
      and N-H...O hydrogen bonds. They are interlinked into a two-dimensional network
      in the ac plane through extensive N-H...O hydrogen bonds, and a three-dimensional
      supramolecular architecture is formed via pi-pi interactions between the
      centroids of the benzene rings of the quinoline ring systems. 

PMID- 27045179
TI  - Comparison of the crystal structures of the potent anticancer and anti-angiogenic
      agent regorafenib and its monohydrate.
AB  - Regorafenib {systematic name: 4-[4-({[4-chloro-3
      (trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2
      carboxamide}, C21H15ClF4N4O3, is a potent anticancer and anti-angiogenic agent
      that possesses various activities on the VEGFR, PDGFR, raf and/or flt-3 kinase
      signaling molecules. The compound has been crystallized as polymorphic form I and
      as the monohydrate, C21H15ClF4N4O3.H2O. The regorafenib molecule consists of
      biarylurea and pyridine-2-carboxamide units linked by an ether group. A
      comparison of both forms shows that they differ in the relative orientation of
      the biarylurea and pyridine-2-carboxamide units, due to different rotations
      around the ether group, as measured by the C-O-C bond angles [119.5 (3) degrees 
      in regorafenib and 116.10 (15) degrees  in the monohydrate]. Meanwhile, the
      conformational differences are reflected in different hydrogen-bond networks.
      Polymorphic form I contains two intermolecular N-H...O hydrogen bonds, which link
      the regorafenib molecules into an infinite molecular chain along the b axis. In
      the monohydrate, the presence of the solvent water molecule results in more
      abundant hydrogen bonds. The water molecules act as donors and acceptors, forming
      N-H...O and O-H...O hydrogen-bond interactions. Thus, R4(2)(28) ring motifs are
      formed, which are fused to form continuous spiral ring motifs along the a axis.
      The (trifluoromethyl)phenyl rings protrude on the outside of these motifs and
      interdigitate with those of adjacent ring motifs, thereby forming columns
      populated by halogen atoms. 

PMID- 27045180
TI  - Redetermination of the crystal structure of boron subphthalocyanine chloride (Cl
      BsubPc) enabled by slow train sublimation.
AB  - The crystal structure of boron subphthalocyanine chloride [systematic name:
      chlorido(subphthalocyaninato)boron], C24H12BClN6, a material of widespread
      interest in organic electronic device applications, has been redetermined with a
      higher precision using large single crystals obtained via slow train sublimation.
      Details are given for the construction and operation of the train sublimation
      system, which has been designed to reproducibly yield single crystals suitable
      for diffraction experiments in a manner which approximates the vacuum deposition
      conditions commonly used to fabricate organic electronic devices. Diffraction
      experiments were conducted using two crystal samples and four temperatures (90,
      123, 147 and 295 K), enabling a discussion of changes in the unit cell and
      intermolecular interactions with respect to temperature and in comparison to two
      previously published structures of Cl-BsubPc. The redetermined structure confirms
      the original structure published 41 years ago [Meller & Ossko (1972). Monatsh.
      Chem. 103, 150-155], with significantly improved precision for the geometric
      parameters. Analysis of the crystal structure revealed three intersecting ribbon
      motifs formed through a combination of pi-pi and halogen-pi (specifically B
      Cl...pi) interactions. H atoms were refined independently in order to facilitate
      a thorough discussion of these intermolecular interactions using Hirshfeld
      surface analysis. 

PMID- 27045181
TI  - A two-dimensional zinc(II) coordination polymer based on mixed dimethyl succinate
      and bipyridine ligands: synthesis, structure, thermostability and luminescence
      properties.
AB  - From the viewpoint of crystal engineering, the construction of crystalline
      polymeric materials requires a rational choice of organic bridging ligands for
      the self-assembly process. Multicarboxylate ligands are of particular interest
      due to their strong coordination activity towards metal ions, as well as their
      various coordination modes and versatile conformations. The structural chemistry
      of dicarboxylate-based coordination polymers of transition metals has been
      developed through the grafting of N-containing organic linkers into carboxylate
      bridged transition metal networks. A new luminescent two-dimensional zinc(II)
      coordination polymer containing bridging 2,2-dimethylsuccinate and 4,4'
      bipyridine ligands, namely poly[[aqua(MU2-4,4'-bipyridine-kappa(2)N:N')bis(MU3
      2,2-dimethylbutanedioato)
      kappa(4)O(1),O(1'):O(4):O(4');kappa(5)O(1):O(1),O(4):O(4),O(4')-dizinc(II)]
      dihydrate], {[Zn2(C6H8O4)2(C10H8N2)(H2O)].2H2O}n, has been synthesized under
      hydrothermal conditions and characterized by single-crystal X-ray diffraction and
      elemental, IR and thermogravimetric analyses. In the structure, the 2,2
      dimethylsuccinate ligands link linear tetranuclear Zn(II) subunits into one
      dimensional chains along the c axis. 4,4'-Bipyridine acts as a tethering ligand
      expanding these one-dimensional chains into a two-dimensional layered structure.
      Hydrogen-bonding interactions between the water molecules (both coordinated and
      free) and carboxylate O atoms strengthen the packing of the layers. Furthermore,
      the luminescence properties of the complex were investigated. The compound
      exhibits a blue photoluminescence in the solid state at room temperature and may
      be a good candidate for potential hybrid inorganic-organic photoactive materials.

PMID- 27045182
TI  - pi-pi stacking motifs in dialkylbis{5-[(E)-2-aryldiazen-1-yl]-2
      hydroxybenzoato}tin(IV) complexes.
AB  - The diorganotin(IV) complexes of 5-[(E)-2-aryldiazen-1-yl]-2-hydroxybenzoic acid
      are of interest because of their structural diversity in the crystalline state
      and their interesting biological activity. The structures of dimethylbis{2
      hydroxy-5-[(E)-2-(4-methylphenyl)diazen-1-yl]benzoato}tin(IV),
      [Sn(CH3)2(C14H11N2O3)2], and di-n-butylbis{2-hydroxy-5-[(E)-2-(4
      methylphenyl)diazen-1-yl]benzoato}tin(IV) benzene hemisolvate,
      [Sn(C4H9)2(C14H11N2O3)2].0.5C6H6, exhibit the usual skew-trapezoidal bipyramidal
      coordination geometry observed for related complexes of this class. Each
      structure has two independent molecules of the Sn(IV) complex in the asymmetric
      unit. In the dimethyltin structure, intermolecular O-H...O hydrogen bonds and a
      very weak Sn...O interaction link the independent molecules into dimers. The
      planar carboxylate ligands lend themselves to pi-pi stacking interactions and the
      diversity of supramolecular structural motifs formed by these interactions has
      been examined in detail for these two structures and four closely related
      analogues. While there are some recurring basic motifs amongst the observed
      stacking arrangements, such as dimers and step-like chains, variations through
      longitudinal slipping and inversion of the direction of the overlay add
      complexity. The pi-pi stacking motifs in the two title complexes are combinations
      of some of those observed in the other structures and are the most complex of the
      structures examined. 

PMID- 27045183
TI  - Crystal structure and bonding analysis of the first dinuclear calcium(II)-proton
      pump inhibitor (PPI) 'butterfly molecule': a combined microcrystal synchrotron
      and DFT study.
AB  - Proton-pump inhibitors (PPI) are prodrugs used widely to treat acid-related
      diseases since the late 1980s. After an extensive research effort it has become
      clear that the fundamental interactions between metal atoms and PPIs are of
      paramount importance for both drug release and long-term therapeutic safety.
      Unfortunately, until now, very little information has been available on this
      topic. In this paper, we report the crystal structure analysis of a novel calcium
      PPI compound incorporating bridging and terminal deprotonated (R)-rabeprazole
      tricyclic ligands (L), namely bis[MU-(R)-2-({[4-(3-methoxypropoxy)-3
      methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1
      ido]bis{dimethanol[(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2
      yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]calcium(II)}
      methanol hexasolvate, [Ca2(C20H22N3O4S)4(CH3OH)4].6CH3OH or
      [Ca2(L)4(CH3OH)4].6CH3OH, which crystallizes from methanol in the polar C2 space
      group. Using low-temperature microcrystal synchrotron radiation, we demonstrate
      that this compound is in the form of a beautiful 'butterfly molecule', consisting
      of a C2-symmetric dinuclear (CH3OH)2LCa(II)(MU2-L)2Ca(II)L(HOCH3)2 framework. A
      large amount of disorder is found within the bridging L ligand and the
      conformation of the fused tetrahydrofuran ring exhibits great variety. All the
      sulfinyl groups remain intact and the nonbonded Ca...Ca distance is significantly
      longer than in other calcium dimers, indicating steric hindrance in the bridging
      ligands. Considerable hydrogen bonding and aromatic C-H...pi interactions co
      operate to stabilize the whole complex, as well as to facilitate supramolecular
      assembly. Additional investigations into the bond nature were made using density
      functional theory (DFT) methods at the B3LYP/6-31G(d) level; geometry
      optimization, Mulliken atomic charges, MEP (molecular electrostatic potential),
      HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular
      orbital), TDOS (total density of states), PDOS (partial density of states), COOP
      (crystal orbital overlap population) and vibrational spectra were
      calculated/recorded and assessed carefully. 

PMID- 27045184
TI  - Supramolecular hydrogen-bonding patterns in the organic-inorganic hybrid compound
      bis(4-amino-5-chloro-2,6-dimethylpyrimidinium) tetrathiocyanatozinc(II)-4-amino-5
      chloro-2,6-dimethylpyrimidine-water (1/2/2).
AB  - Zinc thiocyanate complexes have been found to be biologically active compounds.
      Zinc is also an essential element for the normal function of most organisms and
      is the main constituent in a number of metalloenzyme proteins. Pyrimidine and
      aminopyrimidine derivatives are biologically very important as they are
      components of nucleic acids. Thiocyanate ions can bridge metal ions by employing
      both their N and S atoms for coordination. They can play an important role in
      assembling different coordination structures and yield an interesting variety of
      one-, two- and three-dimensional polymeric metal-thiocyanate supramolecular
      frameworks. The structure of a new zinc thiocyanate-aminopyrimidine organic
      inorganic compound, (C6H9ClN3)2[Zn(NCS)4].2C6H8ClN3.2H2O, is reported. The
      asymmetric unit consist of half a tetrathiocyanatozinc(II) dianion, an
      uncoordinated 4-amino-5-chloro-2,6-dimethylpyrimidinium cation, a 4-amino-5
      chloro-2,6-dimethylpyrimidine molecule and a water molecule. The Zn(II) atom
      adopts a distorted tetrahedral coordination geometry and is coordinated by four N
      atoms from the thiocyanate anions. The Zn(II) atom is located on a special
      position (twofold axis of symmetry). The pyrimidinium cation and the pyrimidine
      molecule are not coordinated to the Zn(II) atom, but are hydrogen bonded to the
      uncoordinated water molecules and the metal-coordinated thiocyanate ligands. The
      pyrimidine molecules and pyrimidinium cations also form base-pair-like structures
      with an R2(2)(8) ring motif via N-H...N hydrogen bonds. The crystal structure is
      further stabilized by intermolecular N-H...O, O-H...S, N-H...S and O-H...N
      hydrogen bonds, by intramolecular N-H...Cl and C-H...Cl hydrogen bonds, and also
      by pi-pi stacking interactions. 

PMID- 27045185
TI  - Nontypical iodine-halogen bonds in the crystal structure of (3E)-8-chloro-3
      iodomethylidene-2,3-dihydro-1,4-oxazino[2,3,4-ij]quinolin-4-ium triiodide.
AB  - Two kinds of iodine-iodine halogen bonds are the focus of our attention in the
      crystal structure of the title salt, C12H8ClINO(+).I3(-), described by X-ray
      diffraction. The first kind is a halogen bond, reinforced by charges, between the
      I atom of the heterocyclic cation and the triiodide anion. The second kind is the
      rare case of a halogen bond between the terminal atoms of neighbouring triiodide
      anions. The influence of relatively weakly bound iodine inside an asymmetric
      triiodide anion on the thermal and Raman spectroscopic properties has been
      demonstrated. 

PMID- 27045186
TI  - Six polycyclic pyrimidoazepine derivatives: syntheses, molecular structures and
      supramolecular assembly.
AB  - A versatile synthetic method has been developed for the formation of variously
      substituted polycyclic pyrimidoazepine derivatives, formed by nucleophilic
      substitution reactions on the corresponding chloro-substituted compounds; the
      reactions can be promoted either by conventional heating in basic solutions or by
      microwave heating in solvent-free systems. Thus, (6RS)-6,11-dimethyl-3,5,6,11
      tetrahydro-4H-benzo[b]pyrimido[5,4-f]azepin-4-one, C14H15N3O, (I), was isolated
      from a solution containing (6RS)-4-chloro-8-hydroxy-6,11-dimethyl-6,11-dihydro-5H
      benzo[b]pyrimido[5,4-f]azepine and benzene-1,2-diamine; (6RS)-4-butoxy-6,11
      dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepin-8-ol, C18H23N3O2, (II),
      was formed by reaction of the corresponding 6-chloro compound with butanol, and
      (RS)-4-dimethylamino-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepin
      8-ol, C16H20N4O, (III), was formed by reaction of the chloro analogue with
      alkaline dimethylformamide. (6RS)-N-Benzyl-8-methoxy-6,11-dimethyl-6,11-dihydro
      5H-benzo[b]pyrimido[5,4-f]azepin-4-amine, C22H24N4O, (IV), (6RS)-N-benzyl-6
      methyl-1,2,6,7-tetrahydropyrimido[5',4':6,7]azepino[3,2,1-hi]indol-8-amine,
      C22H22N4, (V), and (7RS)-N-benzyl-7-methyl-2,3,7,8-tetrahydro-1H
      pyrimido[5',4':6,7]azepino[3,2,1-ij]quinolin-9-amine, C23H24N4, (VI), were all
      formed by reaction of the corresponding chloro compounds with benzylamine under
      microwave irradiation. In each of compounds (I)-(IV) and (VI), the azepine ring
      adopts a conformation close to the boat form, with the C-methyl group in a quasi
      equatorial site, whereas the corresponding ring in (V) adopts a conformation
      intermediate between the twist-boat and twist-chair forms, with the C-methyl
      group in a quasi-axial site. No two of the structures of (I)-(VI) exhibit the
      same range of intermolecular hydrogen bonds: different types of sheet are formed
      in each of (I), (II), (V) and (VI), and different types of chain in each of (III)
      and (IV). 

PMID- 27045187
TI  - A three-dimensional mixed-valence Cu(II)/Cu(I) coordination polymer constructed
      from biphenyl-3,4',5-tricarboxylate and 1,4-bis(1H-imidazol-1-yl)benzene ligands.
AB  - Coordination polymers (CPs) built by coordination bonds between metal
      ions/clusters and multidentate organic ligands exhibit fascinating structural
      topologies and potential applications as functional solid materials. The title
      coordination polymer, poly[diaquabis(MU4-biphenyl-3,4',5-tricarboxylato
      kappa(4)O(3):O(3'):O(4'):O(5))tris[MU2-1,4-bis(1H-imidazol-1-yl)benzene
      kappa(2)N(3):N(3')]dicopper(II)dicopper(I)],
      [Cu(II)2Cu(I)2(C15H7O6)2(C12H10N4)3(H2O)2]n, was crystallized from a mixture of
      biphenyl-3,4',5-tricarboxylic acid (H3bpt), 1,4-bis(1H-imidazol-1-yl)benzene (1,4
      bib) and copper(II) chloride in a water-CH3CN mixture under solvothermal reaction
      conditions. The asymmetric unit consists of two crystallographically independent
      Cu atoms, one of which is Cu(II), while the other has been reduced to the Cu(I)
      ion. The Cu(II) centre is pentacoordinated by three O atoms from three bpt(3-)
      ligands, one N atom from a 1,4-bib ligand and one O atom from a coordinated water
      molecule, and the coordination geometry can be described as distorted trigonal
      bipyramidal. The Cu(I) atom exhibits a T-shaped geometry (CuN2O) coordinated by
      one O atom from a bpt(3-) ligand and two N atoms from two 1,4-bib ligands. The
      Cu(II) atoms are extended by bpt(3-) and 1,4-bib linkers to generate a two
      dimensional network, while the Cu(I) atoms are linked by 1,4-bib ligands, forming
      one-dimensional chains along the [20-1] direction. In addition, the completely
      deprotonated MU4-eta(1):eta(1):eta(1):eta(1) bpt(3-) ligands bridge one Cu(I) and
      three Cu(II) cations along the a (or [100]) direction to form a three-dimensional
      framework with a (10(3))2(10)2(4(2).6.10(2).12)2(4(2).6.8(2).10)2(8) topology via
      a 2,2,3,4,4-connected net. An investigation of the magnetic properties indicated
      a very weak ferromagnetic behaviour. 

PMID- 27045188
TI  - Reclassification of Enterobacter oryziphilus and Enterobacter oryzendophyticus as
      Kosakonia oryziphila comb. nov. and Kosakonia oryzendophytica comb. nov.
AB  - The taxonomic positions of Enterobacter oryziphilus and Enterobacter
      oryzendophyticus were re-examined on the basis of concatenated partial rpoB,
      atpD, gyrB and infB gene sequence analysis. The reconstructed phylogenetic tree
      based upon concatenated partial rpoB, atpD, gyrB and infB gene sequences clearly
      showed that E. oryziphilus and E. oryzendophyticus and all defined species of the
      genus Kosakonia form a clade separate from other genera of the family
      Enterobacteriaceae, and, therefore, these species of the genus Enterobacter
      should be transferred to the genus Kosakonia. E. oryziphilus and E.
      oryzendophyticus are reclassified as K. oryziphila comb. nov. (type strain
      REICA_142T=LMG 26429T=NCCB 100393T) and K. oryzendophytica comb. nov. (type
      strain REICA_082T=LMG 26432T=NCCB 100390T), respectively. 

PMID- 27045189
TI  - Explicit inclusion of treatment in prognostic modeling was recommended in
      observational and randomized settings.
AB  - OBJECTIVES: To compare different methods to handle treatment when developing a
      prognostic model that aims to produce accurate probabilities of the outcome of
      individuals if left untreated. STUDY DESIGN AND SETTING: Simulations were
      performed based on two normally distributed predictors, a binary outcome, and a
      binary treatment, mimicking a randomized trial or an observational study.
      Comparison was made between simply ignoring treatment (SIT), restricting the
      analytical data set to untreated individuals (AUT), inverse probability weighting
      (IPW), and explicit modeling of treatment (MT). Methods were compared in terms of
      predictive performance of the model and the proportion of incorrect treatment
      decisions. RESULTS: Omitting a genuine predictor of the outcome from the
      prognostic model decreased model performance, in both an observational study and
      a randomized trial. In randomized trials, the proportion of incorrect treatment
      decisions was smaller when applying AUT or MT, compared to SIT and IPW. In
      observational studies, MT was superior to all other methods regarding the
      proportion of incorrect treatment decisions. CONCLUSION: If a prognostic model
      aims to produce correct probabilities of the outcome in the absence of treatment,
      ignoring treatments that affect that outcome can lead to suboptimal model
      performance and incorrect treatment decisions. Explicitly, modeling treatment is
      recommended.

PMID- 27045190
TI  - Which is the best treatment for prosthetic joint infections due to
      Propionibacterium acnes: need for further biofilm in vitro and experimental
      foreign-body in vivo studies?

PMID- 27045191
TI  - Reasons People Surrender Unowned and Owned Cats to Australian Animal Shelters and
      Barriers to Assuming Ownership of Unowned Cats.
AB  - Most cats surrendered to nonhuman animal shelters are identified as unowned, and
      the surrender reason for these cats is usually simply recorded as "stray." A
      cross-sectional study was conducted with people surrendering cats to 4 Australian
      animal shelters. Surrenderers of unowned cats commonly gave surrender reasons
      relating to concern for the cat and his/her welfare. Seventeen percent of
      noncaregivers had considered adopting the cat. Barriers to assuming ownership
      most commonly related to responsible ownership concerns. Unwanted kittens
      commonly contributed to the decision to surrender for both caregivers and
      noncaregivers. Nonowners gave more surrender reasons than owners, although many
      owners also gave multiple surrender reasons. These findings highlight the
      multifactorial nature of the decision-making process leading to surrender and
      demonstrate that recording only one reason for surrender does not capture the
      complexity of the surrender decision. Collecting information about multiple
      reasons for surrender, particularly reasons for surrender of unowned cats and
      barriers to assuming ownership, could help to develop strategies to reduce the
      number of cats surrendered. 

PMID- 27045192
TI  - Editorial: Working towards an understanding of bone disease in HIV.

PMID- 27045194
TI  - Cell separation: Potentials and pitfalls.
AB  - Cell separation techniques play an indispensable part in numerous basic
      biological studies and even clinical settings. Although various cell isolation
      methods with diverse applications have been devised so far, not all of them have
      been able to gain widespread popularity among researchers and clinicians. There
      is not a single method known to be advantageous over all cell isolation
      techniques, and in fact, it is the researcher's aim in performing a study that
      determines the most suitable method. A perfect method for one study might not be
      necessarily a proper choice for another and likewise, expensive and complex
      isolation methods might not always be the best choices. There are several
      criteria such as cell purity, viability, activation status, and frequency that
      need to be given serious thought before selecting an isolation technique.
      Moreover, time and cost are two of the key elements that should be taken into
      consideration before implementing a project. Hence, here we provide a succinct
      description of six more popular cell separation methods with respect to their
      principles, advantages, and disadvantages as well as their most common
      applications. We further provide several key features of each technique so that
      it helps the researchers to take the first step toward opting for the best method
      that fits well into their projects.

PMID- 27045195
TI  - Women's Experiences and Preferences for Service Delivery of Non-Invasive Prenatal
      Testing for Aneuploidy in a Public Health Setting: A Mixed Methods Study.
AB  - Non-invasive prenatal testing (NIPT) for aneuploidy is currently only available
      in the UK through the private sector outside of the research arena. As part of an
      implementation study in the UK National Health Service we conducted a mixed
      methods study to assess women's experience of being offered NIPT using validated
      measures of decisional conflict, decisional regret and anxiety. Clinical service
      preferences were also explored. Women with a Down syndrome screening risk >1:1000
      were invited to take part in the study and offered NIPT, NIPT and invasive
      testing (for women with a risk above 1:150) or no further testing. A cross
      sectional survey and semi-structured interviews were conducted at two time
      points; at the time of testing and one month following receipt of results (or
      equivalent for NIPT decliners). In total, 845 questionnaires and 81 interviews
      were analysed. The main motivation to accept NIPT was for reassurance (30.8%).
      Decisional conflict occurred in a minimal number of cases (3.8%), however, none
      of the participants experienced decisional regret. Around a third (29.9%) of
      women had elevated anxiety at the time of testing, including intermediate risk
      women who traditionally would not be offered further testing (54.4% high risk;
      20.1% medium risk), a finding supported through the qualitative interviews where
      prolonged or additional anxiety was found to occur in some medium risk cases.
      Women were overwhelmingly positive about the opportunity to have a test that was
      procedurally safe, accurate, reduced the need for invasive testing and identified
      cases of Down syndrome that might otherwise have been missed. Reassurance was
      identified as the main motivator for accepting NIPT, particularly amongst medium
      risk women, with high risk women inclined to accept NIPT to inform decisions
      around invasive testing. The current turnaround time for test result was
      identified as a key limitation. All the women interviewed thought NIPT should be
      adopted as part of NHS clinical practice, with the majority favouring NIPT
      offered as a first-line test. Our study highlights the potential that NIPT has to
      positively impact women's experience of prenatal testing for aneuploidy. 

PMID- 27045196
TI  - Optogenetically inspired deep brain stimulation: linking basic with clinical
      research.
AB  - In the last decade, optogenetics has revolutionised the neurosciences. The
      technique, which allows for cell-type specific excitation and inhibition of
      neurons in the brain of freely moving rodents, has been used to tighten the links
      of causality between neural activity and behaviour. Optogenetics is also enabling
      an unprecedented characterisation of circuits and their dysfunction in a number
      of brain diseases, above all those conditions that are not caused by
      neurodegeneration. Notable progress has been made in addiction, depression and
      obsessive-compulsive disorders, as well as other anxiety disorders. By extension,
      the technique has also been used to propose blueprints for innovative rational
      treatment of these diseases. The goal is to design manipulations that disrupt
      pathological circuit function or restore normal activity. This can be achieved by
      targeting specific projections in order to apply specific stimulation protocols
      validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a
      number of cases, specific forms of pathological synaptic plasticity have been
      implicated. For example, addictive drugs via strong increase of dopamine trigger
      a myriad of alterations of glutamate and gamma-aminobutyric acid transmission,
      also called drug-evoked synaptic plasticity. This opens the way to the design of
      optogenetic reversal protocols, which might restore normal transmission with the
      hope to abolish the pathological behaviour. Several proof of principle studies
      for this approach have recently been published. However, for many reasons,
      optogenetics will not be translatable to human applications in the near future.
      Here, we argue that an intermediate step is novel deep brain stimulation (DBS)
      protocols that emulate successful optogenetic approaches in animal models. We
      provide a roadmap for a translational path to rational, optogenetically inspired
      DBS protocols to refine existing approaches and expand to novel indications.

PMID- 27045197
TI  - Garlic attenuates histological and histochemical alterations in livers of
      Schistosoma mansoni infected mice.
AB  - Interest in screening for new anti-schistosomal agents is growing because of
      increased concerns about resistance to and safety of praziquantel. We
      investigated the anti-schistosomal action of prophylactic and therapeutic doses
      of garlic on the histological and histochemical alterations caused by Schistosoma
      mansoni infection. Livers of infected mice were characterized by granulomas,
      periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration
      and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant
      depletion of carbohydrates and increased lipid vacuoles also were observed. All
      garlic regimens caused suppression of granuloma formation and amelioration of
      histological and histochemical changes; the continuous treatment protocol
      produced the best results. Garlic appears to be a safe and economical anti
      schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis. 

PMID- 27045198
TI  - The effects of sulforaphane on canine osteosarcoma proliferation and invasion.
AB  - Recent evidence in in vitro and in vivo models suggests that sulforaphane (SFN),
      found in raw cruciferous vegetables, may have utility in chemoprevention, as an
      antineoplastic agent and as a free radical scavenger. The effects of SFN alone or
      with doxorubicin on cell viability were examined, as well as cell cycle kinetics,
      invasion capabilities and apoptosis in three canine osteosarcoma cell line (D17,
      OS 2.4 and HMPOS). Results showed that SFN could not induce cell death at
      potentially physiological concentrations (<50 MUM), but significantly diminished
      cell invasion and downregulation of focal adhesion kinase (FAK) signaling. Modest
      cell cycle changes were observed in each cell line. When doxorubicin was used in
      conjunction with SFN, there was a protective effect to doxorubicin-induced
      cytotoxicity in D17 and OS 2.4 cells. Further studies examining SFN as a
      supplement are warranted, particularly in light of pro-proliferative and
      cytoprotective properties in canine osteosarcoma.

PMID- 27045199
TI  - Are hysterectomies necessary? Racial-ethnic differences in women's attitudes.
AB  - There is a dearth of comparative information about how women from diverse social
      locations think about, talk about, and experience the various types of
      reproductive aging. In this article I analyze racial-ethnic differences in
      attitudes toward surgically induced menopause (hysterectomy) utilizing data from
      an interview study of 130 menopausal women. African American women in this study
      were more suspect of doctors' initial offers of hysterectomies than European
      American women, with the former group of interviewees still fearing a legacy of
      racial-ethnic discrimination within medical institutions. Only after seeking a
      second opinion or finding a trustworthy doctor did African American women feel
      comfortable accepting a hysterectomy. European American interviewees were not as
      wary as their African American counterparts and sometimes reported wishing for a
      hysterectomy. I argue that attitudes toward hysterectomy must be contextualized
      within women's experiences of racial-ethnic oppression and privilege to be fully
      understood. 

PMID- 27045200
TI  - 2-Deoxy-d-glucose is a potent inhibitor of biofilm growth in Escherichia coli.
AB  - Escherichia coli strain 15 (ATCC 9723), which forms robust biofilms, was grown
      under optimal biofilm conditions in NaCl-free Luria-Bertani broth (LB*) or in LB*
      supplemented with one of the non-metabolizable analogues 2-deoxy-d-glucose (2DG),
      methyl alpha-d-mannopyranoside (alphaMM), or methyl alpha-d-glucopyranoside
      (alphaMG). Biofilm growth was inhibited by mannose analogue 2DG even at very low
      concentration in unbuffered medium, and the maximal inhibition was enhanced in
      the presence of either 100 mM KPO4 or 100 mM MOPS, pH 7.5; in buffered medium,
      concentrations of 0.02 % (1.2 mM) or more inhibited growth nearly completely. In
      contrast, mannose analogue alphaMM, which should not be able to enter the cells
      but has been reported to inhibit biofilm growth by binding to FimH, did not
      exhibit strong inhibition even at concentrations up to 1.8 % (108 mM). The
      glucose analogue alphaMG inhibited biofilm growth, but much less strongly than
      did 2DG. None of the analogues inhibited planktonic growth or caused a change in
      pH of the unbuffered medium. Similar inhibitory effects of the analogues were
      observed in minimal medium. The effects were not strain-specific, as 2DG and
      alphaMG also inhibited the weak biofilm growth of E. coli K12.

PMID- 27045202
TI  - A novel approach for precisely controlled multiple cell patterning in
      microfluidic chips by inkjet printing and the detection of drug metabolism and
      diffusion.
AB  - In this work we report the use of inkjet printing as a precise and convenient
      means for microscale cell patterning in microfluidic chips followed by cell co
      culture, stimulation and analysis. A self-made inkjet printing device was
      manufactured with adjustable parameters, which was capable of multiple cell
      printing within biocompatible materials. Sodium alginate was used as a printing
      matrix for cell encapsulation, and precisely distributed cell arrays on glass
      slides were obtained by accurate software controlled printing. By covering a PDMS
      layer with the corresponding microchannels onto the cell array substrate and
      subsequently injecting an ion cross-linking reagent, the cells containing
      alginate arrays gelated immediately and were immobilized on the bottom of the
      microchip, which could be utilized for cell culture and analysis. HepG2 cells and
      U251 cells were successfully co-patterned in the microchip and used for drug
      metabolism and diffusion experiment to imitate the in vivo situation, as a means
      to ascertain the capability of the system for precise microscale cell patterning
      in a microchip. The prodrug tegafur was metabolized by HepG2 cells into the
      active anticancer compound 5-fluorouracil and this produced an adverse gradient
      effect on U251 cells according to the distance from the HepG2 cells. The
      developed approach presented a feasible way to integrate inkjet cell printing and
      microfluidic chips for the first time, which is proved to be capable of spatially
      controlled printing of multiple kinds of cells into a microchip for cell culture,
      stimulation and analysis, which could be applied to tissue engineering, drug
      testing and related areas. We envision that the approach will help significantly
      increase the cell patterning efficacy in microfluidic chips as well as reduce the
      extent of laborious experimental work.

PMID- 27045203
TI  - MP2 Study of Physisorption of Molecular Hydrogen onto Defective Nanotubes:
      Cooperative Effect in Stone-Wales Defects.
AB  - We use large-scale MP2 calculations to investigate the physisorption of molecular
      hydrogen on (9,0) defective carbon nanotubes (CNTs) of C72H18. These large
      (supra)molecular systems are typically studied using conventional DFT methods,
      which do not describe well the van der Waals interactions responsible for this
      process. Here we use CCSD(T)-calibrated MP2 calculations to estimate binding
      energies by considering four defective structures (hydrogenated divacancy,
      octagon-pentagon, and two Stone-Wales defects). The largest physisorption
      energies for the nondefective CNT are for configurations in which H2 points
      toward the center of one ring. The computed interaction energies for defect-free
      CNT are in the range 5.7 to 5.9 kJ/mol, in good agreement with the experimental
      value of 5.98 kJ/mol. The defects introduced in the (9,0)-CNT increase the
      surface area of the nanotube, such that the largest surface in found in the 55-77
      Stone-Wales defective CNT that furthermore is the most aromatic. Only that defect
      enlarges the physisorption binding energy, which can become >25% larger.
      Moreover, a cooperative effect in the adsorption of H2 not appearing in the
      regular structure is found. 

PMID- 27045201
TI  - Perioperative circulating tumor cell detection: Current perspectives.
AB  - Primary cancer resections and in selected cases surgical metastasectomies
      significantly improve survival, however many patients develop recurrences.
      Circulating tumor cells (CTCs) function as an independent marker that could be
      used in the prognostication of different cancers. Sampling of blood and bone
      marrow compartments during cancer resections is a unique opportunity to increase
      individual tumor cell capture efficiency. This review will address the diagnostic
      and therapeutic potentials of perioperative tumor isolation and highlight the
      focus of future studies on characterization of single disseminated cancer cells
      to identify targets for molecular therapy and immune escape mechanisms.

PMID- 27045204
TI  - Impact of oral probiotics on neurodevelopmental outcomes in preterm infants.
AB  - OBJECTIVE: The aim of the study was to evaluate the neurodevelopment outcomes of
      very low birth weight (VLBW) preterm infants supplemented with oral probiotics
      for the prevention of necrotizing enterocolitis (NEC). METHODS: A prospective
      follow-up study was performed in a cohort of VLBW preterm infants enrolled in a
      single center randomized controlled clinical trial to evaluate the efficacy of
      oral probiotics for the prevention of NEC. Cognitive and neuromotor developments
      were assessed by using the Bayley scales of infant development II. Sensory and
      neurological performance was evaluated by standard techniques. The primary
      outcome was neurodevelopmental impairment at 18-24 months' corrected age.
      RESULTS: A total of 400 infants completed the trial protocol. Of the 370 infants
      eligible for follow-up, 249 infants (124 in the probiotics group and 125 in the
      control group) were evaluated. There was no significant difference in any of the
      neurodevelopmental and sensory outcomes between the two groups. CONCLUSION: Oral
      probiotic given to VLBW infants to reduce the incidense and severity of NEC
      started with the first feed did not affect neuromotor, neurosensory and cognitive
      outcomes at 18-24 months' corrected age.

PMID- 27045205
TI  - Asymmetry During Maximal Sprint Performance in 11- to 16-Year-Old Boys.
AB  - PURPOSE: The aim of this study was to examine the influence of age and maturation
      upon magnitude of asymmetry in the force, stiffness and the spatiotemporal
      determinants of maximal sprint speed in a large cohort of boys. METHODS: 344 boys
      between the ages of 11 and 16 years completed an anthropometric assessment and a
      35 m sprint test, during which sprint performance was recorded via a ground-level
      optical measurement system. Maximal sprint velocity, as well as asymmetry in
      spatiotemporal variables, modeled force and stiffness data were established for
      each participant. For analysis, participants were grouped into chronological age,
      maturation and percentile groups. RESULTS: The range of mean asymmetry across age
      groups and variables was 2.3-12.6%. The magnitude of asymmetry in all the sprint
      variables was not significantly different across age and maturation groups (p >
      .05), except relative leg stiffness (p < .05). No strong relationships between
      asymmetry in sprint variables and maximal sprint velocity were evident (rs <
      .39). CONCLUSION: These results provide a novel benchmark for the expected
      magnitude of asymmetry in a large cohort of uninjured boys during maximal sprint
      performance. Asymmetry in sprint performance is largely unaffected by age or
      maturation and no strong relationships exist between the magnitude of asymmetry
      and maximal sprint velocity.

PMID- 27045206
TI  - A Biofunctional Molecular Beacon for Detecting Single Base Mutations in Cancer
      Cells.
AB  - The development of a convenient and sensitive biosensing system to detect
      specific DNA sequences is an important issue in the field of genetic disease
      therapy. As a classic DNA detection technique, molecular beacon (MB) is often
      used in the biosensing system. However, it has intrinsic drawbacks, including
      high assay cost, complicated chemical modification, and operational complexity.
      In this study, we developed a simple and cost-effective label-free
      multifunctional MB (LMMB) by integrating elements of polymerization primer,
      template, target recognition, and G-quadruplex into one entity to detect target
      DNA. The core technique was accomplished by introducing a G-hairpin that features
      fragments of both G-quadruplex and target DNA recognition in the G-hairpin stem.
      Hybridization between LMMB and target DNA triggered conformational change between
      the G-hairpin and the common C-hairpin, resulting in significant SYBR-green
      signal amplification. The hybridization continues to the isothermal circular
      strand-displacement polymerization and accumulation of the double-stranded
      fragments, causing the uninterrupted extension of the LMMB without a need of
      chemical modification and other assistant DNA sequences. The novel and
      programmable LMMB could detect target DNA with sensitivity at 250 pmol/l with a
      linear range from 2 to 100 nmol/l and the relative standard deviation of 7.98%.
      The LMMB could sense a single base mutation from the normal DNA, and polymerase
      chain reaction (PCR) amplicons of the mutant-type cell line from the wild-type
      one. The total time required for preparation and assaying was only 25 minutes.
      Apparently, the LMMB shows great potential for detecting DNA and its mutations in
      biosamples, and therefore it opens up a new prospect for genetic disease therapy.

PMID- 27045207
TI  - A Novel p19 Fusion Protein as a Delivery Agent for Short-interfering RNAs.
AB  - RNA interference (RNAi) is the biological mechanism that allows targeted gene
      knockdown through the addition of exogenous short-interfering RNAs (siRNAs) to
      cells and organisms. RNAi has revolutionized cell biology and holds enormous
      potential for human therapy. One of the major challenges facing RNAi as a therapy
      is achieving efficient and nontoxic delivery of siRNAs into the cell cytoplasm,
      since their highly anionic character precludes their passage across the cell
      membrane unaided. Herein, we report a novel fusion protein between the
      tombusviral p19 protein, which binds siRNAs with picomolar affinity, and the
      "TAT" peptide (RKKRRQRRRR), which is derived from the transactivator of
      transcription (TAT) protein of the human immunodeficiency virus and acts as a
      cell-penetrating peptide. We demonstrate that this fusion protein, 2x-p19-TAT,
      delivers siRNAs into the cytoplasm of human hepatoma cells where they elicit
      potent and sustained gene knockdown activity without toxic effects. 

PMID- 27045208
TI  - The Gene Targeting Approach of Small Fragment Homologous Replacement (SFHR)
      Alters the Expression Patterns of DNA Repair and Cell Cycle Control Genes.
AB  - Cellular responses and molecular mechanisms activated by exogenous DNA that
      invades cells are only partially understood. This limits the practical use of
      gene targeting strategies. Small fragment homologous replacement (SFHR) uses a
      small exogenous wild-type DNA fragment to restore the endogenous wild-type
      sequence; unfortunately, this mechanism has a low frequency of correction. In
      this study, we used a mouse embryonic fibroblast cell line with a stably
      integrated mutated gene for enhanced green fluorescence protein. The restoration
      of a wild-type sequence can be detected by flow cytometry analysis. We
      quantitatively analyzed the expression of 84 DNA repair genes and 84 cell cycle
      control genes. Peculiar temporal gene expression patterns were observed for both
      pathways. Different DNA repair pathways, not only homologous recombination, as
      well as the three main cell cycle checkpoints appeared to mediate the cellular
      response. Eighteen genes were selected as highly significant target/effectors of
      SFHR. We identified a wide interconnection between SFHR, DNA repair, and cell
      cycle control. Our results increase the knowledge of the molecular mechanisms
      involved in cell invasion by exogenous DNA and SFHR. Specific molecular targets
      of both the cell cycle and DNA repair machineries were selected for manipulation
      to enhance the practical application of SFHR. 

PMID- 27045209
TI  - Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in
      Recessive Dystrophic Epidermolysis Bullosa Keratinocytes.
AB  - Clonal gene therapy protocols based on the precise manipulation of epidermal stem
      cells require highly efficient gene-editing molecular tools. We have combined
      adeno-associated virus (AAV)-mediated delivery of donor template DNA with
      transcription activator-like nucleases (TALE) expressed by adenoviral vectors to
      address the correction of the c.6527insC mutation in the COL7A1 gene, causing
      recessive dystrophic epidermolysis bullosa in a high percentage of Spanish
      patients. After transduction with these viral vectors, high frequencies of
      homology-directed repair were found in clones of keratinocytes derived from a
      recessive dystrophic epidermolysis bullosa (RDEB) patient homozygous for the
      c.6527insC mutation. Gene-edited clones recovered the expression of the COL7A1
      transcript and collagen VII protein at physiological levels. In addition,
      treatment of patient keratinocytes with TALE nucleases in the absence of a donor
      template DNA resulted in nonhomologous end joining (NHEJ)-mediated indel
      generation in the vicinity of the c.6527insC mutation site in a large proportion
      of keratinocyte clones. A subset of these indels restored the reading frame of
      COL7A1 and resulted in abundant, supraphysiological expression levels of mutant
      or truncated collagen VII protein. Keratinocyte clones corrected both by homology
      directed repair (HDR) or NHEJ were used to regenerate skin displaying collagen
      VII in the dermo-epidermal junction. 

PMID- 27045210
TI  - Hyperuricemia is associated with the increase of insulin release in non-obese
      subjects with normal glucose tolerance.
AB  - AIM: To determine whether hyperuricemia is associated with the early phase and
      late phase of insulin release in apparently healthy non-obese subjects with
      normal glucose tolerance. MATERIALS AND METHODS: A population-based cross
      sectional study was performed. Apparently healthy individuals aged 20 to 65 years
      were eligible to participate. Smoking, alcohol intake >=30 g per day, obesity,
      glomerulopathies, hepatic disease, malignancy, cardiovascular disease, and
      medical treatment in the last 3 months, were exclusion criteria. Hyperuricemia
      was defined by fasting uric acid levels >=6 mg/dL and >=7 mg/dL for women and
      men, respectively. Insulin release was evaluated by estimating the early and late
      phases of insulin release. The association between hyperuricemia (independent
      variables) and insulin release (dependent variables) was estimated using multiple
      linear regression analysis. RESULTS: A total of 123 subjects, without significant
      differences in age (32.4 +/- 12.8 and 34.7 +/- 9.9 y), body mass index (25.3 +/-
      3.7 and 24.7 +/- 3.0 kg/m2), and waist circumference (94.6 +/- 9.7 and 90.2 +/-
      9.3 cm), were allocated into the groups with (n = 25) and without (n = 98)
      hyperuricemia. The linear regression model, adjusted by HOMA-IR and triglyceride
      levels, showed a significant association of hyperuricemia with both the early
      phase (B = 508.8; 95%CI 253.3-764.4, p<0.001) and late phase of insulin release
      (B = 35.0; 95%CI 8.7-61.3, p = 0.009). CONCLUSIONS: Hyperuricemia is associated
      with the increase of early and late phases of insulin release in apparently
      healthy non-obese subjects with normal glucose tolerance.

PMID- 27045211
TI  - Dengue and chikungunya: modelling the expansion of mosquito-borne viruses into
      naive populations.
AB  - With the recent global spread of a number of mosquito-borne viruses, there is an
      urgent need to understand the factors that contribute to the ability of viruses
      to expand into naive populations. Using dengue and chikungunya viruses as case
      studies, we detail the necessary components of the expansion process: presence of
      the mosquito vector; introduction of the virus; and suitable conditions for local
      transmission. For each component we review the existing modelling approaches that
      have been used to understand recent emergence events or to assess the risk of
      future expansions. We identify gaps in our knowledge that are related to each of
      the distinct aspects of the human-mosquito transmission cycle: mosquito ecology;
      human-mosquito contact; mosquito-virus interactions; and human-virus
      interactions. Bridging these gaps poses challenges to both modellers and
      empiricists, but only through further integration of models and data will we
      improve our ability to better understand, and ultimately control, several
      infectious diseases that exert a significant burden on human health.

PMID- 27045212
TI  - Anniversary issues.

PMID- 27045213
TI  - The philosopher and the engineer.

PMID- 27045215
TI  - Reaction-diffusion processes at the nano- and microscales.
AB  - The bottom-up fabrication of nano- and microscale structures from primary
      building blocks (molecules, colloidal particles) has made remarkable progress
      over the past two decades, but most research has focused on structural aspects,
      leaving our understanding of the dynamic and spatiotemporal aspects at a
      relatively primitive stage. In this Review, we draw inspiration from living cells
      to argue that it is now time to move beyond the generation of structures and
      explore dynamic processes at the nanoscale. We first introduce nanoscale self
      assembly, self-organization and reaction-diffusion processes as essential
      features of cells. Then, we highlight recent progress towards designing and
      controlling these fundamental features of life in abiological systems.
      Specifically, we discuss examples of reaction-diffusion processes that lead to
      such outcomes as self-assembly, self-organization, unique nanostructures,
      chemical waves and dynamic order to illustrate their ubiquity within a unifying
      context of dynamic oscillations and energy dissipation. Finally, we suggest
      future directions for research on reaction-diffusion processes at the nano- and
      microscales that we find hold particular promise for a new understanding of
      science at the nanoscale and the development of new kinds of nanotechnologies for
      chemical transport, chemical communication and integration with living systems. 

PMID- 27045217
TI  - Get the word out.

PMID- 27045216
TI  - Corrigendum: Balancing research and funding using value of information and
      portfolio tools for nanomaterial risk classification.

PMID- 27045218
TI  - Base-Mediated Cyclization Reaction of 2-(5-Hydroxy-1-pentynyl)benzonitriles to 4
      Amino-2,3-dihydronaphtho[2,3-b]furanes and Synthesis of Furanonaphthoquinones.
AB  - An efficient transformation of 2-(5-hydroxy-1-pentynyl)benzonitriles 5 to
      furanonaphthoquinones 11 is presented. Treatment of 5 with 1.5 equiv of NaOMe in
      DMSO at 140  degrees C for 0.5 h gave 6 in good yields. Conversion of 6 to 11 was
      carried out by oxidation of 6 with Fremy's salt and KH2PO4 in acetone and water,
      followed by dehydrogenation using palladium on charcoal in diphenylether at
      reflux temperature.

PMID- 27045219
TI  - Diagnosis of Clinically Significant Portal Hypertension in Patients with
      Cirrhosis: Splenic Arterial Resistive Index versus Liver Stiffness Measurement.
AB  - The purpose of the present study is to compare the diagnostic accuracy of the
      splenic arterial resistive index (SARI) with that of liver stiffness measurement
      (LSM) for identifying patients with clinically significant portal hypertension
      (CSPH). We included 47 patients (M:F = 37:10) who underwent Doppler
      ultrasonography, LSM and hepatic venous pressure gradient (HVPG) on the same day.
      We investigated whether the SARI and LSM were correlated with the HVPG, and
      compared area under the curve (AUC) values for the abilities of SARI and LSM to
      diagnose CSPH. We also performed a sub-group analysis. The SARI and LSM were all
      moderately correlated with HVPG overall in patients. The AUC of SARI and LSM were
      0.873 and 0.745, respectively. In patients without splenomegaly, SARI was
      strongly correlated with HVPG (r = 0.830), but LSM was moderately correlated with
      HVPG (r = 0.601). The AUC was also higher for SARI than for LSM. Therefore, SARI
      is potentially an excellent non-invasive measurement method for diagnosing CSPH,
      especially those without splenomegaly.

PMID- 27045220
TI  - Toxoplasmosis Titers and past Suicide Attempts Among Older Adolescents Initiating
      SSRI Treatment.
AB  - Latent infection with toxoplasmosis is a prevalent condition that has been linked
      in animal studies to high-risk behaviors, and in humans, to suicide and suicide
      attempts. This analysis investigated a relationship between suicide attempt
      history and toxoplasmosis titers in a group of older adolescents who had recently
      begun treatment with an SSRI. Of 108 participants, 17 (15.7 %) had a lifetime
      history of at least one suicide attempt. All were given structured and
      unstructured diagnostic interviews and provided blood samples. Two individuals
      (11.9%) with a past suicide attempt, and two (2.1%) without this history, had
      toxoplasmosis titers >= 10 IU/ml (p = 0.166). Those with a past suicide attempt
      had mean toxoplasmosis titers that were significantly different (p = 0.018) from
      those of patients who lacked this history. An ROC analysis suggested a lower
      optimal threshold for distinguishing patients with and without suicide attempts
      (3.6 IU/ml) than that customarily used to identify seropositivity. Toxoplasmosis
      titers may quantify a proneness to suicidal behavior in younger individuals being
      treated with antidepressants.

PMID- 27045221
TI  - Beyond efficacy and safety-the need for convenient and cost-effective iron
      therapy in health care.
AB  - The National Service Framework advocates correction of anaemia in patients with
      chronic kidney disease (CKD). Oral iron is insufficient, while intravenous (IV)
      supplementation replenishes and maintains iron stores. Previously, effective
      delivery of iron therapy using available parenteral preparations has been
      hampered by dosing schedules and the need in some cases of a test dose. The
      introduction in Europe of newer iron preparations, including iron isomaltoside
      1000 (Monofer) and iron carboxymaltose (Ferinject), now offers a potentially
      safe, effective and time-efficient method of outpatient iron repletion. This may
      potentially lead to better cost-effectiveness in a resource-limited service.

PMID- 27045222
TI  - Clues for divergent, polymorphic amyloidogenesis through dissection of amyloid
      forming steps of bovine carbonic anhydrase and its critical amyloid forming
      stretch.
AB  - Certain amino acid stretches are considered 'critical' to trigger amyloidogenesis
      in a protein. Synthetic peptides corresponding to these stretches are often used
      as experimental mimics for studying the amyloidogenesis of their parent protein.
      Here we provide evidence that such simple extrapolation is misleading. We
      scrutinized each step of amyloid progression of full length bovine carbonic
      anhydrase (BCA) and compared it with the amyloidogenic process of its critical
      peptide stretch 201-227 (PepB). We found that under similar solution conditions
      amyloidogenesis of BCA followed surface-catalyzed secondary nucleation, whereas,
      that of PepB followed classical nucleation-dependent pathway. AFM images showed
      that while BCA formed short, thick and branched fibrils, PepB formed thin, long
      and unbranched fibrils. Structural information obtained by ATR-FTIR spectroscopy
      suggested parallel arrangement of intermolecular beta-sheet in BCA amyloids in
      contrast to PepB amyloids which arranged into antiparallel beta sheets. Amyloids
      formed by BCA were unable to seed the fibrillation of PepB and vice versa. Even
      the intermediates formed during lag phase revealed contrasting FTIR and far UV CD
      signature, hydrophobicity, morphology and cell cytotoxicity. Thus, we propose
      that sequences other than critical amyloidogenic stretches may significantly
      influence the initiation, polymerization and final fibrillar morphology of
      amyloid forming protein. The results have been discussed in light of primary
      sequence mediated amyloid polymorphism and its importance in the rational design
      of amyloid nanomaterials possessing desired physico-chemical properties. 

PMID- 27045223
TI  - The Long-Term Effects of Cancer on Employment and Earnings.
AB  - The study examines long-term effects of cancer on the work status and annual
      earnings of cancer survivors who had a strong attachment to the labor market
      prior to their cancer diagnosis. We use linkage data combining Canadian 1991
      Census microdata with administrative records from the Canadian Cancer Registry,
      the Vital Statistics Registry and longitudinal personal income tax records. We
      estimate changes in the magnitude of cancer effects during the first 3 years
      following the year of the diagnosis using a large sample of cancer survivors
      diagnosed at ages 25 to 61. The comparison group consists of similar workers
      never diagnosed with cancer. The empirical strategy combines coarsened exact
      matching and regression models to deal with observed and unobserved differences
      between the cancer and comparison groups. The results show moderate negative
      cancer effects on work status and annual earnings. Over the 3-year period
      following the year of the diagnosis, the probability of working is 5 percentage
      points lower for cancer survivors than for the comparison group, and their
      earnings are 10% lower. Our findings also suggest that the effects of cancer on
      labor market outcomes differ for high and low survival rate cancer categories.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27045224
TI  - Oculoplastic considerations in patients with glaucoma.
AB  - The incidence of glaucoma worldwide is increasing. Often, these patients may also
      be referred to oculoplastic surgeons for either age-related problems or issues
      secondary to medical or surgical glaucoma treatment. Eyelid malpositions (ptosis
      or lid retraction) may occur after glaucoma filtration surgery or the use of
      prostaglandin analogues. We review the incidence and mechanisms of lid
      malpositions found in the literature. Surgical correction for these malpositions
      also requires careful consideration and should be tailored to the individual
      patient to avoid undesirable surgical outcomes. For instance, overcorrection of
      ptosis may result in bleb exposure and the risk of blebitis or endophthalmitis.
      As use of topical prostaglandin analogues increases, we summarize the reports of
      prostaglandin analogue-associated periocular changes and its underlying etiologic
      mechanisms. Cessation of these medications may be required in some patients.
      Where topical treatment is to be continued, eyelid surgery has to be
      individualized and approached conservatively. It is imperative that patients with
      glaucoma and oculoplastic concerns be considered as a distinct entity to avoid
      unfavorable outcomes.

PMID- 27045225
TI  - Vascular endothelial growth factor and diabetic macular edema.
AB  - Diabetes mellitus is a major global health epidemic, and diabetic macular edema
      is the leading cause of vision loss in this population. Macular focal and/or grid
      laser photocoagulation applied to microaneurysms and thickened retina had long
      been primary therapy for diabetic macular edema. Chronically elevated serum
      glucose is known to cause breakdown in the inner and outer retinal blood barrier
      resulting in upregulation of vascular endothelial growth factor (VEGF).
      Intravitreal anti-vascular endothelial growth factor agents, including
      ranibizumab, bevacizumab, and aflibercept, have been shown in randomized clinical
      trials to be superior to macular laser for the treatment of clinically relevant
      diabetic macular edema. The READ-2, RISE/RIDE, and RESTORE trials established
      ranibizumab's superiority to macular laser, whereas the BOLT trial demonstrated
      bevacizumab's superiority to laser. The DRCR.net Protocol T results showed that
      intravitreal aflibercept, bevacizumab, and ranibizumab were all effective in
      reducing retinal thickness secondary to diabetic edema and in improving vision.
      When the presenting vision was 20/40 or better, visual improvement was
      equivalent. With eyes presenting with 20/50 or worse vision, aflibercept was
      superior with respect to visual improvement. Intravitreal anti-VEGF therapy can
      be burdensome for the patient and health care system, often requiring monthly
      treatment visits. To reduce burdens, anti-VEGF strategies are in development to
      lengthen the treatment interval.

PMID- 27045226
TI  - Ophthalmological manifestations of Parry-Romberg syndrome.
AB  - Parry-Romberg syndrome is a rare disease characterized by slowly progressive
      atrophy affecting facial subcutaneous tissues, including the underlying muscles
      and osteocartilaginous structures. Various periocular, ocular, and neuro
      ophthalmological manifestations have been described in Parry-Romberg syndrome.
      The most common periocular disorders include enophthalmos, eyelid, and orbit
      alterations. The most frequent ocular disorders include corneal and retinal
      changes, and the most common neuro-ophthalmological disorders involve optic
      nerve, ocular motor and pupillary dysfunction. Besides the characteristic facial
      abnormalities, systemic manifestations may occur, including neurologic,
      dermatologic, cardiac, endocrine, infectious, orthodontic, and maxillofacial
      disorders. So far, mainly brief case reports describe these ophthalmological
      findings. Therefore, we summarize the ocular, periocular, and neuro
      ophthalmological findings in detail, describe diagnostic modalities, and outline
      therapeutic options.

PMID- 27045227
TI  - The plausible role of carbonate in photo-catalytic water oxidation processes.
AB  - DFT calculations point out that the photo-oxidation of water on GaN is
      energetically considerably facilitated by adsorbed carbonate. As the redox
      potential of the couple CO3(-)/CO3(2-) is considerably lower than that of the
      couple OH/OH(-) but still enables the oxidation of water it is suggested that
      carbonate should be considered as a catalyst/co-catalyst in a variety of
      catalytic/photo-catalytic/electro-catalytic oxidation processes.

PMID- 27045228
TI  - Chemically Realistic Tetrahedral Lattice Models for Polymer Chains: Application
      to Polyethylene Oxide.
AB  - To speed up the generation of an ensemble of poly(ethylene oxide) (PEO) polymer
      chains in solution, a tetrahedral lattice model possessing the appropriate bond
      angles is used. The distance between noncovalently bonded atoms is maintained at
      realistic values by generating chains with an enhanced degree of self-avoidance
      by a very efficient Monte Carlo (MC) algorithm. Potential energy parameters
      characterizing this lattice model are adjusted so as to mimic realistic PEO
      polymer chains in water simulated by molecular dynamics (MD), which serves as a
      benchmark. The MD data show that PEO chains have a fractal dimension of about
      two, in contrast to self-avoiding walk lattice models, which exhibit the fractal
      dimension of 1.7. The potential energy accounts for a mild hydrophobic effect
      (HYEF) of PEO and for a proper setting of the distribution between trans and
      gauche conformers. The potential energy parameters are determined by matching the
      Flory radius, the radius of gyration, and the fraction of trans torsion angles in
      the chain. A gratifying result is the excellent agreement of the pair
      distribution function and the angular correlation for the lattice model with the
      benchmark distribution. The lattice model allows for the precise computation of
      the torsional entropy of the chain. The generation of polymer conformations of
      the adjusted lattice model is at least 2 orders of magnitude more efficient than
      MD simulations of the PEO chain in explicit water. This method of generating
      chain conformations on a tetrahedral lattice can also be applied to other types
      of polymers with appropriate adjustment of the potential energy function. The
      efficient MC algorithm for generating chain conformations on a tetrahedral
      lattice is available for download at https://github.com/Roulattice/Roulattice . 

PMID- 27045229
TI  - Preoperative Prophylactic Intraaortic Balloon Pump Reduces the Incidence of
      Postoperative Acute Kidney Injury and Short-Term Death of High-Risk Patients
      Undergoing Coronary Artery Bypass Grafting: A Meta-Analysis of 17 Studies.
AB  - This meta-analysis investigated the effects of preoperative prophylactic
      intraaortic balloon pump placement on postoperative renal function and short-term
      death of high-risk patients undergoing coronary artery bypass grafting. We found
      that preoperative prophylactic intraaortic balloon pump support reduced the
      incidence of coronary artery bypass grafting-associated acute kidney injury and
      short-term death and dramatically decreased the incidence of postoperative renal
      replacement therapy by 82% compared with high-risk patients without the
      procedure. This is the first meta-analysis to demonstrate significant beneficial
      effects of preoperative prophylactic intraaortic balloon pump on renal function
      in high-risk patients undergoing coronary artery bypass grafting. 

PMID- 27045230
TI  - Applications to Soft Matter: general discussion.

PMID- 27045231
TI  - Nanomechanical Behavior of High Gas Barrier Multilayer Thin Films.
AB  - Nanoindentation and nanoscratch experiments were performed on thin multilayer
      films manufactured using the layer-by-layer (LbL) assembly technique. These films
      are known to exhibit high gas barrier, but little is known about their
      durability, which is an important feature for various packaging applications
      (e.g., food and electronics). Films were prepared from bilayer and quadlayer
      sequences, with varying thickness and composition. In an effort to evaluate
      multilayer thin film surface and mechanical properties, and their resistance to
      failure and wear, a comprehensive range of experiments were conducted: low and
      high load indentation, low and high load scratch. Some of the thin films were
      found to have exceptional mechanical behavior and exhibit excellent scratch
      resistance. Specifically, nanobrick wall structures, comprising montmorillonite
      (MMT) clay and polyethylenimine (PEI) bilayers, are the most durable coatings.
      PEI/MMT films exhibit high hardness, large elastic modulus, high elastic
      recovery, low friction, low scratch depth, and a smooth surface. When combined
      with the low oxygen permeability and high optical transmission of these thin
      films, these excellent mechanical properties make them good candidates for hard
      coating surface-sensitive substrates, where polymers are required to sustain long
      term surface aesthetics and quality.

PMID- 27045232
TI  - High-Yield Growth and Characterization of ?100? InP p-n Diode Nanowires.
AB  - Semiconductor nanowires are nanoscale structures holding promise in many fields
      such as optoelectronics, quantum computing, and thermoelectrics. Nanowires are
      usually grown vertically on (111)-oriented substrates, while (100) is the
      standard in semiconductor technology. The ability to grow and to control impurity
      doping of ?100? nanowires is crucial for integration. Here, we discuss doping of
      single-crystalline ?100? nanowires, and the structural and optoelectronic
      properties of p-n junctions based on ?100? InP nanowires. We describe a novel
      approach to achieve low resistance electrical contacts to nanowires via a gradual
      interface based on p-doped InAsP. As a first demonstration in optoelectronic
      devices, we realize a single nanowire light emitting diode in a ?100?-oriented
      InP nanowire p-n junction. To obtain high vertical yield, which is necessary for
      future applications, we investigate the effect of the introduction of dopants on
      the nanowire growth.

PMID- 27045233
TI  - Impact of resident involvement in endoscopic bladder cancer surgery on
      pathological outcomes.
AB  - OBJECTIVE: Transurethral resection of bladder tumor (TURBT) pathology specimens
      which lack muscle are associated with clinical upstaging and may necessitate
      repeat resections, potentially delaying curative treatment. This study evaluated
      whether resident involvement in TURBT is associated with suboptimal perioperative
      outcomes. MATERIALS AND METHODS: All TURBTs performed at a Canadian healthcare
      institution from November 2011 to June 2014 were reviewed. Multivariable logistic
      regression models assessed associations between intraoperative resident
      involvement and TURBT muscle presence. Among high-risk patients (high grade, >=
      T1 or carcinoma in situ) who underwent cystectomy, time from TURBT to cystectomy
      was compared between resident and attending urologists with the log-rank test.
      RESULTS: In total, 463 TURBTs were identified. In multivariable analyses,
      residents were less likely to obtain muscle in specimens for all TURBTs [adjusted
      odds ratio (aOR) 0.59, p = 0.03] and the subset of 275 high-risk TURBTs (aOR
      0.41, p = 0.006). Among patients who underwent cystectomy, time to cystectomy was
      delayed by a median of 23 days when residents were involved in the initial high
      risk TURBT compared with attending urologists only (p = 0.024). CONCLUSIONS: In
      this single academic center series, intraoperative resident involvement was
      associated with a decreased rate of muscle presence in TURBT specimens and a
      prolonged time to cystectomy.

PMID- 27045234
TI  - [Kyoto global consensus report for treatment of Helicobacter pylori and its
      implications for China].
AB  - Kyoto global consensus report on Helicobacter pylori gastritis (Gut, July 2015)
      is another important international consensus since the European Maastricht IV
      consensus was published. Kyoto consensus will improve the etiology-based
      classification, the diagnostic assessment of gastritis, and the treatment of H.
      pylori-associated dyspepsia and H. pylori gastritis. However, because of high
      rate of H. pylori infection and antibiotic resistance as well as limited health
      resources in China, we need to develop our own strategies of H. pylori infection
      control with the reference of the Kyoto global consensus.

PMID- 27045235
TI  - [Gastroenteropancreatic neuroendocrine neoplasms: concepts and related issues].
AB  - The incidence of neuroendocrine neoplasms (NENs) has been gradually increasing
      and most of NENs are located in gastroenteropancreatic system. With the
      application of target therapeutic drugs in recent years, the precise pathological
      diagnosis is required critically for effective clinical treatment: target therapy
      needs targeted pathological diagnosis. In this article, the definition of NENs,
      and the century-long evolution of diagnostic terms and grades are reviewed. The
      eight steps of pathological diagnosis of NENs for clinical needs are described.
      Four inconsistent concepts in NENs diagnosis are also discussed, that is
      immunohistochemical biomarkers of pathological diagnosis, subpopulation of
      neuroendocrine neoplasms with high proliferative activity, general
      adenocarcinomas with neuroendocrine differentiation and molecular genetics
      characteristics. To correctly understand these issues would be of great value for
      diagnosis and treatment of NENs. 

PMID- 27045236
TI  - [Classification and clinicopathological characteristics of gastroenteropancreatic
      neuroendocrine neoplasms].
AB  - Gastroenteropancreatic neuroendocrine neoplasms are a rare, heterogeneous group
      of neoplasms. The incidence has increased greatly during the past 40 years,
      partially due to the advanced endoscopic and imaging techniques. As a type of
      neoplasm with the specific morphology and immunophenotype, its nomenclature and
      classification have also been changed considerably over the past 40 years, from
      the past "carcinoid" to the current "neuroendocrine neoplasm". WHO currently
      recommends two-tiered classification, neuroendocrine tumors and neuroendocrine
      cancer, according to the differentiation, morphology and proliferation index.
      However, the neoplasms from different sites have different phenotypes, biological
      behaviors, and accordingly the different staging systems for the indication on
      prognosis and therapy selection. Recent research indicates that the tumor from
      different sites could express different molecular markers which are useful for
      the further study of molecular features, as well as the evaluation of the site of
      primary tumor. Along with the progress of the research on molecular mechanisms,
      including signal transduction, epigenetics and tumor microenviroment, the mode of
      diagnosis and treatment would also be changed accordingly. In this article, new
      advances in classification, clinical and pathological features and molecular
      mechanism of gastroenteropancreatic neuroendocrine neoplasms will be reviewed. 

PMID- 27045237
TI  - [Association of neuroendocrine differentiation with progression and prognosis of
      gastric adenocarcinoma].
AB  - OBJECTIVE: To investigate the association of neuroendocrine differentiation with
      progression and prognosis of gastric adenocarcinoma. METHODS: Clinicopathological
      data of 240 patients with gastric adenocarcinomas were retrospectively analyzed.
      The expression of chromogranin A, synaptophysin and secrectagogin in cancer
      tissue was assessed by immunohistochemistry. The association of neuoroendocrine
      differentiation parameters with disease progression and survival of patients was
      analyzed. RESULTS: The expression of synaptophysin was positively correlated with
      depth of invasion and secretagogin more often expressed in cases with lymph node
      metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and
      secretagogin was unfavorable prognostic predictor. In TNM stage II
      adenocarcinoma, expression of chromogranin A and synaptophysin related to poor
      survival, and multivariate Cox proportional hazard model showed that
      synaptophysin was an independent predictor for poor survival. CONCLUSION:
      Neuroendocrine differentiation predicts deeper depth of invasion, more
      possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.

PMID- 27045238
TI  - [Surgical treatment for pancreatic neuroendocrine neoplasmas].
AB  - Pancreatic neuroendocrine neoplasmas (PNENs) are classified into functioning &
      non-functioning tumors. The radical surgery is the only effective way for the
      cure & long-term survival. For the locoregional resectable tumors, the surgical
      resection is the first choice of treatment; the surgical procedures include local
      resection (enucleation) and standard resection. For the insulinomas and non
      functioning tumors less than 2 cm, local resection (enucleation),distal
      pancreatectomy with spleen-preservation or segmental pancreatectomy are the
      commonly selected procedures. The radical resections with regional lymph nodes
      dissection, including pancreaticoduodenectomy, distal pancreatectomy and middle
      segmental pancreatectomy, should be applied for tumors more than 2 cm or
      malignant ones. For the locoregional advanced or unresectable functioning tumors,
      debulking surgery should be performed and more than 90% of the lesions including
      primary and metastatic tumors should be removed; for the non-functioning tumors,
      if complicated with biliary & digestive tract obstruction or hemorrhage, the
      primary tumors should be resected. The liver is the most frequent site of
      metastases for PNENs and three types of metastases are defined. For
      typeImetastasis, patients are recommended for surgery if there are no
      contraindications; For type II metastasis, debulking surgery should be applied
      and at least 90% of metastatic lesions should be resected, and for patients with
      primary tumors removed and no extrahepatic metastases, or for patients with well
      differentiated (G1/G2) tumors, liver transplantation may be indicated. For the
      unresectable type III metastasis, multiple adjuvant therapies should be chosen.

PMID- 27045239
TI  - [Update of pathological diagnosis of pulmonary neuroendocrine tumor].
AB  - Pulmonary neuroendocrine tumors are common in pathological practice and its
      pathological classification and histological grading are not exactly the same as
      that of those in the digestive tract and pancreas. In 2015 edition of World
      Health Organization classification, pulmonary neuroendocrine tumors are
      classified as carcinoid tumors (including typical carcinoid and atypical
      carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and
      precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each
      category has distinctive morphological and immunohistochemical features. The
      morphologic features including growth patterns and cytological appearances are
      keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings
      are also critical for its diagnosis. Furthermore, the diagnostic criteria vary
      for different types of specimen. In this article, we present a concise review and
      summary of the update of clinicopathological characterizations of pulmonary
      neuroendocrine tumor, with an emphasis on its diagnostic criteria and
      differential diagnosis. 

PMID- 27045240
TI  - [Neuroendocrine differentiation and Wilms' tumor protein-1 expression in breast
      mucinous carcinoma and their significance].
AB  - OBJECTIVE: To investigate neuroendocrine differentiation and Wilms' tumor protein
      1 (WT-1) expression in breast mucinous carcinoma and their clinicopathological
      significance. METHODS: The clinicopathological data of 65 patients with breast
      mucinous carcinoma, including 31 cases of mixed mucinous carcinoma, 23 cases of
      hypocellular pure mucinous carcinoma and 11 cases of hypercellular pure mucinous
      carcinoma, admitted in Taizhou Hospital from January 2010 to June 2015 were
      retrospectively reviewed. The expression of neuroendocrine markers and WT-1 was
      detected by immunohistochemistry staining in all cases. RESULTS: The mixed
      mucinous carcinomas and hypercelluar pure mucinous carcinomas had higher
      incidence of axillary lymph node metastasis and human epidermal recepter 2 (HER
      2) positive than hypocellular pure mucinous carcinoma (all (P<0.01). However, the
      difference was not significant between mixed mucinous carcinomas and
      hypercellular pure mucinous carcinomas (all P>0.05). The expression of
      neuroendocrine marker was stronger in hypercellular mucinous carcinoma than that
      in mixed mucinous carcinoma and hypocellular mucinous carcinoma (all (P<0.05),
      but the difference was not statistically significant between mixed mucinous
      carcinoma and hypocellular pure mucinous carcinoma (P>0.05). The expression of WT
      1 was weaker in mixed mucinous carcinoma than that in hypercellular and
      hypocellular pure mucinous carcinoma(all (P<0.05), but the difference was not
      statistically significant between hypercellular and hypocellular pure mucinous
      carcinoma (P>0.05). The mucinous carcinomas with lymph node metastasis had lower
      expression of neuroendocrine markers than those without lymph node metastasis
      ((P<0.01). The expression of WT-1 in breast mucinous carcinoma with lymph node
      metastasis trended lower than that in those without lymph node metastasis, but
      the difference was not statistically significant (P>0.05). CONCLUSION:
      Hypercellular pure mucinous breast carcinoma has higher rates of lymph node
      metastasis and HER-2 amplification than hypocellular pure mucinous carcinoma, the
      sub-classification of breast pure mucinous carcinoma should be considered.
      Neuroendocrine differentiation and WT-1 expression may be helpful in
      distinguishing the subtypes of breast mucinous carcinoma. Breast mucinous
      carcinoma with neuroendocrine differentiation trends to have less lymph node
      metastasis.

PMID- 27045241
TI  - [The state of the art of imaging in gastroenteropancreatic neuroendocrine
      tumors].
AB  - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are neoplasms presenting
      unpredictable and unusual biologic behavior that causes many clinical challenges.
      NETs can produce a variety of metabolically active substances (hormones and
      amines) leading to distinct clinical syndromes. This review will discuss the
      imaging techniques for the diagnosis of GEP-NETs including ultrasonography, CT,
      MRI and ultrasound endoscope. In this article, Gallium-68 labeled peptide binding
      to G protein coupled receptor including SSTR, CCKR1 and GLP1R is addressed, and
      the application of Gallium-68 labeled somatostin analogues and PET-CT for
      diagnosis of GEP-NETs is evaluated. In conclusion, Gallium-68 labeled peptide and
      molecular imaging will play important roles in diagnosis, prognosis and
      therapeutic strategy development of GEP-NETs.

PMID- 27045242
TI  - [Location and functions of secretagogin protein].
AB  - Secretagogin (SCGN) is a novel member of EF-hand Ca2+-binding proteins, which was
      identified in islet beta cells by Wagner. SCGN is a six EF-hand Ca2+-binding
      protein, primarily expressed on the neuroendocrine axis and the central nervous
      system. The protein has abundant biological functions. A certain concentration of
      calcium ion can lead to conformation change of SCGN, resulting in the change of
      intracellular signal transduction. Preliminary studies showed that SCGN would be
      used to treat stress reaction, such as mental illness (depression), burns or post
      traumatic stress disorder and chronic stress reaction caused by pain. In
      Alzheimer's disease, the expression of SCGN in the hippocampus can boycott
      neurodegeneration. In neuroendocrine tumors, SCGN presents a good consistency
      with neuroendocrine markers such as CgA, Syn, and NSE, with a higher overall
      sensitivity and specificity. In addition, SCGN is released into serum after
      neural damage in cerebral ischemic diseases, suggesting that SCGN can be used as
      a marker for brain trauma. In this article, we review the recent research
      progress of secretagogin, focus on its distribution and functions in various
      tumorous diseases and non-tumorous diseases, such as Alzheimer's disease.

PMID- 27045243
TI  - [Establishment and preliminary application of detection of Mycobacterium
      tuberculosis in sputum based on variable number tandem repeat].
AB  - OBJECTIVE: To establish a laboratory method for detection of Mycobacterium
      tuberculosis in sputum based on variable number tandem repeat (VNTR). METHODS:
      Mycobacterium tuberculosis was tested by VNTR and fluorescent quantitative
      reverse transcription polymerase chain reaction (FQ-PCR) in 130 sputum samples
      from patients with pulmonary tuberculosis and 200 specimens from patients with
      other lung diseases. According to the amplification conditions and clinical
      detection needs, MTUB21, MUTB04, QUB18, QUB26, QUB11b, MIRU31, MIRU10 and MIRU26
      were selected as test targets. The results of VNTR and FQ-PCR were compared with
      Lowenstein-Jensen culture and clinical diagnosis, and analyzed by chi-square
      test. RESULTS: With the results of L-J culture as the standard, the sensitivity
      and specificity of VNTR were 93.1% (108/116) and 97.7% (209/214), and those of FQ
      PCR were 94.0% (109/116) and 96.7% (207/214), respectively; no significant
      difference was observed between two groups (chi2=0.352, P=0.569). Using the
      clinical diagnosis as the standard, the sensitivity and specificity of VNTR were
      86.9% (113/130) and 100% (200/200), and those of FQ-PCR were 87.7% (114/130) and
      99.0% (198/200), respectively; the difference was not statistically significant
      (chi2=0.030, P=0.862). In 113 VNTR positive samples, the molecular codes differed
      from each other in 98.2% samples (111/113); only 2 samples had identical code (5
      4-6-8-5-5-3-8). CONCLUSION: The study suggests that VNTR provides a promising
      method for diagnosis of clinical tuberculosis.

PMID- 27045244
TI  - [Overexpression of PPARgamma induces adipogenic steatosis in mouse primary
      hepatocytes].
AB  - OBJECTIVE: To investigate the effects of PPARgamma overexpression on steatosis in
      mouse primary hepatocytes. METHODS: Primary hepatocytes isolated from C57BL/6J
      mice were infected with either Ad/LacZ or Ad/PPARgamma for 48 h. Steatosis of the
      primary hepatocytes was checked by Oil Red O staining. The mRNA and protein
      expression of adipocyte-specific genes PPARgamma, aP2 and CideA were analyzed by
      using RT Real-time PCR and Western Blot. RESULTS: Primary hepatocytes were small
      and even. Hepatocyte nuclei were round with dispersed chromatin and prominent
      nucleoli. Accumulated lipid droplets were observed in Ad/PPARgamma-infected
      hepatocytes, but in Ad/LacZ-infected hepatocytes. Moreover, compared with Ad/LacZ
      infected hepatocytes, the mRNA expression of PPARgamma, aP2, FGF21 and CideA in
      Ad/PPARgamma-infected hepatocytes were significantly induced, the protein
      expression of PPARgamma and its target aP2 strongly increased. CONCLUSION: over
      expression of PPARgamma induces adipogenic steatosis in mouse primary
      hepatocytes.

PMID- 27045245
TI  - [Comparison of characteristics of esophageal gastric varices in portal
      hypertension patients with and without spontaneous shunts].
AB  - OBJECTIVE: To compare the characteristics of esophageal gastric varices in portal
      hypertension patients with and without spontaneous shunts. METHODS: Clinical data
      of 118 patients with esophageal gastric varices undergoing portal vein computed
      tomographic angiography (CTA) and gastroscopy between January 2012 and August
      2015 was retrospectively reviewed. RESULTS: Portal vein CTA results showed that
      spleno-renal or gastro-renal shunts were detected in 24 out of 118 cases. The
      average portal vein diameters (PVD) of patients with and without spontaneous
      shunt were (12.48+/-2.79) mm and (13.58+/-3.46) mm, respectively (P>0.05). The
      average area of gastric veins in patients with spontaneous shunt was
      significantly larger than that of patients without shunt [294.00 (0.00~2400.00)
      mm2 vs. 26.00 (0.00~1620.00) mm2, respectively, (P<0.001]. Compared with patients
      without spontaneous shunt, the location of esophageal varices was lower and the
      degree was less serious in patients with spontaneous shunt (P<0.05). No matter
      with history of uppergastrointestinal bleeding, the average area of gastric veins
      in patients with spontaneous shunt was significantly larger than that of patients
      without shunt (P<0.05). For patients having no history of splenectomy, the
      average portal vein diameter (PVD) in those with spontaneous shunt was
      significantly smaller than that in those without shunt (P<0.05). CONCLUSION: The
      portal vein diameter of patients without splenectomy and with spontaneous shunts
      is shorter and their esophageal varices are less serious; the gastric veins are
      large and wriggly in patients with spontaneous shunts.

PMID- 27045246
TI  - [Platelet count predicts therapeutic response of infliximab for active Crohn's
      disease].
AB  - OBJECTIVE: To explore the platelet count in prediction of the efficacy of
      infliximab for active Crohn's disease. METHODS: A total of 74 patients with
      Crohn's disease, including 50 males and 24 females with mean age of 27 years,
      receiving infliximab therapy from January 2011 to June 2015 were retrospectively
      included. Clinical variables including routine blood test, erythrocyte
      sedimentation rate, C-reactive protein and Crohn's disease activity index were
      measured before treatment and after 3rd, 6th treatments. RESULTS: Compared with
      baseline, the Crohn's disease activity index score, white blood cell count,
      platelet count, erythrocyte sedimentation rate, C-reactive protein significantly
      decreased (all (P<0.01), while hemoglobin and red blood cell hematocrit increased
      (P<0.01) in patients after 3 treatments of infliximab. These variables were
      further improved after 6 treatments. Further analysis showed that platelet count
      was positively associated with disease severity of Crohn's disease. Fifty-three
      patients achieved clinical remission (Crohn's disease activity index score<150)
      after 3 treatments of infliximab. Logistic regression analysis showed that
      baseline platelet count, Crohn's disease activity index, and disease course were
      three predictors for clinical remission of Crohn's disease. CONCLUSION: Platelet
      count is positively associated with disease severity of Crohn's disease, and
      baseline platelet count is an important predicator for the early response of
      infliximab therapy.

PMID- 27045247
TI  - [Transcatheter delivery of recombinant adenovirus vector containing exogenous
      aquaporin gene in treatment of Sjogren's syndrome].
AB  - Sjogren's syndrome is a kind of autoimmune disease, whose main clinical symptoms
      are dry mouth, dry eye and chronic parotid glandular inflammation. The
      conservative treatments include artificial tears or saliva,oral administration of
      corticosteroids,and immunosuppressantsl with limited effectiveness. Along with
      the development of molecular biology, vast attentions are being paid to
      researches on gene therapy for Sjogren's syndrome, hopefully to bring gospel to
      patients with Sjogren's syndrome. This article reviews the recent research
      progresses on transcatheter delivery of recombinant adenovirus vector with
      aquaporin gene in experimental treatment of Sjogren's syndrome. 

PMID- 27045248
TI  - [Molecular biological foundation of targeted therapy for metastatic renal cell
      carcinoma].
AB  - The incidence of renal cell carcinoma (RCC) is increasing. Radical cure by
      surgery can only be achieved in patients with early stage tumors. How to
      precisely use antineoplastic agents after surgery is an important problem to be
      solved. Most metastatic RCCs are pathologically identified as clear cell RCC
      (ccRCC), thus to develop agents targeting ccRCC is critical. Most clinically
      available targeted therapies are based on targeting some spots in specific
      pathways; or based on targeting new anti-tumor mechanisms, such as programmed
      death-1(PD-1), antibody-drug conjugates (ADC) and stem cells. There is still no
      targeted therapy having definite effect to most RCC patients. Only von Hippel
      Lindau (VHL) pathway so far has been confirmed to be related to ccRCC development
      and progression; the inactivation of VHL gene causes many significant downstream
      gene changes. The key proteins involved in VHL pathway may be potential
      therapeutic targets for ccRCC. In this article, we review the current progress of
      targeted therapy for RCC, focus on the molecular characteristics of ccRCC, its
      relation to VHL pathway, the potential therapeutic targets and future clinical
      application for metastatic ccRCC. 

PMID- 27045249
TI  - [Frontiers of research on nonalcoholic fatty liver disease].

PMID- 27045250
TI  - Multistakeholder recommendations for improving value of spine care: Key themes
      from a roundtable discussion at the 2015 NASS Annual Meeting.

PMID- 27045251
TI  - Regional variations in spine surgery: current challenges and potential solutions.

PMID- 27045252
TI  - Comparative study of the efficacy of limaprost and pregabalin as single agents
      and in combination for the treatment of lumbar spinal stenosis: a prospective,
      double-blind, randomized controlled non-inferiority trial.
AB  - BACKGROUND CONTEXT: Although the simultaneous management of neuronal ischemia
      related pain and compression-demyelination-related neuropathic pain is considered
      optimal in treating lumbar spinal stenosis (LSS), the effect of combination
      therapy with pregabalin and limaprost has not been elucidated. PURPOSE: This
      study aimed to compare the effects of limaprost and pregabalin individually and
      in combination for the treatment of LSS. STUDY DESIGN: This is a prospective,
      double-blind, double-dummy, randomized controlled trial. PATIENT SAMPLE: The
      sample consists of patients with LSS. OUTCOME MEASURES: The baseline-adjusted
      Oswestry Disability Index (ODI) score, visual analog scale (VAS) scores for leg
      pain, the European Quality of Life-5 dimensions (EQ-5D), and initial claudication
      distance (ICD). METHODS: The present study (ClinicalTrials.gov, number
      NCT01888536) was a prospective, double-blind, double-dummy, randomized controlled
      trial designed to determine the efficacy of limaprost in alleviating leg pain,
      improving disability, and increasing walking distance in persons with
      degenerative LSS in three different treatment groups: limaprost alone, pregabalin
      alone, and combined limaprost and pregabalin through 1:1:1 allocation. The
      primary outcome was the baseline-adjusted ODI score at 8 weeks after treatment.
      The non-inferior margin of the ODI was set at delta=10 points. RESULTS: The
      baseline-adjusted ODI score (primary outcome) at 8 weeks after treatment in the
      limaprost group was not inferior to those in the pregabalin and
      limaprost+pregabalin groups. The overall changes of the baseline-adjusted ODI
      scores, VAS scores for leg pain, the EQ-5D, and ICD during the follow-up
      assessments over an 8-week period (secondary end point) were not different among
      the three groups. The baseline-adjusted ODI scores and VAS scores for leg pain
      decreasedsignificantly over time after treatment in all three groups. The
      baseline-adjusted EQ-5D score and ICD also increased significantly over time
      after treatment in all three groups. CONCLUSIONS: The efficacy of limaprost for
      lumbar spinal stenosis was not inferior compared with that of pregabalin or the
      combination of limaprost and pregabalin in terms of disability. Therefore,
      combined treatment with limaprost and pregabalin does not provide additional
      relief in symptoms in patients with LSS compared with monotherapy with limaprost
      or pregabalin.

PMID- 27045253
TI  - Improving the physico-chemical and sensory characteristics of camel meat burger
      patties using ginger extract and papain.
AB  - The objective of the current study was to include tenderizing agents in the
      formulation of camel meat burger patties to improve the physico-chemical and
      sensory characteristics of the product. Camel meat burger patties were processed
      with addition of ginger extract (7%), papain (0.01%) and mixture of ginger
      extract (5%) and papain (0.005%) in addition to control. Addition of ginger,
      papain and their mixture resulted in significant (P<0.05) increase of the
      collagen solubility and sensory scores (juiciness, tenderness and overall
      acceptability) with significant (P<0.05) reduction of the shear force values.
      Ginger extract resulted in extensive fragmentation of myofibrils; however, papain
      extract caused noticeable destructive effect on connective tissue. Moreover,
      ginger and papain resulted in improvement of the lipid stability of treated
      burger patties during storage. Therefore, addition of ginger extract and papain
      powder during formulation of camel burger patties can improve their physico
      chemical and sensory properties. 

PMID- 27045254
TI  - Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth
      International Consultation for Sexual Medicine (ICSM 2015).
AB  - INTRODUCTION: Treatment of erectile dysfunction is based on pharmacotherapy for
      most patients. AIM: To review the current data on pharmacotherapy for erectile
      dysfunction based on efficacy, psychosocial outcomes, and safety outcomes.
      METHODS: A review of the literature was undertaken by the committee members. All
      related articles were critically analyzed and discussed. MAIN OUTCOME MEASURES:
      Levels of evidence (LEs) and grades of recommendations (GRs) are provided based
      on a thorough analysis of the literature and committee consensus. RESULTS: Ten
      recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are
      effective, safe, and well-tolerated therapies for the treatment of men with
      erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences
      in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A).
      (iii) PDE5 inhibitors are first-line therapy for most men with erectile
      dysfunction who do not have a specific contraindication to their use (LE = 3, GR
      = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and
      well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v)
      Intracavernosal injection therapy with alprostadil should be offered to patients
      as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi)
      Intraurethral and topical alprostadil are effective and well-tolerated treatments
      for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and
      topical alprostadil should be considered second-line therapy for erectile
      dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5
      inhibitors to the maximum tolerated dose is strongly recommended because it
      increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix)
      Treatment selection and follow-up should address the psychosocial profile and the
      needs and expectations of a patient for his sexual life. Shared decision making
      with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x)
      Counterfeit medicines are potentially dangerous. It is strongly recommended that
      physicians educate their patients to avoid taking any medication from
      unauthorized sources (LE = 2, GR = A). The first seven recommendations are the
      same as those from the Third International Consultation for Sexual Medicine and
      the last three are new recommendations. CONCLUSION: PDE5 inhibitors remain a
      first-line treatment option because of their excellent efficacy and safety
      profile. This class of drugs is continually developed with new molecules and new
      formulations. Intracavernosal injections continue to be an established treatment
      modality, and intraurethral and topical alprostadil provide an alternative, less
      invasive treatment option.

PMID- 27045255
TI  - Penile Prosthesis Surgery: Current Recommendations From the International
      Consultation on Sexual Medicine.
AB  - INTRODUCTION: Penile prosthesis implantation has emerged as a definitive
      treatment to restore sexual function to the motivated man with erectile
      dysfunction. Substantial improvements in the design of inflatable devices have
      been made since they first became available more than four decades ago. AIM: To
      review the history of the penile prosthesis, the indications, preoperative
      evaluation, and patient and partner satisfaction. The current approaches to
      addressing intra- and postoperative complications, provide an understanding of
      prosthesis infection, and placement of these devices will be reviewed. METHODS: A
      committee of worldwide experts in this field was assembled during the 2015
      International Consultation on Sexual Medicine (ICSM) and performed a systematic
      review of the peer-reviewed published medical literature pertaining to penile
      prosthesis. Particular attention was given to higher level trials when available.
      Recommendations are based upon the Oxford Criteria. MAIN OUTCOME MEASURES:
      Unfortunately there is limited level 1 and 2 evidence, and where expert opinion
      was utilized, the decision was unanimous within the committee with a goal of
      presenting a clinically relevant guideline pertaining to penile prostheses.
      RESULTS: Penile prosthesis has undergone an evolution over the past 40 years
      resulting in a more effective and reliable treatment for advanced erectile
      dysfunction not responding to less invasive methods including oral treatment with
      PDE5 inhibitors, vacuum erection device, and intracorporal injection therapy. It
      should be considered an appropriate treatment option for the man who wishes to
      restore erectile function and who understands the potential risk of mechanical
      failure and infection, both of which are less common now as a result of
      improvements made in device design as well as surgical protocols adhered to in
      the operating room. Patients must be clearly informed of the risks associated
      with penile prosthesis including mechanical failure, infection, shortening of the
      penis, change in sensation and configuration of the penis, as well as injury to
      local structures. Intraoperative complications are unusual but do occur and can
      usually be addressed intraoperatively to allow placement of the device at the
      time of initial surgery. Postoperative complications may also be addressed when
      they occur but may require more advanced reconstructive surgical techniques. Men
      with Peyronie's disease, corporal fibrosis due to infection, trauma, prior
      prosthesis explantation, priapism, and men who have undergone construction of a
      neophallus may require additional advanced maneuvers to obtain optimum results
      with a penile prosthesis. CONCLUSION: Penile prosthesis remains as an important,
      viable, and effective treatment for male erectile dysfunction that does not
      respond to other less invasive approaches or when these approaches are
      contraindicated or not acceptable to the patient. These devices provide the
      patient with the ability to engage in penetrative sexual activity without
      interfering with urination, ejaculation, sensation, or orgasm. Although
      mechanical failure can occur, the current devices are more reliable as a result
      of design modifications. Infection remains the most dreaded complication but
      since the introduction of antibiotic and hydrophilic coatings, infection is less
      common. Overall, patient and partner satisfaction appear to be reasonably high
      when a penile prosthesis is used to restore erectile function.

PMID- 27045256
TI  - Cancer, Benign Gynecology, and Sexual Function--Issues and Answers.
AB  - INTRODUCTION: The diagnosis, treatment, and survivorship of cancer have a
      profound effect on the quality of life and psychological well-being of men and
      women. Indeed, the perturbation of sexual function because of neoplasm has far
      reaching implications. AIMS: To explore the prevalence, pathophysiology, and
      treatment of sexual issues in persons with cancer and offer evidence-based
      recommendations regarding optimal prevention and treatment strategies. METHODS: A
      committee of multidisciplinary specialists was formed as part of the larger
      International Sexual Medicine Consultation working with urologic and sexual
      medicine societies over a 1-year period to review the result of chronic-illness
      management on sexual function and satisfaction. The aims, goals, data collection
      techniques, and report format were defined by a central committee. MAIN OUTCOMES
      MEASURES: Expert consensus was based on evidence-based medical and psychosocial
      literature review, extensive group discussion, and an open presentation with a
      substantial discussion period. RESULTS: This summary evaluates contemporary
      literature concerning the prevalence, pathophysiology, and psychological impact
      of cancer diagnosis and treatment on sexual dysfunction. Evidence-based
      recommendations and guidelines for evaluation and management are presented.
      CONCLUSION: The diagnosis and treatment of cancer have a significant negative
      impact on sexual function and satisfaction. Comprehension of baseline sexual
      function, role of psychological supports, and available treatment options could
      attenuate the heavy burden of decreased sexual function.

PMID- 27045257
TI  - Psychological and Interpersonal Dimensions of Sexual Function and Dysfunction.
AB  - INTRODUCTION: Psychological, interpersonal, and sociocultural factors play a
      significant role in making one vulnerable to developing a sexual concern, in
      triggering the onset of a sexual difficulty, and in maintaining sexual
      dysfunction in the long term. AIM: To focus on psychological and interpersonal
      aspects of sexual functioning in women and men after a critical review of the
      literature from 2010 to the present. METHODS: This report is part 1 of 2 of our
      collaborative work during the 2015 International Consultation on Sexual Medicine
      for Committee 2. MAIN OUTCOME MEASURES: Systematic review of the literature with
      a focus on publications since 2010. RESULTS: Our work as sexual medicine
      clinicians is essentially transdisciplinary, which involves not only the
      collaboration of multidisciplinary professionals but also the integration and
      application of new knowledge and evaluation and subsequent revision of our
      practices to ensure the highest level of care provided. There is scant literature
      on gender non-conforming children and adolescents to clarify specific
      developmental factors that shape the development of gender identity, orientation,
      and sexuality. Conversely, studies consistently have demonstrated the
      interdependence of sexual function between partners, with dysfunction in one
      partner often contributing to problems in sexual functioning and/or sexual
      satisfaction for the other. We recommend that clinicians explore attachment
      styles of patients, childhood experiences (including sexual abuse), onset of
      sexual activity, personality, cognitive schemas, infertility concerns, and sexual
      expectations. Assessment of depression, anxiety, stress, substance use and post
      traumatic stress (and their medical treatments) should be carried out as part of
      the initial evaluation. Clinicians should attempt to ascertain whether the
      anxiety and/or depression is a consequence or a cause of the sexual complaint,
      and treatment should be administered accordingly. Cognitive distraction is a
      significant contributor to sexual response problems in men and women and is
      observed more consistently for genital arousal than for subjective arousal.
      Assessment of physical and mental illnesses that commonly occur in later life
      should be included as part of the initial evaluation in middle-aged and older
      persons presenting with sexual complaints. Menopausal status has an independent
      effect on reported changes in sex life and difficulties with intercourse. There
      is strong support for the use of psychological treatment for sexual desire and
      orgasm difficulties in women (but not in men). Combination therapies should be
      provided to men, whenever possible. CONCLUSION: Overall, research strongly
      supports the routine clinical investigation of psychological factors, partner
      related factors, context, and life stressors. A biopsychosocial model to
      understand how these factors predispose to sexual dysfunction is recommended.

PMID- 27045258
TI  - Vulvodynia: Assessment and Treatment.
AB  - INTRODUCTION: Vulvodynia constitutes a highly prevalent form of sexual pain in
      women, and current information regarding its assessment and treatment is needed.
      AIM: To update the scientific evidence published in 2010, from the Third
      International Consultation on Sexual Medicine, pertaining to the assessment and
      treatment of women's sexual pain. METHODS: An expert committee, as part of the
      Fourth International Consultation on Sexual Medicine, was comprised of
      researchers and clinicians from biological and social science disciplines for the
      review of the scientific evidence on the assessment and treatment of women's
      genital pain. MAIN OUTCOME MEASURES: A review of assessment and treatment
      strategies involved in vulvodynia. RESULTS: We recommend the following treatments
      for the management of vulvodynia: psychological interventions, pelvic floor
      physical therapy, and vestibulectomy (for provoked vestibulodynia). We also
      support the use of multidisciplinary treatment approaches for the management of
      vulvodynia; however, more studies are needed to determine which components are
      most important. We recommend waiting for more empirical evidence before
      recommending alternative treatment options, anti-inflammatory agents, hormonal
      agents, and anticonvulsant medications. Although we do not recommend lidocaine,
      topical corticosteroids, or antidepressant medication for the management of
      vulvodynia, we suggest that capsaicin, botulinum toxin, and interferon be
      considered second-line avenues and that their recommendation be revisited once
      further research is conducted. CONCLUSION: A comprehensive assessment is needed
      to understand the pain experience of women presenting with vulvodynia. In
      addition, treatment typically progresses from less invasive to more invasive, and
      several treatment options are worth pursuing.

PMID- 27045259
TI  - Ethical and Sociocultural Aspects of Sexual Function and Dysfunction in Both
      Sexes.
AB  - AIMS: This study aimed to highlight the salient sociocultural factors
      contributing to sexual health and dysfunction and to offer recommendations for
      culturally sensitive clinical management and research as well for an ethically
      sound sexual health care, counseling and medical decision-making. BACKGROUND:
      There are limited data on the impact of sociocultural factors on male and female
      sexual function as well as on ethical principles to follow when clinical care
      falls outside of traditional realms of medically indicated interventions.
      METHODS: This study reviewed the current literature on sociocultural and ethical
      considerations with regard to male and female sexual dysfunction as well as
      cultural and cosmetic female and male genital modification procedures. RESULTS:
      It is recommended that clinicians evaluate their patients and their partners in
      the context of culture and assess distressing sexual symptoms regardless of
      whether they are a recognized dysfunction. Both clinicians and researchers should
      develop culturally sensitive assessment skills and instruments. There are a
      number of practices with complex ethical issues (eg, female genital cutting,
      female and male cosmetic genital surgery). Future International Committee of
      Sexual Medicine meetings should seek to develop guidelines and associated
      recommendations for a separate, broader chapter on ethics.

PMID- 27045260
TI  - 2015 ISSVD, ISSWSH, and IPPS Consensus Terminology and Classification of
      Persistent Vulvar Pain and Vulvodynia.
AB  - INTRODUCTION: In 2014, the Executive Council of the International Society for the
      Study of Vulvovaginal Disease (ISSVD), the Boards of Directors of the
      International Society for the Study of Women's Sexual Health (ISSWSH), and the
      International Pelvic Pain Society (IPPS) acknowledged the need to revise the
      current terminology of vulvar pain, based on the significant increase in high
      quality etiologic studies published in the last decade. METHODS: The new
      terminology was achieved in four steps. The first involved a terminology
      consensus conference with representatives of the three societies, held in April
      2015. Then, an analysis of the relevant published studies was used to establish a
      level of evidence for each factor associated with vulvodynia. The terminology was
      amended based on feedback from members of the societies. Finally, each society's
      board accepted the new terminology. RESULTS AND CONCLUSION: In 2015, the ISSVD,
      ISSWSH, and IPPS adopted a new vulvar pain and vulvodynia terminology that
      acknowledges the complexity of the clinical presentation and pathophysiology
      involved in vulvar pain and vulvodynia, and incorporates new information derived
      from evidence-based studies conducted since the last terminology published in
      2003.

PMID- 27045261
TI  - Prevalence of Transgender Depends on the "Case" Definition: A Systematic Review.
AB  - INTRODUCTION: A systematic review and meta-analysis was conducted to evaluate how
      various definitions of transgender affect prevalence estimates. AIMS: To evaluate
      the epidemiology of transgender and examine how various definitions of
      transgender affect prevalence estimates and to compare findings across studies
      that used different methodologies, in different countries, and over different
      periods. METHODS: PubMed, EMBASE, and Medline were searched to identify studies
      reporting prevalence estimates of transgender in a population. All studies were
      grouped based on the case definition applied to the numerator. Summary estimates
      were derived using a random-effects model for total prevalence of transgender and
      for male-to-female and female-to-male subgroups. Overall and stratum-specific
      meta-prevalence estimates (mPs) and 95% confidence intervals (CIs) were
      accompanied by tests for heterogeneity and meta-regressions to assess sources of
      heterogeneity. MAIN OUTCOME MEASURES: The main outcome measure was population
      prevalence of transgender. Secondary outcomes included gender-specific prevalence
      estimates for male-to-female and female to male subgroups. RESULTS: Thirty-two
      studies met the inclusion criteria for systematic review. Of those, 27 studies
      provided necessary data for a meta-analysis. Overall mP estimates per 100,000
      population were 9.2 (95% CI = 4.9-13.6) for surgical or hormonal gender
      affirmation therapy and 6.8 (95% CI = 4.6-9.1) for transgender-related diagnoses.
      Of studies assessing self-reported transgender identity, the mP was 871 (95% CI =
      519-1,224); however, this result was influenced by a single outlier study. After
      removal of that study, the mP changed to 355 (95% CI = 144-566). Significant
      heterogeneity was observed in most analyses. CONCLUSION: The empirical literature
      on the prevalence of transgender highlights the importance of adhering to
      specific case definitions because the results can range by orders of magnitude.
      Standardized and routine collection of data on transgender status and gender
      identity is recommended.

PMID- 27045262
TI  - Sexual Difficulties and Associated Sexual Distress in Flanders (Belgium): A
      Representative Population-Based Survey Study.
AB  - INTRODUCTION: Because severity and duration of sexual impairment and any distress
      caused by the sexual impairment are not assessed in most epidemiologic studies on
      sexual dysfunction, the available prevalence rates are probably an
      overestimation. AIMS: To provide prevalence estimates of severe and persistent
      sexual difficulties that cause personal distress and to explore the association
      between personal sexual distress and avoidance of sex, help-seeking behavior, and
      sexual satisfaction. METHODS: This study used home-based computer-assisted
      personal interviewing and computer-assisted self-interviewing of a
      representative, randomly selected, population-based cross-sectional sample of 651
      Flemish men and 695 women 14 to 80 years old. MAIN OUTCOME MEASURES: Prevalence
      of sexual difficulties, prevalence of sexual dysfunctions (ie, sexual
      difficulties causing personal distress), and association of sexual distress with
      avoidance of sex, help-seeking behavior, and sexual satisfaction. RESULTS: In
      this sample, 43.5% of women (95% CI =39.7-47.3) and 34.8% of men (95% CI =31.3
      38.3) reported a moderate to severe sexual difficulty. When considering the
      diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (ie, minimum duration of 6 months and presence of personal sexual
      distress), prevalence rates decreased to 19.0% in women (95% CI =16.0-22.0) and
      to 15.1% in men (95% CI =12.4-17.8). Sexual distress was associated with more
      sexual dissatisfaction and greater sexual avoidance. Sexual distress also was
      associated with help-seeking behavior, although most individuals with distressing
      sexual difficulties had not sought help. CONCLUSION: Although sexual difficulties
      per se are quite prevalent, severe and persistent sexual difficulties causing
      sexual distress are far less common. Despite sexual distress being associated
      with avoidance of sex and lower sexual satisfaction, most people tend not to seek
      help for their sexual problem, even when being distressed by the problem.

PMID- 27045263
TI  - Erectile Function Recovery After Nerve-Sparing Radical Prostatectomy for Prostate
      Cancer: Is Back to Baseline Status Enough for Patient Satisfaction?
AB  - INTRODUCTION: Several definitions of erectile function (EF) recovery after
      bilateral nerve-sparing radical prostatectomy (BNSRP) have been proposed based on
      the results of the International Index of EF (IIEF). AIM: We aimed at evaluating
      overall satisfaction (OS) after BNSRP according to the ability to achieve the
      pretreatment EF. METHODS: We evaluated data of 652 patients treated with BNSRP
      for clinically localized prostate cancer (PCa). Erectile dysfunction (ED) was
      classified according to the IIEF-EF domain score. Return to baseline EF was
      defined as patients who reached the same preoperative ED category during the 3
      year follow-up. Cox regression analyses were fitted to predict return to baseline
      IIEF-EF and to predict OS defined according to the IIEF-OS in the overall
      population. Logistic regression analyses were performed to analyze OS in men who
      reached the back to baseline status. MAIN OUTCOME MEASURES: The outcome of the
      study was to evaluate back to baseline EF status and to correlate it with
      postoperative OS. RESULTS: Preoperative satisfaction was reported by 218 (33.4%)
      patients. Postoperative satisfaction was achieved by 103 patients. Overall, 383
      patients were able to achieve the preoperative IIEF-EF score. However, only 26.9%
      reported being satisfied. Age and preoperative IIEF-EF score were significantly
      associated with baseline IIEF-EF recovery (all P <= .02). Patients who were able
      to return to baseline IIEF-EF were more likely to be satisfied (P < .001). Time
      elapsed between surgery and achievement of baseline IIEF-EF was significantly
      associated with OS (P < .001). Among patients who were able to achieve the
      baseline IIEF-EF score, a preoperative IIEF-EF of 22-25 and 26-30 was
      significantly associated with postoperative satisfaction (all P < .001).
      CONCLUSION: After BNSRP, reaching the baseline IIEF-EF score is not always
      sufficient to obtain patient satisfaction. Only patients with a preoperative IIEF
      EF >=22 who reached the baseline score after surgery considered themselves
      satisfied. This should be taken into account in preoperative patient counseling.

PMID- 27045264
TI  - Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline
      Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy--Results
      from a Randomized Controlled Trial (REACTT).
AB  - INTRODUCTION AND AIM: The multicenter, randomized, double-blind, double-dummy,
      placebo-controlled REACTT trial suggested that treatment with tadalafil once
      daily (OaD) started early after bilateral nerve-sparing radical prostatectomy
      (nsRP) for prostate cancer may contribute to erectile function (EF)-recovery,
      which was predefined as achieving an International Index of Erectile Function
      (IIEF)-EF score >=22. Here, we report descriptive post-hoc analyses, using the
      more strict definition for EF-recovery of returning back to the pre-surgery IIEF
      EF-level ("back-to-baseline analysis"). METHODS: REACTT included 422 men <68
      years with adenocarcinoma of the prostate and preoperative IIEF-EF >=22 who
      underwent nsRP at 50 centers from 9 European countries and Canada. Patients were
      randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil
      5 mg OaD (n = 139), tadalafil 20 mg on-demand (pro-re-nata, PRN; n = 142), or
      placebo (n = 141), followed by 6-week drug-free washout (DFW) and 3-month open
      label tadalafil OaD treatment (OLT). MAIN OUTCOME MEASURES: Proportion of
      patients returning to their preoperative IIEF-EF category (22-25 or >=26) at the
      end of DBT, DFW, and OLT. RESULTS: Overall, 92.4% of patients had pre-surgery
      (baseline) IIEF-EF scores >=26 (tadalafil OaD 94.2%, PRN 91.6%, placebo 91.5%),
      7.4% had IIEF-EF 22-25. At the end of DBT, 22.3% of patients on tadalafil OaD had
      achieved "back-to-baseline" IIEF-EF, compared with 11.3% on tadalafil PRN and
      7.8% on placebo. Of all 58 patients "back-to-baseline" at the end of DBT, only 1
      PRN-group patient had started from a baseline IIEF-EF <26. The treatment-group
      difference at the end of DBT was not maintained after DFW. After 3 months of OLT
      with tadalafil OaD, the proportion of patients with "back-to-baseline" IIEF-EF
      had almost doubled in all 3 groups. CONCLUSION: Changing the definition for EF
      recovery from IIEF-EF >=22 to the more strict definition of "returning back-to
      baseline IIEF-EF" had no major impact. Tadalafil OaD started early after nsRP
      improved drug-assisted EF, but had no effect on unassisted EF following treatment
      cessation after 9 months.

PMID- 27045265
TI  - Results of SMSNA Survey Regarding Complications Following Intralesional Injection
      Therapy With Collagenase Clostridium Histolyticum for Peyronie's Disease.
AB  - INTRODUCTION: Intralesional injection of collagenase clostridium histolyticum
      (CCH) for Peyronie's disease (PD) can result in serious adverse events such as
      hematoma formation and corporal rupture. AIM: To investigate the prevalence of
      complications from CCH and management trends among CCH prescribers. METHODS: A
      survey was sent to all 693 members of the Sexual Medicine Society of North
      America (SMSNA) with valid email addresses. Responders were asked to participate
      if they were prescribers of CCH. Data regarding prescriber experience with CCH,
      procedural preferences, and rates and management strategies of complications were
      collected. MAIN OUTCOME MEASURE: One hundred SMSNA members completed the survey,
      with 36%, 23%, and 41% of responders having performed <=10, 10 to 20, and >20 CCH
      injections, respectively. RESULTS: Of the responders, 94% reported hematomas in
      <25% of patients, with 63% preferring to observe and 37% treated with a
      combination of observation, application of a compressive dressing, and/or
      drainage of the hematoma. Corporal ruptures were encountered by 34% of physicians
      at a median of 5 days (0.5 to 30 days) from the last CCH injection. Rupture was
      located over the treated plaque in 84% of cases, and surgical intervention was
      the preferred management option by 67% of members. A distal circumcising
      degloving incision was used in 76% of cases, and 62% of responders reported the
      quality of tissue to be worse than would be expected with a non-CCH penile
      fracture. There were no significant differences in erectile function, ability to
      have intercourse, change in penile curvature, and patient satisfaction among
      patients who underwent surveillance vs surgery. One observed patient developed a
      penile abscess. CONCLUSION: A wide variation exists among SMSNA members'
      strategies to prevent and manage complications of CCH. One in 3 prescribers
      reported encountering a corporal rupture during CCH therapy, and it is currently
      undetermined if there is a benefit of surgery vs conservative management.

PMID- 27045266
TI  - Doppler Duplex Ultrasonography of the Penis.

PMID- 27045267
TI  - Erratum.

PMID- 27045268
TI  - Erratum.

PMID- 27045269
TI  - Bone Canopies in Pediatric Renal Osteodystrophy.
AB  - Pediatric renal osteodystrophy (ROD) is characterized by changes in bone
      turnover, mineralization, and volume that are brought about by alterations in
      bone resorption and formation. The resorptive and formative surfaces on the
      cancellous bone are separated from the marrow cavity by canopies consisting of a
      layer of flat osteoblastic cells. These canopies have been suggested to play a
      key role in the recruitment of osteoprogenitors during the process of bone
      remodeling. This study was performed to address the characteristics of the
      canopies above bone formation and resorption sites and their association with
      biochemical and bone histomorphometric parameters in 106 pediatric chronic kidney
      disease (CKD) patients (stage 2-5) across the spectrum of ROD. Canopies in CKD
      patients often appeared as thickened multilayered canopies, similar to previous
      reports in patients with primary hyperparathyroidism. This finding contrasts with
      the thin appearance reported in healthy individuals with normal kidney function.
      Furthermore, canopies in pediatric CKD patients showed immunoreactivity to the
      PTH receptor (PTHR1) as well as to the receptor activator of nuclear factor kappa
      B ligand (RANKL). The number of surfaces with visible canopy coverage was
      associated with plasma parathyroid hormone (PTH) levels, bone formation rate, and
      the extent of remodeling surfaces. Collectively, these data support the
      conclusion that canopies respond to the elevated PTH levels in CKD and that they
      possess the molecular machinery necessary to respond to PTH signaling. 

PMID- 27045270
TI  - Structure of Post-Transplant Care in a Single Transplant Center.
AB  - BACKGROUND: The number of transplant surgeries across the globe has markedly
      increased in recent decades and is associated with improvement in outcomes.
      Factors that could improve the organization of post-transplant care are sought.
      The aim of our study was to evaluate the changes in post-transplant care in the
      largest Polish transplant center from 2010 to 2014. MATERIAL AND METHODS:
      Analysis was performed in all transplant recipients followed up at our center.
      The following factors were evaluated: changes in patient inflow and outflow,
      changes in the number of ambulatory visits, causes of loss to follow-up of the
      patients, and changes in National Health Fund financing. All factors were
      measured in 5-year period from 2010 to 2014. RESULTS: Stable year-to-year patient
      inflow increased by 31% in the total number of patients under follow-up within 5
      years. In the same time, the total NHF spending increased by 32%, but spending
      per patient increased by only 11%. As a consequence, after the initial growth in
      the years 2010-2012, the number of ambulatory visits per patient per year tended
      to decline. CONCLUSIONS: Our study revealed that the real challenge in long-term
      post-transplant care is the increasing number of patients and the increasing
      length of their follow-up. Potential risks related to financial expenditure
      discrepancy between short-term and long-term transplantation procedures were also
      found.

PMID- 27045271
TI  - Predictors of long-term care placement in persons with dementia: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: The main objective of this study was to summarize the effects of
      various individual, caregiver, and system-related factors on the risk of long
      term care (LTC) placement for persons with dementia. METHODS: We searched
      electronic databases for longitudinal studies reporting on predictors of LTC
      placement for persons with dementia residing in the community or supportive care
      settings. We performed meta-analyses with hazard ratios (HRs) of various
      predictors using random effects models and stratified the HRs with several study
      variables. Data on predictors not included in the meta-analyses were summarized
      descriptively. RESULTS: Full-text reviews of 360 papers were performed with data
      from 37 papers used to calculate pooled HRs for LTC placement of select person
      with dementia (age, sex, race, marital status, type of dementia, living
      arrangement, and relationship to caregiver) and caregiver (age, sex, and
      depressive symptoms) characteristics. White race [HR = 1.67, 95% confidence
      intervals (CI): 1.41-1.99], greater dementia severity (HR = 1.05, 95% CI: 1.03
      1.06), and older age (HR = 1.02, 95% CI: 1.01-1.03) increased the risk of LTC
      placement. Married persons with dementia (HR = 0.38, 95% CI: 0.16-0.86) and
      living with their caregiver (HR = 0.72, 95% CI: 0.56-0.92) had a lower risk.
      Behavioral and psychological symptoms of dementia, the degree of functional
      impairment, and caregiver burden had a consistent effect on the risk of LTC
      placement in our descriptive review. CONCLUSION: We quantified the predictive
      effect of several risk factors for LTC placement. These estimates could be used
      to more precisely categorize the risk of institutionalization and potentially
      link those at higher risk to appropriate services. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27045272
TI  - Ultrasound-promoted two-step synthesis of 3-arylselenylindoles and 3
      arylthioindoles as novel combretastatin A-4 analogues.
AB  - A series of 3-(3'-hydroxy-4'-methoxyphenyl)selenyl-5,6,7-trimethoxy-1H-indoles
      and 3-(3'-hydroxy-4'-methoxyphenyl)thio-5,6,7-trimethoxy-1H-indoles were obtained
      as a new class of combretastatin A-4 (CA-4) analogues via a convenient ultrasound
      (US)-assisted two-step process involving 3-selenenylation/sulfenylation followed
      by O-deallylation. With the assistance of US irradiation, both the reaction rates
      and yields of selenenylation, sulfenylation and O-deallylation could be
      significantly improved. A comparison of the reaction rates of O-deallylation and
      ester reduction demonstrated that O-deallylation was more sensitive to US
      irradiation. Finally, these products were evaluated for their antiproliferative
      activities, and most of them showed moderate to potent activities against three
      human cancer cell lines in vitro. 

PMID- 27045273
TI  - Risk factors for postpartum depression in women living with HIV attending
      prevention of mother-to-child transmission clinic at Kenyatta National Hospital,
      Nairobi.
AB  - Mothers with HIV are at high risk of a range of psychosocial issues that may
      impact HIV disease progression for themselves and their children. Stigma has also
      become a substantial barrier to accessing HIV/AIDS care and prevention services.
      The study objective was to determine the prevalence and severity of postpartum
      depression (PPD) among women living with HIV and to further understand the impact
      of stigma and other psychosocial factors in 123 women living with HIV attending
      prevention of mother-to-child transmission (PMTCT) clinic at Kenyatta National
      Hospital located in Nairobi, Kenya. We used the Edinburgh Postnatal Depression
      Scale and HIV/AIDS Stigma Instrument - PLWHA (HASI - P). Forty-eight percent (N =
      59) of women screened positive for elevated depressive symptoms. Eleven (9%) of
      the participants reported high levels of stigma. Multivariate analyses showed
      that lower education (OR = 0.14, 95% CI [0.04-0.46], p = .001) and lack of family
      support (OR = 2.49, 95% CI [1.14-5.42], p = .02) were associated with the
      presence of elevated depressive symptoms. The presence of stigma implied more
      than ninefold risk of development of PPD (OR = 9.44, 95% CI [1.132-78.79], p =
      .04). Stigma was positively correlated with an increase in PPD. PMTCT is an ideal
      context to reach out to women to address mental health problems especially
      depression screening and offering psychosocial treatments bolstering quality of
      life of the mother-baby dyad.

PMID- 27045274
TI  - Does medical therapy influence the size of the syrinx in dogs with Chiari-like
      malformation/syringohydromyelia complex?

PMID- 27045275
TI  - Preschoolers' psychophysiological responses to mood induction tasks moderate the
      intergenerational transmission of internalizing problems.
AB  - To identify factors that can both exacerbate risk for, and protect against,
      internalizing problems during early childhood, the present study examined whether
      children's respiratory sinus arrhythmia (RSA) suppression in response to
      emotionally-laden film clips would moderate the association between maternal and
      child anxious/depressive symptoms in a cross-sectional sample of 108 mothers (M
      age=30.68years, SD=6.06) and their preschool-age children (M age=3.50years,
      SD=0.52, 61.30% male). Results indicated that RSA suppression in response to the
      fear clip moderated the positive association between maternal and child
      anxious/depressive symptoms, such that higher suppression served a protective
      stabilizing function while lower suppression exacerbated children's risk for
      internalizing symptoms in the context of higher maternal symptoms. Moderation
      findings involving RSA suppression in response to a happiness-inducing clip were
      consistent with biological sensitivity to context; the association between
      maternal and child symptoms was strongest for children higher in suppression.

PMID- 27045276
TI  - Calculation of the sun protection factor of sunscreens with different vehicles
      using measured film thickness distribution - Comparison with the SPF in vitro.
AB  - The sun protection factor (SPF) depends on UV filter composition, and amount and
      type of vehicle of the applied sunscreen. In an earlier work, we showed that the
      vehicle affected the average thickness of sunscreen film that is formed upon
      application to a skin substrate and that film thickness correlated significantly
      with SPF in vitro. In the present study, we quantitatively assess the role for
      sunscreen efficacy of the complete film thickness frequency distribution of
      sunscreen measured with an oil-in-water cream, an oil-in-water spray, a gel, a
      water-in-oil, and an alcoholic spray formulation. A computational method is
      employed to determine SPF in silico from calculated UV transmittance based on
      experimental film thickness and thickness distribution, and concentration and
      spectral properties of the UV filters. The investigated formulations exhibited
      different SPFs in vitro and different film thickness distributions especially in
      the small thickness range. We found a very good agreement between SPF in silico
      and SPF in vitro for all sunscreens. This result establishes the relationship
      between sun protection and the film thickness distribution actually formed by the
      applied sunscreen and demonstrates that variation in SPF between formulations is
      primarily due to their film forming properties. It also opens the possibility to
      integrate the influence of vehicle into tools for in silico prediction of the
      performance of sunscreen formulations. For this, the use of the Gamma
      distribution was found to be appropriate for describing film thickness
      distribution. 

PMID- 27045277
TI  - Optimization of process parameters for the rapid biosynthesis of hematite
      nanoparticles.
AB  - Hematite (alpha-Fe2O3) nanoparticles are widely used in various applications
      including gas sensors, pigments owing to its low cost, environmental
      friendliness, non-toxicity and high resistance to corrosion. These nanoparticles
      were generally synthesized by different chemical methods. In the present study,
      nanoparticles were synthesized rapidly without heat treatment by biosynthesis
      approach using culture supernatant of Bacillus cereus SVK1. The physiochemical
      parameters for rapid synthesis were optimized by using UV-visible spectroscopy.
      The time taken for hematite nanoparticle synthesis was found to increase with the
      increasing concentration of the precursor. This might be due to the inadequate
      proportion of quantity of biomolecules present in the culture supernatant to the
      precursor which led to delayed bioreduction. Greater quantities of culture
      supernatant with respect to precursor lead to rapid synthesis of hematite
      nanoparticles. The nucleation of the hematite nucleus happens more easily when
      the solution pH was less than 10. The optimum parameters identified for the rapid
      biosynthesis of hematite nanoparticles were pH9, 37 degrees C (temperature) and
      1mM ferric chloride as precursor. The particles were well crystallized hexagonal
      structured hematite nanoparticles and are predominantly (110)-oriented. The
      synthesized nanoparticles were found to contain predominantly iron (73.47%) and
      oxygen (22.58%) as evidenced by Energy Dispersive X-ray analysis. Hematite
      nanoparticles of 15-40nm diameters were biosynthesized in 48h under optimized
      conditions, compared to 21days before optimization. 

PMID- 27045278
TI  - Protein reactivity with singlet oxygen: Influence of the solvent exposure of the
      reactive amino acid residues.
AB  - The singlet oxygen quenching rate constants were measured for three model
      proteins, bovine serum albumin, beta-lactoglobulin and lysozyme. The results were
      analyzed by comparing them with the corresponding singlet oxygen quenching rate
      constants for a series of tripeptides with the basic formula GlyAAGly where the
      central amino acid (AA) was the oxidizable amino acid, tryptophan, tyrosine,
      methionine and histidine. It was found that the reaction rate constant in
      proteins can be satisfactorily modelled by the sum of the individual
      contributions of the oxidizable AA residues corrected for the solvent accessible
      surface area (SASA) effects. The best results were obtained when the SASA of the
      AA residues were determined by averaging over molecular dynamics simulated
      trajectories of the proteins. The limits of this geometrical correction of the AA
      residue reactivity are also discussed. 

PMID- 27045279
TI  - Cadmium oxide nanoparticles grown in situ on reduced graphene oxide for enhanced
      photocatalytic degradation of methylene blue dye under ultraviolet irradiation.
AB  - Cadmium oxide (CdO) nanoparticles (NPs), reduced graphene oxide (rGO) and rGO-CdO
      nanocomposites have been synthesized using one step hydrothermal method. The
      structural and optical properties of CdO NPs, rGO, and rGO-CdO nanocomposites
      were investigated by X-ray diffraction (XRD), energy dispersive X-ray (EDX), high
      resolution transmission electron microscopy (HR-TEM), Raman spectroscopy (RS),
      ultraviolet-visible spectroscopy (UV-Vis.) and photoluminescence (PL)
      spectroscopy techniques. The rGO has a sharp 2D peak compared to GO. The sharp
      nature of 2D band may be due to the larger contribution from single layer sheet.
      The photocatalytic activity of the synthesized samples has been investigated
      under UV irradiation. The results of photocatalytic measurements revealed that
      ~80% of MB dye is degraded by adding the rGO-CdO nanocomposites as photocatalysts
      into the dye solution. The decrease in the intensity of emission peaks indicates
      that the photogenerated charge carriers have been transferred from CdO NPs to rGO
      sheets, which causes to increase the density of O2(-) and OH radicals in the dye
      solution. The CdO nanoparticles gown on the rGO sheets showed enhanced
      ferromagnetism (FM) at room temperature, which may be attributed to the short
      range magnetic interaction of magnetic moments of CdO NPs and spin units present
      on the rGO sheets. 

PMID- 27045280
TI  - The effect of laser and botulinum toxin in the treatment of myofascial pain and
      mouth opening: A randomized clinical trial.
AB  - This study conducted a randomized clinical trial in 15 patients, who sought care
      at the Dental Clinic of the University of Passo Fundo, in order to compare the
      use of low-level laser and botulinum toxin in the treatment of myofascial pain
      and whether they alter the mouth opening of patients with temporomandibular
      disorder. The patients were divided into two groups: the Laser group received low
      level GaAlAs laser, 100mW of power at a wavelength of 830nm in continuous light
      emission; and the Toxin group received 30U of botulinum toxin type A (BTX-A) in
      the first session, and 15U after fifteen days. The assessments were performed by
      measuring pain with Visual Analogue Scale (VAS), and mouth opening with a digital
      caliper. Data were submitted to Student's t test at 5% significance level.
      Regarding pain symptoms, the results indicate that groups treated with laser and
      toxin registered 7U in VAS, at day 5 the scores were 4.75 and 4.86U,
      respectively. The laser worked faster (day 12) at 2.75U, and the group treated
      with BTX-A registered 2.86U at day 30. Both therapies investigated were effective
      in reducing pain, but the effect of low-level laser was faster than the use of
      BTX-A. Both treatments showed no statistically significant improvement in mouth
      opening. 

PMID- 27045281
TI  - Perceptual dehumanization of faces is activated by norm violations and
      facilitates norm enforcement.
AB  - This article uses methods drawn from perceptual psychology to answer a basic
      social psychological question: Do people process the faces of norm violators
      differently from those of others--and, if so, what is the functional
      significance? Seven studies suggest that people process these faces different and
      the differential processing makes it easier to punish norm violators. Studies 1
      and 2 use a recognition-recall paradigm that manipulated facial-inversion and
      spatial frequency to show that people rely upon face-typical processing less when
      they perceive norm violators' faces. Study 3 uses a facial composite task to
      demonstrate that the effect is actor dependent, not action dependent, and to
      suggest that configural processing is the mechanism of perceptual change. Studies
      4 and 5 use offset faces to show that configural processing is only attenuated
      when they belong to perpetrators who are culpable. Studies 6 and 7 show that
      people find it easier to punish inverted faces and harder to punish faces
      displayed in low spatial frequency. Taken together, these data suggest a
      bidirectional flow of causality between lower-order perceptual and higher-order
      cognitive processes in norm enforcement.

PMID- 27045282
TI  - When asking the question changes the ultimate answer: Metamemory judgments change
      memory.
AB  - Self-report measurements are ubiquitous in psychology, but they carry the
      potential of altering processes they are meant to measure. We assessed whether a
      common metamemory measure, judgments of learning, can change the ongoing process
      of memorizing and subsequent memory performance. Judgments of learning are a form
      of metamemory monitoring described as conscious reflection on one's own memory
      performance or encoding activities for the purpose of exerting strategic control
      over one's study and retrieval activities (T. O. Nelson & Narens, 1990). Much of
      the work examining the conscious monitoring of encoding relies heavily on a
      paradigm in which participants are asked to estimate the probability that they
      will recall a given item in a judgment of learning. In 5 experiments, we find
      effects of measuring judgments of learning on how people allocate their study
      time to difficult versus easy items, and on what they will recall. These results
      suggest that judgments of learning are partially constructed in response to the
      measurement question. The tendency of judgments of learning to alter performance
      places them in the company of other reactive verbal reporting methods, counseling
      researchers to consider incorporating control groups, creating alternative
      scales, and exploring other verbal reporting methods. Less directive methods of
      accessing participants' metacognition and other judgments should be considered as
      an alternative to response scales. 

PMID- 27045283
TI  - Corrigendum to "DRD2/ANKK1 TaqI A genotype moderates the relationship between
      alexithymia and the relative value of alcohol among male college binge drinkers"
      [Pharmacol. Biochem. Behav. 102 (2012) 471-476].

PMID- 27045284
TI  - Host-guest interaction enhanced aggregation-induced emission and its application
      in cell imaging.
AB  - A host-guest inclusion complex based on a monofunctionalized pillar[5]arene and a
      tetraphenylethene derivative was prepared, resulting in an enhanced emission from
      the tetraphenylethene-based guest, which was applied in cell imaging. 

PMID- 27045285
TI  - At-home vs In-office Bleaching: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis were performed to evaluate the
      risk and intensity of tooth sensitivity during in-office and at-home bleaching in
      adult patients. The efficacy of dental bleaching was also evaluated. METHODS: A
      comprehensive search was performed in the MEDLINE via PubMed, Scopus, Web of
      Science, Latin American and Caribbean Health Sciences Literature database,
      Brazilian Library in Dentistry, Cochrane Library, and System for Information on
      Grey Literature in Europe without restrictions. The annual conference of the
      International Association for Dental Research abstracts (1990-2014) and
      unpublished and ongoing trials registry were also searched. Dissertations and
      theses were searched using the ProQuest Dissertations and Periodicos Capes Theses
      databases. Only randomized clinical trials that compared the prevalence or
      intensity of tooth sensitivity during in-office and at-home bleaching in adult
      patients were included and studies that evaluated the efficacy of these dental
      bleaching techniques, in terms of shade guide units (DeltaSGU) and in terms of
      color difference measured with a spectrophotometer (DeltaE*). RESULTS: After the
      removal of duplicates, 1139 articles were identified. After title and abstract
      screening, 29 studies remained. Fifteen studies were further excluded, whereas 12
      studies remained for qualitative analyses and 8 for the meta-analysis of the
      primary and secondary outcomes. No significant difference in the risk/intensity
      of tooth sensitivity or in bleaching efficacy was observed in the present study.
      CONCLUSION: In an overall comparison of at-home and in-office bleaching, no
      differences were detected, either regarding risk/intensity of tooth sensitivity
      or the effectiveness of the bleaching treatment. This comparison, however, does
      not take into consideration variations in the protocols (daily usage time, number
      of bleaching sessions, and product concentration) of the bleaching techniques in
      the studies included.

PMID- 27045286
TI  - Evaluation of Radiopacity of Bulk-fill Flowable Composites Using Digital
      Radiography.
AB  - New flowable composites that may be bulk-filled in layers up to 4 mm are
      indicated as a base beneath posterior composite restorations. Sufficient
      radiopacity is one of the several important requirements such materials should
      meet. The aim of this study was to evaluate the radiopacity of bulk-fill flowable
      composites and to provide a comparison with conventional flowable composites
      using digital imaging. Ten standard specimens (5 mm in diameter, 1 mm in
      thickness) were prepared from each of four different bulk-fill flowable
      composites and nine different conventional flowable composites. Radiographs of
      the specimens were taken together with 1-mm-thick tooth slices and an aluminum
      step wedge using a digital imaging system. For the radiographic exposures, a
      storage phosphor plate and a dental x-ray unit at 70 kVp and 8 mA were used. The
      object-to-focus distance was 30 cm, and the exposure time was 0.2 seconds. The
      gray values of the materials were measured using the histogram function of the
      software available with the system, and radiopacity was calculated as the
      equivalent thickness of aluminum. The data were analyzed statistically (p<0.05).
      All of the tested bulk-fill flowable composites showed significantly higher
      radiopacity values in comparison with those of enamel, dentin, and most of the
      conventional flowable composites (p<0.05). Venus Bulk Fill (Heraeus Kulzer)
      provided the highest radiopacity value, whereas Arabesk Flow (Voco) showed the
      lowest. The order of the radiopacity values for the bulk-fill flowable composites
      was as follows: Venus Bulk Fill (Heraeus Kulzer) >= X-tra Base (Voco) > SDR
      (Dentsply DeTrey) >= Filtek Bulk Fill (3M ESPE). To conclude, the bulk-fill
      flowable restorative materials, which were tested in this study using digital
      radiography, met the minimum standard of radiopacity specified by the
      International Standards Organization. 

PMID- 27045287
TI  - Degree of Conversion of Self-etch Adhesives: In Situ Micro-Raman Analysis.
AB  - PURPOSE: Degree of conversion (DC) affects the physicochemical properties of
      dental adhesives. The aim of this study was to measure the DC within the hybrid
      layer of four one-step self-etch adhesives using Raman microspectroscopy. The
      hypothesis tested was that there was no difference among the tested adhesives.
      METHODS AND MATERIALS: The selected one-step self-etch adhesives (Clearfil S3
      Bond Plus, I-BOND, G-BOND, and Adper Easy Bond) were applied on human dentin
      disks and polymerized in accordance with the manufacturers' instructions.
      Specimens were transversally cut to expose the bonded interfaces to the micro
      Raman beam, and Raman spectra were collected along the dentin/adhesive interface.
      Measurements were performed at 1-MUm intervals. The relative intensities of bands
      associated with the C=C bond (at 1640 cm-1) and an internal stable peak (1610 cm
      1) were determined to calculate the degree of conversion within the hybrid layer.
      Data were statistically analyzed with Kolmogorov-Smirnov and Bartlett tests and
      Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: The DC ranked as follows: G
      BOND (93%+/-6%) >= Adper Easy Bond (92%+/-6%) >= I-BOND (89%+/-7%) > Clearfil S3
      Bond Plus (80%+/-14%) (p<0.05). CONCLUSIONS: Based on the results of this study,
      all of the tested self-etch adhesives showed a clinically acceptable DC that was
      material dependent.

PMID- 27045288
TI  - Can Children Reduce Delayed Hospital Arrival for Ischemic Stroke?: A Systematic
      Review of School-Based Stroke Education.
AB  - BACKGROUND: Delayed hospital arrival after onset of ischemic stroke reduces the
      number of patients eligible for tissue plasminogen activator, which must be given
      soon after stroke onset. There are conflicting results about the impact of mass
      media stroke education on timing of hospital arrival and tissue plasminogen
      activator administration rates. School-based programs are a new way to
      communicate stroke information. METHODS: A search of MEDLINE, CINAHL, PsycINFO,
      and ERIC databases from 1995 to 2014 identified school-based stroke education
      interventions. Twelve studies involving 3,312 children and 612 parents met
      criteria for review. RESULTS: School-based stroke education interventions were
      effective to improve knowledge of stroke symptoms among children in kindergarten
      through junior high. Improvement for stroke risk factors was less robust.
      Interventions were effective regardless of format, length, or who delivered the
      information. Despite low parental response rates in some studies, there was
      evidence that children transmitted stroke information to parents. CONCLUSIONS:
      School-based stroke education programs appear effective to improve knowledge of
      stroke symptoms. Research is needed to determine if children who participate are
      able to recognize stroke and respond appropriately by calling 911 in the real
      world. More study is needed about transfer of stroke knowledge from child to
      parent. Strategies to improve parent participation are needed.

PMID- 27045289
TI  - Pain Assessment Scale for Patients With Disorders of Consciousness: A Preliminary
      Validation Study.
AB  - BACKGROUND: Patients with acquired brain injury undergoing rehabilitation are
      often unable to verbalize pain because of disorders of consciousness. Hence,
      observational pain assessment instruments are warranted for these patients. AIM:
      The aim of this study was to study interrater agreement and sensitivity to change
      over time of an assessment scale developed for the evaluation of pain in severely
      brain-injured patients with disorders of consciousness. METHODS: We developed a
      pain assessment scale based on scientific literature and clinical experience with
      severely brain-injured patients. It consists of four domains:
      physiological/autonomic, body language, verbal communication, and behavior. The
      domains consist of 27 items. Interrater reliability was tested through three
      experienced nurses who rated 26 patients with acquired brain injury. The patients
      were rated in two different situations: before and after repositioning in bed and
      before and after administration of analgesics. We used Cohen's kappa test for
      interrater reliability. Sensitivity to change was tested by Wilcoxon signed rank
      test. RESULTS: Cohen's kappa for the presence or absence of each item was above
      0.8 for 13 items, between 0.6 and 0.8 for eight items, and less than 0.6 for only
      three items. The sensitivity test showed a significant change from before to
      after repositioning (p = .004). CONCLUSION: It appeared that many of the pain
      assessment scale items held potential for inclusion in a new, more
      comprehensively developed and validated scale for the assessment of pain in
      patients with disorders of consciousness.

PMID- 27045290
TI  - Calcium oxalate crystals increased enolase-1 secretion from renal tubular cells
      that subsequently enhanced crystal and monocyte invasion through renal
      interstitium.
AB  - Calcium oxalate monohydrate (COM) crystals cause kidney stone disease by still
      unclear mechanisms. The present study aimed to characterize changes in secretion
      of proteins from basolateral compartment of renal tubular epithelial cells after
      exposure to COM crystals and then correlated them with the stone pathogenesis.
      Polarized MDCK cells were cultivated in serum-free medium with or without 100
      MUg/ml COM crystals for 20 h. Secreted proteins collected from the lower chamber
      (basolateral compartment) were then resolved in 2-D gels and visualized by Deep
      Purple stain (n = 5 gels/group). Spot matching and intensity analysis revealed
      six protein spots with significantly altered levels in COM-treated samples. These
      proteins were then identified by tandem mass spectrometry (Q-TOF MS/MS),
      including enolase-1, phosphoglycerate mutase-1, actinin, 14-3-3 protein epsilon,
      alpha-tubulin 2, and ubiquitin-activating enzyme E1. The increased enolase-1
      level was confirmed by Western blot analysis. Functional analysis revealed that
      enolase-1 dramatically induced COM crystal invasion through ECM migrating chamber
      in a dose-dependent manner. Moreover, enolase-1 bound onto U937 monocytic cell
      surface markedly enhanced cell migration through the ECM migrating chamber. In
      summary, our data indicated that the increased secretory enolase-1 induced by COM
      crystals played an important role in crystal invasion and inflammatory process in
      renal interstitium. 

PMID- 27045291
TI  - Renal Transplant Recipients Treated with Calcineurin-Inhibitors Lack Circulating
      Immature Transitional CD19+CD24hiCD38hi Regulatory B-Lymphocytes.
AB  - BACKGROUND: CD19+CD24hiCD38hi transitional immature B-lymphocytes have been
      demonstrated to play an important role in regulating the alloimmune response in
      transplant recipients. Here, we analyzed the effect of calcineurin inhibition on
      these peripherally circulating regulatory B-cells (Breg) in renal transplant
      recipients receiving cyclosporine A (CsA) or tacrolimus. METHODS: PBMCs from
      healthy subjects (HS) (n = 16) and renal transplant recipients (n = 46) were
      isolated. Flow cytometry was performed for CD19, CD24, CD38 and IL-10 either
      after isolation or after 72 hours of co-culture in presence of PMA/Ionomycin and
      TLR9-ligand in presence or absence of increasing concentrations of tacrolimus or
      CsA. RESULTS: The amount of CD19+ B-cells among lymphocytes was ~9.1% in HS,
      ~3.6% in CsA (n = 11, p<0.05) and ~6.4% in TAC (n = 35, p<0.05) treated patients.
      Among B-cells, a distinct subset of Breg was found to be 4.7% in HS, 1.4% in
      tacrolimus treated patients and almost blunted in patients receiving CsA.
      Similarily, ~4% of B-cells in HS and even fewer in CsA or tacrolimus treated
      patients produced IL-10 (0.5% and 1.5%, p<0.05) and this was confirmed both in
      non-transplanted CsA-treated healthy subjects and in in vitro co-culture
      experiments. Among 29 patients with <1% of Breg, 9 cases (31%) displayed an
      allograft rejection in contrast to only one case of rejection (6%) among 17
      patients with >1%. CONCLUSION: Calcineurin inhibitors reduce number and IL-10
      production of Bregs in the peripheral circulation of both renal transplant
      recipients and non-transplanted healthy subjects. CNI induced Breg reduction is
      not restricted to a solid organ transplant setting and is not mediated by co
      medication with steroids or MPA. A low proportion of Breg cells is associated
      with an elevated frequency of allograft rejection events.

PMID- 27045292
TI  - Representing Representation: Integration between the Temporal Lobe and the
      Posterior Cingulate Influences the Content and Form of Spontaneous Thought.
AB  - When not engaged in the moment, we often spontaneously represent people, places
      and events that are not present in the environment. Although this capacity has
      been linked to the default mode network (DMN), it remains unclear how
      interactions between the nodes of this network give rise to particular mental
      experiences during spontaneous thought. One hypothesis is that the core of the
      DMN integrates information from medial and lateral temporal lobe memory systems,
      which represent different aspects of knowledge. Individual differences in the
      connectivity between temporal lobe regions and the default mode network core
      would then predict differences in the content and form of people's spontaneous
      thoughts. This study tested this hypothesis by examining the relationship between
      seed-based functional connectivity and the contents of spontaneous thought
      recorded in a laboratory study several days later. Variations in connectivity
      from both medial and lateral temporal lobe regions was associated with different
      patterns of spontaneous thought and these effects converged on an overlapping
      region in the posterior cingulate cortex. We propose that the posterior core of
      the DMN acts as a representational hub that integrates information represented in
      medial and lateral temporal lobe and this process is important in determining the
      content and form of spontaneous thought. 

PMID- 27045293
TI  - The "Buruli Score": Development of a Multivariable Prediction Model for Diagnosis
      of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions,
      Akonolinga, Cameroon.
AB  - BACKGROUND: Access to laboratory diagnosis can be a challenge for individuals
      suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to
      assist clinicians working in resource-limited settings for BU diagnosis.
      METHODODOLOGY/PRINCIPAL FINDINGS: Between 2011 and 2013, individuals presenting
      at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical
      data were collected prospectively. Based on a latent class model using laboratory
      test results (ZN, PCR, culture), patients were categorized into high, or low BU
      likelihood. Variables associated with a high BU likelihood in a multivariate
      logistic model were included in the Buruli score. Score cut-offs were chosen
      based on calculated predictive values. Of 325 patients with an ulcerative lesion,
      51 (15.7%) had a high BU likelihood. The variables identified for the Buruli
      score were: characteristic smell (+3 points), yellow color (+2), female gender
      (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at
      rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40
      years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82-0.89),
      indicating good discrimination between infected and non-infected individuals. The
      cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0
      98.6). The treatment threshold was set at a cut-off >=4 (PPV 69.0%; 95%CI 49.2
      84.7). Patients with intermediate BU probability needed to be tested by PCR.
      CONCLUSIONS/SIGNIFICANCE: We developed a decisional algorithm based on a clinical
      score assessing BU probability. The Buruli score still requires further
      validation before it can be recommended for wide use.

PMID- 27045294
TI  - Case of Large Cecoureterocele with Contralateral Renal Rupture in Neonate.
AB  - A cecoureterocele is a rare form of ectopic ureterocele that the orifice of the
      affected ureter is within the bladder, but the cavity of the ureterocele extends
      beyond the bladder neck into the urethra. We present a case of a newborn boy with
      a large cecoureterocele with contralateral renal rupture. He required an
      emergency transurethral incision of the ureterocele for the treatment of acute
      renal failure and respiratory disorder. 

PMID- 27045295
TI  - Learning Effective Connectivity Network Structure from fMRI Data Based on
      Artificial Immune Algorithm.
AB  - Many approaches have been designed to extract brain effective connectivity from
      functional magnetic resonance imaging (fMRI) data. However, few of them can
      effectively identify the connectivity network structure due to different defects.
      In this paper, a new algorithm is developed to infer the effective connectivity
      between different brain regions by combining artificial immune algorithm (AIA)
      with the Bayes net method, named as AIAEC. In the proposed algorithm, a brain
      effective connectivity network is mapped onto an antibody, and four immune
      operators are employed to perform the optimization process of antibodies,
      including clonal selection operator, crossover operator, mutation operator and
      suppression operator, and finally gets an antibody with the highest K2 score as
      the solution. AIAEC is then tested on Smith's simulated datasets, and the effect
      of the different factors on AIAEC is evaluated, including the node number,
      session length, as well as the other potential confounding factors of the blood
      oxygen level dependent (BOLD) signal. It was revealed that, as contrast to other
      existing methods, AIAEC got the best performance on the majority of the datasets.
      It was also found that AIAEC could attain a relative better solution under the
      influence of many factors, although AIAEC was differently affected by the
      aforementioned factors. AIAEC is thus demonstrated to be an effective method for
      detecting the brain effective connectivity. 

PMID- 27045297
TI  - Molecular Markers of Antimicrobial Resistance in Methicillin-Resistant
      Staphylococcus aureus SCCmec IV Presenting Different Genetic Backgrounds.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) carrying SCCmec type IV has
      emerged in hospitals worldwide. The aim of this study was to evaluate phenotypic
      and molecular characteristics of antimicrobial resistance in MRSA SCCmec IV
      isolates, presenting different genetic backgrounds, isolated from hospitals in
      Rio de Janeiro. The antimicrobial resistance of 128 S. aureus type IV isolates
      from 11 hospitals was characterized by the disk diffusion test and minimum
      inhibitory concentration (MIC) test. Mutations in parC gene, which encodes
      ciprofloxacin resistance, and genes associated with macrolide-lincosamide
      streptogramin B (MLSb) resistance were also investigated. MRSA isolates belonging
      to USA400/ST1 (60 isolates), USA800/ST5 (40), USA1100/ST30 (13), and other 11
      (15) lineages were mainly resistant to erythromycin (68%), ciprofloxacin (56%),
      and clindamycin (50%). The highest antimicrobial resistance rates were found
      among USA400 isolates (p < 0.05). The majority of them (90%) carried only the
      erm(C) gene and mainly presented two mutation types in the parC gene. The msr(A)
      gene was most frequently found among USA800 isolates (p < 0.05). Among MRSA type
      IV isolates from Rio de Janeiro hospitals, multiresistance, including mutations
      in parC gene, was associated to the USA400/ST1, while the msr(A) gene was
      associated with USA800/ST5 isolates, highlighting that these lineages could have
      more potential to persist in a hospital environment.

PMID- 27045296
TI  - A Meta-Assembly of Selection Signatures in Cattle.
AB  - Since domestication, significant genetic improvement has been achieved for many
      traits of commercial importance in cattle, including adaptation, appearance and
      production. In response to such intense selection pressures, the bovine genome
      has undergone changes at the underlying regions of functional genetic variants,
      which are termed "selection signatures". This article reviews 64 recent (2009
      2015) investigations testing genomic diversity for departure from neutrality in
      worldwide cattle populations. In particular, we constructed a meta-assembly of
      16,158 selection signatures for individual breeds and their archetype groups
      (European, African, Zebu and composite) from 56 genome-wide scans representing
      70,743 animals of 90 pure and crossbred cattle breeds. Meta-selection-scores
      (MSS) were computed by combining published results at every given locus, within a
      sliding window span. MSS were adjusted for common samples across studies and were
      weighted for significance thresholds across and within studies. Published
      selection signatures show extensive coverage across the bovine genome, however,
      the meta-assembly provides a consensus profile of 263 genomic regions of which
      141 were unique (113 were breed-specific) and 122 were shared across cattle
      archetypes. The most prominent peaks of MSS represent regions under selection
      across multiple populations and harboured genes of known major effects (coat
      color, polledness and muscle hypertrophy) and genes known to influence polygenic
      traits (stature, adaptation, feed efficiency, immunity, behaviour, reproduction,
      beef and dairy production). As the first meta-assembly of selection signatures,
      it offers novel insights about the hotspots of selective sweeps in the bovine
      genome, and this method could equally be applied to other species. 

PMID- 27045298
TI  - Proud to be a woman: Womanhood, old age, and emotions.
AB  - This article takes its starting point in the discussions regarding intersecting
      discourses of gender and age and the lived experience of older women. The main
      objective is to discuss the experience of womanhood among older women and to
      demonstrate their active role in creating spaces for themselves and their friends
      and affecting each other. The study is based on narrative interviews with female
      members of the University of the Third Age (U3A). The main findings describe
      older women who actively engage with discourses of gender to embark on positive
      constructions of womanhood. They create their own spaces for women's activism
      that are filled with positive emotions mobilized to support each other. This
      article discusses such findings and their relevance to the study of old age and
      gender. As a result, it serves as an invitation to think and feel differently
      about older women and their experience of womanhood. 

PMID- 27045299
TI  - How Clinicians Can Reduce "Bullied Acquiescence".
AB  - Clinicians and patients and their families may disagree about a course of
      treatment, and the ensuing conflict may seem intractable. The parties may request
      mediation, or use mediation-based approaches, to help resolve the conflict. In
      the process of mediation, and at other times, parties in conflict may feel so
      pressured to accept a resolution that they acquiesce unwillingly--and such
      resolutions often unravel. In this article I investigate how "bullied
      acquiescence" might happen, and how to avoid it.

PMID- 27045300
TI  - The Effectiveness of Standardized Patient Simulation in Training Hospital Ethics
      Committees.
AB  - Clinical simulation using standardized patients has become standard in medical
      education--and is now being incorporated into some graduate programs in bioethics
      -for both formative and summative evaluation. In most hospitals, though, clinical
      ethics consultation is done by the ethics committee (or a subset of it). This
      study is the first, to our knowledge, to examine the effectiveness of
      standardized patient simulation in training hospital ethics committees to deal
      with ethically complex and emotionally fraught clinical situations. Following a
      substantial revision of the institution's nonbeneficial treatment policy, ethics
      committee members underwent a simulation to determine whether a specific
      requested treatment should be withheld on the basis of futility. Pre- and post
      intervention surveys showed improvement in all domains, although the small sample
      size limited the power of the study, with only one measure showing a
      statistically significant difference. An interesting incidental finding was that
      one-quarter of committee members voted against a determination of futility, even
      though the case clearly met the definition set forth in the policy. This
      highlights the emotional challenges in implementing an ethically rigorous,
      unanimously accepted policy that ultimately determines the timing and manner of a
      patient's death.

PMID- 27045301
TI  - Clinical Recommendations in Medical Practice: A Proposed Framework to Reduce Bias
      and Improve the Quality of Medical Decisions.
AB  - Patients rely on, benefit from, and are strongly influenced by physicians'
      recommendations. In spite of the centrality and importance of physicians'
      recommendations to clinical care, there is only a scant literature describing the
      conceptual process of forming a clinical recommendation, and no discrete
      professional standards for making individual clinical recommendations. Evidence
      based medicine and shared decision making together are intended to improve
      medical decision making, but there has been limited attention to how a
      recommendation is discretely formulated from either of those processes or how
      patients' preferences ought to be considered and how much weight they should
      hold. Moreover, physicians' bias has been reported to strongly influence how a
      recommendation is derived, thereby undermining the quality of healthcare
      decisions and patients' trust. To demonstrate a potential for improving the
      quality of decisions, this article proposes a conceptual framework for how
      physicians should reach a clinical recommendation and apply the process in
      practice. For preference-sensitive clinical decisions-that is, clinical decisions
      when patients' values and preferences are relevant-the process for reaching a
      recommendation should be transparent to patients and should be based solely on
      the medical evidence and patients' values and preferences. When patients'
      preferences for care do not prioritize health, physicians decide whether their
      recommendation will prioritize a welfare-enhancing versus an autonomy-enhancing
      approach. When there are gaps in understanding how physicians derive their
      clinical recommendations and how to further improve the quality of the decisions,
      the author calls for further empiric research. 

PMID- 27045302
TI  - The Role of Communication and Interpersonal Skills in Clinical Ethics
      Consultation: The Need for a Competency in Advanced Ethics Facilitation.
AB  - Clinical ethics consultants (CECs) often face some of the most difficult
      communication and interpersonal challenges that occur in hospitals, involving
      stressed stakeholders who express, with strong emotions, their preferences and
      concerns in situations of personal crisis and loss. In this article we will give
      examples of how much of the important work that ethics consultants perform in
      addressing clinical ethics conflicts is incompletely conceived and explained in
      the American Society of Bioethics and Humanities Core Competencies for Healthcare
      Ethics Consultation and the clinical ethics literature. The work to which we
      refer is best conceptualized as a specialized type of interviewing, in which the
      emotional barriers of patients and their families or surrogates can be identified
      and addressed in light of relevant ethical obligations and values within the
      context of ethics facilitation. 

PMID- 27045303
TI  - A Case of Attempted Suicide in Huntington's Disease: Ethical and Moral
      Considerations.
AB  - A 62-year-old female with Huntington's disease presented after a suicide attempt.
      Her advance directive stated that she did not want intubation or resuscitation,
      which her family acknowledged and supported. Despite these directives, she was
      resuscitated in the emergency department and continued to state that she would
      attempt suicide again. Her suicidality in the face of a chronic and advancing
      illness, and her prolonged consistency in her desire to take her own life, left
      careproviders wondering how to provide ethical, respectful care to this patient.
      Tension between the ethical principles of autonomy and beneficence is central in
      this case. The patient's narrative demonstrated that her suicide was an
      autonomous decision, free from coercion or disordered thinking from mental
      illness. Beneficence then would seem to necessitate care aligned with the
      patient's desire to end her life, which created ethical uneasiness for her family
      and careproviders. The case highlights several end-of-life ethical considerations
      that have received much recent attention. With ongoing discussions about the
      legalization of aid in dying across the country, caregivers are challenged to
      understand what beneficence means in people with terminal illnesses who want a
      say in their death. This case also highlights the profound moral distress of
      families and careproviders that arises in such ethically challenging scenarios. 

PMID- 27045304
TI  - Story of a Mediation in the Clinical Setting.
AB  - Conflicts in the clinical setting can spiral downward with remarkable speed, as
      parties become ever more incensed and entrenched in their positions. Productive
      conversations seem unlikely at best. Nevertheless, such situations can sometimes
      be turned into collaborative problem solving with equally remarkable speed. For
      this to happen, those providing conflict-resolution services such as mediation
      need to bring, not just a set of skills, but also some key norms: the process
      must be voluntary for all; the mediator must abjure giving advice or taking
      sides, and must honor the privacy of privately offered thoughts. This article
      describes a conflict that had reached the point of a hospital's requesting
      judicial coercion. However, a conflict-resolution process was then initiated
      that, in the end, led to amicable resolution and mended relationships, obviating
      the need for court orders. This article describes that conflict and the
      resolution process in detail, along the way annotating specific strategies that
      are often highly effective. 

PMID- 27045305
TI  - The Case of Ms D: A Family's Request for Posthumous Procurement of Ovaries.
AB  - The MedStar Washington Hospital Center clinical ethics team became involved in a
      case when the family requested the posthumous removal of a patient's ovaries for
      future reproductive use. This case presents a novel question for clinical
      ethicists, since the technology for posthumous female reproduction is still in
      development. In the bioethics literature, the standard position is to refuse to
      comply with such a request, unless there is explicit consent or evidence of
      explicit conversations that demonstrate the deceased would have wanted this
      option pursued. Ms D's case, we suggest, offers an exception to this default
      position; complying with the family's request could have been ethically
      permissible in this case, had it been medically feasible. 

PMID- 27045306
TI  - Analysis: OB/GYN-Genetics.
AB  - Ovarian salvage from a patient with brain death is not available and will not
      preserve viable ova for future reproduction. Previous interest in assisted
      reproductive technology is only the first step in this process, which requires
      careful assessment of maternal risks and potential for recurrent genetic disease.

PMID- 27045307
TI  - Analysis: Fertility Preservation.
AB  - This commentary considers the viability of ovarian tissue cryopreservation (OTC)
      in the case of an adult who qualified for brain death. Although there has been
      some success with OTC in achieving pregnancy when the tissue is reimplanted in
      the original donor, attempting OTC in the case under discussion would have not
      been medically feasible. 

PMID- 27045308
TI  - Analysis: A Legal Perspective.
AB  - This commentary summarizes the uncertain state of the law regarding consent for
      posthumous gamete retrieval. The emergence of a legal framework will be aided by
      the kind of ethical analysis prompted by this family's request for removal and
      preservation of a deceased patient's ovaries. 

PMID- 27045309
TI  - Ethical Considerations of Whole-Eye Transplantation.
AB  - Whole eye transplantation (WET) remains experimental. Long presumed impossible,
      recent scientific advances regarding WET suggest that it may become a clinical
      reality. However, the ethical implications of WET as an experimental therapeutic
      strategy remain largely unexplored. This article evaluates the ethical
      considerations surrounding WET as an emerging experimental treatment for vision
      loss. A thorough review of published literature pertaining to WET was performed;
      ethical issues were identified during review of the articles. 

PMID- 27045310
TI  - Let's Not Forget about Clinical Ethics Committees!
AB  - The aim of this article is to highlight the under-recognized merits of clinical
      ethics committees (CECs), to help ensure that the development of roles for
      clinical ethics consultants do not unwittingly compromise the valuable
      contributions that CECs can continue to provide. I argue that CECs can offer
      distinctive contributions to the clinical ethics consultation process that can
      complement and enrich the input provided by a clinical ethics consultant. These
      distinctions and complementarities should be further examined and developed. This
      will help to optimize the synergistic contributions that CECs and clinical ethics
      consultants can make to promote the ethical treatment of patients and their
      families. 

PMID- 27045311
TI  - Moving Clinical Deliberations on Administrative Discharge in Drug Addiction
      Treatment Beyond Moral Rhetoric to Empirical Ethics.
AB  - Patients' admission to modern substance use disorder treatment comes with the
      attendant risk of being discharged from treatment-a widespread practice. This
      article describes the three mainstream theories of addiction that operate as a
      reference point for clinicians in reasoning about a decision to discharge a
      patient from treatment. The extant literature is reviewed to highlight the
      pathways that patients follow after administrative discharge. Little scientific
      research has been done to investigate claims and hypotheses about the therapeutic
      function of AD, which points to the need for empirical ethics to inform clinical
      addictions practice. 

PMID- 27045312
TI  - Legal Briefing: Mandated Reporters and Compulsory Reporting Duties.
AB  - This issue's "Legal Briefing" column, one product of a Greenwall Foundation
      grant, reviews recent developments concerning compulsory reporting duties. Most
      licensed clinicians in the United States are "mandated reporters." When these
      clinicians discover certain threats to the safety of patients or the public, they
      are legally required to report that information to specified government
      officials. Over the past year, several states have legislatively expanded the
      scope of these reporting duties. In other states, new court cases illustrate the
      vigorous enforcement of already existing duties. I have organized all these legal
      developments into the following eight categories: 1. Overview of Mandatory
      Reporting Duties 2. Controversy over the Benefits of Mandatory Reporting 3. New
      and Expanded Duties to Report 4. Criminal Penalties for Failing to Report 5.
      Civil Liability for Failing to Report 6. Disciplinary Penalties for Failing to
      Report 7. Legal Immunity for Good-Faith Reporting 8. Protection against
      Employers' Retaliation. 

PMID- 27045313
TI  - Revealing a new activity of the human Dicer DUF283 domain in vitro.
AB  - The ribonuclease Dicer is a multidomain enzyme that plays a fundamental role in
      the biogenesis of small regulatory RNAs (srRNAs), which control gene expression
      by targeting complementary transcripts and inducing their cleavage or repressing
      their translation. Recent studies of Dicer's domains have permitted to propose
      their roles in srRNA biogenesis. For all of Dicer's domains except one, called
      DUF283 (domain of unknown function), their involvement in RNA substrate
      recognition, binding or cleavage has been postulated. For DUF283, the interaction
      with Dicer's protein partners has been the only function suggested thus far. In
      this report, we demonstrate that the isolated DUF283 domain from human Dicer is
      capable of binding single-stranded nucleic acids in vitro. We also show that
      DUF283 can act as a nucleic acid annealer that accelerates base-pairing between
      complementary RNA/DNA molecules in vitro. We further demonstrate an annealing
      activity of full length human Dicer. The overall results suggest that Dicer,
      presumably through its DUF283 domain, might facilitate hybridization between
      short RNAs and their targets. The presented findings reveal the complex nature of
      Dicer, whose functions may extend beyond the biogenesis of srRNAs. 

PMID- 27045314
TI  - A Map-Based Service Supporting Different Types of Geographic Knowledge for the
      Public.
AB  - The internet enables the rapid and easy creation, storage, and transfer of
      knowledge; however, services that transfer geographic knowledge and facilitate
      the public understanding of geographic knowledge are still underdeveloped to
      date. Existing online maps (or atlases) can support limited types of geographic
      knowledge. In this study, we propose a framework for map-based services to
      represent and transfer different types of geographic knowledge to the public. A
      map-based service provides tools to ensure the effective transfer of geographic
      knowledge. We discuss the types of geographic knowledge that should be
      represented and transferred to the public, and we propose guidelines and a method
      to represent various types of knowledge through a map-based service. To
      facilitate the effective transfer of geographic knowledge, tools such as
      auxiliary background knowledge and auxiliary map-reading tools are provided
      through interactions with maps. An experiment conducted to illustrate our idea
      and to evaluate the usefulness of the map-based service is described; the results
      demonstrate that the map-based service is useful for transferring different types
      of geographic knowledge. 

PMID- 27045315
TI  - First Report of Human Fascioliasis in an Endemic Region of Bovine Fascioliasis in
      Caldas-Colombia.
AB  - Fascioliasis causes significant economic losses to the cattle industry and is
      considered a reemerging zoonosis. In Caldas-Colombia, an increase of bovine
      fascioliasis was detected at the Manizales Municipal Slaughterhouse, which is a
      potential risk to public health. The ecoepidemiology of human fascioliasis was
      analyzed in a region of bovine fascioliasis in Caldas-Colombia. The risk factors
      were studied. Samples were taken from 111 people who were directly related to the
      bovine milk production process. The immunoglobulin G frequency of Fasciola
      hepatica was determined in serum. A seriate stool test and a molecular analysis
      were conducted on those with positive results to look for parasite eggs and DNA,
      respectively. 6.3% of the samples were positive for the presence of antibodies;
      none was positive for the presence of eggs, while two samples showed a weak
      amplification band of the 124-bp DNA fragment of F. hepatica. Fifty-seven percent
      of the positive samples came from places located at 2026 meters above sea level
      (masl); 71% of people testing positive had been recently dewormed. Also, 86% had
      been in contact with cattle and handled grass and excrement. They eat salads and
      drink untreated water from the springs or ravines of the area. An outbreak of
      human fascioliasis was detected in Caldas, associated with risk factors for the
      disease. Clinical trials to confirm the presence of the parasite and implement
      public health control measures are required.

PMID- 27045316
TI  - Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin
      elasticity via suppression of overexpression of MMPs in hairless mice.
AB  - This study reports the effects of oral Aloe vera gel powder (AVGP) containing
      Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B
      (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets
      containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated
      with AVGP showed significant prevention of the UVB-induced decrease in skin
      elasticity. To investigate the mechanism underlying this suppression of skin
      elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, 
      9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions.
      Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and
      gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration
      prevented UVB-induced decreasing in skin HA content and Has2 expression and
      attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2
      expression. These results suggested that AVGP has the ability to prevent the skin
      photoaging. 

PMID- 27045317
TI  - Differential clonal evolution in oesophageal cancers in response to neo-adjuvant
      chemotherapy.
AB  - How chemotherapy affects carcinoma genomes is largely unknown. Here we report
      whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled
      before and after neo-adjuvant chemotherapy. Most, but not all, good responders
      pass through genetic bottlenecks, a feature associated with higher mutation
      burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow
      by the time of surgical resection, suggesting a missed therapeutic opportunity.
      Cancers often show major changes in driver mutation presence or frequency after
      treatment, owing to outgrowth persistence or loss of sub-clones, copy number
      changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy
      mutation spectrum shifts are also common, particularly C>A and TT>CT changes in
      good responders or bottleneckers. Post-treatment samples may also acquire
      mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that
      are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can
      rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring
      molecular changes during treatment may be clinically useful. 

PMID- 27045318
TI  - Substantially higher prevalence of postoperative peri-prosthetic fractures in
      octogenarians with hip fractures operated with a cemented, polished tapered stem
      rather than an anatomic stem.
AB  - Background and purpose - Recent studies have demonstrated a high incidence of
      postoperative periprosthetic femoral fracture (PPF) in elderly patients treated
      with 2 commonly used cemented, polished tapered stems. We compared the prevalence
      and incidence rate of PPF in a consecutive cohort of octagenerians with femoral
      neck fractures (FNFs) treated with either a collarless, polished tapered (CPT)
      stem or an anatomic matte stem (Lubinus SP2). Patients and methods - In a
      multicenter, prospective cohort study, we included 979 hips in patients aged 80
      years and above (72% females, median age 86 (80-102) years) with a femoral neck
      fracture as indication for surgery. 69% of the patients were classified as ASA
      class 3 or 4. Hip-related complications and repeat surgery were assessed at a
      median follow-up of 20 (0-24) months postoperatively. Results - 22 hips (2.2%)
      sustained a PPF at a median of 7 (0-22) months postoperatively; 14 (64%) were
      Vancouver B2 fractures. 7 of the 22 surgically treated fractures required
      revision surgery, mainly due to deep infection. The cumulative incidence of PPFs
      was 3.8% in the CPT group, as compared with 0.2% in the SP2 group (p < 0.001).
      The risk ratio (RR) was 16 (95% CI: 2-120) using the SP2 group as denominator.
      Interpretation - The CPT stem was associated with a higher risk of PPF than the
      SP2 stem. We suggest that the tapered CPT stem should not be used for the
      treatment of femoral neck fractures in patients over 80 years.

PMID- 27045319
TI  - The effect of word frequency and parafoveal preview on saccade length during the
      reading of Chinese.
AB  - There are currently 2 theoretical accounts of how readers of Chinese select their
      saccade targets: (a) by moving their eyes to specific saccade targets (i.e., the
      default-targeting hypothesis) and (b) by adjusting their saccade lengths to
      accommodate lexical processing (i.e., the dynamic-adjustment hypothesis). In this
      article, we first report the results of an eye-movement experiment using a gaze
      contingent boundary paradigm. This experiment demonstrates that both target-word
      frequency and its preview validity modulate the lengths of the saccades entering
      and exiting the target words, with longer saccades to/from high-frequency words
      when their preview was available. We then report the results of 2 simulations
      using computational models that instantiate the core theoretical assumptions of
      the default-targeting and dynamic-adjustment hypotheses. Comparisons of these
      simulations indicate that the dynamic-adjustment hypothesis provides a better
      quantitative account of the data from our experiment using fewer free parameters.
      We conclude by discussing evidence for dynamic saccade adjustment during the
      reading of alphabetic languages, and why such a heuristic may be necessary to
      fully explain eye-movement control during the reading of both alphabetic and
      nonalphabetic languages. (PsycINFO Database Record

PMID- 27045320
TI  - The consistency of crossmodal synchrony perception across the visual, auditory,
      and tactile senses.
AB  - Crossmodal judgments of relative timing commonly yield a nonzero point of
      subjective simultaneity (PSS). Here, we test whether subjective simultaneity is
      coherent across all pairwise combinations of the visual, auditory, and tactile
      modalities. To this end, we examine PSS estimates for transitivity: If Stimulus A
      has to be presented x ms before Stimulus B to result in subjective simultaneity,
      and B y ms before C, then A and C should appear simultaneous when A precedes C by
      z ms, where z = x + y. We obtained PSS estimates via 2 different timing judgment
      tasks-temporal order judgments (TOJs) and synchrony judgments (SJs)-thus allowing
      us to examine the relationship between TOJ and SJ. We find that (a) SJ estimates
      do not violate transitivity, and that (b) TOJ and SJ data are linearly related.
      Together, these findings suggest that both TOJ and SJ access the same perceptual
      representation of simultaneity and that this representation is globally coherent
      across the tested modalities. Furthermore, we find that (b) TOJ estimates are
      intransitive. This is consistent with the proposal that while the perceptual
      representation of simultaneity is coherent, relative timing judgments that access
      this representation can at times be incoherent with each other because of
      postperceptual response biases. (PsycINFO Database Record

PMID- 27045321
TI  - The therapeutic potential of royal jelly in benign prostatic hyperplasia.
      Comparison with contemporary literature.
AB  - The aim of this study is to establish the scientific benefit of royal jelly (RJ)
      on prostatic-specific antigen (PSA), post-void residual (PVR) volume and
      International Prostate Symptom Score (IPSS) in benign prostatic hyperplasia. For
      the study, a group of 40 men were administered 38 mg of RJ over a period of three
      months, their PSA values, prostate volumes and the volumes of their transitory
      prostate zones, PVR and IPPS values were measured at the end of the first month,
      and at the end of the third month. The results of this study confirm the
      potential of RJ in reducing PSA scores and improving IPSS values. Since the use
      of RJ did not lead to any significant reduction in PVR, prostate volume, or to
      any involution of the transitory zone, it appears that it may only affect the
      blood marker of prostatic hyperplasia and to improve quality-of-life (QoL) in
      those patients. Overall, in comparison to phytotherapy and conventional therapy,
      RJ had similar positive effects on QoL in patients with BPH, however it exhibited
      markedly better effects on reducing PSA levels in blood. The therapeutical use of
      RJ exhibited no side effects.

PMID- 27045322
TI  - Hemodynamic, Hematological, and Hormonal Responses to Submaximal Exercise in
      Normobaric Hypoxia in Pubescent Girls.
AB  - PURPOSE: The aim of this study was to investigate hemodynamic, hematological, and
      immunological responses to prolonged submaximal cycle ergometer exercise at a
      simulated altitude of 3000 m in pubescent girls. METHODS: Ten girls, 12.8 +/- 1.0
      years old, exercised on a cycle ergometer for 60 min at a work rate corresponding
      to 50% maximal oxygen consumption measured at sea level, under two environmental
      conditions; sea level (normoxia) and a simulated 3000 m altitude (normobaric
      hypoxia). RESULTS: There were no significant differences in tidal volume,
      ventilation, oxygen consumption, cardiac output, stroke volume, and heart rate
      between the two exercise conditions. However, reticulocyte, adrenocorticotropic
      hormone, and cortisol concentrations increased significantly from pre- to
      postexercise in the hypoxic environment. Leukocyte and T-cell count increased and
      B-cell count decreased after exercise under both conditions. There were no
      significant changes in natural killer cell count. CONCLUSION: Our simulated
      hypoxic environment provided a mild environmental stressor that did not impose a
      heavy burden on the cardiovascular, hematological, or immunological functions
      during submaximal exercise in pubescent girls.

PMID- 27045323
TI  - Osteoporosis and vascular calcification in postmenopausal women: a cross
      sectional study.
AB  - Objectives To estimate the correlation between osteoporosis and vascular
      calcification in postmenopausal women and the influence of calcium/vitamin D
      supplements on vascular calcification. Methods A cross-sectional study was
      performed including 29 women with osteoporosis (15 not taking supplements) and 18
      age-matched, non-osteoporotic women. They were evaluated for cardiovascular risk
      factors and blood tests, lateral X-ray of lumbar spine (assessment of abdominal
      aorta calcification, AAC) and carotid ultrasound (increased intima media
      thickness (iIMT) or calcified plaques) were performed. Results In univariate
      analysis, osteoporotic women were 16 times more likely to develop AAC (odds ratio
      (OR) 15.8, 95% confidence interval (CI) 1.9-135.4) and seven times more likely to
      develop iIMT (OR 6.8, 95% CI 1.8-25.4) compared to normal individuals. The odds
      of developing AAC and iIMT were increased each year after menopause (OR 1.11, 95%
      CI 1.01-1.2 and OR 1.18, 95% CI 1.05-1.3, respectively) and with aging (OR 1.27,
      95% CI 1.1-1.47 and OR = 1.17, 95% CI 1.04-1.3, respectively). Calcified plaques
      were significantly correlated with osteoporosis (p = 0.014). In multivariate
      analysis, osteoporosis was an independent risk factor for AAC (OR 13.3, 95% CI
      1.3-134.4) and iIMT (OR 4.7, 95% CI 1.1-19.9). Low doses of supplements did not
      appear to affect vascular calcification (p = 0.6). Conclusions Osteoporosis is
      associated with increased calcification of the abdominal aorta and carotids. Low
      doses of supplements do not appear to cause any increase in vascular
      calcification in osteoporotic women. 

PMID- 27045324
TI  - Electrophysiological evidences of interaction between calcium channels and PA of
      anthrax.

PMID- 27045325
TI  - Multidimensional Approach to the Development of a Mandarin Chinese-Oriented Sound
      Test.
AB  - PURPOSE: Because the Ling six-sound test is based on American English phonemes,
      it can yield unreliable results when administered to non-English speakers. In
      this study, we aimed to improve specifically the diagnostic palette for Mandarin
      Chinese users by developing an adapted version of the Ling six-sound test.
      METHOD: To determine the set of testing sounds, we performed an exhaustive
      acoustic and statistical analysis in which we considered not only the general
      acoustic properties but also the order of acquisition and the inter- and
      intraspeaker variability. RESULTS: Six phonemes (/u, e, a, i, tch, s/) were
      selected as the testing items for the Mandarin Chinese sound test because these
      sounds exhibit a highly compartmentalized frequency specificity, spanning the
      entire Chinese speech spectrum, as well as a relatively low articulatory
      variability and can be acquired fairly early. CONCLUSION: Through adopting
      language-dependent modifications, caregivers and professionals should have a more
      adequate tool to monitor children's auditory access to the full range of Mandarin
      speech sounds.

PMID- 27045326
TI  - Corrigendum.

PMID- 27045328
TI  - A Direct Method for Incorporating Experimental Data into Multiscale Coarse
      Grained Models.
AB  - To extract meaningful data from molecular simulations, it is necessary to
      incorporate new experimental observations as they become available. Recently, a
      new method was developed for incorporating experimental observations into
      molecular simulations, called experiment directed simulation (EDS), which
      utilizes a maximum entropy argument to bias an existing model to agree with
      experimental observations while changing the original model by a minimal amount.
      However, there is no discussion in the literature of whether or not the minimal
      bias systematically and generally improves the model by creating agreement with
      the experiment. In this work, we show that the relative entropy of the biased
      system with respect to an ideal target is always reduced by the application of a
      minimal bias, such as the one utilized by EDS. Using all-atom simulations that
      have been biased with EDS, one can then easily and rapidly improve a bottom-up
      multiscale coarse-grained (MS-CG) model without the need for a time-consuming
      reparametrization of the underlying atomistic force field. Furthermore, the
      improvement given by the many-body interactions introduced by the EDS bias can be
      maintained after being projected down to effective two-body MS-CG interactions.
      The result of this analysis is a new paradigm in coarse-grained modeling and
      simulation in which the "bottom-up" and "top-down" approaches are combined within
      a single, rigorous formalism based on statistical mechanics. The utility of
      building the resulting EDS-MS-CG models is demonstrated on two molecular systems:
      liquid methanol and ethylene carbonate. 

PMID- 27045327
TI  - Relationship between a Centers for Disease Control and Prevention expanded HIV
      testing initiative and past-year testing by race/ethnicity: a multilevel analysis
      of the Behavioral Risk Factor Surveillance System.
AB  - The Centers for Disease Control and Prevention's (CDC) expanded testing
      initiative (ETI) aims to bolster HIV testing among populations disproportionately
      affected by the HIV epidemic by providing additional funding to health
      departments serving these communities. ETI prioritizes testing in clinical
      settings; therefore, we examined the relationship between state-level ETI
      participation and past-year HIV testing among a racially/ethnically diverse
      sample of adult respondents to the 2012 Behavioral Risk Factor Surveillance
      System who accessed health services within the 12 months prior to being
      interviewed. Controlling for individual- and state-level characteristics in a
      multilevel logistic regression model, ETI participation was independently and
      positively associated with past-year testing, but this association varied by
      race/ethnicity. Hispanics had higher odds (adjusted odds ratio [AOR]: 1.49; 95%
      CI: 1.11-2.02) and American Indian/Alaska Natives had lower odds (AOR: 0.66; 95%
      CI: 0.43-0.99) of testing if they resided in states with (vs. without) ETI
      participation. State-level ETI participation did not significantly alter past
      year testing among other racial/ethnic groups. Prioritizing public health
      resources in states most affected by HIV can improve testing patterns, but other
      mechanisms likely influence which racial/ethnic groups undergo testing. 

PMID- 27045329
TI  - Management of anaemia in CKD-the relative importance of erythropoietin and iron.

PMID- 27045330
TI  - White and Gray Matter Volume Changes and Correlation with Visual Evoked Potential
      in Patients with Optic Neuritis: A Voxel-Based Morphometry Study.
AB  - BACKGROUND: The aim of this study was to investigate potential morphological
      alterations of gray and white matter in patients with optic neuritis (ON) and
      their relationship with behavioral performance, using voxel-based morphometry
      (VBM). MATERIAL/METHODS: Twelve (4 males, 8 females) patients with ON and 12 (4
      males, 8 females) age-, sex-, and education-matched healthy controls (HCs)
      underwent magnetic resonance imaging (MRI). Imaging data were analyzed using two
      sample t tests to identify group differences in gray and white matter volume
      (GMV, WMV). Correlation analysis was used to explore relationships between
      observed GMV and WMV of different areas and visual evoked potential (VEP) in ON.
      RESULTS: Compared with HCs, ON patients had: significantly decreased GMV in the
      left postcentral gyrus, left inferior frontal gyrus, left anterior cingulate,
      left and right middle frontal gyrus, and right inferior parietal lobule;
      decreased WMV in the left middle frontal gyrus, right superior frontal gyrus,
      left precentral gyrus and right inferior parietal lobule; and increased WMV in
      the left fusiform gyrus and left inferior parietal lobule. VEP latency of the
      right eye in ON correlated positively with WMV signal value of the left fusiform
      gyrus (r=0.726, p=0.008), and negatively with GMV signal value of the right
      inferior parietal lobule (r=-0.611, p=0.035). Duration of ON correlated
      negatively with WMV signal value of the right superior frontal gyrus (r=-0.662,
      p=0.019), while best-corrected visual acuity (VA) of the right eye correlated
      negatively with WMV signal value of the left middle frontal gyrus (r=-0.704,
      p=0.011). CONCLUSIONS: These results suggest significant brain involvement in ON,
      which may reflect the underlying pathologic mechanism. Correlational results
      demonstrate that VEP in ON is closely associated with WMV and GMV atrophy in many
      brain regions.

PMID- 27045331
TI  - The effect of first trimester subchorionic hematoma on pregnancy outcomes in
      patients underwent IVF/ICSI treatment.
AB  - OBJECTIVE: The aim of this retrospective cohort study was to assess the effect of
      subchorionic hematoma (SCH) on pregnancy outcomes in IVF/ICSI patients. METHODS:
      We retrospectively analyzed 1097 pregnancies achieved by in vitro fertilization
      and embryo transfer (IVF-ET) or frozen-thawed embryo transfers (FETs) between
      January 2013 and June 2013 at the IVF center of Nanjing Drum Tower Hospital. The
      prevalence of SCH was 12.1% in this group (133/1097). We compared the pregnancy
      outcomes between the SCH group and non-SCH group, while the risk factors for SCH
      were also evaluated. RESULTS: There was no significant difference between SCH
      group and non-SCH group with regard to patients' age, spouse's age, endometrial
      thickness, miscarriage rate (5.6% versus 6.2%, p > 0.05), second trimester fetus
      loss rate (5.6% versus 7.7%, p > 0.05) or live birth rate (89.5% versus 86.1%, p
      > 0.05). While the birth weight in singleton pregnancy in SCH group was
      significant lower (3207.8 +/- 595.7 g versus 3349.2 +/- 59.7 g, p = 0.03). SCH
      was more common in fresh embryo transfer patients than that in FET patients
      (16.6% versus 5.1%, p < 0.01), fresh embryo transfer was a high risk for SCH with
      OR 3.67, 95% CI: 2.28-5.90. CONCLUSION: We concluded that SCH was associated with
      lower birth weight in singleton pregnancy, but SCH did not increase pregnancy
      loss rate in IVF/ICSI patients, and fresh embryo transfer may contribute to SCH
      onset.

PMID- 27045332
TI  - Three-Step Synthesis of Fluoranthenes through Pd-Catalyzed Inter- and
      Intramolecular C-H Arylation.
AB  - A three-step synthetic method for the preparation of fluoranthenes, involving
      Miura's intermolecular C-H arylation, nonaflation, and intramolecular C-H
      arylation, has been developed. Various 1-naphthols and haloarenes were
      successfully used as substrates. Reaction conditions that afford high site
      selectivity have been developed for the intramolecular C-H arylation step.

PMID- 27045333
TI  - Comorbidity in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory condition, which is
      associated with an increased risk of comorbidity from other diseases. RA disease
      severity is a major predictor of development of cardiovascular disease, serious
      infections and malignant lymphoma. This reflects the role of chronic inflammation
      in the underlying pathology. Recent surveys indicate that although clinical
      outcomes have improved in patients with RA, mainly owing to access to more
      efficient pharmacotherapy, comorbidity remains a major issue in many patients.
      Register-based observational studies are useful sources of information on the
      impact of comorbidity and the efficacy and safety of antirheumatic treatment in
      patients with coexisting diseases. As a part of strategies to improve further the
      management of patients with RA, multidisciplinary collaboration for prevention
      and early detection of comorbidities is of major importance.

PMID- 27045334
TI  - Lower Detection Probability of Avian Plasmodium in Blood Compared to Other
      Tissues.
AB  - We tested whether the probability of detecting avian haemosporidia (Plasmodium
      and Haemoproteus) using molecular techniques differs among blood, liver, heart,
      and pectoral muscle tissues. We used a paired design, sampling the 4 tissue types
      in 55 individuals of a wild South American suboscine antbird, the white
      shouldered fire-eye (Pyriglena leucoptera). We also identified parasites to
      cytochrome b lineage. Detection probability was significantly lower in blood
      compared to the other 3 tissue types combined. Eight of 22 infections were not
      detected in blood samples; 4-7 infections were not detected in the other
      individual tissues. The same parasite lineage was recovered from different
      tissues.

PMID- 27045339
TI  - Isolation of pristine MXene from Nb4AlC3 MAX phase: a first-principles study.
AB  - Synthesis of pristine MXene sheets from MAX phase is one of the foremost
      challenges in getting a complete understanding of the properties of this new
      technologically important 2D-material. Efforts to exfoliate Nb4AlC3 MAX phase
      always lead to Nb4C3 MXene sheets, which are functionalized and have several Al
      atoms attached. Using the first-principles calculations, we perform an intensive
      study on the chemical transformation of MAX phase into MXene sheets by inserting
      HF, alkali atoms and LiF in Nb4AlC3 MAX phase. Calculated bond-dissociation
      energy (BDE) shows that the presence of HF in MAX phase always results in
      functionalized MXene, as the binding of H with MXene is quite strong while that
      with F is weak. Insertion of alkali atoms does not facilitate pristine MXene
      isolation due to the presence of chemical bonds of almost equal strength. In
      contrast, weak Li-MXene and strong Li-F bonding in Nb4AlC3 with LiF ensured
      strong anisotropy in BDE, which will result in the dissociation of the Li-MXene
      bond. Ab initio molecular dynamics calculations capture these features and show
      that at 500-650 K, the Li-MXene bond indeed breaks leaving a pristine MXene sheet
      behind. The approach and insights developed here for chemical exfoliation of
      layered materials bonded by chemical bonds instead of van der Waals can promote
      their experimental realization. 

PMID- 27045335
TI  - Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics
      simulation and Markov State Model.
AB  - Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold
      into G-quadruplex, which correlates with functionally important genomic
      regionsis. However, unfolding mechanism involved in the structural stability of G
      quadruplex has not been satisfactorily elucidated on experiments so far. Herein,
      we studied the unfolding pathway of TBA by a combination of molecular dynamics
      simulation (MD) and Markov State Model (MSM). Our results revealed that the
      unfolding of TBA is not a simple two-state process but proceeds along multiple
      pathways with multistate intermediates. One high flux confirms some observations
      from NMR experiment. Another high flux exhibits a different and simpler unfolding
      pathway with less intermediates. Two important intermediate states were
      identified. One is similar to the G-triplex reported in the folding of G
      quadruplex, but lack of H-bonding between guanines in the upper plane. More
      importantly, another intermediate state acting as a connector to link the folding
      region and the unfolding one, was the first time identified, which exhibits
      higher population and stability than the G-triplex-like intermediate. These
      results will provide valuable information for extending our understanding the
      folding landscape of G-quadruplex formation. 

PMID- 27045340
TI  - Bacterial community associated to the pine wilt disease insect vectors Monochamus
      galloprovincialis and Monochamus alternatus.
AB  - Monochamus beetles are the dispersing vectors of the nematode Bursaphelenchus
      xylophilus, the causative agent of pine wilt disease (PWD). PWD inflicts
      significant damages in Eurasian pine forests. Symbiotic microorganisms have a
      large influence in insect survival. The aim of this study was to characterize the
      bacterial community associated to PWD vectors in Europe and East Asia using a
      culture-independent approach. Twenty-three Monochamus galloprovincialis were
      collected in Portugal (two different locations); twelve Monochamus alternatus
      were collected in Japan. DNA was extracted from the insects' tracheas for 16S
      rDNA analysis through denaturing gradient gel electrophoresis and barcoded
      pyrosequencing. Enterobacteriales, Pseudomonadales, Vibrionales and
      Oceanospirilales were present in all samples. Enterobacteriaceae was represented
      by 52.2% of the total number of reads. Twenty-three OTUs were present in all
      locations. Significant differences existed between the microbiomes of the two
      insect species while for M. galloprovincialis there were no significant
      differences between samples from different Portuguese locations. This study
      presents a detailed description of the bacterial community colonizing the
      Monochamus insects' tracheas. Several of the identified bacterial groups were
      described previously in association with pine trees and B. xylophilus, and their
      previously described functions suggest that they may play a relevant role in PWD.

PMID- 27045341
TI  - Alkoxy Hydrosilanes As Surrogates of Gaseous Silanes for Hydrosilylation of
      Alkenes.
AB  - Me2SiH2, MeSiH3, and SiH4 are gaseous and flammable silanes that are inconvenient
      to use in chemical reactions. Catalytic amounts of a nickel pincer complex and
      NaO(t)Bu are reported to allow the synthesis of alkyl hydrosilanes from alkenes
      and alkoxy hydrosilanes, leading to the replacement of Me2SiH2, MeSiH3, and SiH4
      by Me2(MeO)SiH, Me(EtO)2SiH, and (MeO)3SiH in hydrosilylation reactions of
      alkenes. The scope and mechanism of the reactions are also described. 

PMID- 27045342
TI  - Higher serum ferritin level and lower femur neck strength in women at the stage
      of bone loss (>= 45 years of age): The Fourth Korea National Health and Nutrition
      Examination Survey (KNHANES IV).
AB  - PURPOSE: Despite the clear effect of iron on bone metabolism, most clinical
      studies related to bone health have only focused on bone mineral density (BMD).
      In the present study, we investigated the relationship between serum ferritin and
      composite indices of femur neck strength via a population-based, cross-sectional
      study using the Korea National Health and Nutrition Examination Survey (KNHANES).
      METHODS: Our study series included 693 women at the stage of bone loss (>= 45
      years of age), defined based on the observed patterns of age-related BMD changes
      in the KNHANES. Geometric bone structure properties, including hip axis length
      (HAL) and femur neck width (FNW), were measured using hip dual-energy X-ray
      absorptiometry scans and were combined with BMD, body weight, and height to
      create composite indices of femur neck strength relative to load in three
      different failure modes: compression (CSI), bending (BSI), and impact strength
      indices (ISI). RESULTS: After adjustment for age, body mass index (BMI),
      lifestyle factors, serum 25-hydroxyvitamin D, calcium and phosphorus intake,
      diabetes, and menopause status, multiple regression analyses revealed that serum
      ferritin was inversely associated with the BMD values at the lumbar spine and
      femur neck, and the femur neck cortical thickness. Importantly, in all adjustment
      models, higher serum ferritin was consistently associated with the lower values
      for all three femur neck composite indices, such as CSI, BSI, and ISI.
      CONCLUSIONS: These data provide the first clinical evidence that increased total
      body iron stores reflected by higher serum ferritin may be associated with the
      decrease of bone strength relative to load.

PMID- 27045343
TI  - Biomass-Based Mechanically Strong and Electrically Conductive Polymer Aerogels
      and Their Application for Supercapacitors.
AB  - A novel biomass-based mechanically strong and electrically conductive polymer
      aerogel was fabricated from aniline and biodegradable pectin. The strong hydrogen
      bonding interactions between polyaniline (PANI) and pectin resulted in a defined
      structure and enhanced properties of the aerogel. All the resultant aerogels
      exhibited self-surppoted 3D nanoporous network structures with high surface areas
      (207-331m(2)/g) and hierarchical pores. The results from electrical conductivity
      measurements and compressive tests revealed that these aerogels also had
      favorable conductivities (0.002-0.1 S/m) and good compressive modulus (1.2-1.4
      MPa). The aerogel further used as electrode for supercapacitors showed enhanced
      capacitive performance (184 F/g at 0.5 A/g). Over 74% of the initial capacitance
      was maintained after repeating 1000 cycles of the cylic voltammetry test, while
      the capacitance retention of PANI was only 57%. The improved electrochemical
      performance may be attributed to the combinative properties of good electrical
      conductivity, BET surface areas, and stable nanoporous structure of the aerogel.
      Thus, this aerogel shows great potential as electrode materials for
      supercapacitors. 

PMID- 27045344
TI  - Sickle red cells as danger signals on proinflammatory gene expression,
      leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear
      cell.
AB  - This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll
      like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3
      (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC).
      TLR and NLRP3 inflammasome could contribute to the maintenance of the
      inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as
      danger signals activating these pathways. In this study, first, we evaluated TLR
      (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1beta and IL-18 expression in
      PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from
      healthy individuals (AA-PBMC). In the second moment, we investigated whether SS
      RBC could interfere with the expression of these molecules in PBMC from healthy
      donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3
      inflammasome expression were investigated by qPCR. IL-1beta, Leukotriene-B4
      (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture
      supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1beta were highly expressed in SS
      PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase
      1, IL-1beta and IL-18 expression and induced IL-1beta, LTB4 and nitrite
      production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome
      expression, but increased TLR2 and IL-18 expression and reduced nitrite
      production. In conclusion, our data suggest that TLR and inflammasome complexes
      may be key inducers of inflammation in SCA patients, probably through SS-RBC;
      also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation,
      indicating the need to develop new therapeutic strategies to SCA patients that
      act with different mechanisms of those observed for HU.

PMID- 27045345
TI  - Rapid Growth of Zinc Oxide Nanotube-Nanowire Hybrid Architectures and Their Use
      in Breast Cancer-Related Volatile Organics Detection.
AB  - A simple direct method for the rapid fabrication of zinc oxide nanotube-nanowire
      hybrid structure in an environmentally friendly way is described here. Zinc foils
      were anodized in an aqueous solution of washing soda and baking soda at room
      temperature in order to obtain the hybrid architecture. At the beginning of the
      process nanowires were formed on the substrate. The wider nanowires transformed
      into nanotubes in about a minute and grew in length with time. The morphological
      integrity was maintained upon heat treatment at temperatures up to the melting
      point of the substrate (~400  degrees C) except that the nanotube wall became
      porous. The chemiresistor devices fabricated using the heat-treated structure
      exhibited high response to low-concentration volatile organic compounds that are
      considered markers for breast cancer. The response was not significantly affected
      by high humidity or presence of hydrogen, methane, or carbon dioxide. The devices
      are expected to find use as breath sensors for noninvasive early detection of
      breast cancer.

PMID- 27045346
TI  - Does aging affect the formation of new topographical memories? Evidence from an
      extensive spatial training.
AB  - A decline in navigational abilities is a consistent feature of aging. Although
      many studies focused on recall of navigational information, the impact of time
      and type of learning on recall has received little attention. We submitted older
      adults and young participants to an extensive training of an ecological
      environment, from both route and survey perspectives. Then, we tested
      participants' learning using from both route and survey perspectives. Although
      older adults benefit from the extensive training, they did not reach the same
      performance of the young participants. Despite this main effect of age, the
      effect of the type of learning was the same in the two groups. Congruence between
      type of learning and recall led to better performance in both groups. We discuss
      these findings in the light of cognitive models of human navigation and aging.
      Useful suggestions about how these findings may inform a specific cognitive
      intervention in older adults are also provided.

PMID- 27045347
TI  - Zwitterionic surface grafting of epoxylated sulfobetaine copolymers for the
      development of stealth biomaterial interfaces.
AB  - Most biomaterials have a lack of a simple, efficient and robust antifouling
      modification approach that limits their potential for biomedical applications.
      The challenge is to develop a universal surface grafting solution to meet the
      antifouling requirement. In this work, a new formulation of zwitterionic
      sulfobetaine-based copolymer, ploy(glycidyl methacrylate-co-sulfobetaine
      methacrylate) (poly(GMA-co-SBMA)), is designed as a chemical for grafting onto
      material and is introduced for the surface zwitterionization of versatile
      biomaterials, including ceramic, metal, and plastics. The grafting principle used
      to stabilize the poly(GMA-co-SBMA) on the target surfaces is based the base
      induced ring opening reaction between epoxied and hydroxyl groups. A universal
      surface modification procedure was developed and performed from an optimized
      sequence of ultra-violet ozone pretreatment and trimethylamine-catalyzed
      zwitterionization on a selective case of versatile surfaces including silicon
      wafer, ceramic glass, titanium, steel, and polystyrene. The prepared poly(GMA-co
      SBMA) with an optimum PGMA/PSBMA ratio of 0.23 and a molecular weight of 25kDa
      exhibited the best resistance to fibrinogen adsorption with over 90% reduction as
      well as blood cell activation, tissue cell adhesion and bacterial attachment on
      the zwitterionic copolymer grafted surfaces. The developed antifouling grafting
      introduces a universal modification method to generate zwitterionic interfaces on
      versatile biomaterial substrates, providing great potential for application in
      medical device coating. STATEMENT OF SIGNIFICANCE: A simple, efficient and robust
      antifouling modification approach is critical for many scientific interests and
      industrial applications. In current stage, the existing available zwitterionic
      modifications suffer from the lack of universal surface grafting solution to
      achieve the antifouling requirement on versatile biomaterial substrates. In this
      study, we synthesized and characterized a new zwitterionic sulfobetaine-based
      copolymer, ploy(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co
      SBMA)), which is designed as chemical grafting onto material and introduced for
      the surface zwitterionization of versatile biomaterials, including ceramic,
      metal, and plastics. This research have a promising opportunity for the
      application of stealth biomaterial interfaces on the next generation of medical
      devices.

PMID- 27045348
TI  - Shape-controlled high cell-density microcapsules by electrodeposition.
AB  - Cell encapsulation within alginate-poly-l-lysine (PLL) microcapsules has been
      developed to provide a miniaturized three-dimensional (3D) microenvironment with
      an aqueous core while promoting development of encapsulated cells into high cell
      density structures. In this paper, a novel method for fabricating shape
      controlled alginate-PLL microcapsules to construct 3D cell structures based on
      electrodeposition method is provided. Two-dimensional Ca-alginate cell-laden gel
      membranes were electrodeposited onto a micro-patterned electrode and further
      detached from the electrode. The PLL was coated onto the gel structures to form
      alginate-PLL complex as an outer shell and sodium citric solution was utilized to
      melt the internal alginate to achieve miniaturized 3D microcapsules (sphere,
      cuboid, and rod shape). By this proposed method, rat liver cells (RLC-18) formed
      multi-cellular aggregates with high cell-density after cultivation for 2weeks.
      STATEMENT OF SIGNIFICANCE: The use of alginate-poly-l-lysine (PLL) microcapsules
      has shown great potential in fabricating 3D cell structures with high cell
      density. Despite their success related to their ability to provide a miniaturized
      microenvironment with an aqueous core, alginate-PLL microcapsules has drawback
      such as a limited shape-control ability. Because of the mechanism of Ca-induced
      alginate gel formation, it is still difficult to precisely control the gelation
      process to produce alginate-PLL microcapsules with specific shape. The present
      study provides an electrodeposition-based method to generate shape-controlled
      microcapsules for 3D cell structures. Sphere, cuboid, and rod shaped
      microcapsules of RLC-18 cells were produced for long-term culture to obtain
      desired morphologies of cell aggregates.

PMID- 27045349
TI  - Recent advances in bulk metallic glasses for biomedical applications.
AB  - With a continuously increasing aging population and the improvement of living
      standards, large demands of biomaterials are expected for a long time to come.
      Further development of novel biomaterials, that are much safer and of much higher
      quality, in terms of both biomedical and mechanical properties, are therefore of
      great interest for both the research scientists and clinical surgeons. Compared
      with the conventional crystalline metallic counterparts, bulk metallic glasses
      have unique amorphous structures, and thus exhibit higher strength, lower Young's
      modulus, improved wear resistance, good fatigue endurance, and excellent
      corrosion resistance. For this purpose, bulk metallic glasses (BMGs) have
      recently attracted much attention for biomedical applications. This review
      discusses and summarizes the recent developments and advances of bulk metallic
      glasses, including Ti-based, Zr-based, Fe-based, Mg-based, Zn-based, Ca-based and
      Sr-based alloying systems for biomedical applications. Future research directions
      will move towards overcoming the brittleness, increasing the glass forming
      ability (GFA) thus obtaining corresponding bulk metallic glasses with larger
      sizes, removing/reducing toxic elements, and surface modifications. STATEMENT OF
      SIGNIFICANCE: Bulk metallic glasses (BMGs), also known as amorphous alloys or
      liquid metals, are relative newcomers in the field of biomaterials. They have
      gained increasing attention during the past decades, as they exhibit an excellent
      combination of properties and processing capabilities desired for versatile
      biomedical implant applications. The present work reviewed the recent
      developments and advances of biomedical BMGs, including Ti-based, Zr-based, Fe
      based, Mg-based, Zn-based, Ca-based and Sr-based BMG alloying systems. Besides,
      the critical analysis and in-depth discussion on the current status, challenge
      and future development of biomedical BMGs are included. The possible solution to
      the BMG size limitation, the brittleness of BMGs has been proposed.

PMID- 27045350
TI  - Conjugates of small targeting molecules to non-viral vectors for the mediation of
      siRNA.
AB  - To use siRNA (small interfering RNA) for gene therapy, a gene delivery system is
      often necessary to overcome several challenging requirements including rapid
      excretion, low stability in blood serum, non-specific accumulation in tissues,
      poor cellular uptake and inefficient intracellular release. Active and/or passive
      targeting should help the delivery system to reach the desired tissue or cell, to
      be internalized, and to deliver siRNA to the cytoplasm so that siRNA can inhibit
      protein synthesis. This review covers conjugates of small targeting molecules and
      non-viral delivery systems for the mediation of siRNA, with a focus on their
      transfection properties in order to help the development of new and efficient
      siRNA delivery systems, as the therapeutic solutions of tomorrow. STATEMENT OF
      SIGNIFICANCE: The delivery of siRNA into cells or tissues remains to be a
      challenge for its applications, an alternative strategy for siRNA delivery
      systems is direct conjugation of non-viral vectors with targeting moieties for
      cellular delivery. In comparison to macromolecules, small targeting molecules
      have attracted great attention due to their many potential advantages including
      significant simplicity and ease of production, good repeatability and
      biodegradability. This review will focus on the most recent advances in the
      delivery of siRNA using conjugates of small targeting molecules and non-viral
      delivery systems. Based the editor's suggestions, we hope the revised manuscript
      could provide more profound understanding to the conjugates of targeting
      molecules to vectors for mediation of siRNA.

PMID- 27045351
TI  - The effects of hypoxia on in vitro culture of dental-derived stem cells.
AB  - The culture of cells under hypoxia is considered one of the hot topics of tissue
      engineering, especially when exploring the proliferation capacity, a critical
      step for cellular-based therapies. The use of in vitro hypoxic environment aims
      to simulate the oxygen concentrations found in stem cell niches. Dental tissues
      are attractive sources of stem cells, as they are obtained from discarded tissue,
      after third molar extraction and exfoliation deciduous teeth, respectively.
      However, small amounts of cells are obtained from these sources. Thus, optimizing
      the in vitro conditions for proliferation and differentiation of these cells is
      essential for future regenerative strategies. This review presents a summary of
      the results regarding the effect of hypoxia on dental-derived stem cells after an
      electronic search on PubMed databases. The studies show increased differentiation
      potential and paracrine action of dental-derived stem cells under hypoxic
      environment. There are controversies related to proliferation of dental-derived
      stem cells under induced hypoxia. The lack of standardization in cell culture
      techniques contributes to these biases and future studies should describe in more
      detail the protocols used. The knowledge regarding the effect of hypoxia on
      dental-derived stem cells needs further clarification for assisting the clinical
      application of these cells. 

PMID- 27045352
TI  - Structure of Enhanced Cued Recall Task in the 7 Minute Screen Test.
AB  - Episodic memory in the 7 Minute Screen is assessed by the Enhanced Cued Recall
      (ECR) test. The ECR test is composed of three phases, Identification, Immediate
      Recall, and Free and Cued Recall. However, just the last phase is considered for
      the total score. We believe that collecting the performance data of the
      Identification and Immediate Recall phases could provide information regarding
      possible difficulties or impairments in the different aspects involved in the
      temporal mnesic process of acquisition of new information, such as in working
      memory or visual identification. The objective was to assess the goodness of fit
      for the three phases of the ECR test using a Confirmatory Factor Analysis (CFA)
      to show if each phase is separated from each other as a different aspect that
      participates in the mnesic process. A total of 311 participants greater than 65
      years were included in this study. Confirmatory factor analyses were conducted
      for each individual phase. The analyses show that the ECR test consists of three
      separate phases that identify different steps of the mnesic process. Individual
      scores for each phase could allow for investigation of patient performance in
      different aspects of the memory process and could help in further
      neuropsychological assessment.

PMID- 27045353
TI  - An Unusual Cause of Large-Bowel Obstruction: Cholecystocolonic Fistula and
      Gallstone Ileus.

PMID- 27045354
TI  - Mucosal Healing in the Treatment of Ulcerative Colitis: A Reliable Target?

PMID- 27045355
TI  - Comprehensive Genome-Wide Transcriptomic Analysis of Immature Articular Cartilage
      following Ischemic Osteonecrosis of the Femoral Head in Piglets.
AB  - OBJECTIVE: Ischemic osteonecrosis of the femoral head (ONFH) in piglets results
      in an ischemic injury to the immature articular cartilage. The molecular changes
      in the articular cartilage in response to ONFH have not been investigated using a
      transcriptomic approach. The purpose of this study was to perform a genome-wide
      transcriptomic analysis to identify genes that are upregulated in the immature
      articular cartilage following ONFH. METHODS: ONFH was induced in the right
      femoral head of 6-week old piglets. The unoperated femoral head was used as the
      normal control. At 24 hours (acute ischemic-hypoxic injury), 2 weeks (avascular
      necrosis in the femoral head) and 4 weeks (early repair) after surgery (n = 4
      piglets/time point), RNA was isolated from the articular cartilage of the femoral
      head. A microarray analysis was performed using Affymetrix Porcine GeneChip
      Array. An enrichment analysis and functional clustering of the genes upregulated
      due to ONFH were performed using DAVID and STRING software, respectively. The
      increased expression of selected genes was confirmed by a real-time qRTPCR
      analysis. RESULTS: Induction of ONFH resulted in the upregulation of 383 genes at
      24 hours, 122 genes at 2 weeks and 124 genes at 4 weeks compared to the normal
      controls. At 24 hours, the genes involved in oxidoreductive, cell-survival, and
      angiogenic responses were significantly enriched among the upregulated genes.
      These genes were involved in HIF-1, PI3K-Akt, and MAPK signaling pathways. At 2
      weeks, secretory and signaling proteins involved in angiogenic and inflammatory
      responses, PI3K-Akt and matrix-remodeling pathways were significantly enriched.
      At 4 weeks, genes that represent inflammatory cytokines and chemokine signaling
      pathways were significantly enriched. Several index genes (genes that are
      upregulated at more than one time point following ONFH and are known to be
      important in various biological processes) including HIF-1A, VEGFA, IL-6, IL6R,
      IL-8, CCL2, FGF2, TGFB2, MMP1, MMP3, ITGA5, FN and Col6A1 were upregulated in the
      immature articular cartilage following ONFH. A qRTPCR analysis of selected genes
      confirmed the upregulated expression observed in the microarray analysis.
      CONCLUSION: Immature articular cartilage responds to ONFH by the upregulation of
      genes involved in hypoxic stress response, angiogenesis, matrix remodeling and
      inflammation. This study provides novel insights into the multi-faceted role of
      immature articular cartilage, with inflammation as a key component, following
      ONFH in piglets.

PMID- 27045356
TI  - Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after
      cerebral ischemia.
AB  - Intense efforts are being undertaken to understand the pathobiology of ischemia
      and to develop novel and effective treatments. Angiotensin II type 2 receptor
      (AT2R) is related with a beneficial role in neurodegenerative disorders,
      including ischemia. However, the underlying molecular mechanism remains elusive.
      In this study, we have established that AT2R stimulation by C21 compound, a
      specific AT2R agonist, caused a VEGF upregulation. Using mouse primary cortical
      neurons exposed to oxygen-glucose deprivation (OGD), we established that this
      effect was mediated by a mechanism dependent of mTORC1 signaling since mTOR
      inhibition abolished the C21-induced VEGF upregulation. Also, we have temporally
      characterized the changes on VEGF levels after ischemia induction in rats using
      two different approaches: transient and permanent middle cerebral artery
      occlusion (tMCAO and pMCAO). VEGF levels were permanently augmented after
      reperfusion (tMCAO) whereas lower levels of VEGF were found after pMCAO,
      remarkably at 21days. Therefore, C21 compound accelerated the recovery of the
      neurological status of pMCAO rats, reduced the ischemic damage area and abolished
      pMCAO-induced VEGF downregulation at 21days. This effect of C21 compound was
      mainly observed in neurons of the peri-infarct area. Our results suggest that a
      C21-induced VEGF upregulation may be crucial after an ischemic neuronal insult in
      both of our experimental approaches. This upregulation was mediated by a
      mechanism dependent of Akt/mTOR signaling pathway, since mTOR inhibition
      abolished the VEGF upregulation induced by C21. Considering that VEGF is involved
      in regenerative processes, we propose that AT2R activation could be used as a
      potential pharmacological strategy after ischemic stroke.

PMID- 27045357
TI  - Synthesis and evaluation of condensed magnetic nanocrystal clusters with in vivo
      multispectral optoacoustic tomography for tumour targeting.
AB  - Colloidal clusters of magnetic iron oxide nanocrystals (MIONs), particularly in
      the condensed pattern (co-CNCs), have emerged as new superstructures to improve
      further the performance of MIONs in applications pertaining to magnetic
      manipulation (drug delivery) and magnetic resonance imaging (MRI). Exploitation
      of the advantages they represent and their establishment in the area of
      nanomedicine demands a particular set of assets. The present work describes the
      development and evaluation of MION-based co-CNCs featuring for the first time
      such assets: High magnetization, as well as magnetic content and moment, high
      relaxivities (r2 = 400 and r2* = 905 s(-1) mMFe(-1)) and intrinsic loss power
      (2.3 nH m(2) kgFe(-1)) are combined with unprecedented colloidal stability and
      structural integrity, stealth and drug-loading properties. The reported
      nanoconstructs are endowed with additional important features such as cost
      effective synthesis and storage, prolonged self-life and biocompatibility. It is
      finally showcased with in vivo multispectral optoacoustic tomography how these
      properties culminate in a system suitable for targeting breast cancer and for
      forceful in vivo manipulation with low magnetic field gradients.

PMID- 27045358
TI  - The spatiotemporal hormonal orchestration of human folliculogenesis, early
      embryogenesis and blastocyst implantation.
AB  - The early reproductive events starting with folliculogenesis and ending with
      blastocyst implantation into the uterine endometrium are regulated by a complex
      interplay among endocrine, paracrine and autocrine factors. This review examines
      the spatiotemporal integration of these maternal and embryonic signals that are
      required for successful reproduction. In coordination with hypothalamic-pituitary
      gonadal (HPG) hormones, an intraovarian HPG-like axis regulates folliculogenesis,
      follicular quiescence, ovulation, follicular atresia, and corpus luteal
      functions. Upon conception and passage of the zygote through the fallopian tube,
      the contribution of maternal hormones in the form of paracrine secretions from
      the endosalpinx to embryonic development declines, with autocrine and paracrine
      signaling becoming increasingly important as instructional signals for the
      differentiation of the early zygote/morula into a blastocyst. These maternal and
      embryonic signals include activin and gonadotropin-releasing hormone 1 (GnRH1)
      that are crucial for the synthesis and secretion of the 'pregnancy' hormone human
      chorionic gonadotropin (hCG). hCG in turn signals pre-implantation embryonic cell
      division and sex steroid production required for stem cell differentiation, and
      subsequent blastulation, gastrulation, cavitation and blastocyst formation. Upon
      reaching the uterus, blastocyst hatching occurs under the influence of decreased
      activin signaling, while the attachment and invasion of the trophoblast into the
      endometrium appears to be driven by a decrease in activin signaling, and by
      increased GnRH1 and hCG signaling that allows for tissue remodeling and the
      controlled invasion of the blastocyst into the uterine endometrium. This review
      demonstrates the importance of integrative endocrine, paracrine, and autocrine
      signaling for successful human reproduction.

PMID- 27045359
TI  - A high-yield synthesis of [m]biphenyl-extended pillar[n]arenes for an efficient
      selective inclusion of toluene and m-xylene in the solid state.
AB  - [m]Bp-ExPn with a rigid and nanometer-sized cavity, as an extended version of
      pillar[n]arene by replacing 1,4-dimethoxybenzene monomers with biphenyl entities,
      was synthesized for the first time. Intriguingly, toluene and m-xylene can be
      stably included within the cavity of [2]Bp-ExP6, which endows these newly
      developed synthetic receptors with great potential in the purification of
      petrochemicals. 

PMID- 27045360
TI  - Development of a loop-mediated isothermal amplification method for rapid
      detection of streptococcal pyrogenic exotoxin B.
AB  - We developed a visual loop-mediated isothermal amplification (LAMP) technique to
      detect the streptococcal pyrogenic exotoxin B (speB) gene. Fifteen strains (from
      American Type Culture Collection or clinical isolates) were used to determine the
      specificity and sensitivity of the LAMP assay. Clinical samples were collected
      from 132 patients with suspected Streptococcus pyogenes (S. pyogenes) infection
      to verify the feasibility of the LAMP assay for detection of the speB gene. By
      using a set of five primers (a pair of outer primers, a pair of inner primers and
      one loop primer) targeting the speB gene, the amplification reaction was rapidly
      performed in a regular water bath under isothermal conditions at 63  degrees C
      for approximately 60 min. Only the two S. pyogenes strains showed positive
      results which were easily observed with the naked eye, and the other strains
      showed negative results. The detection limit of the LAMP assay was 0.01 ng/MUl of
      template, showing higher sensitivity than conventional PCR (with a detection
      limit of 1.0 ng/MUl). The detection rate of the speB gene in clinical samples was
      71.21% and was consistent with the PCR results. The rapid detection of the speB
      gene by the LAMP assay is highly specific and sensitive, is simple to perform and
      cost-effective, and is expected to be a new reliable method for the rapid
      diagnosis of S. pyogenes infection, that is particularly suitable for rural or
      community hospitals in developing countries. 

PMID- 27045361
TI  - Accumulation, transformation and breakdown of DSP toxins from the toxic
      dinoflagellate Dinophysis acuta in blue mussels, Mytilus edulis.
AB  - Okadaic acid (OA), dinophysistoxins (DTX) and pectenotoxins (PTX) produced by the
      dinoflagellates Dinophysis spp. can accumulate in shellfish and cause diarrhetic
      shellfish poisoning upon human consumption. Shellfish toxicity is a result of
      algal abundance and toxicity as well as accumulation and depuration kinetics in
      mussels. We mass-cultured Dinophysis acuta containing OA, DTX-1b and PTX-2 and
      fed it to the blue mussel, Mytilus edulis under controlled laboratory conditions
      for a week to study toxin accumulation and transformation. Contents of OA and DTX
      1b in mussels increased linearly with incubation time, and the net toxin
      accumulation was 66% and 71% for OA and DTX-1b, respectively. Large proportions
      (~50%) of both these toxins were transformed to fatty acid esters. Most PTX-2 was
      transformed to PTX-2 seco-acid and net accumulation was initially high, but
      decreased progressively throughout the experiment, likely due to esterification
      and loss of detectability. We also quantified depuration during the subsequent
      four days and found half-life times of 5-6 days for OA and DTX-1b. Measurements
      of dissolved toxins revealed that depuration was achieved through excreting
      rather than metabolizing toxins. This is the first study to construct a full mass
      balance of DSP toxins during both accumulation and depuration, and we demonstrate
      rapid toxin accumulation in mussels at realistic in situ levels of Dinophysis.
      Applying the observed accumulation and depuration kinetics, we model mussel
      toxicity, and demonstrate that a concentration of only 75 Dinophysis cells l(-1)
      is enough to make 60 mm long mussels exceed the regulatory threshold for OA
      equivalents. 

PMID- 27045362
TI  - Red-bellied black snake (Pseudechis porphyriacus) envenomation in the dog:
      Diagnosis and treatment of nine cases.
AB  - The clinical signs, biochemical changes and serum and urine venom concentrations
      for a series of nine cases of Red bellied black snake [RBBS] (Pseudechis
      porphyriacus) envenomation in eight dogs seen in a regional Australian veterinary
      hospital are described. Although the resulting envenomation syndrome was, in most
      cases, relatively mild and responded rapidly to intravenous administration of a
      novel bivalent caprylic acid purified whole IgG equine antivenom for tiger
      (Notechis scutatus) and brown snake (Pseudonaja textilis), one fatality prior to
      antivenom treatment was recorded. The latter case occurred within 1 h of
      envenomation prior to receiving antivenom treatment. Intravascular haemolysis,
      pigmenturia, bite site swelling, lethargy, and generally mild coagulopathy were
      present in most cases. Detectable RBBS venom specific components were found in
      serum, bite site swab or urine using a standard sandwich ELISA approach. Serum
      levels fell within the range previously reported for human RBBS envenomation
      cases (6-79 ng/ml) whilst bite site and urine samples varied more markedly (8.2
      to >5000 ng/ml and 2.2-1300 ng/ml respectively). No venom was detected from serum
      after antivenom treatment. The envenomation syndrome in dogs is similar to what
      is described for humans, with the exception of the presence of potentially severe
      venom induced consumption coagulopathy in one case (aPTT > 300 s and fibrinogen <
      0.43 g/L) and potential for fatal outcomes. This series represents the largest
      and most detailed examination of RBBS envenomation in animals yet reported. It
      reinforces the emerging view that the potential severity of this envenomation has
      been underappreciated by veterinary practitioners and highlights the possibility
      of severe venom induced consumption coagulopathy in canine cases. 

PMID- 27045363
TI  - Micrurus snake species: Venom immunogenicity, antiserum cross-reactivity and
      neutralization potential.
AB  - Micrurus snakebites can cause death by muscle paralysis and respiratory arrest a
      few hours after envenomation. The specific treatment for these snake
      envenomations is the intravenous application of heterologous antivenom. In
      Brazil, this antivenom is produced from horses that are immunized with a mixture
      of Micrurus corallinus and Micrurus frontalis venoms, which are snakes that
      inhabit the south and southeastern regions of the country. Previously, we
      demonstrated that the coral antivenom, which is used in human therapy, was not
      able to neutralize several of the toxic venom effects from some Micrurus species
      that inhabit the country, as measured by in vitro and in vivo assays. The present
      study aimed to investigate the immunogenic properties of Micrurus spp. venoms, as
      well as the cross-reactivity and neutralization potential of experimental
      monovalent and polyvalent sera that were produced in different animal species.
      The present data showed that Micrurus venoms exhibited the same immunogenicity
      pattern in the three utilized animal species and that the specific antisera
      presented a large cross-reactivity when analyzed with ELISA and Western blot
      assays. Nonetheless, these positive results were not well correlated with the
      neutralizing potential of the antisera. Thus, the establishment of a new
      antigenic mixture to produce novel more efficient therapeutic Micrurus antivenom
      is not a simple task. Further studies, particularly with the Micrurus
      lemniscatus, Micrurus altirostris and Micrurus surinamensis venoms, are necessary
      to establish new strategies for the production of antivenoms with broad
      neutralizing activity for the treatment of accidents involving coral snakes
      throughout the country. 

PMID- 27045364
TI  - Severe Fever with Thrombocytopenia Syndrome Virus Antigen Detection Using
      Monoclonal Antibodies to the Nucleocapsid Protein.
AB  - BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne
      infectious disease with a high case fatality rate, and is caused by the SFTS
      virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA
      level in sera of patients with SFTS is known to be strongly associated with
      outcomes. Virological SFTS diagnosis with high sensitivity and specificity are
      required in disease endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: We generated
      novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and
      developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay
      (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody
      as capture and detection antibodies, respectively. The Ag-capture system was
      capable of detecting at least 350-1220 TCID50/100 MUl/well from the culture
      supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in
      SFTS diagnosis was evaluated using serum samples collected from patients
      suspected of having SFTS in Japan. All 24 serum samples (100%) containing high
      copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag
      capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy
      numbers of viral RNA (<105 copies/ml) showed a negative reaction in the Ag
      capture ELISA. Among these Ag-capture ELISA-negative 12 samples, 9 (75%) were
      positive for IgG antibodies against SFTSV. CONCLUSIONS: The newly developed Ag
      capture ELISA is useful for SFTS diagnosis in acute phase patients with high
      levels of viremia.

PMID- 27045365
TI  - Explaining premunition with Kin selection using Haemonchus contortus.
AB  - Premunition is the state in a disease where an existing infection protects the
      host from reinfection with the same species. The cause of premunition is not
      clearly understood. In this study, we hypothesized that kin-selection might be a
      contributing factor in premunition. To test this theory, sheep were infected
      either once with a linguiform or smooth vulval morphotype of Haemonchos
      contortus, twice with the same morphotype or twice with different morphotypes.
      All infections resulted in a similar number of adult parasites. However, there
      were differences in the morphotypes recovered providing potential evidence of kin
      selection. Negative interference competition might also contribute to the
      reduction of the incoming population. Allelopathic or physical interactions
      between the parasites may be the mechanism behind the observed phenomena.

PMID- 27045366
TI  - Expression of Estrogen Receptor Coactivator Proline-, Glutamic Acid- and Leucine
      Rich Protein 1 within Paraspinal Muscles in Adolescents with Idiopathic
      Scoliosis.
AB  - PURPOSE: The aim of this study was to detect and assess the estrogen receptor
      (ESR) coactivator PELP1 expression within human paraspinal skeletal muscles in
      patients suffering from idiopathic scoliosis. METHODS: During surgical correction
      of scoliosis the muscle biopsies harvested in 29 females. Presence of PELP1, ESR1
      and ESR2 genes transcripts was studied using RT-qPCR technique while
      immunohistochemistry and western blot methods were used to detect the PEPL1
      protein presence. RESULTS: PELP1 expression in deep paraspinal muscles revealed
      higher than in superficial back muscles (p = 0.005). Positive immunohistochemical
      staining for PELP1 was observed in the nuclei of the paraspinal muscle cells.
      Western blot revealed PELP1 protein in all samples. No significant difference in
      PELP1 expression between the convex and the concave scoliosis side (p>0.05) was
      found. In deep paraspinal back muscles, a significant correlation between the
      PELP1 expression level on the concave side and the Cobb angle (r = 0.4; p<0.05)
      was noted as well as between the PELP1 and ESR1 expression level (r = 0.7;
      p<0.05) while no correlation between PELP1 and ESR2 expression level was found.
      CONCLUSION: To our knowledge, three techniques for the first time demonstrated
      the presence of the PELP1 in paraspinal muscles of patients with idiopathic
      scoliosis. The PELP1 potential regulatory impact on back muscle function is to be
      further investigated.

PMID- 27045367
TI  - Naringenin Inhibits Superoxide Anion-Induced Inflammatory Pain: Role of Oxidative
      Stress, Cytokines, Nrf-2 and the NO-cGMP-PKG-KATP Channel Signaling Pathway.
AB  - In the present study, the effect and mechanism of action of the flavonoid
      naringenin were evaluated in superoxide anion donor (KO2)-induced inflammatory
      pain in mice. Naringenin reduced KO2-induced overt-pain like behavior, mechanical
      hyperalgesia, and thermal hyperalgesia. The analgesic effect of naringenin
      depended on the activation of the NO-cGMP-PKG-ATP-sensitive potassium channel
      (KATP) signaling pathway. Naringenin also reduced KO2-induced neutrophil
      recruitment (myeloperoxidase activity), tissue oxidative stress, and cytokine
      production. Furthermore, naringenin downregulated KO2-induced mRNA expression of
      gp91phox, cyclooxygenase (COX)-2, and preproendothelin-1. Besides, naringenin
      upregulated KO2-reduced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) mRNA
      expression coupled with enhanced heme oxygenase (HO-1) mRNA expression. In
      conclusion, the present study demonstrates that the use of naringenin represents
      a potential therapeutic approach reducing superoxide anion-driven inflammatory
      pain. The antinociceptive, anti-inflammatory and antioxidant effects are mediated
      via activation of the NO-cGMP-PKG-KATP channel signaling involving the induction
      of Nrf2/HO-1 pathway. 

PMID- 27045368
TI  - Effects of P addition on plant C:N:P stoichiometry in an N-limited temperate
      wetland of Northeast China.
AB  - Phosphorus (P) enrichment induced by anthropogenic activities results in modified
      plant nutrient status, which potentially alters the stoichiometry of carbon (C),
      nitrogen (N), and P in plants. However, how increased P availability changes
      plant C:N:P stoichiometry at different hierarchical scales is unclear in N
      limited ecosystems. In this study, we conducted a four-level P addition
      experiment (0, 1.2, 4.8, and 9.6gPm(-)(2)year(-1)) to elucidate the effect of P
      enrichment on plant C:N:P stoichiometric ratios at both the species and community
      levels in a freshwater wetland in the Sanjiang Plain, Northeast China. We found
      that species- and community-level plant C:N:P stoichiometry responded
      consistently to six years of P addition, although there was a shift in species
      dominance. Phosphorus addition increased plant N and P concentrations and thus
      decreased C:N, C:P, and N:P ratios irrespective of the P addition levels. These
      similar change trends at different scales resulted from the identical responses
      of plant N and P concentrations in different species to P addition. Moreover,
      plant N concentration exhibited an increasing trend with increasing P addition
      levels, whereas plant C:N ratio showed a declining trend. At the community level,
      P addition at the rates of 1.2, 4.8, and 9.6gPm(-2)year(-1) decreased the C:N
      ratio by 24%, 27%, and 34%; decreased the C:P ratio by 33%, 35%, and 38%; and
      decreased the N:P ratio by 12%, 10%, and 6%, respectively. Our results indicate
      that the stoichiometric responses to P addition are scale-independent, and
      suggest that altered plant C:N:P stoichiometry induced by P enrichment would
      stimulate organic matter decomposition and accelerate nutrient cycles in N
      limited temperate freshwater wetlands.

PMID- 27045369
TI  - Early Weightbearing and Range of Motion Versus Non-Weightbearing and
      Immobilization After Open Reduction and Internal Fixation of Unstable Ankle
      Fractures: A Randomized Controlled Trial.
AB  - OBJECTIVES: The aim of this study was to compare early weightbearing and range of
      motion (ROM) to nonweightbearing and immobilization in a cast after surgical
      fixation of unstable ankle fractures. DESIGN: Multicentre randomized controlled
      trial. SETTING: Two-level one trauma centers. PATIENTS: One hundred ten patients
      who underwent open reduction and internal fixation of an unstable ankle fracture
      were recruited and randomized. INTERVENTION: One of 2 rehabilitation protocols:
      (1) Early weightbearing (weightbearing and ROM at 2 weeks, Early WB) or (2) Late
      weightbearing (nonweightbearing and cast immobilization for 6 weeks, Late WB).
      MAIN OUTCOME MEASUREMENTS: The primary outcome measure was time to return to work
      (RTW). Secondary outcome measures included: ankle ROM, SF-36 heath outcome
      scores, Olerud/Molander ankle function score, and rates of complications.
      RESULTS: There was no difference in RTW. At 6 weeks postoperatively, patients in
      the Early WB group had significantly improved ankle ROM (41 vs. 29, P < 0.0001);
      Olerud/Molander ankle function scores (45 vs. 32, P = 0.0007), and SF-36 scores
      on both the physical (51 vs. 42, P = 0.008) and mental (66 vs. 54, P = 0.0008)
      components. There were no differences with regard to wound complications or
      infections and no cases of fixation failure or loss of reduction. Patients in the
      Late WB group had higher rates of planned/performed hardware removal due to plate
      irritation (19% vs. 2%, P = 0.005). CONCLUSIONS: Given the convenience for the
      patient, early improved functional outcome, and the lack of an increased
      complication rate, we recommend early postoperative weightbearing and ROM in
      patients with surgically treated ankle fractures. LEVEL OF EVIDENCE: Therapeutic
      Level I. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 27045370
TI  - Bayesian Monitoring of Emerging Infectious Diseases.
AB  - We define data analyses to monitor a change in R, the average number of secondary
      cases caused by a typical infected individual. The input dataset consists of
      incident cases partitioned into outbreaks, each initiated from a single index
      case. We split the input dataset into two successive subsets, to evaluate two
      successive R values, according to the Bayesian paradigm. We used the Bayes factor
      between the model with two different R values and that with a single R value to
      justify that the change in R is statistically significant. We validated our
      approach using simulated data, generated using known R. In particular, we found
      that claiming two distinct R values may depend significantly on the number of
      outbreaks. We then reanalyzed data previously studied by Jansen et al. [Jansen et
      al. Science 301 (5634), 804], concerning the effective reproduction number for
      measles in the UK, during 1995-2002. Our analyses showed that the 1995-2002
      dataset should be divided into two separate subsets for the periods 1995-1998 and
      1999-2002. In contrast, Jansen et al. take this splitting point as input of their
      analysis. Our estimated effective reproduction numbers R are in good agreement
      with those found by Jansen et al. In conclusion, our methodology for detecting
      temporal changes in R using outbreak-size data worked satisfactorily with both
      simulated and real-world data. The methodology may be used for updating R in real
      time, as surveillance outbreak data become available. 

PMID- 27045371
TI  - Epistasis Test in Meta-Analysis: A Multi-Parameter Markov Chain Monte Carlo Model
      for Consistency of Evidence.
AB  - Conventional genome-wide association studies (GWAS) have been proven to be a
      successful strategy for identifying genetic variants associated with complex
      human traits. However, there is still a large heritability gap between GWAS and
      transitional family studies. The "missing heritability" has been suggested to be
      due to lack of studies focused on epistasis, also called gene-gene interactions,
      because individual trials have often had insufficient sample size. Meta-analysis
      is a common method for increasing statistical power. However, sufficient detailed
      information is difficult to obtain. A previous study employed a meta-regression
      based method to detect epistasis, but it faced the challenge of inconsistent
      estimates. Here, we describe a Markov chain Monte Carlo-based method, called
      "Epistasis Test in Meta-Analysis" (ETMA), which uses genotype summary data to
      obtain consistent estimates of epistasis effects in meta-analysis. We defined a
      series of conditions to generate simulation data and tested the power and type I
      error rates in ETMA, individual data analysis and conventional meta-regression
      based method. ETMA not only successfully facilitated consistency of evidence but
      also yielded acceptable type I error and higher power than conventional meta
      regression. We applied ETMA to three real meta-analysis data sets. We found
      significant gene-gene interactions in the renin-angiotensin system and the
      polycyclic aromatic hydrocarbon metabolism pathway, with strong supporting
      evidence. In addition, glutathione S-transferase (GST) mu 1 and theta 1 were
      confirmed to exert independent effects on cancer. We concluded that the
      application of ETMA to real meta-analysis data was successful. Finally, we
      developed an R package, etma, for the detection of epistasis in meta-analysis
      [etma is available via the Comprehensive R Archive Network (CRAN) at
      https://cran.r-project.org/web/packages/etma/index.html]. 

PMID- 27045372
TI  - High-throughput dental biofilm growth analysis for multiparametric
      microenvironmental biochemical conditions using microfluidics.
AB  - Dental biofilm formation is not only a precursor to tooth decay, but also induces
      more serious systematic health problems such as cardiovascular disease and
      diabetes. Understanding the conditions promoting colonization and subsequent
      biofilm development involving complex bacteria coaggregation is particularly
      important. In this paper, we report a high-throughput microfluidic 'artificial
      teeth' device offering controls of multiple microenvironmental factors (e.g.
      nutrients, growth factors, dissolved gases, and seeded cell populations) for
      quantitative characteristics of long-term dental bacteria growth and biofilm
      development. This 'artificial teeth' device contains multiple (up to 128)
      incubation chambers to perform parallel cultivation and analyses (e.g. biofilm
      thickness, viable-dead cell ratio, and spatial distribution of multiple bacterial
      species) of bacteria samples under a matrix of different combinations of
      microenvironmental factors, further revealing possible developmental mechanisms
      of dental biofilms. Specifically, we applied the 'artificial teeth' to
      investigate the growth of two key dental bacteria, Streptococci species and
      Fusobacterium nucleatum, in the biofilm under different dissolved gas conditions
      and sucrose concentrations. Together, this high-throughput microfluidic platform
      can provide extended applications for general biofilm research, including
      screening of the biofilm properties developing under combinations of specified
      growth parameters such as seeding bacteria populations, growth medium
      compositions, medium flow rates and dissolved gas levels.

PMID- 27045373
TI  - Effects of Habitat and Social Complexity on Brain Size, Brain Asymmetry and
      Dentate Gyrus Morphology in Two Octodontid Rodents.
AB  - Navigational and social challenges due to habitat conditions and sociality are
      known to influence dentate gyrus (DG) morphology, yet the relative importance of
      these factors remains unclear. Thus, we studied three natural populations of O.
      lunatus (Los Molles) and Octodon degus (El Salitre and Rinconada), two caviomorph
      species that differ in the extent of sociality and with contrasting vegetation
      cover of habitat used. The brains and DG of male and female breeding degus with
      simultaneous information on their physical and social environments were examined.
      The extent of sociality was quantified from total group size and range area
      overlap. O. degus at El Salitre was more social than at Rinconada and than O.
      lunatus from Los Molles. The use of transects to quantify cover of vegetation
      (and other physical objects in the habitat) and measures of the spatial behavior
      of animals indicated animal navigation based on unique cues or global landmarks
      is more cognitively challenging to O. lunatus. During lactation, female O.
      lunatus had larger brains than males. Relative DG volume was similar across sexes
      and populations. The right hemisphere of male and female O. lunatus had more
      cells than the left hemisphere, with DG directional asymmetry not found in O.
      degus. Degu population differences in brain size and DG cell number seemed more
      responsive to differences in habitat than to differences in sociality. Yet, large
      sized O. degus (but not O. lunatus) that ranged over larger areas and were
      members of larger social groups had more DG cells per hemisphere. Thus, within
      population variation in DG cell number by hemisphere was consistent with a joint
      influence of habitat and sociality in O. degus at El Salitre.

PMID- 27045374
TI  - Developmental potential of clinically discarded human embryos and associated
      chromosomal analysis.
AB  - Clinically discarded human embryos, which are generated from both normal and
      abnormal fertilizations, have the potential of developing into blastocysts. A
      total of 1,649 discarded human embryos, including zygotes containing normal (2PN)
      and abnormal (0PN, 1PN, 3PN and >=4PN) pronuclei and prematurely cleaved embryos
      (2Cell), were collected for in vitro culture to investigate their developmental
      potential and chromosomal constitution using an SNP array-based chromosomal
      analysis. We found that blastocyst formation rates were 63.8% (for 2Cell
      embryos), 22.6% (2PN), 16.7% (0PN), 11.2% (3PN) and 3.6% (1PN). SNP array-based
      chromosomal analysis of the resultant blastocysts revealed that the percentages
      of normal chromosomes were 55.2% (2Cell), 60.7% (2PN), 44.4% (0PN) and 47.4%
      (0PN). Compared with clinical preimplantation genetic diagnosis (PGD) data
      generated with clinically acceptable embryos, results of the SNP array-based
      chromosome analysis on blastocysts from clinically discarded embryos showed
      similar values for the frequency of abnormal chromosome occurrence, aberrant
      signal classification and chromosomal distribution. The present study is perhaps
      the first systematic analysis of the developmental potential of clinically
      discarded embryos and provides a basis for future studies. 

PMID- 27045375
TI  - Sexual behaviour among people with HIV according to self-reported antiretroviral
      treatment and viral load status.
AB  - OBJECTIVE: To assess, among people with HIV, the association of self-reported
      antiretroviral treatment (ART) and viral load status with condomless sex with an
      HIV-serodifferent partner (CLS-D). DESIGN: Cross-sectional study of 3258 HIV
      diagnosed adults in the United Kingdom, 2011-2012. METHODS: CLS-D in the past 3
      months and self-reported ART/viral load were ascertained by questionnaire. Clinic
      recorded viral load was documented. HIV-transmission risk sex (CLS-D-HIV-risk)
      was defined as CLS-D together with either not on ART or clinic-recorded viral
      load more than 50 copies/ml. RESULTS: Of 3178 participants diagnosed more than 3
      months ago, 2746 (87.9%) were on ART, of whom self-reported viral load was '50
      copies/ml/ or less/undetectable' for 78.4%; 'more than 50 copies/ml/detectable'
      for 8.3%; 'do not know/missing' for 13.3%. CLS-D prevalence was 14.9% (326/2189),
      6.4% (23/360) and 10.7% (67/629) among men who have sex with men, heterosexual
      men and women, respectively. Among men who have sex with men, CLS-D prevalence
      was 18.8% among those not on ART; 15.2% among those on ART with undetectable self
      reported viral load; 9.8% among those on ART without undetectable self-reported
      viral load. Compared with 'on ART with undetectable self-reported viral load',
      prevalence ratios (95% confidence interval) adjusted for demographic/HIV-related
      factors were: 0.66 (0.45, 0.95) for 'on ART without undetectable self-reported
      viral load', and 1.08 (0.78, 1.49) for 'not on ART' (global P = 0.021). Among
      heterosexual men and women (combined), ART/self-reported viral load was not
      associated with CLS-D [corresponding adjusted prevalence ratios: 1.14 (0.73,
      1.79) for 'on ART without undetectable self-reported viral load'; 0.88 (0.44,
      1.77) for 'not on ART', P = 0.77]. CLS-D-HIV-risk prevalence was 3.2% among all
      participants; 16.1% for 'not on ART'; 0.6% for 'on ART with undetectable self
      reported viral load; 4.2% for 'on ART without undetectable self-reported viral
      load.' CONCLUSION: Use of ART was not associated with increased prevalence of CLS
      D, and was associated with greatly reduced prevalence of HIV-transmission risk
      sex.

PMID- 27045376
TI  - Putamen volume and its clinical and neurological correlates in primary HIV
      infection.
AB  - OBJECTIVE: Little is known about the extent of cortical and subcortical
      volumetric alterations that may occur within the first year of HIV infection
      [primary HIV infection (PHI)]. DESIGN: We used structural MRI in this prospective
      cross-sectional neuroimaging study to determine the extent of volumetric changes
      in early HIV infection. METHODS: Cerebrospinal fluid, blood, neuropsychological
      testing, and structural T1 MRI scans were acquired from 18 HIV and 47 PHI age
      matched antiretroviral-naive male participants. Using FreeSurfer 5.1, volumetric
      measurements were obtained from the caudate, amygdala, corpus callosum,
      ventricles, putamen, thalamus, cortical white matter, and total gray matter.
      Regional volumes were compared groupwise and related to biomarkers in
      cerebrospinal fluid (viral load, neopterin, and neurofilament light chain), blood
      (viral load, CD4, and CD8 T-cell count), and neuropsychometric tests (digit
      symbol, grooved pegboard, finger-tapping, and timed gait). RESULTS: A trend-level
      moderate reduction of putamen volume (P = 0.076, adjusted Cohen's d = 0.5 after
      controlling for age) was observed for PHI compared with HIV-uninfected
      individuals. Within the PHI group, putamen volume associated with CD4 cell count
      (P = 0.03), CD4/CD8 ratio (P = 0.045), infection duration (P = 0.009), and
      worsening psychomotor performance on the digit-symbol (P = 0.028), finger-tapping
      (P = 0.039), and timed gait (P = 0.009) tests. CONCLUSION: Our volumetric results
      suggest that the putamen is preferentially susceptible to early HIV-associated
      processes. Examining the natural course of early HIV infection longitudinally
      will allow for mapping of the trajectory of HIV-associated central nervous system
      changes, enabling creation of improved interventional strategies to potentially
      stabilize or reverse these observed structural changes.

PMID- 27045377
TI  - The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV
      infection.
AB  - OBJECTIVE: Following tissue barrier breaches, interleukin-33 (IL-33) is released
      as an 'alarmin' to induce inflammation. Soluble suppression of tumorigenicity 2
      (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We
      assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal
      damage in patients with early (EHI) and chronic HIV infection (CHI) and elite
      controllers. DESIGN: Analyses on patients with EHI and CHI were conducted to
      determine IL-33/sST2 changes over time. METHODS: IL-33 and sST2 levels were
      measured in plasma. Correlations between sST2 levels and plasma viral load, CD4
      and CD8 T-cell counts, expression of T-cell activation/exhaustion markers, gut
      mucosal damage, microbial translocation and inflammation markers, as well as
      kynurenine/tryptophan ratio were assessed. RESULTS: Plasma sST2 levels were
      elevated in EHI compared with untreated CHI and uninfected controls, whereas IL
      33 levels were comparable in all groups. In EHI, sST2 levels were positively
      correlated with the CD8 T-cell count and the percentage of T cells expressing
      activation and exhaustion markers, but not with viral load or CD4 T-cell count.
      Plasma sST2 levels also correlated with plasma levels of gut mucosal damage,
      microbial translocation and kynurenine/tryptophan ratio and for some markers of
      inflammation. Prospective analyses showed that early antiretroviral therapy had
      no impact on sST2 levels, whereas longer treatment duration initiated during CHI
      normalized sST2. CONCLUSION: As sST2 levels were elevated in EHI and were
      correlated with CD8 T-cell count, immune activation, and microbial translocation,
      sST2 may serve as a marker of disease progression, gut damage and may directly
      contribute to HIV pathogenesis.

PMID- 27045378
TI  - Auditory brainstem response - a valid and cost-effective screening tool for
      vestibular schwannoma?
AB  - CONCLUSION: Contemporary auditory brainstem response (ABR) is not valid as a
      screening tool for VS, when considering the sensitivity of 80%, the specificity
      of 77%, and the positive predictive value of 3.4%, MRI screening is superior to
      ABR in Denmark when considering cost-effectiveness. OBJECTIVES: The aim of this
      study is to assess the sensitivity, specificity, and cost-effectiveness of ABR vs
      MRI, when screening for VS in a clinical setting. METHOD: Data was collected on
      all patients subjected to an ABR during a 3-year period (2005-2008) at a tertiary
      referral center. The data were compared to results of MRI and with data from The
      Danish National VS Database. In total, 1447 adults underwent ABR, of whom 349
      were referred for a subsequent MRI. Sensitivity and specificity were calculated.
      To assess the cost-effectiveness of ABR vs MRI, procedure costs for ABR and MRI
      were retrieved from the National Board of Health. RESULTS: Twelve (3.4%) of 349
      patients were diagnosed with a VS. Of the 1098 patients not referred for MRI,
      three (0.3%) were later diagnosed with a VS. The sensitivity and specificity of
      ABR in diagnosing a VS were 80% and 77%, respectively. Procedure costs were 326
      EURO for the ABR and 319 EURO for the MRI.

PMID- 27045380
TI  - Human identification by FSS system adapted to cephalometric radiographs.
AB  - The aim of this study was to verify the applicability and reproducibility of the
      FSS system [8] adapted for frontal and lateral cephalometric radiographs of the
      frontal sinus for human identification purposes. Eighty lateral and frontal
      digital cephalometric radiographs from a private Dental Radiology service's
      database were evaluated. Evaluations were performed in a dimmed lighting room,
      using a 4.200 lux lightbox with mask, ultrafan paper and pencil with a 0.5
      diameter tip. The sheet of paper was superimposed on the radiograph to obtain the
      outlines of the frontal sinus and two examiners made the drawings independently
      at two different times, with a minimum period interval between evaluations. To
      obtain the linear physical measurements of the frontal sinus, a digital
      pachymeter was used. Later, all the discrete variables were codded for the
      statistical analysis. All variables were tested by means of the Cohen's Kappa
      test. The intraexaminer agreement ranged from good to perfect (p<0.001), while
      the interexaminer agreement ranged from regular to perfect (p<0.001). The use of
      frontal and lateral cephalometric radiographs was found to be reproducible and
      reliable for human identification by an adaptation of FSS system. 

PMID- 27045379
TI  - Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of
      GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.
AB  - Preventing xenograft rejection is one of the greatest challenges of
      transplantation medicine. Here, we describe a reproducible, long-term survival of
      cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which
      express human complement regulatory protein CD46 and human thrombomodulin
      (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug
      regimen includes induction with anti-thymocyte globulin and alphaCD20 antibody,
      followed by maintenance with mycophenolate mofetil and an intensively dosed
      alphaCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft
      survival in five consecutive recipients using this regimen is significantly
      prolonged over our recently established survival benchmarks (180 and 500 days,
      respectively). Remarkably, the reduction of alphaCD40 antibody dose on day 100 or
      after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In
      conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment
      regimen tested here consistently prevent humoral rejection and systemic
      coagulation pathway dysregulation, sustaining long-term cardiac xenograft
      survival beyond 900 days. 

PMID- 27045381
TI  - The influences of cultivation setting on inflorescence lipid distributions,
      concentrations, and carbon isotope ratios of Cannabis sp.
AB  - While much is known about how the growth environment influences many aspects of
      floral morphology and physiology, little is known about how the growth setting
      influences floral lipid composition. We explored variations in paraffin wax
      composition in Cannabis sp., a cash crop grown both indoors and outdoors across
      the United States today. Given an increased focus on regulation of this crop,
      there are additional incentives to certify the setting of Cannabis cultivation.
      To understand the impacts of the growth environment, we studied distributions,
      concentrations, and carbon isotope ratios of n-alkanes isolated from Cannabis sp.
      inflorescences to assess if variations within these lipid parameters were related
      to known growth settings of specimens seized by federal agents. We found that
      Cannabis plants cultivated under open-field settings had increased inflorescence
      paraffin wax abundances and greater production of lower molecular weight n
      alkanes relative to plants grown in enclosed environments. Further, the carbon
      isotope ratios of n-C29 from Cannabis plants grown in enclosed environments had
      relatively lower carbon isotope (delta(13)C) values compared to plants from open
      field environments. While this set of observations on seized plant specimens
      cannot address the particular driver behind these observations, we posit that (a)
      variations in irradiance and/or photoperiod may influence the distribution and
      concentration of inflorescence lipids, and (b) the delta(13)C value of source CO2
      and lipid concentration regulates the delta(13)C values of inflorescence n-C29
      and bulk Cannabis plant materials. Nonetheless, by using a cultivation model
      based on delta(13)C values of n-C29, the model correctly identified the growth
      environment 90% of time. We suggest that these lipid markers may be used to trace
      cultivation methods of Cannabis sp. now and become a more powerful marker in the
      future, once the mechanism(s) behind these patterns is uncovered. 

PMID- 27045382
TI  - Effects of L-cysteine on lead acetate induced neurotoxicity in albino mice.
AB  - Lead is a toxic heavy metal that adversely affects nervous tissues; it often
      occurs as an environmental pollutant. We investigated histological changes in the
      cerebral cortex, hippocampus and cerebellum of adult albino mice following
      exposure to lead acetate. We also studied the possible ameliorative effect of the
      chelating agent, L-cysteine, on lead-induced neurotoxicity. We divided albino
      mice into six groups: 1) vehicle-only control, 2) L-cysteine control, 3 and 4)
      treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, and 5 and 6)
      treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, followed by
      50 mg/kg L-cysteine for 7 days. Lead acetate administration caused
      disorganization of cell layers, neuronal loss and degeneration, and neuropil
      vacuolization. Brain sections from lead-intoxicated mice treated with L-cysteine
      showed fewer pathological changes; the neuropil showed less vacuolization and the
      neurons appeared less damaged. L-cysteine at the dose we used only marginally
      alleviated lead-induced toxicity. 

PMID- 27045383
TI  - Deep sequencing of hepatitis C virus reveals genetic compartmentalization in
      cerebrospinal fluid from cognitively impaired patients.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) causes neuropsychiatric impairment and
      fatigue with recent studies suggesting HCV invasion of the central nervous system
      (CNS). Our previous finding that endothelial cells from the blood-brain barrier
      support HCV infection warrants further investigation to elucidate whether the CNS
      can serve as a reservoir for independent HCV evolution. METHODS: Cerebrospinal
      fluid (CSF) and plasma from six HCV-infected patients without liver disease or co
      morbidities together with plasma from six healthy subjects were profiled for
      markers of immune activation and viral quasispecies measured by deep sequencing.
      Unsupervised data analyses were used to identify any associations between
      cytokine activation markers and clinical outcomes. RESULTS: Four of six HCV
      infected patients showed significant evidence of cognitive dysfunction and
      fatigue. Deep sequencing revealed independent viral evolution within the CNS of
      two cognitively impaired patients. Principal component analysis of peripheral
      cytokines demonstrated that individuals without cognitive impairment clustered
      together while a distinct cytokine pattern emerged with patients exhibiting
      cognitive dysfunction and fatigue. CONCLUSIONS: Deep sequencing demonstrated
      unique viral variants in the CSF of two cognitively impaired patients consistent
      with CNS replication or sequestration. Meanwhile, compartmentalization was absent
      in infected patients with no neurocognitive impairment. Examination of cytokine
      profiles in HCV-infected patients with cognitive dysfunction revealed elevated
      peripheral cytokine levels resulting in a distinct cytokine profile that may be
      related to cognitive impairment or viral penetration into the CNS. Further
      studies to determine the significance of unique HCV variants within the CNS are
      warranted.

PMID- 27045384
TI  - An Econometric Model of Healthcare Demand With Nonlinear Pricing.
AB  - From 2004 to 2012, the German social health insurance levied a co-payment for the
      first doctor visit in a calendar quarter. We develop a new model for estimating
      the effect of such a co-payment on the individual number of visits per quarter.
      The model combines a one-time increase in the otherwise constant hazard rate
      determining the timing of doctor visits with a difference-in-differences strategy
      to identify the reform effect. An extended version of the model accounts for a
      mismatch between reporting period and calendar quarter. Using data from the
      German Socio-Economic Panel, we do not find an effect of the co-payment on demand
      for doctor visits. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27045385
TI  - Skeletal Muscle Function in Young Patients With Cystic Fibrosis.
AB  - PURPOSE: Defects in the gene encoding the cystic fibrosis (CF) transmembrane
      conductance regulator (CFTR) cause CF. Absence of the CFTR may result in skeletal
      muscle dysfunction. Here, we tested skeletal muscle function in male adolescent
      patients with CF. METHODS: Ten CF and 10 control participants (age: 16.8 +/- 0.6
      years) performed 7 repetitive sets of maximum voluntary contractions (MVCs) and
      underwent an isometric fatigue test of the knee extensors. Electromyography (EMG)
      activity was recorded from the m. vastus lateralis (VL) and m. vastus medialis
      (VM). RESULTS: In CF, the MVC torque was lower and correlated with the predicted
      forced expiratory volume in one second (r = .73, p = .012, n = 10). The M-wave in
      the VL was shorter in CF than in controls (18.6 +/- 0.5 vs. 20.3 +/- 0.5 ms, p <
      .028). In the VM, both the M-wave (4.96 +/- 0.61 vs. 7.97 +/- 0.60 mV, p = .001)
      and the EMG (0.29 +/- 0.04 vs. 0.47 +/- 0.04 mV, p = .004) amplitudes were
      smaller in CF. CONCLUSION: The differences in the VL and VM EMG signals between
      the groups indicate that the lower MVC torque in CF did not result from the
      direct impact of a CFTR defect on the sarcolemmal excitability; the differences
      more likely resulted from the less developed musculature in the patients with CF.

PMID- 27045386
TI  - Insight into the pharmacokinetic behavior of tanshinone IIA in the treatment of
      Crohn's disease: comparative data for tanshinone IIA and its two glucuronidated
      metabolites in normal and recurrent colitis models after oral administration.
AB  - 1. Previous reports implied that tanshinone IIA (TSA) may offer potential
      benefits for Crohn's disease (CD). However, the detailed pharmacokinetic behavior
      of TSA in the treatment of colitis remain unclear. Herein, a recurrent
      trinitrobenzene sulfonic acid (TNBS)-colitis mouse model was used to investigate
      whether TSA possesses favorable pharmacokinetic and colonic distribution profiles
      to serve as a candidate drug. 2. Although the systemic TSA exposures were low
      (AUC0-t approximately 330 ng*h/ml) in both the normal and colitis models after
      oral administration TSA 20 mg/kg, high levels of TSA were found in the
      gastrointestinal tract (GI). Such a GI exposure of TSA in colitis mice is
      adequate to exert anti-inflammatory effects as observed in various in vitro
      studies. 3. Interestingly, colonic TSA exposure in the colitis mouse model was
      much lower than that in the normal mice, which may be explained by a significant
      upregulation of colonic UDP-glucuronosyltransferase (Ugt)1a9 expression and a
      higher plasma concentration of TSA glucuronides in the model mice at 0.5, 1 and 2
      h after TSA administration. 4. Together, these results reveal high accumulation
      at the site of inflammation and minimal systemic concentration of TSA, which are
      favorable pharmacokinetic behaviors to meet the requirements for CD treatment.

PMID- 27045387
TI  - Blood removal therapy in hereditary hemochromatosis induces a stress response
      resulting in improved genome integrity.
AB  - BACKGROUND: Hereditary hemochromatosis (HH) is a common disease of iron
      metabolism, manifesting with iron overload and affecting up to 1% of individuals
      of northern European descent. Untreated HH can result in irreversible damage of
      the liver and pancreas, potentially leading to cancer and diabetes. Therapy
      consists of normalizing iron stores by repeated blood donations (phlebotomy).
      Treated HH patients have normal survival rates and report less tiredness after
      phlebotomy; however, it is not understood why musculoskeletal symptoms may
      persist in spite of iron removal. We hypothesize that phlebotomy therapy does not
      simply reverse iron accumulation but has additional effects at the subcellular
      level. In particular, the systemic impact of phlebotomy on mitochondria and
      genome integrity is largely unknown. STUDY DESIGN AND METHODS: The effects of
      phlebotomy therapy on mitochondrial iron proteins and genome integrity were
      investigated in peripheral blood mononuclear blood cells from HH patients.
      RESULTS: After the reduction of systemic iron load in these patients with
      phlebotomy, we observed increased expression of mitochondrial superoxide
      dismutase, reduced iron sulfur assembly protein (Iscu1/2), and improved genome
      integrity. CONCLUSION: We conclude that phlebotomy therapy in HH does not merely
      restore systemic iron homeostasis, but induces an "oxidative stress" defense
      response that manifests as improved genome integrity. These findings provide
      novel insights into an ancient therapy.

PMID- 27045388
TI  - Transcriptional transactivator peptide modified lidocaine-loaded nanoparticulate
      drug delivery system for topical anesthetic therapy.
AB  - PURPOSE: For the topical anesthetic, transcriptional transactivator peptide (TAT)
      modified lidocaine (LID) loaded nanostructured lipid carriers (TAT-NLCs-LID) were
      prepared and then used for improving transdermal delivery of local anesthetic
      drug. METHODS: In this study, TAT was conjugated with Distearoyl
      phosphatidylethanolamine-(polyethylene glycol)2000-maleimide (DSPE-PEG2000-Mal)
      to obtain TAT-PEG2000-DSPE. TAT-NLCs-LID were successfully prepared and
      characterized by determination of their particle size, morphology, drug
      encapsulation efficiency and in vitro drug release behavior. The skin permeation
      of LID-LNPs was examined using a Franz diffusion cell mounted with depilated
      mouse skin in vitro and in vivo anesthesia effect was evaluated on mice. RESULTS:
      The results showed that TAT-NLCs-LID have substantially small mean diameter
      (157.9 nm) and high encapsulation efficiency (81.8%). From the in vitro skin
      permeation results, transdermal flux of TAT-NLCs-LID was about several times
      higher than that of LID solution and NLCs-LID. In vivo anesthesia effect
      evaluation illustrated that TAT-NLCs-LID can enhance the transdermal delivery of
      LID by reducing the pain threshold in mice. CONCLUSION: These results indicate
      that the novel TAT containing drug delivery system is very useful for overcoming
      the barrier function of the skin and could deliver anesthetic through the skin.
      TAT-NLCs-LID could function as promising topical anesthetic system.

PMID- 27045389
TI  - Bipolar Disorder Type 1 in a 17-Year-Old Girl with Wolfram Syndrome.
AB  - OBJECTIVE: Wolfram syndrome (WS, MIM 222300) is a rare autosomal, recessive
      neurodegenerative disorder associated with mutations in WFS1, a gene that has
      been associated with bipolar disorder (BD). WS, characterized by the association
      of juvenile-onset diabetes mellitus (DM) and bilateral progressive optic atrophy
      (BPOA), encompasses several other clinical features, including cognitive
      impairments and psychiatric disorders. Detailed data on the psychiatric phenotype
      are still scarce, and how WS relates to BD is still unknown. METHOD: A 17-year
      old girl with WS was hospitalized for early-onset BD. A multidisciplinary and
      developmental assessment was carried out to control mood symptoms and address how
      BD could be related to WS. RESULTS: Besides DM and BPOA, the patient had several
      risk factors for BD/mood disorders as follows: (1) a history of abuse and
      maltreatment; (2) a history of specific language disorder and borderline
      intelligence associated with academic failure; and (3) a comorbid hypothyroidism.
      Treatment encompassed all aspects of the adolescent's conditions, such as the use
      of mood stabilizers, addressing psychosocial and scholastic problems, and
      treating hypothyroid dysfunction. CONCLUSION: Given the complexity of WS, this
      case suggests that the possible association between WS and BD should not only be
      merely limited to a possible statistical association with WFS1 polymorphism but
      also to developmental, cognitive, and endocrine risk factors for BD.

PMID- 27045390
TI  - To Polarize or Not to Polarize? Charge-on-Spring versus KBFF Models for Water and
      Methanol Bulk and Vapor-Liquid Interfacial Mixtures.
AB  - Simulations of water and methanol mixtures using polarizable force fields (FFs)
      for methanol (COS/M and CPC) and water (COS/G2) were performed and compared to
      experiment and also to a nonpolarizable methanol (KBFF) model with SPC/E water in
      an effort to quantify the importance of explicit electronic polarization effects
      in bulk liquid mixtures and vapor-liquid interfaces. The bulk liquid mixture
      properties studied included the center of mass radial distribution functions,
      Kirkwood-Buff integrals (KBIs), volumetric properties, isothermal
      compressibility, enthalpy of mixing, dielectric constant, and diffusion
      coefficients. The vapor-liquid interface properties investigated included the
      relative surface probability distributions, surface tension, excess surface
      adsorption, preferred surface molecule orientations, and the surface dipole. None
      of the three FFs tested here was clearly superior for all of the properties
      examined. All the force fields typically reproduced the correct trends with
      composition for both the bulk and interfacial system properties; the differences
      between the force fields were primarily quantitative. The overall results suggest
      that the polarizable FFs are not, at the present stage of development, inherently
      better able to reproduce the studied bulk and interfacial properties-despite the
      added degree of explicit transferability that is, by definition, built into the
      polarizable models. Indeed, the specific parametrization of the FF appears to be
      just as important as the class of FF. 

PMID- 27045391
TI  - Evaluation of Patient Safety Indicators in Semnan City Hospitals by Using the
      Patient Safety Friendly Hospital Initiative (PSFHI).
AB  - BACKGROUND: Nowadays, patient safety issue is among one of the main concerns of
      the hospital policy worldwide. This study aimed to evaluate the patient safety
      status in hospitals affiliated to Semnan city, using the WHO model for Patient
      Safety Friendly Hospital Initiatives (PSFHI) in summer 2014. METHODS: That was a
      cross sectional descriptive study that addressed patient safety , which explained
      the current status of safety in the Semnan hospitals using by instrument of
      Patient safety friendly initiative standards (PSFHI). Data was collected from 5
      hospitals in Semnan city during four weeks in May 2014. RESULTS: The finding of 5
      areas examined showed that some components in critical standards had
      disadvantages. Critical standards of hospitals including areas of leadership and
      administration, patient and public involvement and safe evidence-based clinical
      practice, safe environment with and lifetime education in a safe and secure
      environment were analyzed. The domain of patient and public involvement obtained
      the lowest mean score and the domain of safe environment obtained the highest
      mean score in the surveyed hospitals. CONCLUSION: All the surveyed hospitals had
      a poor condition regarding standards based on patient safety. Further, the
      identified weak points are almost the same in the hospitals. Therefore, In order
      to achieve a good level of all aspects of the protocol, the goals should be
      considered in the level of strategic planning at hospitals. An effective
      execution of patient safety creatively may depend on the legal infrastructure and
      enforcement of standards by hospital management, organizational liability to
      expectation of patients, safety culture in hospitals.

PMID- 27045392
TI  - Safety & Efficacy of Cyclic Zoledronic Acid Therapy on Pediatric Secondary
      Osteoporosis.
AB  - BACKGROUND/AIM: Osteoporosis is a systemic disease characterized by decreased
      bone density and increased tendency to develop fractures. Osteoporosis in
      children and adolescents is a rare disease usually secondary to Medical
      conditions or medications given to children. The condition affects normal bone
      growth and development and carries with it multiple morbidities (physical and
      psychological) if not corrected promptly. This study aims to share our experience
      with Zoledronic Acid Therapy in Pediatric patients with secondary osteoporosis.
      METHOD: A retrospective study which included 46 patients aged 3 to 18 years. All
      patients received specific doses of Zoledronic acid and were followed up at King
      Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Clinical and
      laboratory data were collected for each patient from their files. Adverse events
      were also recorded. RESULTS: The use of Zoledronic Acid in children and
      adolescents appears to be statically significant reduce fracture rate (p=0.005),
      bone turnover markers (Osteocalcin p= 0.003, CTX p= 0.008) and pain frequency in
      symptomatic individuals (p=0.000). Careful selection of cases is required to
      provide maximum benefits compared to risks associated with therapy. CONCLUSION:
      This study demonstrates that Zoledronic acid has positive effects on clinical
      outcome and bone marker level as well as quality of life for Pediatric patients
      with Osteoporosis and their families, with no long-term side effects.

PMID- 27045393
TI  - Cognitive Vulnerability in Patients with Generalized Anxiety Disorder, Dysthymic
      Disorder and Normal Individuals.
AB  - AIM: The purpose of this study was to assess cognitive vulnerability and response
      style in clinical and normal individuals. METHOD: A sample of 90 individuals was
      selected for each of the 3 groups of Generalized Anxiety disorder, Dysthymic
      disorder and normal individuals. They completed MCQ and RSQ. RESULTS: Results
      analyzed by MANOVA and post hoc showed significant differences among groups.
      Dysthymic group and GAD reported higher scores on cognitive confidence compared
      to the normal group. Individuals with GAD showed highly negative beliefs about
      need to control thought, compared to the other groups, but in cognitive self
      consciousness they have no differences with the normal group. In regard to
      uncontrollability, danger and positive beliefs, GAD group had higher levels than
      the other groups. Although normal and GAD group didn't show any significant
      differences in response style, there was a significant difference between
      Dysthymic group and other groups in all response styles. DISCUSSION:  Beliefs and
      meta-cognitive strategies can be distinguished between clinical and non clinical
      individuals. Also, findings support the Self-Regulatory Executive Function model.
      ary committee was effective in recognizing, designing and implementing tailored
      interventions for reduction of medication errors. A systematic approach is
      urgently needed to decrease organizational susceptibility to errors, through
      providing required resources to monitor, analyze and implement effective
      interventions.

PMID- 27045394
TI  - Altruism the Essense of the Iranian Nurses' Job Satisfaction: A Qualitative
      Study.
AB  - Skillful and efficient human resource is one of the most important tools for
      reaching the organizational targets and it is almost impossible to reach the
      predetermined goals and success without having skillful human resources.
      Therefore, having a study on the personnel's job satisfaction is recommended for
      all of the organizations. Since the health organizations are among the most
      important organizations of any country, paying attention to the nurses' job
      satisfaction as the main providers of the health care services gets very
      important. In fact, their attempts guarantee the efficient human resources'
      health in the society. Understanding the Iranian nurses' experiences of their job
      satisfaction. The present paper studies the implicit and explicit aspects of the
      clinical nurses' job satisfaction. The needed information is collected via
      interviews, and then the participants' contextual data is analyzed by the
      qualitative content analysis. The research results introduce the altruism as the
      foundation for the nurses' job satisfaction. Altruism is composed of three
      categories of the patient advocacy, spiritual job satisfaction, and professional
      commitment. Altruism has made the nurses deliver the required health cares to the
      patients with all their love, while their profession has many difficulties. Job
      satisfaction resulted from altruism is experienced as a pleasant feeling along
      with enjoyment resulted from addressing the needs of a patient who looks forward
      to the nurse's advocacy. According to this kind of job satisfaction, the nurse's
      professional commitment is to advocate for the patient. Also, the research
      results show that spirituality is the inseparable component of altruism and it
      has a vital role in the nurses' job satisfaction. The spirituality helps the
      nurses to deliver targeted acts and interventions. 

PMID- 27045395
TI  - Development of Children in Iran: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: In order to gain a better perspective of the developmental status of
      children in different regions of Iran, this study was carried out to determine
      the prevalence and the factors impacting child development in Iranian studies.
      MATERIALS & METHODS: Articles published in Iranian and international journals
      indexed in the SID, PubMed, Scopus and Magiran databases from 2001-2015 were
      systematically reviewed using standard and sensitive keywords. After evaluating
      the quality of 155 articles in the initial search, 26 articles were analyzed
      according to the inclusion criteria. After investigations, meta-analysis was done
      for six studies and the results were combined using Random Effects model, and the
      heterogeneity of studies was evaluated using the I2 index. Data analysis was
      performed using STATA version 11.2. RESULTS: Eagger & Beggs tests, respectively
      with 0/273 & 0/260 did not confirm the probability of publication bias in the
      data, but heterogeneity in studies was confirmed (p?0/001). On such basis, the
      pooled prevalence of developmental disorder based on Random Effect model was
      calculated to be 0.146, CI (0/107-0/184). The prevalence of developmental
      disorders in children in the studies reviewed was reported between 7 to 22.4%.
      The most important risk factors were in SES )Socio Economic Status) and Prenatal,
      Perinatal, Neonatal &Child groups. CONCLUSION: More extensive studies and early
      intervention with respect to causes of developmental delay in children seems
      necessary.

PMID- 27045396
TI  - Fruit and Vegetable Consumption among Special School Students with Mild
      Intellectual Disability in Hong Kong.
AB  - OBJECTIVE: The aim of this study was to predict the fruit and vegetable
      consumption intention of students with mild intellectual disability in Hong Kong
      by the application of Ajzen's Theory of Planned Behaviour. METHODS: 50 students
      with mild intellectual disability (30 male and 20 female), ranging in age from 15
      to 38 years, were participated in this study. By means of face-to-face
      interviews, demographic data, Food Preference and variables of Theory of Planned
      Behaviour, such as Attitude, Subjective Norm and Perceived Behavioural Control
      were measured. RESULTS: 20%, 28% and 10% students with mild intellectual
      disability were rated to be overweight, obese and severely obese respectively.
      The rest of 10% were classified to be underweight. Regarding the daily intake of
      fruit and vegetable, 96% students with mild intellectual disability failed to
      consume sufficient amount. The variables of Theory of Planned Behaviour explained
      47.7% of fruit and vegetable consumption intention with significant factors of
      Attitude, Subjective Norm and Perceived Behavioural Control. Food Preference was
      found to be a useful construct and further improve the prediction by about 7%
      after incorporating into the model. CONCLUSIONS: Results of this study indicated
      that Theory of Planned Behaviour is a useful model to predict dietary intention
      of students with mild intellectual disability in Hong Kong. Food Preference was a
      significant predictor to model the intention of fruit and vegetable consumption
      among students other than Attitude, Subjective Norm and Perceived Behavioural
      Control.

PMID- 27045397
TI  - Life Satisfaction Index among Elderly People Residing in Gorgan and Its
      Correlation with Certain Demographic Factors in 2013.
AB  - BACKGROUND: Aging is a universal phenomenon that will present itself as a
      dominant social and welfare challenge. AIM: This study was to examine life
      satisfaction among people residing in Gorgan and its correlation with certain
      demographic factors in 2013. METHODS: A total of 250 elder people were selected
      for the study through the convenience sampling during 4 months. Data collected
      through life satisfaction index-A (LSIA). This instrument consists of 5
      subscales, including, zest for life, resolution and fortitude, congruence between
      desired and achieved goals, positive self-concept and mood tone. The Multiple
      Linear Regression analysis was used in order to determine factors influencing the
      overall LSIA. RESULTS: The overall LSIA score was 22.1 +/- 7.5 with the maximum
      and minimum mean scores pertaining to the resolution and fortitude (6.1 +/- 2.5)
      and the positive self-concept (3.1 +/- 1.2) subscales, respectively. Level of
      education, type of living and gender were variables influencing the overall LSIA
      (P<0.05). CONCLUSION: Given the overall LSIA, it appears that future plans for
      this age group should be seriously revised along with cultural plans for
      promoting reverence for old age in the general public.

PMID- 27045398
TI  - Knowledge, Attitude, and Performance of Nurses toward Hand Hygiene in Hospitals.
AB  - INTRODUCTION: The proper hand hygiene is one of the foremost techniques to reduce
      Nosocomial infections. The hand hygiene is deemed as the simplest method for
      control of Nosocomial infections if it is done properly it may prevent from a lot
      of costs and fatalities. Due to constant relationship with patients, nurses play
      paramount role in proper execution of hand hygiene among clinical personnel. The
      current study was carried out in order to analyze knowledge, attitude, and
      performance of nurses regarding hand hygiene. MATERIALS & METHODOLOGY: A cross
      sectional study was conducted on 200 (of 240) nurses from three hospitals in
      Kerman city at east of Iran in 2015. The standardized questionnaire was the tool
      for data collection. These data entered in SPSS (V.22). The frequency and
      percentage of frequency in descriptive statistics was employed for data analysis.
      The confidence interval was considered as 95%. RESULTS: The results showed that
      the majority of participants were male173 (86.5%), had BA degree 161 (80.5%) and
      were married 155 (70.5%). Most of nurses 77 (38.5%) had working experience (5
      10years). The majority of nurses had good knowledge 149 (74.5%), positive
      attitude 141 (70.5%) and good performance 175 (87.5%). DISCUSSION & CONCLUSION:
      The nurses are good level in terms of knowledge, attitude, and performance but
      improvement of their knowledge and knowledge seems to be more necessary by
      holding educational classes and courses in cases where they have less knowledge.

PMID- 27045399
TI  - Status of Hearing Loss and Its Related Factors among Drivers in Zahedan, South
      Eastern Iran.
AB  - OBJECTIVE: This study aims to investigate loss of hearing among drivers in
      Zahedan, southeastern Iran. PATIENTS & METHODS: This study carried out on a total
      of 1836 drivers in Zahedan in 2013. Loss of hearing in both ears was measured at
      250, 1000, 2000, 3000, 4000, 6000, and 8000 Hertz. The demographic variables,
      blood parameter and anthropometric data were recorded through interview and
      examinations. Data were analyzed in Stata.12 software using paired t-tests,
      McNemar test and Multiple Logistic Regression. RESULTS: The mean age was 38.2+/
      9.8 years. The highest mean hearing thresholds in the right and left ears were
      25.7+/-9.1 and 27.7+/-9.1, respectively at 250 Hz. There was significant
      difference between left and right ears hearing threshold at all frequencies
      (P<0.001), and the highest difference occurred at 250 Hz. Hearing threshold in
      the left ear was greater than in the right ear at all frequencies. Hearing
      threshold was correlated to marital status, type of license, and vehicle,
      smoking, age, and driving history at all frequencies (P<0.01), and also
      significantly correlated to blood sugar and cholesterol levels at 250 and 500 Hz
      in both left and right ears (P<0.01). CONCLUSION: In conclusion, high levels of
      noise increase hearing threshold with greatest damage to the left ear. Therefore,
      drivers should be periodically examined for ear damage in accordance to variables
      affecting loss of hearing. Moreover, drivers must be educated about usage of
      appropriate ear-plugs during driving, especially for the left ear.

PMID- 27045400
TI  - A Review of Marital Intimacy-Enhancing Interventions among Married Individuals.
AB  - BACKGROUND: Lack of intimacy is currently the main concern rather than main
      concern of the experts in psychology and counseling. It is considered as one of
      the most important causes for divorce and as such to improve marital intimacy a
      great number of interventions have been proposed in the literature. Intimacy
      training and counseling make the couples take effective and successful steps to
      increase marital intimacy. No study has reviewed the interventions promoting
      marital intimacy after marriage. Thus, this review study aimed to classify the
      articles investigating the impact of interventional programs on marital intimacy
      after marriage. SEARCH METHODS: In April 2015, we performed a general search in
      Google Scholar search engines, and then we did an advanced search the databases
      of Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, Cochrane
      Library, and Psych info; Cumulative Index to Nursing and Allied Health Literature
      (CINAHL). Also, lists of the references of the relevant articles were reviewed
      for additional citations. Using Medical Subject Headings (MESH) keywords:
      Intervention (Clinical Trials, Non-Randomized Controlled Trials, Randomized
      Controlled Trials, Education), intimacy, marital (Marriage) and selected related
      articles to the study objective were from 1995 to April 2015. Clinical trials
      that evaluated one or more behavioral interventions to improve marital intimacy
      were reviewed in the study. MAIN RESULTS: 39 trials met the inclusion criteria.
      Eleven interventions had follow-up, and 28 interventions lacked follow-up. The
      quality evidence for 22 interventions was low, for 15 interventions moderate, and
      for one intervention was considered high. Findings from studies were categorized
      in 11 categories as the intimacy promoting interventions in dimensions of
      emotional, psychological, physical, sexual, temporal, communicational, social and
      recreational, aesthetic, spiritual, intellectual intimacy, and total intimacy.
      AUTHORS' CONCLUSIONS: Improving and promoting communication, problem solving,
      self-disclosure and empathic response skills and sexual education and counseling
      in the form of cognitive-behavioral techniques and based on religious and
      cultural context of each society, an effective step can be taken to enhance
      marital intimacy and strengthen family bonds and stability. Health care providers
      should consider which interventions are appropriate to the couple characteristics
      and their relationships.

PMID- 27045401
TI  - An Analysis of the Structural Factors Affecting the Public Participation in
      Health Promotion.
AB  - The present study focuses on analyzing national and international Community-Based
      Participatory Research (CBPR) studies published from 2000 to 2010 in order to
      identify and categorize the possible factors that affect social participation for
      improving the public health. Clearly, improving the public health necessitates a
      combination of the participation and responsibility by the social members and the
      attempts by public health policy-makers and planners. CBPR studies are selected
      as the corpus since they seek to encourage active and informed participation of
      the social members in fulfilling the health related goals. The present study is
      conducted through meta-synthesis within a qualitative framework. The results
      revealed a set of factors within the structural capacities which were employed by
      the CBPR researchers for achieving the health promotion goals. The structural
      capacities employed in the interventions could be considered on the cultural and
      social grounds. The cultural grounds were divided into scientific and religious
      attempts. For the scientific attempts, the results highlighted the participation
      of higher education institutes including universities and research centers as
      well as educational institutes such as schools and the relevant institutions. And
      regarding the religious attempts, the results indicated that the cooptation of
      religious centers played the greatest role in enhancing the public participation.

PMID- 27045402
TI  - BCL-1 Gene Rearrangements in Iranian Non-Hodgkin Lymphoma Patients.
AB  - In the present study, our aim was to assess the incidence of BCL-1 gene
      rearrangements in formalin-fixed paraffin embedded (FFPE) tissue in patients with
      non-Hodgkin lymphomas (NHL). The BIOMED-2 protocol was applied to assess the BCL
      1 gene rearrangements in NHL patients. PCR amplification was carried out on FFPE
      in 100 patients with B-cell lymphoma including 89 cases with diffused large B
      cell lymphoma (DLBCL) (15 cases under 18 years old) and 11 cases with mantle cell
      lymphoma (MCL). Out of the 100 patients, 19 cases (19%) were identified to have
      concurrent translocation involving BCL-1. The significant association was seen
      between BCL-1 gene rearrangements and the lymphomas in patients older than 55
      years (P<0.05). Out of 100 cases, 80 cases were positive and 20 cases were
      negative regarding CD20. No significant association was found between DLBCL
      lymphoma in patients under 18 years old and BCL-1 gene rearrangements (P>0.05).
      In addition, the positive and negative expressions of LCA/CD45 marker were 76%
      (76/100) and 26% (26/100), respectively. Our findings revealed that BCL-1 gene
      rearrangement assays using BIOMED-2 protocol can be considered as a valuable
      approach in detection of the lymphomas. 

PMID- 27045403
TI  - Sleep Hygiene Pattern and Behaviors and Related Factors among General Population
      in West Of Iran.
AB  - INTRODUCTION: Sleep hygiene was found as an important predictor for sleep
      quality. People's sleep hygiene can have a major role in their daily function.
      The purpose of the study was to determine sleep hygiene patterns and sleep
      hygiene behaviors and factors affecting them in the general population of
      Kermanshah, Iran. MATERIAL & METHODS: In this cross-sectional study, 1829 men and
      1262 women were selected randomly from 50 clusters of different parts of the
      city. The inclusion criteria were age between 12 and 65 years and living in
      Kermanshah. The exclusion criteria were psychiatric disorder and known general
      medical conditions that affecting sleep. The data collection instruments were
      demographic questionnaire and Sleep Hygiene Questionnaire, consisted of 13 items
      about biological rhythm and bed room environment and behaviors that affecting
      sleep. Data were analyzed by using SPSS version 16 software. RESULTS: The highest
      percentage was obtained for irregular woke and went up from day to day or at
      weekend and holidays (74.8%). Only 213 (6.9%) participants were classified as
      having good sleep hygiene (score 12-14). The mean age of very poor, poor,
      moderate, and good sleepers was 34.8 +/- 14.4, 33.7 +/- 17.4, 36.5 +/- 13.8, and
      35 +/- 13.7years, respectively. There were significant differences between the
      age of poor and moderate sleepers and also sleep hygiene patterns with respect to
      sex, education level and job. CONCLUSION: Poor sleep hygiene were more frequent
      in Iranian peoples and the major problem in sleep hygiene in our study was
      inappropriate sleep schedule.

PMID- 27045404
TI  - Sleep Quality and Depression and Their Association with Other Factors in
      Hemodialysis Patients.
AB  - BACKGROUND: Sleep disorders and depression, accompanied by reduced quality of
      life and increased mortality are the most common psychological problems in
      dialysis patients. This study was conducted with the aim to investigate
      depression and sleep quality and their association with some demographic and
      clinical factors in hemodialysis patients. METHOD: This descriptive-correlative
      study was conducted on 310 patients undergoing hemodialysis in 8 centers in
      educational hospitals in Mazandaran University of Medical Sciences. Data
      collection tools included a demographic questionnaire, Beck Depression Inventory,
      and Pittsburg Sleep Quality Index (PSQI). Statistical analysis was conducted
      using Chi-Square test and regression model. RESULTS: Results obtained showed
      44.8% depression in patients. Significant relationships were found between
      depression and increased blood phosphorus (P=0.002) and urea (P=0.001). Poor
      sleep quality was observed in 73.5% of hemodialysis patients, which was found
      significantly related to aging (P=0.048), female (P=0.04), and reduced frequency
      of weekly hemodialysis (P=0.035). CONCLUSION: Depression and poor sleep quality
      are two common factors in hemodialysis patients, but patients do not overtly show
      symptoms of these disorders.

PMID- 27045405
TI  - Health Promoting Lifestyle Behaviors in Menopausal Women: A Cross-Sectional
      Study.
AB  - BACKGROUND: Determining health promoting lifestyle behaviors of age-specific
      groups of women provides valuable information for designing health promotion
      intervention programs. Hence the present study was conducted to assess health
      promoting lifestyle behaviors in menopausal women. METHODS: The present
      descriptive cross-sectional study examined health promoting lifestyle behaviors
      in 400 menopausal women admitted to health care centers in Neka city-north of
      Iran-from March 2015 to July 2015. Health promoting lifestyle behaviors were
      evaluated using a demographic characteristics form and the Health Promoting
      Lifestyle Profile II (HPLP II) through simple convenience sampling. Data were
      analyzed in SPSS version 18 using descriptive and inferential statistics at the
      significance level of P<0.05. RESULTS: The mean score of participants' health
      promoting lifestyle behaviors was 136.43+/-19.61, ranging from 88 to 194. The
      logistic regression test revealed women's health promoting lifestyle behaviors to
      be significantly related to their place of residence (P=0.009, odds ratio=1.73)
      and their spouse's level of education (P=0.027, odds ratio=0.58). The Pearson
      correlation test showed significant relationships between mean score of the six
      sub-scale of health promoting lifestyle behaviors with each other (P<0.001).
      CONCLUSION: These findings have implications for addressing the role of men to
      promote health promoting lifestyle behaviors among rural menopausal women.

PMID- 27045406
TI  - Primary Dysmenorrhea and Menstrual Symptoms in Indian Female Students:
      Prevalence, Impact and Management.
AB  - BACKGROUND: Dysmenorrhea is the most common gynecological problem among females
      and it is defined as cramping pain in the lower abdomen occurring just before or
      during menstruation. Menstrual symptoms are a broad collection of affective and
      somatic concerns that occur around the time of menses. The effect and importance
      of dysmenorrhea is very wide, therefore managing the problem is important.
      OBJECTIVE: To ascertain the prevalence, and impact of primary dysmenorrhea in
      student girls and their management behaviors. METHODS & MATERIALS: A Cross
      sectional study was conducted on 1000 healthy females aged 11-28 years.
      Standardized Self-reporting questionnaires were used to obtain relevant data.
      Pain intensity was assessed by using the Numerical Pain Scale (NPS). Data was
      analyzed by SPSS version 16. RESULTS: Prevalence of dysmenorrhea was 70.2%.
      Majority of the subjects experienced pain for one or 1-2 days during
      menstruation. 23.2% of the dysmenorrheic girls experienced pain for 2-3 days. The
      most common symptom in both dysmenorrheic and non dysmenorrheic girls during the
      menstrual periods was tiredness and second most prevalent symptom was back
      pain.Females experiencing mild pain on an average absented for one and half day a
      month while 2.1+/-1.2 and 2.5+/-1.3 days for those who experienced moderate and
      severe forms of dysmenorrhea respectively. A small proportion of girls sought
      pharmacological management (25.5%) and 83.2% depended on non-pharmacological
      methods. Only 14.2% had sought medical advice. CONCLUSION: Sub optimal use of the
      medical advice and the barriers to seek medical attention by dysmenorrheic
      females need exploration. It is important that health education on puberty and
      menstruation is regarded as inadequate for many girls in India.

PMID- 27045407
TI  - The Effect of Loneliness on Social Networking Sites Use and Its Related
      Behaviors.
AB  - INTRODUCTION: The current research was conducted to examine the effect of
      "Loneliness", on time spent in Social Networking Sites (S.N.S), main reasons for
      S.N.S use, and its related behaviors. MATERIALS & METHODS: 156 students of Shiraz
      University voluntarily participated in this research. Loneliness was assessed
      usingthe UCLA Loneliness scale. 25% of highest scoring students reported that
      they were lonely whereas 25% of the lowest scoring students were considered to be
      non-lonely. The positive and negative reasons of using S.N.S were assessed based
      on Reasons for Internet Use Scale, and internet behaviors were assessed based on
      Scale of Internet Behaviors. RESULTS: There was no difference in time spent in
      S.N.S as well as the positive and negative reasons of using S.N.S (contrary to
      literature), but internet behaviors showed a significant difference between
      "lonely" and "non-lonely" individuals. "Lonely" and "non-lonely" individuals
      showed a significant difference in "social aspect" of S.N.S behaviors. There was
      also a significant difference between "Lonely" and "non-Lonely" individuals in
      "Negative impact" of S.N.S behaviors. Yet, there seemed to be no difference in
      "competency and convenience aspect" of S.N.S behaviors. CONCLUSIONS: This study
      suggested that there is no difference between lonely and non-lonely individuals
      in reasons for using S.N.S and time spent in S.N.S. This finding stands contrary
      to previous research findings and general literature on the subject In other
      words, what drives people to S.N.S at the first place shows no significant
      difference between lonely and non-lonely individuals while after attending S.N.S,
      social behavior of lonely individuals shows a significant difference which is
      consistently enhanced online. Lonely people also significantly develop internet
      related problems in their daily functioning, including interference with real
      life socializing.

PMID- 27045408
TI  - Relation between Lifestyle and Socio-Demographic Factors and Body Composition
      among the Elderly.
AB  - BACKGROUND: Aging is accompanied by various changes that can cause changes in
      diet and body composition resulting sometimes in malnutrition and disability in
      the elderly. Changes in body composition among the elderly are mainly the result
      of physical inactivity and nutrition. This study was designed to examine the
      relationship between lifestyle and socio-demographic factors and body
      composition. METHOD: A cross-sectional study was carried out with 380 elderly
      people aged 60 and over in district 5 of Tehran, Iran. Their body composition was
      measured by Bioelectrical Impedance Analysis and the Actigraph device was used
      for assessing physical activity patterns. A three-day food recall was conducted
      to measure their intake of energy and macronutrients. Lifestyle and socio
      demographic information were collected by interview using a pretested
      questionnaire. RESULTS: Overweight, obesity and central obesity were more
      prevalent in women than in men (p<0.001). Moreover, 57.1% and 18.7% of
      participants had high and very high fat mass index, respectively. High fat mass
      index was seen in 47% of men and 37.5% of women who had normal body mass index
      (BMI). Meanwhile, age, gender, physical activity, energy intake, the percentage
      of energy from fat and protein, educational level, job, television watching time,
      smoking, chronic diseases, and taking medicine were significantly associated with
      anthropometric measurements (p<0.05). CONCLUSION: Overweight, obesity and high
      body fat percentage were common among the aged. Considering the factors that are
      significantly associated with body composition, programs that can increase their
      awareness about the dietary balance and suitable physical activity should be
      organized to address these problems.

PMID- 27045409
TI  - Application of the Random Amplified Polymorphic DNA (RAPD) Fingerprinting to
      Analyze Genetic Variation in Community Associated-Methicillin Resistant
      Staphylococcus Aureus (CA-MRSA) Isolates in Iran.
AB  - The aim of this study was to apply RAPD technique to analyze the genetic
      variability among the Iranian CA-MRSA isolates.The RAPD amplification was
      implemented on 25 strains isolated from the anterior nares of 410 healthy
      children using four randomly selected oligonucleotide primers from the stocks
      available in our laboratory, including the primers 1254, GE6, OLP6 and OLP13 from
      our stock. The amplified PCR products were detected on a 1.5% agarose gel and
      subjected to further analysis to establish the band profiles and genetic
      relationships using the Gel Compar(r) program.The Iranian CA-MRSA isolates
      produced distinct RAPD patterns which varied based on the primer used, however,
      the primer 1254 revealed highly polymorphic patterns consisting 5 discernable
      RAPD types (RT), "RT1" (12, 48%), "RT2" (8, 32%), "RT3" (3, 12%), and "RT4 and
      RT5", (a single RAPD type each, 4%). Phylogenetic analysis based on RAPD profiles
      divided most of the CA-MRSA isolates into 2 distinct but related RAPD clusters, a
      small group and two single unrelated RAPD types.This study shows that the simple
      and cost-effective but rather difficult to optimize RAPD fingerprinting could be
      used to evaluate genetic and epidemiological relationships of CA-MRSA isolates on
      condition that the patterns are obtained from carefully optimized laboratory
      tests. 

PMID- 27045410
TI  - Living with Diabetes: Experiences of Inner and Outer Sources of Beliefs in Women
      with Low Socioeconomic Status.
AB  - The purpose of this study was to examine the life experiences of nineteen Thai
      women of low socioeconomic status who were living with type 2 diabetes. A
      qualitative research design was conducted, and the women were identified by the
      snowball technique. Data was collected through semi-structured interviews, and
      processes of induction and abstraction were used for data analysis. The theme
      "keeping equilibrium of one's mind" involved two sub-themes: experiencing an
      unpredictable future and being empowered by emerged beliefs. The first sub-theme
      encompassed worries concerning health and fears of being a burden to one's
      family. The second sub-theme comprised the experiences of continuing life without
      being conquered by the disease and believing in the natural law described in
      Buddhist teachings. These findings revealed that participants could maintain a
      balance among their concerns through empowerment by inner and outer sources of
      beliefs, particularly in Buddhist teachings. Despite the vulnerable situations
      caused by diabetes and low socioeconomic status, the women remained calm, with a
      consciousness to continue their lives with the disease. The Buddhist views on
      life, specifically natural law, assisted them to consider life with diabetes as
      simply a natural course. Buddhism served as a spiritual refuge and helped the
      women to cope with their psychological burden from diabetes. These findings may
      reflect the need for health care professionals to provide more holistic care that
      would assist patients to live with their disease. Buddhist beliefs can be used as
      a tool to assist Thai patients to empower themselves successfully. 

PMID- 27045411
TI  - Barriers Facing Primary Health Care Physicians When Dealing with Emergency Cases
      in Jeddah, Saudi Arabia.
AB  - OBJECTIVES: To estimate the prevalence of emergency cases reporting to Primary
      Health Care centers (PHC), Jeddah, Saudi Arabia and to explore the barriers
      facing PHC physicians when dealing with such emergency cases. METHODS: A cross
      sectional analytic study, where all physicians working in the PHC of the Ministry
      of Health (MOH) in Jeddah; were invited to participate (n=247). The study period
      was from July 2013 till December 2013. Data were collected through two sources. 1
      A self-administered questionnaire used to determine the physicians' perceived
      competence when dealing with emergency cases. 2- A structured observation sheet
      used to evaluate availability of equipment, drugs, ambulances and other
      supporting facilities required to deal with emergency cases. RESULTS: The
      response rate was 83.4%. The physicians' age ranged between 25 and 60 years with
      a mean +/-SD of 34.4+/-7.5 years. Majority of them (83.5%) did not attend ATLS
      courses at all whereas 60.7% never attended ACLS courses. The majority (97.1%)
      had however attended BLS courses. Physicians in the age group 36-45 years, non
      Saudi, those who had SBFM, those who reported experience in working in emergency
      departments and physicians who reported more working years in PHCCs (>5 years)
      had a significant higher score of perceived level of competence in performing
      emergency skill scale than others (P<0.05). The prevalence of emergency cases
      attending PHC in Jeddah (2013) was 5.2%. CONCLUSION: Emergency services at PHC in
      Jeddah are functioning reasonably well, but require fine tuning of services and
      an upgrade in their quality.

PMID- 27045412
TI  - Isokinetic and Electromyographic Properties of Muscular Endurance in Short and
      Long-Term Type 2 Diabetes.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are subject to
      progressive reduction of muscle mass and strength. The aim of this study was to
      assess muscle forces and electromyography (EMG) indices in short and long-term
      diabetes during an isokinetic exercise. METHODS: The peak torque, work, mean
      power frequency (MPF) and root mean square (RMS) of knee flexors and extensors
      during 40 isokinetic knee extension-flexion repetitions with a velocity of 150
      degree/s were recorded. 18 patients with less than 10 years with T2DM and 12
      patients with equal and more than 10 years of disease were compared with 20
      gender, body mass index, physical activity and peripheral circulation matched
      healthy controls. RESULTS: The fatigue index and slope of line across the peak
      torque values of the knee flexor indicate that patients with long-term T2DM were
      significantly more resistant to fatigue in comparison with the two other groups
      (p<0.009). Whereas the MPF decrease during isokinetic protocol interact with
      grouping in the medial hamstring (p<0.042), but it was independent to groups in
      other muscles (p<0.0001). The increase of RMS after fatigue protocol interacted
      with sex for the medial hamstring and vastus lateralis (p<0.039) and interacted
      with group for the extensor muscles (p<0.045). DISCUSSION & CONCLUSION: It seems
      that long-term T2DM cause some neuromuscular adaptations to maintain knee flexor
      muscle performance during functional activity especially postural control.

PMID- 27045413
TI  - Investigating the Causes of Medication Errors and Strategies to Prevention of
      Them from Nurses and Nursing Student Viewpoint.
AB  - INTRODUCTION & AIM: Medication errors as a serious problem in world and one of
      the most common medical errors that threaten patient safety and may lead to even
      death of them. The purpose of this study was to investigate the causes of
      medication errors and strategies to prevention of them from nurses and nursing
      student viewpoint. MATERIALS & METHODS: This cross-sectional descriptive study
      was conducted on 327 nursing staff of khatam-al-anbia hospital and 62 intern
      nursing students in nursing and midwifery school of Zahedan, Iran, enrolled
      through the availability sampling in 2015. The data were collected by the valid
      and reliable questionnaire. To analyze the data, descriptive statistics, T-test
      and ANOVA were applied by use of SPSS16 software. FINDINGS: The results showed
      that the most common causes of medications errors in nursing were tiredness due
      increased workload (97.8%), and in nursing students were drug calculation,
      (77.4%). The most important way for prevention in nurses and nursing student
      opinion, was reducing the work pressure by increasing the personnel, proportional
      to the number and condition of patients and also creating a unit as medication
      calculation. Also there was a significant relationship between the type of ward
      and the mean of medication errors in two groups. CONCLUSION: Based on the results
      it is recommended that nurse-managers resolve the human resources problem,
      provide workshops and in-service education about preparing medications, side
      effects of drugs and pharmacological knowledge. Using electronic medications
      cards is a measure which reduces medications errors.

PMID- 27045414
TI  - Views and Attitudes of Patients in Mental Facilities Regarding Smoking.
AB  - INTRODUCTION: Smoking rates amongst people with a mental health disorder are
      significantly higher than in the general population and there is growing evidence
      to show a strong association between smoking and mental health disorders. The aim
      of the present study was to investigate views and attitudes of mental patients
      regarding smoking. MATERIAL & METHODS: The sample is composed of 356 patients
      treated in the Attica Psychiatric Hospital (a.k.a. "Dafni") as well as in other
      Units affiliated with the Hospital. The 'Smoking in psychiatric hospitals-a
      survey of patients' views' questionnaire was used in the form of semi-structured
      interviews. The PASW 18 (SPSS Inc.) package was used for the statistical analysis
      and statistical significance was set to p= 0.05. RESULTS: Overall, 40% of the
      participants were in-patients, the rest being treated in other settings, the
      average length of hospital stay was 4.4 years, and the most common diagnosis
      (61.5.%) was schizophrenia (F20, according to ICD-10), while almost all of the
      participants (97.5%) were smokers. Most patients (58.8%) said they had had a hard
      time trying to quit smoking although they had sufficient information and
      encouragement (~90%); they also reported that watching the staff smoking did not
      affect them inasmuch as watching other patients smoking (41 % vs 54.8%). 75.5% of
      the patients felt that they had no particular difficulty to quit smoking. Men
      smoked significantly more cigarettes per day compared to females (36.70 vs 30.82,
      p=0.002). There were no significant differences among males and females regarding
      previous attempts to quit smoking. Information gathered from such studies should
      be taken into account when designing systematic smoking management plans in
      mental institutions. CONCLUSION: Although almost all mental patients smoke, they
      seem to be receptive to quitting smoking, since two thirds of them have already
      tried to quit, but one-third of the patients find smoking a little or not at all
      dangerous.

PMID- 27045415
TI  - The Importance of Medication Errors Reporting in Improving the Quality of
      Clinical Care Services.
AB  - INTRODUCTION: Medication errors have significant implications on patient safety.
      Error detection through an active management and effective reporting system
      discloses medication errors and encourages safe practices. OBJECTIVES: To improve
      patient safety through determining and reducing the major causes of medication
      errors (MEs), after applying tailored preventive strategies. METHODOLOGY: A pre
      test, post-test study was conducted on all inpatients at a 177 bed hospital where
      all medication procedures in each ward were monitored by a clinical pharmacist.
      The patient files were reviewed, as well. Error reports were submitted to a
      hospital multidisciplinary committee to identify major causes of errors.
      Accordingly, corrective interventions that consisted of targeted training
      programs for nurses and physicians were conducted. RESULTS: Medication errors
      were higher during ordering/prescription stage (38.1%), followed by
      administration phase (20.9%). About 45% of errors reached the patients: 43.5%
      were harmless and 1.4% harmful. 7.7% were potential errors and more than 47%
      could be prevented. After the intervention, error rates decreased from (6.7%) to
      (3.6%) (P<=0.001). CONCLUSION: The role of a ward based clinical pharmacist with
      a hospital multidisciplinary committee was effective in recognizing, designing
      and implementing tailored interventions for reduction of medication errors. A
      systematic approach is urgently needed to decrease organizational susceptibility
      to errors, through providing required resources to monitor, analyze and implement
      effective interventions.

PMID- 27045416
TI  - Factors Affecting Hemodialysis Adequacy in Cohort of Iranian Patient with End
      Stage Renal Disease.
AB  - BACKGROUND: There are many factors that can affect dialysis adequacy; such as the
      type of vascular access, filter type, device used, and the dose, and rout of
      erythropoietin stimulation agents (ESA) used. The aim of this study was
      investigating factors affecting Hemodialysis adequacy in cohort of Iranian
      patient with end stage renal disease (ESRD). METHODS: This is a cross-sectional
      study conducted on 133 Hemodialysis patients referred to two dialysis units in
      Sistan-Baluchistan province in the cities of Zabol and Iranshahr, Iran. We have
      looked at, (the effects of the type of vascular access, the filter type, the
      device used, and the dose, route of delivery, and the type of ESA used) on
      Hemodialysis adequacy. Dialysis adequacy was calculated using kt/v formula, two
      part information questionnaire including demographic data which also including
      access type, filter type, device used for hemodialysis (HD), type of Eprex
      injection, route of administration, blood groups and hemoglobin response to ESA
      were utilized. The data was analyzed using the SPSS v16 statistical software.
      Descriptive statistical methods, Mann-Whitney statistical test, and multiple
      regressions were used when applicable. RESULTS: The range of calculated dialysis
      adequacy is 0.28 to 2.39 (units of adequacy of dialysis). 76.7% of patients are
      being dialyzed via AVF and 23.3% of patients used central venous catheters (CVC).
      There was no statistical significant difference between dialysis adequacy,
      vascular access type, device used for HD (Fresenius and B. Braun), and the filter
      used for HD (p> 0.05). However, a significant difference was observed between the
      adequacy of dialysis and Eprex injection and patients' time of dialysis (p
      <0.05). CONCLUSION: Subcutaneous ESA (Eprex) injection and dialysis shift (being
      dialyzed in the morning) can have positive impact on dialysis adequacy. Patients
      should be educated on the facts that the type of device used for HD and the
      vascular access used has no significant effects on dialysis adequacy.

PMID- 27045417
TI  - Introducing iron isomaltoside 1000 (Monofer(r))-development rationale and
      clinical experience.
AB  - Patients with chronic kidney disease (CKD) often suffer from iron deficiency
      anaemia necessitating treatment with intravenous (IV) iron. Several studies
      demonstrate that oral iron is insufficient in these patients and that IV
      supplementation is a more effective treatment. Until now, use of available
      parenteral iron preparations has been limited by dosing schedules and the need,
      in some cases, for a test dose, and despite the availability of a range of
      different IV iron compounds, there is still a need for improved compounds. The
      new IV iron, iron isomaltoside 1000 Monofer(r), is composed of iron and
      chemically modified isomalto-oligosaccharides which have a mean molecular weight
      of 1000 Da and consist predominantly of 3-5 glucose units. In contrast to
      dextrans, the carbohydrate isomaltoside 1000 is a linear and unbranched structure
      with theoretically a low immunological potential. Hence, a test dose is not
      necessary. Iron isomaltoside 1000 contains strongly bound iron within the iron
      isomaltoside formulation, which enables a controlled slow release of bioavailable
      iron to the iron-binding proteins, with potentially a reduced risk of free iron
      toxicity. This allows flexible dosing including high and rapid dosing securing
      convenient iron therapy for a wide range of patients. The development of
      Monofer(r) has been enthusiastically acknowledged by clinicians, and in 2009,
      there has been fast approval by European authorities via a decentralized
      registration procedure. This new IV iron is currently being marketed in several
      European countries. This article describes the development rationale and
      summarizes the clinical data assessing the use of iron isomaltoside 1000
      administered without a test dose by either repeated bolus injections or fast high
      single iron infusions [defined as total dose infusion (TDI)] to patients
      suffering from CKD. Since CKD is associated with a high prevalence of
      cardiovascular disease, data from a small trial applying high single doses of
      iron isomatoside 1000 in patients with chronic heart failure (CHF) are also
      reviewed. Collectively, the available data demonstrate adequate efficacy and a
      good safety profile of iron isomaltoside 1000 in CKD and CHF patients even when
      administered without a test dose and as single rapid high-dose infusions.

PMID- 27045418
TI  - The Distribution and Resistance of Pathogens Among Solid Organ Transplant
      Recipients with Pseudomonas aeruginosa Infections.
AB  - BACKGROUND: Pseudomonas aeruginosa infection remains a life-threatening
      complication after solid organ transplantation (SOT). We aimed to investigate the
      distribution and drug susceptibility of pathogens, and clinical characteristics
      of SOT recipients with Pseudomonas aeruginosa infections. MATERIAL/METHODS: A
      total of 55 SOT recipients who developed 61 episodes of Pseudomonas aeruginosa
      infections between January 1, 2003 and July 31, 2015 were retrospectively
      analyzed. The distribution and the drug susceptibility of Pseudomonas aeruginosa
      were reviewed. RESULTS: The most common site from which 61 Pseudomonas aeruginosa
      rods were isolated were the lungs (57.4%, n=37), followed by the blood (27.9%,
      n=17). There were 35, 18, and 9 recipients accompanied with a serum creatinine
      level of >1.5 mg/dL, lymphocyte count of <300/mm(3), and a serum albumin level of
      <30 g/L, respectively. Seven patients each presented with white blood cell count
      of >15,000/mm(3) and platelet count of <50,000/mm(3). There were 6 (10.9%) cases
      of septic shocks and 18 (32.7%) deaths. Antibiotic resistance rate of all
      Pseudomonas aeruginosa to 4 of 10 antibiotics investigated was more than 50%. Of
      these 61 Pseudomonas aeruginosa isolates, 47.5% were carbapenem-resistant. The
      rods were relatively sensitive to piperacillin-tazobactam, levofloxacin,
      amikacin, and cefoperazone-sulbactam (resistance rate <40%). CONCLUSIONS: The
      clinical presentation of Pseudomonas aeruginosa infections included high body
      temperature, decreased platelet count, elevated white blood cell count, a high
      nosocomial origin and mortality, and onset in the late period after
      transplantation. According to our findings, piperacillin-tazobactam,
      levofloxacin, amikacin, and cefoperazone-sulbactam, alone or combination, are
      recommended to treat SOT recipients with Pseudomonas aeruginosa infections.

PMID- 27045419
TI  - Isoptericola cucumis sp. nov., isolated from the root tissue of cucumber (Cucumis
      sativus).
AB  - A Gram-stain-positive, aerobic organism, showing an irregular cell morphology,
      was isolated from the root tissue of cucumber (Cucumis sativus) and investigated
      in detail for its taxonomic position. On the basis of the 16S rRNA gene sequence
      analysis, strain AP-38T was shown to be most closely related to Isoptericola
      variabilis (99.1 %) and Isoptericola nanjingensis (98.9 %). The 16S rRNA gene
      sequence similarity to all other species of the genus Isoptericola was <=98.5 %.
      DNA-DNA relatedness to Isoptericola variablis DSM 10177T and Isoptericola
      nanjingensis DSM 24300T was 31(reciprocal 41 %) and 34 (reciprocal 34 %),
      respectively. The diagnostic diamino acid of the peptidoglycan was l-lysine. The
      quinone system contained predominantly menaquinones MK-9(H4) and MK-9(H2). In the
      polar lipid profile, major compounds were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol and two phosphatidylinositol
      mannosides. The polyamine pattern contained the major components spermidine and
      spermine and significant amounts of tyramine. In the fatty acid profile, anteiso
      C15 : 0 and iso-C15 : 0 were present in major amounts. These data support the
      allocation of the strain to the genus Isoptericola. The results of physiological
      and biochemical characterization additionally provide phenotypic differentiation
      of strain AP-38T from I. variabilis and I. nanjingensis. AP-38T represents a
      novel species of the genus Isoptericola, for which we propose the name
      Isoptericola cucumis sp. nov., with AP-38T (= LMG 29223T=CCM 8653T) as the type
      strain. 

PMID- 27045421
TI  - Cobalt(II)-Based Single-Ion Magnets with Distorted Pseudotetrahedral [N2O2]
      Coordination: Experimental and Theoretical Investigations.
AB  - The synthesis and magnetic properties of cobalt(II) complexes with sterically
      demanding Schiff-base ligands are reported. The compounds [Co(L(Br))2] (1) and
      [Co(L(Ph))2].CH2Cl2 (2.CH2Cl2) are obtained by the reaction of cobalt(II) acetate
      with the ligands HL(Br) and HL(Ph) in a dichloromethane/methanol mixture. 1 and 2
      crystallize in the space groups P21212 and P1, respectively. X-ray diffraction
      studies revealed mononuclear constitution of both complexes. For 1, relatively
      short intermolecular Co-Co distances of 569 pm are observed. In compound 2, a
      hydrogen-bonded dichloromethane molecule is present, leading to a solvent
      aggregate with remarkable thermal stability for which desolvation is taking place
      between 150 and 210  degrees C. Magnetic measurements were performed to determine
      the zero-field-splitting (ZFS) parameter D for both complexes. Frequency
      dependent susceptibility measurements revealed slow magnetic relaxation behavior
      with spin-reversal barriers of 36 cm(-1) for 1 and 43 cm(-1) for 2 at an applied
      external field of 400 Oe. This observation is related to an increasing distortion
      of the pseudotetrahedral coordination geometry for complex 2. These distortions
      can be decomposed in two major contributions. One is the elongation effect
      described by the parameter epsilonT, which is the ratio of the averaged obtuse
      and acute bond angles. The other effect is related to a twisting distortion of
      the chelate coordination planes at the cobalt center. A comparison with
      literature examples reveals that the elongation effect seems to govern the
      overall magnetic behavior in pseudotetrahedral complexes with two bidentate
      chelate ligands. Ab initio calculations for complexes 1 and 2 using the CASPT2
      method show strong splitting of the excited (4)T2 term, which explains the
      observed strong ZFS. Spin-orbit calculations with the RASSI-SO method confirm the
      single-molecule-magnet behavior because only small transversal elements are found
      for the lowest Kramers doublet for both complexes. 

PMID- 27045420
TI  - "How is cognitive remediation training perceived by people with schizophrenia? A
      qualitative study examining personal experiences".
AB  - BACKGROUND: Meta-analytical findings have shown Cognitive Remediation (CR)
      effectiveness in augmenting cognitive and functional outcomes. Comparatively, a
      minimum amount of qualitative evidence has been reported to date. AIMS: This
      study aimed to explore the subjective experience of participants undertaking a CR
      trial. METHOD: Twenty people with schizophrenia completed a questionnaire
      facilitated interview, after having completed 20 h of CR. Thematic analysis was
      then used to identify codes and themes. RESULTS: Three themes were identified. In
      relation to reported benefits, all participants found the training to be a
      positive experience, with 70% having identified cognitive improvements, 45%
      improved motivation or confidence and 20% improved social skills. The role of the
      cognitive trainer in being supportive, adaptive and instructive was consistently
      reported as important, and most participants commented positively about the group
      format. Fewer participants had observed a transfer to real life settings, with
      improved social skills, use of cognitive strategies or aspects of everyday living
      reported by 40% of participants. CONCLUSIONS: These data highlight that all
      participants reported participation in CR to be a positive experience, with many
      reporting observed benefits following participation. Key aspects of the training
      that contributed to this positive experience were also identified and may assist
      in the further development of this intervention.

PMID- 27045422
TI  - Synthesis of 1,3-Disubstituted Imidazo[1,5-a]pyridines from Amino Acids via
      Catalytic Decarboxylative Intramolecular Cyclization.
AB  - A copper/iodine cocatalyzed decarboxylative cyclization of alpha-amino acids is
      described. Starting from the readily available amino acids and either 2
      benzoylpyridines or 2-benzoylquinolines, 1,3-disubstituted imidazo[1,5
      a]pyridines and 1,3-disubstituted imidazo[1,5-a]quinolines were prepared in
      excellent yields.

PMID- 27045423
TI  - Statistics of Natural Stochastic Textures and Their Application in Image
      Denoising.
AB  - Natural stochastic textures (NSTs), characterized by their fine details, are
      prone to corruption by artifacts, introduced during the image acquisition process
      by the combined effect of blur and noise. While many successful algorithms exist
      for image restoration and enhancement, the restoration of natural textures and
      textured images based on suitable statistical models has yet to be further
      improved. We examine the statistical properties of NST using three image
      databases. We show that the Gaussian distribution is suitable for many NST, while
      other natural textures can be properly represented by a model that separates the
      image into two layers; one of these layers contains the structural elements of
      smooth areas and edges, while the other contains the statistically Gaussian
      textural details. Based on these statistical properties, an algorithm for the
      denoising of natural images containing NST is proposed, using patch-based
      fractional Brownian motion model and regularization by means of anisotropic
      diffusion. It is illustrated that this algorithm successfully recovers both
      missing textural details and structural attributes that characterize natural
      images. The algorithm is compared with classical as well as the state-of-the-art
      denoising algorithms. 

PMID- 27045424
TI  - Gastro-intestinal tract: The leading role of mucosal immunity.
AB  - An understanding of mucosal immunity is essential for the comprehension of
      intestinal diseases that are often caused by a complex interplay between host
      factors, environmental influences and the intestinal microbiota. Not only
      improvements in endoscopic techniques, but also advances in high throughput
      sequencing technologies, have expanded knowledge of how intestinal diseases
      develop. This review discusses how the host interacts with intestinal microbiota
      by the direct contact of host receptors with highly conserved structural motifs
      or molecules of microbes and also by microbe-derived metabolites (produced by the
      microbe during adaptation to the gut environment), such as short-chain fatty
      acids, vitamins, bile acids and amino acids. These metabolites are recognised by
      metabolite-sensing receptors expressed by immune cells to influence functions of
      macrophages, dendritic cells and T cells, such as migration, conversion and
      maintenance of regulatory T cells and regulation of proinflammatory cytokine
      production, which is essential for the maintenance of intestinal homeostasis and
      the development of intestinal diseases, such as inflammatory bowel diseases.
      First interventions in these complex interactions between microbe-derived
      metabolites and the host immune system for the treatment of gastrointestinal
      diseases, such as modification of the diet, treatment with antibiotics,
      application of probiotics and faecal microbiota transplantation, have been
      introduced into the clinic. Specific targeting of metabolite sensing receptors
      for the treatment of gastrointestinal diseases is in development. In future,
      precision medicine approaches that consider individual variability in genes, the
      microbiota, the environment and lifestyle will become increasingly important for
      the care of patients with gastrointestinal diseases. 

PMID- 27045425
TI  - CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based
      antituberculosis cotreatment for a sub-Saharan Africa population.
AB  - AIM: To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment
      outcomes and provide genotype-based EFV doses recommendations during for
      tuberculosis (TB)-HIV-1 cotreatment. MATERIALS & METHODS: EFV concentrations from
      158 HIV-TB co-infected patients treated with EFV/lamivudine/zidovidine and
      rifampicin were analyzed. Genotype and CD4 and viral load data were analyzed
      using a population PK model. RESULTS: Simulated AUCs for 600 mg EFV dose were 1.2
      and 2.4-times greater than the product label for Ugandans in general and
      CYP2B6*6/*6 genotypes respectively. EFV daily doses of 450 and 250 mg for
      Ugandans and CYP2B6*6/*6 genotypes, respectively, yielded simulated exposures
      comparable to the product label. CONCLUSIONS: Around 450 and 250 mg daily doses
      might meet EFV dosing needs of HIV-TB infected Ugandans in general and
      CYP2B6*6/*6 genotypes, respectively.

PMID- 27045426
TI  - Interplay of charge density wave and multiband superconductivity in 2H-PdxTaSe2.
AB  - 2H-TaSe2 has been one of unique transition metal dichalcogenides exhibiting
      several phase transitions due to a delicate balance among competing electronic
      ground states. An unusual metallic state at high-T is sequentially followed by an
      incommensurate charge density wave (ICDW) state at ~122 K and a commensurate
      charge density wave (CCDW) state at ~90 K, and superconductivity at TC ~ 0.14 K.
      Upon systematic intercalation of Pd ions into TaSe2, we find that CCDW order is
      destabilized more rapidly than ICDW to indicate a hidden quantum phase transition
      point at x ~ 0.09-0.10. Moreover, TC shows a dramatic enhancement up to 3.3 K at
      x = 0.08, ~24 times of TC in 2H-TaSe2, in proportional to the density of states
      N(EF). Investigations of upper critical fields Hc2 in single crystals reveal
      evidences of multiband superconductivity as temperature-dependent anisotropy
      factor gammaH = , quasi-linear increase of , and an upward, positive-curvature in
      near TC. Furthermore, analysis of temperature-dependent electronic specific heat
      corroborates the presence of multiple superconducting gaps. Based on above
      findings and electronic phase diagram vs x, we propose that the increase of N(EF)
      and effective electron-phonon coupling in the vicinity of CDW quantum phase
      transition should be a key to the large enhancement of TC in PdxTaSe2. 

PMID- 27045427
TI  - Minimally invasive periodontal therapy for general practitioners.
AB  - There remains a high prevalence of mild-to-moderate forms of periodontal diseases
      in both developed and developing countries. Although many periodontal specialty
      practices currently place strong emphasis on implant surgery, periodontal plastic
      surgery and esthetics, general dentists and hygienists have often assumed more
      responsibility than periodontal specialty practices for the diagnosis, treatment,
      assessment and maintenance, and possible referral, of their patients. To address
      these current trends and challenges, this volume of Periodontology 2000 presents
      a series of topics on the basic biological principles of periodontal disease, as
      well as on approaches to diagnosis, treatment planning and treatment, in what is
      called 'conservative' or 'noninvasive' periodontal therapy. These topics include
      risk assessment of the periodontal condition; reduction, elimination and/or
      control of etiologies and risk factors, including mechanical, antimicrobial and
      host-modulation approaches; considerations for evaluation of clinical outcomes
      based on treatment approaches; and selected topics in laser therapy, halitosis
      and gingival recession. 

PMID- 27045428
TI  - Risk assessment and periodontal prevention in primary care.
AB  - The role of risk factors and risk assessment in the prediction of clinical
      periodontal outcomes, and thus in patient management, continues to be a subject
      of high professional interest and clinical relevance globally. Advances in our
      understanding of periodontal disease causality and the role of risk factors as
      predictors of future disease risk have led to the development of various
      quantitative tools to calculate risk and inform clinical decision-making. We
      review the conceptual basis for periodontal risk calculation and frame its
      potential, as well as its limitations, in the context of similar advances in
      medical care. Lastly, we discuss how broader health-policy changes are taking
      place that will probably lead to incorporation of risk-factor assessments in
      periodontal treatment planning and care management. 

PMID- 27045429
TI  - Risk factors that may modify the innate and adaptive immune responses in
      periodontal diseases.
AB  - Plaque-induced periodontal diseases occur in response to the accumulation of
      dental plaque. Disease manifestation and progression is determined by the nature
      of the immune response to the bacterial complexes in plaque. In general,
      predisposing factors for these periodontal diseases can be defined as those
      factors which retain or hinder the removal of plaque and, depending upon the
      nature of the immune response to this plaque, the disease will either remain
      stable and not progress or it may progress and result in chronic periodontitis.
      In contrast, modifying factors can be defined as those factors that alter the
      nature or course of the inflammatory lesion. These factors do not cause the
      disease but rather modify the chronic inflammatory response, which, in turn, is
      determined by the nature of the innate and adaptive immune responses and the
      local cytokine and inflammatory mediator networks. Chronic inflammation is
      characterized by vascular, cellular and repair responses within the tissues. This
      paper will focus on how common modifying factors, such as smoking, stress,
      hormonal changes, diabetes, metabolic syndrome and HIV/AIDS, influence each of
      these responses, together with treatment implications. As treatment planning in
      periodontics requires an understanding of the etiology and pathogenesis of the
      disease, it is important for all modifying factors to be taken into account. For
      some of these, such as smoking, stress and diabetic control, supportive health
      behavior advice within the dental setting should be an integral component for
      overall patient management. 

PMID- 27045431
TI  - Improving periodontal outcomes: merging clinical and behavioral science.
AB  - New data indicate that periodontal diseases are much more prevalent than
      previously thought, which means that there are large numbers of patients who will
      need to be diagnosed and treated for periodontal disease in a general dental
      practice. Oral hygiene procedures performed by patients between office visits are
      important for gingival health. No particular type of toothbrush has consistently
      been shown to have superior plaque-removal ability over another. Although studies
      on powered brushes have shown evidence for efficacy of biofilm removal and
      increased patient compliance, they are of short duration, making evaluation of
      long-term effects difficult to achieve. Interdental cleaning with dental floss
      can be effective but it is technique-sensitive. Interdental brushes have been
      shown to be superior to floss in plaque index scores, but not in gingival
      inflammation reduction. A systematic review of oral irrigation reported a
      beneficial adjunctive effect on bleeding and gingival indices and pocket depth.
      Antimicrobials in mouthrinses and toothpastes have shown significant reductions
      in plaque and gingivitis when used correctly. Even though it is considered
      essential for patients to utilize biofilm-removal techniques on a frequent basis,
      studies on adherence show that approximately 30-60% of health information is
      forgotten within 1 h, and 50% of health recommendations are not followed.
      Incorporating psychosocial aspects of behavioral change, including well
      established counseling strategies, such as motivational interviewing, may elicit
      improved patient outcomes. 

PMID- 27045432
TI  - Antibiotics/antimicrobials: systemic and local administration in the therapy of
      mild to moderately advanced periodontitis.
AB  - This review gives an update of the current scientific evidence on the efficacy of
      the adjunctive use of systemic and local antibiotics/antimicrobials in the
      treatment of periodontitis. In particular, it addresses whether their use can
      improve the results of nonsurgical mechanical therapy in mild-to-moderate forms
      of the disease. Large numbers of randomized clinical trials and systematic
      reviews with meta-analyses have clearly established that adjunctive systemic
      antibiotics, combined with mechanical debridement, offer clinical improvements
      additional to those obtained with scaling and root planing alone. These effects
      are more pronounced in aggressive periodontitis and in initially deep pockets,
      whereas more limited additional improvements, of 0.3 mm for additional pocket
      reduction and 0.2 mm for additional clinical attachment gain, have been
      documented for moderately deep sites (4-6 mm) in patients with chronic
      periodontitis. The marginal clinical benefit in patients with moderate disease
      has to be balanced against possible side effects. Notably, it has to be realized
      that an increasing number of warnings have been articulated against the
      unrestricted use of antibiotics in treating periodontal diseases because of the
      emerging global public health issue of bacterial resistance. The effects of the
      adjunctive local administration of antimicrobials have also been very well
      documented in several systematic reviews. Overall, in persistent or recurrent
      localized deep sites, the application of antimicrobials by sustained-delivery
      devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and
      0.3 mm in clinical attachment level gain. In conclusion, the slight additional
      benefits of adjunctive antimicrobials, which were shown for moderate forms of
      periodontitis, have to be balanced against their side effects and therefore their
      prescription should be limited as much as possible. 

PMID- 27045430
TI  - The tobacco-using periodontal patient: role of the dental practitioner in tobacco
      cessation and periodontal disease management.
AB  - Although the prevalence of tobacco use has declined in some parts of the world,
      tobacco use remains a persistent and, in some cases, growing problem that will
      continue to be a fundamental challenge facing dental practitioners in the decades
      ahead. Dental practitioners have a unique opportunity and professional obligation
      to be a positive influence in reducing the economic and social burden inflicted
      by tobacco use on dental and general health. In this article, the current
      noninvasive, evidence-based approaches are presented for dental practitioners to
      help patients avoid initiating tobacco use, to encourage and assist patients in
      ceasing tobacco use and to address tobacco-induced damage to periodontal
      supporting tissues. 

PMID- 27045433
TI  - Ultrasonic vs. hand instrumentation in periodontal therapy: clinical outcomes.
AB  - Periodontal disease is the most common oral disease in adults. Traditional
      nonsurgical periodontal therapy involves subgingival removal of hard and soft
      deposits on the root surface, along with maintenance of good oral hygiene.
      Nonsurgical periodontal therapy can either be definitive or part of the initial
      phase before surgical therapy. Mechanical therapy, either with hand or ultrasonic
      instrumentation, is the keystone of nonsurgical periodontal therapy. This
      requires considerable amounts of time and a high level of operator skill. The use
      of appropriate instruments greatly increases clinical efficiency. This article
      discusses the use of ultrasonic and hand instrumentation, along with recent
      advances, and the benefits of adjunctive therapy during nonsurgical periodontal
      therapy. 

PMID- 27045434
TI  - Scaling and root planing vs. conservative surgery in the treatment of chronic
      periodontitis.
AB  - A renewed interest in conservative surgical techniques has been fueled by new
      technology, changes in referral patterns to periodontists and a desire to achieve
      periodontal health in the least invasive, most cost-efficient manner possible.
      Trends suggest that an increasing amount of periodontal care is being provided in
      the offices of general dentists. If true, it is likely that patients receiving
      care in these offices will be offered simpler surgical treatment modalities that
      do not require an extensive armamentarium. The purpose of this article was to
      review the effectiveness of six relatively simple surgical techniques -
      gingivectomy, flap debridement, modified Widman flap, excisional new attachment
      procedure, modified excisional new attachment procedure and laser-assisted new
      attachment procedure - and to compare the results obtained using these procedures
      with the well-known clinical benefits of scaling and root planing. The intent was
      to determine whether the benefits of surgical procedures in the hands of most
      general dentists extend beyond those of conventional nonsurgical therapy. 

PMID- 27045435
TI  - Polymorphonuclear neutrophils in periodontitis and their possible modulation as a
      therapeutic approach.
AB  - The main focus of this review is polymorphonuclear neutrophilic granulocytes.
      Polymorphonuclear neutrophils play a pivotal role in normal host resistance to
      subgingival dental-plaque biofilm. Both hyper- and hypo-responsiveness of the
      immune system toward the microbial challenge in periodontitis have been
      described. We review polymorphonuclear neutrophil physiology with emphasis on the
      role of neutrophil functions and dysfunctions in periodontitis. Text boxes are
      given at the end of each subsection, which present the current knowledge on
      neutrophil-modulating agents as a potential therapeutic approach in
      periodontitis. 

PMID- 27045436
TI  - Post-treatment supportive care for the natural dentition and dental implants.
AB  - Long-term successful treatment of chronic periodontitis requires placement of
      patients on post-treatment recall programs known as either periodontal
      maintenance therapy or supportive periodontal therapy. Selection of the recall
      intervals must be based on the specific needs of individual patients. A single
      recall interval (e.g. 6 months) is not suitable for all patients. The main
      purpose of these programs is to prevent the recurrence of periodontitis. The
      components of every periodontal maintenance therapy program include: review of
      medical/dental histories; complete oral examination with an emphasis on the
      detection of gingival inflammation; establishing whether the maintenance program
      is working by monitoring clinical attachment levels; evaluation of oral hygiene;
      and full-mouth supragingival and subgingival debridement (i.e. biofilm removal).
      Long-term post-insertion care for dental implants also requires a similar patient
      specific recall program of supportive implant therapy. The main purposes of a
      supportive implant therapy program are to maintain a healthy peri-implant mucosa
      and thereby prevent the development of peri-implantitis. In cases in which plaque
      induced peri-implant mucositis has occurred, a well-designed supportive implant
      therapy program can help return the mucosa to a healthy state. At the current
      time there is no consensus on the optimal interventions for the treatment of peri
      implant mucositis. However, all effective supportive implant therapy programs
      emphasize meticulous oral hygiene practices, careful peri-implant examination,
      thoughtful analysis of risk factors and periodic removal of microbial deposits
      from the implants. 

PMID- 27045437
TI  - Lasers in minimally invasive periodontal and peri-implant therapy.
AB  - Laser therapy has the potential to be an effective, minimally invasive procedure
      in periodontal therapy. The aim of the present review was to survey the relevant
      literature on the clinical application of lasers as a minimally invasive
      treatment for periodontitis and peri-implant disease. Currently, there are a
      large number of published clinical studies and case reports that evaluate the
      adjunctive use of diode, carbon dioxide, neodymium-doped yttrium aluminium garnet
      (Nd:YAG), erbium-doped yttrium aluminium garnet (Er:YAG) and erbium, chromium
      doped: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) lasers or antimicrobial
      photodynamic therapy for nonsurgical and minimally invasive surgical treatment of
      periodontal pockets. These procedures are expected not only to control
      inflammation but also to provide biostimulation effects with photonic energy.
      Recent meta-analyses did not show statistically significant differences in pocket
      reduction and clinical attachment gain compared with mechanical debridement
      alone, although limited positive effects of adjunctive laser therapy were
      reported. At present, systematic literature approaches suggest that more evidence
      based studies need to be performed to support the integration of various laser
      therapies into the treatment of periodontal and peri-implant diseases. The
      disparity between previous statistical analyses and individual successful
      clinical outcomes of laser applications might reveal the necessity of developing
      optimal laser-treatment modalities of different wavelengths and better-defined
      indications for each protocol. 

PMID- 27045438
TI  - Periodontal diseases as a source of halitosis: a review of the evidence and
      treatment approaches for dentists and dental hygienists.
AB  - Bad breath (halitosis) is an important social complaint. In most cases (>=90%),
      the cause of halitosis can be found within the oral cavity. Under this
      circumstance, the term oral malodor applies. It affects both healthy and
      periodontally diseased individuals. Oral malodor is mainly caused by a microbial
      degradation of both sulfur-containing and nonsulfur-containing amino acids into
      volatile, bad-smelling gases. Anaerobic gram-negative bacteria, the same species
      that have been linked to periodontal diseases, are especially involved in this
      process, explaining why clinicians often associate oral malodor with
      periodontitis. Some volatile organic compounds render patients more susceptible
      to periodontitis and this supports the malodor-periodontitis link. This review
      investigates the interaction between oral malodor and periodontal diseases. Pro
      and con arguments regarding the mechanisms of halitosis and clinical implications
      will be presented. In general, however, the impact of tongue coatings has been
      found to be the dominant factor, besides gingivitis and periodontitis. The last
      part of this review discusses the treatment of bad breath, with different
      options. 

PMID- 27045439
TI  - Management and prevention of gingival recession.
AB  - Gingival recession is highly prevalent worldwide. It increases the risk for root
      caries and can interfere with patient comfort, function and esthetics.
      Progressive gingival recession also increases the risk of tooth loss secondary to
      clinical attachment loss. Although mitigating the causes of gingival recession
      decreases its incidence and severity, implementing practical management and
      prevention strategies in the clinical setting can be challenging. Identification
      of susceptible patients and evaluating them for the presence of modifiable risk
      exposures are essential first steps in developing action plans for appropriate
      interventions. This article reviews these steps and introduces chairside tools
      that can help in the selection of interventions designed to reduce the risk of
      future gingival recession and may also facilitate patient communication.
      Practical decision-making criteria are proposed for when and how to monitor
      gingival recession, for deciding when a patient is a candidate for surgical
      evaluation or referral to a periodontist, and, if surgery is the treatment of
      choice, what should be considered as key surgical outcome objectives. 

PMID- 27045440
TI  - Adsorption of PTCDA and C60 on KBr(001): electrostatic interaction versus
      electronic hybridization.
AB  - The adsorption of functional molecules on insulator surfaces is of great interest
      to molecular and organic electronics. Here, we present a systematic investigation
      of the geometric and electronic properties of perylene-3,4,9,10-tetracarboxylic
      3,4,9,10-dianhydride (PTCDA) and C60 on KBr(001) using density functional theory
      and non-contact atomic force microscopy to reveal the interplay of interactions
      between aromatic molecules and insulating substrates. Energetic and structural
      details are discussed, as well as electronic structures, e.g. local electronic
      density of states, (differential) charge density, and Bader charge analysis, were
      inspected. Electrostatics was found to be the primary interaction mechanism for
      systems of PTCDA and C60 adsorbed on KBr, which can be further promoted by
      electronic hybridizations of non-polar, but polarizable, molecules with
      substrates, e.g. C60/KBr(001). Electronic hybridization, depending on the
      polarizability of the pi-system, may be suppressed by introducing high electron
      affinity atoms, e.g. O, into the molecule. Besides, we investigate molecules
      adsorbed on two-layer KBr(001) covered Cu(001), in which no hybridisation was
      found between PTCDA and the metal underneath, but a C-Br-Cu hybridized state in
      C60/KBr(001)/Cu(001). Since the interaction mechanism is dominated by
      electrostatics, it is concluded that alkali-halides are interesting and important
      materials for investigation, due to the minor influence on the molecular
      electronic structure, which may inspire new research fields of electronics. 

PMID- 27045442
TI  - Dynamic thiol/disulfide homeostasis in patients with autoimmune subclinical
      hypothyroidism.
AB  - OBJECTIVE: The aim of this study was to investigate dynamic thiol/disulfide
      homeostasis in autoimmune subclinical hypothyroidism. METHODS: Forty-eight
      patients with a new diagnosis of subclinical hypothyroidism due to Hashimoto
      thyroiditis who were not yet under medical therapy, and 48 healthy control
      subjects were enrolled. Thiol/disulfide homeostasis [native thiol-disulfide
      exchanges] was measured in both groups using the automated method developed by
      Erel and Neselioglu. An absolute difference of 0.5 between the total thiol and
      native thiol concentrations revealed the disulfide bond amount. RESULTS: The
      native thiol level (p = 0.014) and native thiol/total thiol ratio (p = 0.001)
      were lower in patients with subclinical hypothyroidism than in the control group.
      Meanwhile, the disulfide level (p = 0.004), disulfide/native thiol ratio (p =
      0.001), and disulfide/total thiol (p = 0.001) ratio were higher in patients with
      subclinical hypothyroidism than in the control group. The antithyroid peroxidase
      and anti-thyroglobulin levels were positively correlated with the
      disulfide/native thiol ratio (r = 0.339, p = 0.019; r = 0.243, p = 0.023,
      respectively) and the disulfide/total thiol ratio (r = 0.133, p = 0.019; r =
      0.238, p = 0.026, respectively) and negatively correlated with the native
      thiol/total thiol ratio (r = -0.292, p = 0.004; r = -0.233, p = 0.022,
      respectively). CONCLUSION: We found that thiol/disulfide homeostasis shifted to
      disulfide formation in patients with subclinical hypothyroidism and that thyroid
      autoantibodies were positively correlated with thiol oxidation. It is not clear
      whether abnormal thiol/disulfide homeostasis is a cause or a consequence in
      Hashimoto thyroiditis. Further studies are required.

PMID- 27045443
TI  - Resilient help to switch and overlap hierarchical subsystems in a small human
      group.
AB  - Groups of social organisms in nature are resilient systems that can overcome
      unpredicted threats by helping its members. These social organisms are assumed to
      behave both autonomously and cooperatively as individuals, the helper, the helped
      and other part of a group depending on the context such as emergencies. However,
      the structure and function of these resilient actions, such as how helpers help
      colleagues and how the helper's action is effective at multiple subsystem scales
      remain unclear. Here we investigated the behaviour of organised and efficient
      small human groups in a ballgame defence, and identified three principles of
      hierarchical resilient help when under attack. First, at a present high emergency
      level, the helper simply switched the local roles in the attacked subsystem with
      the helped. Second, at an intermediate emergency level, the helpers effectively
      acted in overlapping subsystems. Third, for the most critical emergency, the
      helpers globally switched the action on the overall system. These resilient
      actions to the benefit of the system were assumed to be observed in only humans,
      which help colleagues at flexibly switched and overlapped hierarchical subsystem.
      We suggest that these multi-layered helping behaviours can help to understand
      resilient cooperation in social organisms and human groups. 

PMID- 27045444
TI  - An alerting structure: human orexin receptor 1.

PMID- 27045445
TI  - X marks the spot: PRDM9 rescues hybrid sterility by finding hidden treasure in
      the genome.

PMID- 27045446
TI  - Erratum: Reappraising the effects of artemisinin on the ATPase activity of PfATP6
      and SERCA1a E255L expressed in Xenopus laevis oocytes.

PMID- 27045447
TI  - Erratum: Exploiting the exploiter: a viral inhibitor stabilizes TAP for cryo-EM.

PMID- 27045448
TI  - The advising alliance for international and domestic graduate students:
      Measurement invariance and implications for academic stress.
AB  - We expanded the focus of a prior study of international graduate student advising
      relationships (Rice et al., 2009) to examine advising experiences of both
      international and domestic students. International (n = 434) and domestic (n =
      387) students completed the Advisory Working Alliance Inventory (AWAI-S;
      Schlosser & Gelso, 2001) and measures of advising experiences, perceived academic
      stress, and desire to change advisor. Measurement invariance analyses suggested
      that a 23-item AWAI-S showed support for scalar invariance. A bifactor structure
      showed superior fit to the 3-factor model or a second-order factor model for the
      AWAI-S. International and domestic graduate students did not differ in ratings of
      general alliance, academic stress, or desire to change advisors. General alliance
      was strongly related to less academic stress and less desire to change advisors.
      International students who felt disrespected by their advisors were more likely
      to be academically stressed than domestic students. Structured mentoring
      experiences were associated with lower stress and less desire to change, and this
      effect was similar in both international and domestic students. Overall, results
      suggested that the current level of measurement, and possibly theory development,
      regarding the advisory alliance is good at identifying generic satisfaction but
      weaker at differentiating components of the alliance.

PMID- 27045449
TI  - Building a pantheoretical model of dehumanization with transgender men:
      Integrating objectification and minority stress theories.
AB  - With a national sample of 304 transgender men, the present study tested a
      pantheoretical model of dehumanization (Moradi, 2013) with hypotheses derived
      from objectification theory (Fredrickson & Roberts, 1997), minority stress theory
      (Meyer, 2003), and prior research regarding men's body image concerns.
      Specifically, we tested common objectification theory constructs (internalization
      of sociocultural standards of attractiveness [SSA], body surveillance, body
      satisfaction) as direct and indirect predictors of compulsive exercise. We also
      examined the roles of transgender-specific minority stress variables
      antitransgender discrimination and transgender identity congruence-in the model.
      Results of a latent variable structural equation model yielded mixed support for
      the posited relations. The direct and indirect interrelations of internalization
      of SSA, body surveillance, and body satisfaction were consistent with prior
      objectification theory research, but only internalization of SSA yielded a
      significant direct relation with compulsive exercise. In addition, neither
      internalization of SSA nor body surveillance yielded significant indirect
      relations with compulsive exercise. However, antitransgender discrimination
      yielded predicted indirect relations with body surveillance, body satisfaction,
      and compulsive exercise, with transgender congruence playing a key mediating role
      in most of these relations. The implications of this pantheoretical model for
      research and practice with transgender men are discussed. (PsycINFO Database
      Record

PMID- 27045450
TI  - Effects of paired-object affordance in search tasks across the adult lifespan.
AB  - The study investigated the processes underlying the retrieval of action
      information about functional object pairs, focusing on the contribution of
      procedural and semantic knowledge. We further assessed whether the retrieval of
      action knowledge is affected by task demands and age. The contribution of
      procedural knowledge was examined by the way objects were selected, specifically
      whether active objects were selected before passive objects. The contribution of
      semantic knowledge was examined by manipulating the relation between targets and
      distracters. A touchscreen-based search task was used testing young, middle-aged,
      and elderly participants. Participants had to select by touching two targets
      among distracters using two search tasks. In an explicit action search task,
      participants had to select two objects which afforded a mutual action (e.g.,
      functional pair: hammer-nail). Implicit affordance perception was tested using a
      visual color-matching search task; participants had to select two objects with
      the same colored frame. In both tasks, half of the colored targets also afforded
      an action. Overall, middle-aged participants performed better than young and
      elderly participants, specifically in the action task. Across participants in the
      action task, accuracy was increased when the distracters were semantically
      unrelated to the functional pair, while the opposite pattern was observed in the
      color task. This effect was enhanced with increased age. In the action task all
      participants utilized procedural knowledge, i.e., selected the active object
      before the passive object. This result supports the dual-route account from
      vision to action. Semantic knowledge contributed to both the action and the color
      task, but procedural knowledge associated with the direct route was primarily
      retrieved when the task was action-relevant. Across the adulthood lifespan, the
      data show inverted U-shaped effects of age on the retrieval of action knowledge.
      Age also linearly increased the involvement of the indirect (semantic) route and
      the integration of information of the direct and the indirect routes in selection
      processes.

PMID- 27045451
TI  - Functional and structural cerebral changes in key brain regions after a
      facilitation programme for episodic future thought in relapsing-remitting
      multiple sclerosis patients.
AB  - Increasingly studied, episodic future thought (EFT) impairment negatively affects
      patients' daily life. Along these lines, working with relapsing-remitting
      multiple sclerosis (RR-MS) patients, we documented the clinical effectiveness of
      a mental visual imagery (MVI)-based facilitation programme on EFT impairment
      related to executive function difficulties. We aimed at improving the
      characterisation of the cognitive and neural underpinnings of RR-MS patients' EFT
      amelioration, by exploring the structural and functional brain changes following
      the MVI programme. Seventeen non-depressed RR-MS patients were recruited and
      randomly assigned in the (i) experimental group (n=10), who followed the MVI
      programme or in the control group (n=7), who followed a verbal control programme.
      Using an adapted version of the Autobiographical Interview to assess EFT, after
      facilitation, significant improvement was observed in the experimental group
      only. This was accompanied by increased activation in the prefrontal region
      during the generation of future events and was positively correlated with grey
      matter volume increase in this same brain area. Increased activations in the
      parahippocampal and the middle temporal gyri were also observed in the
      experimental group in post-facilitation. Likewise, functional connectivity
      changes were observed in the posterior brain regions after facilitation. Only
      minor cerebral changes were observed in the control group, likely reflecting
      practice effects. Our study showed that EFT improvement following the MVI
      programme led to functional and structural changes in brain regions sustaining
      contextual processing, visual imagery, the integration and maintenance of
      multimodal information. Taken together, these findings suggest that a cognitive
      intervention focusing on scene construction can be efficient to alleviate EFT
      impairment related to executive dysfunction. As such, this study opens the way to
      the development of tailor-made rehabilitation programmes using the different
      cognitive mechanisms involved in EFT.

PMID- 27045452
TI  - Acceptance of Serious Games in Psychotherapy: An Inquiry into the Stance of
      Therapists and Patients.
AB  - BACKGROUND: Serious games are computer or video games that contain elements that
      are specifically designed for the purpose of education or training. Serious games
      are increasingly being used within healthcare, but their introduction into and
      application in psychotherapeutic settings as an e-mental health treatment
      modality raises questions for both patients and therapists. Current research
      demonstrates the potential role and effectiveness of serious games within a
      psychotherapeutic context. However, a limited understanding of patients' and
      therapists' existing knowledge and experience of serious games, as well as of
      their readiness to utilize and apply them for the treatment of psychological
      conditions, requires further investigation. MATERIALS AND METHODS: Acceptance,
      experience, and requirements for the utilization of serious games in therapeutic
      contexts were assessed through online surveys with German-speaking patients (n =
      260) and psychotherapists (n = 234). Respondents' answers were analyzed by a
      combination of descriptive and inferential statistics by using SPSS. RESULTS:
      Current knowledge regarding serious games was very limited, with only 10.4% of
      patients and 11.5% of therapists reporting existing knowledge. However, a general
      openness toward the concept was observed: 88% of patients and 90% of therapists
      could envisage a therapeutic use. Patients (rs = 0.169, p = 0.006) who self-rated
      their level of computer and video game expertise as high were more likely to
      consider use within psychotherapy, compared with patients who self-rated their
      expertise as low. Therapists who currently play computer and video games perceive
      fewer disadvantages of serious game application in a psychotherapeutic context (p
      = 0.097). Consideration of serious game use was differentiated by the therapeutic
      approach (p = 0.003), specific mental disorders (highest rated relevant cases:
      anxiety disorders, affective disorders, disorders regarding impulse control, and
      adjustment disorders), and patient age (i.e., use with young adults was deemed
      the most appropriate by 91.8% of therapists). CONCLUSION: The application of
      serious games is conceivable for patients and therapists, especially as a
      complementary element to traditional face-to-face psychotherapy. Acceptance is
      strongly related to therapeutic context. Only a small number of therapists and
      patients agree on the possibility of using a serious game instead of face-to-face
      therapy.

PMID- 27045453
TI  - Inkjet-Printed Porous Silver Thin Film as a Cathode for a Low-Temperature Solid
      Oxide Fuel Cell.
AB  - In this work we report a porous silver thin film cathode that was fabricated by a
      simple inkjet printing process for low-temperature solid oxide fuel cell
      applications. The electrochemical performance of the inkjet-printed silver
      cathode was studied at 300-450  degrees C and was compared with that of silver
      cathodes that were fabricated by the typical sputtering method. Inkjet-printed
      silver cathodes showed lower electrochemical impedance due to their porous
      structure, which facilitated oxygen gaseous diffusion and oxygen surface
      adsorption-dissociation reactions. A typical sputtered nanoporous silver cathode
      became essentially dense after the operation and showed high impedance due to a
      lack of oxygen supply. The results of long-term fuel cell operation show that the
      cell with an inkjet-printed cathode had a more stable current output for more
      than 45 h at 400  degrees C. A porous silver cathode is required for high fuel
      cell performance, and the simple inkjet printing technique offers an alternative
      method of fabrication for such a desirable porous structure with the required
      thermal-morphological stability.

PMID- 27045454
TI  - Diagnostic performance of influenza viruses and RSV rapid antigen detection tests
      in children in tertiary care.
AB  - BACKGROUND: Rapid antigen detection tests (RADTs) are increasingly used to detect
      influenza viruses and respiratory syncytial virus (RSV). However, their
      sensitivity and specificity are a matter of debate, challenging their clinical
      usefulness. OBJECTIVES: Comparing diagnostic performances of BinaxNow Influenza
      AB((r)) (BNI) and BinaxNow RSV((r)) (BNR), to those of real-time reverse
      transcriptase PCR (RT-PCR), virus isolation and direct immunofluorescence (D-IF)
      in paediatric patients. STUDY DESIGN: Between November 2005 and September 2013,
      521 nasal washings from symptomatic children (age <5 years) attending our
      tertiary care centre were tested, with a combination of the respective assays
      using RT-PCR as gold standard. RESULTS: Sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of BNI were 69%
      (confidence interval [CI] [51-83]), 96% [94-97], 55% [39-70] and 98% [96-99]
      respectively. Of eleven false-negative samples, RT-PCR Ct-values were higher than
      all RT-PCR positive test results (27 vs 22, p=0.012). Of twenty false-positive
      samples, none were culture positive and two tested positive in D-IF. Sensitivity,
      specificity, PPV and NPV for BNR were 79% [73-85], 98% [96-99], 97% [93-99] and
      88% [84-91]. Of the 42 false-negative samples the median Ct-value was higher than
      that of all RT-PCR positive samples (31 vs 23, p<0.0001). Five false-positive
      samples were detected. Three of these tested positive for RSV in virus isolation
      and D-IF. CONCLUSIONS: RADTs have a high specificity with BNR being superior to
      BNI. However, their relative low sensitivity limits their usefulness for clinical
      decision making in a tertiary care paediatric hospital.

PMID- 27045455
TI  - Importation and outbreak of wild polioviruses from 2000 to 2014 and interruption
      of transmission in Cameroon.
AB  - BACKGROUND: Efficient implementation of the global eradication strategies
      consisting of Acute Flaccid Paralysis (AFP) surveillance and mass immunization
      campaigns led to interruption of indigenous wild poliovirus transmission in
      Cameroon in 1999. OBJECTIVES: This study describes type 1 and type 3 wild
      poliovirus (WPV) importation, incidence, geographic distribution and control
      since the original interruption of transmission in Cameroon. STUDY DESIGN: Stool
      samples from AFP patients under the age of 15 years in Cameroon were collected
      nationwide and subjected to virus isolation on RD and L20B cell cultures.
      Resulting virus isolates were typed by intratypic differentiation (ITD) and
      analysis of the VP1 coding sequence of the viral genome. Surveillance data
      originating from Cameroon between 2000 and 2014 were considered for retrospective
      descriptive analyses. RESULTS: From 2003 to 2009, multiple WPV importation events
      from neighboring countries affected mainly in the northern regions of Cameroon
      but did not led to sustained local transmission. Throughout this period, 16 WPV1
      and 5 WPV3 were detected and identified as members of multiple clusters within
      type-specific West Africa B genotypes (WEAF-B). In 2013-2014, a polio outbreak
      associated to a highly evolved ("orphan") WPV1 affected four southern regions of
      Cameroon. CONCLUSIONS: The appearance of highly evolved lineage of type 1 WPV
      suggests potential surveillance gap and underscore the need to maintain
      comprehensive polio immunization activities and sensitive surveillance systems in
      place as long as any country in the world remains endemic for WPV.

PMID- 27045456
TI  - The release of silver nanoparticles from commercial toothbrushes.
AB  - The use of silver nanoparticles (NPs) in commercial products has become
      increasingly common in the past decade, mostly due to their antimicrobial
      properties. Using Ag NP-containing articles may lead to particle release, which
      raises concern of human and environmental safety. The published literature
      addressing particle release is scarce, especially when it comes to quantifying
      exposure to NPs specifically. In this study, we have experimentally investigated
      the release of total Ag and Ag NP from commercially available toothbrushes i.e.
      biodegradable toothbrushes for adults and toothbrushes for children. Toothbrushes
      were immersed and abraded in tap water for 24h corresponding to more than the
      whole intended usage time of a toothbrush. The total amount of released Ag was
      quantified by inductively coupled plasma-mass spectrometry (ICP-MS) analysis, and
      the Ag NPs were characterized by single particle ICP-MS and transmission electron
      microscopy (TEM). The median size of the released Ag NPs ranged from 42 to 47nm,
      and the maximum total Ag release was 10.2ng per toothbrush. The adult
      toothbrushes were generally releasing more total Ag and NPs than children
      toothbrushes. In conclusion, our results indicate that the use of Ag NP
      impregnated toothbrushes can cause consumer as well as environmental exposure to
      Ag NPs.

PMID- 27045457
TI  - Elemental sulfur recovery and spatial distribution of functional bacteria and
      expressed genes under different carbon/nitrate/sulfide loadings in up-flow
      anaerobic sludge blanket reactors.
AB  - To characterize the impact of influent loading on elemental sulfur (S0) recovery
      during the denitrifying and sulfide oxidation process, three identical, lab-scale
      UASB reactors (30cm in length) were established in parallel under different
      influent acetate/nitrate/sulfide loadings, and the reactor performance and
      functional community structure were investigated. The highest S0 recovery was
      achieved at 77.9% when the acetate/nitrate/sulfide loading was set to
      1.9/1.6/0.7kgd-1m-3. Under this condition, the genera Thauera, Sulfurimonas, and
      Azoarcus were predominant at 0-30, 0-10 and 20-30cm, respectively; meanwhile, the
      sqr gene was highly expressed at 0-30cm. However, as the influent loading was
      halved and doubled, S0 recovery was decreased to 27.9% and 45.1%, respectively.
      As the loading was halved, the bacterial distribution became heterogeneous, and
      certain autotrophic sulfide oxidation genera, such as Thiobacillus, dominated,
      especially at 20-30cm. As the loading doubled, the bacterial distribution was
      relatively homogeneous with Thauera and Azoarcus being predominant, and the nirK
      and sox genes were highly expressed. The study verified the importance of
      influent loading to regulate S0 recovery, which could be achieved as Thauera and
      Sulfurimonas dominated. An influent loading that was too low or too high gave
      rise to insufficient oxidation or over-oxidation of the sulfide and low S0
      recovery performance.

PMID- 27045458
TI  - Microstructured Air Cavities as High-Index Contrast Substrates with Strong
      Diffraction for Light-Emitting Diodes.
AB  - Two-dimensional high-index-contrast dielectric gratings exhibit unconventional
      transmission and reflection due to their morphologies. For light-emitting
      devices, these characteristics help guided modes defeat total internal
      reflections, thereby enhancing the outcoupling efficiency into an ambient medium.
      However, the outcoupling ability is typically impeded by the limited index
      contrast given by pattern media. Here, we report strong-diffraction, high-index
      contrast cavity engineered substrates (CESs) in which hexagonally arranged
      hemispherical air cavities are covered with a 80 nm thick crystallized alumina
      shell. Wavelength-resolved diffraction measurements and Fourier analysis on GaN
      grown CESs reveal that the high-index-contrast air/alumina core/shell patterns
      lead to dramatic excitation of the low-order diffraction modes. Large-area (1075
      * 750 MUm(2)) blue-emitting InGaN/GaN light-emitting diodes (LEDs) fabricated on
      a 3 MUm pitch CES exhibit ~39% enhancement in the optical power compared to state
      of-the-art, patterned-sapphire-substrate LEDs, while preserving all of the
      electrical metrics that are relevant to LED devices. Full-vectorial simulations
      quantitatively demonstrate the enhanced optical power of CES LEDs and show a
      progressive increase in the extraction efficiency as the air cavity volume is
      expanded. This trend in light extraction is observed for both lateral- and flip
      chip-geometry LEDs. Measurements of far-field profiles indicate a substantial
      beaming effect for CES LEDs, despite their few-micron-pitch pattern. Near-to-far
      field transformation simulations and polarization analysis demonstrate that the
      improved extraction efficiency of CES LEDs is ascribed to the increase in
      emissions via the top escape route and to the extraction of transverse-magnetic
      polarized light.

PMID- 27045459
TI  - Have Ecosystem Services Been Oversold? A Response to Silvertown.

PMID- 27045460
TI  - Does Trophy Hunting Support Biodiversity? A Response to Di Minin et al.

PMID- 27045461
TI  - Age differences in suggestibility to contradictions of demonstrated knowledge:
      the influence of prior knowledge.
AB  - People maintain intact general knowledge into very old age and use it to support
      remembering. Interestingly, when older and younger adults encounter errors that
      contradict general knowledge, older adults suffer fewer memorial consequences:
      Older adults use fewer recently-encountered errors as answers for later knowledge
      questions. Why do older adults show this reduced suggestibility, and what role
      does their intact knowledge play? In three experiments, I examined suggestibility
      following exposure to errors in fictional stories that contradict general
      knowledge. Older adults consistently demonstrated more prior knowledge than
      younger adults but also gained access to even more across time. Additionally,
      they did not show a reduction in new learning from the stories, indicating lesser
      involvement of episodic memory failures. Critically, when knowledge was stably
      accessible, older adults relied more heavily on that knowledge compared to
      younger adults, resulting in reduced suggestibility. Implications for the broader
      role of knowledge in aging are discussed.

PMID- 27045462
TI  - Examining effects of food insecurity and food choices on health outcomes in
      households in poverty.
AB  - Evidence documenting effects of food assistance programs, household food
      insecurity, and nutrition knowledge on health outcomes is building. Using data
      from a sub-sample of adults who are 185% of the poverty line from the 2007-2008
      National Health and Nutrition Examination Survey (N = 2,171), we examine whether
      household food insecurity, food stamp take-up, and use of informal food supports
      are associated with health risk among low-income households. Findings indicate
      that while nutrition knowledge provides protection against health risk in food
      secure households, the health benefits of nutrition knowledge were not evident in
      food insecure households. We discuss these findings in light of current policy
      and practice interventions that recognize the importance of providing healthy,
      affordable food options for food insecure households.

PMID- 27045463
TI  - The Evolution of Mothers' Beliefs About Overweight and Obesity in Their Early
      School-Age Children.
AB  - OBJECTIVE: To identify changes in maternal beliefs, concerns, and perspectives
      about overweight and obesity in their children over a 2-year period. METHODS: A
      total of 37 low-income English-speaking mothers of overweight or obese children
      participated in 2 semistructured interviews, separated by about 2 years. Mean
      child age was 5.9 years at baseline and 8.2 years at follow-up. Mother and child
      anthropometric data were obtained, and mothers completed demographic
      questionnaires at both time points. Mothers' interviews were analyzed using the
      constant comparative method for longitudinal patterns of change in their
      perspectives on childhood obesity across the 2 time points. RESULTS: Six
      longitudinal patterns of change in mothers' perspectives and beliefs were
      identified: 1) mothers' identification of a weight problem in their child emerges
      gradually, 2) mothers' level of concern about their child overeating increases,
      3) mothers' concerns about consequences of obesity intensify and change over
      time, 4) mothers feel less control over their child's eating and weight, 5)
      mothers' efforts to manage eating and weight become more intentional, and 6)
      mothers are more likely to initiate conversations about weight as their child
      gets older. CONCLUSIONS: Mothers' concerns about children's weight and eating
      habits increased, and reported weight management strategies became more
      intentional over a 2-year period. Further research should consider attending to
      maternal perspectives on child weight and eating and their evolution in the
      development of family-based interventions for childhood obesity.

PMID- 27045464
TI  - Intimate imitation: Automatic motor imitation in romantic relationships.
AB  - Our relationships with romantic partners are often some of the closest and most
      important relationships that we experience in our adult lives. Interpersonal
      closeness in romantic relationships is characterised by an increased overlap
      between cognitive representations of oneself and one's partner. Importantly, this
      type of self-other overlap also occurs in the bodily domain, whereby we can
      represent another's embodied experiences in the same way as we represent our own.
      However, as yet this bodily self-other overlap has only been investigated in
      individuals unfamiliar to each other. Here, we investigate bodily self-other
      overlap between romantic partners, using automatic imitation as an example case
      of bodily overlap in the motor domain. We found that participants automatically
      imitated romantic partners significantly more than close others with whom they
      had a platonic relationship. Furthermore, imitation in these relationships was
      related to key aspects of relationship quality, as indicated by adult attachment
      style.

PMID- 27045465
TI  - Reach tracking reveals dissociable processes underlying cognitive control.
AB  - The current study uses reach tracking to investigate how cognitive control is
      implemented during online performance of the Stroop task (Experiment 1) and the
      Eriksen flanker task (Experiment 2). We demonstrate that two of the measures
      afforded by reach tracking, initiation time and reach curvature, capture distinct
      patterns of effects that have been linked to dissociable processes underlying
      cognitive control in electrophysiology and functional neuroimaging research. Our
      results suggest that initiation time reflects a response threshold adjustment
      process involving the inhibition of motor output, while reach curvature reflects
      the degree of co-activation between response alternatives registered by a
      monitoring process over the course of a trial. In addition to shedding new light
      on fundamental questions concerning how these processes contribute to the
      cognitive control of behavior, these results present a framework for future
      research to investigate how these processes function across different tasks,
      develop across the lifespan, and differ among individuals.

PMID- 27045466
TI  - Is exogenous hydrogen sulfide a relevant tool to address physiological questions
      on hydrogen sulfide?
AB  - This review challenges the use of solutions of dissolved exogenous H2S in the
      literature as a tool to determine the potential physiological functions of
      endogenous H2S as well as its putative therapeutic applications. Our major point
      of contention is that solutions of dissolved H2S are used in vitro at
      concentrations, within the high microM range, which are above the concentrations
      of dissolved H2S found in blood and tissues during lethal H2S exposure in vivo.
      In addition, since the levels of toxicity are extremely variable among cell
      types, a property that is seldom acknowledged, the physiological relevance of
      data obtained after local or in-vitro administrations of H2S at concentrations of
      few microM is far from certain. Conversely, the rate of disappearance of the
      dissolved pool of H2S in the body (being trapped or oxidized), which we found to
      be at least of several micromoles/kg/min, is so rapid in vivo that if relatively
      low quantities of H2S, i.e. few micromoles for instance, are administered, no
      change in H2S concentrations in the body is to be expected, unless toxic levels
      are used. Protocols looking at the effects of compounds slowly releasing H2S must
      also resolve a similar conundrum, as their effects must be reconciled with the
      unique ability of the blood and tissues to get rid of H2S and the steepness of
      the dose-toxic effects relationship. Only by developing a comprehensive framework
      in which H2S metabolism and toxicity will be used as a rationale to justify any
      experimental approach will we be able to bring definitive evidence supporting a
      protective role for exogenous H2S, if any, and its putative function as an
      endogenous mediator.

PMID- 27045467
TI  - Evaluating the Medical Symptom Validity Test (MSVT) in a Sample of Veterans
      Between the Ages of 18 to 64.
AB  - The purpose of the current study was to compare three potential profiles of the
      Medical Symptom Validity Test (MSVT; Pass, Genuine Memory Impairment Profile
      [GMIP], and Fail) on other freestanding and embedded performance validity tests
      (PVTs). Notably, a quantitatively computed version of the GMIP was utilized in
      this investigation. Data obtained from veterans referred for a neuropsychological
      evaluation in a metropolitan Veteran Affairs medical center were included (N =
      494). Individuals age 65 and older were not included to exclude individuals with
      dementia from this investigation. The sample revealed 222 (45%) in the Pass
      group. Of the 272 who failed the easy subtests of the MSVT, 221 (81%) met
      quantitative criteria for the GMIP and 51 (19%) were classified as Fail. The Pass
      group failed fewer freestanding and embedded PVTs and obtained higher raw scores
      on all PVTs than both GMIP and Fail groups. The differences in performances of
      the GMIP and Fail groups were minimal. Specifically, GMIP protocols failed fewer
      freestanding PVTs than the Fail group; failure on embedded PVTs did not differ
      between GMIP and Fail. The MSVT GMIP incorporates the presence of clinical
      correlates of disability to assist with this distinction, but future research
      should consider performances on other freestanding measures of performance
      validity to differentiate cognitive impairment from invalidity.

PMID- 27045468
TI  - On the exfoliating polymeric cellular dosage forms for immediate drug release.
AB  - The most prevalent pharmaceutical dosage forms at present-the oral immediate
      release tablets and capsules-are granular solids. Though effective in releasing
      drug rapidly, development and manufacture of such dosage forms are fraught with
      difficulties inherent to particulate processing. Predictable dosage form
      manufacture could be achieved by liquid-based processing, but cast solid dosage
      forms are not suitable for immediate drug release due to their resistance to
      fluid percolation. To overcome this limitation, we have recently introduced
      cellular dosage forms that can be readily prepared from polymeric melts. It has
      been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k)
      excipient and a drug exfoliate upon immersion in a dissolution medium. The drug
      is then released rapidly due to the large specific surface area of the
      exfoliations. In this work, we vary the molecular weight of the PEG excipient and
      investigate its effect on the drug release kinetics of structures with
      predominantly open-cell topology. We demonstrate that the exfoliation rate
      decreases substantially if the excipient molecular weight is increased from 12 to
      100kg/mol, which causes the drug dissolution time to increase by more than a
      factor of ten. A model is then developed to elucidate the exfoliation behavior of
      cellular structures. Diverse transport processes are considered: percolation due
      to capillarity, diffusion of dissolution medium through the cell walls, and
      viscous flow of the saturated excipient. It is found that the lower exfoliation
      rate and the longer dissolution time of the dosage forms with higher excipient
      molecular weight are primarily due to the greater viscosity of the cell walls
      after fluid penetration. 

PMID- 27045469
TI  - A novel use of friability testing for characterising ribbon milling behaviour.
AB  - Dry granulation using roll compaction (DGRC) has been increasingly adopted in the
      pharmaceutical industry due to its unique advantage of not requiring liquid
      binder and a subsequent drying process. However the DGRC process presents also
      some challenges, in particular, a high fine fraction generated during the milling
      stage significantly limits its application. Although the fines produced can be
      recycled in practice, it may lead to poor content uniformity of the final
      product. At present there is a lack of mechanistic understanding of milling of
      roll compacted ribbons. For instance, it is not clear how fines are generated,
      what are the dominant mechanisms and controlling attributes and whether any
      measurement technique can be used to characterise ribbon milling behaviour.
      Therefore, the aim of this paper was to assess whether ribbon milling behaviour
      can be assessed using some characterisation methods. For this purpose, friability
      was evaluated for ribbons made of microcrystalline cellulose (MCC) powders using
      a friability tester that was originally developed for characterising the tendency
      of pharmaceutical tablets to generate small pieces while being abraded. Granules
      were also produced by milling of the ribbons and their size distributions were
      measured. The correlation between the fine fraction of the granules with ribbon
      friability was then explored. It was found that there was a strong correlation
      between ribbon friability and the fine fraction of granules generated during
      milling. This implies that friability tests can be performed to characterise
      ribbon milling behaviour, and ribbon friability provides a good indication of the
      fraction of fines generated during ribbon milling. 

PMID- 27045470
TI  - Santosomes as natural and efficient carriers for the improvement of phycocyanin
      reepithelising ability in vitro and in vivo.
AB  - New biocarriers, named santosomes, were formulated using Santolina insularis
      essential oil and hydrogenated phosphatidylcholine. They were modified by adding
      propylene glycol, a hydrophylic penetration enhancer, and loaded with
      phycocyanin, a protein found in cyanobacteria, which possesses antioxidant and
      antiinflammatory properties. The essential oil was expected to modify the bilayer
      structure and improve the delivery and efficacy of the protein due to a
      synergistic effect of the phospholipid and S. insularis terpenes. Santosomes were
      small in size (~118nm), unilamellar and with polyhedral shape. SAXS patterns
      showed that phycocyanin strongly interacted with the polar heads of the vesicle
      bilayer. Phycocyanin-loaded vesicles did not show any toxic effect in vitro: cell
      viability was ~100% in endothelial cells and ~120% in keratinocytes, at all the
      concentrations tested. In addition, phycocyanin-loaded vesicles protected the
      cells against free radical damage. In vivo studies were performed to evaluate the
      ability of santosomes to inhibit chemically-induced oedema and inflammation in
      mice. Results demonstrated that the application of phycocyanin-loaded santosomes
      produced an evident amelioration of the skin lesion, confirming their great
      potential for wound healing. 

PMID- 27045471
TI  - NAD(P)H:Quinone Oxidoreductase-1 Expression Sensitizes Malignant Melanoma Cells
      to the HSP90 Inhibitor 17-AAG.
AB  - The KEAP1-NRF2 pathway regulates cellular redox homeostasis by transcriptional
      induction of genes associated with antioxidant synthesis and detoxification in
      response to oxidative stress. Previously, we reported that KEAP1 mutation elicits
      constitutive NRF2 activation and resistance to cisplatin (CDDP) and dacarbazine
      (DTIC) in human melanomas. The present study was conducted to clarify whether an
      HSP90 inhibitor, 17-AAG, efficiently eliminates melanoma with KEAP1 mutation, as
      the NRF2 target gene, NQO1, is a key enzyme in 17-AAG bioactivation. In melanoma
      and non-small cell lung carcinoma cell lines with or without KEAP1 mutations,
      NQO1 expression and 17-AAG sensitivity are inversely correlated. NQO1 is highly
      expressed in normal melanocytes and in several melanoma cell lines despite the
      presence of wild-type KEAP1, and the NQO1 expression is dependent on NRF2
      activation. Because either CDDP or DTIC produces reactive oxygen species that
      activate NRF2, we determined whether these agents would sensitize NQO1-low
      melanoma cells to 17-AAG. Synergistic cytotoxicity of the 17-AAG and CDDP
      combination was detected in four out of five NQO1-low cell lines, but not in the
      cell line with KEAP1 mutation. These data indicate that 17-AAG could be a
      potential chemotherapeutic agent for melanoma with KEAP1 mutation or NQO1
      expression. 

PMID- 27045472
TI  - Mutant p53 proteins alter cancer cell secretome and tumour microenvironment:
      Involvement in cancer invasion and metastasis.
AB  - An ever-increasing number of studies highlight the role of mutant p53 proteins in
      the alteration of cancer cell secretome and in the modification of tumour
      microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge
      of the molecular mechanisms underlying the interplay between mutant p53 proteins
      and the microenvironment is becoming fundamental for the identification of both
      efficient anticancer therapeutic strategies and novel serum biomarkers. In this
      review, we summarize the novel findings concerning the regulation of secreted
      molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight
      data from available literature, suggesting that mutant p53 proteins are able to
      (i) alter the secretion of enzymes involved in the modulation of extracellular
      matrix components; (ii) alter the secretion of inflammatory cytokines; (iii)
      increase the extracellular acidification; and (iv) regulate the crosstalk between
      cancer and stromal cells.

PMID- 27045473
TI  - ASC-J9((r)), and not Casodex or Enzalutamide, suppresses prostate cancer
      stem/progenitor cell invasion via altering the EZH2-STAT3 signals.
AB  - Early studies suggested that prostate cancer (PCa) stem/progenitor (S/P) cells
      might play key roles to promote the tumor initiation and metastasis. Yet their
      linkage to the failure of androgen deprivation therapy (ADT), however, remains
      unclear. Here we demonstrated that the ADT with anti-androgens Casodex (also
      known as Bicalutamide) and Enzalutamide (also known as MDV3100), but not the
      newly identified AR degradation enhancer, ASC-J9((r)), increased PCa S/P
      population, which might then lead to enhance the PCa cell invasion. Targeting AR
      with ASC-J9((r)), and not targeting androgens with Casodex or Enzalutamide, led
      to suppress PCa S/P cell invasion. Mechanism dissection revealed ASC-J9((r))
      could suppress S/P cell invasion via altering the EZH2/STAT3 and/or
      AKT/EZH2/STAT3 signals. Together, these results suggest that targeting PCa S/P
      cells with ASC-J9((r)) or inhibitors to interrupt the EZH2/STAT3 and/or
      Akt/EZH2/STAT3 signals may become a new therapy to overcome the unwanted side
      effects of Casodex or Enzalutamide to further suppress the PCa metastasis.

PMID- 27045474
TI  - Challenges and opportunities for siRNA-based cancer treatment.
AB  - As one of the life-threatening diseases involving multi-step genetic and
      epigenetic disorders, cancer has long been a dynamic research area for siRNA
      based therapy as half of the current siRNA-based clinical trials are involved in
      oncology. However, despite consistent enthusiasm in the academic world, siRNA
      based cancer treatment still faces obstacles and difficulties in clinical
      development. In this article, we discuss key challenges facing siRNA-based cancer
      treatment revealed from recent clinical and preclinical studies, including
      chemical modification, tumour penetration, endosomal escape, target selection and
      off-target effects. In addition, opportunities and avenues for translating siRNA
      technology from bench to oncologic clinics are explored.

PMID- 27045475
TI  - Hepatocellular carcinoma: Mouse models and the potential roles of proteases.
AB  - Primary liver cancer is the second most common cause of mortality from cancer.
      The most common models of hepatocellular carcinoma, which use a chemical and/or
      metabolic insult, xenograft, or genetic manipulation, are discussed in this
      review. In the tumour microenvironment lymphocytes, fibroblasts, endothelial
      cells and antigen presenting cells are important determinants of cell fate. These
      cells make a range of proteases that modify the biological activity of other
      proteins, particularly extracellular matrix proteins that alter cell migration of
      tumour cells, fibroblasts and leucocytes, and chemokines that alter leucocyte
      migration. The DPP4 family of post-proline peptidase enzymes modifies cell
      movement and the activities of many bioactive molecules including growth factors
      and chemokines.

PMID- 27045476
TI  - Short-chain ceramides depress integrin cell surface expression and function in
      colorectal cancer cells.
AB  - Colorectal cancer (CRC) is highly metastatic, significantly so to liver, a
      characteristic that embodies one of the most challenging aspects of treatment.
      The integrin family of cell-cell and cell-matrix adhesion receptors plays a
      central role in migration and invasion, functions that underlie metastatic
      potential. In the present work we sought to determine the impact of ceramide,
      which plays a key modulatory role in cancer suppression, on integrin cell surface
      expression and function in CRC cells in order to reveal possible ceramide-centric
      effects on tumor cell motility. Human CRC cells LoVo, HT-29, and HCT-116 were
      employed, which represent lines established from primary and metastatic sites. A
      cell-permeable, short-chain analog, C6-ceramide, was used as ceramide mimic.
      Exposure of cells to C6-ceramide (24 h) promoted a dose-dependent (2.5-10 uM)
      decrease in the expression of cell surface beta1 and beta4 integrin subunits in
      all cell lines; at 10 uM C6-ceramide, the decreases ranged from 30 to 50% of the
      control. Expression of cell surface alphaVbeta6 integrin, which is associated
      with advanced invasion in CRC, was also suppressed by C6-ceramide. Decreases in
      integrin expression translated to diminished cellular adhesion, 50% of the
      control at 5 uM C6-ceramide, and markedly reduced cellular migration,
      approximately 30-40% of the control in all cell lines. Physicochemical
      examination revealed potent efficacy of nano-formulated C6-ceramide, but inferior
      activity of dihydro-C6-ceramide and L-C6-ceramide, compared to the unsaturated
      counterpart and the natural d-enantiomer, respectively. These studies demonstrate
      novel actions of ceramides that may have application in suppression of tumor
      metastasis, in addition to their known tumor suppressor effects.

PMID- 27045477
TI  - Rare ATAD5 missense variants in breast and ovarian cancer patients.
AB  - ATAD5/ELG1 is a protein crucially involved in replication and maintenance of
      genome stability. ATAD5 has recently been identified as a genomic risk locus for
      both breast and ovarian cancer through genome-wide association studies. We aimed
      to investigate the spectrum of coding ATAD5 germ-line mutations in hospital-based
      series of patients with triple-negative breast cancer or serous ovarian cancer
      compared with healthy controls. The ATAD5 coding and adjacent splice site regions
      were analyzed by targeted next-generation sequencing of DNA samples from 273
      cancer patients, including 114 patients with triple-negative breast cancer and
      159 patients with serous epithelial ovarian cancer, and from 276 healthy females.
      Among 42 different variants identified, twenty-two were rare missense
      substitutions, of which 14 were classified as pathogenic by at least one in
      silico prediction tool. Three of four novel missense substitutions (p.S354I,
      p.H974R and p.K1466N) were predicted to be pathogenic and were all identified in
      ovarian cancer patients. Overall, rare missense variants with predicted
      pathogenicity tended to be enriched in ovarian cancer patients (14/159) versus
      controls (11/276) (p = 0.05, 2df). While truncating germ-line variants in ATAD5
      were not detected, it remains possible that several rare missense variants
      contribute to genetic susceptibility toward epithelial ovarian carcinomas.

PMID- 27045478
TI  - MicroRNAs as novel targets and tools in cancer therapy.
AB  - MicroRNAs (miRNAs) are currently experiencing a renewed peak of attention not
      only as diagnostics but also especially as highly promising novel targets or
      tools for clinical therapy in several different malignant diseases. Moreover, the
      recent discovery of competing endogenous RNAs (ceRNAs) as novel miRNA-regulators
      has contributed exciting insights in this regard. Therefore, this review
      summarizes and discusses the latest findings on (1) how miRNAs have become
      therapeutic targets of diverse synthetic antagonists, (2) how novel endogenous
      regulators of miRNAs such as ceRNAs or pseudogenes could emerge as therapeutics
      scavenging oncogenic miRNAs and (3) how miRNAs themselves are already, and will
      increasingly be, used as therapeutics. Recent advances on the importance of miRNA
      target affinity and the subcellular localization of miRNAs are also discussed.
      The potential of these developments in different tumor entities and particular
      hallmarks of cancer such as metastasis, disease progression, interactions with
      the tumor microenvironment, or cancer stem cells are equally highlighted.

PMID- 27045479
TI  - Biosensing made easy with PEG-targeted bi-specific antibodies.
AB  - Whilst recent advances in nanotechnology have yielded many new biosensing
      capabilities, innovative biological attachment and detection modalities remain
      relatively underdeveloped. Bi-specific antibodies (bsAbs)--which exhibit binding
      capability for two separate targets--offer an inherent advantage over
      conventional antibody reagents by significantly simplifying sensor surface
      preparation. Herein, we report the deployment of bsAbs for simultaneous
      attachment to a polymer-coated transducer and label-free, electrochemical (EC)
      detection of target antigens.

PMID- 27045480
TI  - Two-Stage Revision Anterior Cruciate Ligament Reconstruction.
AB  - The number of primary anterior cruciate ligament (ACL) tears is rapidly
      increasing. In patients who wish to return to their preoperative level of
      function, specifically as it pertains to participation in sports, the gold
      standard of treatment following an ACL tear remains an anterior cruciate ligament
      (ACL) reconstruction. Despite a majority of good/excellent results following
      primary ACL reconstruction, there is a growing subset of patients with persistent
      or recurrent functional instability who require revision ACL reconstruction.
      Preoperative planning for revision ACL reconstruction requires a careful
      understanding of the root cause of ACL failure, including possible technical
      causes of primary ACL failure and the presence of combined knee pathology that
      was not addressed at the index ACL reconstruction. The decision to perform 2
      stage revision ACL reconstruction is multifactorial and is reached by technical
      considerations that may make a 1-stage revision less optimal, including tunnel
      widening, arthrofibrosis, active infection, and others. Concomitant knee
      pathology such as meniscal deficiency, malalignment (including an increase in
      posterior tibial slope), chondral lesions, and other ligamentous laxity may also
      require a staged approach to treatment. This evidence-based review covers the
      indications for 2-stage revision ACL reconstruction, surgical techniques,
      evidence for and technique of bone grafting prior ACL tunnels, and outcomes of 2
      stage revision stratified by initial cause of ACL reconstruction failure. With
      proper preoperative planning and an understanding of the cause of failure
      following the primary ACL reconstruction, revision ACL reconstruction can offer
      excellent outcomes in the motivated patient. [Orthopedics. 2016; 39(3):e456
      e464.]. 

PMID- 27045481
TI  - Smooth Pins Reinforcing Static Cement Spacers for Infected Total Knee
      Arthroplasty Are Not Safe.
AB  - Prosthetic joint infection is one of the most dreaded complications following
      elective lower extremity primary total joint arthroplasty, resulting in
      substantial pain, disability, and health care costs. Both static and articulating
      antibiotic-impregnated spacers have been used in the management of 2-stage
      revision for infected total knee arthroplasty, which remains the gold standard
      for treatment of these infections. Articulating spacers may provide theoretical
      benefits with regard to improved range of motion after reimplantation secondary
      to less scar formations and soft tissue contractures. However, static spacers may
      be necessary to overcome instability associated with substantial bone defects,
      incompetent extensor mechanisms, and collateral ligament insufficiencies. In
      these scenarios, static spacers are often reinforced with intramedullary rods or
      Steinmann pins to provide additional knee stability, improve construct strength,
      maintain extension, and avoid flexion contractures. This case report describes an
      extremely rare case of migration of smooth pins through the posterior tibia into
      the calf following static spacer use in a 48-year-old man. Various mechanical and
      systemic complications have been reported in up to 50% of patients with the use
      of polymethyl methacrylate spacer devices, such as acute renal failure, allergic
      reactions from antibiotic use, stiffness, bone loss, fractures, and dislocations.
      However, to the best of the authors' knowledge, this complication of hardware
      migration has not been reported previously in the literature. The authors believe
      that orthopedic surgeons should consider the use of threaded pin dowels or
      intramedullary rods to avoid this potential untoward complication. [Orthopedics.
      2016; 39(3):e553-e557.]. 

PMID- 27045482
TI  - A 15-Year-Old Male Baseball Player With a Mass in the Brachialis Muscle.
AB  - A 15-year-old boy presented with a mass in his right arm after suffering a minor
      injury playing baseball. He had been diagnosed with a hematoma. There was no
      other outstanding medical/surgical history. Magnetic resonance images showed a
      heterogeneous mass arising from the brachialis muscle that mainly enhanced
      peripherally with extremely scant internal nodular enhancement. Core needle
      biopsy cells were positive for CD31 and CD34, markers for atypical endothelial
      cells, as well as MIB-1 and p53. The final diagnosis was an angiosarcoma of the
      brachialis muscle. Pediatric angiosarcoma, particularly within deep tissue, is
      exceedingly rare. Histological and immunohistochemical modalities led to the
      diagnosis. Magnetic resonance images suggested a mass with a large
      cystic/hemorrhagic space that could have been misconstrued as a hematoma had
      there been absolutely no nodular or septal enhancement. The patient underwent
      neoadjuvant chemotherapy and radiation before undergoing limb-sparing surgery
      that included resection of the mass with the brachialis muscle and short head of
      the biceps muscle. Neoadjuvant treatment was deemed successful due to a drastic
      reduction in the size of the tumor and 95% tumor necrosis. The patient was
      disease free 2 years postoperatively. There had been no local/systemic
      recurrences. He was pain free, had normal elbow function, and had returned to
      playing baseball. It is important to be extremely suspicious when a patient
      presents with a hemorrhagic, painless, enlarging mass after sustaining minor
      trauma. A careful and meticulous biopsy must be completed to achieve the correct
      diagnosis. Magnetic resonance imaging with gadolinium is recommended for
      evaluation because these masses can be often misinterpreted as hematomas.
      [Orthopedics. 2016; 39(3):e545-e548.]. 

PMID- 27045483
TI  - Surgical Management of Proximal Humeral Fractures: The Emerging Role of Reverse
      Total Shoulder Arthroplasty.
AB  - Acute proximal humeral fractures are common injuries in elderly patients. These
      fractures can lead to significant pain and functional loss. Nonoperative
      treatment offers high rates of satisfactory function and pain relief in the
      majority of fractures, particularly in elderly patients. Open reduction and
      internal fixation, closed reduction and percutaneous pinning, and
      hemiarthroplasty are used for treating displaced proximal humeral fractures,
      depending on patient and fracture characteristics. Recently, reverse total
      shoulder arthroplasty has gained popularity for treatment of complex proximal
      humeral fractures due to a rapid recovery of active elevation and activities of
      daily living function. Although complications remain a concern, early results of
      reverse total shoulder arthroplasty for proximal humeral fractures have been
      promising. Future comparative outcome studies are needed to define the
      indications for reverse total shoulder arthroplasty instead of nonoperative and
      other operative options. Optimal treatment of proximal humeral fractures requires
      clinical judgment based on fracture characteristics, bone quality, patient
      factors, and surgeon experience with the array of available techniques.
      [Orthopedics. 2016; 39(3):e465-e473.]. 

PMID- 27045484
TI  - Outcomes Following Radial Head Arthroplasty.
AB  - Most current series of radial head arthroplasty include small numbers of patients
      with short- to medium-term follow-up and significant heterogeneity in patients,
      treatments, and outcome measures. The purpose of this systematic review was to
      review outcomes for radial head arthroplasty based on injury chronicity, injury
      pattern, and type of implant used. The authors systematically searched electronic
      databases for studies containing radial head arthroplasty or radial head
      replacement and identified 19 studies for inclusion in the analysis. For each
      included study, a composite mean was obtained for Mayo Elbow Performance Score
      (MEPS) and range of motion. Outcomes were said to differ significantly if their
      confidence intervals did not overlap. The MEPS for acute treatment (90) was
      higher than that for delayed treatment (81). There was no difference in the
      pooled MEPS between the isolated (89) and complex injury pattern (87) groups or
      implant material. There was no difference in range of motion between the acute
      and delayed or isolated and complex groups, but the average degree of pronation
      was higher in patients treated with titanium implants (76 degrees ) compared with
      cobalt chromium implants (66 degrees ). This systematic review suggests that
      outcomes are improved following acute arthroplasty for treatment of radial head
      fractures compared with delayed treatment, based on MEPS. The lack of other
      significant differences detected is likely due to the significant heterogeneity
      and inadequate power in current studies. Further prospective studies isolating
      the different variables will be needed to determine their true effect on
      outcomes. [Orthopedics. 2016; 39(3):153-160.]. 

PMID- 27045485
TI  - Bilateral Total Knee Arthroplasty in a 15 Year Old With Skeletal Dysplasia and
      Open Physes.
AB  - There are limited reports of total knee arthroplasty (TKA) in the pediatric
      population. The use of constrained, stemmed components is particularly unusual in
      the setting of open physes due to concerns with growth arrest and implant
      survivorship. The current authors describe a 15-year-old boy with open growth
      plates and an epiphyseal dysplasia-like condition affecting the knees
      bilaterally. He had no other significant medical or orthopedic conditions and his
      genetic workup was negative. He had severe knee pain and a bilateral 40 degrees 
      valgus with severe lateral compartment arthritis. Conservative treatment provided
      no symptom relief, and the patient had been wheelchair bound for 18 months prior
      to presentation. Treatment with simultaneous bilateral TKA using cemented,
      stemmed, and constrained components was undertaken. There were no intraoperative
      complications, and his final follow-up was at 5.6 years postoperatively.
      Radiographic evaluation at follow-up showed that components were well placed with
      no loosening. The patient had pain-free motion and a perfect Knee injury and
      Osteoarthritis Outcome Score. Based on the review of the literature and the
      outcomes of this case, the authors believe simultaneous bilateral TKA using
      cemented, stemmed, and constrained components is a reasonable option for joint
      reconstruction in the pediatric patient with open physes who also has significant
      arthritis and deformity not of oncologic origin. [Orthopedics. 2016; 39(3):e549
      e552.]. 

PMID- 27045487
TI  - Physical Therapy Treatment Of Chronic Neck Pain A Discussion And Case Study:
      Using Dry Needling And Battlefield Acupuncture.
AB  - PURPOSE: Chronic mechanical neck pain can have a complex clinical presentation
      and is often difficult to treat. This case study illustrates a successful
      physical therapy treatment approach using dry needling and auricular acupuncture
      techniques. CASE REPORT: A 51-year-old active-duty, male US Marine was treated by
      a physical therapist in a direct-access military clinic for chronic neck pain
      poorly responsive to previous physical therapy, pharmacologic, and surgical
      interventions. Needling techniques were combined with standard physical therapy
      interventions to address the comprehensive needs of the patient. Within five
      treatments, the patient reported reduced pain levels from 8-9/10 to 0-2/10,
      improved sleep quality, and increased function with daily activities. Over
      several months, the patient reduced multiple medication use by greater than 85%.
      The effects of treatment were lasting, and the patient accomplished a successful
      transition to an independent maintenance program. CONCLUSION: Needling techniques
      have the potential to expedite favorable physical therapy outcomes for active
      duty service members suffering from chronic mechanical and degenerative neck
      pain. The dramatic improvements observed in this case warrant additional
      exploration of treatment efficacy and delineation of best practices in the
      delivery of these techniques.

PMID- 27045486
TI  - Environmental Mapping of Paracoccidioides spp. in Brazil Reveals New Clues into
      Genetic Diversity, Biogeography and Wild Host Association.
AB  - BACKGROUND: Paracoccidioides brasiliensis and Paracoccidioides lutzii are the
      etiological agents of Paracoccidioidomycosis (PCM), and are easily isolated from
      human patients. However, due to human migration and a long latency period,
      clinical isolates do not reflect the spatial distribution of these pathogens.
      Molecular detection of P. brasiliensis and P. lutzii from soil, as well as their
      isolation from wild animals such as armadillos, are important for monitoring
      their environmental and geographical distribution. This study aimed to detect
      and, for the first time, evaluate the genetic diversity of P. brasiliensis and P.
      lutzii for Paracoccidioidomycosis in endemic and non-endemic areas of the
      environment, by using Nested PCR and in situ hybridization techniques.
      METHODS/PRINCIPAL FINDINGS: Aerosol (n = 16) and soil (n = 34) samples from
      armadillo burrows, as well as armadillos (n = 7) were collected in endemic and
      non-endemic areas of PCM in the Southeastern, Midwestern and Northern regions of
      Brazil. Both P. brasiliensis and P. lutzii were detected in soil (67.5%) and
      aerosols (81%) by PCR of Internal Transcribed Spacer (ITS) region (60%), and also
      by in situ hybridization (83%). Fungal isolation from armadillo tissues was not
      possible. Sequences from both species of P. brasiliensis and P. lutzii were
      detected in all regions. In addition, we identified genetic Paracoccidioides
      variants in soil and aerosol samples which have never been reported before in
      clinical or armadillo samples, suggesting greater genetic variability in the
      environment than in vertebrate hosts. CONCLUSIONS/SIGNIFICANCE: Data may reflect
      the actual occurrence of Paracoccidioides species in their saprobic habitat,
      despite their absence/non-detection in seven armadillos evaluated in regions with
      high prevalence of PCM infection by P. lutzii. These results may indicate a
      possible ecological difference between P. brasiliensis and P. lutzii concerning
      their wild hosts.

PMID- 27045488
TI  - Compensatory Reserve for Early and Accurate Prediction of Hemodynamic Compromise:
      Case Studies for Clinical Utility in Acute Care and Physical Performance.
AB  - BACKGROUND: Humans are able to compensate for significant loss of their
      circulating blood volume, allowing vital signs to remain relatively stable until
      compensatory mechanisms are overwhelmed. The authors present several clinical and
      performance case studies in an effort to demonstrate real-time measurements of an
      individual's reserve to compensate for acute changes in circulating blood volume.
      This measurement is referred to as the Compensatory Reserve Index (CRI). METHODS:
      We identified seven clinical and two physical performance conditions relevant to
      military casualty and operational medicine as models of intravascular volume
      compromise. Retrospective analysis of photoplethysmogram (PPG) waveform features
      was used to calculate CRI, where 1 represents supine normovolemia and 0
      represents hemodynamic decompensation. RESULTS: All cases had CRI values
      suggestive of volume compromise (<0.6) not otherwise evident by heart rate and
      systolic blood pressure. CRI decreased with reduced central blood volume and
      increased with restored volume (e.g., fluid resuscitation). CONCLUSION: The
      results from these case studies demonstrate that machine-learning techniques can
      be used to (1) identify a clinical or physiologic status of individuals through
      real-time measures of changes in PPG waveform features that result from
      compromise to circulating blood volume and (2) signal progression toward
      hemodynamic instability, with opportunity for early and effective intervention,
      well in advance of changes in traditional vital signs.

PMID- 27045489
TI  - Short Report Comparing Generation 6 Versus Prototype Generation 7 Combat
      Application Tourniquet(r) in a Manikin Hemorrhage Model.
AB  - BACKGROUND: The Combat Application Tourniquet(r) (C-A-T) is the standard-issue
      military tourniquet used in first aid in 2015, and the current model is called
      Generation 6. Soldiers in the field, however, have been asking for design changes
      in a possible Generation 7 to improve ease of use. This study compared the
      differential performance in use of the C-A-T in two designs: Generation 6 (C-A-T
      6) versus a prototype Generation 7 (C-A-T 7). METHODS: A laboratory experiment
      was designed to test the performance of two tourniquet designs in hemorrhage
      control, ease of use, and user preference. Ten users of the two C-A-T models
      placed them on a manikin thigh to stop simulated bleeding. Users included trauma
      researchers and instructors of US Army student medics. Ten users conducted 20
      tests (10 each of both designs). RESULTS: Most results were not statistically
      significant in their difference by C-A-T design. The mean difference in blood
      loss was statistically significant (rho = .03) in that the C-A-T 7 performed
      better than the C-A-T 6, but only in the mixed statistical model analysis of
      variance, which accounted for user effects. The difference in ease-of-use score
      was statistically significant (rho = .002); the C-A-T 7 was easier. All users
      preferred the C-A-T 7. CONCLUSION: In each measure, the C-A-T Generation 7
      prototype performed similar or better than Generation 6, was easier to use, and
      was preferred.

PMID- 27045490
TI  - Management of External Hemorrhage in Tactical Combat Casualty Care: The
      Adjunctive Use of XStatTM Compressed Hemostatic Sponges: TCCC Guidelines Change
      15-03.
AB  - Exsanguination from wounds in the so-called junctional regions of the body (i.e.,
      the neck, the axilla, and the groin) was responsible for 19% of the combat
      fatalities who died from potentially survivable wounds sustained in Afghanistan
      or Iraq during 2001 to 2011. The development of improved techniques and
      technology to manage junctional hemorrhage has been identified in the past as a
      high-priority item by the Committee on Tactical Combat Casualty Care (CoTCCC) and
      the Army Surgeon General's Dismounted Complex Blast Injury (DCBI) Task Force.
      Additionally, prehospital care providers have had limited options with which to
      manage hemorrhage resulting from deep, narrow-track, penetrating trauma. XStatTM
      is a new product recently approved by the US Food and Drug Administration as a
      hemostatic adjunct to aid in the control of bleeding from junctional wounds in
      the groin or axilla. XStat has now been recommended by the CoTCCC as another tool
      for the combat medical provider to use in the management of junctional
      hemorrhage. The evidence that supports adding XStat to the TCCC Guidelines for
      the treatment of external hemorrhage is summarized in this paper. 

PMID- 27045491
TI  - Preliminary Comparison of New and Established Tactical Tourniquets in a Manikin
      Hemorrhage Model.
AB  - BACKGROUND: Emergency tourniquet use has been associated with hemorrhage control
      and improved survival during the wars since 2001. The purpose of the present
      study is to compare the differential performance of two new tactical tourniquets
      with the standard-issue tourniquet to provide preliminary evidence to guide
      decisions on device development. METHODS: A laboratory experiment was designed to
      test the effectiveness of tourniquets on a manikin thigh. Three models of
      tourniquets were assessed. The Rapid Application Tourniquet System (RATS) and the
      Tactical Mechanical Tourniquet (TMT) were compared with the standard-issue Combat
      Application Tourniquet((r)) (C-A-T). Two users conducted 30 tests each. RESULTS:
      Percentages for effectiveness (hemorrhage control, yes/no) and distal pulse
      cessation did not differ significantly by model. When compared with the RATS, the
      C-A-T performed better (rho < .001) for time to hemorrhage control and fluid
      loss. The C-A-T and TMT had comparable responses for most measures, but the C-A-T
      applied more pressure (rho = .04) than did the TMT for hemorrhage control.
      CONCLUSION: All three tactical tourniquets showed substantial capacity for
      hemorrhage control. However, the two new tourniquet models (RATS and TMT) did not
      offer any improvement over the C-A-T, which is currently issued to military
      services. Indeed, one of the new models, the RATS, was inferior to the C-A-T in
      terms of speed of application and simulated loss of blood. Opportunities were
      detected for refinements in design of the two new tourniquets that may offer
      future improvements in their performance.

PMID- 27045492
TI  - Testing of Junctional Tourniquets by Medics of the Israeli Defense Force in
      Control of Simulated Groin Hemorrhage.
AB  - BACKGROUND: Junctional hemorrhage is a common cause of battlefield death but
      little is known about testing of junctional tourniquet models by medics. The
      purpose of the testing described herein is to assess military experience in
      junctional tourniquet use in simulated prehospital care. METHODS: Fourteen medics
      were to use the following four junctional tourniquets: Combat Ready Clamp (CRoC),
      Abdominal Aortic Junctional Tourniquet (AAJT), Junctional Emergency Treatment
      Tool (JETT), and SAM Junctional Tourniquet (SJT). The five assessment categories
      were safety, effectiveness, time to effectiveness, and two categories of user
      preference: (1) by all models assessed, and (2) by only the model most preferred.
      Users ranked preference by answering, "If you had to go to war today and you
      could only choose one, which tourniquet would you choose to bring?" RESULTS: All
      tourniquet uses were safe. By the time the first five testers were done, all
      three AAJT models had been broken. CRoC and AAJT had the highest percentage
      effectiveness as their difference was not statistically significant. SJT and JETT
      had fastest mean times to effectiveness as their difference was not significant.
      For preference, using each user's ranking of all models assessed, SJT and AAJT
      were most preferred as their difference was not significant. For each user's most
      preferred model, SJT, AAJT, and JETT were most preferred as their difference was
      not significant. CONCLUSION: In the five assessment categories, multiple
      tourniquet models performed similarly well; SJT and AAJT performed best in four
      categories, JETT was best in three, and CRoC was best in two. Differences between
      the top-ranked models in each category were not statistically significant.

PMID- 27045493
TI  - Evaluation and Testing of Junctional Tourniquets by Special Operation Forces
      Personnel: A Comparison of the Combat Ready Clamp and the Junctional Emergency
      Treatment Tool.
AB  - BACKGROUND: Previous research has shown that external hemorrhage from proximal
      leg amputations and junctional sites represents 19.2% of potentially survivable
      lethal hemorrhage. A recent effort to address this problem has resulted in the
      development of various junctional tourniquets. This study assessed and compared
      two Tactical Combat Casualty Care Committee-approved junctional tourniquets, the
      Combat Ready Clamp (CRoC) and the Junctional Emergency Treatment Tool (JETT), to
      contribute to their future development and to better inform on the decisions for
      device selection by military units. Aims of the study also were to provide
      concrete feedback and suggestions on how to effectively apply the devices.
      METHODS: Via a specific questionnaire, 75 international attendees of the
      International Special Training Centre Medical Branch Special Operations Forces
      Advanced Medical First Responder course evaluated the CRoC and the JETT on
      different parameters. Both devices were tested objectively through timed
      applications aimed at stopping unilateral lower-extremity distal pulse on 33 of
      these 75 students, verified by palpation by Medical Branch instructors.
      Subjective and objective data were examined for mutual correlation. RESULTS:
      Users ranked the JETT higher than the CRoC on all parameters, including
      effectiveness on the battlefield (rho < .001), ease of use (rho < .039), speed of
      application (rho < .001), and not slipping in use (rho < .001), although the
      difference on other parameters such as effectiveness in hemorrhage control was
      not statistically significant. Considering all parameters together, the JETT was
      evaluated as a better device than the CRoC (rho < .001). The application time
      measurement suggested that the JETT was applied faster (by approximately 15
      seconds on average; rho < .001). The fastest CRoC and JETT applications were 37
      and 29 seconds, respectively. The JETT was not easier to use or more effective
      than the CRoC; there was a 9% failure rate of the JETT occluding a unilateral
      common femoral artery. The JETT's efficacy in occluding a unilateral common
      femoral artery can be compromised if the device's pelvic binder is not
      sufficiently tightened prior to threading the T-handled pad. The CRoC's
      application time can be drastically reduced if the device is kept assembled and
      firm pressure is immediately asserted upon placement on the intended location
      through the vertical arm, then threading the device. Both devices were applied
      safely; no adverse effects were reported during or after application. CONCLUSION:
      Even though the JETT might be preferred by military medical providers, the CRoC
      still has merits. As both devices proved to occlude the arterial flow in no less
      than 54 seconds on average, they could be used to supplement direct pressure and
      wound packing, the latter two still being considered the immediate actions for
      inguinal bleeding control. Considering that the CRoC and the JETT can be applied
      in as little as 37 and 29 seconds, respectively, users should be effectively
      trained and entirely proficient on either device to justify their election as the
      primary countermeasure to hemorrhage not amenable to regular tourniquets.

PMID- 27045494
TI  - Accuracy and Reliability of Triage at the Point of Injury During Operation
      Enduring Freedom.
AB  - BACKGROUND: Accurate point-of-injury reports and casualty evacuation requests
      allow for optimal resource utilization. However, the accuracy of these reports
      has not been previously studied. METHODS: All trauma patients treated at one of
      three forward surgical elements (FSE) in Western Afghanistan during May-August
      2012 were prospectively included. North American Treaty Organization (NATO) 9
      line medical evacuation request and mechanism, injuries, signs, and treatments
      (MIST) reports were compared to the initial findings on arrival to the FSE.
      RESULTS: There were 179 casualty evacuation reports and 298 patients. NATO 9-line
      and/or MIST reports were available for 70% of these. Triage was accurate for 77%,
      but there was 17% overtriage and 6% undertriage (k = .619). The number of
      patients was accurate in 95% of reports, the mechanism of injury was accurate for
      98%, and the body region involved was accurate for 92% (k = .850, .943, and .870,
      respectively). There was no difference between the mean vital signs at the point
      of injury or on arrival at the FSE. When analyzed individually, however, there
      was no correlation between each casualty's pulse, mean arterial pressure, or
      respiratory rate between the two time points. DISCUSSION: There was a high degree
      of correlation between the triage category of casualty evacuation reports and the
      patient's actual medical needs. There was also a highly significant association
      with the number of patients, mechanism of injury, and bodily injuries. However,
      there was discordance between the vital signs at an individual level, which may
      represent regression toward the resuscitation threshold.

PMID- 27045495
TI  - SOLCUS: Update On Point-of-Care Ultrasound In Special Operations Medicine.
AB  - Point-of-care ultrasonography has been recognized as a relevant and versatile
      tool in Special Operations Forces (SOF) medicine. The Special Operator Level
      Clinical Ultrasound (SOLCUS) program has been developed specifically for SOF
      Medics. A number of challenges, including skill sustainment, high-volume
      training, and quality assurance, have been identified. Potential solutions,
      including changes to content delivery methods and application of tele-ultrasound,
      are described in this article. Given the shift in operational context toward
      extended care in austere environments, a curriculum adjustment for the SOLCUS
      program is also proposed. 

PMID- 27045496
TI  - SOLCUS After-Action Report: From Good Idea to the Largest Ultrasound Training
      Program in the Department of Defense.

PMID- 27045497
TI  - USASOC Division Of Science & Technology: What It Means For Special Operations
      Medicine.

PMID- 27045498
TI  - Traumatic Brain Injury: Its Outcomes and High Altitude.

PMID- 27045499
TI  - Power To The People.

PMID- 27045500
TI  - Needle Decompression.

PMID- 27045501
TI  - Red Rash.
AB  - The series objective is to review various clinical conditions/ presentations,
      including the latest evidence on management, and to dispel common myths. In the
      process, core knowledge and management principles are enhanced. A clinical case
      will be presented. Cases will be drawn from real life but phrased in a context
      that is applicable to the Special Operations Forces (SOF) or tactical emergency
      medical support (TEMS) environment. Details will be presented in such a way that
      the reader can follow along and identify how they would manage the case
      clinically depending on their experience and environment situation. Commentary
      will be provided by currently serving military medical technicians. The medics
      and author will draw on their SOF experience to communicate relevant clinical
      concepts pertinent to different operational environments including SOF and TEMS.
      Commentary and input from active special operations medical technicians will be
      part of the feature. 

PMID- 27045502
TI  - Sleep As A Strategy For Optimizing Performance.
AB  - Recovery is an essential component of maintaining, sustaining, and optimizing
      cognitive and physical performance during and after demanding training and
      strenuous missions. Getting sufficient amounts of rest and sleep is key to
      recovery. This article focuses on sleep and discusses (1) why getting sufficient
      sleep is important, (2) how to optimize sleep, and (3) tools available to help
      maximize sleep-related performance. Insufficient sleep negatively impacts safety
      and readiness through reduced cognitive function, more accidents, and increased
      military friendly-fire incidents. Sufficient sleep is linked to better cognitive
      performance outcomes, increased vigor, and better physical and athletic
      performance as well as improved emotional and social functioning. Because Special
      Operations missions do not always allow for optimal rest or sleep, the impact of
      reduced rest and sleep on readiness and mission success should be minimized
      through appropriate preparation and planning. Preparation includes periods of
      "banking" or extending sleep opportunities before periods of loss, monitoring
      sleep by using tools like actigraphy to measure sleep and activity, assessing
      mental effectiveness, exploiting strategic sleep opportunities, and consuming
      caffeine at recommended doses to reduce fatigue during periods of loss. Together,
      these efforts may decrease the impact of sleep loss on mission and performance. 

PMID- 27045503
TI  - Zika Virus.

PMID- 27045504
TI  - Injuries And Footwear (Part 2): Minimalist Running Shoes.
AB  - This article defines minimalist running shoes and examines physiological,
      biomechanical, and injury rate differences when running in conventional versus
      minimalist running shoes. A minimalist shoe is one that provides "minimal
      interference with the natural movement of the foot, because of its high
      flexibility, low heel to toe drop, weight and stack height, and the absence of
      motion control and stability devices." Most studies indicate that running in
      minimalist shoes results in a lower physiological energy cost than running in
      conventional shoes, likely because of the lower weight of the minimalist shoe.
      Most individuals running in conventional shoes impact the ground heel first
      (rearfoot strike pattern), whereas most people running in minimalist shoes tend
      to strike with the front of the foot (forefoot strike pattern). The rate at which
      force is developed on ground impact (i.e., the loading rate) is generally higher
      when running in conventional versus minimalist shoes. Findings from studies that
      have looked at associations between injuries and foot strike patterns or injuries
      and loading rates are conflicting, so it is not clear if these factors influence
      injury rates; more research is needed. Better-designed prospective studies
      indicate that bone stress injuries and the overall injury incidence are higher in
      minimalist shoes during the early weeks (10-12 weeks) of transition to this type
      of footwear. Longer-term studies are needed to define injury rates once runners
      are fully transitioned to minimalist shoes. At least one longer-term minimalist
      shoe investigation is ongoing and, hopefully, will be published soon. 

PMID- 27045505
TI  - A Threat-based, Statewide EMS Protocol To Address Lifesaving Interventions In
      Potentially Volatile Environments.

PMID- 27045506
TI  - Experience Of A US Air Force Surgical And Critical Care Team Deployed In Support
      Of Special Operations Command Africa.
AB  - An eight-person team of conventional US Air Force (USAF) medical providers
      deployed to support US Special Operations Forces (SOF) in North and West Africa
      for the first time in November 2014. The predeployment training, operations while
      deployed, and lessons learned from the challenges of performing surgery and
      medical evacuations in the remote desert environment of Chad and Niger on the
      continent of Africa are described. The vast area of operations and far-forward
      posture of these teams requires cooperation between partner African nations, the
      French military, and SOF to make these medical teams effective providers of
      surgical and critical care in Africa. The continuous deployment of conventional
      USAF medical providers since 2014 in support of US Special Operations Command
      Africa is challenging and will benefit from more medical teams and effective air
      assets to provide casualty evacuation across the vast area of operations. 

PMID- 27045507
TI  - All That Swells Is Not A Bruise The Morel-Lavallee Lesion.
AB  - Frequently overlooked, Morel-Lavallee lesions are associated with a closed
      degloving or shearing mechanism causing a dehiscence of underlying soft tissue
      with formation of a potential space. This space fills with blood, lymph, and
      cellular debris, giving the lesion a fluctuant appearance on examination. The
      potential space associated with larger lesions can be a source for hemorrhage in
      the appropriate clinical context. However, these lesions are often diagnosed late
      in their clinical course or are misdiagnosed, leading to long-term complications.
      Management of this injury typically depends upon the size of the lesion. This
      article discusses a Morel-Lavallee lesion in an active-duty Servicemember
      requiring treatment by a plastic surgeon and includes the pathophysiology of
      Morel-Lavallee lesions, diagnostic strategies, and management pearls. 

PMID- 27045508
TI  - Prolonged Field Care Working Group Fluid Therapy Recommendations.
AB  - The Prolonged Field Care Working Group concurs that fresh whole blood (FWB) is
      the fluid of choice for patients in hemorrhagic shock, and the capability to
      transfuse FWB should be a basic skill set for Special Operations Forces (SOF)
      Medics. Prolonged field care (PFC) must also address resuscitative and
      maintenance fluid requirements in nonhemorrhagic conditions. 

PMID- 27045509
TI  - Closing The Gap: Improving Trauma Care On The Ukrainian Battlefield.
AB  - Since early 2014, Ukraine has been involved in a violent social and political
      revolution that has taken more than 7,000 lives. Many of these deaths were due to
      limited field medical care and prolonged evacuation times because the Ukrainian
      military has been slow to adopt standard combat medical processes. We deployed
      with the US Army's 173rd Airborne Brigade to train soldiers in the National Guard
      of Ukraine (NGU) on combat first aid. We discovered that a major deficiency
      limiting the quality of trauma care and evacuation is an endemic lack of prior
      coordination and planning. The responsibility for this coordination falls on
      military leaders; therefore, we delivered medical operations training to officers
      of the NGU unit and observed great improvement in medical care sustainment. We
      recommend systematic leader education in best medical practices be
      institutionalized at all levels of the Ukrainian Army to foster sustained
      improvement and refinement of trauma care. 

PMID- 27045510
TI  - Progress Of Tactical Emergency Medical Support In Japan.

PMID- 27045511
TI  - Protruding Features of Viral Capsids Are Clustered on Icosahedral Great Circles.
AB  - Spherical viruses are remarkably well characterized by the Triangulation (T)
      number developed by Casper and Klug. The T-number specifies how many viral capsid
      proteins are required to cover the virus, as well as how they are further
      subdivided into pentamer and hexamer subunits. The T-number however does not
      constrain the orientations of these proteins within the subunits or dictate where
      the proteins should place their protruding features. These protrusions often take
      the form of loops, spires and helices, and are significant because they aid in
      stability of the capsid as well as recognition by the host organism. Until now
      there has be no overall understanding of the placement of protrusions for
      spherical viruses, other than they have icosahedral symmetry. We constructed a
      set of gauge points based upon the work affine extensions of Keef and Twarock,
      which have fixed relative angular locations with which to measure the locations
      of these features. This work adds a new element to our understanding of the
      geometric arrangement of spherical viral capsid proteins; chiefly that the
      locations of protruding features are not found stochastically distributed in an
      icosahedral manner across the viral surface, but instead these features are found
      only in specific locations along the 15 icosahedral great circles. We have found
      that this result holds true as the T number and viral capsids size increases,
      suggesting an underlying geometric constraint on their locations. This is in
      spite of the fact that the constraints on the pentamers and hexamer orientations
      change as a function of T-number, as you need to accommodate more hexamers in the
      same solid angle between pentamers. The existence of this angular constraint of
      viral capsids suggests that there is a fitness or energetic benefit to the virus
      placing its protrusions in this manner. This discovery may have profound impacts
      on identifying and eliminating viral pathogens, understanding evolutionary
      constraints as well as bioengineering for capsid drug delivery systems. This
      result also suggests that in addition to biochemical attachment restrictions,
      there are additional geometric constraints that should be adhered to when
      modifying protein capsids. 

PMID- 27045512
TI  - Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin
      and B-cell lymphomas.
AB  - Activation of the programmed death 1 (PD1)/PD1 ligand (PDL1) pathway is important
      for tumor cells to escape from immune control. The clinical efficacy of
      therapeutic modulation of the PD1-PDL1 pathway has been recently shown in
      classical Hodgkin lymphoma (cHL), but little is known about the frequency and
      diagnostic and prognostic importance of PDL1 expression in lymphomas. The
      available anti-PDL1 antibody clones E1L3N and SP142 were compared, and a large
      cohort of Hodgkin lymphomas (n=280) and B-cell lymphomas (n=619) was examined for
      PDL1 using E1L3N. The results were correlated with the expression of other
      phenotypic markers, interphase fluorescence in situ hybridization data of the
      9p24.1 region (PDL1 locus), and the clinical outcome. PDL1 was expressed on more
      than 5% of tumor cells in 70% of cHL, 54% of nodular lymphocyte-predominant
      Hodgkin lymphoma, and 35% of primary mediastinal B-cell lymphomas; in the latter,
      PDL1 expression correlated with PDL1 gains (rho=0.573). PDL1 was expressed in 31%
      of primary diffuse large B-cell lymphomas (DLBCLs), whereas most other entities
      did not express PDL1. In cHL, expression of PDL1 correlated with increased
      numbers of granzyme+ T cells (rho=0.251) and CD68+ macrophages (rho=0.221) but
      with decreased numbers of FoxP3+ T cells (rho=0.145). In activated B-cell-like
      DLBCL, PDL1 positively correlated with PD1+ T cells, whereas an inverse
      correlation with FoxP3+ T cells was seen in the germinal center B-cell-like
      DLBCL. PDL1 expression can be diagnostically valuable in some gray zones around
      DLBCL and cHL; it identifies an "immune escape" cluster of cHL and activated B
      cell-like DLBCL with increased granzyme+ and PD1+ T cells and macrophages and
      decreased regulatory T cells.

PMID- 27045513
TI  - Histologic analysis of eosinophils and mast cells of the gastrointestinal tract
      in healthy Canadian children.
AB  - Many gastrointestinal (GI) disorders, including GI eosinophilia and inflammatory
      bowel disease, can be characterized by increased mucosal eosinophils (EOs) or
      mast cells (MCs). Normal mucosal cellular counts along the GI tract in healthy
      children have not been established for a Canadian pediatric population. To
      establish a benchmark reference, we quantified EO and MC from 356 mucosal
      biopsies of the GI tract obtained during upper and lower endoscopic biopsies of
      38 pediatric patients in eastern Ontario. Mean total counts of EO varied for the
      11 tissues we examined, from a low of 7.6+/-6.5/high-power field (HPF) (*40
      [*400, 0.55mm(2)]) in the body of the stomach to a high of 50.3+/-17.4/HPF in the
      cecum. The lower GI tract (ileum, cecum, colon, sigmoid, and rectum) generally
      had higher total EO counts than the upper GI tract (antrum and body of stomach,
      duodenum, and duodenal cap) (combined average of 32.1+/-20.6 versus 19.3+/-15.8,
      respectively). Similarly, the number of mucosal MC was different in the various
      regions of the GI tract ranging from 0.04+/-0.2/HPF in the duodenal cap to 0.9+/
      2.6/HPF in the ileum. Total counts for EO and MC in the lamina propria were not
      significantly different between sexes when adjusted for multiple testing. EO
      polarity was absent in many cases, irrespective of the GI region. These
      numeration and localization of EO and MC will provide normative data for upper
      and lower endoscopic GI biopsies in the pediatric population of Eastern Ontario.

PMID- 27045514
TI  - Expression of Napsin A is common in Arias-Stella reaction.

PMID- 27045515
TI  - Utility of a novel triple marker (combination of thyroid transcription factor 1,
      Napsin A, and P40) in the subclassification of non-small cell lung carcinomas
      using fine-needle aspiration cases.
AB  - Personalized treatment of lung cancer requires an accurate subclassification of
      non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC), squamous cell
      carcinoma (SqCC), and other subtypes. In poorly differentiated tumors especially
      on small fine-needle aspirate specimens, the subclassification could be difficult
      in certain cases. Our previous study using resected tumor tissue has shown that
      the combination of commonly used individual markers (thyroid transcription factor
      1 [TTF-1], P40, and Napsin A) into a novel triple marker has high sensitivity and
      specificity in subclassification of NSCLC and also the advantage of using minimal
      tumor tissue. In this study, we further evaluated the utility of this novel
      triple marker using fine-needle aspirate cases. We included primary NSCLC,
      consisting of 37 SqCCs (primary, 35; metastasis, 2) and 50 ADCs (primary, 29;
      metastasis, 21), 12 metastatic ADCs of nonpulmonary primary, and 10 small cell
      lung carcinomas. The immunohistochemical patterns were semiquantitatively scored.
      In lung SqCCs and ADCs, the sensitivity and specificity of the triple marker were
      100% and 97.1% and 86.0% and 100%, respectively. The triple marker showed no
      immunoreactivity in 12 metastatic nonpulmonary ADCs. In 10 small cell lung
      carcinomas, TTF-1 had focal positivity in 40% of cases. The limitations of the
      triple marker include staining of alveolar macrophages (by TTF-1 and Napsin A),
      basal layer of bronchial epithelial cells (by P40), and nonspecific cytoplasmic
      staining of TTF-1. Our study not only supports our previous finding using
      resected tumor specimens but also provides evidence that the triple marker can be
      used for cytological material and preserving tumor tissue for molecular testing.

PMID- 27045516
TI  - The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate
      Affinity, Inhibition and Regulation.
AB  - The combination of passive drug permeability, affinity for uptake and efflux
      transporters as well as gastrointestinal metabolism defines net drug absorption.
      Efflux mechanisms are often overlooked when examining the absorption phase of
      drug bioavailability. Knowing the affinity of antimalarials for efflux
      transporters such as P-glycoprotein (P-gp) may assist in the determination of
      drug absorption and pharmacokinetic drug interactions during oral absorption in
      drug combination therapies. Concurrent administration of P-gp inhibitors and P-gp
      substrate drugs may also result in alterations in the bioavailability of some
      antimalarials. In-vitro Caco-2 cell monolayers were used here as a model for
      potential drug absorption related problems and P-gp mediated transport of drugs.
      Artemisone had the highest permeability at around 50 x 10(-6) cm/sec, followed by
      amodiaquine around 20 x 10(-6) cm/sec; both mefloquine and artesunate were around
      10 x 10(-6) cm/sec. Methylene blue was between 2 and 6 x 10(-6) cm/sec depending
      on the direction of transport. This 3 fold difference was able to be halved by
      use of P-gp inhibition. MRP inhibition also assisted the consolidation of the
      methylene blue transport. Mefloquine was shown to be a P-gp inhibitor affecting
      our P-gp substrate, Rhodamine 123, although none of the other drugs impacted upon
      rhodamine123 transport rates. In conclusion, mefloquine is a P-gp inhibitor and
      methylene blue is a partial substrate; methylene blue may have increased
      absorption if co-administered with such P-gp inhibitors. An upregulation of P-gp
      was observed when artemisone and dihydroartemisinin were co-incubated with
      mefloquine and amodiaquine.

PMID- 27045517
TI  - Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of
      Bacterial Mutants.
AB  - Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical) are
      thought to contribute to the rapid bactericidal activity of diverse antimicrobial
      agents. The possibility has been raised that consumption of antioxidants in food
      may interfere with the lethal action of antimicrobials. Whether nutritional
      supplements containing antioxidant activity are also likely to interfere with
      antimicrobial lethality is unknown. To examine this possibility, resveratrol, a
      popular antioxidant dietary supplement, was added to cultures of Escherichia coli
      and Staphylococcus aureus that were then treated with antimicrobial and assayed
      for bacterial survival and the recovery of mutants resistant to an unrelated
      antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present
      during human consumption, caused a 2- to 3-fold reduction in killing during a 2
      hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory
      concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders
      of magnitude. Resveratrol also reduced the increase in reactive oxygen species
      (ROS) characteristic of treatment with quinolone (oxolinic acid). These data
      support the general idea that the lethal activity of some antimicrobials involves
      ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6
      fold) the recovery of rifampicin-resistant mutants arising from the action of
      ciprofloxacin, kanamycin, or daptomycin. This result is consistent with
      resveratrol reducing ROS to sublethal levels that are still mutagenic, while the
      absence of resveratrol allows ROS levels to high enough to kill mutagenized
      cells. Suppression of antimicrobial lethality and promotion of mutant recovery by
      resveratrol suggests that the antioxidant may contribute to the emergence of
      resistance to several antimicrobials, especially if new derivatives and/or
      formulations of resveratrol markedly increase bioavailability. 

PMID- 27045518
TI  - Bacterial Community Responses to Soils along a Latitudinal and Vegetation
      Gradient on the Loess Plateau, China.
AB  - Soil bacterial communities play an important role in nutrient recycling and
      storage in terrestrial ecosystems. Loess soils are one of the most important soil
      resources for maintaining the stability of vegetation ecosystems and are mainly
      distributed in northwest China. Estimating the distributions and affecting
      factors of soil bacterial communities associated with various types of vegetation
      will inform our understanding of the effect of vegetation restoration and climate
      change on these processes. In this study, we collected soil samples from 15 sites
      from north to south on the Loess Plateau of China that represent different
      ecosystem types and analyzed the distributions of soil bacterial communities by
      high-throughput 454 pyrosequencing. The results showed that the 142444 sequences
      were grouped into 36816 operational taxonomic units (OTUs) based on 97%
      similarity. The results of the analysis showed that the dominant taxonomic phyla
      observed in all samples were Actinobacteria, Proteobacteria, Chloroflexi,
      Acidobacteria and Planctomycetes. Actinobacteria and Proteobacteria were the two
      most abundant groups in all samples. The relative abundance of Actinobacteria
      increased from 14.73% to 40.22% as the ecosystem changed from forest to sandy,
      while the relative abundance of Proteobacteria decreased from 35.35% to 21.40%.
      Actinobacteria and Proteobacteria had significant correlations with mean annual
      precipitation (MAP), pH, and soil moisture and nutrients. MAP was significantly
      correlated with soil chemical and physical properties. The relative abundance of
      Actinobacteria, Proteobacteria and Planctomycetes correlated significantly with
      MAP, suggesting that MAP was a key factor that affected the soil bacterial
      community composition. However, along with the MAP gradient, Chloroflexi,
      Bacteroidetes and Cyanobacteria had narrow ranges that did not significantly vary
      with the soil and environmental factors. Overall, we conclude that the edaphic
      properties and/or vegetation types are driving bacterial community composition.
      MAP was a key factor that affects the composition of the soil bacteria on the
      Loess Plateau of China. 

PMID- 27045519
TI  - Anemia Management in the China Dialysis Outcomes and Practice Patterns Study.
AB  - BACKGROUND: As the utilization of hemodialysis increases in China, it is critical
      to examine anemia management. METHODS: Using data from the China Dialysis
      Outcomes and Practice Patterns Study (DOPPS), we describe hemoglobin (Hgb)
      distribution and anemia-related therapies. RESULTS: Twenty one percent of China's
      DOPPS patients had Hgb <9 g/dl, compared with <=10% in Japan and North America. A
      majority of medical directors targeted Hgb >=11. Patients who were female,
      younger, or recently hospitalized had higher odds of Hgb <9; those with insurance
      coverage or on twice weekly dialysis had lower odds of Hgb <9. Iron use and
      erythropoietin-stimulating agents (ESAs) dose were modestly higher for patients
      with Hgb <9 compared with Hgb in the range 10-12. CONCLUSION: A large proportion
      of hemodialysis patients in China's DOPPS do not meet the expressed Hgb targets.
      Less frequent hemodialysis, patient financial contribution, and lack of a
      substantial increase in ESA dose at lower Hgb concentrations may partially
      explain this gap. Video Journal Club 'Cappuccino with Claudio Ronco' at
      http://www.karger.com/?doi=442741.

PMID- 27045520
TI  - Motivational interviewing to enhance adolescent mental health treatment
      engagement: a randomized clinical trial.
AB  - BACKGROUND: The prevalence of anxiety and mood disorders in adolescents is a
      growing public health concern worldwide. Given the high rates of drop-out and
      limited resources available in psychiatric settings, the importance of engaging
      adolescents in evidence-based treatments cannot be understated. The aim of the
      study was to determine the efficacy of motivational interviewing (MI), as a brief
      pre-treatment intervention, to enhance treatment engagement in a standard therapy
      setting (group cognitive behavioral therapy; gCBT) for adolescents with anxiety
      and mood disorders. METHOD: Ninety-six adolescents (13-18 years) with a principal
      diagnosis of an anxiety or mood disorder participated in a trial conducted at two
      publicly funded outpatient services. Participants were randomly assigned to
      individual MI for treatment engagement prior to gCBT (MI + gCBT), or to an
      individually administered active control (befriending) prior to gCBT (befriending
      + gCBT). Eight pairs of gCBT were run in parallel. Outcome measures were the mean
      number of gCBT sessions attended, treatment initiation, and ratings of readiness
      for treatment. RESULTS: Participants randomized to MI as a pretreatment
      intervention attended significantly more group therapy sessions compared to those
      in the active control condition. The MI group also demonstrated greater treatment
      initiation, and ratings of treatment readiness were significantly higher for
      those randomized to MI. CONCLUSIONS: MI, used as a pre-treatment intervention,
      enhanced group treatment engagement in adolescents diagnosed with anxiety and
      mood disorders compared to the active control condition. MI is a promising
      intervention to facilitate engagement in adolescent mental health settings.

PMID- 27045521
TI  - Undibacterium arcticum sp. nov., isolated from arctic alpine soil.
AB  - A Gram-stain-negative, aerobic, motile rod-shaped bacterium, designated 6-67T,
      was isolated from a soil sample collected from Longyearbyen, Svalbard. Its
      taxonomic position was investigated by genotypic, phenotypic and chemotaxonomic
      analyses. This isolate grew at 4-28  degrees C (optimum, 20  degrees C), at pH
      5.0-9.0 (optimum, pH 7.0) and with 0-0.2 % (w/v) NaCl. Strain 6-67T contained Q-8
      as a major respiratory quinone and MK-7 as a minor component; the major fatty
      acids were summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and C16 : 0.
      The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, two unidentified phospholipids and one unidentified
      aminophospholipid. The polyamines were putrescine and 2-hydroxyputrescine. 16S
      rRNA gene sequence analysis indicated that the novel strain 6-67T belonged to the
      family Oxalobacteraceae within the class Betaproteobacteria. The DNA G+C content
      of strain 6-67T was 56.21 mol%. On the basis of phylogenetic, physiological and
      chemotaxonomic data, strain 6-67T is considered to represent a novel species of
      the genus Undibacterium, for which the name Undibacterium arcticum sp. nov. is
      proposed. The type strain is 6-67T (=CCTCC AB 2015162T=KCTC 42986T). 

PMID- 27045523
TI  - Evaluating the effectiveness of localized control strategies to curtail
      chikungunya.
AB  - Chikungunya, a re-emerging arbovirus transmitted to humans by Aedes aegypti and
      Ae. albopictus mosquitoes, causes debilitating disease characterized by an acute
      febrile phase and chronic joint pain. Chikungunya has recently spread to the
      island of St. Martin and subsequently throughout the Americas. The disease is now
      affecting 42 countries and territories throughout the Americas. While chikungunya
      is mainly a tropical disease, the recent introduction and subsequent spread of
      Ae. albopictus into temperate regions has increased the threat of chikungunya
      outbreaks beyond the tropics. Given that there are currently no vaccines or
      treatments for chikungunya, vector control remains the primary measure to curtail
      transmission. To investigate the effectiveness of a containment strategy that
      combines disease surveillance, localized vector control and transmission
      reduction measures, we developed a model of chikungunya transmission dynamics
      within a large residential neighborhood, explicitly accounting for human and
      mosquito movement. Our findings indicate that prompt targeted vector control
      efforts combined with measures to reduce transmission from symptomatic cases to
      mosquitoes may be highly effective approaches for controlling outbreaks of
      chikungunya, provided that sufficient detection of chikungunya cases can be
      achieved. 

PMID- 27045524
TI  - Pain facilitation and pain inhibition during conditioned pain modulation in
      fibromyalgia and in healthy controls.
AB  - Although fibromyalgia (FM) is associated with a deficit in inhibitory conditioned
      pain modulation (CPM), the discriminative power of CPM procedures is unknown.
      Moreover, the high intersubject heterogeneity in CPM responses in FM raises the
      possibility that a sizeable subgroup of these patients may experience pain
      facilitation during CPM, but the phenomenon has not been explicitly studied. To
      address these issues, 96 patients with FM and 71 healthy controls were recruited.
      Thermal stimuli were used to measure pain thresholds. Pain inhibition was
      elicited using a tonic thermal test (Peltier thermode) administered before and
      after activation of CPM mechanisms using a cold pressor test. Thermal pain
      thresholds were lower in patients with FM than in healthy controls. Pain ratings
      during the cold pressor test were higher in patients with FM, relative to
      controls. The CPM inhibitory efficacy was lower in patients with FM than in
      controls. The CPM procedure had good specificity (78.9%) but low sensitivity
      (45.7%), whereas a composite pain index had good sensitivity (75.0%) and
      specificity (78.9%). Finally, the rate of patients with FM who reported pain
      facilitation during the CPM procedure was found to be significantly increased
      compared with that of controls (41.7% vs 21.2%). The good discriminative power of
      the composite pain index highlights the need for further validation studies using
      mechanistically relevant psychophysical procedures in FM. The low sensitivity of
      the CPM procedure, combined with the large proportion of patients with FM
      experiencing pain facilitation during CPM, strongly suggests that endogenous pain
      inhibition mechanisms are deeply impaired in patients with FM, but only in a
      subgroup of them.

PMID- 27045525
TI  - ASK1 signalling regulates brown and beige adipocyte function.
AB  - Recent studies suggest that adult humans have active brown or beige adipocytes,
      the activation of which might be a therapeutic strategy for the treatment of
      diverse metabolic diseases. Here we show that the protein kinase ASK1 regulates
      brown and beige adipocytes function. In brown or white adipocytes, the PKA-ASK1
      p38 axis is activated in response to cAMP signalling and contributes to the cell
      autonomous induction of genes, including Ucp1. Global and fat-specific ASK1
      deficiency leads to impaired metabolic responses, including thermogenesis and
      oxygen consumption, at the cell and whole-body levels, respectively. Our data
      thus indicate that the ASK1 signalling axis is a regulator of brown and beige
      adipocyte gene expression and function. 

PMID- 27045526
TI  - A label-free and enzyme-free ultra-sensitive transcription factors biosensor
      using DNA-templated copper nanoparticles as fluorescent indicator and hairpin DNA
      cascade reaction as signal amplifier.
AB  - Detection and quantification of specific protein with ultralow concentration play
      a crucial role in biotechnological applications and biomedical diagnostics. In
      this paper, a label-free and enzyme-free amplified fluorescent biosensor has been
      developed for transcription factors detection based on AT-rich double-stranded
      DNA-templated copper nanoparticles (ds DNA/Cu NPs) and hairpin DNA cascade
      reaction. This strategy was demonstrated by using nuclear factor-kappa B p50 (NF
      kappaB p50) and specific recognition sequences as a model case. In this assay, a
      triplex consists of double-stranded DNA containing NF-kappaB p50 specifically
      binding sequences and a special design single-stranded DNA (Trigger) which is
      able to activate the hairpin DNA cascade amplifier (HDCA). In the presence of NF
      kappaB p50, the triplex became unstable since the target bound to the recognition
      sequences with strong affinity. The selective binding event confirmed that the
      Trigger was successfully released from the triplex and initiated HDCA to yield
      the product which could effectively template the formation of fluorescent Cu NPs.
      The experimental results revealed that the advanced strategy was ultra-sensitive
      for detecting NF-kappaB p50 in the concentration range from 0.1 to 1000 pM with a
      detection limit of 0.096 pM. In addition, the relative standard deviation was
      4.08% in 3 repetitive assays of 500 pM NF-kappaB p50, which indicated that the
      reproducibility of this strategy was acceptable. Besides desirable sensitivity,
      the developed biosensor also showed high selectivity, cost-effective, and
      simplified operations. In addition, the proposed biosensing platform is
      versatile. By conjugating with various specific recognition units, it could hold
      considerable potential to sensitive and selective detect various DNA-binding
      proteins and might find wide applications in biomedical fields. 

PMID- 27045527
TI  - Celebrating 25 years of viewpoints.

PMID- 27045528
TI  - Relationship between children's performance-based motor skills and child, parent,
      and teacher perceptions of children's motor abilities using self/informant-report
      questionnaires.
AB  - BACKGROUND: Occupational therapists often assess the motor skill performance of
      children referred to them as part of the assessment process. AIM: This study
      investigated whether children's, parents' and teachers' perceptions of children's
      motor skills using valid and reliable self/informant-report questionnaires were
      associated with and predictive of children's actual motor performance, as
      measured by a standardised performance-based motor skill assessment. METHODS:
      Fifty-five typically developing children (8-12 years of age), their parents and
      classroom teachers were recruited to participate in the study. The children
      completed the Physical Self-Description Questionnaire (PSDQ) and the Self
      Perception Profile for Children. The parents completed the Developmental Profile
      III (DP-III) and the Developmental Coordination Disorder Questionnaire, whereas
      the teachers completed the Developmental Coordination Disorder Questionnaire and
      the Teacher's Rating Scale of Child's Actual Behavior. Children's motor
      performance composite scores were determined using the Bruininks-Oseretsky Test
      of Motor Proficiency, Second Edition (BOT-2). Spearman's rho correlation
      coefficients were calculated to identify if significant correlations existed and
      multiple linear regression was used to identify whether self/informant report
      data were significant predictors of children's motor skill performance. RESULTS:
      The child self-report scores had the largest number of significant correlations
      with the BOT-2 composites. Regression analysis found that the parent report DP
      III Physical subscale was a significant predictor of the BOT-2 Manual
      Coordination composite and the child-report questionnaire PSDQ. Endurance
      subscale was a significant predictor of the BOT-2 Strength and Agility composite.
      CONCLUSION: The findings support the use of top-down assessment methods from a
      variety of sources when evaluating children's motor abilities.

PMID- 27045529
TI  - What are the limits of occupational therapy practice?

PMID- 27045530
TI  - Technology-based interventions were found to have evidence of effectiveness on a
      range of outcomes, including social problem solving and facial and emotional
      processing skills for individuals with autism spectrum disorders.

PMID- 27045531
TI  - Mixed evidence exists for Internet-based education and support interventions for
      caregivers of someone with a chronic health condition in enhancing wellbeing and
      decreasing stress.

PMID- 27045533
TI  - Persistent improvement of ejection fraction in patients with a cardiac
      resynchronisation therapy defibrillator correlates with fewer appropriate ICD
      interventions and lower mortality.
AB  - QUESTION UNDER STUDY: Cardiac resynchronisation therapy with defibrillator back
      up (CRT-D) is a well-established treatment option for selected heart failure
      patients. Left ventricular ejection fraction (LVEF), an important risk
      determinant of life-threatening arrhythmias, can substantially ameliorate with
      CRT. Our hypothesis was that patients with LVEF improvement to >40% have a lower
      arrhythmic risk and fewer appropriate defibrillator therapies beyond year one.
      METHODS: In this retrospective analysis, all 175 patients with CRT-D implanted
      from February 2000 to June 2011 and follow-up of >2 years were identified. Every
      available echocardiography recording was collected. LVEF measurements were
      grouped to baseline and yearly intervals (+/-6 months). All appropriate
      defibrillator therapies were considered events. RESULTS: Age at implant was 65 +/
      10 years, 86% were male, and 45% patients had ischemic cardiomyopathy. Follow-up
      was 5.5 +/- 2.6 years. LVEF at implant was 25 +/- 6%, increased to 34 +/- 12%
      after one year and remained stable thereafter. 39% (69) of patients experienced a
      sustained increase of LVEF to >=40%, 14% of them had tachyarrhythmic events
      (versus 42.5% in those without such increase). Independent predictors for
      increase were higher baseline LVEF (HR 1.08 (95%-CI 1.04-1.28) per 1% increase)
      and lack of amiodarone (HR 0.37, 95%-CI 0.16-0.84). With cut-off values of >40%,
      >45% and >50%, the study hypothesis was refuted in 7%, 2.5% and 5%, respectively.
      Cumulative 5-year survival was 95% in improvers versus 73% in non-improvers (p
      <0.001). CONCLUSION: After CRT-D implantation, mean LVEF increased to >40% in 1/3
      of patients. These patients experienced significantly fewer arrhythmias during
      long-term follow-up when compared to patients with persisting LVEF <40%.

PMID- 27045534
TI  - Correction to Melanin-Concentrating Hormone Receptor 1 Antagonists Lacking an
      Aliphatic Amine: Synthesis and Structure-Activity Relationships of Novel 1
      (Imidazo[1,2-a]pyridin-6-yl)pyridin-2(1H)-one Derivatives.

PMID- 27045535
TI  - [Anticancer drugs: Which prices for therapeutic innovations?].
AB  - The expanding knowledge of the biological mechanisms underlying tumor development
      made it possible the recent emergence of new therapeutic approaches that are
      considered as undoubtedly innovative. Yet, to define and to evaluate the
      magnitude of a drug innovation require an examination of its intrinsic drug
      properties, medical utility as well as its mode of emergence. Recently,
      international academic societies, such as ESMO and ASCO, have proposed practical
      tools that may help quantifying the medical value of a given innovation.
      Currently, the sustained flux of therapeutic innovations in oncology is
      associated with an unprecedented growth of costs, the actual determinants of
      which remain under debate, but raising the critical issue of drugs pricing, and
      their potential individual or societal "financial toxicity". 

PMID- 27045536
TI  - Closantel Suppresses Angiogenesis and Cancer Growth in Zebrafish Models.
AB  - Angiogenesis has emerged as an important therapeutic target in several major
      diseases, including cancer and age-related macular degeneration. The zebrafish
      offer the potential for high-throughput drug discovery in a whole vertebrate
      system. In this study, we have taken advantage of the transgenic Tg (fli1a:EGFP)
      zebrafish line to screen the U.S. Drug Collection Library and identified 11 old
      drugs with antiangiogenic activity, including Closantel, an FDA-approved broad
      spectrum salicylanilide antiparasitic drug for a variety of types of animals.
      Closantel was confirmed to have antiangiogenic activity in zebrafish with a half
      inhibitory concentration (IC50) at 1.69 MUM on the intersegmental vessels and
      1.45 MUM on the subintestinal vessels. Closantel also markedly suppressed cancer
      growth in zebrafish xenotransplanted with human lymphoma, cervical cancer,
      pancreatic cancer, and liver cancer cells, generally in a dose-dependent manner.
      These data reveal that Closantel has antiangiogenesis and anticancer effects and
      could be a potential drug candidate for animal and human cancer treatments.
      Further study is needed to clarify the mechanisms involved in the
      antiangiogenesis and anticancer effects of Closantel.

PMID- 27045537
TI  - Snapshot of the supports of communication used by patients at a French
      psychiatric hospital: a digital or social division?
AB  - BACKGROUND: The role of information and communications technology is becoming
      increasingly prevalent in daily life and in the organization of medical care: are
      some people being left out? AIMS: To evaluate access to and the uses of
      communication resources by psychiatric patients, focusing on the means of
      communication (e.g. mobile phones and computers), access and frequency of
      internet use. METHODS: A questionnaire was distributed, over a period of 1 week,
      to inpatients or day hospitalised patients aged over 12 years in all care units.
      RESULTS: Access to and the uses of modern communication resources were lower than
      in the general population. Among places and means of internet consultation, the
      personal computer was most often cited, but only by 34%, and the use of mobile
      phones is still not widespread. Finally, day hospitalised subjects, the elderly,
      or subjects being treated in the psychosis care sector use internet and
      technology the least. CONCLUSIONS: Some differences exist between this population
      with mental illness and the general population on the use of new communication
      technologies. The possibility of integrating these techniques in individualized
      psychiatric care requires prior equipment and/or updates.

PMID- 27045538
TI  - Higher Incidence of Psychiatrist-Diagnosed Depression in Taiwanese Female School
      Age Children and Adolescents with Type 1 Diabetes: A Nationwide, Population
      Based, Retrospective Cohort Study.
AB  - OBJECTIVES: The aim of this study was to investigate the risk of clinical
      depression associated with type 1 diabetes in female Taiwanese children and
      adolescents. METHODS: Using Taiwan's National Health Insurance Research Database,
      we identified 1373 female children and adolescents, aged 5-18 years, with type 1
      diabetes diagnosed between 2000 and 2007. A comparison cohort was assembled,
      which consisted of 20 patients without type 1 diabetes, based on frequency
      matching for age interval and index year for each patient with type 1 diabetes.
      Both groups were followed until a psychiatrist diagnosed depression or the end of
      the follow-up period, up to a maximum period of 5 years from the index date. A
      Poisson regression model was used to calculate incidence rate ratios (IRRs) for
      depression between the type 1 diabetes cohort and the comparison cohort. RESULTS:
      The incidence rate of depression in the type 1 diabetes cohort was 228.4 per
      100,000 person-years and that in the comparison cohort was 73.9 per 100,000
      person-years. The type 1 diabetes cohort showed a significantly higher incidence
      of depression compared with the comparison cohort (IRR of 3.09, p < 0.001).
      CONCLUSION: Findings from this nationwide, population-based, retrospective cohort
      study showed that the incidence of psychiatrist-diagnosed depression was
      significantly higher in female Taiwanese school-age children and adolescents with
      type 1 diabetes compared with those without the disease.

PMID- 27045539
TI  - A Systematic Study on the Influence of Electron-Acceptors in Phenanthrocarbazole
      Dye-Sensitized Solar Cells.
AB  - In this work, by conjugating 2-cyanoacrylic acid (CA), 4
      (benzo[c][1,2,5]thiadiazol-7-yl)benzoic acid (BTBA), 4-(7
      ethynylbenzo[c][1,2,5]thiadiazol-4-yl)benzoic acid (EBTBA), and 4-((7
      ethynylbenzo[c][1,2,5]thiadiazol-4-yl)ethynyl)benzoic acid (EBTEBA) to a binary
      electron-donor diphenylamine-phenanthrocarbazole (DPA-PC), we systematically
      investigate the impacts of electron-acceptors upon energy level, energy gap,
      light-harvesting ability, photovoltaic parameter, and cell stability of donor
      acceptor dyes in photoelectrochemical cells. In conjunction with an ionic liquid
      composite electrolyte, the DPA-PC dye with EBTEBA as electron-acceptor yields a
      high power conversion efficiency of 8% and an outstanding stability after a 1000
      h aging test under the soaking of full sunlight at 60  degrees C in a dye
      sensitized solar cell. Femtosecond fluorescence up-conversion measurements have
      suggested that energy relaxation and electron injection both occur to dye
      molecules in the nonequilibrium excited states. Moreover, the time constants of
      injecting electrons from dye molecules in the excited states to titania are very
      dispersive for over 1 order of magnitude, mainly owing to the broad energy
      distribution of excited states. 

PMID- 27045540
TI  - Simplified greywater treatment systems: Slow filters of sand and slate waste
      followed by granular activated carbon.
AB  - One of the main actions of sustainability that is applicable to residential,
      commercial, and public buildings is the rational use of water that contemplates
      the reuse of greywater as one of the main options for reducing the consumption of
      drinking water. Therefore, this research aimed to study the efficiencies of
      simplified treatments for greywater reuse using slow sand and slow slate waste
      filtration, both followed by granular activated carbon filters. The system
      monitoring was conducted over 28 weeks, using analyses of the following
      parameters: pH, turbidity, apparent color, biochemical oxygen demand (BOD),
      chemical oxygen demand (COD), surfactants, total coliforms, and thermotolerant
      coliforms. The system was run at two different filtration rates: 6 and 2
      m(3)/m(2)/day. Statistical analyses showed no significant differences in the
      majority of the results when filtration rate changed from 6 to 2 m(3)/m(2)/day.
      The average removal efficiencies with regard to the turbidity, apparent color,
      COD and BOD were 61, 54, 56, and 56%, respectively, for the sand filter, and 66,
      61, 60, and 51%, respectively, for the slate waste filter. Both systems showed
      good efficiencies in removing surfactants, around 70%, while the pH reached
      values of around 7.80. The average removal efficiencies of the total and
      thermotolerant coliforms were of 61 and 90%, respectively, for the sand filter,
      and 67 and 80%, respectively, for the slate waste filter. The statistical
      analysis found no significant differences between the responses of the two
      systems, which attest to the fact that the slate waste can be a substitute for
      sand. The maximum levels of efficiency were high, indicating the potential of the
      systems, and suggesting their optimization in order to achieve much higher
      average efficiencies. 

PMID- 27045541
TI  - Environmental assessment of pavement infrastructure: A systematic review.
AB  - Through a critical review and systematic analysis of pavement life cycle
      assessment (LCA) studies published over the past two decades, this study shows
      that the available information regarding the environmental impacts of pavement
      infrastructure is not sufficient to determine what pavement type is more
      environmentally sustainable. Limitations and uncertainties related to data,
      system boundary and functional unit definitions, consideration of use and
      maintenance phase impacts, are identified as the main reasons for inconsistency
      of reported results in pavement LCA studies. The study outcomes also highlight
      the need for advancement of knowledge pertaining to: (1) utilization of
      performance-adjusted functional units, (2) accurate estimation of use,
      maintenance, and end-of-life impacts, (3) incorporation of the dynamic and
      uncertain nature of pavement condition performance in impact assessment; (4)
      development of region-specific inventory data for impact estimation; and (5)
      consideration of a standard set of impact categories for comparison of
      environmental performance of different pavement types. Advancing the knowledge in
      these areas is critical in providing consistent and reliable results to inform
      decision-making toward more sustainable roadway infrastructure. 

PMID- 27045542
TI  - Pharmacokinetics and pharmacogenomics of beta-lactam-induced neutropenia.
AB  - AIM: Determine if individuals with beta-lactam induced neutropenia have
      polymorphisms that impair function of MRP4 or OAT1/OAT3. METHODS: Subjects with
      beta-lactam induced neutropenia were compared to controls for the presence of
      MRP4 and OAT1/OAT3 polymorphisms, estimated plasma trough concentrations and area
      under the curve. RESULTS: Subjects with a homozygous polymorphism at MRP4 3348 A
      to G were 5.3 times more likely to develop neutropenia (p = 0.171). No
      statistical differences were noted in pharmacokinetic parameters. Contingency
      analysis of children greater than 5 years of age showed neutropenia in subjects
      who were homozygous wild type at MRP4 3348 A to G was significantly associated
      with standard or high dosing (p = 0.03). CONCLUSION: MRP4 3348 A to G should be
      further studied for potential contribution to the development of beta-lactam
      induced neutropenia.

PMID- 27045544
TI  - External validation of an individual prognostic calculator after transarterial
      chemoembolization for hepatocellular carcinoma.

PMID- 27045543
TI  - Ultrasensitive microfluidic analysis of circulating exosomes using a
      nanostructured graphene oxide/polydopamine coating.
AB  - Exosomes are cell-derived nano-sized vesicles that have been recently recognized
      as new mediators for many cellular processes and potential biomarkers for non
      invasive disease diagnosis and the monitoring of treatment response. To better
      elucidate the biology and clinical value of exosomes, there is a pressing need
      for new analytical technologies capable of the efficient isolation and sensitive
      analysis of such small and molecularly diverse vesicles. Herein, we developed a
      microfluidic exosome analysis platform based on a new graphene oxide/polydopamine
      (GO/PDA) nano-interface. To the best of our best knowledge, we report for the
      first time, the GO-induced formation of a 3D nanoporous PDA surface coating
      enabled by the microfluidic layer-by-layer deposition of GO and PDA. It was
      demonstrated that this nanostructured GO/PDA interface greatly improves the
      efficiency of exosome immuno-capture, while at the same time effectively
      suppressing non-specific exosome adsorption. Based on this nano-interface, an
      ultrasensitive exosome ELISA assay was developed to afford a very low detection
      limit of 50 MUL(-1) with a 4 log dynamic range, which is substantially better
      than the existing methods. As a proof of concept for clinical applications, we
      adapted this platform to discriminate ovarian cancer patients from healthy
      controls by the quantitative detection of exosomes directly from 2 MUL plasma
      without sample processing. Thus, this platform could provide a useful tool to
      facilitate basic and clinical investigations of exosomes for non-invasive disease
      diagnosis and to aid precision treatment.

PMID- 27045545
TI  - Three-dimensional printing of the retina.
AB  - PURPOSE OF REVIEW: Biological three-dimensional printing has received a lot of
      media attention over recent years with advances made in printing cellular
      structures, including skin and heart tissue for transplantation. Although
      limitations exist in creating functioning organs with this method, the hope has
      been raised that creating a functional retina to cure blindness is within reach.
      The present review provides an update on the advances made toward this goal.
      RECENT FINDINGS: It has recently been shown that two types of retinal cells,
      retinal ganglion cells and glial cells, can be successfully printed using a
      piezoelectric inkjet printer. Importantly, the cells remained viable and did not
      change certain phenotypic features as a result of the printing process. In
      addition, recent advances in the creation of complex and viable three-dimensional
      cellular structures have been made. SUMMARY: Some first promising steps toward
      the creation of a functional retina have been taken. It now needs to be
      investigated whether recent findings can be extended to other cells of the
      retina, including those derived from human tissue, and if a complex and viable
      retinal structure can be created through three-dimensional printing.

PMID- 27045547
TI  - (68)Ga-Bivalent Polypegylated Styrylpyridine Conjugates for Imaging Abeta Plaques
      in Cerebral Amyloid Angiopathy.
AB  - Abeta plaques deposited on blood vessels are associated with cerebral amyloid
      angiopathy (CAA). In an effort to selectively map these Abeta plaques, we are
      reporting a new series of (68)Ga labeled styrylpyridine derivatives with high
      molecular weights. In vitro binding to Abeta plaques in post-mortem Alzheimer's
      disease (AD) brain tissue showed that these (68)Ga labeled bivalent
      styrylpyridines displayed good affinities and specificity (Ki < 30 nM). In vitro
      autoradiography using post-mortem AD brain sections showed specific binding of
      these (68)Ga complexes to Abeta plaques. Biodistribution studies in normal mice
      showed very low initial brain uptakes (<0.3% dose/g) indicating a low blood-brain
      barrier (BBB) penetration. The preliminary results suggest that (68)Ga labeled
      bivalent styrylpyridines may be promising candidates as PET imaging radiotracers
      for detecting CAA.

PMID- 27045548
TI  - Editorial: Issue 30.2.

PMID- 27045549
TI  - Proceedings of the 2016 Spring Meeting of the Society of British.
AB  - This meeting is being hosted by Royal Victoria Infirmary in Newcastle, 20-22
      April 2016 at The Sage, Gateshead. The full abstracts of the platform
      presentations are followed by the titles of those submissions accepted as
      posters. The order of abstracts is that of presentation. These papers are
      'published in advance of the meeting. If any papers are subsequently withdrawn or
      not read to the society, an addendum to this effect will be published in the next
      issue of the journal. 

PMID- 27045550
TI  - MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1
      expression.
AB  - BACKGROUND: Altered levels of urocortin 1 (Ucn1) in the centrally projecting
      Edinger-Westphal nucleus (EWcp) of depressed suicide attempters or completers
      mediate the brain's response to stress, while the mechanism regulating Ucn1
      expression is unknown. We tested the hypothesis that microRNAs (miRNAs), which
      are vital fine-tuners of gene expression during the brain's response to stress,
      have the capacity to modulate Ucn1 expression. METHODS: Computational analysis
      revealed that the Ucn1 3' untranslated region contained a conserved binding site
      for miR-326. We examined miR-326 and Ucn1 levels in the EWcp of depressed suicide
      completers. In addition, we evaluated miR-326 and Ucn1 levels in the serum and
      the EWcp of a chronic variable mild stress (CVMS) rat model of behavioural
      despair and after recovery from CVMS, respectively. Gain and loss of miR-326
      function experiments examined the regulation of Ucn1 by this miRNA in cultured
      midbrain neurons. RESULTS: We found reduced miR-326 levels concomitant with
      elevated Ucn1 levels in the EWcp of depressed suicide completers as well as in
      the EWcp of CVMS rats. In CVMS rats fully recovered from stress, both serum and
      EWcp miR-326 levels rebounded to nonstressed levels. While downregulation of miR
      326 levels in primary midbrain neurons enhanced Ucn1 expression levels, miR-326
      overexpression selectively reduced the levels of this neuropeptide. LIMITATIONS:
      This study lacked experiments showing that in vivo alteration of miR-326 levels
      alleviate depression-like behaviours. We show only correlative data for miR-325
      and cocaine- and amphetamine-regulated transcript levels in the EWcp. CONCLUSION:
      We identified miR-326 dysregulation in depressed suicide completers and
      characterized this miRNA as an upstream regulator of the Ucn1 neuropeptide
      expression in midbrain neurons.

PMID- 27045551
TI  - Partially restored resting-state functional connectivity in women recovered from
      anorexia nervosa.
AB  - BACKGROUND: We have previously shown increased resting-state functional
      connectivity (rsFC) in the frontoparietal network (FPN) and the default mode
      network (DMN) in patients with acute anorexia nervosa. Based on these findings we
      investigated within-network rsFC in patients recovered from anorexia nervosa to
      examine whether these abnormalities are a state or trait marker of the disease.
      To extend the understanding of functional connectivity in patients with anorexia
      nervosa, we also estimated rsFC between large-scale networks. METHODS: Girls and
      women recovered from anorexia nervosa and pair-wise, age- and sex-matched healthy
      controls underwent a resting-state fMRI scan. Using independent component
      analyses (ICA), we isolated the FPN, DMN and salience network. We used standard
      comparisons as well as a hypothesis-based approach to test the findings of our
      previous rsFC study in this recovered cohort. Temporal correlations between
      network time-course pairs were computed to investigate functional network
      connectivity (FNC). RESULTS: Thirty-one patients recovered from anorexia nervosa
      and 31 controls participated in our study. Standard group comparisons revealed
      reduced rsFC between the dorsolateral prefrontal cortex (dlPFC) and the FPN in
      the recovered group. Using a hypothesis-based approach we extended the previous
      finding of increased rsFC between the angular gyrus and the FPN in patients
      recovered from anorexia nervosa. No group differences in FNC were revealed.
      LIMITATIONS: The study design did not allow us to conclude that the difference
      found in rsFC constitutes a scar effect of the disease. CONCLUSION: This study
      suggests that some abnormal rsFC patterns found in patients recovered from
      anorexia nervosa normalize after long-term weight restoration, while distorted
      rsFC in the FPN, a network that has been associated with cognitive control, may
      constitute a trait marker of the disorder.

PMID- 27045552
TI  - Reply to Silver and Masri.

PMID- 27045554
TI  - Re: Incidence of pulmonary embolism after the first 3 months of spinal cord
      injury.

PMID- 27045553
TI  - Reliability of TMS metrics in patients with chronic incomplete spinal cord
      injury.
AB  - STUDY DESIGN: Test-retest reliability analysis in individuals with chronic
      incomplete spinal cord injury (iSCI). OBJECTIVES: The purpose of this study was
      to examine the reliability of neurophysiological metrics acquired with
      transcranial magnetic stimulation (TMS) in individuals with chronic incomplete
      tetraplegia. SETTING: Cleveland Clinic Foundation, Cleveland, Ohio, USA. METHODS:
      TMS metrics of corticospinal excitability, output, inhibition and motor map
      distribution were collected in muscles with a higher MRC grade and muscles with a
      lower MRC grade on the more affected side of the body. Metrics denoting upper
      limb function were also collected. All metrics were collected at two sessions
      separated by a minimum of two weeks. Reliability between sessions was determined
      using Spearman's correlation coefficients and concordance correlation
      coefficients (CCCs). RESULTS: We found that TMS metrics that were acquired in
      higher MRC grade muscles were approximately two times more reliable than those
      collected in lower MRC grade muscles. TMS metrics of motor map output, however,
      demonstrated poor reliability regardless of muscle choice (P=0.34; CCC=0.51).
      Correlation analysis indicated that patients with more baseline impairment and/or
      those in a more chronic phase of iSCI demonstrated greater variability of
      metrics. CONCLUSION: In iSCI, reliability of TMS metrics varies depending on the
      muscle grade of the tested muscle. Variability is also influenced by factors such
      as baseline motor function and time post SCI. Future studies that use TMS metrics
      in longitudinal study designs to understand functional recovery should be
      cautious as choice of muscle and clinical characteristics can influence
      reliability.

PMID- 27045555
TI  - Non-symmetric benzo[b]-fused BODIPYs as a versatile fluorophore platform reaching
      the NIR: a systematic study of the underlying structure-property relationship.
AB  - Ten newly synthesized non-symmetric benzo[b]-fused BODIPYs are compared with an
      extended series of nine related families (23 compounds) to gain insights into
      their structure-property relationship. The insertion of a fused indole moiety
      into the dipyrromethene core and various substituents on the proximal aryl
      including fused aromatic groups, lead to pronounced changes in the properties of
      compounds . By taking advantage of this versatile synthetic platform that allows
      facile substituent modifications and extension of the pi-conjugated system,
      significant bathochromic shifts in the absorption (lambdamax = 511-597 nm) and
      emission (601-757 nm) bands are achieved. Although the oxidation potentials of
      the compounds vary considerably throughout the series (+1.28-+1.65 V) due to the
      significant contribution of the aryl function to the HOMO, the reduction remains
      much more consistent (-0.61 to -0.79 V) as the LUMO resides primarily on the
      dipyrromethene core with little aryl contribution as calculated by DFT. For
      example, installation of a dimethylamine substituent in the para position of the
      aryl group leads to drastic modification of the optoelectronic properties of the
      absorption (597 nm) and emission (757 nm) maxima. The full electrochemical,
      photophysical and computational analyses of the compounds along with the
      structural characterization of compounds , , , and are used to rationalize the
      potential of this powerful platform.

PMID- 27045556
TI  - PSRna: Prediction of small RNA secondary structures based on reverse
      complementary folding method.
AB  - Prediction of RNA secondary structures is an important problem in computational
      biology and bioinformatics, since RNA secondary structures are fundamental for
      functional analysis of RNA molecules. However, small RNA secondary structures are
      scarce and few algorithms have been specifically designed for predicting the
      secondary structures of small RNAs. Here we propose an algorithm named "PSRna"
      for predicting small-RNA secondary structures using reverse complementary folding
      and characteristic hairpin loops of small RNAs. Unlike traditional algorithms
      that usually generate multi-branch loops and 5[Formula: see text] end self
      folding, PSRna first estimated the maximum number of base pairs of RNA secondary
      structures based on the dynamic programming algorithm and a path matrix is
      constructed at the same time. Second, the backtracking paths are extracted from
      the path matrix based on backtracking algorithm, and each backtracking path
      represents a secondary structure. To improve accuracy, the predicted RNA
      secondary structures are filtered based on their free energy, where only the
      secondary structure with the minimum free energy was identified as the candidate
      secondary structure. Our experiments on real data show that the proposed
      algorithm is superior to two popular methods, RNAfold and RNAstructure, in terms
      of sensitivity, specificity and Matthews correlation coefficient (MCC).

PMID- 27045558
TI  - The future of intravenous iron in nephrology.
AB  - Management of anaemia in chronic kidney disease (CKD) patients can be difficult
      and expensive. The recently completed Trial to Reduce Cardiovascular Events with
      Aranesp Therapy (TREAT), the largest double-blinded trial of erythropoiesis
      stimulating agents (ESA) treatment in CKD to date, provides us with a wealth of
      new information on the natural history of anaemia in Stage 3 and 4 CKD and the
      risks and benefits of use of ESAs. This section will discuss some of the TREAT
      trial results in the context of other recent studies of ESAs and intravenous iron
      in CKD patients. It will also review applying those results when choosing anaemia
      goals for an individual, and determining if iron therapy might improve anaemia.

PMID- 27045557
TI  - Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic
      encephalomyelitis (CFS/ME).
AB  - Chronic fatigue syndrome/ Myalgic encephalomyelitis (CFS/ME) is a poorly
      understood seriously debilitating disorder in which disabling fatigue is an
      universal symptom in combination with a variety of variable symptoms. The only
      drug in advanced clinical development is rintatolimod, a mismatched double
      stranded polymer of RNA (dsRNA). Rintatolimod is a restricted Toll-Like Receptor
      3 (TLR3) agonist lacking activation of other primary cellular inducers of innate
      immunity (e.g.- cytosolic helicases). Rintatolimod also activates interferon
      induced proteins that require dsRNA for activity (e.g.- 2'-5' adenylate
      synthetase, protein kinase R). Rintatolimod has achieved statistically
      significant improvements in primary endpoints in Phase II and Phase III double
      blind, randomized, placebo-controlled clinical trials with a generally well
      tolerated safety profile and supported by open-label trials in the United States
      and Europe. The chemistry, mechanism of action, clinical trial data, and current
      regulatory status of rintatolimod for CFS/ME including current evidence for
      etiology of the syndrome are reviewed. 

PMID- 27045559
TI  - Zirconium Hydride Complex Supported by a Tetradentate Carbon-Centered Tripodal
      Tris(aryloxide) Ligand: Synthesis, Structure, and Reactivity.
AB  - A dizirconium trihydride complex supported by a tetradentate carbon-centered
      tris(aryloxide) ligand [{Na(dme)}3{(O3C)Zr}2(MU-H)3] (2; [O3C] = [(3,5-(t)Bu2-2-O
      C6H2)3C](4-)) was prepared by reacting [(O3C)Zr(thf)3] (1) with NaBHEt3 in
      toluene. Exposure of 2 in THF to CO2 (1 atm) resulted in facile insertion of CO2
      into Zr-H bonds, yielding a formate complex [{Na(thf)2}3{(O3C)Zr}2(MU-O2CH)3]
      (3). Treatment of 2 with P4 in toluene led to formation of
      [Na(thf)5][{Na(thf)2}2{(O3C)Zr}2(MU-P3)] (4) and PH3, in which hydrogenation of
      P4 took place. Complex 2 reacted with Me3SiN3 to afford an azide-bridged
      cyclotrimer [{Na(thf)2}{(O3C)ZrN3(thf)}]3 (5) with concomitant liberation of
      Me3SiH. The molecular structures of these complexes 2-5 have been determined by X
      ray diffraction analyses. 

PMID- 27045560
TI  - Promoting patient-centred fundamental care in acute healthcare systems.
AB  - Meeting patients' fundamental care needs is essential for optimal safety and
      recovery and positive experiences within any healthcare setting. There is growing
      international evidence, however, that these fundamentals are often poorly
      executed in acute care settings, resulting in patient safety threats, poorer and
      costly care outcomes, and dehumanising experiences for patients and families.
      Whilst care standards and policy initiatives are attempting to address these
      issues, their impact has been limited. This discussion paper explores, through a
      series of propositions, why fundamental care can be overlooked in sophisticated,
      high technology acute care settings. We argue that the central problem lies in
      the invisibility and subsequent devaluing of fundamental care. Such care is
      perceived to involve simple tasks that require little skill to execute and have
      minimal impact on patient outcomes. The propositions explore the potential
      origins of this prevailing perception, focusing upon the impact of the biomedical
      model, the consequences of managerial approaches that drive healthcare cultures,
      and the devaluing of fundamental care by nurses themselves. These multiple
      sources of invisibility and devaluing surrounding fundamental care have rendered
      the concept underdeveloped and misunderstood both conceptually and theoretically.
      Likewise, there remains minimal role clarification around who should be
      responsible for and deliver such care, and a dearth of empirical evidence and
      evidence-based metrics. In explicating these propositions, we argue that key to
      transforming the delivery of acute healthcare is a substantial shift in the
      conceptualisation of fundamental care. The propositions present a cogent argument
      that counters the prevailing perception that fundamental care is basic and does
      not require systematic investigation. We conclude by calling for the explicit
      valuing and embedding of fundamental care in healthcare education, research,
      practice and policy. Without this re-conceptualisation and subsequent action,
      poor quality, depersonalised fundamental care will prevail. 

PMID- 27045561
TI  - Characteristics of shift work and their impact on employee performance and
      wellbeing: A literature review.
AB  - OBJECTIVES: To identify the characteristics of shift work that have an effect on
      employee's performance (including job performance, productivity, safety, quality
      of care delivered, errors, adverse events and client satisfaction) and wellbeing
      (including burnout, job satisfaction, absenteeism, intention to leave the job) in
      all sectors including healthcare. DESIGN: A scoping review of the literature was
      undertaken. DATA SOURCES: We searched electronic databases (CINAHL, MEDLINE,
      PsychINFO, SCOPUS) to identify primary quantitative studies. REVIEW METHODS: The
      search was conducted between January and March 2015. Studies were drawn from all
      occupational sectors (i.e. health and non health), meeting the inclusion
      criteria: involved participants aged >=18 who have been working shifts or serve
      as control group for others working shifts, exploring the association of
      characteristics of shift work with at least one of the selected outcomes.
      Reference lists from retrieved studies were checked to identify any further
      studies. RESULTS: 35 studies were included in the review; 25 studies were
      performed in the health sector. A variety of shift work characteristics are
      associated with compromised employee's performance and wellbeing. Findings from
      large multicentre studies highlight that shifts of 12h or longer are associated
      with jeopardised outcomes. Working more than 40h per week is associated with
      adverse events, while no conclusive evidence was found regarding working a
      'Compressed Working Week'; working overtime was associated with decreased job
      performance. Working rotating shifts was associated with worse job performance
      outcomes, whilst fixed night shifts appeared to enable resynchronisation.
      However, job satisfaction of employees working fixed nights was reduced. Timely
      breaks had a positive impact on employee fatigue and alertness, whilst quick
      returns between shifts appeared to increase pathologic fatigue. The effect of
      shift work characteristics on outcomes in the studies reviewed is consistent
      across occupational sectors. CONCLUSIONS: This review highlighted the complexity
      that encompasses shift work, but many studies do not account for this complexity.
      While some consistent associations emerge (e.g. 12h shifts and jeopardised
      outcomes), it is not always possible to conclude that results are not confounded
      by unmeasured factors.

PMID- 27045562
TI  - Prevalence and predictors of compassion fatigue, burnout and compassion
      satisfaction among oncology nurses: A cross-sectional survey.
AB  - BACKGROUND: Cancer is a leading cause of death worldwide. Given the complexity of
      caring work, recent studies have focused on the professional quality of life of
      oncology nurses. China, the world's largest developing country, faces heavy
      burdens of care for cancer patients. Chinese oncology nurses may be encountering
      the negative side of their professional life. However, studies in this field are
      scarce, and little is known about the prevalence and predictors of oncology
      nurses' professional quality of life. OBJECTIVES: To describe and explore the
      prevalence of predictors of professional quality of life (compassion fatigue,
      burnout and compassion satisfaction) among Chinese oncology nurses under the
      guidance of two theoretical models. DESIGN: A cross-sectional design with a
      survey. SETTINGS: Ten tertiary hospitals and five secondary hospitals in
      Shanghai, China. PARTICIPANTS: A convenience and cluster sample of 669 oncology
      nurses was used. All of the nurses worked in oncology departments and had over 1
      year of oncology nursing experience. Of the selected nurses, 650 returned valid
      questionnaires that were used for statistical analyses. METHODS: The participants
      completed the demographic and work-related questionnaire, the Chinese version of
      the Professional Quality of Life Scale for Nurses, the Chinese version of the
      Jefferson Scales of Empathy, the Simplified Coping Style Questionnaire, the
      Perceived Social Support Scale, and the Chinese Big Five Personality Inventory
      brief version. Descriptive statistics, t-tests, one-way analysis of variance,
      simple and multiple linear regressions were used to determine the predictors of
      the main research variables. RESULTS: Higher compassion fatigue and burnout were
      found among oncology nurses who had more years of nursing experience, worked in
      secondary hospitals and adopted passive coping styles. Cognitive empathy,
      training and support from organizations were identified as significant
      protectors, and 'perspective taking' was the strongest predictor of compassion
      satisfaction, explaining 23.0% of the variance. Personality traits of openness
      and conscientiousness were positively associated with compassion satisfaction,
      while neuroticism was a negative predictor, accounting for 24.2% and 19.8% of the
      variance in compassion fatigue and burnout, respectively. CONCLUSIONS: Oncology
      care has unique features, and oncology nurses may suffer from more work-related
      stressors compared with other types of nurses. Various predictors can influence
      the professional quality of life, and some of these should be considered in the
      Chinese nursing context. The results may provide clues to help nurse
      administrators identify oncology nurses' vulnerability to compassion fatigue and
      burnout and develop comprehensive strategies to improve their professional
      quality of life.

PMID- 27045563
TI  - Practices and impacts post-exposure to blood and body fluid in operating room
      nurses: A cross-sectional study.
AB  - BACKGROUND: Improper or inadequate actions taken after blood and body fluid
      exposures place individuals at risk for infection with bloodborne pathogens. This
      has potential, significant impact for health and well-being. OBJECTIVES: To
      evaluate the practices and the personal impact experienced following blood and
      body fluid exposures among operating room nurses. DESIGN: A cross-sectional,
      multi-center study. SETTINGS: Government and private hospitals from all parts of
      Thailand. PARTICIPANTS: Operating room nurses from 247 hospitals. METHODS: A
      questionnaire eliciting responses on characteristics, post-exposure practices,
      and impacts was sent to 2500 operating room nurses. RESULTS: Usable
      questionnaires were returned by 2031 operating room nurses (81.2%). Of these 1270
      had experience with blood and body fluid exposures (62.5%). Most operating room
      nurses did not report blood and body fluid exposures (60.9%). The major reasons
      of underreporting were low risk source (40.2%) and belief that they were not
      important to report (16.3%). Improper post-exposure practices were identified,
      9.8% did not clean exposure area immediately, 18.0% squeezed out the wound, and
      71.1% used antiseptic solution for cleansing a puncture wound. Post-exposure,
      58.5% of them sought counseling, 16.3% took antiretroviral prophylaxis, 23.8% had
      serologic testing for hepatitis B and 43.1% for hepatitis C. The main personal
      impacts were anxiety (57.7%), stress (24.2%), and insomnia (10.2%). CONCLUSIONS:
      High underreporting, inappropriate post-exposure practices and impacts of
      exposure were identified from this study. Comprehensive education and effective
      training of post-exposure management may be keys to resolving these important
      problems.

PMID- 27045564
TI  - The burden of venipuncture pain in neonatal intensive care units: EPIPPAIN 2, a
      prospective observational study.
AB  - BACKGROUND: Newborns in intensive care units (ICUs) undergo numerous painful
      procedures including venipunctures. Skin-breaking procedures have been associated
      with adverse neurodevelopment long-term effects in very preterm neonates. The
      venipuncture frequency and its real bedside pain management treatment are not
      well known in this setting. OBJECTIVES: To describe venipuncture frequency, its
      pain intensity, and the analgesic approach in ICU newborns; to determine the
      factors associated with the lack of preprocedural analgesia and with a high pain
      score during venipuncture. DESIGN: Further analysis of EPIPPAIN 2 (Epidemiology
      of Procedural Pain In Neonates), which is a descriptive prospective epidemiologic
      study. SETTING: All 16 neonatal and pediatric ICUs in the Paris region in France.
      PARTICIPANTS: All newborns in the ICU with a maximum corrected age under 45 weeks
      of gestation on admission who had at least one venipuncture during the study
      period. METHODS: Data on all venipunctures, their pain score assessed with the
      DAN scale and their corresponding analgesic therapies were prospectively
      collected. The inclusion period lasted six weeks, from June 2, 2011, to July 12,
      2011. Newborns were followed from their admission to the 14th day of their ICU
      stay or discharge, whichever occurred first. RESULTS: 495 newborns who underwent
      venipunctures were included. The mean (SD) gestational age was 33.0 (4.4) weeks
      and duration of participation was 8.0 (4.5) days. A total of 257 (51.9%) neonates
      were very preterm (<33 weeks). The mean (SD; range) number of venipunctures per
      neonate during the study period was 3.8 (2.8; 1-19) for all neonates and 4.1
      (2.9; 1-17) for neonates <33 weeks. Of the 1887 venipunctures, 1164 (61.7%) were
      performed successfully in one attempt, 437 (23.2%) with continuous analgesia,
      1434 (76.0%) with specific preprocedural analgesia. In multivariate models, lack
      of preprocedural analgesia was associated with higher disease-severity score,
      intrauterine growth retardation, invasive or noninvasive ventilation,
      venipuncture performed on the first day of hospitalization or at nighttime, and
      the use of continuous sedation/analgesia. High pain scores were significantly
      associated with absence of parents during procedures, surgery during the study
      period, and higher number of attempts. CONCLUSIONS: Venipuncture is very frequent
      in preterm and term neonates in the ICUs. 76% were performed with preprocedural
      analgesia. Strategies to reduce the number of attempts and to promote parental
      presence seem necessary.

PMID- 27045566
TI  - The effectiveness of Internet-based e-learning on clinician behaviour and patient
      outcomes: A systematic review.
AB  - BACKGROUND: The contemporary health workforce has a professional responsibility
      to maintain competency in practice. However, some difficulties exist with access
      to ongoing professional development opportunities, particularly for staff in
      rural and remote areas and those not enrolled in a formal programme of study. E
      learning is at the nexus of overcoming these challenges. The benefits of e
      learning have been reported in terms of increased accessibility to education,
      improved self-efficacy, knowledge generation, cost effectiveness, learner
      flexibility and interactivity. What is less clear, is whether improved self
      efficacy or knowledge gained through e-learning influences healthcare
      professional behaviour or skill development, whether these changes are sustained,
      and whether these changes improve patient outcomes. OBJECTIVE: To identify,
      appraise and synthesise the best available evidence for the effectiveness of e
      learning programmes on health care professional behaviour and patient outcomes.
      DESIGN: A systematic review of randomised controlled trials was conducted to
      assess the effectiveness of e-learning programmes on clinician behaviour and
      patient outcomes. Electronic databases including CINAHL, Embase, ERIC, MEDLINE,
      Mosby's Index, Scopus and Cochrane - CENTRAL were searched in July 2014 and again
      in July 2015. QUALITY ASSESSMENT AND DATA EXTRACTION: Studies were reviewed and
      data extracted by two independent reviewers using the Joanna Briggs Institute
      standardised critical appraisal and data extraction instruments. DATA SYNTHESIS:
      Seven trials met the inclusion criteria for the analysis. Due to substantial
      instructional design, subject matter, study population, and methodological
      variation between the identified studies, statistical pooling was not possible
      and a meta-analysis could not be performed. Consequently, the findings of this
      systematic review are presented as a narrative review. RESULTS: The results
      suggest that e-learning was at least as effective as traditional learning
      approaches, and superior to no instruction at all in improving health care
      professional behaviour. There was variation in behavioural outcomes depending on
      the skill being taught, and the learning approach utilised. No papers were
      identified that reported the effectiveness of an e-learning programme on patient
      outcomes. CONCLUSION: This review found insufficient evidence regarding the
      effectiveness of e-learning on healthcare professional behaviour or patient
      outcomes, consequently further research in this area is warranted. Future
      randomised controlled trials should adhere to the CONSORT reporting guidelines in
      order to improve the quality of reporting, to allow evaluation of the
      effectiveness of e-learning programmes on healthcare professional behaviour and
      patient outcomes.

PMID- 27045565
TI  - Occupational factors associated with obesity and leisure-time physical activity
      among nurses: A cross sectional study.
AB  - BACKGROUND AND OBJECTIVE: Adverse working conditions contribute to obesity and
      physical inactivity. The purpose of this study was to examine the associations of
      occupational factors with obesity and leisure-time physical activity among
      nurses. METHODS: This study used cross-sectional data of 394 nurses (mean age 48
      years, 91% females, 61% white) randomly selected from the California Board of
      Registered Nursing list. Data on demographic and employment characteristics,
      musculoskeletal symptom comorbidity, physical and psychosocial occupational
      factors, body mass index (BMI), and physical activity were collected using postal
      and on-line surveys from January to July in 2013. RESULTS: Of the participants,
      31% were overweight and 18% were obese; 41% engaged in regular aerobic physical
      activity (>= 150 min/week) and 57% performed regular muscle-strengthening
      activity (>= 2 days/week). In multivariable logistic regression models,
      overweight/obesity (BMI >= 25 kg/m(2)) was significantly more common among nurse
      managers/supervisors (OR=2.54, 95% CI: 1.16-5.59) and nurses who worked full-time
      (OR=2.18, 95% CI: 1.29-3.70) or worked >= 40 h per week (OR=2.53, 95% CI: 1.58
      4.05). Regular aerobic physical activity was significantly associated with high
      job demand (OR=1.63, 95% CI: 1.06-2.51). Nurses with passive jobs (low job demand
      combined with low job control) were significantly less likely to perform aerobic
      physical activity (OR=0.49, 95% CI: 0.26-0.93). Regular muscle-strengthening
      physical activity was significantly less common among nurses working on non-day
      shifts (OR=0.55, 95% CI: 0.34-0.89). Physical workload was not associated with
      obesity and physical activity. CONCLUSIONS: Our study findings suggest that
      occupational factors significantly contribute to obesity and physical inactivity
      among nurses. Occupational characteristics in the work environment should be
      considered in designing effective workplace health promotion programs targeting
      physical activity and obesity among nurses.

PMID- 27045568
TI  - Why was my paper rejected? Editors' reflections on common issues which influence
      decisions to reject papers submitted for publication in academic nursing
      journals.

PMID- 27045567
TI  - Starting Out: A time-lagged study of new graduate nurses' transition to practice.
AB  - BACKGROUND: As the nursing profession ages, new graduate nurses are an invaluable
      health human resource. OBJECTIVES: The purpose of this study was to investigate
      factors influencing new graduate nurses' successful transition to their full
      professional role in Canadian hospital settings and to determine predictors of
      job and career satisfaction and turnover intentions over a one-year time period
      in their early employment. DESIGN: A national two-wave survey of new graduate
      nurses across Canada. PARTICIPANTS: A random sample of 3906 Registered Nurses
      with less than 3 years of experience currently working in direct patient care was
      obtained from the provincial registry databases across Canada. At Time 1, 1020 of
      3743 eligible nurses returned completed questionnaires (usable response
      rate=27.3%). One year later, Time 1 respondents were mailed a follow-up survey;
      406 returned a completed questionnaire (response rate=39.8%). METHODS: Surveys
      containing standardized questionnaires were mailed to participants' home address.
      Descriptive statistics, correlations, and hierarchical linear regression analyses
      were conducted using SPSS software. RESULTS: Overall, new graduate nurses were
      positive about their experiences and committed to nursing. However, over half of
      new nurses in the first year of practice reported high levels of emotional
      exhaustion and many witnessed or experienced incivility (24-42%) at work.
      Findings from hierarchical linear regression analyses revealed that situational
      and personal factors explained significant amounts of variance in new graduate
      nurses' job and career satisfaction and turnover intentions. Cynicism was a
      significant predictor of all four outcomes one year later, while Psycap predicted
      job and career satisfaction and career turnover intentions. CONCLUSIONS: Results
      provide a look into the worklife experiences of Canadian new graduate nurses over
      a one-year time period and identify factors that influence their job-related
      outcomes. These findings show that working conditions for new graduate nurses are
      generally positive and stable over time, although workplace mistreatment is an
      issue to be addressed.

PMID- 27045569
TI  - Understanding Health and Health-Related Behavior of Users of Internet Health
      Information.
AB  - BACKGROUND: Little is known about how actual use of Internet health-related
      information is associated with health or health-related behavior. METHODS: Using
      a nationally representative sample of 34,525 from 2012, this study examined the
      demographics of users of Internet health-related information (users), reports
      estimates of association with several health and behavioral outcomes adjusting
      for demographic factors, and analyzed the sample by education level, race,
      gender, and age. RESULTS: Analysis of a large nationally representative sample
      shows evidence that users of health-related information (users) on the Internet
      are younger, more educated, more likely to be insured, more likely to be female,
      and less likely to be African American. After adjusting for demographic
      differences, users are more likely to have been diagnosed with hypertension,
      cancer, stroke, and high cholesterol, but no evidence of current hypertension,
      weight-related issues, or being in fair or poor health. Users are less likely to
      smoke and among smokers are more likely to attempt quitting. Users are more
      likely to exercise, get a flu shot, pap smear, mammogram, HIV test, colon cancer
      screening, blood pressure check, and cholesterol check, but likely to be heavy
      drinkers. With few exceptions, results appear robust across gender, age groups,
      level of education, and ethnicity. CONCLUSIONS: Use is generally positively
      associated with prior diagnosis for several conditions and behaviors related to
      improved health, but I find no relationship with existing health status. The
      association between use of health-related Internet information and health-related
      behavior seems robust across levels of education, age, gender, and race.

PMID- 27045570
TI  - Chan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the
      Aryl Amine Problem.
AB  - The Chan-Evans-Lam reaction is a valuable C-N bond forming process. However, aryl
      boronic acid pinacol (BPin) ester reagents can be difficult coupling partners
      that often deliver low yields, in particular in reactions with aryl amines.
      Herein, we report effective reaction conditions for the Chan-Evans-Lam amination
      of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was
      found to enable effective C-N bond formation using aryl amines while EtOH is not
      required for the coupling of alkyl amines.

PMID- 27045571
TI  - Adaptively Compressed Exchange Operator.
AB  - The Fock exchange operator plays a central role in modern quantum chemistry. The
      large computational cost associated with the Fock exchange operator hinders
      Hartree-Fock calculations and Kohn-Sham density functional theory calculations
      with hybrid exchange-correlation functionals, even for systems consisting of
      hundreds of atoms. We develop the adaptively compressed exchange operator (ACE)
      formulation, which greatly reduces the computational cost associated with the
      Fock exchange operator without loss of accuracy. The ACE formulation is not
      dependent on the size of the band gap, and thus can be applied to insulating and
      semiconducting systems, as well as metallic systems. In an iterative framework
      for solving Hartree-Fock-like systems, such as that observed in planewave-based
      methods, the ACE formulation only requires moderate modification of the code. The
      ACE formulation can also be advantageous for other types of basis sets,
      especially when the storage cost of the exchange operator is expensive. Numerical
      results indicate that the ACE formulation can become advantageous, even for small
      systems with tens of atoms. In particular, the cost of each self-consistent field
      iteration for the electron density in the ACE formulation is only marginally
      larger than that of the generalized gradient approximation (GGA) calculation, and
      thus offers orders-of-magnitude acceleration for Hartree-Fock-like calculations. 

PMID- 27045573
TI  - Effect of Aluminum Substrate Surface Modification on Wettability and Freezing
      Delay of Water Droplet at Subzero Temperatures.
AB  - In this study, we have investigated the freezing delay of a water droplet on
      precooled substrates of an aluminum alloy that is commonly used for heat
      exchanger fins. The surfaces of the substrates were modified to obtain surfaces
      with different hydrophilicity/hydrophobicity and different surface chemistry but
      without significantly modifying the surface topography. The freezing delays and
      water contact angles were measured as a function of the substrate temperature and
      the results were compared to the predictions of the heterogeneous ice nucleation
      theory. Although the trends for each sample followed the trend in this theory,
      the differences in the extents of freezing delays were in apparent disagreement
      with the predictions. Concretely, a slightly hydrophilic substrate modified by (3
      aminopropyl) triethoxysilane (APTES) showed longer freezing delays than both more
      hydrophilic and more hydrophobic substrates. We suggest that this is because this
      particular surface chemistry prevents ice formation at the interface of the
      substrate, prior to the deposition of the water droplet. On the basis of our
      results, we suggest that not only wettability and topography but also the
      concrete surface chemistry plays a significant role in the kinetics of the ice
      formation process when a water droplet is placed on a precooled substrate.

PMID- 27045572
TI  - HbA1c and Risks of All-Cause and Cause-Specific Death in Subjects without Known
      Diabetes: A Dose-Response Meta-Analysis of Prospective Cohort Studies.
AB  - Whether HbA1c levels are associated with mortality in subjects without known
      diabetes remains controversial. Moreover, the shape of the dose-response
      relationship on this topic is unclear. Therefore, a dose-response meta-analysis
      was conducted. PubMed and EMBASE were searched. Summary hazard ratios (HRs) were
      calculated using a random-effects model. Twelve studies were included. The
      summary HR per 1% increase in HbA1c level was 1.03 [95% confidence interval (CI)
      = 1.01-1.04] for all-cause mortality, 1.05 [95% CI = 1.02-1.07) for
      cardiovascular disease (CVD) mortality, and 1.02 (95% CI = 0.99-1.07) for cancer
      mortality. After excluding subjects with undiagnosed diabetes, the aforementioned
      associations remained significant for CVD mortality only. After further excluding
      subjects with prediabetes, all aforementioned associations presented non
      significance. Evidence of a non-linear association between HbA1c and mortality
      from all causes, CVD and cancer was found (all Pnon-linearity < 0.05). The dose
      response curves were relatively flat for HbA1c less than around 5.7%, and rose
      steeply thereafter. In conclusion, higher HbA1c level is associated with
      increased mortality from all causes and CVD among subjects without known
      diabetes. However, this association is driven by those with undiagnosed diabetes
      or prediabetes. The results regarding cancer mortality should be treated with
      caution due to limited studies. 

PMID- 27045574
TI  - Compound heterozygous GJB2 mutations associated to a consanguineous Han family
      with autosomal recessive non-syndromic hearing loss.
AB  - CONCLUSION: This study demonstrates that the gap junction protein beta-2 gene
      (GJB2) p.R32C and p.L79Cfs*3 variants are associated to a consanguineous family
      with autosomal recessive non-syndromic hearing loss (ARNSHL). The p.R32C variant
      is found for the first time in the NSHL patients of Han Chinese origin. The
      finding sheds new light on the accurate genetic diagnosis and counseling for the
      family. OBJECTIVE: ARNSHL is a highly heterogeneous genetic disease. ARNSHL
      usually displays non-progressive congenital or pre-lingual deafness. In this
      study, the aim is to detect the disease-causing mutation(s) in a Han family with
      ARNSHL. METHODS: A consanguineous Han family with ARNSHL was enrolled. Two
      hundred ethnicity-matched unrelated subjects without any hearing impairments were
      used as normal controls. Exome sequencing and Sanger sequencing were applied to
      identify the causative mutation in the ARNSHL family. RESULTS: Compound
      heterozygous variants c.94C > T (p.R32C) and c.235delC (p.L79Cfs*3) in the GJB2
      gene were identified in the two patients of the ARNSHL family, and the
      heterozygous GJB2 c.94C > T and c.235delC variants were identified in his
      unaffected father and mother, respectively. The two variants in the GJB2 gene
      were absent in the 200 unrelated controls.

PMID- 27045575
TI  - Epigenetic regulation of NKG2D ligands is involved in exacerbated atherosclerosis
      development in Sirt6 heterozygous mice.
AB  - Sirt6 is a member of the class III histone deacetylase family which is associated
      with aging and longevity. Sirt6 deficient mice show an aging-like phenotype,
      while male transgenic mice of Sirt6 show increased longevity. Sirt6 acts as a
      tumor suppressor and deficiency of Sirt6 leads to cardiac hypertrophy and heart
      failure. Whether Sirt6 is involved in atherosclerosis development, the major
      cause of cardiovascular diseases, is unknown. We found that the expression of
      Sirt6 is lower in human atherosclerotic plaques than that in controls. When
      Sirt6(+/-)ApoE(-/-) and ApoE(-/-) mice are fed with high fat diet for 16 weeks,
      Sirt6(+/-)ApoE(-/-) mice show increased plaque fromation and exhibit feature of
      plaque instability. Furthermore, Sirt6 downregulation increases expression of
      NKG2D ligands, which leads to increased cytokine expression. Blocking NKG2D
      ligand almost completely blocks this effect. Mechanistically, Sirt6 binds to
      promoters of NKG2D ligand genes and regulates the H3K9 and H3K56 acetylation
      levels. 

PMID- 27045576
TI  - Clinical value of intratumoral metabolic heterogeneity in [18F]FDG PET/CT for
      prediction of recurrence in patients with locally advanced colorectal cancer.
AB  - BACKGROUND: The aim of this study was to find a reliable predictor of recurrence
      in patients with locally advanced colorectal cancer. METHODS: We enrolled 96
      patients for this retrospective study. We investigated metabolic (SUVmax,
      metabolic tumor volume, total lesion glycolysis, and heterogeneity), clinical
      (age, sex, stage, and CEA level) and pathologic (Ki-67, p53, CD31, COX-2, E
      cadherin and EGFR) parameters. The coefficient of variation (COV) was chosen to
      assess heterogeneity of [18F]FDG uptake by dividing the standard deviation of the
      SUV by SUVmean. Recurrence-free survival was compared with each metabolic,
      clinical and pathologic parameters by using univariate and multivariate survival
      analysis. RESULTS: Among 96 patients, 19 patients (19.8%) showed disease
      recurrence. In the ROC analysis, the optimal cutoff values of SUVmax, metabolic
      tumor volume (cm3), total lesion glycolysis (cm3), and metabolic heterogeneity
      were determined as 17.6, 10.05, 232.46, and 0.48, respectively. In univariate
      analysis, probability of recurrence was statistically increased in those with
      metabolic tumor volume >10.05 (P=0.045), and those with metabolic heterogeneity
      >0.48 (P=0.031). In multivariate analysis, metabolic heterogeneity was the only
      independent prognostic factor (HR 4.56, 95% CI 1.57-13.23, P=0.006). CONCLUSIONS:
      Intratumoral metabolic heterogeneity assessed by COV is a reliable predictive
      factor for disease recurrence in patients with locally advanced colorectal
      cancer. Therefore, its application could be an important step for personalized
      management of colorectal cancer.

PMID- 27045577
TI  - Sympathetic denervation in patients with ischemic cardiomyopathy and risk on
      ventricular tachy-arrhythmias. A pilot study.
AB  - BACKGROUND: Patients with ischemic cardiomyopathy (ICM) are at risk for
      ventricular arrhythmias and are protected by an implantable cardioverter
      defibrillator (ICD). Visualization of cardiac sympathetic innervation may play an
      additional role to left ventricular ejection fraction (LVEF) in identifying those
      patients who will benefit from ICD therapy. The purpose of this study was to
      detect the role of sympathetic denervation in the genesis of ventricular
      arrhythmias in ICM patients. METHODS: Twenty patients with ICM and LVEF <30% were
      included in this pilot study. Included patients were equally stratified into two
      groups: no history of arrhythmias (group A) and recurrent arrhythmias (group B).
      All patients underwent cardiac sympathetic denervation (using carbon-11 labelled
      meta-hydroxy-ephedrine ([11C]-mHED)), myocardial ischemia and viability
      detection. Patients were followed up to one year after the imaging studies.
      RESULTS: Mean age was 63+/-7.5 years. Mean global retention of [11C]-mHED was
      0.055+/-0,012 min-1, and was not different between the two patient groups:
      0.056+/-0.011 min-1 vs. 0.054+/-0.013 min-1 for group A vs. group B,
      respectively. During follow-up, seven patients developed ventricular arrhythmias,
      and four patients died. No difference in [11C]-mHED retention was found between
      patients with and without ventricular arrhythmia during follow-up. However, size
      of denervated area was larger in patients who died during follow-up: 10+/-1
      segments vs. 6+/-2 segments, P=0.002. CONCLUSIONS: Cardiac sympathetic
      innervation is impaired in patients with ischemic cardiomyopathy. All-cause
      mortality occurred in those patients with large areas of [11C]-mHED defect.

PMID- 27045578
TI  - Development and validation of a diabetes self-management instrument for older
      African-Americans.
AB  - The objective of this study was to develop and validate a new diabetes self
      management instrument for older African-Americans 65 years of age and older. The
      Self-Care Utility Geriatric African-American Rating (SUGAAR) was developed using
      the American Diabetes Association's standards for the management of type 2
      diabetes in older adults and cognitive interviews with older African-Americans.
      The instrument underwent extensive review by a panel of experts, two rounds of
      cognitive interviews, and a pilot test before it was administered in an interview
      format to 125 community-dwelling older African-Americans. The instrument
      demonstrated content validity and significant, but modest, convergent validity
      with items from an established diabetes self-management instrument. Social
      workers and health care professionals can use the SUGARR to assess diabetes self
      management and to identify areas for education and support for older African
      Americans with type 2 diabetes.

PMID- 27045579
TI  - [Role of fundus examination in Aicardi syndrome].

PMID- 27045580
TI  - Intranasal triamcinolone use during pregnancy and the risk of adverse pregnancy
      outcomes.
AB  - BACKGROUND: Intranasal corticosteroid use during pregnancy has increased over the
      past decade. OBJECTIVE: We aim to estimate the safety of intranasal triamcinolone
      use during pregnancy, which was introduced for over-the-counter use in October
      2013. METHODS: We designed a population-based prospective cohort study. From a
      cohort of 289,723 pregnancies in Montreal, Quebec, Canada, from 1998-2008,
      intranasal triamcinolone-exposed, other intranasal corticosteroid-exposed, and
      nonexposed women during the first trimester were studied for major congenital
      malformations (overall and organ specific) and spontaneous abortions and during
      the second/third trimesters for small-for-gestational age (SGA) newborns. The
      first trimester is the time window of interest for malformations and spontaneous
      abortion (organogenesis), and the second/third trimesters are the time windows of
      interest for SGA (fetal growth). Logistic regression model-based generalized
      estimating equations were used. RESULTS: Adjusting for potential confounders, use
      of intranasal triamcinolone during the first trimester of pregnancy was not
      significantly associated with the risk of overall congenital malformations (odds
      ratio [OR], 0.88; 95% CI, 0.60-1.28; 31 exposed cases) compared with nonexposure;
      however, it was associated with the risk of respiratory defects (OR, 2.71; 95%
      CI, 1.11-6.64; 5 exposed cases). Pregnancy exposure to intranasal triamcinolone
      was not significantly associated with the risk of spontaneous abortion (OR, 1.04;
      95% CI, 0.76-1.43; 50 exposed cases). No association was found between second- or
      third-trimester exposure to intranasal triamcinolone and the risk of SGA (OR,
      1.06; 95% CI, 0.79-1.43; 50 exposed cases). CONCLUSIONS: Maternal exposure to
      intranasal triamcinolone during pregnancy was not associated with the risk of
      SGA/spontaneous abortions/overall malformations. However, it has been shown to
      increase the risk of respiratory system defects. Chance finding cannot be ruled
      out.

PMID- 27045581
TI  - Cytometry by time-of-flight immunophenotyping identifies a blood Sjogren's
      signature correlating with disease activity and glandular inflammation.
AB  - BACKGROUND: Mass cytometry has recently emerged as a promising tool for clinical
      research. However, few studies have demonstrated its benefit for patient
      stratification and biomarker identification. Primary Sjogren's syndrome (pSS) is
      a prototype of chronic autoimmune disease, the pathogenesis of which remains
      unclear and for which treatment does not exist. OBJECTIVE: This observational
      case-control study was designed to discover new cellular biomarkers and
      therapeutic targets in patients with pSS. METHODS: Forty-nine patients with pSS
      and 45 control subjects were enrolled for clinical evaluation and mass cytometry
      quantification of 34 protein markers in blood. For a third of these subjects,
      matched labial salivary gland biopsy specimens were also analyzed by mass
      cytometry and immunohistochemistry. RESULTS: In salivary gland biopsy specimens
      from patients with pSS, we identified a high number of activated CD8(+) T cells,
      terminally differentiated plasma cells, and activated epithelial cells, pointing
      to new pathogenic mechanisms for future clinical intervention. In blood, we
      identified a 6-cell disease signature defined by decreased numbers of CD4 and
      memory B lymphocytes, decreased plasmacytoid dendritic cell numbers, and
      increased representation of activated CD4 and CD8 T cells and plasmablasts. These
      blood cellular components correlated with clinical parameters and, when taken
      together, clustered patients into subsets with distinct disease activity and
      glandular inflammation. CONCLUSION: This first application of mass cytometry to a
      well-stratified clinical cohort and small biopsy tissues establishes the benefits
      of such an approach for the discovery of new biomarkers and therapeutic targets.
      Similar high-dimensional immunophenotyping strategies could be implemented in
      longitudinal and interventional clinical settings in this and other disease
      areas.

PMID- 27045582
TI  - Cesarean section changes neonatal gut colonization.
AB  - BACKGROUND: Delivery by means of cesarean section has been associated with
      increased risk of childhood immune-mediated diseases, suggesting a role of early
      bacterial colonization patterns for immune maturation. OBJECTIVE: We sought to
      describe the influence of delivery method on gut and airway colonization patterns
      in the first year of life in the Copenhagen Prospective Studies on Asthma in
      Childhood2010 (COPSAC2010) birth cohort. METHODS: Seven hundred children from the
      COPSAC2010 birth cohort participated in this analysis. Fecal samples were
      collected at age 1 week, 1 month, and 1 year, and hypopharyngeal aspirates were
      collected at age 1 week, 1 month, and 3 months and cultured for bacteria.
      Detailed information on delivery method, intrapartum antibiotics, and lifestyle
      factors was obtained by personal interviews. RESULTS: Seventy-eight percent of
      the children were born by means of natural delivery, 12% by means of emergency
      cesarean section, and 9% by means of elective cesarean section. Birth by means of
      cesarean section was significantly associated with colonization of the intestinal
      tract by Citrobacter freundii, Clostridium species, Enterobacter cloacae,
      Enterococcus faecalis, Klebsiella oxytoca, Klebsiella pneumoniae, and
      Staphylococcus aureus at age 1 week, whereas colonization by Escherichia coli was
      associated with natural birth. At age 1 month, these differences were less
      prominent, and at age 1 year, they were not apparent, which was confirmed by
      means of multivariate data-driven partial least squares analyses. The initial
      airway microbiota was unaffected by birth method. CONCLUSION: Delivery by means
      of cesarean section was associated with early colonization patterns of the
      neonatal gut but not of the airways. The differences normalized within the first
      year of life. We speculate that microbial derangements, as indicated in our
      study, can demonstrate a possible link between delivery by means of cesarean
      section and immune-mediated disease.

PMID- 27045583
TI  - Selecting the correct treatment for asthma adherence studies.

PMID- 27045584
TI  - Reply.

PMID- 27045585
TI  - Neuropsychological Assessment of Hippocampal Integrity.
AB  - Finding methods to describe subcortical processes assisting cognition is an
      important concern for clinical neuropsychological practice. In this study, we
      reviewed the literature concerning the relationship between a neuropsychological
      instrument and the underlying neural substructure. We examined evidence
      indicating that one of the oldest neuropsychological tests still in use, the Rey
      Auditory Verbal Learning Test (RAVLT), includes reliable indicators of
      hippocampal integrity. We reviewed studies investigating the neural structures
      underlying seven tasks generated by the RAVLT, from the perspective of whether
      the performance of these tasks is dependent on the hippocampus. We found support
      for our hypothesis in five cases: learning capacity, proactive interference,
      immediate recall, delayed recall, and delayed recognition. No support for our
      hypothesis was found with regard to short-term memory and retroactive
      interference. The RAVLT appears to be a reliable tool for assessing the integrity
      of the hippocampus and for the early detection of dysfunction. There is a need
      for such assessments, due to the crucial role of the hippocampus in cognition,
      for instance, in terms of predicting future outcomes.

PMID- 27045586
TI  - MicroRNA-3646 Contributes to Docetaxel Resistance in Human Breast Cancer Cells by
      GSK-3beta/beta-Catenin Signaling Pathway.
AB  - Acquisition of resistance to docetaxel (Doc) is one of the most important
      problems in treatment of breast cancer patients, but the underlying mechanisms
      are still not fully understood. In present study, Doc-resistant MDA-MB-231 and
      MCF-7 breast cancer cell lines (MDA-MB-231/Doc and MCF-7/Doc) were successfully
      established in vitro by gradually increasing Doc concentration on the basis of
      parental MDA-MB-231 and MCF-7 cell lines (MDA-MB-231/S and MCF-7/S). The
      potential miRNAs relevant to the Doc resistance were screened by miRNA
      microarray. We selected 5 upregulated miRNAs (has-miR-3646, has-miR-3658, has-miR
      4438, has-miR-1246, and has-miR-574-3p) from the results of microarray for RT
      qPCR validation. The results showed that expression level of miR-3646 in MDA-MB
      231/Doc cells was significantly higher than in MDA-MB-231/S cells. Compared to
      MCF-7/S cells, miR-3646 expression was up-regulated in MCF-7/Doc cells. Further
      studies revealed that transfection of miR-3646 mimics into MDA-MB-231/S or MCF
      7/S cells remarkably increased their drug resistance, in contrast, transfection
      of miR-3646 inhibitors into MDA-MB-231/Doc or MCF-7/Doc cells resulted in
      significant reduction of the drug resistance. By the pathway enrichment analyses
      for miR-3646, we found that GSK-3beta/beta-catenin signaling pathway was a
      significant pathway, in which GSK-3beta was an essential member. RT-qPCR and
      Western blot results demonstrated that miR-3646 could regulate GSK-3beta mRNA and
      protein expressions. Furthermore, a marked increase of both nuclear and
      cytoplasmic beta-catenin expressions (with phosphorylated-beta-catenin decrease)
      was observed in MDA-MB-231/Doc cells compared with MDA-MB-231/S cells, and their
      expression were positively related to miR-3646 and negatively correlated with GSK
      3beta. Taken together, our results suggest that miR-3646-mediated Doc resistance
      of breast cancer cells maybe, at least in part, through suppressing expression of
      GSK-3beta and resultantly activating GSK-3beta/beta-catenin signaling pathway. 

PMID- 27045587
TI  - Modeling Caribou Movements: Seasonal Ranges and Migration Routes of the Central
      Arctic Herd.
AB  - Migration is an important component of the life history of many animals, but
      persistence of large-scale terrestrial migrations is being challenged by
      environmental changes that fragment habitats and create obstacles to animal
      movements. In northern Alaska, the Central Arctic herd (CAH) of barren-ground
      caribou (Rangifer tarandus granti) is known to migrate over large distances, but
      the herd's seasonal distributions and migratory movements are not well
      documented. From 2003-2007, we used GPS radio-collars to determine seasonal
      ranges and migration routes of 54 female caribou from the CAH. We calculated
      Brownian bridges to model fall and spring migrations for each year and used the
      mean of these over all 4 years to identify areas that were used repeatedly.
      Annual estimates of sizes of seasonal ranges determined by 90% fixed kernel
      utilization distributions were similar between summer and winter (X = 27,929 SE =
      1,064 and X = 26,585 SE = 4912 km2, respectively). Overlap between consecutive
      summer and winter ranges varied from 3.3-18.3%. Percent overlap between summer
      ranges used during consecutive years (X = 62.4% SE = 3.7%) was higher than for
      winter ranges (X = 42.8% SE = 5.9%). Caribou used multiple migration routes each
      year, but some areas were used by caribou during all years, suggesting that these
      areas should be managed to allow for continued utilization by caribou. Restoring
      migration routes after they have been disturbed or fragmented is challenging.
      However, prior knowledge of movements and threats may facilitate maintenance of
      migratory paths and seasonal ranges necessary for long-term persistence of
      migratory species. 

PMID- 27045588
TI  - Epidemiology and Clinical Characteristics of Respiratory Infections Due to
      Adenovirus in Children Living in Milan, Italy, during 2013 and 2014.
AB  - To evaluate the predominant human adenovirus (HAdV) species and types associated
      with pediatric respiratory infections, nasopharyngeal swabs were collected from
      otherwise healthy children attending an emergency room in Milan, Italy, due to a
      respiratory tract infection from January 1 to February 28 of two subsequent
      years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel
      fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain
      reaction; their nucleotides were sequenced, and they were tested for positive
      selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV.
      HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in
      association with one other virus in 25 (41.0%) cases and with two or more viruses
      in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial
      virus were the most common co-infecting viral agents and were found in 12 (19.7%)
      and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed
      were highly conserved. In comparison to HAdV-negative children, those infected
      with HAdV had a reduced frequency of lower respiratory tract involvement (36.1%
      vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization
      (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were
      more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 +/-
      7,737 vs 9,565 +/- 3,211 cells/MUL; p = 0.04), respectively, in children infected
      by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by
      HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%)
      but difference did not reach statistical significant (p = 0.21). Children with
      high viral load were absent from child care attendance for a longer period of
      time (14.5 +/- 7.5 vs 5.5 +/- 3.2 days; p = 0.002) and had higher C reactive
      protein levels (41.3 +/- 78.5 vs 5.4 +/- 9.6 MUg/dL; p = 0.03). This study has
      shown that HAdV infections are diagnosed more commonly than usually thought and
      that HAdVs are stable infectious agents that do not frequently cause severe
      diseases. A trend toward more complex disease in cases due to HAdV species C and
      in those with higher viral load was demonstrated. However, further studies are
      needed to clarify factors contributing to disease severity to understand how to
      develop adequate preventive and therapeutic measures. 

PMID- 27045590
TI  - Postoperative Treatment of Pain after Hip Fracture in Elderly Patients with
      Dementia.
AB  - BACKGROUND/AIMS: Prior studies have shown that patients with dementia are at risk
      of receiving insufficient treatment for pain after a hip fracture. We therefore
      hypothesized that elderly hip fracture patients with dementia received less
      postoperative pain treatment than those without dementia. METHOD: All patients
      (age >=65 years) who had been operated on for a hip fracture in the Copenhagen
      University Hospital region in 2009 were included. Data about analgesic use for
      the first 72 h after surgery were acquired from the hospitals' electronic
      medication system and linked with information about dementia, comorbidity, and
      prior drug use. RESULTS: A total of 1,507 patients were included, of which 296
      (19.6%) suffered from dementia. Both groups were equally likely to receive
      paracetamol and opioids. Patients with dementia received lower doses of oral
      morphine equivalents during the first [dementia vs. no dementia: 29.0 (26.4-31.8)
      vs. 34.7 (33.1-36.4) mg, p = 0.001] and second [27.8 (25.4-30.5) vs. 31.2 (29.9
      32.4) mg, p = 0.019] but not on the third postoperative day (p = 0.10).
      CONCLUSION: The lower doses of opioids may reflect uncertainty about how to treat
      pain patients with dementia. Further guidance is needed, as inadequate treatment
      of pain may have adverse consequences.

PMID- 27045589
TI  - Co-Targeting of JNK and HUNK in Resistant HER2-Positive Breast Cancer.
AB  - Strategies for successful primary treatment of HER2-positive breast cancer
      include use of the HER2 inhibitors trastuzumab or lapatinib in combination with
      standard chemotherapy. While successful, many patients develop resistance to
      these HER2 inhibitors indicating an unmet need. Consequently, current research
      efforts are geared toward understanding mechanisms of resistance and the
      signaling modalities that regulate these mechanisms. We have undertaken a study
      to examine whether signaling molecules downstream of epidermal growth factor
      receptor, which often act as compensatory signaling outlets to circumvent HER2
      inhibition, can be co-targeted to overcome resistance. We identified JNK
      signaling as a potential area of intervention and now show that inhibiting JNK
      using the pan-JNK inhibitor, SP600125, is effective in the HER2-positive,
      resistant JIMT-1 xenograft mammary tumor model. We also investigate potential
      combination strategies to bolster the effects of JNK inhibition and find that co
      targeting of JNK and the protein kinase HUNK can prohibit tumor growth of
      resistant HER2-positive mammary tumors in vivo. 

PMID- 27045592
TI  - Flavobacterium aquicola sp. nov., isolated from river water.
AB  - A bacterial strain, designated TMd3a3T, was isolated from a freshwater sample
      collected from the Tamagawa River in Japan. The cells of strain TMd3a3T were
      facultatively anaerobic, Gram-stain-negative, non-spore-forming rods that showed
      gliding motility. This strain was capable of denitrification and anaerobic growth
      with nitrate. Cloned 16S rRNA gene sequences of strain TMd3a3T yielded three
      different sequences (similarity between the three sequences: 98.9-99.7 %). The
      16S rRNA gene sequences of strain TMd3a3T showed high similarity to those of
      Flavobacterium tructae 435-08T (97.2-97.4 % similarity), F. resistens BD-b365T
      (96.7-97.4 %), F. maotaiense T9T (97.0-97.3 %), F. limicola ST-82T (96.5-97.3 %),
      F. aquidurense WB 1.1-56T (96.9-97.2 %), F. spartansii T16T (96.9-97.2 %) and F.
      psychrolimnae LMG 22018T (96.4-97.0 %). Strain TMd3a3T contained menaquinone 6 as
      the sole respiratory quinone. The major cellular fatty acids were iso-C15 : 0 and
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c). The polar lipids were
      phosphatidylethanolamine, five unidentified aminolipids and five unidentified
      polar lipids. The DNA G+C content was 36.5 mol %. The DNA-DNA relatedness values
      of strain TMd3a3Twith F. tructae CCUG 60100T, F. resistens DSM 19382T, F.
      maotaiense JCM 19927T, F. limicola DSM 15094T, F. aquidurense DSM 18293T, F.
      spartansii ATCC BAA-2541T and F. psychrolimnae DSM 16141T were below 13 %. From
      the chemotaxonomic and physiological data and the levels of DNA-DNA relatedness,
      strain TMd3a3T should be classified as the representative of a novel species of
      the genus Flavobacterium, for which the name Flavobacterium aquicola sp. nov.
      (type strain TMd3a3T=JCM 30987T=DSM 100880T) is proposed. 

PMID- 27045591
TI  - Enhancing Beta-Catenin Activity via GSK3beta Inhibition Protects PC12 Cells
      against Rotenone Toxicity through Nurr1 Induction.
AB  - Parkinson's disease (PD) is characterized by progressive degeneration of
      dopaminergic (DA) neurons in the substantial nigra pars compacta. Increasing
      evidence showed that Wnt/beta-catenin pathway and the orphan nuclear receptor
      Nurr1 play crucial roles in the survival and functional maintenance of DA neurons
      in the midbrain and GSK-3beta antagonists LiCl and SB216763 were used to activate
      Wnt/beta-catenin pathway experimentally. However, the detail mechanism underlying
      the neuroprotection against apoptosis on DA neuron is still unclear and the
      interaction between Wnt/beta-catenin and Nurr1 remains undisclosed. In this
      study, using cell biological assay we investigated the function of Wnt/beta
      catenin and its crosstalk with Nurr1 on the course of PC12 cell degeneration in
      vitro. Our data showed that PC12 cell viability was inhibited by rotenone, but
      attenuated by GSK-3beta antagonists LiCl or SB216763. The activity of Wnt/beta
      catenin pathway was deregulated on exposure of rotenone in a concentration
      dependent manner. After the interference of beta-catenin with siRNA, LiCl or
      SB216763 failed to protect PC12 cells from apoptosis by the rotenone toxicity.
      Our data confirmed that Wnt/beta-catenin signaling activated by LiCl or SB216763
      enhanced Nurr1 expression to 2.75 +/- 0.55 and 4.06 +/- 0.41 folds respectively
      compared with control detected by real-time PCR and the interaction of beta
      catenin with Nurr1 was identified by co-immunoprecipitate analysis. In
      conclusion, the data suggested that Wnt/beta-catenin and Nurr1 are crucial
      factors in the survival of DA neurons, and the activation of Wnt/beta-catenin
      pathway exerts protective effects on DA neurons partly by mean of a co-active
      pattern with Nurr1. This finding may shed a light on the potential treatment of
      Parkinson disease. 

PMID- 27045593
TI  - GUIdock: Using Docker Containers with a Common Graphics User Interface to Address
      the Reproducibility of Research.
AB  - Reproducibility is vital in science. For complex computational methods, it is
      often necessary, not just to recreate the code, but also the software and
      hardware environment to reproduce results. Virtual machines, and container
      software such as Docker, make it possible to reproduce the exact environment
      regardless of the underlying hardware and operating system. However, workflows
      that use Graphical User Interfaces (GUIs) remain difficult to replicate on
      different host systems as there is no high level graphical software layer common
      to all platforms. GUIdock allows for the facile distribution of a systems biology
      application along with its graphics environment. Complex graphics based
      workflows, ubiquitous in systems biology, can now be easily exported and
      reproduced on many different platforms. GUIdock uses Docker, an open source
      project that provides a container with only the absolutely necessary software
      dependencies and configures a common X Windows (X11) graphic interface on Linux,
      Macintosh and Windows platforms. As proof of concept, we present a Docker package
      that contains a Bioconductor application written in R and C++ called networkBMA
      for gene network inference. Our package also includes Cytoscape, a java-based
      platform with a graphical user interface for visualizing and analyzing gene
      networks, and the CyNetworkBMA app, a Cytoscape app that allows the use of
      networkBMA via the user-friendly Cytoscape interface. 

PMID- 27045595
TI  - Innervation of sinoatrial nodal cells in the rabbit.
AB  - In spite of the fact that the rabbit is being widely used as a laboratory animal
      in experimental neurocardiology, neural control of SAN cells in the rabbit heart
      has been insufficiently examined thus far. This study analyzes the distribution
      of SAN cells and their innervation pattern employing fluorescent
      immunohistochemistry on rabbit whole mount atrial preparations. A dense network
      of adrenergic (positive for TH), cholinergic (positive for ChAT), nitrergic
      (positive for nNOS) and possibly sensory (positive for SP) NFs together with
      numerous neuronal somata were identified on the RRCV where the main mass of SAN
      cells positive for HCN4 were distributed as well. In general, the area occupied
      by SAN cells comprised nearly the entire RRCV and possessed a three to four times
      denser network of NFs compared with adjacent atrial walls. Adrenergic NFs
      predominated noticeably in-between SAN cells. Solitary neuronal somata or somata
      gathered into small clusters were positive solely for ChAT or nNOS, respectively
      or simultaneously for both neuronal markers (ChAT and nNOS). Neuronal somata
      positive for nNOS were more frequent than those positive for ChAT. In conclusion,
      findings of the present study demonstrate a dense and complex ganglionated neural
      network of both autonomic and sensory NFs, closely related to SAN cells which
      spread widely on the RRCV and extend as sleeves of these cells toward the walls
      of the rabbit RA. 

PMID- 27045594
TI  - Distinct forms of synaptic inhibition and neuromodulation regulate calretinin
      positive neuron excitability in the spinal cord dorsal horn.
AB  - The dorsal horn (DH) of the spinal cord contains a heterogenous population of
      neurons that process incoming sensory signals before information ascends to the
      brain. We have recently characterized calretinin-expressing (CR+) neurons in the
      DH and shown that they can be divided into excitatory and inhibitory
      subpopulations. The excitatory population receives high-frequency excitatory
      synaptic input and expresses delayed firing action potential discharge, whereas
      the inhibitory population receives weak excitatory drive and exhibits tonic or
      initial bursting discharge. Here, we characterize inhibitory synaptic input and
      neuromodulation in the two CR+ populations, in order to determine how each is
      regulated. We show that excitatory CR+ neurons receive mixed inhibition from
      GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive
      inhibition, which is dominated by glycine. Noradrenaline and serotonin produced
      robust outward currents in excitatory CR+ neurons, predicting an inhibitory
      action on these neurons, but neither neuromodulator produced a response in CR+
      inhibitory neurons. In contrast, enkephalin (along with selective mu and delta
      opioid receptor agonists) produced outward currents in inhibitory CR+ neurons,
      consistent with an inhibitory action but did not affect the excitatory CR+
      population. Our findings show that the pharmacology of inhibitory inputs and
      neuromodulator actions on CR+ cells, along with their excitatory inputs can
      define these two subpopulations further, and this could be exploited to modulate
      discrete aspects of sensory processing selectively in the DH.

PMID- 27045596
TI  - Peri-implant tissue behavior around non-titanium material: Experimental study in
      dogs.
AB  - The aim of this study is to assess the effectiveness of using non-titanium
      abutments for better establishment of peri-implant biological width and to assess
      the stability of the soft tissue. Forty-eight tapered dental titanium implants
      with internal connection of 3.5mm in diameter and 10mm length were implanted in
      post extraction alveoli of 6 dogs. Twenty-four abutments made in a reinforced
      polyetheretherketone (PEEK) formed the test group, and 24 titanium abutments, the
      control group. The groups were randomized. Histological, histomorphometric, ISQ
      and radiological analyses were performed. Greatest differences (control group vs.
      test group) were found at PM-Lc (Mucosa to lingual bone contact) (2.91+/-0.03 vs.
      3.71+/-0.18), and to PM Lingual-IS (2.65+/-0.43 vs. 3.57+/-0.38). Reinforced PEEK
      constitutes an effective alternative to conventional titanium abutments, given
      its high rate of biocompatibility, preservation of bone height and soft tissue
      stability. 

PMID- 27045597
TI  - Diaphragm: A vital respiratory muscle in mammals.
AB  - The diaphragm is a respiratory muscle that is primarily responsible for the
      respiratory function in normal individuals. In mammals, the diaphragm muscle has
      been studied from the early days of zoology, comparative and experimental
      anatomy, physiology, medicine, physics, and philosophy. However, even with these
      early advances in knowledge pertaining to the diaphragm, comprehensive
      morphological data on the diaphragm are still incomplete. In this review, we
      summarize the beginnings of the morphological description of the diaphragm, and
      we describe the current status of the known morphological and embryological
      features. In addition, we correlate how the impairment of the diaphragm muscle in
      Duchenne muscular dystrophy (DMD) can lead to patient deaths. DMD is the most
      common X-linked muscle degenerative disease and is caused by a lack of dystrophin
      protein. Dystrophin is an important muscle protein that links the cellular
      cytoskeleton with the extracellular matrix. In the absence of dystrophin, the
      muscle becomes susceptible to damage during muscle contraction. This review
      allows researchers to obtain an overview of the diaphragm, transcending the
      morphological data from animals described in conventional literature. 

PMID- 27045599
TI  - Clinical Biomechanics is expanding its focus!

PMID- 27045598
TI  - Sub-micron scale patterning of fluorescent silver nanoclusters using low-power
      laser.
AB  - Noble metal nanoclusters are ultrasmall nanomaterials with tunable properties and
      huge application potential; however, retaining their enhanced functionality is
      difficult as they readily lose their properties without stabilization. Here, we
      demonstrate a facile synthesis of highly photostable silver nanoclusters in a
      polymer thin film using visible light photoreduction. Furthermore, the different
      stages of the nanocluster formation are investigated in detail using absorption
      and fluorescence spectroscopy, fluorescence microscopy, and atomic force
      microscopy. A cost-effective fabrication of photostable micron-sized fluorescent
      silver nanocluster barcode is demonstrated in silver-impregnated polymer films
      using a low-power continuous-wave laser diode. It is shown that a laser power of
      as low as 0.75 mW is enough to write fluorescent structures, corresponding to the
      specifications of a commercially available laser pointer. The as-formed
      nanocluster-containing microstructures can be useful in direct labeling
      applications such as authenticity marking and fluorescent labeling. 

PMID- 27045600
TI  - Integration of acetylenic carbon clusters and silver clusters: template synthesis
      and stability enhancement.
AB  - Three silver cluster complexes were synthesized with carbon network ligands as
      inner templates, including [(C=C)2C=C(C=C)2](4-), [C6(C=C)6](6-) and
      [C6H(C=C)5](5-). The resulting clusters 1-3 have been characterized by X-ray
      crystallography and other techniques. This study showcases a promising
      methodology to acquire intricate all-carbon units and provides a platform to
      investigate their chemistry.

PMID- 27045601
TI  - 5-Aminolevulinic Acid Photodynamic Therapy combined with CO2 laser therapy in
      treatment of laryngeal papilloma: Case report.
AB  - This article describes the case of 5-Aminolevulinic Acid Photodynamic Therapy
      (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with
      CO2 Laser Therapy in the treatment of three patients with juvenile laryngeal
      papilloma. Laryngeal papilloma Clinically, it features rapid growth, multi-focus,
      frequent recurrence and possibility of spreading to the lower respiratory tract.
      ALA-PDT via self-retaining laryngoscope under general anesthesia combined with
      CO2 Laser Therapy is safe and effective for clearing laryngeal papilloma,
      laryngeal papilloma was fully removed from the three patients, with no recurrence
      during the 6-24 months of follow-up medical examination. 5-Aminolevulinic Acid
      Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general
      anesthesia combined with CO2 Laser can be used for treating laryngeal papilloma. 

PMID- 27045602
TI  - Does Carbohydrate Intake During Endurance Running Improve Performance? A Critical
      Review.
AB  - Wilson, PB. Does carbohydrate intake during endurance running improve
      performance? A critical review. J Strength Cond Res 30(12): 3539-3559, 2016
      Previous review articles assessing the effects of carbohydrate ingestion during
      prolonged exercise have not focused on running. Given the popularity of distance
      running and the widespread use of carbohydrate supplements, this article reviewed
      the evidence for carbohydrate ingestion during endurance running. The criteria
      for inclusion were (a) experimental studies reported in English language
      including a performance task, (b) moderate-to-high intensity exercise >60 minutes
      (intermittent excluded), and (c) carbohydrate ingestion (mouth rinsing excluded).
      Thirty studies were identified with 76 women and 505 men. Thirteen of the 17
      studies comparing a carbohydrate beverage(s) with water or a placebo found a
      between-condition performance benefit with carbohydrate, although heterogeneity
      in protocols precludes clear generalizations about the expected effect sizes.
      Additional evidence suggests that (a) performance benefits are most likely to
      occur during events >2 hours, although several studies showed benefits for tasks
      lasting 90-120 minutes; (b) consuming carbohydrate beverages above ad libitum
      levels increases gastrointestinal discomfort without improving performance; (c)
      carbohydrate gels do not influence performance for events lasting 16-21 km; and
      (d) multiple saccharides may benefit events >2 hours if intake is >=1.3 g.min
      Given that most participants were fasted young men, inferences regarding women,
      adolescents, older runners, and those competing in fed conditions are hampered.
      Future studies should address these limitations to further elucidate the role of
      carbohydrate ingestion during endurance running.

PMID- 27045603
TI  - Ganoderma lucidum (Reishi mushroom) for cancer treatment.
AB  - BACKGROUND: Ganoderma lucidum is a natural medicine that is widely used and
      recommended by Asian physicians and naturopaths for its supporting effects on
      immune system. Laboratory research and a handful of preclinical trials have
      suggested that G. lucidum carries promising anticancer and immunomodulatory
      properties. The popularity of taking G. lucidum as an alternative medicine has
      been increasing in cancer patients. However, there is no systematic review that
      has been conducted to evaluate the actual benefits of G. lucidum in cancer
      treatment. OBJECTIVES: To evaluate the clinical effects of G. lucidum on long
      term survival, tumour response, host immune functions and quality of life in
      cancer patients, as well as adverse events associated with its use. SEARCH
      METHODS: We searched an extensive set of databases including the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI,
      CMCC and VIP Information/Chinese Scientific Journals Database was searched for
      randomised controlled trials (RCTs) in October 2011. Other strategies used were
      scanning the references of articles retrieved, handsearching of the International
      Journal of Medicinal Mushrooms and contact with herbal medicine experts and
      manufacturers of G. lucidum. For this update we updated the searches in February
      2016. SELECTION CRITERIA: To be eligible for being included in this review,
      studies had to be RCTs comparing the efficacy of G. lucidum medications to active
      or placebo control in patients with cancer that had been diagnosed by pathology.
      All types and stages of cancer were eligible for inclusion. Trials were not
      restricted on the basis of language. DATA COLLECTION AND ANALYSIS: Five RCTs met
      the inclusion criteria and were included in this review. Two independent review
      authors assessed the methodological quality of individual trials. Common primary
      outcomes were tumour response evaluated according to the World Health
      Organization (WHO) criteria, immune function parameters such as natural killer
      (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life
      measured by the Karnofsky scale score. No trial had recorded long-term survival
      rates. Associated adverse events were reported in one study. A meta-analysis was
      performed to pool available data from the primary trials. Results were gauged
      using relative risks (RR) and standard mean differences (SMD) for dichotomous and
      continuous data respectively, with a 95% confidence interval (CI). MAIN RESULTS:
      The methodological quality of primary studies was generally unsatisfying and the
      results were reported inadequately in many aspects. Additional information was
      not available from primary trialists. The meta-analysis results showed that
      patients who had been given G. lucidum alongside with chemo/radiotherapy were
      more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50;
      95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate
      the same regression rate as that seen in combined therapy. The results for host
      immune function indicators suggested that G. lucidum simultaneously increases the
      percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05%
      (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03),
      respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were
      marginally elevated. Four studies showed that patients in the G. lucidum group
      had relatively improved quality of life in comparison to controls. One study
      recorded minimal side effects, including nausea and insomnia. No significant
      haematological or hepatological toxicity was reported. AUTHORS' CONCLUSIONS: Our
      review did not find sufficient evidence to justify the use of G. lucidum as a
      first-line treatment for cancer. It remains uncertain whether G. lucidum helps
      prolong long-term cancer survival. However, G. lucidum could be administered as
      an alternative adjunct to conventional treatment in consideration of its
      potential of enhancing tumour response and stimulating host immunity. G. lucidum
      was generally well tolerated by most participants with only a scattered number of
      minor adverse events. No major toxicity was observed across the studies. Although
      there were few reports of harmful effect of G. lucidum, the use of its extract
      should be judicious, especially after thorough consideration of cost-benefit and
      patient preference. Future studies should put emphasis on the improvement in
      methodological quality and further clinical research on the effect of G. lucidum
      on cancer long-term survival are needed. An update to this review will be
      performed every two years.

PMID- 27045604
TI  - Regimens of fetal surveillance of suspected large-for-gestational-age fetuses for
      improving health outcomes.
AB  - BACKGROUND: Policies and protocols vary widely for fetal surveillance in a
      pregnancy where the fetus is suspected to be large-for-gestational-age (LGA). All
      ultimately culminate in decisions about the mode and timing of birth. LGA is
      known to be associated with increased risks to both the mother and baby.
      Interventions based on surveillance regimen findings may be associated with risks
      to the mother and baby. OBJECTIVES: To assess the effectiveness or efficacy of
      different antenatal surveillance methods for the suspected LGA fetus on important
      health outcomes for the mother and baby. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (30 August 2015),
      ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform
      (ICTRP) (21 August 2015). SELECTION CRITERIA: Published and unpublished
      randomised, quasi-randomised and cluster-randomised trials comparing the effects
      of described antenatal fetal surveillance regimens for women with suspected LGA
      infants. DATA COLLECTION AND ANALYSIS: We identified no studies that met the
      inclusion criteria for this review. MAIN RESULTS: There are no included trials.
      AUTHORS' CONCLUSIONS: We found no randomised controlled trials that assessed the
      effect of antenatal fetal surveillance regimens of a suspected LGA fetus on
      important health outcomes for the mother and baby.There has been a rise in the
      prevalence of LGA babies over the past few decades in many countries. Research is
      therefore required on regimens of antenatal surveillance of suspected LGA
      infants, in order to guide practice and improve the health outcomes for the
      mother and infant. In particular, randomised control trials to investigate
      whether serial antenatal clinic and ultrasound assessments of suspected LGA
      infants (including liquor volume and markers of fetal adiposity) would be useful,
      to assess whether surveillance methods improve health outcomes. In addition, as
      there are concerns that identifying suspected LGA fetuses may lead to unnecessary
      maternal anxiety, investigations and interventions, any such trial would need to
      assess the risks as well as benefits of regimens of fetal surveillance for
      suspected LGA fetuses.

PMID- 27045605
TI  - Neuroradiology Using Secure Mobile Device Review.
AB  - BACKGROUND: Image review on computer-based workstations has made film-based
      review outdated. Despite advances in technology, the lack of portability of
      digital workstations creates an inherent disadvantage. As such, we sought to
      determine if the quality of image review on a handheld device is adequate for
      routine clinical use. METHODS: Six CT/CTA cases and six MR/MRA cases were
      independently reviewed by three neuroradiologists in varying environments: high
      and low ambient light using a handheld device and on a traditional imaging
      workstation in ideal conditions. On first review (using a handheld device in high
      ambient light), a preliminary diagnosis for each case was made. Upon changes in
      review conditions, neuroradiologists were asked if any additional features were
      seen that changed their initial diagnoses. Reviewers were also asked to comment
      on overall clinical quality and if the handheld display was of acceptable quality
      for image review. RESULTS: After the initial CT review in high ambient light,
      additional findings were reported in 2 of 18 instances on subsequent reviews.
      Similarly, additional findings were identified in 4 of 18 instances after the
      initial MR review in high ambient lighting. Only one of these six additional
      findings contributed to the diagnosis made on the initial preliminary review.
      CONCLUSIONS: Use of a handheld device for image review is of adequate diagnostic
      quality based on image contrast, sharpness of structures, visible artefacts and
      overall display quality. Although reviewers were comfortable with using this
      technology, a handheld device with a larger screen may be diagnostically
      superior.

PMID- 27045606
TI  - BM ageing: Implication for cell therapy with EPCs.
AB  - The bone marrow (BM) is a well-recognized source of stem/progenitor cells for
      cell therapy in cardiovascular diseases (CVDs). Preclinical and clinical studies
      suggest that endothelial progenitor cells (EPCs) contribute to reparative process
      of vascular endothelium and participate in angiogenesis. As for all organs and
      cells across the lifespan, BM and EPCs are negatively impacted by ageing due to
      microenvironment modifications and EPC progressive dysfunctions. The encouraging
      results in terms of neovascularization observed in young animals after EPC
      administration were mitigated in aged patients treated for ischemic CVDs. The
      limited efficacy of EPC-based therapy in clinical setting might be ascribed at
      least partly to ageing. In this review, we comprehensively discussed the age
      related changes of BM and EPCs and their implication for cardiovascular cell
      therapies. Finally, we examined alternative approaches under investigation to
      enhance EPC potency.

PMID- 27045607
TI  - Complement receptor immunoglobulin: a control point in infection and immunity,
      inflammation and cancer.
AB  - The B7 family-related protein, V-set and Ig domain (VSIG4) / Z39Ig / complement
      receptor immunoglobulin (CRIg), is a new player in the regulation of immunity to
      infection and inflammation. The unique features of this receptor as compared with
      classical complement receptors, CR3 and CR4, have heralded the emergence of new
      concepts in the regulation of innate and adaptive immunity. Its selective
      expression in tissue macrophages and dendritic cells has been considered of
      importance in host defence and in maintaining tolerance against self-antigens.
      Although a major receptor for phagocytosis of complement opsonised bacteria, its
      array of emerging functions which incorporates the immune suppressive and anti
      inflammatory action of the receptor have now been realised. Accumulating evidence
      from mouse experimental models indicates a potential role for CRIg in protection
      against bacterial infection and inflammatory diseases, such as rheumatoid
      arthritis, type 1 diabetes and systemic lupus erythematosus, and also in
      promotion of tumour growth. CRIg expression can be considered as a control point
      in these diseases, through which inflammatory mediators, including cytokines,
      act. The ability of CRIg to suppress cytotoxic T cell proliferation and function
      may underlie its promotion of cancer growth. Thus, the unique properties of this
      receptor open up new avenues for understanding of the pathways that regulate
      inflammation during infection, autoimmunity and cancer with the potential for new
      drug targets to be identified. While some complement receptors may be differently
      expressed in mice and humans, as well as displaying different properties, mouse
      CRIg has a structure and function similar to the human receptor, suggesting that
      extrapolation to human diseases is appropriate. Furthermore, there is emerging
      evidence in human conditions that CRIg may be a valuable biomarker in infection
      and immunity, inflammatory conditions and cancer prognosis.

PMID- 27045609
TI  - Dynamic RSA: Examining parasympathetic regulatory dynamics via vector
      autoregressive modeling of time-varying RSA and heart period.
AB  - Expanding on recently published methods, the current study presents an approach
      to estimating the dynamic, regulatory effect of the parasympathetic nervous
      system on heart period on a moment-to-moment basis. We estimated second-to-second
      variation in respiratory sinus arrhythmia (RSA) in order to estimate the
      contemporaneous and time-lagged relationships among RSA, interbeat interval
      (IBI), and respiration rate via vector autoregression. Moreover, we modeled these
      relationships at lags of 1 s to 10 s, in order to evaluate the optimal latency
      for estimating dynamic RSA effects. The IBI (t) on RSA (t-n) regression parameter
      was extracted from individual models as an operationalization of the regulatory
      effect of RSA on IBI-referred to as dynamic RSA (dRSA). Dynamic RSA positively
      correlated with standard averages of heart rate and negatively correlated with
      standard averages of RSA. We propose that dRSA reflects the active downregulation
      of heart period by the parasympathetic nervous system and thus represents a novel
      metric that provides incremental validity in the measurement of autonomic cardiac
      control-specifically, a method by which parasympathetic regulatory effects can be
      measured in process.

PMID- 27045608
TI  - Engineered kinesin motor proteins amenable to small-molecule inhibition.
AB  - The human genome encodes 45 kinesin motor proteins that drive cell division, cell
      motility, intracellular trafficking and ciliary function. Determining the
      cellular function of each kinesin would benefit from specific small-molecule
      inhibitors. However, screens have yielded only a few specific inhibitors. Here we
      present a novel chemical-genetic approach to engineer kinesin motors that can
      carry out the function of the wild-type motor yet can also be efficiently
      inhibited by small, cell-permeable molecules. Using kinesin-1 as a prototype, we
      develop two independent strategies to generate inhibitable motors, and
      characterize the resulting inhibition in single-molecule assays and in cells. We
      further apply these two strategies to create analogously inhibitable kinesin-3
      motors. These inhibitable motors will be of great utility to study the functions
      of specific kinesins in a dynamic manner in cells and animals. Furthermore, these
      strategies can be used to generate inhibitable versions of any motor protein of
      interest. 

PMID- 27045610
TI  - Chronic recurrent abdominal pain as a result of arcuate ligament syndrome.

PMID- 27045611
TI  - Surgical alternatives in the treatment of portal vein thrombosis in liver
      transplantation.

PMID- 27045612
TI  - Previous radial artery catheterization complicates invasive monitoring during
      cardiac surgery.

PMID- 27045613
TI  - Jaundice secondary to a simple liver cyst with traumatic intracystic hemorrhage.

PMID- 27045614
TI  - Is pancreaticoduodenectomy a safe procedure in the cirrhotic patient?
AB  - INTRODUCTION: Pancreaticoduodenectomy (PD) is usually contraindicated in chronic
      liver disease. The objective of the present study was to analyze PD results in
      cirrhotic patients, and compare them with non-cirrhotic ones. METHODS: Between
      1994 and 2014 we prospectively collected all patients with a PD for periampullar
      neoplasms in Hospital Universitari de Bellvitge. We registered preoperative,
      intraoperative and postoperative variables. We defined patients undergoing PD
      with liver cirrhosis as the study group (CH group), and those without liver
      cirrhosis as the control group (NCH group). A case/control study was performed
      (1/2). RESULTS: We registered 15 patients in the CH group, all with good liver
      function (Child A), and included 30 patients in NCH group. The causes of
      hepatopathy were HCV (60%) and alcoholism (40%). For the 3 moments studied, the
      CH group had a lower blood platelet count and a higher prothrombin ratio,
      compared with NCH group. Postoperative morbidity was 60% and mean postoperative
      stay was 25+/-19 days, with no differences in terms of complications between CH
      group and NCG group (73% vs. 53%, P=.1). Presence of ascites was higher in the CH
      group compared with NCH group (28 vs. 0%, P<.001). There were no differences in
      terms of hemorrhage or pancreatic fistula. Four patients of the CH group and 2
      patients of the NCH group were reoperated on (26.7 vs. 6.7%, P=.1). There was no
      postoperative mortality. CONCLUSIONS: PD is a safe procedure in cirrhotic
      patients with good liver function although it presents high morbidity.

PMID- 27045615
TI  - Validation of a High-Throughput Screening Assay for Identification of Adjunctive
      and Directly Acting Antimicrobials Targeting Carbapenem-Resistant
      Enterobacteriaceae.
AB  - We describe development and validation of a high-throughput screen (HTS) for
      identifying small molecules that restore the efficacy of carbapenems
      (adjunctives) and/or directly inhibit growth of carbapenem-resistant
      Enterobacteriaceae (CRE). Our HTS assay is based on a screen-counterscreen
      approach using a representative multidrug-resistant CRE strain, Klebsiella
      pneumoniae BIDMC12A. Specifically, we tested the ability of small molecules to
      inhibit bacterial growth in the presence (screen) or absence (counterscreen) of
      meropenem, a representative carbapenem antibiotic. Primary screening of 11,698
      known bioactive compounds identified 14 with adjunctive activity and 79 with
      direct antimicrobial effect. Secondary screening identified triclosan as a
      strongly synergistic meropenem adjunctive (fractional inhibitory concentration =
      0.48) and confirmed azidothymidine (AZT) (minimal inhibitory concentration [MIC]
      = 4 MUg mL(-1)), NH125 (MIC = 4 MUg mL(-1)), diphenyleneiodonium chloride (MIC =
      8 MUg mL(-1)), and spectinomycin (MIC = 32 MUg mL(-1)) as potent direct
      antimicrobials. Spectrum of activity of AZT and spectinomycin was tested against
      a collection of 103 representative Enterobacteriaceae strains (~50% CRE). AZT, a
      nucleoside analog used to treat human immunodeficiency virus, demonstrated an
      MIC50 of 2 MUg mL(-1). Spectinomycin, an antibiotic used to treat gonorrhea, had
      an MIC50 of 32 MUg mL(-1). Therefore, a significant percentage of CRE strains
      appeared relatively susceptible to these antimicrobials. These data identified
      AZT and spectinomycin as available agents warranting further study for potential
      treatment of multidrug-resistant CRE infection. Our results provide proof of
      principle and impetus for performing a large-scale HTS for discovery of novel,
      small-molecule adjunctives and antibacterial agents directly targeting CRE. 

PMID- 27045616
TI  - Origin and Dynamics of Rare Earth Elements during Flood Events in Contaminated
      River Basins: Sr-Nd-Pb Isotopic Evidence.
AB  - In order to precisely quantify the contribution of anthropogenic activities and
      geogenic sources to the dissolved and suspended loads of rivers we have combined
      for the first time Rare Earth Element (REE) concentrations with Sr-Nd-Pb isotope
      ratios. We observed enrichments in Anthropogenic Rare Earth Elements (AREE) for
      dissolved (Gd) and suspended (Ce and Nd) loads of river water. During flood
      events, AREE anomalies progressively disappeared and gave way to the geogenic
      chemical signature of the basin in both dissolved and suspended loads. The
      isotopic data confirm these observations and shed new light on the trace elements
      sources. On the one hand, dissolved loads have peculiar isotopic characteristics
      and carry mainly limestone-derived and anthropogenic Sr and Nd as well as
      significant amounts of anthropogenic Pb. On the other hand, the results clearly
      indicate that anthropogenic contributions impact the suspended loads in all
      hydrological conditions. This study demonstrates that anthropogenic contributions
      to the river may change not only Pb but also Sr and Nd isotopic compositions in
      both dissolved and suspended loads. This is of importance for future provenance
      studies.

PMID- 27045617
TI  - Primary non-Hodgkin lymphoma of the uterine cervix of a follicular type - case
      report.

PMID- 27045618
TI  - Comparison of Eight Equations That Predict Percent Body Fat Using Skinfolds in
      American Youth.
AB  - BACKGROUND: Skinfolds are often used in equations to predict percent body fat
      (PBF) in youth. Although there are numerous such equations published, there is
      limited information to help researchers determine which equation to use for their
      sample. METHODS: Using data from the 1999-2006 National Health and Nutrition
      Examination Surveys (NHANES), we compared eight published equations for
      prediction of PBF. These published equations all included triceps and/or
      subscapular skinfold measurements. We examined the PBF equations in a nationally
      representative sample of American youth that was matched by age, sex, and
      race/ethnicity to the original equation development population and a full sample
      of 8- to 18-year-olds. We compared the equation-predicted PBF to the dual
      emission X-ray absorptiometry (DXA)-measured PBF. The adjusted R(2), root mean
      square error (RMSE), and mean signed difference (MSD) were compared. The MSDs
      were used to examine accuracy and differential bias by age, sex, and
      race/ethnicity. RESULTS: When applied to the full range of 8- 18-year-old youth,
      the R(2) values ranged from 0.495 to 0.738. The MSD between predicted and DXA
      measured PBF indicated high average accuracy (MSD between -1.0 and 1.0) for only
      three equations (Bray subscapular equation and Dezenberg equations [with and
      without race/ethnicity]). The majority of the equations showed differential bias
      by sex, race/ethnicity, weight status, or age. CONCLUSIONS: These findings
      indicate that investigators should use caution in the selection of an equation to
      predict PBF in youth given that results may vary systematically in important
      subgroups.

PMID- 27045619
TI  - Alkyl-Based Surfactants at a Liquid Mercury Surface: Computer Simulation of
      Structure, Self-Assembly, and Phase Behavior.
AB  - Self-assembled organic films on liquid metals feature a very rich phase behavior,
      which qualitatively differs from the one on crystalline metals. In contrast to
      conventional crystalline supports, self-assembled alkylthiol monolayers on liquid
      metals possess a considerably higher degree of molecular order, thus enabling
      much more robust metal-molecule-semiconductor couplings for organic electronics
      applications. Yet, compared to crystalline substrates, the self-assembly of
      organic surfactants on liquid metals has been studied to a much lesser extent. In
      this Letter we report the first of its kind molecular simulation investigation of
      alkyl-based surfactants on a liquid mercury surface. The focus of our
      investigation is the surfactant conformations as a function of surface coverage
      and surfactant type. First, we consider normal alkanes because these systems set
      the basis for simulations of all other organic surfactants on liquid mercury.
      Subsequently, we proceed with the discussion of alkylthiols that are the most
      frequently used surfactants in the surface science of hybrid organometallic
      interfaces. Our results indicate a layering transition of normal alkanes as well
      as alkylthiols from an essentially bare substrate to a completely filled
      monolayer of laying molecules. As the surface coverage increases further, we
      observe a partial wetting of the laying monolayer by the bulk phase of alkanes.
      In the case of alkylthiols, we clearly see the coexistence of molecules in laying
      down and standing-up conformations, in which the sulfur headgroups of the thiols
      are chemically bound to mercury. In the standing-up phase, the headgroups form an
      oblique lattice. For the first time we were able to explicitly characterize the
      molecular-scale structure and transitions between phases of alkyl-based
      surfactants and to demonstrate how the presence of a thiol headgroup
      qualitatively changes the phase equilibrium and structure in these systems. The
      observed phenomena are consistent with available direct and indirect experimental
      evidence. 

PMID- 27045620
TI  - Biochar amendment reduced methylmercury accumulation in rice plants.
AB  - There is growing concern about methylmercury (MeHg) accumulation in rice grains
      and thus enhanced dietary exposure to MeHg in Asian countries. Here, we explored
      the possibility of reducing grain MeHg levels by biochar amendment, and the
      underlying mechanisms. Pot (i.e., rice cultivation in biochar amended soils) and
      batch experiments (i.e., incubation of amended soils under laboratory conditions)
      were carried out, to investigate MeHg dynamics (i.e., MeHg production,
      partitioning and phytoavailability in paddy soils, and MeHg uptake by rice) under
      biochar amendment (1-4% of soil mass). We demonstrate for the first time that
      biochar amendment could evidently reduce grain MeHg levels (49-92%). The declines
      could be attributed to the combined effects of: (1) increased soil MeHg
      concentrations, probably explained by the release of sulfate from biochar and
      thus enhanced microbial production of MeHg (e.g., by sulfate-reducing bacteria),
      (2) MeHg immobilization in soils, facilitated by the large surface areas and high
      organosulfur content of biochar, and (3) biodilution of MeHg in rice grains, due
      to the increased grain biomass under biochar amendment (35-79%). These
      observations together with mechanistic explanations improve understanding of MeHg
      dynamics in soil-rice systems, and support the possibility of reducing MeHg
      phytoaccumulation under biochar amendment.

PMID- 27045621
TI  - Influence of microwaves on the leaching kinetics of uraninite from a low grade
      ore in dilute sulfuric acid.
AB  - This paper describes a study on microwave assisted leaching of uranium from a low
      grade ore of Indian origin. The host rock for uranium mineralization is chlorite
      biotite-muscovite-quartzo-feldspathic schist. The dominant presence of siliceous
      minerals determined leaching of uranium values in sulfuric acid medium under
      oxidizing conditions. Process parametric studies like the effect of sulfuric acid
      concentration (0.12-0.50M), redox potential (400-500mV), particle size (600
      300MUm) and temperature (35 degrees -95 degrees C) indicated that microwave
      assisted leaching is more efficient in terms of overall uranium dissolution,
      kinetics and provide relatively less impurities (Si, Al, Mg and Fe) in the leach
      liquor compared to conventional conductive leaching. The kinetics of leaching
      followed shrinking core model with product layer diffusion as controlling
      mechanism.

PMID- 27045622
TI  - Low dose perfluorooctanoate exposure promotes cell proliferation in a human non
      tumor liver cell line.
AB  - Perfluorooctanoate (PFOA) is a well-known persistent organic pollutant widely
      found in the environment, wildlife and humans. Medical surveillance and
      experimental studies have investigated the potential effects of PFOA on human
      livers, but the hepatotoxicity of PFOA on humans and its underlying mechanism
      remain to be clarified. We exposed a human liver cell line (HL-7702) to 50MUM
      PFOA for 48h and 96h, and identified 111 significantly differentially expressed
      proteins by iTRAQ analysis. A total of 46 proteins were related to cell
      proliferation and apoptosis. Through further analysis of the cell cycle,
      apoptosis and their related proteins, we found that low doses of PFOA (50-100MUM)
      promoted cell proliferation and numbers by promoting cells from the G1 to S
      phases, whereas high doses of PFOA (200-400MUM) led to reduced HL-7702 cell
      numbers compared with that of the control mainly due to cell cycle arrest in the
      G0/G1 phase. To our knowledge, this is the first report on the promotion of cell
      cycle progression in human cells following PFOA exposure.

PMID- 27045623
TI  - Ruthenium recovery from acetic acid industrial effluent using chemically stable
      and high-performance polyethylenimine-coated polysulfone-Escherichia coli biomass
      composite fibers.
AB  - Recovery of precious metal ions from waste effluents is of high concern. In
      general, ruthenium (Ru) is used in the Cativa process as promoter for
      carbonylation catalyst and discharged into acetic acid effluent. In the present
      work, we have designed and developed polyethylenimine-coated polysulfone
      bacterial biomass composite fiber (PEI-PSBF) to recover Ru from industrial
      effluent. The sorbent was manufactured by electrostatic attachment of
      polyethylenimine (PEI) to the surface of polysulfone-biomass composite fiber
      (PSBF), which was prepared through spinning of the mixture of polysulfone and
      Escherichia coli biomass in N,N-dimethylformamide (DMF) into water. Developed PEI
      PSBF was highly stable in the acetic acid effluent. The maximum sorption capacity
      of the developed sorbent PEI-PSBF, coated with PEI (with M.W. of 75,000), was
      121.28+/-13.15mg/g, which was much higher than those of ion exchange resins,
      TP214, Amberjet 4200, and M500. The PEI-PSBF could be successfully applied in the
      flow-through column system, showing 120 beds of breakthrough volume.

PMID- 27045624
TI  - Reconfigurable OR and XOR logic gates based on dual responsive on-off-on
      micromotors.
AB  - In this study, we report a hemisphere-like micromotor. Intriguingly, the
      micromotor exhibits controllable on-off-on motion, which can be actuated by two
      different external stimuli (UV and NH3). Moreover, the moving direction of the
      micromotor can be manipulated by the direction in which UV and NH3 are applied.
      As a result, the motion accelerates when both stimuli are applied in the same
      direction and decelerates when the application directions are opposite to each
      other. More interestingly, the dual stimuli responsive micromotor can be utilized
      as a reconfigurable logic gate with UV and NH3 as the inputs and the motion of
      the micromotor as the output. By controlling the direction of the external
      stimuli, OR and XOR dual logic functions can be realized. 

PMID- 27045625
TI  - Presence of Mycoplasma agalactiae in semen of naturally infected asymptomatic
      rams.
AB  - The purpose of the present study was to assess the presence of Mycoplasma
      agalactiae (Ma), the main causative agent of ovine contagious agalactia (CA), in
      semen of naturally infected rams. Therefore, semen samples from 167 rams residing
      in three different artificial insemination (AI) centers of a CA-endemic area were
      studied by microbiological and molecular techniques. In addition, serial
      ejaculates from the same rams were evaluated to determine the excretion dynamics
      of Ma. Of the 384 samples studied, Ma was detected in 56 (14.58%) which belonged
      to 44 different rams (26.35%). These findings confirm the ability of Ma to be
      excreted in semen of asymptomatic rams. Furthermore, these results also evidence
      the presence of these asymptomatic carriers of Ma in ovine AI centers,
      representing a serious health risk regarding the spread and maintenance of CA,
      especially in endemic areas. Moreover, the excretion of Ma in semen also points
      to the risk of venereal transmission of this disease. The current results
      highlight the need to implement control measures to prevent the admission of
      infected rams in AI centers and the necessity to continuously monitor semen
      samples to effectively detect infected individuals. 

PMID- 27045626
TI  - Andrology laboratory review: Evaluation of sperm concentration.
AB  - This article is the result of the work of the andrology task-force of the
      Association of Applied Animal Andrology, American College of Theriogenologists,
      European College of Animal Reproduction, Society for Theriogenology, and National
      Association of Animal Breeders. It is intended to serve as a comprehensive
      reference on methods to evaluate sperm concentration and to contribute to the
      adoption of best practices in veterinary andrology laboratories. The information
      covered in the article includes sample preparation and the use of manual counts,
      spectrophotometers, computer-assisted semen analysis, NucleoCounter, and flow
      cytometry. Emphasis is given to the principles of the methods and equipment,
      performing the evaluation, and common mistakes and/or pitfalls. In addition, the
      precision and accuracy of the different methods are also discussed. 

PMID- 27045627
TI  - Recovery of normal testicular temperature after scrotal heat stress in rams
      assessed by infrared thermography and its effects on seminal characteristics and
      testosterone blood serum concentration.
AB  - Reestablishment of testicular normal temperature after testicular heat stress is
      unknown and its effect varies widely. The aim of this study was to investigate
      the impact of scrotal insulation (IN) on testicular temperature and its relation
      to semen quality and testosterone blood serum concentration. For this, 33 rams
      were used; 17 submitted to IN for 72 hours (using bags involving the testes) and
      16 not submitted to IN (control group). The experiment was performed between
      August and December 2013 in Pirassununga, Brazil (21 degrees 56"13" South/47
      degrees 28'24" West). Seminal characteristics, testosterone blood serum
      concentration, rectal temperature (RT), respiratory frequency, scrotal
      superficies mean temperature (SSMT), and eye area mean temperature (EAMT) were
      analyzed 7 days before IN and 21, 35, 49, 63, and 90 days afterward. Scrotal
      superficies mean temperature and EAMT were measured by thermography camera FLIR
      T620. Testosterone was evaluated by radioimmunoassay. Analysis of variance was
      used to determine the main effects of treatment, time, and treatment-by-time
      interaction using PROC MIXED of SAS software adding command REPEAT. Pearson
      correlation test was used to verify correlation between SSMT, EAMT, RT, and
      respiratory frequency. Significant difference was considered when P <= 0.05. At
      the end of IN, SSMT was higher (P < 0.05) in insulated group (32.26 +/- 0.19(o)C)
      than in control group (30.58 +/- 0.18(o)C), and the difference between rectal and
      testicular (deduced from SSMT) temperatures was 1.12  degrees C; in the other
      times of the evaluation this difference was between 2.91 and 4.25  degrees C in
      IN group. Scrotal superficies mean temperature was reestablished 24 hours after
      IN. Rectal temperature and EAMT presented correlation (r = 0.59; P < 0.0001).
      There was time-by-treatment interaction for total sperm (P = 0.0038) and
      progressive motility (P = 0.01), abnormal spermatozoa (P < 0.0001), membranes
      integrity (P < 0.0001), induced thiobarbituric acid reactive substances (TBARSs;
      P = 0.05), and DNA integrity (P = 0.0004). These semen characteristics were
      negatively affected 21 days after IN, and excluding induced TBARSs and
      abnormalities, recovered 35 days afterward; induced TBARSs just were affected
      after 49 days of IN; sperm abnormalities just recovered after 63 days.
      Testosterone blood serum concentration was lesser in insulated rams (P = 0.03).
      Thus, the difference of 1.12  degrees C between RT and testicular temperature
      impacts semen quality and testosterone blood serum concentration. Moreover, this
      study shows that rams can recover testes temperature efficiently toward IN and
      that infrared thermography is an efficient tool to identify differences on SSMT. 

PMID- 27045628
TI  - Estrous synchronization strategies to optimize beef heifer reproductive
      performance after reproductive tract scoring.
AB  - Three experiments comparing four estrous synchronization protocols were conducted
      to determine estrous expression rate and artificial insemination pregnancy rate
      (AI-PR) in heifers with a range (1-5) of reproductive tract scores (RTSs). At
      enrollment (Day 0), 1783 Angus cross beef heifers from six locations were given
      body condition score and RTS. The four protocols were: (1) HRTS-DPGF group
      heifers with RTS 5 received prostaglandin F2alpha (PGF; Dinoprost 25 mg; im) on
      Days 0 and 14; (2) HRTS-CIDR-PGF group-heifers with RTS 5 received a CIDR (1.3-g
      progesterone) insert on Day 7, followed by CIDR removal and PGF on Day 14; (3)
      LRTS-CIDR-PGF group-heifers with RTS 4 or less received a CIDR insert on Day 7,
      followed by CIDR removal and PGF on Day 14; and (4) HRTS-Select-Synch group
      heifers with RTS 5 received 100 MUg of gonadorelin diacetate tetrahydrate
      (gonadotropin releasing homone; im) on Day 7 and PGF on Day 14. In all groups,
      heifers observed in estrus were artificially inseminated (within 120 hours after
      PGF) using the AM-PM rule. In Experiment 1, estrus expression rates were 82.2%
      (282/343) and 88.5% (184/208) for HRTS-DPGF and LRTS-CIDR-PGF, respectively (P <
      0.05), whereas AI-PR were 51.3% (176/343) and 59.1% (123/208; P < 0.1). In
      Experiment 2, estrus expression rates were 79.6 (168/211), 86.9 (186/214) and
      84.2% (176/209) for HRTS-DPGF, HRTS-CIDR-PGF, and LRTS-CIDR-PGF groups (P > 0.1)
      and AI-PR were 52.1 (110/211), 60.3 (129/214), and 58.4% (122/209; P > 0.05). In
      Experiment 3, estrus expression rates were 77.5 (131/169), 85.5 (142/166), and
      83.3% (219/263) for HRTS-DPGF, HRTS-Select-Synch and LRTS-CIDR-PGF (P > 0.05) and
      AI-PR were 53.3 (90/169), 60.2 (100/166), and 58.6% (154/263; P > 0.1). Overall,
      estrus expression rates for HRTS-DPGF, HRTS-Select-Synch, LRTS-CIDR-PGF, and HRTS
      CIDR-PGF groups were 80.4 (581/723), 85.5 (142/166), 85.1 (579/680), and 86.9%
      (186/214), respectively; higher for heifers in LRTS-CIDR-PGF and HRTS-CIDR-PGF
      groups compared to heifers in HRTS-DPGF group (P < 0.05). The AI-PR for heifers
      in HRTS-DPGF was lower (52.0 [376/723]) compared with HRTS-Select-Synch (60.2
      [100/166]), LRTS-CIDR-PGF (58.7 [399/680]), and HRTS-CIDR-PGF (60.3 [129/214]); P
      < 0.05). In conclusion, heifers achieved greater AI-PR after CIDR-PGF or HRTS
      Select-Synch estrous synchronization protocols. Even though acceptable AI-PRs
      achieved in heifers with RTS 5 that were subjected to a double PGF protocol, the
      reproductive performance was reduced compared with other protocols used in this
      study. 

PMID- 27045629
TI  - Crosstalk between uterine serpin (SERPINA14) and pregnancy-associated
      glycoproteins at the fetal-maternal interface in pregnant dairy heifers
      experimentally infected with Neospora caninum.
AB  - Infection with Neospora caninum is the leading cause of abortion in cattle. In
      cows naturally infected with N caninum, plasma concentrations of pregnancy
      associated glycoproteins (PAG) 1 and 2 indicate fetal-placental well-being,
      whereas an excess of progesterone in the second trimester of gestation has been
      related to high abortion rate. The immunosuppressive action of progesterone on
      the uterus during gestation has been attributed in part to the uterine serpins
      (SERPINA14). This study examines expression patterns of the genes SERPINA14, PAG,
      and PAG2 at the fetal-maternal interface in dairy heifers experimentally infected
      with N caninum during the second trimester of pregnancy, when most abortions
      takes place in natural conditions. Irrespective of infection, expression of
      SERPINA14 was higher, and expression of PAG1 and PAG2 lower, for intercaruncular
      endometrium than for caruncles or cotyledons. Cotyledonary tissues showed the
      highest expression of both PAG genes but lowest expression of SERPINA14. The
      expression of SERPINA14 was significantly higher in intercaruncular endometrium
      of control dams than for infected animals, pointing to potential disruption of
      modulation of maternal immune function during infection. Dramatically reduced
      SERPINA14 was particularly apparent in infected dams with aborted fetuses. There
      was also a negative association between N caninum antibody titers with SERPINA14
      and PAG expression in infected animals, further suggesting that N caninum
      infection downregulates the uterine immunosuppressive function of SERPINA14. 

PMID- 27045631
TI  - But the Scores Don't Show How I Really Function: A Feedback Method to Reveal
      Cognitive Distortions Regarding Normal Neuropsychological Test Performance.
AB  - Neuropsychologists commonly provide feedback to patients with a high degree of
      cognitive complaints in the context of normal neuropsychological test
      performance. Patients are sometimes not reassured by this feedback because they
      blame external factors (e.g., the tests are wrong) and do not develop insight
      about internal factors (e.g., distorted self-perception) that could lead to
      better understanding about why high symptom reporting is present in the context
      of normal test results. This article presents the first formal feedback model for
      neuropsychologists to use with such patients that helps reveal the presence of
      cognitive distortions that result in high cognitive complaints. The critical
      elements of this model incorporate self-ratings of neuropsychological test
      performance, comparing those ratings to actual test performance, and presenting
      discrepancies to patients in an objective, professional, and respectful manner.
      Ways in which this feedback model may lead to improved patient outcomes and
      reductions in healthcare costs are discussed.

PMID- 27045630
TI  - Pentameric quaternary structure of the intracellular domain of serotonin type 3A
      receptors.
AB  - In spite of extensive efforts over decades an experimentally-derived structure of
      full-length eukaryotic pentameric ligand-gated ion channels (pLGICs) is still
      lacking. These pharmaceutically highly-relevant channels contain structurally
      well-conserved and characterized extracellular and transmembrane domains. The
      intracellular domain (ICD), however, has been orphaned in structural studies
      based on the consensus assumption of being largely disordered. In the present
      study, we demonstrate for the first time that the serotonin type 3A (5-HT3A) ICD
      assembles into stable pentamers in solution in the absence of the other two
      domains, thought to be the drivers for oligomerization. Additionally, the soluble
      5-HT3A-ICD construct interacted with the protein RIC-3 (resistance to inhibitors
      of cholinesterase). The interaction provides evidence that the 5-HT3A-ICD is not
      only required but also sufficient for interaction with RIC-3. Our results suggest
      the ICD constitutes an oligomerization domain. This novel role significantly adds
      to its known contributions in receptor trafficking, targeting, and functional
      fine-tuning. The innate diversity of the ICDs with sizes ranging from 50 to 280
      amino acids indicates new methodologies need to be developed to determine the
      structures of these domains. The use of soluble ICD proteins that we report in
      the present study constitutes a useful approach to address this gap. 

PMID- 27045632
TI  - Biodegradability and aquatic toxicity of quaternary ammonium-based gemini
      surfactants: Effect of the spacer on their ecological properties.
AB  - Aerobic biodegradability and aquatic toxicity of five types of quaternary
      ammonium-based gemini surfactants have been examined. The effect of the spacer
      structure and the head group polarity on the ecological properties of a series of
      dimeric dodecyl ammonium surfactants has been investigated. Standard tests for
      ready biodegradability assessment (OECD 310) were conducted for C12 alkyl chain
      gemini surfactants containing oxygen, nitrogen or a benzene ring in the spacer
      linkage and/or a hydroxyethyl group attached to the nitrogen atom of the head
      groups. According to the results obtained, the gemini surfactants examined cannot
      be considered as readily biodegradable compounds. The negligible
      biotransformation of the gemini surfactants under the standard biodegradation
      test conditions was found to be due to their toxic effects on the microbial
      population responsible for aerobic biodegradation. Aquatic toxicity of gemini
      surfactants was evaluated against Daphnia magna. The acute toxicity values to
      Daphnia magna, IC50 at 48 h exposure, ranged from 0.6 to 1 mg/L. On the basis of
      these values, the gemini surfactants tested should be classified as toxic or very
      toxic to the aquatic environment. However, the dimeric quaternary ammonium-based
      surfactants examined result to be less toxic than their corresponding monomeric
      analogs. Nevertheless the aquatic toxicity of these gemini surfactants can be
      reduced by increasing the molecule hydrophilicity by adding a heteroatom to the
      spacer or a hydroxyethyl group to the polar head groups. 

PMID- 27045633
TI  - Toxicological and biochemical responses of the earthworm Eisenia fetida exposed
      to contaminated soil: Effects of arsenic species.
AB  - Arsenic is a pollutant that can be detected in different chemical forms in soil.
      However, the toxicological effects of different arsenic species on organisms have
      received little attention. In this study, we exposed earthworms Eisenia fetida to
      artificial soils contaminated by arsenite [As(III)], arsenate [As(V)],
      monomethylarsonate (MMA) and dimethylarsinate (DMA) for 28 and 56 days. Three
      biomarkers including lipid peroxidation (LPO), metallothioneins (MTs) and
      lysosomal membrane stability (LMS) were analyzed in the organisms. In addition,
      the contents of total arsenic and arsenic species in earthworms were also
      determined to investigate the effects of bioaccumulation and biotransformation of
      arsenic on biomarkers and to evaluate the dose-response relationships. The
      results showed that the relationship between the three biomarkers and the two
      inorganic arsenic species were dose dependent, and the correlation levels between
      the biomarkers and As(III) were higher than that between the biomarkers and
      As(V). Trivalent arsenic species shows more toxicity than pentavalent arsenic on
      the earthworms at molecular and subcellular level, including oxidative damage,
      MTs induction and lysosomal membrane damage. The toxicity of MMA and DMA was
      lower than inorganic arsenic species. However, the occurrence of demethylation of
      organic arsenics could lead to the generation of highly toxic inorganic arsenics
      and induce adverse effects on organisms. The biotransformation of highly toxic
      inorganic arsenics to the less toxic organic species in the earthworms was also
      validated in this study. The biomarker responses of the earthworm to different
      arsenic species found in this study could be helpful in future environment
      monitoring programs. 

PMID- 27045634
TI  - Comparative electrochemical degradation of salicylic and aminosalicylic acids:
      Influence of functional groups on decay kinetics and mineralization.
AB  - Solutions of 100 mL with 1.20 mM of salicylic acid (SA), 4-aminosalicylic acid (4
      ASA) or 5-aminosalicylic acid (5-ASA) have been comparatively degraded by anodic
      oxidation with electrogenerated H2O2 (AO-H2O2), electro-Fenton (EF) and
      photoelectro-Fenton (PEF). Trials were carried out with a stirred tank reactor
      with a BDD anode and an air-diffusion cathode for continuous H2O2 production. A
      marked influence of the functional groups of the drugs was observed in their
      decay kinetics, increasing in the order SA < 5-ASA < 4-ASA in AO-H2O2 and 5-ASA <
      SA < 4-ASA in EF and PEF, due to the different attack of OH generated at the BDD
      surface and in the bulk from Fenton's reaction, respectively. This effect was
      clearly observed when varying the current density between 16.7 and 100 mA cm(-2).
      The relative mineralization power of the processes always followed the sequence:
      AO-H2O2 < EF < PEF. The three drugs underwent analogous mineralization abatement
      up to 88% by AO-H2O2 at 100 mA cm(-2). The mineralization rate in EF and PEF grew
      in the order: 4-ASA < 5-ASA < SA. The most powerful process was PEF, attaining
      >98% mineralization for all the drugs at 100 mA cm(-2). Oxalic and oxamic acids
      were detected as final short-linear aliphatic carboxylic acids by ion-exclusion
      HPLC, allowing the fast photolysis of their Fe(III) complexes by UVA light to
      justify the high power of PEF. 

PMID- 27045635
TI  - Transport of colloidal silica in unsaturated sand: Effect of charging properties
      of sand and silica particles.
AB  - We have studied the transport of colloidal silica in various degrees of a water
      saturated Toyoura sand column, because silica particles are widely used as
      catalyst carriers and abrasive agents, and their toxicity is reported recently.
      Since water-silica, water-sand, and air-water interfaces have pH-dependent
      negative charges, the magnitude of surface charge was controlled by changing the
      solution pH. The results show that, at high pH conditions (pH 7.4), the
      deposition of colloidal silica to the sand surface is interrupted and the silica
      concentration at the column outlet immediately reaches the input concentration in
      saturated conditions. In addition, the relative concentration of silica at the
      column outlet only slightly decreases to 0.9 with decreasing degrees of water
      saturation to 38%, because silica particles are trapped in straining regions in
      the soil pore and air-water interface. On the other hand, at pH 5 conditions (low
      pH), where sand and colloid have less charge, reduced repulsive forces result in
      colloidal silica attaching onto the sand in saturated conditions. The deposition
      amount of silica particles remarkably increases with decreasing degrees of water
      saturation to 37%, which is explained by more particles being retained in the
      sand column associated with the air-water interface. In conclusion, at higher pH,
      the mobility of silica particles is high, and the air-water interface is inactive
      for the deposition of silica. On the other hand, at low pH, the deposition amount
      increases with decreasing water saturation, and the particle transport is
      inhibited. 

PMID- 27045636
TI  - The influence of ionic strength and organic compounds on nanoparticle TiO2 (n
      TiO2) aggregation.
AB  - This study investigated the aggregation of n-TiO2 in the presence of humic acid
      (HA) and/or 17beta-estradiol (E2) under high ionic strength conditions simulating
      levels detected in landfill leachate. Aggregation of n-TiO2 was strongly
      influenced by ionic strength as well as ionic valence in that divalent cations
      (Ca(2+)) were more effective than monovalent (Na(+)) at the surface modification.
      HA or E2 enhanced aggregation of n-TiO2 in 20 mM CaCl2, however little
      aggregation was observed in 100 mM NaCl. Similarly, we observed only the
      increased aggregation of n-TiO2 in the presence of HA/E2. These results showed
      the critical role of particles' surface charges on the aggregation behaviors of n
      TiO2 that HA plays more significantly than E2. However, the slightly increased
      zeta potential and aggregation of n-TiO2 in the combination of HA and E2 at both
      20 mM CaCl2 and 100 mM NaCl means that E2 has influenced on the surface
      modification of n-TiO2 by adsorption. Based on the aggregation of n-TiO2 under
      high ionic strength with HA and/or E2, we simulated the mobility of aggregated n
      TiO2 in porous media. As a result, we observed that the mobility distance of
      aggregated n-TiO2 was dramatically influenced by the surface modification with
      both HA and/or E2 between particles and media. Furthermore, larger mobility
      distance was observed with larger aggregation of n-TiO2 particles that can be
      explained by clean bed filtration (CFT) theory. 

PMID- 27045637
TI  - Intracranial pressure and outcome in critically ill patients with aneurysmal
      subarachnoid hemorrhage: a systematic review.
AB  - BACKGROUND: Evidences supporting the use of intracranial pressure (ICP)
      monitoring after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim
      of our paper was to examine whether elevated intracranial pressure and ICP
      derived variables predict mortality and functional outcomes after aSAH. EVIDENCE
      ACQUISITION: A systematic review of the literature was performed through PubMed
      and Cochrane databases up to June 2015. Population was restricted to aSAH
      patients requiring admission to the intensive care unit. ICP was included in the
      analysis as absolute value as well as variables derived from ICP monitoring
      (pressure reactivity index, ICP pulse wave amplitude, ICP-arterial blood pressure
      wave amplitude correlation and ICP variability). Outcomes included mortality,
      neurological recovery and delayed cerebral ischemia (DCI). Quality of evidence
      was rated using the GRADE system. EVIDENCE SYNTHESIS: Twenty-six studies were
      examined. Due to heterogeneity in qualifying studies, a meta-analysis could not
      be generated. We found a correlation between elevated ICP and mortality. However,
      ICP absolute values were not independent predictors of long-term functional
      outcomes (low quality of evidence). A variable relationship between elevated ICP
      and DCI was found (very low quality of evidence). ICP-derived variables had
      higher accuracy than ICP absolute values in predicting functional outcomes
      (moderate quality of evidence). CONCLUSIONS: Elevated ICP was associated with
      higher mortality however absolute ICP values per se were not independent
      predictors of functional recovery. Variables derived from ICP monitoring are more
      accurate than ICP absolute values in predicting outcome. Given the absence of
      good quality data, additional large studies may help to better define the
      prognostic value of ICP after aSAH.

PMID- 27045638
TI  - Persistent left superior vena cava: a possible practical implication.

PMID- 27045639
TI  - The risk of infusing gelatin? Die-hard misconceptions and forgotten (or ignored)
      truths.
AB  - Fluid therapy is considered a cornerstone of perioperative and critical care
      medicine. However, the type of fluids used varies widely among different
      countries. Synthetic colloids may negatively affect coagulation and are
      potentially nephrotoxic. "Modern" hydroxyethyl starches (HES) were widely used
      until recently when their association to mortality and renal replacement therapy
      risk among critically ill patients brought to restriction by the European
      Medicines Agency in 2013. Since synthetic colloids are traditionally thought to
      be much more effective as volume expanders than crystalloids (although their
      efficacy is probably largely overrated), there is concern that physicians,
      practically deprived of HES, could be tempted to rely again on "old" gelatins.
      The aim of this contribution is to warn clinicians that gelatins share all
      potential adverse effects of other synthetic colloids, and are possibly even more
      nephrotoxic than HES. Moreover, gelatins have no beneficial effects on outcomes
      as compared with crystalloids (on the contrary, they might even increase
      mortality), and are also more expensive. Accordingly, a "return" to gelatins
      should be strongly discouraged.

PMID- 27045640
TI  - Intracranial pressure and outcome in critically ill patients with aneurysmal
      subarachnoid hemorrhage: a systematic review.
AB  - BACKGROUND: Evidences supporting the use of ICP monitoring after aneurysmal
      subarachnoid hemorrhage (aSAH) are limited. The aim of our paper is to examine
      whether elevated intracranial pressure (ICP) and ICP-derived variables predict
      mortality and functional outcomes after aSAH. METHODS: A systematic review of the
      literature was performed through PubMed and Cochrane databases up to June 2015.
      Population was restricted to aSAH patients requiring admission to the intensive
      care unit. ICP was included in the analysis as absolute value as well as
      variables derived from ICP monitoring (pressure reactivity index, ICP pulse wave
      amplitude, ICP-arterial blood pressure wave amplitude correlation and ICP
      variability). Outcomes included mortality, neurological recovery and delayed
      cerebral ischemia (DCI). Quality of evidence was rated using the GRADE system.
      RESULTS: Twenty-six studies were examined. Due to heterogeneity in qualifying
      studies, a meta-analysis could not be generated. We found a correlation between
      elevated ICP and mortality. However, ICP absolute values were not independent
      predictors of long-term functional outcomes (low quality of evidence). A variable
      relationship between elevated ICP and DCI was found (very low quality of
      evidence). ICP-derived variables had higher accuracy than ICP absolute values in
      predicting functional outcomes (moderate quality of evidence). CONCLUSIONS:
      Elevated ICP was associated with higher mortality however absolute ICP values per
      se were not independent predictors of functional recovery. Variables derived from
      ICP monitoring are more accurate than ICP absolute values in predicting outcome.
      Given the absence of good quality data, additional large studies may help to
      better define the prognostic value of ICP after aSAH.

PMID- 27045642
TI  - [Standardize the diagnosis and treatment of Cushing's disease is the only way to
      improve the level of diagnosis and treatment].

PMID- 27045641
TI  - Prepregnancy Adverse Lipid Profile and Subsequent Risk of Gestational Diabetes.
AB  - CONTEXT: Lower low-density lipoprotein (LDL) peak diameter and a predominance of
      small, dense LDL are associated with type 2 diabetes, but it is unclear whether
      they are a risk factor for gestational diabetes mellitus (GDM). OBJECTIVE: To
      evaluate whether prepregnancy lipid profile predicts the development of GDM
      during pregnancy. DESIGN: A nested case-control study among women who
      participated in a multiphasic health exam, where blood was collected and stored
      between 1984 and 1996, and who then had a subsequent pregnancy between 1984 and
      2009. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Cases were
      254 women who developed GDM. Two controls were selected for each case and matched
      for year of blood draw, age at baseline, age at pregnancy, and number of
      intervening pregnancies. MAIN OUTCOME MEASURES: Prepregnancy LDL peak diameter
      and prepregnancy lipid subfraction concentrations grouped according to size, and
      the odds of developing GDM. RESULTS: Women in the lowest quartiles of LDL peak
      diameter and high-density lipoprotein had increased odds of GDM compared with
      women in the highest quartiles (odds ratio [95% CI], 2.60 [1.37-4.94] and 1.98
      [1.01-3.86], respectively), in multivariable adjusted models. Being in the
      highest quartile of small and very small LDL subfractions also increased the odds
      of GDM (2.61 [1.35-5.03] and 2.44 [1.22-4.85], respectively). CONCLUSIONS: Lower
      LDL peak diameter size and high-density lipoprotein levels and higher levels of
      small and very small LDL subfraction groups were present years before pregnancy
      in women who developed GDM. A prepregnancy atherogenic lipid profile may help
      identify women at risk of GDM to target for prevention.

PMID- 27045643
TI  - [Use of inferior petrosal sinus sampling during the perioperative periodtreatment
      of Cushing's disease with negative magnetic resonance imaging].
AB  - OBJECTIVE: To analyze inferior petrosal sinus sampling (IPSS) in diagnosis and
      treatment of Cushing's disease with negative magnetic resonance imaging (MRI).
      METHODS: We retrospectively reviewed 79 cases of Cushing's disease with negative
      MRI in the Department of Neurosurgery of Peking Union Medical College Hospital
      from August 2012 to August 2014. Of the 79 patients, 58 underwent IPSS. There
      were 16 males and 42 females in this study, with age 12 to 65 years old. All 58
      patients underwent endocrine assessment before transsphenoidal surgery, and
      pathology specimens were examined. RESULTS: The IPSS results of all the 58
      patients suggested the excessive secretion of ACTH was from pituitary. Of the 58
      patients, visible tumor was found in 56 cases during intraoperative exploration
      (96.6%). In 29 (50%) cases, the side of pituitary where tumor was located
      predicted by IPSS was the same with intraoperative exploration. Typical tumor was
      seen in 47 cases during exploration, and the endocrine remission rate was 83.0%
      after operation. Suspicious tumor was seen in 9 cases, and endocrine response
      rate was 44.4%. No tumor was found in two cases who had no remission after
      operation. Pituitary adenoma was confirmed in 41 patients (70.7%) by pathological
      exam. And anterior or posterior lobe of pituitary was reported in 12 cases,
      pituitary hyperplasia in 5 cases. CONCLUSIONS: IPSS is recommended in Cushing's
      disease patients with negative MRI, and it is helpful to judge whether the
      excessive secretion of ACTH is from pituitary, while its value in predicting the
      lateralization of tumor is low. If IPSS results are positive, transsphenoidal
      surgery should be performed.

PMID- 27045644
TI  - [Value of desmopressin stimulation test and high dose dexamethasone suppression
      testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].
AB  - OBJECTIVE: To investigate the value of desmopressin (DDAVP) stimulation test and
      high dose dexamethasone suppression test (HDDST) in establishing the cause of
      ACTH dependent Cushing's syndrome. METHODS: The clinical data of patients with
      ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to
      September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP
      stimulation test, HDDST, and the diagnostic accordance rate when the two tests
      were combined, were evaluated based on the diagnostic gold standard. RESULTS: A
      total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH
      syndrome were included. The sensitivity and specificity of DDAVP stimulation test
      were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10,
      respectively. The standard high dose dexamethasone suppression test showed a
      higher sensitivity than overnight 8 mg dexamethasone suppression test. When the
      two tests had consistent results, the diagnostic accordance rate was 100%.
      CONCLUSIONS: DDAVP stimulation test and HDDST are both efficient modalities for
      the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of
      diagnosis can be further improved by combining the two tests.

PMID- 27045645
TI  - [Blood coagulation function change and influence factors in Cushing's syndrome
      and obesity].
AB  - OBJECTIVE: To compare and analysis blood coagulation index change and influence
      factors in Cushing's syndrome (CS) and obesity (OB) patients to provide
      theoretical evidence for improving the prognosis of them. METHODS: A total of 250
      patients with CS and 164 patients with obesity were collected from October 2012
      to August 2015 in Peking Union Medical College Hospital. Peripheral blood cells,
      liver and kidney function, blood lipid, 24 h urine free cortisol (24 hUFC) and
      blood coagulation were tested. RESULTS: The proportion of patients with abnormal
      blood coagulation indexes were 80% (200/250) and 52% (85/164) respectively in CS
      and OB patients.Compared with OB patients, coagulation and fibrinolysis values
      decreased significantly in CS patients. In addition, the shortening of activated
      partial thromboplastin time (APTT) was more obvious in CS patients, while 24
      hUFC, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C) were higher than OB. In OB patients, body
      mass index (BMI), fasting blood-glucose (FBG), TC and LDL-C were associated with
      blood coagulation abnormalities; in patients with CS, alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), 24 hUFC, white blood cell (WBC) and
      platelet (PLT) were associated with blood coagulation abnormalities. CONCLUSION:
      Higher coagulation state in CS is likely relevant to higher level of TC, LDL and
      cortisol hydrocortisone which, in return, have impact on the blood coagulation
      system, therefore, the risk of thrombosis in CS patients is increased.

PMID- 27045646
TI  - [Clinical features of myasthenia gravis with thyroid disease with 106 patients].
AB  - OBJECTIVE: To report the presentation, clinical course and prognosis of
      myasthenia gravis (MG) with thyroid disease. METHODS: Retrospective data analysis
      was conducted.Between 2004 and 2013, we reviewed a total of 106 patients with MG.
      We analyzed the clinical features, the relationship between the thyroid function,
      antibodies and the clinical course, prognosis. RESULTS: (1) In our study, 20/106
      (18.87%) patients were thyroid function-abnormal, 37/106 (34.91) were
      thyroglobulin antibodies (TGAb) and/or thyroid microsomal antibody (TMAb)
      positive, and abnormality was observed in 46 (43.40%) of the thyroid gland.
      Thyroid antibody positive rate was higher than abnormal thyroid function rate,
      and the difference was significant (P=0.036). (2) The thyroid stimulating hormone
      (TSH) level ((2.9+/-4.0) mIU/L) of ocular MG was higher than the level ((1.5+/
      1.1) mIU/L) of generalized MG (P=0.01). (3) The transformation time of 52 ocular
      type to generalized type was longer in higher antibody group than in normal group
      (P=0.04). And there were no significant differences between the elevated TSH type
      and the normal TSH type, the abnormal thyroid function type and normal thyroid
      function type, the abnormal thyroid type and the normal thyroid type. (4)
      Comparing the TSH level, total antibody level, TGAb, and TMAb level between the
      ease group and the unease group in the course of 1 year, 2 years, 5 years, there
      were no significant differences (all P>0.05). CONCLUSIONS: MG is often companied
      with thyroid abnormalities. MG patients are more susceptible to hashimoto
      thyroiditis and other autoimmune thyroid diseases. Ocular type patients are more
      likely to suffer from thyroid function decrease than the generalized type. MG
      patients with hashimoto thyroiditis and other autoimmune thyroid diseases are
      more sensitive to respond to therapy means like glucocorticoid therapy, and the
      short-term prognosis is relatively good. There are no significant correlations
      between the MG remission rate and TSH level, total antibody level, TGAb and TMAb
      level.

PMID- 27045647
TI  - [Clinical and electrophysiological characteristics and therapeutic analysis of 9
      patients with Lewis-Sumner syndrome].
AB  - OBJECTIVE: To investigate the clinical characteristics, electrophysiological
      findings and treatment response of Lewis-Sumner syndrome (LSS). METHODS: Data of
      nine patients with LSS, who were diagnosed and treated from May 2008 to August
      2014 in Department of Neurology, Peking University Third Hospital, were analyzed
      retrospectively, including clinical features, electrophysiological studies,
      pathological characteristics, therapy and follow up. RESULTS: The nine cases
      included seven males and two females, with the average age being 29 years old (18
      64 years old). The follow-ups after treatment were between 6 months to 48 months.
      All 9 cases were asymmetrical onset, and the distal part of limbs was initially
      affected in 8 cases. Five cases presented with the initial symptom of
      sensorimotor, 3 cases with purely motor and only 1 case with sensory. The disease
      developed two forms: multifocal distribution and symmetrical distribution.
      Electrophysiological studies demonstrated conduction blocks on non-entrapment
      sites, involving mainly median nerve and ulnar nerve. Sural nerve biopsy
      presented mild demyelination without inflammatory infiltration. The symptoms of
      patients had some degrees of improvement after immunotherapy, and the prognosis
      was favorable. CONCLUSIONS: Lewis-Sumner syndrome presents the initial symptoms
      of asymmetrical sensorimotor neuropathy mostly affecting the upper extremities.
      Median nerve and ulnar nerve are the most common involvements.
      Electrophysiological studies demonstrate motor nerve conduction block. The major
      finding of pathology is mild demyelinated. The patients have a positive response
      to immunotherapy.

PMID- 27045648
TI  - [Understanding the reasons behind the low utilization of thrombolysis in
      hyperacute ischemic stroke].
AB  - OBJECTIVE: The study aimed to analyze the influencing factors of thrombolysis
      therapy in acute ischemic stroke patients with onset time less than 4.5 hours.
      METHODS: We consecutively prospectively screened acute ischemic stroke patients
      with onset time less than 4.5 hours from emergency department, outpatients and
      inpatients of neurology department, and image center in our hospital over a 31
      month time period (April 2012-November 2014). The rate of thrombolysis and the
      reasons for not receiving thrombolysis were analyzed. RESULTS: A total of 538
      patients who met the inclusion criteria were included (68.2% males, mean age 67+/
      13 years old). Only 104 (19.3%) patients received thrombolysis. The main reasons
      for the patients not receiving thrombolysis included minor symptoms (172 cases,
      39.6%), rapidly improving symptoms and high possibility of transient ischemic
      attack (TIA) (59 cases, 13.6%), patients or families refusing thrombolysis (44,
      10.1%), in-hospital delay (38, 8.8%), elderly people with age over than 80 years
      old (38, 8.8%). CONCLUSIONS: The thrombolysis rate within time window of acute
      ischemic stroke is remarkably higher than that of several years ago in China. The
      main reasons for not receiving thrombolysis are minor and rapidly improving
      symptoms, patients or families' refusal, in-hospital delay, elderly people with
      age over than 80 years old.

PMID- 27045649
TI  - [Regional homogeneity changes in patients with obstructive sleep apnea-hypopnea
      syndrome: resting-state functional MRI study].
AB  - OBJECTIVE: To investigate the change of regional homogeneity (ReHo) in patients
      with obstructive sleep apnea-hypopnea syndrome (OSAHS) using resting-state
      functional magnetic resonance imaging(fMRI). METHODS: Resting-state fMRI data
      were collected from 15 patients with OSAHS and 15 normal controls. Patients were
      enrolled from the Sleep Laboratory of the Otolaryngology-Head and Neck Surgery
      Department of Zhongda Hospital, Southeast University, Nanjing from November 2014
      to June 2015. The data were analyzed with the ReHo method and compared between
      OSAHS and controls. RESULTS: The ReHo showed a significant increase in the
      posterior lobe of right cerebellum (t=4.292 1, P<0.01), posterior lobe of left
      cerebellum (t=4.350 6, P<0.01), right brainstem (t=5.276 6, P<0.01), right
      occipital lobe (t=3.620 9, P= 0.001), left basal ganglia (t=3.385 6, P=0.002) and
      left temporal lobe (t=4.781 2, P<0.01) and a decrease in the right middle frontal
      gyrus (t=-3.564 4, P= 0.001), right inferior parietal lobe (t=-4.123 7, P<0.01)
      and bilateral superior frontal gyrus (t=-3.500 9, P=0.002) in patients with
      OSAHS. Furthermore, the average ReHo values of the posterior lobe of bilateral
      cerebellum was positively correlated with the MMSE scores (r=0.682, P=0.012), the
      LMT scores (r=0.623, P=0.013) and the LMT-delayed recall scores (r=0.577,
      P=0.024), while negatively correlated with the TMT-A scores (r=-0.723, P=0.002);
      the average ReHo values of the right middle frontal gyrus (r=0.661, P=0.007) was
      positively correlated with the TMT-A scores. CONCLUSION: The current findings
      indicate that significant changes of ReHo in the global brain regions have been
      detected in OSAHS patients and the compensatory change of brain function occur.
      Abnormal ReHo values in the posterior lobe of bilateral cerebellum and right
      middle frontal gyrus could serve as potential biomarkers for assessment of
      neuronal damage and further provides insights into the biological mechanism of
      the disease.

PMID- 27045650
TI  - [Clinical outcomes of single-level minimally invasive transforaminal lumbar
      interbody fusion with tube work channel system].
AB  - OBJECTIVE: To evaluate the clinical effectiveness of minimally invasive
      transforaminal lumbar interbody fusion (MIS-TLIF) in single-level lumbar
      degeneration disease treatment. METHODS: We retrospectively analyzed the clinical
      data of 32 patients who underwent the MIS-TLIF surgery from Nov. 2013 to Oct.
      2014 in Shanghai Tongji Hospital.Clinical and radiological outcomes including
      operation time, X-ray exposure, surgical blood loss, drainage blood loss,
      complications, visual analogue scores (VAS), Oswestry disability index (ODI)
      scores, average intervertebral space and fusion rate. VAS scores of low back and
      leg pain, ODI scores were recorded before and after surgery to evaluate the
      functional recovery, average intervertebral space height, lumbar and surgical
      Cobb angle were measured by X-rays before and after surgery to assess recovery of
      intervertebral space height and the change of lumbar kyphosis. The Bridwell
      criterion was used for evaluating the interbody fusion and the MacNab criterion
      was used for assessment after surgery. RESULTS: All the patients received
      successful surgery. The mean operative time was (171.9+/-31.1) min with (36.7+/
      16.4) seconds radiation exposure, and mean blood loss was (153.3+/-64.8) ml,
      drainage blood loss was (58.9+/-49.2) ml. All cases were followed up for (11.6+/
      3.3) months. Compared with preoperation, VAS score of low back and leg pain, ODI
      score and average intervertebral space showed significant improvements after
      surgery. There were 26 (81.3%) cases were grade I and II 3 months after surgery
      according to the Bridwell criteria while the number was 31 (96.9%) at the last
      follow-up. The clinical results were excellent in 22 cases, good in 8 cases and
      fair in 2 cases according to the MacNab criteria at the final follow-up.
      CONCLUSION: MIS-TLIF under Spotlight work channel system is a safe and effective
      procedure for single segment lumbar degenerative disease and it may offer
      patients additional advantages in less trauma and reduction of hospital stay.

PMID- 27045651
TI  - [Correlation between shifting of gravity center position and functional recovery
      after total hip arthroplasty in patients who suffered from avascular necrosis of
      the femoral head].
AB  - OBJECTIVE: To explore correlation between shifting of gravity center position
      (GCP) and functional recovery after total hip arthroplasty (THA) in patients who
      suffered from avascular necrosis of the femoral head. METHODS: Eighty six
      patients (49 right hip, 37 left hip) with avascular necrosis of the single
      femoral head who underwent THA at our department from January 2011 to December
      2013 were investigated. Each patient was evaluated with Harris score system and
      measured GCP by corresponding instrument preoperatively and six month, one-year
      postoperatively. Pearson's correlation analysis was used to analyze the
      correlation between shifting degree of GCP and changing degree of Harris score at
      the above time points. RESULTS: Harris score significantly improved after surgery
      (P<0.01), and there was a direct linear relationship between shifting degree of
      GCP and changing degree of Harris score at the same period after the surgery, and
      the adjusted R(2) value between them were 0.521 at six month and 0.46 at one year
      after operation. CONCLUSIONS: As the function of the hip recovers, the GCP moves
      from its initial position to the operative side after THA. The shifting degree of
      GCP can be a reflection of recovery of the joint function in some extent.

PMID- 27045652
TI  - [Clinical and laboratory features of psoriatic arthritis which antedates
      psoriasis].
AB  - OBJECTIVE: To analyze the clinical and laboratory features of psoriatic arthritis
      (PsA) which antedates psoriasis. METHODS: The clinical and laboratory data
      including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      immunoglobulins, antibodies of 113 patients with PsA were analyzed
      retrospectively and compared by order of the occurrence of arthritis. RESULTS:
      The occurrence of psoriatic arthritis which antedates psoriasis was 22.1% in the
      study. The onset of arthritis was 2 months to 25 years earlier than psoriasis.
      Arthritis of distal interphalangeal (DIP) joints was frequently involved in this
      group and arthritis of hip joints was rare. Positive HLA-B27 and higher level of
      platelet (PLT), ESR, CRP, and IgA were common in patients with psoriatic
      arthritis which antedates psoriasis. CONCLUSION: Arthritis of DIP joints and
      elevated inflammatory markers are frequently involved in patients with psoriatic
      arthritis which antedates psoriasis, and somewhat they are associated with
      disease activity.

PMID- 27045653
TI  - [Mechanism of neuroprotective effects of fibroblast growth factor 2 in the mouse
      model of ALS].
AB  - OBJECTIVE: To examine the neuroprotective effects of FGF-2 and explore the
      underlying mechanisms involved in its effects on neural precursor cells (NPCs)
      and S-IR boutons. METHODS: The mice models were established, and the animals were
      randomly divided into 3 groups: non-transgenic wild type group (WT), superoxide
      dismutase (SOD)1 G93A G1H transgenic group (SOD1), and fibroblast growth factor
      (FGF)-2-treated group (FGF-2), each group 40 mice. Mice of FGF-2 group were
      treated with FGF-2 at postnatal day 60 (P60). These three groups were examined at
      postnatal day 90 (P90) and 120 (P120). The changes of NPCs and S-IR boutons were
      checked by means of immunohistochemical detection. RESULTS: When mice were
      examined at P90 and P120, the number of Nestin(+) NPCs was (47+/-24) and (147+/
      45) in the SOD1 group, (77+/-27) and (285+/-103) in the FGF-2 group. A marked
      increase was detected in the FGF-2 mice compared to the SOD1 mice at P120
      (P<0.01). At P120 there was a clear decrease in the density of S-IR boutons in
      the SOD1 (0.5+/-0.1) and FGF-2 (0.8+/-0.1) mice compared to the WT (0.9+/-0.1)
      mice, but a more significant decrease in the density of S-IR boutons was detected
      in the SOD1 mice compared to the FGF-2 mice (P<0.05). CONCLUSION: FGF-2 may be a
      useful treatment to provide neuroprotection against neurodegeneration in
      amyotrophic lateral sclerosis (ALS) by encouraging the proliferation of NPCs and
      delaying the decrease in the density of S-IR boutons.

PMID- 27045654
TI  - [Nuclear translocation of beta-catenin represses membrane localization of NIS in
      human thyroid cancer cells].
AB  - OBJECTIVE: To explore whether nuclear translocation of beta-catenin affects
      functional expression of sodium iodide symporter (NIS) in human thyroid cancer
      cells. METHODS: Two kinds of beta-catenin nuclear translocation cell models were
      firstly established with transfection of hypoxia inducible factor 1alpha (HIF
      1alpha) and beta-catenin cDNA in human thyroid cancer cell line FTC133. Then the
      expression of beta-catenin were further interfered by shRNA in above two cell
      models. After that, the influence of beta-catenin nuclear localization on the
      functional expression of NIS, iodine uptake potency, epithelial-mesenchymal
      transition (EMT) characteristics, tumor growth curve and treatment effect
      inducing by radioactive iodine were comparatively analyzed in vitro and in vivo
      trials. Additionally, the underlying mechanism of NIS functional expression was
      also assessed via identifying the activation of beta-catenin signal pathway.
      RESULTS: In vitro assay showed prominent EMT phenotype in the above two beta
      catenin nuclear translocation cell models, and in vitro proliferation and
      invasion potential of cancer cells markedly increased (all P<0.05); NIS protein
      expression translocated from cell membrane to cytoplasma. Cell iodide uptake in
      vitro decreased about 50.0% and 37.5%, respectively in above two beta-catenin
      translocation cell models (both P<0.05). Moreover, beta-catenin nuclear
      translocation was correlated with phosphorylation expressions of beta-catenin
      Ser45, Y654 and GSK-3beta Ser9. Most importantly, all above changes associated
      with beta-catenin nuclear translocation could be effectively reversed after
      blockade of beta-catenin expression. In the animal model, tumor growth potential
      and tumor mass were significantly inhibited by both blockade of beta-catenin and
      radioactive iodide ((131)I) (all P<0.05). Meanwhile, immunohistochemistry
      demonstrated that beta-catenin nuclear translocation remained in subcutaneous
      tumor cells after transplantation, and showed negatively associated with NIS
      membrane expression. CONCLUSION: beta-catenin nuclear translocation is a vital
      regulatory pathway involved in functional expression of NIS in human thyroid
      cancer cells.

PMID- 27045655
TI  - [Effects of lipopolysaccharide and dexamethasone on the expression of
      Kisspeptin/GPR54 in mouse hypothalamus].
AB  - OBJECTIVE: To evaluate the effects of lipopolysaccharide (LPS) and dexamethasone
      on function of hypothalamus-pituitary-testis axis and to explore the possible
      underlying mechanisms. METHODS: LPS (100 MUg/kg), dexamethasone (DEX, 1 mg/kg)
      and phosphate buffer saline (PBS) were injected subcutaneously into castrated
      mice (n=5 in each group) for 4 weeks. The expression of Kisspeptin and its
      receptor GPR54 in hypothalamus were measured by immunohistochemistry, and plasma
      luteinizing hormone (LH) were measured by chemiluminescence immunoassay. RESULTS:
      After LPS and DEX were administered for 4 weeks, the LH level in LPS group and
      DEX group was (1.79+/-0.74) U/L and (2.19+/-0.60) U/L, respectively, which were
      lower than PBS group (4.87+/-1.25) U/L (all P<0.01). In LPS group, after
      treatment, the kisspeptin immunohistochemistry index in hypothalamus was 4.2+/
      1.1, which was lower than the control group (10.2+/-1.6, P<0.05). The GPR54
      immunohistochemistry index in hypothalamus was 3.6+/-0.5, which was lower than
      PBS group (6.2+/-1.8, P<0.05). In DEX group, the expressions of kisspeptin and
      GPR 54 in hypothalamus did not change after treatment. CONCLUSIONS: LPS may
      downregulate function of hypothalamus-pituitary-testis axis through
      Kisspeptin/GPR54 system. Dexamethasone could suppress function of gonadal axis as
      well, while the underlying mechanism is still unclear.

PMID- 27045656
TI  - Assessment of drug metabolism enzyme and transporter pharmacogenetics in drug
      discovery and early development: perspectives of the I-PWG.
AB  - Genetic variants of drug metabolism enzymes and transporters can result in high
      pharmacokinetic and pharmacodynamic variability, unwanted characteristics of
      efficacious and safe drugs. Ideally, the contributions of these enzymes and
      transporters to drug disposition can be predicted from in vitro experiments and
      in silico modeling in discovery or early development, and then be utilized during
      clinical development. Recently, regulatory agencies have provided guidance on the
      preclinical investigation of pharmacogenetics, for application to clinical drug
      development. This white paper summarizes the results of an industry survey
      conducted by the Industry Pharmacogenomics Working Group on current practice and
      challenges with using in vitro systems and in silico models to understand
      pharmacogenetic causes of variability in drug disposition. 

PMID- 27045657
TI  - Introduction: beyond toxins removal, towards high-quality dialysis.
AB  - The choice of dialyzer may affect the dialysis process more than any other single
      component of the dialysis system. Over the past five decades, membranes used for
      the treatment of chronic kidney disease have continuously evolved, and the use of
      classical non-modified cellulose membranes has declined in favor of cellulose
      based membranes in which the basic structure has been modified to improve the
      biocompatibility profile of the material as well as membranes based on synthetic
      polymers. Dialysis membranes with the best biological properties should be
      biocompatible, exclude impurities in the dialysate and have a large pore size. A
      high adsorptive capacity, a main feature of the polymethylmetacrylate (PMMA)
      membranes, is high helpful and may both increase the total amount of solutes
      removed and removes different kinds of solutes. Moreover, PMMA dialyzer membrane
      has a good chance to obtain an optimal rather than an adequate dialysis in the
      field of biocompatibility, immune regulation and inflammation.

PMID- 27045658
TI  - Tissue-specific Differentiation Potency of Mesenchymal Stromal Cells from
      Perinatal Tissues.
AB  - Human perinatal tissue is an abundant source of mesenchymal stromal cells(MSCs)
      and lacks the ethical concerns. Perinatal MSCs can be obtained from various
      tissues as like amnion, chorion, and umbilical cord. Still, little is known of
      the distinct nature of each MSC type. In this study, we successfully isolated and
      cultured MSCs from amnion(AMSCs), chorion(CMSCs), and umbilical cord(UC-MSCs).
      Proliferation potential was different among them, that AMSCs revealed the lowest
      proliferation rate due to increased Annexin V and senescence-associated beta
      galactosidase positive cells. We demonstrated distinct characteristic gene
      expression according to the source of the original tissue using microarray. In
      particular, genes associated with apoptosis and senescence including CDKN2A were
      up-regulated in AMSCs. In CMSCs, genes associated with heart morphogenesis and
      blood circulation including HTR2B were up-regulated. Genes associated with
      neurological system processes including NPY were up-regulated in UC-MSCs.
      Quantitative RT-PCR confirmed the gene expression data. And in vitro
      differentiation of MSCs demonstrated that CMSCs and UC-MSCs had a more pronounced
      ability to differentiate into cardiomyocyte and neural cells, respectively. This
      study firstly demonstrated the innate tissue-specific differentiation potency of
      perinatal MSCs which can be helpful in choosing more adequate cell sources for
      better outcome in a specific disease. 

PMID- 27045660
TI  - Correction: microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched
      Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular
      Degeneration.

PMID- 27045661
TI  - Intentional burns - A form of gender based violence in Nepal.

PMID- 27045662
TI  - Trigonal Pyramidal {AsO2(OH)} Bridging Tetranuclear Rare-Earth Encapsulated
      Polyoxotungstate Aggregates.
AB  - The one-pot assembly reaction of Na2WO4.2H2O, RE(NO3)3.6H2O, and NaAsO2 in the
      participation of dimethylamine hydrochloride as an organic solubilizing agent in
      the acidic aqueous solution led to a class of trigonal pyramidal {AsO2(OH)}
      bridging rare-earth substituted arsenotungstate (AT) aggregates
      [H2N(CH3)2]8Na8{[W3RE2(H2O)8AsO8(OH)][B-alpha-AsW9O33]2}2.65H2O [RE = Eu(III)
      (1), Gd(III) (2), Tb(III) (3), Dy(III) (4), Ho(III) (5), Y(III) (6)], which were
      structurally characterized by elemental analyses, IR spectra, single-crystal X
      ray diffraction, and thermogravimetric (TG) analyses. The common structural
      feature of 1-6 is that their polyoxoanions consist of a novel tetrameric unit
      [(W3RE2(H2O)8AsO8(OH))(B-alpha-AsW9O33)2]2(16-) constituted by four trivacant
      Keggin [alpha-AsW9O33](9-) fragments linked through an unseen elliptical
      [W6RE4(H2O)16As2O16(OH)2](20+) moiety. Their polyoxoanionic infrastructures can
      also be described as a fusion of two equivalent dimeric subunits
      [(W3RE2(H2O)8O7)(B-alpha-AsW9O33)2](8-) bridged via two MU2-{AsO2(OH)} linkers.
      To the best of our knowledge, such a linking mode with trigonal pyramidal
      {AsO2(OH)} groups as linkers connecting adjacent RE containing polyoxometalate
      moieties together is very rare. The thermal stability of 1-6 was also
      investigated on the crystalline samples, and the thermal decomposition processes
      of 1, 4, and 6 were comparatively deeply studied. The fluorescent properties and
      decay times of 1, 3, and 4 were measured, and they exhibit the characteristic
      emissions of RE centers. The lifetimes of 1 and 3 mainly originate from the
      contribution of RE ions whereas the overall lifetime of 4 is contributed by the
      synergistic interactions of AT fragments and Dy(3+) ions. 

PMID- 27045663
TI  - Comparing biomarker measurements to a normal range: when to use standard error of
      the mean (SEM) or standard deviation (SD) confidence intervals tests.
AB  - This commentary is the second of a series outlining one specific concept in
      interpreting biomarkers data. In the first, an observational method was presented
      for assessing the distribution of measurements before making parametric
      calculations. Here, the discussion revolves around the next step, the choice of
      using standard error of the mean or the calculated standard deviation to compare
      or predict measurement results. 

PMID- 27045664
TI  - NanoLuc: A Small Luciferase Is Brightening Up the Field of Bioluminescence.
AB  - The biomedical field has greatly benefited from the discovery of bioluminescent
      proteins. Currently, scientists employ bioluminescent systems for numerous
      biomedical applications, ranging from highly sensitive cellular assays to
      bioluminescence-based molecular imaging. Traditionally, these systems are based
      on Firefly and Renilla luciferases; however, the applicability of these enzymes
      is limited by their size, stability, and luminescence efficiency. NanoLuc (NLuc),
      a novel bioluminescence platform, offers several advantages over established
      systems, including enhanced stability, smaller size, and >150-fold increase in
      luminescence. In addition, the substrate for NLuc displays enhanced stability and
      lower background activity, opening up new possibilities in the field of
      bioluminescence imaging. The NLuc system is incredibly versatile and may be
      utilized for a wide array of applications. The increased sensitivity, high
      stability, and small size of the NLuc system have the potential to drastically
      change the field of reporter assays in the future. However, as with all such
      technology, NLuc has limitations (including a nonideal emission for in vivo
      applications and its unique substrate) which may cause it to find restricted use
      in certain areas of molecular biology. As this unique technology continues to
      broaden, NLuc may have a significant impact in both preclinical and clinical
      fields, with potential roles in disease detection, molecular imaging, and
      therapeutic monitoring. This review will present the NLuc technology to the
      scientific community in a nonbiased manner, allowing the audience to adopt their
      own views of this novel system.

PMID- 27045665
TI  - Motion compensated controller for a tendon-sheath-driven flexible endoscopic
      robot.
AB  - BACKGROUND: A tendon-sheath system (TSS) has the advantages of being relatively
      compact in size, flexible and low cost, and therefore is favoured in building
      flexible endoscopic robots to pass through long and tortuous human lumen. TSS,
      however, is prone to nonlinear behaviors such as backlash, hysteresis and
      direction dependent properties. A compensation technique is required to improve
      its positioning performance. METHODS: Tension and elongation models of TSS are
      analyzed. A feedforward motion compensation controller is designed to compensate
      the asymmetric backlash behavior of the TSS in real time. RESULTS: Motion
      tracking experiments were conducted on a TSS driven two DOFs continuum
      manipulator. The results showed that using the proposed compensation methods,
      tracking error can be reduced by 74%. CONCLUSIONS: The proposed compensation
      method is useful for controlling flexible continuum robots, which are anticipated
      to have emerging roles in assisting surgeons to perform the increasingly
      technically challenging endoscopic procedures. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27045666
TI  - In vitro bioaccessibility of proteins and lipids of pH-shift processed
      Nannochloropsis oculata microalga.
AB  - The pH-shift process fractionates biomass into soluble proteins and insoluble
      fractions, followed by precipitation and recovery of the solubilized proteins.
      Nannochloropsis oculata in seawater was subjected to the pH-shift process,
      followed by digestion of various intermediates and product fractions of the
      process, using the Infogest in vitro digestion model (Minekus et al., 2014) with
      added gastric lipase. As measures for protein and lipid accessibility, degrees of
      protein hydrolysis and fatty acid liberation were assessed post-digestion and
      compared to the amounts of peptide bonds and total fatty acids present in the raw
      materials. Results showed that neither proteins nor lipids of intact
      Nannochloropsis cells were accessible to the mammalian digestive enzymes used in
      the digestion model. Cell disruption, and to a lesser extent, further pH-shift
      processing with protein solubilisation at pH 7 or pH 10, increased the
      accessibility of lipids. For proteins, differences amongst the pH-shift processed
      materials were non-significant, though pre-freezing the product prior to
      digestion increased the accessibility from 32% to 47%. For fatty acids, pH-shift
      process-products gave rise to 43% to 52% lipolysis, with higher lipolysis for
      products solubilised at pH 10 as opposed to pH 7. Our results indicate the
      importance of processing to produce an algal product that has beneficial
      nutritional properties when applied as food or feed. 

PMID- 27045667
TI  - Changing Patterns of Disease and Mortality at the Children's Hospital, Accra: Are
      Infections Rising?
AB  - BACKGROUND: The Millennium Development Goals (MDGs) have led to reductions in
      child mortality world-wide. This has, invariably, led to the changes in the
      epidemiology of diseases associated with child mortality. Although facility based
      data do not capture all deaths, they provide an opportunity to confirm diagnoses
      and insight into these changes which are relevant for further disease control.
      OBJECTIVE: To identify changes in the disease pattern of children who died at the
      Princess Marie Louise Children's Hospital (PML) in Ghana from 2003-2013. METHODS:
      A cross sectional review of mortality data was carried out at PML. The age, sex,
      duration of admission and diagnosis of consecutive patients who died at the
      hospital between 2003 and 2013 were reviewed. This information was entered into
      an Access database and analysed using Stata 11.0 software. RESULTS: Altogether,
      1314 deaths (3.6%) occurred out of a total of 37,012 admissions. The majority of
      the deaths, 1187 (90.3%), occurred in children under the age of 5 years. While
      deaths caused by malaria, malnutrition, HIV infection and diarrhoea decreased,
      deaths caused by pneumonia were rising. Suspected septicaemia and meningitis
      showed a fluctuating trend with only a modest decrease between 2012 and 2013. The
      ten leading causes of mortality among under-fives were malnutrition, 363 (30.6%);
      septicaemia, 301 (25.4%); pneumonia, 218 (18.4%); HIV infection, 183 (15.4%);
      malaria, 155 (13.1%); anaemia, 135 (11.4%); gastroenteritis/dehydration, 110
      (9.3%); meningitis, 58 (4.9%); tuberculosis, 34 (2.9%) and hypoglycaemia, 27
      (2.3%). For children aged 5-9 years, the leading causes of mortality were
      malaria, 42 (42.9%); HIV infection, 27 (27.6%); anaemia, 14 (14.3%); septicaemia,
      12 (12.2%); meningitis, 10 (10.2%); malnutrition, 9 (9.2%); tuberculosis, 5
      (5.1%); pneumonia, 4 (4.1%); encephalopathy, 3 (3.1%); typhoid fever, 3 (3.1%)
      and lymphoma, 3 (3.1%). In the adolescent age group, malaria, 8 (27.6%); anaemia,
      6 (20.7%); HIV infection, 5 (17.2%); sickle cell disease, 3 (10.3%) and
      meningitis, 3 (10.3%) were most common. CONCLUSION: There has been a decline in
      the under-five mortality at PML over the years; however, deaths caused by
      pneumonia appear to be rising. This highlights the need for better diagnostic
      services, wider HIV screening and clinical audits to improve outcomes in order to
      achieve further reductions in child mortality and maintain the gains.

PMID- 27045668
TI  - Clinical drug-drug interactions of bosentan, a potent endothelial receptor
      antagonist, with various drugs: Physiological role of enzymes and transporters.
AB  - Bosentan, an endothelin-1 (ET) receptor antagonist is an important drug for the
      effective management of patients with pulmonary arterial hypertension. Bosentan
      has a rather complicated pharmacokinetics in humans involving multiple
      physiological components that have a profound influence on its drug disposition.
      Bosentan is mainly metabolized by cytochrome P450 (CYP) 3A4 and 2C9 enzymes with
      the involvement of multiple transporters that control its hepatic uptake and
      biliary excretion. The involvement of phase 2 metabolism of bosentan is a key to
      have an enhanced biliary excretion of the drug-related products. While bosentan
      exhibits high protein binding restricting the drug from extensive distribution
      and significant urinary excretion, bosentan induces its own metabolism by an
      increased expression of CYP3A4 on repeated dosing. Due to the above properties,
      bosentan has the potential to display drug-drug interaction with the co
      administered drugs, either being a perpetrator or a victim. The intent of this
      review is manifold: a) to summarize the physiological role of CYP enzymes and
      hepatic-biliary transporters; b) to discuss the mechanism(s) involved in the
      purported liver injury caused by bosentan; c) to tabulate the numerous clinical
      drug-drug interaction studies involving the physiological interplay with CYP
      and/or transporters; d) to provide some perspectives on dosing strategy of
      bosentan. 

PMID- 27045669
TI  - Effects of Cd2+ on the epithelial Na+ channel (ENaC) investigated by experimental
      and modeling studies.
AB  - The function of the epithelial Na+ channel from the apical membrane of many Na+
      transporting epithelia is modulated by various chemical compounds from the
      extracellular space, such as heavy metals, protons or chloride ions. We have
      studied the effect of extracellular Cd2+ on the function of the epithelial Na+
      channel (ENaC) in heterologously expressed Xenopus laevis oocytes and Na+
      transporting epithelia. We assayed channel function as the amiloride-sensitive
      sodium current (I(Na)). Cd2+ rapidly and voltage-independently inhibited INa in
      oocytes expressing alphabetagamma Xenopus ENaC (xENaC). The extracellular Cd2+
      inhibited Na+ transport and showed no influence on ENaC trafficking, as revealed
      by concomitant measurements of the transepithelial current, conductance and
      capacitance in Na+-transporting epithelia. Instead, amiloride inhibition was
      noticeably diminished in the presence of Cd2+ on the apical membrane. Using
      molecular modeling approaches, we describe the amiloride binding sites in rat and
      xENaC structures, and we present four putative binding sites for Cd2+. These
      results indicate that ENaC functions as a sensor for external Cd2+.

PMID- 27045670
TI  - Gender and chronological age affect erythrocyte membrane oxidative indices in
      citrate phosphate dextrose adenine-formula 1 (CPDA-1) blood bank storage
      condition.
AB  - It is well known that in vitro storage lesions lead to membrane dysfunction and
      decreased number of functional erythrocytes. As erythrocytes get older, in
      storage media as well as in peripheral circulation, they undergo a variety of
      biochemical changes. In our study, the erythrocytes with different age groups in
      citrate phosphate dextrose adenine-formula 1 (CPDA-1) storage solution were used
      in order to investigate the possible effect of gender factor on oxidative damage.
      Oxidative damage biomarkers in erythrocyte membranes such as ferric reducing
      antioxidant power, pro-oxidant-antioxidant balance, protein-bound advance
      glycation end products, and sialic acid were analyzed. Current study reveals that
      change in membrane redox status during blood-bank storage condition also depends
      on both gender depended homeostatic factors and the presence of CPDA-1. During
      the storage period in CPDA-1, erythrocytes from the male donors are mostly
      affected by free radical-mediated oxidative stress but erythrocytes obtained from
      females are severely affected by glyoxidative stress. 

PMID- 27045671
TI  - Fructus sophorae attenuates secretion of proinflammatory mediators and cytokines
      through the modulation of NF-kappaB and MAPK signaling pathways in LPS-stimulated
      RAW 264.7 macrophages.
AB  - This study investigated the inhibitory effects and underlying mechanisms of
      fructus sophorae, the dried ripe fruit of Styphnolobium japonicum (L.) Schott, on
      the production of proinflammatory molecules in lipopolysaccharide (LPS)
      stimulated RAW 264.7 macrophages. The results indicated that pretreatment with
      noncytotoxic concentrations of fructus sophorae extract (FSE) significantly
      inhibited the release of the proinflammatory mediators nitric oxide (NO) and
      prostaglandin E(2), which were associated with the downregulation of both mRNA
      and protein for inducible NO synthase and cyclooxygenase-2, respectively, in LPS
      challenged RAW 264.7 cells. FSE also blocked the LPS-induced expression of the
      proinflammatory cytokines interleukin (IL)-6 and IL-1beta. Furthermore, the
      results showed that FSE efficiently attenuated the LPS-induced nuclear
      translocation of nuclear factor-kappa B (NF-kappaB) and phosphorylation of the
      mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase
      (ERK) and c-Jun N-terminal kinase (JNK) but not p38 MAPK. These results suggest
      that FSE exhibits anti-inflammatory activity by inhibiting proinflammatory
      mediators and cytokines through the inactivation of NF-kappaB, ERK and JNK, and
      it may offer therapeutic potential for treating inflammatory diseases accompanied
      with macrophage activation.

PMID- 27045672
TI  - The tolerability of dextran-coated iron oxide nanoparticles during in vivo
      observation of the rats.
AB  - Superparamagnetic iron oxide nanoparticles (SPION) have attracted a lot of
      interest due to their widespread biomedical and diagnostic applications. Coating
      the SPIONs with various surface layers can provide an interface between the core
      and the surrounding environment. The aim of this study was to examine the in vivo
      behaviour of dextran-coated iron oxide nanoparticles (D-IONPs) in aqueous
      suspensions. The SPIONs stabilized with dextran (D-IONPs) were synthesized in
      aqueous solutions by co-precipitation method. The average grain size deduced from
      transmission electron microscopy is 7.5 nm. The hematological parameters
      registered for the rats exposed to D-IONPs at 1 ml/kg have had values
      approximately equal to those examined for the control specimen. The architecture
      of liver and kidneys was not affected after one day of intraperitoneal injection
      of D-IONPs compared to the reference group. After 21 and 28 days respectively
      from the administration of the D-IONPs solution, the liver and kidneys from the
      injected rats showed a normal aspect without abnormalities compared to the rats
      uninjected. Our findings suggest that the administration of 1 ml/kg D-IONPs did
      not cause any toxicological effect since the parameters of renal and liver
      function were in the normal range as reported to the control group. 

PMID- 27045673
TI  - Novel SCN1A variants in Dravet syndrome and evaluating a wide approach of patient
      selection.
AB  - Voltage-gated sodium channels are essential for generation and propagation of the
      action potential mainly in nerve and muscle cells. Causative variants in SCN1A
      gene which codes the main, pore-forming subunit of the channel expressed in
      central nervous system are associated predominantly with Dravet syndrome (DS), as
      well as with generalized epilepsy with febrile seizures plus (GEFS+) making it
      one of the most significant epilepsy gene. Our goal was to determine whether
      SCN1A screening is relevant in patients with a broad range of epileptic
      syndromes. 52 patients diagnosed with DS, generalized epilepsy with GEFS+ or
      similar types of epileptic syndromes were included. Sequencing of the protein
      coding parts of the gene complemented with MLPA analysis was carried out. One
      already described nonsense variant, four novel protein truncating variants and a
      deletion encompassing the whole SCN1A gene were revealed, all in heterozygous
      state. All identified variants were found in DS patients with 85.7% sensitivity,
      thus supporting the role of profound SCN1A gene variants in etiology of DS
      phenotype. No causative variants were identified in any of non-DS epileptic
      patients in our cohort, suggesting a minor, but not irrelevant role for SCN1A in
      patients with other types of childhood epilepsy. 

PMID- 27045674
TI  - New mechanisms of vesicles migration.
AB  - In multicellular organisms, both health and disease are defined by means of
      communication patterns involving the component cells. Despite the intricate
      networks of soluble mediators, cells are also programed to exchange complex
      messages pre-assembled as multimolecular cargo of membranous structures known as
      extracellular vesicles (EVs). Several biogenetic pathways produce EVs with
      different properties able to orchestrate neighboring cell reactions or to
      establish an environment ripe for spreading tumor cells. Such an effect is in
      fact an extension of similar physiological roles played by exosomes in guiding
      cell migration under nontumoral tissue remodeling and organogenesis. We start
      with a biological thought experiment equivalent to Benard's experiment, involving
      a fluid layer of EVs adherent to an extracellular matrix, in a haptotactic
      gradient, then, we build and present the first Lorenz model for EVs migration.
      Using Galerkin's method of reducing a system of partial differential equations to
      a system of ordinary differential equations, a biological Lorenz system is
      developed. Such a physical frame distributing individual molecular or exosomal
      type cell-guiding cues in the extracellular matrix space could serve as a guide
      for tissue neoformation of the budding pattern in nontumoral or tumoral
      instances. 

PMID- 27045675
TI  - Carbon dioxide and methane emissions from the scale model of open dairy lots.
AB  - To investigate the impacts of major factors on carbon loss via gaseous emissions,
      carbon dioxide (CO2) and methane (CH4) emissions from the ground of open dairy
      lots were tested by a scale model experiment at various air temperatures (15, 25,
      and 35  degrees C), surface velocities (0.4, 0.7, 1.0, and 1.2 m sec(-1)), and
      floor types (unpaved soil floor and brick-paved floor) in controlled laboratory
      conditions using the wind tunnel method. Generally, CO2 and CH4 emissions were
      significantly enhanced with the increase of air temperature and velocity (P <
      0.05). Floor type had different effects on the CO2 and CH4 emissions, which were
      also affected by air temperature and soil characteristics of the floor. Although
      different patterns were observed on CH4 emission from the soil and brick floors
      at different air temperature-velocity combinations, statistical analysis showed
      no significant difference in CH4 emissions from different floors (P > 0.05). For
      CO2, similar emissions were found from the soil and brick floors at 15 and 25 
      degrees C, whereas higher rates were detected from the brick floor at 35  degrees
      C (P < 0.05). Results showed that CH4 emission from the scale model was
      exponentially related to CO2 flux, which might be helpful in CH4 emission
      estimation from manure management. IMPLICATIONS: Gaseous emissions from the open
      lots are largely dependent on outdoor climate, floor systems, and management
      practices, which are quite different from those indoors. This study assessed the
      effects of floor types and air velocities on CO2 and CH4 emissions from the open
      dairy lots at various temperatures by a wind tunnel. It provided some valuable
      information for decision-making and further studies on gaseous emissions from
      open lots.

PMID- 27045676
TI  - Complete Stereochemical Assignment of Campechic Acids A and B.
AB  - Campechic acids A and B are anti-invasive polyketide antibiotics isolated from
      Streptomyces sp. CHI93 strain. Herein we describe stereoselective synthesis of
      the C-16-C-30 fragment of campechic acids A and B via a biosynthesis-inspired
      epoxide-opening cascade and its NMR spectroscopic comparison with the authentic
      degradation product, resulting in configurational assignment of the C-21, C-24, C
      25, and C-28 stereogenic centers and reassignment of the C-18 stereogenic center.

PMID- 27045677
TI  - Hexadecenoic Fatty Acid Isomers in Human Blood Lipids and Their Relevance for the
      Interpretation of Lipidomic Profiles.
AB  - Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in
      particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid
      (16:0) affords the delta-9 desaturase index that is increased in obesity.
      Recently, other positional and geometrical MUFA isomers belonging to the
      hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic
      acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work
      we report: i) the identification of sapienic acid as component of human
      erythrocyte membrane phospholipids with significant increase in morbidly obese
      patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the
      first comparison of erythrocyte membrane phospholipids (PL) and plasma
      cholesteryl esters (CE) in morbidly obese patients highlighting that some of
      their fatty acid levels have opposite trends: increases of both palmitic and
      sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in
      red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase
      of palmitoleic acid was similar in both lipid species. Consequentially,
      desaturase enzymatic indexes gave different results, depending on the lipid class
      used for the fatty acid content. The fatty acid profile of morbidly obese
      subjects also showed significant increases of stearic acid (C18:0) and C20 omega
      6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6
      omega-3) as compared with lean healthy controls. Trans monounsaturated and
      polyunsaturated fatty acids were also measured and found significantly increased
      in both lipid classes of morbidly obese subjects. These results highlight the C16
      MUFA isomers as emerging metabolic marker provided that the assignment of the
      double bond position and geometry is correctly performed, thus identifying the
      corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have
      different fatty acid trends, caution must also be used in the choice of lipid
      species for the interpretation of lipidomic profiles. 

PMID- 27045678
TI  - Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype
      Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine
      Model of Trypanosoma cruzi Infection.
AB  - We developed a novel murine model of long-term infection with Trypanosoma cruzi
      with the aim to elucidate the pathogenesis of megacolon and the associated
      adaptive and neuromuscular intestinal disorders. Our intent was to produce a
      chronic stage of the disease since the early treatment should avoid 100%
      mortality of untreated animals at acute phase. Treatment allowed animals to be
      kept infected and alive in order to develop the chronic phase of infection with
      low parasitism as in human disease. A group of Swiss mice was infected with the Y
      strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized
      (acute-phase group) and another sub-group was treated with benznidazole and
      euthanized 15 months after infection (chronic-phase group). Whole colon samples
      were harvested and used for studying the histopathology of the intestinal smooth
      muscle and the plasticity of the enteric nerves. In the acute phase, all animals
      presented inflammatory lesions associated with intense and diffuse parasitism of
      the muscular and submucosa layers, which were enlarged when compared with the
      controls. The occurrence of intense degenerative inflammatory changes and
      increased reticular fibers suggests inflammatory-induced necrosis of muscle
      cells. In the chronic phase, parasitism was insignificant; however, the
      architecture of Auerbach plexuses was focally affected in the inflamed areas, and
      a significant decrease in the number of neurons and in the density of
      intramuscular nerve bundles was detected. Other changes observed included
      increased thickness of the colon wall, diffuse muscle cell hypertrophy, and
      increased collagen deposition, indicating early fibrosis in the damaged areas.
      Mast cell count significantly increased in the muscular layers. We propose a
      model for studying the long-term (15 months) pathogenesis of Chagasic megacolon
      in mice that mimics the human disease, which persists for several years and has
      not been fully elucidated. We hypothesize that the long-term inflammatory process
      mediates neuronal damage and intramuscular and intramural denervation, leading to
      phenotypic changes in smooth muscle cells associated with fibrosis. These long
      term structural changes may represent the basic mechanism for the formation of
      the Chagasic megacolon.

PMID- 27045679
TI  - The importance of the chemical structure of pregnanes in the concurrent
      inhibition of estrous behavior in the female rat.
AB  - An investigation of aspects ranging from behavior to molecular electronic
      structure and physicochemical properties was performed to explore the role of
      5alpha-pregnanedione (5alpha-DHP), 5beta-pregnanedione (5beta-DHP) and their
      precursor progesterone (P) on the concurrent inhibition of the sexual lordosis
      response in female rats. The concurrent inhibition of lordosis behavior occurs
      when ovariectomized rodents are primed simultaneously with estradiol (E2) and P.
      Thus, a second administration of P 40h later fails to induce the expected sexual
      response that takes place when E2 and P are administered sequentially 40h apart.
      In this study, it is hypothesized that the modulation of the sexual behavior
      display depends to some extent on the molecular structure and associated
      physicochemical properties of steroid hormones such as P and its metabolites.
      Therefore, these molecules must be studied chemically and structurally to explain
      their role in sexual behavior, including the concurrent inhibition effect.
      Analysis of the electronic structure and physicochemical properties demonstrated
      striking differences in the A-ring region of P, 5alpha-DHP and 5beta-DHP,
      particularly in atomic charges, dipole moment (DM) and electrostatic potentials.
      Similarly, the structural differences between the trans (5alpha-DHP) and cis
      (5beta-DHP) configurations were remarkable. 5alpha-DHP most significantly
      promoted the concurrent inhibition of the lordosis behavior, followed by P and
      5beta-DHP. These data indicate that variations in pregnane structure are related
      to the extent of the concurrent inhibition effect and also suggest that P may act
      as a prehormone in certain functions of the central nervous system.

PMID- 27045680
TI  - Estrogen signaling and unfolded protein response in breast cancer.
AB  - Activation of the unfolded protein response (UPR) confers resistance to anti
      estrogens and chemotherapeutics in estrogen receptor alpha (ERalpha)-positive and
      triple-negative breast cancers. Among the regulators of the UPR in breast cancer
      is estrogen signaling. Estrogen regulates major components of the UPR and ER
      expression is associated with the sensitivity of tumor cells to UPR-regulated
      apoptosis. Recent studies have confirmed the crosstalk between the ERs and UPR
      and suggest novel therapeutic strategies that combine targeting of both signaling
      pathways. These remedies may be more effective in repressing oncogenic adaptive
      mechanisms and benefit patients with resistant disease.

PMID- 27045682
TI  - Is There a Quadruple Bond in C2?
AB  - The chemical structure of the ground state of C2 has been the subject of intense
      debate after the suggestion that the molecule could exhibit a "fourth" covalent
      bond. In this paper, we investigate this problem explicitly avoiding all the
      points of conflict from the previous papers to show that there is no quadruple
      bond in C2. The generalized product function energy partitioning (GPF-EP) method
      has been applied to calculate the interference energy (IE) that accounts for the
      formation of covalent bonds for each bond of the molecule. The IE analysis shows
      that for the standard sigma and pi bonds interference exhibits the expected
      behavior, while for the "fourth" bond interference is a destabilizing factor. To
      make sure this could not be attributed to a new kind of bond, we performed an
      equivalent analysis for the (3)Sigma(-) excited state of C3 molecule in which
      similar "bonding" occurs between the two ending carbon atoms. We also show that
      the difference in force constants of C2 and acetylene can be rationalized in
      terms of the amount of charge density in the internuclear region by looking at
      the changes in the overlaps between orbitals along the bond axis. 

PMID- 27045681
TI  - The Impact of Enrolment in Methadone Maintenance Therapy on Initiation of Heavy
      Drinking among People Who Use Heroin.
AB  - BACKGROUND: There is equivocal evidence regarding whether people who use heroin
      substitute heroin for alcohol upon entry to methadone maintenance therapy (MMT).
      We aimed to examine the impact of MMT enrolment on the onset of heavy drinking
      among people who use heroin. METHODS: We derived data from prospective, community
      based cohorts of people who inject drugs in Vancouver, Canada, between December
      1, 2005, and May 31, 2014. Multivariable extended Cox regression analysis
      examined the effect of MMT enrolment on the onset of heavy drinking among people
      who used heroin at baseline. RESULTS: In total, 357 people who use heroin were
      included in this study. Of these, 208 (58%) enrolled in MMT at some point during
      follow-up, and 115 (32%) reported initiating heavy drinking during follow-up for
      an incidence density of 7.8 events (95% CI 6.4-9.5) per 100 person-years. The
      incidence density of heavy drinking was significantly lower among those enrolled
      in MMT at some point during follow-up compared to those who did not (4.6 vs.
      16.2; p < 0.001). MMT enrolment was not significantly associated with time to
      initiate heavy drinking (adjusted relative hazard (ARH) 1.27; 95% CI 0.78-2.07)
      after adjustment for relevant demographic and substance-use characteristics. Age
      and cannabis use were the only variables that were independently associated with
      the time to onset of heavy drinking (ARH 0.74; 95% CI 0.58-0.94 and ARH 2.06; 95%
      CI 1.32-3.19, respectively). CONCLUSION: In this study, MMT enrolment did not
      predict heavy drinking and may even appear to decrease the initiation of heavy
      drinking. Our findings suggest younger age and cannabis use may predict heavy
      drinking. These findings could help inform on-going discussions about the effects
      of opioid agonist therapy on alcohol consumption among people who use heroin.

PMID- 27045683
TI  - Bacteriophage Tailspikes and Bacterial O-Antigens as a Model System to Study Weak
      Affinity Protein-Polysaccharide Interactions.
AB  - Understanding interactions of bacterial surface polysaccharides with receptor
      protein scaffolds is important for the development of antibiotic therapies. The
      corresponding protein recognition domains frequently form low-affinity complexes
      with polysaccharides that are difficult to address with experimental techniques
      due to the conformational flexibility of the polysaccharide. In this work, we
      studied the tailspike protein (TSP) of the bacteriophage Sf6. Sf6TSP binds and
      hydrolyzes the high-rhamnose, serotype Y O-antigen polysaccharide of the Gram
      negative bacterium Shigella flexneri (S. flexneri) as a first step of
      bacteriophage infection. Spectroscopic analyses and enzymatic cleavage assays
      confirmed that Sf6TSP binds long stretches of this polysaccharide. Crystal
      structure analysis and saturation transfer difference (STD) NMR spectroscopy
      using an enhanced method to interpret the data permitted the detailed description
      of affinity contributions and flexibility in an Sf6TSP-octasaccharide complex.
      Dodecasaccharide fragments corresponding to three repeating units of the O
      antigen in complex with Sf6TSP were studied computationally by molecular dynamics
      simulations. They showed that distortion away from the low-energy solution
      conformation found in the octasaccharide complex is necessary for ligand binding.
      This is in agreement with a weak-affinity functional polysaccharide-protein
      contact that facilitates correct placement and thus hydrolysis of the
      polysaccharide close to the catalytic residues. Our simulations stress that the
      flexibility of glycan epitopes together with a small number of specific protein
      contacts provide the driving force for Sf6TSP-polysaccharide complex formation in
      an overall weak-affinity interaction system.

PMID- 27045684
TI  - Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin
      Mono-Resistant Pulmonary Tuberculosis in Lima, Peru.
AB  - BACKGROUND: Isoniazid and rifampicin are the two most efficacious first-line
      agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid
      and rifampicin mono-resistance, associated risk factors, and the association of
      mono-resistance on treatment outcomes. METHODS: A prospective, observational
      cohort study enrolled adults with a first episode of smear-positive pulmonary TB
      from 34 health facilities in a northern district of Lima, Peru, from March 2010
      through December 2011. Participants were interviewed and a sputum sample was
      cultured on Lowenstein-Jensen (LJ) media. Drug susceptibility testing was
      performed using the proportion method. Medication regimens were documented for
      each patient. Our primary outcomes were treatment outcome at the end of
      treatment. The secondary outcome included recurrent episodes among cured patients
      within two years after completion of the treatment. RESULTS: Of 1292 patients
      enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid
      mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance
      was present in 24 (2%) patients. In the multivariate logistic regression model,
      isoniazid mono-resistance was associated with illicit drug use (adjusted odds
      ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1-4.1), and rifampicin mono
      resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9-47.8).
      Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes
      including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%,
      p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%,
      p<0.01). CONCLUSION: A high prevalence of isoniazid and rifampicin mono
      resistance was found among TB patients in our low HIV burden setting which were
      similar to regions with high HIV burden. Patients with isoniazid and rifampicin
      mono-resistance had an increased risk of poor treatment outcomes.

PMID- 27045685
TI  - Interrelationships between trait anxiety, situational stress and mental effort
      predict phonological processing efficiency, but not effectiveness.
AB  - Attentional control theory (ACT) describes the mechanisms associated with the
      relationship between anxiety and cognitive performance. We investigated the
      relationship between cognitive trait anxiety, situational stress and mental
      effort on phonological performance using a simple (forward-) and complex
      (backward-) word span task. Ninety undergraduate students participated in the
      study. Predictor variables were cognitive trait anxiety, indexed using
      questionnaire scores; situational stress, manipulated using ego threat
      instructions; and perceived level of mental effort, measured using a visual
      analogue scale. Criterion variables (a) performance effectiveness (accuracy) and
      (b) processing efficiency (accuracy divided by response time) were analyzed in
      separate multiple moderated-regression analyses. The results revealed (a) no
      relationship between the predictors and performance effectiveness, and (b) a
      significant 3-way interaction on processing efficiency for both the simple and
      complex tasks, such that at higher effort, trait anxiety and situational stress
      did not predict processing efficiency, whereas at lower effort, higher trait
      anxiety was associated with lower efficiency at high situational stress, but not
      at low situational stress. Our results were in full support of the assumptions of
      ACT and implications for future research are discussed. (PsycINFO Database Record

PMID- 27045686
TI  - Heterogeneity of long-history migration predicts emotion recognition accuracy.
AB  - Recent work (Rychlowska et al., 2015) demonstrated the power of a relatively new
      cultural dimension, historical heterogeneity, in predicting cultural differences
      in the endorsement of emotion expression norms. Historical heterogeneity
      describes the number of source countries that have contributed to a country's
      present-day population over the last 500 years. People in cultures originating
      from a large number of source countries may have historically benefited from
      greater and clearer emotional expressivity, because they lacked a common language
      and well-established social norms. We therefore hypothesized that in addition to
      endorsing more expressive display rules, individuals from heterogeneous cultures
      will also produce facial expressions that are easier to recognize by people from
      other cultures. By reanalyzing cross-cultural emotion recognition data from 92
      papers and 82 cultures, we show that emotion expressions of people from
      heterogeneous cultures are more easily recognized by observers from other
      cultures than are the expressions produced in homogeneous cultures. Heterogeneity
      influences expression recognition rates alongside the individualism-collectivism
      of the perceivers' culture, as more individualistic cultures were more accurate
      in emotion judgments than collectivistic cultures. This work reveals the present
      day behavioral consequences of long-term historical migration patterns and
      demonstrates the predictive power of historical heterogeneity. (PsycINFO Database
      Record

PMID- 27045687
TI  - Identification of four new gene members of the KAP6 gene family in sheep.
AB  - KAP6 is a high glycine-tyrosine keratin-associated protein (HGT-KAP) family. This
      family is thought to contain multiple genes. In this study, we used a KRTAP6
      coding sequence to search the Ovine Genome (v3.1) and identified five homologous
      regions (R1-R5). All these regions contained an open reading frame, and they were
      either identical to, or highly similar to, sheep skin Expressed Sequence Tags
      (ESTs). Phylogenetic analysis revealed that R1-R5 were clustered with KAP6
      sequences from different species and formed a group distinct to other HGT-KAPs.
      R1 was very similar to the characterised KRTAP6-1 sequence, but the remaining
      genes appeared to be new. PCR primers were designed to amplify and confirm the
      presence of these new genes. Amplicons were obtained for all of the 96 sheep
      investigated. Six, five, three and six PCR-SSCP patterns representing six, five,
      three and six DNA sequences were observed for KRTAP6-2 to KRTAP6-5 respectively.
      KRTAP6-2 and KRTAP6-4 had five and three SNPs respectively. Three SNPs and a 45
      bp insertion/deletion were detected for KRTAP6-3, and five SNPs and an 18-bp
      insertion/deletion were identified for KRTAP6-5. Allele frequencies for these
      KAP6 genes differed between Merino and Romney sheep. 

PMID- 27045688
TI  - Ideonella sakaiensis sp. nov., isolated from a microbial consortium that degrades
      poly(ethylene terephthalate).
AB  - A Gram-stain-negative, aerobic, non-spore-forming, rod-shaped bacterium, designed
      strain 201-F6T, was isolated from a microbial consortium that degrades
      poly(ethylene terephthalate) (PET) collected in Sakai city, Japan, and was
      characterized on the basis of a polyphasic taxonomic study. The cells were motile
      with a polar flagellum. The strain contained cytochrome oxidase and catalase. It
      grew within the pH range 5.5-9.0 (optimally at pH 7-7.5) and at 15-42 oC
      (optimally at 30-37 oC). The major isoprenoid quinone was ubiquinone with eight
      isoprene units (Q-8). C16 : 0, C17 : 0 cyclo, C18 :1omega7c and C12 : 0 2-OH were
      the predominant cellular fatty acids. The major polar lipids were
      phosphatidylethanolamine, lyso-phosphatidylethanolamine, phosphatidylglycerol and
      diphosphatidylglycerol. The G+C content of genomic DNA was 70.4 mol%.
      Phylogenetic analysis using the 16S rRNA gene sequences showed that strain 201
      F6T was affiliated to the genus Ideonella, and was closely related to Ideonella
      dechloratans LMG 28178T (97.7 %) and Ideonella azotifigens JCM 15503T (96.6 %).
      Strain 201-F6T could be clearly distinguished from the related species of the
      genus Ideonella by its physiological and biochemical characteristics as well as
      by its phylogenetic position and DNA-DNA relatedness. Therefore, the strain
      represents a novel species of the genus Ideonella, for which the name Ideonella
      sakaiensis sp. nov. (type strain 201-F6T=NBRC 110686T=TISTR 2288T) is proposed. 

PMID- 27045689
TI  - Effect of dystocia on subsequent reproductive performance and functional
      longevity in Holstein cows.
AB  - The objective of this study was to evaluate the effect of dystocia on the
      reproductive performance and functional longevity in Iranian Holsteins. Data
      consisted of 1 467 064 lactation records of 581 421 Holstein cows from 3083 herds
      which were collected by the Animal Breeding Center of Iran from April 1987 to
      February 2014. Reproduction traits in this study included interval from first to
      second calving, days open and days from first calving to first service. The
      generalized linear model was used for the statistical analysis of reproductive
      traits. Survival analysis was performed using the Weibull proportional hazards
      models to analyse the impact of dystocia on functional longevity. The incidence
      of dystocia had an adverse effect on the reproductive performance of dairy cows.
      Therefore, reproductive traits deteriorated along with increase in dystocia score
      (p < 0.05). The culling risk was increased along with increase in the score of
      dystocia (p < 0.0001). The greatest culling risk was observed in primiparous
      cows, small herds and low-yielding cows (p < 0.0001). Also, the lowest culling
      risk was found for cows calving at the youngest age (<27 months), and cows with
      age at first calving >33 months had the greatest risk (p < 0.0001). The results
      of current study indicated that dystocia had important negative effects on the
      reproductive performance and functional longevity in dairy cows, and it should be
      avoided as much as possible to provide a good perspective in the scope of
      economic and animal welfare issues in dairy herds. 

PMID- 27045690
TI  - Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel
      Disease.
AB  - Studies in transgenic murine models have provided insight into the complexity
      underlying inflammatory bowel disease (IBD), a disease hypothesized to result
      from an injurious immune response against intestinal microbiota. We recently
      developed a mouse model of IBD that phenotypically and histologically resembles
      human childhood-onset ulcerative colitis (UC), using mice that are genetically
      modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice). Here we
      report the effects of early life onset of colon inflammation on growth and
      reproductive performance of T/I mice. T/I dams with colitis often failed to get
      pregnant or had small litters with pups that failed to thrive. Production was
      optimized by breeding double homozygous mutant T/I males to females homozygous
      mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het"
      dams) that were not susceptible to spontaneous colon inflammation. When born to
      healthy (T/I-het) dams, T/I pups initially gained weight similarly to wild type
      (WT) pups and to their non-colitis-susceptible T/I-het littermates. However,
      their growth curves diverged between 8 and 13 weeks, when most T/I mice had
      developed moderate to severe colitis. The observed growth failure in T/I mice
      occurred despite a significant increase in their food consumption and in the
      absence of protein loss in the stool. This was not due to TNF-induced anorexia or
      altered food consumption due to elevated leptin levels. Metabolic studies
      demonstrated increased consumption of oxygen and water and increased production
      of heat and CO2 in T/I mice compared to their T/I-het littermates, without
      differences in motor activity. Based on the clinical similarities of this early
      life onset model of IBD in T/I mice to human IBD, these results suggest that
      mechanisms previously hypothesized to explain growth failure in children with IBD
      require re-evaluation. The T/I mouse model may be useful for further
      investigation of such mechanisms and for development of therapies to prevent
      reproductive complications and/or growth failure in humans with IBD. 

PMID- 27045691
TI  - Acid-mediated topological control in a functionalized foldamer.
AB  - Induced conformational change provides a powerful mechanism to modulate the
      structure and function of molecules. Here we describe the synthesis of chiral,
      surface-functionalized oligomeric pyridine/imidazolidin-2-one foldamers, and
      interrogate their acid-mediated transition between linear and helical topologies.

PMID- 27045692
TI  - Photoinduced inhibition of DNA unwinding in vitro with water-soluble polymers
      containing both phosphorylcholine and photoreactive groups.
AB  - Nile blue (NB)-tagged DNA helix-targeting amphiphilic photoreactive 2
      methacryloyloxyethyl phosphorylcholine (MPC) polymer, poly(MPC-co-3
      methacryloyloxy-2-hydroxypropyl-4-oxybenzophenone-co-2-trimethylammonium ethyl
      methacrylate chloride) (PMHT-NB), containing a cationic group to facilitate cell
      membrane penetration and a benzophenone (BP) group to promote photoinduced
      conjugation with DNA helix was synthesized using radical polymerization method.
      Ultraviolet light (UV)-visible light absorption spectra of PMHT-NB showed
      absorption peaks at wavelengths 254, 289, and 600nm, suggesting successful
      incorporation of BP and NB groups. PMHT-NB was highly sensitive to
      photoirradiation with UV irradiation at the second level, as confirmed based on
      the degradation spectra of UV absorption peaks for the BP group in PBS (pH=7.4).
      PMHT-NB showed good solubility in both aqueous solution and in ethanol. In a cell
      culture medium containing 10mg/mL PMHT-NB, the NB group showed fluorescence peaks
      at an emission wavelength of 650nm and excitation wavelength of 633nm. PMHT-NB
      also showed low cytotoxicity and good cell membrane permeability toward cancerous
      HeLa cells. Further, photoinduced PMHT-NB effectively inhibited the unwinding of
      a molecular beacon with a hairpin structure, indicating that synthetic
      photoreactive MPC polymers photoregulated the unwinding of DNA. STATEMENT OF
      SIGNIFICANCE: Natural and synthetic genetic hybrid biomaterials consisting of
      well-designed polymers loaded with oligonucleotide fragments are considered as an
      attractive alternative to conventional transgene systems and chemical methods for
      precisely and rapidly modulation of intracellular gene expression. Containing
      versatile functional moieties, the effectiveness of well-designed cytocompatible
      polymers themselves without oligonucleotide fragments on gene regulation is
      rarely investigated. In the present study, a 2-methacryloyloxyethyl
      phosphorylcholine (MPC) polymer composed of a tumor/DNA-targeting moiety and
      photo-controllable unit demonstrated low cytotoxicity, rapid cell membrane
      permeability and effective inhibitive ability on DNA unwinding under a light
      irradiation. The synthetic polymer was considered as promising material to
      effectively inhibit intracellular partial DNA unwinding for cancer/gene therapy.

PMID- 27045693
TI  - In vivo monitoring the biodegradation of magnesium alloys with an electrochemical
      H2 sensor.
AB  - Monitoring the biodegradation process of magnesium and its alloys in vivo is
      challenging. Currently, this process is monitored by micro-CT and X-ray imaging
      in vivo, which require large and costly instrumentation. Here we report a simple
      and effective methodology to monitor the biodegradation process in vivo by
      sensing H2 transdermally above a magnesium sample implanted subcutaneously in a
      mouse. An electrochemical H2 microsensor was used to measure the biodegradation
      product H2 at the surface of the skin for two magnesium alloys (ZK40 and AZ31)
      and one high purity magnesium single crystal (Mg8H). The sensor was able to
      easily detect low levels of H2 (30-400MUM) permeating through the skin with a
      response time of about 30s. H2 levels were correlated with the biodegradation
      rate as determined from weight loss measurements of the implants. This new method
      is noninvasive, fast and requires no major equipment. STATEMENT OF SIGNIFICANCE:
      Biomedical devices such as plates and screws used for broken bone repair are
      being developed out of biodegradable magnesium alloys that gradually dissolve
      when no longer needed. This avoids subsequent removal by surgery, which may be
      necessary if complications arise. A rapid, non-invasive means for monitoring the
      biodegradation process in vivo is needed for animal testing and point of care
      (POC) evaluation of patients. Here we report a novel, simple, fast, and
      noninvasive method to monitor the biodegradation of magnesium in vivo by
      measuring the biodegradation product H2 with an electrochemical H2 sensor. Since
      H2 rapidly permeates through biological tissue, measurements are made by simply
      pressing the sensor tip against the skin above the implant; the response is
      within 30s.

PMID- 27045694
TI  - Interrogation of Patient Smartphone Activity Tracker to Assist Arrhythmia
      Management.
AB  - A 42-year-old man presented to the emergency department (ED) with newly diagnosed
      atrial fibrillation of unknown duration. Interrogation of the patient's wrist
      worn activity tracker and smartphone application identified the onset of the
      arrhythmia as within the previous 3 hours, permitting electrocardioversion and
      discharge of the patient from the ED.

PMID- 27045695
TI  - Species identification of the shark involved in the 2007 Lifou fatal attack on a
      swimmer: A reply to Tirard et al. (2015).
AB  - Based on new photographs of the wound, Tirard et al. (2015) tried to demonstrate
      that the shark involved in a fatal attack on a human in Lifou in 2007 had
      homodont teeth and that it sawed the femur instead of directly cutting it,
      promoting the hypothesis that it was a tiger shark instead of a white shark. They
      also contested the data provided by the direct witness of the attack about the
      behaviour of the shark, specific to this former species. The evidences they
      provide are not convincing and, based on the absence of tissue loss and
      description of a jumping behaviour, we still believe that it was a single bite
      and-spit attack by a white shark.

PMID- 27045696
TI  - Contrafreeloading, reinforcement rate, and behavioral momentum.
AB  - Contrafreeloading involves organisms working for food when an identical source of
      food is freely available. The present study assessed whether training
      reinforcement rates influenced contrafreeloading by arranging a within-subject
      and within-session design using pigeons. Across different alternating
      discriminative stimuli, variable-interval schedules arranged leaner (30 per hour)
      and richer (120 per hour) rates of food reinforcement. Responding decreased but
      persisted in the presence of free food during the session (i.e.,
      contrafreeloading). Further, responding tended to be similar between components
      initially but greater persistence emerged in the richer component with additional
      exposure. With pre-session feeding, responding did not change systematically
      across test sessions and tended to be more persistent in the richer component.
      Greater persistence with greater training reinforcement rates is generally
      consistent with an influential theory of response persistence, behavioral
      momentum theory. However, the different patterns of responding across test
      sessions between pre- and within-session feeding reveals multiple behavioral
      processes involved in contrafreeloading that have yet to be fully understood.
      Behavioral momentum theory could provide a useful theoretical framework for
      understanding and quantifying the behavioral processes underlying
      contrafreeloading. 

PMID- 27045697
TI  - The effects of smoking on whisker movements: A quantitative measure of
      exploratory behaviour in rodents.
AB  - Nicotine, an important component of cigarette smoke, is a neurotransmitter that
      contributes to stress, depression and anxiety in smokers. In rodents, it
      increases anxiety and reduces exploratory behaviours. However, so far, the
      measurements of exploratory behaviour in rodents have only been semi-quantitative
      and lacking in sufficient detail to characterise the temporal effect of smoking
      cessation. As rodents, such as mice and rats, primarily use whiskers to explore
      their environment, we studied the effect of 3 months smoking with 1 and 2 weeks
      smoking cessation on whisker movements in mice, using high-speed video camera
      footage and image analysis. Both protraction and retraction whisker velocities
      were increased in smoking mice (p<0.001) and returned to normal following just
      one week of smoking cessation. In addition, locomotion speeds were decreased in
      smoking mice, and returned to normal following smoking cessation. Lung function
      was also impacted by smoking and remained impaired even following smoking
      cessation. We suggest that the increased whisker velocities in the smoking mice
      reflect reduced exploration and impeded tactile performance. The increase in
      whisker velocity with smoking, and its reduction following smoking cessation,
      also lends support to acetylcholine being involved in awareness, attention and
      alertness pathways. It also shows that smoking-induced behavioural changes can be
      reversed with smoking cessation, which may have implications for human smokers. 

PMID- 27045698
TI  - Novel 3D light microscopic analysis of IUGR placentas points to a morphological
      correlate of compensated ischemic placental disease in humans.
AB  - The villous tree of the human placenta is a complex three-dimensional (3D)
      structure with branches and nodes at the feto-maternal border in the key area of
      gas and nutrient exchange. Recently we introduced a novel, computer-assisted 3D
      light microscopic method that enables 3D topological analysis of branching
      patterns of the human placental villous tree. In the present study we applied
      this novel method to the 3D architecture of peripheral villous trees of placentas
      from patients with intrauterine growth retardation (IUGR placentas), a severe
      obstetric syndrome. We found that the mean branching angle of branches in
      terminal positions of the villous trees was significantly different statistically
      between IUGR placentas and clinically normal placentas. Furthermore, the mean
      tortuosity of branches of villous trees in directly preterminal positions was
      significantly different statistically between IUGR placentas and clinically
      normal placentas. We show that these differences can be interpreted as
      consequences of morphological adaptation of villous trees between IUGR placentas
      and clinically normal placentas, and may have important consequences for the
      understanding of the morphological correlates of the efficiency of the placental
      villous tree and their influence on fetal development. 

PMID- 27045699
TI  - Seasonal and Weather Effects on Older Drivers' Trip Distances.
AB  - The purpose of this study was to determine if season or weather affected the
      objectively measured trip distances of older drivers (>= 70 years; n = 279) at
      seven Canadian sites. During winter, for all trips taken, trip distance was 7 per
      cent shorter when controlling for site and whether the trip occurred during the
      day. In addition, for trips taken within city limits, trip distance was 1 per
      cent shorter during winter and 5 per cent longer during rain when compared to no
      precipitation when controlling for weather (or season respectively), time of day,
      and site. At night, trip distance was about 30 per cent longer when controlling
      for season and site (and weather), contrary to expectations. Together, these
      results suggest that older Canadian drivers alter their trip distances based on
      season, weather conditions, and time of day, although not always in the expected
      direction.

PMID- 27045700
TI  - Effects of ospemifene on bone parameters including clinical biomarkers in
      postmenopausal women.
AB  - OBJECTIVE: Ospemifene is an estrogen-receptor agonist/antagonist (also known as a
      selective estrogen-receptor modulator) that is FDA approved for the treatment of
      moderate-to-severe dyspareunia, a symptom of vulvovaginal atrophy, due to
      menopause. Preclinical and clinical data suggest that ospemifene may also have an
      effect on bone health in postmenopausal women. METHODS: Relevant articles,
      including cellular and preclinical studies and clinical trials written in English
      pertaining to ospemifene and bone health, were identified from a database search
      of PubMed (from its inception to June 2015) and summarized in this comprehensive
      review. RESULTS: In vitro data suggest that ospemifene may mediate a positive
      effect on bone through osteoblasts. Ospemifene effectively reduced bone loss and
      resorption in ovariectomized rats, with activity comparable to estradiol and
      raloxifene. Clinical data from three phase 1 or 2 clinical trials (2 placebo- and
      1 raloxifene-controlled) found ospemifene 60 mg/d to have a positive effect on
      the biochemical markers for bone turnover in healthy, postmenopausal women with
      significant improvements relative to placebo and comparable to raloxifene.
      CONCLUSIONS: Ospemifene 60 mg/d may have a protective effect on the bone health
      of women being treated for dyspareunia. The initial clinical data for ospemifene
      follows a trend similar to raloxifene and bazedoxifene, suggesting that
      ospemifene may have bone-protective effects in postmenopausal women. However,
      additional rigorous clinical trials are necessary to confirm any positive effects
      ospemifene may have on vertebral fractures and bone mineral density in healthy
      and osteoporotic women.

PMID- 27045701
TI  - Spectral response in reversing coronary artery atherosclerosis with vitamin D
      supplementation in postmenopausal cynomolgus monkeys.

PMID- 27045702
TI  - Primary ovarian insufficiency associated with autosomal abnormalities: from
      chromosome to genome-wide and beyond.
AB  - OBJECTIVE: The pathophysiology of primary ovarian insufficiency (POI) is not well
      elucidated. Many candidate genetic aberrations are on the X-chromosome; on the
      contrary, many genetic perturbations are also on the autosomes. The aim of this
      review is to summarize the knowledge of genetic aberrations on autosomes from
      chromosomal rearrangement, gene abnormality, genome-wide association studies and
      epigenetics. METHODS: Searches of electronic databases were performed. Articles
      and abstracts relevant to POI and genetic studies associated with autosomes were
      summarized in this interpretive literature review. RESULTS: Various genetic
      aberrations located on the autosomes were found. These abnormalities are from
      chromosomal rearrangement, which might disrupt the critical region on chromosome
      loci or disturbance of the meiosis process. Specific gene aberrations are also
      identified. The genes that have functions in ovarian development,
      folliculogenesis, and steroidogenesis on autosomes are proposed to be involved
      from gene association studies. Gene-to-gene interaction or epistasis also might
      play a role in POI occurrence. Recently, genetic techniques to study the whole
      genome have emerged. Although no specific conclusion has been made, the studies
      using genome-wide association to find the specific aberration throughout the
      genome in POI have been published. Epigenetic mechanisms might also take part in
      the pathogenesis of POI. CONCLUSIONS: The considerably complex process of POI is
      still not well understood. Further research is needed for gene functional
      validation studies to confirm the contribution of genes in POI, or additional
      genome-wide association studies using novel clustered regularly interspaced short
      palindromic repeat/Cas9 technique might make these mechanisms more
      comprehensible.

PMID- 27045703
TI  - Chlorpromazine versus atypical antipsychotic drugs for schizophrenia.
AB  - BACKGROUND: Chlorpromazine is an aliphatic phenothiazine, which is one of the
      widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its
      efficacy and one of the most tested first generation antipsychotic drugs. It has
      been used as a 'gold standard' to compare the efficacy of older and newer
      antipsychotic drugs. Expensive new generation drugs are heavily marketed
      worldwide as a better treatment for schizophrenia, but this may not be the case
      and an unnecessary drain on very limited resources. OBJECTIVES: To compare the
      effects of chlorpromazine with atypical or second generation antipsychotic drugs,
      for the treatment of people with schizophrenia. SEARCH METHODS: We searched the
      Cochrane Schizophrenia Group's Trials Register up to 23 September 2013. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) that compared
      chlorpromazine with any other atypical antipsychotic drugs for treating people
      with schizophrenia. Adults (as defined in each trial) diagnosed with
      schizophrenia, including schizophreniform, schizoaffective and delusional
      disorders were included in this review. DATA COLLECTION AND ANALYSIS: At least
      two review authors independently screened the articles identified in the
      literature search against the inclusion criteria and extracted data from included
      trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and
      the 95% confidence intervals (CIs). For continuous data, we determined the mean
      difference (MD) values and 95% CIs. We assessed the risk of bias in included
      studies and rated the quality of the evidence using the GRADE approach. MAIN
      RESULTS: This review includes 71 studies comparing chlorpromazine to olanzapine,
      risperidone or quetiapine. None of the included trials reported any data on
      economic costs. 1. Chlorpromazine versus olanzapineIn the short term, there
      appeared to be a significantly greater clinical response (as defined in each
      study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to
      3.99, low quality evidence). There was no difference between drugs for relapse (1
      RCT, N = 70; RR 1.5, 95% CI 0.46 to 4.86, very low quality evidence), nor in
      average endpoint score using the Brief Psychiatric Rating Scale (BPRS) for mental
      state (4 RCTs, N = 245; MD 3.21, 95% CI -0.62 to 7.05,very low quality evidence).
      There were significantly more extrapyramidal symptoms experienced amongst people
      receiving chlorpromazine (2 RCTs, N = 298; RR 34.47, 95% CI 4.79 to 248.30,very
      low quality evidence). Quality of life ratings using the general quality of life
      interview (GQOLI) - physical health subscale were more favourable with people
      receiving olanzapine (1 RCT, N = 61; MD -10.10, 95% CI -13.93 to -6.27, very low
      quality evidence). There was no difference between groups for people leaving the
      studies early (3 RCTs, N = 139; RR 1.69, 95% CI 0.45 to 6.40, very low quality
      evidence). 2. Chlorpromazine versus risperidoneIn the short term, there appeared
      to be no difference in clinical response (as defined in each study) between
      chlorpromazine or risperidone (7 RCTs, N = 475; RR 0.84, 95% CI 0.53 to 1.34, low
      quality of evidence), nor in average endpoint score using the BPRS for mental
      state 4 RCTs, N = 247; MD 0.90, 95% CI -3.49 to 5.28, very low quality evidence),
      or any observed extrapyramidal adverse effects (3 RCTs, N = 235; RR 1.7, 95% CI
      0.85 to 3.40,very low quality evidence). Quality of life ratings using the QOL
      scale were significantly more favourable with people receiving risperidone (1
      RCT, N = 100; MD -14.2, 95% CI -20.50 to -7.90, very low quality evidence). There
      was no difference between groups for people leaving the studies early (one RCT, N
      = 41; RR 0.21, 95% CI 0.01 to 4.11, very low quality evidence). 3. Chlorpromazine
      versus quetiapineIn the short term, there appeared to be no difference in
      clinical response (as defined in each study) between chlorpromazine or quetiapine
      (28 RCTs, N = 3241; RR 0.93, 95% CI 0.81 to 1.06, moderate quality evidence) nor
      in average endpoint score using the BPRS for mental state (6 RCTs, N = 548; MD 
      0.18, 95% CI -1.23 to 0.88, very low quality evidence). Quality of life ratings
      using the GQOL1-74 scale were significantly more favourable with people receiving
      quetiapine (1 RCT, N = 59; MD -6.49, 95% CI -11.30 to -1.68, very low quality
      evidence). Significantly more people receiving chlorpromazine experienced
      extrapyramidal adverse effects (8 RCTs, N = 644; RR 8.03, 95% CI 4.78 to 13.51,
      low quality of evidence). There was no difference between groups for people
      leaving the studies early in the short term (12 RCTs, N = 1223; RR 1.04, 95% CI
      0.77 to 1.41,moderate quality evidence). AUTHORS' CONCLUSIONS: Most included
      trials included inpatients from hospitals in China. Therefore the results of this
      Cochrane review are more applicable to the Chinese population. Mostincluded
      trials were short term studies, therefore we cannot comment on the medium and
      long term use of chlorpromazine compared to atypical antipsychotics. Low qualityy
      evidence suggests chlorpromazine causes more extrapyramidal adverse effects.
      However, all studiesused varying dose ranges, and higher doses would be expected
      to be associated with more adverse events.

PMID- 27045704
TI  - Mechanisms of protein homeostasis in health, aging and disease.
AB  - When emerging from the ribosomes, new polypeptides need to fold properly,
      eventually translocate, and then assemble into stable, yet functionally flexible
      complexes. During their lifetime, native proteins are often exposed to stresses
      that can partially unfold and convert them into stably misfolded and aggregated
      species, which can in turn cause cellular damage and propagate to other cells. In
      animal cells, especially in aged neurons, toxic aggregates may accumulate, induce
      cell death and lead to tissue degeneration via different mechanisms, such as
      apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The
      main cellular mechanisms effectively controlling protein homeostasis in youth and
      healthy adulthood are: (1) the molecular chaperones, acting as aggregate
      unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as
      aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as
      aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate
      degrading organelles. For unclear reasons, these cellular defences become
      gradually incapacitated with age, leading to the onset of degenerative diseases.
      Understanding these mechanisms and the reasons for their incapacitation in late
      adulthood is key to the design of new therapies against the progression of aging,
      degenerative diseases and cancers.

PMID- 27045705
TI  - Current status of urban wastewater treatment plants in China.
AB  - The study reported and analyzed the current state of wastewater treatment plants
      (WWTPs) in urban China from the perspective of treatment technologies, pollutant
      removals, operating load and effluent discharge standards. By the end of 2013,
      3508 WWTPs have been built in 31 provinces and cities in China with a total
      treatment capacity of 1.48*10(8)m(3)/d. The uneven population distribution
      between China's east and west regions has resulted in notably different economic
      development outcomes. The technologies mostly used in WWTPs are AAO and oxidation
      ditch, which account for over 50% of the existing WWTPs. According to statistics,
      the efficiencies of COD and NH3-N removal are good in 656 WWTPs in 70 cities. The
      overall average COD removal is over 88% with few regional differences. The
      average removal efficiency of NH3-N is up to 80%. Large differences exist between
      the operating loads applied in different WWTPs. The average operating loading
      rate is approximately 83%, and 52% of WWTPs operate at loadings of <80%, treating
      up to 40% of the wastewater generated. The implementation of discharge standards
      has been low. Approximately 28% of WWTPs that achieved the Grade I-A Discharge
      Standard of Pollutants for Municipal Wastewater Treatment Plant (GB 18918-2002)
      were constructed after 2010. The sludge treatment and recycling rates are only
      25%, and approximately 15% of wastewater is inefficiently treated. Approximately
      60% of WWTPs have capacities of 1*10(4)m(3)/d-5*10(4)m(3)/d. Relatively high
      energy consumption is required for small-scale processing, and the utilization
      rate of recycled wastewater is low. The challenges of WWTPs are discussed with
      the aim of developing rational criteria and appropriate technologies for water
      recycling. Suggestions regarding potential technical and administrative measures
      are provided.

PMID- 27045706
TI  - An assessment of dioxin exposure across gestation and lactation using a PBPK
      model and new data from Seveso.
AB  - On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up
      to 30kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-the most potent dioxin
      congener. Twenty years later, the Seveso Women's Health Study (SWHS) initiated a
      follow-up assessment of a cohort of female Seveso residents. Researchers
      collected serial blood, measured for TCDD levels, and recorded information about
      the women's medical history after the explosion. The study's aims were to: 1)
      modify the human PBPK model for TCDD (Emond et al. 2004; Emond et al. 2005; NCEA
      USEPA, 2010) to include repetitive gestation and lactation; 2) simulate TCDD
      blood concentrations during different life stages including pregnancy and
      lactation, under different exposure scenarios; and 3) use this PBPK model to
      compare the influence of gestation and lactation on elimination of TCDD. After
      optimization of the model, it was assessed using data from the SWHS cohort. The
      23 women in Subcohort A, were 4-39years old and in Subcohort B, the 18 women were
      3-17years old when the explosion occurred. The model accurately predicted the
      blood concentrations during the 20years post-exposure, including periods of
      pregnancy and lactation. The model was also used to analyze the contribution of
      gestation and lactation to the mother's elimination of TCDD. The results suggest
      that gestation and lactation do not significantly impact TCDD blood elimination.
      Future efforts will focus on using additional data to evaluate the PBPK model and
      improving the mathematical descriptions of lactation and multiple gestations.

PMID- 27045707
TI  - Comparison of Scoring Systems in Pediatric Mini-Percutaneous Nephrolithotomy.
AB  - OBJECTIVE: To apply urolithiasis scoring systems to the pediatric miniperc
      procedure and to compare their predictive capability for postoperative outcomes.
      MATERIALS AND METHODS: Records from 2 referral centers of patients under 18 years
      of age who had the miniperc procedure between 2010 and 2015 were retrospectively
      investigated. All patients included in the study were graded by the same surgeon
      according to Guy's and Clinical Research Office of the Endourological Society
      (CROES) scoring systems using preoperative imaging methods. Patient demographics
      and outcomes were compared according to the complexity of the procedure as graded
      by each scoring system. RESULTS: The mean age of the 97 patients was 7.1 +/- 5.2
      (1-17) years. The mean stone burden and number were 388.4 +/- 233.9 mm(2) and 1.5
      +/- 1.3, respectively. The mean procedure, fluoroscopy, and hospitalization times
      were 78.2 +/- 32.8 minutes, 144.8 +/- 84.3 seconds, and 4.1 +/- 2.8 days,
      respectively. The mean hematocrit drop was calculated as 2.2 +/- 2.2. The mean
      scores were 1.7 +/- 1.0 and 259.9 +/- 50.6 for Guy's and CROES scoring systems,
      respectively. In the multivariate analysis, stone-free status was found to be
      associated with Guy's (r: -0.464, p: .000) and CROES (r: 0.490, : 0.000) scoring
      systems and stone burden (r: -0.161, p: .041). In the analysis of factors related
      to complication, Guy's score was identified as an independent predictor of
      complication (p: .02, odds ratio: 1.9, 95% confidence interval 1.097-3.319).
      CONCLUSION: According to our results, using Guy's and CROES scoring systems,
      stone-free ratios after percutaneous nephrolithotomy may be predicted
      preoperatively. In addition, Guy's system is a predictor of postoperative
      complication rate.

PMID- 27045709
TI  - Building the Case for Adjuvant Chemotherapy After Radical Cystectomy: Commentary
      on: Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer.

PMID- 27045710
TI  - Robotic-assisted Laparoscopic Radical Prostatectomy From a Single Chinese Center:
      A Learning Curve Analysis.
AB  - OBJECTIVE: To investigate the learning curve of robotic-assisted laparoscopic
      radical prostatectomy (RALP) and analyze whether a surgeon's prior surgical
      experience has effects on the surgery. PATIENTS AND METHODS: From April 2012 to
      August 2015, 3 surgeons performed RALP on 355 consecutive patients with prostate
      cancer. Among these cases, 184 were by surgeon A with prior open experiences, 92
      by surgeon B with both open and laparoscopic experiences, and 79 by surgeon C
      with laparoscopic experiences only. Perioperative, oncological, and functional
      outcomes were evaluated and compared between surgeons. Learning curve patterns
      were evaluated to determine the number of cases to reach plateau. RESULTS: Marked
      difference was observed in operative time among the 3 groups (all P <.05). Length
      of hospital stay was also statistically significant (all P <.001), except for
      that between Group B and Group C (P = .739). Continence at 1-year and 6-month
      postoperatively was better in Groups B and C compared with Group A (P <.001).
      Intraoperative blood loss, pathologic stage, positive surgical margin,
      biochemical recurrence-free rate, and other pathological findings showed no
      statistical significance between the groups. The number of cases required to
      reach plateau may vary for surgeons with different surgical experiences.
      CONCLUSION: Different early surgical background may affect the perioperative
      parameters of novice RALP surgeons. Previous laparoscopic experiences may provide
      additional advantage in learning curve parameters compared with surgeons with
      open experiences only. A better overall continence for laparoscopic surgeons
      requires further validation.

PMID- 27045711
TI  - Prostate Biopsy Complications: A Dual Analysis.
AB  - OBJECTIVE: To measure prostate needle biopsy (PNB)-associated complications and
      place of treatment: inpatient hospitalization and outpatient treatment. An
      electronic medical record (EMR) data query is compared to a patient questionnaire
      survey. MATERIALS AND METHODS: A total of 2410 patients underwent 2588 biopsies
      and were evaluated for PNB-associated complications. Two approaches were used:
      (1) EMR analysis based on International Classification of Diseases, Ninth
      Revision, and Current Procedural Terminology coding and chart review; and (2)
      patient-reported questionnaire and chart review validation. Serious complications
      were defined as any complication leading to a related hospitalization, visit to
      the emergency department (ED), urgent care (UC), or doctor's office within 30
      days of the biopsy. RESULTS: The EMR study revealed 69 (2.67%) serious
      complications leading to either hospitalization or treatment at an ED, UC, or
      doctor's office. Thirty serious complications led to hospitalization (1.16%), 14
      patients (0.54%) were treated at the ED, 1 was managed at a UC (0.04%), and 24
      (0.93%) were treated at the doctor's office. Of the 847 (35.1%) questionnaires
      considered appropriate for analysis, 36 (4.25%) reported treatment in either the
      hospital, ED, UC, or doctor's office. Nine patients (1.06%) reported being
      hospitalized within 30 days of the procedure, whereas 27 patients (3.19%) were
      treated in an outpatient setting, 8 (0.94%) at the ED, 3 (0.35%) at a UC, and 16
      (1.89%) at the doctor's office. CONCLUSION: Our dual analysis study indicates a
      slightly greater than 1% incidence of hospitalization due to serious
      complications following PNB. Serious complications appear to be more frequently
      managed outside the hospital setting (ED, UC, and doctor's office).

PMID- 27045712
TI  - Comparison of blast-exposed OEF/OIF veterans with and without a history of TBI
      symptoms on a brief computerized neuropsychological battery.
AB  - Mild traumatic brain injuries (mild TBIs) resulting from exposure to Improvised
      Explosive Devices (IEDs) are highly prevalent among veterans of the wars in Iraq
      and Afghanistan. This exploratory study compared the neurocognitive performance
      of blast-exposed veterans with (n = 19) and without (n = 15) reported symptoms of
      mild TBI. All subjects had diagnoses of posttraumatic stress disorder (PTSD).
      Neurocognitive testing was administered using a well-established computerized
      battery, the Penn Computerized Neuropsychological Battery (CNB), and groups were
      well matched on age, race, education, and time since most recent blast exposure.
      Although differences were not observed on CNB accuracy scores, MANOVAs revealed
      slower processing speed in the mTBI group when answering correctly on tests of
      simple and sustained attention, with large effect sizes. Results suggest a
      potential speed-accuracy tradeoff in blast-related mild TBI, which should be
      further examined in larger samples.

PMID- 27045713
TI  - Deciphering and shaping bacterial diversity through CRISPR.
AB  - Phage and bacteria have engaged in a sustainable arms race, a seemingly endless
      conflict, since the beginning of time. CRISPR-Cas systems shape and generate
      environmental diversity through evolution of both predator and prey genomes.
      Indeed, the gain or loss of CRISPR-mediated immunity and genome maintenance can
      spark speciation in bacteria. Alternatively, turning CRISPR-Cas on the host by
      targeting chromosomal DNA has led to the development of next-generation smart
      antimicrobials and genetic screening and engineering technologies. Although the
      ability to target and cleave DNA in a sequence-specific manner is a powerful
      mechanism utilized by bacteria to fend off phage, plasmids, and potentially
      harmful nucleic acids, it is also a promising technology for programmable
      targeting of undesirable bacteria in microbiome consortia.

PMID- 27045714
TI  - A Randomized Controlled Trial to Evaluate if Computerized Cognitive
      Rehabilitation Improves Neurocognition in Ugandan Children with HIV.
AB  - OBJECTIVES: Clinically stable children with HIV can have neuromotor, attention,
      memory, visual-spatial, and executive function impairments. We evaluated
      neuropsychological and behavioral benefits of computerized cognitive
      rehabilitation training (CCRT) in Ugandan HIV children. DESIGN: One hundred fifty
      nine rural Ugandan children with WHO Stage I or II HIV disease (6 to 12 years; 77
      boys, 82 girls; M = 8.9, SD = 1.86 years) were randomized to one of three
      treatment arms over a 2-month period. METHODS: The CCRT arm received 24 one-hour
      sessions over 2 months, using Captain's Log (BrainTrain Corporation) programmed
      for games targeting working memory, attention, and visual-spatial analysis. These
      games progressed in difficulty as the child's performance improved. The second
      arm was a "limited CCRT" with the same games rotated randomly from simple to
      moderate levels of training. The third arm was a passive control group receiving
      no training. All children were assessed at enrollment, 2 months (immediately
      following CCRT), and 3 months after CCRT completion. RESULTS: The CCRT group had
      significantly greater gains through 3 months of follow-up compared to passive
      controls on overall Kaufman Assessment Battery for Children-second edition (KABC
      II) mental processing index (p < .01), planning (p = .04), and knowledge (p =
      .03). The limited CCRT group performed better than controls on learning (p =
      .05). Both CCRT arms had significant improvements on CogState Groton maze
      learning (p < .01); although not on CogState attention/memory, TOVA/impulsivity,
      or behavior rating inventory for executive function and child behavior checklist
      (psychiatric behavior/symptom problems) ratings by caregiver. CONCLUSIONS: CCRT
      intervention can be effective for neurocognitive rehabilitation in children with
      HIV in low-resource settings, especially in children who are clinically stable on
      ARV treatment.

PMID- 27045716
TI  - [The key phase of development of laboratory medicine--establishing the system of
      clinical laboratory diagnosis report].

PMID- 27045715
TI  - Correction: Dehydroepiandrosterone Sulfate Stimulates Expression of Blood-Testis
      Barrier Proteins Claudin-3 and -5 and Tight Junction Formation via a Gnalpha11
      Coupled Receptor in Sertoli Cells.

PMID- 27045717
TI  - [New evidences of studies of zoledronic acid in breast cancer patients with bone
      metastases].

PMID- 27045718
TI  - [Relevance between TOP2A, EGFR gene expression and efficacy of docetaxel plus
      epirubicin as neoadjuvant chemotherapy in triple negative breast cancer
      patients].
AB  - OBJECTIVE: To retrospectively analyze the relevance between DNA topoisomerase II
      alpha (TOP2A), epidermal growth factor receptor (EGFR) gene expression and
      efficacy of docetaxel plus epirubicin as neoadjuvant chemotherapy in triple
      negative breast cancer (TNBC) patients. METHODS: A total of 53 women with triple
      negative breast cancer who underwent docetaxel plus epirubicin as neoadjuvant
      chemotherapy were included in this study. The gene detection was done in the
      samples before chemotherapy by DNA chip technology. The relevance between TOP2A,
      EGFR gene expression and efficacy, pathological complete response (pCR) rate of
      neoadjuvant chemotherapy were retrospectively analyzed. RESULTS: The high
      expression rate of TOP2A in all the TNBC patients was 35.8% (19/53), while the
      rate of EGFR was 39.6% (21/53). The overall pCR rate of TNBC patients who
      underwent docetaxel plus epirubicin as neoadjuvant chemotherapy was 18.9%
      (10/53). The pCR rate was 31.6% (6/19) in TNBC patients whose TOP2A expression
      was high, compared to 11.8% (4/34) in whose was low (P>0.05). The pCR rate was
      28.6% (6/21) in TNBC patients whose EGFR expression was high, compared to 12.5%
      (4/32) in whose was low (P>0.05). The pCR rate was 75.0% (6/8) in TNBC patients
      whose TOP2A, EGFR expression were both high, and was significantly higher than
      that in all the TNBC patients (P<0.01). CONCLUSIONS: Efficacy of docetaxel plus
      epirubicin as neoadjuvant chemotherapy in TNBC patients can be predicted by
      detecting TOP2A, EGFR gene expression. The result may contribute to the
      development of more individualized neoadjuvant chemotherapy.

PMID- 27045719
TI  - [Predictive value of deubiquitination enzymes USP37 in the prognosis of breast
      cancer].
AB  - OBJECTIVE: To explore the expression of Ubiquitin-specific processing enzyme
      37(USP 37)in breast cancer and its association with the prognosis of breast
      cancer. METHODS: In this study, the method of Western blot was utilized to
      examine the expression of USP37 protein in breast cancer fresh tissue.
      Immunohistochemistry (IHC) was used to determine the expression of USP37 in 533
      cases of breast cancer. Receive operating characteristic (ROC) curve analysis was
      employed to determine a cut-off score for USP37 expression. For validation, the
      ROC-derived cut-off score was subjected to analysis the association of USP37
      expression with cancer patient outcome and clinical characteristics. RESULTS:
      USP37 protein was mainly located in cytoplasm of the cell, occasionally in
      nucleus by immunohistochemistry. In the normal breast tissue, USP37 was not
      expressed or with low expression level, while in the 533 cases of breast cancer,
      the high USP37 expression was detected in 50.7% samples (270/533) with
      corresponding low or negative expression rate 49.3% (263/533). We found that
      USP37 was highly expressed in primary breast cancer tissues compared to paired
      adjacent non-cancerous tissues. High expression of USP37 was associated with
      breast cancer node classification, molecular classification and proliferation
      biomarker Ki67. Both univariate and multivariate analyses further revealed that
      USP37 expression was an independent poor prognostic parameter for overall
      survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS)
      in breast cancer. Furthermore, USP37 expressions divided the luminal and triple
      negative breast cancer into different prognosis subgroups. CONCLUSION: Our
      findings first provide evidences that high expression of USP37 served as an
      independent molecular biomarker for poor prognosis in breast cancer.

PMID- 27045720
TI  - [Expression of FAS-AS1 in breast cancer and its effect on the host gene sFas].
AB  - OBJECTIVE: To investigate the expression level of antisense transcript of FAS
      (FAS-antisense 1, FAS-AS1) in breast cancer, and its effect on the host gene
      soluble Fas receptor (sFas). METHODS: The expression of FAS-AS1 and sFas gene was
      detected in 20 cases of breast cancer tumors and breast cancer cells and their
      normal counterparts by using real-time quantitative polymerase chain reaction(RT
      qPCR). The effects of FAS-AS1 on the expression of sFas gene in breast cancer
      cells were analyzed by overexpressing FAS-AS1 in breast cancer cells. RESULTS:
      FAS-AS1 expression in breast cancer tissue and cell lines was significantly lower
      than that of adjacent breast tissue (P=0.000) and normal breast cells (P<0.01).
      However, sFasexpression in the breast cancer tissue and cell lines was
      significantly higher than that of adjacent breast tissue (P=0.001) and normal
      breast cells (P<0.01). The expression of FAS-AS1 was negatively correlated with
      the expression of sFas(r=-0.751, P=0.020). FAS-AS1 expression was observed to be
      closely correlated with tumor size (r(2)=0.351, P=0.025) and lymph node
      metastasis (r(2)=0.265, P=0.043). Expression of sFas and cell proliferation was
      significantly reduced in FAS-AS1-overexpressing MCF-7 cells (P<0.05). CONCLUSION:
      FAS-AS1 is distinctly downexpressed in breast cancer, and it has certain effects
      on the expression of host gene sFas and breast cancer development.

PMID- 27045721
TI  - [Expression of enterotoxigenic Bacteroides fragilis and polyketide synthase gene
      expressing Escherichia coli in colorectal adenoma patients].
AB  - OBJECTIVE: To investigate the distribution of various bacteria in adenoma tissue
      of colorectal adenoma (T/CRA), normal colonic mucosa tissue adjacent to the
      adenoma (N/CRA), and healthy colonic mucosa tissue (N/H) by comparing the number
      of total bacteria, Bacteroides fragilis (BF), enterotoxigenic Bacteroides
      fragilis (ETBF), polyketide synthase (pks) gene-expressing Escherichia
      coli(E.coli)(pks(+) E. coli)among the above 3 types of tissues. METHODS: A total
      of 36 patients diagnosed with colorectal adenoma by colonoscopy and pathology in
      Department of Gastroenterology, Peking University People's Hospital from
      September 2011 to September 2013 were selected into this study. T/CRA and N/CRA
      tissues from the 36 patients and N/H tissues from 18 healthy controls were
      collected for DNA extraction. The number of total bacteria, BF, ETBF, pks(+) E.
      coli was detected by quantitative real time PCR, and their correlation with
      colorectal adenoma was analyzed. RESULTS: (1) The number of total bacteria
      decreased gradually from N/H, N/CRA, to T/CRA, with the median values being
      3.18*10(8,) 1.57*10(8,) and 7.91*10(7) copies/g, respectively, and with
      significant difference among the three groups and between each two groups (all
      P<0.01). (2) The content of BF decreased gradually from N/H, N/CRA, to T/CRA, the
      median values being 6.03*10(5,) 4.28*10(4,) and 5.48*10(3) copies/g,
      respectively, and with significant difference among the three groups and between
      each two groups (all P<0.01). (3) The toxin content produced by ETBF increased
      from N/H, N/CRA, to T/CRA, the relative expression being 1.73+/-0.30, 6.15+/
      1.52, and 8.54+/-1.80, respectively. Significant difference was found between the
      T/CRA and N/H tissue (P=0.003), but not between any other two groups. (4) The
      expression of clbB in pks(+) E.coli was highest in T/CRA colonic tissue (2.96+/
      0.28), followed by the N/CRA (2.79+/-0.19) and N/H tissue (1.06+/-0.08).
      Significant difference was found between T/CRA and N/H tissues, as well as
      between N/CRA and N/H tissues (both P<0.001), but not between T/CRA and N/CRA
      tissues. CONCLUSIONS: The number of total bacteria is markedly reduced in the
      colonic mucosa of CRA patients compared to normal people, while the expressions
      of ETBF and pks(+) E.coli are significantly increased. Such changes in total
      bacterial, ETBF and pks(+) E.coli concentrations in colonic mucosa may be related
      to the tumorigenesis of colorectal adenoma.

PMID- 27045722
TI  - [Effects of artesunate on cigarette smoke-induced lung oxidative damage in mice
      and the expression of Nrf2 and the possible mechanism].
AB  - OBJECTIVE: To explore the effects of artesunate on cigarette smoke-induced lung
      oxidative damage in mice and the expression of Nuclear factor-E2-related factor 2
      (Nrf2). METHODS: In vivo: A total of 40 female specific pathogen free BALB/c mice
      were divided randomly into four groups: normal group, cigarette smoke group,
      vehicle group and artesunate group. The latter three groups were exposed on
      cigarette smoke for 40 days. Vehicle (5% NaHCO3 containing 5% dimethyl sulfoxide,
      0.1 ml of each mice) or artesunate (30 mg/kg, dissolved in the 0.1 ml vehicle)
      was given by intraperitoneal injections before each passive smoking of the
      vehicle or artesunate group. Saline of 0.1ml was given to the normal and
      cigarette smoke groups as negative controls. Cells in bronchoalveolar lavage
      fluid (BALF) were collected and analyzed by absolute different cell counts.
      Interleukin (IL)-8 levels in BALF and 3-nitrotyrosine (NT) levels in lung tissue
      were tested by emzyme linked immunosorbent assay (ELISA). Malondialdehyde levels
      in serum, total superoxide dismutase (SOD) activity and total glutathione
      peroxidase (GPx) activity in lung tissue were detected. The pathological changes
      of lung tissues were observed by HE staining. And the expression levels of Nrf2
      were measured by Westernblotting. In vitro: 16HBE cells were cultured and
      transfected with Nrf2 siRNA. Cigarette smoke extract (CSE) were used to stimulate
      the secretion of IL-8 in cells. Cells were divided into five groups: blank group,
      non-transfected non-artesunate group, non-transfected artesunate group,
      transfected non-artesunate group and transfected artesunate group. The latter
      four groups were incubated with CSE, and non-transfected artesunate and
      transfected artesunate groups were intervened with artesunate (30 MUmol/L) before
      CSE incubation. The IL-8 levels of each group were measured using ELISA kit.
      RESULTS: In vivo: The total cell counts of BALF in artesunate group were
      significantly lower than the vehicle group [21.00(2.50)*10(4)/ml vs
      35.50(2.50)*10(4)/ml, P<0.001], especially neutrophil counts [6.00(5.12)*10(4)/ml
      vs 13.60(5.25)*10(4)/ml, P<0.001]. The IL-8 levels in BALF, malondialdehyde
      levels in serum, 3-NT levels and total SOD activity in lung tissue of artesunate
      group were all drastically lower than those in the vehicle group [(508+/-55) vs
      (912+/-68) ng/L, (38.2+/-8.8) vs (48.7+/-10.6) MUmol/L, (28.5+/-5.8) vs (50.0+/
      9.7) MUg/L and (11.8+/-1.8) vs (18.0+/-5.3) U/mg protein, respectively, all
      P<0.05]. No significant difference of total GPx activity existed in these four
      groups. And the expression level of Nrf2 in artesunate group significantly
      increased than that in vehicle group (P=0.008). In vitro: The IL-8 level of the
      non-transfected artesunate group was significantly lower than the non-transfected
      non-artesunate group [(352+/-26) vs (765+/-22) ng/L, P<0.001], while the IL-8
      levels between the transfected artesunate and transfected non-artesunate groups
      had no significant difference. CONCLUSION: Arteunate attenuates cigarette smoke
      induced lung oxidative damage in mice and increases the expression level of Nrf2,
      and its effects might be mediated by the actions of nuclear Nrf2.

PMID- 27045723
TI  - [Inhibition of suppressor of cytokine signaling 1 on lipopolysaccharide-induced
      mucin5AC hypersecretion and the mechanism in human bronchial epithelial cells].
AB  - OBJECTIVE: To explore the inhibitory role of suppressor of cytokine signaling 1
      (SOCS1) in lipopolysaccharide (LPS)-induced mucin5AC (MUC5AC) hypersecretion and
      the potential mechanism involved in this process. METHODS: The human bronchial
      epithelial cells 16HBE were divided into 0, 0.5, 1, 6, 12 and 24 h groups
      according to the time of LPS challenge. In gain- and loss- of functions
      experiments, wild-type SOCS1 and SOCS1-targeted siRNA (SOCS1-siRNA) were
      synthesized to identify the function of SOCS1 in LPS-mediated MUC5AC
      hypersecretion, and named wild-type SOCS1 group and SOCS1-siRNA group,
      respectively, and the non-transfected group and non-targeted siRNA group were
      used as controls. In Filgotinib group, the specific inhibitor of Janus kinase 1
      (JAK1), Filgotinib, was used to detect the role of JAK1/signal transducer and
      activator of transcription 1 (STAT1) signaling pathway in LPS challenge, and the
      aqueous physiological buffer group was used as the control. The production of
      MUC5AC protein was measured by enzyme linked immunosorbent assay (ELISA), and the
      amount of MUC5AC protein was normalized to the total protein in cell lysates and
      was expressed as MUg/mg cell lysates. The proteins expressions of SOCS1,
      phosphorylation of JAK1 and STAT1 were measured by Western blot, and the total
      expression of its protein (for JAK1 and STAT1) or beta-actin (for SOCS1) was used
      as the loading control. RESULTS: Compared to 0 h group, LPS induced a robust
      induction in MUC5AC expression, the expression levels of MUC5AC in 0, 0.5, 1, 6,
      12 and 24 h groups were (2.86+/-0.20), (3.42+/-0.29), (3.43+/-0.12), (10.22+/
      0.96), (14.56+/-1.12), (14.15+/-1.34) MUg/mg, in association with a decrease of
      SOCS1 expression. And in 6 h group, the expressions of MUC5AC and SOCS1 were both
      medium up-regulated (all P<0.05). Consequently, the application of LPS for 6 h
      was selected as the optimal responses period in the ensuing experiments. Compared
      to the expression of MUC5AC protein in non-transfected group, high level of SOCS1
      in wild-type SOCS1 group led to a reduced phosphorylation of JAK1/STAT1, as well
      as Filgotinib did, thereby suppressing excessive MUC5AC production in wild-type
      SOCS1 group and Filgotinib group [(4.04+/-0.65), (7.02+/-0.83) vs (10.37+/-1.00)
      MUg/mg] (all P<0.05). Conversely, compared to the expression of MUC5AC in non
      targeted siRNA group, down-regulation of SOCS1 in SOCS1-siRNA group promoted the
      phosphorylation of JAK1/STAT1, and then further increased MUC5AC production
      [(13.69+/-1.32) vs (11.01+/-1.41) MUg/mg] (all P<0.05). CONCLUSION: These results
      show that SOCS1 suppresses LPS-promoted MUC5AC hypersecretion through the
      inhibition of JAK1/STAT1 signaling pathway.

PMID- 27045724
TI  - [Study on culture, identification and differentiation of primary rat skeletal
      muscle satellite cells].
AB  - OBJECTIVE: To establish the isolation, culture and identification methods of
      primary rat skeletal muscle satellite cells (SMSC) and observe its
      characterization of differentiation in vitro. METHODS: Skeletal muscle satellite
      cells were obtained by tissue block culture method in combination with pre
      plating techniques, and the purity of these cells was detected by both
      immunocytochemistry and fluorescence activated cell sorter (FACS) with Pax7 as
      marker of SMSC. Myogenesis of these cells was induced in differentiation medium
      and the mRNA expressions of myogenic differentiation gene (MyoD) and Myogenin
      were determined by Real-time polymerase chain reaction (PCR). RESULTS: Cells
      crawled out from the edge of tissue blocks after 1 week of culture. After
      purification by pre-plating techniques, more than 97.6% of the cells expressed
      Pax7, a unique marker of satellite cells. The mRNA of MyoD and Myogenin showed
      time-specific expression in the myogenesis induction process in vitro.
      CONCLUSION: Skeletal muscle satellite cells with high purity and strong
      differentiation ability can be obtained by means of tissue block culture method.

PMID- 27045725
TI  - [Effects of resuscitation by different formulation on oxygen metabolism during
      shock stage of burn injury in swine].
AB  - OBJECTIVE: To explore the effects of different fluid resuscitation regimens on
      oxygen metabolism during shock stage of burn injury in swine. METHODS: Twelve
      Bama miniature swines were divided into crystal and colloid group (Group 1) and
      Parkland group (Group 2) according to the random number table. The swine models
      of burns shock were established. The fluid resuscitation was begun at post injury
      hour (PIH) 2 according to Chinese formulation or Parkland's formulation,
      respectively. The blood pressure, urine volume, heart rate, central venous
      pressure (CVP), pulmonary capillary wedge pressure (PCWP) were recorded. The
      liquid volume was calculated at the first and second PIH 24. The changes in
      oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction (O2Ext) and D
      lactate (D-LA) were determined before injury and at PIH 4, 8, 24, and 48.
      Statistical analyses were performed. RESULTS: There were no statistical
      differences between the two groups in blood pressure, urine volume, heart rate,
      CVP, PCWP in every interval (all P>0.05). The resuscitation liquid volume in the
      two groups during the first and second PIH 24 conformed to the domestic
      consensus. The VO2 at PIH 8 was significantly higher than that of pre-burn in
      both groups [(190+/-29) vs (83+/-42) L.min(-1).m(-2,) (149+/-33) vs (85+/-15)
      L.min(-1).m(-2,) both P<0.05], and the VO2 at PIH 8 was significantly higher in
      Group 1 than that in Group 2 (P<0.05). The DO2 at PIH 24 in Group 1 was
      significantly lower than that in Group 2 [(686+/-72) vs (853+/-81) L.min(-1).m(
      2,) P<0.05]. There were no significant differences between the two groups in
      O2Ext at any time points (all P>0.05). The D-LA at PIH 8 was significantly higher
      in Group 1 than that in Group 2 [(53+/-4) vs (45+/-6) mmol/L, P<0.05].
      CONCLUSION: There are no significant differences in the resuscitation effects of
      the crystal and colloid resuscitation regimen and Parkland's formulation on
      oxygen metabolism during shock stage of burn injury in swine.

PMID- 27045726
TI  - Hidden Hypercalcemia and Mortality Risk in Incident Hemodialysis Patients.
AB  - CONTEXT: Neither uncorrected- nor albumin-corrected total calcium reliably
      predict ionized calcium in patients with end-stage renal disease. However, little
      is known about the consequences of inaccurate assessment of calcium concentration
      using total calcium. OBJECTIVE: We hypothesized that hidden hypercalcemia (ie,
      elevated ionized calcium with normal total calcium) and apparent hypercalcemia
      (ie, elevated ionized calcium with elevated total calcium) are both associated
      with increased mortality risk. DESIGN, SETTING, AND PATIENTS: We identified 874
      incident hemodialysis patients with measured serum ionized calcium, total
      calcium, albumin, phosphorus, and bicarbonate from October 2007 to December 2011,
      using data from a large dialysis organization in the United States. EXPOSURES:
      Serum concentrations of ionized calcium and total calcium were measured. MAIN
      OUTCOME MEASURE: The primary outcome was all-cause mortality. RESULTS: There was
      only fair interindex agreement with calcium status between ionized calcium and
      uncorrected or corrected total calcium (kappa = 0.32 and 0.27, respectively).
      Among patients with high ionized calcium (>1.32 mmol/liter), 88% and 70% patients
      were incorrectly categorized as being normocalcemic using uncorrected and
      corrected total calcium, respectively, and were thus considered to have "hidden
      hypercalcemia." Compared to patients with low-normal ionized calcium (1.16-1.24
      mmol/liter), patients with high ionized calcium had a significantly higher
      mortality risk (adjusted hazard ratio, 1.77; 95% confidence interval, 1.13-2.75).
      Furthermore, compared to patients with normocalcemia (ionized calcium 1.16-1.32
      mmol/liter), those with hidden hypercalcemia by uncorrected and corrected total
      calcium also had a higher risk for death (adjusted hazard ratio 1.75 [95%
      confidence interval 1.11-2.75] and 1.80 [95% confidence interval, 1.11-2.90],
      respectively). CONCLUSION: The majority of end-stage renal disease patients with
      elevated ionized calcium are incorrectly categorized as normocalcemic using
      conventional total calcium measurements; these patients have a higher death risk.
      Future research is needed to establish whether reducing ionized calcium
      concentrations in these patients improves clinical outcomes.

PMID- 27045727
TI  - Predictors of Positive Treatment Outcome in People With Anorexia Nervosa Treated
      in a Specialized Inpatient Unit: The Role of Early Response to Treatment.
AB  - OBJECTIVE: To investigate factors which predict positive treatment outcome in
      inpatients with anorexia nervosa (AN), particularly the role of early treatment
      response. METHOD: 102 patients entering specialist inpatient treatment were
      assessed for eating disorder history, psychopathology, and motivation to change.
      Predictive factors assessed were: early treatment response defined as weight
      increase of at least 0.5-1 kg/week during the first 6 weeks of treatment (n=87),
      admission body mass index (BMI), onset age, chronicity, motivation to change,
      diagnosis, and previous hospitalization for AN. Positive treatment outcome was
      defined as achieving a BMI of 17.5 kg/m(2) within an individual time frame.
      RESULTS: Logistic regression indicated that patients were 18 times more likely to
      reach positive treatment outcome if they met the National Institute for Health
      and Care Excellence weight guidelines within the first 6 weeks of
      hospitalization. Higher admission BMI was also found to predict positive
      treatment outcome. DISCUSSION: Higher entry BMI and early weight gain predict
      positive treatment outcome in individuals receiving specialist AN inpatient
      treatment. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders
      Association.

PMID- 27045728
TI  - Factors associated with ADL/IADL disability in community dwelling older adults in
      the Irish longitudinal study on ageing (TILDA).
AB  - PURPOSE: To identify the factors associated with disability across many domains
      using a large powered sample in the activities of daily living (ADL) and
      instrumental activities of daily living (IADL). METHODS: Those aged >=65 years
      from the Irish longitudinal study on ageing (TILDA) were included in this cross
      sectional analysis. Three logistic regression models were used to examine the
      relationships between 25 health, psychological and sociodemographic variables and
      difficulties in ADL, IADL and ADL/IADL combined. RESULTS: The proportion of those
      reporting combined ADL/IADL difficulties was 18%. More individuals reported
      difficulty with ADLs (13%) than IADLS (11%). The main model showed that after
      age, the top three factors associated with difficulty in ADL/IADL combined were
      pain, taking five or more medications and depression. After age, the factors with
      the highest impact on ADL disability were pain, taking five or more medications
      and body mass index (BMI); the factors with the highest impact on IADL were being
      separated or divorced, living with others (non-spouse) and self-rated memory.
      CONCLUSIONS: Awareness of sociodemographics and early interventions for pain and
      cognitive deficits could reduce ADL/IADL disability and promote successful
      ageing. Identification of variables that influence ADL/IADLs can be used to
      inform policy and practice. Implications for rehabilitation After age, pain and
      taking five or more medications were the strongest factors associated with
      difficulty in ADL/IADL combined and ADL alone. Practice therefore needs to be
      cognizant that it is not the disease label but the symptoms of a disease that
      affect ADL and IADL activities. Given the strong influence of pain on
      difficulties with ADL and IADL, there is a need for early interventions from a
      multidisciplinary perspective for pain reduction, control, and self-management.
      These interventions should include development of pain-coping strategies and
      exercises to maintain mobility. After age, being separated/divorced or living
      with non-spouse others are the strongest factors associated with IADL
      difficulties. Awareness of these social factors can be used to inform support
      mechanisms, such as development of community services and suitable housing for
      those with these changing sociodemographics. Unsurprisingly, cognitive
      impairments were strongly associated with IADL difficulties. Simple cognitive
      screening assessments could be used for early detection of cognitive changes. In
      order to maintain optimal cognitive functioning, rehabilitation professionals
      should facilitate older adults' engagement in activities that are cognitively
      demanding and socially interactive.

PMID- 27045729
TI  - Measurement of the Hydrophobic Force in a Soft Matter System.
AB  - The hydrophobic attraction describes the well-known tendency for nonpolar
      molecules and surfaces to agglomerate in water, controlled by the reorganization
      of intervening water molecules to minimize disruption to their hydrogen bonding
      network. Measurements of the attraction between chemically hydrophobised solid
      surfaces have reported ranges varying from tens to hundreds of nanometers, all
      attributed to hydrophobic forces. Here, by studying the interaction between two
      hydrophobic oil drops in water under well-controlled conditions where all known
      surface forces are suppressed, we observe only a strong, short-ranged attraction
      with an exponential decay length of 0.30 +/- 0.03 nm-comparable to molecular
      correlations of water molecules. This attraction is implicated in a range of
      fundamental phenomena from self-assembled monolayer formation to the action of
      membrane proteins and nonstick surface coatings. 

PMID- 27045730
TI  - A genetic risk score is associated with statin-induced low-density lipoprotein
      cholesterol lowering.
AB  - AIM: To find new genetic loci associated with statin response, and to investigate
      the association of a genetic risk score (GRS) with this outcome. PATIENTS &
      METHODS: In a discovery meta-analysis (five studies, 1991 individuals), we
      investigated the effects of approximately 50000 single nucleotide polymorphisms
      on statin response, following up associations with p < 1 * 10(-4) (three
      independent studies, 5314 individuals). We further assessed the effect of a GRS
      based on SNPs in ABCG2, LPA and APOE. RESULTS: No new SNPs were found associated
      with statin response. The GRS was associated with reduced statin response: 0.0394
      mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 * 10(-4)). CONCLUSION: The GRS
      was associated with statin response, but the small effect size (~2% of the
      average low-density lipoprotein cholesterol reduction) limits applicability.

PMID- 27045731
TI  - Cdk1 activity acts as a quantitative platform for coordinating cell cycle
      progression with periodic transcription.
AB  - Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires
      the periodic expression of particular gene clusters in different cell cycle
      phases. However, the interplay between the networks that generate these
      transcriptional oscillations and the core cell cycle machinery remains largely
      unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate
      that periodic expression is governed by quantitative changes in Cdk1 activity,
      with different clusters directly responding to specific activity levels. We
      further establish that cell cycle events neither participate in nor interfere
      with the Cdk1-driven transcriptional program, provided that cells are exposed to
      the appropriate Cdk1 activities. These findings contrast with current models that
      propose self-sustained and Cdk1-independent transcriptional oscillations. Our
      work therefore supports a model in which Cdk1 activity serves as a quantitative
      platform for coordinating cell cycle transitions with the expression of critical
      genes to bring about proper cell cycle progression. 

PMID- 27045732
TI  - Nanowire-templated formation of SnO2/carbon nanotubes with enhanced lithium
      storage properties.
AB  - In this work, we have designed and synthesized SnO2 nanotubes wrapped by a porous
      carbon layer via a multistep method. Single-crystalline MnO(x) nanowires are
      employed as the template. SnO2 is grown on MnO(x) nanowires by a simple
      hydrothermal method to generate MnO(x)/SnO2 core-shell nanocables, followed by
      further coating with a layer of polydopamine. After carbonization of polydopamine
      and selective removal of MnO(x) nanowires, carbon coated SnO2 nanotubes are
      obtained. This structure combines several advantages. First, the internal empty
      space of the tubular structure can buffer the huge volume variation during
      lithium insertion-extraction processes properly, leading to improved cycling
      performance. Second, the nanosized SnO2 subunits and porous carbon coating not
      only shorten the distance for lithium ion diffusion but also offer large
      electrode-electrolyte contact area for fast Li(+) crossing the interface, thus
      enabling improved rate capability. Third, the flexible carbon coating is closely
      covered onto the SnO2 nanocrystals, which could facilitate the electronic
      transport and also significantly mitigate the pulverization. As a result, the as
      synthesized SnO2/C-NT nanocomposites exhibit a high reversible capacity of 596 mA
      h g(-1) after 200 cycles, as well as an outstanding rate capability.

PMID- 27045733
TI  - Controlling superconducting spin flow with spin-flip immunity using a single
      homogeneous ferromagnet.
AB  - Spin transport via electrons is typically plagued by Joule heating and short
      decay lengths due to spin-flip scattering. It is known that dissipationless spin
      currents can arise when using conventional superconducting contacts, yet this has
      only been experimentally demonstrated when using intricate magnetically
      inhomogeneous multilayers, or in extreme cases such as half-metals with
      interfacial magnetic disorder. Moreover, it is unknown how such spin
      supercurrents decay in the presence of spin-flip scattering. Here, we present a
      method for generating a spin supercurrent by using only a single homogeneous
      magnetic element. Remarkably, the spin supercurrent generated in this way does
      not decay spatially, in stark contrast to normal spin currents that remain
      polarized only up to the spin relaxation length. We also expose the existence of
      a superconductivity-mediated torque even without magnetic inhomogeneities,
      showing that the different components of the spin supercurrent polarization
      respond fundamentally differently to a change in the superconducting phase
      difference. This establishes a mechanism for tuning dissipationless spin and
      charge flow separately, and confirms the advantage that superconductors can offer
      in spintronics. 

PMID- 27045734
TI  - Death and the Oldest Old: Attitudes and Preferences for End-of-Life Care-
      Qualitative Research within a Population-Based Cohort Study.
AB  - INTRODUCTION: Increasing longevity means more people will be dying in very old
      age, but little is known about the preferences of the 'oldest old' regarding
      their care at the end of life. AIMS: To understand very old people's preferences
      regarding care towards the end of life and attitudes towards dying, to inform
      policy and practice. METHODS: Qualitative data collection for n = 42 population
      based cohort study participants aged 95-101 (88% women, 42% in long-term-care):
      topic-guided interviews with n = 33 participants and n = 39 proxy informants,
      most with both (n = 30: 4 jointly + separate interviews for 26 dyads). RESULTS:
      Death was a part of life: these very old people mainly live day-to-day. Most were
      ready to die, reflecting their concerns regarding quality of life, being a
      nuisance, having nothing to live for and having lived long enough. Contrasting
      views were rare exceptions but voiced firmly. Most were not worried about death
      itself, but concerned more about the dying process and impacts on those left
      behind; a peaceful and pain-free death was a common ideal. Attitudes ranged from
      not wanting to think about death, through accepting its inevitable approach to
      longing for its release. Preferring to be made comfortable rather than have life
      saving treatment if seriously ill, and wishing to avoid hospital, were commonly
      expressed views. There was little or no future planning, some consciously
      choosing not to. Uncertainty hampered end-of-life planning even when death was
      expected soon. Some stressed circumstances, such as severe dependency and others'
      likely decision-making roles, would influence choices. Carers found these issues
      harder to raise but felt they would know their older relatives' preferences,
      usually palliative care, although we found two discrepant views. CONCLUSIONS:
      This study's rare data show >=95-year-olds are willing to discuss dying and end
      of-life care but seldom do. Formal documentation of wishes is extremely rare and
      may not be welcome. Although being "ready to die" and preferring a palliative
      approach predominated, these preferences cannot be assumed.

PMID- 27045735
TI  - Physical activity in relation to urban environments in 14 cities worldwide: a
      cross-sectional study.
AB  - BACKGROUND: Physical inactivity is a global pandemic responsible for over 5
      million deaths annually through its effects on multiple non-communicable
      diseases. We aimed to document how objectively measured attributes of the urban
      environment are related to objectively measured physical activity, in an
      international sample of adults. METHODS: We based our analyses on the
      International Physical activity and Environment Network (IPEN) adult study, which
      was a coordinated, international, cross-sectional study. Participants were
      sampled from neighbourhoods with varied levels of walkability and socioeconomic
      status. The present analyses of data from the IPEN adult study included 6822
      adults aged 18-66 years from 14 cities in ten countries on five continents.
      Indicators of walkability, public transport access, and park access were assessed
      in 1.0 km and 0.5 km street network buffers around each participant's residential
      address with geographic information systems. Mean daily minutes of moderate-to
      vigorous-intensity physical activity were measured with 4-7 days of accelerometer
      monitoring. Associations between environmental attributes and physical activity
      were estimated using generalised additive mixed models with gamma variance and
      logarithmic link functions. RESULTS: Four of six environmental attributes were
      significantly, positively, and linearly related to physical activity in the
      single variable models: net residential density (exp[b] 1.006 [95% CI 1.003
      1.009]; p=0.001), intersection density (1.069 [1.011-1.130]; p=0.019), public
      transport density (1.037 [1.018-1.056]; p=0.0007), and number of parks (1.146
      [1.033-1.272]; p=0.010). Mixed land use and distance to nearest public transport
      point were not related to physical activity. The difference in physical activity
      between participants living in the most and least activity-friendly
      neighbourhoods ranged from 68 min/week to 89 min/week, which represents 45-59% of
      the 150 min/week recommended by guidelines. INTERPRETATION: Design of urban
      environments has the potential to contribute substantially to physical activity.
      Similarity of findings across cities suggests the promise of engaging urban
      planning, transportation, and parks sectors in efforts to reduce the health
      burden of the global physical inactivity pandemic. FUNDING: Funding for
      coordination of the IPEN adult study, including the present analysis, was
      provided by the National Cancer Institute of National Institutes of Health
      (CA127296) with studies in each country funded by different sources.

PMID- 27045736
TI  - Our health is a function of where we live.

PMID- 27045737
TI  - Perspectives About Family Meals from Racially/Ethnically and Socioeconomically
      Diverse Households With and Without an Overweight/Obese Child.
AB  - BACKGROUND: Several quantitative studies have found a protective association
      between family meal frequency and child and adolescent weight and weight-related
      behaviors (e.g., healthy dietary intake, less disordered eating behaviors).
      However, limited qualitative research has been conducted to understand more in
      depth about family meal-level characteristics (e.g., rules, responsibilities, and
      interpersonal dynamics) that may be risk or protective factors for child weight
      and weight-related behaviors. The current study aimed to identify family meal
      level characteristics within racially/ethnically and socioeconomically diverse
      households that were similar and/or different between households with and without
      an overweight/obese child. METHODS: The current study is a qualitative study
      including 118 parents of children ages 6-12 who participated in the Family Meals,
      LIVE! STUDY: Parents (92% female) were from racially/ethnically (87% minority)
      and socioeconomically (73% <$35,000 per year) diverse households. Parents were
      individually interviewed during a home visit. Data were stratified by child
      weight status (i.e., normal weight vs. overweight/obese) and analyzed using
      deductive and inductive content analysis. RESULTS: Qualitative results showed
      some similarities and some differences in family meal-level characteristics by
      child weight status that may provide insight into past research showing
      significant associations between family meal frequency and child weight and
      weight-related behaviors. Similar themes between families with and without an
      overweight/obese child included: family meals provide more healthful food; rules
      about manners; meal planning; and involving children in meal preparation. Themes
      that were different between families with and without an overweight/obese child
      included: connection and communication; "clean your plate rule"; electronic
      devices; and child behavior problems. CONCLUSIONS: Findings from the current
      study may be useful for developing interventions for racially/ethnically and
      socioeconomically diverse households with and without an overweight/obese child
      to be delivered through family meals.

PMID- 27045738
TI  - Localisation and protein-protein interactions of the Helicobacter pylori taxis
      sensor TlpD and their connection to metabolic functions.
AB  - The Helicobacter pylori energy sensor TlpD determines tactic behaviour under low
      energy conditions and is important in vivo. We explored protein-protein
      interactions of TlpD and their impact on TlpD localisation and function. Pull
      down of tagged TlpD identified protein interaction partners of TlpD, which
      included the chemotaxis histidine kinase CheAY2, the central metabolic enzyme
      aconitase (AcnB) and the detoxifying enzyme catalase (KatA). We confirmed that
      KatA and AcnB physically interact with TlpD. While the TlpD-dependent behavioural
      response appeared not influenced in the interactor mutants katA and acnB in
      steady-state behavioural assays, acetone carboxylase subunit (acxC) mutant
      behaviour was altered. TlpD was localised in a bipolar subcellular pattern in
      media of high energy. We observed a significant change in TlpD localisation
      towards the cell body in cheAY2-, catalase- or aconitase-deficient bacteria or in
      bacteria incubated under low energy conditions, including oxidative stress or
      respiratory inhibition. Inactivation of tlpD resulted in an increased sensitivity
      to iron limitation and oxidative stress and influenced the H. pylori
      transcriptome. Oxidative stress, iron limitation and overexpressing the iron
      sulfur repair system nifSU altered TlpD-dependent behaviour. We propose that TlpD
      localisation is instructed by metabolic activity and protein interactions, and
      its sensory activity is linked to iron-sulfur cluster integrity. 

PMID- 27045739
TI  - The effects of health counseling and exercise training on self-rated health and
      well-being in middle-aged men: a randomized trial.
AB  - BACKGROUND: Few community-based lifestyle interventions have examined subjective
      well-being. We examined the effects of health counseling and exercise training on
      self-rated health (SRH), self-rated well-being (SRW) and depressive symptoms in
      middle-aged men at increased risk for cardiovascular disease (CVD) in a
      randomized controlled trial. METHODS: Men (N.=168) with at least two CVD risk
      factors engaging in leisure-time physical activity less than three times/week
      were randomized into: A) a group receiving single-session health counseling; B) a
      group receiving single-session health counseling and three months of weekly
      structured group exercise training; or C) a control group. We assessed SRH and
      SRW using visual analogue scales and depressive symptoms using a brief depression
      screener (the Patient Health Questionnaire-2, PHQ-2). RESULTS: Generalized
      estimating equation (GEE) models showed that, after 3 and 12 months, SRH
      (P=0.024) and SRW (P=0.014) improved across all groups. We found no differences
      between the groups (group by time effect, P=0.44 and P=0.80). The proportion of
      men with PHQ-2 scores >=3 (positive depression screen) decreased in groups A
      (from 27% to 13%) and B (from 34% to 18%), but increased among controls (from 26%
      to 31%) (group by time effect, P=0.078). CONCLUSIONS: We found improvements in
      SRH and SRW, with a diminishing proportion of men screening positive for
      depression one year after a single health counseling session and a three-month
      exercise-training program. We detected, however, no statistically significant
      differences when comparing men who received health counseling or health
      counseling combined with exercise training to controls.

PMID- 27045740
TI  - Lifelong amateur endurance practice attenuates oxidative stress and prevents
      muscle wasting in senior adults.
AB  - BACKGROUND: The aim of the study was to investigate oxidative stress, muscle
      damage, enzymatic antioxidant defense and body composition in senior adults who
      have performed different lifelong physical activity practices. METHODS: Twenty
      three healthy senior men (60+/-1.88 years old) were divided into three groups
      according to their lifelong physical activity practice as follows: A) sedentary
      (N.=7); B) recreational (N.=9); and C) amateur (N.=7). Blood sampling was
      performed at rest to analyze plasma malondialdehyde (MDA) by TBARs-assay, nuclear
      DNA-damage in peripheral lymphocytes using Comet-Assay, the plasma enzymatic
      activity of glutathione peroxidase by spectrophotometry and serum alpha-actin
      release as skeletal muscle damage marker through western blot. Body composition
      was evaluated using anthropometric assessments by the ISAK protocol through
      skinfold thickness. RESULTS: The lowest value of MDA was shown in the amateur
      group. Nuclear DNA-damage was significantly lower in the recreational group than
      in sedentary and amateur groups (MD=5.53+/-1.70; P=0.013. MD=5.61+/-1.62;
      P=0.008), respectively. The amateur group showed trends toward higher glutathione
      peroxidase enzymatic activity than recreational and sedentary groups. Alpha-actin
      levels were significantly higher in the amateur compared with recreational
      (MD=4.34+/-0.46; P<0.001) and sedentary groups (MD=4.89+/-0.46; P<0.001). The
      sedentary group showed significantly lower muscle mass (MD=3.67+/-1.10; P=0.011)
      and higher fat mass (MD=4.19+/-0.98; P=0.001) than amateur group. CONCLUSIONS:
      The results described above suggest that the lifelong amateur endurance practice
      seems to improve oxidative stress response and strengthens hypertrophy mechanisms
      that might preserve muscle mass in senior adults.

PMID- 27045741
TI  - Is muscular strength balance influenced by menstrual cycle in female soccer
      players?
AB  - BACKGROUND: Muscular strength imbalance is an important risk factor for ACL
      injury, but it is not clear the impact of menstrual cycle on muscular strength
      balance. Our aims were to compare muscular balance (hamstring-to-quadriceps peak
      torque strength balance ratio) between luteal and follicular phases and compare
      gender differences relative to strength balance to observe possible fluctuations
      in strength balance ratio. METHODS: Thirty-eight soccer athletes (26 women and 12
      men) took part in this study. Athletes participated in two identical isokinetic
      strength evaluations for both knee (non-dominant [ND] and dominant [D]). Peak
      torque for quadriceps and hamstring muscles were measured in concentric mode and
      hamstring-to-quadriceps peak torque strength balance ratio calculated. RESULTS:
      Women had significantly lower hamstring-to-quadriceps peak torque strength
      balance ratio during the follicular compared to luteal phase, for the ND limb
      (P=0.011). However, no differences, between luteal and follicular phases, were
      observed in the D limb. In men, no difference in strength balance ratios was
      found between the ND and D limbs. CONCLUSIONS: These data may be useful in
      prevention programs for knee (ACL) injuries among soccer female athletes.

PMID- 27045742
TI  - Effect of gender specific anthropometric characteristics on lung function in
      young competitive triathletes from Malaysia.
AB  - BACKGROUND: Anthropometric and lung function characteristics of triathletes are
      important for the implementation of individual specific training and recovery
      recommendations. However, limited data are available for these parameters in
      triathletes. Hence, the aim of this study was to characterize and examine the
      gender differences of lung function and anthropometry parameters in competitive
      triathletes from Malaysia. METHODS: Body composition assessment and lung function
      tests were performed on sixteen competitive triathletes (nine male and seven
      female). The subject's body composition profile including muscle mass (kg), fat
      free mass (kg), and percent body fat was measured using a bio-impedance segmental
      body composition analyzer. Forced vital capacity (FVC) and forced expiratory
      volume in one second (FEV1) were measured by Quark PFT2 spirometer. RESULTS: The
      anthropometric measurements revealed that male triathletes were significantly
      taller than female triathletes and had significantly more protein and skeletal
      muscle mass. The female triathletes, however, had significantly higher percent
      body fat. Male triathletes had statistically significant higher FVC and FEV1 than
      female triathletes. Both the male and female triathletes showed a positive
      correlation between height, fat free mass and the lung function markers FVC and
      FEV1. This association was not seen with Body Mass Index (BMI) in female
      triathletes. CONCLUSIONS: The data from our study shows that anthropometric
      parameters are directly linked to lung function of a triathlete. We also found
      the relationship between BMI and lung function to be gender specific in
      triathletes and is dependent on the body protein and fat content. Hence, body
      composition characterization is essential and provides valuable information for
      developing individual specific training modules.

PMID- 27045743
TI  - Aerial Surveys of Elevated Hydrocarbon Emissions from Oil and Gas Production
      Sites.
AB  - Oil and gas (O&G) well pads with high hydrocarbon emission rates may
      disproportionally contribute to total methane and volatile organic compound (VOC)
      emissions from the production sector. In turn, these emissions may be missing
      from most bottom-up emission inventories. We performed helicopter-based infrared
      camera surveys of more than 8000 O&G well pads in seven U.S. basins to assess the
      prevalence and distribution of high-emitting hydrocarbon sources (detection
      threshold ~ 1-3 g s(-1)). The proportion of sites with such high-emitting sources
      was 4% nationally but ranged from 1% in the Powder River (Wyoming) to 14% in the
      Bakken (North Dakota). Emissions were observed three times more frequently at
      sites in the oil-producing Bakken and oil-producing regions of mixed basins (p <
      0.0001, chi(2) test). However, statistical models using basin and well pad
      characteristics explained 14% or less of the variance in observed emission
      patterns, indicating that stochastic processes dominate the occurrence of high
      emissions at individual sites. Over 90% of almost 500 detected sources were from
      tank vents and hatches. Although tank emissions may be partially attributable to
      flash gas, observed frequencies in most basins exceed those expected if emissions
      were effectively captured and controlled, demonstrating that tank emission
      control systems commonly underperform. Tanks represent a key mitigation
      opportunity for reducing methane and VOC emissions.

PMID- 27045744
TI  - Potential role of the soluble form of CD40 in deficient immunological function of
      dialysis patients: new findings of its amelioration using polymethylmethacrylate
      (PMMA) membrane.
AB  - Even though numerous studies have helped to better delineate abnormalities of
      either innate or adaptive immune system in end-stage renal disease (ESRD)
      patients, understanding immune dysfunctions in ESRD patients remains a very
      complex puzzle with missing pieces. In this context, we showed that the soluble
      form of CD40 (sCD40) is elevated in ESRD patients and is associated with a lack
      of response to hepatitis B vaccination. Interestingly, although most dialysis
      membranes are unable to clear sCD40, we demonstrated that polymethylmethacrylate
      (PMMA) BK-F membranes (Toray Medical Company, Japan) allow a dramatic diminution
      of the molecule. We took advantage of this observation to address the question of
      the potential usefulness of PMMA membrane (BK-F series) in the improvement of
      humoral immune response of ESRD patients. We, thus, present our recent data
      highlighting the potential role of BK-F membrane in the improvement of hepatitis
      B vaccination of ESRD patients who failed to mount a protective immune response
      despite one or more well-conducted anterior vaccination. Taken as a whole, our
      findings reinforced the concept of seeing dialysis membranes not just as a simple
      diffusive device but as a tool to tailor dialysis procedure to improve the global
      quality of life of ESRD patients. This opens a wide area of investigation,
      notably for the management of immunological dysfunction of ESRD patients.

PMID- 27045745
TI  - Mohs Micrographic Surgery for Less Common Cutaneous Malignancies: Is There a
      Practice Gap?

PMID- 27045746
TI  - Utilizing Mohs Surgery for Tissue Preservation in Erosive Adenomatosis of the
      Nipple.

PMID- 27045747
TI  - Skin Cancer Prevention and Treatment in Solid Organ Transplant Patients: A Survey
      of the International Transplant Skin Cancer Collaborative.

PMID- 27045748
TI  - Commentary on a Simple Elastomer-Pad Vibratory Dampener to Maximize Pain Control
      of Injections in Patients' Undergoing Dermatological Surgery.

PMID- 27045749
TI  - Endophytic fungi from selected varieties of soybean (Glycine max L. Merr.) and
      corn (Zea mays L.) grown in an agricultural area of Argentina.
AB  - Endophytic fungi are ubiquitous and live within host plants without causing any
      noticeable symptoms of disease. Little is known about the diversity and function
      of fungal endophytes in plants, particularly in economically important species.
      The aim of this study was to determine the identity and diversity of endophytic
      fungi in leaves, stems and roots of soybean and corn plants and to determine
      their infection frequencies. Plants were collected in six areas of the provinces
      of Buenos Aires and Entre Rios (Argentina) two areas were selected for sampling
      corn and four for soybean. Leaf, stem and root samples were surface-sterilized,
      cut into 1cm(2) pieces using a sterile scalpel and aseptically transferred to
      plates containing potato dextrose agar plus antibiotics. The species were
      identified using both morphological and molecular data. Fungal endophyte
      colonization in soybean plants was influenced by tissue type and varieties
      whereas in corn plants only by tissue type. A greater number of endophytes were
      isolated from stem tissues than from leaves and root tissues in both species of
      plants. The most frequently isolated species in all soybean cultivars was
      Fusarium graminearum and the least isolated one was Scopulariopsis brevicaulis.
      Furthermore, the most frequently isolated species in corn plants was Aspergillus
      terreus whereas the least isolated one was Aspergillus flavus. These results
      could be relevant in the search for endophytic fungi isolates that could be of
      interest in the control of agricultural pests. 

PMID- 27045750
TI  - Women Exiting Street-Based Sex Work: Correlations between Ethno-Racial Identity,
      Number of Children, and Violent Experiences.
AB  - Through this article the authors examine data collected from 126 women seeking
      services at a transitional housing facility, primarily for women leaving street
      based prostitution. Descriptive statistics on the women's ethno-racial identity,
      numbers of children, and experiences with violence are presented and analyzed to
      determine correlations and implications for social service providers working with
      this unique population of women. Nearly half of respondents are women of color, a
      majority have given birth to at least one child, and more than half are in a non
      commercial intimate partnership, with a significant number reporting extensive
      experiences with violent trauma and abuse. Results indicate statistically
      significant differences in women's ethno-racial self-identification and their
      experiences of sex work and violence, as well as their marital status. Most
      notably, African-American and Hispanic women face the greatest and most diverse
      forms of intimate partner violence and negative sex industry experiences, with
      African-Americans more likely to engage in sex work as minors, be sexually abused
      as children, work for a pimp, and face physical assault and instances of sex
      trafficking. Results also support existing research showing correlations between
      traumatic childhood events and adult substance abuse, sexual assault, and other
      negative outcomes. 

PMID- 27045751
TI  - Enhancement of ACE and prolyl oligopeptidase inhibitory potency of protein
      hydrolysates from sardine and tuna by-products by simulated gastrointestinal
      digestion.
AB  - This work was focused on the study of the bioactive potential of three fish
      protein hydrolysates, one of them prepared from industrial sardine by-products
      (head and viscera) and the others from tuna by-products (head, and muscle and
      viscera). These protein hydrolysates exhibited moderate ability to inhibit
      Angiotensin Converting Enzyme or ACE (IC50 between 0.24-1.16 mg dry weight per
      ml) and prolyl oligopeptidase or PO (IC50 between 3.30-9.57 mg ml(-1)), those
      obtained from tuna by-products being the most effective. Overall, ACE- and PO
      inhibiting activities were enhanced by sequential nanofiltration through 3 and 1
      kDa MWCO membranes (IC50 between 0.02-0.16 mg ml(-1) (ACE) and 1.10-4.21 mg ml(
      1) (PO)). The inhibitory properties of the hydrolysates were greatly improved by
      in vitro gastric digestion, and were barely affected by further intestinal
      digestion. The digested tuna hydrolysates, mainly that from heads, proved to be
      the best source of PO- and ACE- inhibiting molecules (IC50 = 0.16 mg ml(-1) (ACE)
      and 1.04 mg ml(-1) (PO)) and could be potential new ingredients in food with
      interest in the prevention or treatment of cardiovascular and neurological
      diseases. 

PMID- 27045752
TI  - Copper Chloride Catalysis: Do MU4-Oxido Copper Clusters Play a Significant Role?
AB  - Copper chloride catalysis is a well-established field in organic and inorganic
      chemistry. However, in most cases a detailed mechanistic understanding of the
      individual reaction steps and identification of reactive intermediates are still
      missing. The present study reports the results of spectroscopic and spectrometric
      measurements that support formation of copper agglomerates during catalytic
      processes. The composition of CuCl2.2H2O in several coordinating solvents and the
      influence of basic coreagents such as NaO(t)Bu and K2CO3 on the structure in the
      solid state as well as in solution were investigated. Several experiments
      involving crystal structure determination, IR spectroscopy, and ultra-high
      resolution cryospray-ionization mass spectrometry were performed. The crystal
      structures of [CuCl2(H2O)].0.5(CH3)2CO (1), [Cu2(CH3CN)2Cl4] (2),
      [Cu3(CH3CN)3Cl6] (3), [Cu3Cl6(THF)4] (4), [Cu(DMSO)2Cl2] (5), (H2N(CH3)2)2[CuCl3]
      (6), and [Cu4OCl6(THF)(urea)3].3THF.urea (8) are reported herein. It can be
      clearly demonstrated that MU4-oxido copper clusters of the formula
      [Cu4OCl6(solvent)4] are the main product from the reactions of CuCl2.2H2O and
      basic coreagents. As a final result of these experiments, it can be stated that
      MU4-oxido copper clusters most likely play an important role in the mechanism of
      copper chloride-catalyzed reactions. 

PMID- 27045753
TI  - Hyaluronidase activity in the salivary glands of tabanid flies.
AB  - Tabanids are haematophagous insects that act as biological and mechanical vectors
      of various diseases, including viruses, bacteria and parasites. The saliva of
      these insects contains strong anticoagulant and vasodilatory activities as well
      as immunoregulatory peptides. Here we demonstrate pronounced hyaluronidase
      (hyase) activity in ten tabanid species of the genera Chrysops, Haematopota,
      Hybomitra and Tabanus. Compared to other haematophagous insects, the ability of
      tabanid hyases to hydrolyze hyaluronic acid (HA) is extremely high, for example
      the enzyme activity of Hybomitra muehlfeldi was found to be 32-fold higher than
      the salivary hyase activity of the sand fly Phlebotomus papatasi. Hyases of all
      ten tabanid species tested also cleaved chondroitin sulfate A, another
      glycosaminoglycan present in the extracellular matrix of vertebrates. The pH
      optimum of the enzyme activity was measured in eight tabanid species; the hyase
      of Haemopota pluvialis was the only one with optimum at pH 4.0, while in the
      other seven species the activity optimum was at 5.0. SDS PAGE zymography showed
      the monomeric character of the enzymes in all tabanid species tested. Under non
      reducing conditions the activities were visible as single bands with estimated MW
      between 35 and 52 kDa. The very high hyaluronidase activity in tabanid saliva
      might be related to their aggressive biting behavior as well as to their high
      efficiency as mechanical vectors. As they are supposedly involved in the
      enlargement of feeding hematomas, hyases might contribute to the mechanical
      transmission of pathogens. Pathogens present in vector mouthparts are co
      inoculated into the vertebrate host together with saliva and may benefit from
      increased tissue permeability and the immunomodulatory activity of the salivary
      hyase. 

PMID- 27045754
TI  - Selenoprotein Transcript Level and Enzyme Activity as Biomarkers for Selenium
      Status and Selenium Requirements of Chickens (Gallus gallus).
AB  - The NRC selenium (Se) requirement for broiler chicks is 0.15 MUg Se/g diet, based
      primarily on weight gain and feed intake studies reported in 1986. To determine
      Se requirements in today's rapidly growing broiler chick, day-old male chicks
      were fed Se-deficient basal diets supplemented with graded levels of Se (0,
      0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.5, 0.75, and 1.0 MUg Se/g) as Na2SeO3
      (5/treatment). Diets contained 15X the vitamin E requirement, and there were no
      gross signs of Se-deficiency. At 29 d, Se-deficient chicks weighed 62% of Se
      supplemented chicks; 0.025 MUg Se/g reversed this effect, indicating a minimum Se
      requirement of 0.025 MUg Se/g diet for growth for male broiler chicks. Enzyme
      activities in Se-deficient chicks for plasma GPX3, liver and gizzard GPX1, and
      liver and gizzard GPX4 decreased dramatically to 3, 2, 5, 10 and 5%,
      respectively, of Se-adequate levels, with minimum Se requirements of 0.10-0.13
      MUg Se/g, and with defined plateaus above these levels. Pancreas GPX1 and GPX4
      activities, however, lacked defined plateaus, with breakpoints at 0.3 MUg Se/g.
      qPCR measurement of all 24 chicken selenoprotein transcripts, plus SEPHS1, found
      that SEPP1 in liver, GPX3 in gizzard, and SEPP1, GPX3 and SELK in pancreas were
      expressed at levels comparable to housekeeping transcripts. Only 33%, 25% and 50%
      of selenoprotein transcripts were down-regulated significantly by Se deficiency
      in liver, gizzard and pancreas, respectively. No transcripts could be used as
      biomarkers for supernutritional Se status. For export selenoproteins SEPP1 and
      GPX3, tissue distribution, high expression and Se-regulation clearly indicate
      unique Se metabolism, which may underlie tissues targeted by Se deficiency. Based
      on enzyme activities in liver, gizzard, and plasma, the minimum Se requirement in
      today's broiler chick is 0.15 MUg Se/g diet; pancreas data indicate that the Se
      requirement should be raised to 0.2 MUg Se/g diet to provide a margin of safety. 

PMID- 27045755
TI  - Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples
      Identified by Transcriptome Sequencing.
AB  - ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond
      to crizotinib, but resistance occurs inevitably. In this study we aimed to
      identify fusion genes in crizotinib resistant tumor samples. Re-biopsies of three
      patients were subjected to paired-end RNA sequencing to identify fusion genes
      using deFuse and EricScript. The IGV browser was used to determine presence of
      known resistance-associated mutations. Sanger sequencing was used to validate
      fusion genes and digital droplet PCR to validate mutations. ALK fusion genes were
      detected in all three patients with EML4 being the fusion partner. One patient
      had no additional fusion genes. Another patient had one additional fusion gene,
      but without a predicted open reading frame (ORF). The third patient had three
      additional fusion genes, of which two were derived from the same chromosomal
      region as the EML4-ALK. A predicted ORF was identified only in the CLIP4-VSNL1
      fusion product. The fusion genes validated in the post-treatment sample were also
      present in the biopsy before crizotinib. ALK mutations (p.C1156Y and p.G1269A)
      detected in the re-biopsies of two patients, were not detected in pre-treatment
      biopsies. In conclusion, fusion genes identified in our study are unlikely to be
      involved in crizotinib resistance based on presence in pre-treatment biopsies.
      The detection of ALK mutations in post-treatment tumor samples of two patients
      underlines their role in crizotinib resistance. 

PMID- 27045756
TI  - TPH1 and 5-HTTLPR Genes Specifically Interact in Opiate Dependence but Not in
      Alcohol Dependence.
AB  - BACKGROUND: Different drug dependencies may have unique genetic vulnerabilities.
      Changes in serotonin availability and function have been linked to addiction. We
      investigated whether 2 serotonergic polymorphisms, TPH1 A218C (rs1800532) and 5
      HTT-linked promoter region (5-HTTLPR) (rs25531), are differently associated with
      alcohol or opiate dependence. METHODS: Alcohol-dependent patients (n = 292),
      opiate-dependent patients (n = 309), and healthy controls (n = 301) were
      recruited from the Han Chinese population in Taiwan. Genotypes of TPH1 A218C and
      5-HTTLPR polymorphisms were analyzed using a polymerase chain reaction with
      restriction fragment length polymorphism. RESULTS: The genotype frequencies of
      the TPH1 A218C polymorphisms were not significantly different in the 3 groups.
      The genotype frequencies of the 5-HTTLPR S+ (S/S, S/LG, LG/LG) polymorphisms were
      significantly higher in opiate-dependent patients (x03C7;2 = 8.77, p = 0.01), but
      not after controlling for the covariates of age, gender, and interaction effect
      in logistic regression analysis. Moreover, there was a significant interaction
      between the TPH1 A218C A/C and 5-HTTLPR S+ gene polymorphisms in opiate-dependent
      (OR 2.72, p = 0.01), but not in alcohol-dependent patients. CONCLUSIONS: Our data
      suggested that there may be a differential genetic vulnerability in serotonergic
      genes for alcohol and opiate addiction. However, replications of our findings are
      still needed.

PMID- 27045757
TI  - Implementation of Analytical Energy Gradient of Spin-Dependent General Hartree
      Fock Method Based on the Infinite-Order Douglas-Kroll-Hess Relativistic
      Hamiltonian with Local Unitary Transformation.
AB  - An analytical energy gradient for the spin-dependent general Hartree-Fock method
      based on the infinite-order Douglas-Kroll-Hess (IODKH) method was developed. To
      treat realistic systems, the local unitary transformation (LUT) scheme was
      employed both in energy and energy gradient calculations. The present energy
      gradient method was numerically assessed to investigate the accuracy in several
      diatomic molecules containing fifth- and sixth-period elements and to examine the
      efficiency in one-, two-, and three-dimensional silver clusters. To arrive at a
      practical calculation, we also determined the geometrical parameters of fac
      tris(2-phenylpyridine)iridium and investigated the efficiency. The numerical
      results confirmed that the present method describes a highly accurate
      relativistic effect with high efficiency. The present method can be a powerful
      scheme for determining geometries of large molecules, including heavy-element
      atoms. 

PMID- 27045758
TI  - Relevance and Significance of Extraterrestrial Abiological Hydrocarbon Chemistry.
AB  - Astrophysical observations show similarity of observed abiological "organics"
      i.e., hydrocarbons, their derivatives, and ions (carbocations and carbanions)
      with studied terrestrial chemistry. Their formation pathways, their related
      extraterrestrial hydrocarbon chemistry originating from carbon and other elements
      after the Big Bang, their parent hydrocarbon and derivative (methane and
      methanol, respectively), and transportation of derived building blocks of life by
      meteorites or comets to planet Earth are discussed in this Perspective. Their
      subsequent evolution on Earth under favorable "Goldilocks" conditions led to more
      complex molecules and biological systems, and eventually to humans. The relevance
      and significance of extraterrestrial hydrocarbon chemistry to the limits of
      science in relation to the physical aspects of evolution on our planet Earth are
      also discussed.

PMID- 27045759
TI  - Intraspecific Variation in Carotenoids of Brassica oleracea var. sabellica.
AB  - Carotenoids are best known as a source of natural antioxidants. Physiologically,
      carotenoids are part of the photoprotection in plants as they act as scavengers
      of reactive oxygen species (ROS). An important source of carotenoids in European
      food is Brassica oleracea. Focusing on the most abundant carotenoids, we
      estimated the contents of beta-carotene, (9Z)-neoxanthin, zeaxanthin, and lutein
      as well as those of chlorophylls a and b to assess their variability in Brassica
      oleracea var. sabellica. Our analyses included more than 30 cultivars categorized
      in five distinct sets grouped according to morphological characteristics or
      geographical origin. Our results demonstrated specific carotenoid patterns
      characteristic for American, Italian, and red-colored kale cultivars. Moreover,
      we demonstrated a tendency of high zeaxanthin proportions under traditional
      harvest conditions, which accord to low-temperature regimes. We also compared the
      carotenoid patterns of self-generated hybrid lines. Corresponding findings
      indicated that crossbreeding has a high potential for carotenoid content
      optimization in kale. 

PMID- 27045760
TI  - Reducing Short-Wavelength Blue Light in Dry Eye Patients with Unstable Tear Film
      Improves Performance on Tests of Visual Acuity.
AB  - PURPOSE: To investigate whether suppression of blue light can improve visual
      function in patients with short tear break up time (BUT) dry eye (DE). METHODS:
      Twenty-two patients with short BUT DE (10 men, 12 women; mean age, 32.4 +/- 6.4
      years; age range, 23-43 years) and 18 healthy controls (10 men, 8 women; mean
      age, 30.1 +/- 7.4 years; age range, 20-49 years) underwent functional visual
      acuity (VA) examinations with and without wearing eyeglasses with 50% blue light
      blocked lenses. The functional VA parameters were starting VA, functional VA, and
      visual maintenance ratio. RESULTS: The baseline mean values (logarithm of the
      minimum angle of resolution, logMAR) of functional VA and the visual maintenance
      ratio were significantly worse in the DE patients than in the controls (P <
      0.05), while no significant difference was observed in the baseline starting VA
      (P > 0.05). The DE patients had significant improvement in mean functional VA and
      visual maintenance ratio while wearing the glasses (P < 0.05), while there were
      no significant changes with and without the glasses in the control group (P >
      0.05). CONCLUSIONS: Protecting the eyes from short-wavelength blue light may help
      to ameliorate visual impairment associated with tear instability in patients with
      DE. This finding represents a new concept, which is that the blue light exposure
      might be harmful to visual function in patients with short BUT DE.

PMID- 27045761
TI  - Serelaxin for the treatment of heart failure.
AB  - Outcomes for patients with acute heart failure remain suboptimal and treatments
      principally target improvement of symptoms. To date there has been no therapy
      approved for acute heart failure shown to improve mortality or readmission risk
      post-discharge. Serelaxin, a recombinant form of the naturally occurring
      polypeptide hormone relaxin, has demonstrated promise in preclinical and early
      clinical trials as a potentially novel therapy for acute heart failure. It is
      postulated through its anti-fibrotic and vasodilatory effects that this agent can
      improve outcomes in both the short and long term in these patients. Randomized
      clinical data has suggested that the medication is safe and well tolerated.
      However, definitive outcomes data is currently being assessed in a large multi
      center trial. 

PMID- 27045762
TI  - Corynebacterium lowii sp. nov. and Corynebacterium oculi sp. nov., derived from
      human clinical disease and an emended description of Corynebacterium mastitidis.
AB  - Strains of members of the genus Corynebacterium derived from ophthalmologic
      patients in Japan, Belgium and Switzerland and found to be closely related to-,
      but distinguishable from Corynebacterium mastitidis by 16S rRNA gene sequencing,
      were characterized using biochemical, chemotaxonomic, MALDI-TOF mass spectrometry
      and antimicrobial susceptibility methods and DNA-DNA hybridization as well as by
      whole-genome sequencing (WGS). Based on this investigation, we describe
      Corynebacterium lowii sp. nov. and Corynebacterium oculi sp. nov., derived from
      human ocular specimens, as well as emend the description of Corynebacterium
      mastitidis. Type strains for these species are: C. lowii R-50085T (=LMG 28276T
      =CCUG 65815T) and C. oculi R-50187T (=LMG 28277T =CCUG 65816T). DNA G+C content
      was found to be 62.2 % (by HPLC) and 62.8 % (by WGS) for C. lowii R-50085T, 64.1
      % (HPLC) and 64.8 % (WGS) for C. oculi R-50187T and 67.8 % (HPLC) for C.
      mastitidis LMG 19040T [=S-8T =CCUG 38654T =CECT 4843T =CIP 105509T =DSM 44356T
      =IFO (NBRC)16160T =JCM 12269T]. 

PMID- 27045763
TI  - Historical and Current Perspectives on the Systematics of the 'Enigmatic' Diatom
      Genus Rhoicosphenia (Bacillariophyta), with Single and Multi-Molecular Marker and
      Morphological Analyses and Discussion on the Monophyly of 'Monoraphid' Diatoms.
AB  - This study seeks to determine the phylogenetic position of the diatom genus
      Rhoicosphenia. Currently, four hypotheses based on the morphology of the
      siliceous valve and its various ultrastructural components, sexual reproduction,
      and chloroplasts have been proposed. Two previous morphological studies have
      tentatively placed Rhoicosphenia near members of the Achnanthidiaceae and
      Gomphonemataceae, and no molecular studies have been completed. The position of
      Rhoicosphenia as sister to 'monoraphid' diatoms is problematic due to the
      apparent non-monophyly of that group, so hypotheses of 'monoraphid' monophyly are
      also tested. Using an analysis of morphological and cytological features, as well
      as sequences from three genes, SSU, LSU, and rbcL, recovered from several
      freshwater Rhoicosphenia populations that have similar morphology to
      Rhoicosphenia abbreviata (Agardh) Lange-Bertalot, we have analyzed the
      phylogenetic position of Rhoicosphenia in the context of raphid diatoms. Further,
      we have used topology testing to determine the statistical likelihoods of these
      relationships. The hypothesis that Rhoicosphenia is a member of the
      Achnanthidiaceae cannot be rejected, while the hypothesis that it is a member of
      the Gomphonemataceae can be rejected. In our analyses, members of the
      Achnanthidiaceae are basal to Rhoicosphenia, and Rhoicosphenia is basal to the
      Cymbellales, or a basal member of the Cymbellales, which includes the
      Gomphonemataceae. Hypothesis testing rejects the monophyly of 'monoraphid'
      diatoms. 

PMID- 27045764
TI  - (90)Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from
      the Fukushima-Daiichi Nuclear Power Plant accident.
AB  - Here we determined the (90)Sr concentrations in the teeth of cattle abandoned in
      the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident.
      (90)Sr activity concentrations in the teeth varied from 6-831 mBq (g Ca)(-1) and
      exhibited a positive relationship with the degree of radioactive contamination
      that the cattle experienced. Even within an individual animal, the specific
      activity of (90)Sr (Bq (g Sr)(-1)) varied depending on the development stage of
      the teeth during the FNPP accident: teeth that were early in development
      exhibited high (90)Sr specific activities, while teeth that were late in
      development exhibited low specific activities. These findings demonstrate that
      (90)Sr is incorporated into the teeth during tooth development; thus, tooth
      (90)Sr activity concentrations reflect environmental (90)Sr levels during tooth
      formation. Assessment of (90)Sr in teeth could provide useful information about
      internal exposure to (90)Sr radiation and allow for the measurement of time
      course changes in the degree of environmental (90)Sr pollution. 

PMID- 27045765
TI  - Developmental Toxicity of Triclosan in the Presence of Dissolved Organic Carbon:
      Moving Beyond Standard Acute Toxicity Assays to Understand Ecotoxicological Risk.
AB  - Triclosan (TCS) is an ionizable synthetic antimicrobial that has been found to be
      a persistent environmental contaminant with potential for bioaccumulation.
      Standard laboratory assays have shown that TCS is toxic to aquatic organisms;
      however, varied environmental conditions could impact this risk. For example, we
      would predict that sorption to dissolved organic carbon (DOC) in natural surface
      waters would reduce the bioavailability and, therefore, toxicity of TCS. To
      better understand the potential risk that TCS poses to wild fish, we evaluated
      the toxicity of TCS to zebrafish in the presence of DOC. Zebrafish were exposed
      to TCS (0-900 MUg TCS/L), DOC (0-25 mg/L), or TCS (0-900 MUg TCS/L) together with
      either 10 or 25 mg DOC/L from 8 to 120 h postfertilization through static
      waterborne exposure. We compared impacts of TCS alone or in conjunction with DOC
      on mortality, development, and hatching success. Exposure to TCS in the presence
      of DOC improves survival and hatching success, and reduces the incidence of
      developmental toxicity. However, since the presence of DOC did not completely
      prevent sublethal toxicity, our data suggest that given its bioaccumulation
      potential, developmental toxicity of TCS under environmental conditions still
      warrants concern.

PMID- 27045766
TI  - Successful endovascular management of venous sinus thrombosis complicating trans
      labyrinthine removal of vestibular schwanomma.
AB  - Cerebral venous sinus thrombosis (CVST) is a rare complication of surgical
      treatment of vestibular schwanomma. We present a rare case of extensive venous
      sinus thrombosis after trans-labyrinthine approach that was refractory to
      systemic anti-coagulation. Mechanical aspiration thrombectomy was utilized to re
      canalize the venous sinuses and resulted in successful resolution of neurological
      symptoms. Indications of utilizing endovascular approaches are discussed that
      will enable skull base surgeons to address this uncommon yet potentially fatal
      complication. 

PMID- 27045767
TI  - Are neutrophil-, eosinophil-, and basophil-to-lymphocyte ratios useful markers
      for pinpointing patients at higher risk of recurrent sinonasal polyps?
AB  - PURPOSE: Despite advances in the diagnosis and treatment of chronic
      rhinosinusitis with nasal polyps (CRSwNP), their recurrence rate remains
      significant. There is a need for promptly-obtainable, inexpensive, minimally
      invasive prognostic parameters to enable rhinologists to identify patients at
      higher risk of recurrent CRSwNP. The prognostic role of the neutrophil-to
      lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR), previously
      discussed as potential markers of inflammation, has already been investigated in
      CRSwNP. The aim of the present study was to test the prognostic value of the NLR
      and ELR, and also of the basophil-to-lymphocyte ratio (BLR) (given the emerging
      role of basophils in CRSwNP) in a large series of CRSwNP. MATERIALS AND METHODS:
      The study concerned 240 patients who underwent FESS for CRSwNP from 2009 to 2014
      and had a postoperative follow-up longer than 12months. We considered patients
      with recurrences as those with endoscopic evidence of at least grade I polyposis.
      RESULTS: In our series, the mean NLR, ELR and BLR were significantly higher in
      patients whose disease recurred than in those remaining recurrence-free (p=0.03,
      p=0.0001, and p=0.0002, respectively), but the discriminatory power of the NLR,
      ELR, or BLR in terms of disease recurrence was unacceptable (AUCs=0.600, 0.678,
      and 0.662, respectively). CONCLUSIONS: The heterogeneous prognostic role of NLR,
      ELR and BLR identified in the clinically and pathologically different sub-cohorts
      of CRSwNP considered supports the hypothesis that CRSwNPs with a similar clinical
      picture may differ considerably in terms of the biological and pathogenic
      mechanisms of polyp formation and growth.

PMID- 27045768
TI  - Carbapenem-Resistant Acinetobacter baumannii: Concomitant Contamination of Air
      and Environmental Surfaces.
AB  - OBJECTIVE To concomitantly determine the differential degrees of air and
      environmental contamination by Acinetobacter baumannii based on anatomic source
      of colonization and type of ICU layout (single-occupancy vs open layout). DESIGN
      Longitudinal prospective surveillance study of air and environmental surfaces in
      patient rooms. SETTING A 1,500-bed public teaching hospital in Miami, Florida.
      PATIENTS Consecutive A. baumannii-colonized patients admitted to our ICUs between
      October 2013 and February 2014. METHODS Air and environmental surfaces of the
      rooms of A. baumannii-colonized patients were sampled daily for up to 10 days.
      Pulsed-field gel electrophoresis (PFGE) was used to type and match the matching
      air, environmental, and clinical A. baumannii isolates. RESULTS A total of 25 A.
      baumannii-colonized patients were identified during the study period; 17 were
      colonized in the respiratory tract and 8 were colonized in the rectum. In rooms
      with rectally colonized patients, 38.3% of air samples were positive for A.
      baumannii; in rooms of patients with respiratory colonization, 13.1% of air
      samples were positive (P=.0001). In rooms with rectally colonized patients, 15.5%
      of environmental samples were positive for A. baumannii; in rooms of patients
      with respiratory colonization, 9.5% of environmental samples were positive
      (P=.02). The rates of air contamination in the open-layout and single-occupancy
      ICUs were 17.9% and 21.8%, respectively (P=.5). Environmental surfaces were
      positive in 9.5% of instances in open-layout ICUs versus 13.4% in single
      occupancy ICUs (P=.09). CONCLUSIONS Air and environmental surface contaminations
      were significantly greater among rectally colonized patients; however, ICU layout
      did not influence the rate of contamination. Infect Control Hosp Epidemiol
      2016;37:777-781.

PMID- 27045769
TI  - Digestive sensitivity varies according to size of dogs: a review.
AB  - Field observations on food tolerance have repeatedly shown that when fed an
      identical diet, large breed (>25 kg) dogs present softer and moister faeces than
      small breed ones (<15 kg). The purpose of this review is to highlight the
      findings of four PhD theses, carried out between 1998 and 2013, whose objectives
      were to investigate the anatomical and physiological peculiarities that would
      explain, at least in part, this observation, as well as their nutritional
      implication. This work showed that large breed dogs, in contrast with smaller
      breeds, present a highly developed caecum and colon, which could explain the
      relatively longer colonic transit time. A prolonged colonic transit time could
      explain higher colonic fermentative activity, as supported by higher faecal
      concentrations of fermentative by-products. This effect would be reinforced by
      increased intestinal permeability and reduced sodium net-absorption. Taken
      together, these elements could be a possible cause of higher digestive
      sensitivity in large breed dogs. When prescribing a diet to a small or large
      breed dog, several aspects of the formulation must be taken into account. For a
      large breed dog, the general goal is to limit any ingredient that could increase
      the level of fermentable undigested residues and, in fine, exacerbate colonic
      fermentation. Highly digestible sources of proteins and starches are therefore
      strongly recommended to maintain an optimal digestive tolerance. Fermentable
      fibre sources (i.e. beet pulp and FOS) must also be used in limited quantity in
      their diet. Conversely, the incorporation of non-fermentable fibre (i.e.
      cellulose) appears useful to increase their stool quality. For a small breed dog,
      the general objective is to minimize any ingredient that could excessively limit
      colonic fermentation and induce in fine constipation. Purified starches and
      cellulose are therefore not really suitable for them. In contrast, cereals flours
      as well as non-fermentable fibre provided by cereals are recommended.

PMID- 27045770
TI  - Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor
      Tissue: Effect of Nanoparticle Aspect Ratio.
AB  - Nanoparticle-based technologies, including platforms derived from plant viruses,
      hold great promise for targeting and delivering cancer therapeutics to solid
      tumors by overcoming dose-limiting toxicities associated with chemotherapies. A
      growing body of data indicates advantageous margination and penetration
      properties of high aspect-ratio nanoparticles, which enhance payload delivery,
      resulting in increased efficacy. Our lab has demonstrated that elongated rod
      shaped and filamentous macromolecular nucleoprotein assemblies from plant viruses
      have higher tissue diffusion rates than spherical particles. In this study, we
      developed a mathematical model to quantify diffusion and uptake of tobacco mosaic
      virus (TMV) in a spheroid system approximating a capillary-free segment of a
      solid tumor. Model simulations predict TMV concentration distribution with time
      in a tumor spheroid for different sizes and cell densities. From simulations of
      TMV concentration distribution, we can quantify the effect of TMV aspect ratio
      (e.g., nanorod length-to-width) with and without cellular uptake by modulated
      surface chemistry. This theoretical analysis can be applied to other viral or
      nonviral delivery systems to complement the experimental development of the next
      generation of nanotherapeutics.

PMID- 27045771
TI  - Measurements of Monoclonal Antibody Self-Association Are Correlated with Complex
      Biophysical Properties.
AB  - Successful development of monoclonal antibodies (mAbs) for therapeutic
      applications requires identification of mAbs with favorable biophysical
      properties (high solubility and low viscosity) in addition to potent
      bioactivities. Nevertheless, mAbs can also display complex, nonconventional
      biophysical properties that impede their development such as formation of soluble
      aggregates and subvisible particles as well as nonspecific interactions with
      various types of surfaces such as nonadsorptive chromatography columns. Here we
      have investigated the potential of using antibody self-interaction measurements
      obtained via affinity-capture self-interaction nanoparticle spectroscopy (AC
      SINS) at dilute concentrations (0.01 mg/mL) for ranking a panel of 12 mAbs in
      terms of their expected biophysical properties at higher concentrations (1-30
      mg/mL). Several mAb properties (solubility, % monomer, size-exclusion elution
      time and % recovery) displayed modest correlation with each other, as some mAbs
      with deficiencies in one or more properties (e.g., solubility) failed to show
      deficiencies in other properties (e.g., % monomer). The ranking of mAbs in terms
      of their level of self-association was correlated with their solubility ranking.
      However, the correlation was even stronger between the average ranking of the
      four biophysical properties and the AC-SINS measurements. This finding suggests
      that weak self-interactions detected via AC-SINS can manifest themselves in
      different ways and lead to complex biophysical properties. Our findings highlight
      the potential for using high-throughput self-interaction measurements to improve
      the identification of mAbs that possess a collection of excellent biophysical
      properties without the need for cumbersome analysis of each individual property
      during early candidate selection.

PMID- 27045772
TI  - Identification of potential biomarkers of exposure to diundecyl phthalate.
AB  - Diundecyl phthalate (DUP) is a high production volume chemical used as a
      plasticizer in polyvinyl chloride and other plastics. Specific biomarkers of DUP
      would be useful for human exposure assessment. To identify such biomarkers, we
      investigated the in vitro metabolism of DUP with human liver microsomes using
      online solid phase extraction coupled to HPLC-mass spectrometry. Using high
      resolution mass spectrometry, we conclusively confirmed the structures of four
      DUP specific metabolites: monoundecyl phthalate (MUP), mono-hydroxyundecyl
      phthalate (MHUP), mono-oxoundecyl phthalate (MOUP), and mono-carboxydecyl
      phthalate (MCDP). We also used high resolution mass spectrometry to isolate MCDP
      and MHUP from co-eluting isobaric metabolites of diisononyl phthalate (i.e.,
      monocarboxyisononyl phthalate) and diisododecyl phthalate (i.e.,
      monohydroxyisododecyl phthalate), respectively, that could not be separated with
      low resolution tandem mass spectrometry. To evaluate the potential usefulness of
      the newly identified DUP metabolites as exposure biomarkers, we analyzed 36 human
      urine samples by high resolution mass spectrometry. We detected MHUP and MCDP in
      >83% of the samples; median concentrations were 0.21ng/mL and 0.36ng/mL,
      respectively. MOUP was detected only in 14% of the samples analyzed, and MUP was
      not detected. All three metabolites eluted as peak clusters likely because of the
      presence of multiple oxidation sites and multiple isomers in DUP technical
      mixtures. Taken together, these findings suggest that with the appropriate mass
      spectrometry quantification techniques, MHUP and MCDP may serve as suitable
      biomarkers for assessing background exposure to DUP.

PMID- 27045773
TI  - The complete mitochondrial genomes of four cockroaches (Insecta: Blattodea) and
      phylogenetic analyses within cockroaches.
AB  - Three complete mitochondrial genomes of Blaberidae (Insecta: Blattodea)
      (Gromphadorhina portentosa, Panchlora nivea, Blaptica dubia) and one complete mt
      genome of Blattidae (Insecta: Blattodea) (Shelfordella lateralis) were sequenced
      to further understand the characteristics of cockroach mitogenomes and
      reconstruct the phylogenetic relationship of Blattodea. The gene order and
      orientation of these four cockroach genomes were similar to known cockroach mt
      genomes, and contained 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA)
      genes, 22 transfer RNA (tRNA) genes and one control region. The mt genomes of
      Blattodea exhibited a characteristics of a high A+T composition (70.7%-74.3%) and
      dominant usage of the TAA stop codon. The AT content of the whole mt genome, PCGs
      and total tRNAs in G. portentosa was the lowest in known cockroaches. The
      presence of a 71-bp intergenic spacer region between trnQ and trnM was a unique
      feature in B. dubia, but absent in other cockroaches, which can be explained by
      the duplication/random loss model. Based on the nucleotide and amino acid
      datasets of the 13 PCGs genes, neighbor-joining (NJ), maximum parsimony (MP),
      maximum likelihood (ML) and bayesian inference (BI) analyses were used to rebuild
      the phylogenetic relationship of cockroaches. All phylogenetic analyses
      consistently placed Isoptera as the sister cluster to Cryptocercidae of
      Blattodea. Ectobiidae and Blaberidae (Blaberoidea) formed a sister clade to
      Blattidae. Corydiidae is a sister clade of all the remaining cockroach species
      with a high value in NJ and MP analyses of nucleotide and amino acid datasets,
      and ML and BI analyses of the amino acid dataset. 

PMID- 27045774
TI  - Identification of Aadnr1, a novel gene related to innate immunity and apoptosis
      in Aedes albopictus.
AB  - Innate immunity and apoptosis play critical roles in defending pathogens in
      insects. In Drosophila, Dnr1 was reported as a negative regulator of apoptosis
      and immune deficiency (Imd) pathway which belongs to innate immunity. Aedes
      albopictus is an important kind of arbovirus vector and becoming a significant
      threat to public health due to its rapid global expansion. Here we identified an
      ortholog of dnr1 from A. albopictus, named as Aadnr1. Aadnr1 encoded a putative
      protein containing an N-terminal FERM domain and a C-terminal RING domain. AaDnr1
      shared high identity with dipteran insects Dnr1 orthologs. Phylogenetic analyses
      showed that the closest relative of AaDnr1 was Aedes aegypti Dnr1. Real-time PCR
      proved that Aadnr1 mRNA was expressed ubiquitously during developmental and adult
      stages. Transcriptional levels of Aadnr1 were decreased drastically in C6/36
      cells underwent apoptosis induced by Actinomycin D (Act D) treatment. Partial
      silence of Aadnr1 enhanced Act D-induced caspase activity. When challenged by
      heat-inactivated E. coli, transcriptional level of Aadnr1 was also decreased
      dramatically in C6/36 cells. While when C6/36 cells were infected with Sindbis
      virus TE/GFP, transcriptional level of Aadnr1 was reduced and recovered
      repeatedly, with an overall decreasing trend. It was also shown in this study
      that similar to Drosophila Dnr1, RING domain destabilized AaDnr1 protein. Taken
      together, the study identified an innate immunity and apoptosis related gene
      Aadnr1 in A. albopictus. 

PMID- 27045777
TI  - Prognostic factors for overall survival in elderly patients with advanced ovarian
      cancer treated with chemotherapy: Results of a pooled analysis of three GINECO
      phase II trials.
AB  - BACKGROUND: The GINECO led three multicentric prospective phase II studies,
      Elderly Woman Ovarian Trials 1 (EWOT1), EWOT2, and EWOT3, to evaluate the impact
      of geriatric covariates on the outcome of elderly patients treated with six
      courses of first-line chemotherapy for FIGO stage IIIIV ovarian cancer. This
      pooled analysis was designed to evaluate the validity of the geriatric
      vulnerability parameters identified in EWOT3 (Falandry et al., 2013). PATIENTS
      AND METHODS: From 1997 to 2011, 266 patients were recruited: 83 in EWOT1, 72 in
      EWOT2, and 111 in EWOT3, which evaluated respectively a 4-weekly carboplatin
      cyclophosphamide regimen, a 3-weekly standard carboplatin-paclitaxel doublet and
      a carboplatin monotherapy. All patients were analyzed in this pooled analysis for
      treatment completion, toxicity, and overall survival. RESULTS: The global
      treatment completion rate was 73% and ranged from 68% in EWOT2 to 74% in EWOT3.
      Toxicities were generally manageable: neutropenia was more frequent in EWOT2 and
      thrombopenia in EWOT1 and EWOT3. In multivariate analysis, covariates associated
      with decreased survival were: being "depressed" according to the investigators'
      assessment, hypoalbuminemia <35g/L, and FIGO stage IV. In addition, a Hospital
      Anxiety and Depression Scale (HADS) score>14 and Instrumental Activities of Daily
      Living (IADL) score<25 confirmed a deleterious impact in the EWOT2+EWOT3
      population subanalysis. CONCLUSIONS: Despite moderate heterogeneity among the
      studies, this pooled analysis confirmed the deleterious effects on overall
      survival of emotional disorders ("depressed", as assessed by investigators or the
      HADS score), and decreased functionality (IADL score), in addition to FIGO stage.

PMID- 27045776
TI  - Global Isotope Metabolomics Reveals Adaptive Strategies for Nitrogen
      Assimilation.
AB  - Nitrogen cycling is a microbial metabolic process essential for global
      ecological/agricultural balance. To investigate the link between the well
      established ammonium and the alternative nitrate assimilation metabolic pathways,
      global isotope metabolomics was employed to examine three nitrate reducing
      bacteria using (15)NO3 as a nitrogen source. In contrast to a control
      (Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak
      Ridge, Tennessee (Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for
      assimilation concurrently with differential labeling observed across multiple
      classes of metabolites including amino acids and nucleotides. The data reveal
      that the N2A2 and N2E2 strains conserve nitrogen-containing metabolites,
      indicating that the nitrate assimilation pathway is a conservation mechanism for
      the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an
      adaption to manage higher levels of nitrite since the denitrification pathways
      utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to
      the accumulation of the toxic nitrite. The use of global isotope metabolomics
      allowed for this adaptive strategy to be investigated, which would otherwise not
      have been possible to decipher.

PMID- 27045778
TI  - Correction: Maternal BMI Associations with Maternal and Cord Blood Vitamin D
      Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome
      (HAPO) Study Participants.

PMID- 27045779
TI  - The topological Anderson insulator phase in the Kane-Mele model.
AB  - It has been proposed that adding disorder to a topologically trivial mercury
      telluride/cadmium telluride (HgTe/CdTe) quantum well can induce a transition to a
      topologically nontrivial state. The resulting state was termed topological
      Anderson insulator and was found in computer simulations of the Bernevig-Hughes
      Zhang model. Here, we show that the topological Anderson insulator is a more
      universal phenomenon and also appears in the Kane-Mele model of topological
      insulators on a honeycomb lattice. We numerically investigate the interplay of
      the relevant parameters, and establish the parameter range in which the
      topological Anderson insulator exists. A staggered sublattice potential turns out
      to be a necessary condition for the transition to the topological Anderson
      insulator. For weak enough disorder, a calculation based on the lowest-order Born
      approximation reproduces quantitatively the numerical data. Our results thus
      considerably increase the number of candidate materials for the topological
      Anderson insulator phase. 

PMID- 27045780
TI  - Toward a Scholarly Etiquette: How to Keep Your Scholarly Interactions Prolific,
      Respectful, and Kind.

PMID- 27045782
TI  - Safety assessment of molecular targeted therapies in association with
      radiotherapy in metastatic renal cell carcinoma: a real-life report.
AB  - Molecular targeted therapies (TT) are the cornerstone of metastatic renal cell
      carcinoma (RCC) treatment. There is a paucity of data on the safety of the
      radiotherapy (RT)-TT association in a sequential or a concomitant setting. The
      aim of the present study is to retrospectively assess the safety of the RT-TT
      association. From 2006 to 2014, data from 84 consecutive patients treated with RT
      and TT for metastatic RCC were retrospectively collected. RT-TT sequential and
      concomitant associations were, respectively, defined by a time interval of more
      than five TT half-lives and less than or equal to five TT half-lives between the
      last TT administration and RT initiation. Toxicities in the fields of RT were
      assessed systematically. As many patients received several TT and RT courses, 136
      RT-TT associations were analyzed, with 66 sequential and 70 concomitant schemes.
      RT was mainly delivered on bone (75%) and brain metastases (14.7%). TT were
      tyrosine kinase inhibitors (73.5%), mTOR inhibitors (19.8%), and monoclonal
      antibodies (6.7%). With a median follow-up of 9.5 months, whatever the sequence,
      no grade>=4 toxicity was reported. Two grade 3 toxicities were reported with
      sequential (3%) and concomitant (2.9%) RT-TT, respectively. Sequential or
      concomitant RT-TT associations in metastatic RCC do not seem to cause major
      toxicity. 

PMID- 27045783
TI  - CO2 laser photoacoustic measurements of ethanol absorption coefficients within
      infrared region of 9.2-10.8 MUm.
AB  - Absorption coefficients of the ethanol vapors at atmospheric pressure and room
      temperature were measured by photoacoustic technique using a cw, line-tunable,
      frequency-stabilized CO2 laser as radiation source. The spectrum of the employed
      CO2 laser includes 54 lines with wavelengths in the infrared region of 9.2
      10.8MUm and power levels up to 4.7W. Measurements revealed a predominant
      absorption for ethanol within 9.4MUm band of the CO2 laser spectrum, where the
      highest values of the absorption coefficients were recorded: 3.68cm(-1)atm(-1) at
      9R(20) line and 3.65cm(-1)atm(-1) at 9R(22) line. The estimated detection range
      covers six orders of magnitude, from a minimum of 30ppbV to a maximum of 4%
      concentration of ethanol in nitrogen, which proves the suitability of the
      photoacoustic technique for accurate measurements of the ethanol concentration in
      various applications. 

PMID- 27045784
TI  - A new and highly selective turn-on fluorescent sensor with fast response time for
      the monitoring of cadmium ions in cosmetic, and health product samples.
AB  - Cadmium (Cd) which is an extremely toxic could be found in many products like
      plastics, fossil fuel combustion, cosmetics, water resources, and wastewaters. It
      is capable of causing serious environmental and health problems such as lung,
      prostate, renal cancers and the other disorders. So, the development of a sensor
      to continually monitor cadmium is considerably demanding. Tetrakis(4
      nitrophenyl)porphyrin, T(4-NO2-P)P, was synthesized and used as a new and highly
      selective fluorescent probe for monitoring cadmium ions in the "turn-on" mode.
      There was a linear relationship between fluorescence intensity and the
      concentration of Cd(II) in the range of 1.0*10(-6) to 1.0*10(-5)molL(-1) with a
      detection limit of 0.276MUM. To examine the most important parameters involved
      and their interactions in the sensor optimization procedure, a four-factor
      central composite design (CCD) combined with response surface modeling (RSM) was
      implemented. The practical applicability of the developed sensor was investigated
      using real cosmetic, and personal care samples. 

PMID- 27045785
TI  - Label free and high specific detection of mercury ions based on silver nano
      liposome.
AB  - Herein, we report an eco-friendly, mild and one-pot approach for synthesis of
      silver nanoparticles via a lipopeptide biosurfactant - CHBS. The biosurfactant
      forms liposome vesicles when dispersed in an aqueous medium. The amino acid
      groups of the biosurfactant assists in the reduction of Ag(+) ions leading to the
      production of homogeneous silver nanoparticles, encapsulated within the liposome
      vesicle, as confirmed from TEM analysis. Rate of synthesis and size of particle
      were greatly dependent on pH and reaction temperature. Kinetic analysis suggests
      the involvement of an autocatalytic reaction and the observed rate constant
      (kobs) was found to decrease with temperature, suggesting faster reaction with
      increasing temperature. Furthermore, the silver nanoparticles served as excellent
      probes for highly selective and sensitive recognition of Hg(2+) ions. Interaction
      with Hg(2+) ions results in an immediate change in colour of nanoparticle
      solution form brownish red to milky white. With increasing Hg(2+) ions
      concentration, a gradual disappearance of SPR peak was observed. A linear
      relationship (A420/660) with an R(2) value of 0.97 was observed in the range of
      20 to 100ppm Hg(2+) concentration. Hg(2+) ions are reduced to their elemental
      forms which thereby interact with the vesicles, leading to aggregation and
      precipitation of particles. The detection method avoids the need of
      functionalizing ligands and favours Hg(2+) detection in aqueous samples by
      visible range spectrophotometry and hence can be used for simple and rapid
      analysis. 

PMID- 27045786
TI  - Features of spectral properties of Sm(3+) complexes with dithia- and
      diselenophosphinate ligands.
AB  - The samarium complexes Sm(S2PPh2)3(THF)2 (1) and Sm(Se2PPh2)3(THF)2 (2) with soft
      donor dithia- and diselenophosphinate ligands were synthesized and their
      photophysical properties were studied in detail. Both complexes displayed the
      metal-centered photoluminescence (PL) in visible and NIR regions corresponding to
      (4)G5/2->(6)HJ (J=5/2, 7/2, 9/2, 11/2, 13/2, 15/2), (6)FJ (J=1/2, 3/2, 5/2, 7/2,
      9/2, 11/2) f-f transitions of Sm(3+). Luminescence decay curves exhibit an
      initial short build-up region and can be described by double or triple
      exponential function owing to multiphonon relaxation from the (4)F3/2 energy
      level to the (4)G5/2 one and reversible energy transfer from the Sm(3+) excited
      states to the triplet ((3)T1) state of phosphinate ligand. A Judd-Ofelt analysis
      was performed to estimate PL quantum efficiency (QE), branching ratios (beta) and
      induced-emission cross section (sigmaem) of the compounds obtained. It was found
      that the Judd-Ofelt parameter Omega2 of 1 is significantly greater than that of
      2. This feature is responsible for large values of beta (50.98%) and sigmaem
      (4.29*10(-21)cm(2)) which suggest 1 as a good candidate for the development of
      samarium doped polymethylmethacrylate (PMMA) laser medium acting on the (4)G5/2
      >(6)H9/2 transition at 645nm. The estimated room-temperature PL QE of 1 and 2
      equals to 1.9 and 0.17%, respectively. 

PMID- 27045787
TI  - Analysis of clay smoking pipes from archeological sites in the region of the
      Guanabara Bay (Rio de Janeiro, Brazil) by FT-IR.
AB  - In this study, twenty samples of clay smoking pipes excavated in an 18km(2) area
      between the Macacu and Caceribu rivers, in the municipality of Itaborai, Rio de
      Janeiro, Brazil were analyzed by FT-IR technique. The samples, excavated in
      different archeological sites of the region, are dated between the seventeenth
      and the nineteenth centuries and are part of the material culture left by
      Africans and African descendants that lived in the complex. FT-IR analyses and
      complementary SEM-EDS studies showed that the clay paste used in the manufacture
      of smoking pipes, mostly handcrafted, is composed of quartz, feldspar,
      phyllosilicates and iron oxides. Multivariate statistical tests (PCA) were
      applied to FT-IR data to assess the interactions between the archeological sites.
      The results indicated that one archeological site - Macacu IV - is greatly
      related to the other sites. The results obtained have helped archeologists and
      anthropologists in better understanding the manufacturing process employed in
      ancient ceramic artifacts produced during the period of colonial Brazil. 

PMID- 27045788
TI  - An eco-friendly stability-indicating spectrofluorimetric method for the
      determination of two anticancer stereoisomer drugs in their pharmaceutical
      preparations following micellar enhancement: Application to kinetic degradation
      studies.
AB  - A new rapid and highly sensitive stability-indicating spectrofluorimetric method
      was developed for the determination of two stereoisomers anticancer drugs,
      doxorubicin (DOX) and epirubicin (EPI) in pure form and in pharmaceutical
      preparations. The fluorescence spectral behavior of DOX and EPI in a sodium
      dodecyl sulfate (SDS) micellar system was investigated. It was found that the
      fluorescence intensity of DOX and EPI in an aqueous solution of phosphate buffer
      pH4.0 and in the presence of SDS was greatly (about two fold) enhanced and the
      mechanism of fluorescence enhancement effect of SDS on DOX was also investigated.
      The fluorescence intensity of DOX or EPI was measured at 553nm after excitation
      at 497nm. The plots of fluorescence intensity versus concentration were
      rectilinear over a range of 0.03-2MUg/mL for both DOX and EPI with good
      correlation coefficient (r>0.999). High sensitivity to DOX and EPI was attained
      using the proposed method with limits of detection of 10 and 9ng/mL and limits of
      quantitation of 29 and 28ng/mL, for DOX and EPI, respectively. The method was
      successfully applied for the determination of DOX and EPI in biological fluids
      and in their commercial pharmaceutical preparations and the results were
      concordant with those obtained using a previously reported method. The
      application of the proposed method was extended to stability studies of DOX
      following different forced degradation conditions (acidic, alkaline, oxidative
      and photolytic) according to ICH guidelines. Moreover, the kinetics of the
      alkaline and oxidative degradation of DOX was investigated and the apparent first
      order rate constants and half-life times were calculated. 

PMID- 27045789
TI  - Correction: No Acute Effect of Reduced-exertion High-intensity Interval Training
      (REHIT) on Insulin Sensitivity.

PMID- 27045790
TI  - Monoclinic Tungsten Oxide with {100} Facet Orientation and Tuned Electronic Band
      Structure for Enhanced Photocatalytic Oxidations.
AB  - Exploring surface-exposed highly active crystal facets for photocatalytic
      oxidations is promising in utilizing monoclinic WO3 semiconductor. However, the
      previously reported highly active facets for monoclinic WO3 were mainly toward
      enhancing photocatalytic reductions. Here we report that the WO3 with {100} facet
      orientation and tuned surface electronic band structure can effectively enhance
      photocatalytic oxidation properties. The {100} faceted WO3 single crystals are
      synthesized via a facile hydrothermal method. The UV-visible diffuse reflectance,
      X-ray photoelectron spectroscopy valence band spectra, and photoelectrochemical
      measurements suggest that the {100} faceted WO3 has a much higher energy level of
      valence band maximum compared with the normal WO3 crystals without preferred
      orientation of the crystal face. The density functional theory calculations
      reveal that the shift of O 2p and W 5d states in {100} face induce a unique band
      structure. In comparison with the normal WO3, the {100} faceted WO3 exhibits an
      O2 evolution rate about 5.1 times in water splitting, and also shows an acetone
      evolution rate of 4.2 times as well as CO2 evolution rate of 3.8 times in gaseous
      degradation of 2-propanol. This study demonstrates an efficient crystal face
      engineering route to tune the surface electronic band structure for enhanced
      photocatalytic oxidations.

PMID- 27045791
TI  - Decreased Emotional Perception in Obesity.
AB  - BACKGROUND: There is hardly any empirical evidence on emotion processing by
      controlled studies in obesity. MATERIAL AND METHODS: Participants rated their
      emotions in response to visual emotional stimuli from the International Affective
      Picture System. Study 1 compared obese women with normal-weight controls and
      women with eating disorders. Study 2 compared obese men with normal-weight
      controls. RESULTS: Obese women had reduced emotional intensity scores for all
      basic emotions and the mixed emotion sadness-fear. Obese men had reduced scores
      for all emotions except happiness and disgust; anger showed a trend towards
      significance. The results were mainly based on ratings from non-depressed obese
      individuals. DISCUSSION: Obese men and women scored significantly lower on most
      basic and mixed emotions. Non-depressed obese subjects seem particularly
      affected. These new findings must be validated by further study, and longitudinal
      evaluation after weight loss, e.g. by bariatric surgery, will be of interest.
      Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 27045792
TI  - Expanding DP4: application to drug compounds and automation.
AB  - The DP4 parameter, which provides a confidence level for NMR assignment, has been
      widely used to help assign the structures of many stereochemically-rich
      molecules. We present an improved version of the procedure, which can be
      downloaded as Python script instead of running within a web-browser, and which
      analyses output from open-source molecular modelling programs (TINKER and NWChem)
      in addition to being able to use output from commercial packages (Schrodinger's
      Macromodel and Jaguar; Gaussian). The new open-source workflow incorporates a
      method for the automatic generation of diastereomers using InChI strings and has
      been tested on a range of new structures. This improved workflow permits the
      rapid and convenient computational elucidation of structure and relative
      stereochemistry. 

PMID- 27045793
TI  - [Not Available].

PMID- 27045794
TI  - [Severe Raynaud's syndrome treated by lumbar sympathectomy].
AB  - Avoiding exposure of extremities to cold combined with pharmacologic treatment
      usually suffice in the attempt to suppress the related symptoms of Raynaud's
      syndrome. This case report describes a severe case of Raynaud's syndrome
      affecting the lower extremities of a 16-year-old female. She was referred to a
      centre of vascular surgery with severe vasospasms of the feet. After failed
      attempts of pharmacologic treatment, a laparoscopic lumbar sympathectomy was
      performed with no complications and a slight reduction of symptoms three years
      post-surgically. 

PMID- 27045795
TI  - [Multidisciplinary and cross-sectorial treatment of patients with complex
      regional pain syndrome].
AB  - Complex regional pain syndrome (CRPS) is a complex, painful, debilitating disease
      which occurs after trauma or surgery mainly in the wrists with a variation of 5.5
      26.2 at 100,000 inhabitants in international studies. In Denmark the prevalence
      is unknown, and it is perceived that many patients with CRPS are diagnosed late
      in their illness. There is international consensus on diagnostic criteria and
      early identification. Evidence for treatment is weak, but there are good
      experiences with highly specialized multidisciplinary treatment. A national
      clinical guideline is required. 

PMID- 27045796
TI  - [Dissection of the cervical arteries].
AB  - Dissection of the cervical arteries is an important cause of stroke in young
      adults. A haematoma in the wall of the cervical vessel leads to stenosis or
      occlusion and thereby risk of stroke. The most frequent local symptoms in carotid
      artery dissection are head- and neck pain accompanied by Horner's syndrome, while
      typical symptoms in vertebral-artery dissection are pain in the back of the neck
      and head. The mural haematoma is best visualized by magnetic resonance imaging.
      Antithrombotic versus anticoagulation treatment to prevent stroke have recently
      shown to be equally effective. 

PMID- 27045797
TI  - Epigenetic Markers to Predict Conversion From Gestational Diabetes to Type 2
      Diabetes.
AB  - CONTEXT: Lifestyle factors mediate epigenetic changes that can cause chronic
      diseases. Although animal and laboratory studies link epigenetic changes to
      diabetes, epigenetic information in women with gestational diabetes (GDM) and
      type 2 diabetes is lacking. OBJECTIVE: This study sought to measure epigenetic
      markers across pregnancy and early postpartum and identify markers that could be
      used as predictors for conversion from GDM to type 2 diabetes. DESIGN: Global
      histone H3 dimethylation was measured in white blood cells at three time points:
      30 wk gestation, 8-10 wk postpartum, and 20 wk postpartum, from four groups of
      women with and without diabetes. SETTING AND PARTICIPANTS: A total of 39
      participants (six to nine in each group) were recruited including: nondiabetic
      women; women with GDM who developed postpartum type 2 diabetes; women with GDM
      without postpartum type 2 diabetes; and women with type 2 diabetes. MAIN OUTCOME
      MEASURE: Percentages of dimethylation of H3 histones relative to total H3 histone
      methylation were compared between diabetic/nondiabetic groups using appropriate
      comparative statistics. RESULTS: H3K27 dimethylation was 50-60% lower at 8-10 and
      20 wk postpartum in women with GDM who developed type 2 diabetes, compared with
      nondiabetic women. H3K4 dimethylation was 75% lower at 8-10 wk postpartum in
      women with GDM who subsequently developed type 2 diabetes compared with women who
      had GDM who did not. CONCLUSIONS: The percentage of dimethylation of histones
      H3K27 and H3K4 varied with diabetic state and has the potential as a predictive
      tool to identify women who will convert from GDM to type 2 diabetes.

PMID- 27045798
TI  - MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines
      enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type
      features.
AB  - Oral cancer is of major public health problem in India. Current investigation was
      aimed to identify the specific deregulated miRNAs which are responsible for
      development of resistance phenotype through regulating their resistance related
      target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin
      resistant OSCC cell lines were developed from their parental human OSCC cell
      lines and subsequently characterised. The resistant cells exhibited enhanced
      proliferative, clonogenic capacity with significant up-regulation of P
      glycoprotein (ABCB1), c-Myc, survivin, beta-catenin and a putative cancer-stem
      like signature with increased expression of CD44, whereas the loss of E-cadherin
      signifies induced EMT phenotype. A comparative analysis of miRNA expression
      profiling in parental and cisplatin-resistant OSCC cell lines for a selected sets
      (deregulated miRNAs in head and neck cancer) revealed resistance specific
      signature. Moreover, we observed similar expression pattern for these resistance
      specific signature miRNAs in neoadjuvant chemotherapy treated and recurrent
      tumours compared to those with newly diagnosed primary tumours in patients with
      OSCC. All these results revealed that these miRNAs play an important role in the
      development of cisplatin-resistance mainly through modulating cancer stem-cell
      like and EMT-type properties in OSCC. 

PMID- 27045799
TI  - Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its
      histone recognition.
AB  - UHRF1 is an important epigenetic regulator for maintenance DNA methylation. UHRF1
      recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9
      (H3K9me3), but the regulatory mechanism remains unknown. Here we show that UHRF1
      adopts a closed conformation, in which a C-terminal region (Spacer) binds to the
      tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and
      RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits
      H3R2 recognition. Hm-DNA impairs the intramolecular interactions and promotes
      H3K9me3 recognition by TTD-PHD. The Spacer also facilitates UHRF1-DNMT1
      interaction and enhances hm-DNA-binding affinity of the SRA. When TTD-PHD binds
      to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm
      DNA or recruits DNMT1 to chromatin. Our study reveals the mechanism for
      regulation of H3K9me3 and hm-DNA recognition by URHF1. 

PMID- 27045800
TI  - Effects of antibody, drug and linker on the preclinical and clinical toxicities
      of antibody-drug conjugates.
AB  - Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics.
      Their design involves a tumor-specific antibody, a linker and a cytotoxic
      payload. They were designed to allow specific targeting of highly potent
      cytotoxic agents to tumor cells whilst sparing normal cells. Frequent toxicities
      that may be driven by any of the components of an ADC have been reported. There
      are currently more than 50 ADCs in active clinical development, and a further ~20
      that have been discontinued. For this review, the reported toxicities of ADCs
      were analysed, and the mechanisms for their effects are explored in detail.
      Methods to reduce toxicities, including dosing strategies and drug design, are
      discussed. The toxicities reported for active and discontinued drugs are
      important to drive the rational design and improve the therapeutic index of ADCs
      of the future.

PMID- 27045801
TI  - Total esterase activity in human saliva: Validation of an automated assay,
      characterization and behaviour after physical stress.
AB  - Although saliva has esterase activity, this activity has not been characterized
      or studied in individuals subjected to physical stress. The aim of this report
      was to develop and validate an automated spectrophotometric assay for total
      esterase activity measurement in human saliva, as well as to study the
      contribution of different enzymes on this activity and its behaviour under
      physical stress in healthy subjects. The assay used 4-nitrophenyl acetate as
      substrate and was precise, accurate and provided low limits of detection and
      quantification. Inhibition with diisopropylfluorophosphate showed that
      cholinesterase, carboxylesterase and cholesterol esterase contributions not
      represented more than 20% of total esterase. Addition of standards of lipase and
      albumin to saliva samples showed that both proteins significantly contributed to
      esterase activity only when equal or higher than 11.6 IU/L and 250 MUg/mL,
      respectively. Western blot analyses showed absence of paraoxonase-1 and high
      amount of carbonic anhydrase-VI. The high affinity of purified carbonic anhydrase
      VI for the substrate supported a major contribution of this enzyme. Total
      esterase activity and alpha-amylase was measured in saliva samples from 12
      healthy male students before and after participation in an indoor football match.
      The activity significantly increased after match and positively correlated with
      salivary alpha-amylase. This method could be used as a biomarker of physical
      stress in humans, with carbonic anhydrase-VI being the esterase that contributed
      more to the activity of the assay. 

PMID- 27045802
TI  - Oxytocin in hypothalamic supraoptic nucleus is transferred to the caudate nucleus
      to influence pain modulation.
AB  - Oxytocin (OXT), which is synthesized and secreted in the hypothalamic supraoptic
      nucleus (SON), is the most important bioactive substance in SON regulating pain
      process. Our previous study has pointed that OXT in the caudate nucleus (CdN)
      plays a role in pain modulation. The communication was designed to investigate
      the source of OXT in the rat CdN during pain process using the methods of push
      pull perfusion and radioimmunoassay. The results showed that (1) pain stimulation
      increased the OXT concentration in the CdN perfusion liquid; (2) SON
      cauterization inhibited the increase of OXT concentration in CdN perfusion liquid
      induced by the pain stimulation, which role in both sides of SON cauterization
      was stronger than that in one side of SON cauterization; and (3) SON
      microinjection of l-glutamate sodium, which excited the SON neurons, increased
      OXT concentration in the CdN perfusion liquid. The data suggested that OXT in the
      CdN was influenced by SON during pain process, i.e., OXT in the SON might be
      transferred to the CdN to influence pain modulation. 

PMID- 27045803
TI  - Propofol administration improves neurological function associated with inhibition
      of pro-inflammatory cytokines in adult rats after traumatic brain injury.
AB  - BACKGROUND: Neurological deficits following traumatic brain injury (TBI) result
      in dramatic impacts on the survivors, but the effect of propofol and associated
      mechanism are waiting to be determined. METHODS: Adult male Sprague-Dawley rats
      were randomly assigned into Sham, TBI, TBI+Intralipid and TBI+Propofol group.
      Modified Feeney method was adopted to generate TBI model from free hammer fall
      injury, and animals in TBI+Propofol group were immediately treated with propofol
      administration for 2hours after TBI, rats after TBI without propofol treatment
      was used as injury control, intralipid as vehicle in propofol was injected in
      TBI+intralipid group. Then, neurological severity scores (NSS) were evaluated at
      1, 3, 7 and 14days. Moreover, the expressions of IL-1beta, IL-6 and TNF-alpha
      mRNA and protein were examined using quantitative real time-polymerase chain
      reaction and Western blot, immunohistochemical staining was used to localize
      cytokines. RESULTS: The NSS increased greatly in the rats induced by TBI, while
      propofol could effectively decreased NSS, confirming the neuroprotective effect
      of propofol. Moreover, the mRNA expressions of IL-1beta, IL-6 and TNF-alpha, at
      1, 3, 7days after operation (dpo), were significantly augmented in the injured
      cortex, compared with sham one. But there was no difference between TBI and
      TBI+Intralipid group, but markedly decreased after propofol treatment.
      Additionally, the protein level of IL-1beta, IL-6 and TNF-alpha in four groups
      determined by Western blot and immunohistochemistry showed the similar change
      with mRNA expression. CONCLUSION: Propofol treatment could elicit a robust
      neuroprotective response, resulting in significant neurological function
      improvement for TBI rats, which was independent with intralipid. The underlying
      molecular mechanism may be partially associated with an inhibition of pro
      inflammatory cytokines.

PMID- 27045804
TI  - Pyrosequencing analysis of bacterial communities in Lake Bosten, a large brackish
      inland lake in the arid northwest of China.
AB  - The bacteria inhabiting brackish lake environments are poorly known, and there
      are few studies on the microbial diversity of these environments. Lake Bosten, a
      large brackish inland lake, is the largest lake in Xinjiang Province in
      northwestern China. Because sediments record past limnic changes, the analysis of
      sedimentary bacteria in Lake Bosten may help elucidate bacterial responses to
      environmental change. We employed 454 pyrosequencing to investigate the diversity
      and bacterial community composition in Lake Bosten. A total of 48 230 high
      quality sequence reads with 16 314 operational taxonomic units were successfully
      obtained from the 4 selected samples, and they were numerically dominated by
      members of the Deltaproteobacteria (17.1%), Chloroflexi (16.1%),
      Betaproteobacteria (12.6%), Bacteroidetes (6.6%), and Firmicutes (5.7%) groups,
      accounting for more than 58.1% of the bacterial sequences. The sediment bacterial
      communities and diversity were consistently different along the 2 geographic
      environmental gradients: (i) freshwater-brackish water gradient and (ii)
      oligotrophic-mesotrophic habitat gradient. Deltaproteobacteria, Chloroflexi, and
      Betaproteobacteria were amplified throughout all of the sampling sites. More
      Bacteroidetes and Firmicutes were found near the Kaidu River estuary (site 14).
      Our investigation showed that Proteobacteria did not display any systematic
      change along the salinity gradient, and numerous 16S rRNA sequences could not be
      identified at the genus level. Our data will provide a better understanding of
      the diversity and distribution of bacteria in arid region brackish lakes. 

PMID- 27045805
TI  - Mechanistically linked serum miRNAs distinguish between drug induced and fatty
      liver disease of different grades.
AB  - Hepatic steatosis is characterised by excessive triglyceride accumulation in the
      form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS)
      and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct
      molecular circuits of microRNA/LD-associated target genes and searched for
      mechanistically linked serum and tissue biomarkers that would distinguish between
      DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole
      genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting
      77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human
      NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N =
      167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being
      mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly
      regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH
      serum regulated miRNAs informed on hepatic inflammation, adipocytokine and
      insulin signalling, ER-and caveolae associated activities and altered
      glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis
      specifically highlighted activity of FOXO1&HNF4alpha on CPT2, the lipid droplet
      and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed
      on the molecular pathophysiology of NAFLD and permitted differentiation between
      DIS and NAFLD of different grades. 

PMID- 27045806
TI  - Discovery of piRNAs Pathway Associated with Early-Stage Spermatogenesis in
      Chicken.
AB  - Piwi-interacting RNAs (piRNAs) play a key role in spermatogenesis. Here, we
      describe the piRNAs profiling of primordial germ cells (PGCs), spermatogonial
      stem cells (SSCs), and the spermatogonium (Sp) during early-stage spermatogenesis
      in chicken. We obtained 31,361,989 reads from PGCs, 31,757,666 reads from SSCs,
      and 46,448,327 reads from Sp cells. The length distribution of piRNAs in the
      three samples showed peaks at 33 nt. The resulting genes were subsequently
      annotated against the Gene Ontology (GO) database. Five genes (RPL7A, HSPA8,
      Pum1, CPXM2, and PRKCA) were found to be involved in cellular processes.
      Interactive pathway analysis (IPA) further revealed three important pathways in
      early-stage spermatogenesis including the FGF, Wnt, and EGF receptor signaling
      pathways. The gene Pum1 was found to promote germline stem cell proliferation,
      but it also plays a role in spermatogenesis. In conclusion, we revealed
      characteristics of piRNAs during early spermatogonial development in chicken and
      provided the basis for future research. 

PMID- 27045807
TI  - Female genital mutilation: Survey of paediatricians' knowledge, attitudes and
      practice.
AB  - The study objective was to determine paediatricians' experience with female
      genital mutilation (FGM) in Australian children and adolescents. A cross
      sectional, pilot-tested national survey of paediatricians practising in Australia
      and contributing to the Australian Paediatric Surveillance Unit was conducted.
      Clinicians' knowledge, attitudes and clinical experience with FGM, awareness of
      clinical guidelines and education/training needs were recorded. Of 1311
      paediatricians surveyed, 497 (38%) responded. Fifty-seven percent were aged 50
      years or more, and 51.3% were males. Over half believed that FGM was performed in
      children in Australia and most were aware of its complications, but few asked
      about or examined for FGM. Fifty (10.3%) had seen at least one case of FGM in
      girls aged <18 years during their clinical career, including 16 (3.3%) in the
      past 5 years. Most were aware that FGM is illegal in Australia (93.9%), agreed
      all types of FGM were harmful (97.4%) and agreed that FGM violated human rights
      (98.2%). Most (87.6%) perceived FGM as a traditional cultural practice, although
      11.6% thought it was required by religion. The majority (81.8%) knew notification
      of FGM to child protection authorities was mandatory. Over half (62.0%) were
      aware of the WHO Statement on FGM, but only 22.0% knew the WHO classification of
      FGM. These novel data indicate a minority of paediatricians in Australia have
      clinical experience with or education about FGM. Educational programs, best
      practice clinical guidelines and policies are required to address knowledge gaps
      and help paediatricians identify, manage and prevent FGM in children.

PMID- 27045808
TI  - Molecular Markers of Secondary Organic Aerosol in Mumbai, India.
AB  - Biogenic secondary organic aerosols (SOA) are generally considered to be more
      abundant in summer than in winter. Here, polar organic marker compounds in urban
      background aerosols from Mumbai were measured using gas chromatography-mass
      spectrometry. Surprisingly, we found that concentrations of biogenic SOA tracers
      at Mumbai were several times lower in summer (8-14 June 2006; wet season; n = 14)
      than in winter (13-18 February 2007; dry season; n = 10). Although samples from
      less than 10% of the season are extrapolated to the full season, such seasonality
      may be explained by the predominance of the southwest summer monsoon, which
      brings clean marine air masses to Mumbai. While heavy rains are an important
      contributor to aerosol removal during the monsoon season, meteorological data
      (relative humidity and T) suggest no heavy rains occurred during our sampling
      period. However, in winter, high levels of SOA and their day/night differences
      suggest significant contributions of continental aerosols through long-range
      transport together with local sources. The winter/summer pattern of SOA loadings
      was further supported by results from chemical transport models (NAQPMS and GEOS
      Chem). Furthermore, our study suggests that monoterpene- and sesquiterpene
      derived secondary organic carbon (SOC) were more significant than those of
      isoprene- and toluene-SOC at Mumbai.

PMID- 27045809
TI  - Role of regional anaesthesia in disaster medicine: field hospital experience
      after the 2015 Nepal Earthquake.

PMID- 27045810
TI  - Perioperative medicine and mortality after elective and emergency surgery.

PMID- 27045811
TI  - Quality of Life in Women Undergoing Breast Irradiation in a Randomized,
      Controlled Clinical Trial Evaluating Different Tumor Bed Boost Fractionations.
AB  - PURPOSE: To identify differences in breast cancer patient-reported quality of
      life (QOL) between 2 radiation tumor bed boost dose regimens. METHODS AND
      MATERIALS: Four hundred patients with stage 0, I, or II breast cancer who
      underwent segmental mastectomy with sentinel node biopsy and/or axillary node
      dissection were treated with either a daily or weekly boost. Patients were
      treated prone to 40.5 Gy/15 fractions to the whole breast, 5 days per week.
      Patients were randomized to a concomitant daily boost to the tumor bed of 0.5 Gy,
      or a weekly boost of 2 Gy on Friday. Patients completed 6 validated QOL survey
      instruments at baseline, last week of treatment (3 weeks), 45-60 days from the
      completion of radiation treatment, and at 2-year follow-up. RESULTS: There were
      no statistically significance differences in responses to the 6 QOL instruments
      between the daily and weekly radiation boost regimens, even after adjustment for
      important covariates. However, several changes in responses over time occurred in
      both arms, including worsening functional status, cosmetic status, and breast
      specific pain at the end of treatment as compared with before and 45 to 60 days
      after the conclusion of treatment. CONCLUSIONS: Whole-breast, prone intensity
      modulated radiation has similar outcomes in QOL measures whether given with a
      daily or weekly boost. This trial has generated the foundation for a current
      study of weekly versus daily radiation boost in women with early breast cancer in
      which 3-dimensional conformal radiation is allowed as a prospective
      stratification factor.

PMID- 27045812
TI  - Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the
      Ubiquitin-Proteasome System.
AB  - PURPOSE: To investigate the molecular changes underlying the pathogenesis of
      radiation-induced skin fibrosis. METHODS AND MATERIALS: Rat skin was irradiated
      to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and
      adjacent normal tissues was quantified by label-free protein quantitation. Human
      skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome
      activity was determined with a fluorescent probe. The effect of proteasome
      inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by
      Western blot and immunofluorescence. The efficacy of bortezomib in wound healing
      of rat skin was assessed by the skin injury scale. RESULTS: We found that
      irradiation induced epidermal and dermal hyperplasia in rat and human skin. One
      hundred ninety-six preferentially expressed and 80 unique proteins in the
      irradiated fibrotic skin were identified. Through bioinformatic analysis, the
      ubiquitin-proteasome pathway showed a significant fold change and was
      investigated in greater detail. In vitro experiments demonstrated that
      irradiation resulted in a decline in the activity of the proteasome in human skin
      cells. The proteasome inhibitor bortezomib suppressed profibrotic TGF-beta
      downstream signaling but not TGF-beta secretion stimulated by irradiation in
      HaCaT and WS-1 cells. Moreover, bortezomib ameliorated radiation-induced skin
      injury and attenuated epidermal hyperplasia. CONCLUSION: Our findings illustrate
      the molecular changes during radiation-induced skin fibrosis and suggest that
      targeting the ubiquitin-proteasome system would be an effective countermeasure.

PMID- 27045813
TI  - Review: the effect of polymethylmethacrylate dialysis membranes on uraemic
      pruritus.

PMID- 27045814
TI  - A Collaborative Team Teaching Model for a MSW Capstone Course.
AB  - This exploratory study was embedded in a formative process for the purposes of
      improving content delivery to an evidence-based practice class, and improving
      students' performance on a comprehensive exam. A learning and teaching model was
      utilized by faculty from a three-university collaborative graduate social work
      program to examine the extent to which course texts and assignments explicitly
      supported the process, application, and evaluation of evidence-based practices.
      The model was grounded in a collaborative culture, allowing each faculty to share
      their collective skills and knowledge across a range of practice settings as they
      revised the course curriculum. As a result, faculty found they had created a
      unique community that allowed a wider context for learning and professional
      development that translated into the classroom. Students enrolled in the revised
      course across all three universities showed improvement on the comprehensive
      exam. When faculty themselves invest in collaborative learning and teaching,
      students benefit. 

PMID- 27045815
TI  - Quantum criticality of the two-channel pseudogap Anderson model: universal
      scaling in linear and non-linear conductance.
AB  - The quantum criticality of the two-lead two-channel pseudogap Anderson impurity
      model is studied. Based on the non-crossing approximation (NCA) and numerical
      renormalization group (NRG) approaches, we calculate both the linear and
      nonlinear conductance of the model at finite temperatures with a voltage bias and
      a power-law vanishing conduction electron density of states, rhoc(omega)
      proportional |omega - MUF|(r) (0 < r < 1) near the Fermi energy MUF. At a fixed
      lead-impurity hybridization, a quantum phase transition from the two-channel
      Kondo (2CK) to the local moment (LM) phase is observed with increasing r from r =
      0 to r = rc < 1. Surprisingly, in the 2CK phase, different power-law scalings
      from the well-known [Formula: see text] or [Formula: see text] form is found.
      Moreover, novel power-law scalings in conductances at the 2CK-LM quantum critical
      point are identified. Clear distinctions are found on the critical exponents
      between linear and non-linear conductance at criticality. The implications of
      these two distinct quantum critical properties for the non-equilibrium quantum
      criticality in general are discussed.

PMID- 27045816
TI  - Ambient fine particles (PM2.5 ) attenuate collagen-induced platelet activation
      through interference of the PLCgamma2/Akt/GSK3beta signaling pathway.
AB  - AIMS: It has been proven that carbon nanoparticles or diesel exhaust particles
      stimulate platelet activation. However, the effect of fine particle matter (PM2.5
      ) on platelet activation remains unknown, which motivates this study. METHODS:
      PM2.5 samples were collected in an urban area of Zhengzhou, China. To study the
      morphological characteristics and the mass concentrations of trace elements of
      PM2.5 samples, a filed-emission scanning electron microscope, the Image-J
      software, and an inductively coupled plasma mass spectrometry were used. Washed
      human platelets or platelet-rich-plasma were used to study the effect of PM2.5 on
      platelet aggregation, P-selectin expression, or platelet signaling pathways. The
      cytotoxicity in platelets exposed to PM2.5 was evaluated by a lactate
      dehydrogenase assay kit. In addition, platelet adhesion and spreading were
      studied on collagen-coated surfaces in stable conditions. RESULTS: The filed
      emission scanning electron microscope scanning showed that PM2.5 samples varied
      in shape and size distributions. The mean equivalent spherical diameter of these
      particles was 1.97 +/- 0.04 MUm, of which 82.40% were particles with equivalent
      spherical diameters of less than 2.5 MUm. The mass concentration of Ca was higher
      than that of other elements. The other elements followed the trend of
      Al>Fe>Zn>Mg>Pb>K>Mn>Cu>Ti>Ba>As>Sr>Sn>Sb>Cd>B>Se>Mo>Ag>Ni>TI>V>Co. Furthermore,
      pretreatment of PM2.5 significantly inhibited rather than potentiated collagen
      induced platelet aggregation and P-selectin expression, whereas it had no
      significant effect on ADP-induced platelet aggregation and P-selectin expression.
      The lactate dehydrogenase analysis showed trivial cytotoxic effect of PM2.5
      exposure on platelets. Pretreatment of PM2.5 inhibited platelet adhesion on
      immobilized collagen-coated surfaces; however, it almost did not impact the
      platelet spreading. Immunoblotting analysis indicated that PM2.5 reduced collagen
      induced phosphorylation of phospholipase C gamma-2 (PLCgamma2) at Tyr759, Akt at
      Ser473, and glycogen synthase kinase 3beta (GSK3beta) at Ser9. CONCLUSIONS: PM2.5
      attenuated collagen-induced platelet aggregation, alpha-granule secretion and
      adhesion, with the potential mechanism of impairing PLCgamma2, Akt, and GSK3beta
      signaling. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 530-540, 2017.

PMID- 27045818
TI  - Relation among anti-rheumatic drug therapy, CD14(+)CD16(+) blood monocytes and
      disease activity markers (DAS28 and US7 scores) in rheumatoid arthritis: A pilot
      study.
AB  - Circulating human monocytes, a functionally and phenotypically heterogeneous
      population, are emerging as fundamental cell types in rheumatoid arthritis (RA).
      The aim of this pilot study was to assess the correlation, if any, among anti
      rheumatic drug therapy, circulating CD14(+)CD16(+) monocytes and validated
      clinical scales (e.g., DAS28 score and ultrasonography US7 score) of disease
      severity in RA. Thirty consecutive RA patients, either naive or under disease
      modifying anti-rheumatic drugs (DMARDs) or biological therapy, and 10 age-matched
      healthy volunteers, were enrolled. Monocytes were prepared from heparinized blood
      samples; surface expression of CD14 and CD16 was determined by flow cytometry. RA
      patients presented a significantly higher percentage of CD14(+)CD16(+) monocytes,
      as compared to healthy subjects. There was a good correlation between DAS28
      clinical score and the ultrasound composite score US7 (r=0.66), as well as
      between both scores and the percentage of CD14(+)CD16(+) monocytes (r=0.43 and
      0.47, respectively). Naive RA patients had the highest expression (19.2+/-3.2%)
      of CD14(+)CD16(+) monocytes and elevated DAS28 score; patients on DMARDs
      presented a 7-fold increased expression of CD14(+)CD16(+) monocytes, relatively
      to healthy volunteers (2.1+/-1.4%), and an intermediate disease severity. The RA
      patients treated with biological therapy had a low percentage of CD14(+)CD16(+)
      monocytes (5.1+/-3.6%; p<0.01 vs naive and DMARDs groups), similar to the one
      detected in healthy controls, and reduced US7 and DAS28 scores. Interestingly,
      for the same DAS28 score, monocytes isolated from RA patients on biological
      therapy had a lower CD16 expression than patients on DMARDs. Therefore,
      CD14(+)CD16(+) circulating blood monocytes may represent an appropriate biomarker
      to assess RA disease activity along with DAS28 and US7 scores. Together, these
      three parameters may represent a better indicator for evaluating therapy
      efficacy.

PMID- 27045817
TI  - RNA Quality Control as a Key to Suppressing RNA Silencing of Endogenous Genes in
      Plants.
AB  - RNA quality control of endogenous RNAs is an integral part of eukaryotic gene
      expression and often relies on exonucleolytic degradation to eliminate
      dysfunctional transcripts. In parallel, exogenous and selected endogenous RNAs
      are degraded through RNA silencing, which is a genome defense mechanism used by
      many eukaryotes. In plants, RNA silencing is triggered by the production of
      double-stranded RNAs (dsRNAs) by RNA-DEPENDENT RNA POLYMERASEs (RDRs) and
      proceeds through small interfering (si) RNA-directed, ARGONAUTE (AGO)-mediated
      cleavage of homologous transcripts. Many studies revealed that plants avert
      inappropriate posttranscriptional gene silencing of endogenous coding genes by
      using RNA surveillance mechanisms as a safeguard to protect their transcriptome
      profiles. The tug of war between RNA surveillance and RNA silencing ensures the
      appropriate partitioning of endogenous RNA substrates among these degradation
      pathways. Here we review recent advances on RNA quality control and its role in
      the suppression of RNA silencing at endogenous genes and discuss the mechanisms
      underlying the crosstalk among these pathways.

PMID- 27045821
TI  - On the Equivalence of Different Methods for Calculating Resonances: From Complex
      Gaussian Basis Set to Reflection-Free Complex Absorbing Potentials via the Smooth
      Exterior Scaling Transformation.
AB  - The work compares different methods to compute metastable states (resonances)
      using Gaussian functions. The subject is of current interest, as methods of
      computing resonances using ab initio methodologies have accumulated, and it is
      relevant to shed light on their differences and similarities. Since Gaussian
      functions are usually used in quantum chemistry, we focus on their use in the
      present. The illustrative numerical example is for a single particle problem.
      However, one can learn much from the latter on a many-particle quantum chemistry
      study. Our findings show that the calculations of molecular resonances by the use
      of complex Gaussian basis functions and by adding complex absorbing potentials to
      the original molecular Hamiltonian are closely equivalent one to another. 

PMID- 27045822
TI  - Derivation and Decoration of Nets with Trigonal-Prismatic Nodes: A Unique Route
      to Reticular Synthesis of Metal-Organic Frameworks.
AB  - Quests for advanced functionalities in metal-organic frameworks (MOFs) inevitably
      encounter increasing complexity in their tailored framework architectures,
      accompanied by heightened challenges with their geometric design. In this paper,
      we demonstrate the feasibility of rationally exploiting topological prediction as
      a blueprint for predesigned MOFs. A new triangular frusta secondary building unit
      (SBU), {Zn4(tz)3}, was bridged by three TDC(2-) fragments to initially form a
      trigonal prismatic node, {Zn8(tz)6(TDC)3} (Htz = 1H-1,2,3-triazole and H2TDC =
      2,5-thiophenedicarboxylic acid). Furthermore, the trigonal prism unit can be
      considered as a double SBU derived from triply bound triangular frusta. By
      considering theoretical derived nets for linking this trigonal-prismatic node
      with ditopic, tritopic, and tetratopic linkers, we have synthesized and
      characterized a new family of MOFs that adopt the decorated lon, jea, and xai
      nets, respectively. Pore sizes have also been successively increased within TPMOF
      n family, which facilitates heterogeneous biomimetic catalysis with Fe-porphyrin
      based TPMOF-7 as a catalyst.

PMID- 27045823
TI  - Extracting Cross-Ontology Weighted Association Rules from Gene Ontology
      Annotations.
AB  - Gene Ontology (GO) is a structured repository of concepts (GO Terms) that are
      associated to one or more gene products through a process referred to as
      annotation. The analysis of annotated data is an important opportunity for
      bioinformatics. There are different approaches of analysis, among those, the use
      of association rules (AR) which provides useful knowledge, discovering
      biologically relevant associations between terms of GO, not previously known. In
      a previous work, we introduced GO-WAR (Gene Ontology-based Weighted Association
      Rules), a methodology for extracting weighted association rules from ontology
      based annotated datasets. We here adapt the GO-WAR algorithm to mine cross
      ontology association rules, i.e., rules that involve GO terms present in the
      three sub-ontologies of GO. We conduct a deep performance evaluation of GO-WAR by
      mining publicly available GO annotated datasets, showing how GO-WAR outperforms
      current state of the art approaches. 

PMID- 27045824
TI  - Integration and Querying of Genomic and Proteomic Semantic Annotations for
      Biomedical Knowledge Extraction.
AB  - Understanding complex biological phenomena involves answering complex biomedical
      questions on multiple biomolecular information simultaneously, which are
      expressed through multiple genomic and proteomic semantic annotations scattered
      in many distributed and heterogeneous data sources; such heterogeneity and
      dispersion hamper the biologists' ability of asking global queries and performing
      global evaluations. To overcome this problem, we developed a software
      architecture to create and maintain a Genomic and Proteomic Knowledge Base
      (GPKB), which integrates several of the most relevant sources of such dispersed
      information (including Entrez Gene, UniProt, IntAct, Expasy Enzyme, GO, GOA,
      BioCyc, KEGG, Reactome, and OMIM). Our solution is general, as it uses a
      flexible, modular, and multilevel global data schema based on abstraction and
      generalization of integrated data features, and a set of automatic procedures for
      easing data integration and maintenance, also when the integrated data sources
      evolve in data content, structure, and number. These procedures also assure
      consistency, quality, and provenance tracking of all integrated data, and perform
      the semantic closure of the hierarchical relationships of the integrated
      biomedical ontologies. At http://www.bioinformatics.deib.polimi.it/GPKB/, a Web
      interface allows graphical easy composition of queries, although complex, on the
      knowledge base, supporting also semantic query expansion and comprehensive
      explorative search of the integrated data to better sustain biomedical knowledge
      extraction. 

PMID- 27045825
TI  - Ontology-Based Prediction and Prioritization of Gene Functional Annotations.
AB  - Genes and their protein products are essential molecular units of a living
      organism. The knowledge of their functions is key for the understanding of
      physiological and pathological biological processes, as well as in the
      development of new drugs and therapies. The association of a gene or protein with
      its functions, described by controlled terms of biomolecular terminologies or
      ontologies, is named gene functional annotation. Very many and valuable gene
      annotations expressed through terminologies and ontologies are available.
      Nevertheless, they might include some erroneous information, since only a subset
      of annotations are reviewed by curators. Furthermore, they are incomplete by
      definition, given the rapidly evolving pace of biomolecular knowledge. In this
      scenario, computational methods that are able to quicken the annotation curation
      process and reliably suggest new annotations are very important. Here, we first
      propose a computational pipeline that uses different semantic and machine
      learning methods to predict novel ontology-based gene functional annotations;
      then, we introduce a new semantic prioritization rule to categorize the predicted
      annotations by their likelihood of being correct. Our tests and validations
      proved the effectiveness of our pipeline and prioritization of predicted
      annotations, by selecting as most likely manifold predicted annotations that were
      later confirmed. 

PMID- 27045826
TI  - A Comparison Study for DNA Motif Modeling on Protein Binding Microarray.
AB  - Transcription factor binding sites (TFBSs) are relatively short (5-15 bp) and
      degenerate. Identifying them is a computationally challenging task. In
      particular, protein binding microarray (PBM) is a high-throughput platform that
      can measure the DNA binding preference of a protein in a comprehensive and
      unbiased manner; for instance, a typical PBM experiment can measure binding
      signal intensities of a protein to all possible DNA k-mers (k = 8~10). Since
      proteins can often bind to DNA with different binding intensities, one of the
      major challenges is to build TFBS (also known as DNA motif) models which can
      fully capture the quantitative binding affinity data. To learn DNA motif models
      from the non-convex objective function landscape, several optimization methods
      are compared and applied to the PBM motif model building problem. In particular,
      representative methods from different optimization paradigms have been chosen for
      modeling performance comparison on hundreds of PBM datasets. The results suggest
      that the multimodal optimization methods are very effective for capturing the
      binding preference information from PBM data. In particular, we observe a general
      performance improvement if choosing di-nucleotide modeling over mono-nucleotide
      modeling. In addition, the models learned by the best-performing method are
      applied to two independent applications: PBM probe rotation testing and ChIP-Seq
      peak sequence prediction, demonstrating its biological applicability.

PMID- 27045827
TI  - A Low Dimensional Approximation For Competence In Bacillus Subtilis.
AB  - The behaviour of a high dimensional stochastic system described by a chemical
      master equation (CME) depends on many parameters, rendering explicit simulation
      an inefficient method for exploring the properties of such models. Capturing
      their behaviour by low-dimensional models makes analysis of system behaviour
      tractable. In this paper, we present low dimensional models for the noise-induced
      excitable dynamics in Bacillus subtilis, whereby a key protein ComK, which drives
      a complex chain of reactions leading to bacterial competence, gets expressed
      rapidly in large quantities (competent state) before subsiding to low levels of
      expression (vegetative state). These rapid reactions suggest the application of
      an adiabatic approximation of the dynamics of the regulatory model that, however,
      lead to competence durations that are incorrect by a factor of 2. We apply a
      modified version of an iterative functional procedure that faithfully
      approximates the time-course of the trajectories in terms of a two-dimensional
      model involving proteins ComK and ComS. Furthermore, in order to describe the
      bimodal bivariate marginal probability distribution obtained from the Gillespie
      simulations of the CME, we introduce a tunable multiplicative noise term in a two
      dimensional Langevin model whose stationary state is described by the time
      independent solution of the corresponding Fokker-Planck equation. 

PMID- 27045828
TI  - A Real-Time de novo DNA Sequencing Assembly Platform Based on an FPGA
      Implementation.
AB  - This paper presents an FPGA based DNA comparison platform which can be run
      concurrently with the sensing phase of DNA sequencing and shortens the overall
      time needed for de novo DNA assembly. A hybrid overlap searching algorithm is
      applied which is scalable and can deal with incremental detection of new bases.
      To handle the incomplete data set which gradually increases during sequencing
      time, all-against-all comparisons are broken down into successive window-against
      window comparison phases and executed using a novel dynamic suffix comparison
      algorithm combined with a partitioned dynamic programming method. The complete
      system has been designed to facilitate parallel processing in hardware, which
      allows real-time comparison and full scalability as well as a decrease in the
      number of computations required. A base pair comparison rate of 51.2 G/s is
      achieved when implemented on an FPGA with successful DNA comparison when using
      data sets from real genomes. 

PMID- 27045829
TI  - bLARS: An Algorithm to Infer Gene Regulatory Networks.
AB  - Inferring gene regulatory networks (GRNs) from high-throughput gene-expression
      data is an important and challenging problem in systems biology. Several existing
      algorithms formulate GRN inference as a regression problem. The available
      regression based algorithms are based on the assumption that all regulatory
      interactions are linear. However, nonlinear transcription regulation mechanisms
      are common in biology. In this work, we propose a new regression based method
      named bLARS that permits a variety of regulatory interactions from a predefined
      but otherwise arbitrary family of functions. On three DREAM benchmark datasets,
      namely gene expression data from E. coli, Yeast, and a synthetic data set, bLARS
      outperforms state-of-the-art algorithms in the terms of the overall score. On the
      individual networks, bLARS offers the best performance among currently available
      similar algorithms, namely algorithms that do not use perturbation information
      and are not meta-algorithms. Moreover, the presented approach can also be
      utilized for general feature selection problems in domains other than biology,
      provided they are of a similar structure. 

PMID- 27045830
TI  - Fast Sampling-Based Whole-Genome Haplotype Block Recognition.
AB  - Scaling linkage disequilibrium (LD) based haplotype block recognition to the
      entire human genome has always been a challenge. The best-known algorithm has
      quadratic runtime complexity and, even when sophisticated search space pruning is
      applied, still requires several days of computations. Here, we propose a novel
      sampling-based algorithm, called S-MIG (++), where the main idea is to estimate
      the area that most likely contains all haplotype blocks by sampling a very small
      number of SNP pairs. A subsequent refinement step computes the exact blocks by
      considering only the SNP pairs within the estimated area. This approach
      significantly reduces the number of computed LD statistics, making the
      recognition of haplotype blocks very fast. We theoretically and empirically prove
      that the area containing all haplotype blocks can be estimated with a very high
      degree of certainty. Through experiments on the 243,080 SNPs on chromosome 20
      from the 1,000 Genomes Project, we compared our previous algorithm MIG (++) with
      the new S-MIG (++) and observed a runtime reduction from 2.8 weeks to 34.8 hours.
      In a parallelized version of the S-MIG (++) algorithm using 32 parallel
      processes, the runtime was further reduced to 5.1 hours. 

PMID- 27045831
TI  - FocusALL: Focal Stacking of Microscopic Images Using Modified Harris Corner
      Response Measure.
AB  - Automated image analysis of microscopic images such as protein crystallization
      images and cellular images is one of the important research areas. If objects in
      a scene appear at different depths with respect to the camera's focal point,
      objects outside the depth of field usually appear blurred. Therefore, scientists
      capture a collection of images with different depths of field. Focal stacking is
      a technique of creating a single focused image from a stack of images collected
      with different depths of field. In this paper, we introduce a novel focal
      stacking technique, FocusALL, which is based on our modified Harris Corner
      Response Measure. We also propose enhanced FocusALL for application on images
      collected under high resolution and varying illumination. FocusALL resolves
      problems related to the assumption that focus regions have high contrast and high
      intensity. Especially, FocusALL generates sharper boundaries around protein
      crystal regions and good in focus images for high resolution images in reasonable
      time. FocusALL outperforms other methods on protein crystallization images and
      performs comparably well on other datasets such as retinal epithelial images and
      simulated datasets. 

PMID- 27045832
TI  - Measuring Cluster Stability in a Large Scale Phylogenetic Analysis of Functional
      Genes in Metagenomes Using pplacer.
AB  - Analysis of metagenomic sequence data requires a multi-stage workflow. The
      results of each intermediate step possess an inherent uncertainty and potentially
      impact the as-yet-unmeasured statistical significance of downstream analyses.
      Here, we describe our phylogenetic analysis pipeline which uses the pplacer
      program to place many shotgun sequences corresponding to a single functional gene
      onto a fixed phylogenetic tree. We then use the squash clustering method to
      compare multiple samples with respect to that gene. We approximate the
      statistical significance of each gene's clustering result by measuring its
      cluster stability, the consistency of that clustering result when the
      probabilistic placements made by pplacer are systematically reassigned and then
      clustered again, as measured by the adjusted Rand Index. We find that among the
      genes investigated, the majority of analyses are stable, based on the average
      adjusted Rand Index. We investigated properties of each gene that may explain
      less stable results. These genes tended to have less convex reference trees, less
      total reads recruited to the gene, and a greater Expected Distance between
      Placement Locations as given by pplacer when examined in aggregate. However, for
      an individual functional gene, these measures alone do not predict cluster
      stability. 

PMID- 27045833
TI  - Process Simulation of Complex Biological Pathways in Physical Reactive Space and
      Reformulated for Massively Parallel Computing Platforms.
AB  - Biological systems encompass complexity that far surpasses many artificial
      systems. Modeling and simulation of large and complex biochemical pathways is a
      computationally intensive challenge. Traditional tools, such as ordinary
      differential equations, partial differential equations, stochastic master
      equations, and Gillespie type methods, are all limited either by their modeling
      fidelity or computational efficiency or both. In this work, we present a scalable
      computational framework based on modeling biochemical reactions in explicit 3D
      space, that is suitable for studying the behavior of large and complex biological
      pathways. The framework is designed to exploit parallelism and scalability
      offered by commodity massively parallel processors such as the graphics
      processing units (GPUs) and other parallel computing platforms. The reaction
      modeling in 3D space is aimed at enhancing the realism of the model compared to
      traditional modeling tools and framework. We introduce the Parallel Select
      algorithm that is key to breaking the sequential bottleneck limiting the
      performance of most other tools designed to study biochemical interactions. The
      algorithm is designed to be computationally tractable, handle hundreds of
      interacting chemical species and millions of independent agents by considering
      all-particle interactions within the system. We also present an implementation of
      the framework on the popular graphics processing units and apply it to the
      simulation study of JAK-STAT Signal Transduction Pathway. The computational
      framework will offer a deeper insight into various biological processes within
      the cell and help us observe key events as they unfold in space and time. This
      will advance the current state-of-the-art in simulation study of large scale
      biological systems and also enable the realistic simulation study of macro
      biological cultures, where inter-cellular interactions are prevalent. 

PMID- 27045834
TI  - Using Formal Concept Analysis to Identify Negative Correlations in Gene
      Expression Data.
AB  - Recently, many biological studies reported that two groups of genes tend to show
      negatively correlated or opposite expression tendency in many biological
      processes or pathways. The negative correlation between genes may imply an
      important biological mechanism. In this study, we proposed a FCA-based negative
      correlation algorithm (NCFCA) that can effectively identify opposite expression
      tendency between two gene groups in gene expression data. After applying it to
      expression data of cell cycle-regulated genes in yeast, we found that six
      minichromosome maintenance family genes showed the opposite changing tendency
      with eight core histone family genes. Furthermore, we confirmed that the negative
      correlation expression pattern between these two families may be conserved in the
      cell cycle. Finally, we discussed the reasons underlying the negative correlation
      of six minichromosome maintenance (MCM) family genes with eight core histone
      family genes. Our results revealed that negative correlation is an important and
      potential mechanism that maintains the balance of biological systems by
      repressing some genes while inducing others. It can thus provide new
      understanding of gene expression and regulation, the causes of diseases, etc. 

PMID- 27045835
TI  - A Class-Information-Based Sparse Component Analysis Method to Identify
      Differentially Expressed Genes on RNA-Seq Data.
AB  - With the development of deep sequencing technologies, many RNA-Seq data have been
      generated. Researchers have proposed many methods based on the sparse theory to
      identify the differentially expressed genes from these data. In order to improve
      the performance of sparse principal component analysis, in this paper, we propose
      a novel class-information-based sparse component analysis (CISCA) method which
      introduces the class information via a total scatter matrix. First, CISCA
      normalizes the RNA-Seq data by using a Poisson model to obtain their differential
      sections. Second, the total scatter matrix is gotten by combining the between
      class and within-class scatter matrices. Third, we decompose the total scatter
      matrix by using singular value decomposition and construct a new data matrix by
      using singular values and left singular vectors. Then, aiming at obtaining sparse
      components, CISCA decomposes the constructed data matrix by solving an
      optimization problem with sparse constraints on loading vectors. Finally, the
      differentially expressed genes are identified by using the sparse loading
      vectors. The results on simulation and real RNA-Seq data demonstrate that our
      method is effective and suitable for analyzing these data. 

PMID- 27045836
TI  - New Flavonol Glucuronides from the Flower Buds of Syzygium aromaticum (Clove).
AB  - Repeated chromatography of the EtOAc-soluble fraction from the 70% EtOH extract
      of the flower buds of Syzygium aromaticum (clove) led to the isolation and
      characterization of four new flavonol glucuronides, rhamnetin-3-O-beta-d
      glucuronide (1), rhamnazin-3-O-beta-d-glucuronide (2), rhamnazin-3-O-beta-d
      glucuronide-6"-methyl ester (3), and rhamnocitrin-3-O-beta-d-glucuronide-6"
      methyl ester (4), together with 15 flavonoids (5-19) having previously known
      chemical structures. The structures of the new compounds 1-4 were determined by
      interpretation of spectroscopic data, particularly by 1D- and 2D-NMR studies. Six
      flavonoids (6, 7, 9, 14, 18, and 19) were isolated from the flower buds of S.
      aromaticum for the first time in this study. The flavonoids were examined for
      their cytotoxicity against human ovarian cancer cells (A2780) using MTT assays.
      Among the isolates, pachypodol (19) showed the most potent cytotoxicity on A2780
      cells with an IC50 value of 8.02 MUM. 

PMID- 27045837
TI  - Music appreciation and music listening in prelingual and postlingually deaf adult
      cochlear implant recipients.
AB  - OBJECTIVE: To explore the music appreciation of prelingually deaf adults using
      cochlear implants (CIs). DESIGN: Cohort study. Adult CI recipients were recruited
      based on hearing history and asked to complete the University of Canterbury Music
      Listening Questionnaire (UCMLQ) to assess each individual's music listening and
      appreciation. Results were compared to previous responses to the UCMLQ from a
      large cohort of postlingually deaf CI recipients. STUDY SAMPLE: Fifteen
      prelingually deaf and 15 postlingually deaf adult cochlear implant recipients.
      RESULTS: No significant differences were found between the prelingual and
      postlingual participants for amount of music listening or music listening
      enjoyment with their CI. Sound quality of common instruments was favourable for
      both groups, with no significant difference in the pleasantness/naturalness of
      instrument sounds between the groups. Prelingually deaf CI recipients rated
      themselves as significantly less able to follow a melody line and identify
      instrument styles compared to their postlingual peers. CONCLUSIONS: The results
      suggest that the pre- and postlingually deaf CI recipients demonstrate equivalent
      levels of music appreciation. This finding is of clinical importance, as CI
      clinicians should be actively encouraging all of their recipients to explore
      music listening as a part of their rehabilitation.

PMID- 27045838
TI  - Exploiting Complexity Information for Brain Activation Detection.
AB  - We present a complexity-based approach for the analysis of fMRI time series, in
      which sample entropy (SampEn) is introduced as a quantification of the voxel
      complexity. Under this hypothesis the voxel complexity could be modulated in
      pertinent cognitive tasks, and it changes through experimental paradigms. We
      calculate the complexity of sequential fMRI data for each voxel in two distinct
      experimental paradigms and use a nonparametric statistical strategy, the Wilcoxon
      signed rank test, to evaluate the difference in complexity between them. The
      results are compared with the well known general linear model based Statistical
      Parametric Mapping package (SPM12), where a decided difference has been observed.
      This is because SampEn method detects brain complexity changes in two experiments
      of different conditions and the data-driven method SampEn evaluates just the
      complexity of specific sequential fMRI data. Also, the larger and smaller SampEn
      values correspond to different meanings, and the neutral-blank design produces
      higher predictability than threat-neutral. Complexity information can be
      considered as a complementary method to the existing fMRI analysis strategies,
      and it may help improving the understanding of human brain functions from a
      different perspective. 

PMID- 27045839
TI  - Anti-Apoptotic Effects of Lentiviral Vector Transduction Promote Increased
      Rituximab Tolerance in Cancerous B-Cells.
AB  - Diffuse large B-cell lymphoma (DLBCL) is characterized by great genetic and
      clinical heterogeneity which complicates prognostic prediction and influences
      treatment efficacy. The most common regimen, R-CHOP, consists of a combination of
      anthracycline- and immuno-based drugs including Rituximab. It remains elusive how
      and to which extent genetic variability impacts the response and potential
      tolerance to R-CHOP. Hence, an improved understanding of mechanisms leading to
      drug tolerance in B-cells is crucial, and modelling by genetic intervention
      directly in B-cells is fundamental in such investigations. Lentivirus-based gene
      vectors are widely used gene vehicles, which in B-cells are an attractive
      alternative to potentially toxic transfection-based methodologies. Here, we
      investigate the use of VSV-G-pseudotyped lentiviral vectors in B-cells for
      exploring the impact of microRNAs on tolerance to Rituximab. Notably, we find
      that robust lentiviral transduction of cancerous B-cell lines markedly and
      specifically enhances the resistance of transduced germinal center B-cells (GCBs)
      to Rituximab. Although Rituximab works partially through complement-mediated cell
      lysis, increased tolerance is not achieved through effects of lentiviral
      transduction on cell death mediated by complement. Rather, reduced levels of
      PARP1 and persistent high levels of CD43 in Rituximab-treated GCBs demonstrate
      anti-apoptotic effects of lentiviral transduction that may interfere with the
      outcome and interpretation of Rituximab tolerance studies. Our findings stress
      that caution should be exercised exploiting lentiviral vectors in studies of
      tolerance to therapeutics in DLBCL. Importantly, however, we demonstrate the
      feasibility of using the lentiviral gene delivery platform in studies addressing
      the impact of specific microRNAs on Rituximab responsiveness. 

PMID- 27045840
TI  - Executive and Attentional Disorders, Epilepsy and Porencephalic Cyst in Autosomal
      Recessive Cerebellar Ataxia Type 3 Due to ANO10 Mutation.
AB  - BACKGROUND: ANO10 mutations have recently been reported in autosomal recessive
      cerebellar ataxia type 3 (ARCA3). The objective of this study was to describe the
      phenotype of 2 siblings with compound heterozygous ANO10 mutations and
      progressive cerebellar ataxia, epilepsy, and cognitive impairment. A
      porencephalic cyst was also described in one of them and a coenzyme Q10
      deficiency in the other one. METHODS: We performed neurological,
      neuropsychological, electromyographic, electroencephalic and MRI examinations in
      2 siblings with compound heterozygous ANO10 mutations. RESULTS: We reported for
      the first time the neuropsychological profile of 2 ARCA3 patients showing an
      adult-onset executive and attentional syndrome. Both presented epilepsy. One of
      them presented a porencephalic cyst. CONCLUSION: These results suggest that
      executive and attentional disorders are impaired in ANO10 mutation. In addition,
      epilepsy and porencephalic cysts were also described in our ARCA3 patients, the
      cyst thus expanding the clinical phenotype of ARCA3 patients due to ANO10
      mutation.

PMID- 27045841
TI  - Adolescent behavioral and neural reward sensitivity: a test of the differential
      susceptibility theory.
AB  - Little is known about the causes of individual differences in reward sensitivity.
      We investigated gene-environment interactions (GxE) on behavioral and neural
      measures of reward sensitivity, in light of the differential susceptibility
      theory. This theory states that individuals carrying plasticity gene variants
      will be more disadvantaged in negative, but more advantaged in positive
      environments. Reward responses were assessed during a monetary incentive delay
      task in 178 participants with and 265 without attention-deficit/hyperactivity
      disorder (ADHD), from N=261 families. We examined interactions between variants
      in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments
      (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers
      showed the least reward speeding when exposed to high positive peer affiliation,
      but the most when faced with low positive peer affiliation or low maternal
      warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal
      warmth on general task performance. At the neural level, DRD4 7-repeat carriers
      showed the least striatal activation during reward anticipation when exposed to
      high maternal warmth, but the most when exposed to low warmth. Findings were
      independent of ADHD severity. Our results partially confirm the differential
      susceptibility theory and indicate the importance of positive social environments
      in reward sensitivity and general task performance for persons with specific
      genotypes. 

PMID- 27045842
TI  - Preventive effects of minocycline in a neurodevelopmental two-hit model with
      relevance to schizophrenia.
AB  - Maternal immune activation can increase the vulnerability of the offspring to
      develop neuroimmune and behavioral abnormalities in response to stress in
      puberty. In offspring of immune-challenged mothers, stress-induced inflammatory
      processes precede the adult onset of multiple behavioral dysfunctions. Here, we
      explored whether an early anti-inflammatory intervention during peripubertal
      stress exposure might prevent the subsequent emergence of adult behavioral
      pathology. We used an environmental two-hit model in mice, in which prenatal
      maternal administration of the viral mimetic poly(I:C) served as the first hit,
      and exposure to sub-chronic unpredictable stress during peripubertal maturation
      as the second hit. Using this model, we examined the effectiveness of the
      tetracycline antibiotic minocycline (MINO) given during stress exposure to block
      stress-induced inflammatory responses and to prevent subsequent behavioral
      abnormalities. We found that combined exposure to prenatal immune activation and
      peripubertal stress caused significant deficits in prepulse inhibition and
      increased sensitivity to the psychotomimetic drugs amphetamine and dizocilpine in
      adulthood. MINO treatment during stress exposure prevented the emergence of these
      behavioral dysfunctions. In addition, the pharmacological intervention blocked
      hippocampal and prefrontal microglia activation and interleukin-1beta expression
      in offspring exposed to prenatal infection and peripubertal stress. Together,
      these findings demonstrate that presymptomatic MINO treatment can prevent the
      subsequent emergence of multiple behavioral abnormalities relevant to human
      neuropsychiatric disorders with onset in early adulthood, including
      schizophrenia. Our epidemiologically informed two-hit model may thus encourage
      attempts to explore the use of anti-inflammatory agents in the early course of
      brain disorders that are characterized by signs of central nervous system
      inflammation during development. 

PMID- 27045843
TI  - MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk
      pattern by psychotherapy.
AB  - Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene
      have been found to be altered in panic disorder (PD). Hypothesizing temporal
      plasticity of epigenetic processes as a mechanism of successful fear extinction,
      the present psychotherapy-epigenetic study for we believe the first time
      investigated MAOA methylation changes during the course of exposure-based
      cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between
      N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex
      matched healthy controls via direct sequencing of sodium bisulfite-treated DNA
      extracted from blood cells. MAOA methylation was furthermore analyzed at baseline
      (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a
      waiting time in healthy controls, as well as in an independent sample of female
      PD patients (N=20). Patients exhibited lower MAOA methylation than healthy
      controls (P<0.001), and baseline PD severity correlated negatively with MAOA
      methylation (P=0.01). In the discovery sample, MAOA methylation increased up to
      the level of healthy controls along with CBT response (number of panic attacks;
      T0-T1: +3.37+/-2.17%), while non-responders further decreased in methylation (
      2.00+/-1.28%; P=0.001). In the replication sample, increases in MAOA methylation
      correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The
      present results support previous evidence for MAOA hypomethylation as a PD risk
      marker and suggest reversibility of MAOA hypomethylation as a potential
      epigenetic correlate of response to CBT. The emerging notion of epigenetic
      signatures as a mechanism of action of psychotherapeutic interventions may
      promote epigenetic patterns as biomarkers of lasting extinction effects. 

PMID- 27045844
TI  - Regulation of prefrontal cortex myelination by the microbiota.
AB  - The prefrontal cortex (PFC) is a key region implicated in a range of
      neuropsychiatric disorders such as depression, schizophrenia and autism. In
      parallel, the role of the gut microbiota in contributing to these disorders is
      emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been
      instrumental in elucidating the role of the microbiota in many aspects of
      physiology, especially the role of the microbiota in anxiety-related behaviours,
      impaired social cognition and stress responsivity. Here we aim to further
      elucidate the mechanisms of the microbial influence by investigating changes in
      the homeostatic regulation of neuronal transcription of GF mice within the PFC
      using a genome-wide transcriptome profiling approach. Our results reveal a
      marked, concerted upregulation of genes linked to myelination and myelin
      plasticity. This coincided with upregulation of neural activity-induced pathways,
      potentially driving myelin plasticity. Subsequent investigation at the
      ultrastructural level demonstrated the presence of hypermyelinated axons within
      the PFC of GF mice. Notably, these changes in myelin and activity-related gene
      expression could be reversed by colonization with a conventional microbiota
      following weaning. In summary, we believe we demonstrate for the first time that
      the microbiome is necessary for appropriate and dynamic regulation of myelin
      related genes with clear implications for cortical myelination at an
      ultrastructural level. The microbiota is therefore a potential therapeutic target
      for psychiatric disorders involving dynamic myelination in the PFC. 

PMID- 27045845
TI  - Advanced brain aging: relationship with epidemiologic and genetic risk factors,
      and overlap with Alzheimer disease atrophy patterns.
AB  - We systematically compared structural imaging patterns of advanced brain aging
      (ABA) in the general-population, herein defined as significant deviation from
      typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA
      would show different patterns of structural change compared with those found in
      AD was tested via advanced pattern analysis methods. In particular, magnetic
      resonance images of 2705 participants from the Study of Health in Pomerania (aged
      20-90 years) were analyzed using an index that captures aging atrophy patterns
      (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index
      previously shown to capture atrophy patterns found in clinical AD (Spatial
      Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)).
      We studied the association between these indices and risk factors, including an
      AD polygenic risk score. Finally, we compared the ABA-associated atrophy with
      typical AD-like patterns. We observed that SPARE-BA had significant association
      with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men
      P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after
      adjusting for age. Subjects with ABA had spatially extensive gray matter loss in
      the frontal, parietal and temporal lobes (false-discovery-rate-corrected
      q<0.001). ABA patterns of atrophy were partially overlapping with, but notably
      deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD
      values; largely due to the partial spatial overlap of associated patterns in
      temporal regions. The AD polygenic risk score was significantly associated with
      SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely
      characterized by pathophysiologic mechanisms that are distinct from, or only
      partially overlapping with those of AD. 

PMID- 27045846
TI  - BDNF-Val66Met variant and adolescent stress interact to promote susceptibility to
      anorexic behavior in mice.
AB  - There is an urgent need to identify therapeutic targets for anorexia nervosa (AN)
      because current medications do not impact eating behaviors that drive AN's high
      mortality rate. A major obstacle to developing new treatments is the lack of
      animal models that recapitulate the pattern of disease onset typically observed
      in human populations. Here we describe a translational mouse model to study
      interactions between genetic, psychological and biological risk factors that
      promote anorexic behavior. We combined several factors that are consistently
      associated with increased risk of AN-adolescent females, genetic predisposition
      to anxiety imposed by the BDNF-Val66Met gene variant, social isolation stress and
      caloric restriction (CR). Approximately 40% of the mice with all of these risk
      factors will exhibit severe self-imposed dietary restriction, sometimes to the
      point of death. We systematically varied the risk factors outlined above to
      explore how they interact to influence anorexic behavior. We found that the
      Val66Met genotype markedly increases the likelihood and severity of abnormal
      feeding behavior triggered by CR, but only when CR is imposed in the peri
      pubertal period. Incidence of anorexic behavior in our model is dependent on
      juvenile exposure to social stress and can be extinguished by adolescent
      handling, but is discordant from anxiety-like behavior. Thus, this study
      characterized gene * environment interactions during adolescence that could be
      the underlying driver of abnormal eating behavior in certain AN patients, and
      represents a promising system to identify possible targets for therapeutic
      intervention. 

PMID- 27045847
TI  - Mitochondrial Genome Analysis of Wild Rice (Oryza minuta) and Its Comparison with
      Other Related Species.
AB  - Oryza minuta (Poaceae family) is a tetraploid wild relative of cultivated rice
      with a BBCC genome. O. minuta has the potential to resist against various
      pathogenic diseases such as bacterial blight (BB), white backed planthopper
      (WBPH) and brown plant hopper (BPH). Here, we sequenced and annotated the
      complete mitochondrial genome of O. minuta. The mtDNA genome is 515,022 bp,
      containing 60 protein coding genes, 31 tRNA genes and two rRNA genes. The
      mitochondrial genome organization and the gene content at the nucleotide level
      are highly similar (89%) to that of O. rufipogon. Comparison with other related
      species revealed that most of the genes with known function are conserved among
      the Poaceae members. Similarly, O. minuta mt genome shared 24 protein-coding
      genes, 15 tRNA genes and 1 ribosomal RNA gene with other rice species (indica and
      japonica). The evolutionary relationship and phylogenetic analysis revealed that
      O. minuta is more closely related to O. rufipogon than to any other related
      species. Such studies are essential to understand the evolutionary divergence
      among species and analyze common gene pools to combat risks in the current
      scenario of a changing environment. 

PMID- 27045848
TI  - Dickeyafangzhongdai sp. nov., a plant-pathogenic bacterium isolated from pear
      trees (Pyrus pyrifolia).
AB  - Gram-stain-negative, pectinolytic bacteria were repeatedly isolated from pear
      trees displaying symptoms of bleeding canker in China. Three strains, JS5T, LN1
      and QZH3, had identical 16S rRNA gene sequences that shared 99 % similarity to
      the type strain of Dickeya dadantii. Phylogenetic analysis of strains JS5T, LN1
      and QZH3 with isolates representing all species of the genus Dickeya and related
      Pectobacterium species supported their affiliation to Dickeya. Multi-locus
      sequence typing employing concatenated sequences encoding recA, fusA, gapA, purA,
      rplB, dnaX and the intergenic spacer illustrated a phylogeny which placed strains
      JS5T, LN1 and QZH3 as a distinct clade, separate from all other species of the
      genus Dickeya. Average nucleotide identity values obtained in comparison with all
      species of the genus Dickeya supported the distinctiveness of strain JS5T within
      the genus Dickeya. Additionally, all three strains were phenotypically
      distinguished from other species of the genus Dickeya by failing to hydrolyse
      casein, and by producing acids from (-)-d-arabinose, (+)melibiose, (+)raffinose,
      mannitol and myo-inositol, but not from 5-keto-d-gluconate or beta-gentiobiose.
      The name Dickeya fangzhongdai sp. nov. is proposed to accommodate these strains;
      the type strain is JS5T (=CGMCC 1.15464T=DSM 101947T). 

PMID- 27045849
TI  - The Immoral Landscape? Scientists Are Associated with Violations of Morality.
AB  - Do people think that scientists are bad people? Although surveys find that
      science is a highly respected profession, a growing discourse has emerged
      regarding how science is often judged negatively. We report ten studies (N =
      2328) that investigated morality judgments of scientists and compared those with
      judgments of various control groups, including atheists. A persistent intuitive
      association between scientists and disturbing immoral conduct emerged for
      violations of the binding moral foundations, particularly when this pertained to
      violations of purity. However, there was no association in the context of the
      individualizing moral foundations related to fairness and care. Other evidence
      found that scientists were perceived as similar to others in their concerns with
      the individualizing moral foundations of fairness and care, yet as departing for
      all of the binding foundations of loyalty, authority, and purity. Furthermore,
      participants stereotyped scientists particularly as robot-like and lacking
      emotions, as well as valuing knowledge over morality and being potentially
      dangerous. The observed intuitive immorality associations are partially due to
      these explicit stereotypes but do not correlate with any perceived atheism. We
      conclude that scientists are perceived not as inherently immoral, but as capable
      of immoral conduct. 

PMID- 27045850
TI  - Zebrafish in Brazilian Science: Scientific Production, Impact, and Collaboration.
AB  - By means of scientometric indicators, this study investigated the characteristics
      of scientific production and research collaboration involving zebrafish (Danio
      rerio) in Brazilian Science indexed by the Web of Science (WoS). Citation data
      were collected from the WoS and data regarding Impact Factor (IF) were gathered
      from journals in the Journal Citation Reports. Collaboration was evaluated
      according to coauthorship data, creating representative nets with VOSviewer.
      Zebrafish has attained remarkable importance as an experimental model organism in
      recent years and an increase in scientific production with zebrafish is observed
      in Brazil and around the world. The citation impact of the worldwide scientific
      production is superior when compared to the Brazilian scientific production.
      However, the citation impact of the Brazilian scientific production is
      consistently increasing. Brazil does not follow the international trends with
      regard to publication research fields. The state of Rio Grande do Sul has the
      greatest number of articles and the institution with the largest number of
      publications is Pontificia Universidade Catolica do Rio Grande do Sul. Journals'
      average IF is higher in Brazilian publications with international coauthorship,
      and around 90% of articles are collaborative. The Brazilian institutions
      presenting the greatest number of collaborations are Pontificia Universidade
      Catolica do Rio Grande do Sul, Universidade Federal do Rio Grande do Sul,
      Fundacao Universidade Federal de Rio Grande, and Universidade de Sao Paulo. These
      data indicate that Brazilian research using zebrafish presents a growth in terms
      of number of publications, citation impact, and collaborative work.

PMID- 27045851
TI  - How to compare cross-lagged associations in a multilevel autoregressive model.
AB  - By modeling variables over time it is possible to investigate the Granger-causal
      cross-lagged associations between variables. By comparing the standardized cross
      lagged coefficients, the relative strength of these associations can be evaluated
      in order to determine important driving forces in the dynamic system. The aim of
      this study was twofold: first, to illustrate the added value of a multilevel
      multivariate autoregressive modeling approach for investigating these
      associations over more traditional techniques; and second, to discuss how the
      coefficients of the multilevel autoregressive model should be standardized for
      comparing the strength of the cross-lagged associations. The hierarchical
      structure of multilevel multivariate autoregressive models complicates
      standardization, because subject-based statistics or group-based statistics can
      be used to standardize the coefficients, and each method may result in different
      conclusions. We argue that in order to make a meaningful comparison of the
      strength of the cross-lagged associations, the coefficients should be
      standardized within persons. We further illustrate the bivariate multilevel
      autoregressive model and the standardization of the coefficients, and we show
      that disregarding individual differences in dynamics can prove misleading, by
      means of an empirical example on experienced competence and exhaustion in persons
      diagnosed with burnout. (PsycINFO Database Record

PMID- 27045852
TI  - Effects of parceling on model selection: Parcel-allocation variability in model
      ranking.
AB  - Research interest often lies in comparing structural model specifications
      implying different relationships among latent factors. In this context parceling
      is commonly accepted, assuming the item-level measurement structure is well known
      and, conservatively, assuming items are unidimensional in the population. Under
      these assumptions, researchers compare competing structural models, each
      specified using the same parcel-level measurement model. However, little is known
      about consequences of parceling for model selection in this context-including
      whether and when model ranking could vary across alternative item-to-parcel
      allocations within-sample. This article first provides a theoretical framework
      that predicts the occurrence of parcel-allocation variability (PAV) in model
      selection index values and its consequences for PAV in ranking of competing
      structural models. These predictions are then investigated via simulation. We
      show that conditions known to manifest PAV in absolute fit of a single model may
      or may not manifest PAV in model ranking. Thus, one cannot assume that low PAV in
      absolute fit implies a lack of PAV in ranking, and vice versa. PAV in ranking is
      shown to occur under a variety of conditions, including large samples. To provide
      an empirically supported strategy for selecting a model when PAV in ranking
      exists, we draw on relationships between structural model rankings in parcel-
      versus item-solutions. This strategy employs the across-allocation modal ranking.
      We developed software tools for implementing this strategy in practice, and
      illustrate them with an example. Even if a researcher has substantive reason to
      prefer one particular allocation, investigating PAV in ranking within-sample
      still provides an informative sensitivity analysis. (PsycINFO Database Record

PMID- 27045853
TI  - Unraveling Base Stacking Driving Forces in DNA.
AB  - Base stacking is a key determinant of nucleic acid structures, but the precise
      origin of the thermodynamic driving force behind the stacking of nucleobases
      remains open. The rather mild stacking free energy measured experimentally,
      roughly a kcal/mol depending on the identity of the bases, is physiologically
      significant because while base stacking confers stability to the genome in its
      double helix form, the duplex also has to be unwound in order to be replicated or
      transcribed. A stacking free energy that is either too high or too low will over-
      or understabilize the genome, impacting the storage of genetic information and
      also its retrieval. While the molecular origin of stacking driving force has been
      attributed to many different sources including dispersion, electrostatics, and
      solvent hydrogen bonding, here we show via a systematic decomposition of the
      stacking free energy using large-scale computer simulations that the dominant
      driving force stabilizing base stacking is nonhydrophobic solvent entropy.
      Counteracting this is the conformational entropic penalty on the sugar-phosphate
      backbone against stacking, while solvent hydrogen-bonding, charge-charge
      interactions, and dispersive forces produce only secondary perturbations. Solvent
      entropic forces and DNA backbone conformational strains therefore work against
      each other, leading to a very mild composite stacking free energy in agreement
      with experiments.

PMID- 27045854
TI  - Clinical practice guidelines for the management of constipation in adults. Part
      2: Diagnosis and treatment.
AB  - Constipation is a very common disorder that adversely affects well-being and
      quality of life. Evidence-based clinical practice guidelines are an essential
      element for proper patient management and safe, effective treatment. The aim of
      these guidelines is to provide health care professionals who care for patients
      with chronic constipation with a tool that allows them to make the best decisions
      about the prevention, diagnosis and treatment of constipation. The methodology
      used to draw up these guidelines is described in the Part 1. In this article we
      will discuss the recommendations for the diagnostic and therapeutic management of
      constipation.

PMID- 27045855
TI  - The Implementation of an Evidence-Based Bundle for Bloodstream Infections in
      Neonatal Intensive Care Units in Germany: A Controlled Intervention Study to
      Improve Patient Safety.
AB  - OBJECTIVE To improve the patient safety of very-low-birthweight infants in
      neonatal departments in Germany. DESIGN Multicenter cohort study with a baseline
      (24 months), an intervention (12 months), and a postinterventional follow-up
      period (12 months) and time series analysis. STUDY POPULATION Very-low
      birthweight patients from 32 neonatal departments in Germany. METHODS Neonatal
      departments showing a standardized infection ratio of bloodstream infection 10%
      higher than the expected number (standardized infection ratio >=1.1) were invited
      to participate in the study. To reduce the occurrence of primary bloodstream
      infections, evidence-based bundles to improve catheter maintenance routines,
      insertion practice, and hand-hygiene compliance were implemented in the
      participating infirmaries. RESULTS Thirty-four departments participated in the
      study and 32 reported data. In total, 6,222 very-low-birthweight infants with
      231,868 patient-days and 1,405 cases of bloodstream infections were analyzed. In
      the baseline period the pooled mean bloodstream infection rate was 6.63 (95% CI,
      6.17-7.12) per 1,000 patient-days. The bloodstream infection rate decreased in
      the intervention period to 5.68 (relative risk, 0.86 [95% CI, 0.76-0.97]) and in
      the 1-year follow-up period to 5.31 per 1,000 patient-days (relative risk, 0.80
      [95% CI, 0.70-0.92]). The multivariable time series analysis of monthly
      aggregated data showed a significant change in the slope for the frequency of
      bloodstream infections from the start to the end of the intervention (change in
      slope incidence rate ratio, 0.97; P=.001). CONCLUSION The implementation of an
      intervention bundle is feasible and can reduce bloodstream infections in neonatal
      departments. Infect Control Hosp Epidemiol 2016;37:798-804.

PMID- 27045856
TI  - Reduced dietary protein level influences the free amino acid and gene expression
      profiles of selected amino acid transceptors in skeletal muscle of growing pigs.
AB  - This study was conducted to evaluate the effect of reduced dietary protein level
      on growth performance, muscle mass weight, free amino acids (FAA) and gene
      expression profile of selected amino acid transceptors in different fibre type of
      skeletal muscle tissues (longissimus dorsi, psoas major, biceps femoris) of
      growing pigs. A total of 18 cross-bred growing pigs (Large White * Landrace *
      Duroc) with initial body weight (9.57 +/- 0.67 kg) were assigned into three
      dietary treatments: 20% crude protein (CP) diet (normal recommended, NP), 17% CP
      diet (low protein, LP) and 14% CP diet (very low protein, VLP). The results
      indicated improved feed-to-gain ratio was obtained for pigs fed LP and NP diets
      (p < 0.01), while the pigs fed VLP diet showed the worst growth performance (p <
      0.01). There was no significant difference in the weights of longissimus dorsi
      and psoas major muscle between LP and NP groups (p > 0.05). Majority of the
      determined FAA concentration of LP group were greater than or equal to those of
      NP group in both longissimus dorsi and psoas major muscle (p < 0.01). Further,
      the mRNA expression levels of sodium-coupled neutral amino acid transceptor 2, L
      type amino acid transceptor 1 and proton-assisted amino acid transceptors 2 were
      higher in skeletal muscle tissue in LP group compared to those of the pigs fed NP
      or VLP diet. These results suggested that reduced dietary protein level (3 points
      of percentage less than recommended level) would upregulate the mRNA expression
      of amino acid transceptors to enhance the absorption of FAA in skeletal muscle of
      growing pigs. There seems to be a relationship between response of AA
      transceptors to the dietary protein level in skeletal muscle tissue of different
      fibre type. To illustrate the underlying mechanisms will be beneficial to animal
      nutrition.

PMID- 27045857
TI  - Glutamine in Alleviation of Radiation-Induced Severe Oral Mucositis: A Meta
      Analysis.
AB  - The aim of this meta-analysis was to assess the effectiveness of glutamine to
      treat severe mucositis induced by radiation therapy in patients with head and
      neck cancer. We undertook electronic searches of PubMed (1990 to January 2015),
      Embase (1990 to January 2015), and the Cochrane Library (2013, Issue 2) to
      identify relevant studies. We included randomized controlled trials of glutamine
      to alleviate oral mucositis (OM) in patients with head and neck cancer who
      received radiotherapy. Information regarding methods, patients, results, and risk
      of bias was independently extracted by two authors. Statistical analyses were
      conducted to calculate the odds ratio and 95% confidence intervals (95%CIs) using
      fixed-effect models. We identified five clinical studies that included 234
      patients with head and neck cancer. All studies were assessed as being at low
      risk of bias in most items of six domains. In this meta-analysis, glutamine
      treatment showed a statistically significant benefit with respect to reducing the
      risk and severity of OM induced by radiotherapy compared to either placebo or no
      treatment (risk ratio 0.17, 95%CI 0.06-0.47). Overall, glutamine significantly
      reduces the risk and severity of OM during radiotherapy or chemotherapy. Further
      prospective and large trials are required to support the findings.

PMID- 27045858
TI  - Correction: Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes
      Containing Drug Resistance Mutations in Antiretroviral Treatment-Naive HIV
      Infected Individuals.

PMID- 27045859
TI  - Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency
      After Pancreatic Surgery.
AB  - OBJECTIVE: To provide evidence-based recommendations for the management of
      exocrine pancreatic insufficiency (EPI) after pancreatic surgery. BACKGROUND: EPI
      is a common complication after pancreatic surgery but there is certain confusion
      about its frequency, optimal methods of diagnosis, and when and how to treat
      these patients. METHODS: Eighteen multidisciplinary reviewers performed a
      systematic review on 10 predefined questions following the GRADE methodology. Six
      external expert referees reviewed the retrieved information. Members from Spanish
      Association of Pancreatology were invited to suggest modifications and voted for
      the quantification of agreement. RESULTS: These guidelines analyze the definition
      of EPI after pancreatic surgery, (one question), its frequency after specific
      techniques and underlying disease (four questions), its clinical consequences
      (one question), diagnosis (one question), when and how to treat postsurgical EPI
      (two questions) and its impact on the quality of life (one question). Eleven
      statements answering those 10 questions were provided: one (9.1%) was rated as a
      strong recommendation according to GRADE, three (27.3%) as moderate and seven
      (63.6%) as weak. All statements had strong agreement. CONCLUSIONS: EPI is a
      frequent but under-recognized complication of pancreatic surgery. These
      guidelines provide evidence-based recommendations for the definition, diagnosis,
      and management of EPI after pancreatic surgery.

PMID- 27045860
TI  - Identification of a Novel Mycobacterial Arabinosyltransferase Activity Which Adds
      an Arabinosyl Residue to alpha-d-Mannosyl Residues.
AB  - The arabinosyltransferases responsible for the biosynthesis of the arabinan
      domains of two abundant heteropolysaccharides of the cell envelope of all
      mycobacterial species, lipoarabinomannan and arabinogalactan, are validated drug
      targets. Using a cell envelope preparation from Mycobacterium smegmatis as the
      enzyme source and di- and trimannoside synthetic acceptors, we uncovered a
      previously undetected arabinosyltransferase activity. Thin layer chromatography,
      GC/MS, and LC/MS/MS analyses of the major enzymatic product are consistent with
      the transfer of an arabinose residue to the 6 position of the terminal mannosyl
      residue at the nonreducing end of the acceptors. The newly identified enzymatic
      activity is resistant to ethambutol and could correspond to the priming
      arabinosyl transfer reaction that occurs during lipoarabinomannan biosynthesis.

PMID- 27045861
TI  - Orthogonal strategy for the synthesis of dual-functionalised beta(3)-peptide
      based hydrogels.
AB  - We have described a new class of hydrogelator based on helical beta(3)-peptides
      carrying a bioactive payload. The beta(3)-peptides self-assemble in aqueous
      solution to form a nanofibrous mesh resulting in a stable hydrogel. The simple
      design provides the versatility for attaching different functional payloads to
      the beta(3)-peptide scaffold to develop new materials. 

PMID- 27045862
TI  - Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease:
      animal and human studies.
AB  - Betatrophin/angiopoietin-like protein 8 (ANGPTL8) is a liver-secreted protein
      recently identified as a potent stimulator of beta cell proliferation in mice.
      However, it is unclear how betatrophin is regulated in humans with non-alcoholic
      fatty liver disease (NAFLD). We investigated the role of betatrophin in mice and
      in humans with and without NAFLD. Serum betatrophin levels were examined by ELISA
      in 164 subjects, including 96 patients with NAFLD. Levels were significantly
      elevated in subjects with NAFLD compared with controls (1.301 +/- 0.617 vs. 0.900
      +/- 0.574 MUg/L, P < 0.001), even after stratification by diabetic or obesity
      status. Circulating betatrophin positively correlated with obesity or glycemic
      indices, liver enzyme profiles, and NAFLD status, and was confirmed by
      multivariate regression analyses (beta = 0.195, P = 0.040). However, when
      including insulin resistance index in the model, the significant association
      between betatrophin level and NAFLD was diminished due to a mediation effect of
      insulin resistance on this relationship. Palmitate or tunicamycin increased
      betatrophin expression in HepG2 cells, while a chemical chaperone blocked its
      induction. Hepatic expression of betatrophin was elevated in mice with NAFLD
      including db/db or ob/ob mice and mice with a high-fat or methionine-choline
      deficient diet. In conclusion, circulating betatrophin was increased in mice and
      humans with NAFLD and its expression was induced by endoplasmic reticulum stress
      in hepatocytes (Clinical trial no. NCT02285218). 

PMID- 27045863
TI  - Huaier aqueous extract sensitizes cells to rapamycin and cisplatin through
      activating mTOR signaling.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has been
      increasingly used to treat cancers. Trametes robiniophila Murr. (Huaier) is a
      medicinal fungus for treatment of inflammation and cancer. Huaier Granule has
      great clinical effect in various types of cancers, including liver cancer, lung
      cancer, gastric cancer, and breast cancer. AIM OF THE STUDY: The present study
      was performed to determine the therapeutical effect of Huaier on cancers caused
      by aberrant mTOR signaling in vitro and in vivo, investigate the combination
      effect of Huaier and rapamycin or cisplatin on cell viability, and explore its
      underlying mechanism. MATERIALS AND METHODS: The therapeutical effect of Huaier
      on cancers caused by aberrant mTOR signaling and the underlying mechanism of
      combination effect of Huaier and rapamycin or cisplatin on cell viability were
      investigated in mouse embryonic fibroblasts, rat uterine leiomyoma cells, human
      hepatoma cells, human lung carcinoma cells, and xenograft tumor model by cell
      viability assay and immunoblotting. RESULTS: Activation of mTOR sensitizes cells
      to Huaier treatment. Huaier inhibits tumorigenic capacity of cells with activated
      mTOR in vivo. Moreover, activation of mTOR signaling induced by Huaier
      contributes to the increased sensitivity of cells to rapamycin or cisplatin in
      response to Huaier treatment. CONCLUSIONS: Huaier may be a potential drug for the
      treatment of cancers caused by aberrant mTOR signaling. The combination of Huaier
      and rapamycin may be a candidate regimen in the treatment of these cancers.

PMID- 27045864
TI  - A randomized, double-blind, multicenter, placebo-controlled clinical study on the
      efficacy and safety of Shenmai injection in patients with chronic heart failure.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Shenmai injection (SMI) is a traditional Chinese
      herbal medicine extracted from Panax ginseng (Panax ginseng C.A. Mey, steamed and
      dry) and Ophiopogon japonicus (Ophiopogon japonicus (L.f.) Ker-Gawl, root). It
      has been widely used for the treatment of chronic heart failure (CHF) in China.
      However, the evidence supporting its effects remains unclear due to lack of high
      quality trials. The aim of this study was to investigate the efficacy and safety
      of SMI in CHF patients with coronary artery disease (CAD). MATERIALS AND METHODS:
      This double-blind, multicenter study randomized 240 eligible patients equally to
      receive SMI or placebo (100ml/day) in addition to standard medicines for the
      treatment of CHF. The primary endpoint was the New York Heart Association (NYHA)
      functional classification. The secondary endpoints were 6-min walking distance
      (6MWD), short-form 36 (SF-36) hearth survey score, traditional Chinese medicines
      (TCM) syndrome score, left ventricular ejection fractions (LVEF) and B-type
      natriuretic peptide (BNP) level. RESULTS: During treatment of 1 week, the NYHA
      functional classification was gradually improved in both groups, but the SMI
      group demonstrated a significantly greater improvement compared with the placebo
      group (p=0.001). Moreover, the improvement in patients received SMI was superior
      to those in control group with respect to 6MWD, SF-36 score and TCM syndrome
      score. Treatment with SMI within 1 week was well tolerated with no apparent
      safety concerns. CONCLUSIONS: The integrative treatment with standard medicines
      plus SMI can further improve NYHA functional classification for patients with CHF
      and CAD. Therefore, SMI could be recommended in the combination therapy for CHF
      accompanied with CAD.

PMID- 27045865
TI  - The effective components of Huanglian Jiedu Decoction against sepsis evaluated by
      a lipid A-based affinity biosensor.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HJD), the classical
      recipe for relieving fever and toxicity, has been used for treating sepsis in
      China for sixteen years. However, the effective components of HJD have not been
      elucidated until now. Therefore, there is a need to elucidate the effective
      components of HJD against sepsis on animal models induced by endotoxin (LPS). The
      affinity force of the effective components of HJD with lipid A was evaluated by a
      biosensor. MATERIALS AND METHODS: Lipid A is regarded as the bioactive center of
      LPS and is always used as a drug target. In order to obtain the effective
      components of HJD against sepsis, seven fractions from HJD were tested by a
      biosensor method for assessing the affinity for lipid A. After further
      separation, the components were isolated from high lipid A-binding fractions and
      their affinities to lipid A were assessed with the aid of a biosensor. Their
      activities were then assayed by an in vivo experiment administered through a tail
      vein injection. The levels of LPS, TNF-alpha, and IL-6 from the blood were found
      and pathology experiments were performed. RESULTS: Three out of the seven
      fractions exhibited high lipid A-binding affinities. Berberine, baicalin and
      geniposide were obtained from the three high lipid A-binding fractions. The
      animal experiments indicated that the levels of LPS, TNF-alpha and IL-6 in the
      medicated treatment groups were much lower than that of the model group
      ((**)P<0.01). The medicated treatment groups exhibited stronger protective
      activities on varying organs in the animal model. CONCLUSIONS: Berberine,
      baicalin and geniposide could neutralize LPS by binding with lipid A and then
      reduce the release of IL-6 and TNF-alpha induced by LPS. Furthermore, berberine,
      baicalin and geniposide exhibited protective activities on varying organs
      compared to the animal model established by the LPS-induced. These results
      validate that the components from HJD neutralized LPS and then depressed the
      release of IL-6 and TNF-alpha induced by LPS. This gives further evidence that
      HJD would be a suitable treatment for sepsis and protecting vital organs.

PMID- 27045866
TI  - Testing the absorption of the extracts of Coreopsis tinctoria Nutt. in the
      intestinal canal in rats using an Ussing chamber.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Coreopsis tinctoria Nutt mainly distributed in
      Hetian region of Xinjiang at an altitude of 3000m, which is used as Uyghur
      traditional medicine because of its clearing heat, promoting circulation and
      removing toxicity and antihypertension, ect. effect. AIM OF THE STUDY: This
      research was to study the four ingredients in the extracts of Coreopsis tinctoria
      Nutt. that are absorbed in different intestinal segments in rats to lay the
      foundation for further study on the effective constituents, tissue distribution,
      metabolism, and spectrum-effect relationships of these extracts. MATERIALS AND
      METHODS: High, medium, and low concentrations were prepared according to their
      pharmacological effects. Quantitative analysis multi-components by single marker
      was used to test the cumulative absorption volume Q, absorption rate constant Ka,
      and apparent permeability coefficient Papp of the four main ingredients in C.
      tinctoria Nutt. extract in different intestinal segments in rats using a Ussing
      chamber model and high-performance liquid chromatography. RESULTS: The Papp of
      chlorogenic acid and flavanomarein in the duodenum, jejunum, ileum, and colon
      were 1.0*10(-6) to 10*10(-6)cms(-1). Papp of marein in the duodenum and jejunum
      was <1.0*10(-6), and was 1.0*10(-6) to 10*10(-6)cms(-1) in the ileum and colon.
      Papp of 3,5-O-dicaffeoylquinic acid in the duodenum was <1.0*10(-6)cms(-1), while
      it was 1.0*(1)0(-6) to 10*10(-6)cms(-1) in the jejunum, ileum, and colon.
      CONCLUSIONS: All four chemical components of the plant extract can be absorbed by
      the intestinal canal of rats, which conforms to zero-order absorption; the ileum
      presented the best absorption.

PMID- 27045867
TI  - Common Genetic Variants Influence Whorls in Fingerprint Patterns.

PMID- 27045868
TI  - Biological Characterization and in Vivo Assessment of the Activity of a New
      Synthetic Macrocyclic Antifungal Compound.
AB  - We recently identified a novel family of macrocyclic amidinoureas showing potent
      antifungal activity against Candida spp. In this study, we demonstrate the
      fungicidal effect of these compounds as well as their killing activity in a dose
      dependent manner. Transcriptional analysis data indicate that our molecules
      induce a significant change in the transcriptome involving ATP binding cassette
      (ABC) transporter genes. Notably, experiments against Candida albicans mutants
      lacking those genes showed resistance to the compound, suggesting the involvement
      of ABC transporters in the uptake or intracellular accumulation of the molecule.
      To probe the mode of action, we performed fluorescence microscopy experiments on
      fungal cells treated with an ad-hoc synthesized fluorescent derivative.
      Fluorescence microscopy images confirm the ability of the compound to cross the
      membrane and show a consistent accumulation within the cytoplasm. Finally, we
      provide data supporting the in vivo efficacy in a systemic infection murine model
      setup with a drug-resistant strain of C. albicans.

PMID- 27045869
TI  - Tracking of physical activity and fitness during the early years.
AB  - The early years are characterized by rapid physical growth and the development of
      behaviours such as physical activity. The objectives of this study were to assess
      the 12-month changes in and the tracking of physical activity and fitness in 400
      preschoolers (201 boys, 4.5 +/- 0.9 years of age). Physical activity data,
      expressed as minutes per day and as the percentage of time spent at various
      intensities while wearing an accelerometer, were collected in 3-s epochs for 7
      days. Short-term muscle power, assessed with a 10-s modified Wingate Anaerobic
      Test, was expressed as absolute (W) and relative (W/kg) peak power (PP) and mean
      power (MP). Aerobic fitness, assessed with the Bruce Protocol progressive
      treadmill test, was expressed as maximal treadmill time and heart rate recovery
      (HRR). Light physical activity decreased by 3.2 min/day (p < 0.05), whereas
      vigorous physical activity increased by 3.7 min/day (p < 0.001), from year 1 to
      year 2. Physical activity exhibited moderate tracking on the basis of Spearman
      correlations (r = 0.45-0.59, p < 0.001) and fair tracking on the basis of kappa
      statistics (kappa = 0.26-0.38). PP and MP increased from year 1 (PP, 94.1 +/-
      37.3 W; MP, 84.1 +/- 30.9 W) to year 2 (PP, 125.6 +/- 36.2 W; MP, 112.3 +/- 32.2
      W) (p < 0.001) and tracked moderately to substantially (PP, r = 0.89, kappa =
      0.61; MP, r = 0.86, kappa = 0.56). Time to exhaustion on the treadmill increased
      from 9.4 +/- 2.3 min to 11.8 +/- 2.3 min (p < 0.001) and tracked strongly (r =
      0.82, kappa = 0.56). HRR was unchanged at 65 +/- 14 beats/min (p = 0.297) and
      tracked fairly (r = 0.52, kappa = 0.23). The findings indicate that fitness
      tracks better than physical activity over a 12-month period during the early
      years. 

PMID- 27045871
TI  - Strong is the new skinny: A content analysis of fitspiration websites.
AB  - "Fitspiration" websites are media that aim to inspire people to live healthy and
      fit lifestyles through motivating images and text related to exercise and diet.
      Given the link between similar Internet content (i.e., healthy living blogs) and
      problematic messages, we hypothesized that content on these sites would over
      emphasize appearance and promote problematic messages regarding exercise and
      diet. Keywords "fitspo" and "fitspiration" were entered into search engines. The
      first 10 images and text from 51 individual websites were rated on a variety of
      characteristics. Results indicated that a majority of messages found on
      fitspiration websites focused on appearance. Other common themes included content
      promoting exercise for appearance-motivated reasons and content promoting dietary
      restraint. "Fitspiration" websites are a source of messages that reinforce over
      valuation of physical appearance, eating concerns, and excessive exercise.
      Further research is needed to examine the impact viewing such content has on
      participants' psychological health. 

PMID- 27045872
TI  - Systematic review of factors affecting driving and motor vehicle transportation
      among people with autism spectrum disorder.
AB  - PURPOSE: This systematic review is to critically appraise the literature on
      factors affecting driving and motor vehicle transportation experiences of people
      with autism spectrum disorders (ASD) and to provide insight into future
      directions for research. METHODS: Systematic searches of eight databases
      identified 22 studies meeting our inclusion criteria. These studies were analysed
      in terms of the characteristics of the participants, methodology, results of the
      study and quality of the evidence. RESULTS: Among the 22 studies, 2919
      participants (364 individuals with ASD; 2555 parents of youth with ASD; mean age
      of person with ASD = 17.3) were represented, across six countries. Studies (n =
      13) focused on factors affecting driving, including challenges in obtaining a
      licence, driving confidence, driving behaviours and strategies to improve driving
      skills. In regards to factors related to public and/or school transportation,
      nine studies explored rates of transportation use, access, cost and safety.
      CONCLUSION: Our findings highlight several gaps in the research and an urgent
      need for further transportation-related training and supports for people with
      ASD. Implications for rehabilitation Many people with ASD encounter challenges in
      obtaining a driver's licence, driving confidence and driving performance compared
      to those without ASD. Several strategies can be useful when teaching people with
      ASD to drive including direct communication, encouraging coping mechanisms,
      breaking down tasks and providing regular and consistent driving lessons.
      Clinicians and educators should advocate for further transportation-related
      training and supports for people with ASD. More research is needed from the
      perspective of people with ASD to understand their experiences and the particular
      challenges that they encounter in obtaining a licence and navigating public
      transportation.

PMID- 27045873
TI  - Status epilepticus triggers early mitochondrial fusion in the rat hippocampus in
      a lithium-pilocarpine model.
AB  - Many reports investigating the hippocampus have demonstrated an increase in
      neuronal damage, cellular loss, oxidative stress and mitochondrial DNA damage
      during status epilepticus (SE); however, information regarding alterations in
      mitochondrial fission and fusion events in SE is lacking. The aim of the present
      study was to examine the possible imbalance between mitochondrial fission and
      fusion in the hippocampus of male rats after acute seizure mediated by SE. In
      this study, we used ninety animals were randomly divided into control and SE
      groups and subjected to the lithium-pilocarpine model of epilepsy. Hippocampi
      were obtained at 3, 24 and 72h after SE, and the cytoplasmic and mitochondrial
      fractions of the cells were used to analyze changes in the Drp1 and Fis1 fission
      proteins and the Mfn1 and Opa1 fusion proteins by western blot analysis.
      Moreover, changes in the expression of fission and fusion mRNA transcripts were
      evaluated by real-time PCR. Mitochondrial morphology was also analyzed using
      standard transmission electron microscopy. Our data showed that the fission
      related mRNA Drp1 was down-regulated rapidly after SE, while Fis1 did not show
      any significant changes in expression. Moreover, the mitochondrial fusion
      associated proteins Mfn1 and Opa1 exhibited an increase in expression at 72h
      after SE. Electron microphotography revealed several morphological changes, such
      as swollen mitochondria and damage of the inner mitochondrial membrane, at 24h;
      at 72h elongation of some mitochondrial was also observed. Our results suggest
      that after the initiation of SE, the main regulator of the fission mRNA Drp1 is
      down-regulated, which in turn regulates mitochondrial fission and leads to an
      increase in the Mfn1 and Opa1 proteins to induce mitochondrial fusion, suggesting
      an imbalance of the fission and fusion processes.

PMID- 27045874
TI  - Effects of combination therapy of statin and N-acetylcysteine for the prevention
      of contrast-induced nephropathy in patients with ST-segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is a risk factor for contrast
      induced nephropathy (CIN). We investigated whether pretreatment with statin, N
      acetylcysteine (NAC) and sodium bicarbonate (NaHCO3) reduces the risk of CIN.
      METHODS: We conducted a prospective trial and enrolled a total of 334 ST-segment
      elevation myocardial infarction (STEMI) patients. Patients were divided into four
      groups: Group I (statin 40mg), Group II (statin 80mg), Group III (statin 80mg
      plus NAC 1200mg) and Group IV (regimen of group III plus NaHCO3 154mEq/L). CIN
      was defined as >=25% or >=0.5mg/dL increase in serum creatinine from the baseline
      within the 72h after PCI. RESULTS: CIN occurred in 72 (21.6%) patients. The
      incidence of CIN was the lowest in the group III (14.3%), and multivariate
      analysis showed the lower incidence of CIN in group III compared to Group I [odds
      ratio (OR) 0.29, 95% confidence interval (CI) 0.13-0.64, p=0.002]. Admission
      hyperglycemia [(AHG)>198mg/dL] (OR 2.20, 95% Cl 1.20-3.68, p=0.011) and the use
      of intra-aortic balloon pump (IABP) (OR 4.20, 95% CI 1.38-12.78, p=0.016) were
      independent predictors for CIN. The CIN (OR 9.00, 95% CI 1.30-62.06, p=0.026) was
      an independent predictor for in-hospital mortality. CONCLUSIONS: Combination of
      high-dose statin plus NAC was associated with lower incidence of CIN in patients
      with STEMI who underwent primary PCI compared to statin only.

PMID- 27045875
TI  - Apolipoprotein A5 inhibits adipogenesis of AMSCs potentially through the Cidec
      pathway.

PMID- 27045876
TI  - Metabolic syndrome and sudden cardiac death: Validity on risk assessment.

PMID- 27045877
TI  - Outcomes with bioabsorbable vascular scaffolds versus everolimus eluting stents:
      Insights from randomized trials.
AB  - BACKGROUND: Bioresorbable vascular scaffolds (BVS) have been shown to be non
      inferior to second generation drug eluting stents in recent clinical trials.
      However, the trials were not powered for individual endpoints and there is
      concern for increased device thrombosis with BVS. METHODS: We performed a
      systematic search for randomized clinical trials of BVS versus EES. Efficacy
      outcomes were target lesion revascularization (TLR) and target vessel
      revascularization (TVR). Safety outcomes were death, myocardial infarction (MI),
      and device thrombosis. Meta-regression analyses were performed to evaluate the
      association of device thrombosis with clinical characteristics (percent patients
      with acute coronary syndrome) and device deployment characteristics (percent with
      post stent balloon dilation). RESULTS: We identified six RCTs that enrolled 3738
      patients. When compared with EES, BVS was associated with similar risk of TLR
      (RR=1.06; 95% CI 0.73-1.54), TVR (RR=1.00; 95% CI 0.74-1.35), death (RR=1.11; 95%
      CI 0.53-2.33) and cardiovascular death (RR=1.39; 95% CI 0.43-4.43) but
      numerically higher MI (RR=1.35; 95% CI 0.98-1.86) and definite or probable device
      thrombosis (RR=2.11; 95% CI 0.99-4.47). In a sensitivity analysis using the Peto
      odds ratio method, the risk of definite or probable device thrombosis was
      significantly increased (OR=2.08; 95% CI 1.06-4.08; P=0.03), although this did
      not reach statistical significance in four other models. The risk of definite or
      probable device thrombosis with BVS was reduced in trials where more post stent
      balloon dilation was used and in patients without acute coronary syndrome.
      Moreover, trial sequential analysis showed that the cumulative z-curve crossed
      the conventional boundary and not the trial sequential boundary, indicating lack
      of robust data to support increased definite or probable device thrombosis with
      BVS. CONCLUSIONS: In patients with noncomplex obstructive coronary disease, BVS
      are comparable to EES for most efficacy and safety outcomes except for a
      numerical increase in device thrombosis and MI. The risk of the latter outcomes
      was mitigated in trials where more post stent balloon dilation was used and in
      patients without acute coronary syndrome. Moreover, with only 3738 patients, the
      trials are underpowered to detect a difference in rare events such as device
      thrombosis.

PMID- 27045878
TI  - Hypochloraemia as a predictor of developing hyponatraemia and poor outcome in
      acute heart failure patients.
AB  - AIMS: Heart failure (HF) is a major public health issue currently affecting more
      than 23 million patients worldwide. Hyponatraemia has been shown to be a
      predictor of poor outcome in patients with acute and chronic HF. Therefore, we
      aimed at finding a marker for early detection of patients at risk for developing
      hyponatraemia. To this end, the present study investigated the relationship
      between initial serum chloride and follow-up sodium levels in acute heart failure
      (AHF) patients. METHODS AND RESULTS: The present study was performed as a
      prospective, single-centre, observational research with a total of 152
      hospitalised AHF patients. Compared to patients with initial normochloraemia,
      patients with initial hypochloraemia had a statistically significantly higher
      incidence of hyponatraemia after a 3-month follow-up [P<0.001; odds ratio
      (OR)=27.08, CI: 4.3-170.7]. A similar finding was obtained upon exclusion of
      patients with initial hyponatraemia with Fishers test [P=0.034; odds ratio
      (OR)=15.5, CI:1.7-140.6]. Binary logistic regression revealed a significantly
      increased in-hospital mortality in the hypochloraemic/normonatriaemic (OR=4.08,
      CI 1.08-15.43, P=0.039), but not in the hypochloraemic/hyponatraemic,
      normochloraemic/hyponatraemic or normonatriaemic/normochloraemic patients.
      Ejection fraction (EF) at admission was significantly higher in
      hypochloraemic/normonatriaemic, compared to normonatriaemic/normochloraemic
      patients, but similar to EF in both hypochloraemic/hyponatraemic and
      normochloraemic/hyponatraemic patients. The N-terminal precursor Brain
      Natriuretic Peptide (Nt-proBNP) levels at admission were significantly lower in
      hypochloraemic/normonatriaemic compared to hypochloraemic/hyponatraemic and
      normonatriaemic/normochloraemic patients, respectively. CONCLUSION: The data show
      that initial low serum chloride concentration is predictive of developing
      hyponatraemia and associated with increased in-hospital mortality in AHF
      patients.

PMID- 27045879
TI  - Another side effect of ticagrelor: Atrial fibrillation.

PMID- 27045880
TI  - Favorable response to an endothelin receptor antagonist in mitomycin-induced
      pulmonary veno-occlusive disease with pulmonary capillary hemangiomatosis.

PMID- 27045881
TI  - Isolated arterial calcifications of the lower extremities: A clue for NT5E
      mutation.

PMID- 27045882
TI  - Onset factors in cerebral palsy: A systematic review.
AB  - Studies have noted several factors associated with the occurrence of Cerebral
      Palsy (CP), yet considerable uncertainty remains about modifiable factors related
      to disease onset. A systematic review was performed to identify existing
      systematic reviews and primary studies pertaining to targeted factors associated
      with the onset of CP. The following databases were searched: MEDLINE, MEDLINE In
      Process, EMBASE, PsycINFO, Scopus, Web of Science, Cochrane Database of
      Systematic Reviews, CINHAL, ProQuest Dissertations & Theses, Huge Navigator, AARP
      Ageline. Variations of MeSH and keyword search terms were used. Critical
      appraisal was conducted on selected articles. Data extraction targeted reported
      factors, risk estimates, and 95% confidence intervals (CI). Findings identified
      two systematic reviews and three meta- analyses, as well as 83 studies of case
      control, cohort, and cross-sectional methodological designs. Selected studies
      indicated that lower gestational age was associated with the onset of CP. Medical
      diagnoses for the mother, in particular chorioamnionitis, was found to be
      positively associated with onset of CP. Preeclampsia was reported to be either
      inconclusive or positively associated with CP onset. Low birth weight
      predominantly indicated a positive association with the onset of CP, while male
      gender showed mixed findings. The combination of male gender with pre-term or low
      birth weight was also found to be positively associated with CP. Evidence was
      identified in the literature pertaining to specific factors relating to the onset
      of CP, in particular showing positive associations with lower gestational age and
      low birth weight.

PMID- 27045883
TI  - Factors associated with onset, relapses or progression in multiple sclerosis: A
      systematic review.
AB  - Multiple sclerosis (MS) is a chronic disease of the central nervous system with
      an unidentified etiology. We systematically reviewed the literature on the
      possible risk factors associated with MS disease onset, relapses and progression
      from 1960 to 2012 by accessing six databases and including relevant systematic
      reviews, meta-analyses, case-control or cohort studies. The focus was on
      identifying modifiable risk factors. Fifteen systematic reviews and 169 original
      articles were quality assessed and integrated into a descriptive review. Best
      evidence, which included one or more prospective studies, suggested that lower
      exposure to sunlight and/or lower serum vitamin D levels were associated with an
      increased risk of developing MS onset and subsequent relapses, but a similar
      quality of evidence was lacking for disease progression. Prospective studies
      indicated that cigarette smoking may increase the risk of MS as well as
      accelerate disease progression, but whether smoking altered the risk of a relapse
      was largely unknown. Infections were implicated in both risk of developing MS and
      relapses, but data for progression were lacking. Specifically, exposure to the
      Epstein-Barr virus, particularly if this manifested as infectious mononucleosis
      during adolescence, was associated with increased MS risk. Upper respiratory
      tract infections were most commonly associated with an increase in relapses.
      Relapse rates typically dropped during pregnancy, but there was no strong
      evidence to suggest that pregnancy itself altered the risk of MS or affected long
      term progression. Emerging research with the greatest potential to impact public
      health was the suggestion that obesity during adolescence may increase the risk
      of MS; if confirmed, this would be of major significance.

PMID- 27045884
TI  - Trimethyltin intoxication induces the migration of ventricular/subventricular
      zone cells to the injured murine hippocampus.
AB  - Following the postnatal decline of cell proliferation in the mammalian central
      nervous system, the adult brain retains progenitor cells with stem cell-like
      properties in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the
      hippocampus. Brain injury can stimulate proliferation and redirect the migration
      pattern of SVZ precursor cells to the injury site. Sublethal exposure to the
      neurotoxicant trimethyltin (TMT) causes dose-dependent necrosis and apoptosis in
      the hippocampus dentate gyrus and increases SGZ stem cell proliferation to
      generate new granule cells. To determine whether SVZ cells also contribute to the
      repopulation of the TMT-damaged dentate gyrus, 6-8 week old male C3H mice were
      injected with the carbocyanine dye spDiI and bromodeoxyuridine (80mg/kg; ip.) to
      label ventricular cells prior to TMT exposure. The presence of labeled cells in
      hippocampus was determined 7 and 28days after TMT exposure. No significant change
      in the number of BrdU(+) and spDiI(+) cells was observed in the dentate gyrus
      7days after TMT treatment. However, 28days after TMT treatment there was a 3-4
      fold increase in the number of spDiI-labeled cells in the hippocampal hilus and
      dentate gyrus. Few spDiI(+) cells stained positive for the mature phenotypic
      markers NeuN or GFAP, suggesting they may represent undifferentiated cells. A
      small percentage of migrating cells were BrdU(+)/spDiI(+), indicating some newly
      produced, SVZ- derived precursors migrated to the hippocampus. Taken together,
      these data suggest that TMT-induced injury of the hippocampus can stimulate the
      migration of ventricular zone-derived cells to injured dentate gyrus.

PMID- 27045885
TI  - Co-expression of mouse TMEM63A, TMEM63B and TMEM63C confers hyperosmolarity
      activated ion currents in HEK293 cells.
AB  - Osmoreception is essential for systemic osmoregulation, a process to stabilize
      the tonicity and volume of the extracellular fluid through regulating the
      ingestive behaviour, sympathetic outflow and renal function. The sensation of
      osmotic changes by osmoreceptor neurons is mediated by ion channels that detect
      the change of osmolarity in extracellular fluid. However, the molecular identity
      of these channels remains mysterious. AtCSC1and OSCA1,two closely related
      paralogues from Arabidopsis, have been demonstrated to form hyperosmolarity
      activated ion channels, which makes their mammalian orthologues-the members of
      TMEM63 proteins, possible candidates for osmoreceptor transduction channel. To
      test this possibility, we cloned the cDNAs of all the three members of the mouse
      TMEM63 family, TMEM63A, TMEM63B and TMEM63C from the mRNA from mouse brain. When
      all of the three subtypes of TMEM63 proteins were co-expressed in HEK293 cells,
      we recorded membrane currents evoked by hypertonic stimulation in these cells.
      However, the cells expressing the combinations of any two subtypes of TMEM63
      proteins could not exhibit any hyperosmolarity evoked currents. Thus, all the
      three members of TMEM63 proteins are required to constitute a hyperosmolarity
      activated ion channel. We propose that the TMEM63 proteins may serve as an
      osmolarity sensitive ion channel for the osmoreception. Copyright (c) 2016 John
      Wiley & Sons, Ltd. 

PMID- 27045886
TI  - Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced
      Differentiated and Anaplastic Thyroid Cancer.
AB  - CONTEXT: Five to 10% of patients with differentiated thyroid cancers (DTC)
      develop invasive and/or distant metastatic disease that is marginally improved
      with standard therapies. Prognosis is poor for patients with anaplastic thyroid
      cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is
      necessary in the treatment of advanced cases. OBJECTIVE: We hypothesized that a T
      cell response is generated in advanced thyroid cancer and may be a viable
      therapeutic target. DESIGN: Primary DTCs were analyzed by quantitative RT-PCR (n
      = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1,
      PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow
      cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were
      analyzed by immunohistochemistry. SETTING: The study was conducted at the
      University of Colorado Hospital. PATIENTS: Thyroid cancer patients undergoing
      thyroidectomy or completion surgery for advanced disease between 2002 and 2013
      participated in the study. INTERVENTION: There were no interventions. MAIN
      OUTCOME MEASURE: Immune markers were analyzed for association with disease
      severity. RESULTS: Immune markers were commonly expressed at the RNA level. PD-L1
      was higher (P = .0443) in patients with nodal metastases. FoxP3(+) (P < .0001),
      PD-1(+)CD8(+) (P = .0058), and PD-1(+)CD4(+) (P = .0104) T cells were enriched in
      DTC biopsies. CD8(+) and FoxP3(+) T cells were detected by immunohistochemistry
      in all pT4 tumors and a subset of metastases. PD-1(+) lymphocytes were found in
      50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22
      cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373).
      BRAF(V600E) mutation was associated with higher frequencies of tumor-associated
      lymphocytes (P = .0095) but not PD-L1 expression. CONCLUSIONS: PD-1 checkpoint
      blockades may have therapeutic efficacy in patients with aggressive forms of
      thyroid cancer.

PMID- 27045887
TI  - Bottom-up Fabrication of Multilayer Stacks of 3D Photonic Crystals from Titanium
      Dioxide.
AB  - A strategy for stacking multiple ceramic 3D photonic crystals is developed.
      Periodically structured porous films are produced by vertical convective self
      assembly of polystyrene (PS) microspheres. After infiltration of the opaline
      templates by atomic layer deposition (ALD) of titania and thermal decomposition
      of the polystyrene matrix, a ceramic 3D photonic crystal is formed. Further
      layers with different sizes of pores are deposited subsequently by repetition of
      the process. The influence of process parameters on morphology and photonic
      properties of double and triple stacks is systematically studied. Prolonged
      contact of amorphous titania films with warm water during self-assembly of the
      successive templates is found to result in exaggerated roughness of the surfaces
      re-exposed to ALD. Random scattering on rough internal surfaces disrupts
      ballistic transport of incident photons into deeper layers of the multistacks.
      Substantially smoother interfaces are obtained by calcination of the structure
      after each infiltration, which converts amorphous titania into the crystalline
      anatase before resuming the ALD infiltration. High quality triple stacks
      consisting of anatase inverse opals with different pore sizes are demonstrated
      for the first time. The elaborated fabrication method shows promise for various
      applications demanding broadband dielectric reflectors or titania photonic
      crystals with a long mean free path of photons.

PMID- 27045888
TI  - [Not Available].

PMID- 27045889
TI  - [Not Available].

PMID- 27045890
TI  - [Strawberry gums].

PMID- 27045891
TI  - [The use of chewing gum stimulates bowel motility after gynaecological surgery].
AB  - Post-operative ileus is a condition which occurs after abdominal surgery. The
      incidence of post-operative ileus after gynaecological surgery is estimated to be
      10-15% (range: 5-25%). The highest rates occur after laparotomy. Chewing gum
      stimulates bowel motility after gynaecological surgery and reduces time to first
      flatulence and faeces. Data on reduction in ileus symptoms and reduced hospital
      stay are not sufficient. Chewing gum is well tolerated and this article
      recommends it for post-operative optimization. 

PMID- 27045892
TI  - [Two cases of neonatal meningitis after new gentamicin dosing guidelines].
AB  - Neonates with suspected or proven sepsis are treated with ampicillin and until
      recently with 5 mg gentamicin/kg every 24 h. New guidelines recommend the same
      gentamicin dose, but with longer intervals depending on gestational age. Two
      neonates receiving gentamicin every 48 h improved initially, but both
      deteriorated again before the second dose. In both infants ampicillin-resistant
      but gentamicin-sensitive Escherichia coli was found. In one of the infants a
      resistant/less sensitive E. coli strain was also found in the cerebrospinal
      fluid. The rationale for the new dosing guidelines is discussed. 

PMID- 27045893
TI  - [Successful treatment of supraventricular tachycardia with a modified Valsalva
      manoeuvre].
AB  - Supraventricular tachycardia (SVT) is a frequent challenge in medical emergency
      units. Adenosine, the drug of choice, may cause severe discomfort. The Danish
      Society of Cardiology's National Treatment Guidelines for SVT recommend first aid
      treatment with ''vagus stimulation such as carotid massage and Valsalva
      manoeuvre''. A disadvantage of the Valsalva manoeuvre is that only 5-20% of the
      patients convert to sinus rhythm. We describe a case story of a patient, who was
      successfully treated with ''modified Valsalva'' as described in a recently
      published study wherein 43% of the patients converted to sinus rhythm compared to
      17% in the control group. 

PMID- 27045894
TI  - Attention and attribute overlap in preferential choice.
AB  - Attributes that are common, or overlapping, across alternatives in two
      alternative forced preferential choice tasks are often non-diagnostic. In many
      settings, attending to and evaluating these attributes does not help the decision
      maker determine which of the available alternatives is the most desirable. For
      this reason, many existing behavioural theories propose that decision makers
      ignore common attributes while deliberating. Across six experiments, we find that
      decision makers do direct their attention selectively and ignore attributes that
      are not present in or associated with either of the available alternatives.
      However, they are as likely to attend to common attributes as they are to attend
      to attributes that are unique to a single alternative. These results suggest the
      need for novel theories of attention in preferential choice.

PMID- 27045895
TI  - Serial NIHSS scores in patients with acute cerebral infarction.
AB  - AIM: To study time course of neurological deficits in patients with acute
      cerebral infarction admitted shortly after stroke onset. METHODS: Serial NIHSS
      scores were obtained whenever feasible in patients admitted because of cerebral
      infarction within 3 h of symptom onset. Patients receiving and not receiving
      thrombolysis were compared. Short-term outcome was defined as NIHSS score and
      modified Rankin score 7 days after stroke onset. The hyperacute phase was defined
      as the time between stroke onset and the 6- to 9-h interval after stroke onset,
      acute phase as the time between the 6- to 9-h interval and the 21 to 27-h
      interval, and the subacute phase as the time between the 21- to 27-h interval and
      7 days after stroke onset. RESULTS: Serial NIHSS scores were obtained in 552
      patients within three hours of stroke onset. There was a significant improvement
      (P < 0.001) comprising 62% of the total improvement in the hyperacute phase.
      There was no significant improvement in the acute phase and a small significant
      improvement in the subacute phase (P < 0.01). CONCLUSION: Our study demonstrates
      a hyperacute phase with rapid improvement probably due to early recanalization,
      an acute phase with no significant improvement and slow improvement in the
      subacute phase. Different pathophysiological mechanisms are likely involved in
      the different phases.

PMID- 27045896
TI  - Carotid IMT is more associated with stroke than risk calculators.
AB  - BACKGROUND: It is unclear whether a natural marker of atherosclerosis (carotid
      intima-media thickness: CIMT) or calculated risk score is more associated with
      stroke. We therefore comparatively examined the relationship between CIMT as well
      as two cardiovascular risk calculators (Omnibus Risk Score -ORS and Framingham
      Risk Score- FRS) and the occurrence of stroke among hypertensive African
      patients. METHODS: CIMT was measured in 555 consecutive consenting hypertensive
      adults (377 stroke patients and 178 stroke-free subjects). The 10-year
      cardiovascular risk was calculated for each participant with the FRS and ORS. The
      strengths of association between FRS, ORS, CIMT, and stroke occurrence were
      examined using logistic regression. The discriminative capacity of FRS, ORS, and
      CIMT for stroke occurrence was assessed with c-statistics. RESULTS: Higher
      average CIMT (OR 11.71; 95% CI 1.65-83.07; P = 0.01) was strongly associated with
      stroke after adjusting for age, sex, blood pressure, serum cholesterol, and blood
      sugar. Neither the FRS (OR: 1.03; CI: 0.89-1.19, P = 0.68) nor the ORS (OR: 1.08;
      CI: 0.90-1.30; P = 0.41) was significantly associated with stroke. CIMT had a
      higher c-statistic for differentiating stroke patients from hypertensive controls
      (right: c = 0.63, P < 0.001; left: c = 0.67, P < 0.001; average: c = 0.66, P <
      0.001) than some conventional risk factors. Neither FRS (P = 0.39) nor ORS (P =
      0.55) was able to independently differentiate between stroke and hypertensive
      patients. CONCLUSION: CIMT, but neither FRS nor ORS, is independently associated
      with stroke among Nigerian African hypertensive patients. CIMT may be a better
      tool for estimating the overall risk of stroke than FRS or ORS in this
      population.

PMID- 27045897
TI  - Optogenetic approaches addressing extracellular modulation of neural
      excitability.
AB  - The extracellular ionic environment in neural tissue has the capacity to
      influence, and be influenced by, natural bouts of neural activity. We employed
      optogenetic approaches to control and investigate these interactions within and
      between cells, and across spatial scales. We began by developing a temporally
      precise means to study microdomain-scale interactions between extracellular
      protons and acid-sensing ion channels (ASICs). By coupling single-component
      proton-transporting optogenetic tools to ASICs to create two-component
      optogenetic constructs (TCOs), we found that acidification of the local
      extracellular membrane surface by a light-activated proton pump recruited a slow
      inward ASIC current, which required molecular proximity of the two components on
      the membrane. To elicit more global effects of activity modulation on 'bystander'
      neurons not under direct control, we used densely-expressed depolarizing (ChR2)
      or hyperpolarizing (eArch3.0, eNpHR3.0) tools to create a slow non-synaptic
      membrane current in bystander neurons, which matched the current direction seen
      in the directly modulated neurons. Extracellular protons played contributory role
      but were insufficient to explain the entire bystander effect, suggesting the
      recruitment of other mechanisms. Together, these findings present a new approach
      to the engineering of multicomponent optogenetic tools to manipulate ionic
      microdomains, and probe the complex neuronal-extracellular space interactions
      that regulate neural excitability. 

PMID- 27045898
TI  - FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for
      breast cancer growth.
AB  - The mechanisms that allow breast cancer (BCa) cells to metabolically sustain
      rapid growth are poorly understood. Here we report that BCa cells are dependent
      on a mechanism to supply precursors for intracellular lipid production derived
      from extracellular sources and that the endothelial lipase (LIPG) fulfils this
      function. LIPG expression allows the import of lipid precursors, thereby
      contributing to BCa proliferation. LIPG stands out as an essential component of
      the lipid metabolic adaptations that BCa cells, and not normal tissue, must
      undergo to support high proliferation rates. LIPG is ubiquitously and highly
      expressed under the control of FoxA1 or FoxA2 in all BCa subtypes. The
      downregulation of either LIPG or FoxA in transformed cells results in decreased
      proliferation and impaired synthesis of intracellular lipids. 

PMID- 27045899
TI  - Defects in endoplasmic reticulum-associated degradation (ERAD) increase selenate
      sensitivity in Arabidopsis.
AB  - Stress can impair protein folding in the endoplasmic reticulum (ER). Minimizing
      the accumulation of misfolded proteins in the ER is achieved by ER-associated
      degradation (ERAD), which involves the retrograde transport and proteasomal
      removal of aberrant proteins. Recently, the proteasome has been implicated in a
      selenium stress response. However, it remains unknown if selenium causes ER
      stress in plants similar to animals, and if ERAD is associated with optimal
      selenium tolerance. This deficiency was addressed by monitoring selenate-treated
      Arabidopsis plants with mutations in HRD1 and SeL1L, participants of ERAD.
      hrd1a/hrd1b and sel1l mutants treated with selenate demonstrate decreased
      tolerance and ER stress, as judged by BiP2 accumulation. The data indicate that
      optimal plant growth during selenate stress requires ERAD.

PMID- 27045900
TI  - Replication stalling and heteroduplex formation within CAG/CTG trinucleotide
      repeats by mismatch repair.
AB  - Trinucleotide repeat expansions are responsible for at least two dozen
      neurological disorders. Mechanisms leading to these large expansions of repeated
      DNA are still poorly understood. It was proposed that transient stalling of the
      replication fork by the repeat tract might trigger slippage of the newly
      synthesized strand over its template, leading to expansions or contractions of
      the triplet repeat. However, such mechanism was never formally proven. Here we
      show that replication fork pausing and CAG/CTG trinucleotide repeat instability
      are not linked, stable and unstable repeats exhibiting the same propensity to
      stall replication forks when integrated in a yeast natural chromosome. We found
      that replication fork stalling was dependent on the integrity of the mismatch
      repair system, especially the Msh2p-Msh6p complex, suggesting that direct
      interaction of MMR proteins with secondary structures formed by trinucleotide
      repeats in vivo, triggers replication fork pauses. We also show by chromatin
      immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in
      both stable and unstable orientations, this enrichment being dependent on MSH3
      and MSH6. Finally, we show that overexpressing MSH2 favors the formation of
      heteroduplex regions, leading to an increase in contractions and expansions of
      CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on
      both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant
      msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our
      results unravel two new roles for mismatch-repair proteins: stabilization of
      heteroduplex regions and transient blocking of replication forks passing through
      such repeats. Both roles may involve direct interactions between MMR proteins and
      secondary structures formed by trinucleotide repeat tracts, although indirect
      interactions may not be formally excluded.

PMID- 27045901
TI  - The relationship between cardiac hemodynamics and exercise tolerance in cystic
      fibrosis.
AB  - BACKGROUND: Individuals with cystic fibrosis (CF) have reduced pulmonary function
      and exercise tolerance. Additionally, these individuals may develop abnormal
      cardiac function. The implications of abnormal cardiac function on exercise
      tolerance are unclear in CF. OBJECTIVE: Study relationships between exercise
      cardiac hemodynamics and exercise tolerance in CF. METHODS: 17 CF and 25 controls
      participated in cardiopulmonary exercise testing to measure exercise duration and
      peak workload (PW). Cardiac index (QI) was measured using acetylene rebreathe and
      oxygen uptake (VO2) breath-by-breath. Forced expiratory volume in 1-second (FEV1)
      was performed at rest. RESULTS: Peak QI was 6.7 +/- 0.5 vs. 9.1 +/- 0.3
      mL/min/m(2), CF vs. controls, respectively (P < 0.05). Linear regressions between
      QI (R(2) = 0.63 and 0.51) and exercise duration or PW were stronger than VO2
      (R(2) = 0.35 and 0.37) or FEV1 (R(2) = 0.34 and 0.36) in CF, respectively (P <
      0.05). CONCLUSION: These data are clinically relevant suggesting attenuated
      cardiac function in addition to low airway function relate to exercise tolerance
      in CF.

PMID- 27045902
TI  - Independent lung ventilation in the management of ARDS and bronchopleural
      fistula.
AB  - Independent lung ventilation is a decades-old, but infrequently used technique
      for physiological separation in critically-ill patients with asymmetric lung
      disease. Here we present a case report of bilateral necrotizing pneumonia
      complicated by acute respiratory distress syndrome and bronchopleural fistula,
      which was successfully managed with independent lung ventilation. The use of
      independent lung ventilation allowed for adequate oxygenation with use of high
      positive end expiratory pressure in the "good lung" while simultaneously allowing
      for closure of the bronchopulmonary fistula in the contralateral lung by
      maintaining relatively low airway pressures. 

PMID- 27045903
TI  - Retrospective report of contraindications to extracorporeal membrane oxygenation
      (ECMO) among adults with acute respiratory distress syndrome (ARDS).
AB  - OBJECTIVES: To determine the incidence of contraindications to extracorporeal
      membrane oxygenation (ECMO) among adults with acute respiratory distress syndrome
      (ARDS) and assess the impact of contraindications on the number of patients
      receiving ECMO (case volume). BACKGROUND: The extent to which contraindications
      may affect case volumes has not been described. METHODS: Retrospective,
      observational study at an academic tertiary medical center. The records of 730
      consecutive patients with ARDS were queried for respiratory ECMO eligibility and
      ECMO contraindications. RESULTS: Of the 730 patients with ARDS, 168 (23.0%) met
      ECMO inclusion criteria and 515 (70.5%) never met ECMO eligibility due to
      inadequately severe disease. Among 168 patients who met ECMO inclusion criteria,
      1 or more relative contraindications were present in 144 (85.7%) patients. The
      three most common relative contraindications were immunocompromised state
      (58.3%), multiorgan dysfunction (29.2%) and contraindication to anticoagulation
      (16.7%). CONCLUSIONS: Application of relative contraindications may greatly
      affect ECMO case volumes.

PMID- 27045904
TI  - Archaeal ammonia oxidizers respond to soil factors at smaller spatial scales than
      the overall archaeal community does in a high Arctic polar oasis.
AB  - Archaea are ubiquitous and highly abundant in Arctic soils. Because of their
      oligotrophic nature, archaea play an important role in biogeochemical processes
      in nutrient-limited Arctic soils. With the existing knowledge of high archaeal
      abundance and functional potential in Arctic soils, this study employed terminal
      restriction fragment length polymorphism (t-RFLP) profiling and geostatistical
      analysis to explore spatial dependency and edaphic determinants of the overall
      archaeal (ARC) and ammonia-oxidizing archaeal (AOA) communities in a high Arctic
      polar oasis soil. ARC communities were spatially dependent at the 2-5 m scale (P
      < 0.05), whereas AOA communities were dependent at the ~1 m scale (P < 0.0001).
      Soil moisture, pH, and total carbon content were key edaphic factors driving both
      the ARC and AOA community structure. However, AOA evenness had simultaneous
      correlations with dissolved organic nitrogen and mineral nitrogen, indicating a
      possible niche differentiation for AOA in which dry mineral and wet organic soil
      microsites support different AOA genotypes. Richness, evenness, and diversity
      indices of both ARC and AOA communities showed high spatial dependency along the
      landscape and resembled scaling of edaphic factors. The spatial link between
      archaeal community structure and soil resources found in this study has
      implications for predictive understanding of archaea-driven processes in polar
      oases. 

PMID- 27045905
TI  - Isoforms of green fluorescent protein differ from each other in solvent molecules
      'trapped' inside this protein.
AB  - Green fluorescent protein (GFP) has been studied quite thoroughly, however, up to
      now some experimental data have not been explained explicitly. For example, under
      native conditions this protein can have two isoforms differing in their mobility
      in gel. In this case, no differences between the isoforms are revealed under
      denaturing conditions. In order to understand the difference in the isoforms of
      this protein, we have investigated GFP-cycle3 using mass spectrometry, gel
      electrophoresis, size exclusion chromatography, microcalorimetry, and
      spectroscopy methods under varying conditions. We have also designed and studied
      three mutant forms of this protein with substitutions of amino acid residues
      inside the GFP barrel. The mutations have allowed us to influence the formation
      of different GFP isoforms. Each of the mutant proteins has predominantly only one
      isoform. As a result of the performed research, it can be concluded that most
      likely the GFP isoforms differ in the solvent molecules 'trapped' inside the GFP
      barrel. In their turn, these molecules have an effect on the protein charge and
      consequently on its mobility at electrophoresis under native conditions.

PMID- 27045906
TI  - Prevention of gastrointestinal lead poisoning using recombinant Lactococcus
      lactis expressing human metallothionein-I fusion protein.
AB  - Low-level lead poisoning is an insidious disease that affects millions of
      children worldwide, leading to biochemical and neurological dysfunctions.
      Blocking lead uptake via the gastrointestinal tract is an important prevention
      strategy. With this in mind, we constructed the recombinant Lactococcus lactis
      strain pGSMT/MG1363, which constitutively expressed the fusion protein
      glutathione S-transferase (GST)-small molecule ubiquitin-like modifier protein
      (SUMO)-metallothionein-I (GST-SUMO-MT). The thermodynamic data indicated that the
      average number of lead bound to a GST-SUMO-MT molecule was 3.655 and this binding
      reaction was a spontaneous, exothermic and entropy-increasing process. The total
      lead-binding capacity of pGSMT/MG1363 was 4.11 +/- 0.15 mg/g dry mass. Oral
      administration of pGSMT/MG1363 (1 * 10(10) Colony-Forming Units) to pubertal male
      rats that were also treated with 5 mg/kg of lead acetate daily significantly
      inhibited the increase of blood lead levels, the impairment of hepatic function
      and the decrease of testosterone concentration in the serum, which were all
      impaired in rats treated by lead acetate alone. Moreover, the administration of
      pGSMT/MG1363 for 6 weeks did not affect the serum concentration of calcium,
      magnesium, potassium or sodium ions. This study provides a convenient and
      economical biomaterial for preventing lead poisoning via the digestive tract. 

PMID- 27045907
TI  - A Fast Iterated Orthogonal Projection Framework for Smoke Simulation.
AB  - We present a fast iterated orthogonal projection (IOP) framework for smoke
      simulations. By modifying the IOP framework with a different means for
      convergence, our framework significantly reduces the number of iterations
      required to converge to the desired precision. Our new iteration framework adds a
      divergence redistributor component to IOP that can improve the impeded
      convergence logic of IOP. We tested Jacobi, GS and SOR as divergence
      redistributors and used the Multigrid scheme to generate a highly efficient
      Poisson solver. It provides a rapid convergence rate and requires less
      computation time. In all of our experiments, our method only requires 2-3
      iterations to satisfy the convergence condition of 1e-5 and 5-7 iterations for 1e
      10. Compared with the commonly used Incomplete Cholesky Preconditioned Conjugate
      Gradient(ICPCG) solver, our Poisson solver accelerates the overall speed to
      approximately 7- to 30-fold faster for grids ranging from 128(3) to 256(3). Our
      solver can accelerate more on larger grids because of the property that the
      iteration count required to satisfy the convergence condition is independent of
      the problem size. We use various experimental scenes and settings to demonstrate
      the efficiency of our method. In addition, we present a feasible method for both
      IOP and our fast IOP to support free surfaces. 

PMID- 27045908
TI  - A Vocabulary Approach to Partial Streamline Matching and Exploratory Flow
      Visualization.
AB  - Measuring the similarity of integral curves is fundamental to many important flow
      data analysis and visualization tasks such as feature detection, pattern
      querying, streamline clustering, and hierarchical exploration. In this paper, we
      introduce FlowString, a novel vocabulary approach that extracts shape invariant
      features from streamlines and utilizes a string-based method for exploratory
      streamline analysis and visualization. Our solution first resamples streamlines
      by considering their local feature scales. We then classify resampled points
      along streamlines based on the shape similarity around their local neighborhoods.
      We encode each streamline into a string of well-selected shape characters, from
      which we construct meaningful words for querying and retrieval. A unique feature
      of our approach is that it captures intrinsic streamline similarity that is
      invariant under translation, rotation and scaling. We design an intuitive
      interface and user interactions to support flexible querying, allowing exact and
      approximate searches for partial streamline matching. Users can perform queries
      at either the character level or the word level, and define their own characters
      or words conveniently for customized search. We demonstrate the effectiveness of
      FlowString with several flow field data sets of different sizes and
      characteristics. We also extend FlowString to handle multiple data sets and
      perform an empirical expert evaluation to confirm the usefulness of this
      approach. 

PMID- 27045909
TI  - Designing Serious Games for Safety Education: "Learn to Brace" versus Traditional
      Pictorials for Aircraft Passengers.
AB  - Serious games for safety education (SGSE) are a novel tool for preparing people
      to prevent and?or handle risky situations. Although several SGSE have been
      developed, design and evaluation methods for SGSE need to be better grounded in
      and guided by safety-relevant psychological theories. In particular, this paper
      focuses on threat appeals and the assessment of variables, such as safety locus
      of control, that influence human behavior in real risky situations. It
      illustrates how we took into account such models in the design and evaluation of
      "Learn to Brace", a first-of-its-kind serious game that deals with a major
      problem in aviation safety, i.e. the scarce effectiveness of the safety cards
      used by airlines. The study considered a sample of 48 users: half of them
      received instructions about the brace position through the serious game, the
      other half through a traditional safety card pictorial. Results showed that the
      serious game was much more effective than the traditional instructions both in
      terms of learning and of changing safety-relevant perceptions, especially safety
      locus of control and recommendation perception. 

PMID- 27045910
TI  - Effects of Optical Combiner and IPD Change for Convergence on Near-Field Depth
      Perception in an Optical See-Through HMD.
AB  - Many error sources have been explored in regards to the depth perception problem
      in augmented reality environments using optical see-through head-mounted displays
      (OST-HMDs). Nonetheless, two error sources are commonly neglected: the ray-shift
      phenomenon and the change in interpupillary distance (IPD). The first source of
      error arises from the difference in refraction for virtual and see-through
      optical paths caused by an optical combiner, which is required of OST-HMDs. The
      second occurs from the change in the viewer's IPD due to eye convergence. In this
      paper, we analyze the effects of these two error sources on near-field depth
      perception and propose methods to compensate for these two types of errors.
      Furthermore, we investigate their effectiveness through an experiment comparing
      the conditions with and without our error compensation methods applied. In our
      experiment, participants estimated the egocentric depth of a virtual and a
      physical object located at seven different near-field distances (40~200 cm) using
      a perceptual matching task. Although the experimental results showed different
      patterns depending on the target distance, the results demonstrated that the near
      field depth perception error can be effectively reduced to a very small level (at
      most 1 percent error) by compensating for the two mentioned error sources.

PMID- 27045911
TI  - Multiperspective Focus+Context Visualization.
AB  - Occlusions are a severe bottleneck for the visualization of large and complex
      datasets. Conventional images only show dataset elements to which there is a
      direct line of sight, which significantly limits the information bandwidth of the
      visualization. Multiperspective visualization is a powerful approach for
      alleviating occlusions to show more than what is visible from a single viewpoint.
      However, constructing and rendering multiperspective visualizations is
      challenging. We present a framework for designing multiperspective focus+context
      visualizations with great flexibility by manipulating the underlying camera
      model. The focus region viewpoint is adapted to alleviate occlusions. The
      framework supports multiperspective visualization in three scenarios. In a first
      scenario, the viewpoint is altered independently for individual image regions to
      avoid occlusions. In a second scenario, conventional input images are connected
      into a multiperspective image. In a third scenario, one or several data subsets
      of interest (i.e., targets) are visualized where they would be seen in the
      absence of occluders, as the user navigates or the targets move. The
      multiperspective images are rendered at interactive rates, leveraging the camera
      model's fast projection operation. We demonstrate the framework on terrain,
      urban, and molecular biology geometric datasets, as well as on volume rendered
      density datasets. 

PMID- 27045912
TI  - Planning Motions and Placements for Virtual Demonstrators.
AB  - In order to deliver information effectively, virtual human demonstrators must be
      able to address complex spatial constraints and at the same time replicate motion
      coordination patterns observed in human-human interactions. We introduce in this
      paper a whole-body motion planning and synthesis framework that coordinates
      locomotion, body positioning, action execution and gaze behavior for generic
      demonstration tasks among obstacles. Human-like solutions are achieved with a
      coordination model extracted from experiments with human subjects. Given an
      observer location and a target demonstration to be performed, the proposed
      planner automatically identifies body placements respecting visibility
      constraints, locomotion accessibility, and action feasibility among obstacles.
      Actions are modeled with clusters of example motions and a fast collision
      avoidance procedure in blending space is introduced to avoid nearby obstacles
      when needed. Locomotion towards new placements integrates planning among
      obstacles and is based on a motion capture database organized for efficient
      synthesis of motions with precise path following and arrival constraints. The
      proposed solution introduces effective approaches for modeling and solving
      complex demonstrative tasks for interactive applications. 

PMID- 27045913
TI  - Styling Evolution for Tight-Fitting Garments.
AB  - We present an evolution method for designing the styling curves of garments. The
      procedure of evolution is driven by aesthetics-inspired scores to evaluate the
      quality of styling designs, where the aesthetic considerations are represented in
      the form of streamlines on human bodies. A dual representation is introduced in
      our platform to process the styling curves of designs, based on which robust
      methods for realizing the operations of evolution are developed. Starting from a
      given set of styling designs on human bodies, we demonstrate the effectiveness of
      set evolution inspired by aesthetic factors. The evolution is adaptive to the
      change of aesthetic inspirations. By this adaptation, our platform can
      automatically generate new designs fulfilling the demands of variations in
      different human bodies and poses. 

PMID- 27045914
TI  - The Effects of Avatars, Stereo Vision and Display Size on Reaching and Motion
      Reproduction.
AB  - Thanks to recent advances on motion capture devices and stereoscopic consumer
      displays, animated virtual characters can now realistically interact with users
      in a variety of applications. We investigate in this paper the effect of avatars,
      stereo vision and display size on task execution in immersive virtual
      environments. We report results obtained with three experiments in varied
      configurations that are commonly used in rehabilitation applications. The first
      experiment analyzes the accuracy of reaching tasks under different system
      configurations: with and without an avatar, with and without stereo vision, and
      employing a 2D desktop monitor versus a large multi-tile visualization display.
      The second experiment analyzes the use of avatars and user-perspective stereo
      vision on the ability to perceive and subsequently reproduce motions demonstrated
      by an autonomous virtual character. The third experiment evaluates the overall
      user experience with a complete immersive user interface for motion modeling by
      direct demonstration. Our experiments expose and quantify the benefits of using
      stereo vision and avatars, and show that the use of avatars improve the quality
      of produced motions and the resemblance of replicated msotions; however, direct
      interaction in user-perspective leads to tasks executed in less time and to
      targets more accurately reached. These and additional tradeoffs are important for
      the effective design of avatar-based training systems. 

PMID- 27045915
TI  - The Effects of Low Latency on Pointing and Steering Tasks.
AB  - Latency is detrimental to interactive systems, especially pseudo-physical systems
      that emulate real-world behaviour. It prevents users from making quick
      corrections to their movement, and causes their experience to deviate from their
      expectations. Latency is a result of the processing and transport delays inherent
      in current computer systems. As such, while a number of studies have hypothesized
      that any latency will have a degrading effect, few have been able to test this
      for latencies less than ~ 50 ms. In this study we investigate the effects of
      latency on pointing and steering tasks. We design an apparatus with a latency
      lower than typical interactive systems, using it to perform interaction tasks
      based on Fitts's law and the Steering law. We find evidence that latency begins
      to affect performance at ~ 16 ms, and that the effect is non-linear. Further, we
      find latency does not affect the various components of an aiming motion equally.
      We propose a three stage characterisation of pointing movements with each stage
      affected independently by latency. We suggest that understanding how users
      execute movement is essential for studying latency at low levels, as high level
      metrics such as total movement time may be misleading.

PMID- 27045916
TI  - Towards An Understanding of Mobile Touch Navigation in a Stereoscopic Viewing
      Environment for 3D Data Exploration.
AB  - We discuss touch-based navigation of 3D visualizations in a combined monoscopic
      and stereoscopic viewing environment. We identify a set of interaction modes, and
      a workflow that helps users transition between these modes to improve their
      interaction experience. In our discussion we analyze, in particular, the control
      display space mapping between the different reference frames of the stereoscopic
      and monoscopic displays. We show how this mapping supports interactive data
      exploration, but may also lead to conflicts between the stereoscopic and
      monoscopic views due to users' movement in space; we resolve these problems
      through synchronization. To support our discussion, we present results from an
      exploratory observational evaluation with domain experts in fluid mechanics and
      structural biology. These experts explored domain-specific datasets using
      variations of a system that embodies the interaction modes and workflows; we
      report on their interactions and qualitative feedback on the system and its
      workflow. 

PMID- 27045917
TI  - Head Tracking Latency in Virtual Environments Revisited: Do Users with Multiple
      Sclerosis Notice Latency Less?
AB  - Latency (i.e., time delay) in a virtual environment is known to disrupt user
      performance, presence and induce simulator sickness. Thus, with emerging use of
      virtual rehabilitation, the target populations' latency perception thresholds
      need to be considered to fully understand and possibly control the implications
      of latency in a Virtual Rehabilitation environment. We present a study that
      quantifies the latency discrimination thresholds of a yet untested population-a
      specific subset of mobility impaired participants where participants suffer from
      Multiple Sclerosis-and compare the results to a control group of healthy
      participants. The study was modeled after previous latency discrimination
      research and shows significant differences in latency perception between the two
      populations with MS participants showing lower sensitivity to latency than
      healthy participants. 

PMID- 27045918
TI  - Errata to "Guidelines for Effective Usage of Text Highlighting Techniques".
AB  - Presents corrections for the paper, "Guidelines for effective usage of text
      highlighting techniques," (Strobelt, H., et al), IEEE Trans. Vis. Comput.Graph.,
      vol. 22, no. 1, pp. 489-498, Jan. 2016. 

PMID- 27045919
TI  - Single and mixture toxicity of pharmaceuticals and chlorophenols to freshwater
      algae Chlorella vulgaris.
AB  - Organisms in the aquatic environment are exposed to a variety of substances of
      numerous chemical classes. The unintentional co-occurrence of pharmaceuticals and
      other contaminants of emerging concern may pose risk to non-target organisms. In
      this study, individual and binary mixture toxicity experiments of selected
      pharmaceuticals (ibuprofen and ciprofloxacin) and chlorophenols (2.4
      dichlorophenol (2,4-DCP) and 3-chlorophenol (3-CP)) have been performed with
      freshwater algae Chlorella vulgaris. All experiments have been carried out
      according to the 96-h algal growth inhibition test OECD No. 201. Binary mixture
      tests were conducted using proportions of the respective IC50s in terms of toxic
      unit (TU). The mixture concentration-response curve was compared to predicted
      effects based on both the concentration addition (CA) and the independent action
      (IA) model. Additionally, the Combination Index (CI)-isobologram equation method
      was used to assess toxicological interactions of the binary mixtures. All
      substances individually tested had a significant effect on C. vulgaris population
      density and revealed IC50 values <100mgL(-1) after exposure period of 96-h. The
      toxic ranking of these four compounds to C. vulgaris was 2,4-DCP>ciprofloxacin>3
      CP>ibuprofen. Generally, it can be concluded from this study that toxic mixture
      effects of all tested chemicals to C. vulgaris are higher than the individual
      effect of each mixture component. It could be demonstrated that IC50 values of
      the tested mixtures predominately lead to additive effects. The CA model is
      appropriate to estimate mixture toxicity, while the IA model tends to
      underestimate the joint effect. The CI-isobologram equation method predicted the
      mixtures accurately and elicited synergism at low effect levels for the majority
      of tested combinations.

PMID- 27045920
TI  - An exploration of spatial human health risk assessment of soil toxic metals under
      different land uses using sequential indicator simulation.
AB  - A modified method was proposed which integrates the spatial patterns of toxic
      metals simulated by sequential indicator simulation, different exposure models
      and local current land uses extracted by remote-sensing software into a dose
      response model for human health risk assessment of toxic metals. A total of 156
      soil samples with a various land uses containing farm land (F1-F25), forest land
      (W1-W12) and residential land (U1-U15) were collected in a grid pattern
      throughout Xiandao District (XDD), Hunan Province, China. The total Cr and Pb in
      topsoil were analyzed. Compared with Hunan soil background values, the elevated
      concentrations of Cr were mainly located in the east of XDD, and the elevated
      concentrations of Pb were scattered in the areas around F1, F6, F8, F13, F14, U5,
      U14, W2 and W11. For non-carcinogenic effects, the hazard index (HI) of Cr and Pb
      overall the XDD did not exceed the accepted level to adults. While to children,
      Cr and Pb exhibited HI higher than the accepted level around some areas. The
      assessment results indicated Cr and Pb should be regarded as the priority
      pollutants of concern in XDD. The first priority areas of concern were identified
      in region A with a high probability (>0.95) of risk in excess of the accepted
      level for Cr and Pb. The areas with probability of risk between 0.85 and 0.95 in
      region A were identified to be the secondary priority areas for Cr and Pb. The
      modified method was proved useful due to its improvement on previous studies and
      calculating a more realistic human health risk, thus reducing the probability of
      excessive environmental management.

PMID- 27045921
TI  - Nonionic surfactants induced changes in cell characteristics and phenanthrene
      degradation ability of Sphingomonas sp. GY2B.
AB  - Surfactant-mediated bioremediation has been widely applied in decontaminating PAH
      polluted sites. However, the impacts of surfactants on the biodegradation of PAHs
      have been controversial in the past years. To gain a clear insight into the
      influencing mechanisms, three nonionic surfactants (Tween80, TritonX-100 and
      Brij30) were selected to systematically investigate their effects on cell surface
      properties (membrane permeability, functional groups and elements), cell vitality
      as well as subsequent phenanthrene degradation ability of Sphingomonas sp. GY2B.
      Results showed that biodegradation of phenanthrene was stimulated by Tween80,
      slightly inhibited by TritonX-100 and severely inhibited by Brij30, respectively.
      Positive effect of Tween80 may arise from its role as the additional carbon
      source for GY2B to increase bacterial growth and activity, as demonstrated by the
      increasing viable cells in Tween80 amended degradation systems determined by flow
      cytometry. Although TritonX-100 could inhibit bacterial growth and disrupt cell
      membrane, its adverse impacts on microbial cells were weaker than Brij30, which
      may result in its weaker inhibitive extent. Results from this study can provide a
      rational basis on selecting surfactants for enhancing bioremediation of PAHs.

PMID- 27045922
TI  - Clinical Features and Outcomes of Complementary and Alternative Medicine Induced
      Acute Liver Failure and Injury.
AB  - OBJECTIVES: The increasing use of complementary and alternative medicines (CAMs)
      has been associated with a rising incidence of CAM-induced drug-induced liver
      injury (DILI). The aim of this study was to examine the clinical features and
      outcomes among patients with acute liver failure (ALF) and acute liver injury
      (ALI) enrolled in the Acute Liver Failure Study Group database, comparing CAM
      induced with prescription medicine (PM)-induced DILI. METHODS: A total of 2,626
      hospitalized patients with ALF/ALI of any etiology were prospectively enrolled
      between 1998 and 2015 from 32 academic transplant centers. Only those with CAM or
      PM-induced ALI/ALF were selected for analysis. RESULTS: A total of 253 (9.6%)
      subjects were found to have idiosyncratic DILI, of which 41 (16.3%) were from CAM
      and 210 (83.7%) were due to PM. The fraction of DILI-ALF/ALI cases due to CAM
      increased from 1998-2007 to 2007-2015 (12.4 vs. 21.1%, P=0.047). There was no
      difference in the type of liver injury-hepatocellular, cholestatic, or mixed
      between groups as determined by R score (P=0.26). PM-induced DILI showed higher
      serum alkaline phosphatase levels compared with the CAM group (median IU/L, 171
      vs. 125, P=0.003). The CAM population had fewer comorbid conditions (1.0 vs. 2.0,
      P<0.005), higher transplantation rates (56 vs. 32%, P<0.005), and a lower ALF
      specific 21-day transplant-free survival (17 vs. 34%, P=0.044). CONCLUSIONS: CAM
      induced DILI is at least as severe in presentation as that observed due to PM
      with higher rates of transplantation and lower transplant-free survival in those
      who progress to ALF. This study highlights the increasing incidence of CAM
      induced liver injury and emphasizes the importance of early referral and
      evaluation for liver transplantation when CAM-induced liver injury is suspected.

PMID- 27045923
TI  - Assessing the Durability of Entecavir-Treated Hepatitis B Using Quantitative
      HBsAg.
AB  - OBJECTIVES: This study aims to assess whether quantitative HBsAg can predict
      durability of chronic hepatitis B (CHB) patients stopping entecavir (ETV)
      treatment. METHODS: We conducted a multicenter study on non-cirrhotic CHB
      patients who discontinued ETV treatment. The primary end points were clinical
      relapse and sustained viral response (SVR), which was defined as undetectable
      serum hepatitis B virus (HBV) DNA levels (<6 IU/ml) at 12 months off-therapy.
      RESULTS: A total of 117 consecutive CHB patients were enrolled. Among them, 93
      patients who received more than 1-year off-therapy follow-up were included for
      the final analysis. The duration of off-therapy follow-up was 24.8+/-11.6 months.
      All 12 patients who did not achieve therapeutic end points had clinical relapse.
      In 81 patients who achieved therapeutic end points, clinical relapse and SVR were
      observed in 44 (54.3%) and 11 (13.6%) patients, respectively. The serum HBV DNA
      at 3 months and 6 months off-therapy were associated with clinical relapse over
      time, whereas quantitative hepatitis B surface antigen (qHBsAg) level at 6 months
      off-therapy had a marginal effect. Furthermore, end-of-treatment qHBsAg levels
      were associated with SVR (P=0.009). CONCLUSIONS: The serum qHBsAg level off
      therapy can predict durability of ETV-treated CHB patients. It may guide
      clinicians to select which patients can maintain sustained viral suppression or
      need retreatment after discontinuing ETV treatment.

PMID- 27045924
TI  - Decreasing Mortality Among Danish Alcoholic Cirrhosis Patients: A Nationwide
      Cohort Study.
AB  - OBJECTIVES: Clinical management of certain cirrhosis complications has improved
      over the last two decades. In this study we aimed to examine whether mortality
      among Danish alcoholic cirrhosis patients has decreased during this period.
      METHODS: In this historical cohort study we used nationwide hospital data to
      identify Danish alcoholic cirrhosis patients diagnosed in 1996-1998, 1999-2001,
      2002-2004, 2005-2007, 2008-2010, and 2011-2013. We used Cox regression to examine
      time trends in mortality after cirrhosis diagnosis, adjusting for confounding by
      age, gender, and prevalence of variceal bleeding, ascites, hepatorenal syndrome,
      alcoholic hepatitis, infection, hepatocellular carcinoma, comorbidity, and in
      patient status at the time of cirrhosis diagnosis. RESULTS: We included 22,734
      patients (69% men). The adjusted mortality hazard ratio (HR) for patients
      diagnosed in each period compared with those diagnosed in 1996-1998 was 0.99 (95%
      confidence interval (CI): 0.92-1.06) in 1999-2001, 1.00 (95% CI: 0.94-1.08) in
      2002-2004, 0.97 (95% CI: 0.90-1.04) in 2005-2007, 0.94 (95% CI: 0.88-1.01) in
      2008-2010, and finally 0.84 (95% CI: 0.79-0.90) in 2011-2013. CONCLUSIONS: In
      recent years, mortality among Danish alcoholic cirrhosis patients has decreased.

PMID- 27045925
TI  - The Advantages and Challenges of Measuring Patient Experience in Outpatient
      Clinical Practice. Part 3: Patient Satisfaction and Your Practice.

PMID- 27045926
TI  - Metagenomics Reveals Dysbiosis and a Potentially Pathogenic N. flavescens Strain
      in Duodenum of Adult Celiac Patients.
AB  - OBJECTIVES: Celiac disease (CD)-associated duodenal dysbiosis has not yet been
      clearly defined, and the mechanisms by which CD-associated dysbiosis could concur
      to CD development or exacerbation are unknown. In this study, we analyzed the
      duodenal microbiome of CD patients. METHODS: The microbiome was evaluated in
      duodenal biopsy samples of 20 adult patients with active CD, 6 CD patients on a
      gluten-free diet, and 15 controls by DNA sequencing of 16S ribosomal RNA
      libraries. Bacterial species were cultured, isolated and identified by mass
      spectrometry. Isolated bacterial species were used to infect CaCo-2 cells, and to
      stimulate normal duodenal explants and cultured human and murine dendritic cells
      (DCs). Inflammatory markers and cytokines were evaluated by immunofluorescence
      and ELISA, respectively. RESULTS: Proteobacteria was the most abundant and
      Firmicutes and Actinobacteria the least abundant phyla in the microbiome profiles
      of active CD patients. Members of the Neisseria genus (Betaproteobacteria class)
      were significantly more abundant in active CD patients than in the other two
      groups (P=0.03). Neisseria flavescens (CD-Nf) was the most abundant Neisseria
      species in active CD duodenum. Whole-genome sequencing of CD-Nf and control-Nf
      showed genetic diversity of the iron acquisition systems and of some hemoglobin
      related genes. CD-Nf was able to escape the lysosomal compartment in CaCo-2 cells
      and to induce an inflammatory response in DCs and in ex-vivo mucosal explants.
      CONCLUSIONS: Marked dysbiosis and an abundance of a peculiar CD-Nf strain
      characterize the duodenal microbiome in active CD patients thus suggesting that
      the CD-associated microbiota could contribute to the many inflammatory signals in
      this disorder.

PMID- 27045927
TI  - Association Between Affective-Cognitive Symptoms of Depression and Exacerbation
      of Crohn's Disease.
AB  - OBJECTIVES: The prevalence of depression is high in patients with Crohn's disease
      (CD). We examined the influence of affective-cognitive symptoms of depression on
      the risk of exacerbation of CD. METHODS: We studied 2,144 adult volunteers with a
      self-reported diagnosis of CD who completed a baseline survey that included
      demographics, CD status, and an affective-cognitive index of depression. Linear
      and logistic regression analyses were used to determine whether CD status at 12
      months was associated with the baseline measure of depression. Analyses were
      adjusted for confounders including age, gender, race, baseline disease activity,
      disease duration, prior hospitalization and surgery, corticosteroid and anti-TNF
      use, medication adherence, body mass index, current smoking, education, and sleep
      quality. RESULTS: Depression was significantly associated with subsequent
      increases in SCDAI score in both unadjusted (P<0.001) and adjusted (P<0.001)
      analyses. This association was non-linear, with a shallower slope for lower
      levels of depression. A 10-point increase in depression t-scores from 55 to 65
      was associated with a 18.6-point increase in SCDAI (95% CI 11.5-25.6) and an odds
      ratio of 1.27 for SCDAI>150 at follow-up (CI: 1.01-1.60). We also found a
      significant association between depressive symptoms and hospitalization.
      CONCLUSIONS: Cognitive-affective depressive symptoms were significantly
      associated with a risk of exacerbation of CD and hospitalization.

PMID- 27045928
TI  - The Advantages and Challenges of Measuring Patient Experience in Outpatient
      Clinical Practice. Part 1: Current Medicare Physician Quality Reporting Programs.

PMID- 27045929
TI  - Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or
      Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing
      Agents.
AB  - OBJECTIVES: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that
      increase gastric pH can alter the bioavailability of antiviral drugs,
      particularly relevant in patients with advanced liver disease caused by chronic
      hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six
      phase 3 studies, we report the safety and efficacy of the 3-direct-acting
      antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir
      boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV,
      an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1
      patients taking concomitant ARAs and PPIs. METHODS: Treatment-naive or
      peginterferon/RBV treatment-experienced patients with or without compensated
      cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of
      sustained virologic response (SVR), defined as HCV RNA below the lower limit of
      quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in
      patients who were receiving concomitant ARAs. RESULTS: Among 2,053 patients
      enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of
      these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95%
      confidence interval (CI) 93.5-97.4%) among patients receiving an ARA, and 96.3%
      (95% CI 95.3-97.2%) in patients not receiving a concomitant ARA. Similarly, among
      patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1-97.0%)
      and 96.4% (95% CI 95.5-97.2%), respectively. Response rates were high regardless
      of treatment regimen (with or without RBV), and among patients receiving a
      standard or high dose of PPIs. Regarding safety, adverse events and serious
      adverse events were more frequently reported in patients taking concomitant ARAs,
      though baseline population differences may have played a role. CONCLUSIONS: In
      phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients,
      SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support
      the co-administration of this regimen with ARAs including PPIs.

PMID- 27045930
TI  - 2015 American Journal of Gastroenterology Lecture: How Digital Health Will
      Transform Gastroenterology.
AB  - Our patients spend most of their lives far away from an examination room. If we
      are truly going to capture our patients' attention and engage them in their care,
      then we must reach beyond the four walls of the clinic, hospital, or endoscopy
      suite. This is the vision of the digital health movement-an effort to monitor
      patients remotely and dynamically with mobile health ("mHealth") smartphone
      applications, electronic health record portals, social media, and wearable
      biosensors to improve health care outside of the clinical trenches. This article
      explores how advances in digital health may improve health-care delivery,
      focusing on gastroenterology and hepatology. It describes how technology can
      monitor patients remotely, improve face-to-face care, drive clinical decisions,
      and offer value to health-care organizations, their patients, and their staff.
      The article also describes pitfalls and shortcomings of digital technologies and
      concludes by describing a new model for how digital health can be deployed at
      scale to improve coordination and outcomes of care.

PMID- 27045931
TI  - The Advantages and Challenges of Measuring Patient Experience in Outpatient
      Clinical Practice. Part 2: History of Patient Satisfaction in Health Care.

PMID- 27045932
TI  - Salt Effects on Surface Structures of Polyelectrolyte Multilayers (PEMs)
      Investigated by Vibrational Sum Frequency Generation (SFG) Spectroscopy.
AB  - Sum frequency generation (SFG) vibrational spectroscopy was employed to
      investigate the surface structures of polyelectrolyte multilayers (PEMs)
      constructed by sequentially alternating adsorption of
      poly(diallyldimethylammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS).
      It was found that the surface structures and surface charge density of the as
      deposited PEMs of PDDA/PSS significantly depend on the concentration of sodium
      chloride (NaCl) present in the polyelectrolyte solutions. Furthermore, it was
      found that the surface structure of the as-deposited PEMs is in a metastable
      state and will reach the equilibrium state by diffusion of the polyelectrolyte
      chain after an aging process, resulting in a polyelectrolyte mixture on the PEM
      surfaces.

PMID- 27045933
TI  - Particle-Scale Modeling of Methane Emission during Pig Manure/Wheat Straw Aerobic
      Composting.
AB  - Inefficient aerobic composting techniques significantly contribute to the
      atmospheric methane (CH4) levels. Macro-scale models assuming completely aerobic
      conditions cannot be used to analyze CH4 generation in strictly anaerobic
      environments. This study presents a particle-scale model for aerobic pig
      manure/wheat straw composting that incorporates CH4 generation and oxidation
      kinetics. Parameter estimation revealed that pig manure is characterized by high
      CH4 yield coefficient (0.6414 mol CH4 mol(-1) Cman) and maximum CH4 oxidation
      rate (0.0205 mol CH4 kg(-1) VS(aero) h(-1)). The model accurately predicted CH4
      emissions (R(2) = 0.94, RMSE = 2888 ppmv, peak time deviation = 0 h),
      particularly in the self-heating and cooling phases. During mesophilic and
      thermophilic stages, a rapid increase of CH4 generation (0.0130 mol CH4 kg(-1) VS
      h(-1)) and methanotroph inactivation were simulated, implying that additional
      measures should be performed during these phases to mitigate CH4 emissions.
      Furthermore, CH4 oxidation efficiency was related to oxygen permeation through
      the composting particles. Reducing the ambient temperature and extending the
      aeration duration can decrease CH4 emission, but the threshold temperature is
      required to trigger the self-heating phase. These findings provide insights into
      CH4 emission during composting and may inform responsible strategies to
      counteract climate change.

PMID- 27045934
TI  - No association between global DNA methylation in peripheral blood and lung cancer
      risk in nonsmoking women: results from a multicenter study in Eastern and Central
      Europe.
AB  - Alterations in global DNA methylation have been suggested to play an important
      role in cancer development. We evaluated the association of global DNA
      methylation in peripheral blood with the risk of lung cancer in nonsmoking women
      from six countries in Central and Eastern Europe. This multicenter case-control
      study included primary, incident lung cancer cases diagnosed from 1998 to 2001
      and controls frequency-matched for geographic area, sex, and age. Global
      methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases
      and 181 nonsmoking female controls using the luminometric methylation assay
      (LUMA). Unconditional logistic regression models were used to estimate
      associations between DNA methylation in the blood and the risk of lung cancer.
      LUMA methylation level was not associated with the risk of lung cancer in
      nonsmoking women. Associations were not significantly different according to
      different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke
      exposure status. In our study of nonsmoking women, the LUMA methylation level in
      peripheral blood was not associated with the risk of lung cancer. Our findings do
      not support an association of global blood DNA methylation with the risk of lung
      cancer in nonsmoking women.

PMID- 27045935
TI  - Does Enhanced External Counterpulsation (EECP) Significantly Affect Myocardial
      Perfusion?: A Systematic Review & Meta-Analysis.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) is currently applied for
      treating coronary artery disease (CAD) patients. However, the mechanism(s) by
      which EECP ameliorates angina pectoris and long-term left ventricular function
      remain largely unknown. The aim of this study will be to assess whether EECP
      significantly affects myocardial perfusion in CAD patients through a systematic
      review and meta-analysis of the available literature. METHODS: MEDLINE, EMBASE,
      and Cochrane CENTRAL databases were searched for prospective studies on CAD
      patients that underwent EECP and reported myocardial perfusion data pre- and post
      EECP. The impact of EECP was assessed based on the weighted mean difference (WMD)
      in myocardial perfusion from pre-EECP to post-EECP. Statistical heterogeneity was
      assessed by the I2 index. Publication bias was assessed through visual inspection
      of the funnel plot as well as Begg's and Egger's testing. RESULTS: Standard EECP
      therapy (i.e., 35-36 one-hour sessions within a seven-week period) significantly
      increased myocardial perfusion in CAD patients (pooled WMD: -0.19, 95% CI: -0.38
      to 0.00, p = 0.049). A random effects analysis was applied on account of
      significant heterogeneity (I2 = 89.1%, p = 0.000). There was no evidence of
      significant publication bias (Begg's p = 0.091; Egger's p = 0.282). CONCLUSIONS:
      Standard EECP therapy significantly increases myocardial perfusion in CAD
      patients. This study's findings support the continued use of standard EECP
      therapy in CAD patients and provides one putative physiological mechanism to help
      explain the improvements in angina pectoris and long-term left ventricular
      function observed in CAD patients after EECP therapy.

PMID- 27045936
TI  - Microchannel Voltammetry in the Presence of Large External Voltages and Electric
      Fields.
AB  - The ability to perform electrochemistry in the presence of large voltages and
      electric field magnitudes without concern for the local potential has many
      possible applications in micro/nanofluidic assays and in capillary
      electrophoresis. Traditionally, electrochemistry in the presence of significant
      external electric fields has been dominated by end-channel detection for
      capillary and microchip electrophoresis detection. We describe novel
      instrumentation for potentiostatically controlled voltammetry that can be applied
      in the presence of high external voltages and electric fields. Cyclic voltammetry
      is demonstrated without significant shifts in the half-wave potential at working
      electrodes at local potentials of up to ~1500 V and field strengths of up to 3000
      V/cm, using a standard Ag/AgCl reference electrode. 

PMID- 27045937
TI  - Dialysis membrane: from convection to adsorption.
AB  - Although patients undergoing dialysis have a complex illness, there are
      compelling reasons to believe that the inadequate removal of organic waste is an
      important contributing factor to the illness itself. This paper focuses on the
      transport phenomena that occur within a dialyser. An attempt is made to clarify
      how transport phenomena are related to the performance of a dialysis session and
      how they depend on the membrane characteristics. Our study offers some discussion
      points on the complex issue of defining what the best parameters could be in
      comparing the efficiency of different membranes. The new high-flux dialysers have
      improved larger-molecule clearance and biocompatibility. Membrane performance is
      a very hard process to evaluate, and different membranes can only be compared by
      establishing adequate points of comparison. At the same time, the points of
      comparison themselves may change depending on the type of co-morbidities of the
      specific patient who is considered for membrane selection. This editorial
      (together with all the papers presented in this issue) seeks to focus on the
      membrane's own merits in improving the dialysis therapy.

PMID- 27045938
TI  - Challenges in Implementing Evidence-Based Practices and Programs in Nonprofit
      Human Service Organizations.
AB  - Evidence-based practice (EBP) is an important, yet under-utilized strategy to
      improve social work practice. Nonprofit human service organizations (NPHSOs) are
      a common social work practice setting through which efforts to promote EBP ought
      to be better understood. NPHSOs experience capacity limitations, lack of access
      to research evidence, and funding difficulties which makes adopting,
      implementing, and sustaining EBP challenging, if not untenable. These challenges
      are more acute for NPHSOs in practice fields for which little top tier
      intervention research evidence, dissemination platforms, and funding programs
      exist. Recommendations for overcoming these challenges are discussed.

PMID- 27045939
TI  - On-chip droplet production regimes using surface acoustic waves.
AB  - Aqueous droplets suspended in an immiscible carrier fluid are a key tool in
      microfluidic chemical analysis platforms. The approaches for producing droplets
      in microfluidic devices can be divided into three general categories: batch
      emulsification, continuous production and tailored on-demand production. The
      major distinctions between each category are the rate of production and the
      degree of control over the droplet formation process in terms of the size and
      quantity. On-demand methods are highly desirable when, for example, small numbers
      or even single droplets of one sample type are required at a time. Here, we
      present a method for the on-demand production of femtolitre droplets, utilising a
      pressure source generated by high frequency surface acoustic waves (SAW). An
      increase in the continuous phase flow rate is enabled by a quasi-3D feature at
      the droplet production nozzle. A wide range of accessible flow rates permits the
      identification of different physical regimes in which droplets of different
      dimensions are produced. In the system investigated droplets measuring as little
      as 200 fl have been produced, ~1/60th of the minimum volume previously reported.
      The experimental findings are supported by a numerical model which demonstrates
      the link between the number of droplets formed and the pulse length used.

PMID- 27045940
TI  - Proteomic analysis reveals growth inhibition of soybean roots by manganese
      toxicity is associated with alteration of cell wall structure and lignification.
AB  - Plant roots, the hidden half of plants, play a vital role in manganese (Mn)
      toxicity tolerance. However, molecular mechanisms underlying root adaptation to
      Mn toxicity remain largely unknown. In this study, soybean (Glycine max) was used
      to investigate alterations of root morphology and protein profiles in response to
      Mn toxicity. Results showed that soybean root growth was significantly inhibited
      by Mn toxicity. Subsequent proteomic analysis revealed that 31 proteins were
      successfully identified via MALDI TOF/TOF MS analysis including 21 unique up
      regulated and 6 unique down-regulated proteins, which are mainly related to cell
      wall metabolism, protein metabolism and signal transduction. qRT-PCR analysis
      revealed that corresponding gene transcription patterns were correlated with
      accumulation of 14 of 21 up-regulated proteins, but only 1 of 6 down-regulated
      proteins, suggesting that most excess Mn up-regulated proteins are controlled at
      the transcriptional levels, while down-regulated proteins are controlled at the
      post-transcriptional levels. Furthermore, changes in abundances of GTP-binding
      nuclear protein Ran-3, expansin-like B1-like protein, dirigent protein and
      peroxidase 5-like protein strongly suggested that alteration of root cell wall
      structure and lignification might be associated with inhibited root growth. Taken
      together, this study was helpful to further understandings of adaptive strategies
      of legume roots to Mn toxicity. SIGNIFICANCE: This study highlighted the effects
      of Mn toxicity on soybean root growth and its proteome profiles. Excess Mn
      treatments inhibited root growth. Comparative proteomic analysis was performed to
      analyze the changes in protein profiles of soybean roots in response to Mn
      toxicity. A total of 31 root proteins with differential abundances were
      identified and predominantly associated with signal transduction and cell wall
      metabolism. Among them, the abundances of the GTP-binding nuclear protein Ran-3
      and Ran-binding protein 1 were significantly increased, suggesting that the
      proteins could be involved in the signaling network in soybean roots responsive
      to Mn toxicity. Interestingly, three 14-3-3 proteins were decreased by excess Mn
      at protein but not mRNA levels, suggesting that these proteins could be regulated
      at post-transcriptional modification under Mn excess conditions. Furthermore,
      changes in abundances of expansin-like B1-like protein, peroxidase 5-like
      protein, dirigent protein 2-like protein and dirigent protein strongly suggested
      that Mn toxicity could influence root cell wall modification, and thus inhibit
      root growth. This study provided significant insights into the potential
      molecular mechanisms underlying soybean root adaptation to Mn toxicity, which was
      mainly through alteration of root cell wall structure and lignification.

PMID- 27045941
TI  - Effects of Fe deficiency on the protein profiles and lignin composition of stem
      tissues from Medicago truncatula in absence or presence of calcium carbonate.
AB  - Iron deficiency is a yield-limiting factor with major implications for crop
      production, especially in soils with high CaCO3. Because stems are essential for
      the delivery of nutrients to the shoots, the aim of this work was to study the
      effects of Fe deficiency on the stem proteome of Medicago truncatula. Two
      dimensional electrophoresis separation of stem protein extracts resolved 276
      consistent spots in the whole experiment. Iron deficiency in absence or presence
      of CaCO3 caused significant changes in relative abundance in 10 and 31 spots,
      respectively, and 80% of them were identified by mass spectrometry. Overall
      results indicate that Fe deficiency by itself has a mild effect on the stem
      proteome, whereas Fe deficiency in the presence of CaCO3 has a stronger impact
      and causes changes in a larger number of proteins, including increases in stress
      and protein metabolism related proteins not observed in the absence of CaCO3.
      Both treatments resulted in increases in cell wall related proteins, which were
      more intense in the presence of CaCO3. The increases induced by Fe-deficiency in
      the lignin per protein ratio and changes in the lignin monomer composition,
      assessed by pyrolysis-gas chromatography-mass spectrometry and microscopy,
      respectively, further support the existence of cell wall alterations. BIOLOGICAL
      SIGNIFICANCE: In spite of being essential for the delivery of nutrients to the
      shoots, our knowledge of stem responses to nutrient deficiencies is very limited.
      The present work applies 2-DE techniques to unravel the response of this
      understudied tissue to Fe deficiency. Proteomics data, complemented with mineral,
      lignin and microscopy analyses, indicate that stems respond to Fe deficiency by
      increasing stress and defense related proteins, probably in response of mineral
      and osmotic unbalances, and eliciting significant changes in cell wall
      composition. The changes observed are likely to ultimately affect solute
      transport and distribution to the leaves.

PMID- 27045942
TI  - Unravelling the effect of clostridia spores and lysozyme on microbiota dynamics
      in Grana Padano cheese: A metaproteomics approach.
AB  - Grana Padano is a typical Italian Protected Designation of Origin (PDO) hard
      cheese largely consumed all over the world. The major problem during its
      production is represented by late blowing. Clostridia are gasogen bacteria
      responsible of the swelling during ripening, and they are partially counteracted
      by the use of egg white lysozyme as additive. In this work was applied, for the
      first time in cheese, a metaproteomic approach that identified the functional
      dynamics of microbial consortia in relation to the number of clostridial spores
      and lysozyme treatment using experimental samples of Grana Padano cheese. We used
      a combined custom BLAST+/MEGAN/STAMP approach to obtain a global taxonomic view
      associated to low and high clostridial spores cheese without and with lysozyme.
      Main differences were highlighted in the bacilli class. Functional analysis with
      SEED provided a deep view into several metabolic pathways, highlighting the
      subsystems "amino acid and derivatives" and "clustering-based subsystem" as the
      targeted subsystems during lysozyme treatment in the high spore group. In these
      subsystems, acetate kinase from clostridia was one of the main enzymes affected
      by the lysozyme treatment. BIOLOGICAL SIGNIFICANCE: Metaproteomics is a very
      promising and useful technique in the control of food safety and quality, from
      fresh products until 'ready to eat' food. Tools able to identify at molecular
      level the dynamic fingerprinting of food microbiota could be of great help to
      improve food safety and quality.

PMID- 27045943
TI  - MspA nanopore as a single-molecule tool: From sequencing to SPRNT.
AB  - Single-molecule picometer resolution nanopore tweezers (SPRNT) is a new tool for
      analyzing the motion of nucleic acids through molecular motors. With SPRNT,
      individual enzymatic motions along DNA as small as 40pm can be resolved on sub
      millisecond time scales. Additionally, SPRNT reveals an enzyme's exact location
      with respect to a DNA strand's nucleotide sequence, enabling identification of
      sequence-specific behaviors. SPRNT is enabled by a mutant version of the
      biological nanopore formed by Mycobacterium smegmatis porin A (MspA). SPRNT is
      strongly rooted in nanopore sequencing and therefore requires a solid
      understanding of basic principles of nanopore sequencing. Furthermore, SPRNT
      shares tools developed for nanopore sequencing and extends them to analysis of
      single-molecule kinetics. As such, this review begins with a brief history of our
      work developing the nanopore MspA for nanopore sequencing. We then describe the
      underlying principles of SPRNT, how it works in detail, and propose some
      potential future uses. We close with a comparison of SPRNT to other techniques
      and we present the methods that will enable others to use SPRNT.

PMID- 27045944
TI  - Nanometer resolved single-molecule colocalization of nuclear factors by two-color
      super resolution microscopy imaging.
AB  - In order to study the detailed assembly and regulation mechanisms of complex
      structures and machineries in the cell, simultaneous in situ observation of all
      the individual interacting components should be achieved. Multi-color Single
      Molecule Localization Microscopy (SMLM) is ideally suited for these
      quantifications. Here, we build on previous developments and thoroughly discuss a
      protocol for two-color SMLM combining PALM and STORM, including sample
      preparation details, image acquisition and data postprocessing analysis. We
      implement and evaluate a recently proposed colocalization analysis method (aCBC)
      that allows single-molecule colocalization quantification with the potential of
      revealing fine, nanometer-scaled, structural details of multicomponent complexes.
      Finally, using a doubly-labeled nuclear factor (Beaf-32) in Drosophila S2 cells
      we experimentally validate the colocalization quantification algorithm, highlight
      its advantages and discuss how using high molecular weight fluorescently labeled
      tags compromises colocalization precision in two-color SMLM experiments.

PMID- 27045947
TI  - A basin-hopping Monte Carlo investigation of the structural and energetic
      properties of 55- and 561-atom bimetallic nanoclusters: the examples of the ZrCu,
      ZrAl, and CuAl systems.
AB  - We report a basin-hopping Monte Carlo investigation within the embedded-atom
      method of the structural and energetic properties of bimetallic ZrCu, ZrAl, and
      CuAl nanoclusters with 55 and 561 atoms. We found that unary Zr55, Zr561, Cu55,
      Cu561, Al55, and Al561 systems adopt the well known compact icosahedron (ICO)
      structure. The excess energy is negative for all systems and compositions, which
      indicates an energetic preference for the mixing of both chemical species. The
      ICO structure is preserved if a few atoms of the host system are replaced by
      different species, however, the composition limit in which the ICO structure is
      preserved depends on both the host and new chemical species. Using several
      structural analyses, three classes of structures, namely ideal ICO, nearly ICO,
      and distorted ICO structures, were identified. As the amounts of both chemical
      species change towards a more balanced composition, configurations far from the
      ICO structure arise and the dominant structures are nearly spherical, which
      indicates a strong minimization of the surface energy by decreasing the number of
      atoms with lower coordination on the surface. The average bond lengths follow
      Vegard's law almost exactly for ZrCu and ZrAl, however, this is not the case for
      CuAl. Furthermore, the radial distribution allowed us to identify the presence of
      an onion-like behavior in the surface of the 561-atom CuAl nanocluster with the
      Al atoms located in the outermost surface shell, which can be explained by the
      lower surface energies of the Al surfaces compared with the Cu surfaces. In ZrCu
      and ZrAl the radial distribution indicates a nearly homogeneous distribution for
      the chemical species, however, with a slightly higher concentration of Al atoms
      on the ZrAl surface, which can also be explained by the lower surface energy. 

PMID- 27045948
TI  - A Study of H2O2 with Threshold Photoelectron Spectroscopy (TPES) and Electronic
      Structure Calculations: Redetermination of the First Adiabatic Ionization Energy
      (AIE).
AB  - In this work, hydrogen peroxide has been studied with threshold photoelectron
      (TPE) spectroscopy and photoelectron (PE) spectroscopy. The TPE spectrum has been
      recorded in the 10.0-21.0 eV ionization energy region, and the PE spectrum has
      been recorded at 21.22 eV photon energy. Five bands have been observed which have
      been assigned on the basis of UCCSD(T)-F12/VQZ-F12 and IP-EOM CCSD calculations.
      Vibrational structure has only been resolved in the TPE spectrum of the first
      band, associated with the X(2)Bg H2O2(+) <- X(1)A H2O2 ionization, on its low
      energy side. This structure is assigned with the help of harmonic Franck-Condon
      factor calculations that use the UCCSD(T)-F12a/VQZ-F12 computed adiabatic
      ionization energy (AIE), and UCCSD(T)-F12a/VQZ-F12 computed equilibrium geometric
      parameters and harmonic vibrational frequencies for the H2O2 X(1)A state and the
      H2O2(+) X(2)Bg state. These calculations show that the main vibrational structure
      on the leading edge of the first TPE band is in the O-O stretching mode (omega3)
      and the HOOH deformation mode (omega4), and comparison of the simulated spectrum
      to the experimental spectrum gives the first AIE of H2O2 as (10.685 +/- 0.005) eV
      and omega4 = (850 +/- 30) and omega3 = (1340 +/- 30) cm(-1) in the X(2)Bg state
      of H2O2(+). Contributions from ionization of vibrationally excited levels in the
      torsion mode have been identified in the TPE spectrum of the first band and the
      need for a vibrationally resolved TPE spectrum from vibrationally cooled
      molecules, as well as higher level Franck-Condon factors than performed in this
      work, is emphasized. 

PMID- 27045949
TI  - Exploring the Mechanism of Ultrafast Intersystem Crossing in Rhenium(I) Carbonyl
      Bipyridine Halide Complexes: Key Vibrational Modes and Spin-Vibronic Quantum
      Dynamics.
AB  - The mechanism of ultrafast intersystem crossing in rhenium(I) carbonyl bipyridine
      halide complexes Re(X)(CO)3(bpy) (X = Cl, Br, I) is studied by exploring the
      structural deformations when going from Franck-Condon (FC) to critical geometries
      in the low-lying singlet and triplet excited states and by selecting the key
      vibrational modes. The luminescent decay observed in [Re(Br)(CO)3(bpy)] is
      investigated by means of wavepacket propagations based on the multiconfiguration
      time-dependent Hartree (MCTDH) method. The dominant coordinates underlying the
      nonradiative decay process are extracted from minima, minimum energy seam of
      crossing (MESX) and minimum energy conical intersection (MECI) geometries
      obtained by the seam model function (SMF)/single-component artificial force
      induced reaction (SC-AFIR) approach. By choosing the normal modes used in MCTDH
      from the MECI and MESX geometries, not only the degenerate energy points but also
      the low-energy-gap regions are included. For this purpose a careful vibrational
      analysis is performed at each critical geometry and analyzed under the light of
      the pertinent nonadiabatic coupling terms obtained from the linear vibronic
      coupling (LVC) model augmented by spin-orbit coupling (SOC) in the electronic
      diabatic representation. 

PMID- 27045950
TI  - Orientational Dynamics of Water at an Extended Hydrophobic Interface.
AB  - We report on the orientational dynamics of water at an extended hydrophobic
      interface with an octadecylsilane self-assembled monolayer on fused silica. The
      interfacial dangling OH stretch mode is excited with a resonant pump, and its
      evolution followed in time by a surface-specific, vibrationally resonant,
      infrared-visible sum-frequency probe. High sensitivity pump-probe anisotropy
      measurements and isotopic dilution clearly reveal that the decay of the dangling
      OH stretch excitation is almost entirely due to a jump to a hydrogen-bonded
      configuration that occurs in 1.61 +/- 0.10 ps. This is more than twice as fast as
      the jump time from one hydrogen-bonded configuration to another in bulk H2O but
      about 50% slower than the reported out-of-plane reorientation at the air/water
      interface. In contrast, the intrinsic population lifetime of the dangling OH
      stretch in the absence of such jumps is found to be >10 ps. Molecular dynamics
      simulations of air/water and hexane/water interfaces reproduce the fast jump
      dynamics of interfacial dangling OH with calculated jump times of 1.4 and 1.7 ps
      for the air and hydrophobic interfaces, respectively. The simulations highlight
      that while the air/water and hydrophobic/water surfaces exhibit great structural
      similarities, a small stabilization of the OH groups by the hydrophobic interface
      produces the pronounced difference in the dynamics of dangling bonds.

PMID- 27045951
TI  - Interlaboratory Trial for Measurement of Vitamin D and 25-Hydroxyvitamin D
      [25(OH)D] in Foods and a Dietary Supplement Using Liquid Chromatography-Mass
      Spectrometry.
AB  - Assessment of total vitamin D intake from foods and dietary supplements (DSs) may
      be incomplete if 25-hydroxyvitamin D [25(OH)D] intake is not included. However,
      25(OH)D data for such intake assessments are lacking, no food or DS reference
      materials (RMs) are available, and comparison of laboratory performance has been
      needed. The primary goal of this study was to evaluate whether vitamin D3 and
      25(OH)D3 concentrations in food and DS materials could be measured with
      acceptable reproducibility. Five experienced laboratories from the United States
      and other countries participated, all using liquid chromatography tandem-mass
      spectrometry but no common analytical protocol; however, various methods were
      used for determining vitamin D3 in the DS. Five animal-based materials (including
      three commercially available RMs) and one DS were analyzed. Reproducibility
      results for the materials were acceptable. Thus, it is possible to obtain
      consistent results among experienced laboratories for vitamin D3 and 25(OH)D3 in
      foods and a DS. 

PMID- 27045952
TI  - Correlation between different markers for the assessment of red chilli pepper
      powders stability during shelf-life.
AB  - Pungency and red colour of Capsicum powders deteriorate during processing and
      storage, resulting in a decrease in market value. Two varieties of pepper with
      different pungencies were monitored for capsaicinoids, colour and furosine.
      Aliquots were stored at room and at low temperature during one year. At low
      temperature all indicators were stable in both varieties, while at room
      temperature, redness and capsacinoids decreased significantly, while furosine
      increased. High correlation was found between those markers. The more pungent
      variety exhibited higher stability in terms of all parameters. Differences
      observed suggest a potential protective effect exerted by capsaicinoids on powder
      stability. The decrease in capsaicinoids and redness accompanied by furosine
      increase showed a linkage between those markers never reported before.
      Considering that capsaicinoids and furosine occurrence have strong impact on the
      nutritional profile, the findings of this work show relevant changes in the
      nutritional value of chilli pepper powder after storage. 

PMID- 27045953
TI  - London Education and Inclusion Project (LEIP): Exploring Negative and Null
      Effects of a Cluster-Randomised School-Intervention to Reduce School Exclusion-
      Findings from Protocol-Based Subgroup Analyses.
AB  - This paper presents subgroup analyses from the London Education and Inclusion
      Project (LEIP). LEIP was a cluster-randomised controlled trial of an intervention
      called Engage in Education-London (EiE-L) which aimed to reduce school exclusions
      in those at greatest risk of exclusion. Pupils in the control schools attended an
      hour-long employability seminar. Minimisation was used to randomly assign schools
      to treatment and control following baseline data collection. The study involved
      36 schools (17 in treatment--373 pupils; 19 in control--369 pupils) with >28%
      free school meal eligibility across London and utilised on pupil self-reports,
      teacher reports as well as official records to assess the effectiveness of EiE-L.
      Due to multiple data sources, sample sizes varied according to analysis. Analyses
      of pre-specified subgroups revealed null and negative effects on school exclusion
      following the intervention. Our findings suggest that the design and
      implementation of EiE-L may have contributed to the negative outcomes for pupils
      in the treatment schools when compared to those in the control schools. These
      findings call into question the effectiveness of bolt-on short-term interventions
      with pupils, particularly those at the highest risk of school exclusion and when
      they are faced with multiple problems. This is especially pertinent given the
      possibility of negative outcomes. TRIAL REGISTRATION: Controlled Trials:
      ISRCTN23244695.

PMID- 27045954
TI  - Behavioural But Not Cognitive Impairment Is a Determinant of Caregiver Burden in
      Amyotrophic Lateral Sclerosis.
AB  - BACKGROUND: Caregivers of patients affected by amyotrophic lateral sclerosis
      (ALS) are involved with great determination in the treatment process since the
      earliest stages of the disease with an increasing burden to be of help to the
      ailing persons. AIM: To test separately the impact of ALS patients' cognitive and
      behavioural impairments on caregiver burden and mood status in 84 outpatient/main
      caregiver couples. DESIGN: Patients were tested with the ALS-Cognitive
      Behavioural Screen (ALSCBS-ci and -bi), Frontal Assessment Battery, Weigl's
      Sorting Test, Mini-Mental State Examination, Beck's Depression Inventory (BDI).
      Analogously, caregivers completed the BDI and Caregiver Burden Inventory (CBI).
      RESULTS: CBI correlated with ALSCBS-bi, besides ALSFRS-R, disease progression
      index and caregiver BDI. Caregiver BDI also correlated with ALSCBS-bi scores. No
      correlations were found with cognitive tests. The correlation between CBI and the
      ALSCBS-bi score was specifically sustained by the social burden sub-domain of
      CBI. CONCLUSIONS: As previously reported using other tools, behavioural
      impairment is a determinant of burden and mood in ALS caregivers. Conversely,
      cognitive impairment fails to emerge as a major target when aiming at easing the
      increasing burden or improving mood in ALS caregivers.

PMID- 27045956
TI  - Is Shape of a Fresh and Dried Leaf the Same?
AB  - Plants kept as dried herbarium specimens share many characteristics with their
      living counterparts, but there are some substantial differences between them. Due
      to dehydration, leaves of herbarium specimens change not only their mass and
      colour, but in many cases change their dimensions, too. The present study aimed
      to determine whether leaf shape changes during the drying process. A total of 794
      pairs of fresh and dried leaves or leaflets of 22 plant taxa were studied. The
      shape of the blades was quantified using elliptic Fourier analysis combined with
      principal component analysis. In addition, area and mass of the leaves were
      measured. Statistical tests were applied for comparing fresh and dried leaves.
      The results indicate that the preservation process of pressing and drying plants
      for herbarium purposes causes changes in leaf shape. In general, the shape
      changes were directional. As the shape of fresh and dried plants is different, it
      is strongly recommended that shape analyses should be performed on datasets
      containing either of the leaf types. 

PMID- 27045955
TI  - Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.
AB  - During a survey of clinical rectal prolapse (RP) cases in the mouse population at
      MIT animal research facilities, a high incidence of RP in the lamellipodin knock
      out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further
      investigation, the Lpd-/- colony was found to be infected with multiple endemic
      enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain
      produced at MIT, have not previously shown a distinct immune phenotype and are
      not highly susceptible to other opportunistic infections. Predominantly male Lpd
      /- mice with RP exhibited lesions consistent with invasive rectal carcinoma
      concomitant to clinically evident RP. Multiple inflammatory cytokines, CD11b+Gr1+
      myeloid-derived suppressor cell (MDSC) populations, and epithelial cells positive
      for a DNA damage biomarker, H2AX, were elevated in affected tissue, supporting
      their role in the neoplastic process. An evaluation of Lpd-/- mice with RP
      compared to EHS-infected, but clinically normal (CN) Lpd-/- animals indicated
      that all of these mice exhibit some degree of lower bowel inflammation; however,
      mice with prolapses had significantly higher degree of focal lesions at the colo
      rectal junction. When Helicobacter spp. infections were eliminated in Lpd-/- mice
      by embryo transfer rederivation, the disease phenotype was abrogated, implicating
      EHS as a contributing factor in the development of rectal carcinoma. Here we
      describe lesions in Lpd-/- male mice consistent with a focal inflammation-induced
      neoplastic transformation and propose this strain as a mouse model of rectal
      carcinoma. 

PMID- 27045957
TI  - Pseudorhodobacter sinensis sp. nov. and Pseudorhodobacter aquaticus sp. nov.,
      isolated from crater lakes.
AB  - Three Gram-stain negative, aerobic, non-motile, rod-shaped bacterial strains,
      Y1R2-4T, Y3R2-3 and DC2N1-10T, isolated from two crater lakes of the Daxinganling
      Mountains, northern China, were studied to determine their taxonomic position.
      They grew at 4-30  degrees C (optimally at 20-25  degrees C), at pH 6.0-7.5
      (optimally at pH 7.0) and in the presence of 0-0.5 % (w/v) NaCl. On the basis of
      16S rRNA gene sequence analysis, these strains showed 95.3-96.6 % similarity to
      members of the genus Pseudorhodobacter, including Pseudorhodobacter ferrugineus
      DSM 5888T, Pseudorhodobacter wandonensis WT-MW11T, Pseudorhodobacter antarcticus
      ZS3-33T and Pseudorhodobacter aquimaris HDW-19T. All strains contained Q-10 as
      the predominant ubiquinone and C18 : 1omega7c as the major fatty acid. The main
      polar lipids for strains Y1R2-4T and Y3R2-3 were phosphatidylglycerol,
      phosphatidylcholine, one unidentified aminophospholipid, one unidentified
      aminolipid, three unidentified phospholipids and two unidentified lipids, and
      those for strain DC2N1-10T were phosphatidylglycerol, phosphatidylcholine, one
      unidentified aminophospholipid, one unidentified aminolipid, one unidentified
      phospholipid and several unidentified lipids. The DNA G+C contents of strains
      Y1R2-4T, Y3R2-3 and DC2N1-10T were 61.9, 61.0 and 60.0 mol%, respectively. In
      addition, strain Y1R2-4T shared less than 50 % DNA-DNA relatedness to strain
      DC2N1-10T. Based on these differences in genetic, physiological and
      chemotaxonomic properties, strains Y1R2-4T, Y3R2-3 and DC2N1-10T were considered
      to represent two novel species of the genus Pseudorhodobacter, for which the
      names Pseudorhodobacter sinensis sp. nov. (type strain Y1R2-4T=CGMCC1.14435T=KCTC
      52039T) and Pseudorhodobacter aquaticus sp. nov. (type strain DC2N1
      10T=CGMCC1.14433T=KCTC 52040T) are proposed. 

PMID- 27045958
TI  - Predictive Value of Carotid Distensibility Coefficient for Cardiovascular
      Diseases and All-Cause Mortality: A Meta-Analysis.
AB  - AIMS: The aim of the present study is to determine the pooled predictive value of
      carotid distensibility coefficient (DC) for cardiovascular (CV) diseases and all
      cause mortality. BACKGROUND: Arterial stiffness is associated with future CV
      events. Aortic pulse wave velocity is a commonly used predictor for CV diseases
      and all-cause mortality; however, its assessment requires specific devices and is
      not always applicable in all patients. In addition to the aortic artery, the
      carotid artery is also susceptible to atherosclerosis, and is highly accessible
      because of the surficial property. Thus, carotid DC, which indicates the
      intrinsic local stiffness of the carotid artery and may be determined using
      ultrasound and magnetic resonance imaging, is of interest for the prediction.
      However, the role of carotid DC in the prediction of CV diseases and all-cause
      mortality has not been thoroughly characterized, and the pooled predictive value
      of carotid DC remains unclear. METHODS: A meta-analysis, which included 11
      longitudinal studies with 20361 subjects, was performed. RESULTS: Carotid DC
      significantly predicted future total CV events, CV mortality and all-cause
      mortality. The pooled risk ratios (RRs) of CV events, CV mortality and all-cause
      mortality were 1.19 (1.06-1.35, 95%CI, 9 studies with 18993 subjects), 1.09 (1.01
      1.18, 95%CI, 2 studies with 2550 subjects) and 1.65 (1.15-2.37, 95%CI, 6 studies
      with 3619 subjects), respectively, for the subjects who had the lowest quartile
      of DC compared with their counterparts who had higher quartiles. For CV events,
      CV mortality and all-cause mortality, a decrease in DC of 1 SD increased the risk
      by 13%, 6% and 41% respectively, whereas a decrease in DC of 1 unit increased the
      risk by 3%, 1% and 6% respectively. CONCLUSIONS: Carotid DC is a significant
      predictor of future CV diseases and all-cause mortality, which may facilitate the
      identification of high-risk patients for the early diagnosis and prompt treatment
      of CV diseases.

PMID- 27045959
TI  - Born-Oppenheimer Molecular Dynamics Study on Proton Dynamics of Strong Hydrogen
      Bonds in Aspirin Crystals, with Emphasis on Differences between Two Crystal
      Forms.
AB  - In this study, the proton dynamics of hydrogen bonds for two forms of crystalline
      aspirin was investigated by the Born-Oppenheimer molecular dynamics (BOMD)
      method. Analysis of the geometrical parameters of hydrogen bonds using BOMD
      reveals significant differences in hydrogen bonding between the two crystalline
      forms of aspirin, Form I and Form II. Analysis of the trajectory for Form I shows
      spontaneous proton transfer in cyclic dimers, which is absent in Form II.
      Quantization of the O-H stretching modes allows a detailed discussion on the
      strength of hydrogen-bonding interactions. The focal point of our study is
      examination of the hydrogen bond characteristics in the crystal structure and
      clarification of the influence of hydrogen bonding on the presence of the two
      crystalline forms of aspirin. In the BOMD method, thermal motions were taken into
      account. Solving the Schrodinger equation for the snapshots of 2D proton
      potentials, extracted from MD, gives the best agreement with IR spectra. The
      character of medium-strong hydrogen bonds in Form I of aspirin was compared with
      that of weaker hydrogen bonds in aspirin Form II. Two proton minima are present
      in the potential function for the hydrogen bonds in Form I. The band contours,
      calculated by using one- and two-dimensional O-H quantization, reflect the
      differences in the hydrogen bond strengths between the two crystalline forms of
      aspirin, as well as the strong hydrogen bonding in the cyclic dimers of Form I
      and the medium-strong hydrogen bonding in Form II.

PMID- 27045960
TI  - Indices for the assessment of nutritional quality of meals: a systematic review.
AB  - This systematic review aimed to synthesise information on indices developed to
      evaluate nutritional quality of meals. A strategy for systematic search of the
      literature was developed using keywords related to assessment of meal quality.
      Databases searched included ScienceDirect, PubMed, Lilacs, SciELO, Scopus,
      Cochrane, Embase and Google Scholar. The literature search resulted in seven
      different meal quality indices. Each article was analysed in order to identify
      the following items: authors, country, year, study design, population
      characteristics, type of meal evaluated, dietary assessment method,
      characteristics evaluated (nutrients or food items), score range, index
      components, nutritional references, correlations performed, validation and
      relationship with an outcome (if existing). Two studies developed instruments to
      assess the quality of breakfast, three analysed lunch, one evaluated dinner and
      one was applied to all types of meals and snacks. All meal quality indices
      reviewed were based on the evaluation of presence or absence of food groups and
      relative contributions of nutrients, according to food-based guidelines or
      nutrient references, adapting the daily dietary recommendations to one specific
      meal. Most of the indices included three items as components for meal quality
      assessment: (I) total fat or some specific type of fat, (II) fruits and
      vegetables and (III) cereals or whole grains. This systematic review indicates
      aspects that need further research, particularly the numerous approaches to
      assessing meals considering different foods and nutrients, and the need for
      validation studies of meal indices.

PMID- 27045961
TI  - Determining sensitivity/specificity of virtual reality-based neuropsychological
      tool for detecting residual abnormalities following sport-related concussion.
AB  - OBJECTIVE: Computer-based neuropsychological (NP) evaluation is an effective
      clinical tool used to assess cognitive function which complements the clinical
      diagnosis of a concussion. However, some researchers and clinicians argue its
      lack of ecological validity places limitations on externalizing results to a
      sensory rich athletic environment. Virtual reality-based NP assessment offers
      clinical advantages using an immersive environment and evaluating domains not
      typically assessed by traditional NP assessments. The sensitivity and specificity
      of detecting lingering cognitive abnormalities was examined on components of a
      virtual reality-based NP assessment battery to cohort affiliation (concussed vs.
      controls). METHOD: Data were retrospectively gathered on 128 controls (no
      concussion) and 24 concussed college-age athletes on measures of spatial
      navigation, whole body reaction, attention, and balance in a virtual environment.
      Concussed athletes were tested within 10 days (M = 8.33, SD = 1.06) of concussion
      and were clinically asymptomatic at the time of testing. RESULTS: A priori alpha
      level was set at 0.05 for all tests. Spatial navigation (sensitivity
      95.8%/specificity 91.4%, d = 1.89), whole body reaction time (sensitivity
      95.2%/specificity 89.1%, d = 1.50) and combined virtual reality modules
      (sensitivity 95.8%,/specificity 96.1%, d = 3.59) produced high
      sensitivity/specificity values when determining performance-based variability
      between groups. CONCLUSIONS: Use of a virtual reality-based NP platform can
      detect lingering cognitive abnormalities resulting from concussion in clinically
      asymptomatic participants. Virtual reality NP platforms may compliment the
      traditional concussion assessment battery by providing novel information.
      (PsycINFO Database Record

PMID- 27045962
TI  - [Diagnostic and therapeutic approach to cervical paragangliomas in geriatrics].

PMID- 27045963
TI  - Correction: A Model-Based Joint Identification of Differentially Expressed Genes
      and Phenotype-Associated Genes.

PMID- 27045964
TI  - Zerumbone, a Sesquiterpene, Controls Proliferation and Induces Cell Cycle Arrest
      in Human Laryngeal Carcinoma Cell Line Hep-2.
AB  - Zerumbone (ZER), a sesquiterpene found in Zingiber zerumbet Smith, has been shown
      to possess antiproliferative, anticancer, antioxidant, and anti-inflammatory
      activity against various types of human carcinoma. The molecular mechanism by
      which ZER mediates its activity against many cancer types is revealed by many
      studies. Upregulation of proapoptotic molecules and suppression of antiapoptotic
      gene expression are few of the mechanisms by which ZER mediates its effect. The
      present study is focused on investigating the effect of ZER on proliferation of
      laryngeal carcinoma cells (Hep-2). MTT assay results showed that ZER (0.01-100
      MUM) induced death of Hep-2 cells in a concentration-dependent manner;
      significant suppression of proliferation of Hep-2 cells was seen with a IC50
      value of 15 uM. ZER at a concentration of 15 and 30 MUM for 48 h showed early
      signs of apoptosis as evidenced by confocal microscopy imaging. Flow cytometry
      studies showed that ZER induced cell cycle arrest. ZER arrested Hep-2
      proliferation at S and G2/M phases of cell cycle. In conclusion, these results
      indicate that ZER has antiproliferative effect and arrests cell cycle in Hep-2
      cells in vitro. This could be a potential anticancer drug against laryngeal
      carcinoma.

PMID- 27045965
TI  - Have we overcome choline PET/CT for early detection of prostate cancer
      recurrence?

PMID- 27045966
TI  - The role of emotion regulation in childhood obesity: implications for prevention
      and treatment.
AB  - Stress and negative emotions pose a major threat to public health, by increasing
      the risk of obesity. Since the management process for emotions (emotion
      regulation; ER) is developed in childhood, we present a novel conceptual
      framework model for the role of ER in the prevention and treatment of childhood
      obesity. A narrative review of the literature by electronic database search
      (MEDLINE, Web of Knowledge and Scopus) was conducted of observational and
      interventional/experimental literature on ER and obesity and the underlying
      concepts. We also present an overview of ER intervention techniques. Our model
      indicates that childhood ER is a link between stress and obesity. Stress along
      with ineffective ER leads to abnormal cortisol patterns, emotional eating,
      sedentary lifestyle, reduction of physical activity, and sleep problems.
      Simultaneously, a healthy lifestyle could show benefits on ER and in developing
      adaptive ER strategies. In the development of obesity and ER, parents also play a
      role. By contrast, effective ER skills decrease obesity-related unhealthy
      behaviour and enhance protective factors, which boost health. The literature
      contains some observational studies of children but very few intervention
      studies, most of which are pilot or on-going studies. In conclusion, encouraging
      effective ER could be a useful new approach for combating and treating childhood
      obesity. Future ER intervention studies are needed to confirm the validity of
      this model in children. 

PMID- 27045967
TI  - Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory
      Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival.
AB  - Mortality due to refractory cardiogenic shock (RCS) exceeds 50%. Venoarterial
      extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for
      RCS. The aim of our study was to evaluate outcomes of patients with RCS treated
      with percutaneous VA-ECMO (pVA-ECMO). Retrospective review of patients supported
      with VA-ECMO at our institution in 2012-2013. Clinical characteristics, bleeding,
      vascular complications, and outcomes including survival were assessed. A total of
      37 patients were supported with VA-ECMO for RCS. The majority of VA-ECMO (76%)
      was placed in the catheterization laboratory. Nearly half (49%) of the patients
      presented with acute myocardial infarction. Seven patients (19%) underwent
      insertion of pVA-ECMO in the setting of cardiopulmonary resuscitation with
      mechanical chest compression device. Median duration of support was 5 days. Index
      hospitalization, 30-day, and 1-year survival were 65%, 65%, and 57%,
      respectively. Survival rate for discharged patients was 87.5% with a median
      follow-up of 450 days. Refractory cardiogenic shock supported with pVA-ECMO is
      associated with an improved survival in patients with a traditionally poor
      prognosis.

PMID- 27045968
TI  - Acute Embolic Myocardial Infarction and Heart Failure in a Fontan Patient:
      Recovery with Impella Device and Successful Transplantation.
AB  - Patients with Fontan palliation are at a higher risk of thromboembolic events, as
      well as sudden death. We report a case of acute thromboembolic myocardial
      infarction in a patient with Fontan circulation, presenting with acute heart
      failure. Coronary thrombolysis and reperfusion did not improve the myocardial
      dysfunction and warranted a unique application of mechanical support with Impella
      2.5 pump as a bridge to decision. The patient was successfully transplanted. The
      case highlights the thromboembolic risks and provides support for the early use
      of mechanical support in such scenarios, even in single ventricle patients.

PMID- 27045969
TI  - Single-Site Low-Flow Veno-Venous Extracorporeal Lung Support Does Not Influence
      Hemodynamic Monitoring by Transpulmonary Thermodilution.
AB  - The application of extracorporeal lung support (ECLS) in patients with acute
      respiratory distress syndrome is a well-established concept. In patients
      receiving ECLS therapy, hemodynamic monitoring is often required. However, less
      is known about the effect of ECLS on hemodynamic measurements. In the present
      work, the influence of single-site low-flow veno-venous ECLS (LFVV-ECLS) on
      hemodynamic monitoring by transpulmonary thermodilution (TPTD) was prospectively
      investigated. Five consecutive patients undergoing single-site LFVV-ECLS for
      severe hypercapnic respiratory failure were included in this study. For single
      site LFVV-ECLS, a 22 Fr twin-port double-lumen cannula was inserted
      percutaneously into the right jugular vein. Hemodynamic monitoring was performed
      using the Pulse index Continuous Cardiac Output system. Before ECLS initiation,
      baseline measurements of cardiac index, systemic vascular resistance, mean
      arterial pressure, and extravascular lung water (EVLW) were performed. During the
      first 3 days of ECLS therapy, repeated hemodynamic measurements at different ECLS
      flow rates were performed. No significant differences were seen in hemodynamic
      measurements. With respect to EVLW, a significant decrease over the duration of
      ECLS therapy was observed. This study demonstrates that LFVV-ECLS does not
      interfere with TPTD. It needs to be further studied if these findings also apply
      to other ECLS modes.

PMID- 27045970
TI  - New Dual Lumen Self-Expanding Catheter Design Requiring Less Suction.
AB  - Contribution of venovenous extracorporeal membrane oxygenation (v-v ECMO) to gas
      transfer is flow dependent. Catheter design is a key factor for optimal
      pressure/flow rate relationship. This study was designed for the assessment of a
      new self-expanding dual lumen catheter design versus the current standard. Outlet
      pressure/flow rate and inlet pressure/flow rate for a new Smart catheter with
      self-expanding dual lumen design constricted to 27 F with 5 mm long constrictor
      corresponding to the percutaneous path versus Avalon 27 F catheter (control) were
      compared on a flow bench with a Biomedicus centrifugal pump. Flow, pump inlet
      pressure and outlet pressure were determined at 500, 1,000, 1,500, 2,000, and
      2,500 revolutions per minute (RPM). At 500 RPM and with a 5 mm long constrictor
      (1,000; 1,500; 2,000; and 2,500 RPM), catheter outlet pressure values were -0.13
      +/- 0.07 mm Hg (-2.55 +/- 0.06; -7.38 +/- 0.14; -15.03 +/- 0.44; -26.46 +/- 0.39)
      for self-expanding versus -2.93 +/- 0.23* (-10.60 +/- 0.14; -22.74 +/- 0.34; 
      38.43 +/- 0.41; -58.25 +/- 0.40)*: p < 0.0001* for control. The flow values were
      0.61 +/- 0.01 L/min (1.64 +/- 0.03, 2.78 +/- 0.02; 4.07 +/- 0.04; 5.37 +/- 0.02)
      for self-expanding versus 1.13 +/- 0.06*; (2.19 +/- 0.04; 3.30 +/- 0.03; 4.30 +/-
      0.03; 5.30 +/- 0.03)*: p < 0.0001* for control. The corresponding catheter inlet
      flow rates of the self-expanding catheter were slightly more than that of the
      control. For the given setup, our evaluation demonstrated that the new dual lumen
      self-expanding catheter requires lower catheter outlet pressures for higher flows
      as compared to the current standard.

PMID- 27045971
TI  - Effects of Piper sarmentosum extract on the growth performance, antioxidant
      capability and immune response in weaned piglets.
AB  - The biological properties of Piper sarmentosum render it a potential substitute
      for antibiotics in livestock feed. This study evaluated the effects of P.
      sarmentosum extract (PSE) on the growth performance, antioxidant capability and
      immune response of weaned piglets. Eighty 21-d-old weaned piglets were selected
      and randomly allocated to one of four dietary treatments with five replicates of
      four pigs each. The dietary treatments consisted of a basal diet supplemented
      with 0 (T0), 50 (T50), 100 (T100) or 200 (T200) mg/kg PSE. The feeding trial
      lasted 4 weeks. The results revealed that the T50 group had the highest average
      daily gain (ADG) and average daily feed intake (ADFI) throughout the feeding
      trial (p < 0.05). Additionally, the T50 group had higher (p < 0.05) serum
      glutathione peroxidase activity (GSH-Px) and lower (p < 0.05) serum
      malondialdehyde (MDA) levels than the T0 group at 4 weeks post-weaning (p <
      0.05). Serum levels of interleukin-1beta (IL-1beta) and tumour necrosis factor
      alpha (TNF-alpha) decreased, while serum levels of interleukin-4 (IL-4),
      interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) increased
      by PSE supplementation at 4 weeks post-weaning (p < 0.05). PSE supplementation
      upregulated the mRNA expression of IL-4, IL-10 and TGF-beta and downregulated the
      mRNA expression of TNF-alpha, IL-1beta and interleukin-6 (IL-6) in the ileal
      mucosal layer of piglets (p < 0.05). In summary, our study findings revealed that
      PSE supplementation improved the antioxidant capability, and reduced
      inflammation, which may be beneficial to weaned piglet health.

PMID- 27045972
TI  - Two-Photon Small Molecule Enzymatic Probes.
AB  - Enzymes are essential for life, especially in the development of disease and on
      drug effects, but as we cannot yet directly observe the inside interactions and
      only partially observe biochemical outcomes, tools "translating" these processes
      into readable information are essential for better understanding of enzymes as
      well as for developing effective tools to fight against diseases. Therefore,
      sensitive small molecule probes suitable for direct in vivo monitoring of enzyme
      activities are ultimately desirable. For fulfilling this desire, two-photon small
      molecule enzymatic probes (TSMEPs) producing amplified fluorescent signals based
      on enzymatic conversion with better photophysical properties and deeper
      penetration in intact tissues and whole animals have been developed and
      demonstrated to be powerful in addressing the issues described above.
      Nonetheless, currently available TSMEPs only cover a small portion of enzymes
      despite the distinct advantages of two-photon fluorescence microscopy. In this
      Account, we would like to share design principles for TSMEPs as potential
      indicators of certain pathology-related biomarkers together with their
      applications in disease models to inspire more elegant work to be done in this
      area. Highlights will be addressed on how to equip two-photon fluorescent probes
      with features amenable for direct assessment of enzyme activities in complex
      pathological environments. We give three recent examples from our laboratory and
      collaborations in which TSMEPs are applied to visualize the distribution and
      activity of enzymes at cellular and organism levels. The first example shows that
      we could distinguish endogenous phosphatase activity in different organelles; the
      second illustrates that TSMEP is suitable for specific and sensitive detection of
      a potential Parkinson's disease marker (monoamine oxidase B) in a variety of
      biological systems from cells to patient samples, and the third identifies that
      TSMEPs can be applied to other enzyme families (proteases). Indeed, TSMEPs have
      helped to uncover new biological roles and functions of a series of enzymes;
      therefore, we hope to encourage more TSMEPs to be developed for diverse enzymes.
      Meanwhile, improvements in the TSMEP properties (such as new two-photon
      fluorophores with longer excitation and emission wavelengths and strategies
      allowing high specificity) are also indispensable for producing high-fidelity
      information inside biological systems. We are enthusiastic however that, with
      these efforts and wider applications of TSMEPs in both research studies and
      further clinical diagnoses, comprehensive knowledge of enzyme contributions to
      various physiologies will be obtained. 

PMID- 27045973
TI  - Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased
      plant productivity on fox dens.
AB  - Top predators can provide fundamental ecosystem services such as nutrient
      cycling, and their impact can be even greater in environments with low nutrients
      and productivity, such as Arctic tundra. We estimated the effects of Arctic fox
      (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near
      Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher
      nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable
      phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable
      phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased
      from June to August on both dens and controls, whereas extractable phosphorous
      increased. Pup production the previous year, which should enhance nutrient
      deposition (from urine, feces, and decomposing prey), did not affect soil
      nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year.
      Dens supported 2.8 times greater vegetation biomass in August, but delta(15)N
      values in sea lyme grass (Leymus mollis) were unaffected by denning. By
      concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an
      ecosystem service and thus engineer Arctic ecosystems on local scales. The
      enhanced productivity in patches on the landscape could subsequently affect plant
      diversity and the dispersion of herbivores on the tundra. 

PMID- 27045974
TI  - Assessment of health status by molecular measures in adults ranging from middle
      aged to old: Ready for clinical use?
AB  - In addition to measures already used in clinical practice, molecular measures
      have been proposed to assess health status, but these have not yet been
      introduced into clinical practice. We aimed to test the association of functional
      capacity measures used in current practice and molecular measures with age and
      health status. The cohort consisted of 178 middle-aged to old participants of the
      Leiden Longevity Study (range 42-82years). We tested associations between
      functional capacity measures (physical tests: grip strength, 4-meter walk, chair
      stand test; cognitive tests: Stroop test, digit symbol substitution test and 15
      picture learning test) with age and with cardiovascular or metabolic disease as a
      measure of the health status. These associations with age and health status were
      also tested for molecular measures (C reactive protein (CRP), numbers of
      senescent p16INK4a positive cells in the epidermis and dermis and putative
      immunosenescence (presence of CD57+ T cells)). All functional capacity measures
      were associated with age. CRP and epidermal p16INK4a positivity were also
      associated with age, but with smaller estimates. Grip strength and the Stroop
      test were associated with cardiovascular or metabolic disease, as was epidermal
      p16INK4a positivity. All associations with cardiovascular or metabolic disease
      attenuated when adjusting for age. In conclusion, in middle-aged to old persons,
      the molecular measures tested here were more weakly associated with age and
      health status than functional capacity measures. Whether these molecular measures
      associate more closely with health status in the elderly or in specific groups of
      patients needs to be explored further.

PMID- 27045975
TI  - Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.
AB  - Notch is a key player in various developmental processes during the embryonic
      stage as well as in regulating tissue homeostasis, cell differentiation, and stem
      cell maintenance in adult life. Activation of Notch signaling occurs following
      Notch receptor-ligand interaction and subsequent enzymatic proteolysis by the
      gamma-secretase complex, resulting in the cytoplasmic release of a Notch
      intracellular domain, which translocates to the nucleus to initiate the
      downstream transcriptional machinery. Notch activation and its aberrant signaling
      have been broadly linked to the pathogenesis of cancer and some chronic
      inflammatory diseases resulting in pathologic fibrotic processes. This review
      focuses on the molecular basis of Notch-induced signaling and its interaction
      with other pathways to identify therapeutic targets. We also highlight current
      efforts to pharmacologically intervene in Notch signaling and discuss promising
      ongoing experimental and clinical studies.

PMID- 27045976
TI  - Efficacy of psychosocial interventions on psychological outcomes among people
      with cardiovascular diseases: a systematic review and meta-analysis.
AB  - OBJECTIVES: This systematic review aimed to examine empirical evidence concerning
      the efficacy of psychosocial interventions in ameliorating the psychosocial
      problems of people with cardiovascular diseases (CVDs). METHODS: A comprehensive
      literature search was undertaken to identify both published and non-published
      English randomised controlled trials (RCTs) from 2000 to 2015. Two reviewers
      independently screened, assessed risks for bias, and extracted data.
      Comprehensive meta-analysis software was used to analyse the extracted data.
      Hedges's g effect size was used to determine the effects of psychosocial
      interventions. RESULTS: Thirty studies were included in the review but only 18
      studies reported significant short-term effects of psychosocial interventions in
      CVD patients. Most studies did not report long-term effects. Average effect sizes
      for stress, anxiety, depression, and combined depression/anxiety were 0.34, 1.04,
      0.42 and 0.67 respectively at post-tests. Those numbers became 0.09, 0.65, 0.22
      and 0.09 at follow-up assessments. Psychosocial programmes with psychoeducation
      and stress management helped reduce patients' stress and anxiety levels.
      Programmes including psychotherapy, counselling, mindfulness-based intervention
      (MBI), and stress management helped mitigate depression and anxiety. CONCLUSIONS:
      The findings support the efficacy of some psychosocial interventions in people
      with CVDs. PRACTICE IMPLICATIONS: Healthcare providers should monitor patients'
      psychological problems and may integrate psychosocial interventions as part of
      treatment plans.

PMID- 27045977
TI  - Failure pattern and salvage treatment after radical treatment of head and neck
      cancer.
AB  - Purpose The aim of the study was to test the hypothesis that head and neck cancer
      (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures
      timely detection of relapses for successful salvage treatment. This was done by
      evaluation of the pattern of failure, the temporal distribution of recurrences,
      and the outcome of salvage treatment in a contemporary cohort of HNC patients.
      Methods The study evaluated a cohort of 2062 consecutive patients treated with
      curative intent at Aarhus University Hospital from 1 January 2000 to 31 December
      2013. The database of DAHANCA contained recordings of recurrent disease in 567
      patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity,
      paranasal sinuses and salivary glands. A review of medical records was performed
      in order to update and supplement the database. Results Failures of the 567
      patients were primarily in T-site (65%) followed by N-site (36%) and M-site
      (22%). The vast majority of the first recurrences occurred within the first years
      after primary treatment; 62%, 82%, and 91% within the first, second and third
      year, respectively. Totally, 51% were amenable for salvage treatment, and 44%
      benefited from salvage in terms of a complete response. Permanent tumor control
      was observed in 128 patients (23%) after one or two salvage attempts. The highest
      salvage rate was recorded in patients with primary glottic carcinoma (41%) and
      the lowest among hypopharyngeal cancers (2%). Asymptomatic recurrence was
      recorded in 12% of all recurrences and this was found to be a positive prognostic
      factor for disease-specific survival, as they had significantly better outcome
      after salvage. Conclusion Our data support the usefulness of specialized FU in
      terms of early detection of recurrent disease. In particular patients with silent
      recurrences benefited from early detection, as they had a significantly lower
      risk ratio of death from primary HNC. 

PMID- 27045978
TI  - Mutational analysis of 33 autosomal short tandem repeat (STR) loci in southwest
      Chinese Han population based on trio parentage testing.
AB  - Mutation rates and 95% CI of 33 short tandem repeat (STR) loci (D1S2142, D2S1338,
      D2S441, D3S1358, D3S1754, D5S818, D6S1043, D7S3048, D7S820, D8S1132, D8S1179,
      D10S1248, D11S2368, D12S391, D13S1492, D13S317, D13S325, D14S306, D15S659,
      D16S539, D18S1364, D18S51, D19S433, D20S161, D21S11, D22GATA198B05, CSF1PO, FGA,
      Penta D, Penta E, TH01, TPOX, and vWA) were investigated through more than
      424,000 parent-child meiotic transfers obtained from 10636 trios parentage
      testing cases in southwest Chinese Han population. Overall, 297, including 292
      single-step, 4 double-step and 1 triple-step mutation events were observed. The
      average mutation rate was 0.70*10(-3). Most of the locus-specific mutation rates
      (varied from 0.20*10(-3) to 1.96*10(-3)) were lower than the other datasets
      (p<0.05). Mutations of 7 loci are reported for the first time. Mutation rates
      varied with population from different ethnicities and geographical regions. There
      was no significant difference between mutation expansion and contraction
      (~1.04:1). Paternal origin mutations occurred more frequently than maternal
      origin ones (~5.02:1). In addition, mutation rates indicated positive correlation
      with the expected heterozygosity (He) and geometric mean of longest run of
      perfect repeats (LRPR), respectively. Short alleles showed a trend toward
      mutation gain while long alleles trended toward mutation loss. A credible
      forensic dataset for locus-specific mutation rates of 33 loci has been
      established based upon strict inclusion criteria of large-sized parents/child
      trio cases.

PMID- 27045979
TI  - Prospects and progress of antibody-drug conjugates in solid tumor therapies.
AB  - INTRODUCTION: Antibody-drug conjugates (ADCs) for targeted chemotherapy have
      evolved in the past 2-3 decades to become a validated clinical cancer therapy
      modality. While considerable strides have been made in treating hematological
      tumors, challenges remain in the more difficult-to-treat solid cancers. AREAS
      COVERED: The current model for a successful ADC uses a highly potent cytotoxic
      drug as the payload, with stringent linker requirements and limited
      substitutions. In solid tumor treatment, a number of ADCs have not progressed
      beyond Phase I clinical trials, indicating a need to optimize additional factors
      governing translational success. In this regard, insights from mathematical
      modeling provide a number of pointers relevant to target antigen and antibody
      selection. Together with the choice of targets, these can be expected to
      complement the gains made in ADC design towards the generation of better
      therapeutics. EXPERT OPINION: While highly potent microtubule inhibitors continue
      to dominate the current ADC landscape, there are promising data with other drugs,
      linkers, and targets that suggest a more flexible model for a successful ADC is
      evolving. Such changes will undoubtedly lead to the consideration of new targets
      and constructs to overcome some of the unique natural barriers that impede the
      delivery of cytotoxic agents in solid tumor.

PMID- 27045980
TI  - Atomic Force Microscopy of DNA-wrapped Single-walled Carbon Nanotubes in Aqueous
      Solution.
AB  - We evaluated hybrids of DNA and single-walled carbon nanotubes (SWNTs) in aqueous
      solution and in air using atomic force microscopy (AFM). Although intensive AFM
      observations of these hybrids were previously carried out for samples in air,
      this is the first report on AFM observations of these hybrids in solution. As
      expected, diameters of DNA-SWNT hybrids dramatically increased in
      tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetic acid (TE) buffer
      solution. The data suggest that DNA molecules maintain their structures even on
      the SWNT surfaces. Furthermore, we simultaneously observed single DNA-SWNT
      hybrids using three different AFM modes in air and in the TE buffer solution.
      Height value of the hybrids was largest in the solution, and lowest for the mode
      that repulsive force is expected in air. For the bare SWNT molecules, height
      differences among the three AFM modes were much lower than those of the DNA-SWNT
      hybrids. DNA molecules adsorbed on SWNT surfaces flexibly changed their
      morphology as well as DNA molecules on flat surfaces such as mica. This is
      hopeful results for biological applications of DNA-SWNT hybrids. In addition, our
      results revealed the importance of the single-molecule approach to evaluate DNA
      structures on SWNT surfaces. 

PMID- 27045981
TI  - CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and
      cancer cells using polymeric nanoparticles of salinomycin and paclitaxel.
AB  - This combinational therapy is mainly aimed for complete eradication of tumor by
      killing both cancer cells and cancer stem cells. Salinomycin (SLM) was targeted
      towards cancer stem cells whereas paclitaxel (PTX) was used to kill cancer cells.
      Drug loaded poly (lactic-co-glycolic acid) nanoparticles were prepared by
      emulsion solvent diffusion method using cationic stabilizer. Size of the
      nanoparticles (below 150nm) was determined by dynamic light scattering technique
      and transmission electron microscopy. In vitro release study confirmed the
      sustained release pattern of SLM and PTX from nanoparticles more than a month.
      Cytotoxicity studies on MCF-7 cells revealed the toxicity potential of
      nanoparticles over drug solutions. Hyaluronic acid (HA) was coated onto the
      surface of SLM nanoparticles for targeting CD44 receptors over expressed on
      cancer stem cells and they showed the highest cytotoxicity with minimum IC50 on
      breast cancer cells. Synergistic cytotoxic effect was also observed with
      combination of nanoparticles. Cell uptake studies were carried out using FITC
      loaded nanoparticles. These particles showed improved cellular uptake over FITC
      solution and HA coating further enhanced the effect by 1.5 folds. CD44 binding
      efficiency of nanoparticles was studied by staining MDA-MB-231 cells with anti
      CD44 human antibody and CD44(+) cells were enumerated using flow cytometry.
      CD44(+) cell count was drastically decreased when treated with HA coated SLM
      nanoparticles indicating their efficiency towards cancer stem cells. Combination
      of HA coated SLM nanoparticles and PTX nanoparticles showed the highest
      cytotoxicity against CD44(+) cells. Hence combinational therapy using
      conventional chemotherapeutic drug and cancer stem cell inhibitor could be a
      promising approach in overcoming cancer recurrence due to resistant cell
      population. 

PMID- 27045982
TI  - Diversity of Staphylococcus aureus strains colonizing various niches of the human
      body.
AB  - OBJECTIVES: As individuals may be colonized with multiple strains of
      Staphylococcus aureus at different body sites, the objectives of this study were
      to determine whether S. aureus polyclonal colonization exists within one body
      niche and the optimal sampling sites and culture methodology to capture the
      diversity of S. aureus strains in community-dwelling individuals. METHODS: Swabs
      were collected from the nares, axillae, and inguinal folds of 3 children with
      community-associated S. aureus infections and 11 household contacts, all with
      known S. aureus colonization. S. aureus isolates were recovered from each body
      niche using 4 culture methods and evaluated for polyclonality using phenotypic
      and genotypic strain characterization methodologies. RESULTS: Within individuals,
      the mean (range) number of phenotypes and genotypes was 2.4 (1-4) and 3.1 (1-6),
      respectively. Six (43%) and 10 (71%) participants exhibited phenotypic and
      genotypic polyclonality within one body niche, respectively. Broth enrichment
      yielded the highest analytical sensitivity for S. aureus recovery, while direct
      plating to blood agar yielded the highest genotypic strain diversity.
      CONCLUSIONS: This study revealed S. aureus polyclonality within a single body
      niche. Culture methodology and sampling sites influenced the analytical
      sensitivity of S. aureus colonization detection and the robustness of phenotypic
      and genotypic strain recovery.

PMID- 27045983
TI  - Antihyperglycemia and Antihyperlipidemia Effect of Protoberberine Alkaloids From
      Rhizoma Coptidis in HepG2 Cell and Diabetic KK-Ay Mice.
AB  - Preclinical Research Rhizoma Coptidis (RC), the root of Coptis chinensis Franch,
      a species in the genus Coptis (family Ranunculaceae), has been commonly
      prescribed for the treatment of diabetes in Chinese traditional herbal medicine
      applications. The present study is focused on the assessment of the
      antihyperglycemia and antidiabetic hyperlipidemia effect of five protoberberine
      alkaloids, berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI),
      and jatrorrhizine (JAT), separated from R. Coptidis in hepatocellular carcinoma
      HepG2 cells and diabetic KK-Ay mice. Protoberberine alkaloids are effective in
      modulating hyperglycemia and hyperlipidemia. After adding BBR and COP to culture
      medium, glucose consumption of HepG2 cells was increased. In KK-Ay mice assays,
      suppressed fasting blood glucose level and ameliorated glucose tolerance were
      observed after BBR/COP administration. After treated with berberine and
      coptisine, in the same dose of 5 ug/mL, the glucose consumption of HepG2 cells
      were promoted and, respectively, reached 96.1% and 17.6%. Body weight, food
      consumption, water intake, and urinary output of KK-Ay mice were reduced after
      treated with EPI. Serum total cholesterol and triglyceride of mice were decreased
      after treated with palmatine and jatrorrhizine. Serum high-density lipoprotein
      cholesterol of mice was increased after palmatine, jatrorrhizine, and berberine
      administrated. Moreover, hepatomegaly was attenuated in JTR-treated mice.
      Suggested that these protoberberine alkaloids from R. Coptidis have potential
      curative effect for diabetes. Drug Dev Res 77 : 163-170, 2016.   (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27045984
TI  - There be dragons: effects of unexplored religion on nurses' competence in
      spiritual care.
AB  - On ancient maps unexplored lands were simply labeled 'there be dragons'
      indicating the fear that attends the unknown. Despite three decades of
      theoretical and empirical work on spirituality in nursing, evidence still
      suggests that nurses do not feel competent to engage in spiritual care. In this
      paper I propose that one of the reasons for this is a theory-theory gap between
      religion and spirituality. Generalized anxiety about the role of religion in
      society has led to under-theorizing in nursing about religious care. As a result,
      when religion and spirituality overlap at the point of care, nurses are left
      without the substantive knowledge required for practice. Robust religious
      theorizing should include thick accounts of lived religion and integrative work
      that enables nurses to understand commonalities across religions that are
      relevant to practice. As a starting point to this integrative work, nurses can be
      introduced to the nature and lexicon of lived religion, religious perspectives on
      suffering, and religious reasoning that holds meaning and mystery in tension.
      Such an approach will better prepare them for the realities of practice where the
      complexities of spirituality and religion come to play.

PMID- 27045985
TI  - Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be
      Protective Adaptions in Ischemic CAD.
AB  - BACKGROUND: Insulin resistance, beta-cell dysfunction, and ectopic fat deposition
      have been implicated in the pathogenesis of coronary artery disease (CAD) and
      type 2 diabetes, which is common in CAD patients. We investigated whether CAD is
      an independent predictor of these metabolic abnormalities and whether this
      interaction is influenced by superimposed myocardial ischemia. METHODS AND
      RESULTS: We studied CAD patients with (n = 8) and without (n = 14) myocardial
      ischemia and eight non-CAD controls. Insulin sensitivity and secretion and
      substrate oxidation were measured during fasting and oral glucose tolerance
      testing. We used magnetic resonance imaging/spectroscopy, positron emission and
      computerized tomography to characterize CAD, cardiac function, pericardial and
      abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride
      contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism
      and a proportional decline in beta-cell insulin secretion and reduction in lipid
      oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat
      depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and
      pancreatic fat contents were similar in all groups and related with surrounding
      adipose masses or systemic insulin sensitivity. CONCLUSIONS: In ischemic CAD
      patients, glucose oxidation is enhanced and correlates inversely with insulin
      secretion. This can be seen as a mechanism to prevent glucose lowering because
      glucose is required in oxygen-deprived tissues. On the other hand, the
      accumulation of cardiac triglycerides may be a physiological adaptation to the
      limited fatty acid oxidative capacity. Our results underscore the urgent need of
      clinical trials that define the optimal/safest glycemic range in situations of
      myocardial ischemia.

PMID- 27045986
TI  - Stability of the Solid Electrolyte Interface on the Li Electrode in Li-S
      Batteries.
AB  - By means of high performance liquid chromatography-mass spectroscopy, the
      concentration of sulfur and polysulfides was determined in nonaqueous
      electrolytes. The stability of sulfur and Li in eight electrolytes was studied
      quantitatively. It was found that sulfur reacted with Li in most of the commonly
      used electrolytes for lithium-sulfur batteries. The reaction products between
      sulfur and Li were qualitatively identified. In some cases, the solid electrolyte
      interface on the Li can successfully prevent the interaction between S and Li;
      however, it was found that the solid electrolyte interface was damaged by
      polysulfide ions.

PMID- 27045987
TI  - Reduced Integrity of Right Lateralized White Matter in Patients with Primary
      Insomnia: A Diffusion-Tensor Imaging Study.
AB  - Purpose To analyze the integrity of white matter (WM) tracts in primary insomnia
      patients and provide better characterization of abnormal WM integrity and its
      relationship with disease duration and clinical features of primary insomnia.
      Materials and Methods This prospective study was approved by the ethics committee
      of the Guangdong No. 2 Provincial People's Hospital. Tract-based spatial
      statistics were used to compare changes in diffusion parameters of WM tracts from
      23 primary insomnia patients and 30 healthy control (HC) participants, and the
      accuracy of these changes in distinguishing insomnia patients from HC
      participants was evaluated. Voxel-wise statistics across subjects was performed
      by using a 5000-permutation set with family-wise error correction (family-wise
      error, P < .05). Multiple regressions were used to analyze the associations
      between the abnormal fractional anisotropy (FA) in WM with disease duration,
      Pittsburgh Sleep Quality Index, insomnia severity index, self-rating anxiety
      scale, and the self-rating depression scale in primary insomnia. Characteristics
      for abnormal WM were also investigated in tract-level analyses. Results Primary
      insomnia patients had lower FA values mainly in the right anterior limb of the
      internal capsule, right posterior limb of the internal capsule, right anterior
      corona radiata, right superior corona radiata, right superior longitudinal
      fasciculus, body of the corpus callosum, and right thalamus (P < .05, family-wise
      error correction). The receiver operating characteristic areas for the seven
      regions were acceptable (range, 0.60-0.74; 60%-74%). Multiple regression models
      showed abnormal FA values in the thalamus and body corpus callosum were
      associated with the disease duration, self-rating depression scale, and
      Pittsburgh Sleep Quality Index scores. Tract-level analysis suggested that the
      reduced FA values might be related to greater radial diffusivity. Conclusion This
      study showed that WM tracts related to regulation of sleep and wakefulness, and
      limbic cognitive and sensorimotor regions, are disrupted in the right brain in
      patients with primary insomnia. The reduced integrity of these WM tracts may be
      because of loss of myelination. ((c)) RSNA, 2016.

PMID- 27045988
TI  - Frequency and bandwidth conversion of single photons in a room-temperature
      diamond quantum memory.
AB  - The spectral manipulation of photons is essential for linking components in a
      quantum network. Large frequency shifts are needed for conversion between optical
      and telecommunication frequencies, while smaller shifts are useful for frequency
      multiplexing quantum systems, in the same way that wavelength division
      multiplexing is used in classical communications. Here we demonstrate frequency
      and bandwidth conversion of single photons in a room-temperature diamond quantum
      memory. Heralded 723.5 nm photons, with 4.1 nm bandwidth, are stored as optical
      phonons in the diamond via a Raman transition. Upon retrieval from the diamond
      memory, the spectral shape of the photons is determined by a tunable read pulse
      through the reverse Raman transition. We report central frequency tunability over
      4.2 times the input bandwidth, and bandwidth modulation between 0.5 and 1.9 times
      the input bandwidth. Our results demonstrate the potential for diamond, and Raman
      memories in general, as an integrated platform for photon storage and spectral
      conversion. 

PMID- 27045989
TI  - Solar cycles or random processes? Evaluating solar variability in Holocene
      climate records.
AB  - Many studies have reported evidence for solar-forcing of Holocene climate change
      across a range of archives. These studies have compared proxy-climate data with
      records of solar variability (e.g. (14)C or (10)Be), or have used time series
      analysis to test for the presence of solar-type cycles. This has led to some
      climate sceptics misrepresenting this literature to argue strongly that solar
      variability drove the rapid global temperature increase of the twentieth century.
      As proxy records underpin our understanding of the long-term processes governing
      climate, they need to be evaluated thoroughly. The peatland archive has become a
      prominent line of evidence for solar forcing of climate. Here we examine high
      resolution peatland proxy climate data to determine whether solar signals are
      present. We find a wide range of significant periodicities similar to those in
      records of solar variability: periods between 40-100 years, and 120-140 years are
      particularly common. However, periodicities similar to those in the data are
      commonly found in random-walk simulations. Our results demonstrate that solar
      type signals can be the product of random variations alone, and that a more
      critical approach is required for their robust interpretation. 

PMID- 27045990
TI  - Ruminants Contribute Fecal Contamination to the Urban Household Environment in
      Dhaka, Bangladesh.
AB  - In Dhaka, Bangladesh, the sensitivity and specificity of three human, three
      ruminant, and one avian source-associated QPCR microbial source tracking assays
      were evaluated using fecal samples collected on site. Ruminant-associated assays
      performed well, whereas the avian and human assays exhibited unacceptable cross
      reactions with feces from other hosts. Subsequently, child hand rinses (n = 44)
      and floor sponge samples (n = 44) from low-income-households in Dhaka were
      assayed for fecal indicator bacteria (enterococci, Bacteroidales, and Escherichia
      coli) and a ruminant-associated bacterial target (BacR). Mean enterococci
      concentrations were of 100 most probable number (MPN)/2 hands and 1000 MPN/225
      cm(2) floor. Mean concentrations of Bacteroidales were 10(6) copies/2 hands and
      10(5) copies/225 cm(2) floor. E. coli were detected in a quarter of hand rinse
      and floor samples. BacR was detected in 18% of hand rinse and 27% of floor
      samples. Results suggest that effective household fecal management should account
      not only for human sources of contamination but also for animal sources. The poor
      performance of the human-associated assays in the study area calls into the
      question the feasibility of developing a human-associated marker in urban slum
      environments, where domestic animals are exposed to human feces that have been
      disposed in pits and open drains.

PMID- 27045991
TI  - Economic Burden and Treatment Patterns of Cycling between Conventional Synthetic
      Disease-modifying Antirheumatic Drugs Among Biologic-treated Patients with
      Rheumatoid Arthritis.
AB  - PURPOSE: To assess the economic outcomes and treatment patterns among patients
      with rheumatoid arthritis (RA) who used 1, 2, or 3 or more conventional synthetic
      disease-modifying antirheumatic drugs (DMARDs) before receiving a biologic
      therapy. METHODS: Adult patients with >=2 RA diagnoses (International
      Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]
      codes 714.xx) on different dates, >=1 claim for a conventional synthetic DMARD,
      and >=1 claim for a biologic DMARD were identified from a large commercial claims
      database. The initiation date of the first biologic DMARD was defined as the
      index date. Based on the number of distinct conventional synthetic DMARDs
      initiated between the first RA diagnosis and the index date, patients were
      classified into 3 cohorts: those who used 1, 2, or 3 or more conventional
      synthetic DMARDs. Baseline characteristics were measured 6 months preindex date
      and compared between the 3 cohorts. All-cause health care costs (in 2014 US$)
      were compared during the follow-up period (12 months postbiologic initiation)
      using multivariable gamma models adjusting for baseline characteristics. Time to
      discontinuation of the index biologic DMARD and time to switching to a new DMARD
      were compared using multivariable Cox proportional hazards models. FINDINGS: The
      1, 2, and 3 or more conventional synthetic DMARD cohorts included 6215; 3227; and
      976 patients, respectively. At baseline, patients in the 3 or more conventional
      synthetic DMARD cohort had the least severe RA, as indicated by the lowest claims
      based index for RA severity score (1 vs 2 vs 3 or more = 6.1 vs 5.9 vs 5.8).
      During the study period, there was a significant association between number of
      conventional synthetic DMARDs and higher all-cause total health care costs
      (adjusted mean difference, 1 vs 2: $772; P < 0.001; 2 vs 3 or more: $2390; P <
      0.001). The all-cause medical and pharmacy costs were also significantly higher
      with the increasing number of conventional synthetic DMARDs. Patients who cycled
      more conventional synthetic DMARDs were also more likely to switch treatment
      after biologic initiation (1 vs 2: adjusted hazard ratio = 0.89; P = 0.005; 2 vs
      3 or more: adjusted hazard ratio = 0.89; P = 0.087). There were no differences in
      index biologic discontinuation between the 3 cohorts. IMPLICATIONS: Patients with
      RA who cycled more conventional synthetic DMARDs had increased economic burden in
      the 12 months following biologic initiation and were more likely to switch
      therapy. These results highlight the importance of timely switching to biologic
      DMARDs for the treatment of RA.

PMID- 27045992
TI  - Methods for Implementing and Reporting Patient-reported Outcome (PRO) Measures of
      Symptomatic Adverse Events in Cancer Clinical Trials.
AB  - PURPOSE: There is increasing interest to use patient-reported outcome (PRO)
      measures to evaluate symptomatic adverse events (AEs) in cancer treatment trials.
      However, there are currently no standard recommended approaches for integrating
      patient-reported AE measures into trials. METHODS: Approaches are identified from
      previous trials for selecting AEs for solicited patient reporting, administering
      patient-reported AE measures, and analyzing and reporting results. FINDINGS:
      Approaches for integrating patient-reported AE measures into cancer trials
      generally combine current standard methods for clinician-reported AEs and
      established best practices for using PRO measures. Specific AEs can be selected
      for a PRO questionnaire based on common and expected reactions in a given trial
      context, derived from literature review and qualitative/mixed-methods evaluations
      and should be the same set administered across all arms of a trial. A mechanism
      for collecting unsolicited patient-reported AEs will also ideally be included.
      Patients will preferably report at baseline and at the end of active treatment as
      well as on a frequent standardized schedule during active treatment, such as
      weekly from home, with a recall period corresponding to the frequency of
      reporting (eg, past 7 days). Less frequent reporting may be considered after an
      initial intensive monitoring period for trials of prolonged treatments and during
      long-term follow-up. Electronic PRO data collection is preferred. Backup data
      collection for missed PRO reports is advisable to boost response rates. Analysis
      can use a combination of approaches to AE and PRO data. If a high proportion of
      patients is experiencing baseline symptoms, systematic subtraction of these from
      on-study AEs should be considered to improve reporting of symptoms related to
      treatment. More granular longitudinal analyses of individual symptoms can also be
      useful. IMPLICATIONS: Methods are evolving for integrating patient-reported
      symptomatic AEs into cancer trials. These methods are expected to further evolve
      as more data from trials become available.

PMID- 27045994
TI  - Extraordinary Light-Induced Local Angular Momentum near Metallic Nanoparticles.
AB  - The intense local field induced near metallic nanostructures provides strong
      enhancements for surface-enhanced spectroscopies, a major focus of plasmonics
      research over the past decade. Here we consider that plasmonic nanoparticles can
      also induce remarkably large electromagnetic field gradients near their surfaces.
      Sizeable field gradients can excite dipole-forbidden transitions in nearby atoms
      or molecules and provide unique spectroscopic fingerprinting for chemical and
      bimolecular sensing. Specifically, we investigate how the local field gradients
      near metallic nanostructures depend on geometry, polarization, and wavelength. We
      introduce the concept of the local angular momentum (LAM) vector as a useful
      figure of merit for the design of nanostructures that provide large field
      gradients. This quantity, based on integrated fields rather than field gradients,
      is particularly well-suited for optimization using numerical grid-based full wave
      electromagnetic simulations. The LAM vector has a more compact structure than the
      gradient matrix and can be straightforwardly associated with the angular momentum
      of the electromagnetic field incident on the plasmonic structures.

PMID- 27045993
TI  - Advances in Hereditary Colorectal and Pancreatic Cancers.
AB  - PURPOSE: Innovations in genetic medicine have led to improvements in the early
      detection, prevention, and treatment of cancer for patients with inherited risks
      of gastrointestinal cancer, particularly hereditary colorectal cancer and
      hereditary pancreatic cancer. METHODS: This review provides an update on recent
      data and key advances that have improved the identification, understanding, and
      management of patients with hereditary colorectal cancer and hereditary
      pancreatic cancer. FINDINGS: This review details recent and emerging data that
      highlight the developing landscape of genetics in hereditary colorectal and
      pancreatic cancer risk. A summary is provided of the current state-of-the-art
      practices for identifying, evaluating, and managing patients with suspected
      hereditary colorectal cancer and pancreatic cancer risk. The impact of next
      generation sequencing technologies in the clinical diagnosis of hereditary
      gastrointestinal cancer and also in discovery efforts of new genes linked to
      familial cancer risk are discussed. Emerging targeted therapies that may play a
      particularly important role in the treatment of patients with hereditary forms of
      colorectal cancer and pancreatic cancer are also reviewed. Current approaches for
      pancreatic cancer screening and the psychosocial impact of such procedures are
      also detailed. IMPLICATIONS: Given the availability of new diagnostic, risk
      reducing, and therapeutic strategies that exist for patients with hereditary risk
      of colorectal or pancreatic cancer, it is imperative that clinicians be vigilant
      about evaluating patients for hereditary cancer syndromes. Continuing to advance
      genetics research in hereditary gastrointestinal cancers will allow for more
      progress to be made in personalized medicine and prevention.

PMID- 27045995
TI  - Cationic Pd(II) complexes acting as topoisomerase II inhibitors: Synthesis,
      characterization, DNA interaction and cytotoxicity.

PMID- 27045996
TI  - Relations between symptom severity, illness perceptions, visceral sensitivity,
      coping strategies and well-being in irritable bowel syndrome guided by the common
      sense model of illness.
AB  - Irritable Bowel Syndrome (IBS) is a common condition affecting around 10-20% of
      the population and associated with poorer psychological well-being and quality of
      life. The aim of the current study was to explore the efficacy of the Common
      Sense Model (CSM) using Structural Equation Modelling (SEM) in an IBS cohort. One
      hundred and thirty-one IBS patients (29 males, 102 females, mean age 38 years)
      participating in the IBSclinic.org.au pre-intervention assessment were included.
      Measures included IBS severity (Irritable Bowel Syndrome Severity Scoring
      System), coping patterns (Carver Brief COPE), visceral sensitivity (Visceral
      Sensitivity Index), illness perceptions (Brief Illness Perceptions
      Questionnaire), psychological distress (Depression, Anxiety and Stress Scale),
      and quality of life (IBS Quality of Life scale; IBS-QoL). Using SEM, a final
      model with an excellent fit was identified (chi2 (8) = 11.91, p = .16, chi2/N =
      1.49, CFI > .98, TLI > .96, SRMR < .05). Consistent with the CSM, Illness
      perceptions were significantly and directly influenced by IBS severity (beta =
      .90, p < .001). Illness perceptions in turn directly influenced maladaptive
      coping (beta = .40, p < .001) and visceral sensitivity (beta = .70, p < .001).
      Maladaptive coping and visceral sensitivity were significantly associated with
      psychological distress (beta = .55, p < .001; beta = .22, p < .01) and IBS-QoL
      (beta = -.28, p < .001; beta = -.62, p < .001). Based on these findings, we argue
      that to augment the adverse impact of IBS severity on IBS-QoL and psychological
      distress, psychological interventions will be best to target the mediating
      psychological processes including illness beliefs, visceral sensitivity and
      maladaptive coping.

PMID- 27045998
TI  - Synthesis of cholic-acid-carrying polymer and in-vitro evaluation of hepatoma
      targeting nanoparticles decorated with the polymer.
AB  - The specific interaction between bile acids and the bile acids transporters
      provides a promising way for hepatoma-targeted drug delivery. We synthesized an
      amphipathic polymer containing cholic acid (CA), the main bile acids in body, and
      prepared CA-functionalized nanoparticles to target hepatoma cells. Poly-[3-(4
      vinylbenzonate)-7, 12-dihydroxy-5-cholan-24-oic acid] (PVBCA) was synthesized by
      introducing methyl cholate onto polyvinyl benzoate polymer backbone, and was
      characterized by (1)H-NMR, FT-IR, and GFC. PVBCA can be incorporated onto PLGA
      nanoparticles surface via the emulsion-solvent evaporation procedure, resulting
      in the nanoparticles carrying CA moieties on their surface. The binding of CA
      moieties to the bile acids' transporters on the cell membrane enhances the
      cellular uptake of the nanoparticles significantly. The SMMC-7721 cell uptake of
      PVBCA-decorated nanoparticles increases with amount of incorporated PVBCA and is
      2- to 2.8-fold higher than that of the normal PLGA nanoparticles. By exclusion of
      specific endocytosis pathways using chemical inhibitors, we found that the uptake
      mechanism of PVBCA-decorated nanoparticles was mainly attributed to clathrin-and
      caveolae-independent endocytosis, which was distinct from that of PLGA
      nanoparticles. The present study provides a simple and versatile method for
      hepatoma-targeted delivery of nanoparticles.

PMID- 27045997
TI  - N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone
      acetylation in brown adipocytes.
AB  - Histone acetylation depends on the abundance of nucleo-cytoplasmic acetyl-CoA.
      Here, we present a novel route for cytoplasmic acetyl-CoA production in brown
      adipocytes. N-acetylaspartate (NAA) is a highly abundant brain metabolite
      catabolized by aspartoacylase yielding aspartate and acetate. The latter can be
      further used for acetyl-CoA production. Prior to this work, the presence of NAA
      has not been described in adipocytes. Here, we show that accumulation of NAA
      decreases the brown adipocyte phenotype. We increased intracellular NAA
      concentrations in brown adipocytes via media supplementation or knock-down of
      aspartoacylase and measured reduced lipolysis, thermogenic gene expression, and
      oxygen consumption. Combinations of approaches to increase intracellular NAA
      levels showed additive effects on lipolysis and gene repression, nearly
      abolishing the expression of Ucp1, Cidea, Prdm16, and Ppara. Transcriptome
      analyses of aspartoacylase knock-down cells indicate deficiencies in acetyl-CoA
      and lipid metabolism. Concordantly, cytoplasmic acetyl-CoA levels and global
      histone H3 acetylation were decreased. Further, activating histone marks (H3K27ac
      and H3K9ac) in promoters/enhancers of brown marker genes showed reduced
      acetylation status. Taken together, we present a novel route for cytoplasmic
      acetyl-CoA production in brown adipocytes. Thereby, we mechanistically connect
      the NAA pathway to the epigenomic regulation of gene expression, modulating the
      phenotype of brown adipocytes. 

PMID- 27046000
TI  - Correction to Determination of DNA and RNA Methylation in Circulating Tumor Cells
      by Mass Spectrometry.

PMID- 27045999
TI  - Black African and Caribbean British Communities' Perceptions of Memory Problems:
      "We Don't Do Dementia.".
AB  - OBJECTIVES: We aimed to identify and explore the barriers to help-seeking for
      memory problems, specifically within UK Black African and Caribbean communities.
      METHOD: We purposively recruited participants from community groups and
      subsequent snowball sampling, to achieve a maximum variation sample and employed
      thematic analysis. Our qualitative semi-structured interviews used a vignette
      portraying a person with symptoms of dementia, and we asked what they or their
      family should do. We stopped recruiting when no new themes were arising. RESULTS
      AND SIGNIFICANCE: We recruited 50 people from a range of age groups, country of
      origin, time in the UK, religion and socio-economic background. Some of the
      barriers to presentation with dementia have been reported before, but others were
      specific to this group and newly identified. Many people recognised forgetfulness
      but neither that it could be indicative of dementia, nor the concept of dementia
      as applying to them. Dementia was viewed as a white person's illness.
      Participants felt there was little point in consulting a doctor for
      forgetfulness. Many thought that seeing a GP was only for severe problems. Some
      said that their culture was secretive and highly valued privacy of personal
      affairs and therefore did not want to discuss what they regarded as a private and
      stigmatising problem with a GP. Participants did not appreciate their GP could
      refer to memory services who have more time and expertise. They were concerned
      about harm from medication and compulsory institutionalisation. Care should be
      from the family. Any intervention should emphasise the legitimacy of seeing a
      doctor early for memory concerns, that dementia is a physical illness which also
      occurs in the Black community, that help and time are available from memory
      services whose role is to prolong independence and support families in caring.

PMID- 27046001
TI  - Choroidal metastasis as a presenting manifestation of a lung adenocarcinoma with
      response to afatinib.
AB  - CASE REPORT: We present the case of a 55-year-old man with a non-small cell lung
      adenocarcinoma, who presented with choroidal metastasis. The patient showed a
      decrease in visual acuity. His evaluation revealed unilateral choroidal
      metastasis secondary to carcinoma of the lung. The patient received afatinib with
      complete regression of choroidal metastasis after one year follow-up. DISCUSSION:
      Choroidal metastasis may be the initial sign of lung cancer. This case highlights
      the importance of a thorough systemic evaluation in patients with choroidal
      tumours. Afatinib was effective against choroidal metastasis of a lung
      adenocarcinoma with EFGR mutation.

PMID- 27046002
TI  - Model based adaptive control of a continuous capture process for monoclonal
      antibodies production.
AB  - A two-column capture process for continuous processing of cell-culture
      supernatant is presented. Similar to other multicolumn processes, this process
      uses sequential countercurrent loading of the target compound in order maximize
      resin utilization and productivity for a given product yield. The process was
      designed using a novel mechanistic model for affinity capture, which takes both
      specific adsorption as well as transport through the resin beads into account.
      Simulations as well as experimental results for the capture of an IgG antibody
      are discussed. The model was able to predict the process performance in terms of
      yield, productivity and capacity utilization. Compared to continuous capture with
      two columns operated batch wise in parallel, a 2.5-fold higher capacity
      utilization was obtained for the same productivity and yield. This results in an
      equal improvement in product concentration and reduction of buffer consumption.
      The developed model was used not only for the process design and optimization but
      also for its online control. In particular, the unit operating conditions are
      changed in order to maintain high product yield while optimizing the process
      performance in terms of capacity utilization and buffer consumption also in the
      presence of changing upstream conditions and resin aging. 

PMID- 27046003
TI  - Instrument modifications that produced reduced plate heights <2 with sub-2 MUm
      particles and 95% of theoretical efficiency at k=2 in supercritical fluid
      chromatography.
AB  - The concept of peak fidelity was shown to be helpful in modeling tubing and
      detector cell dimensions. Connection tubing and flow cell variances were modeled
      to determine appropriate internal ID's, lengths, and volumes. A low dispersion
      plumbing configuration, based on these calculations, was assembled to replace the
      standard plumbing and produced the reported results. The modifications made were
      straightforward using commercially available parts. The full theoretical
      efficiency of a 3*100 mm column packed with 1.8 MUm totally porous particles was
      achieved for the first time in supercritical fluid chromatography (SFC). Peak
      fidelity of >0.95 was maintained to below k=2. A reduced plate height as low as
      1.87 was measured. Thus, true "ultra high performance" SFC was achieved, with the
      results a major improvement from all previous SFC reports. Since there were no
      efficiency losses, none could be attributed to thermal gradients caused by the
      expansion of the fluid over large pressure drops, under the conditions used.
      Similarly, changes in diffusion coefficients caused by significant decreases in
      density during expansion are apparently balanced by the increase in linear
      velocity, keeping the ratio between the diffusion coefficient and the linear
      velocity a constant. Changing modifier concentration to change retention was
      shown to not be a significant problem. All these issues have been a concern in
      the past. Diffusion coefficients, and viscosity data needs to be collected at
      high pressures before the actual limits of SFC can be discovered.

PMID- 27046004
TI  - Bromate peak distortion in ion chromatography in samples containing high chloride
      concentrations.
AB  - In this study, the effect of column overload of the matrix ion, chloride, on the
      elution peak profiles of trace bromate is investigated. The resultant peak
      profiles of chloride and bromate are explained on the basis of competitive
      Langmuir isotherms. The Thermo IonPac AS9-HC, AS19 and AS23 columns are
      recommended by the manufacturer for bromate (a carcinogen) analysis. Under trace
      conditions, these columns provide baseline resolution of bromate from matrix ions
      such as chloride (Rs=2.9, 3.3 and 3.2, respectively for the three columns).
      Injection of 10-300 mM chloride with both hydroxide and carbonate eluents
      resulted in overload on these columns. On the basis of competitive Langmuir
      isotherms, a deficiency in the local concentration of the more retained eluent in
      addition to analyte overload leads to fronting of the overloaded analyte peak.
      The peak asymmetries (B/A10%) for chloride changed from 1.0 (Gaussian) under
      trace conditions to 0.7 (fronting) at 300 mM Cl(-) for IonPac AS9-HC, 0.9-0.6 for
      AS19 and 0.8-0.5, for AS23, respectively. The 10mM bromate peak is initially near
      Gaussian (B/A10%=0.9) but becomes increasingly distorted and pulled back into the
      chloride peak as the concentration of chloride increased. Increasing the eluent
      strength reduced the pull-back effect on bromate and fronting in chloride in all
      cases.

PMID- 27046005
TI  - A Family of Photolabile Nitroveratryl-Based Surfactants That Self-Assemble into
      Photodegradable Supramolecular Structures.
AB  - Here we report the synthesis and characterization of a family of photolabile
      nitroveratryl-based surfactants that form different types of supramolecular
      structures depending on the alkyl chain lengths ranging from 8 to 12 carbon
      atoms. By incorporating a photocleavable alpha-methyl-o-nitroveratryl moiety, the
      surfactants can be degraded, along with their corresponding supramolecular
      structures, by light irradiation in a controlled manner. The self-assembly of the
      amphiphilic surfactants was characterized by conductometry to determine the
      critical concentration for the formation of the supramolecular structures,
      transmission electron microscopy to determine the size and shape of the
      supramolecular structures, and dynamic light scattering (DLS) to determine the
      hydrodynamic diameter of the structures in aqueous solutions. The
      photodegradation of the surfactants and the supramolecular structures was
      confirmed using UV-vis spectroscopy, mass spectrometry, and DLS. This surfactant
      family could be potentially useful in drug delivery, organic synthesis, and other
      applications.

PMID- 27046006
TI  - Noncompliance with guidelines on proton pump inhibitor prescription as
      gastroprotection in hospitalized surgical patients who are prescribed NSAIDs.
AB  - BACKGROUND AND AIMS: As NSAIDs can cause serious upper gastrointestinal harm,
      guidelines have been established for the prescribing of proton pump inhibitors
      (PPIs) in high-risk patients using NSAIDs. Studies examining guideline compliance
      in surgical patients are scarce. Therefore, a retrospective cross-sectional
      database study was carried out aimed at determining the proportion of
      noncompliance with the Dutch guideline and determining the association of several
      factors with this noncompliance. MATERIALS AND METHODS: Hospital admissions of
      patients on surgical wards of Erasmus University Medical Center between 1 January
      2013 and 1 August 2014 were included in which an NSAID was newly prescribed.
      Preadmission PPI use was excluded. The main outcome was the proportion of
      noncompliance with the guideline. As a secondary outcome, the association of
      several potential risk factors with noncompliance was assessed. The proportion of
      guideline noncompliance was calculated as the percentage of all included surgical
      ward admissions. For the secondary analysis, univariate and multivariable
      logistic regression analyses were carried out. RESULTS: A total of 409 admissions
      were included. The proportion of admissions in which guideline noncompliance was
      present was 46.6%, mostly because of incorrectly added PPIs. Coxib use [adjusted
      odds ratio 0.22 (95% confidence interval 0.12-0.44)], polypharmacy (the use of
      five or more drugs) [2.18 (1.27-3.76)], and the surgical wards orthopedics [22.32
      (5.38-92.55)], plastic surgery [10.82 (2.51-46.59)], trauma surgery [5.78 (1.47
      22.70)], and transplant/vascular surgery [4.45 (1.10-18.00)] were statistically
      significantly associated with noncompliance. CONCLUSION: Noncompliance with the
      guideline on NSAID use and gastroprotection is present in almost half of surgical
      hospital admissions and mainly involves overprescribing.

PMID- 27046009
TI  - Self-Rated Depression Severity Relative to Clinician-Rated Depression Severity:
      Trait Stability and Potential Role in Familial Transmission of Suicidal Behavior.
AB  - Self-rated depression and hopelessness severity are predictors of suicide attempt
      in major depression. This study evaluated whether: (1) greater self-rated
      distress relative to severity of clinician-rated depression is a trait; (2) that
      trait is familial; and (3) that trait is linked to familial transmission of
      suicidal behavior. A total of 285 mood disorder probands and 457 offspring were
      assessed twice, at least 1 year apart. Family and subject intra-class
      correlations for self-report depression and hopelessness, controlling for
      clinician-rated depression severity, were computed. Mixed general linear models
      determined offspring-proband correlations. Within-individual intra-class
      correlation (ICC) for depression-hopelessness was 37.8% (bootstrap 95% CI: 31.0
      46.3%). Parent-offspring ICC was 10.7% (bootstrap 95% CI: 3.5-17.8%). Suicide
      attempt concordant parent-offspring correlation for subjective depression was
      positive, but negative for attempter parent and nonattempter offspring (p = .0213
      for slope interaction). Pessimism was greater in proband or offspring attempters
      than proband or offspring nonattempters (p < .05). Self-reported hopelessness is
      partly trait-dependent, and there is modest familial transmission of self
      reported depression linked to suicidal behavior that may partly explain familial
      transmission of suicidal behavior.

PMID- 27046011
TI  - High-quality dialysis: a lesson from the Japanese experience: Effects of membrane
      material on nutritional status and dialysis-related symptoms.
AB  - High-quality dialysis does not always mean high efficiency; dialysis should
      maintain nutritional balance and full biocompatibility. In undergoing treatment
      with polymethylmethacrylate (PMMA) and/or ethylene vinyl alcohol copolymer (EVAL)
      membrane dialysers, the body weight decrease caused by polysulfone membrane has
      been dramatically improved for those receiving predilution online
      haemodiafiltration (HDF) as well. These membranes are assumed to somewhat
      suppress the clearance of small molecular weight substances to maintain an
      exquisite balance of broadly removing low molecular weight proteins. This removal
      process is assumed to be extremely close to the balance maintained by the
      clearing characteristics of the kidneys. On the other hand, fluid purification is
      also one of the important factors in high-quality dialysis. Bacteriological
      contamination of dialysis fluid is one of the serious factors that deteriorate
      the biocompatibility of dialysis therapy. From this therapeutic concept, the
      patient survival rate is excellent in our facilities: the 1-year survival rate is
      91.1% and the 5-year survival rate is 76.6%, although the mean age of our
      patients is 69 years. We usually adjust the therapeutic modality based on patient
      complaints, and we call this concept 'patient-oriented dialysis' (POD). In the
      POD system, the prevalence of uraemic pruritus or sleep disturbances was lower
      than that of the DOPPS. The protein-leaking dialysis modalities with PMMA, EVAL
      or predilution online HDF form the key concept in the POD system.

PMID- 27046010
TI  - Phenomenological and microscopic theories for catch bonds.
AB  - Lifetimes of bound states of protein complexes or biomolecule folded states
      typically decrease when subject to mechanical force. However, a plethora of
      biological systems exhibit the counter-intuitive phenomenon of catch bonding,
      where non-covalent bonds become stronger under externally applied forces. The
      quest to understand the origin of catch-bond behavior has led to the development
      of phenomenological and microscopic theories that can quantitatively recapitulate
      experimental data. Here, we assess the successes and limitations of such theories
      in explaining experimental data. The most widely applied approach is a
      phenomenological two-state model, which fits all of the available data on a
      variety of complexes: actomyosin, kinetochore-microtubule, selectin-ligand, and
      cadherin-catenin binding to filamentous actin. With a primary focus on the
      selectin family of cell-adhesion complexes, we discuss the positives and
      negatives of phenomenological models and the importance of evaluating the
      physical relevance of fitting parameters. We describe a microscopic theory for
      selectins, which provides a structural basis for catch bonds and predicts a
      crucial allosteric role for residues Asn82-Glu88. We emphasize the need for new
      theories and simulations that can mimic experimental conditions, given the
      complex response of cell adhesion complexes to force and their potential role in
      a variety of biological contexts.

PMID- 27046012
TI  - Dirty limit scattering behind the decreased anisotropy of doped YBa2Cu3O7-delta
      thin films.
AB  - We measured the resistivity of pulsed-laser-deposited BaCeO3 (BCO)-doped YBCO
      thin films containing spherical BCO particles in fields up to 30 T. The average
      diameter of the particles depends on the dopant concentration being below 4 nm in
      all the samples. Raised values of the upper critical field, Bc2, were observed in
      all the samples. Additionally, the parameter gamma, describing the electron mass
      anisotropy, decreased from 6.2 in the undoped sample to 3.1 in the 8 wt.% BCO
      doped sample. These results can be explained by the increased number of defects
      decreasing the mean free path of electrons and thus lowering the coherence
      length, which in turn increases Bc2.

PMID- 27046013
TI  - Diffusion Tensor Imaging Correlates with Short-Term Myelopathy Outcome in
      Patients with Cervical Spondylotic Myelopathy.
AB  - OBJECTIVE: To determine if spinal cord diffusion tensor imaging indexes correlate
      with short-term clinical outcome in patients undergoing elective cervical spine
      surgery for cervical spondylotic myelopathy (CSM). METHODS: A prospective
      consecutive cohort study was performed in patients undergoing elective cervical
      spine surgery for CSM. After obtaining informed consent, patients with CSM
      underwent preoperative T2-weighted magnetic resonance imaging and diffusion
      tensor imaging of the cervical spine. Fractional anisotropy (FA) values at the
      level of maximum cord compression and at the noncompressed C1-2 level were
      calculated on axial images. We recorded the modified Japanese Orthopaedic
      Association (mJOA) scale, Neck Disability Index, and Short Form-36 physical
      functioning subscale scores for all patients preoperatively and 3 months
      postoperatively. Statistical analysis was performed to identify correlations
      between FA and clinical outcome scores. RESULTS: The study included 27 patients
      (mean age 54.5 years +/- 1.9, 12 men). The mean postoperative changes in mJOA
      scale, Neck Disability Index, and Short Form-36 physical functioning subscale
      scores were 0.9 +/- 0.3, -6.0 +/- 1.9, and 3.4 +/- 1.9. The mean FA at the level
      of maximum compression was significantly lower than the mean FA at the C1-2 level
      (0.5 vs. 0.55, P = 0.01). FA was significantly correlated with change in mJOA
      scale score (Pearson r = -0.42, P = 0.02). FA was significantly correlated with
      the preoperative mJOA scale score (Pearson r = 0.65, P < 0.001). CONCLUSIONS:
      Preoperative FA at the level of maximum cord compression significantly correlates
      with the 3-month change in mJOA scale score among patients with CSM. FA was also
      significantly associated with preoperative mJOA scale score and is a potential
      biomarker for spinal cord dysfunction in CSM.

PMID- 27046014
TI  - Cranial Center of Mass Compared to C7 Plumb Line Alignment in Adult Spinal
      Deformity.
AB  - OBJECTIVE: To report the cranial center of mass (CCOM) progression in surgically
      treated patients for adult spinal deformity (ASD). The C7 plumb line/sagittal
      vertical axis (SVA) has important relationships with patient-reported outcomes;
      however, this has not yet been defined for CCOM. METHODS: Patients with
      consecutive ASD who were undergoing surgery greater than 5 levels of fusion
      between 2007 and 2012 and had radiographic, clinical, and outcomes data spanning
      >=2 years were analyzed, retrospectively. Radiographic parameters were obtained
      preoperatively and at 6 weeks, 1 year, and 2 years postoperatively. Statistical
      analysis included descriptives (measures of central tendency, dispersion,
      frequencies), independent Student t tests, chi(2) square, Pearson correlation,
      and Kaplan-Meyer curve. RESULTS: Fifty-eight patients (10 male, 48 female) with a
      mean age of 60.5 years (range, 27-81 years) were reviewed. The mean preoperative
      SVA was 7.40 cm (SD = 5.51; 37/58 [63.8%] malalignment), and mean CCOM was 10.0
      cm (SD = 6.58; 47/58 [81%] malalignment). Six-week postoperative SVA and CCOM was
      -0.17 cm (SD = 3.3) and 2.5 cm (SD = 4.11), respectively. SVA malalignment was
      12.7% and CCOM malalignment was 38.2% at 6 weeks postop. Six week (absolute), 6
      week change, and patient number at 6 weeks who were CCOM malaligned was
      significant compared with SVA (P = 0.003, P < 0.001, P < 0.001, respectively).
      SRS appearance worsened as preoperative SVA and CCOM increased (P < 0.05), and 2
      year SRS appearance and mental health was worsened as 2-year SVA and CCOM
      increased (P < 0.05). SVA malalignment was 8 and 10 at 1 and 2 years,
      respectively, and CCOM malalignment was 24 and 32, respectively. Kaplan-Meier
      curve demonstrates persistent malalignment of CCOM at 6 weeks if not corrected.
      CONCLUSION: CCOM alignment restoration is an important parameter in ASD, and
      malalignment is consistent over time.

PMID- 27046015
TI  - Prediction of High-Grade Pediatric Meningiomas: Magnetic Resonance Imaging
      Features Based on T1-Weighted, T2-Weighted, and Contrast-Enhanced T1-Weighted
      Images.
AB  - BACKGROUND: Prediction of high-grade meningiomas before surgery is essential to
      determine optimal treatment strategies; however, the relationship between
      radiologic features and malignancy of meningiomas in pediatric patients has not
      been clearly demonstrated. The aim of this study was to identify preoperative
      magnetic resonance imaging features that are significantly correlated with high
      risk of high-grade pediatric meningiomas. METHODS: We retrospectively reviewed
      preoperative magnetic resonance imaging features and histopathologic diagnosis
      according to the 2007 World Health Organization classification system for
      intracranial tumors of 79 pediatric meningiomas from 2005 to 2015. World Health
      Organization grade II and III meningiomas were defined as high-grade meningiomas.
      The relationship between the radiologic findings and incidence of high-grade
      meningiomas was assessed initially with univariate analysis and then corrected by
      multivariate analysis. RESULTS: According to univariate analysis, heterogeneous
      tumor enhancement, an unclear tumor-brain interface, tumor cyst, type of dural
      attachment, lateral location, positive capsular enhancement, and irregular shape
      of tumor were strong predictive factors for high-grade meningiomas. When
      corrected by multivariate analysis, an unclear tumor-brain interface (P < 0.001;
      odds ratio = 10.4; 95% confidence interval, 3.0-37.0), lateral location (P =
      0.014; odds ratio = 4.9; 95% confidence interval, 1.4-17.6), and narrow base (P =
      0.001; odds ratio = 8.3; 95% confidence interval, 2.5-27.1) were strong
      independent predictive factors for high-grade meningiomas. CONCLUSIONS: In
      pediatric patients, meningiomas with an unclear tumor-brain interface, lateral
      location, and narrow base on preoperative magnetic resonance imaging are more
      likely to be high-grade meningiomas. Our results may be helpful in decision
      making regarding therapeutic strategies for pediatric patients with meningiomas.

PMID- 27046016
TI  - Acute Progression of Recurrent Meningioma during Luteinizing Hormone-Releasing
      Hormone Agonist Treatment for Prostate Cancer.
AB  - BACKGROUND: Meningiomas are the most common type of benign brain tumor, and the
      incidence of meningioma in women is more than twofold higher than in men. Several
      studies have demonstrated that hormones are somehow related to the growth of
      meningiomas. CASE DESCRIPTION: A 72-year-old man with benign meningioma underwent
      tumor resection and had no recurrence for 18 years. He was found to have prostate
      cancer, and he received hormonal therapy with a luteinizing hormone-releasing
      hormone (LHRH) agonist. Two years later, he developed severe cognitive
      dysfunction and gait disturbance. Gadolinium-enhanced brain magnetic resonance
      imaging revealed a large recurrent mass and obstructive hydrocephalus. Staged
      resection was performed and stereotactic radiation therapy was administered
      against the residual tumor. His symptoms improved after endoscopic third
      ventriculostomy for obstructive hydrocephalus and his residual tumor remains
      stable. CONCLUSIONS: This is the first report of a case in which an LHRH agonist
      promoted the growth of a pre-existing meningioma. We suggest that patients with a
      history of meningioma who are receiving LHRH agonist treatment should be closely
      monitored.

PMID- 27046017
TI  - Controlled single-cell deposition and patterning by highly flexible hollow
      cantilevers.
AB  - Single-cell patterning represents a key approach to decouple and better
      understand the role and mechanisms of individual cells of a given population. In
      particular, the bottom-up approach of engineering neuronal circuits with a
      controlled topology holds immense promises to perceive the relationships between
      connectivity and function. In order to accommodate these efforts, highly flexible
      SU-8 cantilevers with integrated microchannels have been fabricated for both
      additive and subtractive patterning. By directly squeezing out single cells onto
      adhesive surfaces, controlled deposition with a spatial accuracy of 5 MUm could
      be achieved, while subtractive patterning has been realized by selective removal
      of targeted single cells. Complex cell patterns were created on substrates pre
      patterned with cell-adhesive and repulsive areas, preserving the original pattern
      geometry for long-term studies. For example, a circular loop with a diameter of
      530 MUm has been realized using primary hippocampal neurons, which were fully
      connected to their respective neighbors along the loop. Using the same
      cantilevers, the versatility of the technique has also been demonstrated via in
      situ modification of already mature neuronal cultures by both detaching
      individual cells of the population and adding fresh ones, incorporating them into
      the culture.

PMID- 27046018
TI  - Quantum Monte Carlo Study of the Reactions of CH with Acrolein: Major and Minor
      Channels.
AB  - Acrolein is an important unsaturated hydrocarbon, containing both C?O and C?C
      bonds, and responsible for atmospheric pollution. A recent study of major
      reactions of CH with acrolein has been supplemented with computations of other
      reactions of the system. Similar to the previous approach, the quantum Monte
      Carlo (QMC) method in the accurate diffusion Monte Carlo (DMC) method was
      implemented. Single determinant wave functions were used as trial functions for
      the random walks. Rate coefficients and product branching ratios were computed by
      solving master equations using the MultiWell software suite. At room temperature,
      the dominant product channels are 2-methylvinyl + CO (P6), 1,3-butadienal + H
      (P2), and furan + H (P1). At elevated temperatures, 2,3-butadienal + H (P10) is
      also a major product. The chain decomposition pathway to form C3H4 + HCO was not
      competitive with the cyclization pathway at any of the temperatures studied. The
      DMC branching fractions of the products formed in the subject reaction are in
      reasonable accord with previous experimental and theoretical values. The computed
      rate coefficients were found to be independent of pressure at temperatures
      relevant to combustion (1500-2500 K). 

PMID- 27046019
TI  - Catalytic, Diastereoselective 1,2-Difluorination of Alkenes.
AB  - We describe a direct, catalytic approach to the 1,2-difluorination of alkenes.
      The method utilizes a nucleophilic fluoride source and an oxidant in conjunction
      with an aryl iodide catalyst and is applicable to alkenes with all types of
      substitution patterns. In general, the vicinal difluoride products are produced
      with high diastereoselectivities. The observed sense of stereoinduction
      implicates anchimeric assistance pathways in reactions of alkenes bearing
      neighboring Lewis basic functionality. 

PMID- 27046020
TI  - Design, Synthesis, Acaricidal/Insecticidal Activity, and Structure-Activity
      Relationship Studies of Novel Oxazolines Containing Sulfone/Sulfoxide Groups
      Based on the Sulfonylurea Receptor Protein-Binding Site.
AB  - Enormous compounds containing sulfone/sulfoxide groups have been used in a
      variety of fields, especially in drug and pesticide design. To search for novel
      environmentally benign and ecologically safe pesticides with unique modes of
      action, a series of 2,4-diphenyl-1,3-oxazolines containing sulfone/sulfoxide
      groups as chitin synthesis inhibitors (CSIs) were designed and synthesized on the
      basis of the sulfonylurea receptor protein-binding site for CSIs. Their
      structures were characterized by (1)H and (13)C nuclear magnetic resonance and
      high-resolution mass spectrometry. The acaricidal and insecticidal activities of
      the new compounds were evaluated. It was found that most of the target compounds
      displayed wonderful acaricidal activities against spider mite (Tetranychus
      cinnabarinus) larvae and eggs. Especially compounds I-4, II-3, and II-4 displayed
      higher activities than commercial etoxazole at a concentration of 2.5 mg L(-1).
      Some target compounds exhibited insecticidal activities against lepidopteran
      pests. The present work demonstrated that these compounds containing
      sulfone/sulfoxide groups could be considered as potential candidates for the
      development of novel acaricides in the future. 

PMID- 27046021
TI  - Fat composition of vegetable oil spreads and margarines in the USA in 2013: a
      national marketplace analysis.
AB  - Worldwide, the fat composition of spreads and margarines ("spreads") has
      significantly changed over the past decades. Data on fat composition of US
      spreads are limited and outdated. This paper compares the fat composition of
      spreads sold in 2013 to that sold in 2002 in the USA. The fat composition of 37
      spreads representing >80% of the US market sales volume was determined by
      standard analytical methods. Sales volume weighted averages were calculated. In
      2013, a 14 g serving of spread contained on average 7.1 g fat and 0.2 g trans
      fatty acids and provided 22% and 15% of the daily amounts recommended for male
      adults in North America of omega-3 alpha-linolenic acid and omega-6 linoleic
      acid, respectively. Our analysis of the ingredient list on the food label showed
      that 86% of spreads did not contain partially hydrogenated vegetable oils (PHVO)
      in 2013. From 2002 to 2013, based on a 14 g serving, total fat and trans-fatty
      acid content of spreads decreased on average by 2.2 g and 1.5 g, respectively. In
      the same period, the overall fat composition improved as reflected by a decrease
      of solid fat (from 39% to 30% of total-fatty acids), and an increase of
      unsaturated fat (from 61% to 70% of total-fatty acids). The majority of US
      spreads no longer contains PHVO and can contribute to meeting dietary
      recommendations by providing unsaturated fat. 

PMID- 27046022
TI  - Does Sleep Improve Your Grammar? Preferential Consolidation of Arbitrary
      Components of New Linguistic Knowledge.
AB  - We examined the role of sleep-related memory consolidation processes in learning
      new form-meaning mappings. Specifically, we examined a Complementary Learning
      Systems account, which implies that sleep-related consolidation should be more
      beneficial for new hippocampally dependent arbitrary mappings (e.g. new
      vocabulary items) relative to new systematic mappings (e.g. grammatical
      regularities), which can be better encoded neocortically. The hypothesis was
      tested using a novel language with an artificial grammatical gender system. Stem
      referent mappings implemented arbitrary aspects of the new language, and
      determiner/suffix+natural gender mappings implemented systematic aspects (e.g.
      tib scoiffesh + ballerina, tib mofeem + bride; ked jorool + cowboy, ked heefaff +
      priest). Importantly, the determiner-gender and the suffix-gender mappings varied
      in complexity and salience, thus providing a range of opportunities to detect
      beneficial effects of sleep for this type of mapping. Participants were trained
      on the new language using a word-picture matching task, and were tested after a 2
      hour delay which included sleep or wakefulness. Participants in the sleep group
      outperformed participants in the wake group on tests assessing memory for the
      arbitrary aspects of the new mappings (individual vocabulary items), whereas we
      saw no evidence of a sleep benefit in any of the tests assessing memory for the
      systematic aspects of the new mappings: Participants in both groups extracted the
      salient determiner-natural gender mapping, but not the more complex suffix
      natural gender mapping. The data support the predictions of the complementary
      systems account and highlight the importance of the arbitrariness/systematicity
      dimension in the consolidation process for declarative memories. 

PMID- 27046023
TI  - Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic
      Factors.
AB  - BACKGROUND/AIMS: To enable the diagnosis of moyamoya disease (MMD), detection of
      distal internal carotid artery stenosis and hazy network of basal collaterals
      (BCs) are required. This study aimed at evaluating the factors that could
      determine the degree of BCs in patients with angiographically confirmed MMD.
      METHODS: We analyzed 146 consecutive patients with MMD (age 26.2 +/- 19.6, range
      1-75). The degree of BCs (%) was measured based on conventional angiography.
      Factors associated with the degree of BCs, including clinico-radiological and
      genetic factors (p.Arg4810Lys variant), were analyzed. RESULTS: The degree of BCs
      varied among MMD patients and significantly decreased with an increase in the age
      of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC
      development depends on the MMD stage (Suzuki stage), it is less prominent in
      adult-onset (>18 years) MMD compared to childhood MMD. The presence of
      p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke
      (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of
      intracranial vessels, external carotid collateral status, and cortical
      neovascularization were not associated with the degree of BCs. CONCLUSION:
      Although prominent BCs are required for diagnosis of MMD, BCs are decreased with
      aging, suggesting that angiogenic capacity is altered in adult onset MMD compared
      to childhood MMD.

PMID- 27046024
TI  - Molecular Dynamics Simulations to Investigate the Influences of Amino Acid
      Mutations on Protein Three-Dimensional Structures of Cytochrome P450 2D6.1, 2,
      10, 14A, 51, and 62.
AB  - Many natural mutants of the drug metabolizing enzyme cytochrome P450 (CYP) 2D6
      have been reported. Because the enzymatic activities of many mutants are
      different from that of the wild type, the genetic polymorphism of CYP2D6 plays an
      important role in drug metabolism. In this study, the molecular dynamics
      simulations of the wild type and mutants of CYP2D6, CYP2D6.1, 2, 10, 14A, 51, and
      62 were performed, and the predictions of static and dynamic structures within
      them were conducted. In the mutant CYP2D6.10, 14A, and 61, dynamic properties of
      the F-G loop, which is one of the components of the active site access channel of
      CYP2D6, were different from that of the wild type. The F-G loop acted as the
      "hatch" of the channel, which was closed in those mutants. The structure of
      CYP2D6.51 was not converged by the simulation, which indicated that the three
      dimensional structure of CYP2D6.51 was largely different from that of the wild
      type. In addition, the intramolecular interaction network of CYP2D6.10, 14A, and
      61 was different from that of the wild type, and it is considered that these
      structural changes are the reason for the decrease or loss of enzymatic
      activities. On the other hand, the static and dynamic properties of CYP2D6.2,
      whose activity was normal, were not considerably different from those of the wild
      type. 

PMID- 27046025
TI  - In vitro cultures of Bacopa monnieri and an analysis of selected groups of
      biologically active metabolites in their biomass.
AB  - CONTEXT: Bacopa monnieri L. Pennell (Scrophulariaceae) is one of the most
      important plants in the system of Indian medicine (Ayurveda). OBJECTIVE: This
      paper studies the optimal growth of B. monnieri for effective accumulation of
      metabolites. Biomass growth of this plant could be accomplished in liquid
      cultures on Murashige & Skoog medium. MATERIALS AND METHODS: Powdered shoots of
      in vitro cultures of B. monnieri were extracted by methanol for indole compounds,
      phenolic compounds and bacosides for RP-HPLC analysis. Fatty acid analysis was
      performed via gas chromatography. Anti-inflammatory effect of B. monnieri
      extracts was evaluated in the A549 cells. COX-2 and cPGES expression was analyzed
      using Western blots. RESULTS: l-Tryptophan and serotonin were found in biomass
      from in vitro cultures of B. monnieri on MS medium and in biomass from the MS
      mediums enriched with the different additions such as of 0.1 g/L magnesium
      sulphate, 0.1 g/L zinc hydroaspartate, 0.1 g/L l-tryptophan, 0.25 g/L serine, 0.5
      g/L serine and 0.5 mg/L anthranilic acid. The content of l-tryptophan and
      serotonin compounds was significant in biomass from medium with the addition of
      0.1 g/L zinc hydroaspartate (0.72 mg/g dry weight and 1.19, respectively).
      Phenolic compounds identified in biomass from the same variants of MS medium were
      chlorogenic acid (ranging from 0.20 to 0.70 mg/g dry weight), neochlorogenic acid
      (ranging from 0.11 to 0.40 mg/g dry weight) and caffeic acid (ranging from 0.01
      to 0.04 mg/g dry weight). The main group of fatty acids in biomass was saturated
      fatty acids (53.4%). The predominant fatty acid was palmitic acid. A significant
      decrease of COX-2 and cPGES expression was observed in the A549 cells activated
      with LPS and treated with B. monnieri extracts. DISCUSSION AND CONCLUSIONS: As
      far as we know, this is the first analysis of indole compounds and phenolic acids
      in this plant. The multi-therapeutic effect of B. monnieri is expressed by the
      activity of bacosides. Information about the presence of indole and phenolic
      compounds, and fatty acids in this plant is limited, but the content of these
      compounds might participate in the physiological activity of B. monnieri.

PMID- 27046026
TI  - Anti-Inflammatory and Antinociceptive Properties of Flavonoids from the Fruits of
      Black Mulberry (Morus nigra L.).
AB  - We analyzed the anti-inflammatory and antinociceptive activities of total
      flavonoids (TF) found in black mulberry fruits. The TF content was 20.9 mg/g (dry
      weight). Two anthocyanins, cyanidin-3-O-glucoside (8.3 mg/g) and cyanidin-3-O
      rutinoside (2.9 mg/g), were identified in the fruits by UPLC. The TF of black
      mulberry fruits had significant reducing power and radical (OH(-), O2(.-), DPPH
      and ABTS) scavenging activities that was demonstrated in a dose-response curve.
      The TF had inhibitory activities on xylene-induced ear edema and carrageenan
      induced paw edema in mice. In addition, TF had antinociceptive activities in the
      two nociceptive phases of formalin test. We used ELISA to detect the pro
      inflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma, and NO in the serum of
      mice. These cytokines were significantly inhibited or scavenged by TF (50 and 100
      mg/kg). The results demonstrated that TF of black mulberry possess anti
      inflammatory and analgesic effects that might correlate to its antioxidant
      activities and inhibition of pro-inflammatory cytokines.

PMID- 27046027
TI  - Chenggangzhangella methanolivorans gen. nov., sp. nov., a member of the family
      Methylocystaceae, transfer of Methylopila helvetica Doronina et al. 2000 to
      Albibacter helveticus comb. nov. and emended description of the genus Albibacter.
AB  - A Gram-stain-negative, rod-shaped, non-motile and aerobic bacterial strain,
      designated CHL1T, was isolated from a sludge sample collected from a sewage
      treatment tank of an agricultural chemical factory. The strain grew at salinities
      of 0.5-5 % (w/v) NaCl (optimum 2.5 %). Growth occurred at pH 6.0-8.0 (optimum pH
      7.0) and 5-40  degrees C (optimum 28-30  degrees C). The genomic DNA G+C content
      was determined to be 70.4 mol%. Q-10 was detected as the respiratory quinone. The
      major fatty acids (>10 %) were C18 : 1omega7c and/or C18 : 1omega6c and C16 : 0.
      The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylcholine, two unidentified phospholipids and two unidentified
      aminophospholipids. Phylogenetic analyses based on 16S rRNA gene sequences showed
      that strain CHL1T formed a distinct clade with Albibacter methylovorans DSM
      22840T and Methylopila helvetica DM9T within the family Methylocystaceae. On the
      basis of phenotypic, chemotaxonomic and phylogenetic characteristics, the strain
      merits recognition as a representative of a novel species of a new genus within
      the family Methylocystaceae, for which the name Chenggangzhangella
      methanolivorans gen. nov., sp. nov. is proposed. The type strain of the type
      species is CHL1T (=KCTC 42661T=CCTCC AB 2015175T). In addition, the species
      Methylopila helveticaDoronina et al. (2000) is proposed to be transferred to the
      genus Albibacter as Albibacterhelveticus comb. nov. (type strain DM9T=CIP
      106788=VKM B-2189) on the basis of the phylogenetic analysis. An emended
      description of the genus Albibacter is also provided. 

PMID- 27046028
TI  - Rational synthesis of an exceptionally stable Zn(II) metal-organic framework for
      the highly selective and sensitive detection of picric acid.
AB  - Based on an organic ligand involving both carboxylate and tetrazole groups, a
      chemically stable Zn(II) metal-organic framework has been rationally synthesized
      and behaves as a fluorescence chemosensor for the highly selective and sensitive
      detection of picric acid, an extremely hazardous and strong explosive.

PMID- 27046029
TI  - Methadone Maintenance Treatment Promotes Referral and Uptake of HIV Testing and
      Counselling Services amongst Drug Users and Their Partners.
AB  - BACKGROUND: Methadone maintenance treatment (MMT) reduces HIV risk behaviors and
      improves access to HIV-related services among drug users. In this study, we
      assessed the uptake and willingness of MMT patients to refer HIV testing and
      counseling (HTC) service to their sexual partners and relatives. METHODS: Health
      status, HIV-related risk behaviors, and HTC uptake and referrals of 1,016 MMT
      patients in Hanoi and Nam Dinh were investigated. Willingness to pay (WTP) for
      HTC was elicited using a contingent valuation technique. Interval and logistic
      regression models were employed to determine associated factors. RESULTS: Most of
      the patients (94.2%) had received HTC, 6.6 times on average. The proportion of
      respondents willing to refer their partners, their relatives and to be voluntary
      peer educators was 45.7%, 35.3%, and 33.3%, respectively. Attending MMT
      integrated with HTC was a facilitative factor for HTC uptake, greater WTP, and
      volunteering as peer educators. Older age, higher education and income, and HIV
      positive status were positively related to willingness to refer partners or
      relatives, while having health problems (mobility, usual care, pain/discomfort)
      was associated with lower likelihood of referring others or being a volunteer.
      Over 90% patients were willing to pay an average of US $17.9 for HTC service.
      CONCLUSION: The results highlighted the potential role of MMT patients as
      referrers to HTC and voluntary peer educators. Integrating HIV testing with MMT
      services and applying users' fee are potential strategies to mobilize resources
      and encourage HIV testing among MMT patients and their partners.

PMID- 27046030
TI  - Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in
      the Earliest Stages of Infectious Disease Outbreaks.
AB  - We assess how presymptomatic infection affects predictability of infectious
      disease epidemics. We focus on whether or not a major outbreak (i.e. an epidemic
      that will go on to infect a large number of individuals) can be predicted
      reliably soon after initial cases of disease have appeared within a population.
      For emerging epidemics, significant time and effort is spent recording
      symptomatic cases. Scientific attention has often focused on improving
      statistical methodologies to estimate disease transmission parameters from these
      data. Here we show that, even if symptomatic cases are recorded perfectly, and
      disease spread parameters are estimated exactly, it is impossible to estimate the
      probability of a major outbreak without ambiguity. Our results therefore provide
      an upper bound on the accuracy of forecasts of major outbreaks that are
      constructed using data on symptomatic cases alone. Accurate prediction of whether
      or not an epidemic will occur requires records of symptomatic individuals to be
      supplemented with data concerning the true infection status of apparently
      uninfected individuals. To forecast likely future behavior in the earliest stages
      of an emerging outbreak, it is therefore vital to develop and deploy accurate
      diagnostic tests that can determine whether asymptomatic individuals are actually
      uninfected, or instead are infected but just do not yet show detectable symptoms.

PMID- 27046032
TI  - Frequency of takeaway food consumption and its association with major food group
      consumption, anthropometric measures and blood pressure during adolescence.
AB  - We prospectively assessed the (1) frequency and socio-economic correlates of
      takeaway food consumption during adolescence; and (2) association between
      frequent takeaway food consumption with intakes of major food groups and
      anthropometric measures and blood pressure (BP). In total, 699 Sydney
      schoolchildren (380 girls and 319 boys) who had dietary data at both 12 and 17
      years of age were included for analyses. Takeaway food consumption was self
      reported and based on a single question. Anthropometric measures and BP were
      collected. The proportion of participants who ate takeaway foods once per week or
      more increased significantly over 5 years from the age of 12 to 17 years: 35.5
      44.1 % (P<0.0001). In total, 12-year-old girls compared with boys had reduced
      odds of takeaway foods once per week or more at the age of 17 years (P=0.01),
      multivariable-adjusted OR 0.63 (95 % CI 0.44, 0.90). In total, 12-year-old
      children who ate takeaway foods once per week or more had significantly lower
      mean fruit (220.3 v. 253.0 g/d; P=0.03) and vegetable consumption (213.2 v. 247.7
      g/d; P=0.004), 5 years later (at 17 years of age). Frequent takeaway food
      consumption at the age of 12 years was not associated with anthropometric indices
      and BP at the age of 17 years. Consumption of takeaway foods became more frequent
      during adolescence, particularly among boys, and it was associated with reduced
      intake of fruits and vegetables.

PMID- 27046033
TI  - Acute Orbital Syndrome in Herpes Zoster Ophthalmicus: Clinical Features of 7
      Cases.
AB  - PURPOSE: To report a series of patients with herpes zoster ophthalmicus and
      associated acute orbital syndrome with corresponding radiographic findings.
      METHODS: Medical records of 7 patients with herpes zoster ophthalmicus with acute
      orbital findings were reviewed. Clinical presentation, radiography, and treatment
      outcomes were assessed. RESULTS: One man and 6 women with a median age of 70
      years (range 47-84) presented with herpes zoster ophthalmicus with acute clinical
      orbital signs. Two of the 7 patients had compromised immune systems, with 1
      patient having chronic lymphocytic leukemia and another infected with human
      immunodeficiency virus. Clinical orbital findings included proptosis,
      blepharoptosis, ophthalmoplegia, diplopia, and visual loss. Orbital imaging
      detailed such findings as myositis in all 7 patients, dacryoadenitis in 2
      patients, and optic nerve sheath enhancement in 1 patient. Treatment with
      intravenous acyclovir was universal in all 7 patients and in 2 cases systemic
      corticosteroids were also administered. Orbital signs improved in all patients
      over several months. CONCLUSIONS: Herpes zoster ophthalmicus can rarely cause an
      acute orbital syndrome and the authors present what may be the largest series of
      such patients to date. Herpes zoster ophthalmicus can affect various orbital
      structures including the lacrimal gland, extraocular muscles, cranial nerves and
      optic nerve sheath. A careful clinical examination and detailed orbital
      radiography are critical in proper diagnosis and treatment of such patients.
      Improvement of symptoms and signs with antiviral therapy can be expected;
      however, complete resolution does not always occur. The role of systemic steroids
      in treatment of orbital disease is yet to be determined.

PMID- 27046031
TI  - Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during
      Intracellular Infection.
AB  - Intracellular colonization and persistent infection by the kinetoplastid
      protozoan parasite, Trypanosoma cruzi, underlie the pathogenesis of human Chagas
      disease. To obtain global insights into the T. cruzi infective process,
      transcriptome dynamics were simultaneously captured in the parasite and host
      cells in an infection time course of human fibroblasts. Extensive remodeling of
      the T. cruzi transcriptome was observed during the early establishment of
      intracellular infection, coincident with a major developmental transition in the
      parasite. Contrasting this early response, few additional changes in steady state
      mRNA levels were detected once mature T. cruzi amastigotes were formed. Our
      findings suggest that transcriptome remodeling is required to establish a
      modified template to guide developmental transitions in the parasite, whereas
      homeostatic functions are regulated independently of transcriptomic changes,
      similar to that reported in related trypanosomatids. Despite complex mechanisms
      for regulation of phenotypic expression in T. cruzi, transcriptomic signatures
      derived from distinct developmental stages mirror known or projected
      characteristics of T. cruzi biology. Focusing on energy metabolism, we were able
      to validate predictions forecast in the mRNA expression profiles. We demonstrate
      measurable differences in the bioenergetic properties of the different mammalian
      infective stages of T. cruzi and present additional findings that underscore the
      importance of mitochondrial electron transport in T. cruzi amastigote growth and
      survival. Consequences of T. cruzi colonization for the host include dynamic
      expression of immune response genes and cell cycle regulators with upregulation
      of host cholesterol and lipid synthesis pathways, which may serve to fuel
      intracellular T. cruzi growth. Thus, in addition to the biological inferences
      gained from gene ontology and functional enrichment analysis of differentially
      expressed genes in parasite and host, our comprehensive, high resolution
      transcriptomic dataset provides a substantially more detailed interpretation of
      T. cruzi infection biology and offers a basis for future drug and vaccine
      discovery efforts. 

PMID- 27046034
TI  - Childhood Optic Nerve Glioma: Vision Loss Due to Biopsy.
AB  - Two children without neurofibromatosis type 1 presented with unilateral decreased
      vision and MRI revealing optic nerve tumors. In the first case, chemotherapy was
      initiated empirically for presumed optic pathway glioma, but the lesion increased
      in size with associated clinical worsening, raising concern for a possible
      alternate diagnosis. Biopsy of the involved optic nerve resulted in worsening of
      vision due to a branch retinal artery occlusion and showed a grade I pilocytic
      astrocytoma. In the second case, sudden symptom onset and rapid tumor growth
      prompted an optic nerve biopsy, resulting in vision loss due to a central retinal
      artery occlusion and revealing grade I pilocytic astrocytoma. In both cases,
      tissue diagnosis did not alter the course of management. Instead, biopsy was
      associated with additional vision loss, highlighting the risk of biopsy in
      children with isolated optic nerve tumors and imaging that is most consistent
      with an optic pathway glioma.

PMID- 27046035
TI  - Aspergillus Mycetoma Causing Epiphora and Ipsilateral Facial Pain.
AB  - Tearing is a frequently encountered chief complaint in an ophthalmologist's
      office. Certain associated atypical symptoms may warrant further workup. The
      authors present a case of a patient presenting with painful tearing which
      elicited further evaluation with CT imaging. This revealed a maxillary sinus
      fungus ball as the cause for the patient's tearing.

PMID- 27046036
TI  - Endoscopic Medial Rectus Sling: A Window Into the Intraconal Orbital Apex.
AB  - PURPOSE: Surgical approaches to the medial orbit especially within the cone of
      orbital muscles necessitate great precision and care to avoid damage to
      surrounding structures-most importantly the optic nerve. The authors present a
      novel technique in which access to the medial orbital contents was achieved
      through an entirely endoscopic approach. METHODS: A 72-year-old Caucasian female
      presented with loss of vision in the right eye and reduced extraocular movements.
      Baseline blood tests were within normal limits. Inflammatory markers were
      slightly elevated. CT scan revealed bilateral medial orbital apex masses. Biopsy
      of the right orbital apex lesion was performed through an exclusively endoscopic
      approach in which the medial rectus muscle was retracted infero-medially.
      RESULTS: This exclusively endonasal approach to the medial intraconal space
      provided excellent access to the orbital apex, thus allowing successful biopsy of
      the medial orbital apex lesion. A video of the surgical technique demonstrates
      its use in this patient (see Video, Supplemental Digital Content 1, available at
      http://links.lww.com/IOP/A123). CONCLUSIONS: Similar reports of endonasal
      medialization of the medial rectus for accessing intraconal orbital lesions have
      been previously described in the rhinological literature. The authors describe a
      modification that allows for a safe and less invasive approach to the medial
      intraconal space and intraorbital optic nerve. There is minimal trauma to the
      surrounding tissues and no further damage to the optic nerve along with no
      associated adverse clinical sequelae. In addition, this negates the need for an
      adjuvant external or transconjunctival approach.

PMID- 27046037
TI  - Orbital Compartment Syndrome Following Post-Traumatic Subgaleal Hematoma.
AB  - Orbital extension of subgaleal hematoma is rare. This report describes the case
      of an otherwise healthy 10-year-old girl who developed delayed contralateral
      proptosis and external ophthalmoplegia after relatively minor right-sided
      forehead trauma. She was found to have bilateral subgaleal hematomas
      communicating with a left superior subperiostial orbital hematoma. Over the
      course of 2 days, she developed an orbital compartment syndrome requiring
      emergent canthotomy and cantholysis, followed by surgical incision and drainage
      of her scalp hematoma without orbitotomy. Hematologic work-up revealed
      heterozygous factor VII deficiency.

PMID- 27046038
TI  - Orbital Plasmacytoma Mimicking an Orbital Abscess.
AB  - An 83-year-old male with a 15-month history of multiple myeloma presented with
      acute onset of swelling, redness, and pain around his right eye. CT scan was
      consistent with an orbital abscess. The patient was taken to the operating room
      for drainage of the orbital abscess. Abnormal tissue was encountered
      intraoperatively so biopsies were taken. His cultures grew only one colony of
      coagulase-negative Staphylococcus aureus. The histopathology from the biopsies
      showed a CD-138 positive plasma cell neoplasia consistent with a plasmacytoma.
      Plasmacytomas have been reported to present as orbital cellulitis and as
      abscesses in other locations in the body, but to our knowledge, this is the first
      case of a plasmacytoma presenting as an orbital abscess.

PMID- 27046039
TI  - Correction of Lower Eyelid Retraction Using Acellular Human Dermis During Orbital
      Decompression.
AB  - PURPOSE: To investigate the surgical outcome of grafting acellular human dermis
      compared with concurrent lower eyelid retractor recession during swinging eyelid
      orbital decompression for correction of lower eyelid retraction in patients with
      Graves' orbitopathy. METHODS: Institutional Review Board-approved retrospective
      nonrandomized study of 54 Graves' orbitopathy patients (95 eyes) from 2008 to
      2012. Patients who received decompression were divided into 3 groups: Group 1
      with conjunctival lengthening using 0.3-mm thickness AlloDerm (36 eyes), Group 2
      with inferior retractor recession (33 eyes), and Group 3 with decompression only
      (26 eyes). Outcome measures included lower eyelid height, inferior sclera show,
      cosmetic appearance, and complications. RESULTS: Baseline clinical
      characteristics and the degree of improvement of exophthalmos were not different
      between groups. Preoperative MRD2 was higher in group 1 (8.0 mm) than in groups 2
      (6.9 mm, p < 0.001) and 3 (6.6 mm, p < 0.001). Mean improvement of MRD2 as well
      as postoperative improvement of inferior scleral show at postoperative 4 to 6
      months were significantly higher in group 1 (2.7 mm) than in groups 2 (1.8 mm, p
      < 0.001) and 3 (1.2 mm, p < 0.001). CONCLUSION: Simultaneous correction of lower
      eyelid retraction using thin AlloDerm during swinging eyelid orbital
      decompression maximizes improvement of lower eyelid retraction compared with
      concurrent inferior retractor recession.

PMID- 27046041
TI  - Enzyme oscillation can enhance the thermodynamic efficiency of cellular
      metabolism: consequence of anti-phase coupling between reaction flux and
      affinity.
AB  - Cells generally convert nutrient resources to products via energy transduction.
      Accordingly, the thermodynamic efficiency of this conversion process is one of
      the most essential characteristics of living organisms. However, although these
      processes occur under conditions of dynamic metabolism, most studies of cellular
      thermodynamic efficiency have been restricted to examining steady states; thus,
      the relevance of dynamics to this efficiency has not yet been elucidated. Here,
      we develop a simple model of metabolic reactions with anabolism-catabolism
      coupling catalyzed by enzymes. Through application of external oscillation in the
      enzyme abundances, the thermodynamic efficiency of metabolism was found to be
      improved. This result is in strong contrast with that observed in the oscillatory
      input, in which the efficiency always decreased with oscillation. This
      improvement was effectively achieved by separating the anabolic and catabolic
      reactions, which tend to disequilibrate each other, and taking advantage of the
      temporal oscillations so that each of the antagonistic reactions could progress
      near equilibrium. In this case, anti-phase oscillation between the reaction flux
      and chemical affinity through oscillation of enzyme abundances is essential. This
      improvement was also confirmed in a model capable of generating autonomous
      oscillations in enzyme abundances. Finally, the possible relevance of the
      improvement in thermodynamic efficiency is discussed with respect to the
      potential for manipulation of metabolic oscillations in microorganisms. 

PMID- 27046040
TI  - Phosphorylated Heat Shock Protein 20 (HSPB6) Regulates Transforming Growth Factor
      alpha-Induced Migration and Invasion of Hepatocellular Carcinoma Cells.
AB  - Human hepatocellular carcinoma (HCC) is one of the major malignancies in the
      world. Small heat shock proteins (HSPs) are reported to play an important role in
      the regulation of a variety of cancer cell functions, and the functions of small
      HSPs are regulated by post-translational modifications such as phosphorylation.
      We previously reported that protein levels of a small HSP, HSP20 (HSPB6),
      decrease in vascular invasion positive HCC compared with those in the negative
      vascular invasion. Therefore, in the present study, we investigated whether HSP20
      is implicated in HCC cell migration and the invasion using human HCC-derived HuH7
      cells. The transforming growth factor (TGF)-alpha-induced migration and invasion
      were suppressed in the wild-type-HSP20 overexpressed cells in which
      phosphorylated HSP20 was detected. Phospho-mimic-HSP20 overexpression reduced the
      migration and invasion compared with unphosphorylated HSP20 overexpression.
      Dibutyryl cAMP, which enhanced the phosphorylation of wild-type-HSP20,
      significantly reduced the TGF-alpha-induced cell migration of wild-type HSP20
      overexpressed cells. The TGF-alpha-induced cell migration was inhibited by
      SP600125, a c-Jun N-terminal kinases (JNK) inhibitor. In phospho-mimic-HSP20
      overexpressed HuH7 cells, TGF-alpha-stimulated JNK phosphorylation was suppressed
      compared with the unphosphorylated HSP20 overexpressed cells. Moreover, the level
      of phospho-HSP20 protein in human HCC tissues was significantly correlated with
      tumor invasion. Taken together, our findings strongly suggest that phosphorylated
      HSP20 inhibits TGF-alpha-induced HCC cell migration and invasion via suppression
      of the JNK signaling pathway. 

PMID- 27046042
TI  - Effects of a High-Fat or High-Sucrose Diet on Ultraviolet B Irradiation-Induced
      Carcinogenesis and Tumor Growth in Melanin-Possessing Hairless Mice.
AB  - We herein compared the effects of the chronic feeding of high-fat (HF), high
      sucrose (HS), and low-fat/low-sucrose (control) diets on carcinogenesis following
      chronic ultraviolet B (UVB) irradiation in hairless mice. UVB irradiation-induced
      carcinogenesis was more prominent in HF diet-fed group than in control diet- and
      HS diet-fed groups. The HS diet group, as well as the HF diet one, showed tumor
      development and growth, increased skin matrix metalloproteinase (MMP) and blood
      plasminogen activator inhibitor-1 (PAI-1) levels, and decreased blood leptin and
      adiponectin levels after long-term UVB irradiation. These changes were smaller in
      the HS diet group than in the HF diet group. In addition, no difference was noted
      in the above changes between the control and HS diet groups. The increase induced
      in adipose tissue weight by the HF diet was markedly reduced by UVB irradiation.
      This result suggests that the abundant availability of lipids in hypertrophic
      adipose tissue may be related to tumor incidence and growth through increases in
      blood PAI-1 and skin MMP-9 expression levels and decreases in blood adiponectin
      levels by UVB irradiation. In conclusion, HF diet-induced hypertrophic adipose
      tissue is an important cancer risk factor that promotes UV irradiation-induced
      carcinogenesis and tumor growth.

PMID- 27046043
TI  - Segregated Ice Growth in a Suspension of Colloidal Particles.
AB  - We study the freezing of a dispersion of colloidal silica particles in water,
      focusing on the formation of segregated ice in the form of ice lenses. Local
      temperature measurements in combination with video microscopy give insight into
      the rich variety of factors that control ice lens formation. We observe the
      initiation of the lenses, their growth morphology, and their final thickness and
      spacing over a range of conditions, in particular the effect of the particle
      packing and the cooling rate. We find that increasing the particle density
      drastically reduces the thickness of lenses but has little effect on the lens
      spacing. Therefore, the fraction of segregated ice formed reduces. The effect of
      the cooling rate, which is the product of the temperature gradient and the
      pulling speed across the temperature gradient, depends on which parameter is
      varied. A larger temperature gradient causes ice lenses to be initiated more
      frequently, while a lower pulling speed allows for more time for ice lenses to
      grow: both increase the fraction of segregated ice. Surprisingly, we find that
      the growth rate of a lens does not depend on its undercooling. Finally, we have
      indications of pore ice in front of the warmest ice lens, which has important
      consequences for the interpretation of the measured trends. Our findings are
      relevant for ice segregation occurring in a wide range of situations, ranging
      from model lab experiments and theories to geological and industrial processes,
      like frost heave and frozen food production.

PMID- 27046044
TI  - Re: The impact of sarcopenia and myosteatosis on outcomes of unresectable
      pancreatic cancer or distal cholangiocarcinoma.

PMID- 27046045
TI  - Poly(ionic liquid)/Ionic Liquid Ion-Gels with High "Free" Ionic Liquid Content:
      Platform Membrane Materials for CO2/Light Gas Separations.
AB  - The recycling or sequestration of carbon dioxide (CO2) from the waste gas of
      fossil-fuel power plants is widely acknowledged as one of the most realistic
      strategies for delaying or avoiding the severest environmental, economic,
      political, and social consequences that will result from global climate change
      and ocean acidification. For context, in 2013 coal and natural gas power plants
      accounted for roughly 31% of total U.S. CO2 emissions. Recycling or sequestering
      this CO2 would reduce U.S. emissions by ca. 1800 million metric tons-easily
      meeting the U.S.'s currently stated CO2 reduction targets of ca. 17% relative to
      2005 levels by 2020. This situation is similar for many developed and developing
      nations, many of which officially target a 20% reduction relative to 1990
      baseline levels by 2020. To make CO2 recycling or sequestration processes
      technologically and economically viable, the CO2 must first be separated from the
      rest of the waste gas mixture-which is comprised mostly of nitrogen gas and water
      (ca. 85%). Of the many potential separation technologies available, membrane
      technology is particularly attractive due to its low energy operating cost, low
      maintenance, smaller equipment footprint, and relatively facile retrofit
      integration with existing power plant designs. From a techno-economic standpoint,
      the separation of CO2 from flue gas requires membranes that can process extremely
      high amounts of CO2 over a short time period, a property defined as the membrane
      "permeance". In contrast, the membrane's CO2/N2 selectivity has only a minor
      effect on the overall cost of some separation processes once a threshold
      permeability selectivity of ca. 20 is reached. Given the above criteria, the
      critical properties when developing membrane materials for postcombustion CO2
      separation are CO2 permeability (i.e., the rate of CO2 transport normalized to
      the material thickness), a reasonable CO2/N2 selectivity (>=20), and the ability
      to be processed into defect-free thin-films (ca. 100-nm-thick active layer).
      Traditional polymeric membrane materials are limited by a trade-off between
      permeability and selectivity empirically described by the "Robeson upper bound"
      placing the desired membrane properties beyond reach. Therefore, the
      investigation of advanced and composite materials that can overcome the
      limitations of traditional polymeric materials is the focus of significant
      academic and industrial research. In particular, there has been substantial work
      on ionic-liquid (IL)-based materials due to their gas transport properties. This
      review provides an overview of our collaborative work on developing poly(ionic
      liquid)/ionic liquid (PIL/IL) ion-gel membrane technology. We detail
      developmental work on the preparation of PIL/IL composites and describe how this
      chemical technology was adapted to allow the roll-to-roll processing and
      preparation of membranes with defect-free active layers ca. 100 nm thick, CO2
      permeances of over 6000 GPU, and CO2/N2 selectivity of >=20-properties with the
      potential to reduce the cost of CO2 removal from coal-fired power plant flue gas
      to ca. $15 per ton of CO2 captured. Additionally, we examine the materials
      developments that have produced advanced PIL/IL composite membranes. These
      advancements include cross-linked PIL/IL blends, step-growth PIL/IL networks with
      facilitated transport groups, and PIL/IL composites with microporous additives
      for CO2/CH4 separations. 

PMID- 27046046
TI  - Synthesis of Cone-Shaped Colloids from Rod-Like Silica Colloids with a Gradient
      in the Etching Rate.
AB  - We present the synthesis of monodisperse cone-shaped silica colloids and their
      fluorescent labeling. Rod-like silica colloids prepared by ammonia-catalyzed
      hydrolysis and condensation of tetraethyl orthosilicate in water droplets
      containing polyvinylpyrrolidone cross-linked by citrate ions in pentanol were
      found to transform into cone-shaped particles upon mild etching by NaOH in water.
      The diameter and length of the resulting particles were determined by those of
      the initial rod-like silica colloids. The mechanism responsible for the cone
      shape involves silica etching taking place with a varying rate along the length
      of the particle. Our experiments thus also lead to new insights into the
      variation of the local particle structure and composition. These are found to
      vary gradually along the length of the rod, as a result of the way the rod grows
      out of a water droplet that keeps itself attached to the flat end of the bullet
      shaped particles. Subtle differences in composition and structure could also be
      resolved by high-resolution stimulated emission depletion confocal microscopy on
      fluorescently labeled particles. The incorporation of a fluorescent dye
      chemically attached to an amine-based silane coupling agent resulted in a
      distribution of fluorophores mainly on the outside of the rod-shaped particles.
      In contrast, incorporation of the silane coupling agent alone resulted in a
      homogeneous distribution. Additionally, we show that etching rods, where a silane
      coupling agent alone was incorporated and subsequently coupled to a fluorescent
      dye, resulted in fluorescent silica cones, the orientation of which can be
      discerned using super-resolution confocal microscopy.

PMID- 27046047
TI  - [The anticipated directives will prove a liberation leading to mutual
      commitment].

PMID- 27046048
TI  - Buckwheat phenolic metabolites in health and disease.
AB  - Buckwheat (Fagopyrum esculentum Moench, F. tataricum Gaertner) groats and flour
      have been established globally as nutritional foods because of their high levels
      of proteins, polyphenols and minerals. In some regions, buckwheat herb is used as
      a functional food. In the present study, reports of in vitro studies, preclinical
      and clinical trials dealing with the effect of buckwheat and its metabolites were
      reviewed. There are numerous reports of potential health benefits of consuming
      buckwheat, which may be in the form of food, dietary supplements, home remedies
      or possibly pharmaceutical drugs; however, adverse effects, including those
      resulting from contamination, must be considered. There are reports of
      antioxidative activity of buckwheat, which contains high levels of rutin and
      quercetin. On the other hand, both cytotoxic and antigenotoxic effects have been
      shown. Reduction of hyperlipidaemia, reduction of blood pressure and improved
      weight regulation have been suggested. Consuming buckwheat may have a beneficial
      effect on diabetes, since lower postprandial blood glucose and insulin response
      have been reported. In addition, buckwheat metabolites, such as rutin, may have
      intrinsic protective effects in preserving insulin signalling. Rutin has also
      been suggested to have potential therapeutic applications for the treatment of
      Alzheimer's disease. The literature indicates that buckwheat is safe to consume
      and may have various beneficial effects on human health. 

PMID- 27046049
TI  - Predictors of radiation-induced gastrointestinal morbidity: A prospective,
      longitudinal study following radiotherapy for carcinoma of the prostate.
AB  - Background Chronic gastrointestinal (GI) morbidity occurs in >=50% of patients
      after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This
      prospective, longitudinal study examines which baseline measurements of: 1)
      homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair
      biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after
      EBRT. Patients and methods In total, 106 patients with CaP had evaluations of GI
      symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one,
      two and three years after its completion. Other variables measured before EBRT
      were: 1) plasma concentrations of homocysteine and micronutrients including
      caroteinoids and selenium; 2) chromosome damage/DNA misrepair
      (micronuclei/nucleoplasmic bridge) indices; and 3) mean anal and rectal wall
      doses and volumes of anal and rectal walls receiving >=40 Gy and >=60 Gy.
      Univariate and multivariate analyzes examined the relationships among: 1) plasma
      levels of homocysteine and micronutrients; 2) indices of chromosome damage/DNA
      misrepair; and 3) mean anal and rectal wall doses and volumes of anal and rectal
      walls receiving >=40 Gy and >=60 Gy and total GI symptom scores from one month to
      three years after EBRT. Results Increased frequency and urgency of defecation,
      rectal mucous discharge and bleeding after EBRT resulted in sustained rises in
      total GI symptom scores above baseline at three years. On univariate analysis,
      total GI symptom scores were significantly associated with: 1) plasma selenium
      and alpha tocopherol; 2) micronuclei indices of DNA damage; 3) mean anal and
      rectal wall doses; and 4) volumes of anal and rectal wall receiving >=40 Gy and
      >=60 Gy (p = 0.08-<0.001). On multivariate analysis, only volume of anal wall
      receiving >=40 Gy was significant for increased GI symptoms after EBRT (p <
      0.001). Conclusion The volume of anal wall receiving >=40 Gy predicts chronic GI
      morbidity after EBRT for CaP. 

PMID- 27046050
TI  - CASP11--An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction
      Pipeline.
AB  - In silico prediction of a protein's tertiary structure remains an unsolved
      problem. The community-wide Critical Assessment of Protein Structure Prediction
      (CASP) experiment provides a double-blind study to evaluate improvements in
      protein structure prediction algorithms. We developed a protein structure
      prediction pipeline employing a three-stage approach, consisting of low
      resolution topology search, high-resolution refinement, and molecular dynamics
      simulation to predict the tertiary structure of proteins from the primary
      structure alone or including distance restraints either from predicted residue
      residue contacts, nuclear magnetic resonance (NMR) nuclear overhauser effect
      (NOE) experiments, or mass spectroscopy (MS) cross-linking (XL) data. The protein
      structure prediction pipeline was evaluated in the CASP11 experiment on twenty
      regular protein targets as well as thirty-three 'assisted' protein targets, which
      also had distance restraints available. Although the low-resolution topology
      search module was able to sample models with a global distance test total score
      (GDT_TS) value greater than 30% for twelve out of twenty proteins, frequently it
      was not possible to select the most accurate models for refinement, resulting in
      a general decay of model quality over the course of the prediction pipeline. In
      this study, we provide a detailed overall analysis, study one target protein in
      more detail as it travels through the protein structure prediction pipeline, and
      evaluate the impact of limited experimental data. 

PMID- 27046051
TI  - Structure-guided design of small-molecule therapeutics against RSV disease.
AB  - INTRODUCTION: In the United States, respiratory syncytial virus (RSV) is
      responsible for the majority of infant hospitalizations resulting from viral
      infections, as well as a leading source of pneumonia and bronchiolitis in young
      children and the elderly. In the absence of vaccine prophylaxis or an effective
      antiviral for improved disease management, the development of novel anti-RSV
      therapeutics is critical. Several advanced drug development campaigns of the past
      decade have focused on blocking viral infection. These efforts have returned a
      chemically distinct panel of small-molecule RSV entry inhibitors, but binding
      sites and molecular mechanism of action appeared to share a common mechanism,
      resulting in comprehensive cross-resistance and calling for alternative druggable
      targets such as viral RNA-dependent RNA-polymerase complex. Areas Covered: In
      this review, the authors discuss the current status of the mechanism of action of
      RSV entry inhibitors. They also provide the recent structural insight into the
      organization of the polymerase complex that have revealed novel drug targets
      sites, and outline a path towards the discovery of next-generation RSV
      therapeutics. Expert opinion: Considering the tremendous progress experienced in
      our structural understanding of RSV biology in recent years and encouraging early
      results of a nucleoside analog inhibitor in clinical trials, there is high
      prospect that new generations of much needed effective anti-RSV therapeutics will
      become available for clinical use in the foreseeable future.

PMID- 27046053
TI  - Use of TachoSil(r) to Prevent Symptomatic Lymphocele after an Aggressive Tumor
      Debulking with Lymphadenectomy for Advanced Stage Ovarian Cancer. A Pilot Study.
AB  - OBJECTIVE: To describe the incidence of symptomatic lymphocele (SLC) after an
      aggressive tumor debulking surgery and lymphadenectomy in patients with ovarian
      cancer and peritoneal carcinomatosis with or without TachoSil(r). MATERIAL AND
      METHODS: A pilot retrospective comparative observational study was performed
      between patients with advanced ovarian cancer International Federation of
      Gynecology and Obstetrics stages III-IV who underwent complete debulking surgery
      and radical retroperitoneal lymphadenectomy. In 18 patients, 4 TachoSil(r)
      patches were placed in the retroperitoneal area, since January 2014-October 2014.
      This group was compared with other 18 consecutive patients matched by age,
      International Federation of Gynecology and Obstetrics stage, surgical complexity,
      American Society of Anesthesiologists score, comorbidity, and BMI without the use
      of TachoSil(r). RESULTS: Baseline characteristics were similar between groups.
      There were no statistically significant differences in terms of surgical
      complexity, surgical time, estimated blood loss, node removed, length of hospital
      stay, and complications between groups. SLC was diagnosed in 7 patients (38.8%)
      without TachoSil(r), and in 2 patients (11.1%) with TachoSil(r) (p = 0.121). The
      use of TachoSil(r) was associated with a statistically significant lower re
      admission rate (p = 0.041) and with a significantly shorter time to adjuvant
      chemotherapy (p = 0.02). CONCLUSIONS: Using TachoSil(r) in women with advanced
      stage ovarian cancer who underwent radical debulking with retroperitoneal lymph
      node dissection is associated with a non-statistically significant reduction in
      the incidence of SLC. A larger-scale randomized controlled study should be
      conducted to confirm our preliminary results.

PMID- 27046054
TI  - Ambipolar Transport in Solution-Synthesized Graphene Nanoribbons.
AB  - Graphene nanoribbons (GNRs) with robust electronic band gaps are promising
      candidate materials for nanometer-scale electronic circuits. Realizing their full
      potential, however, will depend on the ability to access GNRs with prescribed
      widths and edge structures and an understanding of their fundamental electronic
      properties. We report field-effect devices exhibiting ambipolar transport in
      accumulation mode composed of solution-synthesized GNRs with straight armchair
      edges. Temperature-dependent electrical measurements specify thermally activated
      charge transport, which we attribute to inter-ribbon hopping. With access to
      structurally precise materials in practical quantities and by overcoming
      processing difficulties in making electrical contacts to these materials, we have
      demonstrated critical steps toward nanoelectric devices based on solution
      synthesized GNRs.

PMID- 27046055
TI  - Genome-Wide Analysis of Human Metapneumovirus Evolution.
AB  - Human metapneumovirus (HMPV) has been described as an important etiologic agent
      of upper and lower respiratory tract infections, especially in young children and
      the elderly. Most of school-aged children might be introduced to HMPVs, and
      exacerbation with other viral or bacterial super-infection is common. However,
      our understanding of the molecular evolution of HMPVs remains limited. To address
      the comprehensive evolutionary dynamics of HMPVs, we report a genome-wide
      analysis of the eight genes (N, P, M, F, M2, SH, G, and L) using 103 complete
      genome sequences. Phylogenetic reconstruction revealed that the eight genes from
      one HMPV strain grouped into the same genetic group among the five distinct
      lineages (A1, A2a, A2b, B1, and B2). A few exceptions of phylogenetic
      incongruence might suggest past recombination events, and we detected possible
      recombination breakpoints in the F, SH, and G coding regions. The five genetic
      lineages of HMPVs shared quite remote common ancestors ranging more than 220 to
      470 years of age with the most recent origins for the A2b sublineage. Purifying
      selection was common, but most protein genes except the F and M2-2 coding regions
      also appeared to experience episodic diversifying selection. Taken together,
      these suggest that the five lineages of HMPVs maintain their individual
      evolutionary dynamics and that recombination and selection forces might work on
      shaping the genetic diversity of HMPVs. 

PMID- 27046056
TI  - Short- and long-term metabolic responses to diets with different
      protein:carbohydrate ratios in Senegalese sole (Solea senegalensis, Kaup 1858).
AB  - Four isolipidic and isoenergetic diets with different protein:carbohydrate (CH)
      contents (48:38, 52:34, 56:30, 60:26) were fed to juvenile Senegalese sole (22.01
      (sem 0.01) g) during 104 d. Oral glucose tolerance tests were performed at the
      beginning (4 d) and at the end (104 d) of the experiment to assess the effect of
      the dietary treatment on glucose tolerance. Samples of blood, liver and muscle of
      all dietary groups were also obtained at the initial and final phases of the
      trial at different postprandial times (0, 1, 5 and 10 h after feeding) in order
      to analyse glucose and NEFA in plasma, and metabolites and enzyme activities
      involved in glycogen metabolism, glycolysis, gluconeogenesis and lipogenesis
      pathways in liver and muscle. The results obtained in this study suggest a good
      glucose tolerance in Senegalese sole. This species tolerated important amounts of
      CH in the diet without showing any deleterious signs in terms of growth or any
      metabolic disorders. After 104 d of feeding diets with an important amount of CH
      (48:38 and 52:34), the control of glycaemia was maintained and even postprandial
      glucose levels in plasma were (in general) lower than at the beginning of the
      experiment. This reasonable tolerance to glucose is also reflected by an
      increased use of glucose through glycolysis in liver (indicated by glucokinase
      activity), and the absence of changes in lipogenic potential in the same tissue
      (indicated by ATP citrate lyase activity). No clear changes were induced in the
      muscle by the dietary treatments.

PMID- 27046057
TI  - Multi-contrast T2(*)-relaxometry upon visual stimulation at 3T and 7T.
AB  - This study aims to quantify the mean change of the effective transverse
      relaxation time T2(*) in active brain regions of human volunteers at field
      strengths of B0=3T and 7T. Besides the mono-exponential signal decay model an
      extended model is tested that considers mesoscopic field gradients across imaging
      voxels. Both models are checked for cross-talk and correlations between the
      parameters. A visual checkerboard-stimulation experiment with pause and
      stimulation periods of 50s and six repetitions was performed on healthy
      volunteers. Eleven contrasts were acquired in about 1.47s/1.43s at 3T/7T using a
      segmented multi-contrast echo-planar imaging (EPI) sequence. Average BOLD-signal
      time courses were calculated in a multi-step (non-)linear least-squares process.
      Baseline T2(*) values of 37.72ms/24.99ms (47.34ms/33.71ms) with stimulus
      correlated changes ?T2(*)of 1.32ms/0.74ms (1.99ms/1.43ms) resulted from the mono
      exponential (extended) model for 3T/7T. A dependence of those values on the
      initial intensity S0 was observed. Stimulus-correlated changes of S0 in the order
      of 1% were measured at both field strengths. The mono-exponential model was found
      to be less prone to instabilities in the regression of both parameters. Signal
      alterations due to inflow were observed. Measured relaxation times agree with
      values from literature using repetitive stimulation. A strong dependence of the
      measured relaxation times on the inflow-related model parameter was found for
      both models. The extended model is applicable to dynamic neurofunctional
      measurements, but is currently limited due to the low number of contrasts
      acquired.

PMID- 27046058
TI  - T cell factor-4 functions as a co-activator to promote NF-kappaB-dependent MMP-15
      expression in lung carcinoma cells.
AB  - Both TCF-4 and MMP-15 are closely linked to the development of lung cancer, while
      the regulatory role of TCF-4 in MMP-15 expression is still obscure. Here we found
      that expression of TCF-4 and MMP-15 was increased in lung cancer cells or tissues
      versus the normal ones. With gain-or loss-of -function studies, we demonstrated
      that TCF-4 positively regulated MMP-15 expression in mRNA and protein levels.
      With reporter gene assay, we found that TCF-4 regulated MMP-15 expression via a
      potential NF-kappaB binding element locating at -2833/-2824 in the mouse MMP-15
      promoter. With ChIP and immunoblotting assays, we identified that TCF-4
      functioned as a co-activator to potentiate the binding between p65 and MMP-15
      promoter. Functionally, TCF-4 silence attenuated the migration activity of LLC
      cells, while additional overexpression of MMP-15 rescued this effect in cell
      scratch test and transwell migration assay. In xenograft model, TCF-4 silence
      improved tumor lesions in lungs and survival time of LLC-tumor bearing mice were
      abolished by MMP-15 overexpression. In conclusion, we are the first to identify
      TCF-4 as a co-activator of NF-kappaB p65 to promote MMP-15 transcription and
      potentiate the migration activity of the lung cancer cells. Our findings shed
      light on the therapeutic strategies of this malignancy. 

PMID- 27046059
TI  - Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea
      in Carbon Tetrachloride-Induced Liver Injury in Rat.
AB  - Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and
      has multiple biological functions, including hepatoprotective and immune
      modulatory effects. Currently, the commercially available A. cinnamomea are
      mainly liquid- and solid-state fermented A. cinnamomea. However, the
      hepatoprotective effect of solid-state fermented A. cinnamomea has never been
      reported. Here we evaluate the ability of air-dried, ground and non-extracted
      wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon
      tetrachloride (CCl4)-induced hepatic injury in vivo. The results showed that oral
      administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the
      increase in plasma aspartate aminotransferase and alanine aminotransferase levels
      caused by chronic repeated CCl4 intoxication in rats. WFAC significantly reduced
      the CCl4-induced increase in hepatic lipid peroxidation levels and hydroxyproline
      contents, as well as reducing the spleen weight and water content of the liver.
      WFAC also restored the hepatic soluble protein synthesis and plasma albumin
      concentration in CCl4-intoxicated rats, but it did not affect the activities of
      superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic
      morphological analysis showed that the hepatic fibrosis and necrosis induced by
      CCl4 were significantly ameliorated by WFAC. Furthermore, the body weights of
      control rats and WFAC-administered rats were not significantly different, and no
      adverse effects were observed in WFAC-administered rats. These results indicate
      that WFAC is a nontoxic hepatoprotective agent against chronic CCl4-induced
      hepatic injury. 

PMID- 27046060
TI  - Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First
      evidence for the involvement of respiratory burst enzymes in the induction of DCF
      mediated unspecific mode of action.
AB  - The present study investigates the toxic behavior of diclofenac (DCF) before and
      after its ultrasound (US) treatment, as well as the involvement of intracellular
      target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced
      adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this
      context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations
      of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating
      conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W)
      for assessing US method efficiency. In parallel, DCF and US DCF-mediated
      cytotoxic (in terms of cell viability measured with the use of neutral red
      uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric
      oxides such as NO2(-) and lipid peroxidation products, such as
      malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of
      Comet assay method) effects were investigated in hemocytes exposed for 1h to 5,
      10 and 100ngL(-1) and 1, 10 and 20MUgL(-1) of DCF. The involvement of NADPH
      oxidase and NO synthase to the DCF-induced toxicity was further investigated by
      the use of 10MUMU L-NAME, a NO synthase inhibitor and 10MUMU DPI, a NADPH oxidase
      inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher
      degradation (>50%) under 167W electric power density and frequency at 862kHz for
      120min, compared to degradation in all other cases, followed by a significant
      elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a
      significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic
      effects, which appeared to be caused by NADPH oxidase and NO synthase activation,
      since their inhibition was followed by a significant elimination of (.)O2(-) and
      NO2(-) generation and the concomitant oxidative damage within cells. The results
      of the present study showed for the first time that unspecific mode of action of
      DCF, associated with the induction of NADPH oxidase and NO synthase in mussel
      hemocytes, could be significantly diminished after partial US degradation of DCF,
      at least under optimized operating conditions currently tested. 

PMID- 27046061
TI  - School Breakfast Receipt and Obesity among American Fifth- and Eighth-Graders.
AB  - BACKGROUND: School breakfast consumption can improve children's nutrition, but
      the implications of breakfast at school for children's weight remains unclear.
      OBJECTIVE: The aim of this study was to determine whether receiving breakfast at
      school is related to changes in children's weight between the fifth and eighth
      grades, and whether the relationship between school breakfasts and obesity varies
      for children of different socioeconomic backgrounds. DESIGN: This was a
      longitudinal study of children observed in the fifth and eighth grades.
      PARTICIPANTS: Data are from the Early Childhood Longitudinal Study, Kindergarten
      Class of 1998-99, a nationally representative prospective cohort of children in
      the United States. The analytic sample consisted of 6,495 children interviewed in
      the fifth and eighth grades. MAIN OUTCOME MEASURE: Standard thresholds from the
      Centers for Disease Control and Prevention were used to classify children as not
      obese or obese based on direct-measured height and weight. STATISTICAL ANALYSES
      PERFORMED: Difference-in-difference propensity score matching and fixed-effect
      logistic regression models were used to estimate the relationship between receipt
      of school breakfast and change in obesity between the fifth and eighth grades,
      adjusting for child, household, and school characteristics. RESULTS: School
      breakfast receipt was not associated with a change in obesity status between the
      fifth and eighth grades for children overall (odds ratio=1.31; P=0.129). In the
      propensity score model, receiving school breakfasts more than doubled the odds of
      becoming obese (odds ratio=2.31; P=0.0108) for children from families below the
      federal poverty line compared with children of similar socioeconomic backgrounds
      who did not regularly receive school breakfasts. CONCLUSIONS: School breakfast
      receipt was not independently related to obesity for most children. Receiving
      school breakfasts in the fifth grade may be associated with weight gain between
      the fifth and eighth grades for children from families below the federal poverty
      line compared with children of similar socioeconomic status who did not receive
      breakfasts.

PMID- 27046062
TI  - Polymerase Acidic Protein-Basic Protein 1 (PA-PB1) Protein-Protein Interaction as
      a Target for Next-Generation Anti-influenza Therapeutics.
AB  - The limited therapeutic options against the influenza virus (flu) and increasing
      challenges in drug resistance make the search for next-generation agents
      imperative. In this context, heterotrimeric viral PA/PB1/PB2 RNA-dependent RNA
      polymerase is an attractive target for a challenging but strategic protein
      protein interaction (PPI) inhibition approach. Since 2012, the inhibition of the
      polymerase PA-PB1 subunit interface has become an active field of research
      following the publication of PA-PB1 crystal structures. In this Perspective, we
      briefly discuss the validity of flu polymerase as a drug target and its
      inhibition through a PPI inhibition strategy, including a comprehensive analysis
      of available PA-PB1 structures. An overview of all of the reported PA-PB1 complex
      formation inhibitors is provided, and approaches used for identification of the
      inhibitors, the hit-to-lead studies, and the emerged structure-activity
      relationship are described. In addition to highlighting the strengths and
      weaknesses of all of the PA-PB1 heterodimerization inhibitors, we analyze their
      hypothesized binding modes and alignment with a pharmacophore model that we have
      developed.

PMID- 27046063
TI  - Size-Shifting Micelle Nanoclusters Based on a Cross-Linked and pH-Sensitive
      Framework for Enhanced Tumor Targeting and Deep Penetration Features.
AB  - The antitumor effect of chemotherapeutics loaded micelles mainly depends on two
      aspects: the accumulation in the tumor region and the penetration into the tumor
      interior. These two processes have different demands on particle size. The
      optimal particle size for enhanced permeability and retention (EPR) is commonly
      believed to be around 100 nm, while much smaller size is desired for deeper
      penetration into the tumor interior. To address these two different requirements,
      we constructed size-shifting micelle nanoclusters (MNC) based on a cross-linked
      framework interspersed with micelles. The particle size of the micelles was 14.6
      +/- 0.8 nm and increased to 104.2 +/- 8.1 nm after the MNC were formed, leading
      to an effective utilization of the EPR effect. MNC were shifted to independent
      micelles in lysosomes, so that a more favorable particle size for penetration
      could be realized. The results of antitumor growth in vivo demonstrated that size
      shifting MNC were more beneficial for tumor therapy than micelles.

PMID- 27046064
TI  - An iron-based thin film as a highly efficient catalyst for electrochemical water
      oxidation in a carbonate electrolyte.
AB  - A highly active iron-based water-oxidation catalyst was electrodeposited from a
      CO2 saturated bicarbonate solution containing Fe(2+). This catalyst (Fe-Ci)
      produces a current density of 10 mA cm(-2) at an overpotential of 560 mV and the
      activity remains constant over 18 h in the environmentally benign HCO3(-)/CO3(2-)
      buffer (pH 9.75). A Tafel slope of 34 mV dec(-1) was obtained for Fe-Ci, which is
      lower than other reported values for iron-based catalysts. 

PMID- 27046065
TI  - Biotechnological production of fucosylated human milk oligosaccharides:
      Prokaryotic fucosyltransferases and their use in biocatalytic cascades or whole
      cell conversion systems.
AB  - Human milk oligosaccharides (HMOs) constitute a class of complex carbohydrates
      unique to mother's milk and are strongly correlated to the health benefits of
      breastfeeding in infants. HMOs are important as functional ingredients of
      advanced infant formula and have attracted broad interest for use in health
      related human nutrition. About 50% of the HMOs structures contain l-fucosyl
      residues, which are introduced into nascent oligosaccharides by enzymatic
      transfer from GDP-l-fucose. To overcome limitation in the current availability of
      fucosylated HMOs, biotechnological approaches for their production have been
      developed. Functional expression of the fucosyltransferase(s) and effective
      supply of GDP-l-fucose, respectively, are both bottlenecks of the biocatalytic
      routes of synthesis. Strategies of in vitro and in vivo production of fucosylated
      HMOs are reviewed here. Besides metabolic engineering for enhanced HMO production
      in whole cells, the focus is on the characteristics and the heterologous
      overexpression of prokaryotic alpha1,2- and alpha1,3/4-fucosyltransferases. Up to
      20g/L of fucosylated HMOs were obtained in optimized production systems.
      Optimized expression enabled recovery of purified fucosyltransferases in a yield
      of up to 45mg/L culture for alpha1,2-fucosyltransferases and of up to 200mg
      protein/L culture for alpha1,3/4-fucosyltransferases. 

PMID- 27046066
TI  - Process optimization and kinetic modelling of cyclic (1->3, 1->6)-beta-glucans
      production from Bradyrhizobium japonicum MTCC120.
AB  - Cyclic (1->3, 1->6)-beta-glucans are water soluble, biocompatible polymers with
      potential applications in food and pharmaceutical industries but have not yet
      been exploited due to their poor yield. In the present study statistical
      experimental design methodology was employed to improve their production. Initial
      screening indicated arabinose and peptone as best carbon and nitrogen source
      respectively, for glucan production. Arabinose and osmolyte concentrations as
      well as pH significantly contributed to the glucan production. Central composite
      design indicated a significant interaction between osmolyte concentration and pH
      on glucan production. The maximum amount of cyclic glucan produced was 6.7g/L in
      a 2.5L reactor in batch conditions. The logistic equation for cell growth and
      Luedeking-Piret equation for glucan production could satisfactorily simulate the
      batch kinetics data. Cyclic beta-glucans could efficiently encapsulate a
      hydrophobic molecule, curcumin and increase its solubility in water, thus
      indicating that these glucans have potential as drug delivery systems. 

PMID- 27046067
TI  - Complete genome sequence of the novel thermophilic polyhydroxyalkanoates producer
      Aneurinibacillus sp. XH2 isolated from Gudao oilfield in China.
AB  - Aneurinibacillus sp. XH2 (CGMCC 1.15535) was isolated from Gudao oilfield in
      China. It is able to use simple carbon resources to accumulate
      Polyhydroxyalkanoates (PHAs) in a thermophilic fashion. Here, we describe the
      genomic features of this strain. The total genome size of Aneurinibacillus sp.
      XH2 is 3,664,835bp and contains 3441 coding sequences and 114 tRNAs. The
      annotated genome sequence of this strain provides the genetic basis for revealing
      its role as a themophilic PHAs producing bacterium. 

PMID- 27046068
TI  - Scope, limitations and classification of lactamases.
AB  - The hydrolysis of amide bonds is a ubiquitous process in nature and is catalyzed
      by various enzymes: Whereas N-unsubstituted amides are cleaved by amidases (EC
      3.5.1.4), peptidases (EC 3.4.X.X) cleave peptide bonds in proteins and are
      involved in a number of vital physiological processes. Cyclic amides (lactams)
      are generally not hydrolyzed by proteases, but require specific lactamases. While
      the beta-lactamase family (EC 3.5.2.6), acting on highly strained beta-lactams,
      is constantly growing, lactamases able to hydrolyze gamma- and delta-lactams are
      largely under-represented, owing to the lack of ring strain of 5- and 6-membered
      cyclic amides which accounts for their lower reactivity. To date, the only known
      substrate in which a 5- or 6-membered ring lactam is enzymatically cleaved is (+/
      )-2-azabicyclo[2.2.1]hept-5-en-3-one (rac-Vince lactam), as well as four
      derivatives thereof. For these industrially relevant substrates,
      enantiocomplementary biocatalysts have been identified and their stereopreference
      was found to correlate with their amino acid sequence and protein structure:
      While (+)-lactamases belong to the amidase signature family, displaying the
      typical GGSS(S/G)GS motif in the center of the protein sequence and a conserved
      Ser-Ser-Lys catalytic triad, (-)-lactamase activity has been identified only
      among serine hydrolases, members of the alpha/beta-hydrolase fold family,
      possessing a typical Ser-His-Asp catalytic triad. For larger 8- to 13-membered
      ring lactams, few active proteins have been identified, all are members of the
      amidase signature family. An enhanced partial CN double bond character in the
      amide bond explains the lower reactivity of particularly chemically stable
      lactams. 

PMID- 27046069
TI  - Transcriptional kinetics of the cross-talk between the ortho-cleavage and TOL
      pathways of toluene biodegradation in Pseudomonas putida mt-2.
AB  - The TOL plasmid promoters are activated by toluene leading to gene expression
      responsible for the degradation of the environmental signal. Benzoate is formed
      as an intermediate, activating the BenR protein of the chromosomal ortho-cleavage
      pathway that up-regulates the chromosomal PbenA promoter and the TOL Pm promoter
      resulting in cross-talk between the two networks. Herein, the transcriptional
      kinetics of the PbenR and PbenA promoters in conjunction with TOL promoters was
      monitored by real-time PCR during toluene biodegradation of different
      concentrations in batch cultures. The cross-talk between the two pathways was
      indicated by the simultaneous maximal expression of the Pm and PbenR promoters,
      as well as the transcriptional activation from PbenA occurring prior to PbenR,
      which indicates the potential up-regulation of PbenA by the TOL XylS protein. The
      repressory effect of toluene on Pr was evident for concentrations higher than
      0.3mM suggesting a threshold value for restoring the promoter's activity, while
      all the other promoters followed a specific expression pattern, regardless of the
      initial inducer concentration. Induction of the system with higher toluene
      concentrations revealed an oscillatory behaviour of Pm, the expression of which
      remained at high levels until the late exponential phase, demonstrating a novel
      function of this network. 

PMID- 27046070
TI  - Screening for improved isoprenoid biosynthesis in microorganisms.
AB  - The production of isoprenoids in recombinant microbes for flavor & fragrance,
      pharmaceutical, agricultural or fuel applications is a booming research field.
      Isoprenoid extraction from natural resources and chemical synthesis is frequently
      neither ecological nor commercially profitable. However, recombinant microbes
      also show severe limitations in specific isoprenoid synthesis. Therefore, diverse
      directed evolution strategies have been developed for recombinant microbes. The
      focus has been laid either on the overall engineering of recombinant hosts or on
      the improvement of isoprenoid synthases. Currently, the most prominent and
      advanced approaches are based on carotenoid-producing strains, which can be
      screened by simple colorimetric readout. Other screening strategies are based on
      spectrophotometric analyses of colored by-products, fluorescence applications,
      growth selection and, to a minor extent, the use of biosensors indicating the
      pool of isoprenoid precursors. Although the number of approaches is still small,
      we observe a trend towards rigorous and highly creative assays that, however,
      often rely on the indirect detection of the evolved enzyme activities or host
      strains. We conclude that the use of whole-cellular systems is clearly favored
      over cell extracts and predict that next-generation screening assays need to be
      developed towards broader applicability and more direct assessment of isoprenoid
      production levels. 

PMID- 27046071
TI  - Centrosomal clustering contributes to chromosomal instability and cancer.
AB  - Cells assemble mitotic spindles during each round of division to insure accurate
      segregation of their duplicated genome. In animal cells, stereotypical spindles
      have two poles, each containing one centrosome, from which microtubules are
      nucleated. By contrast, many cancer cells often contain more than two centrosomes
      and form transient multipolar spindle structures with more than two poles. In
      order to divide and produce viable progeny, the multipolar spindle intermediate
      must be reshaped into a pseudo-bipolar structure via a process called centrosomal
      clustering. Pseudo-bipolar spindles appear to function normally during mitosis,
      but they occasionally give rise to aneuploid and transformed daughter cells.
      Agents that inhibit centrosomal clustering might therefore work as a potential
      cancer therapy, specifically targeting mitosis in supernumerary centrosome
      containing cells.

PMID- 27046072
TI  - Pediatric cardiovascular grafts: historical perspective and future directions.
AB  - Tissue-engineered cardiovascular patches, cardiac valves, and great vessels are
      emerging solutions for the surgical treatment of congenital cardiovascular
      abnormalities due to their potential for adapting with the growing child. The
      ideal pediatric cardiovascular patch/graft is non-thrombogenic, phenotypically
      compatible, and matches the compliance and mechanical strength of the native
      tissue, both initially and throughout growth. Bottom-up tissue engineering
      approaches, in which three-dimensional tissue is built layer-by-layer from
      scaffold-less cell sheets in vitro, offer an exciting potential solution. Cell
      source variability, sheet patterning, and scaffold-less fabrication are promising
      advantages offered by this approach. Here we review the latest developments and
      next steps in bottom-up tissue engineering targeted at meeting the necessary
      design criteria for successful pediatric cardiac tissue-engineered grafts.

PMID- 27046073
TI  - Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease: Prevalence and
      Association with PKD2 Gene Mutations.
AB  - Purpose To define the magnetic resonance (MR) imaging prevalence of pancreatic
      cysts in a cohort of patients with autosomal dominant polycystic kidney disease
      (ADPKD) compared with a control group without ADPKD that was matched for age,
      sex, and renal function. Materials and Methods In this HIPAA-compliant,
      institutional review board-approved study, all patients with ADPKD provided
      informed consent; for control subjects, informed consent was waived. Patients
      with ADPKD (n = 110) with mutations identified in PKD1 or PKD2 and control
      subjects without ADPKD or known pancreatic disease (n = 110) who were matched for
      age, sex, estimated glomerular filtration rate, and date of MR imaging
      examination were evaluated for pancreatic cysts by using axial and coronal single
      shot fast spin-echo T2-weighted images obtained at 1.5 T. Total kidney volume and
      liver volume were measured. Univariate and multivariable logistic regression
      analyses were conducted to evaluate potential associations between collected
      variables and presence of pancreatic cysts among patients with ADPKD. The number,
      size, location, and imaging characteristics of the cysts were recorded. Results
      Patients with ADPKD were significantly more likely than control subjects to have
      at least one pancreatic cyst (40 of 110 patients [36%] vs 25 of 110 control
      subjects [23%]; P = .027). In a univariate analysis, pancreatic cysts were more
      prevalent in patients with ADPKD with mutations in PKD2 than in PKD1 (21 of 34
      patients [62%] vs 19 of 76 patients [25%]; P = .0002). In a multivariable
      logistic regression model, PKD2 mutation locus was significantly associated with
      the presence of pancreatic cysts (P = .0004) and with liver volume (P = .038).
      Patients with ADPKD and a pancreatic cyst were 5.9 times more likely to have a
      PKD2 mutation than a PKD1 mutation after adjusting for age, race, sex, estimated
      glomerular filtration rate, liver volume, and total kidney volume. Conclusion
      Pancreatic cysts were more prevalent in patients with ADPKD with PKD2 mutation
      than in control subjects or patients with PKD1 mutation. ((c)) RSNA, 2016 Online
      supplemental material is available for this article.

PMID- 27046074
TI  - Early-Stage Non-Small Cell Lung Cancer: Quantitative Imaging Characteristics of
      (18)F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis.
AB  - Purpose To identify quantitative imaging biomarkers at fluorine 18 ((18)F)
      positron emission tomography (PET) for predicting distant metastasis in patients
      with early-stage non-small cell lung cancer (NSCLC). Materials and Methods In
      this institutional review board-approved HIPAA-compliant retrospective study, the
      pretreatment (18)F fluorodeoxyglucose PET images in 101 patients treated with
      stereotactic ablative radiation therapy from 2005 to 2013 were analyzed. Data for
      70 patients who were treated before 2011 were used for discovery purposes, while
      data from the remaining 31 patients were used for independent validation.
      Quantitative PET imaging characteristics including statistical, histogram
      related, morphologic, and texture features were analyzed, from which 35
      nonredundant and robust features were further evaluated. Cox proportional hazards
      regression model coupled with the least absolute shrinkage and selection operator
      was used to predict distant metastasis. Whether histologic type provided
      complementary value to imaging by combining both in a single prognostic model was
      also assessed. Results The optimal prognostic model included two image features
      that allowed quantification of intratumor heterogeneity and peak standardized
      uptake value. In the independent validation cohort, this model showed a
      concordance index of 0.71, which was higher than those of the maximum
      standardized uptake value and tumor volume, with concordance indexes of 0.67 and
      0.64, respectively. The prognostic model also allowed separation of groups with
      low and high risk for developing distant metastasis (hazard ratio, 4.8; P =
      .0498, log-rank test), which compared favorably with maximum standardized uptake
      value and tumor volume (hazard ratio, 1.5 and 2.0, respectively; P = .73 and
      0.54, log-rank test, respectively). When combined with histologic types, the
      prognostic power was further improved (hazard ratio, 6.9; P = .0289, log-rank
      test; and concordance index, 0.80). Conclusion PET imaging characteristics
      associated with distant metastasis that could potentially help practitioners to
      tailor appropriate therapy for individual patients with early-stage NSCLC were
      identified. ((c)) RSNA, 2016 Online supplemental material is available for this
      article.

PMID- 27046075
TI  - Dengue tropism for macrophages and dendritic cells: the host cell effect.
AB  - Dengue virus infects immune cells, including monocytes, macrophages and dendritic
      cells (DC). We compared virus infectivity in macrophages and DC, and found that
      the virus origin determined the cell tropism of progeny virus. The highest
      efficiency of re-infection was seen for macrophage-derived dengue virus.
      Furthermore, in the presence of enhancing antibodies, macrophage-derived virus
      gave greater enhancement of infection compared with immature DC-derived virus.
      Taken together, our results highlight the importance of macrophages in dengue
      infection.

PMID- 27046076
TI  - A multiplexed light-matter interface for fibre-based quantum networks.
AB  - Processing and distributing quantum information using photons through fibre-optic
      or free-space links are essential for building future quantum networks. The
      scalability needed for such networks can be achieved by employing photonic
      quantum states that are multiplexed into time and/or frequency, and light-matter
      interfaces that are able to store and process such states with large time
      bandwidth product and multimode capacities. Despite important progress in
      developing such devices, the demonstration of these capabilities using non
      classical light remains challenging. Here, employing the atomic frequency comb
      quantum memory protocol in a cryogenically cooled erbium-doped optical fibre, we
      report the quantum storage of heralded single photons at a telecom-wavelength
      (1.53 MUm) with a time-bandwidth product approaching 800. Furthermore, we
      demonstrate frequency-multimode storage and memory-based spectral-temporal photon
      manipulation. Notably, our demonstrations rely on fully integrated quantum
      technologies operating at telecommunication wavelengths. With improved storage
      efficiency, our light-matter interface may become a useful tool in future quantum
      networks. 

PMID- 27046077
TI  - Discovery of a small-molecule binder of the oncoprotein gankyrin that modulates
      gankyrin activity in the cell.
AB  - Gankyrin is an ankyrin-repeat oncoprotein whose overexpression has been
      implicated in the development of many cancer types. Elevated gankyrin levels are
      linked to aberrant cellular events including enhanced degradation of tumour
      suppressor protein p53, and inhibition of gankyrin activity has therefore been
      identified as an attractive anticancer strategy. Gankyrin interacts with several
      partner proteins, and a number of these protein-protein interactions (PPIs) are
      of relevance to cancer. Thus, molecules that bind the PPI interface of gankyrin
      and interrupt these interactions are of considerable interest. Herein, we report
      the discovery of a small molecule termed cjoc42 that is capable of binding to
      gankyrin. Cell-based experiments demonstrate that cjoc42 can inhibit gankyrin
      activity in a dose-dependent manner: cjoc42 prevents the decrease in p53 protein
      levels normally associated with high amounts of gankyrin, and it restores p53
      dependent transcription and sensitivity to DNA damage. The results represent the
      first evidence that gankyrin is a "druggable" target with small molecules. 

PMID- 27046078
TI  - Tracking of toddler fruit and vegetable preferences to intake and adiposity later
      in childhood.
AB  - This study examined whether toddlers' liking for fruit and vegetables (FV)
      predicts intake of FV later in childhood, how both relate to childhood adiposity
      and how these were moderated by factors in infancy. Children in the Gateshead
      Millennium Study were recruited at birth in 1999-2000. Feeding data collected in
      the first year were linked to data from a parental questionnaire completed for
      456 children at age 2.5 years (30 m) and to anthropometry, skinfolds and
      bioelectrical impedance and 4-day food diary data collected for 293 of these
      children at age 7 years. Aged 30 months, 50% of children were reported to like
      eight different vegetables and three fruits, but at 7 years, children ate a
      median of only 1.3 (range 0-7) portions of vegetables and 1.0 portion of fruit (0
      4). Early appetite, feeding problems and food neophobia showed significant
      univariate associations with liking for FV aged 30 m, but the number of
      vegetables toddlers liked was the only independent predictor of vegetable
      consumption at age 7 years (odds ratio (OR) 1.28 p < 0.001). Liking for fruit
      aged 30 m also independently predicted fruit intake (OR = 1.31, p = 0.016), but
      these were also related to deprivation (OR = 2.69, p = 0.001) maternal education
      (OR = 1.28, p = 0.039) and female gender (OR = 1.8, p = 0.024). Children eating
      more FV at age 7 years had slightly lower body mass index and skinfolds. An early
      liking for FV predicted increased later intake, so increasing early exposure to
      FV could have long term beneficial consequences.

PMID- 27046079
TI  - Computational Analysis of the Predicted Evolutionary Conservation of Human
      Phosphorylation Sites.
AB  - Protein kinase-mediated phosphorylation is among the most important post
      translational modifications. However, few phosphorylation sites have been
      experimentally identified for most species, making it difficult to determine the
      degree to which phosphorylation sites are conserved. The goal of this study was
      to use computational methods to characterize the conservation of human
      phosphorylation sites in a wide variety of eukaryotes. Using experimentally
      determined human sites as input, homologous phosphorylation sites were predicted
      in all 432 eukaryotes for which complete proteomes were available. For each pair
      of species, we calculated phosphorylation site conservation as the number of
      phosphorylation sites found in both species divided by the number found in at
      least one of the two species. A clustering of the species based on this
      conservation measure was concordant with phylogenies based on traditional genomic
      measures. For a subset of the 432 species, phosphorylation site conservation was
      compared to conservation of both protein kinases and proteins in general. Protein
      kinases exhibited the highest degree of conservation, while general proteins were
      less conserved and phosphorylation sites were least conserved. Although
      preliminary, these data tentatively suggest that variation in phosphorylation
      sites may play a larger role in explaining phenotypic differences among organisms
      than differences in the complements of protein kinases or general proteins. 

PMID- 27046080
TI  - Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF
      Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.
AB  - NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling
      complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes,
      NURF is able to alter chromatin dynamics to control transcription and genome
      organization. Previous biochemical and genetic analysis of the specificity
      subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx)) has defined NURF
      as a critical regulator of homeotic, heat-shock and steroid-responsive gene
      transcription. It has been speculated that NURF controls pathway specific
      transcription by co-operating with sequence-specific transcription factors to
      remodel chromatin at dedicated enhancers. However, conclusive in vivo
      demonstration of this is lacking and precise regulatory elements targeted by NURF
      are poorly defined. To address this, we have generated a comprehensive map of in
      vivo NURF activity, using MNase-sequencing to determine at base pair resolution
      NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment.
      Our data show that, besides anticipated roles at enhancers, NURF interacts
      physically and functionally with the TRF2/DREF basal transcription factor to
      organize nucleosomes downstream of active promoters. Moreover, we detect NURF
      remodeling and recruitment at distal insulator sites, where NURF functionally
      interacts with and co-localizes with DREF and insulator proteins including CP190
      to establish nucleosome-depleted domains. This insulator function of NURF is most
      apparent at subclasses of insulators that mark the boundaries of chromatin
      domains, where multiple insulator proteins co-associate. By visualizing the
      complete repertoire of in vivo NURF chromatin targets, our data provide new
      insights into how chromatin remodeling can control genome organization and
      regulatory interactions. 

PMID- 27046081
TI  - CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity
      associated cancer.
AB  - Obesity is a global health problem presenting serious risk of disease fuelled by
      chronic inflammation, including type 2 diabetes mellitus, cardiovascular disease,
      liver disease and cancer. Visceral fat, in particular the omentum and liver of
      obese individuals are sites of excessive inflammation. We propose that chemokine
      mediated trafficking of pro-inflammatory cells to the omentum and liver
      contributes to local and subsequent systemic inflammation. Oesophagogastric
      adenocarcinoma (OAC) is an exemplar model of obesity and inflammation driven
      cancer. We have demonstrated that T cells actively migrate to the secreted
      factors from the omentum and liver of OAC patients and that both CD4(+) and
      CD8(+) T cells bearing the chemokine receptor CCR5 are significantly more
      prevalent in these tissues compared to matched blood. The CCR5 ligand and
      inflammatory chemokine MIP-1alpha is also secreted at significantly higher
      concentrations in the omentum and liver of our OAC patient cohort compared to
      matched serum. Furthermore, we report that MIP-1alpha receptor antagonism can
      significantly reduce T cell migration to the secreted factors from OAC omentum
      and liver. These novel data suggest that chemokine receptor antagonism may have
      therapeutic potential to reduce inflammatory T cell infiltration to the omentum
      and liver and in doing so, may ameliorate pathological inflammation in obesity
      and obesity-associated cancer.

PMID- 27046082
TI  - TCR transgenic mice reveal the impact of type 1 diabetes loci on early and late
      disease checkpoints.
AB  - Linkage analysis studies for autoimmune diabetes have revealed multiple non-major
      histocompatibility complex (MHC) chromosomal regions linked to disease
      susceptibility. To date, more than 20 insulin-dependent diabetes (Idd) loci
      linked to diabetes susceptibility have been identified in NOD mice and validated
      via congenic breeding. Importantly, evidence suggests that Idd loci may regulate
      at least two pathological steps during autoimmune diabetes development, namely
      the onset of insulitis and the transition from insulitis to overt diabetes. Here
      we assess the role of various non-MHC Idd diabetes-resistance loci, which have
      been validated in the non-transgenic setting, on autoimmune diabetes progression
      in the transgenic setting. Specifically, we generated multiple Idd congenic
      strains in the 3A9-TCR:insHEL NOD.H2(k) transgenic model and monitored their
      diabetes incidence. We show that 3A9-TCR:insHEL NOD.H2(k) mice congenic for Idd3
      or Idd5 display a reduction in diabetes development, whereas mice congenic for
      Idd9 or Idd13 exhibit an increase, in comparison with 3A9-TCR:insHEL NOD.H2(k)
      mice. These results suggest that the presence of the 3A9-TCR and hen egg lysosyme
      transgenes can offset the regulatory function of certain diabetes-resistance
      genetic variants contained within the Idd loci, including Idd9 and Idd13. We
      propose the antigen-specific 3A9-TCR:insHEL transgenic model as a useful tool for
      the study of the genetics of autoimmune diabetes development.

PMID- 27046083
TI  - Prion Strain Differences in Accumulation of PrPSc on Neurons and Glia Are
      Associated with Similar Expression Profiles of Neuroinflammatory Genes:
      Comparison of Three Prion Strains.
AB  - Misfolding and aggregation of host proteins are important features of the
      pathogenesis of neurodegenerative diseases including Alzheimer's disease,
      Parkinson's disease, frontotemporal dementia and prion diseases. In all these
      diseases, the misfolded protein increases in amount by a mechanism involving
      seeded polymerization. In prion diseases, host prion protein is misfolded to form
      a pathogenic protease-resistant form, PrPSc, which accumulates in neurons,
      astroglia and microglia in the CNS. Here using dual-staining
      immunohistochemistry, we compared the cell specificity of PrPSc accumulation at
      early preclinical times post-infection using three mouse scrapie strains that
      differ in brain regional pathology. PrPSc from each strain had a different
      pattern of cell specificity. Strain 22L was mainly associated with astroglia,
      whereas strain ME7 was mainly associated with neurons and neuropil. In thalamus
      and cortex, strain RML was similar to 22L, but in substantia nigra, RML was
      similar to ME7. Expression of 90 genes involved in neuroinflammation was studied
      quantitatively using mRNA from thalamus at preclinical times. Surprisingly,
      despite the cellular differences in PrPSc accumulation, the pattern of
      upregulated genes was similar for all three strains, and the small differences
      observed correlated with variations in the early disease tempo. Gene upregulation
      correlated with activation of both astroglia and microglia detected in early
      disease prior to vacuolar pathology or clinical signs. Interestingly, the profile
      of upregulated genes in scrapie differed markedly from that seen in two acute
      viral CNS diseases (LaCrosse virus and BE polytropic Friend retrovirus) that had
      reactive gliosis at levels similar to our prion-infected mice. 

PMID- 27046084
TI  - Recombinant Human Plasminogen Activator Inhibitor-1 Accelerates Odontoblastic
      Differentiation of Human Stem Cells from Apical Papilla.
AB  - Dental caries, the most prevalent oral disease in dental patients, involves the
      phases of demineralization and destruction of tooth hard tissues like enamel,
      dentin, and cementum. Dentin is a major component of the root and is also the
      innermost layer that protects the tooth nerve, exposure of which results in pain.
      In this study, we used human stem cells from apical papilla (hSCAP), which are
      early progenitor cells, to examine the effects of recombinant human plasminogen
      activator inhibitor-1 (rhPAI-1) on odontogenic differentiation in vitro and in
      vivo. We demonstrated that rhPAI-1 promoted the proliferation and odontogenic
      differentiation of hSCAP and increased the expression levels of odontoblast
      associated markers. We also observed that rhPAI-1 upregulated the expression of
      Smad4, nuclear factor I-C (NFI-C), Runx2, and osterix (OSX) during odontogenic
      differentiation. Notably, transplantation of rhPAI-1-treated hSCAP effectively
      induced odontoblastic differentiation and dentinal formation. And the
      differentiated odontoblast-like cells showed numerous odontoblast processes
      inserted in dentin tubules and arranged collagen fibers. Furthermore, odontoblast
      associated markers were more highly expressed in the rhPAI-1-induced
      differentiated odontoblast-like cells compared with the control group. These
      markers were also more highly expressed in the newly formed dentin-like tissue of
      the rhPAI-1-treated group compared with the control group. Consistent with our in
      vitro results, the expression levels of Smad4, NFI-C, and OSX were also increased
      in the rhPAI-1-treated group compared with the control group. Taken together,
      these results suggest that rhPAI-1 promotes odontoblast differentiation and
      dentin formation of hSCAP, and Smad4/NFI-C/OSX may play critical roles in the
      rhPAI-1-induced odontogenic differentiation. Thus, dental stem cells from apical
      papilla combined with rhPAI-1 could lead to dentin regeneration in clinical
      implications.

PMID- 27046085
TI  - Development of Novel Criteria of the "Lethal Triad" as an Indicator of Decision
      Making in Current Trauma Care: A Retrospective Multicenter Observational Study in
      Japan.
AB  - OBJECTIVES: To evaluate the utility of the conventional lethal triad in current
      trauma care practice and to develop novel criteria as indicators of treatment
      strategy. DESIGN: Retrospective observational study. SETTINGS: Fifteen acute
      critical care medical centers in Japan. PATIENTS: In total, 796 consecutive
      trauma patients who were admitted to emergency departments with an injury
      severity score of greater than or equal to 16 from January 2012 to December 2012.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data were retrospectively
      collected, including laboratory data on arrival. Sensitivities to predict trauma
      death within 28 days of prothrombin time international normalized ratio greater
      than 1.50, pH less than 7.2, and body temperature less than 35 degrees C were
      15.7%, 17.5%, and 15.9%, respectively, and corresponding specificities of these
      were 96.4%, 96.6%, and 93.6%, respectively. The best predictors associated with
      hemostatic disorder and acidosis were fibrin/fibrinogen degradation product and
      base excess (the cutoff values were 88.8 ug/mL and -3.05 mmol/L). The optimal
      cutoff value of hypothermia was 36.0 degrees C. The impact of the
      fibrin/fibrinogen degradation product and base excess abnormality on the outcome
      were approximately three- and two-folds compared with those of hypothermia. Using
      these variables, if the patient had a hemostatic disorder alone or a combined
      disorder with acidosis and hypothermia, the sensitivity and specificity were
      80.7% and 66.8%. CONCLUSIONS: Because of the low sensitivity and high
      specificity, conventional criteria were unsuitable as prognostic indicators. Our
      revised criteria are assumed to be useful for predicting trauma death and have
      the potential to be the objective indicators for activating the damage control
      strategy in early trauma care.

PMID- 27046086
TI  - Liberal Versus Conventional Glucose Targets in Critically Ill Diabetic Patients:
      An Exploratory Safety Cohort Assessment.
AB  - OBJECTIVES: To assess the feasibility, safety, and impact on relative
      hypoglycemia of liberal versus conventional blood glucose concentration targets
      in critically ill diabetic patients. DESIGN: Prospective, open-label, sequential
      period exploratory study. SETTING: A 22-bed multidisciplinary ICU of a tertiary
      care hospital in Australia. PATIENTS: Eighty adult diabetic patients, 40 from the
      conventional before period and 40 from the liberal after period. INTERVENTIONS:
      Blood glucose concentration targets were 6-10 mmol/L during the before period and
      10-14 mmol/L during the after period. MEASUREMENTS AND MAIN RESULTS: We used
      admission glycated hemoglobin to estimate premorbid baseline blood glucose
      concentration. We defined glycemic distance as the difference between blood
      glucose concentration in ICU and baseline blood glucose concentration. During the
      first 48 ICU hours, we recorded absolute (blood glucose concentration, < 3.9
      mmol/L) and relative (glycemic distance, > 30% below baseline) hypoglycemia
      rates, insulin administration, and outcomes. The groups had similar baseline
      characteristics. We observed a negative glycemic distance in 248 of 488 blood
      glucose concentrations (50.8%) during the before period and 164 of 485 (33.8%)
      during the after period (p < 0.001). We detected relative hypoglycemia in 20
      (50.0%) and nine (22.5%) patients in the before and after periods, respectively
      (p = 0.01). On day 1, 50.0% and 16.7% received insulin in the before and after
      periods (p = 0.007). ICU and hospital length of stay and mortality were similar
      between groups. CONCLUSIONS: In a safety cohort of critically ill diabetic
      patients, a blood glucose concentration target of 10-14 mmol/L resulted in fewer
      episodes of negative glycemic distance or relative hypoglycemia and reduced
      insulin administration compared with a target of 6-10 mmol/L.

PMID- 27046087
TI  - Increased density and periosteal expansion of the tibia in young adult men
      following short-term arduous training.
AB  - PURPOSE: Few human studies have reported early structural adaptations of bone to
      weight-bearing exercise, which provide a greater contribution to improved bone
      strength than increased density. This prospective study examined site- and
      regional-specific adaptations of the tibia during arduous training in a cohort of
      male military (infantry) recruits to better understand how bone responds in vivo
      to mechanical loading. METHODS: Tibial bone density and geometry were measured in
      90 British Army male recruits (ages 21+/-3years, height: 1.78+/-0.06m, body mass:
      73.9+/-9.8kg) in weeks 1 (Baseline) and 10 of initial military training. Scans
      were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end
      plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software
      (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional
      sectors. T-tests determined significant differences between time points (P<0.05).
      RESULTS: Bone density of trabecular and cortical compartments increased
      significantly at all measured sites. Bone geometry (cortical area and thickness)
      and bone strength (i, MMi and BSI) at the diaphyseal sites (38 and 66%) were also
      significantly higher in week 10. Regional changes in density and geometry were
      largely observed in the anterior, medial-anterior and anterior-posterior sectors.
      Calf muscle density and area (66% site) increased significantly at week 10
      (P<0.01). CONCLUSIONS: In vivo mechanical loading improves bone strength of the
      human tibia by increased density and periosteal expansion, which varies by site
      and region of the bone. These changes may occur in response to the nature and
      distribution of forces originating from bending, torsional and shear stresses of
      military training. These improvements are observed early in training when the
      osteogenic stimulus is sufficient, which may be close to the fracture threshold
      in some individuals.

PMID- 27046088
TI  - Effect of different synthetic membranes on laboratory parameters and survival in
      chronic haemodialysis patients.
AB  - Background. A number of studies suggested that the type of dialysis membrane is
      associated with differences in long-term outcome of patients undergoing
      haemodialysis, both in terms of morbidity and mortality. In the majority of
      dialysis units, synthetic membranes are being used. However, no studies are
      available so far for comparison between different biocompatible membranes.
      Therefore, we studied the influence of high- and low-flux polysulphone membranes
      (PS) in comparison with polymethylmethacrylate (PMMA) membranes on mortality and
      morbidity on the basis of various laboratory parameters. Methods. In a cohort
      study, data of 260 consecutive haemodialysis patients entering our dialysis unit
      in the years 2003-07 were collected, comparing 435 PS patient-years and 85 PMMA
      patient-years. PMMA membranes (n = 33) were used for those patients who did not
      tolerate (e.g. for pruritus) PS membranes (n = 227). Low-flux dialysers (n = 233)
      were compared with high-flux (n = 37). Laboratory values were evaluated by
      unpaired t-test, and mortality was evaluated by log-rank test and Cox regression
      analysis adjusted for age, diabetes and laboratory parameters. Results. Patients
      in our dialysis unit had a high cardiovascular risk as demonstrated by a
      proportion of 63% of peripheral arterial disease. Despite this, cumulative
      survival was almost 60% after 5 years on dialysis. It was slightly but not
      significantly higher in patients on PMMA (68%) compared with PS dialysers (54%)
      and on high-flux (61%) versus low-flux membranes (54%). After accounting for the
      confounding effect of age and diabetes in the multivariate Cox regression
      analysis, there was no impact of the membranes used (high- or low-flux, PMMA or
      PS) on survival. Only age at the onset of dialysis showed a significant influence
      on survival (P <= 0.001). Independent predictors of mortality in all patients in
      the multivariate Cox regression analysis were age, haemoglobin, leucocytes, C
      reactive protein (CRP) and creatinine. Laboratory parameters between the high-
      and low- flux groups were not different. PS-treated patients showed significantly
      (P <= 0.05) higher values for leucocytes, thrombocytes, ferritin, and CRP and
      lower values for haemoglobin, transferrin, creatinine, uric acid, creatine kinase
      (CK), and sodium than PMMA-treated patients. Irrespective of the membrane used,
      in deceased patients, the following laboratory values were higher than for
      patients alive: leucocytes, thrombocytes, ferritin and CRP; the following were
      lower: haemoglobin, iron, total protein, urea, creatinine, uric acid and CK.
      Conclusions. The data of 260 severely ill haemodialysis patients showed a
      slightly, but not significantly, reduced mortality in patients treated with PMMA
      membranes in comparison with PS and with high-flux membranes compared with low
      flux. High- or low-flux membranes exhibited no difference in laboratory values.
      However, in PMMA patients, laboratory data with respect to inflammation, anaemia
      and nutrition were significantly improved compared with the PS group. A similarly
      positive laboratory pattern was seen in patients alive compared with patients
      deceased with both membrane types. The favourable effect of PMMA membranes may be
      explained by the reduced activation of catabolic components and inflammation,
      which, in turn, would result in an improved nutrition and better response to
      recombinant human erythropoietin.

PMID- 27046089
TI  - Clustering mechanism of ethanol-water mixtures investigated with photothermal
      microfluidic cantilever deflection spectroscopy.
AB  - The infrared-active (IR) vibrational mode of ethanol (EtOH) associated with the
      asymmetrical stretching of the C-C-O bond in pico-liter volumes of EtOH-water
      binary mixtures is calorimetrically measured using photothermal microfluidic
      cantilever deflection spectroscopy (PMCDS). IR absorption by the confined liquid
      results in wavelength dependent cantilever deflections, thus providing a
      complementary response to IR absorption revealing a complex dipole moment
      dependence on mixture concentration. Solvent-induced blue shifts of the C-C-O
      asymmetric vibrational stretch for both anti and gauche conformers of EtOH were
      precisely monitored for EtOH concentrations ranging from 20-100% w/w. Variations
      in IR absorption peak maxima show an inverse dependence on induced EtOH dipole
      moment (MU) and is attributed to the complex clustering mechanism of EtOH-water
      mixtures. 

PMID- 27046090
TI  - Hypersensitivity to Cold Stimuli in Symptomatic Contact Lens Wearers.
AB  - PURPOSE: To examine the cooling thresholds and the estimated sensation magnitude
      at stimulus detection in controls and symptomatic and asymptomatic contact lens
      (CL) wearers, to determine whether detection thresholds depend on the presence of
      symptoms of dryness and discomfort. METHODS: Forty-nine adapted CL wearers and 15
      non-lens wearing controls had room temperature pneumatic thresholds measured
      using a custom Belmonte esthesiometer, during Visits 1 and 2 (Baseline CL), Visit
      3 (2 weeks no CL wear), and Visit 4 (2 weeks after resuming CL wear). CL wearers
      were subdivided into symptomatic and asymptomatic groups based on comfortable
      wearing time (CWT) and CLDEQ-8 score (<8 hours CWT and >=14 CLDEQ-8 stratified
      the symptom groups). Detection thresholds were estimated using an ascending
      method of limits and each threshold was the average of the three first-reported
      flow rates. The magnitude of intensity, coolness, irritation, and pain at
      detection of the stimulus were estimated using a 1-100 scale (1 very mild, 100
      very strong). RESULTS: In all measurement conditions, the symptomatic CL wearers
      were the most sensitive, the asymptomatic CL wearers were the least sensitive,
      and the control group was between the two CL wearing groups (group factor p <
      0.001, post hoc asymptomatic vs. symptomatic group, all p's < 0.015). Similar
      patterns were found for the estimated magnitude of intensity and irritation
      (group effect p = 0.027 and 0.006 for intensity and irritation, respectively) but
      not for cooling (p > 0.05) at detection threshold. CONCLUSIONS: Symptomatic CL
      wearers have higher cold detection sensitivity and report greater intensity and
      irritation sensation at stimulus detection than the asymptomatic wearers. Room
      temperature pneumatic esthesiometry may help to better understand the process of
      sensory adaptation to CL wear.

PMID- 27046091
TI  - Prevalence of Diabetic Retinopathy in a Clinic Population from Puerto Rico.
AB  - PURPOSE: Diabetic retinopathy (DR) is a preventable or treatable cause of
      blindness in the adult population. The prevalence of diabetes mellitus (DM) in
      Puerto Ricans is the highest among Hispanics. This study evaluated the prevalence
      of DR in a screening program of DM subjects in a clinic system in Puerto Rico.
      METHODS: A retrospective cross-sectional health records study of DM patients
      referred by primary care physicians for dilated retinal evaluation to the Inter
      American University of Puerto Rico School of Optometry Juana Diaz Eye Institute
      Clinic between 2001 and 2009 was performed. All subjects underwent a complete eye
      evaluation including fundus photography. Photographs were graded following the
      Early Treatment Diabetic Retinopathy Study protocols. RESULTS: A total of 411
      randomly selected health records of DM subjects older than 30 years were
      included. The estimated prevalence of DR among all subjects is 37.7%. DR was more
      common in males (47.2%) than females (33.7%). The age range with higher frequency
      of DR is among ages 60 to 69 (34.8%) and the lowest between ages 30 and 39
      (3.9%). The average number of years since initial DM diagnosis was 12.48.
      Probability of developing DR increases with longer duration of DM (p < 0.05). The
      most common stage was mild non-proliferative DR (22.6%). CONCLUSIONS: Our data
      revealed that prevalence of DR was high among Puerto Ricans. Mild stage
      retinopathy was most prevalent and there exists an increase in probability to
      develop DR with duration of DM. The prevalence of DR in total population may be
      different than the findings presented in this paper. Comprehensive studies are
      needed to understand and estimate the progression and impact of DR in this
      population.

PMID- 27046092
TI  - Optical Characterization Method for Tilted or Decentered Intraocular Lenses.
AB  - PURPOSE: To test and validate a method for measuring the optical quality and
      optical power of monofocal intraocular lenses (IOLs) in the presence of a tilt or
      a decentration as well as its optical power. METHODS: The experimental system
      consists of an artificial eye (wet-cell) and a commercial aberrometer with a
      Shack-Hartmann sensor. Optical image quality parameters such as point spread
      function (PSF), modulation transfer function (MTF), and the simulations of the
      retinal image of an extended object are computed from the in vitro wavefront data
      of an IOL. Repeatability and reproducibility of the system are tested.
      Mathematical and ray-tracing simulations are used to ascertain the precision and
      accuracy of the method. Comparison with a standard single-pass method of
      measurement is also made. Optical properties of four commercial monofocal IOLs
      are measured under tilts of 0 degrees , 2 degrees , and 4 degrees , and vertical
      decentrations of 0, 0.2, and 0.4 mm; the results of such measurements are
      compared with a ray-tracing simulation. RESULTS: Precision and accuracy of the
      system are in good agreement with theoretical calculations. Reproducibility and
      repeatability are within standard ISO norms. MTFs obtained with this method and
      with the standard method are very similar. The precision of the estimation of the
      IOL's optical power is higher than 98.6%. Commercially tested IOLs show a
      decrease of optical quality in the presence of decentrations and tilts, and their
      susceptibility to tilts and decentrations depends on the asphericity. These
      results are in concordance with the results obtained by ray-tracing simulation.
      CONCLUSIONS: A simple wavefront-based method for in vitro measurements of the
      wavefront aberrations and power of an IOL is proposed and tested showing accurate
      and precise results.

PMID- 27046093
TI  - Directional Optical Coherence Tomography Reveals Reliable Outer Nuclear Layer
      Measurements.
AB  - PURPOSE: Directional Optical Coherence Tomography (D-OCT) is a method used to
      optically segment and identify the outer nuclear layer (ONL) in vivo. The purpose
      of this study was to determine the repeatability and reproducibility of D-OCT ONL
      thickness measurements in healthy eyes. METHODS: Sixteen healthy eyes of sixteen
      subjects were imaged using the Cirrus SD-OCT. The OCT beam entry position was
      varied horizontally and vertically through the pupil, and cross-sectional images
      were obtained at baseline and 1-month follow-up by two observers. Detailed
      segmentation was performed to quantify the thickness of ONL without the inclusion
      of overlying Henle Fiber Layer. Inter-observer, intra-observer, and inter-visit
      variability was evaluated using Bland-Altman and coefficient of variation
      analysis for each category. RESULTS: All 16 eyes were successfully imaged,
      registered, and segmented. The maximum mean (SD) inter-operator difference was
      2.6 (4.8) MUm. The maximum mean (SD) intra-operator difference was 2.4 (5.3) MUm.
      There was no statistically significant difference in ONL measurements detected
      between baseline and follow-up (p > 0.05). The mean (SD) differences measured
      across visits by one operator varied from -1.6 (3.1) to 1.1 (6.1) MUm. The mean
      (SD) coefficient of variance (CV%) for all sectors with horizontal orientation
      was 9.1% (2.3%), 10.1% (2.5%), and 8.6% (2.3%) for inter-observer, intra
      observer, and inter-visit, respectively. The mean (SD) coefficient of variance
      (CV%) for all sectors with vertical orientation was 8.3% (1.8%), 6.9% (1.4%), and
      8.3% (2.1%) for inter-observer, intra-observer, and inter-visit, respectively.
      The majority of the variation of paired repeated measurements originated from
      between-subject variance. The within-subject variance accounted for less than 1%
      of the total variability. CONCLUSIONS: ONL thickness measurements can be
      quantified with good repeatability and reproducibility using D-OCT. Identifying
      the magnitude of D-OCT variability among normal subjects will allow for improved
      development of future clinical studies that quantitatively track the progression
      of macular pathology.

PMID- 27046094
TI  - High expression of Rab3D predicts poor prognosis and associates with tumor
      progression in colorectal cancer.
AB  - Rab3D belongs to Rab protein family. Previous reports showed that the expression
      of Rab3D was dysregulated in various types of cancer. Rab3D belongsRab3D belongs.
      However, little is known about the role of Rab3D in carcinogenesis and
      progression of colorectal cancer (CRC). Here, we first evaluated the expression
      of Rab3D in 32 fresh CRC and matched normal tissues and found Rab3D was
      dramatically increased in CRC tissues compared to normal tissues (p<0.001).
      Furthermore, immunochemistry was used to investigate Rab3D expression in 300CRC
      tissue specimens. The expression of Rab3D significantly positively correlated
      with the tumor size (p=0.041), CEA level (p=0.007), tumor classification
      (p=0.030), lymphatic metastasis (p<0.001), distant metastasis (p=0.013) and
      clinical stage (p=0.003). We also demonstrated that overall survival is poor in
      CRC patients with high expression of Rab3D (p<0.001). Finally, we showed that
      Rab3D activated Akt/GSK3beta/Snail pathway and induced EMT process in colorectal
      cancer cells. In conclusion, this study establishes increased Rab3D expression is
      associated with invasiveness of CRC cells, and Rab3D expression status may serve
      as a reliable prognostic biomarker in CRC patients.

PMID- 27046095
TI  - En Route to a Practical Primary Alcohol Deoxygenation.
AB  - A long-standing scientific challenge in the field of alcohol deoxygenation has
      been direct catalytic sp(3) C-O defunctionalization with high selectivity and
      efficiency, in the presence of other functionalities, such as free hydroxyl
      groups and amines widely present in biological molecules. Previously, the
      selectivity issue had been only addressed by classic multistep deoxygenation
      strategies with stoichiometric reagents. Herein, we propose a catalytic late
      transition-metal-catalyzed redox design, on the basis of dehydrogenation/Wolff
      Kishner (WK) reduction, to simultaneously tackle the challenges regarding step
      economy and selectivity. The early development of our hypothesis focuses on an
      iridium-catalyzed process efficient mainly with activated alcohols, which
      dictates harsh reaction conditions and thus limits its synthetic utility. Later,
      a significant advancement has been made on aliphatic primary alcohol
      deoxygenation by employing a ruthenium complex, with good functional group
      tolerance and exclusive selectivity under practical reaction conditions. Its
      synthetic utility is further illustrated by excellent efficiency as well as
      complete chemo- and regio-selectivity in both simple and complex molecular
      settings. Mechanistic discussion is also included with experimental supports.
      Overall, our current method successfully addresses the aforementioned challenges
      in the pertinent field, providing a practical redox-based approach to the direct
      sp(3) C-O defunctionalization of aliphatic primary alcohols.

PMID- 27046096
TI  - Correction to: Hum Gene Ther 2016;27(1):60-71.

PMID- 27046097
TI  - Modeling meiotic chromosome pairing: nuclear envelope attachment, telomere-led
      active random motion, and anomalous diffusion.
AB  - The recognition and pairing of homologous chromosomes during meiosis is a complex
      physical and molecular process involving a combination of polymer dynamics and
      molecular recognition events. Two highly conserved features of meiotic chromosome
      behavior are the attachment of telomeres to the nuclear envelope and the active
      random motion of telomeres driven by their interaction with cytoskeletal motor
      proteins. Both of these features have been proposed to facilitate the process of
      homolog pairing, but exactly what role these features play in meiosis remains
      poorly understood. Here we investigate the roles of active motion and nuclear
      envelope tethering using a Brownian dynamics simulation in which meiotic
      chromosomes are represented by a Rouse polymer model subjected to tethering and
      active forces at the telomeres. We find that tethering telomeres to the nuclear
      envelope slows down pairing relative to the rates achieved by unattached
      chromosomes, but that randomly directed active forces applied to the telomeres
      speed up pairing dramatically in a manner that depends on the statistical
      properties of the telomere force fluctuations. The increased rate of initial
      pairing cannot be explained by stretching out of the chromosome conformation but
      instead seems to correlate with anomalous diffusion of sub-telomeric regions. 

PMID- 27046098
TI  - Rigid Organization of Fluorescence-Active Ligands by Artificial Macrocyclic
      Receptor to Achieve the Thioflavin T-Amyloid Fibril Level Association.
AB  - The push-pull molecules with an intramolecular charge transfer from donor to
      acceptor sides upon excitation exhibit a wide variety of biological and
      electronic activities, as exemplified by the in vivo fluorescence imaging probes
      for amyloid fibrils in the diagnosis and treatment of amyloid diseases.
      Interestingly, the structurally much simpler bis(4,8-disulfonato-1,5-naphtho)-32
      crown-8 (DNC), in keen contrast to the conventional macrocyclic receptors, was
      found to dramatically enhance the fluorescence of twisted intramolecular charge
      transfer molecules possessing various benzothiazolium and stilbazolium
      fluorophores upon complexation. Spectroscopic and microcalorimetric titrations
      jointly demonstrated the complex structures and the interactions that promote the
      extremely strong complexation, revealing that the binding affinity in these
      artificial host-guest pairs could reach up to a nearly 10(7) M(-1) order of
      magnitude in water, and the sandwich-type complexation is driven by
      electrostatic, hydrophobic, pi-stacking, and hydrogen-bonding interactions.
      Quantum chemical calculations on free molecules and their DNC-bound species in
      both the ground and excited states elucidated that the encapsulation by DNC could
      greatly deter the central single and double chemical bonds from free
      intramolecular rotation in the singlet excited state, thus leading to the unique
      and unprecedented fluorescence enhancement upon sandwich-type complexation. This
      complexation-induced structural reorganization mechanism may also apply to the
      binding of other small-molecule ligands by functional receptors and contribute to
      the molecular-level understanding of the receptor-ligand interactions in many
      biology-related systems.

PMID- 27046099
TI  - Biotransformation of Two Pharmaceuticals by the Ammonia-Oxidizing Archaeon
      Nitrososphaera gargensis.
AB  - The biotransformation of some micropollutants has previously been observed to be
      positively associated with ammonia oxidation activities and the transcript
      abundance of the archaeal ammonia monooxygenase gene (amoA) in nitrifying
      activated sludge. Given the increasing interest in and potential importance of
      ammonia-oxidizing archaea (AOA), we investigated the capabilities of an AOA pure
      culture, Nitrososphaera gargensis, to biotransform ten micropollutants belonging
      to three structurally similar groups (i.e., phenylureas, tertiary amides, and
      tertiary amines). N. gargensis was able to biotransform two of the tertiary
      amines, mianserin (MIA) and ranitidine (RAN), exhibiting similar compound
      specificity as two ammonia-oxidizing bacteria (AOB) strains that were tested for
      comparison. The same MIA and RAN biotransformation reactions were carried out by
      both the AOA and AOB strains. The major transformation product (TP) of MIA, alpha
      oxo MIA was likely formed via a two-step oxidation reaction. The first
      hydroxylation step is typically catalyzed by monooxygenases. Three RAN TP
      candidates were identified from nontarget analysis. Their tentative structures
      and possible biotransformation pathways were proposed. The biotransformation of
      MIA and RAN only occurred when ammonia oxidation was active, suggesting
      cometabolic transformations. Consistently, a comparative proteomic analysis
      revealed no significant differential expression of any protein-encoding gene in
      N. gargensis grown on ammonium with MIA or RAN compared with standard cultivation
      on ammonium only. Taken together, this study provides first important insights
      regarding the roles played by AOA in micropollutant biotransformation.

PMID- 27046100
TI  - Segmentation of the left ventricular endocardium from magnetic resonance images
      by using different statistical shape models.
AB  - We evaluate in this paper different strategies for the construction of a
      statistical shape model (SSM) of the left ventricle (LV) to be used for
      segmentation in cardiac magnetic resonance (CMR) images. From a large database of
      LV surfaces obtained throughout the cardiac cycle from 3D echocardiographic (3DE)
      LV images, different LV shape models were built by varying the considered phase
      in the cardiac cycle and the registration procedure employed for surface
      alignment. Principal component analysis was computed to describe the statistical
      variability of the SSMs, which were then deformed by applying an active shape
      model (ASM) approach to segment the LV endocardium in CMR images of 45 patients.
      Segmentation performance was evaluated by comparing LV volumes derived by ASM
      segmentation with different SSMs and those obtained by manual tracing, considered
      as a reference. A high correlation (r(2)>0.92) was found in all cases, with
      better results when using the SSM models comprising more than one frame of the
      cardiac cycle.

PMID- 27046101
TI  - A rare case report of Solid Pseudopapillary Tumor of the pancreas with portal
      hypertension.
AB  - INTRODUCTION: Solid Pseudopapillary Tumor of the pancreas (SPT) is a rare
      pancreatic tumor and represents 1-3% of all pancreatic tumors. It usually
      presents in young females with abdominal pain, nausea, vomiting and abdominal
      fullness. The first case report was documented in 1959 and since then multiple
      case reports have been documented on the various surgical approaches for SPT.
      However, there are not many reported cases where surgery has been performed on
      SPT with portal hypertension. PRESENTATION OF CASE: In our case report, a 19 year
      old girl presented with a mass in the left side of the abdomen with associated
      dragging pain. Ultrasound Abdomen and CT (computed tomography) confirmed an SPT
      with portal hypertension, with the lesion involving the body and tail of
      pancreas. DISCUSSION: Although few reports are available on SPT with portal
      hypertension, ours is the first report on a benign SPT with sinistral portal
      hypertension treated with a distal pancreatectomy. The presence of portal
      hypertension made the excision of the tumor and delineation of the vessels very
      difficult. However, when great care is taken while handling the dilated vessels,
      dissection can be completed with minimal blood loss. CONCLUSION: Meticulous
      surgical technique along with accurate identification of vasculature will aid in
      the resection. Although some SPTs behave aggressively, most of them are benign
      and patients with SPT have an excellent prognosis.

PMID- 27046102
TI  - A rare case of a transabdominal impalement after a fall from a ladder.
AB  - INTRODUCTION: Impalement injuries are caused by objects that penetrate and remain
      inside the human body. They are rare and often lead to complex surgical problems,
      demanding immediate measures and intensive care. PRESENTATION OF CASE: We report
      a case of a 39 year old male who presented in our emergency department with a
      history of fall from a 3m high ladder, landing on a wooden stick that penetrated
      the patient from his left lumbar region, leading to a trans-abdominal impalement
      injury. DISCUSSION: Nowadays impalement injuries although rare, demonstrate a
      challenging presentation for emergency providers. Their complexity often raises
      concerns about the proper surgical approach and postoperative management. In many
      cases, they may cause severe morbidity or even be lethal. CONCLUSION: The article
      describes a case of a transabdominal impalement injury and pinpoints the
      strategies followed regarding the prehospital care, as well as the intra- and
      postoperative management.

PMID- 27046103
TI  - Inflammatory myofibroblastic tumor of the small intestine: A case report.
AB  - INTRODUCTION: Inflammatory myofibroblastic tumor (IMT) is a rare benign tumor.
      Usually seen in children and adolescents, this inflammatory tumor can affect all
      the organs. PRESENTATION OF CASE: In this case, a five-year-old child experienced
      the sudden onset of symptoms and the enlargement of abdominal mass 20 days before
      referral. The patient did not have any symptoms of nausea, vomit, and abdominal
      pain. In the laparotomy, a large and sticky solid mass, attached to the ileum
      with the mesenteric origin, sized 10*8cm was observed and completely resected.
      DISCUSSION: This tumor rarely emerges in the small intestine, and there are a few
      patients with intestinal manifestation. In this case report, the tumor had an
      origin of the small intestine mesenteric and it had invaded to the ileum.
      CONCLUSION: Despite using some radiographic methods such as medical ultrasound
      and computerized tomography (CT) scan to diagnose the disease, the definitive
      diagnosis is merely possible thorough complete surgical resection.

PMID- 27046104
TI  - Synchronous neuroendocrine tumors in both the pancreas and ileum: A case report.
AB  - INTRODUCTION: Although it is well-known that in multiple endocrine neoplasia type
      1 (MEN 1) disease, multiple endocrine lesions frequently occur, synchronous or
      metachronous neuroendocrine tumors (NETs) in non-MEN 1 patients are extremely
      rare. PRESENTATION OF CASE: An asymptomatic 72-year-old woman with an ileal NET
      was referred to our hospital. Abdominal computed tomography revealed another
      circular tumor within the pancreatic head. She was classified as a non-MEN 1
      patient. An operative procedure was performed with a preoperative diagnosis of
      synchronous NET, which was confirmed by pathological examination. DISCUSSION:
      Both morphologic and immunophenotypic findings were different between in the
      ileum and pancreas. Therefore, it was reasonable to consider that both tumors
      were primary tumors. The synchronous occurrence of these tumors is unusual, and
      it may be considered as a chance occurrence. CONCLUSION: We here report the first
      case of synchronous pancreatic NET and ileal NET in a non-MEN 1 patient.

PMID- 27046105
TI  - A sign on CT that predicts a hazardous ureteral anomaly.
AB  - INTRODUCTION: An aberrant course of the distal ureter can pose a risk of ureteral
      injury during surgery for inguinal hernia repair and other groin operations. In a
      recent case series of inguinoscrotal hernation of the ureter, we found that each
      affected ureter was markedly anterior to the psoas muscle at its mid-point on
      abdominal CT. We hypothesized that this abnormality in the abdominal course of
      the ureter would predict the potentially hazardous aberrant course of the distal
      ureter. PRESENTATION OF CASES: We reviewed all evaluable CT urograms performed at
      St. Louis University Hospital from June 2012 to July 2013 and measured the
      ureteral course at several anatomically fixed points. DISCUSSION: 93% (50/54) of
      ureters deviated by less than 1cm from the psoas muscle in their mid-course (at
      the level of the L4 vertebra). Reasons for anterior deviation of the ureter in
      this study included morbid obesity with prominent retroperitoneal fat, congenital
      renal abnormality, and post-traumatic renal/retroperitoneal hematoma. We
      determined that the optimal level on abdominal CT to detect the displaced ureter
      was the mid-body of the L4 vertebra. CONCLUSION: Anterior deviation of the ureter
      in its mid-course appears to predict inguinoscrotal herniation of the ureter.
      This finding is a sensitive predictor and should raise concern for this anomaly
      in the appropriate clinical setting. It is not entirely specific as morbid
      obesity and congenital anomalies may result in a similar imaging appearance. We
      believe that this association has not been reported previously. Awareness of this
      anomaly can have significant operative implications.

PMID- 27046106
TI  - Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex,
      Gender Identity, and Sexual Orientation.
AB  - CONTEXT: Since the discovery of its central role in reproduction, our functional
      neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly
      based on animal studies. Although sex differences in kisspeptin expression have
      been shown in humans in adulthood, the developmental origin of this sex
      difference is unknown. OBJECTIVES: Our objectives were to determine the
      following: 1) when during development the sex difference in kisspeptin expression
      in the infundibular nucleus would emerge and 2) whether this sex difference is
      related to sexual orientation or transsexuality. DESIGN AND SETTING: Postmortem
      hypothalamic tissues were collected by The Netherlands Brain Bank, and sections
      were stained for kisspeptin by immunohistochemistry. PATIENTS: Hypothalami of 43
      control subjects were categorized into three periods: infant/prepubertal (six
      girls, seven boys), adult (11 women, seven men), and elderly (six aged women, six
      aged men). Eight male-to-female (MTF) transsexuals, three HIV(+) heterosexual
      men, and five HIV(+) homosexual men were also analyzed. MAIN OUTCOME MEASURE: We
      estimated the total number of kisspeptin-immunoreactive neurons within the
      infundibular nucleus. RESULTS: Quantitative analysis confirmed that the human
      infundibular kisspeptin system exhibits a female-dominant sex difference. The
      number of kisspeptin neurons is significantly greater in the infant/prepubertal
      and elderly periods compared with the adult period. Finally, in MTF transsexuals,
      but not homosexual men, a female-typical kisspeptin expression was observed.
      CONCLUSIONS: These findings suggest that infundibular kisspeptin neurons are
      sensitive to circulating sex steroid hormones throughout life and that the sex
      reversal observed in MTF transsexuals might reflect, at least partially, an
      atypical brain sexual differentiation.

PMID- 27046107
TI  - Segmentation of perivascular spaces in 7T MR image using auto-context model with
      orientation-normalized features.
AB  - Quantitative study of perivascular spaces (PVSs) in brain magnetic resonance (MR)
      images is important for understanding the brain lymphatic system and its
      relationship with neurological diseases. One of the major challenges is the
      accurate extraction of PVSs that have very thin tubular structures with various
      directions in three-dimensional (3D) MR images. In this paper, we propose a
      learning-based PVS segmentation method to address this challenge. Specifically,
      we first determine a region of interest (ROI) by using the anatomical brain
      structure and the vesselness information derived from eigenvalues of image
      derivatives. Then, in the ROI, we extract a number of randomized Haar features
      which are normalized with respect to the principal directions of the underlying
      image derivatives. The classifier is trained by the random forest model that can
      effectively learn both discriminative features and classifier parameters to
      maximize the information gain. Finally, a sequential learning strategy is used to
      further enforce various contextual patterns around the thin tubular structures
      into the classifier. For evaluation, we apply our proposed method to the 7T brain
      MR images scanned from 17 healthy subjects aged from 25 to 37. The performance is
      measured by voxel-wise segmentation accuracy, cluster-wise classification
      accuracy, and similarity of geometric properties, such as volume, length, and
      diameter distributions between the predicted and the true PVSs. Moreover, the
      accuracies are also evaluated on the simulation images with motion artifacts and
      lacunes to demonstrate the potential of our method in segmenting PVSs from
      elderly and patient populations. The experimental results show that our proposed
      method outperforms all existing PVS segmentation methods.

PMID- 27046108
TI  - Structural connectivity relates to perinatal factors and functional impairment at
      7years in children born very preterm.
AB  - OBJECTIVE: To use structural connectivity to (1) compare brain networks between
      typically and atypically developing (very preterm) children, (2) explore
      associations between potential perinatal developmental disturbances and brain
      networks, and (3) describe associations between brain networks and functional
      impairments in very preterm children. METHODS: 26 full-term and 107 very preterm
      7-year-old children (born <30weeks' gestational age and/or <1250g) underwent T1-
      and diffusion-weighted imaging. Global white matter fibre networks were produced
      using 80 cortical and subcortical nodes, and edges were created using constrained
      spherical deconvolution-based tractography. Global graph theory metrics were
      analysed, and regional networks were identified using network-based statistics.
      Cognitive and motor function were assessed at 7years of age. RESULTS: Compared
      with full-term children, very preterm children had reduced density, lower global
      efficiency and higher local efficiency. Those with lower gestational age at
      birth, infection or higher neonatal brain abnormality score had reduced
      connectivity. Reduced connectivity within a widespread network was predictive of
      impaired IQ, while reduced connectivity within the right parietal and temporal
      lobes was associated with motor impairment in very preterm children. CONCLUSIONS:
      This study utilised an innovative structural connectivity pipeline to reveal that
      children born very preterm have less connected and less complex brain networks
      compared with typically developing term-born children. Adverse perinatal factors
      led to disturbances in white matter connectivity, which in turn are associated
      with impaired functional outcomes, highlighting novel structure-function
      relationships.

PMID- 27046109
TI  - Reinforcement learning of self-regulated sensorimotor beta-oscillations improves
      motor performance.
AB  - Self-regulation of sensorimotor oscillations is currently researched in
      neurorehabilitation, e.g. for priming subsequent physiotherapy in stroke
      patients, and may be modulated by neurofeedback or transcranial brain
      stimulation. It has still to be demonstrated, however, whether and under which
      training conditions such brain self-regulation could also result in motor gains.
      Thirty-two right-handed, healthy subjects participated in a three-day
      intervention during which they performed 462 trials of kinesthetic motor-imagery
      while a brain-robot interface (BRI) turned event-related beta-band
      desynchronization of the left sensorimotor cortex into the opening of the right
      hand by a robotic orthosis. Different training conditions were compared in a
      parallel-group design: (i) adaptive classifier thresholding and contingent
      feedback, (ii) adaptive classifier thresholding and non-contingent feedback,
      (iii) non-adaptive classifier thresholding and contingent feedback, and (iv) non
      adaptive classifier thresholding and non-contingent feedback. We studied the task
      related cortical physiology with electroencephalography and the behavioral
      performance in a subsequent isometric motor task. Contingent neurofeedback and
      adaptive classifier thresholding were critical for learning brain self-regulation
      which, in turn, led to behavioral gains after the intervention. The acquired
      skill for sustained sensorimotor beta-desynchronization correlated significantly
      with subsequent motor improvement. Operant learning of brain self-regulation with
      a BRI may offer a therapeutic perspective for severely affected stroke patients
      lacking residual hand function.

PMID- 27046110
TI  - Neural correlates of training and transfer effects in working memory in older
      adults.
AB  - As indicated by previous research, aging is associated with a decline in working
      memory (WM) functioning, related to alterations in fronto-parietal neural
      activations. At the same time, previous studies showed that WM training in older
      adults may improve the performance in the trained task (training effect), and
      more importantly, also in untrained WM tasks (transfer effects). However, neural
      correlates of these transfer effects that would improve understanding of its
      underlying mechanisms, have not been shown in older participants as yet. In this
      study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during
      n-back performance and an untrained delayed recognition (Sternberg) task
      following 12sessions (45min each) of adaptive n-back training in older adults.
      The Sternberg task used in this study allowed to test for neural training effects
      independent of specific task affordances of the trained task and to separate
      maintenance from updating processes. Thirty-two healthy older participants (60
      75years) were assigned either to an n-back training or a no-contact control
      group. Before (t1) and after (t2) training/waiting period, both the n-back task
      and the Sternberg task were conducted while BOLD signal was measured using
      functional Magnetic Resonance Imaging (fMRI) in all participants. In addition,
      neuropsychological tests were performed outside the scanner. WM performance
      improved with training and behavioral transfer to tests measuring executive
      functions, processing speed, and fluid intelligence was found. In the training
      group, BOLD signal in the right lateral middle frontal gyrus/caudal superior
      frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and
      the updating condition of the untrained Sternberg task at t2, compared to the
      control group. fMRI findings indicate a training-related increase in processing
      efficiency of WM networks, potentially related to the process of WM updating.
      Performance gains in untrained tasks suggest that transfer to other cognitive
      tasks remains possible in aging.

PMID- 27046111
TI  - SPARK: Sparsity-based analysis of reliable k-hubness and overlapping network
      structure in brain functional connectivity.
AB  - Functional hubs are defined as the specific brain regions with dense connections
      to other regions in a functional brain network. Among them, connector hubs are of
      great interests, as they are assumed to promote global and hierarchical
      communications between functionally specialized networks. Damage to connector
      hubs may have a more crucial effect on the system than does damage to other hubs.
      Hubs in graph theory are often identified from a correlation matrix, and
      classified as connector hubs when the hubs are more connected to regions in other
      networks than within the networks to which they belong. However, the
      identification of hubs from functional data is more complex than that from
      structural data, notably because of the inherent problem of multicollinearity
      between temporal dynamics within a functional network. In this context, we
      developed and validated a method to reliably identify connectors and
      corresponding overlapping network structure from resting-state fMRI. This new
      method is actually handling the multicollinearity issue, since it does not rely
      on counting the number of connections from a thresholded correlation matrix. The
      novelty of the proposed method is that besides counting the number of networks
      involved in each voxel, it allows us to identify which networks are actually
      involved in each voxel, using a data-driven sparse general linear model in order
      to identify brain regions involved in more than one network. Moreover, we added a
      bootstrap resampling strategy to assess statistically the reproducibility of our
      results at the single subject level. The unified framework is called SPARK, i.e.
      SParsity-based Analysis of Reliable k-hubness, where k-hubness denotes the number
      of networks overlapping in each voxel. The accuracy and robustness of SPARK were
      evaluated using two dimensional box simulations and realistic simulations that
      examined detection of artificial hubs generated on real data. Then, test/retest
      reliability of the method was assessed using the 1000 Functional Connectome
      Project database, which includes data obtained from 25 healthy subjects at three
      different occasions with long and short intervals between sessions. We
      demonstrated that SPARK provides an accurate and reliable estimation of k
      hubness, suggesting a promising tool for understanding hub organization in
      resting-state fMRI.

PMID- 27046112
TI  - Functional connectivity and network analysis of midbrain and brainstem nuclei.
AB  - There is limited understanding of how monoamine-producing nuclei within midbrain
      and brainstem contribute to the formation and functional dynamics of brain
      networks across the human neocortex. We used resting state fMRI in 154 healthy
      participants to elucidate patterns of functional connectivity and network
      organization between cortical/subcortical regions and midbrain/brainstem nuclei.
      By means of univariate functional connectivity and graph-based analysis, we show
      that dopaminergic midbrain centers and the serotonergic dorsal raphe nucleus
      (DRN) are functionally integrated with the default mode network (DMN), whereas
      the remaining serotonergic raphe nuclei and the noradrenergic locus coeruleus are
      functionally integrated with the executive-control network (ECN). The majority of
      midbrain/brainstem nuclei show a high level of connectedness to other network
      modules classifying these nuclei as "connector" hubs. The additionally applied
      probabilistic independent component analysis (PICA) broadly corresponded with the
      results of the GT analysis, describing similar functionally-relevant cortical
      networks. Since monoaminergic neurotransmission is essential to neocortical
      function, and represents an important target for pharmacotherapy, our novel
      findings contribute to a comprehensive understanding of the functional
      organization of the human brain.

PMID- 27046113
TI  - Cortical subnetwork dynamics during human language tasks.
AB  - Language tasks require the coordinated activation of multiple subnetworks-groups
      of related cortical interactions involved in specific components of task
      processing. Although electrocorticography (ECoG) has sufficient temporal and
      spatial resolution to capture the dynamics of event-related interactions between
      cortical sites, it is difficult to decompose these complex spatiotemporal
      patterns into functionally discrete subnetworks without explicit knowledge of
      each subnetwork's timing. We hypothesized that subnetworks corresponding to
      distinct components of task-related processing could be identified as groups of
      interactions with co-varying strengths. In this study, five subjects implanted
      with ECoG grids over language areas performed word repetition and picture naming.
      We estimated the interaction strength between each pair of electrodes during each
      task using a time-varying dynamic Bayesian network (tvDBN) model constructed from
      the power of high gamma (70-110Hz) activity, a surrogate for population firing
      rates. We then reduced the dimensionality of this model using principal component
      analysis (PCA) to identify groups of interactions with co-varying strengths,
      which we term functional network components (FNCs). This data-driven technique
      estimates both the weight of each interaction's contribution to a particular
      subnetwork, and the temporal profile of each subnetwork's activation during the
      task. We found FNCs with temporal and anatomical features consistent with
      articulatory preparation in both tasks, and with auditory and visual processing
      in the word repetition and picture naming tasks, respectively. These FNCs were
      highly consistent between subjects with similar electrode placement, and were
      robust enough to be characterized in single trials. Furthermore, the interaction
      patterns uncovered by FNC analysis correlated well with recent literature
      suggesting important functional-anatomical distinctions between processing
      external and self-produced speech. Our results demonstrate that subnetwork
      decomposition of event-related cortical interactions is a powerful paradigm for
      interpreting the rich dynamics of large-scale, distributed cortical networks
      during human cognitive tasks.

PMID- 27046114
TI  - The European DTI Study on Dementia - A multicenter DTI and MRI study on
      Alzheimer's disease and Mild Cognitive Impairment.
AB  - The European DTI Study on Dementia (EDSD) is a multicenter framework created to
      study the diagnostic accuracy and inter-site variability of DTI-derived markers
      in patients with manifest and prodromal Alzheimer's disease (AD). The dynamically
      growing database presently includes 493 DTI, 512 T1-weighted MRI, and 300 FLAIR
      scans from patients with AD dementia, patients with Mild Cognitive Impairment
      (MCI) and matched Healthy Controls, acquired on 13 different scanner platforms.
      The imaging data is publicly available, along with the subjects' demographic and
      clinical characterization. Detailed neuropsychological information, cerebrospinal
      fluid information on biomarkers and clinical follow-up diagnoses are included for
      a subset of subjects. This paper describes the rationale and structure of the
      EDSD, summarizes the available data, and explains how to gain access to the
      database. The EDSD is a useful database for researchers seeking to investigate
      the contribution of DTI to dementia diagnostics.

PMID- 27046115
TI  - Variability of brain anatomy for three common mouse strains.
AB  - The way in which brain structures express different morphologies is not fully
      understood. Here we investigate variability in brain anatomy using ex vivo MRI of
      three common laboratory mouse strains: in two inbred strains (C57BL/6 and 129S6)
      and one outbred strain (CD-1). We use Generalised Procrustes Analysis (GPA) to
      estimate modes of anatomical variability. We find three distinct bilateral modes
      of anatomical surface variability associated with the motor cortex, the anterior
      somatosensory, the retrosplenial and the entorhinal cortex. The modes of
      variability that are associated with the motor cortex and anterior somatosensory
      cortex are predominantly due to genetic, i.e. strain differences. Next, we
      specifically test if a particular strain is more variable. We find that only the
      mode associated with motor cortex size has a slightly larger variance in the
      outbred CD-1 mice compared to the two inbred strains. This suggests that the
      hypothesis that outbred strains are more variable in general is not true for
      brain anatomy and the use of outbred CD-1 mice does probably not come at the
      price of increased variability. Further, we show that the first two principal
      components distinguish between the three strains with 91% accuracy. This
      indicates that neuroanatomical strain differences are captured by considerably
      fewer dimensions than necessary for atlas-based or voxel-wise testing.
      Statistical comparisons based on shape models could thus be a powerful complement
      to traditional atlas and voxel-based methods at detecting gene-related brain
      differences in mice. Finally, we find that the principal components of individual
      brain structures are correlated, suggesting a tightly coupled network of
      interdependent developmental trajectories. These results raise the question to
      what degree neuroanatomical variability is directly genetically determined or the
      result of experience and epigenetic mechanisms.

PMID- 27046116
TI  - Erratum.

PMID- 27046118
TI  - Binocular Rivalry Measured 2 Hours After Occlusion Therapy Predicts the Recovery
      Rate of the Amblyopic Eye in Anisometropic Children.
AB  - PURPOSE: Recent studies on adults have shown that short-term monocular
      deprivation boosts the deprived eye signal in binocular rivalry, reflecting
      homeostatic plasticity. Here we investigate whether homeostatic plasticity is
      present also during occlusion therapy for moderate amblyopia. METHODS: Binocular
      rivalry and visual acuity (using Snellen charts for children) were measured in 10
      children (mean age 6.2 +/- 1 years) with moderate anisometropic amblyopia before
      the beginning of treatment and at four intervals during occlusion therapy (2
      hours, 1, 2, and 5 months). Visual stimuli were orthogonal gratings presented
      dichoptically through ferromagnetic goggles and children reported verbally visual
      rivalrous perception. Bangerter filters were applied on the spectacle lens over
      the best eye for occlusion therapy. RESULTS: Two hours of occlusion therapy
      increased the nonamblyopic eye predominance over the amblyopic eye compared with
      pretreatment measurements, consistent with the results in adults. The boost of
      the nonamblyopic eye was still present after 1 month of treatment, steadily
      decreasing afterward to reach pretreatment levels after 2 months of continuous
      occlusion. Across subjects, the increase in nonamblyopic eye predominance
      observed after 2 hours of occlusion correlated (rho = -0.65, P = 0.04) with the
      visual acuity improvement of the amblyopic eye measured after 2 months of
      treatment. CONCLUSIONS: Homeostatic plasticity operates during occlusion therapy
      for moderate amblyopia and the increase in nonamblyopic eye dominance observed at
      the beginning of treatment correlates with the amblyopic eye recovery rate. These
      results suggest that binocular rivalry might be used to monitor visual cortical
      plasticity during occlusion therapy, although further investigations on larger
      clinical populations are needed to validate the predictive power of the
      technique.

PMID- 27046119
TI  - Enzymatic Resistance of Corneas Crosslinked Using Riboflavin in Conjunction With
      Low Energy, High Energy, and Pulsed UVA Irradiation Modes.
AB  - PURPOSE: To investigate the effect of various riboflavin/ultraviolet light (UVA)
      crosslinking (CXL) protocols on corneal enzymatic resistance. METHODS: A total of
      66 enucleated porcine eyes, with the corneal epithelium removed, were divided
      into 6 groups. Group 1 remained untreated. Groups 2 to 6 received
      riboflavin/dextran for 30 minutes. Group 3 underwent standard CXL (SCXL) with 3
      mW/cm(2) UVA for 30 minutes (total energy dose 5.4 J/cm(2)). Groups 4 and 5
      underwent high intensity CXL (HCXL) using 30 mW/cm(2) UVA for 3 minutes (5.4
      J/cm(2)) and 30 mW/cm(2) for 4 minutes (7.2 J/cm(2)), respectively. Group 6 was
      exposed to 8 minutes of 30 mW/cm(2) UVA in a 10-second on/10-second off pulsed
      radiation mode (p-HCXL; 7.2 J/cm(2)). A central 8-mm disk from each cornea was
      submerged in pepsin digest solution at 23 degrees C and measured daily. After 13
      days, the dry weight was recorded from 5 samples in each group. RESULTS: The CXL
      treated corneas took longer to digest than nonirradiated corneas (P < 0.0001).
      Differences in digestion time also were observed between CXL groups, such that,
      HCXL (5.4 J/cm(2)) < SCXL (5.4 J/cm(2)) < HCXL (7.2 J/cm(2)) < p-HCXL (7.2
      J/cm(2); P < 0.0001). The dry weight of the SCXL (5.4 J/cm(2)) group was higher
      than the HCXL (5.4 and 7.2 J/cm(2); P < 0.001) and p-HCXL 7.2 J/cm(2) (P <0.05)
      groups. No difference was detected between the HCXL and p-HCXL 7.2 J/cm(2)
      groups. CONCLUSIONS: The intensity and distribution of the crosslinks formed
      within the cornea vary with different UVA protocols. The precise location and
      amount of crosslinking needed to prevent disease progression is unknown.

PMID- 27046120
TI  - Interphotoreceptor Retinoid-Binding Protein Mitigates Cellular Oxidative Stress
      and Mitochondrial Dysfunction Induced by All-trans-Retinal.
AB  - PURPOSE: Point and null mutations in interphotoreceptor retinoid-binding protein
      (IRBP) cause retinal dystrophy in affected patients and IRBP-deficient mice with
      unknown mechanism. This study investigated whether IRBP protects cells from
      damages induced by all-trans-retinal (atRAL), which was increased in the Irbp(-/
      ) retina. METHODS: Wild-type and Irbp(-/-) mice retinal explants in buffer with
      or without purified IBRP were exposed to 800 lux light for different times and
      subjected to retinoid analysis by high-performance liquid chromatography. Purity
      of IRBP was determined by Coomassie Brilliant Blue staining and immunoblot
      analysis. Cellular damages induced by atRAL in the presence or absence of IRBP
      were evaluated in the mouse photoreceptor-derived 661W cells. Cell viability and
      death were measured by 3-(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) and TUNEL assays. Expression and modification
      levels of retinal proteins were determined by immunoblot analysis. Intracellular
      reactive oxygen species (ROS) and nitric oxide (NO) were detected with
      fluorogenic dyes and confocal microscopy. Mitochondrial membrane potential was
      analyzed by using JC-1 fluorescent probe and a flow cytometer. RESULTS: Content
      of atRAL in Irbp(-/-) retinal explants exposed to light for 40 minutes was
      significantly higher than that in wild-type retinas under the same light
      conditions. All-trans-retinal caused increase in cell death, tumor necrosis
      factor activation, and Adam17 upregulation in 661W cells. NADPH oxidase-1 (NOX1)
      upregulation, ROS generation, NO-mediated protein S-nitrosylation, and
      mitochondrial dysfunction were also observed in 661W cells treated with atRAL.
      These cytotoxic effects were significantly attenuated in the presence of IRBP.
      CONCLUSIONS: Interphotoreceptor retinoid-binding protein is required for
      preventing accumulation of retinal atRAL, which causes inflammation, oxidative
      stress, and mitochondrial dysfunction of the cells.

PMID- 27046122
TI  - Differences in Relationship Between Macular Inner Retinal Layer Thickness and
      Retinal Sensitivity in Eyes With Early and Progressed Glaucoma.
AB  - PURPOSE: To determine if the relationship between retinal sensitivity and macular
      inner retinal layer thickness differs between primary open-angle glaucoma (POAG)
      with mild and advanced central visual field (VF) damage. METHODS: One eye of 153
      POAG patients was included. Using spectral-domain optical coherence tomography,
      we measured the average thickness of the macular ganglion cell-inner plexiform
      layers (GCIPLT) and the macular nerve fiber layer/GCIPL (ganglion cell complex
      [GCCT]) in a 0.9-mm-diameter ganglion cell displacement-adjusted circular area
      corresponding to the four central test points of the Humphrey Perimeter 24-2
      program and correlated the results with the average retinal sensitivity
      (1/Lambert) at the corresponding test points, with adjustment for other
      confounding factors. RESULTS: Ninety-three eyes had mild central and 60 eyes
      advanced central VF damage with an average total deviation (TD) of the four test
      points of greater than or equal to -4 decibels (dB) (mild group) and less than -4
      dB (more severe group), respectively; the average mean deviations were -3.0 and 
      9.8 dB, respectively. In the mild group, the GCCT and GCIPLT were correlated
      significantly and positively with the average retinal sensitivity with partial
      regression coefficient of 0.007 and 0.005, respectively, and in the more severe
      group with partial regression coefficient of 0.019 = 0.007 + 0.012 (P = 0.007)
      and 0.010 = 0.005 + 0.005 (P = 0.078), respectively. The axial length and disc
      size were correlated with GCIPLT with marginal significance (P = 0.052 and P =
      0.042). CONCLUSIONS: The relationship between the macular GCC and GCIPL thickness
      and retinal sensitivity at the corresponding retinal areas differed between POAG
      with mild and advanced central VF damage.

PMID- 27046121
TI  - Defective Angiogenesis and Intraretinal Bleeding in Mouse Models With Disrupted
      Inner Retinal Lamination.
AB  - PURPOSE: Abnormal retinal angiogenesis leads to visual impairment and blindness.
      Understanding how retinal vessels develop normally has dramatically improved
      treatments for people with retinal vasculopathies, but additional information
      about development is required. Abnormal neuron patterning in the outer retina has
      been shown to result in abnormal vessel development and blindness, for example,
      in people and mouse models with Crumbs homologue 1 (CRB1) mutations. In this
      study, we report and characterize a mouse model of inner retinal lamination
      disruption and bleeding, the Down syndrome cell adhesion molecule (Dscam) mutant,
      and test how neuron-neurite placement within the inner retina guides development
      of intraretinal vessels. METHODS: Bax mutant mice (increased neuron cell number),
      Dscam mutant mice (increased neuron cell number, disorganized lamination), Fat3
      mutant mice (disorganized neuron lamination), and Dscam gain-of-function mice
      (Dscam(GOF)) (decreased neuron cell number) were used to manipulate neuron
      placement and number. Immunohistochemistry was used to assay organization of
      blood vessels, glia, and neurons. In situ hybridization was used to map the
      expression of angiogenic factors. RESULTS: Significant changes in the
      organization of vessels within mutant retinas were found. Displaced neurons and
      microglia were associated with the attraction of vessels. Using Fat3 mutant and
      Dscam(GOF) retinas, we provide experimental evidence that vessel branching is
      induced at the neuron-neurite interface, but that other factors are required for
      full plexus layer formation. We further demonstrate that the displacement of
      neurons results in the mislocalization of angiogenic factors. CONCLUSIONS: Inner
      retina neuron lamination is required for development of intraretinal vessels.

PMID- 27046123
TI  - Retinal Pigment Epithelial Features in Central Serous Chorioretinopathy
      Identified by Polarization-Sensitive Optical Coherence Tomography.
AB  - PURPOSE: To determine the subclinical RPE lesions detected by tissue selective
      polarization-sensitive optical coherence tomography (PS-OCT) in eyes with central
      serous chorioretinopathy (CSC) and to compare PS-OCT findings to current imaging
      standards. METHODS: In this prospective observational case series, individuals
      with unilateral or bilateral active CSC were imaged using PS-OCT at baseline and
      after resolution of serous retinal detachment. Features seen on PS-OCT were
      compared with corresponding lesions as seen on conventional, intensity-based
      spectral-domain OCT (SD-OCT), fluorescein angiography, and indocyanine green
      angiography (ICGA). Features of RPE evaluated by PS-OCT were as follows: area and
      volume of pigment epithelium detachment (PED), presence of RPE aggregations, RPE
      skip lesions, RPE thickening, and RPE atrophy. RESULTS: Twenty-five study eyes
      and 23 fellow eyes of 25 participants (2 women, 23 men; mean age +/- standard
      deviation = 40.5 +/- 7.4 years) were included and followed for 6.1 +/- 3 months.
      Study eyes and fellow eyes with recurrent CSC showed more RPE abnormalities in PS
      OCT than eyes with acute CSC, which correlated well with lesions in ICGA. Closure
      of the leakage site was observed only in eight (32%) eyes after resolution of
      subretinal fluid (SRF). All study eyes showed widespread RPE aggregates and 23
      (92%) eyes showed RPE skip lesions after resolution of SRF. CONCLUSIONS: Features
      of RPE indicative of previous episodes of CSC detected by PS-OCT correspond well
      to choroidal lesions in ICGA. In addition, noninvasive PS-OCT imaging enables
      detection of RPE microrips and aggregations invisible to clinical examination or
      SD-OCT, thus providing valuable information about disease processes in vivo.

PMID- 27046124
TI  - Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a
      Mouse Model of Juvenile Hemochromatosis.
AB  - PURPOSE: Hemochromatosis, an iron-overload disease, occurs as adult and juvenile
      types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone
      morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv(
      /-) mice accumulate excess iron in retina and exhibit aberrant vascularization
      and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We
      hypothesized that Hjv(-/-) retinas have increased BMP signaling and increased
      GPR91 expression as the basis of angiomas. METHODS: Expression of GPR91 was
      examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv(-/-)
      mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91
      expression was investigated in ARPE-19 cells, and wild-type and Hjv(-/-) pRPE
      cells. Succinate was used to activate GPR91 and determine the effects of GPR91
      signaling on VEGF expression. Signaling of BMP6 was studied by the expression of
      Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with
      GPR91 promoter was studied by ChIP. RESULTS: Expression of GPR91 was higher in
      Hjv(-/-) retinas and RPE than in wild-type counterparts. Unexpectedly, BMP
      signaling was increased, not decreased, in Hjv(-/-) retinas and RPE. Bone
      morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP
      signaling in Hjv(-/-) retinas was likely responsible for GPR91 upregulation.
      Exposure of RPE to excess iron and succinate as well as BMP6 and succinate
      increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction
      of pSmad4 with GPR91 promoter in RPE. CONCLUSIONS: G-protein-coupled receptor 91
      is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus
      underscoring a role for excess iron and hemochromatosis in abnormal retinal
      vascularization.

PMID- 27046126
TI  - Unclear role of human papillomavirus infection in response to adjuvant
      radiotherapy: conflicting results on the prognostic significance of irradiation
      in vulvar cancer patients with lymph node metastasis.

PMID- 27046125
TI  - In Vivo Functionality of a Corneal Endothelium Transplanted by Cell-Injection
      Therapy in a Feline Model.
AB  - PURPOSE: To evaluate the functionality of a corneal endothelium reconstituted by
      injection of corneal endothelial cells (CEC) in the anterior chamber of a feline
      model. METHODS: We operated the right eyes of 16 animals. Eight underwent central
      endothelial scraping and injection with 2 * 10(5) (n = 4) or 1 * 10(6) (n = 4)
      feline CEC supplemented with Y-27632 and labeled with 3,3'-Dioctadecyl-5,5'-Di(4
      Sulfophenyl)Oxacarbocyanine (SP-DiOC18[3] or DiOC). After total endothelial
      scraping, two eyes were injected with 1 * 10(6) labeled CEC and Y-27632. The
      central (n = 3) or entire (n = 3) endothelium was scraped in six eyes followed by
      Y-27632 injection without CEC. Subjects were positioned eyes down for 3 hours.
      Outcomes included graft transparency, pachymetry, CEC morphometry, histology,
      electron microscopy, and function and wound healing-related protein
      immunostaining. RESULTS: Postoperatively, corneas grafted with 2 * 10(5) CEC and
      centrally scraped controls displayed the best transparency and pachymetry.
      Corneas grafted with 1 * 10(6) CEC yielded intermediate results. Entirely scraped
      controls remained hazy and thick. Histopathology revealed a confluent endothelial
      monolayer expressing sodium-potassium adenosine triphosphatase (Na(+)/K(+)
      ATPase) and zonula occludens-1 (ZO-1) in corneas grafted with 2 * 10(5) CEC and
      centrally scraped controls, a nonuniform endothelial multilayer without
      expression of functional proteins in centrally scraped corneas grafted with 1 *
      10(6) CEC, and a nonfunctional fibrotic endothelium in entirely scraped grafts
      and controls. Expression of DiOC in grafts was scarce. CONCLUSIONS: Injected CEC
      contributed little to the incompletely functional endothelium of grafted corneas.
      Y-27632 injection without CEC following scraping reconstituted the healthiest
      endothelium. Further studies investigating the therapeutic effect of Y-27632
      alone are needed to validate these conclusions.

PMID- 27046127
TI  - Mapping Cannabinoid 1 Receptor Allosteric Site(s): Critical Molecular Determinant
      and Signaling Profile of GAT100, a Novel, Potent, and Irreversibly Binding Probe.
AB  - One of the most abundant G-protein coupled receptors (GPCRs) in brain, the
      cannabinoid 1 receptor (CB1R), is a tractable therapeutic target for treating
      diverse psychobehavioral and somatic disorders. Adverse on-target effects
      associated with small-molecule CB1R orthosteric agonists and inverse
      agonists/antagonists have plagued their translational potential. Allosteric CB1R
      modulators offer a potentially safer modality through which CB1R signaling may be
      directed for therapeutic benefit. Rational design of candidate, druglike CB1R
      allosteric modulators requires greater understanding of the architecture of the
      CB1R allosteric endodomain(s) and the capacity of CB1R allosteric ligands to tune
      the receptor's information output. We have recently reported the synthesis of a
      focused library of rationally designed, covalent analogues of Org27569 and
      PSNCBAM-1, two prototypic CB1R negative allosteric modulators (NAMs). Among the
      novel, pharmacologically active CB1R NAMs reported, the isothiocyanate GAT100
      emerged as the lead by virtue of its exceptional potency in the [(35)S]GTPgammaS
      and beta-arrestin signaling assays and its ability to label CB1R as a covalent
      allosteric probe with significantly reduced inverse agonism in the
      [(35)S]GTPgammaS assay as compared to Org27569. We report here a comprehensive
      functional profiling of GAT100 across an array of important downstream cell
      signaling pathways and analysis of its potential orthosteric probe-dependence and
      signaling bias. The results demonstrate that GAT100 is a NAM of the orthosteric
      CB1R agonist CP55,940 and the endocannabinoids 2-arachidonoylglycerol and
      anandamide for beta-arrestin1 recruitment, PLCbeta3 and ERK1/2 phosphorylation,
      cAMP accumulation, and CB1R internalization in HEK293A cells overexpressing CB1R
      and in Neuro2a and STHdh(Q7/Q7) cells endogenously expressing CB1R.
      Distinctively, GAT100 was a more potent and efficacious CB1R NAM than Org27569
      and PSNCBAM-1 in all signaling assays and did not exhibit the inverse agonism
      associated with Org27569 and PSNCBAM-1. Computational docking studies implicate
      C7.38(382) as a key feature of GAT100 ligand-binding motif. These data help
      inform the engineering of newer-generation, druggable CB1R allosteric modulators
      and demonstrate the utility of GAT100 as a covalent probe for mapping structure
      function correlates characteristic of the druggable CB1R allosteric space.

PMID- 27046128
TI  - An Exploratory Study into Objective and Reported Characteristics of Neuropathic
      Pain in Women with Chronic Pelvic Pain.
AB  - Chronic pelvic pain (CPP) affects 5.7-26.6% women worldwide. 55% have no obvious
      pathology and 40% have associated endometriosis. Neuropathic pain (NeP) is pain
      arising as a consequence of a lesion/disease affecting the somatosensory system.
      The prevalence of NeP in women with CPP is not known. The diagnosis of NeP is
      challenging because there is no gold-standard assessment. Questionnaires have
      been used in the clinical setting to diagnose NeP in other chronic pain
      conditions and quantitative sensory testing (QST) has been used in a research
      setting to identify abnormal sensory function. We aimed to determine if women
      with chronic pelvic pain (CPP) have a neuropathic pain (NeP) component to their
      painful symptoms and how this is best assessed. We performed an exploratory
      prospective cohort study of 72 pre-menopausal women with a diagnosis of CPP. They
      underwent a clinician completed questionnaire (DN4) and completed the S-LANSS and
      PainDETECTTM questionnaires. Additionally QST testing was performed by a
      clinician. They also completed a patient acceptability questionnaire. Clinical
      features of NeP were identified by both questionnaires and QST. Of the women who
      were NeP positive, 56%, 35% and 26% were identified by the S-LANSS, DN4 and
      PainDETECTTM respectively. When NeP was identified by questionnaire, the
      associated laparoscopy findings were similar irrespective of which questionnaire
      was used. No subject had entirely unchanged QST parameters. There were distinct
      loss and gain subgroups, as well as mixed alteration in function, but this was
      not necessarily clinically significant in all patients. 80% of patients were
      confident that questionnaires could diagnose NeP, and 90% found them easy to
      complete. Early identification of NeP in women with CPP with a simple
      questionnaire could facilitate targeted therapy with neuromodulators, which are
      cheap, readily available, and have good safety profiles. This approach could
      prevent unnecessary or fertility-compromising surgery and prolonged treatment
      with hormones. 

PMID- 27046129
TI  - Cardiovascular Safety Warnings and the Prescribing of Varenicline: An Interrupted
      Time-series Analysis.

PMID- 27046130
TI  - The Authors Respond.

PMID- 27046131
TI  - Goat's Milk, Plant-based Milk, Cow's Milk, and Serum 25-hydroxyvitamin D Levels
      in Early Childhood.

PMID- 27046132
TI  - Structural variety in zinc telluro-phosphates: syntheses, crystal structures and
      characterizations of Sr2Zn3Te2P2O14, Pb2Zn3Te2P2O14 and Ba2Zn2TeP2O11.
AB  - Three new zinc telluro-phosphates, Sr2Zn3Te2P2O14 (1), Pb2Zn3Te2P2O14 (2) and
      Ba2Zn2TeP2O11 (3), were grown by flux method, and their crystal structures were
      solved by X-ray diffraction method. Although all three crystals crystallize into
      the same space group P21/c with similar chemical compositions, they exhibit
      different topology structure types. 1 features a two-dimensional layered
      structure with the connection of TeO4 and (Zn3TeP2O18)(16-) 12-membered rings
      (MRs), which are composed of planar square and tetrahedral configuration ZnO4
      groups, tetrahedral PO4 and seesaw TeO4. Due to lone-pair Coulomb repulsion of
      Pb(2+), the structure of 2, which is also composed of unbalanced seesaw TeO4 and
      ZnO4 groups and distorted PO4 tetrahedra, is slightly different from that of its
      analog 1. Compound 3 exhibits a complicated three-dimensional network with
      (Zn2PO9)(9-) 6-MRs and (Zn2Te2O10)(8-) 8-MRs built from distorted tetrahedral
      ZnO4 and PO4 groups and trigonal pyramidal TeO3 units. According to UV-vis-NIR
      diffuse reflectance spectra, compounds 1, 2 and 3 are highly transparent in the
      range of 450 to 2500 nm with a UV cut-off of 275 nm, 330 nm and 278 nm,
      respectively. In addition, the characterizations, including thermal analyses, XPS
      measurement and dipole moment calculations, are also reported.

PMID- 27046133
TI  - Evaluation of High-Yield Purification Methods on Monodisperse PEG-Grafted Iron
      Oxide Nanoparticles.
AB  - Fundamental research on nanoparticle (NP) interactions and development of next
      generation biomedical NP applications relies on synthesis of monodisperse,
      functional, core-shell nanoparticles free of residual dispersants with truly
      homogeneous and controlled physical properties. Still, synthesis and purification
      of e.g. such superparamagnetic iron oxide NPs remain a challenge. Comparing the
      success of different methods is marred by the sensitivity of analysis methods to
      the purity of the product. We synthesize monodisperse, oleic acid (OA)-capped,
      Fe3O4 NPs in the superparamagnetic size range (3-10 nm). Ligand exchange of OA
      for poly(ethylene glycol) (PEG) was performed with the PEG irreversibly grafted
      to the NP surface by a nitrodopamine (NDA) anchor. Four different methods were
      investigated to remove excess ligands and residual OA: membrane centrifugation,
      dialysis, size exclusion chromatography, and precipitation combined with magnetic
      decantation. Infrared spectroscopy and thermogravimetric analysis were used to
      determine the purity of samples after each purification step. Importantly, only
      magnetic decantation yielded pure NPs at high yields with sufficient grafting
      density for biomedical applications (~1 NDA-PEG(5 kDa)/nm(2), irrespective of
      size). The purified NPs withstand challenging tests such as temperature cycling
      in serum and long-term storage in biological buffers. Dynamic light scattering,
      transmission electron microscopy, and small-angle X-ray scattering show stability
      over at least 4 months also in serum. The successful synthesis and purification
      route is compatible with any conceivable functionalization for biomedical or
      biomaterial applications of PEGylated Fe3O4 NPs.

PMID- 27046134
TI  - Characterizing the Impact of Extreme Heat on Mortality, Karachi, Pakistan, June
      2015.
AB  - Introduction Karachi, Pakistan was affected by a heat wave in June 2015 during
      the Muslim holy month of Ramadan. Many media reports attributed the excess deaths
      in part to the practice of daylight fasting during Ramadan. As much of the
      published research reports on heat-related mortality in Europe and the United
      States, an exploration of the effects of extreme heat on residents of a South
      Asian mega-city address a gap in current disaster research. Hypothesis/Problem
      This report investigated potential risk factors for excess mortality associated
      with the June 2015 heat wave in Karachi, Pakistan. METHODS: Data were obtained
      through manual review of death certificates at public hospitals and private
      clinics in Karachi, Pakistan, conducted from July 1 through July 31, 2015 by a
      trained physician. Demographic data for any deaths with a primary cause of death
      of heat-related illness were recorded in Microsoft Excel (Microsoft Corp.;
      Redmond, Washington USA). EpiSheet (2012; Rothman. Modern Epidemiology.
      Lippincott Williams & Wilkins; Philadelphia, Pennsylvania USA) was used to
      calculate risk differences (RD), rate ratios (RR), and 95% confidence intervals
      (95% CI). RESULTS: Overall, residents of Karachi were approximately 17 times as
      likely to die of a heat-related cause of death during June 2015 (RR=17.68; 95%
      CI, 13.87-22.53) when compared with the reference period of June 2014. Residents
      with a monthly income lower than 20,000 Pakistani Rupees (US $196; RD=0.03; 95%
      CI, 0.01-0.05) and those with less than a fifth grade education (RD=0.03; 95% CI,
      0.00-0.05) were at significantly higher risk of death during the 2015 heat wave
      compared to the reference period. CONCLUSION: Fasting during Ramadan was not a
      significant risk factor for mortality from heat-related causes during the Karachi
      heat wave of June 2015. A large number of excess deaths were reported across all
      demographic groups, which due to the burden of record keeping in an under
      resourced health system during a public health emergency, are almost certainly an
      underestimate. Ghumman U , Horney J . Characterizing the impact of extreme heat
      on mortality, Karachi, Pakistan, June 2015. Prehosp Disaster Med. 2016;31(3):263
      266.

PMID- 27046135
TI  - Central nervous system involvement in T-cell lymphoma: A single center
      experience.
AB  - Background We characterized the incidence of central nervous system (CNS)
      involvement, risk factors and outcome in a large single institution dataset of
      peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL
      database at Memorial Sloan Kettering Cancer Center. We identified 231 patients
      with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up
      or an event defined as relapse or death. Results Histologies included peripheral
      T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic
      (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%),
      extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL)
      (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS
      disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B
      cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months
      (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal
      methotrexate). Rates of CNS involvement were not different in patients who
      received prophylaxis. Univariate analysis identified stage III-IV, bone marrow
      involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On
      multivariate analysis, >1 extranodal site and international prognostic index
      (IPI) >= 3 were predictive for CNS involvement. The median survival of patients
      with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse
      rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with
      CNS involvement is poor and risk factors include: >1 extra nodal site and IPI
      >=3. 

PMID- 27046136
TI  - Oil-in-Oil Emulsions Stabilized by Asymmetric Polymersomes Formed by AC + BC
      Block Polymer Co-Assembly.
AB  - We demonstrate a facile route to asymmetric polymersomes by blending AC and BC
      block copolymers in oil-in-oil emulsions containing polystyrene (PS) and
      polybutadiene (PB) in chloroform (CHCl3). Polymersomes were prepared by mixing
      polystyrene-b-poly(ethylene oxide) (SO) and polybutadiene-b-poly(ethylene oxide)
      (BO) in the oil-in-oil emulsion, where the droplets and continuous phase are PS-
      and PB-rich, respectively. The polymersome structure was directly visualized
      using dye-labeled SO and BO with confocal fluorescence microscopy; SO and BO with
      a high O block fraction co-assemble to produce asymmetric polymersomes. As the O
      block is insoluble in both PS and PB, we infer that the detailed structure of the
      polymersomes is a bilayer in which the S and B blocks face the PS-inner and PB
      outer phases, respectively, while the common O blocks form the core membrane.
      This structure is only observed for sufficiently long O blocks. It is remarkable
      that although all the polymers are soluble in CHCl3, such elaborate structures
      are created by straightforward co-assembly. These asymmetric polymersomes should
      provide robust bilayer membranes around emulsion droplets, leading to stable
      nanoscopic dispersions of two fluids. 

PMID- 27046137
TI  - Single-cell RNA sequencing: revealing human pre-implantation development,
      pluripotency and germline development.
AB  - Early human development is a dynamic, heterogeneous, complex and multidimensional
      process. During the first week, the single-cell zygote undergoes eight to nine
      rounds of cell division generating the multicellular blastocyst, which consists
      of hundreds of cells forming spatially organized embryonic and extra-embryonic
      tissues. At the level of transcription, degradation of maternal RNA commences at
      around the two-cell stage, coinciding with embryonic genome activation. Although
      numerous efforts have recently focused on delineating this process in humans,
      many questions still remain as thorough investigation has been limited by ethical
      issues, scarce availability of human embryos and the presence of minute amounts
      of DNA and RNA. In vitro cultures of embryonic stem cells provide some insight
      into early human development, but such studies have been confounded by analysis
      on a population level failing to appreciate cellular heterogeneity. Recent
      technical developments in single-cell RNA sequencing have provided a novel and
      powerful tool to explore the early human embryo in a systematic manner. In this
      review, we will discuss the advantages and disadvantages of the techniques
      utilized to specifically investigate human development and consider how the
      technology has yielded new insights into pre-implantation development, embryonic
      stem cells and the establishment of the germ line. 

PMID- 27046138
TI  - Time is no healer: increasing restoration age does not lead to improved benthic
      invertebrate communities in restored river reaches.
AB  - Evidence for successful restoration of riverine communities is scarce,
      particularly for benthic invertebrates. Among the multitude of reasons discussed
      so far for the lack of observed effects is too short of a time span between
      implementation and monitoring. Yet, studies that explicitly focus on the
      importance of restoration age are rare. We present a comprehensive study based on
      44 river restoration projects in Germany, focusing on standardized benthic
      invertebrate sampling. A broad gradient ranging from 1 to 25years in restoration
      age was available. In contrast to clear improvements in habitat heterogeneity,
      benthic community responses to restoration were inconsistent when compared to
      control sections. Taxon richness increased in response to restoration, but
      abundance, diversity and various assessment metrics did not respond clearly.
      Restoration age was a poor predictor of community composition and community
      change, as no significant linear responses could be detected using 34 metrics.
      Moreover, only 5 out of 34 tested metrics showed non-linear shifts at restoration
      ages of 2 to 3years. This might be interpreted as an indication of a post
      restoration disturbance followed by a re-establishment of pre-restoration
      conditions. BIO-ENV analysis and fourth-corner modeling underlined the low
      importance of restoration age, but revealed high importance of catchment-scale
      characteristics (e.g., ecoregion, catchment size and land use) in controlling
      community composition and community change. Overall, a lack of time for community
      development did not appear to be the ultimate reason for impaired benthic
      invertebrate communities. Instead, catchment-scale characteristics override the
      effectiveness of restoration. To enhance the ecological success of future river
      restoration projects, we recommend improving water quality conditions and
      catchment-scale processes (e.g., connectivity and hydrodynamics) in addition to
      restoring local habitat structure.

PMID- 27046139
TI  - Outdoor urban nanomaterials: The emergence of a new, integrated, and critical
      field of study.
AB  - Engineered nanomaterials (ENMs) are currently widely incorporated in the outdoor
      urban environmental fabric and numerous new applications and products containing
      ENMs are expected in the future. As has been shown repeatedly, products
      containing ENMs have the potential, at some point in their lifetime, to release
      ENMs into their surrounding environment. However, the expanding body in
      environmental nanomaterial research has not yet shifted toward ENMs in the
      context of the complex outdoor urban environment. This is especially surprising
      because the world's human populations are on a steady march toward more and more
      urbanization and technological development, accompanied with increased
      applications for ENMs in the outdoor urban environment. Our objective for this
      paper is therefore to review, assess, and provide new information in this
      emerging field. We provide an overview of nanomaterials (NMs, encompassing both
      ENMs and incidental nanomaterials, INMs) that are likely to be released in the
      urban environment from outdoor sources by discussing 1) the applications of ENMs
      that may lead to release of ENMs in urban areas, 2) the recently published data
      on the release of ENMs from novel nano-enabled applications in the outdoor urban
      environment, 3) the available literature on the occurrence of INMs in the
      atmosphere and within/on dust particles, and 4) the potential pathways and fate
      of NMs in the outdoor urban environment. This review is then followed by three
      case studies demonstrating the importance of NMs in the outdoor urban
      environment. The first and second case studies illustrate the occurrence of NMs
      in urban dust and stormwater ponds, respectively, whereas the third case study
      discusses the lessons learned from the release of NMs (e.g. Pt, ph and Rh) from
      automotive vehicle catalytic convertors. This article ends with a discussion of
      the research priorities needed to advance this emerging field of "outdoor urban
      nanomaterials" and to assess the potential risks of NMs in the context of urban
      environments.

PMID- 27046140
TI  - Human health risk assessment of heavy metals in urban stormwater.
AB  - Toxic chemical pollutants such as heavy metals (HMs) are commonly present in
      urban stormwater. These pollutants can pose a significant risk to human health
      and hence a significant barrier for urban stormwater reuse. The primary aim of
      this study was to develop an approach for quantitatively assessing the risk to
      human health due to the presence of HMs in stormwater. This approach will lead to
      informed decision making in relation to risk management of urban stormwater
      reuse, enabling efficient implementation of appropriate treatment strategies. In
      this study, risks to human health from heavy metals were assessed as hazard index
      (HI) and quantified as a function of traffic and land use related parameters.
      Traffic and land use are the primary factors influencing heavy metal loads in the
      urban environment. The risks posed by heavy metals associated with total solids
      and fine solids (<150MUm) were considered to represent the maximum and minimum
      risk levels, respectively. The study outcomes confirmed that Cr, Mn and Pb pose
      the highest risks, although these elements are generally present in low
      concentrations. The study also found that even though the presence of a single
      heavy metal does not pose a significant risk, the presence of multiple heavy
      metals could be detrimental to human health. These findings suggest that
      stormwater guidelines should consider the combined risk from multiple heavy
      metals rather than the threshold concentration of an individual species.
      Furthermore, it was found that risk to human health from heavy metals in
      stormwater is significantly influenced by traffic volume and the risk associated
      with stormwater from industrial areas is generally higher than that from
      commercial and residential areas.

PMID- 27046141
TI  - Effect of sugarcane cropping systems on herbicide losses in surface runoff.
AB  - Herbicide runoff from cropping fields has been identified as a threat to the
      Great Barrier Reef ecosystem. A field investigation was carried out to monitor
      the changes in runoff water quality resulting from four different sugarcane
      cropping systems that included different herbicides and contrasting tillage and
      trash management practices. These include (i) Conventional - Tillage (beds and
      inter-rows) with residual herbicides used; (ii) Improved - only the beds were
      tilled (zonal) with reduced residual herbicides used; (iii) Aspirational -
      minimum tillage (one pass of a single tine ripper before planting) with trash
      mulch, no residual herbicides and a legume intercrop after cane establishment;
      and (iv) New Farming System (NFS) - minimum tillage as in Aspirational practice
      with a grain legume rotation and a combination of residual and knockdown
      herbicides. Results suggest soil and trash management had a larger effect on the
      herbicide losses in runoff than the physico-chemical properties of herbicides.
      Improved practices with 30% lower atrazine application rates than used in
      conventional systems produced reduced runoff volumes by 40% and atrazine loss by
      62%. There were a 2-fold variation in atrazine and >10-fold variation in
      metribuzin loads in runoff water between reduced tillage systems differing in
      soil disturbance and surface residue cover from the previous rotation crops,
      despite the same herbicide application rates. The elevated risk of offsite losses
      from herbicides was illustrated by the high concentrations of diuron (14MUgL(-1))
      recorded in runoff that occurred >2.5months after herbicide application in a
      1(st) ratoon crop. A cropping system employing less persistent non-selective
      herbicides and an inter-row soybean mulch resulted in no residual herbicide
      contamination in runoff water, but recorded 12.3% lower yield compared to
      Conventional practice. These findings reveal a trade-off between achieving good
      water quality with minimal herbicide contamination and maintaining farm
      profitability with good weed control.

PMID- 27046142
TI  - Effects of heavy metals and soil physicochemical properties on wetland soil
      microbial biomass and bacterial community structure.
AB  - Heavy metals (HMs) contamination is a serious environmental issue in wetland
      soil. Understanding the micro ecological characteristic of HMs polluted wetland
      soil has become a public concern. The goal of this study was to identify the
      effects of HMs and soil physicochemical properties on soil microorganisms and
      prioritize some parameters that contributed significantly to soil microbial
      biomass (SMB) and bacterial community structure. Bacterial community structure
      was analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis
      (PCR-DGGE). Relationships between soil environment and microorganisms were
      analyzed by correlation analysis and redundancy analysis (RDA). The result
      indicated relationship between SMB and HMs was weaker than SMB and
      physicochemical properties. The RDA showed all eight parameters explained 74.9%
      of the variation in the bacterial DGGE profiles. 43.4% (contain the variation
      shared by Cr, Cd, Pb and Cu) of the variation for bacteria was explained by the
      four kinds of HMs, demonstrating HMs contamination had a significant influence on
      the changes of bacterial community structure. Cr solely explained 19.4% (p<0.05)
      of the variation for bacterial community structure, and Cd explained 17.5%
      (p<0.05), indicating Cr and Cd were the major factors related to bacterial
      community structure changes.

PMID- 27046143
TI  - Computational modeling in melanoma for novel drug discovery.
AB  - INTRODUCTION: There is a growing body of evidence highlighting the applications
      of computational modeling in the field of biomedicine. It has recently been
      applied to the in silico analysis of cancer dynamics. In the era of precision
      medicine, this analysis may allow the discovery of new molecular targets useful
      for the design of novel therapies and for overcoming resistance to anticancer
      drugs. According to its molecular behavior, melanoma represents an interesting
      tumor model in which computational modeling can be applied. Melanoma is an
      aggressive tumor of the skin with a poor prognosis for patients with advanced
      disease as it is resistant to current therapeutic approaches. AREAS COVERED: This
      review discusses the basics of computational modeling in melanoma drug discovery
      and development. Discussion includes the in silico discovery of novel molecular
      drug targets, the optimization of immunotherapies and personalized medicine
      trials. EXPERT OPINION: Mathematical and computational models are gradually being
      used to help understand biomedical data produced by high-throughput analysis. The
      use of advanced computer models allowing the simulation of complex biological
      processes provides hypotheses and supports experimental design. The research in
      fighting aggressive cancers, such as melanoma, is making great strides.
      Computational models represent the key component to complement these efforts. Due
      to the combinatorial complexity of new drug discovery, a systematic approach
      based only on experimentation is not possible. Computational and mathematical
      models are necessary for bringing cancer drug discovery into the era of omics,
      big data and personalized medicine.

PMID- 27046144
TI  - A Parallel Distributed-Memory Particle Method Enables Acquisition-Rate
      Segmentation of Large Fluorescence Microscopy Images.
AB  - Modern fluorescence microscopy modalities, such as light-sheet microscopy, are
      capable of acquiring large three-dimensional images at high data rate. This
      creates a bottleneck in computational processing and analysis of the acquired
      images, as the rate of acquisition outpaces the speed of processing. Moreover,
      images can be so large that they do not fit the main memory of a single computer.
      We address both issues by developing a distributed parallel algorithm for
      segmentation of large fluorescence microscopy images. The method is based on the
      versatile Discrete Region Competition algorithm, which has previously proven
      useful in microscopy image segmentation. The present distributed implementation
      decomposes the input image into smaller sub-images that are distributed across
      multiple computers. Using network communication, the computers orchestrate the
      collectively solving of the global segmentation problem. This not only enables
      segmentation of large images (we test images of up to 10(10) pixels), but also
      accelerates segmentation to match the time scale of image acquisition. Such
      acquisition-rate image segmentation is a prerequisite for the smart microscopes
      of the future and enables online data compression and interactive experiments.

PMID- 27046145
TI  - An Alternating Current Electroosmotic Pump Based on Conical Nanopore Membranes.
AB  - Electroosmotic flow (EOF) is used to pump solutions through microfluidic devices
      and capillary electrophoresis columns. We describe here an EOF pump based on
      membrane EOF rectification, an electrokinetic phenomenon we recently described.
      EOF rectification requires membranes with asymmetrically shaped pores, and
      conical pores in a polymeric membrane were used here. We show here that solution
      flow through the membrane can be achieved by applying a symmetrical sinusoidal
      voltage waveform across the membrane. This is possible because the alternating
      current (AC) carried by ions through the pore is rectified, and we previously
      showed that rectified currents yield EOF rectification. We have investigated the
      effect of both the magnitude and frequency of the voltage waveform on flow rate
      through the membrane, and we have measured the maximum operating pressure.
      Finally, we show that operating in AC mode offers potential advantages relative
      to conventional DC-mode EOF pumps.

PMID- 27046146
TI  - Comparison of Outcomes in MRI Confirmed Lumbar Disc Herniation Patients With and
      Without Modic Changes Treated With High Velocity, Low Amplitude Spinal
      Manipulation.
AB  - OBJECTIVE: The purpose of this study was to determine if there is a difference in
      outcomes between Modic positive and negative lumbar disc herniation (LDH)
      patients treated with spinal manipulative therapy (SMT). METHODS: This
      prospective outcomes study includes 72 MRI confirmed symptomatic LDH patients
      treated with SMT. Numerical rating scale (NRS) pain and Oswestry disability data
      were collected at baseline. NRS, patient global impression of change to assess
      overall improvement, and Oswestry data were collected at 2 weeks, 1, 3, 6 months
      and 1 year. MRI scans were analyzed for Modic change present/absent and
      classified as Modic I or II when present. Chi-squared test compared the
      proportion of patients reporting relevant 'improvement' between patients with and
      without Modic changes and those with Modic I vs. II. NRS and Oswestry scores were
      compared at baseline and change scores at all follow-up time points using the
      unpaired Student t test. RESULTS: 76.5% of Modic positive patients reported
      'improvement' compared to 53.3% of Modic negative patients (P = .09) at 2 weeks.
      Modic positive patients had larger decreases in leg pain (P = .02) and disability
      scores (P = .012) at 2 weeks. Modic positive patients had larger reductions in
      disability levels at 3 (P = .049) and 6 months (P = .001). A significant
      difference (P = .001) between patients with Modic I vs. Modic II was found at 1
      year, where Modic II patients did significantly better. CONCLUSION: Modic
      positive patients reported higher levels of clinically relevant improvement 2
      weeks, 3 and 6 months compared to Modic negative patients. However, at 1 year
      Modic I patients were significantly less likely to report 'improvement',
      suggesting they may be prone to relapse.

PMID- 27046147
TI  - Evidence on the Ability of a Pneumatic Decompression Belt to Restore Spinal
      Height Following an Acute Bout of Exercise.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of a pneumatic
      decompression belt to restore spinal height lost following an acute bout of
      exercise that induced compression. METHODS: This study implemented a test-retest
      repeated measures design in which twelve participants (male = 10, female = 2)
      age, 21.5 +/- 1.0 years; height, 179.0 +/- 7.70 cm; weight, 84.0 +/-11.5 kg; were
      recruited from a university population and acted as their own control. All
      participants were healthy with no previous history of disabling back pain, and
      were frequent weight trainers. A stadiometer was used to measure spinal height at
      baseline, then following an acute bout of exercise and then again following the
      intervention (use of a pneumatic decompression belt for 20 minutes) or control
      (lying supine for 20 minutes). A 2-way repeated measures ANOVA was performed on
      the change in spinal height in order to evaluate differences between measurement
      phases and intervention conditions. RESULTS: The use of the decompression belt
      increased spinal height gain (4.3 +/- 3.0 mm) significantly more than the control
      condition (1.8 +/- 1.2 mm) following an acute bout of weightlifting exercises
      known to elicit high compressive loads on the lumbar spine. CONCLUSION: The
      pneumatic decompression belt restored spinal height faster than a non-belt
      wearing condition in young healthy asymptomatic participants.

PMID- 27046148
TI  - Factor XI Deficiency Alters the Cytokine Response and Activation of Contact
      Proteases during Polymicrobial Sepsis in Mice.
AB  - Sepsis, a systemic inflammatory response to infection, is often accompanied by
      abnormalities of blood coagulation. Prior work with a mouse model of sepsis
      induced by cecal ligation and puncture (CLP) suggested that the protease factor
      XIa contributed to disseminated intravascular coagulation (DIC) and to the
      cytokine response during sepsis. We investigated the importance of factor XI to
      cytokine and coagulation responses during the first 24 hours after CLP. Compared
      to wild type littermates, factor XI-deficient (FXI-/-) mice had a survival
      advantage after CLP, with smaller increases in plasma levels of TNF-alpha and IL
      10 and delayed IL-1beta and IL-6 responses. Plasma levels of serum amyloid P, an
      acute phase protein, were increased in wild type mice 24 hours post-CLP, but not
      in FXI-/- mice, supporting the impression of a reduced inflammatory response in
      the absence of factor XI. Surprisingly, there was little evidence of DIC in mice
      of either genotype. Plasma levels of the contact factors factor XII and
      prekallikrein were reduced in WT mice after CLP, consistent with induction of
      contact activation. However, factor XII and PK levels were not reduced in FXI-/-
      animals, indicating factor XI deficiency blunted contact activation. Intravenous
      infusion of polyphosphate into WT mice also induced changes in factor XII, but
      had much less effect in FXI deficient mice. In vitro analysis revealed that
      factor XIa activates factor XII, and that this reaction is enhanced by polyanions
      such polyphosphate and nucleic acids. These data suggest that factor XI
      deficiency confers a survival advantage in the CLP sepsis model by altering the
      cytokine response to infection and blunting activation of the contact (kallikrein
      kinin) system. The findings support the hypothesis that factor XI functions as a
      bidirectional interface between contact activation and thrombin generation,
      allowing the two processes to influence each other. 

PMID- 27046149
TI  - Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance
      Database Study.
AB  - AIMS/INTRODUCTION: This study aimed to estimate the prevalence of gestational
      diabetes mellitus (GDM) and use of anti-diabetic medications for patients with
      GDM in Korea, using data of the period 2007-2011 from the Health Insurance Review
      and Assessment (HIRA) database, which includes the claims data of 97% of the
      Korean population. MATERIALS AND METHODS: We used the Healthcare Common Procedure
      Coding System codes provided by the HIRA to identify women with delivery in the
      HIRA database between 2009 and 2011. GDM was defined according to ICD-10 codes,
      and patients with pre-existing diabetes between January 1, 2007 and pregnancy
      were excluded. A Poisson regression was performed to evaluate the trends in
      annual prevalence rates. RESULTS: The annual numbers of deliveries in 2009-2011
      were 479,160 in 2009, 449,747 in 2010, and 377,374 in 2011. The prevalence of GDM
      during that period was 7.5% in 2009-2011: 5.7% in 2009, 7.8% in 2010, and 9.5% in
      2011. The age-stratified analysis showed that the prevalence of GDM was highest
      in women aged 40-44 years, at 10.6% in 2009-2011, and that the annual prevalence
      significantly increased even in young women aged 20-29 years during that period
      (P < 0.05). More than 95% of the patients with GDM did not take any anti-diabetic
      medication. Among the anti-diabetic medications prescribed for patients with GDM,
      insulin was most commonly prescribed (for >98% of the patients with GDM on
      medication). CONCLUSIONS: The prevalence of GDM in Korean women recently reached
      5.7-9.5% in recent years. This represents a public health concern that warrants
      proper screening and medical care for GDM in women during the childbearing years.

PMID- 27046150
TI  - The pharmacology, toxicology and potential applications of arecoline: a review.
AB  - CONTEXT: Arecoline is an effective constituent of Areca catechu L. (Arecaceae)
      with various pharmacological effects. However, investigations also revealed that
      long use of arecoline could arouse some oral diseases. OBJECTIVE: The present
      review gathers the fragmented information available in the literature (before 1
      October 2015) regarding pharmacology and toxicology of arecoline. We also
      discussed the potential developments and applications of arecoline in the future.
      METHODS: All the available information regarding the arecoline is compiled from
      scientific databases, including Science Direct, PubMed, Web of Science, Scopus,
      etc. RESULTS: Previous research demonstrated that arecoline is one of the major
      effective constituents in A. catechu. Additionally, arecoline has a wide spectrum
      of pharmacological activities including effects on nervous, cardiovascular,
      digestive and endocrine systems and anti-parasitic effects. What's more,
      arecoline is reported to be the primary toxic constituent of A. catechu, and the
      main toxic effects include oral submucous fibrosis (OSF), oral squamous cell
      carcinoma (OSCC) and genotoxicity. CONCLUSION: Arecoline has great potential to
      be a therapeutic drug for various ailments. However, further investigations are
      needed in the future to reduce or eliminate its toxicities before developing into
      new drug.

PMID- 27046151
TI  - Multidirectional Angular Electronic Flux during Adiabatic Attosecond Charge
      Migration in Excited Benzene.
AB  - Recently, adiabatic attosecond charge migration (AACM) has been monitored and
      simulated for the first time, with application to the oriented iodoacetylene
      cation where AACM starts from the initial superposition of the ground state
      (phi0) and an electronic excited state (phi1). Here, we develop the theory for
      electronic fluxes during AACM in ring-shaped molecules, with application to
      oriented benzene prepared in the superposition of the ground and first excited
      singlet states. The initial state and its time evolution are analogous to
      coherent tunneling where phi0 and phi1 have different meanings; however, they
      denote the wave functions of the lowest tunneling doublet. This analogy suggests
      to transfer the theory of electronic fluxes during coherent tunneling to AACM,
      with suitable modifications which account for (i) the different time scales and
      (ii) the different electronic states, and which make use of (iii) the preparation
      of the initial state for AACM by a linearly polarized laser pulse. Application to
      benzene yields the multidirectional angular electronic flux with a pincer-motion
      type pattern during AACM: this unequivocal result confirms a previous working
      hypothesis. Moreover, the theory of AACM allows quantification of the electronic
      flux; that is, the maximum number of electrons (out of 42) which flow concertedly
      during AACM in benzene is 6 * 0.08 = 0.48. 

PMID- 27046152
TI  - Finasteride adverse effects in subjects with androgenic alopecia: A possible
      therapeutic approach according to the lateralization process of the brain.
AB  - Nowadays, finasteride is a relatively frequently prescribed drug in the
      therapeutic management of male androgenic alopecia. The reported adverse effects
      are notable in some patients, consisting in signs and symptoms that are
      encountered both during finasteride administration and after treatment cessation.
      Clinical and imagistic data show that cognition and sexuality are two distinct
      but interrelated environmental functions, most probable due to lateralization
      process of the brain. Specific for our topic, relatively recent published studies
      found that frequency and severity of finasteride adverse effects could be
      interrelated with hand preference and sexual orientation of the respective
      subjects. This paper tries to explain/support this interrelation through a
      psychophysiologic approach, to suggest how this premise could be further proved
      in dermatological practice, and to highlight its relevance in respect to
      therapeutic approach of male androgenic alopecia. As a possible therapeutic
      application, subjects having preference for a certain sexual orientation and/or
      predisposition for a given dominant hand could be advised before finasteride
      administration, that present an increased risk/sensitivity to develop adverse
      effects. Finally, even if finasteride and post-finasteride symptoms overlap to a
      large extent they should be, however, viewed as distinct physiopathologic
      entities, which could require perhaps different therapeutic approaches.

PMID- 27046153
TI  - Risk of Bias in Systematic Reviews of Non-Randomized Studies of Adverse
      Cardiovascular Effects of Thiazolidinediones and Cyclooxygenase-2 Inhibitors:
      Application of a New Cochrane Risk of Bias Tool.
AB  - BACKGROUND: Systematic reviews of the effects of healthcare interventions
      frequently include non-randomized studies. These are subject to confounding and a
      range of other biases that are seldom considered in detail when synthesizing and
      interpreting the results. Our aims were to assess the reliability and usability
      of a new Cochrane risk of bias (RoB) tool for non-randomized studies of
      interventions and to determine whether restricting analysis to studies with low
      or moderate RoB made a material difference to the results of the reviews. METHODS
      AND FINDINGS: We selected two systematic reviews of population-based, controlled
      non-randomized studies of the relationship between the use of thiazolidinediones
      (TZDs) and cyclooxygenase-2 (COX-2) inhibitors and major cardiovascular events.
      Two epidemiologists applied the Cochrane RoB tool and made assessments across the
      seven specified domains of bias for each of 37 component studies. Inter-rater
      agreement was measured using the weighted Kappa statistic. We grouped studies
      according to overall RoB and performed statistical pooling for (a) all studies
      and (b) only studies with low or moderate RoB. Kappa scores across the seven bias
      domains ranged from 0.50 to 1.0. In the COX-2 inhibitor review, two studies had
      low overall RoB, 14 had moderate RoB, and five had serious RoB. In the TZD
      review, six studies had low RoB, four had moderate RoB, four had serious RoB, and
      two had critical RoB. The pooled odds ratios for myocardial infarction, heart
      failure, and death for rosiglitazone versus pioglitazone remained significantly
      elevated when analyses were confined to studies with low or moderate RoB.
      However, the estimate for myocardial infarction declined from 1.14 (95% CI 1.07
      1.24) to 1.06 (95% CI 0.99-1.13) when analysis was confined to studies with low
      RoB. Estimates of pooled relative risks of cardiovascular events with COX-2
      inhibitors compared with no nonsteroidal anti-inflammatory drug changed little
      when analyses were confined to studies with low or moderate RoB. The exception
      was a rise in the relative risk associated with ibuprofen from 1.07 (95% CI 0.97
      1.18) to 1.14 (95% CI 1.03-1.26). The main limitation of our study was testing
      the instrument on a narrow range of pharmacoepidemiological studies; we cannot
      assume our findings extend to a broader range of interventions and settings.
      CONCLUSIONS: The Cochrane RoB tool highlighted a wide range of risks of bias in
      studies included in two widely cited reviews and had the potential to change the
      conclusions of the reviews. Systematic reviews that incorporate non-randomized
      studies of medical interventions should include a detailed assessment of RoB for
      each included study.

PMID- 27046154
TI  - Dynamics of the Developing Chick Chorioallantoic Membrane Assessed by Stereology,
      Allometry, Immunohistochemistry and Molecular Analysis.
AB  - The chick chorioallantoic membrane (CAM) is a widely used model for the study of
      angiogenesis, tumour growth, as well as drug efficacy. In spite of this, little
      is known about the developmental alteration from its appearance to the time of
      hatching. In the current study the CAM has been studied by classical stereology
      and allometry. Expression levels of selected angiogenesis-related molecules were
      estimated by RT-PCR and cell dynamics assessed by proliferation and apoptosis
      assays. Absolute CAM volume increased from a low of 0.47 +/- 0.11 cm3 at
      embryonic day 8 (E8) to a high of 2.05 +/- 0.27 cm3 at E18, and then decreased to
      1.6 +/- 0.47 cm3 at E20. On allometric analysis, three growth phases were
      identifiable. Between E8-13 (phase I), the CAM grew fastest; moderately in phase
      II (E13-18) but was regressing in phase III (E18-20). The chorion, the mesenchyme
      and the allantoic layers grew fastest in phase I, but moderately in phase II. The
      mesenchyme grew slowly in phase III while the chorion and allantois were
      regressing. Chorionic cell volume increased fastest in phase I and was regressing
      in phase III. Chorionic capillaries grew steadily in phase I and II but regressed
      in phase III. Both the chorion and the allantois grew by intrinsic cell
      proliferation as well as recruitment of cells from the mesenchyme. Cell
      proliferation was prominent in the allantois and chorion early during
      development, declined after E17 and apoptosis started mainly in the chorion from
      E14. VEGFR2 expression peaked at E11 and declined steadily towards E20, VEGF
      peaked at E13 and E20 while HIF 1alpha had a peak at E11 and E20. Studies
      targeting CAM growth and angiogenesis need to take these growth phases into
      consideration. 

PMID- 27046155
TI  - Rapid investigation of cases and clusters of Legionnaires' disease in England and
      Wales using direct molecular typing.
AB  - Legionella pneumophila is the leading cause of Legionnaires' disease, a severe
      pneumonia that can occur as sporadic cases or point-source outbreaks affecting
      multiple patients. The infection is acquired by inhalation of aerosols from
      contaminated water systems. In order to identify the probable source and prevent
      further cases, clinical and environmental isolates are compared using phenotypic
      and genotypic methods. Typically up to 10 days are required to isolate L.
      pneumophila prior to the application of standard typing protocols. A rapid
      protocol using a real-time PCR specific for L. pneumophila and serogroup 1,
      combined with nested direct molecular typing, was adopted by Public Health
      England in 2012 to reduce reporting time for preliminary typing results. This
      rapid protocol was first used to investigate an outbreak that occurred in
      July/August 2012 and due to the positive feedback from that investigation, it was
      subsequently applied to other incidents in England and Wales where faster typing
      results would have aided incident investigation. We present here results from
      seven incidents that occurred between July 2012 and June 2015 where the use of
      this rapid approach provided preliminary characterization of the infecting strain
      in an average 1.58 days (SD 1.01) after sample receipt in contrast to 9.53 days
      (SD 3.73) when standard protocols were applied. 

PMID- 27046156
TI  - Association of increased monetary cost of dietary intake, diet quality and weight
      management in Spanish adults - CORRIGENDUM.

PMID- 27046157
TI  - Targeted tumor delivery and controlled release of neuronal drugs with ferritin
      nanoparticles to regulate pancreatic cancer progression.
AB  - Pancreatic cancer is a lethal malignancy whose progression is highly dependent on
      the nervous microenvironment. This study develops neural drug-loaded ferritin
      nanoparticles (Ft NPs) to regulate the nervous microenvironment, in order to
      control the pancreatic cancer progression. The drug-loaded Ft NPs can target
      pancreatic tumors via passive targeting of EPR effects of tumors and active
      targeting via transferrin receptor 1 (TfR1) binding on cancer cells, with a
      triggered drug release in acidic tumor environment. Two drugs, one activates
      neural activity (carbachol), the other impairs neural activity (atropine), are
      encapsulated into the Ft NPs to form two kinds of nano drugs, Nano-Cab NPs and
      Nano-Ato NPs, respectively. The activation of the nervous microenvironment by
      Nano-Cab NPs significantly promotes the pancreatic tumor progression, whereas the
      blockage of neural niche by Nano-Ato NPs remarkably impairs the neurogenesis in
      tumors and the progression of pancreatic cancer. The Ft-based nanoparticles thus
      comprise an effective and safe route of delivery of neural drugs for novel anti
      cancer therapy.

PMID- 27046158
TI  - Combined approaches of EPR and NMR illustrate only one transmembrane helix in the
      human IFITM3.
AB  - Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry
      of a wide spectrum of viruses to the cytosol of the host. The mechanism used by
      the protein to restrict viral entry is unclear given the unavailability of the
      membrane topology and structures of the IFITM family proteins. Systematic site
      directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies
      of IFITM3 in detergent micelles identified a single, long transmembrane helix in
      the C-terminus and an intramembrane segment in the N-terminal hydrophobic region.
      Solution NMR studies of the same sample verified the secondary structure
      distribution and demonstrated two rigid regions interacting with the micellar
      surface. The resulting membrane topology of IFITM3 supports the mechanism of an
      enhanced restricted membrane hemi-fusion. 

PMID- 27046159
TI  - DAPT Score Utility for Risk Prediction in Patients With or Without Previous
      Myocardial Infarction.
AB  - BACKGROUND: The DAPT (Dual Antiplatelet Therapy) study enrolled patients after
      coronary stenting. Patients randomized to continued thienopyridine and aspirin
      after 12 months had lower ischemic risk but higher bleeding risk than those
      treated with placebo and aspirin. OBJECTIVES: This study sought to determine
      whether a decision tool (DAPT score) aids prescription of dual antiplatelet
      therapy duration in patients with or without prior myocardial infarction (MI)
      treated with coronary stents. METHODS: Patients were categorized according to any
      history of MI before the index procedure or no history of MI. Risk differences
      during the randomized treatment period (12 to 30 months) for ischemic (MI and/or
      stent thrombosis) and bleeding (Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Arteries moderate/severe) events were compared
      according to DAPT score. RESULTS: Rates of MI were 3.8% versus 2.4% (p = 0.01)
      for patients with any MI versus no MI. Continued thienopyridine reduced late MI
      compared with placebo regardless of MI history (hazard ratio [HR] for any MI:
      0.46; p < 0.001; HR for no MI: 0.60; p = 0.003) and increased bleeding (HR: 1.86,
      p = 0.01 any MI; HR: 1.58, p = 0.01 no MI). DAPT scores >=2 were associated with
      reductions in MI/stent thrombosis with continued thienopyridine compared with
      placebo (2.7% vs. 6.0%, p < 0.001 any MI; 2.6% vs. 5.2%, p = 0.002 no MI), with
      comparable bleeding rates. Among patients with DAPT scores <2 in both groups,
      continued thienopyridine was associated with significantly increased bleeding but
      similar rates of ischemia. CONCLUSIONS: Patients with previous MI have greater
      risk of late ischemic events than those with no MI history. The DAPT score
      improves prediction of patient benefit and harm from continued dual antiplatelet
      therapy beyond assessment of MI history alone. (The Dual Antiplatelet Therapy
      Study; NCT00977938).

PMID- 27046160
TI  - Reduction in Ischemic Events With Ticagrelor in Diabetic Patients With Prior
      Myocardial Infarction in PEGASUS-TIMI 54.
AB  - BACKGROUND: Patients with diabetes appear to be at elevated risk of
      atherothrombotic events. OBJECTIVES: The purpose of this study was to determine
      the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events
      in patients with diabetes and prior myocardial infarction (MI). METHODS: We
      examined the subgroups of patients with diabetes (n = 6,806) and without diabetes
      (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in
      Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a
      Background of Aspirin-Thrombolysis In Myocardial Infarction 54), in which 21,162
      patients with a history of MI 1 to 3 years prior and with additional risk factors
      were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were
      followed for a median of 33 months. The primary efficacy endpoint was major
      adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the
      primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major
      bleeding. RESULTS: The relative risk reduction in MACE with ticagrelor was
      consistent for the pooled doses versus placebo in patients with diabetes (hazard
      ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and
      without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction =
      0.99). As patients with diabetes were at higher risk of MACE, the absolute risk
      reduction tended to be greater in patients with versus without diabetes (1.5% vs.
      1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients
      with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk
      reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in
      patients with diabetes, ticagrelor reduced cardiovascular death by 22% and
      coronary heart disease death by 34%. Similar to patients without diabetes, there
      was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI:
      1.52 to 4.33; p = 0.0004). CONCLUSIONS: In patients with diabetes with prior MI,
      adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic
      events, including cardiovascular and coronary heart disease death. (Prevention of
      Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor
      Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

PMID- 27046161
TI  - 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies
      for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular
      Disease Risk: A Report of the American College of Cardiology Task Force on
      Clinical Expert Consensus Documents.

PMID- 27046164
TI  - Vacuum-Ultraviolet Promoted Oxidative Micro Photoetching of Graphene Oxide.
AB  - Microprocessing of graphene oxide (GO) films is of fundamental importance in
      fabricating graphene-based devices. We demonstrate the photoetching of GO sheets
      using vacuum-ultraviolet (VUV, lambda = 172 nm) light under controlled
      atmospheric pressure. X-ray photoelectron spectroscopy (XPS), atomic force
      microscopy (AFM) and differential interference contrast microscopy (DIC) studies
      revealed that the photoetching of GO films successfully proceeded in the regions
      exposed to VUV irradiation in the oxygen-containing atmosphere. Precise
      photoetching of the GO sheets was achieved at a vacuum pressure of 5 * 10(3) Pa
      with VUV light irradiation for 20 min. This was followed by VUV irradiation in a
      high vacuum (<10(-3) Pa) and sonication in water. The photoetched GO sheets then
      transformed into reduced GO (rGO) patterns. The minimum feature fabricated by
      this method was 2 MUm wide lines aligned at an interval of 4 MUm. This method
      provides a cost-effective way to fabricate rGO patterns with fewer boundaries
      between rGO sheets and offers a better integrity of rGO, which can be promising
      for further applications in micro mechanics, micro electrochemistry,
      optoelectronics, etc.

PMID- 27046162
TI  - Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in
      Patients With Peripheral Artery Disease.
AB  - BACKGROUND: Peripheral artery disease (PAD) is associated with heightened
      ischemic and bleeding risk in patients with prior myocardial infarction (MI).
      OBJECTIVES: This study evaluated the efficacy and safety of ticagrelor on major
      cardiovascular (CV) events and major adverse limb events in patients with PAD and
      a prior MI. METHODS: PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in
      Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a
      Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162
      patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor
      60 mg twice daily, or placebo, all on a background of low-dose aspirin. History
      of PAD was obtained at baseline. Occurrences of major adverse cardiovascular
      events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events
      (MALE) (defined as acute limb ischemia or peripheral revascularization for
      ischemia) were recorded in follow-up. RESULTS: A total of 1,143 patients (5%) had
      known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE
      at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which
      persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60;
      95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute
      limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15%
      vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was
      consistent, regardless of PAD, patients with PAD had a greater absolute risk
      reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk.
      The absolute excess of TIMI major bleeding was 0.12% (number needed to harm:
      834). The 60-mg dose had particularly favorable outcomes for CV and all-cause
      mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio:
      0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). CONCLUSIONS: Among
      stable patients with prior MI, those with concomitant PAD have heightened
      ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute
      risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With
      Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of
      Aspirin [PEGASUS-TIMI 54]; NCT01225562).

PMID- 27046163
TI  - The evolving world of small RNAs from RNA viruses.
AB  - RNA virus infection in plants and invertebrates can produce virus-derived small
      RNAs. These RNAs share features with host endogenous small interfering RNAs
      (siRNAs). They can potentially mediate RNA interference (RNAi) and related RNA
      silencing pathways, resulting in specific antiviral defense. Although most RNA
      silencing components such as Dicer, Ago2, and RISC are conserved among eukaryotic
      hosts, whether RNA virus infection in mammals can generate functional small RNAs
      that act in antiviral defense remains under discussion. Here, we review recent
      studies on the molecular and biochemical features of viral siRNAs and other virus
      derived small RNAs from infected plants, arthropods, nematodes, and vertebrates
      and discuss the genetic pathways for their biogenesis and their roles in
      antiviral activity. WIREs RNA 2016, 7:575-588. doi: 10.1002/wrna.1351 For further
      resources related to this article, please visit the WIREs website.

PMID- 27046166
TI  - Stability and change in callous-unemotional traits: Longitudinal associations
      with potential individual and contextual risk and protective factors.
AB  - This longitudinal study examines developmental heterogeneity in callous
      unemotional (CU) traits in a large sample of school-age children in Cyprus.
      Latent Class Growth Analysis revealed 4 trajectory groups of CU traits across 3
      time points: stable high, increasing, decreasing, and low. Findings suggested
      that children in the stable high CU trajectory were more likely to (a) exhibit
      high and stable levels of conduct problems, attention-deficit/hyperactivity
      disorder symptoms, impulsivity and narcissism, (b) experience low parental
      involvement and high parental distress, (c) report low peer support and school
      connectedness, and (d) score lower on academic performance, executive
      functioning, social competence, and self-regulation compared to children with
      low, decreasing, and increasing CU traits. These findings were verified by both
      parent and child reports. Repeated analysis of variance suggested that increases
      and decreases in CU traits were associated with similar changes in conduct
      problems, narcissism, impulsivity, and maternal involvement. Further, children in
      the decreasing trajectory group were not differentiated from children in the low
      risk group on measures of executive functioning, academic performance, school
      connectedness, and peer social support at the last wave of measurement. These
      findings provide evidence for the importance of taking longitudinal change into
      account for understanding developmental heterogeneity in CU traits and the
      association of these traits with possible protective (e.g., stable high maternal
      involvement) and risk (e.g., decreases in maternal involvement and increases in
      conduct problems, impulsivity and narcissism) variables. (PsycINFO Database
      Record

PMID- 27046165
TI  - Substance Use and Depression Symptomatology: Measurement Invariance of the Beck
      Depression Inventory (BDI-II) among Non-Users and Frequent-Users of Alcohol,
      Nicotine and Cannabis.
AB  - Depression is a highly heterogeneous condition, and identifying how symptoms
      present in various groups may greatly increase our understanding of its etiology.
      Importantly, Major Depressive Disorder is strongly linked with Substance Use
      Disorders, which may ameliorate or exacerbate specific depression symptoms. It is
      therefore quite plausible that depression may present with different symptom
      profiles depending on an individual's substance use status. Given these
      observations, it is important to examine the underlying construct of depression
      in groups of substance users compared to non-users. In this study we use a non
      clinical sample to examine the measurement structure of the Beck Depression
      Inventory (BDI-II) in non-users and frequent-users of various substances.
      Specifically, measurement invariance was examined across those who do vs. do not
      use alcohol, nicotine, and cannabis. Results indicate strict factorial invariance
      across non-users and frequent-users of alcohol and cannabis, and metric
      invariance across non-users and frequent-users of nicotine. This implies that the
      factor structure of the BDI-II is similar across all substance use groups. 

PMID- 27046167
TI  - Micropapillary: A component more likely to harbour heterogeneous EGFR mutations
      in lung adenocarcinomas.
AB  - The micropapillary (MP) subtype has recently been established to be a distinct
      marker of poor prognosis in lung adenocarcinomas (LACs). According to the 2015
      WHO classification system, LAC constituents are required to be precisely
      reported. T790M mutation and an insertion in exon 20 (E20ins) are associated with
      EGFR-TKI resistance. A total of 211 LAC patients were involved in this study, and
      EGFR mutations were determined using an amplification refractory mutation system
      (ARMS). Sex, smoking history, lymph node status, and clinical stage differed
      significantly between the EGFR wild type and mutant groups (p < 0.05). The EGFR
      mutation occurred more frequently in female, non-smokers, ACs with papillary
      (85.7%) or MP components (91.4%) (p < 0.001). Twenty ACs with naive T790M or
      E20ins were microdissected. The AC constituents metastasizing to lymph nodes
      exhibited a phenotype and EGFR status that was consistent with the primary loci
      constituents. Glomerulus-like solid components exhibited the same EGFR status as
      the surrounding T790M-mutated MP components. The MP and glomerulus-like portions
      in AC tumours exhibited a congenial EGFR status, but the acinar cells with
      papillary cells were heterogeneous. The naive T790M mutants, although minor in
      the MP component, dramatically increased after EGFR-TKI therapy and indicate that
      the MP components feature intrinsic heterogeneity. 

PMID- 27046169
TI  - Correction: An Endophytic Fungus, Talaromyces radicus, Isolated from Catharanthus
      roseus, Produces Vincristine and Vinblastine, Which Induce Apoptotic Cell Death.

PMID- 27046168
TI  - Multispecific Organic Cation Transporter 1 (OCT1) from Bos taurus Has High
      Affinity and Slow Binding Kinetics towards Prostaglandin E2.
AB  - Organic cation transporter 1 (OCT1, SLC22A1), like many solute carrier 22 (SLC22)
      family members, is important for the disposition of clinically important drugs,
      metabolites and signaling molecules. Several studies suggest that SLC22 family
      (eg. organic anion transporters or OATs and OCTs) bind and possibly transport
      prostaglandins with relatively high affinity (submicromolar). The affinities of
      OCT1 and OATs toward PGE2 and PGF2a reported in these cell-based transport
      studies are considerably greater than for xenobiotics and natural metabolite
      substrates--in many cases over 100-fold higher. This raises the possibility that
      prostaglandins are key endogenous substrates and/or that they act on the
      transporter in a manner different from other substrates such as xenobiotics and
      lower affinity metabolites. To further investigate OCT1-prostaglandin
      interactions, we designed biophysical studies using purified bovine OCT1 (Bos
      taurus, btOCT1/SLC22A1) with PGE2 analogs, in fluorescently labeled and label
      free formats. Using fluorescence polarization (FP), we detected a binding of
      btOCT1 to the PGE2-Rhodamine conjugate at submicromolar affinity, consistent with
      affinity data for PGE2 from cells over-expressing the related human OCT1. Using
      purified native btOCT1 as analyte and biotinylated PGE2 analog as ligand, our
      data from surface plasmon resonance (SPR) revealed that btOCT1 specifically
      interacts to PGE2 with KD values in the hundred nanomolar range. BtOCT1 also
      demonstrated a slow association (ka) in the range of 103 M(-1) s(-1) and an even
      slower dissociation rate (kd) in the range of 10-4 s(-1) for PGE2, suggesting the
      possibility of a different mode of binding compared to other structurally
      unrelated transported substrates of low-affinity (eg. drugs, metabolites). Our
      results complement in vitro transport studies and provide direct evidence that
      OCT1--which is normally expressed in liver and other tissues--interacts with
      prostaglandin analogs. While it is not entirely clear from the published
      literature whether OCTs function as major prostaglandin transporters, the tight
      binding of the naturally occurring PGE2, as well as the slow dissociation rate,
      could conceivably affect the transport of lower affinity substrates such as drugs
      and metabolites by SLC22 transporters. More research is necessary to establish
      the extent to which individual SLC22 family members actually function as PG
      transporters in vitro and in vivo and to investigate whether PGs can, independent
      of being directly transported, alter the ability of SLC22 transporters to handle
      drugs and other substrates.

PMID- 27046170
TI  - Priorities for Research to Reduce the Threat of Firearm-Related Violence.

PMID- 27046171
TI  - U.S. Medical Support in a Developing World Health System - a Partnership Made in
      Africa for a "New Normal" Strategy.

PMID- 27046172
TI  - Why We Vaccinate Sailors.

PMID- 27046173
TI  - Two-Year-Old Boy With Painless Hematuria.

PMID- 27046174
TI  - Economic Burden of Hearing Loss for the U.S. Military: A Proposed Framework for
      Estimation.
AB  - The goal of this multiphased research is to develop methods to comprehensively
      determine the economic impact of hearing impairment and noise-induced hearing
      injury among active duty U.S. Service Members. Several steps were undertaken to
      develop a framework and model for economic burden analysis: (1) a literature
      review identifying studies reporting the cost of health conditions and injuries
      in the Department of Defense, (2) consultation with a panel of subject matter
      experts who reviewed these cost items, and (3) discussions with DoD data stewards
      and review of relevant data dictionaries and databases. A Markov model was
      developed to represent the cumulative economic effect of events along the career
      span, such as retraining after hearing impairment and injury, by synthesizing
      inputs from various sources. The model, as developed and proposed in this study,
      will be a valuable decision-making tool for the DoD to identify high-risk groups,
      take proactive measures, and develop focused education, customized equipping, and
      return-to-duty and reintegration programs, thereby maximizing the retention of
      skilled, experienced, and mission-ready Service Members. 

PMID- 27046175
TI  - Findings From the Department of Veterans Affairs Qarmat Ali Medical Surveillance
      Program.
AB  - OBJECTIVE: To review the Veterans Affairs (VA) medical surveillance program for
      Veterans with potential hexavalent chromium (CrVI) exposure that occurred during
      2003. METHODS: Retrospective review of medical records of the 124 Veterans that
      participated in standardized, in-person clinical evaluations for possible CrVI
      exposure during the incident in question. The evaluations were reviewed to define
      population level effects. In addition, a mortality analysis was conducted for the
      808 unique personal identifiers available to Veterans Health Administration.
      RESULTS: Mean reported number of days exposed was 21 (median 10). A history of
      respiratory (n = 78) and skin (n = 38) symptoms were reported during the period
      of exposure. No abnormalities that were specific to chromium exposure (e.g.,
      nasal septum perforation) were found. Eight deaths occurred between 2005 and
      2012. CONCLUSIONS: The lack of severe nasal abnormalities in the VA evaluations
      supports a time-limited peak exposure. However, the overall low participation
      rate (15%) severely compromises any ability to generalize to the entire
      potentially exposed population. Regardless, since the actual level of exposure to
      CrVI will never be known with certainty, the VA will continue to monitor these
      Veterans with periodic evaluations to identify and manage any pathologic findings
      that might be associated with past CrVI exposure.

PMID- 27046176
TI  - Preventing Exertional Death in Military Trainees: Recommendations and Treatment
      Algorithms From a Multidisciplinary Working Group.
AB  - Despite aggressive prevention programs and strategies, nontraumatic exertional
      sudden death events in military training continue to prove a difficult challenge
      for the Department of Defense. In November 2014, the 559th Medical Group at Joint
      Base San Antonio-Lackland, Texas, hosted a working group on sudden exertional
      death in military training. Their objectives were three-fold: (1) determine best
      practices to prevent sudden exertional death of military trainees, (2) determine
      best practices to establish safe and ethical training environments for military
      trainees with sickle cell trait, and (3) develop field-ready algorithms for
      managing military trainees who collapse during exertion. This article summarizes
      the major findings and recommendations of the working group. 

PMID- 27046177
TI  - Effect of Multiple Deployments on Military Families: A Cross-Sectional Study of
      Health and Well-Being of Partners and Children.
AB  - This study explored the impact of multiple deployments on the health and well
      being of the partners (married or de facto) and children of Australian military
      personnel who have deployed frequently. Permission to contact military partners
      was sought from a sample of Australian Defence Force (ADF) members. Partners
      provided data on deployment history, physical health, mental health, and their
      children's emotions, and behaviors. Associations between multiple deployments and
      health and well-being of partners and children were assessed using logistic
      regression. Data were collected from 1,332 Australian Defence Force partners
      (response rate 36%) with 1,095 children aged between 4 and 17 years. Almost half
      (47%) of partners had experienced more than one deployment, mainly to Timor
      Leste, Iraq, and Afghanistan. There was little evidence of associations between
      numbers of deployments and the health of the partner. In contrast, more
      behavioral problems were reported for children who experienced two or more
      deployments with odds ratios generally greater than 2 and significant trends with
      increasing numbers of deployment. Although military families who experience
      multiple deployments may, by selection, be more resilient than those who have
      fewer deployments, these results suggest that adverse impacts on the children may
      accrue with increasing parental absences because of deployment. 

PMID- 27046178
TI  - Lived Experience of the Warrior Nurse as an Advisor.
AB  - PURPOSE: Described the lived experience of U.S. warrior nurses who served as
      advisors to host nation officials in Afghanistan. METHOD: The phenomenological
      approach was applied to obtain comprehensive descriptions from 10 warrior nurses.
      The modified Stevick-Colaizzi-Keen data analysis method was utilized as the
      researcher had performed in the role of interest. DISCUSSION: Textural themes
      included (a) challenging role, (b) challenging place, and (c) changed. One of two
      structural themes representing the core traits included four subthemes (a) be
      careful, (b) be powerful, (c) be courageous, and (d) be resourceful. The other
      structural theme representing the skin or outer traits included four subthemes
      (a) be impeccable, (b) be malleable, (c) be caring, and (d) be resilient.
      CONCLUSION: The findings provided validation of previous information and new
      insight for nursing and military professions in terms of advancement of the
      practice of military nursing and enhancing the understanding of personnel who
      participate in the complexities of health care transformation. The need to apply
      the information gained in this study to enhance role player preparations and
      support was confirmed.

PMID- 27046179
TI  - Predictors of Positive Illicit Drug Tests After OEF/OIF Deployment Among Army
      Enlisted Service Members.
AB  - OBJECTIVE: To identify characteristics associated with testing positive for
      illicit drugs postdeployment among Army enlisted members. METHODS: Army active
      duty and National Guard/Reserve enlisted members returning from Operation
      Enduring Freedom/Operation Iraqi Freedom deployments in fiscal years 2008 to
      2011, who submitted urine specimens for random and other illicit drug tests up to
      3 years postdeployment, were included. Multiple logistic regression models,
      stratified by component, identified demographic and deployment characteristics
      associated with any positive drug test (cocaine, heroin, tetrahydrocannabinol
      [marijuana], or amphetamine) during the 3 years postdeployment. RESULTS: Among
      Army active duty and National Guard/Reserve enlisted members, respectively, 3.46%
      (95% confidence interval 3.40-3.52) and 3.84% (confidence interval 3.74-3.94)
      tested positive for 1+ illicit drugs during the 3 years postdeployment; the vast
      majority for marijuana. Relative to other groups, increased odds of a positive
      drug test were found for members with a combat specialist occupation, or first
      deployers. CONCLUSION: Almost 4% of Army members tested positive for illicit drug
      use within 3 years of return from deployment. Early identification and
      intervention with enlisted members who are more likely to test positive for
      illicit drug use should be explored to see if it will enhance health and reduce
      illegal drug use after deployment to a war zone.

PMID- 27046180
TI  - Self-Directed Violence Aboard U.S. Navy Aircraft Carriers: An Examination of
      General and Shipboard-Specific Risk and Protective Factors.
AB  - Self-directed violence (SDV), which includes suicidal ideation with and without
      intent, suicidal preparatory behaviors and attempts with and without harm, non
      suicidal self-directed violence, and completed suicide, has been a rising concern
      in the military. Military shipboard personnel may represent a unique subset of
      this population due to the distinct nature of deployment stressors and embedded
      supports. As such, one might expect differences in the prevalence of SDV between
      this group and other active duty personnel, signifying a distinct operational
      impact. This study analyzed the prevalence of SDV among personnel assigned or
      deployed to U.S. Navy aircraft carriers, and examined whether occurrences varied
      by descriptors commonly identified in the literature (e.g., age, gender, marital
      status, pay grade/rank). This study also examined characteristics specific to
      life aboard a U.S. Navy aircraft carrier in order to better understand the issues
      particular to this population. Descriptive analyses and relative risk findings
      suggested similarities in demographic risk factors to the general military
      population, but also striking differences related to occupational specialty and
      assigned department. This study is the first to shed light on risk and protective
      factors relevant to shipboard personnel. 

PMID- 27046181
TI  - Online Reporting of Military Sexual Trauma.
AB  - Case finding and treatment of military sexual trauma (MST) remains a serious
      problem in military and veteran populations as well as in the civilian
      population. This report provides descriptive examples, with statistics, of
      persons serving in the military or while living/working on a military base when
      they experienced unwanted sex. Males, more than females, never disclosed MST
      before online survey, had more physical injuries as a result and reported chronic
      disturbing thoughts of the experience. Undisclosed and unreported intrafamilial
      childhood sexual experiences were cited before an MST by some respondents.
      Interprofessional collaboration is recommended between military nurse
      practitioners and behavioral health clinicians as well as innovative strategies
      using telecommunication and online counseling. 

PMID- 27046182
TI  - Patients Provide Recommendations for Improving Patient Satisfaction.
AB  - National Committee for Quality Assurance recommends patient-centered medical
      homes incorporate input from patient populations; however, many health care
      organizations do not. This qualitative study used two open-ended questions from
      148 active duty Army Soldiers and their family members to illicit recommendations
      for primary care providers and clinic leadership that would improve their health
      care experiences. Content analysis and descriptive statistics were used to
      analyze responses. Participant responses were related to four major themes:
      Access to Care, Interpersonal Interaction, Satisfaction of Care, and Quality of
      Care. Participants were overall satisfied with their care; however, spending less
      time waiting for appointments and to see the provider or specialist were the most
      frequently requested improvements related to Access to Care. For Interpersonal
      Interaction, 82% of the responses recommended that providers be more attentive
      listeners, courteous, patient, caring, and respectful. Decreasing wait times and
      improving interpersonal skills would improve health care experiences and patient
      satisfaction. 

PMID- 27046183
TI  - Intra-Weekly Variations of Influenza-Like Illness in Military Populations.
AB  - In this report, we describe and analyze a periodic pattern in influenza-like
      illness within active military populations, derived from the Defense Medical
      Surveillance System data set. We find that there is a well-defined pattern with
      peak incidence on Monday, decaying to Friday, and remaining roughly constant over
      the weekend. Moreover, we find that the pattern systematically changes in
      response to public holidays. We quantitatively describe the effect of this
      modulation, and show how these results may be used to detrend military and, by
      extension, civilian data sets. As medical data streams become more timely, these
      results may be used to infer near-real-time daily estimates of influenza-like
      illness incidence, which may form the basis of a forecasting tool for imminent
      outbreaks. 

PMID- 27046184
TI  - Prevalence of Cardiac Arrhythmia Under Stress Conditions in Occupational Health
      Assessments of Young Military Servicemen and Servicewomen.
AB  - OBJECTIVES: In health assessments of young temporary-career volunteers who are up
      for re-enlistment, cardiac stress tests are mandatory to detect cardiac diseases
      and to confirm physical fitness. So far, there is no information available
      regarding the extent to which this time-consuming examination contributes to the
      diagnosis of pathological cardiac arrhythmia in this young, preselected patient
      collective. METHODS: In a retrospective data analysis, health assessments of 1919
      temporary-career volunteers conducted between 2007 and 2012 were examined with
      regard to pathological findings provided by resting electrocardiograms (ECGs) and
      exercise ECGs. RESULTS: Only five subjects showed signs of heart disease during
      the resting ECG; none of the exercise ECGs revealed any abnormalities, even after
      further cardiological examinations. CONCLUSIONS: In health assessments of young
      temporary-career volunteers, the exercise ECG as a mandatory examination should
      be replaced by the resting ECG. In addition to avoiding unnecessary examinations
      and associated risks, quite a large number of working years could be saved both
      for medical personnel and the persons examined.

PMID- 27046185
TI  - "Let Me Get You a Nicotine Patch": Nurses' Perceptions of Implementing Smoking
      Cessation Guidelines for Hospitalized Veterans.
AB  - Many hospitalized smokers do not receive guideline-recommended tobacco treatment,
      but little is known about the perceptions of inpatient nurses with regard to
      tobacco treatment. We used a sequential explanatory mixed methods design to help
      explain the findings of an academic detailing intervention trial on the inpatient
      medicine units of four Veterans Affairs (VA) hospitals. We surveyed 164 nurses
      and conducted semistructured interviews in a purposeful sample of 33 nurses with
      different attitudes toward cessation counseling. Content analysis was used to
      inductively characterize the issues raised by participants. Emerging themes were
      categorized using the knowledge-attitudes-behavior framework of guideline
      adherence. Knowledge-related and attitudinal barriers included perceived lack of
      skills in cessation counseling and skepticism about the effectiveness of
      cessation guidelines in hospitalized veterans. Nurses also reported multiple
      behavioral and organizational barriers to guideline adherence: resistance from
      patients, insufficient time and resources, the presence of smoking areas on VA
      premises, and lack of coordination with primary care. VA hospitals should train
      inpatient staff how to negotiate behavior change, integrate cessation counseling
      into nurses' workflow, develop alternative referral mechanisms for post-discharge
      cessation counseling, and adopt hospital policies to promote inpatient
      abstinence. 

PMID- 27046186
TI  - Comparative Resuscitative Methods for Venlafaxine Toxicity in a Swine Model.
AB  - OBJECTIVES: Venlafaxine overdose can lead to cardiovascular collapse that is
      difficult to resuscitate with traditional Advanced Cardiovascular Life Support
      protocols. Evidence has suggested that lipid emulsion infusion therapy has been
      successful in the treatment of antidepressant overdose. No studies have
      determined the optimal combination of lipid/advanced cardiovascular life support
      therapy for treatment. METHODS: This study was a prospective, experimental,
      between subjects design with a swine model investigating the effectiveness of
      drug combinations administered with cardiopulmonary resuscitation (CPR)
      postvenlafexine overdose. Subjects were randomly assigned to 1 of eight groups
      containing seven subjects. The groups tested were CPR only and CPR with
      epinephrine alone; vasopressin alone; lipid alone; epinephrine and vasopressin;
      epinephrine and lipid; vasopressin and lipid; and epinephrine, vasopressin, and
      lipid. The outcomes of interest were survival odds and time to return of
      spontaneous circulation. RESULTS: Results on these swine models indicate that the
      use of vasopressin coupled with lipids for venlafaxine overdose resulted in a
      higher survival rate when compared to the control group (p = 0.023). Groups
      receiving vasopressin experienced statistically faster times to return of
      spontaneous circulation than other groups (p = 0.019). CONCLUSIONS: The results
      suggest that in swine models, the optimal treatment for venlafaxine overdose
      would include vasopressin with lipids.

PMID- 27046187
TI  - Pilonidal Sinus Disease: A 10-Year Review Reveals Occupational Risk Factors and
      the Superiority of the Minimal Surgery Trephine Technique.
AB  - OBJECTIVES: To identify military occupational risk factors for pilonidal sinus
      disease (PSD) and to compare an Army Clinic minimal surgery with techniques used
      at public hospitals. METHODS: Review of a historical cohort of soldiers (3,407
      with PSD) to determine PSD risk factors in military personnel and comparison of
      postoperative sick leave days between surgical techniques. RESULTS: Male and
      female officers had a lower PSD incidence, whereas male combatants and female
      drivers were at higher risk compared to administrative personnel. The minimal
      surgery technique used at the Army Clinic was associated with an average 13 less
      postoperative sick leave days per patient, as compared to the surgical techniques
      including wide excision used at public hospitals. Compared to healthy soldiers,
      the relative risk for PSD recurrence was 7.87 in all males and 9.54 in male
      combatants. CONCLUSIONS: Male combatants and female drivers are at higher risk
      for PSD, whereas officers and administrative personnel are at lower risk.
      Compared with surgical techniques used at public hospitals, the Army Clinic
      exclusive use of the Gips minimal surgery technique is associated with fewer sick
      leave days. Prior surgery for PSD is a positive predictor of recurrence, and
      these patients warrant secondary prevention.

PMID- 27046188
TI  - The Detmold Knife and the Empty Sleeve.

PMID- 27046190
TI  - Impact of Binding Site Comparisons on Medicinal Chemistry and Rational Molecular
      Design.
AB  - Modern rational drug design not only deals with the search for ligands binding to
      interesting and promising validated targets but also aims to identify the
      function and ligands of yet uncharacterized proteins having impact on different
      diseases. Additionally, it contributes to the design of inhibitors with distinct
      selectivity patterns and the prediction of possible off-target effects. The
      identification of similarities between binding sites of various proteins is a
      useful approach to cope with those challenges. The main scope of this perspective
      is to describe applications of different protein binding site comparison
      approaches to outline their applicability and impact on molecular design. The
      article deals with various substantial application domains and provides some
      outstanding examples to show how various binding site comparison methods can be
      applied to promote in silico drug design workflows. In addition, we will also
      briefly introduce the fundamental principles of different protein binding site
      comparison methods.

PMID- 27046189
TI  - The Role of Heat Shock Protein 90B1 in Patients with Polycystic Ovary Syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a heterogenetic disorder in women that is
      characterized by arrested follicular growth and anovulatory infertility. The
      altered protein expression levels in the ovarian tissues reflect the molecular
      defects in folliculogenesis. To identify aberrant protein expression in PCOS, we
      analyzed protein expression profiles in the ovarian tissues of patients with
      PCOS. We identified a total of 18 protein spots that were differentially
      expressed in PCOS compared with healthy ovarian samples. A total of 13 proteins
      were upregulated and 5 proteins were downregulated. The expression levels of heat
      shock protein 90B1 (HSP90B1) and calcium signaling activator calmodulin 1 (CALM1)
      were increased by at least two-fold. The expression levels of HSP90B1 and CALM1
      were positively associated with ovarian cell survival and negatively associated
      with caspase-3 activation and apoptosis. Knock-down of HSP90B1 with siRNA
      attenuated ovarian cell survival and increased apoptosis. In contrast, ovarian
      cell survival was improved and cell apoptosis was decreased in cells over
      expressing HSP90B1. These results demonstrated the pivotal role of HSP90B1 in the
      proliferation and survival of ovarian cells, suggesting a critical role for
      HSP90B1 in the pathogenesis of PCOS. We also observed a downregulation of anti
      inflammatory activity-related annexin A6 (ANXA6) and tropomyosin 2 (TPM2)
      compared with the normal controls, which could affect cell division and
      folliculogenesis in PCOS. This is the first study to identify novel altered gene
      expression in the ovarian tissues of patients with PCOS. These findings may have
      significant implications for future diagnostic and treatment strategies for PCOS
      using molecular interventions. 

PMID- 27046191
TI  - Immunotoxicity of beta-Diketone Antibiotic Mixtures to Zebrafish (Danio rerio) by
      Transcriptome Analysis.
AB  - Fluoroquinolones and tetracyclines are known as beta-diketone antibiotics (DKAs)
      because of bearing a diketone group in their molecular structure. DKAs are the
      most widely used antibiotics to prevent generation of disease in humans and
      animals and to suppress bacterial growth in aquaculture. In recent years, overuse
      of DKAs has caused serious environmental risk due to their pseudo-persistence in
      the environment, even though their half-lives are not long. So far, no reports
      were concerned with the joint immunotoxicity of DKAs. Herein, we reported on the
      immunotoxicity of DKAs on zebrafish after a 3-month DKAs exposure using
      transcriptomic techniques. According to transcriptome sequencing, 10
      differentially expressed genes were screened out among the genes related to KEGG
      pathways with high enrichment. The identified 7 genes showed to be consistent
      between RNA-seq and qRT-PCR. Due to DKAs exposure, the content or activity for a
      series of immune-related biomarkers (Complement 3, lysozyme, IgM and AKP) showed
      the inconsistent changing trends as compared with the control group.
      Histopathological observations showed that the number of goblet cells increased
      sharply, the columnar epithelial cells swelled, the nucleus became slender in
      intestinal villi, and numerous brown metachromatic granules occurred in spleens
      of DKAs-exposed groups. Overall, both detection of biomarkers and
      histopathological observation corroborated that chronic DKAs exposure could
      result in abnormal expression of immune genes and enzymes, and variable levels of
      damage to immune-related organs. These complex effects of DKAs may lead to
      zebrafish dysfunction and occurrence of diseases related to the immune system. 

PMID- 27046193
TI  - Correction: Leader-Containing Uncapped Viral Transcript Activates RIG-I in
      Antiviral Stress Granules.

PMID- 27046192
TI  - Comparative functional properties of engineered cationic antimicrobial peptides
      consisting exclusively of tryptophan and either lysine or arginine.
AB  - We previously reported a series of de novo engineered cationic antibiotic
      peptides (eCAPs) consisting exclusively of arginine and tryptophan (WR) that
      display potent activity against diverse multidrug-resistant (MDR) bacterial
      strains. In this study, we sought to examine the influence of arginine compared
      to lysine on antibacterial properties by direct comparison of the WR peptides (8
      18 residues) with a parallel series of engineered peptides containing only lysine
      and tryptophan. WR and WK series were compared for antibacterial activity by
      bacterial killing and growth inhibition assays and for mechanism of peptide
      bacteria interactions by surface plasmon resonance and flow cytometry. Mammalian
      cytotoxicity was also assessed by flow cytometry, haemolytic and tetrazolium
      based assays. The shortest arginine-containing peptides (8 and 10 mers) displayed
      a statistically significant increase in activity compared to the analogous lysine
      containing peptides. The WR and WK peptides achieved maximum antibacterial
      activity at the 12-mer peptide (WK12 or WR12). Further examination of
      antibacterial mechanisms of the optimally active 12-mer peptides using surface
      plasmon resonance and flow cytometry demonstrates stronger interactions with
      Pseudomonasaeruginosa, greater membrane permeabilizing activity, and lower
      inhibitory effects of divalent cations on activity and membrane permeabilization
      properties of WR12 compared to WK12 (P < 0.05). Importantly, WK12 and WR12
      displayed similar negligible haemolytic and cytotoxic effects at peptide
      concentrations up to ten times the MIC or 20 times the minimum bactericidal
      concentration. Thus, arginine, compared to lysine, can indeed yield enhanced
      antibacterial activity to minimize the required length to achieve functional
      antimicrobial peptides. 

PMID- 27046197
TI  - Characterization of the MMP/TIMP Imbalance and Collagen Production Induced by IL
      1beta or TNF-alpha Release from Human Hepatic Stellate Cells.
AB  - Inflammation has an important role in the development of liver fibrosis in
      general and the activation of hepatic stellate cells (HSCs) in particular. It is
      known that HSCs are themselves able to produce cytokines and chemokines, and that
      this production may be a key event in the initiation of fibrogenesis. However,
      the direct involvement of cytokines and chemokines in HSC (self-)activation
      remains uncertain. In this study, the effects of pro-inflammatory cytokines IL
      1alpha and beta, TNF-alpha, and IL-8 on the activation state of HSCs were
      examined, in comparison to the pro-fibrogenic mediator TGF-beta1. LX-2 cells were
      stimulated for 24 or 48 hours with recombinant human form of the pro-inflammatory
      cytokines IL-1alpha and beta, TNF-alpha, and IL-8, and also the pro-fibrogenic
      mediator TGF-beta1. Two drugs were also evaluated, the anti-TNF-alpha monoclonal
      antibody infliximab and the IL-1 receptor antagonist anakinra, regarding their
      inhibitory effects. In LX-2 human HSC, treatment with TGF-beta1 are associated
      with downregulation of the metalloproteinase (MMP)-1 and MMP-3, with upregulation
      of tissue inhibitor of metalloproteinase (TIMP)-1, collagen type I alpha1,
      collagen type IV alpha1, alpha-SMA, endothelin-1 and PDGF-BB. Cytokines and
      chemokines expression were found to be downregulated, excepting IL-6. In
      contrast, we observed that LX-2 exposure to IL-1, TNF-alpha and IL-8 can reverse
      the phenotype of pro-fibrogenic activated cells. Indeed, MMP-1, MMP-3 and MMP-9
      were found elevated, associated with downregulation of alpha-SMA and/or PDGF-BB,
      and a greater expression of IL-1beta, IL-6, IL-8, CXCL1 and CCL2. Lastly, we
      found that infliximab and anakinra successfully inhibits effects of TNF-alpha and
      IL-1 respectively in LX-2 cells. Infliximab and anakinra may be of value in
      preclinical trials in chronic liver disease. Overall, our results suggest that
      (i) pro-inflammatory mediators exert complex effects in HSCs via an MMP/TIMP
      imbalance, and (ii) targeting IL-1 signaling may be a potentially valuable
      therapeutic strategy in chronic liver diseases. 

PMID- 27046198
TI  - Correction to: Hum Gene Ther 2016;27(1):19-31.

PMID- 27046199
TI  - R-Spondins Are Expressed by the Intestinal Stroma and are Differentially
      Regulated during Citrobacter rodentium- and DSS-Induced Colitis in Mice.
AB  - The R-spondin family of proteins has recently been described as secreted
      enhancers of beta-catenin activation through the canonical Wnt signaling pathway.
      We previously reported that Rspo2 is a major determinant of susceptibility to
      Citrobacter rodentium-mediated colitis in mice and recent genome-wide association
      studies have revealed RSPO3 as a candidate Crohn's disease-specific inflammatory
      bowel disease susceptibility gene in humans. However, there is little information
      on the endogenous expression and cellular source of R-spondins in the colon at
      steady state and during intestinal inflammation. RNA sequencing and qRT-PCR were
      used to assess the expression of R-spondins at steady state and in two mouse
      models of colonic inflammation. The cellular source of R-spondins was assessed in
      specific colonic cell populations isolated by cell sorting. Data mining from
      publicly available datasets was used to assess the expression of R-spondins in
      the human colon. At steady state, colonic expression of R-spondins was found to
      be exclusive to non-epithelial CD45- lamina propria cells, and Rspo3/RSPO3 was
      the most highly expressed R-spondin in both mouse and human colon. R-spondin
      expression was found to be highly dynamic and differentially regulated during C.
      rodentium infection and dextran sodium sulfate (DSS) colitis, with notably high
      levels of Rspo3 expression during DSS colitis, and high levels of Rspo2
      expression during C. rodentium infection, specifically in susceptible mice. Our
      data are consistent with the hypothesis that in the colon, R-spondins are
      expressed by subepithelial stromal cells, and that Rspo3/RSPO3 is the family
      member most implicated in colonic homeostasis. The differential regulation of the
      R-spondins in different models of intestinal inflammation indicate they respond
      to specific pathogenic and inflammatory signals that differ in the two models and
      provides further evidence that this family of proteins plays a key role in
      linking intestinal inflammation and homeostasis. 

PMID- 27046201
TI  - Water-in-Oil Microstructures Formed by Marine Oil Dispersants in a Model Crude
      Oil.
AB  - DOSS (dioctyl sodium sulfosuccinate), Tween 80, and Span 80, surfactants commonly
      used in marine crude oil spill dispersants, have been mixed into a model oil at a
      total surfactant concentration of 2 wt %, typical for dispersant-treated oil
      slicks. These surfactant-oil blends also contained 0.5-1.5 wt % synthetic
      seawater to enable formation of water-in-oil (W/O) microstructures. Trends in
      dynamic oil-seawater interfacial tension (IFT) as a function of surfactant blend
      composition are similar to those observed in prior work for crude oil treated
      with similar blends of these surfactants. In particular, Span 80-rich surfactant
      blends exhibit much slower initial dynamic IFT decline than DOSS-rich surfactant
      blends in both model oil and crude oil, and surfactant blends containing 50 wt %
      Tween 80 and a DOSS:Span 80 ratio near 1:1 produce ultralow IFT in the model oil
      (<10(-4) mN/m) just as similar surfactant blends do in crude oil. At all
      DOSS:Span 80 ratios, surfactant blends containing 50 wt % Tween 80 form clear
      solutions with seawater in the model oil. Cryo-transmission electron microscopy
      (cryo-TEM) and dynamic light scattering (DLS) show that these solutions contain
      spherical W/O microstructures, the size and dispersity of which vary with
      surfactant blend composition and surfactant:seawater molar ratio. Span 80-rich
      microstructures exhibit high polydispersity index (PDI > 0.2) and large diameters
      (>=100 nm), whereas DOSS-rich microstructures exhibit smaller diameters (20-40
      nm) and low polydispersity index (PDI < 0.1), indicating a narrow microstructure
      size distribution. The smaller diameters of DOSS-rich microstructures, as well as
      the fact that DOSS molecules, being oil-soluble, can diffuse to a bulk oil-water
      interface as monomers much faster than any of these microstructures, may explain
      why DOSS-rich blends adsorb to the oil-water interface more quickly than Span 80
      rich blends, a phenomenon which has been linked in prior work to the higher
      effectiveness of DOSS-rich Tween/Span/DOSS-based oil dispersants.

PMID- 27046200
TI  - Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 Point-of
      Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in
      Durban, South Africa.
AB  - In South Africa, various point-of-care hemoglobin meters are used. However, the
      regulatory framework for approval, implementation and oversight of use of point
      of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of
      the HemoCue Hb 301, STAT-Site MHgb and URIT-12 point-of-care hemoglobin meters,
      compared to a central laboratory based reference assay, in a central laboratory
      and a community based clinic in Durban, South Africa. Differences in performance
      of the point-of-care assays, compared to the reference assay, were more
      pronounced in the community based clinic. Results were reasonable for the HemoCue
      Hb 301, but poor for the STAT-Site MHgb and the URIT-12. Poor test performance of
      point-of-care hemoglobin meters, and inadequate evaluations and oversight in
      South Africa, leads to suboptimal clinical care and clinical research, and
      increased costs. There is a need for proper evaluation and quality assurance of
      point-of-care tests, the results of which should be made widely available to key
      stakeholders. 

PMID- 27046202
TI  - Utility of direct susceptibility testing on blood cultures: is it still
      worthwhile?
AB  - Earlier targeted therapy for bacteraemia optimizes patient outcomes and reduces
      broad spectrum antibiotic use. Standardized susceptibility testing results are
      available at 36-48 h. Direct disc susceptibility testing from blood culture broth
      reduces time to results but the inoculum is not standardized. No studies have
      looked at the clinical utility of direct susceptibility results. This
      retrospective cohort study aimed to assess the correlation between direct and
      formal testing methods as well as the clinical utility of direct susceptibility
      results. 160 episodes of bacteraemia with paired direct and formal susceptibility
      testing were studied. Direct disc testing was performed on blood culture broth.
      Formal testing was performed on isolates, using automated broth microdilution or
      Etests. The rate of error was 9.0 % (95 % CI 7.0-11.6 %). In 10 cases (6.3 %, 95
      % CI 3.0-11.2 %), inappropriate antibiotics were used due to direct
      susceptibility results, including two cases with ineffective (as opposed to too
      broad) antibiotics being used. Antibiotics were changed in 28.1 % of cases once
      direct susceptibility data was available. There was a decreased time to effective
      antibiotics in 9.3 % (95 % CI 5.3-15.0 %), and a decreased time to a targeted
      antibiotics in 14.3 % (95 % CI 9.3-20.8 %) of cases. Despite the error rate, the
      advantages of earlier times to effective and targeted antibiotics justifies
      continuing direct testing in bacteraemia episodes with Gram-negative rods. In the
      Gram-positive group, given the contamination rate, the availability of adjunctive
      PCR, and the fact that early identification of the isolate could equally
      influence antibiotic choices, direct susceptibility testing may no longer be
      warranted. 

PMID- 27046204
TI  - Stoichiometric determination of moisture in edible oils by Mid-FTIR spectroscopy.
AB  - A simple and accurate method for the determination of moisture in edible oils by
      differential FTIR spectroscopy has been devised based on the stoichiometric
      reaction of the moisture in oil with toluenesulfonyl isocyanate (TSI) to produce
      CO2. Calibration standards were devised by gravimetrically spiking dry dioxane
      with water, followed by the addition of neat TSI and examination of the
      differential spectra relative to the dry dioxane. In the method, CO2 peak area
      changes are measured at 2335 cm(-1) and were shown to be related to the amount of
      moisture added, with any CO2 inherent to residual moisture in the dry dioxane
      subtracted ratioed out. CO2 volatility issues were determined to be minimal, with
      the overall SD of dioxane calibrations being ~18 ppm over a range of 0-1000 ppm.
      Gravimetrically blended dry and water-saturated oils analysed in a similar manner
      produced linear CO2 responses with SD's of <15 ppm on average. One set of dry-wet
      blends was analysed in duplicate by FTIR and by two independent laboratories
      using coulometric Karl Fischer (KF) procedures. All 3 methods produced highly
      linear moisture relationships with SD's of 7, 16 and 28 ppm, respectively over a
      range of 200-1500 ppm. Although the absolute moisture values obtained by each
      method did not exactly coincide, each tracked the expected moisture changes
      proportionately. The FTIRTSI-H2O method provides a simple and accurate
      instrumental means of determining moisture in oils rivaling the accuracy and
      specificity of standard KF procedures and has the potential to be automated. It
      could also be applied to other hydrophobic matrices and possibly evolve into a
      more generalized method, if combined with polar aprotic solvent extraction.

PMID- 27046203
TI  - Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary
      Disease.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with
      subclinical systemic atherosclerosis and pulmonary vascular remodelling
      characterized by intimal hyperplasia and luminal narrowing. We aimed to determine
      differences in the intimal thickening of systemic and pulmonary arteries in COPD
      subjects and smokers. Secondary aims include comparisons with a non-smokers
      group; determining the clinical variables associated with systemic and pulmonary
      intimal thickening, and the correlations between systemic and pulmonary
      remodelling changes. METHODS: All consecutive subjects undergoing lung resection
      were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers.
      Sections of the 5th intercostal artery and muscular pulmonary arteries were
      measured by histo-morphometry. Four parameters of intimal thickening were
      evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal
      narrowing, 3) intimal thickness index, and 4) intima-to-media ratio. RESULTS: In
      the adjusted analysis, the systemic arteries of COPD subjects showed greater
      intimal thickening (%IA) than those of smokers (15.6+/-1.5% vs. 14.2+/-1.6%, p =
      0.038). In the pulmonary arteries, significant differences were observed for %IA
      between the 2 groups (37.3+/-2.2% vs. 29.3+/-2.3%, p = 0.016). Among clinical
      factors, metabolic syndrome, gender and COPD status were associated with the
      systemic intimal thickening, while only COPD status was associated with pulmonary
      intimal thickening. A correlation between the %IA of the systemic and pulmonary
      arteries was observed (Spearman's rho = 0.46, p = 0.008). CONCLUSIONS: Greater
      intimal thickening in systemic and pulmonary arteries is observed in COPD
      patients than in smokers. There is a correlation between systemic and pulmonary
      vascular remodelling in the overall population.

PMID- 27046205
TI  - Determination of phosphorus in natural waters: A historical review.
AB  - The aim of this paper is to introduce a virtual special issue that reviews the
      development of analytical approaches to the determination of phosphorus species
      in natural waters. The focus is on sampling and sample treatment, analytical
      methods and quality assurance of the data. The export of phosphorus from
      anthropogenic activities (from diffuse and point sources) can result in increased
      primary production and eutrophication, and potentially the seasonal development
      of toxic algal blooms, which can significantly impact on water quality. Therefore
      the quantification of phosphorus species in natural waters provides important
      baseline data for studying aquatic phosphorus biogeochemistry, assessing
      ecosystem health and monitoring compliance with legislation. 

PMID- 27046206
TI  - Development of a Total Organic Carbon method for the quantitative determination
      of solubility enhancement by cyclodextrins: Application to essential oils.
AB  - Formation of inclusion complexes with cyclodextrins (CDs) is known to enhance
      guest solubility in aqueous medium. Different techniques allow determining the
      evolution in solubility of individual guest compounds. However, examination of
      mixtures solubility encapsulated in CDs is still a challenge. This is mainly
      related to the difference in the response of mixture components to the applied
      technique or to the fact that most of the conventional methods examine the signal
      of an individual constituent of the mixture. Thus, applying current techniques
      may not reflect the behavior of the whole mixture. Here, we used for the first
      time Total Organic Carbon (TOC) analysis to explore and assess the efficiency of
      2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to enhance the solubility of
      natural complex mixtures such as essential oils (EOs). Phase solubility studies
      were performed for eleven EOs with HP-beta-CD. The TOC method has provided good
      validation parameters for linearity, precision and accuracy. For further
      validation of the method, phase solubility studies were performed with HP-beta-CD
      for eugenol, as a model EO component. The eugenol solubility was determined by UV
      Visible and TOC analyses in order to compare the results. Data obtained from both
      methods were similar (p < 0.05), thereby proving the effectiveness of the
      developed TOC method. Finally, the phase solubility diagrams of EOs showed that
      the solubilizing potential of CD increased proportionally with the decrease in EO
      intrinsic solubility. Results proved that TOC could be successfully applied to
      investigate CD/guest inclusion complexes and is expected to have a broad range of
      applications in the field of mixtures encapsulation. 

PMID- 27046207
TI  - Electrochemical sensors for the simultaneous determination of zinc, cadmium and
      lead using a Nafion/ionic liquid/graphene composite modified screen-printed
      carbon electrode.
AB  - A simple, low cost, and highly sensitive electrochemical sensor, based on a
      Nafion/ionic liquid/graphene composite modified screen-printed carbon electrode
      (N/IL/G/SPCE) was developed to determine zinc (Zn(II)), cadmium (Cd(II)), and
      lead (Pb(II)) simultaneously. This disposable electrode shows excellent
      conductivity and fast electron transfer kinetics. By in situ plating with a
      bismuth film (BiF), the developed electrode exhibited well-defined and separate
      peaks for Zn(II), Cd(II), and Pb(II) by square wave anodic stripping voltammetry
      (SWASV). Analytical characteristics of the BiF/N/IL/G/SPCE were explored with
      calibration curves which were found to be linear for Zn(II), Cd(II), and Pb(II)
      concentrations over the range from 0.1 to 100.0 ng L(-1). With an accumulation
      period of 120 s detection limits of 0.09 ng mL(-1), 0.06 ng L(-1) and 0.08 ng L(
      1) were obtained for Zn(II), Cd(II) and Pb(II), respectively using the
      BiF/N/IL/G/SPCE sensor, calculated as 3sigma value of the blank. In addition, the
      developed electrode displayed a good repeatability and reproducibility. The
      interference from other common ions associated with Zn(II), Cd(II) and Pb(II)
      detection could be effectively avoided. Finally, the proposed analytical
      procedure was applied to detect the trace metal ions in drinking water samples
      with satisfactory results which demonstrates the suitability of the
      BiF/N/IL/G/SPCE to detect heavy metals in water samples and the results agreed
      well with those obtained by inductively coupled plasma mass spectrometry.

PMID- 27046208
TI  - A highly thermal stable solid phase microextraction fiber prepared by an
      inorganic binder.
AB  - An easy method to prepare solid phase microextraction fibers by introducing an
      inorganic binder was demonstrated in this study, where MoS2 was selected as the
      extraction phase material because of its graphite-like layered structure with
      large specific adsorption area and good stability, and was then adhered to a
      stainless steel wire by acid aluminum phosphate binder with the spraying method.
      The as-prepared solid phase microextraction fiber coupled with gas chromatography
      was then used to extract some polycyclic aromatic hydrocarbons target analytes
      including the low-volatile benzo(a)pyrene etc. from a standard sample. Comparing
      with the MoS2-epoxy resin and commercial polyacrylate fibers, the MoS2-acid
      aluminum phosphate fiber has a higher thermal stability because of highly thermal
      stable acid aluminum phosphate, which is durable for a long service life at a
      high temperature (320  degrees C), and has the advantage in the extraction of low
      volatility analytes. After the optimization of adsorption and desorption factors
      (ionic strength, adsorption time and temperature, and desorption temperature),
      method detection limits of <0.1 MUg L(-1) were achieved, and the calibration
      curves were all linear (R(2) >= 0.9981) within the range of 0.1-100 MUg L(-1).
      The satisfying repeatability was also achieved, the RSD values of single-fiber
      were 3.49-5.81%, and the ones of fiber-to-fiber were 5.32-7.22%. As a result, the
      present fiber with good thermal stability can work at high temperature for a long
      service life, which is useful for the detection of low-volatility target analytes
      in practical applications.

PMID- 27046209
TI  - Application of solid phase microextraction and needle trap device with silica
      composite of carbon nanotubes for determination of perchloroethylene in
      laboratory and field.
AB  - In this paper solid phase microextraction (SPME) and needle trap device (NTD) as
      two in-progress air monitoring techniques was applied with silylated composite of
      carbon nanotubes for sampling and analysis of perchloroethylene in air.
      Application of SPME and NTD with proposed nano-structured sorbent was
      investigated under different laboratory and experimental parameters and compared
      to the SPME and NTD with CAR/PDMS. Finally the two samplers contained nano
      sorbent used as a field sampler for sampling and analysis of perchloroethylene in
      dry cleaning. Results revealed that silica composite form of CNTs showed better
      performance for adsorbent of perchloroethylene. SPME and NTD with proposed
      sorbent was demonstrated better responses in lower levels of temperature and
      relative humidity. For 5 days from sampling the relative responses were more than
      97% and 94% for NTD and SPME, respectively. LOD were 0.023 and 0.014 ng mL(-1)
      for SPME coated CNTs/SC and CAR/PDMS, and 0.014 and 0.011 ng mL(-1) for NTD
      packed with CNTs/SC and CAR/PDMS, respectively. And for consecutive analysis RSD
      were 3.9-6.7% in laboratory and 4.43-6.4% in the field. In the field study, NTD
      was successfully applied for determining of the PCE in dry cleaning. The results
      show that the NTD packed with nanomaterial is a reliable and effective approach
      for the sampling and analysis of volatile compounds in air. 

PMID- 27046210
TI  - Structural characterization of antibody drug conjugate by a combination of
      intact, middle-up and bottom-up techniques using sheathless capillary
      electrophoresis - Tandem mass spectrometry as nanoESI infusion platform and
      separation method.
AB  - Antibody-drug conjugates (ADCs) represent a fast growing class of biotherapeutic
      products. Their production leads to a distribution of species exhibiting
      different number of conjugated drugs overlaying the inherent complexity resulting
      from the monoclonal antibody format, such as glycoforms. ADCs require an
      additional level of characterization compared to first generation of
      biotherapeutics obtained through multiple analytical techniques for complete
      structure assessment. We report the development of complementary approaches
      implementing sheathless capillary electrophoresis-mass spectrometry (sheathless
      CE-MS) to characterize the different aspects defining the structure of
      brentuximab vedotin. Native MS using sheathless CE-MS instrument as a nanoESI
      infusion platform enabled accurate mass measurements and estimation of the
      average drug to antibody ratio alongside to drug load distribution. Middle-up
      analysis performed after limited IdeS proteolysis allowed to study independently
      the light chain, Fab and F(ab')2 subunits incorporating 1, 0 to 4 and 0 to 8
      payloads respectively. Finally, a CZE-ESI-MS/MS methodology was developed in
      order to be compatible with hydrophobic drug composing ADCs. From a single
      injection, complete sequence coverage could be achieved. Using the same dataset,
      glycosylation and drug-loaded peptides could be simultaneously identified
      revealing robust information regarding their respective localization and
      abundance. Drug-loaded peptide fragmentation mass spectra study demonstrated drug
      specific fragments reinforcing identification confidence, undescribed so far.
      Results reveal the method ability to characterize ADCs primary structure in a
      comprehensive manner while reducing tremendously the number of experiments
      required. Data generated showed that sheathless CZE-ESI-MS/MS characteristics
      position the methodology developed as a relevant alternative for comprehensive
      multilevel characterization of these complex biomolecules. 

PMID- 27046211
TI  - Integrated, paper-based potentiometric electronic tongue for the analysis of beer
      and wine.
AB  - The following manuscript details the stages of construction of a novel paper
      based electronic tongue with an integrated Ag/AgCl reference, which can operate
      using a minimal amount of sample (40 MUL). First, we optimized the fabrication
      procedure of silver electrodes, testing a set of different methodologies
      (electroless plating, use of silver nanoparticles and commercial silver paints).
      Later a novel, integrated electronic tongue system was assembled with the use of
      readily available materials such as paper, wax, lamination sheets, bleach etc.
      New system was thoroughly characterized and the ion-selective potentiometric
      sensors presented performance close to theoretical. An electronic tongue,
      composed of electrodes sensitive to sodium, calcium, ammonia and a cross
      sensitive, anion-selective electrode was used to analyze 34 beer samples (12
      types, 19 brands). This system was able to discriminate beers from different
      brands, and types, indicate presence of stabilizers and antioxidants, dyes or
      even unmalted cereals and carbohydrates added to the fermentation wort. Samples
      could be classified by type of fermentation (low, high) and system was able to
      predict pH and in part also alcohol content of tested beers. In the next step
      sample volume was minimalized by the use of paper sample pads and measurement in
      flow conditions. In order to test the impact of this advancement a four electrode
      system, with cross-sensitive (anion-selective, cation-selective, Ca(2+)/Mg(2+),
      K(+)/Na(+)) electrodes was applied for the analysis of 11 types of wine (4 types
      of grapes, red/white, 3 countries). Proposed matrix was able to group wines
      produced from different varieties of grapes (Chardonnay, Americanas, Malbec,
      Merlot) using only 40 MUL of sample. Apart from that, storage stability studies
      were performed using a multimeter, therefore showing that not only fabrication
      but also detection can be accomplished by means of off-the-shelf components. This
      manuscript not only describes new paper-based, potentiometric sensors but also
      according to our knowledge is the first description of an electrochemical paper
      based electronic tongue with integrated reference.

PMID- 27046212
TI  - Multiplex sorting of foodborne pathogens by on-chip free-flow magnetophoresis.
AB  - This study reports multiplex sorting of Salmonella typhimurium and Escherichia
      coli 0157, from broth cultures and from pathogen-spiked skinned chicken breast
      enrichment broths by employing microfluidic free-flow magnetophoresis. Magnetic
      beads of different sizes and magnetite content, namely Dynabeads anti-salmonella
      and Hyglos-Streptavidin beads together with the corresponding pathogen-specific
      biotinylated recombinant phages, were utilised as affinity solid phases for the
      capture and concentration of viable S. typhimurium and E. coli 0157. Following
      optimisation, the protocol was used to demonstrate continuous magnetophoretic
      sorting of the two pathogen-bound magnetic bead populations from mixed cultures
      and from pathogen-spiked chicken pre-enrichment broths under the influence of a
      Halbach magnet array. For example, in the latter case, a pure population of S.
      typhimurium-bound Dynabeads (72% recovery) was sorted from a 100 MUL mixture
      containing E. coli 0157-bound Hyglos beads (67% recovery) within 1.2 min in the
      presence of 0.1% Tween 20. This proof-of-principle study demonstrates how more
      than one pathogen type can be simultaneously isolated/enriched from a single food
      pre-enrichment broth (e.g. Universal food enrichment broth). 

PMID- 27046213
TI  - Nanocomposite of bimetallic nanodendrite and reduced graphene oxide as a novel
      platform for molecular imprinting technology.
AB  - In this present work, for the first time, we are reporting a green synthesis
      approach for the preparation of vinyl modified reduced graphene oxide-based
      magnetic and bimetallic (Fe/Ag) nanodendrite (RGO@BMNDs). Herein, the RGO@BMNDs
      acts as a platform for the synthesis of the pyrazinamide (PZA)-imprinted polymer
      matrix and used for designing of the electrochemical sensor. We have demonstrated
      how the change in morphology could affect the electrochemical and magnetic
      property of nanomaterials and for this the reduced graphene oxide-based
      bimetallic nanoparticle (Fe/Ag) was also prepared It was found that the
      combination of graphene and bimetallic nanodendrites shows improvement as well as
      enhancement in the electrocatalytic activity and adsorption capacity, in
      comparison to their respective nanoparticles. The application of imprinted
      RGO@BMNDs sensor was explored for trace level detection of PZA (Limit of
      detection = 6.65 pg L(-1), S/N = 3), which is a drug used for the cure of
      Tuberculosis. This is lowest detection limit reported so far for the detection of
      PZA. The sensor is highly selective, cost-effective, simple and free from any
      interfering effect. The real time application of the sensor was explored by
      successful detection of PZA in pharmaceutical and human blood serum, plasma and
      urine samples. 

PMID- 27046214
TI  - An ultrasensitive lysozyme chemiluminescence biosensor based on surface molecular
      imprinting using ionic liquid modified magnetic graphene oxide/beta-cyclodextrin
      as supporting material.
AB  - In this work, ionic liquid modified Fe3O4@dopamine/graphene oxide/beta
      cyclodextrin (ILs-Fe3O4@DA/GO/beta-CD) was used as supporting material to
      synthesize surface molecularly imprinted polymer (SMIP) which then was introduced
      into chemiluminescence (CL) to achieve an ultrasensitive and selective biosensor
      for determination of lysozyme (Lys). ILs and beta-CD was applied to provide
      multiple binding sites to prepare Lys SMIP and Fe3O4@DA was designed to make the
      product separate easily and prevent the aggregation of GO which could improve
      absorption capacity for its large specific surface area. The ILs-Fe3O4@DA/GO/beta
      CD-SMIP showed high adsorption capacity (Q = 101 mg/g) to Lys in the adsorption
      isotherm assays. The adsorption equilibrium was reached within 10 min for all the
      concentrations, attributing to the binding sites situated exclusively at the
      surface, and the adsorption model followed Langmuir isotherm. Under the suitable
      CL conditions, the proposed biosensor could response Lys linearly in the range of
      1.0 * 10(-9)-8.0 * 10(-8) mg/mL with a detection limit of 3.0 * 10(-10) mg/mL.
      When used in practical samples in determination of Lys, the efficient biosensor
      exhibited excellent result with the recoveries ranging from 94% to 112%. 

PMID- 27046215
TI  - Fabrication of an electrochemical sensor based on spiropyran for sensitive and
      selective detection of fluoride ion.
AB  - In the past decades, numerous electrochemical sensors based on exogenous
      electroactive substance have been reported. Due to non-specific interaction
      between the redox mediator and the target, the instability caused by false signal
      may not be avoided. To address this issue, in this paper, a new electrochemical
      sensor based on spiropyran skeleton, namely SPOSi, was designed for specific
      electrochemical response to fluoride ions (F(-)). The breakage of Si-O induced by
      F(-) based on the specific nucleophilic substitution reaction between F(-) and
      silica would directly produce a hydroquinone structure for electrochemical signal
      generation. To improve the sensitivity, SPOSi probe was assembled on the single
      walled carbon nanotubes (SWCNTs) modified glassy carbon electrode (GCE) through
      the pi-pi conjugating interaction. This electrode was successfully applied to
      monitor F(-) with a detection limit of 8.3 * 10(-8) M. Compared with the
      conventional F(-) ion selected electrode (ISE) which utilized noncovalent
      interaction, this method displays higher stability and a comparable sensitivity
      in the urine samples. 

PMID- 27046216
TI  - Balancing surface adsorption and diffusion of lithium-polysulfides on
      nonconductive oxides for lithium-sulfur battery design.
AB  - Lithium-sulfur batteries have attracted attention due to their six-fold specific
      energy compared with conventional lithium-ion batteries. Dissolution of lithium
      polysulfides, volume expansion of sulfur and uncontrollable deposition of lithium
      sulfide are three of the main challenges for this technology. State-of-the-art
      sulfur cathodes based on metal-oxide nanostructures can suppress the shuttle
      effect and enable controlled lithium sulfide deposition. However, a clear
      mechanistic understanding and corresponding selection criteria for the oxides are
      still lacking. Herein, various nonconductive metal-oxide nanoparticle-decorated
      carbon flakes are synthesized via a facile biotemplating method. The cathodes
      based on magnesium oxide, cerium oxide and lanthanum oxide show enhanced cycling
      performance. Adsorption experiments and theoretical calculations reveal that
      polysulfide capture by the oxides is via monolayered chemisorption. Moreover, we
      show that better surface diffusion leads to higher deposition efficiency of
      sulfide species on electrodes. Hence, oxide selection is proposed to balance
      optimization between sulfide-adsorption and diffusion on the oxides. 

PMID- 27046217
TI  - Artificial water channels--incipient innovative developments.
AB  - Aquaporins (AQPs) are biological water channels known for fast water transport
      (~10(8)-10(9) water molecules per s per channel), with complete proton/ion
      exclusion. Few synthetic channels have been designed to mimic this high water
      permeability and to reject ions at a significant level. This Feature Article will
      discuss the incipient developments of the first artificial water channel systems.

PMID- 27046218
TI  - Artifact reduction in short-scan CBCT by use of optimization-based
      reconstruction.
AB  - Increasing interest in optimization-based reconstruction in research on, and
      applications of, cone-beam computed tomography (CBCT) exists because it has been
      shown to have to potential to reduce artifacts observed in reconstructions
      obtained with the Feldkamp-Davis-Kress (FDK) algorithm (or its variants), which
      is used extensively for image reconstruction in current CBCT applications. In
      this work, we carried out a study on optimization-based reconstruction for
      possible reduction of artifacts in FDK reconstruction specifically from short
      scan CBCT data. The investigation includes a set of optimization programs such as
      the image-total-variation (TV)-constrained data-divergency minimization, data
      weighting matrices such as the Parker weighting matrix, and objects of practical
      interest for demonstrating and assessing the degree of artifact reduction.
      Results of investigative work reveal that appropriately designed optimization
      based reconstruction, including the image-TV-constrained reconstruction, can
      reduce significant artifacts observed in FDK reconstruction in CBCT with a short
      scan configuration. 

PMID- 27046219
TI  - Delirium associated with concomitant use of duloxetine and bupropion in an
      elderly patient.
AB  - Delirium is common in daily practice. Drug-induced delirium constitutes
      approximately one-third of all cases of delirium. In cases characterized by the
      limited efficacy of a single antidepressant, a combination of two antidepressants
      is required, which may induce a complex drug-drug interaction. We reviewed a case
      of duloxetine- and bupropion-related delirium in an elderly male patient in our
      clinical practice. The patient was diagnosed with major depressive disorder and
      was treated with duloxetine. However, he developed delirium 10 days after
      bupropion was added to his treatment regimen. Three days after the cessation of
      bupropion, his delirious condition gradually improved. Duloxetine and bupropion
      are both cytochrome P450 2D6 inhibitors that may result in a higher level of
      hydroxybupropion. An increased level of hydroxybupropion may cause the elevation
      of dopamine and a risk of subsequent delirium. We should be aware of the risk of
      delirium induced by drug-drug interactions.

PMID- 27046220
TI  - A theoretical study on superalkali-doped nanocages: unique inorganic electrides
      with high stability, deep-ultraviolet transparency, and a considerable nonlinear
      optical response.
AB  - By doping an Al12N12 nanocage with superalkali Li3O, a series of Li3O@Al12N12
      compounds were theoretically designed and investigated for the first time.
      Computational results reveal that these species contain diffuse excess electrons,
      and thus can be regarded as inorganic electrides of a new type. As expected,
      these proposed electrides possess considerable first hyperpolarizabilities
      (beta0) up to 1.86 * 10(7) au. In particular, the lowest-energy Li3O@Al12N12
      exhibits high stability and excellent deep-ultraviolet transparency. Moreover,
      the effects of superalkali and nanocage subunits on the NLO responses of
      M3O@Al12N12 (M = Li, Na, K) and Li3O@X12Y12 (X = B, Al; Y = N, P) are
      systemically investigated. Results show that the respective substitution of Na3O
      and B12P12 for Li3O and Al12N12 can bring a larger beta0 for such electrides.
      This study may be significant in terms of providing an effective strategy to
      design thermally stable inorganic electrides as potential high-performance NLO
      molecules.

PMID- 27046221
TI  - Geniposide Protects Primary Cortical Neurons against Oligomeric Abeta1-42-Induced
      Neurotoxicity through a Mitochondrial Pathway.
AB  - Mitochondrial dysfunction plays a key role in the progression of Alzheimer's
      disease (AD). The accumulation of amyloid-beta peptide (Abeta) in the brains of
      AD patients is thought to be closely related to neuronal mitochondrial
      dysfunction and oxidative stress. Therefore, protecting mitochondria from Abeta
      induced neurotoxicity is an effective strategy for AD therapeutics. In a previous
      study, we found that geniposide, a pharmacologically active compound purified
      from gardenia fruit, has protective effects on oxidative stress and mitochondrial
      dysfunction in AD transgenic mouse models. However, whether geniposide has a
      protective effect on Abeta-induced neuronal dysfunction remains unknown. In the
      present study, we demonstrate that geniposide protects cultured primary cortical
      neurons from Abeta-mediated mitochondrial dysfunction by recovering ATP
      generation, mitochondrial membrane potential (MMP), and cytochrome c oxidase
      (CcO) and caspase 3/9 activity; by reducing ROS production and cytochrome c
      leakage; as well as by inhibiting apoptosis. These findings suggest that
      geniposide may attenuate Abeta-induced neuronal injury by inhibiting
      mitochondrial dysfunction and oxidative stress. 

PMID- 27046223
TI  - Roles of hesC and gcm in echinoid larval mesenchyme cell development.
AB  - To understand the roles of hesC and gcm during larval mesenchyme specification
      and differentiation in echinoids, we performed perturbation experiments for these
      genes in two distantly related euechinoids, Hemicentrotus pulcherrimus and
      Scaphechinus mirabilis. The number of larval mesenchyme cells increased when the
      translation of hesC was inhibited, thereby suggesting that hesC has a general
      role in larval mesenchyme development. We confirmed previous results by
      demonstrating that gcm is involved in pigment cell differentiation. Simultaneous
      inhibition of the translation of hesC and gcm induced a significant increase in
      the number of skeletogenic cells, which suggests that gcm functions in
      skeletogenic fate repression. Based on these observations, we suggest that: (i)
      hesC participates in some general aspects of mesenchymal cell development; and
      (ii) gcm is involved in the mechanism responsible for the binary specification of
      skeletogenic and pigment cell fates. 

PMID- 27046224
TI  - Enantioselective Total Synthesis of Fluvirucinin B1.
AB  - A convergent synthesis of fluvirucinin B1 from acid ent-6a and nitrile ent-9,
      involving an organocopper coupling, a stereoselective allylation, a ring-closing
      metathesis reaction, and a stereoselective hydrogenation as the key steps, is
      reported. The starting building blocks have been prepared in a straightforward
      manner from a common phenylglycinol-derived lactam 1. An unprecedented
      regioselective oxidation of phenylglycinol-derived secondary amines 5 to
      carboxylic acids 6 has been developed. 

PMID- 27046222
TI  - A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and
      Risk of Colorectal Cancer in the European Prospective Investigation into Cancer
      and Nutrition (EPIC).
AB  - BACKGROUND: Obesity is positively associated with colorectal cancer. Recently,
      body size subtypes categorised by the prevalence of hyperinsulinaemia have been
      defined, and metabolically healthy overweight/obese individuals (without
      hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular
      disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese
      counterparts. Whether similarly variable relationships exist for metabolically
      defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND
      FINDINGS: The association of metabolically defined body size phenotypes with
      colorectal cancer was investigated in a case-control study nested within the
      European Prospective Investigation into Cancer and Nutrition (EPIC) study.
      Metabolic health/body size phenotypes were defined according to hyperinsulinaemia
      status using serum concentrations of C-peptide, a marker of insulin secretion. A
      total of 737 incident colorectal cancer cases and 737 matched controls were
      divided into tertiles based on the distribution of C-peptide concentration
      amongst the control population, and participants were classified as metabolically
      healthy if below the first tertile of C-peptide and metabolically unhealthy if
      above the first tertile. These metabolic health definitions were then combined
      with body mass index (BMI) measurements to create four metabolic health/body size
      phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2),
      (2) metabolically healthy/overweight (BMI >= 25 kg/m2), (3) metabolically
      unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically
      unhealthy/overweight (BMI >= 25 kg/m2). Additionally, in separate models, waist
      circumference measurements (using the International Diabetes Federation cut
      points [>=80 cm for women and >=94 cm for men]) were used (instead of BMI) to
      create the four metabolic health/body size phenotype categories. Statistical
      tests used in the analysis were all two-sided, and a p-value of <0.05 was
      considered statistically significant. In multivariable-adjusted conditional
      logistic regression models with BMI used to define adiposity, compared with
      metabolically healthy/normal weight individuals, we observed a higher colorectal
      cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59,
      95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01
      1.94) participants, but not among metabolically healthy/overweight individuals
      (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal
      cancer risk was observed for metabolically healthy/overweight individuals
      compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI
      0.49-0.96). These associations were generally consistent when waist circumference
      was used as the measure of adiposity. To our knowledge, there is no universally
      accepted clinical definition for using C-peptide level as an indication of
      hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the
      classification of individuals as being hyperinsulinaemic-based on their C-peptide
      level-was arbitrary. However, when we used quartiles or the median of C-peptide,
      instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of
      associations was observed. CONCLUSIONS: These results support the idea that
      individuals with the metabolically healthy/overweight phenotype (with normal
      insulin levels) are at lower colorectal cancer risk than those with
      hyperinsulinaemia. The combination of anthropometric measures with metabolic
      parameters, such as C-peptide, may be useful for defining strata of the
      population at greater risk of colorectal cancer.

PMID- 27046225
TI  - Combined AKT and MEK Pathway Blockade in Pre-Clinical Models of Enzalutamide
      Resistant Prostate Cancer.
AB  - Despite recent improvements in patient outcomes using newer androgen receptor
      (AR) pathway inhibitors, treatment resistance in castrate resistant prostate
      cancer (CRPC) continues to remain a clinical problem. Co-targeting alternate
      resistance pathways are of significant interest to treat CRPC and delay the onset
      of resistance. Both the AKT and MEK signaling pathways become activated as
      prostate cancer develops resistance to AR-targeted therapies. This pre-clinical
      study explores co-targeting these pathways in AR-positive prostate cancer models.
      Using various in vitro models of prostate cancer disease states including
      androgen dependent (LNCaP), CRPC (V16D and 22RV1) and ENZ-resistant prostate
      cancer (MR49C and MR49F), we evaluate the relevance of targeting both AKT and MEK
      pathways. Our data reveal that AKT inhibition induces apoptosis and inhibits cell
      growth in PTEN null cell lines independently of their sensitivity to hormone
      therapy; however, AKT inhibition had no effect on the PTEN positive 22RV1 cell
      line. Interestingly, we found that MEK inhibition had greater effect on 22RV1
      cells compared to LNCaP, V16D or ENZ-resistant cells MR49C and MR49F cells. In
      vitro, combination AKT and MEK blockade had evidence of synergy observed in some
      cell lines and assays, but this was not consistent across all results. In vivo,
      the combination of AKT and MEK inhibition resulted in more consistent tumor
      growth inhibition of MR49F xenografts and longer disease specific survival
      compared to AKT inhibitor monotherapy. As in our in vitro study, 22RV1 xenografts
      were more resistant to AKT inhibition while they were more sensitive to MEK
      inhibition. Our results suggest that targeting AKT and MEK in combination may be
      a valuable strategy in prostate cancer when both pathways are activated and
      further support the importance of characterizing the dominant oncogenic pathway
      in each patient's tumor in order to select optimal therapy. 

PMID- 27046226
TI  - Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using
      Human Skin Models.
AB  - Tissue dehydration results in three major types of exsiccosis--hyper-, hypo-, or
      isonatraemia. All three types entail alterations of salt concentrations leading
      to impaired biochemical processes, and can finally cause severe morbidity. The
      aim of our study was to demonstrate the feasibility of a microwave-based sensor
      technology for the non-invasive measurement of the hydration status.
      Electromagnetic waves at high frequencies interact with molecules, especially
      water. Hence, if a sample contains free water molecules, this can be detected in
      a reflected microwave signal. To develop the sensor system, human three
      dimensional skin equivalents were instituted as a standardized test platform
      mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a
      specific hydration and density of matrix components were generated and microwave
      measurements were performed. Hydration-specific spectra allowed deriving the
      hydration state of the skin models. A further advantage of the skin equivalents
      was the characterization of the impact of distinct skin components on the
      measured signals to investigate mechanisms of signal generation. The results
      demonstrate the feasibility of a non-invasive microwave-based hydration sensor
      technology. The sensor bears potential to be integrated in a wearable medical
      device for personal health monitoring.

PMID- 27046228
TI  - Infective endocarditis due to Abiotrophia defectiva and Granulicatella spp.
      complicated by infectious intracranial cerebral aneurysms: a report of three
      cases and review of the literature.
AB  - Nutritionally variant streptococci, now classified as Abiotrophia defectivaor
      Granulicatella spp., are thought to account for 2 % of all infective endocarditis
      cases but estimates of their frequency are complicated by changes in nomenclature
      and difficulties in obtaining positive microbiology cultures. Their growth
      characteristics and difficulty undertaking antibiotic susceptibility testing may
      impede optimal antibiotic treatment decisions. We describe three patients with
      definite infective endocarditis due to these organisms seen at our hospital
      between 2005 and 2010, all of whom presented with neurological symptoms due to
      infectious intracranial cerebral aneurysms. We recommend that, for patients with
      left-sided infective endocarditis due to A. defictiva and Granulicatella spp.,
      clinicians should consider imaging the central nervous system. 

PMID- 27046227
TI  - Sialylation converts arthritogenic IgG into inhibitors of collagen-induced
      arthritis.
AB  - Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated
      protein antibodies (ACPAs) have diverse glycosylation variants; however, key
      sugar chains modulating the arthritogenic activity of IgG remain to be clarified.
      Here, we show that reduced sialylation is a common feature of RA-associated IgG
      in humans and in mouse models of arthritis. Genetically blocking sialylation in
      activated B cells results in exacerbation of joint inflammation in a collagen
      induced arthritis (CIA) model. On the other hand, artificial sialylation of anti
      type II collagen antibodies, including ACPAs, not only attenuates arthritogenic
      activity, but also suppresses the development of CIA in the antibody-infused
      mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data
      demonstrate that sialylation levels control the arthritogenicity of RA-associated
      IgG, presenting a potential target for antigen-specific immunotherapy. 

PMID- 27046229
TI  - Oxidative Deamination of Serum Albumins by (-)-Epigallocatechin-3-O-Gallate: A
      Potential Mechanism for the Formation of Innate Antigens by Antioxidants.
AB  - (-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant polyphenol in green
      tea, mediates the oxidative modification of proteins, generating protein
      carbonyls. However, the underlying molecular mechanism remains unclear. Here we
      analyzed the EGCG-derived intermediates generated upon incubation with the human
      serum albumin (HSA) and established that EGCG selectively oxidized the lysine
      residues via its oxidative deamination activity. In addition, we characterized
      the EGCG-oxidized proteins and discovered that the EGCG could be an endogenous
      source of the electrically-transformed proteins that could be recognized by the
      natural antibodies. When HSA was incubated with EGCG in the phosphate-buffered
      saline (pH 7.4) at 37 degrees C, the protein carbonylation was associated with
      the formation of EGCG-derived products, such as the protein-bound EGCG, oxidized
      EGCG, and aminated EGCG. The aminated EGCG was also detected in the sera from the
      mice treated with EGCG in vivo. EGCG selectively oxidized lysine residues at the
      EGCG-binding domains in HSA to generate an oxidatively deaminated product,
      aminoadipic semialdehyde. In addition, EGCG treatment results in the increased
      negative charge of the protein due to the oxidative deamination of the lysine
      residues. More strikingly, the formation of protein carbonyls by EGCG markedly
      increased its cross-reactivity with the natural IgM antibodies. These findings
      suggest that many of the beneficial effects of EGCG may be partly attributed to
      its oxidative deamination activity, generating the oxidized proteins as a target
      of natural antibodies. 

PMID- 27046230
TI  - Novel benzylidenephenylpyrrolizinones with pleiotropic activities potentially
      useful in Alzheimer's disease treatment.
AB  - This work describes the synthesis and the biological evaluation of novel
      benzylidenephenylpyrrolizinones as potential antioxidant, metal chelating or
      amyloid beta (betaA) aggregation inhibitors. Some derivatives exhibited
      interesting results in regard to several of the performed evaluations and appear
      as valuable Multi-Target Directed Ligands with potential therapeutic interest in
      Alzheimer's disease. Among them, compound 29 particularly appears as a valuable
      radical and NO scavenger, a Cu(II) and Fe(II) chelating agent and exhibits
      moderate betaA aggregation inhibition properties. These activities, associated to
      a good predictive bioavailability and a lack of cytotoxicity, design it as a
      promising hit for further in vivo investigation.

PMID- 27046231
TI  - Mono- and tetra-substituted zinc(II) phthalocyanines containing morpholinyl
      moieties: Synthesis, antifungal photodynamic activities, and structure-activity
      relationships.
AB  - A series of zinc(II) phthalocyanines (ZnPcs) mono-substituted and tetra
      substituted with morpholinyl moieties and their quaternized derivatives have been
      synthesized and evaluated for their antifungal photodynamic activities toward
      Candida albicans. The alpha-substituted, quaternized, and mono-substituted ZnPcs
      are found to have higher antifungal photoactivity than beta-substituted, neutral,
      and tetra-substituted counterparts. The cationic alpha-mono-substituted ZnPc (6a)
      exhibits the highest photocytotoxicity. Moreover, it is more potent than axially
      di-substituted analogue. The different photocytotoxicities of these compounds
      have also been rationalized by investigating their spectroscopic and
      photochemical properties, aggregation trend, partition coefficients, and cellular
      uptake. The IC90 value of 6a against C. albicans cells is as low as 3.3 MUM with
      a light dose of 27 J cm(-2), meaning that 6a is a promising candidate as the
      antifungal photosensitizer for future investigations. 

PMID- 27046232
TI  - Consciousness fluctuation during general anesthesia: a theoretical approach to
      anesthesia awareness and memory modulation.
AB  - With anesthesia awareness as a model of study we debate the both fascinating and
      dangerous phenomenon called consciousness fluctuation that takes place during
      surgical anesthesia. In accordance with current scientific knowledge this paradox
      is the consequence of our limits in both precise knowledge of anesthesia
      mechanisms and our inability to accurately assess the level of anesthesia with
      brain monitoring. We also focus on the relationships between memory and
      anesthesia, as well as the possibility of interfering with memory during general
      anesthesia.

PMID- 27046233
TI  - Investing in organisational culture: nursing students' experience of
      organisational learning culture in aged care settings following a program of
      cultural development.
AB  - BACKGROUND: Concerns around organisational learning culture limit nursing student
      placements in aged care settings to first year experiences. AIM: Determine the
      impact of an extended staff capacity building program on students' experiences of
      the organisational learning culture in the aged care setting. DESIGN: Pre and
      post-test design. METHODS: A convenience sample of first, second and third year
      Bachelor of Nursing students attending placements at three residential aged care
      facilities completed the Clinical Learning Organisational Culture Survey.
      Responses between the group that attended placement before the program (n =
      17/44; RR 38%) and the group that attended following the program (n = 33/72; RR
      45%) were compared. RESULTS: Improvements were noted in the areas of recognition,
      accomplishment, and influence, with decreases in dissatisfaction. CONCLUSION:
      Organisational investment in building staff capacity can produce a positive
      learning culture. The aged care sector offers a rich learning experience for
      students when staff capacity to support learning is developed.

PMID- 27046234
TI  - Why Are Some Population Interventions for Diet and Obesity More Equitable and
      Effective Than Others? The Role of Individual Agency.
AB  - Jean Adams and colleagues argue that population interventions that require
      individuals to use a low level of agency to benefit are likely to be most
      effective and most equitable.

PMID- 27046235
TI  - Male Lineages in Brazil: Intercontinental Admixture and Stratification of the
      European Background.
AB  - The non-recombining nature of the Y chromosome and the well-established phylogeny
      of Y-specific Single Nucleotide Polymorphisms (Y-SNPs) make them useful for
      defining haplogroups with high geographical specificity; therefore, they are more
      apt than the Y-STRs to detect population stratification in admixed populations
      from diverse continental origins. Different Y-SNP typing strategies have been
      described to address issues of population history and movements within geographic
      territories of interest. In this study, we investigated a set of 41 Y-SNPs in
      1217 unrelated males from the five Brazilian geopolitical regions, aiming to
      disclose the genetic structure of male lineages in the country. A population
      comparison based on pairwise FST genetic distances did not reveal statistically
      significant differences in haplogroup frequency distributions among populations
      from the different regions. The genetic differences observed among regions were,
      however, consistent with the colonization history of the country. The sample from
      the Northern region presented the highest Native American ancestry (8.4%),
      whereas the more pronounced African contribution could be observed in the
      Northeastern population (15.1%). The Central-Western and Southern samples showed
      the higher European contributions (95.7% and 93.6%, respectively). The
      Southeastern region presented significant European (86.1%) and African (12.0%)
      contributions. The subtyping of the most frequent European lineage in Brazil
      (R1b1a-M269) allowed differences in the genetic European background of the five
      Brazilian regions to be investigated for the first time. 

PMID- 27046236
TI  - Chlamydia trachomatis infection prevalence and serovar distribution in a high
      density urban area in the north of Italy.
AB  - The aim of this study was to assess Chlamydia trachomatis (CT) infection
      prevalence and serovar distribution in a high-density urban area in the north of
      Italy, by comparing different groups of subjects divided on the basis of the type
      of care provider they referred to (STI Clinic, gynaecologists or general
      practitioners). From January 2011 to May 2014, all the specimens submitted to the
      Microbiology Laboratory of St Orsola Hospital in Bologna for CT detection were
      tested by PCR assay. For positive specimens, molecular genotyping based on RFLP
      analysis was performed. Total prevalence of CT infection was 8.1 %, with
      significant differences between subgroups (P<0.01) but stable during the study
      period. The STI Clinic was mainly responsible for CT diagnosis, whereas the
      lowest infection prevalence was detected in gynaecological clinics, despite the
      high number of tests performed. Extra-genital samples were almost exclusively
      collected from males at the STI Clinic. Interestingly, 13.3 % of patients
      providing extra-genital specimens were positive for CT on rectal and/or
      pharyngeal swabs, and 4.4 % of cases would have been missed if extra-genital
      sites had not been tested. The most common serovar was E, and serovar
      distribution was influenced by gender (P<0.01), age (P<0.01), care provider
      (P=0.01) and anatomical site (P<0.01). The L2 serovar was detected only in extra
      genital samples from males at the STI Clinic. Knowledge about care providers'
      contributions in CT testing and diagnosis is essential for infection control. CT
      typing is crucial for appropriate management of specific infections, such as
      lymphogranuloma venereum in extra-genital samples of high-risk populations. 

PMID- 27046237
TI  - Predator-prey dynamics stabilised by nonlinearity explain oscillations in dust
      forming plasmas.
AB  - Dust-forming plasmas are ionised gases that generate particles from a precursor.
      In nature, dust-forming plasmas are found in flames, the interstellar medium and
      comet tails. In the laboratory, they are valuable in generating nanoparticles for
      medicine and electronics. Dust-forming plasmas exhibit a bizarre, even puzzling
      behaviour in which they oscillate with timescales of seconds to minutes. Here we
      show how the problem of understanding these oscillations may be cast as a
      predator-prey problem, with electrons as prey and particles as predators. The
      addition of a nonlinear loss term to the classic Lotka-Volterra equations used
      for describing the predator-prey problem in ecology not only stabilises the
      oscillations in the solutions for the populations of electrons and particles in
      the plasma but also explains the behaviour in more detail. The model explains the
      relative phase difference of the two populations, the way in which the frequency
      of the oscillations varies with the concentration of the precursor gas, and the
      oscillations of the light emission, determined by the populations of both
      species. Our results demonstrate the value of adopting an approach to a complex
      physical science problem that has been found successful in ecology, where
      complexity is always present. 

PMID- 27046238
TI  - Falling Victim to Wasps in the Air: A Fate Driven by Prey Flight Morphology?
AB  - In prey-predator systems where the interacting individuals are both fliers, the
      flight performance of both participants heavily influences the probability of
      success of the predator (the prey is captured) and of the prey (the predator is
      avoided). While the flight morphology (an estimate of flight performance) of
      predatory wasps has rarely been addressed as a factor that may contribute to
      explain prey use, how the flight morphology of potential prey influences the
      output of predator-prey encounters has not been studied. Here, we hypothesized
      that flight morphology associated with flight ability (flight muscle mass to body
      mass ratio (FMR) and body mass to wing area ratio (wing loading, WL)) of Diptera
      affect their probability of being captured by specialized Diptera-hunting wasps
      (Bembix merceti and B. zonata), predicting a better manoeuvrability and
      acceleration capacity achieved by higher FMR and lower WL, and flight speed
      achieved by higher WL. In addition, wasp species with better flight morphology
      should be less limited by an advantageous Diptera flight morphology. Overall, the
      abundance of dipterans in the environment explained an important part of the
      observed variance in prey capture rate. However, it was not the only factor
      shaping prey capture. First, higher prey abundance was associated with greater
      capture rate for one species (B. merceti), although not for the other one.
      Second, the interaction observed between the environmental dipteran availability
      and dipteran WL for B. zonata suggests that greater dipteran WL (this probably
      meaning high cruising speed) decreased the probability of being captured, as long
      as fly abundance was high in the environment. Third, greater dipteran FMR (which
      likely means high manoeuvrability and acceleration capacity) helped to reduce
      predation by B. merceti if, again, dipterans were abundant in the environment.
      Wasp WL only varied with body mass but not between species, thereby hardly
      accounting for inter-specific differences in the wasps' predatory patterns.
      However, the greater FMR of B. zonata, which implies better flight performance
      and greater load-lifting capacity, may explain why the capture rate in the two
      wasp species is affected by different factor interactions. In conclusion,
      although prey availability remains the primary factor shaping prey use, prey
      flight morphology seems to gain an additional role under conditions of abundant
      prey, when wasps can avoid flies with better flight ability. 

PMID- 27046239
TI  - Norovirus Infection: Replication, Manipulation of Host, and Interaction with the
      Host Immune Response.
AB  - Noroviruses (NoVs) belong to the Caliciviridae family of viruses and are
      responsible for causing the majority of gastroenteritis outbreaks worldwide. In
      the past decade, research on NoV biology has intensified because of the discovery
      of murine NoV and subsequently the first cell culture system and small animal
      model for NoV replication and pathogenesis. In this review, we discuss the
      current literature on NoV biology, focusing particularly on NoV replication and
      the interaction between NoV and the host immune response. Understanding the NoV
      replication cycle and its interaction with cellular processes and innate immune
      immunity will help develop molecular targets to control human NoV infection and
      prevent outbreaks. In addition to the innate immune response, we have documented
      the current efforts to develop NoV vaccines to control outbreaks. 

PMID- 27046240
TI  - The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis.
AB  - Despite the fact that Candida albicans is an important human fungal pathogen and
      Dectin-2 is a major pattern recognition receptor for fungi, our knowledge
      regarding the role of Dectin-2 for the host defense against disseminated
      candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more
      susceptible to systemic candidiasis, and the susceptibility was mirrored by an
      elevated fungal load in the kidneys that correlated with the presence of large
      inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin
      2 receptor was moderately decreased, while production of most of the macrophage
      derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was
      decreased. No striking differences among several Candida mutants defective in
      mannans could be detected between naive wild-type and Dectin-2(-/-) mice, apart
      from the beta-mannan-deficient bmt1Delta/bmt2Delta/bmt5Delta triple mutant,
      suggesting that beta-mannan may partially mask alpha-mannan detection, which is
      the major fungal structure recognized by Dectin-2. Deciphering the mechanisms
      responsible for host defense against the majority of C. albicans strains
      represents an important step in understanding the pathophysiology of systemic
      candidiasis, which might lead to the development of novel immunotherapeutic
      strategies. 

PMID- 27046241
TI  - Age-Adjusted Cutoff D-Dimer Level to Rule Out Acute Pulmonary Embolism: A
      Validation Cohort Study.
AB  - BACKGROUND: The diagnosis of pulmonary embolism in the Emergency Room setting is
      challenging. Multiple patients have to undergo radiologic assessment with its
      inherent shortcomings. The D-dimer test with accepted cutoff level of 500 MUg/L
      is associated with a high proportion of false-positive results. The present study
      aimed to validate the advantages of using an age-adjusted D-dimer cutoff level,
      compared with 500-MUg/L value in the diagnosis of acute pulmonary embolism.
      METHODS: This study evaluated patients admitted to the Rambam Emergency Room
      between 2011 and 2014 with a suspected diagnosis of pulmonary embolism. Patient
      data, D-dimer plasma levels, and imaging results were collected. The study cohort
      was subdivided according to the D-dimer levels below and above 500 MUg/L. The
      group with levels above 500 MUg/L was further assessed using the newly suggested
      age-adjusted D-dimer cutoff level, defined as age multiplied by 10. RESULTS:
      Files of 1241 patients were reviewed; 654 patients with low or intermediate risk
      for pulmonary embolism had a D-dimer level above 500 MUg/L. Two hundred eight
      (208) patients had a D-dimer level above 500 MUg/L but below the age-adjusted
      cutoff value; one of them was diagnosed with pulmonary embolism (0.48% [95%
      confidence interval 0%-2.6%]). Four hundred forty-six (446) patients had a D
      dimer level above the age-adjusted cutoff value, and 28 of them were diagnosed
      with pulmonary embolism (6.28% [95% confidence interval 4.2%-8.9%]), representing
      a negative predictive value of 99.5% for the age-adjusted cutoff level.
      CONCLUSIONS: An age-adjusted D-dimer cutoff level may be safely used to exclude
      pulmonary embolism in patients with a low or intermediate probability for acute
      pulmonary embolism, alleviating the need to perform unnecessary imaging
      evaluations.

PMID- 27046242
TI  - Treatment of Basal Cell Carcinoma in the Elderly: What Nondermatologists Need to
      Know.
AB  - As the population ages and incidence of basal cell carcinoma continues to
      increase, we will be faced more frequently with difficult treatment decisions for
      basal cell carcinoma in the elderly. Different treatment options, including
      surgical excision, electrodessication and curettage, cryosurgery, imiquimod,
      photodynamic therapy, 5-fluorouracil, radiation therapy, vismodegib, combination
      therapy, and observation, may be considered on the basis of tumor
      characteristics. Given the wide range of therapeutic options, treatments can be
      tailored to achieve patients' goals of care within their anticipated life
      expectancy.

PMID- 27046243
TI  - Update in Outpatient General Internal Medicine: Practice-Changing Evidence
      Published in 2015.
AB  - Identifying new practice-changing articles is challenging. To determine the 2015
      practice-changing articles most relevant to outpatient general internal medicine,
      3 internists independently reviewed the titles and abstracts of original
      articles, synopses of single studies and syntheses, and databases of syntheses.
      For original articles, internal medicine journals with the 7 highest impact
      factors were reviewed: New England Journal of Medicine, Lancet, Journal of the
      American Medical Association (JAMA), British Medical Journal, Public Library of
      Science Medicine, Annals of Internal Medicine, and JAMA Internal Medicine. For
      synopses of single studies and syntheses, collections in American College of
      Physicians Journal Club, Journal Watch, and Evidence-Based Medicine were
      reviewed. For databases of synthesis, Evidence Updates and the Cochrane Library
      were reviewed. More than 100 articles were identified. Criteria for inclusion
      were as follows: clinical relevance, potential for practice change, and strength
      of evidence. Clusters of important articles around one topic were considered as a
      single-candidate series. The 5 authors used a modified Delphi method to reach
      consensus on inclusion of 7 topics for in-depth appraisal.

PMID- 27046244
TI  - A Precarious Presentation: Systemic Lupus Erythematosus.

PMID- 27046245
TI  - A Blend of Sesame and Rice Bran Oils Lowers Hyperglycemia and Improves the
      Lipids.
AB  - BACKGROUND: Considering the health benefits of sesame oil and rice bran oil, the
      study was conducted to determine the extent to which the daily use of this blend
      of oils controls hyperglycemia and improves the lipid profile. METHODS: In this 8
      week open-label randomized dietary intervention study, 300 type 2 diabetes
      mellitus patients and 100 normoglycemic subjects were grouped as 1) normoglycemic
      subjects (n = 100) treated with sesame oil blend Vivo (Adani Wilmar, Ahmedabad,
      Gujarat, India), 2) type 2 diabetes mellitus patients treated with sesame oil
      blend (n = 100), 3) type 2 diabetes mellitus patients treated with glibenclamide
      (n = 100; 5 mg/d), and 4) type 2 diabetes mellitus patients treated in
      combination of glibenclamide (5 mg/d) and sesame oil blend (n = 100). Twelve-hour
      fasting blood glucose, glycated hemoglobin (HbA1c), and lipid profile followed by
      postprandial blood glucose were measured at baseline. Sesame oil blend was
      supplied to the respective groups, who were instructed to use as cooking oil for
      8 weeks. Fasting and postprandial blood glucose was measured at week 4 and week
      8, while HbA1c and lipid profile were measured at week 8. RESULTS: At week 4 and
      week 8, type 2 diabetes mellitus patients treated with sesame oil blend or
      glibenclamide or combination of glibenclamide and sesame oil blend showed
      significant reduction of fasting and postprandial blood glucose (P <.001). HbA1c,
      total cholesterol, triglycerides, low-density lipoprotein cholesterol, and non
      high-density lipoprotein cholesterol were significantly reduced (P <.001), while
      high-density lipoprotein cholesterol was significantly increased at week 8 (P
      <.001) in type 2 diabetes mellitus patients treated with the sesame oil blend or
      combination of glibenclamide and sesame oil blend; whereas glibenclamide-alone
      treated type 2 diabetes mellitus patients showed a significant reduction of HbA1c
      (P <.001) only. CONCLUSIONS: A novel blend of 20% cold-pressed unrefined sesame
      oil and 80% physically refined rice bran oil as cooking oil, lowered
      hyperglycemia and improved the lipid profile in type 2 diabetes mellitus
      patients.

PMID- 27046246
TI  - An Unusual Rapid Response Call: Malignant Catatonia.

PMID- 27046247
TI  - Monitoring for Pulmonary Hypertension Following Pulmonary Embolism: The INFORM
      Study.
AB  - BACKGROUND: Pulmonary hypertension and chronic thromboembolic pulmonary
      hypertension may develop after a pulmonary embolism event. A ventilation
      perfusion scan is recommended as a first-line modality for suspected chronic
      thromboembolic pulmonary hypertension. In this study, we determined the
      prevalence of pulmonary hypertension following incident pulmonary embolism and
      the disease-monitoring patterns in this population. METHODS: We conducted a
      retrospective claims database analysis of incident pulmonary embolism cases (July
      1, 2010 to September 30, 2011) and extracted data for 1 year prior to and 2 years
      after the incident pulmonary embolism event. Data were analyzed for diagnoses and
      symptoms related to pulmonary hypertension, claims consistent with other heart or
      lung diseases, diagnostic imaging tests, and time to first diagnostic imaging
      test post pulmonary embolism. RESULTS: Of the 7068 incident pulmonary embolism
      patients that met eligibility criteria, 87% had a claim for a pulmonary
      hypertension-related symptom and 7.6% had a claim for pulmonary hypertension
      during follow-up. Only 55% of all pulmonary embolism patients had diagnostic
      procedural claim(s) post pulmonary embolism: echocardiogram, 47%; computed
      tomographic angiography, 20%; ventilation-perfusion scan, 6%; and right heart
      catheterization or pulmonary angiography, <1%. The mean time from pulmonary
      embolism diagnosis to first screening test was 131 days. CONCLUSIONS: Despite
      exhibiting pulmonary hypertension-related symptoms, many pulmonary embolism
      patients did not undergo imaging tests that could diagnose pulmonary hypertension
      or chronic thromboembolic pulmonary hypertension. This study suggests that
      physician education about the risk of pulmonary hypertension and chronic
      thromboembolic pulmonary hypertension after pulmonary embolism may need to be
      improved.

PMID- 27046248
TI  - Seeking punctuation clarity--that is, the proper use of the hyphen and dashes-
      for publishing in Autophagy.

PMID- 27046249
TI  - The BECN1 N-terminal domain is intrinsically disordered.
AB  - BECN1/Beclin 1 has a critical role in the early stages of autophagosome
      formation. Recently, structures of its central and C-terminal domains were
      reported, however, little structural information is available on the N-terminal
      domain, comprising a third of the protein. This lack of structural information
      largely stems from the inability to produce this region in a purified form. Here,
      we describe the expression and purification of the N-terminal domain of BECN1
      (residues 1 to 150) and detailed biophysical characterization, including NMR
      spectroscopy. Combined, our studies demonstrated at the atomic level that the
      BECN1 N-terminal domain is intrinsically disordered, and apart from the BH3
      subdomain, remains disordered following interaction with a binding partner,
      BCL2L1/BCL-XL. In addition, the BH3 domain alpha-helix induced upon interaction
      with BCL2L1 reverts to a disordered state when the complex is dissociated by
      exposure to a competitive inhibitor. No significant interactions between N- and C
      terminal domains were detected. 

PMID- 27046250
TI  - The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery
      via binding and phosphorylating ATG14.
AB  - ULK1 (unc-51 like autophagy activating kinase 1), the key mediator of MTORC1
      signaling to autophagy, regulates early stages of autophagosome formation in
      response to starvation or MTORC1 inhibition. How ULK1 regulates the autophagy
      induction process remains elusive. Here, we identify that ATG13, a binding
      partner of ULK1, mediates interaction of ULK1 with the ATG14-containing
      PIK3C3/VPS34 complex, the key machinery for initiation of autophagosome
      formation. The interaction enables ULK1 to phosphorylate ATG14 in a manner
      dependent upon autophagy inducing conditions, such as nutrient starvation or
      MTORC1 inhibition. The ATG14 phosphorylation mimics nutrient deprivation through
      stimulating the kinase activity of the class III phosphatidylinositol 3-kinase
      (PtdIns3K) complex and facilitates phagophore and autophagosome formation. By
      monitoring the ATG14 phosphorylation, we determined that the ULK1 activity
      requires BECN1/Beclin 1 but not the phosphatidylethanolamine (PE)-conjugation
      machinery and the PIK3C3 kinase activity. Monitoring the phosphorylation also
      allowed us to identify that ATG9A is required to suppress the ULK1 activity under
      nutrient-enriched conditions. Furthermore, we determined that ATG14
      phosphorylation depends on ULK1 and dietary conditions in vivo. These results
      define a key molecular event for the starvation-induced activation of the ATG14
      containing PtdIns3K complex by ULK1, and demonstrate hierarchical relations
      between the ULK1 activation and other autophagy proteins involved in phagophore
      formation. 

PMID- 27046252
TI  - The ins and outs of reticulocyte maturation revisited: The role of autophagy in
      sickle cell disease.
AB  - Autophagy plays an important role in the removal of membrane bound organelles
      during the last stage of erythropoiesis as the enucleate reticulocyte matures
      into the erythrocyte. Autophagic vesicles are expelled from the reticulocyte as
      intact, inside-out, phosphatidylserine (PS) decorated vesicles and are
      subsequently removed during splenic passage. Failure to remove these vesicles
      causes the elevation in PS exposed red cells in Sickle Cell Disease. 

PMID- 27046251
TI  - Lysosomal putative RNA transporter SIDT2 mediates direct uptake of RNA by
      lysosomes.
AB  - Lysosomes are thought to be the major intracellular compartment for the
      degradation of macromolecules. We recently identified a novel type of autophagy,
      RNautophagy, where RNA is directly taken up by lysosomes in an ATP-dependent
      manner and degraded. However, the mechanism of RNA translocation across the
      lysosomal membrane and the physiological role of RNautophagy remain unclear. In
      the present study, we performed gain- and loss-of-function studies with isolated
      lysosomes, and found that SIDT2 (SID1 transmembrane family, member 2), an
      ortholog of the Caenorhabditis elegans putative RNA transporter SID-1 (systemic
      RNA interference deficient-1), mediates RNA translocation during RNautophagy. We
      also observed that SIDT2 is a transmembrane protein, which predominantly
      localizes to lysosomes. Strikingly, knockdown of Sidt2 inhibited up to ~50% of
      total RNA degradation at the cellular level, independently of macroautophagy.
      Moreover, we showed that this impairment is mainly due to inhibition of lysosomal
      RNA degradation, strongly suggesting that RNautophagy plays a significant role in
      constitutive cellular RNA degradation. Our results provide a novel insight into
      the mechanisms of RNA metabolism, intracellular RNA transport, and atypical types
      of autophagy. 

PMID- 27046253
TI  - Another DRAM involved in autophagy and cell death.
AB  - Macroautophagy (hereafter referred to as autophagy) is controlled by a number of
      core proteins that are critical for all autophagy responses. In addition, a
      number of autophagy regulators have been found that are not critical for
      macroautophagy per se, but which play roles in regulating autophagy in either
      selective situations or in response to specific stimuli. In a recent study, we
      reported the initial characterization of a new autophagy regulator encoded by
      TMEM150B that is related to the Damage-Regulated Autophagy Modulator, DRAM1. We
      have termed this factor DRAM3 for DRAM-Related/Associated Member 3.
      Interestingly, like DRAM1, DRAM3 regulates both autophagy and cell death, but we
      found these two functions of the protein are not intrinsically connected. 

PMID- 27046254
TI  - Small differences make a big impact: Structural insights into the differential
      function of the 2 Atg8 homologs in C. elegans.
AB  - The 2 C. elegans homologs of Atg8, LGG-1 and LGG-2, show differential function in
      the degradation of protein aggregates during embryogenesis. LGG-1 is essential
      for the degradation of various protein aggregates, while LGG-2 has cargo-specific
      and developmental stage-specific roles. LGG-1 and LGG-2 differentially interact
      with autophagy substrates and ATG proteins. LGG-1 and LGG-2 possess 2 hydrophobic
      pockets, the W-site and the L-site, which recognize the LIR motif in Atg8-binding
      proteins. The plasticity of the W-site and the size and shape of the L-site
      differ between LGG-1 and LGG-2, thus determining their preferences for distinct
      LIR motifs. The N-terminal tails of LGG-1 and LGG-2 adopt unique closed and open
      conformations, respectively, which may result in distinct membrane tethering and
      fusion activities. LGG-1 and LGG-2 have different affinities for ATG-7 and ATG-3,
      and lipidation of LGG-2 is regulated by levels of lipidated LGG-1. Taken
      together, the structural differences between LGG-1 and LGG-2 provide insights
      into their differential functions in the aggrephagy pathway. 

PMID- 27046255
TI  - Selective autophagy gets more selective: Uncoupling of autophagy flux and
      xenophagy flux in Mycobacterium tuberculosis-infected macrophages.
AB  - Induction of autophagy has been reported as a potential means to eliminate
      intracellular pathogens. Corroborating that, many studies report inhibition of
      autophagy as a survival strategy of bacterial pathogens. Incidentally, autophagy
      at the basal level is critical for survival of host cells including macrophages.
      We asked how a bacterial pathogen could inhibit autophagy for its survival if the
      inhibition resulted in cell death. In a recent study we show distinct regulation
      of autophagy in Mycobacterium tuberculosis (Mtb)-infected macrophages where Mtb
      containing- and nonMtb-containing autophagosomes show different fates in terms of
      maturation. We show that upon Mtb infection, there is no dramatic change in the
      autophagy flux in macrophages. However, autophagosomes that contain the virulent
      strains of Mtb show selective resilience to the maturation phase of autophagy.
      Surprisingly, nonMtb-containing autophagosomes in the infected cells continue to
      mature into autolysosomes. The block in the xenophagy flux is missing in the case
      of avirulant infections. We show that this selectivity is achieved through
      selective exclusion of RAB7 from virulent Mtb-containing autophagosomes, thereby
      restricting the formation of amphisomes.

PMID- 27046256
TI  - TRANSAUTOPHAGY: European network for multidisciplinary research and translation
      of autophagy knowledge.
AB  - A collaborative consortium, named "TRANSAUTOPHAGY," has been created among
      European research groups, comprising more than 150 scientists from 21 countries
      studying diverse branches of basic and translational autophagy. The consortium
      was approved in the framework of the Horizon 2020 Program in November 2015 as a
      COST Action of the European Union (COST means: CO-operation in Science and
      Technology), and will be sponsored for 4 years. TRANSAUTOPHAGY will form an
      interdisciplinary platform for basic and translational researchers, enterprises
      and stakeholders of diverse disciplines (including nanotechnology,
      bioinformatics, physics, chemistry, biology and various medical disciplines).
      TRANSAUTOPHAGY will establish 5 different thematic working groups, formulated to
      cooperate in research projects, share ideas, and results through workshops,
      meetings and short term exchanges of personnel (among other initiatives).
      TRANSAUTOPHAGY aims to generate breakthrough multidisciplinary knowledge about
      autophagy regulation, and to boost translation of this knowledge into biomedical
      and biotechnological applications. 

PMID- 27046257
TI  - Effector proteins support the asymmetric apportioning of Salmonella during
      cytokinesis.
AB  - Salmonella-infected cells are characterized by the presence of intra-cellular
      membranous tubules that emerge from bacterial vacuoles and extend along
      microtubules. The formation of Salmonella-induced tubules depends on the
      Salmonella pathogenicity island 2-encoded type III secretion system (T3SS-2) that
      translocates bacterial effector proteins inside host cells. Effector proteins
      have enzymatic activities or allow for hijacking of cellular functions. The role
      of Salmonella-induced tubules in virulence remains unclear but their absence is
      correlated with virulence defects. This study describes the presence of inter
      cellular tubules that arise between daughter cells during cytokinesis. Inter
      cellular tubules connect bacterial vacuoles originally present in the parent cell
      and that have been apportioned between daughters. Their formation requires a
      functional T3SS-2 and effector proteins. Our data establish a correlation between
      the formation of inter-cellular tubules and the asymmetric distribution of
      bacterial vacuoles in daughters. Thus, by manipulating the distribution of
      bacteria in cytokinetic cells, Salmonella T3SS-2 effector proteins may increase
      bacterial spreading and the systemic character of the infection.

PMID- 27046259
TI  - Health Information Exchange: Perspectives From Home Healthcare.

PMID- 27046258
TI  - Molecular surveillance of nasopharyngeal carriage of Streptococcus pneumoniae in
      children vaccinated with conjugated polysaccharide pneumococcal vaccines.
AB  - Following the introduction of pneumococcal conjugate vaccines (PCVs) for infants,
      surveillance studies on Streptococcus pneumoniae carriage have proven valuable
      for monitoring vaccine effects. Here, we compared molecular versus conventional
      diagnostic methods in prospective cross-sectional surveillances in vaccinated
      infants in the Netherlands. Nasopharyngeal samples (n = 1169) from 11- and 24
      month-old children, collected during autumn/winter 2010/2011 and 2012/2013, were
      tested by conventional culture for S. pneumoniae. DNA extracted from all culture
      plate growth was tested by qPCR for pneumococcal-specific genes (lytA/piaB) and
      selected serotypes (including PCV13-serotypes). qPCR significantly increased the
      number of carriers detected compared to culture (69% vs. 57%, p < 0.0001). qPCR
      assays targeting vaccine-serotypes 4 and 5 proved non-specific (results
      excluded). For serotypes reliably targeted by qPCR, the number of serotype
      carriage events detected by qPCR (n = 709) was 1.68* higher compared to culture
      (n = 422). There was a strong correlation (rho = 0.980; p < 0.0001) between the
      number of serotypes detected using qPCR and by culture. This study demonstrates
      the high potential of molecular methods in pneumococcal surveillances,
      particularly for enhanced serotype detection. We found no evidence of a hidden
      circulation of vaccine-targeted serotypes, despite vaccine-serotypes still
      significantly contributing to invasive pneumococcal disease in unvaccinated
      individuals, supporting the presence of a substantial S. pneumoniae reservoir
      outside vaccinated children. 

PMID- 27046260
TI  - National Nurses Week 2016: Culture of Safety: It Starts With YOU.

PMID- 27046262
TI  - Graphene Monoxide Bilayer As a High-Performance on/off Switching Media for
      Nanoelectronics.
AB  - The geometries and electronic characteristics of the graphene monoxide (GMO)
      bilayer are predicted via density functional theory (DFT) calculations. All the
      possible sequences of the GMO bilayer show the typical interlayer bonding
      characteristics of two-dimensional bilayer systems with a weak van der Waals
      interaction. The band gap energies of the GMO bilayers are predicted to be
      adequate for electronic device application, indicating slightly smaller energy
      gaps (0.418-0.448 eV) compared to the energy gap of the monolayer (0.536 eV).
      Above all, in light of the band gap engineering, the band gap of the GMO bilayer
      responds to the external electric field sensitively. As a result, a semiconductor
      metal transition occurs at a small critical electric field (EC = 0.22-0.30 V/A).
      It is therefore confirmed that the GMO bilayer is a strong candidate for
      nanoelectronics.

PMID- 27046263
TI  - Does response link updating contribute to the negative compatibility effect?
AB  - Lleras and Enns (2004) argued that the negative compatibility effect (NCE) may
      partly originate from object updating (OU) between a prime and mask. This process
      could occur not only at the feature level, which facilitates target
      identification via feature updating (the updated feature is identical to the
      target in the feature), but also at the response level, which benefits target
      response via response link updating (an updated response link has an identical
      reaction to the target). This study aims to present experimental evidence for the
      latter hypothesis that response link updating is one process that triggers an
      NCE. The design used a 4 (stimuli) to 2 (responses) paradigm in which the left
      hand response was assigned to "1" and "2" and the right-hand response was
      assigned to "3" and "4" (counterbalanced across the participants). Additionally,
      we manipulated the strength of OU (strong, "1" and "3" as primes versus weak OU
      condition, "2" and "4" as primes), response set of prime and target (e.g., same,
      "1" and "3" as both primes and targets versus different response set, "1" and "3"
      as primes or targets but "2" and "4" as targets or primes), and compatibility
      (compatible versus incompatible). The results showed a significant NCE in the
      strong OU (effective object updating) and different response set (separating
      response link updating from OU process) condition. Combined with the response
      time quartiles, which showed a special developmental course for this condition,
      the results suggest that response link updating is one process that triggers an
      NCE when the prime and target come from different response sets, and the
      processing of response link updating does not share identical developmental
      courses as the motor inhibition. 

PMID- 27046264
TI  - How women with high risk pregnancies perceive interactions with healthcare
      professionals when discussing place of birth: A qualitative study.
AB  - OBJECTIVES: to investigate women's perceptions of interactions with obstetricians
      and midwives during high risk pregnancies. The intention was to examine
      differences and similarities between women planning to give birth at home or in
      hospital. DESIGN: qualitative study using semi-structured interviews. Setting
      Maternity department in a hospital in South East England. PARTICIPANTS: twenty
      six women with high risk pregnancies, at least 32 weeks pregnant. Half were
      planning hospital births and half homebirths. MEASUREMENTS AND FINDINGS: semi
      structured interviews to investigate women's perception of communication. Results
      were analysed using thematic analysis. Four themes emerged: women's experiences
      of communication about risks in pregnancy; women's perceptions of professionals'
      beliefs about birth; women's trust in professionals; and women's attitude to
      professionals' advice. Women spoke more positively about communication with
      midwives than with obstetricians. Women planning hospital births expressed trust
      in obstetricians. Women planning homebirths expressed more trust in midwives.
      Women planning hospital births were less likely to question advice from
      professionals. Women planning homebirths were more inclined to trust their own
      instincts when these contradicted professional advice. KEY CONCLUSIONS: women
      prefer to communicate with professionals who are respectful of their thoughts and
      feelings. They may not follow all professional advice. IMPLICATIONS FOR PRACTICE:
      professionals working with women with high risk pregnancies should acknowledge
      women's concerns and deliver impartial, evidence-based advice.

PMID- 27046265
TI  - The closure of rural and remote maternity services: Where are the midwives?
AB  - Decisions to close small maternity units in rural and remote communities have
      often precipitated a community response as women and families rally to save local
      services. But where are the midwives? We argue here that professional bodies such
      as colleges of midwives have a responsibility to advocate more strongly at a
      political level for evidence-based decisionmaking regarding the allocation of
      rural services. We suggest that adopting a comprehensive definition of maternity
      services risk that considers both social and health services risks and their
      impact on clinical risk, could provide a solid basis for effective advocacy by
      professional bodies. 

PMID- 27046266
TI  - One in 4 HIV-Positive South Africans Awaiting ART Initiation Report Condomless
      Sex With a Serodiscordant Partner.

PMID- 27046267
TI  - Impact of Peer Support on Behavior Change Among Newly Diagnosed Australian Gay
      Men.
AB  - INTRODUCTION: Treatment as prevention relies on early uptake of HIV treatment,
      but onward transmission during primary HIV infection may be affected by changes
      in sexual risk behavior after diagnosis. What factors are associated with these
      changes in sexual risk behavior among gay and bisexual men? METHODS: We surveyed
      gay and bisexual men recently diagnosed with HIV about changes to their sexual
      behavior since their diagnosis. In 2008-2010, 263 men described their sexual
      behavior during the 4 weeks before, and during the 4 weeks after, their HIV
      diagnosis. In 2010-2015, 301 men reported how they had changed their sexual
      behavior since their HIV diagnosis. RESULTS: During 2008-2010, 26.6% engaged in
      condomless anal intercourse with non-HIV-positive casual partners during the 4
      weeks before diagnosis, and 9.7% did so during the 4 weeks after diagnosis (P <
      0.001). Only peer support from other people with HIV was associated with this
      change in behavior (OR = 1.42; 95% confidence interval = 1.07 to 1.88; P =
      0.014). Peer support was also associated with partner reduction after diagnosis
      (P = 0.010). During 2010-2015, 31.9% reported that they had increasingly
      disclosed their HIV status to sex partners since their diagnosis, and 74.1%
      reported having reduced the number of men with whom they had sex. Peer support
      was associated with both these changes in behavior (P = 0.003 and P = 0.015,
      respectively). CONCLUSIONS: The risk of onward transmission is likely to be less
      affected by immediate versus early treatment than it is by earlier diagnosis and
      peer support for those newly diagnosed with HIV. Enhanced peer support may
      further reduce the likelihood of onward transmission after diagnosis.

PMID- 27046268
TI  - The Immune System and Neuroinflammation as Potential Sources of Blood-Based
      Biomarkers for Alzheimer's Disease, Parkinson's Disease, and Huntington's
      Disease.
AB  - Neurodegenerative diseases are characterized by a loss of neurons that leads to
      cognitive and behavioral dysfunction. Alzheimer's disease (AD) is the most common
      neurodegenerative disorder affecting millions of people in the United States and
      worldwide, followed by Parkinson's disease (PD). While some early onset forms of
      AD and PD are hereditary, the sporadic or late-onset cases are believed to result
      from lifestyle and environmental factors. On the contrary, Huntington's disease
      (HD) is a neurodegenerative disease solely caused by mutations in the gene for
      huntingtin protein. The disease mechanisms at play for all three disorders remain
      elusive, hampering efforts to develop effective therapeutic interventions. In
      light of this, the discovery of robust biomarkers is crucial in order to identify
      people at risk for AD and PD, preferably before symptoms arise. For all three
      diseases, the identification of biomarkers would not only allow development of
      treatments but also evaluation and adjustment of these with disease progression.
      It is now understood that neuroinflammation plays a crucial role in
      neurodegenerative diseases, along with subsequent immune activation. Therefore,
      research is actively ongoing to discover and evaluate inflammatory and immune
      related biomarkers. Recent progress in this area for AD, PD, and HD is presented
      here.

PMID- 27046269
TI  - Petitioning for Social Change: Letters to Religious Leaders From Gay Men and
      Their Family Allies.
AB  - Coming out is often described as challenging, especially for individuals from
      conservative religious communities (Etengoff, 2013). In an effort to explore how
      these sociocultural conflicts are mediated, gay men (n = 16) and their family
      allies (n = 9) from Christian and Jewish communities wrote letters to religious
      leaders regarding current sexual minority policies and whether they should change
      or remain the same. Petitioning tasks were selected as letters can shift author
      audience relations to allow for non-normative and unscripted expressions (Daiute
      & Lightfoot, 2004). Sixteen of the 25 participants addressed their letters to a
      specific religious figure, illustrating the sociorelational applicability of the
      task. Ninety-three problems and 75 solutions were discussed, supporting prior
      discussions of petitioning tasks as a form of living history and conflict
      mediation (Daiute, 2010). Moreover, 20 of the 25 participants wrote about
      humanization needs (e.g., "We are not freaks at a freak show"), providing new
      conceptual structures for participatory research efforts, policy initiatives, and
      clinical applications.

PMID- 27046270
TI  - A T-RFLP database for the rapid profiling of methanogenic communities in
      anaerobic digesters.
AB  - We present a simple protocol for the cost- and time-efficient profiling of
      methanogens based on T-RFLP fingerprinting of mcrA amplicons. Sequence data were
      compiled from mesophilic lab-scale and full-scale biogas reactors operated under
      various conditions and fed with various substrates. The database facilitates the
      rapid identification of methanogens, thus reducing the need of cloning and
      sequencing. 

PMID- 27046271
TI  - Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the
      JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in
      Guinea.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1001967.]. 

PMID- 27046272
TI  - An approach for estimating item sensitivity to within-person change over time: An
      illustration using the Alzheimer's Disease Assessment Scale-Cognitive subscale
      (ADAS-Cog).
AB  - When assessments are primarily used to measure change over time, it is important
      to evaluate items according to their sensitivity to change, specifically. Items
      that demonstrate good sensitivity to between-person differences at baseline may
      not show good sensitivity to change over time, and vice versa. In this study, we
      applied a longitudinal factor model of change to a widely used cognitive test
      designed to assess global cognitive status in dementia, and contrasted the
      relative sensitivity of items to change. Statistically nested models were
      estimated introducing distinct latent factors related to initial status
      differences between test-takers and within-person latent change across successive
      time points of measurement. Models were estimated using all available
      longitudinal item-level data from the Alzheimer's Disease Assessment Scale
      Cognitive subscale, including participants representing the full-spectrum of
      disease status who were enrolled in the multisite Alzheimer's Disease
      Neuroimaging Initiative. Five of the 13 Alzheimer's Disease Assessment Scale
      Cognitive items demonstrated noticeably higher loadings with respect to
      sensitivity to change. Attending to performance change on only these 5 items
      yielded a clearer picture of cognitive decline more consistent with theoretical
      expectations in comparison to the full 13-item scale. Items that show good
      psychometric properties in cross-sectional studies are not necessarily the best
      items at measuring change over time, such as cognitive decline. Applications of
      the methodological approach described and illustrated in this study can advance
      our understanding regarding the types of items that best detect fine-grained
      early pathological changes in cognition. (PsycINFO Database Record

PMID- 27046273
TI  - Convergent and discriminant validity of alternative measures of maladaptive
      personality traits.
AB  - The purpose of the current study was to test empirically the convergent and
      discriminant validity of 3 recently developed, alternative measures of
      maladaptive personality traits: the Personality Inventory for Diagnostic and
      Statistical Manual for Mental Disorders-Fifth Edition (DSM-5, PID-5; Krueger,
      Derringer, Markon, Watson, & Skodol, 2012), the Computerized Adaptive Test
      Personality Disorder Static Form (CAT-PD-SF; Simms et al., 2011), and Five Factor
      Model Personality Disorder scales (FFMPD; Widiger, Lynam, Miller, & Oltmanns,
      2012). These measures were constructed with different rationales and methods, yet
      the result was highly congruent. The PID-5 and CAT-PD-SF were administered to 286
      community adults with current or a history of mental health treatment; the CAT-PD
      SF and FFMPD scales to 262 such adults; and the PID-5 and FFMPD scales to 266.
      The results indicated good to excellent internal consistency, as well as good to
      excellent convergent and discriminant validity for most scales with a few notable
      exceptions. Suggestions for future research are provided, including the potential
      benefits of scales that are unique to a respective instrument, replication of a
      dependency factor, and exploration as to the basis for instances of questionable
      convergent or discriminant validity. (PsycINFO Database Record

PMID- 27046274
TI  - Interrater reliability of Violence Risk Appraisal Guide scores provided in
      Canadian criminal proceedings.
AB  - Published research suggests that most violence risk assessment tools have
      relatively high levels of interrater reliability, but recent evidence of
      inconsistent scores among forensic examiners in adversarial settings raises
      concerns about the "field reliability" of such measures. This study specifically
      examined the reliability of Violence Risk Appraisal Guide (VRAG) scores in
      Canadian criminal cases identified in the legal database, LexisNexis. Over 250
      reported cases were located that made mention of the VRAG, with 42 of these cases
      containing 2 or more scores that could be submitted to interrater reliability
      analyses. Overall, scores were skewed toward higher risk categories. The
      intraclass correlation (ICCA1) was .66, with pairs of forensic examiners placing
      defendants into the same VRAG risk "bin" in 68% of the cases. For categorical
      risk statements (i.e., low, moderate, high), examiners provided converging
      assessment results in most instances (86%). In terms of potential predictors of
      rater disagreement, there was no evidence for adversarial allegiance in our
      sample. Rater disagreement in the scoring of 1 VRAG item (Psychopathy Checklist
      Revised; Hare, 2003), however, strongly predicted rater disagreement in the
      scoring of the VRAG (r = .58). (PsycINFO Database Record

PMID- 27046275
TI  - Likelihood of obtaining Structured Interview of Reported Symptoms (SIRS) and SIRS
      2 elevations among forensic psychiatric inpatients with screening elevations on
      the Miller Forensic Assessment of Symptoms Test.
AB  - The Miller Forensic Assessment of Symptoms Test (M-FAST) was designed as a
      screening measure for feigned psychiatric symptoms. When M-FAST Total Scores are
      elevated (raw score >=6), the test manual recommends follow-up with a more
      comprehensive measure of feigning, such as the widely used and researched
      Structured Interview of Reported Symptoms (SIRS) or the revised version of the
      test (SIRS-2). The purpose of the current study was to evaluate how often M-FAST
      screening elevations are associated with subsequent elevations on the SIRS or
      SIRS-2. The sample included archival data from 100 forensic psychiatric
      inpatients who obtained M-FAST Total Score elevations >=6 during screening and
      were subsequently administered the SIRS (that was also rescored using SIRS-2
      criteria). Among examinees who elevated the M-FAST over the recommended cutoff,
      66.0% met standard SIRS feigning criteria, 42% met SIRS-2 criteria for feigning,
      and 81.0% obtained at least 1 SIRS/SIRS-2 elevation in the Probable Feigning
      range or higher. These results are consistent with the M-FAST manual guidelines,
      which support the use of the >=6 M-FAST cutoff score to screen for potential
      feigning (but not as an independent marker of feigning). A higher M-FAST cutoff
      score of >=16 was associated with subsequently meeting full SIRS criteria for
      feigning in 100.0% of protocols. Because the SIRS criteria were designed to have
      very low false positive rates, these findings indicate that more confident
      assertions about feigning can be made when elevations reach this level on the
      MFAST. (PsycINFO Database Record

PMID- 27046276
TI  - Validation of the Narcissistic Grandiosity Scale and creation of reduced item
      variants.
AB  - The Narcissistic Grandiosity Scale (NGS) is a short adjective-based measure of
      narcissistic grandiosity (Rosenthal, Hooley, & Steshenko, 2007). The NGS has
      already shown promise as a measure of grandiose narcissism, but it has never been
      the subject of a formal validation study. In the current study (N = 870 across 3
      samples), the factor structure of NGS was examined and item response theory
      analyses were used to generate abbreviated versions of the scale. The NGS scales'
      relations to measures of grandiose and vulnerable narcissism, the five-factor
      model (FFM), the interpersonal circumplex, self-esteem, and the Personality
      Inventory of the Diagnostic and Statistical Manual for Mental Disorders-Fifth
      Edition (DSM-5, PID-5) were assessed. The correlation profile of the NGS was also
      correlated with expert ratings of prototypical cases of narcissistic personality
      disorder using both the FFM and PID-5 trait profiles. Overall, the NGS was found
      to be a unidimensional measure of narcissistic grandiosity with good convergent,
      discriminant, and criterion validity. The abbreviated versions of the NGS
      manifested strong reliability and associations entirely consistent with the full
      version. (PsycINFO Database Record

PMID- 27046277
TI  - Multifacet assessment of capability for suicide: Development and prospective
      validation of the Acquired Capability With Rehearsal for Suicide Scale.
AB  - The interpersonal theory of suicide proposes that acquired capability facilitates
      transformation of suicidal desire into lethal self-destructive behavior (Joiner,
      2005). A new measure, the Acquired Capability With Rehearsal for Suicide Scale
      (ACWRSS), was devised to capture the key facets of acquired capability-pain
      tolerance and fearlessness of death-while also incorporating deliberate and
      active means to increase preparedness for suicide. The factor structure of the
      ACWRSS was tested using confirmatory factor analysis (n = 611). The 7-item ACWRSS
      conformed to the hypothesized 3-factor structure, demonstrating excellent fit and
      good internal consistency (alpha = .83). Measurement invariance across gender was
      also demonstrated on configural, metric, and scalar levels. Next, in the first
      longitudinal study of the association between acquired capability and suicide
      ideation, intention, and readiness (n = 234), the acquired capability facets
      prospectively predicted specific phases in the motivational-volitional pathway
      toward suicide readiness. Moreover, 2 of the acquired capability components
      mediated the relationship between baseline nonsuicidal self-injury and suicide
      readiness at follow-up. In an inpatient psychiatric sample (n = 108), the ACWRSS
      was significantly correlated with prior suicide attempts and thoughts and
      episodes of nonsuicidal self-injury, and its facets demonstrated differential
      sensitivity to change. The ACWRSS is the first measure of acquired capability
      that reliably and validly captures all key facets of this critical component of
      the interpersonal theory of suicide. Its brevity enhances its utility for both
      research and clinical settings. (PsycINFO Database Record

PMID- 27046278
TI  - Factor structure of the Differential Ability Scales-Second Edition: Exploratory
      and hierarchical factor analyses with the core subtests.
AB  - The present study examined the factor structure of the Differential Ability
      Scales-Second Edition (DAS-II; Elliott, 2007a) standardization sample using
      exploratory factor analyses, multiple factor extraction criteria, and
      hierarchical exploratory factor analyses (Schmid & Leiman, 1957) not included in
      the DAS-II Introductory and Technical Handbook (Elliott, 2007b). Exploratory
      factor analyses with multiple factor extraction criteria and hierarchical
      analyses with the Schmid and Leiman (1957) procedure were conducted with the 3
      DAS-II standardization samples (Lower Early Years [Ages 2:6-3:5], Upper Early
      Years [Ages 3:6-6:11], School-Age [Ages 7:0-17:11]). All factor extraction
      criteria suggested 1 factor despite the author and publisher recommended and
      promoted 2 (Ages 2:6-3:5) or 3 (Ages 3:6-6:11, Ages 7:0-17:11) factors. Results
      indicated that most DAS-II subtests were properly associated with the
      theoretically proposed first-order factors. Hierarchical exploratory analyses
      with the Schmid and Leiman procedure, however, found that the hierarchical g
      factor accounted for large portions of total and common variance, while the 2 or
      3 first-order factors accounted for small portions of total and common variance.
      It was concluded that the DAS-II provides strong measurement of general
      intelligence but clinical interpretation should be primarily at that level.
      (PsycINFO Database Record

PMID- 27046279
TI  - Realization of Minimum and Maximum Gate Function in Ta2O5-based Memristive
      Devices.
AB  - Redox-based resistive switching devices (ReRAM) are considered key enablers for
      future non-volatile memory and logic applications. Functionally enhanced ReRAM
      devices could enable new hardware concepts, e.g. logic-in-memory or neuromorphic
      applications. In this work, we demonstrate the implementation of ReRAM-based
      fuzzy logic gates using Ta2O5 devices to enable analogous Minimum and Maximum
      operations. The realized gates consist of two anti-serially connected ReRAM cells
      offering two inputs and one output. The cells offer an endurance up to 10(6)
      cycles. By means of exemplary input signals, each gate functionality is verified
      and signal constraints are highlighted. This realization could improve the
      efficiency of analogous processing tasks such as sorting networks in the future. 

PMID- 27046280
TI  - The Proportion of Signet Ring Cell Component in Patients with Localized Gastric
      Adenocarcinoma Correlates with the Degree of Response to Pre-Operative
      Chemoradiation.
AB  - BACKGROUND: Patients with localized gastric adenocarcinoma (LGAC), who get pre
      operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical
      variables/biomarkers are not established. METHODS: We analyzed 107 LGAC patients
      who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence
      of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was
      assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete
      response (pathCR) or <pathCR in the resected specimens. RESULTS: Most patients
      were men (60%), had stage cIII LGAC (50%), and received chemotherapy before
      chemoradiation (93%). Most had G3 tumors (78%) and SRC (58%). Presence of SRC was
      associated with a lower rate of pathCR (11 vs. 36%, p = 0.004), and the
      association remained significant even with a low percentage of SRC (1-10%; p =
      0.014). The higher the fraction of SRC, the lower was the probability of pathCR
      (p = 0.03). G3 and SRC led to a shorter overall survival (OS) (p = 0.046 and p =
      0.038, respectively). yp stage independently prognosticated OS and recurrence
      free survival (p < 0.001). CONCLUSION: Our novel findings suggest that LGACs with
      SRC are relatively chemoradiation resistant compared to LGACs without SRC. A
      higher fraction of SRC is associated with higher resistance. Upon
      validation/biomarker(s) evaluation, reporting of the fraction of SRC may be
      warranted.

PMID- 27046281
TI  - Helical Folding-Induced Stabilization of Ferromagnetic Polyradicals Based on
      Triarylmethyl Radical Derivatives.
AB  - Magnetic ordering in purely organic pi-conjugated materials is a challenging,
      rare, and desirable event. The interest lies on the unique magnetic properties
      derived from high-spin carbon-based polymers/macromolecules tailored through
      appropriate synthetic routes. Ground-breaking achievements have been reported
      regarding magnetic ordering in an organic polymer using spin clusters as building
      blocks. This strategy leads to two-dimensional extended polyradicals with a
      concomitant loss of appealing macroscopic properties such as expected magnetic
      anisotropy in elongated shaped macromolecules containing carbon-bearing radicals.
      Here we provide compelling evidence of a secondary structure-induced
      stabilization of ferromagnetic polyradicals with robust magnetic properties and
      strongly suggest revisiting a discarded attempt to obtain polymeric linear-like
      radicals. An alternative synthetic approach is also proposed, based on
      polyradicals obtained from discrete molecular precursors (oligomers) long enough
      to ensure a secondary structure, rather than from polymerization processes.

PMID- 27046285
TI  - Trial use of a polymethylmethacrylate membrane for the removal of free
      immunoglobulin light chains in dialysis patients.
AB  - Background. Free immunoglobulin light chains (FLCs) accumulate at high levels in
      the blood of dialysis patients and are likely to cause immunodeficiency during
      periods of dialysis. Our group examined the blood FLC concentration, kappa/lambda
      ratio and rates of FLC removal in different dialysis modes using different
      dialysis membranes. Methods. Polymethylmethacrylate (PMMA) membrane (BG-PQ,
      Toray) under the haemodialysis (HD) condition was used for seven chronic
      maintenance dialysis patients who had been treated by hemodiafiltration (HDF)
      (five polyester-polymer alloy (PEPA) and two polysulphone) in a crossover
      fashion. FLCs in serum were measured with a FREELITETM Human Kappa Free Kit and
      Lambda Free Kit prepared by Binding Site, UK (supplied by Medical & Biological
      Laboratories Co., Ltd, Japan). Each kappa-type and lambda-type FLC was
      quantitatively measured with a Dade Behring BNIITM. Western blotting was
      conducted using a goat anti-human kappaFLC polyclonal antibody. Results. The
      kappa and lambda serum FLCs in HD patients (n = 7) were 157.4 +/- 88.9 and 121.9
      +/- 56.3 mg/L, respectively, and were accumulated in concentrations 4- to 16-fold
      higher than the concentrations in healthy controls. The kappa/lambda ratio was
      included in the reference range (0.26-1.65). In the HD cases dialysed with PMMA
      membrane, the FLCs were removed mainly by adsorption, leaving only very small
      quantities in the whole dialysis waste fluid. The ratio between the total removed
      quantity and albumin leakage ((kappa+lambda)/Alb) was higher in the PMMA HD group
      than in the HDF group, and the rate of kappaFLC removal was higher than the rate
      of lambdaFLC removal. The serum kappaFLC in dialysis patients had a multimer
      structure. In western blotting, the adsorbed kappaFLC (including multimer
      structure) detected in the PMMA membrane exceeded that detected in the dialysate
      with the polysulphone membrane. Conclusions. Although the FLCs were removed at
      high rates under the HDF condition, they were also effectively removed by
      adsorption with the PMMA membrane under the HD condition. It may be possible to
      effectively remove the FLC multimer with a PMMA membrane via adsorption. In
      future studies on FLC removal in patients with chronic renal failure, it will be
      necessary to assess not only the quantity of simple removal from the blood but
      also the qualitative properties, such as the degree to which accumulation and
      removal rates depend on the kappa/lambda ratio and multimer structures.

PMID- 27046286
TI  - CAEP 2015 Academic Symposium: Recommendations for University Governance and
      Administration for Emergency Medicine.
AB  - OBJECTIVE: 1) To identify the strengths and challenges of governance structures
      in academic emergency medicine (EM), and 2) to make recommendations on principles
      and approaches that may guide improvements. METHODS: Over the course of 9 months,
      eight established EM leaders met by teleconference, reviewed the literature, and
      discussed their findings and experiences to arrive at recommendations on
      governance in academic units of EM. The results and recommendations were
      presented at the annual Canadian Association of Emergency Physicians (CAEP)
      Academic Symposium, where attendees provided feedback. The updated
      recommendations were subsequently distributed to the CAEP Academic Section for
      further input, and the final recommendations were decided by consensus. RESULTS:
      The panel identified four governance areas of interest: 1) the elements of
      governance; 2) the relationships between emergency physicians and academic units
      of EM, and between the academic units of EM and faculty of medicine; 3) current
      status of governance in Canadian academic units of EM; and 4) essential elements
      of good governance. Six recommendations were developed around three themes,
      including 1) the importance of good governance; 2) the purposes of an academic
      unit of EM; and 3) essential elements for better governance for academic units of
      EM. Recommendations included identifying the importance of good governance,
      recognizing the need to adapt to the different models depending on the local
      environment; seeking full departmental status, provided it is mutually beneficial
      to EM and the faculty of medicine (and health authority); using a consultation
      service to learn from the experience of other academic units of EM; and
      establishing an annual forum for EM leaders. CONCLUSION: Although governance of
      academic EM is complex, there are ways to iteratively improve the mission of
      academic units of EM: providing exceptional patient care through research and
      education. Although there is no one-size-fits-all guide, there are practical
      recommended steps for academic units of EM to consider.

PMID- 27046287
TI  - Reaction Dynamics of O((3)P) + Propyne: I. Primary Products, Branching Ratios,
      and Role of Intersystem Crossing from Crossed Molecular Beam Experiments.
AB  - We performed synergic experimental/theoretical studies on the mechanism of the
      O((3)P) + propyne reaction by combining crossed molecular beams experiments with
      mass-spectrometric detection and time-of-flight analysis at 9.2 kcal/mol
      collision energy (Ec) with ab initio electronic structure calculations at a high
      level of theory of the relevant triplet and singlet potential energy surfaces
      (PESs) and statistical calculations of branching ratios (BRs) taking into account
      intersystem crossing (ISC). In this paper (I) we report the results of the
      experimental investigation, while the accompanying paper (II) shows results of
      the theoretical investigation with comparison to experimental results. By
      exploiting soft electron ionization detection to suppress/mitigate the effects of
      the dissociative ionization of reactants, products, and background gases, product
      angular and velocity distributions at different charge-to-mass ratios were
      measured. From the laboratory data angular and translational energy distributions
      in the center-of-mass system were obtained for the five competing most important
      product channels, and product BRs were derived. The reactive interaction of
      O((3)P) with propyne under single collision conditions is mainly leading to the
      rupture of the three-carbon atom chain, with production of the radical products
      methylketenyl + atomic hydrogen (BR = 0.04), methyl + ketenyl (BR = 0.10), and
      vinyl + formyl (BR = 0.11) and the molecular products ethylidene/ethylene +
      carbon monoxide (BR = 0.74) and propandienal + molecular hydrogen (BR = 0.01).
      Because some of the products can only be formed via ISC from the entrance triplet
      to the low-lying singlet PES, we infer from their BRs an amount of ISC larger
      than 80%. This value is dramatically large when compared to the negligible ISC
      reported for the O((3)P) reaction with the simplest alkyne, acetylene. At the
      same time, it is much larger than that (~20%) recently observed in the related
      reaction of the three-carbon atom alkene, O((3)P) + propene at a comparable Ec.
      This poses the question of how important it is to consider nonadiabatic effects
      and their dependence on molecular structure for this kind of combustion
      reactions. The prevalence of the CH3 over the H displacement channels is not
      explained by invoking a preference for the addition on the methyl-substituted
      acetylenic carbon atom, but rather it is believed to be due to the different
      tendencies of the two addition triplet intermediates CH3CCHO (preferentially
      leading to H elimination) and CH3COCH (preferentially leading to CH3 elimination)
      to undergo ISC to the underlying singlet PES. It is concluded that the main
      coproduct of the CO forming channel is singlet ethylidene ((1)CH3CH) rather than
      ground-state ethylene. By comparing the derived BRs with those very recently
      derived from kinetics studies at room temperature and 4 Torr we obtained
      information on how BRs vary with collision energy. The extent of ISC is estimated
      to remain essentially constant (~85%) with increasing Ec from ~1 to ~10 kcal/mol.
      The present experimental results shed light on the mechanism of the title
      reaction at energies comparable to those involved in combustion and, when
      compared with the results from the statistical calculations on the ab initio
      coupled PESs (see accompanying paper II), lead to an in-depth understanding of
      the rather complex reaction mechanism of O + propyne. The overall results are
      expected to contribute to the development of more refined models of hydrocarbon
      combustion. 

PMID- 27046288
TI  - Sexual communication in day-flying Lepidoptera with special reference to
      castniids or 'butterfly-moths'.
AB  - Butterflies and moths are subject to different evolutionary pressures that affect
      several aspects of their behaviour and physiology, particularly sexual
      communication. Butterflies are day-flying insects (excluding hedylids) whose
      partner-finding strategy is mainly based on visual cues and female butterflies
      having apparently lost the typical sex pheromone glands. Moths, in contrast, are
      mostly night-flyers and use female-released long-range pheromones for partner
      finding. However, some moth families are exclusively day-flyers, and therefore
      subject to evolutionary pressures similar to those endured by butterflies. Among
      them, the Castniidae, also called 'butterfly-moths' or 'sun-moths', behave like
      butterflies and, thus, castniid females appear to have also lost their pheromone
      glands, an unparallel attribute in the world of moths. In this paper, we review
      the sexual communication strategy in day-flying Lepidoptera, mainly butterflies
      (superfamily Papilionoidea), Zygaenidae and Castniidae moths, and compare their
      mating behaviour with that of moth families of nocturnal habits, paying
      particular attention to the recently discovered butterfly-like partner-finding
      strategy of castniids and the fascinating facts and debates that led to its
      discovery.

PMID- 27046289
TI  - Spontaneous Unzipping of Xylonucleic Acid Assisted by a Single-Walled Carbon
      Nanotube: A Computational Study.
AB  - Xenonucleic acids are synthetic nucleic acid analogues that are potential
      candidates for antisense or antigene therapy owing to their higher thermal and
      enzymatic stability compared to that of naturally occurring ones at physiological
      conditions. We investigate the binding and unzipping of xylonucleic acid (XNA)
      containing xylose (a stereoisomer of ribose) sugar in its backbone assisted by a
      single walled carbon nanotube (SWCNT) using extensive atomistic molecular
      dynamics simulations. Our simulations confirm XNA to undergo faster unzipping
      compared to a double stranded RNA with the same nucleobase sequence which is
      presumably due to the near orthogonal base pairing arrangement of the constituent
      nucleobases of XNA at physiologically relevant conditions (in terms of
      temperature and salt concentration). The interaction between XNA and SWCNT mimics
      that of a small interfering RNA (siRNA) and RNA-induced silencing complex (RISC)
      during a typical RNA induced gene silencing process where the duplex chain
      unwinding of the siRNA is of primordial importance. Our study may find relevance
      in designing a more efficient and safer delivery platform for xenonucleic acids
      by grafting these RNA analogues to SWCNT into an infected target cell. This
      unveils promising applications of XNA in the field of gene delivery for antisense
      therapies.

PMID- 27046290
TI  - A multi-national report on stereotactic body radiotherapy for oligometastases:
      Patient selection and follow-up.
AB  - Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly
      used with few evidenced-based guidelines. We conducted a survey to determine
      patient selection and follow-up practice patterns. Materials and methods Seven
      institutions from US, Canada, Europe, and Australia that recommend SBRT for
      oligometastases participated in a 72-item survey. Levels of agreement were
      categorized as strong (6-7 common responses), moderate (4-5), low (2-3), or no
      agreement. Results There was strong agreement for recommending SBRT for
      eradication of all detectable oligometastases with most members limiting the
      number of metastases to five (range 2-5) and three within a single organ (range 2
      5). There was moderate agreement for recommending SBRT as consolidative therapy
      after systemic therapy. There was strong agreement for requiring adequate
      performance status and no concurrent chemotherapy. Additional areas of strong
      agreement included staging evaluations, primary diagnosis, target sites, and
      follow-up recommendations. Several differences emerged, including the use of SBRT
      for sarcoma oligometastases, treatment response evaluation, and which imaging
      should be performed during follow-up. Conclusion Significant commonalities and
      variations exist for patient selection and follow-up recommendations for SBRT for
      oligometastases. Information from this survey may serve to help clarify the
      current landscape. 

PMID- 27046291
TI  - Implementation of a care bundle and evaluation of risk factors for surgical site
      infection in cranial neurosurgery.
AB  - OBJECTIVES: Surgical site infection [SSI] increases mortality, morbidity and
      length of hospital stay. Peri-operative 'care bundles' have reduced SSI in some
      fields of surgery. The aim of this study was to determine the impact of bundle
      compliance on SSI in patients undergoing a craniotomy. PATIENTS AND METHOD:
      Cohort study of patients [N=1253] undergoing a craniotomy over 17 months at a
      single centre. SSI was defined as arising within 30days of operation or 1year
      where an implant(s) remains. 'Bundle compliance' required administration of
      antibiotics <60min of induction, maintenance of intraoperative blood sugar (BM)
      <11mmol and temperature at >36 degrees C. SSI incidence was compared between
      bundle compliant and non-compliant groups. Case mix adjustment was performed
      using binary logistic regression. RESULTS: Over the study period, 1253 procedures
      were carried out and 66 patients (5.3%) developed a SSI. The majority (38, 57.6%)
      of these cultured Staphyloccoccus species. Only the use of an implant was found
      to be an independent risk factor for SSI [AOR 2.5, p<0.005, 95%CI 1.4, 4.3]. The
      use of the bundle did not reduce the occurrence of SSI. CONCLUSIONS: An evidence
      based bundle did not reduce SSI in this neurosurgical series. The use of an
      implant was an independent risk factor of its occurrence.

PMID- 27046292
TI  - Recurrent optic neuritis and neuromyelitis optica-IgG following first and second
      human papillomavirus vaccinations.
AB  - Human papillomavirus (HPV) vaccine is widely used to prevent cervical cancer
      caused by certain types of HPV in girls and young women. Demyelinating disorders
      within months following HPV innoculation have been reported, but the causal link
      between HPV vaccination and the onset of demyelinating disorders have not been
      certain. We report a case of neuromyelitis optica spectrum disorder (NMOSD) that
      was noteworthy because optic neuritis (ON) occurred in a very close temporal
      association with both the first and second HPV vaccinations, which might suggest
      an association between HPV vaccination and the development of NMO-IgG and
      recurrent ON. This emphasizes the necessity for continuing surveillance for
      adverse events after HPV vaccination. 

PMID- 27046293
TI  - Medium Vacuum Electron Emitter as Soft Atmospheric Pressure Chemical Ionization
      Source for Organic Molecules.
AB  - An electron emitter as a soft atmospheric pressure chemical ionization source is
      presented, which operates at inner pressures of the device in the medium vacuum
      range (>10(-3) hPa). Conventional nonradioactive electron emitters require high
      vacuum (<10(-6) hPa) to prevent electrical sparkovers. The emitter presented here
      contains structural modifications of an existing setup, which inhibits electrical
      breakdowns up to 10(-2) hPa at 8 kV acceleration voltage. The increased inner
      pressure reduces the ionization efficiency until 10(-3) hPa-achievable without a
      turbomolecular pump-by 2% compared to high-vacuum conditions. This can be
      compensated with an increase of the electron source output. The functionality of
      this ion source is demonstrated with mass spectrometric and ion mobility
      measurements of acetone, eucalyptol, and diisopropyl methanephosphonate.
      Additional mass spectrometric measurements of 20 different organic compounds
      demonstrate the soft characteristics of this ionization source.

PMID- 27046295
TI  - Poly(lactic acid)-Mass production, processing, industrial applications, and end
      of life.
AB  - Global awareness of material sustainability has increased the demand for bio
      based polymers like poly(lactic acid) (PLA), which are seen as a desirable
      alternative to fossil-based polymers because they have less environmental impact.
      PLA is an aliphatic polyester, primarily produced by industrial polycondensation
      of lactic acid and/or ring-opening polymerization of lactide. Melt processing is
      the main technique used for mass production of PLA products for the medical,
      textile, plasticulture, and packaging industries. To fulfill additional desirable
      product properties and extend product use, PLA has been blended with other resins
      or compounded with different fillers such as fibers, and micro- and
      nanoparticles. This paper presents a review of the current status of PLA mass
      production, processing techniques and current applications, and also covers the
      methods to tailor PLA properties, the main PLA degradation reactions, PLA
      products' end-of-life scenarios and the environmental footprint of this unique
      polymer.

PMID- 27046294
TI  - Assays for Qualification and Quality Stratification of Clinical Biospecimens Used
      in Research: A Technical Report from the ISBER Biospecimen Science Working Group.
AB  - This technical report presents quality control (QC) assays that can be performed
      in order to qualify clinical biospecimens that have been biobanked for use in
      research. Some QC assays are specific to a disease area. Some QC assays are
      specific to a particular downstream analytical platform. When such a
      qualification is not possible, QC assays are presented that can be performed to
      stratify clinical biospecimens according to their biomolecular quality.

PMID- 27046296
TI  - Mirror therapy in children with hemiparesis: a randomized observer-blinded trial.
AB  - AIM: To determine the efficacy of mirror therapy in children with hemiparesis.
      METHOD: The design was an observer-blinded parallel-group randomized controlled
      trial (International Standard Randomised Controlled Trial Number 48748291).
      Randomization was computer-generated, 1:1 allocation to mirror therapy or
      comparison groups. The settings were home-based intervention and tertiary centre
      assessments. Participants were 90 children with hemiparesis aged 7 to 17 years.
      Intervention was 15 minutes per day of simultaneous arm training, 5 days a week,
      for 5 weeks. The mirror therapy group used a mirror; those in the comparison
      group looked at their paretic limb. Assessments comprised measures of upper limb
      strength, function (Melbourne Assessment 2), daily performance (ABILHAND-Kids),
      and sensory function at weeks 0 (T0 ), 5 (T1 ), and 10 (T2 ). RESULTS: There were
      no significant differences in outcomes and their progression over time between
      the mirror therapy and comparison groups. Post-hoc intention-to-treat analyses
      showed significant improvements in both groups for grasp strength (T0 -T1
      +12.6%), pinch strength (T0 -T2 +9.1%), upper limb function in terms of accuracy
      (T0 -T2 +2.7%) and fluency (T0 -T2 +5.0%), as well as daily performance (T0 -T2
      +16.6%). Per protocol analyses showed additional improvements in dexterity (T0 
      T2 +4.0%). INTERPRETATION: The use of the mirror illusion during therapy had no
      significant effect on treatment outcomes. However, 5 weeks of daily simultaneous
      arm training significantly improved paretic upper limb strength, function, and
      daily use.

PMID- 27046297
TI  - What Matters for Calculating Insulin Bolus Dose?

PMID- 27046298
TI  - Diffractive imaging of a rotational wavepacket in nitrogen molecules with
      femtosecond megaelectronvolt electron pulses.
AB  - Imaging changes in molecular geometries on their natural femtosecond timescale
      with sub-Angstrom spatial precision is one of the critical challenges in the
      chemical sciences, as the nuclear geometry changes determine the molecular
      reactivity. For photoexcited molecules, the nuclear dynamics determine the
      photoenergy conversion path and efficiency. Here we report a gas-phase electron
      diffraction experiment using megaelectronvolt (MeV) electrons, where we captured
      the rotational wavepacket dynamics of nonadiabatically laser-aligned nitrogen
      molecules. We achieved a combination of 100 fs root-mean-squared temporal
      resolution and sub-Angstrom (0.76 A) spatial resolution that makes it possible to
      resolve the position of the nuclei within the molecule. In addition, the
      diffraction patterns reveal the angular distribution of the molecules, which
      changes from prolate (aligned) to oblate (anti-aligned) in 300 fs. Our results
      demonstrate a significant and promising step towards making atomically resolved
      movies of molecular reactions. 

PMID- 27046299
TI  - Comparing Unmet Needs to Optimize Quality: Characterizing Inpatient and
      Outpatient Palliative Care Populations.
AB  - CONTEXT: Palliative care (PC) consultation services are available in most
      hospitals; outpatient services are rapidly growing to meet the needs of patients
      at earlier stages of the disease trajectory. OBJECTIVES: We aimed to compare the
      unmet needs of PC patients by location of care to better characterize these
      populations. METHODS: This cross-sectional secondary analysis examined patients
      receiving hospital and outpatient-based PC across 10 community and academic
      organizations in the Global Palliative Care Quality Alliance. We identified unmet
      symptom, advance care planning, and functional needs within our database from
      October 23, 2012 to January 22, 2015. Kruskal-Wallis, chi-square, and Fisher
      exact tests were performed. RESULTS: We evaluated 633 unique patients. Inpatients
      (n = 216) were older than outpatients (n = 417; 73 vs. 64 years, P < 0.0001).
      Seventy-six inpatients (38%) had a Palliative Performance Scale score <=30%; no
      outpatients did (P < 0.0001). More inpatients rated their quality of life as poor
      compared with outpatients (39% vs. 21%, P = 0.0001). We found that outpatients
      presented with more unresolved pain than inpatients (58.5% vs. 4.1%, P < 0.0001).
      Conversely, more inpatients presented with unresolved anorexia (52.3% vs. 35.8%,
      P = 0.002) and dysphagia (28.1% vs. 5.4%, P < 0.0001) than outpatients. We found
      that inpatient setting was independently associated with lower performance status
      (odds ratio = 0.068, 95% confidence interval = 0.038-0.120, P < 0.0001).
      CONCLUSION: Compared with inpatients, outpatients are more burdened by pain at
      first PC encounter yet experience higher quality of life and better performance
      status. These findings suggest different clinician skillsets, and assessments are
      needed depending on the setting of PC consultation.

PMID- 27046300
TI  - Hearing Loss in Hospice and Palliative Care: A National Survey of Providers.
AB  - CONTEXT: Age-related hearing loss can impair patient-provider communication about
      symptom management, goals of care, and end-of-life decision-making. OBJECTIVES:
      To determine whether hospice and palliative care providers screen for or received
      training about hearing loss, believe it impacts patient care, and use strategies
      to optimize communication. METHODS: This was a national survey of hospice and
      palliative care providers conducted via email and social media. Survey questions
      were pilot tested with multidisciplinary providers in San Francisco. RESULTS: Of
      510 responses (55% age 50+ years, 65% female, 64% in practice 5+ years, 57%
      practiced hospital-based palliative care, 45% hospice), 315 were physicians, 50
      nurses, 48 nurse practitioners, 58 social workers, and 39 chaplains. Ninety-one
      percent reported that hearing loss has some or great impact on the quality of
      care for older adults. Eighty-eight percent recalled a situation where hearing
      loss created a communication problem with a patient and 56% a communication
      problem with a caregiver. Eighty-seven percent of physicians, nurses, and nurse
      practitioners reported not screening for hearing loss. Although 61% felt
      comfortable with their communication skills for patients with hearing loss, only
      21% reported having received formal training in its management, 31% were
      unfamiliar with resources for patients with hearing loss, and 38% had never heard
      of a pocket talker amplification device. CONCLUSION: Hospice and palliative
      medicine providers believe age-related hearing loss impacts care yet most do not
      screen. Although they feel they are managing well, few have formal training.
      Knowledge about management approaches and resources is suboptimal.

PMID- 27046301
TI  - Factors associated with body image dissatisfaction and distortion among Iranian
      women.
AB  - The prevalence of body image dissatisfaction is considered high in both developed
      and developing countries. It has been shown that many factors affect the body
      image dissatisfaction. However, because of the economical and cultural
      differences, it seems that these affecting factors should be determined in each
      region. So, the present study was designed to evaluate the prevalence and
      associated factors with body image dissatisfaction and distortion among Iranian
      women. Body image perception was analyzed in 500 women through the Stunkard
      figure rating system. The International Physical Activity Questionnaire was used
      for assessing physical activity level. The information about age, marital status
      and socioeconomic status was recorded by general questionnaire. The one-way ANOVA
      and regression were used for statistical analysis. By increasing the BMI
      categories from underweight to obesity, participants tended to perceive their
      body size thinner than real body size. The regression models indicated that the
      body image distortion was significantly increased with increasing the BMI
      (p=0.002) and physical activity level (p=0.008). Besides, dissatisfaction by
      being heavier than ideal was significantly associated with higher BMI (OR (95%
      CI). 1.21 (1.03, 1.17)). Considering the high prevalence of body image
      dissatisfaction among Iranian women, for preventing psychological problems and
      eating disorders, appropriate public health programs for increasing awareness
      about healthy body size were needed.

PMID- 27046302
TI  - Weight and weight change and risk of acute myocardial infarction and heart
      failure - the HUNT Study.
AB  - OBJECTIVES: To delineate the association of weight with cardiovascular health
      throughout adulthood. METHODS: We conducted a population-based prospective cohort
      study of 26 097 community-dwelling individuals who were followed for 11.4 years
      with measurements of cardiovascular risk factors and common chronic disorders.
      Body weight and height were directly measured at baseline in 1995-1997 as they
      had been 10 and 30 years prior to baseline. From these measurements, we estimated
      average body mass index (BMI) over time and calculated weight change. RESULTS:
      The association of average BMI with acute myocardial infarction (AMI) became
      weaker with adjustment for the most recent BMI measurement, whilst this
      adjustment had a more limited effect on associations with heart failure (HF)
      risk. For example, the multi-adjusted hazard ratios for AMI in a comparison of
      individuals with average BMI until baseline >=35 kg m(-2) and between 18.5 and
      22.4 kg m(-2) decreased from 1.75 [95% confidence interval (CI) 1.04-2.95] to
      1.32 (0.73-2.40). The corresponding numbers for HF were 3.12 (1.85-5.27) and 2.95
      (1.53-5.71), respectively. The associations between weight change and risk of AMI
      and HF were U-shaped, with stable weight showing the lowest risk. CONCLUSION:
      Sustained overweight or obesity over time is associated with increased risk of
      HF, even after adjustment for the most recent BMI. For AMI risk, the most recent
      BMI appears to be the most important. Weight change also increases risks for both
      outcomes beyond the effects of BMI. Our results suggest that a global epidemic of
      obesity is likely to increase the incidence of HF, even if BMI in middle age can
      be controlled.

PMID- 27046303
TI  - Does the American College of Surgeons National Surgical Quality Improvement
      Program pediatric provide actionable quality improvement data for surgical
      neonates?
AB  - BACKGROUND/PURPOSE: The purpose of this project was to examine the American
      College of Surgeons National Surgical Quality Improvement Program Pediatric
      (ACSNSQIP-P) Participant Use File (PUF) to compare risk-adjusted outcomes of
      neonates versus other pediatric surgical patients. METHODS: In the ACS-NSQIP-P
      2012-2013 PUF, patients were classified as preterm neonate, term neonate, or
      nonneonate at the time of surgery. The primary outcomes were 30-day mortality and
      composite morbidity. Patient characteristics significantly associated with the
      primary outcomes were used to build a multivariate logistic regression model.
      RESULTS: The overall 30-day mortality rate for preterm neonates, term neonate,
      and nonneonates was 4.9%, 2.0%, 0.1%, respectively (p<0.0001). The overall 30-day
      morbidity rate for preterm neonates, term neonates, and nonneonates was 27.0%,
      17.4%, 6.4%, respectively (p<0.0001). After adjustment for preoperative and
      operative risk factors, both preterm (adjusted odds ratio, 95% CI: 2.0, 1.4-3.0)
      and term neonates (aOR, 95% CI: 1.9, 1.2-3.1) had a significantly increased odds
      of 30-day mortality compared to nonneonates. CONCLUSION: Surgical neonates are a
      cohort who are particularity susceptible to postoperative morbidity and mortality
      after adjusting for preoperative and operative risk factors. Collaborative
      efforts focusing on surgical neonates are needed to understand the unique
      characteristics of this cohort and identify the areas where the morbidity and
      mortality can be improved.

PMID- 27046304
TI  - Combined low miR-34s are associated with unfavorable prognosis in children with
      hepatoblastoma: A Chinese population-based study.
AB  - PURPOSE: The aim of this study is to identify the association between miR-34's
      family and the prognosis of HB in a large Asian cohort and to explore the
      interaction of miR-34 with other independent risk factors in the process of
      affecting prognosis of HB. METHODS: We retrospectively reviewed 78 children with
      HB (36 female, 42 male) managed in our institutions between 2007 and 2014. The
      expression of miR-34 was detected by real-time PCR. Prognostic factors were
      evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS:
      For the entire cohort of 76 patients, The normalized real-time PCR results showed
      that all three miRNAs were deregulated in tumor tissues as compared with
      corresponding noncancerous tissue samples. Descriptive survival statistics and
      Kaplan-Meier curves suggested that AFP levels, metastases, vascular invasion,
      PRETEXT stage and miR-34 had prognostic significance in this relatively selected
      cohort. After that we made miR-34 into different combinations. The results
      demonstrated that combined low miR-34a and miR-34b (HR:2.212, P=0.016), combined
      low miR-34a and miR-34c (HR:1.984, P=0.025) and combined low miR-34a, miR-34b and
      miR-34c (HR:3.569, P=0.001) were independent prognostic factors of HB. We further
      conduct stratified analysis of the impact of other identified risk factors on the
      combined low of three miR-34. CONCLUSIONS: In this study, we found that miR-34s
      were deregulated in tumor tissues compared with corresponding noncancerous tissue
      samples. We also confirmed that combined low miR-34 is an independent prognostic
      factor related with HB.

PMID- 27046305
TI  - Palladium(0) Nanoparticle Formation, Stabilization, and Mechanistic Studies:
      Pd(acac)2 as a Preferred Precursor, [Bu4N]2HPO4 Stabilizer, plus the
      Stoichiometry, Kinetics, and Minimal, Four-Step Mechanism of the Palladium
      Nanoparticle Formation and Subsequent Agglomeration Reactions.
AB  - Palladium(0) nanoparticles continue to be important in the field of catalysis.
      However, and despite the many prior reports of Pd(0)n nanoparticles, missing is a
      study that reports the kinetically controlled formation of Pd(0)n nanoparticles
      with the simple stabilizer [Bu4N]2HPO4 in an established, balanced formation
      reaction where the kinetics and mechanism of the nanoparticle-formation reaction
      are also provided. It is just such studies that are the focus of the present
      work. Specifically, the present studies reveal that Pd(acac)2, in the presence of
      1 equiv of [Bu4N]2HPO4 as stabilizer in propylene carbonate, serves as a
      preferred precatalyst for the kinetically controlled nucleation following
      reduction under 40 +/- 1 psig initial H2 pressure at 22.0 +/- 0.1  degrees C to
      yield 7 +/- 2 nm palladium(0) nanoparticles. Studies of the balanced
      stoichiometry of the Pd(0)n nanoparticle-formation reaction shows that 1.0
      Pd(acac)2 consumes 1.0 equiv of H2 and produces 1.0 equiv of Pd(0)n while also
      releasing 2.0 +/- 0.2 equiv of acetylacetone. The inexpensive, readily available
      HPO4(2-) also proved to be as effective a Pd(0)n nanoparticle stabilizer as the
      more anionic, sterically larger, "Gold Standard" stabilizer P2W15Nb3O62(9-). The
      kinetics and associated minimal mechanism of formation of the [Bu4N]2HPO4
      stabilized Pd(0)n nanoparticles are also provided, arguably the most novel part
      of the present studies, specifically the four-step mechanism of nucleation (A ->
      B, rate constant k1), autocatalytic surface growth (A + B -> 2B, rate constant
      k2), bimolecular agglomeration (B + B -> C, rate constant k3), and secondary
      autocatalytic surface growth (A + C -> 1.5C, rate constant k4), where A is
      Pd(acac)2, B represents the growing, smaller Pd(0)n nanoparticles, and C
      represents the larger, most catalytically active Pd(0)n nanoparticles. Additional
      details on the mechanism and catalytic properties of the resultant Pd(0)n.HPO4(2
      ) nanoparticles are provided in this work. 

PMID- 27046306
TI  - Lori L. Altshuler, MD 1957-2015.
AB  - Lori L. Altshuler, MD, died on November 5, 2015, at her home in Manhattan Beach,
      California. It is easy to list Lori's many important contributions to psychiatry,
      but doing so describes only one facet of a wonderfully multidimensional and
      talented person. Yes, Lori held the Julia S. Gouw Endowed Chair in Mood Disorders
      at UCLA. 

PMID- 27046307
TI  - Toxoplasma gondii infection: relationship with aggression in psychiatric
      subjects.
AB  - OBJECTIVE: Toxoplasma gondii (T. gondii), a protozoan parasite that persists in
      host tissues, including brain, has been associated with several psychiatric
      disorders and with suicidal behavior. We sought to test the hypothesis that
      latent T. gondii infection, as manifest by circulating immunoglobulin G (IgG)
      antibodies to T. gondii, is associated with both categorical and dimensional
      measures of aggression. METHOD: IgG antibodies to T. gondii were collected
      between 1991 and 2008 from 358 adult subjects with DSM-5 intermittent explosive
      disorder (IED), non-IED psychiatric disorders (psychiatric controls), or no
      evidence of any psychiatric diagnosis (healthy controls). Assessments of
      aggression, anger, and impulsivity, as well as state/trait anger, depression, and
      anxiety were completed. T. gondii seropositive status (IgG > 12 IU) was the
      primary outcome measure for this study. RESULTS: T. gondii seropositive status
      (IgG > 12 IU) was associated with higher aggression (P = .022) and impulsivity (P
      = .05) scores. When both aggression and impulsivity scores were controlled for,
      however, only aggression scores were higher in seropositive subjects (P = .011).
      In addition, T. gondii seropositive status and marginal mean +/- SE aggression
      scores increased from healthy controls (9.1% and -0.66 +/- 0.05) to psychiatric
      controls (16.7% and -0.27 +/- 0.05) to subjects with IED (21.8% and 1.15 +/-
      0.06; P <= .05). These findings were not accounted for by the presence of other
      syndromal/personality disorders or by states or traits related to depressed or
      anxious moods. CONCLUSIONS: These data are consistent with previous studies
      suggesting a relationship between T. gondii and self-directed aggression (ie,
      suicidal behavior) and further add to the biological complexity of impulsive
      aggression both from a categorical and a dimensional perspective.

PMID- 27046308
TI  - Late-life exacerbation of PTSD symptoms in US veterans: results from the National
      Health and Resilience in Veterans Study.
AB  - OBJECTIVE: More than 60% of US military veterans are 55 years or older. Although
      several case studies have suggested that older age is associated with a higher
      likelihood of reactivated or delayed-onset posttraumatic stress disorder (PTSD)
      symptoms in veterans, population-based data on the prevalence and determinants of
      this phenomenon are lacking. METHOD: Using data from the National Health and
      Resilience in Veterans Study (NHRVS: Wave 1 = October 2011-December 2011; Wave 2
      = September 2013), a nationally representative, cohort study of US veterans, we
      evaluated the prevalence and determinants of exacerbated PTSD symptoms in 1,441
      veterans 55 years or older using a DSM-IV-based measure in 2011 and a DSM-5-based
      measure in 2013. Veterans whose worst trauma occurred at least 5 years prior to
      Wave 2 of the NHRVS (mean = 28.6 years) and who reported a clinically significant
      increase (ie, >= 0.5 standard deviation [SD]; mean = 1.27, SD = 0.78) in PTSD
      symptoms from Wave 1 (lifetime) to Wave 2 (past-month) were identified as having
      exacerbated PTSD symptoms. RESULTS: Results revealed that 9.9% of older US
      veterans experienced exacerbated PTSD symptoms an average of nearly 3 decades
      after their worst trauma. A multivariable logistic regression model indicated
      that greater self-reported cognitive difficulties at Wave 1 independently
      predicted exacerbated PTSD symptoms at Wave 2. Post hoc analysis revealed that
      this association was driven by greater severity of executive dysfunction
      (adjusted odds ratio range, 1.27-3.22). CONCLUSIONS: Approximately 1 in 10 older
      US veterans experiences a clinically significant exacerbation of PTSD symptoms in
      late life. Executive dysfunction may contribute to risk for exacerbated PTSD
      symptoms. These results suggest that exacerbated PTSD symptoms are prevalent in
      US veterans and highlight potential targets for identifying veterans at risk for
      this phenomenon.

PMID- 27046309
TI  - Efficacy and safety of adjunctive cariprazine in inadequate responders to
      antidepressants: a randomized, double-blind, placebo-controlled study in adult
      patients with major depressive disorder.
AB  - BACKGROUND: Cariprazine is an atypical antipsychotic currently under
      investigation as adjunctive therapy in patients with major depressive disorder
      (MDD) who have inadequate response to standard antidepressant therapy. METHOD: A
      randomized, double-blind, placebo-controlled, flexible-dose study was conducted
      from December 2011 to December 2013 in adults who met DSM-IV-TR criteria for MDD
      and had an inadequate antidepressant response. Eligible patients were randomized
      to 8-week adjunctive treatment with placebo (n = 269), cariprazine 1-2 mg/d (n =
      274), or cariprazine 2-4.5 mg/d (n = 276). The primary efficacy parameter was
      change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale
      (MADRS) total score; P values were adjusted for multiple comparisons. Safety
      assessments included adverse events, clinical laboratory tests, vital signs,
      electrocardiograms (ECGs), and suicidality. RESULTS: Compared with placebo,
      reduction in MADRS total score at week 8 was significantly greater with
      adjunctive cariprazine 2-4.5 mg/d (least squares mean difference [LSMD] = -2.2;
      adjusted P = .0114), but not with cariprazine 1-2 mg/d (LSMD = -0.9; adjusted P =
      .2404). Significant LSMDs for MADRS total score change were detected at all
      earlier study visits (weeks 2, 4, 6) in the 2- to 4.5-mg/d group and at weeks 2
      and 4 in the 1- to 2-mg/d group (all P values < .05). Treatment-emergent adverse
      events reported in >= 10% of patients in either cariprazine dosage group were
      akathisia (22.3%), insomnia (13.6%), and nausea (12.8%) (all in 2- to 4.5-mg/d
      group). Mean changes in metabolic parameters, vital signs, and ECG parameters
      were generally similar between groups. No suicide-related adverse events were
      reported. DISCUSSION: These results show that adjunctive cariprazine 2-4.5 mg/d
      was effective and generally well tolerated in adults with MDD who had inadequate
      responses to standard antidepressants. Further clinical studies to confirm these
      results are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01469377.

PMID- 27046310
TI  - Exaggerated acquisition and resistance to extinction of avoidance behavior in
      treated heroin-dependent men.
AB  - OBJECTIVE: Addiction is often conceptualized as a behavioral strategy for
      avoiding negative experiences. In rodents, opioid intake has been associated with
      abnormal acquisition and extinction of avoidance behavior. Here, we tested the
      hypothesis that these findings would generalize to human opioid-dependent
      subjects. METHOD: Adults meeting DSM-IV criteria for heroin dependence and
      treated with opioid medication (n = 27) and healthy controls (n = 26) were
      recruited between March 2013 and October 2013 and given a computer-based task to
      assess avoidance behavior. For this task, subjects controlled a spaceship and
      could either gain points by shooting an enemy spaceship or hide in safe areas to
      avoid on-screen aversive events. Hiding duration during different periods of the
      task was used to measure avoidance behavior. RESULTS: While groups did not differ
      on escape responding (hiding) during the aversive event, heroin-dependent men
      (but not women) made more avoidance responses during a warning signal that
      predicted the aversive event (analysis of variance, sex * group interaction, P =
      .007). Heroin-dependent men were also slower to extinguish the avoidance response
      when the aversive event no longer followed the warning signal (P = .011). This
      behavioral pattern resulted in reduced opportunity to obtain reward without
      reducing risk of punishment. Results suggest that, in male patients, differences
      in avoidance behavior cannot be easily explained by impaired task performance or
      by exaggerated motor activity. CONCLUSIONS: This study provides evidence for
      abnormal acquisition and extinction of avoidance behavior in opioid-dependent
      patients. Interestingly, data suggest that abnormal avoidance is demonstrated
      only by male patients. Findings shed light on cognitive and behavioral
      manifestations of opioid addiction and may facilitate development of therapeutic
      approaches to help affected individuals.

PMID- 27046311
TI  - Playing it safe: a video game probing the relationship between addiction, gender,
      and avoidance.

PMID- 27046312
TI  - Efficacy of topiramate in the treatment of crack cocaine dependence: a double
      blind, randomized, placebo-controlled trial.
AB  - OBJECTIVE: We performed a double-blind, randomized, placebo-controlled trial to
      assess the efficacy of topiramate in the treatment of crack cocaine dependence.
      METHOD: Sixty men who were dependent on cocaine (DSM-IV) (exclusive use of crack
      cocaine) were selected. The subjects were randomly assigned to either a
      topiramate group (subjects received 50-200 mg of topiramate per day for 12 weeks)
      or a control group (subjects received placebo). The initial daily treatment dose
      was 50 mg, and this dose was increased weekly at increments of 25 to 50 mg, based
      on the subject's tolerability, to a maximum of 200 mg. All of the subjects also
      participated in motivational interviews and group therapy. The primary outcome
      measures were detection of benzoylecgonine in the urine, study retention,
      frequency of cocaine smoking, amount of cocaine use, and mean amount of money
      spent on cocaine per week. The study was conducted from February 2013 to February
      2014. RESULTS: Twenty-nine subjects in the topiramate group and 29 subjects in
      the control group completed the study. Longitudinal assessment revealed that
      retention was not significant (odds ratio [OR] = 1.072, P = .908) between the 2
      groups. Negative results from a urine test for benzoylecgonine (a cocaine
      metabolite), which is a measure of cocaine abstinence, were more frequently
      obtained from the topiramate group (OR = 8.687, P < .001). Topiramate reduced the
      quantity of cocaine used (mean reduction = -3.108 g, P < .001), the frequency of
      cocaine use (mean = -0.784 times per week, P = .005), and the amount of money
      spent on cocaine (mean [US dollars] = -$25.38, P = .015; this variable did not
      achieve statistical significance after Bonferroni correction) compared with the
      placebo during the 12 weeks (or 84 days) of the assessment. However, the
      differences in reductions between the 2 groups in the quantity of cocaine used,
      the frequency of cocaine use, and money spent on cocaine over time (time * group
      interaction) were present only during the first 4 weeks, and none of these
      variables by 12 weeks. The studied groups did not differ with regard to secondary
      end points, such as study dropout and the number of subjects who reported side
      effects. CONCLUSIONS: The present findings indicate that topiramate is effective
      and safe and thus reinforce previous data suggesting that topiramate is a
      potentially useful treatment for crack cocaine dependence. However, we found that
      topiramate is only useful as an adjunctive treatment during the first 4 weeks of
      the treatment. Future studies with larger samples are needed to confirm these
      results. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clinicos (ReBEC) RBR
      3vwfjs and UTN: U1111-1131-4443.

PMID- 27046313
TI  - Confidence in the "Iron Dome" missile defense system combined with a sense of
      resilience reduced the effect of exposure on posttraumatic stress disorder
      symptoms after missile attacks.

PMID- 27046314
TI  - Can exposure-based CBT extend the effects of intravenous ketamine in obsessive
      compulsive disorder? an open-label trial.

PMID- 27046315
TI  - Use of acetaminophen (paracetamol) during pregnancy and the risk of attention
      deficit/hyperactivity disorder in the offspring.
AB  - Prenatal exposure to acetaminophen may result in compromised neurodevelopment
      through inflammatory and immunologic mechanisms, through predisposition to
      oxidative stress, and through endocrine, endogenous cannabinoid, and other
      mechanisms. Several small and large prospective studies have found an association
      between gestational acetaminophen exposure and attention-deficit/hyperactivity
      disorder (ADHD)-like behaviors, use of ADHD medication, and ADHD diagnoses in
      offspring during childhood; the only negative study was a small investigation
      that examined only one aspect of attention as an outcome. Creditably, most of the
      studies adjusted analyses for many (but not all) confounds associated with ADHD
      risk. Importantly, one pivotal study also adjusted for pain, infection,
      inflammation, and fever to reduce confounding by indication; this study found a
      dose-dependent risk. In the light of the finding of a single study that infection
      and fever during pregnancy by themselves do not raise the ADHD risk, it appears
      possible that the use of acetaminophen during pregnancy is itself responsible for
      the increased risk of ADHD. This suggests that acetaminophen may not be as safe
      in pregnancy as is widely believed. However, since fever during pregnancy may
      itself be associated with adverse gestational outcomes, given the present level
      of uncertainty about the ADHD risk with acetaminophen, it is suggested that,
      until more data are available, the use of acetaminophen in pregnancy should not
      be denied in situations in which the need for the drug is clear. 

PMID- 27046316
TI  - The ABCs of CNS stimulant misuse.

PMID- 27046317
TI  - Correction. Effects of Aripiprazole on the QTc: A Case Report.

PMID- 27046318
TI  - The benefits of measurement-based care for primary care patients with depression.
AB  - Follow the case of Mrs C, a primary care patient with depression who fails to
      respond to initial antidepressant treatment, and see how measurement-based care
      helps her clinician confirm her diagnosis, track symptom response, and assess her
      sense of well-being. Using rating scales such as the 9-item Patient Health
      Questionnaire (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7), and
      Mood Disorder Questionnaire (MDQ) can help clinicians recognize suboptimal
      response and make treatment adjustments such as optimizing the medication dose,
      switching to another medication, or augmenting with medications, psychotherapy,
      or exercise. For Mrs C and other patients with depression, the goal of treatment
      must go beyond symptom remission to improve quality of life. 

PMID- 27046319
TI  - Neurobiology of depression and mechanism of action of depression treatments.
AB  - Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), may
      alleviate depressive symptoms but also leave residual symptoms. The mechanism of
      action of SSRIs increases serotonin (5-HT) activity but decreases norepinephrine
      (NE) and dopamine (DA) activity. By engaging additional targets (eg, NE, DA)
      along with 5-HT, clinicians may help patients with residual symptoms and
      treatment-resistant depression. Dual-acting agents and combination strategies can
      be used to target specific symptoms or block/activate specific receptors for
      broader therapeutic benefits. Clinicians who understand the mechanism of action
      of antidepressants can switch or combine agents as needed to help patients
      achieve complete remission. 

PMID- 27046320
TI  - Weight gain and 10-year cardiovascular risk with sustained tobacco abstinence in
      smokers with serious mental illness: a subgroup analysis of a randomized trial.
AB  - OBJECTIVE: People with serious mental illness die earlier than those without
      mental illness, largely from cardiovascular disease due to high rates of smoking
      and obesity. The objective of this study was to determine whether the metabolic
      effects of postcessation weight gain among smokers with serious mental illness
      attenuated the cardiovascular benefit of tobacco abstinence. METHOD: A subgroup
      analysis was conducted of 65 outpatient smokers with DSM-IV diagnosis of
      schizophrenia, schizoaffective disorder, or bipolar disorder from 10 community
      mental health centers in 6 states who enrolled between March 2008-April 2012 and
      completed a trial of varenicline for tobacco abstinence. The intervention
      included a 12-week open-label phase with varenicline followed by a 40-week
      randomized, placebo-controlled phase in 87 participants who achieved 12-week
      abstinence. Main outcome measures were smoking status and change from baseline in
      weight and 10-year Framingham cardiovascular risk score at end of intervention
      (week 52). RESULTS: At week 52, 65 participants completed follow-up (33
      abstinent; 32 relapsed). At baseline, the 2 groups did not differ in body mass
      index (mean = 31 kg/m(2)), blood pressure, serum glucose, or diagnoses of
      diabetes (31%) and hypertension (34%). Abstinent participants were older and had
      a higher mean baseline Framingham risk score (14.2% vs 10.3%, P = .002). At week
      52, abstinent participants gained more weight than relapsed participants (4.8 vs
      1.2 kg, P = .048) and, as a result of quitting smoking, had a greater reduction
      in Framingham risk score (-7.6% vs 0.0%, P < .001). There was no effect of study
      drug assignment on weight or Framingham risk score. CONCLUSIONS: Sustained
      tobacco abstinence reduced 10-year cardiovascular risk in outpatients with
      serious mental illness despite significant postcessation weight gain and high
      prevalence of obesity, diabetes, and hypertension. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT00621777.

PMID- 27046321
TI  - The dual epidemic of tobacco dependence and obesity among those with severe
      mental illness.

PMID- 27046322
TI  - Cardiorespiratory fitness in outpatients with bipolar disorder versus matched
      controls: An exploratory study.
AB  - BACKGROUND: Patients with bipolar disorder (BD) are approximately twice as likely
      to die prematurely due cardiovascular diseases (CVD) than the general population.
      Cardiorespiratory fitness (CRF) is an important health outcome measure,
      predictive for CVD and premature mortality. AIMS: The aim of the current study
      was to compare the CRF of outpatients with BD versus age-, gender-, and body mass
      index (BMI)-matched healthy controls (HC). A secondary aim was to assess
      potential correlates of CRF. METHODS: All participants underwent a maximal
      incremental exercise test to measure the maximum oxygen uptake (VO2max, the
      golden standard assessment of cardiorespiratory fitness), wore a Body Sensewear
      Armband for 5 subsequent days to assess their physical activity behavior and
      completed the Positive-and-Negative-Affect-Schedule (PANAS). RESULTS: Outpatients
      with BD (n=20; 47.8+/-7.6years) had a significantly lower VO2max compared with HC
      (n=20; 47.8+/-7.6years) (26.0+/-7.3 versus 30.4+/-6.5ml/min/kg, P=0.047). A
      higher VO2max was correlated with younger age, higher active energy expenditure,
      higher PANAS positive and lower PANAS negative affect scores and a lower
      antipsychotic medication dose. LIMITATIONS: The limited sample and cross
      sectional design preclude definitive conclusions. CONCLUSIONS: Compared with HC,
      outpatients with BD have reduced CRF levels of approximately 4.4ml/min/kg. In the
      general population such reductions are associated with a 20% increased premature
      mortality risk. Interventions targeting CRF in BD are required. Although more
      research is needed, clinicians should consider the utility of objective
      assessments of CRF for risk stratification in outpatient settings.

PMID- 27046323
TI  - Low-voltage, high-brightness and deep-red light-emitting electrochemical cells
      (LECs) based on new ruthenium(ii) phenanthroimidazole complexes.
AB  - Light-Emitting Electrochemical Cells (LECs) with a simple device structure ITO/Ru
      complex/Ga:In were prepared by using heteroleptic ruthenium(ii) complexes
      containing 2-(2-hydroxyphenyl)-1-(4-bromophenyl)-1h-imidazo[4,5
      f][1,10]phenanthroline (hpbpip) as the pi-extended ligand. After ancillary ligand
      modification, the [Ru(hpbpip)(dmbpy)2](ClO4)2 complex shows a deep red
      electroluminescence emission (2250 cd m(-2) at 6 V) centered at 685 nm, 65 nm red
      shifted compared to the [Ru(bpy)3](ClO4)2 benchmark red-emitter at a very low
      turn voltage (2.6 V), demonstrating its potential for low-cost deep-red light
      sources. Moreover, the PL quantum yield of the [Ru(hpbpip)(bpy)2](ClO4)2 complex
      was revealed to be higher (0.121) than the benchmark standard [Ru(bpy)3](2+)
      (0.095).

PMID- 27046324
TI  - Monte-Carlo model development for evaluation of current clinical target volume
      definition for heterogeneous and hypoxic glioblastoma.
AB  - Clinical target volume (CTV) determination may be complex and subjective. In this
      work a microscopic-scale tumour model was developed to evaluate current CTV
      practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a
      Geant4 cell-based dosimetry model was developed to calculate the dose deposited
      in individual GBM cells. Microscopic extension probability (MEP) models were then
      developed using Matlab-2012a. The results of the cell-based dosimetry model and
      MEP models were combined to calculate survival fractions (SF) for CTV margins of
      2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous
      radiosensitivity profiles were incorporated into the GBM model. The genetic
      heterogeneity was modelled using a range of alpha/beta values (linear-quadratic
      model parameters) associated with different GBM cell lines. These values were
      distributed among the cells randomly, taken from a Gaussian-weighted sample of
      alpha/beta values. Cellular oxygen pressure was distributed randomly taken from a
      sample weighted to profiles obtained from literature. Three types of GBM models
      were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous
      hypoxic. The SF in different regions of the tumour model and the effect of the
      CTV margin extension from 2.0-2.5 cm on SFs were investigated for three MEP
      models. The SF within the beam was increased by up to three and two orders of
      magnitude following incorporation of heterogeneous radiosensitivities and
      hypoxia, respectively, in the GBM model. However, the total SF was shown to be
      overdominated by the presence of tumour cells in the penumbra region and to a
      lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm
      reduced the SF by a maximum of 78.6  +/-  3.3%, 78.5  +/-  3.3%, and 77.7  +/- 
      3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs,
      respectively. Monte-Carlo model was developed to quantitatively evaluate SF for
      genetically heterogeneous and hypoxic GBM with two CTV margins and three MEP
      distributions. The results suggest that photon therapy may not provide cure for
      hypoxic and genetically heterogeneous GBM. However, the extension of the CTV
      margin by 0.5 cm could be beneficial to delay the recurrence time for this tumour
      type due to significant increase in tumour cell irradiation.

PMID- 27046325
TI  - Sterol-Phospholipid Hybrids at the Air/Water Interface: Studies on Properties and
      Interactions with Parent Lipid Molecules.
AB  - The two synthetic sterol-phospholipid hybrids DCholPC and PCholPC were
      investigated in monolayers at the air/water interface. Study was based on pi-A
      isotherm analysis complemented with application of grazing incidence X-ray
      diffraction. It was found that both compounds are capable of forming stable,
      highly condensed monolayers of a surface characteristics typical for sterols.
      GIXD studies show that the crystallographic area for DCholPC monolayer is very
      similar to that found for cholesterol (37.1 vs 38.0 A(2)), while for PCholPC
      (28.8 A(2)) it is significantly smaller as compared to area for the mixed
      Chol/DPPC 2/1 monolayer (33.4 A(2)). In our study the problem of interactions
      between investigated sterol-phospholipid hybrids and natural membrane lipid
      components was for the first time analyzed in planar lipid systems. Studies on
      mixed monolayers showed that both hybrids, similarly to cholesterol, reveal a
      condensing effect toward DPPC acyl chains; however, DCholPC having two steroid
      moieties in the molecule was found to be more efficient. On the other hand, the
      sterol moiety and the hydrocarbon chain of PCholPC molecule are packed in the 2D
      crystalline phase extremely tight. Our studies showed that the investigated
      compounds can be applied as biocompatible components of stable liposomes.

PMID- 27046326
TI  - A prospective study of genetic factors, human laboratory phenotypes, and heavy
      drinking in late adolescence.
AB  - Subjective responses to alcohol are considered candidate endophenotypes for
      alcohol use disorder and appear to anticipate future consumption. However,
      prospective studies have been rare, and laboratory research has typically
      examined subjective responses absent measures of self-administration. This study
      examined the association of subjective responses with subsequent laboratory self
      administration, also evaluating laboratory phenotypes in relation to putative
      genetic risk factors [family history (FH) of alcohol dependence and OPRM1
      genotype] and subsequent heavy drinking. Participants (N = 61, M = 19.89 years,
      SD = 0.86) completed laboratory sessions involving intravenous alcohol challenge
      (Session 1) and free-access intravenous self-administration (Session 2), followed
      by prospective assessments. Multilevel modeling showed that higher reported
      stimulation and lower sedation during Session 1 independently predicted greater
      alcohol self-administration during Session 2. Although self-administration did
      not differ by FH group, participants with the OPRM1 118G allele evidenced steeper
      breath alcohol concentration (BrAC) trajectories and greater peak BrAC relative
      to 118A homozygous participants. Prospective analyses supported significant
      indirect associations between Session 1 subjective responses and 6-month heavy
      drinking via peak BrAC in Session 2. Additionally, significant indirect
      associations of FH (via Session 1 stimulation and Session 2 peak BrAC) and OPRM1
      (via peak BrAC) with follow-up heavy drinking were observed. These results
      further support the utility of human laboratory phenotypes in prospective studies
      of alcohol use disorder risk and highlight the potential role of self
      administration phenotypes in longitudinal research.

PMID- 27046327
TI  - BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION: A CASE REPORT.
AB  - PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation
      (BDUMP) in the setting of metastatic ovarian cancer. METHODS: In this
      observational case report, a 59-year-old woman presented with bilateral worsening
      vision and photophobia. She had been diagnosed with metastatic ovarian cancer 5
      years prior for which she received Tamoxifen. Ophthalmic examination was
      completed followed by fluorescein angiography and optical coherence tomography
      (Spectralis OCT; Heidelberg Engineering). RESULTS: The visual acuity was 20/150
      in both eyes. Exam demonstrated an iris pigmented lesion in the right eye,
      bilateral nuclear sclerotic cataracts, multiple orange lesions in the fundus,
      elevated pigmented uveal melanocytic tumors with diffuse choroidal thickening and
      multifocal early hyperfluorescence of these lesions (giraffe-like pattern) on
      fluorescein angiography, and exudative retinal detachment on OCT. The patient was
      diagnosed with BDUMP in the setting of metastatic ovarian carcinoma. Further
      metastatic workup demonstrated enlarged lymphadenopathy in the right axilla and
      inguinal regions. The patient declined chemotherapy and was initiated on
      plasmapheresis. CONCLUSIONS: BDUMP is a peculiar paraneoplastic syndrome in the
      setting of metastatic ovarian cancer, where antigens from the retinal pigment
      epithelium, iris and choroidal melanocytes cross-react with ovarian tumor cell
      antibodies that are circulating in the serum. Plasmapheresis can decrease the
      concentrations of the antibodies, maintain reasonable functional vision and
      improve the quality of life.

PMID- 27046328
TI  - Change in Experiential Avoidance is Associated with Reduced Suicidal Ideation
      over the Course of Psychiatric Hospitalization.
AB  - Growing empirical literature in recent years indicates that experiential
      avoidance plays a role in a wide variety of psychological disorders and
      psychotherapeutic interventions. This study explored the view of suicidal
      ideation as a form of experiential avoidance by examining the association between
      suicidal ideation and therapeutic change in a sample of 189 adult psychiatric
      inpatients. Results were consistent with predictions, showing a statistically
      significant association between scores on the Beck Scale for Suicidal Ideation
      and the Acceptance and Action Questionnaire-II (AAQ-II). It was further shown
      that change in AAQ-II scores over the course of hospitalization was associated
      with change in suicidality, independent of changes in depression severity and
      hopelessness. Moreover, treatment responders (patients whose suicidal ideation
      scores dropped significantly over the course of treatment) showed greater drops
      in experiential avoidance relative to nonresponders. These results are consistent
      with a view of suicidal ideation (and, by extension, suicide) as a form of
      experiential avoidance and potentially a therapeutic approach that specifically
      seeks to reduce experiential avoidance.

PMID- 27046329
TI  - Molecular Inversion Probes for targeted resequencing in non-model organisms.
AB  - Applications that require resequencing of hundreds or thousands of predefined
      genomic regions in numerous samples are common in studies of non-model organisms.
      However few approaches at the scale intermediate between multiplex PCR and
      sequence capture methods are available. Here we explored the utility of Molecular
      Inversion Probes (MIPs) for the medium-scale targeted resequencing in a non-model
      system. Markers targeting 112 bp of exonic sequence were designed from
      transcriptome of Lissotriton newts. We assessed performance of 248 MIP markers in
      a sample of 85 individuals. Among the 234 (94.4%) successfully amplified markers
      80% had median coverage within one order of magnitude, indicating relatively
      uniform performance; coverage uniformity across individuals was also high. In the
      analysis of polymorphism and segregation within family, 77% of 248 tested MIPs
      were confirmed as single copy Mendelian markers. Genotyping concordance assessed
      using replicate samples exceeded 99%. MIP markers for targeted resequencing have
      a number of advantages: high specificity, high multiplexing level, low sample
      requirement, straightforward laboratory protocol, no need for preparation of
      genomic libraries and no ascertainment bias. We conclude that MIP markers provide
      an effective solution for resequencing targets of tens or hundreds of kb in any
      organism and in a large number of samples. 

PMID- 27046330
TI  - A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in
      the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia.
AB  - BACKGROUND: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to
      nerve damage and preventable disability affecting hands, feet and eyes. Type 1
      Reactions are treated with oral corticosteroids. There is little evidence on
      alternative treatments for patients who do not respond to steroids or experience
      steroid adverse effects. We report the results of a randomized controlled trial
      testing the efficacy and adverse effect profile of ciclosporin and prednisolone
      (CnP) in comparison to prednisolone only (P) in patients with new T1R in
      Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using
      a clinical severity score, recurrence rate, adverse events and quality of life.
      RESULTS: Seventy three patients with new T1R were randomized to receive CnP or P
      for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs
      88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and
      motor (75% vs 74%) loss were higher (but not significantly so) in the patients on
      CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences
      occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more
      additional prednisolone. Serious major and minor adverse events rates were
      similar in patients in the two treatment arms of the study. Both groups had a
      significant improvement in their quality of life after the study, measured by the
      SF-36. CONCLUSIONS: This is the first double-blind RCT assessing ciclosporin, in
      the management of T1R in Africa. Ciclosporin could be a safe alternative second
      line drug for patients with T1R who are not improving with prednisolone or are
      experiencing adverse events related to prednisolone. This study illustrates the
      difficulty in switching off leprosy inflammation. Better treatment agents for
      leprosy patients with reactions and nerve damage are needed.

PMID- 27046332
TI  - Corrigendum.

PMID- 27046331
TI  - Minimally Invasive Esophagectomy: A New Era of Surgical Resection.
AB  - Adenocarcinoma of the esophagus continues to increase in incidence and has become
      a significant health problem in Western countries. While mortality rates are
      slowly improving from this disease, multimodality treatment, including
      esophagectomy, has remained critical for optimal outcomes. Esophagectomy has been
      described as an operation with significant morbidity and mortality, but over the
      last decade, increased utilization of minimally invasive esophagectomy in an
      effort to reduce the high rates of morbidity and lengthy hospital stays
      associated with open esophagectomy has been adopted at many medical centers. We
      review esophageal cancer treatment modalities, considerations in the current
      context of neoadjuvant therapy, and increased adoption of minimally invasive
      approaches. 

PMID- 27046333
TI  - Topical anti-inflammatory phytomedicine based on Sphagneticola trilobata dried
      extracts.
AB  - CONTEXT: The aerial parts of Sphagneticola trilobata (L.) Pruski (Asteraceae) are
      popularly used to treat topical inflammation, but have not been fully
      investigated. OBJECTIVE: To identify polar compounds in S. trilobata extracts and
      develop a new topical phytomedicine based on the kaurenoic acid (KA) content
      while monitoring and demonstrating its topical anti-inflammatory activity.
      MATERIALS AND METHODS: Ethanol spray-dried extract of S. trilobata was analysed
      by LC-MS while the KA content from semisolid was analysed by LC-UV. The extent of
      ear edema induced by applying 20 MUL of croton oil (2.5%), arachidonic acid (AA;
      2 mg/ear) and decanoylphorbol-13-acetate (TPA; 2.5 mg/ear) in mice was used to
      evaluate the biological activity of the semisolids, which were applied 30 min
      before the phlogistic agents. RESULTS: Eight phenylpropanoids and four oleanane
      type triterpenoid saponins were identified, majority of them reported for the
      first time in this species, in addition to KA. The semisolid containing 1.0% of
      dried extract reduced the ear edema induced by croton oil [77.2 +/- 4.5%; ID50 =
      0.49 (0.28-0.87%)], TPA (81.5 +/- 2.4%) and AA (39.1 +/- 6.9%), with decreasing
      effect at higher KA concentrations. This was accompanied by neutrophil migration
      inhibition as investigated by biochemical and histological assays. DISCUSSION AND
      CONCLUSION: The anti-inflammatory effects were (at least in part) due to the
      interference in protein kinase C (PKC) activation, AA-cascade products and
      neutrophil migration inhibition, demonstrating the efficacy of the folk topical
      usage of this plant. The results support the development of a novel topical anti
      inflammatory phytomedicine properly standardized to treat inflammatory
      dermatological diseases.

PMID- 27046334
TI  - A barrier to homologous recombination between sympatric strains of the
      cooperative soil bacterium Myxococcus xanthus.
AB  - The bacterium Myxococcus xanthus glides through soil in search of prey microbes,
      but when food sources run out, cells cooperatively construct and sporulate within
      multicellular fruiting bodies. M. xanthus strains isolated from a 16 * 16-cm
      scale patch of soil were previously shown to have diversified into many distinct
      compatibility types that are distinguished by the failure of swarming colonies to
      merge upon encounter. We sequenced the genomes of 22 isolates from this
      population belonging to the two most frequently occurring multilocus sequence
      type (MLST) clades to trace patterns of incipient genomic divergence,
      specifically related to social divergence. Although homologous recombination
      occurs frequently within the two MLST clades, we find an almost complete absence
      of recombination events between them. As the two clades are very closely related
      and live in sympatry, either ecological or genetic barriers must reduce genetic
      exchange between them. We find that the rate of change in the accessory genome is
      greater than the rate of amino-acid substitution in the core genome. We identify
      a large genomic tract that consistently differs between isolates that do not
      freely merge and therefore is a candidate region for harbouring gene(s)
      responsible for self/non-self discrimination.

PMID- 27046335
TI  - Genetic diversity affects ecological performance and stress response of marine
      diatom populations.
AB  - Genetic diversity is considered an important factor, stabilizing ecological
      functions when organisms are faced with changing environmental conditions.
      Although well known from terrestrial systems, documentations of this relationship
      from marine organisms, and particularly planktonic microorganisms, are still
      limited. Here we experimentally tested the effects of genotypic diversity on
      ecologically relevant cellular parameters (growth, primary production,
      particulate organic carbon, particulate organic nitrogen, particulate organic
      phosphorus and biogenic silica) at optimal and suboptimal salinity conditions in
      a marine phytoplankton species. Multiple clonal genotyped and phenotypically
      characterized isolates of the diatom Skeletonema marinoi from the Baltic Sea were
      grown in monocultures and mixes of 5 and 20 clones at native (5 psu) and reduced
      (3 psu) salinities and respective parameters were compared. Re-genotyping of 30
      individuals from each population at five microsatellite loci at the end of the
      experiment confirmed maintenance of genotypic richness. Although a diversity
      effect on growth was not detected, primary production and particulate organic
      nutrients were positively affected by increased diversity independent of salinity
      condition. Under salinity stress, highest values of primary production and
      particulate organic nitrogen content were measured at the high diversity level.
      The observed diversity effects emphasize the importance of genetic diversity of
      phytoplankton populations for ecological functions.

PMID- 27046336
TI  - Evolutionary tradeoffs in cellular composition across diverse bacteria.
AB  - One of the most important classic and contemporary interests in biology is the
      connection between cellular composition and physiological function. Decades of
      research have allowed us to understand the detailed relationship between various
      cellular components and processes for individual species, and have uncovered
      common functionality across diverse species. However, there still remains the
      need for frameworks that can mechanistically predict the tradeoffs between
      cellular functions and elucidate and interpret average trends across species.
      Here we provide a comprehensive analysis of how cellular composition changes
      across the diversity of bacteria as connected with physiological function and
      metabolism, spanning five orders of magnitude in body size. We present an
      analysis of the trends with cell volume that covers shifts in genomic, protein,
      cellular envelope, RNA and ribosomal content. We show that trends in protein
      content are more complex than a simple proportionality with the overall genome
      size, and that the number of ribosomes is simply explained by cross-species
      shifts in biosynthesis requirements. Furthermore, we show that the largest and
      smallest bacteria are limited by physical space requirements. At the lower end of
      size, cell volume is dominated by DNA and protein content-the requirement for
      which predicts a lower limit on cell size that is in good agreement with the
      smallest observed bacteria. At the upper end of bacterial size, we have
      identified a point at which the number of ribosomes required for biosynthesis
      exceeds available cell volume. Between these limits we are able to discuss
      systematic and dramatic shifts in cellular composition. Much of our analysis is
      connected with the basic energetics of cells where we show that the scaling of
      metabolic rate is surprisingly superlinear with all cellular components.

PMID- 27046338
TI  - Activation of Peroxisome Proliferator-activated Receptor gamma Prevents
      Development of Heart Failure With Preserved Ejection Fraction; Inhibition of Wnt
      beta-catenin Signaling as a Possible Mechanism.
AB  - Left ventricular (LV) fibrosis plays an important role in the development of
      heart failure with preserved ejection fraction (HFpEF). We investigated whether
      chronic peroxisome proliferator-activated receptor gamma agonism with
      pioglitazone can prevent the development of HFpEF. We also evaluated the role of
      Wnt-beta-catenin signaling in the development of HFpEF, and its relationship to
      peroxisome proliferator-activated receptor gamma signaling. Dahl salt-sensitive
      rats placed on an 8% NaCl diet from age 6 weeks were used as HFpEF model. Rats
      placed on 0.3% NaCl diet served as controls (n = 7). HFpEF model rats were
      randomized to no treatment (n = 7) or treatment with pioglitazone (2.5 mg/kg per
      day, n = 7) at age 13 weeks. Pioglitazone administration from age 13 to 21 weeks
      attenuated the development of LV fibrosis and stiffening (both P < 0.05), and
      subsequently prevented the development of HFpEF. In the untreated HFpEF model,
      Wnt1, 2, 10b messenger RNA and beta-catenin protein expression levels in the left
      ventricle increased in the heart failure stage, along with the increase in type I
      collagen messenger RNA expression levels. Administration of pioglitazone
      attenuated the activation of Wnt-beta-catenin signaling. Our results show that
      pioglitazone prevented the development of LV fibrosis and HFpEF in a rat model,
      at least partly due to attenuated Wnt-beta-catenin signaling. 

PMID- 27046337
TI  - N-Methyl-D-Aspartate Receptor Signaling and Function in Cardiovascular Tissues.
AB  - Excellent reviews on central N-methyl-D-aspartate receptor (NMDAR) signaling and
      function in cardiovascular regulating neuronal pools have been reported. However,
      much less attention has been given to NMDAR function in peripheral tissues,
      particularly the heart and vasculature, although a very recent review discusses
      such function in the kidney. In this short review, we discuss the NMDAR
      expression and complexity of its function in cardiovascular tissues. In conscious
      (contrary to anesthetized) rats, activation of the peripheral NMDAR triggers
      cardiovascular oxidative stress through the PI3K-ERK1/2-NO signaling pathway,
      which ultimately leads to elevation in blood pressure. Evidence also implicates
      Ca release, in the peripheral NMDAR-mediated pressor response. Despite evidence
      of circulating potent ligands (eg, D-aspartate and L-aspartate, L-homocysteic
      acid, and quinolinic acid) and also their coagonist (eg, glycine or D-serine),
      the physiological role of peripheral cardiovascular NMDAR remains elusive.
      Nonetheless, the cardiovascular relevance of the peripheral NMDAR might become
      apparent when its signaling is altered by drugs, such as alcohol, which interact
      with the NMDAR or its downstream signaling mechanisms. 

PMID- 27046339
TI  - Combination Therapy With Coenzyme Q10 and Trimetazidine in Patients With Acute
      Viral Myocarditis.
AB  - BACKGROUND: Acute viral myocarditis is an inflammatory disease with global
      impact. Although it may resolve spontaneously, its course is not easily
      predicted, and there is a paucity of specific treatment options available with
      proven efficacy. Coenzyme Q10 (CQ10) and trimetazidine possess antioxidant and
      antiinflammatory effects. METHODS: We examined the therapeutic efficacy of these
      agents in acute viral myocarditis both individually and in combination. Patients
      were blinded and randomized to receive CQ10 (n = 42), trimetazidine (n = 39), or
      CQ10 + trimetazidine (n = 43) treatment. RESULTS: Serum inflammatory and
      oxidative stress marker and myocardial enzyme levels, and heart function were
      measured. Both CQ10 and trimetazidine decreased inflammatory and oxidative stress
      biomarker levels compared with baseline measurements. However, combination
      therapy with CQ10 and trimetazidine showed a significantly more powerful effect
      not only on markers of inflammation and oxidative stress, but also on left
      ventricular systolic function and troponin, compared with either treatment alone.
      CONCLUSION: This study confirmed the beneficial effect of CQ10 and trimetazidine
      individually, but demonstrated a superior effect of combining the therapies on
      cardiac left ventricular ejection fraction, and biochemical markers of myocardial
      damage in acute viral myocarditis.

PMID- 27046340
TI  - Cold plasma inactivation of chronic wound bacteria.
AB  - Cold plasma is partly ionized non-thermal plasma generated at atmospheric
      pressure. It has been recognized as an alternative approach in medicine for
      sterilization of wounds, promotion of wound healing, topical treatment of skin
      diseases with microbial involvement and treatment of cancer. Cold plasma used in
      wound therapy inhibits microbes in chronic wound due to its antiseptic effects,
      while promoting healing by stimulation of cell proliferation and migration of
      wound relating skin cells. In this study, two types of plasma systems are
      employed to generate cold plasma: a parallel plate dielectric barrier discharge
      and a capillary-guided corona discharge. Parameters such as applied voltage,
      discharge frequency, treatment time and the flow of the carrier gas influence the
      cold plasma chemistry and therefore change the composition and concentration of
      plasma species that react with the target sample. Chronic wound that fails to
      heal often infected by multidrug resistant organisms makes them recalcitrant to
      healing. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas
      aeruginosa (Pseudomonas aeruginosa) are two common bacteria in infected and
      clinically non-infected wounds. The efficacies of the cold plasma generated by
      the two designs on the inactivation of three different isolates of MRSA and four
      isolates of P. aeruginosa are reported here.

PMID- 27046342
TI  - Activation of zinc-requiring ectoenzymes by ZnT transporters during the secretory
      process: Biochemical and molecular aspects.
AB  - In humans, about 1000 enzymes are estimated to bind zinc. In most of these
      enzymes, zinc is present at the active site; thus, these enzymes are functional
      as "zinc-requiring enzymes". Of these zinc-requiring enzymes, zinc-requiring
      ectoenzymes (defined as secretory, membrane-bound, and organelle-resident
      enzymes) have received much attention because of their important physiological
      functions, involvement in a number of diseases, and potential applications as
      therapeutic targets for diseases. Zinc-requiring ectoenzymes may become active by
      coordinating zinc at their active site during the secretory process, which
      requires elaborate control of zinc mobilization from the extracellular milieu to
      the cytosol and then lumen in the early secretory pathway. Therefore, zinc
      transporters should properly maintain the process at systemic, cellular, and
      subcellular levels by mobilizing zinc across biological membranes. However, few
      studies have examined the mechanisms underlying this process. In this review,
      current knowledge of the activation process of zinc-requiring ectoenzymes by ZnT
      zinc transporters in the early secretory pathway is briefly reviewed at the
      molecular level, with a focus on tissue-nonspecific alkaline phosphatase.
      Moreover, we also discuss whether zinc-chaperone proteins function during the
      activation of these enzymes.

PMID- 27046341
TI  - Current advances in synchrotron radiation instrumentation for MX experiments.
AB  - Following pioneering work 40 years ago, synchrotron beamlines dedicated to
      macromolecular crystallography (MX) have improved in almost every aspect as
      instrumentation has evolved. Beam sizes and crystal dimensions are now on the
      single micron scale while data can be collected from proteins with molecular
      weights over 10 MDa and from crystals with unit cell dimensions over 1000 A.
      Furthermore it is possible to collect a complete data set in seconds, and obtain
      the resulting structure in minutes. The impact of MX synchrotron beamlines and
      their evolution is reflected in their scientific output, and MX is now the method
      of choice for a variety of aims from ligand binding to structure determination of
      membrane proteins, viruses and ribosomes, resulting in a much deeper
      understanding of the machinery of life. A main driving force of beamline
      evolution have been advances in almost every aspect of the instrumentation
      comprising a synchrotron beamline. In this review we aim to provide an overview
      of the current status of instrumentation at modern MX experiments. The most
      critical optical components are discussed, as are aspects of endstation design,
      sample delivery, visualisation and positioning, the sample environment, beam
      shaping, detectors and data acquisition and processing. 

PMID- 27046343
TI  - Determinants of the pKa values of ionizable residues in an intrinsically
      disordered protein.
AB  - Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes; in humans,
      they are often associated with diseases. The protein NUPR1 is a multifunctional
      IDP involved in the development and progression of pancreatic cancer; therefore,
      it constitutes a target for drug design. In an effort to contribute to the
      understanding of the conformational features of NUPR1 and to provide clues on
      amino acid interactions in disordered states of proteins, we measured the pKa
      values of all its acidic groups (aspartic and glutamic residues, and backbone C
      terminus) by using NMR spectroscopy at low (100 mM) and high (500 mM) NaCl
      concentration. At low ionic strength, the pKa values were similar to those
      reported for random-coil models, except for Glu18 and Asp19, suggesting
      electrostatic interactions around these residues. Molecular modelling and
      simulation indicate an additional, significant role of nearby proline residues in
      determining the polypeptide conformational features and water accessibility in
      the region around Glu18, modulating the titration properties of these amino
      acids. In the other acidic residues of NUPR1, the small deviations of pKa values
      (compared to those expected for a random-coil) are likely due to electrostatic
      interactions with charged adjacent residues, which should be reduced at high NaCl
      concentrations. In fact, at high ionic strength, the pKa values of the aspartic
      residues were similar to those in a random coil, but there were still small
      differences for those of glutamic acids, probably due to hydrogen-bond formation.
      The overall findings suggest that local interactions and hydrophobic effects play
      a major role in determining the electrostatic features of NUPR1, whereas long
      range charge contributions appear to be of lesser importance.

PMID- 27046344
TI  - Factors predicting survival in amyotrophic lateral sclerosis patients on non
      invasive ventilation.
AB  - OBJECTIVE: Non invasive ventilation (NIV) improves quality of life and extends
      survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist
      about the factors related to survival. We intended to assess the predictive
      factors that influence survival in patients after NIV initiation. METHODS:
      Patients who started NIV from 2000 to 2014 and were tolerant (compliance >= 4
      hours) were included; demographic, disease related and respiratory variables at
      NIV initiation were analysed. Statistical analysis was performed using the Kaplan
      Meier test and Cox proportional hazard models. RESULTS: 213 patients were
      included with median survival from NIV initiation of 13.5 months. In univariate
      analysis, the identified risk factors for mortality were severity of bulbar
      involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR
      0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS
      R (HR 0.97) were independent predictive factors of survival in patients on NIV.
      CONCLUSIONS: In our study, the two prognostic factors in ALS patients following
      NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV
      initiation. A better assessment of bulbar involvement, including evaluation of
      the upper airway, and a careful titration on NIV are necessary to optimize
      treatment efficacy.

PMID- 27046345
TI  - A snail-eating snake recognizes prey handedness.
AB  - Specialized predator-prey interactions can be a driving force for their
      coevolution. Southeast Asian snail-eating snakes (Pareas) have more teeth on the
      right mandible and specialize in predation on the clockwise-coiled (dextral)
      majority in shelled snails by soft-body extraction. Snails have countered the
      snakes' dextral-predation by recurrent coil reversal, which generates diverse
      counterclockwise-coiled (sinistral) prey where Pareas snakes live. However,
      whether the snake predator in turn evolves any response to prey reversal is
      unknown. We show that Pareas carinatus living with abundant sinistrals avoids
      approaching or striking at a sinistral that is more difficult and costly to
      handle than a dextral. Whenever it strikes, however, the snake succeeds in
      predation by handling dextral and sinistral prey in reverse. In contrast, P.
      iwasakii with little access to sinistrals on small peripheral islands attempts
      and frequently misses capturing a given sinistral. Prey-handedness recognition
      should be advantageous for right-handed snail-eating snakes where frequently
      encountering sinistrals. Under dextral-predation by Pareas snakes, adaptive
      fixation of a prey population for a reversal gene instantaneously generates a
      sinistral species because interchiral mating is rarely possible. The novel
      warning, instead of sheltering, effect of sinistrality benefitting both predators
      and prey could further accelerate single-gene ecological speciation by left-right
      reversal. 

PMID- 27046346
TI  - Study of natural health product-drug adverse reactions (S.O.N.A.R.) in patients
      seeking mental health services.
AB  - BACKGROUND: Natural health products (N.H.P.s) are frequently used by mental
      health patients, who are also more likely to be given prescription medications.
      Few patients report use of N.H.P.s to their health care providers, increasing the
      challenges of safe N.H.P. use. OBJECTIVE: To determine: (1) the proportion of
      patients seeking mental health services taking prescription drugs only, N.H.P.s
      only, prescription drug-N.H.P.s concurrently and neither, (2) which prescription
      drugs and N.H.P.s are most commonly used by these patients, either alone or in
      combination, (3) what proportion of patients in each of the above groups report
      an adverse event (A.E.) using active surveillance, and (4) what type of A.E.s are
      reported in these patient groups. METHOD: Employing active surveillance,
      participating clinicians from six mental health clinics in Edmonton, Alberta
      asked individuals seeking mental health services about (i) prescription drug use,
      ii) N.H.P. use, and iii) experiences of A.E.s. RESULTS: Of 1466 patients with
      complete screening data available, 672 (45.8%) patients took prescription drugs
      only, 79 (5.4%) took N.H.P.s only, 279 (19.0%) took N.H.P.s and drugs
      concurrently and 436 (29.7%) took neither. In total, 147 patients reported an
      A.E., representing 10.7%, 2.5%, 25.5% and 0.5% of each population, respectively.
      Compared with prescription drug use, patients reporting concurrent N.H.P.-drug
      use were 2.8 times more likely to experience an A.E. (95% C.I.: 2.0-4.1; p <
      0.001). A key limitation of the study is the lack of causality assessment of
      A.E.s reported; additionally, the patient population reflects a population that
      phones a provincial mental health phone line with or without referral from a
      mental health professional. CONCLUSION: Nearly one-fifth of patients seeking
      mental health services take N.H.P.s and prescription drugs concurrently; these
      patients are also at a greater risk of experiencing an A.E. Active surveillance
      provides a valuable means of detecting such A.E.s and can be incorporated into
      the medical histories obtained by clinicians.

PMID- 27046347
TI  - Cost-effectiveness of stent-retriever thrombectomy in combination with IV t-PA
      compared with IV t-PA alone for acute ischemic stroke in the UK.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of neurothrombectomy with a stent
      retriever (Solitaire * Revascularization Device) in treating acute ischemic
      stroke patients from the UK healthcare provider perspective. METHODS: A Markov
      model was developed to simulate health outcomes and costs of two therapies over a
      lifetime time horizon: stent-retriever thrombectomy in combination with
      intravenous tissue-type plasminogen activator (IV t-PA), and IV t-PA alone. The
      model incorporated an acute phase (0-90 days) and a rest of life phase (90+
      days). Health states were defined by the modified Rankin Scale score. During the
      rest of life phase, patients remained in the same health state until a recurrent
      stroke or death. Clinical effectiveness and safety data were taken from the SWIFT
      PRIME study. Resource use and health state utilities were informed by published
      data. RESULTS: Combined stent-retriever thrombectomy and IV t-PA led to improved
      quality-of-life and increased life expectancy compared to IV t-PA alone. The
      higher treatment costs associated with the use of stent-retriever thrombectomy
      were offset by long-term cost savings due to improved patient health status,
      leading to overall cost savings of L33 190 per patient and a net benefit of L79
      402. Deterministic and probabilistic sensitivity analyses demonstrated that the
      results were robust to a wide range of parameter inputs. LIMITATIONS: The acute
      and long-term costs resource use data were taken from a study based on a patient
      population that was older and may have had additional comorbidities than the
      SWIFT PRIME population, resulting in costs that may not be representative of the
      cohort within this model. In addition, the estimates may not reflect stroke care
      today as no current evidence is available; however, the cost estimates were
      deemed reasonable by clinical opinion. CONCLUSIONS: Combined stent-retriever
      neurothrombectomy and IV t-PA is a cost-effective treatment for acute ischemic
      stroke compared with IV t-PA alone.

PMID- 27046348
TI  - Dinaphthozethrene and Diindenozethrene: Synthesis, Structural Analysis, and
      Properties.
AB  - Zethrene-based condensed arenes dinaphthozethrene and diindenozethrene were
      synthesized by oxidative cyclodehydrogenation and palladium-catalyzed cyclization
      of 7,14-diarylzethrenes, respectively. Their structures were analyzed by X-ray
      crystallography. The photophysical and electrochemical properties of these
      compounds were investigated. 

PMID- 27046349
TI  - Ethnic Identity as a Predictor of Microaggressions Toward Blacks, Whites, and
      Hispanic LGBs by Blacks, Whites, and Hispanics.
AB  - Results of the study suggest racial differences still exist when it comes to
      attitudes toward homosexuality in the United States. Findings indicate Black
      individuals hold significantly less favorable attitudes toward
      lesbian/gay/bisexual (LGB) individuals than non-Hispanic White individuals but
      not Hispanics, after controlling for demographics. Hispanic individuals'
      attitudes toward LGBs were not significantly different from those of non-Hispanic
      Whites. Despite less favorable attitudes toward LGBs, however, Black Americans
      display a significantly lower likelihood of engaging in LGB-directed
      microaggressions than both non-Hispanic Whites and Hispanics. Finally, the
      results of the study indicate that as non-Hispanic White individuals' ethnic
      identity gets stronger, their likelihood of engaging in microaggressions toward
      LGBs increases, more so than Black or Hispanic individuals.

PMID- 27046350
TI  - Improving the High-Voltage Li2FeMn3O8 Cathode by Chlorine Doping.
AB  - High-capacity and high-voltage cathode materials are desirable for high-energy
      density lithium ion batteries. Among various cathode materials, Li2FeMn3O8 is
      attractive due to its high working voltage, low toxicity, and low cost. However,
      its superior electrochemical properties are significantly limited by the
      intrinsic defects in the Li2FeMn3O8 cathode, which makes the theoretical working
      voltage (4.9 V) and capacity (148 mAh/g) hard to reach. In this paper, we
      demonstrated that Cl doping can effectively increase the capacity and working
      voltage of the Li2FeMn3O8 cathode. X-ray photoelectron spectroscopy reveals that
      Cl doping reduced the valence state and increased the electron binding energy in
      cations and thus increased the voltage and enhanced the capacity of the
      Li2FeMn3O8 cathode. Our results also indicate that Cl doping can be a promising
      low-cost method to improve the electrochemical performance of various oxide
      cathode materials, including LiCoO2 and LiMn2O4.

PMID- 27046351
TI  - Should Immunosuppressive Therapy Be Used in Slowly Progressive IgA Nephropathy?

PMID- 27046354
TI  - Into Bondage: Aaron Douglas.

PMID- 27046362
TI  - A PIECE OF MY MIND. Say What You Mean, Mean What You Say.

PMID- 27046363
TI  - Screening, Case-Finding, and Outcomes for Adults With Unrecognized COPD.

PMID- 27046364
TI  - Change in Pain and Physical Function Following Bariatric Surgery for Severe
      Obesity.
AB  - IMPORTANCE: The variability and durability of improvements in pain and physical
      function following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable
      gastric banding (LAGB) are not well described. OBJECTIVES: To report changes in
      pain and physical function in the first 3 years following bariatric surgery, and
      to identify factors associated with improvement. DESIGN, SETTING, AND
      PARTICIPANTS: The Longitudinal Assessment of Bariatric Surgery-2 is an
      observational cohort study at 10 US hospitals. Adults with severe obesity
      undergoing bariatric surgery were recruited between February 2005 and February
      2009. Research assessments were conducted prior to surgery and annually
      thereafter. Three-year follow-up through October 2012 is reported. EXPOSURES:
      Bariatric surgery as clinical care. MAIN OUTCOMES AND MEASURES: Primary outcomes
      were clinically meaningful presurgery to postsurgery improvements in pain and
      function using scores from the Medical Outcomes Study 36-Item Short-Form Health
      Survey (SF-36) (ie, improvement of >=5 points on the norm-based score [range, 0
      100]) and 400-meter walk time (ie, improvement of >=24 seconds) using established
      thresholds. The secondary outcome was clinically meaningful improvement using the
      Western Ontario McMaster Osteoarthritis Index (ie, improvement of >=9.7 pain
      points and >=9.3 function points on the transformed score [range, 0-100]).
      RESULTS: Of 2458 participants, 2221 completed baseline and follow-up assessments
      (1743 [78.5%] were women; median age was 47 years; median body mass index [BMI]
      was 45.9; 70.4% underwent RYGB; 25.0% underwent LAGB). At year 1, clinically
      meaningful improvements were shown in 57.6% (95% CI, 55.3%-59.9%) of participants
      for bodily pain, 76.5% (95% CI, 74.6%-78.5%) for physical function, and 59.5%
      (95% CI, 56.4%-62.7%) for walk time. Additionally, among participants with severe
      knee or disability (633), or hip pain or disability (500) at baseline,
      approximately three-fourths experienced joint-specific improvements in knee pain
      (77.1% [95% CI, 73.5%-80.7%]) and in hip function (79.2% [95% CI, 75.3%-83.1%]).
      Between year 1 and year 3, rates of improvement significantly decreased to 48.6%
      (95% CI, 46.0%-51.1%) for bodily pain and to 70.2% (95% CI, 67.8%-72.5%) for
      physical function, but improvement rates for walk time, knee and hip pain, and
      knee and hip function did not (P for all >=.05). Younger age, male sex, higher
      income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no
      venous edema with ulcerations postsurgery (either no history or remission); and
      presurgery-to-postsurgery reductions in weight and depressive symptoms were
      associated with presurgery-to-postsurgery improvements in multiple outcomes at
      years 1, 2, and 3. CONCLUSIONS AND RELEVANCE: Among a cohort of participants with
      severe obesity undergoing bariatric surgery, a large percentage experienced
      improvement, compared with baseline, in pain, physical function, and walk time
      over 3 years, but the percentage with improvement in pain and physical function
      decreased between year 1 and year 3. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00465829.

PMID- 27046365
TI  - Screening for Chronic Obstructive Pulmonary Disease: US Preventive Services Task
      Force Recommendation Statement.
AB  - IMPORTANCE: About 14% of US adults aged 40 to 79 years have chronic obstructive
      pulmonary disease (COPD), and it is the third leading cause of death in the
      United States. Persons with severe COPD are often unable to participate in normal
      physical activity due to deterioration of lung function. OBJECTIVE: To update the
      2008 US Preventive Services Task Force (USPSTF) recommendation on screening for
      COPD in asymptomatic adults. EVIDENCE REVIEW: The USPSTF reviewed the evidence on
      whether screening for COPD in asymptomatic adults (those who do not recognize or
      report respiratory symptoms) improves health outcomes. The USPSTF reviewed the
      diagnostic accuracy of screening tools (including prescreening questionnaires and
      spirometry); whether screening for COPD improves the delivery and uptake of
      targeted preventive services, such as smoking cessation or relevant
      immunizations; and the possible harms of screening for and treatment of mild to
      moderate COPD. FINDINGS: Similar to 2008, the USPSTF did not find evidence that
      screening for COPD in asymptomatic persons improves health-related quality of
      life, morbidity, or mortality. The USPSTF determined that early detection of
      COPD, before the development of symptoms, does not alter the course of the
      disease or improve patient outcomes. The USPSTF concludes with moderate certainty
      that screening for COPD in asymptomatic persons has no net benefit. CONCLUSIONS
      AND RECOMMENDATION: The USPSTF recommends against screening for COPD in
      asymptomatic adults. (D recommendation).

PMID- 27046366
TI  - Screening for Chronic Obstructive Pulmonary Disease: Evidence Report and
      Systematic Review for the US Preventive Services Task Force.
AB  - IMPORTANCE: Chronic obstructive pulmonary disease (COPD) is the third leading
      cause of death in the United States. OBJECTIVE: To systematically review
      literature on the accuracy of screening questionnaires and office-based screening
      pulmonary function testing and the efficacy and harms of treatment of screen
      detected COPD. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register
      of Controlled Trials for relevant English-language studies published through
      January 2015. STUDY SELECTION: Two reviewers independently screened abstracts and
      studies. The search yielded 13,141 unique citations; 465 full-text articles were
      reviewed, and 33 studies met the inclusion criteria. DATA EXTRACTION AND
      SYNTHESIS: Two reviewers rated the quality of each study using USPSTF criteria.
      MAIN OUTCOMES AND MEASURES: Diagnostic accuracy (sensitivity, specificity,
      positive predictive value [PPV], and negative predictive value [NPV]; treatment
      efficacy (COPD exacerbations, all-cause mortality, quality of life, and dyspnea);
      and treatment harms. RESULTS: All screening questionnaires were based on symptoms
      as well as risk factors such as age and smoking history. The COPD Diagnostic
      Questionnaire was the most extensively studied (5 studies, n = 3048), with
      moderate overall performance for COPD detection: area under the receiver
      operating characteristic curve (AUC), 0.65 to 0.72; sensitivity, 80% to 93%; and
      specificity, 24% to 49%, at a threshold of greater than 16.5. Positive predictive
      value and NPV ranged from 17% to 45% and 76% to 98%, respectively. For pulmonary
      function-based screening tools, FEV1/FEV6 was the best studied (3 studies, n =
      1587), with AUC ranging from 0.84 to 0.85. Sensitivity ranged from 51% to 80%.
      Specificity (range, 90%-95%) and PPV (range, 63%-75%) appeared better than
      questionnaires. There was not strong evidence to support that screening and
      supplying smokers with spirometry results improves smoking cessation rates.
      Treatment trials were unavailable for screen-detected patients. Trials that
      reported outcomes in patients with mild to moderate COPD included 2 trials of
      long-acting beta-agonists (LABAs) (n = 3174), 1 RCT of LABAs and inhaled
      corticosteroids (ICS) (n = 1097), 5 RCTs of the long-acting muscarinic antagonist
      tiotropium (n = 4592), and 6 RCTs of ICS (n = 3983). They suggested no benefit in
      all-cause mortality, but a decrease in annual rates of exacerbations with
      pharmacologic treatments. Few trials reported harms for any individual drug
      class. Adverse effects were generally mild (eg, dry mouth and cough). CONCLUSIONS
      AND RELEVANCE: There was no direct evidence available to determine the benefits
      and harms of screening asymptomatic adults for COPD using questionnaires or
      office-based screening pulmonary function testing or to determine the benefits of
      treatment in screen-detected populations. Indirect evidence suggests that the
      COPD Diagnostic Questionnaire has moderate overall performance for COPD
      detection. Among patients with mild to moderate COPD, the benefit of
      pharmacotherapy for reducing exacerbations was modest.

PMID- 27046367
TI  - Actinic Keratosis.

PMID- 27046368
TI  - Postprocedural Blue Toes.

PMID- 27046369
TI  - Expenditures and Prices of Antihyperglycemic Medications in the United States:
      2002-2013.

PMID- 27046370
TI  - Breast Cancer Screening: Benefit or Harm?

PMID- 27046371
TI  - Breast Cancer Screening: Benefit or Harm?--Reply.

PMID- 27046372
TI  - Clinical Breast Examination and Breast Cancer Screening Guideline.

PMID- 27046373
TI  - Screening Mammography and Age Recommendations.

PMID- 27046374
TI  - Clinical Breast Examination and Breast Cancer Screening Guideline--Reply.

PMID- 27046375
TI  - Screening Mammography and Age Recommendations--Reply.

PMID- 27046376
TI  - Typographical Error and Added Reference.

PMID- 27046377
TI  - Unclear Information in Table.

PMID- 27046378
TI  - Incorrect Data in 2 Tables.

PMID- 27046380
TI  - E Pluribus Unum Forever.

PMID- 27046381
TI  - Compulsory Health Insurance.

PMID- 27046382
TI  - JAMA PATIENT PAGE. Screening for Chronic Obstructive Pulmonary Disease.

PMID- 27046383
TI  - Effect of pH on elemental sulfur conversion and microbial communities by
      autotrophic simultaneous desulfurization and denitrification.
AB  - pH has an important influence on the elemental sulfur accumulated in an
      autotrophic simultaneous desulfurization and denitrification process. The
      influent nitrate to sulfide (N/S) mole ratio was set to 0.5, 0.67, 1.0, 1.33 and
      2.0 with a 200 mg/L sulfide concentration. The effect of pH on elemental sulfur
      conversion and microbial communities was studied. Sulfide removal was achieved to
      the extent of 98% under near-neutral and weak base conditions after 24 h of
      reaction. The conversion rate of elemental sulfur was 29.41% under the near
      neutral condition. The weak base condition led to greater formation of sulfate,
      and the nitrate used by the microorganisms was transformed mainly to N2 with a
      removal rate of 96%. Increasing the retention time from 24 to 48 h caused the
      removal rate of nitrate increased from 63.58% to 90% under the near-neutral
      condition. Sulfurovum sp. was the functioning bacterial species, and bands 1 and
      2 represent different species of Sulfurovum sp. in the system according to the
      PCR-DGGE analysis of the microbial community structure. The functional bacteria
      represented by band 1 produced mainly sulfate, but the functional bacteria
      represented by band 2 produced mainly elemental sulfur. 

PMID- 27046387
TI  - Effects of Blended Cardiopulmonary Resuscitation and Defibrillation E-learning on
      Nursing Students' Self-efficacy, Problem Solving, and Psychomotor Skills.
AB  - This study was conducted to identify the educational effects of a blended e
      learning program for graduating nursing students on self-efficacy, problem
      solving, and psychomotor skills for core basic nursing skills. A one-group
      pretest/posttest quasi-experimental design was used with 79 nursing students in
      Korea. The subjects took a conventional 2-week lecture-based practical course,
      together with spending an average of 60 minutes at least twice a week during 2
      weeks on the self-guided e-learning content for basic cardiopulmonary
      resuscitation and defibrillation using Mosby's Nursing Skills database. Self- and
      examiner-reported data were collected between September and November 2014 and
      analyzed using descriptive statistics, paired t test, and Pearson correlation.
      The results showed that subjects who received blended e-learning education had
      improved problem-solving abilities (t = 2.654) and self-efficacy for nursing
      practice related to cardiopulmonary resuscitation and defibrillation (t = 3.426).
      There was also an 80% to 90% rate of excellent postintervention performance for
      the majority of psychomotor skills, but the location of chest compressions,
      compression rate per minute, artificial respiration, and verification of patient
      outcome still showed low levels of performance. In conclusion, blended E
      learning, which allows self-directed repetitive learning, may be more effective
      in enhancing nursing competencies than conventional practice education. 

PMID- 27046388
TI  - Operating Room Delays: Meaningful Use in Electronic Health Record.
AB  - Perioperative areas are the most costly to operate and account for more than 40%
      of expenses. The high costs prompted one organization to analyze surgical delays
      through a retrospective review of their new electronic health record. Electronic
      health records have made it easier to access and aggregate clinical data; 2123
      operating room cases were analyzed. Implementing a new electronic health record
      system is complex; inaccurate data and poor implementation can introduce new
      problems. Validating the electronic health record development processes
      determines the ease of use and the user interface, specifically related to user
      compliance with the intent of the electronic health record development. The
      revalidation process after implementation determines if the intent of the design
      was fulfilled and data can be meaningfully used. In this organization, the data
      fields completed through automation provided quantifiable, meaningful data.
      However, data fields completed by staff that required subjective decision making
      resulted in incomplete data nearly 24% of the time. The ease of use was further
      complicated by 490 permutations (combinations of delay types and reasons) that
      were built into the electronic health record. Operating room delay themes emerged
      notwithstanding the significant complexity of the electronic health record build;
      however, improved accuracy could improve meaningful data collection and a more
      accurate root cause analysis of operating room delays. Accurate and meaningful
      use of data affords a more reliable approach in quality, safety, and cost
      effective initiatives. 

PMID- 27046389
TI  - Copper induced apoptosis in Caco-2 and Hep-G2 cells: Expression of caspases 3, 8
      and 9, AIF and p53.
AB  - Copper (Cu) is an essential trace metal needed to ensure cell function. However,
      when present at high concentrations it becomes toxic to organisms. Cell death,
      induced by toxic levels of copper, was previously observed in in vitro studies.
      However, there is no consensus about the cell death pathway induced by Cu and it
      is still not known whether this occurs as a result of the direct action of the
      metal or by indirect effects. In the present work, we intend to identify the
      influence of different Cu concentrations in the induction of apoptosis and to
      explore the potential signaling pathways, using two different in vitro cell
      culture models (Caco-2 and Hep-G2). Cells were exposed, during 6, 12, 24 and 48h,
      to Cu concentrations corresponding to IC50 and 1/8 of IC50, according to the
      viability assays. Then, considering the different apoptosis pathways, the
      expression of caspases 3, 8 and 9, apoptosis inducing factor (AIF) and p53 genes
      was analyzed by quantitative real time PCR. The results suggested that different
      Cu concentrations could trigger different apoptotic pathways, at different times
      of exposure. In both cell lines, apoptosis seems to be initiated by caspase
      independent pathway and intrinsic pathway, followed by extrinsic pathway. In
      conclusion, this study demonstrates that Cu induces the activation of apoptosis
      through caspase dependent and independent pathways, also suggesting that
      apoptosis activation mechanism is dependent on the concentration, time of
      exposure to Cu and cell type. 

PMID- 27046391
TI  - Long-Term Effect of Anti-VEGF Agents on Intraocular Pressure in Age-Related
      Macular Degeneration.
AB  - PURPOSE: To analyze the effect of anti-vascular endothelial growth factor (VEGF)
      agents on intraocular pressure (IOP) in patients with neovascular age-related
      macular degeneration (AMD). Materials andMethods: This is a retrospective study
      that included 72 patients treated unilaterally with anti-VEGF agents according to
      a pro re nata regimen. Fellow noninjected eyes (n = 72) were used as controls.
      IOP variation and the development of sustained ocular hypertension (OHT) were
      assessed both in the injected and in the fellow eyes. RESULTS: While the final
      IOP was not significantly different between the 2 groups, sustained OHT developed
      in 4.2% of the injected eyes and 1.4% of the controls. In the study group, no
      significant IOP variation was noted during follow-up in patients receiving <=20
      injections, but there was a significant increase in IOP with time in more
      frequently treated patients (p = 0.041). Comparison of both subgroups
      demonstrated that patients receiving >20 injections suffered significantly
      greater IOP variation (p = 0.034) during follow-up, and that these patients
      tended to require IOP-lowering treatment more frequently (p = 0.090). CONCLUSION:
      Multiple anti-VEGF injections lead to an increase in IOP, although this variation
      is not sufficient to cause development of OHT in the majority of patients.

PMID- 27046390
TI  - Acute skin toxicity associated with a 1-week schedule of whole breast
      radiotherapy compared with a standard 3-week regimen delivered in the UK FAST
      Forward Trial.
AB  - BACKGROUND AND PURPOSE: FAST-Forward is a phase 3 clinical trial testing a 1-week
      course of whole breast radiotherapy against the UK standard 3-week regimen after
      primary surgery for early breast cancer. Two acute skin toxicity substudies were
      undertaken to test the safety of the test schedules with respect to early skin
      reactions. MATERIAL AND METHODS: Patients were randomly allocated to 40Gy/15
      fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin
      reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03
      (second substudy) weekly during treatment and for 4weeks after treatment ended.
      Primary endpoint was the proportion of patients within each treatment group with
      grade ?3 toxicity (RTOG and CTCAE, respectively) at any time from the start of
      radiotherapy to 4weeks after completion. RESULTS: 190 and 162 patients were
      recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity
      were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the
      second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F
      0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53. CONCLUSIONS: Acute breast skin reactions
      with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward
      were mild.

PMID- 27046392
TI  - Toward validation of a borderline personality disorder-relevant picture set.
AB  - This investigation sought to validate a stimulus set previously adapted by expert
      consensus from the International Affective Picture System to be unpleasant and
      evocative to individuals with borderline personality disorder (BPD). This set was
      rated as significantly more arousing by 22 individuals diagnosed with BPD
      compared to 22 healthy controls, though this mean difference appeared to be
      driven by differences in ratings for a small subset of pictures. The present BPD
      sample did not rate the BPD-specific picture set as more arousing than a previous
      BPD sample (Herpertz, Kunert, Schwenger, & Sass, 1999) had rated a different set
      of unpleasant, but non-BPD-specific International Affective Picture System
      images. Future BPD-specific image sets may benefit from including images that
      more closely target BPD sensitivities and features. (PsycINFO Database Record

PMID- 27046393
TI  - Schizotypy and specificity of negative emotions on an emotional Stroop paradigm
      in the general population.
AB  - Attentional-interference using emotional Stroop tasks (ESTs) is greater among
      individuals in the general population with positive (versus negative) schizotypal
      traits; specifically in response to negatively (versus positively) valenced
      words, potentially capturing threat-sensitivity. Variability in attentional
      interference as a function of subcategories of negatively valenced words (and in
      relation to schizotypal traits) remains underexplored in EST studies. We examined
      attentional-interference across negative word subcategories
      (fear/anger/sadness/disgust), and in relation to positive schizotypy, among non
      clinical individuals in the general population reporting varying degrees of
      schizotypal traits. As hypothesized, performance differed across word
      subcategories, though the pattern varied from expectation. Attentional
      interference was greater for fear and sadness compared to anger; and analogous
      for fear, disgust, and sadness. In the high schizotypy group, positive
      schizotypal traits were directly associated with attentional-interference to
      disgust. Attentional-interference was comparable between high- and low-positive
      schizotypy. Results suggest negative emotion subcategories may differentially
      reflect threat-sensitivity. Disgust-sensitivity may be particularly salient in
      (non-clinical) positive schizotypy. Findings have implications for understanding
      negative emotion specificity and variability in stimulus presentation modality
      when studying threat-related attentional-interference. Finally, disgust-related
      attentional-interference may serve as a cognitive correlate of (non-clinical)
      positive schizotypy. Expanding this research to prodromal populations will help
      explore disgust-related attentional-interference as a potential cognitive marker
      of positive symptoms.

PMID- 27046394
TI  - Psychosocial functioning, quality of life and clinical correlates of comorbid
      alcohol and drug dependence syndromes in people with schizophrenia across Europe.
AB  - Little is known about the correlates of comorbid drug and alcohol dependence in
      people with schizophrenia outside the USA. We tested hypotheses that dependence
      on alcohol/drugs would be associated with more severe symptoms, and poorer
      psychosocial functioning and quality of life. The EuroSC Cohort study (N=1204),
      based in France, Germany and the UK, used semi-structured clinical interviews for
      diagnoses, and standardized tools to assess correlates. We used mixed models to
      compare outcomes between past-year comorbid dependence on alcohol/drugs,
      controlling for covariates and modelling both subject and country-level effects.
      Participants dependent on alcohol or drugs had fewer negative symptoms on PANSS
      than their non-dependent counterparts. However, those dependent on alcohol scored
      higher on PANSS general psychopathology than those who were not, or dependent
      only on drugs. People with schizophrenia dependent on drugs had poorer quality of
      life, more extrapyramidal side effects, and scored worse on Global Assessment of
      Functioning (GAF) than those without dependence. People with alcohol dependence
      reported more reasons for non-compliance with medication, and poorer functioning
      on GAF, though not on Global Assessment of Relational Functioning. In people with
      schizophrenia, comorbid dependence on alcohol or drugs is associated with
      impaired clinical and psychosocial adjustment, and poorer quality of life.

PMID- 27046395
TI  - Observation of the Zero Doppler Effect.
AB  - The normal Doppler effect has well-established applications in many areas of
      science and technology. Recently, a few experimental demonstrations of the
      inverse Doppler effect have begun to appear in negative-index metamaterials. Here
      we report an experimental observation of the zero Doppler effect, that is, no
      frequency shift irrespective of the relative motion between the wave signal
      source and the detector in a zero-index metamaterial. This unique phenomenon,
      accompanied by the normal and inverse Doppler effects, is generated by reflecting
      a wave from a moving discontinuity in a composite right/left-handed transmission
      line loaded with varactors when operating in the near zero-index passband, or the
      right/left-handed passband. This work has revealed a complete picture of the
      Doppler effect in metamaterials and may lead to potential applications in
      electromagnetic wave related metrology. 

PMID- 27046396
TI  - Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and
      Attenuates Cognitive Impairments in Mice.
AB  - Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of
      cancer. In this study, we found for the first time that sunitinib inhibits
      acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In
      addition, sunitinib dramatically decreased the hippocampal and cortical activity
      of AChE in a time-dependent manner in mice. Molecular docking analysis further
      demonstrates that sunitinib might interact with both the catalytic anion and
      peripheral anionic sites within AChE, which is in accordance with enzymatic
      activity results showing that sunitinib inhibits AChE in a mixed pattern. Most
      importantly, we evaluated the effects of sunitinib on scopolamine-induced
      cognitive impairments in mice by using novel object recognition and Morris water
      maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a
      similar extent as donepezil, a marketed AChE inhibitor used for the treatment of
      Alzheimer's disease. In summary, our results have shown that sunitinib could
      potently inhibit AChE and attenuate cognitive impairments in mice.

PMID- 27046397
TI  - Anti-methicillin resistant Staphylococcus aureus activity, synergism with
      oxacillin and molecular docking studies of metronidazole-triazole hybrids.
AB  - MRSA causes 60-70% of Staphylococcus aureus infection in hospitals and it has
      developed resistance against the currently available drugs. Interestingly, a
      series of 35 metronidazole-triazole hybrids on screening against MRSA were found
      to be active. Compound 22 was found to be effective at 4 MUg/mL concentration
      against nine strains of MRSA. The inhibitory activity was further enhanced upto 1
      MUg/mL when this compound was used in combination with oxacillin in 1:1 ratio.
      All the compounds were found to be non-toxic in THP-1 cell line upto a
      concentration of 50 MUM. The time-kill kinetics studies suggested bacteriostatic
      nature of the compounds. In silico studies show that these compounds interact
      with Thr600, Ser598, Asn464, His583 and Tyr446 in the active site of PBP2a
      crystal structure from MRSA. 

PMID- 27046398
TI  - Comparing Electronic and Manual Tracking Systems for Monitoring Resident Duty
      Hours.
AB  - BACKGROUND: Changes in the Accreditation Council for Graduate Medical Education
      (ACGME) duty hour requirements have created significant monitoring
      responsibilities for institutions. This study explored the types of tracking
      systems used and determined for each type of tracking system the number of
      violations identified and the number of ACGME citations issued. METHODS: An 8
      question, anonymous, electronic survey was sent to 3,275 residency program
      coordinators across 24 ACGME-accredited specialties nationwide. The survey was
      developed by the study investigators to gather data on the type of system used by
      programs, perceived advantages and disadvantages of the system, the number and
      types of violations identified, and subsequent ACGME citations for duty hour
      noncompliance. RESULTS: Of the 889 responses (27.1% response rate), 780 (87.7%)
      reported using an electronic system, while 94 (10.6%) used a manual system.
      Programs found electronic systems significantly superior on most characteristics,
      including accuracy, effectiveness, ease of use, reliability, reporting variety,
      and time investment (all P<0.001). Electronic systems identified significantly
      more violations than their manual counterparts; however, violation identification
      did not correlate with an increase in ACGME duty hour citations for programs
      using electronic systems (all P>0.05). CONCLUSION: Although a relationship was
      seen between the tracking system and the number of violations identified, no
      significant relationship was detected between the system used and the number of
      citations issued by the ACGME. While programs have invested considerable time,
      effort, and expense in systems to track duty hours, the real meaning of the data
      collected and its value to programs, residents, the ACGME, and the healthcare
      system remains unclear.

PMID- 27046399
TI  - Medical Graduates, Tertiary Hospitals, and Burnout: A Longitudinal Cohort Study.
AB  - BACKGROUND: Burnout among junior doctors can affect patient care. We conducted a
      longitudinal cohort study designed to explore the incidence of burnout in medical
      interns and to examine the changes in burnout during the course of the intern
      year. METHODS: Interns were recruited at two tertiary hospitals in Brisbane,
      Australia (n=180). Participants completed surveys at four time points during
      their internship year. All interns (100%) completed the baseline survey during
      their orientation. Response rates were 85%, 88%, and 79%, respectively, at 5
      week, 6-month, and 12-month follow-up. RESULTS: Interns reported high levels of
      personal and work-related burnout throughout the year that peaked at 6 months
      with mean scores of 42.53 and 41.81, respectively. Increases of 5.1 points
      (confidence interval [CI] 2.5,7.7; P=0.0001) and 3.5 points (CI 1.3,5.6;
      P=0.0015) were seen at 6 months for personal and work-related burnout,
      respectively. The mean score for patient-related burnout at 12 months was 25.57,
      and this number had increased significantly by 5.8 points (CI 3.2,8.5; P<0.0001)
      throughout the year. Correlation with demographic variables (age, sex) were
      found. The total incidence of burnout was 55.9%. CONCLUSION: Our study showed
      that burnout is a common problem among interns. The high incidence of burnout
      demonstrates the need for appropriate strategies to prevent adverse effects on
      doctors' quality of life and on the quality of care patients receive.

PMID- 27046400
TI  - Initial Match Rates of an Innovative International Partnership: The Ochsner
      Clinical School Experience.
AB  - BACKGROUND: Ochsner Clinical School (OCS) is a unique partnership between Ochsner
      Health System in New Orleans, LA, and The University of Queensland (UQ) School of
      Medicine in Brisbane, Australia. OCS trains physicians in global medicine and
      promotes careers in primary care through its unique structure. The purpose of
      this study was to determine how OCS graduates perform in the National Resident
      Matching Program (NRMP)-The Match-compared to applicants from other types of
      medical schools. METHODS: The match outcomes for all OCS graduates since the
      first graduating class in November 2012 were compared to the match outcomes in
      the NRMP database for graduates from other types of medical schools in the years
      2013-2015. We also examined the number of OCS students electing residencies in
      primary care compared to the number of US medical school graduates overall during
      the same time period of 2013-2015. RESULTS: The cumulative match rate from 2013
      2015 for applicants from OCS was 91.8%. The OCS graduates' match rate was greater
      than the match rate for US citizen graduates of international medical schools
      during the same period (53.0% vs 91.8% [z=6.066, P<0.0002]), greater than the
      match rate for applicants from US osteopathic medical schools (77.3% vs 91.8%
      [z=25.233, P<0.0002]), and greater than the match rate for applicants from
      Canadian medical schools (62.7% vs 91.8% [z=3.815, P<0.0002]). The OCS match rate
      was not significantly different from that of US medical school graduates: 94.0%
      vs 91.8% (z=-0.728, P=0.4666). During the 2013-2015 time frame, 44.3% of OCS
      graduates chose residencies in primary care fields compared to 38.3% of US
      graduates (z=-0.9634, P=0.337). CONCLUSION: Graduates of OCS are obtaining
      residency positions through The Match at rates comparable to those of US medical
      school graduates and at rates significantly greater than other groups, and we are
      seeing a trend in the number of graduates choosing careers in primary care.

PMID- 27046401
TI  - Using the Flipped Classroom to Bridge the Gap to Generation Y.
AB  - BACKGROUND: The flipped classroom is a student-centered approach to learning that
      increases active learning for the student compared to traditional classroom-based
      instruction. In the flipped classroom model, students are first exposed to the
      learning material through didactics outside of the classroom, usually in the form
      of written material, voice-over lectures, or videos. During the formal teaching
      time, an instructor facilitates student-driven discussion of the material via
      case scenarios, allowing for complex problem solving, peer interaction, and a
      deep understanding of the concepts. A successful flipped classroom should have
      three goals: (1) allow the students to become critical thinkers, (2) fully engage
      students and instructors, and (3) stimulate the development of a deep
      understanding of the material. The flipped classroom model includes teaching and
      learning methods that can appeal to all four generations in the academic
      environment. METHODS: During the 2015 academic year, we implemented the flipped
      classroom in the obstetrics and gynecology clerkship for the Ochsner Clinical
      School in New Orleans, LA. Voice-over presentations of the lectures that had been
      given to students in prior years were recorded and made available to the students
      through an online classroom. Weekly problem-based learning sessions matched to
      the subjects of the traditional lectures were held, and the faculty who had
      previously presented the information in the traditional lecture format
      facilitated the problem-based learning sessions. The knowledge base of students
      was evaluated at the end of the rotation via a multiple-choice question
      examination and the Objective Structured Clinical Examination (OSCE) as had been
      done in previous years. We compared demographic information and examination
      scores for traditional teaching and flipped classroom groups of students. The
      traditional teaching group consisted of students from Rotation 2 and Rotation 3
      of the 2014 academic year who received traditional classroom-based instruction.
      The flipped classroom group consisted of students from Rotation 2 and Rotation 3
      of the 2015 academic year who received formal didactics via voice-over
      presentation and had the weekly problem-based learning sessions. RESULTS: When
      comparing the students taught by traditional methods to those taught in the
      flipped classroom model, we saw a statistically significant increase in test
      scores on the multiple-choice question examination in both the obstetrics and
      gynecology sections in Rotation 2. While the average score for the flipped
      classroom group increased in Rotation 3 on the obstetrics section of the multiple
      choice question examination, the difference was not statistically significant.
      Unexpectedly, the average score on the gynecology portion of the multiple-choice
      question examination decreased among the flipped classroom group compared to the
      traditional teaching group, and this decrease was statistically significant. For
      both the obstetrics and the gynecology portions of the OSCE, we saw statistically
      significant increases in the scores for the flipped classroom group in both
      Rotation 2 and Rotation 3 compared to the traditional teaching group. With the
      exception of the gynecology portion of the multiple-choice question examination
      in Rotation 3, we saw improvement in scores after the implementation of the
      flipped classroom. CONCLUSION: The flipped classroom is a feasible and useful
      alternative to the traditional classroom. It is a method that embraces Generation
      Y's need for active learning in a group setting while maintaining a traditional
      classroom method for introducing the information. Active learning increases
      student engagement and can lead to improved retention of material as demonstrated
      on standard examinations.

PMID- 27046402
TI  - Cancer Screening Rates in a Student-Run Free Clinic.
AB  - BACKGROUND: In the United States and in New York State, individuals with no
      health insurance have consistently lower screening rates for breast and cervical
      cancer than those with health insurance and are also more likely to be diagnosed
      with advanced stages of cancer. Our objective was to compare the cancer screening
      rates among patients at a free student-run clinic to state and national data. To
      our knowledge, ours is the first study examining breast and cervical screening
      rates and their relation to insurance status, income level, education level,
      race, and marital status in a suburban free student-run clinic. METHODS: As part
      of their intake from fall 2012 to spring 2013, patients at the Stony Brook Health
      Outreach and Medical Education Clinic in Stony Brook, NY, filled out a 26-item
      survey that included questions about race, income, education level, marital
      status, and cancer screening status. We compared the screening rates reported by
      our patients to published state and national rates. RESULTS: Breast and cervical
      cancer screening rates reported by 165 patients treated at our free student-run
      clinic were lower than the overall state and national averages. No significant
      associations between race, income, education level, or marital status and cancer
      screening rates were detected. CONCLUSION: Cancer screening rates at our free
      student-run clinic for the uninsured were lower than the overall state and
      national rates. These findings are consistent with previous reports of lower
      cancer preventive care utilization among the uninsured and suggest that insurance
      status has been a significant barrier to obtaining cancer screenings among our
      clinic population. Increasing cancer screening rates at student-run clinics may
      be a cost-effective secondary prevention activity that can decrease cancer
      mortality.

PMID- 27046403
TI  - Who's in Our Neighborhood? Healthcare Disparities Experiential Education for
      Residents.
AB  - BACKGROUND: Residents and fellows frequently care for patients from diverse
      populations but often have limited familiarity with the cultural preferences and
      social determinants that contribute to the health of their patients and
      communities. Faculty physicians at academic health centers are increasingly
      interested in incorporating the topics of cultural diversity and healthcare
      disparities into experiential education activities; however, examples have not
      been readily available. In this report, we describe a variety of experiential
      education models that were developed to improve resident and fellow physician
      understanding of cultural diversity and healthcare disparities. METHODS:
      Experiential education, an educational philosophy that infuses direct experience
      with the learning environment and content, is an effective adult learning method.
      This report summarizes the experiences of multiple sponsors of Accreditation
      Council for Graduate Medical Education-accredited residency and fellowship
      programs that used experiential education to inform residents about cultural
      diversity and healthcare disparities. The 9 innovative experiential education
      activities described were selected to demonstrate a wide range of complexity,
      resource requirements, and community engagement and to stimulate further
      creativity and innovation in educational design. RESULTS: Each of the 9 models is
      characterized by residents' active participation and varies in length from
      minutes to months. In general, the communities in which these models were
      deployed were urban centers with diverse populations. Various formats were used
      to introduce targeted learners to the populations and communities they serve.
      Measures of educational and clinical outcomes for these early innovations and
      pilot programs are not available. CONCLUSION: The breadth of the types of
      activities described suggests that a wide latitude is available to organizations
      in creating experiential education programs that reflect their individual program
      and institutional needs and resources.

PMID- 27046404
TI  - Medical Student Volunteerism Addresses Patients' Social Needs: A Novel Approach
      to Patient-Centered Care.
AB  - BACKGROUND: Healthcare providers must be equipped to recognize and address
      patients' psychosocial needs to improve overall health outcomes. To give future
      healthcare providers the tools and training necessary to identify and address
      psychosocial issues, Lankenau Medical Center in partnership with the Philadelphia
      College of Osteopathic Medicine designed the Medical Student Advocate (MSA)
      program. METHODS: The MSA program places volunteer second-year osteopathic
      medical students in care coordination teams at Lankenau Medical Associates, a
      primary care practice serving a diverse patient population in the Philadelphia,
      PA, region. As active members of the team, MSAs are referred high-risk patients
      who have resource needs such as food, employment, child care, and transportation.
      MSAs work collaboratively with patients and the multidisciplinary team to address
      patients' nonmedical needs. RESULTS: From August 2013 to August 2015, 31
      osteopathic medical students volunteered for the MSA program and served 369
      patients with 720 identified needs. Faculty and participating medical students
      report that the MSA program provided an enhanced understanding of the holistic
      nature of patient care and a comprehensive view of patient needs. CONCLUSION: The
      MSA program provides students with a unique educational opportunity that
      encompasses early exposure to patient interaction, social determinants of health,
      population health, and interdisciplinary collaboration. Students develop skills
      to help them build patient relationships, understand the psychosocial factors
      shaping health outcomes, and engage with other healthcare professionals. This
      work in the preclinical years provides students with the knowledge to help them
      perform more effectively in the changing healthcare environment.

PMID- 27046405
TI  - Virtues Education in Medical School: The Foundation for Professional Formation.
AB  - BACKGROUND: Studies have shown that medical students have high rates of burnout
      accompanied by a loss of empathy as they progress through their training. This
      article describes a course for medical students at The University of Queensland
      Ochsner Clinical School in New Orleans, LA, that focuses on the development of
      virtues and character strengths necessary in the practice of medicine. Staff of
      the Ochsner Clinical School and of the Institute of Medicine, Education, and
      Spirituality at Ochsner, a research and consulting group of Ochsner Health
      System, developed the course. It is a curricular innovation designed to
      explicitly teach virtues and their associated prosocial behaviors as a means of
      promoting professional formation among medical students. Virtues are core to the
      development of prosocial behaviors that are essential for appropriate
      professional formation. METHODS: Fourth-year medical students receive instruction
      in the virtues as part of the required Medicine in Society (MIS) course. The
      virtues instruction consists of five 3-hour sessions during orientation week of
      the MIS course and a wrapup session at the end of the 8-week rotation. Six
      virtues-courage, wisdom, temperance, humanity, transcendence, and justice-are
      taught in a clinical context, using personal narratives, experiential exercises,
      contemplative practices, and reflective practices. RESULTS: As of July 2015, 30
      medical students had completed and evaluated the virtues course. Ninety-seven
      percent of students felt the course was well structured. After completing the
      course, 100% of students felt they understood and could explain the character
      strengths that improve physician engagement and patient care, 100% of students
      reported understanding the importance of virtues in the practice of medicine, and
      83% felt the course provided a guide to help them deal with the complexities of
      medical practice. Ninety-three percent of students stated they would use the
      character strengths for their own well-being, and 90% said they would change
      their approach to the practice of medicine as a result of this course. Overall,
      92% of students rated the course as outstanding or good. CONCLUSION: We developed
      a course to teach virtues and their associated prosocial behaviors that are
      important for the practice of medicine. After completing the course, students
      self-reported improved understanding of the virtues and their importance to the
      practice of medicine. We plan further studies to determine if participation in
      the course leads to less burnout and improved resilience.

PMID- 27046406
TI  - Medicine Clerkship Implementation in a Hospitalist Group: Curricular Innovation
      and Review.
AB  - BACKGROUND: In 2008, the Department of Hospital Medicine at Ochsner Clinic
      Foundation in New Orleans, LA, began training its own students for the first time
      as a result of the partnership between our institution and the University of
      Queensland (UQ) in Brisbane, Australia, that established a global medical school.
      The Department of Hospital Medicine is responsible for the Medicine clerkship for
      third-year medical students. We have 5 resident teams at the main hospital in the
      system, but the majority of our hospitalists work alone. Because of staffing
      issues, we have had to change our mentality from having teaching hospitalists and
      nonteaching hospitalists to viewing all hospitalists as potential educators.
      METHODS: The department has slowly increased the number of students in the
      Medicine clerkship each year with the goal of training 120 third-year students in
      the New Orleans area in 2016. The students in the Medicine clerkship will be
      divided into five 8-week rotations, allowing for 25 students to be trained at one
      time. RESULTS: The UQ curriculum is similar to that of most 4-year American
      schools, but some differences in methods, such as a heavy emphasis on bedside
      instruction and oral summative assessments, are novel to us. These differences
      have provided our department with new goals for professional and instructor
      development. For the actual instruction, we pair students one on one with
      hospitalists and also assign them to resident teams. Student placement has been a
      challenge, but we are making improvements as we gain experience and explore
      opportunities for placement at our community hospitals. CONCLUSION: Our
      arrangement may be adapted to other institutions in the future as the number of
      students increases and the availability of resident teachers becomes more
      difficult nationwide.

PMID- 27046407
TI  - Comparing Pediatric Rotations at Two University of Queensland Clinical Schools.
AB  - BACKGROUND: The University of Queensland (UQ), Ochsner Clinical School (OCS) is a
      partnership between Ochsner Health System in New Orleans, LA, and UQ in Brisbane,
      Australia. OCS medical students are trained on both continents, receiving their
      didactic education in Australia and their clinical education in the United
      States. METHODS: We review the OCS experience and compare the pediatric rotations
      at OCS and UQ. RESULTS: Students in the pediatric rotations in Australia and in
      the United States receive their clinical instruction in the real-world learning
      environment of hospitals and clinics. In addition, lectures, online learning
      modules, case-based tutorials, and rigorous assessment at the end of the rotation
      help prepare medical students for future contact with pediatric patients. Sixty
      nine third-year OCS students and 499 fourth-year UQ students completed the
      pediatric rotation in 2014. In 2015, 105 third-year OCS students and
      approximately 400 fourth-year UQ students completed the pediatric rotation.
      CONCLUSION: In a unique educational collaboration, OCS has used e-learning and
      face-to-face tutorials to produce a well-rounded curriculum that assimilates
      global healthcare and international medicine. This article demonstrates the
      feasibility of delivering a standardized curriculum across two continents using
      modern e-learning tools.

PMID- 27046408
TI  - Developing Oral Case Presentation Skills: Peer and Self-Evaluations as
      Instructional Tools.
AB  - BACKGROUND: Oral case presentation is an essential skill in clinical practice
      that is decidedly varied and understudied in teaching curricula. METHODS: We
      developed a curriculum to improve oral case presentation skills in medical
      students. RESULTS: As part of an internal medicine clerkship, students receive
      instruction in the elements of a good oral case presentation and then present a
      real-world case in front of a video camera. Each student self-evaluates his/her
      presentation and receives evaluations from his/her peers. We expect peer and self
      evaluation to be meaningful tools for developing skills in oral presentation.
      CONCLUSION: We hope to not only improve the quality of oral case presentations by
      students but also to reduce the time burden on faculty.

PMID- 27046409
TI  - Flipping the Physical Examination: Web-Based Instruction and Live Assessment of
      Bedside Technique.
AB  - BACKGROUND: The skill of physicians teaching the physical examination skill has
      decreased, with newer faculty underperforming compared to their seniors. Improved
      methods of instruction with an emphasis on physical examinations are necessary to
      both improve the quality of medical education and alleviate the teaching burden
      of faculty physicians. METHODS: We developed a curriculum that combines web-based
      instruction with real-life practice and features individualized feedback.
      RESULTS: This innovative medical education model should allow the physical
      examination to be taught and assessed in an effective manner. The model is under
      study at Baton Rouge General Medical Center. CONCLUSION: Our goals are to limit
      faculty burden, maximize student involvement as learners and evaluators, and
      effectively develop students' critical skills in performing bedside assessments.

PMID- 27046410
TI  - Improving Patient Safety Event Reporting Among Residents and Teaching Faculty.
AB  - BACKGROUND: A June 2012 site visit report from the Accreditation Council for
      Graduate Medical Education Clinical Learning Environment Review revealed that
      residents and physicians at TriHealth, Inc., a large, nonprofit independent
      academic medical center serving the Greater Cincinnati area in Ohio, had an
      opportunity to improve their awareness and understanding of the hospital's system
      for reporting patient safety concerns in 3 areas: (1) what constitutes a
      reportable patient safety event, (2) who is responsible for reporting, and (3)
      how to use the hospital's current reporting system. METHODS: To improve the
      culture of patient safety, we designed a quality improvement project with the
      goal to increase patient safety event reporting among residents and teaching
      faculty. An anonymous questionnaire assessed physicians' and residents' attitudes
      and experience regarding patient safety event reporting. An educational
      intervention was provided in each graduate medical education program to improve
      knowledge and skills related to patient safety event reporting, and the anonymous
      questionnaire was distributed after the intervention. We compared the responses
      to the preintervention and postintervention questionnaires and tracked monthly
      patient safety event reports for 1 year postintervention. RESULTS: The number of
      patient safety event reports increased following the educational intervention;
      however, we saw wide variability in reporting per month. On the postintervention
      questionnaire, participants demonstrated improved knowledge and attitudes toward
      patient safety event reporting. CONCLUSION: The goal of this unique project was
      to increase patient safety event reporting by both residents and teaching faculty
      in 6 residency programs through education. We achieved this goal through an
      educational intervention tailored to the institution's new event reporting system
      delivered to each residency program. We clearly understand that improvements in
      quality and patient safety require ongoing effort. The keys to ongoing
      sustainability include (1) developing patient safety faculty and resident experts
      in each training program to teach patient safety and to be role models, (2)
      working toward decreasing the barriers to reporting, and (3) providing timely
      feedback and system changes.

PMID- 27046411
TI  - Graduate Medical Education as a Lever for Collaborative Change: One Institution's
      Experience with a Campuswide Patient Safety Initiative.
AB  - BACKGROUND: The 2013 closure of a public hospital in Baton Rouge, LA transformed
      graduate medical education (GME) at Our Lady of the Lake Regional Medical Center
      (OLOL). Administrators were tasked with incorporating residents into patient
      safety and quality improvement initiatives to fulfill regulatory obligations.
      This report outlines our experiences as we built these patient safety and quality
      improvement initiatives in a rapidly expanding independent academic medical
      center. METHODS: We joined the Alliance of Independent Academic Medical Centers
      (AIAMC) to meet and learn from national peers. To fulfill the scholarly activity
      requirement of the AIAMC's National Initiative IV, we formed a multidisciplinary
      team to develop a patient safety education project. Prioritized monthly team
      meetings allowed for project successes to be celebrated and circulated within the
      organization. RESULTS: The public-private partnership that more than quadrupled
      the historic size of GME at OLOL has, in the past 2 years, led to the development
      of an interdisciplinary team. This team has expanded to accommodate residency
      program leadership from across the campus. Our National Initiative IV project won
      a national award and inspired several follow-up initiatives. In addition, this
      work led to the formation of a Patient Safety and Clinical Quality Improvement
      fellowship that matched its first fellow in 2015. CONCLUSION: Through the
      commitment and support of hospital and medical education leaders, as well as a
      focus on promoting cultural change through scholarly activity, we were able to
      greatly expand patient safety and quality improvement efforts in our institution.

PMID- 27046412
TI  - Institutional Oversight of the Graduate Medical Education Enterprise: Development
      of an Annual Institutional Review.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      fully implemented all aspects of the Next Accreditation System (NAS) on July 1,
      2014. In lieu of periodic accreditation site visits of programs and institutions,
      the NAS requires active, ongoing oversight by the sponsoring institutions (SIs)
      to maintain accreditation readiness and program quality. METHODS: The Ochsner
      Health System Graduate Medical Education Committee (GMEC) has instituted a
      process that provides a structured, process-driven improvement approach at the
      program level, using a Program Evaluation Committee to review key performance
      data and construct an annual program evaluation for each accredited residency.
      The Ochsner GMEC evaluates the aggregate program data and creates an Annual
      Institutional Review (AIR) document that provides direction and focus for ongoing
      program improvement. This descriptive article reviews the 2014 process and
      various metrics collected and analyzed to demonstrate the program review and
      institutional oversight provided by the Ochsner graduate medical education (GME)
      enterprise. RESULTS: The 2014 AIR provided an overview of performance and quality
      of the Ochsner GME program for the 2013-2014 academic year with particular
      attention to program outcomes; resident supervision, responsibilities,
      evaluation, and compliance with duty-hour standards; results of the ACGME survey
      of residents and core faculty; and resident participation in patient safety and
      quality activities and curriculum. The GMEC identified other relevant
      institutional performance indicators that are incorporated into the AIR and
      reflect SI engagement in and contribution to program performance at the
      individual program and institutional levels. CONCLUSION: The Ochsner GME office
      and its program directors are faced with the ever-increasing challenges of
      today's healthcare environment as well as escalating institutional and program
      accreditation requirements. The overall commitment of this SI to advancing our
      GME enterprise is clearly evident, and the opportunity for continued improvement
      resulting from institutional oversight is being realized.

PMID- 27046413
TI  - Using Computerized Physician Order Entry to Ensure Appropriate Vaccination of
      Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a disorder in which an aberrant
      immune response in a genetically susceptible host, with influences from
      environmental factors, leads to intestinal inflammation. Vaccines against
      influenza and pneumococcal pneumonia are indicated for all patients with IBD,
      while vaccines such as hepatitis A and B, human papillomavirus, and meningococcal
      meningitis are only indicated for patients with specific risk factor profiles.
      Some vaccines are contraindicated for patients receiving immunosuppressive
      medications; typically, these are live or live attenuated vaccines such as
      measles-mumps-rubella, varicella zoster, and herpes zoster. Given the importance
      of ensuring patients with IBD are properly vaccinated, we designed a quality
      improvement project to determine the perceived barriers to ordering these
      vaccines and to make the process easier. METHODS: At the outset of the study,
      providers in our gastroenterology department who treat patients with IBD received
      a survey about vaccinations. Based on the preintervention survey responses, we
      created an order panel in our electronic medical record (Epic Systems
      Corporation) to facilitate vaccination ordering. This order panel prompted
      physicians to order the vaccinations and informed them of contraindications. At
      the end of the 2-month implementation period, we distributed a second survey to
      assess the utility of the order panel. RESULTS: Respondents generally agreed that
      the Epic SmartSet order panel made vaccinations easier to order, ensured
      physician confidence in ordering vaccinations, was helpful for use in practice,
      made the clinic more efficient, and reminded physicians which vaccinations are
      contraindicated because of immunosuppression. Respondents were divided regarding
      whether a greater number of patients with IBD were actually receiving
      vaccinations after the order panel was implemented. CONCLUSION: We used the order
      entry function in Epic to facilitate vaccination ordering for patients with IBD.
      Our results indicate that the order panel we built made ordering vaccinations
      easier and more efficient compared to the previous process. We hope this order
      panel promotes improved patient care and becomes a future area of study for how
      Epic and other electronic health records may be used.

PMID- 27046414
TI  - A Multidisciplinary Intervention to Prevent Catheter-Associated Urinary Tract
      Infections Using Education, Continuum of Care, and Systemwide Buy-In.
AB  - BACKGROUND: In 2012, the Scottsdale Osborn Medical Center intensive care unit
      (ICU) had a rate of catheter-associated urinary tract infection (CAUTI) among the
      highest in Arizona hospitals, with 54 infections reported. To address the high
      rate of CAUTI in the Osborn campus ICU, the project team participating in the
      Alliance of Independent Academic Medical Centers (AIAMC) National Initiative IV
      joined the CAUTI systemwide oversight team in the ambitious goal to eliminate
      CAUTI from Scottsdale Healthcare. METHODS: The quality improvement project to
      eliminate CAUTI took place throughout calendar year 2014 at the Osborn campus and
      involved the AIAMC project team, the CAUTI systemwide oversight team, and support
      from the Scottsdale Healthcare information technology team. A CAUTI bundle based
      on current best-practice guidelines for prevention of CAUTI was finalized in
      January 2014. In addition, the AIAMC project team spearheaded and coordinated 6
      initiatives based on current guidelines to attempt to reduce unnecessary urinary
      catheter use in the hospital system. The initiatives included education,
      mandatory prompts and reminders in the electronic medical record, daily patient
      tracking, a resident quality champion, and a urine retention protocol. RESULTS:
      Catheter days in the ICU dropped by approximately one-third during the first 2
      quarters of 2014 and then appeared to level off. The CAUTI numbers and rate
      fluctuated in the ICU without much change during 2013 and 2014 but then dropped
      in 2015. However, the national definition of CAUTI changed in the first quarter
      of 2015, and the change in definition was estimated to reduce the number of
      reported CAUTIs in our hospital by 25%-30%. Urinary catheter days in the non-ICU
      units declined relatively steadily from the last quarter of 2013 through midyear
      2015. CAUTI rates were fairly low in this setting during the observed quarters.
      In the emergency department (ED), both urinary catheter insertions and the
      insertion rate dropped during 2014. The insertion rate dropped from approximately
      4% of all ED patients prior to the initiative to just 1%. CONCLUSION: The
      greatest success of this AIAMC National Initiative IV project was the dramatic
      and sustained decrease in urinary catheter insertions in the ED. The project also
      helped achieve an important reduction in urinary catheter days in the target
      hospital ICU and non-ICU floors and likely helped to reduce CAUTI rates as well.
      Intensive education efforts involving nurses, residents, attending physicians,
      and quality improvement staff were crucial elements in the initiative. Tracking
      patients with urinary catheters and electronic order entry and stop reminders
      played an important role. Despite progress, much work remains to eliminate CAUTI
      from the hospital.

PMID- 27046415
TI  - Multigenerational Challenges and the Future of Graduate Medical Education.
AB  - BACKGROUND: Demographics are changing on a global scale. In the United States, an
      aging population continues to work, either by preference or because of
      insufficient resources to retire. Of even greater importance, a younger
      generation, referred to as the Millennial Generation, will soon predominate in
      the workforce and even now accounts for nearly 100% of resident physicians. By
      the year 2020, there will be 5 generations in the workplace. METHODS: This paper
      defines and details the characteristics of the 5 generations and examines how the
      vision, attitudes, values, and expectations of the most recent generations will
      reshape the workforce and graduate medical education. RESULTS: The need for
      change is imminent to educate the next generation of physicians. Among the
      changes necessary to adapt to the multigenerational challenges ahead are adopting
      mobile devices as preferred communication tools; using social networking sites to
      recruit residents; adding games, simulations, and interactive videos to the
      curriculum to engage students; breaking down departmental silos and forming
      learning teams that come from different specialties; developing benchmarks and
      milestones to measure progress; extending the social learning ecosystem beyond
      the resident years; embracing diversity as the norm for both practice and
      learning; and providing both coaching and mentoring. CONCLUSION: For decades,
      resident physicians have shown commitment, tenacity, and selflessness while
      shouldering the dual responsibility of patient care and the pursuit of their own
      education and skills development. Resident engagement has been shown to drive
      change in undergraduate medical education and in the learning and performance of
      their teachers. The latter is evidence of reverse mentoring that will be a major
      factor for improvement in this digital age. We have only to embrace this
      opportunity to the benefit of our patients, our learners, and ourselves.

PMID- 27046416
TI  - Impact of parity on bone metabolism throughout the reproductive cycle in sows.
AB  - Bone metabolism fluctuates throughout the reproductive cycle of sows to enable
      foetal growth and milk production. Although increased bone mineralisation is
      conceivable in sows during reproduction, a study of mineralisation in function of
      parity has not been performed. This study evaluated the fluctuations of markers
      for bone metabolism in primiparous and multiparous sows throughout a reproductive
      cycle. The experiment included ten multiparous and five primiparous commercial
      hybrid sows from one herd. The sows were monitored for one reproductive cycle and
      fed according to commercial dietary standards. Blood samples were taken in the
      morning before feeding at fixed time intervals before (day -5) and during
      gestation (insemination (day 0), 21, 42, 63, 84), around parturition (day 108,
      112, parturition (115), 118), and during lactation (day 122, 129, 143). Serum
      osteocalcin (OC) concentration increased in early and mid-gestation (P=0.002) and
      decreased at the end of gestation (P=0.001), whereas crosslaps (CTX)
      concentration decreased during early and mid-gestation (P=0.002) and increased
      towards the end of gestation (P=0.001). Towards the end of lactation serum levels
      of both markers increased (P=0.007 and 0.013, respectively). For hydroxyproline
      (HYP) no significant fluctuation in function of the reproductive cycle was
      detected. Matrix metalloproteinase 2 (MMP2) concentration increased towards
      parturition for both primiparous and multiparous sows (P=0.001), whereas during
      lactation no significant fluctuations in function of the reproductive cycle were
      found. A parity effect was found for OC and CTX (P<0.010), but not for the other
      markers. These results demonstrate that bone metabolism differed between
      primiparous and multiparous sows, although in both groups a similar fluctuation
      throughout the reproductive cycle was observed.

PMID- 27046417
TI  - An Experimental and Theoretical Investigation of the C((1)D) + N2 -> C((3)P) + N2
      Quenching Reaction at Low Temperature.
AB  - The gas-phase quenching reaction C((1)D) + N2 -> C((3)P) + N2 has been
      investigated experimentally over the temperature range 50-296 K using a
      supersonic flow reactor. C((1)D) atoms were produced in situ by the pulsed
      multiphoton dissociation of CBr4 precursor molecules. Rate constants for this
      process were measured using a chemical tracer method whereby the C((1)D) + H2 ->
      CH + H reaction was employed to follow C((1)D) decays by monitoring vacuum
      ultraviolet laser-induced fluorescence of the atomic hydrogen product at 121.567
      nm. The deactivation rates are seen to increase at lower temperature, indicating
      the likely influence of the CNN intermediate complex lifetime on intersystem
      crossing for this system. We also performed electronic structure calculations of
      relevant C((3)P)-N2 and C((1)D)-N2 potential energy curves as well as triplet
      singlet spin-orbit coupling terms using the explicitly correlated internally
      contracted multireference configuration interaction method (ic-MRCI-F12). The
      calculations were performed for the collinear and perpendicular approach of the C
      atom toward the N2 molecule, which allowed us to construct the approximate
      spherical (isotropic) potential model of C-N2(j = 0). The computed reduced
      dimensional potentials were used in quantum close coupling scattering
      calculations of the electronic quenching cross sections and rate constants. While
      the calculated potential energy curves form the basis for a good qualitative
      description of the reaction, the calculated rate constants are significantly
      smaller than the measured ones, and fail to reproduce the temperature dependence
      of the experimental results. Several possible reasons are provided to explain the
      origin of these differences.

PMID- 27046418
TI  - No more time to stay 'single' in the detection of Anisakis pegreffii, A. simplex
      (s. s.) and hybridization events between them: a multi-marker nuclear genotyping
      approach.
AB  - A multi-marker nuclear genotyping approach was performed on larval and adult
      specimens of Anisakis spp. (N = 689) collected from fish and cetaceans in
      allopatric and sympatric areas of the two species Anisakis pegreffii and Anisakis
      simplex (s. s.), in order to: (1) identify specimens belonging to the parental
      taxa by using nuclear markers (allozymes loci) and sequence analysis of a new
      diagnostic nuclear DNA locus (i.e. partial sequence of the EF1 alpha-1 nDNA
      region) and (2) recognize hybrid categories. According to the Bayesian clustering
      algorithms, based on those markers, most of the individuals (N = 678) were
      identified as the parental species [i.e. A. pegreffii or A. simplex (s. s.)],
      whereas a smaller portion (N = 11) were recognized as F1 hybrids. Discordant
      results were obtained when using the polymerase chain reaction-restriction
      fragment length polymorphisms (PCR-RFLPs) of the internal transcribed spacer
      (ITS) ribosomal DNA (rDNA) on the same specimens, which indicated the occurrence
      of a large number of 'hybrids' both in sympatry and allopatry. These findings
      raise the question of possible misidentification of specimens belonging to the
      two parental Anisakis and their hybrid categories derived from the application of
      that single marker (i.e. PCR-RFLPs analysis of the ITS of rDNA). Finally,
      Bayesian clustering, using allozymes and EF1 alpha-1 nDNA markers, has
      demonstrated that hybridization between A. pegreffii and A. simplex (s. s.) is a
      contemporary phenomenon in sympatric areas, while no introgressive hybridization
      takes place between the two species.

PMID- 27046419
TI  - Comparative Study of Cl-Atom Reactions in Solution Using Time-Resolved
      Vibrational Spectroscopy.
AB  - A Cl atom can react with 2,3-dimethylbutane (DMB), 2,3-dimethyl-2-butene (DMBE),
      and 2,5-dimethyl-2,4-hexadiene (DMHD) in solution via a hydrogen-abstraction
      reaction. The large exoergicity of the reaction between a Cl atom and alkenes
      (DMBE and DMHD) makes vibrational excitation of the HCl product possible, and we
      observe the formation of vibrationally excited HCl (v = 1) for both reactions. In
      CCl4, the branching fractions of HCl (v = 1), Gamma (v = 1), for the Cl-atom
      reactions with DMBE and DMHD are 0.14 and 0.23, respectively, reflecting an
      increased amount of vibrational excitation in the products of the more exoergic
      reaction. In addition, Gamma (v = 1) for both reactions is larger in the solvent
      CDCl3, being 0.23 and 0.40, as the less viscous solvent apparently dampens the
      vibrational excitation of the nascent HCl less effectively. The bimolecular
      reaction rates for the Cl reactions with DMB, DMBE, and DMHD in CCl4 are
      diffusion limited (having rate constants of 1.5 * 10(10), 3.6 * 10(10), and 17.5
      * 10(10) M(-1) s(-1), respectively). In fact, the bimolecular reaction rate for
      Cl + DMHD exceeds a typical diffusion-limited reaction rate, implying that the
      attractive intermolecular forces between a Cl atom and a C?C bond increase the
      rate of favorable encounters. The 2-fold increase in the reaction rate of the Cl
      + DMBE reaction from that of the Cl + DMB reaction likely reflects the effect of
      the C?C bond, while both the number of C?C bonds and the molecular geometry
      likely play a role in the large reaction rate of the Cl + DMHD reaction.

PMID- 27046420
TI  - Prolonged biochemical response after discontinuation of orteronel (TAK-700) in a
      patient with metastasized castration-resistant prostate cancer.

PMID- 27046421
TI  - Histone Acetylation Induced Transformation of B-DNA to Z-DNA in Cells Probed
      through FT-IR Spectroscopy.
AB  - A nucleosome is made up of DNA and histones, and acetylation of histones perturbs
      the interaction of DNA and histones and thus affects the chromatin conformation
      and function. However, whether or how acetylation induces DNA conformation
      changes is still elusive. In this work, we applied FT-IR spectroscopy to monitor
      the DNA signals in cells as the histone acetylation was regulated by trichostatin
      A (TSA), a reversible inhibitor to histone deacetylases (HDACs). Our results
      unambiguously demonstrate the significant transformation of B-DNA to Z-DNA upon
      histone acetylation in the TSA treated HeLa cells. This is the first report
      providing the explicit experimental evidence for such a B-Z transformation of DNA
      in the epigenetic states of cells. 

PMID- 27046423
TI  - Living with lymphoedema for over 50 years.

PMID- 27046422
TI  - How low should we go: A systematic review and meta-analysis of the impact of
      restrictive red blood cell transfusion strategies in oncology.
AB  - BACKGROUND: Most non-oncologic clinical practice guidelines recommend restrictive
      allogeneic blood transfusion practices; however, there is a lack of consensus
      regarding the best transfusion practice in oncology. We conducted a systematic
      review of the literature to compare the efficacy and safety of restrictive versus
      liberal transfusion strategies in patients with cancer. METHODS: A literature
      search using MEDLINE, PUBMED and EMBASE identified all controlled studies
      comparing the use of restrictive with liberal transfusion in adult oncology
      participants up to August 10, 2015. Two review authors independently assessed
      studies for inclusion, extracted data and appraised the quality of the included
      studies. The primary outcomes of interest were blood utilization and all-cause
      mortality. RESULTS: Out of 4241 citations, six studies (3 randomized and 3 non
      randomized) involving a total of 983 patients were included in the final review.
      The clinical context of the studies varied with 3 chemotherapy and 3 surgical
      studies. The overall risk of bias in all studies was moderate to high.
      Restrictive transfusion strategies were associated with a 36% reduced risk of
      receiving a perioperative transfusion (risk ratio (RR) 0.64, 95% confidence
      interval (CI) 0.49-0.83). There was no difference in mortality between the
      strategies (RR 1.00, 95% CI 0.32-3.18). There were no differences in adverse
      events reported between the restrictive and liberal transfusion strategies.
      CONCLUSION: Restrictive strategy appears to decrease blood utilization without
      increasing morbidity or mortality in oncology. This review is limited by a
      paucity of high quality studies on this topic. Better designed studies are
      warranted.

PMID- 27046424
TI  - Managing chronic oedema in a patient with arterial disease and leg ulceration.
AB  - Treating lymphoedema in patients with critical arterial disease can be
      contraindicated. This case study describes current methods of managing
      lymphoedema in a patient with arterial disease and leg ulcers. The patient, a 65
      year-old male, had paraplegia and lower-limb lymphoedema with leg ulceration for
      18 years, as well as arterial disease. The patient was referred to the
      lymphoedema/vascular service in 2013. Duplex ultrasound indicated superficial
      femoral occlusion. The arterial disease was treated with an angiogram and
      angioplasty, and when the blood supply was improved, the lymphoedema was treated.
      Emphasis was placed on self-care and reducing the need for community nurse
      involvement. Selfcare included compression bandaging, use of FarrowWrap, low
      level light therapy, and ulcer dressings. Outcomes were measured using a
      telemedicine software programme. The patient's lymphoedema was reduced, leg
      ulcers healed, and quality of life transformed. 

PMID- 27046425
TI  - Managing chronic oedema and venous disease with made-to-order garments.
AB  - Selecting the most appropriate compression garments is vital in the long-term
      management of venous disease and chronic oedema. The range of styles has improved
      greatly over the years and many garments are available on the UK Drug Tariff.
      Practitioners now have a wide range of options to choose from including the type
      of fabric, colour, compression class, and style of garment. These options
      increase the pratitioner's ability to select the most suitable garments and
      combine clinical and aesthetic needs, with the ultimate aim of improving
      compliance. The focus of this article is to highlight the aims and qualities of
      the various types of compression garments available, discuss the rationale for
      prescribing choice, and describe the benefits of Haddenham's Veni made-to-order
      compression leg garments in the management of chronic oedema and venous disease.
      Three case studies will demonstrate the effectiveness of the Veni made-to-order
      range of compression garments. 

PMID- 27046426
TI  - Specialist approaches to managing lipoedema.
AB  - While there is no proven cure for lipoedema, early detection is key as specialist
      treatments, complemented by self-management techniques, can improve symptoms and
      prevent progression. There is no universal approach as the correct treatment or
      treatments will depend on each patient's particular circumstances; however, when
      chosen early and appropriately, interventions can provide huge benefits. The most
      common treatments in the management of lipoedema include compression, manual
      lymphatic drainage (MLD), tumescent liposuction, intermittent pneumatic
      compression therapy (IPC), kinesio taping, deep oscillation therapy, and
      cognitive behavioural therapy (CBT). 

PMID- 27046427
TI  - An acupuncturist and MLD therapist.

PMID- 27046428
TI  - Assuring holistic treatment and care for all patients.

PMID- 27046429
TI  - The National Lymphoedema Partnership.

PMID- 27046430
TI  - 2016: a busy year for the LSN.

PMID- 27046431
TI  - Lymphoedema care: continually evolving.

PMID- 27046432
TI  - Prevalence of lymphoedema in the UK: focus on the southwest and West Midlands.
AB  - The aim of this research study was to estimate the potential prevalence of
      lymphoedema and the causes for this prevalence within two regions in England.
      This study is one of the first to undertake such a comparison in England and
      complements existing studies. The study calculates a regional prevalence figure
      for the Southwest (SW) of 3.59:1000 and 2.29:1000 in the West Midlands (WM). The
      local variation in the regions is 0.98-8.81:1000 for SW and 0.78-15.3:1000 for
      WM. Patient diagnosis of primary lymphoedema was 1:5129 in the SW compared with
      1:2763 in the WM. These figures have relevance to patient care when considering
      population needs in the commissioning of services and the effect of wider
      determinants of health. Recommendations consider the need for national policy and
      the availability of education and training. Further research is required in both
      regions to consider age and gender set against diagnosis. Despite raising
      additional questions, the study has offered an opportunity to explore the effect
      of lymphoedema within the chosen regions. 

PMID- 27046433
TI  - Analysis of a government policy to address nursing shortage and nursing education
      quality.
AB  - BACKGROUND: A well-educated, sufficient nursing workforce improves population
      health and standards of nursing care. Analysing workforce policies assists nurses
      to learn from the past and develop better future policies. AIM: Describe policy
      making processes in the first Thai government plan to increase nursing capacity
      and improve nursing education quality. DESIGN: A qualitative study employing
      Longest's model to examine policy-making processes. METHODS: Data were obtained
      from 28 in-depth interviews with key informants, who had been committee members
      and former deans of nursing involved with the policy processes in the 1990s. Both
      qualitative and quantitative data were extracted from relevant documents, and
      content analysis employed with all data. FINDINGS: Three policy phases were
      identified. Policy formulation, where three streams of problems, politics and
      policy resulted in identification of nursing shortage, changes of government
      incumbents and needing to increase nurse production; Policy implementation
      included creating methods of implementation, appointing responsible people and
      committees, creating operational plans, producing more nurses and faculty
      development projects and Policy modification which incorporated implementing the
      first Thai international doctoral degree in English, a collaborative programme
      between universities. STUDY LIMITATIONS: Not all key informants could be accessed
      due to the passage of time. Findings are unique to Thailand but inform
      internationally of nurses' abilities and need to be involved in policy.
      CONCLUSION: Nurses were involved in all policy phases. While the policy produced
      positive developments in growing nursing capacity and education in the past,
      nursing shortages remained and are now acute in Thailand. IMPLICATIONS FOR
      NURSING/HEALTH POLICY: Lessons learned from this policy analysis help explain why
      the nursing education and nursing shortage policy was legislated through the
      government agenda, and the active involvement of Thai nurses in this process.
      Nurses globally need to be at the policy-making table to try to reduce nursing
      shortages, and enhance practice and education environments.

PMID- 27046434
TI  - Food and value motivation: Linking consumer affinities to different types of food
      products.
AB  - This study uses the consumer affinity concept to examine the multiple motives
      that may shape consumers' relationships with food. The concept was applied in a
      study on four broad product types in the Netherlands, which cover a wide range of
      the market and may each appeal to consumers with different affinities towards
      foods. These product types may be denoted as 'conventional', 'efficient',
      'gourmet' and 'pure'. A comparative analysis, based on Higgins' Regulatory Focus
      Theory, was performed to examine whether food-related value motivations could
      explain different consumer affinities for these product types. The affinities of
      consumers were measured by means of a non-verbal, visual presentation of four
      samples of food products in a nationwide survey (n = 742) among consumers who
      were all involved in food purchasing and/or cooking. The affinities found could
      be predicted fairly well from a number of self-descriptions relating to food and
      eating, which expressed different combinations of type of value motivation and
      involvement with food. The analysis demonstrated the contrasting role of high and
      low involvement as well as the potential complementarity of promotion- and
      prevention-focused value motivation. It is suggested that knowledge of the
      relationships between product types, consumer affinities and value motivation can
      help improve the effectiveness of interventions that seek to promote healthy and
      sustainable diets in developed countries.

PMID- 27046435
TI  - Haploinsufficiency of SF-1 Causes Female to Male Sex Reversal in Nile Tilapia,
      Oreochromis niloticus.
AB  - Steroidogenic factor-1 (Sf-1) (officially designated nuclear receptor subfamily 5
      group A member 1 [NR5A1]) is a master regulator of steroidogenesis and
      reproduction in mammals. However, its function remains unclear in nonmammalian
      vertebrates. In the present study, we used immunohistochemistry to detect
      expression of Sf-1 in the steroidogenic cells, the interstitial, granulosa, and
      theca cells of the ovary, and the Leydig cells of the testis, in Nile tilapia.
      Clustered regularly interspaced short palindromic repeats/CRISPR associated
      protein 9 (Cas9) cleavage of sf-1 resulted in a high mutation rate in the F0
      generation and a phenotype of gonadal dysgenesis and reduced steroidogenic cells
      in XX and XY fish. Sf-1 deficiency also resulted in decreased cytochrome P450,
      family 19, subfamily A, polypeptide 1a, forkhead box L2 expression, and serum
      estradiol-17beta in XX fish. In XY fish, Sf-1 deficiency increased cytochrome
      P450, family 19, subfamily A, polypeptide 1a and forkhead box L2 expression but
      decreased cytochrome P450, family 11, subfamily B, polypeptide 2 expression and
      serum 11-ketotestosterone levels. 17alpha-methyltestosterone treatment
      successfully rescued the gonadal phenotype of Sf-1-deficient XY fish, as
      demonstrated by normal spermatogenesis and production of F1 mutants. In contrast,
      estradiol-17beta treatment only partially rescued the gonadal phenotype of Sf-1
      deficient XX fish, as demonstrated by the appearance of phase II oocytes.
      Furthermore, both sf-1(+/-) F1 XX and XY mutants developed as fertile males,
      although spermatogenesis was delayed and efferent duct formation was disordered.
      Our data suggest that Sf-1 is a major regulator of steroidogenesis and
      reproduction in fish, as it is in mammals. Sf-1 deficiency resulted in gonadal
      dysgenesis and feminization of XY gonads. However, unlike in mammals, Sf-1
      deficiency also resulted in female to male sex reversal in 8.1% of F0 and 92.1%
      of sf-1(+/-) F1 in XX fish.

PMID- 27046436
TI  - Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Regulates the
      Hypothalamo-Pituitary-Thyroid (HPT) Axis via Type 2 Deiodinase in Male Mice.
AB  - The hypothalamic activation of thyroid hormones by type 2 deiodinase (D2),
      catalyzing the conversion of thyroxine to T3, is critical for the proper function
      of the hypothalamo-pituitary-thyroid (HPT) axis. Regulation of D2 expression in
      tanycytes alters the activity of the HPT axis. However, signals that regulate D2
      expression in tanycytes are poorly understood. The pituitary adenylate cyclase
      activating polypeptide (PACAP) increases intracellular cAMP level, a second
      messenger known to stimulate the DIO2 gene; however, its importance in tanycytes
      is not completely characterized. Therefore, we tested whether this ubiquitously
      expressed neuropeptide regulates the HPT axis through stimulation of D2 in
      tanycytes. PACAP increased the activity of human DIO2 promoter in luciferase
      reporter assay that was abolished by mutation of cAMP-response element.
      Furthermore, PAC1R receptor immunoreactivity was identified in hypothalamic
      tanycytes, suggesting that these D2-expressing cells could be regulated by PACAP.
      Intracerebroventricular PACAP administration resulted in increased D2 activity in
      the mediobasal hypothalamus, suppressed Trh expression in the hypothalamic
      paraventricular nucleus, and decreased Tshb expression in the pituitary
      demonstrating that PACAP affects the D2-mediated control of the HPT axis. To
      understand the role of endogenous PACAP in the regulation of HPT axis, the effect
      of decreased PACAP expression was studied in heterozygous Adcyap1 (PACAP)
      knockout mice. These animals were hypothyroid that may be the consequence of
      altered hypothalamic T3 degradation during set-point formation of the HPT axis.
      In conclusion, PACAP is an endogenous regulator of the HPT axis by affecting T3
      mediated negative feedback via cAMP-induced D2 expression of tanycytes.

PMID- 27046437
TI  - Mean-field and linear regime approach to magnetic hyperthermia of core-shell
      nanoparticles: can tiny nanostructures fight cancer?
AB  - The phenomenon of heat dissipation by magnetic materials interacting with an
      alternating magnetic field, known as magnetic hyperthermia, is an emergent and
      promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia
      model for core-shell nanoparticles is developed. The theoretical calculation,
      different from previous models, highlights the importance of heterogeneity by
      identifying the role of surface and core spins on nanoparticle heat generation.
      We found that the most efficient nanoparticles should be obtained by selecting
      materials to reduce the surface to core damping factor ratio, increasing the
      interface exchange parameter and tuning the surface to core anisotropy ratio for
      each material combination. From our results we propose a novel heat-based
      hyperthermia strategy with the focus on improving the heating efficiency of small
      sized nanoparticles instead of larger ones. This approach might have important
      implications for cancer treatment and could help improving clinical efficacy. 

PMID- 27046439
TI  - Drug-induced cholestasis risk assessment in sandwich-cultured human hepatocytes.
AB  - Drug-induced cholestasis (DIC) is recognized as one of the prime mechanisms for
      DILI. Hence, earlier detection of drug candidates with cholestatic signature is
      crucial. Recently, we introduced an in vitro model for DIC and evaluated its
      performance with several cholestatic drugs. We presently expand on the validation
      of this model by 14 training compounds (TCs) of the EU-EFPIA IMI project MIP
      DILI. Several batches of human hepatocytes in sandwich-culture were qualified for
      DIC assessment by verifying the bile acid-dependent increase in sensitivity to
      the toxic effects of cyclosporin A. The cholestatic potential of the TCs was
      expressed by determining the drug-induced cholestasis index (DICI). A safety
      margin (SM) was calculated as the ratio of the lowest TC concentration with a
      DICI<=0.80 to the Cmax,total. Nefazodone, bosentan, perhexiline and troglitazone
      were flagged for cholestasis (SM<30). The hepatotoxic (but non-cholestatic)
      compounds, amiodarone, diclofenac, fialuridine and ximelagatran, and all non
      hepatotoxic compounds were cleared as "safe" for DIC. Tolcapone and paracetamol
      yielded DICI-based SM values equal to or higher than those based on cytotoxicity,
      thus excluding DIC as a DILI mechanism. This hepatocyte-based in vitro assay
      provides a unique tool for early and reliable identification of drug candidates
      with cholestasis risk. 

PMID- 27046438
TI  - Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric
      immunoglobulin receptor deficiency.
AB  - Mechanisms driving persistent airway inflammation in chronic obstructive
      pulmonary disease (COPD) are incompletely understood. As secretory immunoglobulin
      A (SIgA) deficiency in small airways has been reported in COPD patients, we
      hypothesized that immunobarrier dysfunction resulting from reduced SIgA
      contributes to chronic airway inflammation and disease progression. Here we show
      that polymeric immunoglobulin receptor-deficient (pIgR(-/-)) mice, which lack
      SIgA, spontaneously develop COPD-like pathology as they age. Progressive airway
      wall remodelling and emphysema in pIgR(-/-) mice are associated with an altered
      lung microbiome, bacterial invasion of the airway epithelium, NF-kappaB
      activation, leukocyte infiltration and increased expression of matrix
      metalloproteinase-12 and neutrophil elastase. Re-derivation of pIgR(-/-) mice in
      germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4
      inhibitor roflumilast prevents COPD-like lung inflammation and remodelling. These
      findings show that pIgR/SIgA deficiency in the airways leads to persistent
      activation of innate immune responses to resident lung microbiota, driving
      progressive small airway remodelling and emphysema. 

PMID- 27046440
TI  - Left ventricular function measurements in a mouse myocardial infarction model.
      Comparison between 3D-echocardiography and ECG-gated SPECT.
AB  - AIM: To assess the accuracy of ECG-gated micro (u)-SPECT in a mouse myocardial
      infarction (MI) model in comparison to 3D-echocardiography. ANIMALS, METHODS: In
      a mouse (Swiss mice) MI model we compared the accuracy of technetium-99m
      sestamibi (99mTc-sestamibi) myocardial perfusion, electrocardiogram (ECG) gated
      uSPECT to 3D-echocardiography in determining left ventricular function. 3D
      echocardiography and myocardial perfusion ECG-gated uSPECT data were acquired in
      the same animal at baseline (n = 11) and 7 (n = 8) and 35 (n = 9) days post
      ligation of the left anterior descending coronary artery (LAD). Sham operated
      mice were used as a control (8, 6 and 7 mice respectively). Additionally, after
      day 35 uSPECT scans, hearts were harvested and 2,3,5-triphenyl-2H-tetrazolium
      chloride (TTC) staining and autoradiography was performed to determine infarct
      size. RESULTS: In both infarcted and sham-operated mice we consistently found
      comparable values for the end-diastolic volume (EDV), end-systolic volume (ESV)
      and ejection fraction (EF) obtained by 3D-echocardiography and ECG-gated uSPECT.
      Excellent correlations between measurements from 3D-echocardiography and ECG
      gated uSPECT were found for EDV, ESV and EF (r = 0.9532, r = 0.9693 respectively
      and r = 0.9581) in infarcted mice. Furthermore, comparable infarct size values
      were found at day 35 post MI by TTC staining and autoradiography (27.71 +/- 1.80%
      and 29.20 +/- 1.18% with p = 0.43). CONCLUSION: We have demonstrated that ECG
      gated uSPECT imaging provides reliable left ventricular function measurements in
      a mouse MI model. Obtained results were comparable to the highly accurate 3D
      echocardiography. This, in addition to the opportunity to simultaneously image
      multiple biological processes during a single acquisition makes uSPECT imaging a
      serious option for studying cardiovascular disease in small animals.

PMID- 27046441
TI  - Eltrombopag after allogeneic haematopoietic cell transplantation in a case of
      poor graft function and systematic review of the literature.
AB  - BACKGROUND: Late graft failure after allogeneic haematopoietic cell
      transplantation (HCT) can result from the failed engraftment of long-term
      engrafting cells. The use of thrombopoietin (TPO) receptor agonists (TRA) has
      been extensively studied and remains an important component of experimental ex
      vivo stem cell expansion protocols, but its use in allogeneic transplantation is
      still evolving. METHODS: We describe the use of eltrombopag, a TRA, to stimulate
      the rescue of late graft failure in a patient following allogeneic HCT, and we
      performed a systematic review of published studies describing the use of TRAs
      following allogeneic transplantation. RESULTS: A total of eight publications were
      identified from our systematic search and included observational case studies
      (five studies, total of seven patients) that primarily addressed ITP or isolated
      thrombocytopenia at various time points after allogeneic HCT and prospective
      clinical trials (three studies, total of 177 patients with 95 patients receiving
      TRAs). No studies reported specifically on the use of TRAs for the treatment of
      trilineage graft failure as a means of in vivo stem cell expansion. The use of
      TRAs following allogeneic HCT appears safe and promising. CONCLUSION: The use of
      eltrombopag or other TRAs to treat poor graft function after allogeneic HCT is
      intriguing and warrants further study.

PMID- 27046442
TI  - Iron treatment and the TREAT trial.
AB  - Treatment with erythropoiesis-stimulating agents (ESAs) enables the correction of
      anaemia in chronic kidney disease (CKD) patients, thus reducing its symptoms and
      complications. Not only is iron therapy aimed at correcting iron deficiency, but
      also it is an adjuvant therapy in CKD patients receiving ESAs. Iron stores in CKD
      patients may be near normal, but there may be insufficient immediately available
      iron to optimize ESA therapy. In this context, iron therapy significantly reduces
      ESA dose requirements. Erythropoiesis following ESA therapy may precipitate iron
      deficiency in association with increased platelet production. In the TREAT trial,
      the 'placebo group' did not receive a true 'placebo' since 46% of the patients
      had at least one dose of ESA and achieved progressively increased haemoglobin
      (Hb) values during follow-up against the common observation. The patients in the
      'placebo' group were treated more frequently with intravenous iron than the
      darbepoetin group. Given that many patients were relatively iron deficient at
      baseline, iron administration was successful in many of them in obtaining and
      maintaining partial anaemia correction without the need for ESAs, thus
      underlining the great importance of iron supplementation in correcting anaemia.
      The upper safety limit for iron administered to patients in order to minimize, as
      much as possible, the ESA dose and the upper limit for ESA dosage for maintaining
      the target Hb range as suggested by the current guidelines are still open
      questions.

PMID- 27046443
TI  - A prospective randomized double-blinded controlled trial evaluating indocyanine
      green fluorescence angiography on reducing wound complications in complex
      abdominal wall reconstruction.
AB  - BACKGROUND: The purpose of this prospective, randomized, double-blinded
      controlled trial was to investigate the utility of indocyanine green fluorescence
      angiography (ICG-FA) in reducing wound complications in complex abdominal wall
      reconstruction. MATERIALS AND METHODS: All consented patients underwent ICG-FA
      with SPY Elite after hernia repair and before flap closure. They were randomized
      into the control group, in which the surgical team was blinded to ICG-FA images
      and performed surgery as they normally would, or the experimental group, in which
      the surgery team viewed the images and could modify tissue flaps according to
      their findings. Patient variables and wound complications were compared with
      standard statistical methods. RESULTS: Among 95 patients, n = 49 control versus n
      = 46 experimental, preoperative characteristics were similar including age (58.3
      versus 56.7 y; P = 0.4), body mass index (34.9 versus 33.6 kg/m(2); P = 0.8),
      tobacco use (8.2% versus 8.7%; P = 0.9), diabetes (30.6% versus 37.0%; P = 0.5),
      and previous hernia repair (71.4% versus 60.9%; P = 0.3). Operative
      characteristics were also similar, including rate of panniculectomy (69.4% versus
      58.7%; P = 0.3) and component separation (73.5% versus 69.6%; P = 0.6). The
      experimental group more often had advancement flaps modified (37% versus 4.1%, P
      < 0.0001). There was no difference between groups in rates of skin necrosis (6.1%
      versus 2.2%; P = 0.3), fat necrosis (10.2% versus 13.0%, P = 0.7), reoperation
      (14.3% versus 26.1%, P = 0.7), wound infection (10.2% versus 21.7%; P = 0.12), or
      overall wound-related complications (32.7% versus 37.0%, P = 0.7).
      Skin/subcutaneous hypoperfusion on ICG-FA was associated with higher rates of
      wound infection (28% versus 9.4%, P < 0.02), but flap modification after viewing
      images did not prevent wound-related complications (15.6% versus 12.5%, P =
      0.99). CONCLUSIONS: This is the first randomized, double-blinded, controlled
      trial to evaluate ICG-FA in abdominal wall reconstruction. Although ICG-FA
      guidance and intraoperative modification of flaps did not prevent wound-related
      complications or reoperation, it did identify at risk patients.

PMID- 27046444
TI  - Bis-phenoxido and bis-acetato bridged heteronuclear {Co(III)Dy(III)} single
      molecule magnets with two slow relaxation branches.
AB  - Two bis-MU-phenoxido-bis-MU-acetato heterobimetallic {Co(III)Dy(III)} complexes
      and , formulated as [Co(III)Dy(III)L(MU-OAc)2(NO3)2] derived from the comparable
      hexadentate Schiff bases N,N'-ethylenebis(3-ethoxysalicylaldimine) and N,N'
      ethylenebis(3-methoxysalicylaldimine) were synthesized and X-ray structure
      analysis confirms their nearly identical structures. These are the first examples
      of bis(MU-phenoxido)-bis(MU-carboxylato) {Co(III)Dy(III)} systems. The AC
      susceptibility measurements show that both complexes exhibit a field-induced slow
      magnetic relaxation with two relaxation branches. While the high-frequency
      process spans the usual range of the relaxation time for analogous single
      molecule magnets (tau0 ~ 10(-7) s), the low-frequency branch is as slow as tau ~
      0.1 s at T = 1.9 K and B = 0.2 T.

PMID- 27046445
TI  - A Randomized Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and
      Pharmacokinetics of Trabodenoson in Healthy Adult Volunteers.
AB  - PURPOSE: To investigate the safety, tolerability, and pharmacokinetics of
      trabodenoson, a highly selective adenosine mimetic targeting the adenosine A1
      receptor. METHODS: In Part 1, 60 healthy adult volunteers were randomized to 14
      days of twice-daily topical monocular application of placebo or trabodenoson
      (200, 400, 800, 1,600, 2,400, or 3,200 MUg). In Part 2, 10 subjects were
      randomized to placebo or 8 escalating doses of bilateral trabodenoson (total
      daily doses: 1,800-6,400 MUg). RESULTS: The incidence of treatment-related
      adverse events in Part 1 was similar in the trabodenoson (27.8%) and placebo
      (25.0%) groups. Most were mild in intensity. The most common adverse events (AEs)
      for trabodenoson and placebo were headache (25.0% vs. 33%, respectively) and eye
      pain (11.1% vs. 4.2%, respectively). Ocular AEs were infrequent (16.7% and 17.9%,
      respectively), were self-limited, lasted <24 h, and were typically mild in
      intensity. The most common ocular AE was eye pain (9.5% and 3.6%, respectively),
      with a single observation of ocular hyperemia (200 MUg trabodenoson).
      Trabodenoson was rapidly absorbed [median time to maximum concentration (tmax):
      ~0.08 to 0.27 h] and eliminated (t1/2: 0.48-2.0 h), with no evidence of drug
      accumulation. Systemic exposure to topical trabodenoson was dose related but not
      dose proportional, with a plateau effect at doses >=2,400 mg per eye. No
      clinically significant treatment-related systemic AEs were observed, and
      increasing systemic exposure had no effect on heart rate or blood pressure.
      CONCLUSIONS: Ocular doses of trabodenoson up to 3,200 MUg per eye were safe and
      well tolerated in the eye and resulted in no detectable systemic effects in
      healthy adult volunteers.

PMID- 27046447
TI  - Why has under-5 mortality decreased at such different rates in different
      countries?
AB  - Controlling for socioeconomic and geographic factors, under-5 mortality (5q0) in
      developing countries has been declining at about 2.7% per year, a high rate of
      'technical progress'. This paper adduces theoretical and empirical reasons for
      rejecting the usual specification of homogeneous technical progress across
      countries and uses a panel of 95 developing countries for the period 1970-2000 to
      explore the consequences of heterogeneity. Allowing country-specific rates of
      technical progress sharply reduces the estimated income elasticity of 5q0 and
      points to country variation in technical progress as the principal source of the
      (large) cross-country variation in 5q0 decline. Education levels and physician
      coverage also contribute and are less affected than income of allowing country
      variation in technical progress. The paper concludes by decomposing 1970-2000 5q0
      decline into its different sources for each country.

PMID- 27046446
TI  - Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11
      and activating p38 which induces apoptosis of PAMs and IL-8 release.
AB  - Members of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role
      in the adhesion of Gram-negative pathogens to host cells, but the
      immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated
      that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required
      for full bacterial pathogenicity. Alveolar macrophages are the first line of
      defense against respiratory infections. This study compared the interactions
      between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b
      WT) or an Adh-deletion strain (5b DeltaAdh) via gene microarray,
      immunoprecipitation and other technologies. We found that Adh was shown to
      interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting
      in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway.
      Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling
      pathways was observed, followed by activation of caspases 8, 9, and 3. The
      immunological pathogenic roles of Adh were also confirmed in both murine and
      piglets infectious models in vivo. These results identify a novel immunological
      strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together,
      these datas reveal the high versatility of the Adh protein as a virulence factor
      and provide novel insight into the immunological pathogenic role of TAAs. 

PMID- 27046448
TI  - Epigenetic regulation of G protein coupled receptor signaling and its
      implications in psychiatric disorders.
AB  - G protein-coupled receptors (GPCRs) act as a relay center through which
      extracellular signals, in the form of neurotransmitters or therapeutics, are
      converted into an intracellular response, which ultimately shapes the overall
      response at the tissue and behavioral level. Remarkably in similar ways,
      epigenetic mechanisms also modulate the expression pattern of a large number of
      genes in response to the dynamic environment inside and outside of the body, and
      consequently overall response. Emerging evidences from the pharmacogenomics and
      preclinical studies clearly suggest that these two distinct mechanisms criss
      cross each other in several neurological disorders. At one hand such cross-talks
      between two distinct mechanisms make disease etiology more challenging to
      understand, while on the other hand if dealt appropriately, such situations might
      provide an opportunity to find novel druggable target and strategy for the
      treatment of complex diseases. In this review article, we have summarized and
      highlighted the main findings that tie epigenetic mechanisms to GPCR mediated
      signaling in the pathophysiology of central nervous system (CNS) disorders,
      including depression, addiction and pain.

PMID- 27046449
TI  - Loss of interactions between p53 and survivin gene in mesenchymal stem cells
      after spontaneous transformation in vitro.
AB  - Mesenchymal stem cells (MSC) from various animals undergo a spontaneous
      transformation in long-term culture. The transformed MSCs are highly tumorigenic
      and are likely to be the tumor-initiating cells of sarcoma. To explain why the
      transformed MSCs become tumorigenic, the present study investigated the
      characteristics of rat MSCs before and after spontaneous transformation. It was
      shown that although the transformed MSCs maintained typical surface markers of
      MSC, they exhibited some cancer stem cell-like characteristics such as loss of
      contact inhibition and multi-potency to mesenchymal lineages, and acquirement of
      ability of anchorage-independent growth. The expression of a key senescence
      regulator p16 almost disappeared, but the other one, p53 abnormally increased in
      the transformed MSCs. ChIP assay demonstrated that a normal negative regulation
      of p53 on survivin gene disappeared in the transformed cells due to a lack of p53
      binding to the promoter of survivin gene. DNA sequencing revealed that the p53
      gene in transformed MSCs was not a wild-type, but a 942C>T mutant with the
      mutation located in the sequence coding p53 protein's DNA-binding domain. These
      findings indicate that the transformed MSCs express high levels of a p53 mutant
      that loses the ability to bind survivin gene, leading to an abnormally
      upregulated expression of survivin, which is a key reason for the cell's
      unlimited proliferation.

PMID- 27046450
TI  - Family Rejection as a Predictor of Suicide Attempts and Substance Misuse Among
      Transgender and Gender Nonconforming Adults.
AB  - PURPOSE: We examined associations between family rejection and risk of suicide
      attempts and substance misuse among a national sample of transgender and gender
      nonconforming adults. METHODS: Data were drawn from the National Transgender
      Discrimination Survey (N = 6456). This secondary analysis was restricted to 3458
      individuals who self-identified as transgender or gender nonconforming and
      provided complete data on study variables. We used multivariable logistic
      regression to examine health risks by level of reported family rejection
      (low/moderate/high), controlling for relevant sociodemographic characteristics.
      RESULTS: Overall, 42.3% of the sample reported a suicide attempt and 26.3%
      reported misusing drugs or alcohol to cope with transgender-related
      discrimination. After controlling for age, race/ethnicity, sex assigned at birth,
      binary gender identity, income, education, and employment status, family
      rejection was associated with increased odds of both behaviors. Odds increased
      significantly with increasing levels of family rejection. CONCLUSIONS: Family
      rejection related to gender identity is an understudied interpersonal stressor
      that may negatively affect health outcomes for transgender and gender
      nonconforming individuals. A better understanding of the role of close
      relationships in both risk and resilience for transgender individuals is critical
      in the development of effective public health interventions for this community.

PMID- 27046451
TI  - On the origin and nature of the grating interferometric dark-field contrast
      obtained with low-brilliance x-ray sources.
AB  - The x-ray dark-field contrast accessible via grating interferometry is sensitive
      to features at length scales well below what is resolvable by a detector system.
      It is commonly explained as arising from small-angle x-ray scattering (SAXS), and
      can be implemented both at synchrotron beamlines and with low-brilliance sources
      such as x-ray tubes. Here, we demonstrate that for tube based setups the
      underlying process of image formation can be fundamentally different. For focal
      spots or detector pixels that comprise multiple grating periods, we show that
      dark-field images contain a strong artificial and system-specific component not
      arising from SAXS. Based on experiments carried out with a nanofocus x-ray tube
      and the example of an excised rat lung, we demonstrate that the dark-field
      contrast observed for porous media transforms into a differential phase contrast
      for large geometric magnifications. Using a photon counting detector with an
      adjustable point spread function, we confirm that a dark-field image can indeed
      be formed by an intra-pixel differential phase contrast that cannot be resolved
      as such due to a dephasing between the periodicities of the absorption grating
      and the Talbot carpet. Our findings are further corroborated by a link between
      the strength of this pseudo-dark-field contrast and our x-ray tube's focal spot
      size in a three-grating setup. These results must not be ignored when
      measurements are intended to be reproducible across systems. 

PMID- 27046452
TI  - Oral vaccination against plague using Yersinia pseudotuberculosis.
AB  - Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens
      affecting humans, and is a potential biological weapon. Because antibiotic
      resistant strains of Yersinia pestis have been observed or could be engineered
      for evil use, vaccination against plague might become the only means to reduce
      mortality. Although plague is re-emerging in many countries, a vaccine with
      worldwide license is currently lacking. The vaccine strategy described here is
      based on an oral vaccination with an attenuated strain of Yersinia
      pseudotuberculosis. Indeed, this species is genetically almost identical to Y.
      pestis, but has a much lower pathogenicity and a higher genomic stability.
      Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953
      were performed to generate a safe and immunogenic vaccine. Genes coding for three
      essential virulence factors were deleted from this strain. To increase cross
      species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then
      generated. For this, the Y. pestis caf operon, which encodes F1, was inserted
      first on a plasmid, and subsequently into the chromosome. The successive steps
      achieved to reach maximal vaccine potential are described, and how each step
      affected bacterial virulence and the development of a protective immune response
      is discussed. The final version of the vaccine, named VTnF1, provides a highly
      efficient and long-lasting protection against both bubonic and pneumonic plague
      after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist
      or could be engineered, we also analyzed the protection conferred by the vaccine
      against such strain and found that it also confers full protection against the
      two forms of plague. Thus, the properties of VTnF1 makes it one of the most
      efficient candidate vaccine for mass vaccination in tropical endemic areas as
      well as for populations exposed to bioterrorism.

PMID- 27046453
TI  - Effect of latissimus dorsi flap breast reconstruction on the strength profile of
      the upper extremity.
AB  - OBJECTIVE: Dissection of the latissimus dorsi (LD) flap may have a distinct
      impact on upper extremity function and strength. To date, insufficient
      differentiation has been made between loss of muscular strength and shoulder
      function by dissection of the LD muscle per se and loss of function resulting
      from all excisional surgery, radiation therapy, and reconstructive procedures at
      the donor site and the recipient site that may have been combined near the
      shoulder region. METHODS: This study determines the long-term effect of the LD
      breast reconstruction on the strength profiles of the upper extremity by
      measuring the isometric torque strength both in seven synergistic- and two contra
      movement directions. The Biodex System 3 Pro (Biodex Medical Systems, New York,
      NY) was used in 12 patients at a mean of 3.5 years after surgery, and in 20
      matched controls. Because loss of LD muscle may not result in significant
      impairment of activities of daily live (ADL) even in cases where objective
      measurements are decreased, this study simultaneously assessed the subjective
      function by use of the standardised Disability of Arm, Shoulder and Hand (DASH)
      questionnaire. RESULTS: This study observed a significant long-term loss of 8.8
      Nm or 19% LD torque strength in synergistic movement directions after
      transplantation of the LD muscle. This loss correlated significantly with an
      increase of the mean DASH score among the patients. CONCLUSIONS: Because no
      significant loss of contra-movement torque strength was observed, it was
      concluded that the loss of synergistic torque strength appears to result from the
      loss of LD function per se.

PMID- 27046454
TI  - Escalation of intravenous self-administration of methylone and mephedrone under
      extended access conditions.
AB  - The recreational use of substituted cathinones continues to grow as a public
      health concern in the United States. Studies have shown that extended access to
      intravenous (i.v.) self-administration of stimulants, such as cocaine and
      methamphetamine, results in escalation of drug intake relative to shorter access;
      however, little is known about the impact of extended access on self
      administration of entactogen class stimulants such as methylone and 4
      methylmethcathinone (mephedrone). Male Wistar rats were randomly assigned to
      short-access (ShA, 2- h) and long-access (LgA, 6- h) groups and trained to self
      administer methylone or mephedrone (0.5 mg/kg/infusion) using a fixed-ratio 1
      response contingency. The methylone-trained groups were evaluated on a
      progressive-ratio (PR) procedure incorporating dose-substitution of methylone
      (0.125-2.5 mg/kg/infusion), mephedrone (0.125-2.5 mg/kg/infusion) or
      methamphetamine (MA; 0.01-0.5 mg/kg/infusion). Mephedrone-trained rats were
      similarly evaluated on a PR with mephedrone and MA. Rats trained with LgA to
      methylone and mephedrone earned more infusions during acquisition compared with
      ShA groups. Mephedrone-trained LgA rats reached significantly higher breakpoints
      than all other groups in mephedrone and MA PR tests. Methylone-trained LgA rats
      exhibited a rightward shift of the peak effective dose but no overall efficacy
      change compared with methylone-trained ShA rats. These findings show that the
      self-administration of mephedrone escalates under LgA conditions in a manner
      similar to traditional stimulants whereas escalation of 6 h intakes of methylone
      is not accompanied by differences in PR performance. Thus mephedrone represents
      the greater risk for dysregulated drug consumption.

PMID- 27046455
TI  - Diagnostic and Therapeutic Challenges.

PMID- 27046456
TI  - CHOROIDAL THICKNESS CHANGES IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH
      PANRETINAL PHOTOCOAGULATION VERSUS PANRETINAL PHOTOCOAGULATION WITH INTRAVITREAL
      BEVACIZUMAB.
AB  - PURPOSE: To compare choroidal thickness (CT) and retinal thickness (RT) between
      eyes with proliferative diabetic retinopathy treated with panretinal
      photocoagulation (PRP) or PRP with intravitreal bevacizumab (PRP + IVB). METHODS:
      Thirty-three patients with proliferative diabetic retinopathy were randomized to
      have one eye treated with PRP and the other with PRP + IVB. Change in CT was
      compared with baseline using enhanced depth imaging-optical coherence tomography
      at baseline and Months 1, 3, 6, and 10 after treatment. Change in RT was
      similarly assessed using spectral domain optical coherence tomography. Changes in
      both CT and RT were assessed in all nine macular areas as defined by Early
      Treatment Diabetic Retinopathy Study subfields. RESULTS: The PRP + IVB group had
      a significant decrease in subfoveal CT at 3 and 10 months (323.9 +/- 62 MUm at
      baseline vs. 320.7 +/- 64.8 MUm at Month 3 [P = 0.024] and 304.7 +/- 65.6 MUm at
      Month 10 [P = 0.003]). Subfoveal CT significantly decreased at 10 months compared
      with baseline in the PRP group (320.8 +/- 57.7 at baseline to 297 +/- 66.3 MUm at
      10 months, P = 0.01). Subfoveal CT was not significantly different between the 2
      groups at 10 months. The best-corrected visual acuity did not change after
      treatment in the two groups, and there was no correlation between BCVA and CT
      changes (r = 0.222, P = 0.37 in the PRP group and r = 0.387, P = 0.12 in the PRP
      + IVB group). Significant increases in RT were seen in the PRP + IVB group at 6
      months and in the PRP group at Months 1, 3, 6, and 10. A correlation between
      changes in CT and RT was only seen in the PRP group at 10 months after treatment.
      CONCLUSION: Eyes with proliferative diabetic retinopathy treated with PRP + IVB
      and PRP both had significant reduction in CT at 10 months; however, the eyes that
      were also treated with IVB also underwent an earlier but transient reduction at 3
      months. Patients treated with IVB underwent less increase in RT.

PMID- 27046457
TI  - EXPERIMENTAL VISUALIZATION AND QUANTIFICATION OF VITREOUS CONTAMINATION FOLLOWING
      INTRAVITREAL INJECTIONS.
AB  - PURPOSE: To detect and quantify vitreous contamination after intravitreal
      injection using an experimental vitreous contamination model. METHODS: Enucleated
      porcine eyes served as a Type 1 experimental vitreous contamination model with
      fluoresbrite carboxylate microspheres applied to the conjunctival surface. Saline
      solution (0.05 mL) was injected using a 27-, 30-, or 32-gauge (G) needle.
      Injection procedures were monitored using an intraocular fiber catheter.
      Condensed microspheres were applied to an excised sheet of porcine sclera (Type 2
      experimental vitreous contamination model). Saline solution (0.05 mL) was
      injected from the top of an applied condensed microsphere through the sclera
      using a needle of one of the aforementioned gauges, and samples were then
      collected. The fluorescence strength of samples was measured using
      fluorophotometry. RESULTS: We visually detected fluorescent microspheres in
      10/10, 9/10, and 9/10 eyes injected with 27-G, 30-G, and 32-G needles,
      respectively. In the experimental quantification study, values at all needle
      gauges were significantly higher than those of controls (P < 0.01). Fluorescence
      strength was significantly higher in the 27-G group than in the 30- (P < 0.01)
      and 32-G (P < 0.01) groups. CONCLUSION: Intravitreal injection carries the risk
      of introducing contamination directly into the eyes even when a 32-G needle is
      used. Furthermore, the 27-G needle carries the highest contamination risk.

PMID- 27046458
TI  - NONSUPINE POSITIONING IN MACULAR HOLE SURGERY: A Noninferiority Randomized
      Clinical Trial.
AB  - PURPOSE: To determine whether nonsupine positioning (NSP) is noninferior to face
      down positioning (FDP) in full-thickness macular hole (FTMH) surgery. METHODS:
      This is a single-center, open-label, randomized controlled trial. Between October
      2013 and October 2014, pseudophakic participants underwent pars plana vitrectomy,
      internal limiting membrane peeling, and perfluoropropane gas tamponade and were
      randomly allocated to either FDP or NSP. The primary (noninferior) outcome was
      FTMH closure. The sample size was based on an estimated 95% closure rate and a 
      15% noninferiority margin for the NSP group. The secondary outcome was Early
      Treatment Diabetic Retinopathy Study visual acuity at 3 months. Additionally,
      intraocular gas fill on postoperative Day 4 was measured. RESULTS: Eighty-one
      participants were enrolled. Final analysis of 68 participants demonstrated equal
      closure rates in both positioning groups: 33/34 (97.1%; 95% confidence interval:
      84.7-99.9). Closure rates in the >=400-MUm FTMH subgroup were similar, 93.8% and
      100.0% in the FDP and NSP groups, respectively (P = 0.43). Final visual acuity
      did not differ significantly between the groups (P = 0.60). Median gas fill was
      78% (range: 57-86) in the FDP group and 76% (range: 56-85) in the NSP group (P =
      0.51). Gas fill in closed FTMHs was significantly higher than in unclosed FTMHs
      (P = 0.02). CONCLUSION: Nonsupine positioning is noninferior to FDP in FTMH
      surgery. Furthermore, results suggest that the degree of gas fill affects FTMH
      closure.

PMID- 27046459
TI  - Curindolizine, an Anti-Inflammatory Agent Assembled via Michael Addition of
      Pyrrole Alkaloids Inside Fungal Cells.
AB  - Curvularia sp. IFB-Z10, a white croaker-associated fungus, generates a skeletally
      unprecedented indolizine alkaloid named curindolizine (1), which displays an anti
      inflammatory action in lipopolyssacharide (LPS)-induced RAW 264.7 macrophages
      with an IC50 value of 5.31 +/- 0.21 MUM. The enzymatic transformation test
      demonstrated that the unique curindolizine architecture was most likely produced
      by the regiospecific in-cell Michael addition reaction between pyrrole alkaloids,
      curvulamine, and 3,5-dimethylindolizin-8(5H)-one. 

PMID- 27046460
TI  - Graphene-Templated Synthesis of Magnetic Metal Organic Framework Nanocomposites
      for Selective Enrichment of Biomolecules.
AB  - Successful control of homogeneous and complete coating of graphene or graphene
      based composites with well-defined metal organic framework (MOF) layers is a
      great challenge. Herein, novel magnetic graphene MOF composites were constructed
      via a simple strategy for self-assembly of well-distributed, dense, and highly
      porous MOFs on both sides of graphene nanosheets. Graphene functionalized with
      magnetic nanoparticles and carboxylic groups on both sides was explored as the
      backbone and template to direct the controllable self-assembly of MOFs. The
      prepared composite materials have a relatively high specific surface area (345.4
      m(2) g(-1)), and their average pore size is measured to be 3.2 nm. Their
      relatively high saturation magnetization (23.8 emu g(-1)) indicates their strong
      magnetism at room temperature. Moreover, the multifunctional composite was
      demonstrated to be a highly effective affinity material in selective extraction
      and separation of low-concentration biomolecules from biological samples, in
      virtue of the size-selection property of the unique porous structure and the
      excellent affinity of the composite materials. Besides providing a solution for
      the construction of well-defined functional graphene-based MOFs, this work could
      also contribute to selective extraction of biomolecules, in virtue of the
      universal affinity between immobilized metal ions and biomolecules.

PMID- 27046461
TI  - Effects of different doses of tramadol added to levobupivacaine in continuous
      wound infusion for postoperative pain treatment following cesarean section.
AB  - OBJECTIVE: The aim of this study was to compare the effects of two different
      doses of tramadol added to levobupivacaine as continuous wound infusion, on VAS
      scores following cesarean section. METHODS: The study was conducted in an
      University Hospital and was approved by the Local Ethical Committee. Sixty-five
      ASA I-II parturients, between 18 and 45 years were enrolled. The participants
      were randomized to three groups. Group T1 (n = 21) was given the study solution
      consisting of levobupivacaine 0.25% + tramadol 1 mg/kg. Group T2 (n = 21) was
      given levobupivacaine 0.25% + tramadol 2 mg/kg and Group L (n = 21) was given
      levobupivacaine 0.25%, subcutaneously, alone. Each patient who delivered by
      cesarean section was applied a triple orifice epidural catheter above rectus
      fascia for continious wound infiltration. VAS at rest and with 20 degrees leg
      lift, time to first additional analgesic, total additional analgesic consumption,
      side effects, and sedation scores were recorded. RESULTS: There were no
      statistically significant differences among groups, concerning VAS scores at rest
      and VAS scores at leg lift. Total amount of additional analgesics and sedation
      scores were also similar for three groups. CONCLUSION: Different doses of
      tramadol as adjunct to local anesthetics in continuous wound infiltration
      following cesarean section do not seem to provide superior analgesia.

PMID- 27046462
TI  - Protonation of carbene-stabilized diphosphorus: complexation of HP2(+).
AB  - Reaction of carbene-stabilized diphosphorus, L:P-P:L (5) (L: = :C{N(2,6
      Pr(i)2C6H3)CH}2) with pyridine hydrochloride yields [L:(H)P-P:L]Cl (6), a salt
      containing the HP2(+) cation--the elusive phosphorus analogue of the well known
      diazonium cation, HN2(+). In addition to reporting the synthesis and structure,
      the nature of (6) was further probed by DFT computations. Interestingly, carbenes
      may be employed to deprotonate (6), affording the starting material (5).

PMID- 27046463
TI  - Lineage-specific STAT5 target gene activation in hematopoietic progenitor cells
      predicts the FLT3(+)-mediated leukemic phenotype.
AB  - Mutations that activate FMS-like tyrosine kinase 3 (FLT3) are frequent
      occurrences in acute myeloid leukemia. Two distinct types of mutations have been
      described: internal duplication of the juxtamembranous domain (ITD) and point
      mutations of the tyrosine kinase domain (TKD). Although both mutations lead to
      constitutive FLT3 signaling, only FLT3-ITD strongly activates signal transducer
      and activator of transcription 5 (STAT5). In a murine transplantation model, FLT3
      ITD induces a myeloproliferative neoplasm, whereas FLT3-TKD leads to a lymphoid
      malignancy with significantly longer latency. Here we report that the presence of
      STAT5 is critical for the development of a myeloproliferative disease by FLT3-ITD
      in mice. Deletion of Stat5 in FLT3-ITD-induced leukemogenesis leads not only to a
      significantly longer survival (82 vs 27 days) of the diseased mice, but also to
      an immunophenotype switch with expansion of the lymphoid cell compartment.
      Interestingly, we were able to show differential STAT5 activation in FLT3-ITD(+)
      myeloid and lymphoid murine progenitors. STAT5 target genes such as Oncostatin M
      were highly expressed in FLT3-ITD(+) myeloid but not in FLT3-ITD(+) lymphoid
      progenitor cells. Strikingly, FLT3-TKD expression in combination with Oncostatin
      M is sufficient to reverse the phenotype to a myeloproliferative disease in FLT3
      TKD mice. Thus, lineage-specific STAT5 activation in hematopoietic progenitor
      cells predicts the FLT3(+)-mediated leukemic phenotype in mice.

PMID- 27046464
TI  - Pincer Flap for Reconstruction of Nasal Tip Defects.
AB  - INTRODUCTION: Reconstruction of the nasal tip defects is challenging because of
      variable contours of the region and the unique texture, thickness, color, and
      limited amount of available skin. There are several well-known local flaps for
      this purpose. Unfortunately, most of these flaps are suitable for small sized
      defects up to 2 cm in diameter. In this study, the authors are presenting a new
      flap for reconstruction of nasal tip and supratip defects larger than 2 cm in
      diameter. METHODS: Pincer flap was used for reconstruction of nasal tip defects
      in 12 patients, between 2011 and 2014. The mean age was 67 (43-88). All patients
      had a basal cell carcinoma. Defects were located at the central nasal, lateral
      nasal, and supratip areas. All tumors were excised with safe margins. After the
      excision, defects were reconstructed with pincer flap in the same session.
      RESULTS: The mean follow-up period was 11 (6-18) months. There was not any flap
      loss. Infection and venous congestion was observed in 2 patients but the patient
      did not require any further surgical intervention, and healed with local and
      systemic antibiotherapy. No recurrence occurred and the outcome was aesthetically
      favorable. CONCLUSIONS: The authors concluded that pincer flap is reliable and
      may provide a single-stage reconstruction for the nasal tip defects larger than 2
      cm and up to 3 cm in diameter.

PMID- 27046465
TI  - Iliolumbar Vein as a Training Model for Microsurgical End-to-Side Anastomosis.
AB  - Although a multitude of microsurgical training models have been reported, few
      experimental animal models are available for end-to-side anastomosis. In this
      study, the authors developed an end-to-side anastomosis rat training model that
      utilizes the iliolumbar vein and investigated its characteristics. Ten Wistar
      male rats were used as microvascular end-to-side anastomosis models. Diameters of
      the posterior vena cava and the root of the iliolumbar vein were measured on both
      sides. The mean diameter of the posterior vena cava was 5.40 mm (range, 3.2-3.6
      mm). The mean diameter of the root of the iliolumbar vein was 1.12 mm (range, 1.1
      1.4 mm). The mean duration of bilateral end-to-side anastomosis was 50.6 minutes
      (range, 48-55 minutes). The intraoperative patency rate after anastomosis was
      100%. The authors described a rat training model for microsurgical end-to-side
      anastomosis. This model is especially useful because it closely simulates a real
      operation, and training can be performed relatively quickly. 

PMID- 27046466
TI  - Surgical Treatment Outcomes of Head and Neck Lymphatic Malformations in Patients
      With a Variety of Ages and Unusual Sites.
AB  - OBJECTIVE: The objective of this study was to review the clinical characteristics
      and surgical treatment outcomes of head and neck lymphatic malformations and to
      define the risk factors for recurrence. METHODS: A retrospective chart review was
      performed at Chonnam National University Hwasun Hospital from January 2010 to
      February 2015. RESULTS: The unusual sites for a head and neck lymphatic
      malformation were tonsil, buccal space, nasopharynx, and the vallecula. No
      recurrence of lymphatic malformations was observed when the lesion was removed
      completely. Recurrence was more common in patients with the infiltrative type and
      incomplete excision. CONCLUSIONS: Lymphatic malformations occurred in patients
      with a variety of ages and unusual sites. Surgical excision could become the
      treatment of choice if the malformation can be excised completely without serious
      complications. Recurrence was more common in patients in whom an infiltrative
      type malformation was incomplete excised.

PMID- 27046467
TI  - Delayed Facial Palsy After Microvascular Decompression for Hemifacial Spasm.
AB  - The purpose of this article is to study the etiology, treatment, and prognosis of
      delayed facial palsy (DFP) after microvascular decompression (MVD) for the
      hemifacial spasm. Between January 2012 and January 2014, 562 patients who
      underwent MVD for hemifacial spasm at our institution were retrospectively
      studied. Among 562 patients, 34 patients developed DFP after MVD with an
      incidence of 6%. The duration of palsy was 15 to 136 days (average 51.2 days).
      There was statistical relevance between preoperative duration of the course, the
      facial nerve for indentation, and the incidence of delayed facial paralysis. All
      the symptoms of facial paralysis were obviously improved. DFP is not an unusual
      complication after MVD, and prognosis is fairly good. 

PMID- 27046468
TI  - Three-Dimensional Finite Element Analysis Surface Stress Distribution on Regular
      and Short Morse Taper Implants Generated by Splinted and Nonsplinted Prostheses
      in the Rehabilitation of Various Bony Ridges.
AB  - AIMS: This study used finite element analysis to compare the biomechanical
      performance of splinted (SP) and nonsplinted (NSP) prostheses to regular and
      short length Morse taper implants in the posterior side of the mandible. METHODS:
      The authors used 3-dimensional geometric models of regular implants (?4 * 11 mm)
      and short implants (?4 * 5 mm) housed in the corresponding bone edges of the
      posterior left mandibular hemiarch involving tooth 34. The 8 experimental groups
      were: the control group SP (3 regular implants rehabilitated with SP), group 1SP
      (2 regular and 1 short implants rehabilitated with SP), group 2SP (1 regular and
      2 short implants rehabilitated with SP), group 3SP (3 short implants
      rehabilitated with SP), the control group NSP (3 regular implants rehabilitated
      with NSP), group 1NSP (2 and 1 short implants rehabilitated with NSP), group 2NSP
      (1 regular and 2 short implants rehabilitated with NSP), and group 3NSP (3 short
      implants rehabilitated with NSP). Oblique forces were simulated in the molars
      (365 N) and premolars (200 N). Qualitative and quantitative analysis of the
      distribution of Von Mises equivalent stress (implants, components, and
      infrastructure) was performed using the AnsysWorkbench10.0 software. RESULTS AND
      CONCLUSIONS: The results showed that the use of SP provides several advantages
      and benefits, reducing the stresses placed on the implant surface, on the
      transmucosal abutment areas and on the interior region of the infrastructure. The
      use of NSP was advantageous in reducing the stresses on the abutments and in the
      distal interproximal area of connection between the crowns.

PMID- 27046469
TI  - Therapeutic Effects of Sildenafil on Experimental Mandibular Fractures.
AB  - OBJECTIVES: No previous studies have examined the effect of sildenafil on
      fracture healing. This study was designed to investigate the effect of sildenafil
      on the fracture healing process. METHODS: Thirty-six female Sprague-Dawley rats
      (3-month-old) were used in this study. Animals were randomly divided into 2
      groups based on treatment duration (1 week versus 4 weeks) and each group was
      then divided further into 2 subgroups, control (C) and study (S) groups. Group C
      (C1, C2) was treated daily with saline solution and group S (S1, S2) was treated
      daily with 10 mg/kg of sildenafil. Histologic, histomorphometric, radiological,
      and immunohistochemical analyses were performed at 1 week and 4 weeks after a
      fracture. RESULTS: The sildenafil group showed a significant increase in fracture
      healing scores (P = 0.00). The authors observed a transition from fibrous callus
      to cartilage tissue and immature bone tissue in group S1; and an increased
      transition of cartilage tissue to completely immature bone tissue in group S2,
      both of which were administered sildenafil. The strong expression of bone
      morphogenetic protein 2 and col-1 was observed in the fibrous matrix and
      osteoblasts within areas of new bone formation, especially in group S1. This
      group also showed an increase in bone density measurements at 1 week that was
      statistically significant (P = 0.03). CONCLUSIONS: Sildenafil accelerates
      fracture healing and can be used as a supporting factor in the improvement of
      fracture healing under various conditions.

PMID- 27046470
TI  - Pediatric National Surgical Quality Improvement Program: Useful for Quality
      Improvement in Craniosynostosis Surgery?
AB  - The American College of Surgeons and the American Pediatric Surgical Association
      collaborate to provide pediatric hospitals with multispeciality surgical outcomes
      data through the Pediatric National Surgical Quality Improvement Program (NSQIP
      Peds). The authors used this national multicenter database to describe 30-day
      outcomes from craniosynostosis surgery and identify associations with
      perioperative events and blood transfusion.Data from NSQIP Peds were used to
      describe children undergoing craniosynostosis surgery. The authors examined
      statistical association of clinical risk factors with the defined end point
      outcomes of perioperative complications and blood transfusion.Five hundred
      seventy-two surgeries were included. By Common Procedural Terminology codes, 93
      identified as single suture synostosis, the remainder as multiple or unknown
      suture involvement. Location of the affected suture is not captured. Mean
      surgical time was 196.84 minutes (SD 113.46). Mean length of stay was 4.22 days
      (SD 5.04). Sixty-seven percent of patients received blood transfusions. 3.15%
      were other perioperative occurrences, including infection, wound disruption,
      unplanned reintubation, stroke/hemorrhage, cardiac arrest, seizures,
      thromboembolism. 2.8% were readmitted; 2.45% underwent reoperation within 30
      days. Duration of surgery and length of hospital stay significantly differed in
      the presence of blood transfusion versus none. On multivariate analysis, duration
      from anesthesia start to surgery start, duration from surgery end to anesthesia
      end, and duration of operation were risk factors for blood transfusion.Pediatric
      NSQIP gives a national overview of 30-day outcome metrics in craniosynostosis
      surgery. Perioperative adverse event rate was 3.15%. Duration of surgery and
      duration of anesthesia were significantly associated with blood transfusion. The
      authors identified opportunities for pediatric NSQIP database improvement. 

PMID- 27046471
TI  - Maxillary Sinus Floor Elevation Using Platelet-Rich Plasma Combined With Either
      Biphasic Calcium Phosphate or Deproteinized Bovine Bone.
AB  - PURPOSE: Maxillary sinus floor elevation procedure has the objective of
      augmenting available bone in atrophic posterior maxilla to allow dental implants
      placement. The main aim of this prospective study was to evaluate clinically and
      histomorphometrically the performance of biphasic calcium phosphate (BCP) used in
      conjunction with platelet-rich plasma (PRP) compared with demineralized bovine
      bone matrix (DBBM) and PRP in sinus floor elevation surgery. MATERIALS AND
      METHODS: Patients candidate to sinus floor elevation were treated using either
      BCP and PRP or DBBM and PRP. Biopsies were retrieved using trephine bur during
      implant placement surgery 6 months after grafting. Clinical success of implants
      was evaluated 1 year after prosthesis delivery. Histomorphometric analysis was
      performed assessing the relative volume of newly formed bone. RESULTS: A total of
      20 patients were recruited, and 20 sinus augmentation procedures were performed,
      10 for each group. A total of 42 implants were placed. One year after prosthetic
      loading a 100% implant survival rate was reported in both groups.
      Histomorphometric analysis revealed that the mean amount of new bone formation
      was 18.6 +/- 3.3% in BCP group and it was 21.9 +/- 4.9% in DBBM group, without
      statistically significant difference. In BCP group a greater amount of collagen
      type I was found with respect to DBBM group. CONCLUSIONS: Both grafting materials
      led to an excellent performance regarding implant survival rate after 1 year
      follow-up, without any significant adverse sequelae. A similar capability of
      inducing new bone formation was observed in both groups, even though the higher
      quantity of collagen type I in BCP group may suggest a greater potential for bone
      formation over time as compared with DBBM.

PMID- 27046472
TI  - Adjunctive Effect of Autologus Platelet-Rich Fibrin to Barrier Membrane in the
      Treatment of Periodontal Intrabony Defects.
AB  - BACKGROUND AND AIM: Autologous platelet-rich fibrin (PRF) and barrier membranes
      in the treatment of intrabony defects in chronic periodontitis patients have
      shown significant clinical benefits. This study evaluates the additive effect of
      autologous PRF in combination with a barrier membrane versus the use of barrier
      membrane alone for the treatment of intrabony defects in chronic periodontitis
      patients. METHODS: A randomized split-mouth design was used. Sixteen patients
      with 32 paired intrabony defects were included. In each patient 1 defect was
      treated using a resorbable collagen membrane along with PRF (test group) and the
      other defect by guided tissue regeneration alone (control group). The following
      clinical parameters were measured at baseline and after 9 months: plaque index,
      modified sulcus bleeding index, probing pocket depth, clinical attachment level,
      and gingival marginal level. The radiographic defect depth was also assessed at
      baseline and after 9 months. RESULTS: Test group showed a statistically
      significant improvement for probing depth (P = 0.002), clinical attachment level
      (P = 0.001), and radiographic defect depth (P < 0.001) after 9 months as compared
      with the control sites. Radiographic defect depth reduction was 58.19 +/- 13.24%
      in the test group as compared with 24.86 +/- 9.94% reduction in the control
      group. CONCLUSIONS: The adjunctive use of PRF in combination with barrier
      membrane is more effective in the treatment of intrabony defects in chronic
      periodontitis as compared with barrier membrane alone.

PMID- 27046473
TI  - In the Heart of the Sea: How to Get a Motif?

PMID- 27046474
TI  - Reverse genetics in high throughput: rapid generation of complete negative strand
      RNA virus cDNA clones and recombinant viruses thereof.
AB  - Reverse genetics approaches are indispensable tools for proof of concepts in
      virus replication and pathogenesis. For negative strand RNA viruses (NSVs) the
      limited number of infectious cDNA clones represents a bottleneck as clones are
      often generated from cell culture adapted or attenuated viruses, with limited
      potential for pathogenesis research. We developed a system in which cDNA copies
      of complete NSV genomes were directly cloned into reverse genetics vectors by
      linear-to-linear RedE/T recombination. Rapid cloning of multiple rabies virus
      (RABV) full length genomes and identification of clones identical to field virus
      consensus sequence confirmed the approache's reliability. Recombinant viruses
      were recovered from field virus cDNA clones. Similar growth kinetics of parental
      and recombinant viruses, preservation of field virus characters in cell type
      specific replication and virulence in the mouse model were confirmed. Reduced
      titers after reporter gene insertion indicated that the low level of field virus
      replication is affected by gene insertions. The flexibility of the strategy was
      demonstrated by cloning multiple copies of an orthobunyavirus L genome segment.
      This important step in reverse genetics technology development opens novel
      avenues for the analysis of virus variability combined with phenotypical
      characterization of recombinant viruses at a clonal level. 

PMID- 27046475
TI  - Medical mistrust among social network members may contribute to antiretroviral
      treatment nonadherence in African Americans living with HIV.
AB  - RATIONALE: African Americans living with HIV are less likely to adhere to
      antiretroviral treatment (ART) compared to other racial/ethnic groups. Medical
      mistrust is thought to be a factor in this disparity. OBJECTIVE: We examined (1)
      whether exposure to HIV conspiracy beliefs, a specific type of HIV-related
      mistrust (about the origins and treatment of HIV) in social networks is
      associated with ART nonadherence among African Americans living with HIV; and (2)
      the characteristics of individuals who discuss HIV-related mistrust in the social
      networks of African Americans living with HIV. METHODS: At baseline and 6- and 12
      months post-baseline, 175 African Americans living with HIV on ART completed
      egocentric social network assessments, from which we assessed the structure and
      composition of their personal networks (the social context immediately
      surrounding them). HIV-related mistrust was operationalized with an indicator of
      whether any social network member had expressed HIV conspiracy beliefs to the
      participant. Daily medication adherence was monitored electronically. RESULTS: At
      baseline, 63% of participants agreed with at least one conspiracy belief, and 55%
      reported hearing at least one social network member ("alter") express conspiracy
      beliefs. In a multivariate linear repeated measures regression, expression of
      conspiracy beliefs by similar others in the network (in terms of age, gender, HIV
      status, sexual orientation, and race/ethnicity) was associated with ART
      nonadherence (i.e., percentage of prescribed doses taken). In a multivariate
      logistic regression, expression of conspiracy beliefs was more likely among
      social network members who were HIV-positive, who knew the participants'
      serostatus, and with whom participants interacted frequently, and less likely
      among more well-connected social network members. CONCLUSION: HIV-related
      mistrust in the network may be most influential when expressed by similar others
      who may be HIV-positive themselves.

PMID- 27046479
TI  - The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on
      mineral metabolism and bone in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors lower blood
      glucose levels in patients with type 2 diabetes mellitus (T2DM) by increasing
      urinary glucose excretion. This review provides a comprehensive summary of
      preclinical and clinical data on the effects of the SGLT2 inhibitor canagliflozin
      on mineral balance and bone. METHODS: Published articles and internal study
      reports through November 2015 were included. RESULTS: In clinical studies,
      canagliflozin was not associated with meaningful changes in serum or urine
      calcium, parathyroid hormone, or vitamin D. Canagliflozin was associated with
      increases in serum magnesium and phosphate without changes in their urinary
      excretion. Increases in serum collagen type-1 beta-carboxy-telopeptide (beta
      CTX), a bone resorption marker, and osteocalcin, a bone formation marker, were
      observed with canagliflozin. Decreases in total hip bone mineral density (BMD) of
      up to 1.2% were seen with canagliflozin after 2 years; no changes in BMD were
      seen at other skeletal sites. Changes in total hip BMD and serum beta-CTX with
      canagliflozin correlated with decreases in body weight. In a clinical program
      wide analysis, canagliflozin was associated with increased fracture risk that was
      driven by a higher incidence in the cardiovascular safety study (CANVAS), with no
      fracture imbalance seen in pooled data from other Phase 3 studies. The fracture
      imbalance occurred within 12 weeks after initiating treatment, most frequently in
      the distal portion of the upper and lower extremities. CONCLUSIONS: Across
      clinical studies, canagliflozin did not meaningfully affect calcium homeostasis
      or hormones regulating calcium homeostasis. Increases in bone turnover markers
      and decreases in BMD at the total hip, but not at other sites, that correlated
      with weight loss were seen with canagliflozin. Canagliflozin was associated with
      a higher fracture incidence within 12 weeks, primarily in distal extremities.
      Data from ongoing canagliflozin studies will provide additional information on
      fracture risk.

PMID- 27046480
TI  - Impact of stress on Aeromonas diversity in tambaqui (Colossoma macropomum) and
      lectin level change towards a bacterial challenge.
AB  - Tambaqui (Colossoma macropomum) is among the most cultivated fish species in
      tropical countries. Stress is the main cause of disease in fish farms. The genus
      Aeromonas is a common causative agent of fish diseases. This work reports the
      identification of Aeromonas species colonizing gills of C. macropomum submitted
      or not to a confinement stress. We also evaluated changes in serum levels of
      lectins (carbohydrate-binding proteins that are components of fish immune system)
      in tambaqui submitted to a challenge using two isolated Aeromonas strains. Gill
      tissues from stressed and unstressed fishes were used to isolate Aeromonas. Then
      72 Aeromonas strains were isolated, 97% being from stressed fishes. Among these,
      63 were identified at species level and 6 were classified as atypical Aeromonas
      strains. The most prevalent species were Aeromonas bestiarum and Aeromonas caviae
      and their strains were used in bacterial challenges. The lectin serum levels
      significantly increased after 24 h of infection with A. bestiarum; however, no
      significant increase was found for infection with A. caviae. In conclusion, C.
      macropomum gills are susceptible to colonization by different Aeromonas species,
      mainly at confinement stressful conditions, and serum lectins may have a role in
      the acute immunological response towards infection by A. bestiarum. 

PMID- 27046481
TI  - Colorectal Tumors From Different Racial and Ethnic Minorities Have Similar Rates
      of Mismatch Repair Deficiency.
AB  - BACKGROUND & AIMS: Microsatellite instability (MSI) in colorectal cancer cells
      results from deficient mismatch repair (MMR) protein function, either acquired or
      from germline alterations such as in patients with Lynch syndrome. Universal
      screening initiatives for Lynch syndrome have been encouraged. However, little is
      known about the true prevalence of MMR deficiency and MSI in colorectal tumors
      among individuals from different racial and ethnic subgroups or their clinical
      effects in these populations. METHODS: We performed a retrospective analysis of
      253 surgically resected, primary colorectal adenocarcinoma specimens identified
      from the University of Miami tumor registry from 2005 through 2010. We collected
      clinical data, including overall survival (OS), the proportion of patients alive
      at specific intervals, from non-Hispanic white, Hispanic, and black patients
      matched by stage. We performed immunohistochemical staining to detect MMR
      proteins in all specimens and polymerase chain reaction analysis of 51 tumors to
      detect MSI. RESULTS: We detected MMR deficiency in 28 of 253 cases (11.1%),
      evenly distributed among blacks (9.6%), non-Hispanic whites (10.4%), and
      Hispanics (12.6%) (P = .79). Combined deficiencies in MLH1 and PMS2 were found in
      23 of 28 MMR-deficient samples (82.1%); MSH2 and MSH6 were most frequently absent
      in tumor samples from Hispanics (P = .03). Eleven of 51 tumor samples (21.6%) had
      high levels of MSI, and we observed a high level of concordance between MMR and
      MSI (kappa = .81). OS was significantly better in patients whose tumors had
      deficient MMR (hazard ratio for patients with MMR-deficient tumors vs MMR
      proteins intact = 0.37; 95% confidence interval, 0.15-0.91; P = .03). Race and
      ethnicity were not significant predictors of OS. CONCLUSIONS: MMR deficiency in
      colorectal tumors occurs with similar rates among patients of different racial
      and ethnic groups, which is based on immunohistochemical analysis of 253 primary
      tumor specimens. This finding indicates the potential value of universal testing
      of colorectal cancer by immunohistochemistry in minority populations and confirms
      the benefit of MMR deficiency to OS.

PMID- 27046482
TI  - Development and Validation of the Framingham Steatosis Index to Identify Persons
      With Hepatic Steatosis.
AB  - BACKGROUND & AIMS: Serum levels of aminotransferases are used as markers of
      nonalcoholic fatty liver disease in epidemiology research. However, it is not
      clear whether they can be used to identify patients with fatty liver. We
      investigated the accuracy of serum levels of aminotransferases in detection of
      hepatic steatosis. In addition, we derived a Framingham steatosis index (FSI) and
      tested its ability to identify patients with hepatic steatosis in an independent
      cohort. METHODS: We performed a cross-sectional study of 1181 members of the
      Framingham Third Generation Cohort (46.1% women; mean age, 50.3 +/- 6.7 years).
      People with hepatic steatosis were identified by computed tomography that was
      performed from 2008 through 2011. We compared the abilities of levels of alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) and the ratio of
      ALT:AST to identify people with hepatic steatosis by using c-statistic analyses.
      We performed a stepwise regression procedure to identify demographic and clinical
      factors that correlated with hepatic steatosis; we used these, along with
      biochemical factors associated with steatosis, to develop the FSI. We validated
      the FSI by using data from the third National Health and Nutrition Examination
      Survey. RESULTS: The prevalence of hepatic steatosis in the Framingham Third
      Generation Cohort was 26.8%. The ratio of ALT:AST identified people with hepatic
      steatosis with the highest c-statistic value (0.728); the value for only ALT was
      0.706, and the value for only AST was 0.589. We derived the FSI on the basis of
      patient age, sex, body mass index, levels of triglycerides, hypertension,
      diabetes, and ratio of ALT:AST. The FSI identified patients with hepatic
      steatosis with a c-statistic value of 0.845. When it was applied to the third
      National Health and Nutrition Examination Survey cohort, the FSI identified
      patients with steatosis with a c-statistic value of 0.760 and was well
      calibrated. CONCLUSIONS: In an analysis of the Framingham Third Generation
      Cohort, we found the ratio of ALT:AST to identify people with hepatic steatosis
      more accurately than either ALT or AST alone. We used data from this cohort to
      develop and validate the FSI, which identifies patients with steatosis with a c
      statistic value of about 0.8.

PMID- 27046483
TI  - Poor Performance Status Is Associated With Increased Mortality in Patients With
      Cirrhosis.
AB  - BACKGROUND & AIMS: Functional status (a patient's ability to perform activities
      that meet basic needs, fulfill usual roles, and maintain health and well-being)
      has been linked to outcomes in patients with cirrhosis and can be measured by the
      Karnofsky performance status (KPS) scale. We investigated the association between
      KPS score and mortality in patients with cirrhosis. METHODS: We used the United
      Network for Organ Sharing database to perform a retrospective cohort study of
      patients listed for liver transplantation in the United States between 2005 and
      2015. We used Cox proportional hazards and competing risk regression analyses to
      examine the association between KPS and mortality and transplantation. RESULTS:
      Of 79,092 patients, 44% were in KPS category A (KPS, 80%-100%), 43% were in
      category B (KPS, 50%-70%), and 13% were in category C (KPS, 10%-40%). Between
      2005 and 2015, the proportion of patients in category A decreased from 53% to
      35%, whereas the proportions in categories B and C increased from 36% to 49% and
      from 11% to 16%, respectively. KPS was associated with mortality: compared with
      patients in KPS category A, the KPS B adjusted hazard ratio (HR) was 1.14 (95%
      confidence interval [CI], 1.11-1.18) and the KPS C adjusted HR was 1.63 (95% CI,
      1.55-1.72). KPS was also associated with liver transplantation; compared with
      patients in KPS category A, the KPS B adjusted HR was 1.08 (95% CI, 1.06-1.11)
      and the KPS C adjusted HR was 1.35 (95% CI, 1.30-1.40). In competing risk
      analysis, only the relationship between KPS and mortality maintained significance
      and directionality. These relationships were most pronounced in patients without
      hepatocellular carcinoma. CONCLUSIONS: Among patients with cirrhosis listed for
      liver transplantation, poor performance status, based on the KPS scale, is
      associated with increased mortality. In this population, performance status has
      decreased over time.

PMID- 27046484
TI  - Quantification of Core Antigen Monitors Efficacy of Direct-acting Antiviral
      Agents in Patients With Chronic Hepatitis C Virus Infection.
AB  - BACKGROUND & AIMS: Widespread use of direct-acting antiviral (DAA) agents to
      treat patients with hepatitis C virus (HCV) infection has reduced the need for
      monitoring of HCV RNA levels, because viral kinetics do not predict sustained
      virologic response (SVR) to these drugs. However, the performance of cheaper
      tests such as the assay to quantify HCV core antigen (HCV Ag) has not been
      determined. We investigated the accuracy of the HCV Ag test in predicting which
      patients receiving DAAs will achieve SVRs at week 12 (SVR12). METHODS: We
      performed a prospective study of 58 patients infected with HCV genotypes 1-5 (45%
      with HCV genotype 1, 72% with cirrhosis) receiving DAA therapy from the Liver
      Center at the Universita degli Studi of Milan in Italy from January to March
      2015. We collected blood samples and measured levels of HCV Ag and HCV RNA at
      baseline, after 2 and 4 weeks of treatment, the end of treatment, and 12 weeks
      after treatment ended. We compared the ability of these assays to predict which
      patients would have SVR12. RESULTS: The median baseline level of HCV RNA was 5.79
      log10 IU/mL (range, 3.51-7.31 log10 IU/mL) and of HCV Ag was 3226.87 fmol/L
      (range, 17.30-54,927.00 fmol/L). HCV Ag became undetectable in 71% of patients at
      week 2, 84% at week 4, and 93% at the end of treatment. HCV RNA became
      undetectable in 10% of patients at week 2, 43% at week 4, and 100% at the end of
      treatment (P < .0001). Concordance between the tests in identifying patients who
      would achieve SVR12 was 40% at week 2, 55% at week 4, and 95% at the end of
      treatment. Fifty-three of 58 patients (91%) achieved an SVR12; the test for HCV
      Ag identified 97% of these patients. The tests for HCV Ag and HCV RNA predicted
      which patients would have SVR12 with positive predictive values of 90% vs 83%,
      respectively, at week 2 and 89% vs 92%, respectively, at week 4. CONCLUSIONS:
      Tests that measure HCV Ag monitor efficacy of DAA therapy for HCV infection as
      well as assays that measure HCV RNA and can be recommended for clinical practice.
      However, measurement of HCV RNA after treatment can rule out relapse in HCV Ag
      positive patients.

PMID- 27046486
TI  - "All of My Lovers Fit Into This Scale": Sexual Minority Individuals' Responses to
      Two Novel Measures of Sexual Orientation.
AB  - Previous qualitative research on traditional measures of sexual orientation raise
      concerns regarding how well these scales capture sexual minority individuals'
      experience of sexuality. The present research focused on the critique of two
      novel scales developed to better capture the way sexual and gender minority
      individuals conceptualize sexuality. Participants were 179 sexual minority (i.e.,
      gay, lesbian, bisexual, pansexual, queer, asexual) individuals who identified as
      cisgender (n = 122) and transgender (n = 57). Participants first completed the
      new scales, then provided qualitative responses regarding how well each scale
      captured their sexuality. The Sexual-Romantic Scale enabled the measurement of
      sexual and romantic attraction to each sex independently (same-sex and other
      sex). Participants resonated with the way the Sexual-Romantic scale disaggregated
      sexual and romantic attraction. Although cisgender monosexual (lesbian/gay)
      individuals positively responded to the separation of same- and other-sex
      attraction, individuals with either plurisexual (bisexual, pansexual, or fluid)
      or transgender identities found the binary conceptualization of sex/gender
      problematic. The Gender-Inclusive Scale incorporated same- and other-sex
      attraction as well as dimensions of attraction beyond those based on sex
      (attraction to masculine, feminine, androgynous, and gender non-conforming
      individuals). The incorporation of dimensions of sexual attraction outside of sex
      in the Gender-Inclusive Scale was positively regarded by participants of all
      identities. Findings indicate that the Sexual-Romantic and Gender-Inclusive
      scales appear to address some of the concerns raised in previous research
      regarding the measurement of sexual orientation among sexual minority
      individuals.

PMID- 27046485
TI  - Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present
      inactivated PRRSV antigen through TRIF/MyD88-NF-kappaB signaling pathway.
AB  - PRRS is one of the most important diseases in swine industry. Current PRRS
      inactivated vaccine provides only a limited protection and cannot induce
      sufficient cell-mediated immune responses. In this study, we first found that the
      mRNA and protein levels of Th1-type cytokines (IFN-gamma, IL-12) and Th2-type
      cytokines (IL-6, IL-10) were significantly increased through TRIF/MyD88-NF-kappaB
      signaling pathway when porcine peripheral blood monocyte-derived dendritic cells
      (MoDCs) were treated with poly (I: C) of TLR3 ligand and imiquimod of TLR7
      ligand, along with inactivated PRRSV antigen. Meanwhile, the ability of catching
      PRRSV antigen was also significantly enhanced. In mice experiment, it was found
      that the PRRSV-specific T lymphocyte proliferation, the percentages of CD4(+),
      CD8(+) T lymphocytes and PRRSV-specific CD3(+) T cells producing IFN-gamma and IL
      4, the levels of Th1- and Th2-type cytokines and the titers of neutralization
      antibody were significantly enhanced in poly (I: C), imiquimod along with
      inactivated PRRSV group. Taken together, results of our experiments described for
      the first time that synergy of TLR3 and 7 ligands could significantly enhance the
      function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-kappaB
      signaling pathway and be used as adjuvant candidate for the development of novel
      PRRS inactivated vaccine. 

PMID- 27046487
TI  - Decreased Linezolid Serum Concentrations in Three Critically Ill Patients:
      Clinical Case Studies of a Potential Drug Interaction between Linezolid and
      Rifampicin.
AB  - Linezolid is a valuable treatment option for treating infections caused by multi
      resistant gram-positive pathogens. Lack of effective linezolid levels due to the
      co-administration of rifampicin has been described in healthy subjects. However,
      the clinical significance of this potential drug interaction (DI) for critically
      ill patients is still unclear. This was a retrospective analysis of 3 critically
      ill patients with the combination therapy of linezolid and rifampicin or
      rifampicin pre-treatment. Despite increasing the dose of linezolid, the majority
      of observed linezolid trough concentrations in all 3 patients were below 2 mg/l.
      Furthermore, linezolid trough concentrations remained below 2 mg/l after
      discontinuation of rifampicin. This potential DI between linezolid and rifampicin
      could lead to treatment failure. Therefore, we strongly recommend that linezolid
      serum concentrations be monitored in patients with rifampicin co-administration
      or rifampicin pretreatment. 

PMID- 27046488
TI  - A Deterministic Analysis for LRR.
AB  - The recently proposed low-rank representation (LRR) method has been empirically
      shown to be useful in various tasks such as motion segmentation, image
      segmentation, saliency detection and face recognition. While potentially
      powerful, LRR depends heavily on the configuration of its key parameter, lambda.
      In realistic environments where the prior knowledge about data is lacking,
      however, it is still unknown how to choose lambda in a suitable way. Even more,
      there is a lack of rigorous analysis about the success conditions of the method,
      and thus the significance of LRR is a little bit vague. In this paper we
      therefore establish a theoretical analysis for LRR, striving for figuring out
      under which conditions LRR can be successful, and deriving a moderately good
      estimate to the key parameter lambda as well. Simulations on synthetic data
      points and experiments on real motion sequences verify our claims.

PMID- 27046489
TI  - Automatic Shadow Detection and Removal from a Single Image.
AB  - We present a framework to automatically detect and remove shadows in real world
      scenes from a single image. Previous works on shadow detection put a lot of
      effort in designing shadow variant and invariant hand-crafted features. In
      contrast, our framework automatically learns the most relevant features in a
      supervised manner using multiple convolutional deep neural networks (ConvNets).
      The features are learned at the super-pixel level and along the dominant
      boundaries in the image. The predicted posteriors based on the learned features
      are fed to a conditional random field model to generate smooth shadow masks.
      Using the detected shadow masks, we propose a Bayesian formulation to accurately
      extract shadow matte and subsequently remove shadows. The Bayesian formulation is
      based on a novel model which accurately models the shadow generation process in
      the umbra and penumbra regions. The model parameters are efficiently estimated
      using an iterative optimization procedure. Our proposed framework consistently
      performed better than the state-of-the-art on all major shadow databases
      collected under a variety of conditions. 

PMID- 27046490
TI  - Classification with Noisy Labels by Importance Reweighting.
AB  - In this paper, we study a classification problem in which sample labels are
      randomly corrupted. In this scenario, there is an unobservable sample with noise
      free labels. However, before being observed, the true labels are independently
      flipped with a probability rho ? [0,0.5), and the random label noise can be class
      conditional. Here, we address two fundamental problems raised by this scenario.
      The first is how to best use the abundant surrogate loss functions designed for
      the traditional classification problem when there is label noise. We prove that
      any surrogate loss function can be used for classification with noisy labels by
      using importance reweighting, with consistency assurance that the label noise
      does not ultimately hinder the search for the optimal classifier of the noise
      free sample. The other is the open problem of how to obtain the noise rate rho.
      We show that the rate is upper bounded by the conditional probability P(?Y|X) of
      the noisy sample. Consequently, the rate can be estimated, because the upper
      bound can be easily reached in classification problems. Experimental results on
      synthetic and real datasets confirm the efficiency of our methods.

PMID- 27046491
TI  - Contrastive Pessimistic Likelihood Estimation for Semi-Supervised Classification.
AB  - Improvement guarantees for semi-supervised classifiers can currently only be
      given under restrictive conditions on the data. We propose a general way to
      perform semi-supervised parameter estimation for likelihood-based classifiers for
      which, on the full training set, the estimates are never worse than the
      supervised solution in terms of the log-likelihood. We argue, moreover, that we
      may expect these solutions to really improve upon the supervised classifier in
      particular cases. In a worked-out example for LDA, we take it one step further
      and essentially prove that its semi-supervised version is strictly better than
      its supervised counterpart. The two new concepts that form the core of our
      estimation principle are contrast and pessimism. The former refers to the fact
      that our objective function takes the supervised estimates into account, enabling
      the semi-supervised solution to explicitly control the potential improvements
      over this estimate. The latter refers to the fact that our estimates are
      conservative and therefore resilient to whatever form the true labeling of the
      unlabeled data takes on. Experiments demonstrate the improvements in terms of
      both the log-likelihood and the classification error rate on independent test
      sets. 

PMID- 27046492
TI  - Heterogeneous Tensor Decomposition for Clustering via Manifold Optimization.
AB  - Tensor clustering is an important tool that exploits intrinsically rich
      structures in real-world multiarray or Tensor datasets. Often in dealing with
      those datasets, standard practice is to use subspace clustering that is based on
      vectorizing multiarray data. However, vectorization of tensorial data does not
      exploit complete structure information. In this paper, we propose a subspace
      clustering algorithm without adopting any vectorization process. Our approach is
      based on a novel heterogeneous Tucker decomposition model taking into account
      cluster membership information. We propose a new clustering algorithm that
      alternates between different modes of the proposed heterogeneous tensor model.
      All but the last mode have closed-form updates. Updating the last mode reduces to
      optimizing over the multinomial manifold for which we investigate second order
      Riemannian geometry and propose a trust-region algorithm. Numerical experiments
      show that our proposed algorithm compete effectively with state-of-the-art
      clustering algorithms that are based on tensor factorization. 

PMID- 27046493
TI  - Incremental Learning of Random Forests for Large-Scale Image Classification.
AB  - Large image datasets such as ImageNet or open-ended photo websites like Flickr
      are revealing new challenges to image classification that were not apparent in
      smaller, fixed sets. In particular, the efficient handling of dynamically growing
      datasets, where not only the amount of training data but also the number of
      classes increases over time, is a relatively unexplored problem. In this
      challenging setting, we study how two variants of Random Forests (RF) perform
      under four strategies to incorporate new classes while avoiding to retrain the
      RFs from scratch. The various strategies account for different trade-offs between
      classification accuracy and computational efficiency. In our extensive
      experiments, we show that both RF variants, one based on Nearest Class Mean
      classifiers and the other on SVMs, outperform conventional RFs and are well
      suited for incrementally learning new classes. In particular, we show that RFs
      initially trained with just 10 classes can be extended to 1,000 classes with an
      acceptable loss of accuracy compared to training from the full data and with
      great computational savings compared to retraining for each new batch of classes.

PMID- 27046494
TI  - Laplacian Regularized Low-Rank Representation and Its Applications.
AB  - Low-rank representation (LRR) has recently attracted a great deal of attention
      due to its pleasing efficacy in exploring low-dimensional subspace structures
      embedded in data. For a given set of observed data corrupted with sparse errors,
      LRR aims at learning a lowest-rank representation of all data jointly. LRR has
      broad applications in pattern recognition, computer vision and signal processing.
      In the real world, data often reside on low-dimensional manifolds embedded in a
      high-dimensional ambient space. However, the LRR method does not take into
      account the non-linear geometric structures within data, thus the locality and
      similarity information among data may be missing in the learning process. To
      improve LRR in this regard, we propose a general Laplacian regularized low-rank
      representation framework for data representation where a hypergraph Laplacian
      regularizer can be readily introduced into, i.e., a Non-negative Sparse Hyper
      Laplacian regularized LRR model (NSHLRR). By taking advantage of the graph
      regularizer, our proposed method not only can represent the global low
      dimensional structures, but also capture the intrinsic non-linear geometric
      information in data. The extensive experimental results on image clustering, semi
      supervised image classification and dimensionality reduction tasks demonstrate
      the effectiveness of the proposed method. 

PMID- 27046495
TI  - Multi-Directional Multi-Level Dual-Cross Patterns for Robust Face Recognition.
AB  - To perform unconstrained face recognition robust to variations in illumination,
      pose and expression, this paper presents a new scheme to extract "Multi
      Directional Multi-Level Dual-Cross Patterns" (MDML-DCPs) from face images.
      Specifically, the MDML-DCPs scheme exploits the first derivative of Gaussian
      operator to reduce the impact of differences in illumination and then computes
      the DCP feature at both the holistic and component levels. DCP is a novel face
      image descriptor inspired by the unique textural structure of human faces. It is
      computationally efficient and only doubles the cost of computing local binary
      patterns, yet is extremely robust to pose and expression variations. MDML-DCPs
      comprehensively yet efficiently encodes the invariant characteristics of a face
      image from multiple levels into patterns that are highly discriminative of inter
      personal differences but robust to intra-personal variations. Experimental
      results on the FERET, CAS-PERL-R1, FRGC 2.0, and LFW databases indicate that DCP
      outperforms the state-of-the-art local descriptors (e.g., LBP, LTP, LPQ, POEM,
      tLBP, and LGXP) for both face identification and face verification tasks. More
      impressively, the best performance is achieved on the challenging LFW and FRGC
      2.0 databases by deploying MDML-DCPs in a simple recognition scheme. 

PMID- 27046496
TI  - Object Discovery: Soft Attributed Graph Mining.
AB  - We categorize this research in terms of its contribution to both graph theory and
      computer vision. From the theoretical perspective, this study can be considered
      as the first attempt to formulate the idea of mining maximal frequent subgraphs
      in the challenging domain of messy visual data, and as a conceptual extension to
      the unsupervised learning of graph matching. We define a soft attributed pattern
      (SAP) to represent the common subgraph pattern among a set of attributed
      relational graphs (ARGs), considering both their structure and attributes.
      Regarding the differences between ARGs with fuzzy attributes and conventional
      labeled graphs, we propose a new mining strategy that directly extracts the SAP
      with the maximal graph size without applying node enumeration. Given an initial
      graph template and a number of ARGs, we develop an unsupervised method to modify
      the graph template into the maximal-size SAP. From a practical perspective, this
      research develops a general platform for learning the category model (i.e., the
      SAP) from cluttered visual data (i.e., the ARGs) without labeling "what is
      where," thereby opening the possibility for a series of applications in the era
      of big visual data. Experiments demonstrate the superior performance of the
      proposed method on RGB/RGB-D images and videos. 

PMID- 27046497
TI  - One Shot Detection with Laplacian Object and Fast Matrix Cosine Similarity.
AB  - One shot, generic object detection involves searching for a single query object
      in a larger target image. Relevant approaches have benefited from features that
      typically model the local similarity patterns. In this paper, we combine local
      similarity (encoded by local descriptors) with a global context (i.e., a graph
      structure) of pairwise affinities among the local descriptors, embedding the
      query descriptors into a low dimensional but discriminatory subspace. Unlike
      principal components that preserve global structure of feature space, we actually
      seek a linear approximation to the Laplacian eigenmap that permits us a locality
      preserving embedding of high dimensional region descriptors. Our second
      contribution is an accelerated but exact computation of matrix cosine similarity
      as the decision rule for detection, obviating the computationally expensive
      sliding window search. We leverage the power of Fourier transform combined with
      integral image to achieve superior runtime efficiency that allows us to test
      multiple hypotheses (for pose estimation) within a reasonably short time. Our
      approach to one shot detection is training-free, and experiments on the standard
      data sets confirm the efficacy of our model. Besides, low computation cost of the
      proposed (codebook-free) object detector facilitates rather straightforward query
      detection in large data sets including movie videos. 

PMID- 27046498
TI  - Robust Subjective Visual Property Prediction from Crowdsourced Pairwise Labels.
AB  - The problem of estimating subjective visual properties from image and video has
      attracted increasing interest. A subjective visual property is useful either on
      its own (e.g. image and video interestingness) or as an intermediate
      representation for visual recognition (e.g. a relative attribute). Due to its
      ambiguous nature, annotating the value of a subjective visual property for
      learning a prediction model is challenging. To make the annotation more reliable,
      recent studies employ crowdsourcing tools to collect pairwise comparison labels.
      However, using crowdsourced data also introduces outliers. Existing methods rely
      on majority voting to prune the annotation outliers/errors. They thus require a
      large amount of pairwise labels to be collected. More importantly as a local
      outlier detection method, majority voting is ineffective in identifying outliers
      that can cause global ranking inconsistencies. In this paper, we propose a more
      principled way to identify annotation outliers by formulating the subjective
      visual property prediction task as a unified robust learning to rank problem,
      tackling both the outlier detection and learning to rank jointly. This differs
      from existing methods in that (1) the proposed method integrates local pairwise
      comparison labels together to minimise a cost that corresponds to global
      inconsistency of ranking order, and (2) the outlier detection and learning to
      rank problems are solved jointly. This not only leads to better detection of
      annotation outliers but also enables learning with extremely sparse annotations.

PMID- 27046499
TI  - Towards Open-World Person Re-Identification by One-Shot Group-Based Verification.
AB  - Solving the problem of matching people across non-overlapping multi-camera views,
      known as person re-identification (re-id), has received increasing interests in
      computer vision. In a real-world application scenario, a watch-list (gallery set)
      of a handful of known target people are provided with very few (in many cases
      only a single) image(s) (shots) per target. Existing re-id methods are largely
      unsuitable to address this open-world re-id challenge because they are designed
      for (1) a closed-world scenario where the gallery and probe sets are assumed to
      contain exactly the same people, (2) person-wise identification whereby the model
      attempts to verify exhaustively against each individual in the gallery set, and
      (3) learning a matching model using multi-shots. In this paper, a novel transfer
      local relative distance comparison (t-LRDC) model is formulated to address the
      open-world person re-identification problem by one-shot group-based verification.
      The model is designed to mine and transfer useful information from a labelled
      open-world non-target dataset. Extensive experiments demonstrate that the
      proposed approach outperforms both non-transfer learning and existing transfer
      learning based re-id methods. 

PMID- 27046500
TI  - Unsupervised Many-to-Many Object Matching for Relational Data.
AB  - We propose a method for unsupervised many-to-many object matching from multiple
      networks, which is the task of finding correspondences between groups of nodes in
      different networks. For example, the proposed method can discover shared word
      groups from multi-lingual document-word networks without cross-language alignment
      information. We assume that multiple networks share groups, and each group has
      its own interaction pattern with other groups. Using infinite relational models
      with this assumption, objects in different networks are clustered into common
      groups depending on their interaction patterns, discovering a matching. The
      effectiveness of the proposed method is experimentally demonstrated by using
      synthetic and real relational data sets, which include applications to cross
      domain recommendation without shared user/item identifiers and multi-lingual word
      clustering. 

PMID- 27046501
TI  - Preimplantation genetic screening - what a wonderful world it would be!

PMID- 27046502
TI  - The P-value and the problem of multiple testing.

PMID- 27046503
TI  - Corrigendum to "What's in a name? Variations in terminology of third-party
      reproduction" [Reproductive BioMedicine Online 31 (2015) 805-814].
AB  - The authors regret that the reference "Dickenson, 2012" was incomplete in the
      reference list. Full reference details are given below: Dickenson, D., 2012.
      Bioethics: All That Matters. Hodder Education, London. The authors would like to
      apologise for any inconvenience caused.

PMID- 27046505
TI  - Origin of the Red-Shifted Optical Spectra Recorded for Aza-BODIPY Dyes.
AB  - The optical properties are compared for two boron dipyrromethene (BODIPY) dyes
      that differ by virtue of the substituent at the meso-site, namely, aza-N versus C
      methine atoms. Both compounds are equipped with aryl rings at the 3- and 5
      positions of the dipyrrin backbone, which help to extend the degree of pi
      delocalization. The aza-BODIPY dye absorbs and fluoresces at much lower energy
      than does the conventional BODIPY dye, with red shifts of about 100 nm being
      observed in fluid solution, but with comparable fluorescence yield and lifetime.
      Hydrogen bonding donors, such as alcohols, attach to the aza-N atom and promote
      nonradiative decay without affecting the properties of the conventional dye.
      Triplet formation is ineffective in the absence of a spin-orbit coupler. Quantum
      chemical calculations indicate that the electronegative aza-N atom lowers the
      energy of the LUMO while having little effect on the corresponding HOMO energy.
      The resultant decrease in the HOMO-LUMO energy gap is primarily responsible for
      the red shift. The HOMO-LUMO energy gap is also affected by the dihedral angle
      subtended by the aryl rings, but this is insensitive to the geometry around the
      central 6-membered ring. The aza-N atom, by virtue of restricting spatial overlap
      between the HOMO and LUMO, decreases the energy gap between excited-singlet and 
      triplet states.

PMID- 27046504
TI  - Comparison of nicotine dependence indicators in predicting quitting among
      pregnant smokers.
AB  - Research in the general population of smokers indicates that across various
      measures of nicotine dependence, time to first cigarette (TTFC) is the strongest
      single-item predictor of quitting success. Whether those findings generalize to
      pregnant smokers is unclear. To investigate this matter, we compared TTFC with
      cigarettes per day (CPD) and the Heaviness of Smoking Index (HSI; Kozlowski,
      Porter, Orleans, Pope, & Heatherton, 1994) in predicting late-pregnancy
      abstinence among 289 pregnant women enrolled in 4 smoking-cessation trials
      assessing the efficacy of financial incentives. Logistic regression was used to
      compare predictors, with model fit measured using the c statistic (range = 0.5,
      poor prediction to 1.0, perfect prediction). In simple regressions, model fit was
      comparable across the 3 measures although strongest for CPD alone (c = 0.70,
      0.68, 0.66 for CPD, HSI, and TTFC, respectively). In a stepwise multiple
      regression, treatment was entered first (c = 0.67), then CPD (c = 0.77), quit
      attempts prepregnancy (c = .81), TTFC (c = .82), and quit attempts during
      pregnancy (c = .83). We saw no evidence supporting TTFC as the optimal predictor
      of quitting among pregnant smokers. Instead, the evidence supported using CPD and
      TTFC together or CPD alone if using only a single predictor. 

PMID- 27046506
TI  - Adsorption of Plasma Proteins onto PEGylated Lipid Bilayers: The Effect of PEG
      Size and Grafting Density.
AB  - Lipid bilayers grafted with polyethylene glycol (PEG) of different sizes (Mw =
      750, 2000, and 5000) and grafting densities (1.6-25 mol % of PEGylated lipid in
      dipalmitoylphosphatidylcholine (DPPC) lipid molecules) were simulated with human
      serum albumin (HSA) using coarse-grained force fields. At low enough grafting
      density, the PEG has a conformation similar to that of an isolated chain in
      water, and its Flory radius RF is smaller than the distance between the grafting
      points (d), which is the so-called "mushroom" regime. In contrast, densely
      grafted PEG chains (RF > d) extend like brushes, with brush layer thickness given
      by the Alexander-de Gennes theory. A nearly spherical HSA added to this
      simulation migrates to the bilayer surface because of the charge interactions
      between anion residues of HSA and cationic cholines of DPPC, but this HSA-bilayer
      binding can be sterically suppressed by the PEG chains to an extent that depends
      on the PEG size and grafting density. In particular, regardless of the extent of
      the coverage of the PEG on the bilayer, the binding between HSAs and bilayers is
      suppressed by the PEG layer in a brush but not in a mushroom, indicating that the
      attractive force between proteins and bilayers can overcome the steric effect of
      the PEG layer in the mushroom state or in the transition region from mushroom to
      brush. This helps explain and clarify experiments that show much less adsorption
      of plasma proteins onto the particle or membrane surface when PEGs are in the
      brush rather than in the mushroom state.

PMID- 27046507
TI  - Efficient photocatalytic degradation of ibuprofen in aqueous solution using novel
      visible-light responsive graphene quantum dot/AgVO3 nanoribbons.
AB  - Single crystalline, non-toxicity, and long-term stability graphene quantum dots
      (GQDs) were modified onto the AgVO3 nanoribbons by a facile hydrothermal and
      sintering technique which constructs a unique heterojunction photocatalyst.
      Characterization results indicate that GQDs are well dispersed on the surface of
      AgVO3 nanoribbons and GQD/AgVO3 heterojunctions are formed, which can greatly
      promote the separation efficiency of photogenerated electron-hole pairs under
      visible light irradiation. By taking advantage of this feature, the GQD/AgVO3
      heterojunctions exhibit considerable improvement on the photocatalytic activities
      for the degradation of ibuprofen (IBP) under visible light irradiation as
      compared to pure AgVO3. The photocatalytic activity of GQD/AgVO3 heterojunctions
      is relevant with GQD ratio and the optimal activity is obtained at 3wt% with the
      highest separation efficiency of photogenerated electron-hole pairs. Integrating
      the physicochemical and photocatalytic properties, the factors controlling the
      photocatalytic activity of GQD/AgVO3 heterojunctions are discussed in detail.
      Moreover, potential photocatalytic degradation mechanisms of IBP via GQD/AgVO3
      heterojunctions under visible light are proposed.

PMID- 27046508
TI  - Negative covariance between parasite load and body condition in a population of
      feral horses.
AB  - In wild and domestic animals, gastrointestinal parasites can have significant
      impacts on host development, condition, health, reproduction and longevity.
      Improving our understanding of the causes and consequences of individual-level
      variation in parasite load is therefore of prime interest. Here we investigated
      the relationship between strongyle fecal egg count (FEC) and body condition in a
      unique, naturalized population of horses that has never been exposed to
      anthelmintic drugs (Sable Island, Nova Scotia, Canada). We first quantified
      variation in FEC and condition for 447 individuals according to intrinsic (sex,
      age, reproductive status, social status) and extrinsic (group size, location,
      local density) variables. We then quantified the repeatability of measurements
      obtained over a field season and tested for covariance between FEC and condition.
      FECs were high relative to other horse populations (mean eggs per gram +/- SD =
      1543.28 +/- 209.94). FECs generally decreased with age, were higher in lactating
      vs non-lactating females, and unexpectedly lower in males in some part of the
      island. FECs and condition were both spatially structured, with patterns
      depending on age, sex and reproductive status. FECs and condition were both
      repeatable. Most notably, FECs and condition were negatively correlated,
      especially in adult females.

PMID- 27046509
TI  - Development of an Online Cell-Based Bioactivity Screening Method by Coupling
      Liquid Chromatography to Flow Cytometry with Parallel Mass Spectrometry.
AB  - This study describes a new platform for the fast and efficient functional
      screening for bioactive compounds in complex natural mixtures using a cell-based
      assay. The platform combines reversed-phase liquid chromatography (LC) with
      online flow cytometry (FC) and mass spectrometry (MS). As a model (an example or
      proof-of-concept study) we have used a functional calcium-flux assay in human
      neuroblastoma SH-SY5Y cells stably overexpressing the alpha-7 nicotinic
      acetylcholine receptor (alpha7-nAChR), a potential therapeutic target for central
      nervous system (CNS) related diseases. We have designed the coupled LC-FC system
      employing the neuroblastoma cells followed by analytical and pharmacological
      evaluation of the hyphenated setup in agonist and mixed antagonist-agonist assay
      modes. Using standard receptor ligands we have validated pharmacological
      responses and standardized good assay quality parameters. The applicability of
      the screening system was evaluated by analysis of various types of natural
      samples, such as a tobacco plant extract (in agonist assay mode) and snake venoms
      (in mixed antagonist-agonist assay mode). The bioactivity responses were
      correlated directly to the respective accurate masses of the compounds. Using
      simultaneous functional agonist and antagonist responses nicotine and known
      neurotoxins were detected from tobacco extract and snake venoms, respectively.
      Thus, the developed analytical screening technique represents a new tool for
      rapid measurement of functional cell-based responses and parallel separation and
      identification of compounds in complex mixtures targeting the alpha7-nAChR. It is
      anticipated that other fast-response cell-based assays (e.g., other ion flux
      assays) can be incorporated in this analytical setup.

PMID- 27046510
TI  - Mechanical Behavior of a Bacillus subtilis Pellicle.
AB  - Bacterial biofilms consist of a complex network of biopolymers embedded with
      microorganisms, and together these components form a physically robust structure
      that enables bacteria to grow in a protected environment. This structure can help
      unwanted biofilms persist in situations ranging from chronic infection to the
      biofouling of industrial equipment, but under certain circumstances it can allow
      the biofilm to disperse and colonize new niches. Mechanical properties are
      therefore a key aspect of biofilm life. In light of the recently discovered
      growth-induced compressive stress present within a biofilm, we studied the
      mechanical behavior of Bacillus subtilis pellicles, or biofilms at the air-liquid
      interface, and tracked simultaneously the force response and macroscopic
      structural changes during elongational deformations. We observed that pellicles
      behaved viscoelastically in response to small deformations, such that the growth
      induced compressive stress was still present, and viscoplastically at large
      deformations, when the pellicles were under tension. In addition, by using
      particle imaging velocimetry we found that the pellicle deformations were
      nonaffine, indicating heterogeneous mechanical properties with the pellicle being
      more pliable near attachment surfaces. Overall, our results indicate that we must
      consider not only the viscoelastic but also the viscoplastic and mechanically
      heterogeneous nature of these structures to understand biofilm dispersal and
      removal.

PMID- 27046511
TI  - Senior Undergraduate Nursing Students' Perceptions of Disaster Preparedness: A
      Descriptive Study.
AB  - OBJECTIVE: This descriptive study aimed to determine the disaster preparedness of
      a senior class of undergraduate nursing students. METHODS: The study sample was
      composed of 73 undergraduate nursing school students from Ankara, Turkey. Data
      were collected by using a questionnaire developed by the researchers and were
      evaluated with descriptive statistics. RESULTS: More than half (56.1%) of the
      students stated that the disaster competencies of nurses should include
      leadership, manager, and coordinator skills; 42.4% of them indicated the
      competencies of decision-maker, critical thinking, autonomy, and planning skills.
      Regarding education, 56.4% of the students considered their education on disaster
      nursing as "efficient"; however, 35.9% of them considered their education as
      "partly efficient" or "inefficient." CONCLUSIONS: Many correct concepts related
      to the definition, features, competencies, and roles of disaster nurses were
      stated by students. However, low percentages and insufficient statements showed
      low preparedness for disasters. Curriculum development or redesign is necessary
      to include content and clinical experiences related to disasters. (Disaster Med
      Public Health Preparedness. 2016;0:1-5).

PMID- 27046512
TI  - The challenges of the first migration: movement and behaviour of juvenile vs.
      adult white storks with insights regarding juvenile mortality.
AB  - Migration conveys an immense challenge, especially for juvenile birds coping with
      enduring and risky journeys shortly after fledging. Accordingly, juveniles
      exhibit considerably lower survival rates compared to adults, particularly during
      migration. Juvenile white storks (Ciconia ciconia), which are known to rely on
      adults during their first fall migration presumably for navigational purposes,
      also display much lower annual survival than adults. Using detailed GPS and body
      acceleration data, we examined the patterns and potential causes of age-related
      differences in fall migration properties of white storks by comparing first-year
      juveniles and adults. We compared juvenile and adult parameters of movement,
      behaviour and energy expenditure (estimated from overall dynamic body
      acceleration) and placed this in the context of the juveniles' lower survival
      rate. Juveniles used flapping flight vs. soaring flight 23% more than adults and
      were estimated to expend 14% more energy during flight. Juveniles did not
      compensate for their higher flight costs by increased refuelling or resting
      during migration. When juveniles and adults migrated together in the same flock,
      the juvenile flew mostly behind the adult and was left behind when they
      separated. Juveniles showed greater improvement in flight efficiency throughout
      migration compared to adults which appears crucial because juveniles exhibiting
      higher flight costs suffered increased mortality. Our findings demonstrate the
      conflict between the juveniles' inferior flight skills and their urge to keep up
      with mixed adult-juvenile flocks. We suggest that increased flight costs are an
      important proximate cause of juvenile mortality in white storks and likely in
      other soaring migrants and that natural selection is operating on juvenile
      variation in flight efficiency.

PMID- 27046513
TI  - Generation of large coherent states by bang-bang control of a trapped-ion
      oscillator.
AB  - Fast control of quantum systems is essential to make use of quantum properties
      before they degrade by decoherence. This is important for quantum-enhanced
      information processing, as well as for pushing quantum systems towards the
      boundary between quantum and classical physics. 'Bang-bang' control attains the
      ultimate speed limit by making large changes to control fields much faster than
      the system can respond, but is often challenging to implement experimentally.
      Here we demonstrate bang-bang control of a trapped-ion oscillator using
      nanosecond switching of the trapping potentials. We perform controlled
      displacements with which we realize coherent states with up to 10,000 quanta of
      energy. We use these displaced states to verify the form of the ion-light
      interaction at high excitations far outside the usual regime of operation. These
      methods provide new possibilities for quantum-state manipulation and generation,
      alongside the potential for a significant increase in operational clock speed for
      trapped-ion quantum information processing. 

PMID- 27046514
TI  - Feasibility of assessing pulmonary blood volume using C-arm CT during
      transpulmonary chemoperfusion and chemoembolization in primary and secondary lung
      tumours.
AB  - OBJECTIVE: Assessment of parenchymal blood volume (PBV) of primary and secondary
      pulmonary malignancies by using a C-arm CT, regarding its role in detecting early
      functional response to transpulmonary chemoembolization (TPCE) and clinical
      practicability. METHODS: 21 patients with a mean age of 56.77 years, who were
      assigned to TPCE during their palliative treatment, were included. PBV and the
      diameter of tumours were analyzed. PBV maps were calculated from three
      dimensional CT-angiographic (3D-CTA) data sets. Imaging was performed on a flat
      detector, C-arm CT. Groups of response were classified according to the criteria
      of the response evaluation criteria in solid tumours. Statistically significant
      differences were determined and Pearson's regression analysis correlated PBV and
      diameter as parameters of response to treatment. RESULTS: During 4.91 sessions,
      median diameter increased 18.18% (p > 0.05) and PBV reduced 39.62% (p > 0.05).
      Functional and imaging response per tumour was statistical significantly
      different (p <= 0.05). Correlation coefficient was r = 0.058. 2/41 tumours showed
      partial response; 31/41 tumours showed stable disease; and 8/41 tumours showed
      progressive disease. The highest pre-treatment PBV values were measured in
      decreasing tumours (206.93 ml l(-1)), and the lowest values were measured in
      increasing tumours (60.17 ml l(-1); p > 0.05). The lowest values were also
      measured in lung cancer (53.02 ml l(-1)) that was significantly different to
      uterine leiomyosarcoma (103.31 ml l(-1)) and renal cell cancer (113.14 ml l(-1);
      p <= 0.05). CONCLUSION: Assessment of PBV maps by using 3D-CTA image data is
      feasible in the clinical routine. PBV shows a stronger response to TPCE treatment
      than measurement in diameter and should be considered as a response parameter for
      early detection. ADVANCES IN KNOWLEDGE: Assessment of PBV using C-arm CT during
      TPCE is a feasible technique. Assessment of PBV might be useful in assessing
      response to treatment.

PMID- 27046515
TI  - Homocysteinemia due to MTHFR deficiency in a young adult presenting with
      bilateral lens subluxations.
AB  - The most common cause of isolated inherited homocysteinemia is a deficiency of
      the enzyme cystathionine beta-synthase (CBS). Clinical manifestations of CBS
      deficiency can include ectopia lentis, thromboembolism, marfanoid habits, and
      intellectual disability. CBS deficiency, which affects the transsulfuration
      pathway, is marked biochemically by elevated serum homocysteine and plasma
      methionine. We report a patient with homocysteinemia, low plasma methionine, and
      no significant neurological abnormalities who presented with bilateral subluxated
      crystalline lenses due to a 5,10-methylenetetrahydrofolate reductase (MTHFR)
      deficiency. MTHFR deficiency, a disorder in the remethylation pathway, can cause
      mild to severe disease, although most presentations include neurological
      involvement. MTHFR deficiency has not been previously associated with lens
      subluxation or complete dislocation. Prolonged exposure to elevated serum
      homocysteine levels is most likely the explanation for her ectopia lentis. This
      case expands the differential diagnosis of homocysteinemia and highlights the
      need for a correct diagnosis to optimize the clinical outcome of patients with
      this condition.

PMID- 27046516
TI  - Construction and characterization of a highly reactive chicken-derived single
      chain variable fragment (scFv) antibody against Staphylococcus aureus developed
      with the T7 phage display system.
AB  - The purpose of this study was to construct a single-chain variable fragment
      (scFv) antibody from chicken egg yolk immunoglobulin (IgY) by means of genetic
      engineering and subsequent panning for a specific antibody against Staphylococcus
      aureus. METHODS AND RESULTS: We amplified the scFv using blood and spleen
      obtained from 100-day-old Roman chickens immunized with inactivated S. aureus and
      subsequently constructed a T7 phage display antibody library using phage display
      technology. Four non-repeated blood scFv and 6 spleen scFv were obtained
      following 3 rounds of panning of the T7 phage display antibody library, enzyme
      linked immunosorbent assay and sequencing. These 10 scFv were cloned into the
      prokaryotic expression vector pCold I with expression induced at a low
      temperature. Four soluble proteins were obtained. Among them, soluble protein
      SFV6 derived from the spleen showed good reactivity against S. aureus using
      indirect ELISA and produced a particularly strong antibacterial effect in vitro.
      CONCLUSION: We were successful in isolating a highly specific scFv antibody
      against S. aureus from the spleen phage display library. This study provides a
      simple and rapid method for the quick preparation of a large number of antibodies
      against S. aureus and provides the foundation for the positioning of antibodies
      in the organism and the study of the antibacterial mechanism through which the
      antibody functions.

PMID- 27046517
TI  - Interexaminer variation of minutia markup on latent fingerprints.
AB  - Latent print examiners often differ in the number of minutiae they mark during
      analysis of a latent, and also during comparison of a latent with an exemplar.
      Differences in minutia counts understate interexaminer variability: examiners'
      markups may have similar minutia counts but differ greatly in which specific
      minutiae were marked. We assessed variability in minutia markup among 170
      volunteer latent print examiners. Each provided detailed markup documenting their
      examinations of 22 latent-exemplar pairs of prints randomly assigned from a pool
      of 320 pairs. An average of 12 examiners marked each latent. The primary factors
      associated with minutia reproducibility were clarity, which regions of the prints
      examiners chose to mark, and agreement on value or comparison determinations. In
      clear areas (where the examiner was "certain of the location, presence, and
      absence of all minutiae"), median reproducibility was 82%; in unclear areas,
      median reproducibility was 46%. Differing interpretations regarding which regions
      should be marked (e.g., when there is ambiguity in the continuity of a print)
      contributed to variability in minutia markup: especially in unclear areas, marked
      minutiae were often far from the nearest minutia marked by a majority of
      examiners. Low reproducibility was also associated with differences in value or
      comparison determinations. Lack of standardization in minutia markup and
      unfamiliarity with test procedures presumably contribute to the variability we
      observed. We have identified factors accounting for interexaminer variability;
      implementing standards for detailed markup as part of documentation and focusing
      future training efforts on these factors may help to facilitate transparency and
      reduce subjectivity in the examination process.

PMID- 27046518
TI  - Role of glutamate receptors and glial cells in the pathophysiology of treatment
      resistant depression.
AB  - Treatment-resistant depression (TRD) causes substantial socioeconomic burden.
      Although a consensus on the definition of TRD has not yet been reached, it is
      certain that classic monoaminergic antidepressants are ineffective for TRD. One
      decade ago, many researchers found ketamine, an N-methyl-d-aspartate receptor
      (NMDAR) antagonist, to be an alternative to classic monoaminergic
      antidepressants. The major mechanisms of action of ketamine rapidly induce
      synaptogenesis in the brain-derived neurotrophic factor (BDNF) pathway. Although
      excessive glutamatergic neurotransmission and consequent excitotoxicity were
      considered a major cause of TRD, recent evidence suggests that the extrasynaptic
      glutamatergic receptor signal pathway mainly contributes to the detrimental
      effects of TRD. Glial cells such as microglia and astrocytes, early life
      adversity, and glucocorticoid receptor dysfunction participate in complex cross
      talk. An appropriate reuptake of glutamate at the astrocyte is crucial for
      preventing 'spill-over' of synaptic glutamate and binding to the extrasynaptic
      NMDA receptor. Excessive microglial activation and the inflammatory process cause
      astrocyte glutamatergic dysfunction, which in turn activates microglial function.
      Early life adversity and glucocorticoid receptor dysfunction result in
      vulnerability to stress in adulthood. A maladaptive response to stress leads to
      increased glutamatergic release and pro-inflammatory cytokines, which then
      activate microglia. However, since the role of inflammatory mediators such as pro
      inflammatory cytokines is not specific for depression, more disease-specific
      mechanisms should be identified. Last, although much research has focused on
      ketamine as an alternative antidepressant for TRD, its long-lasting effectiveness
      and adverse events have not been rigorously demonstrated. Additionally, evidence
      suggests that substantial brain abnormalities develop in ketamine abusers. Thus,
      more investigations for ketamine and other novel glutamatergic agents are needed.

PMID- 27046519
TI  - Maternal weight trajectories between early pregnancy and four and nine months
      postpartum.

PMID- 27046520
TI  - Practicability of detecting somatic point mutation from RNA high throughput
      sequencing data.
AB  - Traditionally, somatic mutations are detected by examining DNA sequence. The
      maturity of sequencing technology has allowed researchers to screen for somatic
      mutations in the whole genome. Increasingly, researchers have become interested
      in identifying somatic mutations through RNAseq data. With this motivation, we
      evaluated the practicability of detecting somatic mutations from RNAseq data.
      Current somatic mutation calling tools were designed for DNA sequencing data. To
      increase performance on RNAseq data, we developed a somatic mutation caller GLMVC
      based on bias reduced generalized linear model for both DNA and RNA sequencing
      data. Through comparison with MuTect and Varscan we showed that GLMVC performed
      better for somatic mutation detection using exome sequencing or RNAseq data.
      GLMVC is freely available for download at the following website:
      https://github.com/shengqh/GLMVC/wiki.

PMID- 27046521
TI  - The Secret of the Care of the Doctor Is in Caring for the Doctor.

PMID- 27046522
TI  - Longitudinal Study Evaluating the Association Between Physician Burnout and
      Changes in Professional Work Effort.
AB  - OBJECTIVE: To longitudinally evaluate the relationship between burnout and
      professional satisfaction with changes in physicians' professional effort.
      PARTICIPANTS AND METHODS: Administrative/payroll records were used to
      longitudinally evaluate the professional work effort of faculty physicians
      working for Mayo Clinic from October 1, 2008, to October 1, 2014. Professional
      effort was measured in full-time equivalent (FTE) units. Physicians were
      longitudinally surveyed in October 2011 and October 2013 with standardized tools
      to assess burnout and satisfaction. RESULTS: Between 2008 and 2014, the
      proportion of physicians working less than full-time at our organization
      increased from 13.5% to 16.0% (P=.05). Of the 2663 physicians surveyed in 2011
      and 2776 physicians surveyed in 2013, 1856 (69.7%) and 2132 (76.9%),
      respectively, returned surveys. Burnout and satisfaction scores in 2011
      correlated with actual reductions in FTE over the following 24 months as
      independently measured by administrative/payroll records. After controlling for
      age, sex, site, and specialty, each 1-point increase in the 7-point emotional
      exhaustion scale was associated with a greater likelihood of reducing FTE (odds
      ratio [OR], 1.43; 95% CI, 1.23-1.67; P<.001) over the following 24 months, and
      each 1-point decrease in the 5-point satisfaction score was associated with
      greater likelihood of reducing FTE (OR, 1.34; 95% CI, 1.03-1.74; P=.03). On
      longitudinal analysis at the individual physician level, each 1-point increase in
      emotional exhaustion (OR, 1.28; 95% CI, 1.05-1.55; P=.01) or 1-point decrease in
      satisfaction (OR, 1.67; 95% CI, 1.19-2.35; P=.003) between 2011 and 2013 was
      associated with a greater likelihood of reducing FTE over the following 12
      months. CONCLUSION: Among physicians in a large health care organization, burnout
      and declining satisfaction were strongly associated with actual reductions in
      professional work effort over the following 24 months.

PMID- 27046523
TI  - Lubiprostone Is Effective in the Treatment of Chronic Idiopathic Constipation and
      Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized
      Controlled Trials.
AB  - OBJECTIVE: To evaluate the efficacy and safety of lubiprostone in the treatment
      of chronic idiopathic constipation (CIC) and irritable bowel syndrome with
      constipation (IBS-C). PATIENTS AND METHODS: We performed a literature search of
      the MEDLINE, Cochrane, Google Scholar, and ClinicalTrials.gov databases (from
      January 1, 2005, through January 31, 2015). Relevant studies meeting the
      inclusion criteria were manually searched by 2 independent reviewers. Efficacy
      outcomes evaluated at 1 week, 1 month, and 3 months of intervention were weekly
      frequency of spontaneous bowel movements, severity of constipation, consistency
      of stools, degree of abdominal pain/discomfort, degree of straining, and
      abdominal bloating. RESULTS: Of 246 studies identified, data from 9 trials
      comprising 1468 patients (63.6%) in the lubiprostone group and 841 (36.4%) in the
      placebo group were analyzed. We found that lubiprostone treatment significantly
      improved the severity of constipation, stool consistency, abdominal pain, degree
      of straining, and abdominal bloating at 1 week (P<=.03) and 1 month (P<=.004),
      except for abdominal pain at 1 month, which was similar to that when treated with
      placebo (P=.21). At 3 months, except for abdominal bloating (P=.03), there was no
      difference between lubiprostone and placebo groups in all other outcomes
      (P>=.05). Adverse effects such as nausea, vomiting, and diarrhea were common
      (incidence rate, 2.4%-75%); however, the incidence of serious adverse effects was
      low (<5%) and was mostly unrelated to lubiprostone treatment. CONCLUSION:
      Lubiprostone is a safe and efficacious drug for the treatment of chronic
      idiopathic constipation and irritable bowel syndrome with constipation, with
      limited adverse effects in 3 months of follow-up.

PMID- 27046524
TI  - Zika Virus in the Americas: A Review for Clinicians.
AB  - Zika virus has recently emerged as a new public health threat. An arthropod-borne
      virus named after the Zika forest in Uganda, it was first discovered in 1947. The
      virus caused only sporadic cases of Zika infection in Africa and Southeast Asia
      until 2007, when the first large outbreak occurred in the Yap State in the
      Federated States of Micronesia. Another outbreak in French Polynesia in 2013 was
      notable for being associated temporally with an increase in cases of Guillain
      Barre syndrome. In 2015, the virus was first reported in Brazil and since then
      has spread explosively through several additional countries in South and Central
      America and the Caribbean. Simultaneously, several of these countries have seen a
      dramatic increase in the incidence of infants born with microcephaly. The rapid
      spread of Zika virus through the Americas, together with the association of
      infection with microcephaly and Guillain-Barre syndrome, has resulted in the
      World Health Organization declaring a public health emergency. Zika virus has the
      potential to spread to new areas where the Aedes mosquito vector is present and
      therefore presents a risk to the United States. This concise review describes the
      clinical features of Zika virus infection and provides advice for clinicians on
      counseling travelers and others about the disease. 

PMID- 27046525
TI  - Future Directions in Pain Management: Integrating Anatomically Selective Delivery
      Techniques With Novel Molecularly Selective Agents.
AB  - Treatment for chronic, locoregional pain ranks among the most prevalent unmet
      medical needs. The failure of systemic analgesic drugs, such as opioids, is often
      due to their off-target toxicity, development of tolerance, and abuse potential.
      Interventional pain procedures provide target specificity but lack
      pharmacologically selective agents with long-term efficacy. Gene therapy vectors
      are a new tool for the development of molecularly selective pain therapies, which
      have already been proved to provide durable analgesia in preclinical models.
      Taken together, advances in image-guided delivery and gene therapy may lead to a
      new class of dual selective analgesic treatments integrating the molecular
      selectivity of analgesic genes with the anatomic selectivity of interventional
      delivery techniques. 

PMID- 27046526
TI  - Running and Mortality: Is More Actually Worse?

PMID- 27046527
TI  - Factors Affecting Burnout in Physicians.

PMID- 27046528
TI  - Spontaneous Bacterial Empyema: Its Association With Liver Disease.

PMID- 27046529
TI  - Burnout and the Ethos of Medical Practice.

PMID- 27046530
TI  - Less Sitting, More Physical Activity, and Higher Cardiorespiratory Fitness:
      Associations With Weight Status.

PMID- 27046531
TI  - Improving Communication Skills and Professionalism Among General Surgery
      Residents, One Page at a Time.

PMID- 27046532
TI  - Disseminated Fusarium fungemia in a Patient With Acute Myeloid Leukemia.

PMID- 27046533
TI  - Man With Fever and Severe Diarrhea.

PMID- 27046535
TI  - Solvothermal synthesis of wire-like SnxSb2Te3+x with an enhanced thermoelectric
      performance.
AB  - Nanostructured tellurides have attracted increasing attention in thermoelectric
      applications for waste heat recovery and cooling devices. Here, we report on the
      synthesis of wire-like SnxSb2Te3+x (x = 0, 0.02 and 0.05) nanoparticles using
      elemental precursors in EG. The enhanced thermoelectric performance was achieved
      in alloyed samples due to the increase of carrier population in heavy valence
      band valleys by incorporating Sn(2+) at the Sb(3+) sublattice, enabling the
      simultaneous realization of low electrical resistivity along with a high Seebeck
      coefficient as well as the decline of thermal conductivity. Thus a boosted power
      factor and low thermal conductivity lead to the highest ZT value of 0.58 at 150 
      degrees C in the Sn0.02Sb2Te3.02 sample. Our research offers a general wet
      chemical route for the preparation of one-dimensional nanomaterials and probably
      promotes the practical thermoelectric applications of Sb2Te3-based materials at
      low temperatures.

PMID- 27046537
TI  - Atypical Fibroxanthoma in a 13-Year-Old Guatemalan Girl with Xeroderma
      Pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease involving a
      defect in DNA repair leading to the premature development of numerous aggressive
      cutaneous malignancies. Although atypical fibroxanthoma (AFX) is a neoplasm
      typically found in the setting of extensive sun exposure or therapeutic
      radiation, AFXs are rarely associated with children with XP. We report the case
      of a 13-year-old Guatemalan girl with the XP type C variant who developed one of
      the largest AFXs reported on a child's finger. 

PMID- 27046536
TI  - T-box3 is a ciliary protein and regulates stability of the Gli3 transcription
      factor to control digit number.
AB  - Crucial roles for T-box3 in development are evident by severe limb malformations
      and other birth defects caused by T-box3 mutations in humans. Mechanisms whereby
      T-box3 regulates limb development are poorly understood. We discovered
      requirements for T-box at multiple stages of mouse limb development and distinct
      molecular functions in different tissue compartments. Early loss of T-box3
      disrupts limb initiation, causing limb defects that phenocopy Sonic Hedgehog
      (Shh) mutants. Later ablation of T-box3 in posterior limb mesenchyme causes digit
      loss. In contrast, loss of anterior T-box3 results in preaxial polydactyly, as
      seen with dysfunction of primary cilia or Gli3-repressor. Remarkably, T-box3 is
      present in primary cilia where it colocalizes with Gli3. T-box3 interacts with
      Kif7 and is required for normal stoichiometry and function of a Kif7/Sufu complex
      that regulates Gli3 stability and processing. Thus, T-box3 controls digit number
      upstream of Shh-dependent (posterior mesenchyme) and Shh-independent, cilium
      based (anterior mesenchyme) Hedgehog pathway function. 

PMID- 27046538
TI  - The root of the problem: Occurrence of typical and atypical periapical pathoses.
AB  - BACKGROUND: A preponderance of periapical radiolucencies are of inflammatory
      etiology (radicular cysts or periapical granulomas) secondary to pulpal disease.
      In some instances, however, a suspected periapical inflammatory lesion is not a
      consequence of pulpal disease but instead represents a lesion of noninflammatory
      origin. The differential diagnosis for such lesions is broad, ranging from
      odontogenic cysts and tumors to metastatic disease. As the biological behavior of
      such lesions is varied, the distinction between inflammatory odontogenic
      periapical lesions and lesions of noninflammatory origin in a periapical location
      is critical. METHODS: A retrospective study of 5,993 archival periapical biopsies
      over a span of 15 years from the database of the Oral Pathology Biopsy Service in
      the Henry M. Goldman School of Dental Medicine at Boston University recorded the
      incidence of various lesions in a periapical location. RESULTS: Of the cases
      studied, 97.2% represented lesions of inflammatory origin with histopathologic
      diagnoses as follows: periapical granuloma (60.0%), radicular cyst (36.7%),
      periapical fibrous scar (0.27 %), and periapical abscess (0.23 %). The remaining
      2.8% cases were lesions of noninflammatory origin with histopathologic diagnoses
      of odontogenic keratocyst (also known as keratocystic odontogenic tumor), benign
      fibro-osseous lesions, and ameloblastoma. One patient had Langerhans cell
      disease, and 1 had central giant cell granuloma. CONCLUSIONS: Although most
      periapical specimens biopsied represented expected inflammatory periapical
      lesions, the biological behavior of underdiagnosed lesions may have considerable
      consequences for both the patient and the clinician. PRACTICAL IMPLICATIONS: This
      article serves to inform clinicians regarding the diversity of lesions arising in
      the periapical region of the jaws, to assist in the formulation of differential
      diagnoses, and to highlight the importance of submission of lesional tissue for
      histopathologic evaluation and definitive diagnosis when biopsy is clinically
      indicated.

PMID- 27046539
TI  - Risk Factors for Suicidal Ideation in Patients Feeling Severely Affected by
      Multiple Sclerosis.
AB  - BACKGROUND: Being severely affected by multiple sclerosis (MS) brings substantial
      physical and psychological challenges. Contrary to common thinking that MS is not
      lethal, there is a higher mortality risk in patients also reflected in alarming
      rates of assisted suicide, and - where possible - euthanasia. OBJECTIVE:
      Analyzing independent variables promoting suicidal ideation in severely affected
      MS patients. DESIGN: A self-report questionnaire with 25 needs categories
      including one self-assessment item "prone to suicidal ideation" was applied.
      SETTING/SUBJECTS: Included were patients reporting feeling subjectively severely
      affected by MS. Of 867 patients addressed, 573 (66.1%) completed the
      questionnaires. MEASUREMENTS: 32 items being potential risk factors for suicidal
      ideation were tested for statistical significance using a multivariate logistic
      regression model with stepwise, backward elimination procedure. RESULTS: 22.1% of
      573 patients (median age 51, range 20-83) had suicidal ideation. 48.4% suffered
      from secondary progressive, 24.7% from relapsing-remitting and 21.9% from primary
      progressive MS. A set of six statistically significant criteria for suicidal
      ideation were found. Three items were risk factors for suicidal ideation: the
      extent to which MS affects leisure time (p < 0.001), depression (p < 0.000), and
      feeling socially excluded (p < 0.002). Three items reduced the odds of suicidal
      ideation: having a purpose in life (p < 0.000), being productive (p < 0.000), and
      having comfort in faith and spiritual beliefs (p < 0.024). CONCLUSION: This study
      identified potentially modifiable factors that may help preventing suicide in
      people with MS. Integrating palliative care (PC) with its multidisciplinary
      approach could be beneficial to reduce patient's burden.

PMID- 27046540
TI  - Narrow band perfect absorber for maximum localized magnetic and electric field
      enhancement and sensing applications.
AB  - Plasmonics offer an exciting way to mediate the interaction between light and
      matter, allowing strong field enhancement and confinement, large absorption and
      scattering at resonance. However, simultaneous realization of ultra-narrow band
      perfect absorption and electromagnetic field enhancement is challenging due to
      the intrinsic high optical losses and radiative damping in metals. Here, we
      propose an all-metal plasmonic absorber with an absorption bandwidth less than 8
      nm and polarization insensitive absorptivity exceeding 99%. Unlike traditional
      Metal-Dielectric-Metal configurations, we demonstrate that the narrowband perfect
      absorption and field enhancement are ascribed to the vertical gap plasmonic mode
      in the deep subwavelength scale, which has a high quality factor of 120 and mode
      volume of about 10(-4) * (lambdares/n)(3). Based on the coupled mode theory, we
      verify that the diluted field enhancement is proportional to the absorption, and
      thus perfect absorption is critical to maximum field enhancement. In addition,
      the proposed perfect absorber can be operated as a refractive index sensor with a
      sensitivity of 885 nm/RIU and figure of merit as high as 110. It provides a new
      design strategy for narrow band perfect absorption and local field enhancement,
      and has potential applications in biosensors, filters and nonlinear optics. 

PMID- 27046541
TI  - Healthy Aging in Community for Older Lesbians.
AB  - PURPOSE: In Boston and Outer Cape, Massachusetts, we explored the expectations of
      lesbians 60 years and older regarding healthy aging and community importance.
      METHODS: Focus groups were conducted with participants after completing an
      anonymous demographic questionnaire. Thematic analysis was used to generate
      themes and identify how they varied by urban versus rural settings. RESULTS:
      Group discussions focused on community, finances, housing, and healthcare.
      Primary concerns included continued access to supportive and lesbian communities
      as a source of resilience during aging. CONCLUSION: Concerns about discrimination
      and isolation mirror themes found in national research. The study findings
      suggest a need for more research into the housing and transportation needs of
      lesbians approaching later life, with a focus on how those needs relate to
      affordability, accessibility, and proximity to social support and healthcare.
      These findings also suggest the need for substantial investments in strengthening
      the LGBT-related cultural competence of providers of services for the elderly.

PMID- 27046542
TI  - The impact of early human data on clinical development: there is time to win.
AB  - Modern accelerator mass spectrometry (AMS) methods enable the routine application
      of this technology in drug development. By the administration of a (14)C-labelled
      microdose or microtrace, pharmacokinetic (PK) data, such as mass balance,
      metabolite profiling, and absolute bioavailability (AB) data, can be generated
      easier, faster, and at lower costs. Here, we emphasize the advances and impact of
      this technology for pharmaceutical companies. The availability of accurate
      intravenous (iv) PK and human absorption, distribution, metabolism, and excretion
      (ADME) information, even before or during Phase I trials, can improve the
      clinical development plan. Moreover, applying the microtrace approach during
      early clinical development might impact the number of clinical pharmacology and
      preclinical safety pharmacology studies required, and shorten the overall drug
      discovery program.

PMID- 27046543
TI  - Developing Modularized Virtual Reality Simulators for Natural Orifice
      Translumenal Endoscopic Surgery (NOTES).
AB  - Natural orifice translumenal endoscopic surgery (NOTES) procedures are rapidly
      being developed in diverse surgical fields. We are developing a Virtual
      Translumenal Endoscopic Surgery Trainer (VTESTTM) built on a modularized platform
      that facilitates rapid development of virtual reality (VR) NOTES simulators. Both
      the hardware interface and software components consist of independent reusable
      and customizable modules. The developed modules are integrated to build a VR
      NOTES simulator for training in the hybrid transvaginal NOTES cholecystectomy.
      The simulator was demonstrated and evaluated by expert NOTES surgeons at the 2015
      Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) summit.

PMID- 27046544
TI  - Development of a Web-Based 3D Module for Enhanced Neuroanatomy Education.
AB  - Neuroanatomy is a challenging subject, with novice medical students often
      experiencing difficulty grasping the intricate 3D spatial relationships. Most of
      the anatomical teaching in undergraduate medicine utilizes conventional 2D
      resources. E-learning technologies facilitate the development of learner-centered
      educational tools that can be tailored to meet each student's educational needs,
      and may foster improved learning in neuroanatomy, however this has yet to be
      examined fully in the literature. An interactive 3D e-learning module was
      developed to complement gross anatomy laboratory instruction. Incorporating such
      3D modules may provide additional support for students in areas of anatomy that
      are spatially challenging, such as neuroanatomy. Specific anatomical structures
      and their relative spatial positions to other structures can be clearly defined
      in the 3D virtual environment from viewpoints that may not readily be available
      using cadaveric or 2D image modalities. Providing an interactive user interface
      for the 3D module in which the student controls many factors may enable the
      student to develop an improved understanding of the spatial relationships. This
      work outlines the process for the development of a 3D interactive module of the
      cerebral structures included in the anatomy curriculum for undergraduate medical
      students in their second year of study. 

PMID- 27046545
TI  - Avoiding Focus Shifts in Surgical Telementoring Using an Augmented Reality
      Transparent Display.
AB  - Conventional surgical telementoring systems require the trainee to shift focus
      away from the operating field to a nearby monitor to receive mentor guidance.
      This paper presents the next generation of telementoring systems. Our system,
      STAR (System for Telementoring with Augmented Reality) avoids focus shifts by
      placing mentor annotations directly into the trainee's field of view using
      augmented reality transparent display technology. This prototype was tested with
      pre-medical and medical students. Experiments were conducted where participants
      were asked to identify precise operating field locations communicated to them
      using either STAR or a conventional telementoring system. STAR was shown to
      improve accuracy and to reduce focus shifts. The initial STAR prototype only
      provides an approximate transparent display effect, without visual continuity
      between the display and the surrounding area. The current version of our
      transparent display provides visual continuity by showing the geometry and color
      of the operating field from the trainee's viewpoint. 

PMID- 27046546
TI  - Effects of an Avatar-Based Anti-Smoking Game on Smoking Cessation Intent.
AB  - The purpose of this study was to compare the effects of a computer-based anti
      smoking game on the intent and motivation to quit tobacco. Smokers with nicotine
      dependence were briefly exposed to an anti-smoking game with or without an avatar
      resembling the smoker's self. The computer-based anti-smoking game improved
      participants' immediate intent and motivation to quit smoking. Embedding an
      avatar resembling self into the game did not result in added benefits. 

PMID- 27046547
TI  - A Unified Framework for Haptic Interaction in Multimodal Virtual Environments.
AB  - In this paper we introduce a Modified Iterative Constraint Anticipation (MICA)
      method that provides a unified framework for direct and response-based indirect
      haptic interaction common in many interactive virtual environments. Collision
      constraints during response based interaction that are modeled using the linear
      complementarity problem (LCP) framework resolves collision constraints from
      response-based interactions while allowing for accurate computation of reaction
      forces. Direct user manipulation is enabled by the linear projection constraints
      (LPC). A smoothing filter is used to post-process the reaction forces arising
      from both LCP and LPC to achieve stable interactions in real-time. The
      effectiveness of MICA is demonstrated using example problems involving deformable
      bodies. 

PMID- 27046548
TI  - An Approach for Automated Scene Management in Real-Time Medical Simulation
      Framework.
AB  - In this paper we present an algorithm that allows for minimal end-user inputs by
      internally automating the creation and management of interactions amongst the
      objects in the scene in real-time medical simulation framework. A bi-directed
      graph (with nodes representing the scene objects and the connections representing
      the interactions) is formed based on the inputs from the user. This graph is then
      processed using a two stage algorithm that aims to find subgraphs that can be
      treated as independent sub-systems. Collision detection, collision response,
      assembly and solver objects are then automatically created and managed. This
      allows for users with limited knowledge of the underlying physics models,
      collision detection and contact algorithms to easily create a surgical scenario
      with minimal inputs. 

PMID- 27046549
TI  - An Examination of Metrics for a Simulated Ventriculostomy Part-Task.
AB  - As one of the most commonly performed neurosurgical procedures, ventriculostomy
      training simulators are becoming increasingly familiar features in research
      institutes and teaching facilities. Despite their widespread implementations and
      adoption, simulators to date have not fully explored the landscape of performance
      metrics that reflect surgical proficiency. They opt instead for measures that are
      qualitative or simple to compute and conceptualize. In this paper, we examine and
      compare the use of various metrics to characterize the performance of users on
      simulated part-task ventriculostomy scenarios derived from patient data. As an
      initial study, we examine how our metrics relate to expert classification of
      scenario difficulty as well as measures of anatomical variation. 

PMID- 27046550
TI  - Assessment of Haptic Interaction for Home-Based Physical Tele-Therapy using
      Wearable Devices and Depth Sensors.
AB  - In this paper a prototype system is presented for home-based physical tele
      therapy using a wearable device for haptic feedback. The haptic feedback is
      generated as a sequence of vibratory cues from 8 vibrator motors equally spaced
      along an elastic wearable band. The motors guide the patients' movement as they
      perform a prescribed exercise routine in a way that replaces the physical
      therapists' haptic guidance in an unsupervised or remotely supervised home-based
      therapy session. A pilot study of 25 human subjects was performed that focused
      on: a) testing the capability of the system to guide the users in arbitrary
      motion paths in the space and b) comparing the motion of the users during typical
      physical therapy exercises with and without haptic-based guidance. The results
      demonstrate the efficacy of the proposed system. 

PMID- 27046551
TI  - Accelerating Surgical Simulation Development via OpenSurgSim: Burr Hole Trainer.
AB  - The first complete simulation based on OpenSurgSim (OSS) is used as a case study
      for analyzing how the toolkit can accelerate the development of surgical
      simulations. The Burr Hole Trainer (BHT) is designed to train non-neurosurgeons
      to drill holes in the skull to relieve intracranial pressure, and the majority of
      its simulation functionality is provided by OSS. Based on code size, using OSS
      cut the development time in half, reduced the necessary size of the development
      team by two-thirds, and saved millions of US dollars. 

PMID- 27046552
TI  - 3D Perception Technologies for Surgical Operating Theatres.
AB  - 3D Perception technologies have been explored in various fields. This paper
      explores the application of such technologies for surgical operating theatres.
      Clinical applications can be found in workflow detection, tracking and analysis,
      collision avoidance with medical robots, perception of interaction between
      participants of the operation, training of the operation room crew, patient
      calibration and many more. In this paper a complete perception solution for the
      operating room is shown. The system is based on the ToF technology integrated to
      the Microsoft Kinect One implements a multi camera approach. Special emphasize is
      put on the tracking of the personnel and the evaluation of the system performance
      and accuracy. 

PMID- 27046553
TI  - SafeHOME: Promoting Safe Transitions to the Home.
AB  - This paper introduces the SafeHome Simulator system, a set of immersive Virtual
      Reality Training tools and display systems to train patients in safe discharge
      procedures in captured environments of their actual houses. The aim is to lower
      patient readmission by significantly improving discharge planning and training.
      The SafeHOME Simulator is a project currently under review. 

PMID- 27046554
TI  - Immersive Learning Experiences for Surgical Procedures.
AB  - This paper introduces a computer-based system that is designed to record a
      surgical procedure with multiple depth cameras and reconstruct in three
      dimensions the dynamic geometry of the actions and events that occur during the
      procedure. The resulting 3D-plus-time data takes the form of dynamic, textured
      geometry and can be immersively examined at a later time; equipped with a Virtual
      Reality headset such as Oculus Rift DK2, a user can walk around the
      reconstruction of the procedure room while controlling playback of the recorded
      surgical procedure with simple VCR-like controls (play, pause, rewind, fast
      forward). The reconstruction can be annotated in space and time to provide more
      information of the scene to users. We expect such a system to be useful in
      applications such as training of medical students and nurses. 

PMID- 27046555
TI  - Synthesis and Simulation of Surgical Process Models.
AB  - Virtual Reality for surgical training is mainly focused on technical surgical
      skills. We work on providing a novel approach to the use of Virtual Reality
      focusing on the procedural aspects. Our system relies on a specific work-flow
      generating a model of the procedure from real case surgery observation in the
      operating room. This article presents the different technologies created in the
      context of our project and their relations as other components of our workflow. 

PMID- 27046556
TI  - Computer Imagery and Neurological Rehabilitation: On the Use of Augmented Reality
      in Sensorimotor Training to Step Up Naturally Occurring Cortical Reorganization
      in Patients Following Stroke.
AB  - This work promotes the use of computer-generated imagery -as visual illusions- to
      speed up motor learning in rehabilitation. In support of this, we adhere the
      principles of experience-dependent neuroplasticity and the positive impact of
      virtual reality (VR) thereof. Specifically, post-stroke patients will undergo
      motor therapy with a surrogate virtual limb that fakes the paralyzed limb. Along
      these lines, their motor intentions will match the visual evidence, which fosters
      physiological, functional and structural changes over time, for recovery of lost
      function in an injured brain. How we make up such an illusion using computer
      graphics, is central to this paper. 

PMID- 27046557
TI  - Development of a Soft Tissue Elastography Robotic Arm (STiERA).
AB  - High fidelity surgical simulations must rely upon accurate soft tissue models to
      ensure realism of the simulations. Simulating multi-layer tissue becomes
      increasingly complex due to the specific mechanical properties of each individual
      layer. We have developed a Soft Tissue Elastography Robotic Arm (STiERA) system
      capable of identifying layer specific properties of multi-layer constructs while
      maintaining the integrity of each layer. The system was validated using tissue
      mimicking agar gel phantoms and showed great promise by identifying the layer
      specific properties with accuracy of greater than 80% when compared to known
      ground truth values from a commercial material testing system. 

PMID- 27046558
TI  - Videolaryngoscopy Simulator: New Technology Leads to New Training Challenges.
AB  - A videolaryngoscope is a more advanced tool than a traditional laryngoscope that
      eases endotracheal intubation by visualizing the vocal cords with a camera on the
      tip of the blade. However, using a videolaryngoscope can present difficulty in
      passing the tube into the glottic opening in some patients. This study developed
      a training protocol for intubation with videolaryngoscope and trained 22
      anesthesia residents. A Parametrically Adjustable Airway Mannequin (PAAM) was set
      to provide easy and difficult configurations. Motion data of the
      videolaryngoscope, stylet, mannequin head, and hyoid bone were captured with 6
      axis magnetic position sensors, along with the video image. The time to complete
      the various components of the task were recorded and used as an indication of
      competence along with observation by experts. The validity of the mannequin was
      supported by data that showed that the difficult configuration of PAAM took
      longer to intubate than the easy configuration (66 vs. 39 seconds during pre
      test). The effectiveness of the training protocol was supported by improvement in
      trainee performance. At the beginning of the training, intubation with the
      difficult configuration took an average of 66 seconds, immediately after training
      it averaged 23 seconds, and in retention tests over a month after the training
      the average duration was 33 seconds. 

PMID- 27046559
TI  - Virtual Airway Skills Trainer (VAST) Simulator.
AB  - This paper presents a simulation of Virtual Airway Skill Trainer (VAST) tasks.
      The simulated tasks are a part of two main airway management techniques;
      Endotracheal Intubation (ETI) and Cricothyroidotomy (CCT). ETI is a simple
      nonsurgical airway management technique, while CCT is the extreme surgical
      alternative to secure the airway of a patient. We developed identification of
      Mallampati class, finding the optimal angle for positioning pharyngeal/mouth axes
      tasks for ETI and identification of anatomical landmarks and incision tasks for
      CCT. Both ETI and CCT simulators were used to get physicians' feedback at Society
      for Education in Anesthesiology and Association for Surgical Education spring
      meetings. In this preliminary validation study, total 38 participants for ETI and
      48 for CCT performed each simulation task and completed pre and post
      questionnaires. In this work, we present the details of the simulation for the
      tasks and also the analysis of the collected data from the validation study. 

PMID- 27046560
TI  - Personalized Guides for Registration in Surgical Navigation.
AB  - Personalized guides are increasingly used in orthopedic procedures but do not
      provide for intraoperative re-planning. This work presents a tracked guide that
      used physical registration to provide an anatomy-to-tracking coordinate frame
      transformation for surgical navigation. In a study using seven femoral models
      derived from clinical CT scans used for hip resurfacing, a guide characterization
      FRE of 0.4 degrees +/-0.2 degrees , drill-path drill-path angular TRE of 0.9
      degrees +/-0.4 degrees  and a positional TRE of 1.2mm+/-0.4mm were found; these
      values are comparable to conventional optical tracking accuracy. This novel use
      of a tracked guide may be particularly applicable to procedures that require a
      small surgical exposure, or when operating on anatomical regions with small bones
      that are difficult to track or reliably register. 

PMID- 27046561
TI  - Towards surgeon-authored VR training: the scene-development cycle.
AB  - Enabling surgeon-educators to themselves create virtual reality (VR) training
      units promises greater variety, specialization, and relevance of the units. This
      paper describes a software bridge that semi-automates the scene-generation cycle,
      a key bottleneck in authoring, modeling, and developing VR units. Augmenting an
      open source modeling environment with physical behavior attachment and collision
      specifications yields single-click testing of the full force-feedback enabled
      anatomical scene. 

PMID- 27046562
TI  - Does Virtual Haptic Dissection Improve Student Learning? A Multi-Year Comparative
      Study.
AB  - This study investigated the haptic 'dissection' of a digital model of the hand
      and wrist in anatomy education at both undergraduate (UG) and postgraduate (PG)
      levels. The study ran over five successive years and was split into three
      discreet phases. Phase one compared the results of PG students across control,
      non-haptic and haptic groups. Phase two compared the results of UG students
      between control and haptic groups. Phase three compared the results of UG
      students across control, non-haptic and haptic groups. Results for all phases
      indicate that use of the model, both through haptic and non-haptic interfaces
      produced some significantly improved test results. The non-haptic group
      performing the strongest overall indicating that the addition of haptic feedback
      may not be beneficial to student learning. 

PMID- 27046563
TI  - Towards the Implementation of an Autonomous Camera Algorithm on the da Vinci
      Platform.
AB  - Camera positioning is critical for all telerobotic surgical systems. Inadequate
      visualization of the remote site can lead to serious errors that can jeopardize
      the patient. An autonomous camera algorithm has been developed on a medical robot
      (da Vinci) simulator. It is found to be robust in key scenarios of operation.
      This system behaves with predictable and expected actions for the camera arm with
      respect to the tool positions. The implementation of this system is described
      herein. The simulation closely models the methodology needed to implement
      autonomous camera control in a real hardware system. The camera control algorithm
      follows three rules: (1) keep the view centered on the tools, (2) keep the zoom
      level optimized such that the tools never leave the field of view, and (3) avoid
      unnecessary movement of the camera that may distract/disorient the surgeon. Our
      future work will apply this algorithm to the real da Vinci hardware. 

PMID- 27046564
TI  - Evaluation of RGP Contact Lens Fitting in Keratoconus Patients Using Hierarchical
      Fuzzy Model and Genetic Algorithms.
AB  - Keratoconus is a progressive non-inflammatory disease of the cornea. Rigid gas
      permeable contact lenses (RGPs) are prescribed when the disease progresses.
      Contact lens fitting and assessment is very difficult in these patients and is a
      concern of ophthalmologists and optometrists. In this study, a hierarchical fuzzy
      system is used to capture the expertise of experienced ophthalmologists during
      the lens evaluation phase of prescription. The system is fine-tuned using genetic
      algorithms. Sensitivity, specificity and accuracy of the final system are 88.9%,
      94.4% and 92.6% respectively. 

PMID- 27046565
TI  - Evaluation of Software Tools for Segmentation of Temporal Bone Anatomy.
AB  - Surgeons are increasingly relying on 3D medical image data for planning
      interventions. Virtual 3D models of intricate anatomy, such as that found within
      the temporal bone, have proven useful for surgical education, planning, and
      rehearsal, but such applications require segmentation of surgically relevant
      structures in the image data. Four publicly available software packages, ITK
      SNAP, MITK, 3D Slicer, and Seg3D, were evaluated for their efficacy in segmenting
      temporal bone anatomy from CT and MR images to support patient-specific surgery
      simulation. No single application provided efficient means to segment every
      structure, but a combination of the tools evaluated enables creation of a
      complete virtual temporal bone model from raw image data with reasonably minimal
      effort. 

PMID- 27046566
TI  - A Cost-Effective Virtual Environment for Simulating and Training Powered
      Wheelchairs Manoeuvres.
AB  - Control of a powered wheelchair is often not intuitive, making training of new
      users a challenging and sometimes hazardous task. Collisions, due to a lack of
      experience can result in injury for the user and other individuals. By conducting
      training activities in virtual reality (VR), we can potentially improve driving
      skills whilst avoiding the risks inherent to the real world. However, until
      recently VR technology has been expensive and limited the commercial feasibility
      of a general training solution. We describe Wheelchair-Rift, a cost effective
      prototype simulator that makes use of the Oculus Rift head mounted display and
      the Leap Motion hand tracking device. It has been assessed for face validity by a
      panel of experts from a local Posture and Mobility Service. Initial results augur
      well for our cost-effective training solution. 

PMID- 27046567
TI  - Effects of Hand Dominance and Postural Selection on Muscle Activities of Virtual
      Laparoscopic Surgical Training Tasks.
AB  - This study investigated how the ergonomic factors, such as hand dominance and
      postural selection, influenced on surgical performance regarding the changes of
      muscle activity. Twenty novices performed two virtual laparoscopic surgical
      training tasks and five target muscle activities were measured. Compared with
      using dominant hand, surgical skills performance using non-dominant hand
      increased muscle activities. Muscle fatigue is more likely induced in standing
      position than sitting position during practice. This study suggests an emerging
      need to focus on hand dominance during laparoscopic surgical training to address
      the impact of hand discrepancy on bimanual coordination. It is also important to
      pay attention on postural selection during training to reduce muscle fatigue,
      which possibly leads to injuries. 

PMID- 27046568
TI  - Perturbed Communication in a Virtual Environment to Train Medical Team Leaders.
AB  - The VICTEAMS project aims at designing a virtual environment for training medical
      team leaders to non-technical skills. The virtual environment is populated with
      autonomous virtual agents who are able to make mistakes (in action or
      communication) in order to train rescue team leaders and to make them adaptive
      with all kinds of situations or teams. 

PMID- 27046569
TI  - Normal Brain-Skull Development with Hybrid Deformable VR Models Simulation.
AB  - This paper describes a simulation framework for a clinical application involving
      skull-brain co-development in infants, leading to a platform for craniosynostosis
      modeling. Craniosynostosis occurs when one or more sutures are fused early in
      life, resulting in an abnormal skull shape. Surgery is required to reopen the
      suture and reduce intracranial pressure, but is difficult without any predictive
      model to assist surgical planning. We aim to study normal brain-skull growth by
      computer simulation, which requires a head model and appropriate mathematical
      methods for brain and skull growth respectively. On the basis of our previous
      model, we further specified suture model into fibrous and cartilaginous sutures
      and develop algorithm for skull extension. We evaluate the resulting simulation
      by comparison with datasets of cases and normal growth. 

PMID- 27046570
TI  - A Virtual Reality Game for Chronic Pain Management: A Randomized, Controlled
      Clinical Study.
AB  - Although Virtual Reality (VR) applications have been shown to reduce many forms
      of acute pain, such research of VR applications and their effects on chronic pain
      is still at its infancy. In this study, we designed a VR game Cryoslide, and
      examined its analgesic effect on chronic pain patients, its end users, in a
      clinical setting. In this randomized, controlled crossover clinical study of 20
      chronic pain patients, Cryoslide significantly reduced perceived pain compared to
      the baseline and the control group. The results demonstrate that Cryoslide can be
      effectively used as an analgesic intervention for chronic pain management to
      lessen pain intensity during short-term symptom spikes. 

PMID- 27046571
TI  - Development of a Generic Tubular Tree Structure for the Modeling of Orbital
      Cranial Nerves.
AB  - We developed a generic approach for modeling tubular tree structures as triangle
      meshes for the extension of our biomechanical eye model SEE-KID with a
      visualization of the orbital cranial nerves. Since three of the orbital nerves
      innervate extraocular eye muscles and move together with them, the structure must
      also support the partial translation and rotation of the nerves. For the SEE-KID
      model, this extension allows a better parameterization as well as an easier
      simulation of innervational disorders. Moreover, it makes the model even more
      useful for education and training purposes in contrast to other anatomical
      models. Due to its generic nature, the developed data structure and the
      associated algorithms can be used for any tubular tree structures, even in non
      medical application areas. 

PMID- 27046572
TI  - Automated Tracking and Quantification of Autistic Behavioral Symptoms Using
      Microsoft Kinect.
AB  - The prevalence of autism spectrum disorder (ASD) has risen significantly in the
      last ten years, and today, roughly 1 in 68 children has been diagnosed. One
      hallmark set of symptoms in this disorder are stereotypical motor movements.
      These repetitive movements may include spinning, body-rocking, or hand-flapping,
      amongst others. Despite the growing number of individuals affected by autism, an
      effective, accurate method of automatically quantifying such movements remains
      unavailable. This has negative implications for assessing the outcome of ASD
      intervention and drug studies. Here we present a novel approach to detecting
      autistic symptoms using the Microsoft Kinect v.2 to objectively and automatically
      quantify autistic body movements. The Kinect camera was used to film 12 actors
      performing three separate stereotypical motor movements each. Visual Gesture
      Builder (VGB) was implemented to analyze the skeletal structures in these
      recordings using a machine learning approach. In addition, movement detection was
      hard-coded in Matlab. Manual grading was used to confirm the validity and
      reliability of VGB and Matlab analysis. We found that both methods were able to
      detect autistic body movements with high probability. The machine learning
      approach yielded highest detection rates, supporting its use in automatically
      quantifying complex autistic behaviors with multi-dimensional input. 

PMID- 27046573
TI  - Measurement of Temperature Dependent Apparent Specific Heat Capacity in
      Electrosurgery.
AB  - This paper reports on the measurement of temperature dependent apparent specific
      heat of ex-vivo porcine liver tissue during radiofrequency alternating current
      heating for a large temperature range. The difference between spatial and
      temporal evolution of experimental temperature, obtained during electrosurgical
      heating by infrared thermometry, and predictions based on finite element modeling
      was minimized to obtain the apparent specific heat. The model was based on
      transient heat transfer with internal heat generation considering heat storage
      along with conduction. Such measurements are important to develop computational
      models for real time simulation of electrosurgical procedures. 

PMID- 27046574
TI  - Junctional and Inguinal Hemorrhage Simulation: Tourniquet Master Training.
AB  - Hemorrhages are the leading cause of potentially survivable combat mortalities
      when patients are unable to reach a treatment facility in time. New tourniquet
      devices have been developed to combat hemorrhages in the field. However, there is
      a lack in training systems to properly teach and assess users on tourniquet
      device application. We have developed an objective feedback system applicable to
      various full body manikins. We tested the system with expert users and received
      improvement feedback and verified the system's usefulness in instructing and
      assessing correct tourniquet device use. 

PMID- 27046575
TI  - The Impact of Structured Incentives on the Adoption of a Serious Game for Hand
      Hygiene Training in a Hospital Setting.
AB  - Hand hygiene is recognized by the CDC as the most effective method of preventing
      Hospital Acquired Infections (HAIs) which cost the US healthcare system $14
      Billion. However, training and promotion of hand hygiene in healthcare settings
      is an on-going challenge. This paper describes a hand hygiene improvement
      campaign in Edinburgh Royal Infirmary (Scotland, UK) using the SureWash gesture
      recognition system (SureWash, IRL). The campaign consisted of two phases of three
      months each; the first phase involved technology evaluation and familiarization
      in a variety of settings within the hospital. The second phase involved rotation
      between two units with specific changes to the incentives for completing the
      training. There were 2,010 individual training sessions with over 30% outside of
      office hours. Individuals completed an average of 2.72 training sessions each and
      90% of staff passed the assessment. Senior staff noted a change in hand hygiene
      culture following the campaign and the good-natured competition between staff to
      demonstrate hand hygiene competence using the SureWash serious game. While the
      new technology did facilitate the culture change its successful implementation
      was dependent on a set of incentives for staff and a structured implementation
      plan. 

PMID- 27046576
TI  - A Framework for Patient-Specific Spinal Intervention Simulation: Application to
      Lumbar Spinal Durotomy Repair.
AB  - We present a functional and patient-specific lumbar phantom for the training of
      spinal durotomy and dura closure under microscopic view, consisting of a lumbar
      model, pressurized dural surrogate, together immersed in a tissue-mimicking layer
      simulating fat, muscle and skin. The lumbar model was derived from a patient
      computed tomography scan, preserving the natural shape and curvature of the
      lumbar column. The inclusion of the simulated soft-tissue layer was critical for
      preserving the surgical ergonomics and presented a realistic view under the
      surgical microscope. As the success of dura repair is indicated by the watertight
      closure of the thecal sac, the dura surrogate was connected to a pressurized and
      closed-loop water system to provide functional cerebrospinal fluid leakage during
      durotomy. This functional phantom is inexpensive to construct, provides a
      realistic tactile and visual environment for spinal durotomy repair, and can be
      easily extended to simulate other patient-specific spinal interventions. 

PMID- 27046577
TI  - Fabric Force Sensors for the Clinical Breast Examination Simulator.
AB  - Sensor enabled simulators may help in training and assessing clinical skill.
      Their are imitations on the locations current sensors can be placed without
      interfering with the clinical examination. In this study novel fabric force
      sensors were developed and tested. These sensors are soft and flexible and
      undetectable when placed in different locations in the simulator. Five sensors
      were added to our current sensor enabled breast simulator. Eight participants
      performed the clinical breast examination on the simulator and documented their
      findings. There was a significant relationship for both clinical breast
      examination time (r(6) = 0.99, p < 0.001) and average force (r(6) = 0.92, p <
      0.005) between our current sensors and the new fabric sensors. In addition the
      senors were not noticed by the participants. These new sensors provide new
      methods to measure and assess clinical skill and performance. 

PMID- 27046578
TI  - A Simulator for Measuring Forces During Surgical Knots.
AB  - In this study new metrics were developed for assessing the performance of
      surgical knots. By adding sensors to a knot tying simulator we were able to
      measure the forces used while performing this basic and essential skill. Data
      were collected for both superficial tying and deep tying of square knots using
      the one hand and two hands techniques. Participants used significantly more force
      when tying a deep knot compared to a superficial knot (3.79N and 1.6N
      respectively). Different patterns for upward and downward forces were identified
      and showed that although most of the time upward forces are used (72% of the
      time), the downward forces are just as large. These data can be crucial for
      improving the safeness of knot tying. Combing these metrics with known metrics
      based on knot tensiometry and motion data may help provide feedback and objective
      assessment of knot tying skills. 

PMID- 27046579
TI  - A Multi-Layered Needle Injection Simulator.
AB  - Insuring correct needle location is crucial in many medical procedures. This can
      be even more challenging for physicians injecting in a new location for the first
      time. Since they do not necessarily know how the tissue is supposed to feel,
      finding the correct location and correct depth can be difficult. In this study we
      designed a simulator for training needle injection. The simulator was fabricated
      to give a realistic feeling of injecting Botox(r) in the temporalis and the
      semispinalis muscles as part of migraine treatment. In addition the simulator
      provided real-time feedback of correct needle location. Nine residents and
      medical students evaluated the simulator. They made several errors that were
      corrected real time using the real time feedback provided. They found the
      simulator to be very useful and that the training significantly improved their
      confidence. The methods described in this study can easily be implemented for
      developing needle injection simulators for other anatomical locations. 

PMID- 27046580
TI  - The Evolution of Medical Training Simulation in the U.S. Military.
AB  - The United States has been at war since 2003. During that time, training using
      Medical Simulation technology has been developed and integrated into military
      medical training for combat medics, nurses and surgeons. Efforts stemming from
      the Joint Programmatic Committee-1 (JPC-1) Medical Simulation and Training
      Portfolio has allowed for the improvement and advancement in military medical
      training by focusing on research in simulation training technology in order to
      achieve this. Based upon lessons learned capability gaps have been identified
      concerning the necessity to validate and enhance combat medial training
      simulators. These capability gaps include 1) Open Source/Open Architecture; 2)
      Modularity and Interoperability; and 3) Material and Virtual Reality (VR) Models.
      Using the capability gaps, JPC-1 has identified important research endeavors that
      need to be explored. 

PMID- 27046581
TI  - Active and Passive Haptic Training Approaches in VR Laparoscopic Surgery
      Training.
AB  - Laparoscopic surgery has become a widely performed surgery as it is one of the
      most common minimally invasive surgeries. Doctors perform the surgery by
      manipulating thin and long surgical instruments precisely with the assistance of
      laparoscopic video with limited field of view. The power control of the
      instruments' tip is especially very important, because excessive power may damage
      internal organs. The training of this surgical technique is mainly supervised by
      an expert in hands-on coaching program. However, it is difficult for the experts
      to spend sufficient time for coaching. Therefore, we aim to teach the expert's
      hand movements in laparoscopic surgery to trainees using VR-based simulator,
      which is equipped with a guidance force display device. To realize the system, we
      propose two haptic training approaches for transferring the expert's hand
      movements to the trainee. One is active training, and the other is passive
      training. The former approach shows the expert's movements only when the trainee
      makes large errors while the latter shows the expert's movements continuously. In
      this study, we validate the applicability of these approaches through tasks in VR
      laparoscopic surgery training simulator, and identify the differences between
      these approaches. 

PMID- 27046582
TI  - Real-Time Ultrasound Simulation for Training of US-Guided Needle Insertion in
      Breathing Virtual Patients.
AB  - One draw-back of most existing VR ultrasound training simulators is the use of
      static 3D patient models neglecting physiological changes induced e.g. by
      respiration or heart motion. In this paper to the aim of more realistic
      Ultrasound simulation, breathing motion extracted from 4D CT image data is
      integrated into our visuo-haptic simulation framework. The simulated ultrasound
      images are used for the training of US-guided needle insertion procedures in
      liver surgery. The methodology developed enables US simulation, 3D visualization
      and haptic steering of the ultrasound probe and the needle in real-time in
      breathing virtual bodies. 

PMID- 27046583
TI  - The Effect of Optical Marker Configuration on Tracking Accuracy in Image Guided
      Surgery.
AB  - In this study, the effect of the geometrical configuration of retroreflective
      markers on the maximum tracking uncertainty of target points during a medical
      navigation is analyzed. Methods that help users select and set up an optimal
      configuration for minimizing the navigation uncertainty are proposed. The methods
      are evaluated by simulating surgical navigation environment using an optical
      tracking system. The result shows that the maximum uncertainty of tracking the
      target points lying outside the marker region is a function of the configuration
      of some of the associated markers and the precision of the optical tracking
      system used. We also show that the use of flexible rigid bodies minimizes target
      tracking uncertainty by enabling a customized reconfiguration of markers for
      optimal pose with respect to individual surgical target position during
      preoperative planning phase. 

PMID- 27046584
TI  - An Interactive 3D Virtual Anatomy Puzzle for Learning and Simulation - Initial
      Demonstration and Evaluation.
AB  - To inspire young students (grades 6-12) to become medical practitioners and
      biomedical engineers, it is necessary to expose them to key concepts of the field
      in a way that is both exciting and informative. Recent advances in medical image
      acquisition, manipulation, processing, visualization, and display have
      revolutionized the approach in which the human body and internal anatomy can be
      seen and studied. It is now possible to collect 3D, 4D, and 5D medical images of
      patient specific data, and display that data to the end user using consumer level
      3D stereoscopic display technology. Despite such advancements, traditional 2D
      modes of content presentation such as textbooks and slides are still the standard
      didactic equipment used to teach young students anatomy. More sophisticated
      methods of display can help to elucidate the complex 3D relationships between
      structures that are so often missed when viewing only 2D media, and can instill
      in students an appreciation for the interconnection between medicine and
      technology. Here we describe the design, implementation, and preliminary
      evaluation of a 3D virtual anatomy puzzle dedicated to helping users learn the
      anatomy of various organs and systems by manipulating 3D virtual data. The puzzle
      currently comprises several components of the human anatomy and can be easily
      extended to include additional organs and systems. The 3D virtual anatomy puzzle
      game was implemented and piloted using three display paradigms - a traditional 2D
      monitor, a 3D TV with active shutter glass, and the DK2 version Oculus Rift, as
      well as two different user interaction devices - a space mouse and traditional
      keyboard controls. 

PMID- 27046585
TI  - Wearable Ultrasound Array for Point-of-Care Imaging and Patient Monitoring.
AB  - A versatile, flexible piezoceramic array has been developed for a variety of
      ultrasound applications. The transducer can be configured as a linear or
      curvilinear transducer array, or mounted directly onto the body as a patch or
      wearable device. Results using a prototype 16-element array demonstrated
      equivalence to commercial linear array probes in accuracy of vessel diameter
      measurements in vascular phantoms. The ability to view needle insertion for
      peripherally inserted central catheter (PICC) procedures was also demonstrated.
      Opportunities for wearable ultrasound devices include point-of-care imaging,
      combat casualty care, ultrasound therapy, patient monitoring, and personal
      health. 

PMID- 27046586
TI  - Hybrid Rendering Architecture for Realtime and Photorealistic Simulation of Robot
      Assisted Surgery.
AB  - In this paper we present a method for combining realtime and non-realtime
      (photorealistic) rendering with open source software. Realtime rendering provides
      sufficient realism and is a good choice for most simulation and regression
      testing purposes in robot-assisted surgery. However, for proper end-to-end
      testing of the system, some computer vision algorithms require high fidelity
      images that capture more minute details of the real scene. One of the central
      practical obstacles to combining both worlds in a uniform way is creating models
      that are suitable for both kinds of rendering paradigms. We build a modeling
      pipeline using open source tools that builds on established, open standards for
      data exchange. The result is demonstrated through a unified model of the medical
      OpenHELP phantom used in the Gazebo robotics simulator, which can at the same
      time be rendered with more visual fidelity in the Cycles raytracer. 

PMID- 27046587
TI  - Development and Evaluation of a Novel Pan-Specialty Virtual Reality Surgical
      Simulator for Smartphones.
AB  - Touch Surgery is a novel simulator that allows cognitive task simulation and
      rehearsal of surgical procedures. Touch Surgery is designed for Apple and Android
      smartphones and tablets. This allows a global community of surgical professionals
      to review the steps of a procedure and test their competence. Content on Touch
      Surgery is developed with expert surgeons in the field from world leading
      institutions. Here we describe the development of Touch Surgery, its adoption by
      the global training community. 

PMID- 27046588
TI  - Objective Surgical Skill Differentiation for Physical and Virtual Surgical
      Trainers via Functional Near-Infrared Spectroscopy.
AB  - This study proposes a methodology to objectively differentiate surgical skill for
      physical and virtual trainers by measuring functional activation between expert
      and novice surgeons. Results indicate that there is a significant increase in
      functional activation for novices in the right lateral prefrontal cortex, and
      decrease in the left medial primary motor cortex, and the supplementary motor
      area for the physical trainer (p<0.05). Results also indicate that there is a
      significant lower functional activation for novices compared to experts in the
      left medial primary motor cortex for the virtual skills trainer (p<0.05). 

PMID- 27046589
TI  - Integrated Self-Management System for Improved Treatment of Asthma.
AB  - A mobile, affordable product that provides clinicians and patients with
      comprehensive asthma assessment is needed to improve asthma control. Our solution
      is an integrated system consisting of a portable, inexpensive, easy-to-use
      spirometer and a mobile application that communicates wirelessly with the
      spirometer. Results demonstrated that the wireless asthma management solution
      meets recommended American Thoracic Society (ATS) and European Respiratory
      Society (ERS) standards. The device is expected to empower patients to accurately
      self-assess their asthma for better self-management at home, work, or leisure. 

PMID- 27046590
TI  - Development of Haptic Needle for VR Based Injection Training System Using
      Simulated Patient.
AB  - VR based injection training system using standardized patient was proposed. This
      system uses haptic needle (HNSP) which can represent haptic force. Since the
      previously proposed system had a few problems with haptic reproduction,
      biological reproducibility needed to be improved. In order to solve these
      problems, we developed a new HNSP to replace the haptic needle. In addition, we
      conducted two validation studies for the HNSP. 

PMID- 27046591
TI  - Validation of an Objective Assessment Instrument for Non-Surgical Treatments of
      Chest Wall Deformities.
AB  - Depending on the severity of the condition and associated risk, surgical
      intervention may not always be the first choice. This is true for treating chest
      wall deformities such as pectus excavatum and pectus carinatum. For both
      conditions, novel non-surgical treatments have been developed to gradually
      alleviate the malformation making use of the elastic nature of the costal
      cartilages at an early age of the patient. To quantify the performance of such
      treatments, this paper introduces and discusses the development of a software
      based instrument that utilizes 3D chest optical images (surface scans) as input
      and uses registration techniques to produce an objective gauge of a patient's
      physical improvement after undergoing treatments. Further discussed is an
      experiment designed to investigate the construct validity of the developed
      instrument. 

PMID- 27046592
TI  - Hand VR Exergame for Occupational Health Care.
AB  - The widespread use and ubiquity of mobile computing technologies such as
      smartphones, tablets, laptops and portable gaming consoles has led to an increase
      in musculoskeletal disorders due to overuse, bad posture, repetitive movements,
      fixed postures and physical de-conditioning caused by low muscular demands while
      using (and over-using) these devices. In this paper we present the development of
      a hand motion-based virtual reality-based exergame for occupational health
      purposes that allows the user to perform simple exercises using a cost-effective
      non-invasive motion capture device to help overcome and prevent some of the
      muskoloskeletal problems associated with the over-use of keyboards and mobile
      devices. 

PMID- 27046593
TI  - Development and Analysis of Psychomotor Skills Metrics for Procedural Skills
      Decay.
AB  - In this paper we develop and analyze the metrics associated with a force
      production task involving a stationary target with the help of advanced VR and
      Force Dimension Omega 6 haptic device. We study the effects of force magnitude
      and direction on the various metrics namely path length, movement smoothness,
      velocity and acceleration patterns, reaction time and overall error in achieving
      the target. Data was collected from 47 participants who were residents. Results
      show a positive correlation between the maximum force applied and the deflection
      error, velocity while reducing the path length and increasing smoothness with a
      force of higher magnitude showing the stabilizing characteristics of higher
      magnitude forces. This approach paves a way to assess and model procedural skills
      decay. 

PMID- 27046594
TI  - Asymmetry in Dominant / Non-Dominant Hand Performance Differentiates Novices from
      Experts on an Arthroscopy Virtual Reality Serious Game.
AB  - Safe and effective arthroscopic surgery requires ambidextrous motor skills. The
      current study examined dominant versus non-dominant hand performance on a virtual
      reality serious game in a group of expert arthroscopic surgeons (n=15) compared
      to a group of orthopedic surgery residents (n=10). A virtual reality Tetris game
      was performed with the arthroscopic camera and arthroscope in one hand, using an
      arthroscopic grasping tool in the opposite hand to manipulate the virtual Tetris
      blocks onto the game grid. A second run was performed after swapping instruments
      between hands. The order of hand testing was randomized. There was no
      statistically significant difference in exercise time, grasper path length, or
      camera path length between the right and left hands of the expert surgeons. In
      contrast, there were statistically significant differences in all of these
      parameters between the two hands for the orthopedic surgery residents, with
      better performance when the grasping tool was used in the dominant hand. The
      findings of this study suggest that virtual reality games which incorporate
      progressive cognitive loading could be used to facilitate training, automation,
      and objective assessment of surgical motor skills. 

PMID- 27046595
TI  - The Virtual Pediatric Airways Workbench.
AB  - The Virtual Pediatric Airways Workbench (VPAW) is a patient-centered surgical
      planning software system targeted to pediatric patients with airway obstruction.
      VPAW provides an intuitive surgical planning interface for clinicians and
      supports quantitative analysis regarding prospective surgeries to aid clinicians
      deciding on potential surgical intervention. VPAW enables a full surgical
      planning pipeline, including importing DICOM images, segmenting the airway,
      interactive 3D editing of airway geometries to express potential surgical
      treatment planning options, and creating input files for offline geometric
      analysis and computational fluid dynamics simulations for evaluation of surgical
      outcomes. In this paper, we describe the VPAW system and its use in one case
      study with a clinician to successfully describe an intended surgery outcome. 

PMID- 27046596
TI  - A Toroidal Probe for Measuring Surgically Exposed Joint Centers.
AB  - Maintaining the hip center can improve the success of a total hip arthroplasty. A
      novel probe design, based on mating a toroid with a sphere, was used for
      kinematic measurements of the femoral head center and implant center in a pre
      clinical study of hip joints. In an electromagnetically tracked implementation
      tested in a laboratory environment, the device measured a spherical center to
      within 1.2+/-0.2 mm in a technical validation. Applied to a plastic model of a
      cadaveric femur, the center of the femoral head was measured to 1.8+/-0.4 mm and
      the implant was measured to within 1.5+/-0.5 mm. Because leg length changes and
      offset changes in conventional hip arthroplasty can be as much as 16 mm, this
      device has relatively high accuracy that may improve implant localization for the
      hip. 

PMID- 27046597
TI  - Positive and Transformative Technologies for Active Ageing.
AB  - Due to advances in treatment and people's living longer, chronic diseases are
      becoming more common among our population. This is a leading contributor to the
      increasing burden on our current healthcare system. To reduce this burden and
      sufficiently meet the needs of this growing segment of the population, healthcare
      organizations must encourage the elderly to take a more active role in caring for
      their own health and well-being. Technology may offer a solution to this
      shortcoming. "Positive Technology" focuses on the use of technology for improving
      the quality of our personal experience, and it suggests specific strategies for
      modifying/improving each of the different dimensions involved - Emotional Quality
      (affect regulation); Engagement/Actualization (presence and flow); Connectdness
      (collective intentions and networked flow) - and for generating motivation and
      engagement in the process. "Transformative Technology" are technologically
      mediated experiences that support positive, enduring transformation of the self
      world. The transformative content is delivered through a set of experiential
      affordances, which are stimuli designed to elicit emotional and cognitive
      involvement in the designed experience: (i) emotional affordances; (ii) epistemic
      affordances. The paper discusses discuss the possible role of positive and
      transormative technologies for healthy living and active ageing by presenting
      different practical applications of this approach recently developed by our team.

PMID- 27046598
TI  - Automatic Behavior Analysis During a Clinical Interview with a Virtual Human.
AB  - SimSensei is a Virtual Human (VH) interviewing platform that uses off-the-shelf
      sensors (i.e., webcams, Microsoft Kinect and a microphone) to capture and
      interpret real-time audiovisual behavioral signals from users interacting with
      the VH system. The system was specifically designed for clinical interviewing and
      health care support by providing a face-to-face interaction between a user and a
      VH that can automatically react to the inferred state of the user through
      analysis of behavioral signals gleaned from the user's facial expressions, body
      gestures and vocal parameters. Akin to how non-verbal behavioral signals have an
      impact on human-to-human interaction and communication, SimSensei aims to capture
      and infer user state from signals generated from user non-verbal communication to
      improve engagement between a VH and a user and to quantify user state from the
      data captured across a 20 minute interview. Results from of sample of service
      members (SMs) who were interviewed before and after a deployment to Afghanistan
      indicate that SMs reveal more PTSD symptoms to the VH than they report on the
      Post Deployment Health Assessment. Pre/Post deployment facial expression analysis
      indicated more sad expressions and few happy expressions at post deployment. 

PMID- 27046599
TI  - Improving the Acquisition of Basic Technical Surgical Skills with VR-Based
      Simulation Coupled with Computer-Based Video Instruction.
AB  - Next to practice, feedback is the most important variable in skill acquisition.
      Feedback can vary in content and the way that it is used for delivery. Health
      professions education research has extensively examined the different effects
      provided by the different feedback methodologies. In this paper we compared two
      different types of knowledge of performance (KP) feedback. The first type was
      video-based KP feedback while the second type consisted of computer generated KP
      feedback. Results of this study showed that computer generated performance
      feedback is more effective than video based performance feedback. The combination
      of the two feedback methodologies provides trainees with a better understanding. 

PMID- 27046600
TI  - The Role of Game Elements in Online Learning within Health Professions Education.
AB  - Given the highly competitive and motivating nature of today's students,
      gamification, when properly implemented, can be an effective learning tool. Here
      we studied which gamification (gaming) elements that medical students would be
      interested in having when using an online learning system to acquire clinical
      skills. Focus groups sessions were held with medical students, game developers,
      and game designers to develop an understanding about their perception and
      preferences regarding gamification. Overall it was determined that gamification
      will lead to increased engagement and motivation and should include both
      competitive and social elements. 

PMID- 27046601
TI  - Real Time Gabor-Domain Optical Coherence Microscopy for 3D Imaging.
AB  - Fast, robust, nondestructive 3D imaging is needed for the characterization of
      microscopic tissue structures across various clinical applications. A custom
      microelectromechanical system (MEMS)-based 2D scanner was developed to achieve,
      together with a multi-level GPU architecture, 55 kHz fast-axis A-scan acquisition
      in a Gabor-domain optical coherence microscopy (GD-OCM) custom instrument. GD-OCM
      yields high-definition micrometer-class volumetric images. A dynamic depth of
      focusing capability through a bio-inspired liquid lens-based microscope design,
      as in whales' eyes, was developed to enable the high definition instrument
      throughout a large field of view of 1 mm3 volume of imaging. Developing this
      technology is prime to enable integration within the workflow of clinical
      environments. Imaging at an invariant resolution of 2 MUm has been achieved
      throughout a volume of 1 * 1 * 0.6 mm3, acquired in less than 2 minutes.
      Volumetric scans of human skin in vivo and an excised human cornea are presented.

PMID- 27046602
TI  - The Communication of Global Cardiovascular Risk by Avatars.
AB  - Communicating numerical estimates of cardiovascular risk (CVR) to patients
      encourage risk reduction actions. Avatars may enhance the risk messages ability
      to improve persuasion to adhere to healthy behaviors. We compared the efficacy of
      a computer-based aid communicating CVR with and without animated avatars for
      improving intention to adhere to lifestyle changes. Males with intermediate to
      high CVR received their risk message in 2 versions: an avatar using voice; voice
      only. Forty-one participants completed the study. Intent to change lifestyle
      showed a significant effect favoring the avatar (moderate effect size). Intent to
      follow medical treatments also showed a significant effect favoring the avatar
      (moderate effect size). An avatar-based computer aid significantly increased
      participants' intention to adhere to positive behavioral changes. 

PMID- 27046603
TI  - GPU-Based Parallelized Solver for Large Scale Vascular Blood Flow Modeling and
      Simulations.
AB  - Cardio-vascular blood flow simulations are essential in understanding the blood
      flow behavior during normal and disease conditions. To date, such blood flow
      simulations have only been done at a macro scale level due to computational
      limitations. In this paper, we present a GPU based large scale solver that
      enables modeling the flow even in the smallest arteries. A mechanical equivalent
      of the circuit based flow modeling system is first developed to employ the GPU
      computing framework. Numerical studies were employed using a set of 10 million
      connected vascular elements. Run-time flow analysis were performed to simulate
      vascular blockages, as well as arterial cut-off. Our results showed that we can
      achieve ~100 FPS using a GTX 680m and ~40 FPS using a Tegra K1 computing
      platform. 

PMID- 27046604
TI  - Multi-Kinect v2 Camera Based Monitoring System for Radiotherapy Patient Safety.
AB  - 3D kinect camera systems are essential for real-time imaging of 3D treatment
      space that consists of both the patient anatomy as well as the treatment
      equipment setup. In this paper, we present the technical details of a 3D
      treatment room monitoring system that employs a scalable number of calibrated and
      coregistered Kinect v2 cameras. The monitoring system tracks radiation gantry and
      treatment couch positions, and tracks the patient and immobilization accessories.
      The number and positions of the cameras were selected to avoid line-of-sight
      issues and to adequately cover the treatment setup. The cameras were calibrated
      with a calibration error of 0.1 mm. Our tracking system evaluation show that both
      gantry and patient motion could be acquired at a rate of 30 frames per second.
      The transformations between the cameras yielded a 3D treatment space accuracy of
      < 2 mm error in a radiotherapy setup within 500mm around the isocenter. 

PMID- 27046605
TI  - A New Design for Airway Management Training with Mixed Reality and High Fidelity
      Modeling.
AB  - Restoring airway function is a vital task in many medical scenarios. Although
      various simulation tools have been available for learning such skills, recent
      research indicated that fidelity in simulating airway management deserves further
      improvements. In this study, we designed and implemented a new prototype for
      practicing relevant tasks including laryngoscopy, intubation and cricothyrotomy.
      A large amount of anatomical details or landmarks were meticulously selected and
      reconstructed from medical scans, and 3D-printed or molded to the airway
      intervention model. This training model was augmented by virtually and physically
      presented interactive modules, which are interoperable with motion tracking and
      sensor data feedback. Implementation results showed that this design is a
      feasible approach to develop higher fidelity airway models that can be integrated
      with mixed reality interfaces. 

PMID- 27046606
TI  - A Motion Tracking and Sensor Fusion Module for Medical Simulation.
AB  - Here we introduce a motion tracking or navigation module for medical simulation
      systems. Our main contribution is a sensor fusion method for proximity or
      distance sensors integrated with inertial measurement unit (IMU). Since IMU
      rotation tracking has been widely studied, we focus on the position or trajectory
      tracking of the instrument moving freely within a given boundary. In our
      experiments, we have found that this module reliably tracks instrument motion. 

PMID- 27046607
TI  - Constrained Point-Based Framework with Efficient Mechanical Interaction for
      Virtual Surgery.
AB  - This paper proposes a stable and volume conserving meshless approach for soft
      tissue deformation in virtual surgery, where an efficient tissue-tissue
      interaction scheme is designed for interacting deformable bodies. Specifically,
      we integrate position-based volume constraint into point-based framework in order
      to conserve the total volume of deformable bodies and maintain the stability of
      the simulation. Moreover, we resolve the tissue-tissue interactions of deformable
      bodies with position-based contact model, which directly computes the
      displacement caused by normal and shear stress. The proposed approach can be
      regarded as a fast approximation of the precise contact model. Experimental
      results demonstrate that our approach can well enforce the volume conservation of
      deformable bodies, and obtain visual plausible behaviors for multiple organs
      interactions. 

PMID- 27046608
TI  - A Novel Platform for Assessment of Surgical Suturing Skill: Preliminary Results.
AB  - In this work, we describe a novel platform for quantifying surgical suturing
      skill. Forces and user movements are recorded using sensors during suturing
      maneuvers performed on a suture patch. Preliminary results from a pilot
      experiment suggest that force data could be used for objective assessment of
      suturing skill. 

PMID- 27046609
TI  - A Capacitance-Based Sensor for Hemodialysis Cannulation Training: A Proof-of
      Concept Study.
AB  - In this work, we present a novel capacitance-based sensor for teaching
      hemodialysis cannulation skills. Initial results from a pilot experiment suggest
      that data from the sensor could be used to indicate puncture events in tissue
      like materials. 

PMID- 27046610
TI  - Automated Detection of Heterogeneity in Medical Tactile Images.
AB  - Artificial tactile sensing is a capability important for many applications and,
      in particular, for endoscopic surgery. A recently developed Medical Tactile
      Endosurgical Complex (MTEC) that is a certified and commercially available
      product is an efficient tool that provides such a capability. Currently the
      analysis of intraoperative tactile images that are registered and visualized by
      MTEC is performed manually by a surgeon. We show that heterogeneity detection - a
      key constituent of intraoperative tactile images analysis - can be efficiently
      automated. Such automation essentially reduces the requirement of attention
      retaining during the MTEC-based palpation. 

PMID- 27046611
TI  - Reduced Imaging Rate in Liver Elastometery Using Shear Wave Interference
      Patterns.
AB  - Inducing interference patterns of shear wave is one of the proposed methods for
      reducing the frame rate in measuring wave speed during tissue elastography.
      Previously, the Nyquist rate must be met in order to provide an appropriate image
      for extracting the patterns with a reasonable accuracy. In this article we
      propose a technique based on image registration, and apply it to ultrasound
      images acquired before and after inducing the shear waves to estimate the
      amplitude of displacement. The displacement of the tissue is then used to form
      the interference pattern of shear waves. The method does not induce any
      restrictions on the time interval between images, so the tissue elasticity can be
      calculated independent of the imaging rate. The average error in measuring the
      elasticity of the simulated phantom is 13.7%. 

PMID- 27046612
TI  - Development of Four Dimensional Human Model that Enables Deformation of Skin,
      Organs and Blood Vessel System During Body Movement - Visualizing Movements of
      the Musculoskeletal System.
AB  - We constructed a four dimensional human model that is able to visualize the
      structure of a whole human body, including the inner structures, in real-time to
      allow us to analyze human dynamic changes in the temporal, spatial and
      quantitative domains. To verify whether our model was generating changes
      according to real human body dynamics, we measured a participant's skin expansion
      and compared it to that of the model conducted under the same body movement. We
      also made a contribution to the field of orthopedics, as we were able to devise a
      display method that enables the observer to more easily observe the changes made
      in the complex skeletal muscle system during body movements, which in the past
      were difficult to visualize. 

PMID- 27046613
TI  - Evaluation of Network-Based Minimally Invasive VR Surgery Simulator.
AB  - In this paper, we report a result of an experiment of a field trial of our
      network-based minimally invasive surgery simulator. In our previous paper, we
      proposed a network-based visuohaptic surgery training system for laparoscopic
      surgery. In addition, we proposed a volume-based haptic communication approach,
      which allows participants at remote sites on the network to simultaneously
      interact with the same target object in virtual environments presented by multi
      level computer performance systems, by only exchanging a small set of
      manipulation parameters for the target object and additional packet for
      synchronization of status of binary tree and deformation of shared volume model.
      We implemented the approach into our network-based surgery simulator, and field
      trial of the simulator at three locations was performed. 

PMID- 27046614
TI  - Natural Language Understanding Performance & Use Considerations in Virtual
      Medical Encounters.
AB  - A virtual standardized patient (VSP) prototype was tested for natural language
      understanding (NLU) performance. The conversational VSP was evaluated in a
      controlled 61 subject study over four repetitions of a patient case. The
      prototype achieved more than 92% appropriate response rate from naive users on
      their first attempt and results were stable by their fourth case repetition. This
      level of performance exceeds prior efforts and is at a level comparable of
      accuracy as seen in human conversational patient training, with caveats. This
      level of performance was possible due to the use of a unified medical taxonomy
      underpinning that allows virtual patient language training to be applied to all
      cases in our system as opposed to benefiting a single patient case. 

PMID- 27046615
TI  - Quantified-Self for Obesity: Physical Activity Behaviour Sensing to Improve
      Health Outcomes.
AB  - Physical activity levels in bariatric patients have not been well documented,
      despite their importance in maintaining weight loss following surgery. This study
      investigated the feasibility of tracking physical activity using a smartphone app
      with minimal user interaction. Thus far, we have obtained good quality data from
      255 patients at various points in their weight loss journey. Preliminary analyses
      indicate little change in physical activity levels following surgery with pre
      surgery patients reaching an average of 16 minutes per day and post-surgery
      patients achieving a daily average of 21 minutes. Further analyses using machine
      learning techniques will be conducted to determine whether physical activity is a
      critical factor in distinguishing between successful and unsuccessful weight loss
      outcomes and in the resolution of comorbid conditions in patients with similar
      clinical profiles. 

PMID- 27046616
TI  - Using Motion-Sensor Games to Encourage Physical Activity for Adults with
      Intellectual Disability.
AB  - Adults with Intellectual Disability (ID) are at high risk of being in poor health
      as a result of exercising infrequently; recent evidence indicates this is often
      due to there being a lack of opportunities to exercise. This pilot study involved
      an investigation of the use of motion-sensor game technology to enable and
      encourage exercise for this population. Five adults (two female; 3 male, aged 34
      74 [M = 55.20, SD = 16.71] with ID used motion-sensor games to conduct exercise
      at weekly sessions at a day-centre. Session attendees reported to have enjoyed
      using the games, and that they would like to use the games in future. Interviews
      were conducted with six (four female; two male, aged 27-51 [M = 40.20, SD =
      11.28]) day-centre staff, which indicated ways in which the motion-sensor games
      could be improved for use by adults with ID, and barriers to consider in relation
      to their possible future implementation. Findings indicate motion-sensor games
      provide a useful, enjoyable and accessible way for adults with ID to exercise.
      Future research could investigate implementation of motion-sensor games as a
      method for exercise promotion for this population on a larger scale. 

PMID- 27046617
TI  - Usability Comparisons of Head-Mounted vs. Stereoscopic Desktop Displays in a
      Virtual Reality Environment with Pain Patients.
AB  - Researchers have shown that immersive Virtual Reality (VR) can serve as an
      unusually powerful pain control technique. However, research assessing the
      reported symptoms and negative effects of VR systems indicate that it is
      important to ascertain if these symptoms arise from the use of particular VR
      display devices, particularly for users who are deemed "at risk," such as chronic
      pain patients Moreover, these patients have specific and often complex needs and
      requirements, and because basic issues such as 'comfort' may trigger anxiety or
      panic attacks, it is important to examine basic questions of the feasibility of
      using VR displays. Therefore, this repeated-measured experiment was conducted
      with two VR displays: the Oculus Rift's head-mounted display (HMD) and Firsthand
      Technologies' immersive desktop display, DeepStream3D. The characteristics of
      these immersive desktop displays differ: one is worn, enabling patients to move
      their heads, while the other is peered into, allowing less head movement. To
      assess the severity of physical discomforts, 20 chronic pain patients tried both
      displays while watching a VR pain management demo in clinical settings. Results
      indicated that participants experienced higher levels of Simulator Sickness using
      the Oculus Rift HMD. However, results also indicated other preferences of the two
      VR displays among patients, including physical comfort levels and a sense of
      immersion. Few studies have been conducted that compare usability of specific VR
      devices specifically with chronic pain patients using a therapeutic virtual
      environment in pain clinics. Thus, the results may help clinicians and
      researchers to choose the most appropriate VR displays for chronic pain patients
      and guide VR designers to enhance the usability of VR displays for long-term pain
      management interventions. 

PMID- 27046618
TI  - 3D Physics-Based Registration of 2D Dynamic MRI Data.
AB  - We present a method allowing for intra-operative targeting of a specific
      anatomical feature. The method is based on a registration of 3D pre-operative
      data to 2D intra-operative images. Such registration is performed using an
      elastic model reconstructed from the 3D images, in combination with sliding
      constraints imposed via Lagrange multipliers. We register the pre-operative data,
      where the feature is clearly detectable, to intra-operative dynamic images where
      such feature is no more visible. Despite the lack of visibility on the 2D MRI
      images, we are able both to determine the location of the target as well as
      follow its displacement due to respiratory motion. 

PMID- 27046619
TI  - Importance of Stereoscopy in Haptic Training of Novice Temporal Bone Surgery.
AB  - We investigate the effects of stereoscopic simulation on novice trainee surgical
      performance. METHODS: 20 first year medical students were randomized into a
      stereo or non-stereo group. Each participant viewed a 13 minute instructional
      video and then performed 3 mastoidectomy procedures with an in-house haptic
      temporal bone simulation, using a 3D-capable display with either active (stereo)
      or inactive (non-stero) shutter glasses. Following training, participants
      performed an actual mastoidectomy on a single 3D-printed bone model. The printed
      models were evaluated by 3 blinded neurotologic surgeons using a 7 point grading
      system. RESULTS: Two-tailed t-tests showed no significant difference in overall
      performance (mean score across test categories over all subjects) between stereo
      (M=3.8, SD=1.1) and non-stereo (M=4.4, SD=1.5) conditions (p=0.163). No
      significant differences existed in any of the assessed sub-domains. CONCLUSIONS:
      The addition of stereo-vision to haptic training may not affect temporal bone
      surgical skill acquisition in novice users.

PMID- 27046620
TI  - Gunner Goggles: Implementing Augmented Reality into Medical Education.
AB  - There is evidence that both smartphone and tablet integration into medical
      education has been lacking. At the same time, there is a niche for augmented
      reality (AR) to improve this process through the enhancement of textbook
      learning. Gunner Goggles is an attempt to enhance textbook learning in shelf exam
      preparatory review with augmented reality. Here we describe our initial prototype
      and detail the process by which augmented reality was implemented into our
      textbook through Layar. We describe the unique functionalities of our textbook
      pages upon augmented reality implementation, which includes links, videos and 3D
      figures, and surveyed 24 third year medical students for their impression of the
      technology. Upon demonstrating an initial prototype textbook chapter, 100%
      (24/24) of students felt that augmented reality improved the quality of our
      textbook chapter as a learning tool. Of these students, 92% (22/24) agreed that
      their shelf exam review was inadequate and 19/24 (79%) felt that a completed
      Gunner Goggles product would have been a viable alternative to their shelf exam
      review. Thus, while students report interest in the integration of AR into
      medical education test prep, future investigation into how the use of AR can
      improve performance on exams is warranted. 

PMID- 27046621
TI  - Investigating the Influence of Hand Dominance on Postural Sway During Traditional
      and Simulated Laparoscopic Surgical Skills Practice.
AB  - This study examined how hand dominance could influence postural sway during
      laparoscopic skills practice. Ten inexperienced medical trainees performed a peg
      transfer task using the Fundamentals of Laparoscopic Surgery (FLS) training box
      and the virtual reality (VR) trainer. Surface electromyographic recordings of
      upper and lower limb muscles were taken, while the postural sway was measured by
      a pressure mapping system. Skills performance using the non-dominant hand
      required more muscle effort and increased more postural sway. Compared with the
      FLS training box, training with VR decreased the use of muscle effort and could
      reduce the influence of hand dominance on the overall postural sway during
      laparoscopic surgical skills practice. 

PMID- 27046622
TI  - Physician Burnout: Improving Treatment Efficacy with Virtual Reality.
AB  - Creating a significant negative impact on both their quality of life and the
      quality of patient care with an evident economical burden for the healthcare
      system, there is a growing concern over physician burnout. The range of
      interventions and treatments that have been used to address this problem,
      however, appear quite fragmented and lack compelling efficacy. We describe the
      main factors known to contribute to the development of physician burnout as well
      as currently available treatments. Studies seem to indicate that both
      specialisation area as well as personality traits may contribute to the
      manifestation. The highest risk specialties appear to be critical care
      physicians, emergency physicians, oncologists and internal medicine physicians,
      while the highest risk personality attributes are high neuroticism, low
      agreeableness, introversion, and negative affectivity. In addition, being
      exceedingly enthusiastic about one's work and having high aspirations at work,
      with an idealistic approach, also serve as factors which contribute to increased
      risk of burnout, and in particular for those who are new to the occupation. 

PMID- 27046623
TI  - Virtual Intraoperative Cholangiogram Using WebCL.
AB  - In this paper, we propose a Virtual Intraoperative Cholangiogram (VIC) training
      platform. Intraoperative Cholangiogram (IC) is an imaging technique of biliary
      anatomy with using fluorescent fluids sensitive to the X-Rays. The procedure is
      often employed to diagnose the difficult cases such as abnormal anatomy or
      choledocholithiasis during the laparoscopic cholecystectomy. The major challenge
      in cholangiogram is accurate interpretation of the X-Ray image, which requires
      extensive case training. However, the training platforms that support generation
      of various IC cases have been lacking. In this study, we developed a web based
      platform to generate IC images from any virtual bile duct anatomy. As the
      generation of X-Ray image from 3D scene is a computationally intensive task, we
      utilized WebCL technology to parallelize the computation for achieving real-time
      rates. In this work, we present details of our WebCL IC generation algorithm and
      benchmark results. 

PMID- 27046624
TI  - Evaluation of User Performance in Simulation-Based Diagnostic Cerebral
      Angiography Training.
AB  - Simulation of anatomically complex procedures, such as angiography, is becoming
      more practical, however, computer-based modules require extensive research to
      assess their effectiveness. We organized two training schemas - alternating cases
      and consistent cases - and hypothesized that the alternating practice cases would
      be beneficial to test performance. Eight residents (4 radiology/4 neurosurgery)
      and 8 anatomy graduate students were trained on the SimbionixTM simulator in
      order to assess skill acquisition in diagnostic cerebral angiography over 8
      sessions. We found that participants improve on total procedure time and total
      fluoroscopy time (p<0.05), but not on contrast injected or roadmaps created.
      There were no significant differences between alternating and consistent training
      types. Additional work needs to be done with higher sample numbers and
      visuospatial scores as criteria.

PMID- 27046628
TI  - Getting insight into the prevalence of antibiotic resistance genes in specimens
      of marketed edible insects.
AB  - This study was aimed at investigating the occurrence of 11 transferable
      antibiotic resistance (AR) genes [erm(A), erm(B), erm(C), vanA, vanB, tet(M),
      tet(O), tet(S), tet(K), mecA, blaZ] in 11 species of marketed edible insects
      (small crickets powder, small crickets, locusts, mealworm larvae, giant
      waterbugs, black ants, winged termite alates, rhino beetles, mole crickets,
      silkworm pupae, and black scorpions) in order to provide a first baseline for
      risk assessment. Among the AR genes under study, tet(K) occurred with the highest
      frequency, followed by erm(B), tet(S) and blaZ. A high variability was seen among
      the samples, in terms of occurrence of different AR determinants. Cluster
      Analysis and Principal Coordinates Analysis allowed the 11 samples to be grouped
      in two main clusters, one including all but one samples produced in Thailand and
      the other including those produced in the Netherlands. 

PMID- 27046629
TI  - Characterization of thermophilic fungal community associated with pile
      fermentation of Pu-erh tea.
AB  - This study aimed to characterize the thermophilic fungi in pile-fermentation
      process of Pu-erh tea. Physicochemical analyses showed that the high temperature
      and low pH provided optimal conditions for propagation of fungi. A number of
      fungi, including Blastobotrys adeninivorans, Thermomyces lanuginosus, Rasamsonia
      emersonii, Aspergillus fumigatus, Rhizomucor pusillus, Rasamsonia
      byssochlamydoides, Rasamsonia cylindrospora, Aspergillus tubingensis, Aspergillus
      niger, Candida tropicalis and Fusarium graminearum were isolated as thermophilic
      fungi under combination of high temperature and acid culture conditions from Pu
      erh tea pile-fermentation. The fungal communities were analyzed by PCR-DGGE.
      Results revealed that those fungi are closely related to Debaryomyces hansenii,
      Cladosporium cladosporioides, A. tubingensis, R. emersonii, R. pusillus, A.
      fumigatus and A. niger, and the last four presented as dominant species in the
      pile process. These four preponderant thermophilic fungi reached the order of
      magnitude of 10(7), 10(7), 10(7) and 10(6)copies/g dry tea, respectively,
      measured by real-time quantitative PCR (q-PCR). The results indicate that the
      thermophilic fungi play an important role in Pu-erh tea pile fermentation. 

PMID- 27046630
TI  - Descriptive and Psychometric Properties of the Inventory of Motivations for
      Suicide Attempts (IMSA) in an Inpatient Adolescent Sample.
AB  - Little is known about why adolescents attempt suicide. The current study examined
      the endorsement, structure, and clinical correlates of adolescents' suicide
      attempt motivations as measured by the Inventory of Motivations for Suicide
      Attempts (IMSA). Suicidal adolescents (n = 52) in a psychiatric unit were
      administered the IMSA and interviewed about their suicide attempts. Psychache,
      Hopelessness, and Escape were the most strongly endorsed motivations, and
      Interpersonal Influence the least endorsed. IMSA scales exhibited a 2-factor
      solution: 1) Internal and 2) Communication. Suicide intent was strongly
      correlated with Internal motivations and moderately inversely correlated with
      Communication motivations. Factor structure and mean endorsements were similar to
      adult samples. The IMSA is a useful measure to assess attempt motivations in
      adolescents.

PMID- 27046631
TI  - CACN-1 is required in the Caenorhabditis elegans somatic gonad for proper oocyte
      development.
AB  - CACN-1/Cactin is a conserved protein identified in a genome-wide screen for genes
      that regulate distal tip cell migration in the nematode Caenorhabditis elegans.
      In addition to possessing distal tip cells that migrate past their correct
      stopping point, animals depleted of cacn-1 are sterile. In this study, we show
      that CACN-1 is needed in the soma for proper germ line development and
      maturation. When CACN-1 is depleted, sheath cells are absent and/or abnormal.
      When sheath cells are absent, hermaphrodites produce sperm, but do not switch
      appropriately to oocyte production. When sheath cells are abnormal, some oocytes
      develop but are not successfully ovulated and undergo endomitotic reduplication
      (Emo). Our previous proteomic studies show that CACN-1 interacts with a network
      of splicing factors. Here, these interactors were screened using RNAi. Depletion
      of many of these factors led to missing or abnormal sheath cells and germ line
      defects, particularly absent and/or Emo oocytes. These results suggest CACN-1 is
      part of a protein network that influences somatic gonad development and function
      through alternative splicing or post-transcriptional gene regulation.

PMID- 27046632
TI  - TTG2 controls the developmental regulation of seed coat tannins in Arabidopsis by
      regulating vacuolar transport steps in the proanthocyanidin pathway.
AB  - The brown color of Arabidopsis seeds is caused by the deposition of
      proanthocyanidins (PAs or condensed tannins) in their inner testa layer. A
      transcription factor complex consisting of TT2, TT8 and TTG1 controls expression
      of PA biosynthetic genes, just as similar TTG1-dependent complexes have been
      shown to control flavonoid pigment pathway gene expression in general. However,
      PA synthesis is controlled by at least one other gene. TTG2 mutants lack the
      pigmentation found in wild-type seeds, but produce other flavonoid compounds,
      such as anthocyanins in the shoot, suggesting that TTG2 regulates genes in the PA
      biosynthetic branch of the flavonoid pathway. We analyzed the expression of PA
      biosynthetic genes within the developing seeds of ttg2-1 and wild-type plants for
      potential TTG2 regulatory targets. We found that expression of TT12, encoding a
      MATE type transporter, is dependent on TTG2 and that TTG2 can bind to the
      upstream regulatory region of TT12 suggesting that TTG2 directly regulates TT12.
      Ectopic expression of TT12 in ttg2-1 plants partially restores seed coat
      pigmentation. Moreover, we show that TTG2 regulation of TT12 is dependent on TTG1
      and that TTG1 and TTG2 physically interact. The observation that TTG1 interacts
      with TTG2, a WRKY type transcription factor, proposes the existence of a novel
      TTG1-containing complex, and an addendum to the existing paradigm of flavonoid
      pathway regulation.

PMID- 27046633
TI  - Trapeziectomy or revision into a cemented polyethylene cup in failed
      trapeziometacarpal total joint arthroplasty.
AB  - OBJECTIVES: Total joint replacement as treatment of osteoarthritis of the
      trapeziometacarpal joint may lead to excellent short-term results, but also with
      a high risk of failure of the trapezium component. The aim of this study was to
      compare revision using trapeziectomy with a revision into a cemented trapezium
      cup. METHODS: Thirty-four patients with a mean follow-up time of 47 months were
      included in a case control study with 17 hands revised with a cemented cup and 21
      trapeziectomy. RESULTS: At follow-up, no significant difference was found in self
      reported outcome, with pain at rest or activity and in grip strength comparing
      patients revised using trapeziectomy with patients revised with insertion of a
      new cup. There was, however, a high risk of re-revision in patients treated with
      insertion of a new cup and at the follow-up 4/17 cups had been re-revised and
      5/17 cups had radiological signs of implant loosening. CONCLUSION: IT was found
      that trapeziectomy should be the standard salvage procedure after a failed
      trapezium implant and revision of cup loosening with a cemented cup has an
      unacceptable failure rate.

PMID- 27046634
TI  - Atlantoaxial Fusion: Sixteen Years of Epidemiology, Indications, and
      Complications in New York State.
AB  - STUDY DESIGN: A retrospective state database analysis. OBJECTIVE: The aim of this
      study was to describe the epidemiology and complications of as well as
      indications for primary isolated atlantoaxial fusion. SUMMARY OF BACKGROUND DATA:
      Atlantoaxial fusion involves unique indications, techniques, and complications.
      There is limited epidemiologic literature focused specifically on this procedure.
      METHODS: New York's Statewide Planning and Research Cooperative System database,
      an all-payer hospitalization reporting system, was queried to identify all
      patients undergoing primary isolated atlantoaxial fusion in the state from 1997
      to 2012. Demographic and clinical data were extracted and analyzed. United States
      Census Bureau figures were used to calculate population-adjusted surgical rates.
      RESULTS: One thousand five hundred fifty-nine patients underwent isolated primary
      atlantoaxial fusion during the study period. The overall population-adjusted
      annual surgical rate did not change significantly over time. By 2012, individuals
      aged >=70 years had the highest incidence of surgery [2.37 per 100,000
      population; 95% confidence interval (95% CI) 1.68-3.07]. Medicare was the most
      common payer (44.0% of claims). Approximately 85% of patients had a Charlson/Deyo
      Comorbidity Index of zero or one. Over time, a significantly lower proportion of
      atlantoaxial fusions were attributable to rheumatic disease, and a significantly
      higher proportion were due to fracture. By 2012, management of fractures was the
      most common indication for C1-C2 fusion (44.1% of cases). Dysphagia or dysphonia
      occurred after 0.8% of cases, dural tear after 0.3%, infection after 0.5%, and
      seroma, hematoma, or hemorrhage after 0.5%. In-hospital mortality was 2.7%, of
      which 76% had fracture as the surgical indication. CONCLUSION: Isolated
      atlantoaxial fusions have been performed at a stable, low level over the past 16
      years in New York. Although most of these patients are relatively healthy pre
      operatively, approximately one in 10 experience an in-hospital complication and
      nearly 3% die in-hospital. Knowledge of these risks will hopefully spur further
      efforts to minimize them and allow for more accurate counseling of patients and
      their families. LEVEL OF EVIDENCE: 4.

PMID- 27046635
TI  - Goal-Directed Fluid Therapy Based on Stroke Volume Variation in Patients
      Undergoing Major Spine Surgery in the Prone Position: A Cohort Study.
AB  - STUDY DESIGN: A retrospective observational study. OBJECTIVE: The aim of this
      study was to test whether a goal-directed fluid therapy (GDFT) protocol, based on
      stroke volume variation (SVV), applied in major spine surgery performed in the
      prone position, would be effective in reducing peri-operative red blood cells
      transfusions. SUMMARY OF BACKGROUND DATA: Recent literature shows that optimizing
      perioperative fluid therapy is associated with lower complication rates and
      faster recovery. METHODS: Data from 23 patients who underwent posterior spine
      arthrodesis surgery and whose intraoperative fluid administration were managed
      with the GDFT protocol were retrospectively collected and compared with data from
      23 matched controls who underwent the same surgical procedure in the same
      timeframe, and who received a liberal intraoperative fluid therapy. RESULTS:
      Patients in the GDFT group received less units of transfused red blood cells
      (primary endpoint) in the intra (0 vs. 2.0, P = 0.0 4) and postoperative period
      (2.0 vs. 4.0, P = 0.003). They also received a lower amount of intraoperative
      crystalloids, had fewer blood losses, and lower intraoperative peak lactate. In
      the postoperative period, patients in the GDFT group had fewer pulmonary
      complications and blood losses from surgical drains, needed less blood product
      transfusions, had a shorter intensive care unit stay, and a faster return of
      bowel function. We found no difference in the total length of stay among the two
      groups. CONCLUSION: Our study shows that application of a GDFT based on SVV in
      major spine surgery is feasible and can lead to reduced blood losses and
      transfusions, better postoperative respiratory performance, shorter ICU stay, and
      faster return of bowel function. LEVEL OF EVIDENCE: 3.

PMID- 27046636
TI  - Relationship Between Kyphotic Posture and Falls in Community-Dwelling Men and
      Women: The Locomotive Syndrome and Health Outcome in Aizu Cohort Study.
AB  - STUDY DESIGN: A cohort study using data from the Locomotive Syndrome and Health
      Outcome in Aizu Cohort Study, a population-based prospective cohort study of
      residents of the towns of Tadami and Minamiaizu in Fukushima Prefecture, Japan.
      OBJECTIVE: The aim of this study was to clarify the association between kyphotic
      posture and falls, and to investigate the presence or absence of sex differences.
      SUMMARY OF BACKGROUND DATA: In our literature review, we found no studies
      focusing on sex differences in the association between kyphotic posture and
      falls. METHODS: We included subjects aged more than 40 years who participated in
      annual health check-ups from 2009 to 2010. We analyzed the effects of kyphotic
      posture, measured using the wall-occiput test (WOT), on falls, adjusting for
      potential confounders, such as age, body mass index, symptoms of depression,
      sedative medication, and other comorbidities. RESULTS: We enrolled a total of
      1418 subjects into primary analyses (593 men, 825 women; mean [standard
      deviation] age, 68.1 [7.7] yrs). We then stratified subjects into the following
      groups according to the degree of kyphotic posture: nonkyphotic posture (n =
      1138, 80.3%), mild kyphotic posture (n = 172, 12.1%), and severe kyphotic posture
      (n = 108, 7.6%). We observed no significant difference in the severity of
      kyphotic posture between men and women (P = 0.18). Overall, 284 subjects (20.0%)
      experienced at least one fall during the one-year period. After adjustment for
      potential confounders using a logistic regression model, we observed a
      significant association between severe kyphotic posture and falls for men [odds
      ratio (OR) 2.14 (1.01-4.57); P = 0.048]. In contrast, we observed no significant
      association for women [OR for severe kyphotic posture 0.80 (0.43-1.50), OR for
      mild kyphotic posture 0.91 (0.53-1.57)]. CONCLUSION: We identified a sex
      difference in the association between kyphotic posture and falls in community
      dwelling adults. In particular, severe kyphotic posture might only increase the
      incidence of falls in men. LEVEL OF EVIDENCE: 3.

PMID- 27046637
TI  - The Pullout Strength of Pedicle Screws Following Redirection After Lateral Wall
      Breach or End-plate Breach.
AB  - STUDY DESIGN: Using fresh cadavers, the biomechanical testing were used to
      examine the pullout strength of each pedicle screw. OBJECTIVE: The aim of this
      study was to evaluate pullout strength of (1) a redirected pedicle screw
      following lateral wall breach; (2) a redirected pedicle screw following end-plate
      breach; and (3) a pedicle without redirection after end-plate breach without
      redirection. SUMMARY OF BACKGROUND DATA: Screw malposition, such as lateral wall
      breach or end-plate breach, is one of the main pitfalls of inserting pedicle
      screws. METHODS: From 17 fresh spines, 54 vertebrae were harvested. In each
      vertebra on one pedicle, the screw was inserted correctly down the axis of the
      pedicle, while on the other pedicle, the screw was inserted to breach the lateral
      wall or the end-plate. The 18 pedicle screws that breached the lateral wall were
      then removed and redirected along the correct axis of the pedicle. The 18 pedicle
      screws that breached the end-plate were removed and redirected along the correct
      axis of the pedicle. The 18 other pedicle screws that had breached the end-plate
      were not removed. The pullout force of pedicle screws was measured. RESULTS:
      First, the mean pullout strength for the redirected screws following lateral wall
      breach was 24.0% less as compared with the correctly aligned screws. Second, the
      mean pullout strength for the redirected screws following end-plate breach was
      23.3% less as compared with the correctly aligned screws. Third, the mean pullout
      strength for the pedicle screws end-plate breach was 7.6% less as compared with
      the correctly aligned screws. CONCLUSION: The pullout strength of redirected
      pedicle screws after either a lateral pedicle breach or end-plate breach is
      significantly less than the pullout strength of correctly aligned screw. A
      pedicle screw that is not redirected after end-plate breach is weaker than a
      pedicle screw correctly aligned; however, the difference is not significant.
      LEVEL OF EVIDENCE: N/A.

PMID- 27046639
TI  - Reliability, Validity, and Cross-Cultural Adaptation of the Turkish Version of
      the Bournemouth Questionnaire.
AB  - STUDY DESIGN: Validation of a self-report questionnaire. OBJECTIVE: The purpose
      of this study was to investigate adaptation, validity, and reliability of the
      Turkish version of the Bournemouth Questionnaire. SUMMARY OF BACKGROUND DATA: Low
      back pain is one of the most frequent disorders leading to activity limitation.
      This pain affects most of people in their lives. The most important point to
      evaluate patient's functional abilities and to decide a successful therapy
      procedure is to manage the assessment questionnaires precisely. METHODS: One
      hundred ten patients with chronic low back pain were included in present study.
      To assess reliability, test-retest and internal consistency analyses were
      applied. The results of test-retest analysis were assessed by using Intraclass
      Correlation Coefficient method (95% confidence interval). For internal
      consistency, Cronbach alpha value was calculated. Validity of the questionnaire
      was assessed in terms of construct validity. For construct validity, factor
      analysis and convergent validity were tested. For convergent validity, total
      points of the Bournemouth Questionnaire were assessed with the total points of
      Quebec Back Pain Disability Scale and Roland Morris Disability Questionnaire by
      using Pearson correlation coefficient analysis. RESULTS: Cronbach alpha value was
      found 0.914, showing that this questionnaire has high internal consistency. The
      results of test-retest analysis were varying between 0.851 and 0.927, which shows
      that test-retest results are highly correlated. Factor analysis test indicated
      that this questionnaire had one factor. Pearson correlation coefficient of the
      Bournemouth Questionnaire with Roland Morris Disability Questionnaire was
      calculated 0.703 and it was found with Quebec Back Pain Disability Scale is
      0.659. These results showed that the Bournemouth Questionnaire is very good
      correlated with Roland Morris Disability Questionnaire and Quebec Back Pain
      Disability Scale. CONCLUSION: The Turkish version of the Bournemouth
      Questionnaire is valid and reliable. LEVEL OF EVIDENCE: 3.

PMID- 27046640
TI  - High-Temperature Boc Deprotection in Flow and Its Application in Multistep
      Reaction Sequences.
AB  - A simplified Boc deprotection using a high-temperature flow reactor is described.
      The system afforded the qualitative yield of a wide variety of deprotected
      substrates within minutes using acetonitrile as the solvent and without the use
      of acidic conditions or additional workups. Highly efficient, multistep reaction
      sequences in flow are also demonstrated wherein no extraction or isolation was
      required between steps. 

PMID- 27046642
TI  - The Academy of Geriatric Physical Therapy CSM 2016 Research & Special Interest
      Platform Presentations.

PMID- 27046641
TI  - Psychometric properties of the Mini-Social Phobia Inventory (Mini-SPIN) in a
      large online treatment-seeking sample.
AB  - The Mini-Social Phobia Inventory (Mini-SPIN) is a brief, three-item measure
      designed as a screening tool for social anxiety disorder (SAD). This study
      investigated the Mini-SPIN's psychometric properties in a series of trials of
      Internet-delivered treatment. Participants were 993 people seeking Internet
      delivered cognitive behavioural therapy for a range of anxiety and mood
      disorders. Participants completed the Mini-SPIN, and were diagnosed using the
      Mini International Neuropsychiatric Interview Version 5.0.0 (MINI). They also
      completed measures of depression, general anxiety, panic, neuroticism and general
      impairment. The Mini-SPIN's ability to discriminate between people with and
      without SAD, within a large sample of people seeking treatment for a range of
      psychological disorders, was assessed at initial assessment and three-month
      follow-up. The Mini-SPIN's criterion group validity, internal consistency, test
      retest reliability, construct validity and responsiveness to treatment were also
      examined. Results demonstrated that the Mini-SPIN has an excellent ability to
      discriminate between those with and without SAD in a highly comorbid clinical
      sample, and also has good criterion group validity. The Mini-SPIN also exhibited
      excellent internal consistency, good test-retest reliability, and was responsive
      to treatment. These results highlight the Mini-SPIN's potential as an efficient
      and reliable measure of SAD in heterogeneous populations.

PMID- 27046643
TI  - Genome-wide association study of cognitive functions and educational attainment
      in UK Biobank (N=112 151).
AB  - People's differences in cognitive functions are partly heritable and are
      associated with important life outcomes. Previous genome-wide association (GWA)
      studies of cognitive functions have found evidence for polygenic effects yet, to
      date, there are few replicated genetic associations. Here we use data from the UK
      Biobank sample to investigate the genetic contributions to variation in tests of
      three cognitive functions and in educational attainment. GWA analyses were
      performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction
      time (N=111 483) and for the attainment of a college or a university degree
      (N=111 114). We report genome-wide significant single-nucleotide polymorphism
      (SNP)-based associations in 20 genomic regions, and significant gene-based
      findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and
      CADM2 genes. We report replication of these hits in published GWA studies of
      cognitive function, educational attainment and childhood intelligence. There is
      also replication, in UK Biobank, of SNP hits reported previously in GWA studies
      of educational attainment and cognitive function. GCTA-GREML analyses, using
      common SNPs (minor allele frequency>0.01), indicated significant SNP-based
      heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5%
      (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21%
      (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that
      up to 5% of the variance in cognitive test scores can be predicted in an
      independent cohort. The genomic regions identified include several novel loci,
      some of which have been associated with intracranial volume, neurodegeneration,
      Alzheimer's disease and schizophrenia.

PMID- 27046644
TI  - The role of adipokines in the rapid antidepressant effects of ketamine.
AB  - We previously found that body mass index (BMI) strongly predicted response to
      ketamine. Adipokines have a key role in metabolism (including BMI). They directly
      regulate inflammation and neuroplasticity pathways and also influence insulin
      sensitivity, bone metabolism and sympathetic outflow; all of these have been
      implicated in mood disorders. Here, we sought to examine the role of three key
      adipokines-adiponectin, resistin and leptin-as potential predictors of response
      to ketamine or as possible transducers of its therapeutic effects. Eighty
      treatment-resistant subjects who met DSM-IV criteria for either major depressive
      disorder (MDD) or bipolar disorder I/II and who were currently experiencing a
      major depressive episode received a single ketamine infusion (0.5 mg kg-1 for 40
      min). Plasma adipokine levels were measured at three time points (pre-infusion
      baseline, 230 min post infusion and day 1 post infusion). Overall improvement and
      response were assessed using percent change from baseline on the Montgomery
      Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower
      baseline levels of adiponectin significantly predicted ketamine's antidepressant
      efficacy, suggesting an adverse metabolic state. Because adiponectin
      significantly improves insulin sensitivity and has potent anti-inflammatory
      effects, this finding suggests that specific systemic abnormalities might predict
      positive response to ketamine. A ketamine-induced decrease in resistin was also
      observed; because resistin is a potent pro-inflammatory compound, this decrease
      suggests that ketamine's anti-inflammatory effects may be transduced, in part, by
      its impact on resistin. Overall, the findings suggest that adipokines may either
      predict response to ketamine or have a role in its possible therapeutic effects.

PMID- 27046645
TI  - Towards understanding and predicting suicidality in women: biomarkers and
      clinical risk assessment.
AB  - Women are under-represented in research on suicidality to date. Although women
      have a lower rate of suicide completion than men, due in part to the less-violent
      methods used, they have a higher rate of suicide attempts. Our group has
      previously identified genomic (blood gene expression biomarkers) and clinical
      information (apps) predictors for suicidality in men. We now describe pilot
      studies in women. We used a powerful within-participant discovery approach to
      identify genes that change in expression between no suicidal ideation (no SI) and
      high suicidal ideation (high SI) states (n=12 participants out of a cohort of 51
      women psychiatric participants followed longitudinally, with diagnoses of bipolar
      disorder, depression, schizoaffective disorder and schizophrenia). We then used a
      Convergent Functional Genomics (CFG) approach to prioritize the candidate
      biomarkers identified in the discovery step by using all the prior evidence in
      the field. Next, we validated for suicidal behavior the top-ranked biomarkers for
      SI, in a demographically matched cohort of women suicide completers from the
      coroner's office (n=6), by assessing which markers were stepwise changed from no
      SI to high SI to suicide completers. We then tested the 50 biomarkers that
      survived Bonferroni correction in the validation step, as well as top increased
      and decreased biomarkers from the discovery and prioritization steps, in a
      completely independent test cohort of women psychiatric disorder participants for
      prediction of SI (n=33) and in a future follow-up cohort of psychiatric disorder
      participants for prediction of psychiatric hospitalizations due to suicidality
      (n=24). Additionally, we examined how two clinical instruments in the form of
      apps, Convergent Functional Information for Suicidality (CFI-S) and Simplified
      Affective State Scale (SASS), previously tested in men, perform in women. The top
      CFI-S item distinguishing high SI from no SI states was the chronic stress of
      social isolation. We then showed how the clinical information apps combined with
      the 50 validated biomarkers into a broad predictor (UP-Suicide), our apriori
      primary end point, predicts suicidality in women. UP-Suicide had a receiver
      operating characteristic (ROC) area under the curve (AUC) of 82% for predicting
      SI and an AUC of 78% for predicting future hospitalizations for suicidality. Some
      of the individual components of the UP-Suicide showed even better results. SASS
      had an AUC of 81% for predicting SI, CFI-S had an AUC of 84% and the combination
      of the two apps had an AUC of 87%. The top biomarker from our sequential
      discovery, prioritization and validation steps, BCL2, predicted future
      hospitalizations due to suicidality with an AUC of 89%, and the panel of 50
      validated biomarkers (BioM-50) predicted future hospitalizations due to
      suicidality with an AUC of 94%. The best overall single blood biomarker for
      predictions was PIK3C3 with an AUC of 65% for SI and an AUC of 90% for future
      hospitalizations. Finally, we sought to understand the biology of the biomarkers.
      BCL2 and GSK3B, the top CFG scoring validated biomarkers, as well as PIK3C3, have
      anti-apoptotic and neurotrophic effects, are decreased in expression in
      suicidality and are known targets of the anti-suicidal mood stabilizer drug
      lithium, which increases their expression and/or activity. Circadian clock genes
      were overrepresented among the top markers. Notably, PER1, increased in
      expression in suicidality, had an AUC of 84% for predicting future
      hospitalizations, and CSNK1A1, decreased in expression, had an AUC of 96% for
      predicting future hospitalizations. Circadian clock abnormalities are related to
      mood disorder, and sleep abnormalities have been implicated in suicide.
      Docosahexaenoic acid signaling was one of the top biological pathways
      overrepresented in validated biomarkers, which is of interest given the potential
      therapeutic and prophylactic benefits of omega-3 fatty acids. Some of the top
      biomarkers from the current work in women showed co-directionality of change in
      expression with our previous work in men, whereas others had changes in opposite
      directions, underlying the issue of biological context and differences in
      suicidality between the two genders. With this study, we begin to shed much
      needed light in the area of female suicidality, identify useful objective
      predictors and help understand gender commonalities and differences. During the
      conduct of the study, one participant committed suicide. In retrospect, when the
      analyses were completed, her UP-Suicide risk prediction score was at the 100
      percentile of all participants tested.

PMID- 27046646
TI  - Genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus
      accumbens as discriminators of methamphetamine addiction and abstinence.
AB  - Epigenetic consequences of exposure to psychostimulants are substantial but the
      relationship of these changes to compulsive drug taking and abstinence is not
      clear. Here, we used a paradigm that helped to segregate rats that reduce or stop
      their methamphetamine (METH) intake (nonaddicted) from those that continue to
      take the drug compulsively (addicted) in the presence of footshocks. We used that
      model to investigate potential alterations in global DNA hydroxymethylation in
      the nucleus accumbens (NAc) because neuroplastic changes in the NAc may
      participate in the development and maintenance of drug-taking behaviors. We found
      that METH-addicted rats did indeed show differential DNA hydroxymethylation in
      comparison with both control and nonaddicted rats. Nonaddicted rats also showed
      differences from control rats. Differential DNA hydroxymethylation observed in
      addicted rats occurred mostly at intergenic sites located on long and short
      interspersed elements. Interestingly, differentially hydroxymethylated regions in
      genes encoding voltage (Kv1.1, Kv1.2, Kvb1 and Kv2.2)- and calcium (Kcnma1, Kcnn1
      and Kcnn2)-gated potassium channels observed in the NAc of nonaddicted rats were
      accompanied by increased mRNA levels of these potassium channels when compared
      with mRNA expression in METH-addicted rats. These observations indicate that
      changes in differentially hydroxymethylated regions and increased expression of
      specific potassium channels in the NAc may promote abstinence from drug-taking
      behaviors. Thus, activation of specific subclasses of voltage- and/or calcium
      gated potassium channels may provide an important approach to the beneficial
      treatment for METH addiction.

PMID- 27046647
TI  - A polymorphism in the norepinephrine transporter gene is associated with
      affective and cardiovascular disease through a microRNA mechanism.
AB  - Norepinephrine released from sympathetic nerves is removed from the neuroeffector
      junction via the action of the norepinephrine transporter (NET). NET impairment
      is evident in several clinically important conditions including major depressive
      disorder (MDD), panic disorder (PD), essential hypertension and the postural
      orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single
      nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene
      is associated with NET impairment and to elucidate the mechanisms involved. The
      analyses were carried out in two cohorts of European ancestry, which included
      healthy controls and MDD, PD, hypertensive and POTS patients. Compared with
      controls, cases had significantly higher prevalence of the T allele of rs7194256
      (C/T), arterial norepinephrine, depression and anxiety scores, larger left
      ventricular mass index, higher systolic and diastolic blood pressures, and heart
      rate. Bioinformatic analysis identified that the microRNA miR-19a-3p could bind
      preferentially to the sequence created by the presence of the T allele. This was
      supported by results of luciferase assays. Compared with controls, cases had
      significantly lower circulating miR-19a-3p, which was associated with pathways
      related to blood pressure and regulation of neurotransmission. In vitro
      norepinephrine downregulated miR-19a-3p. In conclusion, the T allele of the
      rs7194256 SNP in the 3'UTR of the NET gene is more prevalent in diseases where
      NET impairment is evident. This might be explained by the creation of a binding
      site for the microRNA miR-19a-3p. A defect in NET function may potentiate the
      sympathetic neurochemical signal, predisposing individuals with affective
      diseases to increased risk of cardiovascular disease development.

PMID- 27046648
TI  - Circadian rhythm dysfunction: a novel environmental risk factor for Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder.
      Although rare genetically linked cases of PD have been reported, most incidences
      are sporadic in nature. Late-onset, sporadic PD is thought to result from the
      combined effects of genetic and environmental risk factors exposure. Sleep and
      circadian rhythm disorders are recurrent among PD patients and appear early in
      the disease. Although some evidence supports a relationship between circadian
      disruption (CD) and PD, whether this is secondary to the motor symptoms or,
      indeed, is a factor that contributes to the pathogenesis of the disease remains
      to be investigated. In the present paper, we studied the direct consequence of
      chronic CD on the development of the phenotype in the MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridinen) model of PD. Pre-exposure to CD to mice treated with
      MPTP resulted in an exacerbation of motor deficit and a significant reduction in
      the capability of acquiring motor skills. These changes were associated with a
      greater loss of tyrosine hydroxylase cell content and intense neuroinflammation.
      Taken together, our findings demonstrate that CD by triggering a robust
      neuroinflammatory reaction and degeneration of the nigral-dopaminergic neuronal
      system exacerbates motor deficit. They support the novel hypothesis that
      circadian rhythm disorder is an environmental risk factor for developing PD.

PMID- 27046649
TI  - Epoxy Monomers Cured by High Cellulosic Nanocrystal Loading.
AB  - The present study focuses on the use of cellulose nanocrystals (CNC) as the main
      constituent of a nanocomposite material and takes advantage of hydroxyl groups,
      characteristic of the CNC chemical structure, to thermally cross-link an epoxy
      resin. An original and simple approach is proposed, based on the collective
      sticking of CNC building blocks with the help of a DGEBA/TGPAP-based epoxy resin.
      Scientific findings suggest that hydroxyl groups act as a toxic-free cross
      linking agent of the resin. The enhanced protection against water degradation as
      compared to neat CNC film and the improvement of mechanical properties of the
      synthesized films are attributed to a good compatibility between the CNC and the
      resin. Moreover, the preservation of CNC optical properties at high
      concentrations opens the way to applying these materials in photonic devices.

PMID- 27046650
TI  - Impediments to a unified international approach to the interpretation and
      management of intrapartum cardiotocographs.
AB  - There is much inconsistency in management recommendations for cardiotocograms by
      international organizations. Impediments to achieving consensus include
      disagreement on the spectrum of risk of fetal acidemia, different fetal heart
      rate pattern display due to differing chart paper speed, and the necessity for
      ancillary testing in confirming fetal acidemia.

PMID- 27046651
TI  - LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in
      colorectal cancer by inhibiting miR-204-5p.
AB  - Recent preliminary studies reported the in vitro tumor-promoting effects of long
      non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer
      (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC
      remain unclear. Therefore, we investigated the detailed role and mechanism of
      UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively
      correlated with survival time in two CRC cohorts. Functional assays revealed the
      in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can
      decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further
      mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and
      inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The
      protein levels of CREB1 were significantly up-regulated in CRCs, negatively
      associated with survival time and positively correlated with the UCA1 expression.
      The present work provides the first evidence of a UCA1-miR-204-5p
      CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are
      potential new oncogenes and prognostic factors for CRC. 

PMID- 27046652
TI  - Deconstructing 'Mabel'.

PMID- 27046653
TI  - Safety and efficacy of fesoterodine fumarate in patients with overactive bladder:
      results of a post-marketing surveillance study in Korea.
AB  - OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of
      fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive
      bladder (OAB) in routine clinical practice. METHODS: This was an open-label, non
      interventional, prospective, post-marketing surveillance study submitted to the
      Korean Ministry of Food and Drug Safety. A total of 3109 patients aged >=18 years
      with OAB symptoms were prescribed flexible doses of fesoterodine at the
      investigator's discretion. Safety was assessed based upon the reporting of
      adverse events (AEs). Efficacy was evaluated on the basis of patient self
      assessment using a bladder diary as well as on the basis of investigator
      assessment in terms of overall clinical efficacy. RESULTS: A final analysis was
      performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy
      analysis, respectively. The mean treatment duration of fesoterodine was 83.2
      days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for
      more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107),
      constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean
      episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI)
      per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the
      final follow-up visit, the investigators found improvement in clinical efficacy
      for the majority of patients (90.1%, 2684/2978). Limitations of this study
      include the observational study design and the relatively short treatment
      duration. CONCLUSION: These results suggest that fesoterodine is a well tolerated
      and effective treatment for Korean patients with OAB in routine clinical
      practice.

PMID- 27046654
TI  - Effect of a participatory organizational-level occupational health intervention
      on short-term sickness absence: a cluster randomized controlled trial.
AB  - OBJECTIVES: The aim of this study was to examine whether employees in pre-schools
      that implemented a participatory organizational-level intervention focusing on
      the core task at work had a lower incidence of short-term sickness absence
      compared to employees in the control group. METHODS: The cluster randomized
      controlled trial (RCT) comprised 78 pre-schools that were allocated to the
      intervention (44 pre-schools with 1760 employees) or control (34 pre-schools with
      1279 employees) group. The intervention lasted 25 months and followed a stepwise
      and structured approach, consisting of seminars, workshops, and workplace
      directed intervention activities focusing on the core task at work. Using Poisson
      regression, we tested differences in incidence rates in short-term sickness
      absence between the intervention and control groups during a 29-months follow-up.
      RESULTS: Estimated short-term sickness absence days per person-year during follow
      up were 8.68 and 9.17 in the intervention and control groups, respectively. The
      rate ratio (RR) for comparing incident sickness absence in the intervention to
      control groups during follow-up was 0.93 [95% confidence interval (95% CI) 0.86
      1.00] in the crude analysis and 0.89 (95% CI 0.83-0.96) when adjusting for age,
      sex, job group, type and size of workplace, and workplace average level of
      previous short-term sickness absence. A supplementary analysis showed that the
      intervention also was associated with a reduced risk of long-term sickness
      absence with a crude RR of 0.83 (95% CI 0.69-0.99) and an adjusted RR of 0.84
      (95% CI 0.69-1.01). CONCLUSIONS: Pre-school employees participating in an
      organizational-level occupational health intervention focusing on the core task
      at work had a lower incidence of short-term sickness absence during a 29-month
      follow-up compared with control group employees.

PMID- 27046655
TI  - Role of Dexmedetomidine for Sedation in Neurocritical Care Patients: A
      Qualitative Systematic Review and Meta-analysis of Current Evidence.
AB  - INTRODUCTION: This systematic review appraises the clinical evidence on efficacy
      and safety of dexmedetomidine (DEX), as a sole sedative or as sedative adjunct in
      adult neurocritical care (NCC) patients. MATERIALS AND METHODS: A database search
      was conducted to identify randomized clinical trials and observational studies
      reporting the use of DEX alone or as adjunct for sedation in NCC setting. The
      primary outcome was the occurrence of hemodynamic changes, whereas the secondary
      outcomes were sedative and analgesic efficacy, quality and time to awakening, and
      development of adverse events. RESULTS: Eight trials including 3 randomized
      controlled trials and 5 observational studies, enrolling 650 patients, were
      selected. All the retrieved studies had a high risk of bias and a low to moderate
      quality. Dexmedetomidine provided a better sedation score and reduced analgesic
      requirements when compared to propofol or midazolam sedation. No statistically
      significant difference in the combined hemodynamic effect (hypotension or
      bradycardia) between DEX and controls (risk ratio, 1.50; 95% confidence interval,
      0.65-3.48; P = 0.34; I = 56%) was identified. Adverse events were not
      consistently reported. CONCLUSIONS: Available clinical literature supporting the
      efficacy and safety of DEX use in adult NCC setting is of limited quantity and
      quality. However, from the current evidence on the use of DEX in NCC, as sole
      sedative agent or as an adjunct, seems to be both efficient and safe.

PMID- 27046656
TI  - High-Dose Naltrexone Treatment and Gender in Alcohol Dependence.
AB  - OBJECTIVES: Little is known about whether safety and effectiveness of high-dose
      naltrexone (150 mg/d) are different in alcohol-dependent women and men. This
      study investigated sex differences in safety and treatment outcomes in alcohol
      dependent women and men on high-dose naltrexone (150 mg/d). METHODS: In this
      exploratory study, safety and effectiveness of high-dose naltrexone (150 mg/d)
      were examined in men and women with alcohol dependence (n = 24; 11 men and 13
      women) treated in an 8-week outpatient setting. RESULTS: Women and men had
      similar dropout rates, adverse effects, tolerability, and hepatic function during
      high-dose naltrexone treatment (150 mg/d). Drinking outcomes were significantly
      improved in both women and men, but no sex differences were found. CONCLUSIONS:
      High-dose naltrexone seems to be well tolerated, safe, and effective in both men
      and women with alcohol dependence in this small study. Given the small sample
      size of the current study, our results cannot be considered definitive, and
      larger trials with longer durations are needed to confirm these findings.

PMID- 27046657
TI  - Indomethacin-Induced Psychotic Disorder.

PMID- 27046658
TI  - Effective Treatment of Paroxysmal Nonkinesigenic Dyskinesia With Oxcarbazepine.
AB  - Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare chronic disorder
      characterized by intermittent, non-movement-related involuntary movements. The
      response to currently available therapies is inconsistent and temporary. We
      describe here a patient with infantile-onset PNKD who failed a number of
      pharmaceutical agents used alone or in combination. Treatment with oxcarbazepine
      resulted in a substantial reduction in the frequency and severity of episodes.
      The patient has been followed for 4 years now, and the outcome of treatment is
      consistently favorable. Oxcarbazepine has been effective in managing the
      kinesigenic form of this disorder; however, its use has never been reported in
      PNKD to our knowledge. Oxcarbazepine is safer and better tolerated than most of
      the drugs currently used for treating PNKD, but blinded clinical trials are
      needed to verify its efficacy in the management of this debilitating, often
      difficult-to-treat disease. 

PMID- 27046659
TI  - Summertime Dyskinesia-Hyperpyrexia Syndrome: The "Dual Heat" Hypothesis.
AB  - The dyskinesia-hyperpyrexia syndrome is a rare complication of Parkinson disease.
      Here, we present an exceptional case affected by this syndrome. Its singularity
      is 2-fold. On one hand, the patient presented periodic episodes of dyskinesia
      hyperpyrexia during 3 consecutive summers. On the other, after unsuccessfully
      trying several therapies, she had an excellent response to an infusion of enteral
      L-dopa. Both features allow us to hypothesize that this complication is central
      in origin and propose a new potential mean of treating future refractory cases. 

PMID- 27046660
TI  - Priapism and Hypersexuality Associated With Rotigotine in an Elderly Parkinsonian
      Patient: A Case Report.

PMID- 27046661
TI  - Rescue Therapy Using Rituximab for Multiple Sclerosis.
AB  - OBJECTIVES: The aim of the study was to describe the effectiveness and safety
      data of rituximab in a group of patients with relapsing-remitting multiple
      sclerosis (MS) treated with rituximab due to failure of previous treatments or
      concomitant autoimmune diseases. METHODS: This is an observational study.
      Rituximab was considered in case of failure of the second-line therapy, failure
      of the first-line therapy and a contraindication to second-line therapies, or
      concomitant autoimmune disease. Relapses, the Expanded Disability Status Scale,
      the EQ VAS, and magnetic resonance imaging activity were assessed. RESULTS: This
      study included 12 patients with relapsing-remitting MS. The mean (range) age of
      the patients was 35 (19-54) years. Ten patients were treated with rituximab
      because of treatment failure, and 2 patients were treated with rituximab because
      of the development of idiopathic thrombocytopenic purpura. The mean (range)
      follow-up duration after beginning rituximab was 40 (18-72) months. Rituximab was
      well tolerated, because no patient experienced serious adverse reactions or
      discontinued treatment. During treatment with rituximab, no patient suffered a
      clinical relapse, and magnetic resonance imaging activity was not detected. The
      Expanded Disability Status Scale scores improved in 11 of 12 patients and
      remained stable in 1 patient. The EuroQol visual analogue scale scores improved
      in 8 of 9 patients in whom the EuroQol visual analogue scale was assessed.
      CONCLUSIONS: Treatment with rituximab seems to be safe and effective for some
      patients with relapsing-remitting MS who have failed to respond to first- and
      second-line therapies and may also be a useful option for patients with
      concomitant autoimmune disorders.

PMID- 27046662
TI  - Statin Use and Cognitive Impairment in Patients With Type 1 Diabetes: An
      Observational Study.
AB  - OBJECTIVE: We aimed to assess a wide range of cognitive functions in patients
      with type 1 diabetes (DM1) compared with healthy control subjects and to evaluate
      the effects of statins on cognitive functions in DM1 patients. MATERIALS AND
      METHODS: The sample studied consisted of 55 DM1 patients (80.0% with
      hyperlipidemia, 20% with statin treatment) and 36 age-matched control subjects
      (77.8% with hyperlipidemia) without diabetes or statin use. Their cognitive
      functions (attention, memory, and executive functions) were evaluated with the
      trail making test, controlled oral word association test (COWAT), Rey-Osterrieth
      complex figure test, brain damage test (diagnosticum fur cerebralschadigung,
      DCS), Wisconsin card sorting test (WCST), and digit span and block design tests
      from the revised Wechsler adult intelligence scale. RESULTS: Cognitive
      performance was impaired in DM1 patients when compared with the control group
      with regard to semantic verbal fluency (COWAT_animals), visual learning (DCS),
      conceptual-level responses, executive functions (WCST random errors), and WCST
      trials to complete the first category. Subgroups of DM1 patients distinguished on
      the basis of statin therapy did not differ with regard to verbal fluency
      (COWAT_animals), visual learning (DCS), conceptual-level responses, executive
      functions (WCST random errors), and WCST trials to complete the first category.
      Multivariate analysis also does not show the impact of statin therapy on
      cognitive functioning regardless of the duration of education, microangiopathic
      evidence, the presence of hyperlipidemia, or antihypertensive therapy.
      CONCLUSIONS: We find impairment of cognitive functions in DM1 patients when
      compared with control subjects without diabetes. However, we show neither the
      effect of statins nor the significant influence of metabolic control,
      microangiopathic complications, or the presence of hyperlipidemia on cognitive
      functions in DM1 patients.

PMID- 27046663
TI  - Synthesis and characterization of an HSP27-targeted nanoprobe for in vivo
      photoacoustic imaging of early nerve injury.
AB  - Imaging is routinely used for clinical and diagnostic purposes, but techniques
      capable of high specificity and resolution for the early detection of nerve
      injury are still limited. In this study, we found that heat shock protein 27
      (HSP27) becomes highly upregulated within 3 to 7 days of nerve injury. Taking
      advantage of this expression pattern, we conjugated gold nanorods (GNRs) to HSP27
      specific antibodies to generate a nanoprobe (GNR-HSP27Abs) that could be targeted
      to the site of nerve injury and detected by near-infrared photoacoustic imaging.
      Notably, photoacoustic images acquired 12hours after local administration of GNR
      HSP27Abs demonstrated that the nanoprobe can distinguish between injured and
      uninjured nerves in rats. Taken together, these findings expand the application
      of nanoprobe-targeted photoacoustic imaging to the detection of injured nerves,
      and prompt further development of this novel imaging platform for clinical
      application.

PMID- 27046664
TI  - Dissociation mediates the relationship between childhood maltreatment and
      subclinical psychosis.
AB  - More than a third of the population report childhood adversity, and these
      experiences are associated with an increased risk of clinical and subclinical
      psychosis. The reason why some people go on to develop mental health problems and
      others do not is a key question for study. It has been hypothesized that
      dissociative processes mediate the relationship between early adversity and
      psychosis. The current study assessed whether dissociation, and specifically
      depersonalization (one component of dissociation), plays a mediating role in the
      relationship between childhood maltreatment and both hallucination proneness and
      delusional ideation. The study used a cross-sectional design and recruited a
      student sample to assess these relationships in a nonclinical group. Dissociation
      mediated the relationship between early maltreatment and both hallucination
      proneness and delusional ideation. In terms of specific dissociative processes,
      depersonalization did not mediate hallucination proneness or delusional ideation.
      Absorption mediated hallucination proneness; dissociative amnesia (negatively)
      and absorption mediated delusional ideation. It is likely that dissociation
      interferes with the encoding of traumatic information in nonclinical as well as
      clinical groups and in certain ways. Absorption may be particularly relevant. For
      some people, traumatic memories may intrude into conscious awareness in adulthood
      as psychotic-type experience.

PMID- 27046665
TI  - Structural basis for the membrane association of ankyrinG via palmitoylation.
AB  - By clustering various ion channels and transporters, ankyrin-G (AnkG) configures
      the membrane-excitation platforms in neurons and cardiomyocytes. AnkG itself
      localizes to specific areas on the plasma membrane via s-palmitoylation of Cys.
      However, the structural mechanism by which AnkG anchors to the membrane is not
      understood. In this study, we solved the crystal structures of the reduced and
      oxidized forms of the AnkG s-palmitoylation domain and used multiple long-term
      coarse-grained molecular dynamics simulations to analyze their membrane
      association. Here we report that the membrane anchoring of AnkG was facilitated
      by s-palmitoylation, defining a stable binding interface on the lipid membrane,
      and that AnkG without s-palmitoylation also preferred to stay near the membrane
      but did not have a unique binding interface. This suggests that AnkG in the
      juxtamembrane region is primed to accept lipid modification at Cys, and once that
      happens AnkG constitutes a rigid structural base upon which a membrane-excitation
      platform can be assembled. 

PMID- 27046666
TI  - Chaos based crossover and mutation for securing DICOM image.
AB  - This paper proposes a novel encryption scheme based on combining multiple chaotic
      maps to ensure the safe transmission of medical images. The proposed scheme uses
      three chaotic maps namely logistic, tent and sine maps. To achieve an efficient
      encryption, the proposed chao-cryptic system employs a bio-inspired crossover and
      mutation units to confuse and diffuse the Digital Imaging and Communications in
      Medicine (DICOM) image pixels. The crossover unit extensively permutes the image
      pixels row-wise and column-wise based on the chaotic key streams generated from
      the Combined Logistic-Tent (CLT) system. Prior to mutation, the pixels of the
      crossed over image are decomposed into two images with reduced bit depth. The
      decomposed images are then mutated by XOR operation with quantized chaotic
      sequences from Combined Logistic-Sine (CLS) system. In order to validate the
      sternness of the proposed algorithm, the developed chao-cryptic scheme is
      subjected to various security analyses such as statistical, differential, key
      space, key sensitivity, intentional cropping attack and chosen plaintext attack
      analyses. The experimental results prove the proposed DICOM cryptosystem has
      achieved a desirable amount of protection for real time medical image security
      applications.

PMID- 27046667
TI  - Isotope Labeling Study of Retinal Chromophore Fragmentation.
AB  - Previous studies have shown that the gas-phase fragmentation of the retinal
      chromophore after S0-S1 photoexcitation results in a prominent fragment of mass
      248 which cannot be explained by the cleavage of any single bond along the
      polyene chain. It was therefore theorized that the fragmentation mechanism
      involves a series of isomerizations and cyclization processes, and two mechanisms
      for these processes were suggested. Here we used isotope labeling MS-MS to
      provide conclusive support for the fragmentation mechanism suggested by Coughlan
      et al. (J. Phys. Chem. Lett. 2014, 5, 3195).

PMID- 27046668
TI  - Feasibility, acceptability, and potential efficacy of the PTSD Coach app: A pilot
      randomized controlled trial with community trauma survivors.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) is a major public health concern.
      Although effective treatments exist, affected individuals face many barriers to
      receiving traditional care. Smartphones are carried by nearly 2 thirds of the
      U.S. population, offering a promising new option to overcome many of these
      barriers by delivering self-help interventions through applications (apps). As
      there is limited research on apps for trauma survivors with PTSD symptoms, we
      conducted a pilot feasibility, acceptability, and potential efficacy trial of
      PTSD Coach, a self-management smartphone app for PTSD. METHOD: A community sample
      of trauma survivors with PTSD symptoms (N = 49) were randomized to 1 month using
      PTSD Coach or a waitlist condition. Self-report assessments were completed at
      baseline, postcondition, and 1-month follow-up. Following the postcondition
      assessment, waitlist participants were crossed-over to receive PTSD Coach.
      RESULTS: Participants reported using the app several times per week, throughout
      the day across multiple contexts, and endorsed few barriers to use. Participants
      also reported that PTSD Coach components were moderately helpful and that they
      had learned tools and skills from the app to manage their symptoms. Between
      conditions effect size estimates were modest (d = -0.25 to -0.33) for PTSD
      symptom improvement, but not statistically significant. CONCLUSIONS: Findings
      suggest that PTSD Coach is a feasible and acceptable intervention. Findings
      regarding efficacy are less clear as the study suffered from low statistical
      power; however, effect size estimates, patterns of within group findings, and
      secondary analyses suggest that further development and research on PTSD Coach is
      warranted. (PsycINFO Database Record

PMID- 27046669
TI  - Maladaptive trauma appraisals mediate the relation between attachment anxiety and
      PTSD symptom severity.
AB  - OBJECTIVE: In a large sample of community-dwelling older adults with histories of
      exposure to a broad range of traumatic events, we examined the extent to which
      appraisals of traumatic events mediate the relations between insecure attachment
      styles and posttraumatic stress disorder (PTSD) symptom severity. METHOD:
      Participants completed an assessment of adult attachment, in addition to measures
      of PTSD symptom severity, event centrality, event severity, and ratings of the A1
      PTSD diagnostic criterion for the potentially traumatic life event that bothered
      them most at the time of the study. RESULTS: Consistent with theoretical
      proposals and empirical studies indicating that individual differences in adult
      attachment systematically influence how individuals evaluate distressing events,
      individuals with higher attachment anxiety perceived their traumatic life events
      to be more central to their identity and more severe. Greater event centrality
      and event severity were each in turn related to higher PTSD symptom severity. In
      contrast, the relation between attachment avoidance and PTSD symptoms was not
      mediated by appraisals of event centrality or event severity. Furthermore,
      neither attachment anxiety nor attachment avoidance was related to participants'
      ratings of the A1 PTSD diagnostic criterion. CONCLUSION: Our findings suggest
      that attachment anxiety contributes to greater PTSD symptom severity through
      heightened perceptions of traumatic events as central to identity and severe.
      (PsycINFO Database Record

PMID- 27046670
TI  - Supplemental nicotine preloading for smoking cessation in posttraumatic stress
      disorder: Results from a randomized controlled trial.
AB  - BACKGROUND: Individuals with posttraumatic stress disorder (PTSD) are more likely
      to smoke and more likely to relapse following a quit attempt than individuals
      without PTSD. Thus, there is a significant need to study promising interventions
      that might improve quit rates for smokers with PTSD. One such intervention,
      supplemental nicotine patch-preloading, entails the use of nicotine replacement
      therapy prior to quitting. Objective The objective of this study was to conduct a
      randomized controlled trial of the efficacy of supplemental nicotine patch
      preloading among smokers with PTSD. We hypothesized that, relative to
      participants in the placebo condition, participants in the nicotine patch
      preloading condition would: (1) smoke less and experience reduced craving for
      cigarettes during the nicotine patch-preloading phase; (2) experience less
      smoking-associated relief from PTSD symptoms and negative affect during the
      preloading phase; and (3) exhibit greater latency to lapse, and higher short- and
      long-term abstinence rates. METHODS: Sixty-three smokers with PTSD were
      randomized to either nicotine or placebo patch for three weeks prior to their
      quit date. Ecological momentary assessment was used to assess craving, smoking,
      PTSD symptoms, and negative affect during the preloading period. RESULTS:
      Nicotine patch-preloading failed to reduce smoking or craving during the
      preloading phase, nor was it associated with less smoking-associated relief from
      PTSD symptoms and negative affect. Moreover, no differences were observed between
      the treatment conditions for time to lapse, 6-week abstinence, or 6-month
      abstinence. CONCLUSIONS: The findings from the present research suggest that
      supplemental nicotine patch-preloading is unlikely to substantially enhance quit
      rates among smokers with PTSD.

PMID- 27046671
TI  - Marine Bioinspired Underwater Contact Adhesion.
AB  - Marine mussels and barnacles are sessile biofouling organisms that adhere to a
      number of surfaces in wet environments and maintain remarkably strong bonds.
      Previous synthetic approaches to mimic biological wet adhesive properties have
      focused mainly on the catechol moiety, present in mussel foot proteins (mfps),
      and especially rich in the interfacial mfps, for example, mfp-3 and -5, found at
      the interface between the mussel plaque and substrate. Barnacles, however, do not
      use Dopa for their wet adhesion, but are instead rich in noncatecholic aromatic
      residues. Due to this anomaly, we were intrigued to study the initial contact
      adhesion properties of copolymerized acrylate films containing the key
      functionalities of barnacle cement proteins and interfacial mfps, for example,
      aromatic (catecholic or noncatecholic), cationic, anionic, and nonpolar residues.
      The initial wet contact adhesion of the copolymers was measured using a probe
      tack testing apparatus with a flat-punch contact geometry. The wet contact
      adhesion of an optimized, bioinspired copolymer film was ~15.0 N/cm(2) in
      deionized water and ~9.0 N/cm(2) in artificial seawater, up to 150 times greater
      than commercial pressure-sensitive adhesive (PSA) tapes (~0.1 N/cm(2)).
      Furthermore, maximum wet contact adhesion was obtained at ~pH 7, suggesting
      viability for biomedical applications.

PMID- 27046672
TI  - Pressure-Dependent Photoluminescence Study of Wurtzite InP Nanowires.
AB  - The elastic properties of InP nanowires are investigated by photoluminescence
      measurements under hydrostatic pressure at room temperature and experimentally
      deduced values of the linear pressure coefficients are obtained. The pressure
      induced energy shift of the A and B transitions yields a linear pressure
      coefficient of alphaA = 88.2 +/- 0.5 meV/GPa and alphaB = 89.3 +/- 0.5 meV/GPa
      with a small sublinear term of betaA = betaB = -2.7 +/- 0.2 meV/GPa(2). Effective
      hydrostatic deformation potentials of -6.12 +/- 0.04 and -6.2 +/- 0.04 eV are
      derived from the results for the A and B transitions, respectively. A decrease of
      the integrated intensity is observed above 0.5 GPa and is interpreted as a
      carrier transfer from the first to the second conduction band of the wurtzite
      InP.

PMID- 27046673
TI  - Simulation of High Density Lipoprotein Behavior on a Few Layer Graphene
      Undergoing Non-Uniform Mechanical Load.
AB  - Effect of a nonuniform external mechanical load on high density lipoprotein (HDL)
      in aqueous medium was investigated using course-grained molecular dynamics
      simulations. The nonuniform load was achieved by a few layer graphene on one side
      and closed single-walled carbon nanotube (SWNT) (7, 7) on the opposite side of
      lipoprotein. The tube had a diameter of 1 nm and was oriented perpendicularly to
      the graphene. HDL was located between them. The tube was approaching to HDL on
      graphene deforming it. We considered two cases of the tube movement with
      velocities of 20 and 5 m/s. Coarse-grained (CG) molecular dynamics with
      application of the MARTINI force field for HDL and coarse-grained model with an
      all-atom (AA)/CG mapping ratio of 1.5 for carbon nanotube (CNT) (each CG bead was
      modeled by the 4-site CG benzene) were used. Coarse-grained model of HDL was
      received by method of self-assembly. HDL was static but not fixed that gave the
      possibility to compensate its external influence in some way. It was established
      that in water medium HDL interacted with graphene substrate. It was established
      that in water HDL interacts with graphene substrate, slightly flattening but
      retaining its shape of the whole. It was also observed that during the
      calculations HDL partially dodged nanotube. Lipoprotein belts unfolded on the
      graphene substrate in the way of the best compensation for the impact of
      nanotubes. Finally, we observed that the approaching tube has passed through the
      less dense medium of dipalmitoylphosphatidylcholine (DPPC) and its pressure on
      the macromolecule decreased. Inhomogeneity of the external exposure deformed HDL
      at approximately 10-50%. The character of deformation demonstrated that
      lipoprotein has viscoelastic properties similar to a fluid. The discovered
      ability of lipoprotein may help to establish mechanism of interaction of
      lipoproteins with arterial walls and dynamic behavior of lipoproteins in arterial
      intima.

PMID- 27046674
TI  - Screening for Chronic Obstructive Pulmonary Disease: D Is the New F.

PMID- 27046675
TI  - An optimal hydrogen-bond surrogate for alpha-helices.
AB  - Substitution of a main chain i -> i + 4 hydrogen bond with a covalent bond can
      nucleate and stabilize the alpha-helical conformation in peptides. Herein we
      describe the potential of different alkene isosteres to mimic intramolecular
      hydrogen bonds and stabilize alpha-helices in diverse peptide sequences. 

PMID- 27046676
TI  - Investigation of the association between IL10 gene polymorphisms and Vogt
      Koyanagi-Harada disease in a Japanese population.

PMID- 27046677
TI  - Frontlines: It's Not the Same Old Wireless Anymore.

PMID- 27046680
TI  - Ten Questions With ....

PMID- 27046682
TI  - Ask George.

PMID- 27046683
TI  - Making Wireless Work: A Look at What Hospitals Are Doing.
AB  - Three events in January 2016 did a terrific job of capturing the essence of
      wireless technology in healthcare today, putting the expectations, innovations,
      and problems in the limelight. In glitzy Las Vegas, more than 150,000 people
      flocked to CES (formerly the Consumer Electronics Show) and the colocated Digital
      Health Summit. An equally engaged crowd of 1,000+ health information technology
      (IT) and healthcare technology management (HTM) professionals gathered in
      Cleveland for the IHE North American Connectathon. 

PMID- 27046684
TI  - Understanding Higher Education Accreditation for the HTM Field.

PMID- 27046685
TI  - Case Study: Reducing Interruption Fatigue through Improved Alarm Support.

PMID- 27046686
TI  - Understanding Caregiver Workflows: A Proposal for Alarm Condition Priorities.

PMID- 27046687
TI  - Why Benchmarking Is Important to Sterile Processing.

PMID- 27046688
TI  - A Roundtable Discussion: Forging a Path toward Seamless Health IT.

PMID- 27046689
TI  - Clinical Nurse Specialists Play Key Role in Effective Use of Medical Technology.

PMID- 27046690
TI  - Training Advances Biomeds IT Service Skills.

PMID- 27046691
TI  - Increased Complexity Means Trickier Telemetry Problems.

PMID- 27046693
TI  - Hone Your Skills by 'Taking Five'.

PMID- 27046694
TI  - Hospitals Need to Help Industry Keep Improving Healthcare Technology.

PMID- 27046696
TI  - Analysis of ochratoxin A in dried blood spots - Correlation between venous and
      finger-prick blood, the influence of hematocrit and spotted volume.
AB  - We report the improvement of a method for the detection of ochratoxin A (OTA) and
      its thermal degradation product 2'R-ochratoxin A in dried blood spots (DBS) by
      high performance liquid chromatographic (HPLC) tandem mass spectrometry (MS/MS).
      The DBS technique was advanced for the analysis of these two compounds in DBS
      with unknown amounts of blood as well as varying hematocrit values. Furthermore
      the comparability of venous vs. capillary blood was investigated. Human whole
      blood samples were spotted, dried, and extracted with a solvent consisting of
      acetone, acetonitrile and water for analysis by HPLC-MS/MS. Quantification was
      carried out by stable isotope labelled internal standards. Blood samples of
      volunteers (n=50) were used to further optimize and simplify the procedure.
      Ochratoxin A and 2'R-ochratoxin A concentrations found in the entire spots
      (approx. 100 MUL blood) were compared with punched DBS discs of 8.8mm size
      containing approximately 20 MUL blood. As a result the amounts of both toxins in
      a punched 8.8mm disc correlate well with the entire DBS. Also the use of
      capillary blood from finger-pricks versus venous blood was evaluated. The analyte
      levels correlate as well indicating that the less invasive finger-prick sampling
      gives also reliable results. The influence of hematocrit was investigated in a
      range of 25-55% according to the hematocrit in the used real blood samples (34
      46% hematocrit). However no significant hematocrit effect was observed for the
      utilized real blood samples. Moreover different blood volumes were spotted and
      punched as a minimal spot size is usually recommended for accurate analysis. In
      this experiment finger-prick samples typically consist of about 90 MUL blood.
      Therefore spots of 75, 100 and 125 MUL blood were prepared and analyzed. Similar
      to the hematocrit effect, no considerable influence was observed.

PMID- 27046697
TI  - Prognostic instrument for survival outcome in melanoma patients: based on data
      from the population-based Swedish Melanoma Register.
AB  - BACKGROUND: Several major analyses have identified a consistent set of
      independent risk factors for cutaneous malignant melanoma (CMM). A few prognostic
      models have been presented but some are based on a limited number of patients and
      others are based on selected groups of patients referred to major institutions.
      No nationwide population-based prognostic instrument for survival of CMM has been
      presented. The Swedish Melanoma Register (SMR) database covers 99% of CMM
      diagnosed in Sweden and includes today >50,000 cases. OBJECTIVES: To create a
      prognostic instrument based on SMR data to give highly reliable risk profiles for
      patients diagnosed with localised CMM. METHODS: Clinicopathological data were
      linked to the cause of death registry for calculation of CMM-specific survival. A
      generalised gamma method was used to derive 1, 5 and 10year probabilities of
      death for each combination of patient and tumour data: age, sex, tumour site,
      tumour thickness, tumour ulceration, Clark's level of invasion and when
      applicable also outcome of sentinel node biopsy (SNB). RESULTS: Tumour thickness
      had the highest prognostic impact, explaining 77% of the model. Women had 30%
      lower risk of death because of CMM than men. Presence of ulceration nearly
      doubled the risk. If the patient had a positive SNB status the risk of death due
      to CMM increased three times versus a negative SNB status. CONCLUSION: This
      unique population-based prognostic model for primary CMM shows better survival
      than the American Joint Commission on Cancer prognostic model widely used. The
      reason is probably that the referral bias is eliminated in a population-based
      cohort.

PMID- 27046698
TI  - Embryonic atrazine exposure alters zebrafish and human miRNAs associated with
      angiogenesis, cancer, and neurodevelopment.
AB  - MicroRNAs (miRNAs) are short, single-stranded RNA that regulate post
      transcriptional control of mRNA translation. Knowledge on the role of these
      critical regulators in toxicological responses in increasing, but is still
      limited. Atrazine is a herbicide used throughout the Midwestern US that is
      reported to frequently contaminate potable water supplies above the maximum
      contaminant level of 3 parts per billion. Atrazine is a suspected endocrine
      disrupting chemical and studies have begun to investigate the genetic mechanisms
      of toxicity; however, studies investigating epigenetic mechanisms are limited. In
      this study both zebrafish and human miRNAs were significantly altered in response
      to an embryonic atrazine exposure of 0.3, 3, or 30 ppb in zebrafish. Altered
      miRNAs are known to play a role in angiogenesis, cancer, or neuronal development,
      differentiation, and maturation. Targeted analysis of altered human miRNAs with
      genes previously identified to be altered by atrazine exposure revealed several
      targets linked to cell cycle and cell signaling. Further analysis of hsa-miRNA
      126-3p, which had altered expression in all three atrazine treatments at 72 hpf,
      revealed alterations also occurred at 60 hpf in the 30 ppb treatment group.
      Results from this study indicate miRNA deregulation in zebrafish and human miRNAs
      following an embryonic atrazine exposure in zebrafish.

PMID- 27046699
TI  - Strategy for identifying unknown hemoglobin adducts using adductome LC-MS/MS
      data: Identification of adducts corresponding to acrylic acid, glyoxal,
      methylglyoxal, and 1-octen-3-one.
AB  - Electrophilic compounds have the ability to form adducts with nucleophilic sites
      in proteins and DNA in tissues, and thereby constitute risks for toxic effects.
      Adductomic approaches are developed for systematic screening of adducts to DNA
      and blood proteins, with the aim to detect unknown internal exposures to
      electrophiles. In a previous adductomic screening of adducts to N-terminals in
      hemoglobin, using LC-MS/MS, 19 unknown adducts were detected in addition to seven
      previously identified adducts. The present paper describes the identification of
      four of these unknown adducts, as well as the strategy used to identify them.
      Using LC-MS data from the screening, hypotheses about adduct identities were
      formulated: probable precursor electrophiles with matching molecular weights were
      suggested based on the molecular weights of the modifications and the retention
      times of the analytes, in combination with comparisons of theoretical Log P
      calculations and databases. Reference adducts were generated by incubation of
      blood samples with the hypothesized precursor electrophiles. The four identified
      precursor electrophiles, corresponding to the observed unknown adducts, were
      glyoxal, methylglyoxal, acrylic acid and 1-octen-3-one. Possible origins/exposure
      sources and toxicological information concerning the electrophilic precursors are
      discussed. The identified adducts could be explored as possible biomarkers for
      exposure. 

PMID- 27046700
TI  - Safety of laparoscopic cholecystectomy after coronary artery bypass with the
      right gastroepiploic artery.

PMID- 27046701
TI  - The tunics of Glisson.

PMID- 27046702
TI  - Defining when to offer operative treatment for intrahepatic cholangiocarcinoma: A
      regret-based decision curves analysis.
AB  - BACKGROUND: Regret-based decision curve analysis (DCA) is a framework that
      assesses the medical decision process according to physician attitudes (expected
      regret) relative to disease-based factors. We sought to apply this methodology to
      decisions around the operative management of intrahepatic cholangiocarcinoma
      (ICC). METHODS: Utilizing a multicentric database of 799 patients who underwent
      liver resection for ICC, we developed a prognostic nomogram. DCA tested 3
      strategies: (1) perform an operation on all patients, (2) never perform an
      operation, and (3) use the nomogram to select patients for an operation. RESULTS:
      Four preoperative variables were included in the nomogram: major vascular
      invasion (HR = 1.36), tumor number (multifocal, HR = 1.18), tumor size (>5 cm, HR
      = 1.45), and suspicious lymph nodes on imaging (HR = 1.47; all P < .05). The
      regret-DCA was assessed using an online survey of 50 physicians, expert in the
      treatment of ICC. For a patient with a multifocal ICC, largest lesion measuring
      >5 cm, one suspicious malignant lymph node, and vascular invasion on imaging, the
      1-year predicted survival was 52% according to the nomogram. Based on the
      therapeutic decision of the regret-DCA, 60% of physicians would advise against an
      operation for this scenario. Conversely, all physicians recommended an operation
      to a patient with an early ICC (single nodule measuring 3 cm, no suspicious lymph
      nodes, and no vascular invasion at imaging). CONCLUSION: By integrating a
      nomogram based on preoperative variables and a regret-based DCA, we were able to
      define the elements of how decisions rely on medical knowledge (postoperative
      survival predicted by a nomogram, severity disease assessment) and physician
      attitudes (regret of commission and omission).

PMID- 27046703
TI  - Progress towards achieving global tuberculosis control: so near, yet so far.

PMID- 27046704
TI  - Tuberculosis prevention and control: we need to pay heed to diabetes care.

PMID- 27046705
TI  - Tobacco control in India: where are we?

PMID- 27046706
TI  - The challenge of personalised care for all in chronic obstructive pulmonary
      disease.

PMID- 27046707
TI  - Drug-resistant tuberculosis clinical trials: proposed core research definitions
      in adults.
AB  - Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for
      the first time in decades, new drugs for the treatment of this disease have been
      developed. These new drugs have prompted strengthened efforts in DR-TB clinical
      trials research, and there are now multiple ongoing and planned DR-TB clinical
      trials. To facilitate comparability and maximise policy impact, a common set of
      core research definitions is needed, and this paper presents a core set of
      efficacy and safety definitions as well as other important considerations in DR
      TB clinical trials work. To elaborate these definitions, a search of clinical
      trials registries, published manuscripts and conference proceedings was
      undertaken to identify groups conducting trials of new regimens for the treatment
      of DR-TB. Individuals from these groups developed the core set of definitions
      presented here. Further work is needed to validate and assess the utility of
      these definitions but they represent an important first step to ensure there is
      comparability in clinical trials on multidrug-resistant TB. 

PMID- 27046708
TI  - Market assessment of tuberculosis diagnostics in China in 2012.
AB  - OBJECTIVE: To assess the 2012 served available market for tuberculosis (TB)
      diagnostics in China in the sector served by the China Centre for Disease Control
      and Prevention (CDC) and the hospital sector in China, including both designated
      TB hospitals and general hospitals. DESIGN: Test volumes and unit costs were
      assessed for tuberculin skin tests, interferon-gamma release assays (IGRAs),
      smear microscopy, serology, cultures, speciation tests, nucleic-acid
      amplification tests (NAATs), drug susceptibility tests and adenosine-deaminase
      tests (ADA). Data were obtained from electronic databases (CDC sector) and
      through surveys (hospital sector), and were estimated for the two sectors and for
      the country as a whole. Test costs were estimated by staff at China CDC, and
      using published literature. RESULTS: In 2012, the China CDC and hospital sectors
      performed a total of 44 million TB diagnostic tests at an overall value of US$294
      million. Tests used by the CDC sector were smear microscopy, solid and liquid
      culture and DST, while the hospital sector also used IGRAs, NAATs, ADA and
      serology. The hospital sector accounted for 76% of the overall test volume and
      94% of the market value. CONCLUSION: China has a very large TB diagnostic market
      that encompasses a wide range of diagnostic tests, with the majority being
      performed in Chinese hospitals.

PMID- 27046709
TI  - Market assessment of tuberculosis diagnostics in India in 2013.
AB  - BACKGROUND: India represents a significant potential market for new tests. We
      assessed India's market for tuberculosis (TB) diagnostics in 2013. METHODS: Test
      volumes and unit costs were assessed for tuberculin tests, interferon-gamma
      release assays, sputum smear microscopy, serology, culture, speciation testing,
      nucleic-acid amplification tests (i.e., in-house polymerase chain reaction,
      Xpert((r)) MTB/RIF, line-probe assays) and drug susceptibility testing. Data from
      the public sector were collected from the Revised National TB Control Programme
      reports. Private sector data were collected through a survey of private
      laboratories and practitioners. Data were also collected from manufacturers.
      RESULTS: In 2013, India's public sector performed 19.2 million tests, with a
      market value of US$22.9 million. The private sector performed 13.6 million tests,
      with a market value of US$60.4 million when prices charged to the patient were
      applied. The overall market was US$70.8 million when unit costs from the
      ingredient approach were used for the 32.8 million TB tests performed in the
      entire country. Smear microscopy was the most common test performed, accounting
      for 25% of the overall market value. CONCLUSION: India's estimated market value
      for TB diagnostics in 2013 was US$70.8 million. These data should be of relevance
      to test developers, donors and implementers.

PMID- 27046710
TI  - Validation of smear-positive tuberculosis diagnoses in Bangladesh.
AB  - SETTING: Questions have been raised as to the accuracy of smear-positive
      tuberculosis (TB) diagnoses at DOTS centres in Bangladesh. OBJECTIVE: To assess
      the validity of diagnoses by smear microscopy at 62 DOTS centres in various
      health facilities. DESIGN: Using a cross-sectional study design, smear-positive
      TB cases were included from high, medium and low-performing DOTS centres from
      July to December 2010. The centres were categorised according to their case
      detection rate: centres with case detection rates of >70%, 50-70% and <50% were
      classed as high, medium and low-performing, respectively. Microscopy was
      performed on spot and early morning sputum samples for all cases. RESULTS: A
      convenience sample of 333 recently diagnosed smear-positive TB cases was
      included. The average number of patients enrolled per centre was 5.4; the highest
      number of cases was diagnosed from low-performing DOTS centres. Of the 333 cases,
      302 (90.7%) were confirmed, while 31 (9.3%) were smear-negative. CONCLUSION:
      Differences in microscopy results could be due to the poor quality of the sputum
      sample, of smearing, staining or reading, or erroneous reporting by the DOTS
      centres. Preset programme targets and the nationwide drug stockout may have led
      to overreporting by the DOTS centres.

PMID- 27046711
TI  - The role of macroscopic sputum quality assessments to optimise sputum testing for
      tuberculosis.
AB  - SETTING: Community-wide active case finding for tuberculosis (TB) using Xpert(r)
      MTB/RIF as the primary screening tool, Ca Mau Province, Viet Nam. OBJECTIVES: To
      determine whether macroscopic sputum quality characteristics (sputum colour and
      volume) can be used to predict Xpert MTB-negative sputum and hence exclude sputum
      samples from testing. DESIGN: Field staff conducted household visits to
      approximately 51,200 adults in 58 villages randomly selected from throughout the
      province. Sputum samples from all screened participants who were able to produce
      ?1 ml sputum underwent macroscopic sputum assessment and were tested with Xpert.
      RESULTS: Of the 21,624 sputum samples tested, 159 (0.74%) were Xpert MTB
      positive; 93% of the samples were 1-2 ml and nearly all were mucoid (93%) or
      mucopurulent (5.7%). One salivary sample was Xpert MTB-positive (2.0% of all
      salivary samples). The lowest positive predictive value for any sputum volume or
      colour characteristic was 0.66%. This was not substantially different from the
      overall prevalence of positive sputum Xpert MTB (0.74%). CONCLUSION: Sputum
      colour and volume cannot be used to predict the presence or absence of M.
      tuberculosis in sputum detected using Xpert. These sputum quality parameters
      cannot therefore be used to exclude sputum samples from testing for TB.

PMID- 27046712
TI  - Direct tuberculosis drug susceptibility testing: time-saving and cost-effective
      in detecting MDR-TB.
AB  - BACKGROUND: Recent advances have made molecular diagnosis of tuberculosis (TB)
      and drug susceptibility testing (DST) possible, but the high costs involved
      present a huge challenge. The refinement and improvement of affordable methods
      therefore remain a priority. Conventional indirect DST is inexpensive and
      reliable, but time-consuming. A direct DST method for the direct testing of
      sputum samples without culture has been developed to reduce the time required for
      DST, but there have been conflicting results. METHODS AND RESULTS: Direct and
      indirect DST against isoniazid and rifampicin were performed on 208 sputum smear
      positive specimens, 186 from newly diagnosed patients and 22 from previously
      treated patients; respectively 169 and 180 of the direct and indirect DST results
      were reportable. In comparison with indirect DST, direct DST resulted in a saving
      of on average 10.5 days. The time to direct DST results was inversely correlated
      with the number of acid-fast bacilli in the sputum samples. CONCLUSION: Direct
      DST is highly sensitive, reliable, cost-effective and time-saving in comparison
      with indirect DST.

PMID- 27046713
TI  - Sensititre(r) MYCOTB MIC plate for drug susceptibility testing of Mycobacterium
      tuberculosis complex isolates.
AB  - SETTING: National Tuberculosis Clinical Laboratory, China. OBJECTIVE: To evaluate
      the accuracy and feasibility of the MYCOTB MIC plate in anti-tuberculosis drug
      susceptibility testing. DESIGN: MYCOTB testing of Mycobacterium tuberculosis
      isolates, the Lowenstein-Jensen (LJ) proportion method and the resurazine
      microtitre assay (REMA), which is extensively used for in-house assay for minimal
      inhibition concentration (MIC) testing, were performed simultaneously for
      comparison. A total of 126 clinical isolates were tested using both MYCOTB and
      the LJ proportion method against 12 anti-tuberculosis drugs; 80 were also tested
      using REMA. RESULTS: Categorical agreement between MYCOTB and the LJ proportion
      method was 99.2% for rifampicin, ofloxacin, amikacin, kanamycin and cycloserine,
      and 98.4% for isoniazid and para-aminosalicylic acid; ethambutol (EMB) had the
      lowest agreement (86.5%). The overall categorical agreement between MYCOTB and
      REMA ranged between 98.8% and 100%. MYCOTB outcomes, interpreted on day 10 and
      21, were stable for all drugs except EMB. CONCLUSION: MYCOTB is a rapid,
      convenient, quantitative and accurate method for testing both first- and second
      line anti-tuberculosis drugs.

PMID- 27046714
TI  - Remote monitoring of Xpert(r) MTB/RIF testing in Mozambique: results of
      programmatic implementation of GxAlert.
AB  - SETTING: Electronic diagnostic tests, such as the Xpert(r) MTB/RIF assay, are
      being implemented in low- and middle-income countries (LMICs). However, timely
      information from these tests available via remote monitoring is underutilized.
      The failure to transmit real-time, actionable data to key individuals such as
      clinicians, patients, and national monitoring and evaluation teams may negatively
      impact patient care. OBJECTIVE: To describe recently developed applications that
      allow for real-time, remote monitoring of Xpert results, and initial
      implementation of one of these products in central Mozambique. DESIGN: In
      partnership with the Mozambican National Tuberculosis Program, we compared three
      different remote monitoring tools for Xpert and selected one, GxAlert, to pilot
      and evaluate at five public health centers in Mozambique. RESULTS: GxAlert
      software was successfully installed on all five Xpert computers, and test results
      are now uploaded daily via a USB internet modem to a secure online database. A
      password-protected web-based interface allows real-time analysis of test results,
      and 1200 positive tests for tuberculosis generated 8000 SMS result notifications
      to key individuals. CONCLUSION: Remote monitoring of diagnostic platforms is
      feasible in LMICs. While promising, this effort needs to address issues around
      patient data ownership, confidentiality, interoperability, unique patient
      identifiers, and data security.

PMID- 27046715
TI  - Risk factors for Mycobacterium tuberculosis infection in 2-4 year olds in a rural
      HIV-prevalent setting.
AB  - BACKGROUND: Mycobacterium tuberculosis infection in children acts as a sentinel
      for infectious tuberculosis. OBJECTIVE: To assess risk factors associated with
      tuberculous infection in pre-school children. METHOD: We conducted a population
      wide tuberculin skin test (TST) survey from January to December 2012 in Malawi.
      All children aged 2-4 years residing in a demographic surveillance area were
      eligible. Detailed demographic data, including adult human immunodeficiency virus
      (HIV) status, and clinical and sociodemographic data on all diagnosed
      tuberculosis (TB) patients were available. RESULTS: The prevalence of M.
      tuberculosis infection was 1.1% using a TST induration cut-off of 15 mm
      (estimated annual risk of infection of 0.3%). The main identifiable risk factors
      were maternal HIV infection at birth (adjusted OR [aOR] 3.6, 95%CI 1.1-12.2),
      having three or more adult members in the household over a lifetime (aOR 2.4,
      95%CI 1.2-4.8) and living in close proximity to a known case of infectious TB
      (aOR 1.6, 95%CI 1.1-2.4), modelled as a linear variable across categories (>200
      m, 100-200 m, <100 m, within household). Less than 20% of the infected children
      lived within 200 m of a known diagnosed case. CONCLUSION: Household and community
      risk factors identified do not explain the majority of M. tuberculosis infections
      in children in our setting.

PMID- 27046716
TI  - Health care workers' gender bias in testing could contribute to missed
      tuberculosis among women in South Africa.
AB  - SETTING: Eight communities with high tuberculosis (TB) prevalence, Western Cape,
      South Africa. OBJECTIVE: To identify sex differences in TB health-seeking
      behaviour and diagnosis in primary health care facilities and how this influences
      TB diagnosis. DESIGN: We used data from a prevalence survey among 30,017 adults
      conducted in 2010 as part of the Zambia, South Africa Tuberculosis and AIDS
      Reduction (ZAMSTAR) trial. RESULTS: A total of 1670 (5.4%) adults indicated they
      had a cough of ?2 weeks, 950 (56.9%) of whom were women. Women were less likely
      to report a cough of ?2 weeks (5.1% vs. 6.4%, P < 0.001), but were more likely to
      seek care for their cough (32.6% vs. 26.9%, P = 0.012). Of all adults who sought
      care, 403 (80.0%) sought care for their cough at a primary health care (PHC)
      facility (79.0% women vs. 81.4% men, P = 0.511). Women were less likely to be
      asked for a sputum sample at the PHC facility (63.3% vs. 77.2%, P = 0.003) and
      less likely to have a positive sputum result (12.6% vs. 20.7%, P = 0.023).
      CONCLUSION: The attainment of sex equity in the provision of TB health services
      requires adherence to testing protocols. Everyone, irrespective of sex, who seeks
      care for a cough of ?2 weeks should be tested.

PMID- 27046717
TI  - Tuberculosis in native- and foreign-born populations in Portugal.
AB  - BACKGROUND: Tuberculosis (TB) is a major global health problem, and during the
      last 20 years, industrialised countries have shown similar patterns in TB
      notifications: decreasing TB incidence in native populations and increasing
      incidence in foreign-born populations. OBJECTIVES: To characterise risk factors
      associated with TB among native- and foreign-born TB patients in Portugal and
      identify barriers to the management of foreign cases. METHODS: Analysis of the
      data from the national tuberculosis surveillance system and data from an online
      survey of physicians managing TB cases in the country. RESULTS: Risk factors in
      the two populations differed. Foreign-born patients were younger, less likely to
      use drugs or alcohol and had fewer comorbidities. They were also more likely to
      be human immunodeficiency virus positive, to be employed and to be
      homeless/living in shelters. The outcome of the disease and the time to diagnosis
      were not significantly different between the two populations. The most important
      barriers to the management of foreign-born TB cases were language and fear of
      deportation. CONCLUSIONS: As there are significant differences between the two
      populations, different TB control strategies should be implemented in the two
      populations.

PMID- 27046718
TI  - Factors associated with extended treatment among tuberculosis patients at risk of
      relapse in California.
AB  - SETTING: California, United States. OBJECTIVE: To determine the frequency of
      tuberculosis (TB) patients at risk for relapse who received at least 9 months of
      anti-tuberculosis treatment (extended treatment) and to identify factors
      associated with not receiving extended treatment. DESIGN: We analyzed
      characteristics of culture-confirmed pulmonary TB patients reported to the
      California TB Registry during 2004-2009. Patients with cavities on initial chest
      radiograph and delayed culture conversion (?70 days) were at 'high risk of
      relapse', and anti-tuberculosis treatment of ?270 days was 'extended treatment'.
      We used a generalized linear model to identify independent risk factors for
      absence of extended treatment in the high risk of relapse group. RESULTS: Among
      5680 TB patients, 483 (8.5%) were at high risk of relapse: 372 (77%) received
      extended treatment but 111 (23%) did not. Factors associated with absence of
      extended treatment included negative sputum smears (adjusted prevalence ratio
      [aPR] 2.62, 95%CI 1.69-4.05), residence in three specific counties (aPR 1.71,
      95%CI 1.19-2.46) and Black race (aPR 1.56, 95%CI 1.03-2.38). CONCLUSIONS: Nearly
      a quarter of TB patients at high risk of relapse did not receive extended
      treatment. Increased efforts are needed to ensure that all patients who may
      benefit from extended anti-tuberculosis treatment receive it.

PMID- 27046719
TI  - Presumptive treatment of multidrug-resistant tuberculosis in household contacts.
AB  - SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a growing global health
      threat that often requires presumptive treatment in the absence of drug
      susceptibility testing (DST) results. OBJECTIVE: To compare two approaches to the
      treatment of MDR-TB contacts with no DST results who develop TB disease. DESIGN:
      We conducted a retrospective cohort study of adults treated for TB disease who
      were contacts of patients living with MDR-TB. Subjects had been treated according
      to one of two presumptive treatment strategies: 1) regimens containing
      exclusively first-line drugs, and 2) regimens that included both first- and
      second-line drugs that were adjusted if and when DST results became available.
      The primary endpoint was a composite of death and treatment failure. RESULTS:
      Household contacts of MDR-TB patients who developed TB disease and were treated
      with first-line regimens were significantly more likely to experience unfavorable
      end-of-treatment outcomes than those treated with presumptive MDR-TB regimens (RR
      2.88, 95%CI 1.24-6.68). CONCLUSION: Household contacts of MDR-TB patients who
      develop TB disease but have no DST results should receive regimens containing
      second-line drugs selected based on the infecting strain of the index patient.
      Regimens containing only first-line anti-tuberculosis drugs significantly
      increase the risk of unfavorable outcomes.

PMID- 27046720
TI  - Does enhanced diabetes management reduce the risk and improve the outcome of
      tuberculosis?
AB  - SETTING: The Bureau of National Health Insurance (NHI) has implemented a pay-for
      performance (p4p) programme for diabetes mellitus (DM) in Taiwan. OBJECTIVE: To
      investigate whether patients with DM enrolled in the p4p programme (DM-p4p) are
      less likely to develop tuberculosis (TB) and whether they have a better outcome
      than patients with DM not enrolled in the p4p programme (DM-non-p4p) if they do
      develop TB. DESIGN: A random sample of 79,471 DM-p4p, 100,000 DM-non-p4p and
      100,000 non-diabetic patients (non-DM) was obtained from the 2008-2009 NHI
      database, and the patients were matched with the National TB Registry to
      determine whether they had developed TB by the end of 2010. RESULTS: The average
      annual incidence of TB was respectively 259.9 (95%CI 230.2-293.4), 137.5 (95%CI
      116.4-162.5) and 74.1 (95%CI 59.0-93.0) per 100,000 population among DM-non-p4p,
      DM-p4p and non-DM patients. The relative risk of death over treatment success was
      1.79 (95%CI 1.05-3.04) among DM-non-p4p and 1.69 (95%CI 0.84-3.40) among non-DM
      patients, relative to DM-p4p patients. CONCLUSIONS: Enhanced case management of
      DM reduced risk and improved outcomes of TB among patients with DM.

PMID- 27046721
TI  - Vitamin D and tuberculosis: review and association in three rural provinces of
      Afghanistan.
AB  - OBJECTIVES: 1) To update the 2006 systematic review and meta-analysis by Nnoaham
      & Clarke exploring the association between serum vitamin D and risk of active
      tuberculosis (TB) following discrepant evidence; and 2) to identify whether TB
      and vitamin D are associated in rural Afghanistan. METHODS: Systematic review and
      meta-analysis of studies published between January 1980 and June 2014 using
      Nnoaham & Clarke's methodology. For this case-control study, 90 age- and sex
      matched pairs were recruited from rural provinces, and blood 25-hydroxyvitamin D
      concentrations were measured using enzyme-linked immunosorbent assay. RESULTS:
      Sixteen studies were eligible for review. Eleven showed differences between
      vitamin D levels in TB patients and controls, two showed partial differences and
      three showed none. Studies on African and European populations show lower vitamin
      D levels in TB patients, but results from Asia vary. No significant differences
      were found in vitamin D levels in our rural Afghan population. Controls had a
      higher body mass index (BMI) (mean control BMI 21.50 kg/m(2), mean case BMI 18.86
      kg/m(2), P < 0.001), and were more likely to have been employed (40% of controls,
      15.6% of cases, P = 0.002). CONCLUSION: Genetic differences may account for the
      differences among study results in the systematic review. Vitamin D levels are
      not associated with TB among Afghans living in these rural provinces.

PMID- 27046722
TI  - Risk factors for exacerbation in chronic obstructive pulmonary disease: a
      prospective study.
AB  - BACKGROUND: Although acute exacerbations are key events in the progression of
      chronic obstructive pulmonary disease (COPD), their frequency and the factors
      associated with acute exacerbation are not fully known. OBJECTIVE: To determine
      the incidence and risk factors of very frequent exacerbations in COPD (?3 per
      year). PATIENTS AND METHODS: In a cohort study to analyse acute exacerbation and
      associated factors in 512 primary care patients during a 2-year follow-up,
      variables of interest were collected for each patient. Acute exacerbation was
      defined as an event that required antibiotics and/or systemic steroids (moderate)
      or hospital admission (severe). Odds ratios (OR) were used to determine factors
      associated with exacerbation. RESULTS: Incidence of exacerbation was 61.7% in the
      first year of follow-up and 63.9% in the second year. During the first year, the
      factors associated with very frequent exacerbation were previous hospital
      admission (OR 1.69), dyspnoea (moderate [OR 2.86] and severe-very severe [OR
      5.83]) and the Charlson Index (OR 1.19); during the second year, associated
      factors were female sex (OR 4.17), history of previous hospital admissions (OR
      2.90), smoking (smoker/ex-smoker) (OR 2.00) and forced vital capacity (OR 0.98).
      CONCLUSIONS: Incidence of exacerbation is high in COPD patients. Previous
      admission for exacerbation is a strong predictor and can identify patients at
      risk.

PMID- 27046723
TI  - Risk factors for hospital readmission for COPD after implementation of the GOLD
      guidelines.
AB  - BACKGROUND: Few updated studies have investigated risk factors for readmission
      for chronic obstructive pulmonary disease (COPD) since the implementation of the
      latest treatment guidelines. OBJECTIVE: To evaluate a series of potential risk
      factors for readmission in patients with COPD and in a subgroup with very
      frequent readmissions after implementation of the Global Initiative for Chronic
      Obstructive Lung Disease guidelines. DESIGN: Two hundred and fifty patients
      admitted for acute exacerbation of COPD (AECOPD) were recruited over 1 year. The
      readmission frequency in the ensuing year following hospital discharge was
      recorded and analysed against potential risk factors collected during the index
      admission. RESULTS: In the ensuing year, 183 (73.2%) patients were readmitted at
      least once for AECOPD. Previous non-invasive ventilation for AECOPD (HR 1.56,
      95%CI 1.08-2.26), COPD Assessment Test score (HR 1.03, 95%CI 1.00-1.05), 6-minute
      walk distance (HR 0.98 per 10 m increase, 95%CI 0.97-0.99) and number of
      admissions for AECOPD in the previous year (HR 1.11, 95%CI 1.06-1.16) were
      independently associated with time to first readmission. Subgroup analysis showed
      that anxiety (OR 3.97, 95%CI 1.49-10.57) was strongly associated with very
      frequent readmissions (?4 in 1 year). CONCLUSIONS: AECOPD is associated with high
      rates of readmission. Anxiety is a potential modifiable factor associated with
      very frequent readmissions.

PMID- 27046724
TI  - Unsupervised learning technique identifies bronchiectasis phenotypes with
      distinct clinical characteristics.
AB  - BACKGROUND: Unsupervised learning technique allows researchers to identify
      different phenotypes of diseases with complex manifestations. OBJECTIVES: To
      identify bronchiectasis phenotypes and characterise their clinical manifestations
      and prognosis. METHODS: We conducted hierarchical cluster analysis to identify
      clusters that best distinguished clinical characteristics of bronchiectasis.
      Demographics, lung function, sputum bacteriology, aetiology, radiology, disease
      severity, quality-of-life, cough scale and capsaicin sensitivity, exercise
      tolerance, health care use and frequency of exacerbations were compared. RESULTS:
      Data from 148 adults with stable bronchiectasis were analysed. Four clusters were
      identified. Cluster 1 (n = 69) consisted of the youngest patients with
      predominantly mild and idiopathic bronchiectasis with minor health care resource
      use. Patients in cluster 2 (n = 22), in which post-infectious bronchiectasis
      predominated, had the longest duration of symptoms, greater disease severity,
      poorer lung function, airway Pseudomonas aeruginosa colonisation and frequent
      health care resource use. Cluster 3 (n = 16) consisted of elderly patients with
      shorter duration of symptoms and mostly idiopathic bronchiectasis, and
      predominantly severe bronchiectasis. Cluster 4 (n = 41) constituted the most
      elderly patients with moderate disease severity. Clusters 2 and 3 tended to have
      a greater risk of bronchiectasis exacerbations (P = 0.06) than clusters 1 and 4.
      CONCLUSION: Identification of distinct phenotypes will lead to greater insight
      into the characteristics and prognosis of bronchiectasis.

PMID- 27046725
TI  - Compliance with tobacco control policies in India: an examination of facilitators
      and barriers.
AB  - SETTING: India's Cigarettes and Other Tobacco Products Act (COTPA) prohibits
      smoking in public places, limits advertising at points of sale, and bans sales in
      close proximity to educational institutions. OBJECTIVE: To examine key
      stakeholders' (i.e., tobacco retailers, hotel and restaurant owners/managers, law
      enforcement officials, school principals/administrators) perceptions of
      facilitators and barriers to compliance with COTPA. DESIGN: Using semi-structured
      in-depth interviews (n = 60), we identified a range of facilitators and barriers
      that varied across the venues. RESULTS: A number of simple measures to increase
      compliance were identified: provide signs to retailers, provide aesthetically
      pleasing signs more fitting for the atmosphere of the hotel/restaurant, etc., and
      empower law enforcement to implement the law. CONCLUSIONS: Priority should be
      placed on public awareness, as it can facilitate compliance in numerous venues.
      Communication efforts could be undertaken to change the public's residual
      negative attitudes toward the policy.

PMID- 27046726
TI  - PM2.5 as a marker of exposure to tobacco smoke and other sources of particulate
      matter in Cairo, Egypt.
AB  - SETTING: Cairo and Giza governorates of Egypt. BACKGROUND: Particulate matter
      under 2.5 MUm in diameter (PM2.5) arises from diverse sources, including tobacco
      smoke from cigarettes and waterpipes, and is recognized as a cause of acute and
      chronic morbidity and mortality. OBJECTIVE: To measure PM2.5 in workplaces with
      different intensities of smoking and varying levels of smoking restrictions.
      DESIGN: We conducted an air sampling study to measure PM2.5 levels in a
      convenience sample of indoor and outdoor venues in 2005-2006. RESULTS: Using a
      calibrated SidePak instrument, 3295 individual measurements were collected at 96
      venues. Compared to indoor venues where tobacco smoking was banned (PM2.5 levels
      72-81 MUg/m(3)), places offering waterpipes to patrons of cafes (478 MUg/m(3))
      and Ramadan tents (612 MUg/m(3)) had much higher concentrations, as did venues
      such as public buildings with poor enforcement of smoking restrictions (range 171
      704 MUg/m(3)). Both the number of waterpipe smokers and the number of cigarette
      smokers observed at each venue contributed significantly to the overall burden of
      PM2.5. CONCLUSION: Such data will support smoke-free policies and programs aimed
      specifically at reducing environmental tobacco exposure and improving air quality
      in general, and will provide a baseline for monitoring the impact of tobacco
      control policies.

PMID- 27046727
TI  - The impact of mixed infections on the interpretation of molecular epidemiology
      studies of tuberculosis.

PMID- 27046728
TI  - In reply.

PMID- 27046729
TI  - Time for men to count, too.

PMID- 27046730
TI  - In reply.

PMID- 27046731
TI  - Metagenomic Evidence of the Prevalence and Distribution Patterns of Antimicrobial
      Resistance Genes in Dairy Agroecosystems.
AB  - Antimicrobial resistance (AR) is a global problem with serious implications for
      public health. AR genes are frequently detected on animal farms, but little is
      known about their origin and distribution patterns. We hypothesized that AR genes
      can transfer from animal feces to the environment through manure, and to this
      end, we characterized and compared the resistomes (collections of AR genes) of
      animal feces, manure, and soil samples collected from five dairy farms using a
      metagenomics approach. Resistomes constituted only up to 1% of the total gene
      content, but were variable by sector and also farm. Broadly, the identified AR
      genes were associated with 18 antibiotic resistances classes across all samples;
      however, the most abundant genes were classified under multidrug transporters
      (44.75%), followed by resistance to vancomycin (12.48%), tetracycline (10.52%),
      bacitracin (10.43%), beta-lactam resistance (7.12%), and MLS efflux pump (6.86%)
      antimicrobials. The AR gene profiles were variable between farms. Farm 09 was
      categorized as a high risk farm, as a greater proportion of AR genes were common
      to at least three sectors, suggesting possible horizontal transfer of AR genes.
      Taxonomic characterization of AR genes revealed that a majority of AR genes were
      associated with the phylum Proteobacteria. Nonetheless, there were several
      members of Bacteroidetes, particularly Bacteroides genus and several lineages
      from Firmicutes that carried similar AR genes in different sectors, suggesting a
      strong potential for horizontal transfer of AR genes between unrelated bacterial
      hosts in different sectors of the farms. Further studies are required to affirm
      the horizontal gene transfer mechanisms between microbiomes of different sectors
      in animal agroecosystems.

PMID- 27046732
TI  - In vitro CYP1A activity in the zebrafish: temporal but low metabolite levels
      during organogenesis and lack of gender differences in the adult stage.
AB  - The zebrafish (Danio rerio) is increasingly used as a screening model for acute,
      chronic and developmental toxicity. More specifically, the embryo is currently
      investigated as a replacement of in vivo developmental toxicity studies, although
      its biotransformation capacity remains a point of debate. As the cytochrome P450
      1 (CYP1) family plays an important role in the biotransformation of several
      pollutants and drugs, a quantitative in vitro protocol was refined to assess
      gender- and age-related CYP1A activity in the zebrafish using the ethoxyresorufin
      o-deethylase (EROD) assay. Microsomal protein fractions were prepared from livers
      of adult males and females, ovaries and whole embryo homogenates of different
      developmental stages. A large biological variation but no gender-related
      difference in CYP1A activity was observed in adult zebrafish. Embryos showed
      distinct temporal but low CYP1A activity during organogenesis. These in vitro
      data raise questions on the bioactivation capacity of zebrafish embryos in
      developmental toxicity studies.

PMID- 27046733
TI  - Revision of the ICH guideline on detection of toxicity to reproduction for
      medicinal products: SWOT analysis.
AB  - SWOT analysis was used to gain insights and perspectives into the revision of the
      ICH S5(R2) guideline on detection of toxicity to reproduction for medicinal
      products. The current ICH guideline was rapidly adopted worldwide and has an
      excellent safety record for more than 20 years. The revised guideline should aim
      to further improve reproductive and developmental (DART) safety testing for new
      drugs. Alternative methods to animal experiments should be used whenever
      possible. Modern technology should be used to obtain high quality data from fewer
      animals. Additions to the guideline should include considerations on the
      following: limit dose setting, maternal toxicity, biopharmaceuticals, vaccines,
      testing strategies by indication, developmental immunotoxicity, and male-mediated
      developmental toxicity. Emerging issues, such as epigenetics and the microbiome,
      will most likely pose challenges to DART testing in the future. It is hoped that
      the new guideline will be adopted even outside the ICH regions.

PMID- 27046734
TI  - Monitoring variations of dimethyl sulfide and dimethylsulfoniopropionate in
      seawater and the atmosphere based on sequential vapor generation and ion molecule
      reaction mass spectrometry.
AB  - To monitor the fluctuations of dimethyl sulfur compounds at the
      seawater/atmosphere interface, an automated system was developed based on
      sequential injection analysis coupled with vapor generation-ion molecule reaction
      mass spectrometry (SIA-VG-IMRMS). Using this analytical system, dissolved
      dimethyl sulfide (DMS(aq)) and dimethylsulfoniopropionate (DMSP), a precursor to
      DMS in seawater, were monitored together sequentially with atmospheric dimethyl
      sulfide (DMS(g)). A shift from the equilibrium point between DMS(aq) and DMS(g)
      results in the emission of DMS to the atmosphere. Atmospheric DMS emitted from
      seawater plays an important role as a source of cloud condensation nuclei, which
      influences the oceanic climate. Water samples were taken periodically and
      dissolved DMS(aq) was vaporized for analysis by IMRMS. After that, DMSP was
      hydrolyzed to DMS and acrylic acid, and analyzed in the same manner as DMS(aq).
      The vaporization behavior and hydrolysis of DMSP to DMS were investigated to
      optimize these conditions. Frequent (every 30 min) determination of the three
      components, DMS(aq)/DMSP (nanomolar) and DMS(g) (ppbv), was carried out by SIA-VG
      IMRMS. Field analysis of the dimethyl sulfur compounds was undertaken at a
      coastal station, which succeeded in showing detailed variations of the compounds
      in a natural setting. Observed concentrations of the dimethyl sulfur compounds
      both in the atmosphere and seawater largely changed with time and similar
      variations were repeatedly observed over several days, suggesting diurnal
      variations in the DMS flux at the seawater/atmosphere interface.

PMID- 27046735
TI  - Update in Hospice and Palliative Care.
AB  - BACKGROUND/OBJECTIVE: The goal of this update in hospice and palliative care is
      to summarize and critique research published between January 1 and December 31,
      2014 that has a high potential for impact on clinical practice. DESIGN: To
      identify articles we hand searched 22 leading journals, the Cochrane Database of
      Systematic Reviews, and Fast Article Critical Summaries for Clinicians in
      Palliative Care. We also performed a PubMed keyword search using the terms
      "hospice" and "palliative care." MEASUREMENTS: We ranked candidate articles based
      on study quality, appeal to a breadth of palliative care clinicians, and
      potential for impact on clinical practice. RESULTS: In this manuscript we have
      summarized the findings of eight articles with the highest ratings and make
      recommendations for clinical practice based on the strength of the resulting
      evidence.

PMID- 27046736
TI  - Relevance of pituitary aromatase and estradiol on the maintenance of the
      population of prolactin-positive cells in male mice.
AB  - In previous studies we demonstrated the expression of aromatase in pituitary
      cells. This expression is gender related, and is also associated with the
      presence of prolactinomas. To ascertain the relevance of aromatase in modulating
      the populations of prolactin-positive pituitary cells an immunocytochemical and
      morphometric study of prolactin-positive pituitary cells was carried out using
      the pituitary glands of adult male and female aromatase-knockout (ArKO) mice.
      Additionally has been determined if pituitary aromatase is involved in a gender
      linked differentiated regulation of the prolactin-producing pituitary cells.
      Compared to wild-type mice, the knockout animals of both genders showed a
      significant decrease (p<0.01) in the cellular and nuclear areas of their
      prolactin cells, as well as in the percentages of the prolactin-positive cells
      and the proliferating prolactin cells. Our results suggest that estradiol is
      responsible for the maintenance of the population of prolactin cell in males and,
      so as not to disturb the endocrine reproductive environment, estradiol is
      synthesized inside the pituitary by circulating testosterone via means of
      aromatase P450, which acts in paracrine way. This new role for pituitary
      aromatase may well explain the previous findings establishing that the pituitary
      expression of aromatase is higher in males than in females, and the association
      between the development of prolactinomas and the increased expression of
      aromatase in tumours.

PMID- 27046737
TI  - Development of a community-based exercise program for people diagnosed and at
      risk for Huntington's disease: A clinical report.
AB  - BACKGROUND: Given the neurodegenerative nature of Huntington's disease (HD),
      community-based exercise programs that meet the ongoing needs of those living
      with HD are needed. The genetic nature of HD warrants the inclusion of those at
      risk for HD. The purpose of this clinical report is to describe an evidence-based
      approach to the design of a community-based exercise program to improve gait,
      balance, and fatigue for individuals diagnosed with and at-risk for HD. PROGRAM
      DESIGN: Based on the literature, clinical expertise and patient values, the
      program was designed to include four key features: (1) community-based group
      format for individuals with HD, caregivers, and those at-risk for HD; (2)
      individualized prescription within the group; (3) circuit training; and (4) use
      of outcome measures. PROGRAM IMPLEMENTATION AND OUTCOMES: The group met once
      weekly for 8 weeks for balance, strength, and cardiovascular fitness exercises.
      Three individuals participated, two diagnosed with HD and 1 considered "at-risk"
      for HD. Pre- and post- outcome measures included the 10 meter walk test, Berg
      Balance Scale, Fatigue Impact Scale, and the Timed Up and Go. Participants
      demonstrated improvement or maintenance of abilities in all measures with no
      adverse events. DISCUSSION: This clinical report describes the integration of the
      evidence, clinical expertise, and patient values to develop and implement
      individualized, community-based exercise groups, aimed to improve balance, gait
      speed, and fatigue measures for persons with HD and those at-risk. Post-program
      reflections and recommendations for those who are interested in developing
      similar programs in other communities are described.

PMID- 27046738
TI  - Exploiting Aryl Mesylates and Tosylates in Catalytic Mono-alpha-arylation of Aryl
      and Heteroarylketones.
AB  - The first general palladium catalyst for the catalytic mono-alpha-arylation of
      aryl- and heteroarylketones with aryl mesylates and tosylates is described. The
      newly developed indolyl-derived phosphine ligand L7 has been identified to
      promote this reaction efficiently. The key to success is attributed to the
      enhanced steric congestion of the catalyst and effective oxidative addition of
      the C(Ar)-OMs bond. In the presence of Pd(OAc)2 (0.25-2.5 mol %) and L7,
      selective monoarylations are achieved with ample reaction scope and product
      yields up to 95%. Importantly, we demonstrated the applicability of this protocol
      with the modification of biological phenolic compounds, rendering it amenable for
      functionalization of phenolic (pro)drugs. 

PMID- 27046739
TI  - Sonication of Abdominal Drains: Clinical Implications of Quantitative Cultures
      for the Diagnosis of Surgical Site Infection.
AB  - BACKGROUND: The use of drains in patients undergoing abdominal surgery has been a
      subject of debate for several decades. In this paper, the usefulness of
      quantitative cultures of sonicated abdominal drains for diagnosing surgical site
      of infection (SSI) and the association between culture results with patient
      outcome is evaluated. METHODS: Forty-five abdominal drainage tubes from 35
      patients who underwent abdominal surgery were studied. Samples were sonicated for
      5 min, the sonicate was centrifuged, and the sediment was cultured on different
      media. Total bacterial counts were adjusted to the actual surface of the drainage
      tubing. Clinical information of the patients was reviewed retrospectively.
      RESULTS: A relation was observed between SSI and the use of drains for more than
      3 d (p = 0.0216). The presence of a suspected pathogen was related to the
      prevalence of SSI (p = 0.035), complications (p = 0.013), and greater leukocyte
      count (p = 0.048 Mann Whitney test), as well as to the use of drains for more
      than 3 d (p = 0.0386) and to the serous appearance of the exudates at the point
      of insertion of the drain (p = 0.0399). The sonication procedure showed a
      sensitivity of 50%, specificity of 84.2%, positive predictive value of 72.72%,
      and negative predictive value of 66.67% in the diagnosis of SSI. The most
      commonly isolated group of organisms was coagulase-negative staphylococci, being
      present in 18 patients (51.43%) who, however, were not associated with SSI. One
      or two organisms considered as pathogens were detected in 11 patients (31.43%).
      The more common pathogens detected were Enterobacteriae spp. (nine patients):
      Enterobacter aerogenes (2), Enterobacter cloacae (1), Escherichia coli (4),
      Klebsiella pneumoniae (1), Morganella morganii (1); and Pseudomonas aeruginosa
      (five patients). Candida spp. and Enterococcus spp. were detected in one patient
      each one. CONCLUSIONS: The detection and quantification of organisms not present
      in skin microbiota after drain sonication is helpful in the diagnosis of SSI and
      it is associated with a worse outcome in patients. Duration of use of drainage
      tubes is an independent risk factor for the development of SSI.

PMID- 27046740
TI  - Education and Role Title as Predictors of Enacted (Actual) Scope of Practice in
      Generalist Nurses in a Pediatric Academic Health Sciences Center.
AB  - OBJECTIVE: The aim of this study is to document the enacted (actual) scope of
      practice (SOP) of nurses in pediatric settings in relation to education level and
      position. BACKGROUND: Baccalaureate-prepared staff nurses routinely carry out
      only a fraction of the activities essential for quality of care and patient
      safety they have been educated for. A direct care nurse clinician role exists for
      nurses with bachelor's degrees in Quebec, Canada. METHOD: Survey of 301 nurses in
      a pediatric university hospital in Quebec was conducted. RESULTS: Enacted
      (actual) SOP for baccalaureate-educated nurses was significantly broader than
      that of nurses with junior college diplomas and nurse clinicians (baccalaureate
      educated) carried out complex activities more frequently. CONCLUSION: The
      creation of job titling and role descriptions that reflect the upper range of
      nursing competencies could be an important tool for promoting broadened SOP for
      baccalaureate nurses.

PMID- 27046741
TI  - Nursing Administration Research Priorities: Findings From a Delphi Study.
AB  - OBJECTIVE: The aim of this study is to determine the priorities for nursing
      administration research (NAR) in the United States. BACKGROUND: Previously known
      as the Council of Graduate Educators in Administrative Nursing, CGEAN provides an
      avenue for researchers and educators focused on NAR to partner, dialogue, obtain
      funding resources, and present their findings at a biennial International Nursing
      Administration Research Conference (INARC). In late 2013, with a goal of building
      consensus, CGEAN convened an INARC postconference to initiate the process of
      establishing critical NAR priorities for the future. METHODS: Data from a 3
      staged Delphi study were used to identify relevant research topics and determine
      administrative research priorities. RESULTS: Eight final categories of NAR were
      determined. CONCLUSIONS: This study found economic valuing of nursing and
      designing effective future healthcare delivery systems to be high priorities for
      NAR.

PMID- 27046742
TI  - The Impact of Shared Governance Over Time in a Small Community Hospital.
AB  - OBJECTIVE: This study examined the impact of shared governance (SG) on the
      professional nursing practice environment of a small community hospital over
      time. BACKGROUND: Shared governance has been shown to empower nurses in direct
      patient care to make decisions about their practice and improve job satisfaction.
      No research has been found that examined the progression of SG over time in a
      small community hospital. METHODS: Questionnaires pertaining to the professional
      practice environment, perception of nursing leadership, nurse empowerment, nurse
      satisfaction, risk of practice errors, and comfort with evidence-based practice
      were administered to all nurses employed at a 149-bed community hospital in
      central North Carolina for 5 consecutive years. RESULTS: Results showed that
      nursing leadership and SG explained 90% of the variance in the nursing
      professional practice environment. This relationship held true for 5 years. All
      variables showed continued improvement for 4 years, until year 5 when the
      organization experienced disruptive change. Even during this year, the results
      did not return to baseline. CONCLUSIONS: In order to improve the professional
      practice environment of nurses, hospitals should focus on strong nursing
      leadership and a sound SG infrastructure.

PMID- 27046743
TI  - Hypertension in dichorionic twin gestations: how is birthweight affected?
AB  - OBJECTIVE: To examine the association between hypertension (HTN) and discordant
      or small for gestational age (SGA) birthweights among dichorionic twin
      pregnancies. METHODS: Retrospective cohort of dichorionic twin pregnancies
      delivered at >=24 0/7 weeks from 2002 to 2015. Women with HTN in pregnancy
      (gestational HTN or preeclampsia) and chronic HTN (cHTN) were compared to those
      with uncomplicated dichorionic pregnancies. Outcomes were any discordance (>=20%
      difference within each twin pair), discordance with at least one twin also SGA
      (>=20% discordance with at least one twin also SGA <10th percentile), and SGA
      alone of one or both twins (<5th and <10th percentile). RESULTS: 474 Dichorionic
      pregnancies were identified. Women with HTN in pregnancy had an adjusted odds
      ratio (aOR) of 2.68 (95% CI 1.48-4.87) for any discordance and 2.94 (1.57-5.48)
      for discordance with at least one twin also SGA. These aORs for women with cHTN
      were 4.65 (1.39-15.52) and 4.37 (1.21-15.76), respectively. Significant
      differences were not observed for SGA alone of one or both twins. CONCLUSION:
      Among dichorionic pregnancies, both women with HTN in pregnancy and cHTN
      demonstrated increased odds of any discordant growth, as well as discordance with
      concurrent SGA of at least one twin. Odds of these outcomes were greatest with
      cHTN.

PMID- 27046744
TI  - Long-term use of a new topical formulation containing piroxicam 0.8% and
      sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept
      study.
AB  - INTRODUCTION: Cyclooxygenase (COX) 1 and 2 enzyme up-regulation is involved in
      the pathogenetic process of actinic keratosis (A.K.) and non-melanoma skin
      cancers. Diclofenac, a non-steroidal anti-inflammatory (N.S.A.I.D.) drug, is used
      as topical treatment of A.K. Piroxicam is a N.S.A.I.D. characterized by a high
      COX-1 inhibition activity. STUDY AIM: We conducted an 18 month exploratory open
      label study on A.K., to assess the efficacy and tolerability of a new topical
      formulation of piroxicam and sunscreen in A.K. PATIENTS: Enrolled subjects
      applied a galenic formulation of piroxicam 0.8%, vehiculated in a topical product
      containing sun filters with high (50+) and broad spectrum (UVA) actions, twice a
      day for 6 months. Subjects were then followed up for additional 12 months. Thirty
      eight subjects with a total of 69 A.K. lesions participated in the trial. The
      primary outcome was the evolution of the Actinic Keratosis Erythema Scale Atrophy
      (A.K.E.S.A) score assessing erythema, scale, and atrophy of a target A.K. lesion.
      Secondary outcomes were the percentage of treated lesions with complete (100%) or
      partial (>=75%) clearance and the evaluation skin tolerability. RESULTS:
      A.K.E.S.A. mean (S.D.) score at baseline was 7.5 (1.2). After 6 months of
      treatment, A.K.E.S.A. score decreased to 0.9 (1.1), a -88% reduction versus
      baseline. At the end of follow-up, A.K.E.S.A. score was 0.8 (1.2). A complete
      response was achieved in 38 of the 69 lesions (55%, 95% C.I.: 43% to 66%) and
      clearance was maintained 1 year post-treatment. A partial clearance was observed
      in 57 of 69 treated lesions (83%, 95% C.I.: 73% to 91%). Adverse events were
      limited to mild local irritation. CONCLUSION: Our experience suggests that 6
      month topical piroxicam 0.8% is efficacious and well tolerated in A.K. Clinical
      efficacy is maintained 1 year post-treatment. The main limitation of our study is
      that it was an open label non-controlled trial. Future controlled trials are
      warranted in order to compare the efficacy and tolerability of this topical
      piroxicam preparation with standard treatments in the management of A.K.

PMID- 27046745
TI  - Gender difference in mobile phone use and the impact of digital device exposure
      on neck posture.
AB  - This cross-sectional study aimed to identify gender differences in the cervical
      postures when young adults were using mobile phones, as well as the correlations
      between the postures and the digital devices use (computer and mobile phone).
      Questionnaires regarding the habits of computer and mobile phone use were
      administrated to 429 subjects aged from 17 to 33 years old (19.75 +/- 2.58 years
      old). Subjects were instructed to stand habitually and use a mobile phone as in
      daily life; the sagittal head and cervical postures were measured by head
      flexion, neck flexion angle and gaze angle. Male participants had a significantly
      larger head flexion angle (96.41 degrees  +/- 12.23 degrees  vs. 93.57 degrees 
      +/- 12.62 degrees , p  =  0.018) and neck flexion angle (51.92 degrees   +/- 
      9.55 degrees  vs. 47.09 degrees  +/- 9.45 degrees , p  <  0.001) than females.
      There were significant differences in head (F  =  3.62, p  =  0.014) and neck
      flexion (F  =  3.99, p  =  0.009) between different amounts of computer use.
      Practitioner Summary: We investigated possible gender differences in head and
      neck postures of young adults using mobile phones, as well as the potential
      correlations between these postures and digital device use. We found that males
      displayed larger head and neck flexion angles than females, which were associated
      with the amount of computer use.

PMID- 27046747
TI  - How Technology Can Impact Surgeon Performance: A Randomized Trial Comparing 3
      Dimensional versus 2-Dimensional Laparoscopy in Gynecology Oncology.
AB  - This randomized clinical trial (Canadian Task Force classification I) aimed to
      compare 2-dimension (2-D) versus 3-dimensional (3-D) laparoscopic hysterectomy
      and pelvic lymphadenectomy in endometrial and cervical cancer patients. Between
      December 2014 and March 2015, 90 patients were enrolled: 29 (32.2%) with early or
      locally advanced cervical cancer after neoadjuvant treatment and 61 (67.8%) with
      early-stage endometrial cancer. Patients were randomly assigned to undergo 2-D
      (Group A, n = 48 [53.3%]) or 3-D (Group B, n = 42 [46.7%)]) laparoscopy. Baseline
      characteristics were superimposable in the 2 groups. Median operative time was
      similar in the 2 groups. Median estimated blood loss during lymphadenectomy was
      significantly lower in Group B than in Group A (38 mL [range, 0-450] vs 65 mL
      [range, 0-200]; p = .033). In cervical cancer patients operative time of pelvic
      lymphadenectomy performed by "novice" surgeons (those with <10 procedures
      performed) was statistically significantly lower in Group B (p = .047). No
      differences in perioperative outcomes and postoperative complications were
      observed between the 2 groups. The 2-D and 3-D systems can be used safely in
      laparoscopic hysterectomy. However, the 3-D system could provide key benefits to
      intraoperative techniques and postoperative outcomes in reducing operative time
      for "expert" surgeons and in enhancing surgical precision for "novice" surgeons.

PMID- 27046748
TI  - Ovalbumin-induced allergic inflammation lead to structural alterations in mouse
      model and protective effects of intranasal curcumin: A comparative study.
AB  - BACKGROUND: Antigen exposure and persistent inflammation leads to structural
      changes in the asthmatic airways which are collectively termed as "airway
      remodelling". Presently available asthma medications ameliorate inflammations but
      are unable to prevent or reverse the airway remodelling process as most of the
      treatment strategies are only focused on inflammation instead of remodelling.
      METHODS: Curcumin, a phytochemical present in the rhizome of Curcuma longa is
      well known for its anti-inflammatory activity; however, the main drawback is its
      poor bioavailability which limits its therapeutic approval. So, the effect of
      nasal curcumin on acute and chronic asthma has been studied where short exposure
      to ovalbumin (4 days) represents acute phase whereas repeated exposures for
      longer (twice per week till 5 weeks) represents chronic asthma. Disodium
      cromoglycate (DSCG, 50mg/kg, i.p.) and dexamethasone (1mg/kg, i.p.) were used as
      standard drugs in acute and chronic model of asthma respectively. RESULTS: OVA
      induced airway inflammation initiated in acute stage led to remodelling due to
      persistent inflammation, epithelial and sub epithelial thickening (smooth muscle
      thickening), extracellular matrix (ECM) deposition, goblet cell hyperplasia and
      mucus plug formation. Intranasal curcumin is effective in inhibiting airway
      inflammation and remodelling both by maintaining the structural integrity of
      lungs in terms of inflammation, airway wall thickening and mucus production.
      CONCLUSION: Our findings suggest that curcumin administered through nasal route
      might prove therapeutically efficient in inhibiting allergic airway inflammations
      and maintaining structural integrity in the mouse model of allergic asthma. This
      may lead to the development of curcumin aerosol in near future.

PMID- 27046749
TI  - [Not Available].

PMID- 27046750
TI  - [Not Available].
AB  - Allergic rhinitis is the most common form of allergy with a prevalence of 30%.
      Allergic rhinitis is associated with substantial health economic costs and
      patient suffering. Asthma is strongly associated with allergic rhinitis. The
      treatment of allergic rhinitis should be individualized and include the whole
      airway. The treatment goals should be a patient free of symptoms affecting their
      daily life or sleep. 

PMID- 27046751
TI  - [Not Available].
AB  - Anaphylaxis is an acute, severe, systemic hypersensitivity reaction and is
      potentially fatal. It is sudden and almost always unanticipated, and it involves
      more than one organ system. Symptom onset varies widely from within seconds to a
      few hours, but usually occurs within 30 minutes of exposure to the trigger. Early
      diagnosis and prompt initiation of treatment is important and the diagnosis
      should be established only when the diagnostic criteria are met. Any delay in the
      recognition of the initial signs and symptoms can result in a fatal outcome,
      either because of airway obstruction or circulatory collapse. Adrenaline is the
      drug of choice and should be immediately administered intramuscularly with
      suspected reaction. 

PMID- 27046752
TI  - [Not Available].
AB  - Acute allergic reactions to food are often IgE mediated. Symptoms vary in
      severity; from mild oral itching to anaphylactic reactions. Where birch pollen
      allergy is endemic, mild allergic reactions from e.g. fresh fruits and nuts are
      most likely caused by cross reactivity between pollen and plants (cross
      reactions). These mild symptoms, if caused by cross reactivity, do not progress
      to more severe symptoms, in contrast to "true" food allergy. However, making this
      distinction is a delicate task, since more severe reactions also often start with
      mild oral symptoms. Also conventional allergy tests, such as skin-prick test and
      blood test to detect IgE-antibodies (IgE-ab) to foods, discriminate poorly
      between cross reactions and true allergy. Component resolved diagnostics, i.e.
      analysis of IgE-ab to specific proteins in an allergen and CD-sens (Basophil
      allergen threshold sensitivity), can differentiate pollen-related cross reactions
      from true allergic reactions that may cause anaphylaxis. There is no widely
      accepted or evidence based treatment for food allergy, but reports from several
      studies have been published and many are in progress, where oral immunotherapy
      probably is the most promising form of treatment. 

PMID- 27046753
TI  - [Not Available].

PMID- 27046754
TI  - [Not Available].

PMID- 27046755
TI  - [Not Available].
AB  - Allergic sensitization, an important risk factor for allergic diseases such as
      asthma and rhinitis, has increased worldwide. Almost half of the young adult
      population is sensitized to common airborne allergens. Parallel, the prevalence
      of asthma and clinical allergy also increased all over the world. Allergic
      diseases are the most common diseases among children, adolescents and young
      adults in Sweden. Among adults, 8-10% have asthma, 30% rhinitis and 11% eczema.
      Among children and adolescents around 5-8% report food allergy. Part of the
      increase in asthma prevalence is related to changes in diagnostic criteria and
      increased awareness in the population. The increase may have levelled off in some
      areas. 

PMID- 27046756
TI  - [Not Available].

PMID- 27046757
TI  - [Not Available].
AB  - Allergen immunotherapy (AIT) to patients with allergy towards pollens, cats or
      house dust mite provides longstanding improvement of symptoms of
      rhinoconjunctivitis and allergic asthma and reduces the need for symptomatic
      medication. In addition, some studies suggest that AIT can protect from the
      development of asthma in children with allergic rhinitis. The clinical effects of
      AIT are explained by a shift from a Th2 to a Th1-mediated immune response upon
      allergen exposure. In Sweden the treatment is given as sublingual tablets (grass)
      or subcutaneous injections, and a treatment period of 3-4 years is necessary to
      ensure longstanding effect of the treatment. Serious side-effects such as asthma
      attacks or anaphylaxis are uncommon, if the treatment is provided by staff
      specifically trained to administer AIT. Intralymphatic administration of the
      allergen extract is a novel and promising approach that might shorten the
      treatment period with similar clinical effects. 

PMID- 27046758
TI  - [Not Available].
AB  - Asthma, eczema, food allergy and allergic rhinitis are common and the cause is
      still largely unknown, but it is the subject of extensive research. The research
      results are inconclusive, probably due to individual differences in vulnerability
      to different exposures and to a highly multifactorial origin. Several
      environmental factors have been identified as risk factors or as having a
      potentially protective effect. Smoking during pregnancy or childhood increases
      the risk of obstructive symptoms and asthma. Breastfeeding reduces the risk of
      infectious diseases and thereby also the risk of early obstructive symptoms. Even
      if mothers avoid certain foods during pregnancy or breastfeeding, this does not
      reduce the risk of allergic disease in the child. The child should be introduced
      to foods between four and six months of age, without avoiding or delaying any
      particular food. Vaccinations do not affect the risk of allergic disease. The
      risk of allergic disease is not increased by exposure to furry animals in the
      home, if the child is healthy. However, children who are already allergic should
      at least avoid the animals to which they are allergic. 

PMID- 27046759
TI  - [Healthy people's reluctance to take medication is underestimated. Study shows
      that healthy people's attitude to cardiovascular primary prevention is complex].
AB  - Physicians often assume that patients have a negligible aversion to lifelong
      medication and that medication disutility is almost zero.  While a large number
      of patients are willing to take a lifelong primary prevention therapy that allow
      them to live longer, there is a group with extreme medication disutility desiring
      10 years or more in life expectancy in order to consider therapy. Also, the
      expected benefits of medication often exceed the real benefits. When initiating
      medication the patients should be actively involved in the decision-making
      process. An individualized approach could potentially increase the adherence to
      therapy.

PMID- 27046760
TI  - [Not Available].

PMID- 27046761
TI  - [Not Available].

PMID- 27046762
TI  - [Not Available].

PMID- 27046763
TI  - [Not Available].

PMID- 27046764
TI  - [Not Available].

PMID- 27046765
TI  - [Not Available].

PMID- 27046766
TI  - [Not Available].

PMID- 27046767
TI  - [Not Available].

PMID- 27046768
TI  - [Not Available].

PMID- 27046769
TI  - [Not Available].

PMID- 27046770
TI  - The self-report Dissociative Disorders Interview Schedule: A preliminary report.
AB  - A self-report version of the Dissociative Disorders Interview Schedule (SR-DDIS)
      was administered to 100 inpatients in a hospital-based trauma program. All
      participants had previously completed the interviewer-administered version of the
      DDIS. When we compared the overall results on the DDIS and SR-DDIS for the 100
      inpatients, the findings were very consistent for both symptom clusters and
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),
      diagnoses. The agreement rate between the 2 versions for DSM-5 diagnoses was fair
      to substantial using Cohen's kappa, with agreement being substantial for 4 out of
      the 7 diagnoses made by the DDIS. It appears likely that the SR-DDIS can be used
      instead of the DDIS, at least in clinical populations, with no clinically or
      conceptually significant differences between the results obtained with the 2
      versions.

PMID- 27046771
TI  - Controlling the Adhesion of Superhydrophobic Surfaces Using Electrolyte Jet
      Machining Techniques.
AB  - Patterns with controllable adhesion on superhydrophobic areas have various
      biomedical and chemical applications. Electrolyte jet machining technique (EJM),
      an electrochemical machining method, was firstly exploited in constructing
      dimples with various profiles on the superhydrophobic Al alloy surface using
      different processing parameters. Sliding angles of water droplets on those
      dimples firstly increased and then stabilized at a certain value with the
      increase of the processing time or the applied voltages of the EJM, indicating
      that surfaces with different adhesion force could be obtained by regulating the
      processing parameters. The contact angle hysteresis and the adhesion force that
      restricts the droplet from sliding off were investigated through experiments. The
      results show that the adhesion force could be well described using the classical
      Furmidge equation. On account of this controllable adhesion force, water droplets
      could either be firmly pinned to the surface, forming various patterns or slide
      off at designed tilting angles at specified positions on a superhydrophobic
      surface. Such dimples on superhydrophopbic surfaces can be applied in water
      harvesting, biochemical analysis and lab-on-chip devices. 

PMID- 27046772
TI  - Multi-hollow polymer microspheres with enclosed surfaces and compartmentalized
      voids prepared by seeded swelling polymerization method.
AB  - Multi-hollow particles have drawn extensive research interest due to their high
      specific areas and abundant inner voids, whereas their convenient synthesis still
      remains challenging. In this paper, we report a simple and convenient method
      based on seeded swelling polymerization to prepare the multi-hollow microspheres
      with enclosed surfaces and compartmentalized voids using monodisperse poly
      (styrene-co-sodium 4-vinylbenzenesulfonate) microspheres as seed particles. A
      formation mechanism of the multi-hollow structure was proposed involving the
      processes of water absorption, coalescence and stabilization of water domains,
      immobilization of multi-hollow structure, and coverage of surface dimples. The
      influencing parameters on the morphology of the microspheres, including weight
      ratio of sodium 4-vinylbenzenesulfonate to styrene in the seed particles, dosage
      of the swelling monomer and the crosslinking agent were systematically
      investigated. The internal structure of the resultant microspheres could be tuned
      from solid to multi-hollow by controlling over these parameters. Multi-hollow
      microspheres with compartmentalized chambers, smooth surfaces and narrow size
      distributions were obtained as a result. 

PMID- 27046773
TI  - Quantum Mechanical and Molecular Dynamics Studies of the Reaction Mechanism of
      the Nucleophilic Substitution at the Si Atom.
AB  - The mechanism of the nucleophilic substitution at the Si atom, SiH3Cl + Cl*(-) ->
      SiH3Cl* + Cl(-), is examined by both quantum mechanical (QM) and molecular
      dynamics (MD) methods. This reaction proceeds by two steps with the inversion or
      retention of the configuration passing through an intermediate with the trigonal
      bipyramid (TBP) structure, although the conventional SN2 reaction at the C atom
      proceeds by one step with the inversion of the configuration passing through a
      transition state with the TBP structure. We followed by the QM calculations all
      the possible paths of the substitution reaction that undergo the TBP
      intermediates with the cis and trans forms produced by the frontside and backside
      attacks of Cl(-). As a result, it was thought that TBPcis1 produced with a high
      probability is readily transformed to the energetically more stable TBPtrans.
      This fact was also shown by the MD simulations. In order to obtain more
      information concerning the trajectory of Cl(-) on the dissociation from TBPtrans,
      which we cannot clarify on the basis of the energy profile determined by the QM
      method, the MD simulations with and without the water solvent were conducted and
      analyzed in detail. The QM-MD simulations without the water solvent revealed that
      the dissociation of Cl(-) from TBPtrans occurs without passing through TBPcis1'.
      The ONIOM-MD simulations with the water solvent further suggested that the
      thermal fluctuation of the water solvent significantly affects the oscillation of
      the kinetic and potential energies of the substrate to facilitate the
      isomerization of the TBP intermediate from the cis form to the trans form and the
      subsequent dissociation of Cl(-) from TBPtrans.

PMID- 27046774
TI  - April Showers Bring May Flowers.

PMID- 27046775
TI  - What Price Certainty?

PMID- 27046776
TI  - Re: "Insignificant Findings: Don't Leave Them Questioning the Significance".

PMID- 27046777
TI  - Versatile Fabrication of Self-Aligned Nanoscale Hall Devices Using Nanowire
      Masks.
AB  - In this work, we present an ingenious method to fabricate self-aligned nanoscale
      Hall devices using chemically synthesized nanowires as both etching and
      deposition masks. This versatile method can be extensively used to make
      nanoribbons out of arbitrary thin films without the need for extremely high
      alignment accuracy to define the metal contacts. The fabricated nanoribbon width
      scales with the mask nanowire width (diameter), and it can be easily reduced down
      to tens of nanometers. The self-aligned metal contacts from the sidewall extend
      to the top surface of the nanoribbon, and the overlap can be controlled by tuning
      the deposition recipe. To demonstrate the feasibility, we have fabricated
      Ta/CoFeB/MgO nanoribbons sputtered on a SiO2/Si substrate with different metal
      contacts, using synthesized SnO2 nanowires as masks. Anomalous Hall effect
      measurements have been carried out on the fabricated nanoscale Hall device in
      order to study the current-induced magnetization switching in the nanoscale heavy
      metal/ferromagnet heterostructure, which has shown distinct switching behaviors
      from micron-scale devices. The developed method provides a useful fabrication
      platform to probe the charge and spin transport in the nanoscale regime.

PMID- 27046778
TI  - Wind turbines and idiopathic symptoms: The confounding effect of concurrent
      environmental exposures.
AB  - Whether or not wind turbines pose a risk to human health is a matter of heated
      debate. Personal reactions to other environmental exposures occurring in the same
      settings as wind turbines may be responsible of the reported symptoms. However,
      these have not been accounted for in previous studies. We investigated whether
      there is an association between residential proximity to wind turbines and
      idiopathic symptoms, after controlling for personal reactions to other
      environmental co-exposures. We assessed wind turbine exposures in 454 residences
      as the distance to the closest wind turbine (Dw) and number of wind turbines
      <1000m (Nw1000). Information on symptoms, demographics and personal reactions to
      exposures was obtained by a blind questionnaire. We identified confounders using
      confounders' selection criteria and used adjusted logistic regression models to
      estimate associations. When controlling only for socio-demographic
      characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38,
      95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and
      Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and
      "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal
      reactions to noise from sources different from wind turbines and agricultural
      odor exposure, we did not observe a significant relationship between residential
      proximity to wind turbines and symptoms and the parameter estimates were
      attenuated toward zero. Wind turbines-health associations can be confounded by
      personal reactions to other environmental co-exposures. Isolated associations
      reported in the literature may be due to confounding bias.

PMID- 27046780
TI  - Sterilization and Reprocessing: Overcoming Challenges, Safeguarding Patients.

PMID- 27046779
TI  - Racemicystis crocea gen. nov., sp. nov., a soil myxobacterium in the family
      Polyangiaceae.
AB  - A novel bacterial strain designated MSr9521T was isolated in 2014 from a soil
      sample collected in 1986 from the Philippines. The novel bacterium shows
      myxobacterial characteristics that include pseudoplasmodial swarming, fruiting
      body formation and predatory ability to lyse microorganisms. The strain is
      chemoheterotrophic, mesophilic and aerobic. Major fatty acids are C18:1, C17:1 2
      OH and iso-C15:0, and also contains trace amounts of omega-3/-6 polyunsaturated
      fatty acids. The G+C content of the genomic DNA is 70.4 mol%. The 16S rRNA gene
      sequence shows 95-96 % closest similarity to Sorangium cellulosum DSM 14627T,
      Polyangium fumosum Pl fu5T, Jahnella thaxteri Pl t4T and Byssovorax cruenta By
      c2T. The molecular phylogenetic analysis shows that the novel isolate forms a
      novel branch in the family Polyangiaceae, suborder Sorangiineae. Polyphasic
      taxonomic characterization suggests that the strain MSr9521T represents a novel
      species of a new genus in the family Polyangiaceae, for which the name
      Racemicystis crocea gen. nov., sp. nov. is proposed. The type strain of
      Racemicystis crocea is MSr9521T (=DSM 100773T=NCCB 100574T). 

PMID- 27046781
TI  - Rising Stars among AAMI's Sterilization Standards.

PMID- 27046782
TI  - A Roundtable Discussion: Safer Sterilization and Reprocessing Require Systemwide
      Improvements.

PMID- 27046783
TI  - Safe to Handle? Comparing Manually and Machine-Washed Medical Devices.

PMID- 27046784
TI  - ST91: A Roadmap for Reprocessing Flexible and Semirigid Endoscopes.

PMID- 27046785
TI  - Bringing Order to Sterile Processing through Standardized Processes.

PMID- 27046786
TI  - Lessons Learned from FDA's Regulation of 'Single-Use' Device Reprocessing.

PMID- 27046787
TI  - Barriers to Adopting FDA Guidance in Central Sterile Departments.

PMID- 27046789
TI  - Long-term performance and microbial community characterization of an osmotic
      anammox system for removing reverse-fluxed ammonium.
AB  - A novel osmotic anammox (OsAMX) system coupling nitritation-anammox with forward
      osmosis (FO) has been developed for removal of reverse-fluxed ammonium when using
      NH4HCO3 as a draw solute. In this study, long-term performance and microbial
      community structure were investigated. The nitritation-anammox reactor maintained
      an ammonium concentration of 7.0+/-5.0mgNL(-1) (DO=0.9+/-0.2mgO2L(-1)), while the
      FO achieved a water flux of 2.3+/-0.4LMH (0.5M NH4HCO3 draw). The low water flux
      was obtained likely due to concentration polarization, reverse salt flux (RSF)
      and membrane fouling. Sequencing analyses reveled that Candidatus Jettenia was
      the dominant anammox genus, while Candidatus Brocadia was most abundant in
      biofilm. The shift of anammox bacterial population indicated possible higher
      tolerance of Ca. Brocadia for DO or elevated RSF. These results encourage further
      investigation of OsAMX system optimization, membrane fouling migration
      strategies, and application with actual wastewater. 

PMID- 27046790
TI  - Chemical composition of essential oils of Anthemis secundiramea Biv. subsp.
      secundiramea (Asteraceae) collected wild in Sicily and their activity on micro
      organisms affecting historical art craft.
AB  - In the present study, the chemical composition of the essential oil from the
      aerial parts of Anthemis secundiramea Biv. subsp. secundiramea L. collected in
      Sicily was evaluated by GC and gas chromatography-mass spectrometry. The main
      components of A. secundiramea were (Z)-lyratyl acetate (14.6%), (Z)-chrysanthenyl
      acetate (9.9%), (Z)-chrysanthenol (8.7%) and (E)-chrysanthenyl acetate (7.7%).
      The comparing with other studied oils of genus Anthemis belonging to the same
      clade is discussed. Antibacterial and antifungal activities against some micro
      organisms infesting historical art craft, were also determined.

PMID- 27046791
TI  - Genomic and proteomic analysis of the inhibition of synthesis and secretion of
      aldosterone hormone induced by quinocetone in NCI-H295R cells.
AB  - Quinoxaline 1,4-dioxides (QdNOs) are widely used as a kind of antibacterial
      growth promoter in animal husbandry. The adrenal cortex was found to be one of
      the main toxic targets of QdNOs, accompanied by a decreased aldosterone level.
      However, the way in which QdNOs decrease production of the hormone aldosterone is
      far from clear. To illustrate the mechanism by which QdNOs damage the adrenal
      cortex and decrease aldosterone hormone levels, the QdNOs were screened to choose
      the drug with most toxic effects on aldosterone production, and then to reveal
      the mechanism between the gene and protein profiles in human adrenocortical cells
      (NCI-H295R cells). The results found that quinocetone (QCT) showed the highest
      adrenal toxic effect among QdNOs. After exposing H295R cells to 10 and 20MUM QCT
      for 24h, compared with blank cells, the gene and protein expression profiles
      obtained were analyzed by microarray and MALDI TOF/TOF mass spectrometry,
      respectively. The results of microarray analysis suggested that ABCG1 and SREBF1,
      which were involved in the cholesterol biosynthetic and metabolic processes, and
      CYP17A1, NR4A2 and G6PD, which were related to aldosterone biosynthesis, were
      important molecular targets. It has been speculated that PKC and ERK pathways
      might be involved in the reduction of aldosterone production caused by QCT,
      through enhanced mRNA expression of CYP17A1. Additionally, JNK and p38MAPK signal
      transduction pathways might participate in apoptosis induced by QCT. Twenty-nine
      and 32 protein spots were successfully identified when cells were treated with 10
      and 20MUM QCT, respectively. These identified proteins mainly included material
      synthesis and energy metabolism-related proteins, transcription/translation
      processing-related proteins, signal transduction proteins, cytoskeletal proteins,
      molecular chaperones, proteins related to response to stress, and transport
      proteins. Further investigations suggested that oxidative stress caused by QCT
      was exacerbated through disruption of the Keap1/Nrf2/ARE anti-oxidative stress
      pathway. Taken together, the data demonstrated for the first time that the
      Keap1/Nrf2/ARE pathway plays a crucial role in adrenal toxicity, and that CYP17A1
      was the key switch to reduce the aldosterone production induced by QCT.
      Furthermore, large numbers of genes and proteins and entry points for research in
      the inhibition of aldosterone synthesis induced by QCT were offered, which will
      provide new insight into the adrenal toxicity of QdNOs and help to provide a
      theoretical foundation for the formulation of safety controls for products
      obtained from animals and to design new QdNOs with less harmful effects.

PMID- 27046792
TI  - Characterization of cytoprotective and toxic properties of iron chelator SIH,
      prochelator BSIH and their degradation products.
AB  - Free cellular iron catalyzes the formation of toxic hydroxyl radicals and
      therefore chelation of iron could be a promising therapeutic approach in
      pathological states associated with oxidative stress. Salicylaldehyde
      isonicotinoyl hydrazone (SIH) is a strong intracellular iron chelator with well
      documented potential to protect against oxidative damage both in vitro and in
      vivo. Due to the short biological half-life of SIH and risk of toxicity due to
      iron depletion, boronate prochelator BSIH has been designed. BSIH cannot bind
      iron until it is activated by certain reactive oxygen species to active chelator
      SIH. The aim of this study was to examine the toxicity and cytoprotective
      potential of BSIH, SIH, and their decomposition products against hydrogen
      peroxide-induced injury of H9c2 cardiomyoblast cells. Using HPLC, we observed
      that salicylaldehyde was the main decomposition products of SIH and BSIH,
      although a small amount of salicylic acid was also detected. In the case of BSIH,
      the concentration of formed salicylaldehyde consistently exceeded that of SIH.
      Isoniazid and salicylic acid were not toxic nor did they provide any antioxidant
      protective effect in H9c2 cells. In contrast, salicylaldehyde was able to chelate
      intracellular iron and significantly preserve cellular viability and
      mitochondrial inner membrane potential induced by hydrogen peroxide. However it
      was consistently less effective than SIH. The inherent toxicities of
      salicylaldehyde and SIH were similar. Hence, although SIH - the active chelating
      agent formed following the BSIH activation - undergoes rapid hydrolysis, its
      principal decomposition product salicylaldehyde accounts markedly for both
      cytoprotective and toxic properties.

PMID- 27046793
TI  - Nanoparticle assembly: from fundamentals to applications: concluding remarks.
AB  - Nanoparticles, due to their broadly tunable functions, are major building blocks
      for generating new materials. However, building such materials for practical
      applications by self-assembly is quite challenging. Following the Faraday
      Discussion on "Nanoparticle Assembly: from Fundamentals to Applications" we
      discuss here the current trends in the field of self-assembly, including:
      understanding the unique interplay of molecular and nanoscale effects, a
      development of novel approaches for the creation of targeted nanoparticle
      architectures, advances in controlling dynamic behavior of systems and enabling
      new functions through specifically formed structures. 

PMID- 27046794
TI  - Preoperative computed tomography scan to predict pancreatic fistula after distal
      pancreatectomy using gland and tumor characteristics.
AB  - BACKGROUND: Preoperative risk stratification for postoperative pancreatic fistula
      in patients undergoing distal pancreatectomy is needed. METHODS: Risk factors for
      postoperative pancreatic fistula in 220 consecutive patients undergoing distal
      pancreatectomy at 2 major institutions were recorded retrospectively. Gland
      density was measured on noncontrast computed tomography scans (n = 101), and
      histologic scoring of fat infiltration and fibrosis was performed by a
      pathologist (n = 120). RESULTS: Forty-two patients (21%) developed a clinically
      significant pancreatic fistula within 90 days of surgery. Fat infiltration was
      significantly associated with gland density (P = .0013), but density did not
      predict pancreatic fistula (P = .5). Recursive partitioning resulted in a
      decision tree that predicted fistula in this cohort with a misclassification rate
      less than 15% using gland fibrosis (histology), density (HU), margin thickness
      (cm), and pathologic diagnosis. CONCLUSIONS: This multicenter study shows that no
      single perioperative factor reliably predicts postoperative pancreatic fistula
      after distal pancreatectomy. A decision tree was constructed for risk
      stratification.

PMID- 27046795
TI  - Stoma creation: does onset of ostomy care education delay hospital length of
      stay?
AB  - BACKGROUND: Balancing patient safety with hospital length of stay (LOS) and
      associated cost is critically important. Subjectively, we have observed that
      patients undergoing ostomy creation early in the week have a shorter LOS.
      METHODS: We retrospectively reviewed LOS based on day of the week the operation
      was performed. RESULTS: We reviewed 180 patients undergoing minimally invasive
      surgery with planned ostomy. Group 1 underwent surgery on Monday to Wednesday (n
      = 77), Group 2 on Thursday (n = 49), and Group 3 on Friday (n = 54). The average
      LOS for Group 1, 2, and 3 was 6.2, 4.9, and 7.2 days, respectively. The average
      number of visits with ostomy nursing for Group 1, 2, and 3 was 2.7, 1.8, and 2.3,
      respectively. Day of initial ostomy nursing visit was significantly correlated
      between the delay to initial visit and LOS with Group 3 delayed most.
      CONCLUSIONS: Patients with the longest delay to initial nurse visit had the
      longest LOS, with Friday operations being most delayed. A contributing factor may
      be absence of ostomy teaching over the weekend.

PMID- 27046796
TI  - The role of axillofemoral bypass in current vascular surgery practice.
AB  - BACKGROUND: In the era of increasing endovascular approaches for aortoiliac
      disease, we sought to determine the role of axillofemoral bypass in contemporary
      practice. METHODS: All axillofemoral bypasses performed at our institution from
      2006 to 2013 were reviewed for indication, patency, and survival and compared
      with our prior published series before the widespread use of endovascular
      techniques (1996 to 2001). RESULTS: During the study period, 90 bypasses (29
      axillofemoral and 61 axillobifemoral) bypasses were performed. The number of
      procedures performed decreased from an average of 24 to 12 procedures per year in
      historical and contemporary groups, respectively. Indications have changed
      significantly with more urgent or emergent procedures. Overall patency at 1 and 2
      years was 74.6% and 67.8%, respectively. Median survival was 40.3 months, with
      overall survival 67.0% and 54.2% at 1 and 2 years, respectively. CONCLUSIONS:
      Axillofemoral bypass is an increasingly uncommon procedure and more likely
      performed for limb salvage in urgent or emergent settings.

PMID- 27046797
TI  - Emergent reversal of vitamin K antagonists: addressing all the factors.
AB  - BACKGROUND: Reversal of warfarin-induced coagulopathy after traumatic injury may
      be done exclusively with prothrombin complex concentrates (PCCs). No direct
      comparisons between different PCC regimens exist to guide clinical decision
      making. Our institution has used 2 distinct PCC strategies for warfarin reversal;
      a 3-Factor PCC (Profilnine) combined with activated Factor VII (3F-PCC+rVIIa),
      and a 4-Factor PCC (Kcentra) given without additional factor supplementation.
      METHODS: Retrospective review of all PCC administrations to trauma patients with
      acute bleeding who were taking warfarin before injury. Primary endpoints were
      international normalized ratio (INR) reduction, in-hospital mortality, and
      diagnosis of deep venous thrombosis (DVT). RESULTS: Eighty-seven patients were
      identified from 2011 to 2015. Fifty-three were treated with 3F-PCC+rVIIa and 34
      with 4F-PCC. Patient demographics, injury severity, and presenting laboratory
      data were similar. The 3F-PCC+rVIIa produced a lower median (IQR) INR
      postreversal compared with 4F-PCC (.75 (.69, 1.00) vs 1.28 (1.13, 1.36), P<.001).
      Both regimens were able to obtain an INR lower than 1.5 immediately after
      administration (3F+rVIIA 93.9% vs 4F 97.1%, P =.51). In the 4F-PCC group, there
      was a significant decrease in the incidence of DVT (2.9% vs 22.6%), P < .01), and
      a nonsignificant reduction in mortality (2.9% vs 17.0%, P = .08). CONCLUSIONS:
      Use of 4F-PCC for warfarin reversal after traumatic hemorrhage is associated with
      a less severe decrease in INR, a significant reduction in DVT rates and a trend
      toward reduced mortality when compared with similar patients treated with 3F
      PCC+rVIIa.

PMID- 27046798
TI  - High dose antithrombin supplementation in early preeclampsia: A randomized,
      double blind, placebo-controlled study.
AB  - INTRODUCTION: Antithrombin levels are often reduced in preeclampsia and infusion
      of antithrombin concentrates has been reported to prolong gestation in severe
      preeclampsia. We aimed to evaluate efficacy and safety of high-dose antithrombin
      (ATIII) supplementation in patients with single pregnancies and preeclampsia
      occurring before 30 weeks of gestation. MATERIALS AND METHODS: In November 2004 a
      double-blind, placebo-controlled trial (code KB033) was started in 13 Italian
      centers. The planned sample size was of 240 patients (intention-to-treat, ITT
      population) to detect a 30% relative risk reduction of the primary endpoint,
      composite perinatal morbidity. Eligible patients were randomized to high dose AT
      (3000 IU/daily, ATIII Kedrion S.p.A., Italy), or placebo (1% glycine) for 7 days
      or less until delivery, whichever came first. The per-protocol (PP) population
      was restricted to patients receiving at least two days of treatment. RESULTS: The
      study was terminated by the sponsor in October 2007 after the enrolment of 38
      evaluable patients - 20 randomized to high dose AT and 18 to placebo, 27 treated
      for 2 days or more - out of 164 screened patients. Enrolment failures were mainly
      represented by requirement for immediate delivery and consent refusal (91
      patients). The primary endpoint occurred in 15 of 38 patients (39.5%), with a
      relative risk in the AT arm of 0.85 (95% CI 0.42-1.75) and 0.79 (95% CI 0.30
      2.11) in the ITT and PP populations, respectively. Living neonates in the two
      arms had similar weight at birth, Apgar scores, and duration of hospitalization
      in neonatal ICU. In mothers, AT supplementation was associated with reduced blood
      loss at delivery and with surrogate laboratory markers (LDH, d-dimer).
      CONCLUSIONS: The results of this markedly underpowered trial, albeit suggestive
      of a potential maternal benefit, cannot support high-dose AT supplementation to
      improve fetal/neonatal outcomes in early preeclampsia.

PMID- 27046799
TI  - Understanding cardiovascular risk in hemophilia: A step towards prevention and
      management.
AB  - Advances in hemophilia care have led to increased life expectancy and new
      challenges in the management of the aging hemophilia population, including
      cardiovascular risk. Despite the deep knowledge into cardiovascular disease in
      terms of pathophysiology, risk prediction, prevention, early detection and
      management gained over the last decades, studies in hemophiliacs are scarce and
      mainly descriptive. As a growing amount of evidence points towards a similar or
      increased prevalence of traditional cardiovascular risk factors in hemophilia
      compared to the general population, the role of non-traditional, disease-related
      and treatment-related cardiovascular risk factors remains under investigation.
      Better understanding of cardiovascular risk in hemophilia is mandatory for proper
      cardiovascular risk prevention and management. Therefore, this review aims to
      summarize current knowledge on cardiovascular risk in hemophilia patients
      focusing on a) cardiovascular risk factors (traditional, non-traditional, disease
      related and treatment-related), b) cardiovascular morbidity and mortality and c)
      cardiovascular prevention and management. 

PMID- 27046800
TI  - Paradoxical Hemodynamic Instability After Pericardial Window.
AB  - Paradoxical hemodynamic instability (PHI), also called postoperative low cardiac
      output syndrome (LCOS), is a rare but fatal complication after drainage of a
      pericardial effusion (PEf). This condition usually develops within hours
      postprocedure and appears unrelated to the method of drainage. The exact
      mechanism of this condition is not well understood. We present a case of an 84
      year-old patient with no previous cardiac or cancer history who presented with
      acute shortness of breath (SOB). Computed tomography (CT) ruled out pulmonary
      embolism and echocardiography confirmed early tamponade. Following emergent
      subxiphoid pericardiectomy, the patient developed hemodynamic instability and
      shock and subsequent multiorgan failure. Repeat echocardiography revealed left
      ventricular (LV) hypercontractility and new right ventricular (RV) dilatation
      with akinesis. The patient's condition continued to deteriorate in spite of
      maximal doses of pressors. The patient died after the family's request to
      discontinue further extraordinary measures. 

PMID- 27046801
TI  - Towards person-centredness in aged care - exploring the impact of leadership.
AB  - AIM: To explore the association between leadership behaviours among managers in
      aged care, and person-centredness of care and the psychosocial climate.
      BACKGROUND: Theory suggests that leadership is important for improving person
      centredness in aged care, however, empirical evidence is lacking. METHODS: A
      cross-sectional design was used to collect data from Swedish aged care staff (n =
      3661). Valid and reliable questionnaires assessing leadership behaviours, person
      centeredness of care and the psychosocial climate were used. Data were analysed
      using multiple linear regression including interaction terms. RESULTS: Leadership
      behaviours were significantly related to the person-centredness of care and the
      psychosocial climate. The level of person-centredness of care moderated the
      impact of leadership on the psychosocial climate. CONCLUSIONS AND IMPLICATIONS
      FOR NURSING MANAGEMENT: The leadership behaviour of managers significantly
      impacts person-centred care practice and contributes to the psychosocial climate
      for both staff and residents in aged care. This study is the first empirically to
      confirm that middle managers have a central leadership role in developing and
      supporting person-centred care practice, thereby creating a positive psychosocial
      climate and high quality care.

PMID- 27046802
TI  - Qigong or Yoga Versus No Intervention in Older Adults With Chronic Low Back Pain
      A Randomized Controlled Trial.
AB  - The aim of this study was to assess the effectiveness of the reduction of chronic
      lower back pain in older adults using either yoga classes or qigong classes
      compared with no intervention. Older adults (65 years of age and older) with
      chronic low back pain were enrolled in and randomly allocated to: 1) yoga (24
      classes, 45 minutes each, during 3 months), 2) qigong (12 classes, 90 minutes
      each, during 3 months), or 3) a control group who received no additional
      intervention. The pain intensity item of the Functional Rating Index after 3
      months was used as primary outcome parameter. A total of 176 patients were
      randomized (n = 61 yoga, n = 58 qigong, n = 57 control; mean age 73 +/- 5.6
      years, 89% female). The mean adjusted pain intensity after 3 months was 1.71 for
      the yoga group (95% confidence interval [CI], 1.54-1.89), 1.67 for the qigong
      group (95% CI, 1.45-1.89), and 1.89 for no intervention (95% CI, 1.67-2.11). No
      statistically significant group differences were observed. Possible explanations
      for this lack of pain relief might include the ineffectiveness of interventions,
      inappropriate outcomes, or differences in pain perception and processing in older
      adults. PERSPECTIVE: The aim of this study was to assess the effectiveness of the
      reduction of chronic lower back pain in older adults using either yoga classes or
      qigong classes compared with no intervention. This 3-armed randomized trial with
      176 older adults showed that yoga and qigong were not superior to no treatment in
      reducing pain and increasing quality of life.

PMID- 27046803
TI  - Inter-rater reliability study of the PeritronTM perineometer in pregnant women.
AB  - OBJECTIVE: To assess the inter-rater reliability of two raters for the mean and
      single maximal value of three vaginal maximum voluntary contractions (MVCs) using
      the PeritronTM perineometer for study participants in the first and second
      trimesters of pregnancy. PARTICIPANTS: Thirty-six low-risk pregnant women.
      METHODS: The assessments were done by two different examiners with an interval of
      2 to 7 days. For statistical analysis, the concordance correlation coefficient
      (CCC) and Bland-Altman limits of agreement were used. RESULTS: For the overall
      sample, good reliability of 0.80 was found analyzing the mean of three MVCs and
      for the single maximal value (CCC = 0.79). Good reliability was found for the
      mean of three MVCs (0.81 and 0.78) for the first and second trimesters,
      respectively. Good reliability of 0.89 was found in the first trimester and a
      moderate reliability of 0.70 for the second trimester when analyzing the single
      maximal value of three MVCs. CONCLUSION: Good inter-rater reliability was found
      for the overall sample and first trimester of pregnancy for both mean values and
      single maximal values of the three MVCs. A good and moderate reliability was
      respectively found in the second trimester in analyzing the mean and single
      maximum values of three MVCs.

PMID- 27046804
TI  - Risk factors for periventricular echodensities and outcomes in preterm infants.
AB  - OBJECTIVES: To determine the incidence, risk factors and outcomes associated with
      transient and/or persistent periventricular echodensities (PVED) among preterm
      infants. METHODS: Medical records of preterm infants born at <= 32 weeks
      gestational age (GA) with PVED and no other brain pathology were reviewed and
      compared to matched control infants in a case-controlled retrospective study.
      Neurodevelopmental outcomes at 8-24 months corrected age were documented.
      RESULTS: A 17.8% incidence of PVED was recorded, with the highest incidence of 30
      40% recorded at 29-31 weeks GA. Study and control groups were similar for all
      maternal parameters and neonatal morbidities, except for a higher incidence of
      respiratory distress syndrome among the study group. PVED at one month of age was
      predicted by 5 min Apgar score < 7 [OR = 33.78 (CI 2.94-388.06, p = 0.005)]. PVED
      was not associated with long-term neurodevelopmental disability. CONCLUSIONS: No
      risk factors or specific associated morbidities were identified among preterm
      infants with transient PVED. PVED at one month of age was predicted by low 5 min
      Apgar scores, possibly suggesting different pathogenesis or timing between the
      groups. Long-term outcome studies are needed to determine PVED impact.

PMID- 27046805
TI  - Bogong moths.
AB  - A quick guide to the Australian Bogong moth, the nocturnal counterpart of the
      migratory Monarch butterfly. 

PMID- 27046806
TI  - Flying starlings, PET and the evolution of volant dinosaurs.
AB  - Birds have evolved behavioral and morphological adaptations for powered flight.
      Many aspects of this transition are unknown, including the neuroanatomical
      changes that made flight possible [1]. To understand how the avian brain drives
      this complex behavior, we utilized positron emission tomography (PET) scanning
      and the tracer (18)F-fluorodeoxyglucose (FDG) to document regional metabolic
      activity in the brain associated with a variety of locomotor behaviors. FDG
      studies are typically employed in rats [2] though the technology has been applied
      to birds [3]. We examined whole-brain function in European Starlings (Sturnus
      vulgaris), trained to fly in a wind tunnel while metabolizing the tracer. Drawing
      on predictions from early anatomical studies [4], we hypothesized increased
      metabolic activity in the Wulst and functionally related visual brain regions
      during flight. We found that flight behaviors correlated positively with
      entopallia and Wulst activity, but negatively with thalamic activity.

PMID- 27046807
TI  - Direct and indirect dorsolateral striatum pathways reinforce different action
      strategies.
AB  - The basal ganglia, and the striatum in particular, are critical for action
      reinforcement [1,2]. The dorsal striatum, which can be further subdivided into
      dorsomedial (DMS) and dorsolateral (DLS) striatum, is mainly composed of two
      subpopulations of striatal medium spiny projection neurons (MSNs): dopamine D1
      receptor-expressing MSNs that constitute the striatonigral or direct pathway
      (dMSNs); and dopamine D2 receptor-expressing MSNs that constitute the
      striatopallidal or indirect pathway (iMSNs) [3]. It has been suggested that each
      pathway has opposing roles in reinforcement, with dMSNs being important to learn
      positive reinforcement and iMSNs to learn to avoid undesired actions (Go/No-Go)
      [1]. Furthermore, optogenetic self-stimulation of dMSNs in DMS leads to
      reinforcement of actions, while self-stimulation of iMSNs leads to avoidance of
      actions [2]. However, in DLS, which has been implicated in the consolidation of
      well-trained actions and habits in mice [4,5], both pathways are active during
      lever-pressing for reward [6]. Furthermore, extensive skill training leads to
      long-lasting potentiation of glutamatergic inputs into both dMSNs and iMSNs [4].
      We report here that, in DLS, both dMSNs and iMSNs are involved in positive
      reinforcement, but support different action strategies.

PMID- 27046808
TI  - Encoding four gene expression programs in the activation dynamics of a single
      transcription factor.
AB  - Cellular signaling response pathways often exhibit a bow-tie topology [1,2]:
      multiple upstream stress signals converge on a single shared transcription
      factor, which is thought to induce different downstream gene expression programs
      (Figure 1A). However, if several different signals activate the same
      transcription factor, can each signal then induce a specific gene expression
      response? A growing body of literature supports a temporal coding theory where
      information about environmental signals can be encoded, at least partially, in
      the temporal dynamics of the shared transcription factor [1,2]. For example, in
      the case of the budding yeast transcription factor Msn2, different stresses
      induce distinct Msn2 activation dynamics: Msn2 shows pulsatile nuclear activation
      with dose-dependent frequency under glucose limitation, but sustained nuclear
      activation with dose-dependent amplitude under oxidative stress [3]. These
      dynamic patterns can then lead to differential gene expression responses [3-5],
      but it is not known how much specificity can be obtained. Thus, a major question
      of this temporal coding theory is how many gene response programs or cellular
      functions can be robustly encoded by dynamic control of a single transcription
      factor. Here we provide the first direct evidence that, simply by regulating the
      activation dynamics of a single transcription factor, it is possible to
      preferentially induce four distinct gene expression programs.

PMID- 27046809
TI  - Ancestral sleep.
AB  - While we do not yet understand all the functions of sleep, its critical role for
      normal physiology and behaviour is evident. Its amount and temporal pattern
      depend on species and condition. Humans sleep about a third of the day with the
      longest, consolidated episode during the night. The change in lifestyle from
      hunter-gatherers via agricultural communities to densely populated industrialized
      centres has certainly affected sleep, and a major concern in the medical
      community is the impact of insufficient sleep on health [1,2]. One of the causal
      mechanisms leading to insufficient sleep is altered exposure to the natural light
      dark cycle. This includes the wide availability of electric light, attenuated
      exposure to daylight within buildings, and evening use of light-emitting devices,
      all of which decrease the strength of natural light-dark signals that entrain
      circadian systems [3]. 

PMID- 27046810
TI  - Response to de la Iglesia et al.
AB  - We wish to respond to the commentary of de la Iglesia et al. [1]. Studies
      comparing sleep in different communities have different goals. One frequent goal
      has been to determine how sleep is affected by manipulating specific 'modern'
      conditions. Many studies have investigated the effect of artificial light and
      electronic entertainment. Such studies have clearly shown that light,
      particularly blue light, delays sleep onset [2]. Studying the effect of
      artificial light on sleep was not a goal of our study. 

PMID- 27046811
TI  - Microbiology: Mixing Wine, Chocolate, and Coffee.
AB  - Yeasts associated with cocoa and coffee beans are genetically distinct. These
      populations have been created through the migration and mixing of populations
      associated with vineyards, trees in America, and the ancestral seat of this
      species in Far East Asia. 

PMID- 27046812
TI  - Spatial Cognition: Grid Cells Support Imagined Navigation.
AB  - Grid cells in the entorhinal cortex represent an animal's current location during
      navigation. A new study indicates that grid cells in humans also represent
      information about imagined movement and spatial orienting, suggesting that the
      entorhinal network has a flexible role in spatial representation.

PMID- 27046813
TI  - Anthropology: The Long Lives of Fairy Tales.
AB  - Anthropologists, borrowing techniques from evolutionary biology, have
      demonstrated that some common fairy tales can be traced back 5,000 years, or
      more, long before the development of written traditions.

PMID- 27046814
TI  - Neuroscience: Suppressing One Drive for a Chance to Satisfy Another.
AB  - Food deprivation suppresses sleep, presumably to increase time available for
      foraging. A new study identifies a conserved gene, Translin, as a modulator of
      sleep in response to metabolic changes. 

PMID- 27046815
TI  - Evolution: Five Heads Are Better Than One.
AB  - Three newly discovered species of fig-living nematodes display remarkable
      diversity in head morphology depending on their local environment. This shows
      that a great deal of ecological diversity can be maintained in the absence of
      substantial genetic variation. 

PMID- 27046816
TI  - GPCR Signaling: beta-arrestins Kiss and Remember.
AB  - beta-arrestin-dependent activation of the ERK MAP kinase downstream of GPCRs
      typically originates from internalized receptor-beta-arrestin-ERK complexes. A
      new study now reports that beta-arrestin 2 is sufficiently 'primed' after
      'kissing' the beta1-adrenergic receptor to initiate ERK activation even in the
      absence of formation of the receptor-beta-arrestin-ERK complex and receptor
      internalization.

PMID- 27046817
TI  - Cognitive Neuroscience: The Neural Basis of Motor Learning by Observing.
AB  - Somatosensory feedback from the limbs plays an essential role when we learn to
      make new movements. A recent study shows that motor learning can be accomplished
      purely through observation, and motor learning by observing also critically
      depends on the brain's somatosensory system. 

PMID- 27046818
TI  - Motor Control: Illuminating an Enigmatic Midbrain Locomotor Center.
AB  - A recent study has functionally disentangled the hitherto enigmatic mesencephalic
      locomotor region of the brain on the basis of cell type diversity and identified
      differential upstream regulatory pathways. 

PMID- 27046819
TI  - Mate Choice: Charting Desire's Tangled Bank.
AB  - Choosing a mate requires a way to turn sexual arousal into sexual action. A
      recent paper identifies a hormone receptor that acts as a molecular gatekeeper in
      reproductive decisions. Focusing on mate-choice mechanisms may clarify
      longstanding evolutionary puzzles in sexual selection and speciation. 

PMID- 27046820
TI  - Evolutionary and Environmental Forces Sculpting Leaf Development.
AB  - Leaf shape is spectacularly diverse. As a major component of plant architecture
      and an interface for light capture, gas exchange, and thermoregulation, the
      potential contributions of leaves to plant fitness are innumerable. Particularly
      because of their intimate association and interaction with the surrounding
      environment, both the plasticity of leaf shape during the lifetime of a plant and
      the evolution of leaf shape over geologic time are revealing with respect to leaf
      function. Leaf shapes arise within a developmental context that constrains both
      their evolution and environmental plasticity. Quantitative models capturing
      genetic diversity, developmental context, and environmental plasticity will be
      required to fully understand the evolution and development of leaf shape and its
      response to environmental pressures. In this review, we discuss recent literature
      demonstrating that distinct molecular pathways are modulated by specific
      environmental inputs, the output of which regulates leaf dissection. We propose a
      synthesis explaining both historical patterns in the paleorecord and conserved
      plastic responses in extant plants. Understanding the potential adaptive value of
      leaf shape, and how to molecularly manipulate it, will prove to be invaluable in
      designing crops optimized for future climates.

PMID- 27046821
TI  - Introduction of a National Minimum Wage Reduced Depressive Symptoms in Low-Wage
      Workers: A Quasi-Natural Experiment in the UK.
AB  - Does increasing incomes improve health? In 1999, the UK government implemented
      minimum wage legislation, increasing hourly wages to at least L3.60. This policy
      experiment created intervention and control groups that can be used to assess the
      effects of increasing wages on health. Longitudinal data were taken from the
      British Household Panel Survey. We compared the health effects of higher wages on
      recipients of the minimum wage with otherwise similar persons who were likely
      unaffected because (1) their wages were between 100 and 110% of the eligibility
      threshold or (2) their firms did not increase wages to meet the threshold. We
      assessed the probability of mental ill health using the 12-item General Health
      Questionnaire. We also assessed changes in smoking, blood pressure, as well as
      hearing ability (control condition). The intervention group, whose wages rose
      above the minimum wage, experienced lower probability of mental ill health
      compared with both control group 1 and control group 2. This improvement
      represents 0.37 of a standard deviation, comparable with the effect of
      antidepressants (0.39 of a standard deviation) on depressive symptoms. The
      intervention group experienced no change in blood pressure, hearing ability, or
      smoking. Increasing wages significantly improves mental health by reducing
      financial strain in low-wage workers. (c) 2016 The Authors. Health Economics
      published by John Wiley & Sons Ltd.

PMID- 27046822
TI  - A new antibacterial lupane ester from the seeds of Acokanthera oppositifolia Lam.
AB  - As a part of ongoing investigation of Acokanthera oppositifolia (Lam.) Codd.,
      four compounds were isolated from its seeds, a new compound; lup-20(29)-en-3beta
      O-(3'-beta-hydroxy) palmitate (1), three known compounds; a triterpene; lupeol
      (2), a cardiac glycoside; acovenoside A (3) and a sterol; beta-sitosterol (4).
      Their structures were investigated using 1D & 2D- 1H and 13CNMR spectroscopy.
      Antimicrobial potential of the compounds was evaluated against 10 microorganisms
      responsible for endocarditis. The minimum inhibitory concentration (MIC) of the
      compounds was determined using broth microdilution method. The new compound (1)
      evidenced significant antibacterial activity especially aganist Pseudomonas
      aeruginosa with (MIC 7.81 MUg/ml). Lupeol (2) exhibited remarkable antimicrobial
      activity against Methicillin-resistant Staphylococcus aureus, Aspergillus
      fumigates and Candida albicans (MIC 3.9, 0.24 and 3.9 MUg/ml, respectively). On
      the other hand, acovenoside A (3) inhibited the growth of Escherichia coli (MIC
      0.98 MUg/ml). We herein present the potential of A. oppositifolia as a
      cardioprotective agent against the microorganisms responsible for endocarditis.

PMID- 27046823
TI  - Krebs Cycle Moonlights in Caspase Regulation.
AB  - In this issue of Developmental Cell, Aram et al. (2016) identify a mechanism that
      uses a Krebs cycle protein to control local activation of a ubiquitin ligase
      complex at the mitochondrial outer membrane for temporally and spatially
      restricted caspase activation during Drosophila sperm differentiation.

PMID- 27046824
TI  - Epithelial Contractility: A Crowning Achievement.
AB  - Epithelial cells transmit contractile force with adherens junctions to mediate
      morphological changes like the extrusion of apoptotic cells. In this issue of
      Developmental Cell, Michael and colleagues (2016) show that the actin binding
      protein Coronin plays a critical role in actin cytoskeleton reorganization and
      association with junctions to promote contractility.

PMID- 27046825
TI  - A Female Identity Switch Helps Keep Only One Egg in the Basket.
AB  - The flowering plant female gametophyte carries two gametes, an egg cell and a
      central cell, whose double fertilization gives rise to embryo and endosperm,
      respectively. In this issue of Developmental Cell, Yuan et al. (2016) identify
      the protein CKI1 as a key switch that controls the differential female gamete
      identities.

PMID- 27046826
TI  - Nursing the Follicles.
AB  - In a recent issue of Science, Lei and Spradling (2016) uncover how germ cells
      differentiate into oocytes in mouse embryos. Mouse germ cells form cysts, in
      which sister cells nurse the developing oocyte by donating their organelles and
      cytoplasmic materials.

PMID- 27046827
TI  - mRNAs Hit a Sticky Wicket.
AB  - Drosophila germ cell specification depends on localization of mRNAs required for
      patterning to the posterior of the oocyte during oogenesis. In a recent issue of
      Nature, Vourekas et al. (2016) suggest that Aubergine in complex with piRNAs may
      provide a low-specificity anchoring mechanism for posterior mRNAs.

PMID- 27046828
TI  - Actin'g against the Ball and Chain.
AB  - Spinocerebellar ataxia type 13 is a rare autosomal-dominant neurodegenerative
      disease induced by mutations in the voltage-dependent Kv3.3 potassium channel.
      Recently in Cell, Zhang et al. (2016) provide new insights into how Arp2/3
      dependent actin polymerization modulates both Kv3.3 activity and its ability to
      stimulate actin polymerization via Hax-1.

PMID- 27046829
TI  - The Rationale of the Inevitable, or Why Is the Consideration of Repetitive DNA
      Elements Indispensable in Studies of Sperm Nucleosomes.

PMID- 27046830
TI  - The CKI1 Histidine Kinase Specifies the Female Gametic Precursor of the
      Endosperm.
AB  - Since the discovery of double fertilization, it has been recognized that
      flowering plants produce two highly dimorphic female gametes, the egg cell and
      central cell. These give rise, respectively, to the embryo and the endosperm, a
      nourishing tissue unique to flowering plants. Here we show that in Arabidopsis,
      endosperm formation requires the CYTOKININ INDEPENDENT 1 (CKI1) histidine kinase,
      an activator of the cytokinin signaling pathway, which specifies central cells
      and restricts egg cell fate. Dimorphism of the two adjacent gametes is
      mechanistically established in the syncytial embryo sac by spatially restricted
      CKI1 expression, followed by translocation of ER-localized CKI1 protein via
      nuclear migration. Cell specification by CKI1 likely involves activation of the
      cytokinin signaling pathway mediated by histidine phosphotransferases. Ectopic
      CKI1 expression generates non-propagating seeds with dual fertilized endosperms
      and no embryos. We conclude that CKI1-directed specification of the endosperm
      precursor central cell results in seeds containing an embryo and an endosperm. 

PMID- 27046831
TI  - SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/beta
      Catenin and Hippo/YAP Signaling.
AB  - Intestinal tumorigenesis is a result of mutations in signaling pathways that
      control cellular proliferation, differentiation, and survival. Mutations in the
      Wnt/beta-catenin pathway are associated with the majority of intestinal cancers,
      while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an
      emerging regulator of intestinal tumorigenesis. In addition, these closely
      related pathways play a central role during intestinal regeneration. We have
      previously shown that methylation of the Hippo transducer YAP by the lysine
      methyltransferase SETD7 controls its subcellular localization and function. We
      now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and
      regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1,
      and beta-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced
      nuclear accumulation of beta-catenin. Collectively, these results define a
      methyltransferase-dependent regulatory mechanism that links the Wnt/beta-catenin
      and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.

PMID- 27046832
TI  - Coronin 1B Reorganizes the Architecture of F-Actin Networks for Contractility at
      Steady-State and Apoptotic Adherens Junctions.
AB  - In this study we sought to identify how contractility at adherens junctions
      influences apoptotic cell extrusion. We first found that the generation of
      effective contractility at steady-state junctions entails a process of
      architectural reorganization whereby filaments that are initially generated as
      poorly organized networks of short bundles are then converted into co-aligned
      perijunctional bundles. Reorganization requires coronin 1B, which is recruited to
      junctions by E-cadherin adhesion and is necessary to establish contractile
      tension at the zonula adherens. When cells undergo apoptosis within an epithelial
      monolayer, coronin 1B is also recruited to the junctional cortex at the
      apoptotic/neighbor cell interface in an E-cadherin-dependent fashion to support
      actin architectural reorganization, contractility, and extrusion. We propose that
      contractile stress transmitted from the apoptotic cell through E-cadherin
      adhesions elicits a mechanosensitive response in neighbor cells that is necessary
      for the morphogenetic event of apoptotic extrusion to occur.

PMID- 27046833
TI  - Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic
      Instability at Microtubule Plus- and Minus-Ends.
AB  - The assembly of microtubule-based cellular structures depends on regulated
      tubulin polymerization and directional transport. Here, we purify and
      characterize tubulin heterodimers that have human beta-tubulin isotype III
      (TUBB3), as well as heterodimers with one of two beta-tubulin mutations (D417H or
      R262H). Both point mutations are proximal to the kinesin-binding site and have
      been linked to an ocular motility disorder in humans. Compared to wild-type,
      microtubules with these mutations have decreased catastrophe frequencies and
      increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly,
      the D417H mutation does not alter microtubule lattice structure or Mal3 binding
      to growing filaments. Instead, this mutation reduces the affinity of tubulin for
      TOG domains and colchicine, suggesting that the distribution of tubulin
      heterodimer conformations is changed. Together, our findings reveal how residues
      on the surface of microtubules, distal from the GTP-hydrolysis site and inter
      subunit contacts, can alter polymerization dynamics at the plus- and minus-ends
      of microtubules. 

PMID- 27046834
TI  - An FGFR1-SPRY2 Signaling Axis Limits Basal Cell Proliferation in the Steady-State
      Airway Epithelium.
AB  - The steady-state airway epithelium has a low rate of stem cell turnover but can
      nevertheless mount a rapid proliferative response following injury. This suggests
      a mechanism to restrain proliferation at steady state. One such mechanism has
      been identified in skeletal muscle in which pro-proliferative FGFR1 signaling is
      antagonized by SPRY1 to maintain satellite cell quiescence. Surprisingly, we
      found that deletion of Fgfr1 or Spry2 in basal cells of the adult mouse trachea
      caused an increase in steady-state proliferation. We show that in airway basal
      cells, SPRY2 is post-translationally modified in response to FGFR1 signaling.
      This allows SPRY2 to inhibit intracellular signaling downstream of other receptor
      tyrosine kinases and restrain basal cell proliferation. An FGFR1-SPRY2 signaling
      axis has previously been characterized in cell lines in vitro. We now demonstrate
      an in vivo biological function of this interaction and thus identify an active
      signaling mechanism that maintains quiescence in the airway epithelium.

PMID- 27046835
TI  - Alternative Computational Analysis Shows No Evidence for Nucleosome Enrichment at
      Repetitive Sequences in Mammalian Spermatozoa.
AB  - Samans et al. (2014) reported the enrichment of nucleosomes in human and bovine
      spermatozoa at centromere repeats and retrotransposon sequences such as LINE-1
      and SINE. We demonstrate here that nucleosomal enrichments at repetitive
      sequences as reported result from bioinformatic analyses that make redundant use
      of sequencing reads that map to multiple locations in the genome. To illustrate
      that this computational approach is flawed, we observed comparable artificial
      enrichments at repetitive sequences when aligning control genomic DNA or
      simulated reads of uniform genome coverage. These results imply that the main
      conclusions of the article by Samans et al. (2014) are confounded by an
      inappropriate computational methodology used to analyze the primary data.

PMID- 27046836
TI  - Productivity Growth in the English National Health Service from 1998/1999 to
      2013/2014.
AB  - Productivity growth is a key measure against which National Health Service (NHS)
      achievements are judged. We measure NHS productivity growth as a set of paired
      year-on-year comparisons from 1998/1999-1999/2000 through 2012/2013-2013/2014,
      which are converted into a chained index that summarises productivity growth over
      the entire period. Our measure is as comprehensive as data permit and accounts
      for the multitude of diverse outputs and inputs involved in the production
      process and for regular revisions to the data used to quantify outputs and
      inputs. Over the full-time period, NHS output increased by 88.96% and inputs by
      81.58%, delivering overall total factor productivity growth of 4.07%.
      Productivity growth was negative during the first two terms of Blair's
      government, with average yearly growth rate of -1.01% per annum (pa) during the
      first term (to 2000/2001) and -1.49% pa during the second term (2000/2001
      2004/2005). Productivity growth was positive under Blair's third term (2004/2005
      2007/2008) at 1.41% pa and under the Brown government (2007/2008-2010/2011),
      averaging 1.13% pa. Productivity growth remained positive under the Coalition
      (2010/2011-2013/2014), averaging 1.56% pa. (c) 2016 The Authors Health Economics
      Published by John Wiley & Sons Ltd.

PMID- 27046837
TI  - Archetypal Analysis for Nominal Observations.
AB  - Archetypal analysis is a popular exploratory tool that explains a set of
      observations as compositions of few 'pure' patterns. The standard formulation of
      archetypal analysis addresses this problem for real valued observations by
      finding the approximate convex hull. Recently, a probabilistic formulation has
      been suggested which extends this framework to other observation types such as
      binary and count. In this article we further extend this framework to address the
      general case of nominal observations which includes, for example, multiple-option
      questionnaires. We view archetypal analysis in a generative framework: this
      allows explicit control over choosing a suitable number of archetypes by
      assigning appropriate prior information, and finding efficient update rules using
      variational Bayes'. We demonstrate the efficacy of this approach extensively on
      simulated data, and three real world examples: Austrian guest survey dataset,
      German credit dataset, and SUN attribute image dataset. 

PMID- 27046838
TI  - Bayesian Nonparametric Clustering for Positive Definite Matrices.
AB  - Symmetric Positive Definite (SPD) matrices emerge as data descriptors in several
      applications of computer vision such as object tracking, texture recognition, and
      diffusion tensor imaging. Clustering these data matrices forms an integral part
      of these applications, for which soft-clustering algorithms (K-Means, expectation
      maximization, etc.) are generally used. As is well-known, these algorithms need
      the number of clusters to be specified, which is difficult when the dataset
      scales. To address this issue, we resort to the classical nonparametric Bayesian
      framework by modeling the data as a mixture model using the Dirichlet process
      (DP) prior. Since these matrices do not conform to the Euclidean geometry, rather
      belongs to a curved Riemannian manifold,existing DP models cannot be directly
      applied. Thus, in this paper, we propose a novel DP mixture model framework for
      SPD matrices. Using the log-determinant divergence as the underlying
      dissimilarity measure to compare these matrices, and further using the connection
      between this measure and the Wishart distribution, we derive a novel DPM model
      based on the Wishart-Inverse-Wishart conjugate pair. We apply this model to
      several applications in computer vision. Our experiments demonstrate that our
      model is scalable to the dataset size and at the same time achieves superior
      accuracy compared to several state-of-the-art parametric and nonparametric
      clustering algorithms. 

PMID- 27046839
TI  - Learning Deep Representation for Face Alignment with Auxiliary Attributes.
AB  - In this study, we show that landmark detection or face alignment task is not a
      single and independent problem. Instead, its robustness can be greatly improved
      with auxiliary information. Specifically, we jointly optimize landmark detection
      together with the recognition of heterogeneous but subtly correlated facial
      attributes, such as gender, expression, and appearance attributes. This is non
      trivial since different attribute inference tasks have different learning
      difficulties and convergence rates. To address this problem, we formulate a novel
      tasks-constrained deep model, which not only learns the inter-task correlation
      but also employs dynamic task coefficients to facilitate the optimization
      convergence when learning multiple complex tasks. Extensive evaluations show that
      the proposed task-constrained learning (i) outperforms existing face alignment
      methods, especially in dealing with faces with severe occlusion and pose
      variation, and (ii) reduces model complexity drastically compared to the state-of
      the-art methods based on cascaded deep model. 

PMID- 27046840
TI  - Sequential Non-Rigid Structure from Motion Using Physical Priors.
AB  - We propose a new approach to simultaneously recover camera pose and 3D shape of
      non-rigid and potentially extensible surfaces from a monocular image sequence.
      For this purpose, we make use of the Extended Kalman Filter based Simultaneous
      Localization And Mapping (EKF-SLAM) formulation, a Bayesian optimization
      framework traditionally used in mobile robotics for estimating camera pose and
      reconstructing rigid scenarios. In order to extend the problem to a deformable
      domain we represent the object's surface mechanics by means of Navier's
      equations, which are solved using a Finite Element Method (FEM). With these main
      ingredients, we can further model the material's stretching, allowing us to go a
      step further than most of current techniques, typically constrained to surfaces
      undergoing isometric deformations. We extensively validate our approach in both
      real and synthetic experiments, and demonstrate its advantages with respect to
      competing methods. More specifically, we show that besides simultaneously
      retrieving camera pose and non-rigid shape, our approach is adequate for both
      isometric and extensible surfaces, does not require neither batch processing all
      the frames nor tracking points over the whole sequence and runs at several frames
      per second. 

PMID- 27046841
TI  - Socially Constrained Structural Learning for Groups Detection in Crowd.
AB  - Modern crowd theories agree that collective behavior is the result of the
      underlying interactions among small groups of individuals. In this work, we
      propose a novel algorithm for detecting social groups in crowds by means of a
      Correlation Clustering procedure on people trajectories. The affinity between
      crowd members is learned through an online formulation of the Structural SVM
      framework and a set of specifically designed features characterizing both their
      physical and social identity, inspired by Proxemic theory, Granger causality, DTW
      and Heat-maps. To adhere to sociological observations, we introduce a loss
      function ( G -MITRE) able to deal with the complexity of evaluating group
      detection performances. We show our algorithm achieves state-of-the-art results
      when relying on both ground truth trajectories and tracklets previously extracted
      by available detector/tracker systems. 

PMID- 27046842
TI  - Fast Multidimensional Ellipsoid-Specific Fitting by Alternating Direction Method
      of Multipliers.
AB  - Many problems in computer vision can be formulated as multidimensional ellipsoid
      specific fitting, which is to minimize the residual error such that the
      underlying quadratic surface is a multidimensional ellipsoid. In this paper, we
      present a fast and robust algorithm for solving ellipsoid-specific fitting
      directly. Our method is based on the alternating direction method of multipliers,
      which does not introduce extra positive semi-definiteness constraints. The
      computation complexity is thus significantly lower than those of semi-definite
      programming (SDP) based methods. More specifically, to fit n data points into a p
      dimensional ellipsoid, our complexity is O(p(6) + np(4))+O(p(3)), where the
      former O results from preprocessing data once, while that of the state-of-the-art
      SDP method is O(p(6) + np(4) + n(3/2)p(2)) for each iteration. The storage
      complexity of our algorithm is about 1/2np(2), which is at most 1/4 of those of
      SDP methods. Extensive experiments testify to the great speed and accuracy
      advantages of our method over the state-of-the-art approaches. The implementation
      of our method is also much simpler than SDP based methods.

PMID- 27046843
TI  - Low Resolution Face Recognition Across Variations in Pose and Illumination.
AB  - We propose a completely automatic approach for recognizing low resolution face
      images captured in uncontrolled environment. The approach uses multidimensional
      scaling to learn a common transformation matrix for the entire face which
      simultaneously transforms the facial features of the low resolution and the high
      resolution training images such that the distance between them approximates the
      distance had both the images been captured under the same controlled imaging
      conditions. Stereo matching cost is used to obtain the similarity of two images
      in the transformed space. Though this gives very good recognition performance,
      the time taken for computing the stereo matching cost is significant. To overcome
      this limitation, we propose a reference-based approach in which each face image
      is represented by its stereo matching cost from a few reference images.
      Experimental evaluation on the real world challenging databases and comparison
      with the state-of-the-art super-resolution, classifier based and cross modal
      synthesis techniques show the effectiveness of the proposed algorithm. 

PMID- 27046844
TI  - High-Performance Personalized Heartbeat Classification Model for Long-Term ECG
      Signal.
AB  - Long-term electrocardiogram (ECG) has become one of the important diagnostic
      assist methods in clinical cardiovascular domain. Long-term ECG is primarily used
      for the detection of various cardiovascular diseases that are caused by various
      cardiac arrhythmia such as myocardial infarction, cardiomyopathy, and
      myocarditis. In the past few years, the development of an automatic heartbeat
      classification method has been a challenge. With the accumulation of medical
      data, personalized heartbeat classification of a patient has become possible. For
      the long-term data accumulation method, such as the holter, it is difficult to
      obtain the analysis results in a short time using the original method of serial
      design. The pressure to develop a personalized automatic classification model is
      high. To solve these challenges, this paper implemented a parallel general
      regression neural network (GRNN) to classify the heartbeat, and achieved a 95%
      accuracy according to the Association for the Advancement of Medical
      Instrumentation. We designed an online learning program to form a personalized
      classification model for patients. The achieved accuracy of the model is 88%
      compared to the specific ECG data of the patients. The efficiency of the parallel
      GRNN with GTX780Ti can improve by 450 times.

PMID- 27046846
TI  - Marginal Space Deep Learning: Efficient Architecture for Volumetric Image
      Parsing.
AB  - Robust and fast solutions for anatomical object detection and segmentation
      support the entire clinical workflow from diagnosis, patient stratification,
      therapy planning, intervention and follow-up. Current state-of-the-art techniques
      for parsing volumetric medical image data are typically based on machine learning
      methods that exploit large annotated image databases. Two main challenges need to
      be addressed, these are the efficiency in scanning high-dimensional parametric
      spaces and the need for representative image features which require significant
      efforts of manual engineering. We propose a pipeline for object detection and
      segmentation in the context of volumetric image parsing, solving a two-step
      learning problem: anatomical pose estimation and boundary delineation. For this
      task we introduce Marginal Space Deep Learning (MSDL), a novel framework
      exploiting both the strengths of efficient object parametrization in hierarchical
      marginal spaces and the automated feature design of Deep Learning (DL) network
      architectures. In the 3D context, the application of deep learning systems is
      limited by the very high complexity of the parametrization. More specifically 9
      parameters are necessary to describe a restricted affine transformation in 3D,
      resulting in a prohibitive amount of billions of scanning hypotheses. The
      mechanism of marginal space learning provides excellent run-time performance by
      learning classifiers in clustered, high-probability regions in spaces of
      gradually increasing dimensionality. To further increase computational efficiency
      and robustness, in our system we learn sparse adaptive data sampling patterns
      that automatically capture the structure of the input. Given the object
      localization, we propose a DL-based active shape model to estimate the non-rigid
      object boundary. Experimental results are presented on the aortic valve in
      ultrasound using an extensive dataset of 2891 volumes from 869 patients, showing
      significant improvements of up to 45.2% over the state-of-the-art. To our
      knowledge, this is the first successful demonstration of the DL potential to
      detection and segmentation in full 3D data with parametrized representations.

PMID- 27046845
TI  - Reproducibility in Computational Neuroscience Models and Simulations.
AB  - OBJECTIVE: Like all scientific research, computational neuroscience research must
      be reproducible. Big data science, including simulation research, cannot depend
      exclusively on journal articles as the method to provide the sharing and
      transparency required for reproducibility. METHODS: Ensuring model
      reproducibility requires the use of multiple standard software practices and
      tools, including version control, strong commenting and documentation, and code
      modularity. RESULTS: Building on these standard practices, model-sharing sites
      and tools have been developed that fit into several categories: 1) standardized
      neural simulators; 2) shared computational resources; 3) declarative model
      descriptors, ontologies, and standardized annotations; and 4) model-sharing
      repositories and sharing standards. CONCLUSION: A number of complementary
      innovations have been proposed to enhance sharing, transparency, and
      reproducibility. The individual user can be encouraged to make use of version
      control, commenting, documentation, and modularity in development of models. The
      community can help by requiring model sharing as a condition of publication and
      funding. SIGNIFICANCE: Model management will become increasingly important as
      multiscale models become larger, more detailed, and correspondingly more
      difficult to manage by any single investigator or single laboratory. Additional
      big data management complexity will come as the models become more useful in
      interpreting experiments, thus increasing the need to ensure clear alignment
      between modeling data, both parameters and results, and experiment.

PMID- 27046847
TI  - Abnormality Detection via Iterative Deformable Registration and Basis-Pursuit
      Decomposition.
AB  - We present a generic method for automatic detection of abnormal regions in
      medical images as deviations from a normative data base. The algorithm decomposes
      an image, or more broadly a function defined on the image grid, into the
      superposition of a normal part and a residual term. A statistical model is
      constructed with regional sparse learning to represent normative anatomical
      variations among a reference population (e.g., healthy controls), in conjunction
      with a Markov random field regularization that ensures mutual consistency of the
      regional learning among partially overlapping image blocks. The decomposition is
      performed in a principled way so that the normal part fits well with the learned
      normative model, while the residual term absorbs pathological patterns, which may
      then be detected through a statistical significance test. The decomposition is
      applied to multiple image features from an individual scan, detecting
      abnormalities using both intensity and shape information. We form an iterative
      scheme that interleaves abnormality detection with deformable registration,
      gradually improving robustness of the spatial normalization and precision of the
      detection. The algorithm is evaluated with simulated images and clinical data of
      brain lesions, and is shown to achieve robust deformable registration and
      localize pathological regions simultaneously. The algorithm is also applied on
      images from Alzheimer's disease patients to demonstrate the generality of the
      method.

PMID- 27046848
TI  - On the Quantitative Potential of Viscoelastic Response (VisR) Ultrasound Using
      the One-Dimensional Mass-Spring-Damper Model.
AB  - Viscoelastic response (VisR) ultrasound is an acoustic radiation force (ARF)
      based imaging method that fits induced displacements to a one-dimensional (1-D)
      mass-spring-damper (MSD) model to estimate the ratio of viscous to elastic
      moduli, tau, in viscoelastic materials. Error in VisR tau estimation arises from
      inertia and acoustic displacement underestimation. These error sources are herein
      evaluated using finite-element method (FEM) simulations, error correction methods
      are developed, and corrected VisR tau estimates are compared with true simulated
      tau values to assess VisR's relevance to quantifying viscoelasticity. With regard
      to inertia, adding a mass term in series with the Voigt model, to achieve the MSD
      model, accounts for inertia due to tissue mass when ideal point force excitations
      are used. However, when volumetric ARF excitations are applied, the induced
      complex system inertia is not described by the single-degree-of-freedom MSD
      model, causing VisR to overestimate tau. Regarding acoustic displacement
      underestimation, associated deformation of ARF-induced displacement profiles
      further distorts VisR tau estimates. However, median error in VisR tau is reduced
      to approximately -10% using empirically derived error correction functions
      applied to simulated viscoelastic materials with viscous and elastic properties
      representative of tissue. The feasibility of corrected VisR imaging is then
      demonstrated in vivo in the rectus femoris muscle of an adult with no known
      neuromuscular disorders. These results suggest VisR's potential relevance to
      quantifying viscoelastic properties clinically.

PMID- 27046849
TI  - Modeling, Measuring, and Compensating Color Weak Vision.
AB  - We use methods from Riemann geometry to investigate transformations between the
      color spaces of color-normal and color-weak observers. The two main applications
      are the simulation of the perception of a color weak observer for a color-normal
      observer, and the compensation of color images in a way that a color-weak
      observer has approximately the same perception as a color-normal observer. The
      metrics in the color spaces of interest are characterized with the help of
      ellipsoids defined by the just-noticeable-differences between the colors which
      are measured with the help of color-matching experiments. The constructed
      mappings are the isometries of Riemann spaces that preserve the perceived color
      differences for both observers. Among the two approaches to build such an
      isometry, we introduce normal coordinates in Riemann spaces as a tool to
      construct a global color-weak compensation map. Compared with the previously used
      methods, this method is free from approximation errors due to local
      linearizations, and it avoids the problem of shifting locations of the origin of
      the local coordinate system. We analyze the variations of the Riemann metrics for
      different observers obtained from new color-matching experiments and describe
      three variations of the basic method. The performance of the methods is evaluated
      with the help of semantic differential tests.

PMID- 27046850
TI  - Modeling Non-Stationary Asymmetric Lens  Blur by Normal Sinh-Arcsinh Model.
AB  - Images acquired by a camera show lens blur due to imperfection in the optical
      system even when images are properly focused. Lens blur is non-stationary in a
      sense that the amount of blur depends on pixel locations in a sensor. Lens blur
      is also asymmetric in a sense that the amount of blur is different in the radial
      and tangential directions, and also in the inward and outward radial directions.
      This paper presents parametric blur kernel models based on the normal sinh
      arcsinh distribution function. The proposed models can provide flexible shapes of
      blur kernels with a different symmetry and skewness to model complicated lens
      blur due to optical aberration in a properly focused images accurately. Blur of
      single focal length lenses is estimated, and the accuracy of the models is
      compared with the existing parametric blur models. An advantage of the proposed
      models is demonstrated through deblurring experiments.

PMID- 27046851
TI  - A Spatially Focused Method for High Density Electrode-Based Functional Brain
      Mapping Applications.
AB  - Mapping the electric field of the brain with electrodes benefits from its
      superior temporal resolution but is prone to low spatial resolution property
      comparing with other modalities such as fMRI, which can directly impact the
      precision of clinical diagnosis. Simulations show that dense arrays with
      straightforwardly miniaturized electrodes in terms of size and pitch may not
      improve the spatial resolution but only strengthen the cross coupling between
      adjacent channels due to volume conduction. We present a new spatially focused
      method to improve the electrode spatial selectivity and consequently suppress the
      neural signal coupling from the sources in the vicinity. Compared with existing
      spatial filtering methods with fixed coefficients, the proposed method is
      adaptively optimized for the geometric parameters of the recording electrode
      arrays, including electrode size, pitch and source depth. The effective spatial
      bandwidth, characterized as Radius of Half Power, can be reduced by about 70% for
      ECoG and the case of distant sources scenarios. The proposed method has been
      applied to the analysis of high-frequency oscillations (HFOs) in seizures to
      study the ictal pathway in the epileptogenic region. The results reveal lucid HFO
      wavefront propagation in both preictal and ictal stages due to a 75% reduction in
      the coupling effect. The results also show that a specific power threshold of
      preictal HFOs is needed in order to initiate an epileptic seizure. This
      demonstrates that our method indeed facilitates the investigation of complex
      neurobiological signals preprocessing applications.

PMID- 27046852
TI  - Frequency Analysis and Feature Reduction Method for Prediction of Cerebral Palsy
      in Young Infants.
AB  - The aim of this paper is to achieve a model for prediction of cerebral palsy
      based on motion data of young infants. The prediction is formulated as a
      classification problem to assign each of the infants to one of the healthy or
      with cerebral palsy groups. Unlike formerly proposed features that are mostly
      defined in the time domain, this study proposes a set of features derived from
      frequency analysis of infants' motions. Since cerebral palsy affects the
      variability of the motions, and frequency analysis is an intuitive way of
      studying variability, suggested features are suitable and consistent with the
      nature of the condition. In the current application, a well-known problem, few
      subjects and many features, was initially encountered. In such a case, most
      classifiers get trapped in a suboptimal model and, consequently, fail to provide
      sufficient prediction accuracy. To solve this problem, a feature selection method
      that determines features with significant predictive ability is proposed. The
      feature selection method decreases the risk of false discovery and, therefore,
      the prediction model is more likely to be valid and generalizable for future use.
      A detailed study is performed on the proposed features and the feature selection
      method: the classification results confirm their applicability. Achieved
      sensitivity of 86%, specificity of 92% and accuracy of 91% are comparable with
      state-of-the-art clinical and expert-based methods for predicting cerebral palsy.

PMID- 27046853
TI  - Dual Low-Rank Pursuit: Learning Salient Features for Saliency Detection.
AB  - Saliency detection is an important procedure for machines to understand visual
      world as humans do. In this paper, we consider a specific saliency detection
      problem of predicting human eye fixations when they freely view natural images,
      and propose a novel dual low-rank pursuit (DLRP) method. DLRP learns saliency
      aware feature transformations by utilizing available supervision information and
      constructs discriminative bases for effectively detecting human fixation points
      under the popular low-rank and sparsity-pursuit framework. Benefiting from the
      embedded high-level information in the supervised learning process, DLRP is able
      to predict fixations accurately without performing the expensive object
      segmentation as in the previous works. Comprehensive experiments clearly show the
      superiority of the proposed DLRP method over the established state-of-the-art
      methods. We also empirically demonstrate that DLRP provides stronger
      generalization performance across different data sets and inherits the advantages
      of both the bottom-up- and top-down-based saliency detection methods.

PMID- 27046857
TI  - An Efficient Fine-to-Coarse Wayfinding Strategy for Robot Navigation in
      Regionalized Environments.
AB  - This paper proposes an efficient wayfinding strategy for robot navigation in
      regionalized environments by designing a regionalized spatial knowledge model
      (RSK model) and a region-based wayfinding algorithm, i.e., a fine-to-coarse A*
      (FTC-A*) search algorithm. First, the RSK model, which imitates the
      representation of environments in the human brain, is presented to describe the
      search environments. The environments that are divided into regions are
      represented by a hierarchical nested structure where small regions are grouped
      together to form superordinate regions. Second, on the basis of the RSK model, an
      FTC-A* search algorithm is developed to plan the fine-to-coarse route. By making
      a fine planning to robot surroundings in vicinity, but a coarse planning to that
      at the distance, the FTC-A* algorithm can effectively reduce computational
      complexity, so as to enhance the efficiency of route search, and meanwhile makes
      robots to react quickly to user's commands, especially in large-scale
      environments. Finally, four exhaustive simulations and a physical experiment have
      been carried out to illustrate the feasibility and effectiveness of the proposed
      wayfinding strategy.

PMID- 27046858
TI  - Weakly Supervised Multilabel Clustering and its Applications in Computer Vision.
AB  - Clustering is a useful statistical tool in computer vision and machine learning.
      It is generally accepted that introducing supervised information brings
      remarkable performance improvement to clustering. However, assigning accurate
      labels is expensive when the amount of training data is huge. Existing supervised
      clustering methods handle this problem by transferring the bag-level labels into
      the instance-level descriptors. However, the assumption that each bag has a
      single label limits the application scope seriously. In this paper, we propose
      weakly supervised multilabel clustering, which allows assigning multiple labels
      to a bag. Based on this, the instance-level descriptors can be clustered with the
      guidance of bag-level labels. The key technique is a weakly supervised random
      forest that infers the model parameters. Thereby, a deterministic annealing
      strategy is developed to optimize the nonconvex objective function. The proposed
      algorithm is efficient in both the training and the testing stages. We apply it
      to three popular computer vision tasks: 1) image clustering; 2) semantic image
      segmentation; and 3) multiple objects localization. Impressive performance on the
      state-of-the-art image data sets is achieved in our experiments.

PMID- 27046859
TI  - Cross-Modal Retrieval With CNN Visual Features: A New Baseline.
AB  - Recently, convolutional neural network (CNN) visual features have demonstrated
      their powerful ability as a universal representation for various recognition
      tasks. In this paper, cross-modal retrieval with CNN visual features is
      implemented with several classic methods. Specifically, off-the-shelf CNN visual
      features are extracted from the CNN model, which is pretrained on ImageNet with
      more than one million images from 1000 object categories, as a generic image
      representation to tackle cross-modal retrieval. To further enhance the
      representational ability of CNN visual features, based on the pretrained CNN
      model on ImageNet, a fine-tuning step is performed by using the open source Caffe
      CNN library for each target data set. Besides, we propose a deep semantic
      matching method to address the cross-modal retrieval problem with respect to
      samples which are annotated with one or multiple labels. Extensive experiments on
      five popular publicly available data sets well demonstrate the superiority of CNN
      visual features for cross-modal retrieval.

PMID- 27046864
TI  - Erratum to "On Feature Motion Decorrelation in Ultrasound Speckle Tracking".

PMID- 27046865
TI  - Neural Data-Driven Musculoskeletal Modeling for Personalized Neurorehabilitation
      Technologies.
AB  - OBJECTIVES: The development of neurorehabilitation technologies requires the
      profound understanding of the mechanisms underlying an individual's motor ability
      and impairment. A major factor limiting this understanding is the difficulty of
      bridging between events taking place at the neurophysiologic level (i.e., motor
      neuron firings) with those emerging at the musculoskeletal level (i.e. joint
      actuation), in vivo in the intact moving human. This review presents emerging
      model-based methodologies for filling this gap that are promising for developing
      clinically viable technologies. METHODS: We provide a design overview of
      musculoskeletal modeling formulations driven by recordings of neuromuscular
      activity with a critical comparison to alternative model-free approaches in the
      context of neurorehabilitation technologies. We present advanced electromyography
      based techniques for interfacing with the human nervous system and model-based
      techniques for translating the extracted neural information into estimates of
      motor function. RESULTS: We introduce representative application areas where
      modeling is relevant for accessing neuromuscular variables that could not be
      measured experimentally. We then show how these variables are used for designing
      personalized rehabilitation interventions, biologically inspired limbs, and human
      machine interfaces. CONCLUSION: The ability of using electrophysiological
      recordings to inform biomechanical models enables accessing a broader range of
      neuromechanical variables than analyzing electrophysiological data or movement
      data individually. This enables understanding the neuromechanical interplay
      underlying in vivo movement function, pathology, and robot-assisted motor
      recovery. SIGNIFICANCE: Filling the gap between our understandings of movement
      neural and mechanical functions is central for addressing one of the major
      challenges in neurorehabilitation: personalizing current technologies and
      interventions to an individual's anatomy and impairment.

PMID- 27046866
TI  - Decoding Upper Limb Movement Attempt From EEG Measurements of the Contralesional
      Motor Cortex in Chronic Stroke Patients.
AB  - GOAL: Stroke survivors usually require motor rehabilitation therapy as, due to
      the lesion, they completely or partially loss mobility in the limbs. Brain
      computer interface technology offers the possibility of decoding the attempt to
      move paretic limbs in real time to improve existing motor rehabilitation.
      However, a major difficulty for the practical application of the BCI to stroke
      survivors is that the brain rhythms that encode the motor states might be
      diminished due to the lesion. This study investigates the continuous decoding of
      natural attempt to move the paralyzed upper limb in stroke survivors from
      electroencephalographic signals of the unaffected contralesional motor cortex.
      RESULTS: Experiments were carried out with the aid of six severely affected
      chronic stroke patients performing/attempting self-selected reaching movements of
      the unaffected/affected upper limb. The electroencephalographic (EEG) analysis
      showed significant cortical activation on the uninjured motor cortex when moving
      the contralateral unaffected arm and in the attempt to move the ipsilateral
      affected arm. Using this activity, significant continuous decoding of movement
      was obtained in six out of six participants in movements of the unaffected limb,
      and in four out of six participants in the attempt to move the affected limb.
      CONCLUSION: This study showed that it is possible to construct a decoder of the
      attempt to move the paretic arm for chronic stroke patients using the EEG
      activity of the healthy contralesional motor cortex. SIGNIFICANCE: This decoding
      model could provide to stroke survivors with a natural, easy, and intuitive way
      to achieve control of BCIs or robot-assisted rehabilitation devices.

PMID- 27046867
TI  - Hierarchical Maximum Likelihood Clustering Approach.
AB  - OBJECTIVE: In this paper, we focused on developing a clustering approach for
      biological data. In many biological analyses, such as multiomics data analysis
      and genome-wide association studies analysis, it is crucial to find groups of
      data belonging to subtypes of diseases or tumors. METHODS: Conventionally, the k
      means clustering algorithm is overwhelmingly applied in many areas including
      biological sciences. There are, however, several alternative clustering
      algorithms that can be applied, including support vector clustering. In this
      paper, taking into consideration the nature of biological data, we propose a
      maximum likelihood clustering scheme based on a hierarchical framework. RESULTS:
      This method can perform clustering even when the data belonging to different
      groups overlap. It can also perform clustering when the number of samples is
      lower than the data dimensionality. CONCLUSION: The proposed scheme is free from
      selecting initial settings to begin the search process. In addition, it does not
      require the computation of the first and second derivative of likelihood
      functions, as is required by many other maximum likelihood-based methods.
      SIGNIFICANCE: This algorithm uses distribution and centroid information to
      cluster a sample and was applied to biological data. A MATLAB implementation of
      this method can be downloaded from the web link
      http://www.riken.jp/en/research/labs/ims/med_sci_math/.

PMID- 27046868
TI  - PSQP: Puzzle Solving by Quadratic Programming.
AB  - In this article we present the first effective method based on global
      optimization for the reconstruction of image puzzles comprising rectangle pieces
      Puzzle Solving by Quadratic Programming (PSQP). The proposed novel mathematical
      formulation reduces the problem to the maximization of a constrained quadratic
      function, which is solved via a gradient ascent approach. The proposed method is
      deterministic and can deal with arbitrary identical rectangular pieces. We
      provide experimental results showing its effectiveness when compared to state-of
      the-art approaches. Although the method was developed to solve image puzzles, we
      also show how to apply it to the reconstruction of simulated strip-shredded
      documents, broadening its applicability.

PMID- 27046869
TI  - Segmenting Retinal Blood Vessels With Deep Neural Networks.
AB  - The condition of the vascular network of human eye is an important diagnostic
      factor in ophthalmology. Its segmentation in fundus imaging is a nontrivial task
      due to variable size of vessels, relatively low contrast, and potential presence
      of pathologies like microaneurysms and hemorrhages. Many algorithms, both
      unsupervised and supervised, have been proposed for this purpose in the past. We
      propose a supervised segmentation technique that uses a deep neural network
      trained on a large (up to 400[Formula: see text]000) sample of examples
      preprocessed with global contrast normalization, zero-phase whitening, and
      augmented using geometric transformations and gamma corrections. Several variants
      of the method are considered, including structured prediction, where a network
      classifies multiple pixels simultaneously. When applied to standard benchmarks of
      fundus imaging, the DRIVE, STARE, and CHASE databases, the networks significantly
      outperform the previous algorithms on the area under ROC curve measure (up to >
      0.99) and accuracy of classification (up to > 0.97 ). The method is also
      resistant to the phenomenon of central vessel reflex, sensitive in detection of
      fine vessels ( sensitivity > 0.87 ), and fares well on pathological cases.

PMID- 27046870
TI  - Fast Computation of Wideband Beam Pattern for Designing Large-Scale 2-D Arrays.
AB  - For real-time and high-resolution 3-D ultrasound imaging, the design of sparse
      distribution and weights of elements of a large-scale wideband 2-D array is
      needed to reduce hardware cost and achieve better directivity. However, due to
      the high time consumption of computing the wideband beam pattern, the design
      methods that need massive iterations have rarely been applied to design large
      scale wideband 2-D arrays by directly computing the wideband beam pattern. In
      this paper, a fast method is proposed to realize the computation of a wideband
      beam pattern of arbitrary 2-D arrays in the far field in order to design large
      scale wideband 2-D arrays. The proposed fast method exploits two important
      techniques: 1) nonuniform fast Fourier transform (FFT) and 2) short inverse FFT.
      Compared with the commonly used ultrasound simulator Field II, two orders of
      magnitude improvement in computation speed is achieved with comparable accuracy.
      The proposed fast method enables massive iterations of direct wideband beam
      pattern computation of arbitrary large-scale 2-D arrays. A design example in this
      paper demonstrates that the proposed fast method can help achieve better
      performance in designing large-scale wideband 2-D arrays.

PMID- 27046871
TI  - Structure Function Estimated From Histological Tissue Sections.
AB  - Ultrasonic scattering is determined by not only the properties of individual
      scatterers but also the correlation among scatterer positions. The role of
      scatterer spatial correlation is significant for dense medium, but has not been
      fully understood. The effect of scatterer spatial correlation may be modeled by
      the structure function as a frequency-dependent factor in the backscatter
      coefficient (BSC) expression. The structure function has been previously
      estimated from the BSC data. The aim of this study is to estimate the structure
      function from histology to test if the acoustically estimated structure function
      is indeed caused by the scatterer spatial distribution. Hematoxylin and eosin
      stained histological sections from dense cell pellet biophantoms were digitized.
      The scatterer positions were determined manually from the histological images.
      The structure function was calculated from the extracted scatterer positions. The
      structure function obtained from histology showed reasonable agreement in the
      shape but not in the amplitude, compared with the structure function previously
      estimated from the backscattered data. Fitting a polydisperse structure function
      model to the histologically estimated structure function yielded relatively
      accurate cell radius estimates ([Formula: see text]). Furthermore, two types of
      mouse tumors that have similar cell size and shape but distinct cell spatial
      distributions were studied, where the backscattered data were shown to be related
      to the cell spatial distribution through the structure function estimated from
      histology. In conclusion, the agreement between acoustically estimated and
      histologically estimated structure functions suggests that the acoustically
      estimated structure function is related to the scatterer spatial distribution.

PMID- 27046873
TI  - A Novel Image Quality Assessment With Globally and Locally Consilient Visual
      Quality Perception.
AB  - Computational models for image quality assessment (IQA) have been developed by
      exploring effective features that are consistent with the characteristics of a
      human visual system (HVS) for visual quality perception. In this paper, we first
      reveal that many existing features used in computational IQA methods can hardly
      characterize visual quality perception for local image characteristics and
      various distortion types. To solve this problem, we propose a new IQA method,
      called the structural contrast-quality index (SC-QI), by adopting a structural
      contrast index (SCI), which can well characterize local and global visual quality
      perceptions for various image characteristics with structural-distortion types.
      In addition to SCI, we devise some other perceptually important features for our
      SC-QI that can effectively reflect the characteristics of HVS for contrast
      sensitivity and chrominance component variation. Furthermore, we develop a
      modified SC-QI, called structural contrast distortion metric (SC-DM), which
      inherits desirable mathematical properties of valid distance metricability and
      quasi-convexity. So, it can effectively be used as a distance metric for image
      quality optimization problems. Extensive experimental results show that both SC
      QI and SC-DM can very well characterize the HVS's properties of visual quality
      perception for local image characteristics and various distortion types, which is
      a distinctive merit of our methods compared with other IQA methods. As a result,
      both SC-QI and SC-DM have better performances with a strong consilience of global
      and local visual quality perception as well as with much lower computation
      complexity, compared with the state-of-the-art IQA methods. The MATLAB source
      codes of the proposed SC-QI and SC-DM are publicly available online at
      https://sites.google.com/site/sunghobaecv/iqa.

PMID- 27046872
TI  - Analysis of Coherent and Diffuse Scattering Using a Reference Phantom.
AB  - The estimation of many spectral-based quantitative ultrasound parameters assumes
      that backscattered echo signals are from a stationary, incoherent scattering
      process. The accuracy of these assumptions in real tissue can limit the
      diagnostic value of these parameters and the physical insight about tissue
      microstructure they can convey. This work presents an empirical decision test to
      determine the presence of significant coherent contributions to echo signals and
      whether they are caused by low scatterer number densities or the presence of
      specular reflectors or scatterers with periodic spacing. This is achieved by
      computing parameters from echo signals that quantify stationary or nonstationary
      features related to coherent scattering, and then comparing their values to
      thresholds determined from a reference material providing diffuse scattering. The
      paper first presents a number of parameters with demonstrated sensitivity to
      coherent scattering and describes criteria to select those with the highest
      sensitivity using simulated and phantom-based echo data. Results showed that the
      echo amplitude signal-to-noise ratio and the multitaper-generalized spectrum were
      the parameters with the highest sensitivity to coherent scattering with
      stationary and nonstationary features, respectively. These parameters were
      incorporated into the reference-based decision test, which successfully
      identified regions in simulated and tissue-mimicking phantoms with different
      incoherent and coherent scattering conditions. When scatterers with periodic
      organization were detected, the combination of stationary and nonstationary
      analysis permitted the estimation of the mean spacing below and above the
      resolution limit imposed by the pulse size. Preliminary applications of this
      algorithm to human cervical tissue ex vivo showed correspondence between regions
      of B-mode images showing bright reflectors, tissue interfaces, and hypoechoic
      regions with regions classified as specular reflectors and low scatterer number
      density. These results encourage further application of the algorithm to more
      structurally complex phantoms and tissue.

PMID- 27046874
TI  - Direct Fourier Inversion Reconstruction Algorithm for Computed Laminography.
AB  - Synchrotron radiation computed laminography (CL) was developed to complement the
      conventional computed tomography as a non-destructive 3D imaging method for the
      inspection of flat thin objects. Recent progress in hardware at synchrotron
      sources allows one to record internal evolution of specimens at the micrometer
      scale and sub-second range but also requires increased reconstruction speed to
      follow structural changes online. A 3D image of the sample interior is usually
      reconstructed by the well-established filtered backprojection (FBP) approach.
      Despite of a great success in the reduction of reconstruction time via parallel
      computations, the FBP algorithm still remains a time-consuming procedure. A
      promising way to significantly shorten computation time is to directly perform
      backprojection in frequency domain (a direct Fourier inversion approach). The
      corresponding algorithms are rarely considered in the literature because of a
      poor performance or inferior reconstruction quality resulted from inaccurate
      interpolation in Fourier domain. In this paper, we derive a Fourier-based
      reconstruction equation designed for the CL scanning geometry. Furthermore, we
      outline the translation of the continuous solution to a discrete version, which
      utilizes 3D sinc interpolation. A projection resampling technique allowing for
      the reduction of the expensive interpolation to its 1D version is proposed. A
      series of numerical experiments confirms that the resulting image quality is well
      comparable with the FBP approach while reconstruction time is drastically
      reduced.

PMID- 27046875
TI  - Joint Low-Rank and Sparse Principal Feature Coding for Enhanced Robust
      Representation and Visual Classification.
AB  - Recovering low-rank and sparse subspaces jointly for enhanced robust
      representation and classification is discussed. Technically, we first propose a
      transductive low-rank and sparse principal feature coding (LSPFC) formulation
      that decomposes given data into a component part that encodes low-rank sparse
      principal features and a noise-fitting error part. To well handle the outside
      data, we then present an inductive LSPFC (I-LSPFC). I-LSPFC incorporates embedded
      low-rank and sparse principal features by a projection into one problem for
      direct minimization, so that the projection can effectively map both inside and
      outside data into the underlying subspaces to learn more powerful and informative
      features for representation. To ensure that the learned features by I-LSPFC are
      optimal for classification, we further combine the classification error with the
      feature coding error to form a unified model, discriminative LSPFC (D-LSPFC), to
      boost performance. The model of D-LSPFC seamlessly integrates feature coding and
      discriminative classification, so the representation and classification powers
      can be enhanced. The proposed approaches are more general, and several recent
      existing low-rank or sparse coding algorithms can be embedded into our problems
      as special cases. Visual and numerical results demonstrate the effectiveness of
      our methods for representation and classification.

PMID- 27046876
TI  - A Kernel Density Estimator-Based Maximum  A Posteriori Image Reconstruction
      Method for  Dynamic Emission Tomography Imaging.
AB  - A novel maximum a posteriori (MAP) method for dynamic single-photon emission
      computed tomography image reconstruction is proposed. The prior probability is
      modeled as a multivariate kernel density estimator (KDE), effectively modeling
      the prior probability non-parametrically, with the aim of reducing the effects of
      artifacts arising from inconsistencies in projection measurements in low-count
      regimes where projections are dominated by noise. The proposed prior spatially
      and temporally limits the variation of time-activity functions (TAFs) and
      attracts similar TAFs together. The similarity between TAFs is determined by the
      spatial and range scaling parameters of the KDE-like prior. The resulting
      iterative image reconstruction method is evaluated using two simulated phantoms,
      namely the extended cardiac-torso (XCAT) heart phantom and a simulated Mini
      Deluxe Phantom. The phantoms were chosen to observe the effects of the proposed
      prior on the TAFs based on the vicinity and abutments of regions with different
      activities. Our results show the effectiveness of the proposed iterative
      reconstruction method, especially in low-count regimes, which provides better
      uniformity within each region of activity, significant reduction of
      spatiotemporal variations caused by noise, and sharper separation between
      different regions of activity than expectation maximization and an MAP method
      employing a more traditional Gibbs prior.

PMID- 27046877
TI  - A Trunk Support System to Identify Posture Control Mechanisms in Populations
      Lacking Independent Sitting.
AB  - Populations with moderate-to-severe motor control impairments often exhibit
      degraded trunk control and/or lack the ability to sit unassisted. These
      populations need more research, yet their underdeveloped trunk control
      complicates identification of neural mechanisms behind their movements. The
      purpose of this study was to overcome this barrier by developing the first multi
      articulated trunk support system to identify visual, vestibular, and
      proprioception contributions to posture in populations lacking independent
      sitting. The system provided external stability at a user-specific level on the
      trunk, so that body segments above the level of support required active posture
      control. The system included a tilting surface (controlled via servomotor) as a
      stimulus to investigate sensory contributions to postural responses. Frequency
      response and coherence functions between the surface tilt and trunk support were
      used to characterize system dynamics and indicated that surface tilts were
      accurately transmitted up to 5 Hz. Feasibility of collecting kinematic data in
      participants lacking independent sitting was demonstrated in two populations: two
      typically developing infants, [Formula: see text] months, in a longitudinal study
      (eight sessions each) and four children with moderate-to-severe cerebral palsy
      (GMFCS III-V). Adaptability in the system was assessed by testing 16 adults (ages
      18-63). Kinematic responses to continuous pseudorandom surface tilts were
      evaluated across 0.046-2 Hz and qualitative feedback indicated that the trunk
      support and stimulus were comfortable for all subjects. Concepts underlying the
      system enable both research for, and rehabilitation in, populations lacking
      independent sitting.

PMID- 27046878
TI  - Investigating Glioblastoma Angiogenesis Using A 3D in Vitro GelMA Microwell
      Platform.
AB  - Angiogenesis is an indispensable mechanism in physiological and pathological
      development of tumors that requires an adequate blood supply. Therefore,
      understanding the angiogenesis mechanism of tumors has become an important
      research area to develop reliable and effective therapies for the treatment of
      tumors. Although several in vivo and in vitro models were developed and used to
      study the underlying mechanism of angiogenesis, they showed limited success.
      Therefore, there is an urgent need to build a stable and cost-effective three
      dimensional (3D) in vitro angiogenesis model to investigate the tumor formation.
      In this study, we designed a 3D in vitro angiogenesis model based on gelatin
      methacrylate (GelMA) hydrogel microwells to mimic an in vivo-like
      microenvironment for co-cultured glioblastoma and endothelial cells. Our results
      confirmed the in vitro formation of microtubules during the angiogenic process.
      We believe that our cost-effective platform can be used for the high-throughput
      screening of anti-angiogenesis drugs and even for the development of better
      treatment strategies.

PMID- 27046879
TI  - A Novel Electrical Model for Advection-Diffusion-Based Molecular Communication in
      Nanonetworks.
AB  - In this paper, we propose an end-to-end electrical model to characterize the
      communication between two nanomachines via advection-diffusion motion along the
      conventional pipe medium. For this modeling, we consider three modules consisting
      of transmitter, advection-diffusion propagation and receiver. The modulation
      scheme and releasing molecules through the conventional pipe medium from the
      transmitter nanomachine is represented in the transmitter module. The advection
      diffusion propagation of molecules along the flow-induced path is shown in
      advection-diffusion propagation module, and the demodulation scheme of bounded
      particles at the receiver nanomachine is characterized in the receiver module.
      Our objective is to find an electrical model of each module under the zero
      initial condition which enables us to represent the electrical circuit related to
      each module. The transmitter and the signal propagation models are built on the
      basis of the molecular advection-diffusion physics, whereas the receiver model is
      interpreted by stemming from the theory of the ligand-receptor binding chemical
      process. In addition, we employ the transfer function of modules to derive the
      normalized gain and the delay of each module. Supported by numerical results, we
      analyze the effect of physical parameters of the pipe medium on the total
      normalized gain and delay of molecular communications.

PMID- 27046880
TI  - A High-Voltage-Tolerant and Precise Charge-Balanced Neuro-Stimulator in Low
      Voltage CMOS Process.
AB  - This paper presents a 4 * VDD neuro-stimulator in a 0.18- MUm 1.8 V/3.3 V CMOS
      process. The self-adaption bias technique and stacked MOS configuration are used
      to prevent transistors from the electrical overstress and gate-oxide reliability
      issue. A high-voltage-tolerant level shifter with power-on protection is used to
      drive the neuro-stimulator The reliability measurement of up to 100 million
      periodic cycles with 3000- MUA biphasic stimulations in 12-V power supply has
      verified that the proposed neuro-stimulator is robust. Precise charge balance is
      achieved by using a novel current memory cell with the dual calibration loops and
      leakage current compensation. The charge mismatch is down to 0.25% over all the
      stimulus current ranges (200-300 MUA) The residual average dc current is less
      than 6.6 nA after shorting operation.

PMID- 27046881
TI  - CONE: Convex-Optimized-Synaptic Efficacies for Temporally Precise Spike Mapping.
AB  - Spiking neural networks are well suited to perform time-dependent pattern
      recognition problems by encoding the temporal dimension in precise spike times.
      With an appropriate set of weights, a spiking neuron can emit precisely timed
      action potentials in response to spatiotemporal input spikes. However, deriving
      supervised learning rules for spike mapping is nontrivial due to the increased
      complexity. Existing methods rely on heuristic approaches that do not guarantee a
      convex objective function and, therefore, may not converge to a global minimum.
      In this paper, we present a novel technique to obtain the weights of spiking
      neurons by formulating the problem in a convex optimization framework, rendering
      it be compatible with the established methods. We introduce techniques to
      influence the weight distribution and membrane trajectory, and then study how
      these factors affect robustness in the presence of noise. In addition, we show
      how the existence of a solution can be determined and assess memory capacity
      limits of a neuron model using synthetic examples. The practical utility of our
      technique is further assessed by its application to gait-event detection using
      the experimental data.

PMID- 27046882
TI  - Multiple ECG Fiducial Points-Based Random Binary Sequence Generation for Securing
      Wireless Body Area Networks.
AB  - Generating random binary sequences (BSes) is a fundamental requirement in
      cryptography. A BS is a sequence of N bits, and each bit has a value of 0 or 1.
      For securing sensors within wireless body area networks (WBANs),
      electrocardiogram (ECG)-based BS generation methods have been widely investigated
      in which interpulse intervals (IPIs) from each heartbeat cycle are processed to
      produce BSes. Using these IPI-based methods to generate a 128-bit BS in real time
      normally takes around half a minute. In order to improve the time efficiency of
      such methods, this paper presents an ECG multiple fiducial-points based binary
      sequence generation (MFBSG) algorithm. The technique of discrete wavelet
      transforms is employed to detect arrival time of these fiducial points, such as
      P, Q, R, S, and T peaks. Time intervals between them, including RR, RQ, RS, RP,
      and RT intervals, are then calculated based on this arrival time, and are used as
      ECG features to generate random BSes with low latency. According to our analysis
      on real ECG data, these ECG feature values exhibit the property of randomness
      and, thus, can be utilized to generate random BSes. Compared with the schemes
      that solely rely on IPIs to generate BSes, this MFBSG algorithm uses five feature
      values from one heart beat cycle, and can be up to five times faster than the
      solely IPI-based methods. So, it achieves a design goal of low latency. According
      to our analysis, the complexity of the algorithm is comparable to that of fast
      Fourier transforms. These randomly generated ECG BSes can be used as security
      keys for encryption or authentication in a WBAN system.

PMID- 27046883
TI  - A Double-Partial Least-Squares Model for the Detection of Steady-State Visual
      Evoked Potentials.
AB  - Establishing a high-accuracy and training-free brain-computer interface (BCI)
      system is essential for improving BCI practicality. In this study, we propose for
      the first time a training-free double-partial least-squares (D-PLS) model for
      steady-state visual evoked potential (SSVEP) detection that consists of double
      layer PLS, a PLS spatial filter, and a PLS feature extractor.
      Electroencephalographic data from 11 healthy volunteers under four different
      visual stimulation frequencies were used to test the proposed method. Compared
      with commonly used spatial filters, minimum energy combination and average
      maximum contrast combination, the classification accuracies could be improved 2
      10% by our proposed PLS spatial filter. Furthermore, our proposed PLS feature
      extractor achieved better performance than current feature extraction methods,
      namely power spectral density analysis, canonical correlation analysis, and the
      use of the least absolute shrinkage and selection operator. The average
      classification accuracy for our proposed D-PLS model exceeded [Formula: see text]
      when the signal time window was longer than 3.5 s and reached as high as
      [Formula: see text] when the time window was 5 s. Moreover, the D-PLS model can
      be easily set without training data, so it can be used widely in SSVEP-based BCI
      systems.

PMID- 27046884
TI  - Sparse Support Vector Machine for Intrapartum Fetal Heart Rate Classification.
AB  - Fetal heart rate (FHR) monitoring is routinely used in clinical practice to help
      obstetricians assess fetal health status during delivery. However, early
      detection of fetal acidosis that allows relevant decisions for operative delivery
      remains a challenging task, receiving considerable attention. This contribution
      promotes sparse support vector machine classification that permits to select a
      small number of relevant features and to achieve efficient fetal acidosis
      detection. A comprehensive set of features is used for FHR description, including
      enhanced and computerized clinical features, frequency domain, and scaling and
      multifractal features, all computed on a large (1288 subjects) and well
      documented database. The individual performance obtained for each feature
      independently is discussed first. Then, it is shown that the automatic selection
      of a sparse subset of features achieves satisfactory classification performance
      (sensitivity 0.73 and specificity 0.75, outperforming clinical practice). The
      subset of selected features (average depth of decelerations MADdtrd, baseline
      level beta0 , and variability H) receives simple interpretation in clinical
      practice. Intrapartum fetal acidosis detection is improved in several respects: A
      comprehensive set of features combining clinical, spectral, and scale-free
      dynamics is used; an original multivariate classification targeting both sparse
      feature selection and high performance is devised; state-of-the-art performance
      is obtained on a much larger database than that generally studied with
      description of common pitfalls in supervised classification performance
      assessments.

PMID- 27046885
TI  - State Estimation of Discrete-Time Switched Neural Networks With Multiple
      Communication Channels.
AB  - In this paper, the state estimation problem for a class of discrete-time switched
      neural networks with modal persistent dwell time (MPDT) switching and mixed time
      delays is investigated. The considered switching law, not only generalizes the
      commonly studied dwell-time (DT) and average DT (ADT) switchings, but also
      further attaches mode-dependency to the persistent DT (PDT) switching that is
      shown to be more general. Multiple communication channels, which include one
      primary channel and multiredundant channels, are considered to coexist for the
      state estimation of underlying switched neural networks. The desired mode
      dependent filters are designed such that the resulting filtering error system is
      exponentially mean-square stable with a guaranteed nonweighted generalized H2
      performance index. It is verified that better filtering performance index can be
      achieved as the number of channels to be used increases. The potential and
      effectiveness of the developed theoretical results are demonstrated via a
      numerical example.

PMID- 27046886
TI  - Efficient Markov Blanket Discovery and Its Application.
AB  - In a Bayesian network (BN), a target node is independent of all other nodes given
      its Markov blanket (MB), and finding the MB has many applications, including
      feature selection and BN structure learning. We propose a new MB discovery
      algorithm, simultaneous MB (STMB), to improve the efficiency of the existing
      topology-based MB discovery algorithms. The proposed method removes the necessity
      of enforcing the symmetry constraint that is prevalent in existing algorithms, by
      exploiting the coexisting property between spouses and descendants of the target
      node. Since STMB mainly reduces the number of independence tests needed to
      complete the MB set after finding the parents-and-children set, it is applicable
      to all previous topology-based methods. STMB is both sound and complete.
      Experiments show that STMB has a comparable accuracy but much better efficiency
      than state-of-the-art methods. An application on benchmark feature selection
      datasets further demonstrates the excellent performance of STMB.

PMID- 27046887
TI  - A 3-D Active Contour Method for Automated Segmentation of the Left Ventricle From
      Magnetic Resonance Images.
AB  - OBJECTIVE: This study's objective is to develop and validate a fast automated 3-D
      segmentation method for cardiac magnetic resonance imaging (MRI). The
      segmentation algorithm automatically reconstructs cardiac MRI DICOM data into a 3
      D model (i.e., direct volumetric segmentation), without relying on prior
      statistical knowledge. METHODS: A novel 3-D active contour method was employed to
      detect the left ventricular cavity in 33 subjects with heterogeneous heart
      diseases from the York University database. Papillary muscles were identified and
      added to the chamber using a convex hull of the left ventricle and interpolation.
      The myocardium was then segmented using a similar 3-D segmentation method
      according to anatomic information. A multistage approach was taken to determine
      the method's efficacy. RESULTS: Our method demonstrated a significant improvement
      in segmentation performance when compared to manual segmentation and other
      automated methods. CONCLUSION AND SIGNIFICANCE: A true 3-D reconstruction
      technique without the need for training datasets or any user-driven segmentation
      has been developed. In this method, a novel combination of internal and external
      energy terms for active contour was utilized that exploits histogram matching for
      improving the segmentation performance. This method takes advantage of full
      volumetric imaging, does not rely on prior statistical knowledge, and employs a
      convex-hull interpolation to include the papillary muscles.

PMID- 27046888
TI  - ConceFT for Time-Varying Heart Rate Variability Analysis as a Measure of Noxious
      Stimulation During General Anesthesia.
AB  - OBJECTIVE: Heart rate variability (HRV) offers a noninvasive way to peek into the
      physiological status of the human body. When this physiological status is
      dynamic, traditional HRV indices calculated from power spectrum do not resolve
      the dynamic situation due to the issue of nonstationarity. Clinical anesthesia is
      a typically dynamic situation that calls for time-varying HRV analysis.
      Concentration of frequency and time (ConceFT) is a nonlinear time-frequency (TF)
      analysis generalizing the multitaper technique and the synchrosqueezing
      transform. The result is a sharp TF representation capturing the dynamics inside
      HRV. Companion indices of the commonly applied HRV indices, including time
      varying low-frequency power (tvLF), time-varying high-frequency power, and time
      varying low-high ratio, are considered as measures of noxious stimulation.
      METHODS: To evaluate the feasibility of the proposed indices, we apply these
      indices to study two different types of noxious stimulation, the endotracheal
      intubation and surgical skin incision, under general anesthesia. The performance
      was compared with traditional HRV indices, the heart rate reading, and indices
      from electroencephalography. RESULTS: The results indicate that the tvLF index
      performs best and outperforms not only the traditional HRV index, but also the
      commonly used heart rate reading. CONCLUSION: With the help of ConceFT, the
      proposed HRV indices are potential to provide a better quantification of the
      dynamic change of the autonomic nerve system. SIGNIFICANCE: Our proposed scheme
      of time-varying HRV analysis could contribute to the clinical assessment of
      analgesia under general anesthesia.

PMID- 27046889
TI  - QRS Detection Algorithm for Telehealth Electrocardiogram Recordings.
AB  - OBJECTIVE: QRS detection algorithms are needed to analyze electrocardiogram (ECG)
      recordings generated in telehealth environments. However, the numerous published
      QRS detectors focus on clean clinical data. Here, a "UNSW" QRS detection
      algorithm is described that is suitable for clinical ECG and also poorer quality
      telehealth ECG. METHODS: The UNSW algorithm generates a feature signal containing
      information about ECG amplitude and derivative, which is filtered according to
      its frequency content and an adaptive threshold is applied. The algorithm was
      tested on clinical and telehealth ECG and the QRS detection performance is
      compared to the Pan-Tompkins (PT) and Gutierrez-Rivas (GR) algorithm. RESULTS:
      For the MIT-BIH Arrhythmia database (virtually artifact free, clinical ECG), the
      overall sensitivity (Se) and positive predictivity (+P) of the UNSW algorithm was
      >99%, which was comparable to PT and GR. When applied to the MIT-BIH noise stress
      test database (clinical ECG with added calibrated noise) after artifact masking,
      all three algorithms had overall Se >99%, and the UNSW algorithm had higher +P
      (98%, p < 0.05) than PT and GR. For 250 telehealth ECG records (unsupervised
      recordings; dry metal electrodes), the UNSW algorithm had 98% Se and 95% +P which
      was superior to PT (+P: p < 0.001) and GR (Se and +P: p < 0.001). CONCLUSION:
      This is the first study to describe a QRS detection algorithm for telehealth data
      and evaluate it on clinical and telehealth ECG with superior results to published
      algorithms. SIGNIFICANCE: The UNSW algorithm could be used to manage increasing
      telehealth ECG analysis workloads.

PMID- 27046890
TI  - Design and Validation of a Novel MR-Compatible Sensor for Respiratory Motion
      Modeling and Correction.
AB  - GOAL: A novel magnetic resonance (MR) compatible accelerometer for respiratory
      motion sensing (MARMOT) is developed as a surrogate of the vendors' pneumatic
      belts. We aim to model and correct respiratory motion for free-breathing thoracic
      abdominal MR imaging and to simplify patient installation. METHODS: MR
      compatibility of MARMOT sensors was assessed in phantoms and its motion
      modeling/correction efficacy was demonstrated on 21 subjects at 3 T. Respiration
      was modeled and predicted from MARMOT sensors and pneumatic belts, based on real
      time images and a regression method. The sensor accuracy was validated by
      comparing motion errors in the liver/kidney. Sensor data were also exploited as
      inputs for motion-compensated reconstruction of free-breathing cardiac cine MR
      images. Multiple and single sensor placement strategies were compared. RESULTS:
      The new sensor is compatible with the MR environment. The average motion modeling
      and prediction errors with MARMOT sensors and with pneumatic belts were
      comparable (liver and kidney) and were below 2 mm with all tested configurations
      (belts, multiple/single MARMOT sensor). Motion corrected cardiac cine images were
      of improved image quality, as assessed by an entropy metric (p  <  10-6), with
      all tested configurations. Expert readings revealed multiple MARMOT sensors were
      the best (p  <  0.03) and the single MARMOT sensor was similar to the belts
      (nonsignificant in two of the three readers). CONCLUSION: The proposed sensor can
      model and predict respiratory motion with sufficient accuracy to allow free
      breathing MR imaging strategy. SIGNIFICANCE: It provides an alternative sensor
      solution for the respiratory motion problem during MR imaging and may improve the
      convenience of patient setup.

PMID- 27046891
TI  - A Novel Grading Biomarker for the Prediction of Conversion From Mild Cognitive
      Impairment to Alzheimer's Disease.
AB  - OBJECTIVE: Identifying mild cognitive impairment (MCI) subjects who will progress
      to Alzheimer's disease (AD) is not only crucial in clinical practice, but also
      has a significant potential to enrich clinical trials. The purpose of this study
      is to develop an effective biomarker for an accurate prediction of MCI-to-AD
      conversion from magnetic resonance images. METHODS: We propose a novel grading
      biomarker for the prediction of MCI-to-AD conversion. First, we comprehensively
      study the effects of several important factors on the performance in the
      prediction task including registration accuracy, age correction, feature
      selection, and the selection of training data. Based on the studies of these
      factors, a grading biomarker is then calculated for each MCI subject using sparse
      representation techniques. Finally, the grading biomarker is combined with age
      and cognitive measures to provide a more accurate prediction of MCI-to-AD
      conversion. RESULTS: Using the Alzheimer's Disease Neuroimaging Initiative (ADNI)
      dataset, the proposed global grading biomarker achieved an area under the
      receiver operating characteristic curve (AUC) in the range of 79-81% for the
      prediction of MCI-to-AD conversion within three years in tenfold cross
      validations. The classification AUC further increases to 84-92% when age and
      cognitive measures are combined with the proposed grading biomarker. CONCLUSION:
      The obtained accuracy of the proposed biomarker benefits from the contributions
      of different factors: a tradeoff registration level to align images to the
      template space, the removal of the normal aging effect, selection of
      discriminative voxels, the calculation of the grading biomarker using AD and
      normal control groups, and the integration of sparse representation technique and
      the combination of cognitive measures. SIGNIFICANCE: The evaluation on the ADNI
      dataset shows the efficacy of the proposed biomarker and demonstrates a
      significant contribution in accurate prediction of MCI-to-AD conversion.

PMID- 27046892
TI  - A Hybrid Approach for Segmentation and Tracking of Myxococcus Xanthus Swarms.
AB  - Cell segmentation and motion tracking in time-lapse images are fundamental
      problems in computer vision, and are also crucial for various biomedical studies.
      Myxococcus xanthus is a type of rod-like cells with highly coordinated motion.
      The segmentation and tracking of M. xanthus are challenging, because cells may
      touch tightly and form dense swarms that are difficult to identify individually
      in an accurate manner. The known cell tracking approaches mainly fall into two
      frameworks, detection association and model evolution, each having its own
      advantages and disadvantages. In this paper, we propose a new hybrid framework
      combining these two frameworks into one and leveraging their complementary
      advantages. Also, we propose an active contour model based on the Ribbon Snake,
      which is seamlessly integrated with our hybrid framework. Evaluated by 10
      different datasets, our approach achieves considerable improvement over the state
      of-the-art cell tracking algorithms on identifying complete cell trajectories,
      and higher segmentation accuracy than performing segmentation in individual 2D
      images.

PMID- 27046893
TI  - Automatic Segmentation of MR Brain Images With a Convolutional Neural Network.
AB  - Automatic segmentation in MR brain images is important for quantitative analysis
      in large-scale studies with images acquired at all ages. This paper presents a
      method for the automatic segmentation of MR brain images into a number of tissue
      classes using a convolutional neural network. To ensure that the method obtains
      accurate segmentation details as well as spatial consistency, the network uses
      multiple patch sizes and multiple convolution kernel sizes to acquire multi-scale
      information about each voxel. The method is not dependent on explicit features,
      but learns to recognise the information that is important for the classification
      based on training data. The method requires a single anatomical MR image only.
      The segmentation method is applied to five different data sets: coronal T2
      weighted images of preterm infants acquired at 30 weeks postmenstrual age (PMA)
      and 40 weeks PMA, axial T2-weighted images of preterm infants acquired at 40
      weeks PMA, axial T1-weighted images of ageing adults acquired at an average age
      of 70 years, and T1-weighted images of young adults acquired at an average age of
      23 years. The method obtained the following average Dice coefficients over all
      segmented tissue classes for each data set, respectively: 0.87, 0.82, 0.84, 0.86,
      and 0.91. The results demonstrate that the method obtains accurate segmentations
      in all five sets, and hence demonstrates its robustness to differences in age and
      acquisition protocol.

PMID- 27046894
TI  - Reconstruction of 7T-Like Images From 3T MRI.
AB  - In the recent MRI scanning, ultra-high-field (7T) MR imaging provides higher
      resolution and better tissue contrast compared to routine 3T MRI, which may help
      in more accurate and early brain diseases diagnosis. However, currently, 7T MRI
      scanners are more expensive and less available at clinical and research centers.
      These motivate us to propose a method for the reconstruction of images close to
      the quality of 7T MRI, called 7T-like images, from 3T MRI, to improve the quality
      in terms of resolution and contrast. By doing so, the post-processing tasks, such
      as tissue segmentation, can be done more accurately and brain tissues details can
      be seen with higher resolution and contrast. To do this, we have acquired a
      unique dataset which includes paired 3T and 7T images scanned from same subjects,
      and then propose a hierarchical reconstruction based on group sparsity in a novel
      multi-level Canonical Correlation Analysis (CCA) space, to improve the quality of
      3T MR image to be 7T-like MRI. First, overlapping patches are extracted from the
      input 3T MR image. Then, by extracting the most similar patches from all the
      aligned 3T and 7T images in the training set, the paired 3T and 7T dictionaries
      are constructed for each patch. It is worth noting that, for the training, we use
      pairs of 3T and 7T MR images from each training subject. Then, we propose multi
      level CCA to map the paired 3T and 7T patch sets to a common space to increase
      their correlations. In such space, each input 3T MRI patch is sparsely
      represented by the 3T dictionary and then the obtained sparse coefficients are
      used together with the corresponding 7T dictionary to reconstruct the 7T-like
      patch. Also, to have the structural consistency between adjacent patches, the
      group sparsity is employed. This reconstruction is performed with changing patch
      sizes in a hierarchical framework. Experiments have been done using 13 subjects
      with both 3T and 7T MR images. The results show that our method outperforms
      previous methods and is able to recover better structural details. Also, to place
      our proposed method in a medical application context, we evaluated the influence
      of post-processing methods such as brain tissue segmentation on the reconstructed
      7T-like MR images. Results show that our 7T-like images lead to higher accuracy
      in segmentation of white matter (WM), gray matter (GM), cerebrospinal fluid
      (CSF), and skull, compared to segmentation of 3T MR images.

PMID- 27046895
TI  - High-Frequency Ultrasound Array Designed for Ultrasound-Guided Breast Biopsy.
AB  - This paper describes the development of a miniaturized high-frequency linear
      array that can be integrated within a core biopsy needle to improve tissue
      sampling accuracy during breast cancer biopsy procedures. The 64-element linear
      array has an element width of [Formula: see text], kerf width of [Formula: see
      text], element length of 1 mm, and element thickness of [Formula: see text]. The
      2-2 array composite was fabricated using deep reactive ion etching of lead
      magnesium niobate-lead titanate (PMN-PT) single crystal material. The array
      composite fabrication process as well as a novel high-density electrical
      interconnect solution are presented and discussed. Array performance measurements
      show that the array had a center frequency and fractional bandwidth ([Formula:
      see text]) of 59.1 MHz and 29.4%, respectively. Insertion loss and adjacent
      element crosstalk at the center frequency were -41.0 and [Formula: see text],
      respectively. A B-mode image of a tungsten wire target phantom was captured using
      a synthetic aperture imaging system and the imaging test results demonstrate
      axial and lateral resolutions of 33.2 and [Formula: see text], respectively.

PMID- 27046896
TI  - Quantitative Characterization of Tissue Microstructure in Concentrated Cell
      Pellet Biophantoms Based on the Structure Factor Model.
AB  - Quantitative ultrasound (QUS) methods based on the backscatter coefficient (BSC)
      are typically model-based. The BSC is estimated from experiments and is fit to a
      model. The fit parameters are often termed QUS estimates and are used to
      characterize the scattering properties of the tissue under investigation.
      Nevertheless, for physical interpretation of QUS estimates to be accurate, the
      scattering model chosen must also be accurate. The goal of this work was to
      investigate the use of the structure factor model (SFM) to take into account
      coherent scattering from high volume fractions of scatterers. The study focuses
      on comparing the performance of two sparse models (fluid-filled sphere and
      Gaussian) and one concentrated model (SFM) to estimate QUS parameters from
      simulations and cell pellet biophantoms with a range of scatterer volume
      fractions. Results demonstrated the superiority of the SFM for all investigated
      volume fractions (i.e., from 0.006 to 0.30). In particular, the sparse models
      underestimated scatterer size and overestimated acoustic concentration when the
      volume fraction was greater than 0.12. In addition, the SFM has the ability to
      provide the volume fraction and the relative impedance contrast (instead of only
      the acoustic concentration provided by the sparse models), which could have a
      great benefit for tissue characterization. This study demonstrates that the SFM
      could prove to be an invaluable tool for QUS and could help to more accurately
      characterize tissue from ultrasound measurements.

PMID- 27046897
TI  - Compact Representation of High-Dimensional Feature Vectors for Large-Scale Image
      Recognition and Retrieval.
AB  - In large-scale visual recognition and image retrieval tasks, feature vectors,
      such as Fisher vector (FV) or the vector of locally aggregated descriptors
      (VLAD), have achieved state-of-the-art results. However, the combination of the
      large numbers of examples and high-dimensional vectors necessitates
      dimensionality reduction, in order to reduce its storage and CPU costs to a
      reasonable range. In spite of the popularity of various feature compression
      methods, this paper shows that the feature (dimension) selection is a better
      choice for high-dimensional FV/VLAD than the feature (dimension) compression
      methods, e.g., product quantization. We show that strong correlation among the
      feature dimensions in the FV and the VLAD may not exist, which renders feature
      selection a natural choice. We also show that, many dimensions in FV/VLAD are
      noise. Throwing them away using feature selection is better than compressing them
      and useful dimensions altogether using feature compression methods. To choose
      features, we propose an efficient importance sorting algorithm considering both
      the supervised and unsupervised cases, for visual recognition and image
      retrieval, respectively. Combining with the 1-bit quantization, feature selection
      has achieved both higher accuracy and less computational cost than feature
      compression methods, such as product quantization, on the FV and the VLAD image
      representations.

PMID- 27046898
TI  - Antipodally Invariant Metrics for Fast Regression-Based Super-Resolution.
AB  - Dictionary-based super-resolution (SR) algorithms usually select dictionary atoms
      based on the distance or similarity metrics. Although the optimal selection of
      the nearest neighbors is of central importance for such methods, the impact of
      using proper metrics for SR has been overlooked in literature, mainly due to the
      vast usage of Euclidean distance. In this paper, we present a very fast
      regression-based algorithm, which builds on the densely populated anchored
      neighborhoods and sublinear search structures. We perform a study of the nature
      of the features commonly used for SR, observing that those features usually lie
      in the unitary hypersphere, where every point has a diametrically opposite one,
      i.e., its antipode, with same module and angle, but the opposite direction. Even
      though, we validate the benefits of using antipodally invariant metrics, most of
      the binary splits use Euclidean distance, which does not handle antipodes
      optimally. In order to benefit from both the worlds, we propose a simple yet
      effective antipodally invariant transform that can be easily included in the
      Euclidean distance calculation. We modify the original spherical hashing
      algorithm with this metric in our antipodally invariant spherical hashing scheme,
      obtaining the same performance as a pure antipodally invariant metric. We round
      up our contributions with a novel feature transform that obtains a better coarse
      approximation of the input image thanks to iterative backprojection. The
      performance of our method, which we named antipodally invariant SR, improves
      quality (Peak Signal to Noise Ratio) and it is faster than any other state-of-the
      art method.

PMID- 27046899
TI  - Adaptive Pairing Reversible Watermarking.
AB  - This letter revisits the pairwise reversible watermarking scheme of Ou et al.,
      2013. An adaptive pixel pairing that considers only pixels with similar
      prediction errors is introduced. This adaptive approach provides an increased
      number of pixel pairs where both pixels are embedded and decreases the number of
      shifted pixels. The adaptive pairwise reversible watermarking outperforms the
      state-of-the-art low embedding bit-rate schemes proposed so far.

PMID- 27046900
TI  - Multi-Label Dictionary Learning for Image Annotation.
AB  - Image annotation has attracted a lot of research interest, and multi-label
      learning is an effective technique for image annotation. How to effectively
      exploit the underlying correlation among labels is a crucial task for multi-label
      learning. Most existing multi-label learning methods exploit the label
      correlation only in the output label space, leaving the connection between the
      label and the features of images untouched. Although, recently some methods
      attempt toward exploiting the label correlation in the input feature space by
      using the label information, they cannot effectively conduct the learning process
      in both the spaces simultaneously, and there still exists much room for
      improvement. In this paper, we propose a novel multi-label learning approach,
      named multi-label dictionary learning (MLDL) with label consistency
      regularization and partial-identical label embedding MLDL, which conducts MLDL
      and partial-identical label embedding simultaneously. In the input feature space,
      we incorporate the dictionary learning technique into multi-label learning and
      design the label consistency regularization term to learn the better
      representation of features. In the output label space, we design the partial
      identical label embedding, in which the samples with exactly same label set can
      cluster together, and the samples with partial-identical label sets can
      collaboratively represent each other. Experimental results on the three widely
      used image datasets, including Corel 5K, IAPR TC12, and ESP Game, demonstrate the
      effectiveness of the proposed approach.

PMID- 27046901
TI  - Speeding Up the Bilateral Filter: A Joint Acceleration Way.
AB  - Computational complexity of the brute-force implementation of the bilateral
      filter (BF) depends on its filter kernel size. To achieve the constant-time BF
      whose complexity is irrelevant to the kernel size, many techniques have been
      proposed, such as 2D box filtering, dimension promotion, and shiftability
      property. Although each of the above techniques suffers from accuracy and
      efficiency problems, previous algorithm designers were used to take only one of
      them to assemble fast implementations due to the hardness of combining them
      together. Hence, no joint exploitation of these techniques has been proposed to
      construct a new cutting edge implementation that solves these problems. Jointly
      employing five techniques: kernel truncation, best N-term approximation as well
      as previous 2D box filtering, dimension promotion, and shiftability property, we
      propose a unified framework to transform BF with arbitrary spatial and range
      kernels into a set of 3D box filters that can be computed in linear time. To the
      best of our knowledge, our algorithm is the first method that can integrate all
      these acceleration techniques and, therefore, can draw upon one another's strong
      point to overcome deficiencies. The strength of our method has been corroborated
      by several carefully designed experiments. In particular, the filtering accuracy
      is significantly improved without sacrificing the efficiency at running time.

PMID- 27046902
TI  - A Systematic Review of Experimental Studies on Data Glyphs.
AB  - We systematically reviewed 64 user-study papers on data glyphs to help
      researchers and practitioners gain an informed understanding of tradeoffs in the
      glyph design space. The glyphs we consider are individual representations of
      multi-dimensional data points, often meant to be shown in small-multiple
      settings. Over the past 60 years many different glyph designs were proposed and
      many of these designs have been subjected to perceptual or comparative
      evaluations. Yet, a systematic overview of the types of glyphs and design
      variations tested, the tasks under which they were analyzed, or even the study
      goals and results does not yet exist. In this paper we provide such an overview
      by systematically sampling and tabulating the literature on data glyph studies,
      listing their designs, questions, data, and tasks. In addition we present a
      concise overview of the types of glyphs and their design characteristics analyzed
      by researchers in the past, and a synthesis of the study results. Based on our
      meta analysis of all results we further contribute a set of design implications
      and a discussion on open research directions.

PMID- 27046903
TI  - Wearable Barometric Pressure Sensor to Improve Postural Transition Recognition of
      Mobility-Impaired Stroke Patients.
AB  - Sit-to-stand and Stand-to-sit transfers (STS) provide relevant information
      regarding the functional limitation of mobility-impaired patients. The
      characterization of STS pattern using a single trunk fixed inertial sensor has
      been proposed as an objective tool to assess changes in functional ability and
      balance due to disease. Despite significant research efforts, STS quantification
      remains challenging due to the high inter- and between- subject variability of
      this motion pattern. The present study aims to improve the performance of STS
      detection and classification by fusing the information from barometric pressure
      (BP) and inertial sensors while keeping a single sensor located at the trunk. A
      total number of 345 STSs were recorded from 12 post-stroke patients monitored in
      a semi-structured conditioned protocol. Model-based features of BP signal were
      combined with kinematic parameters from accelerometer and/or gyroscope and used
      in a logistic regression-based classifier to detect STS and then identify their
      types. The correct classification rate was 90.6% with full sensor (BP and
      inertial) configuration and 75.4% with single inertial sensor. Receiver-Operating
      Characteristics analysis was carried out to characterize the robustness of the
      models. The results demonstrate the potential of BP sensor to improve the
      detection and classification of STSs when monitoring is performed unobtrusively
      in every-day life.

PMID- 27046904
TI  - Versatile Stimulation Back-End With Programmable Exponential Current Pulse Shapes
      for a Retinal Visual Prosthesis.
AB  - This paper reports on the design, implementation, and test of a stimulation back
      end, for an implantable retinal prosthesis. In addition to traditional
      rectangular pulse shapes, the circuit features biphasic stimulation pulses with
      both rising and falling exponential shapes, whose time constants are digitally
      programmable. A class-B second generation current conveyor is used as a wide
      swing, high-output-resistance stimulation current driver, delivering stimulation
      current pulses of up to +/-96 MUA to the target tissue. Duration of the generated
      current pulses is programmable within the range of 100 MUs to 3 ms. Current-mode
      digital-to-analog converters (DACs) are used to program the amplitudes of the
      stimulation pulses. Fabricated using the IBM 130 nm process, the circuit consumes
      1.5*1.5 mm2 of silicon area. According to the measurements, the DACs exhibit DNL
      and INL of 0.23 LSB and 0.364 LSB, respectively. Experimental results indicate
      that the stimuli generator meets expected requirements when connected to
      electrode-tissue impedance of as high as 25 k Omega. Maximum power consumption of
      the proposed design is 3.4 mW when delivering biphasic rectangular pulses to the
      target load. A charge pump block is in charge of the upconversion of the standard
      1.2-V supply voltage to +/-3.3V.

PMID- 27046905
TI  - Test and Validation of a Smart Exercise Bike for Motor Rehabilitation in
      Individuals With Parkinson's Disease.
AB  - To assess and validate the Smart Exercise Bike designed for Parkinson's Disease
      (PD) rehabilitation, 47 individuals with PD were randomly assigned to either the
      static or dynamic cycling group, and completed three sessions of exercise. Heart
      rate, cadence and power data were captured and recorded for each patient during
      exercise. Motor function for each subject was assessed with the UPDRS Motor III
      test before and after the three exercise sessions to evaluate the effect of
      exercise on functional abilities. Individuals who completed three sessions of
      dynamic cycling showed an average of 13.8% improvement in the UPDRS, while
      individuals in the static cycling group worsened by 1.6% in UPDRS. To distinguish
      the static and dynamic cycling groups by biomechanical and physiological
      features, the complexity of the recorded signals (cadence, power, and heart rate)
      was examined using approximate entropy (ApEn), sample entropy (SaEn) and spectral
      entropy (SpEn) as measures of variability. A multiple linear regression (MLR)
      model was used to relate these features to changes in motor function as measured
      by the UPDRS Motor III scale. Pattern variability in cadence was greater in the
      dynamic group when compared to the static group. In contrast, variability in
      power was greater for the static group. UPDRS Motor III scores predicted from the
      pattern variability data were correlated to measured scores in both groups. These
      results support our previous study which explained how variability analysis
      results for biomechanical and physiological parameters of exercise can be used to
      predict improvements in motor function.

PMID- 27046906
TI  - Signalign: An Ontology of DNA as Signal for Comparative Gene Structure Prediction
      Using Information-Coding-and-Processing Techniques.
AB  - Conventional character-analysis-based techniques in genome analysis manifest
      three main shortcomings-inefficiency, inflexibility, and incompatibility. In our
      previous research, a general framework, called DNA As X was proposed for
      character-analysis-free techniques to overcome these shortcomings, where X is the
      intermediates, such as digit, code, signal, vector, tree, graph network, and so
      on. In this paper, we further implement an ontology of DNA As Signal, by
      designing a tool named Signalign for comparative gene structure analysis, in
      which DNA sequences are converted into signal series, processed by modified
      method of dynamic time warping and measured by signal-to-noise ratio (SNR). The
      ontology of DNA As Signal integrates the principles and concepts of other
      disciplines including information coding theory and signal processing into
      sequence analysis and processing. Comparing with conventional character-analysis
      based methods, Signalign can not only have the equivalent or superior
      performance, but also enrich the tools and the knowledge library of computational
      biology by extending the domain from character/string to diverse areas. The
      evaluation results validate the success of the character-analysis-free technique
      for improved performances in comparative gene structure prediction.

PMID- 27046907
TI  - Comparison of Walking and Traveling-Wave Piezoelectric Motors as Actuators in
      Kinesthetic Haptic Devices.
AB  - Piezoelectric motors offer an attractive alternative to electromagnetic actuators
      in portable haptic interfaces: they are compact, have a high force-to-volume
      ratio, and can operate with limited or no gearing. However, the choice of a
      piezoelectric motor type is not obvious due to differences in performance
      characteristics. We present our evaluation of two commercial, operationally
      different, piezoelectric motors acting as actuators in two kinesthetic haptic
      grippers, a walking quasi-static motor and a traveling wave ultrasonic motor. We
      evaluate each gripper's ability to display common virtual objects including
      springs, dampers, and rigid walls, and conclude that the walking quasi-static
      motor is superior at low velocities. However, for applications where high
      velocity is required, traveling wave ultrasonic motors are a better option.

PMID- 27046909
TI  - A Collective Neurodynamic Approach to Constrained Global Optimization.
AB  - Global optimization is a long-lasting research topic in the field of
      optimization, posting many challenging theoretic and computational issues. This
      paper presents a novel collective neurodynamic method for solving constrained
      global optimization problems. At first, a one-layer recurrent neural network
      (RNN) is presented for searching the Karush-Kuhn-Tucker points of the
      optimization problem under study. Next, a collective neuroydnamic optimization
      approach is developed by emulating the paradigm of brainstorming. Multiple RNNs
      are exploited cooperatively to search for the global optimal solutions in a
      framework of particle swarm optimization. Each RNN carries out a precise local
      search and converges to a candidate solution according to its own neurodynamics.
      The neuronal state of each neural network is repetitively reset by exchanging
      historical information of each individual network and the entire group. Wavelet
      mutation is performed to avoid prematurity, add diversity, and promote global
      convergence. It is proved in the framework of stochastic optimization that the
      proposed collective neurodynamic approach is capable of computing the global
      optimal solutions with probability one provided that a sufficiently large number
      of neural networks are utilized. The essence of the collective neurodynamic
      optimization approach lies in its potential to solve constrained global
      optimization problems in real time. The effectiveness and characteristics of the
      proposed approach are illustrated by using benchmark optimization problems.

PMID- 27046912
TI  - Sparseness Analysis in the Pretraining of Deep Neural Networks.
AB  - A major progress in deep multilayer neural networks (DNNs) is the invention of
      various unsupervised pretraining methods to initialize network parameters which
      lead to good prediction accuracy. This paper presents the sparseness analysis on
      the hidden unit in the pretraining process. In particular, we use the L1 -norm to
      measure sparseness and provide some sufficient conditions for that pretraining
      leads to sparseness with respect to the popular pretraining models-such as
      denoising autoencoders (DAEs) and restricted Boltzmann machines (RBMs). Our
      experimental results demonstrate that when the sufficient conditions are
      satisfied, the pretraining models lead to sparseness. Our experiments also reveal
      that when using the sigmoid activation functions, pretraining plays an important
      sparseness role in DNNs with sigmoid (Dsigm), and when using the rectifier linear
      unit (ReLU) activation functions, pretraining becomes less effective for DNNs
      with ReLU (Drelu). Luckily, Drelu can reach a higher recognition accuracy than
      DNNs with pretraining (DAEs and RBMs), as it can capture the main benefit (such
      as sparseness-encouraging) of pretraining in Dsigm. However, ReLU is not adapted
      to the different firing rates in biological neurons, because the firing rate
      actually changes along with the varying membrane resistances. To address this
      problem, we further propose a family of rectifier piecewise linear units (RePLUs)
      to fit the different firing rates. The experimental results show that the
      performance of RePLU is better than ReLU, and is comparable with those with some
      pretraining techniques, such as RBMs and DAEs.

PMID- 27046916
TI  - Finite-Time Control for Robust Tracking Consensus in MASs With an Uncertain
      Leader.
AB  - This paper investigates the finite-time control for robust tracking consensus
      problems of multiagent systems with an uncertain leader for situations where the
      state of the considered active leader may not be measured and the directed
      network topology is time-varying. Based on the neighbor-based state-estimation
      rule and a new Lyapunov stability analysis method, a continuous and nonlinear
      distributed tracking protocol using only relative position information is
      designed, under which each agent can follow the leader in finite time if the
      input (acceleration) of the leader is known, and the tracking errors can converge
      to a bounded region in finite time if the input of the leader is unknown. In
      particular, a special continuous distributed tracking protocol with bounded
      control inputs is introduced to track the active leader in finite time. Numerical
      simulations are also given to illustrate the effectiveness of the theoretic
      results.

PMID- 27046917
TI  - Multiagent Reinforcement Learning With Sparse Interactions by Negotiation and
      Knowledge Transfer.
AB  - Reinforcement learning has significant applications for multiagent systems,
      especially in unknown dynamic environments. However, most multiagent
      reinforcement learning (MARL) algorithms suffer from such problems as exponential
      computation complexity in the joint state-action space, which makes it difficult
      to scale up to realistic multiagent problems. In this paper, a novel algorithm
      named negotiation-based MARL with sparse interactions (NegoSIs) is presented. In
      contrast to traditional sparse-interaction-based MARL algorithms, NegoSI adopts
      the equilibrium concept and makes it possible for agents to select the nonstrict
      equilibrium-dominating strategy profile (nonstrict EDSP) or meta equilibrium for
      their joint actions. The presented NegoSI algorithm consists of four parts: 1)
      the equilibrium-based framework for sparse interactions; 2) the negotiation for
      the equilibrium set; 3) the minimum variance method for selecting one joint
      action; and 4) the knowledge transfer of local Q -values. In this integrated
      algorithm, three techniques, i.e., unshared value functions, equilibrium
      solutions, and sparse interactions are adopted to achieve privacy protection,
      better coordination and lower computational complexity, respectively. To evaluate
      the performance of the presented NegoSI algorithm, two groups of experiments are
      carried out regarding three criteria: 1) steps of each episode; 2) rewards of
      each episode; and 3) average runtime. The first group of experiments is conducted
      using six grid world games and shows fast convergence and high scalability of the
      presented algorithm. Then in the second group of experiments NegoSI is applied to
      an intelligent warehouse problem and simulated results demonstrate the
      effectiveness of the presented NegoSI algorithm compared with other state-of-the
      art MARL algorithms.

PMID- 27046918
TI  - Steering of Magnetic Devices With a Magnetic Particle Imaging System.
AB  - Small magnetic devices have been steered in arbitrary direction and with variable
      force using a preclinical demonstrator system for magnetic particle imaging
      (MPI). Fast localization due to the high imaging rate of over 40 volumes/s and
      strong forces due to the high field gradient of more than 1 T/m render an MPI
      system, a good platform for image-guided steering of magnetic devices. In this
      paper, these capabilities are demonstrated in phantom experiments, where a closed
      feedback loop has been realized to exert translational forces in horizontal and
      vertical direction on a magnetic device moving in a viscous medium. The MPI
      system allows for the controlled application of those forces by combining
      variable homogeneous fields with strong field gradients.

PMID- 27046919
TI  - Latent Max-Margin Multitask Learning With Skelets for 3-D Action Recognition.
AB  - Recent emergence of low-cost and easy-operating depth cameras has reinvigorated
      the research in skeleton-based human action recognition. However, most existing
      approaches overlook the intrinsic interdependencies between skeleton joints and
      action classes, thus suffering from unsatisfactory recognition performance. In
      this paper, a novel latent max-margin multitask learning model is proposed for 3
      D action recognition. Specifically, we exploit skelets as the mid-level
      granularity of joints to describe actions. We then apply the learning model to
      capture the correlations between the latent skelets and action classes each of
      which accounts for a task. By leveraging structured sparsity inducing
      regularization, the common information belonging to the same class can be
      discovered from the latent skelets, while the private information across
      different classes can also be preserved. The proposed model is evaluated on three
      challenging action data sets captured by depth cameras. Experimental results show
      that our model consistently achieves superior performance over recent state-of
      the-art approaches.

PMID- 27046920
TI  - Temporal Restricted Visual Tracking Via Reverse-Low-Rank Sparse Learning.
AB  - An effective representation model, which aims to mine the most meaningful
      information in the data, plays an important role in visual tracking. Some recent
      particle-filter-based trackers achieve promising results by introducing the low
      rank assumption into the representation model. However, their assumed low-rank
      structure of candidates limits the robustness when facing severe challenges such
      as abrupt motion. To avoid the above limitation, we propose a temporal restricted
      reverse-low-rank learning algorithm for visual tracking with the following
      advantages: 1) the reverse-low-rank model jointly represents target and
      background templates via candidates, which exploits the low-rank structure among
      consecutive target observations and enforces the temporal consistency of target
      in a global level; 2) the appearance consistency may be broken when target
      suffers from sudden changes. To overcome this issue, we propose a local
      constraint via l1,2 mixed-norm, which can not only ensures the local consistency
      of target appearance, but also tolerates the sudden changes between two adjacent
      frames; and 3) to alleviate the inference of unreasonable representation values
      due to outlier candidates, an adaptive weighted scheme is designed to improve the
      robustness of the tracker. By evaluating on 26 challenge video sequences, the
      experiments show the effectiveness and favorable performance of the proposed
      algorithm against 12 state-of-the-art visual trackers.

PMID- 27046921
TI  - An Approximate Approach to Automatic Kernel Selection.
AB  - Kernel selection is a fundamental problem of kernel-based learning algorithms. In
      this paper, we propose an approximate approach to automatic kernel selection for
      regression from the perspective of kernel matrix approximation. We first
      introduce multilevel circulant matrices into automatic kernel selection, and
      develop two approximate kernel selection algorithms by exploiting the
      computational virtues of multilevel circulant matrices. The complexity of the
      proposed algorithms is quasi-linear in the number of data points. Then, we prove
      an approximation error bound to measure the effect of the approximation in kernel
      matrices by multilevel circulant matrices on the hypothesis and further show that
      the approximate hypothesis produced with multilevel circulant matrices converges
      to the accurate hypothesis produced with kernel matrices. Experimental
      evaluations on benchmark datasets demonstrate the effectiveness of approximate
      kernel selection.

PMID- 27046922
TI  - Squamous cell carcinoma on the lip arising from discoid lupus erythematosus: a
      case report and review of Japanese patients.

PMID- 27046923
TI  - Purpura fulminans related to paroxysmal nocturnal haemoglobinuria.

PMID- 27046924
TI  - [Medecine et Sante Tropicales: Four years now].

PMID- 27046925
TI  - [The double standard: Zika].

PMID- 27046926
TI  - [Leon Lapeyssonnie On the trail to its end].
AB  - He would have celebrated his 100th birthday in 2015, but finally, it doesn't
      matter, since by leaving his name to African meningitis belt, that isohyetal band
      in sub-Saharan Africa where epidemics of cerebrospinal meningitis are rife,
      Lapeyssonnie, the trailblazer at the end of his trail, has gone straight into the
      textbooks of tropical medicine. There was probably nothing he enjoyed more than
      wandering the lateritic paths and Sudano-Sahelian bush in that zone. His first
      job, in the Mossi country in Upper Volta that had not yet become Burkina Faso,
      was of course an initiation. At the age of 27, applying the Jamot doctrine and
      tracking the vectors of sleeping sickness down into the most remote villages,
      like his illustrious predecessor, the young physician who became a Physician
      General never stopped defending these precepts of tropical public health and
      promoting the "eccentric battalions" (as the English physicians, Dr Waddy,
      described them) of bush doctors from the School of Pharo (Army Institute of
      Tropical Medicine in Marseille). Foreshadowing the French doctors and "without
      borders" movement, Lapeyssonnie was able to implement the results of research in
      vaccinology. Thus, in 1974, during a meningitis epidemic in Brazil, he convinced
      Charles Merieux to manufacture the lifesaving vaccine on a large scale. Merieux
      then mobilized all the resources of his company to produce and deliver millions
      of doses of the only vaccine then available. Ten million inhabitants of Sao Paulo
      were vaccinated in five days, 90 million Brazilians in 6 months. Another victory
      at the end of the trail. But Lapeyssonnie was more than a man dealing with great
      endemics, more than a researcher and a teacher. "Those who liked to be taught
      like to teach in their turn," he liked to repeat, talking about his time at
      Pharo. Writer and novelist, he could sometimes write poetry, recount the bygone
      epoque when he went out hunting in the African bush and shared with nurses there
      unique moments of great humanity. It is probably because of this humanity that
      from his retirement in Brittany, in 2000, a year from the end of his trail, he
      could still inveigh in the Parisian newspaper, Le Monde, against the bureaucrats
      at the World Health Organization, who were asleep in the battle against sleeping
      sickness; his task then was to awaken consciences and Africa so that the
      populations at the end of the trail would not be forgotten. 

PMID- 27046927
TI  - [Clubfoot treatment: Implementation of the Ponseti method in emerging countries].
AB  - Idiopathic clubfoot is one of the most frequent congenital deformities throughout
      the world. The Ponseti method is the gold standard for its treatment. This
      simple, low-cost method is very effective and very appropriate for countries with
      resource-limited or otherwise precarious health services. It is based on
      correction of the deformity by successive castings associated with a percutaneous
      Achilles tenotomy and then foot abduction bracing to maintain the correction. The
      Ponseti method is now well implemented in most emerging countries, largely due to
      internet development, but some barriers still limit its diffusion. This study
      aims to determine the principal barriers, to suggest some improvements, and to
      stress the essential points of its effective utilization by non-physicians. 

PMID- 27046928
TI  - [Septic shock with multiple organ failure after returning from Southeast Asia].
AB  - For a patient recently returned from a tropical country in intensive care, the
      leading hypothesis for a fever leading to multiple organ failure is evidently
      malaria. Nonetheless, many other causes are possible and should be considered:
      parasites, viruses, and bacteria. A multidisciplinary discussion between
      specialists in emergency medicine, radiology, pathology, and infectious diseases
      is essential to start appropriate treatment as quickly as possible without
      impairing the patient's prognosis. 

PMID- 27046929
TI  - [Contextual factors regarding the effectiveness of tuberculosis control in
      Madagascar: a nationwide validity study].
AB  - INTRODUCTION: This study assesses the nationwide applicability of results from a
      study in the tuberculosis (TB) diagnostic and treatment centers (DTCs) in a
      sample of six districts in Madagascar, which identified adaptations of national
      guidelines and local initiatives that might explain the effectiveness of
      individual DTCs in improving adherence to TB treatment and thus reducing
      treatment default. OBJECTIVE: To assess, at a national level, the importance of
      these adaptations/initiatives for TB treatment adherence. METHODS: This
      analytical cross-sectional study assessed the responses to a questionnaire based
      on the previously identified adaptations/initiatives, which was sent to the heads
      of all 205 DTCs in Madagascar. RESULTS: Decentralization of TB care decreased the
      rate of patient default. The private DTCs report better results than public DTCs.
      Adaptations/initiatives in relation to local contexts often lead to good results.
      The relation between some adaptations/initiatives and continued adherence
      sometimes varies with the local context of the DTC; the same initiatives can
      result in better adherence or in higher of treatment default rates, depending on
      the setting. CONCLUSION: These initiatives should be applied after adaptation to
      the context.

PMID- 27046930
TI  - [Simple technique for autologous transfusion in ruptured ectopic pregnancy:
      Report of six cases managed at the Yaounde University Hospital in Cameroon].
AB  - Ruptured ectopic pregnancies are life-threatening emergencies, especially in
      developing countries, where many patients do not consult until rupture, sometimes
      with the patient already in hemorrhagic shock. In this situation, immediate blood
      transfusion is essential. Homologous blood products are not always available.
      Furthermore, homologous transfusion carries the risk of transmitting viruses such
      as HIV and hepatitis B and C. Autologous transfusion (intraoperative blood
      salvage) may thus be helpful. The authors present 6 cases of autologous
      transfusion performed at the Yaounde University Hospital (Cameroon) and recommend
      this method in developing countries where good quality blood cannot always be
      obtained rapidly. 

PMID- 27046931
TI  - [Prompt control of an imported carbapenem-resistant Acinetobacter baumanii
      outbreak in a French intensive care unit].
AB  - OBJECTIVE: to describe the management and control of a limited outbreak of
      carbapenem-resistant Acinetobacter baumanii (CRAB) outbreak in a French intensive
      care unit. METHODS: Careful review of the contact's and carrier's files and
      outbreak management procedures. RESULTS: An undiagnosed CRAB carrier was admitted
      to our intensive care unit after medical evacuation from Turkey. Despite
      preventive isolation and contact precautions, a secondary case was diagnosed 5
      days after admission of the index case and resulted in the creation of a crisis
      unit. Prompt management included an epidemiologic investigation with contact
      screening and follow-up, environmental screening, and additional restrictive
      measures: isolation room, closure of adjacent rooms, patient cohorting with
      designated nurses, and reinforcement of contact precautions. CONCLUSIONS:
      restrictive management of CRAB outbreaks may allow prompt outbreak control and
      avoid prolonged room closures.

PMID- 27046932
TI  - Asymmetry in Determinants of Running Speed During Curved Sprinting.
AB  - This study investigates the potential asymmetries between inside and outside legs
      in determinants of curved running speed. To test these asymmetries, a
      deterministic model of curved running speed was constructed based on components
      of step length and frequency, including the distances and times of different step
      phases, takeoff speed and angle, velocities in different directions, and relative
      height of the runner's center of gravity. Eighteen athletes sprinted 60 m on the
      curved path of a 400-m track; trials were recorded using a motion-capture system.
      The variables were calculated following the deterministic model. The average
      speeds were identical between the 2 sides; however, the step length and frequency
      were asymmetric. In straight sprinting, there is a trade-off relationship between
      the step length and frequency; however, such a trade-off relationship was not
      observed in each step of curved sprinting in this study. Asymmetric vertical
      velocity at takeoff resulted in an asymmetric flight distance and time. The
      runners changed the running direction significantly during the outside foot
      stance because of the asymmetric centripetal force. Moreover, the outside leg had
      a larger tangential force and shorter stance time. These asymmetries between legs
      indicated the outside leg plays an important role in curved sprinting. 

PMID- 27046933
TI  - The Effect of Stimulus Timing on Unplanned Gait Termination.
AB  - Gait termination can be challenging for balance-impaired populations, including
      lower limb amputees. As powered prosthetic ankle devices come to market, it is
      important to better understand gait termination timing in an unplanned situation.
      Timing patterns were examined in unplanned gait termination to determine a
      threshold for being able to terminate gait in 1 step. Time to terminate gait
      (TTG) was also examined, using both final heel strike and center of mass (COM)
      acceleration metrics. Fourteen able-bodied subjects walked over ground and
      terminated gait in response to a randomly-timed auditory stimulus. A lumbar
      mounted accelerometer and footswitches were used to assess timing of gait
      termination. Subjects were able to terminate gait in 1 step if the stimulus
      occurred at or before 19.8% of gait cycle. Later stimulus resulted in a 2-step
      stop pattern. The TTG using COM acceleration was greater than when using heel
      strike data. Motion of the COM was not fully arrested until 162 +/- 38% of gait
      cycle. The stabilization phase between heel strike and COM motion arrest was
      greater for 1-step stops (1.41 +/- 0.42 s) than 2-step stops (0.96 +/- 0.33 s).
      These findings indicate gait termination timing should be calculated using COM
      motion, including the stabilization phase post heel strike. 

PMID- 27046934
TI  - Modification of Impulse Generation During Pirouette Turns With Increased
      Rotational Demands.
AB  - This study determined how dancers regulated angular and linear impulse during the
      initiation of pirouettes of increased rotation. Skilled dancers (n = 11)
      performed single and double pirouette turns with each foot supported by a force
      plate. Linear and angular impulses generated by each leg were quantified and
      compared between turn types using probability-based statistical methods. As
      rotational demands increased, dancers increased the net angular impulse
      generated. The contribution of each leg to net angular impulse in both single and
      double pirouettes was influenced by stance configuration strategies. Dancers who
      generated more angular impulse with the push leg than with the turn leg initiated
      the turn with the center of mass positioned closer to the turn leg than did other
      dancers. As rotational demands increased, dancers tended to increase the
      horizontal reaction force magnitude at one or both feet; however, they used
      subject-specific mechanisms. By coordinating the generation of reaction forces
      between legs, changes in net horizontal impulse remained minimal, despite impulse
      regulation at each leg used to achieve more rotations. Knowledge gained regarding
      how an individual coordinates the generation of linear and angular impulse
      between both legs as rotational demand increased can help design tools to improve
      that individual's performance. 

PMID- 27046935
TI  - Adaptation of the Resistance Training Skills Battery for Use in Children Across
      the Motor Proficiency Spectrum.
AB  - PURPOSE: The study aim was to adapt the Resistance Training Skills Battery for
      use in children and assess its interrater and intrarater reliability. The RTSBc
      provides an assessment of resistance training (RT) skill competency and an
      indication of readiness to perform RT. The RTSBc includes 6 basic RT skills.
      Scoring for individual RT skills is based on the number of performance criteria
      correctly demonstrated and a gross resistance training skills quotient for
      children (RTSQc) is calculated by summing the individual skill scores. METHODS:
      Twenty participants (mean age = 8.2 +/- 1.8 years) were assessed while performing
      the RTSBc on 2 occasions. The 3 raters completing the assessments had varying
      levels of movement analysis and RT experience and received training in how to
      appraise RT skill competency using the RTSBc. RESULTS: Interrater reliability for
      the 3 raters was very good for the RTSQc (ICC = 0.92) and individual RT skills
      (ICC range = 0.82-0.94). Intrarater reliability of the live rater was also very
      good for the RTSQc (ICC = 0.97) and individual RT skills (ICC range = 0.87-0.95).
      CONCLUSION: This study has demonstrated the interrater and intrarater reliability
      of the RTSBc for children with varying levels of motor proficiency. The RTSBc can
      be used reliably within and between-raters to assess the RT skill competency of
      children.

PMID- 27046936
TI  - Maturity, Physical Ability, Technical Skill and Coaches' Perception of Semi-Elite
      Adolescent Australian Footballers.
AB  - PURPOSE: To confirm the effect of maturational differences on anthropometric and
      physical testing and explore the effect of maturation on technical skill and
      coaches' perceptions of skill in adolescent Australian footballers. METHODS:
      Athletes were recruited from a semielite under 16 competition (n = 94, age 15.7
      +/- 0.3 years) and completed anthropometric, physical, and technical skill tests.
      Coaches from each team provided subjective ratings of athletes' technical skills.
      Maturation groups were derived from years from peak height velocity estimates,
      with classifications either later, average or earlier maturing. RESULTS: Effect
      size comparisons revealed very large to moderate effects between groups for
      anthropometric measures and performance in sprint and jump tasks. Small to
      moderate effects were reported between groups for coaches' perceptions of skill,
      with the earlier maturing group perceived to have better overall technical
      skills, marking and ball winning abilities. Small to trivial effects were
      reported for performance in the technical skill tests. CONCLUSION: Despite no
      differences in skill tests, earlier maturing athletes may be afforded significant
      selection and competition advantages due to advanced physical capacities and
      coaches' perceptions of skill.

PMID- 27046937
TI  - Associations Between Balance and Muscle Strength, Power Performance in Male Youth
      Athletes of Different Maturity Status.
AB  - : Balance, strength and power relationships may contain important information at
      various maturational stages to determine training priorities. PURPOSE: The
      objective was to examine maturity-specific relationships of static/dynamic
      balance with strength and power measures in young male athletes. METHODS: Soccer
      players (N = 130) aged 10-16 were assessed with the Stork and Y balance (YBT)
      tests. Strength/power measures included back extensor muscle strength, standing
      long jump (SLJ), countermovement jump (CMJ), and 3-hop jump tests. Associations
      between balance with strength/power variables were calculated according to peak
      height-velocity (PHV). RESULTS: There were significant medium-large sized
      correlations between all balance measures with back extensor strength (r = .486
      .791) and large associations with power (r = .511-.827). These correlation
      coefficients were significantly different between pre-PHV and circa PHV as well
      as pre-PHV and post-PHV with larger associations in the more mature groups.
      Irrespective of maturity-status, SLJ was the best strength/power predictor with
      the highest proportion of variance (12-47%) for balance (i.e., Stork eyes opened)
      and the YBT was the best balance predictor with the highest proportion of
      variance (43-78%) for all strength/power variables. CONCLUSION: The associations
      between balance and muscle strength/power measures in youth athletes that
      increase with maturity may imply transfer effects from balance to strength/power
      training and vice versa in youth athletes.

PMID- 27046938
TI  - Optimal multiple testing under a Gaussian prior on the effect sizes.
AB  - We develop a new method for large-scale frequentist multiple testing with
      Bayesian prior information. We find optimal [Formula: see text]-value weights
      that maximize the average power of the weighted Bonferroni method. Due to the
      nonconvexity of the optimization problem, previous methods that account for
      uncertain prior information are suitable for only a small number of tests. For a
      Gaussian prior on the effect sizes, we give an efficient algorithm that is
      guaranteed to find the optimal weights nearly exactly. Our method can discover
      new loci in genome-wide association studies and compares favourably to
      competitors. An open-source implementation is available.

PMID- 27046939
TI  - Shared kernel Bayesian screening.
AB  - This article concerns testing for equality of distribution between groups. We
      focus on screening variables with shared distributional features such as common
      support, modes and patterns of skewness. We propose a Bayesian testing method
      using kernel mixtures, which improves performance by borrowing information across
      the different variables and groups through shared kernels and a common
      probability of group differences. The inclusion of shared kernels in a finite
      mixture, with Dirichlet priors on the weights, leads to a simple framework for
      testing that scales well for high-dimensional data. We provide closed asymptotic
      forms for the posterior probability of equivalence in two groups and prove
      consistency under model misspecification. The method is applied to DNA
      methylation array data from a breast cancer study, and compares favourably to
      competitors when Type I error is estimated via permutation.

PMID- 27046940
TI  - Optofluidic devices with integrated solid-state nanopores.
AB  - This review (with 90 refs.) covers the state of the art in optofluidic devices
      with integrated solid-state nanopores for use in detection and sensing. Following
      an introduction into principles of optofluidics and solid-state nanopore
      technology, we discuss features of solid-state nanopore based assays using
      optofluidics. This includes the incorporation of solid-state nanopores into
      optofluidic platforms based on liquid-core anti-resonant reflecting optical
      waveguides (ARROWs), methods for their fabrication, aspects of single particle
      detection and particle manipulation. We then describe the new functionalities
      provided by solid-state nanopores integrated into optofluidic chips, in
      particular acting as smart gates for correlated electro-optical detection and
      discrimination of nanoparticles. This enables the identification of viruses and
      lambda-DNA, particle trajectory simulations, enhancing sensitivity by tuning the
      shape of nanopores. The review concludes with a summary and an outlook.

PMID- 27046941
TI  - Hepato - Cephalic Index as a Predictor of Intrauterine Growth Restriction.
AB  - AIM: The aims of this study were to compare ultrasound fetoplacental parameters
      and to calculate Hepato-Cephalic Index (HCI) as a new predictor of IUGR. METHODS
      AND MATERIAL: A clinical prospective study was conducted and included 120
      pregnant women divided in two groups: non IUGR group included healthy pregnant
      women (n=60) and IUGR group included pregnant women with preeclampsia and IUGR
      (n=60). Outcome measures were following ultrasound fetoplacental parameters in
      fetuses with IUGR and non IUGR: Fetal Liver Length (FLL), Femur Length (FL),
      Biparietal Diameter (BPD), Placental Maturation by Grannum, Amniotic Fluid Index
      (AFI) and Hepato-Cephalic Index (HCI). Sonography was carried out by probe 3.5
      Mhz type MINDRAY DC 7. RESULTS: The mean of maternal age was 30.0+/-6.1 years in
      women with preeclampsia and IUGR and 28.1+/-5.1 years in healthy pregnant women,
      p > 0.05. There was a statistically significant difference in values of: FLL (p <
      0.001), FL (p = 0.004), BPD (p < 0.001), AFI (p < 0.001), HCI (p < 0.001) between
      IUGR and non IUGR groups. The most of women with preeclampsia and IUGR had grade
      III of placental maturation (48.3%). There is a significant association between
      the placental maturation and the diagnosis, p < 0.001. There was a statistically
      significant difference in body mass of newborns between IUGR and non IUGR groups,
      p < 0.001. CONCLUSION: In a fetus with IUGR in preeclampsia there is a reduction
      in FLL, FL, BPD, AFI and HCI and there is a early maturation of the placenta. By
      measurement of fetoplacental ultrasonic parameters of liver, pregnant women will
      experience prediction of risk pregnancy (preeclampsia with IUGR) due to hypoxia.

PMID- 27046942
TI  - Maximum Time of the Effect of Antileukotriene - Zileuton in Treatment of Patients
      with Bronchial Asthma.
AB  - OBJECTIVE: Maximum time of the effect of antileukotriene substances - Zileuton in
      the treatment of patients with bronchial asthma and increased bronchial
      reactivity and of the salbutamol as agonist of the beta2 adrenergic receptor
      studied in this work. METHODS: Parameters of the lung function are determined
      with Body plethysmography. Raw and ITGV were registered and specific resistance
      (SRaw) was calculated. Zileuton (Zyflo, tbl. 600 mg), producer Cornerstone
      Therapeutics, USA was used in the research. RESULTS: Results of this research, in
      patients with bronchial asthma, indicate that antileukotriene substances-Zileuton
      administered in a dose of 600 mg first day (oral route of administration 4 * 1
      tbl.) has not caused significant decrease of the specific resistance of the
      airways (SRaw) (p value 0.1 > Alpha 0.05), whereas Zileuton administered two days
      in a row, in a dose of 600 mg (4 * 1 tbl. a day), has caused significant decrease
      of the specific resistance of the airways (SRaw) (P value 0.03 < Alpha 0.05).
      Effect of the control with salbutamol (beta2-adrenergic receptor agonist) is
      efficient in the removal of the increased bronchomotor tone, causing significant
      decrease of the resistance (Raw), respectively of the specific resistance (SRaw),
      (p value 0.05 = Alpha 0.05). CONCLUSION: Formation of leukotrienes depends on the
      lypoxygenation of the arachidonic acid by 5-lypoxygenase. Zileuton is an active
      and powerful inhibitor of the activity of 5- lypoxygenase and as such inhibits
      generation of its products. Consequently, besides inhibition of cys-LTs',
      zileuton also inhibits the formation of leukotriene B4 (LTB4), which is a
      powerful chemotactic of other eicosanoids too, which depend on the synthesis of
      lekotriene A4 (LTA4). This suggests that the effect of antileukotrienes
      (Zileuton) is not immediate after oral administration, but the powerful effect of
      the Zileuton seen only after two days of inhibition of cys-LTs', and inhibition
      of leukotriene B4 (LTB4) and A4 (LTA4).

PMID- 27046943
TI  - The Diagnostic Value of Skin Disease Diagnosis Expert System.
AB  - BACKGROUND: Evaluation is a necessary measure to ensure the effectiveness and
      efficiency of all systems, including expert systems. The aim of this study was to
      determine the diagnostic value of expert system for diagnosis of complex skin
      diseases. METHODS: A case-control study was conducted in 2015 to determine the
      diagnostic value of an expert system. The study population included patients who
      were referred to Razi Specialized Hospital, affiliated to Tehran University of
      Medical Sciences. The control group was selected from patients without the
      selected skin diseases. Data collection tool was a checklist of clinical signs of
      diseases including pemphigus vulgaris, lichen planus, basal cell carcinoma,
      melanoma, and scabies. The sample size formula estimated 400 patients with skin
      diseases selected by experts and 200 patients without the selected skin diseases.
      Patient selection was undertaken with randomized stratified sampling and their
      sign and symptoms were logged into the system. Physician's diagnosis was
      determined as the gold standard and was compared with the diagnosis of expert
      system by SPSS software version 16 and STATA. Kappa statistics, indicators of
      sensitivity, specificity, accuracy and confidence intervals were calculated for
      each disease. An accuracy of 90% was considered appropriate. RESULTS: Comparing
      the results of expert system and physician's diagnosis at the evaluation stage
      showed an accuracy of 97.1%, sensitivity of 97.5% and specificity of 96.5% The
      Kappa test indicated a high agreement of 93.6%. CONCLUSION: The expert system can
      diagnose complex skin diseases. Development of such systems is recommended to
      identify all skin diseases.

PMID- 27046944
TI  - Health Information Security in Hospitals: the Application of Security Safeguards.
AB  - INTRODUCTION: A hospital information system has potentials to improve the
      accessibility of clinical information and the quality of health care. However,
      the use of this system has resulted in new challenges, such as concerns over
      health information security. This paper aims to assess the status of information
      security in terms of administrative, technical and physical safeguards in the
      university hospitals. METHODS: This was a survey study in which the participants
      were information technology (IT) managers (n=36) who worked in the hospitals
      affiliated to the top ranked medical universities (university A and university
      B). Data were collected using a questionnaire. The content validity of the
      questionnaire was examined by the experts and the reliability of the
      questionnaire was determined using Cronbach's coefficient alpha (alpha=0.75).
      RESULTS: The results showed that the administrative safeguards were arranged at a
      medium level. In terms of the technical safeguards and the physical safeguards,
      the IT managers rated them at a strong level. CONCLUSION: According to the
      results, among three types of security safeguards, the administrative safeguards
      were assessed at the medium level. To improve it, developing security policies,
      implementing access control models and training users are recommended.

PMID- 27046945
TI  - The Most Influential Scientist in the Development of Medical informatics (10):
      Marsden S. Blois.

PMID- 27046946
TI  - Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced
      Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis.
AB  - BACKGROUND: To differentiate the features of electroencephalography (EEG) after
      status epileptics in febrile children with final diagnosis of either febrile
      seizure (FS) or acute encephalopathy for an early diagnosis. METHODS: We
      retrospectively collected data from 68 children who had status epilepticus and
      for whom EEGs were recorded within 120 h. These included subjects with a final
      diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy
      with biphasic seizures and late reduced diffusion (AESD; n = 18), mild
      encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile
      encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and
      intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and
      graded, and correlation with outcome was explored. Representative EEG epochs were
      then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and
      FS (n = 16) patients for whom EEG was recorded within 24 h were also compared.
      RESULTS: Although milder and most severe grades of EEG correlated with
      neurological outcome, the outcome of moderate EEG severity group was variable and
      was not predictable from usual inspection. Frequency band analysis revealed that
      solid delta power was not significantly different among the five groups (AESD,
      MERS, FS, ES and control), and that MERS group showed the highest theta band
      power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers
      were significantly higher in the AESD group than in other groups. The alpha and
      beta band powers in EEGs within 24 h from onset were significantly lower in the
      AESD group. The band powers and their ratios showed earlier improvement towards
      24 h in FS than in AESD. CONCLUSION: Sequential EEG recording up to 24 h from
      onset appeared to be helpful for distinction of AESD from FS before emergence of
      the second phase of AESD.

PMID- 27046947
TI  - Residual Symptoms Were Differentially Associated with Brain Function in Remitted
      Patients with Major Depressive Disorders.
AB  - BACKGROUND: The desirable goals of the treatment of major depressive disorder
      (MDD) are considered both to achieve symptom remission and to help the patients
      be restored to their premorbid levels of functioning. Remission has often been
      defined clinically as a threshold using standardized scales. Such a definition,
      however, allows several residual symptoms to be present in the remitted state.
      The aim of this study was to examine the relationship between the levels of
      residual symptoms and social functioning and also the relationship between
      residual symptoms and brain function. METHODS: The subjects were 21 patients with
      MDD in remission, defined operationally using clinician-rated 17-item Hamilton
      Depression Scale. Depressive symptoms and social functioning were self-assessed
      with the Japanese versions of the Center for Epidemiologic Studies Depression
      Scale (CES-D) and the Social Adaptation Self-evaluation Scale (SASS),
      respectively. Brain function was measured by the changes in concentration of oxy
      hemoglobin ([oxy-Hb]) in the prefrontal and temporal cortices during verbal
      fluency task using near-infrared spectroscopy (NIRS). RESULTS: The mean CES-D
      total score was 18.0, s = 13.2, indicating that they have on average mild
      depression. Scores of CES-D total and those of its four factors showed a
      significantly negative correlation with the SASS total score. Among the four
      factors, "Interpersonal problems" factor showed the strongest correlation with
      it. CES-D total score and those of its three factors, "Depressed affect",
      "Somatic and retarded activity" and "Positive affect", showed significantly
      negative correlations with the mean [oxy-Hb] changes mainly in the left
      hemisphere, whereas "Interpersonal problems" factor showed a significantly
      positive correlation with the size of NIRS activation predominantly in right
      prefrontal regions. CONCLUSION: Our results indicate that remitted patients with
      MDD possibly have residual symptoms which are most likely to impair their social
      functioning and that these symptoms are differentially associated with brain
      function measured with NIRS.

PMID- 27046948
TI  - Realities and Challenges of Support for Children with Special Needs in Nursery
      Schools.
AB  - BACKGROUND: Nursery schools and kindergartens have been struggling to cope with
      increasing numbers of children with special needs. Hence, we conducted a study on
      what nursery school teachers (NSTs) will require regarding learning and societal
      resources for supporting such children in the future. METHODS: A questionnaire
      survey was conducted for 2,476 NSTs employed in 154 nursery schools in Shimane
      and Kochi Prefectures. The questionnaires were sent by post to officials at each
      nursery school. The completed questionnaires were collected by the school
      officials and returned by post. In addition to statistical processing of the
      survey results, the content of the free description responses was analyzed using
      the KJ method. RESULTS: Responses were obtained from 1,509 NSTs at 118 nursery
      schools. Of the respondents, 90.7% had experienced difficulties coping with
      children with special needs, and 83.9% were in charge of caring for such
      children. Such children were enrolled in every childcare facility participating
      in the survey. The NSTs primarily needed to learn about specific coping methods,
      the illness, and skills for supporting parents; concerning the societal
      resources, they needed the addition of assistant NSTs, the implementation of age
      five check-up, and the recruitment of mentors. The free description responses
      were categorized into the following five categories: demand for child care
      administration, cooperation with professional staff, support for parents,
      developmental health checkups, and on-site needs for nursery childcare. One of
      the specific demands was to develop human resources capable of providing parents
      with appropriate advice. CONCLUSION: The results have shown that all NSTs are
      required to deal with children with special needs. Future challenges for
      providing support for such children are: i) to raise awareness of such children;
      ii) to eliminate regional disparities; iii) to provide professional training for
      NSTs specializing in developmental disorders; iv) to train and re-educate
      assistant NSTs and v) to enhance infant screening.

PMID- 27046949
TI  - Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis
      in Rats.
AB  - BACKGROUND: Geraniol is a plant-derived phytochemical possessing anti-cancer
      action. The anti-carcinogenic effect of geraniol was investigated in the
      diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. METHODS: Male
      Wistar rats were intraperitoneally injected with 300 MUL of phosphate-buffered
      saline (PBS) (G1; n = 4) or DEN (100 mg/kg body weight) dissolved in PBS (G2; n =
      8) every 2 weeks on experimental weeks 2, 4 and 6. The rats were treated with a
      low concentration (0.07%) of geraniol (G3; n = 9) and high concentration (0.35%)
      of geraniol (G4; n = 7) for 12 weeks. To evaluate the effects of geraniol on the
      DEN-induced hepatocarcinogenesis, we compared the relative liver weight, serum
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
      phosphatase (ALP) levels and expression levels of proliferating cell nuclear
      antigen (PCNA) and glutathione S transferase-P (GST-P) by immunohistochemical
      analyses among each group. RESULTS: Relative liver weight was significantly
      higher in G2 than in G1 (P < 0.01). Both serum AST and ALT levels were
      significantly higher in G2 than in G3 and in G4 (P < 0.05). Serum ALP levels did
      not show a significant difference among each group. Percentages of both PCNA- and
      GST-P- positive area were significantly decreased in G3 and in G4 compared to in
      G2 (P < 0.001, respectively), suggesting anti-hepatocarcinogenic effects of
      geraniol. CONCLUSION: Geraniol is a promising compound useful for suppression of
      hepatocellular carcinoma. The mechanisms of action are required to be clarified
      in the future intensive study.

PMID- 27046950
TI  - Associations between Systemic Markers of Bone Turnover or Bone Mineral Density
      and Anti-Resorptive Agent-Related Osteonecrosis of the Jaw in Patients Treated
      with Anti-Resorptive Agents.
AB  - BACKGROUND: Some previous studies have examined anti-resorptive agent-related
      osteonecrosis of the jaw (ARONJ) prediction using systemic markers of bone
      turnover as risk factors. Radiographic imaging is also effective at detecting
      ARONJ. In this study, computed tomography (CT)-derived bone mineral density (BMD)
      values and the levels of systemic markers of bone turnover were evaluated, and
      then each parameter was compared between patients that developed ARONJ and those
      who did not after treatment with systemic anti-resorptive agents. The aim of this
      study was to determine whether systemic markers of bone turnover and/or BMD
      values can be used to predict the risk of ARONJ. METHODS: The subjects' serum
      levels of cross-linked N-terminal telopeptide of type I collagen (NTX) and bone
      alkaline phosphatase (BAP) (systemic markers of bone turnover) were measured. BMD
      was calibrated to CT values using a medical imaging phantom. Then, the subjects'
      BMD were assessed using quantitative computed tomography. Fifty-six patients who
      had received systemic anti-resorptive agents were included in this study. Thirty
      two of the patients developed ARONJ after receiving the drugs whereas the
      remaining 24 did not. RESULTS: No correlation was observed between the serum
      levels of the systemic markers of bone turnover and the incidence of ARONJ. On
      the other hand, the ARONJ patients exhibited higher mandibular BMD values than
      the control group. BMD was not associated with healing or the clinical stage of
      ARONJ. CONCLUSION: These results suggest that increased mandibular BMD values are
      associated with ARONJ. Furthermore, mandibular BMD might serve as a novel marker
      for predicting the risk of ARONJ in patients that are taking anti-resorptive
      agents and are about to undergo tooth extraction. Accordingly, mandibular BMD
      could be a useful tool for aiding risk assessments and guiding treatment
      decisions.

PMID- 27046951
TI  - Skipping Breakfast and Risk of Mortality from Cancer, Circulatory Diseases and
      All Causes: Findings from the Japan Collaborative Cohort Study.
AB  - BACKGROUND: Breakfast eating habits are a dietary pattern marker and appear to be
      a useful predictor of a healthy lifestyle. Many studies have reported the
      unhealthy effects of skipping breakfast. However, there are few studies on the
      association between skipping breakfast and mortality. In the present study, we
      examined the association between skipping breakfast and mortality from cancer,
      circulatory diseases and all causes using data from a large-scale cohort study,
      the Japan Collaborative Cohort Study (JACC) Study. METHODS: A cohort study of
      34,128 men and 49,282 women aged 40-79 years was conducted, to explore the
      association between lifestyle and cancer in Japan. Participants completed a
      baseline survey during 1988 to 1990 and were followed until the end of 2009. We
      classified participants into two groups according to dietary habits with respect
      to eating or skipping breakfast and carried out intergroup comparisons of
      lifestyle. Multivariate analysis was performed using the Cox proportional hazard
      regression model. RESULTS: There were 5,768 deaths from cancer and 5,133 cases of
      death owing to circulatory diseases and 17,112 cases for all causes of mortality
      during the median 19.4 years follow-up. Skipping breakfast was related to
      unhealthy lifestyle habits. After adjusting for confounding factors, skipping
      breakfast significantly increased the risk of mortality from circulatory diseases
      [hazard ratio (HR) = 1.42] and all causes (HR = 1.43) in men and all causes
      mortality (HR = 1.34) in women. CONCLUSION: Our findings showed that skipping
      breakfast is associated with increasing risk of mortality from circulatory
      diseases and all causes among men and all causes mortality among women in Japan.

PMID- 27046952
TI  - In Vitro Inhibition of Cytopathic Effect of Influenza Virus and Human
      Immunodeficiency Virus by Bamboo Leaf Extract Solution and Sodium Copper
      Chlorophyllin.
AB  - BACKGROUND: Although the link between oral and oropharyngeal health status and
      susceptibility to infection has long been recognized, there is a limit to the
      selection of antiseptics for oral care. METHODS: Madin-Darby canine kidney (MDCK)
      cells were exposed to influenza virus and cultured in the presence or absence of
      test reagents: bamboo leaf extract solution and sodium copper chrolophyllin. MDCK
      cells were pre-incubated with the reagents to assess the inhibitory activity at
      adsorption (viral attachment). Similarly, anti-HIV activity and the inhibitory
      mechanism at adsorption were assessed by MT-2 cell culture system. Mixture of HIV
      and bamboo leaf extract solution was fixed and examined by transmission electron
      microscopy. RESULTS: The 50% inhibitory concentration (IC50) of bamboo leaf
      extract solution against influenza virus and the 50% cytotoxic concentration
      (CC50) in MDCK cells of the solution lay between 0.0313-0.0625% and 0.5-1.0%. The
      solution inhibited the influenza virus adsorption at the concentration of 0.5% (P
      < 0.05). The values of IC50 and CC50 of sodium copper chlorophyllin lay between
      50-100 uM and 200-400 uM, respectively. This inhibited the virus adsorption at
      200 uM (P < 0.05). The bamboo leaf extract solution showed values of IC50 against
      HIV and CC50 in MT-2 cells at around 0.0313% and between 0.25-0.5%, respectively.
      This solution inhibited HIV adsorption at 1.25% (P < 0.05). The IC50 and CC50 of
      sodium copper chlorophyllin lay between 50-100 uM and 200-400 uM, respectively.
      Sodium copper chlorophyllin inhibited HIV adsorption at 2.5 mM (P < 0.05). HIV
      particles survived after the exposure to 0.5% bamboo leaf extract solution.
      CONCLUSION: Sodium copper chlorophyllin exerted antiviral activities against
      influenza virus and HIV as the major ingredient of bamboo leaf extract solution
      by blocking adsorption. This mechanism of action is different completely from the
      one of povidone-iodine.

PMID- 27046953
TI  - Components of Boiogito Suppress the Progression of Hypercholesterolemia and Fatty
      Liver Induced by High-Cholesterol Diet in Rats.
AB  - BACKGROUND: Ogi, one main component of boiogito (BOT), is reported to have an
      effect on hypercholesterolemia and NAFLD. In this experiment, we examined effects
      of ogi on the progression of hypercholesterolemia and fatty liver induced by high
      cholesterol diet in rats and compared with the effects of ogi combined with
      ginger or hesperidin. METHODS: Hypercholesterolemia and fatty liver were induced
      by a high cholesterol diet in rats. Extract of ogi, ogi with hesperidin, and ogi
      with ginger were added to the high-cholesterol diet, respectively. Ezetimibe was
      also added to the high-cholesterol diet as a positive control. After 6 and 12
      weeks, body, liver and adipose tissue weights, blood chemistry, lipid-related and
      inflammatory-related factors were examined. RESULTS: The high cholesterol diet
      increased body, liver and adipose tissue weights, and serum cholesterol
      concentrations. Ogi, ogi with hesperidin or ginger and ezetimibe improved them.
      In the histological examinations, we observed a significant improvement after
      treatment. The lipid-related factors (RBP4, HFABP and CFABP) were improved by
      treatment. Biomarkers of cholesterol synthesis (lathosterol) and absorption
      (campesterol, beta-sitosterol) were lower in the treatment groups. Inflammatory
      related factors (MCP1, CCR2 and TNF-alpha) and ICAM-1 were ameliorated after
      treatment, especially by ogi with ginger. CONCLUSION: Ogi, ogi with hesperidin or
      ginger have a similar effect of BOT and ezetimibe on hypercholesterolemia and
      fatty liver. Ogi with ginger reveals a stronger additive effect with no
      significant difference. However, as for the anti-inflammatory (MCP1, CCR2 and TNF
      alpha) and anti-arteriosclerotic (ICAM-1) effects, additive effects of ogi with
      ginger are more potent than that of ogi alone or ezetimibe.

PMID- 27046954
TI  - A Qualitative Study of Confusing Experiences among Japanese Adult Patients with
      Type 1 Diabetes.
AB  - BACKGROUND: In this study, we investigated the powerlessness of patients with
      type 1 diabetes (T1D), and described the structure of powerlessness that these
      individuals experienced. In order for patients to recover from this state, we
      recommend that they take steps to regain their power. METHODS: Fifteen Japanese
      adults with T1D participated in this study. Data were collected from all subjects
      between July 2013 and March 2014 via in-depth semi-structured interviews.
      Qualitative data analysis was conducted according to a grounded theory approach.
      Finally, the core category was identified, which allowed us to build a new
      powerlessness structure for T1D. RESULTS: The results suggested a core category,
      'Wandering a tangled path,' comprising four categories, eight subcategories, and
      twenty-six concepts. These four categories were as follows: 'being burdened by
      T1D,' 'suffering from insulin-related troubles,' 'being unable to cope with
      difficulties in self-management,' and 'facing social prejudice.' In the state of
      powerlessness, negative emotional experiences snowballed, with patients feeling
      more and more depressed until they ultimately reached 'rock bottom.' CONCLUSION:
      We found that as negative emotional experiences related to powerlessness
      increased, negative feelings intensified until the patients reached rock bottom.
      Powerlessness is like 'wandering a tangled path,' a state in which T1D patients
      struggle to cope with reality on their own when faced with both internal and
      external events. 'Wandering a tangled path' is at the core of powerlessness. A
      primary characteristic of the structure of powerlessness is suffering from
      confusing experiences. To help patients cope with T1D without being crushed by
      powerlessness, nurses must pay attention to signs of powerlessness. Powerlessness
      is not just an emotional state, but a combination of feelings, perceptions, and
      thoughts; therefore, it is important to comprehensively understand patients'
      narratives.

PMID- 27046955
TI  - Approximate Entropy of Respiratory Movements in Human Newborns during Different
      Sleep States.
AB  - Previous studies have reported that the respiratory cycle of healthy newborns is
      more irregular during active sleep. This study aimed to apply non-linear analysis
      to examine the irregularity of respiratory movement in newborns at different
      sleep states. The respiratory movement signals from an abdominal band during
      quiet and active sleep were analyzed using approximate entropy (ApEn). The
      breathing interval of active sleep was significantly shorter than that of quiet
      sleep [1.30 (0.17) s vs. 1.58 (0.11) s; (P < 0.03)]. The ApEn of respiratory
      movements during active sleep were significantly larger than that during quiet
      sleep [0.785 (0.135) s vs. 0.678 (0.083) s; (P < 0.05)]. We found that the ApEn
      of respiratory movement in healthy newborns could detect irregularities in
      respiration during sleep. 

PMID- 27046956
TI  - On the Relation of Setting and Early-Age Strength Development to Porosity and
      Hydration in Cement-Based Materials.
AB  - Previous research has demonstrated a linear relationship between compressive
      strength (mortar cubes and concrete cylinders) and cumulative heat release
      normalized per unit volume of (mixing) water for a wide variety of cement-based
      mixtures at ages of 1 d and beyond. This paper utilizes concurrent ultrasonic
      reflection and calorimetry measurements to further explore this relationship from
      the time of specimen casting to 3 d. The ultrasonic measurements permit a
      continuous evaluation of thickening, setting, and strength development during
      this time period for comparison with the ongoing chemical reactions, as
      characterized by isothermal calorimetry measurements. Initially, the ultrasonic
      strength-heat release relation depends strongly on water-to-cement ratio, as well
      as admixture additions, with no universal behavior. Still, each individual
      strength-heat release curve is consistent with a percolation-based view of the
      cement setting process. However, beyond about 8 h for the systems investigated in
      the present study, the various strength-heat release curves merge towards a
      single relationship that broadly characterizes the development of strength as a
      function of heat released (fractional space filled), demonstrating that mortar
      and/or concrete strength at early ages can be effectively monitored using either
      ultrasonic or calorimetry measurements on small paste or mortar specimens.

PMID- 27046957
TI  - Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce
      Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis.
AB  - This study aims to determine whether the combined blockade of IL-1beta and TNF
      alpha can alleviate the pathological allergic inflammatory reaction in the nasal
      mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea
      pigs treated with saline were used as the healthy controls. The AR guinea pigs
      were randomly divided into (1) the AR model group treated with intranasal saline;
      (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-alpha IgY
      treatment group; (4) the 0.1% anti-IL-1beta IgY treatment group; (5) the 0.1%
      combined anti-IL-1beta and TNF-alpha IgY treatment group; and (6) the fluticasone
      propionate treatment group. The inflammatory cells were evaluated using Wright's
      staining. Histopathology was examined using hematoxylin-eosin staining. The
      results showed that the number of eosinophils was significantly decreased in the
      peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P <
      0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were
      significantly reduced or absent in the nasal mucosa and lung tissues (P < 0.05)
      in the combined 0.1% anti-IL-1beta- and TNF-alpha IgY-treated guinea pigs. The
      data suggest that topical blockade of IL-1beta and TNF-alpha could reduce
      pathological allergic inflammation in the nasal mucosa and lung tissues in AR
      guinea pigs. 

PMID- 27046958
TI  - Primum Non Nocere.
AB  - Surgical ovarian wedge resection was the first established treatment for women
      with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both
      due to the risk of postsurgical adhesions and the introduction of medical
      ovulation induction. Laparoscopic ovarian drilling (LOD) is an alternative method
      to induce ovulation in PCOS patients with clomiphene citrate resistance instead
      of gonadotropins. Surgical therapy with LOD may avoid or reduce the need for
      gonadotropins or may facilitate their use. However, the procedure, though
      effective, can be traumatic on the ovaries, which may cause postoperative
      adhesions and/or diminished ovarian reserve. In over-enthusiastic hands, this day
      care procedure might lead to iatrogenic premature ovarian failure in young women.
      Some trials have compared LOD with gonadotropins, but, because of variations in
      study design and small sample size, the results are inconsistent and definitive
      conclusions about the relative efficacy of LOD and gonadotropins cannot be
      extracted from the individual studies. Today, evidence-based reviews conclude
      that there is no evidence of a significant difference in rates of clinical
      pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS
      undergoing LOD compared to other medical treatments. The reduction in multiple
      pregnancy rates in women undergoing LOD is the only pro-LOD argument. However,
      there are ongoing serious concerns about the long-term effects of LOD on ovarian
      function. 

PMID- 27046959
TI  - Influenza Vaccine Requirements in Pregnant Women.
AB  - OBJECTIVE: To explore the importance of administering influenza vaccine during
      pregnancy. MATERIALS AND METHODS: An internet search for data, study and position
      papers was done. Medline and Pubmed were the frequently used search engines
      besides search for WHO and CDC position statements. The keywords used included,
      influenza vaccine, pregnancy, outcome, safety and trimesters. RESULTS: Search
      provided studies that had been conducted in developing nations like Bangladesh as
      well as developed nations like Norway and England. The WHO and CDC status reports
      were also accessed and studied. CONCLUSION: Administration of influenza vaccine
      is recommended in any trimester of pregnancy, to protect the pregnant woman as
      well as the newborn child below the age of 6 months from the deleterious effects
      of influenza. The vaccine is safe and free from side effects.

PMID- 27046960
TI  - Polycystic Ovarian Syndrome: Is It Time to Rename PCOS to HA-PODS?
AB  - The term polycystic ovarian syndrome (PCOS) came into existence 80 years ago.
      Pathophysiology of PCOS remains ill understood despite extensive research in this
      field. It is now accepted that the manifestations of PCOS are not confined to the
      reproductive dysfunction, and there are endocrine-metabolic implications to PCOS
      with several consequences to female health. PCOS is a misnomer as ovaries do not
      contain epithelial cysts, but they are actually antral follicles. Moreover, the
      name PCOS neither reflects the hyperandrogenism which is essential for diagnosis
      nor the metabolic derangements. While various authors have expressed the need for
      change of the name, a suitable new option has not yet been established. This
      review aims to analyse the current understanding of pathophysiology of PCOS and
      addresses to the controversies associated with its diagnosis and nomenclature.
      The name "Hyperandrogenic Persistent Ovulatory Dysfunction Syndrome or HA-PODS"
      is proposed here to overcome diagnostic pitfalls of previous nomenclature. This
      new name will help formulate appropriate treatment and promote consistency in
      research as well. Further categorizations of HA-PODS are also discussed in the
      article. 

PMID- 27046961
TI  - Early Teenage Pregnancy: Is it Safe?
AB  - AIM: To compare obstetric and perinatal outcomes of early and late teenage
      pregnancies of Omani nulliparous women with singleton pregnancies cared for and
      delivered at a tertiary teaching hospital. METHOD: In this retrospective study,
      we reviewed obstetric and perinatal outcomes of early teenage pregnancies (14-16
      years), (n = 20) delivered at Sultan Qaboos University Hospital, Muscat, Oman,
      between 1 July 2006 and 30 June 2013 and compared their outcomes with outcomes of
      late teenage pregnancies (17-19 years), (n = 287) delivered at the same hospital
      during same period. RESULTS: When compared with late teenage pregnant women,
      early teenagers were found to have no significant differences in prevalence of
      very preterm delivery <32 weeks (P = 0.62), preterm rupture of membranes (P = >
      0.99), and anemia (P = 0.34). When compared to late teenagers, early teenagers
      had similar cesarean sections rates (P = >0.99), instrumental delivery rates (P =
      0.56) and spontaneous vaginal delivery rates (P > 0.99). Both groups had similar
      birth weights (P = 0.87), low birth weights, (P = 0.55), and very low birth
      weights babies (P = 0.56 %). Perinatal mortality rate was similar in both groups.
      CONCLUSION: We may conclude that early teenage pregnant Omani women are not at
      increased risk of obstetric and perinatal complication compared to older
      teenagers.

PMID- 27046962
TI  - Current Scenario of Vitamin D Status During Pregnancy in North Indian Population.
AB  - PURPOSE OF THE STUDY: The aim of the study was to determine the prevalence and
      risk factor for vitamin D deficiency in our pregnant population. METHOD: A total
      of 418 healthy primigravida with single live pregnancy and sure of dates
      attending the antenatal clinic between October 2011 and April 2013 were
      recruited. Women were excluded if they had history of current or past chronic
      medical disease. Women were also excluded if they had history of medication with
      drugs interfering with calcium and vitamin D metabolism. RESULTS: The prevalence
      of vitamin D deficiency during pregnancy has been found to be 391 (93.5 %).
      Severe vitamin D deficiency among pregnant patients was 34.44 % (144/418). The
      levels of serum 25(OH)D and serum calcium were significantly lower in severe
      deficient group than the adequate group [7.10 +/- 1.49 vs. 38.90 +/- 4.22 ng/ml
      (p = 0.001) and 7.13 +/- 1.41 vs. 9.39 +/- 0.88 ng/ml (p = 0.001)], respectively.
      Maternal education, husband education, socioeconomic status, serum calcium, serum
      phosphorous, and season were significant factors associated with vitamin D
      deficiency. Significant independent variables for severe vitamin D deficiency
      were low serum calcium, serum alkaline phosphatase, and serum phosphorus (OR
      39.41, 95 % CI 10.30-150.85, p < 0.01), (OR 18.03, 95 % CI 3.95-82.44, p < 0.01),
      and (OR 8.40, 95 % CI 2.47-28.61, p < 0.01). CONCLUSION: Vitamin D deficiency is
      highly prevalent among pregnant women in Northern India, and these raises concern
      about the health consequences for the mother and the offspring.

PMID- 27046963
TI  - Chemical Shift Artifact on Steady-State MRI Sequences for Detection of Vesical
      Wall Invasion in Placenta Percreta.
AB  - BACKGROUND: Antenatal diagnosis of the invasiveness of a placenta percreta helps
      in planning the surgical approach, reducing blood loss and morbidity. Doppler
      sonography is the mainstay diagnostic modality with a sensitivity of 80-95 %.
      With the advent of high magnetic field MRI techniques, there has been recent
      interest in evaluation of placenta by MRI. On an extensive PUBMED search, we
      could not find any citations describing imaging, ultrasound, or MRI features to
      evaluate vesical wall invasion by placenta percreta. PURPOSE: We attempt to
      evaluate transmyometrial vesical wall invasion by placenta percreta using
      chemical shift artifact as a marker of intact bladder-myometrial interface on
      steady-state MRI sequences. MATERIALS AND METHODS: This is a prospective
      observational study, conducted at a university hospital. We have compiled clinico
      radiological criteria for diagnosis of invasive placentae based on the existing
      body of evidences, in four patients. We further go on to analyze a specific
      proposed sign on a newly introduced MR imaging sequence i.e., loss of chemical
      shift artifact (India ink line) on steady-state GRE sequence (TrueFISP), to
      diagnose transmyometrial vesical invasion in placenta percreta. RESULTS: Though
      the sample size is small, the sensitivity, specificity, positive, and negative
      predictive value of the proposed sign for the purpose was 100 %. CONCLUSIONSS:
      Loss of chemical shift artifact (India ink line) on steady-state GRE sequences at
      the vesico-myometrial junction in case of invasive placentae confirms vesical
      wall invasion, a prospective diagnoses of which can help in planning the surgical
      protocol and preventing potentially fatal blood loss.

PMID- 27046964
TI  - Evaluation of Preoperative Serum Levels of CA 125 and Expression of p53 in
      Ovarian Neoplasms: A Prospective Clinicopathological Study in a Tertiary Care
      Hospital.
AB  - OBJECTIVES: To assess the preoperative serum levels of CA 125 with its diagnostic
      role and to evaluate the p53 expression in patients of primary ovarian neoplasms.
      We also wished to judge their relationship with other parameters like clinical
      staging and histopathologic tumor type. MATERIALS AND METHODS: The present study
      was conducted on 86 patients during the study period of 2.5 years. Preoperative
      CA 125 levels were evaluated by an automated immunoassay analyzer. p53 expression
      was judged immunohistochemically with pre-diluted monoclonal antibody. An
      objective scoring was done depending on distinct nuclear immunopositivity.
      RESULTS: Median value of preoperative CA 125 levels was 32 U/mL in benign surface
      epithelial-stromal tumors (BSEST), 53 U/mL in borderline surface epithelial
      stromal tumors (BOT), 346 U/mL in malignant surface epithelial-stromal tumors
      (MSEST) and 560 U/mL in serous adenocarcinomas (SAC). Most of ovarian tumors were
      in the FIGO stage I (64 cases, 74.4%), but higher stages (II, III, IV) were
      observed mostly in MSESTs. SACs displayed the maximum p53 expression. Considering
      the cut-off value of more than 35 U/mL in CA 125 levels, the sensitivity to
      diagnose MSESTs was 94.7%. Preoperative CA 125 levels strongly and positively
      correlated with FIGO staging and p53 expression. Similarly p53 expression
      strongly and positively correlated with FIGO staging and histopathological
      categories. CONCLUSION: Higher values of preoperative CA 125 levels and higher
      expression p53 are associated with MSESTs and BOTs especially of serous type.
      They strongly correlate with each other and with tumor stage. But there is no
      serum CA 125 concentration that can clearly differentiate benign and malignant
      ovarian masses.

PMID- 27046965
TI  - Role of Thyroid Dysfunction in Patients with Menstrual Disorders in Tertiary Care
      Center of Walled City of Delhi.
AB  - OBJECTIVE: To study the prevalence of thyroid disorders and its correlation with
      menstrual disorders. METHODS: 100 women aged between 15 and 45 years who attended
      gyne OPD in Kasturba Hospital, Delhi, were included for this cross-sectional
      study. The study group comprised 50 patients presented with menstrual complaints.
      The control group consisted of 50 women of same age group with complaints other
      than menstrual disorders. Thyroid function tests, anti-TPO antibody estimation,
      and endometrial sampling were done in all patients. RESULTS: In patients with
      menstrual disorders, 44 % had thyroid disorders in which subclinical
      hypothyroidism was prevalent in 20 %, overt hypothyroidism in 14 %, and overt
      hyperthyroidism in 8 % of the women. Autoimmune thyroid antibodies were present
      in 30 % patients of women with menstrual disorders. On endometrial sampling,
      hypothyroid patients mainly had proliferative endometrium (42.85 %) whereas
      hyperthyroid had atrophic endometrium (60 %). CONCLUSIONS: Thyroid dysfunction is
      an important causative etiology of menstrual abnormalities. Assessment of thyroid
      function should be done in all patients with menstrual disorders to avoid
      unnecessary interventions like curettage and hysterectomy.

PMID- 27046966
TI  - Gestational Trophoblastic Neoplasia: Challenges Dealt in the Diagnosis.

PMID- 27046967
TI  - Spinal Epidural Abscess with Pregnancy Leading to Paraplegia.

PMID- 27046968
TI  - Primary Non-Hodgkins Lymphoma of Uterine Cervix: A Case Report of Two Patients.

PMID- 27046969
TI  - Herlyn-Werner-Wunderlich Syndrome.

PMID- 27046970
TI  - Critical Ovarian Hyperstimulation Syndrome and Management.

PMID- 27046971
TI  - Mangeshikar Uterine Manipulator.

PMID- 27046972
TI  - Pediatric surgery in India - The way forward.

PMID- 27046974
TI  - Video teaching program on management of colostomy: Evaluation of its impact on
      caregivers.
AB  - CONTEXT: Care of a child having colostomy has not been institutionalized for a
      long time for economic and administrative reasons. After stoma formation, stoma
      care has to be provided to the child by caregivers at home. Hence, caregivers
      need to be provided with ongoing education and support, commencing from
      preoperative teaching to discharge from the hospital and home care. AIMS: The
      aims of this study were to develop video-based learning resource material and to
      evaluate its effectiveness in terms of knowledge and skill attainment by
      caregivers. SETTINGS AND DESIGN: The study design was time series, one group
      pretest and post test. This was conducted among 30 caregivers attending pediatric
      surgery outpatients and indoor departments of a tertiary level care center.
      MATERIALS AND METHODS: A video teaching program (VTP) related to pediatric
      colostomy was developed and used to teach the caregivers about colostomy care.
      Pretested and validated knowledge questionnaire, observational checklist, and
      stoma assessment scale (SAS) were used to assess the knowledge and skills of
      caregivers before and after the administration of VTP immediately (post test 1)
      after and 2 weeks (post test 2) after the intervention. STATISTICAL ANALYSIS
      USED: Repeated measures analysis of variance (ANOVA), Bonferroni correction, Mann
      Whitney U test, and Kruskal-Wallis test were used. RESULTS: There were
      significant increases in knowledge (from 10.9 +/- 2.5 to 16.4 +/- 1.67 and 15.9
      +/- 4.02, P = 0.001, maximum score 20) and skill scores as assessed by the
      observation checklist (from 5.6 +/- 2.0 to 9.8 +/- 1.6 and 8.6 +/- 2.1, P =
      0.001, maximum score 12) immediately after and 2 weeks after the VTP. However, a
      decline in skills was observed at 2 weeks when compared with immediate scores, as
      measured by the observation checklist. There was no significant increase in the
      skill scores of caregivers as measured by SAS at 2 weeks compared to the
      immediate scores. CONCLUSION: The VTP was effective in bringing about an increase
      in the knowledge and skill of caregivers of children having colostomy. Therefore,
      video can be utilized for the counselling of caregivers of children with
      colostomy.

PMID- 27046973
TI  - Portal pressure and blood nitric oxide levels as predictors of outcome in biliary
      atresia.
AB  - AIM: To evaluate the incidence of portal hypertension (PHT) in biliary atresia
      (BA) patients and to monitor its progress after Kasai portoenterostomy (KP) by
      measuring nitric oxide (NO) levels in peripheral blood. MATERIALS AND METHODS: A
      prospective cross-sectional study conducted over a period of 2 years.
      Intraoperative portal pressure (PP) and blood NO levels at presentation, 1-month,
      3-month, and 6-month follow-up, were correlated with clinical and biochemical
      parameters in BA patients. The mean NO level in age-matched control group was
      4.64 +/- 2.32 MUmol/L. RESULTS: Thirty-four BA patients underwent KP over a
      period of 2 years. The mean age of presentation was 2.7 months (range 1-4
      months). The mean intraoperative PP was 21.3 +/- 5.4 mmHg. The mean PP in
      patients aged <60 days, 61-90 days, and >90 days was 18.53 +/- 4.45 mmHg, 20.33
      +/- 3.07 mmHg, and 26.5 +/- 5.01 mmHg, respectively. The mean PP in the patients
      who underwent successful KP was 16.75 +/- 3.54 mmHg while for those who continued
      to have jaundice it was 23.94 +/- 4.63 mmHg (P < 0.001). NO levels closely
      followed the PP as shown by the regression equation NO = 4.79 + 0.64 PP mmHg, R
      (2) = 0.69. The mean NO level at presentation was 18.48 +/- 4.17 MUmol/L and at 1
      month, 3-month, and 6-month follow-up was 11.94 +/- 5.62 MUmol/L, 10.79 +/- 6.02
      MUmol/L, and 9.93 +/- 6.53 MUmol/L, respectively (P < 0.001). The difference in
      NO levels was also statistically significant between the patients who cleared
      jaundice and those with persisting jaundice. CONCLUSION: All BA patients had PHT
      at presentation. PHT worsens with age and has an adverse effect on outcome of KP.
      NO levels in blood closely follow PP and higher levels are associated with poor
      outcome.

PMID- 27046975
TI  - The fate of facial asymmetry after surgery for "muscular torticollis" in early
      childhood.
AB  - AIMS AND OBJECTIVES: To study wheather the facial features return to normal after
      surgery for muscular torticollis done in early childhood. MATERIALS AND METHODS:
      This is a long-term study of the fate of facial asymmetry in four children who
      have undergone operation for muscular torticollis in early childhood. All the
      patients presented late, i.e., after the age of 4 years with a scarred
      sternomastoid and plagiocephaly, so conservative management with physiotherapy
      was not considered. All the patients had an x-ray of cervical spine and eye and
      dental checkup before making a diagnosis of muscular torticollis. Preoperative
      photograph of the patient's face was taken to counsel the parents about the
      secondary effect of short sternomastoid on facial features and the need for
      surgery. After division of sternomastoid muscle and release of cervical fascia
      when indicated, the head was maintained in a hyperextended position supported by
      sand bags for three days. Gradual physiotherapy was then started followed by
      wearing of a Minerva collar that the child wore for a maximum period of time in
      24 h. Physiotherapy was continued three times a day till the range of movements
      of the head returned to normal. During the follow-up, serial photographs were
      taken to note the changes in the facial features. RESULTS: In all four patients,
      the asymmetry of the face got corrected and the facial features returned to
      normal. CONCLUSION: Most of the deformity of facial asymmetry gets corrected in
      the first two years after surgery. By adolescence, the face returns to normal.

PMID- 27046976
TI  - Uncommon renal tumors in children: A single center experience.
AB  - AIMS: Scrutiny over the clinical behaviors, management, and the final outcome of
      some rare renal neoplasm in order to find out some hidden facts about these
      tumors which are playing an important role in the disease course and its
      management. MATERIALS AND METHODS: Retrospective evaluation of uncommon (non
      Wilms') renal neoplasm in the pediatric population in a tertiary care center.
      Fifteen cases of uncommon renal tumors were treated in our institution over the
      last 5 years (January 2008 to December 2012). The cases were tabulated in the
      form of age, sex, mode of presentation, preoperative investigations,
      intraoperative grading, pathological type, postoperative management and the final
      outcome. The patients were followed up for 2 years (clinically every 3 months and
      ultrasonography abdomen in every 6 months for first 2 years) in order to see any
      evidence of recurrence and complications related to postoperative chemotherapy.
      RESULTS: Out of 15 cases, four cases were clear cell sarcoma (CCS) (26.6%), three
      cases were rhabdoid tumor (20%), three cases were congenital mesoblastic nephroma
      (20%), two cases were multilocular cystic nephroma (13.3%), two cases were renal
      teratoma (13.3%), and one case of teratoid Wilms' tumor (6.6%). There were two
      deaths (one CCS and one rhabdoid tumor) due to chemotherapy-related toxicity but
      no recurrence. Three patients were lost during postoperative follow-up; ten
      patients are doing well and getting a regular visit in the follow-up clinic.
      CONCLUSION: The clinical presentations of these uncommon renal tumors are similar
      to that of Wilms' tumor. Thus, preoperative diagnosis is difficult even with
      modern imaging techniques. Some of these tumors (CCS, rhabdoid tumor) are rapidly
      progressing and have a poor outcome. Hence, early intervention in the form of
      complete surgical resection of the tumor (whenever possible) and postoperative
      chemo/radiotherapy are imperative for fruitful outcome.

PMID- 27046977
TI  - The extended Kasai portoenterostomy for biliary atresia: A preliminary report.
AB  - AIMS: In 1955, Professor Morio Kasai first performed a hepatic portoenterostomy.
      Since then, the procedure has changed the lives of children with biliary atresia
      (BA). We report our initial experience in performing "extended" Kasai
      portoenterostomy (KPE), a modification of the original procedure. MATERIALS AND
      METHODS: Since 2013, we have used the technique of "extended KPE" and
      prospectively recorded data on all children undergoing this operation. Data on
      demographics, clinical features, liver function tests, and perioperative
      cholangiogram findings were collected. Outcome of KPE was measured by Jaundice
      Disappearance Rate (JDR) and Native Liver Survival Rate (NLSR). We present our
      preliminary results from a 30-month period (February 2013 to May 2015). RESULTS:
      Thirty-one children underwent KPE during this period (19 males) and only 1 child
      had biliary atresia splenic malformation (BASM). The mean age at KPE was 73 +/-
      24 days. Five (16.1%) children were more than 90 days old at the time of KPE.
      Fourteen children cleared jaundice (JDR 45.2%). Eleven (35.5%) children developed
      episodes of cholangitis, of whom 8 had early cholangitis (within 3 months of the
      operation). The proportion of children who survived with their own liver 6 months
      after KPE (NLSR) was 84.2%. Of those children older than 90 days, 2 cleared
      jaundice and have survived with their native livers for more than 16 months.
      CONCLUSION: In our preliminary report of 31 children, we conclude that the
      extended KPE leads to increased jaundice clearance and improved NLSR in children
      with BA.

PMID- 27046978
TI  - Giant congenital solitary nonparasitic cyst of the liver causing respiratory
      distress in a neonate.
AB  - A 3-day-old male neonate delivered at 34 weeks of gestational age was brought
      with breathing difficulty since birth. The abdomen was massively distended. A
      soft cystic mass was occupying almost the entire abdomen and causing obvious
      respiratory distress. On exploration, a huge, solitary, unilocular cyst was found
      between the two lobes of the liver. Growing extrahepatically between the two
      lobes, it had displaced them laterally on either side. Enucleation of the cyst
      and marsupialization of its base was done. Histopathology showed evidence of
      congenital solitary nonparasitic cyst of the liver. Symptomatic presentation of
      CSNCL in children, especially in a neonate is extremely rare and not considered
      as a differential diagnosis of an abdominal mass. Hence, the case report. 

PMID- 27046979
TI  - Synovial sarcoma of kidney in a child: A rare presentation.
AB  - There are no reported cases in the literature of primary renal synovial sarcoma
      in pediatric patients. The management of renal synovial sarcoma has been
      extrapolated from the management of soft tissue sarcomas at other sites. We
      present a 4-year-old female who was suspected to have Wilms' tumor. The patient
      underwent guided biopsy as she did not respond to neoadjuvant chemotherapy for
      Wilms' tumor. The biopsy was consistent with primary renal synovial sarcoma. The
      child was treated with change in her neoadjuvant chemotherapy regimen and
      surgery. The diagnosis of synovial sarcoma was confirmed by demonstrating the t
      (X, 18) translocation using polymerase chain reaction. 

PMID- 27046980
TI  - Complete sternal cleft - A rare congenital malformation and its repair in a 3
      month-old boy: A case report.
AB  - Complete midline sternal cleft is a rare congenital anomaly resulting from failed
      midline ventral fusion of the sternal bars. Very few cases of complete sternal
      cleft have been described in literature. We present a case of complete sternal
      cleft in a 3-month-old child. The patient underwent primary closure of the defect
      using stainless steel wires. 

PMID- 27046981
TI  - Rhabdomyosarcoma of the breast: Report of two cases with the review of
      literature.
AB  - Rhabdomyosarcoma (RMS) is a common soft-tissue neoplasm in the pediatric age
      group. Common locations are head and neck, genitourinary areas, trunk, and
      extremities. Two pathologic variants of this malignancy are embryonal and
      alveolar. The involvement of breast is rare. Herein, we report two cases of
      alveolar RMS of the breast of which one is an isolated breast metastasis from an
      orbital primary, whereas the other is a primary RMS of the breast. Both the
      patients were treated with surgery followed by adjuvant chemotherapy and
      radiotherapy and are currently disease free at six and three year respectively,
      following completion of treatment. 

PMID- 27046982
TI  - Pancreatoblastoma masquerading as hepatoblastoma: A diagnostic dilemma.
AB  - Clinicoradiological and histopathological differentiation of pancreatoblastoma
      from hepatoblastoma can often be a challenge in clinical practice owing to their
      peculiar resemblance. We report a case of a 4-year-old boy with a right
      hypochondriac region mass, which was diagnosed as hepatoblastoma on the basis of
      imaging, raised tumor marker, and biopsy; however, pancreatic origin of the mass
      was ascertained on exploration and pancreatoblastoma was confirmed on
      histopathology. 

PMID- 27046983
TI  - Delayed onset of right congenital diaphragmatic hernia associated with Group B
      streptococcal sepsis in a neonate.
AB  - A full-term male neonate was initially managed for respiratory distress which
      developed few hours after birth. His initial chest radiograph was normal, and
      blood culture revealed Group B streptococcal (GBS) sepsis. He subsequently
      developed progressive right chest opacification that did not improve with medical
      management. Imaging done few days later revealed right-sided diaphragmatic
      hernia. The 12-day-old neonate underwent primary repair of the diaphragmatic
      defect and had an uneventful recovery. This case report intends to highlight this
      unique association between early onset GBS sepsis and delayed onset of the right
      congenital diaphragmatic hernia. 

PMID- 27046984
TI  - A new anastomosis technique for intestinal diseases with proximal dilated
      segments.
AB  - A number of techniques have been described for intestinal anastomosis. We
      describe a different, simple, and safe technique that can be used in patients
      with intestinal diseases, such as jejunoileal atresia and perforation that has
      proximal dilated segments. In this technique, an atraumatic bowel clamp was
      applied on the proximal dilated bowel at a 90 degrees  angle. In the narrow
      distal segment, we resected the bowel at a 0 degrees  angle and continued at a 30
      degrees  angle from the antimesenteric side. Finally, a two-layer interrupted
      anastomosis was performed. We applied this technique to a 31-day-old patient who
      had a divided jejunostomy due to malrotation and perforation with a proximal
      dilated bowel. Neither anastomotic complications nor feeding and passage problems
      were seen postoperatively. 

PMID- 27046985
TI  - Laparoscopic ipsilateral ureteroureterostomy for the management of children with
      duplication anomalies.

PMID- 27046986
TI  - Prevalence of Campylobacter species in milk and milk products, their virulence
      gene profile and anti-bio gram.
AB  - AIM: During the last decades, number of food poisoning cases due to Campylobacter
      occurred, immensely. After poultry, raw milk acts as a second main source of
      Campylobacter. Therefore, the present study was undertaken to detect the
      prevalence of Campylobacters in milk and milk products and to know the antibiotic
      sensitivity and virulence gene profile of Campylobacter spp. in Anand city,
      Gujarat, India. MATERIAL AND METHODS: A total of 240 samples (85 buffalo milk, 65
      cow milk, 30 cheese, 30 ice-cream and 30 paneer) were collected from the
      different collection points in Anand city. The samples were processed by
      microbiological culture method, and presumptive isolates were further confirmed
      by genus and species-specific polymerase chain reaction using previously reported
      primer. The isolates were further subjected to antibiotic susceptibility assay
      and virulence gene detection. RESULT: Campylobacter species were detected in 7
      (2.91%) raw milk samples whereas none of the milk product was positive. All the
      isolate identified were Campylobacter jejuni. Most of the isolates showed
      resistance against nalidixic acid, ciprofloxacin, and tetracyclin. All the
      isolates have three virulence genes cadF, cdtB and flgR whereas only one isolate
      was positive for iamA gene and 6 isolates were positive for fla gene. CONCLUSION:
      The presence of Campylobacter in raw milk indicates that raw milk consumption is
      hazardous for human being and proper pasteurization of milk and adaptation of
      hygienic condition will be necessary to protect the consumer from this zoonotic
      pathogen.

PMID- 27046987
TI  - Seroprevalence of Mycoplasma gallisepticum antibody by ELISA and serum plate
      agglutination test of laying chicken.
AB  - AIM: Mycoplasma gallisepticum (MG) is important avian pathogens responsible for
      chronic respiratory diseases of chicken and turkeys, which result in large
      economic loss for the poultry industry. The objectives of this study were
      determination of seroprevalence of MG antibody of commercial layer chicken at
      laying period in selected areas of Bangladesh. MATERIALS AND METHODS: A total of
      563 blood samples were collected randomly from selected commercial layer chickens
      at laying period during the period from July to December, 2013. Indirect enzyme
      linked immunosorbent assay (iELISA) and serum plate agglutination (SPA) test were
      performed to detect the presence of antibodies against MG. RESULTS: Of 563
      samples, 64.47% and 56.13% showed an overall prevalence of MG antibodies in
      iELISA and SPA test respectively. Prevalence of MG was recorded the highest
      (69.63%) at 50-55 weeks of age compared with lowest (53.26%) at 56-61 weeks of
      age (p<0.05). Significant (p<0.05) effect of breed were observed in the
      seroprevalence of MG infection in layer birds in the present study. The overall,
      68.77%, 63.74% and 59.37% prevalence were found respectively in sonali, ISA Brown
      and White leg horn. The prevalence of MG antibodies was the highest (70.13%) in
      December followed by November (68%), October (65.67%), August (63.46%), September
      (58.54%) and July (51.78%) month. The seroprevalence of MG antibodies was higher
      (69.63%) in most of the large flocks and lower (56.82%) in small flocks.
      CONCLUSION: Therefore, might be suggested that the commercial layer farms should
      be routinely checked to monitor MG infection and the reactor birds should be
      culled since MG organism has the potential to transmit vertically. The
      correlation between MG antibody in month and flock size was not significant
      (p=0.359 and p=0.868, respectively).

PMID- 27046988
TI  - Effect of sugar beet tubers as a partial replacer to green fodder on production
      performance and economics of lactating Surti buffaloes in lean period.
AB  - AIM: The objective of this study was to evaluate the effects of sugar beet tubers
      as a replacer to green fodder on production performance and economics of
      lactating Surti buffaloes. MATERIALS AND METHODS: This trial was conducted at the
      Livestock Research Station, Navsari Agricultural University, Navsari. Twenty
      lactating Surti buffaloes in a changeover experimental design were selected to
      assess the effects of replacing green fodder with sugar beet (Beta vulgaris L.)
      tubers on production performance, economics of feeding sugar beet and blood
      biochemical profile. Half (50%) of the hybrid Napier was replaced with sliced
      sugar beet tubers in the ration of experimental animals. RESULTS: Partial
      replacement of hybrid Napier with that of sugar beet tubers numerically improved
      dry matter intake, milk yield, 4% fat corrected milk and milk composition
      parameters such as fat, solid non-fat, protein and lactose, but not
      significantly. The blood parameters were in normal range and non-significant
      except that of glucose and triglycerides, which were increased in the sugar beet
      group. Replacing sugar beet tubers also proved to be cost-effective with improved
      net profit around Rs. 6.63/day. CONCLUSION: It can be concluded that 50% hybrid
      Napier fodder can be replaced with sugar beet tubers without any adverse effect
      on animal production performance, milk composition blood biochemical profile and
      economics of feeding.

PMID- 27046989
TI  - Kinnow madarin (Citrus nobilis lour * Citrus deliciosa tenora) fruit waste silage
      as potential feed for small ruminants.
AB  - AIM: Study was conducted to ascertain the quality of Kinnow mandarin waste (KMW)
      silage and its utilization by adult male goats. MATERIALS AND METHODS: KMW was
      collected, dried to 30% dry matter level and ensiled in silo pit after addition
      of disodium hydrogen orthophosphate as source of phosphorus as KMW is deficient
      in phosphorus. Oat was collected at milking stage, chopped finely and ensiled in
      a silo pit for 2 months. Twelve nondescript local adult male goats of about 8-10
      months age and mean body weight of 23.00+/-0.90 kg were selected. The goats were
      randomly allotted on body weight as per randomized block design into two equal
      groups, six animals in each group (n=6) namely "oat silage (OS)" and "Kinnow
      silage." Goats were offered weighed quantities of respective silage on ad libitum
      basis. The silages were evaluated for proximate principles and silage quality
      attributes. RESULTS: Differences were found between chemical composition of both
      silages with higher organic matter, ether extracts, nitrogen free extract
      (p<0.05) and lower (p<0.01) crude fiber, neutral detergent fiber and acid
      detergent fibre concentration in KMW silage as compared to OS. However, silages
      were isonitrogenous (8.20 vs. 8.17; p>0.05 for CP) and possess comparable (2.23
      vs. 2.06; p>0.05) calcium content. The pH, ammonia nitrogen (percent of total
      nitrogen) and soluble carbohydrate content were lower (4.20 vs. 3.30; 4.14 vs.
      3.80; 2.73 vs. 1.86; p<0.05) in KMW silage, whereas, lactic acid concentration
      was higher (6.23 vs. 8.14; p<0.05) in KMW silage indicating its superior quality
      as compared to OS. Body weight (kg) of goats and silage intake (g/day), were
      comparable (p>0.05) among the two dietary groups. CONCLUSION: It can be concluded
      that KMW can be used to prepare good quality silage for feeding of goats.

PMID- 27046990
TI  - Hematobiochemical alterations and direct blood polymerase chain reaction
      detection of Theileria annulata in naturally infected crossbred cows.
AB  - AIM: The aim was to determine hemato-biochemical changes and rapid diagnosis of
      Theileria annulata in naturally infected crossbred cows. MATERIALS AND METHODS:
      Blood samples from lactating crossbred cows (n=40) between 3 and 7 years of age
      and showing clinical signs of tropical theileriosis were collected, with or
      without anticoagulant, and analyzed for tropical theileriosis by direct smear,
      direct blood polymerase chain reaction (PCR) detection of merozoite-piroplasm
      surface antigen (Tams1) gene specific amplicon, estimation of hematological and
      biochemical parameters. Healthy crossbred cows (n=6), examined free from
      hemoprotozoan infections were included as control. RESULTS: The infected
      crossbred cows revealed significantly (p<0.001) lower values of total
      erythrocytic counts (4.46+/-0.2 * 10(6)/uL), hemoglobin (Hb 6.025+/-0.39 g%),
      packed cell volume (17.05+/-1.1%), mean corpuscular volume (37.94+/-1.70 fL) and
      mean corpuscular Hb (13.5+/-0.48 pg; p<0.002) compared with healthy control. The
      serum samples of infected cows revealed profound (p<0.05) hyponatremia (Na
      133.21+/-2.36 mEq/l) and hypocalcemia (Ca 8.39+/-0.34 mg%). Infected crossbred
      cows showed a significant increase (p<0.05) of mean serum activity of alanine
      aminotransferase (61.45+/-13.36 U/L), aspartate aminotransferase (146.1+/-20.97
      U/L), blood urea nitrogen (28.26+/-3.90 mg%), creatinine (1.55+/-0.13 mg%),
      direct bilirubin (0.33+/-0.04 mg%; p<0.001) and lactate dehydrogenase (3001.32+/
      167.0 U/L; p<001). Blood direct PCR revealed a 721-bp fragment amplified from the
      target gene encoding 30-kDa major merozoite surface antigen of T. annulata using
      specific primer pairs. This assay was positive for all the infected animals.
      CONCLUSION: The assessments of hemato-biochemical parameters in T. annulata
      infected crossbred cows may be useful in understanding disease pathogenesis,
      prognosis and corrective measures for supportive therapy. Moreover, blood direct
      PCR can reliably be used for rapid detection of T. annulata in conjunction with
      microscopic examination.

PMID- 27046991
TI  - Clinicopathological studies of gastrointestinal tract disorders in sheep with
      parasitic infection.
AB  - AIM: This study was envisaged to elucidate the parasitological aspects of
      gastrointestinal tract (GIT) disorders of sheep. MATERIALS AND METHODS: Fecal,
      blood and serum samples collected from 31 sheep/lambs of Sheep Breeding Farm,
      Lala Lajpat Rai University of Veterinary & Animal Sciences, Hisar. RESULTS: Of 25
      cases, strongyle eggs (12 cases, 48%) were a major infection, followed by
      Strongyloides spp. (8 cases, 32%) and Moniezia spp. (5 case, 20%). In one case,
      massive infection of strongyle particularly Haemonchus contortus and Moniezia
      spp. was observed. All these animals were found negative for hemoprotozoan
      parasites in blood smear examination. Hematological studies revealed that
      significantly decreased values of hemoglobin (Hb), packed cell volume (PCV) and
      total erythrocytic count (TEC). Absolute leukocytic count revealed significant
      leukocytosis due to neutrophilia, lymphocytosis, monocytosis and eosinophilia.
      Serum biochemical profiles of diarrheic sheep/lambs in present study were
      significant decrease in values of total protein, serum globulin, glucose where as
      significant increase in the albumin: Globulin ratio, aspartate aminotransaminase
      (AST), alanine aminotransaminase (ALT), alkaline phosphatise (ALKP) and
      bilirubin. CONCLUSIONS: From the present study, it is reasonable to conclude that
      major parasitic infection of sheep/lamb observed was strongyle, followed by
      Strongyloides spp. and Moniezia spp. Hemato-biochemical studies revealed
      significant leukocytosis and increase in AST, ALT, ALKP and bilirubin.

PMID- 27046992
TI  - Epidemiological study of canine parvovirus infection in and around Bhubaneswar,
      Odisha, India.
AB  - AIM: An epidemiological study of canine parvovirus infection in dogs in and
      around Bhubaneswar, Odisha was conducted between December 2012 to March 2013 and
      prevalence rate was studied on the basis of age, breed, and sex. MATERIALS AND
      METHODS: A total of 71 fecal samples from suspected diarrheic dogs were collected
      in sterile phosphate buffer saline (10% W/V) and examined by polymerase chain
      reaction (PCR) for detection of canine parvo virus infection, followed by
      epidemiological study in relation to age, breed, and sex. RESULTS: Of 71 samples
      analyzed, 29 (40.85%) were found to be positive by PCR assay. The infection was
      higher in Deshi/local breeds (34.48%), followed by German shepherd (17.24%),
      equal incidences in mixed and Labrador retriever (10.34%), Rottweiler and German
      spitz showed 6.90% each and finally lower incidences in four breeds (3.45%) such
      as Dalmatians, Nea politan mastiff, Pug and Great Dane. Age-wise prevalence study
      revealed the infection being more in the age group of 3-6 months (41.37%),
      followed by equal incidences of 27.59% in 1-3 months and 6-12 months age group,
      and a low incidence in age groups above 12 months (3.45%). The incidence was
      predominantly higher in males (86.21%) than females (13.79%). CONCLUSIONS: The
      epidemiological analysis revealed that the breed wise prevalence was found to be
      more in Deshi breeds as compared to others, age groups below 6 months were found
      to be more prone to parvovirus infection and males were mostly infected.

PMID- 27046993
TI  - Dynamics of faecal egg count in natural infection of Haemonchus spp. in Indian
      goats.
AB  - AIM: Dynamics of faecal egg count (FEC) in Haemonchus spp. infected goats of two
      Indian goat breeds, Jamunapari and Sirohi, in natural conditions was studied and
      effects of genetic and non-genetic factors were determined. MATERIALS AND
      METHODS: A total of 1399 faecal samples of goats of Jamunapari and Sirohi breeds,
      maintained at CIRG, Makhdoom, Mathura, India and naturally infected with
      Haemonchus spp., were processed and FEC was performed. Raw data generated on FEC
      were transformed by loge (FEC+100) and transformed data (least squares mean of
      FEC [LFEC]) were analyzed using a mixed model least squares analysis for fitting
      constant. Fixed effects such as breed, physiological status, season and year of
      sampling and breed * physiological states interaction were used. RESULT: The
      incidence of Haemomchus spp. infection in Jamunapari and Sirohi does was 63.01
      and 47.06%, respectively. The mean LFEC of both Jamunapari and Sirohi (does) at
      different physiological stages, namely dry, early pregnant, late pregnant early
      lactating and late lactating stages were compared. Breed, season and year of
      sampling had a significant effect on FEC in Haemomchus spp. infection. Effect of
      breed * physiological interaction was also significant. The late pregnant does of
      both breeds had higher FEC when compared to does in other stages. CONCLUSION:
      Breed difference in FEC was more pronounced at the time of post kidding (early
      lactation) when sharp change in FEC was observed.

PMID- 27046994
TI  - Plasma mineral profiles and hormonal activities of normal cycling and repeat
      breeding crossbred cows: A comparative study.
AB  - AIM: The present study was carried out to compare the associated role of micro
      minerals and hormones in repeat breeding animals with the normal crossbred cows.
      MATERIALS AND METHODS: Blood samples were collected from 10 normal cycling and 10
      repeat breeding crossbred cows of Ramakrishna Mission Ashram, Narendrapur to
      study the plasma mineral profile and hormonal activities. RESULTS: Zn was found
      to be highly significant (p<0.01) between the two groups. Follicle stimulating
      hormone (FSH) and progesterone showed significant (p<0.05) difference in repeat
      breeding animal from the normal cyclic animal, whereas no significant differences
      were observed in Ca, P, Cu, Se, Co, luteinizing hormone and estradiol level.
      CONCLUSION: It may conclude that repeat breeding condition of crossbred cows in
      farm condition is mainly due to the low level of progesterone, FSH and zinc.

PMID- 27046995
TI  - Heat shock proteins: a therapeutic target worth to consider.
AB  - Heat shock proteins (HSPs) are the molecular chaperones, that are not only
      expressed during the normal growth process of cell cycle consecutively, but also
      get induced in cells during various stress conditions produced by cellular
      insult, environmental changes, temperature, infections, tumors etc. According to
      their molecular weight and functions, HSPs are divided into five major families.
      HSP90, HSP70, HSP60 and HSP100 are the most studied members of the family.
      Experimental studies have proved that overexpression and/or inhibition of HSPs
      play an important role in maintaining the tolerance and cell viability under
      above-described stress conditions. HSP90 is found to be a promising the candidate
      for the diagnosis, prognosis and treatment of cancer. Similarly, HSP70, HSP60 and
      small HSPs experimentally and clinically have potential for the treatment of
      neurodegenerative disease, ischemia, cell death, autoimmunity, graft rejection,
      etc. In a way, exploring, the cytoprotective and immunoregulatory role of HSPs
      can open a new avenue for the drug discovery and treatment of critical diseases. 

PMID- 27046996
TI  - Isolation of Canine parvovirus with a view to identify the prevalent serotype on
      the basis of partial sequence analysis.
AB  - AIM: The aim of this study was to isolate Canine parvovirus (CPV) from suspected
      dogs on madin darby canine kidney (MDCK) cell line and its confirmation by
      polymerase chain reaction (PCR) and nested PCR (NPCR). Further, VP2 gene of the
      CPV isolates was amplified and sequenced to determine prevailing antigenic type.
      MATERIALS AND METHODS: A total of 60 rectal swabs were collected from dogs
      showing signs of gastroenteritis, processed and subjected to isolation in MDCK
      cell line. The samples showing cytopathic effects (CPE) were confirmed by PCR and
      NPCR. These samples were subjected to PCR for amplification of VP2 gene of CPV,
      sequenced and analyzed to study the prevailing antigenic types of CPV. RESULTS:
      Out of the 60 samples subjected to isolation in MDCK cell line five samples
      showed CPE in the form of rounding of cells, clumping of cells and finally
      detachment of the cells. When these samples and the two commercially available
      vaccines were subjected to PCR for amplification of VP2 gene, a 1710 bp product
      was amplified. The sequence analysis revealed that the vaccines belonged to the
      CPV-2 type and the samples were of CPV-2b type. CONCLUSION: It can be concluded
      from the present study that out of a total of 60 samples 5 samples exhibited CPE
      as observed in MDCK cell line. Sequence analysis of the VP2 gene among the
      samples and vaccine strains revealed that samples belonged to CPV-2b type and
      vaccines belonging to CPV-2.

PMID- 27046997
TI  - In vitro antibacterial effect of Withania somnifera root extract on Escherichia
      coli.
AB  - AIM: The aim was to investigate antibacterial activity of Withania somnifera
      (Ashwagandha), an Indian traditional medicinal plant against Escherichia coli
      O78, a pathogenic strain. MATERIALS AND METHODS: Two-fold serial dilutions of 20%
      aqueous W. somnifera root (WSR) extract were inoculated with E. coli O78 @
      1*10(7) colony forming units grown in nutrient broth. Following inoculation,
      turbidity optical density was measured by spectrophotometer at 600 nm in all the
      tubes at 0, 2, 4, 6 and 8 h of incubation at 37 degrees C. RESULT: The results
      revealed that the maximum inhibition of bacterial growth was observed at 1:8
      dilution of WSR extract. The highest dilution of the extract that showed
      inhibited growth of the test organism when compared with control was 1:16.
      Therefore, the minimum inhibitory concentration of aqueous extract of WSR is
      1:16. CONCLUSION: It is concluded that WSR possessed good antibacterial activity,
      confirming the great potential of bioactive compounds and its rationalizing use
      in health care.

PMID- 27046998
TI  - Japanese encephalitis: Challenges and intervention opportunities in Nepal.
AB  - Japanese encephalitis (JE) is a mosquito borne zoonotic disease caused by JE
      virus (JEV). JE has been endemic in Terai region, the lowland plains of Nepal
      bordering India, since 1978. However, in recent years cases of JE has been
      continuously reported from high altitude zones of hills and mountains. Irrigated
      rice farming system, expanded pig husbandry practices, inadequate vaccine
      coverage, low level of public awareness and climate change favoring mosquito
      breeding in higher altitudes might be the probable risk factors for emergence and
      re-emergence of JE in Nepal. Repeated outbreak in endemic areas and geographical
      expansion to newer areas have created huge challenge for JE prevention and
      control. At present, JE is one of the major public health concern of Nepal.
      Expanding vaccine coverage, improving agricultural practices, generating public
      awareness, supporting for use of mosquito avoiding practices and regional
      collaboration at border against JE can be helpful in getting better control over
      it in future. 

PMID- 27046999
TI  - Evaluation of pesticide residues in human blood samples from Punjab (India).
AB  - AIM: The present study was undertaken to estimate the current status of residues
      of organochlorine pesticides (OCPs), organophosphates (OPs) and synthetic
      pyrethroids (SPs) pesticides in human blood. MATERIALS AND METHODS: Human blood
      samples were analyzed by gas chromatography and confirmed by gas chromatography
      mass spectrometry in selective ion monitoring mode. RESULTS: The gas
      chromatographic analysis of human blood samples collected from Punjab revealed
      the presence of p,p'-dichlorodiphenyl dichloroethylene (DDE), p,p'
      dichlorodiphenyl dichloroethane (DDD), o,p' DDE and beta-endosulfan at mean
      levels of 15.26, 2.71, 5.62 and 4.02 ng/ml, respectively. p,p' DDE residue was
      observed in 18.0% blood samples, and it contributes 55% of the total pesticide
      burden in human blood. The difference of total dichlorordiphenyl trichloroethane
      (DDT) between different age groups of humans was found to be statistically
      significant (p<0.05). The difference of DDT and endosulfan between dietary
      habits, gender and spraying of pesticides was found statistically non
      significant, however endosulfan residues were observed only in pesticide
      sprayer's population. CONCLUSION: Occurrence of p,p' DDE, p,p' DDD, o,p' DDE in
      human blood indicated restricted use of DDT. However, presence of endosulfan
      residues in occupationally exposed population is a matter of public health
      concern.

PMID- 27047000
TI  - Seroprevalence studies on animal chlamydiosis amongst ruminants in five states of
      India.
AB  - BACKGROUND AND AIM: Animal chlamydiosis, caused by different chlamydial species,
      is characterized by clinical or subclinical disease manifestations in cattle,
      buffalo, ovine, caprine and wild animal species. Animal chlamydiosis often
      remains underdiagnosed or undiagnosed, and its status in many parts of India is
      still unknown. Hence, the present study was conducted to determine the
      seroprevalence of animal chlamydiosis amongst ruminant livestock species of five
      states of India. MATERIALS AND METHODS: Totally, 2127 randomly selected serum
      samples collected from ruminant livestock species viz. cattle (n=430), buffaloes
      (n=429), sheep (906) and goats (n=362), were tested by agar gel precipitation
      test for chlamydiosis between 2002 and 2011. Precipitating antigen was prepared
      from locally isolated strain of Chlamydia psittaci after treatment with sodium
      deoxycholate. RESULTS: The chlamydial seroprevalence detected amongst ruminants
      in five states of India was: Himachal Pradesh: Cattle-10.90%, sheep-10.60% and
      goats- 22.46%; Punjab: Cattle-1.45%; Andhra Pradesh: Cattle-2.80%, buffaloes
      0.93%, sheep-8.90% and goats-9.46%; Maharashtra: goats-8.33%; Jammu and Kashmir:
      sheep-12.50%. The mean seroprevalence values of each animal species are: Cattle
      4.65%, buffaloes-0.93%, sheep-9.82% and goats-19.33%. CONCLUSION: The results
      indicate the endemic nature of animal chlamydiosis across five states in India.
      Hence, it requires further extensive studies in other parts of India also using
      chlamydial species-specific diagnostics to ascertain overall countrywide
      prevalence of the disease. The zoonotic nature of the chlamydiae of ruminant
      origin further adds significance to such prevalence studies.

PMID- 27047001
TI  - Pathology and molecular diagnosis of classical swine fever in Mizoram.
AB  - AIM: Clinical histopathological and molecular diagnosis of classical swine fever
      disease in pigs of Mizoram. MATERIALS AND METHODS: Totally, 31 clinically
      suspected pigs from 6 districts of Mizoram were examined, and clinical symptoms
      were recorded. Detailed post mortem examination of all the 31 dead animals was
      conducted, and gross changes were recorded. Tissue samples were collected for
      histopathological examination and molecular diagnosis. The collected tissues
      (tonsil, lymph nodes, spleen) were also processed for RNA extraction. Reverse
      transcription polymerase chain reaction (RT-PCR) was performed to detect the
      specific gene fragments of classical swine fever virus (CSFV). RESULTS: Clinical
      examination of all the 31 suspected pigs revealed typical clinical signs of CSF.
      All the animals also showed typical gross and microscopic lesions of CSF. RT-PCR
      on tissue samples amplified the 421bp, 449bp and 735bp region of 5'NCR, non
      structural protein 5B and E(rns) gene regions of CSFV, respectively. Nested PCR
      for internal region of E2 gene also amplified the expected product of 271bp using
      PCR product of whole E2 region as template DNA. CONCLUSION: CSF is highly endemic
      disease in Mizoram. The viral strains circulating in this region are highly
      virulent. The disease can be diagnosed specifically using RT-PCR.

PMID- 27047002
TI  - Chemical composition of solar dried blood and the ruminal content and its effect
      on performance of Japanese quails.
AB  - AIM: The aim was to determine the chemical composition of solar dried blood and
      rumen content (DBRC) and further ascertain the concentration at which DBRC could
      be included in Japanese quail diets without any adverse effect on its
      performance. MATERIALS AND METHODS: Feeding trial on the effect of DBRC on
      performance of Japanese quails was studied up to 5 weeks. 252 numbers of day old
      (Nandanam Type III breed) Japanese quails were purchased from Poultry Research
      Station, Madhavaram and divided into 7 batches (control+ six treatments) each
      consisting of 36 birds. The DBRC was included at 0%, 5%, 10%, 15%, 20%, 25% and
      30% in diets as control, treatment-1 (T1), treatment-2 (T2), treatment-3 (T3),
      treatment-4 (T4), treatment-5 (T5) and treatment-6 (T6) respectively in a
      completely randomized design to replace soybean meal in Japanese quail feed. The
      birds were provided with ad-labidum feed and drinking water ad-libitum during the
      entire experimental period. RESULTS: The crude protein (CP), crude fiber (CF),
      ether extract (EE) and ash contents of DBRC were 35.87%, 17.40%, 3.6% and 12.6%,
      respectively. The amount of essential amino acids and non-essential amino acid
      content were found to be 12.98 and 4.87 (g/100 g of feed) respectively in DBRC
      feed. Result showed that all birds fed DBRC diets performed better than the
      control group. Mortality was unaffected by dietary treatments. There was a
      significant difference (p<0.01) observed in weight gain in treatment groups
      compared to the control. CONCLUSION: Up to 30% DBRC could be incorporated in the
      diets of Japanese quails without any adverse effects on its performance.

PMID- 27047003
TI  - Associations of farm management practices with annual milk sales on smallholder
      dairy farms in Kenya.
AB  - AIM: Cows on smallholder dairy farms (SDF) in developing countries such as Kenya
      typically produce volumes of milk that are well below their genetic potential. An
      epidemiological study was conducted to determine reasons for this low milk
      production, including limited use of best management practices, such as
      suboptimal nutritional management. METHODS: An observational cross-sectional
      study of 111 SDF was performed in Nyeri County, Kenya in June of 2013 determining
      the effect of cow factors, farmer demographics and farm management practices on
      the volume of milk sold per cow per year (kg milk sold/cow). In particular, the
      effect of feeding high protein fodder trees and other nutritional management
      practices were examined. RESULTS: Approximatly 38% of farmers fed fodder trees,
      but such feeding was not associated with volume of milk sold per cow, likely due
      to the low number of fodder trees per farm. Volume of milk sold per cow was
      positively associated with feeding dairy meal during the month prior to calving,
      feeding purchased hay during the past year, deworming cows every 4 or more months
      (as opposed to more regularly), and having dairy farming as the main source of
      family income. Volume of milk sold per cow was negatively associated with a
      household size of >5 people and feeding Napier grass at >2 meters in height
      during the dry season. An interaction between gender of the principal farmer and
      feed shortages was noted; volume of milk sold per cow was lower when female
      farmers experienced feed shortages whereas milk sold per cow was unaffected when
      male farmers experienced feed shortages. CONCLUSIONS: These demographic and
      management risk factors should be considered by smallholder dairy farmers and
      their advisors when developing strategies to improve income from milk sales and
      animal-source food availability for the farming families.

PMID- 27047004
TI  - Microbial quality, instrumental texture, and color profile evaluation of edible
      by-products obtained from Barbari goats.
AB  - AIM: The study was conducted to estimate the contribution of edible byproducts of
      Barbari kids to their live and carcass weight as well as to assess textural and
      color characteristics and microbiological status of these byproducts. MATERIALS
      AND METHODS: Percent live weight, Percent carcass weight, Texture, color, and
      microbiological analysis was done for edible byproducts viz. liver, heart,
      kidney, spleen, brain and testicle and longissimus dorsi muscle was taken as a
      reference. RESULTS: The edible byproducts of Barbari kids constitute about 3% of
      the live weight of an animal of which liver contributed maximum (1.47%) followed
      by testicles (0.69%) and heart (0.41%). While the same constituted 3.57, 1.70,
      and 0.99%, respectively on carcass weight. There was significant (p<0.05)
      difference among all organs regarding textural properties. Liver required the
      maximum shear force and work of shear (121.48N and 32.19 kg-sec) followed by
      spleen and heart. All organs revealed characteristics color values (L*, a*, b*,
      chroma, and hue) which were significantly different (p<0.05) from muscle values.
      The total viable count, coliform count showed slight differences for all organs
      studied. The staphylococcus counts were low with little differences among organs.
      CONCLUSION: Edible byproducts have a significant contribution to carcass weight
      which could enhance total edible portion of the carcass. Efficient utilization of
      these by-products returns good source of revenue to the meat industries. Textural
      and color analysis give information for their incorporation in comminuted meat
      products, and microbial study tells about the storage study. However, study was
      in the preliminary and basic step forward toward better utilization of 3% of live
      animal which could increase the saleable cost of animal by 6.94%.

PMID- 27047005
TI  - Detection of Avibacterium paragallinarum by Polymerase chain reaction from
      outbreaks of Infectious coryza of poultry in Andhra Pradesh.
AB  - AIM: This study was carried out for the detection of Avibacterium paragallinarum
      from outbreaks of infectious coryza of poultry. MATERIALS AND METHODS: The
      polymerase chain reaction (PCR) was standardized for the diagnosis of infectious
      coryza by using infectious coryza Killed vaccine, ventri biologicals, Pune as
      source of DNA of A. paragallinarum. Five outbreaks of infectious coryza from
      Andhra Pradesh were investigated in the present study. A total of 56 infra
      orbital sinus swabs and 22 nasal swabs were tested by PCR. RESULTS: PCR analysis
      showed 56 positives (71.7%) for infectious coryza out of total 78 samples tested.
      Of 56 infra orbital sinus swabs tested, 47 were positive (83.9%) and 9 nasal
      swabs (40.9%) out of 22 tested had given positive results for infectious coryza.
      Samples collected from birds at acute stage of disease and samples collected
      before treatment with antibiotics were given better results on PCR. CONCLUSION:
      For preventing the economic losses associated with the disease, an early,
      accurate and rapid diagnosis is essential. PCR is a rapid and highly sensitive
      diagnostic technique which can substitute conventional cultural examination.

PMID- 27047006
TI  - In vitro utilization of lime treated olive cake as a component of complete feed
      for small ruminants.
AB  - AIM: The current in vitro study was carried out to determine the chemical
      composition and inclusion level of lime treated olive cake on acid detergent
      fiber (ADF) replacement basis in adult male goats. MATERIALS AND METHODS: Crude
      olive cake was collected and evaluated for proximate composition and protein
      fractionation. It was treated with 6% lime and incubated for 1 week under room
      temperature in 2 kg sealed polythene bags and was evaluated for proximate
      composition after incubation. Different isonitrogenous complete diets containing
      0-50% of lime treated olive cake on ADF replacement basis were formulated as per
      the requirement of adult male goats. In ADF replacement, fiber and concentrate
      sources were replaced by lime treated olive cake by replacing the 0-50% ADF
      percentage of the total 40% ADF value of complete feed. The formulated complete
      diets were tested for in vitro degradation parameters. RESULTS: Treatment of
      olive cake with 6% slaked lime increased availability of cellulose and alleviated
      digestibility depression caused by high ether extract percentage. Organic matter,
      nitrogen free extract, ADF and neutral detergent fiber were significantly lowered
      by lime treatment of olive cake. The cornell net carbohydrate and protein system
      analysis showed that non-degradable protein represented by acid detergent
      insoluble nitrogen (ADIN) was 21.71% whereas the non-available protein
      represented by neutral detergent insoluble nitrogen (NDIN) was 38.86% in crude
      olive cake. The in vitro dry matter degradation (IVDMD) values were comparable at
      all replacement levels. However, a point of inflection was observed at 40% ADF
      replacement level, which was supported by truly degradable organic matter (TDOM),
      microbial biomass production (MBP), efficiency of MBP and partitioning factor
      values (PF). CONCLUSION: In our study, we concluded that there is comparable
      difference in composition of Indian olive cake when compared with European olive
      cake. The most important finding was that about 78% of nitrogen present in Indian
      olive cake is available to animal in contrary to that of European olive cake. We
      concluded from in vitro studies that Indian olive cake can be included in
      complete feed at 30% level (w/w; 40% ADF replacement) for feeding in small
      ruminants without compromising in vitro degradability of the feed.

PMID- 27047007
TI  - Clinico-pathology, diagnosis and management of Cysticercus fasciolaris and
      Hymenolepis diminuta co-infection in wistar rats.
AB  - AIM: The present study was undertaken to study the pathology and control of
      sudden unexplained mortality in wistar rats. MATERIALS AND METHODS: This study
      was conducted in a colony of 25 male wistar rats where there was mortality of
      nine rats. The dead rats were subjected to thorough post-mortem examination and
      necropsy samples were processed for hematoxylin and eosin staining for
      histopathological studies. Faecal samples of live rats were studied for the
      presence of parasitic eggs. Treatment with anthelmintics was given to manage the
      mortality and infections. RESULTS: The investigation revealed a natural co
      infection of Cysticercus fasciolaris and Hymenolepis diminuta in wistar rats,
      which were pathogenic enough to cause mortality. Typical lesions associated with
      the parasites were found in the dead rats. The mortality and infection were
      managed with common anthelmintics. CONCLUSION: C. fasciolaris and H. diminuta
      infection can cause mortality in wistar rats even when individually they cause
      asymptomatic infection. The mortality and infection can be managed with common
      anthelmintics.

PMID- 27047008
TI  - Virulence genes detection of Salmonella serovars isolated from pork and
      slaughterhouse environment in Ahmedabad, Gujarat.
AB  - AIM: The aim was to detect virulence gene associated with the Salmonella serovars
      isolated from pork and Slaughterhouse environment. MATERIALS AND METHODS:
      Salmonella isolates (n=37) used in this study were isolated from 270 pork and
      slaughter house environmental samples collected from the Ahmedabad Municipal
      Corporation Slaughter House, Ahmedabad, Gujarat, India. Salmonella serovars were
      isolated and identified as per BAM USFDA method and serotyped at National
      Salmonella and Escherichia Centre, Central Research Institute, Kasauli (Himachal
      Pradesh, India). Polymerase chain reaction technique was used for detection of
      five genes, namely invA, spvR, spvC, fimA and stn among different serovars of
      Salmonella. RESULTS: Out of a total of 270 samples, 37 (13.70%) Salmonella were
      isolated with two serovars, namely Enteritidis and Typhimurium. All Salmonella
      serovars produced 284 bp invA gene, 84 bp fimA and 260 bp amplicon for
      enterotoxin (stn) gene whereas 30 isolates possessed 310 bp spvR gene, but no
      isolate possessed spvC gene. CONCLUSION: Presence of invA, fimA and stn gene in
      all isolates shows that they are the specific targets for Salmonella
      identification and are capable of producing gastroenteric illness to humans,
      whereas 20 Typhimurium serovars and 10 Enteritidis serovars can able to produce
      systemic infection.

PMID- 27047009
TI  - Morphological and histological identification of Paramphistomum cervi (Trematoda:
      Paramiphistoma) in the rumen of infected sheep.
AB  - AIM: This study was undertaken to identify Paramphistomum cervi on the basis of
      its morphology and histology to be the common cause of paramphistomosis in
      infected sheep and its differentiation from other similar Paramphistomes in
      Gujarat. MATERIALS AND METHODS: Adult rumen flukes were recovered from the rumen
      of naturally infected sheep slaughtered in various abattoirs in Gujarat. Some
      adult flukes were flattened and stained in Borax carmine, and some were sectioned
      in the median sagittal plane and histological slides of the flukes were prepared
      for detailed morphological and histological studies. RESULT: Microscopic pictures
      of the parasite used in identification define the similarity in the morphology
      and histology of the anterior sucker, pharynx, esophagus, genital atrium,
      posterior sucker (acetabulum) and testes to the P. cervi. CONCLUSION: It can be
      concluded that the most common species found in sheep infected with
      Paramphistomosis is P. cervi on the basis of its histo-morphological appearance
      in Gujarat.

PMID- 27047010
TI  - The influence of altitude and landforms on some biochemical and hematological
      parameters in Ouled Djellal ewes from arid area of South East Algeria.
AB  - AIM: This study was conducted on Ouled Djellal ewes in arid area of south-east
      Algeria in order to reveal the influence of altitude and landforms on some
      hematological and biochemical parameters. MATERIALS AND METHODS: A total of 160
      ewes having 3-5 years of age, multiparous, non-pregnant, non-lactating and reared
      in arid areas of South East Algeria were included. Blood samples were divided
      according to factors of altitude and landform (plain region at 150 m above sea
      level, tableland region at 600 m above sea level and mountain region at 1000 m
      above sea level). The whole blood was analyzed for hematology, and plasma samples
      for biochemical analysis. RESULTS: The study found lowest glucose concentrations
      were detected in tableland region at 600 m. In plain region at 150 m, ewes had a
      higher (p<0.01) concentration of cholesterol and triglyceride. Furthermore, a
      higher concentration of total proteins (p<0.01) and urea (p<0.05) were detected
      in plain region at 150 m. The average blood creatinine concentration in mountain
      ewes at 1000 m and tableland ewes at 600 m were higher (p<0.05) that in plain
      ewes at 150 m. The highest calcium concentration was found at the altitude of 150
      m and the lowest at the altitude of 1000 m (1.12+/-0.35 mmol/L vs. 0.52+/-0.03
      mmol/L). Phosphorus levels were higher at altitudes of 150 m than at the altitude
      of 600 m and 1000 m (0.93+/-0.42 mmol/L vs. 0.68+/-0.54 mmol/L, 0.23+/-0.01
      mmol/L). The highest hemoglobin concentration and value of hematocrit were
      detected in mountain ewes at the altitude of 1000 m (120.61 g/L, 40%) and the
      lowest at the altitude of 150 m (73.2 g/L, 31%) (p<0.001). CONCLUSION: We
      concluded that hematological and biochemical parameters in Ouled Djellel ewes
      reared in arid area may be affected by altitude and landforms.

PMID- 27047011
TI  - Relation between antioxidant status and postpartum anestrous condition in Murrah
      buffalo.
AB  - AIM: Objective of the present study was to investigate the relation between
      antioxidant status and postpartum anestrous (PPA) condition in Murrah buffalo.
      MATERIALS AND METHODS: Jugular blood samples were collected from two different
      groups of Murrah buffaloes each group consisting of 20 animals. Group I was of
      PPA and Group II were of cyclic buffaloes. The animals selected were examined for
      confirmation for cyclic and acyclic condition (>120 days) after calving by
      routine transrectal ultrasonography. Heard record was also used for cross
      confirmation. RESULTS: The analysis of antioxidants in plasma and hemolysates
      revealed that the levels of vitamin E, beta-carotene and reduced glutathione in
      plasma and superoxide dismutase (SOD) in hemolysate were significantly higher in
      cyclic animals than PPA animals. The levels of vitamin C, SOD and glutathione
      peroxidase in plasma did not show any significant difference among the two groups
      studied. The low antioxidant level in affected animals may predispose them toward
      PPA condition. CONCLUSION: Stress imposed by pregnancy and lactation affected the
      reproductive performance in PPA animals which might be inherently more
      susceptible to these stressors than those who were normal cyclic as all the
      animals were maintained under similar feeding and management practices.

PMID- 27047012
TI  - Tick fauna of Malaysian red jungle fowl (Gallus gallus) in Bangi, Malaysia.
AB  - AIM: The red jungle fowl is generally considered as one of the endangered Asian
      wild Galleopheasants due to man-made encroachment of their habitats, coupled with
      the effect of disease and disease causing organisms like ticks and tick-borne
      infections. This study aimed to determine the tick fauna of the red jungle fowl
      and their predilection sites based on developmental stages. MATERIALS AND
      METHODS: A total of 33 jungle fowls were sampled for this study from Bangi area
      of Selangor State, Peninsular Malaysian. The birds were captured using a locally
      made trap made-up of loops and bites. Ticks present on their bodies were detached
      using fine forceps and identified morphologically under a dissecting microscope.
      RESULTS: 91% of the jungle fowls were infested with ticks, all of which belongs
      to the species Haemaphysalis wellingtoni. The ear region appeared to be the most
      common predilection site (63%) for all the developmental stages in which the
      larval stages are solely restricted to that region. Nymphal and adult stages were
      distributed on the comb, wattle, and facial region in addition to the ear region.
      CONCLUSION: This study was the first in its kind and showed a high prevalence of
      tick infestation among jungle fowls. H. wellingtoni was known to be a vector in
      transmission of many tick-borne pathogens. Therefore, there is the need for
      further investigation to identify the various pathogens associated with this
      tick.

PMID- 27047013
TI  - Effect of incorporation of walnut cake (Juglans regia) in concentrate mixture on
      degradation of dry matter, organic matter and production of microbial biomass in
      vitro in goat.
AB  - AIM: This study was carried out to investigate the effect of incorporation of
      different level of walnut cake in concentrate mixture on in vitro dry matter
      degradation in order to determine its level of supplementation in ruminant
      ration. MATERIALS AND METHODS: Walnut cake was used @ 0, 10, 15, 20, 25 and 30%
      level to formulate an iso-nitrogenous concentrate mixtures and designated as T1,
      T2, T3, T4, T5 and T6 respectively. The different formulae of concentrate
      mixtures were used for in vitro gas production studies using goat rumen liquor
      with wheat straw in 40:60 ratio. Proximate composition, fiber fractionation and
      calcium and phosphrous content of walnut cake were estimated. RESULT: The per
      cent IVDMD value of T1 and T2 diets was 68.42 +/- 1.20 and 67.25 +/- 1.37
      respectively which was found highest (P<0.05) T3, T4, T5 and T6. Similar trend
      was also found for TDOM and MBP. Inclusion of walnut cake at 10% level in the
      concentrate mixture does not affect in vitro dry matter digestibility (IVDMD),
      truly degradable organic matter (TDOM, mg/200 mg DM), total gas production,
      microbial biomass production (MBP) and efficiency of microbial biomass production
      (EMP). CONCLUSION: It is concluded that walnut cake incorporation up to 10% level
      in the iso -nitrogenous concentrate mixture has no any negative effect on in
      vitro digestibility of dry matter (DM), TDOM, MBP, EMP and total gas production
      in goat.

PMID- 27047014
TI  - Hemato-biochemical and pathological changes on avian influenza in naturally
      infected domestic ducks in Egypt.
AB  - AIM: Few studies have been made in regard to avian influenza (AI) in ducks, thus
      the aim of this work was planned to investigate the hematological, biochemical,
      and pathological changes in domestic Egyptian ducks naturally infected with AI.
      MATERIALS AND METHODS: 30 duck from private backyards 3-month-old 15 were
      clinically healthy (Group 1) and the other fifteen (Group 2) were naturally
      diseased with AI (H5N1). The disease was diagnosed by polymerase chain reaction
      as H5N1. RESULTS: Duck showed cyanosis, subcutaneous edema of head and neck with
      nervous signs (torticollis). Hematological studies revealed a microcytic
      hypochromic anemia. Biochemical studies revealed a significant decrease in total
      protein, albumin and globulin concentration with significant increase of
      activities of aspartate aminotransferase, alanine aminotransferase, alkaline
      phosphatase, Upsilon-glutamyl transpeptidase, lactic acid dehydrogenase and
      creatine phsphokinase. Prominent increase in creatinine and uric acid in addition
      to hypocalcemia and hyperphosphatemia were significantly detected in the infected
      ducks. Histopathological finding confirm these investigations. CONCLUSION: The
      highly pathogenic AIV (A/H5N1) became more severe infectious to ducks than before
      and causes nervous manifestations and blindness which were uncommon in ducks.
      Besides the significant increases of hepatic enzymes, brain, heart, and renal
      markers as a response to virus damage to these organs.

PMID- 27047015
TI  - Genotyping of major histocompatibility complex Class II DRB gene in Rohilkhandi
      goats by polymerase chain reaction-restriction fragment length polymorphism and
      DNA sequencing.
AB  - AIM: To study the major histocompatibility complex (MHC) Class II DRB1 gene
      polymorphism in Rohilkhandi goat using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and nucleotide sequencing techniques.
      MATERIALS AND METHODS: DNA was isolated from 127 Rohilkhandi goats maintained at
      sheep and goat farm, Indian Veterinary Research Institute, Izatnagar, Bareilly. A
      284 bp fragment of exon 2 of DRB1 gene was amplified and digested using BsaI and
      TaqI restriction enzymes. Population genetic parameters were calculated using
      Popgene v 1.32 and SAS 9.0. The genotypes were then sequenced using Sanger
      dideoxy chain termination method and were compared with related breeds/species
      using MEGA 6.0 and Megalign (DNASTAR) software. RESULTS: TaqI locus showed three
      and BsaI locus showed two genotypes. Both the loci were found to be in Hardy
      Weinberg equilibrium (HWE), however, population genetic parameters suggest that
      heterozygosity is still maintained in the population at both loci. Percent
      diversity and divergence matrix, as well as phylogenetic analysis revealed that
      the MHC Class II DRB1 gene of Rohilkhandi goats was found to be in close cluster
      with Garole and Scottish blackface sheep breeds as compared to other goat breeds
      included in the sequence comparison. CONCLUSION: The PCR-RFLP patterns showed
      population to be in HWE and absence of one genotype at one locus (BsaI), both the
      loci showed excess of one or the other homozygote genotype, however, effective
      number of alleles showed that allelic diversity is present in the population.
      Sequence comparison of DRB1 gene of Rohilkhandi goat with other sheep and goat
      breed assigned Rohilkhandi goat in divergence with Jamanupari and Angora goats.

PMID- 27047016
TI  - Comparative study on the immunopotentiator effect of ISA 201, ISA 61, ISA 50, ISA
      206 used in trivalent foot and mouth disease vaccine.
AB  - AIM: A comparison study was conducted to explore the best internationally
      available adjuvant that could be used in production of a highly potent foot and
      mouth disease (FMD) vaccine, that could stimulate a strong immune response and
      possibly give greater protection against FMD. MATERIALS AND METHODS: Four
      experimental batches of trivalent FMD vaccine were prepared with different
      available oil adjuvants which included Montanide ISA 201, 206, 61 and 50.
      RESULTS: The results indicated that vaccines emulsified using Montanide ISA 201
      and Montanide ISA 206 adjuvants elicited a protective humoral immune response
      from the 2(nd) week postvaccination (WPV) as for ISA 201 with serum
      neutralization test (SNT) and enzyme-linked immune sorbent assay (ELISA) antibody
      titers of 1.62+/-0.047(a) and 1.8+/-0.049(a), 1.59+/-0.076(a) and 1.836+/
      0.077(a), and 1.71+/-0.06(b) and 1.96+/-0.074(b) for serotypes O, A, SAT2,
      respectively, and for ISA 206 at SNT and ELISA antibody titers of 1.5+/-0.082(a)
      and 1.84+/-0.084(a), 1.56+/-0.037(a) and 1.818+/-0.052(a), and 1.5+/-0.106(a,b)
      and 1.81+/-0.104(a,b) for FMD virus serotypes O, A and SAT2, respectively. For
      ISA 61 and ISA 50, the protective antibody titer appeared in the 3(rd) WPV. In
      the ISA 61 FMD vaccine, SNT and ELISA titer were 1.59+/-0.076(a) and 1.9+/
      0.094(a), 1.53+/-0.056(a) and 1.83+/-0.070(a), and 1.5+/-0.082(a) and 1.84+/
      0.094(a) for serotypes O, A and SAT2, respectively, and in the case of ISA 50 FMD
      vaccine, the SNT, and ELISA titer were recorded for serotypes O, A and SAT2
      respectively, 1.59+/-0.037(a) and 1.8+/-0.030(a), 1.68+/-0.056(a,b) and 1.916+/
      0.065(a,b), and 1.65+/-0.082(a) and 1.9+/-0.09(a). On estimating the cellular
      immune response, the highest delta optical density levels for ISA 201 (0.395
      0.460) and ISA 206 (0.375-0.428) were observed on 14 and 21 days post vaccination
      (DPV) respectively, while the highest levels of lymphoproliferation for ISA 61
      (0.375-0.455) and ISA 50 (0.411-0.430) were on 21 and 28 DPV, respectively.
      CONCLUSION: The duration of immunity from Montanide ISA oils (201, 206, 61 and
      50) FMD vaccines is a long-lived immunity which ranged between 32 and 38 weeks
      post vaccination but the Montanide ISA 201 FMD vaccine is superior to the others
      in the rapid cellular immune response of the vaccinated animals which showed its
      highest level within 14 days post vaccination.

PMID- 27047017
TI  - Prevalence of gastrointestinal helminth infections in ovine population of Kashmir
      Valley.
AB  - AIM: Gastrointestinal (GI) helminth parasitism is one of the major constraints
      for profitable sheep production. Due to variations in the prevalence of GI
      helminths from region to region, it becomes important to map out accurately the
      parasitic fauna of a particular region for development of suitable control
      measures. MATERIALS AND METHODS: An extensive study of GI helminths was carried
      out in Budgam district of Kashmir Valley over a period of 1 year. A total of 1200
      fresh ovine faecal samples from both sexes of young ones and adults were
      collected in sterilized plastic bags and examined by standard sedimentation and
      floatation techniques. Positive faecal samples (15-20%) in each season were
      examined by Stoll's dilution method to determine the parasitic load. A total of
      120 faecal samples (30 samples in each season) positive for strongyle eggs were
      subjected to coproculture using Petridish method and the third stage larvae were
      harvested to find out prevalence of different genera of strongyle worms. RESULTS:
      The overall prevalence of GI helminths was found to be 77% with platyhelminths
      and nemathelminthes in 26.58 and 60.92% animals, respectively. The overall
      prevalence of mixed GI helminths was found to be 8.67%. Eggs of various helminths
      encountered in the present study were those of Fasciola spp. (3.58%),
      Dicrocoelium spp. (11.58%), paramphistomes (4.83%), Moniezia spp. (7.92%),
      strongyle worms including Nematodirus spp. (57.75%), Strongyloides spp. (1.67%),
      and Trichuris spp. (1.5%). On coprocultural examination Haemonchus spp. (55%) was
      found to be most predominant strongyle worm followed by Trichostrongylus spp.
      (17.5%), Ostertagia spp. (11.67%), Oesophagostomum spp. (9.17%), and Chabertia
      spp. (6.67%). On seasonal basis, highest prevalence of GI helminths was recorded
      in summer (83.00%) followed by spring (78.67%), winter (76.33%), and autumn
      (70.00%), the difference being statistically non-significant (p>0.05). The
      prevalence of platyhelminths (Fasciola spp., Dicrocoelium spp. and Moniezia spp.)
      was found to be non-significantly higher in winter, but paramphistomes showed the
      highest prevalence in the summer season. Nemathelminth infection was found
      highest in summer season and lowest during the winter season. Eggs per gram (EPG)
      ranged from 0 to 1800, and an average EPG count was found to be 454.35+/-27.85.
      EPG was found to be highest in summer (684.00+/-69.83) and lowest in winter
      (202.38+/-18.82). The overall prevalence of GI helminths was found more in adult
      sheep (83.00%) compared to young ones (53.11%), the difference being
      statistically significant (p<0.05). Similarly, the prevalence of helminths was
      found to be higher in females (78.32%) as compared to males (72.97%), the
      variation being statistically non-significant (p>0.05). CONCLUSION: Seasonal
      variation plays an important role in the prevalence of GI helminths in addition
      to age and sex of the animal.

PMID- 27047018
TI  - Prevalence of intestinal and haemoprotozoan parasites of small ruminants in Tamil
      Nadu, India.
AB  - AIM: The aim of the present study is to assess the prevalence of intestinal and
      haemoprotozoan parasites of small ruminants (Sheep and Goats) in North Western
      part of Tamil Nadu, India. MATERIALS AND METHODS: A total of 630 faecal samples
      (251-sheep, 379-goats) and 554 blood smears (242-sheep, 312-goats) were examined,
      for the presence of eggs of intestinal and haemoprotozoan parasites,
      respectively. The samples were received from the Veterinary college hospital and
      Veterinary dispensaries in North Western part of Tamil Nadu. Faecal samples were
      processed by sedimentation technique and examined under low power objective
      (*10), and blood smears were stained using Giemsa's technique and examined under
      oil immersion (*100). RESULT: The analysis of data on the prevalence of
      intestinal and haemoprotozoan parasites of sheep and goats in North Western part
      of Tamil Nadu for the period from 2004 to 2013, showed an overall prevalence of
      intestinal parasites was found to be 67% and 35% in sheep and goats,
      respectively, whereas only 11% of sheep and 3% of goats had the haemoprotozoan
      parasitic infection. Highly, significant difference (p<0.01) in the prevalence of
      intestinal (chi(2)=65), and hemoprotozoan (chi(2)=15.4) parasitism was observed
      between sheep and goats. Intestinal parasites such as strongyles, Trichuris,
      Moniezia, amphistome, and coccidia were identified in which the highest
      prevalence was observed with coccidia, followed by strongyles, Monezia,
      Trichuris, and least with amphistome in both the sheep and goats. The
      haemoprotozoan parasites recorded were Theileria and Anaplasma species, of which,
      Anaplasma spp. being the highest and Theileria spp. the least prevalent in both
      the sheep and goats. The seasonal prevalence of intestinal parasites showed
      highest in rainy season, followed by moderate in winter and least with summer in
      both the sheep and goats, whereas the haemoprotozoan parasites recorded were the
      highest in summer followed by winter and least with rainy season. CONCLUSION: The
      present study suggests that North Western part of Tamil Nadu is highly endemic
      for intestinal parasites such as coccidia and strongyles and haemoprotozoans such
      as Anaplasma and Theileria species in small ruminants.

PMID- 27047019
TI  - Effect of drinking water temperature on physiological variables of crossbred
      dairy cattle at high altitude temperate region of Himalayas.
AB  - AIM: The objective of study was to investigate the effects of drinking water on
      certain physiological parameters such as heart rate (HR), respiration rate (RR),
      rectal temperature (RT) and, ruminal motility (RM). MATERIALS AND METHODS: The
      experiment was carried out on 18 farm bred lactating crossbred cows. The animals
      selected for the study were divided into three groups of six animals each on the
      basis of milk yield and parity and were allotted to three treatment group of six
      each such as ambient drinking water temperature at 10.25+/-0.28 degrees C
      (ambient water, T1), drinking water temperature at 15-20 degrees C (T2) and
      drinking water temperature at 35-40 degrees C (T3). All the managemental
      practices were kept similar during experiment except drinking water temperatures
      physiological variables such as HR, RR, RT, and RM of the individual cow was
      measured and recorded twice in a day at 800 h and again at 1400 h two consecutive
      days in a week 15 min after providing drinking water. RESULT: HR and RR at
      morning and at evening recorded were within the normal physiological level for
      all the treatment groups. However, RT at morning was comparable in all the
      treatments whereas at evening it was significantly (p<0.01) higher for cows
      consuming in T2 and in T3 than cows consumed (T1). The RM during morning among
      the treatments were non-significant as compared to the rumen motility at evening
      was significantly higher for (T1) and (T2) than for cows in (T3). CONCLUSION: It
      can be concluded that offering warm drinking water at 35-40 degrees C to
      crossbred lactating dairy cow is beneficial during winter at high altitude
      temperate region.

PMID- 27047020
TI  - Factors affecting survivability of local Rohilkhand goats under organized farm.
AB  - AIM: To study the pattern of mortality as affected by age, season and various
      diseases in local goats of Rohilkhand region maintained at the Indian Veterinary
      Research Institute, Bareilly. MATERIALS AND METHODS: Post-mortem records of 12
      years (2000-01 to 2011-12) were used, and total 243 mortality data were collected
      and analyzed. The causes of mortality were classified into seven major classes
      viz. digestive disorders, respiratory disorders, cardiovascular disorders,
      musculoskeletal disorder, parasitic disorders, mixed disorders (combination of
      digestive, respiratory, parasitic, and cardiovascular disorders) and
      miscellaneous disorders (cold, hypoglycemia, emaciation, endometritis, traumatic
      injury, etc.). RESULTS: The average mortality was 10.93%. The overall mortality
      was more during rainy season followed by winter and summer season. The mortality
      in 4-6 months of age was high (2.52%) followed by 0-1 month (2.34%) and 2-3
      months (1.35%). The average mortality among adult age groups (>12 months) was
      3.42%. The mortality showed declining trend with the advancement of age up to 3
      months and then again increased in 4-6 months age group. The digestive diseases
      (3.51%) followed by respiratory diseases (1.89%) and parasitic diseases (1.48%)
      contributed major share to the total mortality occurred and the remaining
      disorders were of lesser significance in causing death in goats. There is
      significant (p<0.01; chi(2)=55.62) association between year with season and age
      with the season (p<0.05, chi(2)=16.083) found in the present study. CONCLUSION:
      This study confirms that overall mortality rate averaged 10.93% (ranged between
      1.10% and 25.56%) over 12 years under semi-intensive farm condition. It was
      generally higher in rainy season. The mortality remains higher in kids
      particularly under 1 month of age. The digestive diseases contributed major share
      to overall mortality.

PMID- 27047021
TI  - Efficacy of pine leaves as an alternative bedding material for broiler chicks
      during summer season.
AB  - AIM: The aim was to assess the efficacy of pine leaves as an alternative bedding
      material on the performance of broiler chicks. MATERIALS AND METHODS: The present
      study was conducted in summer. Total 120, day old Vencobb straight run chicks
      were procured, and after 5 days of brooding, chicks were randomly distributed
      into four treatment groups viz. paddy husk (Group I), paddy straw (Group II),
      pine leaves (Group III), and combination of paddy straw and pine leaves (Group
      IV), each having 30 chicks with 3 replicates of 10 chicks each. Chicks were
      reared under intensive conditions in houses that have a semi-controlled
      environment, with optimum temperature and adequate ventilation. Food and water
      were provided as per NRC (1994) requirement. RESULTS: The average body weight
      after 6 weeks of the experiment was 2018.83+/-31.11, 1983.80+/-33.27, 2007.36+/
      35.73, and 1938.43+/-36.35 g. The bedding type had no significant effect on the
      carcass characteristics viz. evisceration rate and proportion of cut-up parts of
      the carcass except giblet yield. The experiment suggested that performance of
      broiler chicks reared on paddy straw and pine leaves as litter material, had
      improved body weight and feed conversion ratio as compared to rearing on paddy
      husk as bedding material. Bacterial count, parasitic load and the N, P, K value
      of manure of different bedding material shows no significant difference.
      CONCLUSION: Pine leaves have a potential to be used as an alternative source of
      litter material to economize poultry production in a sustainable way, so as to
      make poultry farming as a profitable entrepreneur.

PMID- 27047022
TI  - Clinical and hemato-biochemical studies on fever of unknown origin in buffaloes.
AB  - AIM: The present study was undertaken to ascertain the clinical observation and
      haemato-biochemical studies on fever of unknown origin (FUO) in buffaloes which
      were presented for treatment at the Teaching Veterinary Clinical Complex (TVCC),
      Lala Lajpat Rai University of Veterinary and Animal Sciences (LUVAS), Hisar.
      MATERIALS AND METHODS: The investigation was conducted on total 106 clinical
      cases presented at "TVCC, LUVAS, Hisar." Diseased animals having history of fever
      and increased rectal temperature were considered for the current study. Diagnosis
      of FUO was done on the basis of negative parasitological examination, culture
      examination, fecal and urine test. The cases in which etiology could not be
      established (such as pneumonia, metritis, traumatic reticuloperitonitis, urinary
      tract infection, trypanosomosis, diaphragmatic hernia, Brucellosis, and foreign
      body) were considered as true cases of FUO. RESULTS: Out of 106 clinical cases
      different etiologies were identified in 76 (71.70%) cases including pneumonia,
      traumatic pericarditis, trypanosomosis, bacteremia, etc. and 30 cases (28.30%)
      remained undiagnosed even after detailed investigation. The mean rectal
      temperature (104.43+/-0.16 degrees F), respiration rate (56.57+/-1.51/min) and
      pulse rate (83.40+/-1.77/min) of animals (n=30) suffering from FUO were
      significantly higher, whereas ruminal movement (1.00+/-0.23) was significantly
      lower compared to healthy control group. The mean value of hemoglobin,
      lymphocytes, and packed cell volume were significantly lower, whereas mean value
      of neutrophils was significantly higher compared to that of healthy control
      animals. Mean value of serum levels of glucose, phosphorus, aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase
      (CPK), blood urea nitrogen (BUN), and creatinine were found to be significantly
      higher, whereas mean value of calcium value was significantly lower in all
      clinically affected animals compared to the healthy control group. CONCLUSION:
      About 28.30% cases of fever in buffaloes were found to be of unknown origin.
      Haemato-biochemical findings in cases of FUO in buffaloes revealed relative
      neutrophilia with lymphopenia, hyperglycemia, hypocalcemia, hyperphosphatemia,
      significantly increased AST, ALT, and CPK along with adversely altered kidney
      function indicators (elevated BUN and serum creatinine).

PMID- 27047023
TI  - Evaluation of antigout activity of Phyllanthus emblica fruit extracts on
      potassium oxonate-induced gout rat model.
AB  - AIM: The present study has been conducted to evaluate antigout activity of
      aqueous and alcoholic extracts of Phyllanthus emblica fruits following its 28
      days repeated oral administration on potassium oxonate-induced gout rat model.
      MATERIALS AND METHODS: The study was conducted on 42 male Sprague-Dawely rats
      dividing them in seven groups having six rats in each group. Groups I, II, and
      III served as vehicle control group, gout control group, and standard treatment
      control group, respectively. Rats of all the groups except vehicle control group
      were administered potassium oxonate at 250 mg/kg (IP), throughout the study
      period (28 days) for induction of gout. Groups IV and V received aqueous extract
      of P. emblica at 200 and 400 mg/kg, and Groups VI and VII received alcoholic
      extract of P. emblica at 200 and 400 mg/kg (daily oral for 28 days). At the end
      of study, all the rats were subjected to blood collection; blood and serum sample
      were analyzed for hematological and biochemical parameters, respectively. After
      collection of blood samples on the 29(th) day, all the rats were sacrificed and
      subjected to post mortem examination to determine the presence or absence of
      gross and histopathological lesions in kidney tissues. RESULTS: At the end of
      study, rats of gout control group showed increase in platelets counts, serum
      creatinine, uric acid, blood urea nitrogen (BUN), and xanthine oxidase (XO)
      enzyme level along with alterations in kidney tissues as compared to vehicle
      control group. Gouty rats treated with aqueous and alcoholic extracts of P.
      emblica at 200 and 400 mg/kg body weight and standard treatment allopurinol at 5
      mg/kg body weight showed reduction in platelets counts, serum creatinine, uric
      acid, BUN, and XO enzyme level along with significant improvements in
      histological structure of kidney as compared to rats of gout control group.
      CONCLUSION: Oral administration of aqueous and alcoholic extracts of P. emblica
      fruits for 28 days has shown protection against gout in dose-dependent manner in
      rats.

PMID- 27047024
TI  - A study on the prevalence of Aeromonas spp. and its enterotoxin genes in samples
      of well water, tap water, and bottled water.
AB  - AIM: The aim of this work was to study the prevalence of Aeromonas spp. and its
      enterotoxin genes in various water sources. MATERIALS AND METHODS: 125 samples
      (50 from well water, 50 from tap water, and 25 from bottled water) were collected
      from various sources in and around Greater Hyderabad Municipal Corporation and
      examined for the presence of aeromonads by both cultural and polymerase chain
      reaction (PCR) assay. Alkaline peptone water with ampicillin was used as
      enrichment. Aeromonas isolation medium and ampicillin dextrin agar were used as
      selective media. The boiling and snap chilling method was used for DNA
      extraction. Primers targeted against 16S rRNA, aer, and ast were used to identify
      aeromonads and its enterotoxins. RESULTS: 48%, 18%, and 12% of well water, tap
      water, and bottled water samples were found positive by cultural assay with an
      overall prevalence of 28.8%. Aeromonads were detected in 32 % (52% in well water,
      20% in tap water, and 16% in bottled water) of samples by PCR assay. Aerolysin
      (aer) gene was noticed in 34.6%, 20%, and 0% of well water, tap water, and
      bottled water samples, respectively, with an overall prevalence of 27.5%.
      Thermostable cytotonic enterotoxin (ast) was observed in 37.5% (42.3% in well
      water, 30% in tap water, and 25% in bottled mineral water) of samples.
      CONCLUSIONS: Presence of aeromonads and its toxin genes in various sources of
      water is of public health concern and emphasizes the need for necessary
      preventive measures to tackle the problem.

PMID- 27047025
TI  - Conventional and fluorescent based semen quality assessment in Karan Fries bulls.
AB  - AIM: The present study was carried out on semen ejaculates of 15 Karan Fries (KF)
      bulls maintained at Artificial Breeding Research Centre, National Dairy Research
      Institute, Karnal, India with an objective to evaluate the relationship between
      the conventional and fluorescent based semen quality analysis of the bulls.
      MATERIALS AND METHODS: A total of 96 ejaculates were collected from 15 KF
      (Holstein Friesian [HF] crossbred) bulls. Semen were evaluated for color, volume,
      mass activity (MA) and percentage of individual motility (IM), sperm
      concentration, percent live spermatozoa, hypo-osmotic swelling test and acrosome
      integrity, chromatin integrity, sperm viability, and membrane integrity. Data
      were analyzed using SPSS software package for descriptive analysis. The
      correlation between rankings of sires based on conventional and fluorescent semen
      parameters were calculated by Spearman's rank correlation coefficient. RESULTS:
      The average ejaculates volume (ml), sperm concentration (10(6)/ml), MA, IM (%),
      live (%), morphological abnormalities (%), host (%), acrosome integrity (%),
      chromomycin A3 (CMA3) (%), SYBR-PI (%), and fluorescent isothiocyanate-peanut
      agglutinin (FITC-PNA) (%) were 4.57+/-0.36, 1162.98+/-97.93, 2.95+/-0.09, 60.8+/
      1.22, 71.41+/-2.10, 9.31+/-1.15, 65.5+/-1.81, 86.6+/-1.59, 3.53+/-0.43, 65.39+/
      2.23 and 74.47+/-2.53, respectively. Rank correlations were found to be
      significant for SYBR-PI and FITC-PNA with most of the parameters evaluated by
      conventional methods. Overall, among conventional criteria, IM revealed ranking
      of bulls almost similar to that of fluorescent criteria. CONCLUSION: Overview of
      our results indicated that, among conventional criteria, MA and IM revealed
      ranking of bulls almost similar to that of fluorescent criteria.

PMID- 27047026
TI  - Application of hyaluronic acid in the healing of non-experimental open wounds: A
      pilot study on 12 wounds in 10 client-owned dogs.
AB  - AIM: Veterinarians have frequently to deal with wounds to the skin, subcutis, and
      underlying muscle. The aim was to explore the application of hyaluronic acid (HA)
      containing dressing on open skin wounds in dogs. The progress of healing was
      assessed by wound area reduction and two scoring scales applied in human
      medicine. MATERIALS AND METHODS: Ten client-owned dogs with 12 cutaneous open
      wounds healed by the second intention were included. All wounds were treated
      using available in commerce HA-containing wound dressing from admission to
      complete re-epithelialization. At every clinical examination, wound area and
      scale scoring assessments were performed. RESULTS: After debridement, an
      increased wound size was obtained while an improvement was determined by both
      grading systems. The median numbers of return to the clinic for bandage change
      were 5 times. The median time to complete wound healing was 34.5 days. The mean
      wound area at day 7, 14, 21, and 28 were, respectively, 90.4%, 47.7%, 22.4%, and
      14.8% of the original size (for linear measurement) and 95.5%, 54.4%, 23.10%, and
      14.8% of the original size (for software measurement). Regarding wound healing
      assessment tools, the agreement between two operators was considered high for
      both scales. CONCLUSIONS: HA-containing dressing may be a possible wound
      treatment for cutaneous open wounds in dogs. The assessment of wound quality
      using scale scoring system could be useful especially in the 1(st) week and to
      direct clinical decision-making process.

PMID- 27047027
TI  - Evaluation of Spirulina platensis extract as natural antivirus against foot and
      mouth disease virus strains (A, O, SAT2).
AB  - AIM: This work was aimed to document the antiviral activates of Spirulina
      platensis extract against foot and mouth disease virus (FMDV) different types to
      evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby
      mice. MATERIALS AND METHODS: Cytotoxicity assay studied for S. platensis extract
      on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina
      extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions
      from each mixture were done. FMDV titer for each type of treated FMDV was
      calculated to evaluate the antiviral activity of the Spirulina extract against
      FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml
      intraperitonially from the mixture of FMDV different types and different
      concentration of Spirulina extracts. After 48 h post inoculation, all the baby
      mice examined to evaluate the antiviral action of Spirulina extract. RESULTS: The
      result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%,
      28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells,
      respectively. The same non-toxic dose gave 50% of the inhibitory concentration in
      baby mice without cytotoxic effect. CONCLUSION: This study confirmed the
      biological activity of the ethanol extract of S. platensis against FMDV Types O,
      A, and SAT2. From the results, S. platensis could be useful as antiviral lead to
      limitation of infection among animals during outbreaks but further studies need
      to evaluate the S. platensis on experimental or natural infected farm animals to
      establish the effective dose side affected period of treatment of S. platensis.

PMID- 27047028
TI  - Assessment of semen quality in pure and crossbred Jersey bulls.
AB  - AIM: To compare the seminal attributes of neat, pre-freeze (at equilibration),
      and post-freeze (24 h after freezing) semen in pure and crossbred Jersey bulls.
      MATERIALS AND METHODS: Total 36 ejaculates (3 ejaculates from each bull) were
      collected from 6 pure Jersey and 6 crossbred Jersey bulls and evaluated for
      various seminal attributes during neat, pre-freeze, and post-freeze semen.
      RESULTS: The mean (+/-standard error [SE]) values of neat semen characteristics
      in pure and crossbred Jersey bulls were recorded such as volume (ml), color,
      consistency, mass activity (scale: 0-5), and sperm concentration (millions/ml).
      The extended semen was further investigated at pre-freeze and post-freeze stages
      and the mean (+/-SE) values recorded at neat, pre-freeze, and post-freeze semen
      were compared between pure and crossbred Jersey bulls; sperm motility (80.55+/
      1.70%, 62.77+/-1.35%, 46.11+/-1.43% vs. 80.00+/-1.80%, 65.00+/-1.66%, 47.22+/
      1.08%), live sperm count (83.63+/-1.08%, 71.72+/-1.09%, 58.67+/-1.02% vs. 80.00+/
      1.08%, 67.91+/-1.20%, 51.63+/-0.97%), total abnormal sperm count (8.38+/-0.32%,
      12.30+/-0.39%, 16.75+/-0.42% vs. 9.00+/-0.45%, 12.19+/-0.48%, 18.11+/-0.64%),
      hypo-osmotic swelling (HOS) reacted spermatozoa (71.88+/-0.77%, 62.05+/-0.80%,
      47.27+/-1.05% vs. 72.77+/-1.02%, 62.11+/-0.89%, 45.94+/-1.33%), acrosome
      integrity (89.05+/-0.83%, 81.33+/-0.71%, 71.94+/-0.86% vs. 86.55+/-0.57%, 78.66+/
      0.42%, 69.38+/-0.53%), and DNA integrity (99.88+/-0.07%, 100, 99.66+/-0.11% vs.
      99.94+/-0.05%, 100, 99.44+/-0.18%,). The volume, color, consistency, sperm
      concentration, and initial motility in pure and crossbred Jersey bulls did not
      differ significantly (p>0.05). The mass activity was significantly (p<0.05)
      higher in pure Jersey as compare to crossbred Jersey bulls. Live sperm percentage
      and acrosome integrity was significantly (p<0.01) higher in pure Jersey bulls as
      compared to crossbred Jersey bulls. However, no statistical difference (p>0.05)
      was observed in abnormal sperm; HOS reacted spermatozoa and DNA integrity
      percentage among breeds. CONCLUSION: It may be concluded that the quality of pure
      Jersey bull semen was comparatively better than the crossbred Jersey bulls.

PMID- 27047029
TI  - Ileal and jejunal Peyer's patches in buffalo calves: Histomorphological
      comparison.
AB  - AIM: The present study was aimed to elucidate the histomorphology of ileal and
      jejunal Peyer's patches in the small intestine of buffalo calves and their
      structural comparison. MATERIALS AND METHODS: The study was conducted on neonatal
      (n=10) and pre-pubertal (n=10) buffalo calves. The age of the postnatal buffalo
      calves was estimated by their temporary and permanent dentition. RESULTS: The
      study revealed that several layers of oval to elongate elliptical lymphoid
      follicles were observed in submucosa on the anti-mesenteric side in the ileum of
      early neonatal calves. However, the follicles at this age, in jejunum were of all
      shapes present within one layer. The interfollicular space was occupied by the
      interfollicular tissue, which was diffuse and wider around jejunal lymphoid
      follicles as compared to ileal lymphoid follicles. However, toward the pubertal
      stage, the number of layers of lymphoid follicles was reduced in ileum due to
      involution while it remained similar in number in jejunum at this stage.
      CONCLUSION: The ileal Peyer's patches were found to have started involution more
      or less around reaching puberty, whereas the jejunal Peyer's patches appear to be
      functional throughout the lifespan of the animal.

PMID- 27047030
TI  - Cross antigenicity of immunodominant polypeptides of somatic antigen of
      Oesophagostomum columbianum with other helminths by western blotting.
AB  - AIM: Oesophagostomum columbianum in small ruminants in India is found as mixed
      infection commonly in sheep and goat. Haemonchus contortus, an abomasal nematode
      is found as concurrent infection with it. Eggs of Haemonchus and O. columbianum
      cannot be easily distinguished. Diagnosis of O. columbianum may only be possible
      if a non-cross antigenic polypeptide was available for immunodiagnosis. MATERIALS
      AND METHODS: Somatic antigen (SoAg) of O. columbianum was fractionated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and immunodominant
      polypeptides were identified by western blotting with homologous hyperimmune
      serum (HIS) and experimental sera of sheep or goat infected with other helminths.
      RESULTS: SoAg of O. columbianum was immunoaffinity purified. Sharp polypeptide
      bands of 130, 72 and 68 KDa were observed along with several faint bands of lower
      molecular weight. Western blot of purified SoAg of O. columbianum with homologous
      HIS showed reaction with all the protein bands of 17, 28, 30, 32, 35, 38, 50, 68,
      100, 130, 150, and 170 kDa. For identification of non-cross antigenic
      polypeptide, immunoaffinity purified SoAg of O. columbianum was reacted to
      heterologous HIS against H. contortus, Paramphistomum epiclitum, and Fasciola
      gigantica in western blotting utilizing completely dry method (i-blot). Among
      high molecular weight polypeptides 100 and 150 kDa were non-cross antigenic and
      among low molecular weight except 50 kDa polypeptide, 17, 30, 32, 35, and 38 kDa
      of O. columbianum were not cross antigenic with other helminths. CONCLUSIONS:
      Hence, polypeptides of 17, 30, 32, 35 and 38 kDa as well as 100 and 150 kDa
      polypeptides of O. columbianum may be exploited for immunodiagnosis of the
      infection in sheep and goat with extensive studies on cross antigenicity.

PMID- 27047031
TI  - Development and evaluation of loop-mediated isothermal amplification assay for
      rapid detection of Capripoxvirus.
AB  - AIM: The present study was undertaken to develop a nucleic acid-based diagnostic
      assay loop-mediated isothermal amplification assay (LAMP) targeting highly
      conserved genomic regions of Capripoxvirus (CaPVs) and its comparative evaluation
      with real-time polymerase chain reaction (PCR). MATERIAL AND METHODS: Lyophilized
      vaccine strain of sheeppox virus (SPPV) was used for optimization of LAMP assay.
      The LAMP assay was designed using envelope immunogenic protein (P32) coding gene
      targeting highly conserved genomic regions of CaPV responsible for causing sheep
      pox, goat pox, and lumpy skin disease in sheep, goat and cattle respectively.
      Serial tenfold dilution of SPPV recombinant plasmid DNA was used for a
      calculating limit of detection. Analytical sensitivity and specificity were
      performed. RESULTS: The test described is quick (30 min), sensitive and specific
      for detection of CaPVs. The described assay did not show any cross-reactivity to
      other related viruses that cause apparently similar clinical signs. It was found
      to be ten times more sensitive than conventional PCR however, 100 times less
      sensitive than quantitative PCR (qPCR). LAMP assay results were monitored by
      color change method using picogreen dye and agarose gel electrophoresis.
      CONCLUSION: LAMP assay can be a very good alternative for CaPV detection to other
      molecular techniques requiring sophisticated equipments.

PMID- 27047032
TI  - Exploring the effects of inclusion of dietary fresh Azolla on the performance of
      White Pekin broiler ducks.
AB  - AIM: The objective of this study was to investigate the dietary advantages of
      inclusion of unconventional nutrient source, i.e., Azolla in the basal diet of
      White Pekin broilers. MATERIALS AND METHODS: All ducklings were randomly
      distributed into three treatment groups with three replicates each and each
      replicate having 12 ducklings and were reared in deep litter system. Groups were
      subjected to three dietary treatments such as G1: Basal diet, G2: Basal diet + 5%
      fresh Azolla of basal diet, G3: Basal diet + 10% fresh Azolla of basal diet.
      During experimental period, parameters, such as bodyweight, bodyweight gain, feed
      consumption,feed conversion ratio(FCR), and economic of production,wererecorded.
      RESULTS: The result showed that body weights in every week, except the 5(th)
      week, did not differ significantly between groups. However, no significant
      difference was observed between the groups in any week in terms of absolute body
      weight gain and feed consumption. As regard to FCR, the 10% Azolla group (G3)
      showed the best feed efficiency followed by the 5% Azolla group (G2) and the
      control group (G1). On the basis of profit/bird or profit/kg live weight, each of
      the Azolla-fed group showed a higher economic efficiency than the control.
      CONCLUSION: From the experiment, it was concluded that Azollaat 5 or 10% level
      can be included in the diet to economize the White Pekin broiler farming, and it
      can be great impetus to poultry farming to include unconventional nutrient source
      as a dietary supplement.

PMID- 27047033
TI  - Prevalence and epidemiology of Salmonella enterica serovar Gallinarum from
      poultry in some parts of Haryana, India.
AB  - AIM: The present study was investigated to ascertain the epidemiological status
      of fowl typhoid (FT) in broilers in some parts of Haryana during January 2011 to
      December 2013. MATERIALS AND METHODS: To elucidate the epidemiological status of
      FT in broiler chickens for the 3 years (2011-2013) and to study the prevalence of
      various Salmonella serovars in poultry on the basis of culture characteristics,
      biochemical features, serotyping, and their antibiogram profile from some parts
      of Haryana (India). RESULTS: A total of 309 outbreaks of FT were recorded in
      chickens during this period. Overall percent morbidity, mortality, case-fatality
      rate (CFR) in broiler chicks due to FT during this period was 9.45, 6.77, and
      71.55. The yearly observations were divided into quarters A (January-March), B
      (April-June), C (July-September) and D (October-December). Maximum number of
      outbreaks - 106 (34.3%) was recorded in quarter D followed by quarters B - 84
      (27.3%), C - 64 (20.7%), and A - 55 (17.7%). Salmonella isolates (253) were
      recovered from disease outbreaks in broilers from different parts of Haryana.
      Typical morphology and colony characters on MacConkeys Lactose Agar and Brilliant
      Green agar, biochemical reactions, serotyping along with antibiogram profiles
      were able to group these isolates into 3 groups namely Salmonella Gallinarum
      (183), Salmonella Enteritidis (41) and Salmonella Typhimurium (29). The
      antibiogram pattern of 183 isolates of S. Gallinarum revealed that most of the
      isolates were sensitive to gentamicin (76%) followed by amikacin (72%), kanamycin
      (71%). CONCLUSION: FT is prevalent in commercial broiler flocks in different
      parts of Haryana and is responsible for considerably high morbidity and mortality
      in affected flocks. Isolation of S. Gallinarum (9, 12:183) from FT cases suggest
      it to be the primary pathogen, however, isolation of S. Typhimurium and S.
      Enteritidis from these cases is a major concern. The detection of S. Enteritidis
      and S. Typhimurium from FT cases assumes significance from public health point of
      view.

PMID- 27047034
TI  - Therapeutic management of botulism in dairy cattle.
AB  - AIM: To report the successful recovery of few dairy cattle from botulism in
      response to a modified therapeutic strategy. MATERIALS AND METHODS: Seventy four
      naturally-occurring clinical cases of bovine botulism encountered during the
      period of 2012-2014 which were confirmed by mouse lethality test became material
      for this study. Affected animals were made into three groups based on the
      treatment modifications made during the course of study. RESULTS AND DISCUSSION:
      With the modified therapeutic regimen, 17 animals recovered after 7-10 days of
      treatment. Clinical recovery took 2-30 days. Animals which were not given
      intravenous fluid and calcium recovered uneventfully. Cattle which were already
      treated with intravenous fluids, calcium borogluconate, and antibiotics did not
      recover. They were either died or slaughtered for salvage. CONCLUSION: In cattle
      with botulism, administration of Vitamin AD3E and activated charcoal aid the
      clinical recovery. Besides, strictly avoiding anti-clostridial antibiotics, fluid
      therapy, and calcium therapy may facilitate the clinical recovery. Upon fluid
      administration, the pulmonary congestion existed in the ailing cattle might have
      worsened the anoxia. Administration of antibiotics like penicillin,
      aminoglycosides, and tetracyclines further worsen the neuronal paralysis by
      increasing the availability of botulinum neurotoxin. Cattle in early botulism
      have fair chances of recovery with the modified therapy.

PMID- 27047035
TI  - Comparative efficacy of different estrus synchronization protocols on estrus
      induction response, fertility and plasma progesterone and biochemical profile in
      crossbred anestrus cows.
AB  - AIM: To evaluate estrus induction response and fertility including plasma
      progesterone and biochemical profile following use of three standard hormonal
      protocols in anestrus crossbred cows. MATERIALS AND METHODS: The study was
      carried out on 40 true anestrus and 10 normal cyclic cows. 10 anestrus cows each
      were treated with standard intravaginal controlled internal drug release (CIDR)
      device, Ovsynch (GPG) protocol, and Norgestomet ear implant with fixed-time
      artificial insemination (FTAI). 10 anestrus cows were kept as untreated control
      while 10 cows exhibiting the first estrus within 90 days postpartum without any
      treatment served as normal cyclic control. Blood samples were obtained from
      treated cows on day 0, 7, 9 (AI) of treatment and day 21 post-AI, and from
      control groups on the day of AI and day 21 post-AI for estimation of plasma
      progesterone, protein, cholesterol, calcium, and inorganic phosphorus profile.
      RESULTS: The use of CIDR, Ovsynch, and Norgestomet ear implant protocols resulted
      in 100% estrus induction with conception rates at induced estrus of 60%, 50%, and
      50%, and the overall of three cycles as 80%, 80%, and 70%. In untreated anestrus
      control (n=10), only three cows exhibited spontaneous estrus within 90 days of
      follow-up and conceived giving the first service and overall conception rates of
      66.66% and 30.00%, respectively. In normal cyclic control (n=10), the conception
      rates at first and overall of three cycles were 50% and 80%. The overall mean
      plasma progesterone (P4) concentrations in anestrus cows studied on day 0
      (initiation), 7 (prostaglandin injection and/or removal of implant), 9 (FTAI) of
      treatment and on day 21 post-AI revealed that the values on day 7 and 21 were
      significantly (p<0.01) higher than other two periods in all three groups. The
      concentrations were significantly (p<0.05) higher in conceived than non-conceived
      group on day 21 post-AI in CIDR (4.36+/-0.12 vs. 1.65+/-0.82 ng/ml) and Ovsynch
      (4.85+/-0.62 vs. 1.59+/-0.34 ng/ml), but not in Norgestomet ear implant (4.50+/
      0.53 vs. 3.02+/-1.15 ng/ml) or normal cyclic group (5.39+/-0.67 vs. 3.13+/-0.37
      ng/ml). The cholesterol and protein levels were significantly higher, but not the
      calcium and phosphorus, in normal cyclic control than in anestrus groups. The
      influence of treatment days and pregnancy status was not significant for any of
      the biochemical constituents in any of the groups. CONCLUSION: Ovsynch and/or
      CIDR synchronization protocol can be effectively used to improve fertility up to
      80% in anestrus cows, as compared to 30% in anestrus control, combined with
      plasma progesterone to delineate the reproductive status before and after
      treatment.

PMID- 27047036
TI  - Electrocardiogram pattern of some exotic breeds of trained dogs: A variation
      study.
AB  - AIM: The present study has been conducted to evaluate the variation in
      electrocardiogram (ECG) parameters among different trained breeds of dogs (viz.
      Labrador, German Shepherd, and Golden Retriever) used for security reasons.
      MATERIALS AND METHODS: The ECG was recorded by single channel ECG at a paper
      speed of 25 mm/s and calibration of 10 mm=1 mV. The recordings were taken from
      all the standard bipolar limb leads (Lead-I, II, and III) and unipolar augmented
      limb leads (Lead-aVR, aVL, and aVF). RESULTS: Heart rate was found to be highest
      in Labrador and lowest in German Shepherd. P-wave duration was maximum in Golden
      Retriever breed and lowest in Labrador. Maximum amplitude of P-wave was found in
      Labrador followed by German Shepherd and Golden Retriever. There was
      significantly (p<0.05) higher values of PR interval in German Shepherd compared
      to other breeds. The variation in QRS duration, ST segment duration, T-wave
      duration, and T-wave amplitude was found to be non-significant among breeds.
      Inverted T-waves were most common in Golden Retriever and German Shepherd,
      whereas positive T-waves were found in Labrador. There was significant (p<0.05)
      variation in mean electrical axis of QRS complex among different breeds and it
      ranges from +60 degrees  to +80 degrees . CONCLUSION: The present study provides
      the reference values for different ECG parameters to monitor the cardiac health
      status among Labrador, German Shepherd, and Golden Retriever breeds.

PMID- 27047037
TI  - Staining of Platyhelminthes by herbal dyes: An eco-friendly technique for the
      taxonomist.
AB  - AIM: An environment compatible technique to stain Platyhelminthes, Fasciola
      gigantica, Gastrothylax crumenifer, Taenia solium, and Moniezia expansa using
      aqueous and alcoholic extract of sugar beet (Beta vulgaris), China rose (Hibiscus
      rosa-sinensis), and red rose (Rosa hybrida) were described to minimized the
      deleterious effects of the synthetic dyes. MATERIALS AND METHODS:
      Aqueous/ethanolic extracts of roses were extracted from the flowers while red
      beet was extracted from the roots. RESULTS: Stained helminthes acquired a
      comparable level of pigmentation with the distinction of their internal structure
      in these natural dyes. The flukes (liver and rumen) internal structure, oral and
      ventral/posterior sucker, cirrus sac, gravid uterus, testes, ovary, and
      vitallaria were appeared pink color in aqueous and alcoholic extract of either
      China or red rose and yellow to brown color in sugar beet stain. The interior of
      the proglottid of T. solium and M. expansa took yellow to brown color with good
      contrast in sugar beet stain and of pink to pink-red in China and red rose stain.
      CONCLUSION: The extract of roses (red rose followed by China rose) followed by
      red beet possess the potential to replace the conventional stains in the
      taxonomic study of Platyhelminthes parasites.

PMID- 27047038
TI  - A retrospective study on findings of canine hip dysplasia screening in Kenya.
AB  - AIM: The current study was undertaken to evaluate the findings of canine hip
      dysplasia screening in Kenya. MATERIALS AND METHODS: Records for 591 dogs were
      included in this study. The data was obtained from the national screening office,
      Kenya Veterinary Board, for the period between the years 1998 and 2014. Monthly
      screening records were assessed and information relating to year of evaluation,
      breed, sex, age, and hip score captured. Descriptive statistics of hip scores was
      computed based on year, sex, age, and breed. RESULTS: A total of 591 records from
      the year 1998 to 2014 were retrieved at the National Screening Centre, the Kenya
      Veterinary Board. Each record was examined and data pertaining to year of
      screening, the breed, sex, age of the dogs, and the total hip score were
      recorded. The highest number of dogs screened for hip dysplasia (HD) was in the
      year 2009 and the lowest in the year 1998. More females than males were screened
      for HD and the mean age of all the dogs was 22.9+/-12.7 months. The most common
      breeds of dogs screened during the study period were German Shepherd (67.0%),
      Rottweiler (15.6%), and Labrador Retriever (12.2%). The mean hip score for the
      591 dogs was 15.1+/-10.9 and the median 12.0. The mean hip scores per breed were;
      German Shepherd (16.3+/-12.1); Golden Retriever (16.0); Hungarian Vizla (15.0);
      Labrador Retriever (3.0+/-6.7); Great Dane (13.3+/-3.2); Rottweiler (12.2+/-8.2);
      Doberman (10.3+/-4.2); Rhodesian Ridgeback (9.6+/-3.8); and Boxer (9.3+/-0.6).
      Based on the hip score, moderate to severe HD was diagnosed in 16.6% of the dogs,
      mild HD in 32.7%, Borderline HD in 37.7%, fair HD in 6.9%, and good HD in 6.1%.
      CONCLUSION: Canine HD is a common occurrence in Kenya with most dogs suffering
      mild to border line HD. In addition, German Shepherd and Golden Retriever appear
      to be the most affected breeds. It is therefore recommended that stringent
      measures be imposed to dog breeding programs to avoid transmission of this
      undesirable trait and consequently improve the welfare and the quality of dog
      breeds in Kenya.

PMID- 27047039
TI  - Histopathological and immunohistochemical diagnosis of infectious bursal disease
      in poultry birds.
AB  - AIM: The aim of the present study was to diagnose infectious bursal disease (IBD)
      using gross, histopathological, and immunopathological approaches and to compare
      efficacy of immunohistochemical techniques with conventional diagnostic
      techniques. MATERIALS AND METHODS: A total of 33 samples were collected from the
      six different poultry farms from Ludhiana and the nearby districts. Upon gross
      analysis of the necropsied birds, the relevant tissue samples such as bursa,
      kidney, junction of proventriculus and gizzard, heart, and muscles were then
      processed for histopathological and immunohistochemical studies. RESULTS: Varied
      macroscopic changes were noted in bursa, characterized as swollen, hemorrhages to
      atrophy in size. Nonetheless, hemorrhages over thigh muscles were rarely seen.
      Histologically, the bursa showed prominent fibrotic and atrophic changes.
      Rarefaction of bursal follicles with intermittent infiltration of lympho
      mononuclear cells with chronic cystic changes was additional changes, considered
      to be paramount for IBD. Expression and localization of IBD specific viral
      antigens were noticed mainly intracellular to the rarefied areas of bursal
      follicle section(s), in conjunction to inner lining of the cystic cavities of
      affected follicles. In addition, the junction of proventriculus and gizzard, the
      heart muscle, respiratory ciliated epithelium, and proventriculus also revealed
      positive expression to IBD virus (IBDV) antigen. Advanced immunopathological
      techniques, i.e., immunofluorescence further testified the evidence of antigen as
      positive green signal within affected follicles. Further consideration to the
      reliability of various techniques employed, positive correlation (r=0.64623) was
      emerged out with conventional pathological scoring. CONCLUSION: It is concluded
      that the bursa acts as an organ of choice for demonstrating IBDV antigen for
      specific diagnosis of disease using immunohistochemistry (IHC), and IHC staining
      is a precise, specific, rapid, and reliable method to demonstrate the IBDV
      antigen in the altered tissues due to IBDV infection.

PMID- 27047040
TI  - Biochemical studies in experimentally Escherichia coli infected broiler chicken
      supplemented with neem (Azadirachta indica) leaf extract.
AB  - AIM: An experimental study was conducted on 192-day-old broiler chicks for
      evaluating the effect of 10% neem leaf extract (NLE) supplementationon
      biochemical parameters in chickens experimentally infected with Escherichia coli
      O78 at 10(7) CFU/0.5 ml at 7 days of age. MATERIALS AND METHODS: The 192-day-old
      broiler chicks were procured. These chicks were divided into two groups (A and B)
      containing 96 birds each on the 1(st) day. Diet of all the chicks of Group A was
      supplemented with 10%NLE in water, whereas chicks of Group B were given feed and
      water devoid of NLE supplementation throughout the experiment. After rearing for
      1 week, chicks of both the groups (A and B) were again divided into two subgroups
      (Group A into A1 and A2 and Group B into B1 and B2) of 54 and 42 birds,
      respectively. At the age of 7 days all the chicks of groups A1 and B1 were
      injected with E. coli O78 at 10(7) CFU/0.5 ml intraperitoneally. Blood samples
      were collected from six chicks from each group at day 0, 2, 4, 7, 14, 21, 28 days
      post-infection and serum was separated for biochemical studies. RESULTS: There
      was a significant increase in serum alanine transaminase (ALT), aspartate
      transaminase (AST), lactate dehydrogenase (LDH) activities, globulin
      concentration and a decrease in total protein (TP), albumin concentrations, and
      alkaline phosphatase (ALP) activity in both the infected groups. However, the
      changes in biochemical values, i.e., ALT, AST, LDH, ALP, TP, albumin, and
      globulin wereof lower magnitude in NLE supplemented group suggesting
      hepatoprotective and cardioprotective effect of NLE. CONCLUSIONS: Fromthe present
      study, it is reasonable to conclude that significant increase in the value of
      ALT, AST, LDH, globulin, and significant decrease in the value of ALP, TP, and
      albumin was of lower magnitude in supplemented infected group (A1) as compared to
      non-supplemented infected group (B1) suggesting hepatoprotective and
      cardioprotective effect of NLE.

PMID- 27047041
TI  - Clinicopathological evaluation of non-parasitic dermatoses in canines.
AB  - AIM: The present study has been carried out to detect non-parasitic dermatoses in
      canines brought at the Nandini Veterinary Hospital, Surat. MATERIALS AND METHODS:
      The current investigation was carried out on skin scrapping, skin biopsy
      specimens, blood, and serum samples of 210 freshly registered cases of dogs with
      dermatological afflictions. Dogs found healthy on clinical examination were used
      as control animals (n=15). The incidence of non-parasitic dermatoses has been
      recorded as per age, breed, and sex of dogs. For bacterial isolation, the
      pus/exudates samples were collected from 40 cases of pyoderma and streaked onto
      brain-heart infusion agar while 13 skin scrapping samples were inoculated on
      Sabouraud's dextrose agar with chloramphenicol for isolation of fungi. The
      organisms were identified on the basis of gross and microscopic observation of
      cultural growth on media. The blood and sera samples were also collected to note
      alteration in hematology and biochemical parameters, respectively. Tissue samples
      from lesions were collected and subsequently preserved in 10% neutral buffered
      formalin for histopathology. RESULTS: Out of 210 cases of dermatoses, 60 cases
      were of non-parasitic dermatoses, i.e., 28.57%. Of these, bacterial skin
      infections (pyoderma) were found to be the predominant at 80.00%, followed by
      other non-parasitic dermatological disorders, i.e., 11.67% and fungal skin
      infection, i.e., 8.33%. The dogs belonging to age group 1-3 years showed greater
      susceptibility to non-parasitic dermatological conditions. Breed wise incidence
      of pyoderma was found more in the Pomeranian breed (20.83%), whereas fungal skin
      affections were found to be higher in mongrel breed (60.00% and 42.86%,
      respectively). Male dogs showed greater involvement in bacterial, fungal, and
      other non-parasitic dermatoses. Bacteriological culture examination of 40 pus
      swabs resulted in the growth of 39 bacterial isolates. Mycological culture of
      skin scrapings from 13 suspected cases of fungal dermatoses resulted in the
      recovery of five fungal isolates. Hematological and serum biochemical parameters
      revealed a significant difference in all cases of non-parasitic
      dermatoses.Histopathological study revealed characteristic changes like
      infiltration of neutrophils with perifolliculitis, hyperkeratosis, and rafts of
      acantholytic cells. Histochemical staining revealed purple or magenta color
      fungal elements. CONCLUSION: Based on current experiment it has been concluded
      that among non-parasitic dermatoses bacterial and fungal skin infections are the
      main ailments, followed by nutritional and other causes in adult and male dogs
      which can be diagnosed by cultural inoculation, microscopic examination of skin
      scrapings, and dermatohistopathology along with hematology and biochemistry.

PMID- 27047042
TI  - The effects of protein dietary supplementation on fecal egg counts and
      hematological parameters in goat kids with subclinical nematodosis.
AB  - AIM: The aim of the present study was to assess the effect of dietary
      supplementation with different levels of protein on fecal egg counts and
      hematological parameters in goat kids with subclinical nematodosis under semi
      intensive condition. MATERIALS AND METHODS: 20 goat kids (3-5 months old with an
      average body weight of 8.90 kg) were randomly allocated to four groups: T1,
      served as a negative control, without receiving concentrate feed, and T2, T3, and
      T4 that received concentrate feed containing 16, 20, and 24% digestible crude
      protein, respectively. The experiment was carried out for 60 days. RESULTS: In
      this study, protein supplementation had a significant (p<0.05) effect on fecal
      egg counts even after 15 days; hemoglobin (Hb) (g/dl) after 45 days; total
      leukocyte count (10(3)/mm(3)) and total erythrocyte count (10(6)/mm(3)) after 30
      days; packed cell volume (%), lymphocyte (%), and eosinophil (%) after 15 days of
      supplementation, whereas monocyte (%) and neutrophil (%) values were not
      significantly influenced by protein supplementation effect during the entire
      experiment. The values of mean corpuscular volume (fl) were affected
      significantly (p<0.05, p<0.01) due to protein supplementation after 30 days, mean
      corpuscular Hb (MCH) (pg) after 45 days, but MCH concentration (g/dl) was not
      significantly different among the experimental groups during the entire
      experiment. CONCLUSION: The dietary supplementation with different levels of
      protein significantly improved the hematological profiles and inhibited the
      nematodosis infection in the experimental goat kids.

PMID- 27047043
TI  - Genetic and non-genetic factors affecting morphometry of Sirohi goats.
AB  - AIM: The aim was to estimate genetic and non-genetic factors affecting
      morphometric traits of Sirohi goats under field condition. MATERIALS AND METHODS:
      The detailed information of all animals on body measurements at birth, 3, 6, 9,
      and 12 months of age was collected from farmer's flock under field condition born
      during 2007-2013 to analyze the effect of genetic and non-genetic factors. The
      least squares maximum likelihood program was used to estimate genetic and non
      genetic parameters affecting morphometric traits. RESULTS AND DISCUSSION: Effect
      of sire, cluster, year of birth, and sex was found to be highly significant
      (p<0.01) on all three morphometric traits, parity was highly significant (p<0.01)
      for body height (BH) and body girth (BG) at birth. The h(2) estimates for
      morphometric traits ranged among 0.528+/-0.163 to 0.709+/-0.144 for BH, 0.408+/
      0.159 to 0.605+/-0.192 for body length (BL), and 0.503+/-0.197 to 0.695+/-0.161
      for BG. CONCLUSION: The effect of sire was highly significant (p<0.01) and also
      h2 estimate of all morphometric traits were medium to high; therefore, it could
      be concluded on the basis of present findings that animals with higher body
      measurements at initial phases of growth will perform better with respect to even
      body weight traits at later stages of growth.

PMID- 27047044
TI  - Effect of Moringa oleifera on hematological parameters of calves reared in
      industrial fluorotic area.
AB  - AIM: The present study was undertaken to evaluate the ameliorative potential of
      dried Moringa oleifera fruit powder in fluorosis affected calves reared around
      the vicinity of aluminium smelter plant. MATERIALS AND METHODS: Total 107 calves
      were screened on the basis of clinical signs and higher plasma fluoride (more
      than 0.2 ppm) level for evidence of fluorosis. Out of that, 90 samples found
      positive and from them 18 calves of 6-12 months age group were selected and
      divided equally into three groups named as Group II, III, and IV. Group II
      remained as disease control group whereas Group III calves were supplemented with
      dried M. oleifera fruit powder of 25 g/calve for 60 days. Group IV calves were
      supplemented with calcium carbonate at 100 mg/kg body weight and boric acid at 10
      mg/kg for the same experimental period. Group I consisted of six numbers of
      healthy calves taken from the non-fluorotic zone, i.e. Bhubaneswar. Plasma
      fluoride level, hemoglobin (Hb), packed cell volume (PCV), total leukocyte count
      (TLC), differential count (DC), total erythrocyte count, mean corpuscular volume
      (MCV), mean corpuscular Hb (MCH), and MCH concentration (MCHC) were estimated on
      day 0, 30, and 60 of the experiment. RESULTS: Supplementation of dried M.
      oleifera fruit powder to fluorosis affected calves resulted in significant
      reduction in plasma fluoride level and increase in Hb%, PCV, TLC and altered DC.
      Similar results were also recorded in calcium+boron group, except PCV and Hb. No
      significant changes were observed in MCV, MCH, and MCHC values. CONCLUSION: The
      present study concluded that supplementation of dried M. oleifera fruit powder
      daily for 60 days has shown protection against chronic fluoride toxicity in
      calves.

PMID- 27047045
TI  - Comparison of molecular and microscopic technique for detection of Theileria
      annulata from the field cases of cattle.
AB  - AIM: Tropical theileriosis is fatal hemoprotozoal disease of dairy animals caused
      by Theileria annulata. The aim of the present study was to detect the T. annulata
      and comparison of results of molecular and microscopic techniques. MATERIALS AND
      METHODS: A total of 52 blood samples were collected from the cattle suspected for
      theileriosis across the Banaskantha district. All the samples were screened for
      theileriosis using Giemsa's staining technique and polymerase chain reaction
      (PCR). RESULTS: Total of 17 (32.69%) and 24 (46.15%) samples were found positive
      for theileriosis by microscopic examination and PCR test, respectively. It
      revealed that the study area is endemic for theileriosis, and the microscopic
      technique has 70.83% sensitivity and 100% specificity with respect to PCR
      technique. CONCLUSION: It may be concluded from the present study that the PCR is
      comparatively sensitive technique than microscopic examination and may be
      recommended to use in the field for screening of theileriosis in the study area,
      where a high prevalence of diseases have been reported due to intensive dairy
      farming.

PMID- 27047046
TI  - Effect of age and season on the thyroid hormone activity of Mizoram strain female
      mithun (Bos frontalis).
AB  - AIM: The aim of the present study was to generate baseline data on the normal
      values of the thyroidhormone (TH) activity as well as their correlation with age
      and season. MATERIALS AND METHODS: Blood samples (10 ml) were collected from
      jugular vein of 30 female mithun's of three different age groups viz. Calves (6
      months to 1 year), heifer (1-3 years) and adult (above 3 years) during the three
      season's viz. Monsoon, winter and spring of a year. The serum was analyzed for
      thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4)
      activity. RESULT: The result showed a significantly (p<0.05) a higher T3 level in
      heifers followed by adults and calves and higher T4 level in adults followed by
      heifers and calves in all the seasons. The TSH level was higher in heifers in all
      the seasons. The winter season recorded higher level of T3, T4, and TSH as
      compared to the other seasons of a year. CONCLUSION: The TSH and T3 level were
      the highest for aheifer, whereas T4 level was the highest for adults inall the
      season. Furthermore, the higher level of TH was observed in winter season. The
      increased level of the TH during the winter season signifies their calorigenic
      effect. Similarly in heifers, the increased T3 concentrations show its importance
      in reproductive physiology and its association with ovarian activity. This
      indicates that age and season have aprofound effect on TH activity of Mizoram
      strain female mithun.

PMID- 27047047
TI  - Flow cytometry based profiling of leukocytes: A new method for diagnosis of
      tropical theileriosis in crossbred cattle.
AB  - AIM: In India, dairy industries are important for the livelihood of small scale
      farmers and dairy owners. Tropical theileriosis, mostly affecting dairy cattle
      and buffaloes is a major threat to dairy and related industries. Tropical
      theileriosis is caused by Theileria annulata, a hemoprotozoan parasite
      transmitted by Ixodid ticks of Hyalomma spp. In the present study, we examined
      the clinical signs, hematological parameters and flow cytometric profile of whole
      blood in 30 theileriosis affected crossbred cattle. The aim of our study is to
      analyze, in comparison with clinical and hematological diagnosis, whether flow
      cytometry based profiling of leukocytes could be used as better, quick and
      alternative method for diagnosis and screening of bovine tropical theileriosis in
      crossbred cattle. MATERIALS AND METHODS: In this study, we screened parasites in
      30 peripheral blood samples from clinical cases of theileriosis by Giemsa's
      staining technique in crossbred cattle. Hematological analysis was done to
      estimate hemoglobin (Hb) content, total red blood cell (RBC) count, total
      leukocyte count and differential leukocyte count. Further, flow cytometric
      analysis of whole blood was carried out to study leukocytes profile in affected
      cattle. RESULTS: Microscopic examination of stained blood films revealed the
      presence of piroplasms in erythrocytes and schizonts in lymphocytes.
      Hematological examination revealed significant (p<0.05) decrease of Hb percent
      (Hb %), reduced total RBC and total leukocytes, lymphocytosis, eosinopenia, and
      neutropenia compared to that of apparently healthy cattle. Flow cytometric
      profiling of leukocytes revealed the severe effect on shape, size, and
      granularity of leukocytes, marked decrease in granulocytes and 3-5 fold increase
      in lymphocytes count compared to clinically healthy cattle. Thus, in both
      methods, namely conventional and flow cytometric analysis, marked lymphocytosis
      and decrease in other blood cell counts were observed compared to clinically
      healthy cattle. CONCLUSIONS: From results, it can be concluded that though
      conventional staining techniques and hematology are efficient in diagnosis of
      theileriosis, leukocytes profiling based on flow cytometry combined with clinical
      examination could be a quick, novel and alternative method for diagnosis and
      screening of clinical tropical theileriosis in crossbred cattle. Thus, there is
      potential to offer a flow cytometry based diagnostic service for tropical
      theileriosis in crossbred cattle.

PMID- 27047048
TI  - Effect of cholesterol supplementation on cryosurvival of goat spermatozoa.
AB  - AIM: Sperm membrane cholesterol influences cryodamage during cryopreservation.
      The present study was carried out to evaluate the effect of varying cholesterol
      levels in Tris based extenders on the freezability of sexually healthy Malabari
      buck semen. MATERIALS AND METHODS: A total of 48 ejaculates from two adults
      healthy sexually healthy Malabari bucks were utilized for the study. The
      collected and pooled ejaculates were divided into four groups with Group I
      serving as Control - I, Group II and III were treated with 1 mg and 2 mg of
      cholesterol-loaded-cyclodextrin (CLC)/120 * 10(6) spermatozoa, respectively, and
      Group IV, treated with 1 mg methyl-beta-cyclodextrin (MbetaCD) served as Control 
      II. Manual freezing was carried out to cryopreserve the treated and control
      spermatozoa. RESULTS: Treatment of semen samples with CLC resulted in improved
      maintenance of sperm motility at pre-freeze and post-thaw stages of
      cryopreservation without affecting hypo-osmotic swelling response. Treatment of
      semen with 1 mg of CLC/120 * 10(6) spermatozoa was observed to be better than
      treatment with 2 mg of CLC/120 * 10(6) spermatozoa. In general, MbetaCD treatment
      was found to result in significantly lower sperm characteristics than those of
      Control - I and CLC treatment at pre-feeze and post-thaw stages and when
      incubated up to 4 h. CONCLUSION: Cholesterol treatment of sexually healthy
      Malabari buck semen was found to hold promise for improving cryopreservability of
      spermatozoa.

PMID- 27047049
TI  - Evaluation of antidiarrheal activity of ethanolic extract of Holarrhena
      antidysenterica seeds in rats.
AB  - AIM: The present study was conducted to evaluate the antidiarrheal effect of
      ethanolic extract of Holarrhena antidysenterica (Family - Apocynaceae) seeds
      against induced diarrhea in Wistar albino rats. MATERIALS AND METHODS: The
      extract was evaluated for castor oil and Escherichia coli induced diarrhea.
      Extract was given at 100, 200, 400 mg/kg body wt. orally in both protocols.
      Standard antidiarrheal Loperamide was used at 5 mg/kg body wt. orally in castor
      oil induced protocol, while standard antibiotic Gentamicin at 8 mg/kg body wt.
      intraperitoneally was used in E. coli induced diarrhea. In castor oil induced
      protocol, the percentage inhibition of defecation was calculated for each group,
      whereas in E. coli induced protocol, change in fecal consistency, and body weight
      was recorded for each individual rat for 3 days. RESULTS: The severity of castor
      oil induced diarrhea was reduced significantly (p<0.05) with H. antidysenterica
      seeds extract at 200 and 400 mg/kg body wt. which showed equivalent effectiveness
      like that of Loperamide treated groups. Similarly in E. coli induced diarrhea
      protocol, the mean change in body weight was significantly (p<0.05) higher in
      positive control, whereas no significant variation was observed in negative
      control, Gentamicin treated and H. antidysenterica treated group at 200 mg/kg and
      400 mg/kg body wt., respectively. CONCLUSION: The study concluded that ethanolic
      extract of H. antidysenterica seeds effectively controlled diarrhea and decreased
      the severity of clinical signs of castor oil and E. coli induced diarrhea in
      Wistar rats.

PMID- 27047050
TI  - Assessment of aflatoxin B1 in livestock feed and feed ingredients by high
      performance thin layer chromatography.
AB  - AIM: Detection of aflatoxin B1 in Livestock compound Feed and feed ingredients by
      high-performance thin layer chromatography (HPTLC). MATERIALS AND METHODS:
      Chromatography was performed on HPTLC silica gel 60 F 254, aluminum sheets by
      CAMAG automatic TLC sampler 4, with mobile phase condition
      chloroform:acetone:water (28:4:0.06). Extraction of aflatoxin B1 from samples was
      done as per AOAC method and screening and quantification done by HPTLC Scanner 4
      under wavelength 366 nm. RESULTS: A total of 97 livestock feed (48) and feed
      ingredients (49) samples received from different livestock farms and farmers were
      analyzed for aflatoxin B1of which 29 samples were contaminated, constituting 30%.
      Out of 48 livestock compound feed samples, aflatoxin B1 could be detected in 16
      samples representing 33%, whereas in livestock feed ingredients out of 49
      samples, 13 found positive for aflatoxin B1 representing 24.5%. CONCLUSION: HPTLC
      assures good recovery, precision, and linearity in the quantitative determination
      of aflatoxin B1 extracted from Livestock compound feed and feed ingredients. As
      more number of feed and feed ingredients are contaminated with aflatoxin B1 which
      causes deleterious effects in both animal and human beings, so there is a need
      for identifying the source of contamination, executing control measures, enabling
      better risk assessment techniques, and providing economic benefits.

PMID- 27047051
TI  - Detection of genes mediating beta-lactamase production in isolates of
      enterobacteria recovered from wild pets in Saudi Arabia.
AB  - AIM: To determine the genetic basis and types of beta-lactamase encountered among
      enterobacterial isolates of wild pets from the animal exhibit. MATERIALS AND
      METHODS: A total of 17 beta-lactamase-producing enterobacteria recovered from
      fecal samples of wild pet animals were analyzed for a selected beta-lactamase
      gene by polymerase chain reaction. RESULTS: Molecular analysis identified one or
      more beta-lactamase-encoding genes in 14 enterobacterial isolates as a single or
      gene combination. The most frequent extended-spectrum beta-lactamases types were
      TEM and CTX-M, and the most common AmpC enzymes were CMY-2 and DHA types.
      CONCLUSIONS: The study is the first in Saudi Arabia, have established the
      presence of beta-lactamase-encoding genes in the fecal isolates of wild pets.

PMID- 27047052
TI  - Study on prevalence of ancylostomosis in dogs at Anand district, Gujarat, India.
AB  - AIM: This study was undertaken to derive the prevalence rate of ancylostomosis in
      dogs by a collection of fecal samples from Anand district. MATERIALS AND METHODS:
      The fecal samples were collected from the dogs brought to the Hospital of
      Veterinary College (Teaching Veterinary Clinical Service Complex) and the
      surrounding areas of Anand district. On the day of collection, fecal samples were
      collected and brought to the Department of Veterinary Parasitology and processed
      for standard qualitative examination. The sedimentation technique was used to
      detect the presence of Ancylostoma spp. eggs in the samples. RESULT: The highest
      prevalence rate was observed in the month of May (36.66% fecal samples) and the
      lowest in the month of December (13.79% fecal samples) at Anand district.
      CONCLUSION: It can be concluded that heavy infection is present in Anand district
      especially in the season of summer followed by monsoon and the least in winter.

PMID- 27047053
TI  - Feasibility of C-arm guided closed intramedullary pinning for the stabilization
      of canine long bone fractures.
AB  - AIM: To evaluate the feasibility of C-arm guided closed intramedullary pinning
      (simple Steinmann and end threaded) techniques for the stabilization of various
      canine long bone fractures. MATERIALS AND METHODS: The present study was
      conducted on 19 dogs with long bone fractures which were stabilized using simple
      Steinmann (Group I; n=6) and end threaded (Group II; n=13) pinning under C-arm
      guidance. Signalment, history of trauma, clinical examination, and
      hematobiochemical findings were recorded at the time of presentation. Radiography
      of the affected limb was carried out in two views to determine type and site of
      the fracture. Treatment of all the fractures was attempted using simple Steinman
      and end threaded pinning under the C-arm guidance. The success and failure of the
      closed technique were correlated with age, site, and type of fractures. RESULTS:
      The mean body weight and age of the dogs were 18.53+/-2.18 kg and 21.58+/-5.85
      months, respectively. Early presented cases at a mean day of 2.84+/-0.54 were
      included. Out of 19 cases, it was possible to place implant successfully in 10
      cases (success rate 52.63%) only. The remaining 9 cases had serious
      intraoperative complications like a misdirection of the pin after engaging the
      proximal fragment (n=3), missing the proximal fragment completely, and formation
      of the false tract (n=6). The majority of these complications were associated
      with younger age and proximal or distal third oblique fractures. High success
      rate of C-arm guided closed pinning was observed in midshaft fractures (75%) and
      transverse fractures (77.78%) in dogs of more than 1 year of age (77.78%). Simple
      Steinmann pinning was better feasible in a closed manner with a high success rate
      (66.70%) but also had implant related complications. Although, C-arm guided end
      threaded pinning was less (46.15%) successful, slightly tedious and time
      consuming but had better implant stability than that of simple intramedullary
      pinning. CONCLUSIONS: From the present study, it was concluded that C-arm guided
      closed pinning is recommended in transverse and midshaft fractures of the long
      bones in dogs older than 1 year of age. Furthermore, there is need to improve
      traction devices for enhancing the success of C-arm guided intramedullary pinning
      in dogs.

PMID- 27047054
TI  - Seroepidemiology of infectious bovine rhinotracheitis infection in unvaccinated
      cattle.
AB  - AIM: The present study aimed to investigate the seroepidemiology of infectious
      bovine rhinotracheitis (IBR) infection in the non-vaccinated cattle population in
      northern part of Tamil Nadu, India. MATERIALS AND METHODS: A total of 255 sera
      samples were collected from cattle having the history of respiratory and
      reproductive disorder from cattle of different age, breeds, and sex. All the sera
      samples were subjected to indirect ELISA for the diagnosis of IBR antibodies.
      RESULTS: Results revealed that the seroprevalence of IBR infection among non
      vaccinated cattle population was of 65.88%. No significant difference was noticed
      in the prevalence of IBR infection between cattle showing respiratory (63.64%)
      and reproductive form (70.89%) (p>=0.05). A higher prevalence was noticed in
      animals above 3 years of age (59.60%) and in crossbred animals (71.26%) than
      young and non-descript animals. This study showed the higher prevalence of IBR
      infection in female (67.92%) than in male (33.33%). CONCLUSION: Cattle population
      in this part can better be protected with vaccination than leaving them
      unvaccinated and sero-monitoring shall have to be stressed with regular attempts
      to isolate and characterize the causative agent for IBR.

PMID- 27047055
TI  - Molecular identification of Campylobacter jejuni and coli from chicken, calves
      and dogs to determine its potential threat on human being.
AB  - AIM: Campylobacter is an emerging zoonotic pathogen and one of the leading cause
      of foodborne infection worldwide and it has been isolated from a variety of
      animal species. The aim of this study was to identify Campylobacter jejuni and
      Campylobacter coli from dogs, calves, and poultry using polymerase chain reaction
      (PCR). METHODOLOGY: A total of 104 number of samples comprising cloacal swab from
      poultry (38), a rectal swab from dogs (40), and calves (26) were collected for
      the isolation of thermophilic Campylobacters using conventional culture method.
      PCR was used for identification of mapA gene for C.jejuni and ceuE for C.coli.
      RESULTS: The overall presence of Campylobacter was found to be 67(64.42%) from
      the samples, out of which 6 isolates belongs to C. jejuni species, were 5(18.51%)
      from chicken and 1(4.17%) from dog was recorded and about 17 isolates belongs to
      C. coli species were 9(33.33%), 6 (25%), and 1(9.09%) from chicken, dog and
      calves was recorded. CONCLUSION: Results suggested that Campylobacter reservoirs
      chicken, calves and pet dogs can play a role as the source of infection to human
      beings and PCR can be an ideal tool for molecular confirmation at the species
      level.

PMID- 27047056
TI  - Dominant viral pathologies in the extensive and semi-intensive animal breeding
      and their treatment mode in ethno veterinary medicine in Benin.
AB  - AIM: This study aims to identify the dominant viral animal pathologies and to
      list the traditional recipes used by the breeders for their treatment. MATERIALS
      AND METHODS: The method of data collection was based on a retrospective survey.
      Thus, 787 breeders and agro-breeders scattered in the eight agro-ecological areas
      of Benin were interviewed using semi-structured questionnaires. RESULTS: In
      total, 5 pathologies were reported by breeders. Among those pathologies, foot and
      mouth disease was reported by all of the breeders of the southern part of Borgou
      compared with the other areas (p<0.05) and treated by 25 species of medicinal
      plants. African swine fever was the main pathology reported (22.92%) (p<0.05) in
      the fishery areas which is controlled by 7 medicinal plants. Pseudorinderpest was
      more reported (33.78%) (p<0.05) in the cotton area of central Benin and treated
      by 8 medicinal plants. There is also Newcastle disease that was mostly reported
      in the Western Atacora and treated by 32 medicinal plants as well as fowl pox
      which was a more reported in the lands of the bar area and the low-pressure area
      about 34.48% and 36.17% proportions, respectively, and treated by eight medicinal
      plants. CONCLUSION: The breeders in Benin possess rich ethno veterinary knowledge
      on medicinal plants and their uses in the treatment of livestock. A total of 57
      medicinal plants have been inventoried to fight against five major viral diseases
      as African swine fever, pseudorinderpest and foot and mouth disease. The common
      plants used to treat viral disease in general were Euphorbia unispina, Euphorbia
      poissonii, Lannea acida, and Mangifera indica. The most harvested organs on the
      plants reported in this survey were the barks, the leaves, and the whole plants.
      To better develop our indigenous resources, it would be important to expand this
      ethno-pharmacological investigation to other diseases category.

PMID- 27047057
TI  - Single nucleotide polymorphism mining and nucleotide sequence analysis of Mx1
      gene in exonic regions of Japanese quail.
AB  - AIM: An attempt has been made to study the Myxovirus resistant (Mx1) gene
      polymorphism in Japanese quail. MATERIALS AND METHODS: In the present,
      investigation four fragments viz. Fragment I of 185 bp (Exon 3 region), Fragment
      II of 148 bp (Exon 5 region), Fragment III of 161 bp (Exon 7 region), and
      Fragment IV of 176 bp (Exon 13 region) of Mx1 gene were amplified and screened
      for polymorphism by polymerase chain reaction-single-strand conformation
      polymorphism technique in 170 Japanese quail birds. RESULTS: Out of the four
      fragments, one fragment (Fragment II) was found to be polymorphic. Remaining
      three fragments (Fragment I, III, and IV) were found to be monomorphic which was
      confirmed by custom sequencing. Overall nucleotide sequence analysis of Mx1 gene
      of Japanese quail showed 100% homology with common quail and more than 80%
      homology with reported sequence of chicken breeds. CONCLUSION: The Mx1 gene is
      mostly conserved in Japanese quail. There is an urgent need of comprehensive
      analysis of other regions of Mx1 gene along with its possible association with
      the traits of economic importance in Japanese quail.

PMID- 27047058
TI  - Effect of microclimate alteration on milk production and composition in Murrah
      buffaloes.
AB  - AIM: The aim of this study was to assess the effect of microclimate alteration on
      temperature-humidity index (THI), milk yield, and milk composition of Murrah
      buffaloes during summer for a period of 90-day from March to May-2014 at Buffalo
      Research Station, Venkataramannagudem, Andhra Pradesh, India. MATERIALS AND
      METHODS: A total of 40 lactating Murrah buffaloes were selected having similar
      body weight, parity, and milk yield. They were divided into four groups of 10
      each. Three groups of buffaloes were provided with microclimate alteration using
      supplemental cooling like foggers, fans and foggers plus fans, and the fourth
      group (control) was without any cooling system. The daily THI was measured using
      dry and wet bulb thermometer. The physiological responses viz. rectal
      temperature, respiration rate, and pulse rate were measured by a clinical
      thermometer, measuring the flank movements a minute and observing the pulsation
      of the middle coccygeal artery at the base of tail with the help of finger. Milk
      samples were analyzed for chemical composition viz., fat, solids-not-fat (SNF),
      total solids (TS), specific gravity. RESULTS: In the present study, significant
      (p<0.001) decrease in the average THI values were observed in experimental Murrah
      buffalo houses of GroupII (foggers), GroupIII (fans), and GroupIV (foggers and
      fans) compared to GroupI (control). Significant (p<0.001) decrease in average
      rectal temperature ( degrees F), respiration rate (breaths/min) and pulse rate
      (beats/min) values were recorded in Murrah buffaloes of Groups II, III and IV
      compared to Group I. Significant (p<0.001) increase in the average milk yield
      (kg/day) was recorded in Murrah buffaloes of Groups II, III, and IV compared with
      Group I. Significant (p<0.001) increase in the average milk fat, SNF, and TS
      percent were recorded in Murrah buffalo Groups of II, III, and IV compared with
      Group I. CONCLUSION: Microclimate alteration by the provision of foggers and air
      circulators in the buffalo houses increased feed intake in buffaloes resulting
      increased milk production, fat and SNF yield which was due to decreased heat
      stress in buffaloes.

PMID- 27047059
TI  - Principal component analysis of biometric traits to reveal body confirmation in
      local hill cattle of Himalayan state of Himachal Pradesh, India.
AB  - AIM: In the present study, biometric traits (body length [BL], heart girth [HG],
      paunch girth (PG), forelimb length (FLL), hind limb length (HLL), face length,
      forehead width, forehead length, height at hump, hump length (HL), hook to hook
      distance, pin to pin distance, tail length (TL), TL up to switch, horn length,
      horn circumference, and ear length were studied in 218 adult hill cattle of
      Himachal Pradesh for phenotypic characterization. MATERIALS AND METHODS:
      Morphological and biometrical observations were recorded on 218 hill cattle
      randomly selected from different districts within the breeding tract.
      Multivariate statistics and principal component analysis are used to account for
      the maximum portion of variation present in the original set of variables with a
      minimum number of composite variables through Statistical software, SAS 9.2.
      RESULT: Five components were extracted which accounted for 65.9% of variance. The
      first component explained general body confirmation and explained 34.7%
      variation. It was represented by significant loading for BL, HG, PG, FLL, and
      HLL. Communality estimate ranged from 0.41 (HL) to 0.88 (TL). Second, third,
      fourth, and fifth component had a high loading for tail characteristics, horn
      characteristics, facial biometrics, and rear body, respectively. CONCLUSION: The
      result of component analysis of biometric traits suggested that indigenous hill
      cattle of Himachal Pradesh are small and compact size cattle with a medium hump,
      horizontally placed short ears, and a long tail. The study also revealed that
      factors extracted from the present investigation could be used in breeding
      programs with sufficient reduction in the number of biometric traits to be
      recorded to explain the body confirmation.

PMID- 27047061
TI  - Comparison of immunochromatographic diagnostic test with Hheminested Reverse
      transcriptase polymerase chain reaction for detection of rabies virus from brain
      samples of various species.
AB  - AIM: Detection of rabies is a cause of serious concern in developing countries,
      where dearth of highly equipped laboratories and trained personnel to handle
      sophisticated investigations is felt. The availability of a diagnostic kit, which
      can be used in the field, is essential for diagnosis and control programs as well
      as for epidemiological surveillance of the prevalence of the disease. This study
      was planned to evaluate anigen rabies Ag test kit for its efficacy to be used for
      rapid diagnosis of rabies under field conditions. The test results were compared
      with hemi-nested reverse transcriptase polymerase chain reaction and with a gold
      standard fluorescent antibody test. MATERIALS AND METHODS: A total of 34 brain
      samples from different rabies suspected animals including dogs, buffaloes, cow,
      horse, and cat were examined in this study. RESULTS: Sensitivity of the kit was
      found to be 91.66%, specificity 100%, and accuracy was 94.11%. CONCLUSION: The
      study implies that the immunochromatographic diagnostic test kit may be employed
      for diagnosis of rabies in field conditions.

PMID- 27047060
TI  - Can Urtica dioica supplementation attenuate mercury intoxication in Wistar rats?
AB  - AIM: The objective of this study was to investigate the possible protective role
      of nettle Urtica dioica (UD) against Hg-induced toxicity. MATERIALS AND METHODS:
      A total of 28 rats were equally divided into four groups: the control, the Hg
      (0.8 g HgCl2/kg in the diet), the UD (1.5 ml UD/rat by gavage), and the Hg+UD
      group. HgCl2 was daily dissolved in distilled water and immediately mixed with
      the standard diet. A solution of daily infused fresh nettle leaves in boiling
      water (16 g in 25 ml) was obtained and then it was administrated by gavage.
      Biochemical and reproductive markers, in addition to glutathione (GSH) level
      (liver, kidney and testis) and the histological profiles (testis and epididymis)
      were evaluated after 1 month exposure. RESULTS: Compared to the control, the
      levels of glucose, triglycerides, urea, creatinine, alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were
      significantly raised in the Hg group. In the latter group, the concentrations of
      Mg, Fe, and Ca were significantly decreased. Besides, Hg+UD group has only showed
      raised AST activity and reduced Mg level. Concerning the fertility markers, Hg
      has provoked a significant decrease in the spermatozoa's concentration and
      motility and in plasma testosterone level as well. Furthermore, hepatic, renal
      and testicular GSH concentrations have declined significantly in the Hg treated
      rat compared to the control. A remarkable enhancement of the GSH level was
      observed in all organs of the UD group. The histological examinations of the Hg
      group have revealed marked testicular degeneration of the most seminiferous
      tubules, and showed few sperms in the lumen of epididymis ducts. However, the
      Hg+UD rats have demonstrated an improved histological structure with the presence
      of important numbers of sperms in the lumen. In addition, a clear stabilization
      of organized seminiferous tubules and an increased sperms' numbers were noted in
      the UD supplemented rats. CONCLUSION: Nettle leaves have not only played a clear
      protective role during Hg intoxication, but it also enhanced hepatic, renal and
      testicular GSH level of Wistar rats.

PMID- 27047062
TI  - Effect of feeding varying levels of groundnut haulms on feed intake and growth
      performance in broiler chickens.
AB  - AIM: This study was carried out to evaluate groundnut haulms (GNH) as alternate
      feed source by its incorporation and assessment in terms of feed intake and
      growth performance in the diets of broilers. MATERIALS AND METHODS: A total of
      240 1-day-old Cobb-400 broiler chicks were randomly assigned to four dietary
      treatments each with three replicates (n=60). Experimental Birds in group T1 were
      fed with conventional feed while birds in T2, T3, T4 were fed containing 2%, 4%,
      and 6% of GNH replacing maize and soyabean on iso-nitrogenous basis. RESULTS:
      Feed intake increases significantly (p>0.05) with increasing level of GNH in the
      diets of experimental birds. Highest feed intake was recorded in T4 (6% GNH),
      followed by T3 (4% GNH) than T2 (2% GNH) and T1 (control). Birds fed GNH gained
      significantly (p<0.05) higher body weight than birds fed the control diet. Birds
      in T4 [6% GNH] gained highest body weight, followed by T3 (4% GNH) than T2 (2%
      GNH) and T1 (control). However, feed conversion ratio (FCR) remained non
      significant for all treatment groups. CONCLUSION: On the basis of the results of
      this study, it is concluded that supplementation of GNH can successfully replace
      costly ingredients like maize and soybean meal in the diets of broiler birds up
      to the level of 6 percent of concentrate mixture without any harmful effects on
      feed intake, growth and FCR.

PMID- 27047063
TI  - Effects of fetal bovine serum and estrus buffalo serum on maturation of buffalo
      (Bubalus bubalis) oocytes in vitro.
AB  - AIM: The aim was to assess the effects of fetal bovine serum (FBS) and estrus
      buffalo serum (EBS) on in vitro maturation rate of oocytes in buffalo. MATERIALS
      AND METHODS: Maturation rate of oocytes was assessed in two maturation media
      supplemented with 20% FBS and EBS. Oocytes maturation rate was evaluated on the
      basis of cumulus cell expansion and extrusion of polar body after 24 h of in
      vitro culture in CO2 incubator. RESULTS: The average percentage of in vitro
      matured oocytes in FBS was 83.80%, and EBS was 77.45%, respectively. The results
      revealed a significant (p<0.05) increase in maturation rate of oocytes in FBS
      than EBS. CONCLUSION: Buffalo oocytes were better in vitro matured in FBS than
      EBS.

PMID- 27047064
TI  - Construction and characterization of recombinant human adenovirus type 5
      expressing foot-and-mouth disease virus capsid proteins of Indian vaccine strain,
      O/IND/R2/75.
AB  - AIM: Generation of recombinant human adenovirus type 5 expressing foot-and-mouth
      disease virus (FMDV) capsid protein genes along with full-length 2B, 3B and
      3C(pro) and its characterization. MATERIALS AND METHODS: FMD viral RNA isolation,
      cDNA synthesis, and polymerase chain reaction were performed to synthesize
      expression cassettes (P1-2AB3BC(wt) and P1-2AB3BC(m)) followed by cloning in
      pShuttle-CMV vector. Chemically competent BJ5183-AD-1 cells were transformed with
      the recombinant pShuttle-CMV to produce recombinant adenoviral plasmids. HEK-293
      cells were transfected with the recombinant adenoviral plasmids to generate
      recombinant adenoviruses (hAd5/P1-2AB3BC(wt) and hAd5/P1-2AB3BC(m)). Expression
      of the target proteins was analyzed by sandwich ELISA and indirect
      immunofluorescence assay. The recombinant adenoviruses were purified and
      concentrated by CsCl density gradient ultracentrifugation. Growth kinetics and
      thermostability of the recombinant adenoviruses were compared with that of non
      recombinant replication-defective adenovirus (dAd5). RESULTS: The recombinant
      adenoviruses containing capsid protein genes of the FMDV O/IND/R2/75 were
      generated and amplified in HEK-293 cells. The titer of the recombinant
      adenoviruses was approximately 10(8), 10(9.5) and 10(11) TCID50/ml in supernatant
      media, cell lysate and CsCl purified preparation, respectively. Expression of the
      FMDV capsid protein was detectable in sandwich ELISA and confirmed by
      immunofluorescence assay. Growth kinetics of the recombinant adenoviruses did not
      reveal a significant difference when compared with that of dAd5. A decrement of
      up to 10-fold at 4 degrees C and 21-fold at 37 degrees C was recorded in the
      virus titers during 60 h incubation period and found to be statistically
      significant (p<0.01). CONCLUSION: Recombinant adenoviruses expressing capsid
      proteins of the FMDV O/IND/R2/75 were constructed and produced in high titers. In
      vitro expression of the target proteins in the adenovirus vector system was
      detected by sandwich ELISA and immunofluorescence assay.

PMID- 27047065
TI  - Fungal biological control agents for integrated management of Culicoides spp.
      (Diptera: Ceratopogonidae) of livestock.
AB  - AIM: Entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana had
      wide host range against insects and hence these are being exploited as fungal bio
      pesticide on a large scale. Both fungi are proved pesticides against many crop
      pests and farmers are well acquainted with their use on the field. Thus, research
      was aimed to explore the potency of these fungal spores against larval and adult
      Culicoides midges, a pest of livestock. MATERIALS AND METHODS: In-vitro testing
      of both fungal biological control agents was undertaken in Petri dishes against
      field collected Culicoides larvae, while in plastic beakers against field
      collected blood-engorged female Culicoides midges. In-vivo testing was undertaken
      by spraying requisite concentration of fungal spores on the drainage channel
      against larvae and resting sites of adult Culicoides midges in the cattle shed.
      Lethal concentration 50 (LC50) values and regression equations were drawn by
      following probit analysis using SPSS statistical computerized program. RESULTS:
      The results of this study revealed LC50 values of 2692 mg and 3837 mg (10(8)
      cfu/g) for B. bassiana and M. anisopliae, respectively, against Culicoides spp.
      larvae. Death of Culicoides larvae due to B. bassiana showed greenish coloration
      in the middle of the body with head and tail showed intense blackish changes,
      while infection of M. anisopliae resulted in death of Culicoides larvae with
      greenish and blackish coloration of body along with total destruction, followed
      by desquamation of intestinal channel. The death of adult Culicoides midges were
      caused by both the fungi and after death growth of fungus were very well observed
      on the dead cadavers proving the efficacy of the fungus. CONCLUSION: Preliminary
      trials with both funguses (M. anisopliae, B. bassiana) showed encouraging results
      against larvae and adults of Culicoides spp. Hence, it was ascertained that,
      these two fungal molecules can form a part of biological control and alternative
      to chemical control and, therefore, can be inducted in integrated management
      programs.

PMID- 27047066
TI  - Influence of selenomethionine and omega-3 fatty acid on serum mineral profile and
      nutrient utilization of broiler chicken.
AB  - AIM: This study was conducted to investigate the effect of selenomethionine and
      omega-3 fatty acid on serum mineral profile and nutrient utilization of broiler
      chicken. MATERIALS AND METHODS: The present study was a 2*3 factorial arrangement
      of two levels of selenomethionine (0 and 0.3 ppm) and three levels of omega-3
      fatty acid (0, 0.5 and 1%). Day-old Vencobb broiler chicks (n=180), were randomly
      assigned in six treatment groups. The experiment lasted for 42 days. Treatment
      groups followed of: Group I was a control. Group II, III, IV, V and VI were
      supplemented with 0 ppm selenomethionine with 0.5% omega-3 fatty acid, 0 ppm
      selenomethionine with 1% omega-3 fatty acid, 0.3 ppm selenomethionine with 0%
      omega-3 fatty acid, 0.3 ppm selenomethionine with 0.5% omega-3 fatty acid and 0.3
      ppm selenomethionine with 1% omega-3 fatty acid, respectively. Linseed oil was
      used as a source of omega-3 fatty acid while sel-plex is used for
      selenomethionine supplementation. RESULTS: Significant (p<0.05) interaction exist
      between selenomethionine and omega-3 fatty acid for serum zinc and iron
      concentration whereas, it was non-significant for serum calcium and copper.
      Significantly (p<0.05) increased concentration of selenium, zinc, iron and
      phosphorus was observed in birds fed 0.3 ppm selenomethionine whereas,
      significantly (p<0.05) increased zinc and iron was observed in birds fed 0.5%
      omega-3 fatty acid. There was significant (p<0.05) interaction exist between
      selenomethionine and omega-3 fatty acid for calcium and phosphorus retention
      percentage. The maximum retention of calcium and phosphorus was recorded in birds
      supplemented with 0.3 ppm selenomethionine in combination with 0.5% omega-3 fatty
      acid. There was marked interaction between selenomethionine and omega-3 fatty
      acid for hemoglobin (Hb), total erythrocytic count, total leukocytic count and
      platelets (p<0.05) however, it was non-significant for mean corpuscular volume,
      mean corpuscular Hb, MCH concentration and differential leukocyte count. Dietary
      selenomethionine significantly (p<0.05) increased the platelet count. Hb
      concentration was significantly (p<0.05) higher in birds fed 0.5% omega-3 fatty
      acid whereas, 1% omega-3 fatty acid in the diet drastically increased (p<0.05)
      the platelet count. CONCLUSION: Supplementation of selenomethionine and omega-3
      fatty acid improves the nutrient utilization and mineral retention, which
      subsequently enhance the bone mineralization. Supplementation also helps in
      combating the stress.

PMID- 27047067
TI  - Isolation and in vitro selection of actinomycetes strains as potential probiotics
      for aquaculture.
AB  - AIM: This study was designed to describe a series of in vitro tests that may aid
      the discovery of probiotic strains from actinomycetes. MATERIALS AND METHODS:
      Actinomycetes were isolated from marine sediments using four different isolation
      media, followed by antimicrobial activity and toxicity assessment by the agar
      diffusion method and the hemolysis of human blood cells, respectively.
      Extracellular enzymatic production was monitored by the hydrolysis of proteins,
      lipids and carbohydrates. Tolerance to different pH values and salt
      concentrations was also determined, followed by hydrophobicity analysis and
      genetic identification of the most promising strains. RESULTS: Five out of 31
      isolated strains showed antimicrobial activity against three Vibrio species.
      Three non-hemolytic strains (N7, RL8 and V4) among these active isolates yielded
      positive results in hydrophobicity tests and exhibited good growth at salt
      concentrations ranging from 0% to 10%, except strain RL8, which required a salt
      concentration >0.6%. Although these strains did not grow at pH<3, they showed
      different enzymatic activities. Phylogenetic analysis revealed that strains N7
      and V4 have more than 99% identity with several Streptomyces species, whereas the
      closest matches to strain RL8 are Streptomyces panacagri and Streptomyces
      flocculus, with 98% and 98.2% similarity, respectively. CONCLUSION: Three
      actinomycetes strains showing probiotic-like properties were discovered using
      several in vitro tests that can be easily implemented in different institutions
      around the world.

PMID- 27047068
TI  - Evaluation of egg production after adoption of biosecurity strategies by backyard
      poultry farmers in West Bengal.
AB  - AIM: On the basis of identified source of major bacterial infections at four agro
      climatic zones in West Bengal the cost-effective biosecurity strategy was
      formulated for backyard poultry farmers. The aim of the present study was to
      assess the adoption. So, the study was aimed to detect the adoption level of the
      formulated biosecurity strategy to mitigate the Salmonella and Escherichia
      coliweek post-hatch period chicks were contamination level in the sources and its
      correlation with egg production in West Bengal. MATERIALS AND METHODS: A
      questionnaire was prepared querying regarding the biosecurity measures presently
      followed by the farmers, if any and egg production of their birds. Subsequent to
      the interview the formulated biosecurity strategy was conveyed. After 3 months,
      the interview with the same questionnaire was conducted to the same farmers to
      detect their adoption level. RESULTS: The change in practices were noted in
      certain parameters which differs significantly (p<0.01 or p<0.05). As a
      consequence, the average egg production/flock was increased in 3 months after
      adoption of the strategy (618.2+/-37.77/flock) in comparison to last 3 months
      average before adoption of the strategy (495.3+/-30.00/flock) which also differs
      significantly (p<0.01). CONCLUSION: The present study detected the implementation
      of the biosecurity strategy in backyard poultry farming in West Bengal can
      substantially benefit the farmers in terms of increased egg production.

PMID- 27047069
TI  - Chromosomal profile of indigenous pig (Sus scrofa).
AB  - AIM: The objective of this study was to investigate the chromosomal profile of
      indigenous pigs by computing morphometric measurements. MATERIALS AND METHODS: A
      cytogenetic study was carried out in 60 indigenous pigs to analyze the
      chromosomal profile by employing the short term peripheral blood lymphocyte
      culture technique. RESULTS: The modal chromosome number (2n) in indigenous pigs
      was found to be 38 and a fundamental number of 64 as in the exotic. First
      chromosome was the longest pair, and thirteenth pair was the second largest while
      Y-chromosome was the smallest in the karyotype of the pig. The mean relative
      length, arm ratio, centromeric indices and morphological indices of chromosomes
      varied from 1.99+/-0.01 to 11.23+/-0.09, 1.04+/-0.05 to 2.95+/-0.02, 0.51+/-0.14
      to 0.75+/-0.09 and 2.08+/-0.07 to 8.08+/-0.15%, respectively in indigenous pigs.
      Sex had no significant effect (p>0.05) on all the morphometric measurements
      studied. CONCLUSION: The present study revealed that among autosomes first five
      pairs were sub metacentric, next two pairs were sub telocentric (6-7), subsequent
      five pairs were metacentric (8-12) and remaining six pairs were telocentric (13
      18), while both allosomes were metacentric. The chromosomal number, morphology
      and various morphometric measurements of the chromosomes of the indigenous pigs
      were almost similar to those established breeds reported in the literature.

PMID- 27047070
TI  - Influence of post hatch dietary supplementation of fat on performance, carcass
      cuts and biochemical profile in Ven Cobb broiler.
AB  - AIM: The present experiment was conducted to study the effect of post hatch
      dietary fat supplementation on performance of broiler chicken. MATERIALS AND
      METHODS: A total of 120 day-old Ven Cobb broiler chicks were randomly assigned to
      4 treatment groups of 30 chicks in each (three replicates of 10 birds/treatment).
      The trial lasted for 35 days. The experimental design was a completely randomized
      design. Four types of diet were formulated for 1(st) week: T1, T2, T3 and T4
      contained control diet with no added fat, 2.5, 5 and 7.5% fat, respectively.
      After 1(st) week post-hatch period chicks were fed ad libitum with the normal
      basal diet as per Bureau of Indian Standard recommendations till completion of
      the experiment (8-35 days). RESULTS: Significantly higher (p<0.05) body weight
      and improved feed conversion ratio (FCR) was recorded in birds fed 5% dietary fat
      at the end of the experiment whereas, feed intake was not significantly affected.
      Significantly (p<0.05) higher dressed weight was observed due to 5% fat
      supplementation than other groups whereas, it was not significant for other
      carcass cuts. No significant differences were observed in moisture, protein and
      lipid content of breast and thigh muscle of broiler due to supplemented fat
      whereas, 2.5% dietary fat significantly (p<0.05) increase the serum HI titer on
      day 28(th). In biochemical profile, higher serum albumin (g/dl) was recorded due
      to 5% fat supplementation whereas other biochemical components did not show any
      significance difference among treatments. CONCLUSION: It may be concluded that
      supplementation of fat in broilers diet improves the overall FCR, dressing
      percentage and gain more body weight.

PMID- 27047071
TI  - Disposal rate in different age groups of Karan Fries (Crossbred) males in
      organized herd.
AB  - AIM: The present study was carried out to analyze the disposal rate in different
      age groups of Karan Fries (KF) males in National Dairy Research Institute herd.
      MATERIALS AND METHODS: Records on 1740 KF crossbred bulls born during the period
      1997-2012 were collected with an objective to ascertain the effect of genetic and
      non-genetic (Period of birth and season of birth) factors on the disposal pattern
      of KF males. The percent of animals disposed from the herd due to mortality and
      culling was calculated by proportion using descriptive statistics. The data were
      subjected to Chi-square test to test the difference due to different factors.
      RESULTS: Overall disposal rate for the different age groups of 0-1 m, 1-2 m, 2-3
      m, 3-6 m, 6-18 m, 18 m-3 year and 3-5 year were calculated as 17.9, 16.3, 14.2,
      25.8, 49.0, 37.6 and 51.65%, respectively. In the age groups, 3-6 m, 6-18 m and 3
      5 year, effect of periods of birth were found to be statistically significant
      (p<0.01) for overall disposal rate. Across different seasons of birth, overall
      disposal rates differed significantly (p<0.01) in different age group except in 3
      5 year age group. Differences in overall disposal rate due to genetic group were
      statistically significant (p<0.01) in 1-2 m, 2-3 m, 3-6 m, 6-18 m, 18-3 year and
      3-5 year age groups. CONCLUSION: Overview of the results indicated that higher
      overall disposal rate in age group of 1 month was due to mortality while, in the
      age groups of >1 month, culling was the primary cause.

PMID- 27047072
TI  - Fractionation of carbohydrate and protein content of some forage feeds of
      ruminants for nutritive evaluation.
AB  - AIM: To evaluate some forage feeds of ruminants in terms of their carbohydrate
      (CHO) and protein fractions using Cornell Net Carbohydrate and Protein System
      (CNCPS). MATERIALS AND METHODS: Eleven ruminant feeds (six green fodders - maize,
      oat, sorghum, bajra, cowpea, berseem and five range herbages - para grass, guinea
      grass, hedge lucerne, setaria grass and hybrid napier) were selected for this
      study. Each feed was chemically analyzed for proximate principles (dry matter,
      crude protein [CP], ether extract, organic matter and ash), fiber fractions
      (neutral detergent fiber, acid detergent fiber, acid detergent lignin, cellulose
      and hemicellulose), primary CHO fractions (CHO, non-structural CHO, structural
      CHO and starch) and primary protein fractions (neutral detergent insoluble CP,
      acid detergent insoluble CP, non-protein nitrogen and soluble protein). The
      results were fitted to the equations of CNCPS to arrive at various CHO (CA - fast
      degrading, CB1 - intermediate degrading, CB2 - slow degrading and CC - non
      degrading or unavailable) and protein (PA - instantaneously degrading, PB1 - fast
      degrading, PB2 - intermediate degrading, PB3 - slow degrading and PC - non
      degrading or unavailable) fractions of test feeds. RESULTS: Among green fodders,
      cowpea and berseem had higher CA content while except hedge lucerne all range
      herbages had lower CA values. CB1 content of all feeds was low but similar. All
      feeds except cowpea, berseem, and hedge lucerne contained higher CB2 values. Oat
      among green fodders and hybrid napier among range herbages had lower CC fraction.
      Feeds such as bajra, cowpea, berseem and the setaria grass contained lower PA
      fraction. All green fodders had higher PB1 content except maize and cowpea while
      all range herbages had lower PB1 values except hedge lucerne. Para grass and
      hybrid napier contained exceptionally low PB2 fraction among all feeds. Low PC
      contents were reported in oat and berseem fodders. CONCLUSION: Based on our
      findings, it was concluded that feeds with similar CP and CHO content varied
      significantly with respect to their CHO and protein fractions. Due to lower CC
      fraction, oat and hybrid napier were superior feeds in terms of CHO supply to
      ruminants. Similarly, among all feeds oat and berseem had a lower PC fraction,
      thus were considered good sources of protein for ruminants.

PMID- 27047073
TI  - Rumen modulatory effect of thyme, clove and peppermint oils in vitro using
      buffalo rumen liquor.
AB  - AIM: The present study was conducted to examine the rumen modulatory effect of
      thyme, clove and peppermint oils on rumen fermentation pattern in vitro using
      roughage based diet. MATERIALS AND METHODS: Thyme, clove and peppermint oils were
      tested at concentration of 0, 30, 300 and 600 mg/l (ppm) of total culture fluid
      using in vitro gas production technique in wheat straw based diet (concentrate:
      Wheat straw 50:50). Different in vitro parameters e.g., total gas production,
      methane production, nutrient degradability, volatile fatty acid (VFA) production
      and ammonia nitrogen concentration were studied using buffalo rumen liquor.
      RESULTS: Thyme oil at higher dose level (600 ppm) reduced (p<0.05) total gas
      production, feed degradability and ammonia nitrogen (NH3-N) concentration whereas
      total VFA concentration was significantly lower (p>0.05) in 300 and 600 ppm dose
      levels. 600 ppm dose level of clove oil reduced (p<0.05) total gas production,
      feed degradability, total VFA and acetate to propionate ratio. Methane production
      was significantly reduced (p<0.05) in 300 and 600 ppm dose levels of clove and
      peppermint oil. CONCLUSION: Right combination of these essential oils may prove
      to enhance performance of animals by reducing methane production and inhibiting
      protein degradation in rumen.

PMID- 27047074
TI  - Ultrasonographic assessment of the equine palmar tendons.
AB  - AIM: The present study was conducted to evaluate the equine palmar tendon by
      ultrasonography (USG) in standing the position. MATERIALS AND METHODS: USG of
      palmar tendons was performed in 40 adult horses using linear transducer having
      frequency of 10-18 MHz (e-soate, My Lab FIVE) and L52 linear array transducer
      (Titan, SonoSite) with frequencies ranging from 8 to 10 MHz. Palmar tendon was
      divided into 7 levels from distal to accessory carpal bone up to ergot in
      transverse scanning and 3 levels in longitudinal scanning. RESULTS: The USG
      evaluation was very useful for diagnosis of affections of the conditions such as
      chronic bowed tendon, suspensory ligament desmitis, carpal sheath tenosynovitis
      and digital sheath effusions. The mean cross-sectional area (cm(2)) of affected
      tendons was significantly increased in affected than normal tendons. The
      echogenicity was also found reduced in affected tendons and ligaments along with
      disorganization of fiber alignment depending on the severity of lesion and
      injury. CONCLUSION: USG proved ideal diagnostic tool for diagnosis and post
      treatment healing assessment of tendon injuries in horses.

PMID- 27047075
TI  - Effects of beta-mercaptoethanol on in vitro maturation and glutathione level of
      buffalo oocytes.
AB  - AIM: The present study was carried out to evaluate the effect of supplementation
      of beta-mercaptoethanol (beta-ME) on in vitro maturation rate and glutathione
      (GSH) level of buffalo oocytes. MATERIALS AND METHODS: Oocytes were recovered
      from buffalo's ovaries collected from government approved slaughter house (near
      Kamela darwaza, Surat) of Surat Municipal Corporation. The obtained oocytes were
      in vitro matured in maturation media supplemented with 0 MUM (117 oocytes), 100
      MUM (46 oocytes) and 200 MUM (42 oocytes) concentration of beta-ME. After 24 h of
      incubation, maturation rate of oocytes and intra-cellular GSH level were
      determined. RESULTS: The results showed that the presence of beta-ME did not
      influence (p>0.05) the oocyte maturation rate. However, GSH level increased
      significantly (p<0.05) in matured oocytes when supplemented with 100 MUM and 200
      MUM beta-ME (6.19+/-0.10 and 6.37+/-0.20 pmol/oocyte) as compared to control
      media (4.68+/-0.26 pmol/oocyte). CONCLUSION: It was concluded that beta-ME may
      have a potential to increase the meiotic maturation of in vitro cultured oocytes
      and protect it from oxidative damage.

PMID- 27047077
TI  - Studies on incidence and evaluation of the closed medial patellar desmotomy in
      lateral recumbency in bovines.
AB  - AIM: The present study was conducted to find out the incidence and to evaluate
      the effectiveness of medial patellar desmotomy (MPD) in lateral recumbency in
      bovines. MATERIAL AND METHODS: One hundred and fifteen clinical cases of upward
      fixation of the patella in cattle and buffaloes were treated by closed MPD in
      lateral recumbency. Probable etiologies, symptoms and site of surgery including
      disease occurrence with respect to species, sex and season were also recorded.
      RESULTS: In the present study, the highest incidence was reported in bullocks. A
      high success rate was obtained with the closed method in lateral recumbency.
      CONCLUSION: Based on the findings of this study, it can be concluded that the
      bullocks were more prone to upward fixation of patella and symptoms were
      exaggerated in winter season. Closed method of MPD was more suited in both cattle
      and buffaloes.

PMID- 27047076
TI  - Seroprevalence of Brucella abortus and Leptospira hardjo in cattle.
AB  - AIM: The aim was to assess the seroprevalence of B. abortus and Leptospira hardjo
      in the cattle population of Bihar, this work was carried out. MATERIALS AND
      METHODS: Randomly selected 450 cattle from nine districts of Bihar were
      serologically screened for antibodies against L. hardjo and B. abortus. DAS-ELISA
      for leptospira and AB-ELISA for brucella were carried out. Based on the results
      prevalence in each district and the state are reported herewith. RESULTS AND
      DISCUSSION: In this study, it was found that the seroprevalence of L. hardjo was
      9.11% and that of B. abortus was 12.2% in Bihar. Indigenous cattle were found to
      be less susceptible to leptospirosis and brucellosis even though they accounted
      for 83.11% of the study population. CONCLUSION: Although there was no acute
      disease, antibodies detected against L. hardjo and B. abortus in the cattle
      population indicated the presence of chronic and subclinical infection, which
      could challenge the fertility of the animals.

PMID- 27047078
TI  - Study on inclusion of probiotic, prebiotic and its combination in broiler diet
      and their effect on carcass characteristics and economics of commercial broilers.
AB  - BACKGROUND AND AIM: In today era, broiler industry facing a problem of price
      hiking of feed of broiler, also in competitive era there should be lower feed
      cost, lower feed conversion ratio, low feed consumption yet good body weight at
      marketable age. MATERIALS AND METHODS: Day-old commercial broiler chicks (n=200)
      were distributed randomly into 5 dietary treatment groups viz. control (T1),
      probiotic in the feed @ 100 g/tonne of feed (T2), prebiotic in the feed @ 500
      g/tonne of feed (T3), probiotic + prebiotic @ 100 g/tonne and 500 g/tonne of
      feed, respectively (T4) and probiotic + prebiotic @ 50 g/tonne and 250 g/tonne of
      feed (T5). The growth of broilers and dressing weight along with the weight of
      giblet (liver without gall bladder, gizzard without serous layer, and heart
      without pericardium), Kidney, Abdominal fat, Length of Intestine and dressing
      percentage were measured. Economics in terms of Return Over Feed Cost (ROFC) and
      European Performance Efficiency Index (EPEI) was calculated. RESULTS: Among all
      carcass traits, dressing percentage, abdominal fat weight and abdominal fat
      percentage (as a percentage of dressed weight) were recorded significant (p<0.05)
      difference among different treatment groups. The income from selling of the birds
      was significantly (p<0.05) higher in all treatment groups than the control group
      but there was a non-significant difference between supplemented groups. Feed cost
      during whole experimental period was significantly (p<0.05) lower in synbiotic
      supplemented groups (T4 and T5) than other groups. ROFC of all treatment group
      found significantly (p<0.05) higher than the control group. CONCLUSION: It can be
      concluded that the diet supplemented with synbiotic (100% level) was most
      efficient in terms of EPEI and synbiotic (50% level) in terms of ROFC. Hence, as
      feed supplement, synbiotic has a beneficial effect over probiotic and prebiotic
      when used alone.

PMID- 27047079
TI  - Egg shell and yolk quality characteristics of layers fed with sugarcane press
      residue in soya and fish based diets.
AB  - AIM: Sugarcane press residue (SPR), a by-product of sugarcane industry, which is
      rich in inorganic salts was assessed at different levels in both soya based and
      fish based diets of layers for egg shell and yolk quality characteristics.
      MATERIALS AND METHODS: SPR was incorporated in 32-week-old white leghorn layer
      diets at 0%, 5%, 10% and 15% either in the soya based or fish based diets to form
      T1 to T8 diets, respectively. Each diet was offered to five replicates of four
      laying hens each constituting a total of one sixty birds kept for 84 days under
      colony cages. RESULTS: Mean egg shell thickness obtained from eggs of
      experimental hens measured was 0.342, 0.329, 0.320, 0.322, 0.319, 0.332, 0.328
      and 0.336 mm in T1 through T8 groups, respectively. About the main factor
      effects, both showed non-significant results. Similarly, influence of different
      treatment diets, in imparting colour to the yolks, was found to be non
      significant (p>0.05) at different 28-day time intervals. Further, the average
      yolk index values ranged non-significantly from 0.360 (T6) to 0.383 (T4).
      CONCLUSION: The SPR can be incorporated into layer diet as a source of inorganic
      as well as organic nutrients without affecting its egg quality characteristics.

PMID- 27047080
TI  - Relative efficacy of egg yolk and soya milk-based extenders for cryopreservation
      (-196 degrees C) of buffalo semen.
AB  - AIM: The aim was to compare commercially available soybean milk-based extenders,
      viz. Bioxcell((r)) and Optixcell((r)) (IMV, France) with standard Tris-citrate
      fructose-egg yolk-glycerol (TFYG) extender for cryopreservation of buffalo semen.
      MATERIALS AND METHODS: Semen was collected twice a week in artificial vagina from
      six sexually mature, 4-6 years old, healthy breeding bulls of Surti buffalo
      breed. In all 48 qualifying ejaculates (8 per bull) having initial motility >70%
      were split into three equal aliquots and were diluted (at 34 degrees C keeping
      100*10(6) sperm ml(-1)) in TFYG, Bioxcell and Optixcell extenders. The French
      mini straws filled from each aliquot were gradually cooled to 4-5 degrees C,
      equilibrated at 4 degrees C for 4 h and frozen in liquid nitrogen 2 vapor using
      programmable biofreezer. Just before freezing (post-equilibration) and 24 h after
      frozen storage, the samples were evaluated for various sperm quality parameters
      using standard protocols. Frozen semen straws were thawed in a water bath at 37
      degrees C for 30 s. The post-thaw incubation survival (37 degrees C for 1 h) was
      assessed through motility rating at 0, 30 and 60 min of incubation. RESULTS: The
      mean percentages of prefreeze sperms in TFYG, Bioxcell and Optixcell extenders in
      terms of progressive motility (69.48+/-0.37, 68.02+/-0.49, 70.94+/-0.38),
      viability (79.21+/-0.39, 77.38+/-0.48, 81.58+/-0.38), total abnormalities (7.90+/
      0.14, 8.60+/-0.16, 7.08+/-0.15), intact acrosome (89.54+/- 0.18, 88.58+/-0.22,
      90.52+/-0.21) and hypoosmotic swelling (HOS) reactivity (67.96+/-0.32, 65.65+/
      0.42, 70.23+/-0.37) varied significantly (p<0.05) between extenders. Similar
      pattern of significant (p<0.05) variations between these extenders for post-thaw
      sperm progressive motility (47.71+/-0.79, 44.38+/-0.85, 49.90+/-0.90), viability
      (57.19+/-0.79, 53.85+/-0.84, 59.67+/-0.91), total abnormalities (12.33+/-0.17,
      12.75+/-0.21, 11.27+/-0.18), intact acrosome (76.83+/-0.23, 75.90+/- 0.27,
      78.50+/-0.25) and HOS reactivity (45.02+/-0.84, 42.31+/-0.82, 47.81+/-0.90) was
      also observed for TFYG, Bioxcell and Optixcell extenders. The recently launched
      improved soybean milk-based extender Optixcell excelled the older Bioxcell
      extender and even standard TFYG in respect of some of the sperm quality
      parameters. CONCLUSION: The advantages of soy lecithin-based bovine semen
      extenders over egg yolk regarding sanitary issues are unquestionable but still
      egg yolk-based semen extenders are widely used because of the cost factor and
      good in vivo fertility results.

PMID- 27047081
TI  - Pock forming ability of fowl pox virus isolated from layer chicken and its
      adaptation in chicken embryo fibroblast cell culture.
AB  - AIM: The objective of the present study was to examine pock forming ability of
      field strain and vaccine strain of fowl pox virus (FPV) in chorioallantoic
      membrane (CAM) of embryonated chicken eggs and its adaptation in chicken embryo
      fibroblast (CEF) cell culture. MATERIALS AND METHODS: Dry scabs were collected
      from 25 affected birds in glycerin-saline and preserved at 4 degrees C until
      processed. Virus was isolated in 10-day-old embryonated chicken eggs by dropped
      CAM method. The identity of the virus is confirmed by clinical findings of
      affected birds, pock morphology and histopathology of infected CAM. In addition
      one field isolate and vaccine strain of FPV was adapted to CEF cell culture. CEF
      cell culture was prepared from 9-day-old embryonated chicken eggs. RESULT:
      Clinical symptoms observed in affected birds include pox lesion on comb, wattle,
      eyelids and legs, no internal lesions were observed. All field isolates produced
      similar findings in CAM. Pocks produced by field isolates ranged from 3 mm to 5
      mm at the third passage while initial passages edematous thickening and necrosis
      of CAM was observed. Pocks formed by lyophilized strain were ranges from 0.5 mm
      to 2.5 mm in diameter scattered all over the membrane at the first passage. Intra
      cytoplasmic inclusion bodies are found on histopathology of CAM. At third passage
      level, the CEF inoculated with FPV showed characteristic cytopathic effect (CPE)
      included aggregation of cells, syncytia and plaque formation. CONCLUSION: FPV
      field isolates and vaccine strain produced distinct pock lesions on CAMs.
      Infected CAM showed intracytoplasmic inclusion bodies. The CEF inoculated with
      FPV field isolate as well as a vaccine strain showed characteristic CPE at third
      passage level.

PMID- 27047082
TI  - Evaluation of efficacy and safety of glycopyrrolate - xylazine - propofol
      anesthesia in buffalo calves.
AB  - AIM: To evaluate the efficacy and safety of glycopyrrolate - xylazine - propofol
      anesthesia in buffalo calves. MATERIALS AND METHODS: The study was conducted on
      six clinically healthy male buffalo calves, 6-12 months of age, and weighing
      between 130 and 170 kg. In all the animals; glycopyrrolate (0.01 mg/kg, IM),
      xylazine (0.1 mg/kg, IM) and 1% propofol as single bolus (1.5 mg/kg,
      intravenous), were administered. The parameters observed included behavioral
      changes, physiological; hematological and blood biochemical parameters. RESULTS:
      Muzzle and nostrils became dry in all the animals after glycopyrrolate
      administration. A decrease in spontaneous activity and mild cutaneous analgesia
      was noticed after xylazine administration. After administration of propofol, loss
      of swallowing reflex, palpebral reflex, corneal reflexes, periosteal reflex and
      complete analgesia was observed. There was no significant change in rectal
      temperature and heart rate. However, heart rate remained elevated during
      anesthesia. Respiratory rate decreased significantly after propofol
      administration. There was a significant increase in plasma glucose after the
      xylazine and propofol administration which remained elevated till recovery. A
      significant decrease in chloride level was seen after propofol administration.
      CONCLUSIONS: Glycopyrrolate - xylazine - propofol anesthetic combination may
      safely be used for short duration anesthesia in buffalo calves.

PMID- 27047084
TI  - Evaluation of geriatric changes in dogs.
AB  - AIM: The present study has been envisaged to ascertain the old age for critical
      management of geriatric dogs considering the parameters of externally visible
      changes, haemato-biochemical alterations and urine analysis in geriatric dogs
      approaching senility. MATERIALS AND METHODS: The study was undertaken in the
      Department of Veterinary Pathology in collaboration with Teaching Veterinary
      Clinic complex spanning a period of 1 year. For screening of geriatric dogs,
      standard geriatric age chart of different breeds was followed. The external
      characteristics such as hair coat texture, dental wear and tear, skin texture and
      glaucoma were taken as a marker of old age. Haematology, serum biochemistry and
      urine analysis were also included in the study. RESULTS: External visible changes
      like greying of hair, dull appearance of hair coat, glaucoma, osteoarthritis,
      dental wear and tear were commonly encountered in the aged dogs. The haemoglobin,
      total erythrocyte count and packed cell volume showed a decreasing trend in the
      geriatric groups. Biochemical values like total protein, albumin, calcium level
      showed a decreasing trend while urea level with an increasing trend in geriatric
      dogs without any much alteration in serum glutamic-oxaloacetic transaminse, serum
      glutamic-pyruvate transaminase, cholesterol and creatinine. Physical examination
      of urine revealed yellow, amber, red, deep red color with turbidity and higher
      specific gravity. Chemical examination revealed presence of protein, glucose,
      ketone bodies, blood and bilirubin on some cases. The culture and sensitivity
      test of the urine samples revealed presence of bacteria with sensitive and
      resistance to some antibiotics. CONCLUSION: External visible changes are still
      the golden standard of determining the old age in dogs. Haemato-biochemical
      evaluation can be useful for correlating with the pathophysiological status of
      the animal. Biochemical analysis of urine can be employed rightly as kidney
      dysfunction is being major geriatric problem. Anaemia, jaundice, nephritis,
      hepatitis are the most common findings considered during old age.

PMID- 27047083
TI  - The commercial impact of pig Salmonella spp. infections in border-free markets
      during an economic recession.
AB  - The genus Salmonella, a group of important zoonotic pathogens, is having global
      economic and political importance. Its main political importance results from the
      pathogenicity of many of its serovars for man. Serovars Salmonella Enteritidis
      and Salmonella Typhimurium are currently the most frequently associated to
      foodborne infections, but they are not the only ones. Animal food products
      contaminated from subclinically infected animals are a risk to consumers. In
      border free markets, an example is the EU, these consumers at risk are
      international. This is why, economic competition could use the risk of consumer
      infection either to restrict or promote free border trade in animals and their
      products. Such use of public health threats increases during economic recessions
      in nations economically weak to effectively enforce surveillance. In free trade
      conditions, those unable to pay the costs of pathogen control are unable to
      effectively implement agreed regulations, centrally decided, but leaving their
      enforcement to individual states. Free trade of animal food products depends
      largely on the promotion of safety, included in "quality," when traders target
      foreign markets. They will overtake eventually the markets of those ineffectively
      implementing agreed safety regulations, if their offered prices are also
      attractive for recession hit consumers. Nations unable to effectively enforce
      safety regulations become disadvantaged partners unequally competing with
      producers of economically robust states when it comes to public health. Thus,
      surveillance and control of pathogens like Salmonella are not only quantitative.
      They are also political issues upon which states base national trade decisions.
      Hence, the quantitative calculation of costs incurring from surveillance and
      control of animal salmonelloses, should not only include the cost for public
      health protection, but also the long term international economic and political
      costs for an individual state. These qualitative and qualitative costs of man and
      animal Salmonella infections should be calculated in the light of free trade and
      open borders. Understandably, accurate calculation of the economic and political
      costs requires knowledge of the many factors influencing nationally the quality
      and safety of pork products and internationally free trade. Thus, how Salmonella
      pig infections affect commerce and public health across open borders depends on a
      state's ability to accurately calculate costs for the surveillance and control of
      animal salmonelloses in general, and pig infections as a particular example. 

PMID- 27047085
TI  - The effect of gabapentin and pregabalin on intestinal incision wound healing in
      rabbits.
AB  - AIM: To evaluate the macroscopic and histologic effects of pregabalin (PG)
      gabapentin (GB) on longitudinal intestinal wound healing in New Zealand rabbits.
      MATERIALS AND METHODS: The animals were divided into three groups randomly; the
      control group (n=6), PG group (n=6) and GB group (n=6). All animals were
      premedicated with xylazine HCI, 5 mg/kg i.m. and general anaesthesia was
      performed by ketamine HCI 50 mg/kg i.m injection. A 4 cm incision in the caecum
      through median laparotomy was achieved under aseptic surgery. Intestinal wound
      was closed with double-sutured. All animals were received parenteral antibiotic
      treatment for 5 days. PG and GB groups were treated by PG (30 mg/kg, oral, daily)
      and GB (30 mg/kg, oral, daily) for 10 days respectively. Control group did not
      receive any treatment. The animals were euthanized on day 10 and the caecum was
      examined by laparotomy. Adhesion formation was observed, and tissue samples were
      taken from suture lines for histologic examination. Cellular infiltration
      (polymorphonuclear white blood cells and mononuclear cells), accumulation of
      connective tissue, vascularization and extent of necrosis were evaluated and
      scored separately for each of mucosal, submucosal, muscular and serosal layers of
      caecum. RESULTS: Adhesions were more severe in the GB group compared to other
      groups. No statistically significant differences were detected among the three
      groups about the wound healing. CONCLUSION: It was suggested that the use of
      gabapentinoids had no significant effect on wound healing in patients undergoing
      gastrointestinal surgery and further studies with treatment periods longer than
      10 days are needed.

PMID- 27047086
TI  - Release of beta-endorphin, adrenocorticotropic hormone and cortisol in response
      to machine milking of dairy cows.
AB  - AIM: The present study was undertaken with the objective to obtain insight into
      the dynamics of the release of beta-endorphin, adrenocorticotrophic hormone
      (ACTH) and cortisol in response to machine milking in dairy cows. MATERIALS AND
      METHODS: A total of 10 healthy multiparous lactating Italian Friesian dairy cows
      were used in the study. Animals were at the 4(th)-5(th) month of pregnancy and
      were submitted to machine milking 2 times daily. Blood samples were collected in
      the morning: In baseline conditions, immediately before milking and after
      milking; and in the early afternoon: In baseline conditions, before milking and
      after milking, for 2 consecutive days. Endocrine variables were measured in
      duplicate, using a commercial radioimmunoassay for circulating beta-endorphin and
      ACTH concentrations and a competitive enzyme-linked immunoassay for cortisol
      concentration. RESULTS: Data obtained showed a similar biphasic cortisol
      secretion of lactating dairy cows, with a significant increase of cortisol
      concentration after morning machine milking, at both the 1(st) and the 2(nd) day
      (p<0.05), and a decrease after afternoon machine milking at the 2(nd) day
      (p<0.01). One-way RM ANOVA showed significant effects of the machine milking on
      the cortisol changes, at both morning (f=22.96; p<0.001) and afternoon (f=15.10;
      p<0.01) milking, respectively. Two-way RM ANOVA showed a significant interaction
      between cortisol changes at the 1(st) and the 2(nd) day (f=7.94; p<0.0002), and
      between the sampling times (f=6.09; p<0.001). Conversely, no significant effects
      of the machine milking were observed on beta-endorphin and ACTH changes, but only
      a moderate positive correlation (r=0.94; p<0.06) after milking stimuli.
      CONCLUSIONS: A wide range of cortisol concentrations reported in this study
      showed the complex dynamic patterns of the homeostatic mechanisms involved during
      machine milking in dairy cows, suggesting that beta-endorphin and ACTH were not
      the main factors that caused the adrenocortical response to milking stimuli.

PMID- 27047087
TI  - Body condition score and its correlation with ultrasonographic back fat thickness
      in transition crossbred cows.
AB  - AIM: The aim was to study the effect of the transition to body condition score
      (BCS) and ultrasonographic back fat thickness (USG BFT) in crossbred cows.
      MATERIALS AND METHODS: A total of 101 multiparous crossbred cows in advanced
      pregnancy from organized dairy farm were taken up for study. The cows were
      grouped according to transition stage, i.e. far off dry (FOD), close up dry (CUD)
      and fresh (F). BCS was estimated by using the five point visual BCS technique
      with 0.5 increments. The USG BFT was measured by real-time ultrasound using a
      portable Sonosite instrument. RESULTS: In cows with BCS 2-2.5, the BFT of F
      period was significantly lower than FOD period. In cows with BCS 3-3.5, the mean
      BFT at F period was significantly reduced as compared to FOD and CUD period. The
      overall correlation coefficient between BCS and BFT for different transition
      stages was 84%, 79% and 75% for FOD, CUD and F period, respectively. CONCLUSION:
      The USG BFT gives an accurate measure of fat reserves in cows. The cows with BCS
      of >=3.5 entering the transition period are more prone to lose body condition and
      hence require better and robust management during the transition period.

PMID- 27047088
TI  - Expression of bovine interleukin 15 and evaluation of its biological activity in
      vitro.
AB  - BACKGROUND/AIM: Recent studies have shown that interleukin-15 (IL-15)is a
      critical factor for the development and proliferation of CD8(+) memory T cells.
      The aim of present study is to study the role bovine IL-15 (bIL-15)in activation
      pathway of bovine CD8(+) T cells if any, which will be useful in designing the
      adjuvant to increase the duration of immunity of the vaccine preparations.
      MATERIALS AND METHODS: Coding region of bIL-15 (489) was amplified from cDNA of
      lipopolysaccharide-induced bovine peripheral blood mononuclear cells (PBMCs)
      using gene specific primers and cloned into pcDNA3.1(+). Mature length of bIL-15
      was amplified using gene specific primers and cloned into pET32a for expression
      studies. Expressed fusion protein was purified using Ni-Nitrilotriacetic acid
      agarose affinity chromatography and analyzed by SDS-Polyacryamide gel
      electrophoresis (PAGE) and western blotting. Biological activity of purified
      protein was analyzed by quantitative Polymerase Chain Reaction (qPCR) for an
      increase in levels of Bcl2, STAT3 and STAT5a using cDNA synthesized from RNA of
      PBMCs induced with different concentrations of purified bIL-15. Role of IL-15 in
      inducing memory CD8(+) T cells was analyzed by qPCR for increase in the level of
      Carnitine Palmitoyl Transferase 1a (CPT1a) using cDNA synthesized from RNA of
      PBMCs induced with different concentrations of purified bIL-15. RESULTS: Bovine
      IL-15 was amplified and analyzed by agarose gel electrophoresis, which showed a
      specific product of ~490bp, mature sequence was amplified using full-length as a
      template to get a product of ~350bp. The protein was expressed, purified and
      analyzed by SDS-PAGE and Western blotting, which showed a specific product of
      32kDa. Biological activity of purified bIL-15 fusion protein showed an increase
      in levels of Bcl2, STAT3 and STAT5a with 5 fold, 9 fold, and 10 fold increases as
      analyzed by qPCR, respectively. Role of IL-15 in inducing memory T cells showed
      an increase in expression level of CPT1a at 2.5 fold increase as compared to
      control cells. CONCLUSION: Bovine IL-15 has been successfully cloned and
      expressed in our work, and the biological activity shows that the purified fusion
      protein is biologically active. As there is an increase in levels of CPT1a an
      enzyme critical for survival of memory T cells, IL-15 can be used for increase in
      the memory response, which can be used as an adjuvant with viral vaccines for
      increasing the immunity.

PMID- 27047090
TI  - Fertility response in postpartum anoestrus buffaloes (Bubalus bubalis) using
      modified Ovsynch based timed insemination protocols.
AB  - BACKGROUND AND AIM: Suboestrus constitutes the largest factor responsible for
      poor reproductive efficiency in buffaloes. Therefore, oestrus synchronization
      (OS) and fixed-time artificial insemination (AI) is considered an alternative
      approach to enhance reproductive efficiency in buffaloes. Thus, the present study
      was carried out to study the efficacy of modified Ovsynch protocol with fixed
      time insemination in post-partum anoestrus buffaloes. MATERIALS AND METHODS:
      Total 50 post-partum anoestrus dairy buffaloes were selected and randomly divided
      into 5 Groups, each comprising ten animals (n=10). Animals of Group I received
      buserelin acetate 10 MUg(GnRH) at day 0 and 9, and prostaglandin F2alpha
      (PGF2alpha) at day 7; in Group II similar to Group I except double dose of Gn RH
      (20 MUg) at day 0; in Group III, similar to Group I plus additional
      administration of insulin on day 0, 1 and 2; in Group IV, similar to Group II
      plus additional administration of insulin on day 0,1 and 2; in Group V similar to
      Group I except replacement of first Gn RH with insulin on day 0,1 and 2. Animal
      of all groups were inseminated at fixed time using frozen semen at 60 h and 72 h
      after PGF2alpha administration and confirmed for pregnancy at day 60 post
      insemination. RESULTS: The results revealed satisfactory and comparable
      synchronization of oestrus (60-80%) and conception rate (20-40%) among the
      various treatment groups in the present study. The better synchronization was
      observed in modified protocols. However, non-significantly higher conception rate
      was recorded in modified Ovsynch protocol (40% each in Group II-V) as compared to
      20% in Group-I (p>0.05). CONCLUSION: In this study comparatively higher OS and
      conception following insulin modified Ovsynch based timed AI protocols in post
      partum anoestrus buffaloes was found satisfactory and comparable.

PMID- 27047089
TI  - Tick-borne infections in human and animal population worldwide.
AB  - The abundance and activity of ectoparasites and its hosts are affected by various
      abiotic factors, such as climate and other organisms (predators, pathogens and
      competitors) presenting thus multiples forms of association (obligate to
      facultative, permanent to intermittent and superficial to subcutaneous) developed
      during long co-evolving processes. Ticks are ectoparasites widespread globally
      and its eco epidemiology are closely related to the environmental conditions.
      They are obligatory hematophagous ectoparasites and responsible as vectors or
      reservoirs at the transmission of pathogenic fungi, protozoa, viruses, rickettsia
      and others bacteria during their feeding process on the hosts. Ticks constitute
      the second vector group that transmit the major number of pathogens to humans and
      play a role primary for animals in the process of diseases transmission. Many
      studies on bioecology of ticks, considering the information related to their
      population dynamics, to the host and the environment, comes possible the
      application and efficiency of tick control measures in the prevention programs of
      vector-borne diseases. In this review were considered some taxonomic,
      morphological, epidemiological and clinical fundamental aspects related to the
      tick-borne infections that affect human and animal populations. 

PMID- 27047091
TI  - Assessment of expected breeding values for fertility traits of Murrah buffaloes
      under subtropical climate.
AB  - AIM: The aim of the present study was to assess the influence of temperature and
      humidity prevalent under subtropical climate on the breeding values for fertility
      traits viz. service period (SP), pregnancy rate (PR) and conception rate (CR) of
      Murrah buffaloes in National Dairy Research Institute (NDRI) herd. MATERIALS AND
      METHODS: Fertility data on 1379 records of 581 Murrah buffaloes spread over four
      lactations and climatic parameters viz. dry bulb temperature and relative
      humidity (RH) spanned over 20 years (1993-2012) were collected from NDRI and
      Central Soil and Salinity Research Institute, Karnal, India. Monthly average
      temperature humidity index (THI) values were estimated. Threshold THI value
      affecting fertility traits was identified by fixed least-squares model analysis.
      Three zones of non-heat stress, heat stress and critical heat stress zones were
      developed in a year. The genetic parameters heritability (h(2)) and repeatability
      (r) of each fertility trait were estimated. Genetic evaluation of Murrah
      buffaloes was performed in each zone with respect to their expected breeding
      values (EBV) for fertility traits. RESULTS: Effect of THI was found significant
      (p<0.001) on all fertility traits with threshold THI value identified as 75.
      Based on THI values, a year was classified into three zones: Non heat stress
      zone(THI 56.71-73.21), HSZ (THI 75.39-81.60) and critical HSZ (THI 80.27-81.60).
      The EBVfor SP, PR, CR were estimated as 138.57 days, 0.362 and 69.02% in non-HSZ
      while in HSZ EBV were found as 139.62 days, 0.358 and 68.81%, respectively. EBV
      for SP was increased to 140.92 days and for PR and CR, it was declined to 0.357
      and 68.71% in critical HSZ. CONCLUSION: The negative effect of THI was observed
      on EBV of fertility traits under the non-HSZ and critical HSZ Thus, the influence
      of THI should be adjusted before estimating the breeding values for fertility
      traits in Murrah buffaloes.

PMID- 27047092
TI  - Variations of motility and survival with storage time at 4 degrees C of
      epididymal spermatozoa Ouled-Djellal breed rams in Eastern Algeria.
AB  - AIM: The aim of this study was to evaluate some reproduction performances in
      Ouled-Djellal rams. MATERIALS AND METHODS: This study involved genital organs
      removed after slaughter from 54 rams at the municipal slaughterhouse of Batna
      (East Algeria). RESULTS: The measurements of survival and mobility of epididymal
      sperm followed at 0, 24, 48 and 72 h after collection, revealed significant
      (p<0.05) to highly significant differences (p>0.001) according to time. Thus,
      concerning the sperm motility the values were 91.00+/-2.40%, 89.20+/-2.40%,
      77.00+/-6.20% and 62.60+/-1.20% at 0, 24, 48 and 72 h, respectively. Indeed, in
      live sperm, the viability rates were 82.15+/-1.48%, 77.67+/-1.74%, 66.56+/-1.95%
      and 52.30+/-1.46% at 0, 24, 48 and 72 h, respectively. CONCLUSION: This study
      revealed that epididymal spermatozoa stored at 04 degrees C for 72 h kept their
      mobility and vitality at nearly a half of their the original parameters.

PMID- 27047093
TI  - Biological and molecular characterization of classical swine fever challenge
      virus from India.
AB  - AIM: The aim of this study was biological and molecular characterization of
      classical swine fever (CSF) challenge virus from India. MATERIALS AND METHODS:
      CSF challenge virus maintained at Division of Biological standardization was
      experimentally infected to two seronegative piglets. The biological
      characterization was done by clinical sign and symptoms along with postmortem
      findings. For molecular characterization 5'-nontranslated region, E2 and NS5B
      regions were amplified by reverse transcription polymerase chain reaction and
      sequenced. The sequences were compared with that of reference strains and the
      local field isolates to establish a phylogenetic relation. RESULTS: The virus
      produced symptoms of acute disease in the piglets with typical post-mortem
      lesions. Phylogenetic analysis of the three regions showed that the current
      Indian CSF Challenge virus is having maximum similarity with the BresciaX strain
      (USA) and Madhya Pradesh isolate (India) and is belonging to subgroup 1.2 under
      Group 1. CONCLUSION: Based on biological and molecular characterization of CSF
      challenge virus from India is described as a highly virulent virus belonging to
      subgroup 1.2 under Group 1 along with some field isolates from India and Brescia
      strain.

PMID- 27047094
TI  - Neutrophil dynamics in the blood and milk of crossbred cows naturally infected
      with Staphylococcus aureus.
AB  - AIM: The present study was designed to evaluate the neutrophil dynamics in terms
      of the functional competence during subclinical mastitis (SCM) and clinical
      mastitis (CM). MATERIALS AND METHODS: A total of 146 Karan fries cows were
      screened and were divided into three groups as control (n=12), SCM, n=12 and CM,
      n=12 groups on the basis of California mastitis test scoring, bacteriological
      evaluation, gross and morphological changes in milk and by counting milk somatic
      cell count (SCC). Both blood and milk polymorphonuclear neutrophils (PMNs) were
      isolated in the study. Phagocytic activity (PA) was studied by
      spectrophotometrically; neutrophil extracelluar traps (NETs) were studied by
      scanning electron microscopy (SEM); CD44 was quantified by flow cytometry and
      apoptosis was studied by fluorescent microscopy. RESULTS: Significantly (p<0.05)
      higher SCC, PA was found in milk of CM cows as compared to SCM and control cows.
      Significantly lower (p<0.05) apoptosis was observed in PMNs isolated from both
      blood and milk of CM group of cows when compared to control and SCM group. The
      milk neutrophils of CM group of cows formed NETs as evidenced from the SEM
      images. Surface expression of CD44 revealed a significantly (p<0.05) lower
      expression in milk neutrophils of CM group of cows when compared to SCM and
      control group of cows. CONCLUSION: The study indicated a positive correlation
      between delayed neutrophil apoptosis, persistent staying of neutrophils at the
      site of infection along with formation of NETs as the strategies to fight against
      the pathogens in the udder during Staphylococcal mastitis. The study forms a
      strong base for future molecular research in terms of neutrophil recruitment and
      neutrophil removal from the site of infection.

PMID- 27047095
TI  - Seroprevalence of bluetongue in ruminants of Jharkhand.
AB  - AIM: This study was carried out to assess the presence of anti-bluetongue (BT)
      antibodies in sheep, goat and cattle of different agro-climatic zones of
      Jharkhand. MATERIALS AND METHODS: Serum samples were collected from apparently
      healthy as well as suspected sheep, goat and cattle from different districts of
      Jharkhand covering different agro-climatic zones. Serum samples were screened by
      indirect enzyme linked immunosorbent assay (iELISA) for detecting anti-BT
      antibodies. RESULTS: Out of a total of 480 animal serum samples (sheep-190, goats
      210 and cattle-80) screened, 83 (43.68%) of sheep, 91 (43.33%) of goat and 46
      (57.50%) of cattle sera were found positive. The % positivity ranged between 41%
      and 51% in different agro-climatic zones. The results showed slight higher
      seroprevalence, although not significantly, in cattle than sheep and goats in
      different agro-climatic zones of Jharkhand. CONCLUSIONS: The above data indicate
      widespread prevalence of BT virus antibodies in studied areas. The incidence of
      BT is not detected officially, so far. The present seroprevalence status of BT in
      Jharkhand indicates presence of BT infection in the state for the first time.

PMID- 27047096
TI  - Impact of second line limiting amino acids' deficiency in broilers fed low
      protein diets with rapeseed meal and de-oiled rice bran.
AB  - AIM: To study the impact of deficiency of second line limiting amino acids (SLAA;
      valine, isoleucine and tryptophan) on the production performance and carcass
      characteristics of commercial broilers. MATERIALS AND METHODS: A control (T1)
      corn-soy diet was formulated to contain all essential AA on standardized ileal
      digestible basis; While in T2-a 'moderate SLAA deficit' diet was formulated by
      replacement of soybean meal with 6% rapeseed meal and T3-a 'high SLAA deficit'
      diet was formulated by replacement of soybean meal with 6% de-oiled rice bran.
      Each of these treatments was allotted to six replicates of ten chicks each.
      During the 42 days experimental period, growth performance, carcass parameters
      and intake of metabolizable energy (ME), crude protein (CP) and AA were studied.
      RESULTS: The cumulative body weight gain, feed conversion ratio, carcass cut
      weights and yields of carcass, breast and thighs were decreased (p<0.05) in T3
      compared to T1. The absolute intake of ME, lysine, methionine + cysteine and
      threonine were not affected while intake of CP and all SLAA were reduced in SLAA
      deficit diets. The relative intake of ME, lysine, methionine + cysteine,
      threonine and SLAA reduced in T3 in comparison to T1. The relative weights of
      internal organs were not affected by treatments while the abdominal fat
      percentage was increased linearly to the magnitude of SLAA deficiency.
      CONCLUSION: The deficiency of SLAA decreased performance, carcass yields and
      impaired utilization of ME, CP and AA linearly to the magnitude of the
      deficiency.

PMID- 27047097
TI  - Antibacterial efficacy of ethyl acetate fraction of Psidium guajava leaf aqueous
      extract on experimental Escherichia coli (O78) infection in chickens.
AB  - AIM: This study was desingned to examine the efficacy of ethyl acetate fraction
      of aqueous extracted Psidium guajava leaves on chicks experimentally-infected
      with diarrheagenic strain of Escherichia coli O78. METHODS: A total of 60 ISA
      brown male chicks were randomly divided into 6 Groups of ten chicks each in
      separate cages. Group A was not infected and not treated. Groups B, C and D were
      infected and treated with extracts at a dose of 25, 50 and 100 mg/kg respectively
      for 10 days. Group E was infected and treated with oxytetracycline while Group F
      was infected, but left untreated. Chicks from all groups were closely monitored
      for clinical signs, body weight change and fecal bacterial shedding load during
      the course of the experiment. RESULTS: Diarrhea, vents pasted with feces, drop in
      feed intake accompanied by slow weight gain and decreased activity was observed
      in infected untreated groups. Groups treated with graded doses of the extract
      experienced a dose-dependent decreased in severity of the clinical signs shown
      compared to the infected untreated group. Bacterial shedding load was found to be
      lower in groups treated with the extract and oxytetracycline than those without
      intervention. CONCLUSION: Ethyl acetate soluble fraction of leaf extract of
      Psidium guajava effectively controlled diarrhea and decreased the severity of
      other clinical signs caused by experimental E. coli infections in chicks.

PMID- 27047098
TI  - Somatic cell count and alkaline phosphatase activity in milk for evaluation of
      mastitis in buffalo.
AB  - BACKGROUND AND AIM: Mastitis is a serious disease of dairy animals causing great
      economic losses due to a reduction in milk yield as well as lowering its
      nutritive value. The application of somatic cell count (SCC) and alkaline
      phosphatase activity in the milk for diagnosis of mastitis in buffalo is not well
      documented. Therefore, the present study was conducted to observe the SCC and
      alkaline phosphatase activity for evaluation of mastitis in buffalo. MATERIALS
      AND METHODS: Milk samples of forty apparently healthy lactating buffaloes were
      selected and categorized into five different groups viz. normal buffaloes,
      buffaloes with subclinical mastitis with CMT positive milk samples (+1 Grade),
      (+2 Grade), (+3 Grade), and buffaloes with clinical mastitis with 8 animals in
      each group. The milk samples were analyzed for SCC and alkaline phosphatase
      activity. RESULTS: The levels of SCC (*10(5) cells/ml) and alkaline phosphatase
      (U/L) in different groups were viz. normal (3.21+/-0.179, 16.48+/-1.432),
      subclinical mastitis with CMT positive milk samples with +1 Grade (4.21+/-0.138,
      28.11+/-1.013), with +2 Grade (6.34+/-0.183, 34.50+/-1.034), with +3 Grade
      (7.96+/-0.213, 37.73+/-0.737) and buffaloes with clinical mastitis (10.21+/
      0.220, 42.37+/-0.907) respectively, indicating an increasing trend in the values
      and the difference observed among various group was statistically significant.
      CONCLUSION: In conclusion, the results of the present study indicate that the
      concentration of milk SCC and alkaline phosphatase activity was higher in the
      milk of buffaloes with mastitis than in the milk of normal buffaloes.

PMID- 27047099
TI  - Production and assay of cellulolytic enzyme activity of Enterobacter cloacae WPL
      214 isolated from bovine rumen fluid waste of Surabaya abbatoir, Indonesia.
AB  - AIM: This study aims to produce and assay cellulolytic enzyme activity (endo
      (1,4)-beta-D-glucanase, exo-(1,4)-beta-D-glucanase, and beta-glucosidase, at
      optimum temperature and optimum pH) of Enterobacter cloacae WPL 214 isolated from
      bovine rumen fluid waste of Surabaya Abbatoir, Indonesia. MATERIALS AND METHODS:
      To produce enzyme from a single colony of E. cloacae WPL 214, 98 * 10(10) CFU/ml
      of isolates was put into 20 ml of liquid medium and incubated in a shaker
      incubator for 16 h at 35 degrees C in accordance with growth time and optimum
      temperature of E. cloacae WPL 214. Further on, culture was centrifuged at 6000
      rpm at 4 degrees C for 15 min. Pellet was discarded while supernatant containing
      cellulose enzyme activity was withdrawn to assay endo-(1,4)-beta-D-glucanase, exo
      (1,4)-beta-D-glucanase, and beta-glucosidase. RESULTS: Cellulase enzyme of E.
      cloacae WPL 214 isolates had endoglucanase activity of 0.09 U/ml, exoglucanase of
      0.13 U/ml, and cellobiase of 0.10 U/ml at optimum temperature 35 degrees C and
      optimum pH 5. CONCLUSION: E. cloacae WPL 214 isolated from bovine rumen fluid
      waste produced cellulose enzyme with activity as cellulolytic enzyme of endo
      (1,4)-beta-D-glucanase, exo-(1,4)-beta-D-glucanase and beta-glucosidase.

PMID- 27047100
TI  - Patho-epidemiological study on Genotype-XIII Newcastle disease virus infection in
      commercial vaccinated layer farms.
AB  - AIM: The present research work was carried out to study the patho-epidemiological
      aspects of Genotype-XIII Newcastle disease virus (NDV) infection in commercial
      layer in and around Anand, Gujarat. As the outbreaks have reported in vaccinated
      flocks, it was felt necessary to study the disease with respect to its changing
      pathogenicity and relevant aspects. MATERIALS AND METHODS: The study comprised of
      patho-epidemiology of Newcastle disease (ND) by information collected from
      different layer farms suffering from the disease in relation to incidence pattern
      and mortality, duration of mortality, susceptible age, and loss due to production
      performance. Clinical signs were recorded based on observations. During post
      mortem, gross lesions were also recorded. For histopathological examination
      visceral organs according to lesions were collected in 10% formalin and processed
      slide stained by hematoxylin and eosin for microscopic examination. Cultivation
      of virus was done in embryonated specific pathogen-free (SPF) eggs of 9-11 days
      and isolation of virus was done for haemagglutination (HA) and haemagglutination
      inhibition (HI) test and to identify pathotype of virus by intracerebral
      pathogenicity index (ICPI) test to determine the virulence of virus. The Genotype
      XIII NDV was confirmed by F gene sequence and whole genome sequence. RESULTS:
      During the study mortality due to ND was recorded in 13 layer flocks in spite of
      routine vaccination, which usually contain Genotype-II strain of virus. The
      mortality was observed as high as above 50% with an average of 21.21%. The
      susceptible age for disease was found to be 6-14 weeks. The duration of mortality
      observed was 23 days. The disease resulted in a significant reduction in body
      weight, feed intake and drop in egg production. Majority of the outbreaks
      appeared during extremely hot months of April to June. Greenish diarrhoea was
      frequently seen in birds that survived early in infection. Mortality continued
      for 2-3 weeks and reduced with appearance of torticollis. Gross lesions were
      characterized by multifocal to diffuse hemorrhages around proventricular glands,
      necrotic (diphtheritic) haemorrhagic ulcers throughout the intestine,
      disseminated multiple foci of necrosis and pin-point hemorrhages in the spleen
      parenchyma. The microscopic lesions include focal to diffuse hemorrhages, diffuse
      infiltration of mononuclear cells, necrosis, and degeneration in visceral organs.
      All the 13 farm samples (n=13) resulted in death of all the embryos following
      incubation up to 72 h post-inoculation. All the 13 allantois fluids from field
      samples along with F and R2B vaccine sample were found positive for HA activity,
      which was further confirmed by HI using known NDV serum. The values of ICPI were
      2.0 which were indicative of velogenic nature of the field NDV strain.
      CONCLUSION: The study indicated that presently available live and attenuated
      vaccines which include Genotype-II NDV have failed in protecting the flocks
      against Genotype-XIII and resulted in outbreaks with mortality above 50%. ICPI
      score of 2.0 confirmed that the present outbreaks were due to Genotype-XIII NDV,
      which is velogenic in nature.

PMID- 27047101
TI  - Polymorphism and association of growth hormone gene with growth traits in Sirohi
      and Barbari breeds of goat.
AB  - AIM: The aim was to study the polymorphism of exon 2 and exon 3 of growth hormone
      (GH) gene, to test the polymorphic variants for Hardy-Weinberg equilibrium and to
      investigate association of these polymorphisms with chest girth and paunch girth
      in Sirohi and Barbari breeds of goat. MATERIALS AND METHODS: A total of 80 kids
      involving forty each of Sirohi and Barbari breeds of goat were included in the
      study. A good quality genomic DNA isolated from the whole blood using standard
      protocol were used for polymerase chain reaction (PCR) amplification and products
      obtained on restriction digestion of amplicon with enzyme HaeIII were separated
      on 2% agarose gel, and documented in a gel doc system. The chest girth and paunch
      girth of kids at birth and weekly intervals up to 4 weeks of age and subsequently
      at 2 months, 3 months and 6 months of age were recorded. Allele frequency and
      genotype distribution of polymorphism were tested for Hardy-Weinberg equilibrium
      by program me Genepop package. Association between different genetic variants on
      chest girth and paunch girth were analyzed by least squares analysis employing
      suitable statistical model. RESULTS: The PCR product of genomic DNA isolated from
      kids of Sirohi and Barbari breeds of goat on digestion with the restriction
      enzyme HaeIII revealed two genotypic variants viz., AB and BB. None of the two
      breeds was in Hardy-Weinberg equilibrium for these variants. The least squares
      analysis of variance revealed non-significant effect of GH genotype and breed *
      genotype interaction on chest girth and paunch girth from birth to 180 days of
      age. The effect of breed was highly significant (p<0.01) at all ages. CONCLUSION:
      The present study showed that both the breeds were polymorphic at the exon 2 and
      exon 3 loci of GH gene under study with respect to HaeIII restriction
      endonuclease. None of the breeds was in Hardy-Weinberg equilibrium for this
      region of GH gene. In the present study, no significant association between GH
      genotype and chest girth and paunch girth could be established but comparatively
      higher chest girth and paunch girth were observed for AB genotype across the
      breeds.

PMID- 27047102
TI  - Detection of Salmonella spp. from chevon, mutton and its environment in retail
      meat shops in Anand city (Gujarat), India.
AB  - AIM: The aim of this study was (i) To attempt isolation and identification of
      Salmonella species from samples. (ii) Serotyping of Salmonella isolates. (iii)
      Detection of virulence factor associated genes by polymerase chain reaction
      (PCR). MATERIALS AND METHODS: A total of 284 samples comprised of chevon and
      mutton (112 samples each) as well as 60 samples (20 each of retail meat shops
      environment samples viz. Butchers' hands, knives and log swabs) were collected
      from the retail meat shops in and around Anand City under aseptic precautions.
      Rappaport-vassiliadis soy bean meal broth and tetrathionate broth was used for
      the enrichment of all the samples and inoculation was done on brilliant green
      agar and xylose lysine deoxycholate agar. This was followed by the confirmation
      of isolates using biochemical tests. For the serotyping, isolates were sent to
      the National Salmonella and Escherichia Centre, Central Research Institute,
      Kasauli, Himachal Pradesh. Detection of virulence genes was performed by PCR
      technique using previously reported primer. RESULT: Of 284 meats and retail meat
      shops environment samples, 13 (4.58%) samples were found positive for Salmonella.
      It was interesting to know that incidence of Salmonella was more in mutton
      (6.25%) than chevon (3.57%). In case of meat shop environmental samples 1 (5.00%)
      sample observed positive for Salmonella separately among the butchers' hands and
      knives swabs (Each of 20 samples) examined. Out of 13, eleven isolates detected
      as Salmonella Typhimurium, whereas only two isolates were detected as Salmonella
      Enteritidis. All Salmonella isolates possess invA and stn genes, whereas nine
      isolates had a presence of spvR gene while only five of the isolates revealed the
      presence of spvC gene as shown by in vitro detection of virulence genes by PCR.
      CONCLUSION: Therefore, might be suggested that the good hygiene practices and
      effective control measures should be taken to encourage clean meat production
      with prolonged shelf-life.

PMID- 27047103
TI  - Development of on package indicator sensor for real-time monitoring of meat
      quality.
AB  - AIM: The aim was to develop an indicator sensor for real-time monitoring of meat
      quality and to compare the response of indicator sensor with meat quality
      parameters at ambient temperature. MATERIALS AND METHODS: Indicator sensor was
      prepared using bromophenol blue (1% w/v) as indicator solution and filter paper
      as indicator carrier. Indicator sensor was fabricated by coating indicator
      solution onto carrier by centrifugation. To observe the response of indicator
      sensor buffalo meat was packed in polystyrene foam trays covered with PVC film
      and indicator sensor was attached to the inner side of packaging film. The
      pattern of color change in indicator sensor was monitored and compared with meat
      quality parameters viz. total volatile basic nitrogen, D-glucose, standard plate
      count and tyrosine value to correlate ability of indicator sensor for its
      suitability to predict the meat quality and storage life. RESULTS: The indicator
      sensor changed its color from yellow to blue starting from margins during the
      storage period of 24 h at ambient temperature and this correlated well with
      changes in meat quality parameters. CONCLUSIONS: The indicator sensor can be used
      for real-time monitoring of meat quality as the color of indicator sensor changed
      from yellow to blue starting from margins when meat deteriorates with advancement
      of the storage period. Thus by observing the color of indicator sensor quality of
      meat and shelf life can be predicted.

PMID- 27047104
TI  - Typing of Staphylococcus aureus obtained from mastitic milk of cattle and buffalo
      on the basis of two virulence-associated genes (spa and clfA).
AB  - AIM: The present study was undertaken to type Staphylococcus aureus isolates from
      cattle and buffalo mastitic milk on the basis of spa (X-region) and clfA genes,
      both responsible for producing virulence factors. MATERIAL AND METHODS: In the
      present investigation S. aureus isolates were isolated as per standard protocols.
      Typing of S. aureus was carried out by molecular detection of spa and clfA gene
      by polymerase chain reaction. RESULTS: All the 32 isolates from cattle (16) and
      buffalo (16) were divisible into seven spa types with amplicon sizes ranging
      between 120 and 380bp. The cattle isolates produced seven different spa amplicons
      of 120, 150, 200, 250, 280, 300, and 330 bp with 3, 4, 6, 8, 10, 11 and 12 number
      of tandem repeats, respectively whereas buffalo isolates were divisible into five
      spa types with amplicons of 150, 200, 250, 330 and 380 bp having calculated
      number of repeats of 5, 7, 9, 12, and 14, respectively. Of the total isolates, 24
      were considered pathogenic on the basis of more than seven number of tandem
      repeats. In the present investigation, clfA gene was amplified in 27 isolates
      from cattle and buffalo producing two different amplicons of 900 and 1000 bp
      sizes showing polymorphism. The most (71.80%) of the isolates produced amplicons
      of 900 bp while amplicon size of 1000 bp was produced by four (12.5%) of the
      isolates. CONCLUSION: The presence of these genes with a wide degree of
      polymorphism confirmed the pathogenic potential of S. aureus and their
      association with clinical manifestations in mastitis among cattle and buffalo.

PMID- 27047105
TI  - Prevalence of common canine digestive problems compared with other health
      problems in teaching veterinary hospital, Faculty of Veterinary Medicine, Cairo
      University, Egypt.
AB  - AIM: The present study was conducted to ascertain the prevalence of common
      digestive problems compared to other health problems among dogs that were
      admitted to the teaching veterinary hospital, faculty of veterinary medicine,
      Cairo University, Egypt during 1 year period from January to December 2013. Also,
      study the effect of age, sex, breeds, and season on the distribution of digestive
      problems in dogs. MATERIALS AND METHODS: A total of 3864 dogs included 1488
      apparently healthy (included 816 males and 672 females) and 2376 diseased dogs
      (included 1542 males and 834 females) were registered for age, sex, breed, and
      the main complaint from their owners. A complete history and detailed clinical
      examination of each case were applied to the aids of radiographic,
      ultrasonographic, and endoscopic examination tools. Fecal examination was applied
      for each admitted case. Rapid tests for parvovirus and canine distemper virus
      detection were also performed. RESULTS: A five digestive problems were commonly
      recorded including vomiting, diarrhea, concurrent vomiting with diarrhea,
      anorexia, and constipation with a prevalence (%) of 13.6, 19.1, 10.1, 13.1, and
      0.5 respectively while that of dermatological, respiratory, urinary,
      neurological, cardiovascular, auditory, and ocular problems was 27.9, 10.5, 3.3,
      0.84, 0.4, 0.25, and 0.17 (%) respectively. This prevalence was obtained on the
      basis of the diseased cases. Age and breed had a significant effect on the
      distribution of digestive problems in dogs (p<0.001). Gender had an effect on the
      distribution of digestive problems with significant (p<=0.01) while season had a
      non-significant effect (p>0.05) on the distribution of such problems. CONCLUSION:
      Digestive problems were the highest recorded problems among dogs, and this was
      the first records for such problems among dogs in Egypt. Age, gender, and breeds
      had a significant effect on the distribution of the digestive problems in dogs
      while season had a non-significant effect on the distribution of such problems.
      The present data enable veterinarians in Egypt to ascertain their needs for
      diagnostic tools and medication that must be present at any pet clinic.

PMID- 27047106
TI  - Doppler sonography for evaluation of hemodynamic characteristics of fetal
      umbilicus in Beetal goats.
AB  - AIM: The objective of this study was to evaluate the hemodynamic characteristics
      of umbilical vessels in healthy pregnant Beetal goats. MATERIALS AND METHODS:
      Doppler examinations were performed from day 20 to 120 of gestation, twice in
      week from day 20 to 60 and once in week from day 60 to 120 of gestation on six
      goats. RESULTS: Free floating umbilical cord was identified on day 39 of
      gestation. The umbilical cord waveform was characterized by the simultaneous
      presence of arterial and venous flow. The pattern of blood flow in the umbilical
      artery was represented as saw tooth pattern above the baseline. Pattern of blood
      flow in umbilical vein was flat and wavy in nature; presented below the baseline.
      Peak systolic velocity (PSV) increased significantly from day 39 to 67 and
      further between 98 and 120 days of gestation (p<0.05), but there was no
      significant increase or decrease in end-diastolic velocity (EDV). Pulsatility
      index (PI) value was increased significantly during 42 to 48 days of gestation
      and decreased significantly from 98 to 105 days of gestation. On other days,
      there was no significant increase or decrease. Value of resistance index (RI) was
      more stable than PI values as there was no significant increase or decrease in RI
      value. CONCLUSIONS: From the present study, it is reasonable to conclude that the
      normal blood flow parameters like PI, RI, PSV and EDV during gestation might be
      helpful in assessment of antenatal development of fetus in the goat. This work
      provides the basis for further contribution in diagnosing and monitoring high
      risk pregnancy in this species.

PMID- 27047107
TI  - Study on hematological alterations induced by amphistomosis in buffaloes.
AB  - AIM: The study was undertaken to compare the alterations in the hematological
      parameters in buffaloes suffering from Amphistomosis with normal buffaloes and to
      correlate it with the subclinical infection that is hard to diagnose. MATERIALS
      AND METHODS: Blood samples from 50 amphistomes infected as well as 50 non
      infected buffaloes from slaughter houses were taken into vacutainer tubes
      containing ethylene diamine tetraacetic acid for estimation of various
      hematological parameters by Automatic Analyzer Hema-2062 manufactured by
      Analytical Technologies Ltd. RESULT: There was a significant reduction in the
      mean hemoglobin, total leukocyte count, total erythrocyte count and packed cell
      volume and significant increase in the neutrophils count and eosinophil count of
      infected buffaloes as compared to the non-infected buffaloes respectively.
      CONCLUSION: Amphistomosis is characterized by severe neutrophilia, eosinophilia,
      and anemia. Anemia of high intensity along with hepatic damage can lead to the
      death of the animal in severe cases. Alterations in the Hematological parameters
      can be used as an indicator to diagnose and check the severity of amphistomosis
      especially in young ones and in subclinical infection.

PMID- 27047108
TI  - Comparative antibiogram of coagulase-negative Staphylococci (CNS) associated with
      subclinical and clinical mastitis in dairy cows.
AB  - AIM: The present study was planned to determine the in vitro antibiotic
      susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from
      clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity
      profile will be helpful to recommend early therapy at the field level prior to
      availability of CST results. MATERIALS AND METHODS: The milk samples from cases
      of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary
      and Animal Sciences University, Ludhiana and those of subclinical mastitis
      collected during routine screening of state dairy farms, were subjected to
      microbial culture. Identification of CNS organisms was done by standard
      biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics
      belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical
      isolates: 41, subclinical isolates: 17). RESULTS: Isolates were highly
      susceptible to chloramphenicol (98.3%), gentamicin (93.1%), streptomycin (91.4%),
      linezolid (91.4%), ceftixozime (87.9%), cloxacillin (86.2%), clotrimazole
      (86.2%), bacitracin (86.2%), enrofloxacin (84.5%) and ceftrioxone + tazobactum
      (70.7%), while resistance was observed against amoxicillin (77.6%), penicillin
      (75.9%), ampicillin (74.1%) and cefoperazone (51.7%). Overall, isolates from
      clinical cases of mastitis had a higher resistance than subclinical isolates.
      CONCLUSION: CNS isolates were susceptible to chloramphenicol, gentamicin and
      streptomycin, while higher resistance was recorded against routinely used
      penicillin group.

PMID- 27047109
TI  - Trotter welfare's protection: A legislative perspective.
AB  - The Council of Europe's activities in the field of animal welfare are
      particularly noteworthy and comprise the elaboration of several norms for the
      protection of animals. Concerning the specific European Directive, Regulations or
      Convention for the protection of animals, the Authors underline the missing of
      specifics recommendations concerning the welfare of sport horses and especially
      of trotters. Guidelines are reported by regulation of equestrian sports. The
      paper's purpose is to give practical elements to individuate the welfare state
      and to promote a clear regulation on welfare, care and protection of trotters. 

PMID- 27047110
TI  - Occurrence and Distribution of bovine tuberculosis (Mycobacterium bovis) in
      Slaughtered cattle in the abattoirs of Bauchi State, Nigeria.
AB  - AIM: This study was aimed to determine the prevalence of bovine tuberculosis
      (bTB) in slaughtered cattle in Bauchi State, Nigeria. The cause (s) of grossly
      suspected bTB lesions encountered at the abattoirs during post-mortem (PM), as
      whether due to Mycobacterium bovis alone or together with other acid fast bacilli
      (AFB). MATERIALS AND METHODS: A cross-sectional abattoir based study was
      conducted on 800 cattle slaughtered in the Northern, Central and Southern zonal
      abattoirs of Bauchi State, Nigeria, from June to August 2013; using PM meat
      inspection, Ziehl-Neelsen staining (ZN) and confirmatory polymerase chain
      reaction (PCR) techniques. RESULTS: The occurrence of bTB lesions from the organs
      of slaughtered cattle in Bauchi State, showed that the lungs had the highest
      number of suspected tissues 65 (54.20%), followed by the lymph nodes 28 (23.30%)
      while the heart, liver, spleen, intestines and mammary glands had the other 8.3%,
      6.7%, 5.0%, 1.7%, and 0.8%, suspected tissues respectively. By ZN microscopic
      staining all 100% (2/2) of the intestines were positive for bTB, followed by the
      heart with 50% (5/10), then the lungs 29.23% (19/65); while the liver, lymph
      nodes, and spleen had 25%, 21.43% and 16.67% respectively were tested positive
      for bTB. It was only the mammary gland that tested negative for bTB in all the
      suspected tissues sampled. By PCR, the intestines had the highest positive bTB
      with 100% (2/2), followed by the liver with 12.5% (1/8), and then the lungs with
      7.8% (5/65). The lymph nodes had 7.14% (2/28) tissues that tested positive for
      bTB. However, the spleen, heart and mammary gland were all tested negative with
      0%; indicating that the false positive for bTB detected by ZN were confirmed by
      PCR. While based on the location of the abattoirs in the three senatorial zones
      of Bauchi State, Bauchi zonal abattoir had the highest number of suspected bTB
      cases 75 (62.50%), followed by Katagum zonal slaughter house with 32 (26.7%) and
      then Misau with 13 (10.8%). By the ZN staining technique, there were 25 (33.33%)
      positivity in Bauchi Zonal abattoir, while Katagum and Misau abattoirs had 9
      (28.13%) and 1 (7.72%) positive respectively. By the PCR technique, 9 (12.00%), 1
      (3.13%) and 0 (0.00%) positive cases were recorded for Bauchi, Katagum and Misau
      abattoirs respectively. CONCLUSION: The present study estimated the prevalence
      rate of bTB in Bauchi State, using PM, ZN and PCR techniques at 15.0%, 29.16% and
      8.33%, respectively. Bovine TB lesions found at PM were not all due to M. bovis
      alone, as other MTBC and AFB organisms may cause bTB-like lesions that were
      excluded by PCR specific primers. The prevalence of bTB was higher in Bauchi
      abattoir that supplies larger population of the state with beef. These findings
      also demonstrate the urgent need for public health authorities in the state to
      intervene in the control of the zoonotic bTB.

PMID- 27047111
TI  - Bronchoalveolar lavage is an ideal tool in evaluation of local immune response of
      pigs vaccinated with Pasteurella multocida bacterin vaccine.
AB  - AIM: The aim was to study the bronchoalveolar lavage (BAL) technique in
      evaluating the local immune response of pig immunized with Pasteurella multocida
      bacterin vaccine. MATERIALS AND METHODS: Weaned piglets were immunized with
      formalin-inactivated P52 strain of P. multocida bacterin and evaluated for
      pulmonary immune response in BAL fluid. BAL was performed before vaccination and
      at different post vaccination days. The BAL fluid was assayed using enzyme-linked
      immunosorbent assay to study the development of P. multocida specific antibody
      isotypes and also evaluated for different cell populations using standard
      protocol. RESULTS: The average recovery percentage of BAL fluid varies from 58.33
      to 61.33 in vaccinated and control group of piglets. The BAL fluid of vaccinated
      pigs showed increase in antibody titer up to 60(th) days post vaccination (8.98+/
      0.33), IgG being the predominant isotype reached maximum titer of 6.12+/-0.20 on
      45(th) days post vaccination, followed by IgM and a meager concentration of IgA
      could be detected. An increased concentration of the lymphocyte population and
      induction of plasma cells was detected in the BAL fluid of vaccinated pigs.
      CONCLUSION: Though intranasal vaccination with P. multocida plain bacterin
      vaccine could not provoke a strong immune response, but is promising as
      lymphocyte population was increased and plasma cells were detected. BAL can be
      performed repeatedly up to 3/4 months of age in pigs to study pulmonary immune
      response without affecting their health.

PMID- 27047112
TI  - Diagnosis of peste des petits ruminants infection in small ruminants through in
      house developed Indirect ELISA: Practical considerations.
AB  - AIM: The work was conducted to diagnose peste des petits ruminants (PPR) outbreak
      through an in house developed indirect ELISA (thereafter referred as iELISA) its
      comparison with other available diagnostic tests and description of practical
      considerations in its development, utility and limitations. MATERIALS AND
      METHODS: An outbreak resembled to PPR occurred in two different places of
      southern Gujarat viz. Vapi and Navsari, affecting 622 animals, including both
      goat (n = 476) and sheep (n = 146). Animals displayed the typical signs of PPR at
      Vapi; however diarrhea was the inconsistent feature in animals of Navsari. The
      affection caused morbidity of 100% and mortality were 73.68% (n = 392/532) and
      56.67% (n = 51/90) in Vapi and Navsari outbreaks, respectively. Relevant ante
      mortem and post mortem samples were collected from representative animals. At the
      outset of the epidemic no kit was available with us, so agar gel immunodiffusion
      (AGID) was carried out and a commercial ELISA (cELISA) kit was ordered for making
      diagnosis through antibody demonstration. Meanwhile, an iELISA was developed in
      house using PPR vaccine as antigen and protein G conjugated HRPO antibody as
      detector. Histopathology and results of sandwich ELISA were also used to diagnose
      PPR virus (PPRV) in the outbreak. RESULTS: The iELISA developed had detected PPRV
      antibodies in 22/24 samples (91.66%). Significant difference was observed in
      disease sensitivity pattern of two species by Chi-square test. While AGID failed
      to detect antibodies in any sample. Results were reconfirmed by comparing with
      commercially available cELISA kit. CONCLUSION: PPR is an economically important
      disease and for the rapid diagnosis of PPR the in house developed antibody
      capture iELISA can be a suitable cost effective alternative.

PMID- 27047113
TI  - Evaluation of different egg quality traits and interpretation of their mode of
      inheritance in White Leghorns.
AB  - AIM: The experiment was carried out to evaluate different external and internal
      egg quality traits and to figure out their mode of inheritance from a set of
      hierarchically classified data. MATERIALS AND METHODS: The data collected from
      548 progenies (1 egg from each progeny) of 282 dams mated to 47 sires (1 sire
      mated to 6 dams) of a White Leghorn flock were used in the present study.
      Phenotypic means and their standard errors were calculated for all the quality
      traits. Heritabilities were estimated for these traits separately from "sire,"
      "dam" and "sire+dam" (full-sib) components of variance using Statistical Package
      for Social Sciences-17 program. RESULTS: External quality traits such as; egg
      weight, length, width, shape index, surface area, shell weight, shell thickness,
      shell ratio, and internal quality traits such as; length, width, height, and
      weight of albumen and yolk, albumen index, albumen ratio, Haugh unit (H.U.), yolk
      diameter, yolk index, yolk ratio, and yolk albumen ratio were measured in 548
      eggs of the experimental White Leghorn flock. The eggs were found to have optimum
      weight (57.78+/-0.20 g), shape index (73.53+/-0.18) and shell characteristics (6
      g, 0.32 mm) as per its genetic potential. Higher values for albumen height
      (8.41+/-0.04) mm and H.U. (92.00+/-0.19) are attributable to the freshness of
      eggs and proper age of hens. Heritability estimates from "sire" component of
      variance were higher than "dam" and "sire+dam" components for the traits like egg
      weight, length, width, shape index, surface area, albumen width, albumen index,
      H.U., yolk width, yolk height, yolk weight, and yolk index whereas for rest of
      the traits the values estimated from "dam" component were higher. Estimates from
      "sire+dam" component were intermediate to the estimates derived from "sire" and
      "dam" components. CONCLUSION: The heritability estimates from different egg
      quality traits were moderate to high. Since most of the traits have high
      heritability values, these traits can be improved by mass selection.

PMID- 27047114
TI  - Effect of supplementation of lysine producing microbes vis-a-vis source and level
      of dietary protein on performance and egg quality characteristics of post-peak
      layers.
AB  - AIM: The aim was to study the effect of supplementation of lysine producing
      microbes (LPM) as an in vivo source of lysine on performance and egg quality
      characters of post-peak layers. MATERIALS AND METHODS: BIS (1992) specified diets
      (except crude protein [CP] and lysine) were prepared using either soybean meal
      (SBM) or groundnut extractions (GNE) or sunflower extractions (SFE) with 16 and
      15% CP resulting in six control diets. Further, each control diet was fortified
      with either synthetic lysine or LPM to meet BIS (1992) specified lysine
      requirement resulting in the set of 12 test diets. Each of the eighteen diets was
      offered to quadruplets groups of 4 post-peak (52 weeks) commercial laying hens in
      each. The trial lasted for 119 days. RESULT: The results revealed that the feed
      consumption and body weight changes and Roche yolk color and yolk index were
      significantly (p <= 0.05) different among different treatments. However, egg
      production, feed efficiency, egg weight, egg shape index, Haugh unit score,
      albumen index and shell thickness, and net returns remained non-significant (p <=
      0.05) among different treatments. Among main factors, protein level (16% and 15%
      CP) made a significant (p <= 0.05) difference in egg production (79.6 and 75.1%)
      and feed efficiency (2.64 and 2.81 kg feed/kg egg mass, respectively). Among
      protein source GNE- and SFE-based diet fed groups showed significantly (p < 0.0%)
      higher feed consumption and body weight gain than SBM based diets fed birds. Yolk
      color (7.0, 7.3 and 7.3, respectively) and yolk index (0.40, 0.38 and 0.43,
      respectively) were significantly (p <= 0.05) different from the protein sources.
      CP level and Protein source interaction effects showed significant differences in
      albumen index and Haugh unit score. CONCLUSION: Optimum level of protein (16% CP)
      and GNE as a source of protein tended to be superior in increasing the
      performance and egg characteristics of post-peak layers and supplementation of
      lysine in either synthetic or LPM form found to be beneficial in optimizing their
      performance.

PMID- 27047115
TI  - Effect of species, breed, and age on bacterial load in bovine and bubaline semen.
AB  - AIM: The present study was conducted to investigate the effect of species, breed
      and age on bacterial load in fresh and frozen semen of Cattle and Buffalo bull.
      MATERIALS AND METHODS: Present study covered 56 cow and 10 buffalo bulls
      stationed at Central Semen Station Anjora, Durg (Chhattisgarh). Impact of breeds
      on bacterial load in semen was assessed using six breeds of cattle viz. Sahiwal,
      Gir, Red Sindhi, Tharparkar, Jersey and Holstein Friesian (HF) cross. Cow bulls
      were categorized into four different groups based on their age (<4 years, 4-5
      years, 5-6 years and > 6 years) to study variation among age groups. Bacterial
      load was measured in fresh and frozen semen samples from these bulls using the
      standard plate count (SPC) method and count was expressed as colony forming unit
      (CFU) per ml of semen. RESULTS: Higher bacterial load was reported in fresh (2.36
      * 10(4) +/- 1943 CFU/ml) and frozen (1.00 * 10 +/- 90 CFU/ml) semen of cow bulls
      as compared to buffalo bulls (1.95 * 10(4) +/- 2882 and 7.75 * 10(2) +/- 160
      CFU/ml in fresh and frozen semen, respectively). Jersey bull showed significantly
      higher bacterial count (p < 0.05) both in fresh (4.07 * 10(4) +/- 13927 CFU/ml)
      and frozen (1.92 * 10(3) +/- 178 CFU/ml) semen followed by HF cross, Sahiwal,
      Gir, Red Sindhi and Tharparkar bull. Bulls aged < 4 years and more than 6 years
      yielded increased bacterial load in their semen. Although a minor variation was
      reported between species and among age groups, no significant differences were
      measured. CONCLUSION: Bacterial load in semen did not differ significantly
      between species and age groups; however significant variation was reported among
      different breeds. Bulls of Jersey breed showed significantly higher bacterial
      load in semen as compared to the crossbred and indigenous bull.

PMID- 27047116
TI  - Antibiotic residues in milk and eggs of commercial and local farms at Chittagong,
      Bangladesh.
AB  - AIM: The study was conducted to detection and determination of concentration or
      level of antibiotic residues in milk and egg of local and commercial farms at
      Chittagong during December 2011 to June 2012. MATERIALS AND METHODS: A total of
      400 (200 milk and 200 egg) samples were collected from local and commercial dairy
      cows and local scavenging and commercial poultry farms, respectively. Microbial
      inhibition test and thin layer chromatography were used for screening and ultra
      high performance liquid chromatography was used to estimate the concentrations of
      antibiotic residues in samples. RESULTS: Tetracycline, amoxicillin, and
      ciprofloxacin residues were significantly (p <= 0.05) higher in commercial farms
      than local. The boiling insignificantly (p>0.05) reduced residues level in milk
      and egg. The average concentrations of amoxicillin residue in local milk,
      commercial milk, local egg, and commercial egg were 9.84 ug/ml, 56.16 ug/ml,
      10.46 ug/g and 48.82 ug/g, respectively, in raw samples and were reduced to 9.81
      ug/ml, 55.54 ug/ml, 10.29 ug/g, and 48.38 ug/g, respectively, after boiling.
      CONCLUSIONS: Proper maintaining of the withdrawal period and development of
      active surveillance system are highly recommended for public health security.

PMID- 27047117
TI  - Effect of climatic variables on production and reproduction traits of colored
      broiler breeder poultry.
AB  - AIM: The present study was conducted to investigate the important climatic
      variables affecting production and reproduction in a broiler breeder flock.
      MATERIALS AND METHODS: The experiment was conducted for a period of 1 year on
      colored synthetic female line male and female poultry birds. 630 female progeny
      and 194 male progenies from 69 sires and 552 dams produced in four consecutive
      hatches at an interval of 10 days were used for the present study. Each of the
      seven, body weight and reproduction traits were regressed with nine environmental
      variables. Initially, the data were subjected to hatch effect and sire effect
      corrections through best linear unbiased estimator (BLUE) method and, then,
      multiple linear regressions of environmental variables on each trait were
      applied. RESULT: The overall regression was significant (p<0.01) in all traits
      except 20 week age body weight of females. The R(2) value ranged from 0.12 to
      0.90 for the traits. Regression coefficient values (b values) for maximum
      temperature and minimum temperature were significant (p<0.05) on 5(th) week age
      body weight of males. Similarly, evaporation and morning relative humidity (RH)
      was significant (p<0.05) for 5(th) week age body weight of females. Almost all b
      values were significant (p<0.05) for egg production up to 40 week age. The b
      values representing rainfall, morning RH, afternoon RH, sunshine hours, and rainy
      days were significant (p<0.05) on bodyweight at 20 week age. All environmental
      variables except maximum temperature and minimum temperature were significant
      (p<0.05) on body weight of females at 20 weeks of age. Age at sexual maturity was
      regressed significantly (p<0.05) with evaporation, afternoon RH whereas, egg
      shape index was regressed significantly (p<0.05) with a maximum temperature,
      evaporation and afternoon RH. CONCLUSION: The result indicated that various
      environmental variables play a significant role in production and reproduction of
      breeder broiler poultry. Controlling these variables in adverse weathers may
      increase production.

PMID- 27047118
TI  - Prevalence of antibiotic resistant Staphylococcus aureus from raw milk samples
      collected from the local vendors in the region of Tirupathi, India.
AB  - AIM: The study was carried out with the aim to identify the suitability of the
      milk for consumer use with special reference to Staphylococcus aureus from milk
      samples collected from various local vendors and determine the antibiotic
      susceptibility pattern of those positive isolates. MATERIALS AND METHODS: A total
      of 110 milk samples were collected from the local milk vendors in and around
      Tirupathi region of India. All the samples were enriched with buffered peptone
      water in 9:1 ratio and the then inoculated on baird parker agar medium with added
      2% egg yolk tellurite emulsion as selective medium for S. aureus and confirmed
      with mannitol salt agar, Gram's staining and biochemical tests. The typical
      cultural characters with coagulase-positive samples were taken as positive
      samples the positive samples were tested for antibiotic susceptibility with 10
      different antibiotics by employing disc diffusion method. RESULTS: Prevalence of
      coagulase-positive S. aureus was 39.09% (43/110) from the milk samples. The
      antibiotic susceptibility test of positive isolates showed high resistant toward
      penicillin G 37/43 (86.04%) and ampicillin 32/43 (74.42%), and also showed
      resistant to methicillin 6/43 (13.95%), cephalothin 6/43 (13.95%), tetracycline
      6/43 (13.95%), ciprofloxacin 4/43 (9.30%), enrofloxacin 3/43 (6.97%), cefoxitin
      2/43 (4.65%), gentamicin 2/43 (4.65%), and co-trimoxazole 2/43 (4.65%). Many
      individual isolates showed resistant against two or more antibiotics in our
      study. CONCLUSION: The above study results show that the milk samples collected
      from local vendor having S. aureus, which can induce disease condition as well as
      antibiotic resistant to the humans particularly young children and old age
      peoples by means of consumption of raw milk and its products. This is the public
      health issue, which needs to be solved by educating the local vendors regarding
      health problems related to unhygienic milk supply and make the awareness among
      the consumers about this hazards and preventive measures.

PMID- 27047119
TI  - Effect of L-carnitine supplementation on growth performance, nutrient
      utilization, and nitrogen balance of broilers fed with animal fat.
AB  - AIM: This experiment was conducted to evaluate the effect of L-carnitine
      supplementation on growth performance, nutrient utilization and nitrogen balance
      in broilers fed with animal fat. MATERIALS AND METHODS: 80 day-old Cobb
      commercial broiler chicks were randomly assigned into two dietary treatment
      groups with four replicates of ten chicks each. The diets were isonitrogenous and
      isocaloric. The birds in both the control (T1) and treatment group (T2) were fed
      with a diet having 5% animal fat, while the treatment group (T2) was supplemented
      with 900 mg of L-carnitine. The birds were fed with standard broiler starter
      ration up to 4 weeks of age and finisher ration up to 6 weeks of age. RESULTS:
      The average body weight (g), cumulative feed intake (g) and cumulative feed
      conversion ratio belonging to groups T1 and T2 at 6(th) week of age were 2091.25
      and 2151.11, 3976.49 and 4171.68, 1.97 and 1.96 respectively. The percentage
      availability of the nutrients of two experimental rations T1 and T2 was 68.23 and
      68.00 for dry matter, 58.72 and 55.98 for crude protein, 73.85 and 71.35 for
      ether extract, 34.19 and 33.86 for crude fiber, 79.18 and 79.59 for nitrogen free
      extract, 70.24 and 70.03 for energy efficiency and nitrogen balance (g/day) were
      2.35 and 2.39, respectively. CONCLUSION: This study suggests that the
      supplementation of 900 mg L-carnitine in diet with added animal fat had no effect
      on growth performance, nutrient utilization, and nitrogen balance of broilers.

PMID- 27047120
TI  - Clinico-hemato-biochemical profile of dogs with liver cirrhosis.
AB  - AIM: The aim of this study was to determine the relevant tools in the diagnosis
      of liver cirrhosis in dogs. MATERIAL AND METHODS: A total of 140 dogs presented
      at Veterinary Teaching Hospital, Guru Angad Dev Veterinary and Animal Sciences
      University, Ludhiana, showing clinical signs of hepatic insufficiency were
      subjected to clinico-hemato biochemical, urological, ultrasonographic (USG), and
      USG guided fine-needle biopsy examinations by standard methods. On the basis of
      these results, 6 dogs out of 140 dogs were found to be suffering from liver
      cirrhosis. Six clinically healthy dogs constituted the control group. RESULTS:
      The dogs suffering from liver cirrhosis manifested inappetence, halitosis,
      abdominal distension, weight loss, melena, icterus, anemia, and neutrophilic
      leukocytosis with the left shift. Levels of hemoglobin, lymphocytes, packed cell
      volume, mean corpuscular volume, mean corpuscular Hb (MCH), and platelet count
      were significantly lower in liver cirrhosis group than control group while total
      leukocyte count, neutrophils, and MCH concentration were significantly higher.
      Glucose, total protein, albumin, A/G ratio, and fibrinogen were significantly
      lower, and creatinine, alanine aminotransferase, aspartate aminotransferase,
      alkaline phosphatase, prothrombin time, and APTT were significantly higher than
      the control values. Ultrasound revealed diffuse increase in echogenicity with
      rounded and irregular liver margins. Cytological examination of the ascitic fluid
      and fine-needle aspiration biopsy of liver was not fruitful in the diagnosis of
      liver cirrhosis. CONCLUSIONS: Liver cirrhosis causes clinical and hemo
      biochemical alterations, which require special consideration when treating
      diseased animals. USG, diffuse increase in echogenicity of liver, rounding and
      irregularity of liver margins and microhepatica were the consistent findings. It
      is suggested that USG along with hemo-biochemical alterations may be used as a
      diagnostic tool for liver cirrhosis in dogs.

PMID- 27047121
TI  - Evaluation of lateral flow assay as a field test for investigation of brucellosis
      outbreak in an organized buffalo farm: A pilot study.
AB  - AIM: The aim was to evaluate lateral flow assay (LFA) as a field test for
      investigation of brucellosis outbreak in organized buffalo farm. MATERIALS AND
      METHODS: A total of 153 serum samples were tested to detect the presence of
      brucella antibodies by LFA and three other serological tests i.e. rose bengal
      plate test (RBPT), protein G based indirect enzyme-linked immunoassay (iELISA),
      and competitive ELISA (cELISA). The performances of LFA and other serological
      tests were evaluated using OIE complaint cELISA as the gold standard. RESULTS:
      Serological tests revealed 50% of the animals were seropositive for Brucella
      antibodies and correlated with clinical history of abortions, infertility, and
      productive failures. The newly developed assay showed 87.1% and 92.6% sensitivity
      and specificity, which was even higher than the specificity of RBPT. CONCLUSIONS:
      The investigation proved the potential usefulness of LFA for field diagnosis of
      brucellosis in the regions where laboratory facilities are limited.

PMID- 27047122
TI  - Evaluation of biochemical alterations produced by acetaminophen overdose in
      Bubalus bubalis.
AB  - AIM: Evaluation of the effect of acetaminophen (APAP) overdose on biochemical
      parameters in buffalo calves. MATERIALS AND METHODS: The experiment was conducted
      on six healthy male buffalo calves of 6-12 months age. The APAP was administered
      intramuscularly at the dose rate of 250 mg/kg body weight (B.W.) on day 0,
      followed by two subsequent doses at the dose rate of 50 mg/kg B.W. on day 2 and
      4, respectively. Biochemical parameters including alanine aminotransferase (ALT),
      alkaline phosphatase (ALP), amylase, blood urea nitrogen (BUN), creatinine, and
      total acid phosphate were estimated in the plasma samples collected on 0, 1, 2,
      3, 4, 5, and 6th day from the start of treatment. RESULTS: Significant increase
      in the plasma levels of ALT (446.0%), ALP (137%), BUN (216.8%) and creatinine
      (149.2%) was recorded on day 3, 4, 3, and 4, respectively, after the start of
      APAP dosing. However, a significant decrease was observed in amylase activity
      with a maximum decline of 48.3% on 6th day after the start of treatment. No
      significant alteration was observed in ACP activity after APAP overdose.
      CONCLUSION: Administration of APAP in overdose produced hepatic dysfunction as
      evidenced by a significant increase in the activities of ALT and ALP, whereas
      reduced amylase may indicate acute pancreatitis in buffalo calves. In addition,
      repeated dosing also resulted in renal impairment in these animals as seen by a
      significant elevation in BUN and creatinine levels, whereas negligible effect on
      prostatic function.

PMID- 27047123
TI  - Effect of nutritional status on the ovarian follicular population, yield and
      quality of oocytes in the Ngaoundere Gudali zebu (Bos indicus).
AB  - AIM: The aim of this study was to investigate the effect of nutritional status of
      the Gudali cows slaughtered at the Ngaoundere abattoir on follicular population,
      quality, and oocytes yield. MATERIALS AND METHODS: Blood and ovaries were
      collected from 81 cows aged 6.35+/-0.24 years (3-12 years old), with a body
      condition score (BCS) of 2.93+/-0.09 (1-5). In each ovary, the follicle were
      counted and classified as small (<3 mm), medium (3-8 mm) and large (>8 mm) using
      an electronic caliper. Oocytes were collected by slicing technique and classified
      according to the homogeneity of the cytoplasm and layers of granulosa into four
      groups: I, II, III, and IV. The nutritional status of the animals was determined
      by quantification of serum glucose, total cholesterol, total protein, albumin,
      globulins, urea, and phosphorus level. RESULTS: Of the total 162 ovaries
      harvested, 2916 follicles were counted on the ovarian surface with an average
      population of 36.00+/-2.17 follicles/cow. According to a size distribution,
      16.67+/-1.54 (46.3%), 18.83+/-1.27 (52.3%), and 0.51+/-0.07 (1.4%), respectively
      for small (<3 mm), medium (3-8 mm), and large (>8 mm) were recorded. About 1,929
      oocytes were obtained, with an average recovered of 23.81+/-1.53 oocytes/cow.
      Depending on the quality, 7.79+/-0.55 (32.7%), 6.04+/-0.41 (25.3%), 4.89+/-0.44
      (20.6%), and 5.10+/-0.54 (21.4%) oocytes qualities I, II, III, and IV were
      obtained respectively; with an average cultivable oocyte recovered of 13.83+/
      0.89 (58%). Cows with BCS > 3 and a high albumin and phosphorus level showed a
      highest number of follicles and oocytes able for in vitro maturation. CONCLUSION:
      These results indicated that nutrition remains an important factor for the in
      vitro production of the good embryo and the BCS is a useful tool for the
      selection of females' oocytes donors.

PMID- 27047124
TI  - Pharmacokinetic interaction of curcumin and glibenclamide in diabetic rats.
AB  - AIM: The aim was to assess the pharmacokinetic (PK) interaction of curcumin and
      glibenclamide (GL) in diabetic rats. MATERIALS AND METHODS: Sprague-Dawley rats
      induced with diabetes were divided into 2 groups of six rats in each. Group I: GL
      (6 mg/kg po once daily) treatment in diabetic rats and group 2: Curcumin (50
      mg/Kg po once daily) + GL (dose as above) in diabetic rats. Blood samples were
      collected at pre-determined time intervals for kinetic analysis after the first
      and last oral dosing of GL for single and multiple dose studies, respectively.
      Plasma samples were assayed for GL concentration by high-performance liquid
      chromatography and PK parameters were analyzed. RESULTS: The half-life (t1/2) and
      mean residence time (MRT) of GL were significantly increased in curcumin pre
      treated rats as compared to GL alone in single and multiple dose studies.
      Similarly, the Vdss was significantly increased in curcumin pre-treated rats in
      single dose study as compared to GL alone treated group, but no significant
      difference was observed in multiple dose kinetics. CONCLUSION: The study revealed
      higher values (t1/2, MRT and Vdss) of GL in curcumin pre-treated group due to the
      inhibitory effect of curcumin on intestinal CYP3A4.

PMID- 27047125
TI  - Hemato-biochemical and hormonal profiles in post-partum water buffaloes (Bubalus
      bubalis).
AB  - AIM: The objective of the present study was to compare serum as well as
      follicular fluid (FF) biochemical and hormonal profiles along with hematological
      parameters in postpartum estrus, anestrus, and cystic buffaloes. MATERIALS AND
      METHODS: Postpartum buffaloes were selected in three different groups (within 40
      60 days of parturition at estrus-Group-I, postpartum >90 days at anestrum-Group
      II, and postpartum cystic buffaloes in Group III). The animals selected were
      examined for follicular wave dynamics by routine trans-rectal ultrasonography and
      FF was collected by transvaginal ultrasound-guided ovum pick up technique. All
      hematological and biochemical parameters were analyzed by automatic analyzers
      while hormonal profiles analyzed by commercially available ELISA kits. RESULTS:
      In the present investigation, estrum and anestrum animal differ significantly in
      hemoglobin levels. Serum estradiol differs significantly in estrus and anestrus
      while no significant difference in progesterone concentration was noted among all
      three stages. The results of our study suggest that significant higher increase
      in total protein (TP), calcium and glucose values in estrum while urea, aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase significantly
      higher in anestrum animals. CONCLUSION: The conclusion of the present study is
      that TP and albumin, calcium, urea, glucose affects oocyte development and
      quality.

PMID- 27047126
TI  - Optimizing age of bull at first use in relation to fertility of Murrah breeding
      bulls.
AB  - AIM: The aim of the present investigation was to optimize the age at first use
      (AAFU) of semen of Murrah breeding bulls, which will help in early selection of
      bulls under progeny testing program for improving the reproductive performance in
      the herd. MATERIALS AND METHODS: The data on AAFU, conception rate based on first
      A.I. (CRFAI), overall conception rate (OCR), and birth weight (B.WT) of 57 Murrah
      bulls during 1993-2014 at NDRI center pertaining to 14 sets of Network Project on
      Buffalo Improvement at ICAR-National Dairy Research Institute, Karnal, Haryana,
      India were adjusted for significant environmental influences and subsequently
      analyzed. Simple and multiple regression models were used for prediction of CRFAI
      and OCR of Murrah breeding bulls. Comparative evaluation of three developed
      models (I-III) showed that Model III, having AAFU and B.WT, fulfill the accuracy
      of model as revealed by high coefficient of determination, low mean sum of
      squares due to error, low conceptual predictive value, and low Bayesian
      information criterion. RESULTS: The results revealed that the average predicted
      CRFAI was highest (39.95%) at <3.5 years and lowest (34.87%) at >4.5 years of age
      at first A.I/use. Similarly, average predicted OCR was highest (41.05%) at <3.5
      years and lowest (39.42%) at >4.5 years of age at first A.I/use of Murrah bulls.
      CONCLUSION: In organized herd under progeny testing program, Murrah bulls should
      be used at young age, i.e. prior to 3.5 years, which is expected to result in
      5.08% better CRFAI and 1.63% better OCR in comparison to Murrah bulls used after
      4.5 years of age.

PMID- 27047127
TI  - Utility of a rapid immunochromatographic strip test in detecting canine
      parvovirus infection compared with polymerase chain reaction.
AB  - AIM: The present study was undertaken to detect the presence of canine parvovirus
      (CPV) in fecal samples of diarrheic dogs by conventional polymerase chain
      reaction (PCR) and immunochromatographic (IC) strip test and to compare the
      diagnostic potential of these tests. MATERIALS AND METHODS: A total of 50 fecal
      samples collected from diarrheic dogs suspected for CPV infection were subjected
      to PCR using CPV-555 primer amplifying the gene coding for the VP1 protein. These
      samples were also tested by IC strip test using a commercial rapid Ag test kit.
      The results were statistically analyzed using McNemar test. RESULTS: A total of
      22 samples (44%) were detected as positive by PCR, which yielded a specific
      amplicon of 583 bp. In IC strip test, 18 (36%) samples were found to be positive.
      The sensitivity of the test as compared to PCR was found to be 72.22% and
      specificity was 92.86%. Positive predictive value and negative predictive value
      of IC strip test was found to be 88.89% and 81.25%, respectively. Statistical
      analysis of the results of PCR and IC assay using McNemar test revealed no
      significant difference (p>0.05). CONCLUSION: The IC strip test could be employed
      as a rapid field level diagnostic tool for the diagnosis of canine parvoviral
      diarrhea.

PMID- 27047128
TI  - Genetic characterization of Gaddi goat breed of Western Himalayas using
      microsatellite markers.
AB  - AIM: In the present study, genetic characterization of Gaddi goat breed, a native
      to north temperate western Himalayan region of India, was carried out for the
      purpose of breed characterization and assessing existing intra-population genetic
      diversity. MATERIALS AND METHODS: Totally, 75 blood samples procured at random
      from genetically unrelated animals of two sexes and different age groups and true
      to breed type were collected from different locations in the breeding tract of
      these goats in Himachal Pradesh, of which only 51 samples with desired quantity
      and quality were subjected to further processing for DNA isolation. The multi
      locus genotype data were generated on 51 Gaddi goats sampled across different
      regions of the breeding tract in Himachal Pradesh using 15 FAO recommended goat
      specific microsatellite markers, which gave amplification and observed and
      effective number of alleles, gene frequency, observed and expected heterozygosity
      were estimated through PopGene software (1.3.1). RESULTS: A total of 135 distinct
      alleles were observed with mean observed and effective number of alleles as
      9.0000+/-0.82 and 6.5874+/-0.56 respectively across all 15 studied loci. The
      maximum (15) alleles were contributed by loci DRBP1 and P19/DYA and the least (5)
      by SRCRSP5. The mean heterozygosity was observed to be 0.8347+/-0.01 ranging from
      0.7584 (SRCRSP5) to 0.9156 (P19-DYA) across all loci. The mean observed (HO) and
      expected (HE) heterozygosities across all loci were 0.7484+/-0.02 and 0.8431+/
      0.01 respectively. The polymorphism information content (PIC) value ranged from
      0.7148 (SRCPS5) to 0.909 (P19-DYA) with mean PIC of 0.8105+/-0.01 in the present
      study. The average heterozygosity was observed to be 0.8347+/-0.01 ranging from
      0.7584 (SRCRSP5) to 0.9156 P19 (DYA) across all loci. CONCLUSION: Microsatellite
      analysis revealed high level of polymorphism across studied microsatellite
      markers and informativeness of the markers for genetic diversity analysis studies
      in Gaddi goats. This high level of polymorphism can be utilized to plan future
      association studies to exploit the uniqueness and adaptability of indigenous
      Gaddi goat breed of Western Himalayas. Most studied microsatellite markers had
      desired neutrality, thus proving to be good candidates for genetic
      characterization and diversity analysis in Gaddi breed of goats also.

PMID- 27047129
TI  - Single nucleotide markers of D-loop for identification of Indian wild pig (Sus
      scrofa cristatus).
AB  - AIM: Partial fragment of D-loop region extending from 35 to 770 were compared
      with corresponding sequences of 16 wild pigs and 9 domestic pig breeds from
      different parts of the world for detection of single nucleotide polymorphism
      (SNP) markers in the region. The paper also reappraises SNP markers from two
      fragments of cytochrome b gene and a fragment 12S rRNA gene distinguishing the
      Indian wild pig from other pig species of the world. MATERIALS AND METHODS:
      Deoxyribonucleic acid (DNA) was isolated from 14 and 12 tissue samples of Indian
      wild and domestic pigs, respectively, collected from Central India for
      characterization of the D-loop DNA sequences using universal primers. The
      sequences obtained were aligned along with the retrieved sequences to analyze
      species-specific SNP marker. RESULTS: A total of 58 mitochondrial D-loop gene
      sequences of pig races were aligned to identify 1349 polymorphic sites in the
      fragment from nucleotide positions 35-770 bp and four SNP markers were identified
      to differentiate Indian wild pig from all the sequences investigated in this
      study. With the inclusion of cytochrome b gene and 12S rRNA gene fragments, the
      present study contributes to the total 15 SNP markers, which have been identified
      in the mitochondrial fragment of 1936 bp for identification of Indian wild pig.
      CONCLUSION: SNP markers have advantages over other marker types and do not
      require subsequent standardization to compare data across studies or
      laboratories.

PMID- 27047130
TI  - Hepatoprotective activity of Moringa oleifera against cadmium toxicity in rats.
AB  - AIM: The present investigation has been conducted to evaluate the
      hepatoprotective activity of Moringa oleifera against cadmium-induced toxicity in
      rats. MATERIALS AND METHODS: For this study, 18 Wistar albino rats were taken.
      Control group, Group I rats were given cadmium chloride @ 200 ppm per kg and
      Group II rats were treated with M. oleifera extract @ 500 mg/kg along with
      cadmium chloride @ 200 ppm per kg (daily oral for 28 days). On 29(th) day,
      animals were slaughtered and various parameters were determined. Serum
      biomarkers, oxidative stress parameters, histomorphological examination were
      carried out with estimation of cadmium concentration in liver tissues. RESULTS:
      Oral administration of cadmium chloride @ 200 ppm/kg for 28 days resulted in a
      significant increase in aspartate aminotransferase (AST), alanine transaminase
      (ALT), alkaline phosphatase (ALP), significant (p<=0.01) increase of lipid
      peroxidation (LPO) and decrease in superoxide dismutase (SOD), and increase in
      cadmium accumulation in liver. Treatment with M. oleifera @ 500 mg/kg
      significantly (p<0.01) decreased the elevated ALP, AST, ALT, LPO levels and
      increase in SOD levels, and as compared to cadmium chloride treated group.
      However, there was no significant difference in cadmium concentration in liver
      when compared with cadmium chloride treated group. CONCLUSION: The study conclude
      that supplementation of M. oleifera (500 mg/kg), daily oral for 28 days has shown
      protection against cadmium-induced hepatotoxicity.

PMID- 27047131
TI  - Prevalence of classical swine fever in Karnataka, India.
AB  - AIM: The present study was conducted to know the current scenario of classical
      swine fever (CSF) in Bengaluru Urban, Bengaluru Rural, Chikkaballapur, Madikeri,
      Mandya, Bagalkot, Gadag, Yadgir, Koppal, and Bidar districts of Karnataka with
      the using of both antigen and antibody ELISA. MATERIALS AND METHODS: We collected
      218 sera and 121 blood samples from pigs from 10 different districts of
      Karnataka. Screening of sera for CSF IgG antibody and whole blood for CSF virus
      antigen were carried out using the CSF virus (CSFV) antibody and antigen ELISA
      kits, respectively. RESULTS: The mean seroprevalence was 41% (89/218) and
      prevalence of CSFV antigen in blood samples was 32% (39/121) for the 10 districts
      of Karnataka. Seroprevalence of 61%, 29%, 20%, and 21%; and antigen prevalence of
      40%, 50%, 13%, and 12% were recorded for Bangalore, Mysore, Belgaum, and Gulbarga
      divisions of Karnataka, respectively. CONCLUSIONS: The study revealed an
      alarmingly high prevalence of CSF, both for the antigen (32%) and antibody (41%)
      in Karnataka. Southern Karnataka has the highest seroprevalence (61% in Bangalore
      and 29% in Mysore divisions), which confirms the endemicity of the disease in
      that region. This could be attributed to the intensive pig farming practices in
      the region as compared to Northern Karnataka (Seroprevalence of 20% in Belgaum
      and 21% in Gulbarga divisions), where the commercial pig farming is still in
      infantile stages.

PMID- 27047132
TI  - Organochlorine and organophosphorus pesticide residues in fodder and milk samples
      along Musi river belt, India.
AB  - AIM: The present study was conducted to find the organochlorine pesticide (OCP)
      and organophosphorus pesticide (OPP) residues in fodder and milk samples along
      Musi river belt, India. MATERIALS AND METHODS: Fodder and milk samples collected
      from the six zones of Musi river belt, Hyderabad India were analyzed by gas
      chromatography with electron capture detector for OCP residues and pulsated flame
      photometric detector for the presence of OPP residues. RESULTS: The gas
      chromatographic analysis of fodder samples of Zone 5 of Musi river showed the
      residues of dicofol at concentration of 0.07+/-0.0007 (0.071-0.077). Among
      organophosphorus compounds, dimetheoate was present in milk samples collected
      from Zone 6 at a level of 0.13+/-0.006 (0.111-0.167). The residues of OCPs, OPPs
      and cyclodies were below the detection limit in the remaining fodder and milk
      samples collected from Musi river belt in the present study. CONCLUSION: The
      results indicate that the pesticide residues in fodder and milk samples were well
      below the maximum residue level (MRL) values, whereas dicofol in fodder and
      dimethoate in milk were slightly above the MRL values specified by EU and CODEX.

PMID- 27047133
TI  - Effect of varying levels of formaldehyde treatment of mustard oil cake on rumen
      fermentation, digestibility in wheat straw based total mixed diets in vitro.
AB  - AIM: The aim of the current study was to protect the protein in mustard cake by
      different levels of formaldehyde treatment with a view to optimize the level of
      formaldehyde. MATERIALS AND METHODS: Different levels of formaldehyde treatment
      (0, 1, 1.5 and 2% of crude protein) containing concentrate and roughages diet in
      40:60 ratio were tested for their effect on nutrients digestibility, in vitro
      ammonia release, in vitro gas production and change in protein fractions. Non
      significant (p<=0.05) effect on pH, microbial biomass, partitioning factor, total
      gas production (TGP), TGP per g dry matter and TGP per g digestible dry matter
      (ml/g) was observed in almost all the treatments. RESULTS: Total volatile fatty
      acids at 2% formaldehyde treatment level of mustard cake was lower (p<0.05) as
      compared to other groups, while in vitro dry matter digestibility and in vitro
      organic matter digestibility were reported to be low in 1% formaldehyde treated
      group. CONCLUSION: On a holistic view, it could be considered that formaldehyde
      treatment at 1.5% level was optimal for protection of mustard oil cake protein.

PMID- 27047134
TI  - Evaluation of Yucca schidigera extract as feed additive on performance of broiler
      chicks in winter season.
AB  - AIM: Yucca schidigera extract has been successfully used as feed additives in the
      poultry industry. It enhances the growth and productivity in broiler production.
      Hence, the present study was designed to analyze the effect of Y. schidigera
      extract in growth, carcass quality and behavior along with its economical utility
      in broiler rearing. MATERIALS AND METHODS: Total, 120 numbers of day-old broiler
      chicks of equal sex ratio were randomly divided into Yucca supplemented treatment
      and control group, each having 60 birds in three replications of 20 numbers. The
      feeding management and rearing conditions were similar for all the groups as per
      the standard except the Yucca supplementation in the treatment group @ 125 mg/kg
      of feed. The parameters with respect to growth, carcass, behavior, and litter
      content were recorded as per standard procedures. RESULTS: The Yucca
      supplementation can effectively enhance growth of 173 g in 6(th) week by
      utilizing lesser feed intake than control group, which ultimately proves better
      feed conversion rate, protein efficiency ratio, and energy efficiency ratio in
      broiler production. Eviscerated weight of 58.50% for the treatment group was
      significantly higher (p<0.05) than 54.10% in the control group. The breast meat
      yield of Yucca group (32.23%) was significantly higher (p<0.05) than control
      (30.33%). More frequency of agonistic behavioral expressions was noticed in the
      control group than the treatment group. A profit of 43.68% was received by usage
      of Yucca supplementation in the diet on live weight basis. Numerically, lower
      percentage of moisture was present in Yucca treated group than the control.
      CONCLUSION: From this study, it can be concluded that Yucca supplementation has
      an important role in augmenting broiler's growth performance, efficiency to
      utilize feed, protein and energy, and survivability. Hence, use of Yucca powder
      in broiler ration could be beneficial to maintain the litter quality, which
      directly enhances the productivity in broiler production without any adverse
      effect.

PMID- 27047135
TI  - Seroprevalence and comparison of different serological tests for brucellosis
      detection in small ruminants.
AB  - AIM: The aim was to study the seroprevalence and efficacy of the different
      serological tests used for detection of antibody against Brucella species in
      small ruminants of Banaskantha district of North-Gujarat. MATERIALS AND METHODS:
      Total 1000 serum samples comprising of 485 from sheep and 515 from goat tested
      for detection of antibodies against the Brucella species by three different
      serological tests viz., Rose bengal plate test (RBPT), Standard tube
      agglutination test (STAT), and Indirect Enzyme-linked immunosorbent assay (I
      ELISA). RESULTS: The seroprevalence of brucellosis in small ruminants was 11.30%,
      11.10%, and 8.80% by RBPT, STAT, and I-ELISA, respectively. The seroprevalence of
      brucellosis was found to be higher in sheep than goats. The sensitivity of RBPT
      was found slight more than STAT, but the specificity of both tests was same. In
      this study, the overall agreement of RBPT and STAT with I-ELISA was found 92.50%
      and 92.30% in small ruminants, respectively. CONCLUSION: I-ELISA was a better
      serological test as compared to RBPT and STAT in the sense of sensitivity,
      specificity, and rapidity and it could be advocated for screening of brucellosis
      in sheep and goats.

PMID- 27047136
TI  - Phylogenetic analysis of Dichelobacter nodosus serogroup-specific fimA gene from
      ovine footrot in Andhra Pradesh.
AB  - AIM: Identification of different serogroups of Dichelobacter nodosus prevailing
      in the region and to understand the degree of genetic heterogeneities among the
      different isolates of D. nodosus. MATERIALS AND METHODS: A total of 150 exudate
      samples of footrot lesions with a lesion score of 2-4 were collected from
      naturally infected sheep. The samples were screened by polymerase chain reaction
      (PCR) targeting D. nodosus specific 16srRNA. Of 150 samples screened, 70 samples
      were found to be positive. The positive samples were attempted for isolation of
      D. nodosus, out of which 16 isolates were recovered. All the isolates were
      subjected to serogrouping by multiplex PCR targeting fimA gene using A-I
      serogroup specific primers. RESULTS: Of 16 isolates, 7 (43.75%) isolates were
      serogroup B, 4 (25.00%) isolates were serogroup A, 3 isolates (18.75%) were
      serogroup I and 2 (12.5%) isolates yielded both serogroup A and B. phylogenetic
      analysis was performed using neighbor-joining algorithm of the ClustelX2 software
      in order to study whether the serogroups isolated in the present investigation
      differed genetically from other published serogroups. The fimA gene sequence of
      present isolates of serogroups A, B, and I were segregated into three distinct
      groups with high bootstrap values. The serogroup B clustered with Australian
      isolate of serotype B1 suggesting high genetic similarity of the present isolate
      with serotype B1. CONCLUSIONS: The clinical samples were collected from suspected
      outbreaks of footrot and identified the prevalence of D. nodosus by PCR targeting
      16srRNA gene. Identified serogroups A, B, and I from different districts of
      Andhra Pradesh. The phylogenetic analysis will help for the tentative
      identification of serotypes present in the serogroup and to understand the degree
      of genetic heterogeneities among the different isolates of D. nodosus.

PMID- 27047137
TI  - Effect of tanniferous leaf meal based multi-nutrient blocks on feed intake,
      hematological profile, immune response, and body weight changes in Haemonchus
      contortus infected goats.
AB  - AIM: The aim was to assess the effect of multi nutrient block (MNB)
      supplementation with and without tanniferous leaf meal mixture on feed intake,
      hematological profile, immune response, and body weight changes of goats that
      were experimentally infected with Haemonchus contortus. MATERIALS AND METHODS:
      Total 12 adult male goats of similar age and body weight (26.49+/-0.87) were
      allocated in 3 groups in completely randomized design. MNB supplemented in first
      two groups i.e. in T1 (no infection) and T2 (H. contortus infection @ 1500
      L3/goat) group, while, MNB-condensed tannin (CT) supplemented in T3 (H. contortus
      infection @ 1500 L3/goat + CT source). All goats were fed concentrate mixture @
      100 g/day/goat, ad lib wheat straw and MNB or MNB-CT to meet their requirement
      for maintenance. Body weights were recorded and blood and fecal samples were
      collected at 0 day and thereafter at 15 days intervals for a period of 75 days
      for the assessment of body weight changes, hematological profile and H. contortus
      loads. Both humoral and cell-mediated immune (CMI) response were assessed at the
      end of feeding trial. RESULTS: Mean hemoglobin and packed cell volume (PCV)
      levels were found to be highest (p<0.001, p<0.05) in T1 group followed by T3
      group and lowest values were observed in T2 group. However, The PCV values
      between T1 and T3 groups were found to be statistically non-significant (p<0.05).
      The humoral and CMI response were significantly (p<0.036) higher in T3 group as
      compared to T2 group. MNB-CT supplementation significantly (p<0.001) reduced
      fecal egg counts in T3 group as compared to MNB supplemented T2 group.
      CONCLUSION: Supplementation of MNB-CT could be used as an alternative sustainable
      method to control H. contortus and maintained health status and performance of
      goats in face of parasitic challenge.

PMID- 27047138
TI  - Influenza A plasma and serum virus antibody detection comparison in dogs using
      blocking enzyme-linked immunosorbent assay.
AB  - BACKGROUND AND AIM: The influenza A virus (IAV) is an important zoonotic pathogen
      with infections also reported in dogs. IAV infections can be detected through the
      presence of antibodies using the enzyme-linked immunosorbent assay (ELISA). Serum
      is the only standard sample source; however, there is no information on the
      availability of other sample sources for IAV antibody detection in dogs. Compared
      with serum, plasma is more widely employed in most animal hospitals. The object
      of this study is to investigate whether plasma collected in
      ethylenediaminetetraacetic acid (EDTA) tubes (EDTA plasma) or heparin tubes
      (heparin plasma) could be used in the ELISA protocol instead of serum for IAV
      antibody detection in dogs. MATERIALS AND METHODS: Totally, 82 matched EDTA
      plasma and serum sample pairs and 79 matched heparin plasma and serum sample
      pairs were employed using blocking enzyme-linked immunosorbent assay (bELISA).
      The agreement and correlation between the plasma (EDTA or heparin plasma) and
      serum were assessed using the agreement index kappa (kD) calculation and Pearson
      correlation coefficient, respectively. RESULTS: The agreement index kD of EDTA
      plasma and serum was 1.0, and that of heparin plasma and serum was 0.85. The
      Pearson correlation coefficient of EDTA plasma and serum was 0.87 (p<0.01), and
      that of heparin plasma and serum was 0.82 (p<0.01). CONCLUSION: The results
      proved that plasma, especially EDTA plasma, could be substituted for serum in the
      bELISA test. This might greatly expand the clinical applicability of IAV antibody
      detection in dogs.

PMID- 27047139
TI  - Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in
      rodents.
AB  - AIM: The present study was performed to investigate acute and subchronic oral
      toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. MATERIALS
      AND METHODS: Acute oral administration of F. assa-foetida was done as a single
      bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was
      done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague
      Dawley rats. RESULTS: The obtained data revealed that oral administration of F.
      assa-foetida extract in rats for 28 successive days had no significant changes on
      body weight, body weight gain, the hematological parameters in rats all over the
      period of the experiment, and there are no significant increases in the activity
      of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,
      creatinine and urea. Liver of treated rats showed mild changes as thrombosis and
      sinusoidal leukocytosis. It also showed portal infiltration with inflammatory
      cells, while kidney of treated rat showed an atrophy of glomerular tuft,
      thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It
      also showed dilatation and congestion of renal blood vessels. CONCLUSION: We
      concluded that F. assa-foetida gum had broad safety and little toxicity for short
      term use in dose of 250 mg/kg.

PMID- 27047140
TI  - Role of parasitic vaccines in integrated control of parasitic diseases in
      livestock.
AB  - Parasitic infections adversely affect animal's health and threaten profitable
      animal production, thus affecting the economy of our country. These infections
      also play a major role in the spread of zoonotic diseases. Parasitic infections
      cause severe morbidity and mortality in animals especially those affecting the
      gastrointestinal system and thus affect the economy of livestock owner by
      decreasing the ability of the farmer to produce economically useful animal
      products. Due to all these reasons proper control of parasitic infection is
      critically important for sustained animal production. The most common and
      regularly used method to control parasitic infection is chemotherapy, which is
      very effective but has several disadvantages like drug resistance and drug
      residues. Integrated approaches to control parasitic infections should be
      formulated including grazing management, biological control, genetic resistance
      of hosts, and parasitic vaccines. India ranks first in cattle and buffalo
      population, but the majority of livestock owners have fewer herds, so other
      measures like grazing management, biological control, genetic resistance of hosts
      are not much practical to use. The most sustainable and economical approach to
      control parasitic infection in our country is to vaccinate animals, although
      vaccines increase the initial cost, but the immunity offered by the vaccine are
      long lived. Thus, vaccination of animals for various clinical, chronic,
      subclinical parasitic infections will be a cheaper and effective alternative to
      control parasitic infection for long time and improve animal production. 

PMID- 27047141
TI  - Detection and characterization of extended-spectrum beta-lactamases (blaCTX-M-1
      and blaSHV ) producing Escherichia coli, Salmonella spp. and Klebsiella
      pneumoniae isolated from humans in Mizoram.
AB  - AIM: The present study was conducted to isolate and characterize the extended
      spectrum beta-lactamases (ESBLs) producing enteric bacteria in human beings in
      Mizoram, India. MATERIALS AND METHODS: Fecal samples were collected from human
      beings with or without the history of diarrhea from different hospitals of
      Mizoram. Samples were processed for isolation and identification of Escherichia
      coli, Salmonella and Klebsiella pneumoniae. All the isolates were subjected to
      antibiotic sensitivity assays. Phenotypically, ESBLs production ability was
      determined by double discs synergy test (DDST) method. ESBLs producing isolates
      were subjected to polymerase chain reaction (PCR) for detection of ESBLs genes.
      Plasmids were cured by acridine orange. Transfer of resistance from a donor to
      recipient strains was done by in vitro horizontal method. RESULTS: A total of 414
      enteric bacteria were isolated from 180 fecal samples (113 were from diarrheic
      patients and 67 were from non-diarrheic patients), of which 333 (80.44%), 52
      (12.56%), and 29 (7.00%) were E. coli, K. pneumoniae and Salmonella spp.,
      respectively. Double discs synergy test (DDST) exhibited 72 (21.62%) E. coli, 12
      (23.08%) K. pneumoniae and 4 (13.79%) Salmonella spp. were ESBLs producers.
      Altogether, 24 (13.04%) isolates were found to be positive for at least one
      resistance genes under this study. A total of 36 (8.70%) E. coli, 4 (0.97%) K.
      pneumoniae and 2 (0.48%) Salmonella spp. were found to be positive for blaCTX-M-1
      gene by PCR. Similarly, 5 (1.21%) E. coli and 4 (0.97%) K. pneumoniae isolates
      were found to be positive for blaSHV gene. A total of 3 (0.72%) K. pneumoniae
      isolates were recorded as positive for both blaCTX-M-1 and blaSHV genes. All the
      isolates were carrying plasmids ranging between 0.9 kb and ~30 kb. The resistance
      plasmid could not be transferred to a recipient by in vitro horizontal gene
      transfer method. CONCLUSION: ESBLs producing enteric bacteria are circulating in
      human population in North Eastern Region of India. Indiscriminate use of
      antibiotics should be avoided to control the menace of multidrug resistance
      bacteria in the environment, animals, and human beings.

PMID- 27047142
TI  - Evaluation of various feedstuffs of ruminants in terms of chemical composition
      and metabolisable energy content.
AB  - AIM: The aim was to determine the chemical composition and metabolisable energy
      (ME) content of feedstuffs used in ruminant animals using in vitro method.
      MATERIALS AND METHODS: A total of 18 feedstuffs used for ruminant feeding
      including cultivated non-leguminous fodders like maize, sorghum, pearl millet,
      and oat; leguminous fodders like cowpea and berseem; agro-industrial by-products
      such as wheat bran, deoiled rice bran, rice polish, wheat straw, and concentrates
      such as mustard oil cake, groundnut cake, soybean meal, cotton seed cake, grains
      like maize, oat, wheat, and barley were taken for this study. Chemical
      compositions and cell wall constituents of test feeds were determined in
      triplicate. The crude protein (CP) content was calculated as nitrogen (N) * 6.25.
      True dry matter digestibility (TDMD), true organic matter digestibility (TOMD),
      ME, and partitioning factor (PF) values were determined by in vitro gas
      production technique (IVGPT). RESULTS: The CP content of non-leguminous fodders
      varied from 7.29% (sorghum) to 9.51% (maize), but leguminous fodders had less
      variation in CP. Oilseed cakes/meals had high CP and ether extract (EE) content
      than other feedstuffs except rice polish, which had 12.80% EE. Wheat straw
      contained highest fiber fractions than the other ingredients. ME content was
      highest in grains (wheat-12.02 MJ/kg) and lowest in wheat straw (4.65 MJ/kg) and
      other roughages. TDMD of grains and oilseed cakes/meals were higher than the
      fodders and agro-industrial by-products. The same trend was observed for TOMD.
      CONCLUSIONS: It was concluded that the energy feeds showed a great variation in
      chemical composition and ME content. The results of this study demonstrated that
      the kinetics of gas production of energy feed sources differed among themselves.
      Evaluation of various feedstuffs is helpful in balanced ration formulation for
      field animals and under farm conditions for better utilization of these commonly
      available feed resources.

PMID- 27047143
TI  - Cloning and sequencing of hfq (host factor required for synthesis of
      bacteriophage Q beta RNA) gene of Salmonella Typhimurium isolated from poultry.
AB  - AIM: The aim was to clone and sequence hfq gene of Salmonella Typhimurium strain
      PM-45 and compare its sequence with hfq gene of other serovar of Salmonella.
      MATERIALS AND METHODS: Salmonella Typhimurium strain PM-45 was procured from the
      G. B. Pant University of Agriculture and Technology, Pantnagar, India. The
      genomic DNA was isolated from Salmonella Typhimurium. Hfq gene was polymerase
      chain reaction (PCR) amplified from the DNA using specific primers, which was
      subsequently cloned into pET32a vector and transformed into Escherichia coli BL21
      pLys cells. The recombinant plasmid was isolated and subjected to restriction
      enzyme digestion as well as PCR. The clone was then sequenced. The sequence was
      analyzed and submitted in GenBank. RESULTS: PCR produced an amplicon of 309 bp.
      Restriction digestion of the recombinant plasmid released the desired insert. The
      hfq sequence shows 100% homology with similar sequences from other Salmonella
      Typhimurium isolates. Both nucleotide and amino acid sequences are highly
      conserved. The submitted sequence is having Genbank accession no KM998764.
      CONCLUSION: Hfq, the hexameric RNA binding protein is one of the most important
      post-transcriptional regulator of bacteria. The sequence of hfq gene of
      Salmonella Typhimurium is highly conserved within and between Salmonella enterica
      serovars. This gene sequence is probably under heavy selection pressure to
      maintain the conformational integrity of its product in spite of its being not a
      survival gene.

PMID- 27047144
TI  - Genetic polymorphism of toll-like receptors 4 gene by polymerase chain reaction
      restriction fragment length polymorphisms, polymerase chain reaction-single
      strand conformational polymorphism to correlate with mastitic cows.
AB  - AIM: An attempt has been made to study the toll-like receptors 4 (TLR4) gene
      polymorphism from cattle DNA to correlate with mastitis cows. MATERIALS AND
      METHODS: In present investigation, two fragments of TLR4 gene named T4CRBR1 and
      T4CRBR2 of a 316 bp and 382 bp were amplified by polymerase chain reaction (PCR),
      respectively from Kankrej (22) and Triple cross (24) cattle. The genetic
      polymorphisms in the two populations were detected by a single-strand
      conformational polymorphism in the first locus and by digesting the fragments
      with restriction endonuclease Alu I in the second one. RESULTS: Results showed
      that both alleles (A and B) of two loci were found in all the two populations and
      the value of polymorphism information content indicated that these were highly
      polymorphic. Statistical results of chi(2) test indicated that two polymorphism
      sites in the two populations fit with Hardy-Weinberg equilibrium (p<0.05).
      Meanwhile, the effect of polymorphism of TLR4 gene on the somatic cell score
      (SCS) indicated the cattle with allele a in T4CRBR1 showed lower SCS than that of
      allele B (p<0.05). Thus, the allele A might play an important role in mastitis
      resistance in cows. CONCLUSION: The relationship between the bovine mastitis
      trait and the polymorphism of TLR4 gene indicated that the bovine TLR4 gene may
      play an important role in mastitis resistance.

PMID- 27047145
TI  - Isolation and purification of beta-lactoglobulin from cow milk.
AB  - AIM: The present study was undertaken to standardize a convenient method for
      isolation and purification of beta-lactoglobulin (beta-lg) from cow milk keeping
      its antigenicity intact, so that the purified beta-lg can be used for detection
      of cow milk protein intolerance (CMPI). MATERIALS AND METHODS: Raw milk was
      collected from Gir breed of cattle reared in Haringhata Farm, West Bengal. Milk
      was then converted to skimmed milk by removing fat globules and casein protein
      was removed by acidification to pH 4.6 by adding 3 M HCl. beta-lg was isolated by
      gel filtration chromatography using Sephacryl S-200 from the supernatant whey
      protein fraction. Further, beta-lg was purified by anion-exchange chromatography
      in diethylaminoethyl-sepharose. Molecular weight of the purified cattle beta-lg
      was determined by 15 percent one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and was analyzed by gel documentation system
      using standard molecular weight marker. RESULTS: The molecular weight of the
      purified cattle beta-lg was detected as 17.44 kDa. The isolated beta-lg was
      almost in pure form as the molecular weight of purified beta-lg monomer is 18kDa.
      CONCLUSION: The study revealed a simple and suitable method for isolation of beta
      lg from whey protein in pure form which may be used for detection of CMPI.

PMID- 27047146
TI  - Serum metabolic and minerals profile in norgestomet primed postpartum anestrous
      surti buffaloes.
AB  - AIM: The study was undertaken to find out the serum metabolic and minerals
      profile in postpartum anestrous surti buffaloes treated with norgestomet ear
      implants alone and in combination with pregnant mare serum gonadotropin (PMSG).
      MATERIALS AND METHODS: The study was conducted on 18 postpartum anestrous Surti
      buffaloes divided into three groups of six animals each at random to conduct the
      experiment. The buffaloes in Group-I and Group-II were implanted with Crestar ear
      implant for 9 days together with 2 ml injection of Crestar solution given i/m on
      the day of the implant insertion. In Group-II, additionally 500 IU PMSG was given
      i/m on the day of implant removal, whereas the buffaloes in Group-III served as
      anestrous control group and received 5 ml Normal Saline i/m on day 0 and 9 as a
      placebo treatment. RESULTS: The overall serum total protein values did not differ
      significantly (p > 0.05) between time (days) intervals in any of the groups. The
      mean serum total cholesterol levels at 10(th) day and on the day of estrus were
      found significantly lower (p < 0.05) in the control group as compared to
      treatment Groups I and II. However, there was no significant difference (p >
      0.05) at 10(th) day and on the day of estrus between treatment groups (T1 and
      T2). The overall mean serum cobalt, zinc, iron, and manganese values did not
      differ significantly (p > 0.05) between different time intervals among any of the
      groups, except copper which was significantly lower (p < 0.05) at 10(th) day in
      control group as compared to treatment groups. CONCLUSION: Microelements cannot
      be synthesized in the body. Hence, it is concluded that the mineral mixture
      should be supplied daily in the animals ration to suffice the requirement of the
      trace elements. The mean serum metabolic and micro-minerals profiles in treatment
      and control groups revealed that overall mean serum total protein, cholesterol,
      copper, and zinc levels were apparently higher in treatment groups whereas, mean
      serum cobalt, iron, and manganese concentration had no consistent trend between
      treatment and control groups of Surti buffaloes.

PMID- 27047147
TI  - Critical sources of bacterial contamination and adoption of standard sanitary
      protocol during semen collection and processing in Semen Station.
AB  - AIM: The present investigation was conducted to locate the critical sources of
      bacterial contamination and to evaluate the standard sanitation protocol so as to
      improve the hygienic conditions during collection, evaluation, and processing of
      bull semen in the Semen Station. MATERIALS AND METHODS: The study compared two
      different hygienic procedures during the collection, evaluation and processing of
      semen in Central Semen Station, Anjora, Durg. Routinely used materials including
      artificial vagina (AV) inner liner, cone, semen collection tube, buffer,
      extender/diluter, straws; and the laboratory environment like processing lab,
      pass box and laminar air flow (LAF) cabinet of extender preparation lab,
      processing lab, sealing filling machine, and bacteriological lab were subjected
      to bacteriological examination in two phases of study using two different
      sanitary protocols. Bacterial load in above items/environment was measured using
      standard plate count method and expressed as colony forming unit (CFU). RESULTS:
      Bacterial load in a laboratory environment and AV equipments during two different
      sanitary protocol in present investigation differed highly significantly
      (p<0.001). Potential sources of bacterial contamination during semen collection
      and processing included laboratory environment like processing lab, pass box, and
      LAF cabinets; AV equipments, including AV Liner and cone. Bacterial load was
      reduced highly significantly (p<0.001) in AV liner (from 2.33+/-0.67 to 0.50+/
      0.52), cone (from 4.16+/-1.20 to 1.91+/-0.55), and extender (from 1.33+/-0.38 to
      0) after application of improved practices of packaging, handling, and
      sterilization in Phase II of study. Glasswares, buffers, and straws showed nil
      bacterial contamination in both the phases of study. With slight modification in
      fumigation protocol (formalin @600 ml/1000 ft(3)), bacterial load was
      significantly decreased (p<0.001) up to 0-6 CFU in processing lab (from 6.43+/
      1.34 to 2.86+/-0.59), pass box (from 12.13+/-2.53 to 3.78+/-0.79), and nil
      bacterial load was reported in LAFs. CONCLUSION: Appropriate and careful
      management considering critical points step by step starting right from
      collection of semen to their processing can significantly minimize bacterial
      contamination.

PMID- 27047148
TI  - Co-culture: A quick approach for isolation of street rabies virus in murine
      neuroblastoma cells.
AB  - BACKGROUND: Laboratory detection of rabies in most cases is based on detection of
      the antigen by fluorescent antibody test, however, in weak positive cases
      confirmative laboratory diagnosis depends on widely accepted mouse inoculation
      test. Cell lines like neuroblastoma have been used to isolate the virus with
      greater success not only to target for diagnosis, but also for molecular studies
      that determine the epidemiology of the circulating street rabies strains and in
      studies that look at the efficiency of the developed monoclonal antibodies to
      neutralize the different rabies strains. Due to the recent issues in obtaining
      ethical permission for mouse experimentation, and also the passages required in
      the cell lines to isolate the virus, we report herewith a co-culture protocol
      using the murine neuroblastoma (MNA) cells, which enable quicker isolation of
      street rabies virus with minimum passages. OBJECTIVE: This study is not to have
      an alternative diagnostic assay, but an approach to produce sufficient amount of
      rabies virus in minimum passages by a co-culture approach in MNA cells. MATERIALS
      AND METHODS: The MNA cells are co-cultured by topping the normal cells with
      infected cells every 48 h and the infectivity was followed up by performing
      direct fluorescent-antibody test. RESULTS: The co-culture approach results in
      100% infectivity and hence the use of live mouse for experimentation could be
      avoided. CONCLUSION: Co-culture method provides an alternative for the situations
      with limited sample volume and for the quicker isolation of virus which warrants
      the wild type strains without much modification.

PMID- 27047149
TI  - Reproductive responses of dairy cows with ovarian cysts to simultaneous human
      chorionic gonadotropin or gonadotropin-releasing hormone and cloprostenol
      compared to gonadotropin-releasing hormone alone treatment.
AB  - AIM: Bovine ovarian cysts are a common cause of economic loss in modern dairy
      herds. The objective of the present study was to evaluate the reproductive
      responses to three protocols using hCG, GnRH and cloprostenol when the definite
      diagnosis of the type of ovarian cyst is/is not possible in dairy cows. MATERIALS
      AND METHODS: A total of 144 lactating dairy cows with ovarian cysts were divided
      into three groups. At diagnosis (Day 0), cows in Group 1 (the conventional
      method, n=47) were injected with 0.02 mg of a GnRH analogue i.m. (Buserelin);
      cows in Group 2 (n=47) were intramuscularly treated with 0.02 mg Buserelin plus
      500 ug cloprostenol; and cows in Group 3 (n=50) were intramuscularly treated with
      1500 IU hCG plus 500 ug cloprostenol. All cows received 500 ug cloprostenol
      intramuscularly on Day 10. RESULTS: No statistically significant differences were
      found in the recovery time, interval to conception, conception rate at first AI,
      and pregnancy rates by Days 70 and 100 after treatment among the three groups.
      CONCLUSIONS: Simultaneous treatment of ovarian cysts with hCG or GnRH and
      cloprostenol appeared to have no advantage over the conventional method, GnRH
      alone, in dairy cows. Furthermore, hCG and GnRH have an equal therapeutic effect
      in cows with ovarian cysts.

PMID- 27047150
TI  - Morphometric evaluation of seminiferous tubule and proportionate numerical
      analysis of Sertoli and spermatogenic cells indicate differences between
      crossbred and purebred bulls.
AB  - AIM: The present study compared the testicular cytology and histology between
      crossbred (Holstein-Friesian [HF] * Tharparkar) and purebred (HF and Tharparkar)
      bulls to find out differences if any. MATERIALS AND METHODS: Four peripubertal
      bulls from each breed were utilized for the study. Through percutaneous needle
      aspiration biopsy, Sertoli and spermatogenic cells were extracted, and
      morphometry was studied. For histological studies, testicular tissues obtained
      through unilateral castration were utilized. Sertoli cells specific GATA4
      antibody was used to study the population of Sertoli cells in the seminiferous
      tubule through immunofluorescence. RESULTS: The testicular weight, volume, and
      scrotal circumference differed significantly among the breeds. The diameter and
      area of the seminiferous tubule was high in HF, followed by Karan Fries (KF), and
      Tharparkar bulls. However, the degree of compactness, based on qualitative
      evaluation, was high in Tharparkar followed by KF and HF bulls. The intensity of
      Leydig cells was higher in Tharparkar bulls followed by KF and HF. The proportion
      of Sertoli cells was higher (p<0.05) in HF and Tharparkar bulls compared to KF
      bulls. CONCLUSION: It may be concluded that variations exist in testicular
      components of the breeds studied and the proportion of Sertoli cells in relation
      to spermatogenic cells was significantly lower in crossbred bulls compared to
      purebred bulls.

PMID- 27047151
TI  - Preparation and storage stability of meat spread developed from spent hens.
AB  - AIM: The present study was carried out to develop a meat spread as a healthier
      alternative to already existing meat products utilizing undervalued spent hen
      meat to add a new dimension to meat products. MATERIALS AND METHODS: Carcasses
      were processed within 30 min of slaughter and conditioned at 4+/-1 degrees C for
      about 24 h and then braised along with other ingredients to get the final
      product. The products were evaluated for proximate composition, peroxide values,
      pH, microbiological, and sensory qualities as per standard procedures. RESULTS:
      The mean percent values for moisture, crude protein, ether extract, and total ash
      content of developed product were 58.75+/-0.32, 9.12+/-0.44, 11.19+/-0.16, and
      2.35+/-0.17, respectively. No significant difference was observed for mean
      coliform and the yeast and mold counts with the progression of storage period,
      but samples differed significantly for mean pH, thiobarbituric acid and total
      viable plate count during storage of meat spread. A progressive decline in mean
      sensory scores was recorded along with the increase in storage time. CONCLUSION:
      The meat spread was found to be a good alternative to process the underutilized
      spent hens for its efficient utilization for product development.

PMID- 27047152
TI  - Pharmacodynamic interaction of fenugreek, insulin and glimepiride on sero
      biochemical parameters in diabetic Sprague-Dawley rats.
AB  - AIM: This study was undertaken to assess the pharmacodynamic interaction of
      fenugreek, insulin and glimepiride on sero-biochemical parameters in
      streptozotocin-induced diabetic rats. MATERIALS AND METHODS: A total of 56 male
      Sprague-Dawley rats, randomly divided into seven Groups. Group 1: Non-diabetic
      control; Group 2: Streptozotocin induced diabetic control; Groups 3, 4 and 5 were
      treated with insulin, glimepiride and fenugreek seed powder, respectively; Groups
      6 and 7: Insulin + fenugreek seed powder treatment and glimepiride + fenugreek
      seed powder treatment respectively, in diabetic rats. Body weights, blood
      glucose, lipids total cholesterol (TC), high-density lipoprotein (HDL), low
      density lipoprotein (LDL), triglycerides (TG) and proteins (total protein,
      albumin, globulin, A/G ratios) were studied at different time intervals. Rats
      were sacrified at the end of 8 weeks, pancreas and aorta collected for
      histopathological study. RESULTS: The results of Group 2 showed significantly
      (p<0.05) higher concentration of glucose, TC, TG, LDL, globulin, A/G ratios and
      significantly (p<0.05) lower concentration of albumin, total protein, HDL and
      body weights when compared to Group 1 at the end of 4(th) and 8(th) weeks
      intervals with marked alteration in histopathology of pancreas and aorta. All the
      treatment Groups 3-7 showed significantly (p<0.05) improvement in the all the
      parameters and the Groups 6 and 7 showed highest decrease in the concentration
      blood glucose, TC, TG, LDL and increase in the albumin, total protein and body
      weights during 6(th) and 8(th) week, respectively. CONCLUSION: The treatment with
      fenugreek, insulin and glimepiride countered the alteration in the sero
      biochemical parameters in diabetic rats, and their combination was found a
      positive interaction in improving the sero biochemical status of diabetic rats.

PMID- 27047153
TI  - Effect of Aloe vera and clove powder supplementation on carcass characteristics,
      composition and serum enzymes of Japanese quails.
AB  - AIM: The aim was to study the effect of Aloe vera and clove powder
      supplementation on carcass characteristics, composition and serum enzymes of
      Japanese quails. MATERIALS AND METHODS: The study was conducted on 120-day-old
      Japanese quails, which were randomly divided into four treatment groups viz. T1
      control, T2-0.5% A. vera, T3-0.5% clove, and T4-(0.25% A. vera + 0.25% clove)
      powder, each having three replications consisting of ten Japanese quails. The
      birds in control group (T1) were fed no supplement whereas in treatments T2-T4
      birds were supplemented with A. vera leaf powder, clove, and mixture of both
      (powdered form) at 0.5, 0.5, and 0.25+0.25% of feed, respectively. After 7 days
      of brooding, a feeding trial of 35 days was conducted. On 35(th) day of trial
      birds were sacrificed and dressing percentage, cut up parts, organ weight,
      processing losses and carcass meat composition of the breast, thigh, and
      drumstick were recorded. Blood samples were collected on the same day and serum
      was separated to evaluate serum enzymes alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST). RESULTS: It showed significantly (p<0.05)
      higher values of dressing percentage with and without giblet and breast weight in
      the T2-T4 group as compared to the T1 group. No significant (p>0.05) differences
      were observed in giblet weight, other cut up parts and composition of the breast,
      thigh, and drumstick muscles in all the treatment groups. Serum ALT and AST did
      not vary significantly among different treatment groups. CONCLUSION: A. vera and
      clove supplementation improved the dressing percentage and breast weight without
      adversely affecting the meat composition and serum enzymes. Thus, these can be
      used as a growth promoter in Japanese quails.

PMID- 27047154
TI  - Isolation and identification of Salmonella from diarrheagenic infants and young
      animals, sewage waste and fresh vegetables.
AB  - AIM: This study was carried out to determine the prevalence, distribution, and
      identification of Salmonella serotypes in diarrheagenic infants and young
      animals, including sewage waste and fresh vegetables. MATERIALS AND METHODS: A
      total of 550 samples were processed for the isolation of Salmonella spp., using
      standard microbiological and biochemical tests. Further polymerase chain reaction
      (PCR) detection of Salmonella genus was carried out using self-designed primers
      targeting invA gene and thereafter identification of important serotypes namely
      Salmonella Enterica serovar Typhimurium, Salmonella Enterica serovar Enteritidis,
      Salmonella Enterica serovar Typhi was performed using published standardized
      multiplex PCR. RESULTS: An overall low prevalence of 2.5% (14/550) was observed.
      The observed prevalence of Salmonella spp. in diarrheagenic infants was 1.2%
      (05/400), diarrheagenic young animals 4% (02/50), sewage waste 10% (05/50), and
      fresh vegetables 4% (02/50), respectively. In diarrheagenic infants, of the five
      Salmonella isolates identified, two were Salmonella Typhimurium, two Salmonella
      Enteritidis, and one was unidentified and hence designated as other Salmonella
      serovar. All the Salmonella isolates identified from diarrheagenic young animals
      and sewage waste belonged to other Salmonella serovar, whereas, of the two
      isolates recovered from fresh vegetables, one was identified as other Salmonella
      serovar, and one as Salmonella Typhimurium, respectively. CONCLUSION: Isolation
      of Salmonella spp. especially from sewage waste and fresh vegetable is a matter
      of great concern from public health point of view because these sources can
      accidentally serve as a potential vehicle for transmission of Salmonella spp. to
      animals and human beings.

PMID- 27047155
TI  - Ethnoveterinary medicinal plants: Preparation and application methods by
      traditional healers in selected districts of southern Ethiopia.
AB  - AIM: The aim was to document the ethnoveterinary medicinal plants, their
      preparation, and application methods used by traditional healers in treating
      different animal diseases, in four districts with different culture and languages
      in southern Ethiopia. MATERIALS AND METHODS: Information of ethnoveterinary
      medicinal plants was obtained through in-depth direct interview with the local
      healers and field observations. A descriptive statistics was used to analyze the
      reported ethnoveterinary medicinal plants and associated indigenous knowledge.
      The informant consensus factor (ICF) was calculated for each category of diseases
      to identify the agreements of the informants on the reported cures. Preference
      ranking was used to assess the degree of effectiveness of certain medicinal
      plants against most prevalent animal diseases in the area. RESULTS: The healers
      had a very high intention to keep their traditional knowledge secrete and none of
      them was ready to transfer their knowledge either freely or on incentive bases to
      other people; they need to convey their knowledge only to their selected scions
      after getting very old. A total of 49 plant species used to treat 26 animal
      ailments were botanically classified and distributed into 34 families. The most
      commonly used plant parts for remedy preparations were leaves (38.8%), followed
      by whole roots (20.4%). Calpurnia aurea (Ait.) Benth was the most preferred
      effective treatment against external parasite and skin problem, which is the most
      prevalent disease with the highest ICF (0.68). CONCLUSION: The study suggests
      that the community of the study districts depend largely on ethnoveterinary
      medicinal plants for the treatment of different animal ailments though the
      healers have a very high intention to keep their traditional knowledge secrete.
      Commonly reported plant species need to be tested for their antimicrobial
      activities in vitro and validated their active ingredients in order to recommend
      effective preparations and treatments to this community.

PMID- 27047156
TI  - A comparative study on the blood and milk cell counts of healthy, subclinical,
      and clinical mastitis Karan Fries cows.
AB  - AIM: The present study was aimed to study the use of cell counts as an early
      indicator of mammary health. MATERIALS AND METHODS: Milk and blood cell counts
      were estimated from 8 healthy, 8 subclinical (SCM), and 8 clinically mastitis
      (CM) groups of Karan Fries (KF) cows. RESULTS: Total leucocyte counts and
      neutrophil percent in blood and milk somatic cells and milk neutrophil percent of
      healthy cows increased significantly (p<0.05) in SCM cows and CM cows. Viability
      of blood and milk neutrophils was more in healthy cows, but decreased
      significantly (p<0.05) in SCM and CM cows. Significant (p<0.05) decrease were
      also observed in both the blood and milk lymphocytes and monocytes of SCM and CM
      cows. Phagocytic activity (PA) of blood neutrophils also decreased significantly
      (p<0.05) in SCM cows. There was no difference between the PA of SCM and CM cows.
      Milk neutrophil percent was more in the SCM and clinically infected milk than in
      the blood of these cows. About 96-97% of the neutrophils had segmented nucleus in
      both healthy and subclinical milk, whereas, 2-3% were having band shaped or
      immature nuclei. There was a significant decrease in the segmented neutrophils,
      whereas, band neutrophils increase significantly to about 5% in the infected milk
      of mastitic cows. Viability of the milk neutrophils decreased more in case of
      subclinical and clinical milk as compared to that of blood. PA was found to be
      highest in the milk of healthy group of cows, but decreased significantly
      (p<0.05) in subclinically infected cows. However, there was no difference between
      the PA of milk neutrophils of SCM and CM cows. PA of milk was also found to be
      significantly lower in the milk of healthy cows when compared to that of blood
      neutrophils. CONCLUSION: This study indicated that percent neutrophils and their
      type in conjunction with milk somatic cell counts can be used as a more reliable
      indicator of mammary health in cows.

PMID- 27047157
TI  - Study of short lactation in Sahiwal cattle at organized farm.
AB  - AIM: The aim was to study the associated factors and extent of short lactations
      in Sahiwal cattle maintained under organized herd. MATERIALS AND METHODS: The
      present study was conducted on Sahiwal cattle (n=530), utilizing 1724 lactation
      records with respect to lactation length (LL), spread over a period of 15 years
      (1997-2011), maintained at Livestock Research Center, National Dairy Research
      Institute, Karnal. Observations of LL were analyzed by descriptive statistical
      analysis in order to know the extent of short lactation of animals in the herd.
      Paternal Half sib method was used to estimate the genetic parameters, i.e.,
      heritability, genetic, and phenotypic correlation. The influence of various non
      genetic factors (season of calving, the period of calving, parity, type of
      calving, and season of drying) on LL was studied by least squares analysis of
      variance technique. RESULTS: The least squares means for LL was found to be
      215.83+/-3.08 days. Only 32.48% of total lactation records were fell in the range
      of 251-350 days of LL, while more than three-fourth (76%) of total observations
      were failed to reach the standard level of 305 milking days. LL class ranges from
      251 to 300 days accommodated maximum number of observations (19.2%). The
      heritability estimate of LL was 0.22+/-0.07. Positive correlations were found
      between LL and service period, LL and 305 or less days milk yield, LL and calving
      interval; whereas dry period was negatively correlated with the LL. The least
      squares analysis had shown that LL was significantly (p<0.01) influenced by the
      period of calving, type of calving, and season of drying. Significantly higher LL
      (276.50+/-7.21 days) was found in animals calved in the first period than those
      calved in other periods. The cows dried during summer season had the shortest LL
      (188.48+/-7.68 days) as compared to other seasons. CONCLUSION: Present findings
      regarding short lactations occurrence may be alarming for the indigenous herd,
      demanding comprehensive study with the larger data set. Since LL was influenced
      by various environmental factors suggesting better managerial tools, besides
      special attention on the milch animals going to dry during the summer season.

PMID- 27047158
TI  - Hematocrit alterations and its effects in naturally infected indigenous cattle
      breeds due to Trypanosoma spp. on the Adamawa Plateau - Cameroon.
AB  - AIM: An experimental study was carried out on 148 naturally infected indigenous
      cattle breeds with either single or mix infections of various species of
      trypanosomes. The objectives of this study were to determine the species of
      trypanosomes, observe their hematopathological consequences on host-related risk
      factors and to determine the packed cell volume (PCV) of the infected group.
      MATERIALS AND METHODS: The buffy coat method (BCM) which is a variant of the
      hematocrit centrifugation method was used for the parasitological and
      hematological analysis. The May Grunwald-Giemsa method was also used for the
      identification of different trypanosome species. RESULTS: The infection rate in
      accordance with the various trypanosomes was as follows: Trypanosoma congolense +
      Trypanosoma brucei (1.35%), Trypanosoma vivax + T. brucei (1.35%), T. congolense
      + T. vivax (8.11%), T. congolense + T. vivax + T. brucei (8.78%), T. brucei
      brucei (11.48%), T. vivax (20.94%), T. congolense (47.97%). The infection rate
      with respect to breeds showed the following results - Brahman (1.0%), Red Fulani
      (5.2%), White Fulani (6.5%) and Gudali (16.7%), with no statistical significant
      difference (p>0.05). The combined mean PCV of single as well as mix infections
      was not statistically significant (p>0.05). The mean PCV of males (25.64+/-5.08
      standard deviation [SD]) which was lower than that of females (30.82+/-4.94 SD)
      was statistically significant (p<0.05). The body condition of infected animals
      with sex showed that a greater proportion of males with "Poor" and "Medium"
      conditions showed high prevalence than females with the same conditions, with a
      significant difference (p<0.05). However, females showed a "Good" condition than
      males even though it was not statistically significant (p>0.05). The PCV profile
      of the infected group showed that the highest proportion of infected animals had
      PCV of <=31% than PCV >31%. The mean weight of the animals was (265.41+/-95.36
      SD). A scatter-linear plot of infected buffy coat against mean PCV showed a
      negative parametric correlation. CONCLUSION: Distinguished Trypanosoma spp.
      pathogenicity, emaciation and weight loss related anemia, poor body condition,
      sex and the response of different breeds to various trypanosomes were highly
      affected and are of vital importance in diagnosis and act as a contribution to
      future control and treatment plans in this area.

PMID- 27047159
TI  - Diagnosis of urinary bladder diseases in dogs by using two-dimensional and three
      dimensional ultrasonography.
AB  - AIM: The objective of this study was to obtain and compare two-dimensional (2D)
      and three-dimensional (3D) ultrasonographic images of the urinary bladder in
      different disease conditions. MATERIALS AND METHODS: The present study was
      conducting on total 10clinical cases of the urinary bladder in dogs. The
      ultrasound (US) machine used for this study was 3D US machine (Nemio-XG: Toshiba,
      Japan) having a four-dimensional volumetric probe. RESULTS: In the present study,
      the inflamed thickened wall was clearly visible with the distinction of different
      layers of the urinary bladder wall in some of the cases of cystitis using 2D
      ultrasonography. In 3D sonogram, the urinary bladder was visualized as a large
      anechoic structure with no distinction of different layers of the bladder wall.
      The cystoliths were clearly visible as hyperechoic structures with distal
      acoustic shadow in 2D sonogram and appeared as a bright echogenic area in 3D
      sonogram. In case of urinary bladder neoplasia in 2D ultrasonogram, the bladder
      lumen was found to be occluded with a large growth imaged as focal anechoic areas
      in the tissue of mixed echogenicity with small hyperechoic dots in this tissue
      parenchyma. In 3D ultrasonogram, a tissue of mixed echogenicity of pus was also
      observed. CONCLUSION: From the present study it was concluded that 2D and 3D
      ultrasonography is very helpful for diagnosis of different clinical conditions of
      the urinary bladder such as cystitis, cystoliths, and urinary bladder neoplasia.
      The cavity of urinary bladder was more clearly visualized in 3D ultrasonography,
      but the distinction of different layers of the bladder wall was visualized only
      in 2D ultrasonography. The distinct shadow of pus and cystoliths were visible in
      2D ultrasonogram. The visualization of pus in 3D ultrasonography was done for the
      first time in present study.

PMID- 27047160
TI  - Modeling of spatial distribution for scorpions of medical importance in the Sao
      Paulo State, Brazil.
AB  - AIM: In this work, we aimed to develop maps of modeling geographic distribution
      correlating to environmental suitability for the two species of scorpions of
      medical importance at Sao Paulo State and to develop spatial configuration
      parameters for epidemiological surveillance of these species of venomous animals.
      MATERIALS AND METHODS: In this study, 54 georeferenced points for Tityus
      serrulatus and 86 points for Tityus bahiensis and eight environmental indicators,
      were used to generate species distribution models in Maxent (maximum entropy
      modeling of species geographic distributions) version 3.3.3k using 70% of data
      for training (n=38 to T. serrulatus and n=60 to T. bahiensis) and 30% to test the
      models (n=16 for T. serrulatus and n=26 for T. bahiensis). The logistic threshold
      used to cut models in converting the continuous probability model into a binary
      model was the "maximum test sensitivity plus specificity," provided by Maxent,
      with results of 0.4143 to T. serrulatus and of 0.3401 to T. bahiensis. The models
      were evaluated by the area under the curve (AUC), using the omission error and
      the binomial probability. With the data generated by Maxent, distribution maps
      were produced using the "ESRI((r)) ArcGIS 10.2.2 for Desktop" software. RESULTS:
      The models had high predictive success (AUC=0.7698+/-0.0533, omission
      error=0.2467 and p<0.001 for T. serrulatus and AUC=0.8205+/-0.0390, omission
      error=0.1917 and p<0.001 for T. bahiensis) and the resultant maps showed a high
      environmental suitability in the north, central, and southeast of the state,
      confirming the increasing spread of these species. The environmental variables
      that mostly contributed to the scorpions species distribution model were rain
      precipitation (28.9%) and tree cover (28.2%) for the T. serrulatus and
      temperature (45.8%) and thermal amplitude (12.6%) for the T. bahiensis.
      CONCLUSION: The distribution model of these species of medical importance
      scorpions in Sao Paulo State revealed a higher environmental suitability of these
      species in the regions north, central, and southeast of the state, warning to
      emergencies actions for prevention and surveillance from scorpion stings in
      several counties. There is also a need to best conservation strategies related to
      neighboring territories, with the implementation of new environmental protected
      areas and measures of spread control of these species in urban areas of several
      counties.

PMID- 27047161
TI  - Effect of thawing methods on frozen semen quality of yak (Poephagus grunniens L.)
      bulls.
AB  - AIM: To evaluate different thawing temperatures and duration on the post-thaw
      semen quality of Indian yaks bulls. MATERIALS AND METHODS: Semen ejaculates from
      four different yak bulls were collected using artificial vagina method and
      extended with tris extender containing 6.4% glycerol at 35 degrees C, cooled
      gradually from 35 degrees C to 5 degrees C at 1 degrees C/3 min and equilibrated
      at 4-5 degrees C for 4 h and frozen in French mini straws using a programmable
      bio-freezer and finally stored in liquid nitrogen. Thawing of frozen semen straws
      was carried out using three methods i.e., 35 degrees C for 60 s (thawing method
      I), 37 degrees C for 30 s (thawing method II) and 75 degrees C for 9 s (thawing
      method III). The post-thaw semen quality parameters assessed were sperm motility,
      percent live sperm, hypo-osmotic swelling test (HOST)-reacted sperm, acrosomal
      changes, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      activities in the extracellular media. RESULTS: The percent sperm motility, total
      incidence of acrosomal changes, and extracellular release of AST varied
      significantly (p<0.01) between thawing methods but live sperm and HOST-reacted
      sperm did not vary significantly between thawing methods. The percent sperm
      motility of frozen yak semen for thawing method III was significantly (p<0.05)
      higher than that for thawing methods I and II, the difference between thawing
      methods I and II being non-significant. The critical difference test revealed
      that the total incidence of acrosomal changes and extracellular release of AST
      were significantly (p<0.05) lower when thawing was done using methods I and II
      than in method III. CONCLUSION: On the basis of the present experiment, we can
      conclude that barring the post-thaw sperm motility, thawing of frozen yak semen
      in water either at 35 degrees C for 60 s or 37 degrees C for 30 s gives better
      post-thaw semen quality than at 75 degrees C for 09 s.

PMID- 27047162
TI  - Two-dimensional and three-dimensional ultrasonography for pregnancy diagnosis and
      antenatal fetal development in Beetal goats.
AB  - AIM: The objective of this study was to compare two-dimensional (2D) and three
      dimensional (3D) study of the pregnant uterus and antenatal development of the
      fetus. MATERIALS AND METHODS: 2D and 3D ultrasound were performed from day 20 to
      120 of gestation, twice in week from day 20 to 60 and once in week from day 60 to
      120 of gestation on six goats. The ultrasonographic images were obtained using
      Toshiba, Nemio-XG (Japan) 3D ultrasound machine. RESULTS: On the 20(th) day of
      gestation, earliest diagnosis of pregnancy was done. First 3D ultrasonographic
      image of the conceptus, through transabdominal approach, was obtained on day 24.
      On 39(th) day, clear pictures of conceptus, amniotic membrane, and umbilicus were
      seen. On 76(th) day of gestation, internal organs of fetus viz heart, kidney,
      liver, urinary bladder, and stomach were seen both in 2D and 3D images. 3D
      imaging showed better details of uterine structures and internal organs of the
      fetus. CONCLUSIONS: Comparing 3D images with 2D images, it is concluded that 2D
      was better in visualizing fluid while 3D images were better to view details of
      attachment of fetus with endometrium.

PMID- 27047163
TI  - Animal health care seeking behavior of pets or livestock owners and knowledge and
      awareness on zoonoses in a university community.
AB  - AIM: We investigated the attitude of pets or livestock owning households in a
      university community to animal health care services and assessed the knowledge
      and awareness level of the residents on zoonoses. MATERIALS AND METHODS:
      Structured questionnaire was used to obtain information on demography, pet or
      livestock ownership, animal health care seeking behavior, awareness and knowledge
      of zoonoses from 246 households. We did descriptive statistics and bivariate
      analysis to determine the level of association in discrete variables between
      owners and non-owners of pets or livestock at a significant level of p<0.05.
      RESULTS: Of the 246 respondents, 80 (32.5%) were either pet or livestock owners.
      The animal health care seeking behavior of the 80 pets or livestock owners in
      terms of treatment and vaccination was 70%. Of the 56 (70%) who provided health
      care services for their animals, about 48 (85.7%) engaged the services of a
      veterinarian. Dog owning households (42) had the highest frequency of treating
      their pets against endoparasites (97.6%); ectoparasites (81%) and vaccination
      against diseases (73.8%). Of the 246 respondents, only 47 (19.1%) have heard of
      the term zoonoses. Of the considered zoonoses; their awareness of rabies (79.3%)
      was the highest, followed by Lassa fever (66.3%), the least was pasteurellosis
      with 18.7%. Having pets or livestock was significantly associated (p=0.04) with
      rabies awareness. However, there is no significant difference in the level of
      awareness of zoonoses; knowledge of zoonoses, knowledge of prevention of zoonoses
      and knowledge of risk of zoonoses between owners and non-owners of pets or
      livestock. CONCLUSION: The animal health care seeking behavior of households with
      pets or livestock is good and should be encouraged. Public education should be
      created for other zoonoses aside from rabies, Lassa fever, and avian influenza.

PMID- 27047164
TI  - Microsatellite DNA typing for assessment of genetic variability in Marwari breed
      of Indian goat.
AB  - AIM: To estimate existing within-breed genetic variability in Marwari goats under
      field conditions and the generated data that can be used to determine genetic
      relationships with other breed of goats. MATERIALS AND METHODS: A total of 146
      blood samples of goats of Marwari breed were randomly collected from genetically
      unrelated animals from different villages of Bikaner Districts of Rajasthan,
      India. Genomic DNA was extracted from whole blood using proteinase K-digestion
      followed by standard phenol-chloroform extraction procedure at room temperature
      and confirmed through horizontal electrophoresis on 0.8% agarose gel containing
      ethidium bromide. Fifteen caprine microsatellite markers were used to estimate
      genetic variability among the goats of Marwari breed in terms of allelic and
      genotype frequencies, heterozygosities and polymorphism information content (PIC)
      value. RESULTS: A total of 74 alleles were contributed by Marwari goat across all
      15 microsatellite loci. The number of alleles per locus varied from two (ILSTS
      087) to 9 (ILSTS-058) alleles, with a mean of 4.93 whereas the effective number
      of allele varied from 1.35 (ILSTS-005) to 3.129 (ILSTS011) with a mean of 2.36.
      The effective number of allele is lesser than observed number at all the loci.
      Allelic sizes ranged from 125 bp (ILSTS-028 and ILSTS-033) to 650 bp (ILSTS-011
      and ILSTS-019). The expected heterozygosity ranged from 0.240 (locus ILSTS-005)
      to 0.681 (locus ILSTS-011), with an average value of 0.544. The observed
      heterozygosity (Ho) ranged from 0.1428 (locus ILSTS-087) to 0.9285 (locus ILSTS
      034), with an average value of 0.5485 indicates substantial and very good number
      of heterozygotes, in the population. The highest PIC value (1.1886) was observed
      at ILSTS-044 locus and least (0.0768) at ILSTS-065 locus for Marwari goat.
      CONCLUSION: Microsatellite analysis revealed a high level of polymorphism across
      studied microsatellite markers and informativeness of the markers for genetic
      diversity analysis studies in Marwari goats. This high level of polymorphism can
      be utilized to plan future biodiversity studies to exploit the uniqueness and
      adaptability of this breed to Western Rajasthan. Most studied microsatellite
      markers proving to be good candidates for genetic characterization and diversity
      analysis of this breed of goat.

PMID- 27047165
TI  - Assessment of variable drinking water sources used in Egypt on broiler health and
      welfare.
AB  - AIM: This study assessed the impact of four water sources used as drinking water
      in Egypt for broiler chickens on its performance, carcass characteristic,
      hematological, and immunological responses. MATERIALS AND METHODS: A total of 204
      unsexed 1-day old Indian River broiler chickens were used in this study. They
      were randomly allocated into four treatment groups of 51 birds in each, with
      three replicates, 17 birds per replicate. Groups were classified according to
      water source they had been received into (T1) received farm tap water; (T2)
      received filtered tap water (T3) received farm stored water at rooftop tanks,
      (T4) received underground (well) water. RESULTS: All water sources showed no
      significant differences among treated groups at (p>0.05) for most of the
      performance parameters and carcass characteristics. However (T2) group showed
      higher records for body weight (BWT), BWT gain (BWG), feed conversion ratio,
      bursa weight, serum total protein, globulin (G), albumin (A) and A/G ratio, Ab
      titer against New castle disease virus vaccine. On the other hand, it showed
      lower records for water intake (WI), WI/Feed intake ratio, total leukocytes count
      %, heterophil %, lymphocyte %, H/L ratio, liver weight, glutamic oxaloacetic
      transaminase, glutamic pyruvic transaminase, serum uric acid and creatinine.
      Where filtered water reverse osmosis showed lowest records for bacterial load,
      the absence of coliform bacteria, total dissolved solids (TDS), electrical
      conductivity (EC) and salinity. On the other hand stored water showed higher
      numerical values for TDS, EC, alkalinity, salinity, pH, bacterial count, and
      coliform count. CONCLUSION: Base on the results of this study, it is concluded
      that different water sources could safely be used as drinking water for poultry;
      as long as it is present within the acceptable range of drinking water quality
      for chickens. Suggesting the benefits of treatment of water sources on improving
      chickens' health and welfare. Draw attention to the importance of maintaining the
      hygienic quality of stored water.

PMID- 27047166
TI  - Seroprevalence of foot and mouth disease virus infection in pigs from Zuru,
      Nigeria.
AB  - AIM: This study was conducted to determine the seroprevalence and distribution of
      foot and mouth disease virus (FMDV) infection in pigs from Zuru, Kebbi State,
      Nigeria. MATERIALS AND METHODS: Cross-sectional serological surveys were
      conducted between May and December 2013 using the immunochromatography assay
      technique. Structured questionnaires were administered to households identified
      at pig rearing areas to obtain the population structures and some information on
      managemental practices. RESULTS: A total number of 849 pigs were enumerated at 37
      pigs rearing households. Tudun wada had the largest concentration of pigs (237
      pigs), while Dabai has the least (38 pigs). A total of 250 blood samples were
      collected, of which 45 (18%) were positive; Zango has the highest seroprevalence
      (1.6%), while Dabai recorded the least (0.4%). Based on sex and age, the
      infection was higher in female (10.4%) and young pigs (11.6%) than male (7.6%)
      and adult pigs (6.4%), respectively. There was no significant (p>0.05)
      association between infection and pig rearing areas, sex, and age. Furthermore,
      none of the 250 pigs examined for classical FMDV lesions was positive.
      CONCLUSION: The results of this study showed that FMD is an important disease of
      pigs in the study areas. This result justifies the need for more attention and
      subsequent molecular study to identify the circulating FMDV in the area, which
      will help in the implementation of effective control measures.

PMID- 27047167
TI  - Study on prevalence of Fasciolosis in buffaloes at Anand and Ahmedabad districts,
      Gujarat, India.
AB  - AIM: This study was undertaken to derive the prevalence rate of Fasciolosis in
      buffaloes by a collection of fecal and liver samples from Anand and Ahmedabad
      districts' local slaughter houses. MATERIALS AND METHODS: Fecal and liver samples
      were collected during ante- and post-mortem examination, respectively, and
      brought to the department laboratory preserved in 10% formalin for further
      processing. Fecal samples were processed with qualitative examination viz.;
      sedimentation technique for identification of the ova. Liver samples were also
      examined for the presence of gross parasites. RESULTS: The highest prevalence
      rate was observed in the month of December (25.97% fecal and 33.33% liver
      samples) and lowest in the month of May (10.71% fecal and 11.76% liver samples)
      at Anand district. In the area of Ahmedabad district, the highest prevalence rate
      was recorded in the month of October and February (26.98%) and lowest in the
      month of May (10.34%) for the fecal and highest prevalence was observed in the
      month of February (26.98%) and lowest in May (11.11%) for the liver samples.
      CONCLUSION: It can be concluded that the heavy infection is present in Anand and
      Ahmedabad districts, especially in the month of winter followed by monsoon and
      the least in summer.

PMID- 27047168
TI  - Molecular identification and genetic diversity of open reading frame 7 field
      isolated porcine reproductive and respiratory syndrome in North Sumatera,
      Indonesia, in the period of 2008-2014.
AB  - AIM: Molecular identification and genetic diversity of open reading frame 7
      (ORF7) of field isolated porcine reproductive and respiratory syndrome virus
      (PRRSV) in North Sumatera, Indonesia, in the period of 2008-2014. MATERIALS AND
      METHODS: A total of 47 PRRSV samples were collected from the death case of pigs.
      The samples were collected from different districts in the period of 2008-2014
      from North Sumatera province. Two pairs of primer were designed to amplify ORF7
      of Type 1 and 2 PRRSV based on the sequence of reference viruses VR2332 and
      Lelystad. Viral RNAs were extracted from samples using PureLinkTM micro-to-Midi
      total RNA purification system (Invitrogen). To amplify the ORF7 of PRRSV, the
      synthesis cDNA and DNA amplification were performed by reverse transcription
      polymerase chain reaction (RT-PCR) and nested PCR method. Then the DNA sequencing
      of PCR products and phylogenetic analysis were accomplished by molecular
      evolutionary genetics analysis version 6.0 software program. RESULTS: RT-: PCR
      and nested PCR used in this study had successfully detected of 18 samples
      positive PRRS virus with the amplification products at 703bp and 508bp,
      respectively. Sequencing of the ORF7 shows that 18 PRRS viruses isolated from
      North Sumatera belonged to North American (NA). JXA1 Like and classic NA type
      viruses. Several mutations were detected, particularly in the area of nuclear
      localization signal (NLS1) and in NLS2. In the local viruses, which were related
      closed to JXA1 virus; there are two differences in amino acids in position 12 and
      43 of ORF7. Our tested viruses showed that the amino acid positions 12 and 43 are
      Asparagine and Arginine, while the reference virus (VR2332, Lelystad, and JXA1)
      occupied both by Lysine. Based on differences in two amino acids at position 12
      and 43 showed that viruses from North Sumatera has its own uniqueness and related
      closed to highly pathogenic PRRS (HP-PRRS) virus (JXA1). CONCLUSION: The results
      demonstrated that North Sumatera type PRRS virus has caused PRRS outbreaks in pig
      in North Sumatera between 2008 and 2014. The JAX1 like viruses had unique amino
      acid residue in position 12 and 43 of asparagine and lysine, and these were
      genetic determinants of North Sumatera viruses compared to other PRRS viruses.

PMID- 27047169
TI  - Effect of deep litter housing and fermented feed on carcass characteristics and
      meat quality of crossbred Hampshire pigs.
AB  - AIM: The objective of the study was to evaluate the effect of deep litter housing
      and fermented feed on carcass characteristics and meat quality of crossbred
      Hampshire pigs. MATERIALS AND METHODS: Forty-eight weaned crossbred Hampshire
      piglets of 2 months age (24 males and 24 females) were selected for the
      experiment. The piglets were randomly assigned into 4 homogenous experimental
      groups with 6 males and 6 females each: E1; reared on a conventional housing and
      fed with a fermented diet, E2; reared on a deep litter housing system and fed
      with a fermented diet, E3; reared on a deep litter housing system and fed with a
      conventional diet and C; reared on a conventional housing system and fed with a
      conventional diet. The study was continued up to 32 weeks of age and at the end
      of this period, 6 animals (3 males and 3 females) from each experimental group
      were slaughtered to evaluate carcass traits and meat quality characteristics.
      RESULTS: Pre-slaughter weight, hot carcass weight, and dressing percentage were
      significantly (p<0.01) affected by feeding fermented diet and deep litter housing
      while carcass traits, i.e., carcass length, backfat thickness, and loin eye area
      were not affected. The edible offal; liver and heart weight (p<0.05) differed
      significantly while kidney weight showed no difference. The inedible offal; head
      weight (p<0.01) and lung weight revealed a significant difference (p<0.05) while
      spleen and stomach weight showed no difference among the experimental groups. The
      wholesale cuts and meat: bone ratio of pigs also differed significantly among the
      groups. Morphometry of small and large intestine also showed a significant
      difference. Chemical composition of pork viz., moisture and total ash content was
      influenced by the treatment, while crude protein and ether extract content were
      not affected. Mineral composition of pork also showed no significant difference.
      Color characteristics of Longissimus dorsi muscle showed a significant difference
      in L* and a* value while parameter b* was not affected. The tenderness of meat
      showed significant difference among the groups (p<0.01). CONCLUSION: Crossbred
      Hampshire pigs being reared on fermented feed and deep litter housing could
      produce highlygraded carcass and improvement in meat quality.

PMID- 27047170
TI  - Preparation and effects of nano mineral particle feeding in livestock: A review.
AB  - Nano minerals are widely used in diversified sectors including agriculture,
      animal, and food systems. Hence, their multiple uses provoke the production of
      nanomaterials at the laboratory level, which can be achieved through physical,
      chemical or biological methods. Every method is having its own merits and
      demerits. But keeping all in mind, chemical methods are more beneficial, as
      uniform nano-sized particles can be produced, but the use of corrosive chemicals
      is the main demerits. When it comes to environmental issues, biological methods
      are better as these are free from corrosive chemicals, but maintaining the
      culture media is the disadvantage. For animal feeding, chemical methods are
      mostly followed to produce nano minerals as it is cheap and less time consuming.
      These nano minerals also showed their significant effects even at lower doses of
      recommendations than the conventional mineral sources. These nano minerals have
      significant growth promoting, immuno-modulatory, antibacterial effects than the
      conventional counterparts. They also alter the rumen fermentation pattern on
      supplementation in the animal feeds. Apart from these, nano minerals are reported
      to enhance the reproduction in the livestock and poultry. 

PMID- 27047171
TI  - Association of ATP1A1 gene polymorphism with thermotolerance in Tharparkar and
      Vrindavani cattle.
AB  - AIM: One of the major biochemical aspects of thermoregulation is equilibrium of
      ion gradient across biological membranes. Na(+)/K(+)-ATPase, a member of P type
      ATPase family, is a major contributor to the mechanism that actively controls
      cross-membrane ion gradient. Thus, we examined ATP1A1 gene that encodes alpha-1
      chain of Na(+)/K(+)-ATPase, for genetic polymorphisms. MATERIALS AND METHODS: A
      total of 100 Vrindavani (composite cross strain of Hariana x Holstein
      Friesian/Brown Swiss/Jersey) and 64 Tharparkar (indigenous) cattle were screened
      for genetic polymorphism in ATP1A1 gene, using polymerase chain reaction single
      strand conformation polymorphism and DNA sequencing. For association studies,
      rectal temperature (RT) and respiration rate (RR) of all animals were recorded
      twice daily for 3 seasons. RESULTS: A SNP (C2789A) was identified in exon 17 of
      ATP1A1 gene. Three genotypes namely CC, CA, and AA were observed in both,
      Vrindavani and Tharparkar cattle. The gene frequencies in Tharparkar and
      Vrindavani for allele A were 0.51 and 0.48, and for allele C were 0.49 and 0.52,
      respectively, which remained at intermediate range. Association study of
      genotypes with RT and RR in both cattle population revealed that the animals with
      genotype CC exhibited significantly lower RT and higher heat tolerance
      coefficient than CA and AA genotypes. CONCLUSION: Differential thermoregulation
      between different genotypes of ATP1A1 gene indicate that the ATP1A1 gene could be
      potentially contributing to thermotolerance in both, Tharparkar, an indigenous
      breed and Vrindavani, a composite crossbred cattle.

PMID- 27047172
TI  - Relationship of udder and teat conformation with intra-mammary infection in
      crossbred cows under hot-humid climate.
AB  - AIM: The present study was aimed to investigate the relationship of udder shape,
      teat-end shape, teat length, and teat diameter with intra-mammary infection in
      Jersey crossbred cows under hot-humid climate. MATERIALS AND METHODS: A total of
      24 lactating Jersey crossbred cows were evaluated for udder shape
      (pendulous/regular) and teat-end shape (flat/inverted/pointed) by visual
      examination, while teat length and teat diameter were measured using vernier
      caliper. Monthly milk sampling was done for 4 months of duration. Few quarters
      were found as blind or non-functional and so, a total of 366 quarter wise milk
      samples were collected at the monthly interval and subjected to somatic cell
      count (SCC) microscopically. The data on SCC were transformed into log scale and
      analyzed. RESULTS: There was a significant (p<0.01) effect of udder shape and
      teat-end shape on SCC level. The mean SCC level for pendulous udder was
      significantly (p<0.05) higher as compared to the regular shaped udder. Similarly,
      significantly (p<0.05) a higher level of mean SCC was found in flat teat-end
      shape. A significant (p<0.01) correlation was found between SCC and teat length
      as well as teat diameter. CONCLUSION: In conclusion, pendulous udder, flat and
      inverted teat-end, very long and thick teat were more susceptible to intra
      mammary infection in Jersey crossbred cows and these traits must be considered
      accordingly while selecting dairy animals for future milk production.

PMID- 27047173
TI  - Detection and sequence analysis of accessory gene regulator genes of
      Staphylococcus pseudintermedius isolates.
AB  - BACKGROUND: Staphylococcus pseudintermedius (SP) is the major pathogenic species
      of dogs involved in a wide variety of skin and soft tissue infections. The
      accessory gene regulator (agr) locus of Staphylococcus aureus has been
      extensively studied, and it influences the expression of many virulence genes. It
      encodes a two-component signal transduction system that leads to down-regulation
      of surface proteins and up-regulation of secreted proteins during in vitro growth
      of S. aureus. The objective of this study was to detect and sequence analyzing
      the AgrA, B, and D of SP isolated from canine skin infections. MATERIALS AND
      METHODS: In this study, we have isolated and identified SP from canine pyoderma
      and otitis cases by polymerase chain reaction (PCR) and confirmed by PCR
      restriction fragment length polymorphism. Primers for SP agrA and agrBD genes
      were designed using online primer designing software and BLAST searched for its
      specificity. Amplification of the agr genes was carried out for 53 isolates of SP
      by PCR and sequencing of agrA, B, and D were carried out for five isolates and
      analyzed using DNAstar and Mega5.2 software. RESULTS: A total of 53 (59%) SP
      isolates were obtained from 90 samples. 15 isolates (28%) were confirmed to be
      methicillin-resistant SP (MRSP) with the detection of the mecA gene. Accessory
      gene regulator A, B, and D genes were detected in all the SP isolates. Complete
      nucleotide sequences of the above three genes for five isolates were submitted to
      GenBank, and their accession numbers are from KJ133557 to KJ133571. AgrA amino
      acid sequence analysis showed that it is mainly made of alpha-helices and is
      hydrophilic in nature. AgrB is a transmembrane protein, and AgrD encodes the
      precursor of the autoinducing peptide (AIP). Sequencing of the agrD gene revealed
      that the 5 canine SP strains tested could be divided into three Agr specificity
      groups (RIPTSTGFF, KIPTSTGFF, and RIPISTGFF) based on the putative AIP produced
      by each strain. The AIP of SP contains serine and produce lactone ring structured
      AIP. CONCLUSION: Presence of AgrA, B, and D in all SP isolates implies the
      importance of this regulatory system in the virulence genes expression of the SP
      bacteria. SP isolates can be typed based on the AgrD auto-inducible protein
      sequences as it is being carried out for typing of S. aureus isolates. However,
      further studies are required to elucidate the mechanism of controlling of
      virulence genes by agr gene locus in the pathogenesis of soft tissue infection by
      SP.

PMID- 27047174
TI  - Prevalence, molecular characterization of Staphylococcus aureus isolated from
      cheese and in vitro antibacterial activity of silver nanoparticles against such
      strains.
AB  - AIM: The aim was to investigate cheese samples for the prevalence of
      Staphylococcus aureus, evaluate multiplex polymerase chain reaction (PCR) methods
      for S. aureus identification, as well as to determine the antibacterial activity
      of silver nanoparticles against such strains. MATERIALS AND METHODS: Total of 100
      random locally manufactured cheese samples were collected from Qena dairy
      markets, Egypt, and examined conventionally for the prevalence of S. aureus then,
      confirmation of these isolates were done using multiplex PCR. The antibacterial
      activity of silver nanoparticles against such isolates was also checked. RESULTS:
      Lower prevalence of S. aureus in Damietta cheese (54%) than in Kareish cheese
      (62%) was recorded. As well lower frequency distribution for both S. aureus (36%)
      and CNS (8%) was also reported for Damietta cheese. Using of multiplex PCR method
      for S. aureus identification have been confirmed all 58 S. aureus stains that
      were identified conventionally by detection of two PCR products on agarose gel:
      The 791 bp and the 638 bp. The correlation coefficient between conventional and
      multiplex PCR method was 0.91 and was significant at p<=0.001. Regarding
      antibacterial activity of silver nanoparticles using disk diffusion method on
      Baird Parker agar it was found that inhibition zone of silver nanoparticles
      against S. aureus, was 19.2+/-0.91 mm and it was higher than that produced by
      gentamicin (400 units/ml) 15.2+/-0.89 mm. CONCLUSIONS: The present study
      illustrated the higher prevalence of S. aureus in cheese samples that may
      constitute a public health hazard to consumers. According to the results, it can
      be concluded that silver nanoparticles can be used as an effective antibacterial
      against S. aureus. Thereby, there is a need for an appropriate study for using
      silver nanoparticles in cleaning and disinfection of equipment and in food
      packaging.

PMID- 27047175
TI  - Detection of Helicobacter pylori glmM gene in bovine milk using Nested polymerase
      chain reaction.
AB  - AIM: The aim was to detect the glmM gene of Helicobacter pylori (H. pylori) in
      cow's milk from different dairy farms in Khartoum State using Nested polymerase
      chain reaction (PCR). MATERIALS AND METHODS: A total of 50 milk samples were
      collected from different dairy farms in Khartoum State (13 from Khartoum, 24
      Khartoum North, and 13 from Omdurman Provinces). RESULTS: The generated results
      showed that 11/50 (22%) were harboring the investigated H. pylori glmM gene in
      Khartoum State (1/13 [7.7%] Khartoum, 9/24 [37.5%] Khartoum North, and 1/13
      [7.7%] Omdurman provinces, respectively). CONCLUSION: To the best of our
      knowledge, this was the first report on the detection of H. pylori glmM gene in
      cattle milk in Khartoum State. Nonetheless, the high percentages of H. pylori DNA
      detection in milk opened new avenues toward exploring the risk of human infection
      with H. pylori through the consumption of raw milk.

PMID- 27047176
TI  - Effect of feeding chayote (Sechium edule) meal on growth performance and nutrient
      utilization in indigenous pig (Zovawk) of Mizoram.
AB  - AIM: This study was planned to investigate the effect of feeding different levels
      of chayote (Sechium edule) meal by replacing standard concentrate mixture (CM) on
      the growth parameters such as feed intake, body weight gain, average daily gain
      (ADG) and feed conversion ratio (FCR), and nutrient utilization in indigenous pig
      of Mizoram. MATERIALS AND METHODS: Twenty-four growing indigenous pigs (Zovawk)
      were used to study the effect of feeding chayote (Sechium edule) meal (fruits and
      leaves at the ratio 4:1) on growth performance and nutrient utilization. They
      were allocated randomly into 4 treatment groups (G1, G2, G3, and G4). Chayote
      meal was used to replace standard CM (pig grower ration) at 0% (G1), 20% (G2),
      30% (G3), and 40% (G4). RESULTS: During the feeding trial of 90 days, it was
      found that the dry matter (DM) intake decreased as the level of chayote meal
      increased. For G1, G2, G3, and G4, the ADG (kg) was 0.24+/-0.04, 0.23+/-0.03,
      0.18+/-0.02, and 0.18+/-0.02, respectively, and the feed conversion efficiency
      was 5.42+/-0.44, 4.93+/-0.17, 5.38+/-0.05, and 5.74+/-0.53, respectively.
      However, there was no significant difference (p>0.05) among the different
      treatment groups in respect to ADG and FCR. At the end of the feeding trial,
      digestibility trial was conducted to study the effect of feeding chayote meal in
      the digestibility of the different nutrients by the experimental animals. From
      the digestibility trial, it was revealed that the digestibility coefficient of
      DM, crude protein, and crude fiber were also similar (p>0.05), although the ether
      extract digestibility in G1 was significantly low (p<0.01) as compared to G2, G3,
      and G4. CONCLUSION: Chayote meal could safely replace the standard grower ration
      up to 40% in the diet of growing local pigs without causing any adverse effects
      on growth and nutrient utilization.

PMID- 27047177
TI  - Isolation and detection of Corynebacterium pseudotuberculosis in the reproductive
      organs and associated lymph nodes of non-pregnant does experimentally inoculated
      through intradermal route in chronic form.
AB  - AIM: Corynebacterium pseudotuberculosis is the etiological agent of caseous
      lymphadenitis that affects sheep and goats. This study was designed to determine
      the presence of the causative organism in the female reproductive organs and
      associated lymph nodes in non-pregnant does experimentally inoculated through
      intradermal route in the chronic form. MATERIALS AND METHODS: 18 non-pregnant
      healthy Katjang does aged 2-year-old were divided randomly into two groups. The
      first and second group consists of nine non-pregnant does each and the two groups
      were subdivided into three subgroups. The first group was experimentally
      inoculated with 1 ml of 10(7)cfu of live C. pseudotuberculosis through
      intradermal route, whereas the second group was inoculated with 1 ml phosphate
      buffer saline (pH 7) solution intradermally. The first group were further
      subdivided into three subgroups where, the first subgroup (B1) were kept for 30
      days post-infection, second subgroup (B2) were kept for 60 days post-infection,
      and third subgroup (B3) were kept for 90 days. The second group was further
      subdivided into three subgroups (C1, C2, and C3) where they were kept for 39, 60,
      and 90 days post-infection, respectively. RESULTS: From this study, there was
      successful isolation of C. pseudotuberculosis from the reproductive organs of the
      treatment group after 60 days post-infection. The subgroups (B1, C1, C2, and C3)
      did not show any presence of the causative organism in the reproductive organs.
      The second subgroup B2 and third subgroup B3 showed positive isolation of the
      causative organisms from the ovary, uterine horns, uterus, cervix, vagina, and
      inguinal lymph node of the experimental non-pregnant does. CONCLUSION: This study
      showed that chronic infection of C. pseudotuberculosis via intradermal route may
      cause effect toward the reproductive organs and may be able to influence the
      reproductive efficiency of the infected animals.

PMID- 27047178
TI  - Identifying factors affecting age at first semen freezing and age at first semen
      use in Sahiwal bulls.
AB  - AIM: The objective of the study was to evaluate the effects of non-genetic
      factors on reproduction traits viz. age at first semen freezing and age at first
      semen use of breeding bulls in Sahiwal bulls by fitting least-squares analysis.
      MATERIALS AND METHODS: The information on reproduction traits of 43 Sahiwal
      breeding bulls belonging to 8 sets of Sahiwal breeding program at Indian Council
      of Agricultural Research-National Dairy Research Institute (ICAR-NDRI), Karnal
      (Haryana), India during 27 years (1987-2013) were analyzed using fixed linear
      model. The information was collected from AI records, reproduction sheets, and
      bull AI register maintained at different sections of Institute viz. record room
      of Dairy Cattle Breeding Division (DCB), Cattle Yard, Artificial Breeding
      Research Centre, ICAR-NDRI, Karnal. RESULTS: The average age at first semen
      freezing and age at first semen use of Sahiwal breeding bulls was estimated as
      3.17+/-0.01 years and 5.35+/-0.01 years, with the coefficient of variation 18.93%
      and 20%, respectively. The overall least-squares mean for age at first semen
      freezing and age at first semen use was estimated as 3.14+/-0.09 years and 5.25+/
      0.02 years, respectively, in Sahiwal breeding bulls. Period of freezing/use had
      significant effects on reproductive traits (p<0.01). Season had no significant
      effect on any of the traits considered in this study. CONCLUSION: It can be
      concluded that management inputs such as nutrition, breeding, and optimum
      environment should be taken care of to optimize age at first semen freezing and
      age at first semen use for better utilization of superior germplasm.

PMID- 27047179
TI  - Genetic polymorphisms within exon 3 of heat shock protein 90AA1 gene and its
      association with heat tolerance traits in Sahiwal cows.
AB  - AIM: The present study was undertaken to identify novel single nucleotide
      polymorphism (SNP) in Exon 3 of HSP90AA1 gene and to analyze their association
      with respiration rate (RR) and rectal temperature (RT) in Sahiwal cows. MATERIALS
      AND METHODS: The present study was carried out in Sahiwal cows (n=100) with the
      objectives to identify novel SNP in exon 3 of HSP90AA1 gene and to explore the
      association with heat tolerance traits. CLUSTAL-W multiple sequence analysis was
      used to identify novel SNPs in exon 3 of HSP90AA1 gene in Sahiwal cows. Gene and
      genotype frequencies of different genotypes were estimated by standard procedure
      POPGENE version 1.32 (University of Alberta, Canada). The significant effect of
      SNP variants on physiological parameters, e.g. RR and RT were analyzed using the
      General Linear model procedure of SAS Version 9.2. RESULTS: The polymerase chain
      reaction product with the amplicon size of 450 bp was successfully amplified,
      covering exon 3 region of HSP90AA1 gene in Sahiwal cows. On the basis of
      comparative sequence analysis of Sahiwal samples (n=100), transitional mutations
      were detected at locus A1209G as compared to Bos taurus (NCBI GenBank
      AC_000178.1). After chromatogram analysis, three genotypes AA, AG, and GG with
      respective frequencies of 0.23, 0.50, and 0.27 ascertained. RR and RT were
      recorded once during probable extreme hours in winter, spring, and summer
      seasons. It was revealed that significant difference (p<0.01) among genetic
      variants of HSP90AA1 gene with heat tolerance trait was found in Sahiwal cattle.
      The homozygotic animals with AA genotype had lower heat tolerance coefficient
      (HTC) (1.78+/-0.04(a)), as compared to both AG and GG genotypes (1.85+/-0.03(b)
      and 1.91+/-0.02(c)), respectively. The gene and genotype frequencies for the
      locus A1209G were ascertained. CONCLUSIONS: Novel SNP was found at the A1209G
      position showed all possible three genotypes (homozygous and heterozygous).
      Temperature humidity index has a highly significant association with RR, RT, and
      HTC in all the seasons. Perusal of results across different seasons showed the
      significant (p<0.01) difference in RR, RT, and HTC among winter, spring, and
      summer seasons. Genetic association with heat tolerance traits reveals their
      importance as a potential genetic marker for heat tolerance traits in Sahiwal
      cows.

PMID- 27047180
TI  - Effect of Phyllanthus amarus on serum biochemical changes in azaserine induced
      pancreatic cancer in Wistar rats.
AB  - AIM: The present study was performed to investigate the effect of Phyllanthus
      amarus extracts on serum biochemical changes in azaserine induced pancreatic
      cancer in Wistar rats. MATERIALS AND METHODS: Pancreatic cancer was developed in
      Wistar rats by intraperitoneal administration of azaserine (cancer inducer) for
      21 days at the concentration of 5 mg/kg body weight. Aqueous and alcoholic
      extracts were given to rats of different groups as per protocol. RESULTS: The
      results data revealed that oral administration of P. amarus extracts had a
      significant change in pancreatic amylase, lipase, aspartate aminotransferase,
      alanine aminotransferase, and alkaline phosphatase activity. CONCLUSION: We
      concluded that extract of P. amarus possessed chemoprotective activity against
      azaserine induced pancreatic cancer in Wistar rats.

PMID- 27047181
TI  - Diversity of Eimeria spp. in dairy cattle of Guwahati, Assam, India.
AB  - AIM: To determine the prevalence and diversity of Eimeria spp. in dairy cattle
      present in and around Guwahati, Kamrup district, Assam, India. MATERIALS AND
      METHODS: A total of 2339 fecal samples of calves (535), heifer (641) and adult
      (1163) cattle were screened for 1 year present in and around Guwahati, Assam for
      detection of Eimeria oocysts by flotation techniques. Sporulation of the oocyst
      was done in 2.5% potassium dichromate solution for identification of the Eimeria
      species. RESULTS: Examination of fecal samples revealed an overall prevalence of
      11.97% Eimeria infection in dairy cattle of Guwahati, Assam. Age-wise, 33.2%,
      45.4%, and 21.4% infections were recorded in calves (<1 year), heifer (1-3 years)
      and adult (>3 years) cattle, respectively. Season-wise, infection was recorded
      highest during post-monsoon (16.29%), followed by monsoon (15%), winter (9.44%),
      and pre-monsoon (7.49%) season. Seven species of Eimeria were recorded viz.
      Eimeria bovis, Eimeria zuernii, Eimeria subspherica, Eimeria bukidnonensis,
      Eimeria auburnensis, Eimeria ellipsoidalis and Eimeria alabamensis. The oocyst
      count per gram of feces ranged from 50 to 1500 in infected cattle. CONCLUSION:
      This study indicates that there is the prevalence of seven species of Eimeria in
      dairy cattle of Guwahati, Assam and mostly prevalent during the post-monsoon
      season.

PMID- 27047182
TI  - Zoonotic enteric parasites transmitted from dogs in Egypt with special concern to
      Toxocara canis infection.
AB  - AIM: This work aimed to study the role played by dogs in transmitting zoonotic
      enteric parasites to humans in Egypt and to analyze the risk factors associated
      with the occurrence of such infection in dogs. Serodiagnosis of anti-Toxocara
      immunoglobulin G (IgG) antibodies among human beings as well as analyzing risk
      factors predispose to Toxocara canis infection in human beings are another
      objectives of this study. MATERIALS AND METHODS: From June to December 2013, a
      total of 130 fecal samples from 4 dog populations (Military, nomadic and
      domiciled dogs from rural and high standard districts) and 150 stool samples of 6
      occupational groups were examined for the presence of enteric parasitic
      infection. Moreover, 150 serum samples were collected from humans from whom stool
      samples were collected and examined for the presence of anti-T. canis antibodies.
      RESULTS: Enteric parasites were detected in 30% of fecal samples from 4 dog
      populations in Egypt. High infectivity had been reported in nomadic dogs (63.33%)
      (Crude odds ratios [COR]=67.36, 95% confidence interval [CI]=8.09-560.8,
      p<0.000), followed by domiciled dogs from rural areas (40%) (COR=26, 95% CI=3.14
      215.54, p=0.003), domiciled dogs from high standard areas (23.33%) (COR=11.87,
      95% CI=1.37-102.69, p=0.025) and military dogs (2.5%). Twelve species of enteric
      parasites were identified, Ancylostomatidae (6.15%), T. canis and Cryptosporidium
      spp. (5.38%, each), Heterophyes spp. (3.85%), Toxocara leonina and Blastocystis
      spp. (3.07%), Taenidae eggs (2.31%), Hymenolepis diminuta (1.54%) and Entamoeba
      canis, Cyclospora cayetanensis, and Paragonimus spp. (0.77%, each). Univariate
      logestic regression revealed significant association of age (COR=4.73, 95%
      CI=2.13-10.53, p<0.000), gender (COR=2.63, 95% CI=1.22-5.68, p<0.014), housing
      system (COR=5.10, 95% CI=2.04-12.75), p<0.000) with enteric parasitic infection
      in dogs. However, breeds (COR=6.91, 95% CI=0.88-54.52, p=0.067) and type of
      feeding (COR ranged from 3.5 to 7.62, p>0.05) did not seem to have a significant
      association among the examined dogs. Enteric parasitic infection was reported in
      31/150 human stools (20.67%). Students were the most affected groups (37.14%),
      followed by nomadic people (24%), house wives (20%), house guarders and military
      workers (12%, each), and employees (10%). The identified parasites were
      Cryptosporidium spp. (9.33%), Ascaris lumbercoides (3.33%), Heterophyes spp. and
      Ancylostoma spp. (2.66%, each) and Paragonimus spp. and Hymenolepis nana (1.33%,
      each). Toxocara IgG antibodies were detected in 36/150 (24%) serum samples
      investigated. Toxocara IgG antibodies were more prevalent in males (26.66%) than
      females (20%). Seroprevalence was highest (17/35, 48.57%) in 7-15 years old
      (COR=6.93, 95% CI=1.75-27.43, p=0.006). Seroprevalence values for T. canis
      antibodies were higher in those; raising dogs (29.85%), eating raw vegetables
      (25.21%) and not washing hands before meals (25.45%). T. canis antibodies were
      detected in 25% of those contacted with soil compared to 30% of those did not.
      Students were mostly affected (34.29%), followed by nomadic people (32%), house
      guarders (28%), housewives (20%), military workers (13%), and employees (10%).
      CONCLUSION: Detection of enteric parasites in dogs and humans in Egypt
      substantiates the role posed by dogs in transmitting zoonotic parasites to humans
      and knock an alarm for common sources of infection for humans and dogs. Common
      sources may be infected fish or contaminated vegetables that are consumed by dogs
      or humans or even infected rodents that may contaminate their feed. This pilot
      study necessitate the need for similar studies and tracing such infection in
      fish, vegetables, rodent that may be responsible for infecting humans and dogs in
      order to understand the epidemiology of zoonotic parasitic infection transmitted
      from dogs to humans.

PMID- 27047183
TI  - Tissue reactivity and suture handling characteristics of "jimat" against silk and
      chromic gut in cat thigh muscle: A comparative study.
AB  - AIM: This study was conducted to evaluate and compare the tissue reactivity and
      suture handling characteristics of chromic gut, silk, and 'jimat' suture
      materials in cat thigh muscle. MATERIALS AND METHODS: This experimental study was
      conducted from November, 2013 to April, 2014 in Kombolcha Animal Diseases Survey,
      Research and Diagnostic Laboratory, Kombolcha, Ethiopia. A total of 36 local
      breed male cats were randomly assigned into chromic gut, silk, and "jimat" groups
      of 12 cats each as A, B, and C, respectively. The hind leg muscle biceps femoris
      was incised and sutured with suture materials according to their groups. The
      muscle samples with its suture were collected at six different days interval i.e.
      1, 3, 7, 14, 21, and 28 and processed histopathologically to assess the degree of
      leukocytic infiltration and fibrous and granulation tissue formation (GTF). In
      addition, all suture materials were evaluated intraoperatively about their
      handling characteristics, by rating the precision of knot tying, square knot
      positioning, and resistance to knot slippage. The statistical analysis was done
      with two-way ANOVA, Kruskal-Wallis, and Chi-square tests. RESULTS: The
      histopathology showed that "jimat" thread (2.4+/-1.2) had produced least
      leukocytic infiltration than chromic gut (4.5+/-1.9) and silk (4.3+/-1.5) sutures
      during the study period. Higher GTF was seen at day 3 (6 [100%]), 7 (6 [100%])
      and day 14 (4 [66.7%]) in all sutures, whereas "jimat" showed significantly
      (p<0.05) higher fibrous tissue formation (10 [83.3%]) than others. Moreover,
      "jimat" suture had equal suture handling characteristics (p>0.05) with both
      chromic gut and silk. CONCLUSION: The result indicated that a single strand
      "jimat" thread appears to be the most satisfactory suture material as regards to
      both tissue reaction and suture handling characteristics for skeletal muscle
      approximation in cats and provided that studies on its carcinogenic effects
      should be done.

PMID- 27047184
TI  - Microsatellite based genetic diversity study in indigenous chicken ecotypes of
      Karnataka.
AB  - AIM: The current study was the first of its kind taken upon indigenous ecotypes
      of the Karnataka in order to unravel the diversity details at 20 chicken
      microsatellite regions. MATERIALS AND METHODS: 210 indigenous chicken belonging
      to six districts of Bangalore and Mysore division formed the target sample for
      the present study. The genomic deoxyribonucleic acid was isolated by phenol
      chloroform isoamyl alcohol method. A panel of 20 microsatellite regions,
      including 14 recommended by FAO and six identified from published scientific
      literature became the targeted chicken genomic region. 27-33 samples were
      successfully genotyped in each of the six ecotypes through simplex or multiplex
      polymerase chain reactions, polyacrylamide gel electrophoresis and silver
      staining for the selected microsatellite panel. RESULTS: The chickens of
      Ramanagara and Chamrajnagara were most distant with a Nei's genetic distance
      value of 0.22. The chickens of Bangalore rural and Mysore were least distant with
      a value of 0.056. The Ramanagara and Chamrajnagara pair had Nei's genetic
      identity value of 0.802, which is least among all pairs of ecotypes. There were
      five main nodes from which the six ecotypes evolved on the basis 20
      microsatellite markers used in this study. This study indicates that the four
      ecotypes Ramnagara, Bangalore Rural, Chickaballapura and Mysore are genetically
      identical due to their common ancestral evolution while, Mandya and Chamrajnagara
      ecotypes formed a relatively different cluster due to a separate common ancestral
      chicken population and less number of generations since drifting from bifurcation
      node. CONCLUSION: Twenty microsatellite markers based genetic diversity study on
      six indigenous ecotypes indicated lower genetic distances as well as lower FST
      values compared to the distinguished breeds reported. There were two main
      clusters, which differentiated into six ecotypes. They may differentiate into
      more distinct varieties if bred in isolation for a longer number of generations.

PMID- 27047185
TI  - Evaluation of seasonal changes of serum and plasma estradiol-17beta, progesterone
      and testosterone in dolphins (Tursiops truncatus) by chemiluminescence.
AB  - AIM: The purpose of the research was to test and validate an innovative and safe
      chemiluminescence method to evaluate sexual hormones in serum and plasma samples
      of Tursiops truncatus. MATERIALS AND METHODS: The research was performed on 9
      bottlenose dolphins entertained in Oltremare and in Zoomarine aquatic parks,
      sampled by the tail vein or from the ventral one and an ultrasound monitoring,
      throughout a 6 months period. Blood samples were analyzed using a
      chemiluminescence method. Data obtained were compared to radioimmunoassay and
      enzyme immuno assay reference data, with the purpose to test and validate this
      method, through the calculation of the coefficient of variability, and its
      reliability on serum and plasma samples. A one-way analysis of variance was
      applied to test the effect of time on serum and plasma hormonal changes. RESULTS:
      Mean concentrations of estradiol-17beta in serum were equal to 149.07+/-6.82
      pmol/L, and in plasma equal to 159.14+/-12.99 pmol/L; mean values of progesterone
      in serum were equal to 0.69+/-0.05 pmol/L, and in plasma equal to 0.64+/-0.05
      pmol/L; mean values of testosterone in serum were equal to 44.43+/-14.42 nmol/L,
      and in plasma equal to 48.99+/-11.20 nmol/L. CONCLUSION: It would be interesting
      to widen the investigations on a larger number of subjects, in which the
      relationship between the concentrations of free and binding steroid hormones,
      with the dosing of binding proteins, would define the physiological ranges of
      reference in the T. truncatus.

PMID- 27047186
TI  - Comparison of follicular dynamics, superovulatory response, and embryo recovery
      between estradiol based and conventional superstimulation protocol in buffaloes
      (Bubalus bubalis).
AB  - AIM: To evaluate the follicular dynamics, superovulatory response, and embryo
      recovery following superstimulatory treatment initiated at estradiol-17beta
      induced follicular wave emergence and its comparison with conventional
      superstimulatory protocol in buffaloes. MATERIALS AND METHODS: Six normal cycling
      pluriparous buffaloes, lactating, 90-180 days post-partum, and weighing between
      500 and 660 kg were superstimulated twice with a withdrawal period of 35 days in
      between two treatments. In superstimulation protocol-1 (estradiol group)
      buffaloes were administered estradiol-17beta (2 mg, i.m.) and eazibreed
      controlled internal drug release (CIDR) was inserted intravaginally (day=0) at
      the random stage of the estrous cycle. On the day 4, buffaloes were
      superstimulated using follicle stimulating hormone (FSH) 400 mg, divided into 10
      tapering doses given at 12 hourly intervals. Prostaglandin F2alpha analogs
      (PGF2alpha) was administered at day 7.5 and day 8, and CIDR was removed with the
      second PGF2alpha injection. In superstimulation protocol - 2 (conventional group)
      buffaloes were superstimulated on the 10(th) day of the estrous cycle with same
      FSH dose regimen and similar timings for PGF2alpha injections. In both groups,
      half of the buffaloes were treated with luteinizing hormone (LH) 25 mg and other
      half with 100 ug buserelin; gonadotrophin releasing hormone (GnRH) analog at 12 h
      after the end of FSH treatment. All buffaloes in both protocols were inseminated
      twice at 12 and 24 h of LH/GnRH treatment. Daily ultrasonography was performed to
      record the size and number of follicles and superovulatory response. RESULTS:
      Significantly higher number of small follicles (<8 mm) was present at the time of
      initiation of superstimulatory treatment in the estradiol group compared to the
      conventional group (12.5+/-0.80 vs. 7.3+/-1.21, respectively, p=0.019), however,
      the number of ovulatory size follicles (>=8 mm) did not differ significantly
      between the respective groups (15.5+/-1.24 vs. 12.2+/-1.30; p=0.054). Total
      embryos and transferable embryos recovered were non-significantly higher in the
      estradiol group compared to the conventional group (5.83+/-0.86 vs. 4.67+/-1.16,
      p=0.328, and 3.67+/-0.93 vs. 2.67+/-0.68, p=0.437, respectively). The significant
      higher proportion of transferable embryos were recovered in buffaloes treated
      with LH compared to GnRH (73.3% vs. 48.5%; p=0.044). CONCLUSION: The average
      number of ovulatory size follicles (>8 mm), corpora lutea, and transferable
      embryos was higher in buffaloes superstimulated at estradiol-induced follicular
      wave compared to the conventional protocol: Further the percentage of
      transferable embryos was significantly higher in buffaloes administered with LH
      compared to GnRH.

PMID- 27047187
TI  - Association of milk components with intra-mammary inflammation in Jaffrabadi
      buffaloes.
AB  - AIM: To study the alteration of major milk components such as milk fat, protein,
      lactose, solid not fat (SNF) and total solids (TS) and their association with
      different degree of intra-mammary inflammation (IMI) in Jaffrabadi buffaloes.
      MATERIALS AND METHODS: Milk samples (n=1516) were collected from Jaffrabadi
      buffaloes separately from each quarter. Milk samples were analyzed for milk fat,
      protein, lactose, SNF and TS percent on the same day using milk analyzer
      "LACTOSCAN." Milk samples were checked for IMI by California mastitis test (CMT),
      and the results were expressed as negative (0), +, ++, and +++ CMT score. The
      traits of milk components which showed significant difference (p<0.05) between
      samples from inflamed and non-inflamed quarters were analyzed by receiver
      operating characteristic (ROC) analysis to see the accuracy and degree of
      association with IMI. RESULTS: Among several milk components, milk protein and
      lactose percent showed a significant difference (p<0.05) between milk samples
      from normal and inflamed quarters. Though, during the early stage of mammary
      gland inflammation milk protein percent remained significantly high (p<0.05),
      later with an increase in the degree of severity of inflammation it did not show
      any difference. Milk samples from normal udder quarters had significantly higher
      lactose percent than inflamed quarters (p<0.05). Milk lactose percent decreased
      gradually with an increase in the degree of severity of inflammation. ROC
      analysis revealed that milk samples having lactose content below the threshold
      values had significantly higher chances to come from inflamed udder quarters
      (p<0.05). Though, the value of the area under curve (AUC) indicated that milk
      lactose was significantly associated with IMI (p<0.05), the accuracy was moderate
      (AUC=0.71-0.75). CONCLUSIONS: The results of the present study indicated that
      milk lactose percent gradually and significantly reduced during IMI and can be
      used as a marker for identification of IMI in buffaloes. However, ROC analysis
      further confirmed that using milk lactose IMI can be identified with moderate
      accuracy.

PMID- 27047188
TI  - Genetic diversity and phylogenetic relationships in local cattle breeds of
      Senegal based on autosomal microsatellite markers.
AB  - AIM: In Senegal, uncontrolled cross-breeding of cattle breeds and changes in
      production systems are assumed to lead to an increase of gene flow between
      populations. This might constitute a relevant threat to livestock improvement.
      Therewith, this study was carried out to assess the current genetic diversity and
      the phylogenetic relationships of the four native Senegalese cattle breeds (Gobra
      zebu, Maure zebu, Djakore, and N'Dama). METHODS: Genomic DNA was isolated from
      blood samples of 120 unrelated animals collected from three agro-ecological areas
      of Senegal according to their phenotypic traits. Genotyping was done using 11
      specific highly polymorphic microsatellite makers recommended by Food and
      Agriculture Organization. The basic measures of genetic variation and
      phylogenetic trees were computed using bioinformatics' software. RESULTS: A total
      of 115 alleles were identified with a number of alleles (Na) at one locus ranging
      from 6 to 16. All loci were polymorphic with a mean polymorphic information
      content of 0.76. The mean allelic richness (Rs) lay within the narrow range of
      5.14 in N'Dama taurine to 6.10 in Gobra zebu. While, the expected heterozygosity
      (HE) per breed was high in general with an overall mean of 0.76+/-0.04.
      Generally, the heterozygote deficiency (FIS) of 0.073+/-0.026 was relatively due
      to inbreeding among these cattle breeds or the occurrence of population
      substructure. The high values of allelic and gene diversity showed that
      Senegalese native cattle breeds represented an important reservoir of genetic
      variation. The genetic distances and clustering trees concluded that the N'Dama
      cattle were most distinct among the investigated cattle populations. So, the
      principal component analyses showed qualitatively that there was an intensive
      genetic admixture between the Gobra zebu and Maure zebu breeds. CONCLUSIONS: The
      broad genetic diversity in Senegalese cattle breeds will allow for greater
      opportunities for improvement of productivity and adaptation relative to global
      changes. For the development of sustainable breeding and crossbreeding programs
      of Senegalese local breeds, effective management is needed towards genetic
      selection and transhumance to ensure their long-term survival.

PMID- 27047189
TI  - Evaluation of recombinant outer membrane protein C based indirect enzyme-linked
      immunoassay for the detection of Salmonella antibodies in poultry.
AB  - AIM: To evaluate the efficacy of recombinant outer membrane proteinC (rOmpC)
      based enzyme-linked immunoassay (ELISA) for the diagnosis of salmonellosis in
      poultry. MATERIALS AND METHODS: Three antigens were prepared, and the indirect
      ELISA was standardized using the antigens and the antiserum raised in chicken
      against Omp and rOmpC. Sera were collected from a total of 255 apparently healthy
      field chickens and screened for the presence of Salmonella antibodies by this
      ELISA. RESULTS: The sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analysis of Omp revealed major polypeptides at 36, 42 and 52 kDa, and the rOmpC
      was evident by a single protein band of 43 kDa. The Omp and rOmpC antigen
      revealed an optimum concentration of 78 and 156 ng, respectively, in the assay,
      while the whole cell antigen gave an optimum reaction at a concentration of 10(6)
      organisms/ml. The test was found to be specific as it did not react with any of
      the antisera of seven other organisms. The developed ELISA detected Salmonella
      antibodies from 22 (8.62%) samples with rOmpC antigen, while 24 (9.41%) samples
      gave a positive reaction with both Omp and whole cell antigens. CONCLUSION: We
      suggest rOmpC based indirect ELISA as a suitable screening tool for serological
      monitoring of poultry flocks.

PMID- 27047191
TI  - Pathomorphological and microbiological studies in sheep with special emphasis on
      gastrointestinal tract disorders.
AB  - AIM: The present study was envisaged to elucidate the pathomorphological and
      microbiological aspects of gastrointestinal tract (GIT) disorders of sheep/lambs.
      MATERIALS AND METHODS: Samples for research were collected from 12 sheep died
      with a history of GIT disorders which were brought for post-mortem examination to
      the Department of Veterinary Pathology, Lala Lajpat Rai University of Veterinary
      and Animal Sciences, Hisar, for pathomorphological and microbiological
      examination. RESULTS: Gross pathological changes in various organs noticed were
      abomasitis, congestion and hemorrhages in intestine; necrotic foci on liver
      surface; enlarged, hard, and indurated mesenteric lymph nodes, hydropericardium,
      congestion, hemorrhages and consolidation of lungs and congestion and soft
      kidneys as the major change. On histopathological examination, there were
      abomasitis with leukocyte infiltration, enteritis with desquamation of mucosal
      epithelium and goblet cell hyperplasia, lymphadenitis with depletion of
      lymphocytes in the germinal center of lymphoid follicle, and splenitis with
      depletion of lymphocytes in the white pulp. In the liver congestion, degenerative
      changes in hepatocytes including cloudy swelling, fatty changes, congestion in
      sinusoids, and dilatation of sinusoids leading to atrophy of hepatocytes. Lungs
      evidenced edema, congestion, emphysema, serous inflammation, thickening of
      interlobular septa, fibrinous pleuritis, and peribronchiolar lymphoid follicle
      formation. Heart revealed sarcocystosis, fibrinous pericarditis, and
      hyalinization of the myocardium. In kidneys, congestion, focal interstitial
      nephritis, hyaline degeneration, and coagulative necrosis were seen. For
      microbiological aspects; cultural isolation was done from samples of liver,
      abomasum, mesenteric lymph nodes, spleen, heart blood, lungs, and kidneys from
      the carcasses of sheep/lambs. Escherichia coli was the only bacterium isolated
      during present studies. E. coli isolates from different tissues of carcasses of
      sheep/lambs were subjected to in-vitro drug sensitivity testing. Ciprofloxacin,
      cefixime, polymyxin B, amoxicillin + sulbactam, and amoxicillin + clavulanic acid
      were the most sensitive drugs followed by amikacin, ofloxacin, ampicillin, co
      trimoxazole, and amoxicillin. CONCLUSIONS: From the present study, it is
      reasonable to conclude that the major etiopathological cause of GIT disorders in
      sheep was E. coli infection, which causes a pathomorphological effect on various
      cadaver organs viz. abomasum, intestine, liver, mesenteric lymph nodes, lungs,
      spleen, kidneys, and heart followed by parasitic infection of Haemonchus
      contortus.

PMID- 27047190
TI  - Histology and scanning electron microscopy of the tubal tonsil of goats.
AB  - AIM: To observe the light and scanning electron microscopy (SEM) of the caprine
      tubal tonsil. MATERIALS AND METHODS: The study was conducted on six crossbred
      male goats of 6 months of age. From the median sections of the head, tissue
      pieces from the nasopharynx around the auditory tube were collected and fixed for
      histology and SEM. RESULTS: Tonsillar lymphoid tissue was located in the
      nasopharynx ventral to the auditory tube opening in the lateral wall of the
      pharynx. The height of the surface epithelium of the tubal tonsil measured
      80.17+/-1.08 um and was a pseudostratified ciliated columnar type with basal,
      supporting, and goblet cells. Above the dome of lymphoid nodules, the epithelium
      was modified into a follicle associated epithelium (FAE), also called lympho
      epithelium or reticular epithelium and was characterized by the absence of goblet
      cells and cilia, reduced number of cell layers, and a large number of lymphoid
      cells due to interrupted basement membrane. The height of FAE was smaller than
      that of the surface epithelium and measured 34.33+/-0.92 um. The surface of tubal
      tonsil showed folds and invaginations, which formed crypts. The lamina propria
      submucosa underneath the epithelium was formed by the meshwork of reticular and,
      thin and loose collagen fibers with dome-like accumulation of lymphoid nodules.
      In the secondary lymphoid nodules, a corona, parafollicular area, and
      interfnodular area were observed. The average number of lymphoid nodules counted
      per field under low power magnification of microscope was 1.17+/-0.17, and the
      internodular distance was 34.00+/-4.37 um. The mean diameter of lymphoid nodules
      was 566.67+/-11.45 um and the lymphocyte count per nodule was 14741.67+/-174.36.
      The number of plasma cells counted per field under low power was 44.38+/-2.90
      below the surface epithelium. The tubal tonsil was not encapsulated. In SEM, the
      surface epithelium of the tubal tonsils presented ciliated cells, microvillus
      (MV) cells, and goblet cells. The region of FAE possessed Type-I and Type-II MV
      cells and microfold (M) cells in between. CONCLUSION: It was concluded that the
      tubal tonsils were well developed in goats, which might serve as a means of
      protection against the spread of infection to the middle ear cavity.

PMID- 27047192
TI  - Effect of replacing oat fodder with fresh and chopped oak leaves on in vitro
      rumen fermentation, digestibility and metabolizable energy.
AB  - AIM: A study was conducted to evaluate the effect of replacing oat fodder (OF)
      with fresh oak leaves (FOL) or chopped oak leaves (COL) on rumen fermentation and
      digestibility through in vitro gas production technique (IVGPT). MATERIALS AND
      METHODS: Nine different diets were prepared by mixing OF with oak leaves (either
      FOL or COL) in different ratios (100:0, 75:25, 50:50, 25:75, and 0:100). The
      rations were evaluated through Hohenheim IVGPT with 200 mg substrate and 30 ml of
      buffered rumen liquor. All the syringes were incubated at 39 degrees C for 24 h
      in buffered rumen liquor of cattle. After 24 h, the total gas production was
      recorded, and the contents were analyzed for in vitro methane production,
      protozoa no. and ammonia-N. RESULTS: Chopping (p<0.01) reduced the tannin
      fractions as well as non-tannin phenol. Increase in levels of oak decreased total
      gas production, methane, organic matter (OM) digestibility, and metabolizable
      energy (ME) values. The polyphenol content of the substrate did not show any
      significant difference on the protozoal count. CONCLUSION: In vitro studies
      revealed that the addition of oak leaves reduced the methane production and
      ammonia nitrogen levels; however, it also decreased the OM digestibility and ME
      values linearly as the level of the oak leaves increased in the diet. Chopping
      was effective only at lower inclusion levels. Further studies, especially in vivo
      studies, are needed to explore the safe inclusion levels of oak leaves in the
      diet of ruminants.

PMID- 27047194
TI  - Genetic analysis of reproductive performance of Frieswal cattle at Military Farm,
      Ambala.
AB  - AIM: This study was carried out to investigate the genetic analysis of
      reproductive performance of Frieswal cattle at Military Farm, Ambala. MATERIALS
      AND METHODS: A total number of 3005 lactation records of 1147 Frieswal cows over
      a period of 15 years extending from 1993 to 2007 were used to study at Military
      Dairy Farm, Ambala. The study period was divided into 5 period of 3 years each.
      The average performances of reproduction traits, effect of genetic and non
      genetic factors were analyzed, and estimation of genetic and phenotypic
      parameters of reproduction traits was undertaken. RESULTS: The age at first
      calving (AFC) differed significantly across the periods of calving. The AFC was
      lowest during the third period (1999-2001) and longest in the first period (1993
      95). The effect of season and period of calving, lactation order and regression
      of AFC on dry period, calving interval and service period was highly significant.
      The effect of sire was non-significant. The heritability estimates were low for
      almost all the traits under study. The service period had a high genetic
      correlation with dry period and calving interval. The dry period also found to
      have a low genetic correlation with calving interval in Frieswal cows. Service
      period had a high phenotypic correlation with dry period and very high with a
      calving interval. The phenotypic correlation between the dry period and calving
      interval was recognized high. CONCLUSIONS: Low heritability estimate for the
      reproduction traits indicates that there is a very little additive genetic
      variance in these traits, and individual selection will not be helpful for
      improving them. Improvement may be brought through better feeding and management
      of cows by reducing the environmental variability.

PMID- 27047193
TI  - Effect of glutamine supplementation and replacement of tris-egg yolk based
      extender with defatted cow milk on spermatozoa quality after equilibration and
      thawing.
AB  - AIM: The present study was designed to evaluate the effect of supplementation of
      glutamine and replacement of Tris-egg yolk (TE) based buffer with defatted cow
      milk on the spermatozoa quality after equilibration and thawing. MATERIALS AND
      METHODS: Semen was collected from five Bhadawari bulls biweekly, and a total of
      30 ejaculates were taken. The semen ejaculates were pooled and divided into three
      equal parts. The pooled semen was diluted by TE based extender (control), TE +
      glutamine (8 mM) (T1) and 50% TE + 50% deffated cow milk + glutamine (8 mM) (T2).
      At two stages viz. after equilibration and after 12 h of cryopreservation (thawed
      samples), progressive motility, percent live, and percent acrosomal damage of the
      spermatozoa was assessed. RESULTS: Supplementation of glutamine improved (p<0.05)
      the spermatozoa quality with respect to the progressive motility, percent live
      and acrosomal damage both post-equilibration and post-thaw. T2 improved (p<0.05)
      the spermatozoa quality as compared to control, however; it was less (p<0.05)
      effective as compared T1 both post-equilibration and post-thaw. CONCLUSION: From
      the results of present study it can be concluded that glutamine supplementation
      was effective in maintaining post-equilibration and post-thaw spermatozoa quality
      whereas defatted cow milk was not as effective as TE based buffer in the extender
      in improving the spermatozoa quality.

PMID- 27047195
TI  - Experimental infection of Aphanomyces invadans and susceptibility in seven
      species of tropical fish.
AB  - AIM: Epizootic ulcerative syndrome (EUS) causes by aquatic oomycete fungus,
      Aphanomyces invadans is a dangerous fish disease of a wide range of fresh and
      brackish water, wild and farmed fish throughout the world. The objective of the
      present study was to determine the susceptibility of a number of tropical fish
      species to the EUS and compare the severity of infection between experimental
      groups. MATERIALS AND METHODS: Snakehead, Channa striata (Bloch, 1793); snakeskin
      gourami, Trichopodus pectoralis (Regan, 1910); koi carp, Cyprinus carpio
      (Linnaeus, 1758); broadhead catfish, Clarias macrocephalus (Gunther, 1864);
      goldfish, Carassius auratus (Linnaeus, 1758); climbing perch, Anabas testudineus
      (Bloch, 1792); and Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) were
      challenged by intramuscular injection using zoospores of Aphanomyces invadans
      (NJM9701). The infected fish skins and muscles were examined for EUS
      histopathological characteristics, and the results on the severity of lesions and
      mortality were analyzed using SPSS program. RESULTS: All zoospore-injected fish
      were shown to be susceptible to the EUS infection except Nile tilapia. Although,
      the general histopathological pattern was similar in the zoospore-injected group,
      but there were some variation in granulomatous reaction, that is the presence or
      absence of giant cells, and time of mortality were detected. The result of
      statistical analysis showed that there was a significant difference between
      species, (c (2)=145.11 and p<0.01). CONCLUSION: Gourami, koi carp, and catfish
      were demonstrated to be highly susceptible while goldfish and climbing perch were
      found to be moderately susceptible to the EUS infection. These findings suggested
      that the cellular response of fish to mycotic infection and granulomatous
      reaction varied in different fish species, which could not be an indicator of
      susceptibility or resistant to the EUS itself, although it was shown that the
      granulation rate and the level of maturity or solidification (consolidation of
      granulomas) were higher in resistant fish.

PMID- 27047196
TI  - Analysis of Reproductive Traits of Broiler Rabbits Reared in Sub-temperate
      Climate of Kodai Hills, Tamil Nadu, India.
AB  - AIM: The present study was carried out at Institute Rabbit Farm of Southern
      Regional Research Centre, Mannavanur, Kodaikanal, Tamil Nadu, India having sub
      temperate climate with winter temperature during night hours going below 0
      degrees C with an objective of finding the influence of different factors such as
      breed, year, season and parity on different reproductive traits of broiler
      rabbits in order to come out with the best strategies for improving the
      productivity. MATERIALS AND METHODS: A total of 1793 records (946 White Giant and
      847 Soviet Chinchilla) for weight at mating (WM), weight at kindling (WK),
      gestation length (GL), litter size at birth (LSB) and litter size at weaning
      (LSW), litter weight at birth (LWB), and litter weight at weaning (LWW) were
      collected in the period between 2000 and 2009 and the data was analyzed using
      general linear model option of SAS 9.2. RESULTS: The overall mean GL, WM, WK,
      LSB, LSW, LWB, and LWW were 31.68+/-0.04 days, 3.65+/-0.01 kg, 3.84+/-0.01 kg,
      6.91+/-0.08, 5.49+/-0.09, 387.62+/-4.07 g, and 4.66+/-0.07 kg, respectively. The
      breed has significantly influenced GL, WK, LSW, LWB, and LWW. The LSB, LSW, LWB,
      and LWW were 7.05+/-0.11, 5.76+/-0.13, 399.55+/-5.88 g, and 4.87+/-0.10 kg,
      respectively in White Giant and corresponding values for Soviet Chinchilla were
      6.78+/-0.11, 5.22+/-0.12, 375.91+/-5.64 g, and 4.46+/-0.09 kg, respectively. The
      year of kindling had significantly affected all the reproductive traits under
      study and is varying over different years. The parity significantly influenced
      the WM, WK, and LWW. The LWW increased from first (4.16+/-0.21 kg) to second
      parity (4.86+/-0.19 kg) and remained in the same range from third parity onward.
      WM was significantly higher in spring season (3.72+/-0.02) than the animals in
      rainy (3.59+/-0.02) and winter season (3.65+/-0.02). Better reproductive
      performance in terms of higher LSB, LSW, LWB, and LWW as observed in the present
      study might be due to conducive environmental conditions prevailing in the
      region. CONCLUSION: The significant effects of the non-genetic factors like year
      of kindling on all reproductive traits, season, and parity on some of the traits
      in rabbit breeds are indications that any future production enhancement strategy
      must take into consideration the environment by providing additional care, feed
      supplementation and better shelter management to the rabbits, so that the full
      genetic potential can be realized.

PMID- 27047197
TI  - Phenotypic and genotypic detection of virulence factors of Staphylococcus aureus
      isolated from clinical and subclinical mastitis in cattle and water buffaloes
      from different farms of Sadat City in Egypt.
AB  - AIM: To characterize Staphylococcus aureus from clinical and subclinical mastitis
      and identify virulence factors. MATERIALS AND METHODS: Two hundred and two milk
      samples were collected, 143 from mastitic cattle and buffaloes 94 and 49,
      respectively, and 59 from apparently healthy cattle and buffaloes 35 and 24,
      respectively. RESULTS: California mastitis test was applied and positive
      prevalence were 91.48% and 75.51% for cattle and buffalo with clinical mastitis
      and 37.14% and 45.83% for cattle and buffalo with subclinical mastitis. S. aureus
      was isolated from clinically mastitic cattle and buffaloes were 39.29% and 50%,
      respectively. While, from subclinical mastitic cattle and buffaloes were 80% and
      72.73%, respectively. Hemolytic activity was assessed for S. aureus isolated from
      clinically and subclinical mastitic cases with prevalences of 100% and 56.25%,
      respectively. Thermo nuclease production from clinically and subclinical mastitic
      cases was 25% and 56.25%, respectively. Simplex polymerase chain reaction (PCR)
      conducted on S. aureus using 16S rRNA, clumping factor A, Panton valentine
      leukocidin, coagulase (Coa), alpha-hemolysin and beta-hemolysin those proved
      existence in 100%, 46.9%, 65.6%, 100%, 34.4%, and 43.75% of the isolates,
      respectively. While, multiplex PCR is utilized for detection of enterotoxins and
      proved that 12.5% was positive for enterotoxine Type D. CONCLUSIONS: It is
      concluded that simplex and multiplex PCR assays can be used as rapid and
      sensitive diagnostic tools to detect the presence of S. aureus and characterize
      its virulence factors that help in detection of severity of infection,
      distribution and stating preventive and control strategies.

PMID- 27047198
TI  - Sequence-based comparative study of classical swine fever virus genogroup 2.2
      isolate with pestivirus reference strains.
AB  - AIM: This study was undertaken with the aim to compare and establish the genetic
      relatedness between classical swine fever virus (CSFV) genogroup 2.2 isolate and
      pestivirus reference strains. MATERIALS AND METHODS: The available complete
      genome sequences of CSFV/IND/UK/LAL-290 strain and other pestivirus reference
      strains were retrieved from GenBank. The complete genome sequence, complete open
      reading frame, 5' and 3' non-coding region (NCR) sequences were analyzed and
      compared with reference pestiviruses strains. Clustal W model in MegAlign program
      of Lasergene 6.0 software was used for analysis of genetic heterogeneity.
      Phylogenetic analysis was carried out using MEGA 6.06 software package. RESULTS:
      The complete genome sequence alignment of CSFV/IND/UK/LAL-290 isolate and
      reference pestivirus strains showed 58.9-72% identities at the nucleotide level
      and 50.3-76.9% at amino acid level. Sequence homology of 5' and 3' NCRs was found
      to be 64.1-82.3% and 22.9-71.4%, respectively. In phylogenetic analysis, overall
      tree topology was found similar irrespective of sequences used in this study;
      however, whole genome phylogeny of pestivirus formed two main clusters, which
      further distinguished into the monophyletic clade of each pestivirus species.
      CSFV/IND/UK/LAL-290 isolate placed with the CSFV Eystrup strain in the same clade
      with close proximity to border disease virus and Aydin strains. CONCLUSION:
      CSFV/IND/UK/LAL-290 exhibited the analogous genomic organization to those of all
      reference pestivirus strains. Based on sequence identity and phylogenetic
      analysis, the isolate showed close homology to Aydin/04-TR virus and distantly
      related to Bungowannah virus.

PMID- 27047199
TI  - Epidemiological studies on forestomach disorders in cattle and buffaloes.
AB  - AIM: To study epidemiology of forestomach (reticuloruminal, omasal, and abomasal)
      disorders in cattle and buffaloes. MATERIALS AND METHODS: The 106 buffaloes and
      32 cattle referred for treatment to the university large animals teaching
      hospital with the complaint of gastrointestinal diseases constituted the study
      material. The cases were diagnosed based on history, clinical examination,
      hematology, biochemistry, radiography, peritoneal fluid analysis and
      ultrasonography, rumenotomy, and postmortem. A questionnaire was prepared
      containing important information on housing, husbandry practices, including
      feeding practices and individual animal information viz. age, species, month of
      the year, parity, gestation (month), and recent parturition. The animals were
      divided into eight groups and analysis of variance was performed to study risk
      factors associated with each condition. RESULTS: The forestomach disorders are
      widely prevalent in cattle and buffaloes between April and October, during summer
      and rainy season (90%) and constituted a significant proportion of diseased cows
      and buffaloes (138/1840) at the hospital. Different forestomach disorders and
      their prevalence was: Diaphragmatic hernia (DH) 17%, traumatic
      reticuloperitonitis (TRP) 14%, idiopathic motility disorder or vagus indigestion
      (VI) 22%, adhesive peritonitis (AP) 13%, frank exudative peritonitis (FEP) 12%,
      reticular abscess (RA) 8%, ruminal and omasal impaction (RI) 5%, and abomaso
      duodenal ulceration (ADU) 9%. DH and RA were significantly more common in
      buffaloes as compared to cattle. Similarly, impactions were more in buffaloes but
      its incidence was very low (5%). ADU was present in buffalo as commonly as in
      cows. Exclusive feeding of wheat straw was present in an abysmally low number of
      animals and hence could not be considered the cause of these disorders. DH was
      significantly higher in buffaloes (>5 years) of 5-8 years of age and TRP, VI and
      AP were observed in cattle and buffalo of 2-8 years of age during the second half
      of gestation to 1 month post-calving. FEP (12%) occurred more commonly within 1
      month of parturition. CONCLUSIONS: DH, TRP, frank and AP and ADU are causes of
      the widely prevalent forestomach (reticuloruminal, omasal and abomasal) disorders
      in cattle and buffaloes.

PMID- 27047200
TI  - Serotypes, antimicrobial profiles, and public health significance of Salmonella
      from camels slaughtered in Maiduguri central abattoir, Nigeria.
AB  - AIM: This study aimed at determining the serotypes, antimicrobial profiles, and
      public health importance of Salmonella strains from camels slaughtered at
      Maiduguri central abattoir, Nigeria. MATERIALS AND METHODS: Two hundred samples
      were obtained from camel comprising of intestines, feces, liver, and spleen (n=50
      each). Non-lactose fermenting dark center Salmonella colonies were identified
      using standard biochemical techniques, serotyped and subjected to antimicrobial
      susceptibility test using minimum inhibition concentration method. RESULTS: Out
      of the 200 samples collected, 17 were Salmonella positive (spleen=7, intestine=6,
      feces=3, and liver=1) with a prevalence of 8.5%. Five serotypes comprising
      Salmonella Eko, 7 (3.5%), Salmonella Uganda, 4 (2.0%), Salmonella Amager, 2
      (1.0%), Salmonella Westhampton, 2 (1.0%), and Salmonella Give, 2 (1.0%) were
      incriminated. Majority of the serotypes were sensitive to the antimicrobials, but
      one Salmonella Amager exhibited resistance to streptomycin, and one each of
      Salmonella Uganda and Salmonella Eko were resistant to sulfamethoxazole.
      CONCLUSION: This study revealed the prevalence and the antibiotic resistance
      profile of newly emerging Salmonella from camels in the northeast of Nigeria,
      which can serve as a means for the transmission of Salmonella to human.
      Therefore, there is a need for the establishment of national Salmonella
      surveillance and control programs.

PMID- 27047201
TI  - Rapid detection of Mannheimia haemolytica in lung tissues of sheep and from
      bacterial culture.
AB  - AIM: This study was aimed to detect Mannheimia haemolytica in lung tissues of
      sheep and from a bacterial culture. INTRODUCTION: M. haemolytica is one of the
      most important and well-established etiological agents of pneumonia in sheep and
      other ruminants throughout the world. Accurate diagnosis of M. haemolytica
      primarily relies on bacteriological examination, biochemical characteristics and,
      biotyping and serotyping of the isolates. In an effort to facilitate rapid M.
      haemolytica detection, polymerase chain reaction assay targeting Pasteurella
      haemolytica serotype-1 specific antigens (PHSSA), Rpt2 and 12S ribosomal RNA
      (rRNA) genes were used to detect M. haemolytica directly from lung tissues and
      from bacterial culture. MATERIALS AND METHODS: A total of 12 archived lung
      tissues from sheep that died of pneumonia on an organized farm were used. A
      multiplex polymerase chain reaction (mPCR) based on two-amplicons targeted PHSSA
      and Rpt2 genes of M. haemolytica were used for identification of M. haemolytica
      isolates in culture from the lung samples. All the 12 lung tissue samples were
      tested for the presence M. haemolytica by PHSSA and Rpt2 genes based PCR and its
      confirmation by sequencing of the amplicons. RESULTS: All the 12 lung tissue
      samples tested for the presence of PHSSA and Rpt2 genes of M. haemolytica by mPCR
      were found to be positive. Amplification of 12S rRNA gene fragment as internal
      amplification control was obtained with each mPCR reaction performed from DNA
      extracted directly from lung tissue samples. All the M. haemolytica were also
      positive for mPCR. No amplified DNA bands were observed for negative control
      reactions. All the three nucleotide sequences were deposited in NCBI GenBank
      (Accession No. KJ534629, KJ534630 and KJ534631). Sequencing of the amplified
      products revealed the identity of 99-100%, with published sequence of PHSSA and
      Rpt2 genes of M. haemolytica available in the NCBI database. Sheep specific
      mitochondrial 12S rRNA gene sequence also revealed the identity of 98% with
      published sequences in the NCBI database. CONCLUSION: The present study
      emphasized the PCR as a valuable tool for rapid detection of M. haemolytica in
      clinical samples from animals. In addition, it offers the opportunity to perform
      large-scale epidemiological studies regarding the role of M. haemolytica in
      clinical cases of pneumonia and other disease manifestations in sheep and other
      ruminants, thereby providing the basis for effective preventive strategies.

PMID- 27047202
TI  - Detection and characterization of zoonotic dermatophytes from dogs and cats in
      and around Kolkata.
AB  - AIM: The ringworms of pet dogs, cats, and stray animals (dogs, cats, and other
      animals) could be a potential source of zoonotic infections causing a serious
      public health problem in the busy city Kolkata. The pet owners are more
      susceptible to get this infection from their pets, because of the close contact
      with them as dermatophytosis is very much prevalent in those pets. So, this study
      was aimed to check the prevalence of dermatophytosis in dogs, cats, and in pet
      owners. MATERIALS AND METHODS: A total of 362 clinically suspected cases of
      dermatophytosis from dogs (123 in number), cats (202 in number), and human beings
      (37 in number) were collected and studied from in and around Kolkata to detect
      the presence of significant dermatophytes. Direct microscopy and cultural
      examination of the isolates were performed following standard methodology.
      Identification and characterization of the isolates were done by different
      biochemical tests. RESULTS: Samples (n=285) having significant dermatophytic
      fungal infections were found to be of highest number in cats (158, 55.5%) than in
      dogs (108, 37.8%) and humans (19, 6.7%), respectively. The incidence of
      Microsporum canis (60.0%) was the highest from affecting dogs, cats, and human
      beings in comparison to Microsporum gypseum (22.5%), Trichophyton mentagrophytes
      (15.8%) and Trichophyton rubrum (1.7%). Detection of T. rubrum was only from
      human cases in this study, whereas the presence of rest three were slightly
      higher in cats than that of the dogs and humans in this present study. The
      incidences were higher in young animals and in humans of the age group of 21-30
      years, during the rainy season (from April to August) and also in in-contact
      human beings. CONCLUSION: M. canis was the most commonly pathogen among all
      causing dermatophytosis in animals and also in the pet owners. M. gypseum and T.
      mentagrophytes were other pathogens associated with these infections. These
      infections were more prevalent in the rainy seasons and in in-contact human
      patients or pet owners.

PMID- 27047203
TI  - Incidence and clinical vital parameters in primary ketosis of Murrah buffaloes.
AB  - AIM: The present study was undertaken to ascertain the incidence and clinical
      vital parameters in cases of primary ketosis in Murrah buffaloes brought to
      teaching veterinary clinical complex, Lala Lajpat Rai University of Veterinary
      and Animal Sciences, Hisar and from adjoining villages of the district Hisar,
      Haryana, India. MATERIALS AND METHODS: The investigation was conducted on 24
      clinical cases (out of total 145 screened) of primary ketosis. The diagnosis was
      confirmed on the basis of clinical signs and significantly positive two tests for
      ketone bodies in urine (Rothera's and Keto-Diastix strip test). Data collected
      were statistically analyzed using independent Student's t-test. RESULTS: Overall
      incidence of disease in these areas was found to be 16.55% and all the animals
      were recently parturited (mean: 1.42+/-0.14 month), on an average in their third
      lactation (mean: 2.38+/-0.30) and exhibited clinical signs such as selective
      anorexia (refusal to feed on concentrate diet), drastic reduction in milk yield
      (mean: 64.4+/-5.35%), ketotic odor from urine, breath, and milk and rapid loss of
      body condition. All the clinical vital parameters in ketotic buffaloes (body
      temperature, heart rate, respiration rate, and rumen movements) were within
      normal range. CONCLUSION: Primary ketosis in Murrah buffaloes was the most common
      seen in the third lactation, within the first 2 months after parturition with
      characteristics clinical signs and no variability in vital parameters. The
      disease has severe effect on the production status of affected animal.

PMID- 27047204
TI  - Validation of gamma-radiation and ultraviolet as a new inactivators for foot and
      mouth disease virus in comparison with the traditional methods.
AB  - AIM: The present work deals with different methods for foot and mouth disease
      virus (FMDV) inactivation for serotypes O/pan Asia, A/Iran05, and SAT-2/2012 by
      heat, gamma radiation, and ultraviolet (UV) in comparison with the traditional
      methods and their effects on the antigenicity of viruses for production of
      inactivated vaccines. MATERIALS AND METHODS: FMDV types O/pan Asia, A/Iran05, and
      SAT-2/2012 were propagated in baby hamster kidney 21 (BHK21) and titrated then
      divided into five parts; the first part inactivated with heat, the second part
      inactivated with gamma radiation, the third part inactivated with UV light, the
      fourth part inactivated with binary ethylamine, and the last part inactivated
      with combination of binary ethylamine and formaldehyde (BEI+FA). Evaluate the
      method of inactivation via inoculation in BHK21, inoculation in suckling baby
      mice and complement fixation test then formulate vaccine using different methods
      of inactivation then applying the quality control tests to evaluate each
      formulated vaccine. RESULTS: The effect of heat, gamma radiation, and UV on the
      ability of replication of FMDV "O/pan Asia, A/Iran05, and SAT-2/2012" was
      determined through BHK cell line passage. Each of the 9 virus aliquots titer
      10(8) TCID50 (3 for each strain) were exposed to 37, 57, and 77 degrees C for 15,
      30, and 45 min. Similarly, another 15 aliquots (5 for each strain) contain 1 mm
      depth of the exposed samples in petri-dish was exposed to UV light (252.7 nm
      wavelength: One foot distance) for 15, 30, 45, 60, and 65 min. Different doses of
      gamma radiation (10, 20, 25, 30, 35, 40, 45, 50, 55, and 60 KGy) were applied in
      a dose rate 0.551 Gy/s for each strain and repeated 6 times for each dose. FMDV
      (O/pan Asia, A/Iran05, and SAT-2/2012) were inactivated when exposed to heat >=57
      degrees C for 15 min. The UV inactivation of FMDV (O/pan Asia and SAT-2) was
      obtained within 60 min and 65 min for type A/Iran05. The ideal dose for
      inactivation of FMDV (O/pan Asia, A/Iran05, and SAT-2/2012) with gamma radiation
      were 55-60 and 45 kGy, respectively. Inactivation of FMDV with binary was 20, 24
      and 16 hr for O/pan Asia, A/Iran05, and SAT-2/2012, respectively while
      inactivation by (BEI+FA) was determined after 18, 19 and 11 hr for O/pan-Asia,
      A/Iran 05, and SAT-2/2012, respectively. The antigenicity of control virus before
      inactivation was 1/32, it was not changed after inactivation in case of gamma
      radiation and (BEI+FA) and slightly decrease to 1/16 in case of binary and
      declined to 1/2, 1/4 in case of heat and UV inactivation, respectively. The
      immune response induced by inactivated FMD vaccines by gamma radiation and
      (BEI+FA) lasted to 9 months post-vaccination, while the binary only still up to 8
      months post-vaccination but heat and UV-inactivated vaccines were not effective.
      CONCLUSION: Gamma radiation could be considered a good new inactivator inducing
      the same results of inactivated vaccine by binary with formaldehyde (BEI+FA).

PMID- 27047205
TI  - Emergence of oriental theileriosis in cattle and its transmission through
      Rhipicephalus (Boophilus) microplus in Assam, India.
AB  - AIM: The aim of the present study was to investigate the presence of Theileria in
      blood samples of crossbred and indigenous adult cows raised under unorganized
      small scale farming system in a Babesia and Anaplasma endemic geographical area
      from Assam, India and to see its transmission through Rhipicephalus (Boophilus)
      microplus ticks. MATERIALS AND METHODS: For the present study, 57 clinical cases
      of cattle suspected to be of hemoparasitic infections were taken into
      consideration. The parasites were identified based on morphology in giemsa
      stained blood smear followed by polymerase chain reaction (PCR). Sera samples
      were tested for T. annulata antibodies in plate and Dot-ELISA. PCR was also
      conducted in eggs of Rhipicephalus (Boophilus) microplus tick collected from a
      Theileria orientalis positive animal. RESULTS: PCR amplified 1124, 776, and 160
      bp DNA fragments of B. bigemina (64.91%), T. orientalis (21.05%) and A. marginale
      (14.03%), respectively. This assay further conducted in 12 T. orientalis positive
      blood samples with primers of Buffeli, Chitose, and Ikeda variants of T.
      orientalis showed 3 samples positive to Ikeda type and none for Buffeli and
      Chitose. Babesia bovis and Theileria annulata specific primers also did not
      amplify any fragment during the PCR assay of the blood samples. Further, all sera
      samples tested negative to T. annulata antibodies in Plate and Dot-ELISA. PCR
      conducted in eggs of R (B).microplus tick collected from a T. orientalis positive
      animal revealed presence of the parasite DNA. Gradual improvement in physical
      condition leading to complete recovery in 10 out of 12 T. orientalis infected
      clinical cases treated with buparvaquone(at 2.5mg/kg.b.wt I/M) was the feedback
      obtained from field veterinarians and the cattle owners. CONCLUSION: The present
      investigation represents the first report of occurrence of T. orientalis in
      cattle of Assam with involvement of pathogenic Ikeda strain in clinical outbreaks
      and its possible natural transmission by R (B). microplus through the
      transovarian mode.

PMID- 27047206
TI  - Assessment of blood changes post-challenge with Corynebacterium
      pseudotuberculosis and its exotoxin (phospholipase D): A comprehensive study in
      goat.
AB  - AIM: There is very little information regarding blood changes during the
      challenge of phospholipase D (PLD) in goats. Therefore, this experiment was
      conducted to study the changes in blood after the challenge with Corynebacterium
      pseudotuberculosis and its exotoxin, PLD to fill in the gap of caseous
      lymphadenitis (CLA) research. MATERIALS AND METHODS: Twenty-six crossbred Boer
      goats aged 12-14 months were divided into 3 groups; the first group n=6 was
      inoculated with 1 ml phosphate buffered solution s.c. as the control. The second
      group n=10 was inoculated with C. pseudotuberculosis 1 * 10(9) cfu s.c. The third
      group n=10 was intravenous injected with PLD 1 ml/20 kg body weight. Serial blood
      collections were done at 1 h, 3 h, 5 h, 8 h, and 12 h then every 24 h post
      inoculation for the first 30 days of the experiment. Subsequently, the blood
      collection continued twice a week till the end of the experiment (90 days post
      challenge). RESULTS: Both C. pseudotuberculosis and PLD treated groups showed
      significant changes (p<0.05) in red blood cell count, hemoglobin (Hb), packed
      cell volume, mean corpuscular volume, mean corpuscular Hb concentration, white
      blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, basophils,
      globulin, and total plasma proteins. Similarly, both treated groups showed
      significant changes (p<0.05) in alanine transaminase, alkaline phosphatase,
      aspartate transaminase, total bilirubin, calcium concentration, creatine
      phosphokinase, creatinine, gamma-glutamyl transpeptidase, urea concentration,
      lactate dehydrogenase, prothrombin time, and activated partial thromboplastin
      time. CONCLUSION: It concluded that C. pseudotuberculosis and PLD have a negative
      impact on the goat's health in general reflected by all those changes recorded in
      the hemogram, leukogram, and the blood chemistry.

PMID- 27047207
TI  - Prevalence of Cryptosporidia, Eimeria, Giardia, and Strongyloides in pre-weaned
      calves on smallholder dairy farms in Mukurwe-ini district, Kenya.
AB  - AIM: Gastrointestinal diseases are among the leading causes of calf morbidity and
      mortality in Kenya and elsewhere. This study was undertaken to determine the
      prevalence of Cryptosporidia, Eimeria, Giardia, and Strongyloides in calves on
      smallholder dairy farms (SDF) in Mukurwe-ini District, Nyeri County, Kenya. These
      infections have been associated with economic losses by decreased growth rates,
      decreased productivity, and increased susceptibility to other diseases. MATERIALS
      AND METHODS: An observational study was conducted on 109 farms in Mukurwe-ini
      District, Nyeri County, Kenya, where 220 calf fecal samples (each calf at 4 and 6
      weeks of age) from 110 calves (1 set of twins) were collected and analyzed for
      Cryptosporidia, Eimeria, Giardia, and helminth parasites. RESULTS: Eimeria
      oocysts, Cryptosporidia oocysts, and Strongyloides eggs were detected in the
      fecal samples examined, but no Giardia cysts were found. The overall period
      prevalence of Eimeria, Cryptosporidia, and Strongyloides was 42.7% (47/110),
      13.6% (15/110), and 5.4% (6/110), respectively. The prevalence at 4 weeks of age
      for Eimeria, Cryptosporidia, and Strongyloides was 30.0% (33/110), 8.2% (9/110),
      and 3.7% (4/109), respectively, while the prevalence at 6 weeks of age was 20.2%
      (22/109), 6.5% (7/107), and 2.7% (3/110), respectively. There was, however, no
      significant difference in the prevalence at 4 and 6 weeks (p>0.05). CONCLUSION:
      Findings from this study show that Eimeria, Cryptosporidia, and Strongyloides,
      are prevalent in the study area and indicate the need to adopt optimal management
      practices to control infections in calves.

PMID- 27047208
TI  - Effect of partial supplementation of sun-dried Azolla as a protein source on the
      immunity and antioxidant status of commercial broilers.
AB  - AIM: The present study was conducted to evaluate the effect of partial
      supplementation of sun-dried Azolla as a protein source on the immunity of
      commercial broilers in coastal Odisha. MATERIALS AND METHODS: A 180 day-old
      broiler chicks were distributed in six dietary treatments viz. C1: Basal diet,
      C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet +
      5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4:
      Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc
      hypersensitivity (CBH) and humoral immunity response were determined at the
      38(th) day of age. At 42(nd) day, the weight of lymphoid organs, an antioxidant
      enzyme, and lipid peroxidation activity were determined. RESULTS: The CBH
      response did not differ significantly among the treated groups, but the sheep red
      blood cells response was significantly higher in T4. The weight of lymphoid
      organs or immune organs of all the treated groups did not differ significantly
      (p>0.05). The erythrocyte catalase level of T4 group was found to be
      significantly higher than rest of the treated groups except T3. CONCLUSION: It
      may be concluded that supplementation of Azolla at 10% of dietary protein
      requirement along with enzyme supplementation in an isonitrogenous diet showed a
      better immune response in broilers.

PMID- 27047209
TI  - Immunological, hematological, biochemical, and histopathological studies on cows
      naturally infected with lumpy skin disease.
AB  - AIM: Lumpy skin disease (LSD) is an infectious viral disease of cattle caused by
      LSD virus (LSDV) of the family Poxviridae characterized by skin nodules covering
      all parts of the body. There are many aspects of LSD remaining unknown, thus
      immunological, hematological, and biochemical parameters were estimated.
      MATERIALS AND METHODS: During an outbreak of LSD in Sharkia governorate from
      Egypt, 211 cows aging (2-4 years) were examined clinically for the presence of
      LSD lesions during the period from July to November 2014. A total of 134 cows
      from those showed lesions suspected to be LSD. RESULTS: Recorded clinical signs
      were pyrexia with the development of skin nodules of varying sizes which ranged
      from a few to several hundred sometimes coalesced together. Enlargements of the
      peripheral lymph nodes. Intracytoplasmic inclusion bodies were noticed in the
      histopathological examination. Immunological studies revealed a significant
      decrease of lymphocyte transformation rate, phagocytic % and killing % which was
      marked within 2 weeks postinfection. LSD resulted in non-significant in hemogram
      in 1(st)-2(nd) day post-infection while a macrocytic hypochromic anemia within 10
      14(th) days post-infection. Leucopenia and lymphopenia were recorded 1(st)-2(nd)
      day post-infection while at 10-14(th) showed granulocytic leucocytosis.
      Biochemical analysis revealed hypoproteinemia, hypoalbuminemia, and
      hyperglobulinemia especially gamma globulins. There were a significant increase
      in serum alanine aminotransferase, aspartate aminotransferase activities,
      creatinine level, blood urea nitrogen and creatine phosphokinase. CONCLUSION:
      LSDV infected cows in early stages revealed leucopenia. Immunosuppressive effect
      was pronounced later. In late stage revealed hemolytic anemia, leucocytosis and
      increase of serum CK, which could aid in diagnosis. Disturbance in liver and
      kidney function tests have been occurred.

PMID- 27047210
TI  - Effect of temperature variation on hormonal concentration at various gestation
      stages in black Bengal goat.
AB  - AIM: The present study was conducted to evaluate the effect of risingtemperature
      on the metabolic as well as the reproductive performance of the black Bengal
      goat. MATERIALS AND METHODS: A total 27 numbers of non-pregnant black Bengal
      goats of the same parity comprised the experimental animals. The selected goats
      were randomly assigned to 3 groups of 9 each, maintaining uniformity in body
      weight (average 14-18 kg). Goats in Group-I were kept between the temperature
      ranges of 35-40 degrees C, in Group-II between 20 degrees Cand 27 degrees C, and
      Group-III were kept under loose housing system and serve as a control. Goats in
      all the groups were bred naturally. Blood was collected prior to feeding in the
      morning on the day 1 (estrus), 20, 45, 90, and 135, expected day of parturition
      and also 2 days after parturition from goats of all the three groups. RESULTS: It
      was observed that the level of plasma estrogen decreased (p<0.05) up to day 45 of
      gestation, then after increased up to 135 days of gestation and was maximum on
      expected day of parturition which was significantly (p<0.05) higher than all the
      values. Plasma progesterone level increased from day 20 and was the highest on
      day 90 and then decreased significantly (p<0.05) on expected date of parturition.
      The luteinizing hormone value decreased significantly (p<0.05) on expected day of
      parturition and day 2 after parturition in all the groups. Follicle stimulating
      hormone concentration showed a significant (p<0.05) decrease from day 1 to 2 days
      after parturition in all the groups. The plasma triiodothyronine (T3) level did
      not vary between and within the treatment groups at any stage of the experiment.
      The plasma thyroxine (T4) level varied significantly (p<0.01) within and (p<0.05)
      between groups at all stages of reproduction. A significant (p<0.05) variation in
      plasma cortisol concentration in all the groups increased significantly until the
      day of parturition and dropped significantly (p<0.01) in 2 days after parturition
      in all the groups. CONCLUSION: The present experiment revealed that rise in
      temperature has no any deleterious effect on the metabolic as well as the
      reproductive hormonal concentrationat variousstages of gestation inblack Bengal
      goat.

PMID- 27047211
TI  - Epidemiological surveillance of capybaras and ticks on warning area for Brazilian
      spotted fever.
AB  - AIM: The vulnerability of tropical developing countries to the emerging disease
      constitutes a critical phenomenon in which the invasion of wild niches by human
      hosts, contributes to expansion of zoonotic diseases, such as the Brazilian
      spotted fever (BSF). This study performed a diagnosis of species occurrence of
      their hosts (Hydrochoerus hydrochaeris) and vectors (Amblyomma sculptum and
      Amblyomma dubitatum) on the warning area for this reemerging disease in Brazil.
      MATERIALS AND METHODS: The study was conducted in a warning area for BSF in the
      city of Americana, Sao Paulo state. The occurrence of capybaras was registered by
      use of binoculars and GPS equipment and 24 acarological researches were performed
      through 180 CO2 traps. Samples of adult ticks were dissected for salivary glands
      removal, DNA extraction, and evaluation by polymerase chain reaction (PCR) being
      tested by initial gltA-PCR, ompA-PCR, and Rickettsia bellii-specific PCR, with
      the positive samples subjected to sequencing. RESULTS: Eleven clusters of
      capybaras (total of 71 individuals), were observed along the riparian of Ribeirao
      Quilombo and 7,114 specimens of A. sculptum and 7,198 specimens of A. dubitatum
      were collected in this same area. About 568 samples of adult ticks were dissected
      for salivary glands removal, DNA extraction and evaluation by gltA-PCR, with
      results of 1.94% (11/568) of positive samples. Results for the initial gltA-PCR
      indicated none positive sample to Rickettsia species into A. sculptum and 11
      positive samples to A. dubitatum. These samples were negative to the ompA-PCR and
      positive to the Rickettsia bellii-specific PCR protocol and subjected to DNA
      sequencing, whose result indicated 100% similarity to Rickettsia bellii. The
      distribution of tick species A. sculptum and A. dubitatum was configured
      regarding to the biotic potential of the riparian areas, measuring the risks for
      BSF in peri-urban areas of Americana. CONCLUSION: These results confirmed a
      status of epidemiological warning with a strong association of the amplifiers
      hosts of Rickettsia and tick vectors for the transmission of BSF to humans in
      this region.

PMID- 27047212
TI  - Effect of selenium supplementation on performance, cost economics, and
      biochemical profile of Nellore ram lambs.
AB  - AIM: Present experiment was conducted to investigate the effect of selenium (Se)
      supplementation on performance, carcass characteristics, meat composition,
      shelflife of meat and biochemical profile in Nellore ram lambs. MATERIALS AND
      METHODS: 24 male Nellore ram lambs (15.75+/-0.47 kg) were randomly divided into
      four dietary groups with six lambs in each and reared under uniform management
      conditions for 120 days. Basal diet was not supplemented with Se and consisted of
      green fodder (Se 0.09 mg/kg dry matter [DM]), dry roughage (Se 0.11 mg/kg DM) and
      concentrate mixture (Se 0.019 mg/kg DM) and fed individually. Dietary treatments
      were prepared by adding graded levels Se (0, 0.45, 0.9, and 1.8 ppm) to
      concentrate mixture (1% body weight [BW]) from sodium selenite. Feed offered and
      refusal measured daily; and BWs were measured at fortnight interval to find out
      average daily gain (g), feed conversion ratio (FCR), cost economics and plane of
      nutrition. Serum biochemical profile (concentration of glucose, total protein,
      albumin, globulin, cholesterol, and hemoglobin) was assessed on 0, 60(th), and
      120(th) day. At the end of experiment, the carcass characteristics (dressing
      percentage, cut-up parts, meat to bone ratio) and meat chemical composition were
      evaluated. Meat keeping (thiobarbituric acid reactive substances) quality from
      different groups was evaluated on day 0, 3, and 6 post-slaughter. RESULTS:
      Dietary Se supplementation did not show any effect on weight gain, FCR, cost
      economics, plane of nutrition, and serum biochemical profile in Nellore ram
      lambs. However, Se supplemented lambs had numerically higher weight gain than the
      unsupplemented lambs. Similarly, carcass characteristics and keeping quality were
      comparable among the four treatments. However, numerical increase in post
      slaughter keeping quality with increasing Se supplementation was observed.
      CONCLUSION: It can be concluded that supplementation of Se in the form of sodium
      selenite (inorganic source) at different levels did not influence animal
      performance in growing Nellore ram lambs had no effect on lamb performance, cost
      economics, carcass characteristics, and serum biochemical profile.

PMID- 27047213
TI  - Replacement of inorganic zinc with lower levels of organic zinc (zinc nicotinate)
      on performance, hematological and serum biochemical constituents, antioxidants
      status, and immune responses in rats.
AB  - AIM: A study was undertaken to investigate the effect of organic zinc (zinc
      nicotinate, Zn-nic) supplementation (6, 9, and 12 ppm) compared to inorganic zinc
      (12 ppm) on growth performance, hematology, serum biochemical constituents
      oxidative stress, and immunity in weaned female Sprague-Dawley rats. MATERIAL AND
      METHODS: A 48 weaned rats (285.20+/-1.95 g) were randomly distributed to 4
      dietary treatments with 6 replicates in each and reared in polypropylene cages
      for 10 weeks. Basal diet (BD) was formulated with purified ingredients without
      zinc (Zn). Four dietary treatments were prepared by adding 12 ppm Zn from ZnCO3
      (control) and 6, 9, and 12 ppm Zn from Zn-nic to the BD. On 42(nd) day, blood was
      collected by retro-orbital puncture for analyzing hematological constituents,
      glucose, cholesterol, alkaline phosphatase, total protein, albumin, and globulin
      and antioxidant enzyme activities. At 43(rd) day, rats were antigenically
      challenged with sheep red blood cell (RBC) to assess humoral immune response and
      on 70(th) day cell-mediated immune response. RESULTS: Weekly body weight gains,
      daily feed intake, blood hematological constituents (white blood cell, RBC,
      hemoglobin concentration, packed cell volume, mean corpuscular volume,
      lymphocyte, monocyte, and granulocyte concentration) and serum glucose, total
      protein levels were comparable among the rats feed Zn from ZnCO3 and Zn-nic (6,
      9, and 12 ppm). Serum cholesterol reduced with organic Zn supplementation at
      either concentration (6-12 ppm). Serum globulin concentration reduced (p<0.05)
      with 6 ppm Zn-nic supplementation compared to other dietary treatments. Lipid
      peroxidation lowered (p<0.05) reduced with 12 ppm organic Zn; thiobarbituric acid
      reacting substances and protein carbonyls concentrations in liver reduced
      (p<0.05) with 9 and 12 ppm levels of organic Zn supplementation compared to 12
      ppm Zn supplementation from inorganic source. RBC catalase and glutathione
      peroxidase enzymes activities were highest (p<0.05) in rats supplemented with 12
      ppm Zn-nic, followed by 9 ppm. Comparable immune response (humoral and cell
      mediated) was observed between 12 ppm inorganic Zn and 9 ppm organic Zn and
      higher (p<0.05) immune response was noticed at 12 ppm Zn-nic supplementation.
      CONCLUSION: Based on the results, it is concluded that dietary Zn concentration
      can be reduced by 50% (6 ppm) as Zn nicotinate without affecting growth
      performance, hemato-biochemical constituents, antioxidant status, and immunity.
      In addition, replacement of 12 ppm inorganic Zn with 12 ppm organic Zn
      significantly improved antioxidant status and immune response.

PMID- 27047214
TI  - The influence of VKORC1 and CYP2C9 mutations on warfarin response after total hip
      and knee arthroplasty.
AB  - AIMS: This study characterizes the influence of genotype at two loci on warfarin
      response after arthroplasty. METHODS: 121 postarthroplasty patients given
      warfarin thromboprophylaxis were reviewed for international normalized ratio
      (INR) values on the first three days postoperatively. Significant differences
      among genotypes in INR values on each of the first three postoperative days were
      assessed. RESULTS: Wild-type patients at both loci (~23% of patients) had yet to
      reach therapeutic INR (1.5-2.0) by postoperative day three more frequently than
      those with a mutation conferring hyper-responsiveness (61% vs. 30%; P <= .01).
      CONCLUSIONS: Wild-type patients are not anticoagulated in a sufficiently prompt
      manner after arthroplasty.

PMID- 27047215
TI  - Radiological and histopathological examination of apparent lytic lesions in
      allograft long bones-No cause for concern.
AB  - OBJECTIVE: Identify the nature of apparent lytic lesions within human allograft
      specimens from patients with no known malignancy, using radiological and
      histopathological analysis. METHODS: 123 Post-retrieval radiographs from 23
      donors were examined. Sixty-seven radiographs were noted to show apparent lytic
      lesions. The number, size, character and position of the apparent lesions were
      recorded. RESULTS: CT scanning of 9 specimens confirmed the lesions to be of air
      pockets causing artefact. Histopathological analysis showed no malignant or
      pathological process. CONCLUSIONS: Apparent lesions were not pathological.
      PRACTICE IMPLICATIONS: Specimens with similar appearances, in donors with no
      malignancy, can be safely used in donation.

PMID- 27047216
TI  - High rates of postoperative urinary retention following primary total hip
      replacement performed under combined general and spinal anaesthesia with
      intrathecal opiate.
AB  - BACKGROUND: Postoperative urinary retention (POUR) occurs frequently following
      hip replacement. METHODS: 94 consecutive primary hip arthroplasty patients were
      assessed prospectively for POUR. 80 patients followed our anaesthesia protocol
      with combined general and spinal anaesthesia using bupivacaine and intrathecal
      diamorphine. RESULTS: 29 instances of POUR with higher rates in men and younger
      patients (under-50s), independent of either pre-existing renal impairment or
      opiate strength. POUR was observed to increase length of stay by 1.6 days.
      CONCLUSIONS: We report a 36% overall rate of POUR. Males demonstrated a 3-fold
      increased risk. Patients should be counselled pre-operatively on the risk of
      urinary retention.

PMID- 27047217
TI  - Patient functional outcomes with trapeziectomy alone versus trapeziectomy with
      TightRope((r)).
AB  - PURPOSE OF THE STUDY: We assess whether patient functional outcomes with the use
      of a tightrope in conjunction with trapeziectomy are better than traditional
      trapeziectomy alone. METHODS: Retrospective study of 56 trapeziectomies in 53
      patients; 26 trapeziectomies alone without additional procedures, and 30
      trapeziectomies performed in conjunction with tightrope suspensionplasty. All
      patients were scored using Quick DASH, Patient-Rated Wrist Evaluation and Nelson
      base of thumb arthritis scores pre- and post-operatively. RESULTS: Significant
      improvements were seen with both operations using all three scoring systems.
      However, there was no statistically significant difference in post-operative
      scores between the two operations. STUDY DESIGN: Retrospective comparative study.
      LEVEL OF EVIDENCE: III.

PMID- 27047218
TI  - The effect of platelet-rich plasma injection on lateral epicondylitis following
      failed conservative management.
AB  - OBJECTIVE: We assessed the effect PRP injection on pain and function in patients
      with lateral epicondylitis where conservative management had failed. METHODS: We
      prospectively reviewed 34 patients. The mean follow-up was 26 weeks (range 6-114
      weeks). We used the Oxford Elbow Score (OES) and progression to surgery to assess
      outcomes. RESULTS: 88.2% improved their OES. 8.8% reported symptom progression.
      One patient had no change. No patients suffered adverse reactions. Two patients
      underwent an open release procedure. One had the injection repeated. CONCLUSION:
      An injection of PRP improves pain and function in patients suffering from LE
      where conservative management has failed.

PMID- 27047219
TI  - Comparison of single event vs multiple event soft tissue surgeries in the lower
      extremities with cerebral palsy.
AB  - In children with spasticity of multiple muscle groups, the need for repeat
      surgical interventions increases with advancing age. AIM: The present study aimed
      to investigate retrospectively whether there are any clinical and functional
      differences between single-event multilevel surgeries and multiple surgical
      events at a single level. METHOD: The medical records of 109 patients with
      cerebral palsy (CP) were used. The patients, who met the inclusion and exclusion
      criteria, were assigned into following 4 groups based on the surgical procedures.
      The Gross Motor Function measure-88 (GMFCS) and Functional Independence Measure
      for Children (WeeFIM) were used for assessments. RESULTS: When compared to
      groups, there was no significant difference. This study showed that both surgical
      techniques resulted in improvements in GMFCS and WeeFIM levels.

PMID- 27047220
TI  - Endoscopic plantar fasciotomy versus injection of platelet-rich plasma for
      resistant plantar fasciopathy.
AB  - BACKGROUND: Resistant plantar fasciopathy is a common orthopedic problem. AIM:
      Comparing two different methods of treatment. METHODS: Fifty patients with
      chronic resistant plantar fasciopathy were divided into two groups. The first
      included 23 patients treated by endoscopic release of plantar fascia (EPF) and
      the second included 27 patients treated by injection of platelet-rich plasma
      (PRP). RESULTS: In the EPF group, the average VAS improved from 8.28 to 2.35. The
      average AOFAS improved from 65 to 94. In the PRP group, average VAS improved from
      8.22 to 2.9 and the average AOFAS improved from 66 to 92. CONCLUSION: Both
      methods gave comparable results at late follow-up.

PMID- 27047221
TI  - Mechanobiology in the management of mobile atrophic and oligotrophic tibial
      nonunions.
AB  - BACKGROUND: Recent research indicates that atrophic nonunions are biologically
      active and may heal in the optimal biomechanical environment. METHODS: Thirty
      three patients with mobile atrophic and oligotrophic tibial nonunions were
      treated with circular external fixation and functional rehabilitation. Seven
      patients required autogenous bone graft procedures. RESULTS: Bony union was
      achieved after the initial surgery in 31/33 (93.9%) tibias. Two persistent
      nonunions were successfully treated with repeat circular external fixation
      without bone graft. This resulted in final bony union in 33/33 (100%) patients.
      CONCLUSION: Mechanobiological stimulation of tibial nonunions can produce union
      even if the biological activity appears to be low.

PMID- 27047222
TI  - Improving the accuracy of wide resection of bone tumors and enhancing implant
      fit: A cadaveric study.
AB  - BACKGROUND/AIMS: Customized three-dimensional (3-D) jigs have been shown to
      increase the accuracy of skeletal tumor resection in comparison to freehand
      techniques. However, the utility of these jigs in subsequently enhancing the fit
      of endoprosthetic implants has yet to be determined. We hypothesized that custom
      jigs would improve implant fit compared to freehand resection. METHODS: Nine
      matched pairs of cadaveric femurs were scanned by CT. The images then had
      'virtual' tumors positioned on the distal medial femoral condyle and preoperative
      resection plans were generated. Custom implants were designed to fit into the
      resected spaces and 3-D printed. Similarly, customized 3-D jigs were designed and
      printed for half of the femurs. Resections were then performed using the jigs or
      freehand. The implants were positioned in the resected femurs and the accuracy-of
      fit was quantitatively assessed by re-scanning the resected femurs and
      calculating the deviation from the implant (in degrees) for each of the 3 cutting
      planes. The results were then compared between jig and freehand resections.
      RESULTS: For the first plane, the jig resulted in less deviation than the
      freehand cut, but it did not achieve statistical significance. However, for the
      2nd and 3rd planes, the jigs deviated 1.78 degrees  and 2.20 degrees  from the
      implants compared to 4.41 degrees  and 7.96 degrees  for the freehand cuts, both
      of which were statistically significant improvements (p = 0.038 and p = 0.003).
      CONCLUSION: In summary, customized 3-D jigs were shown to improve the accuracy-of
      fit between implants and host bone, moving this technology closer to clinical
      implementation.

PMID- 27047223
TI  - Perioperative adverse events in distal femur fractures treated with
      intramedullary nail versus plate and screw fixation.
AB  - BACKGROUND: To compare 30-day outcomes in patients treated for a distal femur
      (DF) fracture with plate fixation (PF) or intramedullary nail (IMN). METHODS:
      Differences in rates of any adverse events (AAE), serious adverse events (SAE),
      infectious complications, and mortality were explored between groups in the ACS
      NSQIP database. RESULTS: There were 511 PF and 44 IMN patients. The PF group and
      IMN groups had similar rates of AAEs (p = 0.35), SAEs (p = 0.46), infectious
      complications (p = 1.00), and mortality (p = 0.39). CONCLUSIONS: DF fractures
      treated with IMN have equivalent short-term outcomes compared to those treated
      with PF.

PMID- 27047224
TI  - Articular cartilage and local anaesthetic: A systematic review of the current
      literature.
AB  - BACKGROUND: Chondrolysis involves the breakdown of cartilage following
      arthroscopic surgery, most commonly affecting the glenohumeral joint. METHODS:
      This review summarises all clinical and laboratory studies regarding local
      anaesthetic (LA) and its association with chondrolysis. We identified 289 papers,
      41 of which met our inclusion criteria and were included in the final review.
      RESULTS: Bupivacaine, lidocaine, ropivacaine and levobupivacaine are all toxic to
      cartilage. Intra-articular infusions confer a greater toxicity to cartilage than
      single injections. CONCLUSIONS: Intra-articular LA pain pumps carry a high risk
      of chondrolysis and should be avoided. Further studies are indicated to assess
      long-term single exposure LA implications.

PMID- 27047225
TI  - The Headless Compression Screw - Technical challenges in scaphoid fracture
      fixation.
AB  - BACKGROUND: The Headless Compression Screw((r)) (HCS) is a cannulated screw that
      is used for scaphoid fracture fixation. The screw generates compression across
      the fracture site prior to being countersunk below the articular surface.
      METHODS: We performed a retrospective review of 56 consecutive scaphoid fixations
      using this device in patients with both acute and chronic fractures. RESULTS:
      Union rates were 100% in acute and 87% in chronic fractures. 16% of patients
      required screw removal for protrusion. CONCLUSION: Despite placement of the screw
      in line with technical guidance, protrusion was significant and can be a source
      of ongoing morbidity.

PMID- 27047226
TI  - Trends in vertebroplasty and kyphoplasty after thoracolumbar osteoporotic
      fracture: A large database study from 2005 to 2012.
AB  - PURPOSE: The aim of our study was to investigate the trends and incidence of
      vertebral augmentation procedures (VAPs) in treating osteoporotic vertebral
      compression fractures. RESULTS: In total, 118,074 patients were analyzed. The
      overall incidence of VAPs was 15.2%. The incidence of VAPs was significantly
      higher in those 75-79 years old (20.4%), significantly higher in females than
      males (15.6% versus 14.9%), and most commonly performed in the South (17.7%).
      CONCLUSION: There was a decline in the frequency of these procedures since 2008,
      but physicians are still performing these procedures, albeit at a much lower
      frequency than before 2009.

PMID- 27047227
TI  - NELL-1 expression in tumors of cartilage.
AB  - BACKGROUND/AIMS: NELL-1 is a novel osteochondral differentiation factor protein
      with increasing usage in tissue engineering. Previously, we reported the
      expression patterns of NELL-1 in bone-forming skeletal tumors. With increasing
      interest in the use of NELL-1 protein, we sought to examine the expression of
      NELL-1 in cartilage-forming tumors. METHODS: Immunohistochemical expression was
      examined in human pathologic specimens. RESULTS: Consistent NELL-1 overexpression
      across all cartilage-forming tumors was observed. Similar degrees of expression
      were observed in enchondroma, chondrosarcoma, and chondroblastic osteosarcoma.
      NELL-1 expression did not significantly vary by tumor grade. CONCLUSION: In
      summary, NELL-1 demonstrates reliable and consistent expression across cartilage
      forming skeletal tumors.

PMID- 27047228
TI  - The effects of orthosis on thoracolumbar fracture healing: A review of the
      literature.
AB  - BACKGROUND: Various methods have been used as a conservative treatment of stable
      thoracolumbar fracture. Presently, it is controversial, whether the use of spinal
      orthoses reduces pain and deformity associated with vertebral fracture or not.
      Therefore, the aim of this study was to determine the effects of orthoses on
      vertebral fractures healing in thoracolumbar area. MATERIALS AND METHODS: A
      search was carried out on Medline, ISI web of knowledge, Google Scholar and
      Embasco. The keywords used included thoracolumbar fracture; brace, orthosis, and
      conservative treatment. RESULTS: Twenty-one papers were selected for final
      analysis. The quality of the most of the papers was poor, as most of them were
      retrospective studies with various follow-up periods. DISCUSSION: Based on the
      results of these studies, it can be concluded that subjects with a fracture of
      thoracolumbar achieved a high ability to return to their jobs. The use of
      orthosis did not influence the kyphosis angulation in subjects with stable
      fracture in thoracolumbar spine. The effects of orthoses would be mostly
      immobilization, protection and remaining.

PMID- 27047229
TI  - Clinical evaluation and surgical options in acetabular reconstruction: A
      literature review.
AB  - The purpose of this paper is to review the clinical indications for acetabular
      reconstruction in patients with underlying peri-prosthetic segmental and cavitary
      defects, evaluate steps in pre-operative planning, and present the American
      Academy of Orthopaedic Surgeons (AAOS) and Paprosky classification systems to
      categorize acetabular defects. We also present a review of the current surgical
      techniques to reconstruct the acetabular socket which includes a cementless
      acetabular component with morselized bone, structural allograft, jumbo and oblong
      cups, reinforcement rings, bone cages, custom triflange acetabular constructs,
      and trabecular metal components. 

PMID- 27047230
TI  - Arthroscopic grading of common wrist disorders and its role in management.
AB  - Palmer devised a classification system to guide treatment of triangular
      fibrocartilage complex tears in 1989. The main division is between traumatic Type
      I and atraumatic Type II tears. The wrist arthroscopy makes diagnosis and
      treatment of ulnar impaction syndrome possible in a less invasive way.
      Arthroscopy is the most valuable tool for diagnosis and treatment of acute
      scapholunate and lunotriquetral dissociation. Arthroscopic grading of Kienbock's
      disease better describes articular damage compared with plain radiographs and can
      help surgical treatment. The wrist arthroscopy generally makes it possible to
      make the diagnosis of the chondral lesion before they are visible by the usual
      imaging. 

PMID- 27047231
TI  - An unusual karyotype in leiomyoma: Case report and literature review.
AB  - Vascular leiomyoma are uncommon, clinically benign smooth muscle tumors. Here we
      report a case of an otherwise typical leiomyoma with unusual cytogenetic changes
      including t(1;10). Reports from the existing literature suggest that
      approximately 40-50% of leiomyomas contain nonrandom chromosomal abnormalities of
      which a subset is tumor specific. t(12;14)(q15;q24) is one of the most common
      translocations, which occur in approximately 20% of karyotypes. Additional
      aberrations include del(7)(q22-q32), trisomy 12, and 6p21 rearrangements. Other
      recurrent abnormalities include monosomy 22, monosomy 10, del(10q), and
      structural rearrangements of chromosome 3. 

PMID- 27047232
TI  - Reconstruction with non-vascularized fibular autograft after resection of
      clavicular benign tumor.
AB  - Chondroblastoma is a rare, benign cartilaginous neoplasm that accounts for
      approximately 1% of all bone tumors, and approximately 4% of all chondroblastomas
      arise in the clavicle. Here, we report a case of chondroblastoma in the right
      clavicle. 27-year-old female patient presented with a 12-month history of
      shoulder pain. Based on radiological and pathological examination, the diagnosis
      was compatible with chondroblastoma. After resection of the tumor, 1 cm of the
      distal clavicle was preserved, 15 cm of the non-vascularized fibula was taken
      from the contralateral leg and placed on the site of the clavicle and fixed with
      hook plate at distal clavicle and reconstruction plate attached to the sternum.
      13 months of follow-up is scheduled for removal of osteosynthesis material,
      finding full consolidation of sternoclavicular segment and the distal segment. A
      good functional outcome was apparent after a limited 14-month follow-up, and the
      patient was highly satisfied with the result. We found no recurrence or
      metastasis. 

PMID- 27047233
TI  - Brown-Sequard syndrome produced by calcified herniated cervical disc and
      posterior vertebral osteophyte: Case report.
AB  - Brown-Sequard syndrome (BSS) produced by cervical disc disorders has rarely been
      seen clinically and only 50 cases have been reported in English literatures.
      However, most of which have resulted from acute disc herniation. Here, we report
      a case of BSS produced by calcified herniated C4-C5 disc and posterior vertebral
      osteophyte, in which decompression through anterior approach was performed. This
      case revealed the potential of cervical spondylopathy leading to BSS in a chronic
      manner. Once the diagnosis is established, it is advisable to perform
      decompression as early as possible. 

PMID- 27047235
TI  - The alien ascidian Styela clava now invading the Sea of Marmara (Tunicata:
      Ascidiacea).
AB  - During the implementation of a large project aimed to investigate the benthic
      community structures of the Sea of Marmara, specimens of the invasive ascidian
      species Styela clava were collected on natural substrata (rocks) at 10 m depth at
      one locality (Karamursel) in Izmit Bay. The specimens were mature, containing
      gametes, indicating that the species had become established in the area. The Sea
      of Marmara seems to provide suitable conditions for this species to survive and
      form proliferating populations. 

PMID- 27047234
TI  - Defining Essential Features of Myalgic Encephalomyelitis and Chronic Fatigue
      Syndrome.
AB  - Considerable debate surrounds the search for the defining features of patients
      with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Current
      case definitions were created through clinical consensus. Failure to
      operationalize these case definitions has led to considerable variability in the
      identification of patients. In addition, some case definitions (e.g., Fukuda et
      al., 1994) do not require cardinal symptoms of this illness, where as other case
      definitions do require core symptoms of this illness (Carruthers et al., 2003,
      2011), and these latter case criteria appear to identify a more impaired group of
      patients. Criterion variance is most likely to occur when operationally explicit
      criteria do not exist for diagnostic categories (Spitzer, Endicott, & Robins,
      1978), or when there are varying criteria for contrasting case definitions, which
      is an impediment to the research in this field. To deal with this problem, it is
      possible to differentiate those that meet more loosely defined criteria from
      those that are more narrowly and defined, thus differentiating CFS from ME. In
      order to progress the search for biological markers and effective treatments,
      essential features need to be operationalized and broadly used in order to
      increase the probability that individuals included in samples have the same
      underlying illness.

PMID- 27047236
TI  - First description of the female of the jumping spider Balmaceda nigrosecta Mello
      Leitao (Salticidae, Dendryphantini, Marpissina).
AB  - The female of Balmaceda nigrosecta Mello-Leitao, 1945 is described and
      illustrated for the first time. In addition, this paper further illustrates the
      male, and provides the first known observations on the natural history of this
      species, including habitat, cohabitation, and prey capturedata. 

PMID- 27047237
TI  - Bambusimukaria, a new bamboo-feeding leafhopper genus from China, with
      description of one new species (Hemiptera, Cicadellidae, Deltocephalinae,
      Mukariini).
AB  - A new genus and species, Bambusimukaria quinquepunctata gen. & sp. n., feeding on
      bamboo in Guizhou and Fujian, China, are described and illustrated. The
      characters of crown, frontoclypeus, forewing venations and male genitalia place
      the new genus in the tribe Mukariini. 

PMID- 27047238
TI  - New species of subgenus Tipula (Sivatipula) from China, with redescription of T.
      (S.) parvauricula and a key to all known species of the Oriental Region (Diptera,
      Tipulidae, Tipula).
AB  - Species of Tipula (Sivatipula) biprocessa sp. n. from Guangxi, China is described
      and illustrated as new in the subgenus Tipula (Sivatipula) Alexander, 1964.
      Tipula (Sivatipula) parvauricula Alexander, 1941 is redescribed and illustrated
      based on additional morphological characters. Semen pump of this subgenus is
      discussed. A key to all described species in this group is compiled. 

PMID- 27047239
TI  - Uncovering the diversity in the Amazophrynella minuta complex: integrative
      taxonomy reveals a new species of Amazophrynella (Anura, Bufonidae) from southern
      Peru.
AB  - A new species of the genus Amazophrynella (Anura, Bufonidae) is described from
      the departments of Madre de Dios, Cusco and Junin in Peru. An integrative
      taxonomy approach is used. A morphological diagnosis, morphometrics comparisons,
      description of the advertisement call, and the phylogenetic relationships of the
      new species are provided. Amazophrynella javierbustamantei sp. n. differs from
      other species of Amazophrynella by: intermediate body-size (snout-vent length
      14.9 mm in males, n = 26 and 19.6 mm in females, n = 20), tuberculate skin
      texture of body, greatest hand length of the Amazophrynella spp. (3.6 mm in
      males, n = 26 and 4.6 mm in females, n = 20), venter coloration yellowish, tiny
      rounded black points covering the venter, and thirteen molecular autapomorphies
      in the 16S RNA gene. Its distribution varies from 215 to 708 m a.s.l. This
      discovery highlights the importance of the remnant forest in preserving the
      biodiversity in Peru, and increase in seven the species formally described in the
      genus Amazophrynella. 

PMID- 27047240
TI  - A checklist of helminth parasites of Elasmobranchii in Mexico.
AB  - A comprehensive and updated summary of the literature and unpublished records
      contained in scientific collections on the helminth parasites of the
      elasmobranchs from Mexico is herein presented for the first time. At present, the
      helminth fauna associated with Elasmobranchii recorded in Mexico is composed of
      132 (110 named species and 22 not assigned to species), which belong to 70 genera
      included in 27 families (plus 4 incertae sedis families of cestodes). These data
      represent 7.2% of the worldwide species richness. Platyhelminthes is the most
      widely represented, with 128 taxa: 94 of cestodes, 22 of monogeneans and 12 of
      trematodes; Nematoda and Annelida: Hirudinea are represented by only 2 taxa each.
      These records come from 54 localities, pertaining to 15 states; Baja California
      Sur (17 sampled localities) and Baja California (10), are the states with the
      highest species richness: 72 and 54 species, respectively. Up to now, 48
      elasmobranch species have been recorded as hosts of helminths in Mexico; so,
      approximately 82% of sharks and 67% of rays distributed in Mexican waters lack
      helminthological studies. The present list provides the host, distribution (with
      geographical coordinates), site of infection, accession number in scientific
      collections, and references for the parasites. A host-parasite list is also
      provided. 

PMID- 27047241
TI  - Additions to the Limoniidae and Pediciidae fauna of Morocco, with an updated
      checklist (Diptera, Tipuloidea).
AB  - Eighteen species of Limoniidae and two species of Pediciidae are recorded for the
      first time in Morocco, of which 15 species are new to North Africa. An updated
      checklist of Moroccan short-palped craneflies (Limoniidae and Pediciidae) is
      appended, containing 73 species in 25 genera. 

PMID- 27047242
TI  - First Alaskan records and a significant northern range extension for two species
      of Diplura (Diplura, Campodeidae).
AB  - Species in the class Diplura are recorded from Alaska for the first time. Two
      species, Tricampa rileyi Silvestri from Dall and Prince of Wales Islands in the
      Alexander Archipelago of Southeast Alaska and Metriocampa allocerca Conde &
      Geeraert from near Quartz Lake, southeast of Fairbanks, both in the family
      Campodeidae, are documented based on recently collected specimens deposited in
      the University of Alaska Museum Insect Collection. A brief review of the history
      of the documentation of the Alaskan soil microarthropod fauna is provided, as
      well as discussion of possible glacial refugia. 

PMID- 27047243
TI  - Chordodes ferox, a new record of horsehair worms (Nematomorpha, Gordiida) from
      South Africa.
AB  - Three females and one male specimen of a previously unconfirmed species of
      horsehair worms (Nematomorpha) from South Africa are described using Scanning
      Electron Microscopy. The females correspond to the description of Chordodes ferox
      Camerano, 1897, a species previously described from the Democratic Republic of
      the Congo (Congo-Kinshasa) and an adjacent, not further specified region of the
      Republic of Congo (Congo-Brazzaville). Characteristic is the presence of enlarged
      and elevated simple areoles around the base of a thorn areole, in combination
      with further cuticular characters. This is the latest of a total of six species
      of horsehair worms reported from South Africa so far. Two species of praying
      mantids, Polyspilota aeruginosa (Goeze, 1778) and Sphodromantis gastrica Stal,
      1858, have been identified as hosts of Chordodes ferox, while its distribution
      range in the region and the period of adult emergence from the host remain
      largely unknown. 

PMID- 27047244
TI  - Review of species of the genus Adelurola Strand, 1928, with a key to species
      (Hymenoptera, Braconidae, Alysiinae).
AB  - The alysiine genus Adelurola Strand, 1928 (Hymenoptera, Braconidae) is revised.
      Illustrated re-descriptions and a key to all known species of this genus are
      given. The following new combination is proposed: Dapsilarthra eurys (Chen & Wu,
      1994), comb. n. Adelurola amplidens (Fischer, 1966) and Adelurola asiatica
      Telenga, 1935 are recorded for the first time from Iran and Kyrgyzstan,
      respectively. 

PMID- 27047245
TI  - Revision of the genus Menevia Schaus, 1928 (Lepidoptera, Mimallonoidea,
      Mimallonidae) with the description of 11 new species.
AB  - The Neotropical genus Menevia Schaus, 1928 is revised to include 18 species, 11
      of which are new. Two species, Menevia ostia comb. n. and Menevia parostia comb.
      n. are transferred from Pamea Walker, 1855 to Menevia. Four species-groups are
      diagnosed for the first time based on external characters and male genitalia
      morphology. The following new species are described: Menevia rosea sp. n.,
      Menevia torvamessoria sp. n., Menevia magna sp. n., Menevia menapia sp. n.,
      Menevia mielkei sp. n., Menevia australis sp. n., Menevia vulgaris sp. n.,
      Menevia franclemonti sp. n., Menevia vulgaricula sp. n., Menevia cordillera sp.
      n., and Menevia delphinus sp. n.. A neotype is designated for Mimallo plagiata
      Walker, 1855, which has since been placed in Menevia. Mimallo saturata Walker,
      1855 is interpreted to be a nomen dubium. 

PMID- 27047246
TI  - Three new genera of Neotropical Mimallonidae (Lepidoptera, Mimallonoidea,
      Mimallonidae) with descriptions of three new species.
AB  - Three new genera of Mimallonidae are described. The monotypic genus Tostallo gen.
      n. is erected to contain "Perophora" albescens Jones, 1912, which was previously
      placed in the preoccupied genus Perophora Harris, 1841 and was never formally
      moved to a valid genus. Perophora is a junior homonym of Cicinnus Blanchard,
      1852, but the name albescens is not appropriately placed in Cicinnus due to
      external and genitalia characteristics entirely unique to the species albescens.
      The female of Tostallo albescens comb. n. is described and both sexes are figured
      for the first time. Auroriana gen. n. is erected to contain Auroriana
      florianensis (Herbin, 2012), comb. n. previously described as Cicinnus
      florianensis, and two new species: Auroriana colombiana sp. n. from Colombia and
      Auroriana gemma sp. n. from southeastern and southern Brazil. The female of
      Auroriana florianensis is described and figured for the first time. Finally, the
      monotypic genus Micrallo gen. n. is erected to include a new species, Micrallo
      minutus sp. n. described from northeastern Brazil. 

PMID- 27047247
TI  - Taxonomic hypotheses regarding the genus Gerbillus (Rodentia, Muridae,
      Gerbillinae) based on molecular analyses of museum specimens.
AB  - Methodological improvements now allow routine analyses of highly degraded DNA
      samples as found in museum specimens. Using these methods could be useful in
      studying such groups as rodents of the genus Gerbillus for which i) the taxonomy
      is still highly debated, ii) collection of fresh specimens may prove difficult.
      Here we address precise taxonomic questions using a small portion of the
      cytochrome b gene obtained from 45 dry skin/skull museum samples (from 1913 to
      1974) originating from two African and three Asian countries. The specimens were
      labelled Gerbillus gerbillus, Gerbillus andersoni, Gerbillus nanus, Gerbillus
      amoenus, Gerbillus perpallidus and Gerbillus pyramidum, and molecular results
      mostly confirmed these assignations. The close relationship between Gerbillus
      nanus (Asian origin) and Gerbillus amoenus (African origin) confirmed that they
      represent vicariant sibling species which differentiated in allopatry on either
      side of the Red Sea. In the closely related Gerbillus perpallidus and Gerbillus
      pyramidum, specimens considered as belonging to one Gerbillus pyramidum
      subspecies (Gerbillus pyramidum floweri) appeared closer to Gerbillus perpallidus
      suggesting that they (Gerbillus pyramidum floweri and Gerbillus perpallidus) may
      represent a unique species, distributed on both sides of the Nile River, for
      which the correct name should be Gerbillus floweri. Furthermore, the three other
      Gerbillus pyramidum subspecies grouped together with no apparent genetic
      structure suggesting that they may not yet represent genetically differentiated
      lineages. This study confirms the importance of using these methods on museum
      samples, which can open new perspectives in this particular group as well as in
      other groups of interest. 

PMID- 27047248
TI  - EDITORIAL Implication of Non-coding RNAs in Cancer Biology and Cellular
      Physiology.

PMID- 27047249
TI  - Non-coding RNAs in Exosomes: New Players in Cancer Biology.
AB  - Exosomes are lipid bilayer extracellular vesicles (EVs) of 50-150nm in size,
      which contain nucleic acids (mRNA, ncRNAs and DNA), proteins and lipids. They are
      secreted by all cells and circulate in all body fluids. Exosomes are key
      mediators of several processes in cancer that mediate tumor progression and
      metastasis. These nano-vesicles, when secreted from cancer cells, are enriched in
      non-coding RNAs (e.g. microRNAs) complexed with the RNA-Induced Silencing Complex
      (RISC), that mediate an efficient and rapid silencing of mRNAs at the recipient
      cell, reprogramming their transcriptome. MicroRNAs in circulation encapsulated in
      exosomes are protected from degradation by a lipid bilayer and might serve as
      potential non-invasive diagnostic and screening tools to detect early stage
      cancer, to facilitate treatment options and possible help in curative surgical
      therapy decisions. Additionally, engineered exosomes can be used as therapy
      vehicles for targeted delivery of RNAi molecules, escaping the immune system
      detection. 

PMID- 27047250
TI  - miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma.
AB  - Malignant gliomas are lethal primary intracranial tumors. To date, little
      information on the role of deregulated genes in gliomas have been identified. As
      the involvement of miRNAs in the carcinogenesis is well known, we carried out a
      pilot study to identify, as potential biomarkers, differentially expressed
      microRNAs in blood samples of patients affected by glioma. We studied the miRNAs'
      expression, by means of microarray and Real-Time PCR, in 30 blood samples from
      glioma patients and in 82 blood samples of patients suffering from: (a) various
      neurological disorders (n=30), (b) primary B-lymphoma of the Central Nervous
      System (PCNSL, n=36) and (c) secondary brain metastases (n=16). By quantitative
      real time reverse-transcriptase polymerase chain reaction (qRT-PCR), we
      identified significantly increased levels of two candidate biomarkers, miR-15b
      and miR-21, in blood of patients affected by gliomas. ROC analysis of miR-15b
      biomarker levels allowed to differentiate patients with tumour from patients
      without glioma. Furthermore, combined expression analyses of miR15b and miR-21
      distinguished between patients with and without glioma (90% sensitivity and 100%
      specificity). In addition, a decrement in the expression levels of miR-16
      characterized glioblastomas compared to low grade and anaplastic gliomas. In
      conclusion, this pilot study suggest that it's possible to identify the disease
      state by meaning miR-15b and miR-21 markers in blood, while miR-16 can be used to
      distinguish glioblastoma from other grade gliomas. They can potentially be used
      as biomarkers for non-invasive diagnosis of gliomas; further studies are
      mandatory to confirm our preliminary findings. 

PMID- 27047251
TI  - Circular RNAs in Eukaryotic Cells.
AB  - Circular RNAs (circRNAs) are now recognized as large species of transcripts in
      eukaryotic cells. From model organisms such as C. elegans, Drosophila, mice to
      human beings, thousands of circRNAs formed from back-splicing of exons have been
      identified. The known complexity of transcriptome has been greatly expanded upon
      the discovery of these RNAs. Studies about the biogenesis and physiological
      functions have yielded substantial knowledge for the circRNAs, and they are now
      more likely to be viewed as regulatory elements coded by the genome rather than
      unavoidable noise of gene expression. Certain human diseases may also relate to
      circRNAs. These circRNAs show diversifications in features such as sequence
      composition and cellular localization, and thus we propose that they may be
      divided into subtypes such as cytoplasmic circRNAs, nuclear circRNAs, and exon
      intron circRNAs (EIciRNAs). Here we summarize and discuss knowns and unknowns for
      these RNAs, and we need to keep in mind that the whole field is still at the
      beginning of exciting explorations. 

PMID- 27047252
TI  - Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy.
AB  - Non-coding RNA refers to a large group of endogenous RNA molecules that have no
      protein coding capacity, while having specialized cellular and molecular
      functions. They possess wide range of functions such as the regulation of gene
      transcription and translation, post-transcriptional modification, epigenetic
      landscape establishment, protein scaffolding and cofactors recruitments. They are
      further divided into small non-coding RNAs with size < 200nt (e.g. miRNA, piRNA)
      and long non-coding RNAs with size >= 200nt (e.g. lincRNA, NAT). Increasing
      evidences suggest that both non-coding RNAs groups play important roles in cancer
      development, progression and pathology. Clinically, non-coding RNAs aberrations
      show high diagnostic and prognostic values. With improved understanding of the
      nature and roles of non-coding RNAs, it is believed that we can develop
      therapeutic treatment against cancer via the modulation of these RNA molecules.
      Advances in nucleic acid drug technology and computational simulation prompt the
      development of agents to intervene the malignant effects of non-coding RNAs. In
      this review, we will discuss the role of non-coding RNAs in cancer, and evaluate
      the potential of non-coding RNA-based cancer therapies. 

PMID- 27047253
TI  - RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load.
AB  - The review intends to present and recapitulate the current knowledge on the roles
      and importance of regulatory RNAs, such as microRNAs and small interfering RNAs,
      RNA binding proteins and enzymes processing RNAs or activated by RNAs, in cells
      infected by RNA viruses. The review focuses on how non-coding RNAs are involved
      in RNA virus replication, pathogenesis and host response, especially in
      retroviruses HIV, with examples of the mechanisms of action, transcriptional
      regulation, and promotion of increased stability of their targets or their
      degradation. 

PMID- 27047254
TI  - MicroRNAs in Myeloid Hematological Malignancies.
AB  - MicroRNAs are 19-24 nucleotides noncoding RNAs which silence modulate the
      expression of target genes by binding to the messenger RNAs. Myeloid malignancies
      include a broad spectrum of acute and chronic disorders originating from from the
      clonal transformation of a hematopoietic stem cell. Specific genetic
      abnormalities may define myeloid malignancies, such as translocation t(9;22) that
      represent the hallmark of chronic myeloid leukemia. Although next-generation
      sequencing pro-vided new insights in the genetic characterization and
      pathogenesis of myeloid neoplasms, the molecular mechanisms underlying myeloid
      neoplasms are lacking in most cases. Recently, several studies have demonstrated
      that the expression levels of specific miRNAs may vary among patients with
      myeloid malignancies compared with healthy individuals and partially unveiled how
      miRNAs participate in the leukemic transformation process. Finally, in vitro
      experiments and pre-clinical model provided preliminary data of the safety and
      efficacy of miRNA inhibitory molecules, opening new avenue in the treatment of
      myeloid hematological malignancies. 

PMID- 27047256
TI  - Neutrophil MiRNA-128-3p is Decreased During Active Phase of Granulo-matosis with
      Polyangiitis.
AB  - Granulomatosis with polyangiitis is a rare chronic inflammatory disease. In this
      multisystem autoimmune disorder neutrophils cause small vessels necrosis and
      infiltrate perivascular tissue to form granulomas. Progression of the disease is
      evaluated by the symptoms score and by a titer of anti-neutrophil cytoplasm
      antibodies. Despite glucocorticoid and immunosuppressive therapy, prognosis is
      complicated by chronic renal insufficiency, hearing loss and skin ulceration. In
      this preliminary study we tested the hypothesis that altered neutrophil
      expression of miRNAs can contribute to the cell activation, extracellular traps
      formation and decreased apoptosis. First we compared a profile of 728 miRNAs
      expressed in circulating neutrophils of patients with active disease and matched
      healthy donors. Subsequently, candidate miRNAs were quantified in neutrophils
      from 16 subjects with active disease, 16 asymptomatic patients at the remission
      and in 16 healthy controls. Out of 11 candidate miRNAs, only miR-128-3p was both
      biologically (relative quantity < 30% control or remission patients) and
      statistically (p<0.01) decreased in the cells during active stage of the disease.
      This miRNA correlated with a clinical score of the disease well. A set of 10
      transcripts involved in the mechanism of the disease was quantified from the same
      neutrophils RNA. Relative expression of MMP9 was higher in neutrophils from the
      patients with active disease and correlated negatively with miR-128-3p. The
      opposite finding was present for MTA1 transcripts. Despite surprisingly scarce
      changes in the expression of neutrophil miRNAs, miR-128-3p is the best candidate
      for deciphering etiology of granulomatosis with polyangiitis. 

PMID- 27047255
TI  - MicroRNAs in Lymphoma: Regulatory Role and Biomarker Potential.
AB  - Although it is now evident that microRNAs (miRNAs) play a critical regulatory
      role in many, if not all, pathological and physiological processes, remarkably
      they have only formally been recognized for less than fifteen years. These
      endogenously produced short non-coding RNAs have created a new paradigm of gene
      control and have utility as both novel biomarkers of cancer and as potential
      therapeutics. In this review we consider the role of miRNAs in lymphoid biology
      both under physiological (i.e. lymphopoiesis) and malignant (i.e.
      lymphomagenesis) conditions. In addition to the functional significance of
      aberrant miRNA expression in lymphomas we discuss their use as novel biomarkers,
      both as a in situ tumour biomarker and as a non-invasive surrogate for the tumour
      by testing miRNAs in the blood of patients. Finally we consider the use of these
      molecules as potential therapeutic agents for lymphoma (and other cancer)
      patients and discuss some of the hurdles yet to be overcome in order to translate
      this potential into clinical practice. 

PMID- 27047257
TI  - Azadioxatriangulenium: Synthesis and Photophysical Properties of Reactive Dyes
      for Bioconjugation.
AB  - Azadioxatriangulenium (ADOTA) is a fluorescent triangulenium dye with a long
      fluorescence lifetime, highly polarized transitions and emission in the red part
      of the visible spectrum. These properties make the chromophore suited for
      application in fluorescence polarization/anisotropy assay. To be useful for these
      applications, reactive forms of the dyes must be available in significant
      quantities. Here, the synthesis and photophysical properties of amine-reactive
      NHS esters and a thiol-reactive maleimide derivate of ADOTA are reported. The
      synthesis involves two steps of nucleophilic bridge forming reactions starting
      from tris(2,6-dimethoxyphenyl) methylium tetrafluoroborate, which can readily be
      made on 100 gram scale. In the third and final step the reactive NHS or maleimide
      groups are formed. The beneficial photophysical properties of the ADOTA
      chromophore are maintained in these derivatives, and we conclude that these
      systems are ideal to study protein motion and protein-protein interactions for
      systems of up towards 1000 kDa.

PMID- 27047258
TI  - META-ANALYSIS OF THE SCIENTIFIC CONTENTS OF MATERIA SOCIO-MEDICA JOURNAL IN THE
      PERIOD 2009-2015.
AB  - INTRODUCTION: Materia Socio Medica Journal has a long history. It was founded in
      1978. AIM: To evaluate journal articles in 2015 and compare findings to previous
      years. MATERIAL AND METHODS: The study has retrospective and descriptive
      character, and included the period 2009-2015. RESULTS: A total of 99 articles
      were published in Materia Socio Medica during 2015 and it shows an upward trend
      during the period 2009-2015. Original articles are present in majority during the
      last seven years (69,2%). Analyzing the last seven years, 44,1% of articles were
      from the field of clinical medicine. Articles from the fields of public health
      show an upward trend during the last four years. Collaboration rate in 2015 was
      0,95. Authors of the articles are from ten countries (four continents). H index
      of journal is 8 and g index is 12 (Publish or Perish software). According to
      GoogleScholar, h5 index for Materia Socio Medica is 8 and h5 median is 9.
      CONCLUSIONS: The objectives of the journal in the next year are: to become a part
      of the Scopus and Web of Science databases, further internationalization and
      promotion of the journal in the country and the region, revision and broadening
      of the Editorial Board, trying to follow trend in reducing the number of days
      required for a decision on acceptance or revision of article and involvement of
      the younger generation of professionals and scientists into the journal work and
      publishing scope, which will lead to emergence of new enthusiasm and ideas
      (Journal intends to follow the trends of modern biomedical publishing worldwide).

PMID- 27047259
TI  - NON-COMMUNICABLE CHRONIC DISEASES RISK PREVALENCE OF FAMILY MEDICINE PATIENTS IN
      THE FEDERATION OF BOSNIA AND HERZEGOVINA.
AB  - AIM: The aim of this study is to represent the prevalence of non-communicable
      diseases risks among patients of family medicine practices in the Federation of
      Bosnia and Herzegovina. Risks prevalence was obtained from an organized massive
      screening being performed by 100 family medicine teams in four cities of the
      Federation of B&H during 2013. MATERIAL AND METHODS: Our concept of "preventive
      treatment of a patient" included detecting and monitoring the following chronic
      non-communicable diseases risk factors: (a) hypertension; (b) obesity; (c)
      smoking; (d) physical inactivity; and (e) dyslipidemia; (f) diabetes mellitus.
      Our sample of examined patients was 46.638. RESULTS: Highest risk prevalence
      within entire F B&H is observed for dyslipidemia (90.3%) and physical inactivity
      (64.7%). Lowest prevalence was found for blood sugar and hypertension at 19.2%
      and 21.6%, respectively. Smoking prevalence of the examined patients was 28.4%.
      Prevalence of the obesity as health risk (ITM > 30) was 25.5 %. It is of interest
      that statistically significant differences of individual risk prevalence among
      cities are evident. Risk distribution among cities ranked from highest to lowest
      prevalence, shows clearly that Sarajevo is leading in four risks compared to the
      other cities, while Zenica is ranked lowest for four risk factors. The examined
      population of the four cities can be ranked from lowest to highest prevalence of
      the examined risk factors as follows: Sarajevo, Mostar, Tuzla, and Zenica.

PMID- 27047260
TI  - DISTRESS AND PTSD IN PATIENTS WITH CANCER: COHORT STUDY CASE.
AB  - INTRODUCTION: embarrassed emotional experience may affect the ability to oncology
      patient effectively cope with cancer, symptoms and treatment. Distress extends a
      long period, from common, normal feelings of vulnerability, sadness and fears to
      problems of PTSD, depression, anxiety, panic, social isolation and the perception
      of spiritual crisis. The aim of the research is to determine the level of
      distress and PTSD in cancer patients. PATIENTS AND METHODS: In a prospective,
      cohort study cases from 2011- 2014 were included patients with cancer who are
      treated under the supervision of his chosen family medicine doctor. Including a
      factor for the participation of patients in the study is that from the moment of
      diagnosis of malignant disease passed <12 months. The total sample was 174 of the
      planned 200 (response rate=87%). The subjects were divided into three groups. A
      key factor in the creation of the group was the time elapsed from the moment of
      acknowledgment and confirmation of the diagnosis: T1 <14 days, n=56 patients;
      T2>14 days-<6 months, n=79 patients; T3>6 months n=39 patients. To achieve the
      set goals of the research was used instruments of 3 questionnaires: Questionnaire
      on the clinical characteristics of patients with malignant disease, demographic
      and individual characteristics; questionnaire distress oncology patient-hospital
      scales of depression and anxiety, HADS scale (Hospital Anxiety and Depression
      Scale - HADS) and a rapid test for self-assessment of the symptoms of PTSD.
      RESULTS: Age of patients was 54.63 +/- 11:46 years, and the age of the
      respondents when they were diagnosed with cancer 54.34 +/- 11.26 years. The
      prevalence of distress was a high 76% 82x higher than expected), and PTSD 55%.
      Predictors of burnout syndrome in cancer patients are all important determinants
      of malignant disease: the time elapsed since the diagnosis of the disease which
      determines the clinical status of malignant disease (beta=0.280; P=0.001; 95% CI,
      0742-2259), discovered metastases (beta=0.304; P=0.001; 95% CI -2621 to 0978) and
      treatments (beta=0.160; P=0.031, 95% CI 0050 to 1.060). CONCLUSION: The problem
      of distress in cancer patients is widespread and has a high prevalence of 76% in
      our environment, while still absent intervention and treatment.

PMID- 27047261
TI  - INVESTIGATION OF BACTERIOLOGICAL INFECTIONS OF THE AMERICAN COCKROACHES IN PAVEH
      CITY, KERMANSHAH PROVINCE.
AB  - INTRODUCTION: American cockroaches, Periplaneta americana, are the most important
      pests in hospitals and dwelling environments. They are mechanical vectors of some
      bacterial pathogens. GOAL: The present investigation was carried out in Ghods
      hospital and 5 dwelling localities of Paveh city to evaluate bacterial
      infestations of American cockroaches in this region of Iran. METHODS: The samples
      were randomly collected from hospital environments and toilets and kitchens of
      the dwelling localities from December-March 2012 and July-September 2013. The
      samples were captured using sterile test tubes and sterile hand gloves. RESULTS:
      Totally, 98 cockroaches were collected from hospital (45.9%) and dwelling (54.1%)
      environments. Eight groups of bacteria including: Pseudomonas spp., Proteus spp.,
      Klebsiella spp., Staphylococcus spp., Bacillus spp., Serratia spp., Entrobacter
      spp. and Escherichia coli were extracted. CONCLUSIONS: The findings of the
      present study revealed that the American cockroaches are very important in
      transmission of some bacterial pathogens, so health education and using the
      effective control methods to elimination and reduction of cockroaches are
      necessary.

PMID- 27047262
TI  - THE EFFECT OF OUTPATIENT SERVICE QUALITY ON PATIENT SATISFACTION IN TEACHING
      HOSPITALS IN IRAN.
AB  - AIM: The quality of services plays a primary role in achieving patient
      satisfaction. The main purpose of this study was to explore the effect of
      outpatient service quality on patient satisfaction in teaching hospitals in Iran.
      METHODS: this cross-sectional study was conducted in 2014. The study sample
      included 500 patients were selected with systematic random method from the
      outpatient departments (clinics) of four teaching hospitals in Tehran. The survey
      instrument was a questionnaire consisted of 44 items, which were confirmed its
      reliability and validity. The data were analyzed by using descriptive statistics,
      Pearson's correlation, and multivariate regression methods with the SPSS.18
      software. RESULTS: According to the findings of this study, the majority of
      patients had a positive experience in the outpatient departments of the teaching
      hospitals and thus evaluated the services as good. Perceived service costs,
      physician consultation, physical environment, and information to patient were
      found to be the most important determinants of outpatient satisfaction.
      CONCLUSION: The results suggest that improving the quality of consultation,
      providing information to the patients during examination and consultation,
      creating value for patients by reducing costs or improving service quality, and
      enhancing the physical environment quality of the clinic can be regarded as
      effective strategies for the management of teaching hospitals toward increasing
      outpatient satisfaction.

PMID- 27047263
TI  - THE RELATIONSHIP BETWEEN HOFSTEDE ORGANIZATIONAL CULTURE AND EMPLOYEES JOB
      BURNOUT IN HOSPITALS OF TEHRAN UNIVERSITY OF MEDICAL SCIENCES 2014-2015.
AB  - OBJECTIVE: Organizational culture plays a supportive role in modification of
      structure and implementation of new management systems. So, the management of
      organizational culture with cultural elements recognition plays an important role
      in improving the efficacy and effectiveness of the organization. On the other
      hand, the health sector requires healthy and motivated practitioners and staff to
      achieve these goals. Job burnout as a response to environmental stressors causes
      some changes in attitude and behavior towards work and work environment, and
      factors such as organizational culture effect on it. This study aimed to clarify
      the relationship between organizational culture and employee's burnout. MATERIAL
      AND METHODS: This is a descriptive and cross-sectional study. The study
      population included all clinical staff (physicians and nurses) and nonclinical
      (administrative and financial) in hospitals affiliated to Tehran University of
      Medical Sciences in 2014-2015. Among them, 387 participants were selected using
      simple stratified random sampling. In order to collect the required data, the
      Maslach Burnout Inventory (1981) and Hofstede's organizational cultural
      questionnaire (1988) were used. Also Cronbach's alpha obtained 0.836 and 0.913
      for them, respectively. In order to analyze the data, the Kolmogorov-Smirnov
      test, multiple regression, independent t-test and binomial test were performed
      using SPSS 20. RESULTS: Results showed that organizational culture in studied
      population were masculine, collectivism with high uncertainty avoidance and
      relatively equitable power distance. Mean score for emotional exhaustion was
      (31.4) and most of participants 315 (40.6%) had average emotional exhaustion.
      Mean score for depersonalization was (21.16) and most of participants 315 (82.1%)
      had high depersonalization. Mean score for personal accomplishment was (30.02)
      and most of participants 280 (73.2%) had high personal accomplishment. Multiple
      correlation coefficient showed that there is a significant relationship between
      the components of organizational culture including masculinity/femininity,
      individualism/collectivism, uncertainty avoidance and power distance with job
      burnout (r=0.305, p>0.001). R(2) also showed that 9.3 percent of the variance of
      job burnout is related to the mentioned factors. CONCLUSION: The overall result
      is that some staff health issues rooted in their culture; so, the organizational
      culture assessment by hospital managers to plan and goals achievement is
      essential. If necessary, improving organizational culture, creating a healthy
      environment, enhancing tolerance and individual adjustment and stress control can
      help to reduce staff burnout.

PMID- 27047264
TI  - LOW PRETERM BIRTH RATE WITH DECREASING EARLY NEONATAL MORTALITY IN BOSNIA AND
      HERZEGOVINA DURING 2007-2014.
AB  - THE AIM: of the study was to determine the situation of preterm births and early
      neonatal mortality during 2007-2014 in Tuzla Canton, Bosnia and Herzegovina.
      METHODS: The study covers a 8-year period and is based on the protocols at the
      Tuzla Clinic for Gynecology and Obstetrics that covers all birth in Tuzla Canton
      area. We analyzed the gestational age of all newborns and recorded the number of
      neonatal deaths in the first week after birth. Demographics, pregnancy and birth
      characteristics were collected from the maternal records. RESULTS: The total
      number of births in the period was 32738. Preterm birth was identified in 2401
      (7.3%) cases with 12,5% occurring before 32 gestational weeks and 64% in 35-36
      gestational weeks. The mothers of the 24-31 gws preterm group were significantly
      younger that those in the 32-36 group. In the 32-36 group there were
      significantly greater proportions of mothers with assisted reproductive
      technology and pre-eclampsia and 16.7% was medical induced preterm births versus
      11.4 % in the 24-31 PTB group, p<0.05. The incidence of PTB did no vary
      significantly during the period, the lowest rate was found in 2010 (6.4%). A
      total of 221 children died giving a early mortality rate of 6.8 per 1000 live
      born over the 8 years. The majority 156 dying infants (70.6%) were preterm, only
      5.7% died being born in the 35-36 gestational week (5.9 per 1000). Overall the
      preterm early mortality (7.3 per 1000) has shown a decreasing tendency during the
      latter years. CONCLUSION: During the last 8 years there have been no significant
      decline in preterm birth in the Tuzla region while a decline in early neonatal
      death has been registered.

PMID- 27047265
TI  - POSTOPERATIVE PAIN: MANAGEMENT AND DOCUMENTATION BY IRANIAN NURSES.
AB  - BACKGROUND: Pain is one of the most common symptoms experienced by patients after
      surgeries. Inadequate postoperative pain management is an international problem
      and the need to improve its management is well documented. The aim of the study
      was to assess nursing reports related to the patients' pain intensity and
      quality, concomitant symptoms, use of scales in pain assessment, and compliance
      with the national guideline after surgery. METHODS: This study was a
      retrospective cohort; samples were nurse records of patients who had elective
      surgery. RESULT: Only 6% of the patients' pain records included pain intensity
      which was not measured with standard scales. More than half of all injections
      were opioid analgesic which is in contrast to the guidelines of the Iranian
      Ministry of Health. Pain assessment was higher in women and by nurses with more
      than 15 years of working experience. CONCLUSION: to conclude, the patients' pain
      was not assessed properly in terms of intensity, quality, and associated
      symptoms. Therefore, training and motivating nurses is very important in this
      context and should be incorporated in nurses' academic and continuous educational
      courses.

PMID- 27047266
TI  - ASSOCIATION BETWEEN SELF-CARE BEHAVIORS AND SELF-ESTEEM OF RURAL ELDERLIES;
      NECESSITY OF HEALTH PROMOTION.
AB  - INTRODUCTION: Changes in the modern medical science caused significant reduction
      of mortality and every day increase of the elderly in the world. According to
      prevalence of physical and mental problems in elderly, it is necessary to take
      some actions. Self care in one of the best way to improve elderly health and life
      satisfaction that seems have a relation to self-esteem. METHODS: This descriptive
      and analytical study was performed on 180 elderly in rural areas of the Sari
      city. Elderly selected by multi-stage randomize sampling method. Data were
      gathered by using standard questionnaires of self-care and Rosenberg self-esteem.
      Data were analyzed by Spearman and Pearson's correlation using SPSS software
      (V16). FINDINGS: The mean+/-SD of the ages of the elderly were 66.85+/-7.661. The
      score of self-care varies between 99 to 155 and most of them (66.7%) had good
      level of self-care. Also, most of elderly (52.2%) had high level of self-esteem.
      Also there was a significant relationship, between self-care and self-esteem
      (P<0.001, r=0.426). CONCLUSION: According to significant relationship between
      self-care and self-esteem of elderly, by the planning for improving the self care
      of elderly, can increase their health and significantly reduce from physical and
      mental complications.

PMID- 27047267
TI  - INSTRUMENTS OF HIGH RISK SEXUAL BEHAVIOR ASSESSMENT: A SYSTEMATIC REVIEW.
AB  - BACKGROUND: Sexual behavior is a complex activity affecting all aspects of
      human's life. Risky sexual behaviors impose negative outcomes on family,
      relationships and health. Unsafe sex is the second most leading cause of
      disability adjusted life years worldwide. Valid and reliable tools for assessment
      of risky sexual behaviors are necessary for implementing preventive measures.
      METHODS: we searched Medline and the Cochrane Library of Systematic Reviews, with
      the keywords of "risky sexual behavior assessment", "sexual risk assessment",
      "high risk sexual behavior", "sexual risk taking". By reviewing references of the
      articles, some complementary studies were added. RESULTS: Assessment can be
      performed by questionnaire or non-questionnaire instruments. Questionnaires vary
      depending on their target population, evaluation of risky sexual behavior as a
      whole or focusing on an associated risk factor. In order to avoid usual biases in
      self reports, objective biomarker assessment of unprotected sex are employed.
      These markers include prostate specific antigen, chromosome Y DNA and
      Seminogelin. CONCLUSION: Risky sexual behavior can be assessed by various
      subjective and objective methods. While self-reports are more feasible, objective
      methods offer a higher degree of reliability. Further studies for finding more
      feasible methods of using biomarkers are recommended.

PMID- 27047268
TI  - ANALYSIS OF THE CAUSES OF OCCUPATIONAL INJURIES AND APPLICATION OF PREVENTIVE
      MEASURES.
AB  - INTRODUCTION: Occupational injuries are one of the major public health problems
      in the world and in our country, and are the leading cause of mortality and
      morbidity of workers. The goals of this study are to determine the type and
      nature of occupational injuries and propose a program of preventive measures.
      MATERIAL AND METHODS: The study included 98 injured workers in the period from
      January 1, 2014 to December 31, 2014 in the area of the Cazin municipality. The
      sources of data used are reports of an accident at work in the Occupational
      Health Services and the Primary Health Care Center. RESULTS: The most common
      injuries are the ones by sharp object (30.6%), incarceration (27.5%) and fall
      from a height (19.3%). According to the nature of the injuries the most numerous
      are contusions and lacerations. Activities that are most prevalent among those
      injured are in service provision (48.0%), manufacturing (36.4%) and construction
      (33.3%). CONCLUSIONS: It is necessary to implement measures of collective and
      personal protection, education of workers, proper handling of tools and
      machinery, improving interpersonal relationships, rewarding and implementation of
      the strategy of making plans for the program of occupational safety.

PMID- 27047270
TI  - THE ROLE OF LACTATE CLEARANCE AS A PREDICTOR OF ORGAN DYSFUNCTION AND MORTALITY
      IN PATIENTS WITH SEVERE SEPSIS.
AB  - BACKGROUND: Little is known about biomarkers which are used to classification of
      patients in order to diagnosis severity of sepsis among clients of emergency
      units. It seems that Lactate's clearance can be used in this regard. This study
      aimed to determine the relationship between Lactate's clearance, mortality and
      organ's dysfunction with severe sepsis. MATERIALS AND METHODS: In this study 90
      patients with severe sepsis, were visited and examined exactly. Para clinical
      tests, serum venous lactate, organ's dysfunction scores, Acute Physiology and
      Chronic Health Evaluation II (APACHE-II) and Sequential Organ Failure Assessment
      (SOFA) were applied upon admission and 6 hours after it. According to clinical
      and laboratory criteria, dysfunction in main organs were examined and Lactate's
      Clearance was accounted. All the patients were cured according to early goal
      directed therapy protocol. RESULTS: Among the participants 49 and 41 were male
      and female respectively. The mean age of the group was 49.37+/-1.41. The patients
      were classified to groups, less or more than 10% lactate's clearance. Mortality
      rate of the patients was 18.9% (17 people). Mean age of the dead group was
      49.71+/-13.33. The mean of dysfunctional organs which is assessed in terms of
      clinical, laboratory and SOFA criteria was significantly higher among the dead
      group than other. The Lactate's clearance in the dead group was significantly
      lower than the other group (p<.05). CONCLUSION: It was concluded that patients
      with severe sepsis is a marker which is related to tissue hypoxia, also lactate's
      clearance increasing is related to drastic reduction in biomarkers, mortality,
      and incidence of organ's dysfunction. Overall, patients with lower lactate's
      clearance are counted a high risk group for mortality and organs' dysfunction.

PMID- 27047269
TI  - CONTRIBUTING FACTORS FOR DEVELOPMENT OF NECROTIZING ENTEROCOLITIS IN PRETERM
      INFANTS IN THE NEONATAL INTENSIVE CARE UNIT.
AB  - BACKGROUND: necrotizing enterocolitis is a serious condition that affects mostly
      preterm infants, with high mortality rate. AIM: to estimate the influence of
      potentially contributing factors of this multifactorial disease. METHODS: the
      study group included 51 necrotizing enterocolitis infants who were less than 37
      week gestation who were hospitalized in NICU during a five year period. The
      control group consisted of 71 patients with approximately the same gestational
      age and birth weight. Average gestational age in the study group was 30.2 weeks
      (SD 3.7), average birth weight 1502g (SD 781.5). Average postnatal age in the
      time of the presenting NEC was 18.2 days (SD 12.8). RESULTS: Logistic regression
      estimates the influence of risk factors, which in our study related to the
      treatment of preterm infants on the likelihood of NEC development. Our regression
      model consisted of seven independent variables (nosocomial infections, mechanical
      ventilation, nasal continuous positive pressure, morphine, inotropes, blood
      transfusions, and H2 blockers), which were shown to have a statistically
      significant impact, X2 (7, n=1222) = 49.522, p<0.0001; two independent variables
      (nosocomial infection and H2 blockers use) were statistically significant.
      Preterm infants with nosocomial infection had a three times greater chance of
      developing NEC, and infants who received H2 blockers had a 1.5 higher risk.
      CONCLUSIONS: Underlying pathology of very low birth weight infants and their
      treatment in NICU contribute to NEC development. Identifying risk factors can be
      crucial for the early diagnosis and outcome of disease. Awareness of risk factors
      should influence changes in practice to reduce the risk of NEC.

PMID- 27047271
TI  - THE FREQUENCY OF COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
      (CA-MRSA) AMONG SAMPLES IN INSTITUTE FOR PUBLIC HEALTH IN CANTON SARAJEVO.
AB  - BACKGROUND: The increase in the incidence of methicillin-resistant Staphylococcus
      aureus (MRSA) infections lacking risk factors for exposure to the health care
      system has been associated with the recognition of new MRSA clones known as
      community-associated MRSA (CA-MRSA). These strains have been distinguished from
      health care-associated MRSA (HA-MRSA) strains by epidemiological, molecular and
      genetic means as well as by antibiotic susceptibility profile, tissue tropism and
      virulence traits. OBJECTIVE: To assess prevalence and antibiotic susceptibility
      profile of CA-MRSA in Canton Sarajevo, Bosnia and Herzegovina. RESULTS: Out of
      1.905 positive Staphylococcus aureus isolates from various samples of outpatients
      collected during six months, 279 (14,64%) were MRSA isolates. Out of 279 MRSA
      samples, 133 (47,67%) were found in nasal swabs, from which 48 (36,09%) were in
      the age group <1 year and 39 (29,32 %) are in the age 1-5 year. Rate of the
      positive skin swabs was highest among the subject of age group <1 year (46 or
      54,12 %) and 1-5 year (18 or 21,18 %). Predominantly antibiotic types among MRSA
      strains are resistant to penicillin and cefoxitin (36,90 %) and to penicillin,
      cefoxitin and erythromycin (61,35 %). CONCLUSION: Continued monitoring of
      epidemiology and emerging drug resistance data is critical for the effective
      management of these infections.

PMID- 27047272
TI  - NUTRITIONAL THERAPY IN THE TREATMENT OF ACUTE CORROSIVE INTOXICATION IN ADULTS.
AB  - INTRODUCTION: Acute intoxications with corrosive substances can cause severe
      chemical injuries of the upper gastrointestinal tract, most often located in the
      mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute
      phase of intoxication, regenerative response may result in esophageal and/or
      gastric stenosis, and increased risk of esophageal and gastric cancer. Such
      intoxication may be fatal due to perforation or tracheal necrosis. Enteral
      nutrition is a nutritional method when nutritional substances are administered
      through specially designed tubing placed through the nose or percutaneously,
      directly into the GIT. AIM: The aim of this study is to describe the methods of
      artificial nutrition in patients with acute corrosive intoxications and the
      importance of nutritional support in the treatment of these intoxications.
      DISCUSSION: Nutrition in the treatment of acute corrosive intoxications is one of
      the most important therapeutic processes that largely contribute to faster
      recovery of the post-corrosive injuries of upper GIT, stabilization of biologic,
      immunologic and metabolic parameters, and reduction of length of stay in hospital
      Aim of the treatment of acute corrosive intoxications is to prevent perforation
      and progressive fibrosis, and esophageal and gastric stenosis. There are
      different and often conflicting positions, on the conservative treatment of acute
      corrosive intoxications in adults. Such treatment mainly consists of anti
      secretory treatment, antibiotics and intensive hyper-alimentation, aiming to
      prevent late post-corrosive intoxications. CONCLUSION: It is considered that
      nutritional support plays a major role in maintenance of metabolic processes and
      prevention of severe metabolic complications that could additionally aggravate
      the condition and impair the treatment.

PMID- 27047273
TI  - METABOLIC SYNDROME - THEORY AND PRACTICE.
AB  - INTRODUCTION: Due to sedentary lifestyles and excessive calorie intake, metabolic
      syndrome is becoming increasingly common health problem in the world, as well as
      in our country, and it is estimated to occur in 30% of the population of middle
      and older age. The metabolic syndrome is a combination of disorders that include:
      obesity, insulin resistance, glucose intolerance, impaired regulation of body fat
      and high blood pressure. Complications resulting from metabolic syndrome
      significantly reduces quality of patient's life and represents a huge socio
      economic burden. Metabolic syndrome therapy is directed to reduce all risk
      factors, and that means the change of lifestyle, which includes a reduction of
      body weight, physical activity, antiatherogenic diet and smoking cessation.
      Medical therapy is aimed to the individual risk factors. CASE REPORT: In case of
      our patient, despite the optimal standard therapy, including drugs for the
      regulation of LDL and HDL cholesterol and triglycerides, an intensive control of
      blood pressure and glucose, failure to implement the recommended treatment led to
      a myocardial infarction. CONCLUSION: The fundamental problem is not the lack of
      efficacy of available therapeutic measures, medications and procedures, but in
      insufficient implementation.

PMID- 27047274
TI  - FIRST BH COCHRANE SYMPOSIUM HELD.
AB  - The first BH Cochrane Symposium was held on 12 October 2015 in Sarajevo, Bosnia
      and Herzegovina (BH), organized by the Agency for Quality and Accreditation in
      Healthcare in Federation of BH (AKAZ) and Medical Faculty University of Sarajevo.
      A group of ten national and international experts presented the Cochrane
      organization and systematic reviews, as well as the IMPACT Observatory,
      development of guidelines in BH, and the role of AKAZ. Examples of the
      development and use of Cochrane reviews in evidence informed decision making in
      health as well as research integrity were presented and discussed. Major BH
      decision makers and interested professionals from all over BH participated in a
      symposium and its lively discussion, especially from the perspective of Cochrane
      and its activities in BH, and the collaboration with the Croatian Cochrane. It
      can be expected that this symposium will inspire further growth of participation
      and use of Cochrane in BH and increase the awareness of various aspects of
      evidence informed medicine and research integrity. 

PMID- 27047275
TI  - Focus on ECGs: A New Feature of the Texas Heart Institute Journal.

PMID- 27047276
TI  - Durability of the Starr-Edwards Heart Valve: Early Decisions Led to Successful
      Results.

PMID- 27047277
TI  - Cutting the Cost of Health Care: The Physician's Role.

PMID- 27047278
TI  - On the Life of Larry Graves: The First Child Ever to Have a Totally Implanted
      Pacemaker.

PMID- 27047279
TI  - Listening to Evelyn.

PMID- 27047280
TI  - The Mosaic Mitral Valve Bioprosthesis: A Long-Term Clinical and Hemodynamic
      Follow-Up.
AB  - We reviewed the cases of 100 patients (mean age, 73 +/- 10 yr; 64 men) who had
      mitral valve replacement with a Medtronic Mosaic porcine bioprosthesis from 1995
      through 2011. The mean New York Heart Association (NYHA) class was 3 +/- 0.7, and
      52 patients were in atrial fibrillation. Prosthetic sizes were chiefly 27 mm (50
      patients) and 29 mm (40 patients). Follow-up ended in December 2012 and is 97%
      complete, with a cumulative duration of 611 patient-years (mean duration, 6 +/-
      4.6 yr; maximum, 17.7 yr). The early mortality rate was 10% (6% in elective
      patients); late deaths occurred in 31 patients (5 valve-related). Actuarial
      survival rates at 5, 10, and 15 years were 74% +/- 5%, 50% +/- 6%, and 37% +/-
      8%. The mean NYHA class in survivors was 1.4 +/- 0.6 (P <0.0001). Thromboembolic
      episodes occurred in 4 patients, with an actuarial freedom at 15 years of 91% +/-
      5%. No cases of endocarditis were observed. Four patients needed reoperation, 2
      for structural failure, and 1 each for perivalvular leakage and valve thrombosis.
      Actuarial freedom from structural failure and from reoperation, respectively, was
      93% +/- 5% and 91% +/- 5% at 15 years. Echocardiographic follow-up in 24 patients
      with 27-mm prostheses showed a mean gradient of 5 +/- 1.7 mmHg and an effective
      orifice area of 1.57 +/- 0.3 cm(2); in 16 patients with 29-mm prostheses, the
      mean gradient was 4.5 +/- 1.9 mmHg, and the effective orifice area, 1.63 +/- 0.4
      cm(2). During nearly 17 years of follow-up, the Mosaic bioprosthesis has shown
      good overall clinical and hemodynamic performance after mitral valve replacement.

PMID- 27047281
TI  - Surgery for Aortic Root Abscess: A 15-Year Experience.
AB  - Aortic root abscess is the most severe sequela of infective endocarditis, and its
      surgical management is a complicated procedure because of the high risk of
      morbidity and death. Twenty-seven patients were included in this 15-year
      retrospective study: 21 (77.8%) with native- and 6 (22.2%) with prosthetic-valve
      endocarditis. The surgical reconstruction of the aortic root consisted of aortic
      valve replacement in 19 patients (70.4%) with (11) or without (8) a pericardial
      patch, or total aortic root replacement in 7 patients (25.9%); 5 of the 27
      (18.5%) underwent the modified Bentall procedure with the flanged conduit. Only
      one patient (3.7%) underwent subaortic pericardial patch reconstruction without
      valve replacement. A total of 7 patients (25.9%) underwent reoperation: 6 with
      prior valve surgery, and 1 with prior isolated sinus of Valsalva repair. The mean
      follow-up period was 6.8 +/- 3.7 years. There were 6 (22.2%) in-hospital deaths,
      3 (11.1%) of which were perioperative, among patients who underwent emergent
      surgery. Five patients (23.8%) died during follow-up, and the overall survival
      rates at 1, 5, and 10 years were 70.3% +/- 5.8%, 62.9% +/- 6.4%, and 59.2% +/-
      7.2%, respectively. Two of 21 patients (9.5%) underwent reoperation because of
      paravalvular leakage and early recurrence of infection during follow-up. After
      complete resection of the perianular abscess, replacement of the aortic root can
      be implemented for reconstruction of the aortic root, with or without left
      ventricular outflow tract injuries. Replacing the aortic root with a flanged
      composite graft might provide the best anatomic fit.

PMID- 27047282
TI  - Epicardial Adipose Tissue Thickness Is an Independent Predictor of Critical and
      Complex Coronary Artery Disease by Gensini and Syntax Scores.
AB  - Epicardial adipose tissue thickness is associated with the severity and extent of
      atherosclerotic coronary artery disease. We prospectively investigated whether
      epicardial adipose tissue thickness is related to coronary artery disease extent
      and complexity as denoted by Gensini and Syntax scores, and whether the thickness
      predicts critical disease. After performing coronary angiography in 183 patients
      who had angina or acute myocardial infarction, we divided them into 3 groups:
      normal coronary arteries, noncritical disease (>=1 coronary lesion with <70%
      stenosis), and critical disease (>=1 coronary lesion with <70% stenosis). We used
      transthoracic echocardiography to measure epicardial adipose tissue thickness,
      then calculated Gensini and Syntax scores by reviewing the angiograms. Mean
      thicknesses were 4.3 +/- 0.9, 5.2 +/- 1.5, and 7.5 +/- 1.9 mm in patients with
      normal coronary arteries, noncritical disease, and critical disease, respectively
      (P <0.001). At progressive thicknesses (<5, 5-7, and >7 mm), mean Gensini scores
      were 4.1 +/- 5.5, 19.8 +/- 15.6, and 64.9 +/- 32.4, and mean Syntax scores were
      4.7 +/- 5.9, 16.6 +/- 8.5, and 31.7 +/- 8.7, respectively (both P <0.001).
      Thickness had strong and positive correlations with both scores (Gensini, r
      =0.82, P <0.001; and Syntax, r =0.825, P <0.001). The cutoff thickness value to
      predict critical disease was 5.75 mm (area under the curve, 0.875; 95% confidence
      interval, 0.825-0.926; P <0.001). Epicardial adipose tissue thickness is
      independently related to coronary artery disease extent and complexity as denoted
      by Gensini and Syntax scores, and it predicts critical coronary artery disease.

PMID- 27047283
TI  - Predictors of Elevated Cardiac Enzyme Levels in Hospitalized Patients with Atrial
      Fibrillation and No Known Coronary Artery Disease.
AB  - We retrospectively studied the predictive capabilities of elevated cardiac enzyme
      levels in terms of the prognosis of patients who were hospitalized with atrial
      fibrillation and who had no known coronary artery disease. Among 321 patients
      with atrial fibrillation, 60 without known coronary artery disease had their
      cardiac enzyme concentrations measured during hospitalization and underwent
      stress testing or cardiac catheterization within 12 months before or after
      hospitalization. We then compared the clinical and electrocardiographic
      characteristics of the 20 patients who had elevated cardiac enzyme levels and the
      40 patients who had normal levels. Age, sex, and comorbidities did not differ
      between the groups. In the patients with elevated cardiac enzyme levels, the mean
      concentrations of troponin T and creatine kinase-MB isoenzymes were 0.08 +/- 0.08
      ng/mL and 6.49 +/- 4.94 ng/mL, respectively. In univariate analyses, only peak
      heart rate during atrial tachyarrhythmia was predictive of elevated enzyme levels
      (P <0.0001). Mean heart rate was higher in the elevated-level patients (146 +/-
      22 vs 117 +/- 29 beats/min; P=0.0007). Upon multivariate analysis, heart rate was
      the only independent predictor of elevated levels. Coronary artery disease was
      found in only 2 patients who had elevated levels and in one patient who had
      normal levels (P=0.26). Increased myocardial demand is probably why the
      presenting heart rate was predictive of elevated cardiac enzyme levels. Most
      patients with elevated enzyme levels did not have coronary artery disease, and
      none died of cardiac causes during the 6-month follow-up period. To validate our
      findings, larger studies are warranted.

PMID- 27047284
TI  - Alternative Surgical Approach to Repairing a Giant Sinus of Valsalva Aneurysm.
AB  - We report our method of surgically repairing an unruptured giant aneurysm of the
      right coronary sinus of Valsalva, a lesion that caused moderate aortic
      regurgitation but no symptoms in a 61-year-old woman. We excised the aneurysm,
      reconstructed the right sinus of Valsalva with use of a patch, performed
      mechanical aortic valve replacement directly through the excised aneurysm's
      cavity, and constructed a single bypass graft to the right coronary artery. The
      patient was discharged from the hospital after 5 days. Twelve months
      postoperatively, her clinical and echocardiographic results were normal, and she
      was doing well. To our knowledge, our surgical approach to this repair has not
      been described previously.

PMID- 27047285
TI  - Sinus of Valsalva Pseudoaneurysm as a Sequela to Infective Endocarditis.
AB  - Pseudoaneurysm is an uncommon sequela of infective endocarditis. We treated a 44
      year-old man who had an active case of group B streptococcal infective
      endocarditis of the aortic valve despite no evidence of valvular dysfunction or
      vegetation on his initial transesophageal echocardiogram. After completing 6
      weeks of intravenous antibiotic therapy, the patient developed a sinus of
      Valsalva pseudoaneurysm and severe aortic regurgitation caused by partial
      detachment of the left coronary cusp. We used a pericardial patch to close the
      pseudoaneurysm and repair the coronary cusp. This case shows the importance of
      routine clinical follow-up evaluation in infective endocarditis, even after
      completion of antibiotic therapy. Late sequelae associated with infective
      endocarditis or its therapy include recurrent infection, heart failure caused by
      valvular dysfunction (albeit delayed), and antibiotic toxicity such as
      aminoglycoside-induced nephropathy and vestibular toxicity.

PMID- 27047286
TI  - A Late Sequela of the David Procedure: Left Main Coronary Artery Compression and
      Myocardial Infarction due to Pseudoaneurysm Formation.
AB  - Valve-sparing root replacement (the David procedure) is a valuable alternative to
      conventional aortic root replacement with a composite graft, especially in
      patients whose aortic valve leaflets have not been altered. However,
      reintervention rates are higher than are those associated with composite graft
      implantation. In this report, we present the case of a patient who had undergone
      valve-sparing root replacement 2 years earlier and was admitted to our hospital
      with myocardial infarction and cardiogenic shock secondary to coronary ostial
      button dissection, aortic pseudoaneurysm formation, and severe left main coronary
      artery compression. To our knowledge, this case is exceedingly rare. Rather than
      attempt local reconstruction of the mouth of the pseudoaneurysm, we excised the
      lesion, the aortic valve, and the graft, and we successfully implanted a
      composite aortic graft with a mechanical aortic valve.

PMID- 27047287
TI  - Aortic Dissection Caused by Percutaneous Coronary Intervention: 2 New Case
      Reports and Detailed Analysis of 86 Previous Cases.
AB  - Aortic dissection, a rare sequela of percutaneous coronary intervention, can be
      fatal when it is not recognized and treated promptly. Treatment varies from
      conservative management to invasive aortic repair and revascularization. We
      report the cases of 2 patients whose aortic dissection was caused by percutaneous
      coronary intervention. In addition, we present detailed analyses of 86 previously
      reported cases. Aortic dissection was most often seen during intervention to the
      right coronary artery (in 76.7% of instances). The 2 most frequently reported
      causes were catheter trauma (in 54% of cases) and balloon inflation (in 23.8%).
      The overall mortality rate was 7.1%. We conclude that most patients can be
      treated conservatively or by means of stenting alone, with no need for surgical
      intervention.

PMID- 27047288
TI  - Takotsubo Cardiomyopathy in a 22-Year-Old Single-Ventricle Patient.
AB  - We report a highly unusual case of a 22-year-old woman with single-ventricle
      anatomy and a history of Fontan palliation who developed takotsubo
      cardiomyopathy. To our knowledge, takotsubo cardiomyopathy has not previously
      been described in a patient with single-ventricle anatomy, or more generally in
      any patient with congenital heart disease. The patient presented at our clinic
      for urgent examination after a 2-day history of chest pain that had begun upon
      the death of her dog. Invasive evaluation was refused by the patient; instead,
      she underwent electrocardiogram-gated coronary computed tomographic angiography,
      to rule out obstructive coronary disease. A physician who suspects takotsubo
      cardiomyopathy in a patient should look for new-onset chest pain and dyspnea
      coupled with these features: immediate onset of segmental akinesia in the
      midventricular or apical aspects of the heart, elevation of brain natriuretic
      peptide level 12 to 24 hours after onset of akinesia, elevation of troponin level
      24 to 48 hours after onset, and disappearance of the segmental akinesia a few
      days after onset.

PMID- 27047289
TI  - Progressive Left Ventricular Hypertrophy after Heart Transplantation: Insights
      and Mechanisms Suggested by Multimodal Images.
AB  - Immunosuppression is the typical measure to prevent rejection after heart
      transplantation. Although rejection is the usual cause of cardiac hypertrophy,
      numerous other factors warrant consideration. Calcineurin inhibitors rarely cause
      hypertrophic cardiomyopathy; the few relevant reports have described children
      after orthotopic kidney or liver transplantation. We present the case of a 73
      year-old woman, an asymptomatic orthotopic heart transplantation patient, in whom
      chronic immunosuppression with prednisone and cyclosporine apparently caused a
      phenotype of hypertrophic cardiomyopathy. The natural course of her midapical
      hypertrophy was revealed by single-photon-emission computed tomography, positron
      emission tomography, and 2-dimensional echocardiography. Clinicians and
      radiographers should be alert to progressive left ventricular hypertrophy and
      various perfusion patterns in heart transplantation patients even in the absence
      of underlying coronary artery disease. Toward this end, we recommend that
      advanced imaging methods be used to their fullest extent.

PMID- 27047290
TI  - Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2
      Human Immunodeficiency Virus-Seropositive Patients.
AB  - Few orthotopic heart transplantations have been performed in patients infected
      with the human immunodeficiency virus since the first such case was reported in
      2001. Since that time, advances in highly active antiretroviral therapy have
      resulted in potent and durable suppression of the causative human
      immunodeficiency virus-accompanied by robust immune reconstitution, reversal of
      previous immunodeficiency, a marked decrease in opportunistic and other
      infections, and near-normal long-term survival. Although human immunodeficiency
      virus infection is not an absolute contraindication, few centers in the United
      States and Canada have performed heart transplantations in this patient
      population; these patients have been de facto excluded from this procedure in
      North America. Re-evaluation of the reasons for excluding these patients from
      cardiac transplantation is warranted in light of such significant advances in
      antiretroviral therapy. This case report documents successful orthotopic heart
      transplantation in 2 patients infected with human immunodeficiency virus, and we
      describe their antiretroviral therapy and immunosuppressive management
      challenges. Both patients were doing well without sequelae 43 and 38 months after
      transplantation.

PMID- 27047291
TI  - Minimally Invasive Repair of Left Ventricular Pseudoaneurysm after Transapical
      Transcatheter Aortic Valve Replacement.
AB  - Transcatheter aortic valve replacement is becoming a routine procedure to treat
      severe symptomatic aortic stenosis. At most transcatheter aortic valve
      replacement centers, transapical access is a frequent alternative for use in
      patients whose ileofemoral access is inadequate. Transapical access is
      increasingly applied to a variety of other structural heart and aortic procedures
      as well. There is a caveat, however. When performed in elderly patients with
      friable myocardium, transapical access is associated with such serious sequelae
      as bleeding and left ventricular apical pseudoaneurysmal formation. Here, we
      describe the case of a 70-year-old woman who developed a left ventricular apical
      pseudoaneurysm 3 weeks after transapical transcatheter aortic valve replacement.
      Our successful repair took a minimally invasive left lateral approach that
      involved peripheral cardiopulmonary bypass cannulation, Foley catheter occlusion
      and primary defect closure, and BioGlue reinforcement.

PMID- 27047292
TI  - Cone Reconstruction of Atypical Ebstein Anomaly Associated with Right Ventricular
      Apical Hypoplasia.
AB  - Cone reconstruction for tricuspid valve repair has revolutionized the surgical
      treatment of Ebstein anomaly. We present the case of a 58-year-old woman with
      atypical Ebstein anomaly and right ventricular apical hypoplasia who was spared
      from palliative shunt physiology by our use of cone reconstruction. Compared with
      other techniques, cone reconstruction of the tricuspid valve more closely
      replicates normal valvular anatomy and function. This surgical procedure can be
      applied to many anatomic variations of Ebstein anomaly, as in our patient's
      apparently unique instance of atypical Ebstein anomaly with right ventricular
      apical hypoplasia.

PMID- 27047293
TI  - Angiosarcoma Causing Cardiac Constriction Late after Radiation Therapy for Breast
      Carcinoma.
AB  - Therapeutic radiotherapy rarely causes sarcoma, and this occurs years after
      completion of the intended treatment. In treating breast carcinoma, careful
      planning in the application of modern radiotherapeutic techniques usually can
      shield the heart and pericardium. We report a rare case of angiosarcoma of the
      pericardium, which presented in a 41-year-old woman as constrictive pericarditis
      8 years after irradiation for cancer of the left breast. To our knowledge, this
      is only the 2nd report of angiosarcoma of the pericardium after radiotherapy. 

PMID- 27047294
TI  - Primary Pulmonary Valve Leiomyosarcoma in a 35-Year-Old Woman.
AB  - Primary cardiac leiomyosarcomas are rare, with a high incidence of local
      recurrence. Herein, we report the case of a 35-year-old woman who was admitted
      with right ventricular failure and suspected pulmonary embolism. Upon
      echocardiography, we detected a mass in the pulmonary trunk that involved the
      pulmonary valve and led to valvular stenosis. The optimal protocol for treating
      these tumors is as yet unclear. Complete resection can rarely be achieved.
      However, palliative surgery is usually undertaken because many patients present
      with mechanical obstruction, such as significant pulmonary stenosis. 

PMID- 27047295
TI  - Implantable Cardioverter-Defibrillator Shock after Stenting Across the Device
      Leads.
AB  - A 45-year-old man with nonischemic cardiomyopathy and end-stage renal disease had
      lived uneventfully with a cardiac resynchronization therapy defibrillator (CRT-D)
      for 5 years. Less than a month before presenting at our institution, he had
      undergone stenting of his partially occluded subclavian vein, to relieve stenosis
      of the ipsilateral arteriovenous fistula that was used for his hemodialysis. The
      CRT-D subsequently discharged. Device interrogation revealed that electrical
      noise originating from leads damaged by the stent had caused the inappropriate
      shock and intermittent electrical discharges thereafter. The patient was highly
      traumatized by these events and insisted upon device removal, which deprived him
      of a potentially life-saving intervention. He later had a cardiac arrest that
      resulted in sustained profound hypoxic ischemic encephalopathy with minimal
      neurologic recovery: his family placed him in a long-term care facility on
      ventilator support, with a tracheostomy and feeding tube. This situation might
      have been avoided through collaboration between the interventional radiologist
      and the electrophysiologist. To our knowledge, this is the first report of a
      patient with nonischemic cardiomyopathy and end-stage renal disease who presented
      with inappropriate defibrillator discharge caused by lead damage secondary to
      stenting across the leads.

PMID- 27047296
TI  - Q Fever Endocarditis Presenting with Superior Mesenteric Artery Embolism and
      Renal Infarction.
AB  - Q fever is a zoonotic disease with a reservoir in mammals, birds, and ticks.
      Acute cases in human beings can be asymptomatic, or they can present with a flu
      like illness, pneumonia, or hepatitis. Approximately 5% of cases progress to
      chronic Q fever. Endocarditis, the most typical manifestation of chronic Q fever,
      is usually associated with small vegetations that occur in patients who have had
      prior valvular damage or who are immunocompromised. We present what we think is
      the first reported case of superior mesenteric artery embolism from Q fever
      endocarditis of the aortic valve, in a 39-year-old woman who needed surgical
      embolectomy and subsequent aortic valve replacement.

PMID- 27047297
TI  - Pacing on the T Wave: What Is the Cause?

PMID- 27047298
TI  - Starr-Edwards Caged-Ball Mitral Valve: Still Working after 41 Years.

PMID- 27047299
TI  - Ruptured Membrane of the Left Atrial Appendage.

PMID- 27047300
TI  - Multimodal Imaging of a Mitral Paravalvular Abscess.

PMID- 27047301
TI  - Methylene Blue Is a Guanylate Cyclase Inhibitor That Does Not Interfere with
      Nitric Oxide Synthesis.

PMID- 27047303
TI  - Taking a look at the calibration of a CCD detector with a fiber-optic taper.
AB  - At the Structural Biology Center beamline 19BM, located at the Advanced Photon
      Source, the operational characteristics of the equipment are routinely checked to
      ensure they are in proper working order. After performing a partial flat-field
      calibration for the ADSC Quantum 210r CCD detector, it was confirmed that the
      detector operates within specifications. However, as a secondary check it was
      decided to scan a single reflection across one-half of a detector module to
      validate the accuracy of the calibration. The intensities from this single
      reflection varied by more than 30% from the module center to the corner of the
      module. Redistribution of light within bent fibers of the fiber-optic taper was
      identified to be a source of this variation. The degree to which the diffraction
      intensities are corrected to account for characteristics of the fiber-optic
      tapers depends primarily upon the experimental strategy of data collection,
      approximations made by the data processing software during scaling, and crystal
      symmetry.

PMID- 27047304
TI  - Orientation relationship of eutectoid FeAl and FeAl2.
AB  - Fe-Al alloys in the aluminium range of 55-65 at.% exhibit a lamellar
      microstructure of B2-ordered FeAl and triclinic FeAl2, which is caused by a
      eutectoid decomposition of the high-temperature Fe5Al8 phase, the so-called ?
      phase. The orientation relationship of FeAl and FeAl2 has previously been studied
      by Bastin et al. [J. Cryst. Growth (1978 ?), 43, 745] and Hirata et al. [Philos.
      Mag. Lett. (2008 ?), 88, 491]. Since both results are based on different
      crystallographic data regarding FeAl2, the data are re-evaluated with respect to
      a recent re-determination of the FeAl2 phase provided by Chumak et al. [Acta
      Cryst. (2010 ?), C66, i87]. It is found that both orientation relationships match
      subsequent to a rotation operation of 180 degrees  about a <112> crystallographic
      axis of FeAl or by applying the inversion symmetry of the FeAl2 crystal structure
      as suggested by the Chumak data set. Experimental evidence for the validity of
      the previously determined orientation relationships was found in as-cast fully
      lamellar material (random texture) as well as directionally solidified material
      (~<110>FeAl || solidification direction) by means of orientation imaging
      microscopy and global texture measurements. In addition, a preferential interface
      between FeAl and FeAl2 was identified by means of trace analyses using cross
      sectioning with a focused ion beam. On the basis of these habit planes the
      orientation relationship between the two phases can be described by ([Formula:
      see text]01)FeAl || (114)[Formula: see text] and [111]FeAl || [1[Formula: see
      text]0][Formula: see text]. There is no evidence for twinning within FeAl
      lamellae or alternating orientations of FeAl lamellae. Based on the determined
      orientation and interface data, an atomistic model of the structure relationship
      of Fe5Al8, FeAl and FeAl2 in the vicinity of the eutectoid decomposition is
      derived. This model is analysed with respect to the strain which has to be
      accommodated at the interface of FeAl and FeAl2.

PMID- 27047305
TI  - Interlaced X-ray diffraction computed tomography.
AB  - An X-ray diffraction computed tomography data-collection strategy that allows,
      post experiment, a choice between temporal and spatial resolution is reported.
      This strategy enables time-resolved studies on comparatively short timescales, or
      alternatively allows for improved spatial resolution if the system under study,
      or components within it, appear to be unchanging. The application of the method
      for studying an Mn-Na-W/SiO2 fixed-bed reactor in situ is demonstrated.
      Additionally, the opportunities to improve the data-collection strategy further,
      enabling post-collection tuning between statistical, temporal and spatial
      resolutions, are discussed. In principle, the interlaced scanning approach can
      also be applied to other pencil-beam tomographic techniques, like X-ray
      fluorescence computed tomography, X-ray absorption fine structure computed
      tomography, pair distribution function computed tomography and tomographic
      scanning transmission X-ray microscopy.

PMID- 27047306
TI  - Expanding Lorentz and spectrum corrections to large volumes of reciprocal space
      for single-crystal time-of-flight neutron diffraction.
AB  - Evidence is mounting that potentially exploitable properties of technologically
      and chemically interesting crystalline materials are often attributable to local
      structure effects, which can be observed as modulated diffuse scattering (mDS)
      next to Bragg diffraction (BD). BD forms a regular sparse grid of intense
      discrete points in reciprocal space. Traditionally, the intensity of each Bragg
      peak is extracted by integration of each individual reflection first, followed by
      application of the required corrections. In contrast, mDS is weak and covers
      expansive volumes of reciprocal space close to, or between, Bragg reflections.
      For a representative measurement of the diffuse scattering, multiple sample
      orientations are generally required, where many points in reciprocal space are
      measured multiple times and the resulting data are combined. The common post
      integration data reduction method is not optimal with regard to counting
      statistics. A general and inclusive data processing method is needed. In this
      contribution, a comprehensive data analysis approach is introduced to correct and
      merge the full volume of scattering data in a single step, while correctly
      accounting for the statistical weight of the individual measurements. Development
      of this new approach required the exploration of a data treatment and correction
      protocol that includes the entire collected reciprocal space volume, using
      neutron time-of-flight or wavelength-resolved data collected at TOPAZ at the
      Spallation Neutron Source at Oak Ridge National Laboratory.

PMID- 27047307
TI  - Magnetic field-dependent spin structures of nanocrystalline holmium.
AB  - The results are reported of magnetic field-dependent neutron diffraction
      experiments on polycrystalline inert-gas condensed holmium with a nanometre
      crystallite size (D = 33 nm). At T = 50 K, no evidence is found for the existence
      of helifan(3/2) or helifan(2) structures for the nanocrystalline sample, in
      contrast with results reported in the literature for the single crystal. Instead,
      when the applied field H is increased, the helix pattern transforms
      progressively, most likely into a fan structure. It is the component of H which
      acts on the basal-plane spins of a given nanocrystallite that drives the
      disappearance of the helix; for nanocrystalline Ho, this field is about 1.3 T,
      and it is related to a characteristic kink in the virgin magnetization curve. For
      a coarse-grained Ho sample, concomitant with the destruction of the helix phase,
      the emergence of an unusual angular anisotropy (streak pattern) and the
      appearance of novel spin structures are observed.

PMID- 27047308
TI  - Multigrain indexing of unknown multiphase materials.
AB  - A multigrain indexing algorithm for use with samples comprising an arbitrary
      number of known or unknown phases is presented. No a priori crystallographic
      knowledge is required. The algorithm applies to data acquired with a
      monochromatic beam and a conventional two-dimensional detector for diffraction.
      Initially, candidate grains are found by searching for crystallographic planes,
      using a Dirac comb convoluted with a box function as a filter. Next, candidate
      grains are validated and the unit cell is optimized. The algorithm is validated
      by simulations. Simulations of 500 cementite grains and ~100 reflections per
      grain resulted in 99.2% of all grains being indexed correctly and 99.5% of the
      reflections becoming associated with the right grain. Simulations with 200 grains
      associated with four mineral phases and 50-700 reflections per grain resulted in
      99.9% of all grains being indexed correctly and 99.9% of the reflections becoming
      associated with the right grain. The main limitation is in terms of overlap of
      diffraction spots and computing time. Potential areas of use include three
      dimensional grain mapping, structural solution and refinement studies of complex
      samples, and studies of dilute phases.

PMID- 27047309
TI  - The Stanford Automated Mounter: pushing the limits of sample exchange at the SSRL
      macromolecular crystallography beamlines.
AB  - The Stanford Automated Mounter System, a system for mounting and dismounting cryo
      cooled crystals, has been upgraded to increase the throughput of samples on the
      macromolecular crystallography beamlines at the Stanford Synchrotron Radiation
      Lightsource. This upgrade speeds up robot maneuvers, reduces the heating/drying
      cycles, pre-fetches samples and adds an air-knife to remove frost from the
      gripper arms. Sample pin exchange during automated crystal quality screening now
      takes about 25 s, five times faster than before this upgrade.

PMID- 27047310
TI  - Facilitating model reconstruction for single-particle scattering using small
      angle X-ray scattering methods.
AB  - X-ray free-electron lasers generate intense femtosecond X-ray pulses, so that
      high-resolution structure determination becomes feasible from noncrystalline
      samples, such as single particles or single molecules. At the moment, the
      orientation of sample particles cannot be precisely controlled, and consequently
      the unknown orientation needs to be recovered using computational algorithms.
      This delays the model reconstruction until all the scattering patterns have been
      re-oriented, which often entails a long elapse of time and until the completion
      of the experiment. The scattering patterns from single particles or multiple
      particles can be summed to form a virtual powder diffraction pattern, and the low
      resolution region, corresponding to the small-angle X-ray scattering (SAXS)
      regime, can be analysed using existing SAXS methods. This work presents a
      pipeline that converts single-particle data sets into SAXS data, from which real
      time model reconstruction is achieved using the model retrieval approach
      implemented in the software package SASTBX [Liu, Hexemer & Zwart (2012). J. Appl.
      Cryst.45, 587-593]. To illustrate the applications, two case studies are
      presented with real experimental data sets collected at the Linac Coherent Light
      Source.

PMID- 27047311
TI  - Recent developments in CrystFEL.
AB  - CrystFEL is a suite of programs for processing data from 'serial crystallography'
      experiments, which are usually performed using X-ray free-electron lasers (FELs)
      but also increasingly with other X-ray sources. The CrystFEL software suite has
      been under development since 2009, just before the first hard FEL experiments
      were performed, and has been significantly updated and improved since then. This
      article describes the most important improvements which have been made to
      CrystFEL since the first release version. These changes include the addition of
      new programs to the suite, the ability to resolve 'indexing ambiguities' and
      several ways to improve the quality of the integrated data by more accurately
      modelling the underlying diffraction physics.

PMID- 27047312
TI  - Adrenal involvement in histoplasmosis.
AB  - Histoplasmosis infection is endemic in Asia and disseminated histoplasmosis (DH)
      is one form of its presentation (Benevides et al., 2007[1]). DH commonly affects
      both adrenal glands. We describe a case of disseminated histoplasmosis
      complicated with hypercalcaemia in a 75-year-old immunosuppressed patient who
      presented with bilateral adrenal masses. The fine needle aspiration cytology of
      the adrenal mass was positive for Histoplasma capsulatum. 

PMID- 27047313
TI  - Seasonal variability of Chelidonium majus L. secondary metabolites content and
      antioxidant activity.
AB  - The aim of this study is to investigate the total phenolic content, concentration
      of flavonoids and antioxidant activity in extracts of the plant Chelidonium majus
      L. during different phenological stages (stage of rosette, the initial flowering
      stage, the stage of fully formed flowers and stage of fruits formation). Five
      different extracts of the whole plant, for each phase, were obtained by
      extraction with water, methanol, acetone, ethyl acetate and petroleum ether. The
      concentration of total phenolic content was determined using the Folin
      Ciocalteu's reagent and obtained values were the highest in the rosette stage
      (60.96 mg GA/g). The concentration of flavonoids was the highest in the initial
      stage of flowering (291.58 mg RU/g). The antioxidant activity was determined in
      vitro using DPPH reagent. The highest antioxidant activity was expressed in the
      rosette stage (50.72 mg/ml). Based on the obtained results it can be concluded
      that the concentrations of secondary metabolites in Ch. majus depend on the
      phenological stage of the plant. 

PMID- 27047315
TI  - Persimmon (Diospyros kaki) fruit: hidden phytochemicals and health claims.
AB  - Currently, nutrition and health linkages focused on emerging strategy of diet
      based regimen to combat various physiological threats including cardiovascular
      disorders, oxidative stress, diabetes mellitus, etc. In this context, consumption
      of fruits and vegetables is gaining considerable importance as safeguard to
      maintain human health. Likewise, their phytochemicals and bioactive molecules are
      also becoming popular as promising demulcent against various ailments. The
      current review is an effort to sum up information regarding persimmon fruit with
      special reference to its phytochemistry and associated health claims.
      Accordingly, the role of its certain bioactive molecules like proanthocyanidin,
      carotenoids, tannins, flavonoids, anthocyanidin, catechin, etc. is highlighted.
      Owing to rich phytochemistry, persimmon and its products are considered effective
      in mitigating oxidative damage induced by reactive oxygen species (ROS). The
      antioxidant potential is too responsible for anti-malignant and anti-melanogenic
      perspectives of persimmon functional ingredients. Additionally, they are
      effectual in soothing lifestyle related disparities e.g. cardiovascular disorders
      and diabetes mellitus. There are proven facts that pharmacological application of
      persimmon or its functional ingredients like proanthocyanidin may helps against
      hyperlipidemia and hyperglycemia. Nevertheless, astringent taste and
      diospyrobezoars formation are creating lacuna to prop up its vitality. In toto,
      persimmon and its components hold potential as one of effective modules in diet
      based therapy; however, integrated research and meta-analysis are still required
      to enhance meticulousness. 

PMID- 27047314
TI  - Data- and knowledge-based modeling of gene regulatory networks: an update.
AB  - Gene regulatory network inference is a systems biology approach which predicts
      interactions between genes with the help of high-throughput data. In this review,
      we present current and updated network inference methods focusing on novel
      techniques for data acquisition, network inference assessment, network inference
      for interacting species and the integration of prior knowledge. After the advance
      of Next-Generation-Sequencing of cDNAs derived from RNA samples (RNA-Seq) we
      discuss in detail its application to network inference. Furthermore, we present
      progress for large-scale or even full-genomic network inference as well as for
      small-scale condensed network inference and review advances in the evaluation of
      network inference methods by crowdsourcing. Finally, we reflect the current
      availability of data and prior knowledge sources and give an outlook for the
      inference of gene regulatory networks that reflect interacting species, in
      particular pathogen-host interactions. 

PMID- 27047317
TI  - An update on the potential health benefits of carotenes.

PMID- 27047318
TI  - Chemically synthesized CdSe quantum dots inhibit growth of human lung carcinoma
      cells via ROS generation.
AB  - Quantum dots (QDs), semiconducting materials have potential applications in the
      field of electronic and biomedical applications including cancer therapy. In
      present study, cadmium selenide (CdSe) QDs were synthesized by chemical method.
      Octadecene was used as non-coordinating solvent which facilitated the formation
      of colloidal solutions of nanoparticles. CdSe QDs were characterized by UV-vis
      spectrometer and transmission electron microscope (TEM). The size measured by TEM
      was varied between 2-5 nm depending upon temperature. The cytotoxic activity of
      QDs was monitored by MTT assay, nuclear condensation, ROS activity and DNA
      fragmentation assay on human lung epithelial A549 cell line. Cells were treated
      with different concentrations of varying size of CdSe QDs for 24 h. CdSe QDs
      induced significant (p < 0.05) dose dependent cytotoxicity and this was
      comparable to the sizes of particles. Smaller particles were more cytotoxic to
      the large particles. Fluorescence microscopic analysis revealed that QDs induced
      oxidative stress generating significant ROS level and consequently, induced
      nuclear condensation and DNA fragmentation. Study suggested the cytotoxicity of
      CdSe QDs via ROS generation and DNA fragmentation depending upon particles size. 

PMID- 27047316
TI  - Experimental procedures to identify and validate specific mRNA targets of miRNAs.
AB  - Functionally matured microRNAs (miRNAs) are small single-stranded non-coding RNA
      molecules which are emerging as important post-transcriptional regulators of gene
      expression and consequently are central players in many physiological and
      pathological processes. Since the biological roles of individual miRNAs will be
      dictated by the mRNAs that they regulate, the identification and validation of
      miRNA/mRNA target interactions is critical for our understanding of the
      regulatory networks governing biological processes. We promulgate the combined
      use of prediction algorithms, the examination of curated databases of
      experimentally supported miRNA/mRNA interactions, manual sequence inspection of
      cataloged miRNA binding sites in specific target mRNAs, and review of the
      published literature as a reliable practice for identifying and prioritizing
      biologically important miRNA/mRNA target pairs. Once a preferred miRNA/mRNA
      target pair has been selected, we propose that the authenticity of a functional
      miRNA/mRNA target pair be validated by fulfilling four well-defined experimental
      criteria. This review summarizes our current knowledge of miRNA biology,
      miRNA/mRNA target prediction algorithms, validated miRNA/mRNA target data bases,
      and outlines several experimental methods by which miRNA/mRNA targets can be
      authenticated. In addition, a case study of human endoglin is presented as an
      example of the utilization of these methodologies. 

PMID- 27047319
TI  - The effect of cold application and lavender oil inhalation in cardiac surgery
      patients undergoing chest tube removal.
AB  - Post-surgical chest tube removal (CTR) is associated with a significant pain and
      discomfort for patients. Current treatment strategies for reducing CTR-associated
      pain and anxiety are limited and partially efficacious. To determine the effects
      of cold application, inhalation of lavender essential oil, and their combination
      on pain and anxiety during CTR was investigated. This randomized controlled open
      label trial was conducted with 80 patients in the cardiac surgery intensive care
      unit who had a chest tube for duration of at least 24 hours after coronary artery
      bypass grafting (CABG). Patients were randomized (n=20 in each group) to receive
      cold application, aromatherapy with lavender oil, cold application in combination
      with lavender oil inhalation, or none of the above interventions (control group).
      The intensity and quality of pain and anxiety were evaluated using the visual
      analogue scale, short form and modified-McGill pain questionnaire (SFM-MPQ) and
      the Spielberger situational anxiety level inventory (STAII) scale, respectively.
      Patients in all treatment groups had significantly lower pain intensity and
      anxiety compared with the control group immediately, 5, 10 and 15 min after CTR.
      There was no statistically significant difference in the SFM-MPQ total scores
      between the intervention groups. With respect to anxiety score, there was a
      significantly reduced anxiety level immediately after CTR in the aromatherapy and
      cold-aromatherapy combination groups versus the cold application group. The
      present results suggested the efficacy of cold application and aromatherapy with
      lavender oil in reducing pain and anxiety associated with post-CABG CTR. 

PMID- 27047320
TI  - Phytochemical evaluation, antioxidant assay, antibacterial activity and
      determination of cell viability (J774 and THP1 alpha cell lines) of P. sylvestris
      leaf crude and methanol purified fractions.
AB  - Phoenix sylvestris (Arecaceae family) known as Indian Date Palm has been
      identified as a component of traditional medicine against various ailments. The
      present study was focused on phytochemical screening of crude hexane,
      dichloromethane and methanol leaf extracts. The crude extracts showed the
      presence of alkaloids, flavonoids, and phenols in the plant leaves. In the study
      methanol extract was found most potent, so this extract was further fractionated
      by column chromatography and 9 methanol purified fractions (MPFs) were isolated.
      Most potential MPF8 (20:80 chloroform: methanol ratio fraction) significantly
      enhanced free radicals and antibacterial activity. The best MIC (Minimum
      inhibitory concentration) of MPF8 was investigated against M. luteus and E. coli
      at 1 mg/ml concentration. However, against other bacteria the MIC ranged from 1
      mg/ml to 3 mg/ml. The GC-MS analysis showed the presence of many biologically
      active compounds such as alcohols, flavonoids, aromatic compounds, aldehydes,
      terpenoids fatty acid methyl esters, and phenolics. Pentadecanoic acid occupied
      maximum (52 %) area in GC-MS profiling. MPF8 was assayed for in-vitro
      cytotoxicity by MTT assay which confirms its less cytotoxicity at lower
      concentration and also significant ROS determination against J774 and THP1 cell
      lines after 2 and 4 hours. 

PMID- 27047321
TI  - P-glycoprotein transporter in drug development.

PMID- 27047322
TI  - Plant polyphenols can protect VEGF-induced vascular leakage?

PMID- 27047323
TI  - Highlight report: Cardiotoxicity screening.

PMID- 27047324
TI  - Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability
      Affects Stopping Behavior.
AB  - Inhibitory control, the ability to stop or modify preplanned actions under
      changing task conditions, is an important component of cognitive functions. Two
      lines of models of inhibitory control have previously been proposed for human
      response in the classical stop-signal task, in which subjects must inhibit a
      default go response upon presentation of an infrequent stop signal: (1) the race
      model, which posits two independent go and stop processes that race to determine
      the behavioral outcome, go or stop; and (2) an optimal decision-making model,
      which posits that observers decides whether and when to go based on continually
      (Bayesian) updated information about both the go and stop stimuli. In this work,
      we probe the relationship between go and stop processing by explicitly
      manipulating the discrimination difficulty of the go stimulus. While the race
      model assumes the go and stop processes are independent, and therefore go
      stimulus discriminability should not affect the stop stimulus processing, we
      simulate the optimal model to show that it predicts harder go discrimination
      should result in longer go reaction time (RT), lower stop error rate, as well as
      faster stop-signal RT. We then present novel behavioral data that validate these
      model predictions. The results thus favor a fundamentally inseparable account of
      go and stop processing, in a manner consistent with the optimal model, and
      contradicting the independence assumption of the race model. More broadly, our
      findings contribute to the growing evidence that the computations underlying
      inhibitory control are systematically modulated by cognitive influences in a
      Bayes-optimal manner, thus opening new avenues for interpreting neural responses
      underlying inhibitory control. 

PMID- 27047326
TI  - Bayesian Estimation and Inference Using Stochastic Electronics.
AB  - In this paper, we present the implementation of two types of Bayesian inference
      problems to demonstrate the potential of building probabilistic algorithms in
      hardware using single set of building blocks with the ability to perform these
      computations in real time. The first implementation, referred to as the BEAST
      (Bayesian Estimation and Stochastic Tracker), demonstrates a simple problem where
      an observer uses an underlying Hidden Markov Model (HMM) to track a target in one
      dimension. In this implementation, sensors make noisy observations of the target
      position at discrete time steps. The tracker learns the transition model for
      target movement, and the observation model for the noisy sensors, and uses these
      to estimate the target position by solving the Bayesian recursive equation
      online. We show the tracking performance of the system and demonstrate how it can
      learn the observation model, the transition model, and the external distractor
      (noise) probability interfering with the observations. In the second
      implementation, referred to as the Bayesian INference in DAG (BIND), we show how
      inference can be performed in a Directed Acyclic Graph (DAG) using stochastic
      circuits. We show how these building blocks can be easily implemented using
      simple digital logic gates. An advantage of the stochastic electronic
      implementation is that it is robust to certain types of noise, which may become
      an issue in integrated circuit (IC) technology with feature sizes in the order of
      tens of nanometers due to their low noise margin, the effect of high-energy
      cosmic rays and the low supply voltage. In our framework, the flipping of random
      individual bits would not affect the system performance because information is
      encoded in a bit stream. 

PMID- 27047325
TI  - Hemodynamic Response to Interictal Epileptiform Discharges Addressed by
      Personalized EEG-fNIRS Recordings.
AB  - OBJECTIVE: We aimed at studying the hemodynamic response (HR) to Interictal
      Epileptic Discharges (IEDs) using patient-specific and prolonged simultaneous
      ElectroEncephaloGraphy (EEG) and functional Near InfraRed Spectroscopy (fNIRS)
      recordings. METHODS: The epileptic generator was localized using
      Magnetoencephalography source imaging. fNIRS montage was tailored for each
      patient, using an algorithm to optimize the sensitivity to the epileptic
      generator. Optodes were glued using collodion to achieve prolonged acquisition
      with high quality signal. fNIRS data analysis was handled with no a priori
      constraint on HR time course, averaging fNIRS signals to similar IEDs. Cluster
      permutation analysis was performed on 3D reconstructed fNIRS data to identify
      significant spatio-temporal HR clusters. Standard (GLM with fixed HRF) and
      cluster-permutation EEG-fMRI analyses were performed for comparison purposes.
      RESULTS: fNIRS detected HR to IEDs for 8/9 patients. It mainly consisted oxy
      hemoglobin increases (seven patients), followed by oxy-hemoglobin decreases (six
      patients). HR was lateralized in six patients and lasted from 8.5 to 30 s.
      Standard EEG-fMRI analysis detected an HR in 4/9 patients (4/9 without enough
      IEDs, 1/9 unreliable result). The cluster-permutation EEG-fMRI analysis
      restricted to the region investigated by fNIRS showed additional strong and non
      canonical BOLD responses starting earlier than the IEDs and lasting up to 30 s.
      CONCLUSIONS: (i) EEG-fNIRS is suitable to detect the HR to IEDs and can
      outperform EEG-fMRI because of prolonged recordings and greater chance to detect
      IEDs; (ii) cluster-permutation analysis unveils additional HR features
      underestimated when imposing a canonical HR function (iii) the HR is often
      bilateral and lasts up to 30 s.

PMID- 27047327
TI  - Nanoparticles: A Challenging Vehicle for Neural Stimulation.
AB  - Neurostimulation represents a powerful and well-established tool for the
      treatment of several diseases affecting the central nervous system. Although,
      effective in reducing the symptoms or the progression of brain disorders, the
      poor accessibility of the deepest areas of the brain currently hampers the
      possibility of a more specific and controlled therapeutic stimulation, depending
      on invasive surgical approaches and long-term stability, and biocompatibility
      issues. The massive research of the last decades on nanomaterials and nanoscale
      devices favored the development of new tools to address the limitations of the
      available neurostimulation approaches. This mini-review focuses on the employment
      of nanoparticles for the modulation of the electrophysiological activity of
      neuronal networks and the related transduction mechanisms underlying the
      nanostructure-neuron interfaces. 

PMID- 27047328
TI  - Believer-Skeptic Meets Actor-Critic: Rethinking the Role of Basal Ganglia
      Pathways during Decision-Making and Reinforcement Learning.
AB  - The flexibility of behavioral control is a testament to the brain's capacity for
      dynamically resolving uncertainty during goal-directed actions. This ability to
      select actions and learn from immediate feedback is driven by the dynamics of
      basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with
      the traditional view that these pathways act as independent levers for
      facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor
      output, suggesting instead that they engage in a dynamic competition during
      action decisions that computationally captures action uncertainty. Here we
      discuss the utility of encoding action uncertainty as a dynamic competition
      between opposing control pathways and provide evidence that this simple mechanism
      may have powerful implications for bridging neurocomputational theories of
      decision making and reinforcement learning. 

PMID- 27047329
TI  - Mosaic Subventricular Origins of Forebrain Oligodendrogenesis.
AB  - In the perinatal as well as the adult CNS, the subventricular zone (SVZ) of the
      forebrain is the largest and most active source of neural stem cells (NSCs) that
      generates neurons and oligodendrocytes (OLs), the myelin forming cells of the
      CNS. Recent advances in the field are beginning to shed light regarding SVZ
      heterogeneity, with the existence of spatially segregated microdomains that are
      intrinsically biased to generate phenotypically distinct neuronal populations.
      Although most research has focused on this regionalization in the context of
      neurogenesis, newer findings underline that this also applies for the genesis of
      OLs under the control of specific patterning molecules. In this mini review, we
      discuss the origins as well as the mechanisms that induce and maintain SVZ
      regionalization. These come in the flavor of specific signaling ligands and
      subsequent initiation of transcriptional networks that provide a basis for
      subdividing the SVZ into distinct lineage-specific microdomains. We further
      emphasize canonical Wnts and FGF2 as essential signaling pathways for the
      regional genesis of OL progenitors from NSCs of the dorsal SVZ. This aspect of
      NSC biology, which has so far received little attention, may unveil new avenues
      for appropriately recruiting NSCs in demyelinating diseases. 

PMID- 27047330
TI  - Discerning Neurogenic vs. Non-Neurogenic Postnatal Lateral Ventricular Astrocytes
      via Activity-Dependent Input.
AB  - Throughout development, neural stem cells (NSCs) give rise to differentiated
      neurons, astrocytes, and oligodendrocytes which together modulate perception,
      memory, and behavior in the adult nervous system. To understand how NSCs
      contribute to postnatal/adult brain remodeling and repair after injury, the
      lateral ventricular (LV) neurogenic niche in the rodent postnatal brain serves as
      an excellent model system. It is a specialized area containing self-renewing
      GFAP(+) astrocytes functioning as NSCs generating new neurons throughout life. In
      addition to this now well-studied regenerative process, the LV niche also
      generates differentiated astrocytes, playing an important role for glial scar
      formation after cortical injury. While LV NSCs can be clearly distinguished from
      their neuroblast and oligodendrocyte progeny via molecular markers, the
      astrocytic identity of NSCs has complicated their distinction from terminally
      differentiated astrocytes in the niche. Our current models of postnatal/adult LV
      neurogenesis do not take into account local astrogenesis, or the possibility that
      cellular markers may be similar between non-dividing GFAP(+) NSCs and their
      differentiated astrocyte daughters. Postnatal LV neurogenesis is regulated by NSC
      intrinsic mechanisms interacting with extracellular/niche-driven cues. It is
      generally believed that these local effects are responsible for sustaining
      neurogenesis, though behavioral paradigms and disease states have suggested
      possibilities for neural circuit-level modulation. With recent experimental
      findings that neuronal stimulation can directly evoke responses in LV NSCs, it is
      possible that this exciting property will add a new dimension to identifying
      postnatal/adult NSCs. Here, we put forth a notion that neural circuit-level input
      can be a distinct characteristic defining postnatal/adult NSCs from non
      neurogenic astroglia. 

PMID- 27047331
TI  - Estrogenic Effects of Several BPA Analogs in the Developing Zebrafish Brain.
AB  - Important set of studies have demonstrated the endocrine disrupting activity of
      Bisphenol A (BPA). The present work aimed at defining estrogenic-like activity of
      several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4- or 7
      day post-fertilization (dpf) zebrafish larva as an in vivo model. We measured the
      induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B),
      expressed in the brain, using three different in situ/in vivo strategies: (1)
      Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva
      brains exposed to bisphenols; (2) Detection and distribution of cyp19a1b
      transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus);
      and (3) Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP
      transgenic zebrafish (EASZY assay) at 4-dpf larval stage. These three different
      experimental approaches demonstrated that BPS, BPF, or BPAF exposure, similarly
      to BPA, significantly activates the expression of the estrogenic marker in the
      brain of developing zebrafish. In vitro experiments using both reporter gene
      assay in a glial cell context and competitive ligand binding assays strongly
      suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish
      estrogen nuclear receptor alpha (zfERalpha). Importantly, and in contrast to
      other tested bisphenol A analogs, the bisphenol AP (BPAP) did not show estrogenic
      activity in our model. 

PMID- 27047332
TI  - Self-Regulation of Blood Oxygenation Level Dependent Response: Primary Effect or
      Epiphenomenon?

PMID- 27047333
TI  - Inflammation and Elevation of Interleukin-12p40 in Patients with Schizophrenia.
AB  - Schizophrenia is a serious mental illness with chronic symptoms and significant
      impairment in psychosocial functioning, which suggests that it likely has
      neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory
      cytokines are well-known etiological contributors for psychiatric disorders,
      including schizophrenia. Although, the role of inflammation in schizophrenia is
      becoming evident, the number of studies in this area is relatively scarce,
      especially in Lebanon, and increased procedural thoroughness is needed. Cytokines
      play a key role in the activation of the immune system and strongly influence
      neurotransmission. Previous investigation of plasma levels showed dysregulation
      of interleukin (IL)-12. However, genotypical variations of this interleukin have
      not been investigated for patients with schizophrenia yet. Thus, in this paper,
      we aimed to compute and assess IL-12p40 levels in the sera of individuals with
      schizophrenia from different provinces in Lebanon and compare it to controls.
      Healthy subjects comprised 60 individuals with a male/female (M/F) ratio of
      31/29, whereas patients with schizophrenia consisted of 63 subjects with an M/F
      ratio of 30/33. The mean age for healthy controls was 30 years, whereas that for
      patients with schizophrenia was 35 years. A standardized enzyme-linked
      immunosorbent assay (ELISA) technique was used to measure the concentration of IL
      12p40 in all collected sera (n = 123). The mean IL-12p40 levels in patients with
      schizophrenia were significantly higher than in healthy controls (p = 0.002).
      Healthy females had a significantly higher concentration of IL-12p40 than healthy
      males (p = 0.009). Female patients with schizophrenia had significantly higher
      concentrations of IL-12p40 than their male counterparts (p < 0.001), healthy
      females (p = 0.018), and healthy males (p < 0.001), respectively. Male patients
      with schizophrenia had significantly higher concentrations of IL-12p40 than
      healthy males (p = 0.023). The study's results suggest that IL-12p40 has a
      putative role as a potential marker in schizophrenia and that its elevation may
      participate in its pathogenesis. IL-12p40 may be included in a panel to be
      evaluated in the sera of patients with schizophrenia and an appreciation of its
      independent function is important for improving our understanding of both
      protective and pathogenic immune responses. Future research should aim to assess
      this interleukin and understand its role in other mental illnesses that share a
      similar etiology to schizophrenia. 

PMID- 27047334
TI  - MicroRNAs Are Involved in the Development of Morphine-Induced Analgesic Tolerance
      and Regulate Functionally Relevant Changes in Serpini1.
AB  - Long-term opioid treatment results in reduced therapeutic efficacy and in turn
      leads to an increase in the dose required to produce equivalent pain relief and
      alleviate break-through or insurmountable pain. Altered gene expression is a
      likely means for inducing long-term neuroadaptations responsible for tolerance.
      Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of
      gene expression changes occurring in canonical pathways involved in
      neuroplasticity, and uncovered miRNA processing as a potential mechanism. In
      particular, the mRNA coding the protein responsible for processing miRNAs,
      Dicer1, was positively correlated with the development of analgesic tolerance.
      The purpose of the present study was to test the hypothesis that miRNAs play a
      significant role in the development of analgesic tolerance as measured by thermal
      nociception. Dicer1 knockdown, miRNA profiling, bioinformatics, and confirmation
      of high value targets were used to test the proposition. Regionally targeted
      Dicer1 knockdown (via shRNA) had the anticipated consequence of eliminating the
      development of tolerance in C57BL/6J (B6) mice, thus supporting the involvement
      of miRNAs in the development of tolerance. MiRNA expression profiling identified
      a core set of chronic morphine-regulated miRNAs (miR's 27a, 9, 483, 505, 146b,
      202). Bioinformatics approaches were implemented to identify and prioritize their
      predicted target mRNAs. We focused our attention on miR27a and its predicted
      target serpin peptidase inhibitor clade I (Serpini1) mRNA, a transcript known to
      be intricately involved in dendritic spine density regulation in a manner
      consistent with chronic morphine's consequences and previously found to be
      correlated with the development of analgesic tolerance. In vitro reporter assay
      confirmed the targeting of the Serpini1 3'-untranslated region by miR27a.
      Interestingly miR27a was found to positively regulate Serpini1 mRNA and protein
      levels in multiple neuronal cell lines. Lastly, Serpini1 knockout mice developed
      analgesic tolerance at a slower rate than wild-type mice thus confirming a role
      for the protein in analgesic tolerance. Overall, these results provide evidence
      to support a specific role for miR27a and Serpini1 in the behavioral response to
      chronic opioid administration (COA) and suggest that miRNA expression and mRNA
      targeting may underlie the neuroadaptations that mediate tolerance to the
      analgesic effects of morphine. 

PMID- 27047335
TI  - Editorial: Glial Cells: Managers of Neuro-Immunity.

PMID- 27047336
TI  - Involvement of HCN Channel in Muscarinic Inhibitory Action on Tonic Firing of
      Dorsolateral Striatal Cholinergic Interneurons.
AB  - The striatum is the most prominent nucleus in the basal ganglia and plays an
      important role in motor movement regulation. The cholinergic interneurons (ChIs)
      in striatum are involved in the motion regulation by releasing acetylcholine
      (ACh) and modulating the output of striatal projection neurons. Here, we report
      that muscarinic ACh receptor (M receptor) agonists, ACh and Oxotremorine (OXO-M),
      decreased the firing frequency of ChIs by blocking the hyperpolarization
      activated cyclic nucleotide-gated (HCN) channels. Scopolamine (SCO), a
      nonselective antagonist of M receptors, abolished the inhibition. OXO-M exerted
      its function by activating the Gi/o cAMP signaling cascade. The single-cell
      reverse transcription polymerase chain reaction (scRT-PCR) revealed that all the
      five subtypes of M receptors and four subtypes of HCN channels were expressed on
      ChIs. Among them, M2 receptors and HCN2 channels were the most dominant ones and
      expressed in every single studied cholinergic interneuron (ChI).Our results
      suggest that ACh regulates not only the output of striatal projection neurons,
      but also the firing activity of ChIs themselves by activating presynaptic M
      receptors in the dorsal striatum. The activation of M2 receptors and blockage of
      HCN2 channels may play an important role in ACh inhibition on the excitability of
      ChIs. This finding adds a new G-protein coupled receptor mediated regulation on
      ChIs and provides a cellular mechanism for control of cholinergic activity and
      ACh release in the dorsal striatum. 

PMID- 27047337
TI  - Sirtuin-3 Is Expressed by Enteric Neurons but It Does not Play a Major Role in
      Their Regulation of Oxidative Stress.
AB  - Gut inflammation contributes to the development of gut motility disorders in part
      by disrupting the function and survival of enteric neurons through mechanisms
      that involve oxidative stress. How enteric neurons regulate oxidative stress is
      still poorly understood. Importantly, how neuron autonomous antioxidant
      mechanisms contribute to the susceptibility of enteric neurons to oxidative
      stress in disease is not known. Here, we discover that sirtuin-3 (Sirt3), a key
      regulator of oxidative stress and mitochondrial metabolism, is expressed by
      neurons in the enteric nervous system (ENS) of the mouse colon. Given the
      important role of Sirt3 in the regulation of neuronal oxidative stress in the
      central nervous system (CNS), we hypothesized that Sirt3 plays an important role
      in the cell autonomous regulation of oxidative stress by enteric neurons and that
      a loss of Sirt3 increases neuronal vulnerability during intestinal inflammation.
      We tested our hypothesis using a combination of traditional immunohistochemistry,
      oxidative stress measurements and in vivo and ex vivo measures of GI motility in
      healthy and inflamed wild-type (wt) and Sirt3 null (Sirt3 (-/-)) mice. Our
      results show that Sirt3 is widely expressed by neurons throughout the myenteric
      plexus of the mouse colon. However, the deletion of Sirt3 had surprisingly little
      effect on gut function and susceptibility to inflammation. Likewise, neither the
      genetic ablation of Sirt3 nor the inhibition of Sirt3 with antagonists had a
      significant effect on neuronal oxidative stress. Therefore, we conclude that
      Sirt3 contributes very little to the overall regulation of neuronal oxidative
      stress in the ENS. The functional relevance of Sirt3 in enteric neurons is still
      unclear but our data show that it is an unlikely candidate to explain neuronal
      vulnerability to oxidative stress during inflammation. 

PMID- 27047338
TI  - Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic
      Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.
AB  - Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased
      neuronal excitability and synaptic activity in the hippocampus. We have
      previously shown that synaptic activity in hippocampi of PrP-null mice is
      increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here,
      we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal
      excitability, and in particular, the underlying ionic mechanism in hippocampal
      neurons cultured from P0 mouse pups. We found that the absence of PrP(C)
      profoundly affected the firing properties of cultured hippocampal neurons in the
      presence of synaptic blockers. The membrane impedance was greater in PrP-null
      neurons, and this difference was abolished by the hyperpolarization-activated
      cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 MUM). HCN channel
      activity appeared to be functionally regulated by PrP(C). The amplitude of
      voltage sag, a characteristic of activating HCN channel current (I h), was
      decreased in null mice. Moreover, I h peak current was reduced, along with a
      hyperpolarizing shift in activation gating and slower kinetics. However, neither
      HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest
      that the absence of PrP downregulates the activity of HCN channels through
      activation of a cell signaling pathway rather than through direct interactions.
      This in turn contributes to an increase in membrane impedance to potentiate
      neuronal excitability. 

PMID- 27047339
TI  - Correlation between Cortical State and Locus Coeruleus Activity: Implications for
      Sensory Coding in Rat Barrel Cortex.
AB  - Cortical state modulates the background activity of cortical neurons, and their
      evoked response to sensory stimulation. Multiple mechanisms are involved in
      switching between cortical states including various neuromodulatory systems.
      Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem
      with widespread projections throughout the brain and modulates the activity of
      cells and networks. Here, we quantified the link between the LC spontaneous
      activity, cortical state and sensory processing in the rat vibrissal
      somatosensory "barrel" cortex (BC). We simultaneously recorded unit activity from
      LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief
      whisker deflections under urethane anesthesia. The ratio of low to high frequency
      components of EEG (referred to as the L/H ratio) was employed to identify
      cortical state. We found that the spontaneous activity of LC units exhibited a
      negative correlation with the L/H ratio. Cross-correlation analysis revealed that
      changes in LC firing preceded changes in the cortical state: the correlation of
      the LC firing profile with the L/H ratio was maximal at an average lag of -1.2 s.
      We further quantified BC neuronal responses to whisker stimulation during the
      synchronized and desynchronized states. In the desynchronized state, BC neurons
      showed lower stimulus detection threshold, higher response fidelity, and shorter
      response latency. The most prominent change was observed in the late phase of BC
      evoked activity (100-400 ms post stimulus onset): almost every BC unit exhibited
      a greater late response during the desynchronized state. Categorization of the BC
      evoked responses based on LC activity (into high and low LC discharge rates)
      resulted in highly similar response profiles compared to categorization based on
      the cortical state (low and high L/H ratios). These findings provide evidence for
      the involvement of the LC neuromodulatory system in desynchronization of cortical
      state and the consequent enhancement of sensory coding efficiency. 

PMID- 27047340
TI  - Spatio-Temporal Characteristics of Inhibition Mapped by Optical Stimulation in
      Mouse Olfactory Bulb.
AB  - Mitral and tufted cells (MTCs) of the mammalian olfactory bulb are connected via
      dendrodendritic synapses with inhibitory interneurons in the external plexiform
      layer. The range, spatial layout, and temporal properties of inhibitory
      interactions between MTCs mediated by inhibitory interneurons remain unclear.
      Therefore, we tested for inhibitory interactions using an optogenetic approach.
      We optically stimulated MTCs expressing channelrhodopsin-2 in transgenic mice,
      while recording from individual MTCs in juxtacellular or whole-cell configuration
      in vivo. We used a spatial noise stimulus for mapping interactions between MTCs
      belonging to different glomeruli in the dorsal bulb. Analyzing firing responses
      of MTCs to the stimulus, we did not find robust lateral inhibitory effects that
      were spatially specific. However, analysis of sub-threshold changes in the
      membrane potential revealed evidence for inhibitory interactions between MTCs
      that belong to different glomerular units. These lateral inhibitory effects were
      short-lived and spatially specific. MTC response maps showed hyperpolarizing
      effects radially extending over more than five glomerular diameters. The
      inhibitory maps exhibited non-symmetrical yet distance-dependent characteristics.

PMID- 27047341
TI  - Repertoires of Spike Avalanches Are Modulated by Behavior and Novelty.
AB  - Neuronal avalanches measured as consecutive bouts of thresholded field potentials
      represent a statistical signature that the brain operates near a critical point.
      In theory, criticality optimizes stimulus sensitivity, information transmission,
      computational capability and mnemonic repertoires size. Field potential
      avalanches recorded via multielectrode arrays from cortical slice cultures are
      repeatable spatiotemporal activity patterns. It remains unclear whether
      avalanches of action potentials observed in forebrain regions of freely-behaving
      rats also form recursive repertoires, and whether these have any behavioral
      relevance. Here, we show that spike avalanches, recorded from hippocampus (HP)
      and sensory neocortex of freely-behaving rats, constitute distinct families of
      recursive spatiotemporal patterns. A significant number of those patterns were
      specific to a behavioral state. Although avalanches produced during sleep were
      mostly similar to others that occurred during waking, the repertoire of patterns
      recruited during sleep differed significantly from that of waking. More
      importantly, exposure to novel objects increased the rate at which new patterns
      arose, also leading to changes in post-exposure repertoires, which were
      significantly different from those before the exposure. A significant number of
      families occurred exclusively during periods of whisker contact with objects, but
      few were associated with specific objects. Altogether, the results provide
      original evidence linking behavior and criticality at the spike level: spike
      avalanches form repertoires that emerge in waking, recur during sleep, are
      diversified by novelty and contribute to object representation. 

PMID- 27047343
TI  - Evidence for Dynamic Network Regulation of Drosophila Photoreceptor Function from
      Mutants Lacking the Neurotransmitter Histamine.
AB  - Synaptic feedback from interneurons to photoreceptors can help to optimize visual
      information flow by balancing its allocation on retinal pathways under changing
      light conditions. But little is known about how this critical network operation
      is regulated dynamically. Here, we investigate this question by comparing
      signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors
      to those of the hdc (JK910) mutant, which lacks the neurotransmitter histamine
      and therefore cannot transmit information to interneurons. Recordings show that
      hdc (JK910) photoreceptors sample similar amounts of information from
      naturalistic stimulation to wild-type photoreceptors, but this information is
      packaged in smaller responses, especially under bright illumination. Analyses
      reveal how these altered dynamics primarily resulted from network overload that
      affected hdc (JK910) photoreceptors in two ways. First, the missing inhibitory
      histamine input to interneurons almost certainly depolarized them irrevocably,
      which in turn increased their excitatory feedback to hdc (JK910) R1-R6s. This
      tonic excitation depolarized the photoreceptors to artificially high potentials,
      reducing their operational range. Second, rescuing histamine input to
      interneurons in hdc (JK910) mutant also restored their normal phasic feedback
      modulation to R1-R6s, causing photoreceptor output to accentuate dynamic
      intensity differences at bright illumination, similar to the wild-type. These
      results provide mechanistic explanations of how synaptic feedback connections
      optimize information packaging in photoreceptor output and novel insight into the
      operation and design of dynamic network regulation of sensory neurons. 

PMID- 27047344
TI  - Cerebellar Nuclei Neurons Show Only Small Excitatory Responses to Optogenetic
      Olivary Stimulation in Transgenic Mice: In Vivo and In Vitro Studies.
AB  - To study the olivary input to the cerebellar nuclei (CN) we used optogenetic
      stimulation in transgenic mice expressing channelrhodopsin-2 (ChR2) in olivary
      neurons. We obtained in vivo extracellular Purkinje cell (PC) and CN recordings
      in anesthetized mice while stimulating the contralateral inferior olive (IO) with
      a blue laser (single pulse, 10-50 ms duration). Peri-stimulus histograms (PSTHs)
      were constructed to show the spike rate changes after optical stimulation. Among
      29 CN neurons recorded, 15 showed a decrease in spike rate of variable strength
      and duration, and only 1 showed a transient spiking response. These results
      suggest that direct olivary input to CN neurons is usually overridden by stronger
      PC inhibition triggered by climbing fiber responses. To further investigate the
      direct input from the climbing fiber collaterals we also conducted whole cell
      recordings in brain slices, where we used local stimulation with blue light. Due
      to the expression of ChR2 in PC axons as well as the IO in our transgenic line,
      strong inhibitory responses could be readily triggered with optical stimulation
      (13 of 15 neurons). After blocking this inhibition with GABAzine, only in 5 of 13
      CN neurons weak excitatory responses were revealed. Therefore our in vitro
      results support the in vivo findings that the excitatory input to CN neurons from
      climbing fiber collaterals in adult mice is masked by the inhibition under normal
      conditions. 

PMID- 27047342
TI  - Sensory Activation of Command Cells for Locomotion and Modulatory Mechanisms:
      Lessons from Lampreys.
AB  - Sensorimotor transformation is one of the most fundamental and ubiquitous
      functions of the central nervous system (CNS). Although the general organization
      of the locomotor neural circuitry is relatively well understood, less is known
      about its activation by sensory inputs and its modulation. Utilizing the lamprey
      model, a detailed understanding of sensorimotor integration in vertebrates is
      emerging. In this article, we explore how the vertebrate CNS integrates sensory
      signals to generate motor behavior by examining the pathways and neural
      mechanisms involved in the transformation of cutaneous and olfactory inputs into
      motor output in the lamprey. We then review how 5-hydroxytryptamine (5-HT) acts
      on these systems by modulating both sensory inputs and motor output. A
      comprehensive review of this fundamental topic should provide a useful framework
      in the fields of motor control, sensorimotor integration and neuromodulation. 

PMID- 27047345
TI  - Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased
      Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2
      after Multiple Dengue Infections in Callithrix penicillata.
AB  - It is known that microglial morphology and function are related, but few studies
      have explored the subtleties of microglial morphological changes in response to
      specific pathogens. In the present report we quantitated microglia morphological
      changes in a monkey model of dengue disease with virus CNS invasion. To mimic
      multiple infections that usually occur in endemic areas, where higher dengue
      infection incidence and abundant mosquito vectors carrying different serotypes
      coexist, subjects received once a week subcutaneous injections of DENV3 (genotype
      III)-infected culture supernatant followed 24 h later by an injection of anti
      DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or
      no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1.
      Random and systematic microglial samples were taken from the polymorphic layer of
      dentate gyrus for 3-D reconstructions, where we found intense immunostaining for
      TNFalpha and DENV3 virus antigens. We submitted all bi- or multimodal
      morphological parameters of microglia to hierarchical cluster analysis and found
      two major morphological phenotypes designated types I and II. Compared to type I
      (stage 1), type II microglia were more complex; displaying higher number of
      nodes, processes and trees and larger surface area and volumes (stage 2). Type II
      microglia were found only in infected monkeys, whereas type I microglia was found
      in both control and infected subjects. Hierarchical cluster analysis of
      morphological parameters of 3-D reconstructions of random and systematic selected
      samples in control and ADE dengue infected monkeys suggests that microglia
      morphological changes from stage 1 to stage 2 may not be continuous. 

PMID- 27047346
TI  - Distinctive Features of the Human Marginal Zone and Cajal-Retzius Cells:
      Comparison of Morphological and Immunocytochemical Features at Midgestation.
AB  - Despite a long history of research of cortical marginal zone (MZ) organization
      and development, a number of issues remain unresolved. One particular issue is
      the problem of Cajal-Retzius cells (C-R) identification. It is currently based on
      morphology and Reelin expression. The aim of this research is to investigate MZ
      cytoarchitectonics and Reelin-producing cells morphotypes in the superior
      temporal, pre- and postcentral cortex at GW24-26. We used Reelin (Reln) as the
      marker for C-R cells and microtubule-associated protein 2 (MAP2) and
      neurofilament heavy chain protein (N200) as markers of neuronal maturation. The
      MZ of all of the investigated areas had the distinct cytoarchitectonic of
      alternating cell sparse (MZP, SR) and cell dense (SGL, DGL) layers. The
      distribution of the neuromarkers across the MZ also showed layer specificity.
      MAP2-positive cells were only found in the SGL. N200 and Reelin-positive neurons
      in the MZP. N200-positive processes were forming a plexus at the DGL level. All
      of the N200-positive neurons found were in the MZP and had distinctive
      morphological features of C-R cells. All of the N200-positive neurons in MZ were
      also positive for Reelin, whereas MAP2-positive cells lack Reelin. Thus, the
      joint use of two immunomarkers allowed us to discern the C-R cells based on their
      morphotype and neurochemistry and indicate that the Reelin-positive cells of MZ
      at 24-26 GW were morphologically C-R cells. In the current study, we identified
      three C-R cells morphotypes. Using a 3D reconstruction, we made sure that all of
      them belonged to the single morphotype of triangular C-R cells. This approach
      will allow future studies to separate C-R cells from other Reelin-producing
      neurons which appear at later corticogenesis stages. In addition, our findings
      support the assumption that a plexus could be formed not only with C-R cells
      processes but also possibly by other cell processes by the poorly researched DGL,
      which is only allocated as a part of the human MZ. 

PMID- 27047347
TI  - A Simple and Efficient In Vivo Non-viral RNA Transfection Method for Labeling the
      Whole Axonal Tree of Individual Adult Long-Range Projection Neurons.
AB  - We report a highly efficient, simple, and non-infective method for labeling
      individual long-range projection neurons (LRPNs) in a specific location with
      enough sparseness and intensity to allow complete and unambiguous reconstructions
      of their entire axonal tree. The method is based on the "in vivo" transfection of
      a large RNA construct that drives the massive expression of green fluorescent
      protein. The method combines two components: injection of a small volume of a
      hyperosmolar NaCl solution containing the Pal-eGFP-Sindbis RNA construct (Furuta
      et al., 2001), followed by the application of high-frequency electric current
      pulses through the micropipette tip. We show that, although each component alone
      increases transfection efficacy, compared to simple volume injections of standard
      RNA solution, the highest efficacy (85.7%) is achieved by the combination of both
      components. In contrast with the infective viral Sindbis vector, RNA transfection
      occurs exclusively at the position of the injection micropipette tip. This method
      simplifies consistently labeling one or a few isolated neurons per brain, a
      strategy that allows unambiguously resolving and quantifying the brain-wide and
      often multi-branched monosynaptic circuits created by LRPNs. 

PMID- 27047348
TI  - Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain
      as Revealed by Constrained Spherical Deconvolution Tractography.
AB  - The connections between the cerebellum and basal ganglia were assumed to occur at
      the level of neocortex. However evidences from animal data have challenged this
      old perspective showing extensive subcortical pathways linking the cerebellum
      with the basal ganglia. Here we tested the hypothesis if these connections also
      exist between the cerebellum and basal ganglia in the human brain by using
      diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects
      were analyzed by using constrained spherical deconvolution technique obtained
      with a 3T magnetic resonance imaging scanner. We found extensive connections
      running between the subthalamic nucleus and cerebellar cortex and, as novel
      result, we demonstrated a direct route linking the dentate nucleus to the
      internal globus pallidus as well as to the substantia nigra. These findings may
      open a new scenario on the interpretation of basal ganglia disorders. 

PMID- 27047349
TI  - Multimodal Diffusion-MRI and MEG Assessment of Auditory and Language System
      Development in Autism Spectrum Disorder.
AB  - BACKGROUND: Auditory processing and language impairments are prominent in
      children with autism spectrum disorder (ASD). The present study integrated
      diffusion MR measures of white-matter microstructure and magnetoencephalography
      (MEG) measures of cortical dynamics to investigate associations between brain
      structure and function within auditory and language systems in ASD. Based on
      previous findings, abnormal structure-function relationships in auditory and
      language systems in ASD were hypothesized. METHODS: Evaluable neuroimaging data
      was obtained from 44 typically developing (TD) children (mean age 10.4 +/- 2.4
      years) and 95 children with ASD (mean age 10.2 +/- 2.6 years). Diffusion MR
      tractography was used to delineate and quantitatively assess the auditory
      radiation and arcuate fasciculus segments of the auditory and language systems.
      MEG was used to measure (1) superior temporal gyrus auditory evoked M100 latency
      in response to pure-tone stimuli as an indicator of auditory system conduction
      velocity, and (2) auditory vowel-contrast mismatch field (MMF) latency as a
      passive probe of early linguistic processes. RESULTS: Atypical development of
      white matter and cortical function, along with atypical lateralization, were
      present in ASD. In both auditory and language systems, white matter integrity and
      cortical electrophysiology were found to be coupled in typically developing
      children, with white matter microstructural features contributing significantly
      to electrophysiological response latencies. However, in ASD, we observed
      uncoupled structure-function relationships in both auditory and language systems.
      Regression analyses in ASD indicated that factors other than white-matter
      microstructure additionally contribute to the latency of neural evoked responses
      and ultimately behavior. RESULTS also indicated that whereas delayed M100 is a
      marker for ASD severity, MMF delay is more associated with language impairment.
      CONCLUSION: Present findings suggest atypical development of primary auditory as
      well as auditory language systems in ASD. Findings demonstrate the need for
      additional multimodal studies to better characterize the different structural
      features (white matter, gray matter, neurochemical concentration) that contribute
      to brain activity, both in typical development and in ASD. Finally, the neural
      latency measures were found to be of clinical significance, with M100 associated
      with overall ASD severity, and with MMF latency associated with language
      performance.

PMID- 27047350
TI  - Whole Brain Imaging with Serial Two-Photon Tomography.
AB  - Imaging entire mouse brains at submicron resolution has historically been a
      challenging undertaking and largely confined to the province of dedicated
      atlasing initiatives. This has limited systematic investigations into important
      areas of neuroscience, such as neural circuits, brain mapping and
      neurodegeneration. In this article, we describe in detail Serial Two-Photon (STP)
      tomography, a robust, reliable method for imaging entire brains with histological
      detail. We provide examples of how the basic methodology can be extended to other
      imaging modalities, such as Optical Coherence Tomography (OCT), in order to
      provide unique contrast mechanisms. Furthermore, we provide a survey of the
      research that STP tomography has enabled in the field of neuroscience, provide
      examples of how this technology enables quantitative whole brain studies, and
      discuss the current limitations of STP tomography-based approaches. 

PMID- 27047351
TI  - The Neuroanatomical Basis for Posterior Superior Parietal Lobule Control
      Lateralization of Visuospatial Attention.
AB  - The right hemispheric dominance in visuospatial attention in human brain has been
      well established. Converging evidence has documented that ventral posterior
      parietal cortex (PPC) plays an important role in visuospatial attention. The role
      of dorsal PPC subregions, especially the superior parietal lobule (SPL) in
      visuospatial attention is still controversial. In the current study, we used
      repetitive transcranial magnetic stimulation (rTMS) and diffusion magnetic
      resonance imaging (MRI) techniques to test the role of posterior SPL in
      visuospatial attention and to investigate the potential neuroanatomical basis for
      right hemisphere dominance in visuospatial function. Transcranial magnetic
      stimulation (TMS) results unraveled that the right SPL predominantly mediated
      visuospatial attention compared to left SPL. Anatomical connections analyses
      between the posterior SPL and the intrahemispheric frontal subregions and the
      contralateral PPC revealed that right posterior SPL has stronger anatomical
      connections with the ipsilateral middle frontal gyrus (MFG), with the ipsilateral
      inferior frontal gyrus (IFG), and with contralateral PPC than that of the left
      posterior SPL. Furthermore, these asymmetric anatomical connections were closely
      related to behavioral performances. Our findings indicate that SPL plays a
      crucial role in regulating visuospatial attention, and dominance of visuospatial
      attention results from unbalanced interactions between the bilateral fronto
      parietal networks and the interhemispheric parietal network. 

PMID- 27047352
TI  - A Probabilistic Approach to Receptive Field Mapping in the Frontal Eye Fields.
AB  - Studies of the neuronal mechanisms of perisaccadic vision often lack the
      resolution needed to determine important changes in receptive field (RF)
      structure. Such limited analytical power can lead to inaccurate descriptions of
      visuomotor processing. To address this issue, we developed a precise,
      probabilistic technique that uses a generalized linear model (GLM) for mapping
      the visual RFs of frontal eye field (FEF) neurons during stable fixation (Mayo et
      al., 2015). We previously found that full-field RF maps could be obtained using 1
      8 dot stimuli presented at frame rates of 10-150 ms. FEF responses were generally
      robust to changes in the number of stimuli presented or the rate of presentation,
      which allowed us to visualize RFs over a range of spatial and temporal
      resolutions. Here, we compare the quality of RFs obtained over different stimulus
      and GLM parameters to facilitate future work on the detailed mapping of FEF RFs.
      We first evaluate the interactions between the number of stimuli presented per
      trial, the total number of trials, and the quality of RF mapping. Next, we vary
      the spatial resolution of our approach to illustrate the tradeoff between
      visualizing RF sub-structure and sampling at high resolutions. We then evaluate
      local smoothing as a possible correction for situations where under-sampling
      occurs. Finally, we provide a preliminary demonstration of the usefulness of a
      probabilistic approach for visualizing full-field perisaccadic RF shifts. Our
      results present a powerful, and perhaps necessary, framework for studying
      perisaccadic vision that is applicable to FEF and possibly other visuomotor
      regions of the brain. 

PMID- 27047353
TI  - Rehabilitation of Communicative Abilities in Patients with a History of TBI:
      Behavioral Improvements and Cerebral Changes in Resting-State Activity.
AB  - A targeted training program for the rehabilitation of communicative abilities
      Cognitive Pragmatic Treatment (CPT)-has been developed and previously tested on a
      sample of patients with traumatic brain injury (TBI), whose performance was found
      to have improved. Since cortical plasticity has been recognized as the main
      mechanism of functional recovery, we investigated whether and how behavioral
      improvements following the training program are accompanied by brain
      modifications. Eight TBI patients took part in the training program and were
      behaviorally assessed pre- and post-treatment; six of these patients were also
      evaluated with pre- and post-treatment resting state (rs) functional magnetic
      resonance imaging (fMRI). At the end of the rehabilitation program patients
      showed improvement in overall communicative performance, in both comprehension
      and production tasks. A follow-up retest revealed the stability of these results
      3 months after completing the training program. At the brain level, we found
      significant increases in the amplitude of low frequency fluctuation (ALFF) index
      in the bilateral precentral gyrus, in the right middle and superior temporal
      gyri, in the right cingulate gyrus, and in the left inferior parietal lobule. We
      discuss these differences of brain activity in terms of their possible
      contribution to promoting recovery. 

PMID- 27047354
TI  - Relationship of the Chemokine, CXCL12, to Effects of Dietary Fat on Feeding
      Related Behaviors and Hypothalamic Neuropeptide Systems.
AB  - The intake of a high fat diet (HFD), in addition to stimulating orexigenic
      neuropeptides in the hypothalamus while promoting overeating and reducing
      locomotor behavior, is known to increase inflammatory mediators that modulate
      neuronal systems in the brain. To understand the involvement of chemokines in the
      effects of a HFD, we examined in rats whether HFD intake affects a specific
      chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, in the hypothalamus
      together with the neuropeptides and whether CXCL12 itself acts similarly to a HFD
      in stimulating the neuropeptides and altering ingestion and locomotor behavior.
      Compared to low-fat chow, a HFD for 5 days significantly increased the expression
      of CXCL12 and its receptors, in both the paraventricular nucleus (PVN) where the
      neuropeptides enkephalin (ENK) and galanin were also stimulated and the
      perifornical lateral hypothalamus (PFLH) where orexin (OX) and melanin
      concentrating hormone (MCH) were increased. In contrast, the HFD had no impact on
      expression of CXCL12 or its receptors in the arcuate nucleus (ARC) where the
      carbohydrate-related peptide, neuropeptide Y (NPY), was suppressed. Analysis of
      protein levels revealed a similar stimulatory effect of a HFD on CXCL12 levels in
      the PVN and PFLH, as well as in blood, and an increase in the number of CXCR4
      positive cells in the PVN. In the ARC, in contrast, levels of CXCL12 and number
      of CXCR4-positive cells were too low to measure. When centrally administered,
      CXCL12 was found to have similar effects to a HFD. Injection of CXCL12 into the
      third cerebral ventricle immediately anterior to the hypothalamus significantly
      stimulated the ingestion of a HFD, reduced novelty-induced locomotor activity,
      and increased expression of ENK in the PVN where the CXCR4 receptors were dense.
      It had no impact, however, on NPY in the ARC or on OX and MCH in the PFLH where
      the CXCR4 receptors were not detected. These results, showing CXCL12 in the
      hypothalamus to be stimulated by a HFD and to mimic the effects of the HFD where
      its receptors are located, suggest that this chemokine system may have a role in
      mediating both the neuronal and behavioral effects induced by a fat-rich diet. 

PMID- 27047355
TI  - Prolonged Consumption of Sucrose in a Binge-Like Manner, Alters the Morphology of
      Medium Spiny Neurons in the Nucleus Accumbens Shell.
AB  - The modern diet has become highly sweetened, resulting in unprecedented levels of
      sugar consumption, particularly among adolescents. While chronic long-term sugar
      intake is known to contribute to the development of metabolic disorders including
      obesity and type II diabetes, little is known regarding the direct consequences
      of long-term, binge-like sugar consumption on the brain. Because sugar can cause
      the release of dopamine in the nucleus accumbens (NAc) similarly to drugs of
      abuse, we investigated changes in the morphology of neurons in this brain region
      following short- (4 weeks) and long-term (12 weeks) binge-like sucrose
      consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox
      staining to impregnate medium spiny neurons (MSNs) from the NAc core and shell of
      short- and long-term sucrose consuming rats and compared these to age-matched
      water controls. We show that prolonged binge-like sucrose consumption
      significantly decreased the total dendritic length of NAc shell MSNs compared to
      age-matched control rats. We also found that the restructuring of these neurons
      resulted primarily from reduced distal dendritic complexity. Conversely, we
      observed increased spine densities at the distal branch orders of NAc shell MSNs
      from long-term sucrose consuming rats. Combined, these results highlight the
      neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN
      morphology. 

PMID- 27047356
TI  - Weak Broadband Electromagnetic Fields are More Disruptive to Magnetic Compass
      Orientation in a Night-Migratory Songbird (Erithacus rubecula) than Strong Narrow
      Band Fields.
AB  - Magnetic compass orientation in night-migratory songbirds is embedded in the
      visual system and seems to be based on a light-dependent radical pair mechanism.
      Recent findings suggest that both broadband electromagnetic fields ranging from
      ~2 kHz to ~9 MHz and narrow-band fields at the so-called Larmor frequency for a
      free electron in the Earth's magnetic field can disrupt this mechanism. However,
      due to local magnetic fields generated by nuclear spins, effects specific to the
      Larmor frequency are difficult to understand considering that the primary sensory
      molecule should be organic and probably a protein. We therefore constructed a
      purpose-built laboratory and tested the orientation capabilities of European
      robins in an electromagnetically silent environment, under the specific influence
      of four different oscillating narrow-band electromagnetic fields, at the Larmor
      frequency, double the Larmor frequency, 1.315 MHz or 50 Hz, and in the presence
      of broadband electromagnetic noise covering the range from ~2 kHz to ~9 MHz. Our
      results indicated that the magnetic compass orientation of European robins could
      not be disrupted by any of the relatively strong narrow-band electromagnetic
      fields employed here, but that the weak broadband field very efficiently
      disrupted their orientation. 

PMID- 27047357
TI  - Commentary: Anatomical constitution of sense organs as a marker of mental
      disorders.

PMID- 27047358
TI  - Look at the Beat, Feel the Meter: Top-Down Effects of Meter Induction on Auditory
      and Visual Modalities.
AB  - Recent research has demonstrated top-down effects on meter induction in the
      auditory modality. However, little is known about these effects in the visual
      domain, especially without the involvement of motor acts such as tapping. In the
      present study, we aim to assess whether the projection of meter on auditory beats
      is also present in the visual domain. We asked 16 musicians to internally project
      binary (i.e., a strong-weak pattern) and ternary (i.e., a strong-weak-weak
      pattern) meter onto separate, but analog, visual and auditory isochronous
      stimuli. Participants were presented with sequences of tones or blinking circular
      shapes (i.e., flashes) at 2.4 Hz while their electrophysiological responses were
      recorded. A frequency analysis of the elicited steady-state evoked potentials
      allowed us to compare the frequencies of the beat (2.4 Hz), its first harmonic
      (4.8 Hz), the binary subharmonic (1.2 Hz), and the ternary subharmonic (0.8 Hz)
      within and across modalities. Taking the amplitude spectra into account, we
      observed an enhancement of the amplitude at 0.8 Hz in the ternary condition for
      both modalities, suggesting meter induction across modalities. There was an
      interaction between modality and voltage at 2.4 and 4.8 Hz. Looking at the power
      spectra, we also observed significant differences from zero in the auditory, but
      not in the visual, binary condition at 1.2 Hz. These findings suggest that meter
      processing is modulated by top-down mechanisms that interact with our perception
      of rhythmic events and that such modulation can also be found in the visual
      domain. The reported cross-modal effects of meter may shed light on the origins
      of our timing mechanisms, partially developed in primates and allowing humans to
      synchronize across modalities accurately. 

PMID- 27047359
TI  - Liking versus Complexity: Decomposing the Inverted U-curve.
AB  - The relationship between liking and stimulus complexity is commonly reported to
      follow an inverted U-curve. However, large individual differences among
      complexity preferences of participants have frequently been observed since the
      earliest studies on the topic. The common use of across-participant analysis
      methods that ignore these large individual differences in aesthetic preferences
      gives an impression of high agreement between individuals. In this study, we
      collected ratings of liking and perceived complexity from 30 participants for a
      set of digitally generated grayscale images. In addition, we calculated an
      objective measure of complexity for each image. Our results reveal that the
      inverted U-curve relationship between liking and stimulus complexity comes about
      as the combination of different individual liking functions. Specifically, after
      automatically clustering the participants based on their liking ratings, we
      determined that one group of participants in our sample had increasingly lower
      liking ratings for increasingly more complex stimuli, while a second group of
      participants had increasingly higher liking ratings for increasingly more complex
      stimuli. Based on our findings, we call for a focus on the individual differences
      in aesthetic preferences, adoption of alternative analysis methods that would
      account for these differences and a re-evaluation of established rules of human
      aesthetic preferences. 

PMID- 27047360
TI  - Experiential and Doctrinal Religious Knowledge Categorization in Parkinson's
      Disease: Behavioral and Brain Correlates.
AB  - Recent studies suggest changes in religious cognition in a subgroup of patients
      with Parkinson's disease (PD e.g., Butler et al., 2011). It is unclear whether
      this deficit extends to both doctrinal and experiential categorization forms of
      religious cognition. Kapogiannis et al. (2009b) dissociated experiential and
      doctrinal religious knowledge to different neural networks using fMRI. We
      examined Kapogiannis' dissociation against the background of PD side of onset
      (LOPD, ROPD), assessing performance both On- and Off-medication. In the
      behavioral portion of the study, we used a statement classification task in
      combination with scholar derived test sets for experiential and doctrinal
      religious knowledge categorization in conjunction with neuropsychological
      measures. In the neuroimaging portion of the study, we expanded on Kapogiannis'
      study by examining the same networks in PD. The behavioral data revealed that all
      groups rated (categorized) the scholar derived tests of experiential and
      doctrinal significantly differently than the scholars. All groups, including the
      scholars, classified more phrases as doctrinal than experiential. Religious
      cognition differed in the PD groups: those with PD Off-medication and LOPD Off
      medication comprehended scholar defined experiential phrases with more
      difficulty, making them more likely to be classified as mixed or doctrinal. This
      was in contrast to the subjective frequency of classification of phrases as
      experiential paired with a cognitive decline in PD Off-medication; whereas PD On
      medication showed a positive correlation with cognitive state and subjective
      doctrinal classification. For ROPD, cognitive state was associated with
      subjective experiential and doctrinal frequency of classification. With more
      intact intellect, there was a greater likelihood of classifying phrases
      subjectively as mixed, and the converse for experiential. Furthermore,
      religiosity negatively predicted subjective doctrinal frequency in LOPD, with the
      converse in ROPD. In fcMRI in PD, we found resting state functional intrinsic
      connectivity of reward networks associated with classification of statements
      using seeds in bilateral nucleus accumbens in PD. For experiential regressors,
      there was a negative correlation in bilateral frontal lobes paired with a
      positive correlation in left occipital visual areas (BAs 17, 18). For doctrinal
      regressors, there was a positive correlation in right BA 20. 

PMID- 27047361
TI  - Pushing the Limits: Cognitive, Affective, and Neural Plasticity Revealed by an
      Intensive Multifaceted Intervention.
AB  - Scientific understanding of how much the adult brain can be shaped by experience
      requires examination of how multiple influences combine to elicit cognitive,
      affective, and neural plasticity. Using an intensive multifaceted intervention,
      we discovered that substantial and enduring improvements can occur in parallel
      across multiple cognitive and neuroimaging measures in healthy young adults. The
      intervention elicited substantial improvements in physical health, working
      memory, standardized test performance, mood, self-esteem, self-efficacy,
      mindfulness, and life satisfaction. Improvements in mindfulness were associated
      with increased degree centrality of the insula, greater functional connectivity
      between insula and somatosensory cortex, and reduced functional connectivity
      between posterior cingulate cortex (PCC) and somatosensory cortex. Improvements
      in working memory and reading comprehension were associated with increased degree
      centrality of a region within the middle temporal gyrus (MTG) that was
      extensively and predominately integrated with the executive control network. The
      scope and magnitude of the observed improvements represent the most extensive
      demonstration to date of the considerable human capacity for change. These
      findings point to higher limits for rapid and concurrent cognitive, affective,
      and neural plasticity than is widely assumed. 

PMID- 27047362
TI  - Barack Obama Blindness (BOB): Absence of Visual Awareness to a Single Object.
AB  - In two experiments, we evaluated whether a perceiver's prior expectations could
      alone obliterate his or her awareness of a salient visual stimulus. To establish
      expectancy, observers first made a demanding visual discrimination on each of
      three baseline trials. Then, on a fourth, critical trial, a single, salient and
      highly visible object appeared in full view at the center of the visual field and
      in the absence of any competing visual input. Surprisingly, fully half of the
      participants were unaware of the solitary object in front of their eyes.
      Dramatically, observers were blind even when the only stimulus on display was the
      face of U.S. President Barack Obama. We term this novel, counterintuitive
      phenomenon, Barack Obama Blindness (BOB). Employing a method that rules out
      putative memory effects by probing awareness immediately after presentation of
      the critical stimulus, we demonstrate that the BOB effect is a true failure of
      conscious vision. 

PMID- 27047364
TI  - The Self-Pleasantness Judgment Modulates the Encoding Performance and the Default
      Mode Network Activity.
AB  - In this functional magnetic resonance imaging (fMRI) study, we evaluated the
      effect of self-relevance on cerebral activity and behavioral performance during
      an incidental encoding task. Recent findings suggest that pleasantness judgments
      reliably induce self-oriented (internal) thoughts and increase default mode
      network (DMN) activity. We hypothesized that this increase in DMN activity would
      relate to increased memory recognition for pleasantly-judged stimuli (which
      depend on internally-oriented attention) but decreased recognition for
      unpleasantly-judged items (which depend on externally-oriented attention). To
      test this hypothesis, brain activity was recorded from 21 healthy participants
      while they performed a pleasantness judgment requiring them to rate visual
      stimuli as pleasant or unpleasant. One hour later, participants performed a
      surprise memory recognition test outside of the scanner. Thus, we were able to
      evaluate the effects of pleasant and unpleasant judgments on cerebral activity
      and incidental encoding. The behavioral results showed that memory recognition
      was better for items rated as pleasant than items rated as unpleasant. The whole
      brain analysis indicated that successful encoding (SE) activates the inferior
      frontal and lateral temporal cortices, whereas unsuccessful encoding (UE)
      recruits two key medial posterior DMN regions, the posterior cingulate cortex
      (PCC) and precuneus (PCU). A region of interest (ROI) analysis including classic
      DMN areas, revealed significantly greater involvement of the medial prefrontal
      cortex (mPFC) in pleasant compared to unpleasant judgments, suggesting this
      region's involvement in self-referential (i.e., internal) processing. This area
      may be responsible for the greater recognition performance seen for pleasant
      stimuli. Furthermore, a significant interaction between the encoding performance
      (successful vs. unsuccessful) and pleasantness was observed for the PCC, PCU and
      inferior frontal gyrus (IFG). Overall, our results suggest the involvement of
      medial frontal and parietal DMN regions during the evaluation of self-referential
      pleasantness. We discuss these results in terms of the introspective referential
      of pleasantness judgments and the differential brain modulation based on
      internally- vs. externally-oriented attention during encoding. 

PMID- 27047363
TI  - The Oscillopathic Nature of Language Deficits in Autism: From Genes to Language
      Evolution.
AB  - Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders
      involving a number of deficits to linguistic cognition. The gap between genetics
      and the pathophysiology of ASD remains open, in particular regarding its
      distinctive linguistic profile. The goal of this article is to attempt to bridge
      this gap, focusing on how the autistic brain processes language, particularly
      through the perspective of brain rhythms. Due to the phenomenon of pleiotropy,
      which may take some decades to overcome, we believe that studies of brain
      rhythms, which are not faced with problems of this scale, may constitute a more
      tractable route to interpreting language deficits in ASD and eventually other
      neurocognitive disorders. Building on recent attempts to link neural oscillations
      to certain computational primitives of language, we show that interpreting
      language deficits in ASD as oscillopathic traits is a potentially fruitful way to
      construct successful endophenotypes of this condition. Additionally, we will show
      that candidate genes for ASD are overrepresented among the genes that played a
      role in the evolution of language. These genes include (and are related to) genes
      involved in brain rhythmicity. We hope that the type of steps taken here will
      additionally lead to a better understanding of the comorbidity, heterogeneity,
      and variability of ASD, and may help achieve a better treatment of the affected
      populations. 

PMID- 27047365
TI  - Consequences of Beauty: Effects of Rater Sex and Sexual Orientation on the Visual
      Exploration and Evaluation of Attractiveness in Real World Scenes.
AB  - One of the key behavioral effects of attractiveness is increased visual attention
      to attractive people. This effect is often explained in terms of evolutionary
      adaptations, such as attractiveness being an indicator of good health. Other
      factors could influence this effect. In the present study, we explored the
      modulating role of sexual orientation on the effects of attractiveness on
      exploratory visual behavior. Heterosexual and homosexual men and women viewed
      natural-looking scenes that depicted either two women or two men who varied
      systematically in levels of attractiveness (based on a pre-study). Participants'
      eye movements and attractiveness ratings toward the faces of the depicted people
      were recorded. The results showed that although attractiveness had the largest
      influence on participants' behaviors, participants' sexual orientations strongly
      modulated the effects. With the exception of homosexual women, all participant
      groups looked longer and more often at attractive faces that corresponded with
      their sexual orientations. Interestingly, heterosexual and homosexual men and
      homosexual women looked longer and more often at the less attractive face of
      their non-preferred sex than the less attractive face of their preferred sex,
      evidence that less attractive faces of the preferred sex might have an aversive
      character. These findings provide evidence for the important role that sexual
      orientation plays in guiding visual exploratory behavior and evaluations of the
      attractiveness of others. 

PMID- 27047366
TI  - Electrophysiological Evidence for Domain-General Processes in Task-Switching.
AB  - The ability to flexibly switch between tasks is a hallmark of cognitive control.
      Despite previous studies that have investigated whether different task-switching
      types would be mediated by distinct or overlapping neural mechanisms, no
      definitive consensus has been reached on this question yet. Here, we aimed at
      directly addressing this issue by recording the event-related potentials (ERPs)
      elicited by two types of task-switching occurring in the context of spatial and
      verbal cognitive domains. Source analysis was also applied to the ERP data in
      order to track the spatial dynamics of brain activity underlying task-switching
      abilities. In separate blocks of trials, participants had to perform either
      spatial or verbal switching tasks both of which employed the same type of
      stimuli. The ERP analysis, which was carried out through a channel- and time
      uninformed mass univariate approach, showed no significant differences between
      the spatial and verbal domains in the modulation of switch and repeat trials.
      Specifically, relative to repeat trials, switch trials in both domains were
      associated with a first larger positivity developing over left parieto-occipital
      electrodes and with a subsequent larger negativity distributed over mid-left
      fronto-central sites. The source analysis reconstruction for the two ERP
      components complemented these findings by highlighting the involvement of left
      lateralized prefrontal areas in task-switching. Overall, our results join and
      extend recent research confirming the existence of left-lateralized domain
      general task-switching processes. 

PMID- 27047367
TI  - Mechanisms of Self-Sustained Oscillatory States in Hierarchical Modular Networks
      with Mixtures of Electrophysiological Cell Types.
AB  - In a network with a mixture of different electrophysiological types of neurons
      linked by excitatory and inhibitory connections, temporal evolution leads through
      repeated epochs of intensive global activity separated by intervals with low
      activity level. This behavior mimics "up" and "down" states, experimentally
      observed in cortical tissues in absence of external stimuli. We interpret global
      dynamical features in terms of individual dynamics of the neurons. In particular,
      we observe that the crucial role both in interruption and in resumption of global
      activity is played by distributions of the membrane recovery variable within the
      network. We also demonstrate that the behavior of neurons is more influenced by
      their presynaptic environment in the network than by their formal types, assigned
      in accordance with their response to constant current. 

PMID- 27047368
TI  - Harmonic Training and the Formation of Pitch Representation in a Neural Network
      Model of the Auditory Brain.
AB  - Attempting to explain the perceptual qualities of pitch has proven to be, and
      remains, a difficult problem. The wide range of sounds which elicit pitch and a
      lack of agreement across neurophysiological studies on how pitch is encoded by
      the brain have made this attempt more difficult. In describing the potential
      neural mechanisms by which pitch may be processed, a number of neural networks
      have been proposed and implemented. However, no unsupervised neural networks with
      biologically accurate cochlear inputs have yet been demonstrated. This paper
      proposes a simple system in which pitch representing neurons are produced in a
      biologically plausible setting. Purely unsupervised regimes of neural network
      learning are implemented and these prove to be sufficient in identifying the
      pitch of sounds with a variety of spectral profiles, including sounds with
      missing fundamental frequencies and iterated rippled noises. 

PMID- 27047369
TI  - SNAP-25, a Known Presynaptic Protein with Emerging Postsynaptic Functions.
AB  - A hallmark of synaptic specializations is their dependence on highly organized
      complexes of proteins that interact with each other. The loss or modification of
      key synaptic proteins directly affects the properties of such networks,
      ultimately impacting synaptic function. SNAP-25 is a component of the SNARE
      complex, which is central to synaptic vesicle exocytosis, and, by directly
      interacting with different calcium channels subunits, it negatively modulates
      neuronal voltage-gated calcium channels, thus regulating intracellular calcium
      dynamics. The SNAP-25 gene has been associated with distinct brain diseases,
      including Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia and
      bipolar disorder, indicating that the protein may act as a shared biological
      substrate among different "synaptopathies". The mechanisms by which alterations
      in SNAP-25 may concur to these psychiatric diseases are still undefined, although
      alterations in neurotransmitter release have been indicated as potential
      causative processes. This review summarizes recent work showing that SNAP-25 not
      only controls exo/endocytic processes at the presynaptic terminal, but also
      regulates postsynaptic receptor trafficking, spine morphogenesis, and plasticity,
      thus opening the possibility that SNAP-25 defects may contribute to psychiatric
      diseases by impacting not only presynaptic but also postsynaptic functions. 

PMID- 27047370
TI  - Working Memory Training and Speech in Noise Comprehension in Older Adults.
AB  - Understanding speech in the presence of background sound can be challenging for
      older adults. Speech comprehension in noise appears to depend on working memory
      and executive-control processes (e.g., Heald and Nusbaum, 2014), and their
      augmentation through training may have rehabilitative potential for age-related
      hearing loss. We examined the efficacy of adaptive working-memory training
      (Cogmed; Klingberg et al., 2002) in 24 older adults, assessing generalization to
      other working-memory tasks (near-transfer) and to other cognitive domains (far
      transfer) using a cognitive test battery, including the Reading Span test,
      sensitive to working memory (e.g., Daneman and Carpenter, 1980). We also assessed
      far transfer to speech-in-noise performance, including a closed-set sentence task
      (Kidd et al., 2008). To examine the effect of cognitive training on benefit
      obtained from semantic context, we also assessed transfer to open-set sentences;
      half were semantically coherent (high-context) and half were semantically
      anomalous (low-context). Subjects completed 25 sessions (0.5-1 h each; 5
      sessions/week) of both adaptive working memory training and placebo training over
      10 weeks in a crossover design. Subjects' scores on the adaptive working-memory
      training tasks improved as a result of training. However, training did not
      transfer to other working memory tasks, nor to tasks recruiting other cognitive
      domains. We did not observe any training-related improvement in speech-in-noise
      performance. Measures of working memory correlated with the intelligibility of
      low-context, but not high-context, sentences, suggesting that sentence context
      may reduce the load on working memory. The Reading Span test significantly
      correlated only with a test of visual episodic memory, suggesting that the
      Reading Span test is not a pure-test of working memory, as is commonly assumed. 

PMID- 27047371
TI  - Retrieval Deficiency in Brain Activity of Working Memory in Amnesic Mild
      Cognitive Impairment Patients: A Brain Event-Related Potentials Study.
AB  - In the early stage of Alzheimer disease (AD) or mild cognitive impairment (MCI),
      working memory (WM) deficiency is prominent and could be attributed to failure in
      encoding, maintenance or retrieval of information. However, evidence for a
      retention or retrieval deficit remains equivocal. It is also unclear what
      cognitive mechanism in WM is impaired in MCI or early AD. We enrolled 46 subjects
      from our Memory Clinics and community, with 24 amnesic MCI patients and 22 normal
      subjects. After neurological and cognitive assessments, they performed a classic
      delayed match to sample (DMS) task with simultaneous event-related potential
      (ERP) recorded. The ERPs in encoding and retrieval epoch during WM were analyzed
      separately. The latency and amplitude of every ERP component were compared
      between two groups, and then analyzed to explore their relationship with
      neuropsychological performance. Finally, the locations of maximal difference in
      cortex were calculated by standard low-resolution tomographic analysis. A total
      of five components were found: P1, N1, P2, N2, and P300. The amplitude of P2 and
      P300 was larger in normal subjects than in MCI patients only during retrieval,
      not encoding epoch, while the latency did not show statistical difference. The
      latency and amplitude of P1 and N1 were similar in two groups. P2 amplitude in
      the retrieval epoch positively correlated with memory test (auditory verbal
      learning test) and visual spatial score of Chinese Addenbrooke's Cognitive
      Examination-Revised (ACE-R), while P300 amplitude correlated with ACE-R. The
      activation difference in P2 time range was maximal at medial frontal gyrus.
      However, the difference in cortex activation during P300 time range did not show
      significance. The amplitude of P2 indicated deficiency in memory retrieval
      process, potentially due to dysfunction of central executive in WM model.
      Regarding the location of P2 during WM task, medial frontal plays important role
      in memory retrieval. The findings in the present study suggested that MCI
      patients have retrieval deficit, probably due to central executive based on
      medial frontal gyrus. Thus, it may provide new biomarker for early detection and
      intervention for aMCI. 

PMID- 27047372
TI  - In Vivo Detection of Amyloid Plaques by Gadolinium-Stained MRI Can Be Used to
      Demonstrate the Efficacy of an Anti-amyloid Immunotherapy.
AB  - Extracellular deposition of beta amyloid plaques is an early event associated to
      Alzheimer's disease. Here, we have used in vivo gadolinium-stained high
      resolution (29(*)29(*)117 MUm(3)) magnetic resonance imaging (MRI) to follow-up
      in a longitudinal way individual amyloid plaques in APP/PS1 mice and evaluate the
      efficacy of a new immunotherapy (SAR255952) directed against protofibrillar and
      fibrillary forms of Abeta. APP/PS1 mice were treated for 5 months between the age
      of 3.5 and 8.5 months. SAR255952 reduced amyloid load in 8.5-months-old animals,
      but not in 5.5-months animals compared to mice treated with a control antibody
      (DM4). Histological evaluation confirmed the reduction of amyloid load and
      revealed a lower density of amyloid plaques in 8.5-months SAR255952-treated
      animals. The longitudinal follow-up of individual amyloid plaques by MRI revealed
      that plaques that were visible at 5.5 months were still visible at 8.5 months in
      both SAR255952 and DM4-treated mice. This suggests that the amyloid load
      reduction induced by SAR255952 is related to a slowing down in the formation of
      new plaques rather than to the clearance of already formed plaques. 

PMID- 27047375
TI  - Frequency-Dependent Brain Regional Homogeneity Alterations in Patients with Mild
      Cognitive Impairment during Working Memory State Relative to Resting State.
AB  - Several studies have reported working memory deficits in patients with mild
      cognitive impairment (MCI). However, previous studies investigating the neural
      mechanisms of MCI have primarily focused on brain activity alterations during
      working memory tasks. No study to date has compared brain network alterations in
      the working memory state between MCI patients and normal control (NC) subjects.
      Therefore, using the index of regional homogeneity (ReHo), we explored brain
      network impairments in MCI patients during a working memory task relative to the
      resting state, and identified frequency-dependent effects in separate frequency
      bands.Our results indicate that, in MCI patients, ReHo is altered in the
      posterior cingulate cortex (PCC) in the slow-3 band (0.073-0.198 Hz), and in the
      bottom of the right occipital lobe and part of the right cerebellum, the right
      thalamus, a diffusing region in the bilateral prefrontal cortex (PFC), the left
      and right parietal-occipital regions, and the right angular gyrus in the slow-5
      band (0.01-0.027 Hz). Furthermore, in NCs, the value of ReHo in clusters
      belonging to the default mode network (DMN) decreased, while the value of ReHo in
      clusters belonging to the attentional network increased during the task state.
      However, this pattern was reversed in MCI patients, and was associated with
      decreased working memory performance. In addition, we identified altered
      functional connectivity of the abovementioned regions with other parts of the
      brain in MCI patients. This is the first study to compare frequency-dependent
      alterations of ReHo in MCI patients between resting and working memory states.
      The results provide a new perspective regarding the neural mechanisms of working
      memory deficits in MCI patients, and extend our knowledge of altered brain
      patterns in resting and task-evoked states. 

PMID- 27047373
TI  - Exercise Counteracts Aging-Related Memory Impairment: A Potential Role for the
      Astrocytic Metabolic Shuttle.
AB  - Age-related cognitive impairment has become one of the most common health threats
      in many countries. The biological substrate of cognition is the interconnection
      of neurons to form complex information processing networks. Experience-based
      alterations in the activities of these information processing networks lead to
      neuroadaptation, which is physically represented at the cellular level as
      synaptic plasticity. Although synaptic plasticity is known to be affected by
      aging, the underlying molecular mechanisms are not well described. Astrocytes, a
      glial cell type that is infrequently investigated in cognitive science, have
      emerged as energy suppliers which are necessary for meeting the abundant energy
      demand resulting from glutamatergic synaptic activity. Moreover, the concerted
      action of an astrocyte-neuron metabolic shuttle is essential for cognitive
      function; whereas, energetic incoordination between astrocytes and neurons may
      contribute to cognitive impairment. Whether altered function of the astrocyte
      neuron metabolic shuttle links aging to reduced synaptic plasticity is
      unexplored. However, accumulated evidence documents significant beneficial
      effects of long-term, regular exercise on cognition and synaptic plasticity.
      Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic
      shuttle by upregulation of astrocytic lactate transporter levels. This review
      summarizes previous findings related to the neuronal activity-dependent astrocyte
      neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape
      the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. 

PMID- 27047376
TI  - Hippocampal Pathway Plasticity Is Associated with the Ability to Form Novel
      Memories in Older Adults.
AB  - White matter deterioration in the aging human brain contributes to cognitive
      decline. The fornix as main efferent hippocampal pathway is one of the tracts
      most strongly associated with age-related memory impairment. Its deterioration
      may predict conversion to Alzheimer's dementia and its precursors. However, the
      associations between the ability to form novel memories, fornix microstructure
      and plasticity in response to training have never been tested. In the present
      study, 25 healthy older adults (15 women; mean age (SD): 69 (6) years) underwent
      an object-location training on three consecutive days. Behavioral outcome
      measures comprised recall performance on the training days, and on 1-day and 1
      month follow up assessments. MRI at 3 Tesla was assessed before and after
      training. Fornix microstructure was determined by fractional anisotropy and mean
      diffusivity (MD) values from diffusion tensor imaging (DTI). In addition,
      hippocampal volumes were extracted from high-resolution images; individual
      hippocampal masks were further aligned to DTI images to determine hippocampal
      microstructure. Using linear mixed model analysis, we found that the change in
      fornix FA from pre- to post-training assessment was significantly associated with
      training success. Neither baseline fornix microstructure nor hippocampal
      microstructure or volume changes were significantly associated with performance.
      Further, models including control task performance (auditory verbal learning) and
      control white matter tract microstructure (uncinate fasciculus and
      parahippocampal cingulum) did not yield significant associations. Our results
      confirm that hippocampal pathways respond to short-term cognitive training, and
      extend previous findings by demonstrating that the magnitude of training-induced
      structural changes is associated with behavioral success in older adults. This
      suggests that the amount of fornix plasticity may not only be behaviorally
      relevant, but also a potential sensitive biomarker for the success of training
      interventions aimed at improving memory formation in older adults, a hypothesis
      to be evaluated in future studies. 

PMID- 27047374
TI  - G Protein-Coupled Receptors (GPCRs) in Alzheimer's Disease: A Focus on BACE1
      Related GPCRs.
AB  - The G protein coupled receptors (GPCRs) have been considered as one of the
      largest families of validated drug targets, which involve in almost overall
      physiological functions and pathological processes. Meanwhile, Alzheimer's
      disease (AD), the most common type of dementia, affects thinking, learning,
      memory and behavior of elderly people, that has become the hotspot nowadays for
      its increasing risks and incurability. The above fields have been intensively
      studied, and the link between the two has been demonstrated, whereas the way how
      GPCRs perturb AD progress are yet to be further explored given their
      complexities. In this review, we summarized recent progress regarding the GPCRs
      interacted with beta-site APP cleaving enzyme 1 (BACE1), a key secretase in AD
      pathogenesis. Then we discussed the current findings on the regulatory roles of
      GPCRs on BACE1, and the possibility for pharmaceutical treatment of AD patients
      by the allosteric modulators and biased ligands of GPCRs. We hope this review can
      provide new insights into the understanding of mechanistic link between GPCRs and
      BACE1, and highlight the potential of GPCRs as therapeutic target for AD. 

PMID- 27047377
TI  - Dynamic Progression of White Matter Hyperintensities in Alzheimer's Disease and
      Normal Aging: Results from the Sunnybrook Dementia Study.
AB  - Although white matter hyperintensities (WMH), markers of cerebral small vessel
      disease (SVD), are believed to generally increase over time, some studies have
      shown sharp decreases after therapeutic intervention, suggesting that WMH
      progression may be more dynamic than previously thought. Our primary goal was to
      examine dynamic progression of WMH in a real-world sample of Alzheimer's disease
      (AD) patients and normal elderly (NC), with varying degrees of SVD. WMH volumes
      from serial magnetic resonance imaging (MRI; mean = 1.8 years) were measured from
      NC (n = 44) and AD patients (n = 113) with high and low SVD burden. Dynamic
      progression for each individual was measured using spatial overlap images to
      assess shrinkage, growth, and stable WMH volumes. Significant group differences
      were found for shrinkage (p < 0.001), growth (p < 0.001) and stable (p < 0.001)
      WMH, where the AD high SVD group showed the largest changes relative to low SVD
      and NC. Our results suggest spatial progression measured at the individual
      patient level may be more sensitive to the dynamic nature of WMH. 

PMID- 27047378
TI  - Tinospora crispa (L.) Hook. f. & Thomson: A Review of Its Ethnobotanical,
      Phytochemical, and Pharmacological Aspects.
AB  - Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the
      rainforests or mixed deciduous forests in Asia and Africa, is used in traditional
      medicines to treat numerous health conditions. This review summarizes the up-to
      date reports about the ethnobotany, phytochemistry, pharmacological activities,
      toxicology, and clinical trials of the plant. It also provides critical
      assessment about the present knowledge of the plant which could contribute toward
      improving its prospect as a source of lead molecules for drug discovery. The
      plant has been used traditionally in the treatment of jaundice, rheumatism,
      urinary disorders, fever, malaria, diabetes, internal inflammation, fracture,
      scabies, hypertension, reducing thirst, increasing appetite, cooling down the
      body temperature, and maintaining good health. Phytochemical analyses of T.
      crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides,
      triterpenes, diterpenes and diterpene glycosides, cis clerodane-type
      furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed
      that the crude extracts and isolated compounds of T. crispa possessed a broad
      range of pharmacological activities such as anti-inflammatory, antioxidant,
      immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic
      activities. Most pharmacological studies were based on crude extracts of the
      plant and the bioactive compounds responsible for the bioactivities have not been
      well identified. Further investigations are required to transform the experience
      based claims on the use of T. crispa in traditional medicine practices into
      evidence-based information. The plant extract used in pharmacological and
      biological studies should be qualitatively and quantitatively analyzed based on
      its biomarkers. There should be detail in vitro and in vivo studies on the
      mechanisms of action of the pure bioactive compounds and more elaborate toxicity
      study to ensure safety of the plant for human use. More clinical trials are
      encouraged to be carried out if there are sufficient preclinical and safety data.

PMID- 27047379
TI  - Therapeutic Efficacy and Safety of Paeoniae Radix Rubra Formulae in Relieving
      Hyperbilirubinemia Induced by Viral Hepatitis: A Meta-Analysis.
AB  - OBJECTIVE: Hyperbilirubinemia is one of the most devastating pathologies induced
      by various liver diseases. Formulae related to Paeoniae Radix Rubra (PRR) at high
      doses have been applied to treat hyperbilirubinemia in traditional Chinese
      medicine (TCM). The aim of this systematic review and meta-analysis is to assess
      the efficacy and safety of formulae relevant to high-dose PRR in patients
      suffering from hyperbilirubinemia induced by viral hepatitis. METHODS: We
      performed a meta-analysis of randomized-controlled clinical trials to evaluate
      the efficacy and safety of formulae that apply a high dose of PRR for
      hyperbilirubinemia. Seven databases were searched until April, 2015. All studies
      were included according to detailed criteria and assessed for methodological
      quality. The outcome measurements were recorded for further analysis using the
      RevMan 5.2.11 software. RESULTS: Fifteen articles involving 1323 patients with
      hyperbilirubinemia were included. Formulae with high-dose PRR might promote the
      efficacy of either a combined application ([OR: 3.98, 95% CI (2.91, 5.43)]; P <
      0.01) or a single application ([OR: 4.00, 95% CI (1.50, 10.68)]; P < 0.01) for
      hyperbilirubinemia. The indices of TBIL, ALT, and AST significantly decreased
      ([MD: -75.57, 95% CI (-94.88, -56.26)], [MD: -26.54, 95% CI (-36.19, -16.88)],
      and ([MD: -28.94, 95% CI (-46.26, -11.61)]; P < 0.01), respectively. In addition,
      formulae with high-dose PRR could enhance the treatment efficacy of
      hyperbilirubinemia triggered by hepatitis B ([OR: 2.98, 95% CI (1.75, 5.05)]; P <
      0.01). Furthermore, the efficacy was enhanced with an increasing dosage of PRR.
      Two articles reported that no side effects occurred in clinical trials, and three
      studies noted that patients presented light digestive tract symptoms. CONCLUSION:
      Formulae relevant to high-dose PRR ameliorate hyperbilirubinemia and might
      constitute a promising therapeutic approach. For widespread acceptance by
      practitioners, more rigorously designed multicenter, double-blind, randomized,
      and large-scale controlled trials are required.

PMID- 27047381
TI  - Relationship between Statin Utilization and Socioeconomic Deprivation in Hungary.
AB  - The risk of premature mortality caused by cardiovascular diseases (CVDs) is
      approximately three times higher in the Central Eastern European region than in
      high income European countries, which suggests a lack and/or ineffectiveness of
      preventive interventions against CVDs. The aim of the present study was to
      provide data on the relationship between premature CVD mortality, statin
      utilization as a preventive medication and socioeconomic deprivation at the
      district level in Hungary. As a conceptually new approach, the prescription of
      statins, the prescription redemption and the ratio between redemption and
      prescription rates were also investigated. The number of prescriptions for
      statins and the number of redeemed statin prescriptions were obtained from the
      National Health Insurance Fund Administration of Hungary for each primary
      healthcare practice for the entire year of 2012. The data were aggregated at the
      district level. To define the frequency of prescription and of redemption, the
      denominator was the number of the 40+-year-old population adjusted by the rates
      of 60+-year-old population of the district. The standardized mortality rates,
      frequency of statin prescriptions, redeemed statin prescriptions, and ratios for
      compliance in relation to the national average were mapped using the "disease
      mapping" option, and their association with deprivation (tertile of deprivation
      index as a district-based categorical covariate) was defined using the risk
      analysis capabilities within the Rapid Inquiry Facility. The risk analysis showed
      a significant positive association between deprivation and the relative risk of
      premature cardiovascular mortality, and a reverse J-shaped association between
      the relative frequency of statin prescriptions and deprivation. Districts with
      the highest deprivation showed a low relative frequency of statin prescriptions;
      however, significantly higher primary compliance (redemption) was observed in
      districts with the highest deprivation. Our data clearly indicate that
      insufficient statin utilization is strongly linked to the so-called physician
      factor, i.e., a statin prescription. Consequently, statin treatment is poor and
      represents a significant barrier to reducing mortality, particularly among people
      living in highly deprived areas of the country. 

PMID- 27047382
TI  - Antrodia camphorata Increases Insulin Secretion and Protects from Apoptosis in
      MIN6 Cells.
AB  - Antrodia camphorata is a Taiwanese-specific fungus which has been used clinically
      to treat hypertension, immune- and liver-related diseases and cancer; however, it
      has never been studied in type 2 diabetes mellitus (T2DM). Hyperglycemia in T2DM
      causes endoplasmic reticulum (ER) stress, leading to beta-cell dysfunction.
      During chronic ER stress, misfolded proteins accumulate and initiate beta-cell
      apoptosis. Moreover, beta-cell dysfunction leads to defect in insulin secretion,
      which is the key process in the development and progression of T2DM. Therefore,
      the aim of the present study was to examine the effects of A. camphorata on
      insulin secretion and ER stress-induced apoptosis in a mouse beta-cell line,
      MIN6, and their underlying mechanisms. We demonstrated that the ethanolic extract
      of A. camphorata increased glucose-induced insulin secretion dose-dependently
      through peroxisome proliferator-activated receptor-gamma (PPAR-gamma) pathway,
      and upregulated genes that were involved in insulin secretion, including PPAR
      gamma, glucose transporter-2 and glucokinase. Furthermore, A. camphorata slightly
      increased cell proliferation, as well as protected from ER stress-induced
      apoptosis in MIN6 cells. In conclusion, this study provided evidences that A.
      camphorata might have anti-diabetic effects and could be a novel drug for T2DM. 

PMID- 27047383
TI  - Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced
      Colitis.
AB  - BACKGROUND AND AIMS: Changes in gut serotonin (5-HT) content have been described
      in Inflammatory Bowel Disease (IBD) and in different experimental models of
      colitis: the critical role of this monoamine in the pathogenesis of chronic
      gastrointestinal inflammation is gradually emerging. Aim of the present study was
      to evaluate the contribution of endogenous 5-HT through the activation of its
      specific receptor subtypes to the local and systemic inflammatory responses in an
      experimental model of IBD. MATERIALS AND METHODS: Colitis was induced by
      intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with
      selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT3
      (Ondansetron), 5-HT4 (GR125487), 5-HT7 (SB269970) receptors and with 5-HT1A
      agonist 8-Hydroxy-2-(di-n-propylamino)tetralin. RESULTS: Blockade of 5-HT1A
      receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5
      HT1A agonist delayed and mitigated the severity of colitis, counteracting the
      increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors
      improved global health conditions, reduced colonic morphological alterations,
      down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic
      apoptosis. Antagonism of 5-HT3, 5-HT4, and 5-HT7 receptor sites did not
      remarkably affect the progression and outcome of the pathology or only slightly
      improved it. CONCLUSION: The prevailing deleterious contribution given by
      endogenous 5-HT to inflammation in TNBS-induced colitis is seemingly mediated by
      5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak
      beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only
      a selective interference with 5-HT pro-inflammatory actions may represent an
      additional potential therapeutic option for intestinal inflammatory disorders.

PMID- 27047380
TI  - Quinoxaline 1,4-di-N-Oxides: Biological Activities and Mechanisms of Actions.
AB  - Quinoxaline 1,4-di-N-oxides (QdNOs) have manifold biological properties,
      including antimicrobial, antitumoral, antitrypanosomal and
      antiinflammatory/antioxidant activities. These diverse activities endow them
      broad applications and prospects in human and veterinary medicines. As QdNOs
      arouse widespread interest, the evaluation of their medicinal chemistry is still
      in progress. In the meantime, adverse effects have been reported in some of the
      QdNO derivatives. For example, genotoxicity and bacterial resistance have been
      found in QdNO antibacterial growth promoters, conferring urgent need for
      discovery of new QdNO drugs. However, the modes of actions of QdNOs are not fully
      understood, hindering the development and innovation of these promising
      compounds. Here, QdNOs are categorized based on the activities and usages, among
      which the antimicrobial activities are consist of antibacterial,
      antimycobacterial and anticandida activities, and the antiprotozoal activities
      include antitrypanosomal, antimalarial, antitrichomonas, and antiamoebic
      activities. The structure-activity relationship and the mode of actions of each
      type of activity of QdNOs are summarized, and the toxicity and the underlying
      mechanisms are also discussed, providing insight for the future research and
      development of these fascinating compounds. 

PMID- 27047384
TI  - An Analytical Framework for Studying Small-Number Effects in Catalytic Reaction
      Networks: A Probability Generating Function Approach to Chemical Master
      Equations.
AB  - Cell activities primarily depend on chemical reactions, especially those mediated
      by enzymes, and this has led to these activities being modeled as catalytic
      reaction networks. Although deterministic ordinary differential equations of
      concentrations (rate equations) have been widely used for modeling purposes in
      the field of systems biology, it has been pointed out that these catalytic
      reaction networks may behave in a way that is qualitatively different from such
      deterministic representation when the number of molecules for certain chemical
      species in the system is small. Apart from this, representing these phenomena by
      simple binary (on/off) systems that omit the quantities would also not be
      feasible. As recent experiments have revealed the existence of rare chemical
      species in cells, the importance of being able to model potential small-number
      phenomena is being recognized. However, most preceding studies were based on
      numerical simulations, and theoretical frameworks to analyze these phenomena have
      not been sufficiently developed. Motivated by the small-number issue, this work
      aimed to develop an analytical framework for the chemical master equation
      describing the distributional behavior of catalytic reaction networks. For
      simplicity, we considered networks consisting of two-body catalytic reactions. We
      used the probability generating function method to obtain the steady-state
      solutions of the chemical master equation without specifying the parameters. We
      obtained the time evolution equations of the first- and second-order moments of
      concentrations, and the steady-state analytical solution of the chemical master
      equation under certain conditions. These results led to the rank conservation
      law, the connecting state to the winner-takes-all state, and analysis of 2
      molecules M-species systems. A possible interpretation of the theoretical
      conclusion for actual biochemical pathways is also discussed. 

PMID- 27047386
TI  - Transcriptome Analysis of Differentially Expressed Genes Involved in
      Proanthocyanidin Accumulation in the Rhizomes of Fagopyrum dibotrys and an
      Irradiation-Induced Mutant.
AB  - The rhizome of Fagopyrum dibotrys is a traditional Chinese medicine that has
      recently gained attention due to substantial findings regarding its bioactive
      proanthocyanidin (PA) compounds. However, the molecular mechanism underlying PA
      accumulation in F. dibotrys remains elusive. We previously obtained an
      irradiation-induced mutant (RM_R) of F. dibotrys that had a higher PA content
      compared to that of the wild-type (CK_R). The present study aimed to elucidate
      the molecular mechanism underlying PA accumulation in F. dibotrys by comparing
      the rhizome transcriptomes of the irradiation-induced mutant and wild-type using
      RNA-seq analysis. A total of 53,540 unigenes were obtained, of which 29,901
      (55.84%) were annotated based on BLAST searches against public databases, and 501
      unique sequences were differentially expressed between the two samples, which
      consisted of 204 up-regulated and 297 down-regulated unigenes. Further analysis
      showed that the expression patterns of some unigenes encoding enzymes involved in
      PAs biosynthesis in F. dibotrys rhizomes differed between RM_R and CK_R. In
      addition, we identified transcription factor families and several cytochrome
      P450s that may be involved in PA regulation in F. dibotrys. Finally, 12 unigenes
      that encode PA biosynthetic enzymes were confirmed by qRT-PCR analysis. This
      study sheds light on the molecular mechanism underlying radiation-mediated
      flavonoid accumulation and regulation in F. dibotrys rhizomes. These results will
      also provide a platform for further functional genomic research on this
      particular species. 

PMID- 27047385
TI  - Role of Extracellular Vesicles and microRNAs on Dysfunctional Angiogenesis during
      Preeclamptic Pregnancies.
AB  - Preeclampsia is a syndrome characterized by hypertension during pregnancy, which
      is a leading cause of morbidity and mortality in both mother and newborn in
      developing countries. Some advances have increased the understanding of
      pathophysiology of this disease. For example, reduced utero-placental blood flow
      associated with impaired trophoblast invasion may lead to a hypoxic placenta that
      releases harmful materials into the maternal and feto-placental circulation and
      impairs endothelial function. Identification of these harmful materials is one of
      the hot topics in the literature, since these provide potential biomarkers.
      Certainty, such knowledge will help us to understand the miscommunication between
      mother and fetus. In this review we highlight how placental extracellular
      vesicles and their cargo, such as small RNAs (i.e., microRNAs), might be involved
      in endothelial dysfunction, and then in the angiogenesis process, during
      preeclampsia. Currently only a few reports have addressed the potential role of
      endothelial regulatory miRNA in the impaired angiogenesis in preeclampsia. One of
      the main limitations in this area is the variability of the analyses performed in
      the current literature. This includes variability in the size of the particles
      analyzed, and broad variation in the exosomes considered. The quantity of
      microRNA targets genes suggest that practically all endothelial cell metabolic
      functions might be impaired. More studies are required to investigate mechanisms
      underlying miRNA released from placenta upon endothelial function involved in the
      angiogenenic process. 

PMID- 27047387
TI  - The Importance of Monitoring Sleep within Adolescent Athletes: Athletic,
      Academic, and Health Considerations.

PMID- 27047388
TI  - Similar Responses of Circulating MicroRNAs to Acute High-Intensity Interval
      Exercise and Vigorous-Intensity Continuous Exercise.
AB  - High-intensity interval exercise (HIIE) has been reported to be more beneficial
      for physical adaptation than low-to-moderate exercise intensity. Recently, it is
      becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish
      between specific stress signals imposed by variations in the duration, modality,
      and type of exercise. The aim of this study is to investigate whether or not HIIE
      is superior to vigorous-intensity continuous exercise (VICE), which is
      contributing to develop effective fitness assessment. Twenty-six young males were
      enrolled, and plasma samples were collected prior to exercise and immediately
      after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were
      initially determined using TaqMan Low Density Array (TLDA). And the
      differentially miRNAs levels were validated by stem-loop quantitative reverse
      transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured
      for VICE. Our results showed that some muscle-related miRNAs levels in the
      plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased
      following HIIE or VICE compared to those at rest (P < 0.05), and there was only a
      significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while
      no significant differences were observed for other muscle-related miRNAs between
      both exercises (P > 0.05). In addition, some tissue-related or unknown original
      miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR
      522, miR-553, and miR-888, also significantly increased (P < 0.05) in both
      exercises compared to rest. However, no significant differences were found
      between both exercises (P > 0.05). Overall, endurance exercise assessed in this
      study both led to significant increases in selective c-miRNAs of comparable
      magnitude, suggesting that both types of endurance exercise have general stress
      processes. Accordingly, the similar responses to both acute exercises likely
      indicate both exercises can be used interchangeably. Further work is needed to
      reveal the functional significance and signaling mechanisms behind changes in c
      miRNA turnover during exercise. 

PMID- 27047389
TI  - Acute Aerobic Swimming Exercise Induces Distinct Effects in the Contractile
      Reactivity of Rat Ileum to KCl and Carbachol.
AB  - Aerobic exercise promotes short-term physiological changes in the intestinal
      smooth muscle associated to the ischemia-reperfusion process; however, few
      studies have demonstrated its effect on the intestinal contractile function.
      Thus, this work describes our observations regarding the influence of acute
      aerobic swimming exercise in the contractile reactivity, oxidative stress, and
      morphology of rat ileum. Wistar rats were divided into sedentary (SED) and
      acutely exercised (EX-AC) groups. Animals were acclimated by 10, 10, and 30 min
      of swimming exercise in intercalated days 1 week before exercise. Then they were
      submitted to forced swimming for 1 h with a metal of 3% of their body weight
      attached to their body. Animals were euthanized immediately after the exercise
      section and the ileum was suspended in organ baths for monitoring isotonic
      contractions. The analysis of lipid peroxidation was performed in order to
      determinate the malondialdehyde (MDA) levels as a marker of oxidative stress, and
      intestinal smooth muscle morphology by histological staining. Cumulative
      concentration-response curves to KCl were altered in the EX-AC with an increase
      in both its efficacy and potency (E max = 153.2 +/- 2.8%, EC 50 = 1.3 +/- 0.1 *
      10(-2) M) compared to the SED group (E max = 100%, EC 50 = 1.8 +/- 0.1 * 10(-2)
      M). Interestingly, carbachol had its efficacy and potency reduced in the EX-AC (E
      max = 67.1 +/- 1.4%, EC 50 = 9.8 +/- 1.4 * 10(-7) M) compared to the SED group (E
      max = 100%, EC 50 = 2.0 +/- 0.2 * 10(-7) M). The exercise did not alter the MDA
      levels in the ileum (5.4 +/- 0.6 MU mol/mL) in the EX-AC compared to the SED
      group (8.4 +/- 1.7 MU mol/mL). Moreover, neither the circular nor the
      longitudinal smooth muscle layers thickness were modified by the exercise (66.2
      +/- 6.0 and 40.2 +/- 2.6 MUm, respectively), compared to the SED group (61.6 +/-
      6.4 and 34.8 +/- 3.7 MUm, respectively). Therefore, the ileum sensitivity to
      contractile agents is differentially altered by the acute aerobic swimming
      exercise, without affecting the oxidative stress and the morphology of ileum
      smooth muscle. 

PMID- 27047390
TI  - Rapamycin Inhibits Cardiac Hypertrophy by Promoting Autophagy via the
      MEK/ERK/Beclin-1 Pathway.
AB  - Rapamycin, also known as sirolimus, is an antifungal agent and immunosuppressant
      drug used to prevent organ rejection in transplantation. However, little is known
      about the role of rapamycin in cardiac hypertrophy and the signaling pathways
      involved. Here, the effect of rapamycin was examined using phenylephrine (PE)
      induced cardiomyocyte hypertrophy in vitro and in a rat model of aortic banding
      (AB) - induced hypertrophy in vivo. Inhibition of MEK/ERK signaling reversed the
      effect of rapamycin on the up-regulation of LC3-II, Beclin-1 and Noxa, and the
      down-regulation of Mcl-1 and p62. Silencing of Noxa or Beclin-1 suppressed
      rapamycin-induced autophagy, and co-immunoprecipitation experiments showed that
      Noxa abolishes the inhibitory effect of Mcl-1 on Beclin-1, promoting autophagy.
      In vivo experiments showed that rapamycin decreased AB-induced cardiac
      hypertrophy in a MEK/ERK dependent manner. Taken together, our results indicate
      that rapamycin attenuates cardiac hypertrophy by promoting autophagy through a
      mechanism involving the modulation of Noxa and Beclin-1 expression by the MEK/ERK
      signaling pathway. 

PMID- 27047391
TI  - Corrigendum: Protective effects of intermittent hypoxia on brain and memory in a
      mouse model of apnea of prematurity.
AB  - [This corrects the article on p. 313 in vol. 6, PMID: 26582992.]. 

PMID- 27047392
TI  - Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway.
AB  - Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly
      influenced by factors circulating in blood. We have shown that the hormone
      ouabain enhances several characteristics of the ADPKD cystic phenotype, including
      the rate of cell proliferation, fluid secretion and the capacity of the cells to
      form cysts. In this work, we found that physiological levels of ouabain (3 nM)
      also promote programmed cell death of renal epithelial cells obtained from kidney
      cysts of patients with ADPKD (ADPKD cells). This was determined by Alexa Fluor
      488 labeled-Annexin-V staining and TUNEL assay, both biochemical markers of
      apoptosis. Ouabain-induced apoptosis also takes place when ADPKD cell growth is
      blocked; suggesting that the effect is not secondary to the stimulatory actions
      of ouabain on cell proliferation. Ouabain alters the expression of BCL family of
      proteins, reducing BCL-2 and increasing BAX expression levels, anti- and pro
      apoptotic mediators respectively. In addition, ouabain caused the release of
      cytochrome c from mitochondria. Moreover, ouabain activates caspase-3, a key
      "executioner" caspase in the cell apoptotic pathway, but did not affect caspase
      8. This suggests that ouabain triggers ADPKD cell apoptosis by stimulating the
      intrinsic, but not the extrinsic pathway of programmed cell death. The apoptotic
      effects of ouabain are specific for ADPKD cells and do not occur in normal human
      kidney cells (NHK cells). Taken together with our previous observations, these
      results show that ouabain causes an imbalance in cell growth/death, to favor
      growth of the cystic cells. This event, characteristic of ADPKD, further suggests
      the importance of ouabain as a circulating factor that promotes ADPKD
      progression. 

PMID- 27047393
TI  - Reduced Dietary Sodium Intake Increases Heart Rate. A Meta-Analysis of 63
      Randomized Controlled Trials Including 72 Study Populations.
AB  - Reduced dietary sodium intake (sodium reduction) increases heart rate in some
      studies of animals and humans. As heart rate is independently associated with the
      development of heart failure and increased risk of premature death a potential
      increase in heart rate could be a harmful side-effect of sodium reduction. The
      purpose of the present meta-analysis was to investigate the effect of sodium
      reduction on heart rate. Relevant studies were retrieved from an updated pool of
      176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty
      three of the RCTs including 72 study populations reported data on heart rate. In
      a meta-analysis of these data sodium reduction increased heart rate with 1.65
      beats per minute [95% CI: 1.19, 2.11], p < 0.00001, corresponding to 2.4% of the
      baseline heart rate. This effect was independent of baseline blood pressure. In
      conclusion sodium reduction increases heart rate by as much (2.4%) as it
      decreases blood pressure (2.5%). This side-effect, which may cause harmful health
      effects, contributes to the need for a revision of the present dietary
      guidelines. 

PMID- 27047394
TI  - Effects of Sulpiride on True and False Memories of Thematically Related Pictures
      and Associated Words in Healthy Volunteers.
AB  - Episodic memory, working memory, emotional memory, and attention are subject to
      dopaminergic modulation. However, the potential role of dopamine on the
      generation of false memories is unknown. This study defined the role of the
      dopamine D2 receptor on true and false recognition memories. Twenty-four young,
      healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a
      dopamine D2-receptor antagonist, just before starting the recognition memory task
      in a randomized, double-blind, and placebo-controlled trial. The sulpiride group
      presented more false recognitions during visual and verbal processing than the
      placebo group, although both groups had the same indices of true memory. These
      findings demonstrate that dopamine D2 receptors blockade in healthy volunteers
      can specifically increase the rate of false recognitions. The findings fit well
      the two-process view of causes of false memories, the activation/monitoring
      failures model. 

PMID- 27047395
TI  - Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory
      Dysfunctions in Patients with Schizophrenia.
AB  - Patients with schizophrenia show abnormal dynamics and structure of temporally 
      coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in
      preparation for a cognitively demanding task. During working memory (WM) tasks,
      patients with schizophrenia show persistent deficits in TCNs as well as EEG
      indices of WM. Studying their temporal relationship during WM tasks might provide
      novel insights into WM performance deficits seen in schizophrenia. Simultaneous
      EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task
      with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17
      matched healthy controls. Using covariance mapping, we investigated the
      relationship of the activity in the TCNs before the memoranda were encoded and
      EEG spectral power during the retention interval. We assessed four TCNs - default
      mode network (DMN), dorsal attention network (dAN), left and right working memory
      networks (WMNs) - and three EEG bands - theta, alpha, and beta. In healthy
      controls, there was a load-dependent inverse relation between DMN and frontal
      midline theta power and an anti-correlation between DMN and dAN. Both effects
      were not significantly detectable in patients. In addition, healthy controls
      showed a left-lateralized load-dependent recruitment of the WMNs. Activation of
      the WMNs was bilateral in patients, suggesting more resources were recruited for
      successful performance on the WM task. Our findings support the notion of
      schizophrenia patients showing deviations in their neurophysiological responses
      before the retention of relevant information in a verbal WM task. Thus, treatment
      strategies as neurofeedback -targeting prestates could be beneficial as task
      performance relies on the preparatory state of the brain. 

PMID- 27047396
TI  - Depression and the Link with Cardiovascular Disease.
AB  - This review provides an outline of the association between major depressive
      disorder (MDD) and coronary heart disease (CHD). Much is known about the two
      individual clinical conditions; however, it is not until recently, biological
      mechanisms have been uncovered that link both MDD and CHD. The activation of
      stress pathways have been implicated as a neurochemical mechanism that links MDD
      and CHD. Depression is known to be associated with poorer outcomes of CHD.
      Psychological factors, such as major depression and stress, are now known as risk
      factors for developing CHD, which is as important and is independent of classic
      risk factors, such as hypertension, diabetes mellitus, and cigarette smoking.
      Both conditions have great socioeconomic importance given that depression and CHD
      are likely to be two of the three leading causes of global burden of disease.
      Better understanding of the common causal pathways will help us delineate more
      appropriate treatments. 

PMID- 27047397
TI  - DNA Methylation at the Neonatal State and at the Time of Diagnosis: Preliminary
      Support for an Association with the Estrogen Receptor 1, Gamma-Aminobutyric Acid
      B Receptor 1, and Myelin Oligodendrocyte Glycoprotein in Female Adolescent
      Patients with OCD.
AB  - Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Non-genetic
      factors and their interaction with genes have attracted increasing attention.
      Epigenetics is regarded an important interface between environmental signals and
      activation/repression of genomic responses. Epigenetic mechanisms have not
      previously been examined in OCD in children and adolescents. The aim of the
      present study was to examine the DNA methylation profile of selected genes in
      blood spots from neonates later diagnosed with OCD and in the same
      children/adolescents at the time of diagnosis compared with age- and sex-matched
      controls. Furthermore, we wanted to characterize the association of the
      differential methylation profiles with the severity of OCD and treatment outcome.
      Dried and new blood spot samples were obtained from 21 female
      children/adolescents with verified OCD and 12 female controls. The differential
      methylation was analyzed using a linear model and the correlation with the
      severity of OCD and treatment outcome was analyzed using the Pearson correlation.
      We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes
      within and up to 100,000 bp up- and downstream of 14 genes previously associated
      with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3,
      ESR1, SL6A4, TPH2, and COMT). The study found no significantly differential
      methylation. However, preliminary support for a difference was found for the
      gamma-aminobutyric acid (GABA) B receptor 1 (cg10234998, cg17099072) in blood
      samples at birth and for the estrogen receptor 1 (ESR1) (cg10939667), the myelin
      oligodendrocyte glycoprotein (MOG) (cg16650906), and the brain-derived
      neurotrophic factor (BDNF) (cg14080521) in blood samples at the time of
      diagnosis. Preliminary support for an association was observed between the
      methylation profiles of GABBR1 and MOG and baseline severity, treatment effect,
      and responder status; and between the methylation profile of ESR1 and baseline
      severity. To our knowledge, this is the first study to examine the DNA
      methylation profiles in OCD. The study points towards possible differences in the
      methylation profiles and suggests a correlation with the severity of OCD.
      However, the results warrant further studies in larger sample sets. 

PMID- 27047398
TI  - Meditative Movement as a Treatment for Pulmonary Dysfunction in Flight Attendants
      Exposed to Second-Hand Cigarette Smoke: Study Protocol for a Randomized Trial.
AB  - A study protocol is presented for the investigation of meditative movement (MM)
      as a treatment for pulmonary dysfunction in flight attendants (FA) who were
      exposed to second-hand cigarette smoke while flying before the smoking ban. The
      study will have three parts, some of which will run concurrently. The first is a
      data gathering and screening phase, which will gather data on pulmonary and other
      aspects of the health of FA, and will also serve to screen participants for the
      other phases. Second is an exercise selection phase, in which a variety of MM
      exercises will be taught, over a 16-week period, to a cohort of 20 FA. A subset
      of these exercises will be selected on the basis of participant feedback on
      effectiveness and compliance. Third is a 52-week randomized controlled trial to
      evaluate the effectiveness of a digitally delivered form of the previously
      selected exercises on a group of 20 FA, as compared with an attention control
      group. Outcome measures to be used in all three parts of the study include the 6
      min walk test as a primary measure, as well as a range of biomarkers, tests, and
      questionnaires documenting hormonal, cardio-respiratory, autonomic, and affective
      state. This study is registered at ClinicalTrials.gov. Identifier: NCT02612389. 

PMID- 27047399
TI  - Chronic Cervicogenic Tinnitus Rapidly Resolved by Intermittent Use of Cervical
      Collar.
AB  - INTRODUCTION: Cervicogenic tinnitus is not a generally accepted pathogenetic
      subtype, which might be subsumed under the concept of somatosensory tinnitus.
      After the personal experience of therapy-resistant tinnitus in context with a
      cervical pain syndrome (CPS) and successful add-on treatment with cervical collar
      (CC), the idea was pursued in several individual treatments in patients. PATIENTS
      AND METHODS: Reporting one particular case with chronic tinnitus, considered
      untreatable, that rapidly improved with exclusive treatment by CC use.
      Thereafter, tinnitus was experimentally replicated by head inclination, the
      respective neck-head angles, and cerebral blood flow was measured. RESULTS:
      Chronic subjective tinnitus of a 20 years duration completely disappeared within
      4 weeks with an intermittent short time application of CC. Thereafter, tinnitus
      was deliberately again induced by head inclination, set on with anterior tilt of
      14 degrees , reaching maximum strength by 23 degrees . Tinnitus stopped with
      return to neutral head position. Blood flow in the vertebral arteries on both
      sides was unchanged during head inclination with prevalent tinnitus; however,
      blood flow was physiologically reduced with head rotation though not accompanied
      by tinnitus. DISCUSSION: In a single case of chronic tinnitus, we found that
      treatment with CC rapidly led to full remission. Blood flow reduction in
      vertebral arteries was unrelated to tinnitus. However, tinnitus could be resumed
      by constrained head postures. Experimental tinnitus replication (by inclination)
      points to an underscored role of upper posterior cervical muscle groups, matching
      with animal experiments, also in concert with other triggers including
      psychological factors.

PMID- 27047400
TI  - A Closer Look at the Effects of Repeated Cocaine Exposure on Adaptive Decision
      Making under Conditions That Promote Goal-Directed Control.
AB  - It has been proposed that compulsive drug seeking reflects an underlying
      dysregulation in adaptive behavior that favors habitual (automatic and
      inflexible) over goal-directed (deliberative and highly flexible) action
      selection. Rodent studies have established that repeated exposure to cocaine or
      amphetamine facilitates the development of habits, producing behavior that
      becomes unusually insensitive to a reduction in the value of its outcome. The
      current study more directly investigated the effects of cocaine pre-exposure on
      goal-directed learning and action selection using an approach that discourages
      habitual performance. After undergoing a 15-day series of cocaine (15 or 30
      mg/kg, i.p.) or saline injections and a drug withdrawal period, rats were trained
      to perform two different lever-press actions for distinct reward options. During
      a subsequent outcome devaluation test, both cocaine- and saline-treated rats
      showed a robust bias in their choice between the two actions, preferring
      whichever action had been trained with the reward that retained its value. Thus,
      it appears that the tendency for repeated cocaine exposure to promote habit
      formation does not extend to a more complex behavioral scenario that encourages
      goal-directed control. To further explore this issue, we assessed how prior
      cocaine treatment would affect the rats' ability to learn about a selective
      reduction in the predictive relationship between one of the two actions and its
      outcome, which is another fundamental feature of goal-directed behavior.
      Interestingly, we found that cocaine-treated rats showed enhanced, rather than
      diminished, sensitivity to this action-outcome contingency degradation
      manipulation. Given their mutual dependence on striatal dopamine signaling, we
      suggest that cocaine's effects on habit formation and contingency learning may
      stem from a common adaptation in this neurochemical system. 

PMID- 27047401
TI  - The Cognitive Deficits Associated with Second-Hand Smoking.

PMID- 27047402
TI  - Priming Children's Use of Intentions in Moral Judgement with Metacognitive
      Training.
AB  - Typically, adults give a primary role to the agent's intention to harm when
      performing a moral judgment of accidental harm. By contrast, children often focus
      on outcomes, underestimating the actor's mental states when judging someone for
      his action, and rely on what we suppose to be intuitive and emotional processes.
      The present study explored the processes involved in the development of the
      capacity to integrate agents' intentions into their moral judgment of accidental
      harm in 5 to 8-year-old children. This was done by the use of different
      metacognitive trainings reinforcing different abilities involved in moral
      judgments (mentalising abilities, executive abilities, or no reinforcement),
      similar to a paradigm previously used in the field of deductive logic. Children's
      moral judgments were gathered before and after the training with non-verbal
      cartoons depicting agents whose actions differed only based on their causal role
      or their intention to harm. We demonstrated that a metacognitive training could
      induce an important shift in children's moral abilities, showing that only
      children who were explicitly instructed to "not focus too much" on the
      consequences of accidental harm, preferentially weighted the agents' intentions
      in their moral judgments. Our findings confirm that children between the ages of
      5 and 8 are sensitive to the intention of agents, however, at that age, this
      ability is insufficient in order to give a "mature" moral judgment. Our
      experiment is the first that suggests the critical role of inhibitory resources
      in processing accidental harm. 

PMID- 27047403
TI  - Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia.
AB  - The cerebellar deficit hypothesis for developmental dyslexia claims that
      cerebellar dysfunction causes the failures in the acquisition of visuomotor
      skills and automatic reading and writing skills. In people with dyslexia in the
      alphabetic languages, the abnormal activation and structure of the right or
      bilateral cerebellar lobes have been identified. Using a typical implicit motor
      learning task, however, one neuroimaging study demonstrated the left cerebellar
      dysfunction in Chinese children with dyslexia. In the present study, using voxel
      based morphometry, we found decreased gray matter volume in the left cerebellum
      in Chinese children with dyslexia relative to age-matched controls. The positive
      correlation between reading performance and regional gray matter volume suggests
      that the abnormal structure in the left cerebellum is responsible for reading
      disability in Chinese children with dyslexia. 

PMID- 27047404
TI  - Impact of Not Addressing Partially Cross-Classified Multilevel Structure in
      Testing Measurement Invariance: A Monte Carlo Study.
AB  - In educational settings, researchers are likely to encounter multilevel data with
      cross-classified structure. However, due to the lack of familiarity and
      limitations of statistical software for cross-classified modeling, most
      researchers adopt less optimal approaches to analyze cross-classified multilevel
      data in testing measurement invariance. We conducted two Monte Carlo studies to
      investigate the performances of testing measurement invariance with cross
      classified multilevel data when the noninvarinace is at the between-level: (a)
      the impact of ignoring crossed factor using conventional multilevel confirmatory
      factor analysis (MCFA) which assumes hierarchical multilevel data in testing
      measurement invariance and (b) the adequacy of the cross-classified multiple
      indicators multiple causes (MIMIC) models with cross-classified data. We
      considered two design factors, intraclass correlation (ICC) and magnitude of non
      invariance. Generally, MCFA demonstrated very low statistical power to detect non
      invariance. The low power was plausibly related to the underestimated factor
      loading differences and the underestimated ICC due to the redistribution of the
      variance component from the ignored crossed factor. The results demonstrated
      possible incorrect statistical inferences with conventional MCFA analyses that
      assume multilevel data as hierarchical structure for testing measurement
      invariance with cross-classified data (non-hierarchical structure). On the
      contrary, the cross-classified MIMIC model demonstrated acceptable performance
      with cross-classified data. 

PMID- 27047406
TI  - From Decent Work to Decent Lives: Positive Self and Relational Management (PS&RM)
      in the Twenty-First Century.
AB  - The aim of the present study is to empirically test the theoretical model,
      Positive Self and Relational Management (PS&RM), for a sample of 184 Italian
      university students. The PS&RM model specifies the development of individuals'
      strengths, potentials, and talents across the lifespan and with regard to the
      dialect of self in relationship. PS&RM is defined theoretically by three
      constructs: Positive Lifelong Life Management, Positive Lifelong Self-Management,
      Positive Lifelong Relational Management. The three constructs are operationalized
      as follows: Positive Lifelong Life Management is measured by the Positive and
      Negative Affect Schedule (PANAS), the Satisfaction With Life Scale (SWLS), the
      Meaningful Life Measure (MLM), and the Authenticity Scale (AS); Positive Lifelong
      Self-Management is measured by the Intrapreneurial Self-Capital Scale (ISC), the
      Career Adapt-Abilities Scale (CAAS), and the Life Project Reflexivity Scale
      (LPRS); and Positive Lifelong Relational Management is measured by the Trait
      Emotional Intelligence Questionnaire (TEIQue), the Multidimensional Scale for
      Perceived Social Support (MSPSS), and the Positive Relational Management Scale
      (PRMS). Confirmatory factor analysis of the PS&RM model was completed using
      structural equation modeling. The theoretical PS&RM model was empirically tested
      as defined by the three hypothesized constructs. Empirical support for this model
      offers a framework for further research and the design of preventive
      interventions to promote decent work and decent lives in the twenty-first
      century. 

PMID- 27047405
TI  - Depression and Inflammatory Periodontal Disease Considerations-An
      Interdisciplinary Approach.

PMID- 27047407
TI  - Operationalizing Heedful Interrelating: How Attending, Responding, and Feeling
      Comprise Coordinating and Predict Performance in Self-Managing Teams.
AB  - Team coordination implies a system of individual behavioral contributions
      occurring within a network of interpersonal relationships to achieve a collective
      goal. Current research on coordination has emphasized its relational aspects, but
      has not adequately accounted for how team members also simultaneously manage
      individual behavioral contributions and represent the whole system of the team's
      work. In the current study, we develop theory and test how individuals manage all
      three aspects of coordinating through the three facets described in the theory of
      heedful interrelating. We operationalize the facet of contributing as
      distributing attention between self and others, subordinating as responsively
      communicating, and representing as feeling the system of the team's work as a
      cohesive whole. We then test the relationships among these facets and their
      influence on team performance in an experiment with 50 ad hoc triads of
      undergraduate student self-managing teams tasked with collectively composing a
      song in the lab. In analyzing thin-slices of video data of these teams'
      coordination, we found that teams with members displaying greater dispersion of
      attentional distribution and more responsive communicating experienced a stronger
      feeling of the team as a whole. Responsive communication also predicted team
      performance. Accounting for how the three aspects of coordinating are managed by
      individual team members provides a more critical understanding of heedful
      interrelating, and insight into emergent coordination processes. 

PMID- 27047408
TI  - Enabling Delay of Gratification Behavior in Those Not So Predisposed: The
      Moderating Role of Social Support.
AB  - The presence of delay of gratification (DG) in childhood is correlated with
      success later in a person's life. Is there any way of helping adults with a low
      level of DG to obtain similar success? The present research examines how social
      support helps those low in DG nonetheless to act similarly to those high in DG.
      This research includes both correlational studies and experiments that manipulate
      social support as well as both field studies and a laboratory study. The results
      show that with high social support, employees (Study 1) and university students
      (Study 2) low in DG report vocational and academic DG behavioral intentions,
      respectively, similar to those high in DG. Study 3 found that participants low in
      DG who were primed with high social support expressed job-choice DG similar to
      those high in the DG. Study 4 controlled for mood and self-image and found that
      participants low in DG who were primed with high social support expressed more
      money-choice DG than those high in the DG. Study 5 showed that social support
      moderated the relationship between DG and actual DG behaviors. These findings
      provide evidence for a moderating role of social support in the expression of DG
      behavior. 

PMID- 27047409
TI  - The Mad Genius Stereotype: Still Alive and Well.
AB  - Scientists and laypeople agree on high ability as a defining feature of
      giftedness. Yet their views on gifted people's socioemotional characteristics
      diverge. Most studies find the gifted to be similar or slightly superior to
      average-ability persons in these domains ("harmony hypothesis"). However,
      subjective conceptions and media representations, most of which have focused on
      gifted children and youth, stress the socioemotional downsides of giftedness
      ("disharmony hypothesis"), affecting highly able individuals and those around
      them, thus hampering individual development. To date, most studies on gifted
      stereotypes have examined selective samples, mostly teachers. The present study
      is the first to provide representative data on conceptions of gifted individuals
      in general. A brief survey of 1029 German adults assessed quality and prevalence
      of stereotypes about gifted individuals, without an explicit focus on children
      and/or adolescents. Latent class analysis (LCA) revealed two conceptions of
      giftedness, with twice as many "disharmonious" than "harmonious" raters. Male
      gender, single parenthood, unemployment, higher income or negative attitudes
      toward the gifted predicted disharmonious ratings. However, effects were small,
      suggesting future studies look deeper into the processes of stereotype formation
      and maintenance. 

PMID- 27047410
TI  - The Social Perception of Heroes and Murderers: Effects of Gender-Inclusive
      Language in Media Reports.
AB  - The way media depict women and men can reinforce or diminish gender stereotyping.
      Which part does language play in this context? Are roles perceived as more gender
      balanced when feminine role nouns are used in addition to masculine ones?
      Research on gender-inclusive language shows that the use of feminine-masculine
      word pairs tends to increase the visibility of women in various social roles. For
      example, when speakers of German were asked to name their favorite "heroine or
      hero in a novel," they listed more female characters than when asked to name
      their favorite "hero in a novel." The research reported in this article examines
      how the use of gender-inclusive language in news reports affects readers' own
      usage of such forms as well as their mental representation of women and men in
      the respective roles. In the main experiment, German participants (N = 256) read
      short reports about heroes or murderers which contained either masculine generics
      or gender-inclusive forms (feminine-masculine word pairs). Gender-inclusive forms
      enhanced participants' own usage of gender-inclusive language and this resulted
      in more gender-balanced mental representations of these roles. Reading about
      "heroines and heroes" made participants assume a higher percentage of women among
      persons performing heroic acts than reading about "heroes" only, but there was no
      such effect for murderers. A post-test suggested that this might be due to a
      higher accessibility of female exemplars in the category heroes than in the
      category murderers. Importantly, the influence of gender-inclusive language on
      the perceived percentage of women in a role was mediated by speakers' own usage
      of inclusive forms. This suggests that people who encounter gender-inclusive
      forms and are given an opportunity to use them, use them more themselves and in
      turn have more gender-balanced mental representations of social roles. 

PMID- 27047411
TI  - Structure and Relationships of University Instructors' Achievement Goals.
AB  - The present study examines the achievement goals of university instructors,
      particularly the structure of such goals, and their relationship to biographic
      characteristics, other aspects of instructors' motivation, and teaching quality.
      Two hundred and fifty-one university instructors (184 without Ph.D., 97 with
      Ph.D., thereof 51 full professors; 146 males, 92 females) answered a
      questionnaire measuring achievement goals, self-efficacy, and enthusiasm in
      altogether 392 courses. Teaching quality was assessed using reports from 9,241
      students who were attending these courses. Confirmatory factor analyses revealed
      mastery, performance approach, performance avoidance, work avoidance, and
      relational goals as being distinguishable from each other. Distinct relationships
      were found between different instructors' achievement goals, and gender, age, and
      career status as well as self-efficacy and enthusiasm. Hierarchical linear models
      suggested positive associations of instructors' mastery goals with teaching
      quality, while negative associations were indicated for performance avoidance
      goals and work avoidance goals in relation to teaching quality. Exploratory
      analyses conducted due to a quite large correlation between performance approach
      and performance avoidance goals indicated that for university instructors,
      differentiating performance goals into appearance and normative components might
      also be adequate. All in all, the study highlights the auspiciousness of the
      theoretical concept of university instructors' achievement goals and contributes
      to making it comprehensively accessible. 

PMID- 27047412
TI  - Neural Correlates of Direct and Indirect Suppression of Autobiographical
      Memories.
AB  - Research indicates that there are two possible mechanisms by which particular
      target memories can be intentionally forgotten. Direct suppression, which
      involves the suppression of the unwanted memory directly, and is dependent on a
      fronto-hippocampal modulatory process, and, memory substitution, which includes
      directing one's attention to an alternative memory in order to prevent the
      unwanted memory from coming to mind, and involves engaging the caudal prefrontal
      cortex (cPFC) and the mid-ventrolateral prefrontal cortex (VLPFC) regions.
      Research to date, however, has investigated the neural basis of memory
      suppression of relatively simple information. The aim of the current study was to
      use fMRI to identify the neural mechanisms associated with the suppression of
      autobiographical memories. In the present study, 22 participants generated
      memories in response to a series of cue words. In a second session, participants
      learnt these cue-memory pairings, and were subsequently presented with a cue word
      and asked either to recall (think) or to suppress (no-think) the associated
      memory, or to think of an alternative memory in order to suppress the original
      memory (memory-substitution). Our findings demonstrated successful forgetting
      effects in the no-think and memory substitution conditions. Although we found no
      activation in the dorsolateral prefrontal cortex, there was reduced hippocampal
      activation during direct suppression. In the memory substitution condition,
      however, we failed to find increased activation in the cPFC and VLPFC regions.
      Our findings suggest that the suppression of autobiographical memories may rely
      on different neural mechanisms to those established for other types of material
      in memory. 

PMID- 27047413
TI  - Context in Generalized Conversational Implicatures: The Case of Some.
AB  - There is now general agreement about the optionality of scalar implicatures: the
      pragmatic interpretation will be accessed depending on the context relative to
      which the utterance is interpreted. The question, then, is what makes a context
      upper- (vs. lower-) bounding. Neo-Gricean accounts should predict that contexts
      including factual information will enhance the rate of pragmatic interpretations.
      Post-Gricean accounts should predict that contexts including psychological
      attributions will enhance the rate of pragmatic interpretations. We tested two
      factors using the quantifier scale <all, some>: (1) the existence of factual
      information that facilitates the computation of pragmatic interpretations in the
      context (here, the cardinality of the domain of quantification) and (2) the fact
      that the context makes the difference between the semantic and the pragmatic
      interpretations of the target sentence relevant, involving psychological
      attributions to the speaker (here a question using all). We did three
      experiments, all of which suggest that while cardinality information may be
      necessary to the computation of the pragmatic interpretation, it plays a minor
      role in triggering it; highlighting the contrast between the pragmatic and the
      semantic interpretations, while it is not necessary to the computation of the
      pragmatic interpretation, strongly mandates a pragmatic interpretation. These
      results favor Sperber and Wilson's (1995) post-Gricean account over Chierchia's
      (2013) neo-Gricean account. Overall, this suggests that highlighting the
      relevance of the pragmatic vs. semantic interpretations of the target sentence
      makes a context upper-bounding. Additionally, the results give a small advantage
      to the post-Gricean account. 

PMID- 27047414
TI  - The Effectiveness of Somatization in Communicating Distress in Korean and
      American Cultural Contexts.
AB  - Previous research has documented that Asians tend to somatize negative
      experiences to a greater degree than Westerners. It is posited that somatization
      may be a more functional communication strategy in Korean than American context.
      We examined the effects of somatization in communications of distress among
      participants from the US and Korea. We predicted that the communicative benefits
      of somatic words used in distress narratives would depend on the cultural
      contexts. In Study 1, we found that Korean participants used more somatic words
      to communicate distress than US participants. Among Korean participants, but not
      US participants, use of somatic words predicted perceived effectiveness of the
      communication and expectations of positive reactions (e.g., empathy) from others.
      In Study 2, we found that when presented with distress narratives of others,
      Koreans (but not Americans) showed more sympathy in response to narratives using
      somatic words than narratives using emotional words. These findings suggest that
      cultural differences in use of somatization may reflect differential
      effectiveness of somatization in communicating distress across cultural contexts.

PMID- 27047415
TI  - When Love Meets Money: Priming the Possession of Money Influences Mating
      Strategies.
AB  - Money is an important factor that influences the development of romantic
      relationships. The current paper examines how the feeling of having relatively
      more or less money influences human mating strategies in long-term and short-term
      mating contexts under the framework of evolutionary psychology. We recruited
      mainland Chinese college students involved in steady, heterosexual romantic
      relationships to participate in two experiments. In each study, we experimentally
      triggered participants' feelings of having relatively more or less money and then
      examined their thoughts and behaviors related to mating. Results of Study 1
      showed that men who were primed to feel that they had relatively more money were
      less satisfied with their partners' physical attractiveness than those primed to
      feel that they had less money, suggesting that the subjective feeling of having
      more or less money may affect men's preferences regarding the physical appearance
      of a mate in a long-term relationship. Interestingly, this difference was not
      significant for women. Results of Study 2 indicated that both men and women who
      were primed to feel that they had relatively more money exhibited a greater
      "behavioral approach tendency" toward an attractive member of the opposite sex
      than those primed to feel that they had less money. This finding suggests that
      people who feel they have relatively more money may have more interest in an
      attractive alternative than those who feel they have relatively less money. The
      differences in mating strategies between and within the genders brought about by
      money support the evolutionary hypothesis that individuals adopt conditional
      mating strategies in response to environmental conditions. Additionally, the
      results of experimental studies provide evidence for the causal effects of money
      on mating strategies. These findings have both conceptual and practical
      implications for the psychology of evolution and romantic relationships. 

PMID- 27047416
TI  - Graphemic Analysis and the Spoken Language Bias.

PMID- 27047417
TI  - Turn It Off: An Action Research Study of Top Management Influence on Energy
      Conservation in the Workplace.
AB  - This paper reports the results of an intervention study that aimed to encourage
      workplace energy conservation behavior by office-based employees. Taking a co
      production approach we worked with the participating organization to design and
      implement an intervention that used the influence of top management commitment
      and prompts to encourage workplace energy reduction. Whilst past research has
      shown top management is related to workplace pro-environmental behavior, this
      study extends this work by examining a field-based intervention over a
      longitudinal period. The efficacy of the intervention was measured using
      observational and self-reported data over a period of 6 months. Results showed
      that there were significant changes in objective and self-reported energy
      conservation behavior, perceived top management commitment, organizational
      culture, norms, and knowledge regarding energy conservation behavior over the
      course of the study. The findings also demonstrated that the intervention was
      most successful for those behaviors where employees have individual
      responsibility. Implications for future research and practice are discussed. 

PMID- 27047418
TI  - Interest and Inflation Risk: Investor Behavior.
AB  - We examine investor behavior under interest and inflation risk in different
      scenarios. To that end, we analyze the relation between stock returns and
      unexpected changes in nominal and real interest rates and inflation for the US
      stock market. This relation is examined in detail by breaking the results down
      from the US stock market level to sector, sub-sector, and to individual
      industries as the ability of different industries to absorb unexpected changes in
      interest rates and inflation can vary by industry and by contraction and
      expansion sub-periods. While most significant relations are conventionally
      negative, some are consistently positive. This suggests some relevant
      implications on investor behavior. Thus, investments in industries with this
      positive relation can form a safe haven from unexpected changes in real and
      nominal interest rates. Gold has an insignificant beta during recessionary
      conditions hinting that Gold can be a safe haven during recessions. However, Gold
      also has a consistent negative relation to unexpected changes in inflation
      thereby damaging the claim that Gold is a hedge against inflation. 

PMID- 27047419
TI  - Pediatric Blood Cancer Survivors and Tobacco Use across Adolescence and Emerging
      Adulthood: A Narrative Review.
AB  - Scholars underline the pivotal role of tobacco cigarette smoking in
      carcinogenesis process for blood tumors. A controversial debate is represented by
      the diffusion of tobacco use in young cancer survivors that had a previous
      diagnosis of blood tumor during the childhood. Compared with their peers,
      scientific evidence highlights that pediatric survivors have more difficult to
      give-up cigarette smoking. Furthermore, tobacco-smoking is frequently linked with
      others risk behaviors as drinking or substance abuse. In reviewing the main
      knowledge on this topic, authors affirm the need for increasing research on blood
      cancer survivors in order to depict psychological characteristics of pediatric
      blood cancer survivors. Improving health decision-making skills in young
      survivors could reduce the risk to adopt un-healthy behaviors and increase
      psychological wellbeing. Furthermore, authors propose tailored antismoking
      interventions based on the knowledge of the psychological and cognitive factors
      that support smoking during the transition toward emerging-adulthood. 

PMID- 27047420
TI  - Embodied Action Improves Cognition in Children: Evidence from a Study Based on
      Piagetian Conservation Tasks.
AB  - Converging evidence highlights the relevance of embodied cognition in learning
      processes. In this study we evaluate whether embodied action (enaction) improves
      cognitive understanding in children. Using the Piagetian conservation tasks in 6
      7 year olds, we analyzed quantity conservation conceptualization in children who
      were active participants in the transformation process and compared these results
      to those of children who were mere observers of an adult's demonstration (as
      traditionally conducted). The investigation was performed with 105 first-graders.
      Conservation tasks were demonstrated to half the children, while the other half
      actively carried out the transformation of matter. Our findings showed that
      active manipulation of the material helped children recognize quantity invariance
      in a higher proportion than when the demonstration was only observed. That is,
      their enactive experience enabled them to comprehend conservation phenomena more
      easily than if they were merely passive observers. The outcome of this research
      thus emphasizes how active participation benefits cognitive processes in learning
      contexts, promoting autonomy, and agency during childhood. 

PMID- 27047421
TI  - Maternal Talk in Cognitive Development: Relations between Psychological Lexicon,
      Semantic Development, Empathy, and Temperament.
AB  - In this study, we investigated the relationship between mothers' psychological
      lexicon and children's cognitive and socio-emotive development as assessed
      through conceptual and semantic understanding tasks, in addition to the
      traditional tasks of theory of mind. Currently, there is considerable evidence to
      suggest that the frequency of mothers' mental state words used in mother-child
      picture-book reading is linked with children's theory of mind skills.
      Furthermore, mothers' use of cognitive terms is more strongly related to
      children's theory of mind performances than the mothers' references to other
      mental states, such as desires or emotions (Rollo and Buttiglieri, 2009). Current
      literature has established that early maternal input is related to later child
      mental state understanding; however it has not yet clarified which maternal terms
      are most useful for the socio-emotional and cognitive development of the child,
      and which aspect of the cognitive development benefits from the mother-child
      interaction. The present study addresses this issue and focuses on the
      relationship between mothers' mental state talk and children's behavior in
      conceptual and semantic tasks, and in a theory of mind task. In this study fifty
      pairs consisting of mothers and their 3 to 6-year-old children participated in
      two sessions: (1) The mothers read a picture book to their children. To assess
      the maternal psychological lexicon, their narrative was codified according to the
      categories of mental state references used in literature: perceptual, emotional,
      volitional, cognitive, moral, and communicative. (2) After a few days, the
      conceptual and semantic skills of the children (tasks of contextualization and
      classification, memory, and definition of words) and their psychological lexicon
      were assessed. The results suggest close links between the frequency and variety
      of mothers' mental state words and some semantic and conceptual skills of
      children. 

PMID- 27047422
TI  - Search for Expectancy-Inconsistent Information Reduces Uncertainty Better: The
      Role of Cognitive Capacity.
AB  - Motivation and cognitive capacity are key factors in people's everyday struggle
      with uncertainty. However, the exact nature of their interplay in various
      contexts still needs to be revealed. The presented paper reports on two
      experimental studies which aimed to examine the joint consequences of
      motivational and cognitive factors for preferences regarding incomplete
      information expansion. In Study 1 we demonstrate the interactional effect of
      motivation and cognitive capacity on information preference. High need for
      closure resulted in a stronger relative preference for expectancy-inconsistent
      information among non-depleted individuals, but the opposite among cognitively
      depleted ones. This effect was explained by the different informative value of
      questions in comparison to affirmative sentences and the potential possibility of
      assimilation of new information if it contradicts prior knowledge. In Study 2 we
      further investigated the obtained effect, showing that not only questions but
      also other kinds of incomplete information are subject to the same dependency.
      Our results support the expectation that, in face of incomplete information,
      motivation toward closure may be fulfilled efficiently by focusing on expectancy
      inconsistent pieces of data. We discuss the obtained effect in the context of
      previous assumptions that high need for closure results in a simple processing
      style, advocating a more complex approach based on the character of the provided
      information. 

PMID- 27047423
TI  - Guessing versus Choosing an Upcoming Task.
AB  - We compared the effects of guessing vs. choosing an upcoming task. In a task
      switching paradigm with four tasks, two groups of participants were asked to
      either guess or choose which task will be presented next under otherwise
      identical conditions. The upcoming task corresponded to participants' guesses or
      choices in 75 % of the trials. However, only participants in the Choosing
      condition were correctly informed about this, whereas participants in the
      Guessing condition were told that tasks were determined at random. In the
      Guessing condition, we replicated previous findings of a pronounced reduction of
      switch costs in case of incorrect guesses. This switch cost reduction was
      considerably less pronounced with denied choices in the Choosing condition. We
      suggest that in the Choosing condition, the signaling of prediction errors
      associated with denied choices is attenuated because a certain proportion of
      denied choices is consistent with the overall representation of the situation as
      conveyed by task instructions. In the Guessing condition, in contrast, the
      mismatch of guessed and actual task is resolved solely on the level of individual
      trials by strengthening the representation of the actual task. 

PMID- 27047424
TI  - Electroencephalography (EEG) Measures of Neural Connectivity in the Assessment of
      Brain Responses to Salient Auditory Stimuli in Patients with Disorders of
      Consciousness.

PMID- 27047425
TI  - Survey of Expert Opinion on Intelligence: Causes of International Differences in
      Cognitive Ability Tests.
AB  - Following Snyderman and Rothman (1987, 1988), we surveyed expert opinions on the
      current state of intelligence research. This report examines expert opinions on
      causes of international differences in student assessment and psychometric IQ
      test results. Experts were surveyed about the importance of culture, genes,
      education (quantity and quality), wealth, health, geography, climate, politics,
      modernization, sampling error, test knowledge, discrimination, test bias, and
      migration. The importance of these factors was evaluated for diverse countries,
      regions, and groups including Finland, East Asia, sub-Saharan Africa, Southern
      Europe, the Arabian-Muslim world, Latin America, Israel, Jews in the West, Roma
      (gypsies), and Muslim immigrants. Education was rated by N = 71 experts as the
      most important cause of international ability differences. Genes were rated as
      the second most relevant factor but also had the highest variability in ratings.
      Culture, health, wealth, modernization, and politics were the next most important
      factors, whereas other factors such as geography, climate, test bias, and
      sampling error were less important. The paper concludes with a discussion of
      limitations of the survey (e.g., response rates and validity of expert opinions).

PMID- 27047426
TI  - Editorial: How Humans Recognize Objects: Segmentation, Categorization and
      Individual Identification.

PMID- 27047427
TI  - What's on the Inside Counts: A Grounded Account of Concept Acquisition and
      Development.
AB  - Understanding the factors which affect the age of acquisition (AoA) of words and
      concepts is fundamental to understanding cognitive development more broadly.
      Traditionally, studies of AoA have taken two approaches, either exploring the
      effect of linguistic variables such as input frequency (e.g., Naigles and Hoff
      Ginsberg, 1998) or the semantics of the underlying concept, such as concreteness
      or imageability (e.g., Bird et al., 2001). Embodied theories of cognition,
      meanwhile, assume that concepts, even relatively abstract ones, can be grounded
      in the embodied experience. While the focus of such discussions has been mainly
      on grounding in external modalities, more recently some have argued for the
      importance of interoceptive features, or grounding in complex modalities such as
      social interaction. In this paper, we argue for the integration and extension of
      these two strands of research. We demonstrate that the psycholinguistic factors
      traditionally considered to determine AoA are far from sufficient to account for
      the variability observed in AoA data. Given this gap, we propose groundability as
      a new conceptual tool that can measure the degree to which concepts are grounded
      both in external and, critically, internal modalities. We then present a
      mechanistic theory of conceptual representation that can account for
      groundability in addition to the existing variables argued to influence concept
      acquisition in both the developmental and embodied cognition literatures, and
      discuss its implications for future work in concept and cognitive development. 

PMID- 27047428
TI  - Acquiring and Producing Sentences: Whether Learners Use Verb-Specific or Verb
      General Information Depends on Cue Validity.
AB  - Learning to produce sentences involves learning patterns that enable the
      generation of new utterances. Language contains both verb-specific and verb
      general regularities that are relevant to this capacity. Previous research has
      focused on whether one source is more important than the other. We tested whether
      the production system can flexibly learn to use either source, depending on the
      predictive validity of different cues in the input. Participants learned new
      sentence structures in a miniature language paradigm. In three experiments, we
      manipulated whether individual verbs or verb-general mappings better predicted
      the structures heard during learning. Evaluation of participants' subsequent
      production revealed that they could use either the structural preferences of
      individual verbs or abstract meaning-to-form mappings to construct new sentences.
      Further, this choice varied according to cue validity. These results demonstrate
      flexibility within the production architecture and the importance of considering
      how language was learned when discussing how language is used. 

PMID- 27047429
TI  - The General Movement Assessment Helps Us to Identify Preterm Infants at Risk for
      Cognitive Dysfunction.
AB  - Apart from motor and behavioral dysfunctions, deficits in cognitive skills are
      among the well-documented sequelae of preterm birth. However, early
      identification of infants at risk for poor cognition is still a challenge, as no
      clear association between pathological findings based on neuroimaging scans and
      cognitive functions have been detected as yet. The Prechtl General Movement
      Assessment (GMA) has shown its merits for the evaluation of the integrity of the
      young nervous system. It is a reliable tool for identifying infants at risk for
      neuromotor deficits. Recent studies on preterm infants demonstrate that abnormal
      general movements (GMs) also reflect impairments of brain areas involved in
      cognitive development. The aim of this systematic review was to discuss studies
      that included (i) the Prechtl GMA applied in preterm infants, and (ii) cognitive
      outcome measures in six data bases. Seven studies met the inclusion criteria and
      yielded the following results: (a) children born preterm with consistently
      abnormal GMs up to 8 weeks after term had lower intelligence quotients at school
      age than children with an early normalization of GMs; (b) from 3 to 5 months
      after term, several qualitative, and quantitative aspects of the concurrent motor
      repertoire, including postural patterns, were predictive of intelligence at 7-10
      years of age. These findings in 428 individuals born preterm suggest that normal
      GMs along with a normal motor repertoire during the first months after term are
      markers for normal cognitive development until at least age 10. 

PMID- 27047430
TI  - Decent Work: A Psychological Perspective.
AB  - This contribution, which serves as the lead article for the Research Topic
      entitled "From Meaning of Working to Meaningful Lives: The Challenges of
      Expanding Decent Work," explores current challenges in the development and
      operationalization of decent work. Based on an initiative from the International
      Labor Organization [ILO] (1999) decent work represents an aspirational statement
      about the quality of work that should be available to all people who seek to work
      around the globe. Within recent years, several critiques have been raised about
      decent work from various disciplines, highlighting concerns about a retreat from
      the social justice ethos that had initially defined the concept. In addition,
      other scholars have observed that decent work has not included a focus on the
      role of meaning and purpose at work. To address these concerns, we propose that a
      psychological perspective can help to revitalize the decent work agenda by
      infusing a more specific focus on individual experiences and by reconnecting
      decent work to its social justice origins. As an illustration of the advantages
      of a psychological perspective, we explore the rise of precarious work and also
      connect the decent work agenda to the Psychology-of-Working Framework and Theory
      (Blustein, 2006; Duffy et al., 2016). 

PMID- 27047431
TI  - Infant Hand Preference and the Development of Cognitive Abilities.
AB  - Hand preference develops in the first two postnatal years with nearly half of
      infants exhibiting a consistent early preference for acquiring objects. Others
      exhibit a more variable developmental trajectory but by the end of their second
      postnatal year, most exhibit a consistent hand preference for role-differentiated
      bimanual manipulation. According to some forms of embodiment theory, these
      differences in hand use patterns should influence the way children interact with
      their environments, which, in turn, should affect the structure and function of
      brain development. Such early differences in brain development should result in
      different trajectories of psychological development. We present evidence that
      children with consistent early hand preferences exhibit advanced patterns of
      cognitive development as compared to children who develop a hand preference
      later. Differences in the developmental trajectory of hand preference are
      predictive of developmental differences in language, object management skills,
      and tool-use skills. As predicted by Casasanto's body-specificity hypothesis,
      infants with different hand preferences proceed along different developmental
      pathways of cognitive functioning. 

PMID- 27047432
TI  - What Are Shared Emotions (for)?

PMID- 27047433
TI  - A Preliminary Study on the Biased Attention and Interpretation in the Recognition
      of Face-Body Compound of the Individuals with Social Anxiety.
AB  - The present study aimed to investigate the processes through which individuals
      with social anxiety (SA) attend to and interpret compound emotional expressions
      of the face and body. Incongruent face-body compound images that combined an
      angry face (or body) with a fearful, sad, or happy body (or face) were presented
      to a SA group (n = 22) and a healthy control (HC) group (n = 22). The
      participants were instructed to interpret the emotional state of the image, and
      their eye-movements and behavioral responses were measured. The results revealed
      that both group showed longer scanpath length during the recognition of compound
      images which combined angry face with angry, fearful, sadness, or happy body. The
      SA group also showed longer scanpath length in congruent face-body compound
      images of fear and sad. Additionally, the SA group fixated for a shorter period
      of time on the face and longer on the body than the HC group. Regarding emotion
      interpretation, the SA group was more likely to interpret the emotional state of
      incongruent face-body compound images based on the body than the HC group. These
      findings provide a preliminary observation that individuals with SA showed
      different attentional bias pattern by congruency of face-body compound images and
      that it might have biased their interpretations of the emotional states. 

PMID- 27047434
TI  - A Roving Dual-Presentation Simultaneity-Judgment Task to Estimate the Point of
      Subjective Simultaneity.
AB  - The most popular tasks with which to investigate the perception of subjective
      synchrony are the temporal order judgment (TOJ) and the simultaneity judgment
      (SJ). Here, we discuss a complementary approach-a dual-presentation (2x) SJ task
      and focus on appropriate analysis methods for a theoretically desirable "roving"
      design. Two stimulus pairs are presented on each trial and the observer must
      select the most synchronous. To demonstrate this approach, in Experiment 1 we
      tested the 2xSJ task alongside TOJ, SJ, and simple reaction-time (RT) tasks using
      audiovisual stimuli. We interpret responses from each task using detection
      theoretic models, which assume variable arrival times for sensory signals at
      critical brain structures for timing perception. All tasks provide similar
      estimates of the point of subjective simultaneity (PSS) on average, and PSS
      estimates from some tasks were correlated on an individual basis. The 2xSJ task
      produced lower and more stable estimates of model-based (and thus comparable)
      sensory/decision noise than the TOJ. In Experiment 2 we obtained similar results
      using RT, TOJ, ternary, and 2xSJ tasks for all combinations of auditory, visual,
      and tactile stimuli. In Experiment 3 we investigated attentional prior entry,
      using both TOJs and 2xSJs. We found that estimates of prior-entry magnitude
      correlated across these tasks. Overall, our study establishes the practicality of
      the roving dual-presentation SJ task, but also illustrates the additional
      complexity of the procedure. We consider ways in which this task might complement
      more traditional procedures, particularly when it is important to estimate both
      PSS and sensory/decisional noise. 

PMID- 27047435
TI  - Mechanisms of Choice Behavior Shift Using Cue-approach Training.
AB  - Cue-approach training has been shown to effectively shift choices for snack food
      items by associating a cued button-press motor response to particular food items.
      Furthermore, attention was biased toward previously cued items, even when the
      cued item is not chosen for real consumption during a choice phase. However, the
      exact mechanism by which preferences shift during cue-approach training is not
      entirely clear. In three experiments, we shed light on the possible underlying
      mechanisms at play during this novel paradigm: (1) Uncued, wholly predictable
      motor responses paired with particular food items were not sufficient to elicit a
      preference shift; (2) Cueing motor responses early - concurrently with food item
      onset - and thus eliminating the need for heightened top-down attention to the
      food stimulus in preparation for a motor response also eliminated the shift in
      food preferences. This finding reinforces our hypothesis that heightened
      attention at behaviorally relevant points in time is key to changing choice
      behavior in the cue-approach task; (3) Crucially, indicating choice using eye
      movements rather than manual button presses preserves the effect, thus
      demonstrating that the shift in preferences is not governed by a learned motor
      response but more likely via modulation of subjective value in higher associative
      regions, consistent with previous neuroimaging results. Cue-approach training
      drives attention at behaviorally relevant points in time to modulate the
      subjective value of individual items, providing a mechanism for behavior change
      that does not rely on external reinforcement and that holds great promise for
      developing real world behavioral interventions. 

PMID- 27047436
TI  - The Work of Cultural Transition: An Emerging Model.
AB  - In today's uncertain, fluid job market, transnational mobility has intensified.
      Though the concept of cultural transition is increasingly used in sport and
      career research, insight into the processes of how individuals produce their own
      development through work and relationships in shifting cultural patterns of
      meaning remains limited. The transnational industry of sports, in which athletes'
      psychological adjustment to cultural transitions has implications for both
      performance and meaningful life, serves as a backdrop for this article. This
      study applied the life story method to interviews with 15 professional and semi
      professional athletes, focusing particularly on the cultural transition aspect of
      their transnational athletic careers. The aims of the study were to identify the
      developmental tasks of cultural transitions and strategies/mechanisms through
      which cultural transitions were enacted. Three underlying mechanisms of the
      transition process that assisted athletic career adaptability were social
      repositioning, negotiation of cultural practices, and meaning reconstruction.
      Based on the data analyses, a temporal model of cultural transition is proposed.
      The results of this research provide professionals working in the fields of
      career counseling and migrant support with a content framework for enhancing
      migrant workers' adaptabilities and psychological wellbeing. 

PMID- 27047438
TI  - Biofunctional Understanding and Judgment of Size.
AB  - Research has shown that the meaningfulness of the material increases judged size,
      whereas symmetry decreases size judgments. These findings have been interpreted
      in terms of information processing, with a greater quantity of information
      leading to a judgment of larger size. An alternative view based on biofunctional
      understanding theory emphasizes the quality of affordance-triggered biological
      activity as reported and observed in attitudes toward playing sports, effortless
      understanding, knowledge-in-action, meditative wisdom, and body-mind cycle of
      adaptation. This alternative implies that affordance biofunctional activity is
      naturally size-diminishinging as it moves toward coherence and size-expanding as
      it moves away from coherence influencing judgments of size accordingly. Here we
      tested this hypothesis in the realm of sensorimotor integration. Our first
      experiment showed that phonologically unpronounced or symmetric symbols elicit
      smaller size judgments than phonologically pronounced and asymmetric symbols.
      Next, we manipulated the quantity of meaning with the affordance (possibilities
      for biofunctional activity) orthogonally in a second experiment; results
      indicated that meaning affects size judgments only in the absence of phonological
      information. We conclude that the biofunctional activity affordance may be
      responsible for observed differences in size judgment. 

PMID- 27047437
TI  - Recontextualizing Dance Skills: Overcoming Impediments to Motor Learning and
      Expressivity in Ballet Dancers.
AB  - The process of transmitting ballet's complex technique to young dancers can
      interfere with the innate processes that give rise to efficient, expressive and
      harmonious movement. With the intention of identifying possible solutions, this
      article draws on research across the fields of neurology, psychology, motor
      learning, and education, and considers their relevance to ballet as an art form,
      a technique, and a training methodology. The integration of dancers' technique
      and expressivity is a core theme throughout the paper. A brief outline of the
      historical development of ballet's aesthetics and training methods leads into
      factors that influence dancers' performance. An exploration of the role of the
      neuromotor system in motor learning and the acquisition of expert skills reveals
      the roles of sensory awareness, imagery, and intention in cuing efficient,
      expressive movement. It also indicates potentially detrimental effects of
      conscious muscle control, explicit learning and persistent naive beliefs.
      Finally, the paper presents a new theory regarding the acquisition of ballet
      skills. Recontextualization theory proposes that placing a problematic task
      within a new context may engender a new conceptual approach and/or sensory
      intention, and hence the genesis of new motor programs; and that these new
      programs may lead to performance that is more efficient, more rewarding for the
      dancer, more pleasing aesthetically, and more expressive. From an anecdotal point
      of view, this theory appears to be supported by the progress of many dancers at
      various stages of their dancing lives. 

PMID- 27047439
TI  - Making Sense of Corporate Social Responsibility and Work.
AB  - Employees can be a driving force behind organizational corporate social
      responsibility (CSR) efforts, yet the vast majority of literature has focused on
      firm-level understanding and implementation of CSR. Recent literature that
      explores the relationship between employees and CSR has not investigated how
      employees conceive of their role in CSR. We propose that in order to understand
      the factors that affect employee engagement in CSR, we must first understand how
      employees conceptualize the phenomenon of CSR and how that conceptualisation fits
      into their work. Our exploratory, inductive study interviews two cohorts of
      employees, one in a not for profit and the other in a corporate organization,
      revealing stark contrasts in how the different cohorts conceptualize and engage
      in CSR, particularly with regards to how CSR contributes to meaningfulness at
      work. Implications for organizations are discussed. 

PMID- 27047440
TI  - 3D Cinema and Headache: The First Evidential Relation and Analysis of Involved
      Factors.
AB  - BACKGROUND: A possible link between 3D movies and headache (HA) has never been a
      target of specific and systematic investigations. The aim of this study was to
      investigate the relationship between 3D cinema and HA and to evaluate possible
      risk factors of developing HA during or after watching a 3D movie. METHODS: This
      was a prospective, non-randomized, observational study. Six thousand specifically
      designed questionnaires were distributed to consecutive cinema visitors. Relative
      HA risks for 2D- vs. 3D-movie visitors and the effects of background variables
      were analyzed. RESULTS: The questionnaire was filled and returned by 1293
      persons. The mean age of responders was 33.0 +/- 11.3 years. Individuals who
      viewed 3D movies reported HA during or after the movie 1.61 times more often than
      2D-movie viewers (11.1% in 3D vs. 7.2% in 2D movies, p = 0.017). The risk was
      higher in women: 2.65 times for 2D (p = 0.019) and 1.85 times for 3D movies (p =
      0.06), and decreased with age by 4.6% with each year for 2D (p = 0.0035) and by
      3.2% for 3D movies (p = 0.0098). Among 3D-movie visitors, those with previous HAs
      were 4.17 times more prone to get a cinema-induced HA (p = 0.02). The risk was
      the highest for persons with migraine (OR = 3.37, p = 0.001). CONCLUSION: For the
      first time, it was evidentially shown that 3D movies can provoke HA. Persons at
      risk are mostly younger women and/or migraineurs. Based on our results, for those
      belonging to the aforementioned risk groups, it can be mainly recommended to
      choose passive 3D technology and to view movies from the farthest possible
      distance.

PMID- 27047441
TI  - Role of Anticonvulsants in the Management of Posttraumatic Epilepsy.
AB  - Posttraumatic seizures (PTS) have been recognized as a major complication of
      traumatic brain injury (TBI). The annual incidence of TBI in the United States is
      1.7 million. The role of anticonvulsants in the treatment of posttraumatic
      epilepsy (PTE) remains uncertain. Based on current studies, however,
      anticonvulsants have been shown to reduce early PTS occurring within the first 7
      days, but little to no benefits have been shown in late PTS occurring after 7
      days. In this paper, we provide a mini review of the role of anticonvulsants and
      current advances in the management of PTE. 

PMID- 27047442
TI  - Commentary: Systemic, Local, and Imaging Biomarkers of Brain Injury: More Needed,
      and Better Use of Those Already Established?

PMID- 27047444
TI  - Effects of Soccer Heading on Brain Structure and Function.
AB  - Soccer is the most popular sport in the world, with more than 265 million players
      worldwide, including professional and amateur ones. Soccer is unique in
      comparison to other sports, as it is the only sport in which participants
      purposely use their head to hit the ball. Heading is considered as an offensive
      or defensive move whereby the player's unprotected head is used to deliberately
      impact the ball and direct it during play. A soccer player can be subjected to an
      average of 6-12 incidents of heading the ball per competitive game, where the
      ball reaches high velocities. Moreover, in practice sessions, heading training,
      which involves heading the ball repeatedly at low velocities, is common. Although
      the scientific community, as well as the media, has focused on the effects of
      concussions in contact sports, the role of subconcussive impacts, as it can occur
      during heading, has recently gained attention, considering that it may represent
      an additional mechanism of cumulative brain injury. The purpose of this study is
      to review the existing literature regarding the effects of soccer heading on
      brain structure and function. Only in the last years, some investigations have
      addressed the impact of heading on brain structure, by using neuroimaging
      techniques. Similarly, there have been some recent studies investigating
      biochemical markers of brain injury in soccer players. There is evidence of
      association between heading and abnormal brain structure, but the data are still
      preliminary. Also, some studies have suggested that subconcussive head impacts,
      as heading, could cause cognitive impairment, whereas others have not
      corroborated this finding. Questions persist as to whether or not heading is
      deleterious to cognitive functioning. Further studies, especially with
      longitudinal designs, are needed to clarify the clinical significance of heading
      as a cause of brain injury and to identify risk factors. Such investigations
      might contribute to the establishment of safety guidelines that could help to
      minimize the risk of possible adverse effects of soccer on brain structure and
      function. 

PMID- 27047445
TI  - A Prospective Study of Asymptomatic Intracranial Atherosclerotic Stenosis in
      Neurologically Normal Volunteers in a Japanese Cohort.
AB  - Atherosclerotic stenosis of major intracranial arteries is a leading cause of
      ischemic stroke in Asia. However, the long-term prognosis of asymptomatic
      intracranial atherosclerotic stenosis (ICAS) in healthy volunteers has not been
      fully examined. Here, we conducted a longitudinal study to examine the prognosis
      of healthy volunteers with asymptomatic ICAS and to determine the risk factors
      for ICAS, including asymptomatic brain parenchymal lesions. We studied 2,807
      healthy Japanese volunteers with no history of stroke (mean age, 62.0 years).
      They were followed for a mean interval of 64.5 months. The degree of ICAS and the
      presence of asymptomatic brain lesions were assessed by using magnetic resonance
      imaging. Asymptomatic ICAS was detected in 166 volunteers (5.9%) at the initial
      examination. Moderate and mild stenoses were observed in 1.5 and 4.4% of
      patients, respectively. Significant risk factors for ICAS were older age and a
      history of hypertension and/or dyslipidemia. During follow-up, ischemic stroke
      developed in 32 volunteers. Seven strokes occurred in the ICAS group, whose
      stroke incidence rate was higher than that in the non-ICAS group (0.78 vs. 0.18%
      per year). According to a Cox regression analysis, asymptomatic ICAS was an
      independent risk factor for future ischemic stroke after adjustment for age.
      Furthermore, after asymptomatic brain lesions were taken into account, ICAS was
      still a significant risk factor for stroke onset. In conclusion, even mild to
      moderate asymptomatic ICAS was a significant risk factor for future stroke,
      independent of asymptomatic brain lesions, in a healthy Japanese population. Mild
      to moderate ICAS might be a therapeutic target for stroke prevention. 

PMID- 27047443
TI  - Embolic Strokes of Unknown Source and Cryptogenic Stroke: Implications in
      Clinical Practice.
AB  - Up to a third of strokes are rendered cryptogenic or of undetermined etiology.
      This number is specifically higher in younger patients. At times, inadequate
      diagnostic workups, multiple causes, or an under-recognized etiology contributes
      to this statistic. Embolic stroke of undetermined source, a new clinical entity
      particularly refers to patients with embolic stroke for whom the etiology of
      embolism remains unidentified despite through investigations ruling out
      established cardiac and vascular sources. In this article, we review current
      classification and discuss important clinical considerations in these patients;
      highlighting cardiac arrhythmias and structural abnormalities, patent foramen
      ovale, paradoxical sources, and potentially under-recognized, vascular,
      inflammatory, autoimmune, and hematologic sources in relation to clinical
      practice. 

PMID- 27047446
TI  - Mobilization and Manipulation of the Cervical Spine in Patients with Cervicogenic
      Headache: Any Scientific Evidence?
AB  - Cervical mobilization and manipulation are frequently used to treat patients
      diagnosed with cervicogenic headache (CEH); however, there is conflicting
      evidence on the efficacy of these manual therapy techniques. The purpose of this
      review is to investigate the effects of cervical mobilization and manipulation on
      pain intensity and headache frequency, compared to traditional physical therapy
      interventions in patients diagnosed with CEH. A total of 66 relevant studies were
      originally identified through a review of the literature, and the 25 most
      suitable articles were fully evaluated via a careful review of the text.
      Ultimately, 10 studies met the inclusion criteria: (1) randomized controlled
      trial (RCT) or open RCT; the study contained at least two separate groups of
      subjects that were randomly assigned either to a cervical spine mobilization or
      manipulation or a group that served as a comparison; (2) subjects must have had a
      diagnosis of CEH; (3) the treatment group received either spinal mobilization or
      spinal manipulation, while the control group received another physical therapy
      intervention or placebo control; and (4) the study included headache pain and
      frequency as outcome measurements. Seven of the 10 studies had statistically
      significant findings that subjects who received mobilization or manipulation
      interventions experienced improved outcomes or reported fewer symptoms than
      control subjects. These results suggest that mobilization or manipulation of the
      cervical spine may be beneficial for individuals who suffer from CEH, although
      heterogeneity of the studies makes it difficult to generalize the findings. 

PMID- 27047447
TI  - High-Resolution Microfluidic Single-Cell Transcriptional Profiling Reveals
      Clinically Relevant Subtypes among Human Stem Cell Populations Commonly Utilized
      in Cell-Based Therapies.
AB  - Stem cell therapies can promote neural repair and regeneration, yet controversy
      regarding optimal cell source and mechanism of action has slowed clinical
      translation, potentially due to undefined cellular heterogeneity. Single-cell
      resolution is needed to identify clinically relevant subpopulations with the
      highest therapeutic relevance. We combine single-cell microfluidic analysis with
      advanced computational modeling to study for the first time two common sources
      for cell-based therapies, human NSCs and MSCs. This methodology has the potential
      to logically inform cell source decisions for any clinical application. 

PMID- 27047448
TI  - Semicircular Canal Fibrosis as a Biomarker for Lateral Semicircular Canal
      Function Loss.
AB  - BACKGROUND AND PURPOSE: Radiological abnormalities at the level of the
      semicircular canals are frequently observed without known correlation to a
      pathologic condition or function. They include narrowing or sclerosis on computed
      tomography (CT) and narrowing or signal loss on T2-weighted magnetic resonance
      imaging (MRI). Our hypothesis was that these radiological abnormalities at the
      level of the semicircular canals reflect an aspecific but advanced stage of
      vestibular decay. MATERIALS AND METHODS: Retrospective study in 35 consecutive
      patients with bilateral profound deafness eligible for cochlear implantation.
      Electronystagmography, CT, and MRI were performed as part of evaluation for
      cochlear implant candidacy. RESULTS: In our population, 31.4% had a bilateral
      lateral semicircular canal function loss, while 11.4% had a unilateral lateral
      semicircular canal function loss. CT-scan abnormalities did not correlate to
      lateral semicircular canal function loss at a statistically significant level.
      However, abnormalities observed on MRI correlated significantly with ipsilateral
      lateral semicircular canal function loss. This statistically significant
      difference was present not only if abnormalities were observed in at least one of
      the semicircular canals but also if we studied the posterior, superior, and
      lateral semicircular canals separately. CONCLUSION: Semicircular canal
      abnormalities on T2-weighted MRI (including narrowing and/or signal loss in one
      or more semicircular canals) are correlated to lateral semicircular canal
      function loss.

PMID- 27047449
TI  - Effect of Novel Melanocortin Type 2 Receptor Antagonists on the Corticosterone
      Response to ACTH in the Neonatal Rat Adrenal Gland In Vivo and In Vitro.
AB  - Stress-induced increases in neonatal corticosterone demonstrate a unique shift
      from ACTH independence to ACTH dependence between postnatal day 2 (PD2) and day 8
      (PD8) in newborn rats. This shift could be due to the binding of a bioactive, non
      -immunoreactive plasma ligand to the adrenocortical melanocortin 2 receptor
      (MC2R) (ACTH receptor). A potent MC2R antagonist would be useful to evaluate this
      phenomenon in the neonate. Therefore, we investigated the acute corticosterone
      response to ACTH(1-39) injection in rat pups pretreated with newly developed MC2R
      antagonists (GPS1573 and GPS1574), which have not been tested in vivo. The doses
      used in vivo were based on their in vitro potency, with GP1573 being more potent
      than GPS1574. GPS1573 (PD2 and PD8), GPS1574 (PD2 only), or vehicle were injected
      intraperitoneally (ip) 10 min before baseline sampling. Then, 0.001 mg/kg of
      ACTH(1-39) was injected ip, and subsequent blood samples obtained for the
      measurement of plasma corticosterone. Pretreatment of PD2 pups with GPS1573
      demonstrated augmentation, rather than inhibition, of the corticosterone response
      to ACTH. In PD8 pups, pretreatment with 0.1 mg/kg GPS1573, but not 4 mg/kg,
      augmented the corticosterone response to ACTH. Pretreatment with GPS1574
      attenuated the plasma corticosterone response to ACTH at 30 min in PD2 pups. The
      activity of these two compounds in vivo do not match their potency in vitro, with
      GPS1573 leading to a small augmentation of the corticosterone response to ACTH in
      vivo while GPS1574 resulted in inhibition. 

PMID- 27047450
TI  - Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation
      with Gene Expression Data.
AB  - We introduce a manually constructed and curated regulatory network model that
      describes the current state of knowledge of transcriptional regulation of
      Bacillus subtilis. The model corresponds to an updated and enlarged version of
      the regulatory model of central metabolism originally proposed in 2008. We
      extended the original network to the whole genome by integration of information
      from DBTBS, a compendium of regulatory data that includes promoters,
      transcription factors (TFs), binding sites, motifs, and regulated operons.
      Additionally, we consolidated our network with all the information on regulation
      included in the SporeWeb and Subtiwiki community-curated resources on B.
      subtilis. Finally, we reconciled our network with data from RegPrecise, which
      recently released their own less comprehensive reconstruction of the regulatory
      network for B. subtilis. Our model describes 275 regulators and their target
      genes, representing 30 different mechanisms of regulation such as TFs, RNA
      switches, Riboswitches, and small regulatory RNAs. Overall, regulatory
      information is included in the model for ~2500 of the ~4200 genes in B. subtilis
      168. In an effort to further expand our knowledge of B. subtilis regulation, we
      reconciled our model with expression data. For this process, we reconstructed the
      Atomic Regulons (ARs) for B. subtilis, which are the sets of genes that share the
      same "ON" and "OFF" gene expression profiles across multiple samples of
      experimental data. We show how ARs for B. subtilis are able to capture many sets
      of genes corresponding to regulated operons in our manually curated network.
      Additionally, we demonstrate how ARs can be used to help expand or validate the
      knowledge of the regulatory networks by looking at highly correlated genes in the
      ARs for which regulatory information is lacking. During this process, we were
      also able to infer novel stimuli for hypothetical genes by exploring the genome
      expression metadata relating to experimental conditions, gaining insights into
      novel biology. 

PMID- 27047451
TI  - Biogeochemical and Microbial Variation across 5500 km of Antarctic Surface
      Sediment Implicates Organic Matter as a Driver of Benthic Community Structure.
AB  - Western Antarctica, one of the fastest warming locations on Earth, is a unique
      environment that is underexplored with regards to biodiversity. Although pelagic
      microbial communities in the Southern Ocean and coastal Antarctic waters have
      been well-studied, there are fewer investigations of benthic communities and most
      have a focused geographic range. We sampled surface sediment from 24 sites across
      a 5500 km region of Western Antarctica (covering the Ross Sea to the Weddell Sea)
      to examine relationships between microbial communities and sediment geochemistry.
      Sequencing of the 16S and 18S rRNA genes showed microbial communities in
      sediments from the Antarctic Peninsula (AP) and Western Antarctica (WA),
      including the Ross, Amundsen, and Bellingshausen Seas, could be distinguished by
      correlations with organic matter concentrations and stable isotope fractionation
      (total organic carbon; TOC, total nitrogen; TN, and delta(13)C). Overall, samples
      from the AP were higher in nutrient content (TOC, TN, and NH4 (+)) and
      communities in these samples had higher relative abundances of operational
      taxonomic units (OTUs) classified as the diatom, Chaetoceros, a marine cercozoan,
      and four OTUs classified as Flammeovirgaceae or Flavobacteria. As these OTUs were
      strongly correlated with TOC, the data suggests the diatoms could be a source of
      organic matter and the Bacteroidetes and cercozoan are grazers that consume the
      organic matter. Additionally, samples from WA have lower nutrients and were
      dominated by Thaumarchaeota, which could be related to their known ability to
      thrive as lithotrophs. This study documents the largest analysis of benthic
      microbial communities to date in the Southern Ocean, representing almost half the
      continental shoreline of Antarctica, and documents trophic interactions and
      coupling of pelagic and benthic communities. Our results indicate potential
      modifications in carbon sequestration processes related to change in community
      composition, identifying a prospective mechanism that links climate change to
      carbon availability. 

PMID- 27047452
TI  - Comparative Analysis of Cellular Immune Responses in Treated Leishmania Patients
      and Hamsters against Recombinant Th1 Stimulatory Proteins of Leishmania donovani.
AB  - Our prior studies demonstrated that cellular response of T helper 1 (Th1) type
      was generated by a soluble antigenic fraction (ranging from 89.9 to 97.1 kDa) of
      Leishmania donovani promastigote, in treated Leishmania patients as well as
      hamsters and showed significant prophylactic potential against experimental
      visceral leishmaniasis (VL). Eighteen Th1 stimulatory proteins were identified
      through proteomic analysis of this subfraction, out of which 15 were developed as
      recombinant proteins. In the present work, we have evaluated these 15 recombinant
      proteins simultaneously for their comparative cellular responses in treated
      Leishmania patients and hamsters. Six proteins viz. elongation factor-2, enolase,
      aldolase, triose phosphate isomerase, protein disulfide isomerase, and p45
      emerged as most immunogenic as they produced a significant lymphoproliferative
      response, nitric oxide generation and Th1 cytokine response in PBMCs and
      lymphocytes of treated Leishmania patients and hamsters respectively. The results
      suggested that these proteins may be exploited for developing a successful poly
      protein and/or poly-epitope vaccine against VL. 

PMID- 27047453
TI  - Species Specificity of Bacteria Associated to the Brown Seaweeds Lobophora
      (Dictyotales, Phaeophyceae) and Their Potential for Induction of Rapid Coral
      Bleaching in Acropora muricata.
AB  - While reef degradation is occurring worldwide, it is not uncommon to see phase
      shifts from coral to macroalgal dominated reefs. Numerous studies have addressed
      the mechanisms by which macroalgae may outcompete corals and a few recent studies
      highlighted the putative role of bacteria at the interface between macroalgae and
      corals. Some studies suggest that macroalgae may act as vectors and/or foster
      proliferation of microorganisms pathogenic for corals. Using a combination of
      high throughput sequencing, bacterial culturing, and in situ bioassays we
      question if the adversity of macroalgal-associated bacteria to corals is mediated
      by specific bacterial taxa. Using Illumina sequencing, we characterized and
      compared the bacterial community from two Lobophora (Dictyotales, Phaeophyceae)
      species. The two species presented distinctive bacterial communities. Both
      species shared approximately half of their OTUs, mainly the most abundant
      bacteria. Species-specific OTUs belong to Planctomycetes, Proteobacteria, and
      Bacteroidetes. In total, 16 culturable bacterial strain were isolated and
      identified from the Lobophora surface, consisting of 10 genera (from nine
      families, four classes, and three phyla), some of which are not known as, but are
      related to pathogens involved in coral diseases, and others are naturally
      associated to corals. When patches of marine agar with 24 h cultures of each of
      these bacteria were placed in direct contact with the branches of the
      scleractinian coral Acropora muricata, they caused severe bleaching after 24 h
      exposure. Results suggest that regardless of taxonomic affinities, increase in
      density of these bacteria can be adverse to corals. Nevertheless, the microbial
      community associated to macroalgal surface may not represent a threat to corals,
      because the specific bacterial screening and control exerted by the alga
      preventing specific bacterial proliferation. 

PMID- 27047454
TI  - Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive
      Aspergillosis.
AB  - Invasive aspergillosis (IA) is a devastating opportunistic infection and its
      treatment constitutes a considerable burden for the health care system.
      Immunocompromised patients are at an increased risk for IA, which is mainly
      caused by the species Aspergillus fumigatus. An early and reliable diagnosis is
      required to initiate the appropriate antifungal therapy. However, diagnostic
      sensitivity and accuracy still needs to be improved, which can be achieved at
      least partly by the definition of new biomarkers. Besides the direct detection of
      the pathogen by the current diagnostic methods, the analysis of the host response
      is a promising strategy toward this aim. Following this approach, we sought to
      identify new biomarkers for IA. For this purpose, we analyzed gene expression
      profiles of hematological patients and compared profiles of patients suffering
      from IA with non-IA patients. Based on microarray data, we applied a
      comprehensive feature selection using a random forest classifier. We identified
      the transcript coding for the S100 calcium-binding protein B (S100B) as a
      potential new biomarker for the diagnosis of IA. Considering the expression of
      this gene, we were able to classify samples from patients with IA with 82.3%
      sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B
      in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and
      we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An
      influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B
      knockdown. In conclusion, this study covers an effective feature selection
      revealing a key regulator of the human immune response during IA. S100B may
      represent an additional diagnostic marker that in combination with the
      established techniques may improve the accuracy of IA diagnosis. 

PMID- 27047455
TI  - Propagation and Characterization of Influenza Virus Stocks That Lack High Levels
      of Defective Viral Genomes and Hemagglutinin Mutations.
AB  - Influenza virus infections are responsible for more than 250,000 deaths annually.
      Influenza virus isolation, propagation, and characterization protocols are
      critical for completing reproducible basic research studies and for generating
      vaccine seed stocks. Detailed protocols for the isolation and identification of
      influenza virus have been recently reported (Eisfeld et al., 2014). However,
      there are few standardized protocols focused on the propagation and
      characterization of viral isolates, and as a result, viruses propagated in
      different conditions in different laboratories often have distinct in vitro and
      in vivo characteristics. Here, we focus on influenza A virus propagation and
      characterization in the laboratory taking into consideration the overall quality
      and composition of the virus stock to achieve consistency in virus yield,
      virulence, and immunostimulatory activity. 

PMID- 27047456
TI  - Infection with and Carriage of Mycoplasma pneumoniae in Children.
AB  - "Atypical" pneumonia was described as a distinct and mild form of community
      acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered
      and recognized as its cause. M. pneumoniae is detected in CAP patients most
      frequently among school-aged children from 5 to 15 years of age, with a decline
      after adolescence and tapering off in adulthood. Detection rates by polymerase
      chain reaction (PCR) or serology in children with CAP admitted to the hospital
      amount 4-39%. Although the infection is generally mild and self-limiting,
      patients of every age can develop severe or extrapulmonary disease. Recent
      studies indicate that high rates of healthy children carry M. pneumoniae in the
      upper respiratory tract and that current diagnostic PCR or serology cannot
      discriminate between M. pneumoniae infection and carriage. Further, symptoms and
      radiologic features are not specific for M. pneumoniae infection. Thus, patients
      may be unnecessarily treated with antimicrobials against M. pneumoniae.
      Macrolides are the first-line antibiotics for this entity in children younger
      than 8 years of age. Overall macrolides are extensively used worldwide, and this
      has led to the emergence of macrolide-resistant M. pneumoniae, which may be
      associated with severe clinical features and more extrapulmonary complications.
      This review focuses on the characteristics of M. pneumoniae infections in
      children, and exemplifies that simple clinical decision rules may help
      identifying children at high risk for CAP due to M. pneumoniae. This may aid
      physicians in prescribing appropriate first-line antibiotics, since current
      diagnostic tests for M. pneumoniae infection are not reliably predictive. 

PMID- 27047457
TI  - Development of Cefotaxime Impregnated Chitosan as Nano-antibiotics: De Novo
      Strategy to Combat Biofilm Forming Multi-drug Resistant Pathogens.
AB  - Frequent incidents of antibiotic-resistant biofilm forming pathogens in community
      associated and hospital-acquired infections have become a global concern owing to
      failure of conventional therapies. Nano-antibiotics (NABs) are de novo tools to
      overcome the multi-drug resistant mechanisms employed by the superbugs.
      Inhibition of biofilm formation is one of those strategies to curb multi drug
      resistance phenomenon. In the current study, the anti-biofilm and antibacterial
      potential of newly synthesized cefotaxime loaded chitosan based NABs have been
      investigated. Both bare and cefotaxime loaded NABs were prepared by ionotropic
      gelation method. They were found carrying positive zeta potential of more than
      +50 mV, indicating highly stable nano-dispersion. Moreover, microscopic studies
      revealed their size as less than 100 nm. NABs were tested against clinical
      isolates of multi drug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa,
      Escherichia coli, and methicillin resistant Staphylococcus aureus and wherein
      they demonstrated broad-spectrum anti-biofilm and anti-pathogenic activity. Thus,
      in vitro synergistic action of cephalosporin drugs and chitosan polymer at nano
      scale in contrast to free antibiotics can be an improved broad-spectrum strategy
      to thwart resistance mechanisms in both Gram-positive and Gram-negative resistant
      pathogens. 

PMID- 27047458
TI  - Piriformospora indica: Potential and Significance in Plant Stress Tolerance.
AB  - Owing to its exceptional ability to efficiently promote plant growth, protection
      and stress tolerance, a mycorrhiza like endophytic Agaricomycetes fungus
      Piriformospora indica has received a great attention over the last few decades.
      P. indica is an axenically cultiviable fungus which exhibits its versatility for
      colonizing/hosting a broad range of plant species through directly manipulating
      plant hormone-signaling pathway during the course of mutualism. P. indica-root
      colonization leads to a better plant performance in all respect, including
      enhanced root proliferation by indole-3-acetic acid production which in turn
      results into better nutrient-acquisition and subsequently to improved crop growth
      and productivity. Additionally, P. indica can induce both local and systemic
      resistance to fungal and viral plant diseases through signal transduction. P.
      indica-mediated stimulation in antioxidant defense system components and
      expressing stress-related genes can confer crop/plant stress tolerance.
      Therefore, P. indica can biotize micropropagated plantlets and also help these
      plants to overcome transplantation shock. Nevertheless, it can also be involved
      in a more complex symbiotic relationship, such as tripartite symbiosis and can
      enhance population dynamic of plant growth promoting rhizobacteria. In brief, P.
      indica can be utilized as a plant promoter, bio-fertilizer, bioprotector,
      bioregulator, and biotization agent. The outcome of the recent literature
      appraised herein will help us to understand the physiological and molecular bases
      of mechanisms underlying P. indica-crop plant mutual relationship. Together, the
      discussion will be functional to comprehend the usefulness of crop plant-P.
      indica association in both achieving new insights into crop
      protection/improvement as well as in sustainable agriculture production. 

PMID- 27047459
TI  - Composition and Interactions among Bacterial, Microeukaryotic, and T4-like Viral
      Assemblages in Lakes from Both Polar Zones.
AB  - In this study we assess global biogeography and correlation patterns among three
      components of microbial life: bacteria, microeukaryotes, and T4-like myoviruses.
      In addition to environmental and biogeographical considerations, we have focused
      our study on samples from high-latitude pristine lakes from both poles, since
      these simple island-like ecosystems represent ideal ecological models to probe
      the relationships among microbial components and with the environment. Bacterial
      assemblages were dominated by members of the same groups found to dominate
      freshwater ecosystems elsewhere, and microeukaryotic assemblages were dominated
      by photosynthetic microalgae. Despite inter-lake variations in community
      composition, the overall percentages of OTUs shared among sites was remarkable,
      indicating that many microeukaryotic, bacterial, and viral OTUs are globally
      distributed. We observed an intriguing negative correlation between bacterial and
      microeukaryotic diversity values. Notably, our analyses show significant global
      correlations between bacterial and microeukaryotic community structures, and
      between the phylogenetic compositions of bacterial and T4-like virus assemblages.
      Overall, environmental filtering emerged as the main factor driving community
      structures. 

PMID- 27047460
TI  - The Association between Invasive Group A Streptococcal Diseases and Viral
      Respiratory Tract Infections.
AB  - Viral infections of the upper respiratory tract are associated with a variety of
      invasive diseases caused by Streptococcus pyogenes, the group A streptococcus,
      including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia.
      While these polymicrobial infections, or superinfections, are complex, progress
      has been made in understanding the molecular basis of disease. Areas of
      investigation have included the characterization of virus-induced changes in
      innate immunity, differences in bacterial adherence and internalization following
      viral infection, and the efficacy of vaccines in mitigating the morbidity and
      mortality of superinfections. Here, we briefly summarize viral-S. pyogenes
      superinfections with an emphasis on those affiliated with influenza viruses. 

PMID- 27047461
TI  - Environmental Controls Over Actinobacteria Communities in Ecological Sensitive
      Yanshan Mountains Zone.
AB  - The Yanshan Mountains are one of the oldest mountain ranges in the world. They
      are located in an ecologically sensitive zone in northern China near the Hu
      Huanyong Line. In this metagenomic study, we investigated the diversity of
      Actinobacteria in soils at 10 sites (YS1-YS10) on the Yanshan Mountains. First,
      we assessed the effect of different soil prtreatment on Actinobacteria recovery.
      With the soil pretreatment method: air drying of the soil sample, followed by
      exposure to 120 degrees C for 1 h, we observed the higher Actinobacteria
      diversity in a relatively small number of clone libraries. No significant
      differences were observed in the Actinobacterial diversity of soils from sites
      YS2, YS3, YS4, YS6, YS8, YS9, or YS10 (P > 0.1). However, there were differences
      (P < 0.05) from the YS7 site and other sites, especially in response to
      environmental change. And we observed highly significant differences (P < 0.001)
      in Actinobacterial diversity of the soil from YS7 and that from YS4 and YS8
      sites. The climatic characteristics of mean active accumulated temperature,
      annual mean precipitation, and annual mean temperature, and biogeochemical data
      of total phosphorus contributed to the diversity of Actinobacterial communities
      in soils at YS1, YS3, YS4, and YS5 sites. Compared to the climatic factors, the
      biogeochemical factors mostly contributed in shaping the Actinobacterial
      community. This work provides evidence that the diversity of Actinobacterial
      communities in soils from the Yashan Mountains show regional biogeographic
      patterns and that community membership change along the north-south distribution
      of the Hu Huanyong Line. 

PMID- 27047462
TI  - Performance of Denitrifying Microbial Fuel Cell with Biocathode over Nitrite.
AB  - Microbial fuel cell (MFC) with nitrite as an electron acceptor in cathode
      provided a new technology for nitrogen removal and electricity production
      simultaneously. The influences of influent nitrite concentration and external
      resistance on the performance of denitrifying MFC were investigated. The optimal
      effectiveness were obtained with the maximum total nitrogen (TN) removal rate of
      54.80 +/- 0.01 g m(-3) d(-1). It would be rather desirable for the TN removal
      than electricity generation at lower external resistance. Denaturing gradient gel
      electrophoresis suggested that Proteobacteria was the predominant phylum,
      accounting for 35.72%. Thiobacillus and Afipia might benefit to nitrite removal.
      The presence of nitrifying Devosia indicated that nitrite was oxidized to nitrate
      via a biochemical mechanism in the cathode. Ignavibacterium and Anaerolineaceae
      was found in the cathode as a heterotrophic bacterium with sodium acetate as
      substrate, which illustrated that sodium acetate in anode was likely permeated
      through proton exchange membrane to the cathode. 

PMID- 27047463
TI  - Broad Spectrum Antimicrobial Activity of Forest-Derived Soil Actinomycete,
      Nocardia sp. PB-52.
AB  - A mesophilic actinomycete strain designated as PB-52 was isolated from soil
      samples of Pobitora Wildlife Sanctuary of Assam, India. Based on phenotypic and
      molecular characteristics, the strain was identified as Nocardia sp. which shares
      99.7% sequence similarity with Nocardia niigatensis IFM 0330 (NR_112195). The
      strain is a Gram-positive filamentous bacterium with rugose spore surface which
      exhibited a wide range of antimicrobial activity against Gram-positive bacteria
      including methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative
      bacteria, and yeasts. Optimization for the growth and antimicrobial activity of
      the strain PB-52 was carried out in batch culture under shaking condition. The
      optimum growth and antimicrobial potential of the strain were recorded in GLM
      medium at 28 degrees C, initial pH 7.4 of the medium and incubation period of 8
      days. Based on polyketide synthases (PKS) and non-ribosomal peptide synthetases
      (NRPS) gene-targeted PCR amplification, the occurrence of both of these
      biosynthetic pathways was detected which might be involved in the production of
      antimicrobial compounds in PB-52. Extract of the fermented broth culture of PB-52
      was prepared with organic solvent extraction method using ethyl acetate. The
      ethyl acetate extract of PB-52 (EA-PB-52) showed lowest minimum inhibitory
      concentration (MIC) against S. aureus MTCC 96 (0.975 MUg/mL) whereas highest was
      recorded against Klebsiella pneumoniae ATCC 13883 (62.5 MUg/mL). Scanning
      electron microscopy (SEM) revealed that treatment of the test microorganisms with
      EA-PB-52 destroyed the targeted cells with prominent loss of cell shape and
      integrity. In order to determine the constituents responsible for its
      antimicrobial activity, EA-PB-52 was subjected to chemical analysis using gas
      chromatography-mass spectrometry (GC-MS). GC-MS analysis showed the presence of
      twelve different chemical constituents in the extract, some of which are reported
      to possess diverse biological activity. These results confirmed that the presence
      of bioactive constituents in EA-PB-52 could be a promising source for the
      development of potent antimicrobial agents effective against wide range of
      microbial pathogens including MRSA. 

PMID- 27047464
TI  - Role of Trypanosoma cruzi Trans-sialidase on the Escape from Host Immune
      Surveillance.
AB  - Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi, affecting
      millions of people throughout Latin America. The parasite dampens host immune
      response causing modifications in diverse lymphoid compartments, including the
      thymus. T. cruzi trans-sialidase (TS) seems to play a fundamental role in such
      immunopathological events. This unusual enzyme catalyses the transference of
      sialic acid molecules from host glycoconjugates to acceptor molecules placed on
      the parasite surface. TS activity mediates several biological effects leading to
      the subversion of host immune system, hence favoring both parasite survival and
      the establishment of chronic infection. This review summarizes current findings
      on the roles of TS in the immune response during T. cruzi infection. 

PMID- 27047466
TI  - Emerging Seafood Preservation Techniques to Extend Freshness and Minimize Vibrio
      Contamination.
AB  - Globally, the popularity of seafood consumption is increasing exponentially. To
      meet the demands of a growing market, the seafood industry has increasingly been
      innovating ways to keep their products fresh and safe while increasing
      production. Marine environments harbor several species of indigenous
      microorganisms, some of which, including Vibrio spp., may be harmful to humans,
      and all of which are part of the natural microbiota of the seafood. After
      harvest, seafood products are often shipped over large geographic distances,
      sometimes for prolonged periods, during which the food must stay fresh and
      pathogen proliferation must be minimized. Upon arrival there is often a strong
      desire, arising from both culinary and nutritional considerations, to consume
      seafood products raw, or minimally cooked. This supply chain along with popular
      preferences have increased challenges for the seafood industry. This has resulted
      in a desire to develop methodologies that reduce pathogenic and spoilage
      organisms in seafood items to comply with regulations and result in minimal
      changes to the taste, texture, and nutritional content of the final product. This
      mini-review discusses and compares several emerging technologies, such as
      treatment with plant derived natural compounds, phage lysis, high-pressure
      processing, and irradiation for their ability to control pathogenic vibrios,
      limit the growth of spoilage organisms, and keep the desired organoleptic
      properties of the seafood product intact. 

PMID- 27047465
TI  - Giant Viruses of Amoebas: An Update.
AB  - During the 12 past years, five new or putative virus families encompassing
      several members, namely Mimiviridae, Marseilleviridae, pandoraviruses,
      faustoviruses, and virophages were described. In addition, Pithovirus sibericum
      and Mollivirus sibericum represent type strains of putative new giant virus
      families. All these viruses were isolated using amoebal coculture methods. These
      giant viruses were linked by phylogenomic analyses to other large DNA viruses.
      They were then proposed to be classified in a new viral order, the Megavirales,
      on the basis of their common origin, as shown by a set of ancestral genes
      encoding key viral functions, a common virion architecture, and shared major
      biological features including replication inside cytoplasmic factories.
      Megavirales is increasingly demonstrated to stand in the tree of life aside
      Bacteria, Archaea, and Eukarya, and the megavirus ancestor is suspected to be as
      ancient as cellular ancestors. In addition, giant amoebal viruses are visible
      under a light microscope and display many phenotypic and genomic features not
      found in other viruses, while they share other characteristics with parasitic
      microbes. Moreover, these organisms appear to be common inhabitants of our
      biosphere, and mimiviruses and marseilleviruses were isolated from human samples
      and associated to diseases. In the present review, we describe the main features
      and recent findings on these giant amoebal viruses and virophages. 

PMID- 27047467
TI  - Use of Homogeneously-Sized Carbon Steel Ball Bearings to Study Microbially
      Influenced Corrosion in Oil Field Samples.
AB  - Microbially-influenced corrosion (MIC) contributes to the general corrosion rate
      (CR), which is typically measured with carbon steel coupons. Here we explore the
      use of carbon steel ball bearings, referred to as beads (55.0 +/- 0.3 mg; O =
      0.238 cm), for determining CRs. CRs for samples from an oil field in Oceania
      incubated with beads were determined by the weight loss method, using acid
      treatment to remove corrosion products. The release of ferrous and ferric iron
      was also measured and CRs based on weight loss and iron determination were in
      good agreement. Average CRs were 0.022 mm/yr for eight produced waters with high
      numbers (10(5)/ml) of acid-producing bacteria (APB), but no sulfate-reducing
      bacteria (SRB). Average CRs were 0.009 mm/yr for five central processing facility
      (CPF) waters, which had no APB or SRB due to weekly biocide treatment and 0.036
      mm/yr for 2 CPF tank bottom sludges, which had high numbers of APB (10(6)/ml) and
      SRB (10(8)/ml). Hence, corrosion monitoring with carbon steel beads indicated
      that biocide treatment of CPF waters decreased the CR, except where biocide did
      not penetrate. The CR for incubations with 20 ml of a produced water decreased
      from 0.061 to 0.007 mm/yr when increasing the number of beads from 1 to 40. CRs
      determined with beads were higher than those with coupons, possibly also due to a
      higher weight of iron per unit volume used in incubations with coupons. Use of 1
      ml syringe columns, containing carbon steel beads, and injected with 10 ml/day of
      SRB-containing medium for 256 days gave a CR of 0.11 mm/yr under flow conditions.
      The standard deviation of the distribution of residual bead weights, a measure
      for the unevenness of the corrosion, increased with increasing CR. The most
      heavily corroded beads showed significant pitting. Hence the use of uniformly
      sized carbon steel beads offers new opportunities for screening and monitoring of
      corrosion including determination of the distribution of corrosion rates, which
      allows estimation of the probability of high rate events that may lead to
      failure. 

PMID- 27047468
TI  - Indigenous Georgian Wine-Associated Yeasts and Grape Cultivars to Edit the Wine
      Quality in a Precision Oenology Perspective.
AB  - In Georgia, one of the most ancient vine-growing environment, the homemade
      production of wine is still very popular in every rural family and spontaneous
      fermentation of must, without addition of chemical preservatives, is the norm.
      The present work investigated the yeast biodiversity in five Georgian areas
      (Guria, Imereti, Kakheti, Kartli, Ratcha-Lechkhumi) sampling grapes and wines
      from 22 different native cultivars, in 26 vineyards and 19 family cellars. One
      hundred and eighty-two isolates were ascribed to 15 different species by PCR-ITS
      and RFLP, and partial sequencing of D1/D2 domain 26S rDNA gene. Metschnikowia
      pulcherrima (F' = 0.56, I' = 0.32), Hanseniaspora guilliermondii (F' = 0.49, I' =
      0.27), and Cryptococcus flavescens (F' = 0.31, I' = 0.11) were the dominant
      yeasts found on grapes, whereas Saccharomyces cerevisiae showed the highest
      prevalence into wine samples. Seventy four isolates with fermentative potential
      were screened for oenological traits such as ethanol production, resistance to
      SO2, and acetic acid, glycerol and H2S production. Three yeast strains
      (Kluyveromyces marxianus UMY207, S. cerevisiae UMY255, Torulaspora delbrueckii
      UMY196) were selected and separately inoculated in vinifications experiments at a
      Georgian cellar. Musts were prepared from healthy grapes of local varieties,
      Goruli Mtsvane (white berry cultivar) and Saperavi (black berry cultivar).
      Physical ( degrees Brix) and microbial analyses (plate counts) were performed to
      monitor the fermentative process. The isolation of indigenous S. cerevisiae
      yeasts beyond the inoculated strains indicated that a co-presence occurred during
      the vinification tests. Results from quantitative GC-FID analysis of volatile
      compounds revealed that the highest amount of fermentation flavors, such as 4
      ethoxy-4-oxobutanoic acid (monoethyl succinate), 2-methylpropan-1-ol, ethyl 2
      hydroxypropanoate, and 2-phenylethanol, were significantly more produced in
      fermentation conducted in Saperavi variety inoculated with K. marxianus, whereas
      other aromatic compounds like 3-methylbutyl acetate, ethyl hexanoate and
      dihydrofuran-2(3H)-one (gamma- butyrolactone) showed a higher content in Goruli
      Mtsvane variety samples fermented by S. cerevisiae. The selected yeast strains
      have proved to be promising for enhancing the flavor potential in low aromatic
      Georgian cultivars. This work intends to be a knowledge contribution for a
      precision oenology toward the strategic concept of "one grape variety-one yeast".

PMID- 27047469
TI  - The Adenylate-Forming Enzymes AfeA and TmpB Are Involved in Aspergillus nidulans
      Self-Communication during Asexual Development.
AB  - Aspergillus nidulans asexual sporulation (conidiation) is triggered by different
      environmental signals and involves the differentiation of specialized structures
      called conidiophores. The elimination of genes flbA-E, fluG, and tmpA results in
      a fluffy phenotype characterized by delayed conidiophore development and
      decreased expression of the conidiation essential gene brlA. While flbA-E encode
      regulatory proteins, fluG and tmpA encode enzymes involved in the biosynthesis of
      independent signals needed for normal conidiation. Here we identify afeA and tmpB
      as new genes encoding members the adenylate-forming enzyme superfamily, whose
      inactivation cause different fluffy phenotypes and decreased conidiation and brlA
      expression. AfeA is most similar to unknown function coumarate ligase-like (4CL
      Lk) enzymes and consistent with this, a K544N active site modification eliminates
      AfeA function. TmpB, identified previously as a larger homolog of the
      oxidoreductase TmpA, contains a NRPS-type adenylation domain. A high degree of
      synteny in the afeA-tmpA and tmpB regions in the Aspergilli suggests that these
      genes are part of conserved gene clusters. afeA, tmpA, and tmpB double and triple
      mutant analysis as well as afeA overexpression experiments indicate that TmpA and
      AfeA act in the same conidiation pathway, with TmpB acting in a different
      pathway. Fluorescent protein tagging shows that functional versions of AfeA are
      localized in lipid bodies and the plasma membrane, while TmpA and TmpB are
      localized at the plasma membrane. We propose that AfeA participates in the
      biosynthesis of an acylated compound, either a p-cuomaryl type or a fatty acid
      compound, which might be oxidized by TmpA and/or TmpB, while TmpB adenylation
      domain would be involved in the activation of a hydrophobic amino acid, which in
      turn would be oxidized by the TmpB oxidoreductase domain. Both, AfeA-TmpA and
      TmpB signals are involved in self-communication and reproduction in A. nidulans. 

PMID- 27047470
TI  - The Bacteriophage Carrier State of Campylobacter jejuni Features Changes in Host
      Non-coding RNAs and the Acquisition of New Host-derived CRISPR Spacer Sequences.
AB  - Incorporation of self-derived CRISPR DNA protospacers in Campylobacter jejuni
      PT14 occurs in the presence of bacteriophages encoding a CRISPR-like Cas4
      protein. This phenomenon was evident in carrier state infections where both
      bacteriophages and host are maintained for seemingly indefinite periods as stable
      populations following serial passage. Carrier state cultures of C. jejuni PT14
      have greater aerotolerance in nutrient limited conditions, and may have arisen as
      an evolutionary response to selective pressures imposed during periods in the
      extra-intestinal environment. A consequence of this is that bacteriophage and
      host remain associated and able to survive transition periods where the chances
      of replicative success are greatly diminished. The majority of the bacteriophage
      population do not commit to lytic infection, and conversely the bacterial
      population tolerates low-level bacteriophage replication. We recently examined
      the effects of Campylobacter bacteriophage/C. jejuni PT14 CRISPR spacer
      acquisition using deep sequencing strategies of DNA and RNA-Seq to analyze
      carrier state cultures. This approach identified de novo spacer acquisition in C.
      jejuni PT14 associated with Class III Campylobacter phages CP8/CP30A but spacer
      acquisition was oriented toward the capture of host DNA. In the absence of
      bacteriophage predation the CRISPR spacers in uninfected C. jejuni PT14 cultures
      remain unchanged. A distinct preference was observed for incorporation of self
      derived protospacers into the third spacer position of the C. jejuni PT14 CRISPR
      array, with the first and second spacers remaining fixed. RNA-Seq also revealed
      the variation in the synthesis of non-coding RNAs with the potential to bind
      bacteriophage genes and/or transcript sequences. 

PMID- 27047471
TI  - Dual Acting Neuraminidase Inhibitors Open New Opportunities to Disrupt the Lethal
      Synergism between Streptococcus pneumoniae and Influenza Virus.
AB  - Secondary infections with Streptococcus pneumoniae cause severe pneumonia and
      enhance lethality during influenza epidemics and pandemics. Structural and
      functional similarities with viral neuraminidase (NA) suggest that the highly
      prevalent pneumococcal NAs, NanA and NanB, might contribute to this lethal
      synergism by supporting viral replication and that dual acting NA inhibitors
      (NAIs) will disrupt it. To verify this hypothesis, NanA and NanB were expressed
      in E. coli. After confirming their activity in enzyme assays, in vitro models
      with influenza virus A/Jena/8178/09 (Jena/8178) and the recombinant NanA or NanB
      (rNanA and rNanB) were established in A549 and MDCK cells to mimic the role of
      these pneumococcal NAs during co-infection. Studies on the influence of both NAs
      on viral receptor expression, spread, and yield revealed a distinct effect of
      NanA and NanB on viral replication in these in vitro models. Both enzymes were
      able to support Jena/8178 replication at certain concentrations. This synergism
      was disrupted by the NAIs oseltamivir, DANA, katsumadain A, and artocarpin
      exerting an inhibitory effect on viral NA and NanA. Interestingly, katsumadain A
      and artocarpin inhibited rNanA and rNanB similarly. Zanamivir did not show
      activity. These results demonstrate a key role of pneumococcal NAs in the lethal
      synergism with influenza viruses and reveal opportunities for its effective
      disruption. 

PMID- 27047472
TI  - Commentary: Blurring Borders: Innate Immunity with Adaptive Features.

PMID- 27047473
TI  - Zinc-Induced Transposition of Insertion Sequence Elements Contributes to
      Increased Adaptability of Cupriavidus metallidurans.
AB  - Bacteria can respond to adverse environments by increasing their genomic
      variability and subsequently facilitating adaptive evolution. To demonstrate
      this, the contribution of Insertion Sequence (IS) elements to the genetic
      adaptation of Cupriavidus metallidurans AE126 to toxic zinc concentrations was
      determined. This derivative of type strain CH34, devoid of its main zinc
      resistance determinant, is still able to increase its zinc resistance level.
      Specifically, upon plating on medium supplemented with a toxic zinc
      concentration, resistant variants arose in which a compromised cnrYX regulatory
      locus caused derepression of CnrH sigma factor activity and concomitant induction
      of the corresponding RND-driven cnrCBA efflux system. Late-occurring zinc
      resistant variants likely arose in response to the selective conditions, as they
      were enriched in cnrYX disruptions caused by specific IS elements whose
      transposase expression was found to be zinc-responsive. Interestingly, deletion
      of cnrH, and consequently the CnrH-dependent adaptation potential, still enabled
      adaptation by transposition of IS elements (ISRme5 and IS1086) that provided
      outward-directed promoters driving cnrCBAT transcription. Finally, adaptation to
      zinc by IS reshuffling can also enhance the adaptation to subsequent
      environmental challenges. Thus, transposition of IS elements can be induced by
      stress conditions and play a multifaceted, pivotal role in the adaptation to
      these and subsequent stress conditions. 

PMID- 27047474
TI  - Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and
      Induces Apoptosis-Like Cell Death in Cryptococcus neoformans.
AB  - OBJECTIVES: Cryptococcus neoformans is an opportunistic fungus that causes fatal
      meningoencephalitis especially in AIDS patients. There is an increasing need for
      discovery of new anti-cryptococcal drugs due to emergence of resistance cases in
      recent years. In this study, we aim to elucidate the antifungal effect of
      triclosan against C. neoformans. METHODS: Minimal inhibitory concentration (MIC)
      of triclosan in different C. neoformans strains was first examined. The in vitro
      interactions between triclosan and two standard anti-fungal drugs (amphotericin B
      and fluconazole) were further evaluated by microdilution checkerboard assay.
      Mechanism of triclosan fungicidal activity was then investigated by viewing the
      cell morphology under transmission electron microscope. RESULTS: We reported that
      triclosan potently inhibited the growth of C. neoformans. A combination of
      triclosan with amphotericin B or with fluconazole enhanced their fungicidal
      effects. Triclosan-treated C. neoformans displayed characteristics such as
      nuclear chromatin condensation, extensive intracellular vacuolation and
      mitochondrial swelling, indicating that triclosan triggered apoptosis-like cell
      death. CONCLUSION: In summary, our report suggests triclosan as an independent
      drug or synergent for C. neoformans treatment.

PMID- 27047475
TI  - Identification and Partial Characterization of a Novel UDP-N
      Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase
      Fusion Enzyme from Verrucomicrobium spinosum DSM 4136(T).
AB  - The enzymes involved in synthesizing the bacterial cell wall are attractive
      targets for the design of antibacterial compounds, since this pathway is
      essential for bacteria and is absent in animals, particularly humans. A survey of
      the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest
      free-living relative to bacteria from the Chlamydiales phylum, shows genetic
      evidence that Verrucomicrobium spinosum possesses a novel fusion open reading
      frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is
      predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase
      (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the
      cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses
      using functional complementation showed that the fusion gene was able to
      complement Escherichia coli murB and murC temperature sensitive mutants. The
      purified recombinant fusion enzyme (MurB/C Vs ) was shown to be endowed with UDP
      N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that
      the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a
      temperature optimum of 44-46 degrees C. Its apparent K m values for ATP, UDP
      MurNAc, and l-alanine were 470, 90, and 25 MUM, respectively. However, all
      attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase
      (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity
      search and phylogenetic analysis revealed that this fusion enzyme could only be
      identified in specific lineages within the Verrucomicrobia phylum. 

PMID- 27047477
TI  - The History of Mycoplasma pneumoniae Pneumonia.
AB  - In the United States in the 1930s, although the pathogen was not known, atypical
      pneumonia was clinically distinguished from pneumococcal pneumonia by its
      resistance to sulfonamides. Reimann (1938) reported seven patients with an
      unusual form of tracheo bronchopneumonia and severe constitutional symptoms. He
      believed the clinical picture of this disease differed from that of the disease
      caused by influenza viruses or known bacteria and instead suspected "primary
      atypical pneumonia." For many years, the responsible infectious agent was
      tentatively classified as a filterable virus that could pass through a Seitz
      filter to remove bacteria and was reported to be a psittacosis-like or new virus.
      After that, Eaton et al. (1942, 1944, 1945) identified an agent that was the
      principal cause of primary atypical pneumonia using cotton rats, hamsters, and
      chick embryos. Eaton et al. (1942, 1944, 1945) did not perform an inoculation
      study in human volunteers. During the 1940s, there were three groups engaged in
      discovering the etiology of the primary atypical pneumonia. (1) Commission on
      Acute Respiratory Diseases Diseases directed by John Dingle, (2) Dr. Monroe
      Eaton's group, the Virus Research Laboratory of the California State Public
      Health Department, (3) The Hospital of the Rockefeller Institute for Medical
      Research directed by Horsfall. During 1940s, the members of the Commission on
      Acute Respiratory Diseases concluded that the bacteria-free filtrates obtained
      from the patients, presumably containing a virus, could induce primary atypical
      pneumonia in human volunteers via Pinehurst trials. During 1950s, serological
      approaches for identification of the Eaton agent developed such as Fluorescent
      Stainable Antibody, and at the beginning of the1960s, the Eaton agent
      successfully grew in media, and finally accepted as a cause of primary atypical
      pneumonia. Thus, technical difficulties with visualizing the agent and failure to
      recognize the full significance of the Pinehurst transmission experiments
      resulted in a lapse of 20 years before acceptance of the Eaton agent as
      Mycoplasma pneumoniae. This review describes the history of M. pneumoniae
      pneumonia with a special focus on the recognition between the 1930 and 1960s of
      the Eaton agent as the infectious cause. 

PMID- 27047476
TI  - Diversity and Metabolic Potentials of Subsurface Crustal Microorganisms from the
      Western Flank of the Mid-Atlantic Ridge.
AB  - Deep-sea oceanic crust constitutes the largest region of the earth's surface.
      Accumulating evidence suggests that unique microbial communities are supported by
      iron cycling processes, particularly in the young (<10 million-year old), cool
      (<25 degrees C) subsurface oceanic crust. To test this hypothesis, we
      investigated the microbial abundance, diversity, and metabolic potentials in the
      sediment-buried crust from "North Pond" on western flank of the Mid-Atlantic
      Ridge. Three lithologic units along basement Hole U1383C were found, which
      typically hosted ~10(4) cells cm(-3) of basaltic rock, with higher cell densities
      occurring between 115 and 145 m below seafloor. Similar bacterial community
      structures, which are dominated by Gammaproteobacterial and Sphingobacterial
      species closely related to iron oxidizers, were detected regardless of variations
      in sampling depth. The metabolic potentials of the crust microbiota were assayed
      by metagenomic analysis of two basalt enrichments which showed similar bacterial
      structure with the original sample. Genes coding for energy metabolism involved
      in hydrocarbon degradation, dissimilatory nitrate reduction to ammonium,
      denitrification and hydrogen oxidation were identified. Compared with other
      marine environments, the metagenomes from the basalt-hosted environments were
      enriched in pathways for Fe(3+) uptake, siderophore synthesis and uptake, and Fe
      transport, suggesting that iron metabolism is an important energy production and
      conservation mechanism in this system. Overall, we provide evidence that the
      North Pond crustal biosphere is dominated by unique bacterial groups with the
      potential for iron-related biogeochemical cycles. 

PMID- 27047478
TI  - Formate-Dependent Microbial Conversion of CO2 and the Dominant Pathways of
      Methanogenesis in Production Water of High-temperature Oil Reservoirs Amended
      with Bicarbonate.
AB  - CO2 sequestration in deep-subsurface formations including oil reservoirs is a
      potential measure to reduce the CO2 concentration in the atmosphere. However, the
      fate of the CO2 and the ecological influences in carbon dioxide capture and
      storage (CDCS) facilities is not understood clearly. In the current study, the
      fate of CO2 (in bicarbonate form; 0~90 mM) with 10 mM of formate as electron
      donor and carbon source was investigated with high-temperature production water
      from oilfield in China. The isotope data showed that bicarbonate could be reduced
      to methane by methanogens and major pathway of methanogenesis could be syntrophic
      formate oxidation coupled with CO2 reduction and formate methanogenesis under the
      anaerobic conditions. The bicarbonate addition induced the shift of microbial
      community. Addition of bicarbonate and formate was associated with a decrease of
      Methanosarcinales, but promotion of Methanobacteriales in all treatments.
      Thermodesulfovibrio was the major group in all the samples and Thermacetogenium
      dominated in the high bicarbonate treatments. The results indicated that CO2 from
      CDCS could be transformed to methane and the possibility of microbial CO2
      conversion for enhanced microbial energy recovery in oil reservoirs. 

PMID- 27047479
TI  - Food Allergy and Helicobacter pylori Infection: A Systematic Review.
AB  - INTRODUCTION: Based on the hygiene hypothesis, a low prevalence of Helicobacter
      pylori (H. pylori) infection may explain the recent high prevalence of allergic
      diseases including food allergy. However, there are very few studies that
      investigate the relationship between H. pylori and food allergy. SUMMARY: We
      searched for PubMed, Ovid Medline and the Cochrane library for relevant articles
      published in English from inception to November 2015. The inverse relationship
      between H. pylori and food allergy remains unproven because of contradictory and
      limited evidence at the moment. Likewise, only limited studies have examined the
      relationship between CagA; one of H. pylori virulence factor and food allergy. On
      the other hand, in vitro evidence seems to point out a role of H. pylori in the
      causation of food allergy. The inconsistent results from epidemiological data may
      be due to small sample size, heterogeneous populations and unstandardised methods
      or food allergens. CONCLUSION: Available studies do not support the role of H.
      pylori in food allergy.

PMID- 27047480
TI  - 3-Econsystems: MicroRNAs, Receptors, and Latent Viruses; Some Insights Biology
      Can Gain from Economic Theory.
AB  - This mini-review describes three biological systems. All three include competing
      molecules and a limiting molecule that binds the competing molecules. Such
      systems are extensively researched by economists. In fact, the issue of limited
      resources is the defining feature of economic systems. Therefore, we call these
      systems "econsystems." In an econsystem, the allocation of the limiting molecule
      between the competing molecules determines the behavior of the system. A cell is
      an example of an econsystem. Therefore, a change in the allocation of a limiting
      molecule as a result of, for instance, an abnormal change in the concentration of
      one of the competing molecules, may result in abnormal cellular behavior, and
      disease. The first econsystem described in this mini-review includes a long non
      coding RNA and a messenger RNA (lncRNA and mRNA). The limiting molecule is a
      microRNA (miRNA). The lncRNA and mRNA are known as competing endogenous RNAs
      (ceRNAs). The second econsystem includes two receptors, and the limiting molecule
      is a ligand. The third econsystem includes a cis-regulatory element of a latent
      virus and that of a human gene. The limiting molecule is a transcription complex
      that binds both cis-elements. 

PMID- 27047482
TI  - Translational Inhibition of CTX-M Extended Spectrum beta-Lactamase in Clinical
      Strains of Escherichia coli by Synthetic Antisense Oligonucleotides Partially
      Restores Sensitivity to Cefotaxime.
AB  - Synthetic antisense oligomers are DNA mimics that can specifically inhibit gene
      expression at the translational level by ribosomal steric hindrance. They bind to
      their mRNA targets by Watson-Crick base pairing and are resistant to degradation
      by both nucleases and proteases. A 25-mer phosphorodiamidate morpholino oligomer
      (PMO) and a 13-mer polyamide (peptide) nucleic acid (PNA) were designed to target
      mRNA (positions -4 to +21, and -17 to -5, respectively) close to the
      translational initiation site of the extended-spectrum beta-lactamase resistance
      genes of CTX-M group 1. These antisense oligonucleotides were found to inhibit
      beta-lactamase activity by up to 96% in a cell-free translation-transcription
      coupled system using an expression vector carrying a bla CTX-M-15 gene cloned
      from a clinical isolate. Despite evidence for up-regulation of CTX-M gene
      expression, they were both found to significantly restore sensitivity to
      cefotaxime (CTX) in E. coli AS19, an atypical cell wall permeable mutant, in a
      dose dependant manner (0-40 nM). The PMO and PNA were covalently bound to the
      cell penetrating peptide (CPP; (KFF)3K) and both significantly (P < 0.05)
      increased sensitivity to CTX in a dose dependent manner (0-40 nM) in field and
      clinical isolates harboring CTX-M group 1 beta-lactamases. Antisense
      oligonucleotides targeted to the translational initiation site and Shine-Dalgarno
      region of bla CTX-M-15 inhibited gene expression, and when conjugated to a cell
      penetrating delivery vehicle, partially restored antibiotic sensitivity to both
      field and clinical isolates. 

PMID- 27047481
TI  - Mucus Sugar Content Shapes the Bacterial Community Structure in Thermally
      Stressed Acropora muricata.
AB  - It has been proposed that the chemical composition of a coral's mucus can
      influence the associated bacterial community. However, information on this topic
      is rare, and non-existent for corals that are under thermal stress. This study
      therefore compared the carbohydrate composition of mucus in the coral Acropora
      muricata when subjected to increasing thermal stress from 26 to 31 degrees C, and
      determined whether this composition correlated with any changes in the bacterial
      community. Results showed that, at lower temperatures, the main components of
      mucus were N-acetyl glucosamine and C6 sugars, but these constituted a
      significantly lower proportion of the mucus in thermally stressed corals. The
      change in the mucus composition coincided with a shift from a gamma
      Proteobacteria- to a Verrucomicrobiae- and alpha-Proteobacteria-dominated
      community in the coral mucus. Bacteria in the class Cyanobacteria also started to
      become prominent in the mucus when the coral was thermally stressed. The increase
      in the relative abundance of the Verrucomicrobiae at higher temperature was
      strongly associated with a change in the proportion of fucose, glucose, and
      mannose in the mucus. Increase in the relative abundance of alpha-Proteobacteria
      were associated with GalNAc and glucose, while the drop in relative abundance of
      gamma-Proteobacteria at high temperature coincided with changes in fucose and
      mannose. Cyanobacteria were highly associated with arabinose and xylose. Changes
      in mucus composition and the bacterial community in the mucus layer occurred at
      29 degrees C, which were prior to visual signs of coral bleaching at 31 degrees
      C. A compositional change in the coral mucus, induced by thermal stress could
      therefore be a key factor leading to a shift in the associated bacterial
      community. This, in turn, has the potential to impact the physiological function
      of the coral holobiont. 

PMID- 27047483
TI  - Shiga Toxin-Producing Escherichia coli in Plateau Pika (Ochotona curzoniae) on
      the Qinghai-Tibetan Plateau, China.
AB  - Shiga toxin-producing Escherichia coli (STEC) are an emerging group of zoonotic
      pathogens. Ruminants are the natural reservoir of STEC. In this study we
      determined the prevalence and characteristics of the STEC in plateau pika
      (Ochotona curzoniae) on the Qinghai-Tibetan Plateau, China. A total of 1116 pika
      samples, including 294 intestinal contents samples, 317 fecal samples, and 505
      intestinal contents samples, were collected from May to August in the years 2012,
      2013, and 2015, respectively. Twenty-one samples (1.88%) yielded at least one
      STEC isolate; in total, 22 STEC isolates were recovered. Thirteen different O
      serogroups and 14 serotypes were identified. One stx 1 subtype (stx 1a) and three
      stx 2 subtypes (stx 2a, stx 2b, and stx 2d) were present in the STEC isolates.
      Fifteen, fourteen, and three STEC isolates harbored the virulence genes ehxA,
      subA, and astA, respectively. Adherence-associated genes iha and saa were,
      respectively, present in 72.73 and 68.18% of the STEC isolates. Twenty
      antibiotics were active against all the STEC isolates; all strains were resistant
      to penicillin G, and some to cephalothin or streptomycin. The 22 STEC isolates
      were divided into 16 pulsed-field gel electrophoresis patterns and 12 sequence
      types. Plateau pikas may play a role in the ongoing circulation of STEC in the
      Qinghai-Tibetan plateau. This study provides the first report on STEC in plateau
      pikas and new information about STEC reservoirs in wildlife. Based on the
      serotypes, virulence gene profiles and multi-locus sequence typing (MLST)
      analysis, the majority of these pika STECs may pose a low public health risk. 

PMID- 27047485
TI  - Mycobacterial Interspersed Repetitive Unit Can Predict Drug Resistance of
      Mycobacterium tuberculosis in China.
AB  - BACKGROUND: Recently, Mycobacterial Interspersed Repetitive Unit (MIRU) was
      supposed to be associated with drug resistance in Mycobacterium tuberculosis (M.
      tuberculosis), but whether the association exists actually in local strains in
      China was still unknown. This research was conducted to explore that association
      and the predictability of MIRU to drug resistance of Tuberculosis (TB). METHODS:
      The clinical isolates were collected and the susceptibility test were conducted
      with Lowenstein-Jensen (LJ) medium for five anti-TB drug. Based on PCR of MIRU
      VNTR (Variable Number of Tandem Repeat) genotyping, we tested the number of the
      repeat unite of MIRU. Then, we used logistic regression to evaluate the
      association between 15 MIRU and drug resistance. In addition, we explored the
      most suitable MIRU locus of identified MIRU loci for drug resistance by
      multivariate logistic regression. RESULTS: Of the 102 strains, one isolate was
      resistant to rifampicin and one isolate was resistant to streptomycin. Among
      these fifteen MIRU, there was a association between MIRU loci polymorphism and
      anti-tuberculosis drug resistance, ETRB (P = 0.03, OR = 0.19, 95% CI 0.05-0.81)
      and ETRC (P = 0.01, OR = 0.14, 95% CI 0.03-0.64) were negatively related to
      isoniazid resistance; MIRU20 (P = 0.05, OR = 2.87, 95% CI 1.01-8.12) was
      positively associated with ethambutol resistance; and QUB11a (P = 0.02, OR =
      0.79, 95% CI 0.65-0.96) was a negative association factor of p-aminosalicylic
      acid resistance. CONCLUSION: Our research showed that MIRU loci may predict drug
      resistance of tuberculosis in China. However, the mechanism still needs further
      exploration.

PMID- 27047486
TI  - Induced Bacterial Cross-Resistance toward Host Antimicrobial Peptides: A Worrying
      Phenomenon.
AB  - Bacterial resistance to conventional antibiotics has reached alarming levels,
      threatening to return to the pre-antibiotic era. Therefore, the search for new
      antimicrobial compounds that overcome the resistance phenomenon has become a
      priority. Antimicrobial peptides (AMPs) appear as one of the most promising
      antibiotic medicines. However, in recent years several AMP-resistance mechanisms
      have been described. Moreover, the AMP-resistance phenomenon has become more
      complex due to its association with cross-resistance toward AMP effectors of the
      host innate immune system. In this context, the use of AMPs as a therapeutic
      option could be potentially hazardous, since bacteria could develop resistance
      toward our innate immune system. Here, we review the findings of major studies
      that deal with the AMP cross-resistance phenomenon. 

PMID- 27047484
TI  - Review: Diversity of Microorganisms in Global Fermented Foods and Beverages.
AB  - Culturalable and non-culturable microorganisms naturally ferment majority of
      global fermented foods and beverages. Traditional food fermentation represents an
      extremely valuable cultural heritage in most regions, and harbors a huge genetic
      potential of valuable but hitherto undiscovered strains. Holistic approaches for
      identification and complete profiling of both culturalable and non-culturable
      microorganisms in global fermented foods are of interest to food microbiologists.
      The application of culture-independent technique has thrown new light on the
      diversity of a number of hitherto unknown and non-cultural microorganisms in
      naturally fermented foods. Functional bacterial groups ("phylotypes") may be
      reflected by their mRNA expression in a particular substrate and not by mere DNA
      level detection. An attempt has been made to review the microbiology of some
      fermented foods and alcoholic beverages of the world. 

PMID- 27047487
TI  - The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against
      Haemophilus parasuis.
AB  - The aim of this study was to establish antimicrobial susceptibility breakpoints
      for tilmicosin against Haemophilus parasuis, which is an important pathogen of
      respiratory tract infections. The minimum inhibitory concentrations (MICs) of 103
      H. parasuis isolates were determined by the agar dilution method. The wild type
      (WT) distribution and epidemiologic cutoff value (ECV) were evaluated by
      statistical analysis. The new bronchoaveolar lavage was used to establish
      intrapulmonary pharmacokinetic (PK) model in swine. The pharmacokinetic (PK)
      parameters of tilmicosin, both in pulmonary epithelial lining fluid (PELF) and in
      plasma, were determined using high performance liquid chromatography method and
      WinNonlin software. The pharmacodynamic cutoff (COPD) was calculated using Monte
      Carlo simulation. Our results showed that 100% of WT isolates were covered when
      the ECV was set at 16 MUg/mL. The tilmicosin had concentration-dependent activity
      against H. parasuis. The PK data indicated that tilmicosin concentrations in PELF
      was rapidly increased to high levels at 4 h and kept stable until 48 h after drug
      administration, while the tilmicosin concentration in plasma reached maximum
      levels at 4 h and continued to decrease during 4-72 h. Using Monte Carlo
      simulation, COPD was defined as 1 MUg/mL. Conclusively, the ECV and COPD of
      tilmicosin against H. parasuis were established for the first time based on the
      MIC distribution and PK-PD analysis in the target tissue, respectively. These
      values are of great importance for detection of tilmicosin-resistant H. parasuis
      and for effective treatment of clinical intrapulmonary infection caused by H.
      parasuis. 

PMID- 27047488
TI  - B Cell Development in the Bone Marrow Is Regulated by Homeostatic Feedback
      Exerted by Mature B Cells.
AB  - Cellular homeostasis in the B cell compartment is strictly imposed to balance
      cell production and cell loss. However, it is not clear whether B cell
      development in the bone marrow is an autonomous process or subjected to
      regulation by the peripheral B cell compartment. To specifically address this
      question, we used mice transgenic for human CD20, where effective depletion of B
      lineage cells is obtained upon administration of mouse anti-human CD20
      antibodies, in the absence of any effect on other cell lineages and/or tissues.
      We followed the kinetics of B cell return to equilibrium by BrdU labeling and
      flow cytometry and analyzed the resulting data by mathematical modeling. Labeling
      was much faster in depleted mice. Compared to control mice, B cell-depleted mice
      exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher
      cell death and lower differentiation in the immature B cell compartment. We
      validated the first result by analysis of the expression of Ki67, the nuclear
      protein expressed in proliferating cells, and the second using Annexin V
      staining. Collectively, our results suggest that B lymphopoiesis is subjected to
      homeostatic feedback mechanisms imposed by mature B cells in the peripheral
      compartment. 

PMID- 27047489
TI  - Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication
      for Allotransplantation.
AB  - Being able to track donor reactive T cells during the course of organ
      transplantation is a key to improve the graft survival, to prevent graft
      dysfunction, and to adapt the immunosuppressive regimen. The attempts of
      transplant immunologists have been for long hampered by the large size of the
      alloreactive T cell repertoire. Understanding how self-TCR can interact with
      allogeneic MHC is a key to critically appraise the different assays available to
      analyze the TCR Vbeta repertoire usage. In this report, we will review
      conceptually and experimentally the process of cross-reactivity. We will then
      highlight what can be learned from allotransplantation, a situation of artificial
      cross-reactivity. Finally, the low- and high-resolution techniques to
      characterize the TCR Vbeta repertoire usage in transplantation will be critically
      discussed. 

PMID- 27047490
TI  - Synergy between Common gamma Chain Family Cytokines and IL-18 Potentiates Innate
      and Adaptive Pathways of NK Cell Activation.
AB  - Studies to develop cell-based therapies for cancer and other diseases have
      consistently shown that purified human natural killer (NK) cells secrete
      cytokines and kill target cells after in vitro culture with high concentrations
      of cytokines. However, these assays poorly reflect the conditions that are likely
      to prevail in vivo in the early stages of an infection and have been carried out
      in a wide variety of experimental systems, which has led to contradictions within
      the literature. We have conducted a detailed kinetic and dose-response analysis
      of human NK cell responses to low concentrations of IL-12, IL-15, IL-18, IL-21,
      and IFN-alpha, alone and in combination, and their potential to synergize with IL
      2. We find that very low concentrations of both innate and adaptive common gamma
      chain cytokines synergize with equally low concentrations of IL-18 to drive rapid
      and potent NK cell CD25 and IFN-gamma expression; IL-18 and IL-2 reciprocally
      sustain CD25 and IL-18Ralpha expression in a positive feedback loop; and IL-18
      synergizes with FcgammaRIII (CD16) signaling to augment antibody-dependent
      cellular cytotoxicity. These data indicate that NK cells can be rapidly activated
      by very low doses of innate cytokines and that the common gamma chain cytokines
      have overlapping but distinct functions in combination with IL-18. Importantly,
      synergy between multiple signaling pathways leading to rapid NK cell activation
      at very low cytokine concentrations has been overlooked in prior studies focusing
      on single cytokines or simple combinations. Moreover, although the precise common
      gamma chain cytokines available during primary and secondary infections may
      differ, their synergy with both IL-18 and antigen-antibody immune complexes
      underscores their contribution to NK cell activation during innate and adaptive
      responses. IL-18 signaling potentiates NK cell effector function during innate
      and adaptive immune responses by synergy with IL-2, IL-15, and IL-21 and immune
      complexes. 

PMID- 27047492
TI  - Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity
      CD16 and CCR7 Augments Rituximab-Induced ADCC against Lymphoma and Targets NK
      Cell Migration toward the Lymph Node-Associated Chemokine CCL19.
AB  - For more than a decade, investigators have pursued methods to genetically
      engineer natural killer (NK) cells for use in clinical therapy against cancer.
      Despite considerable advances in viral transduction of hematopoietic stem cells
      and T cells, transduction efficiencies for NK cells have remained disappointingly
      low. Here, we show that NK cells can be genetically reprogramed efficiently using
      a cGMP-compliant mRNA electroporation method that induces rapid and reproducible
      transgene expression in nearly all transfected cells, without negatively
      influencing their viability, phenotype, and cytotoxic function. To study its
      potential therapeutic application, we used this approach to improve key aspects
      involved in efficient lymphoma targeting by adoptively infused ex vivo-expanded
      NK cells. Electroporation of NK cells with mRNA coding for the chemokine receptor
      CCR7 significantly promoted migration toward the lymph node-associated chemokine
      CCL19. Further, introduction of mRNA coding for the high-affinity antibody
      binding receptor CD16 (CD16-158V) substantially augmented NK cell cytotoxicity
      against rituximab-coated lymphoma cells. Based on these data, we conclude that
      this approach can be utilized to genetically modify multiple modalities of NK
      cells in a highly efficient manner with the potential to improve multiple facets
      of their in vivo tumor targeting, thus, opening a new arena for the development
      of more efficacious adoptive NK cell-based cancer immunotherapies. 

PMID- 27047491
TI  - ILC1s in Tissue Inflammation and Infection.
AB  - Innate lymphoid cells (ILCs) are innate immune cells that provide an early source
      of cytokines to initiate and tailor the immune response to the type of the
      encountered pathogen or insult. The group 1 ILCs are comprised of conventional
      natural killer (cNK) cells and subsets of "unconventional NK cells," termed
      ILC1s. Although cNK cells and ILC1s share many features, such as certain
      phenotypic markers and the ability to produce IFN-gamma upon activation, it is
      now becoming apparent that these two subsets develop from different progenitors
      and show unique tissue distribution and functional characteristics. Recent
      studies have aimed at elucidating the individual contributions of cNK cells and
      ILC1s during protective host responses as well as during chronic inflammation.
      This review provides an overview of the current knowledge of the developmental
      origins as well as of the phenotypic and functional characteristics of ILC1s. 

PMID- 27047493
TI  - The Homophilic Domain - An Immunological Archetype.
AB  - The homophilic potential emerges as an important biological principle to boost
      the potency of immunoglobulins. Since homophilic antibodies in human and mouse
      sera exist prior environmental exposure, they are part of the natural antibody
      repertoire. Nevertheless, hemophilic properties are also identified in induced
      antibody repertoire. The use of homophilicity of antibodies in the adaptive
      immunity signifies an archetypic antibody structure. The unique feature of
      homophilicity in the antibody repertoire also highlights an important mechanism
      to boost the antibody potency to protect against infection and atherosclerosis as
      well to treat cancer patients. 

PMID- 27047495
TI  - Expansion of B-1a Cells with Germline Heavy Chain Sequence in Lupus Mice.
AB  - B6.Sle1.Sle2.Sle3 (B6.TC) lupus-prone mice carrying the NZB allele of Cdkn2c,
      encoding for the cyclin-dependent kinase inhibitor P18(INK4), accumulate B-1a
      cells due to a higher rate of proliferative self-renewal. However, it is unclear
      whether this affects primarily early-appearing B-1a cells of fetal origin or
      later-appearing B-1a cells that emerge from bone marrow. B-1a cells are the major
      source of natural autoantibodies, and it has been shown that their protective
      nature is associated with a germline-like sequence, which is characterized by few
      N-nucleotide insertions and a repertoire skewed toward rearrangements
      predominated during fetal life, VH11 and VH12. To determine the nature of B-1a
      cells expanded in B6.TC mice, we amplified immunoglobulin genes by PCR from
      single cells in mice. Sequencing showed a significantly higher proportion of B-1a
      cell antibodies that display fewer N-additions in B6.TC mice than in B6 control
      mice. Following this lower number of N-insertions within the CDR-H3 region, the
      B6.TC B-1a cells display shorter CDR-H3 length than B6 B-1a cells. The absence of
      N-additions is a surrogate for fetal origin, as TdT expression starts after birth
      in mice. Therefore, our results suggest that the B-1a cell population is not only
      expanded in autoimmune B6.TC mice but also qualitatively different with the
      majority of cells from fetal origin. Accordingly, our sequencing results also
      demonstrated the overuse of VH11 and VH12 in autoimmune B6.TC mice as compared to
      B6 controls. These results suggest that the development of lupus autoantibodies
      in these mice is coupled with skewing of the B-1a cell repertoire and possible
      retention of protective natural antibodies. 

PMID- 27047494
TI  - Origin, Localization, and Immunoregulatory Properties of Pulmonary Phagocytes in
      Allergic Asthma.
AB  - Allergic asthma is a chronic inflammatory disease of the airways that is driven
      by maladaptive T helper 2 (Th2) and Th17 immune responses against harmless,
      airborne substances. Pulmonary phagocytes represent the first line of defense in
      the lung where they constantly sense the local environment for potential threats.
      They comprise two distinct cell types, i.e., macrophages and dendritic cells (DC)
      that differ in their origins and functions. Alveolar macrophages quickly take up
      most of the inhaled allergens, yet do not deliver their cargo to naive T cells
      sampling in draining lymph nodes. In contrast, pulmonary DCs instruct CD4(+) T
      cells develop into Th2 and Th17 effectors, initiating the maladaptive immune
      responses toward harmless environmental substances observed in allergic
      individuals. Unraveling the mechanisms underlying this mistaken identity of
      harmless, airborne substances by innate immune cells is one of the great
      challenges in asthma research. The identification of different pulmonary DC
      subsets, their role in antigen uptake, migration to the draining lymph nodes, and
      their potential to instruct distinct T cell responses has set the stage to
      unravel this mystery. However, at this point, a detailed understanding of the
      spatiotemporal resolution of DC subset localization, allergen uptake, processing,
      autocrine and paracrine cellular crosstalk, and the humoral factors that define
      the activation status of DCs is still lacking. In addition to DCs, at least two
      distinct macrophage populations have been identified in the lung that are either
      located in the airway/alveolar lumen or in the interstitium. Recent data suggest
      that such populations can exert either pro- or anti-inflammatory functions.
      Similar to the DC subsets, detailed insights into the individual roles of
      alveolar and interstitial macrophages during the different phases of asthma
      development are still missing. Here, we will provide an update on the current
      understanding of the origin, localization, and function of the diverse pulmonary
      antigen-presenting cell subsets, in particular with regard to the development and
      regulation of allergic asthma. While most data are from mouse models of
      experimental asthma, we have also included available human data to judge the
      translational value of the findings obtained in experimental asthma models. 

PMID- 27047496
TI  - Melatonin Improved Anthocyanin Accumulation by Regulating Gene Expressions and
      Resulted in High Reactive Oxygen Species Scavenging Capacity in Cabbage.
AB  - In this work, we found, that exogenous melatonin pretreatment improved
      anthocyanin accumulation (1- to 2-fold) in cabbage. To verify the relationship
      with melatonin and anthocyanin, an Arabidopsis mutant, snat, which expresses a
      defective form of the melatonin biosynthesis enzyme SNAT (Serotonin N-acetyl
      transferase), was employed. Under cold conditions, the foliage of wild-type
      Arabidopsis exhibited a deeper red color than the snat mutant. This finding
      further proved, that exogenous melatonin treatment was able to affect anthocyanin
      accumulation. To gain a better understanding of how exogenous melatonin
      upregulates anthocyanin, we measured gene expression in cabbage samples treated
      with melatonin and untreated controls. We found that the transcript levels of
      anthocyanin biosynthetic genes were upregulated by melatonin treatment. Moreover,
      melatonin treatment increased the expression levels of the transcription factors
      MYB, bHLH, and WD40, which constitute the transcriptional activation complex
      responsible for coordinative regulation of anthocyanin biosynthetic genes. We
      found, that free radical generation was downregulated, whereas the osmotic
      adjustment and antioxidant capacities were upregulated in exogenous melatonin
      treated cabbage plants. We concluded, that melatonin increases anthocyanin
      production and benefits cabbage growth. 

PMID- 27047497
TI  - Nitrogen-Deficiency Stress Induces Protein Expression Differentially in Low-N
      Tolerant and Low-N Sensitive Maize Genotypes.
AB  - Nitrogen (N) is essential for proper plant growth and its application has proven
      to be critical for agricultural produce. However, for unavoidable economic and
      environmental problems associated with excessive use of N-fertilizers, it is an
      urgent demand to manage application of fertilizers. Improving the N-use
      efficiency (NUE) of crop plants to sustain productivity even at low N levels is
      the possible solution. In the present investigation, contrasting low-N sensitive
      (HM-4) and low-N tolerant (PEHM-2) genotypes were identified and used for
      comparative proteome-profiling of leaves under optimum and low N as well as
      restoration of low N on 3rd (NR3) and 5th (NR5) days after re-supplying N. The
      analysis of differential expression pattern of proteins was performed by 2-D gel
      electrophoresis. Significant variations in the expression of proteins were
      observed under low N, which were genotype specific. In the leaf proteome, 25
      spots were influenced by N treatment and four spots were different between the
      two genotypes. Most of the proteins that were differentially accumulated in
      response to N level and were involved in photosynthesis and metabolism, affirming
      the relationship between N and carbon metabolism. In addition to this, greater
      intensity of some defense proteins in the low N tolerant genotype was found that
      may have a possible role in imparting it tolerance under N starvation conditions.
      The new insights generated on maize proteome in response to N-starvation and
      restoration would be useful toward improvement of NUE in maize. 

PMID- 27047498
TI  - Identification and Comparative Analysis of H2O2-Scavenging Enzymes (Ascorbate
      Peroxidase and Glutathione Peroxidase) in Selected Plants Employing
      Bioinformatics Approaches.
AB  - Among major reactive oxygen species (ROS), hydrogen peroxide (H2O2) exhibits dual
      roles in plant metabolism. Low levels of H2O2 modulate many
      biological/physiological processes in plants; whereas, its high level can cause
      damage to cell structures, having severe consequences. Thus, steady-state level
      of cellular H2O2 must be tightly regulated. Glutathione peroxidases (GPX) and
      ascorbate peroxidase (APX) are two major ROS-scavenging enzymes which catalyze
      the reduction of H2O2 in order to prevent potential H2O2-derived cellular damage.
      Employing bioinformatics approaches, this study presents a comparative evaluation
      of both GPX and APX in 18 different plant species, and provides valuable insights
      into the nature and complex regulation of these enzymes. Herein, (a) potential
      GPX and APX genes/proteins from 18 different plant species were identified, (b)
      their exon/intron organization were analyzed, (c) detailed information about
      their physicochemical properties were provided, (d) conserved motif signatures of
      GPX and APX were identified, (e) their phylogenetic trees and 3D models were
      constructed, (f) protein-protein interaction networks were generated, and finally
      (g) GPX and APX gene expression profiles were analyzed. Study outcomes
      enlightened GPX and APX as major H2O2-scavenging enzymes at their structural and
      functional levels, which could be used in future studies in the current
      direction. 

PMID- 27047499
TI  - Genome-Wide Scans for Delineation of Candidate Genes Regulating Seed-Protein
      Content in Chickpea.
AB  - Identification of potential genes/alleles governing complex seed-protein content
      (SPC) is essential in marker-assisted breeding for quality trait improvement of
      chickpea. Henceforth, the present study utilized an integrated genomics-assisted
      breeding strategy encompassing trait association analysis, selective genotyping
      in traditional bi-parental mapping population and differential expression
      profiling for the first-time to understand the complex genetic architecture of
      quantitative SPC trait in chickpea. For GWAS (genome-wide association study),
      high-throughput genotyping information of 16376 genome-based SNPs (single
      nucleotide polymorphism) discovered from a structured population of 336 sequenced
      desi and kabuli accessions [with 150-200 kb LD (linkage disequilibrium) decay]
      was utilized. This led to identification of seven most effective genomic loci
      (genes) associated [10-20% with 41% combined PVE (phenotypic variation
      explained)] with SPC trait in chickpea. Regardless of the diverse desi and kabuli
      genetic backgrounds, a comparable level of association potential of the
      identified seven genomic loci with SPC trait was observed. Five SPC-associated
      genes were validated successfully in parental accessions and homozygous
      individuals of an intra-specific desi RIL (recombinant inbred line) mapping
      population (ICC 12299 * ICC 4958) by selective genotyping. The seed-specific
      expression, including differential up-regulation (>four fold) of six SPC
      associated genes particularly in accessions, parents and homozygous individuals
      of the aforementioned mapping population with a high level of contrasting SPC (21
      22%) was evident. Collectively, the integrated genomic approach delineated
      diverse naturally occurring novel functional SNP allelic variants in six
      potential candidate genes regulating SPC trait in chickpea. Of these, a non
      synonymous SNP allele-carrying zinc finger transcription factor gene exhibiting
      strong association with SPC trait was found to be the most promising in chickpea.
      The informative functionally relevant molecular tags scaled-down essentially have
      potential to accelerate marker-assisted genetic improvement by developing
      nutritionally rich chickpea cultivars with enhanced SPC. 

PMID- 27047500
TI  - High Quality Maize Centromere 10 Sequence Reveals Evidence of Frequent
      Recombination Events.
AB  - The ancestral centromeres of maize contain long stretches of the tandemly
      arranged CentC repeat. The abundance of tandem DNA repeats and centromeric
      retrotransposons (CR) has presented a significant challenge to completely
      assembling centromeres using traditional sequencing methods. Here, we report a
      nearly complete assembly of the 1.85 Mb maize centromere 10 from inbred B73 using
      PacBio technology and BACs from the reference genome project. The error rates
      estimated from overlapping BAC sequences are 7 * 10(-6) and 5 * 10(-5) for
      mismatches and indels, respectively. The number of gaps in the region covered by
      the reassembly was reduced from 140 in the reference genome to three. Three
      expressed genes are located between 92 and 477 kb from the inferred ancestral
      CentC cluster, which lies within the region of highest centromeric repeat
      density. The improved assembly increased the count of full-length CR from 5 to 55
      and revealed a 22.7 kb segmental duplication that occurred approximately 121,000
      years ago. Our analysis provides evidence of frequent recombination events in the
      form of partial retrotransposons, deletions within retrotransposons, chimeric
      retrotransposons, segmental duplications including higher order CentC repeats, a
      deleted CentC monomer, centromere-proximal inversions, and insertion of
      mitochondrial sequences. Double-strand DNA break (DSB) repair is the most
      plausible mechanism for these events and may be the major driver of centromere
      repeat evolution and diversity. In many cases examined here, DSB repair appears
      to be mediated by microhomology, suggesting that tandem repeats may have evolved
      to efficiently repair frequent DSBs in centromeres. 

PMID- 27047501
TI  - Comparative Leaves Transcriptome Analysis Emphasizing on Accumulation of
      Anthocyanins in Brassica: Molecular Regulation and Potential Interaction with
      Photosynthesis.
AB  - The purple leaf pigmentation mainly associated with anthocyanins accumulation is
      common in Brassica but the mechanisms of its production and its potential
      physiological functions are poorly understood. Here, we performed the phenotypic,
      cytological, physiological, and comparative leaves transcriptome analyses of 11
      different varieties belonging to five Brassica species with purple or green
      leaves. We observed that the anthocyanin was accumulated in most of vegetative
      tissues in all species and also in reproduction organs of B. carinata.
      Anthocyanin accumulated in different part of purple leaves including adaxial and
      abaxial epidermal cells as well as palisade and spongy mesophyll cells. Leave
      transcriptome analysis showed that almost all late biosynthetic genes (LBGs) of
      anthocyanin, especially Dihydroflavonol 4-Reductase (DFR), Anthocyanidin Synthase
      (ANS) and Transparent Testa 19 (TT19), were highly up-regulated in all purple
      leaves. However, only one of transcript factors in anthocyanin biosynthesis
      pathway, Transparent Testa 8 (TT8), was up regulated along with those genes in
      all purple leaves, indicating its pivotal role for anthocyanin production in
      Brassica. Interestingly, with the up-regulation of genes for anthocyanin
      synthesis, Cytosolic 6-phosphogluconolactonase (PLG5) which involved in the
      oxidative pentose-phosphate pathway was up-regulated in all purple leaves and
      three genes FTSH PROTEASE 8 (FTS8), GLYCOLATE OXIDASE 1 (GOX1), and GLUTAMINE
      SYNTHETASE 1;4 (GLN1;4) related to degradation of photo-damaged proteins in
      photosystem II and light respiration were down-regulated. These results
      highlighted the potential physiological functions of anthocyanin accumulation
      related to photosynthesis which might be of great worth in future. 

PMID- 27047502
TI  - A Novel R2R3-MYB Transcription Factor BpMYB106 of Birch (Betula platyphylla)
      Confers Increased Photosynthesis and Growth Rate through Up-regulating
      Photosynthetic Gene Expression.
AB  - We isolated a R2R3-MYB transcription factor BpMYB106, which regulates
      photosynthesis in birch (Betula platyphylla Suk.). BpMYB106 mainly expresses in
      the leaf and shoot tip of birch, and its protein is localized in the nucleus. We
      further fused isolated a 1588 bp promoter of BpMYB106 and analyzed it by PLACE,
      which showed some cis-acting elements related to photosynthesis. BpMYB106
      promoter beta-glucuronidase (GUS) reporter fusion studies gene, the result,
      showed the GUS reporter gene in transgenic birch with BpMYB106 promoter showed
      strong activities in shoot tip, cotyledon margins, and mature leaf trichomes. The
      overexpression of BpMYB106 in birch resulted in significantly increased trichome
      density, net photosynthetic rate, and growth rate as compared with the wild-type
      birch. RNA-Seq profiling revealed the upregulation of several photosynthesis
      related genes in the photosynthesis and oxidative phosphorylation pathways in the
      leaves of transgenic plants. Yeast one-hybrid analysis, coupled with transient
      assay in tobacco, revealed that BpMYB106 binds a MYB binding site MYB2 in
      differentially expressed gene promoters. Thus, BpMYB106 may directly activate the
      expression of a range of photosynthesis related genes through interacting with
      the MYB2 element in their promoters. Our study demonstrating the overexpression
      of BpMYB106-a R2R3-MYB transcription factor-upregulates the genes of the
      photosynthesis and oxidative phosphorylation pathways to improve photosynthesis. 

PMID- 27047503
TI  - Editorial: Amino Acids of the Glutamate Family: Functions beyond Primary
      Metabolism.

PMID- 27047504
TI  - A Nucleotide Signature for the Identification of American Ginseng and Its
      Products.
AB  - American ginseng (derived from Panax quinquefolius) is one of the most widely
      used medicinal herbs in the world. Because of its high price and increasing
      demand, there are many adulterants on the market. The proposed internal
      transcribed spacer 2 (ITS2) has been used to identify raw medicinal materials,
      but it is not suitable for the identification of Chinese patent medicine
      ingredients. Therefore, a short barcode for the identification of processed
      American ginseng and its corresponding Chinese patent medicines would be
      profitable. In this study, 94 samples of American ginseng and Asian ginseng were
      collected from all over the world. The ITS2 region was sequenced, and a
      nucleotide signature was developed based on one single nucleotide polymorphism
      (SNP) site unique to American ginseng. The nucleotide signature (atcactcctt
      tgcgggagtc gaggcgg) consists of 27 bases over the length of the ITS2 sequence
      (420 bp). Furthermore, we also designed primer pairs to amplify the nucleotide
      signature; the specific primer pair 4F/4R has been found to be unique to the
      ginseng species and capable of amplifying the nucleotide signatures from Chinese
      patent medicines and decoctions. We used the nucleotide signature method to
      inspect ginseng products in Chinese patent medicines; 24 batches of Chinese
      patent medicine from stores in Beijing were amplified and sequenced successfully.
      Using the double peaks at the SNP sites of the nucleotide signature, 5 batches
      were found to be counterfeits, and 2 batches were found to contain adulterants.
      Thus, this nucleotide signature, with only 27 bp, has broadened the application
      of DNA barcoding in identification of decoctions, Chinese patent medicines and
      other ginseng products with degraded DNA. This method can rapidly identify
      ginseng products and could also be developed as an on-site detection method. 

PMID- 27047505
TI  - Genome-Wide Identification and Expression Analysis of the 14-3-3 Family Genes in
      Medicago truncatula.
AB  - The 14-3-3 gene family, which is conserved in eukaryotes, is involved in protein
      protein interactions and mediates signal transduction. However, detailed
      investigations of the 14-3-3 gene family in Medicago truncatula are largely
      unknown. In this study, the identification and study of M. truncatula 14-3-3
      family genes were performed based on the latest M. truncatula genome. In the M.
      truncatula genome, 10 14-3-3 family genes were identified, and they can be
      grouped into epsilon and non-epsilon groups. An exon-intron analysis showed that
      the gene structures are conserved in the same group. The protein structure
      analysis showed that 14-3-3 proteins in M. truncatula are composed of nine
      typical antiparallel alpha-helices. The expression patterns of Mt14-3-3 genes
      indicated that they are expressed in all tissues. Furthermore, the gene
      expression levels of Mt14-3-3 under hormone treatment and Sinorhizobium meliloti
      infection showed that the Mt14-3-3 genes were involve in nodule formation. Our
      findings lay a solid foundation for further functional studies of 14-3-3 in M.
      truncatula. 

PMID- 27047506
TI  - Belowground Ecology of Scarabs Feeding on Grass Roots: Current Knowledge and
      Future Directions for Management in Australasia.
AB  - Many scarab beetles spend the majority of their lives belowground as larvae,
      feeding on grass roots. Many of these larvae are significant pests, causing
      damage to crops and grasslands. Damage by larvae of the greyback cane beetle
      (Dermolepida albohirtum), for example, can cause financial losses of up to AU$40
      million annually to the Australian sugarcane industry. We review the ecology of
      some scarab larvae in Australasia, focusing on three subfamilies; Dynastinae,
      Rutelinae, and Melolonthinae, containing key pest species. Although considerable
      research on the control of some scarab pests has been carried out in Australasia,
      for some species, the basic biology and ecology remains largely unexplored. We
      synthesize what is known about these scarab larvae and outline key knowledge gaps
      to highlight future research directions with a view to improve pest management.
      We do this by presenting an overview of the scarab larval host plants and feeding
      behavior; the impacts of abiotic (temperature, moisture, and fertilization) and
      biotic (pathogens, natural enemies, and microbial symbionts) factors on scarab
      larvae and conclude with how abiotic and biotic factors can be applied in
      agriculture for improved pest management, suggesting future research directions.
      Several host plant microbial symbionts, such as arbuscular mycorrhizal fungi and
      endophytes, can improve plant tolerance to scarabs and reduce larval performance,
      which have shown promise for use in pest management. In addition to this, several
      microbial scarab pathogens have been isolated for commercial use in pest
      management with particularly promising results. The entomopathogenic fungus
      Metarhizium anisopliae caused a 50% reduction in cane beetle larvae while natural
      enemies such as entomopathogenic nematodes have also shown potential as a
      biocontrol. Key abiotic factors, such as soil water, play an important role in
      affecting both scarab larvae and these control agents and should therefore
      feature in future multi-factorial experiments. Continued research should focus on
      filling knowledge gaps including host plant preferences, attractive trap crops,
      and naturally occurring pathogens that are locally adapted, to achieve high
      efficacy in the field. 

PMID- 27047507
TI  - The Black-Box of Plant Apoplast Lipidomes.

PMID- 27047508
TI  - Soybean C2H2-Type Zinc Finger Protein GmZFP3 with Conserved QALGGH Motif
      Negatively Regulates Drought Responses in Transgenic Arabidopsis.
AB  - Plant response to environmental stresses is regulated by a complicated network of
      regulatory and functional genes. In this study, we isolated the putative stress
      associated gene GmZFP3 (a C2H2-type Zinc finger protein gene) based on the
      previous finding that it was one of two genes located in the QTL region between
      the Satt590 and Satt567 markers related to soybean tolerance to drought. Temporal
      and spatial expression analysis using quantitative real-time PCR indicated that
      GmZFP3 was primarily expressed in roots, stems and leaf organs and was expressed
      at low levels in flowers and soybean pods. Moreover, GmZFP3 expression increased
      in response to polyethylene glycol (PEG) and Abscisic acid (ABA) treatments. In
      addition, subcellular localization analysis indicated that GmZFP3 was
      ubiquitously distributed in plant cells. Transgenic experiments indicated that
      GmZFP3 played a negative role in plant tolerance to drought. Analysis of ABA
      related marker gene expression in Arabidopsis suggested that GmZFP3 might be
      involved in the ABA-dependent pathway during the drought stress response. Taken
      together, these results suggest that soybean GmZFP3 negatively regulates the
      drought response. 

PMID- 27047509
TI  - Activation of Shikimate, Phenylpropanoid, Oxylipins, and Auxin Pathways in
      Pectobacterium carotovorum Elicitors-Treated Moss.
AB  - Plants have developed complex defense mechanisms to cope with microbial
      pathogens. Pathogen-associated molecular patterns (PAMPs) and damage-associated
      molecular patterns (DAMPs) are perceived by pattern recognition receptors (PRRs),
      leading to the activation of defense. While substantial progress has been made in
      understanding the activation of plant defense by PAMPs and DAMPs recognition in
      tracheophytes, far less information exists on related processes in early
      divergent plants like mosses. The aim of this study was to identify genes that
      were induced in P. patens in response to elicitors of Pectobacterium carotovorum
      subsp. carotovorum, using a cDNA suppression subtractive hybridization (SSH)
      method. A total of 239 unigenes were identified, including genes involved in
      defense responses related to the shikimate, phenylpropanoid, and oxylipin
      pathways. The expression levels of selected genes related to these pathways were
      analyzed using quantitative RT-PCR, confirming their rapid induction by P.c.
      carotovorum derived elicitors. In addition, P. patens induced cell wall
      reinforcement after elicitor treatment by incorporation of phenolic compounds,
      callose deposition, and elevated expression of Dirigent-like encoding genes.
      Small molecule defense markers and phytohormones such as cinnamic acid, 12-oxo
      phytodienoic acid, and auxin levels all increased in elicitor-treated moss
      tissues. In contrast, salicylic acid levels decreased while abscisic acid levels
      remained unchanged. P. patens reporter lines harboring an auxin-inducible
      promoter fused to beta-glucuronidase revealed GUS activity in protonemal and
      gametophores tissues treated with elicitors of P.c. carotovorum, consistent with
      a localized activation of auxin signaling. These results indicate that P. patens
      activates the shikimate, phenylpropanoid, oxylipins, and auxin pathways upon
      treatment with P.c. carotovorum derived elicitors. 

PMID- 27047511
TI  - Male and Female Subpopulations of Salix viminalis Present High Genetic Diversity
      and High Long-Term Migration Rates between Them.
AB  - Dioecy distributed in 157 flowering plant families and 959 flowering plant
      genera. Morphological and physiological differences between male and female
      plants have been studied extensively, but studies of sex-specific genetic
      diversity are relatively scarce in dioecious plants. In this study, 20 SSR loci
      were employed to examine the genetic variance of male subpopulations and female
      subpopulations in Salix viminalis. The results showed that all of the markers
      were polymorphic (Na = 14.15, He = 0.7566) and workable to reveal the genetic
      diversity of S. viminalis. No statistically significant difference was detected
      between male and female subpopulations, but the average genetic diversity of male
      subpopulations (Na = 7.12, He = 0.7071) and female subpopulations (Na = 7.31, He
      = 0.7226) were high. Under unfavorable environments (West Liao basin), the
      genetic diversity between male and female subpopulations was still not
      significantly different, but the genetic diversity of sexual subpopulations were
      lower. The differentiation of the ten subpopulations in S. viminalis was moderate
      (FST = 0.0858), which was conformed by AMOVA that most of genetic variance (94%)
      existed within subpopulations. Pairwise FST indicated no differentiation between
      sexual subpopulations, which was accompanied by high long-term migrate between
      them (M = 0.73~1.26). However, little recent migration was found between sexual
      subpopulations. Therefore, artificial crossing or/and transplantation by cutting
      propagation should be carried out so as to increase the migration during the
      process of ex situ conservation. 

PMID- 27047510
TI  - Molecular Farming in Artemisia annua, a Promising Approach to Improve Anti
      malarial Drug Production.
AB  - Malaria is a parasite infection affecting millions of people worldwide. Even
      though progress has been made in prevention and treatment of the disease; an
      estimated 214 million cases of malaria occurred in 2015, resulting in 438,000
      estimated deaths; most of them occurring in Africa among children under the age
      of five. This article aims to review the epidemiology, future risk factors and
      current treatments of malaria, with particular focus on the promising potential
      of molecular farming that uses metabolic engineering in plants as an effective
      anti-malarial solution. Malaria represents an example of how a health problem
      may, on one hand, influence the proper development of a country, due to its
      burden of the disease. On the other hand, it constitutes an opportunity for
      lucrative business of diverse stakeholders. In contrast, plant biofarming is
      proposed here as a sustainable, promising, alternative for the production, not
      only of natural herbal repellents for malaria prevention but also for the
      production of sustainable anti-malarial drugs, like artemisinin (AN), used for
      primary parasite infection treatments. AN, a sesquiterpene lactone, is a natural
      anti-malarial compound that can be found in Artemisia annua. However, the low
      concentration of AN in the plant makes this molecule relatively expensive and
      difficult to produce in order to meet the current worldwide demand of Artemisinin
      Combination Therapies (ACTs), especially for economically disadvantaged people in
      developing countries. The biosynthetic pathway of AN, a process that takes place
      only in glandular secretory trichomes of A. annua, is relatively well elucidated.
      Significant efforts have been made using plant genetic engineering to increase
      production of this compound. These include diverse genetic manipulation
      approaches, such as studies on diverse transcription factors which have been
      shown to regulate the AN genetic pathway and other biological processes. Results
      look promising; however, further efforts should be addressed toward optimization
      of the most cost-effective biofarming approaches for synthesis and production of
      medicines against the malaria parasite. 

PMID- 27047512
TI  - Association Mapping for Fiber-Related Traits and Digestibility in Alfalfa
      (Medicago sativa).
AB  - Association mapping is a powerful approach for exploring the molecular genetic
      basis of complex quantitative traits. An alfalfa (Medicago sativa) association
      panel comprised of 336 genotypes from 75 alfalfa accessions represented by four
      to eight genotypes for each accession. Each genotype was genotyped using 85
      simple sequence repeat (SSR) markers and phenotyped for five fiber-related traits
      in four different environments. A model-based structure analysis was used to
      group all genotypes into two groups. Most of the genotypes have a low relative
      kinship (<0.3), suggesting population stratification not be an issue for
      association analysis. Generally, the Q + K model exhibited the best performance
      to eliminate the false associated positives. In total, 124 marker-trait
      associations were predicted (p < 0.005). Among these, eight associations were
      predicted in two environments repeatedly and 20 markers were predicted to be
      associated with multiple traits. These trait-associated markers will greatly help
      marker-assisted breeding programs to improve fiber-related quality traits in
      alfalfa. 

PMID- 27047513
TI  - De novo Sequencing of the Leaf Transcriptome Reveals Complex Light-Responsive
      Regulatory Networks in Camellia sinensis cv. Baijiguan.
AB  - Tea plants (Camellia sinensis L.) possess high genetic diversity that is
      important for breeding. One cultivar, Baijiguan, exhibits a yellow leaf
      phenotype, reduced chlorophyll (Chl) content, and aberrant chloroplast structures
      under high light intensity. In contrast, under low light intensity, the flush
      shoot from Baijiguan becomes green, the Chl content increases significantly, and
      the chloroplasts exhibit normal structures. To understand the underlying
      molecular mechanisms for these observations, we performed de novo transcriptome
      sequencing and digital gene expression (DGE) profiling using Illumina sequencing
      technology. De novo transcriptome assembly identified 88,788 unigenes, including
      1652 transcription factors from 25 families. In total, 1993 and 2576
      differentially expressed genes (DEGs) were identified in Baijiguan plants treated
      with 3 and 6 days of shade, respectively. Gene Ontology (GO) and pathway
      enrichment analyses indicated that the DEGs are predominantly involved in the ROS
      scavenging system, chloroplast development, photosynthetic pigment synthesis,
      secondary metabolism, and circadian systems. The light-responsive gene POR
      (protochlorophyllide oxidoreductase) and transcription factor HY5 were
      identified. Quantitative real-time PCR (qRT-PCR) analysis of 20 selected DEGs
      confirmed the RNA-sequencing (RNA-Seq) results. Overall, these findings suggest
      that high light intensity inhibits the expression of photosystem II 10-kDa
      protein (PsbR) in Baijiguan, thus affecting PSII stability, chloroplast
      development and chlorophyll biosynthesis. 

PMID- 27047514
TI  - Enhancing Legume Ecosystem Services through an Understanding of Plant-Pollinator
      Interplay.
AB  - Legumes are bee-pollinated, but to a different extent. The importance of the
      plant-pollinator interplay (PPI), in flowering crops such as legumes lies in a
      combination of the importance of pollination for the production service and
      breeding strategies, plus the increasing urgency in mitigating the decline of
      pollinators through the development and implementation of conservation measures.
      To realize the full potential of the PPI, a multidisciplinary approach is
      required. This article assembles an international team of genebank managers,
      geneticists, plant breeders, experts on environmental governance and agro
      ecology, and comprises several sections. The contributions in these sections
      outline both the state of the art of knowledge in the field and the novel aspects
      under development, and encompass a range of reviews, opinions and perspectives.
      The first three sections explore the role of PPI in legume breeding strategies.
      PPI based approaches to crop improvement can make it possible to adapt and re
      design breeding strategies to meet both goals of: (1) optimal productivity, based
      on an efficient use of pollinators, and (2) biodiversity conservation. The next
      section deals with entomological aspects and focuses on the protection of the
      "pest control service" and pollinators in legume crops. The final section
      addresses general approaches to encourage the synergy between food production and
      pollination services at farmer field level. Two basic approaches are proposed:
      (a) Farming with Alternative Pollinators and (b) Crop Design System. 

PMID- 27047516
TI  - Multiple Impacts of Loss of Plastidic Phosphatidylglycerol Biosynthesis on
      Photosynthesis during Seedling Growth of Arabidopsis.
AB  - Phosphatidylglycerol (PG) is the only major phospholipid in the thylakoid
      membrane in cyanobacteria and plant chloroplasts. Although PG accounts only for
      ~10% of total thylakoid lipids, it plays indispensable roles in oxygenic
      photosynthesis. In contrast to the comprehensive analyses of PG-deprived mutants
      in cyanobacteria, in vivo roles of PG in photosynthesis during plant growth
      remain elusive. In this study, we characterized the photosynthesis of an
      Arabidopsis thaliana T-DNA insertional mutant (pgp1-2), which lacks plastidic PG
      biosynthesis. In the pgp1-2 mutant, energy transfer from antenna pigments to the
      photosystem II (PSII) reaction center was severely impaired, which resulted in
      low photochemical efficiency of PSII. Unlike in the wild type, in pgp1-2, the
      PSII complexes were susceptible to photodamage by red light irradiation.
      Manganese ions were mostly dissociated from protein systems in pgp1-2, with
      oxygen-evolving activity of PSII absent in the mutant thylakoids. The oxygen
      evolving complex may be disrupted in pgp1-2, which may accelerate the photodamage
      to PSII by red light. On the acceptor side of the mutant PSII, decreased electron
      accepting capacity was observed along with impaired electron transfer. Although
      the reaction center of PSI was relatively active in pgp1-2 compared to the severe
      impairment in PSII, the cyclic electron transport was dysfunctional. Chlorophyll
      fluorescence analysis at 77K revealed that PG may not be needed for the self
      organization of the macromolecular protein network in grana thylakoids but is
      essential for the assembly of antenna-reaction center complexes. Our data clearly
      show that thylakoid glycolipids cannot substitute for the role of PG in
      photosynthesis during plant growth. 

PMID- 27047515
TI  - Genome-Wide Single-Nucleotide Polymorphisms Discovery and High-Density Genetic
      Map Construction in Cauliflower Using Specific-Locus Amplified Fragment
      Sequencing.
AB  - Molecular markers and genetic maps play an important role in plant genomics and
      breeding studies. Cauliflower is an important and distinctive vegetable; however,
      very few molecular resources have been reported for this species. In this study,
      a novel, specific-locus amplified fragment (SLAF) sequencing strategy was
      employed for large-scale single nucleotide polymorphism (SNP) discovery and high
      density genetic map construction in a double-haploid, segregating population of
      cauliflower. A total of 12.47 Gb raw data containing 77.92 M pair-end reads were
      obtained after processing and 6815 polymorphic SLAFs between the two parents were
      detected. The average sequencing depths reached 52.66-fold for the female parent
      and 49.35-fold for the male parent. Subsequently, these polymorphic SLAFs were
      used to genotype the population and further filtered based on several criteria to
      construct a genetic linkage map of cauliflower. Finally, 1776 high-quality SLAF
      markers, including 2741 SNPs, constituted the linkage map with average data
      integrity of 95.68%. The final map spanned a total genetic length of 890.01 cM
      with an average marker interval of 0.50 cM, and covered 364.9 Mb of the reference
      genome. The markers and genetic map developed in this study could provide an
      important foundation not only for comparative genomics studies within Brassica
      oleracea species but also for quantitative trait loci identification and
      molecular breeding of cauliflower. 

PMID- 27047517
TI  - Association Mapping of Flowering Time QTLs and Insight into Their Contributions
      to Rapeseed Growth Habits.
AB  - Plants have developed sophisticated systems to adapt to local conditions during
      evolution, domestication and natural or artificial selection. The selective
      pressures of these different growing conditions have caused significant genomic
      divergence within species. The flowering time trait is the most crucial factor
      because it helps plants to maintain sustainable development. Controlling
      flowering at appropriate times can also prevent plants from suffering from
      adverse growth conditions, such as drought, winter hardness, and disease. Hence,
      discovering the genome-wide genetic mechanisms that influence flowering time
      variations and understanding their contributions to adaptation should be a
      central goal of plant genetics and genomics. A global core collection panel with
      448 inbred rapeseed lines was first planted in four independent environments, and
      their flowering time traits were evaluated. We then performed a genome-wide
      association mapping of flowering times with a 60 K SNP array for this core
      collection. With quality control and filtration, 20,342 SNP markers were
      ultimately used for further analyses. In total, 312 SNPs showed marker-trait
      associations in all four environments, and they were based on a threshold p-value
      of 4.06 * 10(-4); the 40 QTLs showed significant association with flowering time
      variations. To explore flowering time QTLs and genes related to growth habits in
      rapeseed, selection signals related to divergent habits were screened at the
      genome-wide level and 117 genomic regions were found. Comparing locations of
      flowering time QTLs and genes with these selection regions revealed that 20
      flowering time QTLs and 224 flowering time genes overlapped with 24 and 81
      selected regions, respectively. Based on this study, a number of marker-trait
      associations and candidate genes for flowering time variations in rapeseed were
      revealed. Moreover, we also showed that both flowering time QTLs and genes play
      important roles in rapeseed growth habits. These results will be applied to
      rapeseed breeding programs, and they will aid in our understanding of the
      relation between flowering time variations and growth habits in plants. 

PMID- 27047518
TI  - Editorial: Control of Plant Pathogens by Biogenic Elicitors and Possible
      Mechanisms of Action.

PMID- 27047519
TI  - The Complete Chloroplast Genome Sequence of Ampelopsis: Gene Organization,
      Comparative Analysis, and Phylogenetic Relationships to Other Angiosperms.
AB  - Ampelopsis brevipedunculata is an economically important plant that belongs to
      the Vitaceae family of angiosperms. The phylogenetic placement of Vitaceae is
      still unresolved. Recent phylogenetic studies suggested that it should be placed
      in various alternative families including Caryophyllaceae, asteraceae,
      Saxifragaceae, Dilleniaceae, or with the rest of the rosid families. However,
      these analyses provided weak supportive results because they were based on only
      one of several genes. Accordingly, complete chloroplast genome sequences are
      required to resolve the phylogenetic relationships among angiosperms. Recent
      phylogenetic analyses based on the complete chloroplast genome sequence suggested
      strong support for the position of Vitaceae as the earliest diverging lineage of
      rosids and placed it as a sister to the remaining rosids. These studies also
      revealed relationships among several major lineages of angiosperms; however, they
      highlighted the significance of taxon sampling for obtaining accurate
      phylogenies. In the present study, we sequenced the complete chloroplast genome
      of A. brevipedunculata and used these data to assess the relationships among 32
      angiosperms, including 18 taxa of rosids. The Ampelopsis chloroplast genome is
      161,090 bp in length, and includes a pair of inverted repeats of 26,394 bp that
      are separated by small and large single copy regions of 19,036 bp and 89,266 bp,
      respectively. The gene content and order of Ampelopsis is identical to many other
      unrearranged angiosperm chloroplast genomes, including Vitis and tobacco. A
      phylogenetic tree constructed based on 70 protein-coding genes of 33 angiosperms
      showed that both Saxifragales and Vitaceae diverged from the rosid clade and
      formed two clades with 100% bootstrap value. The position of the Vitaceae is
      sister to Saxifragales, and both are the basal and earliest diverging lineages.
      Moreover, Saxifragales forms a sister clade to Vitaceae of rosids. Overall, the
      results of this study will contribute to better support of the evolution,
      molecular biology and genetic improvement of the plant Ampelopsis. 

PMID- 27047520
TI  - BAC-Pool Sequencing and Assembly of 19 Mb of the Complex Sugarcane Genome.
AB  - Sequencing plant genomes are often challenging because of their complex
      architecture and high content of repetitive sequences. Sugarcane has one of the
      most complex genomes. It is highly polyploid, preserves intact homeologous
      chromosomes from its parental species and contains >55% repetitive sequences.
      Although bacterial artificial chromosome (BAC) libraries have emerged as an
      alternative for accessing the sugarcane genome, sequencing individual clones is
      laborious and expensive. Here, we present a strategy for sequencing and assembly
      reads produced from the DNA of pooled BAC clones. A set of 178 BAC clones,
      randomly sampled from the SP80-3280 sugarcane BAC library, was pooled and
      sequenced using the Illumina HiSeq2000 and PacBio platforms. A hybrid assembly
      strategy was used to generate 2,451 scaffolds comprising 19.2 MB of assembled
      genome sequence. Scaffolds of >=20 Kb corresponded to 80% of the assembled
      sequences, and the full sequences of forty BACs were recovered in one or two
      contigs. Alignment of the BAC scaffolds with the chromosome sequences of sorghum
      showed a high degree of collinearity and gene order. The alignment of the BAC
      scaffolds to the 10 sorghum chromosomes suggests that the genome of the SP80-3280
      sugarcane variety is ~19% contracted in relation to the sorghum genome. In
      conclusion, our data show that sequencing pools composed of high numbers of BAC
      clones may help to construct a reference scaffold map of the sugarcane genome. 

PMID- 27047521
TI  - The Response of the Root Apex in Plant Adaptation to Iron Heterogeneity in Soil.
AB  - Iron (Fe) is an essential micronutrient for plant growth and development, and is
      frequently limiting. By contrast, over-accumulation of Fe in plant tissues leads
      to toxicity. In soils, the distribution of Fe is highly heterogeneous. To cope
      with this heterogeneity, plant roots engage an array of adaptive responses to
      adjust their morphology and physiology. In this article, we review root
      morphological and physiological changes in response to low- and high-Fe
      conditions and highlight differences between these responses. We especially focus
      on the role of the root apex in dealing with the stresses resulting from Fe
      shortage and excess. 

PMID- 27047522
TI  - Above-Belowground Herbivore Interactions in Mixed Plant Communities Are
      Influenced by Altered Precipitation Patterns.
AB  - Root- and shoot-feeding herbivores have the capacity to influence one another by
      modifying the chemistry of the shared host plant. This can alter rates of
      nutrient mineralization and uptake by neighboring plants and influence plant
      plant competition, particularly in mixtures combining grasses and legumes. Root
      herbivory-induced exudation of nitrogen (N) from legume roots, for example, may
      increase N acquisition by co-occurring grasses, with knock-on effects on
      grassland community composition. Little is known about how climate change may
      affect these interactions, but an important and timely question is how will grass
      legume mixtures respond in a future with an increasing reliance on legume N
      mineralization in terrestrial ecosystems. Using a model grass-legume mixture,
      this study investigated how simultaneous attack on lucerne (Medicago sativa) by
      belowground weevils (Sitona discoideus) and aboveground aphids (Acyrthosiphon
      pisum) affected a neighboring grass (Phalaris aquatica) when subjected to
      drought, ambient, and elevated precipitation. Feeding on rhizobial nodules by
      weevil larvae enhanced soil water retention under ambient and elevated
      precipitation, but only when aphids were absent. While drought decreased
      nodulation and root N content in lucerne, grass root and shoot chemistry were
      unaffected by changes in precipitation. However, plant communities containing
      weevils but not aphids showed increased grass height and N concentrations, most
      likely associated with the transfer of N from weevil-attacked lucerne plants
      containing more nodules and higher root N concentrations compared with insect
      free plants. Drought decreased aphid abundance by 54% but increased total and
      some specific amino acid concentrations (glycine, lysine, methionine, tyrosine,
      cysteine, histidine, arginine, aspartate, and glutamate), suggesting that aphid
      declines were being driven by other facets of drought (e.g., reduced phloem
      hydraulics). The presence of weevil larvae belowground decreased aphid numbers by
      30%, likely associated with a significant reduction in proline in weevil-treated
      lucerne plants. This study demonstrates how predicted changes to precipitation
      patterns and indirect interactions between herbivores can alter the outcome of
      competition between N-fixing legumes and non-N-fixing grasses, with important
      implications for plant community structure and productivity. 

PMID- 27047523
TI  - Physiological, Anatomical and Metabolic Implications of Salt Tolerance in the
      Halophyte Salvadora persica under Hydroponic Culture Condition.
AB  - Salt tolerance mechanism of an extreme halophyte Salvadora persica was assessed
      by analyzing growth, nutrient uptake, anatomical modifications and alterations in
      levels of some organic metabolites in seedlings imposed to various levels of
      salinity (0, 250, 500, and 750 mM NaCl) under hydroponic culture condition. After
      21 days of salt treatment, plant height, leaf area, and shoot biomass decreased
      with increase in salinity whereas the leaf succulence increased significantly
      with increasing salinity in S. persica. The RWC% of leaf increased progressively
      in salt-treated seedlings as compared to control. Na(+) contents of leaf, stem
      and root increased in dose-dependent manner whereas there was no significant
      changes in K(+) content. There was significant alterations in leaf, stem, and
      root anatomy by salinity. The thickness of epidermis and spongy parenchyma of
      leaf increased in salt treated seedlings as compared to control, whereas palisade
      parenchyma decreased dramatically in extreme salinity (750 mM NaCl). There was a
      significant reduction in stomatal density and stomatal pore area of leaf with
      increasing salinity. Anatomical observations of stem showed that the epidermal
      cells diameter and thickness of cortex decreased by salinity whereas thickness of
      hypodermal layer, diameter of hypodermal cell, pith area and pith cell diameter
      increased by high salinity. The root anatomy showed an increase in epidermal
      thickness by salinity whereas diameters of epidermal cells and xylem vessels
      decreased. Total soluble sugar content remained unchanged at all levels of
      salinity whereas reducing sugar content increased by twofold at high salinity
      (750 mM NaCl). The starch content of leaf decreased progressively in NaCl treated
      seedlings as compared to control. Total free amino acid content did not change at
      low salinity (250 mM), whereas it increased significantly at higher salinity (500
      and 750 mM NaCl). The proline content increased in NaCl treated seedlings as
      compared to control. There was no significant changes in polyphenols level of
      leaf at all levels of salinity. The results from the present study reveal that
      seedlings imposed with various levels of salinity experience physiological,
      biochemical and anatomical modifications in order to circumvent under extreme
      saline environment. The vital mechanisms of salt tolerance in S. persica are
      higher accumulation of organic metabolites, increase in leaf succulency,
      efficient Na(+) sequestration in the vacuole, K(+) retention in the
      photosynthetic tissue and increase in WUE by reducing stomatal density.
      Therefore, S. persica is a potential halophytic species to be cultivated in
      saline lands to eliminate excess salt and make it favorable for agriculture. 

PMID- 27047524
TI  - The Complete Chloroplast Genome Sequences of Three Veroniceae Species
      (Plantaginaceae): Comparative Analysis and Highly Divergent Regions.
AB  - Previous studies of Veronica and related genera were weakly supported by
      molecular and paraphyletic taxa. Here, we report the complete chloroplast genome
      sequence of Veronica nakaiana and the related species Veronica persica and
      Veronicastrum sibiricum. The chloroplast genome length of V. nakaiana, V.
      persica, and V. sibiricum ranged from 150,198 bp to 152,930 bp. A total of 112
      genes comprising 79 protein coding genes, 29 tRNA genes, and 4 rRNA genes were
      observed in three chloroplast genomes. The total number of SSRs was 48, 51, and
      53 in V. nakaiana, V. persica, and V. sibiricum, respectively. Two SSRs (10 bp of
      AT and 12 bp of AATA) were observed in the same regions (rpoC2 and ndhD) in three
      chloroplast genomes. A comparison of coding genes and non-coding regions between
      V. nakaiana and V. persica revealed divergent sites, with the greatest variation
      occurring petD-rpoA region. The complete chloroplast genome sequence information
      regarding the three Veroniceae will be helpful for elucidating Veroniceae
      phylogenetic relationships. 

PMID- 27047525
TI  - Molecular Mechanisms for Vascular Development and Secondary Cell Wall Formation.
AB  - Vascular tissues are important for transporting water and nutrients throughout
      the plant and as physical support of upright growth. The primary constituents of
      vascular tissues, xylem, and phloem, are derived from the meristematic vascular
      procambium and cambium. Xylem cells develop secondary cell walls (SCWs) that form
      the largest part of plant lignocellulosic biomass that serve as a renewable
      feedstock for biofuel production. For the last decade, research on vascular
      development and SCW biosynthesis has seen rapid progress due to the importance of
      these processes to plant biology and to the biofuel industry. Plant hormones,
      transcriptional regulators and peptide signaling regulate procambium/cambium
      proliferation, vascular patterning, and xylem differentiation. Transcriptional
      regulatory pathways play a pivot role in SCW biosynthesis. Although most of these
      discoveries are derived from research in Arabidopsis, many genes have shown
      conserved functions in biofuel feedstock species. Here, we review the recent
      advances in our understanding of vascular development and SCW formation and
      discuss potential biotechnological uses. 

PMID- 27047526
TI  - A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27
      kD gamma-Zein Accumulates to High Levels in the Endoplasmic Reticulum without
      Forming Protein Bodies in Transgenic Tobacco.
AB  - Human Bone Morphogenetic Protein-2 (hBMP2) is an osteoinductive agent
      physiologically involved in bone remodeling processes. A commercialized
      recombinant hBMP2 produced in mammalian cell lines is available in different
      clinical applications where bone regeneration is needed, but widespread use has
      been hindered due to an unfavorable cost/effective ratio. Protein bodies are very
      large insoluble protein polymers that originate within the endoplasmic reticulum
      by prolamine accumulation during the cereal seed development. The N-terminal
      domain of the maize prolamin 27 kD gamma-zein is able to promote protein body
      biogenesis when fused to other proteins. To produce high yield of recombinant
      hBMP2 active domain (ad) in stably transformed tobacco plants we have fused it to
      the gamma-zein domain. We show that this zein-hBMP2ad fusion is retained in the
      endoplasmic reticulum without forming insoluble protein bodies. The accumulation
      levels are above 1% of total soluble leaf proteins, indicating that it could be a
      rapid and suitable strategy to produce hBMP2ad at affordable costs. 

PMID- 27047527
TI  - The DnaJ-Like Zinc Finger Domain Protein PSA2 Affects Light Acclimation and
      Chloroplast Development in Arabidopsis thaliana.
AB  - The biosynthesis of chlorophylls and carotenoids and the assembly of thylakoid
      membranes are critical for the photoautotrophic growth of plants. Different
      factors are involved in these two processes. In recent years, members of the DnaJ
      like zinc finger domain proteins have been found to take part in the biogenesis
      and/or the maintenance of plastids. One member of this family of proteins, PSA2,
      was recently found to localize to the thylakoid lumen and regulate the
      accumulation of photosystem I. In this study, we report that the silencing of
      PSA2 in Arabidopsis thaliana resulted in variegated leaves and retarded growth.
      Although both chlorophylls and total carotenoids decreased in the psa2 mutant,
      violaxanthin, and zeaxanthin accumulated in the mutant seedlings grown under
      growth condition. Lower levels of non-photochemical quenching and electron
      transport rate were also found in the psa2 mutant seedlings under growth
      condition compared with those of the wild-type plants, indicating an impaired
      capability to acclimate to normal light irradiance when PSA2 was silenced.
      Moreover, we also observed an abnormal assembly of grana thylakoids and poorly
      developed stroma thylakoids in psa2 chloroplasts. Taken together, our results
      demonstrate that PSA2 is a member of the DnaJ-like zinc finger domain protein
      family that affects light acclimation and chloroplast development. 

PMID- 27047528
TI  - The Mechanism of Ethylene Signaling Induced by Endophytic Fungus Gilmaniella sp.
      AL12 Mediating Sesquiterpenoids Biosynthesis in Atractylodes lancea.
AB  - Ethylene, the first known gaseous phytohormone, is involved in plant growth,
      development as well as responses to environmental signals. However, limited
      information is available on the role of ethylene in endophytic fungi induced
      secondary metabolites biosynthesis. Atractylodes lancea is a traditional Chinese
      herb, and its quality depends on the main active compounds sesquiterpenoids. This
      work showed that the endophytic fungus Gilmaniella sp. AL12 induced ethylene
      production in Atractylodes lancea. Pre-treatment of plantlets with ethylene
      inhibiter aminooxyacetic acid (AOA) suppressed endophytic fungi induced
      accumulation of ethylene and sesquiterpenoids. Plantlets were further treated
      with AOA, salicylic acid (SA) biosynthesis inhibitor paclobutrazol (PAC),
      jasmonic acid inhibitor ibuprofen (IBU), hydrogen peroxide (H2O2) scavenger
      catalase (CAT), nitric oxide (NO)-specific scavenger 2-(4-Carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO). With endophytic
      fungi inoculation, IBU or PAC did not inhibit ethylene production, and JA and SA
      generation were suppressed by AOA, showing that ethylene may act as an upstream
      signal of JA and SA pathway. With endophytic fungi inoculation, CAT or cPTIO
      suppressed ethylene production, and H2O2 or NO generation was not affected by 1
      aminocyclopropane-1-carboxylic acid (ACC), showing that ethylene may act as a
      downstream signal of H2O2 and NO pathway. Then, plantlets were treated with
      ethylene donor ACC, JA, SA, H2O2, NO donor sodium nitroprusside (SNP). Exogenous
      ACC could trigger JA and SA generation, whereas exogenous JA or SA did not affect
      ethylene production, and the induced sesquiterpenoids accumulation triggered by
      ACC was partly suppressed by IBU and PAC, showing that ethylene acted as an
      upstream signal of JA and SA pathway. Exogenous ACC did not affect H2O2 or NO
      generation, whereas exogenous H2O2 and SNP induced ethylene production, and the
      induced sesquiterpenoids accumulation triggered by SNP or H2O2 was partly
      suppressed by ACC, showing that ethylene acted as a downstream signal of NO and
      H2O2 pathway. Taken together, this study demonstrated that ethylene is an
      upstream signal of JA and SA, and a downstream signal of NO and H2O2 signaling
      pathways, and acts as an important signal mediating sesquiterpenoids biosynthesis
      of Atractylodes lancea induced by the endophytic fungus. 

PMID- 27047529
TI  - Corrigendum: Flux balance analysis reveals acetate metabolism modulates cyclic
      electron flow and alternative glycolytic pathways in Chlamydomonas reinhardtii.
AB  - [This corrects the article on p. 474 in vol. 6, PMID: 26175742.]. 

PMID- 27047530
TI  - Establishing Wildflower Pollinator Habitats in Agricultural Farmland to Provide
      Multiple Ecosystem Services.

PMID- 27047531
TI  - The Role of the Atypical Kinases ABC1K7 and ABC1K8 in Abscisic Acid Responses.
AB  - The ABC1K family of atypical kinases (activity of bc1 complex kinase) is
      represented in bacteria, archaea, and eukaryotes. In plants they regulate diverse
      physiological processes in the chloroplasts and mitochondria, but their precise
      functions are poorly defined. ABC1K7 and ABC1K8 are probably involved in
      oxidative stress responses, isoprenyl lipid synthesis and distribution of iron
      within chloroplasts. Because reactive oxygen species take part in abscisic acid
      (ABA)-mediated processes, we investigated the functions of ABC1K7 and ABC1K8
      during germination, stomatal movement, and leaf senescence. Both genes were
      upregulated by ABA treatment and some ABA-responsive physiological processes were
      affected in abc1k7 and abc1k8 mutants. Germination was more severely affected by
      ABA, osmotic stress and salt stress in the single and double mutants; the
      stomatal aperture was smaller in the mutants under standard growth conditions and
      was not further reduced by exogenous ABA application; ABA-induced senescence
      symptoms were more severe in the leaves of the single and double mutants compared
      to wild type leaves. Taken together, our results suggest that ABC1K7 and ABC1K8
      might be involved in the cross-talk between ABA and ROS signaling. 

PMID- 27047532
TI  - Root Zone Cooling and Exogenous Spermidine Root-Pretreatment Promoting Lactuca
      sativa L. Growth and Photosynthesis in the High-temperature Season.
AB  - Root zone high-temperature stress is a major factor limiting hydroponic plant
      growth during the high-temperature season. The effects of root zone cooling (RZC;
      at 25 degrees C) and exogenous spermidine (Spd) root-pretreatment (SRP, 0.1 mM)
      on growth, leaf photosynthetic traits, and chlorophyll fluorescence
      characteristics of hydroponic Lactuca sativa L. grown in a high-temperature
      season (average temperature > 30 degrees C) were examined. Both treatments
      significantly promoted plant growth and photosynthesis in the high-temperature
      season, but the mechanisms of photosynthesis improvement in the hydroponic grown
      lettuce plants were different between the RZC and SRP treatments. The former
      improved plant photosynthesis by increasing stoma conductance (G s) to enhance
      CO2 supply, thus promoting photosynthetic electron transport activity and
      phosphorylation, which improved the level of the photochemical efficiency of
      photosystem II (PSII), rather than enhancing CO2 assimilation efficiency. The
      latter improved plant photosynthesis by enhancing CO2 assimilation efficiency,
      rather than stomatal regulation. Combination of RZC and SRP significantly
      improved P N of lettuce plants in a high-temperature season by both improvement
      of G s to enhance CO2 supply and enhancement of CO2 assimilation. The enhancement
      of photosynthetic efficiency in both treatments was independent of altering light
      harvesting or excessive energy dissipation. 

PMID- 27047533
TI  - Reactive Nitrogen Species in Mitochondria and Their Implications in Plant Energy
      Status and Hypoxic Stress Tolerance.
AB  - Hypoxic and anoxic conditions result in the energy crisis that leads to cell
      damage. Since mitochondria are the primary organelles for energy production, the
      support of these organelles in a functional state is an important task during
      oxygen deprivation. Plant mitochondria adapted the strategy to survive under
      hypoxia by keeping electron transport operative even without oxygen via the use
      of nitrite as a terminal electrons acceptor. The process of nitrite reduction to
      nitric oxide (NO) in the mitochondrial electron transport chain recycles NADH and
      leads to a limited rate of ATP production. The produced ATP alongside with the
      ATP generated by fermentation supports the processes of transcription and
      translation required for hypoxic survival and recovery of plants. Non-symbiotic
      hemoglobins (called phytoglobins in plants) scavenge NO and thus contribute to
      regeneration of NAD(+) and nitrate required for the operation of anaerobic energy
      metabolism. This overall operation represents an important strategy of
      biochemical adaptation that results in the improvement of energy status and
      thereby in protection of plants in the conditions of hypoxic stress. 

PMID- 27047534
TI  - Living on the Edge: Contrasted Wood-Formation Dynamics in Fagus sylvatica and
      Pinus sylvestris under Mediterranean Conditions.
AB  - Wood formation in European beech (Fagus sylvatica L.) and Scots pine (Pinus
      sylvestris L.) was intra-annually monitored to examine plastic responses of the
      xylem phenology according to altitude in one of the southernmost areas of their
      distribution range, i.e., in the Moncayo Natural Park, Spain. The monitoring was
      done from 2011 to 2013 at 1180 and 1580 m a.s.l., corresponding to the lower and
      upper limits of European beech forest in this region. Microcores containing
      phloem, cambium and xylem were collected biweekly from twenty-four trees from the
      beginning of March to the end of November to assess the different phases of wood
      formation. The samples were prepared for light microscopy to observe the
      following phenological phases: onset and end of cell production, onset and end of
      secondary wall formation in xylem cells and onset of cell maturation. The
      temporal dynamics of wood formation widely differed among years, altitudes and
      tree species. For Fagus sylvatica, the onset of cambial activity varied between
      the first week of May and the third week of June. Cambial activity then slowed
      down and stopped in summer, resulting in a length of growing season of 48-75
      days. In contrast, the growing season for P. sylvestris started earlier and
      cambium remained active in autumn, leading to a period of activity varying from
      139-170 days. The intra-annual wood-formation pattern is site and species
      specific. Comparison with other studies shows a clear latitudinal trend in the
      duration of wood formation, positive for Fagus sylvatica and negative for P.
      sylvestris. 

PMID- 27047535
TI  - Global Intersection of Long Non-Coding RNAs with Processed and Unprocessed
      Pseudogenes in the Human Genome.
AB  - Pseudogenes are abundant in the human genome and had long been thought of purely
      as nonfunctional gene fossils. Recent observations point to a role for
      pseudogenes in regulating genes transcriptionally and post-transcriptionally in
      human cells. To computationally interrogate the network space of integrated
      pseudogene and long non-coding RNA regulation in the human transcriptome, we
      developed and implemented an algorithm to identify all long non-coding RNA
      (lncRNA) transcripts that overlap the genomic spans, and specifically the exons,
      of any human pseudogenes in either sense or antisense orientation. As inputs to
      our algorithm, we imported three public repositories of pseudogenes: GENCODE v17
      (processed and unprocessed, Ensembl 72); Retroposed Pseudogenes V5 (processed
      only), and Yale Pseudo60 (processed and unprocessed, Ensembl 60); two public
      lncRNA catalogs: Broad Institute, GENCODE v17; NCBI annotated piRNAs; and NHGRI
      clinical variants. The data sets were retrieved from the UCSC Genome Database
      using the UCSC Table Browser. We identified 2277 loci containing exon-to-exon
      overlaps between pseudogenes, both processed and unprocessed, and long non-coding
      RNA genes. Of these loci we identified 1167 with Genbank EST and full-length cDNA
      support providing direct evidence of transcription on one or both strands with
      exon-to-exon overlaps. The analysis converged on 313 pseudogene-lncRNA exon-to
      exon overlaps that were bidirectionally supported by both full-length cDNAs and
      ESTs. In the process of identifying transcribed pseudogenes, we generated a
      comprehensive, positionally non-redundant encyclopedia of human pseudogenes,
      drawing upon multiple, and formerly disparate public pseudogene repositories.
      Collectively, these observations suggest that pseudogenes are pervasively
      transcribed on both strands and are common drivers of gene regulation. 

PMID- 27047537
TI  - Using Incomplete Trios to Boost Confidence in Family Based Association Studies.
AB  - Most currently available family based association tests are designed to account
      only for nuclear families with complete genotypes for parents as well as
      offspring. Due to the availability of increasingly less expensive generation of
      whole genome sequencing information, genetic studies are able to collect data for
      more families and from large family cohorts with the goal of improving
      statistical power. However, due to missing genotypes, many families are not
      included in the family based association tests, negating the benefits of large
      scale sequencing data. Here, we present the CIFBAT method to use incomplete
      families in Family Based Association Test (FBAT) to evaluate robustness against
      missing data. CIFBAT uses quantile intervals of the FBAT statistic by randomly
      choosing valid completions of incomplete family genotypes based on Mendelian
      inheritance rules. By considering all valid completions equally likely and
      computing quantile intervals over many randomized iterations, CIFBAT avoids
      assumption of a homogeneous population structure or any particular missingness
      pattern in the data. Using simulated data, we show that the quantile intervals
      computed by CIFBAT are useful in validating robustness of the FBAT statistic
      against missing data and in identifying genomic markers with higher precision. We
      also propose a novel set of candidate genomic markers for uterine related
      abnormalities from analysis of familial whole genome sequences, and provide
      validation for a previously established set of candidate markers for Type 1
      diabetes. We have provided a software package that incorporates TDT, robustTDT,
      FBAT, and CIFBAT. The data format proposed for the software uses half the memory
      space that the standard FBAT format (PED) files use, making it efficient for
      large scale genome wide association studies. 

PMID- 27047536
TI  - Computational Detection of Stage-Specific Transcription Factor Clusters during
      Heart Development.
AB  - Transcription factors (TFs) regulate gene expression in living organisms. In
      higher organisms, TFs often interact in non-random combinations with each other
      to control gene transcription. Understanding the interactions is key to decipher
      mechanisms underlying tissue development. The aim of this study was to analyze co
      occurring transcription factor binding sites (TFBSs) in a time series dataset
      from a new cell-culture model of human heart muscle development in order to
      identify common as well as specific co-occurring TFBS pairs in the promoter
      regions of regulated genes which can be essential to enhance cardiac tissue
      developmental processes. To this end, we separated available RNAseq dataset into
      five temporally defined groups: (i) mesoderm induction stage; (ii) early cardiac
      specification stage; (iii) late cardiac specification stage; (iv) early cardiac
      maturation stage; (v) late cardiac maturation stage, where each of these stages
      is characterized by unique differentially expressed genes (DEGs). To identify
      TFBS pairs for each stage, we applied the MatrixCatch algorithm, which is a
      successful method to deduce experimentally described TFBS pairs in the promoters
      of the DEGs. Although DEGs in each stage are distinct, our results show that the
      TFBS pair networks predicted by MatrixCatch for all stages are quite similar.
      Thus, we extend the results of MatrixCatch utilizing a Markov clustering
      algorithm (MCL) to perform network analysis. Using our extended approach, we are
      able to separate the TFBS pair networks in several clusters to highlight stage
      specific co-occurences between TFBSs. Our approach has revealed clusters that are
      either common (NFAT or HMGIY clusters) or specific (SMAD or AP-1 clusters) for
      the individual stages. Several of these clusters are likely to play an important
      role during the cardiomyogenesis. Further, we have shown that the related TFs of
      TFBSs in the clusters indicate potential synergistic or antagonistic interactions
      to switch between different stages. Additionally, our results suggest that
      cardiomyogenesis follows the hourglass model which was already proven for
      Arabidopsis and some vertebrates. This investigation helps us to get a better
      understanding of how each stage of cardiomyogenesis is affected by different
      combination of TFs. Such knowledge may help to understand basic principles of
      stem cell differentiation into cardiomyocytes. 

PMID- 27047538
TI  - Extinction in Phylogenetics and Biogeography: From Timetrees to Patterns of
      Biotic Assemblage.
AB  - Global climate change and its impact on biodiversity levels have made extinction
      a relevant topic in biological research. Yet, until recently, extinction has
      received less attention in macroevolutionary studies than speciation; the reason
      is the difficulty to infer an event that actually eliminates rather than creates
      new taxa. For example, in biogeography, extinction has often been seen as noise,
      introducing homoplasy in biogeographic relationships, rather than a pattern
      generating process. The molecular revolution and the possibility to integrate
      time into phylogenetic reconstructions have allowed studying extinction under
      different perspectives. Here, we review phylogenetic (temporal) and biogeographic
      (spatial) approaches to the inference of extinction and the challenges this
      process poses for reconstructing evolutionary history. Specifically, we focus on
      the problem of discriminating between alternative high extinction scenarios using
      time trees with only extant taxa, and on the confounding effect introduced by
      asymmetric spatial extinction - different rates of extinction across areas - in
      biogeographic inference. Finally, we identify the most promising avenues of
      research in both fields, which include the integration of additional sources of
      evidence such as the fossil record or environmental information in birth-death
      models and biogeographic reconstructions, the development of new models that tie
      extinction rates to phenotypic or environmental variation, or the implementation
      within a Bayesian framework of parametric non-stationary biogeographic models. 

PMID- 27047539
TI  - Genome-Wide Study of Response to Platinum, Taxane, and Combination Therapy in
      Ovarian Cancer: In vitro Phenotypes, Inherited Variation, and Disease Recurrence.
AB  - BACKGROUND: The standard treatment for epithelial ovarian cancer (EOC) patients
      with advanced disease is carboplatin-paclitaxel combination therapy following
      initial debulking surgery, yet there is wide inter-patient variation in clinical
      response. We sought to identify pharmacogenomic markers related to carboplatin
      paclitaxel therapy. METHODS: The lymphoblastoid cell lines, derived from 74
      invasive EOC patients seen at the Mayo Clinic, were treated with increasing
      concentrations of carboplatin and/or paclitaxel and assessed for in vitro drug
      response using MTT viability and caspase3/7 apoptosis assays. Drug response
      phenotypes IC50 (effective dose at which 50% of cells are viable) and EC50 (dose
      resulting in 50% induction of caspase 3/7 activity) were estimated for each
      patient to paclitaxel and carboplatin (alone and in combination). For each of the
      six drug response phenotypes, a genome-wide association study was conducted.
      RESULTS: Statistical analysis found paclitaxel in vitro drug response phenotypes
      to be moderately associated with time to EOC recurrence (p = 0.008 IC50; p =
      0.058 EC50). Although no pharmacogenomic associations were significant at p < 5 *
      10(-8), seven genomic loci were associated with drug response at p < 10(-6),
      including at 4q21.21 for carboplatin, 4p16.1 and 5q23.2 for paclitaxel, and 3q24,
      10q, 1q44, and 13q21 for combination therapy. Nearby genes of interest include
      FRAS1, MGC32805, SNCAIP, SLC9A9, TIAL1, ZNF731P, and PCDH20. CONCLUSIONS: These
      results suggest the existence of genetic loci associated with response to
      platinum-taxane therapies. Further research is needed to understand the mechanism
      by which these loci may impact EOC clinical response to this commonly used
      regimen.

PMID- 27047541
TI  - Methylchloroisothiazolinone/Methylisothiazolinone and Methylisothiazolinone
      Sensitivity in Hungary.
AB  - Background. Due to allowing of methylisothiazolinone (MI) in cosmetics, cleaning
      products, and paints, an epidemic of MI-hypersensitivity emerged. Patch testing
      Kathon CG(r) (3:1 mixture of methylchloroisothiazolinone and
      methylisothiazolinone, MCI/MI) does not correctly detect MI contact allergy, due
      to the low concentration of MI in the test material. Methods. A retrospective
      survey was performed to estimate the prevalence of MCI/MI hypersensitivity in
      14693 patients tested consecutively between 1993 and 2014. Moreover, currently
      314 patients were prospectively tested with the allergens MCI/MI and with MI
      during one year. Results. MCI/MI hypersensitivity increased retrospectively from
      0.5% to 6.0%. By current prospective testing we detected 25 patients (8%) with
      MCI/MI and/or MI positive reactions. Out of the 25 patients 10 were only MCI/MI
      positive, 9 were only MI positive, and 6 were MCI/MI and MI positive. If MI had
      not been tested separately, MI contact allergy would have missed in 36% of all
      detected cases and in 2.8% of the total 314 patients. Conclusions. The frequency
      of MCI/MI hypersensitivity is increasing also in Hungary. We confirm that, in
      order to detect MI contact allergy, it needs to be tested separately. A further
      increase of MI hypersensitivity might be expected in the future as products
      containing MI are still widely available. 

PMID- 27047542
TI  - Clinicoepidemiological Study of Different Types of Warts.
AB  - Background. Warts are cutaneous and, sometimes, mucosal lesions caused by one of
      the several human papilloma viruses. Aim. Assessment of the
      clinicoepidemiological aspects of warts. Materials and Methods. One hundred
      consecutive patients of warts presenting to the department of our institution
      were assigned two broad locational groups: genital and nongenital warts, the
      latter subdivided into common, plane, palmoplantar, mosaic, and
      digitate/filiform. Results. Ninety had nongenital and 10 had genital warts in our
      study; common (42%), palmoplantar (20%), and plane (18%) were the common types of
      the nongenital warts. All the genital warts were acuminate. In the second decade,
      the commonest age group, encompassed all patients of mosaic, 40% of palmoplantar,
      and 20% of genital warts. Overall male (66%) preponderance xisted. All cases of
      filiform warts were males. Mosaic warts affected females more commonly. Students
      (32%), laborers (28%), and housewives (16%) were the usual occupations. Cosmetic
      concern (92%), pain (16%), and itching (15%) were the common complaints. All
      patients of genital warts sought treatment within 6 months. Conclusions. Common,
      palmoplantar, and plane warts were the common types of nongenital warts. Overall
      prevalence peaked during the second decade but one-third of the cases of plane
      warts occurred during the first. Extremities were the most common sites (66.7%);
      face was the next commonly (23%) involved. 

PMID- 27047543
TI  - The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking
      beta-Catenin/TCF Regulated Transcription.
AB  - All colorectal cancer cell lines except RKO displayed active beta-catenin/TCF
      regulated transcription. This feature of RKO was noted in familial colon cancers;
      hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed
      distinct instability of chromosome structure in RKO. Gene expression microarray
      of RKO versus 7 colon cancer lines (with active Wnt signaling) and 3 normal
      specimens revealed 611 differentially expressed genes. The majority of the tested
      gene loci were susceptible to LOH in primary tumors with various beta-catenin
      localizations as a surrogate marker for beta-catenin activation. The
      immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML,
      and GLIPR1) confirmed that they were differentially expressed in clinical
      specimens. Since epigenetic mechanisms can contribute to expression changes,
      selected target genes were evaluated for promoter methylation in patient
      specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML
      were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1
      displayed subgroup specificity. The overall fraction of hypermethylated genes was
      higher in tumors with membranous beta-catenin. We identified novel genes in
      colorectal carcinogenesis that might be useful in personalized tumor profiling.
      Tumors with inactive Wnt signaling are a heterogeneous group displaying
      interaction of chromosomal instability, Wnt signaling, and epigenetics. 

PMID- 27047544
TI  - Efficacy and Toxicity Assessment of Different Antibody Based Antiangiogenic Drugs
      by Computational Docking Method.
AB  - Bevacizumab and trastuzumab are two antibody based antiangiogenic drugs that are
      in clinical practice for the treatment of different cancers. Presently
      applications of these drugs are based on the empirical choice of clinical experts
      that follow towards population based clinical trials and, hence, their molecular
      efficacies in terms of quantitative estimates are not being explored. Moreover,
      different clinical trials with these drugs showed different toxicity symptoms in
      patients. Here, using molecular docking study, we made an attempt to reveal the
      molecular rationale regarding their efficacy and off-target toxicity. Though our
      study reinforces their antiangiogenic potentiality and, among the two,
      trastuzumab has much higher efficacy; however, this study also reveals that
      compared to bevacizumab, trastuzumab has higher toxicity effect, specially on the
      cardiovascular system. This study also reveals the molecular rationale of ocular
      dysfunction by antiangiogenic drugs. The molecular rationale of toxicity as
      revealed in this study may help in the judicious choice as well as therapeutic
      scheduling of these drugs in different cancers. 

PMID- 27047540
TI  - Mouse Genetic Models of Human Brain Disorders.
AB  - Over the past three decades, genetic manipulations in mice have been used in
      neuroscience as a major approach to investigate the in vivo function of genes and
      their alterations. In particular, gene targeting techniques using embryonic stem
      cells have revolutionized the field of mammalian genetics and have been at the
      forefront in the generation of numerous mouse models of human brain disorders. In
      this review, we will first examine childhood developmental disorders such as
      autism, intellectual disability, Fragile X syndrome, and Williams-Beuren
      syndrome. We will then explore psychiatric disorders such as schizophrenia and
      lastly, neurodegenerative disorders including Alzheimer's disease and Parkinson's
      disease. We will outline the creation of these mouse models that range from
      single gene deletions, subtle point mutations to multi-gene manipulations, and
      discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of
      the models outlined in this review will enhance our understanding of the in vivo
      role and underlying mechanisms of disease-related genes in both normal brain
      function and brain disorders, and provide potential therapeutic targets and
      strategies to prevent and treat these diseases. 

PMID- 27047545
TI  - NADPH Oxidase Inhibitor Apocynin Attenuates PCB153-Induced Thyroid Injury in
      Rats.
AB  - PCBs, widespread endocrine disruptors, cause the disturbance of thyroid hormone
      (TH) homeostasis in humans and animals. However, the exact mechanism of thyroid
      dysfunction caused by PCBs is still unknown. In order to clarify the hypotheses
      that NADPH oxidase (NOX) and subsequent NF-kappaB pathway may play roles in
      thyroid dysfunction, sixty Sprague-Dawley rats were randomly divided into four
      groups: control group, PCB153 treated (PCB) group, received apocynin with PCB153
      treatment (APO + PCB) group, and drug control (APO) group. Serum thyroid hormone
      levels were evaluated. The morphological change of thyroid tissue was analyzed
      under the light and transmission electron microscopy. NOX2, 8-OHdG, and NF-kappaB
      expression in the thyroid tissue was evaluated by immune-histochemical staining.
      Oxidative stress and inflammatory cytokines were detected. The following results
      were reduced after apocynin treatment: (1) serum thyroid hormone, (2) thyroid
      pathological injuries, (3) thyroid MDA, (4) thyroid ultrastructural change, (5)
      serum inflammatory cytokines, and (6) thyroid expression of NOX2, 8-OHdG, and NF
      kappaB. These results suggested that NOX inhibition attenuates thyroid
      dysfunction induced by PCB in rats, presumably because of its role in preventing
      ROS generation and inhibiting the activation of NF-kappaB pathway. Our findings
      may provide new therapeutic targets for PCBs induced thyroid dysfunction. 

PMID- 27047546
TI  - Epstein-Barr Virus and Its Association with Oral Hairy Leukoplakia: A Short
      Review.
AB  - In immunocompromised subjects, Epstein-Barr virus (EBV) infection of terminally
      differentiated oral keratinocytes may result in subclinical productive infection
      of the virus in the stratum spinosum and in the stratum granulosum with shedding
      of infectious virions into the oral fluid in the desquamating cells. In a
      minority of cases this productive infection with dysregulation of the cell cycle
      of terminally differentiated epithelial cells may manifest as oral hairy
      leukoplakia. This is a white, hyperkeratotic, benign lesion of low morbidity,
      affecting primarily the lateral border of the tongue. Factors that determine
      whether productive EBV replication within the oral epithelium will cause oral
      hairy leukoplakia include the fitness of local immune responses, the profile of
      EBV gene expression, and local environmental factors. 

PMID- 27047548
TI  - The Impact of Leprosy on Marital Relationships and Sexual Health among Married
      Women in Eastern Nepal.
AB  - Background. Leprosy is one of the most stigmatized diseases known today. The
      stigma surrounding leprosy can be a major burden and affects many dimensions of a
      person's life, including intimate relationships. We aimed to investigate the
      experiences of women affected by leprosy regarding marital life and sexuality,
      comparing these to the experiences of women with other physical disabilities and
      to those of able-bodied women in South-East Nepal. Methods. This study used a
      qualitative approach and a cross-sectional, nonrandom survey design. Thirty women
      underwent in-depth interviews about their marital and sexual relationship by
      means of a semi-structured interview guide. These thirty women included ten women
      affected by leprosy, ten women with other physical disabilities, and ten able
      bodied women living in South-East Nepal. Results. We found that many women faced
      violence and abuse in their marriages. However, women affected by leprosy
      appeared to face more problems with regard to their marital and sexual
      relationships than women with physical disabilities and able-bodied women. Some
      of these related to the fear of leprosy. Conclusions. Further research is
      recommended to investigate the extent of this problem and ways to ameliorate the
      situation of the affected women. Education and counselling at diagnosis may help
      prevent many of the problems reported. 

PMID- 27047549
TI  - A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary
      biliary cirrhosis in Chinese Han.
AB  - BACKGROUND: Several genome-wide association studies of primary biliary cirrhosis
      (PBC) in European and Japanese origins have shown significant association of
      dozens of genetic loci contributive to the susceptibility of PBC. Most of the
      loci were related to immune response pathway. In this study, we tested whether
      the lipid metabolic gene HELZ2 was associated with the pathogenesis of PBC.
      METHODS: In 586 PBC cases (358 in case 1 group and 201 in case 2 group) and 726
      healthy controls of Chinese Han, six nonsynonymous SNPs were genotyped by
      MassArray iPLEX. The same control were used for the two groups of PBC cases.
      Allele frequencies were calculated by chi(2) test based on 2 * 2 contingency
      tables. All data were analyzed using the PLINK tool set. The odds ratio (OR) and
      95 % confidence interval (95 % CI) were calculated, and p values (corrected for
      multiple testing by Bonferroni adjustment) less than 0.05 were considered
      statistically significant. RESULTS: The A allele of rs79267778 was significantly
      associated with PBC (ORcombined = 4.204 [1.670-10.582], p combined  = 1.87E-04).
      It changed the amino acid at position 1904 (NM_001037335) from Threonine (ACG) to
      Methionine (ATG). This site was highly conserved in mammals and predicted to be
      POSSIBLY DAMAGING with a score of 0.469 by PolyPhen-2. It's further predicted
      that T1904 M could INCREASE the protein stability with a confidence at 25.18 %
      under the condition of pH 7.0 and 37  degrees C. CONCLUSION: The result was the
      first time to show evidence of the lipid metabolic gene HELZ2 related to
      autoimmune disease, at least in PBC of Chinese Han.

PMID- 27047550
TI  - Prescribing Antidepressants: Writing a Prescription is the Easiest Part.

PMID- 27047547
TI  - Regenerative Therapy of Type 1 Diabetes Mellitus: From Pancreatic Islet
      Transplantation to Mesenchymal Stem Cells.
AB  - Type 1 diabetes is an autoimmune disease resulting in the permanent destruction
      of pancreatic islets. Islet transplantation to portal vein provides an approach
      to compensate for loss of insulin producing cells. Clinical trials demonstrated
      that even partial islet graft function reduces severe hypoglycemic events in
      patients. However, therapeutic impact is restrained due to shortage of pancreas
      organ donors and instant inflammation occurring in the hepatic environment of the
      graft. We summarize on what is known about regenerative therapy in type 1
      diabetes focusing on pancreatic islet transplantation and new avenues of cell
      substitution. Metabolic pathways and energy production of transplanted cells are
      required to be balanced and protection from inflammation in their intravascular
      bed is desired. Mesenchymal stem cells (MSCs) have anti-inflammatory features,
      and so they are interesting as a therapy for type 1 diabetes. Recently, they were
      reported to reduce hyperglycemia in diabetic rodents, and they were even
      discussed as being turned into endodermal or pancreatic progenitor cells. MSCs
      are recognized to meet the demand of an individual therapy not raising the
      concerns of embryonic or induced pluripotent stem cells for therapy. 

PMID- 27047551
TI  - Update on the Use of SSRIs and SNRIs with Children and Adolescents in Clinical
      Practice.

PMID- 27047552
TI  - A Pilot Study of Citalopram Treatment in Preventing Relapse of Depressive Episode
      after Acute Treatment.
AB  - PURPOSE: To examine the benefit of continuation treatment with citalopram in
      adolescents 13 to 18 years of age with major depression using a multi-site
      randomized placebo controlled discontinuation design. METHODS: Subjects with
      depression who responded to open label treatment with citalopram in 12-week acute
      phase were randomized to continued treatment with citalopram or placebo for 24
      weeks. RESULTS: Twenty five subjects were randomized to either continued
      treatment with citalopram (n = 12) versus placebo (n = 13). Seventy-five percent
      of subjects on citalopram (75%) remained well as compared to placebo (62%). Time
      to relapse was compared between groups using the log rank test and was not found
      to be significantly different (chi(2)(1) = 0.35, P = 0.55). A Cox proportional
      hazards model including drug assignment (hazard ratio (HR = 0.51, 95% CI 0.11 to
      2.36, P = 0.39), gender (HR = 0.58, 95% CI 0.14 to 2.37, P = 0.44), or HAM-score
      at entry to continuation phase (HR = 1.33, 95% CI 0.90 to 1.95, P = 0.95) was not
      significant. CONCLUSION: Although we did not find statistically significant
      differences between citalopram and placebo, the findings suggest a possible
      benefit of continued treatment with citalopram over placebo. A larger clinical
      trial with adequate power is required to confirm or disconfirm these findings.

PMID- 27047553
TI  - Resilience and Stress in Children and Adolescents with Specific Learning
      Disability.
AB  - OBJECTIVE: Presence of Specific Learning Disorder (SLD) can be extremely
      frustrating for a child. The present study aimed to assess the levels of
      resilience, depression, anxiety and stress among children and adolescents having
      SLD and to compare with those having Borderline Intellectual Functioning (BIF).
      It also aimed to evaluate the parental awareness about their child's learning
      disorder. METHODOLOGY: Eighty two children and adolescents, diagnosed as having
      SLD (N=41) and BIF (N=41) were selected for the present study. The participants
      completed Resilience Scale-14 and Depression, Anxiety and Stress Scales and
      parents completed the Parent Interview Profroma. RESULT: Low level of Resilience
      was found in 75% of the children and adolescents with SLD. Severe Stress (16.6%),
      severe Depression (14.2%) and severe Anxiety (23.8%) were seen in this sample.
      The level of Resilience was lower among participants with SLD as compared to
      those with BIF. Ninety percent of parents were aware that their child had SLD,
      however, only 39% gave individual attention for assisting them in their studies.
      CONCLUSION: The present study emphasizes the importance of individualized
      interventions dealing not only with remedial training, but also for incorporating
      components including parental awareness of the emotional consequences of SLD as
      well as individual interventions for children, focusing on strengthening their
      coping and Resilience.

PMID- 27047554
TI  - Canadian Rural/Remote Primary Care Physicians Perspectives on Child/Adolescent
      Mental Health Care Service Delivery.
AB  - INTRODUCTION: Primary Care Physicians (PCP) play a key role in the recognition
      and management of child/adolescent mental health struggles. In rural and under
      serviced areas of Canada, there is a gap between child/adolescent mental health
      needs and service provision. METHODS: From a Canadian national needs assessment
      survey, PCPs' narrative comments were examined using quantitative and qualitative
      approaches. Using the phenomenological method, individual comments were drawn
      upon to illustrate the themes that emerged. These themes were further analyzed
      using chi-square to identify significant differences in the frequency in which
      they were reported. RESULTS: Out of 909 PCPs completing the survey, 39.38% (n =
      358) wrote comments. Major themes that emerged were: 1) psychiatrist access,
      including issues such as long waiting lists, no child/adolescent psychiatrists
      available, no direct access to child/adolescent psychiatrists; 2) poor
      communication/continuity, need for more systemized/transparent referral
      processes, and need to rely on adult psychiatrists; and, 3) referral of patients
      to other mental health professionals such as paediatricians, psychologists, and
      social workers. CONCLUSIONS: Concerns that emerged across sites primarily
      revolved around lack of access to care and systems issues that interfere with
      effective service delivery. These concerns suggest potential opportunities for
      future improvement of service delivery. IMPLICATIONS: Although the survey only
      had one comment box located at the end, PCPs wrote their comments throughout the
      survey. Further research focusing on PCPs' expressed written concerns may give
      further insight into child/adolescent mental health care service delivery
      systems. A comparative study targeting urban versus rural regions in Canada may
      provide further valuable insights.

PMID- 27047555
TI  - The CASA Trauma and Attachment Group (TAG) Program for Children who have
      Attachment Issues Following Early Developmental Trauma.
AB  - OBJECTIVE: There is relatively little research about effective therapeutic
      approaches for children in middle childhood who have attachment related diagnoses
      as a result of experiencing significant, early developmental trauma. This study
      describes findings from an intensive, dyad-based intervention, aimed at
      stabilizing attachment relationships with primary caregivers, increasing
      caregiver reflective function skills, and reducing children's trauma-related
      behavioural sequelae. METHOD: We analyzed retrospective data from 51
      caregiver/child dyads who participated in the Trauma and Attachment Group (TAG)
      Program from September 2011-December 2014. This data included pre- and post
      intervention scores retrieved from the Parenting Relationship Questionnaire
      (PRQ), the Parent Report of Post-Traumatic Stress Symptoms (PROPS), and the
      Parental Reflective Functioning Questionnaire (PRFQ-1). RESULTS: The preliminary
      findings show statistically significant improvements in attachment,
      communication, discipline practices, involvement, and relational frustration.
      Additionally there were statistically significant improvements in parental
      reflective functioning, and a trend towards a reduction in symptoms typical of
      post-traumatic stress disorder. CONCLUSION: Poor quality or inconsistent
      interactions with early caregivers can lead to life-long impairments in physical
      and mental health. This intensive program shows potential as a way to improve
      longer-term outcomes for children exposed to early developmental trauma. Longer
      term research is required to further substantiate outcomes, appraise cost
      analysis, as well as to consider evaluation with appropriate comparison groups.

PMID- 27047556
TI  - Genetic Polymorphism in the Promoter Region of Serotonin Transporter:
      Implications for Ethanol Abuse in Children and Adolescents.
AB  - OBJECTIVES: To provide a review of published literature regarding genetic
      polymorphism of serotonin transporter gene, named as 5-HTTLPR, and its potential
      role as a susceptibility marker for ethanol abuse in childhood and adolescence.
      METHODS: A literature review of several databases was conducted with the
      following keywords: 5-HTTLPR, children or adolescents or teenagers,
      susceptibility, alcohol or ethanol, abuse or misuse. RESULTS: Alcohol interacts
      with serotonergic synaptic transmission in several ways, and the reduced
      availability of serotonin transporters might foster brain dysfunction, driving to
      alcohol abuse. The initial use of ethanol in children and adolescents is
      determined primarily by environmental influences, whereas the establishment of
      drinking patterns is strongly controlled by genetic factors. Functional
      polymorphic variants in the promoter region of the 5-HTTLPR gene have age
      dependent effects in alcohol abuse. This polymorphism, mapped to the 5' region of
      the SLC6A4, is a variable number of tandem repeats (VNTR) and involves a direct
      repeat of 20-23 base pairs GC-rich sequences, comprising a short (S) allele,
      consisting of 14 repeats, and a long (L) allele, with 16 repeats. Additional
      variants have been described, although their influences on childhood and
      adolescence ethanol use are not clear. CONCLUSION: The influence of the 5-HTTLPR
      allelic variants in children and adolescent misuse of alcohol might be considered
      for clinical management, preventing long-term behavior problem. Identifying
      genetic markers associated to the potential alcohol misuse or abuse could be
      useful in guiding management and formulating effective coping strategies.

PMID- 27047559
TI  - [Not Available].

PMID- 27047557
TI  - Epilepsy, Attention-Deficit/Hyperactivity Disorder and Methylphenidate: Critical
      Examination of Guiding Evidence.
AB  - OBJECTIVE: Attention-Deficit/Hyperactivity Disorder (ADHD) and epilepsy are
      commonly comorbid; yet in the psychiatric literature, there is a remarkable
      paucity of guiding evidence regarding the safety and efficacy of treatment using
      methylphenidate (MPH) in this population. The objective of this review is to
      critically appraise evidence regarding the treatment of ADHD in the context of
      seizure disorders in order to better inform management considerations and
      practices. METHOD: A comprehensive search of the Central, Embase, Medline, and
      Web of Science databases identified 349 references. After a thorough review, only
      nine relevant references contributing new information and providing reliable and
      interpretable data were identified; seven were prospective studies (two double
      blind placebo controlled trials, five open-label trials) and two were
      retrospective reviews. Prospective studies were then reviewed in detail,
      critically appraised, and interpreted. RESULTS: All studies reported no increase
      in seizure rates in a majority of participants after exposure to MPH. MPH was
      effective in treating ADHD symptoms. However, the following major limitations to
      the studies impede drawing confident conclusions: small sample sizes, lack of
      uniformity regarding seizure type and severity, seizure-free period pre-stimulant
      treatment, and low baseline seizure rates. CONCLUSIONS: Given the academic,
      social, emotional, and functional impact of untreated ADHD, a watchful approach
      to the use of MPH in children with stable epilepsy who are impaired by ADHD
      symptoms is justified.

PMID- 27047560
TI  - A Comparative Study of Whole Body Vibration Training and Pelvic Floor Muscle
      Training on Women's Stress Urinary Incontinence: Three- Month Follow- Up.
AB  - OBJECTIVE: To determine whether Whole Body Vibration Training (WBVT) is effective
      at improving pelvic floor muscles strength in women with Stress Urinary
      Incontinence (SUI). MATERIALS AND METHODS: The study was designed as a randomized
      clinical trial. 43 women with SUI were randomly assigned in two groups; WBVT and
      Pelvic Floor Muscle Training (PFMT) and received interventions for four weeks.
      Pelvic floor muscle (PFM) strength, quality of life and incontinence intensity
      were evaluated. All measurements were conducted pre and post intervention and
      also after 3 months in all participants. The ANOVA and the independent sample t
      test were applied respectively to determine the differences in each group and
      between the groups. RESULTS: This study showed the WBVT protocol in this study
      was effective in pelvic floor muscles strength similar to PFMT, and also in
      reducing the severity of incontinence and increasing I-QOL questionnaire score.
      We found significant differences in each group pre and post intervention (p =
      0.0001); but no significant difference in comparison of two groups' outcomes.
      Also after three-month follow up, there was no significant difference between
      groups. CONCLUSION: The findings of this study showed the beneficial effects of
      WBVT in improving pelvic floor muscles strength and quality of life in patients
      with urinary incontinence in four-week treatment period and after three months
      follow up.

PMID- 27047561
TI  - SPO11-C631T Gene Polymorphism: Association With Male Infertility and an in Silico
      Analysis.
AB  - OBJECTIVE: To investigate the association of C631T single nucleotide
      polymorphisms in SPO11 gene with male infertilityfollowed by an in silico
      approach. SPO11 is a gene involved in meiosis and spermatogenesis process, which
      in humans, this gene is located on chromosome 20 (20q13.2-13.3) with 13 exons.
      MATERIALS AND METHODS: In a case-control study, 200 blood samples were collected
      from the IVF center (Kashan, Iran) including; 100 infertile and 100 healthy
      control men. SPO11-C631T were genotyped using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method.The effects of C631T
      transition on the structure of mRNA and protein of SPO11 was evaluated by
      bioinformatics tools. RESULTS: Our data revealed that all subjects were wild-type
      homozygous inC631T positionsand just a sample from fertile group was
      heterozygousin C631T (OR: 0.3300, 95% CI: 0.0133 to 8.1992, p = 0.4988).Our in
      silico-analysis revealed that C631T transition could make fundamental changes in
      the structure of the mRNA (Score: 0.1983) and protein (PROVEAN Score: -3.371;
      Reliability Index: 4; Expected Accuracy: 82%) of SPO11. Also, C631T substitution
      could change the aggregation prone regions of the SPO11 protein (dTANGO =
      209.99). CONCLUSION: So even though the SPO11-C631T don't increase the risk of
      male infertility, it could be deleterious for themRNA and protein.

PMID- 27047562
TI  - Validity and Reliability of Persian Version of HIV/AIDS Related Stigma Scale for
      People Living With HIV/AIDS in Iran.
AB  - OBJECTIVE: To assess the perceived HIV/AIDS related stigma a comprehensive and
      well developed stigma instrument is necessary. This study aimed to assess
      validity and reliability of the Persian version of HIV/AIDS related stigma scale
      which was developed by Kang et al for people living with HIV/AIDS in Iran.
      MATERIALS AND METHODS: Thescale was forward translatedby two bilingual academic
      members then both translations were discussed by expert team. Back-translation
      was done by two other bilingual translators then we carried out discussion with
      both of them. To evaluate understandability the scale was administered to 10
      Persons Living with HIV/AIDS (PLWHA). Final Persian version was administered to
      80 PLWHA in Qom, Iran in 2014. Test-retest reliability was assessed in a sample
      of 20 PLWHA after a week by intra-class correlation coefficient (ICC). RESULTS:
      Cronbach's alpha coefficient for overall scale was 0.85. Also Cronbach's alpha
      coefficients for the five subscales were as follows: social rejection (9 items,
      alpha = 0.84), negative self-worth (4 items, alpha = 0.70), perceived
      interpersonal insecurity (2 items, alpha = 0.57), financial insecurity (3 items,
      alpha = 0.70), discretionary disclosure (2 items, alpha = 0.83). Test-retest
      reliability was also approved with ICC = 0.78. Correlation between items and
      their hypothesized subscale is greater than 0.5. Correlation between an item and
      its own subscale was significantly higher than its correlation with other
      subscales. CONCLUSION: This study demonstrate that the Persian version of
      HIV/AIDS related stigma scale is valid and reliable to assess HIV/AIDS related
      stigma perceived by people living whit HIV/AIDS in Iran.

PMID- 27047563
TI  - Effects of Metformin Treatment on Homocysteine Levels and Metabolic Parameters of
      Women With Polycystic Ovary Syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine
      disorders in women. Metformin is a biguanide commonly used to improve PCOS
      symptoms. Effect of metformin on the levels of serum homocysteine (Hcy) in PCOS
      women is unclear. The aim of this study is evaluating the effect of metformin
      administration on serum Hcy levels and metabolic parameters of PCOS patients.
      MATERIALS AND METHODS: Thirty three patients with PCOS were enrolled in this
      study who were selected randomly. All patients received metformin from the fifth
      day of menstrual cycle at a dose of 850 mg (one tablet daily) for 3 months. Body
      mass index, Triglycerides, total cholesterol, high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood
      sugar and homocysteine levels were recorded at entry into the study and after 3
      months treatment. RESULTS: BMI, plasma Homocysteine concentrations and fasting
      blood sugar levels were significantly (p < 0.05) decreased after the treatment
      period. No significant changes were observed in the lipid profiles of patients.
      There was a weak negative correlation between homocysteine and LDL cholesterol
      serum levels (p = 0.04, r = -0.27). CONCLUSION: Treatment with metformin in PCOS
      women may lead to beneficial effects in terms of BMI, plasma homocysteine
      concentrations and fasting blood sugar with no remarkable effect on lipid
      profile.

PMID- 27047564
TI  - Utility of Pelvic MRI and Tumor Markers HE4 and CA125 to Predict Depth of
      Myometrial Invasion and Cervical Involvement in Endometrial Cancer.
AB  - OBJECTIVE: The purpose of this pilot study was to determine whether the MRI and
      biomarkers human epididymis protein 4 (HE4) and CA125 correlate with depth of
      myometrial invasion, histologic grade, cervical involvement and nodal metastases
      in patients with endometrioid adenocarcinoma of the uterus. MATERIALS AND
      METHODS: This was a prospective, observational study in women with biopsy-proven
      endometrial adenocarcinoma of the uterus. Preoperative pelvic MRI was performed
      and concentration of HE4 and CA125 were assessed before surgery. All surgical
      specimens were reviewed by a single expert pathologist. The results were compared
      with the final histopathology report of surgical staging. RESULTS: Included were
      a total of 68 women with endometrioid adenocarcinoma of the uterus, most (76%)
      with stage I disease. Levels of serum HE4 greater than 140PM and CA125 greater
      than 35 ku/L were observed in 12 (17%) and 26 (38.2%) of patients respectively
      whose greater proportion were cases with deep myometrial invasion and high grade
      tumor. In the evaluation of deep tumoral invasion (> 50%) of the myometrium
      sensitivity, specificity, and diagnostic accuracy of MRI were 68.9%, 94.8% and
      83.8% respectively. For lymph node involvement these values were 50%, 95.1% and
      91.1% respectively and for cervical stromal involvement were 64.3%, 98.1% and
      91.1% respectively. CONCLUSION: Higher stage, deep myometrial invasion, and lymph
      node or cervical stromal involvement increase diagnostic accuracy of MRI. Higher
      levels of HE4 and CA125 were observed in patients with deep myometrial invasion
      and higher grade of tumor.

PMID- 27047565
TI  - Psychometric Properties of the Iranian Version of Modified RHAQWRA Questionnaire.
AB  - OBJECTIVE: This study aimed to examin the psychometric characteristics of the
      Persian version of Reproductive Health Assessment Questionnaire for Women of
      Reproductive Age (RHAQWRA). MATERIALS AND METHODS: This study was a cross
      sectional study. We selected 150 women aged 18- 45 years based on convenience
      sampling method who lived in the Quake-hit areas in eastern part of Iran in 2013.
      Some previously recognized and established instructions were undertaken in
      translating and adapting the RHAQWRA questionnaire culturally. We sought help and
      feedback from teenagers and experts in the fields of midwifery, sociology, and
      epidemiology to establish the face and content validity of the questionnaire. To
      examine the test-retest reliability indices of all the items, we used Kappa and
      McNemar tests. RESULTS: The Content Validity Index (CVI) and Content Validity
      Ratio (CVR) scores for RHAQWRA were above 0.70. RESULTS from Kappa and McNemar
      tests indicated a high degree of test-retest reliability. In order to evaluate
      the construct validity, known- group comparison (women with and without unwanted
      pregnancy) was used. The internal consistency reliability indexes for the
      subscales obtained through Cronbach's alpha were between 0.68 and 0.87.
      CONCLUSION: The findings suggest that the Iranian version of RHAQWRA is a valid
      and reliable questionnaire which can be used for measuring reproductive health
      needs during disasters.

PMID- 27047566
TI  - Comparison Between Intraperitoneal and Intravenous Lidocaine for Postoperative
      Analgesia After Elective Abdominal Hysterectomy, a Double-Blind Placebo
      Controlled Study.
AB  - OBJECTIVE: To compare the efficacy of intravenous and intraperitoneal injection
      of lidocaine and normal saline in relieving postoperative pain after elective
      abdominal hysterectomy. MATERIALS AND METHODS: For this double-blind randomized
      controlled study 109 patients undergoing elective abdominal hysterectomy were
      randomly allocated to three groups :1) IV group (intravenous injection group)
      received intravenous lidocaine %2 bolus 1.5mg/kg 30 min before incision and then
      a continuous lidocaine infusion of 2mg/kg and before the wound closure an
      intraperitoneal injection of N/S , 2) IP group (intraperitoneal group) received
      intravenous N/S and intraperitoneal lidocaine 3mg/kg , 3) P group (placebo, N/S)
      received both intravenous and intraperitoneal N/S. The pain scores (VAS) at rest,
      total morphine consumption , the time to first need for rescue analgesic
      ,incidence of lidocaine related adverse effects and nausea and vomiting were
      recorded at 0,2,4,8,12 and 24 hrs postoperatively. RESULTS: The VAS scores were
      significantly lower in IP and IV groups compared with placebo (p = 0.001). Total
      consumption of morphine (p = 0.001) and time to firs request of recue analgesic
      (p = 0.001) were lower too in IP and IV groups.Incidence of vomiting was
      comparable between groups (p < 0.05) but nausea was higher in control group (p >
      0.05).There were not notable lidocaine-related adverse effects. IP and IV groups
      were not statistically different for all investigated variables. CONCLUSION: This
      study showed lidocaine administration both intravenously and intraperitoneally
      are effective in reducing the postoperative pain and also have opioid sparing
      effect and can be safely used in elective abdominal hysterectomy without any
      major adverse effects.

PMID- 27047567
TI  - Benign Vulvar Adnexal Tumours - A 5 year Study in a Tertiary Care Hospital.
AB  - Despite of the fact that the vulva contains a high density of apocrine and
      anogenital mammary glands in addition to eccrine glands and folliculosebaceous
      units, the benign vulvar adnexal tumours are rare. Though the varied clinical
      presentation and diverse histopathological spectrum of vulvar neoplasms has
      amazed the pathologists, only few studies have been reported in literature. The
      present five year study consists of only five cases of benign vulvar neoplasms
      depicting their rarity. Hidradenoma papilliferum and syringoma were the most
      common entities followed by Chondroid syringoma. The aim of our study is to
      explore and highlight the histopathological diversity of benign vulvar adnexal
      tumours reflecting the relative frequency of these structures. 

PMID- 27047568
TI  - Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy.
AB  - Objective. Herbal medicine has been widely used to treat drug resistant epilepsy.
      Shihogyejitang (SGT) has been commonly used to treat epilepsy. We investigated
      the effect and safety of SGT in children with drug resistant epilepsy. Design. We
      reviewed medical records of 54 patients with epilepsy, who failed to respond to
      at least two antiepileptic drugs and have been treated with SGT between April
      2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital,
      Korea. Effect was measured by the response rate, seizure-free rate, and retention
      rate at six months. We also checked adverse events, change in antiepileptic drugs
      use, and the variables related to the outcome. Results. Intent-to-treat analysis
      showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1%
      including seizure-free, respectively, and 53.7% remained on SGT. Two adverse
      events were reported, mild skin rash and fever. Focal seizure type presented
      significantly more positive responses when compared with other seizure types at
      six months (p = 0.0284, Fisher's exact test). Conclusion. SGT is an effective
      treatment with excellent tolerability for drug resistant epilepsy patients. Our
      data provide evidence that SGT may be used as alternative treatment option when
      antiepileptic drug does not work in epilepsy children. 

PMID- 27047569
TI  - Glucotoxicity Induced Oxidative Stress and Inflammation In Vivo and In Vitro in
      Psammomys obesus: Involvement of Aqueous Extract of Brassica rapa rapifera.
AB  - Context. Brassica rapa is considered as natural source of antioxidants and is
      used to treat diabetes. Objective. Our study carried the impact of glucotoxicity
      induced in vivo and in vitro in vascular smooth muscle cells (VSMCs) in Psammomys
      and the therapeutic effect of Brassica rapa (AEBr). Materials and Methods. We
      administered a hyperglucidic diet (30% sucrose) for 9 months and a treatment for
      20 days with AEBr at 100 mg/kg. VSMCs were submitted to D-Glucose (0.6%) for 48
      hours and treated with AEBr (2100 MUg/mL) for 24 hours. We measured, in blood
      metabolic parameters, the redox statues and inflammatory markers in adipose
      tissue. Histological study was effectuated in liver. In VSMCs, we measured
      markers of glucotoxicity (IRS1p Serine, AKT) inflammation (NO, MCP1, TNFalpha,
      and NF-kappaB) and oxidative stress (oxidants and antioxydants markers). Cell
      viability and apoptosis were estimated by the morphological study. Results. AEBr
      corrects the metabolic parameters and inflammatory and oxidative markers in blood
      and homogenate tissue and reduces lipid droplets in liver. It induces, in VSMCs,
      a significant decrease of IRS1p serine, cyt c, NO, MCP1, TNFalpha, NF-kappaB,
      protein, and lipid oxidation and increases cell viability, AKT, ERK1/2, catalase,
      and SOD activity. Conclusion. Brassica enhanced the antidiabetic, anti
      inflammatory, and antioxidant defense leading to the protection of cardiovascular
      diseases. 

PMID- 27047570
TI  - Genotyping of Salmonella Typhi using 8-loci multi locus VNTR analysis.
AB  - BACKGROUND: Typhoid fever has caused severe epidemics in many Asian and African
      countries. The early detection of outbreaks and their sources may promote the
      prevention and control of typhoid fever, for which effective and timely molecular
      subtyping techniques are required. Pulsed field gel electrophoresis (PFGE) is
      routinely used as the molecular typing technique for foodborne and waterborne
      pathogens. However, maneuverable techniques remain necessary to expedite the
      experimental procedure and obtain more effective subtyping. The multilocus loci
      of a variable number of tandem repeats (VNTR) analysis (MLVA) is a polymerase
      chain reaction (PCR)-based subtyping method. METHODS: MLVA method and PFGE based
      on Xba I enzyme were applied to the 103 Salmonella Typhi (S. Typhi) isolated from
      different years and regions. Dendrograms were constructed and analyzed to help
      understand the data. The Simpson's index of diversity (D value) was calculated to
      estimate the discriminatory power of MLVA and PFGE. In addition, a set of
      endogenous 3 bp DNA ladder markers were established to accurately determine the
      repeat copy number of the VNTR with only a 3 bp repetitive unit, using
      microfluidics chip-based electrophoresis to generate comparable VNTR data in the
      public health laboratory network. RESULTS: The established 8-loci MLVA for S.
      Typhi subtyping had higher discriminatory power than PFGE. In some cases, PFGE
      could not distinguish the strains isolated over long intervals and with different
      epidemic provinces. By contrast, 8-loci MLVA distinctly distinguished these
      strains, and the strains with the same MLVA patterns were from the same or
      contiguous years and the same province, showing its significance in
      epidemiological discrimination. The established set of endogenous 3 bp DNA ladder
      markers improved the accuracy and reproducibility of VNTR analysis using
      microfluidics chip-based electrophoresis to 100 %. CONCLUSIONS: Eight VNTRs can
      be used for the MLVA analysis of the 103 S. Typhi isolates. MLVA based on the 8
      loci had higher discriminatory power than PFGE for S. Typhi subtyping. The 8-loci
      MLVA is easier for the analysis and interpretation of relationships between
      strains compared to PFGE.

PMID- 27047571
TI  - Homologous platelet-rich plasma for the treatment of knee osteoarthritis in
      selected elderly patients: an open-label, uncontrolled, pilot study.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and the effect
      of platelet-rich plasma (PRP) intra-articular injections obtained from blood
      donors (homologous PRP) on elderly patients with early or moderate knee
      osteoarthritis (OA) who are not candidates for autologous PRP treatment. METHODS:
      A total of 60 symptomatic patients, aged 65-86 years, affected by hematologic
      disorders and early or moderate knee OA, were treated with 5 ml of homologous PRP
      intra-articular injections every 14 days for a total of three injections.
      Clinical evaluations before the treatment, and after 2 and 6 months were
      performed by International Knee Documentation Committee (IKDC), Knee injury and
      Osteoarthritis Outcome Score (KOOS) and Equal Visual Analogue Scale (EQ VAS)
      scores. Adverse events and patient satisfaction were recorded. RESULTS: No severe
      complications were noted during the treatment and the follow-up period. A
      statistically significant improvement from basal evaluation to the 2-month follow
      up visit was observed, whereas a statistically significant worsening from the 2
      month to the 6-month follow-up visit was showed. The overall worst results were
      observed in patients aged 80 years or over and in those affected by minor bone
      attrition. It was found that 90% of patients were satisfied at the 6-month
      evaluation. CONCLUSIONS: Homologous PRP has an excellent safety profile but
      offers only a short-term clinical improvement in selected elderly patients with
      knee OA who are not candidates for autologous PRP treatment. Increasing age and
      developing degeneration result in a decreased potential for homologous PRP
      injection therapy. Further studies are needed to confirm these findings.

PMID- 27047572
TI  - Disease-modifying antirheumatic drugs improve cardiovascular autonomic neuropathy
      in psoriatic arthritis.
AB  - BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a significant risk
      predictor for sudden cardiac death in autoimmune rheumatic diseases. As yet,
      there is no therapeutic treatment of CAN in psoriatic arthritis (PsA). Even now,
      the impact of the most commonly employed disease-modifying antirheumatic drug
      (DMARD) therapy on CAN in PsA is not known. Hence, we investigated the impact of
      DMARDs on CAN in PsA. METHODS: In this prospective, cross-sectional study, 20
      patients of PsA and 20 age- and sex-matched healthy controls were recruited. CAN
      was diagnosed by applying the five cardiovascular reflex tests according to
      Ewing. Parasympathetic dysfunction was established by performing three tests:
      heart-rate response to deep breathing, standing, and Valsalva tests. Sympathetic
      dysfunction was examined by applying two tests: blood pressure response to
      standing, and handgrip tests. Disease severity was assessed by the 28-joint-count
      disease activity score (DAS-28) and the disease activity score in psoriatic
      arthritis (DAPSA). RESULTS: Cardiovascular reflex tests were impaired
      significantly among the PsA patients compared with well-matched healthy subjects
      (p < 0.05). Parasympathetic dysfunction was more prominent than sympathetic
      dysfunction. After 12 weeks treatment, parasympathetic dysfunction (heart rate
      response to deep breath and standing) significantly (p < 0.05) improved in
      patients with PsA, while there was no significant improvement in sympathetic
      function. CONCLUSION: These study results suggests parasympathetic autonomic
      dysfunction is more prominent than sympathetic dysfunction in PsA. Synthetic
      DMARDs improved parasympathetic dysfunction in PsA.

PMID- 27047573
TI  - A case of missed ocular torticollis.

PMID- 27047574
TI  - Trigger finger: ultrasound-guided injection with an in-plane approach under the
      A1 pulley.

PMID- 27047575
TI  - Retraction Notice: An Injectable Complex of beta-tricalcium Phosphate Granules,
      Hyaluronate, and rhFGF-2 on Repair of Long-bone Fractures with Large Fragments.

PMID- 27047576
TI  - Association Study of Single Nucleotide Polymorphisms Rs4552569/Rs17095830 with
      Ankylosing Spondylitis in A Chinese Population.
AB  - Genetics play a key role in ankylosing spondylitis (AS). A previous genome-wide
      association study (GWAS) showed that rs4552569 (on 5q14.3) and rs17095830 (on
      12q12) were associated with the risk of AS in Han Chinese, which was not
      replicated in other two studies. In the current study, rs4552569 and rs17095830
      were genotyped in 735 Han Chinese AS patients and 1204 healthy controls using
      high resolution melting analysis (HRMA). We compared the distributions of
      genotypes and alleles between AS cases and healthy controls. Rs30187 and
      rs10865331, which were reported to be associated with AS susceptibility in
      various populations, were also genotyped and analyzed as positive controls. The
      results showed that no association between rs4552569/rs17095830 polymorphisms and
      AS susceptibility was found. On the other hand, an association between rs17095830
      and one of AS complication (inflammatory bowel disease) was observed (allelic P
      value=0.0180; odds ratio[OR]=1.739; 95% confidence interval [CI]=1.146-2.639). 

PMID- 27047577
TI  - A summary of a Cochrane review: Midwife-led care for childbearing women.

PMID- 27047578
TI  - Introducing the JMBE Themed Issue on Scientific Citizenship.

PMID- 27047579
TI  - Letter to the Editor.

PMID- 27047580
TI  - The Tragedy of the Unexamined Cat: Why K-12 and University Education Are Still in
      the Dark Ages and How Citizen Science Allows for a Renaissance.
AB  - At the end of the dark ages, anatomy was taught as though everything that could
      be known was known. Scholars learned about what had been discovered rather than
      how to make discoveries. This was true even though the body (and the rest of
      biology) was very poorly understood. The renaissance eventually brought a
      revolution in how scholars (and graduate students) were trained and worked. This
      revolution never occurred in K-12 or university education such that we now teach
      young students in much the way that scholars were taught in the dark ages, we
      teach them what is already known rather than the process of knowing. Citizen
      science offers a way to change K-12 and university education and, in doing so,
      complete the renaissance. Here we offer an example of such an approach and call
      for change in the way students are taught science, change that is more possible
      than it has ever been and is, nonetheless, five hundred years delayed. 

PMID- 27047581
TI  - The Power of Engaging Citizen Scientists for Scientific Progress.
AB  - Citizen science has become a powerful force for scientific inquiry, providing
      researchers with access to a vast array of data points while connecting
      nonscientists to the authentic process of science. This citizen-researcher
      relationship creates an incredible synergy, allowing for the creation, execution,
      and analysis of research projects that would otherwise prove impossible in
      traditional research settings, namely due to the scope of needed human or
      financial resources (or both). However, citizen-science projects are not without
      their challenges. For instance, as projects are scaled up, there is concern
      regarding the rigor and usability of data collected by citizens who are not
      formally trained in research science. While these concerns are legitimate, we
      have seen examples of highly successful citizen-science projects from multiple
      scientific disciplines that have enhanced our collective understanding of
      science, such as how RNA molecules fold or determining the microbial metagenomic
      snapshot of an entire public transportation system. These and other emerging
      citizen-science projects show how improved protocols for reliable, large-scale
      science can realize both an improvement of scientific understanding for the
      general public and novel views of the world around us. 

PMID- 27047582
TI  - Citizen Science Initiatives: Engaging the Public and Demystifying Science.
AB  - The Internet and smart phone technologies have opened up new avenues for
      collaboration among scientists around the world. These technologies have also
      expanded citizen science opportunities and public participation in scientific
      research (PPSR). Here we discuss citizen science, what it is, who does it, and
      the variety of projects and methods used to increase scientific knowledge and
      scientific literacy. We describe a number of different types of citizen-science
      projects. These greatly increase the number of people involved, helping to speed
      the pace of data analysis and allowing science to advance more rapidly. As a
      result of the numerous advantages of citizen-science projects, these
      opportunities are likely to expand in the future and increase the rate of novel
      discoveries. 

PMID- 27047583
TI  - Current Approaches in Implementing Citizen Science in the Classroom.
AB  - Citizen science involves a partnership between inexperienced volunteers and
      trained scientists engaging in research. In addition to its obvious benefit of
      accelerating data collection, citizen science has an unexplored role in the
      classroom, from K-12 schools to higher education. With recent studies showing a
      weakening in scientific competency of American students, incorporating citizen
      science initiatives in the curriculum provides a means to address deficiencies in
      a fragmented educational system. The integration of traditional and innovative
      pedagogical methods to reform our educational system is therefore imperative in
      order to provide practical experiences in scientific inquiry, critical thinking,
      and problem solving for school-age individuals. Citizen science can be used to
      emphasize the recognition and use of systematic approaches to solve problems
      affecting the community. 

PMID- 27047584
TI  - Microbes Should Be Central to Ecological Education and Outreach.
AB  - Our planet is changing rapidly, and responding to the ensuing environmental
      challenges will require an informed citizenry that can understand the inherent
      complexity of ecological systems. However, microorganisms are usually neglected
      in the narratives that we use to understand nature. Here, we advocate for the
      inclusion of microbial ecology across education levels and delineate the often
      neglected benefits of incorporating microbes into ecology curricula. We provide
      examples across education levels, from secondary school (by considering one's
      self as a microbial ecosystem), to higher education (by incorporating our
      knowledge of the global ecological role and medical application of microbes), to
      the general public (by engagement through citizen-science projects). The greater
      inclusion of microbes in ecological education and outreach will not only help us
      appreciate the natural world we are part of, but will ultimately aid in building
      a citizenry better prepared to make informed decisions on health and
      environmental policies. 

PMID- 27047585
TI  - The Engaged Microbiologist: Bringing the Microbiological Sciences to the K-12
      Community.
AB  - Exposing K-12 students to cutting edge science that impacts their daily lives can
      bring classroom lessons to life. Citizen-science projects are an excellent way to
      bring high-level science to the classroom and help satisfy one of the cornerstone
      concepts of the Next Generation Science Standards (NGSS), "engaging in practices
      that scientists and engineers actually use." This can be a daunting task for
      teachers who may lack the background or resources to integrate these projects
      into the classroom. This is where scientific societies such as the American
      Society for Microbiology (ASM) can play a critical role. ASM encourages its
      members to engage with the K-12 community by providing networking opportunities
      and resources for ASM members and K-12 teachers to work together to bring
      microbiology into the classroom. Journal of Microbiology & Biology Education. 

PMID- 27047586
TI  - Crowdfunding Campaigns Help Researchers Launch Projects and Generate Outreach.
AB  - Organizers of participatory research (citizen science) projects can generate
      funds and outreach through crowdfunding. Here we provide insights from three
      successful science crowdfunding campaigns recently completed on Indiegogo,
      Experiment, and Kickstarter. Choosing a crowdfunding platform that fits the
      project is just the beginning; a successful campaign reflects its content,
      management, and marketing, and some researchers may need to acquire new skills.
      In addition, the growing trend of crowdfunding for science reinforces the
      importance of academic engagement with social media. 

PMID- 27047587
TI  - Tools for Citizen-Science Recruitment and Student Engagement in Your Research and
      in Your Classroom.
AB  - The field of citizen science is exploding and offers not only a great way to
      engage the general public in science literacy through primary research, but also
      an avenue for teaching professionals to engage their students in meaningful
      community research experiences. Though this field is expanding, there are many
      hurdles for researchers and participants, as well as challenges for teaching
      professionals who want to engage their students. Here we highlight one of our
      projects that engaged many citizens in Raleigh, NC, and across the world, and we
      use this as a case study to highlight ways to engage citizens in all kinds of
      research. Through the use of numerous tools to engage the public, we gathered
      citizen scientists to study skin microbes and their associated odors, and we
      offer valuable ideas for teachers to tap into resources for their own students
      and potential citizen-science projects. 

PMID- 27047588
TI  - Building Research Integrity and Capacity (BRIC): An Educational Initiative to
      Increase Research Literacy among Community Health Workers and Promotores.
AB  - While citizen science is gaining attention of late, for those of us involved in
      community-based public health research, community/citizen involvement in research
      has steadily increased over the past 50 years. Community Health Workers (CHWs),
      also known as Promotores de Salud in the Latino community, are critical to
      reaching underserved populations, where health disparities are more prevalent.
      CHWs/Promotores provide health education and services and may also assist with
      the development and implementation of community- and clinic-based research
      studies. Recognizing that CHWs typically have no formal academic training in
      research design or methods, and considering that rigor in research is critical to
      obtaining meaningful results, we designed instruction to fill this gap. We call
      this educational initiative "Building Research Integrity and Capacity" or BRIC.
      The BRIC training consists of eight modules that can be administered as a self
      paced training or incorporated into in-person, professional development geared to
      a specific health intervention study. While we initially designed this culturally
      grounded, applied ethics training for Latino/Hispanic community research
      facilitators, BRIC training modules have been adapted for and tested with non
      Latino novice research facilitators. This paper describes the BRIC core content
      and instructional design process. 

PMID- 27047589
TI  - Turning Participatory Microbiome Research into Usable Data: Lessons from the
      American Gut Project.
AB  - The role of the human microbiome is the subject of continued investigation
      resulting in increased understanding. However, current microbiome research has
      only scratched the surface of the variety of healthy microbiomes. Public
      participation in science through crowdsourcing and crowdfunding microbiome
      research provides a novel opportunity for both participants and investigators.
      However, turning participatory science into publishable data can be challenging.
      Clear communication with the participant base and among researchers can
      ameliorate some challenges. Three major aspects need to be considered:
      recruitment and ongoing interaction, sample collection, and data analysis. Usable
      data can be maximized through diligent participant interaction, careful survey
      design, and maintaining an open source pipeline. While participatory science will
      complement rather than replace traditional avenues, it presents new opportunities
      for studies in the microbiome and beyond. 

PMID- 27047590
TI  - Addressing Common Student Technical Errors in Field Data Collection: An Analysis
      of a Citizen-Science Monitoring Project.
AB  - The scientific value of citizen-science programs is limited when the data
      gathered are inconsistent, erroneous, or otherwise unusable. Long-term monitoring
      studies, such as Our Project In Hawai'i's Intertidal (OPIHI), have clear and
      consistent procedures and are thus a good model for evaluating the quality of
      participant data. The purpose of this study was to examine the kinds of errors
      made by student researchers during OPIHI data collection and factors that
      increase or decrease the likelihood of these errors. Twenty-four different types
      of errors were grouped into four broad error categories: missing data,
      sloppiness, methodological errors, and misidentification errors. "Sloppiness" was
      the most prevalent error type. Error rates decreased with field trip experience
      and student age. We suggest strategies to reduce data collection errors
      applicable to many types of citizen-science projects including emphasizing neat
      data collection, explicitly addressing and discussing the problems of falsifying
      data, emphasizing the importance of using standard scientific vocabulary, and
      giving participants multiple opportunities to practice to build their data
      collection techniques and skills. 

PMID- 27047591
TI  - Perspectives in Marine Citizen Science.
AB  - Citizen science can be defined as the process by which any non-scientist collects
      data or uses the scientific method under the guidance or mentorship of a
      scientist. This article presents an overview of several marine citizen-science
      projects as practiced by three non-profit organizations. 

PMID- 27047592
TI  - Symbiosis in the Soil: Citizen Microbiology in Middle and High School Classrooms.
AB  - Microorganisms are vital to environmental health, yet their association with
      disease often overshadows these benefits. Building citizen-science activities
      around the positive role of microorganisms and an understanding of their ubiquity
      can begin to dispel misconceptions while simultaneously engaging the public in
      research. Here, we describe a citizen-science microbiology project geared toward
      implementation in middle and high school classrooms. Students culture
      environmental microorganisms and document microbial diversity of plant root
      systems compared with adjacent bulk soil. Results contribute data toward research
      on microbiome recruitment of weeds and other successful plants while addressing
      core topics in science education. 

PMID- 27047593
TI  - Community Partnership Designed to Promote Lyme Disease Prevention and Engagement
      in Citizen Science.
AB  - The goal of this project is to promote Lyme disease prevention and to cultivate
      an interest in science through a citizen-science project coordinated by
      researchers at a public university and teachers at rural high schools. The lesson
      plan is designed to increase student interest in pursuing a science career
      through participation in an authentic research experience, utilizing a topic that
      has implications on the health of the surrounding community. Students are
      introduced in the classroom to zoonotic diseases transmitted by the Ixodes tick,
      the health risks of Lyme disease, and disease prevention strategies. Students
      then participate in a research experience collecting field data and ticks from
      their community, which are used in university research. To measure changes in
      student knowledge and attitudes toward Lyme disease and science careers, students
      completed surveys related to the learning objectives associated with the
      experience. We found participation in the activity increased student confidence
      and ability to correctly differentiate a deer tick from a wood tick and to
      recognize the symptoms of Lyme disease. In addition, students reported increased
      interest in pursuing a science degree in college or graduate school. Authentic
      research experience related to a disease relevant to the local community is
      effective at enhancing high school student engagement in science. 

PMID- 27047594
TI  - The Search for Violacein-Producing Microbes to Combat Batrachochytrium
      dendrobatidis: A Collaborative Research Project between Secondary School and
      College Research Students.
AB  - In this citizen science-aided, college laboratory-based microbiology research
      project, secondary school students collaborate with college research students on
      an investigation centered around bacterial species in the local watershed. This
      study specifically investigated the prevalence of violacein-producing bacterial
      isolates, as violacein has been demonstrated as a potential bioremediation
      treatment for outbreaks of the worldwide invasive chytrid, Batrachochytrium
      dendrobatidis (Bd). The impact of this invasion has been linked to widespread
      amphibian decline, and tracking of the spread of Bd is currently ongoing.
      Secondary school students participated in this research project by sterilely
      collecting water samples from a local watershed, documenting the samples, and
      completing the initial sample plating in a BSL1 environment. In the second phase
      of this project, trained college students working in courses and as research
      assistants in the academic year and summer term in a BSL2 laboratory facility
      were able to use physiological, biochemical, and molecular techniques to further
      identify individual isolates as well as characterize their properties.
      Collaboration between these learning spaces provides an increased interest in the
      community for environmentally relevant research projects and allows for an
      expansion of the research team to increase study robustness. Journal of
      Microbiology & Biology Education. 

PMID- 27047595
TI  - Elements of Success in Chicago Botanic Garden's Science Career Continuum.
AB  - The Science Career Continuum at the Chicago Botanic Garden is a model program for
      successfully encouraging youth from diverse backgrounds into STEM careers. This
      program has shown that when students are given an opportunity to participate in
      real scientific research under the mentorship of a caring professional over
      multiple years, they are more likely to go to college and pursue STEM careers
      than their peers. Journal of Microbiology & Biology Education. 

PMID- 27047596
TI  - Engaging Rural Appalachian High School Girls in College Science Laboratories to
      Foster STEM-Related Career Interest.
AB  - Setting students on a path to success in careers in science is a challenge in
      poor rural Appalachian public schools. Students face many socioeconomic
      obstacles. Their teachers are also limited by many factors including inadequate
      facilities, under-funding, geographical isolation of the schools, and state
      testing constraints. Additionally, students and teachers lack the availability of
      outside science educational opportunities. In an effort to address this
      situation, 24 academically strong high school junior girls and their teachers
      from the Carter County School System in rural east Tennessee were invited for a
      laboratory day at Milligan College, a small liberal arts college in the heart of
      the county. Science faculty, female science majors, and admissions staff
      volunteered in service to the project. The event included three laboratory
      sessions, lunch in the college cafeteria, and campus tours. This successful
      example, as evidenced by positive evaluations by the invited girls and their
      teachers, of educational outreach by a local, small liberal arts college to a
      rural county school system provides a model for establishing a relationship
      between higher education institutions and these underprivileged schools, with the
      intention of drawing more of these poor, rural Appalachian students, particularly
      girls, into a science, technology, engineering, and mathematics (STEM) career
      path. Journal of Microbiology & Biology Education. 

PMID- 27047597
TI  - The First Three Years of a Community Lab: Lessons Learned and Ways Forward.
AB  - The highly specialized nature of scientific research has erected substantial
      barriers between professional scientists and the laity, who have become distanced
      from the process of discovery. The Do-It-Yourself Biology movement seeks to
      remove these impediments, with community laboratories serving as vehicles for
      public engagement and participation in scientific inquiry. We describe our
      experience establishing and maintaining the BUGSS community lab in Baltimore.
      While each community lab is distinct in its structure, culture, and programming,
      we hope that this review of our experience will serve as a resource to inform
      those who seek to understand this growing movement and those who plan to
      establish their own community labs. 

PMID- 27047598
TI  - Learning through Teaching: A Microbiology Service-Learning Experience.
AB  - Service learning is defined as a strategy in which students apply what they have
      learned in the classroom to a community service project. Many educators would
      agree that students often learn best through teaching others. This premise was
      the motivation for a new service-learning project in which undergraduate
      microbiology students developed and taught hands-on microbiology lessons to local
      elementary school children. The lessons included teaching basic information about
      microbes, disease transmission, antibiotics, vaccines, and methods of disease
      prevention. This service-learning project benefitted the college students by
      enforcing their knowledge of microbiology and provided them an opportunity to
      reach out to children within their community. This project also benefitted the
      local schools by teaching the younger students about microbes, infections, and
      handwashing. In this paper, I discuss the development and implementation of this
      new microbiology service-learning project, as well as the observed impact it had
      on everyone involved. 

PMID- 27047599
TI  - Student-Designed Service-Learning Projects in an Undergraduate Neurobiology
      Course.
AB  - One of the challenges in teaching a service-learning course is obtaining student
      buy-in from all students in the course. To circumvent this problem, I have let
      students in my undergraduate Neurobiology course design their own service
      learning projects at the beginning of the semester. Although this can be chaotic
      because it requires last-minute planning, I have made it successful through
      facilitating student communication in the classroom, requiring thorough project
      proposals, meeting with students regularly, and monitoring group progress through
      written reflection papers. Most of my students have strong opinions about the
      types of projects that they want to carry out, and many students have used
      connections that they have already made with local organizations. Almost all
      projects that students have designed to this point involve teaching basic
      concepts of neurobiology to children of various ages while simultaneously
      sparking their interest in science. Through taking ownership of the project and
      designing it such that it works well with their strengths, interests, and weekly
      schedule, students have become more engaged in service learning and view it as a
      valuable experience. Despite some class time being shifted away from more
      traditional assignments, students have performed equally well in the course, and
      they are more eager to talk with others about course concepts. Furthermore, the
      feedback that I have received from community partners has been excellent, and
      some students have maintained their work with the organizations. 

PMID- 27047600
TI  - A Progressive Reading, Writing, and Artistic Module to Support Scientific
      Literacy.
AB  - Scientific literacy, marked by the ability and willingness to engage with
      scientific information, is supported through a new genre of citizen science
      course-based research in association with undergraduate laboratories. A three
      phased progressive learning module was developed to enhance student engagement in
      such contexts while supporting three learning outcomes: I) present an argument
      based on evidence, II) analyze science and scientists within a social context,
      and III) experience, reflect upon, and communicate the nature of scientific
      discovery. Phase I entails guided reading and reflection of citizen science
      themed texts. In Phase II, students write, peer-review, and edit position and
      counterpoint papers inspired by the following prompt, "Nonscientists should do
      scientific research." Phase III involves two creative assignments intended to
      communicate the true nature of science. Students work collaboratively to develop
      public service announcement-like poster campaigns to debunk a common
      misconception about the nature of science or scientists. Individually, they
      create a work of art to communicate a specific message about the raw experience
      of performing scientific research. Suggestions for implementation and
      modifications are provided. Strengths of the module include the development of
      transferable skills, temporal distribution of grading demands, minimal in-class
      time needed for implementation, and the inclusion of artistic projects to support
      affective learning domains. This citizen science-themed learning module is an
      excellent complement to laboratory coursework, as it serves to surprise,
      challenge, and inspire students while promoting disciplinary values. 

PMID- 27047601
TI  - Adapting an Infectious Diseases Course for "Engaged Citizen" Themes.
AB  - This article describes philosophies and perspectives underpinning scientific
      citizenship-focused curricular changes implemented into a pre-existing
      undergraduate infectious diseases course. Impetus for the curricular changes was
      a novel, campus-wide, multidisciplinary "Engaged Citizen" theme for the general
      education curriculum. The first half of the article describes the larger contexts
      from which the curricular changes were borne and the resulting instructional
      model. The second half of the article shares both student and instructor
      perspectives on the curricular changes and potential application of the model to
      other science courses. 

PMID- 27047602
TI  - The Use of Online Citizen-Science Projects to Provide Experiential Learning
      Opportunities for Nonmajor Science Students.

PMID- 27047603
TI  - Creating Critical Consumers of Health and Science News: Teaching Science to the
      Non-Scientist Using Newsworthy Topics in the Life Sciences.
AB  - Scientists constantly make groundbreaking discoveries, some of which receive
      attention from the press. We designed a course intended for a lay audience that
      provides the scientific background to appreciate these reports more fully. We
      discuss three topics in the life sciences: stem cells, cancer, and infectious
      disease. The course is structured to blend relevant scientific background and
      evaluation of primary literature with the coverage of these advances by the media
      and popular press. In short, lectures emphasize exposure to basic biological
      concepts and tools as a means of informing understanding of prominent biological
      questions of public interest. The overall goal of the course is not only to
      expose students to the media's coverage of scientific progress, but also to hone
      their critical thinking skills to distinguish hope from hype. 

PMID- 27047604
TI  - Controversy in Biology Classrooms-Citizen Science Approaches to Evolution and
      Applications to Climate Change Discussions.
AB  - The biological sciences encompass topics considered controversial by the American
      public, such as evolution and climate change. We believe that the development of
      climate change education in the biology classroom is better informed by an
      understanding of the history of the teaching of evolution. A common goal for
      science educators should be to engender a greater respect for and appreciation of
      science among students while teaching specific content knowledge. Citizen science
      has emerged as a viable yet underdeveloped method for engaging students of all
      ages in key scientific issues that impact society through authentic data-driven
      scientific research. Where successful, citizen science may open avenues of
      communication and engagement with the scientific process that would otherwise be
      more difficult to achieve. Citizen science projects demonstrate versatility in
      education and the ability to test hypotheses by collecting large amounts of often
      publishable data. We find a great possibility for science education research in
      the incorporation of citizen science projects in curriculum, especially with
      respect to "hot topics" of socioscientific debate based on our review of the
      findings of other authors. Journal of Microbiology & Biology Education. 

PMID- 27047605
TI  - Real Life Science with Dandelions and Project BudBurst.
AB  - Project BudBurst is a national citizen-science project that tracks bloom times
      and other phenological data for plants across the country. Data from Project
      BudBurst are being used to measure the effects of climate change. Students can
      participate in this project by watching any of the plants on the list, including
      the common dandelion, which makes the program easy and accessible to everyone.
      Journal of Microbiology & Biology Education. 

PMID- 27047606
TI  - Using Citizen Science to Engage Introductory Students: From Streams to the Solar
      System.
AB  - We present two examples of citizen science learning activities, with discussion
      of how these activities align with teaching strategies shown to increase
      retention of under-represented minorities and improve learning for all students
      in science. For introductory science students from diverse backgrounds, citizen
      science provides a unique hands-on opportunity to engage students in the process
      of scientific discovery and to contribute to real science through their
      curriculum. These tools also increase engagement of science majors and address
      the current national priority of increasing student retention in science,
      technology, engineering, and mathematics (STEM) fields. 

PMID- 27047607
TI  - Incorporating Primary Scientific Literature in Middle and High School Education.
AB  - Primary literature is the most reliable and direct source of scientific
      information, but most middle school and high school science is taught using
      secondary and tertiary sources. One reason for this is that primary science
      articles can be difficult to access and interpret for young students and for
      their teachers, who may lack exposure to this type of writing. The Journal of
      Emerging Investigators (JEI) was created to fill this gap and provide primary
      research articles that can be accessed and read by students and their teachers.
      JEI is a non-profit, online, open-access, peer-reviewed science journal dedicated
      to mentoring and publishing the scientific research of middle and high school
      students. JEI articles provide reliable scientific information that is written by
      students and therefore at a level that their peers can understand. For student
      authors who publish in JEI, the review process and the interaction with
      scientists provide invaluable insight into the scientific process. Moreover, the
      resulting repository of free, student-written articles allows teachers to
      incorporate age-appropriate primary literature into the middle and high school
      science classroom. JEI articles can be used for teaching specific scientific
      content or for teaching the process of the scientific method itself. The critical
      thinking skills that students learn by engaging with the primary literature will
      be invaluable for the development of a scientifically-literate public. 

PMID- 27047608
TI  - Using Scavenger Hunts to Familiarize Students with Scientific Journal Articles.
AB  - Primary scientific literature can be difficult to navigate for anyone unfamiliar
      with its foreign, formal structure. We sought to create a fun, easy learning tool
      to help familiarize students of all ages with the structure of a scientific
      article. Our main learning objective was for the student to realize that science
      writing is formulaic-that specific information is found in predictable locations
      within an article-and that, with an understanding of the formula, anyone can
      comfortably navigate any journal article and accurately predict what to expect to
      find in each section. To this end, we designed a Journal Article Scavenger Hunt
      that requires the user to find and identify a series of commonplace features of a
      primary research article. The scavenger hunt activity is quick and easy to
      implement, and is adaptable to various ages and settings, including the
      classroom, lab, and at outreach events. The questions in the scavenger hunt can
      be scaled in difficulty and specificity to suit the instructor's needs. Over many
      years of using this activity, we have received positive feedback from students of
      all ages, from elementary school students to lay adult-learners as well as
      science teachers themselves. By making the unknown seem predictable and
      approachable, the scavenger hunt helps a variety of audiences feel more
      comfortable with science and more confident in their ability to engage directly
      with the scientific literature. Journal of Microbiology & Biology Education. 

PMID- 27047609
TI  - More of an Art than a Science: Using Microbial DNA Sequences to Compose Music.
AB  - Bacteria are everywhere. Microbial ecology is emerging as a critical field for
      understanding the relationships between these ubiquitous bacterial communities,
      the environment, and human health. Next generation DNA sequencing technology
      provides us a powerful tool to indirectly observe the communities by sequencing
      and analyzing all of the bacterial DNA present in an environment. The results of
      the DNA sequencing experiments can generate gigabytes to terabytes of
      information, however, making it difficult for the citizen scientist to grasp and
      the educator to convey this data. Here, we present a method for interpreting
      massive amounts of microbial ecology data as musical performances, easily
      generated on any computer and using only commonly available or freely available
      software and the 'Microbial Bebop' algorithm. Using this approach, citizen
      scientists and biology educators can sonify complex data in a fun and interactive
      format, making it easier to communicate both the importance and the excitement of
      exploring the planet earth's largest ecosystem. 

PMID- 27047610
TI  - Games that Enlist Collective Intelligence to Solve Complex Scientific Problems.
AB  - There is great value in employing the collective problem-solving power of large
      groups of people. Technological advances have allowed computer games to be
      utilized by a diverse population to solve problems. Science games are becoming
      more popular and cover various areas such as sequence alignments, DNA base
      pairing, and protein and RNA folding. While these tools have been developed for
      the general population, they can also be used effectively in the classroom to
      teach students about various topics. Many games also employ a social component
      that entices students to continue playing and thereby to continue learning. The
      basic functions of game play and the potential of game play as a tool in the
      classroom are discussed in this article. 

PMID- 27047611
TI  - Equations of the End: Teaching Mathematical Modeling Using the Zombie Apocalypse.
AB  - Mathematical models of infectious diseases are a valuable tool in understanding
      the mechanisms and patterns of disease transmission. It is, however, a difficult
      subject to teach, requiring both mathematical expertise and extensive subject
      matter knowledge of a variety of disease systems. In this article, we explore
      several uses of zombie epidemics to make mathematical modeling and infectious
      disease epidemiology more accessible to public health professionals, students,
      and the general public. We further introduce a web-based simulation, White Zed
      (http://cartwrig.ht/apps/whitezed/), that can be deployed in classrooms to allow
      students to explore models before implementing them. In our experience, zombie
      epidemics are familiar, approachable, flexible, and an ideal way to introduce
      basic concepts of infectious disease epidemiology. 

PMID- 27047612
TI  - Using a Concept Inventory to Assess the Reasoning Component of Citizen-Level
      Science Literacy: Results from a 17,000-Student Study.
AB  - After articulating 12 concepts for the reasoning component of citizen-level
      science literacy and restating these as assessable student learning outcomes
      (SLOs), we developed a valid and reliable assessment instrument for addressing
      the outcomes with a brief 25-item science literacy concept inventory (SLCI). In
      this paper, we report the results that we obtained from assessing the citizen
      level science literacy of 17,382 undergraduate students, 149 graduate students,
      and 181 professors. We address only findings at or above the 99.9% confidence
      level. We found that general education (GE) science courses do not significantly
      advance understanding of science as a way of knowing. However, the understanding
      of science's way of knowing does increase through academic ranks, indicating that
      the extended overall academic experience better accounts for increasing such
      thinking capacity than do science courses alone. Higher mean institutional SLCI
      scores correlate closely with increased institutional selectivity, as measured by
      the institutions' higher mean SAT and ACT scores. Socioeconomic factors of a)
      first-generation student, b) English as a native language, and c) interest in
      commitment to a science major are unequally distributed across ethnic groups.
      These factors proved powerful in accounting for the variations in SLCI scores
      across ethnicities and genders. 

PMID- 27047613
TI  - Citizen Science: The Small World Initiative Improved Lecture Grades and
      California Critical Thinking Skills Test Scores of Nonscience Major Students at
      Florida Atlantic University.
AB  - Course-based undergraduate research is known to improve science, technology,
      engineering, and mathematics student achievement. We tested "The Small World
      Initiative, a Citizen-Science Project to Crowdsource Novel Antibiotic Discovery"
      to see if it also improved student performance and the critical thinking of non
      science majors in Introductory Biology at Florida Atlantic University (a large,
      public, minority-dominant institution) in academic year 2014-15. California
      Critical Thinking Skills Test pre- and posttests were offered to both Small World
      Initiative (SWI) and control lab students for formative amounts of extra credit.
      SWI lab students earned significantly higher lecture grades than control lab
      students, had significantly fewer lecture grades of D+ or lower, and had
      significantly higher critical thinking posttest total scores than control
      students. Lastly, more SWI students were engaged while taking critical thinking
      tests. These results support the hypothesis that utilizing independent course
      based undergraduate science research improves student achievement even in
      nonscience students. 

PMID- 27047614
TI  - MyOSD 2014: Evaluating Oceanographic Measurements Contributed by Citizen
      Scientists in Support of Ocean Sampling Day.
AB  - The first Ocean Sampling Day (OSD) took place on June 21, 2014. In a coordinated
      effort, an internationally distributed group of scientists collected samples from
      marine surface waters in order to study microbial diversity on a single day with
      global granularity. Concurrently, citizen scientists enriched the OSD initiative
      through the MyOSD project, providing additional oceanographic measurements
      crucial to the contextualization of microbial diversity. Clear protocols, a user
      friendly smartphone application, and an online web-form guided citizens in
      accurate data acquisition, promoting quality submissions to the project's
      information system. To evaluate the coverage and quality of MyOSD data
      submissions, we compared the sea surface temperature measurements acquired
      through OSD, MyOSD, and automatic in situ systems and satellite measurements. Our
      results show that the quality of citizen-science measurements was comparable to
      that of scientific measurements. As 79% of MyOSD measurements were conducted in
      geographic areas not covered by automatic in situ or satellite measurement,
      citizen scientists contributed significantly to worldwide oceanographic data
      gathering. Furthermore, survey results indicate that participation in MyOSD made
      citizens feel more engaged in ocean issues and may have increased their
      environmental awareness and ocean literacy. 

PMID- 27047615
TI  - Crowdsourced Data Indicate Widespread Multidrug Resistance in Skin Flora of
      Healthy Young Adults.
AB  - In a laboratory exercise for undergraduate biology majors, students plated
      bacteria from swabs of their facial skin under conditions that selected for
      coagulase-negative Staphylococcus; added disks containing the antibiotics
      penicillin, oxacillin, tetracycline, and erythromycin; and measured zones of
      inhibition. Students also recorded demographic and lifestyle variables and merged
      this information with similar data collected from 9,000 other students who had
      contributed to the database from 2003 to 2011. Minimum inhibitory concentration
      (MIC) testing performed at the Harborview Medical Center Microbiology Laboratory
      (Seattle, WA) indicated a high degree of accuracy for student-generated data;
      species identification with a matrix-assisted laser desorption ionization (MALDI)
      Biotyper revealed that over 88% of the cells analyzed by students were S.
      epidermidis or S. capitus. The overall frequency of resistant cells was high,
      ranging from 13.2% of sampled bacteria resistant to oxacillin to 61.7% resistant
      to penicillin. Stepwise logistic regressions suggested that recent antibiotic use
      was strongly associated with resistance to three of the four antibiotics tested
      (p = 0.0003 for penicillin, p << 0.0001 for erythromycin and tetracycline), and
      that age, gender, use of acne medication, use of antibacterial soaps, or makeup
      use were associated with resistance to at least one of the four antibiotics.
      Furthermore, drug resistance to one antibiotic was closely linked to resistance
      to the other three antibiotics in every case (all p values << 0.0001), suggesting
      the involvement of multidrug-resistant strains. The data reported here suggest
      that citizen science could not only provide an important educational experience
      for undergraduates, but potentially play a role in efforts to expand antibiotic
      resistance (ABR) surveillance. 

PMID- 27047616
TI  - Implementation challenges of free maternity services policy in Kenya: the health
      workers' perspective.
AB  - INTRODUCTION: Kenya implemented the policy of free maternity services to reduce
      maternal mortality and morbidity. For successful implementation of this policy,
      there is need to monitor the implementation progress, identify the challenges and
      mitigate them and determine better strategies for implementation based on
      emerging implementation issues. This study was carried out to determine the
      challenges facing policy implementation and strategies for better implementation.
      METHODS: This was a cross-sectional descriptive study carried at the Rift Valley
      Provincial General Hospital (RVPGH) and Bondeni maternity. All the staff who work
      at Bondeni Maternity (including nursing officer in-charge) were included in the
      study. All the staff who work at the Maternity Unit of the RVPGH were included in
      the study, as well as the Medical Superintendent of the facility. A total of 110
      respondents were sampled. A questionnaire and interview guide were used to
      collect data. Data was analyzed using SPSS software. RESULTS: A response rate of
      91% (n=100) was achieved. Major implementation challenges include inadequate
      supplies (86%), inadequate funding (38%), staff shortage (92%), lack of
      motivation among health workers (62%), overwhelming workload (89%) and abuse of
      services by clients (32%). Strategies for better implementation include
      employment of more staff, motivation of health workers, improvement in policy
      financing, training of health workers and provision of adequate supplies.
      CONCLUSION: Implementation of free maternity services policy in Kenya is facing
      challenges but there exists strategies, which, if implemented, will help address
      these challenges.

PMID- 27047617
TI  - [Arteria lusoria associated with bicarotid trunk: about a case and review of the
      literature].

PMID- 27047618
TI  - Bronchiectasis: a bacteriological profile.
AB  - The occurrence of bronchiectasis can involve a combination of many environmental
      factors, including infection. The aim of our work is to determine the
      bacteriological profile of bronchiectasis. This is a retrospective study of 100
      patients hospitalized in between January 2010 and July 2013. The average age was
      48 years with a 58% female predominance. Symptomatology was by a bronchial
      syndrome in 90% of cases. Bacteriological examination was able to isolate the
      microbe in 35% of cases. In our study it was through the examination of sputum
      cytology in 27% of cases, through the examination of liquid bronchial aspiration
      in 5% of cases, and through direct examination of sputum in search of
      Mycobacterium tuberculosis in 3% of cases. Microbes isolated were: Streptococcus
      pneumonia in 11 cases; Pseudomonas aeruginosa in 10 cases, Klebsiella pneumonia
      and Mycobacterium tuberculosis in 3 cases each; Moraxella catarrhalis,
      Haemophilus influenzae, Escherichia coli, Citrobacter spp, Serratia marcescens,
      Mycoplasma pneumoniae, Acinetobacter baumannii and Staphylococcus aureus in one
      case each. Through this work, the authors highlight that Streptococcus pneumoniae
      and Pseudomonas aeruginosa are the most commonly- identified microbes in their
      patients. It is necessary to have a full bacterial examination and to repeat it
      regularly over the course of the bronchiectasis. 

PMID- 27047619
TI  - [Anesthesia for total hip prosthesis: report of 50 cases].

PMID- 27047620
TI  - HIV knowledge and risky sexual behavior among men in Rwanda.
AB  - INTRODUCTION: New infections of Human Immunodeficiency Virus (HIV) remain a big
      problem in many countries. Different interventions have been implemented to
      improve the general knowledge of HIV, with the hypothesis that increasing HIV
      knowledge will reduce risky sexual behavior (RSB). However, HIV knowledge may not
      necessarily reduce RSB. This study explores HIV knowledge and its effect on RSB.
      METHODS: The study used data from the 2005 and 2010 Rwanda Demographic and Health
      Surveys to analyze the association between HIV risk factors and two types of RSB
      (having two or more partners in the past 12 months; and among those with two or
      more partners, not using a condom at last sex) and the association between HIV
      knowledge and those RSB. Multivariate logistic regression was used to determine
      predictors of RSB. RESULTS: Among 2,773 men in 2005 and 3,772 men in 2010, 5% and
      7% respectively reported having two or more sexual partners. Among them, 93% in
      2005 and 74% in 2010 did not use a condom at the last sex. Between 2005 and 2010,
      knowledge of the protective effect of having just one uninfected faithful
      partner, and basic knowledge of HIV decreased. Knowledge of the protective effect
      of using condoms increased from 90% to 94%. However, HIV knowledge was not
      associated with either type of RSB. CONCLUSION: In setting up policies and
      strategies related to HIV prevention, policymakers should consider that focusing
      on HIV knowledge is not sufficient in itself.

PMID- 27047621
TI  - Video-laryngoscopy introduction in a Sub-Saharan national teaching hospital:
      luxury or necessity?
AB  - Tracheal intubation using Macintosh blade is the technique of choice for the
      liberation of airways. It can turn out to be difficult, causing severe
      complications which can entail the prognosis for survival or the adjournment of
      the surgical operation. The video-laryngoscope allows a better display of the
      larynx and a good exposure of the glottis and then making tracheal intubation
      simpler compared with a conventional laryngoscope. It is little spread in sub
      Saharan Africa and more particularly in Burkina Faso because of its high cost. We
      report our first experiences of use of the video-laryngoscope through two cases
      of difficult tracheal intubation which had required the adjournment of the
      interventions. It results that the video-laryngoscope makes tracheal intubation
      easier even in it's the first use because of the good glottal display which it
      gives and because its allows apprenticeship easy. Therefore, it is not a luxury
      to have it in our therapeutic arsenal. 

PMID- 27047622
TI  - [Squamous cell carcinoma of the gallbladder: report of a case].

PMID- 27047623
TI  - [Bilateral central fracture dislocation of both hips].

PMID- 27047624
TI  - [Sciatic paralysis following a traumatic loosening of the hip prosthesis].

PMID- 27047626
TI  - [Retrorectal vestigial cyst: a report of a case].

PMID- 27047625
TI  - [Evaluation of venous thromboembolic risk and thromboprophylaxis practice in
      internal medicine].

PMID- 27047627
TI  - [Skin metastases seen at the pathology laboratory in Lome, Togo, between 2005 and
      2014].

PMID- 27047628
TI  - [Sporadic duodenal gastrinoma].

PMID- 27047630
TI  - Long-term Efficacy of Micro-focused Ultrasound with Visualization for Lifting and
      Tightening Lax Facial and Neck Skin Using a Customized Vectoring Treatment
      Method.
AB  - BACKGROUND: Micro-focused ultrasound with visualization has been cleared by the
      United States Food and Drug Administration to noninvasively lift the eyebrow,
      lift submental and neck tissue, and improve lines and wrinkles of the decollete.
      OBJECTIVE: The objective of this prospective, open-label pilot study was to
      evaluate the efficacy and safety of patient-specific, customized micro-focused
      ultrasound with visualization treatment with vertical vectoring to lift and
      tighten facial and neck tissue. METHODS AND MATERIALS: Subjects 25 to 60 years of
      age (N=20) with areas of skin laxity on the face and neck were enrolled and
      treated. A dual depth treatment was administered using a vectored pattern.
      Subjects were evaluated after 90 days, 180 days, and one year. RESULTS: Overall
      improvements in Subject Global Aesthetic Improvement Scale and Physician Global
      Aesthetic Improvement Scale scores were reported by 90 and 100 percent of
      subjects at 90 and 180 days, respectively, and 95 percent for both measures at
      one year. Six of 14 evaluable subjects were rated as improved by blinded
      assessment at one year. Self-reported improvements maintained for up to one year
      included less sagging (79%), fewer lines and wrinkles (58%), and smoother skin
      texture (47%). CONCLUSION: Based on these results, treatment with micro-focused
      ultrasound with visualization with vertical vectoring demonstrated appreciable
      lifting and tightening of facial and neck tissue resulting in improved Global
      Aesthetic Improvement Scale scores and a high degree of patient satisfaction for
      up to one year. ClinicalTrials.gov Identifier: NCT01708512.

PMID- 27047629
TI  - In-office Painless Aminolevulinic Acid Photodynamic Therapy: A Proof of Concept
      Study and Clinical Experience in More Than 100 Patients.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and pain of in-office "painless"
      aminolevulinic acid photodynamic therapy aimed at decreasing treatment-associated
      pain in patients undergoing removal of actinic keratoses. DESIGN: Prospective
      split-face study comparing short aminolevulinic acid incubation times of 15
      minutes followed by extended exposure (60 minutes) of continuous blue light
      versus conventional aminolevulinic acid photodynamic therapy. Prospective
      assessment of pain in patients undergoing in-office "painless" aminolevulinic
      acid photodynamic therapy. SETTING: Clinical practice office. PARTICIPANTS: Three
      patients with actinic keratoses participated in the split-face study and 101 in
      the pain assessment study. MEASUREMENTS: Evaluations in the split-face study
      included removal of actinic keratoses, skin temperature, and pain measured on a
      10-point visual analog scale. Pain was assessed using the visual analog scale in
      the pain assessment study. RESULTS: In the split-face study, in-office "painless"
      aminolevulinic acid photodynamic therapy resulted in a 52-percent reduction in
      lesions versus 44 percent for conventional aminolevulinic acid photodynamic
      therapy. Maximum pain scores of in-office "painless" aminolevulinic acid
      photodynamic therapy were all 0 at each time point, and the average score for
      conventional aminolevulinic acid photodynamic therapy was 7. Baseline skin
      temperatures increased from a baseline of 29 to 32 degrees C to 34 to 35 degrees
      C by minute 10 of blue light activation on both sides of the face. RESULTS from
      the pain assessment study indicated no or minimal (scores 0-2) pain in nearly all
      patients who received in-office "painless" aminolevulinic acid photodynamic
      therapy as monotherapy or in combination with 5-fluoruacil or imiquimod used as
      pretreatments. CONCLUSIONS: In-office "painless" aminolevulinic acid photodynamic
      therapy appears to be effective for removing actinic keratoses and is associated
      with little or no pain in nearly all patients. This procedure should be evaluated
      in large-scale controlled trials.

PMID- 27047631
TI  - Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution
      Once-daily Treatment: Impact of Disease Severity and Other Concomitant Associated
      Factors on Selection of Therapy and Therapeutic Outcomes.
AB  - Topical treatment for toenail onychomycosis has been fraught with a long-standing
      reputation of poor efficaey, primarily due to physical properties of the nail
      unit that impede drug penetration. Newer topical agents have been formulated as
      Solution, which appear to provide better therapeutic response in properly
      selected patients. It is important to recognize the impact the effects that
      mitigating and concomitant factors can have on efficaey. These factors include
      disease severity, gender, presence of tinea pedis, and diabetes. This article
      reviews results achieved in Phase 3 pivotal studies with topical efinaconazole
      10% Solution applied once daily for 48 weeks with a focus on how the
      aforementioned factors influenced therapeutic outcomes. It is important for
      clinicians treating patients for onychomycosis to evaluate severity, treat
      concomitant tinea pedis, address control of diabetes if present by encouraging
      involvement of the patient's primary care physician, and consider longer
      treatment courses when clinically relevant. 

PMID- 27047633
TI  - A Novel Technique of Supra Superficial Musculoaponeurotic System Hyaluronic Acid
      Injection for Lower Face Lifting.
AB  - BACKGROUND: Various methods attempting to correct sagging of the lower face focus
      mainly on manipulation of the superficial musculoaponeurotic System. Each
      technique has its own limitation. The authors propose a relatively simple,
      conservative method utilizing hyaluronic acid injection just above the
      superficial musculoaponeurotic System. OBJECTIVE: To address a novel hyaluronic
      injection technique to lift the lower face. METHODS: Details of the injection
      techniques are described. The Position of the hyaluronic acid injected and the
      effect of hyaluronic acid on the superficial musculoaponeurotic System were
      confirmed by ultrasonography in one of the cases. RESULTS: Sonogram images
      demonstrated the location of the injected hyaluronic acid and pressure effect of
      hyaluronic acid on the superficial musculoaponeurotic System, confirming the
      ability to manipulate the superficial musculoaponeurotic System by this injection
      technique. The lifting result of this Single injection technique was immediately
      visible and maintained for at least 26 weeks. CONCLUSION: This is a less
      invasive, reproducible method that provides a sustained face lifting result. The
      authors propose the term "supraSMAS lift" for this novel injection technique.

PMID- 27047634
TI  - Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral
      Ischemia in Rats.
AB  - Previous report has indicated that isosteviol has neuroprotective effects.
      However, isosteviol was administered preventively before ischemia and the
      inclusion criteria were limited. In the present study, a more soluble and
      injectable form of isosteviol sodium (STVNA) was administered intravenously hours
      after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to
      investigate its neuroprotective effects in rats. The rats were assessed for
      neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct
      volume quantification and histology evaluation. STVNA 10 mg.kg(-1) can
      significantly reduce the infarct volumes compared with vehicle in animals
      subjected to tMCAO and is twice as potent as previously reported. Additionally,
      the therapeutic window study showed that STVNA could reduce the infarct volume
      compared with the vehicle group when administered 4 hours after reperfusion. A
      similar effect was also observed in animals treated 4 hours after pMCAO.
      Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment
      significantly reduced neurobehavioral impairments. The number of restored NeuN
      labeled neurons was increased and the number of TUNEL positive cells was reduced
      in animals that received STVNA treatment compared with vehicle group. All of
      these findings suggest that STVNA might provide therapeutic benefits against
      cerebral ischemia-induced injury. 

PMID- 27047632
TI  - Confetti-like Sparing: A Diagnostic Clinical Feature of Melasma.
AB  - Diagnostic uncertainty when a patient presents with melasma-like Undings can lead
      to suboptimal treatment and inaccurate prognostic expectations. In this study,
      the authors present a unique clinical feature of melasma that they term the
      "Fitzpatrick macule" and test its Utility in establishing diagnostic certainty.
      The "Fitzpatrick macule" is a confetti-like macule of regularly pigmented skin
      located within a larger patch of melasma hyperpigmentation. To test its
      diagnostic Utility, the authors compared clinical photography of known cases of
      melasma with common mimickers, such as poikiloderma of Civatte and solar
      lentiginosis, and determined the positivity rate of the Fitzpatrick macule in
      each scenario. Their results show that 89.1 percent of clinical photographs of
      melasma were positive for the presence of Fitzpatrick macules compared to 1.1
      percent that were negative. In contrast, 37.5 and 56.3 percent of clinical
      photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick
      macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a
      77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity
      of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In
      summary, the authors report a highly sensitive and specific clinical feature of
      melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules
      may aid in establishing a diagnosis of melasma. 

PMID- 27047635
TI  - Complex Meniscus Tears Treated with Collagen Matrix Wrapping and Bone Marrow
      Blood Injection: A 2-Year Clinical Follow-Up.
AB  - OBJECTIVE: To collect and analyze the 2-year follow-up clinical and MRI results
      of patients treated with an arthroscopic technique of collagen membrane-based
      meniscus repair. DESIGN: 53 consecutive patients with combined (horizontal and
      radial or longitudinal component) and complex meniscal tears (tear extended
      through avascular zones or/and composed with two or more morphological tear
      pattern) were treated with an "all-inside" arthroscopic suture of meniscus and
      wrapping with a collagen membrane (Chondro-Gide) technique with bone marrow blood
      injection. The IKDC 2000 subjective score, IKDC 2000 clinical evaluation score,
      Lysholm score and Barret clinical criteria of meniscal healing were recorded. All
      patients were examinated by MRI 2 years postoperatively, using modified WORMS
      criteria for meniscal integrity. RESULTS: The 2 year follow-up was achieved in 50
      cases. Of these, 2 patients were excluded from the evaluation due to incomplete
      data and 2 patients underwent partial meniscectomy and were classified as
      failures. In 46 patients (86.8% of the intended to treat cases), a statistically
      significant improvement in IKDC 2000 subjective, Lysholm scores and IKDC 2000
      clinical assessment between preoperative and the 2-year follow-up time points
      were obsereved. Barret criteria demonstrated an improved clinical outcome between
      pre- and post-operative values. MRI revealed a non-homogeneous signal without
      meniscal tear (WORMS grade 1) in 76% of the operated menisci (13% WORMS grade 2).
      CONCLUSIONS: The 2-year follow-up data demonstrate that this technique is safe
      and can offer an additional tool to save the meniscus in the patients otherwise
      scheduled for meniscal removal. Level of evidence IV.

PMID- 27047637
TI  - Viability of Pathologic Cartilage Fragments as a Source for Autologous
      Chondrocyte Cultures.
AB  - OBJECTIVE: To study if a culture of chondrocytes can be obtained from pathologic
      hyaline cartilage (PHC) fragments. DESIGN: Twenty-five men and 9 women with
      osteochondritis dissecans (OCD) in 11 cases, arthrosis in 13 patients, and trauma
      in the remaining 10 cases were included. The PHC fragments and a small sample of
      the next healthy cartilage were extracted by arthroscopy. According to the
      appearance, the PHC samples were divided into fixed (3 cases), flapped (6
      patients), or loose bodies (25 cases), depending on the attachment degree of the
      cartilage to the subchondral bone. Approximately half of each pathologic sample
      and the whole healthy one were digested to isolate the cells trying to establish
      the cell culture. RESULTS: We were able to establish a cell culture in 7 out of
      34 (20.6%) PHC samples (positive samples), whereas in the remaining 27 (79.4%) no
      cell growth was observed (negative samples). Most of the negative samples were
      loose bodies (P = 0.005) taken from patients with OCD or arthrosis (P = 0.001)
      with an evolution time of more than 1 year (P < 0.001). The best binary logistic
      regression model (P < 0.001) showed that the only factor affecting the
      establishment of cell culture was the evolution time (P = 0.044). CONCLUSION: It
      is possible to culture chondrocytes from osteochondral fragments if they are
      traumatic, within a year of injury and not from fragments due to arthrosis or
      OCD.

PMID- 27047636
TI  - Patients Scheduled for Chondrocyte Implantation Treatment with MACI Have Larger
      Defects than Those Enrolled in Clinical Trials.
AB  - OBJECTIVE: To compare characteristics for patients scheduled for autologous
      chondrocyte implantation with matrix-assisted chondrocyte implantation (MACI)
      with those enrolled in clinical trials and to describe differences in patient
      selection between countries. DESIGN: Anonymized data from patients scheduled for
      MACI treatment in the knee in Europe and Australia/Asia were obtained from the
      Genzyme/Sanofi database. Average age, defect size, and male-female ratio were
      analyzed and compared by country. Clinical cohort studies and prospective
      comparative trials using autologous chondrocyte implantation and related
      treatments were identified and weighted average age, weighted defect size, and
      male-female ratio were analyzed and compared with data from the database.
      RESULTS: From the database 2,690 patients were included with mean age 33.7 years
      and male-female ratio of 67:33. Mean defect size was 5.64 cm(2) and 70% of the
      defects were 3 to 10 cm(2). There were significant differences between patients'
      mean defect sizes between countries. Sixty-nine studies (57 cohorts and 12
      prospective comparative trials) with a total of 5,449 patients were identified.
      The combined weighted mean age was 34.2 years, and the combined weighted mean
      defect size was 4.89 cm(2). Patients scheduled for MACI had significantly larger
      defects that those included in clinical trials. There was no significant
      difference in age. No differences were found between cohorts and prospective
      comparative trials. CONCLUSION: The vast majority of patients scheduled for
      autologous chondrocyte implantation with MACI have chondral defect comparable to
      that generally recommended, but differences exist between countries. Patients
      enrolled in clinical trials have significantly smaller defects than those
      undergoing treatment outside controlled trials.

PMID- 27047638
TI  - Internal Fixation of Unstable Osteochondritis Dissecans in the Skeletally Mature
      Knee with Metal Screws.
AB  - PURPOSE: Several bioabsorbable and metal options are available for internal
      fixation of an unstable osteochondritis dissecans (OCD) lesion, but currently
      there are little data on outcomes with metal headless compression screws in the
      adult knee. The purpose of this study was to determine (1) the radiographic
      healing rates, (2) midterm clinical outcomes, and (3) comparison between healed
      and unhealed OCD fragments after use of headless metal compression screws for the
      treatment of unstable OCD lesions in the knees of skeletally mature patients.
      METHODS: Retrospective chart review for all skeletally mature patients who
      presented with unstable femoral condyle OCD lesions of the knee was conducted.
      All patients underwent open or arthroscopic reduction and internal fixation using
      headless metal compression screws. Preoperative and postoperative radiographs
      were reviewed with healing defined as radiographic evidence of union of the OCD
      progeny fragment with the condyle. Clinical outcome data were collected
      retrospectively using 3 validated outcome scores: International Knee
      Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score
      (KOOS), and Marx. RESULTS: Twenty-two knees in 22 patients with a mean age of 21
      years (range= 14-37 years) were followed for an average of 8.7 years (range = 2
      22 years). Metal, headless, cannulated compression screws were used in all 22
      cases. At a mean of 31 months postoperatively (range = 2-262), fragment union was
      observed in 18 knees (82%). The remaining 4 knees (18%) required loose fragment
      excision and hardware removal at a mean of 9 months (range = 2-16 months)
      postoperatively. Mean postoperative Marx score was 7 (range = 0-16), the mean
      postoperative IKDC score was 85 (range = 62-100), and mean KOOS scores included
      KOOS Pain (93; range = 69-100), KOOS Symptoms (86; range = 71-100), KOOS ADL (98;
      range = 90-100), KOOS Sports (82; range = 50-100), and KOOS QOL (76; range = 50
      100). CONCLUSION: Headless metal compression screws provide a satisfactory union
      rate for treatment of unstable OCD lesions of the femoral condyles in skeletally
      mature patients. Patients achieving union have good knee function, maintain
      satisfactory activity levels, and have superior knee outcomes compared with those
      that failed to heal after fixation at mid to long-term follow-up.

PMID- 27047639
TI  - Regional Differential Genetic Response of Human Articular Cartilage to Impact
      Injury.
AB  - OBJECTIVE: Normal physiological movement creates different weightbearing zones
      within a human knee: the medial condyle bearing the highest and the trochlea
      bearing the lowest weight. Adaptation to different physiological loading
      conditions results in different tissue and cellular properties within a knee. The
      objective of this study was to use microarray analysis to examine gene expression
      differences among three anatomical regions of human knee articular cartilage at
      baseline and following induction of an acute impact injury. DESIGN: Cartilage
      explants were harvested from 7 cadaveric knees (12 plugs per knee). A drop tower
      was utilized to introduce injury. Plugs were examined 24 hours after impact for
      gene expression using microarray. The primary analysis is the comparison of
      baseline versus impacted samples within each region separately. In addition,
      pairwise comparisons among the three regions were performed at baseline and after
      impact. False discovery rate (FDR) was used to evaluate significance of
      differential gene expression. RESULTS: In the comparison of before and after
      injury, the trochlear had 130 differentially expressed genes (FDR <= 0.05) while
      the condyles had none. In the comparison among regions, smaller sets of
      differentially expressed genes (n <= 21) were found, with trochlea being more
      different than the condyles. Most of more frequently expressed genes in trochlea
      are developmental genes. CONCLUSIONS: Within the experimental setup of this
      study, only the trochlea was displaying an acute genetic response on injury. Our
      data demonstrated the regional-specific response to injury in human articular
      cartilage.

PMID- 27047640
TI  - Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair
      in a Mini-Pig Model.
AB  - OBJECTIVE: We have recently shown that mesenchymal stem cells (MSCs) embedded in
      a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming
      growth factor-beta3 [TGF-beta3]) produce a cartilage-like tissue in vitro. The
      current objective was to determine if these same factors could be combined
      immediately prior to implantation to induce a superior healing response in vivo
      relative to the hydrogel alone. DESIGN: Trochlear chondral defects were created
      in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel
      alone and hydrogels containing allogeneic MSCs, TGF-beta3, or both. Six weeks
      after surgery, micro-computed tomography was used to quantitatively assess defect
      fill and subchondral bone remodeling. The quality of cartilage repair was
      assessed using the ICRS-II histological scoring system and immunohistochemistry
      for type II collagen. RESULTS: Treatment with TGF-beta3 led to a marked increase
      in positive staining for collagen type II within defects (P < 0.05), while
      delivery of MSCs did not (P > 0.05). Neither condition had an impact on other
      histological semiquantitative scores (P > 0.05), and inclusion of MSCs led to
      significantly less defect fill (P < 0.05). For all measurements, no synergistic
      interaction was found between TGF-beta3 and MSC treatment when they were
      delivered together (P > 0.05). CONCLUSIONS: At this early healing time point,
      treatment with TGF-beta3 promoted the formation of collagen type II within the
      defect, while allogeneic MSCs had little benefit. Combination of TGF-beta3 and
      MSCs at the time of surgery did not produce a synergistic effect. An in vitro
      precultured construct made of these components may be required to enhance in vivo
      repair in this model system.

PMID- 27047641
TI  - Correlation Analysis of SOX9, -5, and -6 as well as COL2A1 and Aggrecan Gene
      Expression of Collagen I Implant-Derived and Osteoarthritic Chondrocytes.
AB  - OBJECTIVE: Matrix-assisted autologous chondrocyte implantation is frequently
      applied to replace damaged cartilage in order to support tissue regeneration or
      repair and to prevent progressive cartilage degradation and osteoarthritis. Its
      application, however, is limited to primary defects and contraindicated in the
      case of osteoarthritis that is partially ascribed to dedifferentiation and
      phenotype alterations of chondrocytes obtainable from patients' biopsies. The
      differentiation state of chondrocytes is reflected at the level of structural
      gene (COL2A1, ACAN, COL1A1) and transcription factor (SOX9, 5, 6) expression.
      METHODS/DESIGN: We determined the mRNA abundances of COL2A1, ACAN, and COL1A1as
      well as SOX9, -5, and -6 of freshly isolated and passaged collagen I implant
      derived and osteoarthritic chondrocytes via reverse transcription-polymerase
      chain reaction. Moreover, we analyzed the correlation of structural and
      transcription factor gene expression. Thus, we were able to evaluate the impact
      of the mRNA levels of transcription factors on the expression of cartilage
      specific structural genes. RESULTS: Significant differences were obtained (1) for
      freshly isolated osteoarthritic versus collagen I implant-derived chondrocytes,
      (2) due to passaging of the respective cell sources, (3) for osteoarthritic
      versus nonosteoarthritic chondrocytes, and (4) for COL2A1 versus ACAN expression
      with respect to the coherence with SOX9, -5, and -6 transcript levels.
      CONCLUSION: Our results might contribute to a better understanding of the
      transcriptional regulation of structural gene expression of chondrocytes with
      implications for their use in matrix-assisted autologous chondrocyte
      implantation.

PMID- 27047642
TI  - Mapping Chondrocyte Viability, Matrix Glycosaminoglycan, and Water Content on the
      Surface of a Bovine Metatarsophalangeal Joint.
AB  - OBJECTIVE: The purpose of this study was to determine if there were variations in
      chondrocyte viability, matrix glycosaminoglycan (GAG), and water content between
      different areas of the articular surface of a bovine metatarsophalangeal joint, a
      common and reliable source of articular cartilage for experimental study, which
      may compromise the validity of using multiple samples from different sites within
      the joint. METHODS: Nine fresh cadaveric bovine metatarsophalangeal joints were
      obtained. From each joint, 16 osteochondral explants were taken from 4 facets,
      yielding a total of 144 cartilage specimens for evaluation of chondrocyte
      viability, matrix GAG, and water content. A less invasive method for harvesting
      osteochondral explants and for processing the biopsy for the assessment of
      chondrocyte viability was developed, which maintained maximal viability within
      each cartilage explant. RESULTS: There was no significant difference between the
      16 biopsy sites from the different areas of the joint surface with respect to
      chondrocyte viability, matrix GAG and water content. Pooled data of all samples
      from each joint established the baseline values of chondrocyte viability to be
      89.4% +/- 3.8%, 94.4% +/- 2.2%, and 77.9% +/- 7.8%, in the superficial quarter,
      central half, and deep quarter (with regard to depth from the articular surface),
      respectively. The matrix GAG content of bovine articular cartilage was 6.06 +/-
      0.41 MUg/mg cartilage, and the cartilage water content was 72.4% +/- 1.5%. There
      were also no significant differences of these 3 variables between the different
      joints. CONCLUSION: It is thus reasonable to compare biopsies obtained from
      different sites, as a biopsy from one site would be considered representative of
      the whole joint.

PMID- 27047643
TI  - Defining Pre-Osteoarthritis Is Key to Prevention.

PMID- 27047644
TI  - Late Complications in acute Leukemia patients following HSCT: A single center
      experience.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is currently the only
      curative treatment for acute leukemia. As HSCT improves the long-term survival,
      it is necessary to assess the late-onset complications affecting the quality of
      life following HSCT. SUBJECTS AND METHODS: The study included 122 patients (65
      male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from
      fully- matched siblings, unrelated donors and unrelated cord blood donors between
      February 2013 and August 2014 in Shariati Hospital. All study participants were
      over 18 years of age and had the minimum and maximum survival of 2 and 5 years,
      respectively. Patients who received HLA-haploidentical SCT were excluded from the
      study. All allogeneic recipients received busulfan and cyclophosphamide as
      conditioning regimen. Nobody received TBI-based conditioning regimen in this
      study. Patients were evaluated for cardiovascular, vision, psychological,
      endocrine, fertility problems and secondary malignancies one year after
      transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and
      tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12,
      10.5%).Thirty-nine percent of patients had psychological problems, especially
      depression (34%). Cataract was observed in 13% of patients and 34% complained of
      dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of
      the HSCT survivors had experienced fertility before study entry. According to LH
      and FSH levels, 15% and 9% of females had ovarian failure, respectively.
      Testosterone level was less than normal in 49(84%) men and, according to their
      FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary
      gonadal dysfunction. CONCLUSION: The results showed that patients who received
      Bu/Cy conditioning regimen experienced fewer late side effects such as cataract
      formation and hypothyroidism, compared to previous studies using TBI-based
      conditioning regimen.

PMID- 27047645
TI  - Hematological and biochemical status of Beta-thalassemia major patients in
      Bangladesh: A comparative analysis.
AB  - BACKGROUND: Thalassemia is one of the most common hereditary disorders and Beta
      thalassemia major is its severe form. The present study is concerned with the
      analysis of liver function, thyroid function and estimation of critical serum
      ions as well as hematological characteristics in beta-thalassemia patients and
      controls. SUBJECTS AND METHODS: The study included 54 patients with beta
      thalassemia major and 54 healthy individuals matched by sex and age. The activity
      of Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Aspartate
      transaminase (AST) were assessed in order to evaluate the liver function. Serum
      content of iron (Fe), calcium (Ca), magnesium (Mg), sodium (Na) and potassium (K)
      were also estimated. Tri iodothyronine (T3), Thyroxin (T4) and Thyroid
      stimulating hormone (TSH) levels were assessed in order to evaluate the thyroid
      function. Hemoglobin (Hb), ferritin, hematocrit (HCT), mean corpuscular volume
      (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin
      concentration(MCHC), total iron binding capacity (TIBC) and creatinine level were
      also measured. RESULTS: Significantly, higher ALT (P< 0.001), AST (P< 0.05), ALP
      (P< 0.001) activities and lower creatinine (P< 0.001) level in beta-thalassemia
      patients were found in comparison to healthy individuals. Lower serum level of
      calcium (P< 0.05), magnesium (P< 0.05) and higher level of iron (P> 0.05), sodium
      (P> 0.05) and potassium (P > 0.05) have been found in patients in comparison to
      healthy individuals. Hematological parameters like Hb (P< 0.001), ferritin (P<
      0.05), HCT (P< 0.001), MCV (P< 0.05) and MCH (P< 0.05) have been significantly
      reduced in patients except MCHC (P> 0.05). No significant difference was observed
      in thyroid function between patients and control group. CONCLUSIONS: Our study
      demonstrates that beta-thalassemia patients and controls have difference in liver
      function, thyroid function, serum contents of ions and hematological
      characteristics.

PMID- 27047646
TI  - T-cell/Natural killer-cell neoplasms presenting as leukemia- Case series from
      single tertiary care center.
AB  - BACKGROUND: Mature T/ NK-cell neoplasms are a rare group of disorders and their
      presentation as leukemia is even rarer. Most of the previous studies have focused
      on mature B-cell lineage leukemias and there is a paucity of data on mature T/NK
      cell lineage leukemias. We, therefore, planned this study to analyze their
      spectrum, frequency, morphology and immunophenotypic features. SUBJECTS AND
      METHODS: All cases of lymphomas presenting as leukemia over a period of two and a
      half years were evaluated. Detailed analysis of cases with T/NK-cell lineage was
      done for their clinical, hematological and immunophenotypic features. RESULTS: A
      total of 262 cases of mature lymphoid neoplasms presented as leukemia during the
      study period. Of whom, only 8 (3.1%) cases were of T /NK-cell lineage and the
      remaining (96.9%) were of B-cell lineage. Of 8 cases, 4 (50%) had T
      prolymphocytic leukemia, 2 (25%) had chronic lymphoproliferative disorder-
      natural killer cell and 1 (12.5%) case of each T-large granular lymphocytic
      leukemia and hepatosplenic gamma/delta T-NHL. CONCLUSION: T/NK-cell leukemias are
      rare. Along with clinical and morphological features, pattern of immunophenotypic
      markers is vital for their diagnosis and subcategorization.

PMID- 27047647
TI  - Differentiation of Rat bone marrow Mesenchymal stem cells into Adipocytes and
      Cardiomyocytes after treatment with platelet lysate.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are multipotential cells and their
      therapeutic potency is under intense investigation. Studying the effect of
      different induction factors on MSCs could increase our knowledge about the
      differentiation potency of these cells. One of the most important sources of
      these factors in mammalian body is platelet. Platelet lysate (PL) contains many
      growth factors and therefore, it can be used as a differentiation inducer. In the
      present study, the effect of PL on differentiation of rat bone marrow MSCs into
      cardiomyocytes was studied. MATERIALS AND METHODS: To study the differentiation
      inducing effect of PL, MSCs were treated with 2.5, 5 and 10% PL. Early results of
      this study showed that PL in high concentrations (10%) induces adipogenic
      differentiation of MSCs. Therefore, to evaluate differentiation to
      cardiomyocytes, MSCs were cultured in media containing lower levels of PL (2.5%
      and 5%) and then cardiomyogenic differentiation was induced by treatment with 5
      azacytidine. Differentiation of MSCs was evaluated using direct observation of
      beating cells, immunostaining and real-time PCR techniques. RESULTS: The results
      of qPCR showed that treatment with PL alone increased the expression of cardiac
      alpha actinin (CAA) being predictable by earlier observation of beating cells in
      PL-treated groups. The results of staining assays against cardiac alpha actinin
      also showed that there were stained cells in PL-treated groups. CONCLUSION: The
      results of the present study showed that PL is a powerful induction factor for
      differentiation of MSCs into different cell lines such as cardiomyocytes and
      adipocytes.

PMID- 27047648
TI  - A survey on the relationship between serum 25-hydroxy vitamin D level and tumor
      characteristics in patients with breast cancer.
AB  - BACKGROUND: In recent years, epidemiologic and laboratory studies have implied
      that vitamin D deficiency has a role in the pathogenesis of breast cancer. It has
      shown that vitamin D can prevent tumor progression induced by carcinogens and
      inhibit the carcinogenic effects of high fat diet on breast tissue and growth of
      tumor cells. This study aimed to evaluate serum 25-hydroxyvitamin D level and its
      role in relation to tumor characteristics and different stages of disease in
      women with breast cancer. SUBJECT AND METHODS: This is a cross-sectional study on
      200 patients with breast cancer at different stages of the disease. Information
      on age, menstrual status, BMI and tumor characteristics were recorded. Serum 25
      hydroxy vitamin D concentrations were measured by radioimmunoassay (RIA). Mean
      and standard deviation were used to describe the data. Meanwhile, T-test and sum
      of squares test were used to analyze the data. P<0.05 was considered significant.
      RESULTS: Among 200 patients, 47 (23.5%) had severe vitamin D deficiency, 75 (37.5
      %) had mild vitamin D deficiency and 78 (39.0 %) had sufficient vitamin D levels.
      There was a significant correlation between low vitamin D levels and advanced
      stage of breast cancer, particularly in postmenopausal patients. CONCLUSION: It
      seems that lower levels of vitamin D accompany worse clinicopathologic features.
      Thus, treatment of vitamin D deficiency in postmenopausal patients might be of
      great benefits.

PMID- 27047649
TI  - Thalidomide is more efficient than sodium butyrate in enhancing GATA-1 and EKLF
      gene expression in erythroid progenitors derived from HSCs with beta-globin gene
      mutation.
AB  - BACKGROUND: Efficient induction of fetal hemoglobin (HbF) is considered as an
      effective therapeutic approach in beta thalassemia. HbF inducer agents can induce
      the expression of gamma-globin gene and produce high levels of HbF via different
      epigenetic and molecular mechanisms. Thalidomide and sodium butyrate are known as
      HbF inducer drugs. MATERIAL AND METHODS: CD133(+) stem cells were isolated from
      umbilical cord blood of a newborn with minor beta-thalassemia in order to
      evaluate the effects of these two drugs on the in vitro expression of GATA-1 and
      EKLF genes as erythroid transcription factors. CD133(+) stem cells were expanded
      and differentiated into erythroid lineage and then treated with thalidomide and
      sodium butyrate and finally analyzed by quantitative real-time PCR. Statistical
      analysis was performed using student's t-test by SPSS software. RESULTS:
      Thalidomide and sodium butyrate increased GATA-1 and EKLF gene expression,
      compared to the non-treated control (P<0.05). CONCLUSION: Thalidomide was more
      efficient than sodium butyrate in augmenting expression of GATA-1 and EKLF genes.
      It seems that GATA-1 and EKLF have crucial roles in the efficient induction of
      HbF by thalidomide.

PMID- 27047650
TI  - Clinical use of statins in hematopoietic stem cell transplantation: Old drugs and
      new horizons.
AB  - Hydroxymethylglutaryl Co-enzyme A reductase inhibitors, also known as statins,
      are a class of anti-hyperlipidemic agents. These drugs have been employed vastly
      to reduce the morbidity and mortality of cardiovascular disorders. Soon after
      their introduction, benefits other than their primary actions were discovered.
      Along with these pleiotropic properties, a series of mainly favorable effects has
      been proposed in patients intended to undergo hematopoietic stem cell
      transplantation. These actions address some complications encountered by this
      special population such as graft-versus-host disease, efficacy of chemotherapy,
      infections, etc. This review presents the current evidence surrounding these
      issues. 

PMID- 27047651
TI  - Case report of metastatic invasive breast lobular carcinoma to the urinary
      bladder.
AB  - Breast cancer is the most common cancer in women except skin cancer. The common
      metastatic sites include lymph node, lung, liver and bone. However, metastasis to
      the bladder is extremely rare. To our knowledge, this is the first case of breast
      cancer metastasis to urinary bladder in Jordan which is reported. Nine years
      after the initial diagnosis of lobular breast carcinoma, the patient suffered
      from left side leg edema; Ultrasonography and Computed tomography scanning showed
      thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of
      the bladder confirmed metastatic lesion from the breast. In contrast to the
      primary tumor, bladder metastasis showed negative expression of estrogen (ER) and
      progesterone (PR) receptors. However, Her2neu test was negative in both. The
      reported case confirms that bladder metastasis from breast cancer tend to occur
      late after the diagnosis of the primary tumor. Furthermore, bladder metastasis
      can be asymptomatic and heterogeneous in ER and PR expression in comparison with
      the primary tumor. This report supports the need for careful follow-up and early
      intervention whenever such clinical situation is suspected. This report supports
      further evaluation of receptor status at time of metastasis. 

PMID- 27047652
TI  - A patient with Multiple myeloma and Renal cell carcinoma.
AB  - The coexistence of two malignancies is rarely seen. A little association between
      hematologic malignancies especially multiple myeloma and renal cell carcinoma has
      been reported in the recent past. Several case series revealed a bidirectional
      association between these two malignancies which may be due to the common risk
      factors, similar cytokine growth requirements and clinical presentation. Here, we
      aim to describe a patient who had multiple myeloma and in his work up renal cell
      carcinoma was found out incidentally. We would like to create awareness among
      clinicians for the coincidence of Renal cell carcinoma and Multiple myeloma. 

PMID- 27047653
TI  - Developing a web-based SKOS editor.
AB  - BACKGROUND: The Simple Knowledge Organization System (SKOS) was introduced to the
      wider research community by a 2005 World Wide Web Consortium (W3C) working draft,
      and further developed and refined in a 2009 W3C recommendation. Since then, SKOS
      has become the de facto standard for representing and sharing thesauri, lexicons,
      vocabularies, taxonomies, and classification schemes. In this paper, we describe
      the development of a web-based, free, open-source SKOS editor built for the
      development, curation, and management of small to medium-sized lexicons for
      health-related Natural Language Processing (NLP). RESULTS: The web-based SKOS
      editor allows users to create, curate, version, manage, and visualise SKOS
      resources. We tested the system against five widely-used, publicly-available SKOS
      vocabularies of various sizes and found that the editor is suitable for the
      development and management of small to medium-size lexicons. Qualitative testing
      has focussed on using the editor to develop lexical resources to drive NLP
      applications in two domains. First, developing a lexicon to support an Electronic
      Health Record-based NLP system for the automatic identification of pneumonia
      symptoms. Second, creating a taxonomy of lexical cues associated with Diagnostic
      and Statistical Manual of Mental Disorders (DSM-5) diagnoses with the goal of
      facilitating the automatic identification of symptoms associated with depression
      from short, informal texts. CONCLUSIONS: The SKOS editor we have developed is -
      to the best of our knowledge - the first free, open-source, web-based, SKOS
      editor capable of creating, curating, versioning, managing, and visualising SKOS
      lexicons.

PMID- 27047654
TI  - Stability, Scalability, and Reusability of a Volume Efficient Biocatalytic System
      Constructed on Magnetic Nanoparticles.
AB  - This report investigates for the first time stability, scalability, and
      reusability characteristics of a protein nano-bioreactor useful for green
      synthesis of fine chemicals in aqueous medium extracting maximum enzyme
      efficiency. Enzyme catalysts conjugated with magnetic nanomaterials allow easy
      product isolation after a reaction involving simple application of a magnetic
      field. In this study, we examined a biocatalytic system made of peroxidase-like
      myoglobin (Mb), as a model protein, to covalently conjugate with poly(acrylic
      acid) functionalized magnetic nanoparticles (MNPs, 100 nm hydrodynamic diameter)
      to examine the catalytic stability, scalability, and reusability features of this
      bioconjugate. Application of the conjugate was effective for electrochemical
      reduction of organic and inorganic peroxides, and for both peroxide-mediated and
      electrocatalytic oxidation of the protein substrate 2, 2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) with greater turnover rates and product
      yields than Mb prepared in solution or MNP alone. Mb-attached MNPs displayed
      extensive catalytic stability even after 4 months of storage compared to Mb
      present in solution. Five- and ten-fold scale up of MNPs in the bioconjugates
      resulted in two- and four-fold increases in protein-catalyzed oxidation products,
      respectively. Nearly 40% of the initial product was present even after four
      reuses, which is advantageous for synthesizing sufficient products with a minimal
      investment of precious enzymes. Thus, the results obtained in this study are
      highly significant in guiding cost-effective development and efficient multiple
      uses of enzyme catalysts for biocatalytic, electrocatalytic, and biosensing
      applications via magnetic nanomaterials conjugation.

PMID- 27047656
TI  - Proof of principle for bevacizumab activity in desmoid-type fibromatosis.
AB  - BACKGROUND: Desmoid-type fibromatosis (DF) is a rare disease, which often occurs
      in young adults. Medical treatment is an important option in the treatment
      algorithm of DF. Different chemotherapeutic regimens showed clinical activity in
      DF, but overall treatment tolerability remains poor for this patient cohort.
      Novel approaches investigated tyrosine kinase inhibitors in DF, but tolerability
      remained an issue. CASE PRESENTATION: We treated a patient with progressive DF
      after failure of chemotherapy for 1 year with singe agent bevacizumab. He
      achieved a symptomatic and radiologic response while attainning excellent
      tolerability. CONCLUSIONS: This is the first report on single agent bevacizumab
      in DF, which showed both, good tolerability and efficacy in our patient, thereby
      warranting future trials in DF.

PMID- 27047657
TI  - Common environmental chemicals do not explain atopy contrast in the Finnish and
      Russian Karelia.
AB  - BACKGROUND: Atopic allergy is much more common in Finnish compared with Russian
      Karelia, although these areas are geographically and genetically close. To
      explore the role of environmental chemicals on the atopy difference a random
      sample of 200 individuals, 25 atopic and 25 non-atopic school-aged children and
      their mothers, were studied. Atopy was defined as having at least one positive
      skin prick test response to 14 common inhalant and food allergens tested.
      Concentrations of 11 common environmental pollutants were measured in blood
      samples. RESULTS: Overall, the chemical levels were much higher in Russia than in
      Finland, except for 2,2',4,4'-tetra-bromodiphenyl ether (BDE47). In Finland but
      not in Russia, the atopic children had higher concentrations of polychlorinated
      biphenyls and 1,1-Dichloro-2,2-bis-(p-chlorophenyl)-ethylene (DDE) than the non
      atopic children. In Russia but not in Finland, the atopic mothers had higher DDE
      concentrations than the non-atopic mothers. CONCLUSIONS: Higher concentrations of
      common environmental chemicals were measured in Russian compared with Finnish
      Karelian children and mothers. The chemicals did not explain the higher
      prevalence of atopy on the Finnish side.

PMID- 27047655
TI  - Dystrophin-deficient dogs with reduced myostatin have unequal muscle growth and
      greater joint contractures.
AB  - BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose
      inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice
      in which myostatin is knocked out or inhibited postnatally have a less severe
      phenotype with greater total mass and strength and less fibrosis and fatty
      replacement of muscles than mdx mice with wild-type myostatin expression. Dogs
      with golden retriever muscular dystrophy (GRMD) have previously been noted to
      have increased muscle mass and reduced fibrosis after systemic postnatal
      myostatin inhibition. Based partly on these results, myostatin inhibitors are in
      development for use in human muscular dystrophies. However, persisting concerns
      regarding the effects of long-term and profound myostatin inhibition will not be
      easily or imminently answered in clinical trials. METHODS: To address these
      concerns, we developed a canine (GRippet) model by crossbreeding dystrophin
      deficient GRMD dogs with Mstn-heterozygous (Mstn (+/-)) whippets. A total of four
      GRippets (dystrophic and Mstn (+/-)), three GRMD (dystrophic and Mstn wild-type)
      dogs, and three non-dystrophic controls from two litters were evaluated. RESULTS:
      Myostatin messenger ribonucleic acid (mRNA) and protein levels were downregulated
      in both GRMD and GRippet dogs. GRippets had more severe postural changes and
      larger (more restricted) maximal joint flexion angles, apparently due to further
      exaggeration of disproportionate effects on muscle size. Flexors such as the
      cranial sartorius were more hypertrophied on magnetic resonance imaging (MRI) in
      the GRippets, while extensors, including the quadriceps femoris, underwent
      greater atrophy. Myostatin protein levels negatively correlated with relative
      cranial sartorius muscle cross-sectional area on MRI, supporting a role in
      disproportionate muscle size. Activin receptor type IIB (ActRIIB) expression was
      higher in dystrophic versus control dogs, consistent with physiologic feedback
      between myostatin and ActRIIB. However, there was no differential expression
      between GRMD and GRippet dogs. Satellite cell exhaustion was not observed in
      GRippets up to 3 years of age. CONCLUSIONS: Partial myostatin loss may exaggerate
      selective muscle hypertrophy or atrophy/hypoplasia in GRMD dogs and worsen
      contractures. While muscle imbalance is not a feature of myostatin inhibition in
      mdx mice, findings in a larger animal model could translate to human experience
      with myostatin inhibitors.

PMID- 27047659
TI  - Naegleria: a classic model for de novo basal body assembly.
AB  - The amoeboflagellate Naegleria was one of the first organisms in which de novo
      basal body/centriole assembly was documented. When in its flagellate form, this
      single-celled protist has two flagella that are templated by two basal bodies.
      Each of these basal bodies is structurally well conserved, with triplet
      microtubules and well-defined proximal cartwheel structures, similar to most
      other eukaryotic centrioles. The basal bodies are anchored to the nucleus by a
      single, long striated rootlet. The Naegleria genome encodes many conserved basal
      body genes whose expression is induced prior to basal body assembly. Because of
      the rapid and synchronous differentiation from centriole-less amoebae to
      temporary flagellates with basal bodies, Naegleria offers one of the most
      promising systems to study de novo basal body assembly, as well as the mechanisms
      regulating the number of centrioles assembled per cell. 

PMID- 27047658
TI  - Reliability and measurement error of frontal and horizontal 3D spinal motion
      parameters in 219 patients with chronic low back pain.
AB  - BACKGROUND: In order for measurements to be clinically useful, data on
      psychometric conditions such as reliability should be available in the population
      for which the measurements are intended to be used. This study comprises a test
      retest design separated by 7 to 14 days, and evaluates the intra and interrater
      reliability of regional frontal and horizontal spinal motion in 219 chronic LBP
      patients using the CA6000 Spine Motion Analyzer. In addition, it compares these
      results on the frontal and horizontal plane with previously published results on
      the sagittal plane. 219 individuals with chronic mechanical LBP, classified as
      either Quebec Task Force group 1, 2, 3 or 4 were included, and kinematics of the
      lumbar spine were sampled during standardized spinal lateral flexion and rotation
      motion using a 6-df instrumented spatial linkage system. Test-retest reliability
      and measurement error were evaluated using intraclass correlation coefficients
      ICC(1,1) and Bland-Altman limits of agreement (LOAs). RESULTS: The reliability
      analysis based on the whole study sample showed ICC(1,1) coefficients varying
      between 0.68 and 0.73 for the frontal plane and 0.33 and 0.49 for the horizontal
      plane. Relatively wide LOAs were observed for all parameters. Reliability
      measures in patient subgroups ICC(1,1) ranged between 0.55 and 0.81 for the
      frontal plane and 0.28 and 0.69 for the horizontal plane. Greater ICC(1,1)
      coefficients and smaller LOA were observed when patients were examined by the
      same examiner, had a stable pain level between tests, and were male. ROM
      measurements were more reliable in patients with a BMI higher than 30, and
      measurements on patients with LBP and leg pain showed higher reliability and
      smaller measurement error in all parameters except for the jerk index.
      CONCLUSION: Frontal plane measurements obtained using the CA6000 Spine Motion
      Analyzer are sufficiently reliable to be used for group comparisons but not
      individual comparisons. Measurements in the horizontal plane can be used for
      neither group nor individual comparisons.

PMID- 27047660
TI  - The cost of trauma operating theatre inefficiency.
AB  - The National Health Service (NHS) is currently facing a financial crisis with a
      projected deficit of L2billion by the end of financial year 2015/16. As operating
      rooms (OR) are one of the costliest components in secondary care, improving
      theatre efficiency should be at the forefront of efforts to improve health
      service efficiency. The objectives of this study were to characterize the causes
      of trauma OR delays and to estimate the cost of this inefficiency. A 1-month
      prospective single-centre study in St. Mary's Hospital. Turnaround time (TT) was
      used as the surrogate parameter to measure theatre efficiency. Factors including
      patient age, ASA score and presence of surgical and anaesthetic consultant were
      evaluated to identify positive or negative associations with theatre delays.
      Inefficiency cost was calculated by multiplying the time wasted with staff
      capacity costs and opportunity costs, found to be L24.77/minute. The commonest
      causes for increased TT were delays in sending for patients (50%) and problems
      with patient transport to the OR (31%). 461 min of delay was observed in 12 days,
      equivalent to loss of L951.58/theatre/day. Non-statistically significant trends
      were seen between length of delays and advancing patient age, ASA score and
      absence of either a senior clinician or an anaesthetic consultant. Interestingly,
      the trend was not as strong for absence of an anaesthetic consultant. This study
      found delays in operating TT to represent a sizable cost, with potential
      efficiency savings based on TT of L347,327/theatre/year. Further study of a
      larger sample is warranted to better evaluate the identified trends. 

PMID- 27047661
TI  - Nutritional status of children 0-59 months in selected intervention communities
      in northern Ghana from the africa RISING project in 2012.
AB  - BACKGROUND: Poor nutritional status during childhood and its long-term impact on
      economic growth and wellbeing is well known. This study assessed the nutritional
      status of children in selected communities in northern Ghana, to serve as
      baseline data for the Africa Research in Sustainable Intensification for the Next
      Generation (Africa RISING) project that sought to improve farm-household
      nutrition through agriculture. METHODS: A cross-sectional study was conducted
      among children 0-59 months in selected communities in the Northern (Tibali and
      Cheyohi No. 2), Upper West (Goli and Zanko) and Upper East (Bonia and Sambulgu)
      regions of northern Ghana. A pre-tested, semi-structured questionnaire was used
      to obtain information on background characteristics of caregivers and children.
      Weight and height were measured for children following World Health Organization
      (WHO) procedures and transformed into z-scores using the WHO Anthro. RESULTS: All
      the caregivers (522) were females; majority (73.4 %) had no formal education,
      82.7 % were married and 70.5 % engaged in farming. In all, 533 children were
      recruited: Northern region (38.6 %), Upper West (33.4 %) and Upper East (28.0 %).
      Majority (52.5 %) of the children were males. The mean age was 32 +/- 19 months.
      Levels of stunting, underweight and wasting were 27.2, 17.6 and 8.2 %
      respectively. Stunting, underweight and wasting levels increased within the first
      two years of life. Overall, 33.8 % of the children in northern Ghana were
      malnourished; 20.2 % were from the Northern region, 7.0 and 6.8 % were from Upper
      East and Upper West respectively. CONCLUSION: Different forms of malnutrition
      still exist as a public health problem in various communities in northern Ghana
      and need to be curtailed using effective agriculture-nutrition sensitive
      interventions.

PMID- 27047663
TI  - Lipoid congenital adrenal hyperplasia due to STAR mutations in a Caucasian
      patient.
AB  - Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH,
      is most commonly caused by mutations in steroidogenic acute regulatory protein
      (STAR), which is required for the movement of cholesterol from the outer to the
      inner mitochondrial membranes to synthesize pregnenolone. This study was
      performed to evaluate whether the salt-losing crisis and the adrenal inactivity
      experienced by a Scandinavian infant is due to a de novo STAR mutation. The study
      was conducted at the University of North Dakota, the Mercer University School of
      Medicine and the Memorial University Medical Center to identify the cause of this
      disease. The patient was admitted to a pediatric endocrinologist at the Sanford
      Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is
      an autosomal recessive disease, we identified two de novo heterozygous mutations
      (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene,
      causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and
      is not restricted to any specific region of the world. This Scandinavian family
      was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4
      and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells
      supplemented with an electron transport system showed activity similar to the
      background level, which was ~10% of that observed with wild-type (WT) STAR.
      Protein-folding analysis showed that the finger printing of the STAR p.N148K
      mutant is also different from the WT protein. Inherited STAR mutations may be
      more prevalent in some geographical areas but not necessarily restricted to those
      regions. LEARNING POINTS: STAR mutations cause lipoid CAH.This is a pure
      population from a caucasian family.Mutation ablated STAR activity.The mutation
      resulted in loosely folded conformation of STAR.

PMID- 27047662
TI  - Increased expression of A Proliferation-inducing Ligand (APRIL) in lung
      leukocytes and alveolar epithelial cells in COPD patients with non small cell
      lung cancer: a possible link between COPD and lung cancer?
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an
      excessive activation of the adaptive immune system and, in particular,
      uncontrolled expansion of the B-cell pool. One of the key promoters of B cell
      expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly
      linked to non small cell lung cancer (NSCLC) onset and progression previously.
      However, little is known about the expression of APRIL in the lungs of COPD
      patients. METHODS: Using immuno-fluorescence staining, the expression of APRIL
      was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD
      (FEV1 33 +/- 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4
      subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3
      healthy never-smokers. The percentage of B cells, alveolar macrophages (AMs) and
      polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells
      (AECs) that stained positively for APRIL was quantified using epi-fluorescence
      microscopy and image analysis software. RESULTS: The percentage of APRIL
      expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in
      patients having both COPD and NSCLC than in patients with either COPD or NSCLC
      alone, SC or NSC (p < 0.03 for all comparisons). The percentage of APRIL
      expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC
      alone than in patients with COPD alone. The percentage of APRIL-expressing AECs
      (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05
      for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs
      cells was similar in NSC and SC. CONCLUSION: The percentage of APRIL-expressing B
      cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC
      than in patients with COPD or NSCLC alone or control subjects. These findings
      suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and
      possibly to the development of NSCLC in patients with established COPD.

PMID- 27047664
TI  - Juvenile granulosa cell tumour of the ovary presenting with hyperprolactinaemic
      amenorrhoea and galactorrhoea.
AB  - Secondary amenorrhoea and galactorrhoea represent a common endocrine
      presentation. We report a case of an oestrogen-producing juvenile granulosa cell
      tumour (JGCT) of the ovary in a 16-year-old post-pubertal woman with
      hyperprolactinaemia amenorrhoea and galactorrhoea which resolved following
      surgical resection of the tumour. This patient presented with a 9-month history
      of secondary amenorrhoea and a 2-month history of galactorrhoea. Elevated serum
      prolactin at 7081 mIU/l and suppressed gonadotropins (LH <0.1 U/l; FSH <0.1 U/l)
      were detected. Serum oestradiol was significantly elevated at 7442 pmol/l with
      undetectable beta-human chorionic gonadotropin. MRI showed a bulky pituitary with
      no visible adenoma. MRI of the abdomen showed a 4.8 cm mass arising from the
      right ovary with no evidence of metastatic disease. Serum inhibin B was elevated
      at 2735 ng/l. A right salpingo-oophorectomy was performed, and histology
      confirmed the diagnosis of a JGCT, stage International Federation of Gynaecology
      and Obstetrics 1A. Immunohistochemical staining for prolactin was negative. Post
      operatively, oestrogen and prolactin levels were normalised, and she subsequently
      had a successful pregnancy. In summary, we present a case of an oestrogen
      secreting JGCT with hyperprolactinaemia manifesting clinically with galactorrhoea
      and secondary amenorrhoea. We postulate that observed hyperprolactinaemia was
      caused by oestrogenic stimulation of pituitary lactotroph cells, a biochemical
      state analogous to pregnancy. To the best of our knowledge, this is the first
      report of hyperprolactinaemia as a result of excessive oestrogen production in
      the context of a JGCT. LEARNING POINTS: Hyperprolactinaemia with bilateral
      galactorrhoea and secondary amenorrhoea has a wide differential diagnosis and is
      not always caused by a prolactin secreting pituitary adenoma.Significantly
      elevated serum oestradiol levels in the range seen in this case, in the absence
      of pregnancy, are indicative of an oestrogen-secreting tumour.JGCTs are rare
      hormonally active ovarian neoplasms mostly secreting steroid hormones.Serum
      inhibin can be used as a granulosa cell-specific tumour marker.JGCTs have an
      excellent prognosis in the early stages of the disease.

PMID- 27047665
TI  - Obesity trends by industry of employment in the United States, 2004 to 2011.
AB  - BACKGROUND: Obesity is associated with increased morbidity, occupational
      injuries, and premature mortality. Obesity also disproportionately affects blacks
      and socioeconomically disadvantaged workers. However, few studies have evaluated
      national trends of obesity by employment industry overall and especially by race.
      METHODS: To investigate national trends of obesity by employment industry overall
      and by race, we estimated the age-standardized obesity prevalence from 2004 to
      2011. We used direct age-standardization with the 2000 US Census population as
      the standard among 136,923 adults in the US National Health Interview Survey. We
      also estimated prevalence ratios (PRs) for obesity in black women and men
      compared to their white counterparts for each employment industry using adjusted
      Poisson regression models with robust variance. RESULTS: Obesity prevalence
      increased for men and women over the study period across all employment industry
      categories, and the healthcare industry had the highest overall age-standardized
      prevalence (30 %). Black women had a significantly higher obesity prevalence than
      white women across all employment industry categories, ranging from 33 % (95 %
      confidence interval (CI): 1.16,1.52) in Professional/Management to 74 % in
      Education (95 % CI: 1.56,1.93). Obesity prevalence was higher among black than
      white men for Healthcare (PR = 1.39 [1.15,1.69]), Education (PR = 1.39
      [1.17,1.67]), Public Administration (PR = 1.34 [1.20,1.49]), and Manufacturing
      (PR = 1.19 [1.11,1.27]). Differences in obesity prevalence by race were generally
      widest in professional/management occupations. CONCLUSIONS: Obesity trends varied
      substantially overall as well as within and between race-gender groups across
      employment industries. These findings demonstrate the need for further
      investigation of racial and sociocultural disparities in the work-obesity
      relationship to employ strategies designed to address these disparities while
      improving health among all US workers. Further research and interventions among
      workers in industries with an increasing or high prevalence of obesity should be
      prioritized.

PMID- 27047666
TI  - Experimental neurotransplantation treatment for hereditary cerebellar ataxias.
AB  - Hereditary cerebellar degenerations are a heterogeneous group of diseases often
      having a detrimental impact on patients' quality of life. Unfortunately, no
      sufficiently effective causal therapy is available for human patients at present.
      There are several therapies that have been shown to affect the pathogenetic
      process and thereby to delay the progress of the disease in mouse models of
      cerebellar ataxias. The second experimental therapeutic approach for hereditary
      cerebellar ataxias is neurotransplantation. Grafted cells might provide an effect
      via delivery of a scarce neurotransmitter, substitution of lost cells if
      functionally integrated and rescue or trophic support of degenerating cells. The
      results of cerebellar transplantation research over the past 30 years are
      reviewed here and potential benefits and limitations of neurotransplantation
      therapy are discussed. 

PMID- 27047667
TI  - Primary care physicians' perceived barriers and facilitators to conservative care
      for older adults with chronic kidney disease: design of a mixed methods study.
AB  - BACKGROUND: Guideline committees have identified the need for research to inform
      the provision of conservative care for older adults with stage 5 chronic kidney
      disease (CKD) who have a high burden of comorbidity or functional impairment. We
      will use both qualitative and quantitative methodologies to provide a
      comprehensive understanding of barriers and facilitators to care for these
      patients in primary care. OBJECTIVES: Our objectives are to (1) interview primary
      care physicians to determine their perspectives of conservative care for older
      adults with stage 5 CKD and (2) survey primary care physicians to determine the
      prevalence of key barriers and facilitators to provision of conservative care for
      older adults with stage 5 CKD. DESIGN: A sequential exploratory mixed methods
      design was adopted for this study. The first phase of the study will involve
      fundamental qualitative description and the second phase will be a cross
      sectional population-based survey. SETTING: The research is conducted in Alberta,
      Canada. PARTICIPANTS: The participants are primary care physicians with
      experience in providing care for older adults with stage 5 CKD not planning on
      initiating dialysis. METHODS: The first objective will be achieved by undertaking
      interviews with primary care physicians from southern Alberta. Participants will
      be selected purposively to include physicians with a range of characteristics
      (e.g., age, gender, and location of clinical practice). Interviews will be
      recorded, transcribed verbatim, and analyzed using conventional content analysis
      to generate themes. The second objective will be achieved by undertaking a
      population-based survey of primary care physicians in Alberta. The questionnaire
      will be developed based on the findings from the qualitative interviews and pilot
      tested for face and content validity. Physicians will be provided multiple
      options to complete the questionnaire including mail, fax, and online methods.
      Descriptive statistics and associations between demographic factors and barriers
      and facilitators to care will be analyzed using regression models. LIMITATIONS: A
      potential limitation of this mixed methods study is its cross-sectional nature.
      CONCLUSIONS: This work will inform development of clinical resources and tools
      for care of older adults with stage 5 CKD, to address barriers and enable
      facilitators to community-based conservative care.

PMID- 27047668
TI  - What is this duplicate publication thing?

PMID- 27047670
TI  - Foreword.

PMID- 27047669
TI  - What the Papers Say.
AB  - The Journal of Hip Preservation Surgery (JHPS) is not the only place where work
      in the field of hip preservation may be published. Although our aim is to offer
      the best of the best, we continue to be fascinated by work that finds it way into
      journals other than our own. There is much to learn from it so JHPS has selected
      six recent and topical articles for those who seek a brief summary of what is
      taking place in our ever-fascinating world of hip preservation. What you see here
      are the mildly edited abstracts of the original articles, to give them what JHPS
      hopes is a more readable feel. If you are pushed for time, what follows should
      take you no more than 10 min to read. So here goes .... 

PMID- 27047671
TI  - The challenge to improve the response of biomaterials to the physiological
      environment.
AB  - New applications of biomaterials often require advanced structures containing
      synthetic and natural components that are tuned to provide properties unique to a
      specific application. We discuss how structural characteristics of biomaterials,
      especially hydrophilic ones, can be used in conjunction with non-ideal
      thermodynamics to develop advanced medical systems. We show a number of examples
      of biocompatible, intelligent biomaterials that can be used for organ
      replacement, biosensors, precise drug delivery over days or weeks, and
      regenerative medicine. 

PMID- 27047672
TI  - Future challenges in the in vitro and in vivo evaluation of biomaterial
      biocompatibility.
AB  - As the science and engineering of biomaterials continues to expand with increased
      emphasis on the development of nanomaterials and tissue engineering scaffolds,
      emphasis also must be placed on appropriate and adequate approaches to the in
      vivo and in vitro evaluation of biomaterial biocompatibility/biological response
      evaluation. This article presents six topic areas that should be addressed by
      investigators as they move forward in the development of new systems for
      regenerative medicine. Most certainly, there are other areas that require
      attention to detail and a more complete understanding of the strengths and
      weaknesses of various experimental approaches to biomaterial/biological response
      evaluation. The small number of issues addressed in this article is only meant to
      bring to the attention of prospective investigators and authors, the importance
      of the development of adequate and appropriate evaluation techniques that address
      the unique features of biomaterials utilized in the development of new medical
      devices. 

PMID- 27047673
TI  - Opportunities and challenges for the biodegradable magnesium alloys as next
      generation biomaterials.
AB  - In recent years, biodegradable magnesium alloys emerge as a new class of
      biomaterials for tissue engineering and medical devices. Deploying biodegradable
      magnesium-based materials not only avoids a second surgical intervention for
      implant removal but also circumvents the long-term foreign body effect of
      permanent implants. However, these materials are often subjected to an
      uncontrolled and fast degradation, acute toxic responses and rapid structural
      failure presumably due to a localized, too rapid corrosion process. The patented
      Mg-Nd-Zn-based alloys (JiaoDa BioMg [JDBM]) have been developed in Shanghai Jiao
      Tong University in recent years. The alloy series exhibit lower biodegradation
      rate and homogeneous nanophasic degradation patterns as compared with other
      biodegradable Mg alloys. The in vitro cytotoxicity tests using various types of
      cells indicate excellent biocompatibility of JDBM. Finally, bone implants using
      JDBM-1 alloy and cardiovascular stents using JDBM-2 alloy have been successfully
      fabricated and in vivo long-term assessment via implantation in animal model have
      been performed. The results confirmed the reduced degradation rate in vivo,
      excellent tissue compatibility and long-term structural and mechanical
      durability. Thus, this novel Mg-alloy series with highly uniform nanophasic
      biodegradation represent a major breakthrough in the field and a promising
      candidate for manufacturing the next generation biodegradable implants. 

PMID- 27047674
TI  - Can microfluidics address biomanufacturing challenges in drug/gene/cell
      therapies?
AB  - Translation of any inventions into products requires manufacturing. Development
      of drug/gene/cell delivery systems will eventually face manufacturing challenges,
      which require the establishment of standardized processes to produce biologically
      relevant products of high quality without incurring prohibitive cost.
      Microfluidicu technologies present many advantages to improve the quality of
      drug/gene/cell delivery systems. They also offer the benefits of automation. What
      remains unclear is whether they can meet the scale-up requirement. In this
      perspective, we discuss the advantages of microfluidic-assisted synthesis of
      nanoscale drug/gene delivery systems, formation of microscale drug/cell
      encapsulated particles, generation of genetically engineered cells and
      fabrication of macroscale drug/cell-loaded micro-/nano-fibers. We also highlight
      the scale-up challenges one would face in adopting microfluidic technologies for
      the manufacturing of these therapeutic delivery systems. 

PMID- 27047676
TI  - A pore way to heal and regenerate: 21st century thinking on biocompatibility.
AB  - This article raises central questions about the definition of biocompatibility,
      and also about how we assess biocompatibility. We start with the observation that
      a porous polymer where every pore is spherical, ~40 microns in diameter and
      interconnected, can heal into vascularized tissues with little or no fibrosis and
      good restoration of vascularity (i.e., little or no foreign body reaction). The
      same polymer in solid form will trigger the classic foreign body reaction
      characterized by a dense, collagenous foreign body capsule and low vascularity. A
      widely used definition of biocompatibility is 'the ability of a material to
      perform with an appropriate host response in a specific application'. With
      precision-porous polymers, in direct comparison with the same polymer in solid
      form, we have the same material, in the same application, with two entirely
      different biological reactions. Can both reactions be 'biocompatible?' This
      conundrum will be elaborated upon and proposals will be made for future
      considerations and measurement of biocompatibility. 

PMID- 27047675
TI  - Recent advances of biomaterials in biotherapy.
AB  - Biotherapy mainly refers to the intervention and the treatment of major diseases
      with biotechnologies or bio-drugs, which include gene therapy, immunotherapy
      (vaccines and antibodies), bone marrow transplantation and stem-cell therapy. In
      recent years, numerous biomaterials have emerged and were utilized in the field
      of biotherapy due to their biocompatibility and biodegradability. Generally,
      biomaterials can be classified into natural or synthetic polymers according to
      their source, both of which have attracted much attention. Notably, biomaterials
      based non-viral gene delivery vectors in gene therapy are undergoing rapid
      development with the emergence of surface-modified or functionalized materials.
      In immunotherapy, biomaterials appear to be attractive means for enhancing the
      delivery efficacy and the potency of vaccines. Additionally, hydrogels and
      scaffolds are ideal candidates in stem-cell therapy and tissue engineering. In
      this review, we present an introduction of biomaterials used in above biotherapy,
      including gene therapy, immunotherapy, stem-cell therapy and tissue engineering.
      We also highlighted the biomaterials which have already entered the clinical
      evaluation. 

PMID- 27047677
TI  - Expediting the transition from replacement medicine to tissue engineering.
AB  - In this article, an expansive interpretation of "Tissue Engineering" is proposed
      which is in congruence with classical and recent published definitions. I further
      simplify the definition of tissue engineering as: "Exerting systematic control of
      the body's cells, matrices and fluids." As a consequence, many medical therapies
      not commonly considered tissue engineering are placed in this category because of
      their effect on the body's responses. While the progress of tissue engineering
      strategies is inexorable and generally positive, it has been subject to setbacks
      as have many important medical therapies. Medical practice is currently
      undergoing a transition on several fronts (academics, start-up companies, going
      concerns) from the era of "replacement medicine" where body parts and functions
      are replaced by mechanical, electrical or chemical therapies to the era of tissue
      engineering where health is restored by regeneration generation or limitation of
      the body's tissues and functions by exploiting our expanding knowledge of the
      body's biological processes to produce natural, healthy outcomes. 

PMID- 27047679
TI  - The Quest toward limb regeneration: a regenerative engineering approach.
AB  - The Holy Grail to address the clinical grand challenge of human limb loss is to
      develop innovative strategies to regrow the amputated limb. The remarkable
      advances in the scientific understanding of regeneration, stem cell science,
      material science and engineering, physics and novel surgical approaches in the
      past few decades have provided a regenerative tool box to face this grand
      challenge and address the limitations of human wound healing. Here we discuss the
      convergence approach put forward by the field of Regenerative Engineering to use
      the regenerative tool box to design and develop novel translational strategies to
      limb regeneration. 

PMID- 27047678
TI  - Regeneration strategies after the adult mammalian central nervous system injury
      biomaterials.
AB  - The central nervous system (CNS) has very restricted intrinsic regeneration
      ability under the injury or disease condition. Innovative repair strategies,
      therefore, are urgently needed to facilitate tissue regeneration and functional
      recovery. The published tissue repair/regeneration strategies, such as cell
      and/or drug delivery, has been demonstrated to have some therapeutic effects on
      experimental animal models, but can hardly find clinical applications due to such
      methods as the extremely low survival rate of transplanted cells, difficulty in
      integrating with the host or restriction of blood-brain barriers to
      administration patterns. Using biomaterials can not only increase the survival
      rate of grafts and their integration with the host in the injured CNS area, but
      also sustainably deliver bioproducts to the local injured area, thus improving
      the microenvironment in that area. This review mainly introduces the advances of
      various strategies concerning facilitating CNS regeneration. 

PMID- 27047680
TI  - Grand challenge in Biomaterials-wound healing.
AB  - Providing improved health care for wound, burn and surgical patients is a major
      goal for enhancing patient well-being, in addition to reducing the high cost of
      current health care treatment. The introduction of new and novel biomaterials and
      biomedical devices is anticipated to have a profound effect on the future
      improvement of many deleterious health issues. This publication will discuss the
      development of novel non-stinging liquid adhesive bandages in healthcare
      applications developed by Rochal Industries. The scientists/engineers at Rochal
      have participated in commercializing products in the field of ophthalmology,
      including rigid gas permeable contact lenses, soft hydrogel contact lenses,
      silicone hydrogel contact lenses, contact lens care solutions and cleaners,
      intraocular lens materials, intraocular controlled drug delivery,
      topical/intraocular anesthesia, and in the field of wound care, as non-stinging,
      spray-on liquid bandages to protect skin from moisture and body fluids and
      medical adhesive-related skin injuries. Current areas of entrepreneurial activity
      at Rochal Industries pertain to the development of new classes of biomaterials
      for wound healing, primarily in regard to microbial infection, chronic wound
      care, burn injuries and surgical procedures, with emphasis on innovation in
      product creation, which include cell-compatible substrates/scaffolds for wound
      healing, antimicrobial materials for opportunistic pathogens and biofilm
      reduction, necrotic wound debridement, scar remediation, treatment of diabetic
      ulcers, amelioration of pressure ulcers, amelioration of neuropathic pain and
      adjuvants for skin tissue substitutes. 

PMID- 27047681
TI  - Opportunities and challenges for the development of polymer-based biomaterials
      and medical devices.
AB  - Biomaterials and medical devices are broadly used in the diagnosis, treatment,
      repair, replacement or enhancing functions of human tissues or organs. Although
      the living conditions of human beings have been steadily improved in most parts
      of the world, the incidence of major human's diseases is still rapidly growing
      mainly because of the growth and aging of population. The compound annual growth
      rate of biomaterials and medical devices is projected to maintain around 10% in
      the next 10 years; and the global market sale of biomaterials and medical devices
      is estimated to reach $400 billion in 2020. In particular, the annual consumption
      of polymeric biomaterials is tremendous, more than 8000 kilotons. The compound
      annual growth rate of polymeric biomaterials and medical devices will be up to 15
      30%. As a result, it is critical to address some widespread concerns that are
      associated with the biosafety of the polymer-based biomaterials and medical
      devices. Our group has been actively worked in this direction for the past two
      decades. In this review, some key research results will be highlighted. 

PMID- 27047682
TI  - The use of poly(styrene-block-isobutylene-block-styrene) as a microshunt to treat
      glaucoma.
AB  - The InnFocus MicroShunt(r) is a minimally invasive glaucoma drainage microtube
      used to shunt aqueous humor from the anterior chamber of the eye to a flap formed
      under the conjunctiva and Tenon's capsule. The safety and clinical performance of
      this device approaches that of trabeculectomy with mitomycin C, the current 'gold
      standard' treatment for advanced glaucoma. The invention of a new biomaterial
      called poly(styrene-block-isobutylene-block-styrene) or 'SIBS' is the enabling
      factor which led to the success of this product. SIBS is ultrastable with
      virtually no foreign body reaction in the body, which manifests as clinically
      insignificant inflammation and capsule formation in the eye. The lack of capsule
      formation enables unobstructed flow through the 70 um lumen tube and the
      achievement of controlled low intraocular pressure, which is important for the
      management of glaucoma. This article summarizes the integration of SIBS into a
      glaucoma drainage device and confirms its functionality with clinical success
      over a 2-year period. 

PMID- 27047683
TI  - Critical questions in development of targeted nanoparticle therapeutics.
AB  - One of the fourteen Grand Challenges for Engineering articulated by the US
      National Academy of Engineering is 'Engineer Better Medicines'. Although there
      are many ways that better medicines could be engineered, one of the most
      promising ideas is to improve our ability to deliver the therapeutic molecule
      more precisely to the desired target. Most conventional drug delivery methods
      (oral absorption, intravenous infusion etc.) result in systemic exposure to the
      therapeutic molecule, which places severe constraints on the types of molecules
      that can be used. A molecule administered by systemic delivery must be effective
      at low concentrations in the target tissue, yet safe everywhere else in the body.
      If drug carriers could be developed to deliver therapeutic molecules selectively
      to the desired target, it should be possible to greatly improve safety and
      efficacy of therapy. Nanoparticles (and related nanostructures, such as
      liposomes, nanoemulsions, micelles and dendrimers) are an attractive drug carrier
      concept because they can be made from a variety of materials engineered to have
      properties that allow loading and precise delivery of bound therapeutic
      molecules. The field of targeted nanoparticles has been extraordinarily active in
      the academic realm, with thousands of articles published over the last few years.
      Many of these publications seem to demonstrate very promising results in in vitro
      studies and even in animal models. In addition, a handful of human clinical
      trials are in progress. Yet, the biopharmaceutical industry has been relatively
      slow to make major investments in targeted nanoparticle development programs,
      despite a clear desire to introduce innovative new therapies to the market. What
      is the reason for such caution? Some degree of caution is no doubt due to the use
      of novel materials and the unproven nature of targeted nanoparticle technology,
      but many other unproven technologies have generated intense interest at various
      times. We believe that the major barrier to the exploration of nanoparticles is
      because they are so complex. The very design flexibility that makes the
      nanoparticle approach attractive also makes it challenging. Fortunately,
      continuing progress in experimental tools has greatly improved the ability to
      study biology and potential interventions at a nanoscale. Thus, it is
      increasingly possible to answer detailed questions about how nanoparticles can
      and should work. However, a detailed understanding at the mechanistic level is
      only the beginning. Any new medicine must not only work at the molecular level,
      but must also be manufactured reproducibly at scale and proven in the clinic. New
      materials will require new methods at all scales. The purpose of this short
      article is to focus on a set of questions that are being asked in the large
      biopharmaceutical companies and that must be answered if targeted nanoparticles
      are to become the medicines of the 21st century. 

PMID- 27047686
TI  - Viscoat Assisted Inverted Internal Limiting Membrane Flap Technique for Large
      Macular Holes Associated with High Myopia.
AB  - Purpose. To investigate the surgical outcomes of Viscoat(r) assisted inverted
      internal limiting membrane (ILM) flap technique for large macular holes (MHs)
      associated with high myopia. Design. Prospective, interventional case series.
      Methods. Fifteen eyes of 15 patients with high myopia underwent vitrectomy and
      Viscoat assisted inverted ILM flap technique to treat MH without RD. Patients
      were followed up over 6 months. The main outcome measures were MH closure
      evaluated by optical coherence tomography (OCT) and best-corrected visual
      acuities (BCVAs). Result. MH closure was observed in all eyes (100%) following
      the initial surgery. Type 1 closure was observed in 13 eyes (86.7%); type 2
      closure was observed in the remaining 2 eyes (13.3%). Compared to the
      preoperative baseline, the mean BCVA (logarithm of the minimum angle of
      resolution) improved significantly at 3 months and 6 months after surgery (P =
      0.025, 0.019, resp.). The final BCVA improved in 10 eyes (66.7%), remained
      unchanged in 3 eyes (20.0%), and worsened in 2 eyes (13.3%). Conclusion.
      Vitrectomy combined with Viscoat assisted inverted ILM flap technique is an
      effective treatment for large MHs in highly myopic eyes. It may increase the
      success rate of the initial surgery and enhance the anatomical and functional
      outcomes. 

PMID- 27047687
TI  - Effects of Lutein on Hyperosmoticity-Induced Upregulation of IL-6 in Cultured
      Corneal Epithelial Cells and Its Relevant Signal Pathways.
AB  - Dry eye is a common disorder characterized by deficiency of tear. Hyperosmoticity
      of tear stimulates inflammation and damage of ocular surface tissues and plays an
      essential role in the pathogenesis of dry eye. Cultured human corneal epithelial
      (CE) cells were used for the study of effects of lutein and hyperosmoticity on
      the secretion of IL-6 by CE cells. Cell viability of CE cells was not affected by
      lutein at 1-10 MUM as determined by MTT assay. Hyperosmoticity significantly
      elevated the secretion of IL-6 by CE cells as measured by ELISA analysis. The
      constitutive secretion of IL-6 was not affected by lutein. Lutein significantly
      and dose-dependently inhibited hyperosmoticity-induced secretion of IL-6.
      Phosphorylated- (p)- p38 MAPK, p-JNK levels in cell lysates and NF-kappaB levels
      in cell nuclear extracts were increased by being exposed to hyperosmotic medium.
      JNK, p38, and NF-kappaB inhibitors decreased hyperosmoticity-induced secretion of
      IL-6. Lutein significantly inhibited hyperosmoticity-induced elevation of NF
      kappaB, p38, and p-JNK levels. We demonstrated that lutein inhibited
      hyperosmoticity-induced secretion of IL-6 in CE cells through the deactivation of
      p38, JNK, and NF-kappaB pathways. Lutein may be a promising agent to be explored
      for the treatment of dry eye. 

PMID- 27047688
TI  - Evaluation of Olfactory and Gustatory Function of HIV Infected Women.
AB  - Background. Compliance with medication requires good sense of smell and taste.
      Objective. To evaluate the olfactory and gustatory function of HIV infected women
      in Ibadan, Nigeria. Methods. A case control study of women comprising 83 HIV
      infected women and 79 HIV uninfected women. Subjective self-rating of taste and
      smell function was by visual analogue scale. Olfactory function was measured via
      olfactory threshold (OT), olfactory discrimination (OD), olfactory identification
      (OI), and TDI using "Sniffin' sticks" kits and taste function (Total Taste Strips
      (TTS) score) measurement was by taste strips. Results. The mean age of the HIV
      infected women was 43.67 years +/- 10.72 and control was 41.48 years +/- 10.99.
      There was no significant difference in the self-reported assessment of smell (p =
      0.67) and taste (p = 0.84) of HIV infected and uninfected women. Although the
      mean OT, OD, OI, TDI, and TTS scores of HIV infected and uninfected women were
      within the normosmic and normogeusic values, the values were significantly higher
      in the controls (p < 0.05). Hyposmia was in 39.7% of subjects and 12.6% of
      controls while hypogeusia was in 15.7% of subjects and 1.3% of controls.
      Conclusions. Hyposmia and hypogeusia are commoner among the HIV infected women
      than the HIV uninfected women and the risk increases with an increased duration
      of highly active antiretroviral therapy. 

PMID- 27047689
TI  - General Practitioners' Participation in a Large, Multicountry Combined General
      Practitioner-Patient Survey: Recruitment Procedures and Participation Rate.
AB  - Background. The participation of general practitioners (GPs) is essential in
      research on the performance of primary care. This paper describes the
      implementation of a large, multicountry study in primary care that combines a
      survey among GPs and a linked survey among patients that visited their practice
      (the QUALICOPC study). The aim is to describe the recruitment procedure and
      explore differences between countries in the participation rate of the GPs.
      Methods. Descriptive analyses were used to document recruitment procedures and to
      assess hypotheses potentially explaining variation in participation rates between
      countries. Results. The survey was implemented in 31 European countries. GPs were
      mainly selected through random sampling. The actual implementation of the study
      differed between countries. The median participation rate was 30%. Both material
      (such as the payment system of GPs in a country) and immaterial influences (such
      as estimated survey pressure) are related to differences between countries.
      Conclusion. This study shows that the participation of GPs may indeed be
      influenced by the context of the country. The implementation of complex data
      collection is difficult to realize in a completely uniform way. Procedures have
      to be tuned to the context of the country. 

PMID- 27047690
TI  - Anatomical Considerations on Surgical Anatomy of the Carotid Bifurcation.
AB  - Surgical anatomy of carotid bifurcation is of unique importance for numerous
      medical specialties. Despite extensive research, many aspects such as precise
      height of carotid bifurcation, micrometric values of carotid arteries and their
      branches as their diameter, length, and degree of tortuosity, and variations of
      proximal external carotid artery branches are undetermined. Furthermore carotid
      bifurcation is involved in many pathologic processes, atheromatous disease being
      the commonest. Carotid atheromatous disease is a major predisposing factor for
      disabling and possibly fatal strokes with geometry of carotid bifurcation playing
      an important role in its natural history. Consequently detailed knowledge of
      various anatomic parameters is of paramount importance not only for understanding
      of the disease but also for design of surgical treatment, especially selection
      between carotid endarterectomy and carotid stenting. Carotid bifurcation
      paragangliomas constitute unique tumors with diagnostic accuracy, treatment
      design, and success of operative intervention dependent on precise knowledge of
      anatomy. Considering those, it becomes clear that selection and application of
      proper surgical therapy should consider anatomical details. Further research
      might ameliorate available treatment options or even lead to innovative ones. 

PMID- 27047691
TI  - Serotyping and Antimicrobial Susceptibility Pattern of Escherichia coli Isolates
      from Urinary Tract Infections in Pediatric Population in a Tertiary Care
      Hospital.
AB  - Urinary tract infections (UTIs) in pediatric population are associated with high
      morbidity and long term complications. In recent years, there is increased
      prevalence of Escherichia coli (E. coli) strains producing extended spectrum beta
      lactamase, Amp C, and Metallo beta-lactamase, making the clinical management even
      more difficult. This study was aimed to detect the serotypes and to determine
      antimicrobial susceptibility profile of E. coli isolates from urine samples of
      children <10 yrs old. A total of 75 pure E. coli strains isolated from patients
      with symptoms of UTI and colony count >=10(5) organisms/mL were included in the
      study. Antibiotic sensitivity pattern showed maximum resistance to nalidixic acid
      (98.7%), followed by ampicillin (97.3%), amoxi-clavulanate (96%), and
      fluoroquinolones (92%) while most of the isolates were found sensitive to
      piperacillin-tazobactam (13.3%), nitrofurantoin (5.3%), and meropenem (1.3%). 48%
      of the strains were ESBL producer (extended spectrum beta lactamase). 44% strains
      were typable withantisera used in our study and the most common serogroup was O6
      (33.3%) followed by O1 (15.1%) and O15 (15.1%). To conclude, judicious use of
      antibiotics according to hospital antibiotic policy and infection control
      measures should be implemented to prevent spread of multidrug resistant
      organisms. 

PMID- 27047692
TI  - Antibiotic Prophylaxis for Gynecologic Procedures prior to and during the
      Utilization of Assisted Reproductive Technologies: A Systematic Review.
AB  - The use of assisted reproductive technologies (ART) has increased steadily. There
      has been a corresponding increase in the number of ART-related procedures such as
      hysterosalpingography (HSG), saline infusion sonography (SIS), hysteroscopy,
      laparoscopy, oocyte retrieval, and embryo transfer (ET). While performing these
      procedures, the abdomen, upper vagina, and endocervix are breached, leading to
      the possibility of seeding pelvic structures with microorganisms. Antibiotic
      prophylaxis is therefore important to prevent or treat any procedure-related
      infections. After careful review of the published literature, it is evident that
      routine antibiotic prophylaxis is generally not recommended for the majority of
      ART-related procedures. For transcervical procedures such as HSG, SIS,
      hysteroscopy, ET, and chromotubation, patients at risk for pelvic infections
      should be screened and treated prior to the procedure. Patients with a history of
      pelvic inflammatory disease (PID) or dilated fallopian tubes are at high risk for
      postprocedural infections and should be given antibiotic prophylaxis during
      procedures such as HSG, SIS, or chromotubation. Antibiotic prophylaxis is
      recommended prior to oocyte retrieval in patients with a history of
      endometriosis, PID, ruptured appendicitis, or multiple prior pelvic surgeries. 

PMID- 27047693
TI  - Vancomycin and High Level Aminoglycoside Resistance in Enterococcus spp. in a
      Tertiary Health Care Centre: A Therapeutic Concern.
AB  - Aims. This study was aimed at knowing the prevalence of vancomycin and high level
      aminoglycoside resistance in enterococcal strains among clinical samples. Study
      Design. It was an investigational study. Place and Duration of Study. It was
      conducted on 100 Enterococcus isolates, in the Department of Microbiology, Pt.
      BDS PGIMS, Rohtak, over a period of six months from July to December 2014.
      Methodology. Clinical specimens including urine, pus, blood, semen, vaginal swab,
      and throat swab were processed and Enterococcus isolates were identified by
      standard protocols. Antibiotic sensitivity testing of enterococci was performed
      using Kirby-Bauer disc diffusion method. Results. High level gentamicin
      resistance (HLGR) was more common in urine samples (41.5%) followed by blood
      (36%) samples. High level streptomycin resistance (HLSR) was more common in pus
      samples (52.6%) followed by blood samples (36%). Resistance to vancomycin was
      maximum in blood isolates. Conclusion. Enterococci resistant to multiple
      antimicrobial agents have been recognized. Thus, it is crucial for laboratories
      to provide accurate antimicrobial resistance patterns for enterococci so that
      effective therapy and infection control measures can be initiated. 

PMID- 27047694
TI  - Manipulation of Dysfunctional Spinal Joints Affects Sensorimotor Integration in
      the Prefrontal Cortex: A Brain Source Localization Study.
AB  - Objectives. Studies have shown decreases in N30 somatosensory evoked potential
      (SEP) peak amplitudes following spinal manipulation (SM) of dysfunctional
      segments in subclinical pain (SCP) populations. This study sought to verify these
      findings and to investigate underlying brain sources that may be responsible for
      such changes. Methods. Nineteen SCP volunteers attended two experimental
      sessions, SM and control in random order. SEPs from 62-channel EEG cap were
      recorded following median nerve stimulation (1000 stimuli at 2.3 Hz) before and
      after either intervention. Peak-to-peak amplitude and latency analysis was
      completed for different SEPs peak. Dipolar models of underlying brain sources
      were built by using the brain electrical source analysis. Two-way repeated
      measures ANOVA was used to assessed differences in N30 amplitudes, dipole
      locations, and dipole strengths. Results. SM decreased the N30 amplitude by 16.9
      +/- 31.3% (P = 0.02), while no differences were seen following the control
      intervention (P = 0.4). Brain source modeling revealed a 4-source model but only
      the prefrontal source showed reduced activity by 20.2 +/- 12.2% (P = 0.03)
      following SM. Conclusion. A single session of spinal manipulation of
      dysfunctional segments in subclinical pain patients alters somatosensory
      processing at the cortical level, particularly within the prefrontal cortex. 

PMID- 27047696
TI  - Left Main Coronary Artery Hypoplasia in Elderly.
AB  - Congenital anomalies of the coronary artery causing coronary occlusive disease
      may be of many different types. A 67-year-old woman with no coronary risk factors
      was referred for coronary angiography with few months' history of angina. The
      patient underwent coronary angiography due to ischemic cardiac symptoms with
      nondiagnostic exercising test. In coronary angiography, the left main coronary
      artery was arising from normal anatomical position; however, left anterior
      descending artery and circumflex artery were hypoplastic. The treatment of
      patient was discussed in cardiology-cardiovascular surgery council and coronary
      surgery was found inappropriate due to the hypoplasia of the left coronary system
      entirely. 

PMID- 27047697
TI  - Inflammatory Breast Cancer from Metastatic Ovarian Cancer.
AB  - Metastases to the breast from tumors other than breast carcinomas are extremely
      rare and represent only 0.2-1.3% of all diagnosed malignant breast tumors.
      Furthermore, while the most common sites for advanced ovarian cancer metastases
      are the liver, lung, and pleura, metastasis to the breast from a primary ovarian
      cancer is uncommon and has only been reported in 0.03-0.6% of all breast cancers.
      Here we describe a case report of a 50-year-old female patient with a rare case
      of breast metastases from an advanced ovarian cancer, presenting as inflammatory
      breast cancer. Our observations emphasize the clinical importance of
      distinguishing between primary and metastatic breast cancer during diagnosis for
      the purpose of appropriate prognosis and treatment. 

PMID- 27047695
TI  - Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury.
AB  - Hypoxic-ischaemic damage to the developing brain is a leading cause of child
      death, with high mortality and morbidity, including cerebral palsy, epilepsy, and
      cognitive disabilities. The developmental stage of the brain and the severity of
      the insult influence the selective regional vulnerability and the subsequent
      clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI)
      of periventricular white matter in preterm infants predisposes the immature brain
      to motor, cognitive, and sensory deficits, with cognitive impairment associated
      with earlier gestational age. In term infants HI causes selective damage to
      sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the
      immature brain is more malleable to external stimuli compared to the adult one, a
      hypoxic-ischaemic event to the neonate interrupts the shaping of central motor
      pathways and can affect normal developmental plasticity through altering
      neurotransmission, changes in cellular signalling, neural connectivity and
      function, wrong targeted innervation, and interruption of developmental
      apoptosis. Models of neonatal HI demonstrate three morphologically different
      types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk
      and can exist as a continuum in the same cell. In the present review we discuss
      the mechanisms of HI injury to the immature brain and the way they affect
      plasticity. 

PMID- 27047698
TI  - Combined Endoscopic and Laparoscopic Management of Postcholecystectomy Mirizzi
      Syndrome from a Remnant Cystic Duct Stone: Case Report and Review of the
      Literature.
AB  - Mirizzi syndrome has been defined in the literature as common bile duct
      obstruction resulting from calculi within Hartmann's pouch or cystic duct. We
      present a case of a 78-year-old female, who developed postcholecystectomy Mirizzi
      syndrome from a remnant cystic duct stone. Diagnosis of postcholecystectomy
      Mirizzi syndrome was made on endoscopic retrograde cholangiography (ERCP)
      performed postoperatively. The patient was treated with a novel strategy by
      combining advanced endoscopic and laparoscopic techniques in three stages as
      follows: Stage 1 (initial presentation): endoscopic sphincterotomy with common
      bile duct stent placement; Stage 2 (6 weeks after Stage 1): laparoscopic
      ultrasonography to locate the remnant cystic duct calculi followed by
      laparoscopic retrieval of the calculi and intracorporeal closure of cystic duct
      stump; Stage 3 (6 weeks after Stage 2): endoscopic removal of common bile duct
      stent along with performance of completion endoscopic retrograde cholangiogram.
      In addition, we have performed an extensive review of the various endoscopic and
      laparoscopic management techniques described in the literature for the treatment
      of postcholecystectomy syndrome occurring from retained cystic duct stones. 

PMID- 27047699
TI  - Correlation between Doppler, Manual Morphometry, and Histopathology Based
      Morphometry of Radial Artery as a Conduit in Coronary Artery Bypass Grafting.
AB  - Background. Long-term graft patency is the major factor impacting survival after
      coronary artery bypass grafting. Arteries are superior in this regard. Radial
      artery is considered the second best conduit after internal mammary artery.
      Several studies have shown excellent radial artery patency. We evaluated the
      morphologic characteristics of radial artery by three modalities, (i)
      preoperative Doppler ultrasound, (ii) intraoperative manual morphometry, and
      (iii) postoperative histology-based morphometry, and compared these with the aim
      of validating Doppler as a noninvasive test of choice for preoperative assessment
      of radial artery. Methods. This was a prospective study involving 100 patients
      undergoing coronary artery bypass grafting in which radial artery was used. The
      radial artery was assessed using preoperative Doppler ultrasound studies,
      intraoperative morphometry, and postoperative histopathology and morphometry. The
      morphometric measurements included (i) luminal diameter, (ii) intimal and medial
      thickness, and (iii) intima-media thickness ratio. Results. Using Bland-Altman
      plots, there was a 95% limit of agreement between the preoperative Doppler
      measurements and the postoperative histopathology and morphometry. Conclusion.
      Doppler ultrasound is an accurate screening test for evaluation of radial artery,
      in terms of intimal/medial thickness and luminal diameter as a conduit in
      coronary artery bypass grafting and has been validated by both morphometric and
      histopathology based studies. 

PMID- 27047700
TI  - Bone Strength and Arterial Stiffness Impact on Cardiovascular Mortality in a
      General Population.
AB  - Osteoporosis and increased arterial stiffness independently have been found to be
      associated with higher cardiovascular events rates in the general population
      (GP). We examined 558 patients from GP by dual-energy X-ray absorptiometry (DXA)
      and pulse wave velocity (PWV) measurements at baseline, with 36-month follow-up
      period. DXA assessed bone mineral density of femoral neck (BMD FN) and lumbar
      spine (BMD LS). Carotid-femoral PWV was assessed by pulsed-Doppler. The aim of
      our study is to find correlation between bone strength and arterial stiffness and
      their impact on cardiovascular mortality in GP. The mean +/- SD of BMD FN, BMD
      LS, and PWV was 0.852 +/- 0.1432 g/cm(2), 0.934 +/- 0.1546 g/cm(2), and 9.209 +/-
      1.9815 m/s. In multiple regression analysis we found BMD FN (betast = -6.0094, p
      < 0.0001), hypertension (betast = 1.7340, p < 0.0091), and diabetes (betast =
      0.4595, p < 0.0046). With Cox-regression analysis, after 17 cardiovascular
      events, the significant covariates retained by the backward model were BMD FN (b
      = -2.4129, p = 0.015) and PWV (b = 0.2606, p = 0.0318). The cut-off values were
      PWV = 9.4 m/s, BMD FN = 0.783 g/cm(2), and BMD LS = 0.992 g/cm(2). The results
      for BMD FN and PWV hazard ratio risk were 1.116 and 1.297, respectively. BMD FN
      as a measure of bone strength and PWV as a measure of arterial stiffness are
      strong independent predictors of cardiovascular mortality in GP. 

PMID- 27047701
TI  - Severe Malaria Associated with Plasmodium falciparum and P. vivax among Children
      in Pawe Hospital, Northwest Ethiopia.
AB  - Despite rigorous effort made to control malaria for more than a century, it is
      still among the main public health problems in least developed regions of the
      world. Majority of deaths associated with malaria occur in sub-Sahara Africa
      among biologically risked groups. Thus, this study was designed to assess the
      incidence of severe malaria syndromes among children in Pawe Hospital, Northwest
      Ethiopia. Children seeking medication for malaria infection in Pawe Hospital
      during the study period were recruited. Sociodemographic characteristics,
      physical, hematological, and clinical features of complicated malaria were
      assessed following standard parasitological and clinical procedures. A total of
      263 children were found malaria positive. Among these, 200 were infected with
      Plasmodium falciparum. Most of the severe malaria symptoms were observed among
      children infected with P. falciparum and P. vivax. The study showed that
      significant number of the children developed severe life threatening malaria
      complications. This calls for prompt early diagnosis and effective treatment of
      patients to reduce mortality and complications associated with malaria in the
      study site. 

PMID- 27047702
TI  - A pan-cancer analysis of prognostic genes.
AB  - Numerous studies have identified prognostic genes in individual cancers, but a
      thorough pan-cancer analysis has not been performed. In addition, previous
      studies have mostly used microarray data instead of RNA-SEQ, and have not
      published comprehensive lists of associations with survival. Using recently
      available RNA-SEQ and clinical data from The Cancer Genome Atlas for 6,495
      patients, we have investigated every annotated and expressed gene's association
      with survival across 16 cancer types. The most statistically significant harmful
      and protective genes were not shared across cancers, but were enriched in
      distinct gene sets which were shared across certain groups of cancers. These
      groups of cancers were independently recapitulated by both unsupervised
      clustering of Cox coefficients (a measure of association with survival) for
      individual genes, and for gene programs. This analysis has revealed unappreciated
      commonalities among cancers which may provide insights into cancer pathogenesis
      and rationales for co-opting treatments between cancers. 

PMID- 27047703
TI  - Contrasting response of biomass and grain yield to severe drought in Cappelle
      Desprez and Plainsman V wheat cultivars.
AB  - We report a case study of natural variations and correlations of some
      photosynthetic parameters, green biomass and grain yield in Cappelle Desprez and
      Plainsman V winter wheat (Triticum aestivum L.) cultivars, which are classified
      as being drought sensitive and tolerant, respectively. We monitored biomass
      accumulation from secondary leaves in the vegetative phase and grain yield from
      flag leaves in the grain filling period. Interestingly, we observed higher
      biomass production, but lower grain yield stability in the sensitive Cappelle
      cultivar, as compared to the tolerant Plainsman cv. Higher biomass production in
      the sensitive variety was correlated with enhanced water-use efficiency.
      Increased cyclic electron flow around PSI was also observed in the Cappelle cv.
      under drought stress as shown by light intensity dependence of the ratio of
      maximal quantum yields of Photosystem I and Photosystem II, as well by the plot
      of the Photosystem I electron transport rate as a function of Photosystem II
      electron transport rate. Higher CO2 uptake rate in flag leaves of the drought
      stressed Plainsman cv. during grain filling period correlates well with its
      higher grain yield and prolonged transpiration rate through spikes. The increase
      in drought factor (DFI) and performance (PI) indices calculated from variable
      chlorophyll fluorescence parameters of secondary leaves also showed correlation
      with higher biomass in the Cappelle cultivar during the biomass accumulation
      period. However, during the grain filling period, DFI and PI parameters of the
      flag leaves were higher in the tolerant Plainsman V cultivar and showed
      correlation with grain yield stability. Our results suggest that overall biomass
      and grain yield may respond differentially to drought stress in different wheat
      cultivars and therefore phenotyping for green biomass cannot be used as a general
      approach to predict grain yield. We also conclude that photosynthetic efficiency
      of flag and secondary leaves is correlated with grain yield and green biomass,
      respectively. In addition, secondary trait associated mechanisms like delayed
      senescence and higher water-use efficiency also contribute to biomass stability.
      Our studies further prove that photosynthetic parameters could be used to
      characterize environmental stress responses. 

PMID- 27047704
TI  - Factor structure of the Positive and Negative Affect Schedule (PANAS) in adult
      women with fibromyalgia from Southern Spain: the al-Andalus project.
AB  - BACKGROUND: Fibromyalgia is a syndrome characterized by the presence of
      widespread chronic pain. People with fibromyalgia report lower levels of Positive
      Affect and higher levels of Negative Affect than non-fibromyalgia peers. The
      Positive and Negative Affect Schedule (PANAS)-a widely used questionnaire to
      assess two core domains of affect; namely 'Positive Affect' and 'Negative Affect'
      -has a controversial factor structure varying across studies. The internal
      structure of a measurement instrument has an impact on the meaning and validity
      of its score. Therefore, the aim of the present study was to assess the
      structural construct validity of the PANAS in adult women with fibromyalgia.
      METHODS: This population-based cross-sectional study included 442 adult women
      with fibromyalgia (age: 51.3 +/- 7.4 years old) from Andalusia (Southern Spain).
      Confirmatory factor analyses were conducted to test the factor structure of the
      PANAS. RESULTS: A structure with two correlated factors (Positive Affect and
      Negative Affect) obtained the best fit; S-B chi(2) = 288.49, df = 155, p < .001;
      RMSEA = .04; 90% CI of RMSEA = (.036, .052); the best fit SRMR = .05; CFI = .96;
      CAIC = -810.66, respectively. CONCLUSIONS: The present study demonstrates that
      both Positive Affect and Negative Affect are core dimensions of affect in adult
      women with fibromyalgia. A structure with two correlated factors of the PANAS
      emerged from our sample of women with fibromyalgia from Andalusia (Southern
      Spain). In this model, the amount of variance shared by Positive Affect and
      Negative Affect was small. Therefore, our findings support to use and interpret
      the Positive Affect and Negative Affect subscales of the PANAS as separate
      factors that are associated but distinctive as well.

PMID- 27047705
TI  - Characterization of Japanese cedar bio-oil produced using a bench-scale auger
      pyrolyzer.
AB  - A bench-scale auger reactor was designed for use as a laboratory-scale fast
      pyrolyzer for producing bio-oil from Japanese cedar. An analytical pyrolysis
      method was performed simultaneously to determine the distribution of pyrolysis
      products. The pyrolysis temperature was found to have the greatest influence on
      the bio-oil characteristics; bio-oil yields increased as the pyrolysis
      temperature increased from 450 to 550  degrees C. The concentration of
      levoglucosan in the bio-oil, however, decreased significantly with increasing
      pyrolysis temperature, while it increased following analytical pyrolysis. The
      same results were obtained for 4-vinylguaiacol and E-isoeugenol, which were the
      major secondary products produced in the present study. Compared to the yields of
      these major products obtained via analytical pyrolysis, the yields from the auger
      reactor were very low, indicating that the auger reactor process had a longer
      vapor residence time than the analytical pyrolysis process, resulting in the
      acceleration of secondary reactions of the pyrolysates. The pH values and
      densities of the bio-oils produced in the auger reactor were similar to those
      reported by researchers using woody biomass, despite their lower viscosities.
      From these results, it was concluded that the pyrolysis temperature and residence
      time of the pyrolysates played a significant role in determining the
      characteristics of the cedar bio-oil. 

PMID- 27047706
TI  - Space maintenance in autogenous fresh demineralized tooth blocks with platelet
      rich plasma for maxillary sinus bone formation: a prospective study.
AB  - This prospective study evaluated the effectiveness of autogenous fresh
      demineralized tooth block (Auto-FDT block) with platelet-rich plasma (PRP) for
      maxillary sinus augmentation with simultaneous implant installation. Auto-FDT
      block with PRP was used in Group 1 (n = 15) and combined graft (allograft and
      xenograft) powder with PRP was used in Group 2 (n = 15). For up to 2 years after
      the final prosthesis was installed, clinical and radiographic examinations were
      performed to evaluate the amount of graft materials, residual alveolar height
      (RAH), sinus height (SH) after grafting, augmented graft height (AGH) and
      resorption height (RH). In ten cases, biopsies were harvested for histological
      and histomorphometric analyses. A total of 59 implants were placed in a severe
      atrophic posterior maxilla with less than 5 mm of RAH and sinus augmentation.
      None of the patients developed sinusitis or other complications, such as implant
      loss. The graft material extracted included one molar (or 2 premolars) in Group 1
      and 1.8 cc in Group 2. The radiologic examination revealed the following average
      between-group difference SH (Group 1, 14.12 +/- 1.63 mm vs Group 2, 16.51 +/-
      1.29 mm) and AGH (Group 1, 11.62 +/- 2.22 mm vs Group 2, 13.65 +/- 1.35 mm).
      However, sufficient SH and AGH were observed for the implants in the Auto-FDT
      block group. Two years after final prosthesis was installed, no between-group
      difference in the RH was observed (Group 1, 1.23 +/- 0.73 mm vs Group 2, 1.77 +/-
      0.54 mm, P = 0.021). The histomorphometric analysis revealed no between-group
      difference in the new bone volume (Group 1, 23.13 +/- 1.42 % vs Group 2, 24.18 +/
      2.19 %, P = 0.548). The results showed that Auto-FDT block with PRP can be used
      in grafted sinuses for implants with only one extracted molar (or two premolars).
      Auto-FDT block with PRP promotes new bone formation that is comparable with
      combined grafts. Auto-FDT block with PRP is as an alternative to bone grafting
      and can be a predictable procedure for sinus augmentation. 

PMID- 27047707
TI  - An efficient technique for higher order fractional differential equation.
AB  - In this study, we establish exact solutions of fractional Kawahara equation by
      using the idea of [Formula: see text]-expansion method. The results of different
      studies show that the method is very effective and can be used as an alternative
      for finding exact solutions of nonlinear evolution equations (NLEEs) in
      mathematical physics. The solitary wave solutions are expressed by the
      hyperbolic, trigonometric, exponential and rational functions. Graphical
      representations along with the numerical data reinforce the efficacy of the used
      procedure. The specified idea is very effective, expedient for fractional PDEs,
      and could be extended to other physical problems. 

PMID- 27047708
TI  - Devolution and grant-in-aid design for the provision of impure public goods.
AB  - Traditional fiscal federalism theory postulates that devolution for the provision
      of local public goods increases welfare. However, most of the services offered at
      local level are local impure public goods whose characteristics may prevent
      devolution from being efficient. Our paper shows that devolution is the optimal
      choice only for local impure public goods. For an environment characterised by
      coordination and asymmetry of information problems, we propose the optimal grants
      in-aid formula that Central Government should use to reduce welfare losses and we
      compare it with what suggested by the mainstream literature. Finally, we show
      under which conditions devolution should be preferred to a centralised solution.
      From a policy point of view, our paper may explain the heterogeneity in the
      choices made by countries in terms of devolution in the provision of merit and
      impure public goods. 

PMID- 27047709
TI  - Characterisation of soils under long-term crop cultivation without fertilisers: a
      case study in Japan.
AB  - Certain farms in Japan, namely unfertilised farms (UFs), have been able to
      maintain high productivity for over 40 years without applying fertilisers or
      composts. This study aimed to characterise the physicochemical, biological and
      micromorphological properties of soil in UFs compared with control farms in Eniwa
      and Nariita and to identify characteristics that are associated with crop
      productivity. In UFs, no plough pan was observed. The thickness of the effective
      soil depth (ESD) of UFs was greater than that of CFs. The concentrations of soil
      organic carbon, total nitrogen and nitrate-nitrogen in ESD of UFs were higher
      than those in ESD of CFs. Soil microstructure observations indicated the strong
      development of a granular microstructure with large amounts of void space and a
      high fractal dimension in both surface and subsoil horizons of UFs. Dry yield had
      a strong correlation with ESD thickness and fractal dimension of voids. Thus, the
      management of unfertilised cultivation promoted the development of soil
      aggregation in both A and B horizons. The increase in ESD, soil pore spaces and
      complexity with the development of subsoil structure improved the productivity of
      unfertilised cultivation. 

PMID- 27047710
TI  - Some results on T-stability of Picard's iteration.
AB  - We prove the existence and uniqueness of fixed points of T-stability for an
      iteration on partial cone metric space of Zamfirescu contraction. As an
      application, we prove a theorem for integral equation. We also give illustrative
      examples to verify our results. 

PMID- 27047711
TI  - A putative HIV-1 subtype C/CRF11_cpx unique recombinant from South Africa.
AB  - The HIV epidemic in South Africa is overwhelmingly driven by HIV-1 subtype C
      viruses. The HIV gag, pol, env (C2-V5) and nef sequences of virus 08MB26ZA,
      obtained from a 47 year old woman, were studied by phylogenetic analysis, REGA
      and the jumping Profile Hidden Markov Model (jPHMM) tools. The pol gene was
      further analyzed for recombination by Simplot. The pol and env sequences were
      examined for genetic drug resistance mutations and predicted co-receptor usage
      respectively. There was agreement in the assignment of the gag sequence as pure
      HIV-1 subtype C by phylogenetic, REGA and jPHMM analyses. The pol sequence
      clustered with CRF11_cpx and in the J-clade by phylogenetic analysis; and to a
      CRF11_cpx/subtype C recombinant by REGA. The assignment of pol to CRF11_cpx and
      subtype C was confirmed by Simplot. The recombinant was of the R5 biotype, with
      no important drug resistance mutations in the pol region. The epidemiologic and
      biologic significance of the virus are unknown. The finding suggests that complex
      viruses are being introduced into South Africa with potential implications for
      diagnosis. This is apparently the first report from South Africa of a putative
      unique recombinant involving CRF11_cpx and subtype C genomes. 

PMID- 27047712
TI  - Level of habitual physical activity in children and adolescents from the Region
      of Murcia (Spain).
AB  - The level of physical activity of people is a very important issue
      internationally. The aim of this study was to analyze the level of habitual
      physical activity in children and adolescents from the Region of Murcia (Spain).
      With this purpose, the questionnaire Physician-based Assessment and Counseling
      for Exercise (PACE) was administered to 1055 children and adolescents (532 males
      and 523 females), aged between 3 and 18 years. The results showed that the sample
      studied does not do enough physical activity, according to the recommendations of
      the World Health Organization, as they do at least 60 min of physical activity
      only an average of 3.29 days/week (SD = 1.84). Besides, 77 % of the
      schoolchildren studied is inactive according to the classification of PACE
      questionnaire. According to sex, there are more active boys (31.2 %) than active
      girls (14.9 %) and, on average, boys do more physical activity than girls, almost
      a day more per week. 

PMID- 27047713
TI  - Homotopy perturbation method: a versatile tool to evaluate linear and nonlinear
      fuzzy Volterra integral equations of the second kind.
AB  - In this article, we focus on linear and nonlinear fuzzy Volterra integral
      equations of the second kind and we propose a numerical scheme using homotopy
      perturbation method (HPM) to obtain fuzzy approximate solutions to them. To
      facilitate the benefits of this proposal, an algorithmic form of the HPM is also
      designed to handle the same. In order to illustrate the potentiality of the
      approach, two test problems are offered and the obtained numerical results are
      compared with the existing exact solutions and are depicted in terms of plots to
      reveal its precision and reliability. 

PMID- 27047714
TI  - The topology of the directed clique complex as a network invariant.
AB  - We introduce new algebro-topological invariants of directed networks, based on
      the topological construction of the directed clique complex. The shape of the
      underlying directed graph is encoded in a way that can be studied mathematically
      to obtain network invariants such as the Euler characteristic and the Betti
      numbers. Two different cases illustrate the application of the Euler
      characteristic. We investigate how the evolution of a Boolean recurrent
      artificial neural network is influenced by its topology in a dynamics involving
      pruning and strengthening of the connections, and to show that the topological
      features of the directed clique complex influence the dynamical evolution of the
      network. The second application considers the directed clique complex in a
      broader framework, to define an invariant of directed networks, the network
      degree invariant, which is constructed by computing the topological invariant on
      a sequence of sub-networks filtered by the minimum in- or out-degree of the
      nodes. The application of the Euler characteristic presented here can be extended
      to any directed network and provides a new method for the assessment of specific
      functional features associated with the network topology. 

PMID- 27047715
TI  - Effect of lycopene on the copper-induced oxidation of low-density lipoprotein in
      broiler chickens.
AB  - The present study was undertaken to investigate whether dietary lycopene (LP)
      could prevent the copper-mediated oxidation of low density lipoprotein (LDL), and
      affect growth performance, relative organ weights, plasma and meat lipid
      profiles, and LP contents in plasma and tissues in broiler chickens. A total of
      160 day-old male broiler chicks were randomly allotted into 16 pens with rice
      husk as a bedding material. Each experiment had 4 replicates, 10 chicks per
      replicate (n = 4 per treatment). A corn-soybean meal base diet was used as a
      control diet (CONT). To formulate the experimental diets, the base diet was added
      with LP at the levels of 10 (LP10) or 20 mg/kg (LP20), or 17 g/kg of tomato paste
      (TP17) which was equivalent to 5 ppm of LP. The experiment lasted 4 weeks. Growth
      performance and relative organ weights were not affected (p > 0.05) by any of
      dietary treatments. Dietary LP significantly lowered (p < 0.05) triglyceride and
      LDL cholesterol at 2 weeks of age, but did not affect them at 4 weeks of age.
      Total cholesterol in thigh meats was not altered by dietary treatments. LP was
      not detected in leg meats in all chicks, nor in liver or plasma of the CONT
      group. LP was found in liver and plasma, being the former greater in the
      concentration, of the chicks fed diets containing LP10, LP20, or TP17. At 2 and 4
      weeks, the copper-mediated oxidation of LDL was delayed (p < 0.05) in either LP-
      or TP-fed chickens compared with the CONT group. In conclusion, LP lowers
      triglyceride and LDL cholesterol, is deposited into serum and liver, and prevents
      the LDL oxidation in broiler chickens, confirming the role of LP in the lipid
      lowering and antioxidant properties in broiler chickens. 

PMID- 27047717
TI  - A performance comparison of static VAr compensator based on Goertzel and FFT
      algorithm and experimental validation.
AB  - The main objective of the present paper is to introduce a new approach for
      measuring and calculation of fundamental power components in the case of various
      distorted waveforms including those containing harmonics. The parameters of
      active, reactive, apparent power and power factor, are measured and calculated by
      using Goertzel algorithm instead of fast Fourier transformation which is commonly
      used. The main advantage of utilizing Goertzel algorithm is to minimize
      computational load and trigonometric equations. The parameters measured in the
      new technique are applied to a fixed capacitor-thyristor controlled reactor based
      static VAr compensation system to achieve accurate power factor correction for
      the first time. This study is implemented both simulation and experimentally. 

PMID- 27047716
TI  - A feasibility study exploring the role of pre-operative assessment when examining
      the mechanism of 'chemo-brain' in breast cancer patients.
AB  - BACKGROUND: Women receiving chemotherapy treatment for breast cancer may
      experience problems with their memory and attention (cognition), which is
      distressing and interferes with quality of life. It is unclear what causes or
      contributes to the problems they report: psychological distress, fatigue, coping
      style, or specific biological changes for example to pro inflammatory cytokines.
      Research shows however, that approximately a third of women with breast cancer
      perform poorly on tests of cognition before commencing chemotherapy. We aimed to
      examine the acceptability and relevance of pre-surgical assessments (bloods,
      brain imaging, cognitive tests and self-report questionnaires) when investigating
      the phenomenon of 'chemo-brain' and investigate whether inflammatory markers
      mediate chemotherapy-induced neuropsychological impairments in women treated for
      breast cancer. METHODS: Women with early stage breast cancer completed
      neuropsychological and quality of life assessments at T1 (pre-surgery), T2 (post
      surgery before chemotherapy) and T3 (6 months later). Blood cytokine levels were
      measured at the same time points and brain imaging was performed at T1 and T3.
      RESULTS: In total, 14/58 women participated (8 chemotherapy, 6 non-chemotherapy).
      Prior to the start of chemotherapy a decline in cognitive performance compared to
      baseline was observed in one participant. At T3 women who received chemotherapy
      reported poorer quality of life and greater fatigue. Increases in soluble tumour
      necrosis factor receptor II (sTNFRII), interleukin-6, interleukin-10 and vascular
      endothelial growth factor occurred post chemotherapy only. Levels of sTNFRII were
      inversely correlated with grey matter volume (GMV) of the right posterior insula
      in both groups. At T3, the chemotherapy group displayed a greater reduction in
      GMV in the subgenual and dorsal anterior cingulate, and the inferior temporal
      gyrus. CONCLUSIONS: Pre-operative recruitment to the study was challenging;
      however, the lack of significant changes in blood cytokine levels and
      neuropsychological tests at T2 implies that post surgery may be a valid baseline
      assessment, but this needs further investigation in a larger study. The
      preliminary results support the hypothesis that chemotherapy induced fatigue is
      mediated by a change in peripheral cytokine levels which could explain some
      symptoms of 'chemo brain' experienced by patients.

PMID- 27047718
TI  - Evaluation of groundwater pollution in a mining area using analytical solution: a
      case study of the Yimin open-pit mine in China.
AB  - INTRODUCTION: This study focused on using analytical and numerical models to
      develop and manage groundwater resources, and predict the effects of management
      measurements in the groundwater system. Movement of contaminants can be studied
      based on groundwater flow characteristics. This study can be used for prediction
      of ion concentration and evaluation of groundwater pollution as the theoretical
      basis. CASE DESCRIPTION: The Yimin open-pit mine is located in the northern part
      of the Inner Mongolia Autonomous Region of China. High concentrations of iron and
      manganese are observed in Yimin open-pit mine because of exploitation and pumping
      that have increased the concentration of the ions in groundwater. In this study,
      iron was considered as an index of contamination, and the solute model was
      calibrated using concentration observations from 14 wells in 2014. DISCUSSION AND
      EVALUATION: The groundwater flow model and analytical solutions were used in this
      study to forecast pollution concentration and variation trend after calibration.
      With continuous pumping, contaminants will migrate, and become enriched, towards
      the wellhead in the flow direction. The concentration of the contaminants and the
      range of pollution increase with the flow rate increased. CONCLUSIONS: The
      suitable flow rate of single well should be <380 m/day at Yimin open-pit for the
      standard value of pollution concentration.

PMID- 27047719
TI  - FPGA implemented testbed in 8-by-8 and 2-by-2 OFDM-MIMO channel estimation and
      design of baseband transceiver.
AB  - In this study, a baseband OFDM-MIMO framework with channel timing and estimation
      synchronization is composed and executed utilizing the FPGA innovation. The
      framework is prototyped in light of the IEEE 802.11a standard and the signals
      transmitted and received utilizing a data transmission of 20 MHz. With the
      assistance of the QPSK tweak, the framework can accomplish a throughput of 24
      Mbps. Besides, the LS formula is executed and the estimation of a frequency
      specific fading channel is illustrated. For the rough estimation of timing, MNC
      plan is examined and actualized. Above all else, the whole framework is
      demonstrated in MATLAB and a drifting point model is set up. At that point, the
      altered point model is made with the assistance of Simulink and Xilinx's System
      Generator for DSP. In this way, the framework is incorporated and actualized
      inside of Xilinx's ISE tools and focused to Xilinx Virtex 5 board. In addition,
      an equipment co-simulation is contrived to decrease the preparing time while
      figuring the BER of the fixed point model. The work concentrates on above all
      else venture for further examination of planning creative channel estimation
      strategies towards applications in the fourth era (4G) mobile correspondence
      frameworks. 

PMID- 27047720
TI  - Identification of suitable sites for mountain ginseng cultivation using GIS and
      geo-temperature.
AB  - This study was conducted to explore an accurate site identification technique
      using a geographic information system (GIS) and geo-temperature (gT) for locating
      suitable sites for growing cultivated mountain ginseng (CMG; Panax ginseng),
      which is highly sensitive to the environmental conditions in which it grows. The
      study site was Jinan-gun, South Korea. The spatial resolution for geographic data
      was set at 10 m * 10 m, and the temperatures for various climatic factors
      influencing CMG growth were calculated by averaging the 3-year temperatures
      obtained from the automatic weather stations of the Korea Meteorological
      Administration. Identification of suitable sites for CMG cultivation was
      undertaken using both a conventional method and a new method, in which the gT was
      added as one of the most important factors for crop cultivation. The results
      yielded by the 2 methods were then compared. When the gT was added as an
      additional factor (new method), the proportion of suitable sites identified
      decreased by 0.4 % compared with the conventional method. However, the proportion
      matching real CMG cultivation sites increased by 3.5 %. Moreover, only 68.2 %
      corresponded with suitable sites identified using the conventional factors; i.e.,
      31.8 % were newly detected suitable sites. The accuracy of GIS-based
      identification of suitable CMG cultivation sites improved by applying the
      temperature factor (i.e., gT) in addition to the conventionally used factors. 

PMID- 27047721
TI  - Survival in patients with non-metastatic breast cancer treated with adjuvant
      trastuzumab in clinical practice.
AB  - PURPOSE: The NSABP Trial B-31 and NCCTG Trial N9831 (B-31/N9831 trials, Romond et
      al. in N Engl J Med 353:1673-84, 2005. doi:10.1056/NEJMoa052122; Perez et al. in
      J Clin Oncol 32:3744-52, 2014. doi:10.1200/JCO.2014.55.5730) established the
      efficacy of adjuvant trastuzumab for patients with HER2-positive early stage
      breast cancer. We aimed to estimate the overall survival (OS) and relapse-free
      survival (RFS) of HER2-positive non-metastatic breast cancer patients treated
      with adjuvant trastuzumab in a clinical practice setting in the United States.
      METHODS: Adult women initiating adjuvant trastuzumab within 1 year of breast
      cancer surgery were identified in the health claims database of the US Department
      of Defense (01/2003-12/2012). OS and RFS unadjusted rates at 4 and 6 years after
      the first trastuzumab treatment following the breast cancer diagnosis were
      estimated from Kaplan-Meier analyses. RESULTS: The study sample included 3188
      women followed for a median of 3.3 years after trastuzumab initiation and treated
      continuously with trastuzumab for a median of 12 months. The OS rates (95 %
      confidence intervals) at 4 and 6 years were 90.0 % (88.6-91.2) and 87.1 (85.3
      88.6), respectively. The corresponding RFS rates were 75.8 % (74.0-77.5) and 72.7
      (70.7-74.7), respectively. The OS and RFS rates at 6 years reported in the B
      31/N9831 trials were 89.8 and 81.4 %, respectively. CONCLUSIONS: OS rates
      estimated in this study were in range with those estimated in the B-31/N9831
      trials, while RFS rates were lower. However, patients in the B-31/N9831 trials
      were younger and possibly had fewer comorbidities than patients in the current
      study; these differences were not adjusted for in the crude OS and RFS analyses.

PMID- 27047722
TI  - Coexistence of contralateral cluster headache and probable paroxysmal hemicrania:
      a case report.
AB  - INTRODUCTION: The trigeminal autonomic cephalagias (TACs) are short-lasting
      unilateral headaches associated with autonomic features. Even if coexistence of
      different ipsilateral TACs in the same patient has been previously reported in
      few papers, the simultaneous occurrence of contralateral TACs is not described
      previously. CASE DESCRIPTION: A 50 years old working man complained, at the end
      of his cluster period, a new TAC, fitting the criteria for probable paroxysmal
      hemicrania. The dramatic improvement of this last cephalalgia with indomethacin
      treatment confirmed the diagnosis. DISCUSSION EVALUATION AND CONCLUSION: There is
      a clear overlap in clinical diagnosis between cluster headache (CH) and
      paroxysmal hemicrania (PH) and similarities are somewhat greater than
      differences. The originality of this report is the coexistence of contralateral
      TACs in the same patients at the same moment. According neuroimaging studies, CH
      hypothalamic activation occurs ipsilateral to the side of the headache while in
      PH hypothalamic activation occurs contralateral to the side of headache. It could
      be suggested that a continuous hypothalamic activation give a maladaptive
      plasticity recruiting closed neuronal aggregates responsible for the developing
      of PH after a long period of CH, confirming the central origin of both CH and PH.
      Further studies need to confirm this hypothesis.

PMID- 27047723
TI  - Effects of biochar and alkaline amendments on cadmium immobilization, selected
      nutrient and cadmium concentrations of lettuce (Lactuca sativa) in two
      contrasting soils.
AB  - To assess the efficiency of seven treatments including biochars produced from
      dried faecal matter and manures as stabilizing agents of cadmium (Cd)-spiked
      soils, lettuce was grown in glasshouse on two contrasting soils. The soils used
      were moderately fertile silty loam and less fertile sandy loam and the applied
      treatments were 7 % w/w. The reduction of bioavailable Cd (ammonium nitrate
      extractable) and its phytoavailability for lettuce were used as assessment
      criteria in the evaluation of stabilization performance of each treatment.
      Moreover, the agronomic values of the treatments were also investigated. Ammonium
      nitrate extraction results indicated that faecal matter biochar, cow manure
      biochar and lime significantly reduced bioavailable Cd by 84-87, 65-68 and 82-91
      %, respectively, as compared to the spiked controls. Unpredictably, coffee husk
      biochar induced significant increment of Cd in NH4NO3 extracts. The
      immobilization potential of faecal matter biochar and lime were superior than the
      other treatments. However, lime and egg shell promoted statistically lower yield
      and P, K and Zn concentrations response of lettuce plants compared to the biochar
      treatments. The lowest Cd and highest P tissue concentrations of lettuce plants
      were induced by faecal matter and cow manure biochar treatments in both soils.
      Additionally, the greatest Cd phytoavailability reduction for lettuce was induced
      by poultry litter and cow manure biochars in the silty loam soil. Our results
      indicate that faecal matter and animal manure biochars have shown great potential
      to promote Cd immobilization and lettuce growth response in heavily contaminated
      agricultural fields. 

PMID- 27047724
TI  - Isolated radial scar diagnosis by core-needle biopsy: Is surgical excision
      necessary?
AB  - PURPOSE: Radial scar and radial sclerosis (RS) are considered benign breast
      lesions with proliferative features. There is sparse literature on frequency of
      cancer upgrade in these patients without atypical features found on image-guided
      needle biopsy. This study retrospectively reviews cases of isolated RS diagnosed
      on needle biopsy and evaluates the cancer upgrade after subsequent surgical
      excision. METHODS: We conducted a retrospective cross-sectional study of cases
      with an isolated RS diagnosis based on needle biopsy and subsequent surgical
      pathology among all patients between January 1, 2009 and December 31, 2013.
      Patients with concomitant atypia, lobular carcinoma in situ on core biopsy,
      complete excision of very small RS with needle biopsy, and radiology-pathology
      discordance were excluded. An upgrade from the needle biopsy of RS was defined as
      surgical excision pathology that revealed ductal carcinoma in situ (DCIS),
      invasive ductal carcinoma (IDC), and/or invasive lobular carcinoma (ILC).
      RESULTS: 10,921 image-guided needle biopsy pathology reports were collected and
      88 patients (0.81 %) were identified as having isolated RS. Of these 88 patients,
      63 (72 %) underwent excision. The upgrade rate to cancer on subsequent surgical
      excision was 1.59 % (1/63) for DCIS; 0 % (0/63) for IDC; and 0 % (0/63) ILC.
      Twenty-five patients who did not undergo surgical excision had stable imaging
      studies with mean (+/-SD) 26 (+/-20) months follow up. CONCLUSIONS: Isolated
      radial scar on needle biopsy may not warrant routine surgical excision given
      relatively low cancer upgrade rates. Advancement in breast imaging, pathology and
      multidisciplinary approaches to care may effectively guide non-surgical
      management of RS.

PMID- 27047725
TI  - Congruences for central factorial numbers modulo powers of prime.
AB  - Central factorial numbers are more closely related to the Stirling numbers than
      the other well-known special numbers, and they play a major role in a variety of
      branches of mathematics. In the present paper we prove some interesting
      congruences for central factorial numbers. 

PMID- 27047726
TI  - Stereoselectively synthesis and structural confirmation of dehydrodipeptides with
      dehydrobutyrine.
AB  - Most of polypeptides containing alpha,beta-dehydroamino acids have important
      biological activity, so exploration of synthetic method has practical
      significance. In this paper, dipeptides were prepared from l-threonine by
      protecting of c-terminal allyl acetate, and condensing reaction with a series of
      N-Boc amino acid. Then, treatment of dipeptides obtained with DMAP, (Boc)2O and
      tetramethylguanidine in the acetonitrile occured beta-elimination reaction to
      yield stereoselectively dehydrodipeptides. Structures of dehydrodipeptides were
      confirmed by (1)H NMR, (13)C NMR and MS. Analysis of (1)H NMR, 2D NMR and crystal
      structure showed that the dehydrodipeptides were Z-configuration.Graphical
      abstractDehydrodipeptides were prepared from l-threonine. Their structures were
      confirmed by (1)H NMR, (13)C NMR and MS. 

PMID- 27047727
TI  - Identification of bacterial communities in sediments of Poyang Lake, the largest
      freshwater lake in China.
AB  - Bacteria play a vital role in various biogeochemical processes in lacustrine
      sediment ecosystems. This study is among the first to investigate the spatial
      distribution patterns of bacterial community composition in the sediments of
      Poyang Lake, the largest freshwater lake of China. Sediment samples were
      collected from the main basins and mouths of major rivers that discharge into the
      Poyang Lake in May 2011. Quantitative PCR assay and pyrosequencing analysis of
      16S rRNA genes showed that the bacteria community abundance and compositions of
      Poyang Lake sediment varied largely among sampling sites. A total of 25 phyla and
      68 bacterial orders were distinguished. Burkholderiales, Gallionellales (Beta
      proteobacteria), Myxococcales, Desulfuromonadales (Delta-proteobacteria),
      Sphingobacteriales (Bacteroidetes), Nitrospirales (Nitrospirae), Xanthomonadales
      (Gamma-proteobacteria) were identified as the major taxa and collectively
      accounted for over half of annotated sequences. Moreover, correlation analyses
      suggested that higher loads of total phosphorus and heavy metals (copper, zinc
      and cadmium) could enhance bacterial abundance in the sediment. 

PMID- 27047728
TI  - Economic evaluation of the air pollution effect on public health in China's 74
      cities.
AB  - Air deterioration caused by pollution has harmed public health. The existing
      studies on the economic loss caused by a variety of air pollutants in multiple
      cities are lacking. To understand the effect of different pollutants on public
      health and to provide the basis of the environmental governance for governments,
      based on the dose-response relation and the willingness to pay, this paper used
      the latest available data of the inhalable particulate matter (PM10) and sulphur
      dioxide (SO2) from January 2015 to June 2015 in 74 cities by establishing the
      lowest and the highest limit scenarios. The results show that (1) in the lowest
      and highest limit scenario, the health-related economic loss caused by PM10 and
      SO2 represented 1.63 and 2.32 % of the GDP, respectively; (2) For a single city,
      in the lowest and the highest limit scenarios, the highest economic loss of the
      public health effect caused by PM10 and SO2 was observed in Chongqing; the
      highest economic loss of the public health effect per capita occurred in Hebei
      Baoding. The highest proportion of the health-related economic loss accounting
      for GDP was found in Hebei Xingtai. The main reason is that the terrain
      conditions are not conducive to the spread of air pollutants in Chongqing,
      Baoding and Xingtai, and the three cities are typical heavy industrial cities
      that are based on coal resources. Therefore, this paper proposes to improve the
      energy structure, use the advanced production process, reasonably control the
      urban population growth, and adopt the emissions trading system in order to
      reduce the economic loss caused by the effects of air pollution on public health.

PMID- 27047729
TI  - Advances on image interpolation based on ant colony algorithm.
AB  - This paper presents an advance on image interpolation based on ant colony
      algorithm (AACA) for high resolution image scaling. The difference between the
      proposed algorithm and the previously proposed optimization of bilinear
      interpolation based on ant colony algorithm (OBACA) is that AACA uses global
      weighting, whereas OBACA uses local weighting scheme. The strength of the
      proposed global weighting of AACA algorithm depends on employing solely the
      pheromone matrix information present on any group of four adjacent pixels to
      decide which case deserves a maximum global weight value or not. Experimental
      results are further provided to show the higher performance of the proposed AACA
      algorithm with reference to the algorithms mentioned in this paper. 

PMID- 27047730
TI  - Hybrid regularizers-based adaptive anisotropic diffusion for image denoising.
AB  - To eliminate the staircasing effect for total variation filter and synchronously
      avoid the edges blurring for fourth-order PDE filter, a hybrid regularizers-based
      adaptive anisotropic diffusion is proposed for image denoising. In the proposed
      model, the [Formula: see text]-norm is considered as the fidelity term and the
      regularization term is composed of a total variation regularization and a fourth
      order filter. The two filters can be adaptively selected according to the
      diffusion function. When the pixels locate at the edges, the total variation
      filter is selected to filter the image, which can preserve the edges. When the
      pixels belong to the flat regions, the fourth-order filter is adopted to smooth
      the image, which can eliminate the staircase artifacts. In addition, the split
      Bregman and relaxation approach are employed in our numerical algorithm to speed
      up the computation. Experimental results demonstrate that our proposed model
      outperforms the state-of-the-art models cited in the paper in both the
      qualitative and quantitative evaluations. 

PMID- 27047731
TI  - Quantitative analysis of orthopedic metal artefact reduction in 64-slice computed
      tomography scans in large head metal-on-metal total hip replacement, a phantom
      study.
AB  - PURPOSE: Quantification of the effect of O-MAR on decreasing metal artefacts
      caused by large head metal on metal total hip arthroplasty (MoM THA) in a
      dedicated phantom setup of the hip. BACKGROUND: Pathological reactions of the hip
      capsule on Computed tomography (CT) can be difficult to diagnose due to different
      metal artefacts. The O-MAR algorithm deploys an iterative loop where the metal
      sinogram is identified, extracted, and subsequently serves as a mask to correct
      the measured sinogram. Main goal of this study is to quantify the ability of the
      O-MAR technique to correct deviation in medullary bone attenuation caused by
      streak artefacts from the large-head MoM THA embedded in a phantom. Secondary
      goal is to evaluate the influence of O-MAR on CNR. METHODS: The phantom was
      designed as a Perspex box (PMMA) containing water and a supplementary MOM THA
      surrounded by Perspex columns comprising calibrated calcium pellets. Each column
      contains 200 mg of hydroxyapatite/calcium carbonate to simulate healthy bone
      tissue. Scans were obtained with and without a MoM THA at different dose levels.
      Different reconstructions were made with filter A, iDose(4) level 5 and with and
      without O-MAR. The scans without the prosthesis were used as the baseline.
      Information about the attenuation in Hounsfield units, image noise in standard
      deviation within the ROI's were extracted and the CNR was calculated. RESULTS:
      Pellet L0 and R0 (proximal of the MoM THA) were defined as reference, lacking any
      disturbance by metal artefacts; L5, L6 and L8 were respectively visually
      categorized as 'light' 'medium' and 'heavy disturbance'. Significant improvements
      in attenuation deviation caused by metal artefact were 43, 68 and 32 %, for
      respectively pellet L5, L6 and L8 (p < 0.001). Significant CNR improvements were
      present for L5 and L6 and were respectively 72 and 52 % (p < 0.001). O-MAR showed
      no improvement on CNR for L8. CONCLUSION: This phantom study significantly
      increases image quality by the use of O-MAR in the presence of metal artefacts by
      significantly reducing metal artefacts subsequently and increasing CNR on a 64
      slice CT system in light and medium disturbance of the image.

PMID- 27047732
TI  - A catalog of automated analysis methods for enterprise models.
AB  - Enterprise models are created for documenting and communicating the structure and
      state of Business and Information Technologies elements of an enterprise. After
      models are completed, they are mainly used to support analysis. Model analysis is
      an activity typically based on human skills and due to the size and complexity of
      the models, this process can be complicated and omissions or miscalculations are
      very likely. This situation has fostered the research of automated analysis
      methods, for supporting analysts in enterprise analysis processes. By reviewing
      the literature, we found several analysis methods; nevertheless, they are based
      on specific situations and different metamodels; then, some analysis methods
      might not be applicable to all enterprise models. This paper presents the work of
      compilation (literature review), classification, structuring, and
      characterization of automated analysis methods for enterprise models, expressing
      them in a standardized modeling language. In addition, we have implemented the
      analysis methods in our modeling tool. 

PMID- 27047734
TI  - Enzymatic activity in the presence of surfactants commonly used in dissolution
      media, Part 1: Pepsin.
AB  - The United States Pharmacopeia (USP) General Chapters Dissolution <711> and
      Disintegration and Dissolution of Dietary Supplements <2040> allows the use of
      enzymes in dissolution media when gelatin capsules do not conform to dissolution
      specifications due to cross linking. Possible interactions between enzymes and
      surfactants when used together in dissolution media could result in loss of the
      enzymatic activity. Pepsin is an enzyme commonly used in dissolution media, and
      in this work, the activity of pepsin was determined in the presence of different
      surfactants as usually found in case of dissolution tests of certain gelatin
      capsule formulations. Pepsin enzymatic activity was determined according to the
      Ninth Edition of the Food Chemicals Codex (FCC) 9 method, in dissolution
      conditions: simulated gastric fluid, 37  degrees C and 50 rpm. Sodium dodecyl
      sulfate (SDS), cetyltrimethyl ammonium bromide (CTAB), polysorbate 80 (Tween 80)
      and octoxynol 9 (Triton X100) in concentrations above and below their critical
      micellar concentrations were selected. Results showed a significant reduction in
      the activity of pepsin at all the concentrations of SDS assayed. On the contrary,
      CTAB, Tween 80, and Triton X100 did not alter the enzymatic activity at of pepsin
      any of the concentration assayed. This data demonstrates a rational selection of
      the surfactant to be used when pepsin is required in dissolution test. 

PMID- 27047733
TI  - Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and
      Regeneration.
AB  - Platelet rich blood derivatives have been widely used in different fields of
      medicine and stem cell based tissue engineering. They represent natural cocktails
      of autologous growth factor, which could provide an alternative for recombinant
      protein based approaches. Platelet rich blood derivatives, such as platelet rich
      plasma, have consistently shown to potentiate stem cell proliferation, migration,
      and differentiation. Here, we review the spectrum of platelet rich blood
      derivatives, discuss their current applications in tissue engineering and
      regenerative medicine, reflect on their effect on stem cells, and highlight
      current translational challenges.

PMID- 27047735
TI  - Germ cell-specific expression of Cre recombinase using the VASA promoter in the
      pig.
AB  - The Cre-loxP system is a powerful tool for genetic analysis of distinct cell
      lineages and tissue-specific gene knockout in animal models. VASA is specifically
      expressed in reproductive tissues, and is known to play important roles in
      spermatogenesis and germ-cell growth. In this study, Cre recombinase transgenic
      pigs under the control of the VASA promoter were generated by somatic cell
      nuclear transfer. Germ cell-specific expression of Cre recombinase in VASA-Cre
      transgenic pigs was shown by western blotting and immunohistochemistry. VASA-Cre
      transgenic pigs will be a useful tool for germ cell-specific gene knockout and a
      disease model for disorders of the reproductive system. 

PMID- 27047736
TI  - Cell-free synthesis of isotopically labelled peptide ligands for the functional
      characterization of G protein-coupled receptors.
AB  - Cell-free systems exploit the transcription and translation machinery of cells
      from different origins to produce proteins in a defined chemical environment. Due
      to its open nature, cell-free protein production is a versatile tool to introduce
      specific labels such as heavy isotopes, non-natural amino acids and tags into the
      protein while avoiding cell toxicity. In particular, radiolabelled peptides and
      proteins are valuable tools for the functional characterization of protein
      protein interactions and for studying binding kinetics. In this study we
      evaluated cell-free protein production for the generation of radiolabelled
      ligands for G protein-coupled receptors (GPCRs). These receptors are seven
      transmembrane-domain receptors activated by a plethora of extracellular stimuli
      including peptide ligands. Many GPCR peptide ligands contain disulphide bonds and
      are thus inherently difficult to produce in bacterial expression hosts or in
      Escherichia coli-based cell-free systems. Here, we established an adapted E. coli
      based cell-free translation system for the production of disulphide bond
      containing GPCR peptide ligands and specifically introduce tritium labels for
      detection. The bacterial oxidoreductase DsbA is used as a chaperone to favour the
      formation of disulphide bonds and to enhance the yield of correctly folded
      proteins and peptides. We demonstrate the correct folding and formation of
      disulphide bonds and show high-affinity ligand binding of the produced radio
      peptide ligands to the respective receptors. Thus, our system allows the fast,
      cost-effective and reliable synthesis of custom GPCR peptide ligands for
      functional and structural studies. 

PMID- 27047737
TI  - A specific role for PRND in goat foetal Leydig cells is suggested by prion family
      gene expression during gonad development in goats and mice.
AB  - Three genes of the prion protein gene family are expressed in gonads. Comparative
      analyses of their expression patterns in mice and goats revealed constant
      expression of PRNP and SPRN in both species and in both male and female gonads,
      but with a weaker expression of SPRN. By contrast, expression of PRND was found
      to be sex-dimorphic, in agreement with its role in spermatogenesis. More
      importantly, our study revealed that PRND seems to be a key marker of foetal
      Leydig cells specifically in goats, suggesting a yet unknown role for its encoded
      protein Doppel during gonadal differentiation in nonrodent mammals.

PMID- 27047738
TI  - Double-strand break repair based on short-homology regions is suppressed under
      terminal deoxynucleotidyltransferase expression, as revealed by a novel vector
      system for analysing DNA repair by nonhomologous end joining.
AB  - We have constructed a novel, nonhomologous end-joining (NHEJ) assay vector (NAV),
      containing mKate2, Venus and ccdB genes. Cotransfection of NAV with a construct
      expressing the restriction enzyme I-SceI generated a double-strand break (DSB) in
      NAV that excised mKate2 and ccdB. Repair of this DSB produced an intact vector
      that expressed Venus, a green fluorescent protein. Because cells bearing the
      repaired NAV lacked the ccdB gene which slows cell proliferation, the cultures
      were enriched in cells containing repaired DSBs. DNA sequence analysis of the DSB
      junctions indicated that the repair was carried out mainly by using the closest
      homology sequence. Use of the NAV yielded rapid results within 3 days after
      transfection. We then used the NAV to analyse NHEJ in cells overexpressing
      terminal deoxynucleotidyltransferase (TdT). The results indicated that TdT
      suppresses DNA repair that is based on short (one- or two-base) homology regions,
      to efficiently add deoxynucleotides during VDJ recombination in lymphoid cells. 

PMID- 27047739
TI  - Three-step procedure for preparation of pure Bacillus altitudinis ribonuclease.
AB  - Ribonucleases are considered as promising tools for anticancer treatment due to
      their selective cytotoxicity against tumor cells. We investigated a new RNase
      from Bacillus altitudinis termed BALNASE (B. altitudinis RNase). Balnase is a
      close homolog of the well-known cytotoxic binase, differing by only one amino
      acid residue: nonpolar hydrophobic alanine at position 106 in the balnase
      molecule is replaced by a polar uncharged threonine in binase. The most exciting
      question is how the physico-chemical properties and biological effects of RNase
      might be changed by A106T substitution. Here, we have developed a chromatography
      based rapid and modern technique for the purification of this new RNase which
      allowed us to get a protein sample of high quality with specific activity of 1.2
      * 10(6) units in preparative amounts, suitable for further investigation of its
      biological properties. 

PMID- 27047740
TI  - Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and
      tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.
AB  - Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with
      vital roles in proliferation, differentiation and apoptosis. In this study, we
      have examined the role of its C-terminal domain (YB1 CTD) in proliferation,
      angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3
      was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell
      proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR
      3 cells. YB1 CTD overexpression changed the cytoskeletal organization and
      slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited
      secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced
      EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression
      attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and
      decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3
      tumour-bearing mice. Taken together, our findings demonstrate the vital role of
      YB1 CTD overexpression in inhibiting proliferation, angiogenesis and
      tumorigenicity of breast cancer cell line SK-BR-3. 

PMID- 27047741
TI  - mTORC1 is involved in the regulation of branched-chain amino acid catabolism in
      mouse heart.
AB  - The branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex regulates
      branched-chain amino acid (BCAA) catabolism by controlling the second step of
      this catabolic pathway. In the present study, we examined the in vivo effects of
      treatment with an mTORC1 inhibitor, rapamycin, on cardiac BCKDH complex activity
      in mice. Oral administration of leucine in control mice significantly activated
      the cardiac BCKDH complex with an increase in cardiac concentrations of leucine
      and alpha-ketoisocaproate. However, rapamycin treatment significantly suppressed
      the leucine-induced activation of the complex despite similar increases in
      cardiac leucine and alpha-ketoisocaproate levels. Rapamycin treatment fully
      inhibited mTORC1 activity, measured by the phosphorylation state of ribosomal
      protein S6 kinase 1. These results suggest that mTORC1 is involved in the
      regulation of cardiac BCAA catabolism. 

PMID- 27047742
TI  - In utero TNF-alpha treatment induces telomere shortening in young adult mice in
      an ATF7-dependent manner.
AB  - Epidemiological studies indicate that exposure to stress during intrauterine life
      is associated with shorter telomeres in young adulthood, and a correlation
      between telomere length in early life and lifespan has been suggested. However,
      empirical studies evaluating these phenomena have not been performed, and the
      mechanism of stress-induced telomere shortening remains unknown. Since the level
      of tumour necrosis factor alpha (TNF-alpha) in peripheral blood cells is
      increased by various psychological stresses, the effect of TNF-alpha
      administration to pregnant mice on telomere length in adulthood was examined in
      the present study. In utero TNF-alpha treatment-induced telomere shortening in
      adult mice. Telomere shortening was observed in certain tissues such as the bone
      marrow, spleen, and lung, and was detected at specific age ranges during
      adulthood. Telomere shortening was not observed in mice lacking the stress
      responsive transcription factor ATF7, which contributes to heterochromatin
      formation in the absence of stress. The present study identified the conditions
      under which in utero TNF-alpha treatment induces telomere shortening in
      adulthood.

PMID- 27047743
TI  - Intestinal removal of free fatty acids from hosts by Lactobacilli for the
      treatment of obesity.
AB  - Recent findings on the association of gut microbiota with various diseases,
      including obesity, prompted us to investigate the possibility of using a certain
      type of gut bacteria as a safe therapeutic for obesity. Lactobacillus mutants
      with enhanced capacity in absorption of free fatty acids (FFAs) were isolated to
      show reduced absorption of FFAs by the administered host, attributing to
      inhibition of body weight gain and body fat accumulation as well as amelioration
      of blood profiles. Consequently, high throughput screening of natural FFAs
      absorbing intestinal microbes led to the isolation of Lactobacillus reuteri JBD30
      l. The administration of Lactobacillus JBD30l lowered the concentration of FFAs
      in the gut fluid content of small intestine, thus reducing intestinal absorption
      of FFAs whereas promoting fecal excretion of FFAs. Animal data also confirmed
      that the efficacy of Lactobacillus JBD30l on body weight similar to that of
      orlistat, an FDA-approved pharmaceutical for long-term use to treat obesity. In a
      subsequent random, double-blind, placebo-controlled clinical trial (KCT0000452 at
      Clinical Research Information Service of Korea), there was a statistically
      significant difference in the percentage change in body weight between the
      Lactobacillus JBD301 and the placebo group (P = 0.026) as well as in the BMI (P =
      0.036) from the 0-week assessment to the 12-week assessment. Our results show
      that FFA-absorbing Lactobacillus JBD301 effectively reduces dietary fat
      absorption, providing an ideal treatment for obesity with inherent safety. 

PMID- 27047744
TI  - Analysis of nucleotide diphosphate sugar dehydrogenases reveals family and group
      specific relationships.
AB  - UDP-glucose dehydrogenase (UDPGDH), UDP-N-acetyl-mannosamine dehydrogenase
      (UDPNAMDH) and GDP-mannose dehydrogenase (GDPMDH) belong to a family of NAD (+)
      linked 4-electron-transfering oxidoreductases called nucleotide diphosphate sugar
      dehydrogenases (NDP-SDHs). UDPGDH is an enzyme responsible for converting UDP-d
      glucose to UDP-d-glucuronic acid, a product that has different roles depending on
      the organism in which it is found. UDPNAMDH and GDPMDH convert UDP-N-acetyl
      mannosamine to UDP-N-acetyl-mannosaminuronic acid and GDP-mannose to GDP
      mannuronic acid, respectively, by a similar mechanism to UDPGDH. Their products
      are used as essential building blocks for the exopolysaccharides found in
      organisms like Pseudomonas aeruginosa and Staphylococcus aureus. Few studies have
      investigated the relationships between these enzymes. This study reveals the
      relationships between the three enzymes by analysing 229 amino acid sequences.
      Eighteen invariant and several other highly conserved residues were identified,
      each serving critical roles in maintaining enzyme structure, coenzyme binding or
      catalytic function. Also, 10 conserved motifs that included most of the conserved
      residues were identified and their roles proposed. A phylogenetic tree
      demonstrated relationships between each group and verified group assignment.
      Finally, group entropy analysis identified novel conservations unique to each NDP
      SDH group, including residue positions critical to NDP-sugar substrate
      interaction, enzyme structure and intersubunit contact. These positions may serve
      as targets for future research. ENZYMES: UDP-glucose dehydrogenase (UDPGDH, EC
      1.1.1.22).

PMID- 27047745
TI  - The 2.2-Angstrom resolution crystal structure of the carboxy-terminal region of
      ataxin-3.
AB  - An expansion of polyglutamine (polyQ) sequence in ataxin-3 protein causes
      spinocerebellar ataxia type 3, an inherited neurodegenerative disorder. The
      crystal structure of the polyQ-containing carboxy-terminal fragment of human
      ataxin-3 was solved at 2.2-A resolution. The Atxn3 carboxy-terminal fragment
      including 14 glutamine residues adopts both random coil and alpha-helical
      conformations in the crystal structure. The polyQ sequence in alpha-helical
      structure is stabilized by intrahelical hydrogen bonds mediated by glutamine side
      chains. The intrahelical hydrogen-bond interactions between glutamine side chains
      along the axis of the polyQ alpha-helix stabilize the secondary structure.
      Analysis of this structure furthers our understanding of the polyQ-structural
      characteristics that likely underlie the pathogenesis of polyQ-expansion
      disorders.

PMID- 27047746
TI  - Inhibition of Src homology 2 domain-containing phosphatase 1 increases insulin
      sensitivity in high-fat diet-induced insulin-resistant mice.
AB  - Insulin resistance plays a crucial role in the development of type 2 diabetes.
      Insulin receptor signalling is antagonized and tightly controlled by protein
      tyrosine phosphatases (PTPs). However, the precise role of the PTP src homology 2
      domain-containing phosphatase 1 (SHP-1) in insulin resistance has not been
      explored. Male C57BL/6J mice were fed a high-fat diet (HFD, 60% kcal from fat),
      to induce insulin resistance, or a low-fat diet (LFD, 10% kcal from fat) for 10
      weeks. Afterwards, HFD-fed mice were pharmacologically treated with the SHP-1
      (Ptpn6) inhibitor sodium stibogluconate and the broad spectrum pan-PTP inhibitor
      bis(maltolato)oxovanadium(IV) (BMOV). Both inhibitors ameliorated the metabolic
      phenotype, as evidenced by reduced body weight, improved insulin sensitivity and
      glucose tolerance, which was not due to altered PTP gene expression. In parallel,
      phosphorylation of the insulin receptor and of the insulin signalling key
      intermediate Akt was enhanced, and both PTP inhibitors and siRNA-mediated SHP-1
      downregulation resulted in an increased glucose uptake in vitro. Finally,
      recombinant SHP-1 was capable of dephosphorylating the ligand-induced tyrosine
      phosphorylated insulin receptor. These results indicate a central role of SHP-1
      in insulin signalling during obesity, and SHP-1 inhibition as a potential
      therapeutic approach in metabolic diseases. 

PMID- 27047747
TI  - High expression of Fatty Acid-Binding Protein 5 promotes cell growth and
      metastatic potential of colorectal cancer cells.
AB  - Fatty acid-binding proteins (FABPs) are responsible for binding and storing
      hydrophobic ligands such as long-chain fatty acids, and for transporting these
      ligands to the appropriate compartments within the cell. The present study
      demonstrates that the FABP5 gene is upregulated in colorectal cancer cells
      compared to normal colon cells in a manner that correlates with disease stage and
      that FABP5 significantly promotes colorectal cancer cell growth and metastatic
      potential. Thus, FABP5 might be a promising prognostic or therapeutic biomarker
      candidate in human colorectal cancer.

PMID- 27047748
TI  - A novel zinc-binding alcohol dehydrogenase 2 from Arachis diogoi, expressed in
      resistance responses against late leaf spot pathogen, induces cell death when
      transexpressed in tobacco.
AB  - A novel zinc-binding alcohol dehydrogenase 2 (AdZADH2) was significantly
      upregulated in a wild peanut, Arachis diogoi treated with conidia of late leaf
      spot (LLS) pathogen, Phaeoisariopsis personata. This upregulation was not
      observed in a comparative analysis of cultivated peanut, which is highly
      susceptible to LLS. This zinc-binding alcohol dehydrogenase possessed a Rossmann
      fold containing NADB domain in addition to the MDR domain present in all
      previously characterized plant ADH genes/proteins. Transient over-expression of
      AdZADH2 under an estradiol inducible promoter (XVE) resulted in hypersensitive
      response (HR)-like cell death in tobacco leaf. However, the same level of cell
      death was not observed when the domains were transiently expressed individually.
      Cell death observed in tobacco was associated with overexpression of cell death
      related proteins, antioxidative enzymes such as SOD, CAT and APX and pathogenesis
      related (PR) proteins. In A. diogoi, AdZADH2 expression was significantly
      upregulated in response to the plant signaling hormones salicylic acid, methyl
      jasmonate, and sodium nitroprusside. 

PMID- 27047749
TI  - Further study of circulating IgG antibodies to CD25-derived peptide antigens in
      nonsmall cell lung cancer.
AB  - A recent study reported that circulating antibodies to CD25-derived peptide
      antigens were significantly higher in patients with nonsmall cell lung cancer
      (NSCLC) than control subjects. The present study was, thus, undertaken to
      replicate the initial finding with different sample sets. An in-house ELISA was
      applied to determine circulating IgG antibodies to linear peptide antigens
      derived from CD25. A total of 111 patients with NSCLC and 216 control subjects
      were recruited and divided into the discovery sample (51 vs 108) and the
      validation sample (60 vs 108) based on the time of sampling. Student's t test
      showed that circulating anti-CD25 IgG levels were significantly higher in the
      patient group than the control group (t = 2.23, P = 0.027) and the validation
      sample replicated this finding (t = 3.31, P = 0.0012), generating a combined P
      value of 0.0004 (chi(2) = 20.8, df = 4). Fisher's combining probability revealed
      that patients with stage IV NSCLC had a significant increase in anti-CD25 IgG
      levels compared with control subjects (chi(2) = 22.1, df = 4, P = 0.0002) but
      those with the other three stages did not. This study suggests that circulating
      anti-CD25 IgG antibodies may have prognostic rather than early diagnostic values
      for lung cancer. 

PMID- 27047750
TI  - Experimentally optimized threading structures of the proton-coupled folate
      transporter.
AB  - The proton-coupled folate transporter (PCFT, SLC46A1) transports folic acid
      across the plasma membrane, together with an excess of protons such that the net
      charge translocation is positive. We developed 3D structural models of PCFT
      threaded onto the X-ray structures of major facilitator superfamily (MFS) members
      that were identified as close structural homologues. The model of PCFT threaded
      onto the glycerol-3-phosphate transporter (GlpT) structure is consistent with
      detailed accessibility studies in the absence of extracellular substrate and at
      pH 7.4 presented here, and additionally with a multitude of other mutagenesis and
      functional studies. Characteristic MFS structural features are preserved in this
      PCFT model, such as 12 transmembrane helices divided into two pseudosymmetric
      bundles, and a high density of positive charges on the periphery of the
      cytoplasmic site that allow interactions with negatively charged lipid head
      groups. Under the experimental conditions, PCFT predominantly samples the resting
      state, which in this case is inward-open. Several positions lining the substrate
      cavity have been identified. Motif A, a helix-turn-helix motif that is a hallmark
      of MFS transporters between transmembrane segments II and III is oriented
      appropriately to interact with residues from transmembrane segments IV as well as
      XI upon conformational transition to the outward-open state. A charge-relay
      system between three charged residues as well as apposing glycines in two alpha
      helices, both contributed to by motif A, become engaged when PCFT is modeled on
      the outward-open state of a putative proton-driven transporter (YajR).

PMID- 27047751
TI  - Current strategies against invasive fungal infections in patients with aplastic
      anemia, strong power and weak weapon, a case report and review of literature.
AB  - We report an 18 year old boy with Aplastic anemia complicated by serious fungal
      rhinosinusitis. Despite prompt treatment and early repeated surgical
      debridements, he died after about more than 6 weeks of hard challenges with
      fungal infections. Current strategies against invasive fungal infections (IFIs)
      in patients with Aplastic anemia may be inadequate for the management of serious
      complications. Antifungal prophylaxis is highly recommended in pre-transplant
      period for severe form of Aplastic anemia. 

PMID- 27047752
TI  - Personal genomics: Where are we now?

PMID- 27047753
TI  - Beyond clinical utility: The multiple values of DTC genetics.
AB  - One point of consensus in the otherwise very controversial discussion about the
      benefits and dangers of DTC genetics in the health domain is the lack of
      substantial clinical utility. At the same time, both the empirical and conceptual
      literature indicate that health-related DTC tests can have value and utility
      outside of the clinic. We argue that a broader and multi-faceted
      conceptualization of utility and value would enrich the ethical and social
      discussion of DTC testing in several ways: First, looking at ways in which DTC
      testing can have personal and social value for users - in the form of
      entertainment, learning, or a way to relate to others - can help to explain why
      people still take DTC tests, and will, further down the line, foster a more
      nuanced understanding of secondary and tertiary uses of DTC test results (which
      could very well unearth new ethical and regulatory challenges). Second,
      considering the economic value and broader utility of DTC testing foregrounds
      wider social and political aspects than have been dominant in the ethical and
      regulatory debates surrounding DTC genetics so far. These wider political aspects
      include the profound power asymmetries that characterize the collection and use
      of personal genetic data in many contexts. 

PMID- 27047754
TI  - Attitudes towards personal genomics among older Swiss adults: An exploratory
      study.
AB  - OBJECTIVES: To explore attitudes of Swiss older adults towards personal genomics
      (PG). METHODS: Using an anonymized voluntary paper-and-pencil survey, data were
      collected from 151 men and women aged 60-89 years attending the
      Seniorenuniversitat Zurich, Switzerland (Seniors' University). Analyses were
      conducted using descriptive and inferential statistics. RESULTS: One third of the
      respondents were aware of PG, and more than half indicated interest in undergoing
      PG testing. The primary motivation provided was respondents' interest in finding
      out about their own disease risk, followed by willingness to contribute to
      scientific research. Forty-four percent were not interested in undergoing testing
      because results might be worrisome, or due to concerns about the validity of the
      results. Only a minority of respondents mentioned privacy-related concerns.
      Further, 66% were interested in undergoing clinic-based PG motivated by the
      opportunity to contribute to scientific research (78%) and 75% of all study
      participants indicated strong preferences to donate genomic data to public
      research institutions. CONCLUSION: This study indicates a relatively positive
      overall attitude towards personal genomic testing among older Swiss adults, a
      group not typically represented in surveys about personal genomics. Genomic data
      of older adults can be highly relevant to late life health and maintenance of
      quality of life. In addition they can be an invaluable source for better
      understanding of longevity, health and disease. Understanding the attitudes of
      this population towards genomic analyses, although important, remains under
      examined.

PMID- 27047755
TI  - 'Only a click away - DTC genetics for ancestry, health, love...and more: A view
      of the business and regulatory landscape'.
AB  - I provide an overview of the current state of the direct-to-consumer (DTC)
      genetic testing industry and the challenges that different types of testing pose
      for regulation. I consider the variety of services currently available. These
      range from health and ancestry tests to those for child talent, paternity, and
      infidelity. In light of the increasingly blurred lines among different categories
      of testing, I call for a broader discussion of DTC governance. I stress the
      importance of shifting our attention from the activities of the most prominent
      companies to viewing DTC genetics as an industry with a wide spectrum of services
      and raising a wide variety of issues. These issues go beyond questions of
      clinical utility and validity to those of data security, personal identity, race,
      and the nature of the family. Robust DTC testing has the power to provide
      meaningful clinical, genealogical and even forensic information to those who want
      it; in unscrupulous hands, however, it also has the power to deceive and exploit.
      I consider approaches to help ensure the former and minimize the latter. 

PMID- 27047757
TI  - Exomes for we but not for thee.

PMID- 27047758
TI  - How Geisinger made the case for an institutional duty to return genomic results
      to biobank participants.

PMID- 27047756
TI  - Ethical issues in consumer genome sequencing: Use of consumers' samples and data.
AB  - High throughput approaches such as whole genome sequencing (WGS) and whole exome
      sequencing (WES) create an unprecedented amount of data providing powerful
      resources for clinical care and research. Recently, WGS and WES services have
      been made available by commercial direct-to-consumer (DTC) companies. The DTC
      offer of genetic testing (GT) has already brought attention to potentially
      problematic issues such as the adequacy of consumers' informed consent and
      transparency of companies' research activities. In this study, we analysed the
      websites of four DTC GT companies offering WGS and/or WES with regard to their
      policies governing storage and future use of consumers' data and samples. The
      results are discussed in relation to recommendations and guiding principles such
      as the "Statement of the European Society of Human Genetics on DTC GT for health
      related purposes" (2010) and the "Framework for responsible sharing of genomic
      and health-related data" (Global Alliance for Genomics and Health, 2014). The
      analysis reveals that some companies may store and use consumers' samples or
      sequencing data for unspecified research and share the data with third parties.
      Moreover, the companies do not provide sufficient or clear information to
      consumers about this, which can undermine the validity of the consent process.
      Furthermore, while all companies state that they provide privacy safeguards for
      data and mention the limitations of these, information about the possibility of
      re-identification is lacking. Finally, although the companies that may conduct
      research do include information regarding proprietary claims and
      commercialisation of the results, it is not clear whether consumers are aware of
      the consequences of these policies. These results indicate that DTC GT companies
      still need to improve the transparency regarding handling of consumers' samples
      and data, including having an explicit and clear consent process for research
      activities. 

PMID- 27047759
TI  - An old problem in a new age: Revisiting the clinical dilemma of misattributed
      paternity.
AB  - Clinical genetics has wrestled with the problem of misattributed paternity for
      decades. While there are no clear directives on policy, surveys suggest that
      genetics professionals are inclined to avoid disclosure when possible. Changes
      associated with the increased use of genomic testing will alter the context and
      may limit the benefits of non-disclosure. Multi-site testing will preclude the
      uncertainty often associated with single-gene testing. Increased use of genetic
      testing in clinical and non-clinical settings will create new opportunities for
      the subsequent unmasking of misattributed relationships, as will the presence of
      test results in the electronic medical record. Family health history information
      will become more valuable as it is used more often and to better effect in risk
      assessment, diagnosis, treatment and reproductive decision-making. These changes
      associated with genomic testing increase the risks and decrease the benefits
      associated with the nondisclosure of misattributed paternity. For ethical and
      practical reasons, genetics professionals, and those who advise them, should
      consider a greater emphasis on the value of carefully planned disclosure. 

PMID- 27047760
TI  - Life as a numerator: Putting the person in personal genomics.

PMID- 27047761
TI  - Phenotype with a side of genotype, please: Patients, parents and priorities in
      rare genetic disease.
AB  - As the parent and caregiver of a child with an ultra-rare disease and advocate
      for others with the same condition, I discuss the importance of phenotyping in
      rare disease research. I emphasize the need for more clinical geneticists, deeper
      and more intentional integration of clinical genetics in complex patient care,
      and a greater appreciation of patients and families as an informational resource.

PMID- 27047762
TI  - Reflections on my daughter's DNA.

PMID- 27047763
TI  - Instrumentation to study myofibril mechanics from static to artificial
      simulations of cardiac cycle.
AB  - Many causes of heart muscle diseases and skeletal muscle diseases are inherited
      and caused by mutations in genes of sarcomere proteins which play either a
      structural or contractile role in the muscle cell. Tissue samples from human
      hearts with mutations can be obtained but often samples are only a few milligrams
      and it is necessary to freeze them for storage and transportation. Myofibrils are
      the fundamental contractile components of the muscle cell and retain all
      structural elements and contractile proteins performing in contractile event;
      moreover viable myofibrils can be obtained from frozen tissue.*We are describing
      a versatile technique for measuring the contractility and its Ca(2+) regulation
      in single myofibrils. The control of myofibril length, incubation medium and data
      acquisition is carried out using a digital acquisition board via computer
      software. Using computer control it is possible not only to measure contractile
      and mechanical parameters but also simulate complex protocols such as a cardiac
      cycle to vary length and medium independently.*This single myofibril force assay
      is well suited for physiological measurements. The system can be adapted to
      measure tension amplitude, rates of contraction and relaxation, Ca(2+) dependence
      of these parameters in dose-response measurements, length-dependent activation,
      stretch response, myofibril elasticity and response to simulated cardiac cycle
      length changes. Our approach provides an all-round quantitative way to measure
      myofibrils performance and to observe the effect of mutations or
      posttranslational modifications. The technique has been demonstrated by the study
      of contraction in heart with hypertrophic or dilated cardiomyopathy mutations in
      sarcomere proteins. 

PMID- 27047764
TI  - Determination of ochratoxin A in pig tissues using enzymatic digestion coupled
      with high-performance liquid chromatography with a fluorescence detector.
AB  - We present a new method for the rapid analysis of ochratoxin A (OTA) in pig
      tissues (muscle, liver and kidney) using enzymatic digestion (ED) coupled to high
      performance liquid chromatography with a fluorescence detector (HPLC-FLD). OTA
      was digested with a 1% pancreatin solution in a phosphate buffer and then cleaned
      with ethylacetate. After being evaporated to dryness and re-dissolved, the sample
      was determined using HPLC-FLD. The method was validated taking into account the
      currently permitted limit of 1 MUg/kg OTA in pork meat and derived products in
      Italy. The recovery was higher than 90%. Intra- and inter-day repeatability
      expressed as RSD were less than 7%. The LOD and LOQ were 0.001 and 0.002 MUg/kg,
      respectively. Our method is more efficient, easier, and cheaper than conventional
      clean-up procedures (liquid-liquid extraction). *The aim of the study was to
      develop and validate a quantitative HPLC-FLD method based on ED followed by a
      chromatographic analysis without any previous clean-up or concentration step for
      the detection of OTA in pig tissues.*The ED method showed a 90%+ recovery, and
      intra- and inter-day RSD less than 7%.*This method is simple, rapid, easy to use,
      and consumes low amounts of organic solvents. 

PMID- 27047765
TI  - Greater Biosynthetic Liver Dysfunction in Primary Sclerosing Cholangitis Suggests
      Co-existent or Impending Cholangiocarcinoma.
AB  - Background and Aim : Patients with primary sclerosing cholangitis (PSC) who
      develop cholangiocarcinoma (CCA) have a median survival of less than 6 months. In
      half of cases, PSC and CCA will be diagnosed either concurrently or within a year
      of one another. The aim of the present study is to demonstrate that the degree of
      biochemical liver dysfunction is associated with concomitant or impending CCA.
      Methods : We did a chart review of patients diagnosed with PSC and CCA up to 18
      months from presentation ("CCA" group) as well as patients with PSC that
      underwent transplantation with no sign of CCA in their explanted liver ("nCCA"
      group). Along with demographic data and follow-up length, we recorded their
      presenting liver function tests, including alanine and aspartate
      aminotransferases (ALT, AST), total bilirubin (TBil), alkaline phosphatase (ALP),
      international normalization ratio (INR), and serum Ca 19-9 levels. Differences
      between mean values of the two groups were analyzed with a student's t-test.
      Results : Twenty-four patients were included. The "CCA" group consisted of eight
      patients, and the "non-CCA" group had 16 patients. There was no significant
      difference between the two groups in their presenting values of ALT, ALP, or
      serum Ca 19-9. However, the "CCA" group had significantly higher levels of AST,
      TBil, and INR. Conclusion : Patients with PSC and concurrent or impending CCA
      appear to exhibit significantly greater biochemical liver dysfunction than those
      who do not develop CCA. Therefore, newly-diagnosed PSC patients presenting with
      these findings may warrant more rigorous evaluation. 

PMID- 27047766
TI  - Evaluation of Interferon Resistance in Newly Established Genotype 1b Hepatitis C
      Virus Cell Culture System.
AB  - BACKGROUND AND AIMS: The hepatitis C virus (HCV) genotype 1b is known to exhibit
      treatment resistance with respect to interferon (IFN) therapy. Substitution of
      amino acids 70 and 91 in the core region of the 1b genotype is a significant
      predictor of liver carcinogenesis and poor response to pegylated-IFN-alpha and
      ribavirin therapy. However, the molecular mechanism has not yet been clearly
      elucidated because of limitations of the HCV genotype 1b infectious model.
      Recently, the TPF1-M170T HCV genotype 1b cell culture system was established, in
      which the clone successfully replicates and infects Huh-7-derived Huh7-ALS32.50
      cells. Therefore, the purpose of this study was to compare IFN resistance in
      various HCV clones using this system. METHODS: HCV core amino acid substitutions
      R70Q and L91M were introduced to the TPF1-M170T clone and then transfected into
      Huh7-ALS32.50 cells. To evaluate the production of each virus, intracellular HCV
      core antigens were measured. RESULTS were confirmed with Western blot analysis
      using anti-NS5A antibodies, and IFN sensitivity was subsequently measured.
      RESULTS: Each clone was transfected successfully compared with JFH-1, with a
      significant difference in intracellular HCV core antigen (p < 0.05), an indicator
      of continuous HCV replication. Among all clones, L91M showed the highest increase
      in the HCV core antigen and HCV protein. There was no significant resistance
      against IFN treatment in core substitutions; however, IFN sensitivity was
      significantly different between the wildtype core and JFH-1 (p < 0.05).
      CONCLUSIONS: A novel genotype 1b HCV cell culture was constructed with core amino
      acid substitutions, which demonstrated IFN resistance of genotype 1b. This system
      will be useful for future analyses into the mechanisms of HCV genotype 1b
      treatment.

PMID- 27047767
TI  - Overestimate of Fibrosis by FIBROSpect(r) II in African Americans Complicates the
      Management of their Chronic Hepatitis C.
AB  - BACKGROUND: Evaluation of advanced fibrosis in patients with hepatitis C virus
      (HCV) infection is used to facilitate decisions on treatment strategy and to
      initiate additional screening measures. Unfortunately, most studies have
      predominately Caucasian (Cau) patients and may not be as relevant for African
      Americans (AA). AIMS: This study specifically addresses the issue of defining
      minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis
      C (CHC) using noninvasive assays. METHODS: All patients (n = 319) seen between 1
      January 2008 and 30 June 2013 for whom a FibroSpect II(r) (FSII) assay was
      performed and had data for calculation of aspartate aminotransferase (AST)
      platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the
      medical records. RESULTS: When liver biopsy score and FSII assay results for the
      AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores
      (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The
      AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with
      either APRI (7% false positive) or FIB-4 (10% false positive) improved the false
      positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the
      sensitivity for significant fibrosis. CONCLUSIONS: The FSII assay overestimates
      fibrosis in AA and should be used with caution since these patients may not have
      significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay,
      minimal fibrosis in AA can be defined without subjecting the patients to a
      subsequent biopsy.

PMID- 27047768
TI  - Routine Laboratory Blood Tests May Diagnose Significant Fibrosis in Liver
      Transplant Recipients with Chronic Hepatitis C: A 10 Year Experience.
AB  - BACKGROUND AND AIMS: The aims of our study were to determine whether routine
      blood tests, the aspartate aminotransferase (AST) to Platelet Ratio Index (APRI)
      and Fibrosis 4 (Fib-4) scores, were associated with advanced fibrosis and to
      create a novel model in liver transplant recipients with chronic hepatitis C
      virus (HCV). METHODS: We performed a cross sectional study of patients at The
      University of California at Los Angeles (UCLA) Medical Center who underwent liver
      transplantation for HCV. We used linear mixed effects models to analyze
      association between fibrosis severity and individual biochemical markers and
      mixed effects logistic regression to construct diagnostic models for advanced
      fibrosis (METAVIR F3-4). Cross-validation was used to estimate a receiving
      operator characteristic (ROC) curve for the prediction models and to estimate the
      area under the curve (AUC). RESULTS: The mean (+/- standard deviation [SD]) age
      of our cohort was 55 (+/-7.7) years, and almost three quarter were male. The mean
      (+/-SD) time from transplant to liver biopsy was 19.9 (+/-17.1) months. The mean
      (+/-SD) APRI and Fib-4 scores were 3 (+/-12) and 7 (+/-14), respectively.
      Increased fibrosis was associated with lower platelet count and alanine
      aminotransferase (ALT) values and higher total bilirubin and Fib-4 scores. We
      developed a model that takes into account age, gender, platelet count, ALT, and
      total bilirubin, and this model outperformed APRI and Fib-4 with an AUC of 0.68
      (p < 0.001). CONCLUSIONS: Our novel prediction model diagnosed the presence of
      advanced fibrosis more reliably than APRI and Fib-4 scores. This noninvasive
      calculation may be used clinically to identify liver transplant recipients with
      HCV with significant liver damage.

PMID- 27047769
TI  - Association of Overt Diabetes Mellitus with the Non-CC but not the CC Genotype of
      Interleukin-28B in Hepatitis C Virus Infected Patients.
AB  - BACKGROUND: Interleukin-28B (IL-28B) polymorphism is an important predictor for
      hepatitis C virus (HCV) treatment response. Whether IL-28b genotypes also
      influence other nontreatment related clinical parameters is unclear. METHODS:
      Patients with HCV-related chronic liver diseases who attended our department
      during 2012-2014 were retrospectively analyzed. The single nucleotide
      polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical
      parameters. We also compared these parameters in patients with and without overt
      diabetes to identify possible associations. RESULTS: A total of 115 patients were
      included (median age 48, range 15-76 years; 70% males). Overall, 43/115 (37%)
      patients had chronic hepatitis, while the remaining 72/115 (63%) had cirrhosis.
      The most common IL-28B genotype was CC, which was found in 53% of patients
      (61/115), while the remaining 47% were nonCC [CT 42% (48/115) and TT 5% (6/115)].
      Clinical and laboratory parameters like Hb, white blood cell (WBC), platelets,
      bilirubin, transaminases, and albumin were similar in the CC and nonCC genotypes.
      Overt diabetes mellitus was present in 22% (25/115) of patients. Patients with
      nonCC genotype had significantly higher prevalence of overt diabetes mellitus
      than patients with CC genotype (31% [17/54] versus 13% [8/61]; p < 0.05). When
      parameters were compared in patients with and without overt diabetes mellitus,
      only IL-28B and age were significantly associated with overt diabetes mellitus (p
      < 0.05). CONCLUSION: In HCV patients, overt diabetes mellitus was more commonly
      associated with the nonCC genotype of IL-28B than the CC genotype. Carriers of
      the T-allele of SNP rs12979860 were more likely to have insulin resistance than
      CC homozygotes, and this finding may explain the higher prevalence of diabetes in
      non-CC genotypes. Thus, an IL-28B test may be useful in patients of HCV in order
      to determine their likelihood of developing diabetes mellitus.

PMID- 27047770
TI  - Curing Hepatitis C in Liver Transplant Recipients Is Associated with Changes in
      Immunosuppressant Use.
AB  - BACKGROUND AND AIMS: All-oral interferon-free antivirals are highly effective in
      treating recurrent hepatitis C (HCV) infection in liver transplant (LT)
      recipients. The aim of the study was to assess immunosuppression needs after
      achieving a sustained viral response (SVR). METHODS: We compared
      immunosuppression needs before and after achieving a SVR in adult LT recipients
      treated for recurrent HCV infection with all-oral direct acting agents. RESULTS:
      We identified 52 liver LT treated recipients who achieved a SVR. The median (25th
      and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most
      recipients received tacrolimus (TAC) for their immunosuppressant regimen. After
      achieving SVR, there was no statistically significant difference in daily dose of
      TAC unadjusted per weight (p > 0.05). However, there was a statistically
      significant decrease in daily dose of TAC adjusted per weight, serum levels of
      TAC, and the product of glomerular filtration rate and TAC. No statistically
      significant differences in cyclosporine unadjusted/adjusted per weight daily dose
      or serum levels were noted. CONCLUSIONS: Immunosuppression needs were increased
      for those patients treated with TAC but not cyclosporine. LT recipients
      prescribed TAC require close monitoring after treatment completion to avoid
      potential risk of acute rejection.

PMID- 27047771
TI  - Hepatic Echinococcal Cysts: A Review.
AB  - Cystic echinococcosis (CE) is a widely endemic helminthic disease caused by
      infection with metacestodes (larval stage) of the Echinococcus granulosus
      tapeworm. E. granulosus are common parasites in certain parts of the world, and
      are present on every continent with the exception of Antarctica. As a result, a
      large number of people are affected by CE. The increased emigration of
      populations from endemic areas where prevalence rates are as high as 5-10% and
      the relatively quiescent clinical course of CE pose challenges for accurate and
      timely diagnoses. Upon infection with CE, cyst formation mainly occurs in the
      liver (70%). Diagnosis involves serum serologic testing for antibodies against
      hydatid antigens, but preferably with imaging by ultrasound or CT/MRI. Treatment
      methods include chemotherapy with benzimidazole carbamates and/or surgical
      approaches, including percutaneous aspiration injection and reaspiration. The
      success of these methods is influenced by the stage and location of hepatic
      cysts. However, CE can be clinically silent, and has a high risk for recurrence.
      It is important to consider the echinococcal parasite in the differential
      diagnosis of liver cystic lesions, especially in patients of foreign origin, and
      to perform appropriate long-term follow-ups. The aim of this review is to
      highlight the epidemiology, natural history, diagnostic methods, and treatment of
      liver disease caused by E. granulosus. 

PMID- 27047772
TI  - Hepatopulmonary Syndrome and Liver Transplantation: A Recent Review of the
      Literature.
AB  - A severe and common pulmonary vascular complication of liver disease is
      hepatopulmonary syndrome (HPS). It is a triad of liver dysfunction and/or portal
      hypertension, intrapulmonary vascular dilatations, and increased alveolar
      arterial oxygen gradient. Prevalence varies according to various study groups
      from 4%-47%. While the most common presenting symptom of HPS is dyspnea, it is
      usually asymptomatic, and thus all liver transplant candidates should be screened
      for its presence. Pulse oximetry is a useful screening method, but arterial blood
      gas examination is the gold standard. If there is an abnormal P (A-a)O2 gradient,
      microbubble transthoracic echocardiography should be done for diagnosis. Outcome
      is unpredictable, and there is currently no effective medical therapy. The only
      effective therapy is considered to be liver transplantation. Complete resolution
      of HPS after liver transplantation is seen within a year in most HPS patients. 

PMID- 27047773
TI  - Prevention and Treatment of Recurrent Hepatitis B after Liver Transplantation.
AB  - Chronic hepatitis B is a global health problem that leads to development of
      various complications, such as cirrhosis, liver cancer, and liver failure
      requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post
      liver transplantation is a major cause of allograft dysfunction, cirrhosis of the
      allograft, and graft failure. Patients with high viral load at the time of
      transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a
      history of anti-viral drug resistance are considered as high-risk for recurrent
      HBV post-liver transplantation, while patients with low viral load, including
      HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co
      infection are considered to be at low-risk for recurrent HBV post-liver
      transplantation. Antivirals for patients awaiting liver transplantation(LT) cause
      suppression of HBV replication and reduce the risk of recurrent HBV infection of
      the allograft and, therefore, all HBV patients with decompensated cirrhosis
      should be treated with potent antivirals with high genetic barrier to resistance
      (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver
      transplantation recurrence should be done using a combination of hepatitis B
      immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low
      dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals
      can still be considered in patients at low risk of recurrence. Even, marginal
      grafts from anti-HBc positive donors can be safely used in hepatitis B surface
      antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti
      hepatitis B surface (HBs) positive recipients. In this article, we aim to review
      the mechanisms and risk factors of HBV recurrence post-LT in addition to the
      various treatment strategies proposed for the prevention of recurrent HBV
      infection. 

PMID- 27047775
TI  - New technology in breast reconstruction.

PMID- 27047776
TI  - The microvascular anastomotic coupler for venous anastomoses in free flap breast
      reconstruction improves outcomes.
AB  - BACKGROUND: Venous couplers are ubiquitous around the world and are a useful tool
      for the reconstructive microsurgeon. A systematic review of coupler performance
      studies demonstrated a thrombosis rate range of 0% to 3%, whilst the average time
      of using the device is 5 minutes. There is sparse published data on cost analysis
      and the impact of operator experience on the anastomotic coupler device success.
      Improvements in outcomes other than time benefits have also not been shown. This
      study aims to address these deficiencies in the literature. METHODS: A
      retrospective clinical study was undertaken, aiming to compare equivalent groups
      of patients that had free flap surgery with venous micro-anastomoses with those
      that had sutured anastomoses. The cohort comprised all patients undergoing
      microsurgical breast reconstruction at the St Andrew's Centre for Plastic Surgery
      & Burns from January 2009 to December 2014. RESULTS: Between January 2010 to
      December 2014, 1,064 patients underwent 1,206 free flap breast reconstructions.
      The average age of patients was 50 years. Seventy percent of patients underwent
      mastectomy and immediate reconstruction during this period with the remaining 30%
      having a delayed reconstruction. The 1,206 free flaps comprised of 83 transverse
      myocutaneous gracilis (TMG) flaps, and 1,123 deep inferior epigastric artery
      perforator (DIEP) flaps. In total the coupler was used in 319 flaps, 26% of the
      cohort. There was a statistically significant clinical benefit in using the
      anastomotic coupler for venous anastomosis. Overall, the return to theatre rate
      was 12.69% whilst the overall flap loss rate was 0.75%. The overall coupler
      failure rate was significantly less at 1.4% whilst sutured vein failure rate was
      3.57% (P=0.001). CONCLUSIONS: The anastomotic coupler for venous anastomosis in
      free flap surgery is associated with reduced operating times, reduced take-backs
      to theatre and cost benefits. This is the first study to demonstrate clear
      clinical benefits to anastomotic couplers, and suggests that these may be the
      gold standard for venous microanastomosis. With increasing experience with their
      use and technological advances, these outcomes may continue to improve.

PMID- 27047774
TI  - Hepatitis C Virus, Insulin Resistance, and Steatosis.
AB  - Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide.
      Liver steatosis is a common finding in many hepatic and extrahepatic disorders,
      the most common being metabolic syndrome (MS). Over time, it has been shown that
      the frequent coexistence of these two conditions is not coincidental, since many
      epidemiological, clinical, and experimental studies have indicated HCV to be
      strongly associated with liver steatosis and numerous metabolic derangements.
      Here, we present an overview of publications that provide clinical evidence of
      the metabolic effects of HCV and summarize the available data on the pathogenetic
      mechanisms of this association. It has been shown that HCV infection can induce
      insulin resistance (IR) in the liver and peripheral tissues through multiple
      mechanisms. Substantial research has suggested that HCV interferes with insulin
      signaling both directly and indirectly, inducing the production of several
      proinflammatory cytokines. HCV replication, assembly, and release from
      hepatocytes require close interactions with lipid droplets and host lipoproteins.
      This modulation of lipid metabolism in host cells can induce hepatic steatosis,
      which is more pronounced in patients with HCV genotype 3. The risk of steatosis
      depends on several viral factors (including genotype, viral load, and gene
      mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic
      predisposition, medication use, and alcohol consumption). HCV-related IR and
      steatosis have been shown to have a remarkable clinical impact on the prognosis
      of HCV infection and quality of life, due to their association with resistance to
      antiviral therapy, progression of hepatic fibrosis, and development of
      hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes
      in lipid and iron metabolism lead to glucose intolerance, arterial hypertension,
      hyperuricemia, and atherosclerosis, resulting in increased cardiovascular
      mortality. 

PMID- 27047777
TI  - Preoperative computed tomography angiography for planning DIEP flap breast
      reconstruction reduces operative time and overall complications.
AB  - BACKGROUND: The approach and operative techniques associated with breast
      reconstruction have steadily been refined since its inception, with abdominal
      perforator-based flaps becoming the gold standard reconstructive option for women
      undergoing breast cancer surgery. The current study comprises a cohort of 632
      patients, in whom specific operative times are recorded by a blinded observer,
      and aims to address the potential benefits seen with the use of computer
      tomography (CT) scanning preoperatively on operative outcomes, complications and
      surgical times. METHODS: A prospectively recorded, retrospective review was
      undertaken of patients undergoing autologous breast reconstruction with a DIEP
      flap at the St Andrews Centre over a 4-year period from 2010 to 2014. Computed
      tomography angiography (CTA) scanning of patients began in September 2012 and
      thus 2 time periods were compared: 2 years prior to the use of CTA scans and 2
      years afterwards. For all patients, key variables were collected including
      patient demographics, operative times, flap harvest time, pedicle length, surgeon
      experience and complications. RESULTS: In group 1, comprising patients within the
      period prior to CTA scans, 265 patients underwent 312 flaps; whilst in group 2,
      the immediately following 2 years, 275 patients had 320 flaps. The use of
      preoperative CTA scans demonstrated a significant reduction in flap harvest time
      of 13 minutes (P<0.013). This significant time saving was seen in all flap
      modifications: unilateral, bilateral and bipedicled DIEP flaps. The greatest time
      saving was seen in bipedicle flaps, with a 35-minute time saving. The return to
      theatre rate significantly dropped from 11.2% to 6.9% following the use of CTA
      scans, but there was no difference in the total failure rate. CONCLUSIONS: The
      study has demonstrated both a benefit to flap harvest time as well as overall
      operative times when using preoperative CTA. The use of CTA was associated with a
      significant reduction in complications requiring a return to theatre in the
      immediate postoperative period. Modern scanners and techniques can reduce the
      level of ionising radiation, facilitating patients being able to benefit from the
      advantages that this preoperative planning can convey.

PMID- 27047778
TI  - Comparative study of software techniques for 3D mapping of perforators in deep
      inferior epigastric artery perforator flap planning.
AB  - BACKGROUND: Computed tomographic (CT) angiography (CTA) is widely considered the
      gold standard imaging modality for preoperative planning autologous breast
      reconstruction with deep inferior epigastric artery (DIEA) perforator (DIEP)
      flap. Improved anatomical understanding from CTA has translated to enhanced
      clinical outcomes. To achieve this, the use of appropriate CT hardware and
      software is vital. Various CT scanners and contrast materials have been
      demonstrated to consistently produce adequate scan data. However, the
      availability of affordable and easily accessible imaging software capable of
      generating 3D volume-rendered perforator images to clinically useful quality has
      been lacking. Osirix (Pixmeo, Geneva, Switzerland) is a free, readily available
      medical image processing software that shows promise. We have previously
      demonstrated in a case report the usefulness of Osirix in localizing perforators
      and their course. METHODS: In the current case series of 50 consecutive CTA
      scans, we compare the accuracy of Osirix to a commonly used proprietary 3D
      imaging software, Siemens Syngo InSpace 4D (Siemens, Erlangen, Germany), in
      identifying perforator number and location. Moreover, we compared both programs
      to intraoperative findings. RESULTS: We report a high rate of concordance with
      Osirix and Siemens Syngo InSpace 4D (99.6%). Both programs correlated closely
      with operative findings (92.2%). Most of the discrepancies were found in the
      lateral row perforators (90%). CONCLUSIONS: In the current study, we report the
      accuracy of Osirix that is comparable to Siemens Syngo InSpace 4D, a proprietary
      software, in mapping perforators. However, it provides an added advantage of
      being free, easy-to-use, portable, and potentially a superior quality of 3D
      reconstructed image.

PMID- 27047779
TI  - Three routine free flaps per day in a single operating theatre: principles of a
      process mapping approach to improving surgical efficiency.
AB  - BACKGROUND: Breast reconstruction is a multi-stage process, involving many
      individual procedures and many healthcare professionals which take the patient
      through from diagnosis of breast cancer to the completion of cancer treatment and
      ultimate breast reconstruction. With an experience of over 3,000 autologous
      breast reconstructions, we have refined both our surgical technique and overall
      approach to breast reconstruction to improve the efficiency in free flap based
      breast reconstruction surgery. METHODS: Through a process mapping approach
      similar to that employed by large-scale industry, we have broken down free flap
      based breast reconstruction into multiple smaller processes. By looking at
      various steps as a simple component of the whole, we have improved our theatre
      efficiency to maximize patient throughput and improve our outcomes for breast
      reconstruction patients. RESULTS: Since beginning free flap breast reconstruction
      surgery, we have improved overall efficiency by applying a process mapping
      approach. In our early experience, we undertook a single patient undergoing
      breast reconstruction with a free flap per theatre list, moving to two patients
      having breast reconstruction, and now carry out three free flap based
      reconstructions in a single theatre per day as a routine. Specific times are
      demonstrated, with no increased complication rate. CONCLUSIONS: Through clearly
      defined processes, operative efficiency in autologous breast reconstruction can
      achieve three free flaps per day in a single theatre.

PMID- 27047780
TI  - Stacked and bipedicled abdominal free flaps for breast reconstruction:
      considerations for shaping.
AB  - BACKGROUND: Stacked and bipedicled abdominal flaps are useful in women who
      require a large breast reconstruction but have relative paucity of abdominal
      tissue. A new classification system is described to assist the surgeon in
      achieving the best possible aesthetic outcome. METHODS: A retrospective review of
      25 consecutive stacked and/or bipedicled deep inferior epigastric perforator
      (DIEP) flap reconstructions was assessed from 2009 to 2014. Demographic data and
      key variables were prospectively collected in our breast reconstruction database
      and an aesthetic classification devised. There are four main subtypes, (I)
      folded; (II) divided; (III) coned; and (IV) divided and folded. Each of these
      subtypes can be moulded in a symmetrically or asymmetrically fashion depending on
      the contralateral breast shape together with distribution and consistency of fat
      within the abdominal flap. RESULTS: Of the 25 patients, three-quarter were
      immediate reconstruction, with an average age of 48 years and a median follow-up
      of 2 years 10 months. Just over half the patients (57%) had bipedicle flaps with
      two recipient donor vessels with the remaining 43% had stacked flaps. The most
      common recipient sites are the thoracodorsal vessels (62%) and intercostal
      perforators (26%). The average abdominal pannus weight was 610 grams (SD: 320
      grams), with a hemi-abdominal weight of 305 grams. Two patients had haematomas,
      of which one lost their reconstruction. Another patient had a venous congestion
      flap which was salvaged. CONCLUSIONS: Bipedicled or stacked abdominal flaps allow
      the all four zones of the abdominal tissue to be used in unilateral breast
      reconstruction. The approach of tailoring the abdominal flaps to match the
      contralateral breast reconstruction is largely an art form. The paper aims to
      bring some meaningful system to aid the surgeon to achieve the best possible
      outcome with the components presented to them.

PMID- 27047781
TI  - Clinical applications of dynamic infrared thermography in plastic surgery: a
      systematic review.
AB  - BACKGROUND: Infrared thermography (IRT) has become an increasingly utilized
      adjunct to more expensive and/or invasive investigations in a range of surgical
      fields, no more so than in plastic surgery. The combination of functional
      assessment, flow characteristics and anatomical localization has led to
      increasing applications of this technology. This article aims to perform a
      systematic review of the clinical applications of IRT in plastic surgery.
      METHODS: A systematic literature search using the keywords 'IRT' and 'dynamic
      infrared thermography (DIRT)' has been accomplished. A total of 147 papers were
      extracted from various medical databases, of which 34 articles were subjected to
      a full read by two independent reviewers, to ensure the papers satisfied the
      inclusion and exclusion criteria. Studies focusing on the use of IRT in breast
      cancer diagnosis were excluded. RESULTS: A systematic review of 29 publications
      demonstrated the clinical applications of IRT in plastic surgery today. They
      include preoperative planning of perforators for free flaps, post operative
      monitoring of free flaps, use of IRT as an adjunct in burns depth analysis, in
      assessment of response to treatment in hemangioma and as a diagnostic test for
      cutaneous melanoma and carpal tunnel syndrome (CTS). CONCLUSIONS: Modern infrared
      imaging technology with improved standardization protocols is now a credible,
      useful non-invasive tool in clinical practice.

PMID- 27047783
TI  - Modern use of smartphone applications in the perioperative management in
      microsurgical breast reconstruction.
AB  - BACKGROUND: Advances in mobile telecommunication, improved mobile internet and
      affordability have led to a significant increase in smartphone use within
      medicine. The capability of instant messaging, photography, videography, word
      processing, drawing and internet access allow significant potential in this small
      portable device. Smartphone use within medicine has grown tremendously worldwide
      given its affordability, improved internet and capabilities. METHODS: We have
      searched for apps specifically helpful in the perioperative care of microsurgical
      breast reconstructive patients. RESULTS: The useful apps have been subdivided:
      (I) communication apps-multimedia messaging, WhatsApp, PicSafeMedi: allow
      efficient communication via text, picture and video messages leading to earlier
      assessment and definitive management of free flaps; (II) storage apps-Notability,
      Elogbook: electronic storage of patient notes and logbooks of case which can be
      shared with others if required; (III) educational apps-FlapApp, Touch Surgery,
      PubMed on tap: step by step guides to surgical procedures to aid learning and
      medical journal database; (IV) flap monitoring app-SilpaRamanitor: free flap
      monitoring app based on photographic analysis for earlier detection of
      compromised flaps. CONCLUSIONS: There has been remarkable growth in smartphones
      use among surgeons. Apps are being developed for every conceivable use. The
      future will be in wearable smart devices that allow continuous monitoring with
      the potential to instigate change should deviations from the norm occur. The
      smart watch is the start of this digital revolution.

PMID- 27047782
TI  - Indocyanine green-based fluorescent angiography in breast reconstruction.
AB  - BACKGROUND: Fluorescent angiography (FA) has been useful for assessing blood flow
      and assessing tissue perfusion in ophthalmology and other surgical disciplines
      for decades. In plastic surgery, indocyanine green (ICG) dye-based FA is a
      relatively novel imaging technology with high potential in various applications.
      We review the various FA detector systems currently available and critically
      appraise its utility in breast reconstruction. METHODS: A review of the published
      English literature dating from 1950 to 2015 using databases, such as PubMed,
      Medline, Web of Science, and EMBASE was undertaken. RESULTS: In comparison to the
      old fluorescein dye, ICG has a superior side effect profile and can be accurately
      detected by various commercial devices, such as SPY Elite (Novadaq, Canada),
      FLARE (Curadel LLC, USA), PDE-Neo (Hamamatsu Photonics, Japan), Fluobeam 800
      (Fluoptics, France), and IC-View (Pulsion Medical Systems AG, Germany). In breast
      reconstruction, ICG has established as a safer, more accurate tracer agent, in
      lieu of the traditional blue dyes, for detection of sentinel lymph nodes with
      radioactive isotopes ((99m)-Technetium). In prosthesis-based breast
      reconstruction, intraoperative assessment of the mastectomy skin flap to guide
      excision of hypoperfused areas translates to improved clinical outcomes.
      Similarly, in autologous breast reconstructions, FA can be utilized to detect
      poorly perfused areas of the free flap, evaluate microvascular anastomosis for
      patency, and assess SIEA vascular territory for use as an alternative free flap
      with minimal donor site morbidity. CONCLUSIONS: ICG-based FA is a novel, useful
      tool for various applications in breast reconstruction. More studies with higher
      level of evidence are currently lacking to validate this technology.

PMID- 27047784
TI  - Alloplastic adjuncts in breast reconstruction.
AB  - BACKGROUND: There has been an increasing role of acellular dermal matrices (ADMs)
      and synthetic meshes in both single- and two-stage implant/expander breast
      reconstruction. Numerous alloplastic adjuncts exist, and these vary in material
      type, processing, storage, surgical preparation, level of sterility, available
      sizes and cost. However, there is little published data on most, posing a
      significant challenge to the reconstructive surgeon trying to compare and select
      the most suitable product. The aims of this systematic review were to identify,
      summarize and evaluate the outcomes of studies describing the use of alloplastic
      adjuncts for post-mastectomy breast reconstruction. The secondary aims were to
      determine their cost-effectiveness and analyze outcomes in patients who also
      underwent radiotherapy. METHODS: Using the PRSIMA 2009 statement, a systematic
      review was conducted to find articles reporting on the outcomes on the use of
      alloplastic adjuncts in post-mastectomy breast reconstruction. Multiple databases
      were searched independently by three authors (Cabalag MS, Miller GS and Chae MP),
      including: Ovid MEDLINE (1950 to present), Embase (1980 to 2015), PubMed and
      Cochrane Database of Systematic Reviews. RESULTS: Current published literature on
      available alloplastic adjuncts are predominantly centered on ADMs, both
      allogeneic and xenogeneic, with few outcome studies available for synthetic
      meshes. Outcomes on the 89 articles, which met the inclusion criteria, were
      summarized and analyzed. The reported outcomes on alloplastic adjunct-assisted
      breast reconstruction were varied, with most data available on the use of ADMs,
      particularly AlloDerm((r)) (LifeCell, Branchburg, New Jersey, USA). The use of
      ADMs in single-stage direct-to-implant breast reconstruction resulted in lower
      complication rates (infection, seroma, implant loss and late revision), and was
      more cost effective when compared to non-ADM, two-stage reconstruction. The
      majority of studies demonstrated inferior outcomes in ADM assisted, two-stage
      expander-to-implant reconstruction compared to non-ADM use. Multiple studies
      suggest that the use of ADMs results in a reduction of capsular contracture
      rates. Additionally, the reported beneficial effects of ADM use in irradiated
      tissue were varied. CONCLUSIONS: ADM assisted two-stage breast reconstruction was
      associated with inferior outcomes when compared to non-ADM use. However,
      alloplastic adjuncts may have a role in single stage, direct-to-implant breast
      reconstruction. Published evidence comparing the long-term outcomes between the
      different types of adjuncts is lacking, and further level one studies are
      required to identify the ideal product.

PMID- 27047785
TI  - Prosthetic breast reconstruction: indications and update.
AB  - BACKGROUND: Despite 82% of patients reporting psychosocial improvement following
      breast reconstruction, only 33% patients choose to undergo surgery. Implant
      reconstruction outnumbers autologous reconstruction in many centres. METHODS: A
      systematic review of the literature was undertaken. Inclusion required: (I) Meta
      analyses or review articles; (II) adult patients aged 18 years or over undergoing
      alloplastic breast reconstruction; (III) studies including outcome measures; (IV)
      case series with more than 10 patients; (V) English language; and (VI)
      publication after 1(st) January, 2000. RESULTS: After full text review, analysis
      and data extraction was conducted for a total of 63 articles. Definitive
      reconstruction with an implant can be immediate or delayed. Older patients have
      similar or even lower complication rates to younger patients. Complications
      include capsular contracture, hematoma and infection. Obesity, smoking, large
      breasts, diabetes and higher grade tumors are associated with increased risk of
      wound problems and reconstructive failure. Silicone implant patients have higher
      capsular contracture rates but have higher physical and psychosocial function.
      There were no associations made between silicone implants and cancer or systemic
      disease. There were no differences in outcomes or complications between round and
      shaped implants. Textured implants have a lower risk of capsular contracture than
      smooth implants. Smooth implants are more likely to be displaced as well as
      having higher rates of infection. Immediate breast reconstruction (IBR) gives the
      best aesthetic outcome if radiotherapy is not required but has a higher rate of
      capsular contracture and implant failure. Delayed-immediate reconstruction
      patients can achieve similar aesthetic results to IBR whilst preserving the
      breast skin if radiotherapy is required. Delayed breast reconstruction (DBR)
      patients have fewer complications than IBR patients. CONCLUSIONS: Implant
      reconstruction is a safe and popular mode of post-mastectomy reconstruction.
      Evidence exists for the settings in which complications are more likely, and we
      can now more reliably predict outcomes of reconstruction on an individual basis
      and assess patient suitability.

PMID- 27047786
TI  - Lymphatic mapping and preoperative imaging in the management of post-mastectomy
      lymphoedema.
AB  - Early detection and diagnosis of upper extremity lymphoedema in patients after
      mastectomy and axillary lymph node clearance is important in order to treat
      disease before it is too advanced to achieve favourable outcomes. Patients with
      disease refractory to conservative management can be efficiently assessed for
      diagnosis and surgical intervention using advanced lymphatic imaging techniques.
      The current paper highlights the more readily available of these:
      lymphoscintigraphy, indocyanine green (ICG) lymphangiography and
      immunofluorescence, magnetic resonance lymphangiography (MRL) and computed
      tomographic lymphangiography in combination or individually. With such
      techniques, both diagnosis and treatment of lymphoedema has become more readily
      achieved, with lymphatico-venous and lymphatico-lymphatic anastomosis, and lymph
      node transfer now increasingly common undertakings. 

PMID- 27047787
TI  - Magnetic resonance angiography in perforator flap breast reconstruction.
AB  - Magnetic resonance angiography (MRA) is an extremely useful preoperative imaging
      test for evaluation of the vasculature of donor tissue to be used in autologous
      breast reconstruction. MRA has sufficient spacial resolution to reliably
      visualize 1 mm perforating vessels and to accurately locate vessels in reference
      to a patient's anatomic landmarks without exposing patients to ionizing radiation
      or iodinated contrast. The use of a blood pool contrast agent and the lack of
      radiation exposure allow multiple studies of multiple anatomic regions in one
      examination. The following article is a detailed description of our MRA protocol
      developed with our radiologists with examples that illustrate the utility of MRA
      in perforator flap breast reconstruction. 

PMID- 27047788
TI  - Breast volumetric analysis for aesthetic planning in breast reconstruction: a
      literature review of techniques.
AB  - BACKGROUND: Accurate volumetric analysis is an essential component of
      preoperative planning in both reconstructive and aesthetic breast procedures
      towards achieving symmetrization and patient-satisfactory outcome. Numerous
      comparative studies and reviews of individual techniques have been reported.
      However, a unifying review of all techniques comparing their accuracy,
      reliability, and practicality has been lacking. METHODS: A review of the
      published English literature dating from 1950 to 2015 using databases, such as
      PubMed, Medline, Web of Science, and EMBASE, was undertaken. RESULTS: Since
      Bouman's first description of water displacement method, a range of volumetric
      assessment techniques have been described: thermoplastic casting, direct
      anthropomorphic measurement, two-dimensional (2D) imaging, and computed
      tomography (CT)/magnetic resonance imaging (MRI) scans. However, most have been
      unreliable, difficult to execute and demonstrate limited practicability.
      Introduction of 3D surface imaging has revolutionized the field due to its ease
      of use, fast speed, accuracy, and reliability. However, its widespread use has
      been limited by its high cost and lack of high level of evidence. Recent
      developments have unveiled the first web-based 3D surface imaging program, 4D
      imaging, and 3D printing. CONCLUSIONS: Despite its importance, an accurate,
      reliable, and simple breast volumetric analysis tool has been elusive until the
      introduction of 3D surface imaging technology. However, its high cost has limited
      its wide usage. Novel adjunct technologies, such as web-based 3D surface imaging
      program, 4D imaging, and 3D printing, appear promising.

PMID- 27047790
TI  - Advances in imaging technologies for planning breast reconstruction.
AB  - The role and choice of preoperative imaging for planning in breast reconstruction
      is still a disputed topic in the reconstructive community, with varying opinion
      on the necessity, the ideal imaging modality, costs and impact on patient
      outcomes. Since the advent of perforator flaps their use in microsurgical breast
      reconstruction has grown. Perforator based flaps afford lower donor morbidity by
      sparing the underlying muscle provide durable results, superior cosmesis to
      create a natural looking new breast, and are preferred in the context of
      radiation therapy. However these surgeries are complex; more technically
      challenging that implant based reconstruction, and leaves little room for error.
      The role of imaging in breast reconstruction can assist the surgeon in exploring
      or confirming flap choices based on donor site characteristics and presence of
      suitable perforators. Vascular anatomical studies in the lab have provided the
      surgeon a foundation of knowledge on location and vascular territories of
      individual perforators to improve our understanding for flap design and safe flap
      harvest. The creation of a presurgical map in patients can highlight any abnormal
      or individual anatomical variance to optimize flap design, intraoperative
      decision-making and execution of flap harvest with greater predictability and
      efficiency. This article highlights the role and techniques for preoperative
      planning using the newer technologies that have been adopted in reconstructive
      clinical practice: computed tomographic angiography (CTA), magnetic resonance
      angiography (MRA), laser-assisted indocyanine green fluorescence angiography (LA
      ICGFA) and dynamic infrared thermography (DIRT). The primary focus of this paper
      is on the application of CTA and MRA imaging modalities. 

PMID- 27047789
TI  - Adipose regeneration and implications for breast reconstruction: update and the
      future.
AB  - The evolution of breast reconstruction and management of breast cancer has
      evolved significantly since the earliest descriptions in the Edwin Smith Papyrus
      (3,000 BC). The development of surgical and scientific expertise has changed the
      way that women are managed, and plastic surgeons are now able to offer a wide
      range of reconstructive options to suit individual needs. Beyond the gold
      standard autologous flap based reconstructions, regenerative therapies promise
      the elimination of donor site morbidity whilst providing equivalent aesthetic and
      functional outcomes. Future research aims to address questions regarding ideal
      cell source, optimisation of scaffold composition and interaction of de novo
      adipose tissue in the microenvironment of breast cancer. 

PMID- 27047791
TI  - Increasing options in autologous microsurgical breast reconstruction: four free
      flaps for 'stacked' bilateral breast reconstruction.
AB  - For autologous breast reconstruction, there are cases where one free flap cannot
      provide the volume of tissue required, and the concept of 'stacked' bilateral
      deep inferior epigastric artery (DIEP) flaps was developed, in which hemi
      abdominal flaps are raised on each deep inferior epigastric artery (DIEA), and
      both flaps transferred to the chest. In cases of bilateral breast reconstruction,
      stacked flaps may be required to achieve volume replacement, however options are
      not described. We demonstrate the use of stacked free flaps for bilateral breast
      reconstruction, using one DIEP flap stacked with one transverse upper gracilis
      (TUG) flap for each side. A 49-year-old woman, with BRCA1 mutation, presented for
      risk reduction mastectomies. Flap design was planned to achieve maximal
      projection and primary nipple reconstruction. This was able to be achieved by
      using the DIEP flap de-epithelialised and completely buried, with the flap
      orientated with the pedicle on its superficial surface, and the TUG flap lying
      superficially with its skin paddle used for nipple reconstruction and able to be
      monitored clinically. There were no flap or donor related complications and good
      aesthetic outcomes were achieved. This technique offers a further option in
      microsurgical breast reconstruction for patients in whom there is a paucity of
      abdominal tissue for reconstruction. 

PMID- 27047792
TI  - Effect of Hydroalcoholic Leaves Extract of Rhus Coriaria on Pain in Male Rats.
AB  - BACKGROUND: The drive toward the use of medicinal plants has been increasing in
      recent years. They have few side effects and a large variety of efficient
      components. OBJECTIVES: This study was designed to investigate the analgesic
      effects of hydroalcoholic Rhus coriaria leaf extract (HRCLE) in a rat model.
      MATERIALS AND METHODS: A total of 42 adult male rats were divided into seven
      groups: a control group (the animals did not receive any drug), three HRCLE
      groups, (receiving 80, 100, and 300 mg/kg, intraperitoneally [ip]), a morphine
      group (1 mg/kg, ip) an aspirin group (1 mg/kg, ip), and a group that received 300
      mg/kg of HRCLE plus naloxone (1 mg/kg, ip). The analgesic effects of HRCLE were
      assessed via writhing, tail flick, and formalin tests, and the data obtained were
      compared with the control group using one-way analysis of variance and Tukey post
      hoc tests. RESULTS: HRCLE significantly inhibited the number of contractions
      induced by acetic acid in the writhing test at all doses, while anti-nociceptive
      activity was only shown at the 100 mg/kg dose (in the chronic phase) and at the
      300 mg/kg dose (in the chronic-acute phase) in the formalin test. Interestingly,
      the greatest effect was observed at the 300 mg/kg HRCLE dose in the tail flick
      test. Simultaneous utilization of naloxone and HRCLE inhibited the anti
      nociceptive effect of the extract in all tests. It is worth mentioning that
      aspirin and morphine revealed anti-nociceptive effects in all tests. CONCLUSIONS:
      Our findings suggest that the analgesic effect of HRCLE may be mediated via both
      peripheral and central mechanisms. The presence of flavonoids might be
      responsible for the anti-nociceptive activity of this plant.

PMID- 27047793
TI  - Cognitive and Psychomotor Function Changes Among Anesthesiology Residents After
      12 Working Hours in Elective Anesthesia Service.
AB  - BACKGROUND: The practice of anesthesia requires good awareness, parallel decision
      making and fine motor skills. The duration of working hours of anesthesiology
      residents is often more than 12 hours. OBJECTIVES: This study aimed to measure
      cognitive and psychomotor functions of anesthesiology residents after 12 working
      hours. PATIENTS AND METHODS: This was an observational study on anesthesiology
      residents who underwent 12 working hours. Each subject, who fulfilled inclusion
      and exclusion criteria, had their cognitive and psychomotor functions tested at 0
      and 12 hours. The cognitive function was measured by "Cognitive Stimulation"
      test, while the psychomotor function was measured by the grooved pegboard.
      Statistical analysis was conducted to compare the results between 0 and 12 hours.
      RESULTS: Cognitive Stimulation" test revealed statistically significant decrease
      at sequential image frequency stimulation (P = 0.035). Other stimulation tests
      did not show any statistically significant result. Grooved pegboard test showed
      statistically significant decrease in psychomotor function from 0 to 12 hours (P
      = 0.037). CONCLUSIONS: There was a decrease in cognitive function, including
      attention, visual memory, naming, and executive function, as well as psychomotor
      function among residents of Department of Anesthesiology and Intensive Care,
      Faculty of Medicine, Universitas Indonesia, who underwent 12 working hours.

PMID- 27047794
TI  - Lidocaine as an Induction Agent for Intracranial Aneurysm Surgery: A Case Series.
AB  - INTRODUCTION: Induction of anaesthesia and its associated spikes in blood
      pressure can cause rupture of an aneurysm during intracranial surgery. Lidocaine
      can reportedly provide hemodynamic stability when applied before endotracheal
      intubation. Rapid injection of large doses of lidocaine can cause
      unconsciousness. CASE PRESENTATION: Lidocaine was applied as the sole anaesthetic
      for induction and maintenance during aneurysm surgery in four patients undergoing
      intracranial aneurysm surgery. Blood pressure alteration after induction and
      during surgery, bleeding, brain laxity, intracranial pressure and extubation time
      were acceptable. CONCLUSIONS: Although propofol remains a standard agent for such
      types of surgeries, lidocaine proved equally effective and coupled with its low
      cost, minimal side effects and omission of other hypnotic agents was a plausible
      induction agent and a maintenance drug in the selected cases.

PMID- 27047796
TI  - Monte Carlo Calculations Supporting Patient Plan Verification in Proton Therapy.
AB  - Patient's treatment plan verification covers substantial amount of the quality
      assurance (QA) resources; this is especially true for Intensity-Modulated Proton
      Therapy (IMPT). The use of Monte Carlo (MC) simulations in supporting QA has been
      widely discussed, and several methods have been proposed. In this paper, we
      studied an alternative approach from the one being currently applied clinically
      at Centro Nazionale di Adroterapia Oncologica (CNAO). We reanalyzed the
      previously published data (Molinelli et al. (1)), where 9 patient plans were
      investigated in which the warning QA threshold of 3% mean dose deviation was
      crossed. The possibility that these differences between measurement and
      calculated dose were related to dose modeling (Treatment Planning Systems (TPS)
      vs. MC), limitations on dose delivery system, or detectors mispositioning was
      originally explored, but other factors, such as the geometric description of the
      detectors, were not ruled out. For the purpose of this work, we compared
      ionization chambers' measurements with different MC simulation results. It was
      also studied that some physical effects were introduced by this new approach, for
      example, inter-detector interference and the delta ray thresholds. The
      simulations accounting for a detailed geometry typically are superior
      (statistical difference - p-value around 0.01) to most of the MC simulations used
      at CNAO (only inferior to the shift approach used). No real improvement was
      observed in reducing the current delta ray threshold used (100 keV), and no
      significant interference between ion chambers in the phantom were detected (p
      value 0.81). In conclusion, it was observed that the detailed geometrical
      description improves the agreement between measurement and MC calculations in
      some cases. But in other cases, position uncertainty represents the dominant
      uncertainty. The inter-chamber disturbance was not detected for the therapeutic
      protons energies, and the results from the current delta threshold are acceptable
      for MC simulations in IMPT. 

PMID- 27047795
TI  - Transcription Factors in the Cellular Response to Charged Particle Exposure.
AB  - Charged particles, such as carbon ions, bear the promise of a more effective
      cancer therapy. In human spaceflight, exposure to charged particles represents an
      important risk factor for chronic and late effects such as cancer. Biological
      effects elicited by charged particle exposure depend on their characteristics,
      e.g., on linear energy transfer (LET). For diverse outcomes (cell death,
      mutation, transformation, and cell-cycle arrest), an LET dependency of the effect
      size was observed. These outcomes result from activation of a complex network of
      signaling pathways in the DNA damage response, which result in cell-protective
      (DNA repair and cell-cycle arrest) or cell-destructive (cell death) reactions.
      Triggering of these pathways converges among others in the activation of
      transcription factors, such as p53, nuclear factor kappaB (NF-kappaB), activated
      protein 1 (AP-1), nuclear erythroid-derived 2-related factor 2 (Nrf2), and cAMP
      responsive element binding protein (CREB). Depending on dose, radiation quality,
      and tissue, p53 induces apoptosis or cell-cycle arrest. In low LET radiation
      therapy, p53 mutations are often associated with therapy resistance, while the
      outcome of carbon ion therapy seems to be independent of the tumor's p53 status.
      NF-kappaB is a central transcription factor in the immune system and exhibits pro
      survival effects. Both p53 and NF-kappaB are activated after ionizing radiation
      exposure in an ataxia telangiectasia mutated (ATM)-dependent manner. The NF
      kappaB activation was shown to strongly depend on charged particles' LET, with a
      maximal activation in the LET range of 90-300 keV/MUm. AP-1 controls
      proliferation, senescence, differentiation, and apoptosis. Nrf2 can induce
      cellular antioxidant defense systems, CREB might also be involved in survival
      responses. The extent of activation of these transcription factors by charged
      particles and their interaction in the cellular radiation response greatly
      influences the destiny of the irradiated and also neighboring cells in the
      bystander effect. 

PMID- 27047798
TI  - Editorial: Combination Strategies in the Treatment of Melanoma.

PMID- 27047797
TI  - The Application and Outcome of Standard of Care Treatment in Elderly Women with
      Ovarian Cancer: A Literature Review over the Last 10 Years.
AB  - The rising number and increasing longevity of the elderly population calls for
      improvements and potentially a more personalized approach to the treatment of
      cancer in this group. Elderly patients frequently present with a number of
      comorbidities, complicating surgery and chemotherapy tolerability. In the case of
      ovarian cancer, elderly women present with more advanced disease, making the
      issue of providing adequate treatment without significant morbidity critical.
      Most studies support the application of standard of care treatment to elderly
      women with ovarian cancer, yet it seems to be offered less frequently in the
      elderly. The objective of this review is to examine the application and outcome
      of standard of care treatment in elderly women with ovarian cancer. The aim is to
      ultimately improve the approach to treatment in this group. 

PMID- 27047799
TI  - Heritable Cancer Syndromes Related to the Hypoxia Pathway.
AB  - Families of tumor-suppressor genes, such as those involved in homologous
      recombination or mismatch repair, contain individual genes implicated in
      hereditary cancer syndromes. Collectively, such groupings establish that
      inactivating germline changes in genes within pathways related to genomic repair
      can promote carcinogenesis. The hypoxia pathway, whose activation is associated
      with aggressive and resistant sporadic tumors, is another pathway in which tumor
      suppressor genes have been identified. von Hippel-Lindau disease, some of the
      hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes, and the syndrome
      of hereditary leiomyomatosis and renal cell carcinoma are heritable conditions
      associated with genes involved or associated with the hypoxia pathway. This
      review links these heritable cancer syndromes to the hypoxia pathway while also
      comparing the relative aggression and treatment resistance of syndrome-associated
      tumors to similar, sporadic tumors. The reader will become aware of shared
      phenotypes (e.g., PGL/PCC, renal cell carcinoma) among these three hypoxia
      pathway-associated heritable cancer syndromes as well as the known associations
      of tumor aggressiveness and treatment resistance within these pathways. 

PMID- 27047800
TI  - Gaps between Evidence and Practice in Postoperative Radiotherapy for Prostate
      Cancer: Focus on Toxicities and the Effects on Health-Related Quality of Life.
AB  - Adjuvant radiotherapy (ART) after prostatectomy for patients with high-risk
      features [extracapsular extension (ECE), seminal vesicle invasion (SVI), and
      positive margin] has been shown to be associated with improved biochemical
      disease-free survival in three large randomized trials and with improved overall
      survival in one. Similarly, salvage radiotherapy (SRT) can effectively achieve
      biochemical control in a significant proportion of patients with a rising PSA
      after surgery. Nonetheless, both approaches of postoperative RT remain highly
      underutilized. This might be partly due to concerns with overtreatment inherent
      to adjuvant approaches, and/or hesitance about causing radiation toxicities and
      their subsequent effects on the patient's quality of life. Herein, we review the
      literature lending evidence to these arguments. We show recent series of ART/SRT
      and their low rates of acute and long-term toxicities, translating only in
      transient decline in quality-of-life (QoL) outcomes. We conclude that concerns
      with side effects should not preclude the recommendation of an effective and
      curative-intent therapy for men with prostate cancer initially treated with
      radical surgery. 

PMID- 27047802
TI  - Genotoxicity of Cytolethal Distending Toxin (CDT) on Isogenic Human Colorectal
      Cell Lines: Potential Promoting Effects for Colorectal Carcinogenesis.
AB  - The composition of the human microbiota influences tumorigenesis, notably in
      colorectal cancer (CRC). Pathogenic Escherichia coli possesses a variety of
      virulent factors, among them the Cytolethal Distending Toxin (CDT). CDT displays
      dual DNase and phosphatase activities and induces DNA double strand breaks, cell
      cycle arrest and apoptosis in a broad range of mammalian cells. As CDT could
      promote malignant transformation, we investigated the cellular outcomes induced
      by acute and chronic exposures to E. coli CDT in normal human colon epithelial
      cells (HCECs). Moreover, we conducted a comparative study between isogenic
      derivatives cell lines of the normal HCECs in order to mimic the mutation of
      three major genes found in CRC genetic models: APC, KRAS, and TP53. Our results
      demonstrate that APC and p53 deficient cells showed impaired DNA damage response
      after CDT exposure, whereas HCECs expressing oncogenic KRAS (V12) were more
      resistant to CDT. Compared to normal HCECs, the precancerous derivatives exhibit
      hallmarks of malignant transformation after a chronic exposure to CDT. HCECs
      defective in APC and p53 showed enhanced anchorage independent growth and genetic
      instability, assessed by the micronucleus formation assay. In contrast, the
      ability to grow independently of anchorage was not impacted by CDT chronic
      exposure in KRAS(V12) HCECs, but micronucleus formation is dramatically
      increased. Thus, CDT does not initiate CRC by itself, but may have promoting
      effects in premalignant HCECs, involving different mechanisms in function of the
      genetic alterations associated to CRC. 

PMID- 27047801
TI  - Pseudomonas aeruginosa N-3-oxo-dodecanoyl-homoserine Lactone Elicits Changes in
      Cell Volume, Morphology, and AQP9 Characteristics in Macrophages.
AB  - Quorum sensing (QS) communication allows Pseudomonas aeruginosa to collectively
      control its population density and the production of biofilms and virulence
      factors. QS signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O
      C12-HSL), can also affect the behavior of host cells, e.g., by modulating the
      chemotaxis, migration, and phagocytosis of human leukocytes. Moreover, host water
      homeostasis and water channels aquaporins (AQP) are critical for cell morphology
      and functions as AQP interact indirectly with the cell cytoskeleton and signaling
      cascades. Here, we investigated how P. aeruginosa 3O-C12-HSL affects cell
      morphology, area, volume and AQP9 expression and distribution in human primary
      macrophages, using quantitative PCR, immunoblotting, two- and three-dimensional
      live imaging, confocal and nanoscale imaging. Thus, 3O-C12-HSL enhanced cell
      volume and area and induced cell shape and protrusion fluctuations in
      macrophages, processes tentatively driven by fluxes of water across cell membrane
      through AQP9, the predominant AQP in macrophages. Moreover, 3O-C12-HSL
      upregulated the expression of AQP9 at both the protein and mRNA levels. This was
      accompanied with enhanced whole cell AQP9 fluorescent intensity and
      redistribution of AQP9 to the leading and trailing regions, in parallel with
      increased cell area in the macrophages. Finally, nanoscopy imaging provided
      details on AQP9 dynamics and architecture within the lamellipodial area of 3O-C12
      HSL-stimulated cells. We suggest that these novel events in the interaction
      between P. aeruginosa and macrophage may have an impact on the effectiveness of
      innate immune cells to fight bacteria, and thereby resolve the early stages of
      infections and inflammations. 

PMID- 27047803
TI  - Place of mTOR inhibitors in management of BKV infection after kidney
      transplantation.
AB  - CONTEXT: BK virus (BKV) viremia and BKV-associated nephropathy (BKVAN) have
      become a serious nuisance to kidney transplant (KT) patients since the mid
      nineties, when the incidence of this disease has increased significantly.
      EVIDENCE ACQUISITION: Directory of open access journals (DOAJ), EMBASE, Google
      Scholar, PubMed, EBSCO, and Web of Science have been searched. RESULTS: Many
      hypothesis have been made as to why this phenomenon has developed; it is of
      general opinion that a more potent immunosuppression is at the core of the
      problem. The use of the association of tacrolimus (TAC) with mycophenolic acid
      (MPA) has gained momentum in the same years as the increase in BKV viremia
      incidence making it seem to be the most likely culprit. m-TOR inhibitors (m
      TORIs) have been shown to have antiviral properties in vitro and this fact has
      encouraged different transplant teams to use these agents when confronted with
      BKV infection (viremia or nephropathy). However, the results are mitigated. There
      had been conflicting results for example when converting from TAC-to sirolimus
      based immunosuppression in the setting of established BKVAN. CONCLUSIONS: In
      order to prevent BKV infection we have to minimize to some extent
      immunosuppression, but it is not always possible, e.g. in high immunological risk
      patients. Conversely, we could use m-TORIs associated with low-dose calcineurin
      inhibitors (CNIs). This could be actually the key to a safe immunosuppression
      regimen both from the immunological stand point and from the viral one.

PMID- 27047804
TI  - An update on renal involvement in hemophagocytic syndrome (macrophage activation
      syndrome).
AB  - CONTEXT: Hemophagocytic syndrome (HPS) is mainly characterized by massive
      infiltration of bone marrow by activated macrophages and often presents with
      pancytopenia. Thrombotic microangiopathy (TMA) is also present with
      thrombocytopenia and renal involvement. Both conditions could coexist with each
      other and complicate the condition. EVIDENCE ACQUISITION: Directory of Open
      Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science
      with keywords relevant to; Hemophagocytic syndrome, macrophage activation
      syndrome, interferon-gamma and thrombotic microangiopathy, have been searched.
      RESULTS: Viral infection, rheumatologic disease and malignancies are the main
      underlying causes for secondary HPS. calcineurin inhibitors and viral infections
      are also the main underlying causes of TMA in transplant recipients. In this
      review, we discussed a 39-year-old male who presented with pancytopenia and renal
      allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition
      and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and
      plasmapheresis therapy. CONCLUSIONS: HPS is an increasingly recognized disorder
      in the realm of different medical specialties. Renal involvement complicates the
      clinical picture of the disease, and this condition even is more complex in renal
      transplant recipients. We should consider the possibility of HPS in any renal
      transplant recipient with pancytopenia and allograft dysfunction. The combination
      of HPS with TMA future increases the complexity of the situation.

PMID- 27047805
TI  - On the occasion of world kidney day 2016; work together to better protect the
      kidney.
AB  - CONTEXT: World kidney day is a yearly global alertness and education ceremony,
      held on the second Thursday in March. EVIDENCE ACQUISITION: Directory of open
      access journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science
      have been searched. RESULTS: Once again we reached to March 14, the world kidney
      day of 2016. This is the 10th anniversary of world kidney day, a program of the
      International Society of Nephrology (ISN) and the International Federation of
      Kidney Foundations (IFKF). World kidney day first began in 2006 and the worldwide
      campaign highlights a specific theme each year. The theme for 2015 was to invite
      everybody to drink a glass of water and give one, too, to celebrate their
      kidneys. This is a symbolic action to memorize that kidneys are vital organs and
      that they might be cared. CONCLUSIONS: It is a manner to make individuals more
      conscious about their lifestyle choices. In this year, world kidney day will be
      celebrated on Thursday March 10, 2016. The theme for 2016 will highlight on renal
      disease and children.

PMID- 27047806
TI  - Early post-transplant complications following ABO-incompatible kidney
      transplantation.
AB  - BACKGROUND: Living-kidney transplantation is increasing because of the scarcity
      of kidneys from deceased donors and the increasing numbers of patients on waiting
      lists for a kidney transplant. Living-kidney transplantation is now associated
      with increased long-term patient- and allograft-survival rates. OBJECTIVES: The
      purpose of this retrospective study was to identify, in a cohort of 44 ABO
      incompatible (ABOi) live-kidney transplant patients, the main complications that
      occurred within 6 months post-transplantation, and to compare these findings with
      those from 44 matched ABO-compatible (ABOc) live-kidney transplant patients who
      were also from our center. PATIENTS AND METHODS: This single-center retrospective
      study assessed post-transplantation complications in 44 ABO-i versus 44 matched
      ABO-c patients. All patients were comparable at baseline except that ABO-i
      patients had greater immunological risks. RESULTS: During the 6-month post
      transplant period, more ABO-i patients presented with postoperative bleeds, thus
      requiring significantly more blood transfusions. Bleeds were associated with
      significantly lower values of fibrinogen, platelets, prothrombin time, and
      hemoglobin levels. Surgical complications, patient- and graft-survival rates, and
      kidney-function statuses were similar between both groups at 6 months post
      transplantation. CONCLUSIONS: We conclude that impairment of hemostatic factors
      at pre-transplant explained the increased risk of a post-transplant bleed in ABO
      i patients.

PMID- 27047807
TI  - Correlation of plasma interleukin-18 concentration and severity of renal
      involvement and disease activity in systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      characterized by activation of T and polyclonal B lymphocytes. IL-18 was
      originally identified as a factor which enhances IFN-gamma production and is a
      potent inducer of the inflammatory mediators by T cells, causing severe
      inflammatory disorders in SLE. OBJECTIVES: This study aimed to evaluate the
      association of plasma interlukine-18 (IL-18) concentration and severity of lupus
      nephritis (LN) and disease activity in SLE patients. PATIENTS AND METHODS: In
      this cross-sectional study, 113 patients with SLE and 50 healthy individuals were
      examined. Serum level of IL-18 was measured. The severity and activity of the
      disease was determined by Systemic Lupus Erythematosus Disease Activity Index
      (SLEDAI) score. The severity of kidney involvement was studied by renal biopsy,
      serum creatinine and 24 hours urine protein level. RESULTS: The mean level of
      serum IL-18 was significantly higher in the patients than controls (577.67 +/-
      649.95 versus 60.48 +/- 19.53 pg/ml; P < 0.001). In SLE patients with active
      disease level of serum IL-18 was significantly higher than chronic disease
      (622.77 +/- 716.54 versus 182 +/- 184.37 pg/ml; P < 0.001). The serum level of IL
      18 was significantly higher in stage IV (P < 0.001) and V (P < 0.001) of patients
      with LN, than other stages. CONCLUSIONS: The current study showed that the serum
      IL-18 is significantly higher in the patients than controls and it significantly
      correlated with sever renal involvement and disease activity in SLE patients.

PMID- 27047808
TI  - Evaluation of leflunomide for the treatment of BK viremia and biopsy proven BK
      nephropathy; a single center experience.
AB  - BACKGROUND: BK virus reactivation is a significant complication following renal
      transplantation that can result in graft failure. Reduction of immunosuppression
      and substitution of leflunomide for mycophenolate mofetil (MMF) has been used to
      treat this entity. OBJECTIVES: To evaluate the use of leflunomide in BK viremia
      (BKV) and biopsy proven BK nephropathy (BKN) in kidney and kidney-pancreas
      transplant recipients. PATIENTS AND METHODS: We retrospectively reviewed 28
      kidney and kidney-pancreas transplant recipients who had received leflunomide for
      BKV from January 2006 to November 2012. Demographics, time to BKV diagnosis,
      biopsy findings, rejection episodes, and laboratory data were recorded. RESULTS:
      The average (mean +/- SD) time to BKV from time of transplant was 316.1 +/- 368.0
      days (62-1708 days). At time of diagnosis, 64% of patients had their maintenance
      immunosuppression reduced. The indications for leflunomide administration were;
      BKV and biopsy proven acute rejection (BPAR) (50%), biopsy proven BKN (18%), or
      persistent BKV (25%). Therapeutic levels (50-100 mcg/mL) were achieved in only
      54% of patients, and 60% of them had required a leflunomide dose of at least 60
      mg/day. BK virus was cleared from the serum on average of 151 +/- 145.2 days (17
      476 days). At study commencement, 29% of patients had remained on leflunomide due
      to persistent BKV. CONCLUSIONS: In our study, most patients required at least a
      60 mg daily dose of leflunomide to achieve therapeutic levels and to clear the
      virus compared to the standard 40 mg daily dose. Delaying therapy may result in
      progressive BKV and BKN.

PMID- 27047809
TI  - Effects of coenzyme Q10 supplementation on C-reactive protein and homocysteine as
      the inflammatory markers in hemodialysis patients; a randomized clinical trial.
AB  - BACKGROUND: The most leading cause of death in end-stage renal disease (ESRD)
      patients are cardiovascular disease and inflammatory markers are related to
      coronary events. CO-Q10 (coenzyme Q10) is a protective supplement from free
      radical oxidative damage. In addition, hyperhomocysteinemia is an independent
      coronary artery disease (CAD) risk factor. OBJECTIVES: Due to increasing
      oxidative stress in dialysis patients, and the effect of CO-Q10 in decrease
      oxidative stress, in this work, we assessed the effect of CO-Q10 on C-reactive
      protein (CRP) level as an inflammatory marker and homocysteine in dialysis
      patients. PATIENTS AND METHODS: This was a single-blind, randomized cross over
      clinical trial. Patients with ESRD were randomly allotted to two groups. All
      patients received placebo and C0- Q10 100mg/d during the three months in each
      stage, with two week washout period. Plasma level of CRP and homocysteine from
      the start of the work and at the conclusion of each menses, are evaluated.
      RESULTS: Thirty-four patients randomized, but 26 patients complete study
      protocol. The treatment effect of CO-Q10 on CRP level is significant (P < 0.001)
      (95% CI = -20.1 to -10.5) and it was also significant for the increasing albumin
      level. (P = 0.044) (95% CI = 0. 0-0.6), But there was not any substantial effect
      on serum homocysteine level (P = 0.630). CONCLUSIONS: CO-Q10 could significantly
      decrease CRP level as an inflammatory marker and can protect cardiovascular
      events.

PMID- 27047810
TI  - An ethno-medicinal study of medicinal plants used for the treatment of diabetes.
AB  - BACKGROUND: Diabetes is the greatest public health problem and is considered as
      the silent epidemic of the 21st century. In Iran, there are approximately 1.5
      million diabetic patients. Before the discovery of insulin, medicinal plants were
      widely used for the treatment of diabetes in Iran. OBJECTIVES: This study aimed
      to determine the indigenous plants used for the treatment of diabetes in Shiraz,
      southwest of Iran. MATERIALS AND METHODS: Semi-structured direct interviews were
      conducted with 25 herbalists to identify medicinal plants used to treat diabetes.
      Questionnaires were included herbalist personal information, plant local name,
      growth season, plant parts used, preparation methods, and traditional therapies.
      RESULTS: The interview data indicated that, 24 medicinal plants from 19 families
      are used for the treatment of diabetes in Shiraz. The families with most
      antidiabetic species were Compositae (13%), Rosaceae (13%) and Cucurbitaceae
      (8%). The most frequently used plant parts were fruits (38%) and the most common
      preparation method was decoction (62%). For 45% of reported plants,
      pharmaceutical studies approved antidiabetic effects in animal or humane model of
      diabetes. RESULTS of this study showed that the plants recommended by Shirazian
      herbalists have potential antidiabetic effects. CONCLUSIONS: It is suggested that
      the ingredients of indigenous plants be studied to determine therapeutic effects
      and mechanism of action. If they were safe and effective, they can be refined and
      processed to produce natural drugs.

PMID- 27047811
TI  - Distal, intermediate, and proximal mediators of racial disparities in renal
      disease mortality in the United States.
AB  - BACKGROUND: Kidney failure and associated mortality is one of the major
      components of racial disparities in the United States. OBJECTIVES: The current
      study aimed to investigate the role of distal (socioeconomic status, SES),
      intermediate (chronic medical diseases), and proximal (health behaviors) factors
      that may explain Black-White disparities in mortality due to renal diseases.
      PATIENTS AND METHODS: This is a nationally representative prospective cohort with
      25 years of follow up. Data came from the Americans' Changing Lives (ACL) study,
      1986 to 2011. The study included 3361 Black (n = 1156) or White (n = 2205) adults
      who were followed for up to 25 years. Race was the main predictor and death due
      to renal disease was the outcome. SES, chronic medical disease (diabetes,
      hypertension, obesity), and health behaviors (smoking, drinking, and exercise) at
      baseline were potential mediators. We used Cox proportional hazards models for
      data analysis. RESULTS: In age and gender adjusted models, Blacks had higher risk
      of death due to renal disease over the follow up period. Separate models
      suggested that SES, health behaviors and chronic medical disease fully explained
      the effect of race on renal disease mortality. CONCLUSIONS: Black-White
      disparities in rate of death due to renal diseases in the United States are not
      genuine but secondary to racial differences in income, health behaviors,
      hypertension, and diabetes. As distal, intermediate, and proximal factors
      contribute to racial disparities in renal disease mortality, elimination of such
      disparities requires a wide range of policies and programs that target income,
      medical conditions, and health behaviors.

PMID- 27047812
TI  - Reply to Hamidian Jahromi and Bastani: Acute early transplant renal artery
      thrombosis; a complex etiologic diagnosis.

PMID- 27047813
TI  - BIOMATERIAL IMPLANTS IN BONE FRACTURES PRODUCED IN RATS FIBULAS.
AB  - To evaluate the importance of collagen and hydroxyapatite in the regeneration of
      fractures experimentally induced in the fibulas of rats. METHOD: 15 rats were
      used. These were subjected to surgery to remove a fragment from the fibula. This
      site then received a graft consisting of a silicone tubes filled with
      hydroxyapatite and collagen. RESULTS: Little bone neoformation occurred inside
      the tubes filled with the biomaterials. There was more neoformation in the tubes
      with collagen. CONCLUSION: The biomaterials used demonstrated biocompatibility
      and osteoconductive capacity that was capable of stimulating osteogenesis, even
      in bones with secondary mechanical and morphological functions such as the fibula
      of rats.

PMID- 27047814
TI  - SYNOVIAL CHONDROMATOSIS.
AB  - A 34-year-old male patient presented severe pain in his left knee in association
      with functional incapacitation, with no apparent triggering factor. He sought
      medical attention in December 2006, at which time he was prescribed NSAIDs. After
      a year, he reported increased swelling and pain at the site. He was referred to a
      knee specialist with a suspected meniscal injury. Upon examination, severe
      swelling of the joint, with movement limitation, severe pain and negative joint
      aspiration, was found. Since the simple radiographic results were normal, an MRI
      of the knee was requested. The MRI revealed a large accumulation of fluid inside
      the joint, together with marked synovial proliferation, especially focal
      thickening in clumps with an intermediate signal in T1 and T2, and a discrete
      hyposignal in T2 that was suggestive of pigmented villonodular synovitis with
      intact meniscus and ligaments. The patient underwent arthroscopy on the left
      knee, which revealed whitish irregular fragments, and then underwent arthrotomy
      with removal of the lesion and extensive synovectomy. The material was sent for
      anatomopathological examination, which showed the presence of synovial
      chondromatosis. Eight months after the surgery, the patient does not have any
      complaints, with a range of motion of 130 degrees  in the left knee without joint
      effusion or signs of inflammation. Synovial chondromatosis is a rare benign type
      of metaplasia of the synovial membrane that leads to the formation of
      cartilaginous free bodies in the joint space. It is difficult to diagnose because
      95% of the nodules, when not calcified, can be overlooked radiologically. 

PMID- 27047815
TI  - CUBOID-NAVICULAR TARSAL COALITION.
AB  - The authors present the case of a nine-year-old female patient who presented with
      pain in her right foot associated with physical activities. After this case was
      diagnosed as cuboid-navicular tarsal coalition, the patient was treated
      surgically with resection of the coalition, thereby resolving the symptoms. The
      literature was reviewed and the importance of adequate physical examination and
      imaging assessment for investigating foot pain in children and adolescents was
      discussed. 

PMID- 27047816
TI  - MUSCLE INJURY - PHYSIOPATHOLOGY, DIAGNOSIS, TREATMENT AND CLINICAL PRESENTATION.
AB  - Skeletal muscle tissue has the largest mass in the human body, accounting for 45%
      of the total weight. Muscle injuries can be caused by bruising, stretching or
      laceration. The current classification divides such injuries into mild, moderate
      and severe. The signs and symptoms of grade I lesions are edema and discomfort;
      grade II, loss of function, gaps and possible ecchymosis; and grade III, complete
      rupture, severe pain and extensive hematoma. The diagnosis can be confirmed by:
      ultrasound, which is dynamic and cheap, but examiner dependent; and tomography or
      magnetic resonance, which gives better anatomical definition, but is static.
      Initial phase of the treatment can be summarized as the "PRICE" protocol. NSAIDs,
      ultrasound therapy, strengthening and stretching after the initial phase and
      range of motion without pain are used in clinical treatment. On the other hand,
      surgery has precise indications: hematoma drainage and muscle-tendon reinsertion
      and reinforcement. 

PMID- 27047817
TI  - WHAT IS THE BEST QUESTIONNAIRE FOR MONITORING THE PHYSICAL CHARACTERISTICS OF
      PATIENTS WITH KNEE OSTEOARTHRITIS IN THE BRAZILIAN POPULATION?
AB  - OBJECTIVE: To measure the validity and reliability of the WOMAC, IKDC and Lysholm
      questionnaires among patients with knee osteoarthritis and determine the
      influence of age on their scores. METHOD: Fifty-seven patients diagnosed with
      primary osteoarthritis of the knee answered the SF-36, WOMAC, IKDC and Lysholm
      questionnaires. Validity was tested by measuring the correlation (Pearson's
      correlation coefficient, "r") between the questionnaires. Internal consistency
      was measured using Cronbach's alpha and concordance was measured through the
      Altman-Bland graphical representations and survival concordance. To determine the
      influence of age on the results, we correlated this variable with the scores from
      the three knee questionnaires using Pearson's coefficient of determination
      ("r2"). RESULTS: IKDC (0.62) and WOMAC (0642) showed moderate to strong
      correlations in relation to the summarized physical capacity score of the SF-36,
      while Lysholm showed moderate correlations (0.555). The Cronbach alpha values for
      IKDC, WOMAC and Lysholm were 0.811, 0.959 and 0.734, respectively. Despite the
      strong correlations between IKDC and WOMAC (0.843), Lysholm and WOMAC (0.759) and
      IKDC and Lysholm (0.858), the Bland-Altman graphical representations and survival
      concordance showed that the concordance between the three questionnaires was low.
      IKDC, Lysholm and WOMAC showed coefficients of determination (r2) with age of
      0.004, 0.010 and 0.043, respectively. CONCLUSION: Age was not found to be a
      limiting factor for the use of any of the questionnaires applied in this study.
      The concordance tests and correlations with the physical components of SF-36
      suggest that WOMAC is more appropriate for assessing physical capacities and
      limitations relating to physical traits, while IKDC seems more appropriate for
      assessing the functional limitations relating to pain.

PMID- 27047818
TI  - ASSESSMENT OF THE REPRODUCIBILITY OF THE OUTERBRIDGE AND FSA CLASSIFICATIONS FOR
      CHONDRAL LESIONS OF THE KNEE.
AB  - OBJECTIVE: To assess the reproducibility of the Outerbridge and the French
      Society of Arthroscopy classifications between different observers, and to
      establish a comparison between them. METHOD: Thirty videos on randomly selected
      knee arthroscopy procedures demonstrating chondral lesions were used. These were
      classified by six observers: two third-year orthopedics residents and four
      orthopedic surgeons, of whom two were knee surgery specialists. The intraobserver
      and interobserver reliability was evaluated by means of the kappa index. RESULTS:
      The result from the complete evaluation on the Outerbridge classification with
      all the observers gave a kappa index of 0.434411. For the classification proposed
      by the French Society of Arthroscopy, the kappa index was 0.45166. CONCLUSION:
      The Outerbridge and French Society of Arthroscopy classifications for chondral
      lesions are moderately reproducible between observers. Comparing the two
      classifications, the proposal from the French Society of Arthroscopy was shown to
      be more reproducible, and the authors suggest that this classification should be
      used preferentially in clinical practice for evaluations on chondral lesions of
      the knee.

PMID- 27047819
TI  - EVALUATION OF THE RESULTS FROM ARTHROSCOPIC REPAIR ON ROTATOR CUFF INJURIES AMONG
      PATIENTS UNDER 50 YEARS OF AGE.
AB  - OBJECTIVE: To assess the results from arthroscopic surgical treatment of rotator
      cuff injuries among patients under 50 years of age. METHODS: Sixty-three patients
      with rotator cuff injuries who underwent arthroscopic surgical treatment
      performed by the Shoulder and Elbow Group of the Department of Orthopedics and
      Traumatology, in the Fernandinho Simonsen wing of Santa Casa Medical School, Sao
      Paulo, between August 1998 and December 2007, were reassessed. The study included
      all patients with rotator cuff injuries who were under 50 years of age and had
      been followed up postoperatively for at least 24 months. RESULTS: According to
      the UCLA evaluation criteria, 59 patients (92%) showed excellent and good
      results; five (8%) showed fair results; and none showed poor results. The
      postoperative evaluation showed that the mean range of motion was 145 degrees 
      for elevation, 47 degrees  for lateral rotation and T10 for medial rotation.
      Unsatisfactory results were associated with prolonged duration of the injury,
      with a statistically significant relationship. CONCLUSION: Arthroscopic repair of
      rotator cuff injuries in young patients produces excellent or good results for
      most patients.

PMID- 27047820
TI  - SURFACE ARTHROPLASTY FOR TREATING PRIMARY AND/OR SECONDARY SHOULDER
      OSTEOARTHROSIS BY MEANS OF THE HEMICAP-ARTHROSURFACE((r)) SYSTEM.
AB  - OBJECTIVE: To present the surgical technique for the He-miCAP-Arthrosurface((r))
      system and evaluate our results from this technique for treating primary and/or
      secondary shoulder osteoarthrosis. METHOD: Between June 2007 and June 2009, 10
      shoulders of 10 patients (nine with primary osteoarthrosis and one with avascular
      necrosis of the humeral head) underwent surface arthroplasty using the HemiCAP
      Arthrosurface((r)) system to correct the problem. The follow-up time ranged from
      six to 29 months (mean of 17 months). The patients' ages ranged from 62 to 73
      years (mean of 67.5 years). Six patients were female and four patients were male.
      The patients were followed up weekly for the first month after the surgical
      procedure and every three months thereafter. The clinic evaluation was done using
      the criteria of the University of California at Los Angeles (UCLA) and a visual
      analogue pain scale. RESULTS: All the patients said that they were satisfied with
      the results from the surgical treatment, with a mean UCLA score of 30 points and
      a mean analogue pain score of two points. CONCLUSION: The HemiCAP
      Arthrosurface((r)) system for shoulder surgery for a specific group of patients
      is a technique that preserves the bone stock with good functional and antalgic
      results.

PMID- 27047822
TI  - EVALUATION OF SURGICAL TREATMENT OF FRACTURES OF THORACOLUMBAR SPINE WITH THIRD
      GENERATION MATERIAL FOR INTERNAL FIXATION.
AB  - OBJECTIVE: To evaluate the functional results from patients with surgical
      fractures in the thoracolumbar spine. METHOD: A prospective study including 100
      patients with spinal fractures in the thoracic and lumbar segments was conducted.
      The lesions were classified in accordance with the AO system, and the patients
      were treated surgically. The presence of early kyphosis and its evolution after
      the surgical intervention, and the presence of postoperative pain and its
      evolution up to the 24(th) week after the surgery, were evaluated. We compared
      our data with the literature. RESULTS: One hundred surgical patients were
      analyzed, of which 37 were type A, 46 were type B and 17 were Type C. Patients
      who presented Frankel A kept their clinical status, but patients with Frankel B
      or higher evolved with some improvement. The average improvement in pain based on
      a visual analog scale was more than four points. All the patients were able to
      return to their daily routine activities, although we did not take the return to
      work to be an assessment criterion. CONCLUSION: Despite controversy regarding the
      indications for surgery in cases of fractured spine, we believe that the method
      that we used was satisfactory because of the good results and low complication
      rate. However, more randomized prospective studies with longer follow-up are
      needed in order to evaluate this type of fixation.

PMID- 27047821
TI  - RADIOGRAPHIC ABNORMALITIES OF THE TALUS IN PATIENTS WITH CLUBFOOT AFTER SURGICAL
      RELEASE USING THE MCKAY TECHNIQUE.
AB  - OBJECTIVE: To analyze morphological abnormalities of the talus in patients with
      clubfoot after surgical treatment using the McKay technique. METHOD: Lateral
      standing-position radiographs of the feet of 14 patients with unilateral clubfoot
      who underwent treatment by means of the doubleincision McKay technique were
      retrospectively analyzed. All the patients were operated by the same surgeon,
      with an average of 6.53 years between surgery and the radiograph. We compared the
      radiographic characteristics of the talus between the operated and the
      contralateral foot. We assessed the presence of deformity of the talar dome and
      head (sphericity evaluation); the talar length and height; the percentage and
      degree of navicular subluxation; abnormalities of the Gissane angle; and the
      trabecular bone pattern. RESULTS: Abnormalities of the talar head occurred in
      92.8% of the patients; of the talar dome in 92.8%; and of the trabecular pattern
      in 100%. The talar length ratio between the operated and the contralateral foot
      ranged from 0.61 to 0.88 (mean 0.79; SD = 0.09), while the height ratio ranged
      from 0.57 to 0.98 (mean 0.82; SD = 0.12). The Gissane angle was greater in all of
      the operated feet, and all of them also showed navicular subluxation, at a rate
      ranging from 6.43 to 59.75% (mean 26.34%; SD = 16.66%). CONCLUSION: Talar
      abnormalities occurred in 100% of the feet treated using the McKay technique. It
      was shown that establishing radiographic parameters to describe and quantify
      these deformities was feasible, through simple and easy-to-perform techniques.

PMID- 27047823
TI  - IMMEDIATE AND LATE EFFECT OF SUTURES IN EXTRASYNOVIAL TENDONS: BIOMECHANICAL
      STUDY IN RATS.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects on the mechanical
      properties of rats' calcaneus tendons, of repair arrangements using suture
      material in the absence of any healing process. METHOD: Twelve male Wistar rats
      were used. They were subjected to placement of a modified Kessler suture stitch
      in the calcaneus tendon. The sacrifices were performed immediately after and six
      weeks after the operation. The mechanical properties studied were maximum load,
      tension in the maximum load and module of elasticity. The contralateral tendon
      was used as a control. RESULTS: The statistical analysis showed that for the
      times studied, the values for mechanical properties did not present any
      significant differences. In relation to the control, i.e. the contralateral
      tendon without a suture, the results demonstrated that, six weeks after the
      operation, the values for the modulus of elasticity were lower, whereas there
      were no significant variations in maximum load or tension at maximum load.
      CONCLUSION: Placement of suture material on an extrasynovial tendon without
      lesions decreased the modulus of elasticity, but it did not interfere with the
      maximum load or tension at maximum load, six weeks after the operation.

PMID- 27047824
TI  - COMPARATIVE ANATOMICAL STUDY BETWEEN THE RIGHT AND LEFT SIDES OF THE AXILLARY
      NERVE IN RELATION TO DELTOPECTORAL APPROACH AND ACROMION.
AB  - OBJECTIVE: To establish anatomical parameters for the axillary nerve by measuring
      the distances to the acromion and the deltopectoral access, and to ascertain
      whether there are any differences in comparative measurements between the left
      and right sides. METHOD: An anatomical study on the path of the axillary nerve
      was conducted by dissecting 30 shoulders of 20 fresh adult cadavers. For
      comparative study, bilateral dissection was performed on 10 cadavers. Digital
      caliper gauges, accurate to the nearest 0.05 cm, were used to measure the
      distances between the lateral extremity of the acromion and the anterior and
      posterior branches of the axillary nerve, and between the deltopectoral space and
      the anterior branch of the axillary nerve. RESULTS: The shortest distance between
      the acromion and the axillary nerve was 5.47 cm, and the greatest distance was
      7.06 cm. The shortest distance between the deltopectoral groove and the axillary
      nerve was 3.94 cm. A statistically significant difference was found using
      Wilcoxon's test in comparative measurements between the left and right sides for
      the distances between the posterior branch of the axillary nerve and the midpoint
      of the lateral border of the acromion (A-E), and between the anterior branch of
      the axillary nerve and the anterior extremity of the acromion (B-C), both of
      which were larger on the right side. CONCLUSIONS: The axillary nerve was situated
      between 5.47 and 7.06 cm distally to the acromion, and 3.94 cm laterally to the
      deltopectoral space. There was a statistically significant difference in the
      comparison between the left and right sides, and both measurements were larger on
      the right side.

PMID- 27047825
TI  - PATHOLOGICAL FRACTURE OF LUMBAR VERTEBRA IN CHILDREN WITH ACUTE NEUROLOGICAL
      DEFICIT: CASE REPORT.
AB  - This study reports on a case of lymphoma in a 13-year-old patient who came to a
      consultation with lumbar pain. The patient had suffered low-intensity trauma in
      the lumbar region that resulted in persistent pain of progressive nature. In an
      emergency evaluation, radiographic examination showed a spinal fracture. The
      patient was then sent to the specialist outpatient clinic of the same hospital.
      The initial examinations confirmed the diagnosis of a pathological fracture
      surrounded by a tissue mass, thus indicating the presence of a tumor.
      Subsequently, the patient evolved with lower-limb paresthesia and urine
      retention, without any pathological diagnosis for the lesion. The patient then
      underwent emergency surgery to achieve stabilization and neurological
      decompression, and material from the lesion was sent for anatomopathological
      examination. The result from the anatomopathological examination suggested that
      the lesion was a small-cell tumor, although leaving some doubt.
      Immunohistochemistry defined the diagnosis of lymphoma. The patient was then sent
      for oncological treatment. The aim of this study was to report on a rare case of
      lymphoma in a child with an initial diagnosis of a pathological fracture in the
      lumbar spine. It is important to investigate fractures associated with mild
      trauma in children. Precise diagnosis results in effective attendance with better
      results for these patients. This patient underwent chemotherapy and achieved a
      good response, with positive repercussions for his prognosis. 

PMID- 27047826
TI  - BILATERAL ANTERIOR GLENOHUMERAL DISLOCATION: CLINICAL CASE.
AB  - Bilateral anterior glenohumeral dislocation is a rare occurrence. We present a
      case of bilateral anterior glenohumeral dislocation caused by a fall. The
      interest in publishing this case is that this is a clinical rarity with few cases
      reported in the literature. An 89-year-old female patient was brought to the
      emergency department after a fall, complaining of intense pain in both shoulders
      and inability to move them. Objective examination showed clinical signs giving
      the suspicion of bilateral anterior glenohumeral dislocation, which was confirmed
      by x-ray imaging. Both dislocations were successfully reduced in the emergency
      department using the modified Milch technique. When a synchronous and symmetrical
      force has acted on both shoulders and these are painful with significant
      functional limitation, the suspicion of bilateral glenohumeral dislocation is a
      differential diagnosis to be considered, even though it is rare. 

PMID- 27047827
TI  - INDICATIONS FOR DISTAL RADIOULNAR ARTHROPLASTY: REPORT ON THREE CLINICAL CASES.
AB  - Distal radioulnar arthroplasty is an attractive solution for treating various
      pathological conditions of the distal radioulnar joint because it allows
      restoration of stability, load transmission and function. The main indications
      are: radioulnar impingement after partial or complete resection of the distal
      ulna; and degenerative, inflammatory or post-traumatic arthritis of the distal
      radioulnar joint. The authors present three clinical cases of distal radioulnar
      pathological conditions: two patients with post-traumatic sequelae and one case
      of distal radioulnar impingement after a Sauve-Kapandji operation. The three
      cases were treated surgically with a metallic prosthesis to replace the distal
      ulna (First Choice - Ascension((r))). The first two were treated with a
      resurfacing prosthesis and the last one with a modular prosthesis. All of the
      patients had achieved pain relief and increased movement of the distal radioulnar
      joint after one year of postoperative follow-up. 

PMID- 27047828
TI  - FRACTURE OF THE TIBIAL COMPONENT IN TOTAL KNEE ARTHROPLASTY: REPORT ON TWO CASES.
AB  - The authors report the rare occurrence of two cases of fracture of the tibial
      component in total knee arthroplasty. They review the literature and discuss the
      main factors that can cause failure of the implants. 

PMID- 27047829
TI  - A SIMPLIFIED WAY OF DETERMINING THE DIRECTION OF A SINGLE-CUT OSTEOTOMY TO
      CORRECT COMBINED ROTATIONAL AND ANGULAR DEFORMITIES OF LONG BONES.
AB  - The direction of the obliquity of the cut for performing single-cut osteotomy to
      correct combined angular and rotational deformities is difficult to determine.
      The appropriate obliquity, i.e. whether clockwise or anticlockwise in relation to
      the perpendicular to the bone axis, is usually determined through trials using
      plastic bone models to imitate the deformity, or on bananas, on which different
      simulations can be made. This is very confusing and difficult. In this study, we
      propose a table, with entries for angular and rotational deformities and the
      affected side. The correct obliquity of the cut in relation to the perpendicular
      to the diaphyseal axis is directly indicated in the table. A step-by-step review
      of the preoperative planning of the single-cut osteotomy is also presented, with
      emphasis on the proposed contribution. 

PMID- 27047830
TI  - Will There be a Future for the RBO?

PMID- 27047831
TI  - SCHEUERMANN'S KYPHOSIS: COMPARISON BETWEEN THE POSTERIOR APPROACH ASSOCIATED WITH
      SMITH-PETERSEN OSTEOTOMY AND COMBINED ANTERIOR-POSTERIOR FUSION.
AB  - OBJECTIVE: Surgical treatment of Scheuermann's kyphosis (SK) remains a subject
      under discussion. In view of the controversy over the best form of surgical tr
      otomy. METHODS: This was a descriptive case-control study with cross-sectional
      analysis. Twenty-eight patients, split into two groups conducted at different
      times, were evaluated. RESULTS: The first group comprised patients treated using
      the double approach, with an average age of 19 years, preoperative kyphosis of
      77.6 degrees , postoperative kyphosis of 35.8 degrees  and average correction of
      53.2%. The second group comprised patients treated using the posterior route
      associated with Smith-Petersen osteotomy, with a mean age of 27.3 years,
      preoperative kyphosis of 72.9 degrees , postoperative kyphosis of 44.3 degrees 
      and average correction of 39.3%. Analysis between the two groups showed
      statistically significant differences in the following variables: age (p = 0.02),
      postoperative kyphosis (p = 0.04) and degree and percentage of kyphosis
      correction (p = 0.001). There was no difference concerning preoperative kyphosis
      (p = 0.33). In the assessment of postoperative pain (VAS), the first group
      presented an average of 0.6, versus 0.5 in the second group. There were only
      minor complications: seven in the first group and two in the second. CONCLUSION:
      The two surgical techniques studied proved to be adequate for treating SK. In the
      present study, the deformity correction was greater in the first group, while the
      pain VAS results were better in the second group, with lower incidence of
      complications.

PMID- 27047832
TI  - EFFECT OF USE OF BONE-MARROW CENTRIFUGATE ON MUSCLE INJURY TREATMENT:
      EXPERIMENTAL STUDY ON RABBITS.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of bone-marrow
      centrifugate on the healing of muscle injuries in rabbits. METHODS: This
      experimental study involved use of fifteen adult male New Zealand White rabbits.
      Each animal received a transverse lesion in the middle of the right tibialis
      anterior muscle, to which an absorbable collagen sponge, soaked in a centrifugate
      of bone marrow aspirate from the ipsilateral iliac bone, was added. The left hind
      limb was used as a control and underwent the same injury, but in this case only
      the absorbable collagen sponge. Thirty days later, the animals were sacrificed to
      study the muscle healing. These muscle areas were subjected to histological
      analysis with histomorphometry, with the aim of measuring the number of muscle
      cells per square micrometer undergoing regeneration and the proportion of
      resultant fibrosis. RESULTS: The centrifugation method used in this study
      resulted in an average concentration of nucleated cells greater than the number
      of these cells in original aspirates, without causing significant cell
      destruction. Addition of the bone marrow centrifugate did not result in any
      significant increase in the number of muscle cells undergoing regeneration, in
      relation to the control group. There was also no significant difference in the
      proportion of resultant fibrosis, compared with the control group. CONCLUSION:
      Administration of the bone marrow centrifugate used in this study did not favor
      healing of muscle injuries in rabbits.

PMID- 27047833
TI  - PHYSICAL EXAMINATIONS FOR DIAGNOSING MENISCAL INJURIES: CORRELATION WITH SURGICAL
      FINDINGS.
AB  - OBJECTIVE: A set of five maneuvers for meniscal injuries (McMurray, Apley,
      Childress and Steinmann 1 and 2) was evaluated and their sensitivity,
      specificity, accuracy and likelihood were calculated. The same methods were
      applied to each test individually. METHODS: One hundred and fifty-two patients of
      both sexes who were going to undergo videoarthroscopy on the knee were examined
      blindly by one of five residents at this hospital, without knowledge of the
      clinical data and why the patient was going to undergo an operation. This
      examination was conducted immediately before the videoarthroscopy and its results
      were recorded in an electronic spreadsheet. The set of maneuvers was considered
      positive when one was positive. In the individual analysis, it was enough for the
      test to be positive. RESULTS: The analysis showed that the set of five meniscal
      tests presented sensitivity of 89%, specificity of 42%, accuracy of 75%, positive
      likelihood of 1.53 and negative likelihood of 0.26. Individually, the tests
      presented accuracy of between 48% and 53%. CONCLUSION: The set of maneuvers for
      meniscal injuries presented a good accuracy and significant value, especially for
      ruling out injury. Individually, the tests had less diagnostic value, although
      the Apley test had better specificity.

PMID- 27047834
TI  - LEG'S COMPARTMENT SYNDROME AFTER RECONSTRUCTION OF THE ANTERIOR CRUCIATE
      LIGAMENT: CASE REPORT.
AB  - The authors report a case of a patient that was submitted to a surgery of
      reconstruction of anterior cruciate ligament and collateral medial ligament
      repair of the left knee that complicated to a compartment syndrome. 

PMID- 27047835
TI  - SEGMENTAL CLAVICLE FRACTURE.
AB  - The aim here was to present an unusual case of segmental clavicle fracture
      associated with ipsilateral rib fracture. Although the clavicle is very
      superficial, undetected cases of both types of fracture may occur, because these
      patients usually suffer multiple trauma. The case of a patient with a fracture of
      the diaphysis and lateral extremity of the clavicle is described: the patient was
      treated surgically and an excellent result was achieved. Similar cases in the
      literature are reviewed and their management is discussed. 

PMID- 27047836
TI  - PROGRESSIVE OSSIFYING FIBRODYSPLASIA: CASE REPORT.
AB  - Progressive ossifying fibrodysplasia is a rare genetic disease that affects one
      individual in every two million births. Its main consequence is heterotopic
      ossification, i.e. formation of additional bone in abnormal locations. It is an
      autosomal dominant disease, usually caused by a new mutation in the ACVR1
      receptor gene, which is in the signaling pathway for bone morphogenic protein.
      This abnormality is not related to gender, ethnicity or consanguinity. The
      present study reports the case of A.C., a 17-year-old girl. Her clinical
      investigation began at the age of four years, but she was only diagnosed with FOP
      at the age of 15 years, after being evaluated by several specialists in different
      centers. The patient has two siblings, but her family history did not reveal any
      similar cases. 

PMID- 27047837
TI  - ACUTE LESION OF THE MOTOR BRANCH OF THE ULNAR NERVE IN THE WRIST AFTER TUG-OF-WAR
      TRAINING.
AB  - Papers correlating clinical and electrophysiological findings relating to ulnar
      nerve lesions in the wrist are uncommon in the literature, if compared with elbow
      injuries. We present the case of a patient with atrophy of the intrinsic
      musculature of the hand, secondary to injury only of the motor branch of the
      ulnar nerve, which is located in Guyon's canal close to the hamate hook. We
      review the anatomical, clinical and neurophysiological aspects of distal ulnar
      nerve injuries and we emphasize the importance of multidisciplinary approaches.
      Specifically in relation to the mechanism of injury of this patient (tug-of-war),
      we did not find any similar cases in the literature. We issue an alert regarding
      the risks during military physical training. 

PMID- 27047838
TI  - TIBIAL PERIPROSTHETIC FRACTURE COMBINED WITH TIBIAL STEM STRESS FRACTURE FROM
      TOTAL KNEE ARTHROPLASTY.
AB  - Total knee arthroplasty complications related to the prosthetic material are very
      rare, except for polyethylene wear. We report the case of a 58-year-old woman who
      came to the emergency service of our hospital with a periprosthetic tibial
      fracture (Mayo Clinic type I). Careful examination showed that this fracture was
      concomitantly associated with a tibial stem fatigue fracture. The prosthesis and
      the stem were sent to an independent biomechanics laboratory for evaluation. A
      finite-element CAD system was used to make a reconstruction, so as to ascertain
      whether there had been any manufacturing defect and what the causes of the event
      might have been. After evaluation of several hypotheses, it was concluded that
      the fracture in the prosthetic material had been caused by overloading at the
      plate/stem transition zone secondary to previous bone failure (fracture). From
      the evaluation of this case, the need to make appropriate assessment of bone
      mineralization can again be emphasized. In cases of doubt, a longer stem should
      be used. 

PMID- 27047839
TI  - CONGENITAL PSEUDARTHROSIS OF THE CLAVICLE.
AB  - Congenital pseudarthrosis of the clavicle (PCC) is a rare affection, that can be
      diagnosed at birth and represent a disturbance of union of the ossification
      centers. It's more common in girls and in the right side. This study objectives
      to proceed a revision about the subject, that was searched in online database of
      LILACS and MEDLINE. We found 56 articles till present data. Besides be a bit
      infrequent, the PCC must not be missed or even forgotten, especially as
      differential diagnosis with acute fracture of the clavicle at birth by trauma in
      the childbirth. The diagnostic is relatively easy and the treatment can be just
      observation or even surgical. 

PMID- 27047840
TI  - BILATERAL LUXATIO ERECTA, A CASE REPORT.
AB  - Inferior shoulder dislocation (luxactio erecta) is a rare lesion affecting
      approximately 0.5% of dislocations of this joint. The vast majority of these
      cases occur unilaterally. In September 2004, a 43 year old man was brought to the
      emergency room of the University Hospital of Santa Maria (HUSM) complaining of
      bilateral shoulder pain and inability to lower the arms, as a result of a fall
      with the arms abducted, while carrying out work activities. After physical
      examination and radiological exams, it was found that the patient had a bilateral
      inferior shoulder dislocation. He was referred to the surgical ward and after
      intravenous sedation, both shoulders were reduced by closed reduction using the
      traction-countertraction maneuver. The patient was discharged the day after the
      reduction. Both arms were immobilized with a velpeau sling in total adduction and
      intrarotation, with instructions to maintain immobilization for three weeks. The
      patient was also advised to receive physiotherapy. 

PMID- 27047841
TI  - LIPOSARCOMA OF THE KNEE IN A TENNIS PLAYER: CASE REPORT.
AB  - Liposarcoma is an uncommon malignant tumor. It originates in the mesenchymal
      cells, and is the most common of the soft tissue sarcomas. The authors report a
      case of a 40 year-old male tennis player with liposarcoma in the posterior right
      knee and distal thigh region. 

PMID- 27047842
TI  - The difficult art of publishing.

PMID- 27047843
TI  - LATERAL EPICONDYLITIS OF THE ELBOW.
AB  - Lateral epicondylitis, also known as tennis elbow, is a common condition that is
      estimated to affect 1% to 3% of the population. The word epicondylitis suggests
      inflammation, although histological analysis on the tissue fails to show any
      inflammatory process. The structure most commonly affected is the origin of the
      tendon of the extensor carpi radialis brevis and the mechanism of injury is
      associated with overloading. Nonsurgical treatment is the preferred method, and
      this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma
      injections and use of specific immobilization. Surgical treatment is recommended
      when functional disability and pain persist. Both the open and the arthroscopic
      surgical technique with resection of the degenerated tendon tissue present good
      results in the literature. 

PMID- 27047844
TI  - REHABILITATION PROTOCOL AFTER ISOLATED POSTERIOR CRUCIATE LIGAMENT
      RECONSTRUCTION.
AB  - To create a rehabilitation protocol following reconstruction of the posterior
      cruciate ligament (PCL), through a literature review. The literature review was
      conducted in the Medline and Embase databases, to search for data on
      biomechanical concepts and analyses relating to the posterior cruciate ligament
      of the knee. The search strategy was set up using the following rules: problem or
      injury in association with anatomical location terms; or surgical intervention
      procedure in association with rehabilitation terms. We began the process in this
      manner and subsequently introduced restrictions on certain terms to improve the
      search specificity. To design the protocol, a table was created for better data
      assessment, based on the time that elapsed between surgery and the start of
      physiotherapy. A rehabilitation protocol was created to improve weight-bearing
      control in the initial weeks after surgery, with the aid of a knee brace. Our aim
      was to achieve gains in total range of motion of the knee, which should be
      attained by the third month, thereby avoiding contractures resulting from the
      tissue healing process. Strengthening exercises and sensory-motor training were
      guided accordingly, thus avoiding overload on the graft and respecting the
      healing phases. The protocol proposed through this review was based on the
      current evidence relating to this subject. 

PMID- 27047845
TI  - ANALYSIS ON THE VARIATION OF MEDIAL ROTATION VALUES ACCORDING TO THE POSITION OF
      THE HUMERAL DIAPHYSIS.
AB  - OBJECTIVE: To analyze the validity of measurements of medial rotation (MR) of the
      shoulder, using vertebral levels, according to the variation in the position of
      the humeral diaphysis, and to test the bi-goniometer as a new measuring
      instrument. METHODS: 140 shoulders (70 patients) were prospectively evaluated in
      cases presenting unilateral shoulder MR limitation. The vertebral level was
      evaluated by means of a visual scale and was correlated with the angle obtained
      according to the position of the humeral diaphysis, using the bi-goniometer
      developed with the Department of Mechanical Engineering of Mackenzie University.
      RESULTS: The maximum vertebral level reached through MR on the unaffected side
      ranged from T3 to T12, and on the affected side, from T6 to the trochanter.
      Repositioning of the affected limb in MR according to the angular values on the
      normal side showed that 57.13% of the patients reached lower levels, between the
      sacrum, gluteus and trochanter. From analysis on the maximum vertebral level
      attained and the variation between the affected angle x (frontal plane: abduction
      and MR of the shoulder) and the unaffected angle x in MR, we observed that the
      greater the angle of the diaphyseal axis was, the lower the variation in the
      vertebral level attained was. From evaluating the linear correlation between the
      variables of difference in maximum vertebral level reached and variation in the
      affected angle y (extension and abduction of the shoulder) and the unaffected
      angle y in MR, we observed that there was no well-established linear relationship
      between these variables. CONCLUSION: Measurement of MR using vertebral levels
      does not correspond to the real values, since it varies according to the
      positioning of the humeral diaphysis.

PMID- 27047846
TI  - ARTHROSCOPIC REPAIR OF SMALL AND MEDIUM TEARS OF THE SUPRASPINATUS MUSCLE TENDON:
      EVALUATION OF THE CLINICAL AND FUNCTIONAL OUTCOMES AFTER TWO YEARS OF FOLLOW-UP.
AB  - OBJECTIVE: To evaluate the clinical and functional outcomes from arthroscopic
      repairs on small and medium-sized tears of the supraspinatus muscle tendon.
      METHODS: 129 cases of isolated small and medium tears of the supraspinatus muscle
      tendon were evaluated retrospectively. The average duration of pain was 29
      months. The average joint range of motion comprised active elevation of 136
      degrees , lateral rotation of 58 degrees  and medial rotation at T12 level; and
      the preoperative functional UCLA score averaged 17 points. In all the cases,
      complete repair could be achieved. RESULTS: The average score on the UCLA
      functional scale in the postoperative period was 32 points. The average length of
      follow-up was 39 months. Seventy-five cases (58%) had excellent results and 42
      (32%) had good results. The average final active elevation was 156 degrees  with
      an average gain of 20 degrees , and the average final lateral rotation was 57
      degrees  with an average gain of 9 degrees . Both of these were statistically
      significant (P < 0.05). The patients who underwent tenotomy of the long head of
      the biceps (LHB), with or without tenodesis, did not present statistically
      inferior functional outcomes, in comparison with the patients who only underwent
      decompression and lesion repair (P = 1.00). Fourteen cases (10.8%) presented
      complications during the postoperative period. Six (4.6%) developed adhesive
      capsulitis and four (3.1%) presented re-rupture of the tendon, proven by means of
      magnetic resonance imaging. CONCLUSIONS: Arthroscopic repair of small and medium
      tears of the supraspinatus muscle tendon provided a functional clinical
      improvement, with good and excellent results in 90% of the cases.

PMID- 27047847
TI  - ASSESSMENT OF TIBIAL SLOPE ANGLE AND PATELLAR HEIGHT AFTER MEDIAL-OPENING TIBIAL
      OSTEOTOMY.
AB  - OBJECTIVE: To measure the variation in posterior tibial slope angle and patellar
      height in patients who underwent proximal tibial valgus-producing osteotomy using
      the medial-opening wedge technique. METHODS: Anteroposterior panoramic
      radiographs of the lower limbs and lateral radiographs of the knee obtained
      before and after tibial valgus-producing osteotomy on 46 patients with
      unicompartmental arthrosis of the knee were analyzed. RESULTS: In 23 patients, an
      external fixator was used to gradually apply a medial-opening wedge; and in the
      other 23, a blocked plate with a stop bar was applied as a fixation method.
      Patients with tricompartmental knee disease and those who underwent osteotomy to
      treat fracture sequelae were excluded from this study. After surgery, the mean
      increase in the tibial slope was 1.7 degrees (p < 0.01) in the group in which the
      blocked plate with a stop bar was used; and 2.7 degrees (p < 0.05) in the group
      in which the external fixator was used. There was no statistical difference
      between the groups regarding the increase in the posterior tibial slope.
      CONCLUSION: The patellar height did not present any change in the cases in which
      the plate was used, when measured using the Insall-Salvati method, but it
      presented a decrease in 11 cases (47.8%) when the Caton-Deschamps method was
      applied. The same tendency was observed regarding change in the patellar height
      in the cases in which the external fixator was used, such that a decrease was
      observed in eight cases (34.7%) only when measured using the Caton-Deschamps
      method.

PMID- 27047848
TI  - EWING'S SARCOMA: EPIDEMIOLOGY AND PROGNOSIS FOR PATIENTS TREATED AT THE PEDIATRIC
      ONCOLOGY INSTITUTE, IOP-GRAACC-UNIFESP.
AB  - OBJECTIVE: To outline the epidemiological profile and prognosis for Ewing's
      sarcoma in the Brazilian population. MATERIAL AND METHODS: The medical records of
      64 patients with intraosseous Ewing's sarcoma who were treated at the Pediatric
      Oncology Institute, IOP-GRAACC-Unifesp, between 1995 and 2010, were
      retrospectively evaluated. RESULTS: The statistical analysis on the data obtained
      did not correlate factors such as sex, trauma, pathological fracture and time
      taken for case diagnosis with the treatment outcome. Factors such as initial
      metastasis, lung metastasis, tumor site, age, recurrence and type of surgery
      showed results corroborating what has been established in the literature.
      CONCLUSION: The prognosis in cases of Ewing's sarcoma was mainly influenced by
      the presence of metastases at the time of diagnosis.

PMID- 27047849
TI  - EVALUATION OF UPPER-LIMB FUNCTION IN PATIENTS WITH OBSTETRIC PALSY AFTER MODIFIED
      SEVER-L'EPISCOPO PROCEDURE.
AB  - OBJECTIVE: To evaluate upper-limb function by means of the Mallet score, in
      patients with medial rotation contracture of the shoulder who underwent the
      modified Sever-L'Episcopo procedure, and to correlate evolution with age and
      length of postoperative follow-up. METHODS: Sixteen patients were assessed by
      comparing the pre and postoperative Mallet scores and correlating the differences
      between these scores with age at the time of surgery and length of follow-up.
      RESULTS: A statistically significant improvement in the postoperative Mallet
      score was observed. The correlations of the differences in scores with age and
      length of follow-up were not statistically significant. CONCLUSION: The modified
      Sever-L'Episcopo procedure led to improved upper-limb function according to the
      Mallet score. Limb function did not present correlations with age or length of
      follow-up.

PMID- 27047850
TI  - SAFE LOCALIZATION FOR PLACEMENT OF PERCUTANEOUS PINS IN THE CALCANEUS.
AB  - OBJECTIVE: To determine the areas presenting risk in six zones of the calcaneus,
      and to quantify the risks of injury to the anatomical structures (artery, vein,
      nerve and tendon). METHOD: Fifty-three calcanei from cadavers were used, divided
      into three zones and each subdivided in two areas (upper and lower) by means of a
      longitudinal line through the calcaneus. The risk of injury to the anatomical
      structures in relation to each Kirschner wire was determined using a graded
      system according to the Licht classification. The total risk of injury to the
      anatomical structures through placement of more than one wire was quantified
      using the additive law of probabilities and the product law for independent
      events. RESULTS: The injury risk calculation according to the Licht
      classification showed that the highest risk of injury to the artery or vein was
      in zone IA (43%), in relation to injuries to nerves and tendons (13% and 0%,
      respectively). CONCLUSION: This study made it possible to identify the most
      vulnerable anatomical structures and quantify the risk of injury to the
      calcaneus.

PMID- 27047851
TI  - ELIGIBILITY FOR THE HIP-RESURFACING ARTHROPLASTY PROCEDURE: AN EVALUATION ON 592
      HIPS.
AB  - OBJECTIVE: To investigate the percentage of ideal patients who would be eligible
      for hip-resurfacing surgery at a reference service for hip arthroplasty. METHODS:
      Out of all the cases of hip arthroplasty operated at Hospital do Servidor Publico
      Estadual de Sao Paulo (HSPE) between January 2009 and December 2010, we assessed
      a total of 592 procedures that would fit the criteria for indication for
      resurfacing arthroplasty, after clinical and radiological evaluation according to
      the criteria established by the Food and Drug Administration (FDA) and by Seyler
      et al. RESULTS: Among the total number of hip replacement arthroplasty cases,
      5.74% of the patients were eligible. Among the patients who underwent primary
      arthroplasty, we found that 8.23% presented ideal conditions for this procedure.
      CONCLUSION: The study demonstrated that this type of surgery still has a limited
      role among hip surgery methods.

PMID- 27047852
TI  - TIBIOTALOCALCANEAL ARTHRODESIS WITH LATERAL COMPRESSION PLATE: ARTRODESE TIBIO
      TALO-CALCANEANA COM PLACA DE COMPRESSAO LATERAL.
AB  - OBJECTIVE: The objective of this study was to evaluate the short-term clinical
      and radiographic results from a TTC fusion procedure using a lateral locking
      plate specifically designed for this purpose. METHODS: All the fourteen patients
      were evaluated using a variety of methods, including a visual analogue scale
      (VAS), the AOFAS hindfoot score and a subjective satisfaction scale. The average
      follow-up was 10 months. RESULTS: The average AOFAS score improved from 41 points
      preoperatively to 63 points postoperatively. The VAS pain score decreased from 7
      to 3 points. Four patients reported excellent results, eight good, one fair and
      one poor. CONCLUSION: Our study provides support for using a specially designed
      plate for TTC fusion in hindfoot salvage surgery. RESUMO: Objetivo: O proposito
      deste estudo e avaliar os resultados clinicos e radiologicos a curto prazo do
      procedimento de fusao tibio-talo-calcaneana (TTC) com o uso de uma placa lateral
      bloqueada especificamente concebida para este fim. Metodos: Todos os 14 pacientes
      foram avaliados usando uma variedade de metodos, incluindo a escala analogico
      visual da dor (EAV), escore da AOFAS para o retrope e escala subjetiva de
      satisfacao. O acompanhamento medio foi de 10 meses. Resultados: O escore AOFAS
      medio melhorou de 41 pontos no periodo pre-operatorio para 63 pontos no periodo
      pos-operatorio. O escore da dor (EAV) caiu de 7 para 3 pontos. Quatro
      pacientesforam classificados como excelentes resultados, oito bons, um moderado e
      um ruim. Conclusao: Nosso estudo da suporte ao uso da placa especialmente
      desenhada para a fusao tibio-talo-calcaneana (TTC) nas cirurgias de salvamento do
      retrope.

PMID- 27047853
TI  - THORACOLUMBAR BURST FRACTURE: CORRELATION BETWEEN KYPHOSIS AND FUNCTION AFTER
      SURGICAL TREATMENT.
AB  - OBJECTIVE: To assess the correlation between post-traumatic kyphosis in patients
      with thoracolumbar burst fractures undergoing surgical treatment and the
      functional result from treatment. METHODS: A retrospective study was conducted on
      27 patients with thoracolumbar burst fractures according to Denis and A3 to
      Margerl's classification who met the inclusion criteria for this sample and
      underwent surgical treatment with a minimum follow-up of six months. The
      patients' mean age was 46.96, with a range from 16 to 73 years. The treatment
      outcome was evaluated based on applying the short-form 36 (SF-36) quality of life
      questionnaire, Denis pain and work scale and visual pain scale. The kyphosis was
      measured according to the Cobb method at the end of the follow-up. RESULTS: The
      residual kyphosis was found not to correlate with the SF-36, Denis pain and work
      scale or visual pain score (p > 0.05). CONCLUSION: There is no correlation
      between the final clinical result and residual kyphosis in patients with
      thoracolumbar burst fractures who undergo surgical treatment.

PMID- 27047854
TI  - CALCIFYING TENDINOPATHY: A LOCAL OR A SYSTEMIC CONDITION?
AB  - OBJECTIVE: To evaluate the relationship between cases of calcifying tendinopathy
      of the shoulder and symptomatic metabolic diseases such as kidney stones,
      gallstones and gout. METHODS: Calcifying tendinopathy of the shoulder was
      diagnosed in 63 patients between May 2007 and September 2011. All the patients
      were treated by the same orthopedic surgeon and were interviewed to gather the
      following data: age at diagnosis, sex, affected side, dominant side, body mass
      index (BMI), smoking status and previous histories of kidney stones, gallstones
      or gout. For statistical analysis, a control group of 63 patients with similar
      demographic characteristics was used. RESULTS: Among the 63 patients with
      calcifying tendinopathy of the shoulder, 35 (56%) were male. The right side was
      affected in 38 patients (60%) and the average age was 48.2 years. Thirty-one
      patients (49%) had histories involving some of the metabolic diseases
      investigated: 20 patients (32%) reported kidney stones, six (9.5%) gallstones,
      four (6.3%) gout and one (2%) concurrent diagnoses of kidney stones and gout. In
      the control group, eleven patients (17%) had histories involving some of the
      metabolic diseases investigated: six patients (9.5%) reported kidney stones, four
      (6.3%) gallstones and one (1.6 %) gout. CONCLUSIONS: The high frequency of
      nephrolithiasis in patients with calcifying tendinopathy of the shoulder in our
      study suggests that there are common mechanisms in the pathophysiology of these
      disorders. Better understanding of these diseases may enable improvement of
      diagnostics and treatments.

PMID- 27047855
TI  - SUCCESS OF CONSERVATIVE TREATMENT OF TRIGGER THUMB IN CHILDREN AFTER MINIMUM
      FOLLOW-UP OF FIVE YEARS.
AB  - OBJECTIVE: The aim of this study was to evaluate the outcome of conservative
      treatment of trigger thumb in children, in order to discuss the real need for
      surgical release in these patients. METHODS: This was a retrospective study on a
      group of children with trigger thumb who were treated conservatively by the same
      orthopedic surgeon with gentle manipulation at the time of the consultation and
      guidance on stretching to be performed at home. The cases were followed up for at
      least five years. RESULTS: Thirteen thumbs in 11 children (seven boys and four
      girls) were treated. The mean age at the first consultation was 26.3 months
      (range: 11 to 36 months). The mean follow-up was 10 years (range: 5 to 16 years).
      Ten thumbs showed satisfactory results (77%): eight of these were diagnosed when
      the child was younger than two years of age. The mean time taken from diagnosis
      to clinical improvement was 20.8 months (range: 6 to 36 months). The three thumbs
      that required surgical treatment were diagnosed after the age of two years and
      six months. CONCLUSIONS: Conservative treatment of trigger thumb in children
      showed a high rate of success, especially in children who were diagnosed up to
      the age of two years. This is important information to be passed on to parents
      and may avoid unnecessary surgery in many cases.

PMID- 27047856
TI  - SURGICAL TREATMENT FOR FEMOROACETABULAR IMPINGEMENT IN A GROUP THAT PERFORMS
      SQUATS.
AB  - OBJECTIVE: Describe the results from arthroscopic surgical treatment on a group
      of patients who developed symptoms after repetitive physical activity of moving
      their hips in a position of hyperflexion, as in leg presses and squats. METHODS:
      The study group comprised 47 individuals (48 hips) who developed the onset of
      painful symptoms associated with hip hyperflexion exercises (leg presses or
      squats) and underwent arthroscopic treatment. The patients were evaluated
      radiographically and clinically according to the "Harris Hip Score", as modified
      by Byrd (MHHS), pre and postoperatively, and were asked about their return to
      sports activities and the surgical findings. RESULTS: The mean preoperative and
      postoperative MHHS, respectively, were 60 points (SD 11.0, range 38.5 to 92.4)
      and 95.9 points (SD 7.7, range 63.8 to 100), with an increase of 35.9 points (P <
      0.001). Regarding physical activity, 30 individuals (71.5%) resumed sports
      activities after surgery, and 25 of them (83.4%) at the previous level. Six
      patients (12.8%) did not resume activities because of persistent pain. During
      arthroscopy, 48 hips (100%) presented lesions of the acetabular labrum, and 41
      hips (85.4%) had acetabular chondral lesions. CONCLUSION: The patients with
      painful symptoms after hip hyperflexion exercises associated with
      femoroacetabular impingement presented improvements after arthroscopic treatment.

PMID- 27047857
TI  - EFFECT OF THE GRAFTING SECTION AREA ON ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION
      SURGERY - HISTOLOGICAL STUDY ON DOGS.
AB  - OBJECTIVE: To correlate the initial grafting section area with the outcomes from
      anterior cruciate ligament (ACL) reconstruction surgery. Eight dogs underwent
      operations, divided into two groups according to graft size: Group A, 25% and
      Group B, 40% of the patellar ligament (PL) width. METHODS: After eight months,
      the dogs were sacrificed for macroscopic and histological analysis on the
      reconstructed ligaments. Each dog's contralateral knee was used as a control.
      RESULTS: In both groups, all the reconstructed ligaments were seen to be viable
      and hypertrophied. The morphology of the PL grafting had changed, which was
      observed by measuring the crimp and cellularity, and it resembled that of the
      ACL. CONCLUSION: The grafting section area did not influence the histological
      outcomes from ACL reconstruction surgery in dogs.

PMID- 27047858
TI  - ANALYSIS ON QUALITY OF LIFE OF PATIENTS WITH OSTEOARTHROSIS UNDERGOING TOTAL HIP
      ARTHROPLASTY.
AB  - OBJECTIVE: The aim of the study was to evaluate the health-related quality of
      life among patients affected by hip osteoarthrosis who were treated by means of
      total hip arthroplasty. METHODS: A cohort of 38 patients operated by a single
      surgeon in a regional referential teaching hospital during the year 2010 was
      prospectively studied and followed up for at least six months until they had
      achieved satisfactory rehabilitation. Each patient gave responses to the SF-36
      form immediately before the operation and six months later and the Harris Hip
      Score was obtained at the same time. The pre and postoperative results were
      analyzed and compared with the literature. RESULTS: The pre and postoperative SF
      36 results were as follows: physical function: 13.4-53.7; role physical: 9.21
      48.0; body pain: 23.1-62.6; general health: 54.2-71.3; vitality: 40.3-69.9;
      social function: 40.8-74.3; role emotional: 23.7-64.9; and mental health: 52.6
      80.4. The Harris Hip Score went from 36.1 to 92.1, on average. All the results
      were statistically significant (p < 0.001). CONCLUSIONS: The combination of two
      scales was shown to be valuable in identifying bias and gave greater reliability
      for understanding the different variables. The study showed that there was a
      significant improvement in health-related quality of life among patients affected
      by osteoarthrosis of different etiologies who underwent total hip arthroplasty.
      Health-related quality of life evaluations cannot replace clinical evaluations
      provided by specific instruments and physicians' experience but can add important
      data through giving value to patients' sets of expectations regarding medical
      treatment. Moreover, such evaluations can be considered to be an efficient tool
      for analyzing the outcomes from total hip arthroplasty.

PMID- 27047859
TI  - COMPARATIVE STUDY ON USE OF PLATELET-RICH PLASMA ALONE AND IN COMBINATION WITH
      ALPHA-TRICALCIUM PHOSPHATE CEMENT FOR BONE REPAIR IN RATS.
AB  - OBJECTIVES: To evaluate the effect of alpha-tricalcium phosphate (alpha-TCP)
      cement combined with platelet-rich plasma (PRP) on osteogenesis, and to compare
      the results with use of PRP alone. METHODS: A bilateral defect was produced in
      rat femurs and was filled with one of two types of treatments (PRP or alpha-TCP +
      PRP). The outcomes were evaluated after four and eight weeks. Radiographic images
      provided values for the lesion area, and histology (picrosirius staining)
      indicated the area of new bone formation. RESULTS: The means relating to the
      lesion area of the alpha-TCP + PRP group (2.64 +/- 2.07 and 1.91 +/- 0.93 mm(2),
      after four and eight weeks, respectively) showed numerically better but non
      significant results (p > 0.05) than those seen in the PRP group (5.59 mm 2 +/-
      2.69 and 3.23 +/- 1.46 mm 2, after four and eight weeks, respectively). The mean
      new bone formation rates were 62.7% +/- 12.1 and 79.01% +/- 6.25 in the PRP
      group, and 73.3% +/- 12.7 and 85.86% +/- 10.45 in alpha-TCP + PRP group, after
      four and eight weeks, respectively (p > 0.05). CONCLUSION: The data from this
      study suggest that treatment with alpha-TCP cement combined with PRP does not
      show any significant difference in comparison with PRP alone. However, there is a
      possible early effect on bone regeneration when the two biomaterials are applied
      together.

PMID- 27047860
TI  - PSEUDARTHROSIS OF THE TUBERCLE OF THE SCAPHOID BONE IN IMMATURE SKELETON: CASE
      REPORT.
AB  - The aim of this study was to present a case report on pseudarthrosis of the
      scaphoid tubercle, a pathological condition that affects the young and active
      population. This entity often develops as a result of failure to make an early
      diagnosis and a late start to treatment. This report describes the case of a 15
      year-old patient with a history of a neglected fracture of the scaphoid tubercle
      that occurred one year earlier and evolved to pseudarthrosis of the tubercle,
      which is an unusual location for this type of complication. The diagnosis was
      made from the clinical history and radiographic examination. The treatment was
      undertaken in accordance with the Matti-Russe technique, by means of a volar
      route, thus avoiding injury to the scaphoid vascularization, with good clinical
      and radiographic evolution. Pseudarthrosis of the scaphoid tubercle is a rare
      condition resulting from a fracture in an unusual location in the scaphoid bone,
      and it is important because it affects the young and active population. The
      correct diagnosis is only rarely made by radiologists or surgeons at the time of
      the fracture, because of failure to recognize this entity. This mistake delays
      and causes difficulty in treatments for the complications resulting from this
      kind of fracture. Therefore, it is essential to include this condition in
      differential diagnoses in order to avoid mistaken conduct. The treatment chosen
      was shown to be an effective option in this specific case. 

PMID- 27047861
TI  - LIPOMA ARBORESCENS: RARE CASE OF ROTATOR CUFF TEAR ASSOCIATED WITH THE PRESENCE
      OF LIPOMA ARBORESCENS IN THE SUBACROMIAL-SUBDELTOID AND GLENOHUMERAL BURSA.
AB  - Lipoma arborescens is a rare intra-articular disease that is usually
      monoarticular and is characterized by extensive proliferation of the synovial
      villi and hyperplasia of the subsynovial fat. The synovial tissue is
      progressively replaced by mature fat cells in the synovial membrane. The present
      study reports a case of a rare condition of lipoma arborescens that was
      simultaneously intra-articular (glenohumeral joint) and in the subacromial
      subdeltoid bursa, in association with a torn supraspinatus tendon. The clinical,
      histological and radiographic presentations and treatment are discussed here. The
      description of this case includes radiographic and magnetic resonance evaluations
      and pathological examination. Although lipoma arborescens is a rare condition, it
      should be taken into consideration in cases presenting synovial
      hyperproliferation and synovial fat replacement. 

PMID- 27047862
TI  - FRACTURE-DISLOCATION OF THE THORACIC SPINE DURING SECOND TRIMESTER OF PREGNANCY:
      CASE REPORT AND LITERATURE REVIEW.
AB  - Spinal fractures associated with spinal cord injury rarely affect pregnant
      patients. The authors present the case of a 20-year-old woman in her 20(th) week
      of pregnancy, who suffered fracture-dislocation of the thoracic spine (T4-T5) and
      underwent decompression, reduction and posterior fusion with pedicle screws.
      Despite the complete spinal cord injury presented, the pregnancy progressed
      uneventfully and resulted in birth via normal delivery of a healthy newborn at
      term. Some particular features of this case, like the care needed in using
      ionizing radiation, the surgical approach and delivery, use of steroids and
      pregnancy complications in such patients are discussed here. Only a
      multidisciplinary team composed by physicians from different specialties (spinal
      surgeons, obstetricians and physiatrists), nurses and physiotherapists is capable
      of assisting pregnant patients with spinal cord injuries satisfactorily. 

PMID- 27047863
TI  - Information without barriers: a risk for patients.

PMID- 27047864
TI  - CONGENITAL DEFORMITIES OF THE UPPER LIMBS.: PART I: FAILURE OF FORMATION.
AB  - This article, divided into three parts, had the aims of reviewing the most common
      upper-limb malformations and describing their treatments. In this first part,
      failure of formation is discussed. The bibliography follows after the first part.

PMID- 27047865
TI  - OSTEOCHONDRITIS DISSECANS OF THE KNEE: DIAGNOSIS AND TREATMENT.
AB  - Osteochondritis dissecans (OCD) is a pathological process affecting the
      subchondral bone of the knee in children and adolescents with open growth plates
      (juvenile OCD) and young adults with closed growth plates (adult OCD). It may
      lead to secondary effects on joint cartilage, such as pain, edema, possible
      formation of free bodies and mechanical symptoms, including joint locking. OCD
      may lead to degenerative changes may develop if left untreated. This article
      presents a review and update on this problem, with special emphasis on diagnosis
      and treatment. The latter may include either conservative methods, which show
      more predictable results for juvenile OCD, or various surgical methods, which
      include reparative techniques like isolated removal of the fragment, bone
      drilling and fixation of the osteochondral fragments, and restorative techniques
      like microfractures, autologous osteochondral transplantation (mosaicplasty),
      autologous chondrocyte implantation and fresh osteochondral allograft, depending
      on lesion stability, lesion viability, skeletal maturity and OCD process
      location. Recent assessments on the results from several types of treatment have
      shown that there is a lack of studies with reliable levels of evidence and have
      suggested that further multicenter prospective randomized and controlled studies
      on management of this disease should be conducted. 

PMID- 27047866
TI  - POSTEROSUPERIOR SURGICAL ACCESS ROUTE FOR TREATMENT OF ACROMIOCLAVICULAR
      DISLOCATIONS: RESULTS FROM 84 SURGICAL CASES.
AB  - OBJECTIVE: To evaluate the results from surgical treatment of 84 cases of acute
      acromioclavicular dislocation, using a posterosuperior access route. METHODS:
      Eighty-four cases of acute acromioclavicular dislocation (grade III in the Allman
      Tossy classification) operated between November 2002 and May 2010 were evaluated.
      The patients' mean age was 34 years. The diagnoses were made using clinical and
      radiographic evaluations. The patients were operated by the same surgical team,
      within three weeks of the date of the trauma, using a posterosuperior approach to
      the shoulder to access the top of the base of the coracoid process for placement
      of two anchors, which were used in reducing the dislocation. The minimum follow
      up was 12 months. The postoperative clinical-radiographic evaluation was done
      using the modified Karlsson criteria and the University of California at Los
      Angeles (UCLA) score. RESULTS: 92.8% of the 84 patients treated presented good or
      excellent results, and 7.2% presented fair or poor results, using the UCLA
      assessment score. According to the modified Karlsson criteria, 76.2% were
      assessed as grade A, 17.9% as grade B and 5.9% as grade C. CONCLUSION: The
      posterosuperior access route to the shoulder is a new option for accessing the
      coracoid process and treating acromioclavicular dislocation, with clinical and
      radiographic results equivalent to those in the literature.

PMID- 27047867
TI  - EVALUATION OF THE COMPLICATIONS OF SURGICAL TREATMENT OF FRACTURES OF THE
      PROXIMAL EXTREMITY OF THE HUMERUS USING A LOCKING PLATE.
AB  - OBJECTIVE: To evaluate the complications from surgical treatment using a locking
      plate among patients with fractures of the proximal extremity of the humerus.
      METHODS: Between July 2004 and December 2009, 56 patients with fractures of the
      proximal extremity of the humerus were treated using the PHILOS((r)) plate. There
      were 19 male patients and 37 female patients, with a mean age of 62 years (range:
      30 to 92 years). All the cases had a mean postoperative followup period of 12
      months. Thirteen fractures were classified as presenting in two parts, 28 as
      three, eight as four and seven as epiphyseal fractures. RESULTS: Among the
      patients operated, 26 were considered to have achieved excellent results, twelve
      good, ten fair and eight poor, according to the UCLA score. Thirty complications
      occurred in 20 patients (35.7%), among which the most frequent complication was
      inadequate reduction of the fracture, which occurred in eight cases. Subacromial
      impact, caused by the plate, occurred in seven cases, while inadequate fixation
      occurred in six cases. Other complications such as pseudarthrosis, adhesive
      capsulitis, avascular necrosis, loss of varus reduction and infection were also
      seen. CONCLUSION: The functional results from treating fractures of the proximal
      extremity of the humerus using a locking plate depended on correct anatomical
      reduction of the fracture and stable fixation of the implant. Complications still
      occur frequently, particularly because of intraoperative technical difficulty,
      fracture severity and possible inexperience of the surgeon.

PMID- 27047868
TI  - UNSTABLE FEMORAL FRACTURES TREATED WITH TITANIUM ELASTIC INTRAMEDULLARY NAILS, IN
      CHILDREN.
AB  - OBJECTIVE: To evaluate the indications, epidemiology, associated lesions,
      complications and prognosis among children with unstable femoral diaphysis
      fractures who were treated with titanium elastic intramedullary nails. METHOD:
      This was a retrospective analysis on 24 patients aged 5-12 years with unstable
      femoral diaphysis fractures who underwent surgical treatment with elastic
      titanium intramedullary nails at the Cajuru University Hospital, Curitiba-PR,
      between April 2002 and March 2008, with a minimum follow-up of 36 months. The
      epidemiological data, angular deviations, leg shortening and bone consolidation
      were evaluated. RESULTS: The medical files of 113 cases operated between April
      2002 and March 2008 were reassessed. From these, 24 cases of unstable femoral
      diaphysis fractures treated with elastic titanium intramedullary nails with
      retrograde insertion were included in the study. There were two bilateral
      fractures and two exposed fractures. Seven patients were female and 17 were male,
      and the mean age was 8.3 years. The following were presented at the end of the
      study: shortening, varus or valgus displacement, final retrocurvatum or
      antecurvatum of zero, and absence of delayed consolidation or pseudarthrosis.
      CONCLUSIONS: The elastic titanium intramedullary nails were easily placed and
      removed. We believe that using elastic titanium intramedullary nails is a good
      option for fixation of unstable femoral fractures in children.

PMID- 27047869
TI  - ISOKINETIC AND FUNCTIONAL EVALUATION OF DISTAL BICEPS RECONSTRUCTION USING THE
      MAYO MINI-DOUBLE ROUTE TECHNIQUE.
AB  - OBJECTIVE: To evaluate the functional outcome among patients with distal biceps
      injuries who were operated using the Mayo mini-double route technique, with a
      minimum follow-up of six months after surgery, through digital isokinetic
      dynamometry, goniometry and subjective scores in order to establish objective and
      subjective improvement patterns and discuss the effectiveness of the procedure.
      METHODS: Nine patients who underwent surgery to treat distal biceps injury were
      evaluated by means of Cybex digital dynamometry using an angular velocity of 30
      degrees /s with five repetitions and 120 degrees /s with 15 repetitions, in
      comparison with the uninjured side. DASH (Disabilities of the arm, shoulder and
      hand), Mayo elbow score and conventional goniometry were also used. RESULTS:
      Digital dynamometer showed that using the angular velocity of 30 degrees /s with
      five repetitions, there was an average flexion deficit of 9.6% and an average
      supination deficit of -28.97%. Using an angular velocity of 120 degrees /s with
      fifteen repetitions, the average flexion deficit was 4.43% and the average
      supination deficit was -24.1%. CONCLUSIONS: The loss of flexion followed the
      pattern already shown in the literature. However, in our series, there were
      supination strength gains, possibly due to the strict rehabilitation protocol.
      The technique used in this study was safe and low-cost, with few complications
      and good functional results.

PMID- 27047870
TI  - CLINICAL DIAGNOSIS OF SUBSCAPULARIS TENDON TEAR USING THE BEAR HUG SEMIOLOGICAL
      MANEUVER.
AB  - OBJECTIVE: To evaluate the Bear Hug maneuver for clinically diagnosing
      subscapularis tendon tears, and compare this with other maneuvers described
      previously (Lift-off, Napoleon and Belly Press). METHODS: Forty-nine patients
      with rotator cuff injuries who had undergone arthroscopy to repair the injury and
      had previously been assessed using the semiological maneuvers mentioned above
      were evaluated. RESULTS: The diagnostic values obtained for the Bear Hug test
      were as follows: sensitivity 75%, specificity 56%, positive predictive value 62%,
      negative predictive value 70% and accuracy 65%. CONCLUSION: The highest
      sensitivity and negative predictive value values were obtained with the Bear Hug
      test. The highest specificity value was seen with the Lift-off test. The Belly
      press test gave the greatest specificity, positive predictive and accuracy
      values.

PMID- 27047871
TI  - COMPARATIVE ANALYSIS ON MUSCLE STRENGTH AMONG PATIENTS WHO UNDERWENT ARTHROSCOPIC
      TENOTOMY OF THE LONG HEAD OF THE BICEPS IN RELATION TO ESTHETIC DEFORMITY.
AB  - OBJECTIVE: To determine whether there was any discrepancy in elbow flexion
      strength among patients with and without evident clinical deformity resulting
      from arthroscopic tenotomy on the long head of the biceps. METHOD: A group of 120
      patients who underwent this procedure were evaluated. After applying the
      exclusion criteria, 89 patients remained in the analysis. Eighteen months after
      the operation (median), the elbow flexion strength was measured in newtons using
      a digital dynamometer. Three consecutive measurements were made and the average
      was used. The dominant and non-dominant sides were compared. Sex, age and mean
      elbow flexion strength in the operated and contralateral arms of patients with
      and without apparent clinical deformity were evaluated. RESULTS: The median elbow
      flexion strength among the patients with evident clinical deformity was 17.78 N
      for the dominant arm and 20.87 N for the non-dominant arm. The difference was
      2.51 N. In the group without evident clinical deformity, the difference was 2.14
      N. The median muscle strength in the operated arm was 17.26 N, while the median
      was 20.06 N in the non-operated arm, thus suggesting that there was a significant
      loss of muscle strength (p = 0.005). The difference in muscle strength loss
      between the patients with and without evident deformity was not considered
      statistically significant (p = 0.977). CONCLUSION: The patients who underwent
      arthroscopic tenotomy on the long head of the biceps with or without apparent
      clinical deformity from distal migration presented similar elbow flexion muscle
      strength.

PMID- 27047872
TI  - BIOMECHANICAL ACCESS METHOD FOR ANALYZING ISOMETRICITY IN RECONSTRUCTING THE
      MEDIAL PATELLOFEMORAL LIGAMENT.
AB  - OBJECTIVE: To present a biomechanical device for evaluating medial patellofemoral
      ligament (MPFL) reconstruction and its isometricity. METHODS: An accessible
      biomechanical method that allowed application of physiological and non
      physiological forces to the knee using a mechanical arm and application of
      weights and counterweights was developed, so as to enable many different
      evaluations and have a very accurate measurement system for distances between
      different structures, for analysis on experiments. This article describes the
      assembly of this system, and suggests some practical applications. Six cadaver
      knees were studied. The knees were prepared in a testing machine developed at the
      Biomechanics Laboratory of IOT-HCFMUSP, which allowed dynamic evaluation of
      patellar behavior, with quantification of patellar lateralization between 0
      degrees  and 120 degrees . The differences between the distances found with and
      without load applied to the patella were grouped according to the graft fixation
      angle (0 degrees , 30 degrees , 60 degrees  or 90 degrees ) and knee position
      (intact, damaged or reconstructed). RESULTS: There was a tendency for smaller
      lateral displacement to occur at fixation angles greater than 30 degrees of
      flexion, especially between the angles of 45 degrees  and 60 degrees  degrees of
      flexion, after the reconstruction. For the other angles, there was no statistical
      significance. CONCLUSION: The method developed is a useful tool for studies on
      the patellofemoral joint and the MPFL, and has a very accurate measurement system
      for distances between different structures. It can be used in institutions with
      fewer resources available.

PMID- 27047873
TI  - RISKS AND CONSEQUENCES OF USING THE TRANSPORTAL TECHNIQUE IN RECONSTRUCTING THE
      ANTERIOR CRUCIATE LIGAMENT: RELATIONSHIPS BETWEEN THE FEMORAL TUNNEL, LATERAL
      SUPERIOR GENICULAR ARTERY AND LATERAL EPICONDYLE OF THE FEMORAL CONDYLE.
AB  - OBJECTIVE: Define a security zone to avoid possibles vascular and ligamentar
      complications during anterior cruciate ligament reconstruction. METHODS:
      Arthroscopic reconstruction using the transtibial and transportal technique in
      cadaver knees was performed followed by dissection and measurement of the
      distance between the femoral tunnel and the proximal attachment of the lateral
      collateral ligament and the femoral tunnel and the lateral superior genicular
      artery. RESULTS: The measure of the analysed distances show us an aproximation
      between the major branch of the lateral superior genicular artery and the femoral
      insertion of the colateral lateral ligament and the femoral tunnel during the
      transportal technique. CONCLUSION: We realize that the use of technical ship it
      to arthroscopic ACL reconstruction has a higher probability of injury to the
      lateral geniculate artery and insertion of the lateral collateral ligament,
      promoting post-surgical complications such as instability of the knee,
      osteonecrosis of the femoral condyle and ligamentizacao graft.

PMID- 27047874
TI  - TIBIOTARSAL COMPRESSION ARTHRODESIS USING A LATERAL LOCKING PLATE.
AB  - OBJECTIVES: Tibiotalar (TT) arthrodesis is still a very important option in the
      treatment of primary or post-traumatic arthritis of the ankle but persists the
      controversy regarding the optimal method for the fixation of the arthrodesis
      site. No matter the implant used, the goal is to obtain a solid, healthy, pain
      free fusion. The purpose of the current study is to present the preliminary
      results of a novel laterally based tibiotalar compression arthrodesis system
      using a locked plate. METHODS: Thirteen consecutive patients with tibiotalar
      arthritis were submitted to an arthrodesis using a new lateral plating system.
      The average age was 59.7 years (range 36~72); nine patients were male and four
      female. Using a cutting guide, the remaining articular surfaces of the tibia and
      talus were removed. A compression device was applied to avoid malalignment of the
      ankle and a precontoured lateral locking plate was used to achieve the joint
      fusion. RESULTS: Both the AOFAS ankle-hindfoot score and the VAS score improved
      with the surgery. All patients' ankles fused by 6 months. In all patients we
      found a very good alignment in the sagittal, coronal and transverse planes.
      CONCLUSION: We believe that a combination of a bilateral compression, contoured
      bony cuts, and lateral locked plating offers a novel, accurate and useful
      technique for ankle arthrodesis.

PMID- 27047875
TI  - MIDFOOT CHARCOT ARTHROPATHY IN DIABETIC PATIENTS: COMPLICATION OF AN EPIDEMIC
      DISEASE.
AB  - OBJECTIVES: To outline the epidemiological profile of diabetic patients with
      Charcot arthropathy affecting the midfoot alone or extending from the midfoot to
      the hindfoot; To assess the results from the treatment that these patients
      undergo, according to a preestablished protocol, over the medium term. METHODS:
      We retrospectively evaluated 88 patients (110 extremities) with Charcot
      arthropathy of the midfoot. The minimum follow-up period was 12 months. We
      included 45 patients with Charcot arthropathy affecting the tarsal-metatarsal
      joints (51%); 20 patients in whom the talonavicular, calcaneocuboid and subtalar
      joints were affected (23%); and 23 patients in whom both the midfoot and hindfoot
      were affected (26%), as described by Brodsky and Trepman. We defined the
      treatment as successful when a functional foot was preserved; and unsuccessful
      when the foot was amputated. RESULTS: From treating Charcot arthropathy primarily
      involving the midfoot were satisfactory in the cases of 75 patients (85%) treated
      according to our protocol. For the patients with severe lesions affecting both
      the midfoot and the hindfoot, a greater number of complex operations (i.e.
      arthrodesis) were needed in order to obtain the same overall rate of satisfactory
      results. The osteoarticular lesions originating in the midfoot probably extended
      progressively to the hindfoot because of delayed diagnosis with inadequate early
      treatment. CONCLUSION: It was possible to preserve a functional extremity in 85%
      of the patients. Severe lesions involving the midfoot and extending to the
      hindfoot required a greater number of surgical procedures to treat them.

PMID- 27047876
TI  - AVASCULAR NECROSIS OF THE FEMORAL HEAD IN HIV-INFECTED PATIENTS: PRELIMINARY
      RESULTS FROM SURGICAL TREATMENT FOR CERAMIC-CERAMIC JOINT REPLACEMENT.
AB  - OBJECTIVES: To evaluate the initial functional results and early complication
      rate of ceramic-ceramic total hip replacements among patients living with HIV who
      presented osteonecrosis of the femoral head. METHOD: Twelve HIV-positive patients
      with a diagnosis of osteonecrosis of the incongruent femoral head were evaluated
      using clinical and laboratory criteria and the WOMAC functional scale before and
      after treatment with joint replacement. RESULTS: We observed that 83.3% of the
      subjects were taking protease inhibitors, 75% had dyslipidemia and 66.6% had
      lipodystrophy syndrome. The improvement over the evolution of the WOMAC score was
      statistically significant at six and twelve months after the operation, in
      comparison with the preoperative score. We did not observe complications
      secondary to this procedure. CONCLUSION: Total hip arthroplasty with a ceramic
      ceramic implant for treating avascular necrosis of the hip is an appropriate
      surgical option for this portion of the population. It provides a significant
      initial functional improvement and a low early complication rate.

PMID- 27047877
TI  - TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS.
AB  - OBJECTIVE: To study factors possibly associated with tumor contamination in the
      biopsy path of primary malignant bone tumors. METHOD: Thirty-five patients who
      underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and
      chondrosarcoma were studied retrospectively. The sample was analyzed to
      characterize the biopsy technique used, histological type of the tumor,
      neoadjuvant chemotherapy used, local recurrences and tumor contamination in the
      biopsy path. RESULTS: Among the 35 patients studied, four cases of contamination
      occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from
      chondrosarcoma. There was no association between the type of tumor and presence
      of tumor contamination in the biopsy path (p = 0.65). There was also no
      association between the presence of tumor contamination and the biopsy technique
      (p = 0.06). On the other hand, there were associations between the presence of
      tumor contamination and local recurrence (p = 0.01) and between tumor
      contamination and absence of neoadjuvant chemotherapy (p = 0.02). CONCLUSION:
      Tumor contamination in the biopsy path of primary malignant bone tumors was
      associated with local recurrence. On the other hand, the histological type of the
      tumor and the type of biopsy did not have an influence on tumor contamination.
      Neoadjuvant chemotherapy had a protective effect against this complication.
      Despite these findings, tumor contamination is a complication that should always
      be taken into consideration, and removal of the biopsy path is recommended in
      tumor resection surgery.

PMID- 27047879
TI  - RELATIONSHIP BETWEEN RIGIDITY OF EXTERNAL FIXATOR AND NUMBER OF PINS: COMPUTER
      ANALYSIS USING FINITE ELEMENTS.
AB  - OBJECTIVE: To analyze the rigidity of a platform-type external fixator assembly,
      according to different numbers of pins on each clamp. METHODS: Computer
      simulation on a large-sized Cromus dynamic external fixator (Baumer SA) was
      performed using a finite element method, in accordance with the standard ASTM
      F1541. The models were generated with approximately 450,000 quadratic tetrahedral
      elements. Assemblies with two, three and four Schanz pins of 5.5 mm in diameter
      in each clamp were compared. Every model was subjected to a maximum force of 200
      N, divided into 10 sub-steps. For the components, the behavior of the material
      was assumed to be linear, elastic, isotropic and homogeneous. For each model, the
      rigidity of the assembly and the Von Mises stress distribution were evaluated.
      RESULTS: The rigidity of the system was 307.6 N/mm for two pins, 369.0 N/mm for
      three and 437.9 N/mm for four. CONCLUSION: The results showed that four Schanz
      pins in each clamp promoted rigidity that was 19% greater than in the
      configuration with three pins and 42% greater than with two pins. Higher tension
      occurred in configurations with fewer pins. In the models analyzed, the maximum
      tension occurred on the surface of the pin, close to the fixation area.

PMID- 27047878
TI  - THE EFFECT OF 2-BUTYL-CYANOACRYLATE ADHESIVE IN OSTEOTOMIES AND BONE GRAFTS IN
      RABBITS: MACROSCOPIC AND RADIOGRAPHIC CHARACTERISTICS.
AB  - OBJECTIVE: To evaluate the effect of butyl-2-cyanoacrylate tissue adhesive in
      osteotomies and bone grafts, with regard to macroscopic and radiographic
      characteristics. METHODS: Forty-eight rabbits were used, randomly divided into
      four groups of 12 animals, with observation periods of two, four, eight and 16
      weeks. Both thoracic limbs were operated in each animal and two osteotomies were
      performed in each of the radii, withdrawing a bone fragment (bone graft) of 1 cm
      in length. On one side, the bone graft was then replaced and a drop of adhesive
      was applied to each of the osteotomies. On the other side, the same procedure was
      performed without applying the adhesive. The rejection level for the nullity
      hypothesis was set at 0.05% or 5%. RESULTS: Blue marks were present in all the
      surgical specimens in which adhesive was applied. From the fourth week onwards,
      there was absence of movement of the bone grafts with adhesive and control. In
      group A, in the proximal osteotomies with adhesive, there was less deviation of
      the bone graft (p = 0.02). In group C, the union (p = 0.03) and the integration
      of the bone graft (p = 0.02) were better in the proximal osteotomies with
      adhesive. CONCLUSIONS: The adhesive was not completely metabolized within 16
      weeks. There was clinical consolidation of the osteotomies within four weeks. The
      adhesive stabilized the bone graft within the first weeks and did not interfere
      with the consolidation of the osteotomies, or the integration of the bone graft
      in radiographic observations.

PMID- 27047880
TI  - IMPORTANCE OF A NATIONAL ARTHROPLASTY REGISTER FOR IDENTIFICATION BY MEDICAL
      EXAMINER.
AB  - Mass catastrophes are realities that come to pass with lamentable frequency. In
      such situations, one of the fundamental forensic problems is in relation to
      identifying the victims. All the elements that might be capable of contributing
      towards this identification process are essential, and among these are orthopedic
      prostheses, which frequently remain intact. These prostheses consist basically of
      polymers, ceramics or metals. Metal components, which are usually composed of
      titanium, chromium, cobalt or steel alloys, are resistant to violent trauma or
      high temperatures. Human identification is possible if the identity of the
      implant is established and if this can be correlated with the individual in whom
      it was implanted. The logo on the prosthesis establishes who the manufacturer was
      and the serial number can be compared with the clinical process or with a
      prosthesis register, as has been implemented in several countries. The
      information in the database should include the patient's name, the implant model
      and its serial number, for consultation only in cases of forensic identification,
      while obviously respecting ethical issues of privacy. This article highlights the
      importance of creating a national prosthesis register. 

PMID- 27047881
TI  - OSTEOID OSTEOMA IN SCAPHOID: CASE REPORT.
AB  - Osteoid osteoma is a benign osteoblastic tumor that is unusual in the hand. A
      location in the carpal bones is infrequent, which leads to errors in diagnosing
      it because of polymorphism of the clinical symptoms. Reviewing the literature
      shows that nine cases of osteoid osteoma in the scaphoid have been reported.
      Here, one case of osteoid osteoma in the scaphoid that was initially treated as
      De Quervain's stenosing tenosynovitis is reported, with a definitive diagnosis
      that was delayed for five years. 

PMID- 27047882
TI  - SIMULTANEOUS BILATERAL TEAR OF THE KNEE EXTENSOR MECHANISM IN A PRE-ADOLESCENT:
      CASE REPORT.
AB  - Unilateral tearing of a patellar tendon and a contralateral sleeve fracture in a
      pre-adolescent are rare lesions. We report a case in which a pre-adolescent
      sustained a fall while jumping during a soccer match. No predisposing risk
      factors were identified. The injuries were treated with surgical repairs and
      transosseous suturing. The aim of this study was to present a case of spontaneous
      concurrent tearing of the extensor mechanism of the knee in a pre-adolescent. 

PMID- 27047883
TI  - PROXIMAL FEMORAL EPIPHYSIOLYSIS AND SUBCLINICAL HYPOTHYROIDISM: CASE REPORT.
AB  - Proximal femoral epiphysiolysis is an orthopedic disease that is prevalent during
      adolescence, because this coincides with the time of greatest growth of
      osteomuscular structures. Curiously, some patients present this disease early,
      and this outcome converts to the possible etiological explanation that the
      slippage might occur through a growth spurt. For these patients, the genesis of
      the slippage has not yet been elucidated, but endocrine disorders have been noted
      as possible causes. In an attempt to strengthen the theory of endocrinological
      etiology and present the results from surgical treatment for this pathological
      condition, the case of a male patient aged 9 years and 3 months with proximal
      femoral epiphysiolysis and subclinical hypothyroidism who was diagnosed and
      treated at our university's teaching hospital is reported here. 

PMID- 27047884
TI  - A hundred years of knee arthroscopy.

PMID- 27047885
TI  - PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN ORTHOPAEDIC SURGERY.
AB  - The relevance of prophylaxis of venous thromboembolism and its complications in
      orthopedic surgery is increasingly significant. This review discusses the
      pathophysiology of thrombus formation in general and orthopedic surgery, its
      incidence, predisposing factors and complications. It also presents an updated
      presentation and critique of prophylaxis currently available in our environment. 

PMID- 27047886
TI  - COMPARISON OF VOLUMES OCCUPIED BY DIFFERENT INTERNAL FIXATION DEVICES FOR FEMORAL
      NECK FRACTURES.
AB  - OBJECTIVE: The objective of this paper is to measure the volume occupied by the
      most widely used internal fixation devices for treating femoral neck fractures,
      using the first 30, 40 and 50 mm of insertion of each screw as an approximation.
      The study aimed to observe which of these implants caused least bone aggression.
      METHODS: Five types of cannulated screws and four types of dynamic hip screws
      (DHS) available on the Brazilian market were evaluated in terms of volume
      differences through water displacement. RESULTS: Fixation with two cannulated
      screws presented significantly less volume than shown by DHS, for insertions of
      30, 40 and 50 mm (p=0.01, 0.012 and 0.013, respectively), fixation with three
      screws did not show any statistically significant difference (p= 0.123, 0.08 and
      0.381, respectively) and fixation with four cannulated screws presented larger
      volumes than shown by DHS (p=0.072, 0.161 and 0.033). CONCLUSIONS: Fixation of
      the femoral neck with two cannulated screws occupied less volume than DHS, with a
      statistically significant difference. The majority of screw combinations did not
      reach statistical significance, although fixation with four cannulated screws
      presented larger volumes on average than those occupied by DHS.

PMID- 27047887
TI  - SUPRACONDYLAR FRACTURE OF THE HUMERUS IN CHILDREN: FIXATION WITH TWO CROSSED
      KIRSCHNER WIRES.
AB  - OBJECTIVE: To analyze and present the surgical results from unstable
      supracondylar fractures of the humerus in children, treated by means of reduction
      and percutaneous fixation using two crossed Kirschner wires. METHODS: A cross
      sectional study was conducted on 20 children, taking into consideration sex, age
      at the time of the fracture, age at the time of the assessment, side affected,
      type and mechanism of trauma, postoperative complications and radiographic and
      clinic variables. RESULTS: Ten fractures were observed in the left arm and ten in
      the right arm. The age at the time of the fracture ranged from 2 to 13 years
      (mean: 5.9 +/- 2.48 years). Three fractures were classified as type II and 17 as
      type III. The length of follow-up ranged from four months to three years.
      Baumann's angle ranged from 69 to 100 (mean: 78.3) and cubitus varus was observed
      in four patients (values ranging from 84 to 100). According to the modified
      Flynn's criteria, 20 cases presented satisfactory outcomes: 17 excellent (85%),
      two good (10%) and one regular (5%). Two patients presented limited range of
      motion, two had paresthesia in the cubital region and one had transient
      neuropraxia of the ulnar nerve for six weeks. CONCLUSION: Percutaneous fixation
      with two crossed Kirschner wires leads to good results when carried out under
      direct viewing and with isolation of the ulnar nerve.

PMID- 27047888
TI  - IINCIDENCE OF ANKLE SPRAINS IN SOCCER PLAYERS WITH JOINT HYPERMOBILITY SYNDROME.
AB  - OBJECTIVE: Eighty-three soccer players aged between 14 and 19 years, in the basic
      category of a professional soccer club in the city of Belo Horizonte, were
      followed up during the 2009 season. METHODS: A prospective observational cohort
      study was conducted, in which these soccer players were divided randomly into two
      groups. The first consisted of individuals with joint hypermobility syndrome
      (JHS), totaling 22 players, and the second was a control group with 61 players
      without this syndrome, determined through a physical examinati. RESULTS: Both
      groups were studied with regard to incidence of ankle sprains. At the end of this
      period, the data were compiled and statistical analysis was performed. A total of
      43 cases of ankle injury due to sprains were recorded, of which nine episodes
      were in players with JHS, thus making p = 0.106. The significance level was 5%.
      CONCLUSION: We were able to conclude that in our study there was insufficient
      evidence to assert that there is an association with increased incidence of ankle
      sprains among patients with JHS.

PMID- 27047889
TI  - VALUE OF PREOPERATIVE RADIOGRAPHIC EVALUATIONS ON KNEE BONE DEFECTS FOR REVISION
      ARTHROPLASTY.
AB  - OBJECTIVE: To evaluate the value of preoperative radiographic evaluations for
      total knee arthroplasty (TKA) revision. METHODS: Thirty-one knees that were
      operated between 2006 and 2008, in a consecutive series of cases of TKA revision
      surgery were analyzed retrospectively. The following criteria were evaluated:
      number of wedges or structured bone grafts used for filling the bone defects;
      locations of the wedges and bone grafts used; and mean thickness of the
      polyethylene used. The AORI classification was previously established based on
      preoperative radiographs, using preestablished criteria. After the analysis, the
      knees were divided into four groups (I, IIA, IIB and III). RESULTS: The mean
      number of wedges or grafts used in each knee progressively increased among the
      groups (group I: 1.33; group IIA: 2; group IIB: 4.33; and group III: 4.83) (P =
      0.0012). The commonest locations were medial in the tibia and posteromedial in
      the femur. There were no statistically significant differences in the thickness
      of the polyethylene used. CONCLUSION: The AORI classification for bone defects in
      the knee, based on preoperative radiographs, showed a correlation with increasing
      need to use wedges and/or structured grafts in TKA revisions. However, up to 46%
      of the knees in groups I and IIA presented bone defects of up to 5 mm that were
      not diagnosed by means of preoperative radiographs.

PMID- 27047890
TI  - EPIDEMIOLOGICAL STUDY ON TENDON RUPTURES OF THE KNEE EXTENSOR MECHANISM AT A
      LEVEL 1 HOSPITAL.
AB  - OBJECTIVES: The purpose of the present study was to review the epidemiological
      aspects of tendon ruptures of the knee extensor apparatus at a level 1 hospital.
      METHODS: We retrospectively analyzed 76 lesions of the knee extensor apparatus
      that were treated surgically at the Miguel Couto Municipal Hospital between March
      2004 and March 2011. We took into consideration age, sex, trauma mechanism,
      anatomical classification of the lesion, affected side, comorbidities and
      associated lesions. RESULTS: Among the patients studied, 68 were male and the
      mean age was 36 years. Regarding the trauma mechanism, 62 lesions occurred due to
      direct trauma; the right side was affected in 21 cases; eight presented
      comorbidities and four presented associated lesions. CONCLUSION: The majority of
      the patients were male, at an economically active age (young people), and were
      victims of direct trauma. Ruptures of the patellar ligament were the most
      frequent lesions. Associated lesions were rare and comorbidities were infrequent
      in our sample.

PMID- 27047891
TI  - UNICOMPARTMENTAL KNEE ARTHROPLASTY: CURRENT PERSPECTIVES AND TRENDS IN BRAZIL.
AB  - OBJECTIVE: The aim of this study was to evaluate the approaches and procedures
      used by Brazilian orthopedic surgeons for treating osteoarthrosis by means of
      unicompartmental knee arthroplasty and high tibial osteotomy of the knee.
      METHODS: A questionnaire with 14 closed questions was developed and applied to
      Brazilian knee surgeons during the three days of the 43(rd) Brazilian Congress of
      Orthopedics and Traumatology. RESULTS: A total of 113 surgeons filled out the
      questionnaire completely and became part of the sample analyzed. In this study,
      the majority of the surgeons performed fewer than five unicompartmental knee
      arthroplasty procedures/year (61.1%) and between 5 and 15 high tibial osteotomy
      procedures/year (37.2%). Use of computerized navigation systems during surgery
      remains uncommon in our environment, since only 0.9% of the specialists were
      using it. 65.5% of the surgeons reported that they had chosen to use total knee
      arthroplasty rather than partial arthroplasty due to lack of familiarity with the
      surgical technique. When asked about the possibility that the number of
      unicompartmental prostheses used in Brazil would grow as surgeons in this country
      become increasingly familiar with the technique, 80.5% of the respondents
      believed in this hypothesis. In this sample, we found that the greater the
      surgeon's experience was, the greater the numbers of unicompartmental prostheses
      and tibial osteotomies performed annually were (r = 0.550 and r = 0.465,
      respectively; p < 0.05). CONCLUSIONS: There is a clear evolutional trend towards
      treatment of unicompartmental osteoarthritis using partial knee arthroplasty in
      Brazil. However, further prospective controlled studies are needed in order to
      evaluate the clinical and scientific benefits of these trends.

PMID- 27047892
TI  - ASSOCIATION CLINICAL-RADIOGRAPHIC OF THE ACROMION INDEX AND THE LATERAL ACROMION
      ANGLE.
AB  - OBJECTIVE: To evaluate the clinical-radiographic subacromial disease symptoms
      correlated with adaptation of the measure of lateral acromion angle and its
      respective measuring radiographic acromial index. METHODS: In the period between
      october 2010 and february 2011 were evaluated 55 painful shoulders with Neer test
      and true anteroposterior radiography. Patients were divided into two groups, with
      Neer test positive and negative. The index measuring the acromion and the lateral
      acromion angle have been standardized, and compared using statistical averages of
      0.7 and 75 degrees , respectively. RESULTS: The predominant symptom in the
      population, females (72.73%), age less than 59 years (62.5%) and dominant side
      (65.31%). The acromion index above 0.7 was found to be symptomatic in 66.67% and
      lateral acromion angle less than 75  degrees  in 82.61%. When associated methods,
      62.5% had positive clinical (p<0.083). CONCLUSION: The determination of
      radiographic acromial index and the lateral acromion angle together seem to be
      statistically associated with the disease of subacromial impingement.

PMID- 27047893
TI  - TENOTOMY WITH OR WITHOUT TENODESIS OF THE LONG HEAD OF THE BICEPS USING REPAIR OF
      THE ROTATOR CUFF.
AB  - OBJECTIVE: To compare the functional results among patients undergoing tenotomy
      with or without tenodesis of the long head of the biceps associated with
      arthroscopic repair of rotator cuff injuries, with a minimum two-year follow-up.
      METHOD: This was a retrospective non-randomized trial with evidence level III, in
      which the medical files of 77 patients with lesions of the long head of the
      biceps were reviewed and clinically reassessed. Among these, 55 patients
      underwent tenotomy without tenodesis and 22 underwent tenotomy with tenodesis,
      with outpatient follow-up for at least two years. The age, dominant side,
      operated side, lesion size using the Gartsman classification, pre and
      postoperative range of motion, presence or absence of the Popeye sign, pain in
      the bicipital groove and assessments using the University of California at Los
      Angeles (UCLA) score and the elbow strength index. RESULTS: The mean UCLA score
      of the sample went from 16.92 (range: 8 to 25) to 31.45 (range: 13 to 35) (p <
      0.001). Comparison of the pre and postoperative UCLA scores in the two groups
      showed that the difference in the group with tenotomy and tenodesis was 15.95 and
      in the group with tenotomy alone, 14.62 (p = 0.023). However, there was no
      statistical significance in comparing the groups regarding pain in the bicipital
      groove, Popeye sign or elbow strength index. CONCLUSION: This study showed that
      the difference in UCLA scores was statistically significant. The group with
      tenotomy and tenodesis of the long head of the biceps presented better functional
      results.

PMID- 27047895
TI  - SUBCUTANEOUS ANTERIOR TRANSPOSITION FOR TREATMENT OF CUBITAL TUNNEL SYNDROME: IS
      THIS METHOD SAFE AND EFFECTIVE?
AB  - OBJECTIVE: To evaluate the results from subcutaneous anterior transposition of
      the cubital nerve for treating cubital tunnel syndrome (CTS) and the influence of
      prognostic factors such as preoperative McGowan stage, age and duration of
      symptoms. METHODS: 36 patients with CTS who underwent subcutaneous anterior
      transposition of the cubital nerve between 2006 and 2009 were evaluated after an
      average follow-up of 28 months. Their mean age was 41.6 years. Nine patients were
      in McGowan stage I, 18 in stage II and nine in stage III. RESULTS: There was a
      statistically significant improvement in sensory and motor deficits. 78% of the
      patients with severe neuropathy improved after surgery. According to the modified
      Bishop score, 21 patients (58.3%) had excellent results, seven (19.4%) good, six
      (16.7%) satisfactory and two (5.55%) poor. The satisfaction rate was 86% and 72%
      of the patients recovered their daily activities without limitations. CONCLUSION:
      The severity of neuropathy and preoperative duration of symptoms, but not age,
      had a negative influence on the outcome. The subcutaneous anterior transposition
      of the cubital nerve is safe and effective for treating CTS of different degrees
      of severity. Given the major prognostic factors identified, surgical treatment
      should be advised as soon as axonal loss has become clinically evident.

PMID- 27047894
TI  - PLATELET-RICH PLASMA IN ARTHROSCOPIC REPAIRS OF COMPLETE TEARS OF THE ROTATOR
      CUFF.
AB  - OBJECTIVE: To evaluate shoulder functional results and the retear rate of
      arthroscopic repair of the rotator cuff augmented with platelet-rich plasma
      (PRP). METHODS: Prospective case series with single-row arthroscopic repair of
      the rotator cuff augmented with PRP. Only cases of isolated supraspinatus tears
      with retraction of less than 3 cm were included in this series. The PRP used was
      obtained by apheresis. It was applied on liquid consistency in its activated
      form, with the addition of autologous thrombin. Patients were evaluated after 12
      months of the surgical procedure. The Constant-Murley, UCLA and VAS scales were
      used, and the retear rate was assessed using magnetic resonance imaging (MRI).
      RESULTS: Fourteen patients were evaluated (14 shoulders). The mean Constant
      Murley score was 45.64 +/- 12.29 before the operation and evolved to 80.78 +/-
      13.22 after the operation (p < 0.001). The UCLA score increased from 13.78 +/-
      5.66 to 31.43 +/- 3.9 (p < 0.001). The patients' pain level decreased from a
      median of 7.5 (p25% = 6, p75% = 8) to 0.5 (p25% = 0, p75% = 3) (p = 0.0013)
      according to the VAS score. None of the patients presented complete retear. Three
      patients (21.4%) showed partial retear, without transfixation. Only one patient
      developed complications (adhesive capsulitis). CONCLUSION: Patients submitted to
      arthroscopic rotator cuff repair augmented with PRP showed significant functional
      improvement and none of them had complete retearing.

PMID- 27047896
TI  - CIRCUMFERENTIAL PROXIMAL FEMORAL ALLOGRAFTS IN TOTAL HIP ARTHROPLASTY REVISION
      SURGERY.
AB  - OBJECTIVE: To evaluate the clinical and radiographic results from patients who
      underwent femoral reconstruction secondary to loosening of total hip
      arthroplasty, using circumferential proximal femoral allografts and cemented
      implants. METHODS: A retrospective study was conducted on 32 patients (33 hips)
      who underwent femoral reconstruction secondary to loosening of total hip
      arthroplasty, using circumferential proximal femoral allografts and cemented
      implants. Among these patients, 28 (29 hips) fulfilled all the requirements for
      this study. The mean follow-up was five years and two months. The clinical
      evaluation was done in accordance with the Harris Hip Score. Radiographically,
      the patients were assessed regarding reabsorption and consolidation of the
      allograft, migration of the greater trochanter, stability of the femoral
      component and heterotypic calcification. RESULTS: The average preoperative Harris
      Hip Score was 32 points. At the last postoperative follow-up, the average score
      was 82 points. Allograft resorption of some degree was seen in nine hips (31%).
      Regarding consolidation, 24 cases (82.8%) showed full consolidation, three
      (10.3%) showed partial consolidation and two (6.9%) showed pseudarthrosis. All
      femoral components were stable. According to the criteria established, 27 cases
      (93.1%) were considered to be successful reconstructions after a mean follow-up
      of five years and two months. CONCLUSION: From the results obtained, it was
      concluded that use of circumferential proximal femoral allografts in selected
      cases of femoral reconstruction secondary to loosening of arthroplasty presented
      a high survival rate from the reconstruction over an average follow-up of five
      years and two months.

PMID- 27047897
TI  - ANTEROGRADE PERCUTANEOUS TREATMENT OF LESSER METATARSAL FRACTURES: TECHNICAL
      DESCRIPTION AND CLINICAL RESULTS.
AB  - OBJECTIVE: The aim of this study was to evaluate the results obtained using the
      anterograde percutaneous fixation technique for treating shaft and neck fractures
      of the lesser metatarsals. METHODS: We prospectively evaluated 14 patients
      between 2003 and 2008, taking into consideration the topography of the fracture,
      trauma mechanism, associated comorbidities and AOFAS score for the forefoot.
      RESULTS: The anatomical region most affected was the metatarsal neck (79%).
      Involvement of multiple metatarsals (53%) was more common than isolated fractures
      (47%). Low-energy trauma (79%) was more frequent than high-energy trauma (21%).
      Female patients with diabetes had the worst postoperative functional results.
      There were no postoperative complications relating to the type of treatment
      instituted. CONCLUSION: The surgical technique presented was efficient for
      treating fractures of the lesser metatarsals, with a lower complication rate than
      shown by other established techniques in the literature.

PMID- 27047898
TI  - PLANTAR THROMBOPHLEBITIS: MAGNETIC RESONANCE IMAGING FINDINGS.
AB  - OBJECTIVE: Demonstrate the magnetic resonance imaging (MRI) findings in plantar
      thrombophlebitis. METHODS: Retrospective review of twenty patients with pain in
      the plantar region of the foot, in which the MRI findings indicated plantar
      thrombophlebitis. RESULTS: A total of fourteen men and six women, mean age 46.7
      years were evaluated. Eight of these patients also underwent Doppler
      ultrasonography, which confirmed the thrombophlebitis. The magnetic resonance
      images were evaluated in consensus by two radiologists with experience in
      musculoskeletal radiology (more than 10 years each), showing perivascular edema
      in all twenty patients (100%) and muscle edema in nineteen of the twenty patients
      (95%). All twenty patients had intraluminal intermediate signal intensity on T2
      weighted (100%) and venous ectasia was present in seventeen of the twenty cases
      (85%). Collateral veins were visualized in one of the twenty patients (5%). All
      fourteen cases (100%), in which intravenous contrast was administered, showed
      perivenular tissues enhancement and intraluminal filling defect. Venous ectasia,
      loss of compressibility and no flow on Doppler ultrasound were also observed in
      all eight cases examined by the method. CONCLUSION: MRI is a sensitive in the
      evaluation of plant thrombophlebitis in patients with plantar foot pain.

PMID- 27047899
TI  - BOVINE LYOPHILIZED GRAFT (BLG): HISTOLOGICAL ANALYSIS ON BEHAVIOR IN HUMANS AFTER
      49 MONTHS.
AB  - OBJECTIVE: To analyze the histological behavior of bovine lyophilized grafts
      (BLG) produced according to a protocol developed by the first author, in humans
      over a 49-month period by measuring the graft/bone neoformation ratio in relation
      to the total mineralized area. METHODS: This was a case series involving 12
      patients: eight females (66%) and four males (34%), totaling 13 biopsies. BLG was
      used, and surgical reintervention was subsequently required during the period
      2000 to 2011. The slides produced were stained with hematoxylin-eosin (HE), were
      analyzed by a pathologist and were digitized for the proposed evaluation.
      RESULTS: The mean age was 57 years and the mean follow-up was 49 months (range: 6
      115). The average proportion of BLG was 42% (range: 13-85) and neoformed bone,
      58% (range: 15-87) in relation to the total area mineralized. CONCLUSIONS: This
      study demonstrated that the BLG used presented osteoconductive characteristics
      and biocompatibility. BLG is a therapeutic option that can be used in orthopedic
      surgery in which bone defects need to be filled.

PMID- 27047900
TI  - INTERNAL HEMIPELVECTOMY: REPORT ONEIGHT CASES.
AB  - Internal hemipelvectomy is a surgical procedure adequate for treatment of certain
      tumors of the pelvic girdle. Being a lower limb-preserving approach, it is a
      therapeutic alternative to the classical interilioabdominal amputation and hip
      joint disarticulation. According to Enneking's classification, there are four
      types of internal hemipelvectomies, although the association of different types
      of resection in the same procedure is feasible if necesary. This surgical
      approach should be correctly indicated to positively affect the patient's
      morbidity, mortality and quality of life. We report eight cases of internal
      hemipelvectomy in patients diagnosed with tumors of the pelvic girdle. We also
      discuss the neoadjuvant and adjuvant treatments used, along with their follow-up.

PMID- 27047901
TI  - ISCHIOFEMORAL IMPINGEMENT - AN ETIOLOGY OF HIP PAIN: CASE REPORT.
AB  - An association between hip pain and quadratus femoris muscle abnormality on
      magnetic resonance imaging (MRI) with concurrent narrowing of the ischiofemoral
      space has been reported in the recent literature. This raises the possibility
      that the muscle damage observed is due to ischiofemoral impingement. This
      diagnosis has been noted in middle-aged females either with or without a history
      of trauma or surgery, is a rarely described feature. We report here on a 31-year
      old woman who presented with non-traumatic hip pain and evidence of narrowing of
      the ischiofemoral space and edema in the quadratus femoris. Nonsurgical treatment
      was administered, which relieved her hip pain. The diagnosis of ischiofemoral
      impingement should be considered in female patients complaining of hip pain
      without any other evident cause. 

PMID- 27047902
TI  - LATERAL PAIN IN AN ATHLETE'S KNEE: A RARE CASE OF DISLOCATION OF THE FEMORAL
      BICEPS TENDON.
AB  - Dislocation of the femoral biceps tendon is rare and is described clinically in
      the literature as a lateral pain in the knee. It was initially reported as an
      anomalous insertion of the long head of the femoral biceps. Subsequently, it was
      found to be caused by abnormal mobility of the tendon over the prominence of the
      fibular head at certain angles of knee flexion. The objective of the present
      report was to describe and discuss a condition of lateral knee pain in a swimmer
      who started to present subluxation of the femoral biceps during sports practice,
      which incapacitated him from taking part in trials and competitions. The case is
      discussed in the light of the literature surveyed; the likelihood that the
      etiology for the trauma leading to this condition was repetition; and the
      surgical treatment instituted, which led to excellent results and the patient's
      return to his habitual sports practice. 

PMID- 27047903
TI  - TRANSLATION TO PORTUGUESE LANGUAGE AND CROSS-CULTURAL ADAPTATION OF THE MODIFIED
      ROWE SCORE FOR OVERHEAD ATHLETES.
AB  - Objetctive: Study was to translate and culturally adapt the modified Rowe score
      for overhead athletes. METHODS: The translation and cultural adaptation process
      initially involved the stages of translation, synthesis, back-translation, and
      revision by the Translation Group. It was than created the pre-final version of
      the questionnaire, being the areas "function" and "pain" applied to 20 athletes
      that perform overhead movements and that suffered SLAP lesions in the dominant
      shoulder and the areas "active compression test and anterior apprehension test"
      and "motion" were applied to 15 health professionals. RESULTS: During the
      translation process there were made little modifications in the questionnaire in
      order to adapt it to Brazilian culture, without changing the semantics and the
      idiomatic concept originally described. CONCLUSION: The questionnaire was easily
      understood by the subjects of the study, being possible to obtain the Brazilian
      version of the modified Rowe score for overhead athletes that underwent surgical
      treatment of the SLAP lesion.

PMID- 27047904
TI  - Pediatric Acute Respiratory Distress Syndrome: Fluid Management in the PICU.
AB  - The administration of an appropriate volume of intravenous fluids, while avoiding
      fluid overload, is a major challenge in the pediatric intensive care unit.
      Despite our efforts, fluid overload is a very common clinical observation in
      critically ill children, in particular in those with pediatric acute respiratory
      distress syndrome (PARDS). Patients with ARDS have widespread damage of the
      alveolar-capillary barrier, potentially making them vulnerable to fluid overload
      with the development of pulmonary edema leading to prolonged course of disease.
      Indeed, studies in adults with ARDS have shown that an increased cumulative fluid
      balance is associated with adverse outcome. However, age-related differences in
      the development and consequences of fluid overload in ARDS may exist due to
      disparities in immunologic response and body water distribution. This systematic
      review summarizes the current literature on fluid imbalance and management in
      PARDS, with special emphasis on potential differences with adult patients. It
      discusses the adverse effects associated with fluid overload and the
      corresponding possible pathophysiological mechanisms of its development. Our
      intent is to provide an incentive to develop age-specific fluid management
      protocols to improve PARDS outcomes. 

PMID- 27047905
TI  - Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug
      Therapies.
AB  - Limited research exists regarding the most aggressive forms of hepatoblastoma.
      Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not
      only difficult to attain but also challenging to characterize histologically. A
      community-driven approach to educating parents and families, regarding the need
      for donated tissue, is necessary for scientists to have access to resources for
      murine models and drug discovery. Herein, we describe the currently available
      resources, existing gaps in research, and the path to move forward for uniform
      cure of hepatoblastoma. 

PMID- 27047906
TI  - Mortality and Major Morbidity of Very-Low-Birth-Weight Infants in Germany 2008
      2012: A Report Based on Administrative Data.
AB  - BACKGROUND: Expectant parents of very preterm infants, physicians, and policy
      makers require estimates for chances of survival and survival without morbidity.
      Such estimates should derive from a large, reliable, and contemporary data base
      of easily available items known at birth. OBJECTIVE: To determine short-term
      outcome and risk factors in very-low-birth-weight preterm infants based on
      administrative data. METHODS: Anonymized routine data sets transmitted from
      hospital administrations to statutory health insurance companies were used to
      assess survival and survival free of major morbidities in a large cohort of
      preterm infants in Germany. RESULTS: After exclusion of infants with lethal
      malformations, there were 13,147 infants with a birth weight below 1,500 g
      admitted to neonatal care 2008-2012, of whom 1,432 infants (10.9%) died within
      180 days. Estimated 180 days survival probabilities were 0.632 (95% confidence
      interval 0.583-0.677) for infants with 250-499 g birth weight, 0.817 (0.799
      0.834) for 500-749 g, 0.931 (0.920-0.940) for 750-999 g, 0.973 (0.967-0.979) for
      1,000-1,249 g, and 0.985 (0.981-0.988) for 1,250-1,499 g. Estimated probabilities
      for survival without major morbidity (surgically treated intraventricular
      hemorrhage, necrotizing enterocolitis, intestinal perforation, or retinopathy)
      were 0.433 (0.384-0.481) for 250-499 g, 0.622 (0.600-0.643) for 500-749 g, 0.836
      (0.821-0.849) for 750-999 g, 0.938 (0.928-0.946) for 1,000-1,249 g, and 0.969
      (0.964-0.974) for 1,250-1,499 g, respectively. Prediction of survival and
      survival without major morbidities was moderately improved by adding sex, small
      for gestational age, and severe or moderate congenital malformation, increasing
      receiver operating characteristic areas under the curve from 0.839 (0.827-0.850)
      to 0.862 (0.852-0.874) (survival) and from 0.827 (0.822-0.842) to 0.852 (0.846
      0.863) (survival without major morbidities), respectively. CONCLUSION: The
      present analysis encourages attempts to use administrative data to investigate
      the association between risk factors and outcome in preterm infants.

PMID- 27047907
TI  - Are Children Like Werewolves? Full Moon and Its Association with Sleep and
      Activity Behaviors in an International Sample of Children.
AB  - In order to verify if the full moon is associated with sleep and activity
      behaviors, we used a 12-country study providing 33,710 24-h accelerometer
      recordings of sleep and activity. The present observational, cross-sectional
      study included 5812 children ages 9-11 years from study sites that represented
      all inhabited continents and wide ranges of human development (Australia, Brazil,
      Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, United
      Kingdom, and United States). Three moon phases were used in this analysis: full
      moon (+/-4 days; reference), half moon (+/-5-9 days), and new moon (+/-10-14
      days) from nearest full moon. Nocturnal sleep duration, moderate-to-vigorous
      physical activity (MVPA), light-intensity physical activity (LPA), and total
      sedentary time (SED) were monitored over seven consecutive days using a waist
      worn accelerometer worn 24 h a day. Only sleep duration was found to
      significantly differ between moon phases (~5 min/night shorter during full moon
      compared to new moon). Differences in MVPA, LPA, and SED between moon phases were
      negligible and non-significant (<2 min/day difference). There was no difference
      in the associations between study sites. In conclusion, sleep duration was 1%
      shorter at full moon compared to new moon, while activity behaviors were not
      significantly associated with the lunar cycle in this global sample of children.
      Whether this seemingly minimal difference is clinically meaningful is
      questionable. 

PMID- 27047908
TI  - Changing the Paradigm for the Treatment and Development of New Therapies for
      FSGS.
AB  - Focal segmental glomerulosclerosis (FSGS) is a renal pathology finding that
      represents a constellation of rare kidney diseases, which manifest as
      proteinuria, edema nephrotic syndrome, hypertension, and increased risk for
      kidney failure. Therapeutic options for FSGS are reviewed displaying the expected
      efficacy from 25 to 69% depending on specific therapy, patient characteristics,
      cost, and common side effects. This variability in treatment response is likely
      caused, in part, by the heterogeneity in the etiology and active molecular
      mechanisms of FSGS. Clinical trials in FSGS have been scant in number and slow to
      recruit, which may stem, in part, from reliance on classic clinical trial design
      paradigms. Traditional clinical trial designs based on the "learn and confirm"
      paradigm may not be appropriate for rare diseases, such as FSGS. Future drug
      development and testing will require novel approaches to trial designs that have
      the capacity to enrich study populations and adapt the trial in a planned way to
      gain efficiencies in trial completion timelines. A clinical trial simulation is
      provided that compares a classical and more modern design to determine the
      maximum tolerated dose in FSGS. 

PMID- 27047909
TI  - Mental and Emotional Health of Children Exposed to News Media of Threats and Acts
      of Terrorism: The Cumulative and Pervasive Effects.

PMID- 27047910
TI  - Commentary: Eysenck Personality Questionnaire Revised Psychoticism Predicts
      Motivational-Somatic Symptoms of Depression in Breast Cancer Survivors.

PMID- 27047911
TI  - Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes
      into the Environment in an Effort to Control Dengue.
AB  - BACKGROUND: In an effort to eliminate dengue, a successful technology was
      developed with the stable introduction of the obligate intracellular bacteria
      Wolbachia pipientis into the mosquito Aedes aegypti to reduce its ability to
      transmit dengue fever due to life shortening and inhibition of viral replication
      effects. An analysis of risk was required before considering release of the
      modified mosquito into the environment. METHODS: Expert knowledge and a risk
      assessment framework were used to identify risk associated with the release of
      the modified mosquito. Individual and group expert elicitation was performed to
      identify potential hazards. A Bayesian network (BN) was developed to capture the
      relationship between hazards and the likelihood of events occurring. Risk was
      calculated from the expert likelihood estimates populating the BN and the
      consequence estimates elicited from experts. RESULTS: The risk model for "Don't
      Achieve Release" provided an estimated 46% likelihood that the release would not
      occur by a nominated time but generated an overall risk rating of very low. The
      ability to obtain compliance had the greatest influence on the likelihood of
      release occurring. The risk model for "Cause More Harm" provided a 12.5%
      likelihood that more harm would result from the release, but the overall risk was
      considered negligible. The efficacy of mosquito management had the most
      influence, with the perception that the threat of dengue fever had been
      eliminated, resulting in less household mosquito control, and was scored as the
      highest ranked individual hazard (albeit low risk). CONCLUSIONS: The risk
      analysis was designed to incorporate the interacting complexity of hazards that
      may affect the release of the technology into the environment. The risk analysis
      was a small, but important, implementation phase in the success of this
      innovative research introducing a new technology to combat dengue transmission in
      the environment.

PMID- 27047912
TI  - Biosafety Initiatives in BMENA Region: Identification of Gaps and Advances.
AB  - INTRODUCTION: The objectives of this study were to identify and assess the impact
      of capacity-building biosafety initiatives and programs that have taken place in
      the broader Middle East and North Africa (BMENA) region between 2001 and 2013, to
      highlight gaps that require further development, and to suggest sustainable ways
      to build cooperative regional biosafety opportunities. METHODS: A cross-sectional
      study was conducted with two aspects (1) thorough desktop review of literature
      for all biosafety/biosecurity-related activities in the study countries, such as
      seminars, conferences, workshops, policy documents, technology transfer,
      sustained scientific endeavors between countries, etc. and (2) an online survey
      of scientists in countries in the region to get first-hand information about
      biosafety and biosecurity initiatives and gaps in their country. RESULTS: A total
      of 1832 initiatives of biosafety/biosecurity were recorded from 97 web links;
      70.68% (n = 1295) initiatives were focused on raising general awareness among the
      scientific community about biosafety/biosecurity/biocontainment. The most
      frequent areas of interest were biorisk management in biomedical and
      biotechnology laboratories 13% (n = 239), followed by living modified organisms
      (LMOs) 9.17% (n = 168). Hands-on training accounted for 2.67% (n = 49) of
      initiatives. Online survey results confirmed desktop review findings; however,
      the response rate was 11%.

PMID- 27047913
TI  - Federal Enactment of Healthy Homes Legislation in the United States to Improve
      Public Health.
AB  - Not all homes across America are "healthy" homes. This contributes to the poor
      health of Americans and exacerbates existing health conditions costing millions
      each year in health-care cost. Newer research is being conducted into strategies
      to alleviate biological, chemical, and physical hazards in the home, and various
      programs exist to assist the homeowner in making improvements in the quality of
      their home. Not every homeowner or renter nationwide or within community
      localities has access to these strategies or programs that could potentially
      improve their home environment and therefore the health of their family. The
      objective of this article is to propose elements of a policy to address this
      inconsistency and variation. This proposal centers around the federal enactment
      of a national policy demanding that each state implements a healthy homes program
      tailored to fit their specific state housing and health needs. Members of
      Congress from States that have successfully implemented healthy home programs
      should champion this policy. Organizations that recognize the impact of housing
      on health should support the development of a national healthy homes strategy.
      This article will discuss the need, outcomes, stakeholders, and minimum
      requirements of such a policy. 

PMID- 27047915
TI  - Editorial.

PMID- 27047914
TI  - Stressful Life Events and Risk of Depression 25 Years Later: Race and Gender
      Differences.
AB  - BACKGROUND: Although stressful life events (SLEs) predict subsequent risk of
      developing a major depressive episode (MDE), limited information exists on
      whether or not race and gender alters the predictive role of SLE on risk of MDE
      over a long-term period. The current study explored race and gender differences
      in the long-term predictive role of SLE at baseline (1986) on subsequent risk of
      MDE 25 years later (2011) in a nationally representative cohort in the United
      States. METHODS: Using a life course epidemiological approach, this longitudinal
      study borrowed data from the Americans' Changing Lives (ACL) Study 1986-2011.
      Main predictor of interest was baseline SLE over the last 3 years measured at
      1986. Main outcome was risk of MDE [Composite International Diagnostic Interview
      (CIDI)] 25 years later (2011). Covariates included demographics, socioeconomics,
      depressive symptoms [Center for Epidemiological Studies-Depression Scale (CES
      D)], chronic medical conditions, and health behaviors measured at baseline
      (1986). Gender and race were the focal moderators. We employed logistic
      regressions in the pooled sample, and specific to race and gender, to test
      whether or not SLE * race and SLE * gender interactions are significant. RESULTS:
      In the pooled sample, baseline SLE (1986) predicted risk of MDE 25 years later
      (2011). We also found a gender by SLE interaction, suggesting a stronger
      predictive role of SLE for subsequent clinical depression for men compared to
      women. Race did not modify the predictive role of SLE on subsequent risk of MDE
      25 years later. CONCLUSION: How SLE predicts MDE 25 years later differs for men
      and women, with a stronger predictive role for men compared to women. More
      research is needed to better understand the complex links between gender, sex,
      stress, and depression.

PMID- 27047916
TI  - Necrotizing Infundibular Crystalline Folliculitis: A Case Report of an
      Exceptional Lesion of Unknown Etiology.
AB  - Necrotizing infundibular crystalline folliculitis is a rare follicular lesion of
      which the etiology is not well understood. Here we describe the case of a 71-year
      old male patient presenting with multiple hyperkeratotic lesions localized on the
      forehead. Histopathological analysis of one of the lesions revealed a follicular
      invagination containing cellular debris and keratin lamellae containing
      filamentous mucinous material and numerous crystals birefringent in polarized
      light microscopy. 

PMID- 27047917
TI  - Cutaneous Angioneurofibroma: A New Histopathological Variant of Neurofibroma.
AB  - Cutaneous neurofibromas are benign dermal tumors composed of spindle cells in a
      myxoid stroma containing numerous blood vessels. Here we describe 6 cases of
      solitary cutaneous neurofibroma showing unusually higher density of blood vessels
      in the stroma when compared to that of classical neurofibromas. We propose this
      lesion to be a new histopathological variant of neurofibroma and name it
      angioneurofibroma. 

PMID- 27047919
TI  - Trauma-Induced Cutaneous Focal Mucinosis of the Mammary Areola: An Unusual
      Presentation.
AB  - Cutaneous focal mucinosis (CFM) is a localized form of cutaneous dermal mucinosis
      clinically presenting as an asymptomatic skin-colored papule or nodule. The
      etiopathogenesis of CFM is unclear, but it is thought to represent a reactive
      lesion. Although trauma has been suspected as a triggering factor, it has never
      been proven in cases of CFM. We report 2 male patients with trauma-induced CFM
      arising at the mammary areola, which is an unusual site for CFM. Both male
      patients presented with a solitary nodular lesion of up to 2 cm in diameter at
      the right areola. Histology was characterized by circumscribed abundant dermal
      mucin deposits in a polylobulated pattern without an increased number of
      fibroblasts or capillaries and with absence of an inflammatory infiltrate. Alcian
      blue stain at pH 2.5 highlighted the mucin deposits. Immunohistochemistry showed
      partial expression of FXIIIa by 30% of the stromal cells, but no reactivity for
      CD34, smooth muscle actin, desmin, CD68 and S-100. A history of trauma (laser
      based epilation, piercing) preceded the development of CFM in both patients.
      Surgical excision resulted in complete remission without recurrence. Follow-up in
      both our patients did not reveal recurrences. CFM has to be distinguished from
      benign and malignant myxoid neoplasms. 

PMID- 27047918
TI  - Whole Transcriptome Analysis (RNA Sequencing) of Peripheral Blood Mononuclear
      Cells of Vitiligo Patients.
AB  - Vitiligo is an idiopathic disorder characterized by depigmented patches on the
      skin due to a loss of melanocytes. The cause of melanocyte destruction is not
      fully understood. The aim of this study was to detect the potential pathways
      involved in the vitiligo pathogenesis to further understand the causes and entity
      of vitiligo. For that the transcriptome of peripheral blood mononuclear cells of
      4 vitiligo patients and 4 control subjects was analyzed using the SOLiD System
      platform and whole transcriptome RNA sequencing application. Altogether 2,470
      genes were expressed differently and GRID2IP showed the highest deviation in
      patients compared to controls. Using functional analysis, altogether 993
      associations between the gene groups and diseases were found. The analysis
      revealed associations between vitiligo and diseases such as lichen planus, limb
      girdle muscular dystrophy type 2B, and facioscapulohumeral muscular dystrophy.
      Additionally, the gene groups with an altered expression pattern are
      participating in processes such as cell death, survival and signaling,
      inflammation, and oxidative stress. In conclusion, vitiligo is rather a systemic
      than a local skin disease; the findings from an enormous amount of RNA sequencing
      data support the previous findings about vitiligo and should be further analyzed.

PMID- 27047920
TI  - A Case of a Cellular Neurothekeoma Presenting with Headaches and Review of the
      Literature.
AB  - A 12-year-old female presented with a 1-year history of a slow-growing lesion on
      the frontal scalp. The patient reported intermittent headaches increasing in
      frequency localized under the lesion. Physical exam revealed a firm, fixed, 5-mm
      orange-pink papule on the right frontal scalp. Excisional biopsy was performed
      using a 6-mm punch biopsy, after which the patient reported a cessation of
      headaches. Histopathology showed a diffuse proliferation of spindled and
      epithelioid cells within the superficial and deep reticular dermis demonstrating
      a nested as well as fascicular growth pattern. There was also focal myxoid dermal
      change. Immunohistochemical staining showed the tumor to be strongly positive for
      NK1C3 and negative for S-100. A diagnosis of cellular neurothekeoma was made.
      Cellular neurothekeomas are slow-growing, asymptomatic nodules that most
      frequently appear on the head and neck of young adults. Cellular neurothekeomas
      rarely present with symptoms beyond mild tenderness upon palpation. Our case
      represents a unique presentation of a neurothekeoma of the scalp with complaint
      of headaches, previously unpublished in the literature. 

PMID- 27047921
TI  - Coexpression of SOX10/CD271 (p75(NTR)) and beta-Galactosidase in Large to Giant
      Congenital Melanocytic Nevi of Pediatric Patients.
AB  - BACKGROUND: Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can
      transform into melanoma. However, this development is impeded in the majority of
      cases and mostly affects patients with large or giant CMNs. METHODS: To elucidate
      mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were
      investigated for p-ERK and senescence markers by immunohistochemistry and for
      SOX10/CD271 (p75(NTR)) by immunofluorescence. CMN cells were cultivated, and MTT
      assays were performed for evaluating cell viability. Mutation status for NRAS and
      BRAF was performed by real-time PCR. RESULTS: 13 CMNs (from patients aged 0.5
      11.8 years, mean: 2.7) showed immunoreactivity for SOX10/CD271 (p75(NTR)) in
      34.2%. p-ERK was immunoreactive in 80% (4/5); beta-galactosidase was
      significantly stronger expressed in CMNs compared to melanocytic nevi of patients
      over 70 years (p = 0.0085). The 5 CMN cultures were immunoreactive for
      SOX10/CD271 (p75(NTR)) in 36.7%. By silencing SOX10 by siRNA in 2 CMN cell
      cultures, cell viability decreased significantly. NRAS(Q61K) mutation was found
      in 91.7% (11/12) and BRAF(V600E) in 6.3% of all analyzable CMNs (1/16).
      CONCLUSIONS: Oncogene-induced senescence might prevent malignant transformation
      through activation of the mitogen-activated protein kinase pathway. SOX10 is
      necessary for the viability of human CMN cell cultures and may be responsible for
      clinical changes during aging.

PMID- 27047922
TI  - Nodular Mucinosis of the Breast in a Male: Reassessment of Diagnostic Criteria
      and Proposal for Its Classification as a Soft Tissue Tumor in the
      Myofibroblastoma and Spindle Cell Lipoma Spectrum.
AB  - Nodular mucinosis of the breast (NMB) is a rare entity with only a few cases
      described in the literature, most of them in young girls. All cases are located
      in the nipple and areolar area and microscopically consist of a multinodular
      myxoid mesenchymal proliferation. Bands of sclerotic collagen containing
      preexisting breast ducts and abundant vascularization are other features typical
      of NMB. No relation to Carney complex has been reported, and an indolent behavior
      is the rule in all patients. We present a case of NMB occurring in the nipple of
      a 46-year-old man and analyze the clinicopathological features of the other cases
      of NMB reported in the English literature, concluding that two of them most
      likely correspond to trauma-induced cutaneous focal mucinosis of the mammary
      areola. Finally, we review diagnostic criteria for NMB and elaborate an
      ontogenetic hypothesis based on both its morphological resemblance to
      myofibroblastoma and its immunohistochemical profile. 

PMID- 27047924
TI  - Michel's Transport Medium as an Alternative to Liquid Nitrogen for PCR Analysis
      of Skin Biopsy Specimens.
AB  - Formalin fixation and paraffin embedding are standard procedures for
      histopathological diagnosis and allow long-term archiving of tissue specimens.
      The cross-linking properties of formalin cause fragmentation of nucleic acids and
      reduce the sensitivity of PCR analysis. Michel's medium is a well-established
      transport medium used by dermatologists for biopsy transport to maintain tissue
      fixed immunoreactants prior to direct immunofluorescence and immunoelectron
      microscopy. Here we report that Michel's medium also allows short-term
      preservation of DNA for PCR analysis and permits amplification of amplicons
      larger than 1 kb. Therefore, Michel's medium appears to be a reserve medium for
      performing PCR when no other samples are available. 

PMID- 27047923
TI  - Adolescent Onset of Localized Papillomatosis, Lymphedema, and Multiple Beta
      Papillomavirus Infection: Epidermal Nevus, Segmental Lymphedema Praecox, or
      Verrucosis? A Case Report and Case Series of Epidermal Nevi.
AB  - Herein, we report the case of a 12-year-old female who noted the recent onset of
      an oval, circumscribed, 10-cm papillomatous plaque affecting the thigh and vulva
      that showed histologic signs of lymphedema without evidence of secondary
      lymphedema. The sequencing of genes associated with a delayed onset of lymphedema
      or epidermal nevi (EN) - GATA2 and GJC2, and HRAS and KRAS, respectively - showed
      wild-type alleles. Polymerase chain reaction for human papillomavirus (HPV) DNA
      demonstrated infections with 15 HPV genotypes. Evidence of productive HPV
      infection, HPV capsid expression, and cytopathic changes was detected. At the 6
      month follow-up, no evidence of recurrence was found after complete excision. The
      analysis of a consecutive series of 91 EN excision specimens revealed that 76%
      exhibited histologic evidence of lymphostasis. Notably, multiple acrochordon-like
      EN, which most closely resembled this case, showed similar signs of localized
      lymphedema. The late onset and evidence of lymphedema favors the diagnosis of
      congenital unisegmental lymphedema. However, the clinical findings and epidermal
      changes point to the diagnosis of EN. Moreover, localized verrucosis also
      accurately describes this patient's cutaneous findings. Based on the above
      evidence, we postulate that an abnormal development of lymphatics may play a
      primary role in the pathogenesis of some types of EN and facilitate productive
      HPV infection. 

PMID- 27047925
TI  - Staphylococcal Scalded Skin Syndrome in an Adult on Chemotherapy.
AB  - Staphylococcal scalded skin syndrome is a toxin-mediated, epidermolytic condition
      that uncommonly affects adults. A 51-year-old man receiving chemotherapy for
      leukemia presented with a large geographic erosion with superficial sloughing and
      multiple smaller lesions elsewhere. Biopsy revealed complete subcorneal splitting
      with multiple detached fragments of normal-appearing stratum corneum with
      fragments of attached acantholytic granular keratinocytes. Mild epidermal
      dysmaturation was also noted. Based on these findings, the patient was started on
      oral cephalexin, topical mupirocin, and topical clobetasol. His lesions improved
      significantly over the course of 1 week. 

PMID- 27047926
TI  - Cervicofacial Botryomycosis: Is Atopic Dermatitis a Predisposing Factor?
AB  - BACKGROUND: Botryomycosis is a rare infectious disease which usually affects the
      skin. The low virulence of the bacteria tending to form grains and the immune
      status of the host are important factors in the development of the disease.
      METHODS: We report a case of cervicofacial botryomycosis and review the current
      literature. RESULTS: A 47-year-old male with a long history of moderate-to-severe
      atopic dermatitis presented with painful and suppurative nodules of the head and
      neck. A skin biopsy revealed granules consisting of Gram-positive bacterial
      colonies in a blossom-like assembly in the center and an eosinophilic rim in the
      periphery, which are pathognomonic features of botryomycosis. The lesions
      responded well to systemic antibiotics; however, they rapidly relapsed upon
      cessation of the treatment. CONCLUSIONS: We highlight the well-defined histologic
      features and recall an almost forgotten disease. We review common predisposing
      conditions and present evidence that atopic dermatitis might be an additional
      predisposing factor.

PMID- 27047927
TI  - Perineural Invasion in the Absence of Malignancy: Report of Two Cases and Review
      of the Literature.
AB  - Perineural invasion is usually associated with invasion of the perineural space
      by malignant tumors. In this report, we describe 2 cases of perineural
      infiltration by benign-appearing epithelial cells in the skin. One case concerns
      a tumor-free reexcision specimen of a basal cell carcinoma and the other one an
      ulceration at the outer ear, consistent with acanthoma fissuratum, without a
      history of a previous excision. This finding was interpreted as a reactive
      process with dislocation of epithelium from the overlying epidermis into the
      perineural space. 

PMID- 27047928
TI  - Cellular Neurothekeoma in a Female with Guillain-Barre Syndrome: A Case Report
      and Review of the Literature.
AB  - Cellular neurothekeoma is a rare cutaneous tumor that occurs more frequently in
      women. A 68-year-old female with a history of left nasal alar basal cell
      carcinoma and Guillain-Barre syndrome presented to the clinic with a 3-mm firm
      skin-colored papule with scattered telangiectasias. Histopathologic examination
      with immunochemistry of the lesion was consistent with cellular neurothekeoma. It
      stained positive for microphthalmia transcription factor and NKI-C3 and negative
      for HMB-45 and S-100. The lesion was excised with 3-mm margins, and no recurrence
      was noted within 1 year of follow-up. We present a case of cellular neurothekeoma
      in a patient with a history of Guillain-Barre syndrome as well as a review of the
      literature. Our case report is unique in that no prior association has been found
      in the literature between cellular neurothekeoma and Guillain-Barre syndrome. 

PMID- 27047929
TI  - Modulation of MCP-1, TGF-beta1, and alpha-SMA Expressions in Granulation Tissue
      of Cutaneous Wounds Treated with Local Vitamin B Complex: An Experimental Study.
AB  - Vitamin B complex can modulate the inflammatory response and activate wound
      healing. However, the action mechanisms involved in this process are still
      unclear. The aim of this study was to evaluate the effects of vitamin B complex
      on the modulation of monocyte chemotactic protein (MCP)-1, transforming growth
      factor (TGF)-beta1, and alpha-smooth muscle actin (alpha-SMA) in granulation
      tissue growth. Cutaneous ulcers on Wistar rats were topically treated with
      vitamin B complex. MCP-1, TGF-beta1, and alpha-SMA expressions were evaluated 24,
      72, and 168 h after the treatment. Inflammatory cells were counted and collagen
      fibril staining was performed. After 24 h, more mononuclear cells (p <= 0.01) and
      a higher MCP-1 (p <= 0.05) and TGF-beta1 (p <= 0.01) expression were observed.
      After 72 h, the number of fibroblasts and mononuclear cells (p <= 0.05) was
      elevated. After 168 h, an increased number of fibroblasts, myofibroblasts, and
      blood vessels (p <= 0.01) as well as a strong intensity of collagen fibril
      staining were seen. At that point, the cells presented a higher TGF-beta1
      expression (p <= 0.05), and the size of the ulcer area was decreased (p <= 0.01).
      We can conclude that vitamin B complex may stimulate a positive modulation of MCP
      1, TGF-beta1, and alpha-SMA expressions in granulation tissue of cutaneous
      ulcers. 

PMID- 27047930
TI  - Wong-Type Dermatomyositis Showing Porokeratosis-Like Changes (Columnar
      Dyskeratosis): A Case Report and Review of the Literature.
AB  - BACKGROUND: Wong-type dermatomyositis (DM) exhibits simultaneous pityriasis rubra
      pilaris (PRP) features. CASE REPORT: A 50-year-old woman presented with a
      heliotrope rash, Gottron's papules, and a poikilodermic, erythematous rash in
      shawl distribution without evidence of muscle weakness. Despite topical
      corticosteroids, the eruption progressed 9 months later to include generalized
      hyperkeratotic follicular papules, islands of sparing, and atrophic macules with
      a collarette of scale suggestive of porokeratosis. Mild dysphonia was the only
      sign of muscle weakness. Serology showed positive ANA. Histopathology revealed
      interface dermatitis with dermal mucin and melanophages, irregular psoriasiform
      hyperplasia, alternating mounds of para- and orthokeratosis, and tiers of
      dyskeratotic cells (columnar dyskeratosis). Systemic corticosteroid therapy was
      not tolerated; acitretin diminished the hyperkeratosis. While hyperpigmentation
      persisted, no progression of cutaneous or muscular symptoms has occurred after 22
      months of follow-up and cessation of the therapy. Overall, her course did not
      differ from the natural history documented in the literature review of Wong-type
      DM. The most similar case also exhibited pseudocornoid lamella changes.
      CONCLUSION: Wong-type DM is a clinicopathologic DM-PRP hybrid that can also
      exhibit porokeratosis-like features best described as columnar dyskeratosis.
      Recognizing these types of lesions in DM is warranted in order to make an
      accurate assessment of their prognostic significance.

PMID- 27047931
TI  - Cutaneous Myopericytoma: A Report of 3 Cases and Review of the Literature.
AB  - Cutaneous myopericytoma is a rarely reported mesenchymal neoplasm with a benign
      biologic behavior. It is seen more commonly in males and typically occurs in
      adults on the distal extremities. To the best of our knowledge, there are only 13
      reports describing 45 cases of cutaneous myopericytoma in the literature. The 3
      cases in this report expand the clinical presentation and reinforce the
      histopathologic features of cutaneous myopericytoma. While the clinical
      presentation in 2 cases (located on the scalp and heel) was in keeping with that
      reported previously of a slow-growing painless firm nodule, the third case,
      located on the dorsal wrist, presented as a scaly keratotic nodule.
      Histopathologic examination of all 3 cases revealed an unencapsulated dermal
      nodule with concentric perivascular arrangement of plump, spindle-shaped myoid
      cells admixed with thin-walled blood vessels. Immunohistochemical staining
      revealed the lesional cells to be actin- (3/3) and caldesmon- (2/3) positive and
      negative for other smooth muscle markers, compatible with perivascular
      myopericytic differentiation. 

PMID- 27047933
TI  - Porokeratoma: A Possible Association with Human Papillomavirus Infection.
AB  - Porokeratoma is a rare, relatively newly described and still unclear entity.
      Here, we describe the case of a 52-year-old male patient who presented with four
      well-defined, verrucous and hyperkeratotic lesions. Microscopically, one of the
      lesions showed acanthopapillomatosis overlying compact orthokeratosis. Prominent
      broad and confluent cornoid lamellae were present, with no granular layer and
      some dyskeratotic keratinocytes. PCR sequencing and in situ hybridization
      revealed the presence of human papillomavirus (HPV) type 16 in the lesion. The
      association of porokeratoma and HPV infection has not previously been reported. 

PMID- 27047934
TI  - Nevus-Associated versus de novo Melanoma: Do They Have Different Characteristics
      and Prognoses?
AB  - AIM: The aim of this study was to determine if nevus-associated melanoma differs
      in characteristics and prognosis from de novo melanoma. PATIENTS AND METHODS: The
      study included 118 melanoma patients. Clinical findings were retrospectively
      evaluated. For histopathological parameters, HE sections were reexamined. The
      differentiation between de novo and nevus-associated melanoma was based on the
      histopathological evidence of a precursor nevus. In addition, all analyses were
      repeated in all cases in which nevus-associated melanoma was defined based on
      patient anamnesis. RESULTS: Among all patients, 28 (23.7%) had nevus-associated
      melanoma. Nevus-associated melanoma was most commonly located on the extremities
      (50%), followed by the trunk (25%), whereas de novo melanoma was most commonly
      located in the head and neck region (32.2%), followed by the acral region
      (31.1%). Other clinical findings and histopathological parameters did not differ
      significantly between the two groups (p > 0.05). The findings remained consistent
      following the repeated analysis of all cases in which nevus-associated melanoma
      was defined based on patient anamnesis. CONCLUSIONS: Nevus-associated melanoma
      was most commonly located on the extremities and the trunk, whereas de novo
      melanoma was most commonly located in the head and neck and the acral region.
      Furthermore, nevus-associated melanoma was similar to de novo melanoma in terms
      of prognosis and other disease characteristics.

PMID- 27047935
TI  - Benign Fibrous Histiocytomas of the Oral Mucosa: Report on Three Cases and Review
      of the Literature.
AB  - Benign fibrous histiocytomas (BFH) of the skin are common lesions, although they
      only rarely involve the oral mucosa. This article presents 3 additional cases of
      BFH of the oral mucosa, with a review of previously published cases. Although a
      malignant variant of BFH also exists, the present review focuses only on benign
      lesions. The clinical presentation, diagnosis, histopathological and
      immunohistochemical features of BFH are discussed. According to the present
      analysis, the majority of oral mucosal BFH have occurred in middle-aged and
      elderly patients, with a slight female predilection. Within the oral cavity, BHF
      may occur at any mucosal site, including the lips, tongue, buccal mucosa,
      mandibular and maxillary gingiva as well as the palate. Histopathology is
      essential to diagnose the lesion, while immunohistochemical investigations may be
      utilized to exclude the histopathological differential diagnoses such as juvenile
      xanthogranulomas and nevi. This review also revealed total excision as the
      treatment of choice for BFH, with a very good prognosis and an extremely low rate
      of relapse. 

PMID- 27047936
TI  - The Dilemma of Coexisting Nevoid Hyperkeratosis of the Nipple and Areola in
      Mycosis Fungoides: A Report of Three Cases.
AB  - Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare
      clinicopathological entity showing persistent and strictly localized
      hyperkeratotic lesions of the nipple, areola or both with unknown
      etiopathogenesis. A similar clinical appearance may also be seen in different
      diseases with specific histopathological features. There are a few anecdotal
      reports on the association of NHNA with mycosis fungoides (MF), but they do not
      describe a uniform condition. In this report, we present 3 patients with
      hyperkeratotic lesions of the nipple and areola associated with MF but showing
      different histopathological features. We also review similar cases in the
      literature and discuss possibilities concerning this association. Two of our
      cases represent the association between MF and NHNA without histopathological
      features of MF on the nipple-areola complex. The other case represents
      hyperkeratosis of the nipple and areola with specific histological and
      immunohistochemical features of MF. Hence, we would like to hypothesize that MF
      may involve the nipple and areola and have an appearance similar to NHNA.
      Intriguingly, however, NHNA may occasionally also be seen in association with MF.
      However, this peculiar association requires further explanation. 

PMID- 27047932
TI  - Diagnostic Immunohistochemistry in Cutaneous Neoplasia: An Update.
AB  - Immunohistochemistry (IHC) is an important adjunct in the diagnosis of neoplastic
      skin diseases. In addition to the many established IHC markers currently in use,
      new markers continue to emerge, although their general acceptance and routine
      application requires robust validation. Here, we summarize the most well
      established and commonly used biomarkers along with an array of newer ones
      reported in the past several decades that either demonstrate or hold high
      clinical promise in the field of cutaneous pathology. We also highlight recent
      applications of novel IHC markers in melanoma diagnosis including genetic
      mutation status markers [e.g. BRAF (v-raf murine sarcoma viral oncogene homolog
      B) and NRAS (neuroblastoma RAS viral oncogene homolog)] and an epigenetic
      alteration marker (e.g. 5-hydroxymethylcytosine). We specifically focus on the
      role of IHC in the differential diagnosis of cutaneous lesions that fall under
      the following categories: melanoma, epidermal tumors with an intraepidermal
      epitheliomatous pattern, spindle cell lesions of the dermis, small round blue
      cell tumors of the dermis, and cutaneous adnexal tumors. While IHC is a valuable
      tool in diagnostic dermatopathology, marker selection and interpretation must be
      highly informed by clinical context and the histologic differential diagnosis.
      With rapid progress in our understanding of the genetic and epigenetic mechanisms
      of tumorigenesis, new IHC markers will continue to emerge in the field of
      diagnostic dermatopathology. 

PMID- 27047937
TI  - Psammomatous Melanotic Schwannoma: A Challenging Histological Diagnosis.
AB  - Psammomatous melanotic schwannoma (PMS) is a rare pigmented tumor that can be
      part of the Carney complex. Here, we describe the case of a 35-year-old female
      patient presenting an isolated subcutaneous PMS. Histopathological analysis could
      not formally exclude the malignant nature of the tumor. The challenging
      histological diagnosis and consequently the management of the patient are
      described. 

PMID- 27047938
TI  - Cyclic Stretch Facilitates Myogenesis in C2C12 Myoblasts and Rescues
      Thiazolidinedione-Inhibited Myotube Formation.
AB  - Thiazolidinedione (TZD), a specific peroxisome proliferator-activated receptor
      gamma (PPARgamma) agonist, was developed to control blood glucose in diabetes
      patients. However, several side effects were reported that increased the risk of
      heart failure. We used C2C12 myoblasts to investigate the role of PPARs and their
      transcriptional activity during myotube formation. The role of mechanical stretch
      during myogenesis was also explored by applying cyclic stretch to the
      differentiating C2C12 myoblasts with 10% strain deformation at 1 Hz. The
      myogenesis medium (MM), composed of Dulbecco's modified Eagle's medium with 2%
      horse serum, facilitated myotube formation with increased myosin heavy chain and
      alpha-smooth muscle actin (alpha-SMA) protein expression. The PPARgamma protein
      and PPAR response element (PPRE) promoter activity decreased during MM induction.
      Cyclic stretch further facilitated the myogenesis in MM with increased alpha-SMA
      and decreased PPARgamma protein expression and inhibited PPRE promoter activity.
      Adding a PPARgamma agonist (TZD) to the MM stopped the myogenesis and restored
      the PPRE promoter activity, whereas a PPARgamma antagonist (GW9662) significantly
      increased the myotube number and length. During the myogenesis induction,
      application of cyclic stretch rescued the inhibitory effects of TZD. These
      results provide novel perspectives for mechanical stretch to interplay and rescue
      the dysfunction of myogenesis with the involvement of PPARgamma and its target
      drugs. 

PMID- 27047939
TI  - Wearable Textile Platform for Assessing Stroke Patient Treatment in Daily Life
      Conditions.
AB  - Monitoring physical activities during post-stroke rehabilitation in daily life
      may help physicians to optimize and tailor the training program for patients. The
      European research project INTERACTION (FP7-ICT-2011-7-287351) evaluated motor
      capabilities in stroke patients during the recovery treatment period. We
      developed wearable sensing platform based on the sensor fusion among inertial,
      knitted piezoresistive sensors and textile EMG electrodes. The device was
      conceived in modular form and consists of a separate shirt, trousers, glove, and
      shoe. Thanks to the novel fusion approach it has been possible to develop a model
      for the shoulder taking into account the scapulo-thoracic joint of the scapular
      girdle, considerably improving the estimation of the hand position in reaching
      activities. In order to minimize the sensor set used to monitor gait, a single
      inertial sensor fused with a textile goniometer proved to reconstruct the
      orientation of all the body segments of the leg. Finally, the sensing glove,
      endowed with three textile goniometers and three force sensors showed good
      capabilities in the reconstruction of grasping activities and evaluating the
      interaction of the hand with the environment, according to the project
      specifications. This paper reports on the design and the technical evaluation of
      the performance of the sensing platform, tested on healthy subjects. 

PMID- 27047940
TI  - Mathematical Modeling of Glutathione Status in Type 2 Diabetics with Vitamin B12
      Deficiency.
AB  - Deficiencies in vitamin B12 and glutathione (GSH) are associated with a number of
      diseases including type 2 diabetes mellitus. We tested newly diagnosed Indian
      diabetic patients for correlation between their vitamin B12 and GSH, and found it
      to be weak. Here we seek to examine the theoretical dependence of GSH on vitamin
      B12 with a mathematical model of 1-carbon metabolism due to Reed and co-workers.
      We study the methionine cycle of the Reed-Nijhout model by developing a simple
      "stylized model" that captures its essential topology and whose kinetics are
      analytically tractable. The analysis shows-somewhat counter-intuitively-that the
      flux responsible for the homeostasis of homocysteine is, in fact, peripheral to
      the methionine cycle. Elevation of homocysteine arises from reduced activity of
      methionine synthase, a vitamin B12-dependent enzyme, however, this does not
      increase GSH biosynthesis. The model suggests that the lack of vitamin B12-GSH
      correlation is explained by suppression of activity in the trans-sulfuration
      pathway that limits the synthesis of cysteine and GSH from homocysteine. We
      hypothesize this "cysteine-block" is an essential consequence of vitamin B12
      deficiency. It can be clinically relevant to appreciate that these secondary
      effects of vitamin B12 deficiency could be central to its pathophysiology. 

PMID- 27047941
TI  - Microtubules Are Essential for Mitochondrial Dynamics-Fission, Fusion, and
      Motility-in Dictyostelium discoideum.
AB  - Mitochondrial function is dependent upon mitochondrial structure which is in turn
      dependent upon mitochondrial dynamics, including fission, fusion, and motility.
      Here we examined the relationship between mitochondrial dynamics and the
      cytoskeleton in Dictyostelium discoideum. Using time-lapse analysis, we
      quantified mitochondrial fission, fusion, and motility in the presence of
      cytoskeleton disrupting pharmaceuticals and the absence of the potential
      mitochondria-cytoskeleton linker protein, CluA. Our results indicate that
      microtubules are essential for mitochondrial movement, as well as fission and
      fusion; actin plays a less significant role, perhaps selecting the mitochondria
      for transport. We also suggest that CluA is not a linker protein but plays an
      unidentified role in mitochondrial fission and fusion. The significance of our
      work is to gain further insight into the role the cytoskeleton plays in
      mitochondrial dynamics and function. By better understanding these processes we
      can better appreciate the underlying mitochondrial contributions to many
      neurological disorders characterized by altered mitochondrial dynamics,
      structure, and/or function. 

PMID- 27047943
TI  - Electrocardiographic Changes and Arrhythmia in Fabry Disease.
AB  - Fabry disease is an X-chromosome-linked lysosomal storage disease characterized
      by a deficient activity or, in most males, absence of the enzyme alpha
      galactosidase A (a-Gal A) leading to systemic, primary lysosomal accumulation of
      globotriaosylceramide (Gb3) (1). Recent literature refers to an overall birth
      prevalence of 1:40,000-170,000; however, such data do not allow an estimation on
      an actual patient number suffering from Fabry disease (2). Multisystem morbidity
      commonly develops in childhood and, with progression of the disease, life
      threatening complications often occur in adulthood, including renal failure,
      cardiovascular dysfunction, neuropathy, and stroke (3-6). Life expectancy is
      reduced by an average of 15 years in female patients and 20 years in male
      patients (7, 8). The pathognomonic Gb3 accumulation has been repeatedly observed
      over the past decades by many groups in vascular endothelial and smooth muscle
      cells, cardiomyocytes, cardiac conduction tissue, and valvular fibroblasts (3).
      Although incompletely described, it is likely that inflammatory and neurohormonal
      mechanisms are involved in subsequent cellular and vascular dysfunction, leading
      to tissue ischemia, hypertrophy, and fibrosis (9). Furthermore, recently
      published works on cardiomyocyte dysfunction and conduction tissue involvement
      have suggested that cardiac dysfunction may reflect increased myocardial nitric
      oxide production with oxidative damage of cardiomyocyte myofilaments and DNA,
      causing cell dysfunction and death, and accelerated conduction with prolonged
      refractoriness and electric instability (10, 11). 

PMID- 27047942
TI  - Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin
      Systems.
AB  - In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems
      were confined to bacterial plasmids where they function to mediate the
      maintenance and stability of usually low- to medium-copy number plasmids through
      the post-segregational killing of any plasmid-free daughter cells that developed.
      Their eventual discovery as nearly ubiquitous and repetitive elements in
      bacterial chromosomes led to a wealth of knowledge and scientific debate as to
      their diversity and functionality in the prokaryotic lifestyle. Currently
      categorized into six different types designated types I-VI, type II TA systems
      are the best characterized. These generally comprised of two genes encoding a
      proteic toxin and its corresponding proteic antitoxin, respectively. Under normal
      growth conditions, the stable toxin is prevented from exerting its lethal effect
      through tight binding with the less stable antitoxin partner, forming a non
      lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin
      also plays a role in regulating the expression of the type II TA operon by
      binding to the operator site, thereby repressing transcription from the TA
      promoter. In most cases, full repression is observed in the presence of the TA
      complex as binding of the toxin enhances the DNA binding capability of the
      antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular
      functions such as being mediators of programmed cell death as well as persistence
      or dormancy, biofilm formation, as defensive weapons against bacteriophage
      infections and as virulence factors in pathogenic bacteria. It is thus apparent
      that these antitoxins, as DNA-binding proteins, play an essential role in
      modulating the prokaryotic lifestyle whilst at the same time preventing the
      lethal action of the toxins under normal growth conditions, i.e., keeping the
      proverbial wolves at bay. In this review, we will cover the diversity and
      characteristics of various type II TA antitoxins. We shall also look into some
      interesting deviations from the canonical type II TA systems such as tripartite
      TA systems where the regulatory role is played by a third party protein and not
      the antitoxin, and a unique TA system encoding a single protein with both toxin
      as well as antitoxin domains. 

PMID- 27047944
TI  - Household Food Items Toxic to Dogs and Cats.
AB  - Several foods that are perfectly suitable for human consumption can be toxic to
      dogs and cats. Food-associated poisoning cases involving the accidental ingestion
      of chocolate and chocolate-based products, Allium spp. (onion, garlic, leek, and
      chives), macadamia nuts, Vitis vinifera fruits (grapes, raisins, sultanas, and
      currants), products sweetened with xylitol, alcoholic beverages, and unbaked
      bread dough have been reported worldwide in the last decade. The poisoning
      episodes are generally due to lack of public knowledge of the serious health
      threat to dogs and cats that can be posed by these products. The present review
      aims to outline the current knowledge of common food items frequently involved in
      the poisoning of small animals, particularly dogs, and provides an overview of
      poisoning episodes reported in the literature. 

PMID- 27047945
TI  - Immuno-regulated common markers but different network signatures in two
      associated cancers: evidences from epigenetic treatment.
AB  - BACKGROUND: Networks are now widely accepted inference tools in translational
      oncology. Besides providing agnostic model frameworks for complex data-driven
      clinical problems of diagnostic, therapeutic and prognostic impacts, networks
      mainly support insights, testable hypotheses and decision processes on the basis
      of their topological configurations and connectivity patterns. METHODS: The
      purpose of this study is to emphasize the role of both gene and network
      signatures in two specific cancers. Retinoblastoma (RB) and osteosarcoma are
      associated to some extent. It is known that patients who carry germline mutations
      in the RB1 gene, and who survive RB, are typically at an increased risk of early
      onset second cancers, including osteosarcomas. Gene signatures are widely used,
      but also criticized for their partial lack of reproducibility. Network signatures
      include gene association dynamics by identifying modules or communities in which
      subsets of genes functionally belong. RESULTS: Two cancer cell lines (one per
      cancer type) were subjected to a similar epigenetic treatment regimen, using a
      demethylation agent (DAC, and including similar dose and time course
      administration). A minimal set of shared differentially expressed (DEG) genes was
      identified in cancer-specific cell lines from microarray analyses. However, the
      identified immune signatures were observed to translate into much diversified
      network signatures. CONCLUSIONS: Our evidence is relevant to therapeutic
      developments, indicating that preference should be assigned to the assessment of
      bio-entities in a connected environment rather than considering single entities
      alone.

PMID- 27047946
TI  - Chest CT abnormalities and quality of life: relationship in adult cystic
      fibrosis.
AB  - BACKGROUND: To evaluate the relationship between lung parenchymal abnormalities
      on chest CT and health-related quality of life in adult cystic fibrosis (CF).
      METHODS: The chest CT scans of 101 consecutive CF adults (mean age 27.8+/-7.9, 64
      males) were prospectively scored by two blinded radiologists in consensus using a
      modified Bhalla score. Health-related quality of life was assessed using the
      revised Quittner Cystic Fibrosis Questionnaire (CFQ-R). Multiple regressions were
      performed with each of the CFQ-R domains and all clinical and imaging findings to
      assess independent correlations. RESULTS: There were 18 inpatients and 83
      outpatients. For the cohort of inpatients, CT abnormalities were significantly
      (P<0.005 for all) associated with Respiratory Symptoms (Air Trapping), and also
      with Social Functioning (Consolidation) and Role Functioning (Consolidation). For
      outpatients, CT abnormalities were significantly (P<0.005 for all) associated
      with Respiratory Symptoms (Consolidation) and also with Physical Functioning
      (Consolidation), Vitality (Consolidation, Severity of Bronchiectasis), Eating
      Problems (airway wall thickening), Treatment Burden (Total CT Score), Body Image
      (Severity of Bronchiectasis) and Role Functioning (Tree-in-bud nodules).
      Consolidation was the commonest independent CT predictor for both inpatients
      (predictor for 2 domains) and outpatients (predictor in 3 domains). Several chest
      CT abnormalities excluded traditional measures such as FEV1 and BMI from the
      majority of CFQ-R domains. CONCLUSIONS: Chest CT abnormalities are significantly
      associated with quality of life measures in adult CF, independent of clinical or
      spirometric measurements.

PMID- 27047947
TI  - Analysis of the height dependence of site-specific cancer risk in relation to
      organ mass.
AB  - BACKGROUND: Cancer risks at multiple cancer sites have been shown to correlate
      positively with height. An existing idea is that taller people have more cells
      and thus more prone to mutations that will lead to cancer, and the hypothesis is
      that cancer risk is proportional to the organ mass. In this study we
      quantitatively test this hypothesis. METHODS: We perform an analysis of large
      scale data on the height dependence of site-specific cancer risks. We also
      perform an analysis of the height dependence of measured organ masses. We then
      compare the cancer risk data with the expectations based on the organ mass
      hypothesis. Our study includes 16 cancer sites of women and 14 cancer sites of
      men. RESULTS: For the relative risk (RR) per 10 cm increase in height for cancer
      incidence, the averaged expected value is within the 95% confidence interval (CI)
      of the averaged cancer risk data for 8 out of the 15 cancer sites for which the
      comparison can be made. Also, a large proportion of the sex difference of cancer
      risks for pancreas and lungs could come from the sex difference of the organ
      mass. CONCLUSIONS: The hypothesis that cancer risk is proportional to the organ
      mass partially explains the height dependence of cancer risks. It also helps
      explain the sex difference of cancer risks, especially for pancreas and lungs.

PMID- 27047948
TI  - Thoracic surgical training in Europe: what has changed recently?
AB  - Training in thoracic surgery (TS) traditionally varies amongst countries in
      Europe. The theoretical content of the training, the length of training, the
      amount of self-performed procedures to be done and the definition of training
      units all differ in European countries. However, in the past two decades, several
      initiatives were taken to harmonize TS training in Europe. The purpose of this
      paper is to highlight these initiatives and their impact on today's TS training
      in Europe. 

PMID- 27047950
TI  - Univariate description and bivariate statistical inference: the first step
      delving into data.
AB  - In observational studies, the first step is usually to explore data distribution
      and the baseline differences between groups. Data description includes their
      central tendency (e.g., mean, median, and mode) and dispersion (e.g., standard
      deviation, range, interquartile range). There are varieties of bivariate
      statistical inference methods such as Student's t-test, Mann-Whitney U test and
      Chi-square test, for normal, skews and categorical data, respectively. The
      article shows how to perform these analyses with R codes. Furthermore, I believe
      that the automation of the whole workflow is of paramount importance in that (I)
      it allows for others to repeat your results; (II) you can easily find out how you
      performed analysis during revision; (III) it spares data input by hand and is
      less error-prone; and (IV) when you correct your original dataset, the final
      result can be automatically corrected by executing the codes. Therefore, the
      process of making a publication quality table incorporating all abovementioned
      statistics and P values is provided, allowing readers to customize these codes to
      their own needs. 

PMID- 27047949
TI  - Objective and quantitative assessment of motor function in Parkinson's disease
      from the perspective of practical applications.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder with high
      morbidity because of the coming aged society. Currently, disease management and
      the development of new treatment strategies mainly depend on the clinical
      information derived from rating scales and patients' diaries, which have various
      limitations with regard to validity, inter-rater variability and continuous
      monitoring. Recently the prevalence of mobile medical equipment has made it
      possible to develop an objective, accurate, remote monitoring system for motor
      function assessment, playing an important role in disease diagnosis, home
      monitoring, and severity evaluation. This review discusses the recent development
      in sensor technology, which may be a promising replacement of the current rating
      scales in the assessment of motor function of PD. 

PMID- 27047951
TI  - Biological samples transportation by drones: ready for prime time?

PMID- 27047952
TI  - Getting to the core of fibrosis: targeting redox imbalance in aging.

PMID- 27047953
TI  - Radiotherapy: killing with complement.

PMID- 27047954
TI  - Combination therapy with TLR7 agonist and radiation is effective for the
      treatment of solid cancer.

PMID- 27047955
TI  - Mutations at the splice sites of exon 14 of MET gene: a new target for
      sarcomatoid carcinomas?

PMID- 27047956
TI  - Has MET met its match?

PMID- 27047957
TI  - Management of lower pole renal stones: the devil is in the details.
AB  - Shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and minimally
      invasive percutaneous nephrolithotomy (MIP) are highly effective treatment
      options for lower pole stones up to 2 cm. Selecting the best treatment modality
      represents a controversial area in urology, because each treatment methods have
      their own advantages and disadvantages. Donaldson and co-workers have recently
      published a very comprehensive review and meta-analysis to compare the benefits
      and harms of SWL, RIRS and PNL techniques. 

PMID- 27047958
TI  - Assessing the cardiovascular risk of hormonal therapy in patients with prostate
      cancer.

PMID- 27047959
TI  - Combination therapy for metastatic renal cell carcinoma.
AB  - Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of
      the serial administration of single agents. Combinations of VEGF and mTOR
      inhibitors have been disappointing in previous randomized trials. However, the
      combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as
      FGF receptors, and everolimus demonstrated promising results in a randomized
      phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and
      programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation
      of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte
      antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with
      the development of predictive biomarkers and agents inhibiting novel therapeutic
      targets may provide much needed advances in this still largely incurable disease.

PMID- 27047960
TI  - A novel role of hepatic epithelial transforming growth factor-beta signaling in
      cholangiocarcinogenesis.

PMID- 27047961
TI  - Mining of single nucleotide polymorphisms in the 3' untranslated region of liver
      cancer-implicated miR-122 target genes.

PMID- 27047962
TI  - Human Umbilical Cord Mesenchymal Stem Cells Therapy in Cyclophosphamide-Induced
      Premature Ovarian Failure Rat Model.
AB  - Premature ovarian failure (POF) is one of the most common causes of infertility
      in women. In our present study, we established cyclophosphamide- (CTX-) induced
      POF rat model and elucidated its effect on ovarian function. We detected the
      serum estrogen, follicle stimulating hormone, and anti-Mullerian hormone of mice
      models by ELISA and evaluated their folliculogenesis by histopathology
      examination. Our study revealed that CTX administration could severely disturb
      hormone secretion and influence folliculogenesis in rat. This study also detected
      ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL) and
      demonstrated marked ovarian cells apoptosis in rat models following CTX
      administration. In order to explore the potential of human umbilical cord
      mesenchymal stem cells (UCMSCs) in POF treatment, the above indexes were used to
      evaluate ovarian function. We found that human UCMSCs transplantation recovered
      disturbed hormone secretion and folliculogenesis in POF rat, in addition to
      reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by
      fluorescence in situ hybridization (FISH). The results manifested that the
      transplanted human UCMSCs could reside in ovarian tissues and could survive for a
      comparatively long time without obvious proliferation. Our present study provides
      new insights into the great clinical potential of human UCMSCs in POF treatment. 

PMID- 27047963
TI  - Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial
      Defect Model.
AB  - Absorbable extracellular matrix (ECM) membrane has recently been used as a
      barrier membrane (BM) in guided tissue regeneration (GTR) and guided bone
      regeneration (GBR). Absorbable BMs are mostly based on collagen, which is more
      biocompatible than synthetic materials. However, implanted absorbable BMs can be
      rapidly degraded by enzymes in vivo. In a previous study, to delay degradation
      time, collagen fibers were treated with cross-linking agents. These compounds
      prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit
      delayed tissue integration. In addition, the remaining cross-linker could induce
      inflammation. Here, we attempted to overcome these problems using a natural ECM
      membrane. The membrane consisted of freshly harvested porcine pericardium that
      was stripped from cells and immunoreagents by a cleaning process. Acellular
      porcine pericardium (APP) showed a bilayer structure with a smooth upper surface
      and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18
      0.35 mm) but with excellent mechanical properties. Tensile strength of APP was
      14.15 +/- 2.24 MPa. In in vivo experiments, APP was transplanted into rabbit
      tibia. The biocompatible material was retained for up to 3 months without the
      need for cross-linking. Therefore, we conclude that APP could support
      osteogenesis as a BM for up to 3 months.

PMID- 27047964
TI  - Analysis of Shear Bond Strength and Morphology of Er:YAG Laser-Recycled Ceramic
      Orthodontic Brackets.
AB  - OBJECTIVE: The aim of this study was to compare the recycling of deboned ceramic
      brackets via an Er:YAG laser or via the traditional chairside processing methods
      of flaming and sandblasting; shear bond strength and morphological changes were
      evaluated in recycled brackets versus new brackets. MATERIALS AND METHODS: 3M
      Clarity Self-Ligating Ceramic Brackets with a microcrystalline base were divided
      into groups subjected to flaming, sandblasting, or exposure to an Er:YAG laser.
      New ceramic brackets served as a control group. Shear bond strengths were
      determined with an Electroforce test machine and tested for statistical
      significance through analysis of variance. Morphological examinations of the
      recycled ceramic bracket bases were conducted with scanning electron microscopy
      and confocal laser scanning microscopy. Residue on the bracket base was analyzed
      with Raman spectroscopy. RESULTS: Faded, dark adhesive was left on recycled
      bracket bases processed via flaming. Adhesive was thoroughly removed by both
      sandblasting and exposure to an Er:YAG laser. Compared with new brackets, shear
      bond strength was lower after sandblasting (p < 0.05), but not after exposure to
      an Er:YAG laser. The Er:YAG laser caused no damage to the bracket. CONCLUSION:
      Er:YAG lasers effectively remove adhesive from the bases of ceramic brackets
      without damaging them; thus, this method may be preferred over other recycling
      methods.

PMID- 27047965
TI  - In Vivo Laser Scanning Confocal Microscopy of Human Meibomian Glands in Aging and
      Ocular Surface Diseases.
AB  - Meibomian glands (MGs) play a crucial role in the ocular surface homeostasis by
      providing lipids to the superficial tear film. Their dysfunction destabilizes the
      tear film leading to a progressive loss of the ocular surface equilibrium and
      increasing the risk for dry eye. In fact, nowadays, the meibomian gland
      dysfunction is one of the leading causes of dry eye. Over the past decades, MGs
      have been mainly studied by using meibography, which, however, cannot image the
      glandular structure at a cellular level. The diffusion of the in vivo laser
      scanning confocal microscopy (LSCM) provided a new approach for the structural
      assessment of MGs permitting a major step in the noninvasive evaluation of these
      structures. LSCM is capable of showing MGs modifications during aging and in the
      most diffuse ocular surface diseases such as dry eye, allergy, and autoimmune
      conditions and in the drug-induced ocular surface disease. On the other hand,
      LSCM may help clinicians in monitoring the tissue response to therapy. In this
      review, we summarized the current knowledge about the role of in vivo LSCM in the
      assessment of MGs during aging and in the most diffuse ocular surface diseases. 

PMID- 27047966
TI  - Drought Tolerance Is Correlated with the Activity of Antioxidant Enzymes in
      Cerasus humilis Seedlings.
AB  - Cerasus humilis, grown in the northern areas of China, may experience water
      deficit during their life cycle, which induces oxidative stress. Our present
      study was conducted to evaluate the role of oxidative stress management in the
      leaves of two C. humilis genotypes, HR (drought resistant) and ND4 (drought
      susceptible), when subjected to a long-term soil drought (WS). The HR plants
      maintained lower membrane injury due to low ROS and MDA accumulation compared to
      ND4 plants during a long-term WS. This is likely attributed to global increase in
      the activities of superoxide dismutase (SOD) isoenzymes and enzymes of the
      ascorbate-glutathione (AsA-GSH) cycle and maintenance of ascorbate (AsA) levels.
      Consistent closely with enzymes activities, the expression of cytosolic ascorbate
      peroxidase (cAPX) and dehydroascorbate reductase (DHAR) followed a significant
      upregulation, indicating that they were regulated at the transcriptional level
      for HR plants exposed to WS. In contrast, ND4 plants exhibited high ROS levels
      and poor antioxidant enzyme response, leading to enhanced membrane damage during
      WS conditions. The present study shows that genotypic differences in drought
      tolerance could be likely attributed to the ability of C. humilis plants to
      induce antioxidant defense under drought conditions. 

PMID- 27047967
TI  - Larvicidal, Biological and Genotoxic Effects, and Temperature-Toxicity
      Relationship of Some Leaf Extracts of Nerium oleander (Apocynaceae) on Culex
      pipiens (Diptera: Culicidae).
AB  - BACKGROUND: The present study was undertaken to study the larvicidal activity of
      different extracts of Nerium oleander leaves, and post-treatment temperature-
      toxicity relationship of these extracts against Culex pipiens. Further, the most
      potent extract was used to evaluate its biological and genotoxic activities.
      METHODS: Crude extracts of N. oleander leaves were prepared using water,
      chloroform, acetone and diethyl ether as solvents. Extraction was carried out
      using soxhlet apparatus. Bioassay test was carried out on the larvae, and the
      LC50 of each extract was determined. Thus, newly hatched first instar larvae were
      treated, and the mortality count was recorded daily till pupation (accumulated
      mortality). The LC50 of diethyl ether extract, as the most potent extract, was
      used for the further biological and genotoxic studies. RESULTS: The results
      obtained indicated that diethyl ether extract of N. oleander leaves was the most
      potent extract, with LC50 of 10500 mg/l. The toxicity of the four extracts, using
      the LC50, at 10  degrees C was higher than that at 35  degrees C. The LC50 of
      diethyl ether extract significantly decreased the larval duration, pupal
      duration, percentage of pupation, percentage of adult emergence, longevity of
      females, fecundity, and oviposition activity index, whereas the growth index and
      the percentage of development per day of larvae and pupae were significantly
      increased compared to non-treated insects. Moreover, treatment with this extract
      induced significant dominant lethality in both male and female adults.
      CONCLUSION: It appears that diethyl ether extract of N. oleander leaves is
      potential control agent to Cx. pipiens.

PMID- 27047968
TI  - Assessment of Recombination in the S-segment Genome of Crimean-Congo Hemorrhagic
      Fever Virus in Iran.
AB  - BACKGROUND: Crimean-Congo Hemorrhagic Fever Virus (CCHFV) belongs to genus
      Nairovirus and family Bunyaviridae. The main aim of this study was to investigate
      the extent of recombination in S-segment genome of CCHFV in Iran. METHODS:
      Samples were isolated from Iranian patients and those available in GenBank, and
      analyzed by phylogenetic and bootscan methods. RESULTS: Through comparison of the
      phylogenetic trees based on full length sequences and partial fragments in the S
      segment genome of CCHFV, genetic switch was evident, due to recombination event.
      Moreover, evidence of multiple recombination events was detected in query
      isolates when bootscan analysis was used by SimPlot software. CONCLUSION: Switch
      of different genomic regions between different strains by recombination could
      contribute to CCHFV diversification and evolution. The occurrence of
      recombination in CCHFV has a critical impact on epidemiological investigations
      and vaccine design.

PMID- 27047969
TI  - Ecological Status of Phlebotomine Sandflies (Diptera: Psychodidae) in Rural
      Communities of Northeastern Algeria.
AB  - BACKGROUND: Algeria is among the most affected Mediterranean countries by
      leishmaniasis due to its large geographic extent and climatic diversity. The
      current study aimed to determine the ecological status (composition and
      diversity) of phlebotomine sandfly populations in the region of Oum El Bouaghi
      (Northeast Algeria). METHODS: An entomological survey was conducted during the
      period May-October 2010 in rural communities of Oum El Bouaghi. Catches of
      sandflies were carried out using sticky traps in both domestic and peri-domestic
      environments of 16 sites located beneath two bioclimatic areas, sub-humid and
      semi-arid. Most of these sites have visceral and/or cutaneous leishmaniasis
      cases. RESULTS: A total of 1,363 sandflies were captured and identified. They
      belong to two genera, Phlebotomus and Sergentomyia, and five species. The species
      Phlebotomus perniciosus, P. perfiliewi and Sergentomyia minuta were constants.
      Phlebotomus longicuspis was common and P. papatasi was accidental in the study
      sites. P. perniciosus and P. perfiliewi are the two possible species that
      contribute in leishmaniasis transmission across the study area due to their high
      densities (96 and 49 specimens/m(2)/night, respectively); these two species
      dominate other species in all study sites. CONCLUSION: Findings emphasize the key
      role played by P. perniciosus, P. perfiliewi and S. minuta in outlining site
      similarities based on sandfly densities. The study confirms that the more
      susceptible sites to leishmaniasis, which hold high densities of these sandflies,
      were located south of the study area under a semi-arid climate.

PMID- 27047970
TI  - Seasonal and Physiological Variations of Phlebotomus papatasi Salivary Gland
      Antigens in Central Iran.
AB  - BACKGROUND: Sand fly saliva helps parasite establishment and induce immune
      responses in vertebrate hosts. In the current study, we investigated the
      modulation of Phlebotomus papatasi salivary gland antigen expression by seasonal
      and biological factors. METHODS: Sand flies were grouped according to
      physiological stages such as unfed, fed, semi-gravid, gravid, parous,
      nulliparous, infected or non-infected with Leishmania major and based on the
      season in which they were collected. Salivary gland antigens (SGAs) were analyzed
      using SDS-PAGE and the antibody response against SGAs in Rhombomys opimus was
      determined by ELISA and Western blot. RESULTS: The highest protein content was
      found in the salivary glands of unfed sand flies. The saliva content was higher
      in parous compared to nulliparous, in summer compared to spring, and in
      Leishmania-infected compared to non-infected flies. The salivary gland lysate
      (SGL) electrophoretic pattern variations were observed among sand flies with
      various physiological stages particularly from 4-9 protein bands of 14-70 kDa.
      The SGL of unfed and gravid flies had extra protein bands compared to fed and
      semi-gravid sand flies. There was missing protein bands in SGL of parous compared
      to nulliparous; and in summer compared to spring collected flies. Rhombomys
      opimus serum reacted strongly with an antigenic band of around 28 kDa in the SGL
      of all sand fly groups. CONCLUSION: Certain biological and environmental
      characteristics of wild populations of vector sand flies affect the protein
      content and antigenicity of saliva. This might have an important implication in
      the design of vector-based vaccines.

PMID- 27047971
TI  - Ticks and Fleas Infestation on East Hedgehogs (Erinaceus concolor) in Van
      Province, Eastern Region of Turkey.
AB  - BACKGROUND: Ixodid ticks (Acari: Ixodidae) and fleas (Siphonaptera) are the major
      vectors of pathogens threatening animals and human healths. The aim of our study
      was to detect the infestation rates of East Hedgehogs (Erinaceus concolor) with
      ticks and fleas in Van Province, eastern region of Turkey. METHODS: We examined
      fleas and ticks infestation patterns in 21 hedgehogs, collected from three
      suburbs with the greater of number gardens. In order to estimate flea and tick
      infestation of hedgehogs, we immobilized the ectoparasites by treatment the body
      with a insecticide trichlorphon (Neguvon(r)-Bayer). RESULTS: On the hedgehogs, 60
      ixodid ticks and 125 fleas were detected. All of the ixodid ticks were
      Rhipicephalus turanicus and all of the fleas were Archaeopsylla erinacei.
      Infestation rate for ticks and fleas was detected 66.66 % and 100 %,
      respectively. CONCLUSION: We detected ticks (R. turanicus) and fleas (A.
      erinacei) in hedgehogs at fairly high rates. Since many ticks and fleas species
      may harbor on hedgehogs and transmit some tick-borne and flea-borne patogens,
      this results are the important in terms of veterinary and public health.

PMID- 27047972
TI  - Simultaneous Morphological and Molecular Characterization of Tatera indica in
      Southwestern Iran.
AB  - BACKGROUND: Interest in Tatera indica rodent arises mostly because it is believed
      that this species is survived among four subspecies reported from Iran, two of
      which exist in Khuzestan Province. In addition, it might has a role as reservoir
      hosts of zoonotic cutaneous leishmaniasis in the transmission of Leishmania major
      in some of the widespread Asian foci including southwestern Iran. METHODS:
      Diagnostic morphological and molecular markers for T. indica were sought by
      characterizing from individual specimens, such as some taxonomic features and
      mitochondrial cytochrome b gene that had previously proven useful for the
      taxonomy of rodents. Wild rodents were caught using live wooden and wire traps.
      The specimens were identified morphologically using external criteria and
      molecularly by sequencing of Cyt b gene and phylogenetic analyses. RESULTS: Forty
      one T. indica were collected and identified morphologically in Khuzestan
      Province, Iran. Two morphotypes of T. indica were found and classified but
      sequencing and phylogenetic analyses of mitochondrial Cyt b gene did not support
      any subspecies between two morphotypes of T. indica. Because all 21 sequences of
      both morphotypes of T. indica had no variation with only one common and novel
      haplotype (GenBank accession No KP001566). CONCLUSION: This is the first time
      that T. indica was characterized molecularly in Iran. There is no molecular
      evidence for T. indica morphotypes or subspecies, and so a population genetics
      approach using several polymorphic genes might be employed using species-specific
      molecular markers. In addition, more specimens of T. indica species in large
      geographical locations should be tested.

PMID- 27047973
TI  - Physicochemical Characteristics of Larval Habitat Waters of Mosquitoes (Diptera:
      Culicidae) in Qom Province, Central Iran.
AB  - BACKGROUND: Mosquitoes lay eggs in a wide range of habitats with different
      physicochemical parameters. Ecological data, including physicochemical factors of
      oviposition sites, play an important role in integrated vector management. Those
      data help the managers to make the best decision in controlling the aquatic
      stages of vectors especially using source reduction. METHODS: To study some
      physicochemical characteristics of larval habitat waters, an investigation was
      carried out in Qom Province, central Iran, during spring and summer 2008 and
      2009. Water samples were collected during larval collection from ten localities.
      The chemical parameters of water samples were analyzed based on mg/l using
      standard methods. Water temperature ( degrees C), turbidity (NTU), total
      dissolved solids (ppm), electrical conductivity (MUS/cm), and acidity (pH) were
      measured using digital testers. Thermotolerant coliforms of water samples were
      analyzed based on MPN/100ml. Data were assessed by Kruskal-Wallis test and
      Spearman Correlation analysis. RESULTS: In total, 371 mosquito larvae were
      collected including 14 species representing four genera. Some physicochemical
      parameters of water in Emamzadeh Esmail, Qomrood, Qom City, and Rahjerd showed
      significant differences among localities (P< 0.05). The physicochemical and
      microbial parameters did not show any significant differences among different
      species (P> 0.05). There was no significant correlation between the abundance of
      larvae and the different physicochemical and microbial parameters (P> 0.05).
      CONCLUSION: The means of EC, TDS, and phosphate of localities and species were
      remarkably higher than those of the previous studies. Other parameters seem to be
      in the range of other investigations.

PMID- 27047974
TI  - Application of Flumethrin Pour-On on Reservoir Dogs and Its Efficacy against Sand
      Flies in Endemic Focus of Visceral Leishmaniasis, Meshkinshahr, Iran.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is one of the most important parasitic
      zoonotic diseases in the world. Domestic dogs are the main domestic reservoirs of
      VL in endemic foci of Iran. Various methods, including vaccination, treatment of
      dogs, detection and removal of infected dogs have different results around the
      world. General policy on control of canine visceral leishmaniasis is protection
      of them from sand fly bites. The aim of this study was evaluation of pour-on
      application of flumethrin on dogs against blood-feeding and mortality of field
      caught sand flies. METHODS: Once every 20 days from May untill September 2013,
      the treated and control dogs were exposed with field caught sandflies for 2 hours
      under bed net traps. After the exposure time, both alive and dead sand flies were
      transferred in netted cups to the laboratory. The mortality rate of them was
      assessed after 24 hours. The blood-fed or unfed conditions were determined 2
      hours after exposure to the dogs under stereomicroscope. RESULTS: The blood
      feeding index was varied from 12.0 to 25.0 % and 53.0 to 58.0 % for treated and
      control dogs respectively (P< 0.0001). The blood feeding inhibition was 75.0-87.0
      % and 41.0-46.0 % for the control and treated dogs (P< 0.0001), respectively.The
      total mortality rate was 94.0-100 % and 19.0-58.0 % respectively for the treated
      and control groups (P< 0.001). CONCLUSTION: Application of pour-on flumethrin on
      dogs caused 90-100 % mortality until 2.5 month and inhibited the blood-feeding of
      sand flies.

PMID- 27047975
TI  - A Comparative Study of Serum, Urine and Saliva Using rk39 Strip for the Diagnosis
      of Visceral Leishmaniasis.
AB  - BACKGROUND: Immunochromatographic based rk39 antibody detection test became
      popular for the diagnosis of visceral leishmaiasis (VL) because of high
      sensitivity, rapidity, easy to interpret, and cost effectiveness. However, false
      positive result after complete cure of the patients is the major limitation with
      this test. The aim of the study to access the usefulness of non-invasive samples
      i.e. urine and saliva by rk39 test for the diagnosis of visceral leishmaniasis in
      comparison to serum. METHODS: Seventy two clinically suspected VL patients were
      enrolled in the study among which 61 cases were confirmed as VL and 11 cases were
      included in the control group. Serum, urine, and saliva samples of all the cases
      were tested for rk39 dip stick test. RESULTS: Urine and saliva both were equally
      sensitive as serum for the diagnosis kala-azar. In the control group, rk39
      antibody test was negative in 10 cases out 11 (91%) with saliva in comparison to
      4 cases with serum (36%), thereby found to be more specific. CONCLUSION: Saliva
      sample found to be highly reliable for the diagnosis of VL cases by rk39 test.
      The test with saliva sample showed less false positive result in comparison to
      serum sample, thereby can be used an adjunct with serum sample for the diagnosis
      of kala-azar in endemic areas.

PMID- 27047976
TI  - Occult Dirofilariosis in Dogs of North Eastern Region in India.
AB  - BACKGROUND: The North Eastern Region in India is endemic for canine heartworm
      disease but in clinics accurate diagnosis is some times difficult. The aim of the
      present study was to determine the prevalence of occult infections for heartworm
      disease in canine in two geographical regions of North Eastern India. METHODS: A
      total of 782 numbers of three categories of dogs namely, working dogs of military
      and paramilitary forces, pet dogs and stray dogs were screened for the presence
      of heartworm infection from August 2011 to July, 2012 in Guwahati (Assam) and
      Aizawl (Mizoram). Conventional, immunological and molecular techniques were
      followed for this epidemiological study. The criteria to determine the occult
      heartworm cases were based on the differences between heartworm positive cases in
      PCR test and antigen ELISA test. RESULTS: The findings revealed an overall 22.69
      percent occult case. The working dogs had highest prevalence (60%) followed by
      pet (29.16%) and stray dogs (17.75%). CONCLUSION: The highest percentage of
      occult heartworm infection was present in working dogs maintained under military
      or paramilitary forces.

PMID- 27047977
TI  - Record of Tropical Rat Mite, Ornithonyssus bacoti (Acari: Mesostigmata:
      Macronyssidae) from Domestic and Peridomestic Rodents (Rattus rattus) in
      Nilgiris, Tamil Nadu, India.
AB  - BACKGROUND: Tropical rat mite (Ornithonyssus bacoti) is reported from many parts
      of the world and is considered important in transmitting rickettsial pathogens.
      There have been scanty reports on prevalence of this parasite from India.
      Following a recent report of O. bacoti infestation in a laboratory mice colony
      from Nilgiris, Tamil Nadu, India, attempts were made to detect the parasite in
      its natural reservoir, ie the domestic and peridomestic rats (Rattus rattus).
      METHODS: The National Centre for Disease Control, Coonoor is involved in
      screening plague in domestic and peridomestic rats in Nilgiris and erstwhile
      plague endemic areas of Southern India. The parasite samples were identified
      based on the morphological characteristics attributable to O. bacoti and as per
      description of published literature. RESULTS: Seven mite samples identified as O.
      bacoti based on morphological characteristics were isolated incidentally from
      domestic and peridomestic rodents in and around the hilly districts of Nilgiris,
      Southern India, during the routine plague surveillance programme. The
      identification was based on the morphological characteristics attributable to O.
      bacoti observed under a low power microscope. CONCLUSION: In India, this is
      probably the first record of isolation of O. bacoti from domestic and
      peridomestic rodents. Prevalence of such parasite in domestic and peridomestic
      rats necessitates further investigation on monitoring and surveillance of
      rickettsial diseases in the locality, as these parasites are considered to be
      potential vector of transmitting rickettsial pathogens.

PMID- 27047978
TI  - Species Composition and Ecological Aspects of Immature Mosquitoes (Diptera:
      Culicidae) in Bromeliads in Urban Parks in the City of Sao Paulo, Brazil.
AB  - BACKGROUND: Bromeliads can be epiphytic, terrestrial or saxicolous and use
      strategies to allow water to be retained in their leaf axils, where various
      arthropods can be found. These include mosquitoes, whose larvae are the most
      abundant and commonly found organisms in the leaf axils. The objective of this
      study was to look for immature forms of mosquitoes (the larval and pupal stages)
      in bromeliads in municipal parks in Sao Paulo and to discuss the ecological and
      epidemiological importance of these insects. METHODS: From October 2010 to July
      2013, immature mosquitoes were collected from bromeliads in 65 municipal parks in
      the city of Sao Paulo, Brazil, using suction samplers. The immature forms were
      maintained until adult forms emerged, and these were then identified
      morphologically. RESULTS: Two thousand forty-two immature-stage specimens
      belonging to the genera Aedes, Culex, Trichoprosopon, Toxorhynchites, Limatus and
      Wyeomyia were found in bromeliads in 15 of the 65 parks visited. Aedes albopictus
      was the most abundant species (660 specimens collected), followed by Culex
      quinquefasciatus (548 specimens) and Cx. (Microculex) imitator (444). The taxa
      with the most widespread distribution were Ae. aegypti and Toxorhynchites spp,
      followed by Ae. albopictus and Cx. quinquefasciatus. CONCLUSION: Bromeliads in
      urban parks are refuges for populations of native species of Culicidae and
      breeding sites for exotic species that are generally of epidemiological interest.
      Hence, administrators and surveillance and mosquito-control agencies must
      constantly monitor these microenvironments as the presence of these species
      endangers the health of park users and employees as well as people living near
      the parks.

PMID- 27047979
TI  - Respiratory Muscle Paralysis Associated With Colistin, Polymyxin B, and Muscle
      Relaxants Drugs: A Case Report.
AB  - Polymyxins B and E (colistin) exert a bactericidal effect on the gram-negative
      bacterial cell wall, causing permeability changes in the cytoplasmic membrane,
      leading to cell death. Their use was substantially decreased in clinical practice
      from the 1970s to 2000s due to their significant nephrotoxicity and neurotoxicity
      compared to the newly introduced antibiotics. The increasing prevalence of
      multidrug-resistant gram-negative bacteria infections in this century has led to
      an upsurge in the use of these "older" drugs. Respiratory paralysis caused by
      neuromuscular blockage associated with the use of polymyxin B and E was reported
      mostly in literature published in the 1960s to 1970s with a few reports after
      2000. In addition, such a reaction might be enhanced by the presence of other
      classes of drugs. We report a case of polymyxin B and E-induced apnea in a
      patient receiving "muscle relaxants." 

PMID- 27047980
TI  - Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC
      Disease.
AB  - A 70-year-old African American female with a past medical history significant for
      chronic bilateral shoulder pain and reported sickle cell trait presented with
      acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days
      after admission, Hematology was consulted for severely worsening microcytic
      anemia and thrombocytopenia. Examination of the patient's peripheral blood smear
      from admission revealed no cell sickling, spherocytes, or schistocytes. Some
      targeting was noted. A Coombs test was negative. The patient was eventually
      transferred to the medical intensive care unit in respiratory distress.
      Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A
      diagnosis of acute splenic sequestration crisis complicated by acute chest
      syndrome was crystallized, and red blood cell exchange transfusion was performed.
      Further research is necessary to fully elucidate the pathophysiology behind acute
      splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC
      disease patients should be better defined. 

PMID- 27047981
TI  - Longitudinal development of speech motor control: Motor and linguistic factors.

PMID- 27047982
TI  - Clinical Outcomes of High Tibial Osteotomy for Knee Instability: A Systematic
      Review.
AB  - BACKGROUND: In recent years there has been an increasing interest in high tibial
      osteotomy (HTO) to treat patients with chronic knee instability due to
      posterolateral corner (PLC), posterior cruciate ligament (PCL), and anterior
      cruciate ligament (ACL) insufficiencies with concurrent malalignment in the
      coronal and/or sagittal plane. PURPOSE: To perform a systematic review of the use
      of HTO for the treatment of knee ligament instability with concurrent
      malalignment. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A
      systematic review of the literature was conducted for the treatment of combined
      knee ligament instability and malalignment with HTO using the Cochrane Central
      Register of Controlled Trials, PubMed, and MEDLINE (1980 to present); the queries
      were performed in July 2015. Terms searched included the following: high or
      proximal tibial osteotomy, unstable, instability, laxity, subluxation, tibial
      slope, and malalignment, in the knee joint. Inclusion criteria were as follows:
      HTO to treat instability of the knee joint in the sagittal and/or coronal plane,
      minimum 2-year follow-up with reported outcomes measures, English language, and
      human studies. Animal, basic science, and cadaveric studies were excluded as well
      as editorials, reviews, expert opinions, surveys, special topics, letters to the
      editor, and correspondence. RESULTS: The search resulted in 460 studies. After
      applying exclusion criteria and removing duplicates, 13 studies were considered.
      Of the studies reviewed, knee ligament pathologies, previous surgeries, and
      measurement of knee stability were heterogeneous. However, all studies reported
      an improvement in knee stability after HTO. Most studies reported improvement in
      outcome scores. However, other studies did not provide preoperative scores for
      comparison. Reported complication rates ranged from 0% to 47%. CONCLUSION:
      Although HTO has been highly advocated and used in treating patients with
      ligamentous knee instability, there remains a paucity of high-quality studies.
      Included studies report improvement of instability as well as relatively high
      patient satisfaction and rate of return to sports. The heterogeneity of the
      pathology treated, follow-up time, and outcome measures limit comparison between
      studies.

PMID- 27047984
TI  - The Incidence of Surgery in Osteochondritis Dissecans in Children and
      Adolescents.
AB  - BACKGROUND: The frequency of osteochondritis dissecans (OCD), a disorder of the
      subchondral bone and articular cartilage, is not well described. PURPOSE: To
      assess the frequency of pediatric OCD lesions that progress to surgery based on
      sex, joint involvement, and age. STUDY DESIGN: Descriptive epidemiology study.
      METHODS: A retrospective chart review (2007-2011) was performed on OCD. Inclusion
      criteria included OCD of any joint and patients aged 2 to 19 years. Exclusion
      criteria included traumatic osteochondral fractures or coexistence of non-OCD
      intra-articular lesions. Differences in progression toward surgery were compared
      between age groups, sex, and joint location. Logistical regression analysis was
      performed by sex, age, and ethnicity. RESULTS: Overall, 317 patients with a total
      of 334 OCD lesions were found. The majority of lesions (61.7%) were in the knee,
      with ankle, elbow, shoulder, and foot lesions representing 25.4%, 12.0%, 0.6%,
      and 0.3% of all lesions, respectively. The majority of joints needing surgery
      were in the knee (58.5%), with ankle and elbow lesions representing 22.9% and
      18.6% of surgeries performed, respectively. The percentage of all OCD lesions
      progressing to surgery was 35.3%; surgical progression for knee, ankle, and elbow
      joints was 33.5%, 31.8%, and 55.0%, respectively. Logistic regression analysis
      found no statistically significant different risk of progressing to surgery for
      OCD of the knee, elbow, and ankle between sexes. Patients aged 12 to 19 years had
      a 7.4-times greater risk of progression to surgery for knee OCD lesions than 6-
      to 11-year-olds. Patients aged 12 to 19 years were 8.2 times more likely to
      progress to surgery for all OCD lesions than patients aged 6 to 11 years.
      Progression to surgery of ankle OCD did not significantly differ based on
      location. Three of 4 trochlear lesions progressed to surgery, along with 1 of 1
      tibial, 1 of 3 patellar, 40.3% of lateral femoral condylar, and 28.2% of medial
      femoral condylar lesions. CONCLUSION: In this large cohort study of pediatric OCD
      patients, 35% progressed to surgery. Progression to surgery did not differ
      significantly between sexes with OCD of any joint. Progression to surgery for OCD
      of the knee, elbow, and ankle strongly correlated with patient age at the time of
      diagnosis. CLINICAL RELEVANCE: The knowledge of likelihood of progression to
      surgery of OCD by location, sex, and age is useful in counseling patients and in
      planning treatment. This study confirms a worse prognosis in the nonoperative
      treatment of older patients with OCD.

PMID- 27047985
TI  - The Impact of Infectious Disease Specialist Consultation for Staphylococcus
      aureus Bloodstream Infections: A Systematic Review.
AB  - Staphylococcus aureus is a common cause of severe bloodstream infection. We
      performed a systematic review to assess whether consultation with infectious
      disease specialists decreased all-cause mortality or rate of complications of S
      aureus bloodstream infections. The review also assessed parameters associated
      with the quality of management of the infection. We searched for eligible studies
      in PubMed, Embase, Scopus, and clinical trials.gov as well as the references of
      included studies. We identified 22 observational studies and 1 study protocol for
      a randomized trial. A meta-analysis was not performed because of the high risk of
      bias in the included studies. The outcomes are reported in a narrative review.
      Most included studies reported survival benefit, in the adjusted analysis.
      Recommended management strategies were carried out significantly more often among
      patients seen by an infectious disease specialist. Trials, such as cluster
      randomized controlled trials, can more validly assess the studies at low risk of
      bias. 

PMID- 27047983
TI  - A Systematic Summary of Systematic Reviews on the Topic of the Anterior Cruciate
      Ligament.
AB  - BACKGROUND: There has been a substantial increase in the amount of systematic
      reviews and meta-analyses published on the anterior cruciate ligament (ACL).
      PURPOSE: To quantify the number of systematic reviews and meta-analyses published
      on the ACL in the past decade and to provide an overall summary of this
      literature. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A
      systematic review of all ACL-related systematic reviews and meta-analyses
      published between January 2004 and September 2014 was performed using PubMed,
      MEDLINE, and the Cochrane Database. Narrative reviews and non-English articles
      were excluded. RESULTS: A total of 1031 articles were found, of which 240 met the
      inclusion criteria. Included articles were summarized and divided into 17 topics:
      anatomy, epidemiology, prevention, associated injuries, diagnosis, operative
      versus nonoperative management, graft choice, surgical technique, fixation
      methods, computer-assisted surgery, platelet-rich plasma, rehabilitation, return
      to play, outcomes assessment, arthritis, complications, and miscellaneous.
      CONCLUSION: A summary of systematic reviews on the ACL can supply the surgeon
      with a single source for the most up-to-date synthesis of the literature.

PMID- 27047986
TI  - Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus
      Clinics in Zambia and Mozambique.
AB  - Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV)
      infection in sub-Saharan Africa. Among 1812 individuals infected with human
      immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban
      Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV
      replication. 

PMID- 27047987
TI  - Tobacco Smoking Is Not Associated With Accelerated Liver Disease in Human
      Immunodeficiency Virus-Hepatitis C Coinfection: A Longitudinal Cohort Analysis.
AB  - Background.  Tobacco smoking has been shown to be an independent risk factor for
      liver fibrosis in hepatitis C virus (HCV) infection in some cross-sectional
      studies. No longitudinal study has confirmed this relationship, and the effect of
      tobacco exposure on liver fibrosis in human immunodeficiency virus (HIV)-HCV
      coinfected individuals is unknown. Methods.  The study population consisted of
      participants from the Canadian Co-infection Cohort study (CTN 222), a multicenter
      longitudinal study of HIV-HCV coinfected individuals from 2003 to 2014. Data were
      analyzed for all participants who did not have significant fibrosis or end-stage
      liver disease (ESLD) at baseline. The association between time-updated tobacco
      exposure (ever vs nonsmokers and pack-years) and progression to significant liver
      fibrosis (defined as an aspartate-to-platelet ratio index [APRI] >=1.5) or ESLD
      was assessed by pooled logistic regression. Results.  Of 1072 participants
      included in the study, 978 (91%) had ever smoked, 817 (76%) were current smokers,
      and 161 (15%) were previous smokers. Tobacco exposure was not associated with
      accelerated progression to significant liver fibrosis nor with ESLD when
      comparing ever vs never smokers (odds ratio [OR] = 1.06, 95% confidence interval
      [CI], 0.43-1.69 and OR = 1.20, 95% CI, 0.21-2.18, respectively) or increases in
      pack-years smoked (OR = 1.05, 95% CI, 0.97-1.14 and OR = 0.94, 95% CI, 0.83-1.05,
      respectively). Both time-updated alcohol use in the previous 6 months and
      presence of detectable HCV ribonucleic acid were associated with APRI score
      >=1.5. Conclusions.  Tobacco exposure does not appear to be associated with
      accelerated progression of liver disease in this prospective study of HIV-HCV
      coinfected individuals. 

PMID- 27047988
TI  - Data on comparison between FLEC and CLIMPAQ methods used for fast sorption
      measurements of VOCs on building materials.
AB  - A test emission chamber called CLIMPAQ has been coupled to a chromatography
      analyzer GC to measure volatile organic compounds (VOC) concentration during a
      sorption experiments (Fast sorption measurements of VOCs on building materials:
      Part 2 - Comparison between FLEC and CLIMPAQ methods, (Rizk et al., In press)
      [1]). The equations used to calculate the mass transfer coefficient and the
      thickness of the boundary layer developed on the surface of a material are
      presented. In addition, the experimental profiles obtained using the CLIMPAQ
      chamber is also presented in the presence and the absence of a building material.
      Finally, the impact of chamber size on the obtained concentration profile using
      different chambers is shown using 3 types of chambers having different volumes, 1
      m(3), 30 m(3) and a micro chamber of 40 mL. 

PMID- 27047989
TI  - Intrinsic Gastrointestinal Macrophages: Their Phenotype and Role in
      Gastrointestinal Motility.
AB  - There is an increasing awareness of the role of macrophages in the regulation and
      maintenance of gastrointestinal function in health and disease. This work has
      proceeded in the context of an increased understanding of the complex phenotypic
      variation in macrophages throughout the body and has revealed previously un
      identified roles for macrophages in diseases like gastroparesis, post-operative
      ileus and inflammatory bowel disease. Opportunities for exploiting the phenotypic
      modulation of tissue resident macrophages have been identified as possible
      therapies for some of these diseases. In addition, macrophages are an established
      component of the innate immune system that can respond to variations and changes
      in the intestinal microbiome and potentially mediate part of the impact of the
      microbiota on intestinal health. We reviewed the latest work on novel concepts in
      defining macrophage phenotype, discuss possible mechanisms of action for tissue
      resident macrophages in the gut, address the significance of microbiome effects
      on macrophage phenotype and review the known and possible roles of macrophages in
      motility disorders of the gastrointestinal tract.

PMID- 27047990
TI  - A Genetics-based Biomarker Risk Algorithm for Predicting Risk of Alzheimer's
      Disease.
AB  - BACKGROUND: A straightforward, reproducible blood-based test that predicts age
      dependent risk of Alzheimer's disease (AD) could be used as an enrichment tool
      for clinical development of therapies. This study evaluated the prognostic
      performance of a genetics-based biomarker risk algorithm (GBRA) established on a
      combination of Apolipoprotein E (APOE)/Translocase of outer mitochondrial
      membrane 40 homolog (TOMM40) genotypes and age, then compare it to cerebrospinal
      fluid (CSF) biomarkers, neuroimaging and neurocognitive tests using data from two
      independent AD cohorts. METHODS: The GBRA was developed using data from the
      prospective Bryan-ADRC study (n=407; 86 conversion events (mild cognitive
      impairment (MCI) or late onset Alzheimer's disease (LOAD)). The performance of
      the algorithm was tested using data from the ADNI study (n=660; 457 individuals
      categorized as MCI or LOAD). RESULTS: The positive predictive values (PPV) and
      negative predictive values (NPV) of the GBRA are in the range of 70-80%. The
      relatively high odds ratio (approximately 3-5) and significant net
      reclassification index (NRI) scores comparing the GBRA to a version based on APOE
      and age alone support the value of the GBRA in risk prediction for MCI due to
      LOAD. Performance of the GBRA compares favorably with CSF and imaging (fMRI)
      biomarkers. In addition, the GBRA "high" and "low" AD-risk categorizations
      correlated well with pathological CSF biomarker levels, PET amyloid burden and
      neurocognitive scores. CONCLUSIONS: Unlike dynamic markers (i.e., imaging,
      protein or lipid markers) that may be influenced by factors unrelated to disease,
      genomic DNA is easily collected, stable, and the technical methods for
      measurement are robust, inexpensive, and widely available. The performance
      characteristics of the GBRA support its use as a pharmacogenetic enrichment tool
      for LOAD delay of onset clinical trials, and merits further evaluation for its
      clinical utility in evaluating therapeutic efficacy.

PMID- 27047991
TI  - Cross-Disciplinary Network Comparison: Matchmaking Between Hairballs.
AB  - Biological systems are complex. In particular, the interactions between molecular
      components often form dense networks that, more often than not, are criticized
      for being inscrutable 'hairballs'. We argue that one way of untangling these
      hairballs is through cross-disciplinary network comparison-leveraging advances in
      other disciplines to obtain new biological insights. In some cases, such
      comparisons enable the direct transfer of mathematical formalism between
      disciplines, precisely describing the abstract associations between entities and
      allowing us to apply a variety of sophisticated formalisms to biology. In cases
      where the detailed structure of the network does not permit the transfer of
      complete formalisms between disciplines, comparison of mechanistic interactions
      in systems for which we have significant day-to-day experience can provide
      analogies for interpreting relatively more abstruse biological networks. Here, we
      illustrate how these comparisons benefit the field with a few specific examples
      related to network growth, organizational hierarchies, and the evolution of
      adaptive systems.

PMID- 27047992
TI  - Rapid identification of ubiquitination and SUMOylation target sites by
      microfluidic peptide array.
AB  - SUMOylation and ubiquitination are two essential post translational modifications
      (PTMs) involved in the regulation of important biological processes in eukaryotic
      cells. Identification of ubiquitin (Ub) and small ubiquitin-related modifier
      (SUMO)-conjugated lysine residues in proteins is critical for understanding the
      role of ubiquitination and SUMOylation, but remains experimentally challenging.
      We have developed a powerful in vitro Ub/SUMO assay using a novel high density
      peptide array incorporated within a microfluidic device that allows rapid
      identification of ubiquitination and SUMOylation sites on target proteins. We
      performed the assay with a panel of human proteins and a microbial effector with
      known target sites for Ub or SUMO modifications, and determined that 80% of these
      proteins were modified by Ub or specific SUMO isoforms at the sites previously
      determined using conventional methods. Our results confirm the specificity for
      both SUMO isoform and individual target proteins at the peptide level. In
      summary, this microfluidic high density peptide array approach is a rapid
      screening assay to determine sites of Ub and SUMO modification of target
      substrates, which will provide new insights into the composition, selectivity and
      specificity of these PTM target sites.

PMID- 27047993
TI  - Chloroquine increases phosphorylation of AMPK and Akt in myotubes.
AB  - AIMS: There are reports that ataxia telangiectasia mutated (ATM) can activate the
      AMP-activated protein kinase (AMPK) and also Akt, two kinases that play integral
      parts in cardioprotection and metabolic function. We hypothesized that
      chloroquine and resveratrol, both known ATM activators, would also activate AMPK
      and Akt. MAIN METHODS: Phosphorylation of AMPK and Akt was assessed after C2C12
      myotubes were exposed to chloroquine or resveratrol. Additional experiments were
      done in cells expressing shRNA against ATM or in the presence of the ATM
      inhibitor KU55933. The effects of chloroquine on intracellular calcium were
      assessed with the fluorescent probe Calcium Green-1 AM. KEY FINDINGS: 0.5 mM
      chloroquine increased AMPK phosphorylation by nearly 4-fold (P<0.05), and 0.25 mM
      chloroquine roughly doubled Akt phosphorylation (P<0.05). Chloroquine also
      increased autophosphorylation of ATM by ~50% (P<0.05). Resveratrol (0.15 mM)
      increased AMPK phosphorylation about three-fold (P<0.05) but in contrast to
      chloroquine sharply decreased Akt phosphorylation. Chloroquine increased AMPK and
      Akt phosphorylation in myotubes expressing shRNA against ATM that reduced ATM
      protein levels by about 90%. Likewise, chloroquine-stimulated phosphorylation of
      AMPK and Akt and resveratrol-stimulated phosphorylation of AMPK were not altered
      by inhibition of ATM. Chloroquine decreased intracellular calcium by >50%
      concomitant with a decrease in glucose transport. SIGNIFICANCE: These ATM
      independent effects of chloroquine on AMPK and Akt and the additional effect to
      decrease intracellular calcium are likely to partially underlie the positive
      metabolic effects of chloroquine that have been reported in the literature.

PMID- 27047995
TI  - Heteronuclear DNP of protons and deuterons with TEMPOL.
AB  - Dynamic nuclear polarization (DNP) experiments on samples with several types of
      magnetic nuclei sometimes exhibit "cross-talk" between the nuclei, such as
      different nuclei having DNP spectra with similar shapes and enhancements. In this
      work we demonstrate that while at 20 K the DNP spectra of (1)H and (2)H nuclei,
      in a sample composed of 50% v/v (1)H2O/DMSO-d6 and containing 40 mM TEMPOL, are
      different and can be analyzed using the indirect cross effect (iCE) model, at 6 K
      the DNP spectra of both (1)H and (2)H nuclei become identical. In addition we
      experimentally demonstrate that there exists an efficient polarization exchange
      between the two nuclear pools at this temperature. Both of these results are
      hallmark predictions of the thermal mixing (TM) formalism. However, the origin of
      these observations cannot, in our case, be explained using the standard TM
      formalism, as in our sample the electron reservoir cannot be described by a
      single non-Zeeman spin temperature, which is a prerequisite of TM. This
      conclusion follows from the analysis of the electron electron double resonance
      (ELDOR) experiments on our sample and is similar to the previously published
      results. Consequently, another mechanism must be used in order to explain these
      "cross-talk" effects. The heteronuclear cross effect (hnCE) DNP mechanism,
      previously introduced based on the simulations of the spin evolution in small
      model systems, results in "cross-talk" effects between two types of nuclei that
      are similar to the experimental ones seen in this work. In particular we show
      that the hnCE mechanism exhibits polarization transfer between the nuclei and
      that there exists a clear relationship between the steady state polarizations of
      the two types of nuclei which may, in the future, be correlated with the
      phenomenon observed in the two types of bulk nuclear signals in samples during
      DNP experiments. It is suggested that the hnCE electrons are a possible source
      for the process that equalizes the bulk enhancements of the (1)H and (2)H nuclei
      and are responsible for the observed cross-talk effects. 

PMID- 27047994
TI  - Individualized Prediction and Clinical Staging of Bipolar Disorders using
      Neuroanatomical Biomarkers.
AB  - BACKGROUND: Neuroanatomical abnormalities in Bipolar disorder (BD) have
      previously been reported. However, the utility of these abnormalities in
      distinguishing individual BD patients from Healthy controls and stratify patients
      based on overall illness burden has not been investigated in a large cohort.
      METHODS: In this study, we examined whether structural neuroimaging scans coupled
      with a machine learning algorithm are able to distinguish individual BD patients
      from Healthy controls in a large cohort of 256 subjects. Additionally, we
      investigated the relationship between machine learning predicted probability
      scores and subjects' clinical characteristics such as illness duration and
      clinical stages. Neuroimaging scans were acquired from 128 BD patients and 128
      Healthy controls. Gray and white matter density maps were obtained and used to
      'train' a relevance vector machine (RVM) learning algorithm which was used to
      distinguish individual patients from Healthy controls. RESULTS: The RVM algorithm
      distinguished patients from Healthy controls with 70.3 % accuracy (74.2 %
      specificity, 66.4 % sensitivity, chi-square p<0.005) using white matter density
      data and 64.9 % accuracy (71.1 % specificity, 58.6 % sensitivity, chi-square
      p<0.005) with gray matter density. Multiple brain regions - largely covering the
      fronto - limbic system were identified as 'most relevant' in distinguishing both
      groups. Patients identified by the algorithm with high certainty (a high
      probability score) - belonged to a subgroup with more than ten total lifetime
      manic episodes including hospitalizations (late stage). CONCLUSIONS: These
      results indicate the presence of widespread structural brain abnormalities in BD
      which are associated with higher illness burden - which points to
      neuroprogression.

PMID- 27047996
TI  - Bioresorbable Scaffolds to Treat Spontaneous Coronary Artery Dissection.

PMID- 27047997
TI  - Critical care nursing: Embedded complex systems.
AB  - Variability in parameters such as heart rate, respiratory rate and blood pressure
      defines healthy physiology and the ability of the person to adequately respond to
      stressors. Critically ill patients have lost this variability and require highly
      specialized nursing care to support life and monitor changes in condition. The
      critical care environment is a dynamic system through which information flows.
      The critical care unit is typically designed as a tree structure with generally
      one attending physician and multiple nurses and allied health care professionals.
      Information flow through the system allows for identification of deteriorating
      patient status and timely interventionfor rescue from further deleterious
      effects. Nurses provide the majority of direct patient care in the critical care
      setting in 2:1, 1:1 or 1:2 nurse-to-patient ratios. The bedside nurse-critically
      ill patient relationship represents the primary, real-time feedback loop of
      information exchange, monitoring and treatment. Variables that enhance
      information flow through this loop and support timely nursing intervention can
      improve patient outcomes, while barriers can lead to errors and adverse events.
      Examining patient information flow in the critical care environment from a
      dynamic systems perspective provides insights into how nurses deliver effective
      patient care and prevent adverse events.

PMID- 27047998
TI  - Continuous Renal Replacement Therapy (CRRT) practices in Canadian hospitals:
      Where are we now?
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication in critically ill
      patients. Renal replacement therapy is prescribed for as many as 70% of
      critically ill patients in AKI and may be provided in the form of intermittent or
      continuous dialysis including intermittent hemodialysis, sustained low-efficiency
      dialysis, and continuous renal replacement therapy (CR RT). CRRT is commonly used
      for unstable critically ill patients, as it involves a slow continuous process.
      The nursing work involved with CR RT is highly complex and the learning
      requirements are challenging; therefore, it is important to identify nursing
      practices. PURPOSE: A national survey was conducted to gain insight into CRRT
      nursing practices. METHODS: T he design for this study was descriptive using a
      survey The target population for this survey was ICU nurse educators at Canadian
      teaching and community hospitals. Topics in the survey included staff education,
      CRRT ordering and initiation practices, vascular access, filters and filter life,
      fluids used, anticoagulation methods, adverse events, and greatest concerns.
      FINDINGS: One hundred and twenty-nine surveys were sent out and 73 were returned
      for a response rate of 57%. Thirty-six hospitals used CRRT and of these, 73% had
      used CR RT for more than eight years. The findings revealed that educators
      identified achieving and maintaining competence as their greatest concern related
      to CRRT practices. CONCLUSION: The fndings of this research revealed that
      consistent training programs were not the norm. The complexity of caring for
      patients on CRRT requires consideration of when to introduce to staff the
      technology and care of patients on CRRT and how to sustain their competence.

PMID- 27047999
TI  - An integrative review of in situ simulation training: Implications for critical
      care nurses.
AB  - BACKGROUND: In situ simulation (ISS) is an emerging teaching strategy aimed to
      improve professionals' competencies and collaborative practice to increase
      patient safety The impact of ISS is still to be demonstrated before expanding the
      use of this method in our critical care settings. PURPOSE: The objective of this
      paper is to explore the literature regarding ISS training and present advantages
      and challenges. DESIGN AND METHOD: An integrative review was conducted, based on
      the preferred reporting items for systematic reviews and meta-analyses (PRISMA)
      statement. Online databases MEDLINE and CINAHL were searched. The main keywords
      used were "in situ simulation", "communication" and "interdisciplinary". We
      excluded studies conducted outside of the hospital or the clinic, single case
      studies and framework analyses. FINDINGS: Twenty-eight articles were reviewed.
      Studies were mainly descriptive and exploratory. They underlined the advantages
      and challenges of the ISS training regarding safety, as well as the perspectives
      of patients, families, health care providers and administrators. CONCLUSION AND
      NURSING IMPLICATIONS: Although ISS is a promising educational strategy to
      increase patient safety, there is still a need for higher evidence level research
      to support its efficacy to improve competencies. With regard to patient safety
      improvement, ISS-based training offers opportunities to identify hazards and
      deficiencies of clinical systems and the provider team. Experimental studies are
      necessary to increase evidence about the impact of ISS training.

PMID- 27048000
TI  - There's a New "Bug" in Town: What You Need to Know About the Zika Virus.

PMID- 27048001
TI  - Advocacy to Reduce the Stigma: Intervention Project for Nurses.

PMID- 27048002
TI  - Dr. Gary Roberts, President-Elect of the American Dental Association.

PMID- 27048003
TI  - Life is a gift, and it offers us the privilege, opportunity, and responsibility
      to give something back by becoming more.

PMID- 27048004
TI  - Six Smart Financial Decisions that Don't Follow the Crowd.

PMID- 27048005
TI  - A Culture of Courage and Resilience: Lessons from survivors of the flood who
      found ways to thrive.

PMID- 27048006
TI  - What Social Media Platforms Should Be Used By A Dental Practice?

PMID- 27048007
TI  - Please Take My Picture.

PMID- 27048008
TI  - Comment on "vaginal bilateral cervical lips suture in combination with
      intrauterine Foley catheter to arrest postpartum hemorrhage".

PMID- 27048009
TI  - Reply by Qiao et al.

PMID- 27048010
TI  - Pre-eclampsia and the vascular endothelial growth factor: a new aspect.
AB  - Pre-eclampsia (PE) is a multi-system disorder of human gestation characterized by
      hypertension, proteinuria, and edema, which resolves with placental delivery.
      This disease affects 3-14% of all pregnancies worldwide and 5-8% in the USA.
      Furthermore PE remains one of the leading causes of maternal and neonatal
      mortality and morbidity worldwide. One of the most important goals in obstetrics
      is the early identification of the patient with an increased risk for PE. This
      paper unifies the essential and validated findings of past and current scientific
      investigation which encompass the relationship between PE and the vascular
      endothelial growth factor (VEGF). VEGF and its receptors have acquired great
      interest due to their vital role in neovascularization (vasculogenesis and
      angiogenesis) in a variety of physical and pathological processes such as the
      female reproductive cycle, PE, and tumorigenesis. VEGF is secreted in response to
      tissue hypoxia and endothelial cell damage. Alterations in the circulating levels
      of this factor may therefore identify those pregnancies with a high possibility
      of developing PE. This review will summarize the present authors' current
      understanding of the role of circulating VEGF in the pathogenesis, clinical
      diagnosis, and prediction of PE.

PMID- 27048011
TI  - Intravenous intralipid therapy is not beneficial in having a live delivery in
      women aged 40-42 years with a previous history of miscarriage or failure to
      conceive despite embryo transfer undergoing in vitro fertilization-embryo
      transfer.
AB  - PURPOSE: To evaluate the efficacy of intralipid intravenous infusion in achieving
      a live pregnancy following IVF--embryo transfer in women of advanced reproductive
      age (40-42 years). MATERIALS AND METHODS: A matched control was performed. Women
      aged 40-42 with a previous history of miscarriage or who failed to conceive
      despite previous embryo transfer who entered an IVF program were offered
      intravenous intralipid therapy (four ml of 20% liposyn II in 100 ml normal saline
      over one hour) during the mid-follicular phase. Clinical pregnancy rates (eight
      weeks with viable gestation) and live delivered pregnancy rates were then
      determined and compared. RESULTS: The results were evaluated after ten matched
      cycles. There were no clinical pregnancies in those receiving intralipid vs. a
      40% clinical and a 30% live delivered pregnancy rate in the untreated controls (p
      = 0.087, Fisher's exact test). The study was terminated because of these
      preliminary data. CONCLUSIONS: In the test tube, adding intralipid to natural
      killer cells can inhibit their cytolytic action. However, the use of intravenous
      intralipid to suppress natural killer cell activity does not seem to improve the
      chance of a live delivery in women aged 40-42 years with a previous history of
      miscarriage. In fact this therapy may actually be detrimental in this age group.
      Since efficacy of this therapy was not found in a group of advanced reproductive
      age, it is not clear why this should be effective for a younger population. A
      controlled study for the younger group is needed. Perhaps such a study could be
      limited to only those with miscarriage rather than also concluding failure to
      conceive despite embryo transfer. Intralipid failed to improve live delivered
      pregnancy rates in women with prior miscarriage or previous failure with embryo
      transfer.

PMID- 27048012
TI  - HDLive ultrasound images of ovarian dermoid cysts: diagnostic accuracy.
AB  - OBJECTIVE: To demonstrate that the use of 3D/4D HDLive increases the image
      quality in the diagnosis of benign cystic ovarian teratomas. MATERIALS AND
      METHODS: 3D/HDLive ultrasound (US) was used in 31 cases of suspected ovarian
      cystic teratoma using vaginal 2D US. The following pathognomonic images of mature
      cystic teratomas were considered for diagnosis: 1) a cystic, unilocular lesion
      with a densely echogenic tubercle (Rokitansky nodule); 2) a diffuse or partially
      echogenic mass usually demonstrating sound attenuation; 3) fluid-fluid/fat-fluid
      levels; 4) dermoid mesh with hyperechogenic calcifications indicating the
      presence of bone, teeth, or other ectodermally-derived structure; 5) multiple
      mobile spherical structures (fat globules). RESULTS: Dermoids present a wide
      spectrum of images depending on the predominant tissue type. In the vast majority
      of cases there are dense echogenic structures that correspond to complex masses
      of fatty tissue, sebum, hair, epithelial remnants, along with cartilage or bone.
      If we catalogue all the images together, the pathognomonic of dermoid are: 1)
      cystic or solid cystic lesions with a Rokitansky nodule, with bone, teeth or
      cartilage (six cases, 22.2%); 2) a solid mass with or without attenuation that
      corresponds with pure sebum (five cases, 18.5%); 3) a diffuse mass with fine
      bands that correspond with hair inside sebum (four cases, 12.9%) and that may
      form meshes or plugs corresponding with a mixture of fat, sebum, and hair (three
      cases, 11.5%). CONCLUSIONS: HDLive U.S. provides some images of exceptional
      quality that enhance the definition of the structures of these tumors (fat, hair,
      cartilage, bone, etc.) compared to 2D/3D/4D.

PMID- 27048013
TI  - The effects of melatonin on endometriotic lesions induced by implanting human
      endometriotic cells in the first SCID-mouse endometriosis-model developed in
      Turkey.
AB  - OBJECTIVE: To evaluate the effects of melatonin on endometriotic lesions induced
      by implanting human endometriotic cells in SCID mice. MATERIALS AND METHODS:
      Prospective, randomized, controlled, experimental study. Experimental Research
      Center of Yeditepe University (YUDETAM). Thirty female, non-pregnant, nulligravid
      severe combined immunodeficient (SCID) mice. Endometriotic cells collected from
      patients with endometriosis were implanted subcutaneously in 30 SCID mice. These
      mice were randomized into two study groups: in the first group, mice were
      administered melatonin (20 mg/kg/day) following induction of endometriosis for
      four weeks; in the second group, nothing was administered. All the mice were
      given a high dose of exogenous estradiol (50 ug/kg/d, twice weekly). Four weeks
      after inoculation, necropsies were performed and endometriotic lesions were
      collected. All the lesions were evaluated histopathologically and the levels of
      SOD and MDA were assessed in the lesions. RESULTS: Successful implantation was
      observed in the 28 mice that survived. Mean MDA level was 5.0 +/- 1.7 and 8.8 +/-
      2.6 in the melatonin and control groups, respectively (p = 0.01); mean SOD level
      was 1.1 +/- 0.1 and 1.0 +/- 0.1 in the melatonin and control groups, respectively
      (p = 0.49). Mean histopathological score was lower in the melatonin group (p =
      0.04). CONCLUSIONS: Melatonin was effective in the treatment of experimental
      endometriosis induced in SCID mice.

PMID- 27048014
TI  - Laparoscopic surgery improves pregnancy outcomes in women with suspected
      endometriosis with or without pathological confirmation.
AB  - PURPOSE OF THE INVESTIGATION: To verify whether histologic confirmation of
      endometriosis impacts fertility outcomes. MATERIALS AND METHODS: Women with
      unexplained infertility (UI) underwent laparoscopic excision or ablation with CO2
      laser or electrocautery of all suspected endometriotic lesions, followed by
      clinical treatment between January 2007 and December 2013; pregnancy (> 12 weeks)
      within 12 months of monitored cycles was the main outcome measured. RESULTS:
      Women with histological confirmation (n = 74) did not differ from those not
      confirmed (n = 29) with age, body mass index, gravidity, parity, ovulation
      induction protocol, and past duration of infertility. Pregnancy outcome was
      similar in both groups (39/74 vs. 15/29-p = 0.9--Chi-square) and there was no
      statistical difference in time to conceive/deliver (p = 0.7) between groups.
      CONCLUSIONS: There is no difference in fertility outcomes in women with UI,
      whether or not suspected endometriosis is confirmed pathologically.

PMID- 27048015
TI  - Uterine contractility as a cause of amniotic band syndrome.
AB  - OBJECTIVE: The objective of this study was to determine whether puncturing the
      uterine wall and the amnion causes uterine contractions that result in fetal
      abnormalities. MATERIALS AND METHODS: An experimental study was performed using
      four groups of three female rabbits. Group A received a puncture of the amniotic
      membranes of one of the uteri on day 15 of gestation followed by group B on day
      16, group C on day 17, and group D on day 18. The duration and force of
      contractions and fetal abnormalities were determined. RESULTS: There were
      immediate contractions after the puncture, which lasted 20 to 132 seconds with
      forces that ranged from 309 to 4,411 mg. All of the experimental fetuses
      exhibited anomalies of the head and extremities, exencephaly, cleft palates, and
      an absence of eye-lids. CONCLUSION: Injury to the uterine wall and the aniion can
      immediately cause uterine contractions, which are associated with different types
      of fetal abnormalities.

PMID- 27048016
TI  - Predictive value of biochemical marker ADAM-12 at first trimester of pregnancy
      for hypertension and intrauterine growth restriction.
AB  - PURPOSE: Delineate whereas ADAM-12 levels at first trimester of pregnancy may be
      used as a marker for hypertension-preeclampsia (PE) and intrauterine growth
      restriction (IUGR). MATERIALS AND METHODS: The present is a case control study.
      Serum ADAM-12 of women presenting for routine assessment of risk for chromosomal
      abnormalities at 11+0 to 13+6 weeks of gestation was measured. The study group
      comprised of 98 pregnancies that subsequently developed pregnancy-induced
      hypertension (PIH) or PE or small for gestational age fetuses (SGA), and were
      compared to 100 uncomplicated pregnancies. RESULTS: There was no statistically
      significant difference of mean log multiple of the expected median (MoM) of
      ADAM12 between control group and the group that consisted of all women with
      complicated pregnancy (PE, PIH, and SGA). ADAM-12 levels in women who developed
      PE during pregnancy were significantly lower than in womien of control group
      (mean log MoM: 0.109 vs 0.008, p = 0.010). Similarly, ADAM-12 levels in women who
      developed PE and/or PIH were significantly lower than in women of control group
      (mean log MoM: 0.066 vs 0.008, p = 0.015). There was no significant difference of
      ADAM12 levels between controls and pregnancies with SGA fetuses. CONCLUSION:
      Maternal serum levels of ADAM-12 at the first trimester are significantly lower
      in women who later develop PE when compared with women with uncomplicated
      pregnancies.

PMID- 27048017
TI  - Pregnancy after heart surgery--challenges.
AB  - PURPOSE: Advances in cardiac surgery significantly improve life expectancy and
      quality of life of patients with congenital or acquired heart disease. MATERIALS
      AND METHODS: The present study included 146 pregnant women who had antenatal care
      and gave birth at the Institute of Gynecology and Obstetrics in an interval of
      ten years from 1994-2004. Patients were divided in four groups according to the
      type of heart surgery. Group I included four patients with surgically corrected
      coarctation of the aorta. Group II included 27 patients with correction of the
      ostial stenosis. Group III had 68 patients with correction of congenital heart
      diseases, and group IV had 47 patients with artificial heart valves. RESULTS:
      There was 4% of heart failure after delivery. The incidence of hemorrhagic
      complications during pregnancy was 2.7% and 4.1% after delivery. The incidence of
      thromboembolic complications after delivery was 6%. Four newborns died; one of
      hydrocephalus and three of hypoxic ischemic encephalopathy. Two patients died.
      CONCLUSION: Patients with artificial heart valves need an enhanced level of
      medical care during pregnancy and labor.

PMID- 27048018
TI  - Experience of assisted reproductive technology at King Abdulaziz University
      Hospital.
AB  - AIM: To present the authors' experience with assisted reproductive technology
      (ART) at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. MATERIALS
      AND METHODS: Retrospective analysis of data collected from the charts of 264
      women who were undergoing their first cycle of ART between September 2013 and
      March 2014. All the women were treated with gonadotropin-releasing hormone (GnRH)
      antagonist protocol. For all patients, the documented data included age,
      infertility type, cause, and hormone profile. Number of follicles > 10 mm,
      endometrial thickness, number of oocytes retrieved, number of fertilized ova, and
      number of embryos produced, as well as the number transferred, day of transfer,
      cancellation rate, and treatment administered for luteal phase support (oral and
      vaginal progesterone) treatment type, and outcome were recorded. The data was
      analyzed using the Statistical Package for the Social Sciences. RESULTS: The
      authors included women aged 21 to 39 years (mean +/- standard deviation, 32.28 +/
      5.51). Patients suffered from primary infertility in 69.7% of the cases;
      approximately 30% of the women had secondary infertility. Eighty of the 264
      patients (30.3%) conceived; however, only 56 women (21.2%) had a live birth. The
      overall cancellation rate in the patients was 12.1%. The following reasons were
      documented for cases of failure: no oocytes, 16 (6.1%); no sperm, eight (3.0%);
      and no embryo, eight (3.0%). CONCLUSION: The success rate of ART at the present
      institution falls within the range reported in the medical literature. However,
      further studies should be conducted to investigate the course and outcome of ART
      in patients who undergo treatment in this institution.

PMID- 27048019
TI  - Follow-up observational study of "bi-ring method" breast surgery for treating
      hypermastia and mastoptosis.
AB  - PURPOSE: This study investigated the efficacy and patient satisfaction of "bi
      ring method" breast surgery in 46 patients with hypermastia and/or mastoptosis.
      MATERIALS AND METHODS: A questionnaire survey, objective data measurements,
      visual analysis system survey, and various scoring scales were used to
      qualitatively and quantitatively assess the patients' indicators before and after
      surgery. RESULTS: Statistical analysis showed the following: symptoms and signs
      in patients with macromastia improved significantly; all patients' breast shapes
      improved significantly and became more symmetrical and durable; all patients had
      minor hidden scars; the nipples and areolas had good feeling postoperatively, and
      there were relatively few mild complications. CONCLUSIONS: The patients' overall
      satisfaction was high, indicating that the "bi-ring method" of breast plastic
      surgery could not only improve the breast shape and boast concealed scars but
      could significantly improve the patients' signs and symptoms of hypermastia, but
      the nipples and areolas had good postoperative feeling and there were few
      complications. Thus, this is a reasonable surgical approach that is worthy of
      promotion.

PMID- 27048020
TI  - Fetal ventriculomegalies during pregnancy course, outcome, and psychomotor
      development of born children.
AB  - PURPOSE: The objectives of this study were as follows: to present the course and
      outcome of pregnancies complicated with fetal ventriculomegaly, determine the
      association between prenatal ultrasound diagnoses and definitive postnatal
      diagnosis or diagnoses after autopsy and additional analysis, and to monitor the
      psychomotor development of children born with ventriculomegaly. MATERIALS AND
      METHODS: The survey was designed as retrospective study and included 62 pregnant
      women who were attending a regular ultrasound examinations at the Department of
      Gynecology and Obstetrics, Clinical Center of Serbia, or patients who were
      referred from other institutions in Serbia. RESULTS: Ventriculomegalies were
      divided into three groups: mild, moderate, and severe or hydrocephalus. The most
      common were severe ventriculomegalies, with 34 cases (55%). Of all pregnancies
      complicated with ventriculomegalies, 61% were terminated. Among those continued,
      88% had normal psychomotor development. In 97% ultrasonographic diagnosis was
      confirmed. CONCLUSION: Majority of pregnancies complicated with ventriculomegaly
      were continued and most of the children born with anomalies had normal
      psychomotor development.

PMID- 27048021
TI  - Correlation of twisting motion phase and infantile spasms in high risk infants.
AB  - OBJECTIVE: The aim of this study was to investigate the correlation of twisting
      motion phase and infantile spasms in high risk infants. MATERIALS AND METHODS:
      One hundred seventy-eight high-risk newborns experiencing follow-up in the
      rehabilitation phase were selected and full-body motion quality assessment was
      performed in the twisting motion phase. The occurrence of infants with infantile
      spasms after 12 months (corrected age) was statistically analyzed. RESULTS: No
      clear correlation was found between monotonous movement twisting motion phase and
      infantile spasms, and spasm synchronized movement had no definite prediction for
      infantile spasms. The incidence of infant spasm with movement form having spastic
      synchronized characteristics had significant difference compared with monotonous
      systemic movement (p < 0.01). The sensitivity of predictive rate for spasm
      synchronous movement of infantile spasms was 90.9%, the specificity was 96.8%,
      the positive predictive value was 80%, and the negative predictive value was
      98.7%. CONCLUSIONS: Spasm synchronized movement had some predictive value for
      infantile spasms in twisting motion stage. The newborns with this kind of
      movement form should be checked by regularly ambulatory EEG.

PMID- 27048022
TI  - Expression and significance of ERbeta and TrkB in endometriosis.
AB  - OBJECTIVES: To study the potential pathogenesis of endometriosis (EMs) in an area
      of estrogen receptors (ERs) and tyrosine kinase receptor type B (TrkB)
      expressions in tissues from patients with EMs. STUDY DESIGN: The authors examined
      the expressions of ERalpha, ERbeta, TrkB, brain-derived neurotrophic factor
      (BDNF), and SGPL1 in tissues with EMs, using real-time PCR, western blot, and
      immunohistochemistry. RESULTS: ERalpha and SGPL1 were mainly expressed in eutopic
      endometrium than that in ectopic endometrium of patients with ovarian
      endometriosis (p < 0.05), while ERbeta, BDNF, and TrkB were adverse, mainly
      detected in ectopic endometrium of the same patients with EMs (p < 0.01 and p <
      0.05 ) by real-time PCR and western blot. ERbeta, ERalpha, TrkB, and SGPL1
      proteins were mainly expressed in eutopic endometrium of proliferative phase with
      EMs than that in eutopic endometrium of secretory phase (p < 0.05 ). TrkB, BDNF,
      and SGPL1 were not found in endometrium of proliferative or secretory phase in
      control group. CONCLUSIONS: ERbeta expressed in cytoplasm may mediate
      pathogenesis of EMs.

PMID- 27048023
TI  - Histopathology of ipsilateral and contralateral ovaries and plasma interleukin 6
      levels after unilateral ovarian torsion.
AB  - OBJECTIVE: The aim of the present study was to evaluate the time-dependent
      histopathologic changes in both ovaries and to determine the time-dependent
      levels of plasma interleukin 6 (IL-6) after unilateral ovarian torsion. MATERIALS
      AND METHODS: An experimental animal study included 48 female Sprague-Dawley rats
      which were distributed to six groups: control group (Group 1), sham-operated
      control group (Group 2), and four unilateral ovarian torsion groups with torsion
      duration of three, six, 12, and 24 hours (Group 3, 4, 5, and 6, respectively).
      Histopathologic criteria (follicular degeneration, vascular congestion,
      hemorrhage, inflammatory cell infiltration, and total tissue damage score) were
      evaluated in both ovaries, and plasma IL-6 levels were measured. RESULTS: At 24
      hours after torsion began, mean total tissue damage score was similar between
      ovaries that had torsion and contralateral ovaries. Mean plasma IL-6 level did
      not change during the 24 hours after torsion began (p = 0.584). CONCLUSIONS: In
      addition to ovaries that had torsion, histopathologic abnormalities also occurred
      in contralateral ovaries. These results suggest that contralateral ovaries are
      not quiescent after unilateral ovarian torsion. Plasma IL-6 levels did not change
      significantly during the 24 hours after ovarian torsion began, resulting in a
      limitation of its diagnostic use in the early course of the disease.

PMID- 27048024
TI  - The impact of chorionicity and type of conception on maternal-neonatal outcome in
      twin pregnancies.
AB  - PURPOSE OF INVESTIGATION: To evaluate the maternal and neonatal outcomes in twin
      pregnancies according to chorionicity (monochorionic (MC) versus dichorionic (DC)
      and type of conception [spontaneously conceived (SC) versus assisted reproduction
      technology (ART)]. MATERIALS AND METHODS: A retrospective study of 196 twin
      pregnancies admitted to the Department of Gynecology, Obstetrics and Urology of
      the University of Rome Sapienza, from January 2008 to April 2013. RESULTS: There
      were 55 MC and 141 DC twin pregnancies (82 SC and 59 ART). MC twin pregnancies
      had a higher incidence of preterm birth (p < 0.008), twin-twin transfusion
      syndrome (TTTS) (p < 0.021), and intrauterine growth restriction (IUGR) (p <
      0.05). MC pregnancies had lower neonatal birth weight (p < 0.05), and lower Apgar
      score. ART DC pregnancies had a higher incidence of preterm delivery (p < 0.05).
      CONCLUSIONS: MC twin pregnancy is associated with higher risk of adverse maternal
      and perinatal outcomes. In the DC subgroup, ART is associated to a higher
      incidence of preterm delivery.

PMID- 27048025
TI  - Comparison of mechanical artificial shrinkage methods in mouse blastocyst
      vitrification.
AB  - PURPOSE OF INVESTIGATION: This study was designed to determine which mechanical
      artificial shrinkage (AS) method, conducted by puncture, pipetting, or
      aspiration, was effective in increasing the re-expansion rate of mouse
      blastocysts. MATERIALS AND METHODS: In each group, 30 mouse blastocysts were
      used. Before vitrification, the blastocoelic cavity was collapsed by puncture
      with a micro-needle, pipetting with a micro-glass pipette, and direct aspiration
      with an ICSI pipette. After thawing, the re-expansion rate of blastocysts was
      examined for each AS method. Re-expansion rate was checked at three, five, and
      seven hours after thawing. RESULTS: The number of re-expanded mouse blastocysts
      at five hours after thawing was 12 in the puncture with a micro-needle group, 11
      in the pipetting with a micro-glass pipette group, and 24 in the direct
      aspiration with an ICSI pipette group. The cumulative number of re-expanded mouse
      blastocysts at seven hours after thawing was 20 in the puncture with a micro
      needle group, 20 in the pipetting with a micro-glass pipette group, and 28 in the
      direct aspiration with an ICSI pipette group. There were statistically
      significant differences in the cumulative number of re-expanded mouse blastocysts
      between five and seven hours after thawing (p = 0.001 and 0.021, respectively).
      CONCLUSIONS: Direct aspiration with an ICSI pipette resulted in a higher re
      expansion rate than the puncture and pipetting methods. It can be considered that
      the direct aspiration method is more convenient and simpler than the other two
      methods.

PMID- 27048026
TI  - The possible role of serum leptin in preeclampsia.
AB  - BACKGROUND: It is theorized that adipokines play a critical role in the
      pathophysiology of preeclampsia, particularly with their pro-inflammatory and
      inflammatory features. AIM: To investigate serum leptin levels in pregnancies
      complicated with preeclampsia and severe preeclampsia. MATERIALS AND METHODS:
      Maternal serum leptin levels were analyzed by solid phase enzyme amplified
      sensitivity immunoassay (EASIA) method in 23 patients with mild preeclampsia, 29
      patients with severe preeclampsia, and 28 healthy pregnant controls. RESULTS:
      Mean serum leptin levels did not differ statistically between patients with mild
      preeclampsia, severe preeclampsia, and the controls (10.77 ng/ml, 13.40 ng/ml,
      and 8.43 ng/ml, respectively). Also, there was no relationship between serum
      leptin levels and the gestational ages of the participants. DISCUSSION: Serum
      leptin levels are not associated with preeclampsia. Leptin measurements are not
      affected with the gestational age. The role of leptin in the pathophysiology of
      preeclampsia should be evaluated cautiously.

PMID- 27048027
TI  - Effect of pregnancy-specific stress on spontaneous preterm birth among Chinese
      people.
AB  - BACKGROUND: The current evidence implicates that psychosocial stress, especially
      pregnancy-specific stress, is associated with the risk of spontaneous preterm
      birth. The aim of the present study was to determine the effect of pregnancy
      specific stress on spontaneous preterm birth among Chinese people. MATERIALS AND
      METHODS: A total of 2,189 pregnant women were enrolled and followed up until
      parturition from February 2011 to January 2012. Maternal pregnancy-specific
      stress was assessed using the revised Pregnancy Stress Rating Scale (PSRS) at
      third trimester in pregnancy. Socio-demographic and psychological data were
      collected through interviews, medical, and obstetrical examination records.
      RESULTS: High levels of maternal pregnancy-specific stress during the third
      trimester increased risk of spontaneous preterm birth compared with the low and
      medium levels (adjusted risk ratios, 2.92; 95% confidence interval, 1.12-7.58).
      The first stressor from the revised PSRS includes a risk factor for the safety of
      infants. CONCLUSIONS: High level of pregnancy-specific stress in third trimester
      might predict spontaneous preterm birth.

PMID- 27048028
TI  - Chronic unremitting lower abdominal pain quickly abrogated following treatment
      with amphetamine.
AB  - PURPOSE: To describe a cause and treatment for chronic unremitting lower
      abdominal pain of long duration with unknown origin. MATERIALS AND METHODS: A 50
      year-old woman with 30 years of unexplained right lower quadrant pain was treated
      with dextroamphetamine sulfate. RESULTS: Dramatic complete abrogation of the pain
      occurred within two weeks. The complete relief persisted for two years while she
      remains on therapy. CONCLUSIONS: Symphathetic neural hyperalgesia edema syndrome
      should be considered whenever there is refractory pelvic or abdominal pain.

PMID- 27048029
TI  - Increased tissue permeability and sympathetic nervous system hypofunction may be
      the common link between dysmenorrhea, chronic pelvic pain, Mittelschmerz, and
      Crohn's disease.
AB  - PURPOSE: To determine if severe periovulatory diarrhea in a woman with Crohn's
      disease for just one day may be related to increased permeability of the large
      bowel related to hormonal changes that occur at this time of menstrual cycle.
      MATERIALS AND METHODS: Dextroamphetamine sulfate was given to a woman whose
      Crohn's disease was markedly improved by adalimumab but who still had one day of
      severe diarrhea at mid-cycle. RESULTS: She did not have any diarrhea or frequent
      defecation for the first two periovulatory times before she achieved pregnancy.
      Previously for two years there had not been one month where she did not have the
      severe periovulatory diarrhea. CONCLUSIONS: This case helps support the concept
      that the classic symptoms of Mittelschmerz in women with endometriosis may be
      related to periovulatory events which either cause increased permeability of an
      already compromised tissue, whether it be pelvic or bowel or other tissues, or
      these periovulatory events impair sympathetic nervous system function, which is
      already impaired.

PMID- 27048030
TI  - Comparison of efficacy of different embolic agents on uterine leiomyoma.
AB  - The aim of this study was to explore the efficacies, postoperative side effects,
      and complications of uterine artery embolization (UAE) treatments for uterine
      leiomyoma (UL) with different embolic agents. The study included 107 patients
      with UL that were treated with UAE with polyvinyl alcohol (PVA group) or
      pingyangmycin lipiodol emulsion and silk-segment (PLES group). Six months later,
      the improvement rate of anaemia, the menstrual improvement rate, the incidence
      rate of fever, the disappearance rates of compression symptoms and abdominal
      symptoms in the PVA group were 93.8%, 94.7%, 22.0%, 60.0%, and 88.9%,
      respectively, which showed no significant difference from those in the PLES group
      (90.5%, 92.3%, 84.8%, 53.3%, and 8 1.3%, respectively). The incidence rate of
      fever after embolization in PVA group was significantly lower than that in PLES
      group (c2 = 41.958, p = 0.000). However, the efficacy, improvement rate of
      symptoms, and postoperative side effects of two groups showed no significant
      difference (p > 0.05). PVA and PLES have significant efficacy for UAE treatment
      on patients with UL.

PMID- 27048031
TI  - Dextroamphetamine sulfate treatment eradicates long-term chronic severe headaches
      from temporomandibular joint syndrome--a case that emphasizes the role of the
      gynecologist in treating headaches in women.
AB  - PURPOSE: To test sympathomimetic amine therapy on another type of chronic
      headache syndrome--headaches from temporal mandibular joint (TMJ) syndrome.
      MATERIALS AND METHODS: A woman with 20 years of severe daily pain from TMJ
      refractory to all therapies was treated with dextroamphetamine sulfate. RESULTS:
      The woman showed immediate 100% relief from sympathomimetic amine treatment
      saving her from an expensive jaw breaking operation that was only given a slight
      chance of helping. CONCLUSIONS: Unfortunately most treating physicians are
      unaware of this defect of sympathetic nervous system hypofunction leading to the
      absorption of toxins, which when it involves brain tissue, leads to severe
      headaches. Thus, the gynecologist who is aware of this syndrome because
      sympathetic nervous system hypofunction is the most common cause of pelvic pain,
      may need to intervene in women with chronic headaches, even TMJ.

PMID- 27048032
TI  - Failure of laparoscopic Vecchietti procedure in a woman with androgen
      insensitivity syndrome.
AB  - The authors describe a case with androgen insensitivity syndrome (AIS) who
      underwent the laparoscopic Vecchietti procedure for creation of a neovagina.
      Postoperatively, the patient achieved anatomic success, with a vaginal length of
      about eight cm, and she was advised to use vaginal dilators after discharge. The
      patient reported improved sexual function, but presented about six months later
      for shortening of her vagina and difficult vaginal intercourse. Physical
      examination revealed an obliterated vaginal canal about two cm long. Further
      examination revealed lack of vaginal epithelization. The patient was instructed
      to continue using vaginal dilators in combination with estrogen cream; however,
      the patient did not achieve a vaginal length > two cm. The authors believe that
      the laparoscopic Vecchietti procedure may not be appropriate for women with AIS
      due to lack of epithelization.

PMID- 27048033
TI  - Intra-amnial methotrexate in cervical pregnancy treatment.
AB  - Cervical pregnancy is an extremely rare condition with potential devastating
      consequences if not diagnosed and treated early enough. The authors present a
      case with ultrasound images of early cervical ectopic pregnancy in a woman with a
      history of previous cesarean section who was successfully treated with intra
      amnial methotrexate (MTX).

PMID- 27048034
TI  - Laparoscopic temporary clipping of uterine and ovarian arteries for the treatment
      of interstitial ectopic pregnancy.
AB  - PURPOSE OF INVESTIGATION: To assess the effect of laparoscopic temporary clipping
      of uterine and ovarian arteries for the treatment of interstitial ectopic
      pregnancy. MATERIALS AND METHODS: A 29-year-old woman with vaginal bleeding and
      pelvic pain was admitted to the current clinic. She had secondary amenorrhea for
      nine weeks. Transvaginal ultrasonography revealed normal empty uterus and right
      interstitial ectopic pregnancy with viable embryo. Laparoscopic temporary
      clipping of uterine and ovarian arteries, interstitial pregnancy resection, and
      primary myometrial suturing was performed. RESULTS: Following dissection Latzko
      pararectal space for the visualization of both uterine arteries, four vascular
      clips were placed (two to uterine arteries, two to infundibulopelvic ligaments).
      Excision of interstitial pregnancy and primary myometrial suturing was performed
      with minimal blood loss. The patient was discharged from the hospital after one
      day without any remarkable complications. CONCLUSIONS: To the best of the
      authors' knowledge, this is the first case of interstitial pregnancy that was
      successfully treated by temporary laparoscopic clipping of uterine and ovarian
      vessels prior to interstitial ectopic pregnancy resection.

PMID- 27048035
TI  - Incarceration of gravid uterus by growing subserosal myoma: case report.
AB  - Incarceration of gravid uterus is a rare condition, occurring in one in 3,000 to
      10,000 pregnancies during second trimester. Incarceration of uterus can cause
      several complications, such as uterine rupture, labor dystocia, and
      uncontrollable postpartum hemorrhage. Early diagnosis is important to prevent
      these complications, but there are no standard treatments of incarceration of
      gravid uterus. The authors present a case report of incarceration of gravid
      uterus caused by growing subserosal myoma, which was treated with myomectomy
      during second trimester.

PMID- 27048036
TI  - Laparoscopic subtotal hysterectomy due to giant uterine fibroids: a case report.
AB  - The laparoscopic subtotal hysterectomy (LSH) was given to a patient whose uterus
      was about seven-month pregnanacy because of fibroids. The biggest problem was the
      operation space and visual field was too narrow. Different from the usual
      procedure we do, we morcellated the uterus at the beginning to expand the space.
      Loop ligature of the uterine isthmus was adopted to block uterine ateries before
      morcellating the uterus. After the adnexa exposed totally, we started to cut off
      the round ligaments, proper ligaments and fallopian tubes like usual. It was the
      first time we did LSH for so giant uterus in our hospital, although which was
      usually suitable for the uterus smaller than four-month pregnancy. But if the
      uterine ateries can be blocked effectively at the beginning, the uterus can be
      morcellated and the space will be enlarged. The laparoscopic subtotal
      hysterectomy will also be completed successfully.

PMID- 27048037
TI  - Holt Oram syndrome: a case report and review of the literature.
AB  - Holt Oram syndrome is a rare autosomal dominant syndrome on average, of varying
      severity, which may result in heterogeneous pictures, predominantly with
      involvement of the bony segments of the upper limbs and the cardiovascular
      system. The syndrome is caused by mutations in two genes of the T-box (TBX5, 601
      620 and TBX 3) located on the 12q24.1p. The authors report a case and review the
      literature.

PMID- 27048038
TI  - Medical management of cesarean scar pregnancy at advanced age: case report and
      literature review.
AB  - AIM: Cesarean scar pregnancy is a rare condition that is increasing in frequency
      parallel to the increase in cesarean section rates. The authors hereby discuss a
      case with cesarean scar pregnancy at advanced age that was treated with
      methotrexate (MTX) in Nyala Sudan Turkey Training and Research Hospital.
      CONCLUSION: Cesarean scar pregnancy is a rare type of ectopic pregnancy that is
      increasing in number due to the increase in cesarean deliveries. Clinical
      vigilance is imperative for diagnosis and treatment of this highly mortal and
      morbid entity.

PMID- 27048039
TI  - Urinary catheterization as a successful treatment option for post-cesarean
      section vesicouterine fistula.
AB  - Surgery, the usual treatment option for vesicouterine fistula (VUF), is often
      delayed to allow involution of the uterus. The authors report a case of
      successful treatment with urinary catheterization. A 39-year-old, gravida 7, para
      6, woman presented at term with obstructed labor. She had one previous cesarean
      section followed by a vaginal birth before. She underwent emergency cesarean
      section. She was readmitted after one week because of pelvic collection.
      Aspiration revealed pus and urine. Retrograde cystogram and pelvic MRI confirmed
      the presence of VHF. Urinary bladder catheterization for six weeks resulted in
      the successful treatment of the fistula. Urinary catheterization in the early
      postpartum period can result in resolution of post-cesarean section VUF, without
      delaying surgical intervention if it becomes necessary.

PMID- 27048040
TI  - Acute intestinal obstruction due to a non-involuted uterus after cesarean
      section: case report.
AB  - The involution of the uterus is influenced by a number of factors such as
      advanced childbearing age, electrolyte disturbances, multiparity, repeated
      cesarean sections, and vaginal infections. The authors report the management of a
      clinical case of a 41-year-old female who presented with acute intestinal
      obstruction due to a non-involuted uterus after cesarean section.

PMID- 27048041
TI  - Correlation of serum albumin with the clinical features and prognosis of preterm
      neonates in the neonatal intensive care unit.
AB  - OBJECTIVE: To evaluate the clinical significance of serum albumin (ALB) levels in
      the early evaluation and prognosis of preterm infants in the neonatal intensive
      care units (NICUs). MATERIALS AND METHODS: The authors collected and
      retrospectively analyzed complete clinical records of preterm infants admitted to
      the NICU from July 2012 to March 2013. The cases were divided into three groups
      according to their ALB levels: >= 30 g/L, 25-30 g/L, and <= 25 g/L. RESULTS: The
      mean gestational age in the <= 25 g/L ALB group was significantly higher than
      that in the >= 30 g/L ALB group [(33.41 +/- 2.15) weeks] (p < 0.05). The
      prealbumin, blood platelet, and blood urea nitrogen in the <= 25 g/L ALB group
      were significantly lower than those in the >= 30 g/L ALB group (p < 0.05). In
      addition, serum lactate in the <= 25 g/L ALB group was significantly higher than
      that in the >= 30 g/L ALB group (p < 0.05). CONCLUSION: Serum ALB level increased
      with increasing gestational age. Lower ALB levels were associated with more
      perinatal complications, damage to multiple organs, more severe cases, and
      mechanical ventilation, which resulted in longer hospital stays and poorer
      prognoses.

PMID- 27048042
TI  - Combination of selected biochemical markers and cervical length in the prediction
      of impending preterm delivery in symptomatic patients.
AB  - The pathophysiology of preterm delivery (PTD) is complex and multifactorial.It
      occurs in 8-12% of all deliveries, and the rate of PTD has increased during the
      past years in spite of intensive efforts towards early detection and prompt
      treatment. Fifty-eight pregnant women were eligible to join the study if they
      attended the University Clinic for Gynecology and Obstetrics, Skopje and were
      admitted to Department of High Risk pregnancy Unit with symptoms of preterm labor
      (PTL) (symptoms of uterine activity judged by the assessing physician to be
      indicative of PTL) at 24.0 to 36.6 weeks gestation.Test specimens for fetal
      fibronectin (fFN), phosphorylated insulin like growth factor binding protein 1
      (phIGFBP-1), IL-6, and IL-2R and measuring the cervical length via transvaginal
      ultrasound were performed for each patient. The best statistical model for
      predicting PTL in the present study was to use a combination of the phIGFBP-1
      test, a positive fFN test, cervical length less than 21.5 mm, levels of IL-6
      higher than 1,305 pg/ml in the cervico-vaginal fluid (CVF), and serum levels of C
      reactive protein (CRP) higher than 6.1 mg/L which was excellent at identifying
      the patients that were to deliver within 14 days of admittance.

PMID- 27048043
TI  - Severe antenatal strangulation and sudden fetal death occurs in term: case
      report.
AB  - The authors report a case of a sudden antenatal death, by severe strangulation,
      unlikely related in a term pregnancy; multiple loops of nuchal umbilical cord
      (UC) (ten), rarely describe in literature, were observed around the fetal neck.
      The in utero fetal death (IFD) was suspected by the non-attendance of fetal
      movements and confirmed by US scan. The tight nuchal cord around the neck (tCAN)
      diagnostic was made during caesarean delivery, as it was not discovered in
      pregnancy US scan monitoring nor in the US scan made in emergency. The newborn
      examination shows severe fetal strangulation by the presence of many spires of a
      too long UC (1.50 m). Autopsy was not been accepted by the family. Through this
      reported case the authors wanted to show the difficulties of its diagnosis in
      less developed Sub-Saharan country were US scan practice is not usual.

PMID- 27048044
TI  - Power Moves. Find your strength with a muscle-friendly workout.

PMID- 27048045
TI  - Renal Rules. Your guide to understanding and preventing kidney disease.

PMID- 27048046
TI  - The Insulin Boom. WHY THE COST OF THIS LIFESAVING DRUG IS REACHING NEW HEIGHTS.

PMID- 27048047
TI  - The New Wave.

PMID- 27048048
TI  - What Matters Most. People weigh in on why they use their diabetes management
      products.

PMID- 27048049
TI  - The Right Meter for You.

PMID- 27048050
TI  - The Right CGM for You.

PMID- 27048051
TI  - Go Ahead, Pick Your Pump.

PMID- 27048052
TI  - Set for the Future.

PMID- 27048053
TI  - Pen Pals.

PMID- 27048054
TI  - Think Fast.

PMID- 27048055
TI  - DIET DECISIONS.

PMID- 27048057
TI  - Your food. Relax & Refresh.

PMID- 27048056
TI  - Fight or Flight. Could the body's natural reaction to stress play a role in type
      2 diabetes risk?

PMID- 27048058
TI  - Food Double Up. Takeout at Home.

PMID- 27048059
TI  - Food By the Plate. Fresh Start.

PMID- 27048060
TI  - Advance care planning now covered by Medicare.

PMID- 27048061
TI  - Act now to avoid heavy quality reporting penalties.

PMID- 27048062
TI  - Think about cultural differences with deaf patients to improve outcomes.

PMID- 27048063
TI  - A new order of healthcare delivery. Implementing a population health strategy
      through service line care continuums.

PMID- 27048065
TI  - Implementing patient-centered care in practice.

PMID- 27048064
TI  - Determine provider-level sample sizes for patient satisfaction surveys.

PMID- 27048066
TI  - 4 secrets of patient engagement.

PMID- 27048067
TI  - When flex schedules pay.

PMID- 27048068
TI  - A retrospective on patient-centered care.

PMID- 27048069
TI  - Checks and Balances. As an EMS leader, it is your responsibility to prevent
      theft.

PMID- 27048070
TI  - When a Call Turns Violent. There are strategies you can take to mitigate your
      risk of becoming a victim of violence.

PMID- 27048071
TI  - CASUALTY CARE in the Classroom. Inside the MercyRockford Health System's
      hemorrhage control program for schools.

PMID- 27048072
TI  - The Argument for Public Access Bleeding Kits. If the pros can't get there fast
      enough, how can we stop exsanguination?

PMID- 27048073
TI  - The First Care Provider System: Improving Community Resilience for Unexpected
      Disasters. Why civilians should be prepared to act in mass-trauma events.

PMID- 27048074
TI  - Response to Atypical Incidents: New Demands for EMS. Complex new challenges and
      threats hold more danger for EMS providers.

PMID- 27048075
TI  - Permissive Hypotension in Trauma. Permissive hypotension can be a viable strategy
      in the prehospital setting when used appropriately.

PMID- 27048076
TI  - Protecting Patient Privacy in Community Paramedic Programs. Amid HIPAA and other
      rules, how should you approach the need to share protected health information?

PMID- 27048077
TI  - 9 Seconds. There's no time like today to fix your fitness.

PMID- 27048078
TI  - The power of kindess.

PMID- 27048079
TI  - Nutrition in pressure ulcer prevention: Using a patient-centred approach.

PMID- 27048080
TI  - Statements for the Coroner.

PMID- 27048081
TI  - Inequality. Why does it matter and what should we do about it?

PMID- 27048083
TI  - Clarifying the Intent of Joint Commission Pain Assessment Standards.

PMID- 27048082
TI  - Certification for Patient Blood Management Programs Now Available.

PMID- 27048084
TI  - APPROVED: Standards Changes for Providers of Diagnostic Imaging Services.

PMID- 27048085
TI  - Consistent Interpretation. Joint Commission Surveyors' Observations on
      EC.02.06.01, EP 1.

PMID- 27048086
TI  - APPROVED: Certification Option for Home Care Organizations Providing Community
      Based Palliative Care.

PMID- 27048088
TI  - [Biological multifunctionality of resveratrol and its derivatives].
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phytoalexin known for
      its cardioprotective, neuroprotective, anti-inflammatory, anti-cancer and anti
      aging properties. Unfortunately, low bioavailability and rapid degradation to
      less active metabolites limit the use of this compound in a practical medicine.
      Therefore, lots of attention is paid to synthetic derivatives of resveratrol
      whose biological properties have repeatedly been recognized to be more pronounced
      compared with their natural precursor. This paper presents current state of
      knowledge on the biological activities of resveratrol and its analogues, focusing
      on so far recognized mechanisms of action of these compounds and their potential
      applicability.

PMID- 27048089
TI  - [The holy Graal of biology, or how and why do we age?].
AB  - In recent years, a search for a single, universal cause of aging has been
      replaced by the notion that the aging phenomenon is sufficiently complex to be
      governed by several complementary processes. This situation stems to a large
      extent from a fact that aging may be considered at various levels, starting from
      whole populations, through individual organisms, tissues and organs, ending on
      particular cell types. This complexity has determined currently functioning
      division of aging theories into evolutionary and mechanistic. First group aims at
      answering the question "why do we age?" and determining a biological purpose of
      this process. Mechanistic theories, in turn, try to answer the question "how do
      we age?" in terms of direct reasons of adverse changes that appear in organisms
      with age. The aim of this paper was to collect and present the most important
      theories of aging, pointing--if possible--on reciprocal relationships between
      them.

PMID- 27048090
TI  - [Role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in
      hypertension. Pathogenesis of hypertension and obesity].
AB  - Hypertension (HT), obesity and related metabolic disorders are increasing cause
      diseases with risk of premature death in western societies. Both hypertension and
      obesity are characterized by similar disorders such as chronic low systemic
      inflammation, changes in the vessel wall, abdominal obesity, insulin-resistance
      or dyslipidemia. Chronic, untreated HT leads to adverse changes in internal
      organs like kidney damage, arterial remodeling and hypertrophy of the left
      ventricle. The important role metalloproteinases and their inhibitors (TIMPs) in
      the pathophysiology of hypertension is associated with the degradation of
      vascular wall components, especially collagen and elastin. The activated RAAS
      system (renin-angiotensin-aldosterone) is displaying direct impact in the
      pathogenesis and progress of hypertension. Angiotensin II affects the expression
      and activation of many growth factors, cytokines and MMPs. The fat tissue of
      obese people is in the state of low intensity chronic inflammation and undergoes
      continual process of remodeling. Obesity is one of the direct cause of
      hypertension.

PMID- 27048091
TI  - [Biomineralization--precision of shape, structure and properties controlled by
      proteins].
AB  - ABSTRACT Biomineralization is the process of the formation of crystal structures
      that is under biological control. Living organisms produce structures such as
      bone, teeth, otoliths, otoconia or shells. Although the chemical composition of
      these tissues is similar to corresponding inorganic minerals, their structure and
      mechanical properties differ significantly. This may be because of how they are
      adapted for the functions they perform. The precise control of the formation of
      biominerals starting with the early nucleation stage influences how the final
      tissues are formed. The key factors which determine the size, shape, internal
      structure and properties of biominerals are proteins which control the nucleation
      and growth of the crystals. Biomineralization is a multi-step process involving
      protein-protein interactions, as well as interactions between proteins and
      inorganic fraction. Due to their specific properties, intrinsically disordered
      proteins (IDPs) perform a particularly important role in the control of the
      biomineralization process. This article contains an overview of biominerals that
      are naturally occurring and describes the structures and mineralization
      mechanisms of the most important of them. The main part of this work was
      dedicated to the role of proteins which control crystal growth.

PMID- 27048092
TI  - [Lysophosphatidic acid and malignant neoplasms].
AB  - Lysophosphatidic acid (LPA) is a lipid compound which plays an important role in
      the human body, enabling its proper development and functioning. The
      extracellular LPA is mainly formed of lysophospholipids by the action of
      autotaxin. LPA activates specific G protein coupled receptors on the cell
      surface, which results in activation of intracellular signaling pathways,
      resulting in an increased production of proteins such as VEGF, MMP and uPA. The
      effect is increased cell proliferation, migration, survival and morphological
      changes. Aberrant expression of LPA receptors or autotaxin is present in various
      neoplasms. LPA may be used as a potential diagnostic marker, because its
      concentrations in the plasma of ovarian cancer patients are significantly higher
      than in the control group. Scientific research is focused on the searching for
      the compounds that inhibit the effects of LPA. The promising results of
      preclinical trials suggest potential usefulness of these compounds in the fight
      against cancer.

PMID- 27048093
TI  - [Duplication of DNA--a mechanism for the development of new functionality of
      genes].
AB  - The amplification of DNA is considered as a mechanism for rapid evolution of
      organisms. Duplication can be especially advantageous in the case of changing
      environmental conditions. Whole genome duplication maintains the proper balance
      between gene expression. This seems to be the main reason why WGD is more
      favorable than duplication of the fragments of DNA. The polyploidy status
      disappear as a result of the loss of the majority of duplicated genes. The
      preservation of duplicated genes is associated with the development of their new
      functions. Polyploidization is often noted for plants. However due to sequencing
      technique, the duplications episodes are more frequently reports also for the
      other systematic taxa, including animals. The occurrence of ancient genome
      duplication is also considered for yeast Saccharomyces cerevisiae. The existence
      of two active copies of ribosomal protein genes can be a confirmation of this
      process. Development of the fermentation process might be one of the probable
      causes of the yeast genome duplication.

PMID- 27048094
TI  - [Influence endophytic bacteria to promote plants growth in stress conditions].
AB  - The growth of plants under stress conditions is often assisted by microorganisms
      colonizing the rhizosphere (the root zone of the highest microbial activity). One
      of the most important bacterial groups to encourage the growth of plants (PGPB)
      are endophytes. These microorganisms penetrate living cells of plants and there
      they lead the microbiological activity as endosymbionts. These microorganisms can
      effectively promote the growth of plants under stress conditions and stimulate
      biochemical activities: nitrogen fixation, production of growth hormones (auxins,
      cytokinins and gibberellins), reduction of the high concentration of ethylene as
      well as facilitation of the collection plant minerals and water. This paper is an
      attempt to summarize the current state of knowledge about the biochemical
      activity of bacterial endophytes.

PMID- 27048095
TI  - [PPR proteins--modular factors regulating expression of organellar genomes].
AB  - PPR proteins make up the most numerous family of RNA-binding proteins identified
      to date. They localize almost exclusively to plastids and mitochondria of
      eukaryotic organisms. The most striking feature of this family is the expansion
      of PPR protein-encoding genes in vascular plants, which likely coincided with
      plants colonizing land. PPR proteins participate in stabilizing, editing,
      splicing, degradation and processing of policistronic transcripts, as well as
      translation activation in mitochondria and plastids. Although the number of PPR
      proteins in non-plant organisms is significantly smaller than in plants, they
      still play a crucial role in regulating the expression of mtDNA. Disruptions of
      PPR protein-encoding genes usually result in severe phenotypic consequences.
      Plant PPR proteins bind RNA in a sequence-specific manner, where a single PPR
      motif recognizes an individual nucleotide in a given sequence. This opens up
      possibilities for engineering de novo synthetic protein sequences that would
      interact with precisely determined organellar sequences, thus enabling modulation
      of mtDNA and ctDNA expression.

PMID- 27048096
TI  - [The development, differentiation and composition of flax fiber cells].
AB  - Having vascular origin, flax fiber belongs to the sclerenchyma (steroids) and its
      structure is limited to the cell wall. What determines fiber properties is its
      composition, which in practice means the composition of the secondary cell wall.
      It consists of four main polymers which constitute approximately 90% of the
      fiber: cellulose, hemicellulose, pectin, lignin, and a variety of secondary
      metabolites, proteins, waxes and inorganic compounds. The cell wall is a
      structure with a high complexity of both the composition and interactions of the
      particular elements between themselves. It is determined by differentiation and
      cell growth as well as environmental factors, biotic and abiotic stresses. The
      molecular background of these processes and mechanisms regulating the synthesis
      and rearrangement of secondary cell walls components are being intensively
      studied. In this work we described the latest news about the development,
      composition and metabolism of flax fiber cell wall components together with the
      molecular explanation of these processes.

PMID- 27048097
TI  - Bacterial type AB5 enterotoxins--structure, function and mechanism of action.
AB  - One of the main factors causing bacterial diarrhea are AB5 enterotoxins. This
      group is divided into four families: pertussis toxin, cholera toxin, shiga toxin
      and subtilase cytotoxin. In this review we will describe the activity, structure
      and function of the cholera and shiga toxin families. The AB5 enterotoxins
      contain a catalytic subunit A and pentameric subunit B, which binds to the cell
      surface within lipid rafts. The cholera toxin family cause the constitutive
      activation of Gsa protein, which results in cAMP production, an opening of the
      chloride channels and releases chloride ions into the lumen of the small
      intestine. In contrast, the shiga toxin family has a cytotoxic effect on
      epithelial cells. It can inhibit protein synthesis leading to cell death.
      Although AB5 has a toxic activity, the B5 subunits have a significant potential
      as a transporter for proteins with anticancer activity and as a tool for the
      visualization of lipid rafts and cancer cells.

PMID- 27048098
TI  - [Chemokine CC receptors in the nervous system].
AB  - Chemoattractant cytokines (chemokines) are traditionally known as the important
      mediators of inflammatory processes, however, recently, is also given to their
      other functions in the body. Acting through specific receptors belonging to the G
      proteins they regulate immune processes in the body. About 20 chemokine receptors
      have been identified so far, and 10 of them bind chemokines CC, i.e. having in
      amino-terminal domain 2 adjacent molecules of cysteins. An increasing number of
      data indicates that chemokines and their receptors play an important role in the
      nervous system by acting as trophic factors, increasing the neurons survival,
      neural migration and synaptic transmission. Special role chemokine receptors play
      primarily in the diseases of the nervous system, because due to damage of the
      blood-brain barrier and the blood cerebrospinal fluid barrier, infiltration of
      leukocytes results in development of inflammation. Chemokine CC receptors has
      been shown to participate in Alzheimer's disease, multiple sclerosis, dementia
      associated with HIV infection, stroke or some type of cancers.

PMID- 27048099
TI  - [Links between glycolysis and DNA replication in eukaryotic cells].
AB  - Development of the eukaryotic cell proceeds through sequentional stages of the
      cell cycle, in which there are growth, replication of the genetic material, and
      cell division processes. Many environmental and intracellular factor decides if
      the cell proceeds throughout all stages of the cell cycle or enters the G0
      silencing phase. The cell cycle depends also on metabolic processes, including
      central carbon metabolism and DNA replication. One cof major processes of the
      central carbon metabolism is glycolysis. This is the main pathway of glucose
      metabolism in cells, leading to conversion of this molecule to puryvare. Until
      recently, it was supposed that carbon metabolism and DNA replication are linked
      only indirectly, mostly through energy input, necessary for synthesis of nucleic
      acids, and production of precursors of deoxyribonucleotides. Nevertheless, recent
      studies, described and discussed in this article, suggested that there are much
      more complicated links, perhaps also direct, between these two processes.

PMID- 27048100
TI  - Staging classification for cancer of the ovary and the fallopian tube should
      include in situ carcinoma.

PMID- 27048101
TI  - Management of endometrial cancer: issues and controversies.
AB  - Although endometrial cancer (EC) is the most common gynecologic cancer in
      developed countries, several aspects of its management are still controversial.
      In particular, the need to perform lymphadenectomy represents an important matter
      of discussion. Because of the discordant results in the literature, it is still
      not possible to draft any definitive conclusions regarding the therapeutic value
      of lymph node dissection. The present review discusses the role of
      lymphadenectomy in the setting of EC, risk factors for lymphatic spread,
      identification of patients at risk for lymph node dissemination, and the current
      evidence for adjuvant therapies in patients with positive nodes. Reasons for the
      difficulty in demonstrating any therapeutic value of pelvic and para-aortic
      lymphadenectomy are also discussed.

PMID- 27048102
TI  - The sentinel lymph node biopsy for breast cancer over the years.
AB  - The sentinel lymph node biopsy (SLNB) has progressively substituted complete
      axillary lymph node dissection (CALND), and has dramatically changed breast
      surgery impact on women's psychophysical wellness, reducing surgical morbidity
      while granting an adequate nodal staging. The present authors have seen a gradual
      improvement in the technique in order to reduce both surgical time and the number
      of interventions required, in particular with the intraoperative histological
      examination of sentinel node. Anyway, there is still great debate about the
      predictability of axillary nodal status in case of negative SLNB, as well as in
      case of positive one. Therefore, the authors reviewed the SLNB history and
      discussed its controversial points.

PMID- 27048103
TI  - Adjuvant therapy for Stage IA uterine clear cell carcinoma with no myometrial
      invasion: a critical review of literature.
AB  - Uterine clear cell carcinoma (UCC) is an aggressive variant of endometrial
      cancer. Comprehensive surgical staging is strongly recommended for these patients
      as an upstaging to Stage 3-4 occur in 35-50% of patients. Stage 1A (no myometrial
      invasion) according to FIGO 1988 staging system are seen very rarely in patients.
      In most of the studies, regarding adjuvant treatment, clear cell carcinoma were
      all evaluated with papillary serous carcinoma (PSC). Studies on clear cell
      histology are low in number and also a limited number of patients were included.
      Proportion of patients with complete surgical staging, number of lymph nodes
      excised, and rate of omentectomy were all heterogenous and were not presented
      uniformly in studies. There is no concensus regarding adjuvant treatment for
      Stage 1A patients. Some authors suggest only close observation. Vaginal
      brachytherapy is also strongly recommended in some studies of this review. Multi
      institutional studies with homogenous patient characteristics with homogeneous
      surgery is warranted.

PMID- 27048104
TI  - 'See and treat' approach for high-grade squamous intraepithelial cervical
      lesions.
AB  - PURPOSE OF INVESTIGATION: Evaluation of the over-treatment percentage when
      choosing a 'see and treat' approach in patients with de- viant cervical smear
      test results. MATERIALS AND METHODS: The authors performed a retrospective chart
      review among women who were treated for cytological low-grade squamous
      intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion
      (HSIL) from January 2009 until December 2010. All patients who were treated for
      deviant Pap-smears were analyzed. Patient characteristics were taken into account
      when performing the analysis. Data were analyzed using SPSS. Logistic regression
      was performed to determine the influence of age, smoking, and the reason to
      perform the Pap-smear. RESULTS: A total of 723 patients with deviant Pap-smear
      results were analysed. High-grade cervical intraepithelial neoplasia (CIN) was
      found in 70.3% of the patients with a Pap 3A average dysplasia (low-grade
      squamous intraepithelial lesion). This indicates that 29.7% of the patients would
      be over-treated with a 'see and treat' approach. For Pap 3B (high-grade intra
      epithelial lesion) or higher the over-treatment percentage was 6.7% or less.
      CONCLUSION: Potential risks of a loop electrosurgical excision procedure (LEEP)
      on future pregnancies and fertility should be taken into account when treating
      fertile patients for potential CIN. This should be part of the counseling process
      of patients with a Pap 3A average dysplasia. A 'see and treat' approach can and
      probably should be proposed to patients with a Pap 3B or higher.

PMID- 27048105
TI  - Cancer antigens 19.9 and 125 as tumor markers in patients with mucinous ovarian
      tumors.
AB  - PURPOSE OF INVESTIGATION: To determine the accuracy of carcinoembryonic antigen
      (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA 125 for diagnosis of mucinous
      ovarian cancer (MOC). MATERIALS AND METHODS: Samples were collected
      preoperatively from patients with mucinous ovarian tumor. The following variables
      were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and
      stage were determined according to FIGO-classification. Patients were classified
      into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC.
      RESULTS: The authors studied 94 patients with ages between 15 and 80 years
      (median = 43). Eighty-two patients were NOT MOC (68 mucinous ovarian cystadenomas
      and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were
      in FIGO Stages I or II. No statistically significant differences were found
      between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC
      patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA
      125, we performed a linear regression formula CA 19.9+125 = 0.00102 x CA 19.9 +
      0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and
      0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9
      + 125 exhibited 95.1% specificity and 66.7% sensitivity, increased by 16.7%
      sensitivity compared with using only CA 19.9 or CA 125. CONCLUSIONS: Preoperative
      CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a
      mucinous ovarian tumour is benign or malignant. Using both markers simultaneously
      increases the sensitivity for diagnosis of MOC.

PMID- 27048106
TI  - Plumbagin shows anti-cancer activity in human breast cancer cells by the
      upregulation of p53 and p21 and suppression of G1 cell cycle regulators.
AB  - PURPOSE: Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L.
      (Plumbaginaceae), is known to exhibit proapoptotic, antiangiogenic and
      antimetastatic effects in cancer cells. However, the effect of Plumbagin on
      breast cancer cells and the underlying molecular mechanism has not yet been
      elucidated. MATERIALS AND METHODS: MCF-7 (a human breast cancer cell line) was
      exposed different concentrations of Plumbagin (PG), and the anti-proliferative
      activity was evaluated by the MTT assay. The mechanism of action for the growth
      inhibitory activity of Plumbagin on MCF-7 cancer cells was evaluated using flow
      cytometry for cell cycle distribution, and western blot for assessment of
      expression of potential target proteins. RESULTS: Plumbagin exhibited a
      significant anti-proliferative activity against human breast cancer cells. Flow
      cytometric analysis revealed that Plumbagin caused cell cycle arrest at G1 phase.
      The cell cycle arrest was well correlated with the inhibition of cyclin D1,
      cyclin E, and upregulation of tumor suppressor protein p53. It further inhibited
      the expression of anti-apoptotic Bcl-2 family members such as Bcl-xL and Bcl-2,
      and activated pro-apoptotic proteins like Bax and Bak. CONCLUSION: These findings
      suggest that the anti-proliferative effect of Plumbagin is due to upregulation of
      p53 and p21 and suppression of G1 cell cycle regulators.

PMID- 27048107
TI  - The role of 15-lipoxygenase-1 expression and its potential role in the
      pathogenesis of endometrial hyperplasia and endometrial adenocarcinomas.
AB  - PURPOSE OF INVESTIGATION: To investigate the presence of 15-lipoxygenase-1 (15
      LOX-1) expression and its potential role in the pathogenesis of endometrial
      hyperplasia and endometrial adenocarcinomas. MATERIALS AND METHODS: The authors
      investigated the presence of 15-LOX-1 expression in samples from patients
      diagnosed with normal endometrium (n = 12), endometrial hyperplasia (n = 12), and
      endometrial cancer (n = 12). The immunohistochemical stainings were scored by
      three independent pathologists. A Western blot of 15- LOX-1 determined the
      presence of protein expression in normal endometrium. A Kolmogorov-Smirnov test
      was used to evaluate the data's distribution pattern. For pairwise comparisons of
      the combined scores between groups, the Mann-Whitney U test was used. RESULTS:
      Based on the combined scores for 15-LOX-1 expression, strong immunochemistry
      staining was observed in samples diagnosed with normal endometrium. There was a
      significant difference in 15-LOX-1 expression between normal endometrium and
      endometrial adenocarcinoma (p = 0.03). Comparing tissues from normal endometrium
      and endometrial hyperplasia, there was a decline in the expression from normal
      endometrium to endometrial hyperplasia. However, the difference was not
      statistically significant. CONCLUSION: The present results show that a decrease
      of 15-LOX-1 expression in the endometrial tumorigenesis process, starting from
      normal endometrium to hyperplasia and endometrial cancer, might be a trigger.
      Further studies are required to determine its potential use as a marker in a
      larger randomized multicenter study.

PMID- 27048108
TI  - The expression of osteopontin in breast cancer tissue and its relationship with
      p21ras and CD44V6 expression.
AB  - OBJECTIVE: This study aimed to investigate the expression of osteopontin (OPN),
      p2lras, and CD44V6 in breast cancer tissues, and to analyze the relationships
      between their expression and a patient's clinicopathological characteristics and
      five-year survival rate. MATERIALS AND METHODS: Streptavidin-peroxidase
      immunohistochemistry was used to detect the expression of OPN, p2lras, and CD44V6
      in tissue samples from 96 breast cancer patients, and the multivariate Cox
      proportional hazards model (mCOX-PHM) was used to analyze the factors that affect
      prognosis. RESULTS: Among the 96 breast cancer patients studied, positive
      staining for OPN, CD44V6, and p21ras was observed in 54.2%, 58.3%, and 43.8% of
      samples, respectively. The expression of OPN and CD44V6 were positively
      correlated (r = 0.58), and the expression of OPN and p21ras were also positively
      correlated (r = 0.25). Coexpression OPN, CD44V6, and p21ras was negatively
      correlated with a patient's five-year survival rate (p < 0.05). Kaplan-Meier
      analysis indicated that a patient without OPN, CD44V6, or p21ras expression had
      an improved survival (p < 0.05). Results from the mCOX-PHM analysis indicated
      that CD44V6 expression, the degree of tumor differentiation, and lymph node
      metastasis were all independent factors that indicate prognosis. The combined
      detection of OPN, CD44V6, and p21ras could contribute to a more accurate
      assessment of the biological behavior of breast cancers, and could help to
      indicate the prognosis of breast cancer patients.

PMID- 27048109
TI  - Customized treatment of recurrent gynaecological cancer--the need for
      intraoperative radiation therapy.
AB  - OBJECTIVE: The objective of this retrospective study was to analyze the
      experience with intraoperative radiation therapy (IORT) at the present
      institution and to evaluate its contribution to the management of patients with
      recurrent gynecological cancer. Materials and METHODS: Retrospectively this study
      reviewed data of patients with a gynecological malignancy considered for
      treatment with IORT at Freiburg University Medical Center between 2005 and 2012.
      For this purpose, an analysis of medical records, radiation oncology records,
      operation reports, and follow-up data was conducted. RESULTS: During the period
      of this study, 31 women with gynecological cancer underwent tumor resection in
      combination with IORT. The median age of the patients at the time of IORT was 62
      years (range 38-85). Most patients had undergone surgery at the time of initial
      diagnosis (87%). More than one-third of the patients received prior radiation
      therapy. In addition to that, 52% of the patients had already received
      chemotherapy. The majority of patients suffered from the first relapse of their
      disease. The local recurrence was predominantly located at the pelvic side wall
      (32%) or in intra-abdominal lymph nodes (32%). In 12 patients the authors did not
      apply the planned IORT. Intraoperative complications were rare and IORT was
      tolerated without severe side-effects. Follow-up was 14 months (range 1-65),
      progression free survival (PFS) was five months (range 3-31). CONCLUSIONS: In
      carefully selected patients, IORT and cytoreductive surgery contributed to local
      control and disease palliation. The authors therefore consider IORT an important
      aspect of modern cancer treatment.

PMID- 27048110
TI  - Prevalence and types of cervical human papillomavirus among Turkish women and its
      relationship with demographic factors in a gynecology outpatient clinic.
AB  - PURPOSE OF INVESTIGATION: The purpose of this study was to determine the
      prevalence of various human papillomavirus (HPV) types and its relationship with
      some risk factors among Turkish women. MATERIALS AND METHODS: A total of 673
      patients were included in the study. Cervical samples were taken from the
      patients for routine Pap smear and HPV DNA tests. HPV DNA was studied in the
      cervical smear by using the PCR method. RESULTS: The mean age of the patients was
      40 +/- 10.9 years. Of all patients, 13.5% had a positive HPV DNA test. In
      addition, 5.1% of the patients were HPV type 16 positive, 1.5% were HPV type 18
      positive, 0.6% were HPV type 31 positive, and 0.9% were HPV type 53 positive.
      CONCLUSION: Findings show that awareness should be raised among Turkish women
      regarding HPV infection and vaccination.

PMID- 27048111
TI  - Effects of silencing MTA1 gene by RNA interference on invasion and metastasis of
      endometrial carcinoma.
AB  - OBJECTIVE: The study aimed at the silence effect of MAT1 gene and proteins in
      Ishikawa cell of human endometrial carcinoma cell line through RNAi mediated by
      siRNA and also discussed the effect of MTA1 gene silence on the invasion and
      metastasis of endometrial carcinoma. MATERIALS AND METHODS: According to the
      principle of designing siRNA sequence, siRNA aiming at MTA1 gene (MTA1-siRNA) and
      siRNA used for negative control (Control-siRNA) were designed and synthesized and
      Ishikawa cell was transfected by transfection reagents. RT-PCR method as well as
      western blot was used, respectively, to detect the MTA1 mRNA and protein
      expression of stably transfected cells. Transwell method and scarification
      experiment were adopted to detect the invasion and metastasis of Ishikawa cells.
      RESULTS: The expression results of MTA1 on the levels of mRNA and protein showed
      that the expression level in transfected MTA1-siRNA group was obviously lower
      than that in non-transfected group and transfected control-siRNA group (p <0.05),
      while there was no significant difference between non-transfected group and
      transfected control-siRNA group (p > 0.05). Effective interference on the
      expression of MTA1 gene remarkably lowered the invasion and metastasis of
      endometrial carcinoma Ishikawa cells. CONCLUSION: RNAi aiming at MTA1 can
      effectively inhibit the expression of MTA1 in endometrial carcinoma Ishikawa
      cells and the effective silence of MTA1 can weaken the invasion and metastasis of
      Ishikawa cells, which provides a new strategy for gene therapy of endometrial
      carcinoma and an experimental basis for inhibiting the invasion and metastasis of
      endometrial carcinoma.

PMID- 27048112
TI  - Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced
      stage ovarian cancer.
AB  - PURPOSE OF INVESTIGATION: Extensive surgical procedures to achieve maximal
      cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are
      inevitably associated with postoperative morbidity and mortality. This study
      aimed to identify preoperative predictors of 30-day morbidity after primary
      cytoreductive surgery for advanced stage EOC and to develop a nomogram for
      individual risk assessment. MATERIALS AND METHODS: Patients in The Netherlands
      who underwent primary cytoreductive surgery for advanced stage EOC between
      January 2004 and December 2007. All peri- and postoperative complications within
      30 days after surgery were registered and classified. To investigate predictors
      of 30-day morbidity, a Cox proportional hazard model with backward stepwise
      elimination was utilized. The identified predictors were entered into a nomogram.
      The main outcome was to identify parameters that predict operative risk. RESULTS:
      293 patients entered the study protocol. Optimal cytoreduction was achieved in
      136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity
      could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p =
      0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a
      optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum
      CA125 level, platelet count, and presence of ascites were comparable in both
      groups. CONCLUSIONS: Thirty-day morbidity after primary cytoreductive surgery for
      advanced stage EOC could be predicted by age, hemoglobin, and WHO performance
      status. The generated nomogram could be valuable for predicting operative risk in
      the individual patient.

PMID- 27048113
TI  - G12V Kras mutations in cervical cancer under virtual microscope of molecular
      dynamics simulations.
AB  - Kras mutations and cancers are common and their role in the progression of cancer
      is well known and elucidated. The present work is searching for the most
      deleterious mutation of the four found at codon 12 and 13 of Kras in cervical
      cancers using prediction servers; different servers were used to look into
      different factors that govern the protein function. The in silico results
      predicted G12V to be the most devastating; this particular mutation was then
      subjected to molecular dynamics simulation (MDS) for further analysis. The
      authors' approach of MDSs helped them to place the native and mutant structure
      under virtual microscope and observe their dynamics over time. The results
      generated are enlightening the effect of G12V variation on the dynamics of Kras.
      The structural variation between the native and mutant Kras over 50 nanoseconds
      (ns) run varied at every parameter checked and the results are in excellent
      agreement with the available experimental data.

PMID- 27048114
TI  - Carcinosarcoma of the ovary: a single institution experience and review of the
      literature.
AB  - PURPOSE: To evaluate the management and outcome in patients with advanced stage
      primary carcinosarcoma (CS) of the ovary in a single institution. MATERIALS AND
      METHODS: The authors performed a retrospective analysis of all patients treated
      for CS of the ovary between 1994 and 2011. The medical records, operative reports
      and pathology records were abstracted for baseline characteristics, surgical
      staging, degree of cytoreduction and chemotherapy regimens used. Standard
      statistical methods for analysis of the data were used. RESULTS: A total of 33
      patients with ovarian CS were identified. Of these, 28 records were available for
      analysis. One patient was Stage I (3.5%), two were Stage II (11.1%), 20 were
      Stage III (71.4%), and five (17.9%) were Stage IV. The early stage (Stage I and
      II) patients were excluded from analysis. Of the 25 advanced stage (III and IV)
      patients, 21 (84.0%) were optimally cytoreduced to a residual disease of < one cm
      and four (16.0%) were suboptimally cytoreduced. The median progression free
      survival (PFS) and overall survival (OS) were ten and 21 months, respectively,
      for advanced stages. Twenty-one (75%) patients received adjuvant chemotherapy and
      62% (13 of 21) of treated patients received paclitaxel/carboplatin (T/C) as first
      line chemotherapy. The median PFS and OS were 15.6 and 31.7 months, respectively,
      for those treated with T/C. There was no.difference in PFS (p = 0.42) and OS (p =
      0.91) between the patients who received T/C vs. other chemotherapy regimens as a
      first-line adjuvant chemotherapy. Patients with optimal cytoreduction had an
      improved PFS compared to those with suboptimal cytoreduction (ten vs. four
      monthsp = 0.015); however, there was no difference in OS (21 vs. 13 p = 0.117).
      The two-year OS was 48.0%. In the preset study, PFS was improved in patients who
      were optimally cytoreduced at the time of diagnosis. CONCLUSION: T/C is an active
      regimen in the treatment of ovarian CS and has the potential to be the backbone
      for addition of biologic targeted therapies in the future. For advanced ovarian
      CS the authors recommend optimal cytoreductive surgery followed by T/C
      chemotherapy.

PMID- 27048115
TI  - Association between genetic variants of EGF-containing fibulin-like extracellular
      matrix protein1 gene and sporadic breast cancer in a Chinese Han population.
AB  - PURPOSE OF INVESTIGATION: Genetic susceptibility of breast cancer has been shown
      to be modulated by inheritance of polymorphic genes. EGF-containing fibulin-like
      extracellular matrix protein 1 (EFEMP1) gene played an important role in many
      tumors, including lung cancer, hepatic carcinoma, and prostate cancer. In
      addition, it was importantly downexpressed in breast cancer. The present research
      aimed to assess the association between genetic variations of EFEMP1 and breast
      cancer risk. MATERIALS AND METHODS: The authors genotyped 11 common tagging SNPs
      with an array platform including 960 cases and 972 cancer-free controls of
      Chinese women, according to the HapMap database based on the pairwise linkage
      disequilibrium (LD) r2 threshold of 0.8, minor allele frequency of 0.05. RESULTS:
      Three SNPs were significant associated with breast cancer (rs3791679, p = 0.016,
      OR = 1.21, 95% CI = 1.04-1.41; rs1346786, p = 0.005, OR = 1.31, 95% CI = 1.08 
      1.59; rs727878, p = 0.002, OR = 1.29, 95%CI = 1.10-1.51). Multivariate logistic
      regression analysis revealed that, compared with wild-type carriers in a dominant
      model, a significantly increased breast cancer risk was associated with the three
      identified risk SNPs. Among the selected tagging SNPs, three haplotype blocks
      were identified, and the results of haplotype analysis were consistent with the
      single-locus analysis. The haplotype 'GG' in block 1 and haplotype 'AG' in block
      2 were significantly associated with breast cancer, and had a 54% and 28%
      increased breast cancer risk respectively, compared with their corresponding
      noncarriers. CONCLUSIONS: The present results suggested that the polymorphisms of
      EFEMP1 gene were associated with breast cancer and might contribute to the
      susceptibility of the progression of breast cancer in Chinese Han women.
      Individuals with the risk alleles might increase the risk of breast cancer.

PMID- 27048116
TI  - The mandatory role of groin lymphadenectomy in clinical Stages IB and II vulvar
      cancer.
AB  - PURPOSE OF INVESTIGATION: To analyze the prevalence of inguinofemoral lymph nodes
      metastases in clinical Stages IB-II vulva cancer. MATERIALS AND METHODS: Twenty
      two patients with FIGO Stages IB-II FIGO vulva cancer with no clinically and
      imagistic evidence of nodes metastases were treated in the present clinic. The
      surgical procedures consisted in radical vulvectomy plus inguinofemoral lym-
      phadenectomy. RESULTS: The final pathological result was squamous carcinoma in 20
      patients, vulva melanoma in one, and carcinosar- coma in one. The prevalence of
      positive lymph nodes was 45.4%. The median number of harvested lymph nodes was
      14.0 per groin (between four and 27). Twelve patients (54.5%) developed some
      wound complications, but all were resolved. At the present time, 20 patients are
      alive, but the follow-up period is short for many of them; two patients died of
      disease. CONCLUSION: The prevalence of groin metastases in Stages IB-II vulvar
      cancer is high. A thorough inguino-femoral dissection seems necessary, despite
      the high incidence of wound complications.

PMID- 27048117
TI  - Possible relevance of tumor-related genes mutation to malignant transformation of
      endometriosis.
AB  - OBJECTIVE: Despite studies have suggested that endometriosis has malignant
      potential, the molecular mechanism underlying the malignant transformation of
      endometriosis is poorly understood so far. Endometriosis-associated ovarian
      cancer (EAOC) or ovarian cancer arising from endometriosis (OCEM) may provide an
      ideal model for genetic studies. To investigate the genetic alterations during
      transformation of ovarian endometriosis into cancer, the authors analysed
      mutations of tumour-related genes (PTEN and p53) in EAOC cases (n=23, group 1),
      including 19 cases which were detected co-existence of endometriosis and cancer
      and four cases which fulfilled the histological criteria in malignant
      transformation of endometriosis (OCEMs), and in atypical hyperplasia ovarian
      endometriosis (aEMs) (n = 10, group 2), as well as in solitary ovarian
      endometriosis (EMs) (n = 20, group 3), simultaneously, to study the correlation
      of the two genes in the development and progression of the ovarian endometriosis
      malignancy. MATERIALS AND METHODS: Each paraffin block was sliced into serial ten
      um-thick sections. Extracted DNA was amplified by nested PCR. Mutations of PTEN
      and p53 were examined by bidirectional DNA sequencing. RESULTS: It was
      acknowledged by experiments that the PTEN and p53 mutation frequency in EAOCs
      were significantly higher than that in aEMs and EMs. There was significant
      difference to compare EAOCs with EMs (p < 0.01, p < 0.05), and converse to
      compare with aEMs (p > 0.05), respectively. No definite involvement between the
      frequency of PTEN and p53 mutations in EAOCs and age difference, histological
      type, clinical stage, pathological grade, and whether accompanied by metastasis
      (p > 0.05); however, a decreasing trend of PTEN mutation with the increased age,
      decreased clinical stage and pathological grade, and when accompanied by
      metastasis was detected. Adversely, an increasing trend of p53 mutation was
      represented. In EAOCs group, the authors detected eight PTEN and four p53
      mutation events, respectively. Moreover, one case occurred PTEN and p53 mutation
      simultaneously. With 23 EAOCs, two cases which fulfilled the histological
      criteria in malignant transformation of endometriosis, which may be a specific
      entity distinct from non-endometriosis-associated ovarian cancer, the authors
      named them the OCEMs, occurred PTEN or p53 mutation, respectively. CONCLUSION:
      The present study suggested that the mutation and functional incapacitation of
      certain tumor-related genes may be involved in malignant transformation of
      endometriosis. PTEN mutation is the pristine event, but p53 mutation is the late.

PMID- 27048118
TI  - Interobserver variability and positive predictive value for ultrasonographic BI
      RADS categories requiring pathohistological evaluation.
AB  - OBJECTIVE: The objective of this study was an analysis of interobserver
      variability and positive predictive value (PPV) for BI-RADS categories requiring
      pathohistological evaluation: 4A, 4B, 4C, and 5. MATERIAL AND METHODS:
      Interobserver variability for each of descriptors as well as PPV for final BI
      RADS categories requiring pathohistological evaluation was measured in a
      retrospective study which included 30 ultrasonographic reports, with
      pathohistological verification, randomly selected from ultrasonographic reports
      from Institute for Oncology and Radiology of Serbia where about 1,100 breast
      cancers are verified every year. Ten observers, seven gynecologists, and three
      radiologists, independently rated each ultrasonographic report according to the
      fourth edition of BI-RADS atlas. Interobserver variability was measured with k
      coefficient. RESULTS: There was most conformity for a category of orientation (k
      = 0.79). Substantial degree of conformity was also present for both boundary (k =
      0.71) and shape (k = 0.65) categories. Moderate degree of conformity was achieved
      for posterior features (k = 0.54) and margins (k = 0.41) descriptors, while there
      was poor conformity in echogenicity (k = 0.38). In case of a final score, common
      conformity for all BI-RADS 4A, 4B, 4C, and 5 categories was (k = 0.51); it was
      the greatest for category 5 (k = 0.50), and it was less for categories 4C (k =
      0.37), 4B (k = 0.32), and 4A (k = 0.29). CONCLUSIONS: Interobserver conformity
      for ultrasonographic descriptors and final evaluation of BI-RADS 4A, 4B, 4C, and
      5 categories is good. PPV implies that not only division into categories 4 and 5,
      but also classification into categories 4 and subcategories 4A, 4B, and 4C are
      justified and clinically applicable.

PMID- 27048119
TI  - Role of TWIST2, E-cadherin and Vimentin in epithelial ovarian carcinogenesis and
      prognosis and their interaction in cancer progression.
AB  - Globally, most patients are at late-stage when they have been diagnosed with
      ovarian cancer. Investigating the potential mechanisms involved in tumor
      progression and prognosis is essential for improving treatment options, outcomes,
      and survival. OBJECTIVE: This study elucidated the clinico-pathological
      significance of TWIST2 and the relationship of TWIST2, E-cadherin, and Vimentin
      expression in the progression and prognosis of epithelial ovarian cancer (EOC).
      MATERIALS AND METHODS: Immunohistochemical staining was used to quantify the
      expression and relevance of TWIST2, E-cadherin, and Vimentin in 103 ovarian
      specimens, including 30 cases of benign ovarian tumors, 30 cases of borderline
      ovarian tumors, and 43 cases of EOC. RESULTS: The expression of TWIST2 in the
      cytoplasm may help to maintain characteristics of epithelial cancer cells with E
      cadherin normal membranous expression, while nuclear TWIST2 induces tumor
      translation front with membranous expression of Vimentin, which eventually
      promotes cancer metastasis. Moreover, the upregulation of TWIST2 was also related
      to the aberrant expression of E-cadherin and the increased expression of
      Vimentin, which were reported as important indicators of epithelial-mesenchymal
      transition (EMT). DISCUSSION: The data suggested that co-expression of
      TWIST2/Vimentin was an independent prognostic indicator for both overall survival
      and disease-free survival by multivariate Cox proportional hazards model. TWIST2
      regulates EMT by depriving the epithelial cell phenotype of E-cadherin and
      endowing the mesenchymal cell phenotype with Vimentin, which may be involved in
      the progression and prognosis of ovarian cancer, and TWIST2/Vimentin co
      expression might be a novel indicator with prognostic potential in EOC patients.

PMID- 27048121
TI  - Neoadjuvant chemoradiotherapy followed by radical vulvectomy for adenoid cystic
      carcinoma of Bartholin's gland: a case report and review of the literature.
AB  - Adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare variant and around
      90 cases have been reported. Herein, the authors re port a locally advanced ACC
      of Bartholin's gland that was treated with neoadjuvant chemotherapy followed by
      right radical hemi-vulvectomy and reconstruction with a gracilis musculocutanous
      flap. There was no evidence of recurrence after three years of follow up.

PMID- 27048120
TI  - Outcomes of fertility and pregnancy in patients with early-stage cervical cancer
      after undergoing neoadjuvant chemotherapy.
AB  - OBJECTIVE: To explore the outcomes of oncology, fertility, and pregnancy in
      patients after undergoing neoadjuvant chemotherapy (NACT) followed by fertility
      sparing operations with cervical cancer, and its value in clinical treatment.
      MATERIALS AND METHODS: A total of 11 patients from seven hospitals in Beijing
      with cervical cancer since August 2009 to December 2011, who had undergone
      fertility- sparing treatments were recruited in this study. RESULTS: Among the 11
      patients, there were nine cases of squamous cell carcinoma, two cases of
      adenocarcinoma, one case in Stage IA2, and ten cases in Stage IB1 (FIGO, 2009).
      All of the 11 patients were treated with NACT of one to two cycles before the
      operations, and then they underwent radical trachelectomy (RT) + retroperitoneal
      lymphadenectomy. Eleven patients had completed the follow-up (100%) and the mean
      follow-up was 24.4 months. The outcomes of the oncology and pregnancy are as
      follows: no patient recurred after fertility-sparing treatments; in seven
      patients seeking pregnancy after the treatments, three pregnancies occurred in
      two women. CONCLUSIONS: NACT+RT, as a fertility-sparing treatment for young women
      with bulky early-stage cervical cancer and its outcomes in fertility and
      pregnancy are satisfactory, however its safety needs to be studied further.

PMID- 27048122
TI  - Non-Hodgkin lymphoma of the female genital tract mimicking primary gynecological
      tumors: a single-center series of 3 cases.
AB  - INTRODUCTION: Malignant lymphoma of the female genital tract is quite rare and
      its presentation may resemble that of other, more common tumors, causing
      confusion for clinicians. CASE HISTORY: The authors report three patients with a
      non-Hodgkin lymphoma (NHL) involving the female genital tract: two cases involved
      the ovary and one involved the uterus. In all patients, the genital tract was the
      initial site of clinical presentation of a B cell lymphoma. One patient was
      diagnosed postoperatively and subsequently received chemotherapy; the other two
      patients were diagnosed by imaging-guided biopsy and were successfully managed by
      chemotherapy without resection surgery. Two patients were alive, without evidence
      of disease, and one patient was alive with disease at their most recent follow-up
      visit. CONCLUSION: The authors' experience emphasizes that lymphoma should be in
      the differential diagnosis of pelvic gynecological malignancies, and its
      clinical, biological, and radiological signs must be actively sought. Imaging
      guided biopsy should be performed to avoid unnecessary surgery.

PMID- 27048123
TI  - A uterus soaked in blood with low haemoglobin in a case of unrecognized uterine
      sarcoma.
AB  - INTRODUCTION: Uterine sarcomas are rare and aggressive tumors. In some cases they
      can cause rupture of the uterus with or without clinical and radiological
      symptoms. Therefore, it is important to observe patients with clinical and/or
      radiological suspicion of sarcoma, even when there are no clinical
      manifestations. CASE REPORT: A 71-year old woman, who was under the authors'
      observation for pain in the right iliac fossa. The US and the CT scan showed an
      abdominal-pelvic mass.Laboratory tests showed a slight but progressive reduction
      of haemoglobin, which could not be explained by the clinical symptoms and by the
      results of the imaging tests. During the surgical intervention, a small amount of
      peritoneal fluid, an increased uterine volume, and a subverted anatomy were
      observed A haematoma was found in the uterus and this could explain the
      progressive reduction of haemoglobin and the very low presence of peritoneal
      effusion. CONCLUSION: The rupture of the uterus could not have been suspected as
      the patient did not have any type of symptoms, except for the slow and
      progressive reduction in the haemoglobin value. Therefore, it is important to
      observe patients with clinical and/or radiological suspicion of sarcoma, even
      when there are no clinical manifestations.

PMID- 27048124
TI  - Skin metastases of vulvar squamous cell carcinoma. Presentation of a rare case.
AB  - Skin metastases secondary to vulvar carcinoma is an infrequent clinical entity.
      The authors describe a case of squamous vulvar carcinoma, which presented with
      cutaneous involvement as a part of distant spread. After a radical vulvectomy,
      bilateral inguino-femoral lymphadenectomy, and adjuvant radiotherapy, the patient
      developed multiple cutaneous metastases in lower extremities. This case was
      unique in presentation, with skin metastases secondary from vulvar carcinoma, and
      indicated advance disease and poor prognosis.

PMID- 27048125
TI  - Primary small cell carcinoma of the vagina with pulmonary metastasis: a case
      report.
AB  - Primary small cell carcinoma of the vagina is extremely rare; no standard
      treatment has been established despite it being highly aggressive. Here, the
      authors report on a 43-year-old patient who had a mass on the clitoris and no
      uterine or bilateral adnexal involvement. Vaginal wall biopsy revealed malignant
      small cell carcinoma. The carcinoma was composed of epithelial cells with round,
      hyperchromatic nuclei containing few distinct nucleoli, and scanty cytoplasm.
      Chest computerized axial tomography and pathological bronchoscopy revealed
      bilateral pulmonary metastases. She received radiotherapy combined with six
      cycles of chemotherapy (paclitaxel plus cisplatin), and achieved complete
      response, with complete suppression of the mass and lung metastases. There was no
      sign of tumor recurrence or distant metastases after 21 months of follow-up.

PMID- 27048126
TI  - Anti-adhesive film mimicking local recurrence during follow up after surgical
      treatment of gynecologic malignancy.
AB  - A 51-year-old woman received a laparoscopic surgical staging operation due to
      endometrial carcinoma. Adjuvant pelvic radiotherapy was performed when the
      endometrial carcinoma was staged at FIGO Stage IIIC1, adnexa metastasis. Three
      months completing adjuvant pelvic radiotherapy, a 2.5-cm vaginal stump mass was
      found by abdomino-pelvic computed tomography (AP-CT). To rule out local
      recurrence, diagnostic laparoscopic exploration was performed. The pathologic
      report revealed chronic inflammation due to the presence of a foreign body. To
      avoid unnecessary surgery during the follow-up of patients with gynecologic
      malignancies, anti-adhesive material should be avoided which can possibly cause a
      lesion mimicking local recurrence.

PMID- 27048127
TI  - Squamous cell carcinoma in situ lining the uterine cavity.
AB  - Cervical intra-epithelial neoplasia is a very common and well-known pathology.
      However superficial spreading of this lesion is very rare. The authors present a
      case of a 72-year-old woman with an abdominal mass, who had previously undergone
      a cervical conisation for a high-grade cervical intra-epithelial neoplasia.
      Anatomo-pathological examination of the mass showed a large distended fluid
      filled uterus with the entire endometrium replaced by a high-grade squamous cell
      lesion. There were only micro-invasive foci found. The authors performed a
      literature search in PubMed with the following MeSH-terms: "squamous cell
      carcinoma" and "endometrium". Other articles were selected out of the references
      of previously found articles. Only 31 similar cases were found. The presentation
      of the cases is varies extremely and a long-term prognosis is not yet known.

PMID- 27048128
TI  - Krukenberg tumor in a 18-year-old-female: a rare case.
AB  - BACKGROUND: Krukenberg tumors mostly occur after 40 years. Metastatic ovarian
      tumors in young age are very rare. CASE: A 18-year-old female presented with
      colon cancer which was accompanied by Krukenberg tumor. The present case was a
      very rare case of metastatic ovarian tumor in very young age. The present patient
      presented with abdominal pain. On examination, colon tumor was detected and
      bilateral ovary were almost normal with only slight swelling. During the
      operation for colon tumor, biopsy of bilateral ovary was performed for
      histopathological evaluation. Although there were no specific findings in
      bilateral ovary, microscopic examination revealed poorly differentiated
      adenocarcinoma, diffusely invading the ovarian parenchyma. Diagnosis of colon
      cancer was made postoperatively and ovarian Krukenberg tumor was confirmed.
      CONCLUSION: In case of suspecting colon cancer even in very young patient with
      normal ovary, biopsy of ovary should be considered for the diagnosis of
      Krukenberg tumor.

PMID- 27048129
TI  - Enormous ovarian fibroma with elevated Ca-125 associated with Meigs' syndrome.
      Presentation of a rare case.
AB  - In medicine, Meigs' syndrome is the triad of ascites, pleural effusion, and
      benign ovarian tumor (fibroma, Brenner tumour, and occasionally granulosa cell
      tumour). It resolves after the resection of the tumor. Because the
      transdiaphragmatic lymphatic channels are larger in diameter on the right, the
      pleural effusion is classically on the right side. The etiologies of the ascites
      and pleural effusion are poorly understood. Atypical Meigs'
      syndrome,characterized by a benign pelvic mass with right-sided pleural effusion
      but without ascites, can also occur. As in Meigs syndrome, pleural effusion
      resolves after removal of the pelvic mass. The authors would like to share their
      own experience of a case of Meigs' syndrome associated with an enormous ovarian
      fibroma and elevated Ca-125.

PMID- 27048130
TI  - Solitary fibrous mass of the omentum mimicking an ovarian tumor: case report.
AB  - There are some pelvic masses which are difficult to correctly classify as
      malignant or benign. The decision concerning method and choice of surgical
      intervention is not simple in this situation. Some tumors are extremely rare and
      need to be presented in the literature. The authors report a rare case of fibrous
      tumor of the omentum simulating a malignant ovarian tumor, which ultimately
      resulted to be a primary solitary fibrous tumor of the omentum. Ultrasound
      findings are mostly precise prognostic tools according ovarian masses. However,
      from time to time, Doppler blood flow examination may present false positive
      results.

PMID- 27048131
TI  - Leiomyosarcoma of cervical stump following subtotal hysterectomy: a case report
      and review of literature.
AB  - BACKGROUND: Leiomyosarcoma that arises in the uterine cervix stump after subtotal
      hysterectomy is exceedingly rare. Only one case has been documented. The authors
      report an unusual case of leiomyosarcoma that arose in the cervix stump. CASE
      PRESENTATION: A 46-year-old female presented with a one-month history of vaginal
      bleeding. Vaginal and ultrasonography examination revealed a mass in the cervix.
      The patient underwent radical resection of the cervix, bilateral salpingo
      oophorectomy, and pelvic lymphadenectomy. Chemotherapy and radiotherapy was given
      after the operation. The patient suffered from severe menopausal symptoms and
      received hormone replacement therapy. She eventually committed suicide.
      CONCLUSION: Given the rarity of cases of leiomyosarcoma of cervical stump, its
      proper treatment remains to be determined. In dealing with benign uterus
      diseases, we should pay adequate attention in retaining the cervix. If the cervix
      is retained, patients require appropriate follow-up. The authors hope that this
      work will benefit the fields of gynecology and oncology.

PMID- 27048132
TI  - [On development of partnership between Rospotrebnadzor research institutions and
      socially responsible business community for sanitary epidemiologic well-being of
      population].
AB  - The article covers systemic approaches to managing risks for public health, and
      development of partnership between Rospotrebnadzor institutions and socially
      responsible business community.

PMID- 27048133
TI  - [Methodology of assessing and evaluating public health risk in legal regulation
      of sanitary epidemiologic well-being of population].
AB  - The authors describe method to assess and manage risk for public health in system
      of legal regulation of sanitary epidemiologic well-being of population. Scheme of
      assessment and management of occupational risks is presented.

PMID- 27048134
TI  - [On industrial conditionality of diseases among copper melting enterprise
      workers].
AB  - Health state of workers in hazardous conditions of copper melting enterprise
      depends on wide spectrum of somatic occupationally conditioned diseases. Economic
      damage from workers' health disorders due only to cardiovascular diseases can be
      considerable. To reduce this damage, hygienic measures are necessary to improve
      work conditions, to preserve occupational fitness of the workers, other measures
      to diminish controllable factors of vascular risk and to prevent occupationally
      conditioned cardiovascular diseases.

PMID- 27048135
TI  - [Economic aspects of occupationally conditioned diseases risk (exemplified by
      potassium salts extraction enterprises].
AB  - Economic evaluation of workers' health disorders risk could include cost
      equivalent not of health itself, but a prevented risk for worker's health. The
      authors evaluated a potential underproduced output during disablement period and
      changes of tax proceeds (except gross domestic product losses). This approach was
      tested in evaluating risk for.health of workers engaged into underground mining
      on potassium salts extraction enterprise. Mathematic models of unfavorable
      effects development enabled to follow dynamics of these effects and forecast
      possible development of diseases in the studied workers group.

PMID- 27048136
TI  - [Influence of ambient air pollutants released by metallurgic enterprises on
      public].
AB  - State of ambient air in resident area in Norilsk city, on background of
      considerable and persistently high releases of chemical pollutants by major
      metallurgic industrial enterprises, forms risks for public health--that is
      supported by highly prevalent diseases of affected organs and systems in the city
      residents. Preserving sanitary epidemiologic well-being of this territory
      requires specification and implementation of hygienic, organizational, social
      measures to protect population dwelling in unfavorable regions.

PMID- 27048137
TI  - [Algolization of drinkable water basins in Nizhny Tagil industrial complex].
AB  - The article covers experience of biologic rehabilitation through correction of
      algocenosis (algolization) of drinkable water basins in Nizhny Tagil industrial
      complex. Biologic rehabilitation of Chernoistochnik and Verhne-Vyisky drinkable
      water basins in 2011-2012 considerably improved water quality in ecologic
      hydrochemical and hydrobiologic parameters--that was proved by absent water
      contamination with blue-green algae, lower saprobiont index. Results also are
      significant lower concentration of pollutants--heavy metals (ferrum, manganese,
      copper), oil products, decreased odor and and better water quality in
      hydrochemical parameters to second class according to water pollution index.

PMID- 27048138
TI  - [Possibility of minimizing capital costs for organization of sanitary protection
      zone of enterprise].
AB  - The article covers topic of sanitary protection zones, from a viewpoint of
      decided ecologic solutions and economic content, and approach to calculation of
      the most optimal correlation between them.

PMID- 27048139
TI  - [Clinical and hygienic evaluation of health state of copper production workers in
      Far North].
AB  - The article covers disclosure of fuctional and clinical, laboratory markers of
      health disorders among workers engaged in major occupations of copper processing
      enterprise. These markers are used for early diagnosis and prevention of
      respiratory diseases.

PMID- 27048140
TI  - [Healthy lifestyle formation and lower dependence on atmosphere oxygen in
      working].
AB  - Studies covered 38 males in laboratory and 81 males in industrial conditions of
      13 metallurgic enterprises and revealed some reliable phenomena caused by dry
      voluntary apnea of 10-60 seconds. At muscular rest and during physical exertion,
      evidences are that voluntary apnea forms transitory hypercapnic portion of blood
      in pulmonary arterial flow. First finding is that this portion in other blood
      behaves as an anabolic wave carrying increased concentration of low-molecular CO2
      material and releasing additional (wave, according to authors) O2 from its depot
      in the body. This oxygen, in conditions of increased blood pressure due to apnea,
      is used for synthesis of additional ATP. These phenomena characterize formation
      and development a new beneficial physiologic system in workers--a functional
      system of motivation to healthy lifestyle.

PMID- 27048141
TI  - [Comorbid state in coal miners suffering from lumbosacral radiculopathy].
AB  - The authors considered topics of occupational and general comorbidity of
      occupational lumbosacral radiculopathy in coal miners (2791 examinees) observed
      over 1976-2014 in occupational center. In patients having lumbosacral
      radiculopathy without occupational mixed diseases, the occupational disease was
      diagnosed at the age 3-5 years younger, and 2-4 years earlier from primary visit.
      Analysis of occurrence of general comorbid conditions with lumbosacral
      radiculopathy revealed some regularities: patients manifested with symptoms due
      to vibration have more frequent arterial hypertension than in those with
      lumbalgia, whereas in risk group of hearing affected by noise IHD was more
      possible.

PMID- 27048143
TI  - Editorial: The Acute Management of Pediatric Heart Failure.

PMID- 27048142
TI  - [FEDERAL CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS, PREVENTION AND TREATMENT
      OF PNEUMOCONIOSIS].
AB  - The purpose of development of this clinical practice guidelines was to provide
      evidence-based protocols that help the practitioner and the patient make the
      right decision for the health assessment, treatment and prevention of
      pneumoconiosis. Pneumoconiosis is the interstitial lung disease of occupational
      origin caused by prolonged inhalation of inorganic dust, characterized by chronic
      diffuse aseptic inflammation in lung tissue with the development of pulmonary
      fibrosis. Currently, thereare no treatment that provide a cure pulmonary fibrosis
      and changes in the dynamics of decline in lung function. Regular, individually
      tailored treatment should be directed to the pathogenic mechanisms and some
      clinical symptoms of pneumoconiosis, as well as the prevention of complications.
      To enhance the effect of pharmacotherapy is recommended to use non-drug therapies
      that enhance the functionality of the respiratory system.

PMID- 27048144
TI  - Pharmacologic Approach to Heart Failure in Children.
AB  - Heart failure may result from a wide variety of causes and present with varying
      degrees of severity. In large part patients present with varying degrees of
      congestion and compromised cardiac output. In this review a pathophysiologic
      construct is provided to guide the pharmacologic management of acute heart
      failure that leads to decreased congestion and improved cardiac output.
      Pharmacologic therapies that are used to treat chronic heart failure are also
      highlighted and provide the framework for transitioning from acute to
      preventative pharmacologic strategies. 

PMID- 27048145
TI  - Mechanical Circulatory Support in Children.
AB  - The field of pediatric mechanical circulatory support has undergone a significant
      evolution with the advent of devices designed for children and the implementation
      of new strategies for deployment. With the ongoing shortage of organs the demand
      for new devices specifically designed for children will only increase. This
      review discusses the evolution of mechanical circulatory support, available
      devices, and the implementation of new strategies for their deployment. 

PMID- 27048147
TI  - Prognostic implications of heart failure with preserved ejection fraction in
      patients with an exacerbation of chronic obstructive pulmonary disease.

PMID- 27048146
TI  - Hormonal stimulation of starfish oocytes induces partial degradation of the 3'
      termini of cyclin B mRNAs with oligo(U) tails, followed by poly(A) elongation.
AB  - In yeast, plant, and mammalian somatic cells, short poly(A) tails on mRNAs are
      subject to uridylation, which mediates mRNA decay. Although mRNA uridylation has
      never been reported in animal oocytes, maternal mRNAs with short poly(A) tails
      are believed to be translationally repressed. In this study, we found that 96% of
      cyclin B mRNAs with short poly(A) tails were uridylated in starfish oocytes.
      Hormonal stimulation induced poly(A) elongation of cyclin B mRNA, and 62% of long
      adenine repeats did not contain uridine residues. To determine whether uridylated
      short poly(A) tails destabilize cyclin B mRNA, we developed a method for
      producing RNAs with the strict 3' terminal sequences of cyclin B, with or without
      oligo(U) tails. When we injected these synthetic RNAs into starfish oocytes prior
      to hormonal stimulation, we found that uridylated RNAs were as stable as
      nonuridylated RNAs. Following hormonal stimulation, the 3' termini of short
      poly(A) tails of synthesized RNAs containing oligo(U) tails were trimmed, and
      their poly(A) tails were subsequently elongated. These results indicate that
      uridylation of short poly(A) tails in cyclin B mRNA of starfish oocytes does not
      mediate mRNA decay; instead, hormonal stimulation induces partial degradation of
      uridylated short poly(A) tails in the 3'-5' direction, followed by poly(A)
      elongation. Oligo(U) tails may be involved in translational inactivation of
      mRNAs.

PMID- 27048148
TI  - The Importance of Awareness and Education in Patients with Breast Cancer-Related
      Lymphedema.
AB  - Upper extremity lymphedema occurs in one of five women after breast cancer
      treatment and causes significant morbidity. Women often report being uninformed
      regarding awareness of lymphedema and other side effects after the cancer
      surgery. The aim of the study was to assess the postoperative information and
      education about lymphedema in patients with lymphedema related to breast cancer
      surgery in the rehabilitation unit of a tertiary hospital. One hundred eighty
      patients who had admitted to lymphedema rehabilitation unit between September
      2013 and February 2015 were recruited to the study. The demographic properties of
      women, duration, and grade of lymphedema were recorded. The patients were asked
      whether they had received any information about awareness of lymphedema or
      whether they have been educated for reducement of the risk of lymphedema after
      the breast cancer surgery. One hundred eighty women with a mean age of 52.9 +/-
      10.7 years (27-53) and with a mean lymphedema duration of 19.8 +/- +39.4 months
      were included. Ninety-eight (54.4 %) patients had grade 1, 80 (44.4 %) patients
      had grade 2, and 2 (1.11 %) patients had grade 3 lymphedema. Among the
      participants, only 35 (19.5 %) had reported that they had received information or
      education about lymphedema. One hundred forty-five patients (80.5 %) were not
      informed or trained about the development of lymphedema. The degree and duration
      of lymphedema were lower in patients that had been informed or educated about
      lymphedema as compared to the patients who had not been informed or educated, but
      the difference was not statistically significant (p = 0.052). Only a minor group
      of patients (19 %) had received information and education about lymphedema and
      there is an unmet need for education or information about lymphedema after breast
      cancer treatment, especially in developing countries. The nonsignificant
      correlation between education and the degree and duration of lymphedema was
      thought to be related with the incongrous numbers of the subgroups. In conclusion
      with the growing population of breast cancer survivors, patient awareness and
      education about postoperative lymphedema risk after the cancer surgery is
      warranted.

PMID- 27048149
TI  - Health Literacy in Canada; a Primer for Students: Laurie Hoffman-Goetz, Lorie
      Donelle, and Rukhsana Ahmed : Canadian Scholars Press, Toronto, Ontario, Canada,
      2014.

PMID- 27048150
TI  - Resective surgery for focal cortical dysplasia in children: a comparative
      analysis of the utility of intraoperative magnetic resonance imaging (iMRI).
AB  - PURPOSE: Seizure freedom following resection of focal cortical dysplasia (FCD)
      correlates with complete resection of the dysplastic cortical tissue. However,
      difficulty with intraoperative identification of the lesion may limit the ability
      to achieve the surgical objective of complete extirpation of these lesions.
      Intraoperative magnetic resonance imaging (iMRI) may aid in FCD resections. The
      objective of this study is to compare rates of postoperative seizure freedom,
      completeness of resection, and need for reoperation in patients undergoing iMRI
      assisted FCD resection versus conventional surgical techniques. METHODS: We
      retrospectively reviewed the medical records of pediatric subjects who underwent
      surgical resection of FCD at Children's National Medical Center between March
      2005 and April 2015. RESULTS: At the time of the last postoperative follow-up, 11
      of the 12 patients (92 %) in the iMRI resection group were seizure free (Engel
      Class I), compared to 14 of the 42 patients (33 %) in the control resection group
      (p = 0.0005). All 12 of the iMRI patients (100 %) achieved complete resection,
      compared to 24 of 42 patients (57 %) in the control group (p = 0.01). One (8 %)
      patient from the iMRI-assisted resection group has required reoperation, compared
      to 17 (40 %) patients in the control resection group. CONCLUSION: Our results
      suggest that the utilization of iMRI during surgery for resection of FCD results
      in improved postoperative seizure freedom, completeness of lesion resection, and
      reduction in the need for reoperation.

PMID- 27048151
TI  - Cardiovascular mortality sex differentials in selected East Asian and Western
      populations.
AB  - BACKGROUND: Explaining patterns in the sex ratio (male/female) of cardiovascular
      disease (CVD) mortality would improve understanding of mortality transitions
      under modernisation. Little research has examined secular trends in this ratio
      across populations, taking age and cohort into account. We examine cohort effects
      in the ratios of CVD mortality (including ischaemic heart disease and
      cerebrovascular disease) among 4 East Asian populations that vary in the timing
      of their modernisation, and assess the effect of smoking on these patterns in
      comparison with Western populations. METHODS: The sequential method for log
      linear models is applied to analyse age, period and cohort effects for sex
      ratios. Age and cohort effects are fitted first, with population as offset;
      period effects are fitted in a second model using the fitted values from the
      first model as the offset. Lung cancer mortality serves as a proxy for smoking.
      RESULTS: Increases in sex ratios of CVD mortality began in earlier cohorts in
      Western than in East Asian populations. Once begun, increases were more rapid in
      East Asia. The cohort effect for the sex ratio of CVD mortality differs from that
      for lung cancer mortality. Trends in sex ratios of CVD mortality by cohort are
      similar before and after adjustment for lung cancer mortality in East Asia; the
      increasing trend across 1900-1945 cohorts is maintained in Western populations
      after adjustment. CONCLUSIONS: The sex ratio of CVD mortality has increased
      across successive cohorts living in increasingly modernised environments. There
      is scant evidence that this increase is attributable to changing sex-specific
      rates of smoking.

PMID- 27048153
TI  - Enteric parasitic infection among HIV-infected patients visiting Tribhuvan
      University Teaching Hospital, Nepal.
AB  - BACKGROUND: Enteric parasitic infection among human immunodeficiency virus (HIV)
      patients has been a significant health problem in developing countries like
      Nepal. This study was undertaken to access the burden of enteric parasites among
      HIV patients and its association with their immune status. METHODS: A cross
      sectional study, involving 112 HIV sero-positive patients was conducted in
      Tribhuvan University Teaching Hospital, Public Health Research Laboratory,
      Kathmandu, Nepal from July 2011 to June 2012. The fecal samples were processed by
      direct-smear technique, in both normal saline solution and 1% iodine solution as
      well as modified acid fast staining (Kinyoun's method) after formalin ether
      concentration and Sheather's sucrose flotation for the identification of enteric
      parasites. RESULTS: Infection with one or more parasite was seen in 33.9% (n =
      38) of the cases enrolled in the study, with the parasite prevalence rate of
      41.1% (n = 46). Literacy (OR = 1.9, 95% CI 0.9-4.3) and CD4 T-cell count <200 (OR
      = 2.5, 95% CI 1.1-5.7) were found to be associated with enteric parasite
      infection. Similarly, CD4 T-cell count <200 was found to be associated with
      opportunistic parasitic infection (OR = 3.2, 95% CI 1.2-7.8). Among opportunistic
      parasites, Giardia duodenalis was the most common (28.3%, n = 13) one. Multi
      parasitism was observed in six patients (15.8%). CONCLUSION: Enteric parasitic
      infections are common in HIV-infected people. The poor immune status as indicated
      by low CD4 T-cell count may account for higher risk of both opportunistic and non
      opportunistic enteric parasitic infection.

PMID- 27048152
TI  - Correlates of cocaine use during methadone treatment: implications for screening
      and clinical management (ANRS Methaville study).
AB  - BACKGROUND: Cocaine use is frequent in patients receiving methadone maintenance
      treatment (MMT) and can jeopardize their treatment response. Identifying clinical
      predictors of cocaine use during methadone treatment can potentially improve
      clinical management. We used longitudinal data from the ANRS Methaville trial
      both to describe self-reported occasional and regular cocaine use during MMT and
      to identify clinical predictors. METHODS: We selected 183 patients who had data
      on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483
      visits. The outcome was "cocaine use" in three categories: "no," "occasional,"
      and "regular" use. To identify factors associated with the outcome over time, we
      performed a mixed multinomial logistic regression. RESULTS: Time on methadone was
      significantly associated with a decrease in occasional but not in regular cocaine
      use from 14.7% at M0 to 7.1% at M12, and from 10.7% at baseline to 6.5% at M12,
      respectively. After multiple adjustments, opiate injection, individuals screening
      positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those
      presenting depressive symptoms were more likely to regularly use cocaine.
      CONCLUSIONS: Although time on MMT had a positive impact on occasional cocaine
      use, it had no impact on regular cocaine use. Moreover, regular cocaine users
      were more likely to report opiate injection and to present ADHD and depressive
      symptoms. Early screening of these disorders and prompt tailored pharmacological
      and behavioral interventions can potentially reduce cocaine use and improve
      response to MMT. TRIAL REGISTRATION: The trial is registered with the French
      Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the
      European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008
      001338-28, the ClinicalTrials.gov Identifier: NCT00657397 , and the International
      Standard Randomised Controlled Trial Number Register ISRCTN31125511.

PMID- 27048154
TI  - Coronavirus Infection and Diversity in Bats in the Australasian Region.
AB  - Following the SARS outbreak, extensive surveillance was undertaken globally to
      detect and identify coronavirus diversity in bats. This study sought to identify
      the diversity and prevalence of coronaviruses in bats in the Australasian region.
      We identified four different genotypes of coronavirus, three of which (an
      alphacoronavirus and two betacoronaviruses) are potentially new species, having
      less than 90% nucleotide sequence identity with the most closely related
      described viruses. We did not detect any SARS-like betacoronaviruses, despite
      targeting rhinolophid bats, the putative natural host taxa. Our findings support
      the virus-host co-evolution hypothesis, with the detection of Miniopterus bat
      coronavirus HKU8 (previously reported in Miniopterus species in China, Hong Kong
      and Bulgaria) in Australian Miniopterus species. Similarly, we detected a novel
      betacoronavirus genotype from Pteropus alecto which is most closely related to
      Bat coronavirus HKU9 identified in other pteropodid bats in China, Kenya and the
      Philippines. We also detected possible cross-species transmission of bat
      coronaviruses, and the apparent enteric tropism of these viruses. Thus, our
      findings are consistent with a scenario wherein the current diversity and host
      specificity of coronaviruses reflects co-evolution with the occasional host
      shift. 

PMID- 27048155
TI  - A comparison of novel, selective fatty acid amide hydrolase (FAAH),
      monoacyglycerol lipase (MAGL) or dual FAAH/MAGL inhibitors to suppress acute and
      anticipatory nausea in rat models.
AB  - RATIONALE: Drugs that block fatty acid amide hydrolase (FAAH, which elevates
      anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2
      arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory
      nausea in human patients. OBJECTIVE: This study aims to evaluate the relative
      effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and
      anticipatory nausea in rat models. MATERIALS AND METHODS: AM4302, a new dual
      MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301,
      and new selective FAAH inhibitor, AM4303, for their potential to reduce acute
      nausea (gaping in taste reactivity) and anticipatory nausea (contextually
      elicited conditioned gaping) in two rat models. RESULTS: Our in vitro studies
      indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively,
      with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200
      nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM,
      respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and
      1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301,
      suppressed acute nausea in a CB1-mediated manner, when delivered systemically or
      into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor,
      AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing
      acute nausea, it was more effective than both in suppressing anticipatory nausea.
      CONCLUSIONS: Dual FAAH and MAGL inhibition with AM4302 may be an especially
      effective treatment for the very difficult to treat symptom of anticipatory
      nausea.

PMID- 27048156
TI  - Persistence and amplitude of cigarette demand in relation to quit intentions and
      attempts.
AB  - INTRODUCTION: The cigarette purchase task (CPT) is a method that can be used to
      assess the relative value of cigarettes. Based on cigarettes purchased across a
      price range, five derived metrics (Omax, Pmax, breakpoint, intensity, and
      elasticity) can assess cigarette demand. A study with adolescent smokers found
      that these could be reduced to two latent factors: persistence (price
      insensitivity) and amplitude (volumetric consumption). We sought to replicate
      this structure with adult smokers and examine how these variables relate to
      cessation efforts. METHOD: Web-based survey conducted in 2014 among adult (18
      years and above) current daily cigarette smokers (N = 1194). Participants
      completed the CPT, Fagerstrom Test for Nicotine Dependence (FTND), reported past
      year quit attempts, and future quit intentions. We included published scales
      assessing perceived prevalence of smoking, social reactivity, smoker identity,
      and risk perception. RESULTS: Our analysis supported two latent variables,
      persistence and amplitude, which correlated positively with FTND. Persistence was
      correlated with several psychosocial factors and was higher among those intending
      to quit very soon, but did not vary by number of past-year quit attempts.
      Amplitude differed across quit attempts and intention (p < 0.001) and, in
      multivariable models, was significantly associated with lower 30-day quit
      intention (OR = 0.76, p = 0.001). CONCLUSIONS: Persistence and amplitude factors
      characterized CPT data in adults, discriminated known groups (e.g., smokers by
      intentions to quit), and were positively associated with nicotine dependence.
      Factor scores also appear to relate to certain psychosocial factors, such as
      smoker identity and perceptions of risk. Future research should examine the
      predictive validity of these constructs.

PMID- 27048157
TI  - Sex differences in reinstatement of alcohol seeking in response to cues and
      yohimbine in rats with and without a history of adolescent corticosterone
      exposure.
AB  - RATIONALE: Women represent a vulnerable and growing population with respect to
      alcohol abuse. Elevated glucocorticoid exposure in adolescence increases
      addiction risk and stress sensitivity in adulthood. However, little is known
      about sex differences in ethanol craving-like behavior. OBJECTIVE: This study
      characterized sex differences in ethanol-motivated behavior following ethanol
      paired cues and/or acute stimulation of the HPA axis in male and female rats with
      or without exposure to chronically elevated glucocorticoids in adolescence.
      METHODS: Adolescent corticosterone-treated (Experiment 1) or naive (Experiment 2)
      male and female rats were trained as adults to self-administer ethanol paired
      with a cue, and tested for the effects of this cue, alone or in combination with
      yohimbine, on the reinstatement of ethanol seeking. RESULTS: Females showed
      elevated ethanol self-administration and seeking compared to males. In Experiment
      1, corticosterone exposure in adolescence augmented cue-induced reinstatement of
      ethanol seeking in females only, and females were more sensitive to yohimbine in
      promoting reinstatement. Experiment 2 replicated these findings and showed that
      exposure to both yohimbine and alcohol-related cues enhanced the reinstatement of
      alcohol seeking, producing additive effects in females. Corticosterone levels
      were higher in females and in yohimbine-treated rats, and corticosterone and
      estradiol correlated with responding during reinstatement. CONCLUSIONS: Chronic
      manipulations in adolescence and acute manipulations in adulthood of the HPA axis
      increase cue-induced reinstatement of ethanol seeking to a greater degree in
      females than in males. Elucidating the mechanisms that underlie these effects may
      lead to the development of sex-specific interventions aimed at mitigating alcohol
      relapse risk in females.

PMID- 27048158
TI  - Effects of dorsal hippocampal orexin-2 receptor antagonism on the acquisition,
      expression, and extinction of morphine-induced place preference in rats.
AB  - RATIONALE: Orexinergic system is involved in reward processing and drug
      addiction. OBJECTIVES: Here, we investigated the effect of intrahippocampal CA1
      administration of orexin-2 receptor (OX2r) antagonist on the acquisition,
      expression, and extinction of morphine-induced place preference in rats. METHODS:
      Conditioned place preference (CPP) was induced by subcutaneous injection of
      morphine (5 mg/kg) during a 3-day conditioning phase. Three experimental plots
      were designed; TCS OX2 29 as a selective antagonist of orexin-2 receptors (OX2rs)
      was dissolved in DMSO, prepared in solutions with different concentrations (1, 3,
      10, and 30 nM), and was bilaterally microinjected into the CA1 and some
      neighboring regions (0.5 MUl/side). Conditioning scores and locomotor activities
      were recorded during the test. RESULTS: Results demonstrate that intra-CA1
      administration of the OX2r antagonist attenuates the induction of morphine CPP
      during the acquisition and expression phases. Effect of TCS OX2 29 on reduction
      of morphine CPP was dose-dependent and was more pronounced during the acquisition
      than the expression. Furthermore, higher concentrations of TCS OX2 29 facilitated
      the extinction of morphine-induced CPP and reduced extinction latency period.
      Nevertheless, administration of TCS OX2 29 solutions did not have any influence
      on locomotor activity of all phases. CONCLUSIONS: Our findings suggest that OX2rs
      in the CA1 region of hippocampus are involved in the development of the
      acquisition and expression of morphine CPP. Moreover, blockade of OX2rs could
      facilitate extinction and may abrogate or extinguish the ability of drug-related
      cues, implying that the antagonist might be considered as a propitious
      therapeutic agent in suppressing drug-seeking behavior.

PMID- 27048159
TI  - The influence of body composition on the N-terminal pro-B-type natriuretic
      peptide level and its prognostic performance in patients with acute coronary
      syndrome: a cohort study.
AB  - BACKGROUND: Whether body composition is associated with the N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) level and its prognostic performance in acute
      coronary syndrome (ACS) remains unknown. We aimed to investigate the influence of
      body composition on the NT-proBNP level and its prognostic performance among ACS
      patients. METHODS: In total, 1623 ACS patients with NT-proBNP data were enrolled.
      Percent body fat and lean mass index were estimated using the Clinica Universidad
      de Navarra-Body Adiposity Estimator equation. Patients were divided into three
      groups according to the tertiles of sex-specific body mass index, percent body
      fat, or lean mass index. The endpoints were death from any cause and
      cardiovascular death. RESULTS: Body mass index was inversely correlated with NT
      proBNP levels (beta = -0.036, P = 0.003). Lean mass index, but not percent body
      fat, was inversely associated with NT-proBNP levels (beta of lean mass index = 
      0.692, P = 0.002). During a median follow-up of 23 months, 161 all-cause deaths
      occurred, and of these, 93 (57.8 %) were attributed to cardiovascular causes.
      Multivariate Cox analysis showed that the NT-proBNP level independently predicted
      all-cause mortality or cardiovascular death in the lower body mass index, lean
      mass index, and percent body fat groups. However, the prognostic performance of
      NT-proBNP was attenuated in patients with high body mass index, lean mass index,
      and percent body fat. In the subgroup of patients with diabetes, inverse
      associations between NT-proBNP levels and body mass index or body composition
      were not observed. In addition, the negative influence of high body mass index
      and body composition on the prognostic performance of the NT-proBNP level
      appeared to be attenuated. CONCLUSIONS: Body mass index and lean mass index, but
      not percent body fat, are inversely associated with NT-proBNP levels. The
      prognostic performance of this biomarker may be compromised in patients with high
      body mass index, percent body fat, or lean mass index. Additionally, the
      influence of body composition on the NT-proBNP level and its prognostic
      performance might be attenuated in diabetic patients with ACS.

PMID- 27048160
TI  - Management of Benign Prostatic Hyperplasia Larger than 100 ml: Simple Open
      Enucleation Versus Transurethral Laser Prostatectomy.
AB  - Benign prostatic hyperplasia (BPH) is one of the most common causes of lower
      urinary tract symptoms (LUTS) in aging men. Over the age of 60, more than a half
      of men have BPH and/or bothersome LUTS. Contemporary guidelines advocate surgery
      as the standard of care for symptomatic BPH after failure of medical therapy,
      where the choice of the appropriate surgical procedure depends on the prostate
      size. Transurethral resection of the prostate (TURP) and simple open
      prostatectomy (OP) have been considered for decades the reference-standard
      techniques for men with prostate smaller and larger than 80 ml, respectively.
      However, both procedures are potentially associated with considerable
      perioperative morbidity which prompted the introduction of a variety of minimally
      invasive surgical techniques with comparable long-term outcomes compared to TURP
      and OP. Nevertheless, the management of prostates larger than 100 ml remains a
      clinical challenge. Transurethral anatomical enucleation of the prostate
      utilizing different laser energy represents an excellent alternative concept in
      transurethral BPH surgery. These procedures gained popularity and demonstrated
      similar outcomes to OP with the advantages of favorable morbidity profiles and
      shorter catheter time and hospital stay. Despite the fact that OP remains a
      viable treatment option for patients with bothersome LUTS secondary to very large
      prostates, this procedure has been to a large extent replaced by these emerging
      enucleation techniques. Given the advent of surgical alternatives, the current
      review presents an evidence-based comparison of the efficacy and safety profile
      of the currently available transurethral laser techniques with the standard OP
      for the management of BPH due to adenomas larger than 100 ml.

PMID- 27048162
TI  - Biography--Jozsef Timar.

PMID- 27048163
TI  - A retrospective analysis of eye conditions among children attending St. John Eye
      Hospital, Hebron, Palestine.
AB  - BACKGROUND: Eye diseases are important causes of medical consultations, with the
      spectrum varying in different regions. This hospital-based descriptive study
      aimed to determine the profile of childhood eye conditions at St. John tertiary
      Eye hospital serving in Hebron, Palestine. METHODS: Files of all new patients
      less than 16 years old who presented to St. John Eye Hospital-Hebron, Palestine
      between January 2013 and December 2013 were retrospectively reviewed. Age at
      presentation, sex, and clinical diagnosis were extracted from medical records.
      Data were stored and analyzed using Wizard data analysis version 1.6.0 by Evan
      Miller. The Chi square test was used to compare variables and a p value of less
      than 0.05 was considered statistically significant. RESULTS: We evaluated the
      records of 1102 patients, with a female: male ratio of 1:1.1. Patients aged 0-5
      years old were the largest group (40.2%). Refractive errors were the most common
      ocular disorders seen (31.6%), followed by conjunctival diseases (23.7%) and
      strabismus and amblyopia (13.8%). Refractive errors were recorded more frequently
      and statistically significant (p < 0.001) among (11-15) age group. Within the
      conjunctival diseases category, conjunctivitis and dry eyes was more prominent
      and statistically significant (p < 0.001) among the 6-10 year old age group.
      Within the strabismus and amblyopia category, convergent strabismus was more
      common and statistically significant among the youngest age group (0-5 years
      old). CONCLUSIONS: The most common causes of ocular morbidity are largely
      treatable or preventable. These results suggest the need for awareness campaigns
      and early intervention programs.

PMID- 27048161
TI  - Spanish consensus for the management of patients with anaplastic cell thyroid
      carcinoma.
AB  - Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost
      uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish
      Society of Endocrinology and Nutrition and the Grupo Espanol de Enfermedades
      Huerfanas e Infrecuentes of the Spanish Society of Oncology requested that an
      independent task force draft a more comprehensive consensus statement regarding
      ATC. All relevant literature was reviewed, including serial PubMed searches
      together with additional articles. This is the first, comprehensive Spanish
      consensus statement for ATC and includes the characteristics, diagnosis, initial
      evaluation, treatment goals, recommendations and modalities for locoregional and
      advanced disease, palliative care options, surveillance, and long-term
      monitoring. Newer systemic therapies are being investigated, but more effective
      combinations are needed to improve patient outcomes. Though more aggressive
      radiotherapy has reduced locoregional recurrences, median overall survival has
      not improved in more than 50 years.

PMID- 27048164
TI  - Surgery for hyperparathyroidism is associated with reduced fracture risk.

PMID- 27048165
TI  - An Overview on Bacteriophages: A Natural Nanostructured Antibacterial Agent.
AB  - BACKGROUND: Recent advances in the field of bionanomedicine not only enable us to
      produce biomaterials but also to manipulate them at molecular level. Viruses
      particularly bacteriophages are a promising nanomaterial that can be
      functionalized with great precision. Bacteriophages are the natural antimicrobial
      agents that fight against antibiotic resistant bacteria which cause infections in
      animals, humans, or in crops of agricultural value. The idea of utilizing
      bacteriophages as therapeutic agents is due to their ability to kill bacteria at
      the end of the infectious cycle. OBJECTIVE: This paper reviewed the general
      biology of bacteriophages and the presence of receptors on the bacteria which are
      necessary for the recognition and adsorption of bacteriophages. Pharmacokinetics
      and therapeutic potential of bacteriophages administered through various routes
      in treating diverse bacterial infections is also reviewed along with the problems
      associated with bacteriophage therapy. CONCLUSION: Among various routes of
      administration, parenteral route is found to be the most thriving route for the
      treatment of systemic infections whereas oral route is meant to treat
      gastrointestinal infections and; local delivery (skin, nasal, ears) of phages has
      proven its potency to treat topical infections.

PMID- 27048166
TI  - Cash for cutting antibiotic use: a novel initiative that needs to be properly
      thought through.

PMID- 27048168
TI  - Flow-Induced Damage to Blood Cells in Aortic Valve Stenosis.
AB  - Valvular hemolysis and thrombosis are common complications associated with
      stenotic heart valves. This study aims to determine the extent to which
      hemodynamics induce such traumatic events. The viscous shear stress downstream of
      a severely calcified bioprosthetic valve was evaluated via in vitro 2D particle
      image velocimetry measurements. The blood cell membrane response to the measured
      stresses was then quantified using 3D immersed-boundary computational
      simulations. The shear stress level at the boundary layer of the jet flow formed
      downstream of the valve orifice was observed to reach a maximum of 1000-1700
      dyn/cm(2), which was beyond the threshold values reported for platelet activation
      (100-1000 dyn/cm(2)) and within the range of thresholds reported for red blood
      cell (RBC) damage (1000-2000 dyn/cm(2)). Computational simulations demonstrated
      that the resultant tensions at the RBC membrane surface were unlikely to cause
      instant rupture, but likely to lead to membrane plastic failure. The resultant
      tensions at the platelet surface were also calculated and the potential damage
      was discussed. It was concluded that although shear-induced thrombotic trauma is
      very likely in stenotic heart valves, instant hemolysis is unlikely and the shear
      induced damage to RBCs is mostly subhemolytic.

PMID- 27048167
TI  - The new (dis)order in RNA regulation.
AB  - RNA-binding proteins play a key role in the regulation of all aspects of RNA
      metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have
      been thought to be mostly mediated by canonical RNA-binding domains that form
      stable secondary and tertiary structures. However, a number of pioneering studies
      over the past decades, together with recent proteome-wide data, have challenged
      this view, revealing surprising roles for intrinsically disordered protein
      regions in RNA binding. Here, we discuss how disordered protein regions can
      mediate protein-RNA interactions, conceptually grouping these regions into RS
      rich, RG-rich, and other basic sequences, that can mediate both specific and non
      specific interactions with RNA. Disordered regions can also influence RNA
      metabolism through protein aggregation and hydrogel formation. Importantly,
      protein-RNA interactions mediated by disordered regions can influence nearly all
      aspects of co- and post-transcriptional RNA processes and, consequently, their
      disruption can cause disease. Despite growing interest in disordered protein
      regions and their roles in RNA biology, their mechanisms of binding, regulation,
      and physiological consequences remain poorly understood. In the coming years, the
      study of these unorthodox interactions will yield important insights into RNA
      regulation in cellular homeostasis and disease. 

PMID- 27048169
TI  - Primary melanoma tumor inhibits metastasis through alterations in systemic
      hemostasis.
AB  - Progression from a primary tumor to distant metastases requires extensive
      interactions between tumor cells and their microenvironment. The primary tumor is
      not only the source of metastatic cells but also can also modulate host responses
      to these cells, leading to an enhancement or inhibition of metastasis. Tumor
      mediated stimulation of bone marrow can result in pre-metastatic niche formation
      and increased metastasis. However, a primary tumor can also inhibit metastasis
      through concomitant tumor resistance-inhibition of metastatic growth by existing
      tumor mass. Here, we report that the presence of a B16F10 primary tumor
      significantly restricted numbers and sizes of experimental lung metastases
      through reduction of circulating platelets and reduced formation of metastatic
      tumor cell-associated thrombi. Tumor-bearing mice displayed splenomegaly,
      correlated with primary tumor size and platelet count. Reduction in platelet
      numbers in tumor-bearing animals was responsible for metastatic inhibition, as
      restoration of platelet numbers using isolated platelets re-established both
      tumor cell-associated thrombus formation and experimental metastasis. Consumption
      of platelets due to a B16F10 primary tumor is a form of concomitant tumor
      resistance and demonstrates the systemic impact of a growing tumor. Understanding
      the interplay between primary tumors and metastases is essential, as
      clarification of concomitant tumor resistance mechanisms may allow inhibition of
      metastatic growth following tumor resection. Key messages Mice with a primary
      B16F10 tumor had reduced metastasis vs. mice without a primary tumor. Tumor
      bearing mice had splenomegaly and fewer platelets and tumor-associated thrombi.
      Restoring platelets restored tumor-associated thrombi and increased metastasis.
      This work shows the impact that a primary tumor can have on systemic metastasis.
      Understanding these interactions may lead to improved ways to inhibit metastasis.

PMID- 27048171
TI  - Description of the First Species of Trieces (Hymenoptera: Ichneumonidae) with
      Tyloids in the Male Antennae and New Records of Neotropical Species.
AB  - A new species of Trieces Townes from Brazil, Trieces tyloidalis n. sp., is
      described and illustrated. This is the first known species of Trieces with
      tyloids in the male antennae. The genus is recorded from Belize, Ecuador and
      Venezuela for the first time. Trieces horisme Gauld & Sithole, Trieces platysoma
      Townes, Trieces riodinis Gauld & Sithole and Trieces tuvule Gauld & Sithole, are
      recorded for the first time from several South American countries. A key to
      twelve South American species of Trieces is provided. 

PMID- 27048170
TI  - Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with
      a protofibril selective Abeta antibody.
AB  - BACKGROUND: Several monoclonal antibodies for the treatment of Alzheimer's
      disease (AD) have been in development over the last decade. BAN2401 is a
      monoclonal antibody that selectively binds soluble amyloid beta (Abeta)
      protofibrils. METHODS: Here we describe the first clinical study with BAN2401.
      Safety and tolerability were investigated in mild to moderate AD. A study design
      was used with staggered parallel single and multiple ascending doses, from 0.1
      mg/kg as a single dose to 10 mg/kg biweekly for four months. The presence of
      amyloid related imaging abnormalities (ARIA, E for edema, H for hemorrhage) was
      assessed with magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) and
      plasma samples were analyzed to investigate pharmacokinetics (PK) and effects on
      biomarkers. RESULTS: The incidence of ARIA-E/H on MRI was comparable to that of
      placebo. BAN2401 exposure was approximately dose proportional, with a serum
      terminal elimination half-life of ~7 days. Only a slight increase of plasma
      Abeta(1-40) was observed but there were no measurable effects of BAN2401 on CSF
      biomarkers. On the basis of these findings Phase 2b efficacy study has been
      initiated in early AD. CONCLUSIONS: BAN2401 was well-tolerated across all doses.
      The PK profile has guided us for selecting dose and dose regimens in the ongoing
      phase 2b study. There was no clear guidance for an effective dose based on
      biomarkers. TRIAL REGISTRATION NUMBER: NCT01230853 ClinicalTrials.gov Registered
      October 27, 2010.

PMID- 27048172
TI  - Parasitism Performance of Tetrastichus brontispae Ferriere over the Coconut
      Hispine Beetle, Brontispa longissima (Gestro).
AB  - In this study, the effect of host density, host, and parasitoid ages in choice
      and no-choice tests on the parasitism performance of Tetrastichus brontispae
      Ferriere, one of the major parasitoid of Brontispa longissima (Gestro), was
      investigated in the laboratory. The results revealed that an increased host
      density resulted in no increased parasitism of B. longissima by T. brontispae;
      the optimal host density was three host pupae per parasitoid when considering the
      costs for mass rearing. Moreover, parasitoid age was quite crucial for effective
      parasitism and affected the emergence rate. Although 2-h to 4-day-old parasitoids
      successfully parasitized the host pupae, younger parasitoids (within 2-day-old)
      presented higher parasitism capacity than older parasitoids. More importantly,
      both choice and no-choice tests confirmed that all host stages tested from 2-h to
      4-day-old were suitable for T. brontispae parasitization, although 2-h to 2-day
      old hosts were preferred. We also demonstrated that sex ratio, emergence rate,
      and egg to adult developmental time were not influenced by host density,
      parasitoid, and host age in both choice and no-choice tests. Our data will allow
      for more accurate prediction and interpretation on the parasitization by T.
      brontispae, supporting mass-production initiatives and mass release in programs
      of B. longissima. 

PMID- 27048173
TI  - Changes in seroprevalence of hepatitis B surface antigen and epidemiologic
      characteristics in the Republic of Korea, 1998-2013.
AB  - OBJECTIVES: This study investigated changes in hepatitis B seroprevalence from
      1998 to 2013, and to identify differences in epidemiologic characteristics
      between hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative people.
      METHODS: HBsAg seropositive rates were compared by year, sex, and age using the
      blood test data from the periods I to VI (1998-2013) of the Korea National Health
      and Nutrition Examination Survey. Interviews and self-administered surveys were
      conducted to collect data on health behavior, quality of life, comorbidities, and
      health care utilization. RESULTS: HBsAg seropositive rates in the Republic of
      Korea decreased from 4.6% in 1998 to 2.9% in 2008, and then remained the same for
      the next five years. While seropositive rates by age were the highest at 35 to 39
      years of age in 1998, it peaked at 50 to 54 years of age in 2013. HBsAg-positive
      people showed high values from two liver function tests, including glutamic
      oxaloacetic transaminase and glutamic-pyruvic transaminase, and the prevalence
      rates of liver cirrhosis and liver cancer were also significantly high. Indices
      for health behavior and quality of life showed no significant differences between
      HBsAg-positive and HBsAg-negative people. CONCLUSIONS: While HBsAg seropositive
      rates tended to decline after 1998, there have been no significant changes over
      the most recent five years. We should focus on treatment of existing hepatitis B
      patients along with immunization programmes to prevent new hepatitis B
      infections. In addition, it may be necessary to encourage HBsAg-positive people
      to follow healthier life-styles in order to prevent further progression of
      hepatitis B to liver cirrhosis and liver cancer.

PMID- 27048174
TI  - Erratum to: Development and application of lateral flow test strip technology for
      detection of infectious agents and chemical contaminants: a review.

PMID- 27048175
TI  - Snoring as a Determinant Factor of Oxidative Stress in the Airway of Patients
      with Obstructive Sleep Apnea.
AB  - PURPOSE: In obstructive sleep apnea-hypopnea syndrome (OSAS), airway collapses
      and vibrations cause local and systemic inflammatory response and oxidative
      stress (OS). Our objective was to determine the presence of OS in the airway of
      patients with OSAS compared with controls without OSAS and determine its relation
      to treatment with CPAP and other clinical variables. METHOD: We performed a
      prospective observational case-control study with repeated measures. We recruited
      consecutive patients with SAHS diagnosed using complete polysomnography, and a
      parallel control group. We collected a sample of exhaled breath condensate (EBC)
      prior to nasal continuous positive airway pressure (CPAP) treatment and again
      after 4 months. The marker of OS used was 8-isoprostane (8-IPN). The variables
      analyzed were age, sex, anthropometric variables, apnea-hypopnea index (AHI),
      snoring, oxygenation, and polysomnographic variables. RESULTS: The study included
      20 patients and 10 controls. In cases, the initial value of 8-IPN was 6.8 (1.9),
      and after nasal CPAP, it was 5.3 (1.2) pg/ml (p = 0.02). In controls, the value
      of 8-IPN was 5.6 (1.1) pg/ml (p = 0.04 compared to initial values). 8-IPN showed
      significant correlation with snoring, AHI, BMI, nocturnal desaturation index, and
      non-REM sleep. On multivariate analysis, only snoring was a significant predictor
      of 8-IPN. CONCLUSIONS: Snoring, and not OSAS severity, could be the phenomenon
      underlying the presence of local OS measured in the airway of patients with OSAS.

PMID- 27048176
TI  - Dental-macrowear and diet of Tigara foragers from Point Hope, northern Alaska.
AB  - SUMMARY: Ethnographic studies indicate that Eskimo foragers are characterized by
      well-defined sexual division of labor and extensive use of anterior teeth as a
      tool, resulting in higher degrees of wear. However, little is known about the
      intra-population variation in molar-macrowear rates and dietary implications.
      Here, percentages of dentin exposure (PDE) were recorded on first mandibular
      molars among Tigara foragers from Point Hope (Alaska) and attempt to correlate
      age and sex variation in wear patterns. We found that no overall sex-related
      differences in PDE exist and suggest that molars did not take a part in para
      masticatory or cultural practices. Strong correlation with increasing age was
      found as expected but males wore their teeth at higher rates than females related
      to masticatory demands during growth. Our findings suggest that individual
      variation in molar-macrowear must be attributed to biomechanics of chewing and
      cultural behavior rather than sexual variation in food acquisition.

PMID- 27048177
TI  - Mitotic spindle formation in Triparma laevis NIES-2565(Parmales,
      Heterokontophyta).
AB  - The parmalean algae possess a siliceous wall and represent the sister lineage of
      diatoms; they are thought to be a key group for understanding the evolution of
      diatoms. Diatoms possess well-characterized and unique mitotic structures, but
      the mitotic apparatus of Parmales is still unknown. We observed the microtubule
      (MT) array during interphase and mitosis in Triparma laevis using TEM. The
      interphase cells had four or five centrioles (~80 nm in length), from which MTs
      emanated toward the cytoplasm. In prophase, the bundle of MTs arose at an
      extranuclear site. The position of centrioles with respect to an MT bundle
      changed during its elongation. Centrioles were observed on the lateral side of a
      shorter MT bundle (~590 nm) and on either side of an extended MT bundle (~700
      nm). In metaphase, the spindle consisted of two types of MTs-MT bundle that
      passed through a cytoplasmic tunnel in the center of the nucleus and single MTs
      (possibly kinetochore MTs) that extended from the poles into the nucleus. The
      nuclear envelope disappeared only at the regions where the kinetochore MTs
      penetrated. In telophase, daughter chromosomes migrated toward opposite poles,
      and the MT bundle was observed between segregating chromosomes. These
      observations showed that MT nucleation does not always occur at the periphery of
      centrioles through cell cycle and that the spindle of T. laevis has a similar
      configuration to that of diatoms.

PMID- 27048179
TI  - The role of enhanced depth imaging optical coherence tomography in chronic Vogt
      Koyanagi-Harada disease.
AB  - AIMS: To determine the role of enhanced depth imaging optical coherence
      tomography (EDI-OCT) in chronic Vogt-Koyanagi-Harada (VKH) disease. METHODS:
      Records of all consecutive patients with VKH seen at the Singapore National Eye
      Centre were retrospectively reviewed for concurrent EDI-OCT and indocyanine green
      angiograms (ICGAs) obtained six or more months after disease onset, demographics
      and duration of disease. The ICGAs were scored based on the following signs:
      early choroidal stromal vessel hyperfluorescence and leakage, hypofluorescent
      dark dots, fuzzy vascular pattern of large stromal vessels and disc
      hyperfluorescence, and correlated with the subfoveal choroidal thickness (SFCT)
      measured using EDI-OCT. Only images of one eye were analysed. RESULTS: 105 pairs
      of EDI-OCT and ICGA of 52 patients were included. Mean age was 51.7 years. Half
      of the patients (26) were male and the majority were Chinese (39 patients,
      75.0%). Mean duration of disease was 106.3 months. There were 79 ICGA active
      episodes. Mean SFCT was thinner when ICGA was quiet (mean=187.31 MU), than when
      the ICGA was active (mean=272.38 MU, p=0.002). There was a positive correlation
      of the SFCT with the ICGA score but a negative correlation with age and duration
      of disease. Multivariate analysis showed that age, duration of disease and ICGA
      were the main factors affecting SFCT. CONCLUSIONS: The positive correlation of
      SFCT measurements with ICGA score suggests that it may be used to monitor disease
      activity in chronic VKH in addition to ICGA, possibly reducing the number of
      ICGAs required.

PMID- 27048178
TI  - Female gametophyte and embryo development in Helleborus bocconei Ten.
      (Ranunculaceae).
AB  - In this study, we investigated cytohistochemistry, cycle progression, and
      relative DNA content of the female gametophyte cells of Helleborus bocconei Ten.
      before and after fertilization process. The early stages of embryo development
      were also investigated. H. bocconei possesses a monosporic seven-celled/eight
      nucleate Polygonum type female gametophyte, characterized by a morpho-functional
      polarity. The cells of the embryo sac showed abundant reserves of
      polysaccharides, strongly increasing in the egg cell just before fertilization.
      With different timing in DNA replication during cell cycle progression,
      synergids, egg cells, and polar nuclei showed a haploid DNA content at the end of
      their differentiation, while antipodes underwent three DNA endoreduplication
      cycles. Programmed cell death symptoms were detectable in synergid and antipodal
      cells. After double fertilization, the central cell quickly underwent many
      mitotic cycles forming the endosperm, which exhibited a progressive increase in
      protein bodies and starch grains. Close to the developing embryo, the endosperm
      differentiated a well-defined region rich in a fibrillar carbohydrate matrix. The
      zygote, that does not start immediately to divide after double fertilization,
      developed in to an embryo that reached the heart stage at fruit maturation time.
      A weakly differentiated embryo at this time indicates a morpho-physiological
      dormancy of seeds, as a survival strategy imposed by the life cycle of this plant
      with seed dispersal in spring and their germination in the following winter.

PMID- 27048180
TI  - A Metastatic Squamous Cell Carcinoma in a Diabetic Foot: Case Report.
AB  - A 72-year-old male was referred to our hospital for a plantar ulceration that had
      occurred many years earlier. The lesion, with exuberant granulation and large
      areas of necrosis and fibrin, had long been treated by plastic surgeons with no
      positive evolution. At admission in our hospital no ischemia was detected, and
      foot radiograph was negative for bone involvement. The patient underwent a foot
      magnetic resonance imaging, which showed high vascularization in the plantar
      region and early capture of the contrast medium. We then performed multiple
      biopsies of the ulceration that revealed a moderately differentiated squamous
      cell carcinoma. The total body computed tomography exam raised a systemic
      involvement. A lymph node biopsy and immunohistochemistry assay on the pleural
      cytological sample proved the presence of a primary squamous cell carcinoma of
      the foot with systemic dissemination. Although rare, squamous cell carcinoma
      could be associated with chronic nonhealing ulcers; therefore, when a lesion does
      not heal, despite adequate standard treatment, its etiopathogenesis should be
      challenged. 

PMID- 27048181
TI  - Drug-metabolizing Enzymes and Efflux Transporters in Nasal Epithelium: Influence
      on the Bioavailability of Intranasally Administered Drugs.
AB  - BACKGROUND: The interest in administering drugs by intranasal route is currently
      increasing, particularly because it has shown to ensure drug therapeutic action
      by a rapid systemic absorption through the respiratory mucosa and/or a direct
      delivery of some molecules into the brain through the olfactory mucosa.
      Nevertheless, although intranasal administration avoids the first-pass hepatic
      biotransformation, several enzymes as well as efflux transporters can be found in
      the mammalian nasal epithelium. METHODS: This work reviewed the expression and
      localization of the drug-metabolizing enzymes and efflux transporters in the
      mammalian nasal mucosa epithelium, as well as their influence on the
      pharmacokinetic and pharmacodynamic profiles of specific drugs, using one hundred
      and thirty five peer-reviewed papers undertaken from MEDLINE database, including
      review and research papers. RESULTS: Most of the studies analyzed corroborate
      that oxidative and conjugative enzymes as well as multidrug resistance proteins
      and multidrug resistance-associated proteins efflux transporters are expressed in
      the nasal cavity, particularly in olfactory and respiratory mucosae, determining
      the access of drugs to central nervous system and bloodstream. Nonetheless,
      besides their well-documented anatomic location, either in laboratory animals or
      humans, there is still a lack of experimental information regarding the
      substrates of these enzymes and efflux transporters at the nasal cavity.
      CONCLUSION: The knowledge herein discussed important not only to select the drugs
      with better potential to be administered by intranasal route but also to optimize
      drug formulations, in which inhibitors of enzymes or efflux transporters may be
      included to increase drug systemic and central delivery.

PMID- 27048182
TI  - Medication-Induced Nephrotoxicity in Older Patients.
AB  - OBJECTIVE: To summarize current evidence about mechanisms, clinical features,
      diagnostic issues, and strategies for prevention of medication-induced
      nephrotoxicity among older people. METHODS: A Pubmed search was performed, and
      studies concerning age-related changes in kidney structure and function
      predisposing to nephrotoxicity, pathophysiological mechanisms, kidney drug
      metabolism enzymes, clinical epidemiology of medication-induced kidney damage,
      biomarkers for early identification of nephrotoxicity and strategies for
      prevention of medication-induced nephrotoxicity among older people were selected.
      Finally, 245 papers were included in the review. RESULTS: Medications may induce
      nephrotoxicity through several pathophysiological mechanisms. People aged 75 or
      more are especially exposed to potential nephrotoxic medications or combinations
      of medications in the context of complex polypharmacy regimens. Estimated
      glomerular filtration rate (eGFR) may be useful to identify medication-induced
      alterations in kidney function, but creatinine-based methods have important
      limitation in older patients. Several innovative biomarkers have been proposed to
      identify AKI but these methodologies are not standardized and older people have
      not been evaluated systematically. Factors related to patient, medication, and
      interactions should be taken into account for effective prevention. CONCLUSIONS:
      Medication-induced nephrotoxicity is a relevant problem in older populations.
      Nevertheless, several areas of uncertainty remain to be explored, including the
      impact of nephrotoxicity on functional outcomes relevant to older patients, the
      reliability of currently recommended methods for diagnosing and staging AKI, the
      use of innovative biomarkers in such a heterogeneous population, the
      effectiveness of preventing strategies and treatments and their impact on
      functional outcomes.

PMID- 27048183
TI  - Living in areas with good public transport links can increase physical activity
      by 90 minutes a week.

PMID- 27048187
TI  - Asthma as a Comorbidity in Hospitalized Patients: A Potential Missed Opportunity
      to Intervene.
AB  - Asthma is a frequent comorbidity in hospitalized children and adults. Patients
      with a history of asthma may have no breathing complaints or abnormal chest exam
      findings to trigger care for this comorbidity during hospitalization.
      Consequently, this may lead to a potential missed opportunity to discuss asthma
      as a comorbidity and ongoing issue to ensure its optimal management at home. Our
      goal is to raise awareness that such patient encounters may represent
      opportunities for health care professionals to optimize asthma management.
      Despite focusing on the present illness and limited time availability, asthma
      care may be improved in a time-efficient manner in these patients.

PMID- 27048188
TI  - Evaluation of Sodium Polystyrene Sulfonate Dosing Strategies in the Inpatient
      Management of Hyperkalemia.
AB  - BACKGROUND: Hyperkalemia occurs frequently in an inpatient setting, for which
      sodium polystyrene sulfonate (SPS) is a common treatment modality. Few studies
      have investigated the dose-response of SPS. OBJECTIVE: To quantify the change in
      serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS.
      Secondary objectives were to compare the proportion of patients attaining post
      SPS dose normokalemia between dosing groups and to investigate the effect of
      certain characteristics on SPS dose-response. METHODS: The reduction in serum
      potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS administered
      to adult inpatients was evaluated through a retrospective chart review. Ottawa
      Hospital Research Ethics Board approval was obtained prior to data collection.
      RESULTS: A total of 118 patients were included in the analysis. Serum potassium
      levels were reduced by 0.39, 0.69, 0.91, and 0.22 mEq/L following 15-, 30-, and
      60-g oral doses and a 30-g rectal dose of SPS, respectively. A greater proportion
      of patients (50% vs 23%) remained hyperkalemic in the 15-g versus the 60-g group
      (P = 0.018), and all patients in the rectal group remained hyperkalemic. No
      patient in any group experienced postdose hypokalemia. The influence of all
      studied interindividual characteristics on SPS dose-response was clinically
      nonsignificant. CONCLUSION: Mild hyperkalemia can be effectively treated with a
      single 60-g oral dose of SPS as monotherapy, with minimal risk of hypokalemia.
      Moderate to severe hyperkalemic episodes warrant alternative therapy. The
      potassium-lowering effect is correlated to SPS dose and is independent of
      interindividual characteristics.

PMID- 27048184
TI  - Statins and Aspirin use in HIV-infected people: gap between European AIDS
      Clinical Society guidelines and clinical practice: the results from HIV-HY study.
AB  - OBJECTIVES: To investigate the use of statins and acetylsalicylic acid (ASA) in
      HIV people in clinical practice. DESIGN: A multicenter, nationwide, prospective
      cohort study, including 1182 consecutive HIV patients was conducted. METHODS:
      Statin and ASA prescription was evaluated in primary and secondary cardiovascular
      disease prevention, according to the European AIDS Clinical Society (EACS)
      guidelines. RESULTS: Followed-up patients (998) were mostly males (70.9 %) with a
      mean age at enrolment of 46.5 years (SD 9.5). The mean time of follow-up was 3.3
      years (SD 0.8). At the last follow-up visit, statins would have been recommended
      for 31.2 % and ASA for 16 % by EACS guidelines. Conversely, only 15.6 and 7.6 %
      of patients were on statin and ASA treatment, respectively; only 50.3 % of
      patients treated with statins achieved recommended low-density lipoprotein
      cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin
      therapy and EACS recommendation was 0.58 (95 % CI 0.52-0.63). The corresponding
      figure for ASA therapy was 0.50 (95 % CI 0.42-0.58), whereas the agreement for
      ASA therapy in secondary prevention was 0.59 (95 % CI 0.50-0.68). CONCLUSIONS:
      The prescription of statins and ASA in HIV-infected patients remains largely
      suboptimal, as only about 50 % of patients requiring statins and ASA are properly
      treated. Higher attention on this relevant issue and further investigation are
      warranted in this at risk population.

PMID- 27048189
TI  - Localized Bullous Eruption Away From Injection Site, Caused by Intramuscular
      Meglumine Antimoniate Administration.

PMID- 27048192
TI  - Generalized Intense Pruritus During Canagliflozin Treatment: Is it an Adverse
      Drug Reaction?
AB  - BACKGROUND: Selective agents able to locate and identify unique targets represent
      a crucial aspect of modern pharmacology. The exclusive location of Sodium-Glucose
      co-Transporter-2 (SGLUT2) on kidneys prompt companies to develop SGLT2 inhibitors
      that today are the latest class of drugs for diabetes treatment. In particular,
      canagliflozin blocks the re-absorption of glucose in the kidney lowering blood
      glucose levels by increasing glucose excretion. CASE DESCRIPTION: We report a 61
      year old woman who developed an intense and severe pruritus during the treatment
      with canagliflozin. Clinical and laboratory findings excluded the presence of
      systemic or skin diseases able to induce pruritus. The discontinuation of
      canagliflozin and the treatment with pioglitazone/metformin fixed combination
      induced a remission of pruritus. CONCLUSION: This case emphasizes the need to
      consider pruritus as a differential diagnosis during the treatment with
      canagliflozin.

PMID- 27048190
TI  - Large-Scale Fluorescence Calcium-Imaging Methods for Studies of Long-Term Memory
      in Behaving Mammals.
AB  - During long-term memory formation, cellular and molecular processes reshape how
      individual neurons respond to specific patterns of synaptic input. It remains
      poorly understood how such changes impact information processing across networks
      of mammalian neurons. To observe how networks encode, store, and retrieve
      information, neuroscientists must track the dynamics of large ensembles of
      individual cells in behaving animals, over timescales commensurate with long-term
      memory. Fluorescence Ca(2+)-imaging techniques can monitor hundreds of neurons in
      behaving mice, opening exciting avenues for studies of learning and memory at the
      network level. Genetically encoded Ca(2+) indicators allow neurons to be targeted
      by genetic type or connectivity. Chronic animal preparations permit repeated
      imaging of neural Ca(2+) dynamics over multiple weeks. Together, these
      capabilities should enable unprecedented analyses of how ensemble neural codes
      evolve throughout memory processing and provide new insights into how memories
      are organized in the brain.

PMID- 27048193
TI  - Triamcinolone Acetonide and Bevacizumab Induced Raised Intraocular Pressure in An
      Elderly Male Diabetic Patient - A Case Report.
AB  - Intravitreal triamcinolone and bevacizumab are emerging treatment modalities for
      the patients of macular oedema; however, they are known to raise intraocular
      pressure. A 61 year old diabetic male patient developed glaucoma after
      administration of triamcinolone acetonide and bevacizumab intravitreally for
      treatment of macular oedema. His intraocular pressure was raised up to about 42
      mm Hg. Such high and sustained rise in intraocular pressure may lead to vision
      loss by damaging the optic nerve. The patient was managed by local as well as
      systematic therapy and was recovered after 1 month from the occurrence of an
      event. Intraocular pressure should be monitored in patients receiving
      intravitreal triamcinolone and bevacizumab. Risk benefit analysis must be done
      before using IVTA and IVB in patients with diabetic macular oedema. 

PMID- 27048194
TI  - Erratum to: World Health Organization Guidelines for Feeding Low Birth Weight
      Infants: Effects of Implementation in First Referral Level Health Facilities in
      India : Investigators of WHO LBW Feeding Study Group, Delhi, India.

PMID- 27048191
TI  - The Adult Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB)
      Neurogenesis.
AB  - A large population of neural stem/precursor cells (NSCs) persists in the
      ventricular-subventricular zone (V-SVZ) located in the walls of the lateral brain
      ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long
      distance into the olfactory bulb (OB) where they differentiate into local circuit
      interneurons. Here, we review a broad range of discoveries that have emerged from
      studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a
      subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of
      neuronal migration, and molecular regulators of precursor cell proliferation and
      migration. It has also become evident that V-SVZ NSCs are regionally
      heterogeneous, with NSCs located in different regions of the ventricle wall
      generating distinct OB interneuron subtypes. Insights into the developmental
      origins and molecular mechanisms that underlie the regional specification of V
      SVZ NSCs have also begun to emerge. Other recent studies have revealed new cell
      intrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ.
      Finally, we discuss intriguing differences between the rodent V-SVZ and the
      corresponding human brain region. The rapidly expanding cellular and molecular
      knowledge of V-SVZ NSC biology provides key insights into postnatal neural
      development, the origin of brain tumors, and may inform the development
      regenerative therapies from cultured and endogenous human neural precursors. 

PMID- 27048195
TI  - Enteric Fever Presenting as Hemorrhagic Shock due to Bleeding from Dieulafoy's
      Lesion.
AB  - Dieulafoy's lesion (DL) is an arteriole that protrudes through a tiny mucosal
      defect, usually within 6 cm of the gastroesophageal junction on the lesser curve
      of the stomach. Similar lesions have also been described in the distal esophagus,
      small intestine, colon, and rectum. Enteric fever has been reported as one of the
      cause of bleeding from DL of ileum in the past. The authors report a rare case of
      life threatening bleeding from DL of stomach in a child with enteric fever. 

PMID- 27048196
TI  - Per cent emphysema is associated with respiratory and lung cancer mortality in
      the general population: a cohort study.
AB  - BACKGROUND: Emphysema on CT is a risk factor for all-cause mortality in persons
      with and without airflow obstruction; however, causes of death associated with
      emphysema remain uncertain, particularly in the general population. AIMS: To test
      associations between quantitatively assessed emphysema on CT and cause of death
      in persons with and without a substantial smoking history. METHODS: The Multi
      Ethnic Study of Atherosclerosis recruited 6814 participants, aged 45-84 years and
      without clinical cardiovascular disease, in 2000-2002. Per cent emphysema was
      defined on cardiac CT as per cent of lung voxels less than -950 Hounsfield units;
      emphysema on CT was defined as per cent emphysema above the upper limit of
      normal. Cause of death was classified by administrative codes. Proportional
      hazards models were adjusted for age, race/ethnicity, gender, body mass index,
      smoking status, pack-years, coronary artery calcium, site and education.
      Additional adjustment for lung function was made in a subset with spirometry from
      2004 to 2006. RESULTS: There were 1091 deaths over 12 years median follow-up.
      Emphysema on CT was strongly associated with increased mortality due to
      respiratory diseases (adjusted HR 2.94, 95% CI 1.68 to 5.15), particularly
      chronic lower respiratory diseases (adjusted HR 9.54, 95% CI 4.70 to 19.35), and
      lung cancer (adjusted HR 1.84, 95% CI 1.09 to 3.12), but not cardiovascular
      disease. Associations persisted among participants with fewer than 10 pack-years
      and those without physician-diagnosed respiratory disease, and were similar after
      adjustment for airflow measures and in persons without airflow limitation.
      CONCLUSIONS: Quantitatively assessed emphysema on CT is associated with greater
      respiratory disease and lung cancer mortality, even among persons without
      traditional risk factors.

PMID- 27048197
TI  - Cost-effectiveness of FENO-based and web-based monitoring in paediatric asthma
      management: a randomised controlled trial.
AB  - BACKGROUND: In children with asthma, web-based monitoring and inflammation-driven
      therapy may lead to improved asthma control and reduction in medications.
      However, the cost-effectiveness of these monitoring strategies is yet unknown.
      OBJECTIVE: We assessed the cost-effectiveness of web-based monthly monitoring and
      of 4-monthly monitoring of FENO as compared with standard care. METHODS: An
      economic evaluation was performed alongside a randomised controlled multicentre
      trial with a 1-year follow-up. Two hundred and seventy-two children with asthma,
      aged 4-18 years, were randomised to one of three strategies. In standard care,
      treatment was adapted according to Asthma Control Test (ACT) at 4-monthly visits,
      in the web-based strategy also according to web-ACT at 1 month intervals, and in
      the FENO-based strategy according to ACT and FENO at 4-monthly visits. Outcome
      measures were patient utilities, healthcare costs, societal costs and incremental
      cost per quality-adjusted life year (QALY) gained. RESULTS: No statistically
      significant differences were found in QALYs and costs between the three
      strategies. The web-based strategy had 77% chance of being most cost-effective
      from a healthcare perspective at a willingness to pay a generally accepted ?40
      000/QALY. The FENO-based strategy had 83% chance of being most cost-effective at
      ?40 000/QALY from a societal perspective. CONCLUSIONS: Economically, web-based
      monitoring was preferred from a healthcare perspective, while the FENO-based
      strategy was preferred from a societal perspective, although in QALYs and costs
      no statistically significant changes were found as compared with standard care.
      As clinical outcomes also favoured the web-based and FENO-based strategies, these
      strategies may be useful additions to standard care. TRIAL REGISTRATION NUMBER:
      Netherlands Trial Register (NTR1995).

PMID- 27048198
TI  - Thorax protocol review: working with trialists to improve trial quality.

PMID- 27048199
TI  - Patient Perspectives on Fecal Microbiota Transplantation for Clostridium
      Difficile Infection.
AB  - INTRODUCTION: Clostridium difficile infection (CDI) is a severe and increasingly
      frequent healthcare-associated infection that develops after disruption of the
      gut microbiota. Immunocompromised, hospitalized patients have an increased
      likelihood of acquiring CDI, leading to lengthened hospital stays, increased
      medical fees, and higher rates of morbidity and mortality. Treatment of CDI is
      challenging because of limited treatment options and a 19-20% recurrence rate.
      Thus, there is a need for effective, affordable and safe treatments for CDI.
      Fecal microbiota transplantation (FMT) is the transplantation of donor stool into
      the intestine of a CDI patient to restore the structure and function of the gut
      microbiota and eradicate CDI. Recently, FMT has become an attractive alternative
      treatment for CDI due to its overwhelming success rate. However, the patient
      perspective on the effect of CDI and the role of FMT in that context is lacking.
      METHODS: We undertook a patient survey to gather qualitative and quantitative
      data on the short-term social, physical, emotional outcomes for patients with CDI
      who have undergone FMT. RESULTS: We found in all patients interviewed that the
      social implications of CDI were generally more severe than the emotional and
      physical aspects. CONCLUSION: Future studies should consider evaluating these
      important patient-centered factors as outcomes. Moreover, patients are willing to
      undergo FMT as treatment for CDI.

PMID- 27048200
TI  - DFT studies on the structural and vibrational properties of polyenes.
AB  - Detailed density functional theory (DFT) calculations on the structure and
      harmonic frequencies of model all-trans and all-cis polyenes were undertaken. For
      the first time, we report on the convergence of selected B3LYP/6-311++G** and
      BLYP/6-311++G** calculated structural parameters resulting from a systematic
      increase in polyene size (chains containing 2 to 14 C = C units). The limiting
      values of the structural parameters for very long chains were estimated using
      simple three-parameter empirical formulae. BLYP/6-311++G** calculated nu(C = C)
      and nu(C-C) frequencies for all-trans and all-cis polyenes containing up to 14
      carbon-carbon double bonds were used to estimate these values for very long
      chains. Correction of raw, unscaled vibrational data was performed by comparing
      theoretical and experimental wavenumbers for polyenes chains containing 3 to 12
      conjugated C = C units with both ends substituted by tert-butyl groups. The
      corrected nu(C = C) and nu(C-C) wavenumbers for all-trans molecules were used to
      estimate the presence of 9 - 12 C = C units in all-trans polyene pigment in red
      coral.

PMID- 27048201
TI  - Population pharmacokinetics and probability of target attainment of meropenem in
      critically ill patients.
AB  - PURPOSE: Patients admitted to intensive care unit (ICU) with Klebsiella
      pneumoniae infections are characterized by high mortality. The aims of the
      present study were to investigate the population pharmacokinetics parameters and
      to assess the probability of target attainment of meropenem in critically ill
      patients to provide information for more effective regimens. METHODS: Twenty
      seven consecutive patients were included in the study. Meropenem was administered
      as 3-h intravenous (i.v.) infusions at doses of 1-2 g every 8 or 12 h. Meropenem
      plasma concentrations were measured by a high-performance liquid chromatography
      (HPLC) method, and a population pharmacokinetics analysis was performed using
      NONMEM software. Meropenem plasma disposition was simulated for extended (3 h; 5
      h) or continuous i.v. infusions, and the following parameters were calculated:
      time during which free drug concentrations were above minimum inhibitory
      concentration (MIC) (fT > MIC), free minimum plasma concentrations above 4* MIC
      (fCmin > 4* MIC), probability of target attainment (PTA), and cumulative fraction
      of response (CFR). RESULTS: Gender and severity of sepsis affected meropenem
      clearance, whose typical population values ranged from 6.22 up to 12.04 L/h (mean
      +/- standard deviation (SD) value, 9.38 +/- 4.47 L/h). Mean C min value was 7.90
      +/- 7.91 mg/L, suggesting a high interindividual variability. The simulation
      confirmed that 88 and 97.5 % of patients achieved effective C min > 4* MIC values
      after 3- and 5-h i.v. infusions of meropenem 2 g * 3/day, respectively. On the
      contrary, the same total daily doses reached the target C min > 4* MIC values in
      100 % of patients when administered as continuous i.v. infusions. CONCLUSIONS:
      Several factors may influence meropenem pharmacokinetics in ICU patients.
      Continuous i.v. infusions of meropenem seem to be more effective than standard
      regimens to achieve optimal therapeutic targets.

PMID- 27048202
TI  - How to apply case reports in clinical practice using surrogate models via example
      of the trigeminocardiac reflex.
AB  - Case reports are an increasing source of evidence in clinical medicine. Until a
      few years ago, such case reports were emerged into systematic reviews and
      nowadays they are often fitted to the development of clinical (thinking) models.
      We describe this modern progress of knowledge creation by the example of the
      trigeminocardiac reflex that was first described in 1999 by a case series and was
      developed over the cause-and-effect relationship, triangulation to systematic
      reviews and finally to thinking models. Therefore, this editorial not only
      underlines the increasing and outstanding importance of (unique) case reports in
      current science, but also in current clinical decision-making and therefore also
      that of specific journals like the Journal of Medical Case Reports. 

PMID- 27048203
TI  - Lack of functional P2X7 receptor aggravates brain edema development after middle
      cerebral artery occlusion.
AB  - Effective therapeutic measures against the development of brain edema, a life
      threatening complication of cerebral ischemia, are necessary to improve the
      functional outcome for the patient. Here, we identified a beneficial role of
      purinergic receptor P2X7 activation in acute ischemic stroke. Involvement of P2X7
      in the development of neurological deficits, infarct size, brain edema, and glial
      responses after ischemic cerebral infarction has been analyzed. Neurologic
      evaluation, magnetic resonance imaging, and immunofluorescence assays were used
      to characterize the receptor's effect on the disease progress during 72 h after
      transient middle cerebral artery occlusion (tMCAO). Sham-operated animals were
      included in all experiments for control purposes. We found P2X7-deficient mice to
      develop a more prominent brain edema with a trend towards more severe
      neurological deficits 24 h after tMCAO. Infarct sizes, T2 times, and apparent
      diffusion coefficients did not differ significantly between wild-type and P2X7(-/
      ) animals. Our results show a characteristic spatial distribution of reactive
      glia cells with strongly attenuated microglia activation in P2X7(-/-) mice 72 h
      after tMCAO. Our data indicate that P2X7 exerts a role in limiting the early
      edema formation, possibly by modulating glial responses, and supports later
      microglia activation.

PMID- 27048204
TI  - Australian paediatric guidelines already acknowledge hypoglycaemia as an
      indicator of good diabetes care.

PMID- 27048205
TI  - Phantom smoking among young adult bar patrons.
AB  - OBJECTIVE: To explore the prevalence and sociodemographic makeup of smokers who
      do not self-identify as smokers (ie, phantom smokers) compared with self
      identifying smokers in a sample of bar-going young adults aged 18-30 years to
      more accurately assess young adult prevalence of smoking and inform cessation
      message targeting. METHODS: Cross-sectional surveys of smokers (n=3089) were
      conducted in randomly selected bars/nightclubs in seven US cities. Logistic
      regression models assessed associations between phantom smoking (past 30-day
      smoking and denial of being a smoker), tobacco and alcohol use behaviours (eg,
      social smoking, nicotine dependence, smoking while drinking, past 30-day alcohol
      use) and demographics. RESULTS: Compared with smokers, phantom smokers were more
      likely to be college graduates (OR=1.43, 95% CI 1.03 to 1.98) and to identify
      themselves as social smokers (OR=1.60, 95% CI 1.27 to 2.12). Phantom smokers had
      lower odds of smoking while drinking (OR=0.28, 95% CI 0.25 to 0.32), being
      nicotine dependent (OR=0.36, 95% CI 0.22 to 0.76) and having quit for at least 1
      day in the last year (OR=0.46, 95% CI 0.36 to 0.69) compared with smokers.
      CONCLUSIONS: This research extends phantom smoking literature on college students
      to provide a broader picture of phantom smoking among young adults in high-risk
      contexts and of varying levels of educational attainment. Phantom smokers may be
      particularly sensitive to social pressures against smoking, suggesting the
      importance of identifying smoking as a behaviour (rather than identity) in
      cessation messaging to ensure that phantom smokers are reached.

PMID- 27048206
TI  - Concordance Between Aspiration Detected on Upper Gastrointestinal Series and
      Videofluoroscopic Swallow Study in Bottle-Fed Children.
AB  - The increasing incidence of pediatric dysphagia has raised questions about how to
      identify children at risk for aspiration. Multiple investigative imaging
      modalities are considered in diagnostic algorithms, since dysphagia may involve
      any or all phases of swallowing. Although upper gastrointestinal (UGI) series and
      videofluoroscopic swallow study (VFSS) are common procedures, the utility of UGI
      for detection of aspiration and the impact of oropharyngeal imaging during UGI on
      radiation exposure have not been well described. We hypothesized that diagnosis
      of aspiration on UGI would be predictive of aspiration on VFSS and screening
      swallows during UGI would increase radiation exposure. A retrospective review was
      completed of bottle-fed children undergoing UGI series within 1 month
      before/after standardized VFSS. UGI was imaged at 3 frames per second (fps)
      pulsed and VFSS at 30 fps continuous fluoroscopy. Cumulative radiation dose (CD)
      and dose area product (DAP) were recorded. VFSS and UGI were performed in 49
      patients; however, only 21 (43 %) had documentation of swallow function on an UGI
      series. All children with aspiration on UGI demonstrated thin liquid aspiration
      on VFSS; however, 53 % without aspiration on UGI aspirated on VFSS. CD for UGI
      with versus without swallowing documentation was significantly higher (median =
      0.33 vs. 0.21 mGy, p = 0.02) but within variability ranges reported for
      fluoroscopy equipment. DAP was not significantly higher for UGI with
      documentation of swallowing compared to without documentation of swallowing
      (median = 4.11 vs. 3.02 MUGy cm(2), p = 0.09). UGI findings are specific but not
      sensitive markers for aspiration on VFSS. Imaging of swallowing on UGI may have
      an appreciable increase on radiation exposure.

PMID- 27048207
TI  - Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of
      Poorly Soluble Drugs.
AB  - Low dissolution of drugs in the intestinal fluid can limit their effectiveness in
      oral therapies. Here, a novel porous silica-supported solid lipid system was
      developed to optimize the oral delivery of drugs with limited aqueous solubility.
      Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica
      supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid
      (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica
      A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles
      demonstrated significantly higher rate and extent of lipolysis in comparison with
      the pure solid lipid, depending on the lipid loading levels and the morphology.
      The highest lipid digestion was observed when silica-S was loaded with 34% (w/w)
      solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the
      encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S
      formulation. Drug dissolution under non-digesting intestinal conditions revealed
      a three- to sixfold increase in dissolution efficiencies when compared to the
      unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided
      superior drug solubilization under simulated intestinal digesting condition in
      comparison with the drug-lipid suspension and drug-loaded silica. Therefore,
      solid lipid and nanoporous silica provides a synergistic effect on optimizing the
      solubilization of poorly water-soluble compound and the solid lipid-based porous
      carrier system provides a promising delivery approach to overcome the oral
      delivery challenges of poorly water-soluble drugs.

PMID- 27048208
TI  - Cognitive functioning in meningioma patients: a systematic review.
AB  - This systematic review evaluates relevant findings and methodologic aspects of
      studies on cognitive functioning in meningioma patients prior to and/or following
      surgery with or without adjuvant radiotherapy. PubMed and Web of Science
      electronic databases were searched until December 2015. From 1012 initially
      identified articles, 11 met the inclusion criteria for this review. Multiple
      methodological limitations were identified which include the lack of pre
      treatment assessments, variations in the number and types of neuropsychological
      tests used, the normative data used to identify patients with cognitive deficits,
      and the variety of definitions for cognitive impairment. Study results suggest
      that most of meningioma patients are faced with cognitive deficits in several
      cognitive domains prior to surgery. Following surgery, most of these patients
      seem to improve in cognitive functioning. However, they still have impairments in
      a wide range of cognitive functions compared to healthy controls. Suggestions are
      given for future research. Adequate diagnosis and treatment of cognitive deficits
      may ultimately lead to improved outcome and quality of life in meningioma
      patients.

PMID- 27048209
TI  - Nine in 10 general practices struggle to find locum cover.

PMID- 27048210
TI  - Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of
      Ethanol, Diazepam, and Lithium.
AB  - INTRODUCTION: Because the multimodal antidepressant vortioxetine is likely to be
      coadministered with other central nervous system (CNS)-active drugs, potential
      drug-drug interactions warrant examination. OBJECTIVE: These studies evaluated
      whether there are pharmacokinetic and/or pharmacodynamic interactions between
      vortioxetine and ethanol, diazepam, or lithium. METHODS: This series of phase I
      studies included healthy men and women (only men in the lithium study) aged 18-45
      years. The ethanol study was a randomized, double-blind, two-parallel group, four
      period crossover study in which subjects received a single dose of vortioxetine
      (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a
      randomized, double-blind, placebo-controlled, two-sequence, two-period crossover
      study in which subjects received a single dose of diazepam following multiple
      doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the
      effect of coadministration on standardized psychomotor parameters and on selected
      pharmacokinetic parameters of each drug. The lithium study was a single-blind,
      single-sequence study evaluating the effect of multiple doses of vortioxetine 10
      mg/day on the steady-state pharmacokinetics of lithium. RESULTS: Concomitant
      administration of vortioxetine and single doses of either ethanol or diazepam had
      no significant effect on the psychomotor performance of subjects compared with
      administration of ethanol or diazepam alone. Vortioxetine had no significant
      effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had
      no significant effect on the pharmacokinetics of vortioxetine. CONCLUSIONS:
      Concomitant administration of these agents with vortioxetine was generally well
      tolerated, with no clinically relevant drug-drug pharmacokinetic or
      pharmacodynamic interactions identified.

PMID- 27048212
TI  - How I vaccinate blood and marrow transplant recipients.
AB  - Vaccination guidelines for recipients of blood and marrow transplantation (BMT)
      have been published by 3 major societies: American Blood and Marrow
      Transplantation, European Group of Blood and Marrow Transplantation, and
      Infectious Disease Society of America. Despite these extensive review articles,
      clinicians caring for BMT recipients continue to field frequently asked questions
      (FAQs) regarding the "who, when, and how" of feasible and effective
      posttransplant vaccination, frequently in the absence of adequate data. This may
      reflect discomfort with a "one size fits all" policy that makes no adjustments
      for different posttransplant clinical scenarios. Existing guidelines also lack
      practical dose clarifications when administering vaccines to patients who differ
      by age, underlying diagnosis, or amount of immunosuppressive therapy. Frequently,
      little or conflicting guidance is given regarding age-related schedules for
      certain vaccines (eg, meningococcal; tetanus toxoid, reduced diphtheria toxoid,
      and reduced acellular pertussis; and human papillomavirus vaccines) in addition
      to time posttransplant or other factors. FAQs and their answers form the body of
      this article and are shared with readers as a concise practical review, with the
      intent to facilitate good clinical practice.

PMID- 27048211
TI  - B-cell-specific conditional expression of Myd88p.L252P leads to the development
      of diffuse large B-cell lymphoma in mice.
AB  - The adaptor protein MYD88 is critical for relaying activation of Toll-like
      receptor signaling to NF-kappaB activation. MYD88 mutations, particularly the
      p.L265P mutation, have been described in numerous distinct B-cell malignancies,
      including diffuse large B-cell lymphoma (DLBCL). Twenty-nine percent of activated
      B-cell-type DLBCL (ABC-DLBCL), which is characterized by constitutive activation
      of the NF-kappaB pathway, carry the p.L265P mutation. In addition, ABC-DLBCL
      frequently displays focal copy number gains affecting BCL2 Here, we generated a
      novel mouse model in which Cre-mediated recombination, specifically in B cells,
      leads to the conditional expression of Myd88(p.L252P) (the orthologous position
      of the human MYD88(p.L265P) mutation) from the endogenous locus. These mice
      develop a lymphoproliferative disease and occasional transformation into clonal
      lymphomas. The clonal disease displays the morphologic and immunophenotypical
      characteristics of ABC-DLBCL. Lymphomagenesis can be accelerated by crossing in a
      further novel allele, which mediates conditional overexpression of BCL2 Cross
      validation experiments in human DLBCL samples revealed that both MYD88 and CD79B
      mutations are substantially enriched in ABC-DLBCL compared with germinal center B
      cell DLBCL. Furthermore, analyses of human DLBCL genome sequencing data confirmed
      that BCL2 amplifications frequently co-occurred with MYD88 mutations, further
      validating our approach. Finally, in silico experiments revealed that MYD88
      mutant ABC-DLBCL cells in particular display an actionable addiction to BCL2.
      Altogether, we generated a novel autochthonous mouse model of ABC-DLBCL that
      could be used as a preclinical platform for the development and validation of
      novel therapeutic approaches for the treatment of ABC-DLBCL.

PMID- 27048213
TI  - Population data of 23 STR loci (PowerPlex(r) Fusion System) in Mexican Mestizos
      from the West Region.
AB  - We analyzed 238 unrelated Mestizo (admixed) individuals from the West region of
      Mexico with the PowerPlex(r) Fusion System (Promega Corp.). Allele frequencies
      and forensic parameters were estimated for the 23 STRs included in this kit.
      Hardy-Weinberg equilibrium by locus and non-association between pair of loci were
      demonstrated by exact tests in this population. The combined PE and PD offered by
      this HID kit were >=0.9999999986, representing a substantial improvement with
      respect to those previously offered by 15 STR systems. Interpopulation comparison
      by AMOVA tests demonstrated low but significant differences among Mexican
      Mestizos from West, Center, and Northeast regions (Fst = 0.01558; p = 0.0000),
      similar to the observed among three main ethnic groups from USA (Fst = 0.02048; p
      = 0.0000). This finding is consistent with the contrary clines of European and
      Amerindian ancestries described throughout the Mexican territory for Mestizos,
      the largest population (~90 %) in this country.

PMID- 27048214
TI  - Evaluation of post-mortem lateral cerebral ventricle changes using sequential
      scans during post-mortem computed tomography.
AB  - In the present study, we evaluated post-mortem lateral cerebral ventricle (LCV)
      changes using computed tomography (CT). Subsequent periodical CT scans termed
      "sequential scans" were obtained for three cadavers. The first scan was performed
      immediately after the body was transferred from the emergency room to the
      institute of legal medicine. Sequential scans were obtained and evaluated for 24
      h at maximum. The time of death had been determined in the emergency room. The
      sequential scans enabled us to observe periodical post-mortem changes in CT
      images. The series of continuous LCV images obtained up to 24 h (two cases)/16 h
      (1 case) after death was evaluated. The average Hounsfield units (HU) within the
      LCVs progressively increased, and LCV volume progressively decreased over time.
      The HU in the cerebrospinal fluid (CSF) increased at an individual rate
      proportional to the post-mortem interval (PMI). Thus, an early longitudinal
      radiodensity change in the CSF could be potential indicator of post-mortem
      interval (PMI). Sequential imaging scans reveal post-mortem changes in the CSF
      space which may reflect post-mortem brain alterations. Further studies are needed
      to evaluate the proposed CSF change markers in correlation with other validated
      PMI indicators. 

PMID- 27048215
TI  - How to apply clinical cases and medical literature in the framework of a modified
      "failure mode and effects analysis" as a clinical reasoning tool--an illustration
      using the human biliary system.
AB  - BACKGROUND: Clinicians use various clinical reasoning tools such as Ishikawa
      diagram to enhance their clinical experience and reasoning skills. Failure mode
      and effects analysis, which is an engineering methodology in origin, can be
      modified and applied to provide inputs into an Ishikawa diagram. METHOD: The
      human biliary system is used to illustrate a modified failure mode and effects
      analysis. The anatomical and physiological processes of the biliary system are
      reviewed. Failure is defined as an abnormality caused by infective, inflammatory,
      obstructive, malignancy, autoimmune and other pathological processes. The
      potential failures, their effect(s), main clinical features, and investigation
      that can help a clinician to diagnose at each anatomical part and physiological
      process are reviewed and documented in a modified failure mode and effects
      analysis table. Relevant medical and surgical cases are retrieved from the
      medical literature and weaved into the table. RESULTS: A total of 80 clinical
      cases which are relevant to the modified failure mode and effects analysis for
      the human biliary system have been reviewed and weaved into a designated table.
      The table is the backbone and framework for further expansion. Reviewing and
      updating the table is an iterative and continual process. The relevant clinical
      features in the modified failure mode and effects analysis are then extracted and
      included in the relevant Ishikawa diagram. CONCLUSIONS: This article illustrates
      an application of engineering methodology in medicine, and it sows the seeds of
      potential cross-pollination between engineering and medicine. Establishing a
      modified failure mode and effects analysis can be a teamwork project or self
      directed learning process, or a mix of both. Modified failure mode and effects
      analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn
      can be used to enhance clinical experiences and clinical reasoning skills for
      clinicians, medical educators, and students.

PMID- 27048216
TI  - Hypothesis of Lithocoding: Origin of the Genetic Code as a "Double Jigsaw Puzzle"
      of Nucleobase-Containing Molecules and Amino Acids Assembled by Sequential
      Filling of Apatite Mineral Cellules.
AB  - The hypothesis of direct coding, assuming the direct contact of pairs of coding
      molecules with amino acid side chains in hollow unit cells (cellules) of a
      regular crystal-structure mineral is proposed. The coding nucleobase-containing
      molecules in each cellule (named "lithocodon") partially shield each other; the
      remaining free space determines the stereochemical character of the filling side
      chain. Apatite-group minerals are considered as the most preferable for this type
      of coding (named "lithocoding"). A scheme of the cellule with certain
      stereometric parameters, providing for the isomeric selection of contacting
      molecules is proposed. We modelled the filling of cellules with molecules
      involved in direct coding, with the possibility of coding by their single
      combination for a group of stereochemically similar amino acids. The regular
      ordered arrangement of cellules enables the polymerization of amino acids and
      nucleobase-containing molecules in the same direction (named "lithotranslation")
      preventing the shift of coding. A table of the presumed "LithoCode" (possible and
      optimal lithocodon assignments for abiogenically synthesized alpha-amino acids
      involved in lithocoding and lithotranslation) is proposed. The magmatic nature of
      the mineral, abiogenic synthesis of organic molecules and polymerization events
      are considered within the framework of the proposed "volcanic scenario".

PMID- 27048217
TI  - Association between socioeconomic status and metabolic control and diabetes
      complications: a cross-sectional nationwide study in Chinese adults with type 2
      diabetes mellitus.
AB  - BACKGROUND: Low socioeconomic status (SES) is associated with adverse
      cardiovascular risk factor patterns and poor outcomes in patients with diabetes.
      The aim of this study was to determine whether SES is associated with the control
      of blood glucose, blood pressure, blood cholesterol (3Bs), and diabetic
      complications in Chinese adults with type 2 diabetes. METHODS: Data regarding
      patients' demographics, social economics, diabetes complications, and
      cardiovascular risk profiles were analyzed for 25,454 patients. The outcomes of
      interest were the proportions of patients with HbA1c <7.0 %, blood pressure
      <140/80 mmHg, total serum cholesterol <4.5 mmol/L, and diabetes complications.
      Multivariable logistic regression was used for analysis. RESULTS: Of the 25,454
      patients, the least educated patients (1695, 6.7 %) had the highest chances of
      developing cardiovascular diseases (p = 0.048), cerebrovascular diseases (p <
      0.001), and retinopathy (p < 0.001). The patients with lowest household income
      (10,039, 40.8 %) had the highest prevalence of retinopathy (p < 0.001) and
      neuropathy (p < 0.001). The most educated patients were more likely than the
      least educated patients to achieve HbA1c <7.0 % [adjusted odds ratio (OR) 1.38;
      95 % confidence interval (95 % CI) 1.22-1.56] and 3B goals (adjusted OR 1.30; 95
      % CI 1.11-1.53). The patients with highest household income were more likely to
      achieve BP < 140/80 mmHg (adjusted OR 1.16; 95 % CI 1.07-1.27), but less likely
      to reach HbA1c < 7.0 % (adjusted OR 0.90; 95 % CI 0.83-0.98) than those lowest
      income patients. CONCLUSIONS: Low SES was associated with poor metabolic control
      and more diabetes complications in adult patients in China. Individual diabetes
      management based on the SES of patients is encouraged.

PMID- 27048219
TI  - Management of chest drainage tubes after lung surgery.
AB  - Since chest tubes have been routinely used to drain the pleural space,
      particularly after lung surgery, the management of chest tubes is considered to
      be essential for the thoracic surgeon. The pleural drainage system requires
      effective drainage, suction, and water-sealing. Another key point of chest tube
      management is that a water seal is considered to be superior to suction for most
      air leaks. Nowadays, the most common pleural drainage device attached to the
      chest tube is the three-bottle system. An electronic chest drainage system has
      been developed that is effective in standardizing the postoperative management of
      chest tubes. More liberal use of digital drainage devices in the postoperative
      management of the pleural space is warranted. The removal of chest tubes is a
      common procedure occurring almost daily in hospitals throughout the world.
      Extraction of the tube is usually done at the end of full inspiration or at the
      end of full expiration. The tube removal technique is not as important as how it
      is done and the preparation for the procedure. The management of chest tubes must
      be based on careful observation, the patient's characteristics, and the operative
      procedures that had been performed. 

PMID- 27048218
TI  - Lipopolysaccharide Preconditioning Induces an Anti-inflammatory Phenotype in BV2
      Microglia.
AB  - Increasing evidence indicates that endotoxin tolerance is an essential immune
      homeostatic response to repeated exposure to lipopolysaccharide (LPS) that
      induces a state of altered responsiveness in macrophage, resulting in repression
      of pro-inflammatory gene expression and increased expression of factors that
      mediate the resolution of inflammation. In this study, quantitative real-time
      polymerase chain reaction and Western blot for M1 and M2 markers were performed
      to characterize phenotypic changes of BV2 microglia. We found that the cytokine
      and chemokine expression during endotoxin tolerance were mostly similar to those
      found during M2 polarization. We further examined the expression of M1 and M2
      markers in CD11b+ BV2 by double immunofluorescent staining. The expression of M2
      markers (CD206) increased, whereas the expression of M1 (CD54) markers reduced
      during endotoxin tolerance. Moreover, expression of different transcription
      factor, known for their function in the regulation of pro- and anti-inflammatory
      reaction, was also different. Our data demonstrate that repeat LPS treatment
      activates a differentiation program that leads to microglial polarization toward
      M2-like phenotype.

PMID- 27048220
TI  - Cochrane in CORR ((r)): Ultrasound and Shockwave Therapy for Acute Fractures in
      Adults (Review).

PMID- 27048221
TI  - CORR Insights(r): Survival in Mesenchymal Chondrosarcoma Varies Based on Age and
      Tumor Location: A Survival Analysis of the SEER Database.

PMID- 27048222
TI  - A Simple and Selective Fluorescent Sensor for Zn(2+) and H(+) Ions in Aqueous
      Solution with OR Logic Gate Function.
AB  - The synthesis and properties of a new compound, viz., (N,N'-[1,10-phenanthroline
      4,7-diyldi((E)methylylidene)]bis(1,10-phenanthrolin-5-amine) (1), is described.
      Compound 1 can be used as a selective fluorescent Zn(2+) sensor in buffered
      solution. Furthermore, 1 induces turn on fluorogenic response to H(+) ions.
      Finally, it is shown that an OR logic gate can be constructed with 1 by using
      Zn(2+) and H(+) as two-inputs. Graphical Abstract In this paper, the design,
      synthesis and physicochemical properties of a new compound 1 based on 1,10
      phenanthroline scaffold, is reported. It is noted that 1 can be used as a
      selective fluorescent Zn(2+) sensor in 0.01 M HEPES buffer containing DMF (2 %
      v/v, pH = 7.4) at room temperature. Furthermore, the spectrophotometric results
      suggest that compound 1 can be used as a pH reporter in highly acidic conditions
      (pH < 5). Finally, it was also shown that an OR logic gate can be constructed
      with 1 by using Zn(2+) and H(+) as two-inputs. 

PMID- 27048223
TI  - A Novel Chromone Schiff-Base Fluorescent Chemosensor for Cd(II) Based on C=N
      Isomerization.
AB  - A new chromone Schiff-base fluorescent probe 7'-methoxychromone-3'-methylidene
      1,2,4-triazole-3-imine (L) was designed and synthesized for selective recognition
      Cd(2+). With the fluorescence titration and the ESI-MS data, we reach the
      conclusion that the binding mode of the ligand-metal (L-Cd (2+) ) complex is 1:1.
      The sensor showed a strong fluorescence enhancement in ethanol system of Cd(2+)
      (excitation 409 nm and emission 462 nm) and the sensing mechanism based on the
      fact that C=N isomerization can be used to explain this phenomenon. 

PMID- 27048224
TI  - Novel PAMAM Dendron as a Bichromophoric Probe Based on Rhodamine 6G and 1,8
      Naphthalimide.
AB  - A novel PAMAM dendron designed as a wavelength-shifting bichromophore with 1,8
      naphthalimide energy "donor" capable of absorbing light and efficiently
      transferring the energy to a focal Rhodamine 6G "acceptor" was synthesized and
      investigated. Moreover, the system was configured on the "fluorophore-spacer
      receptor" format. Thus, the distinguishing features of FRET systems were
      successfully combined with the properties of photoinduced electron transfer and
      classical ring-opening sensor systems. The synthesized compound shows excellent
      signaling properties towards protons, Hg(2+) and Fe(3+) ions, therefore, the
      system is able to act as an one-output combinatorial logic circuit with four
      chemical inputs. 

PMID- 27048225
TI  - Microwave Assisted Synthesis, Spectrofluorometric Characterization of Azomethine
      as Intermediate for Transition Metal Complexes with Biological Application.
AB  - Azomethine (1, 5 - Dimethyl - 2 - phenyl -[(3, 4, 5 -trimethoxybenzylidene)
      amino] -1, 2 - dihydropyrazol - 3 - one) (DTAD) was synthesized by the reaction
      of 4-aminophenazone with 3,4,5 trimrthoxybenzaldehyd by microwave irradiation.
      Physicochemical studies such as electronic absorption, molar absorptivity,
      oscillator strength, dipole moment, florescent quantum yield were investigated in
      order to explore the analytical potential of azomethine dye. Azomethine go
      through the solubilization in different micelles and may be used as a probe or
      quencher to determine the critical micelle concentration (CMC) of SDS and CTAB.
      It's coordinate to metal salt through the pyrazol-3-one oxygen and the azomethine
      nitrogen. The structure of ligand and its meal complexes was elucidated by IR,
      (1)H, (13)C-NMR, EI-MS spectroscopic methods and elemental analysis. The
      antibacterial activity of these compounds were first tested in vitro by the disc
      diffusion assay against two Gram-positive and two Gram-negative bacteria, and
      then the minimum inhibitory concentration was using chloramphenicol as reference
      drug. The results showed that compound 1.1 is better inhibitor of both types of
      tested bacteria as compared to chloramphenicol. 

PMID- 27048226
TI  - Spectroscopic Study of CpG Alternating DNA-Methylene Blue Interaction for
      Methylation Detection.
AB  - Recognition of methylated DNA sites would be useful strategy due to the important
      roles of methylation in disease occurrence and developmental processes. The
      interaction of CpG rich methylated and unmethylated DNA hybrid with methylene
      blue (MB) as an optical probe has been investigated by absorption, emission,
      circular dichorism and fluorescence anisotropy analysis. Titration of MB with
      both sequences caused a hypsochromism and decreased the absorption of MB that
      indicating an intercalative mode of interaction. The experimental results
      revealed that MB as the optical indicator could distinguish between the
      methylated and unmethylated DNA sequences. Under optimum conditions, upon the
      addition of methylated dsDNA, the fluorescence intensity increased in linear
      range from 1.0 * 10(-9) to 1.0 * 10(-6) M with detection limit of 7.2 * 10(-10) M
      and on the other hand, the intensity of MB showed no change with addition of
      unmethylated dsDNA. 

PMID- 27048227
TI  - The lack of Lazarus effect with proteasome inhibition.
AB  - There have been marked improvements in the short- and long-term outcomes for
      children after renal transplantation over the past two decades with superior
      quality and quantity of life. It is encouraging to see increased patient and
      renal allograft survival rates with initially lower acute renal allograft
      rejection rates due to improved matching and immunosuppressive regimens.
      Unfortunately, longer-term renal allograft survival remains unchanged with
      chronic allograft injury from both immune and non-immune causes, resulting in
      chronic allograft dysfunction, morbidity from chronic kidney disease, and
      eventual renal allograft loss. Acute and chronic antibody-mediated rejection
      remains a clinical dilemma with a growing evidence base of its treatment,
      including proteasome inhibition using intravenous bortezomib. The future goal is
      to reduce chronic allograft dysfunction and make renal transplants last longer
      for pediatric renal transplant recipients who may require retransplantation
      during their childhood and adult lives, which can become successively more
      difficult due to sensitization.

PMID- 27048229
TI  - Erratum to: Health-related quality of life and mental health in parents of
      children with hemolytic uremic syndrome.

PMID- 27048228
TI  - Bortezomib may stabilize pediatric renal transplant recipients with antibody
      mediated rejection.
AB  - BACKGROUND: Current therapeutic strategies to effectively treat antibody-mediated
      rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a
      therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric
      kidney transplant patients. METHODS: We examined seven patients with treatment
      refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti
      CD25 monoclonal antibody for induction therapy with maintenance corticosteroids,
      calcineurin inhibitor, and anti-metabolite. Estimated glomerular filtration rate
      (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013
      Banff criteria, and human leukocyte antigen (HLA) donor-specific antibodies (DSA)
      performed using the Luminex single antigen bead assay were monitored pre- and
      post- bortezomib therapy. RESULTS: Seven patients (86 % male, 86 % with >=6/8 HLA
      mismatch, and 14 % with pre-formed DSA) age 5 to 19 (median 15) years developed
      refractory C4d + AMR between 1 and 145 (median 65) months post-transplantation.
      All patients tolerated bortezomib. One patient had allograft loss. Of the six
      patients with surviving grafts (86 %), mean pre-bortezomib eGFR was 42
      ml/min/1.73 m(2) and the mean 1 year post-bortezomib eGFR was 53 ml/min/1.73
      m(2). Five of seven (71 %) had improvement of histological findings of AMR, C4d
      staining, and/or acute cellular rejection. Reduction in HLA DSAs was more
      effective for class I than class II. CONCLUSIONS: Bortezomib appears safe and may
      correlate with stabilization of eGFR in pediatric kidney transplant patients with
      refractory C4d + AMR.

PMID- 27048230
TI  - Kidney retransplantation in children following rejection and recurrent disease.
AB  - Retransplantation accounts for approximately 15 % of the annual transplants
      performed in the USA, and in the recent International Collaborative Transplant
      Study report on pediatric patients 15.2 % of the 9209 patients included in the
      report were retransplant recipients. Although the significant advances in
      clinical management and newer immunosuppressive agents have had a significant
      impact on improving short-term allograft function, it is apparent that long-term
      allograft function remains suboptimal. Therefore, it is likely that the majority
      of pediatric renal allograft recipients will require one or more retransplants
      during their lifetime. Unfortunately, a second or subsequent graft in pediatric
      recipients has inferior long-term graft survival rates compared to initial
      grafts, with decreasing rates with each subsequent graft. Multiple issues
      influence the outcome of retransplantation, with the most significant being the
      cause of the prior transplant failure. Non-adherence-associated graft loss poses
      unresolved ethical issues that may impact access to retransplantation. Graft
      nephrectomy prior to retransplantation may benefit selected patients, but the
      impact of an in situ failed graft on the development of panel-reactive antibodies
      remains to be definitively determined. It is important that these and other
      factors discussed in this review be taken into consideration during the
      counseling of families on the optimal approach for their child who requires a
      retransplant.

PMID- 27048231
TI  - Assessing acute kidney injury after pediatric heart transplant.

PMID- 27048232
TI  - Estrogens maintain skeletal muscle and satellite cell functions.
AB  - Estrogens have crucial roles in an extensive range of physiological functions
      regulating cellular proliferation and differentiation, development, homeostasis,
      and metabolism. Therefore, prolonged estrogen insufficiency influences various
      types of tissues expressing estrogen receptors (ERs). Although ERs are expressed
      in skeletal muscle and its stem cells, called satellite cells, how prolonged
      estrogen insufficiency affects their function remains unclear. In this study, we
      investigated the effect of estrogen reduction on muscle in young ovariectomized
      (OVX) female mice. We found that reduced estrogens resulted in muscle atrophy in
      a time-dependent manner. Muscle force generation was reduced in OVX mice.
      Interestingly, prolonged estrogen insufficiency shifted fiber types toward faster
      myosin heavy chain isoforms. The number of satellite cells per isolated myofiber
      was unchanged, while satellite cell expansion, differentiation, and self-renewal
      were all markedly impaired in OVX mice. Indeed, muscle regeneration was
      significantly compromised in OVX mice. Taken together, our results demonstrate
      that estrogens are essential for comprehensively maintaining muscle function with
      its insufficiency affecting muscle strength and regeneration in young female
      mice.

PMID- 27048235
TI  - Engagement of Gay Men and Other Men Who Have Sex with Men (MSM) in the Response
      to HIV: A Critical Step in Achieving an AIDS-Free Generation.
AB  - Men who have sex with men (MSM) continue to be at elevated risk for HIV
      acquisition and transmission secondary to biological and behavioral
      characteristics, social and sexual network characteristics, community
      environmental factors, and structural factors. HIV incidence rates remain high
      among MSM in both low- and high-income settings, and in both concentrated and
      more generalized HIV epidemic settings. While data quality tends to be poorer,
      the best estimates collectively suggest that MSM have up to 20 times the odds of
      living with HIV as compared to other reproductive aged adults across low- and
      middle-income countries. Recent prevention strategies to lower biological HIV
      transmission and acquisition risks, including the early use of antiretrovirals to
      decrease infectiousness for those living with HIV, and pre-exposure prophylaxis
      for those at significant risk of HIV acquisition, have demonstrated the potential
      to change the trajectory of the HIV epidemics among MSM. However, the coverage
      and effectiveness of these approaches is limited by structural factors including
      the punitive legal frameworks and institutional discrimination that contribute to
      limited uptake, challenges to adherence, and suboptimal health-seeking behaviors
      among MSM. More intensive efforts will be required to reach MSM who do not
      currently have access to relevant and effective prevention and treatment services
      or elect not to access these services given enacted and/or perceived stigma.
      Respect for human rights, including efforts to aggressively confront and combat
      the forms of stigma that are preventing us from achieving an AIDS-Free
      generation, are needed for all people including gay men and other MSM.

PMID- 27048234
TI  - GLP2: an underestimated signal for improving glycaemic control and insulin
      sensitivity.
AB  - Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide produced by
      intestinal enteroendocrine L-cells and by a discrete population of neurons in the
      brainstem, which projects mainly to the hypothalamus. The main biological actions
      of GLP2 are related to the regulation of energy absorption and maintenance of
      mucosal morphology, function and integrity of the intestine; however, recent
      experimental data suggest that GLP2 exerts beneficial effects on glucose
      metabolism, especially in conditions related to increased uptake of energy, such
      as obesity, at least in the animal model. Indeed, mice lacking GLP2 receptor
      selectively in hypothalamic neurons that express proopiomelanocortin show
      impaired postprandial glucose tolerance and hepatic insulin resistance (by
      increased gluconeogenesis). Moreover, GLP2 acts as a beneficial factor for
      glucose metabolism in mice with high-fat diet-induced obesity. Thus, the aim of
      this review is to update and summarize current knowledge about the role of GLP2
      in the control of glucose homeostasis and to discuss how this molecule could
      exert protective effects against the onset of related obesity type 2 diabetes.

PMID- 27048233
TI  - Glucocorticoids and 11beta-HSD1 are major regulators of intramyocellular protein
      metabolism.
AB  - The adverse metabolic effects of prescribed and endogenous glucocorticoid excess,
      'Cushing's syndrome', create a significant health burden. While skeletal muscle
      atrophy and resultant myopathy is a clinical feature, the molecular mechanisms
      underpinning these changes are not fully defined. We have characterized the
      impact of glucocorticoids upon key metabolic pathways and processes regulating
      muscle size and mass including: protein synthesis, protein degradation, and
      myoblast proliferation in both murine C2C12 and human primary myotube cultures.
      Furthermore, we have investigated the role of pre-receptor modulation of
      glucocorticoid availability by 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) in these processes. Corticosterone (CORT) decreased myotube area, decreased
      protein synthesis, and increased protein degradation in murine myotubes. This was
      supported by decreased mRNA expression of insulin-like growth factor (IGF1),
      decreased activating phosphorylation of mammalian target of rapamycin (mTOR),
      decreased phosphorylation of 4E binding protein 1 (4E-BP1), and increased mRNA
      expression of key atrophy markers including: atrogin-1, forkhead box O3a
      (FOXO3a), myostatin (MSTN), and muscle-ring finger protein-1 (MuRF1). These
      findings were endorsed in human primary myotubes, where cortisol also decreased
      protein synthesis and increased protein degradation. The effects of 11
      dehydrocorticosterone (11DHC) (in murine myotubes) and cortisone (in human
      myotubes) on protein metabolism were indistinguishable from that of CORT/cortisol
      treatments. Selective 11beta-HSD1 inhibition blocked the decrease in protein
      synthesis, increase in protein degradation, and reduction in myotube area induced
      by 11DHC/cortisone. Furthermore, CORT/cortisol, but not 11DHC/cortisone,
      decreased murine and human myoblast proliferative capacity. Glucocorticoids are
      potent regulators of skeletal muscle protein homeostasis and myoblast
      proliferation. Our data underscores the potential use of selective 11beta-HSD1
      inhibitors to ameliorate muscle-wasting effects associated with glucocorticoid
      excess.

PMID- 27048236
TI  - Acceptability of Three Novel HIV Prevention Methods Among Young Male and
      Transgender Female Sex Workers in Puerto Rico.
AB  - Sex workers need HIV-prevention methods they can control and incorporate easily
      in their work. We studied the acceptability of three methods: HIV self-test use
      with clients, oral pre-exposure prophylaxis (PrEP), and rectal microbicide gel.
      Four male and eight transgender female (TGF) sex workers in Puerto Rico completed
      a baseline survey with a quantitative measure of likelihood of use. From them,
      one male and four TGF also completed a 12-week study of rectal microbicide
      placebo gel use prior to receptive anal intercourse with male clients and
      evaluated via qualitative in-depth interviews and follow-up quantitative
      assessments how each method could be incorporated into their work. Most were
      interested in a rectal microbicide gel and able to use it covertly with clients.
      Challenges to using the HIV self-test with clients included the potential for
      both breach of confidentiality and confronting violent situations. Participants
      also expressed interest in oral PrEP, but raised concerns about side effects.

PMID- 27048237
TI  - Relationship-Based Predictors of Sexual Risk for HIV Among MSM Couples: A
      Systematic Review of the Literature.
AB  - Behavioral and epidemiological studies report high risk for HIV among MSM
      couples. Over the last decade, studies have examined relationship dynamics
      associated with sexual risk for HIV. It is important to examine the impact this
      research has had on HIV prevention and what is still needed. We conducted a
      review of the literature focusing on relationship dynamics associated with sexual
      risk for HIV among MSM couples. Procedures used for this review were guided by
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      established to provide a framework for collecting, reviewing and reporting
      studies systematically (Mohler et al. in Ann Intern Med 151(4):264-269, 2009). We
      found that positive relationship dynamics are associated with less risk with
      partners outside the relationship, but were associated with greater odds of
      unprotected anal intercourse with primary partners. We also discuss other factors
      including sexual agreements about outside partners and make recommendations for
      next steps in HIV prevention research among MSM couples.

PMID- 27048238
TI  - A study on the genetic relationships of Avena taxa and the origins of hexaploid
      oat.
AB  - KEY MESSAGE: Using next-generation DNA sequencing, it was possible to clarify the
      genetic relationships of Avena species and deduce the likely pathway from which
      hexaploid oat was formed by sequential polyploidization events. A sequence-based
      diversity study was conducted on a representative sample of accessions from
      species in the genus Avena using genotyping-by-sequencing technology. The results
      show that all Avena taxa can be assigned to one of four major genetic clusters:
      Cluster 1 = all hexaploids including cultivated oat, Cluster 2 = AC genome
      tetraploids, Cluster 3 = C genome diploids, Cluster 4 = A genome diploid and
      tetraploids. No evidence was found for the existence of discrete B or D genomes.
      Through a series of experiments involving the creation of in silico polyploids,
      it was possible to deduce that hexaploid oat likely formed by the fusion of an
      ancestral diploid species from Cluster 3 (A. clauda, A. eriantha) with an
      ancestral diploid species from Cluster 4D (A. longiglumis, A. canariensis, A.
      wiestii) to create the ancestral tetraploid from Cluster 2 (A. magna, A. murphyi,
      A. insularis). Subsequently, that ancestral tetraploid fused again with another
      ancestral diploid from Cluster 4D to create hexaploid oat. Based on the
      geographic distribution of these species, it is hypothesized that both the
      tetraploidization and hexaploidization events may have occurred in the region of
      northwest Africa, followed by radiation of hexaploid oat to its current worldwide
      distribution. The results from this study shed light not only on the origins of
      this important grain crop, but also have implications for germplasm collection
      and utilization in oat breeding.

PMID- 27048239
TI  - Quality of Life Among Food Allergic Patients and Their Caregivers.
AB  - Food allergy is increasing in prevalence worldwide. This review summarizes
      progress made studying relationships between food allergy and quality of life
      (QOL), with an emphasis on recent work in the field. Early work examining QOL
      among food allergy patients established that stress and anxiety associated with
      continuous allergen avoidance and the looming threat of anaphylaxis were
      associated with significantly impaired food allergy quality of life (FAQOL) for
      children with food allergy and their caregivers. Recent clinical studies suggest
      that undergoing oral food challenge to confirm food allergy and oral
      immunotherapy to treat food allergy may each improve FAQOL among both patients
      and their caregivers. Other intervention modalities, such as nurse-facilitated
      counseling and educational workshops, also hold promise, but additional work is
      needed. Future work must strive to recruit more representative, population-based
      samples, including adult patients, in order to improve the generalizability and
      clinical relevance of findings. 

PMID- 27048240
TI  - Gambling, Risk-Taking, and Antisocial Behavior: A Replication Study Supporting
      the Generality of Deviance.
AB  - Research suggests that high frequency gambling is a component of the "generality
      of deviance", which describes the observation that various forms of risky and
      antisocial behavior tend to co-occur among individuals. Furthermore, risky and
      antisocial behaviors have been associated with such personality traits as low
      self-control, and impulsivity, and sensation-seeking. We conducted a replication
      (and extension) of two previous studies examining whether high frequency gambling
      is part of the generality of deviance using a large and diverse community sample
      (n = 328). This study was conducted as a response to calls for more replication
      studies in the behavioral and psychological sciences (recent systematic efforts
      suggest that a significant proportion of psychology studies do not replicate).
      The results of the present study largely replicate those previously found, and in
      many cases, we observed stronger associations among measures of gambling, risk
      taking, and antisocial behavior in this diverse sample. Together, this study
      provides evidence for the generality of deviance inclusive of gambling (and, some
      evidence for the replicability of research relating to gambling and individual
      differences).

PMID- 27048241
TI  - Tailgut Cyst in a Neonate: A Case Report.

PMID- 27048242
TI  - Photobacterium sanguinicancri sp. nov. isolated from marine animals.
AB  - Six strains were isolated from the hemolymph of the spider crab Maja
      brachydactyla, captured in Spain, and one from a diseased blue mussel, Mytilus
      edulis. The 16S rRNA gene sequences showed close similarity to the recently
      described Photobacterium swingsii (98.1 %) and to a lesser degree to
      Photobacterium aquimaris (97.8 %). MLSA analyses showed a monophyletic group
      including P. swingsii that form a new subclade. All genomic analyses (Average
      Nucleotide Identity, Average Amino Acid Identity, and in silico DNA-DNA) clearly
      separate the strains analysed from P. swingsii with values below the thresholds
      to delimit a new species. The phenotypic, genotypic and genomic data presented
      here clearly place these strains as a coherent group within the genus
      Photobacterium, for which we propose the name Photobacterium sanguinicancri sp.
      nov. Strain CAIM 1827(T) (=CECT 7579(T), =DSM 24670(T)) is proposed as the type
      strain of the species. 

PMID- 27048243
TI  - A decade of contributions to understanding and ameliorating attention deficit
      hyperactivity disorder.
AB  - BACKGROUND: It has been 10 years since Terje Sagvolden founded Behavioral and
      Brain Functions. BODY: After setting the context, this paper reviews some of the
      contributions of articles in the journal to the literature on ADHD over that
      decade. Those articles provide a cross section of some of the most important
      ongoing themes in ADHD research. CONCLUSION: Terje's faith in the new journal was
      well founded. It has survived the first threat of new journals, crib death,
      because of the continuing quality and relevance of the articles it carries. It
      has a diversified portfolio of similar research in many other fields of related
      interest.

PMID- 27048244
TI  - When to write a neurology case report.
AB  - Case report publication has seen a resurgence in recent years as awareness of the
      value of case reports in clinical medicine has grown. Not all areas of medical
      research are amenable to large clinical trials. Many topics are better addressed
      by more detailed descriptions of multi-factorial components that contribute to
      outcomes, and these are areas where case reports shine. Determining the
      suitability of a case for publication requires background research and
      discussion. Writing a case or series reinforces many aspects of the medical
      training process, and house staff are encouraged to research, write, and submit
      reports. The medical community benefits in many ways from case reports, from
      improving individual patient care to guiding future research directions. 

PMID- 27048245
TI  - Activation of IGF1R/p110beta/AKT/mTOR confers resistance to alpha-specific PI3K
      inhibition.
AB  - BACKGROUND: The PI3K pathway is hyperactivated in many cancers, including 70 % of
      breast cancers. Pan- and isoform-specific inhibitors of the PI3K pathway are
      currently being evaluated in clinical trials. However, the clinical responses to
      PI3K inhibitors when used as single agents are not as efficient as expected.
      METHODS: In order to anticipate potential molecular mechanisms of resistance to
      the p110alpha isoform-selective inhibitor BYL719, we developed resistant breast
      cancer cell lines, assessed the concomitant changes in cellular signaling
      pathways using unbiased phosphotyrosine proteomics and characterized the
      mechanism of resistance using pharmacological inhibitors. RESULTS: We found an
      increase in IGF1R, IRS1/IRS2 and p85 phosphorylation in the resistant lines. Co
      immunoprecipitation experiments identified an IGF1R/IRS/p85/p110beta complex that
      causes the activation of AKT/mTOR/S6K and stifles the effects of BYL719.
      Pharmacological inhibition of members of this complex reduced mTOR/S6K activation
      and restored sensitivity to BYL719. CONCLUSION: Our study demonstrates that the
      IGF1R/p110beta/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast
      cancers. This provides a rationale for the combined targeting of p110alpha with
      IGF1R or p110beta in patients with breast tumors harboring PIK3CA mutations.

PMID- 27048247
TI  - Breastfeeding Continuation Among Late Preterm Infants: Barriers, Facilitators,
      and Any Association With NICU Admission?
AB  - BACKGROUND AND OBJECTIVES: Late preterm birth (at 34-36 6/7 weeks' gestation) is
      a risk factor for early breastfeeding cessation. The objective of this study was
      to determine barriers to and facilitators of breastfeeding continuation among
      late preterm infants (LPI) and to compare the barriers faced by LPI admitted to
      the well nursery versus the NICU. METHODS: The SAS Complex Survey was used to
      perform multivariable logistic regression analysis by using data from the Centers
      for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System.
      Data from 3 states (Illinois, Maine, and Vermont) for the years 2004 to 2008 were
      used. RESULTS: A total of 2530 mothers of LPI were surveyed. Odds of
      breastfeeding initiation were similar among LPI admitted to the NICU versus the
      well nursery (adjusted odds ratio, 1.24 [95% confidence interval, 0.88-1.73]; P =
      .209). Odds of breastfeeding for >= 10 weeks were no different between LPI
      admitted to the NICU versus those admitted to the well-nursery (adjusted odds
      ratio, 1.02 [95% confidence interval, 0.73-1.43]; P = .904). Factors associated
      with increased odds of breastfeeding for >= 10 weeks among LPI were higher
      maternal education, mother being married, and normal maternal BMI. Regardless of
      NICU admission, the top reasons cited by mothers of LPI for early breastfeeding
      discontinuation were perceived inadequate milk supply and nursing difficulties.
      CONCLUSIONS: Among LPIs, NICU admission was not associated with early
      breastfeeding cessation. Mothers of LPIs with lower odds of sustaining
      breastfeeding for at least 10 weeks were single mothers, those with a high school
      education only, and those who were obese. Breastfeeding support should be
      enhanced for LPIs and should address perceived maternal milk supply concerns and
      nursing difficulties.

PMID- 27048246
TI  - BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict
      Responsiveness to BRAF-MEK Combination Therapy.
AB  - Neuroendocrine tumors comprise a heterogeneous group of malignancies with a broad
      spectrum of clinical behavior. Poorly differentiated tumors follow an aggressive
      course with limited treatment options, and new approaches are needed. Oncogenic
      BRAF V600E (BRAF(V600E)) substitutions are observed primarily in melanoma, colon
      cancer, and non-small cell lung cancer, but have been identified in multiple
      tumor types. Here, we describe the first reported recurrent BRAF(V600E) mutations
      in advanced high-grade colorectal neuroendocrine tumors and identify a BRAF
      alteration frequency of 9% in 108 cases. Among these BRAF alterations, 80% were
      BRAF(V600E) Dramatic response to BRAF-MEK combination therapy occurred in two
      cases of metastatic high-grade rectal neuroendocrine carcinoma refractory to
      standard therapy. Urinary BRAF(V600E) circulating tumor DNA monitoring paralleled
      disease response. Our series represents the largest study of genomic profiling in
      colorectal neuroendocrine tumors and provides strong evidence that BRAF(V600E) is
      an oncogenic driver responsive to BRAF-MEK combination therapy in this molecular
      subset. SIGNIFICANCE: BRAF(V600E) is an established oncogenic driver, but
      significant disparities in response exist among tumor types. Two patients with
      treatment-refractory high-grade colorectal neuroendocrine tumors harboring
      BRAF(V600E) exhibited rapid and durable response to combined BRAF-MEK inhibition,
      providing the first clinical evidence of efficacy in this aggressive tumor type.
      Cancer Discov; 6(6); 594-600. (c)2016 AACR.This article is highlighted in the In
      This Issue feature, p. 561.

PMID- 27048249
TI  - Can we make a better beta cell?

PMID- 27048248
TI  - Changes in beta cell function occur in prediabetes and early disease in the Lepr
      (db) mouse model of diabetes.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is a progressive disease that increases
      morbidity and the risk of premature death. Glucose dysregulation, such as
      elevated fasting blood glucose, is observed prior to diabetes onset. A decline in
      beta cell insulin secretion contributes to the later stages of diabetes, but it
      is not known what, if any, functional beta cell changes occur in prediabetes and
      early disease. METHODS: The Lepr (db) mouse (age 13-18 weeks) was used as a model
      of type 2 diabetes and a two-photon granule fusion assay was used to characterise
      the secretory response of pancreatic beta cells. RESULTS: We identified a
      prediabetic state in db/db mice where the animals responded normally to a glucose
      challenge but have elevated fasting blood glucose. Isolated islets from
      prediabetic animals secreted more and were bigger. Insulin secretion, normalised
      to insulin content, was similar to wild type but basal insulin secretion was
      elevated. There was increased glucose-induced granule fusion with a high
      prevalence of granule-granule fusion. The glucose-induced calcium response was
      not changed but there was altered expression of the exocytic machinery. db/db
      animals at the next stage of disease had overt glucose intolerance. Isolated
      islets from these animals had reduced insulin secretion, reduced glucose-induced
      granule fusion events and decreased calcium responses to glucose.
      CONCLUSIONS/INTERPRETATION: Beta cell function is altered in prediabetes and
      there are further changes in the progression to early disease.

PMID- 27048250
TI  - Hepatic glucose and lipid metabolism.
AB  - The liver has a central role in the regulation of systemic glucose and lipid
      fluxes during feeding and fasting and also relies on these substrates for its own
      energy needs. These parallel requirements are met by coordinated control of
      carbohydrate and lipid fluxes into and out of the Krebs cycle, which is highly
      tuned to nutrient availability and heavily regulated by insulin and glucagon.
      During progression of type 2 diabetes, hepatic carbohydrate and lipid
      biosynthesis fluxes become elevated, thus contributing to hyperglycaemia and
      hypertriacylglycerolaemia. Over this interval there are also significant
      fluctuations in hepatic energy state. To date, it is not known to what extent
      abnormal glucose and lipid fluxes are causally linked to altered energy states.
      Recent evidence that the glucose-lowering effects of metformin appear to be
      mediated by attenuation of hepatic energy generation places an additional
      spotlight on the interdependence of hepatic biosynthetic and oxidative fluxes.
      The transition from fasting to feeding results in a significant re-direction of
      hepatic glucose and lipid fluxes and may also incur a temporary hepatic energy
      deficit. At present, it is not known to what extent these variables are
      additionally modified by type 2 diabetes and/or non-alcoholic fatty liver
      disease. Thus, there is a compelling need to measure fluxes through oxidative,
      gluconeogenic and lipogenic pathways and determine their relationship with
      hepatic energy state in both fasting and fed conditions. New magnetic resonance
      based technologies allow these variables to be non-invasively studied in animal
      models and humans. This review summarises a presentation given at the symposium
      entitled 'The liver in focus' at the 2015 annual meeting of the EASD. It is
      accompanied by two other reviews on topics from this symposium (by Kenneth Cusi,
      DOI: 10.1007/s00125-016-3952-1 , and by Hannele Yki-Jarvinen, DOI: 10.1007/s00125
      016-3944-1 ) and a commentary by the Session Chair, Michael Roden (DOI:
      10.1007/s00125-016-3911-x ).

PMID- 27048251
TI  - Functional dyspepsia: new insights into pathogenesis and therapy.
AB  - One in 10 people suffer from functional dyspepsia (FD), a clinical syndrome
      comprising chronic bothersome early satiety, or postprandial fullness, or
      epigastric pain or burning. Postprandial distress syndrome (PDS, comprising early
      satiety and/or postprandial fullness) and epigastric pain syndrome (EPS) are
      increasingly accepted as valid clinical entities, based on new insights into the
      pathophysiology and the results of clinical trials. Diagnosis is based on the
      clinical history, and exclusion of peptic ulcer and cancer by endoscopy. Evidence
      is accumulating FD and gastroesophageal ref lux disease are part of the same
      disease spectrum in a major subset. The causes of FD remain to be established,
      but accumulating data suggest infections and possibly food may play an important
      role in subsets. FD does not equate with no pathology; duodenal eosinophilia is
      now an accepted association, and Helicobacter pylori infection is considered to
      be causally linked to dyspepsia although only a minority will respond to
      eradication. In those with EPS, acid suppression therapy is a first line therapy;
      consider a H2 blocker even if proton pump inhibitor fails. In PDS, a prokinetic
      is preferred. Second line therapy includes administration of a tricyclic
      antidepressant in low doses, or mirtazapine, but not a selective serotonin
      reuptake inhibitor. 

PMID- 27048252
TI  - Immediate multivessel revascularization may increase cardiac death and myocardial
      infarction in patients with ST-elevation myocardial infarction and multivessel
      coronary artery disease: data analysis from real world practice.
AB  - BACKGROUND/AIMS: The best revascularization strategy for patients with both acute
      ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD)
      is still debatable. We aimed to compare the outcomes of multivessel
      revascularization (MVR) with those of culprit-only revascularization (COR).
      METHODS: A cohort of 215 consecutive patients who had received primary
      angioplasty for STEMI and MVD were divided into two groups according to whether
      angioplasty had been also performed for a stenotic nonculprit artery. The primary
      endpoint was one-year major adverse cardiac events defined as a composite of
      cardiac death, recurrent myocardial infarction, or any repeat revascularization.
      RESULTS: One-year major adverse cardiac events were not significantly different
      between MVR (n = 107) and COR (n = 108) groups. However, the one-year composite
      hard endpoint of cardiac death or recurrent myocardial infarction was notably
      increased in the MVR group compared to the COR group (20.0% vs. 8.9%, p = 0.024).
      In subgroup analysis, the hard endpoint was significantly more frequent in the
      immediate than in the staged MVR subgroup (26.6% vs. 9.8%, p = 0.036). The
      propensity score-matched cohorts confirmed these findings. CONCLUSIONS: In
      patients with STEMI and MVD, MVR, especially immediate MVR with primary
      percutaneous intervention, was not beneficial and led to worse outcomes.
      Therefore, we conclude that COR or staged MVR would be better strategies for
      patients with STEMI and MVD.

PMID- 27048254
TI  - Drug survival and the associated predictors in South Korean patients with
      rheumatoid arthritis receiving tacrolimus.
AB  - BACKGROUND/AIMS: To investigate the drug survival rate of tacrolimus (TAC) and
      analyze the potential predictors of this rate in patients with rheumatoid
      arthritis (RA) in routine care. METHODS2018-01-16: In this retrospective
      longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009
      to January 2014 at a tertiary center in South Korea. The causes of TAC
      discontinuation were classified as lack of efficacy (LOE), adverse events (AEs),
      and others. The drug survival rate was estimated using the Kaplan-Meier method
      and the predictors of this rate were identified by Cox-regression analyses.
      RESULTS: TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2
      , 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%,
      respectively and the median follow-up period from the start of TAC was 32.5
      months. The number of TAC discontinuations due to LOE, AEs, and others were 15
      (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease
      activity was a significant risk factor for TAC discontinuation after adjusting
      for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI],
      1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was
      significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06
      to 11.46; p = 0.039). CONCLUSIONS: In our study, TAC showed a good overall
      survival rate in patients with RA in real clinical practice. This suggests that
      the long-term TAC therapy has a favorable efficacy and safety profile for
      treating RA.

PMID- 27048253
TI  - Clinical outcome of acute nonvariceal upper gastrointestinal bleeding after
      hours: the role of urgent endoscopy.
AB  - BACKGROUND/AIMS: This study was performed to investigate the clinical role of
      urgent esophagogastroduodenoscopy (EGD) for acute nonvariceal upper
      gastrointestinal bleeding (ANVUGIB) performed by experienced endoscopists after
      hours. METHODS: A retrospective analysis was performed for consecutively
      collected data of patients with ANVUGIB between January 2009 and December 2010.
      RESULTS: A total of 158 patients visited the emergency unit for ANVUGIB after
      hours. Among them, 60 underwent urgent EGD (within 8 hours) and 98 underwent
      early EGD (8 to 24 hours) by experienced endoscopists. The frequencies of
      hemodynamic instability, fresh blood aspirate on the nasogastric tube, and high
      risk endoscopic findings were significantly higher in the urgent EGD group.
      Primary hemostasis was achieved in all except two patients. There were nine cases
      of recurrent bleeding, and 30-day mortality occurred in three patients. There
      were no significant differences between the two groups in primary hemostasis,
      recurrent bleeding, and 30-day mortality. In a multiple linear regression
      analysis, urgent EGD significantly reduced the hospital stay compared with early
      EGD. In patients with a high clinical Rockall score (more than 3), urgent EGD
      tended to decrease the hospital stay, although this was not statistically
      significant (7.7 days vs. 12.0 days, p > 0.05). CONCLUSIONS: Urgent EGD after
      hours by experienced endoscopists had an excellent endoscopic success rate.
      However, clinical outcomes were not significantly different between the urgent
      and early EGD groups.

PMID- 27048255
TI  - Caveolin-1 is involved in high glucose accelerated human glomerular mesangial
      cell senescence.
AB  - BACKGROUND/AIMS: We demonstrated the role of caveolin-1 involved in high glucose
      (HG)-induced glomerular mesangial cells (GMCs) senescence. METHODS: HG was used
      to stimulate GMCs. The telomere lengths were analyzed by Southern blot. beta
      Galactosidase staining was determined. The expressions of caveolin-1 and P53
      proteins were determined by Western blot. RESULTS: Treatment with high
      concentrations of glucose induced GMC senescence accompanied by shortened
      telomere length and increase of beta-galactosidase staining as well as P53
      protein, which was abrogated after application of caveolin-1-siRNA. CONCLUSIONS:
      This study proved that HG induced cell senescence in GMCs. The caveolin-1 is
      involved in HG-induced mesangial cell senescence, and blocking caveolin-1
      significantly reduced cell senescence. The effect of caveolin-1 is mediated by
      P53 pathway.

PMID- 27048256
TI  - Association between left ventricular function and paraprotein type in patients
      with multiple myeloma.
AB  - BACKGROUND/AIMS: Multiple myeloma (MM)-associated cardiac damage, particularly
      according to the type of monoclonal (M) protein has not been elucidated. We
      sought to investigate relationship between elevated serum M protein levels and
      echocardiographic indices of cardiac structure and function in patients with MM.
      METHODS: We evaluated a total of 184 consecutive MM patients who underwent
      echocardiography for bone marrow pre-transplant screening. Serum levels of intact
      immunoglobulin M protein and free light chain kappa/lambda (FLC-kappa/-lambda)
      were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM
      (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM,
      significant correlations were found between serum M protein and left atrial
      volume index (LAVi; r = 0.720, p < 0.0001), E/e' (r = 0.511, p < 0.0001), and
      systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with
      LCMM, log-transformed FLC-lambda (log-lambda) was correlated with left
      ventricular ejection fraction (LVEF, r = -0.536, p = 0.010), left ventricular
      (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r
      = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein
      were independent predictors of LAVi in patients with non-LCMM. In patient with
      LCMM, FLC-lambda isotype was only found to be an independent determinant of LVEF.
      CONCLUSIONS: An increase in serum M protein was associated with LV diastolic
      dysfunction, whereas an increase in serum FLC-lambda concentration showed a
      negative correlation with the echocardiographic parameters of LV systolic
      function. These findings also suggest that serum M protein has different effects
      on LV function according to the type of paraproteins in patients with MM.

PMID- 27048257
TI  - Retrospective analysis of palliative chemotherapy for the patients with bladder
      adenocarcinoma: Korean Cancer Study Group Genitourinary and Gynecology Cancer
      Committee.
AB  - BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder
      adenocarcinoma are still unidentified. Therefore, we performed a retrospective
      analysis of the clinical features and chemotherapy outcomes of bladder
      adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were
      initially diagnosed with bladder adenocarcinoma and presented with a clinically
      no other primary site of origin. The collected data included age, gender,
      performance status, stage, hemoglobin, albumin, initial date of diagnosis,
      treatment modality utilized, response to treatment, presence of relapse, last
      status of patient, and last date of follow-up. RESULTS: We retrospectively
      reviewed 29 patients, who were treated with chemotherapy for bladder
      adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median
      age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were
      female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic
      patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f
      luorouracil based chemotherapy, five were gemcitabine based, three were taxane
      and others. Thirteen of them achieved complete response (10.3%) or partial
      response (34.5%). Median progression-free survival (PFS) and overall survival
      (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to
      11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal
      adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046,
      respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed
      moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly
      aggressive form of bladder cancer. PFS and OS were short especially in urachal
      carcinoma.

PMID- 27048258
TI  - The efficacy of daily chlorhexidine bathing for preventing healthcare-associated
      infections in adult intensive care units.
AB  - BACKGROUND/AIMS: Healthcare-associated infections (HAIs) in critically ill
      patients with prolonged length of hospital stay and increased medical costs. The
      aim of this study is to assess whether daily chlorhexidine gluconate (CHG)
      bathing will significantly reduce the rates of HAIs in adult intensive care units
      (ICUs). METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled
      Trials were systematically searched until December 31, 2014 to identify relevant
      studies. Two authors independently reviewed and extracted data from included
      studies. All data was analyzed by Review Manager version 5.3. RESULTS: Fifteen
      studies including three randomized controlled trials and 12 quasi-experimental
      studies were available in this study. The outcomes showed that daily CHG bathing
      were associated with significant reduction in the rates of primary outcomes:
      catheter-related bloodstream infection (risk ratio [RR], 0.44; 95% confidence
      interval [CI], 0.32 to 0.63; p < 0.00001), catheter-associated urinary tract
      infection (RR, 0.68; 95% CI, 0.52 to 0.88; p = 0.004), ventilator-associated
      pneumonia (RR, 0.73; 95% CI, 0.57 to 0.93; p = 0.01), acquisition of methicillin
      resistant Staphylococcus aureus (RR, 0.78; 95% CI, 0.68 to 0.91; p = 0.001) and
      vancomycin-resistant Enterococcus (RR, 0.56; 95% CI, 0.31 to 0.99; p = 0.05).
      CONCLUSIONS: Our study suggests that the use of daily CHG bathing can
      significantly prevent HAIs in ICUs. However, more well-designed studies are
      needed to confirm these findings.

PMID- 27048259
TI  - Actin depolymerization mediated loss of SNTA1 phosphorylation and Rac1 activity
      has implications on ROS production, cell migration and apoptosis.
AB  - Alpha-1-syntrophin (SNTA1) and Rac1 are part of a signaling pathway via the
      dystrophin glycoprotein complex (DGC). Both SNTA1 and Rac1 proteins are over
      expressed in various carcinomas. It is through the DGC signaling pathway that
      SNTA1 has been shown to act as a link between the extra cellular matrix, the
      internal cell signaling apparatus and the actin cytoskeleton. SNTA1 is involved
      in the modulation of the actin cytoskeleton and actin reorganization. Rac1 also
      controls actin cytoskeletal organization in the cell. In this study, we present
      the interplay between f-actin, SNTA1 and Rac1. We analyzed the effect of actin
      depolymerization on SNTA1 tyrosine phosphorylation and Rac1 activity using actin
      depolymerizing drugs, cytochalasin D and latrunculin A. Our results indicate a
      marked decrease in the tyrosine phosphorylation of SNTA1 upon actin
      depolymerization. Results suggest that actin depolymerization mediated loss of
      SNTA1 phosphorylation leads to loss of interaction between SNTA1 and Rac1, with a
      concomitant loss of Rac1 activation. The loss of SNTA1tyrosine phosphorylation
      and Rac1 activity by actin depolymerization results in increased apoptosis,
      decreased cell migration and decreased reactive oxygen species (ROS) levels in
      breast carcinoma cells. Collectively, our results present a possible role of f
      actin in the SNTA1-Rac1 signaling pathway and implications of actin
      depolymerization on cell migration, ROS production and apoptosis.

PMID- 27048260
TI  - Stakeholders' opinions and questions regarding the anticipated malaria vaccine in
      Tanzania.
AB  - BACKGROUND: Within the context of combined interventions, malaria vaccine may
      provide additional value in malaria prevention. Stakeholders' perspectives are
      thus critical for informed recommendation of the vaccine in Tanzania. This paper
      presents the views of stakeholders with regards to malaria vaccine in 12
      Tanzanian districts. METHODS: Quantitative and qualitative methods were employed.
      A structured questionnaire was administered to 2123 mothers of under five
      children. Forty-six in-depth interviews and 12 focus group discussions were
      conducted with teachers, religious leaders, community health workers, health care
      professionals, and scientists. Quantitative data analysis involved frequency
      distributions and cross tabulations using Chi square test to determine the
      association between malaria vaccine acceptability and independent variables.
      Qualitative data were analysed thematically. RESULTS: Overall, 84.2% of the
      mothers had perfect acceptance of malaria vaccine. Acceptance varied
      significantly according to religion, occupation, tribe and region (p < 0.001).
      Ninety two percent reported that they will accept the malaria vaccine despite the
      need to continue using insecticide-treated nets (ITNs), while 88.4% reported that
      they will accept malaria vaccine even if their children get malaria less often
      than non-vaccinated children. Qualitative results revealed that the positive
      opinions towards malaria vaccine were due to a need for additional malaria
      prevention strategies and expectations that the vaccine will reduce visits to the
      health facility, deaths, malaria episodes and treatment-related expenses. Vaccine
      related questions included its side effects, efficacy, protective duration,
      composition, interaction with other medications, provision schedule, availability
      to the pregnant women, mode of administration (oral or injection?) and whether a
      child born of HIV virus or with a chronic illness will be eligible for the
      vaccine? CONCLUSION: Stakeholders had high acceptance and positive opinions
      towards the combined use of the anticipated malaria vaccine and ITNs, and that
      their acceptance remains high even when the vaccine may not provide full
      protection, this is a crucial finding for malaria vaccine policy decisions in
      Tanzania. An inclusive communication strategy should be designed to address the
      stakeholders' questions through a process that should engage and be implemented
      by communities and health care professionals. Social cultural aspects associated
      with vaccine acceptance should be integrated in the communication strategy.

PMID- 27048261
TI  - The characteristics and spatial distributions of initially missed and rebiopsy
      detected prostate cancers.
AB  - PURPOSE: The purpose of this study was to analyze the characteristics of
      initially missed and rebiopsy-detected prostate cancers following 12-core
      transrectal biopsy. METHODS: A total of 45 patients with prostate cancers
      detected on rebiopsy and 45 patients with prostate cancers initially detected on
      transrectal ultrasound-guided biopsy were included in the study. For result
      analysis, the prostate was divided into six compartments, and the cancer positive
      rates, estimated tumor burden, and agreement rates between biopsy and surgical
      specimens, along with clinical data, were evaluated. RESULTS: The largest mean
      tumor burden was located in the medial apex in both groups. There were
      significantly more tumors in this location in the rebiopsy group (44.9%) than in
      the control group (30.1%, P=0.015). The overall sensitivity of biopsy was
      significantly lower in the rebiopsy group (22.5% vs. 43.4%, P<0.001). The
      agreement rate of cancer positive cores between biopsy and surgical specimens was
      significantly lower in the medial apex in the rebiopsy group compared with that
      of the control group (50.0% vs. 65.6%, P=0.035). The cancer positive rates of
      target biopsy cores and premalignant lesions in the rebiopsy group were 63.1% and
      42.3%, respectively. CONCLUSION: Rebiopsy-detected prostate cancers showed
      different spatial distribution and lower cancer detection rate of biopsy cores
      compared with initially diagnosed cancers. To overcome lower cancer detection
      rate, target biopsy of abnormal sonographic findings, premalignant lesions and
      medial apex which revealed larger tumor burden would be recommended when
      performing rebiopsy.

PMID- 27048262
TI  - Older Male Clients of Female Sex Workers in the United States.
AB  - Recent research has provided increased information about the clients of sex
      workers; however, little is known about the population of older male customers
      who contract for heterosexual services online. Clients (N = 208) between 60 and
      84 years of age were obtained through sex work review sites and online discussion
      forums. Participants completed a 129-item questionnaire focusing on physical
      health, sexual and non-sexual behaviors with sex providers, and the qualities
      sought in the same. More than half reported having visited sex providers between
      13 and 24 times or more during the past 12 months. Participants' advancing age
      was positively associated with frequency of paid sex. Most frequent sexual
      activities with providers were fellatio without a condom, followed by penile
      vaginal sex with a condom. Analyses also examine the relationship between aging
      and buying sex. Those with higher incomes and without spouses or partners were
      more likely to report non-sexual activities with providers, and many participants
      sought a "GFE" or girlfriend experience, in which paid sexual exchanges are part
      of a relationship that mirrors conventional non-remunerative relationships.

PMID- 27048263
TI  - Capsular hook-assisted implantation of modified capsular tension ring.
AB  - A 16-year-old boy presented with decrease of vision over a period of 2 years. On
      examination, he was diagnosed to have microspherophakia with lenticular myopia
      with secondary glaucoma in both eyes. He was treated by lens aspiration and two
      point capsular support using a modified capsular tension ring (M-CTR) and
      capsular tension segment (CTS) sutured to the sclera along with implantation of a
      foldable intraocular lens inside the bag. Lens aspiration was performed without
      artificial capsular hook support of the bag, as the lens was soft and vitreous
      was formed. However, M-CTR rotation into the bag was fraught with repeated
      adherence of the advancing end of the M-CTR into the loose bag causing
      simultaneous rotation of the bag with the rotation of the ring resulting in
      transient increase in bag subluxation. Capsular hooks provided appropriate
      countertraction to the unsupported bag, thus facilitating easy insertion and
      rotation of the ring into the bag.

PMID- 27048264
TI  - Dealing with the complex dynamics of teaching hospitals.
AB  - Innovation and change in postgraduate medical education programs affects teaching
      hospital organizations, since medical education and clinical service are
      interrelated.Recent trends towards flexible, time-independent and individualized
      educational programs put pressure on this relationship. This pressure may lead to
      organizational uncertainty, unbalance and friction making it an important issue
      to analyze.The last decade was marked by a transition towards outcome-based
      postgraduate medical education. During this transition competency-based programs
      made their appearance. Although competency-based medical education has the
      potential to make medical education more efficient, the effects are still under
      debate. And while this debate continues, the field of medical education is
      already introducing next level innovations: flexible and individualized training
      programs. Major organizational change, like the transition to flexible education
      programs, can easily lead to friction and conflict in teaching hospital
      organizations.This article analyses the organizational impact of postgraduate
      medical education innovations, with a particular focus on flexible training and
      competency based medical education. The characteristics of teaching hospital
      organizations are compared with elements of innovation and complexity theory.With
      this comparison the article argues that teaching hospital organizations have
      complex characteristics and behave in a non-linear way. This perspective forms
      the basis for further discussion and analysis of this unexplored aspect of
      flexible and competency based education. 

PMID- 27048265
TI  - Beliefs about dangerousness of people with mental health problems: the role of
      media reports and personal exposure to threat or harm.
AB  - PURPOSE: To assess the associations between beliefs about the dangerousness of
      people with mental health problems and exposure to media reports of violence or
      personal experiences of fear, threat or harm. METHODS: Telephone interviews were
      carried out with 5220 Australians aged 18+. Respondents heard a vignette of a
      person with depression or early schizophrenia and were asked whether they
      believed him to be dangerous. Other questions covered past 12-month recall of
      media reports of violence and mental health problems, contact with and
      experiences of fear, threat or harm by people with mental health problems.
      Multinomial logistic regression was used to assess the associations between
      beliefs about dangerousness and media and these types of contact with people with
      mental health problems. RESULTS: For the early schizophrenia vignette, recall of
      media reports and having felt afraid of someone were associated with beliefs
      about dangerousness. For the depression vignette, media reports about violence
      and mental health problems or the experiences of feeling afraid or having been
      threatened or harmed were not strongly associated with beliefs about
      dangerousness. For both vignettes, knowing someone with a mental health problem
      and having a higher level of education were associated with less belief in
      dangerousness. CONCLUSIONS: Media reports may play a greater role in forming
      attitudes in low prevalence disorders and further efforts to reduce any adverse
      impact of media reporting should focus on these disorders. The study also
      supports the effectiveness of contact with people with mental health problems in
      reducing beliefs about dangerousness.

PMID- 27048266
TI  - The role of surgical expertise with regard to chronic postoperative inguinal pain
      (CPIP) after Lichtenstein correction of inguinal hernia: a systematic review.
AB  - OBJECTIVE: The aim of this study was to evaluate whether a relation exists
      between surgical expertise and incidence of chronic postoperative inguinal pain
      (CPIP) after inguinal hernia repair using the Lichtenstein procedure .
      BACKGROUND: CPIP after inguinal hernia repair remains a major clinical problem
      despite many efforts to address this problem. Recently, case volume and
      specialisation have been found correlated to significant improvement of outcomes
      in other fields of surgery; to date these important factors have not been
      reviewed extensively enough in the context of inguinal hernia surgery. METHODS: A
      systematic literature review was performed to identify randomised controlled
      trials reporting on the incidence of CPIP after the Lichtenstein procedure and
      including the expertise of the surgeon. Surgical expertise was subdivided into
      expert and non-expert. RESULTS: In a total of 16 studies 3086 Lichtenstein
      procedures were included. In the expert group the incidence of CPIP varied
      between 6.9 and 11.7 % versus an incidence of 18.1 and 39.4 % in the non-expert
      group. Due to the heterogeneity between groups no statistical significance could
      be demonstrated. CONCLUSION: The results of this evaluation suggest that an
      association between surgical expertise and CPIP is highly likely warranting
      further analysis in a prospectively designed study.

PMID- 27048268
TI  - Multivariate Gene-Based Association Test on Family Data in MGAS.
AB  - In analyses of unrelated individuals, the program multivariate gene-based
      association test by extended Simes (MGAS), which facilitates multivariate gene
      based association testing, was shown to have correct Type I error rate and
      superior statistical power compared to other multivariate gene-based approaches.
      Here we show, through simulation, that MGAS can also be applied to data including
      genetically related subjects (e.g., family data), by using p value information
      obtained in Plink or in generalized estimating equations (with the 'exchangeable'
      working correlation matrix), both of which account for the family structure on a
      univariate single nucleotide polymorphism-based level by applying a sandwich
      correction of standard errors. We show that when applied to family-data, MGAS has
      correct Type I error rate, and given the details of the simulation setup,
      adequate power. Application of MGAS to seven eye measurement phenotypes showed
      statistically significant association with two genes that were not discovered in
      previous univariate analyses of a composite score. We conclude that MGAS is a
      useful and convenient tool for multivariate gene-based genome-wide association
      analysis in both unrelated and related individuals.

PMID- 27048267
TI  - Impact of 24 months of anti-TNF therapy versus methotrexate on body weight in
      patients with rheumatoid arthritis: a prospective observational study.
AB  - To evaluate the impact of anti-TNF-alpha therapy on the body weight of rheumatoid
      arthritis (RA) patients following 24 months of treatment. Data were collected on
      all RA patients included in the Veneto Region's Registry of Biological Therapy
      from January 2007 to July 2012. Inclusion criteria were: start of monotherapy
      with adalimumab, etanercept, or methotrexate, no previous use of biologic
      therapy, and at least 24 months of treatment. At baseline, 12, and 24 months,
      each patient completed a questionnaire about physical activity, smoking, alcohol,
      and food habits. One hundred and thirty-one RA patients in monotherapy with
      etanercept (n = 47), adalimumab (n = 44), and methotrexate (n = 40) were enrolled
      for this study. After 24 months of therapy, there was an increase of weight only
      in patients treated with anti-TNF-alpha. Patients on etanercept and adalimumab
      therapy showed a risk to gain weight six times greater compared to those on
      methotrexate therapy. The results of present study show that the use of anti-TNF
      alpha in RA patients can be associated to a significant increase of body weight.
      This increase is not shown in patients under treatment with methotrexate. A more
      careful evaluation of weight changes needs to be considered in RA patients under
      anti-TNF-alpha treatment. 

PMID- 27048269
TI  - Systolic Time Intervals and New Measurement Methods.
AB  - Systolic time intervals have been used to detect and quantify the directional
      changes of left ventricular function. New methods of recording these cardiac
      timings, which are less cumbersome, have been recently developed and this has
      created a renewed interest and novel applications for these cardiac timings. This
      manuscript reviews these new methods and addresses the potential for the
      application of these cardiac timings for the diagnosis and prognosis of different
      cardiac diseases.

PMID- 27048270
TI  - Simplified anal sphincter anatomy.

PMID- 27048271
TI  - Recent Developments in Group I Metabotropic Glutamate Receptor Allosteric
      Modulators for the Treatment of Psychiatric and Neurological Disorders (2014-May
      2015).
AB  - In the last ~30 years, scientists have made great strides in understanding the
      biological function of group I metabotropic glutamate receptors (mGlu) in health
      and disease, as well as developing a broad array of potent and selective agents
      able to activate or inhibit these receptors. This article provides a
      comprehensive review of the most recent group I mGlu modulators published in
      patent and non-patent literatures from 2014 to May, 2015, including design,
      structure-activity relationship, in silico, in vitro and in vivo properties of
      key compounds. The current status of clinical mGlu5 negative allosteric
      modulators (NAMs) and the development of mGlu1 and mGlu5 PET ligands are also
      highlighted. While the therapeutic potential for group I mGlu modulating agents
      appears high, significant challenges remain. Strategies to reduce clinical
      development risks and mitigate important side effects, including psychotomimetic
      events observed with several mGlu5 NAMs and cellular toxicity associated with
      mGlu5 positive allosteric modulators (PAMs), while retaining therapeutic efficacy
      through approaches such as biased ligand signaling are discussed.

PMID- 27048272
TI  - Inhibitors of Glycine Transporter-1: Potential Therapeutics for the Treatment of
      CNS Disorders.
AB  - Glycine acts as an inhibitory neurotransmitter at glycine receptor (GlyR)
      enriched synapses and as an obligatory co-agonist at the N-methyl-D-aspartate
      (NMDA) receptor, where it facilitates neuronal excitation. Two high-affinity and
      substrate selective transporters, glycine transporter-1 and glycine transporter-2
      (GlyT-1 and GlyT-2), regulate extracellular glycine concentrations within the CNS
      and as such, play critical roles in maintaining a balance between inhibitory and
      excitatory neurotransmission. GlyT-1 inhibition has been extensively examined as
      a potential means by which to treat several CNS disorders that include
      schizophrenia, depression, anxiety, obsessive compulsive disorder (OCD), and
      addiction. More recently, preclinical studies have emerged that indicate the
      approach may also promote neuroprotection, provide a pharmacotherapeutic strategy
      for autism spectrum disorders (ASDs), and treat symptomology associated with
      pain, Parkinson's disease, and epilepsy. This review examines the pharmacological
      aspects of GlyT-1 inhibition and describes drug discovery and development efforts
      toward the identification of novel inhibitors.

PMID- 27048273
TI  - Comparison of mid-term haemodynamic performance between the BioValsalva and the
      BioIntegral valved conduits after aortic root replacement.
AB  - OBJECTIVES: We retrospectively compared the haemodynamic performance of the
      BioValsalva (BV) and BioIntegral (BI) biological aortic-valved conduits in the
      aortic root position. METHODS: Between July 2008 and June 2014, a total of 55
      patients underwent aortic root replacement using the BV conduit (n = 27) or the
      BI conduit (n = 28). The primary study endpoints were haemodynamic performance
      during follow-up, including mean pressure gradients (MPGs) and effective orifice
      areas (EOAs). Secondary study endpoints were early postoperative outcomes within
      30 days and survival. RESULTS: Both groups did not differ in regard to
      demographics (BV: median age 71 years, 70.4% female; BI: median age 66 years,
      85.7% female, P = 0.15 and P = 0.17) and risk profile (median EuroSCORE-II BV:
      3.8 vs 5.3% for BI, P = 0.38). A total of 20% of the total patients (BV 5/27,
      18.5% vs BI 6/28, 21.4%) presented with acute type-A aortic dissection. During
      follow-up, both groups showed no difference in MPGs for all valve sizes [BV, 11.0
      mmHg (8.3-14.8 mmHg) vs BI, 11.5 mmHg (9.0-13.0), P = 0.82]. Similar results were
      achieved for EOAs for all valve sizes [BV, 1.85 cm(2) (1.55-2.21) vs BI, 1.80
      cm(2) (1.64-1.83), P = 0.24]. Moreover, there was no statistically significant
      difference in aortic regurgitation (AR) with none/trace AR in (21/23) 91.3% in BV
      patients versus (16/21) 76.2% in BI patients (P = 0.23) at follow-up. Both groups
      showed a high rate of concomitant procedures (BV: 59.3% vs BI: 71.4%, P = 0.40)
      and emergency indication (BV: 18.5% vs BI: 21.4%, P = 0.79), resulting in an
      overall 30-day mortality rate of 7.3% (4/55 patients). CONCLUSIONS: The present
      small single-centre study is one of the first to evaluate and compare the
      BioValsalva and BioIntegral biological aortic-valved conduit in the aortic root
      position. Both conduits showed optimal haemodynamic results with a low incidence
      of aortic regurgitation.

PMID- 27048274
TI  - Have Socioeconomic Inequalities in Tobacco Use in India Increased Over Time?
      Trends From the National Sample Surveys (2000-2012).
AB  - INTRODUCTION: India has experienced marked sociocultural change, economic growth
      and industry promotion of tobacco products over the past decade. Little is known
      about the influence of these factors on socioeconomic patterning of tobacco use.
      This study examines trends in tobacco use by socioeconomic status (SES) in India
      between 2000 and 2012. METHODS: We analyzed data in 2014 from nationally
      representative repeated cross-sectional National Sample Surveys (NSS) in India
      for 1999-2000, 2004-2005 and 2011-2012 (n = 346 612 households). Prevalence and
      volume trends in cigarette, "bidi" and smokeless tobacco use were examined by
      household expenditure, educational attainment and caste/tribe status using Two
      part model. RESULTS: Prevalence of any tobacco use remained consistent in the
      poorest households (61.5% to 62.7%) and declined among the richest (43.8% to
      36.8%) between 2000-2012. Bidi use declined across all groups (poorest: 26.3% to
      16.8%, richest: 19.8% to 10.7%) while cigarette use increased (poorest: 1.2% to
      1.3%, richest: 6.5% to 7.0%). Relative to educated and general caste households,
      between 2000 and 2012 cigarette use in illiterate households increased by 38% and
      among Scheduled Tribe households increased by 32%. Smokeless tobacco use
      increased for all households (poorest: 26.2% to 33.9%, richest: 11.4% to 13.5%,
      Scheduled Tribe: 31.1% to 34.8%, general caste: 13.6% to 18.5%), with greater
      increases among richer, more educated and general caste households. CONCLUSION:
      Marked SES patterning of tobacco use has persisted in India. Improving
      enforcement of tobacco control policies and monitoring comprehensive smoke-free
      legislations are needed to address this growing burden. IMPLICATIONS: We found
      "resilient" tobacco patterns in the last decade despite prevention interventions.
      SES continues to be inversely associated with tobacco products, with the
      exception of cigarettes. The declines in bidi use may be getting replaced by
      increase in cigarette use trends, especially among lower SES groups. The use of
      smokeless tobacco products has increased across all SES groups and the volume of
      smokeless tobacco use is not been declining despite a number of policies on
      tobacco use. This may be attributed to inadequate attention to chewed forms of
      tobacco in current policies, particularly to implementing pictoral warnings and
      regulating surrogate advertising. Evaluating the implementation of anti-tobacco
      policies and ensuring equity dimensions in interventions is urgently needed to
      address tobacco use inequalities.

PMID- 27048275
TI  - Effects of Fixed Orthodontic Treatment Using Conventional, Copper-Included, and
      Epoxy-Coated Nickel-Titanium Archwires on Salivary Nickel Levels: A Double-Blind
      Randomized Clinical Trial.
AB  - Orthodontic archwires, especially nickel-titanium (NiTi) ones, are a major source
      of nickel release. Despite their importance, no in vivo studies have assessed the
      ion release from conventional or new generations of NiTi archwires (copper
      included and epoxy-coated). This double-blind parallel randomized clinical trial
      was done on 84 saliva specimens sampled at two time points from 42 orthodontic
      patients. The patients were randomly divided into three groups of NiTi, copper
      NiTi (NiTiCu), and epoxy NiTi archwires (n = 14 each). The effects of 2-month
      treatment, wire types, gender, and age on pretreatment, posttreatment, and time
      dependent differences were analyzed statistically (alpha = 0.05). Salivary nickel
      concentrations were 10.4571 +/- 0.77168 and 11.0779 +/- 0.81232 MUg/L,
      respectively, in the baseline and second month. This increase was significant (P
      = 0.0000, paired t test). The extents of nickel increase in different groups were
      0.8279 +/- 0.14 (NiTi), 0.6493 +/- 0.10 (NiTiCu), and 0.385 +/- 0.11 (epoxy
      coated NiTi) MUg/L (P = 0.0000, one-way analyses of variance (ANOVA)).
      Differences between each two archwire types were significant (P = 0.000, Tukey).
      Age and gender did not play a role. It can be concluded that NiTi archwires might
      increase nickel salivary levels. Epoxy-coated NiTi followed by copper NiTi
      archwires might release less nickel compared to conventional NiTi ones.

PMID- 27048276
TI  - Influence of Primary Ligands (ODA, TDA) on Physicochemical and Biological
      Properties of Oxidovanadium (IV) Complexes with Bipy and Phen as Auxiliary
      Ligands.
AB  - The influence of the oxydiacetate (ODA) and thiodiacetate (TDA) ligands on the
      physicochemical and biological properties of the oxidovanadium(IV) ternary
      complexes of the VO(L)(B) type, where L denotes ODA or TDA and B denotes 2,2'
      bipyridine (bipy) or 1,10-phenanthroline (phen), has been investigated. The
      stability of the complexes in aqueous solutions, assessed based on the
      potentiometric titration method, increases in the following direction:
      VO(TDA)(bipy) < VO(ODA)(bipy) < VO(TDA)(phen) < VO(ODA)(phen). Furthermore, the
      influence of the TDA and ODA ligands on the antioxidant activity of the
      oxidovanadium(IV) complexes toward superoxide free radical (O2*-), 2,2'
      azinobis(3-ethylbenzothiazoline-6 sulfonic acid) cation radical (ABTS+*) and 2,2
      diphenyl-1-picrylhydrazyl radical (DPPH*) has been examined and discussed. The
      reactivity of the complexes toward O2*- increases in the following direction:
      VO(TDA)(phen) < VO(TDA)(bipy) ~ VO(ODA)(bipy) < VO(ODA)(phen). The antioxidant
      activity against ABTS+* and DPPH* free radicals is higher for phen complexes,
      whereas the thiodiacetate complexes are more reactive than are the corresponding
      oxydiacetate ones. Finally, herein, the cytoprotective activity of the complexes
      against the oxidative damage generated exogenously by hydrogen peroxide in the
      hippocampal neuronal HT22 cell line (the MTT and LDH tests) is reported. In a low
      concentration (1 MUM), the cytoprotective action of thiodiacetate complexes is
      much higher than that of the corresponding oxydiacetate complexes. However, in
      the higher concentration range (10 and 100 MUM), the antioxidant activity of the
      complexes is overcompensated by their cytotoxic effect.

PMID- 27048277
TI  - Hybolites Revisited.
AB  - BACKGROUND: Hyperstructures are large assemblies of molecules and macromolecules
      that perform functions such as metabolism (including RNA and protein synthesis
      and degradation), transport, DNA replication, cell division, signalling and
      chemotaxis. METHODS: Such hyperstructures might be manipulated by hybrid
      metabolites or hybolites made by a pairwise, covalently linked combination of the
      thousands of small molecules involved in metabolism and signalling. RESULTS:
      Here, we review recent evidence for hyperstructures in prokaryotes and for
      interactions between hyperstructures as a determinant of the phenotype. We also
      mention extending hybolite therapy to eukaryotes, consider new designs for
      hybolites, and discuss relevant patents.

PMID- 27048278
TI  - The Influence of Soil Characteristics on the Toxicity of Oil Refinery Waste for
      the Springtail Folsomia candida (Collembola).
AB  - We determined the toxicity of oil refinery waste in three soils using the
      springtail Folsomia candida (Collembola) in bioassays. Sublethal exposure to a
      concentration series of API-sludge presented EC50's for reproduction of 210 mg/kg
      in site soil; 880 mg/kg in LUFA2.2- and 3260 mg/kg in OECD-soil. The sludge was
      the least toxic in the OECD-soil with the highest clay and organic matter
      content, the highest maximum water holding capacity, and the least amount of
      sand. It was the most toxic in the reference site soil with the lowest organic
      matter content and highest sand content. The results emphasized the important
      role of soil characteristics such as texture and organic matter content in
      influencing toxicity, possibly by affecting bioavailability of toxicants. 

PMID- 27048279
TI  - A case of liver cirrhosis with bleeding from stomal varices successfully treated
      using balloon-occluded retrograde transvenous obliteration.
AB  - A 66-year-old male patient with liver cirrhosis because of alcohol intake
      underwent a Hartmann's procedure for rectal cancer. Four months later, bleeding
      from the sigmoid stoma occurred and persisted for 2 months. A colonoscopic
      examination revealed bleeding from stomal varices. Three-dimensional computed
      tomography (CT) imaging demonstrated the inferior mesenteric vein and left
      superficial epigastric vein as the feeding and drainage vessels, respectively.
      Balloon-occluded retrograde transvenous obliteration (B-RTO) through the left
      epigastric vein was performed using a microballoon catheter inserted from the
      right femoral vein according to the Seldinger method. A CT examination performed
      2 days after the B-RTO procedure revealed that the blood flow had disappeared,
      with thrombosis formation in both the stomal varices and the feeding vein. No
      recurrent bleeding from the stoma occurred. B-RTO using a microballoon catheter
      is useful as a therapeutic procedure for stomal varices to prevent bleeding,
      since the procedure can be performed with minimal invasion using the Seldinger
      method. 

PMID- 27048281
TI  - Spinal near-infrared spectroscopy monitoring in aortic surgery: the beginning of
      understanding it or already clinical routine?

PMID- 27048280
TI  - Effectiveness, cost effectiveness, acceptability and implementation
      barriers/enablers of chronic kidney disease management programs for Indigenous
      people in Australia, New Zealand and Canada: a systematic review of mixed
      evidence.
AB  - BACKGROUND: Indigenous peoples in Australia, New Zealand and Canada carry a
      greater burden of chronic kidney disease (CKD) than the general populations in
      each country, and this burden is predicted to increase. Given the human and
      economic cost of dialysis, understanding how to better manage CKD at earlier
      stages of disease progression is an important priority for practitioners and
      policy-makers. A systematic review of mixed evidence was undertaken to examine
      the evidence relating to the effectivness, cost-effectiveness and acceptability
      of chronic kidney disease management programs designed for Indigenous people, as
      well as barriers and enablers of implementation of such programs. METHODS:
      Published and unpublished studies reporting quantitative and qualitative data on
      health sector-led management programs and models of care explicitly designed to
      manage, slow progression or otherwise improve the lives of Indigenous people with
      CKD published between 2000 and 2014 were considered for inclusion. Data on
      clinical effectiveness, ability to self-manage, quality of life, acceptability,
      cost and cost-benefit, barriers and enablers of implementation were of interest.
      Quantitative data was summarized in narrative and tabular form and qualitative
      data was synthesized using the Joanna Briggs Institute meta-aggregation approach.
      RESULTS: Ten studies were included. Six studies provided evidence of clinical
      effectiveness of CKD programs designed for Indigenous people, two provided
      evidence of cost and cost-effectiveness of a CKD program, and two provided
      qualitative evidence of barriers and enablers of implementation of effective
      and/or acceptable CKD management programs. Common features of effective and
      acceptable programs were integration within existing services, nurse-led care,
      intensive follow-up, provision of culturally-appropriate education, governance
      structures supporting community ownership, robust clinical systems supporting
      communication and a central role for Indigenous Health Workers. CONCLUSIONS:
      Given the human cost of dialysis and the growing population of people living with
      CKD, there is an urgent need to draw lessons from the available evidence from
      this and other sources, including studies in the broader population, to better
      serve this population with programs that address the barriers to receiving high
      quality care and improve quality of life.

PMID- 27048282
TI  - School-based intervention to enable school children to act as change agents on
      weight, physical activity and diet of their mothers: a cluster randomized
      controlled trial.
AB  - BACKGROUND: School health promotion has been shown to improve the lifestyle of
      students, but it remains unclear whether school-based programs can influence
      family health. We developed an innovative program that enables school children to
      act as change agents in promoting healthy lifestyles of their mothers. The
      objective of this study was to examine the effect of the child-initiated
      intervention on weight, physical activity and dietary habit of their mothers.
      METHODS: A 12-month cluster randomized trial was conducted, with school as a
      cluster. Participants were mothers with grade 8 students, aged around 13 years,
      of 20 schools in Homagama, Sri Lanka. Students of the intervention group were
      trained by facilitators to acquire the ability to assess noncommunicable disease
      risk factors in their homes and take action to address them, whereas those of the
      comparison group received no intervention. Body weight, step count and lifestyle
      of their mothers were assessed at baseline and post-intervention. Multi-level
      multivariable linear regression and logistic regression were used to assess the
      effects of intervention on continuous and binary outcomes, respectively. RESULTS:
      Of 308 study participants, 261 completed the final assessment at 12 month. There
      was a significantly greater decrease of weight and increase of physical activity
      in the intervention group. The mean (95% confidence interval) difference
      comparing the intervention group with the control group was -2.49 (-3.38 to 
      1.60) kg for weight and -0.99 (-1.40 to -0.58) kg/m(2) for body mass index. The
      intervention group had a 3.25 (95% confidence interval 1.87-5.62) times higher
      odds of engaging in adequate physical activity than the control group, and the
      former showed a greater number of steps than the latter after intervention. The
      intervention group showed a greater reduction of household purchase of biscuits
      and ice cream. CONCLUSIONS: A program to motivate students to act as change
      agents of family's lifestyle was effective in decreasing weight and increasing
      physical activity of their mothers. TRIAL REGISTRATION: Sri Lanka Clinical Trials
      Registry SLCTR/2013/011 .

PMID- 27048283
TI  - European Society of Endocrinology Clinical Practice Guideline for long-term
      follow-up of patients operated on for a phaeochromocytoma or a paraganglioma.
AB  - Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours.
      Standard treatment is surgical resection. Following complete resection of the
      primary tumour, patients with PPGL are at risk of developing new tumoural events.
      The present guideline aims to propose standardised clinical care of long-term
      follow-up in patients operated on for a PPGL. The guideline has been developed by
      The European Society of Endocrinology and based on the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) principles. We performed a
      systematic review of the literature and analysed the European Network for the
      Study of Adrenal Tumours (ENS@T) database. The risk of new events persisted in
      the long term and was higher for patients with genetic or syndromic diseases.
      Follow-up in the published cohorts and in the ENS@T database was neither
      standardised nor exhaustive, resulting in a risk of follow-up bias and in low
      statistical power beyond 10 years after complete surgery. To inform patients and
      care providers in this context of low-quality evidence, the Guideline Working
      Group therefore prepared recommendations on the basis of expert consensus. Key
      recommendations are the following: we recommend that all patients with PPGL be
      considered for genetic testing; we recommend assaying plasma or urinary
      metanephrines every year to screen for local or metastatic recurrences or new
      tumours; and we suggest follow-up for at least 10 years in all patients operated
      on for a PPGL. High-risk patients (young patients and those with a genetic
      disease, a large tumour and/or a paraganglioma) should be offered lifelong annual
      follow-up.

PMID- 27048284
TI  - Assessing Acceptability of Self-Sampling Kits, Prevalence, and Risk Factors for
      Human Papillomavirus Infection in American Indian Women.
AB  - We evaluated the feasibility and acceptability of self-sampling for human
      papillomavirus (HPV) testing and calculated the prevalence of and risk factors
      for high-risk (hr) HPV infections in a community-based sample of American Indian
      women. To this end, we recruited 329 Hopi women aged 21-65 years to self-collect
      vaginal samples for hrHPV testing. Samples were tested by polymerase chain
      reaction for 14 hrHPV genotypes. We used Chi square tests to identify correlates
      of preference for clinician Pap testing versus HPV self-sampling, and age
      adjusted Poisson regression to evaluate correlates of hrHPV prevalence. We found
      that satisfaction with HPV self-sampling was high, with 96 % of women reporting
      that the sample was easy to collect and 87 % reporting no discomfort. The
      majority (62 %) indicated that they preferred HPV self-sampling to receiving a
      Pap test from a clinician. Preference for Pap testing over HPV self-sampling was
      positively associated with adherence to Pap screening and employment outside the
      home. All samples evaluated were satisfactory for HPV testing, and 22 % were
      positive for hrHPV. HrHPV prevalence peaked in the late 20 s and declined with
      increasing age. HrHPV positivity was inversely associated with having children
      living the household. In conclusion, HPV self-sampling is feasible and acceptable
      to Hopi women, and could be effective in increasing rates of cervical cancer
      screening in Hopi communities. HrHPV prevalence was similar to estimates in the
      general United States population.

PMID- 27048285
TI  - Impact of X-linked inhibitor of apoptosis protein on survival of nasopharyngeal
      carcinoma patients following radiotherapy.
AB  - This study aims to investigate CNE1 and CNE2 cell proliferation and apoptosis of
      nasopharyngeal cancer (NPC) and X-linked inhibitor of apoptosis protein (XIAP)
      expression in NPC patients after radiotherapy. Quantitative real-time
      quantitative polymerase chain reaction (qRT-PCR) and Western Blot detected XIAP
      and XIAP-associated factor1 (XAF1) messenger RNA (mRNA) and protein expression of
      CNE1 and CNE2 in NPC cells irradiated by gamma-ray; MTT and flow cytometry assays
      detected CNE2 cells proliferation and apoptotic rate, respectively. With a
      retrospective analysis of 109 NPC patients in Xinxiang Central Hospital,
      immunohistochemistry (IHC) method detected XIAP expression, followed by a 5-year
      clinical analysis of the prognosis relevance after radiotherapy. In vitro, the
      inhibition and apoptotic rates of cells increased with the growth of radiation
      dose. qRT-PCR and Western blot detection declared that XIAP mRNA and protein
      expression increased, whereas XAF1 mRNA and protein expression decreased with the
      growth of radiation dose and exposure time. And XIAP mRNA and protein expression
      were negatively correlated with proliferation and apoptotic rates of the cells.
      In vivo, positive XIAP expression rate was negatively correlated with
      pathological tumor-node-metastasis (p-TNM) staging and tumor differentiation.
      Further, high XIAP expression, high p-TNM staging, and lower degree of
      differentiation were significantly correlated with the decrease of NPC patients'
      survival rate. Additionally, XIAP expression, p-TNM staging, and degrees of
      differentiation were independent risk factors for the survival of the NPC
      patients after radiotherapy. Increased XIAP expression and decreased XAF1
      expression may be one reason for the apoptosis delays of CNE1 and CNE2 cells
      after irradiation, and the XIAP expression or the p-TNM staging and degree of
      differentiation are independent risk factors for NPC patients' survival after
      radiotherapy, providing a molecular rationale for radiotherapy and prognosis of
      NPC.

PMID- 27048286
TI  - Inhibition of protein methylesterase 1 decreased cancerous phenotypes in
      endometrial adenocarcinoma cell lines and xenograft tumor models.
AB  - Protein methylesterase 1 (PME-1) promotes cancerous phenotypes through the
      demethylation and inactivation of protein phosphatase 2A. We previously
      demonstrated that PME-1 overexpression promotes Akt, ERK, and may promote Wnt
      signaling and increases tumor burden in a xenograft model of endometrial cancer.
      Here, we show that covalent PME-1 inhibitors decrease cell proliferation and
      invasive growth in vitro but have no effect in vivo at the concentrations tested;
      however, depletion of PME-1 with shRNA in an endometrial cancer xenograft model
      significantly reduced tumor growth. Thus, discovery of more potent PME-1
      inhibitors may be beneficial for the treatment of endometrial cancer.

PMID- 27048287
TI  - Evidence for embryonic stem-like signature and epithelial-mesenchymal transition
      features in the spheroid cells derived from lung adenocarcinoma.
AB  - Identification of the cellular and molecular aspects of lung cancer stem cells
      (LCSCs) that are suggested to be the main culprit of tumor initiation,
      maintenance, drug resistance, and relapse is a prerequisite for targeted therapy
      of lung cancer. In the current study, LCSCs subpopulation of A549 cells was
      enriched, and after characterization of the spheroid cells, complementary DNA
      (cDNA) microarray analysis was applied to identify differentially expressed genes
      (DEGs) between the spheroid and parental cells. Microarray results were validated
      using quantitative real-time reverse transcription-PCR (qRT-PCR), flow cytometry,
      and western blotting. Our results showed that spheroid cells had higher
      clonogenic potential, up-regulation of stemness gene Sox2, loss of CD44
      expression, and gain of CD24 expression compared to parental cells. Among a total
      of 160 genes that were differentially expressed between the spheroid cells and
      the parental cells, 104 genes were up-regulated and 56 genes were down-regulated.
      Analysis of cDNA microarray revealed an embryonic stem cell-like signature and
      over-expression of epithelial-mesenchymal transition (EMT)-associated genes in
      the spheroid cells. cDNA microarray results were validated at the gene expression
      level using qRT-PCR, and further validation was performed at the protein level by
      flow cytometry and western blotting. The embryonic stem cell-like signature in
      the spheroid cells supports two important notions: maintenance of CSCs phenotype
      by dedifferentiating mechanisms activated through oncogenic pathways and the
      origination of CSCs from embryonic stem cells (ESCs). PI3/AKT3, as the most
      common up-regulated pathway, and other pathways related to aggressive tumor
      behavior and EMT process can confer to the spheroid cells' high potential for
      metastasis and distant seeding.

PMID- 27048289
TI  - Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.
AB  - In the mammary glands of lactating animals, the mammary epithelial cells that
      surround the lumen of the acini produce and secrete copious amounts of milk.
      Functional differentiation of these mammary epithelial cells depends on the
      development of high-efficiency secretory pathways, notably for protein and lipid
      secretion. Protein secretion is a fundamental process common to all animal cells
      that involves a subset of cellular organelles, including the endoplasmic
      reticulum and the Golgi apparatus. In contrast, en masse secretion of
      triglycerides and cholesterol esters in the form of milk fat globules is a unique
      feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the
      intracellular precursors of milk fat globules, originate from the endoplasmic
      reticulum, as do most milk-specific proteins. This organelle is therefore pivotal
      in the biogenesis of milk components. Fractionation of the cell into its
      subcellular parts is an approach that has proven very powerful for understanding
      organelle function and for studying the specific role of an organelle in a given
      cell activity. Here we describe a method for the purification of both smooth and
      rough microsomes, the membrane-bound endoplasmic reticulum fragments that form
      from endoplasmic reticulum domains when cells are broken up, from mammary gland
      tissue at lactation.

PMID- 27048288
TI  - Spousal migration and human papillomavirus infection among women in rural western
      Nepal.
AB  - BACKGROUND: In April 2014 we investigated the association of migration of a
      woman's husband with her high-risk human papillomavirus (HR-HPV) infection status
      and her abnormal cervical cytology status in the Achham district of rural Far
      Western Nepal. METHODS: Women were surveyed and screened for HR-HPV during a
      health camp conducted by the Nepal Fertility Care Center. Univariate and
      multivariable statistical tests were performed to determine the association of a
      husband's migration status with HR-HPV infection and cervical cytology status.
      RESULTS: In 265 women, the prevalence of HR-HPV was 7.5% (20/265), while the
      prevalence of abnormal cervical cytology, defined using the Bethesda system as
      atypical glandular cells of undetermined significance or worse, was 7.6%
      (19/251). Half of the study participants (50.8%, 130/256) had husbands who had
      reported migrating for work at least once. Women aged <=34 years were
      significantly less likely to test positive for HR-HPV than women aged >34 years
      (OR 0.22, 95% CI 0.07 to 0.71). HR-HPV infection and abnormal cervical cytology
      status were not directly associated with a husband's migration. CONCLUSION: Older
      women were found to have a higher prevalence of HPV than younger women. It is
      possible that a husband's migration for work could be delaying HR-HPV infections
      in married women until an older age.

PMID- 27048290
TI  - A fast and stable vascular deformation scheme for interventional surgery training
      system.
AB  - BACKGROUND: The emergence and development of robot assistant interventional
      vascular surgery technologies have benefited many patients with cardiovascular or
      cerebrovascular diseases. Due to the absence of effective training measures,
      these new advanced technologies have not been fully utilized and only few
      experienced surgeons can perform such complicated surgeries so far. In order to
      solve such problems, virtual reality based vascular interventional surgery
      training system, a promising way to train young surgeons or assist experienced
      surgeons to perform surgery, has been widely studied. METHODS: In this paper, we
      mainly conduct a thorough study on both reliable deformation and high real-time
      performance of an interactive surgery training system. An efficient hybrid
      geometric blood vessel model which handles the collision detection query and
      vascular deformation calculation separately is employed to enhance the real-time
      performance of our surgery training system. In addition, a position-based dynamic
      approach with volume conservation constraint is used to improve the vascular
      deformation result. Finally, a hash table based spatial adaptive acceleration
      algorithm which makes the training system much more efficient and reliable is
      described. RESULTS: Several necessary experiments are conducted to validate the
      vascular deformation scheme presented in this paper. From the results we can see
      that the position-based dynamic modeling method with volume conservation
      constraint can prevent the vascular deformation from the issue of penetration. In
      addition, the deformation calculation with spatial acceleration algorithm has
      enhanced the real-time performance significantly. CONCLUSION: The corresponding
      experimental results indicate that both the hybrid geometric blood vessel model
      and the hash table based spatial adaptive acceleration algorithm can enhance the
      performance of our surgery training system greatly without losing the deformation
      accuracy.

PMID- 27048291
TI  - Safety Evaluation of Sevoflurane as Anesthetic Agent in Mouse Model of Myocardial
      Ischemic Infarction.
AB  - The selection of anesthetics for patients with myocardial infarction is
      critically challenging. Sevoflurane is a volatile anesthetic gradually used in
      recent years. The intraoperative hemodynamic stability of sevoflurane was
      supported by several studies with some suggestions for its use for patients with
      cardiac events. The present study was undertaken to investigate the effect of
      sevoflurane on mice with myocardial infarction to evaluate the safety issue of
      this agent for possible application in patients with myocardial infarction. Mice
      of 7-12 weeks old were subjected to left anterior descending artery ligation to
      introduce acute myocardial infarction. The effect of sevoflurane on the
      hemodynamics was examined in comparison with that of currently available agent
      etomidate at low and moderate doses. The results showed that sevoflurane caused
      unstable hemodynamic changes in mice with myocardial infarction at both low and
      moderate inhaled concentrations relative to low and moderate doses of etomidate.
      In addition, the relative safety margin estimated from therapeutic index was
      decreased by 50 % when sevoflurane was used for mice with myocardial infarction
      relative to control mice, but only decreased by 20 % for etomidate. These
      analyses indicate that in comparison with currently available agent etomidate,
      sevoflurane should not be applied to patients with myocardial infarction or other
      cardiac events.

PMID- 27048292
TI  - Clinical Effectiveness and Safety of Analog Glargine in Type 1 Diabetes: A
      Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: The use of insulin analogs for the treatment of type 1 diabetes
      mellitus (T1DM) is widespread; however, the therapeutic benefits still require
      further evaluation given their higher costs. The objective of this study was to
      evaluate the effectiveness and safety of analog insulin glargine compared to
      recombinant DNA (rDNA) insulin in patients with T1DM in observational studies,
      building on previous reviews of randomized controlled trials comparing neutral
      protamine Hagedorn insulin and insulin glargine. METHODS: A systematic review
      with a meta-analysis was performed. The review included cohort studies and
      registries available on PubMed, LILACS, and the Cochrane Central Register of
      Controlled Trials (CENTRAL), as well as manual and gray literature searches. The
      meta-analysis was conducted in Review Manager 5.3 software. The primary outcomes
      were glycated hemoglobin (Hb1Ac), weight gain, and hypoglycemia. Methodological
      quality was assessed using the Newcastle-Ottawa scale. RESULTS: Out of 796
      publications, 11 studies were finally included. The meta-analysis favored insulin
      glargine in HbA1c outcomes (adult patients) and hypoglycemic episodes (P < 0.05),
      but without reaching glycemic control (Hb1Ac to approximately 7%). The
      methodological quality of the studies was moderate, noting that 45% of studies
      were funded by pharmaceutical companies. CONCLUSION: Given the high heterogeneity
      of the studies, the discrete value presented by the estimated effect on
      effectiveness and safety, potential conflicts of interest of the studies, and the
      appreciable higher cost of insulin glargine, there is still no support for
      recommending first-line therapy with analogs. The role of analogs in the
      treatment of T1DM could be better determined by further observational studies of
      good methodological quality to assess their long-term effectiveness and safety,
      as well as their cost-effectiveness.

PMID- 27048293
TI  - Genetic Diversity, Population Structure, and Linkage Disequilibrium in Bread
      Wheat (Triticum aestivum L.).
AB  - Bread wheat (Triticum aestivum L.) gene pool was analyzed with 117 microsatellite
      markers scattered throughout A, B, and D genomes. Ninety microsatellite markers
      were giving 1620 polymorphic alleles in 55 different bread wheat genotypes. These
      genotypes were found to be divided into three subgroups based on Bayesian model
      and Principal component analysis. The highest polymorphism information content
      value for the markers resides on A genome was estimated for wmc262 marker located
      on 4A chromosome with the polymorphism information content value of 0.960. The
      highest polymorphism information content value (0.954) among the markers known to
      be located on B genome was realized for wmc44 marker located on 1B chromosome.
      The highest polymorphism information content value for the markers specific to D
      genome was found in gwm174 marker located on 5D chromosome with the polymorphism
      information content value of 0.948. The presence of linkage disequilibrium
      between 81 pairwise SSR markers reside on the same chromosome was tested and very
      limited linkage disequilibrium was observed. The results confirmed that the most
      distant genotype pairs were as follows Ceyhan-99-Behoth 6, Gerek 79-Douma 40989,
      and Karahan-99-Douma 48114. 

PMID- 27048294
TI  - A Synthesis of Spiritual Intelligence Themes from Islamic and Western
      Philosophical Perspectives.
AB  - Spiritual intelligence is an emerging term that is widely discussed and accepted
      as one of the main components that addresses and solves many life problems.
      Nonetheless there is no specific study being done to synthesize the spiritual
      intelligence themes from Western and Islamic philosophical perspectives. This
      research aimed to identify common spiritual intelligence themes from these two
      perspectives and elucidated its contents by the view of two well-known Islamic
      scholars; al-Ghazali and Hasan Langgulung. Seven spiritual intelligence themes
      were identified through thematic analysis; meaning/purpose of life,
      consciousness, transcendence, spiritual resources, self-determination, reflection
      soul purification and spiritual coping with obstacles. These findings will be the
      groundwork for centered theory of spiritual intelligence themes that synthesize
      the Islamic and Western philosophical perspectives. It is hoped that this study
      will contribute significantly to the development of valid and reliable spiritual
      intelligence themes beyond the social and cultural boundaries. 

PMID- 27048295
TI  - Laparoscopic resection for T4 colon cancer: perioperative and long-term outcomes.
AB  - Laparoscopic resection has been considered a contraindication for T4 colorectal
      cancer. It is argued that it is a challenging and demanding procedure with high
      conversion rate, inadequate oncologic clearance and surgical outcomes. There are
      only a few data on short- and long-term operative results. This review aimed at
      assessing feasibility and operative and oncologic results of laparoscopic
      resection for T4 colorectal cancer. 

PMID- 27048296
TI  - Work-related discussions between French rheumatologists and their rheumatoid
      arthritis patients.
AB  - BACKGROUND: Rheumatoid arthritis (RA) causes significant impairment of physical
      function, and thus adversely affects patients' ability to work. AIMS: To document
      how often work limitations are discussed by rheumatologists and RA patients
      during consultations. METHODS: We conducted an observational study in a sample of
      French rheumatologists and in a parallel sample of patients recruited by
      pharmacists. We asked all rheumatologists in France practising in private
      practice or mixed practice (private practice and hospital) to participate in a
      telephone survey about their most recent consultation with an RA patient.
      Randomly selected pharmacists recruited RA patients to complete a questionnaire
      about their most recent consultation with their rheumatologist. We included
      patients aged 20-59, with a paid job or unemployed. We calculated the proportion
      of consultations including work-related discussions in both samples. RESULTS: Of
      the 1737 rheumatologists contacted, 153 (9%) described consultations with
      eligible patients. Of the 1200 pharmacists contacted, 39 (3%) recruited 81 RA
      patients. The proportion of consultations including work-related discussions was
      50% [95% confidence interval (CI) 42-58%] in the rheumatologist sample and 52%
      (95% CI 41-63%) in the patient sample. The most frequent subject of discussion
      (88%) was physical problems related to work in both samples. CONCLUSIONS: This is
      the first study to document the proportion of consultations where rheumatologists
      and their RA patients discuss work. Both specialists and patients reported that
      work was discussed in one in every two consultations.

PMID- 27048297
TI  - Systematic review: complementary therapies and employee well-being.
AB  - BACKGROUND: A variety of workplace-based interventions exist to reduce stress and
      increase productivity. However, the efficacy of these interventions is sometimes
      unclear. AIMS: To determine whether complementary therapies offered in the
      workplace improve employee well-being. METHODS: We performed a systematic
      literature review which involved an electronic search of articles published
      between January 2000 and July 2015 from the databases Cochrane Central Register
      of Controlled Trials, PsycINFO, MEDLINE, AMED, CINAHL Plus, EMBASE and PubMed. We
      also undertook a manual search of all applicable article reference lists to
      ensure that no relevant studies were missed. We only selected published, full
      length, English-language, peer-reviewed journal articles. Articles had to address
      the research objective using valid and reliable measures. We excluded articles
      concerning return to work or whose populations had been adversely affected by
      work resulting in the development of health issues. RESULTS: We included 10
      articles in the review from 131 identified. Mindfulness and meditation-based
      interventions were most effective in improving workplace health and work
      performance; the latter demonstrating some evidence of maintaining gains up to 3
      months later. The evidence for relaxation interventions was inconclusive.
      CONCLUSIONS: Mindfulness and meditation interventions may be helpful in improving
      both psychosocial workplace health and work performance, but long-term efficacy
      has yet to be fully determined.

PMID- 27048298
TI  - Train the trainer in dementia care. A program to foster communication skills in
      nursing home staff caring for dementia patients.
AB  - BACKGROUND: Improvement of communication skills in nursing home staff is key to
      provide better care for dementia patients and decrease occupational mental
      stress. OBJECTIVES: An innovative train-the-trainer program to improve and
      maintain professional caregivers' social competencies in nursing home dementia
      care is described. DESIGN AND METHODS: Over a period of 6 months, a group of 6
      senior staff members were qualified as program trainers (multiplicators) for the
      TANDEM training program, which qualified them to design, deliver, and evaluate
      training sessions that foster specific social competencies in dementia care. In a
      subsequent intervention study with 116 geriatric caregivers in 14 nursing homes,
      training was provided either by multiplicators (intervention group) or directly
      by project coworkers (control group). RESULTS: Participants in both groups
      improved their dementia-specific communication skills. In a follow-up survey, the
      intervention group also reported lasting reductions in mental stressors at work
      (p < 0.05) and occupational mental stress (p < 0.01) compared with the control
      group. CONCLUSIONS: The qualification of staff members in German nursing homes to
      be multiplicators for the TANDEM train-the-trainer program for dementia-specific
      communication skills has a beneficial influence on social competencies, mental
      stressors at work, and occupational mental stress of staff who care for dementia
      patients and may contribute to a sustainable implementation of dementia-specific
      social competencies.

PMID- 27048301
TI  - Experts call for younger men to be offered PSA test for prostate cancer.

PMID- 27048300
TI  - Inhibition of the classical pathway of the complement cascade prevents early
      dendritic and synaptic degeneration in glaucoma.
AB  - BACKGROUND: Glaucoma is a complex, multifactorial disease characterised by the
      loss of retinal ganglion cells and their axons leading to a decrease in visual
      function. The earliest events that damage retinal ganglion cells in glaucoma are
      currently unknown. Retinal ganglion cell death appears to be compartmentalised,
      with soma, dendrite and axon changes potentially occurring through different
      mechanisms. There is mounting evidence from other neurodegenerative diseases
      suggesting that neuronal dendrites undergo a prolonged period of atrophy,
      including the pruning of synapses, prior to cell loss. In addition, recent
      evidence has shown the role of the complement cascade in synaptic pruning in
      glaucoma and other diseases. RESULTS: Using a genetic (DBA/2J mouse) and an
      inducible (rat microbead) model of glaucoma we first demonstrate that there is
      loss of retinal ganglion cell synapses and dendrites at time points that precede
      axon or soma loss. We next determine the role of complement component 1 (C1) in
      early synaptic loss and dendritic atrophy during glaucoma. Using a genetic
      knockout of C1qa (D2.C1qa (-/-) mouse) or pharmacological inhibition of C1 (in
      the rat bead model) we show that inhibition of C1 is sufficient to preserve
      dendritic and synaptic architecture. CONCLUSIONS: This study further supports
      assessing the potential for complement-modulating therapeutics for the prevention
      of retinal ganglion cell degeneration in glaucoma.

PMID- 27048302
TI  - A comparison of cranial fluctuating asymmetry between the two sexes in a Joseon
      Dynasty population of Korea.
AB  - SUMMARY: Cranial fluctuating asymmetry (FA) has been used to examine
      developmental stress levels in various populations. In bioarchaeological studies,
      developmental stress can be an important factor for inferring standard of living
      in a population. However, the crania of a Joseon Dynasty population have only
      been studied in terms of its morphological characteristics. In this regard, the
      cranial FA of the two sexes from a Joseon Dynasty population of Korea were
      compared here for examining their aspects of living conditions in relation to
      developmental stress and socio-cultural factors. In this study, 77 individuals
      (39 males and 38 females) who belong to the 15th to the early-20th centuries from
      Seoul and Gyeonggi province in Korea were investigated. Nineteen three
      dimensional landmarks on the vault and basicranium were collected using
      MicroScribe G2X. The coordinate data were aligned into a common coordinate plane
      by Procrustes least-squares superimposition. Procrustes ANOVA was adopted to
      evaluate FA at a population level. The FA of males and females were compared with
      t-test using SPSS 18. There was statistically insignificant difference in FA
      between the two sexes in the Joseon Dynasty population. The result was
      interpreted to reflect both relatively high developmental stress and sex-related
      discrimination in the population. It was postulated that relatively high
      developmental stress could increase difference in FA between the two sexes in the
      prenatal term compared to the postnatal term because sex-related discrimination
      cannot be practiced before birth and males have lower stress resistance than
      females. Then, the difference between the two sexes in the cranial FA could be
      decreased during postnatal development related to sex-related discrimination,
      resulting in insignificant FA difference of the two sexes in spite of high
      developmental stress of the Joseon Dynasty population. The results will be useful
      for comparing and reconstructing living conditions of ancient Korean populations.

PMID- 27048303
TI  - Inhibition of the Mechanistic Target of Rapamycin (mTOR)-Rapamycin and Beyond.
AB  - Rapamycin is a Food and Drug Administration (FDA)-approved immunosuppressant and
      anticancer agent discovered in the soil of Easter Island in the early 1970s.
      Rapamycin is a potent and selective inhibitor of the mechanistic target of
      rapamycin (mTOR) protein kinase, which acts as a central integrator of nutrient
      signaling pathways. During the last decade, genetic and pharmaceutical inhibition
      of mTOR pathway signaling has been found to promote longevity in yeast, worms,
      flies, and mice. In this article, we will discuss the molecular biology
      underlying the effects of rapamycin and its physiological effects, evidence for
      rapamycin as an antiaging compound, mechanisms by which rapamycin may extend life
      span, and the potential limitations of rapamycin as an antiaging molecule.
      Finally, we will discuss possible strategies that may allow us to inhibit mTOR
      signaling safely while minimizing side effects, and reap the health, social, and
      economic benefits from slowing the aging process.

PMID- 27048304
TI  - p53 in the DNA-Damage-Repair Process.
AB  - The cells in the human body are continuously challenged by a variety of genotoxic
      attacks. Erroneous repair of the DNA can lead to mutations and chromosomal
      aberrations that can alter the functions of tumor suppressor genes or oncogenes,
      thus causing cancer development. As a central tumor suppressor, p53 guards the
      genome by orchestrating a variety of DNA-damage-response (DDR) mechanisms.
      Already early in metazoan evolution, p53 started controlling the apoptotic demise
      of genomically compromised cells. p53 plays a prominent role as a facilitator of
      DNA repair by halting the cell cycle to allow time for the repair machineries to
      restore genome stability. In addition, p53 took on diverse roles to also directly
      impact the activity of various DNA-repair systems. It thus appears as if p53 is
      multitasking in providing protection from cancer development by maintaining
      genome stability.

PMID- 27048305
TI  - Texas hospitals with higher health information technology expenditures have
      higher revenue: A longitudinal data analysis using a generalized estimating
      equation model.
AB  - BACKGROUND: The benefits of health information technology (IT) adoption have been
      reported in the literature, but whether health IT investment increases revenue
      generation remains an important research question. METHODS: Texas hospital data
      obtained from the American Hospital Association (AHA) for 2007-2010 were used to
      investigate the association of health IT expenses and hospital revenue. The
      generalized estimation equation (GEE) with an independent error component was
      used to model the data controlling for cluster error within hospitals. RESULTS:
      We found that health IT expenses were significantly and positively associated
      with hospital revenue. Our model predicted that a 100% increase in health IT
      expenditure would result in an 8% increase in total revenue. The effect of health
      IT was more associated with gross outpatient revenue than gross inpatient
      revenue. CONCLUSION: Increased health IT expenses were associated with greater
      hospital revenue. Future research needs to confirm our findings with a national
      sample of hospitals.

PMID- 27048306
TI  - Comparative effectiveness of coronary CT angiography vs stress cardiac imaging in
      patients following hospital admission for chest pain work-up: The Prospective
      First Evaluation in Chest Pain (PERFECT) Trial.
AB  - BACKGROUND: Because the frequency of cardiac event rates is low among chest pain
      patients following either performance of coronary CT angiography (CCTA) or stress
      testing, there is a need to better assess how these tests influence the central
      management decisions that follow from cardiac testing. The present study was
      performed to assess the relative impact of CCTA vs stress testing on medical
      therapies and downstream resource utilization among patients admitted for the
      work-up of chest pain. METHODS: The admitted patients were randomized in a 1:1
      ratio to either cardiac imaging stress test or CCTA. Primary outcomes were time
      to discharge, change in medication usage, and frequency of downstream testing,
      cardiac interventions, and cardiovascular re-hospitalizations. We randomized 411
      patients, 205 to stress testing, and 206 to CCTA. RESULTS: There were no
      differences in time to discharge or initiation of new cardiac medications at
      discharge. At 1 year follow-up, there was no difference in the number of patients
      who underwent cardiovascular downstream tests in the CCTA vs stress test patients
      (21% vs 15%, P = .1) or cardiovascular hospitalizations (14% vs 16%, P = .5).
      However, there was a higher frequency of invasive angiography in the CCTA group
      (11% vs 2%, P = .001) and percutaneous coronary interventions (6% vs 0%, P <
      .001). CONCLUSIONS: Randomization of hospitalized patients admitted for chest
      pain work-up to either CCTA or to stress testing resulted in similar discharge
      times, change in medical therapies at discharge, frequency of downstream
      noninvasive testing, and repeat hospitalizations. However, a higher frequency of
      invasive coronary angiography and revascularization procedures were performed in
      the CCTA arm. (ClinicalTrials.gov number, NCT01604655.).

PMID- 27048308
TI  - The right timing for post-ischemic stunning.

PMID- 27048309
TI  - A useful annual review of cognition in relapsing MS is beyond most neurologists -
      Commentary.

PMID- 27048307
TI  - Sex affects myocardial blood flow and fatty acid substrate metabolism in humans
      with nonischemic heart failure.
AB  - BACKGROUND: In animal models of heart failure (HF), myocardial metabolism shifts
      from high-energy fatty acid (FA) metabolism toward glucose. However, FA (vs
      glucose) metabolism generates more ATP/mole; thus, FA metabolism may be
      especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and
      substrate metabolism in normal humans. Whether sex affects MBF and metabolism in
      patients with HF is unknown. METHODS AND RESULTS: We studied 19 well-matched men
      and women with nonischemic HF (EF <= 35%). MBF and myocardial substrate
      metabolism were quantified using positron emission tomography. Women had higher
      MBF (mL/g/minute), FA uptake (mL/g/minute), and FA utilization (nmol/g/minute) (P
      < 0.005, P < 0.005, P < 0.05, respectively) and trended toward having higher FA
      oxidation than men (P = 0.09). These findings were independent of age, obesity,
      and insulin resistance. There were no sex-related differences in fasting
      myocardial glucose uptake or metabolism. Higher MBF was related to improved event
      free survival (HR 0.31, P = 0.02). CONCLUSIONS: In nonischemic HF, women have
      higher MBF and FA uptake and metabolism than men, irrespective of age, obesity,
      or insulin resistance. Moreover, higher MBF portends a better prognosis. These
      sex-related differences should be taken into account in the development and
      targeting of novel agents aimed at modulating MBF and metabolism in HF.

PMID- 27048310
TI  - A useful annual review of cognition in relapsing MS is beyond most neurologists -
      YES.

PMID- 27048311
TI  - A useful annual review of cognition in relapsing MS is beyond most neurologists -
      NO.

PMID- 27048313
TI  - Endovascular treatment of frontopolar artery aneurysm.
AB  - Traumatic intracranial aneurysms are rare and usually present with subarachnoid
      hemorrhage, intracranial hemorrhage, subdural hematoma, or intraventricular
      hemorrhage. These are usually not true aneurysms; hence treatment of these cases
      poses a therapeutic challenge. In this case report, we describe a young Asian
      male who presented with a ruptured pseudoaneurysm of the distal branch of the
      anterior cerebral artery. It was treated successfully with endovascular
      embolization. To our knowledge, there are few reports of this entity in the
      literature. 

PMID- 27048312
TI  - The use of onabotulinum toxin A (Botox((r))) in the treatment of chronic migraine
      at the Parma Headache Centre: a prospective observational study.
AB  - Chronic migraine is a debilitating headache, whose treatment is often complicated
      by the concomitant overuse of symptomatic medication and by the poor efficacy of
      standard prophylactic treatments. The PREEMPT studies have demonstrated the
      efficacy and tolerability of onabotulinum toxin A (Botox((r))) in the treatment
      of this headache type. Data about its use in clinical practice are still scarce.
      Our study evaluated all subjects with chronic migraine who were treated with
      onabotulinum toxin A between February 2014 and November 2015 at the Parma
      Headache Centre. Botox was injected according to the PREEMPT paradigm every 3
      months. The data about variations in the number of headache days and in
      symptomatic medication intake before and after the Botox injections were
      collected from the patients' headache diaries. The study also evaluated
      tolerability to treatment, disability, and depressive symptoms. Of the 52 treated
      subjects, 14 received Botox treatment for at least 9 months and showed a
      significant decrease in the median number of headache days (from 19 to 14.5, p =
      0.011) and in the median number of days of symptomatic medications intake and
      symptomatic drugs. Overall, the treatment was well tolerated. The average MIDAS
      and BDI-II scores after 9 months were reduced, though not significantly. The
      treatment with Botox proved effective and well tolerated in our clinical
      practice. Further studies on larger patient samples will help shed light on the
      persistence of the drug's effect at long term and identify the predictive factors
      of response to treatment. 

PMID- 27048314
TI  - EUROarray human papillomavirus (HPV) assay is highly concordant with other
      commercial assays for detection of high-risk HPV genotypes in women with high
      grade cervical abnormalities.
AB  - The purpose of this study was to evaluate the performance of the EUROIMMUN
      EUROArray HPV genotyping assay against the Roche Cobas 4800, Roche HPV Amplicor,
      Roche Linear Array and Qiagen Hybrid Capture 2 assays in the detection of high
      risk HPV (HR-HPV) from liquid based cervical cytology samples collected from
      women undergoing follow-up for abnormal cervical cytology results. Cervical
      specimens from 404 women undergoing management of high-grade cytological
      abnormality were evaluated by EUROarray HPV for detection of HR-HPV genotypes and
      prediction of histologically-confirmed cervical intraepithelial neoplasia grade 2
      or higher (>=CIN2). The results were compared to Hybrid Capture 2, Cobas 4800
      HPV, Amplicor and Linear Array HPV. Positivity for 14 HR-HPV types was 80.0 % for
      EUROarray (95 % CI; 75.7-83.8 %). Agreement (kappa, 95 % CI) between the
      EUROarray and other HPV tests for detection of HR-HPV was good to very good
      [Hybrid Capture kappa = 0.62 (0.54-0.71); Cobas kappa = 0.81 (0.74-0.88);
      Amplicor kappa = 0.68 (0.60-0.77); Linear Array kappa = 0.77 (0.70-0.85)]. For
      detection of HR-HPV, agreement with EUROarray was 87.90 % (Hybrid Capture), 93.58
      % (Cobas), 92.84 % (Amplicor) and 92.59 % (Linear Array). Detection of HR-HPV was
      not significantly different between EUROarray and any other test (p < 0.001).
      EUROarray was concordant with other assays evaluated for detection of high-risk
      HPV and showed sensitivity and specificity for detection of >= CIN2 of 86 % and
      71 %, respectively. 

PMID- 27048315
TI  - Procedural sedation and its place in paediatric emergency medicine.

PMID- 27048316
TI  - Tranexamic acid: there's new life in the old drug.

PMID- 27048317
TI  - Purpura on the truncus and extremities.

PMID- 27048319
TI  - The utility of resilience as a conceptual framework for understanding and
      measuring LGBTQ health.
AB  - BACKGROUND: Historically, lesbian, gay, bisexual, transgender and queer (LGBTQ)
      health research has focused heavily on the risks for poor health outcomes,
      obscuring the ways in which LGBTQ populations maintain and improve their health
      across the life course. In this paper we argue that informing culturally
      competent health policy and systems requires shifting the LGBTQ health research
      evidence base away from deficit-focused approaches toward strengths-based
      approaches to understanding and measuring LGBTQ health. METHODS: We recently
      conducted a scoping review with the aim of exploring strengths-based approaches
      to LGBTQ health research. Our team found that the concept of resilience emerged
      as a key conceptual framework. This paper discusses a subset of our scoping
      review findings on the utility of resilience as a conceptual framework in
      understanding and measuring LGBTQ health. RESULTS: The findings of our scoping
      review suggest that the ways in which resilience is defined and measured in
      relation to LGBTQ populations remains contested. Given that LGBTQ populations
      have unique lived experiences of adversity and discrimination, and may also have
      unique factors that contribute to their resilience, the utility of
      heteronormative and cis-normative models of resilience is questionable. Our
      findings suggest that there is a need to consider further exploration and
      development of LGBTQ-specific models and measures of resilience that take into
      account structural, social, and individual determinants of health and incorporate
      an intersectional lens. CONCLUSIONS: While we fully acknowledge that the
      resilience of LGBTQ populations is central to advancing LGBTQ health, there
      remains much work to be done before the concept of resilience can be truly useful
      in measuring LGBTQ health.

PMID- 27048318
TI  - The role of neoantigens in response to immune checkpoint blockade.
AB  - Immune checkpoint blockade has demonstrated substantial promise for the treatment
      of several advanced malignancies. These agents activate the immune system to
      attack tumor cells. For example, agents targeting CTLA4 and programmed cell death
      1 (PD-1) have resulted in impressive response rates and, in some cases, durable
      remissions. Neoantigens are mutations that encode immunologically active proteins
      that can cause the immune system to recognize the affected cell as foreign.
      Recent data have made it clear that these mutations are, in large part, the
      functional targets of immune checkpoint blockade. This review summarizes the key
      discoveries leading up to this important conclusion and discusses possible
      applications of neoantigens in cancer therapy.

PMID- 27048320
TI  - Tapentadol PR for Pain Syndromes in Real Life Patients with Hematological
      Malignancy.
AB  - BACKGROUND: More than 50% of oncohematological patients suffer from pain
      syndrome, mostly originating from the bone, which often include nociceptive and
      neuropathic complaints. Tapentadol, a recently available treatment option for
      cancer pain, exerts a dual analgesic mechanisms (opioid and noradrenergic),
      allowing for a high clinical efficacy as well as for a reduction in adverse
      events compared to traditional opioids. AIM: To explore the safety and efficacy
      of tapentadol as a suitable agent for the pain management in the setting of
      oncohematology. METHODS: Our observational study included 36 patients with basal
      pain intensity (NRS) ranging from 5 to 10. Tapentadol prolonged release (PR) was
      given at the initial dose of 50 mg BID and careful titrated according to the
      achieved pain control. RESULTS: Tapentadol PR was given at the dosages ranging
      from 200 and 260 mg/day after a careful titration, allowed for a clinically (-7
      points NRS) remarkable reduction of pain intensity without any significant side
      effects. CONCLUSION: In oncohematological patients on pain, tapentadol PR was
      effective and well tolerated, so representing a suitable treatment option in this
      difficult setting.

PMID- 27048321
TI  - NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells.
AB  - The proteoglycan neuron-glial antigen 2 (NG2) is expressed by oligodendrocyte
      progenitors, pericytes, and some cancerous cells where it is implicated in tumor
      development. We examined mice with NG2-driven pRb inactivation. Unexpectedly, NG2
      Cre:pRb(flox/flox) mice developed pituitary tumors with high penetrance.
      Adenohypophysial neoplasms developed initially as multifocal lesions; by 1 year,
      large tumors showed brain invasion. Immunohistochemistry identified these as Pit1
      lineage neoplasms, with variable immunoreactivity for growth hormone, prolactin,
      thyrotropin, and alpha-subunit of glycoprotein hormones. Other than modest
      hyperprolactinemia, circulating hormone levels were not elevated. To determine
      the role of NG2 in the pituitary, we investigated NG2 expression.
      Immunoreactivity was identified in anterior and posterior lobes but not in the
      intermediate lobe of the mouse pituitary; in the adenohypophysis,
      folliculostellate cells had the strongest NG2 immunoreactivity but showed no
      proliferation in response to Rb inactivation. Pit1-positive adenohypophysial
      cells were positive for NG2, but corticotroph and gonadotroph cells were
      negative. RT-PCR revealed NG2 expression in normal human pituitary and human
      pituitary tumors; immunohistochemistry localized NG2 in nontumorous human
      adenohypophysis with strongest positivity in folliculostellate cells, and in
      tumors of all types except corticotrophs. Functional studies in GH4
      mammosomatotrophs showed that NG2 increases prolactin (PRL), reduces growth
      hormone (GH) expression, and enhances cell adhesion without influencing
      proliferation. In conclusion, NG2-driven pRb inactivation results in pituitary
      tumors that mimic endocrinologically inactive Pit1-lineage human pituitary
      tumors. This model identifies a role for NG2 in pituitary cell-type-specific
      functions and unmasks a protective role from Rb inactivation in folliculostellate
      cells; it can be used for further research, including preclinical testing of
      novel therapies.

PMID- 27048322
TI  - Phenotypic and genotypic characteristics of carbapenem-resistant
      Enterobacteriaceae in a tertiary-level reference hospital in Turkey.
AB  - BACKGROUND: Enterobacteriaceae are among the most common pathogens that are
      responsible for serious community-acquired, hospital-acquired, and health-care
      associated infections. The emergence and spread of carbapenem-resistant
      Enterobacteriaceae (CRE) have become an increasing concern for healthcare
      services worldwide. Infections caused by these bacteria have been associated with
      significant morbidity and mortality and treatment options have been limited. The
      rapid and accurate detection of carbapenem resistance in these bacteria is
      important for infection control. The aim of this study was to investigate the
      phenotypic and genotypic features of CRE strains isolated in a tertiary-level
      reference hospital in Turkey. METHODS: A total of 181 CRE strains were included
      in the study. Antimicrobial susceptibility rates were tested using Vitek 2
      system. Modified Hodge test (MHT) was performed using meropenem and ertapenem
      discs. Metallo-beta-lactamase antimicrobial gradient test (E-test MBL strips)
      were used for evaluation of metallo-beta-lactamase production. A multiplex PCR
      was used for detection of carbapenems resistance genes (IMP, VIM, KPC, NDM-1 and
      OXA-48). RESULTS: The OXA-48 gene was detected in 86 strains, NDM-1 gene in six
      strains, VIM gene in one strain. IMP and KPC genes were not identified. Three
      strains produced both OXA-48 and NDM-1 and one strain produced both OXA-48 and
      VIM. In two patients more than one genus of OXA-48 positive CREs was isolated.
      Ninety-two of the isolates were multidrug-resistant. One hundred and ten isolates
      were MHT with meropenem (MEM-MHT) positive and 109 isolates were MHT with
      ertapenem (ERT-MHT) positive. Nine of the isolates were positive with E-test MBL
      strips. The sensitivity of MEM-MHT and ERT-MHT for detection of OXA-48 was 70.9
      and 70.6 %, respectively. MEM-MHT was found highly discriminative for OXA-48
      Escherichia coli (p < 0.001). The sensitivity of E-test MBL for NDM-1 was 66.7 %.
      A statistically significant correlation was observed between OXA-48 gene and MHT
      positivity and between NDM-1, VIM gene and E-test MBL positivity (p < 0.001).
      CONCLUSIONS: OXA-48 gene is spreading rapidly to many different species of
      Enterobacteriaceae in the hospital environment. While OXA-48 is still the most
      common source of carbapenem resistance in Enterobacteriaceae in our country, NDM
      1 is increasingly being isolated from patients without a history of foreign
      contact.

PMID- 27048323
TI  - The importance of GC-MS date processing and analysis strategies suitable for
      plant and environmental metabolomics : with references to Changes in the
      abundance of sugars and sugar-like compounds in tall fescue (Festuca arundinacea)
      due to growth in naphthalene-treated sand.

PMID- 27048324
TI  - Submerged macrophytes shape the abundance and diversity of bacterial denitrifiers
      in bacterioplankton and epiphyton in the Shallow Fresh Lake Taihu, China.
AB  - nirK and nirS genes are important functional genes involved in the
      denitrification pathway. Recent studies about these two denitrifying genes are
      focusing on sediment and wastewater microbe. In this study, we conducted a
      comparative analysis of the abundance and diversity of denitrifiers in the
      epiphyton of submerged macrophytes Potamogeton malaianus and Ceratophyllum
      demersum as well as in bacterioplankton in the shallow fresh lake Taihu, China.
      Results showed that nirK and nirS genes had significant different niches in
      epiphyton and bacterioplankton. Bacterioplankton showed greater abundance of nirK
      gene in terms of copy numbers and lower abundance of nirS gene. Significant
      difference in the abundance of nirK and nirS genes also existed between the
      epiphyton from different submerged macrophytes. Similar community diversity yet
      different community abundance was observed between epiphytic bacteria and
      bacterioplankton. No apparent seasonal variation was found either in epiphytic
      bacteria or bacterioplankton; however, environmental parameters seemed to have
      direct relevancy with nirK and nirS genes. Our study suggested that submerged
      macrophytes have greater influence than seasonal parameters in shaping the
      presence and abundance of bacterial denitrifiers. Further investigation needs to
      focus on the potential contact and relative contribution between denitrifiers and
      environmental factors. 

PMID- 27048325
TI  - The potential for constructed wetlands to treat alkaline bauxite residue
      leachate: laboratory investigations.
AB  - High alkalinity (pH > 12) of bauxite residue leachates presents challenges for
      the long-term storage and managements of the residue. Whilst the use of
      constructed wetlands is gaining in interest for its use in the treatment of
      alkaline waters, thus far, there is limited evidence of its suitability for
      treating NaOH dominated bauxite residue leachate. A series of batch trials were
      conducted to investigate the potential for constructed wetland conferred
      mechanisms (dilution water quality, contact with CO2, and substrate type) for
      treating NaOH solutions to levels permissible for discharge (p < 9). Results
      demonstrate that significant reductions in solution pH can be achieved depending
      on the diluting water quality. Levels achieved may not always be suitable for
      direct discharge (i.e. pH <= 9), but further reductions occur with carbonation
      and soil contact. The extent of pH decrease and the timeframe required are
      influenced by soil quality, with greater efficiency observed in soils with higher
      organic matter content. Decrease in solution pH to discharge permit values are
      possible through a combination of the mechanisms occurring in a constructed
      wetland. Formation of a calcite precipitate was observed in some treatments and
      further characterisation by XRD and XPS suggested surface coating with Na2CO3. It
      is therefore suggested that, under suitable conditions, constructed wetland
      technology can reduce leachate pH to <9 through mechanisms supporting the
      precipitation of sodium carbonate from solution. Further trials should
      investigate the activity under biological conditions representative of an
      operating constructed wetland. 

PMID- 27048326
TI  - Mediterranean aerosol typing by integrating three-wavelength lidar and sun
      photometer measurements.
AB  - Backscatter lidar measurements at 355, 532, and 1064 nm combined with aerosol
      optical thicknesses (AOTs) from sun photometer measurements collocated in space
      and time were used to retrieve the vertical profiles of intensive and extensive
      aerosol parameters. Then, the vertical profiles of the Angstrom coefficients for
      different wavelength pairs (A(lambda1, lambda2, z)), the color ratio (CR(z)), the
      fine mode fraction (eta(z)) at 532 nm, and the fine modal radius (R f (z)), which
      represent aerosol characteristic properties independent from the aerosol load,
      were used for typing the aerosol over the Central Mediterranean. The ability of
      the Angstrom coefficients to identify the main aerosol types affecting the
      Central Mediterranean with the support of the backward trajectory analysis was
      first demonstrated. Three main aerosol types, which were designed as continental
      polluted (CP), marine-polluted (MP), and desert-polluted (DP), were identified.
      We found that both the variability range and the vertical profile structure of
      the tested aerosol intensive parameters varied with the aerosol type. The
      variability range and the altitude dependence of the aerosol extinction
      coefficients at 355, 532, and 1064 nm, respectively, also varied with the
      identified aerosol types even if they are extensive aerosol parameters. DP, MP,
      and CP aerosols were characterized by the A(532, 1064 nm) mean values +/- 1
      standard deviation equal to 0.5 +/- 0.2, 1.1 +/- 0.2, 1.6 +/- 0.2, respectively.
      eta(%) mean values +/- 1SD were equal to 50 +/- 10, 73 +/- 7, and 86 +/- 6 for
      DP, MP, and CP aerosols, respectively. The R f and CR mean values +/- 1SD were
      equal to 0.16 +/- 0.05 MUm and 1.3 +/- 0.3, respectively, for DP aerosols; to
      0.12 +/- 0.03 MUm and 1.8 +/- 0.4, respectively, for MP aerosols; and to 0.11 +/-
      0.02 MUm and 1.7 +/- 0.4, respectively, for CP aerosols. CP and DP aerosols were
      on average responsible for greater AOT and LR values, but the LR and AOT
      dependence on wavelength was stronger for CP than for DP aerosols. The plots of
      the lidar ratio values at 355 nm versus the mean columnar values of the 532-1064
      nm Angstrom coefficient (A c), the fine mode radius, the fine mode fraction at
      532 nm (eta c), and the color ratio, respectively, furthermore revealed the
      greater ability of the A c and eta c values to characterize different aerosol
      types. 

PMID- 27048327
TI  - Impact of extreme oxygen consumption by pollutants on macroinvertebrate
      assemblages in plain rivers of the Ziya River Basin, north China.
AB  - The aim of the study was to estimate the impact of oxygen depletion on
      macroinvertebrate community structure in benthic space. Macroinvertebrate
      assemblages and potential of dissolved oxygen (DO) consumption were investigated
      simultaneously in the plain rivers of the Ziya River Basin. The degree of DO
      depletion was represented by sediment oxygen demand (SOD) and DO, chemical oxygen
      demand (CODCr), and ammonia nitrogen (NH4 (+)-N) in the overlying water. The
      results showed an all-around hypoxia environment formed, and the values of DO,
      SOD, CODCr, and NH4 (+)-N were separately 0.11-4.03 mg L(-1), 0.41-2.60 g m(-2)
      day(-1), 27.50-410.00 mg L(-1), and 1.79-101.41 mg L(-1). There was an abnormal
      macroinvertebrate assemblage, and only 3 classes, Insecta, Gastropoda, and
      Oligochaeta, were found, which included 9 orders, 30 families, and 54 genera. The
      biodiversity was at a low level, and Shannon-Wiener index was 0.00-1.72. SOD, and
      NH4 (+)-N had major impact on the macroinvertebrate community, and the former had
      negative effect on most taxa, for instance, Nais, Branchiura, Paraleptophlebia,
      etc., which were sensitive or had a moderate-high tolerance to pollution. NH4 (+)
      N had both positive and negative impacts on benthic animals, for instance,
      Dicrotendipes, Gomphus, Cricotopus, etc., for the former, and Procladius,
      Limnodrilus, Hippeutis, etc., for the latter. They all had a moderate-high
      tolerance to pollution. It is significant to improve DO condition and
      macroinvertebrate diversity in river harnessing and management. 

PMID- 27048328
TI  - Wintertime chemical compositions of coarse and fine fractions of particulate
      matter in Bolu, Turkey.
AB  - Coarse (particulate matter (PM)2.5-10) and fine (PM2.5) fraction of PM samples
      were collected between December 2014 and February 2015 at an urban sampling site
      located at the Bolu plain, of the western Black Sea region of Turkey. The
      collected samples were analyzed in terms of metals (Al, As, Ba, Ca, Cu, Fe, K,
      Mg, Mn, Na, Pb, S, Si, Ti, V, and Zn); elemental carbon (EC); and organic carbon
      (OC). Elevated concentrations measured in this wintertime study were ~7.8
      MUg/m(3) in sum of PM2.5-10 and PM2.5 for SO4 (2-) and ~59.9 MUg/m(3) in PM2.5
      for OC. The contributions of primary and secondary OC (POC and SOC, respectively)
      to total OC mass were 60 and 40 %, respectively, while contribution of SOC to OC
      increased by up to 74 % in stable atmospheric conditions. The significantly high
      OC/EC ratio (~10.1) found in this study relative to other wintertime studies was
      attributed to increased emissions from residential heating and lower mixing
      height observed during the study. Two and three factors were resolved by factor
      analysis for PM2.5-10 and PM2.5, respectively. Two Saharan dust episodes were
      observed on 31 January and 1 February, during which crustal PM components such as
      Mg, Si, and Al increased as much as three times their background concentrations. 

PMID- 27048330
TI  - Free the NHS from the shackles of incompetent central control.

PMID- 27048329
TI  - Contribution of inorganic arsenic sources to population exposure risk on a
      regional scale.
AB  - Chronic exposure to inorganic arsenic (iAs) in the human population is associated
      with various internal cancers and other adverse outcomes. The purpose of this
      study was to estimate a population-scale exposure risk attributable to iAs
      consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK)
      model and biomonitoring data of iAs in urine. The urinary As concentrations were
      obtained from a total of 1,043 subjects living in an industrial area of Taiwan.
      The results showed that the study subjects had an iAs exposure risk of 27 % (the
      daily iAs intake for 27 % study subjects exceeded the WHO-recommended value, 2.1
      MUg iAs day(-1) kg(-1) body weight). Moreover, drinking water and cooked rice
      contributed to the iAs exposure risk by 10 and 41 %, respectively. The predicted
      risks in the current study were 4.82, 27.21, 34.69, and 64.17 %, respectively,
      among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh
      reported in the literature. In conclusion, we developed a population-scale-based
      risk model that covered the broad range of iAS exposure by integrating stochastic
      PBPK modeling and reverse dosimetry to generate probabilistic distribution of As
      intake corresponding to urinary As measured from the cohort study. The model can
      also be updated as new urinary As information becomes available. 

PMID- 27048331
TI  - Posttraumatic myositis ossificans of the hand : A locally aggressive malignancy
      mimicking tumor.
AB  - Posttraumatic myositis ossificans (PTMO) is the most common form of myositis
      ossificans, but it rarely affects the hand. Due to the aggressive behavior of
      this unusual tumor, it is commonly misdiagnosed as malignancy or local infection.
      This report describes a case of PTMO of the hand in a 25-year-old women, and
      reviews the clinical, radiologic, and histologic characteristics. By
      understanding the disease characteristics and maturation process, physicians can
      avoid a misdiagnosis that may lead to functional impairment or improper
      treatment. 

PMID- 27048332
TI  - Learning defects in Drosophila growth restricted chico mutants are caused by
      attenuated adenylyl cyclase activity.
AB  - BACKGROUND: Reduced insulin/insulin-like growth factor signaling (IIS) is a major
      cause of symmetrical intrauterine growth retardation (IUGR), an impairment in
      cell proliferation during prenatal development that results in global growth
      defects and mental retardation. In Drosophila, chico encodes the only insulin
      receptor substrate. Similar to other animal models of IUGR, chico mutants have
      defects in global growth and associative learning. However, the physiological and
      molecular bases of learning defects caused by chico mutations, and by symmetrical
      IUGR, are not clear. RESULTS: In this study, we found that chico mutations impair
      memory-associated synaptic plasticity in the mushroom bodies (MBs), neural
      centers for olfactory learning. Mutations in chico reduce expression of the
      rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the
      MBs. Expressing a rut (+) transgene in the MBs restores memory-associated
      plasticity and olfactory associative learning in chico mutants, without affecting
      growth. Thus chico mutations disrupt olfactory learning, at least in part, by
      reducing cAMP signaling in the MBs. CONCLUSIONS: Our results suggest that some
      cognitive defects associated with reduced IIS may occur, independently of
      developmental defects, from acute reductions in cAMP signaling.

PMID- 27048334
TI  - PulmoCor: national registry for pulmonary hypertension.

PMID- 27048333
TI  - The effect of oxytocin on attention to angry and happy faces in chronic
      depression.
AB  - BACKGROUND: Chronic depression is characterized by a high degree of early life
      trauma, psychosocial impairment, and deficits in social cognition. Undisturbed
      recognition and processing of facial emotions are basic prerequisites for smooth
      social interactions. Intranasal application of the neuropeptide oxytocin has been
      reported to enhance emotion recognition in neuropsychiatric disorders and healthy
      individuals. We therefore investigated whether oxytocin modulates attention to
      emotional faces in patients with chronic depression. METHODS: In this double
      blind, randomized, controlled study, 43 patients received a single dose of
      oxytocin or placebo nasal spray and were tested while fulfilling a facial dot
      probe task. We assessed reaction times to neutral probes presented at the
      location of one of two faces depicting happy, angry, or neutral expressions as a
      prime. RESULTS: When comparing reaction times to the congruent (prime and probe
      at the same location) with incongruent presentation of facial emotions, neither
      the placebo nor oxytocin group showed an attentional preference for emotional
      facial expressions in terms of a threat bias. However, oxytocin treatment did
      reveal two specific effects: it generally reduced the allocation of attention
      towards angry facial expressions, and it increased sustained attention towards
      happy faces, specifically under conditions of heightened awareness, i.e. trials
      with longer primes. CONCLUSIONS: We investigated a heterogeneous group of
      medicated male and female patients. We conclude that oxytocin does modulate basic
      factors of facial emotion processing in chronic depression. Our findings
      encourage further investigations assessing the therapeutic potential of oxytocin
      in chronic depression. TRIAL REGISTRATION: EUDRA-CT 2010-020956-69 . Date
      registered: 23 February 2011.

PMID- 27048335
TI  - Abscisic Acid: A Phytohormone and Mammalian Cytokine as Novel Pharmacon with
      Potential for Future Development into Clinical Applications.
AB  - The isoprenoid stress-associated phytohormone abscisic acid (ABA) has recently
      been recognized to possess multifaceted biological functions in mammals and to
      exert potent curative effects in a number of clinically relevant human diseases.
      Studies with human specimens have unequivocally shown that ABA retains its stress
      related functional attributes, previously identified in plants, which contribute
      to enhanced inflammatory defense mechanisms in mammals. Besides, studies
      performed in animal models revealed prominent anti-inflammatory properties of ABA
      as indicated by a marked reduction of immune cell infiltrates at the sites of
      inflammation. Thus, ABA treatment ultimately leads to the profound improvement of
      both non-communicable and communicable diseases which are associated with an
      overall alleviated course of inflammation. In addition to its action on the
      mammalian immune system, ABA was also shown to exert diverse physiological
      functions on non-immune components. One of the most remarkable features of ABA is
      to stimulate and expand mesenchymal stem cells, which may open a new avenue for
      its potential use in the field of regenerative medicine. Furthermore, ABA has
      been reported to play an important role in the maintenance of glycemic control.
      In this review, we summarize current understanding of the significance of ABA in
      the mammalian system, its prophylactic and therapeutic effects in various disease
      settings and the future directions for the development of ABA as novel drug
      candidate for the improved treatment of inflammatory and infectious human
      diseases. 

PMID- 27048336
TI  - Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells.
AB  - Aberrant expression and activation of receptor tyrosine kinases (RTK) is a
      frequent feature of tumor cells that may underlie tumor aggressiveness. Among
      RTK, Axl, a member of the Tyro3-Axl-Mer family, represents a potential
      therapeutic target in different tumor types given its over-expression which leads
      to activation of oncogenic signaling promoting cell proliferation and survival,
      as well as migration and invasion. Axl can promote aggressiveness of various cell
      types through PI3K/Akt and/or MAPK/ERK, and its expression can be
      transcriptionally regulated by multiple factors. Deregulated Axl expression and
      activation have been shown to be implicated in reduced sensitivity of tumor cells
      to target-specific and conventional antitumor agents, but the precise mechanism
      underlying these phenomena are still poorly understood. Several small molecules
      acting as Axl inhibitors have been reported, and some of them are undergoing
      clinical investigation. In this review, we describe Axl biological functions, its
      expression in cancer and in drug-resistant tumor cells and the development of
      inhibitors tailored to this receptor tyrosine kinase. 

PMID- 27048337
TI  - Human Tuberculosis II. M. tuberculosis Mechanisms of Genetic and Phenotypic
      Resistance to Anti-Tuberculosis Drugs.
AB  - The great progress of knowledge of both M. tuberculosis physiology and how human
      host and bacilli interact has provided fertile ground for improving diagnosis and
      cure of TB infection. Once M. tuberculosis has infected humans, it elaborates
      strategies for evading the risk to killing by the cells of the host immune system
      and by the anti-tuberculosis (anti-TB) agents employed to cure infection. These
      strategies give rise to a bacterial multidrug resistance (MDR) status. This stems
      firstly from genetic mutations targeting a constellation of drug-processing
      mechanisms that still need full identification, as drug efflux pumps and drug
      activating/ inactivating enzymes (genetic resistance). Secondly, from the
      bacterial adaptation to stressful environmental conditions by adopting a
      temporary dormancy state lasting for decades and characterized by indifference to
      anti-TB drugs (phenotypic resistance or tolerance). The clarification of the
      strategies elaborated for surviving by M. tuberculosis has brought to the
      identification in the last few years of a number of mycobacterial molecular
      targets worth to exploitation for the development of novel and powerful anti-TB
      drugs. These targets include drug-efflux pump systems, considered partly
      responsible for genetic multi-drug resistance, and several enzymes and pump
      systems, as well, that sustain the metabolic adaptations of M. tuberculosis in
      the host and give rise to its phenotypic drug resistance. 

PMID- 27048338
TI  - Insights into the Structural Features Essential for JAK2 Inhibition and
      Selectivity.
AB  - The Janus kinase 2 (JAK2)-mediated signaling pathway plays an important role in
      controlling cell survival, proliferation, and differentiation. A mutation of JAK2
      (V617F in specific) that results in constitutive activation of the enzyme is
      found in patients with myeloproliferative neoplasms (MPNs), such as polycythemia
      vera (PV), essential thrombocythemia, and primary myelofibrosis. The genetic,
      biological, and physiological evidence available to date has established JAK2
      inhibitors as effective chemotherapeutic agents for the treatment of MPNs as well
      as solid tumors, hepatitis C virus (HCV) infection, Alzheimer's disease, and
      Parkinson's disease. Important features essential for JAK2 inhibitors are potent
      enzymatic inhibition and a high degree of selectivity among other isoforms of
      JAK. The extent of the potency and selectivity of JAK2 inhibitors is dependent
      upon receptor-ligand interactions and structural difference between isoenzymes.
      Thus, detailed knowledge regarding structural characteristics and the binding
      mode between JAK2 and its inhibitors is necessary. Accordingly, we compiled in
      this review a comprehensive summary of the three dimensional (3D) structural
      features of reported JAK2-ligand complexes and the structureactivity relationship
      (SAR) of JAK2 inhibitors, with particular focus on potent JAK2 inhibition and
      specificity. 

PMID- 27048339
TI  - Selecting Good 'Drug-Like' Properties to Optimize Small Molecule Blood-Brain
      Barrier Penetration.
AB  - The success rate to achieve clinical approval of drugs developed to treat
      diseases of the central nervous system (CNS) is the lowest of all disease
      indications. A large contributor to this poor success rate is failure of small
      molecules to pass through the blood-brain barrier (BBB), a barrier composed of
      capillary endothelial cells connected by tight junctions that functions to
      extrude xenobiotics from the brain. Designing small molecules to be BBB penetrant
      has been the subject of intensive research and has resulted in a series of
      guidelines to attain the best possible chances of BBB penetration. This review
      will analyze the current state of thinking in ranking the importance of various
      physicochemical properties required to select BBB penetrant molecules, describe
      model systems to determine BBB penetration, summarize data analysis methods and
      provide an outlook on further developments in the field. 

PMID- 27048340
TI  - Role of Vitamin D in Vascular Complications and Vascular Access Outcome in
      Patients with Chronic Kidney Disease.
AB  - Vitamin D has been known for a long time as a major factor involved in the
      calcium- phosphate balance and homeostasis, along with parathyroid hormone (PTH).
      While vitamin D effects on calcium and phosphate are fully known, recent studies
      attempted to link vitamin D status and cardiovascular diseases. The involvement
      of vitamin D on vascular remodeling is mediated by several mechanisms such as
      activation of renin-angiotensin-aldosterone system (RAAS), cell proliferation and
      anti-apoptotic cell pathways. This correlation is highlighted by the fact that
      the activated form of vitamin D (1,25 (OH)2 D3) can be synthesized by the same
      endothelial cells, due to the constitutive presence of endothelial 1alpha
      hydroxylase. Vitamin D reduces the expression of angiotensin 2 receptor (AT2R) on
      the endothelial cell surface (AT2R), leading to a cascade of events that result
      in the synthesis of vasodilators, such as nitric oxide. The activation of vitamin
      D receptors (VDRs) on endothelial cells induces changes in the metabolic activity
      of the endothelium and is responsible for cell survival, proliferation and
      neoangiogenesis. Moreover, altered signaling of VDR due to gene polymorphisms has
      been demonstrated in patients with cardiac disorders and chronic kidney disease
      (CKD). Recently, vascular access outcome has been associated with vitamin D
      status. Future studies will help to better define the need of vitamin D
      supplementation for a better cardiovascular as well as vascular access outcome in
      patients with CKD. 

PMID- 27048341
TI  - Zinc and Copper Homeostasis in Head and Neck Cancer: Review and Meta-Analysis.
AB  - Metals are known for playing essential roles in human physiology. Copper and zinc
      are trace elements closely dependent on one another and are involved in cell
      proliferation, growth, gene expression, apoptosis and other processes. Their
      homeostasis is crucial and tightly controlled by a resourceful system of
      transporters and transport proteins which deliver copper and zinc ions to their
      target sites. Abnormal zinc and copper homeostasis can be seen in a number of
      malignancies and also in head and neck cancer. Imbalance in this homeostasis is
      observed as an elevation or decrease of copper and zinc ions in serum or tissue
      levels in patients with cancer. In head and neck cancer these altered levels
      stand out from those of other malignancies which makes them an object of interest
      and therefore zinc and copper ions might be a good target for further research of
      head and neck cancer development and progression. This review aims to summarize
      the physiological roles of copper and zinc, its binding and transport mechanisms,
      and based on those, its role in head and neck cancer. To provide stronger
      evidence, dysregulation of levels is analysed by a meta-analytical approach. 

PMID- 27048342
TI  - Effect of Dipeptidyl Peptidase-4 Inhibitors on Plasma Adiponectin: A Systematic
      Review and Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND/OBJECTIVES: The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on
      plasma concentrations of adiponectin, a fat-derived hormone with anti-atherogenic
      and anti-inflammatory properties, is uncertain. A systematic review and meta
      analysis of randomized controlled trials (RCTs) was conducted to investigate this
      association in humans. METHODS: RCTs investigating the impact of DPP-4 inhibitors
      on plasma adiponectin concentrations were identified after searching PubMed
      Medline, SCOPUS, and Google Scholar databases (up to February 2015). As
      quantitative data synthesis methods, the random-effects model and the generic
      inverse variance method were applied. Standard methods of meta-regression,
      sensitivity analysis, and publication bias assessments were performed. RESULTS:
      Eight RCTs with nine treatment-arms were included. Meta-analysis did not suggest
      a significant pooled effect of DDP-4 inhibitors on adiponectin values (weighed
      mean-difference [WMD]: 0.19 MUg/mL, 95%CI: -0.50, 0.88). However, a significant
      elevation of plasma adiponectin concentrations was observed in the subset of
      trials with vildagliptin (WMD: 0.55 MUg/mL, 95%CI: 0.13, 0.98, p=0.010) but not
      sitagliptin (WMD: -0.06 MUg/mL, 95%CI: -1.13, 1.00, p=0.907). There was a
      significant elevation of plasma adiponectin levels in the subset of trials
      comparing DPP-4 inhibitors versus placebo or no treatment (WMD: 0.74 MUg/mL,
      95%CI: 0.36, 1.12, p <0.001) but not in the subset using hypoglycemic drugs as
      comparators), or using other hypoglycemic drugs (WMD: -0.18 MUg/mL, 95%CI: -0.99,
      0.62, p=0.654). No significant effect was found for treatment duration, confirmed
      by meta-regression analyses. CONCLUSION: DPP-4 inhibitors cause a significant
      increase in plasma adiponectin concentrations and this effect is greater with
      vildagliptin than sitagliptin.

PMID- 27048343
TI  - Advances in Nanocarriers for Anticancer Drugs Delivery.
AB  - Cancer is the most dangerous disease to haunt the mankind in the world today.
      Generally, the overall cancer mortality rates are similar in both the sexes. The
      reasons for most of these deaths are inefficacy and failure of the current
      methods of treatments or the unavailability of treatment options. The researchers
      of the world are actively integrating nanotechnology of treating of various
      cancers. The development of smart nanocarriers is one of the most important
      innovations in this direction. The nanocarriers of the different materials are
      being developed to improve the efficacy of current treatments. The present
      article describes the role of nanotechnology in cancer treatment emphasizing
      cancer nanotherapy, nanocarriers for drug delivery, types and the mechanisms of
      the nanocarriers. Besides, the efforts are made to discuss the recent advances in
      the nanocarriers, current challenges and the future prospective. 

PMID- 27048345
TI  - Validation of a New Placebo Interferential Current Method: A New Placebo Method
      of Electrostimulation.
AB  - Objective: The present study aimed to investigate if a new placebo device for
      interferential current (IFC) that delivers current during only the first 40
      seconds of stimulation is effective at promoting adequate subject blinding.
      Methods: Seventy-five subjects were recruited and enrolled into three groups:
      active IFC, inactive placebo, and new placebo. Pressure pain threshold (PPT),
      cutaneous sensory threshold (CST), and pain intensity were measured before and
      after the intervention. After the final assessment, the subjects and the
      investigator who applied the current were asked about the type of stimulation
      administered. Results: None of the placebo forms studied resulted in significant
      changes to PPT, CST, or pain intensity. The subjects stimulated with active IFC
      at high intensities (> 17 mA) of stimulation showed higher PPT and CST and lower
      pain intensity than subjects stimulated at low intensities ( p < 0.03). The new
      placebo method blinded the investigator in 100% of cases of IFC and 60% of
      subjects stimulated, whereas for inactive placebo, the investigator was blinded
      at a rate of 0% and 34% of subjects. Conclusion: The new method of placebo IFC
      was effective for blinding of research investigators and most of the active IFC
      treated subjects, promoting an appropriate placebo method.

PMID- 27048346
TI  - The 1-Year Treatment Course of New Opioid Recipients in Veterans Health
      Administration.
AB  - BACKGROUND: Understanding opioid prescribing trends requires differentiating
      clinically distinct short- and long-term receipt patterns. OBJECTIVES: Describe
      the one-year course of opioid receipt among new opioid recipients and determine
      the proportion with subsequent long-term opioid therapy. Discern variation in
      proportion with long-term therapy initiation by geographic region and across
      Veterans Health Administration (VHA) medical centers. METHODS: Longitudinal
      course of opioid receipt was analyzed using a cabinet supply approach. Short-term
      receipt was defined as index treatment episode lasting no longer than 30 days;
      long-term therapy as treatment episode of >90 days that began within the first 30
      days following opioid index date. PATIENTS: All VHA pharmacy users in 2004 and to
      2011 who received a new prescription for an opioid (incident opioid recipients)
      preceded by 365 days with no opioid prescribed. RESULTS: The proportion of all
      incident recipients who met the definition for long-term therapy within the first
      year decreased from 20.4% (N = 76,280) in 2004 to 18.3% (N = 96,166) in 2011. The
      proportion of incident recipients with chronic pain was unchanged between 2004
      and 2011. Hydrocodone and tramadol increased as a proportion of initial opioids
      prescribed. Median days initially supplied decreased from 30 to 20 days. A
      greater percentage of new opioid prescriptions were for 7 days or fewer (20.9% in
      2004; 27.9% in 2011). The proportion of new recipients who initiated long-term
      opioid therapy varied widely by medical center. Medical centers with higher
      proportions of new long-term recipients in 2004 saw greater decreases in this
      metric by 2011. CONCLUSION: The proportion of new opioid recipients who initiated
      long-term opioid therapy declined between 2004 and 2011.

PMID- 27048348
TI  - Alternatives to statins in intolerant patients do lower cholesterol, study finds.

PMID- 27048347
TI  - Liposomal Aerosols of Nitric Oxide (NO) Donor as a Long-Acting Substitute for the
      Ultra-Short-Acting Inhaled NO in the Treatment of PAH.
AB  - PURPOSE: This study seeks to develop a liposomal formulation of
      diethylenetriamine NONOate (DN), a long acting nitric oxide (NO) donor, with a
      goal to replace inhaled NO (iNO) in the treatment of pulmonary arterial
      hypertension (PAH). METHODS: Liposomal formulations were prepared by a lipid film
      hydration method and modified with a cell penetrating peptide, CAR. The particles
      were characterized for size, polydispersity index (PDI), zeta potential,
      entrapment efficiency, storage and nebulization stability, and in-vitro release
      profiles. The cellular uptake and transport were assessed in rat alveolar
      macrophages (NR8383) and transforming growth factor beta (TGF-beta) activated rat
      pulmonary arterial smooth muscle cells (PASMCs). The fraction of the formulation
      that enters the systemic circulation, after intratracheal administration, was
      determined in an Isolated Perfused Rat Lung (IPRL) model. The safety of the
      formulations were assessed using an MTT assay and by measuring injury markers in
      the bronchoalveolar lavage (BAL) fluid; the pharmacological efficacy was
      evaluated by monitoring the changes in the mean pulmonary arterial (mPAP) and
      systemic pressure (mSAP) in a monocrotaline (MCT) induced-PAH rat model RESULTS:
      Liposome size, zeta potential, and entrapment efficiency were 171 +/- 4 nm, -37
      +/- 3 mV, and 46 +/- 5%, respectively. The liposomes released 70 +/- 5% of the
      drug in 8 h and were stable when stored at 4 degrees C. CAR-conjugated-liposomes
      were taken up more efficiently by PASMCs than liposomes-without-CAR; the uptake
      of the formulations by rat alveolar macrophages was minimal. DN-liposomes did not
      increase lung weight, protein quantity, and levels of injury markers in the BAL
      fluid. Intratracheal CAR-liposomes reduced the entry of liposomes from the lung
      to blood; the formulations produced a 40% reduction in mPAP for 180 minutes.
      CONCLUSION: This study establishes the proof-of-concept that peptide modified
      liposomal formulations of long-acting NO donor can be an alternative to short
      acting iNO.

PMID- 27048349
TI  - Genic insights from integrated human proteomics in GeneCards.
AB  - GeneCards is a one-stop shop for searchable human gene annotations
      (http://www.genecards.org/). Data are automatically mined from ~120 sources and
      presented in an integrated web card for every human gene. We report the
      application of recent advances in proteomics to enhance gene annotation and
      classification in GeneCards. First, we constructed the Human Integrated Protein
      Expression Database (HIPED), a unified database of protein abundance in human
      tissues, based on the publically available mass spectrometry (MS)-based
      proteomics sources ProteomicsDB, Multi-Omics Profiling Expression Database,
      Protein Abundance Across Organisms and The MaxQuant DataBase. The integrated
      database, residing within GeneCards, compares favourably with its individual
      sources, covering nearly 90% of human protein-coding genes. For gene annotation
      and comparisons, we first defined a protein expression vector for each gene,
      based on normalized abundances in 69 normal human tissues. This vector is
      portrayed in the GeneCards expression section as a bar graph, allowing visual
      inspection and comparison. These data are juxtaposed with transcriptome bar
      graphs. Using the protein expression vectors, we further defined a pairwise
      metric that helps assess expression-based pairwise proximity. This new metric for
      finding functional partners complements eight others, including sharing of
      pathways, gene ontology (GO) terms and domains, implemented in the GeneCards
      Suite. In parallel, we calculated proteome-based differential expression,
      highlighting a subset of tissues that overexpress a gene and subserving gene
      classification. This textual annotation allows users of VarElect, the suite's
      next-generation phenotyper, to more effectively discover causative disease
      variants. Finally, we define the protein-RNA expression ratio and correlation as
      yet another attribute of every gene in each tissue, adding further annotative
      information. The results constitute a significant enhancement of several
      GeneCards sections and help promote and organize the genome-wide structural and
      functional knowledge of the human proteome. Database
      URL:http://www.genecards.org/.

PMID- 27048350
TI  - Lisdexamfetamine: A Review in ADHD in Adults.
AB  - Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting amfetamine
      prodrug with a convenient once-daily oral regimen that offers the potential for
      improved adherence and reduced abuse compared with short-acting preparations of
      amfetamines. Lisdexamfetamine (as Elvanse Adult((r)); Tyvense AdultTM) has been
      approved for use in adults with attention-deficit hyperactivity disorder (ADHD)
      under the EU decentralization procedure, with the first approvals in the UK,
      Sweden and Denmark. This approval reflects the results of three short-term trials
      in adults with ADHD in which fixed- or flexible-dose lisdexamfetamine produced
      significantly greater improvements than placebo in ADHD symptoms, overall
      functioning, executive functioning (including in patients with significant pre
      existing impairment) and quality of life. Of note, a post hoc analysis of one of
      these studies suggested that the response to lisdexamfetamine was generally
      similar in treatment-naive patients and those who had already received-and not
      responded satisfactorily to-previous ADHD therapies, including methylphenidate
      (MPH). Two further studies demonstrated the longer-term effectiveness of flexible
      dose lisdexamfetamine in reducing ADHD symptoms, albeit maintenance of efficacy
      required ongoing treatment with the drug. Lisdexamfetamine was generally well
      tolerated in clinical trials, with an adverse event profile typical of that
      reported for other long-acting stimulants. Head-to-head comparisons with other
      long-acting agents, notably MPH and atomoxetine, are lacking. Nonetheless, on the
      basis of the available data, lisdexamfetamine provides a useful alternative
      option for the treatment of adults with ADHD, including those who have not
      responded adequately to previous ADHD therapies, including MPH. 

PMID- 27048352
TI  - Ghost-Pill-Buster: A Case Study of Intact Levetiracetam Extended-Release Tablets
      after Dissolution Testing.
AB  - BACKGROUND: Orally administered medications in extended-release (ER) dosage forms
      continue to play a pivotal role in the treatment of various central nervous
      system disorders. For certain ER dosage forms, pharmaceutical scientists have
      been familiar with the passage of intact tablet-like objects in patients' feces
      after administration of ER tablets or capsules based on water-insoluble or slowly
      dissolving excipients. Nevertheless, because of lack of awareness of the "ghost
      pill" phenomenon, anxiety has ensued among some patients and clinicians, who have
      less understanding of how drugs are released from these tablets once ingested. It
      has been brought to the attention of the US Food and Drug Administration (FDA)
      that epilepsy patients administered with Teva's levetiracetam ER tablets have
      noticed intact tablets in their stools and been concerned that they were not
      getting the needed dose of the drug. In response to neurologists' clinical
      reporting, the FDA has conducted investigations to confirm a minimal risk of
      incomplete drug release of Teva's drug product. OBJECTIVE: The objective of this
      study was to evaluate the risks of incomplete drug release associated with the
      passing of intact levetiracetam ER tablets, by conducting in vitro dissolution
      testing. METHODS: Dissolution testing of Teva's drug product was performed in
      accordance with the US Pharmacopeia monograph for levetiracetam ER tablets in
      phosphate buffer and bio-relevant buffers at different pH values. In addition,
      dissolution testing was conducted with split and crushed tablets. At the end of
      the dissolution testing, all samples were visually inspected for any undissolved
      pieces. RESULTS: Approximately 90 % of levetiracetam had been released in all
      dissolution media after 8 h of dissolution. The levetiracetam ER tablets after
      dissolution testing remained fully intact in all dissolution media. The rates of
      drug release were significantly faster from split and crushed tablets than that
      from whole tablets. CONCLUSION: On the basis of these findings, Teva's
      levetiracetam ER tablets may appear intact in the stools but have released the
      drug successfully. The FDA has requested Teva to revise its product labeling to
      include remarks regarding the potential passing of intact tablets. Since patients
      who notice ghost pills in their stools may impetuously crush or split the tablets
      of subsequent doses on their own, healthcare providers should instruct patients
      to swallow whole tablets throughout the treatment, in accordance with the drug
      label.

PMID- 27048351
TI  - Unexplained Painful Physical Symptoms in Patients with Major Depressive Disorder:
      Prevalence, Pathophysiology and Management.
AB  - Patients with major depression often report pain. In this article, we review the
      current literature regarding the prevalence and consequences, as well as the
      pathophysiology, of unexplained painful physical symptoms (UPPS) in patients with
      major depressive disorder (MDD). UPPS are experienced by approximately two-thirds
      of depressed patients. The presence of UPPS makes a correct diagnosis of
      depression more difficult. Moreover, UPPS are a predictor of a poor response to
      treatment and a more chronic course of depression. Pain, in the course of
      depression, also has a negative impact on functioning and quality of life.
      Frequent comorbidity of depression and UPPS has inspired the formulation of an
      hypothesis regarding a shared neurobiological mechanism of both conditions.
      Evidence from neuroimaging studies has shown that frontal-limbic dysfunction in
      depression may explain abnormal pain processing, leading to the presence of UPPS.
      Increased levels of proinflamatory cytokines and substance P in patients with MDD
      may also clarify the pathophysiology of UPPS. Finally, dysfunction of the
      descending serotonergic and noradrenergic pathways that normally suppress
      ascending sensations has been proposed as a core mechanism of UPPS. Psychological
      factors such as catastrophizing also play a role in both depression and chronic
      pain. Therefore, pharmacological treatment and/or cognitive therapy are
      recommended in the treatment of depression with UPPS. Some data suggest that
      serotonin and noradrenaline reuptake inhibitors (SNRIs) are more effective than
      selective serotonin reuptake inhibitors (SSRIs) in the alleviation of depression
      and UPPS. However, the pooled analysis of eight randomised clinical trials showed
      similar efficacy of duloxetine (an SNRI) and paroxetine (an SSRI) in reducing
      UPPS in depression. Further integrative studies examining genetic factors (e.g.
      polymorphisms of genes for interleukins, serotonin transporter and receptors),
      molecular factors (e.g. cytokines, substance P) and neuroimaging findings (e.g.
      functional studies during painful stimulation) might provide further explanation
      of the pathophysiology of UPPS in MDD and therefore facilitate the development of
      more effective methods of treatment. 

PMID- 27048353
TI  - Pharmacologic Treatment of Pediatric Hypertension.
AB  - Prevalence of hypertension is increasing in children and adolescents.
      Uncontrolled hypertension in children not only causes end organ damage but also
      increases the risk of adult hypertension and cardiovascular disease. Clinical
      trials have proven efficacy of antihypertensive medications in children. These
      medications are well tolerated by children with acceptable safety profile. The
      choice of agent is usually driven by underlying etiology of hypertension, profile
      of its side effects, and clinician's preference. This article will review
      currently available pediatric data on mechanism of action, common adverse
      effects, pediatric indication, recent clinical trial, and newer drugs in the
      common classes of antihypertensive medications. 

PMID- 27048354
TI  - Quality of life of high-functioning children and youth with autism spectrum
      disorder and typically developing peers: Self- and proxy-reports.
AB  - Studies have shown parents to report lower quality of life for their children
      with autism spectrum disorder than children's self-report scores and the same
      applies for data on typically developing children. Our objectives were to: (1)
      explore how high-functioning children with autism spectrum disorder rate their
      quality of life compared with paired controls without autism spectrum disorder;
      (2) explore how parents of high-functioning children with autism spectrum
      disorder rate their children's quality of life compared with parents of paired
      controls; and (3) compare child self-reports of quality of life with their
      parent's proxy-reports for both groups of children. Data were collected with the
      Icelandic self- and proxy-reported versions of the KIDSCREEN-27. Reports of 96
      children with autism spectrum disorder, 211 controls and their parents were
      included in the analyses. Compared with controls, children with autism spectrum
      disorder had lower means on all quality of life dimensions. Parents of children
      with autism spectrum disorder evaluated their children's quality of life lower on
      all dimensions than did parents of controls. On four out of five dimensions,
      children with autism spectrum disorder reported better quality of life than did
      their parents. Despite differences in ratings children with autism spectrum
      disorder and their parents agreed on the most problematic dimensions, namely,
      social support and peers and physical well-being. Our results highlight the
      importance of seeking the viewpoints of both children and their parents.

PMID- 27048355
TI  - Young children with autism spectrum disorders imitate in the context of others'
      prior intention.
AB  - Many studies have shown that children with autism spectrum disorder have some
      understanding of intentions behind others' goal-directed actions on objects. It
      is not clear whether they understand intentions at a high level of abstraction
      reliant on the context in which the actions occur. This study tested their
      understanding of others' prior intentions with typically developing and
      developmentally delayed children. We replicated Carpenter et al.'s test of the
      ability to understand prior intentions embedded in the social situation with an
      additional context of no prior intention. Results showed that when the
      experimenter's intention was made known before the demonstration, children
      without autism spectrum disorder performed not only better than the autism
      spectrum disorder children but also better than themselves when there was no
      information about prior intention. No between-condition difference was found in
      the autism spectrum disorder group. It thus appears that children with autism
      spectrum disorder have difficulty decoupling intentions from the context of the
      situation. The present findings, together with previous evidence for the
      intactness of the ability to understand and to imitate goal-directed actions,
      suggest that asymmetrical imitation performance occurs at different levels of
      understanding of intention by children with autism spectrum disorder.

PMID- 27048356
TI  - Can PPH3 be helpful to assess the discordant grade in primary and metastatic
      enteropancreatic neuroendocrine tumors?
AB  - Therapeutic strategy in neuroendocrine tumors (NETs) is based on histological
      characteristics of the primary tumor (PT), even in case of metastatic disease.
      Our aim was to compare the tumor grade between PT and their liver metastases (LM)
      in patients with enteropancreatic NETs. Forty-one patients treated for sporadic
      NETs (10 pancreatic, 31 intestinal) were included. All presented synchronous (35)
      or metachronous (6) LM. Tumor grade was evaluated for PT and LM according to the
      WHO classification, using Ki-67 labeling and mitotic count (MC) evaluated with or
      without phospho-histone H3 (PPH3). Tumor grade differed between primary and
      metastatic tumor in 16/41 patients (39 %), with an increase of grade in 13 of
      them (32 %). The median Ki-67, MC, and PPH3 in metastases were statistically
      higher than in PT (p = 0.0002, 0.02, and 0.01). In 17 of 65 cases tested with
      PPH3 (26 %), this antibody was more efficient in assessing the grade compared to
      the usual MC, and in 2/65 cases compared to the Ki-67. A better correlation was
      observed between Ki-67 and PPH3 (p = 0.0001) than between Ki-67 and MC without
      immunohistochemistry. There is a significant difference in tumor grade between
      primary and metastatic NETs, underlining the necessity of a systematic biopsy on
      LM for patient management. Moreover, PPH3 appears to be a powerful antibody to
      assess the MC and the tumor grade much more accurately when associated with Ki
      67. 

PMID- 27048357
TI  - Structured therapeutic education in diabetes: is it time to re-write the chapter
      on the prevention of diabetic complications?

PMID- 27048358
TI  - Structured nursing educational programs improve quality of life outcomes in
      patients with Cushing's syndrome.

PMID- 27048360
TI  - National Association for Patient Participation (NAPP) replies to article on
      patient participation groups in general practice.

PMID- 27048359
TI  - Ophthalmic artery originating from the anterior cerebral artery: anatomo
      radiological study, histological analysis, and literature review.
AB  - The ophthalmic artery has an anomalous origin in 2-3 % of cases and rarely arises
      from the anterior cerebral artery. Herein, we provide the first anatomical,
      radiological, and histological description of such an anomalous origin, together
      with a literature review. During the anatomical dissection of an 81-year-old
      Caucasian male, the absence of the right ophthalmic artery in its usual location
      was evident from an endonasal transsphenoidal perspective. The specimen was then
      studied in detail, through multiple dissections, corrosion casting, high
      resolution CT, and histological analysis. The English literature on anomalous
      origins of the ophthalmic artery was reviewed, together with reported associated
      pathologies. Anatomo-radiological analysis documented that the right ophthalmic
      artery arose from the inferior surface of A1 tract of the anterior cerebral
      artery (A1) and passed over the optic nerve in its subarachnoid tract. A meningo
      ophthalmic artery was evident on the same side and reached the orbit through the
      superior orbital fissure. Histological examination of both internal carotid
      artery (ICA) walls documented a significantly decreased thickness of the tunica
      media and adventitia on the side of the anomalous ophthalmic artery, with a
      significantly different content of collagen types I and III. The literature
      review documented an association of aneurysms and anomalous ophthalmic arteries.
      To the best of our knowledge, this is the first anatomical report that includes a
      radiological and arterial wall analysis of a persistent ventral ophthalmic
      artery. The latter provides histological data that support the clinical evidence
      of a higher association of aneurysms with anomalous origins of the ophthalmic
      artery. 

PMID- 27048361
TI  - Inhibition of BMP and of TGFbeta receptors downregulates expression of XIAP and
      TAK1 leading to lung cancer cell death.
AB  - BACKGROUND: Bone morphogenetic proteins (BMP) are embryonic proteins that are
      part of the transforming growth factor (TGFbeta) superfamily, which are
      aberrantly expressed in many carcinomas. Inhibition of BMP receptors with small
      molecule inhibitors decreases growth and induces death of lung cancer cells,
      which involves the downregulation of Id1 and Id3 by a Smad dependent mechanism.
      Developmentally, BMP and TGFbeta signaling utilizes Smad-1/5 independent
      mechanisms to stabilize the expression of X-linked inhibitor of apoptosis protein
      (XIAP) and activate TGFbeta activated kinase 1 (TAK1), which are known to be
      potent inhibitors of apoptosis. The role of BMP signaling in regulating XIAP and
      TAK1 in cancer cells is poorly understood. Furthermore, the interaction between
      the BMP and TGFbeta signaling cascades in regulating the activation of TAK1 in
      cancer cells has not been elucidated. METHODS: Feedback regulation between the
      BMP and TGFbeta signaling pathways and their regulation of XIAP, TAK1, and Id1
      were examined in lung cancer cells utilizing siRNA and inhibitors targeting BMP
      type I receptors, inhibitors of BMP and TGFbeta type I receptors, and an
      inhibitor of BMP and TGFbeta type I and type II receptors. RESULTS: We show that
      upon inhibition of BMP signaling in lung cancer cells, the TGFbeta signaling
      cascade is activated. Both the BMP and TGFbeta pathways activate TAK1, which then
      increases the expression of Id1. Inhibition of TGFbeta signaling increased Id1
      expression except when BMP signaling is suppressed, which then causes a dose
      related decrease in the expression of Id1. Inhibition of both BMP and TGFbeta
      signaling enhances the downregulation of TAK1. Our data also suggests that the
      blockade of the BMP type II receptor enhances the downregulation XIAP, which is
      important in decreasing the activity of TAK1. Knockdown studies demonstrate that
      both XIAP and TAK1 regulate the survival of lung cancer cells. CONCLUSIONS: This
      paper highlights that targeting the BMP and TGFbeta type I and type II receptors
      causes a downregulation of XIAP, TAK1, and Id1 leading to cell death of lung
      cancer cells. Small molecule inhibitors targeting the BMP and TGFbeta receptors
      represents a potential novel means to treat cancer patients.

PMID- 27048362
TI  - Case reports in medical education: a platform for training medical students,
      residents, and fellows in scientific writing and critical thinking.
AB  - A case report is a detailed narrative that usually illustrates a diagnostic or
      therapeutic problem experienced by one or several patients. Case reports commonly
      serve as the first line of evidence for new interventions or they function as
      alarms that an issue exists with an already established therapy. Case reports are
      of minor importance in evidence-based medicine; however, they make meaningful
      contributions to both the knowledge and education of medical students, residents,
      and fellows. Case reports are written with the goal of sharing information for
      medical, scientific, or educational purposes. They often serve as medical or even
      undergraduate students' first experience with medical writing and they provide a
      solid foundation for manuscript preparation and publication. In the last few
      decades, there has been an exponential increase in medical student research,
      specifically in the number of manuscripts published by medical students. It is
      important to foster this academic spirit among students by encouraging them to
      become involved in research. This editorial will focus on the value and
      educational benefits of writing case reports for medical students, university
      students, residents, and fellows. 

PMID- 27048364
TI  - Prognostic impact of tumour-associated B cells and plasma cells in epithelial
      ovarian cancer.
AB  - BACKGROUND: The critical role of the immune system in controlling cancer
      progression has become evident and immune modulatory therapy is now approved for
      clinical use. However, while the majority of studies on the inflammatory tumour
      microenvironment have focused on the cellular immune response, in particular the
      prognostic and predictive role of various T cell infiltrates, the role of the
      humoral immune response in this context has long been overlooked. This study
      aimed to investigate the clinicopathological correlates and prognostic impact of
      B cell and plasma cell infiltration in epithelial ovarian cancer (EOC). METHODS:
      Immunohistochemical expression of immunoglobulin kappa C (IGKC), CD20 and CD138
      was analysed in tissue microarrays with tumours from 154 incident cases of EOC
      from two pooled prospective population-based cohorts. Subsets of corresponding
      benign-appearing fallopian tubes (n = 38) and omental metastases (n = 33) were
      also analysed. Kaplan-Meier analysis and Cox regression analysis were used to
      determine the impact of immune-cell specific IGKC, CD20 and CD138 expression on
      overall survival and ovarian cancer-specific survival. RESULTS: High IGKC
      expression correlated significantly with expression of CD20 (p = 0.001) and CD138
      (p = 0.035). Expression of IGKC as well as CD138 was significantly higher in
      primary tumours than in fallopian tubes (p = 0.004 and p = 0.001, respectively).
      High CD20 and CD138 expression correlated significantly with high tumour grade (p
      = 0.032 and p = 0.030, respectively). CD20 and IGKC expression was not prognostic
      but univariable Cox regression analysis revealed high CD138 expression to
      correlate with a significantly reduced overall survival (HR = 2.20; 95 % CI 1.34
      3.55; p-0.001) as well as ovarian cancer-specific survival (HR = 1.95; 95 % CI
      1.28-2.98; p = 0.002). The prognostic impact was independent of established
      clinical parameters (age, grade, clinical stage) as shown in multivariable
      analysis (HR = 2.28; 95 % CI 1.39-3.75; p = 0.001). CONCLUSIONS: In conclusion,
      our results demonstrate that plasma cell infiltration in epithelial ovarian
      cancer has a significant impact on tumour progression and prognosis. The
      important role of the humoral immune system merits further study and may be
      harnessed as immune modulatory strategies in cancer therapy.

PMID- 27048363
TI  - Neuroradiologic characteristics of astroblastoma and systematic review of the
      literature: 2 new cases and 125 cases reported in 59 publications.
AB  - BACKGROUND: Astroblastoma is a rare tumor of uncertain origin most commonly
      presenting in the cerebrum of children and young adults. The literature contains
      only case reports and small series regarding its radiologic features. This
      systematic review is the largest study of imaging findings of astroblastoma to
      date and serves to identify features that might differentiate it from other
      neoplasms. OBJECTIVE: This study describes the imaging features of astroblastoma
      based on a systematic review of the literature and two new cases. MATERIALS AND
      METHODS: We conducted a PubMed and Google Scholar database search that identified
      59 publications containing 125 cases of pathology-confirmed astroblastoma, and we
      also added two new cases from our own institution. Data collected include patient
      age, gender, tumor location, morphology, calcifications and calvarial changes. We
      recorded findings on CT, MRI, diffusion-weighted imaging (DWI), MR spectroscopy,
      positron emission tomography (PET) and catheter angiography. RESULTS: Age at
      diagnosis ranged 0-70 years (mean 18 years; median 14 years). Female-to-male
      ratio was 8:1. Of 127 cases, 66 reported CT, 78 reported MRI and 47 reported both
      findings. Not all authors reported all features, but the tumor features reported
      included supratentorial in 96% (122/127), superficial in 72% (48/67), well
      demarcated in 96% (79/82), mixed cystic-solid in 93% (79/85), and enhancing in
      99% (78/79). On CT, 84% (26/31) of astroblastomas were hyperattenuated, 73%
      (27/37) had calcifications and 7 cases reported adjacent calvarial erosion.
      Astroblastomas were hypointense on T1-W in 58% (26/45) and on T2-W in 50% (23/46)
      of MRI sequences. Peritumoral edema was present in 80% (40/50) of cases but was
      typically described as slight. Six cases included DWI findings, with 100% showing
      restricted diffusion. On MR spectroscopy, 100% (5/5) showed nonspecific tumor
      spectra with elevated choline and decreased N-acetylaspartate (NAA). PET revealed
      nonspecific reduced uptake of [F-18] 2-fluoro-2-deoxyglucose ((18)F-FDG) and
      increased uptake of [11C]-Methionine in 100% (3/3) of cases. Catheter angiography
      findings (n=12) were variable, including hypervascularity in 67%, arteriovenous
      shunting in 33% and avascular areas in 25%. CONCLUSION: Astroblastomas occur most
      often in adolescent girls. Imaging often shows a supratentorial, superficial,
      well-defined, cystic-solid enhancing mass. On CT, most are hyperattenuated, have
      calcifications, and may remodel adjacent bone if superficial. MRI
      characteristically reveals a hypointense mass on T1-W and T2-W sequences with
      restricted diffusion. MR spectroscopy, PET and catheter angiography findings are
      nonspecific.

PMID- 27048365
TI  - The association of hand preference and sensation seeking behavior.
AB  - SUMMARY: Although the human body shows a superficial symmetry, the disparate
      functions and skills of both body halves lead to an asymmetrical use. As a
      result, lateral preferences are detectable, which also include the favoured use
      of one hand ('handedness'). The collection of questionnaire data on sensation
      seeking and the conduction of behavioral handedness tasks by 55 research
      participants enabled the investigation of the interaction of handedness and
      sensation seeking. For this procedure the age-homogeneous study population is
      divided according to the Handedness-Index (HI) - a calculated value, indicating
      the practical hand preference. The results reveal a stronger lateralization in
      right-handed participants as well as a difference in the mean value of hand use
      in the three handedness groups. Sensation seeking behavior shows significant
      negative correlations with age as well as with the HI. Higher scores of left
      handers in Experience Seeking (ES), Sensation Seeking (SS) as well as in Thrill
      and Adventure Seeking (TAS) indicate a larger risk investment in this handedness
      group. Hence, the results of this study suggest that handedness is a strong
      indicator of risk behavior.

PMID- 27048366
TI  - Fellowships and subspecialization in anesthesia: Are they good, bad, or both?

PMID- 27048367
TI  - In Reply: Fellowships and subspecialization in anesthesia: Are they good, bad, or
      both?

PMID- 27048368
TI  - Modified McCall culdoplasty versus Shull suspension in pelvic prolapse primary
      repair: a retrospective study.
AB  - INTRODUCTION AND HYPOTHESIS: Uterosacral ligament suspension at the time of
      primary prolapse repair represents a well-established surgical option. Our aim
      was to compare the effectiveness, complications rate, and functional results of
      modified McCall culdoplasty and Shull suspension. METHODS: Patients who underwent
      vaginal hysterectomy and cuff suspension for pelvic organ prolapse were
      retrospectively analyzed. McCall culdoplasty (group A) or Shull suspension (group
      B) were performed according to surgeon choice based on age and sexual activity.
      Perioperative data, objective, and subjective cure rate were noted. RESULTS: A
      total of 339 patients (215 in group A and 124 in group B) completed follow-up.
      Operating time and blood loss were slightly higher in group B. The complications
      rate was similar in the two groups. Anatomical outcomes in terms of recurrence
      and reoperation rate did not show any statistically significant differences. POP
      Q items analysis revealed only a different total vaginal length between groups (8
      mm longer in group B). Functional outcomes were similar in the two groups as was
      patient satisfaction. CONCLUSION: Both uterosacral ligament suspension procedures
      were shown to be safe and effective. There were no clinically significant
      differences with regard to surgical data, complications, anatomical, functional,
      and subjective outcomes between modified McCall culdoplasty and Shull suspension.

PMID- 27048369
TI  - Oryza sativa H+-ATPase (OSA) is Involved in the Regulation of Dumbbell-Shaped
      Guard Cells of Rice.
AB  - The stomatal apparatus consists of a pair of guard cells and regulates gas
      exchange between the leaf and atmosphere. In guard cells, blue light (BL)
      activates H(+)-ATPase in the plasma membrane through the phosphorylation of its
      penultimate threonine, mediating stomatal opening. Although this regulation is
      thought to be widely adopted among kidney-shaped guard cells in dicots, the
      molecular basis underlying that of dumbbell-shaped guard cells in monocots
      remains unclear. Here, we show that H(+)-ATPases are involved in the regulation
      of dumbbell-shaped guard cells. Stomatal opening of rice was promoted by the H(+)
      ATPase activator fusicoccin and by BL, and the latter was suppressed by the H(+)
      ATPase inhibitor vanadate. Using H(+)-ATPase antibodies, we showed the presence
      of phosphoregulation of the penultimate threonine in Oryza sativa H(+)-ATPases
      (OSAs) and localization of OSAs in the plasma membrane of guard cells.
      Interestingly, we identified one H(+)-ATPase isoform, OSA7, that is
      preferentially expressed among the OSA genes in guard cells, and found that loss
      of function of OSA7 resulted in partial insensitivity to BL. We conclude that
      H(+)-ATPase is involved in BL-induced stomatal opening of dumbbell-shaped guard
      cells in monocotyledon species. 

PMID- 27048370
TI  - Coping with the economic burden of Diabetes, TB and co-prevalence: evidence from
      Bishkek, Kyrgyzstan.
AB  - BACKGROUND: The increasing number of patients co-affected with Diabetes and TB
      may place individuals with low socio-economic status at particular risk of
      persistent poverty. Kyrgyz health sector reforms aim at reducing this burden,
      with the provision of essential health services free at the point of use through
      a State-Guaranteed Benefit Package (SGBP). However, despite a declining trend in
      out-of-pocket expenditure, there is still a considerable funding gap in the SGBP.
      Using data from Bishkek, Kyrgyzstan, this study aims to explore how households
      cope with the economic burden of Diabetes, TB and co-prevalence. METHODS: This
      study uses cross-sectional data collected in 2010 from Diabetes and TB patients
      in Bishkek, Kyrgyzstan. Quantitative questionnaires were administered to 309
      individuals capturing information on patients' socioeconomic status and a range
      of coping strategies. Coarsened exact matching (CEM) is used to generate socio
      economically balanced patient groups. Descriptive statistics and logistic
      regression are used for data analysis. RESULTS: TB patients are much younger than
      Diabetes and co-affected patients. Old age affects not only the health of the
      patients, but also the patient's socio-economic context. TB patients are more
      likely to be employed and to have higher incomes while Diabetes patients are more
      likely to be retired. Co-affected patients, despite being in the same age group
      as Diabetes patients, are less likely to receive pensions but often earn income
      in informal arrangements. Out-of-pocket (OOP) payments are higher for Diabetes
      care than for TB care. Diabetes patients cope with the economic burden by using
      social welfare support. TB patients are most often in a position to draw on
      income or savings. Co-affected patients are less likely to receive social welfare
      support than Diabetes patients. Catastrophic health spending is more likely in
      Diabetes and co-affected patients than in TB patients. CONCLUSIONS: This study
      shows that while OOP are moderate for TB affected patients, there are severe
      consequences for Diabetes affected patients. As a result of the underfunding of
      the SGBP, Diabetes and co-affected patients are challenged by OOP. Especially
      those who belong to lower socio-economic groups are challenged in coping with the
      economic burden.

PMID- 27048371
TI  - Sustained Implementation Support Scale: Validation of a Measure of Program
      Characteristics and Workplace Functioning for Sustained Program Implementation.
AB  - An evaluation measure of enablers and inhibitors to sustained evidence-based
      program (EBP) implementation may provide a useful tool to enhance organizations'
      capacity. This paper outlines preliminary validation of such a measure. An expert
      informant and consumer feedback approach was used to tailor constructs from two
      existing measures assessing key domains associated with sustained implementation.
      Validity and reliability were evaluated for an inventory composed of five
      subscales: Program benefits, Program burden, Workplace support, Workplace
      cohesion, and Leadership style. Exploratory and confirmatory factor analysis with
      a sample of 593 Triple P-Positive Parenting Program-practitioners led to a 28
      item scale with good reliability and good convergent, discriminant, and
      predictive validity. Practitioners sustaining implementation at least 3 years
      post-training were more likely to have supervision/peer support, reported higher
      levels of program benefit, workplace support, and positive leadership style, and
      lower program burden compared to practitioners who were non-sustainers.

PMID- 27048372
TI  - Genetic differentiation within and away from the chromosomal rearrangements
      characterising hybridising chromosomal races of the western house mouse (Mus
      musculus domesticus).
AB  - The importance of chromosomal rearrangements for speciation can be inferred from
      studies of genetic exchange between hybridising chromosomal races within species.
      Reduced fertility or recombination suppression in karyotypic hybrids has the
      potential to maintain or promote genetic differentiation in genomic regions near
      rearrangement breakpoints. We studied genetic exchange between two hybridising
      groups of chromosomal races of house mouse in Upper Valtellina (Lombardy, Italy),
      using microsatellites. These groups differ by Robertsonian fusions and/or whole
      arm reciprocal translocations such that F1 hybrids have a chain-of-five meiotic
      configuration. Previous studies showed genetic differentiation in two chromosomes
      in the chain-of-five (10 and 12) close to their centromeres (i.e. the
      rearrangement breakpoints); we have shown here that the centromeric regions of
      the other two chromosomes in the chain (2 and 8) are similarly differentiated.
      The internal chromosomes of the chain (8 and 12) show the greatest
      differentiation, which may reflect pairing and recombination properties of
      internal and external elements in a meiotic chain. Importantly, we found that
      centromeric regions of some non-rearranged chromosomes also showed genetic
      differentiation between the hybridising groups, indicating a complex interplay
      between chromosomal rearrangements and other parts of the genome in maintaining
      or promoting differentiation and potentially driving speciation between
      chromosomal races.

PMID- 27048373
TI  - Is adherence therapy an effective adjunct treatment for patients with
      schizophrenia spectrum disorders? A systematic review and meta-analysis.
AB  - BACKGROUND: Poor adherence to medication in schizophrenia spectrum disorders
      leads to inadequate symptom control. Adherence therapy (AT) is an intervention
      that seeks to reduce patients' psychiatric symptoms by enhancing treatment
      adherence. We aimed to systematically review the trial evidence of the
      effectiveness of AT on improving clinical outcomes in these patients. METHOD:
      Systematic review and meta-analysis of published RCTs. We included studies
      testing AT as an adjunct intervention against treatment as usual or a comparator
      intervention in the general adult psychiatric population. The primary outcome of
      interest was improvement in psychiatric symptoms. RESULTS: We included six
      studies testing AT in schizophrenia spectrum disorders published since 2006. A
      meta-analysis showed AT significantly reduced psychiatric symptoms compared to
      usual treatment over a follow-up period of less than 1 year. We found no
      significant effects of AT on patients' adherence and adherence attitudes.
      CONCLUSIONS: AT is an effective adjunctive treatment for people with
      schizophrenia spectrum disorders. PROSPERO: CRD42015016779.

PMID- 27048374
TI  - Social/economic costs and quality of life in patients with haemophilia in Europe.
AB  - OBJECTIVE: The aim of this study was to determine the economic burden from a
      societal perspective and the health-related quality of life (HRQOL) of patients
      with haemophilia in Europe. METHODS: We conducted a cross-sectional study of
      patients with haemophilia from Bulgaria, France, Germany, Hungary, Italy, Spain
      Sweden and the UK. Data on demographic characteristics, health resource
      utilisation, informal care, loss of labour productivity and HRQOL were collected
      from the questionnaires completed by patients or their caregivers. HRQOL was
      measured with the EuroQol 5-domain (EQ-5D) questionnaire. The costs have been
      estimated from a societal perspective adopting a bottom-up approach. RESULTS: A
      total of 401 questionnaires were included in the study, of which 339 were
      collected from patients with haemophilia and 62 from caregivers. The lowest
      average annual cost per person was reported in Bulgaria (?6,660) and the highest
      in Germany (?194,490). Our results demonstrate both a large difference from
      country to country in the average annual cost per patient in 2012 and the driving
      role of drugs in costs. Drugs represent nearly 90 % of direct healthcare costs in
      a majority of the countries analysed (Hungary, Italy, Spain and Germany). In
      Bulgaria, France and Sweden, however, healthcare services (visits, tests and
      hospitalisations) prevail. Costs are also shown to differ between children and
      adults. The mean EQ-5D index score for adult patients was 0.69 and mean EQ-5D VAS
      was 66.6. The mean EQ-5D index score for carers was 0.87 and mean EQ-5D VAS was
      75.5. In the disability score, 60 % showed no disability and measuring caregiver
      burden with the Zarit Index produced an overall mean score of 25.3. CONCLUSION:
      We have shown that haemophilia is associated with a substantial economic burden
      and impaired HRQOL. Studies on cost of illness and HRQOL are important for
      haemophilia as the future of this disease is likely to change with the
      development of new innovative treatments. The introduction of these treatments
      will most likely impact future costs related to haemophilia.

PMID- 27048376
TI  - Preclinical Models of Multiple Sclerosis: Advantages and Limitations Towards
      Better Therapies.
AB  - Multiple sclerosis (MS) is a disease of the central nervous system (CNS) with an
      unknown etiology. MS complex pathophysiology-characterized by CNS inflammation,
      demyelination and axonal injury-has made its modeling in experimental systems
      particularly problematic. Moreover, the evidence that MS does not naturally occur
      in other species has further complicated MS preclinical studies. Through the
      years, several MS in vivo models have been developed. Experimental autoimmune
      encephalomyelitis (EAE) represents the most widely used MS experimental model and
      relies upon the autoimmune paradigm to explore MS neuropathology. Although EAE
      has been instrumental in understanding the molecular events which take place upon
      neuroinflammation, not all MS hallmarks can be efficiently shaped within this
      conceptual frameshift. Thus, alternative models of CNS demyelination have been
      characterized, either based on viral infection or neurotoxin administration.
      However imperfect, these models have greatly improved our knowledge of the immune
      system&#039;s function in health and disease. On the other side, their intrinsic
      distance from MS has often led to misinterpreting and overestimating the data
      gleaned from these experimental systems. In this review, each model will be
      discussed in the light of its potentiality to mimic MS and translate the most
      promising therapies to patients. In addition, we will address how new genomic
      technologies can help improve the existing models. 

PMID- 27048375
TI  - Shared genetic control of expression and methylation in peripheral blood.
AB  - BACKGROUND: Expression QTLs and epigenetic marks are often employed to provide an
      insight into the possible biological mechanisms behind GWAS hits. A substantial
      proportion of the variation in gene expression and DNA methylation is known to be
      under genetic control. We address the proportion of genetic control that is
      shared between these two genomic features. RESULTS: An exhaustive search for
      pairwise phenotypic correlations between gene expression and DNA methylation in
      samples from human blood (n = 610) was performed. Of the 5 * 10(9) possible
      pairwise tests, 0.36 % passed Bonferroni corrected p-value cutoff of 9.9 * 10(
      12). We determined that the correlation structure between probe pairs was largely
      due to blood cell type specificity of the expression and methylation probes. Upon
      adjustment of the expression and methylation values for observed blood cellular
      composition (n = 422), the number of probe pairs which survived Bonferroni
      correction reduced by more than 5400 fold. Of the 614 correlated probe pairs
      located on the same chromosome, 75 % share at least one methylation and
      expression QTL at nominal 10(-5) p-value cutoff. Those probe pairs are located
      within 1Mbp window from each other and have a mean of absolute value of genetic
      correlation equal to 0.69, further demonstrating the high degree of shared
      genetic control. CONCLUSIONS: Overall, this study demonstrates notable genetic
      covariance between DNA methylation and gene expression and reaffirms the
      importance of correcting for cell-counts in studies on non-homogeneous tissues.

PMID- 27048377
TI  - Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and
      Multiple Diseases.
AB  - The calcium binding protein S100B has attracted great attention as a biomarker
      for a variety of diseases. S100B is mainly expressed in glial cells and functions
      through intracellular and extracellular signaling pathways. The biological roles
      of S100B have been closely associated with its concentrations and its
      physiological states. The released S100B can bind to the receptor of advanced
      glycation end products and induce the initiation of multiple cell signaling
      transductions. The regulation of S100B bioactivities has been suggested through
      phosphoinositide 3 kinase/Akt, p53, mitogen-activated protein kinases,
      transcriptional factors including nuclear factor-kappaB, and cyclic adenosine
      monophosphate. The levels of S100B in the blood may function to predict the
      progress or the prognosis of many kinds of diseases, such as cerebrovascular
      diseases, neurodegenerative diseases, motor neuron diseases, traumatic brain
      injury, schizophrenia, depression, diabetes mellitus, myocardial infarction,
      cancer, and infectious diseases. Given that the activity of S100B has been
      implicated in the pathological process of these diseases, S100B should not be
      simply regarded as a biomarker, it may also function as therapeutic target for
      these diseases. Further elucidation of the roles of S100B may formulate
      innovative therapeutic strategies for multiple diseases. 

PMID- 27048378
TI  - Prospects of Bacteriotherapy with Nanotechnology in Nanoparticledrug Conjugation
      Approach for Cancer Therapy.
AB  - Bacteriotherapy and nanotechnology have shown remarkable potential in diagnostic
      and therapeutic applications for various diseases. Individual impacts of these
      micro-nano systems over different aspects of human health are well studied;
      however, an integrated system of bacteria-nanoparticle (NP) conjugation is less
      explored. The untamed potential of bacteria-NP conjugation could be a new tool
      for diagnosis and treatment of invasive diseases like malaria, tuberculosis and
      cancer. Mammalian cells exhibit cytosis as their defense mechanism when they
      encounter foreign elements such as bacteria. In these mammalian cells, during
      phagocytosis, bacteria are ruptured and lysed by lysozymes. A bacterium carrying
      the drug-tagged NP would be engulfed in the same manner and ultimately reaches
      the target cells. Rapid and continuous cell divisions in the cancer tissues lead
      to defective vessels, underdeveloped cellcell interconnects, development of
      hypoxic areas and heterogeneous population of tumor cells. This unorganized and
      poorly developed angiogenesis in tumor cells makes it difficult for conventional
      chemotherapeutic drugs to localize the tumors selectively. In the present
      scenario of diagnosis and treatment of cancer/tumor cells, it could be expected
      that the existing bacteriotherapy with the advanced nanotechnology would be a way
      further in the targeted drug delivery for cancer therapy. This review emphasizes
      the potential applications of bacteriotherapy with nanotechnology for the
      diagnosis and treatment of cancer. 

PMID- 27048379
TI  - Natural AMPK Activators: An Alternative Approach for the Treatment and Management
      of Metabolic Syndrome.
AB  - This review covers recent discoveries of phytoconstituents, herbal extracts and
      some semi-synthetic compounds for treating metabolic syndrome with AMPK
      activation as one of their mechanisms of action. Recent researches have
      demonstrated AMPK activation to ameliorate multiple components of metabolic
      syndrome by regulating a balance between anabolic and catabolic cellular
      reactions. The review attempts to delineate the AMPK activation by natural agents
      from the perspective of its functional consequences on enzymes, transcription
      factors and signaling molecules and also on other potential factors contributing
      in the amelioration of metabolic syndrome.

PMID- 27048380
TI  - Modulation of Expression and Activity of ABC Transporters by the Phytoestrogen
      Genistein. Impact on Drug Disposition.
AB  - ATP binding cassette (ABC) transporters are involved in drug absorption,
      distribution and elimination. They also mediate multidrug resistance in cancer
      cells. Isoflavones, such as genistein (GNT), belong to a class of naturally
      occurring compounds found at high concentrations in commonly consumed soya based
      foods and dietary supplements. GNT and its metabolites interact with ABC
      transporters as substrates, inhibitors and/or modulators of their expression.
      This review compiles information about regulation of ABC transporters by GNT with
      special emphasis on the three major groups of ABC transporters involved in
      excretion of endo- and xenobiotics as follows: Pglycoprotein (MDR1, ABCB1), a
      group of multidrug resistance associated proteins (MRPs, ABCC subfamily) and
      ABCG2 (BCRP), an ABC half-transporter. The impact of these regulations on
      potential GNT-drug interactions is further considered. 

PMID- 27048381
TI  - Abrogation of Nrf2 impairs antioxidant signaling and promotes atrial hypertrophy
      in response to high-intensity exercise stress.
AB  - BACKGROUND: Anomalies in myocardial structure involving myocyte growth,
      hypertrophy, differentiation, apoptosis, necrosis etc. affects its function and
      render cardiac tissue more vulnerable to the development of heart failure.
      Although oxidative stress has a well-established role in cardiac remodeling and
      dysfunction, the mechanisms linking redox state to atrial cardiomyocyte
      hypertrophic changes are poorly understood. Here, we investigated the role of
      nuclear erythroid-2 like factor-2 (Nrf2), a central transcriptional mediator, in
      redox signaling under high intensity exercise stress (HIES) in atria. METHODS:
      Age and sex-matched wild-type (WT) and Nrf2(-/-) mice at >20 months of age were
      subjected to HIES for 6 weeks. Gene markers of hypertrophy and antioxidant
      enzymes were determined in the atria of WT and Nrf2(-/-) mice by real-time qPCR
      analyses. Detection and quantification of antioxidants, 4-hydroxy-nonenal (4
      HNE), poly-ubiquitination and autophagy proteins in WT and Nrf2(-/-) mice were
      performed by immunofluorescence analysis. The level of oxidative stress was
      measured by microscopical examination of di-hydro-ethidium (DHE) fluorescence.
      RESULTS: Under the sedentary state, Nrf2 abrogation resulted in a moderate down
      regulation of some of the atrial antioxidant gene expression (Gsr, Gclc, Gstalpha
      and Gstu) despite having a normal redox state. In response to HIES, enlarged
      atrial myocytes along with significantly increased gene expression of
      cardiomyocyte hypertrophy markers (Anf, Bnf and beta-Mhc) were observed in Nrf2(
      /-) when compared to WT mice. Further, the transcript levels of Gclc, Gsr and
      Gstu and protein levels of NQO1, catalase, GPX1 were profoundly downregulated
      along with GSH depletion and increased oxidative stress in Nrf2(-/-) mice when
      compared to its WT counterparts after HIES. Impaired antioxidant state and
      profound oxidative stress were associated with enhanced atrial expression of LC3
      and ATG7 along with increased ubiquitination of ATG7 in Nrf2(-/-) mice subjected
      to HIES. CONCLUSIONS: Loss of Nrf2 describes an altered biochemical phenotype
      associated with dysregulation in genes related to redox state, ubiquitination and
      autophagy in HIES that result in atrial hypertrophy. Therefore, our findings
      direct that preserving Nrf2-related antioxidant function would be one of the
      effective strategies to safeguard atrial health.

PMID- 27048383
TI  - Simvastatin-induced cognitive dysfunction: two case reports.
AB  - BACKGROUND: Simvastatin is commonly prescribed for hypercholesterolemia to reduce
      vascular risk in patients. Some of these patients have dementia with cognitive
      defects of several domains. Although protective effects seem to be present, there
      is emerging evidence that statins cause cognitive impairment. The role of
      cholesterol in cognitive function is complex. This is reflected in the effects
      that statins show on cognition functions. The reduction in cholesterol levels
      seen with statins is effective in improving learning and memory in some patients.
      However, there is emerging evidence that statins may worsen cognitive function.
      Similarly, there are major concerns over whether statins alleviate or worsen
      cognitive problems. The correlation between cholesterol levels and cognitive
      function is still controversial, mainly due to a lack of robust evidence. CASE
      PRESENTATION: We report the cases of two Asian patients who developed cognitive
      deficits after starting simvastatin. A 32-year-old man and a 54-year-old woman
      developed different but clear cognitive deficits that reversed after stopping
      simvastatin. CONCLUSIONS: The possibility of new-onset cognitive dysfunction and
      the deterioration of existing cognitive deficits should be considered when
      prescribing simvastatin to patients.

PMID- 27048382
TI  - Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the
      dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic
      systems of neonatal female rats.
AB  - BACKGROUND: Long-chain polyunsaturated fatty acids (PUFAs) are major components
      of the phospholipids that forming the cell membrane. Insufficient availability of
      PUFAs during prenatal period decreases accretion of docosahexaenoic acid (DHA) in
      the developing brain. DHA deficiency is associated with impaired attention and
      cognition, and would precipitate psychiatric symptoms. However, clinical studies
      on the potential benefits of dietary DHA supplementation to neural development
      have yielded conflicting results. METHODS: To further investigate the
      neurochemical influence of maternal PUFAs levels, we assessed the functioning of
      various neurotransmitter systems including glutamatergic, dopaminergic,
      norepinephrinergic and serotoninergic systems in the brain of neonatal female
      rats by HPLC-MS/MS. Meanwhile, the cell proliferation of neonatal rats was
      investigated using immunefluorescence. RESULTS: Different maternal n-3 PUFAs
      dietary influenced the FA composition, cell proliferation in the dentate gyrus of
      hippocampus and the contents of gamma-aminobutyric acid (GABA), glutamine (GLN),
      dopamine (DA) and its metabolites [3,4- dihydroxyphenyl acetic acid (DOPAC) and
      homovanillic acid (HVA)], norepinephrine (NE), vanilmandelic acid (VMA) and 5-HT
      turnover in the brain of neonatal rats. However, the mRNA expression of key
      synthase of neurotransmitters remains stable. CONCLUSIONS: Our study showed that
      maternal deficiency of n-3 PUFAs might play an important role in central nervous
      system of neonatal female rats mainly through impairing the normal neurogenesis
      and influencing glutamatergic system and 5-HT turnover.

PMID- 27048384
TI  - The potential of single-cell profiling in plants.
AB  - Single-cell transcriptomics has been employed in a growing number of animal
      studies, but the technique has yet to be widely used in plants. Nonetheless,
      early studies indicate that single-cell RNA-seq protocols developed for animal
      cells produce informative datasets in plants. We argue that single-cell
      transcriptomics has the potential to provide a new perspective on plant problems,
      such as the nature of the stem cells or initials, the plasticity of plant cells,
      and the extent of localized cellular responses to environmental inputs. Single
      cell experimental outputs require different analytical approaches compared with
      pooled cell profiles and new tools tailored to single-cell assays are being
      developed. Here, we highlight promising new single-cell profiling approaches,
      their limitations as applied to plants, and their potential to address
      fundamental questions in plant biology. 

PMID- 27048385
TI  - Identification of downstream target genes regulated by the nitric oxide-soluble
      guanylate cyclase-cyclic guanosine monophosphate signal pathway in pulmonary
      hypertension.
AB  - OBJECTIVE: To investigate the downstream target genes regulated by the nitric
      oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP)
      signal pathway and their possible roles in the pathogenesis of pulmonary
      hypertension (PH). METHODS: Digital gene expression tag profiling was performed
      to identify genes that are differentially expressed after activation of the NO
      sGC-cGMP signal pathway in human pulmonary artery smooth muscles cells using 8
      bromo-cyclic guanosine monophosphate, BAY 41-2272 and BAY 60-2770. Results were
      confirmed using real-time polymerase chain reaction. Gene ontology and signal
      transduction network analyses were also performed. RESULTS: A number of genes
      were differentially expressed, including MMP1, SERPINB2, GREM1 and IL8. A total
      of 68 gene ontology terms and seven pathways were found to be associated with
      these genes. Most of these genes are involved in cell proliferation, cell
      migration and apoptosis, which may contribute to the pathological pulmonary
      vascular remodelling in PH. CONCLUSION: These results may provide new insights
      into the molecular mechanisms of PH.

PMID- 27048386
TI  - The effect of anticancer therapy on anti-hepatitis B antibody titres in patients
      with haematological malignancies and solid tumours.
AB  - OBJECTIVE: To investigate the effect of immunosuppressive anticancer therapy on
      titre levels of anti-hepatitis B surface antibodies (anti-HBs) in hepatitis B
      surface antigen (HBsAg) negative and anti-HBs positive patients with
      haematological malignancies or solid tumours. METHODS: This retrospective study
      reviewed the medical records of patients with haematological malignancies or
      solid tumours. Pretreatment HBsAg negative and anti-HBs positive patients were
      included in the analysis. Anti-hepatitis B core antibody status was used to
      evaluate vaccinated patients and those with resolved HBV infections. RESULTS: The
      medical records of 237 patients were reviewed retrospectively. The median anti
      HBs titre decreased significantly after anticancer therapy compared with the
      pretreatment median anti-HBs titre in all patients (71 mIU/ml versus 57 mIU/ml).
      Anti-HBs titre decreased significantly in patients with haematological
      malignancies (70 mIU/m versus 37 mIU/ml) and in patients administered rituximab
      based chemotherapy (67 mIU/ml versus 33 mIU/ml) following chemotherapy, whereas
      there was no significant change in patients with solid tumours. After
      chemotherapy, patients with low pretreatment anti-HBs titres (<100 mIU/ml) were
      more likely to become seronegative (<10 mIU/ml). CONCLUSION: High levels of anti
      HBs may have a protective effect against the reactivation of HBV especially in
      patients with haematological malignancies who received immunosuppressive
      anticancer therapy.

PMID- 27048387
TI  - Impact of effect-site concentration of propofol on cardiac systolic function
      assessed by tissue Doppler imaging.
AB  - OBJECTIVE: To evaluate the relationship between effect-site concentration (CE) of
      propofol during total intravenous anaesthesia (TIVA) and cardiac systolic
      function using tissue Doppler imaging (TDI) in patients undergoing cardiovascular
      procedures. METHODS: Stepwise increments of CE of propofol of 1.0, 2.0, 3.0 and
      4.0 ug/ml (modified Marsh model) were achieved using a target-controlled infusion
      device. Transthoracic echocardiographic assessments using TDI were performed for
      each CE of propofol and corresponding systolic myocardial velocity (s'), mean
      arterial blood pressure (MAP), heart rate (HR) and bispectral index (BIS) were
      evaluated. RESULTS: Data from 31 patients were analysed in this prospective
      study. The s' velocity decreased with increasing propofol CE and values recorded
      at propofol CE 3.0 and 4.0 ug/ml were near or below 8 cm/s indicating abnormal
      cardiac systolic function. MAP, HR and BIS also decreased with each propofol CE
      increment. CONCLUSION: Although the recommended dosage for propofol is up to 4.0
      ug/ml, caution should be taken when using propofol concentrations above 2.0 ug/ml
      during TIVA in patients with underlying cardiovascular diseases.

PMID- 27048388
TI  - The development of a personalized patient education tool for decision making for
      postmenopausal women with osteoporosis.
AB  - A personalized patient education tool for decision making (PET) for
      postmenopausal women with osteoporosis was developed by means of a systematic
      development approach. A prototype was constructed and refined by involving
      various professionals and patients. Professionals and patients expressed a
      positive attitude towards the use of the PET. INTRODUCTION: The purpose was to
      systematically develop a paper-based personalized PET to assist postmenopausal
      women with osteoporosis in selecting a treatment in line with their personal
      values and preferences. METHODS: The development of the PET was based on a
      systematic process including scope, design, development of a prototype, and alpha
      testing among professionals and patients by semi-structured interviews. RESULTS:
      The design and development resulted in a four-page PET prototype together with a
      one-page fact sheet of the different drug options. The prototype PET provided the
      personal risk factors, the estimated individualized risk for a future major
      osteoporotic fracture and potential reduction with drugs, and a summary of
      advantages and disadvantages whether or not to start drugs. The drug fact sheet
      presents five attributes of seven drugs in a tabular format. The alpha testing
      with professionals resulted in some adaptations, e.g., inclusion of the
      possibility to calculate fracture risk based on various individual risk scoring
      methods. Important results from the alpha testing with patients were differences
      in the fracture risk percentage which was seen as worthwhile to start drugs, the
      importance of an overview of side effects, and of the timing of the PET into the
      patient pathway. All women indicated that the PET could be helpful for their
      decision to select a treatment. CONCLUSION: Physicians and patients expressed a
      positive attitude towards the use of the proposed PET. Further research would be
      needed to test the effects of the PET on feasibility in clinical workflow and on
      patient outcomes.

PMID- 27048389
TI  - The effect of prolonged breast-feeding on the development of postmenopausal
      osteoporosis in population with insufficient calcium intake and vitamin D level.
AB  - Breast-feeding affects bone metabolism and calcium homeostasis, and prolonged
      breast-feeding may influence the development of postmenopausal osteoporosis,
      particularly in highly susceptible populations. The study determined that breast
      feeding may be a risk factor for postmenopausal osteoporosis, especially in
      people with low calcium intakes and vitamin D deficiencies. INTRODUCTION: The
      purpose of this study was to determine whether breast-feeding is a risk factor in
      the development of postmenopausal osteoporosis, especially in highly susceptible
      population. METHODS: The study was performed using data from the 2010 to 2011
      Korea National Health and Nutrition Examination Survey, and it included 1231
      postmenopausal women who were aged between 45 and 70 years. Osteoporosis was
      defined using the World Health Organization's T-score criteria, namely, a T-score
      of <=-2.5 at the femoral neck or the lumbar spine. The patients' ages, body mass
      indexes, daily calcium intakes, serum vitamin D levels, exercise levels, smoking
      histories, and reproductive factors relating to menarche, menopause, delivery,
      breast-feeding, hormone treatment, and oral contraceptive use were evaluated.
      Comparisons between the osteoporosis and non-osteoporosis groups were undertaken
      using Student's t test and the chi-square test, and logistic regression models
      were built. RESULTS: A significant increase in the risk of osteoporosis was
      apparent in postmenopausal women with prolonged breast-feeding histories (>=24
      months) (model 1: odds ratio [OR] = 2.489; 95 % confidence interval [CI] = 1.111
      to 5.578, p = 0.027; model 2: OR = 2.503; 95 % CI = 1.118 to 5.602, p = 0.026;
      model 3: OR = 2.825; 95 % CI = 1.056 to 7.56, p = 0.039), particularly in those
      with inadequate serum vitamin D levels and calcium intakes (<800 mg/day).
      CONCLUSIONS: Breast-feeding seems to increase the risk of postmenopausal
      osteoporosis; however, its impact may not be definitive in women with sufficient
      vitamin D levels and calcium intakes. Therefore, sufficient calcium intakes and
      adequate vitamin D levels may be important to prevent osteoporosis in
      postmenopausal women that is derived from breast-feeding.

PMID- 27048390
TI  - The formation of extracellular potentials over the innervation zone: Are these
      potentials affected by changes in fibre membrane properties?
AB  - Widespread misconceptions still exist regarding the formation of extracellular
      potentials over the innervation zone: the assumption (1) that the first phase of
      these potentials mainly reflects the process of initiation of the intracellular
      action potential (IAP) at the neuromuscular junction and that (2) these
      potentials are not sensitive to changes in fibre membrane properties (such as
      changes in the IAP length). Here, we examined the peculiarities of the
      extracellular potentials detected over the innervation region with the aim to
      clarify whether the changes in membrane properties are reflected in the amplitude
      of these potentials. These goals were addressed using a biophysical model of the
      IAP as well as a convolutional model of EMG generation. Also, the theoretical
      predictions made by these models were verified experimentally. We showed that
      only the initial portion of the potentials detected over the innervation zone
      corresponded to the origination of the IAP at the junction: the remaining (final)
      portion resulted from the propagation of the IAP along the fibre. It was found
      that, as radial distance increases, the portion of the rising phase with
      "propagating character" increased its duration, whereas the duration of the
      portion with "standing character" remained unchanged. Moreover, a lengthening of
      the IAP profile resulted in a distinct increase in the amplitude of the first
      phase of these potentials. These findings were confirmed experimentally and
      demonstrate that changes in fibre membrane properties influence the amplitude of
      surface EMG potentials recorded over the innervation zone to the same extent as
      they do surface potentials recorded elsewhere along the length of the muscle
      fibres.

PMID- 27048391
TI  - Numerical simulation on the effects of drug-eluting stents with different bending
      angles on hemodynamics and drug distribution.
AB  - Implantation of drug-eluting stents in curved blood vessels may cause changes in
      hemodynamics and drug distribution, and even provoke in-stent restenosis. Due to
      the complexity of building three-dimensional (3-D) curved stent model, few
      studies have gone through such numerical simulations. In this study, three
      virtual stent models with different bending angles (0 degrees , 30 degrees  and
      90 degrees ) were developed to numerically investigate the distribution of wall
      shear stress (WSS) and drug concentration. The results showed that (1) the low
      WSS regions in the inner bend of the stent models increased with the bending
      angles; (2) the drug concentration differed between the inner and outer bends of
      the stents but irrespective to the changes of bending angle; (3) the pattern of
      drug concentration for the curved stents found similar to that of the straight
      stents, and the phenomenon, 'proximal part low and distal part high' in the drug
      concentration showed in both the straight and curved stents. The increase in
      bending angles from 30 degrees  to 90 degrees  had little effect on the WSS and
      drug concentration; however, the largest effect of the curved stents was the
      remarkable difference of drug concentration between the inner and outer bends of
      the stents-about 20 %. Hence, it is feasible that quick analysis focused on the
      straight stents instead of the curved stents.

PMID- 27048392
TI  - NHS staff launch judicial review against junior contract imposition.

PMID- 27048393
TI  - Engaging Older Adults in Health Care Decision-Making: A Realist Synthesis.
AB  - BACKGROUND: Engagement in healthcare decision making has been recognized as an
      important, and often lacking, aspect of care, especially in the care of older
      adults who are major users of the healthcare system. OBJECTIVE: We aimed to
      conduct a review of available knowledge on engagement in healthcare decision
      making with a focus on older patients and their caregivers. METHODS: We conducted
      a realist synthesis focusing on strategies for engagement of older patients and
      their caregivers in healthcare decision making. The synthesis encompassed
      theoretical frameworks and both peer-reviewed and grey literature. Expert
      consultations included interviews (n = 2) with academics and group consultations
      (n = 3) with older adults and their caregivers. Abstracts that reported
      description, assessment, or evaluation of strategies for engagement of adult
      patients, families, or caregivers (i.e., that report on actual experiences of
      engagement) were included. RESULTS: The search generated 15,683 articles, 663 of
      which were pertinent to healthcare decision making. Theoretical and empirical
      work identified a range of strategies and levels of engagement of older patients
      and their families in healthcare decision making. The importance of communication
      emerged as a key recommendation for meaningful engagement among providers and
      patients and their caregivers. The principles developed in this study should be
      implemented with consideration of the context in which care is being provided.
      CONCLUSIONS: We have developed a framework that promotes the engagement of
      patients and their caregivers as equal partners in healthcare decision making.
      Future research should implement and test the framework in various clinical
      settings.

PMID- 27048394
TI  - Shifts in plant foliar and floral metabolomes in response to the suppression of
      the associated microbiota.
AB  - BACKGROUND: The phyllospheric microbiota is assumed to play a key role in the
      metabolism of host plants. Its role in determining the epiphytic and internal
      plant metabolome, however, remains to be investigated. We analyzed the Liquid
      Chromatography-Mass Spectrometry (LC-MS) profiles of the epiphytic and internal
      metabolomes of the leaves and flowers of Sambucus nigra with and without external
      antibiotic treatment application. RESULTS: The epiphytic metabolism showed a
      degree of complexity similar to that of the plant organs. The suppression of
      microbial communities by topical applications of antibiotics had a greater impact
      on the epiphytic metabolome than on the internal metabolomes of the plant organs,
      although even the latter changed significantly both in leaves and flowers. The
      application of antibiotics decreased the concentration of lactate in both
      epiphytic and organ metabolomes, and the concentrations of citraconic acid,
      acetyl-CoA, isoleucine, and several secondary compounds such as terpenes and
      phenols in the epiphytic extracts. The metabolite pyrogallol appeared in the
      floral epiphytic community only after the treatment. The concentrations of the
      amino acid precursors of the ketoglutarate-synthesis pathway tended to decrease
      in the leaves and to increase in the foliar epiphytic extracts. CONCLUSIONS:
      These results suggest that anaerobic and/or facultative anaerobic bacteria were
      present in high numbers in the phyllosphere and in the apoplasts of S. nigra. The
      results also show that microbial communities play a significant role in the
      metabolomes of plant organs and could have more complex and frequent mutualistic,
      saprophytic, and/or parasitic relationships with internal plant metabolism than
      currently assumed.

PMID- 27048395
TI  - Prehospital volume resuscitation--Did evidence defeat the crystalloid dogma? An
      analysis of the TraumaRegister DGU(r) 2002-2012.
AB  - BACKGROUND: Various studies have shown the deleterious effect of high volume
      resuscitation following severe trauma promoting coagulopathy by haemodilution,
      acidosis and hypothermia. As the optimal resuscitation strategy during
      prehospital trauma care is still discussed, we raised the question if the amount
      and kind of fluids administered changed over the recent years. Further, if less
      volume was administered, fewer patients should have arrived in coagulopathic
      depletion in the Emergency Department resulting in less blood product
      transfusions. METHODS: A data analysis of the 100 489 patients entered into the
      TraumaRegister DGU(r) (TR-DGU) between 2002 and 2012 was performed of which a
      total of 23512 patients (23.3%) matched the inclusion criteria. Volume and type
      of fluids administered as well as outcome parameter were analysed. RESULTS:
      Between 2002 and 2012, the amount of volume administered during prehospital
      trauma care decreased from 1790 ml in 2002 to 1039 ml in 2012. At the same time
      higher haemoglobin mean values, higher Quick's mean values and reduced mean aPTT
      can be observed. Simultaneously, more patients received catecholamines (2002: 9.2
      to 2012: 13.0%). Interestingly, the amount of volume administered decreased
      steadily regardless of the presence of shock. Fewer patients were in the need of
      blood products and the number of massive transfusions (>=10 pRBC) more than
      halved. DISCUSSION: The changes in volume therapy might have reduced
      haemodilution potentially resulting in an increase of the Hb value. During the
      period observed transfusion strategies have become more restrictiveand ratio
      based; the percentage of patients receiving MT halved as blood products may imply
      negative secondary effects. Furthermore, preventing administration of high blood
      product ratios result in less impairment of coagulation factors and inhibitors
      and an therfore improved coagulation. CONCLUSION: The volume administered in
      severely injured patients decreased considerably during the last decade possibly
      supporting beneficial effects such as minimizing the risk of coagulopathy and
      avoiding potential harmful effects caused by blood product transfusions. Despite
      outstanding questions in trauma resuscitation, principle evidence merges quickly
      into clinical practice and algorithms.

PMID- 27048396
TI  - Sphenoid mucocele with unusual panhypopituitarism.
AB  - A 13-year-old boy presented with bilateral progressive proptosis, abduction
      deficit, optic atrophy and features suggestive of hypopituitarism secondary to a
      sphenoid sinus mucocele. Drainage of the mucocele along with hormone replacement
      therapy resulted in improvement in visual acuity and abduction. 

PMID- 27048397
TI  - Diminution of falsely elevated tumour markers following immunosuppression for
      systemic lupus erythematosus with neurological involvement.
AB  - We describe the case of a patient with a long history of undifferentiated
      connective tissue disease who developed headache, ataxia and orofacial dyskinesia
      attributed to a diagnosis of systemic lupus erythematosus (SLE). Gross elevation
      of the concentration of several plasma tumour markers (CEA, CA-125, CA19-9, CA15
      3) was detected in the absence of malignancy. These markers fell significantly
      within a month of starting immunosuppressive therapy alongside clinical
      improvement. Caution should be taken in the interpretation of plasma tumour
      markers in patients with connective tissue disease. 

PMID- 27048398
TI  - Primary antiphospholipid syndrome, hypertrophic non-obstructive cardiomyopathy
      and hypotelorism.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder associated with
      arterial/venous thrombosis. Cardiac manifestations of APS include valve
      stenosis/insufficiency, coronary artery disease and myocardial dysfunction
      presenting as dilated cardiomyopathy. In the following report, we present the
      case of a man with primary APS, hypertrophic non-obstructive cardiomyopathy and
      hypotelorism-a combination that has not yet been reported in the literature. 

PMID- 27048399
TI  - Front to back ocular injury from a vaping-related explosion.
AB  - We describe a case of extensive ocular injury secondary to an electronic
      cigarette (e-cigarette)-related explosion. The explosion was the result of
      modifications made to a heating element of the e-cigarette device by a non
      professional. Extensive ocular injuries that result from an explosion of an e
      cigarette device can potentially cause significant and permanent visual
      impairment. 

PMID- 27048400
TI  - Efficacy of immunosuppressive treatment in a systemic lupus erythematosus patient
      presenting with inclusion body myositis.
AB  - Inclusion body myositis (IBM) is an inflammatory myopathy that is generally
      unresponsive to immunosuppressive drugs. The coexistence of IBM with other
      autoimmune connective tissue diseases is rare. We present a case of a 76-year-old
      woman with systemic lupus erythematosus (SLE) who developed proximal muscle
      weakness of lower extremities and mild elevation of serum creatine kinase (CK) at
      495 U/L. Muscle biopsy showed changes of endomysial inflammation and rimmed
      vacuoles consistent with IBM. She was treated with prednisone 40 mg daily and
      methotrexate 12.5 mg weekly. One month later, her physical examination showed
      minimal proximal weakness of lower extremities. CK levels decreased to 44 U/L.
      Prednisone dose was gradually decreased to 5.0 mg daily. She remained stable with
      normal CK levels during a follow-up period of 10 months. This case, together with
      other reports, suggests that IBM in the setting of SLE represents a different
      subtype that can benefit from immunosuppressive treatment.

PMID- 27048401
TI  - MR dacryocystography: comparison with dacryoendoscopy in positional diagnosis of
      nasolacrimal duct obstruction.
AB  - PURPOSE: To compare the findings of MR dacryocystography with those of
      dacryoendoscopy and subsequent surgery in patients with nasolacrimal duct
      obstruction, and to determine the efficacy of MR dacryocystography in the
      positional diagnosis of nasolacrimal duct obstruction. MATERIALS AND METHODS:
      Thirty-one patients with clinically suspected nasolacrimal duct obstruction who
      underwent MR dacryocystography and dacryoendoscopy with subsequent surgical
      procedure were included. MR dacryocystography was performed by using heavily T2
      weighted fast spin echo sequence in the coronal and axial planes after the
      topical administration of normal saline drops into the conjunctival sacs.
      RESULTS: In MR dacryocystography, stenosis/obstruction at the canalicular level
      was correctly diagnosed in nine patients (100 %). Stenosis/obstruction at the
      lacrimal sac level was correctly diagnosed in 14 of 16 patients (87.5 %) in MR
      dacryocystography. Three patients with coexistent stenosis/obstruction at both
      the canalicular and the lacrimal sac level were misinterpreted as
      stenosis/obstruction at the canalicular level on MR dacryocystography. The
      overall accuracy of MR dacryocystography in depicting stenosis/obstruction was 84
      %. CONCLUSIONS: MR dacryocystography after the topical administration of normal
      saline drops into the conjunctival sacs is a well-tolerated, minimally invasive
      imaging technique to identify the level of stenosis/obstruction in patients with
      nasolacrimal duct obstruction before dacryoendoscopy and subsequent surgery.

PMID- 27048402
TI  - Lymph node ratio as parameter of regional lymph node involvement in pancreatic
      cancer.
AB  - PURPOSE: To determine which indicators, anatomical nodal metastasis (Japan
      Pancreas Society, JPS), number of positive lymph nodes (PLN), or lymph node ratio
      (LNR), is the best means of assessing lymph node involvement in pancreatic
      cancer. METHODS: This retrospective study analyzed 275 patients with pancreatic
      cancer treated at a single institution. Survival curves according to the JPS,
      PLN, or LNR were assessed by the Kaplan-Meier method. Prognostic value of each
      classification was explored by Cox regression analysis after adjustments for
      clinical factors. RESULTS: Multivariate analysis showed that, relative to n0 in
      the JPS, hazard ratios (HR) in n1, n2, and n3 were 1.72, 1.73, and 2.75,
      respectively, with no difference in survival between n1 and n2. Relative to PLN
      of 0, the HR in the PLN categories of 1~2, 3, and >3 were 1.39, 1.65, and 3.03,
      respectively. Relative to LNR of 0, the HR in the categories of 0 < LNR <= 0.1,
      0.1 < LNR <= 0.2, and LNR > 0.2 were 1.27, 2.00, and 5.58, respectively. An
      incremental increase in the HR was observed as the LNR category progressed, and
      differences between the survivals were distinct when stratified by the LNR.
      CONCLUSIONS: The LNR was an accurate predictor of survival among three assessment
      strategies and could be proposed as a candidate for use as N categories, pending
      validation studies.

PMID- 27048403
TI  - Cystic lesions of the pancreas-is radical surgery really warranted?
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate diagnostic
      accuracy of cystic lesions of the pancreas in order to determine if less
      aggressive surgical treatment might be safe and therefore warranted. METHODS: A
      retrospective cohort study was conducted in 232 patients with either observed or
      resected cystic lesions of the pancreas referred for evaluation and treatment to
      the University Medical Center Freiburg, Germany, between 2001 and 2011. RESULTS:
      Most patients had MRI or CT for preoperative imaging (90.6 %). Preoperatively,
      benign pseudocysts (BPC) were diagnosed in 84 (36.2 %) patients and intraductal
      papillary mucinous neoplasm (IPMN) in 59 (25.2 %) patients, whereas serous cyst
      adenoma, mucinous cystic neoplasm (MCN), solid pseudopapillary tumors (SPPTs),
      and neuroendocrine tumors (NETs) were less common. In 43 % of patients, the
      preoperative diagnosis concurred with the postoperative diagnosis. The
      preoperative diagnosis was accurate in BPC, less so in IPMN, and inaccurate in
      MCN, NET, and SPPT. However, prediction of tumor biology was accurate; only 11 %
      of the lesions regarded as benign turned out to be malignant after resection, and
      no patient without resection developed malignancy at a median follow-up of 8
      months. Subsequently, 89 % of diagnosed benign tumors had indeed benign
      pathology. CONCLUSIONS: The prediction of biology is often correct, whereas
      specific diagnosis is often wrong. A considerable amount of benign lesions are
      treated more aggressively than warranted if malignancy is suspected prior to
      surgery. Parenchyma-sparing techniques might be an option, but prospective
      multicenter studies need to follow. Experienced pancreatic radiologists can
      improve accuracy of preoperative biology.

PMID- 27048404
TI  - Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin
      alleviates pelvic floor dysfunction.
AB  - BACKGROUND: Pelvic floor dysfunction (PFD) is a group of clinical conditions
      including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The
      abnormality of collagen and elastin metabolism in pelvic connective tissues is
      implicated in SUI and POP. METHODS: To reconstitute the connective tissues with
      normal distribution of collagen and elastin, we transduced elastin to bone marrow
      derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then
      differentiated to fibroblasts using bFGF, which produced collagen and elastin. To
      achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co
      glycolic acid) (PLGA) nanoparticles (NP). RESULTS: In an in vitro cell culture
      system of 7 days, when no additional bFGF was administrated, the initial PLGA
      loaded bFGF NP induced prolonged production of collagen and elastin from elastin
      expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin
      expressing BMSCs into the PFD rats significantly improved the outcome of
      urodynamic tests. Together, these results provided an efficient model of
      connective tissue engineering using BMSC and injectable PLGA-loaded growth
      factors. CONCLUSIONS: Our results provided the first instance of a
      multidisciplinary approach, combining both stem cell and nanoparticle
      technologies, for the treatment of PFD.

PMID- 27048405
TI  - Higher diagnostic accuracy and cost-effectiveness using procalcitonin in the
      treatment of emergency medicine patients with fever (The HiTEMP study): a
      multicenter randomized study.
AB  - BACKGROUND: Fever is a common symptom in the emergency department(ED). Fever can
      be caused by bacterial infections, which are treated with antibiotics. Often,
      bacterial infections cannot be ruled out in the ED using standard diagnostics,
      and empiric antibiotic treatment is started. Procalcitonin(PCT) is a biomarker
      for bacterial infections, but its role in an undifferentiated ED population
      remains unclear. We hypothesize that PCT-guided therapy may reduce antibiotics
      prescription in undifferentiated febrile ED patients. The primary objectives of
      this study are to determine a) the efficacy, b) the safety of PCT-guided therapy,
      and c) the accuracy of the biomarker PCT for bacterial infections. The secondary
      objective is to study the cost-effectiveness of PCT-guided therapy.
      METHODS/DESIGN: This is a multicenter noninferiority randomized controlled trial.
      All adult ED patients with fever(>=38.2  degrees C) are randomized between
      standard care with and without the addition of a PCT level, after written
      informed consent. a) For efficacy, the reduction of patients receiving
      antibiotics is calculated, using a superiority analysis: differences between the
      PCT-guided group and control group are assessed using a Fisher's exact test, and
      a multivariable logistic regression analysis to account for the effects of
      demographic and medical variables on the percentage of febrile patients receiving
      antibiotics. b) Safety consists of a composite endpoint, defined as mortality,
      intensive care admission and ED return visit within 14 days. Noninferiority of
      PCT will be tested using a one-sided 95 % confidence interval for the difference
      in the composite safety endpoint between the PCT-guided and control groups using
      a noninferiority margin of 7.5 %. c) Accuracy of PCT and CRP for the diagnosis of
      bacterial infections will be reported, using the sensitivity, specificity, and
      the area under the receiver-operating-characteristic curve in the definitive
      diagnosis of bacterial infections. The sample size is 550 patients, which was
      calculated using a power analysis for all primary objectives. Enrollment of
      patients started in August 2014 and will last 2 years. DISCUSSION: PCT may offer
      a more tailor-made treatment to the individual ED patient with fever. Prospective
      costs analyses will reveal the economic consequences of implementing PCT-guided
      therapy in the ED. THIS TRIAL IS REGISTERED IN THE DUTCH TRIAL REGISTER: NTR4949.

PMID- 27048406
TI  - Good neurological outcome despite very low regional cerebral oxygen saturation
      during resuscitation--a prospective preclinical trial in 29 patients.
AB  - BACKGROUND: Noninvasive regional cerebral oxygen saturation (rSO2) measurement
      using near-infrared spectroscopy (NIRS) might inform on extent and duration of
      cerebral hypoxia during cardiopulmonary resuscitation (CPR). This information may
      be used to guide resuscitation efforts and may carry relevant early prognostic
      information. METHODS: We prospectively investigated non-traumatic out-of-hospital
      cardiac arrest (OHCA) patients on scene. NIRS was started either during CPR or
      shortly after (<2 min) return of spontaneous circulation (ROSC) by emergency
      medical service (EMS). Outcome was determined at intensive care unit (ICU)
      discharge and 6 months after cardiac arrest. RESULTS: A total of 29 OHCA patients
      were included. In 23 patients NIRS was started during CPR and in 6 patients
      immediately after ROSC. 18 (62.1%) patients did not reach ROSC. Initial rSO2
      during CPR was very low (<50% in all 23 patients, < 30% in 19 of 23 patients)
      with no significant difference between patients achieving ROSC and those who did
      not. Of five patients with ROSC, in whom NIRS was recorded during CPR, two
      reached a good six-months outcome (initial rSO2 22%) and three died during the
      ICU stay (initial rSO2 15, 16 and 46%). In six patients with NIRS started
      immediately after ROSC (<2 min), rSO2 was substantially higher (54-85 %) than in
      patients during CPR (p = 0.006). DISCUSSION AND CONCLUSION: Initial frontal brain
      rSO2 determined by NIRS during CPR was generally very low and recovered rapidly
      after ROSC. Very low initial rSO2 during CPR was compatible with good
      neurological outcome in our limited cohort of patients. Further studies are
      needed to assess in larger cohorts and more detail the implications of very low
      initial rSO2 during CPR on scene.

PMID- 27048407
TI  - A clustering method of Chinese medicine prescriptions based on modified firefly
      algorithm.
AB  - This paper is aimed to study the clustering method for Chinese medicine (CM)
      medical cases. The traditional K-means clustering algorithm had shortcomings such
      as dependence of results on the selection of initial value, trapping in local
      optimum when processing prescriptions form CM medical cases. Therefore, a new
      clustering method based on the collaboration of firefly algorithm and simulated
      annealing algorithm was proposed. This algorithm dynamically determined the
      iteration of firefly algorithm and simulates sampling of annealing algorithm by
      fitness changes, and increased the diversity of swarm through expansion of the
      scope of the sudden jump, thereby effectively avoiding premature problem. The
      results from confirmatory experiments for CM medical cases suggested that,
      comparing with traditional K-means clustering algorithms, this method was greatly
      improved in the individual diversity and the obtained clustering results, the
      computing results from this method had a certain reference value for cluster
      analysis on CM prescriptions.

PMID- 27048408
TI  - Cyclovirobuxinum D alleviates cardiac hypertrophy in hyperthyroid rats by
      preventing apoptosis of cardiac cells and inhibiting the p38 mitogen-activated
      protein kinase signaling pathway.
AB  - OBJECTIVE: To investigate the underlying mechanisms of cyclovirobuxinum D (Cvb-D)
      on alleviating cardiac hypertrophy in rats. METHODS: Sprague-Dawley rats were
      randomly divided into 5 groups: control group; levothyroxine-induced cardiac
      hypertrophy group (model); levothyroxine-induced cardiac hypertrophy + Cvb-D
      group (Cvb-D); levothyroxine-induced cardiac hypertrophy + captopril group
      (captopril); levothyroxine-induced cardiac hypertrophy + SB203580 group
      (SB203580), n=10 for each group. Rats were daily administered the respective
      drugs continuously for14 days by gastric gavage. A rat model of cardiac
      hypertrophy was established by intraperitoneal injection of levothyroxine to
      investigate whether Cvb-D protects against cardiac hypertrophy by inhibiting the
      p38 mitogen-activated protein kinase (MAPK) signaling pathway and preventing
      apoptosis of cardiac cells. RESULTS: Treatment with Cvb-D significantly deceased
      left ventricle hypertrophy, improved the histopathology, hemodynamic conditions,
      and cardiac function in rats with cardiac hypertrophy. Compared with the normal
      control group, in rats with cardiac hypertrophy, expression of bax in the heart
      and phospho-p38 MAPK protein levels were significantly up-regulated (P<0.01 or
      0.05), whereas the bcl-2 protein level was down-regulated (P<0.01). In contrast,
      Cvb-D treatment reversed the changes in bax and phospho-p38 MAPK protein levels
      but increased the bcl-2 protein level (P<0.01 or 0.05), and these effects were
      similar to those of captopril and SB203580 (a specific p38MAPK inhibitor)
      treatment. Furthermore, both Cvb-D, captopril and SB203580 reduced mRNA
      expression of p38alpha, p38beta, c-fos, and c-jun mRNA, and Cvb-D had a stronger
      effect (P<0.01). CONCLUSION: These results demonstrate that Cvb-D protects
      against cardiac hypertrophy, which is possibly mediated by prevention of cardiac
      cell apoptosis and inhibition of the p38MAPK signaling pathway.

PMID- 27048409
TI  - Protective Effects of Danlou Tablet () against Murine Myocardial Ischemia and
      Reperfusion Injury In Vivo.
AB  - OBJECTIVE: To observe the in vivo effect of Danlou Tablet (, DLT) on myocardial
      ischemia and reperfusion (I/R) injury. METHODS: DLT effects were evaluated in
      mouse heart preparation using 30-min coronary occlusion followed by 24-h
      reperfusion and compared among sham group (n=6), I/R group (n=8), IPC group
      (ischemia preconditioning, n=6) and DLT group (I/R with DLT pretreatment for 3
      days, 750 mg*kg-1*day-1, n=8). The effects of DLT were characterized in
      infarction size (IS) compared with risk region (RR) and left ventricle using the
      Evans blue/triphenyltetrazolium chloride double dye staining method in vivo.
      Furthermore, the dose-dependent effect of DLT on I/R injury was evaluated by
      double staining method. Five different concentrations of DLT (0.625, 1.25, 2.5, 5
      and 10 g*kg-1*day-1) were chosen in this study, and dose-response curve of DLT
      was obtained on these data. RESULTS: The ratio of IS to left ventricle was
      significantly smaller in the DLT and IPC groups than the I/R group (P<0.05 or
      P<0.01), the ratio of IS to RR was also reduced in the DLT and IPC groups
      (P<0.01), while there were no differences in RR among the four groups (P>0.05).
      Experiments showed incidence of arrhythmias was reduced in the DLT group
      (P<0.01). Furthermore, DLT produced a dose-dependent inhibitory effect with a
      half maximal inhibitory concentration of 1.225 g*kg-1*day-1. CONCLUSIONS: Our
      research concluded that DLT was effective in reducing I/R injury in mice, and
      provided experimental supports for the clinical use of DLT.

PMID- 27048410
TI  - Acupuncture for moderate to severe allergic rhinitis: A non-randomized controlled
      trial.
AB  - OBJECTIVE: To evaluate the effect and safety of acupuncture therapy on patients
      with moderate to severe allergic rhinitis. METHODS: A non-randomized controlled
      design was used to compare between the acupuncture group and the medication
      group. The acupuncture group received 8-week acupuncture therapy, and the
      medication group received budesonide nasal spray with cetirizine tablets for 8
      weeks. The clinical symptoms and signs were analyzed before treatment, at 4 and 8
      weeks after the start of treatment, and at 12 weeks after the end of treatment.
      Furthermore, the clinical efficacy and safety indicators were compared between
      the two groups. RESULTS: A total of 76 participants consisting of 38 in each of
      the two groups were enrolled. The scores of each clinical symptom and sign,
      including sneezing, runny nose, stuffy nose, nasal itching, and turbinate edema,
      and the total scores decreased over time in both groups (all P<0.05); and no
      difference was found in the scores between the two groups (P>0.05). There was no
      statistically significant difference in the effective rates of the acupuncture
      group at 4 and 8 weeks after the start of treatment as well as at 12-week follow
      up compared with those of the medication group (83.3% vs. 91.2%, and 94.4 % vs.
      85.3%; and 80.6 % vs. 82.4%, all P>0.05). Experimental items including blood
      routine, urine routine, aspartate transaminase, alanine aminotransferase, urea
      nitrogen and creatinine were all in the normal reference ranges during the
      treatment in the acupuncture group. CONCLUSIONS: Acupuncture therapy has a
      comparable effect to the medication treatment on patients with moderate to severe
      allergic rhinitis, and it is safe with no severe adverse effects.

PMID- 27048412
TI  - Giant coronary arterial aneurysm after drug-eluting stent implantation.

PMID- 27048411
TI  - Impact evaluation of CONSORT and STRICTA guidelines on reporting quality for
      randomized controlled trials of acupuncture conducted in China.
AB  - OBJECTIVE: To evaluate and compare the reports' qualities of acupuncture
      randomized controlled trials (RCTs) conducted in China before and after the
      implementation of two guidelines, i.e., the Consolidated Standards of Reporting
      Trials (CONSORT) statement and the Standards for Reporting Interventions in
      Controlled Trials of Acupuncture (STRICTA). METHODS: Proportions of studies that
      reported CONSORT and STRICTA items were compared for the years before and after
      implementation of these two guidelines. In addition, the total score of each
      item's reporting were calculated and reported differences during different date
      ranges were compared. RESULTS: For CONSORT items (maximum score 8), there was
      evidence of a slight improvement in reporting between 1994-1995 and 1999-2000
      combined (2.5+/-0.6) and 2004-2005 and 2009-2010 combined (3.0+/-0.9; difference
      0.4, 95% confidence interval, 0.3 to 0.6, P<0.01). For STRICTA items (maximum
      score 17), there was evidence that a slight improvement in reporting between 1994
      1995 and 1999-2000 combined (8.6+/-2.1) and 2004-2005 and 2009-2010 combined
      (10.1+/-1.8; difference 1.5, 95% confidence interval, 1.1 to 1.9, P<0.01).
      CONCLUSION: Quality of reporting for RCTs of acupuncture treatment conducted in
      China have generally improved since the introduction of the STRICTA and CONSORT
      guidelines.

PMID- 27048413
TI  - Distinctive impact of pre-existing interstitial lung disease on the risk of
      chemotherapy-related lung injury in patients with lung cancer.
AB  - PURPOSE: Pre-existing interstitial lung disease (pre-ILD) increases the risk of
      chemotherapy-related lung injury (CRLI). However, whether the risk varies by type
      of anti-cancer cytotoxic agent in patients with pre-ILD is unknown. In this
      study, we hypothesized that S-1, an oral fluoropyrimidine agent, is associated
      with a smaller CRLI risk than docetaxel (DTX) and investigated these agents
      together with radiological evaluations of pre-ILD via pre-treatment chest
      computed tomography (CT). METHODS: After reviewing 234 and 352 patients who
      underwent evaluable chest CT within 6 months prior to the administration of S-1
      or DTX, respectively, from January 2006 to October 2014, 60 and 89, respectively,
      of these patients with pre-ILD were retrospectively analysed. RESULTS: In total,
      2 persons administered S-1 (3 %) and 16 treated with DTX (18 %) developed CRLI (p
      = 0.007) after the initial treatment (mean, 61 days), of whom 1 and 7,
      respectively, died because of respiratory failure. Pre-treatment CT revealed that
      9 S-1-treated patients (16 %) and 15 DTX-treated patients (17 %) had pre-ILD
      occupying more than 25 % of the lung field. Multivariate analysis demonstrated
      that DTX administration increased the risk of CRLI by 6.47-fold versus S-1
      therapy (p = 0.016). Of note, the area occupied by pre-ILD was also associated
      with the risk of CRLI (<25 %; odds ratio 0.309, p = 0.045). CONCLUSIONS: Our
      results indicated that S-1 is associated with a smaller risk of CRLI than DTX.
      The area occupied by pre-ILD should also be noted when administrating anti-cancer
      agents.

PMID- 27048414
TI  - Salivary agglutinin is the major component in human saliva that modulates the
      lectin pathway of the complement system.
AB  - Saliva interacts with blood after mucosal damage or leakage of gingival
      crevicular fluid. Surface-adsorbed salivary agglutinin (SAG) activates the lectin
      pathway (LP) of the complement system via mannose-binding lectin, while SAG in
      solution inhibits complement activation. In the present study we investigated if,
      next to SAG, whole and glandular saliva itself and other salivary glycoproteins
      activate or inhibit the LP. Complement activation was measured by detecting C4
      deposition on microtiter plates coated with saliva or purified proteins.
      Complement inhibition was measured after incubating serum with saliva or proteins
      in microtiter plates coated with mannan, an LP activator. Adsorbed whole,
      sublingual and submandibular saliva showed LP-dependent complement activation.
      Blood group secretors, but not non-secretors, activated the LP. Saliva of both
      secretors and non-secretors inhibited C4 deposition on mannan. After depletion of
      SAG, saliva no longer inhibited the LP. Other salivary proteins, including
      amylase, MUC5B and histatin 2, did not activate or inhibit the LP. Surface
      adsorbed whole saliva and glandular saliva samples activate the LP of complement,
      depending on the presence of SAG and the secretor status of the donor. In
      solution, saliva inhibits the LP, depending on the presence of SAG, but
      independent of the secretor status.

PMID- 27048415
TI  - Dietary flaxseed oil and fish oil ameliorates renal oxidative stress, protein
      glycation, and inflammation in streptozotocin-nicotinamide-induced diabetic rats.
AB  - Protective and prophylactic effects of omega-3 fatty acids on oxidative stress
      and inflammation are well known. We assessed beneficial effects of flaxseed oil
      and fish oil on streptozotocin (65 mg/kg; i.p.)-nicotinamide (110 mg/kg; i.p.)
      induced diabetic rats by studying renal expression of antioxidant and
      inflammatory genes. Diabetic rats given 10 % flaxseed oil or 10 % fish oil diet
      for 35 days showed significant decrease in renal lipid peroxidation. Flaxseed oil
      diet resulted in up-regulation of renal superoxide dismutase-1 (SOD-1) (activity
      and expression) and glutathione peroxidase-1 (GPx-1) expression. Furthermore,
      both diets up-regulated catalase (CAT) (activity and expression) and down
      regulated heme oxygenase-1 (HO-1) expression. Both diets were able to limit the
      renal advanced glycation end products (AGEs) formation and reduced receptor of
      AGE (RAGE) protein expression significantly. Expressions of interleukin-6 (IL-6)
      and NF-kappaB p65 subunit were down-regulated significantly by flaxseed oil or
      fish oil diet. The histological tubular injuries were also lowered by both diets.
      These results suggest that dietary omega-3 fatty acids may slow the progression
      of diabetic nephropathy (DN) associated with oxidative stress, glycation, and
      inflammation in the kidney. 

PMID- 27048416
TI  - Spread of Coxiella burnetii between dairy cattle herds in an enzootic region:
      modelling contributions of airborne transmission and trade.
AB  - Q fever, a worldwide zoonotic disease caused by Coxiella burnetii, is a looming
      concern for livestock and public health. Epidemiological features of inter-herd
      transmission of C. burnetii in cattle herds by wind and trade of cows are poorly
      understood. We present a novel dynamic spatial model describing the inter-herd
      regional spread of C. burnetii in dairy cattle herds, quantifying the ability of
      airborne transmission and animal trade in C. burnetii propagation in an enzootic
      region. Among all the new herd infections, 92% were attributed to airborne
      transmission and the rest to cattle trade. Infections acquired following airborne
      transmission were shown to cause relatively small and ephemeral intra-herd
      outbreaks. On the contrary, disease-free herds purchasing an infectious cow
      experienced significantly higher intra-herd prevalence. The results also
      indicated that, for short duration, both transmission routes were independent
      from each other without any synergistic effect. The model outputs applied to the
      Finistere department in western France showed satisfactory sensitivity (0.71) and
      specificity (0.80) in predicting herd infection statuses at the end of one year
      in a neighbourhood of 3 km around expected incident herds, when compared with
      data. The model developed here thus provides important insights into the spread
      of C. burnetii between dairy cattle herds and paves the way for implementation
      and assessment of control strategies.

PMID- 27048417
TI  - Distinct breast cancer characteristics between screen- and self-detected breast
      cancers recorded in the Japanese Breast Cancer Registry.
AB  - The rate of breast cancer screening for women of all ages in Japan is increasing.
      However, little is known about the biological differences between screen- and
      self-detected tumors. We used data from the Japanese Breast Cancer Registry
      (JBCR), a nationwide registry of newly diagnosed breast cancer cases in Japan, to
      investigate patients diagnosed between January 1, 2004 and December 31, 2011. We
      compared the clinicopathological features of tumors and assessed yearly trends
      regarding the proportion of screen-detected cases during the study period. We
      found that 31.8 % (65,358/205,544) of cancers were detected by screening.
      Asymptomatic tumors detected by screening (asymptomatic) were more likely to have
      favorable prognostic features than those that were self-detected (ductal
      carcinoma in situ [DCIS]: 19.8 versus 4.1 %, node-negative: 77.0 versus 61.6 %,
      and estrogen receptor-positive [ER+]: 82.0 versus 72.9 %, respectively). All
      these findings were statistically significant (p < .001). The proportion of
      breast cancers detected by screening among all cases increased from 21.7 % in
      2004 to 37.1 % in 2011. During the same time period, the proportion of screen
      detected DCIS increased from 41.5 to 66.0 % and that of ER+ cancers increased
      from 23.2 to 39.7 %. This study demonstrated that low-risk tumors, including
      DCIS, ER+, and lower TNM stage, account for a substantial proportion of clinical
      screening-detected cancers. The differences in biological characteristics between
      screen- and self-detected cancers may account in part for the limited efficacy of
      breast cancer screening programs aimed at improving breast cancer mortality.

PMID- 27048418
TI  - Discrepancies in Adolescents' and Mothers' Perceptions of the Family and Mothers'
      Psychological Symptomatology.
AB  - Research has shown that discrepancies in adolescents' and their parents'
      perceptions of the family are linked to adolescent adjustment. Of note, the
      majority of studies to date have focused on differences in perceptions between
      adolescents and their parents. However, recent research has suggested that
      convergence in adolescents' and their parents' perceptions of the family may be
      linked to adolescent psychological outcomes as well. To date, research examining
      adolescents' and parents' perceptions of the family in relation to outcomes has
      focused only on adolescent outcomes. Therefore, the goal of this study was to
      examine the relationship between adolescents' and their mothers' perceptions of
      the family and mothers' psychological symptomatology. Surveys were administered
      to 141 adolescents (56 % girls) and their mothers during the spring of 2007. The
      results indicated that adolescents viewed the family more negatively in
      comparison to their mothers. In addition, interactions between adolescents' and
      mothers' reports of open communication, communication problems, and family
      satisfaction predicted mothers' psychological symptoms. These interactions
      indicated that mothers reported the most psychological symptoms when adolescents
      and mothers agreed that family functioning was poor (e.g., low open
      communication, high communication problems, low family satisfaction). The
      findings from this study underscore the need to consider adolescents' and
      parents' perceptions of the family in tandem when considering parental
      psychological adjustment.

PMID- 27048419
TI  - Structural Characterization of Missense Mutations Using High Resolution Mass
      Spectrometry: A Case Study of the Parkinson's-Related Protein, DJ-1.
AB  - Missense mutations that lead to the expression of mutant proteins carrying single
      amino acid substitutions are the cause of numerous diseases. Unlike gene lesions,
      insertions, deletions, nonsense mutations, or modified RNA splicing, which affect
      the length of a polypeptide, or determine whether a polypeptide is translated at
      all, missense mutations exert more subtle effects on protein structure, which are
      often difficult to evaluate. Here, we took advantage of the spectral resolution
      afforded by the EMR Orbitrap platform, to generate a mass spectrometry-based
      approach relying on simultaneous measurements of the wild-type protein and the
      missense variants. This approach not only considerably shortens the analysis time
      due to the concurrent acquisition but, more importantly, enables direct
      comparisons between the wild-type protein and the variants, allowing
      identification of even subtle structural changes. We demonstrate our approach
      using the Parkinson's-associated protein, DJ-1. Together with the wild-type
      protein, we examined two missense mutants, DJ-1A104T and DJ-1D149A, which lead to
      early-onset familial Parkinson's disease. Gas-phase, thermal, and chemical
      stability assays indicate clear alterations in the conformational stability of
      the two mutants: the structural stability of DJ-1D149A is reduced, whereas that
      of DJ-1A104T is enhanced. Overall, we anticipate that the methodology presented
      here will be applicable to numerous other missense mutants, promoting the
      structural investigations of multiple variants of the same protein. Graphical
      Abstract ?.

PMID- 27048420
TI  - Pulmonary vein reconnection and arrhythmia progression after antral linear
      catheter ablation of paroxysmal and persistent atrial fibrillation.
AB  - BACKGROUND: Assumption of different substrates is the basis for different
      ablation strategies in patients with paroxysmal and persistent atrial
      fibrillation (AF). We aimed to investigate pulmonary vein reconnection and
      influence on progression of initial paroxysmal (pAF) versus persistent atrial
      fibrillation (perAF). METHODS: Between January 2010 and November 2012, 149
      patients (117 men, mean age 59 +/- 11 years, range 27-80 years) underwent at
      least one redo antral pulmonary vein isolation (PVI) using NavX-guided irrigated
      tip radiofrequency catheter ablation. We analyzed whether and where reconnection
      of pulmonary veins was detected, and whether there were differences between
      patients with pAF and perAF. RESULTS: Of the 149 patients who underwent a redo
      antral PVI, 80 patients had pAF and 69 had perAF. One, two and three redo PVIs
      were performed in 149, 26 and 6 patients, respectively. Reconnection of at least
      one PV was detected in all patients at the second PVI, in 19 of 26 patients (73
      %) at the third PVI and 5 of 6 patients (83 %) at the fourth PVI. 20 (29 %)
      patients with perAF prior to the first PVI had pAF at the second PVI, whereas 15
      (19 %) patients with initial pAF had persistent AF at the time of the first redo
      procedure. From the second to the third PVI, four patients had developed perAF
      after previous pAF and two with per AF now had pAF. PV reconnection was observed
      independent of underlying AF type. At the second redo procedure, of those with
      reconnected veins 12 had pAF and 13 perAF. At the third redo procedure, four
      patients had pAF and four perAF. CONCLUSION: Most patients with recurrent AF
      after PVI showed at least one reconnected vein during redo procedures.
      Reconnection was identified irrespective of the underlying AF type. Progression
      from pAF to perAF and vice versa was observed irrespective of the initial AF
      type.

PMID- 27048423
TI  - Legal Standards for Brain Death and Undue Influence in Euthanasia Laws.
AB  - A major appellate court decision from the United States seriously questions the
      legal sufficiency of prevailing medical criteria for the determination of death
      by neurological criteria. There may be a mismatch between legal and medical
      standards for brain death, requiring the amendment of either or both. In South
      Australia, a Bill seeks to establish a legal right for a defined category of
      persons suffering unbearably to request voluntary euthanasia. However, an
      essential criterion of a voluntary decision is that it is not tainted by undue
      influence, and this Bill falls short of providing adequate guidance to assess for
      undue influence. 

PMID- 27048421
TI  - Communicating statin evidence to support shared decision-making.
AB  - BACKGROUND: The practice of clinical medicine rests on a foundation of ethical
      principles as well as scientific knowledge. Clinicians must artfully balance the
      principle of beneficence, doing what is best for patients, with autonomy,
      allowing patients to make their own well-informed health care decisions. The
      clinical communication process is complicated by varying degrees of confidence in
      scientific evidence regarding patient-oriented benefits, and by the fact that
      most medical options are associated with possible harms as well as potential
      benefits. DISCUSSION: Evidence-based clinical guidelines often neglect patient
      oriented issues involved with the thoughtful practice of shared decision-making,
      where individual values, goals, and preferences should be prioritized. Guidelines
      on the use of statin medications for preventing cardiovascular events are a case
      in point. Current guidelines endorse the use of statins for people whose 10-year
      risk of cardiovascular events is as low as 7.5%. Previous guidelines set the 10
      year risk benchmark at 20%. Meta-analysis of randomized trials suggests that
      statins can reduce cardiovascular event rates by about 25%, bringing 10-year risk
      from 7.5 to 5.6%, for example, or from 20 to 15%. Whether or not these benefits
      should justify the use of statins for individual patients depends on how those
      advantages are valued in comparison with disadvantages, such as side effect
      risks, and with inconveniences associated with taking a pill each day and
      visiting clinicians and laboratories regularly. CONCLUSIONS: Whether or not the
      overall benefit-harm balance justifies the use of a medication for an individual
      patient cannot be determined by a guidelines committee, a health care system, or
      even the attending physician. Instead, it is the individual patient who has a
      fundamental right to decide whether or not taking a drug is worthwhile.
      Researchers and professional organizations should endeavor to develop shared
      decision-making tools that provide up-to-date best evidence in easily
      understandable formats, so as to assist clinicians in helping their patients to
      make the decisions that are right for them.

PMID- 27048424
TI  - US medical schools protest against subpoenas requesting names of fetal
      researchers.

PMID- 27048425
TI  - Generation of Transgenic Porcine Fibroblast Cell Lines Using Nanomagnetic Gene
      Delivery Vectors.
AB  - The transgenic process allows for obtaining genetically modified animals for
      divers biomedical applications. A number of transgenic animals for
      xenotransplantation have been generated with the somatic cell nuclear transfer
      (SCNT) method. Thereby, efficient nucleic acid delivery to donor cells such as
      fibroblasts is of particular importance. The objective of this study was to
      establish stable transgene expressing porcine fetal fibroblast cell lines using
      magnetic nanoparticle-based gene delivery vectors under a gradient magnetic
      field. Magnetic transfection complexes prepared by self-assembly of suitable
      magnetic nanoparticles, plasmid DNA, and an enhancer under an inhomogeneous
      magnetic field enabled the rapid and efficient delivery of a gene construct
      (pCD59-GFPBsd) into porcine fetal fibroblasts. The applied vector dose was
      magnetically sedimented on the cell surface within 30 min as visualized by
      fluorescence microscopy. The PCR and RT-PCR analysis confirmed not only the
      presence but also the expression of transgene in all magnetofected transgenic
      fibroblast cell lines which survived antibiotic selection. The cells were
      characterized by high survival rates and proliferative activities as well as
      correct chromosome number. The developed nanomagnetic gene delivery formulation
      proved to be an effective tool for the production of genetically engineered
      fibroblasts and may be used in future in SCNT techniques for breeding new
      transgenic animals for the purpose of xenotransplantation. 

PMID- 27048426
TI  - A longitudinal study of mental health symptoms in young prisoners: exploring the
      influence of personal factors and the correctional climate.
AB  - BACKGROUND: Despite the high prevalence rate of mental health problems among
      young prisoners, little is known about the longitudinal course and covariates of
      their mental health symptoms during incarceration, especially the influence of
      the correctional climate. The current study aimed: (1) to examine changes in
      young prisoners' mental health symptoms during incarceration, (2) to identify
      personal factors associated with their mental health symptoms and perceptions of
      the correctional climate, and (3) to test the incremental effect of perceptions
      of the correctional climate on mental health symptoms. METHODS: Data were
      obtained from a sample of 75 youths (aged 17 to 22 years) detained in a
      Portuguese young offender prison. Data were gathered 1, 3, and 6 months after
      their admission in this facility. Socio-demographic, clinical and criminological
      variables were collected. Mental health symptoms and perceptions of the
      correctional climate were assessed through self-report assessment tools. Linear
      and logistic (multi-level) regressions and tests for differences between means
      were performed to analyze the data. RESULTS: Overall, mental health symptoms
      marginally declined by the sixth month in prison. Prisoners with a history of
      mental health treatment were more likely to have increased symptoms. Higher
      levels of mental health symptoms were associated with a history of mental health
      treatment, remand status, and a lower educational level. Better perceptions of
      the correctional climate were associated with Black race and participation in
      prison activities. A negative perception of the correctional climate was the
      strongest covariate of young prisoners' mental health symptoms and had
      incremental validity over that of personal variables. CONCLUSIONS: The results
      highlight that both characteristics of the prisoners and of the prison
      environment influence young prisoners' mental health. Prison management can try
      to reduce young prisoners' mental health problems by developing scientific
      procedures for their mental health assessment and creating a more beneficial
      correctional climate.

PMID- 27048429
TI  - Eye Movement Desensitization Reprocessing as Treatment for Chronic Pain
      Syndromes: A Literature Review.
AB  - BACKGROUND: Chronic pain is public health problem in the United States, costing
      upwards of $560 to $635 billion annually. Guidelines consistently recommend
      psychological treatment for chronic pain. Eye movement desensitization
      reprocessing (EMDR) psychotherapy may provide an alternate approach to treating
      chronic pain. OBJECTIVE: Review of literature to evaluate the effectiveness of
      EMDR in the treatment of chronic pain. METHOD: A literature search of seven
      databases was conducted to find relevant studies addressing the use of EMDR for
      chronic pain. RESULTS: Most studies reported improvement in pain and
      psychological indices with EMDR. CONCLUSIONS: Because most literature reported
      case studies, the results have limited generalizability. However, for clients who
      suffer from chronic pain, EMDR is a reasonable treatment alternative.

PMID- 27048428
TI  - Production of small RNAs by mammalian Dicer.
AB  - MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for
      the biogenesis of small RNAs guiding post-transcriptional repression.
      Requirements for Dicer activity differ in the two pathways. The biogenesis of
      miRNAs requires a single Dicer cleavage of a short hairpin precursor to produce a
      small RNA with a precisely defined sequence, while small RNAs in RNAi come from a
      processive cleavage of a long double-stranded RNA (dsRNA) into a pool of small
      RNAs with different sequences. While Dicer is generally conserved among
      eukaryotes, its substrate recognition, cleavage, and biological roles differ. In
      Metazoa, a single Dicer can function as a universal factor for RNAi and miRNA
      pathways or as a factor adapted specifically for one of the pathways. In this
      review, we focus on the structure, function, and evolution of mammalian Dicer. We
      discuss key structural features of Dicer and other factors defining Dicer
      substrate repertoire and biological functions in mammals in comparison with
      invertebrate models. The key for adaptation of Dicer for miRNA or RNAi pathways
      is the N-terminal helicase, a dynamically evolving Dicer domain. Its
      functionality differs between mammals and invertebrates: the mammalian Dicer is
      well adapted to produce miRNAs while its ability to support RNAi is limited.

PMID- 27048427
TI  - Subgenual Cingulum Microstructure Supports Control of Emotional Conflict.
AB  - Major depressive disorder (MDD) is associated with specific difficulties in
      attentional disengagement from negatively valenced material. Diffusion MRI
      studies have demonstrated altered white matter microstructure in the subgenual
      cingulum bundle (CB) in individuals with MDD, though the functional significance
      of these alterations has not been examined formally. This study explored whether
      individual differences in selective attention to negatively valenced stimuli are
      related to interindividual differences in subgenual CB microstructure. Forty-six
      individuals (21 with remitted MDD, 25 never depressed) completed an emotional
      Stroop task, using happy and angry distractor faces overlaid by pleasant or
      unpleasant target words and a control gender-based Stroop task. CBs were
      reconstructed in 38 individuals using diffusion-weighted imaging and
      tractography, and mean fractional anisotropy (FA) computed for the subgenual,
      retrosplenial, and parahippocampal subdivisions. No significant correlations were
      found between FA and performance in the control gender-based Stroop task in any
      CB region. However, the degree of interference produced by angry face distractors
      on time to identify pleasant words (emotional conflict) correlated selectively
      with FA in the subgenual CB (r = -0.53; P = 0.01). Higher FA was associated with
      reduced interference, irrespective of a diagnosis of MDD, suggesting that
      subgenual CB microstructure is functionally relevant for regulating attentional
      bias toward negative interpersonal stimuli.

PMID- 27048430
TI  - Optimal vaccination strategies and rational behaviour in seasonal epidemics.
AB  - We consider a SIRS model with time dependent transmission rate. We assume time
      dependent vaccination which confers the same immunity as natural infection. We
      study two types of vaccination strategies: (i) optimal vaccination, in the sense
      that it minimizes the effort of vaccination in the set of vaccination strategies
      for which, for any sufficiently small perturbation of the disease free state, the
      number of infectious individuals is monotonically decreasing; (ii) Nash
      equilibria strategies where all individuals simultaneously minimize the joint
      risk of vaccination versus the risk of the disease. The former case corresponds
      to an optimal solution for mandatory vaccinations, while the second corresponds
      to the equilibrium to be expected if vaccination is fully voluntary. We are able
      to show the existence of both optimal and Nash strategies in a general setting.
      In general, these strategies will not be functions but Radon measures. For
      specific forms of the transmission rate, we provide explicit formulas for the
      optimal and the Nash vaccination strategies.

PMID- 27048431
TI  - Assessment of myocardial function in preterm infants with chronic lung disease
      using tissue Doppler imaging.
AB  - OBJECTIVES: To assess myocardial function and presence of pulmonary hypertension
      (PH) using both tissue Doppler imaging (TDI) and conventional echocardiography in
      preterm infants of <32 weeks gestation with chronic lung disease (CLD). DESIGN:
      Prospective observational study. SETTING: Tertiary neonatal intensive care unit.
      PATIENTS: Three groups of preterm infants were recruited. Group 1-CLD receiving
      positive pressure airway support including high-flow humidified nasal cannula
      oxygen (n=25), group 2-CLD receiving low-flow nasal oxygen (n=25) and group 3-no
      CLD (n=22). METHODS: Echocardiography was performed around 36 weeks corrected
      gestational age. Myocardial function and PH were assessed using both conventional
      (left ventricular fractional shortening (LVFS) and left ventricular output (LVO),
      tricuspid regurgitation and ventricular septal flattening) and TDI techniques
      (myocardial velocities, myocardial performance index (MPI) and right ventricular
      isovolumetric relaxation time (RV-IVRT)). RESULTS: The MPI of right ventricle
      (RV) and left ventricle (LV) was significantly higher in CLD infants: mean RV MPI
      group 1-0.79, group 2-0.65 and group3-0.52. LV MPI: group 1-0.77, group 2-0.70
      and group 3-0.45. There was a trend towards higher MPIs in group 1 compared with
      group 2. LVFS and LVO were similar across all three groups. RV-IVRT was also
      significantly higher in infants with CLD infants (group 1-64 milliseconds, group
      2-62 milliseconds and group 3-52 milliseconds). PH was not detected by
      conventional echocardiography. CONCLUSIONS: Infants with CLD have evidence of
      relative biventricular dysfunction and higher pulmonary arterial blood pressure
      as demonstrated by TDI, which were not detected by conventional echocardiography.

PMID- 27048432
TI  - The relation between splanchnic ischaemia and intestinal damage in necrotising
      enterocolitis.
AB  - OBJECTIVES: The underlying pathophysiology of necrotising enterocolitis (NEC)
      remains incompletely understood, particularly the role of intestinal perfusion.
      We aimed to determine the relation between cerebral and splanchnic fractional
      tissue oxygen extraction (FTOE), a marker for tissue underperfusion, with
      intestinal fatty acid-binding protein in plasma (I-FABPp), a marker for
      intestinal damage, in infants with NEC. Furthermore, we investigated the combined
      courses of cerebral and splanchnic FTOE values and I-FABPp levels in
      uncomplicated (conservative treatment) and complicated NEC (surgery or death).
      DESIGN: This study was part of a prospective observational cohort study.
      PATIENTS: We included 19 preterm infants with NEC (9 uncomplicated, 10
      complicated). INTERVENTIONS: Using near-infrared spectroscopy, we measured
      regional cerebral and splanchnic tissue oxygen saturations continuously for 48 h
      after NEC onset. We measured I-FABPp levels simultaneously. MAIN OUTCOME
      MEASURES: We used Spearman correlation tests to calculate correlation
      coefficients between FTOE values and I-FABPp levels in uncomplicated and
      complicated NEC. RESULTS: Median (range) gestational age was 28 (25-36) weeks and
      median (range) birth weight was 1290 (740-2400) g. Cerebral and splanchnic FTOE
      values correlated strongly with I-FABPp levels (rho between .745 and 0.900;
      p<0.001-0.037) during the first 16 h after NEC onset. Thereafter, in
      uncomplicated NEC, splanchnic FTOE values increased while I-FABPp levels
      decreased concomitantly. In complicated NEC both splanchnic FTOE values and I
      FABPp levels decreased. CONCLUSIONS: Combining cerebral and splanchnic FTOE
      values with I-FABPp levels, gives insight in the pathological chain of events
      resulting in progression or recovery of intestinal ischaemia in NEC. TRIAL
      REGISTRATION NUMBER: NTR3239.

PMID- 27048433
TI  - Smokeless tobacco use in Sweden and other 17 European countries.
AB  - INTRODUCTION: The purpose of this study is to report prevalence and determinants
      of use of smokeless tobacco in a representative sample of men and women from
      Sweden, where Swedish snus sales are legal, and from 17 other European countries,
      where sales of smokeless tobacco are restricted. METHODS: In 2010, a face-to-face
      survey including information on current smokeless tobacco use was conducted in a
      representative sample of around 1000 individuals aged >=15 years per country in
      Albania, Austria, Bulgaria, Czech Republic, Croatia, England, Finland, France,
      Greece, Hungary, Ireland, Italy, Latvia, Poland, Portugal, Romania, Spain and
      Sweden. RESULTS: In Sweden, the overall prevalence of smokeless tobacco use was
      12.3% (20.7% in men, 3.5% in women). The corresponding estimate for other
      European countries combined was 1.1% (1.2% in men, 1.1% in women). Compared with
      never smokers, former smokers in Sweden were significantly more likely to use
      smokeless tobacco (odds ratio, OR: 2.67), whereas no difference in use was
      observed in other countries (OR: 1.04). Use of smokeless tobacco was similar
      among current smokers in Sweden (OR: 1.96) and in other countries (OR: 2.40) when
      contrasted to never smokers. In Sweden there were no differences in the number of
      cigarettes/day between smokers who also use smokeless tobacco (13.3
      cigarettes/day) and exclusive cigarette smokers (12.9 cigarettes/day; P = 0.785).
      CONCLUSIONS: Excluding Sweden, current oral tobacco use was not commonly reported
      in the European countries surveyed and was similarly rare both in men and in
      women. In Sweden, however, use of smokeless tobacco was about 10-fold higher than
      the rest of Europe and more prevalent in men than in women.

PMID- 27048434
TI  - It Takes More than a Village: Building a Network of Safety in Nepal's Mountain
      Communities.
AB  - Purpose This report from the field details the ways that one small maternal child
      health NGO, which began its work in Tibet and now works in the mountain
      communities of Nepal, has established a model for integrated healthcare delivery
      and support it calls the "network of safety." Description It discusses some of
      the challenges faced both by the NGO and by the rural mountain communities with
      whom it partners, as well as with the government of Nepal. Conclusion This report
      describes and analyzes successful efforts to reduce maternal and infant mortality
      in a culturally astute, durable, and integrated way, as well as examples of
      innovation and success experienced by enacting the network of safety model.

PMID- 27048435
TI  - Presenting symptoms predict local staging of anal cancer: a retrospective
      analysis of 86 patients.
AB  - BACKGROUND: Incidence of anal carcinoma (AC) is increasing and timely diagnosis
      is critical for efficient therapy. However, there is a paucity of recent studies
      addressing clinical symptoms and physical findings of anal carcinoma. METHODS: We
      performed a retrospective study reviewing history, symptoms and physical findings
      from 86 patients with newly diagnosed AC. We analyzed frequency of symptoms and
      physical findings according to T and TNM stage and their predictive value
      regarding tumor stage. RESULTS: Most patients presented with T2 (37 %) or T3 (29
      %) cancer. 85 of 86 patients were symptomatic with anal bleeding (78 %),
      anal/perianal pain (63 %), weight loss (31 %) and foreign body sensation (22 %).
      95 % of patients had >=1 finding on physical examination including a visible
      tumor, palpable resistance and pain/blood during digital rectal examination.
      Patients with locally advanced disease (T3/T4) presented with more symptoms (p <
      0.01) and more physical findings (p = 0.04) than patients with T1/T2 disease. On
      multivariate regression analysis perianal pain, painful defecation and weight
      loss were significantly associated with T3/T4 disease. CONCLUSION: Clinical
      symptoms and physical findings are present in nearly all AC patients. Pain
      referred to the perianal region, painful defecation and weight loss have
      predictive value for locally advanced disease.

PMID- 27048436
TI  - Reviewing the literature, how systematic is systematic?
AB  - Introduction Professor Archibald Cochrane, after whom the Cochrane Collaboration
      is named, was influential in promoting evidence-based clinical practice. He
      called for "relevant, valid research" to underpin all aspects of healthcare.
      Systematic reviews of the literature are regarded as a high quality source of
      cumulative evidence but it is unclear how truly systematic they, or other review
      articles, are or 'how systematic is systematic?' Today's evidence-based review
      industry is a burgeoning mix of specialist terminology, collaborations and
      foundations, databases, portals, handbooks, tools, criteria and training courses.
      Aim of the review This study aims to identify uses and types of reviews, key
      issues in planning, conducting, reporting and critiquing reviews, and factors
      which limit claims to be systematic. Method A rapid review of review articles
      published in IJCP. Results This rapid review identified 17 review articles
      published in IJCP between 2010 and 2015 inclusive. It explored the use of
      different types of review article, the variation and widely available range of
      guidelines, checklists and criteria which, through systematic application, aim to
      promote best practice. It also identified common pitfalls in endeavouring to
      conduct reviews of the literature systematically. Discussion Although a limited
      set of IJCP reviews were identified, there is clear evidence of the variation in
      adoption and application of systematic methods. The burgeoning evidence industry
      offers the tools and guidelines required to conduct systematic reviews, and other
      types of review, systematically. This rapid review was limited to the database of
      one journal over a period of 6 years. Although this review was conducted
      systematically, it is not presented as a systematic review. Conclusion As a
      research community we have yet to fully engage with readily available guidelines
      and tools which would help to avoid the common pitfalls. Therefore the question
      remains, of not just IJCP but potentially all published reviews, 'how systematic
      is systematic?' 

PMID- 27048437
TI  - Effect of Vagal Nerve Blockade on Moderate Obesity with an Obesity-Related
      Comorbid Condition: the ReCharge Study.
AB  - BACKGROUND: Vagal nerve blockade (vBloc) therapy was shown to be a safe and
      effective treatment for moderate to severe obesity. This report summarizes the
      safety and efficacy of vBloc therapy in the prespecified subgroup of patients
      with moderate obesity. METHODS: The ReCharge Trial is a double-blind, randomized
      controlled clinical trial of participants with body mass index (BMI) of 40-45 or
      35-40 kg/m(2) with at least one obesity-related comorbid condition. Participants
      were randomized 2:1 to implantation with either a vBloc or sham device with
      weight management counseling. Eighty-four subjects had moderate obesity (BMI 35
      40 kg/m(2)) at randomization. RESULTS: Fifty-three participants were randomized
      to vBloc and 31 to sham. Qualifying obesity-related comorbidities included
      dyslipidemia (73%), hypertension (58%), sleep apnea (33%), and type 2 diabetes
      (8%). The vBloc group achieved a percentage excess weight loss (%EWL) of 33% (11%
      total weight loss (%TWL)) compared to 19% EWL (6% TWL) with sham at 12 months
      (treatment difference 14 percentage points, 95% CI, 7-22; p < 0.0001). Common
      adverse events of vBloc through 12 months were heartburn/dyspepsia and implant
      site pain; the majority of events were reported as mild or moderate. CONCLUSIONS:
      vBloc therapy resulted in significantly greater weight loss than the sham control
      among participants with moderate obesity and comorbidities with a well-tolerated
      safety profile.

PMID- 27048438
TI  - Letter to "Pharmacotherapy in conjunction with diet and exercise program for the
      treatment of weight recidivism or weight loss plateau post-bariatric surgery: a
      retrospective review".

PMID- 27048439
TI  - Weight Regain Following Sleeve Gastrectomy-a Systematic Review.
AB  - Sleeve gastrectomy (SG) is a commonly performed bariatric procedure. Weight
      regain following SG is a significant issue. Yet the defining, reporting and
      understanding of this phenomenon remains largely neglected. Systematic review was
      performed to locate articles reporting the definition, rate and/or cause of
      weight regain in patients at least 2 years post-SG. A range of definitions
      employed to describe weight regain were identified in the literature. Rates of
      regain ranged from 5.7 % at 2 years to 75.6 % at 6 years. Proposed causes of
      weight regain included initial sleeve size, sleeve dilation, increased ghrelin
      levels, inadequate follow-up support and maladaptive lifestyle behaviours.
      Bariatric literature would benefit from standardising definitions used to report
      weight regain and its rate in clinical series. Larger prospective studies are
      required to further understand mechanisms of weight regain following SG.

PMID- 27048440
TI  - The power of stories in Pediatrics and Genetics.
AB  - On the occasion of the opening ceremony of the 43rd Sicilian Congress of
      Pediatrics, linked with Italian Society of Pediatrics SIP, SIN, SIMEUP, SIAIP and
      SINP, held in Catania in November 2015, the Organizing Committee dedicated a
      tribute to Professor John Opitz and invited him to give a Masters Lecture for the
      attendees at the Congress. The theme expounded was "Storytelling in Pediatrics
      and Genetics: Lessons from Aesop and from Mendel". The contribution of John Opitz
      to the understanding of pediatric clinical disorders and genetic anomalies has
      been extremely relevant. The interests of Professor John Opitz are linked not
      only to genetic disorders but also extend to historical medicine, history of the
      literature and to human evolution. Due to his exceptional talent, combined with
      his specific interest and basal knowledge in the genetic and pediatric fields, he
      is widely credited to be one of the best pediatricians in the world.

PMID- 27048441
TI  - Enhanced spatial resolution on figures versus grounds.
AB  - Much is known about the cues that determine figure-ground assignment, but less is
      known about the consequences of figure-ground assignment on later visual
      processing. Previous work has demonstrated that regions assigned figural status
      are subjectively more shape-like and salient than background regions. The
      increase in subjective salience of figural regions could be caused by a number of
      processes, one of which may be enhanced perceptual processing (e.g., an enhanced
      neural representation) of figures relative to grounds. We explored this
      hypothesis by having observers perform a perceptually demanding spatial
      resolution task in which targets appeared on either figure or ground regions. To
      rule out a purely attentional account of figural salience, observers
      discriminated targets on the basis of a region's color (red or green), which was
      equally likely to define the figure or the ground. The results of our experiments
      showed that targets appearing on figures were discriminated more accurately than
      those appearing in ground regions. In addition, targets appearing on figures were
      discriminated better than those presented in regions considered figurally
      neutral, but targets appearing within ground regions were discriminated more
      poorly than those appearing in figurally neutral regions. Taken together, our
      findings suggest that when two regions share a contour, regions assigned as
      figure are perceptually enhanced, whereas regions assigned as ground are
      perceptually suppressed.

PMID- 27048442
TI  - Failure to detect meaning in RSVP at 27 ms per picture.
AB  - The human visual system has the remarkable ability to rapidly detect meaning from
      visual stimuli. Potter, Wyble, Hagmann, and McCourt (Attention, Perception, &
      Psychophysics, 76, 270-279, 2014) tested the minimum viewing time required to
      obtain meaning from a stream of pictures shown in a rapid serial visual
      presentation (RSVP) sequence containing either six or 12 pictures. They reported
      that observers could detect the presence of a target picture specified by name
      (e.g., smiling couple) even when the pictures in the sequence were presented for
      just 13 ms each. Potter et al. claimed that this was insufficient time for
      feedback processing to occur, so feedforward processing alone must be able to
      generate conscious awareness of the target pictures. A potential confound in
      their study is that the pictures in the RSVP sequence sometime contained areas
      with no high-contrast edges, and so may not have adequately masked each other.
      Consequently, iconic memories of portions of the target pictures may have
      persisted in the visual system, thereby increasing the effective presentation
      time. Our study addressed this issue by redoing the Potter et al. study, but
      using four different types of masks. We found that when adequate masking was
      used, no evidence emerged that observers could detect the presence of a specific
      target picture, even when each picture in the RSVP sequence was presented for 27
      ms. On the basis of these findings, we cannot rule out the possibility that
      feedback processing is necessary for individual pictures to be recognized.

PMID- 27048444
TI  - PICALM rs3851179 Variant Confers Susceptibility to Alzheimer's Disease in Chinese
      Population.
AB  - The association between PICALM rs3851179 variant and Alzheimer's disease (AD) has
      been well established by previous genome-wide association studies (GWAS) and
      candidate gene studies in European population. Recent studies investigated the
      association between PICALM rs3851179 and AD susceptibility in Chinese population.
      However, these studies reported consistent and inconsistent results. Here, we
      selected 9435 samples including 3704 AD cases and 5731 controls from previous
      studies and evaluated this association using a meta-analysis method for additive
      model. We did not observe significant genetic heterogeneity in Chinese
      population. Our results indicate significant association between PICALM rs3851179
      and AD in Chinese population. The sensitivity analysis indicates that the
      association between rs3851179 and AD did not vary substantially. The regression
      analysis suggests no significant publication bias. In summary, this updated meta
      analysis highlights the involvement of PICALM rs3851179 variant in Alzheimer's
      disease susceptibility in Chinese population.

PMID- 27048445
TI  - Epidemiological investigation of muscle-strengthening activities and cognitive
      function among older adults.
AB  - Limited research has examined the association of muscle-strengthening activities
      and executive cognitive function among older adults, which was this study's
      purpose. Data from the 1999-2002 NHANES were employed (N = 2157; 60-85 years).
      Muscle-strengthening activities were assessed via self-report, with cognitive
      function assessed using the digit symbol substitution test. After adjusting for
      age, age-squared, gender, race-ethnicity, poverty level, body mass index, C
      reactive protein, smoking, comorbid illness and physical activity, muscle
      strengthening activities were significantly associated with cognitive function
      (betaadjusted = 3.4; 95% CI: 1.7-5.1; P < 0.001). Compared to those not engaging
      in aerobic exercise and not meeting muscle-strengthening activity guidelines,
      those doing 1 (betaadjusted = 3.7; 95% CI: 1.9-5.4; P < 0.001) and both
      (betaadjusted = 6.6; 95% CI: 4.8-8.3; P < 0.001) of these behaviors had a
      significantly higher executive cognitive function score. In conclusion, muscle
      strengthening activities are associated with executive cognitive function among
      older U.S. adults, underscoring the importance of promoting both aerobic exercise
      and muscle-strengthening activities to older adults. 

PMID- 27048446
TI  - Assets of oncologist who falsely diagnosed cancers to be divided among patients.

PMID- 27048443
TI  - Neuropsychiatric Issues in Parkinson's Disease.
AB  - Cognitive and neuropsychiatric symptoms are common in Parkinson's Disease and may
      surpass motor symptoms as the major factors impacting patient quality of life.
      The symptoms may be broadly separated into those associated with the disease
      process and those that represent adverse effects of treatment. Symptoms
      attributed to the disease arise from pathologic changes within multiple brain
      regions and are not restricted to dysfunction in the dopaminergic system. Mood
      symptoms such as depression, anxiety, and apathy are common and may precede the
      development of motor symptoms by years, while other neuropsychiatric symptoms
      such as cognitive impairment, dementia, and psychosis are more common in later
      stages of the disease. Neuropsychiatric symptoms attributed to treatment include
      impulse control disorders, pathologic use of dopaminergic medications, and
      psychosis. This manuscript will review the current understanding of
      neuropsychiatric symptoms in Parkinson's Disease. 

PMID- 27048447
TI  - How to write a case report in nephrology.
AB  - Nephrologists provide medical care to patients presenting with acute kidney
      injury, chronic kidney disease, glomerular diseases, and electrolyte or acid-base
      disorders, and perform lifesaving dialysis therapies and kidney transplantation.
      This editorial is an attempt to describe how to write a comprehensive, yet
      succinct, case report in nephrology. The essential elements of a nephrology case
      report are defined that can serve as a writing aid to the author. 

PMID- 27048448
TI  - Diversity of Culturable Thermophilic Actinobacteria in Hot Springs in Tengchong,
      China and Studies of their Biosynthetic Gene Profiles.
AB  - The class Actinobacteria has been a goldmine for the discovery of antibiotics and
      has attracted interest from both academics and industries. However, an absence of
      novel approaches during the last few decades has limited the discovery of new
      microbial natural products useful for industries. Scientists are now focusing on
      the ecological aspects of diverse environments including unexplored or
      underexplored habitats and extreme environments in the search for new
      metabolites. This paper reports on the diversity of culturable actinobacteria
      associated with hot springs located in Tengchong County, Yunnan Province,
      southwestern China. A total of 58 thermophilic actinobacterial strains were
      isolated from the samples collected from ten hot springs distributed over three
      geothermal fields (e.g., Hehua, Rehai, and Ruidian). Phylogenetic positions and
      their biosynthetic profiles were analyzed by sequencing 16S rRNA gene and three
      biosynthetic gene clusters (KS domain of PKS-I, KSalpha domain of PKS-II and A
      domain of NRPS). On the basis of 16S rRNA gene phylogenetic analysis, the 58
      strains were affiliated with 12 actinobacterial genera: Actinomadura
      Micromonospora, Microbispora, Micrococcus, Nocardiopsis, Nonomuraea,
      Promicromonospora, Pseudonocardia, Streptomyces, Thermoactinospora,
      Thermocatellispora, and Verrucosispora, of which the two novel genera
      Thermoactinospora and Thermocatellisopora were recently described from among
      these strains. Considering the biosynthetic potential of these actinobacterial
      strains, 22 were positive for PCR amplification of at least one of the three
      biosynthetic gene clusters (PKS-I, PKS-II, and NRPS). These actinobacteria were
      further subjected to antimicrobial assay against five opportunistic human
      pathogens (Acinetobacter baumannii, Escherichia coli, Micrococcus luteus,
      Staphylococcus aureus and Streptococcus faecalis). All of the 22 strains that
      were positive for PCR amplification of at least one of the biosynthetic gene
      domains exhibited antimicrobial activities against at least one of the five test
      organisms. Among the remaining 36 actinobacteria that are negative for PCR
      amplification of the domains for the biosynthetic genes, 33 strains showed
      antimicrobial activities against at least one of the five test pathogens. In
      summary, the findings presented in this study emphasized the importance of
      underexplored habitats such as Tengchong hot springs as potential sources for
      search of bioactive molecules.

PMID- 27048449
TI  - Quaternary structure of a G-protein-coupled receptor heterotetramer in complex
      with Gi and Gs.
AB  - BACKGROUND: G-protein-coupled receptors (GPCRs), in the form of monomers or
      homodimers that bind heterotrimeric G proteins, are fundamental in the transfer
      of extracellular stimuli to intracellular signaling pathways. Different GPCRs may
      also interact to form heteromers that are novel signaling units. Despite the
      exponential growth in the number of solved GPCR crystal structures, the
      structural properties of heteromers remain unknown. RESULTS: We used single
      particle tracking experiments in cells expressing functional adenosine A1-A2A
      receptors fused to fluorescent proteins to show the loss of Brownian movement of
      the A1 receptor in the presence of the A2A receptor, and a preponderance of cell
      surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided
      by bioluminescence resonance energy transfer assays to monitor receptor
      homomerization and heteromerization and G-protein coupling, we predict the
      interacting interfaces and propose a quaternary structure of the GPCR tetramer in
      complex with two G proteins. CONCLUSIONS: The combination of results points to a
      molecular architecture formed by a rhombus-shaped heterotetramer, which is bound
      to two different interacting heterotrimeric G proteins (Gi and Gs). These novel
      results constitute an important advance in understanding the molecular
      intricacies involved in GPCR function.

PMID- 27048450
TI  - Hearing Loss in Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has many characteristics of
      autoimmune diseases. Sensorineural hearing loss has been reported in many
      autoimmune diseases. Little is known about hearing loss in patients with IBD.
      METHODS: A prospective blinded comparative study was conducted over a 3-year
      period. IBD patients and controls underwent a complete otorhinolaryngeal
      examination and eudiometry test. RESULTS: Altogether 105 participants (76
      patients and 29 controls) took part in this study. Mean age was 36, 51 % were
      males, and 40 % of the patients were presently hospitalized due to IBD
      exacerbation. Audiometric examination revealed that any hearing loss (mild to
      severe) was found in 29 (38 %) of the IBD population, compared to 4 (14 %) of the
      control group (p = 0.02). Extraintestinal manifestation (EIM) was present in
      33/76 (43 %) of IBD patients. Any hearing loss and moderate to severe hearing
      loss were found in 17/33 (52 %) and 7/33 (21 %) in the EIM-positive group
      compared to 12/43 (28 %) and 4/43 (9 %) in the EIM-negative group (p = 0.036 and
      p = 0.14, respectively). Out of patients over the age of 40 with other EIMs, all
      11/11 (100 %) of patients had any hearing loss compared to 8/12 (66 %) of
      patients over the age of 40 without other EIMs, p = 0.035. CONCLUSIONS: Hearing
      loss may be another EIM of IBD. It is found in 38 % of IBD patients and in up to
      52 % of patients with other EIMs and increases over the age of 40. Early hearing
      evaluation should be recommended to these high-risk IBD patients.

PMID- 27048451
TI  - Albumin May Prevent the Morbidity of Paracentesis-Induced Circulatory Dysfunction
      in Cirrhosis and Refractory Ascites: A Pilot Study.
AB  - BACKGROUND: Large-volume total paracentesis may result in paracentesis-induced
      circulatory dysfunction, which is associated with poor outcomes. AIMS: To explore
      the short- and long-term effects of paracentesis-induced circulatory dysfunction
      on systemic hemodynamics, renal function and other cirrhosis-related
      complications in patients with refractory ascites, following subtotal large
      volume paracentesis. METHODS: Patients with cirrhosis and refractory ascites
      without renal dysfunction had systemic hemodynamics, renal function, and
      neurohormones (plasma active renin, aldosterone, norepinephrine and angiotensin
      II) measured pre- and 6 days post-paracentesis. Paracentesis was limited to <=8 L
      with 6-8 g of albumin per liter ascites drained. Patients were followed up until
      transjugular intrahepatic portosystemic shunt insertion, liver transplantation,
      or death. Paracentesis-induced circulatory dysfunction was defined as >50 %
      increase in plasma active renin 6 days post-paracentesis. RESULTS: Fifty-seven
      patients (mean age 59.0 +/- 9.4 years) had mean 6.8 +/- 1.8 L of ascites removed
      with 9 +/- 3 g of albumin given/L of ascites drained. Patients were followed up
      for 715 +/- 104 days. Twenty-three patients (40.4 %) developed paracentesis
      induced circulatory dysfunction with unchanged serum creatinine on day six,
      despite worsening of hemodynamics (mean arterial pressure 90 +/- 10 mmHg at
      baseline vs. 84 +/- 8 mmHg on day six, p < 0.05). Similar hemodynamic changes
      were observed among patients without paracentesis-induced circulatory
      dysfunction. There was no significant difference in the long-term renal function
      or cirrhosis-related complications between the groups. CONCLUSION: The occurrence
      of paracentesis-induced circulatory dysfunction, as defined by plasma active
      renin, may not have a significant short- and long-term impact on renal function
      or cirrhosis-related complications in patients with refractory ascites who
      undergo subtotal paracentesis with albumin infusion.

PMID- 27048453
TI  - Treatment of Dual Genotype Chronic Hepatitis C: Case Series.

PMID- 27048454
TI  - Editorial: Polypharmacology in Drug Discovery.

PMID- 27048452
TI  - The Gastric Mucosa from Patients Infected with CagA+ or VacA+ Helicobacter pylori
      Has a Lower Level of Dual Oxidase-2 Expression than Uninfected or Infected with
      CagA-/VacA- H. pylori.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is a well-recognized gastroduodenal
      pathogen and class I carcinogen. Dual oxidase-2 (DUOX2), a member of NADPH
      oxidase family, has several critical physiological functions, including thyroid
      hormone biosynthesis and host mucosal defense. AIM: To investigate the effect of
      H. pylori infection on DUOX2 gene expression in human stomach. MATERIALS AND
      METHODS: The biopsies were obtained from patients who underwent endoscopic
      diagnosis. The patient serum was assayed for two virulence factors of H. pylori,
      CagA IgG and VacA. The inflammation in gastric mucosa was analyzed with
      histology. Real-time quantitative PCR was used to detect the expression of three
      members of NADPH oxidase, NOX1, NOX2, and DUOX2, as well as lactoperoxidase (LPO)
      in the gastric mucosa. NOX2, DUOX2, and myeloperoxidase (MPO) protein levels were
      quantified by Western blots or immunohistochemistry. RESULTS: The H. pylori
      infected gastric mucosa had more severe inflammation than uninfected samples.
      However, the expression of DUOX2 mRNA and protein was lower in gastric mucosa of
      patients with H. pylori infection compared to the uninfected. Among the H. pylori
      infected patients, those having CagA IgG or VacA in the serum had lower DUOX2
      expression levels than those infected with H. pylori without either virulence
      factor. The NOX2 and MPO levels were higher in those patients infected with H.
      pylori irrespective of the virulence factors than those uninfected patients. NOX1
      and LPO mRNA were undetectable in the gastric mucosa. CONCLUSION: CagA+ or VacA+
      H. pylori in the stomach of patients may suppress DUOX2 expression to promote its
      own survival. Increased NOX2 could not eliminate H. pylori infection.

PMID- 27048455
TI  - Differences in quality of life between American and Chinese breast cancer
      survivors.
AB  - OBJECTIVE: It has been speculated that cancer survivors in Asia may have lower
      quality of life (QOL) compared with their Western counterparts. However, no
      studies have made international comparisons in QOL using a comprehensive measure.
      This study aimed to compare Chinese breast cancer survivors' QOL with US
      counterparts and examine if demographic and medical factors were associated with
      QOL across groups. METHOD: The sample consisted of 159 breast cancer patients (97
      Chinese and 62 American) who completed the Functional Assessment for Cancer
      Therapy Breast Cancer (FACT-B) scale before the start of radiotherapy in
      Shanghai, China and Houston, USA. RESULTS: Higher income was associated with
      higher QOL total scores in both Chinese and American cancer patients, but QOL was
      not significantly associated with other factors including age, education, disease
      stage, mastectomy, and chemotherapy. Consistent with hypotheses, compared to
      their US counterparts, Chinese breast cancer survivors reported lower QOL and all
      four subdimensions including functional well-being (FWB), physical well-being
      (PWB), emotional well-being (EWB), and social well-being (SWB); they also
      reported more breast cancer-specific concerns (BCS). Differences were also
      clinically significant for Functional Assessment for Cancer Therapy General (FACT
      G) scale total scores and the FWB subscale. After controlling for demographic and
      medical covariates, these differences remained except for the SWB and BCS.
      Furthermore, Chinese breast cancer survivors receiving chemotherapy reported
      significantly lower FACT-G scores than those who did not, but this difference did
      not emerge among US breast cancer survivors. DISCUSSION: Chinese breast cancer
      survivors reported poorer QOL on multiple domains compared to US women. Findings
      indicate that better strategies are needed to help improve the QOL of Chinese
      breast cancer survivors, especially those who underwent chemotherapy.

PMID- 27048457
TI  - Editorial: Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in
      Diseases: Molecular Targets.

PMID- 27048456
TI  - Weathering the seasons of cancer survivorship: mind-body therapy use and reported
      reasons and outcomes by stages of cancer survivorship.
AB  - PURPOSE: Mind-body therapies (MBTs), a subset of complementary and alternative
      medicine (CAM), are used by cancer survivors to manage symptoms related to their
      cancer experience. MBT use may differ by cancer survivorship stage (i.e., acute,
      short-term, long-term) because each stage presents varying intensities of medical
      activities, associated emotions, and treatment effects. We examined the
      relationship between MBT use and survivorship stage (acute <1 year; short-term 1
      to 5 years; long-term >5 years since diagnosis) using the CAM supplement of the
      2012 National Health Interview Survey. We also examined reported reasons for and
      outcomes of MBT use and frequency of MBT types. METHODS: The sample included
      cancer survivors (N = 3076) and non-cancer controls (N = 31,387). Logistic
      regression tested the relationship of MBT use and survivorship stage. Weighted
      percentages were calculated by survivorship stage for reported reasons and
      outcomes of use and frequency of MBT types. RESULTS: MBT use varied by cancer
      survivorship stage (p = 0.02): acute (8.3 %), short-term (15.4 %), long-term
      (11.7 %) survivorship and non-cancer controls (13.2 %). In the adjusted model,
      short-term survivors had 35 % greater odds of MBT use than did controls (95 % CI
      1.00, 1.83). Reasons for and outcomes of MBT use varied among the survivorship
      stages, with more acute survivors reporting medical-related reasons and more
      short-term survivors reporting to manage symptoms. CONCLUSIONS: MBT may fulfill
      different symptom management needs at varying stages of survivorship. These
      findings can help inform supportive care services of survivors' use of MBT for
      symptom burden at each stage and the allocation of these services.

PMID- 27048458
TI  - Endoplasmic Stress Inhibitors for Homocysteine Induced Cardiovascular Disease.
AB  - Cardiovascular disease (CVD) remains a major cause of death and disability
      worldwide, thus preventing and inhibiting CVD remains a health priority. Several
      lines of pharmacological interventions have not met with great success, thus
      inhibition of novel cellular stress pathways could be a novel therapeutic avenue
      to treat CVD. This review will focus on homocysteine and endoplasmic reticulum
      stress linked to mitochondria function, and possible therapeutic avenues for
      treatment.

PMID- 27048459
TI  - Regional myocardial microvascular dysfunction in cardiac amyloid light-chain
      amyloidosis: assessment with 3T cardiovascular magnetic resonance.
AB  - BACKGROUND: Coronary microvascular dysfunction is highly prevalent in patients
      with amyloid light-chain (AL) cardiac amyloidosis (AL-CA). The aim of this study
      was to clarify the feasibility of first-pass perfusion imaging using 3 T
      cardiovascular magnetic resonance (CMR) for evaluating the difference in left
      ventricular (LV) regional myocardial microvascular function among normal subjects
      and in patients with AL-CA. The amyloidosis patients were classified into those
      with impaired systolic function [LV ejection fraction (LVEF) < 50 %] and those
      with preserved systolic function. METHODS: In total, 32 patients with biopsy
      proven AL-CA, including 11 AL-CA patients with systolic dysfunction, 21 AL-CA
      patients with preserved systolic function, and 25 healthy subjects, underwent CMR
      examination. LV regional myocardial perfusion parameters included upslope, time
      to maximum signal intensity (TTM) and max signal intensity (MaxSI) were compared
      among the three patient groups. Receiver operating characteristic analysis was
      performed to determine whether perfusion parameters could be used in
      discriminating regional myocardial microvascularity between AL-CA patients and
      normal subjects. RESULTS: The patients with AL-CA had significantly reduced first
      pass perfusion upslope and MaxSI, and increased TTM compared with the normal
      subjects (all P < 0.01). Compared with the patients with AL-CA and preserved
      LVEF, the patients with AL-CA and impaired systolic function had a longer TTM in
      the basal (47.05 +/- 16.59 vs. 39.68 +/- 19.11; P = 0.002) and mid-ventricular
      (44.61 +/- 16.34 vs. 37.74 +/- 18.25; P = 0.002) segments; lower upslope in the
      basal (2.41 +/- 1.32 vs. 3.60 +/- 1.68; P < 0.0001), mid-ventricular (2.82 +/-
      1.34 vs. 4.15 +/- 2.02; P < 0.0001), and apical (3.71 +/- 1.38 vs. 4.97 +/- 2.55;
      P = 0.004) segments; and lower MaxSI (31.67 +/- 15.23 vs. 37.96 +/- 11.15; P <
      0.0001) in the basal segment. The ROC curve analysis revealed that the first-pass
      upslope, TTM, and MaxSI may be used as indicators for differentiating
      microcirculation between AL-CA patients with preserved or impaired systolic
      function and normal subjects. CONCLUSIONS: The differences in LV regional
      myocardial microvascular function among normal subjects, AL-CA patients with
      systolic dysfunction, and AL-CA patients with preserved systolic function can be
      monitored using first-pass perfusion CMR.

PMID- 27048460
TI  - Secreted frizzled related protein 1 protects H9C2 cells from hypoxia/re
      oxygenation injury by blocking the Wnt signaling pathway.
AB  - BACKGROUND: In animal models, secreted frizzled related protein 1 (Sfrp1)
      inhibition of the Wnt signaling pathway is beneficial because Sfrp1 reduces
      myocardial apoptosis and prevents heart failure. The mechanisms mediating the
      cellular survival effect of Sfrp1 has not been completely elucidated. The present
      study was designed to investigate the possible protective actions of Sfrp1 on
      cardiac muscle cells using an in vitro model of ischemia/reperfusion, and to
      evaluate the possible involvement of the Wnt signaling pathway. METHODS: We used
      a recombinant AAV9 vector to deliver the Sfrp1 gene into H9C2 rat cardiomyoblasts
      and adopted an in vitro model of ischemia/reperfusion. Cell vitality was measured
      by CKK-8 and the trypan blue exclusion assay. Western blot was used to evaluate
      the expression of Dvl-1, beta-catenin, c-Myc, Bax, and Bcl-2. Flow cytometry
      analysis of cardiomyocyte apoptosis was performed. RESULTS: We confirmed that
      Sfrp1 significantly increased cell viability (assayed by trypan blue and CKK-8)
      and decreased apoptosis (assayed by flow cytometry analysis and the Bax/Bcl-2
      ratio). These effects were partly attributable to the ability of Sfrp1 to down
      regulate Wnt signaling pathway (assayed by Western blot to evaluate the
      expression of Dvl-1, beta-catenin, and c-Myc). Indeed, reactivation of the Wnt
      signaling pathway activity with the specific activator, Licl, reduced Sfrp1
      induced cardioprotection during hypoxia and reoxygenation. CONCLUSIONS: The
      present study demonstrated that Sfrp1 directly protected H9C2 cells from hypoxia
      and reoxygenation-induced reperfusion injury and apoptosis through inhibition of
      the Wnt signaling pathway, and added new mechanistic insight regarding the
      cardioprotective role of Sfrp1 on ischemic damage.

PMID- 27048462
TI  - Woman in Northern Ireland who bought abortion pills online is given suspended
      sentence.

PMID- 27048461
TI  - Conservation and divergence of the histone code in nucleomorphs.
AB  - BACKGROUND: Nucleomorphs, the remnant nuclei of photosynthetic algae that have
      become endosymbionts to other eukaryotes, represent a unique example of
      convergent reductive genome evolution in eukaryotes, having evolved independently
      on two separate occasions in chlorarachniophytes and cryptophytes. The
      nucleomorphs of the two groups have evolved in a remarkably convergent manner,
      with numerous very similar features. Chief among them is the extreme reduction
      and compaction of nucleomorph genomes, with very small chromosomes and extremely
      short or even completely absent intergenic spaces. These characteristics pose a
      number of intriguing questions regarding the mechanisms of transcription and gene
      regulation in such a crowded genomic context, in particular in terms of the
      functioning of the histone code, which is common to almost all eukaryotes and
      plays a central role in chromatin biology. RESULTS: This study examines the
      sequences of nucleomorph histone proteins in order to address these issues.
      Remarkably, all classical transcription- and repression-related components of the
      histone code seem to be missing from chlorarachniophyte nucleomorphs. Cryptophyte
      nucleomorph histones are generally more similar to the conventional eukaryotic
      state; however, they also display significant deviations from the typical histone
      code. Based on the analysis of specific components of the code, we discuss the
      state of chromatin and the transcriptional machinery in these nuclei.
      CONCLUSIONS: The results presented here shed new light on the mechanisms of
      nucleomorph transcription and gene regulation and provide a foundation for future
      studies of nucleomorph chromatin and transcriptional biology.

PMID- 27048463
TI  - Modifiable Factors Associated with Knee Abduction During Weight-Bearing
      Activities: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Increased knee abduction angle during activity is suggested to be a
      risk factor for sustaining an anterior cruciate ligament (ACL) injury or
      developing patellofemoral pain syndrome (PFPS). Knowledge of the modifiable
      mechanisms that are associated with increased knee abduction will aid in the
      appropriate design of preventive and rehabilitative strategies for these
      injuries. OBJECTIVE: Our objective was to systematically review modifiable
      mechanisms contributing to increased knee abduction in healthy people and in
      individuals with an ACL injury or PFPS. METHODS: We performed a systematic review
      and meta-analysis according to Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines. We searched the databases MEDLINE, CINAHL,
      and Embase until September 2015. Inclusion criteria were studies in healthy
      individuals and/or those with ACL injury or PFPS reporting (1) muscle strength,
      muscle activation, proprioception, and/or range of motion (ROM) and (2) knee
      abduction angle assessed with either motion analysis or visual observation during
      weight-bearing activity. RESULTS: In total, 33 articles were included. Reduced
      trunk strength, reduced gluteus maximus amplitude, decreased ankle ROM, and
      increased hip external rotation ROM were moderately associated with increased
      knee abduction angle (r -0.34 or higher, standardized difference in means (SDM)
      greater than -0.39, p < 0.05, articles n = 3, total sample size n = 101-114) in
      healthy individuals. Decreased strength of hip abductors, external rotators, and
      extensors and knee flexors were at most weakly associated with increased knee
      abduction angle (r <= 0.21, p = 0.013-0.426, articles n = 2-9, total sample size
      n = 80-311). Too few articles included patients with knee injury to be included
      in any meta-analysis. CONCLUSION: The associations identified in this review
      indicate that investigation of strengthening of the trunk muscles, and
      improvement of gluteus maximus activation and ankle ROM to change knee kinematics
      is merited. Studies on modifiable factors associated with increased knee
      abduction angle in people with knee injury are needed.

PMID- 27048464
TI  - Understanding modern extinctions in marine ecosystems: the role of
      palaeoecological data.
AB  - Because anthropogenic impacts on ecological systems pre-date the oldest
      scientific observations, historical documents and archaeological records,
      understanding modern extinctions requires additional data sources that extend
      further back in time. Palaeoecological records, which provide quantitative proxy
      records of ecosystems prior to human impact, are essential for understanding
      recent extinctions and future extinction risks. Here we critically review the
      value of the most recent fossil record in contributing to our understanding of
      modern extinctions and illustrate through case studies how naturally occurring
      death assemblages and Holocene sedimentary records provide context to the plight
      of marine ecosystems. While palaeoecological data are inherently restricted
      censuses of past communities (manipulative experiments are not possible), they
      yield quantitative records over temporal scales that are beyond the reach of
      ecology. Only by including palaeoecological data is it possible to fully assess
      the role of long-term anthropogenic processes in driving modern extinction risk. 

PMID- 27048465
TI  - Time-calibrated models support congruency between Cretaceous continental rifting
      and titanosaurian evolutionary history.
AB  - Recent model-based phylogenetic approaches have expanded upon the incorporation
      of extinct lineages and their respective temporal information for calibrating
      divergence date estimates. Here, model-based methods are explored to estimate
      divergence dates and ancestral ranges for titanosaurian sauropod dinosaurs, an
      extinct and globally distributed terrestrial clade that existed during the
      extensive Cretaceous supercontinental break-up. Our models estimate an Early
      Cretaceous (approx. 135 Ma) South American origin for Titanosauria. The estimated
      divergence dates are broadly congruent with Cretaceous geophysical models of
      supercontinental separation and subsequent continental isolation while obviating
      the invocation of continuous Late Cretaceous continental connections (e.g.
      ephemeral land bridges). Divergence dates for mid-Cretaceous African and South
      American sister lineages support semi-isolated subequatorial African faunas in
      concordance with the gradual northward separation between South America and
      Africa. Finally, Late Cretaceous Africa may have linked Laurasian lineages with
      their sister South American lineages, though the current Late Cretaceous African
      terrestrial fossil record remains meagre. 

PMID- 27048466
TI  - Stress is not pain. Comment on Elwood and Adams (2015) 'Electric shock causes
      physiological stress responses in shore crabs, consistent with prediction of
      pain'.

PMID- 27048467
TI  - Experimental demonstration of an Allee effect in microbial populations.
AB  - Microbial populations can be dispersal limited. However, microorganisms that
      successfully disperse into physiologically ideal environments are not guaranteed
      to establish. This observation contradicts the Baas-Becking tenet: 'Everything is
      everywhere, but the environment selects'. Allee effects, which manifest in the
      relationship between initial population density and probability of establishment,
      could explain this observation. Here, we experimentally demonstrate that small
      populations of Vibrio fischeri are subject to an intrinsic demographic Allee
      effect. Populations subjected to predation by the bacterivore Cafeteria
      roenbergensis display both intrinsic and extrinsic demographic Allee effects. The
      estimated critical threshold required to escape positive density-dependence is
      around 5, 20 or 90 cells ml(-1)under conditions of high carbon resources, low
      carbon resources or low carbon resources with predation, respectively. This work
      builds on the foundations of modern microbial ecology, demonstrating that
      mechanisms controlling macroorganisms apply to microorganisms, and provides a
      statistical method to detect Allee effects in data.

PMID- 27048468
TI  - Long-term consequences of high incubation temperature in a wild bird population.
AB  - Because incubation by birds is energetically costly, parents frequently trade off
      investment in incubation against self-maintenance. This can be manifested by a
      reduction in incubation temperature, which comes at high somatic costs for
      nestlings. The extent to which these costs constrain fitness is poorly
      understood. We incubated wild blue tit clutches at three biologically relevant
      temperatures and subsequently recorded winter survival and survival to the
      breeding season. Fledglings from the coldest treatment (35.0 degrees C) survived
      less well than other fledglings, but the proportion of winter and breeding
      survivors did not differ significantly between treatments. However, survival
      probability in both seasons increased with body mass at fledging in birds from
      low and mid incubation temperatures, but decreased with fledging body mass in the
      high-temperature treatment. Mid-temperature nestlings were heavier as adults,
      weighing 7% more than low- and high-temperature survivors. Thus, high incubation
      temperature can be beneficial in the short term, but costs of accelerated
      embryonic development may equal those of protracted development in the long term.
      Such hidden consequences of faster development could maintain natural selection
      for average incubation temperature.

PMID- 27048469
TI  - Stress was never said to be pain: response to Stevens et al. (2016).

PMID- 27048471
TI  - Assam: India's state with the highest maternal mortality.

PMID- 27048470
TI  - Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue
      and its relevance to chronic fatigue syndrome.
AB  - BACKGROUND: The NLRP3 inflammasome (NOD-like receptor family, pyrin domain
      containing 3) is an intracellular protein complex that plays an important role in
      innate immune sensing. Its activation leads to the maturation of caspase-1 and
      regulates the cleavage of interleukin (IL)-1beta and IL-18. Various studies have
      shown that activation of the immune system plays a pivotal role in the
      development of fatigue. However, the mechanisms underlying the association
      between immune activation and fatigue remained elusive, and few reports have
      described the involvement of NLRP3 inflammasome activation in fatigue. METHODS:
      We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg)
      challenge combined with swim stress. Both behavioural and biochemical parameters
      were measured to illustrate the characteristics of this model. We also assessed
      NLRP3 inflammasome activation in the mouse diencephalon, which is the brain
      region that has been suggested to be responsible for fatigue sensation. To
      further identify the role of NLRP3 inflammasome activation in the pathogenesis of
      chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS
      treatment and swim stress, and the same parameters were evaluated. RESULTS: Mice
      challenged with LPS and subjected to the swim stress test showed decreased
      locomotor activity, decreased fall-off time in a rota-rod test and increased
      serum levels of IL-1beta and IL-6 compared with untreated mice. Serum levels of
      lactic acid and malondialdehyde (MDA) were not significantly altered in the
      treated mice. We demonstrated increased NLRP3 expression, IL-1beta production and
      caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice,
      we found remarkably increased locomotor activity with longer fall-off times and
      decreased serum IL-1beta levels compared with those of wild-type (WT) mice after
      LPS challenge and the swim stress test. IL-1beta levels in the diencephalon were
      also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were
      not significantly altered. CONCLUSIONS: These findings suggest that LPS-induced
      fatigue is an IL-1beta-dependent process and that the NLRP3/caspase-1 pathway is
      involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1
      inhibition may be a promising therapy for fatigue treatment.

PMID- 27048472
TI  - Solid-State Quantitative (1)H and (31)P MRI of Cortical Bone in Humans.
AB  - Magnetic resonance imaging (MRI) plays a pivotal role for assessment of the
      musculoskeletal system. It is currently the clinical modality of choice for
      evaluation of soft tissues including cartilage, ligaments, tendons, muscle, and
      bone marrow. By comparison, the study of calcified tissue by MRI is still in its
      infancy. In this article, we review the potential of the modality for assessment
      of cortical bone properties known to be affected in degenerative bone disease,
      with focus on parameters related to matrix and mineral densities, and porosity,
      by means of emerging solid-state (1)H and (31)P MRI techniques. In contrast to
      soft tissues, the MRI signal in calcified tissues has very short lifetime, on the
      order of 100 MUs to a few milliseconds, demanding customized imaging approaches
      that allow capture of the signal almost immediately after excitation. The
      technologies described are suited for quantitatively imaging human cortical bone
      in specimens as well as in vivo in patients on standard clinical imagers,
      yielding either concentrations in absolute units when measured against a
      reference standard, or more simply, in the form of surrogate biomarkers. The two
      major water fractions in cortical bone are those of collagen-bound and pore water
      occurring at an approximately 3:1 ratio. Collagen-bound water density provides a
      direct quantitative measure of osteoid density. While at an earlier stage of
      development, quantification of mineral phosphorus by (31)P MRI yields mineral
      density and, together with knowledge of matrix density, should allow
      quantification of the degree of bone mineralization.

PMID- 27048473
TI  - Advances in Nanotechnology for the Treatment of Osteoporosis.
AB  - Osteoporosis is a degenerative bone disease commonly related to aging. With an
      increase in life expectancies worldwide, the prevalence of the disease is
      expected to rise. Current clinical therapeutic treatments are not able to offer
      long-term solutions to counter the bone mass loss and the increased risk of
      fractures, which are the primary characteristics of the disease. However, the
      combination of bioactive nanomaterials within a biomaterial scaffold shows
      promise for the development of a localized, long-term treatment for those
      affected by osteoporosis. This review summarizes the unique characteristics of
      engineered nanoparticles that render them applicable for bone regeneration and
      recaps the current body of knowledge on nanomaterials with potential for
      osteoporosis treatment and bone regeneration. Specifically, we highlight new
      developments that are shaping this emerging field and evaluate applications of
      recently developed nanomaterials for osteoporosis treatment. Finally, we will
      identify promising new research directions in nanotechnology for bone
      regeneration.

PMID- 27048474
TI  - Engaging adolescents in tuberculosis and clinical trial research through drama.
AB  - BACKGROUND: The South African Tuberculosis Vaccine Initiative is based in
      Worcester where tuberculosis (TB) is endemic, and incidence rates are amongst the
      highest nationally. In high TB burden settings after an early childhood peak,
      incidence rates start to rise again in adolescents, therefore they are an
      important target group for tuberculosis vaccine research. In 2012, learners from
      a local school developed a one-off theatrical production out of an educational
      comic book Carina's Choice, developed by the South African Tuberculosis Vaccine
      Initiative in 2010. A Wellcome Trust International Engagement grant allowed for
      this one-off production to be further developed, with input from university
      students and staff, and rolled out to schools in the Worcester area as an
      engagement and education intervention. METHODS: Focus group feedback was used to
      identify key messages and to develop the play's script. Qualitative methods were
      used to collect and analyse relevant data. Interviews were conducted with learner
      actors, pre- and post-focus group feedback was obtained from a sample of school
      going adolescents, and pre- and post-questionnaires were administered to
      adolescent audience members. RESULTS: From the pre-drama focus group discussions,
      topics such as TB symptoms, stigma and transmission were identified as areas that
      needed attention. After the performances, adolescents showed improved knowledge
      on the identified topics and they discussed TB prevention measures. They
      highlighted transmission of TB during pregnancy as a further topic to be
      addressed in future iterations of the drama. Although stigma is a difficult
      phenomenon to interpret, post-drama participants understood that TB transmission
      could occur in all individuals. Learner-actors agreed with focus group
      participants that the play could impact the wider community if it were rolled
      out. Feedback from the South African Tuberculosis Vaccine Initiative staff
      verified that recruitment for an upcoming trial was facilitated by the
      preparedness that the play provided in recruitment areas. The study showed that
      before and after evaluations provide data on the usefulness of the play as an
      education tool. CONCLUSIONS: Theatre, presented and motivated by adolescent
      peers, can raise awareness of TB, and assist clinical trial preparedness and
      further engagement between trial staff and their trial community.

PMID- 27048476
TI  - Tumoral pseudogout of the proximal interphalangeal joint of a finger: a case
      report and literature review.
AB  - Tumoral pseudogout is a rare clinical form of calcium pyrophosphate dihydrate
      crystal deposition disease. Tumoral pseudogout can mimic other diseases such as
      chondroid tumor, tophaceous gout, or tumoral calcinosis. Its radiological
      features have been presented in some case reports, but no specific radiographic
      features have been identified. Here, we report an unusual case of recurrent
      tumoral pseudogout involving the proximal interphalangeal joint of the right long
      finger. This case presents with progressive radiological findings of the disease
      with an enlarging and recurrent calcified mass and secondary bony erosion and
      remodeling, along with a radiological-pathological correlation. We also review
      previously reported imaging findings of this disease entity, differential points
      in comparison to other diseases, and some key points for making the correct
      diagnosis. 

PMID- 27048475
TI  - The Genome and Methylome of a Subsocial Small Carpenter Bee, Ceratina calcarata.
AB  - Understanding the evolution of animal societies, considered to be a major
      transition in evolution, is a key topic in evolutionary biology. Recently, new
      gateways for understanding social evolution have opened up due to advances in
      genomics, allowing for unprecedented opportunities in studying social behavior on
      a molecular level. In particular, highly eusocial insect species (caste
      containing societies with nonreproductives that care for siblings) have taken
      center stage in studies of the molecular evolution of sociality. Despite advances
      in genomic studies of both solitary and eusocial insects, we still lack genomic
      resources for early insect societies. To study the genetic basis of social traits
      requires comparison of genomes from a diversity of organisms ranging from
      solitary to complex social forms. Here we present the genome of a subsocial bee,
      Ceratina calcarata This study begins to address the types of genomic changes
      associated with the earliest origins of simple sociality using the small
      carpenter bee. Genes associated with lipid transport and DNA recombination have
      undergone positive selection in C. calcarata relative to other bee lineages.
      Furthermore, we provide the first methylome of a noneusocial bee. Ceratina
      calcarata contains the complete enzymatic toolkit for DNA methylation. As in the
      honey bee and many other holometabolous insects, DNA methylation is targeted to
      exons. The addition of this genome allows for new lines of research into the
      genetic and epigenetic precursors to complex social behaviors.

PMID- 27048477
TI  - The effectiveness of Technology-assisted Cascade Training and Supervision of
      community health workers in delivering the Thinking Healthy Program for perinatal
      depression in a post-conflict area of Pakistan - study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Rates of perinatal depression in low and middle income countries are
      reported to be very high. Perinatal depression not only has profound impact on
      women's health, disability and functioning, it is associated with poor child
      health outcomes such as pre-term birth, under-nutrition and stunting, which
      ultimately have an adverse trans-generational impact. There is strong evidence in
      the medical literature that perinatal depression can be effectively managed with
      psychological treatments delivered by non-specialists. Our previous research in
      Pakistan led to the development of a successful perinatal depression
      intervention, the Thinking Healthy Program (THP). The THP is a psychological
      treatment delivered by community health workers. The burden of perinatal
      depression can be reduced through scale-up of this proven intervention; however,
      training of health workers at scale is a major barrier. To enhance access to such
      interventions there is a need to look at technological solutions to training and
      supervision. METHODS/DESIGN: This is a non-inferiority, single-blinded randomized
      controlled trial. Eighty community health workers called Lady Health Workers
      (LHWs) working in a post-conflict rural area in Pakistan (Swat) will be recruited
      through the LHW program. LHWs will be randomly allocated to Technology-assisted
      Cascade Training and Supervision (TACTS) or to specialist-delivered training (40
      in each group). The TACTS group will receive training in THP through LHW
      supervisors using a tablet-based training package, whereas the comparison group
      will receive training directly from mental health specialists. Our hypothesis is
      that both groups will achieve equal competence. Primary outcome measure will be
      competence of health workers at delivering THP using a modified ENhancing
      Assessment of Common Therapeutic factors (ENACT) rating scale immediately post
      training and after 3 months of supervision. Independent assessors will be blinded
      to the LHW allocation status. DISCUSSION: Women living in post-conflict areas are
      at higher risk of depression compared to the general population. Implementation
      of evidence-based interventions for depression in such situations is a challenge
      because health systems are weak and human resources are scarce. The key
      innovation to be tested in this trial is a Technology-assisted Cascade Training
      and Supervision system to assist scale-up of the THP. TRIAL REGISTRATION:
      Registered with ClinicalTrials.gov as GCC-THP-TACTS-2015, Identifier: NCT02644902
      .

PMID- 27048478
TI  - [Characteristics and challenges of rheumatology-specific laboratories in
      practice].
AB  - In Germany rheumatological laboratory investigations are increasingly being
      carried out by rheumatologists in private practice. The professional and economic
      value is shown in association with the historical development of laboratory
      medicine and the current discussion on vocational politics. 

PMID- 27048479
TI  - Progressive elbow pain.

PMID- 27048481
TI  - Erratum to: Burkholderia pseudomallei induces IL-23 production in primary human
      monocytes.

PMID- 27048480
TI  - Q fever is an old and neglected zoonotic disease in Kenya: a systematic review.
AB  - BACKGROUND: Q fever is a neglected zoonosis caused by the bacterium Coxiella
      burnetii. The knowledge of the epidemiology of Q fever in Kenya is limited with
      no attention to control and prevention programs. The purpose of this review is to
      understand the situation of Q fever in human and animal populations in Kenya in
      the past 60 years, and help identify future research priorities for the country.
      METHODS: Databases were searched for national and international scientific
      studies or reports on Q fever. We included studies and reports published between
      1950 and 2015 if they reported on Q fever prevalence, incidence, and infection
      control programs in Kenya. Data were extracted with respect to studies on
      prevalence of Coxiella infections, study design, study region, the study
      populations involved, and sorted according to the year of the study. RESULTS: We
      identified 15 studies and reports which qualified for data extraction. Human
      seroprevalence studies revealed evidence of C. burnetii infections ranging from 3
      to 35.8% in all regions in which surveys were made and two Q fever outbreak
      episodes. Coxiella burnetii infections found in cattle 7.4-51.1%, sheep 6.7-20%,
      camels 20-46%, and goats 20-46% revealed variation based on ecoregions and the
      year of study. Farming and lack of protective clothing were associated with
      increased seropositivity among humans. However, high quality data is lacking on Q
      fever awareness, underlying cultural-economic factors influencing C. burnetii
      infection, and how the pathogen cycles may be embedded in livestock production
      and management systems in the economically and ecologically different Kenyan
      regions. We found no studies on national disease incidence estimates or disease
      surveillance and control efforts. CONCLUSION: Coxiella burnetii infections are
      common in human and in a wide range of animal populations but are still
      unrecognized and underestimated thus presenting a significant human and animal
      health threat in Kenya. The factors influencing pathogen transmission,
      persistence and spread are poorly understood. Integrated disease surveillance and
      prevention/control programs are needed in Kenya.

PMID- 27048483
TI  - Current State of Opioid Therapy and Abuse.
AB  - Currently, there is growing tension between the twin challenges of opioid therapy
      for chronic pain and adverse consequences of abuse, leading to multiple
      complications including respiratory failure and death. The recent data from
      Centers for Disease Control and Prevention (CDC) have shown continued escalation
      of prescription opioid use with opioid overdose deaths topping all previous
      estimations. Numerous policy initiatives, advisories, and guidelines have been
      advanced through the years to control the opioid epidemic. The strategies to
      prevent opioid abuse and to maintain opioid therapy when medically necessary fall
      into primary and secondary prevention categories. The primary prevention category
      is extremely crucial, since it involves education of primary care providers and
      patients at the starting point of opioid therapy. The education of surgeons and
      other prescribers is as crucial as the education of primary care physicians. 

PMID- 27048482
TI  - Microbial inhibitors of cysteine proteases.
AB  - Cysteine proteases are one of the major classes of proteolytic enzymes involved
      in a number of physiological and pathological processes in plants, animals and
      microorganisms. When their synthesis, activity and localization in mammalian
      cells are altered, they may contribute to the development of many diseases,
      including rheumatoid arthritis, osteoporosis and cancer. Therefore, cysteine
      proteases have become promising drug targets for the medical treatment of these
      disorders. Inhibitors of cysteine proteases are also produced by almost every
      group of living organisms, being responsible for the control of intracellular
      proteolytic activity. Microorganisms synthesize cysteine protease inhibitors not
      only to regulate the activity of endogenous, often virulent enzymes, but also to
      hinder the host's proteolytic defense system and evade its immune responses
      against infections. Present work describes known to date microbial inhibitors of
      cysteine proteases in terms of their structure, enzyme binding mechanism,
      specificity and pathophysiological roles. The overview of both proteinaceous and
      small-molecule inhibitors produced by all groups of microorganisms (bacteria,
      archaea, fungi, protists) and viruses is provided. Subsequently, possible
      applications of microbial inhibitors in science, medicine and biotechnology are
      also highlighted. 

PMID- 27048484
TI  - Fractures in pituitary adenoma patients from the Dutch National Registry of
      Growth Hormone Treatment in Adults.
AB  - PURPOSE: The effects of growth hormone (GH) replacement therapy on fracture risk
      in adult GH deficient (GHD) patients with different etiologies of pituitary GHD
      are not well known, due to limited data. The aim of this study was to investigate
      characteristics and fracture occurrence at start of (baseline) and during long
      term GH replacement therapy in GHD adults previously treated for Cushing's
      disease (CD) or acromegaly, compared to patients with previous nonfunctioning
      pituitary adenoma (NFPA). METHODS: From the Dutch National Registry of Growth
      Hormone Treatment in Adults, a nationwide surveillance study in severe GHD
      adults, all patients using >=30 days of GH replacement therapy with previous NFPA
      (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient
      characteristics, fractures and potential influencing factors were investigated.
      RESULTS: At baseline, patients with previous CD were younger, more often female
      and had more often a history of osteopenia or osteoporosis, whereas patients with
      previous acromegaly had more often received cranial radiotherapy and a longer
      duration between treatment of their pituitary tumor and start of adult GH
      replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of
      all patients. Compared to patients with previous NFPA, only patients with
      previous acromegaly had an increased fracture risk after 6 years of GH
      replacement therapy. CONCLUSIONS: During GH replacement therapy, an increased
      fracture risk was observed in severe GHD adult patients previously treated for
      acromegaly, but not in those previously treated for CD, compared to severe GHD
      adult patients using GH replacement therapy because of previous NFPA. Further
      studies are needed to confirm these findings and to elucidate potential
      underlying mechanisms.

PMID- 27048485
TI  - Development of an Enhanced Phenotypic Screen of Cytotoxic T-Lymphocyte Lytic
      Granule Exocytosis Suitable for Use with Synthetic Compound and Natural Product
      Collections.
AB  - We previously developed an assay of cytotoxic T-lymphocyte lytic granule
      exocytosis based on externalization of LAMP-1/CD107A using nonphysiological
      stimuli to generate maximal levels of exocytosis. Here, we used polystyrene beads
      coated with anti-CD3 antibodies to stimulate cells. Light scatter let us
      distinguish cells that contacted beads from cells that had not, allowing
      comparison of signaling events and exocytosis from stimulated and unstimulated
      cells in one sample. Bead stimulation resulted in submaximal exocytosis, making
      it possible to detect compounds that either augment or inhibit lytic granule
      exocytosis. Coupled with the assay's ability to distinguish responses in cells
      that have and have not contacted a stimulatory bead, it is possible to detect
      three kinds of compounds: inhibitors, stimulators, which cause exocytosis, and
      augmenters, which enhance receptor-stimulated exocytosis. To validate the assay,
      we screened a set of synthetic compounds identified using our previous assay and
      a library of 320 extracts prepared from tunicate-associated bacteria. One of the
      extracts augmented exocytosis threefold. Activity-guided fractionation and
      structure elucidation revealed that this compound is the known PKC activator
      teleocidin A-1. We conclude that our modified assay is suitable for screening
      synthetic compound plates and natural product collections, and will be useful for
      identifying immunologically active small molecules. 

PMID- 27048486
TI  - Combined Endoscopic-Radiological Rendezvous for Distal Tail Postoperative
      Pancreatic Fistula (POPF).
AB  - Postoperative pancreatic fistula (POPF) with leakage of pancreatic juice is a
      rare, severe complication following pancreatic resection or, less commonly,
      splenectomy. Definitive treatment can require multidisciplinary approaches. We
      report a case of stenosis of the main pancreatic duct with distal tail GRADE C
      POPF, occurred after splenectomy for Hodgkin lymphoma, successfully treated with
      combined radiological-endoscopic approach. 

PMID- 27048487
TI  - 18F-FDOPA PET/CT-Guided Radiofrequency Ablation of Liver Metastases from
      Neuroendocrine Tumours: Technical Note on a Preliminary Experience.
AB  - AIM: To review our preliminary experience with 6-L-18F
      fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT-guided radiofrequency ablation
      (RFA) of liver metastases from neuroendocrine tumours (NETs). MATERIALS AND
      METHODS: Three patients (mean age 51.3 years; range 43-56) with gastro-entero
      pancreatic NET (GEP-NET) liver metastases underwent 18F-FDOPA PET/CT-guided RFA.
      Patients were referred with oligometastatic hepatic-confined disease (1-6
      metastases; <3 cm) on 18F-FDOPA PET/CT; poor lesion visualisation on US, CT, and
      MR; and ongoing symptoms. Procedures were performed in an interventional PET/CT
      scanner under general anaesthesia using a split-dose protocol. Lesion
      characteristics, procedural duration and technical success (accurate probe
      placement and post-procedural ablation-zone photopaenia), complications, patient
      and operator dose, and clinical outcomes were evaluated. RESULTS: Thirteen liver
      metastases (mean size 11.4 mm, range 8-16) were treated in three patients (two
      presented with "carcinoid syndrome"). Technical success was 100 % with a mean
      procedural duration of 173.3 min (range 90-210) and no immediate complications.
      Mean patient dose was 2844 mGy.cm (range 2104-3686). Operator and radiographer
      doses were acceptable other than the operator's right hand in the first case (149
      uSv); this normalised in the second case. There was no local tumour or extra
      hepatic disease progression at mid-term follow-up (mean 12.6 months; range 6-20);
      however, two cases progressed with new liver metastases at different sites. There
      was 100 % clinical success (n = 2) in resolving carcinoid syndrome symptoms.
      CONCLUSION: 18F-FDOPA PET/CT-guided RFA appears technically feasible, safe, and
      effective in patients with GEP-NETs and low-burden hepatic metastases. Further
      prospective studies are required to elucidate its precise role in tailored
      multimodality management of GEP-NET liver metastases.

PMID- 27048488
TI  - Percutaneous CT and Fluoroscopy-Guided Screw Fixation of Pathological Fractures
      in the Shoulder Girdle: Technical Report of 3 Cases.
AB  - OBJECTIVE: To review our initial experience with percutaneous CT and fluoroscopy
      guided screw fixation of pathological shoulder-girdle fractures. MATERIALS AND
      METHODS: Between May 2014 and June 2015, three consecutive oncologic patients
      (mean age 65 years; range 57-75 years) with symptomatic pathological shoulder
      girdle fractures unsuitable for surgery and radiotherapy underwent percutaneous
      image-guided screw fixation. Fractures occurred through metastases (n = 2) or a
      post-ablation cavity (n = 1). Mechanical properties of osteosynthesis were
      adjudged superior to stand-alone cementoplasty in each case. Cannulated screws
      were placed under combined CT and fluoroscopic guidance with complementary
      radiofrequency ablation or cementoplasty to optimise local palliation and secure
      screw fixation, respectively, in two cases. Follow-up was undertaken every few
      weeks until mortality or most recent appointment. RESULTS: Four pathological
      fractures were treated in three patients (2 acromion, 1 clavicular, 1 coracoid).
      Mean size of associated lesion was 2.6 cm (range 1-4.5 cm). Technical success was
      achieved in all cases (100 %), without complications. Good palliation and
      restoration of mobility were observed in two cases at 2-3 months; one case could
      not be followed due to early post-procedural oncologic mortality. CONCLUSION:
      Percutaneous image-guided shoulder-girdle osteosynthesis appears technically
      feasible with good short-term efficacy in this complex patient subset. Further
      studies are warranted to confirm these promising initial results.

PMID- 27048489
TI  - Traumatic Pseudoaneurysm of the Inferior Mesenteric Artery Branch: A Rare Cause
      of Lower GI Bleeding and Treatment with Selective Coil Embolization.

PMID- 27048490
TI  - N,N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by
      recruiting regulatory T cells through PI3K/Akt pathway in mice.
AB  - N,N-dimethylsphingosine (DMS) has been documented to be in vitro protective
      against myocardial ischemia-reperfusion injury (IRI) and can recruit
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which may participate in the
      cardioprotection. We hypothesized that when in vivo applied after a myocardial
      ischemia, DMS may be cardioprotective by recruiting Tregs. Myocardial IRI was
      induced in C57BL/6 mice by occluding the left main coronary arteries followed by
      relaxation, and DMS (0.43 mg/kg) was intravenously injected 5 min after the onset
      of ischemia. We found that in wild-type (WT) mice, compared with the ischemia
      reperfusion group, DMS reduced the infarct size (47.1 +/- 8.9 vs. 33.1 +/- 3.4 %,
      p < 0.01), and neutrophil infiltration at 24 h reperfusion (R) evaluated by TTC
      and immunohistochemical staining, respectively, and increased the aggregation of
      Tregs [(6 +/- 1)/mm(2) vs. (30 +/- 4)/mm(2), p < 0.01], peaking at 1 h R by
      immunofluorescence staining, with reduced gene expression of inflammatory factors
      at 4 h R in the reperfused myocardium by real-time PCR. This protection was
      abolished by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor or Tregs
      depleting antibody. Relative to WT mice, the cardioprotection conferred by T cell
      and B cell- deficient Rag2 knockout (KO) mice was not strengthened by DMS or by
      DMS and the adoptive transfer of Tregs from WT mice, but was abolished by DMS and
      WT non-Tregs and was recaptured by the cotransfer with WT Tregs but not with
      Akt1(+/-) mice-derived Tregs. In conclusion, applied at an early stage of
      ischemia, DMS may be in vivo protective against myocardial IRI by recruiting
      Tregs via PI3K/Akt pathway.

PMID- 27048491
TI  - Dissipation kinetics, safety evaluation, and preharvest interval assessment of
      trichlorfon application on rice.
AB  - Nowadays, there is an urgent need for the investigation of the field dissipation
      and assessment of the preharvest interval for trichlorfon residues on rice. To
      protect consumers from potential health risks, this study can provide references
      for the safe application of trichlorfon in the rice fields. Results of the field
      dissipation study showed that the dissipation dynamic equations of trichlorfon
      were based on the first-order reaction dynamic equations and that the dissipation
      rates vary among rice plant, brown rice, rice bran, soil, and water. The 2-year
      field trials conducted in Yangzhou and Xiaogan suggested the interval of each
      application for trichlorfon on rice to be at least 7 days when 80 % trichlorfon
      SP was sprayed with a dose ranges between 80 and 160 a.i g/667 m(2).
      Additionally, the preharvest interval of the last application should be at least
      15 days to ensure the amounts of residues below the maximum residue limits of
      trichlorfon on brown rice (0.1 mg/kg).

PMID- 27048492
TI  - Gaseous pollutants from brick kiln industry decreased the growth, photosynthesis,
      and yield of wheat (Triticum aestivum L.).
AB  - Gaseous pollutant emissions from brick kiln industries deteriorate the current
      state of ambient air quality in Pakistan and worldwide. These gaseous pollutants
      affect the health of plants and may decrease plant growth and yield. A field
      experiment that was conducted to monitor the concentration of gaseous pollutants
      emitted mainly from brick kilns in the ambient air and associated impacts on the
      growth and physiological attributes of the two wheat (Triticum spp.) cultivars.
      Plants were grown at three sites, including control (Ayub Agriculture Research
      Institute, AARI), low pollution (LP) site (Small Estate Industry), and high
      pollution (HP) site (Sidar Bypass), of Faisalabad, Pakistan. Monitoring of
      ambient air pollution at experimental sites was carried out using the state-of
      art ambient air analyzers. Plants were harvested after 120 days of germination
      and were analyzed for different growth attributes. Results showed that the hourly
      average concentration of gaseous air pollutants CO, NO2, SO2, and PM10 at HP site
      were significantly higher than the LP and control sites. Similarly, gaseous
      pollutants decreased plant height, straw and grain yield, photosynthesis and
      increased physical injury, and metal concentrations in the grains. However, wheat
      response toward gaseous pollutants did not differ between cultivars (Galaxy and
      8173) studied. Overall, the results indicated that brick kiln emissions could
      reduce the performance of wheat grown in the soils around kilns and confirm the
      adverse impacts of pollutants on the growth, yield, and quality of the wheat.

PMID- 27048493
TI  - Investigating chlorophyll and nitrogen levels of mangroves at Al-Khor, Qatar: an
      integrated chemical analysis and remote sensing approach.
AB  - Mangroves are unique ecosystems that dominate tropical and subtropical coastlines
      around the world. They provide shelter and nursery to wide variety of species
      such as fish and birds. Around 73 species of mangroves were recognized around the
      world. In Qatar, there is only one mangrove species Avicennia marina that is
      predominant along the northeastern coast. Assessing the health of these valuable
      ecosystems is vital for protection, management, and conservation of those
      resources. In this study, an integrated approach of chemical and remote sensing
      analysis was implemented to investigate the current status of the mangrove trees
      in Al-Khor, Qatar. Fifteen different A. marina trees from different locations in
      the mangrove forest were examined for their chlorophyll and nitrogen content
      levels. Soil analysis was also conducted to understand the effect of moisture on
      nitrogen availability. Results shows that currently, mangroves are in a good
      status in terms of nitrogen availability and chlorophyll levels which are related
      and both are key factors for photosynthesis. Remote sensing techniques were used
      for chlorophyll prediction. The results showed that these methods have the
      potential to be used for chlorophyll prediction and estimation. 

PMID- 27048494
TI  - US drug makers have imposed big price rises for top selling drugs, study finds.

PMID- 27048495
TI  - Assessment of the psychometrics of a PROMIS item bank: self-efficacy for managing
      daily activities.
AB  - PURPOSE: The aim of this study is to investigate the psychometrics of the Patient
      Reported Outcomes Measurement Information System self-efficacy for managing daily
      activities item bank. METHODS: The item pool was field tested on a sample of 1087
      participants via internet (n = 250) and in-clinic (n = 837) surveys. All
      participants reported having at least one chronic health condition. The 35 item
      pool was investigated for dimensionality (confirmatory factor analyses, CFA and
      exploratory factor analysis, EFA), item-total correlations, local independence,
      precision, and differential item functioning (DIF) across gender, race,
      ethnicity, age groups, data collection modes, and neurological chronic conditions
      (McFadden Pseudo R (2) less than 10 %). RESULTS: The item pool met two of the
      four CFA fit criteria (CFI = 0.952 and SRMR = 0.07). EFA analysis found a
      dominant first factor (eigenvalue = 24.34) and the ratio of first to second
      eigenvalue was 12.4. The item pool demonstrated good item-total correlations
      (0.59-0.85) and acceptable internal consistency (Cronbach's alpha = 0.97). The
      item pool maintained its precision (reliability over 0.90) across a wide range of
      theta (3.70), and there was no significant DIF. CONCLUSION: The findings
      indicated the item pool has sound psychometric properties and the test items are
      eligible for development of computerized adaptive testing and short forms.

PMID- 27048496
TI  - Assessing health-related quality of life in patients with breast cancer: a
      systematic and standardized comparison of available instruments using the EMPRO
      tool.
AB  - PURPOSE: The objective was to obtain a standardized evaluation of available
      specific and generic breast cancer health-related quality-of-life instruments.
      METHODS: We carried out systematic literature reviews in the PubMed and EMBASE
      databases to identify manuscripts which contained information regarding either
      the development process or metric properties of health-related quality-of-life
      instruments used among breast cancer patients. Each instrument was evaluated
      independently by two researchers, and occasionally a third one, using the
      Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall score
      and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to
      best): concept and measurement model, reliability, validity, responsiveness,
      interpretability, burden, and alternative forms. RESULTS: FACT-B was the
      instrument with the best global performance, obtaining an overall EMPRO score of
      79.27. It was also the most accurate instrument on the Concept and Measurement
      Model, Reliability, and Interpretability attributes. Four more instruments scored
      over 50 points on the overall score, which summarizes the five attribute-specific
      scores: EORTC BR-23, IBCSG, WHO-QOL BREF, and SF-36. An overall score of at least
      50 points implies that the use of these instruments could be recommended for
      assessing health-related quality of life in breast cancer patients. CONCLUSION:
      The FACT-B scored the highest on overall on our EMPRO evaluation of instruments
      measuring health-related quality of life among breast cancer patients. However,
      depending on the purpose of the study, several instruments (EORTC BR-23, IBCSG,
      SF-36, and WHO-QOL BREF) have shown good performance in some of the specific
      individual dimensions included in the EMPRO.

PMID- 27048497
TI  - Predictors of health-related quality of life in people with a complex chronic
      disease including multimorbidity: a longitudinal cohort study.
AB  - PURPOSE: Factors that predict the health-related quality of life (HRQoL) of
      people with complex chronic diseases have not been investigated to date.
      Determining the impact of disease on daily activities is a factor that is
      particularly important with this group of people. This study examined the
      influence of a range of predictors (including the impact of chronic diseases on
      daily activities), on HRQoL in patients with complex chronic diseases over a 12
      month period. METHOD: A longitudinal cohort study was conducted with outcomes
      measured at baseline, 3, 6 and 12 months post-baseline. Adults attending an
      Australian community-based rehabilitation service were included. HRQoL was
      measured using the SF-36 and corresponding preference-based health utility.
      Predictor variables included sociodemographic factors, disease factors (e.g.
      impact of diseases on daily activities), intervention factors, psychosocial
      factors and HRQoL components that were not included as the dependent variable.
      Linear mixed-effects regression was used to examine the relationship between
      predictor variables and HRQoL. RESULTS: Data from 351 participants were included.
      The impact of chronic disease on daily activities was the most frequent
      significant predictor of HRQoL outcomes. Other significant predictors included
      the impact of chronic back pain or sciatica on daily activities, the number of
      comorbidities, general health functioning and psychological distress. CONCLUSION:
      Models of health care for people with complex chronic disease may be enhanced by
      greater focus on patients' daily activities during assessment and intervention
      delivery. The range of significant predictors highlights the importance of an
      interdisciplinary team for managing complex chronic disease or targeted
      intervention strategies.

PMID- 27048498
TI  - Eating disorder features and quality of life: Does gender matter?
AB  - PURPOSE: This study examined whether gender moderates the associations between
      eating disorder features and quality-of-life impairment and whether eating
      disorder features can explain gender differences in quality of life in a sample
      of undergraduate students. METHODS: The SF-12 Physical and Mental Component
      Summary Scales were used to measure health-related quality of life (HRQoL), and
      the Eating Disorders Examination Questionnaire (EDE-Q) was used to quantify
      eating disorder behaviors and cognitions. These self-report forms were completed
      by undergraduate men and women (n = 709). RESULTS: Gender was a significant
      predictor of mental HRQoL, such that women in this sample reported poorer mental
      HRQoL than men. Eating disorder cognitions were the strongest predictor of
      undergraduate students' mental and physical HRQoL, while binge eating negatively
      predicted their physical HRQoL only. Gender was not found to moderate the
      associations between eating disorder features and HRQoL, and eating disorder
      cognitions were found to mediate the association between gender and mental HRQoL
      such that a proportion of the difference between undergraduate men and women's
      mental HRQoL was attributable to eating disorder cognitions. CONCLUSION: This
      study provided further evidence of the significant impact of eating disorder
      features, particularly eating disorder cognitions, on HRQoL. The finding that
      gender did not moderate the relationships between eating disorder features and
      HRQoL indicates the importance of investigating these features in both men and
      women in future research.

PMID- 27048499
TI  - Changes in well-being after myocardial infarction: Does coping matter?
AB  - PURPOSE: This study explores changes in emotional component of subjective well
      being (SWB) of patients after their first myocardial infarction (MI) and two
      kinds of mechanisms: attribution of positive (PA) and negative (NA) affect and a
      mediation effect of coping. METHODS: Affect and coping strategies (problem-,
      emotion-, and avoidance-focused) were assessed in 121 male patients (age 52.26 +/
      7.08 years) a few days after the first MI and then 1 and 6 months later. The
      indicator of emotional SWB was affect balance, calculated as the ratio of PA to
      NA. Mediation was tested using the PROCESS macro. RESULTS: The affect balance
      changed over time, from a predominance of negativity a few days post-MI to more
      positive 1 and 6 months later (F 2, 119 = 21.87, p < 0.001). The results of
      parallel multiple mediation showed a mediating effect of emotion-focused coping
      on the changes in affect balance over time. Separate analyses for PA and NA
      showed the same results for NA. Problem-focused coping mediated PA changes in the
      early post-hospitalization period. CONCLUSIONS: Myocardial infarction may
      activate PA alongside the NA, but the predominance of PA over NA in both early
      and late post-hospitalization period was minimal. Affect balance appeared to be
      largely dependent on NA and its changes. Coping strategies partly mediated the
      changes in well-being, providing a basis for practical interventions.

PMID- 27048500
TI  - The effects of HIV self-testing on the uptake of HIV testing and linkage to
      antiretroviral treatment among adults in Africa: a systematic review protocol.
AB  - BACKGROUND: HIV is still a global public health problem. More than 75 % of HIV
      infected people are in Africa, and most of them are unaware of their HIV status,
      which is a barrier to accessing antiretroviral treatment. Our review aims,
      firstly, to determine whether HIV self-testing is an effective method to increase
      the uptake of testing, the yield of new HIV-positive diagnoses, and the linkage
      to antiretroviral treatment. Secondly, we aim to review the factors that
      facilitate or impede the uptake of HIV self-testing. METHODS/DESIGN: Participants
      will be adults living in Africa. For the first aim, the intervention will be HIV
      self-testing either alone or in addition to HIV testing standard of care. The
      comparison will be HIV testing standard of care. The primary outcomes will be (i)
      uptake of HIV testing and (ii) yield of new HIV-positive diagnoses. The secondary
      outcomes will be (a) linkage to antiretroviral (ARV) treatment and (b) incidence
      of social harms. For the second aim, we will review barriers and facilitators to
      the uptake of self-testing. We will search PubMed, Cochrane Central Register of
      Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide, and CINAHL for
      eligible studies from 1998, with no language limits. We will check reference
      lists of included studies for other eligible reports. Eligible studies will
      include experimental and observational studies. Two authors will independently
      screen the search output, select studies, and extract data, resolving
      discrepancies by consensus and discussion. Two authors will use Cochrane risk of
      bias tools for experimental studies, the Newcastle-Ottawa Quality Assessment
      Scale for observational studies, and the Critical Appraisal Skills Programme
      (CASP) quality assessment tool for qualitative studies. DISCUSSION: Innovative
      and cost-effective community-based HIV testing strategies, such as self-testing,
      will contribute to universal coverage of HIV testing in Africa. The findings from
      this systematic review will guide development of self-testing policy in African
      countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023935.

PMID- 27048501
TI  - Is protease inhibitors based antiretroviral therapy during pregnancy associated
      with an increased risk of preterm birth? Systematic review and a meta-analysis.
AB  - BACKGROUND: Antiretroviral therapy is recommended during pregnancy to decrease
      the risk of perinatal transmission of HIV-1 infection and to improve maternal
      health. However, some studies have reported that antiretroviral treatment (ART)
      containing protease inhibitors (PI) is associated with an increased risk of
      preterm birth. In contrast, other studies have reported no increased risk. This
      meta-analysis was conducted to derive a more reliable estimate of the association
      between the prenatal use of PI based ART regimen and preterm birth. METHODS: A
      systemic review and meta-analysis was conducted using published studies which
      were identified through a computerized search using the Medline/PubMed database,
      Google Scholar and Health Inter Network Access to Research Initiative (HINARI).
      The analysis was undertaken using STATA version 11.0 software and studies were
      described by forest plot. Heterogeneity across studies was checked using Cochran
      Q test and I2 test. An adjusted odd ratio with 95% confidence intervals [95% CI]
      was pooled using a random effects model. RESULTS: The Cochrane Q test (Q test p =
      0.051) showed a good homogeneity among studies. However, medium heterogeneity was
      observed in up to 46% of the sample using the I2 test (I2 = 46.5%). The Egger
      weighted regression method (p = 0.04) showed evidence of publication bias, but
      Begg rank correlation statistics (p = 0.47) did not show evidence of publication
      bias. The pooled analysis of 10 studies showed that protease based ART exposure
      during pregnancy was associated with an increased risk of preterm birth (pooled
      odds ratio 1.32 (95% CI, 1.04 to 1.59). CONCLUSIONS: This meta-analysis revealed
      that the PI based ART exposure during pregnancy is significantly associated with
      an increased risk of preterm birth. There should be strong cautions against
      initiating ART during pregnancy and PI based ARV should be replaced by others
      drug regime. Protease inhibitor ART drugs should not be included as part of
      therapy during pregnancy.

PMID- 27048502
TI  - Gastrointestinal mucosal barrier function and diseases.
AB  - The gastrointestinal mucosal barrier plays an essential role in the separation of
      the inside of the body from the outside environment. Tight junctions (TJs) are
      the most important component for construction of a constitutive barrier of
      epithelial cells, and they regulate the permeability of the barrier by tightly
      sealing the cell-cell junctions. TJ proteins are represented by claudins,
      occludin, junctional adhesion molecules, and scaffold protein zonula occludens.
      Among these TJ proteins, claudins are the major components of TJs and are
      responsible for the barrier and the polarity of the epithelial cells.
      Gastrointestinal diseases including reflux esophagitis, inflammatory bowel
      disease, functional gastrointestinal disorders, and cancers may be regulated by
      these molecules, and disruption of their functions leads to chronic inflammatory
      conditions and chronic or progressive disease. Therefore, regulation of the
      barrier function of epithelial cells by regulating the expression and
      localization of TJ proteins is a potential new target for the treatment of these
      diseases. Treatment strategies for these diseases might thus be largely altered
      if symptom generation and/or immune dysfunction could be regulated through
      improvement of mucosal barrier function. Since TJ proteins may also modify tumor
      infiltration and metastasis, other important goals include finding a good TJ
      biomarker of cancer progression and patient prognosis, and developing TJ protein
      targeted therapies that can modify patient prognosis. This review summarizes
      current understanding of gastrointestinal barrier function, TJ protein
      expression, and the mechanisms underlying epithelial barrier dysregulation in
      gastrointestinal diseases. 

PMID- 27048503
TI  - The German National Program on Psoriasis Health Care 2005-2015: results and
      experiences.
AB  - In 2005, the first national psoriasis survey in Germany revealed large deficits
      in health care particularly in patients with moderate to severe disease. The
      consecutive goal was to improve health care for psoriasis countrywide. For this,
      a large-scale national program was initiated starting with a comprehensive
      analysis of structures and processes of care for psoriasis. Patient burden,
      economic impact and barriers to care were systematically analyzed. In order to
      optimize routine care, a S3 guideline, a set of outcomes measures and treatment
      goals, were developed. Implementation was enforced by the German Psoriasis
      Networks (PsoNet) connecting the most dedicated dermatologists. The annual
      National Conference on Health Care in Psoriasis established in 2009 consented
      National Health Care Goals in Psoriasis 2010-2015 and defined a set of quality
      indicators, which are monitored on a regular basis. Currently 28 regional
      networks including more than 800 dermatologists are active. Between 2005 and 2014
      7 out of 8 quality indicators have markedly improved, and regional disparities
      were resolved. e.g., mean PASI (Psoriasis Area Severity Index) dropped from 11.4
      to 8.1 and DLQI (Dermatology Life Quality Index) from 8.6 to 5.9. A decade of
      experience indicates that a coordinated nationwide psoriasis program based on
      goal orientation can contribute to better quality of care and optimized outcomes.

PMID- 27048504
TI  - Short- and long-term psychosocial of a single episode of alcoholic intoxication:
      a cohort study among Dutch adolescents.
AB  - The short- and long-term psychological consequences of a single episode of
      alcohol intoxication in adolescents are unknown. Twenty-four adolescents (12 M,
      12 F), mean age 18.3 +/- 1.1 years, who had been admitted to the pediatric ward
      with alcohol intoxication (mean age at admission 15.6 +/- 1.1) and thirty-two
      parents were interviewed on the intoxication episode and the subsequent
      consequences. This interview took place 2-3 years after the alcohol intoxication.
      At the same time, all participants completed questionnaires, assessing general
      and demographic information, detailed information about current alcohol use,
      present-day health-related quality of life, and psychological well-being. We
      observed that short-term (<6 months) psychosocial consequences on family life,
      family rules, friendships, and school were retrospectively judged more neutral
      and even more positive than negative by adolescents and their parents. Eighty-six
      percent of all reported changes by adolescents and parents, directly after the
      intoxication, lasted 6 months or less. At follow-up present-day quality of life
      was comparable to the norm, social functioning was significantly better and their
      mental health proved to be within the normal range (no emotional and behavioral
      problems). Since the intoxication, none of the participants had dropped out of
      school and their present-day alcohol use was comparable to estimated averages for
      their age. CONCLUSION: Short- and long-term psychosocial consequences of a single
      episode of alcohol intoxication were positively judged by adolescents and their
      parents. WHAT IS KNOWN: * Alcohol abuse among adolescents is a growing concern
      both in society and pediatrics. What is new: * This manuscript describes short
      and long term psychological consequences of a single episode of alcohol
      intoxication in adolescents.

PMID- 27048505
TI  - MicroRNA-143 inhibits IL-13-induced dysregulation of the epidermal barrier
      related proteins in skin keratinocytes via targeting to IL-13Ralpha1.
AB  - Atopic dermatitis is a chronic inflammatory skin disease characterized by the
      dysregulation of the epidermal barrier and the immune system. Interleukin (IL)
      13, a key T helper 2 cytokine, has been shown to impair the epidermal barrier
      function via downregulating epidermal barrier proteins. MicroRNAs are small
      noncoding RNAs of approximately 22 nucleotides that act as negative regulators of
      gene expression at posttranscriptional levels. MicroRNA-143 is known to be a
      tumor suppressor in various tumors; however, its role in the regulation of
      allergic diseases including atopic dermatitis remains elusive. In this study, we
      investigated whether IL-13Ralpha1 was a microRNA-143 target to regulate the
      effects of IL-13 on epidermal barrier function. After the stimulation of IL-13 in
      human epidermal keratinocytes, the level of microRNA-143 was decreased. The
      luciferase activity of the vector containing 3'UTR of IL-13Ralpha1 was decreased
      in keratinocytes transfected with microRNA-143 mimic compared to those of the
      corresponding controls. The forced expression of microRNA-143 mimic blocked the
      IL-13-induced downregulation of filaggrin, loricrin, and involucrin in epidermal
      keratinocytes. Collectively, these data suggest that microRNA-143 suppresses IL
      13 activity and inflammation through targeting of IL-13Ralpha1 in epidermal
      keratinocytes. MicroRNA-143 may serve as a potential preventive and therapeutic
      target in atopic dermatitis. 

PMID- 27048506
TI  - Phenotype and genotype in patients with Larsen syndrome: clinical homogeneity and
      allelic heterogeneity in seven patients.
AB  - BACKGROUND: Larsen syndrome is an autosomal dominant skeletal dysplasia
      characterized by large joint dislocations and craniofacial dysmorphism. It is
      caused by missense or small in-frame deletions in the FLNB gene. To further
      characterize the phenotype and the mutation spectrum of this condition, we
      investigated seven probands, five sporadic individuals and a mother-son-duo with
      Larsen syndrome. METHODS: The seven patients from six unrelated families were
      clinically and radiologically evaluated. All patients were screened for mutations
      in selected exons and exon-intron boundaries of the FLNB gene by Sanger
      sequencing. FLNB transcript analysis was carried out in one patient to analyse
      the effect of the sequence variant on pre-mRNA splicing. RESULTS: All patients
      exhibited typical facial features and joint dislocations. Contrary to the widely
      described advanced carpal ossification, we noted delay in two patients. We
      identified the five novel mutations c.4927G  A/p.(Gly1643Ser), c.4876G > T /
      p.(Gly1626Trp), c.4664G > A / p.(Gly1555Asp), c.2055G > C / p.Gln685delins10 and
      c.5021C > T / p.(Ala1674Val) as well as a frequently observed mutation in Larsen
      syndrome [c.5164G > A/p.(Gly1722Ser)] in the hotspot regions. FLNB transcript
      analysis of the c.2055G > C variant revealed insertion of 27 bp intronic sequence
      between exon 13 and 14 which gives rise to in-frame deletion of glutamine 685 and
      insertion of ten novel amino acid residues (p.Gln685delins10). CONCLUSIONS: All
      seven individuals with Larsen syndrome had a uniform clinical phenotype except
      for delayed carpal ossification in two of them. Our study reveals five novel FLNB
      mutations and confirms immunoglobulin-like (Ig) repeats 14 and 15 as major
      hotspot regions. The p.Gln685delins10 mutation is the first Larsen syndrome
      associated alteration located in Ig repeat 5. All mutations reported so far leave
      the filamin B protein intact in accordance with a gain-of-function effect. Our
      findings underscore the characteristic clinical picture of FLNB-associated Larsen
      syndrome and add Ig repeat 5 to the filamin B domains affected by the clustered
      mutations.

PMID- 27048507
TI  - Risk factors for cognitive decline associated with gait speed in community
      dwelling elderly Koreans with MMSE scores of 30.
AB  - BACKGROUND AND AIM: We aimed to investigate the association between lower gait
      speed and cognitive decline over a 3-year period in community-dwelling older
      people with mini-mental state examination (MMSE) scores of 30 at baseline.
      METHODS: The study was based on data from 10,003 Koreans aged 60 years or older
      who completed the National Elderly Survey in both 2008 and 2011. Among them 620
      subjects achieved MMSE scores of 30 in 2008. Over a 3-year period, preservation
      of MMSE score 28 or more was defined as preserved cognition and decrease of three
      or more points as cognitive decline. A 4-m gait speed was measured at baseline.
      Data on sociodemographic factors (age, number of schooling years, and household
      composition), alcohol drinking, current smokers, Korean version of Short form
      Geriatric Depression Scale score, and self-reported comorbid conditions, were
      collected. RESULTS: Of 620 (weighted 884) respondents included in the analysis,
      208 (52.3 %) of 398 males (weighted 567) and 152 (68.5 %) of 222 females
      (weighted 317) suffered cognitive decline over the 3-year period. After
      adjustment, lower gait speed was associated with cognitive decline in males (OR
      2.29; 95 % CI 1.07-4.89, P = 0.032). Educational level was a significant risk
      factor for both men and women (OR 0.86; 95 % CI 0.79-0.93 in males, OR 0.75; 95 %
      CI 0.65-0.87 in females). Males diagnosed with hypertension (OR 0.44; 95 % CI
      0.22-0.88) or male smokers (OR 0.38; 95 % CI 0.19-0.75) were significantly less
      likely to have cognitive decline. There was no significant association between
      cognitive decline and gait speed in females. CONCLUSIONS: Higher 4-m gait speed
      is associated with preservation of cognitive function over time in men, but not
      in women.

PMID- 27048508
TI  - Diagnosing sepsis is subjective and highly variable: a survey of intensivists
      using case vignettes.
AB  - BACKGROUND: Sepsis is the focus of national quality improvement programs and a
      recent public reporting measure from the Centers for Medicare and Medicaid
      Services. However, diagnosing sepsis requires interpreting nonspecific signs and
      can therefore be subjective. We sought to quantify interobserver variability in
      diagnosing sepsis. METHODS: We distributed five case vignettes of patients with
      suspected or confirmed infection and organ dysfunction to a sample of practicing
      intensivists. Respondents classified cases as systemic inflammatory response
      syndrome, sepsis, severe sepsis, septic shock, or none of the above.
      Interobserver variability was calculated using Fleiss' kappa for the five-level
      classification, and for answers dichotomized as severe sepsis/septic shock versus
      not-severe sepsis/septic shock and any sepsis category (sepsis, severe sepsis, or
      septic shock) versus not-sepsis. RESULTS: Ninety-four physicians completed the
      survey. Most respondents (88%) identified as critical care specialists; other
      specialties included pulmonology (39%), anesthesia (19%), surgery (9%), and
      emergency medicine (9%). Respondents had been in practice for a median of 8
      years, and 90% practiced at academic hospitals. Almost all respondents (83%) felt
      strongly or somewhat confident in their ability to apply the traditional
      consensus sepsis definitions. However, overall interrater agreement in sepsis
      diagnoses was poor (Fleiss' kappa 0.29). When responses were dichotomized into
      severe sepsis/septic shock versus not-severe sepsis/septic shock or any sepsis
      category versus not-sepsis, agreement was still poor (Fleiss' kappa 0.23 and
      0.18, respectively). Seventeen percent of respondents classified one of the five
      cases as severe sepsis/septic shock, 27.7% rated two cases, 33.0% respondents
      rated three cases, 19.2% rated four cases, and 3.2% rated all five cases as
      severe sepsis/septic shock. Among respondents who felt strongly confident in
      their ability to use sepsis definitions (n = 45), agreement was no better
      (Fleiss' kappa 0.28 for the five-category classification, and Fleiss' kappa 0.21
      for the dichotomized severe sepsis/septic shock classification). Cases were felt
      to be extremely or very realistic in 74% of responses; only 3% were deemed
      unrealistic. CONCLUSIONS: Diagnosing sepsis is extremely subjective and variable.
      Objective criteria and standardized methodology are needed to enhance consistency
      and comparability in sepsis research, surveillance, benchmarking, and reporting.

PMID- 27048509
TI  - Isolated single umbilical artery is an independent risk factor for perinatal
      mortality and adverse outcomes in term neonates.
AB  - OBJECTIVE: To determine whether an isolated single umbilical artery (iSUA) is an
      independent risk factor for perinatal mortality in term neonates with normal
      estimated fetal weight (EFW) prior to delivery. METHOD: A population-based study
      was conducted, including all deliveries occurring between 1993 and 2013, in a
      tertiary medical center. Pregnancies with and without iSUA were compared.
      Multiple gestations, chromosomal, and structural abnormalities were excluded from
      the cohort. Only pregnancies delivered at term with normal EFW evaluated prior to
      delivery were included. Stratified analysis was performed using multiple logistic
      regression models to evaluate the risk of adverse outcomes and perinatal
      mortality for iSUA fetuses. RESULTS: During the study period, 233,123 deliveries
      occurred at "Soroka" University Medical Center, out of which 786 (0.3 %) were
      diagnosed with iSUA. Different pregnancy complications were more common with iSUA
      fetuses including: placental abruption (OR = 3.4), true knot of cord (OR = 3.5)
      and cord prolapse (OR = 2.8). Induction of labor and cesarean delivery were also
      more common in these pregnancies (OR = 1.5 and OR = 1.9, respectively). iSUA
      neonates had lower Apgar scores at 1 and 5 min (OR = 1.8, OR = 1.9, respectively)
      compared to the control group and perinatal mortality rates were higher both
      antenatally (IUFD, OR = 8.1) and postnatally (PPD, OR = 6.1). CONCLUSION: iSUA
      appears to be an independent predictor of adverse perinatal outcomes in term
      neonates.

PMID- 27048510
TI  - Phonological similarity in working memory span tasks.
AB  - In a series of four experiments, we explored what conditions are sufficient to
      produce a phonological similarity facilitation effect in working memory span
      tasks. By using the same set of memoranda, but differing the secondary-task
      requirements across experiments, we showed that a phonological similarity
      facilitation effect is dependent upon the semantic relationship between the
      memoranda and the secondary-task stimuli, and is robust to changes in the
      representation, ordering, and pool size of the secondary-task stimuli. These
      findings are consistent with interference accounts of memory (Brown, Neath, &
      Chater, Psychological Review, 114, 539-576, 2007; Oberauer, Lewandowsky, Farrell,
      Jarrold, & Greaves, Psychonomic Bulletin & Review, 19, 779-819, 2012), whereby
      rhyming stimuli provide a form of categorical similarity that allows distractors
      to be excluded from retrieval at recall.

PMID- 27048511
TI  - Tick infestation in birds and prevalence of pathogens in ticks collected from
      different places in Germany.
AB  - The importance of ticks and tick-borne pathogens for human and animal health has
      been increasing over the past decades. For their transportation and
      dissemination, birds may play a more important role than wingless hosts. In this
      study, tick infestation of birds in Germany was examined. Eight hundred ninety
      two captured birds were infested with ticks and belonged to 48 different species,
      of which blackbirds (Turdus merula) and song thrushes (Turdus philomelos) were
      most strongly infested. Ground feeders were more strongly infested than non
      ground feeders, sedentary birds more strongly than migratory birds, and short
      distance migratory birds more strongly than long-distance migratory birds. Mean
      tick infestation per bird ranged between 2 (long-distance migratory bird) and 4.7
      (sedentary bird), in some single cases up to 55 ticks per bird were found. With
      the exception of three nymphs of Haemaphysalis spp., all ticks belonged to Ixodes
      spp., the most frequently detected tick species was Ixodes ricinus. Birds were
      mostly infested by nymphs (65.1 %), followed by larvae (32.96 %). Additionally,
      ticks collected from birds were examined for several pathogens: Tick-borne
      encephalitis virus (TBEV) and Sindbisvirus with real-time RT-PCR, Flaviviruses,
      Simbuviruses and Lyssaviruses with broad-range standard RT-PCR-assays, and
      Borrelia spp. with a Pan-Borrelia real-time PCR. Interestingly, no viral
      pathogens could be detected, but Borrelia spp. positive ticks were collected from
      76 birds. Borrelia (B.) garinii, B. valaisiaina, B. burgdorferi s.s. and B.
      afzelii were determined. The screening of ticks and birds for viral pathogens
      with broad range PCR-assays was tested and the use as an "early warning system"
      is discussed. 

PMID- 27048512
TI  - Neural model of gene regulatory network: a survey on supportive meta-heuristics.
AB  - Gene regulatory network (GRN) is produced as a result of regulatory interactions
      between different genes through their coded proteins in cellular context. Having
      immense importance in disease detection and drug finding, GRN has been modelled
      through various mathematical and computational schemes and reported in survey
      articles. Neural and neuro-fuzzy models have been the focus of attraction in
      bioinformatics. Predominant use of meta-heuristic algorithms in training neural
      models has proved its excellence. Considering these facts, this paper is
      organized to survey neural modelling schemes of GRN and the efficacy of meta
      heuristic algorithms towards parameter learning (i.e. weighting connections)
      within the model. This survey paper renders two different structure-related
      approaches to infer GRN which are global structure approach and substructure
      approach. It also describes two neural modelling schemes, such as artificial
      neural network/recurrent neural network based modelling and neuro-fuzzy
      modelling. The meta-heuristic algorithms applied so far to learn the structure
      and parameters of neutrally modelled GRN have been reviewed here. 

PMID- 27048513
TI  - Approximating the stabilization of cellular metabolism by compartmentalization.
AB  - Biochemical regulation in compartmentalized metabolic networks is highly complex
      and non-intuitive. This is particularly true for cells of higher plants showing
      one of the most compartmentalized cellular structures across all kingdoms of
      life. The interpretation and testable hypothesis generation from experimental
      data on such complex systems is a challenging step in biological research and
      biotechnological applications. While it is known that subcellular compartments
      provide defined reaction spaces within a cell allowing for the tight coordination
      of complex biochemical reaction sequences, its role in the coordination of
      metabolic signals during metabolic reprogramming due to environmental
      fluctuations is less clear. In the present study, we numerically analysed the
      effects of environmental fluctuations in a subcellular metabolic network with
      regard to the stability of an experimentally observed steady state in the genetic
      model plant Arabidopsis thaliana. Applying a method for kinetic parameter
      normalization, several millions of probable enzyme kinetic parameter
      constellations were simulated and evaluated with regard to the stability
      information of the metabolic homeostasis. Information about the stability of the
      metabolic steady state was derived from real parts of eigenvalues of Jacobian
      matrices. Our results provide evidence for a differential stabilizing
      contribution of different subcellular compartments. We could identify stabilizing
      and destabilizing network components which we could classify according to their
      subcellular localization. The findings prove that a highly dynamic interplay
      between intracellular compartments is preliminary for an efficient stabilization
      of a metabolic homeostasis after environmental perturbation. Further, our results
      provide evidence that feedback-inhibition originating from the cytosol and
      plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar
      control. In summary, our results indicate stabilizing and destabilizing network
      components in context of their subcellular organization. 

PMID- 27048514
TI  - How to review a case report.

PMID- 27048516
TI  - Margaret McCartney: A sexist contract for junior doctors.

PMID- 27048515
TI  - Effect of interleukin 6 -174G>C gene polymorphism on opioid requirements after
      total hip replacement.
AB  - OBJECTIVE: In recent years, increasing attention has been paid to the
      contribution of genetic factors to variability in patient pain threshold and the
      efficacy of pain management. One of the genes implicated in pain pathology and
      treatment response is interleukin 6 (IL6). The aim of the present study was to
      evaluate the association between IL6 (rs1800795: -174G>C) and opioid requirements
      in patients after total hip replacement (THR). METHODS: A total of 196 patients
      eligible for the study (126 women, 70 men) were subjected to THR. The THR
      procedure was performed using spinal anaesthesia after implementing routine peri
      operative monitoring. After the procedure each patient was individually observed,
      and the patient-specific chart of dynamic changes in pain perception was
      recorded, using the five-level Verbal Rating Scale (VRS). The multimodal
      analgesic treatment after THR was defined by the operating surgeons after
      considering indications and contraindications to the use of different groups of
      drugs (opioid and non-opioid analgesics). Postoperative pain was controlled by
      the patient-controlled analgesia method and VRS during the day-time, as well as
      night-time nurse-controlled analgesia. All medication adjustments were recorded
      in the individual patient files. In the case of moderate pain intensity (VRS
      assessed), a patient was administered the non-opioid analgesic drug, and for high
      intensity pain the opioid. The analysis of pain relief therapy included
      information on the drugs applied, mode of dosing (single or multiple), daily
      dose, route of administration, and drug refusal due to the absence of pain
      recorded each study day, i.e. on the day of surgery and recovery in the
      postoperative room (day 0), and then daily from day 1 to day 6. Polymorphism
      rs1800795:G>C in the promoter region of the IL6 gene (-174G>C) was determined
      using the PCR-RFLP method. RESULTS: The patients carrying at least one IL6 -174G
      allele (GG homozygote and GC heterozygote) were administered opioids
      significantly more often on days 0 (p = 0.0029), 3 (p = 0.019) and 4 (p = 0.031)
      after surgery compared with CC homozygous patients. Those patients also required
      a significantly higher opioid dose on days 3 (p = 0.029) and 4 (p = 0.030).
      Multivariate analysis demonstrated that the presence of the -174G allele was an
      independent factor predisposing patients to the administration of opioids during
      the first 24 h [p = 0.001, odds ratio (OR) 7.1, 95 % confidence interval (CI)
      2.17-22.7], on day 3 (p = 0.01, OR 2.79, 95 % CI 1.25-6.26) and day 4 (p = 0.01,
      OR = 2.61, 95 % CI 1.17-5.79). CONCLUSION: The presence of the G allele IL6 gene
      (-174G>C) polymorphism was found to be an independent factor predisposing to a
      higher dose and more frequent administration of opioids in the first days after
      total hip replacement.

PMID- 27048517
TI  - Cognitive Difficulty Intensifies Age-related Changes in Anterior Frontal
      Hemodynamics: Novel Evidence from Near-infrared Spectroscopy.
AB  - Alongside age-related brain deterioration, cognitive functioning declines,
      particularly for more demanding tasks. Past research indicates that, to offset
      this decline, older adults exhibit hemodynamic changes consistent with
      recruitment of more anterior brain regions. However, the nature of the
      hemodynamic changes remains unclear. To address this knowledge gap, we used near
      infrared spectroscopy in 36 young adults (aged 18-30 years) and 36 older adults
      (aged 60-72 years) to assess anterior frontal hemodynamic responses to engagement
      in three cognitive tasks of increasing difficulty. Behavioral results for all
      three tasks confirmed aging deficits (evidenced by slower reaction times and
      reduced accuracy rates) that progressively increased with task difficulty.
      Hemodynamic results showed opposing effects in young versus older adults, with
      oxygenated and total hemoglobin decreasing in young but increasing in older
      adults, particularly during the harder tasks. Also, tissue oxygenation increased
      only in older adults during the harder tasks. Among the older adults only,
      anterior frontal hemodynamic changes correlated with better cognitive
      performance, indicating that they were compensatory in nature. These findings
      provide novel evidence of age-related anterior frontal hemodynamic changes that
      intensify with cognitive demands and compensate for performance deficits.

PMID- 27048518
TI  - Expression and functional analysis of the Wnt/beta-catenin induced mir-135a-2
      locus in embryonic forebrain development.
AB  - BACKGROUND: Brain size and patterning are dependent on dosage-sensitive morphogen
      signaling pathways - yet how these pathways are calibrated remains enigmatic.
      Recent studies point to a new role for microRNAs in tempering the spatio-temporal
      range of morphogen functions during development. Here, we investigated the role
      of miR-135a, derived from the mir-135a-2 locus, in embryonic forebrain
      development. METHOD: 1. We characterized the expression of miR-135a, and its host
      gene Rmst, by in situ hybridization (ish). 2. We conditionally ablated, or
      activated, beta-catenin in the dorsal forebrain to determine if this pathway was
      necessary and/or sufficient for Rmst/miR-135a expression. 3. We performed
      bioinformatics analysis to unveil the most predicted pathways targeted by miR
      135a. 4. We performed gain and loss of function experiments on mir-135a-2 and
      analyzed by ish the expression of key markers of cortical hem, choroid plexus,
      neocortex and hippocampus. RESULTS: 1. miR-135a, embedded in the host long non
      coding transcript Rmst, is robustly expressed, and functional, in the medial wall
      of the embryonic dorsal forebrain, a Wnt and TGFbeta/BMP-rich domain. 2.
      Canonical Wnt/beta-catenin signaling is critical for the expression of Rmst and
      miR-135a, and the cortical hem determinant Lmx1a. 3. Bioinformatics analyses
      reveal that the Wnt and TGFbeta/BMP cascades are among the top predicted pathways
      targeted by miR-135a. 4. Analysis of mir-135a-2 null embryos showed that dorsal
      forebrain development appeared normal. In contrast, modest mir-135a-2
      overexpression, in the early dorsal forebrain, resulted in a phenotype resembling
      that of mutants with Wnt and TGFbeta/BMP deficits - a smaller cortical hem and
      hippocampus primordium associated with a shorter neocortex as well as a less
      convoluted choroid plexus. Interestingly, late overexpression of mir-135a-2
      revealed no change. CONCLUSIONS: All together, our data suggests the existence of
      a Wnt/miR-135a auto-regulatory loop, which could serve to limit the extent, the
      duration and/or intensity of the Wnt and, possibly, the TGFbeta/BMP pathways.

PMID- 27048519
TI  - Eardrum thickening approach for the treatment of patulous Eustachian tube.
AB  - This study aims to explore the eardrum thickening approach via cartilage
      myringoplasty for the cessation of symptoms of patulous Eustachian tube (PET),
      including autophony, aural fullness and breathing synchronous tinnitus. A total
      of 12 patients who met the diagnosis criteria of PET were included and given an
      eardrum patching test preoperatively. Then, myringoplasty with ipsilateral full
      thickness tragus cartilage under general anesthesia was performed. All patients
      were followed up for at least 6 months postoperatively. Gross movements of the
      eardrum under deep respiration disappeared and symptoms were relieved in all
      patients during the patching test and at 1 month after surgery. All patients were
      followed up for a length that varied from 6 months to 5 years postoperatively,
      which demonstrated sustained satisfactory symptom cessation. PET symptoms may
      have been possibly caused by the gross outward movements of the acoustic
      transmission system. The eardrum thickening approach via myringoplasty with full
      thickness tragus cartilage can be an accessible choice for PET with permanent
      satisfactory control of symptoms. Furthermore, the preoperative patching test
      could be a valid way to predict the outcome of the surgery.

PMID- 27048520
TI  - An overview of occupational hazards amongst UK Otolaryngologists.
AB  - Occupational-related hazards (OH) are noted to be prevalent within the medical
      community. However, there is limited evidence of its effects amongst ENT
      surgeons. A national survey was carried out with the assistance of ENT-UK to
      investigate the prevalence of various OH amongst ENT doctors in the UK. A
      literature search was also conducted to search for articles within English
      literature worldwide on this subject. 70.6 % of the responding 323 ENT surgeons
      had reported a form of OH throughout their career. Musculoskeletal pain was the
      most commonly reported (47.4 %) followed by stress/psychiatric morbidities (38.4
      %) and sharps injuries (26.6 %). We found no correlation between OH and
      consultants/non-consultant status, time spent in ENT and subspecialty. Our
      literature search revealed 16 articles pertaining to OH amongst ENT doctors. OHs
      are prevalent within the UK ENT community. There is good evidence within
      literature on musculoskeletal pain, however, higher level studies are required to
      thoroughly investigate the other hazards. 

PMID- 27048521
TI  - Elective neck management for squamous cell carcinoma metastatic to the parotid
      area lymph nodes.
AB  - The objective of this study is to determine if radiotherapy (RT) alone to the
      cervical lymphatics is a suitable alternative to elective neck dissection (END)
      in patients who undergo parotidectomy and postoperative RT for squamous cell
      carcinoma metastatic to the parotid area lymph nodes (PALN). We retrospectively
      reviewed the medical records of 107 patients consecutively treated from November
      1969 to March 2012 for cutaneous squamous cell carcinoma metastatic to the PALN
      with a clinically node-negative neck. Primary therapy consisted of parotidectomy
      in all cases. We compared regional (cervical) control in two subgroups: 42
      patients treated with END and RT and 65 patients treated with elective neck
      irradiation (ENI) alone. The median time of follow-up was 5.5 years (range 0.3-30
      years) for all patients and 11 years for living patients (range 1.8-26 years).
      There was 1 neck recurrence in each subgroup: END and RT, 1/42 (2 %); and ENI
      alone, 1/65 (1.5 %). No patient experienced a complication related to neck RT.
      ENI to a dose of approximately 50-60 Gy is a suitable alternative to END and
      postoperative RT in patients with squamous cell carcinoma metastatic to the PALN.

PMID- 27048523
TI  - Application of a new real-time polymerase chain reaction assay for surveillance
      studies of lymphocystis disease virus in farmed gilthead seabream.
AB  - BACKGROUND: Lymphocystis disease (LCD) is the main viral infection reported to
      affect cultured gilthead seabream (Sparus aurata) in Europe. The existence of
      subclinical Lymphocystis disease virus (LCDV) infection in this fish species has
      been recognised by using polymerase chain reaction (PCR)-based methods.
      Nevertheless, these methods do not provide quantitative results that can be
      useful in epidemiological and pathological studies. Moreover, carrier fish have
      been involved in viral transmission, therefore the use of specific and sensitive
      diagnostic methods to detect LCDV will be relevant for LCD prevention. RESULTS:
      We have developed a real-time PCR (qPCR) assay to detect and quantify LCDV. The
      assay was evaluated for viral diagnosis in surveillance studies in gilthead
      seabream farms, and also to identify viral reservoirs in a hatchery. The
      prevalence of LCDV infection in the asymptomatic gilthead seabream populations
      tested varied from 30 to 100 %, including data from one farm without previous
      records of LCD. Estimated viral load in caudal fin of subclinically infected fish
      was two to five orders of magnitude lower than in diseased fish. The qPCR assay
      allowed the detection of carrier fish in broodstock from a farm with a history of
      clinical LCD in juvenile fish. In addition, the quantitative detection of LCDV
      was achieved in all samples collected in the hatchery, including fertilized eggs,
      larvae and fingerlings, and also rotifer cultures and artemia metanauplii and
      cysts used for larval rearing. CONCLUSIONS: The qPCR assay developed in this
      study has proved to be a rapid, sensitive, and reliable method for LCDV
      diagnosis, which could be valuable to identify LCDV reservoirs or to study viral
      replication in gilthead seabream.

PMID- 27048522
TI  - Addressing Pediatric Obesity in Ambulatory Care: Where Are We and Where Are We
      Going?
AB  - Since the "2007 summary report of child and adolescent overweight and obesity
      treatment" published by Barlow, many obesity intervention studies have been
      conducted in pediatric ambulatory care. Although several meta-analyses have been
      published in the interim, many studies were excluded because of the focus and
      criteria of these meta-analyses. Therefore, the primary goal of this article was
      to identify randomized case-control trials conducted in the primary care setting
      and to report on treatment approaches, challenges, and successes. We have
      developed four themes for our discussion and provide a brief summary of our
      findings. Finally, we identified major gaps and potential solutions and describe
      several urgent key action items. 

PMID- 27048524
TI  - Necessity of office visits for acute respiratory infections in primary care.
AB  - BACKGROUND: Acute respiratory infections (ARIs) are the most common symptomatic
      reason to seek ambulatory care, but many ARI visits may not be necessary.
      OBJECTIVE: To measure the proportion of primary care ARI visits that may not
      require an office visit. METHODS: We identified 58398 ARI visits to 14 primary
      care practices between May 2011 and May 2012 and randomly selected 500 visits,
      439 of which were new ARI visits. We separated non-visit-required information
      [e.g. history of present illness (HPI), past medical history, etc.] from
      information that required an office visit (e.g. physical exam, testing, etc.).
      Reviewing non-visit-required information, we identified the diagnosis (HPI
      diagnosis) and whether office visit appeared necessary. Independently, we
      reviewed the visit-required information and determined if the visit changed
      antibiotic management. RESULTS: Based on non-visit-required information, 72%
      (316/439) of visits did not appear to require an office visit. The most common
      diagnoses were non-specific upper respiratory infection (39%), sinusitis (24%)
      and acute bronchitis (22%). The HPI diagnosis was an exact match for clinicians'
      diagnosis in 67% (213/316) of visits. After reviewing the visit-required
      information, antibiotic management did not change for 87% (276/316) of visits.
      For the remaining 13% (40/316) for which the visit changed management, the
      clinician prescribed an antibiotic for an antibiotic-appropriate diagnosis (65%;
      26/40); prescribed an antibiotic for a non-antibiotic-appropriate diagnosis (25%;
      10/40); or avoided an antibiotic prescription for patients with an HPI diagnosis
      of sinusitis (10%; 4/40). CONCLUSION: About two-thirds of primary care ARI visits
      may not be necessary for appropriate antibiotic management.

PMID- 27048525
TI  - Point-of-care testing in UK primary care: a survey to establish clinical needs.
AB  - BACKGROUND: A number of point-of-care diagnostic tests are commercially available
      in the UK, however, not much is known regarding GPs' desire for these tests or
      the clinical areas of interest. OBJECTIVE: We sought to establish for which
      conditions point-of-care tests (POCTs) would be most helpful to UK GPs for
      diagnosis, reduction of referrals, and monitoring of chronic conditions. METHODS:
      A total of 1635 regionally representative GPs were invited to complete an online
      cross-sectional survey between 31 September and 16 October 2012. RESULTS: A total
      of 1109 (68%) GPs responded to the survey. The most frequently cited conditions
      were urinary tract infections for diagnosis (47% of respondents), pulmonary
      embolism/deep vein thrombosis for referral reduction (47%) and international
      normalized ratio/anticoagulation for monitoring (49%). CONCLUSIONS: This survey
      has identified the conditions for which UK GPs would find POCTs most helpful.
      Comments by respondents suggest that quite radical system-level adjustments will
      be required to allow primary care clinicians to capitalize on the potential
      benefits of POCTs.

PMID- 27048526
TI  - Mesenteric panniculitis: systematic review of cross-sectional imaging findings
      and risk of subsequent malignancy.
AB  - OBJECTIVES: Systematic review to determine any association between imaging
      features of idiopathic mesenteric panniculitis (MP) and subsequent malignancy.
      METHODS: Two researchers searched primary literature independently for imaging
      studies of MP. They extracted data focusing on methodology for unbiased patient
      accrual and capability to determine a link between MP and subsequent malignancy.
      They noted imaging features of MP. Data were accrued and meta-analysis intended.
      RESULTS: Fourteen of 675 articles were eligible; 1,226 patients. Only three (21
      %) accrued patients prospectively. Twelve (86 %) studies described CT features.
      Follow-up varied widely; 1 month to 8 years. Prevalence of MP was influenced by
      accrual: 0.2 % for keyword search versus 1.7 % for consecutive series. Accrual
      bias affected nine (64 %) studies. 458 (38 %) of 1,209 patients had malignancy at
      accrual but varied widely (8-89 %), preventing meta-analysis. Sixty (6.4 %) of
      933 patients developed new malignancy subsequently, also varying widely (0-11 %).
      Of just four studies that determined the proportion of unselected, consecutive
      patients with MP developing subsequent malignancy, three were retrospective and
      the fourth excluded patients with lymphadenopathy, likely excluding patients with
      MP. CONCLUSION: Studies were heterogeneous, with biased accrual. No available
      study can determine an association between MP and subsequent malignancy with
      certainty. KEY POINTS: * Our systematic review of mesenteric panniculitis found
      that imaging studies were biased. * Spectrum and recruitment bias was largely due
      to retrospective study designs. * No study could confirm a certain link between
      mesenteric panniculitis and subsequent malignancy. * Excessive methodological
      heterogeneity precluded meaningful meta-analysis. * High-quality research linking
      mesenteric panniculitis imaging features and subsequent malignancy is needed.

PMID- 27048527
TI  - Software performance in segmenting ground-glass and solid components of subsolid
      nodules in pulmonary adenocarcinomas.
AB  - OBJECTIVE: To evaluate the performance of software in segmenting ground-glass and
      solid components of subsolid nodules in pulmonary adenocarcinomas. METHOD:
      Seventy-three pulmonary adenocarcinomas manifesting as subsolid nodules were
      included. Two radiologists measured the maximal axial diameter of the ground
      glass components on lung windows and that of the solid components on lung and
      mediastinal windows. Nodules were segmented using software by applying five (-850
      HU to -650 HU) and nine (-130 HU to -500 HU) attenuation thresholds. We compared
      the manual and software measurements of ground-glass and solid components with
      pathology measurements of tumour and invasive components. RESULTS: Segmentation
      of ground-glass components at a threshold of -750 HU yielded mean differences of
      +0.06 mm (p = 0.83, 95 % limits of agreement, 4.51 to 4.67) and -2.32 mm (p <
      0.001, -8.27 to 3.63) when compared with pathology and manual measurements,
      respectively. For solid components, mean differences between the software (at 
      350 HU) and pathology measurements and between the manual (lung and mediastinal
      windows) and pathology measurements were -0.12 mm (p = 0.74, -5.73 to 5.55]),
      0.15 mm (p = 0.73, -6.92 to 7.22), and -1.14 mm (p < 0.001, -7.93 to 5.64),
      respectively. CONCLUSION: Software segmentation of ground-glass and solid
      components in subsolid nodules showed no significant difference with pathology.
      KEY POINTS: * Software can effectively segment ground-glass and solid components
      in subsolid nodules. * Software measurements show no significant difference with
      pathology measurements. * Manual measurements are more accurate on lung windows
      than on mediastinal windows.

PMID- 27048528
TI  - MRI texture analysis (MRTA) of T2-weighted images in Crohn's disease may provide
      information on histological and MRI disease activity in patients undergoing ileal
      resection.
AB  - OBJECTIVES: To associate MRI textural analysis (MRTA) with MRI and histological
      Crohn's disease (CD) activity. METHODS: Sixteen patients (mean age 39.5 years, 9
      male) undergoing MR enterography before ileal resection were retrospectively
      analysed. Thirty-six small (<=3 mm) ROIs were placed on T2-weighted images and
      location-matched histological acute inflammatory scores (AIS) measured. MRI
      activity (mural thickness, T2 signal, T1 enhancement) (CDA) was scored in large
      ROIs. MRTA features (mean, standard deviation, mean of positive pixels (MPP),
      entropy, kurtosis, skewness) were extracted using a filtration histogram
      technique. Spatial scale filtration (SSF) ranged from 2 to 5 mm. Regression
      (linear/logistic) tested associations between MRTA and AIS (small ROIs), and
      CDA/constituent parameters (large ROIs). RESULTS: Skewness (SSF = 2 mm) was
      associated with AIS [regression coefficient (rc) 4.27, p = 0.02]. Of 120 large
      ROI analyses (for each MRI, MRTA feature and SSF), 15 were significant. Entropy
      (SSF = 2, 3 mm) and kurtosis (SSF = 3 mm) were associated with CDA (rc 0.9, 1.0, 
      0.45, p = 0.006-0.01). Entropy and mean (SSF = 2-4 mm) were associated with T2
      signal [odds ratio (OR) 2.32-3.16, p = 0.02-0.004], [OR 1.22-1.28, p = 0.03
      0.04]. MPP (SSF = 2 mm) was associated with mural thickness (OR 0.91, p = 0.04).
      Kurtosis (SSF = 3 mm), standard deviation (SSF = 5 mm) were associated with
      decreased T1 enhancement (OR 0.59, 0.42, p = 0.004, 0.007). CONCLUSIONS: MRTA
      features may be associated with CD activity. KEY POINTS: * MR texture analysis
      features may be associated with Crohn's disease histological activity. * Texture
      analysis features may correlate with MR-dependent Crohn's disease activity
      scores. * The utility of MR texture analysis in Crohn's disease merits further
      investigation.

PMID- 27048529
TI  - Incidence and management of oesophageal ruptures following fluoroscopic balloon
      dilatation in children with benign strictures.
AB  - OBJECTIVES: The purpose of this study is to investigate the incidence and
      management of oesophageal ruptures following fluoroscopic balloon dilatation
      (FBD) in children with benign oesophageal strictures. METHODS: Sixty-two children
      with benign oesophageal strictures underwent FBDs. Oesophageal rupture was
      categorized as intramural (type 1), transmural (type 2), or transmural with free
      leakage (type 3). The possible risk factors for oesophageal ruptures were
      analyzed. RESULTS: One hundred and twenty-nine FBDs were performed in these
      patients. The oesophageal rupture rate was 17.1 % (22/129). The majority (21/22)
      of ruptures were type 1 and type 2, both were treated conservatively. Only one
      patient had a type 3 rupture and underwent oesophagoesophagostomy. The patient
      gender, age, and the length and cause of the stricture showed no significant
      effect on the rupture (P > 0.05). However, for the patients <=2 years old, the
      initial balloon with a diameter >=10 mm showed a higher oesophageal rupture rate
      than those <10 mm during the first session (P = 0.03). CONCLUSIONS: Although the
      oesophageal rupture rate in children was 17.1 %, the type 3 rupture rate was 0.8
      %, which usually requires aggressive treatment. For children <=2 years old, the
      initial balloon diameter should be <10 mm in the first session for decreasing the
      risk of oesophageal rupture. KEY POINTS: * The oesophageal rupture rate following
      balloon dilatation in children was 17.1 %. * The incidence of transmural rupture
      with free leakage is very low. * Only transmural rupture with free leakage needs
      aggressive treatment. * For children <=2 years, the initial balloon diameter
      should be <10 mm.

PMID- 27048530
TI  - CT dose survey in adults: what sample size for what precision?
AB  - OBJECTIVES: To determine variability of volume computed tomographic dose index
      (CTDIvol) and dose-length product (DLP) data, and propose a minimum sample size
      to achieve an expected precision. METHODS: CTDIvol and DLP values of 19,875
      consecutive CT acquisitions of abdomen (7268), thorax (3805), lumbar spine
      (3161), cervical spine (1515) and head (4106) were collected in two centers.
      Their variabilities were investigated according to sample size (10 to 1000
      acquisitions) and patient body weight categories (no weight selection, 67-73 kg
      and 60-80 kg). The 95 % confidence interval in percentage of their median
      (CI95/med) value was calculated for increasing sample sizes. We deduced the
      sample size that set a 95 % CI lower than 10 % of the median (CI95/med <= 10 %).
      RESULTS: Sample size ensuring CI95/med <= 10 %, ranged from 15 to 900 depending
      on the body region and the dose descriptor considered. In sample sizes
      recommended by regulatory authorities (i.e., from 10-20 patients), mean CTDIvol
      and DLP of one sample ranged from 0.50 to 2.00 times its actual value extracted
      from 2000 samples. CONCLUSIONS: The sampling error in CTDIvol and DLP means is
      high in dose surveys based on small samples of patients. Sample size should be
      increased at least tenfold to decrease this variability. KEY POINTS: *
      Variability of dose descriptors is high regardless of the body region. *
      Variability of dose descriptors depends on weight selection and the region
      scanned. * Larger samples would reduce sampling errors of radiation dose data in
      surveys. * Totally or partially disabling AEC reduces dose variability and
      increases patient dose. * Median values of dose descriptors depend on the body
      weight selection.

PMID- 27048531
TI  - Different diagnostic values of imaging parameters to predict pseudoprogression in
      glioblastoma subgroups stratified by MGMT promoter methylation.
AB  - OBJECTIVES: The aim of this study was to determine whether diffusion and
      perfusion imaging parameters demonstrate different diagnostic values for
      predicting pseudoprogression between glioblastoma subgroups stratified by O6
      mythylguanine-DNA methyltransferase (MGMT) promoter methylation status. METHODS:
      We enrolled seventy-five glioblastoma patients that had presented with enlarged
      contrast-enhanced lesions on magnetic resonance imaging (MRI) one month after
      completing concurrent chemoradiotherapy and undergoing MGMT promoter methylation
      testing. The imaging parameters included 10 or 90 % histogram cutoffs of apparent
      diffusion coefficient (ADC10), normalized cerebral blood volume (nCBV90), and
      initial area under the time signal-intensity curve (IAUC90). The results of the
      areas under the receiver operating characteristic curve (AUCs) with cross
      validation were compared between MGMT methylation and unmethylation groups.
      RESULTS: MR imaging parameters demonstrated a trend toward higher accuracy in the
      MGMT promoter methylation group than in the unmethylation group (cross-validated
      AUCs = 0.70-0.95 and 0.56-0.87, respectively). The combination of MGMT
      methylation status with imaging parameters improved the AUCs from 0.70 to 0.75
      0.90 for both readers in comparison with MGMT methylation status alone. The
      probability of pseudoprogression was highest (95.7 %) when nCBV90 was below 4.02
      in the MGMT promoter methylation group. CONCLUSIONS: MR imaging parameters could
      be stronger predictors of pseudoprogression in glioblastoma patients with the
      methylated MGMT promoter than in patients with the unmethylated MGMT promoter.
      KEY POINTS: * The glioblastoma subgroup was stratified according to MGMT promoter
      methylation status. * Diagnostic values of diffusion and perfusion parameters for
      predicting pseudoprogression were compared. * Imaging parameters showed higher
      diagnostic accuracy in the MGMT promoter methylation group. * Imaging parameters
      were independent to MGMT promoter methylation status for predicting
      pseudoprogression. * Imaging biomarkers might demonstrate different diagnostic
      values according to MGMT promoter methylation.

PMID- 27048532
TI  - Speeding up PET/MR for cancer staging of children and young adults.
AB  - OBJECTIVE: Combining 18F-FDG PET with whole-body MR for paediatric cancer staging
      is practically feasible if imaging protocols can be streamlined. We compared 18F
      FDG PET/STIR with accelerated 18F-FDG PET/FSPGR for whole-body tumour imaging in
      children and young adults. METHODS: Thirty-three children and young adults (17.5
      +/- 5.5 years, range 10-30) with malignant lymphoma or sarcoma underwent a 18F
      FDG PET staging examination, followed by ferumoxytol-enhanced STIR and FSPGR
      whole-body MR. 18F-FDG PET scans were fused with MR data and the number and
      location of tumours on each integrated examination were determined.
      Histopathology and follow-up imaging served as standard of reference. The
      agreement of each MR sequence with the reference and whole-body imaging times
      were compared using Cohen's kappa coefficient and Student's t-test, respectively.
      RESULTS: Comparing 18F-FDG PET/FSPGR to 18F-FDG PET/STIR, sensitivities were 99.3
      % for both, specificities were statistically equivalent, 99.8 versus 99.9 %, and
      the agreement with the reference based on Cohen's kappa coefficient was also
      statistically equivalent, 0.989 versus 0.992. However, the total scan-time for
      accelerated FSPGR of 19.8 +/- 5.3 minutes was significantly shorter compared to
      29.0 +/- 7.6 minutes for STIR (p = 0.001). CONCLUSION: F-FDG PET/FSPGR
      demonstrated equivalent sensitivities and specificities for cancer staging
      compared to 18F-FDG PET/STIR, but could be acquired with shorter acquisition
      time. KEY POINTS: * Breath-hold FSPGR sequences shorten the data acquisition time
      for whole-body MR and PET/MR. * Ferumoxytol provides long-lasting vascular
      contrast for whole-body MR and PET/MR. * 18 F-FDG PET/FSPGR data provided equal
      sensitivity and specificity for cancer staging compared to 18 F-FDG PET/STIR.

PMID- 27048533
TI  - Detection of Functional Homotopy in Traumatic Axonal Injury.
AB  - OBJECTIVE: This study aimed to explore the interhemispheric intrinsic
      connectivity in traumatic axonal injury (TAI) patients. METHODS: Twenty-one
      patients with TAI (14 males, seven females; mean age, 38.71 +/- 15.25 years) and
      22 well-matched healthy controls (16 males, six females; mean age, 38.50 +/-
      13.82 years) were recruited, and from them we obtained resting-state fMRI data.
      Interhemispheric coordination was examined using voxel-mirrored homotopic
      connectivity (VMHC) and seed-based functional connectivity analysis was
      performed. RESULTS: We observed significantly decreased VMHC in a number of
      regions in TAI patients, including the prefrontal, temporal, occipital, parietal,
      and posterior cingulate cortices, thalami and cerebellar posterior lobes.
      Subsequent seed-based functional connectivity analysis revealed widely disrupted
      functional connectivity between the regions of local homotopic connectivity
      deficits and other areas of the brain, particularly the areas subserving the
      default, salience, integrative, and executive systems. The lower VMHC of the
      inferior frontal gyrus and basal ganglia, thalamus, and caudate were significant
      correlated with the Beck Depression Inventory score, Clinical Dementia Rating
      score, and Mini-Mental State Examination score, respectively. CONCLUSION: TAI is
      associated with regionally decreased interhemispheric interactions and
      extensively disrupted seed-based functional connectivity, generating further
      evidence of diffuse disconnection being associated with clinical symptoms in TAI
      patients. KEY POINTS: * Traumatic axonal injury is associated with decreased
      interhemispheric connectivity * Traumatic axonal injury couples with widely
      disrupted functional connectivity * These alterations support the default,
      salience, integrative, and executive functions.

PMID- 27048534
TI  - Appearances of screen-detected versus symptomatic colorectal cancers at CT
      colonography.
AB  - OBJECTIVES: The aim of this study was to compare the morphology, radiological
      stage, conspicuity, and computer-assisted detection (CAD) characteristics of
      colorectal cancers (CRC) detected by computed tomographic colonography (CTC) in
      screening and symptomatic populations. METHODS: Two radiologists independently
      analyzed CTC images from 133 patients diagnosed with CRC in (a) two randomized
      trials of symptomatic patients (35 patients with 36 tumours) and (b) a screening
      program using fecal occult blood testing (FOBt; 98 patients with 100 tumours),
      measuring tumour length, volume, morphology, radiological stage, and subjective
      conspicuity. A commercial CAD package was applied to both datasets. We compared
      CTC characteristics between screening and symptomatic populations with
      multivariable regression. RESULTS: Screen-detected CRC were significantly smaller
      (mean 3.0 vs 4.3 cm, p < 0.001), of lower volume (median 9.1 vs 23.2 cm3, p <
      0.001) and more frequently polypoid (34/100, 34 % vs. 5/36, 13.9 %, p = 0.02)
      than symptomatic CRC. They were of earlier stage than symptomatic tumours (OR =
      0.17, 95 %CI 0.07-0.41, p < 0.001), and were judged as significantly less
      conspicuous (mean conspicuity 54.1/100 vs. 72.8/100, p < 0.001). CAD detection
      was significantly lower for screen-detected (77.4 %; 95 %CI 67.9-84.7 %) than
      symptomatic CRC (96.9 %; 95 %CI 83.8-99.4 %, p = 0.02). CONCLUSIONS: Screen
      detected CRC are significantly smaller, more frequently polypoid, subjectively
      less conspicuous, and less likely to be identified by CAD than those in
      symptomatic patients. KEY POINTS: * Screen-detected colorectal cancers (CRC) are
      significantly smaller than symptomatic CRC. * Screening cases are significantly
      less conspicuous to radiologists than symptomatic tumours. * Screen-detected CRC
      have different morphology compared to symptomatic tumours (more polypoid, fewer
      annular). * A commercial computer-aided detection (CAD) system was significantly
      less likely to note screen-detected CRC.

PMID- 27048535
TI  - Three-dimensional C-arm CT-guided transjugular intrahepatic portosystemic shunt
      placement: Feasibility, technical success and procedural time.
AB  - OBJECTIVES: Establishment of transjugular intrahepatic portosystemic shunts
      (TIPS) constitutes a standard procedure in patients suffering from portal
      hypertension. The most difficult step in TIPS placement is blind puncture of the
      portal vein. This study aimed to evaluate three-dimensional mapping of portal
      vein branches and targeted puncture of the portal vein. METHODS: Twelve
      consecutive patients suffering from refractory ascites by liver cirrhosis were
      included in this retrospective study to evaluate feasibility, technical success
      and procedural time of C-arm CT-targeted puncture of the portal vein. As a
      control, 22 patients receiving TIPS placement with fluoroscopy-guided blind
      puncture were included to compare procedural time. RESULTS: Technical success
      could be obtained in 100 % of the study group (targeted puncture) and in 95.5 %
      of the control group (blind puncture). Appropriate, three-dimensional C-arm CT
      guided mapping of the portal vein branches could be achieved in all patients. The
      median number of punctures in the C-arm CT-guided study group was 2 +/- 1.3
      punctures. Procedural time was significantly lower in the study group (14.8 +/-
      8.2 min) compared to the control group (32.6 +/- 22.7 min) (p = 0.02).
      CONCLUSIONS: C-arm CT-guided portal vein mapping is technically feasible and a
      promising tool for TIPS placement resulting in a significant reduction of
      procedural time. KEY POINTS: * C-arm CT-mapping of the portal vein for 3D TIPS
      guidance is feasible. * Targeted punctures of the portal vein by C-arm CT reduce
      procedural time. * A decreased number of punctures could improve patient safety.

PMID- 27048537
TI  - Erratum to: Performance of ultralow-dose CT with iterative reconstruction in lung
      cancer screening: limiting radiation exposure to the equivalent of conventional
      chest X-ray imaging.

PMID- 27048536
TI  - Clinical and Ultrasonographic Features of Secondary Intussusception in Children.
AB  - OBJECTIVES: The aim of this study was to review the ultrasonographic features of
      secondary intussusception (SI) in children and assess the value of ultrasound in
      the diagnosis of pediatric SI. METHODS: The authors performed a retrospective
      analysis on the ultrasound findings of 1977 cases of primary intussusception (PI)
      and 37 cases of SI in children. The SI cases were diagnosed by ultrasonography
      and confirmed by laparotomy or histopathologic diagnosis. The clinical and
      ultrasonographic features were analyzed and compared between these two groups.
      RESULTS: The age, no flatus or defecation, position, diameter and length of
      intussusception, the presence of free intraperitoneal liquid, and intestinal
      dialation at the proximal end present, all contributed to the differentiation
      between PI and SI (all P < 0.05). Ultrasound was able to demonstrate the
      pathological lead point (PLP) shadows in all of the 37 SI cases, either in the
      cervical part or intussusceptum of the intussusception. Among the 37 SI patients,
      21 cases (56.8 %) were accurately categorized with lesions, including intestinal
      polyps, cystic intestinal duplication, intestinal wall lymphoma, and a small part
      of Meckel's diverticulum. CONCLUSIONS: Ultrasound can be used as a feasible and
      effective method to discriminate PI from SI. Once the PLP is detected, a definite
      diagnosis can be made. KEY POINTS: * The clinical and ultrasonographic features
      were compared between SI and PI. * The age, location, diameter and length of
      intussusception, and intestinal dilation were distinguishing features. * The
      causes of SI were found to be polyps, intestinal duplication, lymphoma, and
      Meckel's diverticulum. * Ultrasound can be used as an important method to
      diagnose SI. * Demonstration and confirmation of PLP are vital to diagnosing SI.

PMID- 27048538
TI  - Region of interest-based versus whole-lung segmentation-based approach for MR
      lung perfusion quantification in 2-year-old children after congenital
      diaphragmatic hernia repair.
AB  - OBJECTIVE: With a region of interest (ROI)-based approach 2-year-old children
      after congenital diaphragmatic hernia (CDH) show reduced MR lung perfusion values
      on the ipsilateral side compared to the contralateral. This study evaluates
      whether results can be reproduced by segmentation of whole-lung and whether there
      are differences between the ROI-based and whole-lung measurements. METHODS: Using
      dynamic contrast-enhanced (DCE) MRI, pulmonary blood flow (PBF), pulmonary blood
      volume (PBV) and mean transit time (MTT) were quantified in 30 children after CDH
      repair. Quantification results of an ROI-based (six cylindrical ROIs generated of
      five adjacent slices per lung-side) and a whole-lung segmentation approach were
      compared. RESULTS: In both approaches PBF and PBV were significantly reduced on
      the ipsilateral side (p always <0.0001). In ipsilateral lungs, PBF of the ROI
      based and the whole-lung segmentation-based approach was equal (p=0.50). In
      contralateral lungs, the ROI-based approach significantly overestimated PBF in
      comparison to the whole-lung segmentation approach by approximately 9.5 %
      (p=0.0013). CONCLUSIONS: MR lung perfusion in 2-year-old children after CDH is
      significantly reduced ipsilaterally. In the contralateral lung, the ROI-based
      approach significantly overestimates perfusion, which can be explained by
      exclusion of the most ventral parts of the lung. Therefore whole-lung
      segmentation should be preferred. KEY POINTS: * Ipsilaterally, absolute lung
      perfusion after CDH is reduced in whole-lung analysis. * Ipsilaterally, the ROI-
      and whole-lung-based approaches generate identical results. * Contralaterally,
      the ROI-based approach significantly overestimates perfusion results. * Whole
      lung should be analysed in MR lung perfusion imaging. * MR lung perfusion
      measurement is a radiation-free parameter of lung function.

PMID- 27048539
TI  - Expert's comment concerning Grand Rounds case entitled "Cervical subtotal en-bloc
      spondylectomy of C6 mesenchymal chondrosarcoma" (Chang-Hwa Lee and Woo-Kie Min);
      Eur Spine J (2015): DOI 10.1007/s00586-015-4297-z.

PMID- 27048540
TI  - Transdiscal screw versus pedicle screw fixation for high-grade L5-S1 isthmic
      spondylolisthesis in patients younger than 60 years: a case-control study.
AB  - PURPOSE: To compare outcomes between transdiscal and conventional pedicle
      fixation for high-grade L5-S1 spondylolisthesis. METHODS: This was a
      retrospective case-control study with patients prospectively followed. Twenty
      five consecutive patients with mean age of 36.7 years underwent transdiscal
      fixation, and 31 other with mean age of 42.0 years to pedicle fixation were
      clinically and radiographically compared. Clinical assessments were performed
      using Oswestry Disability Index (ODI), Core Outcomes Measures Index (COMI), Short
      Form 12 (SF-12), and pain visual analog scale (VAS). Radiographic spinopelvic
      parameters were also evaluated. The mean follow-up was 2.7 years (range 2.0-5.3).
      RESULTS: Preoperative data were comparable between groups. Surgery time, blood
      loss, and hospital stay were similar between groups. At last follow-up, clinical
      and radiographic outcomes were significantly improved in both groups.
      Postoperatively, both lumbar and leg pain VAS were similar between groups, but
      ODI (20.2 vs. 31.6, p = 0.010), COMI (1.6 vs. 2.8, p = 0.012), and SF-12 physical
      (84.3 vs. 61.5, p = 0.004) and mental (81.5 vs. 69.4, p = 0.021) scores were
      significantly better in the transdiscal group. The neurologic complication rate
      was similar in both groups. There were 4 pseudoarthroses in the pedicle group,
      and none in the transdiscal group. CONCLUSION: L5-S1 transdiscal screw fixation
      provided better functional and radiographic outcomes at medium-term than
      conventional pedicle fixation for high-grade spondylolisthesis, although
      transdiscal sacral screws are difficult to place in correct position.

PMID- 27048541
TI  - Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1
      regulates morphology and function of P19C6 cell-derived neurons.
AB  - Glycerophospholipids, which are components of biomembranes, are formed de novo by
      the Kennedy pathway and subsequently mature through the Lands cycle.
      Lysophospholipid acyltransferases (LPLATs) are key enzymes in both pathways and
      influence the fatty acid composition of biomembranes. Neuronal differentiation is
      characterized by neurite outgrowth, which requires biomembrane biosynthesis.
      However, the role of LPLATs in neuronal differentiation remains unknown. In this
      study, we examined whether LPLATs are involved in neuronal differentiation using
      all-trans-retinoic acid (ATRA)-treated P19C6 cells. In these cells, mRNA levels
      of lysophosphatidylethanolamine acyltransferase (LPEAT)-1/membrane-bound O
      acyltransferase (MBOAT)-1 were higher than those in undifferentiated cells. LPEAT
      enzymatic activity increased with 16:0- and 18:1-CoA as acyl donors. When
      LPEAT1/MBOAT1 was knocked down with small interfering RNA (siRNA), outgrowth of
      neurites and expression of neuronal markers decreased in ATRA-treated P19C6
      cells. Voltage-dependent calcium channel activity was also suppressed in these
      cells transfected with LPEAT1/MBOAT1 siRNA. These results suggest that
      LPEAT1/MBOAT1 plays an important role in neurite outgrowth and function.-Tabe,
      S., Hikiji, H., Ariyoshi, W., Hashidate-Yoshida, T., Shindou, H., Okinaga, T.,
      Shimizu, T., Tominaga, K., Nishihara, T. Lysophosphatidylethanolamine
      acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and
      function of P19C6 cell-derived neurons.

PMID- 27048542
TI  - Microporous aluminophosphates synthesized with 1,2,3-trimethylimidazolium and
      fluoride.
AB  - The synthesis of microporous aluminophosphates using 1,2,3-trimethylimidazolium
      (123TMI) and fluoride produces three phases (HPM-3, PST-27 and triclinic AlPO4
      34) depending on the amount of water and organic structure-directing agents in
      the synthesis mixture. Fluoride occluded in double 4-ring units was not detected
      by (19)F MAS NMR spectroscopy in any product. While the structure of HPM-3
      remains unknown, PST-27 has been determined to be a monoclinic version of AlPO4-5
      with a distorted and likely complex structure. Rietveld analysis using
      synchrotron diffraction data for as-made triclinic AlPO4-34 reveals that each of
      its cha-cages holds two 123TMI cations, forming a displaced anti-parallel dimer
      with a short distance between aromatic rings (3.78 A from center to center, 3.63
      A from plane to plane). This suggests that pi-pi interactions may play a role in
      the synthesis of this phase and related CHA-type systems. A study of the optical
      properties of PST-27, AlPO4-34 and other materials containing 123TMI cations
      shows their complex fluorescence behavior, sometimes displaying a red-edge
      effect, i.e., a red shift of the fluorescence as the excitation wavelength is
      shifted toward the red edge of the absorption band. An absorption band at 291 nm
      appears only in the dimer-containing triclinic AlPO4-34 and is sensitive to the
      introduction of Si into the framework.

PMID- 27048543
TI  - On scientific authorship: Proliferation, problems and prospects.

PMID- 27048544
TI  - Care to talk? A framework for appreciative conversations about dementia:
      Innovative practice.
AB  - When people with dementia are admitted to hospital, both they and their carers
      and families have crucial roles to play. They should be positioned as the only
      true experts in the unique individuality of the person and brought into the
      nursing process as an equal partner in care. 'Care to Talk' is a conversational
      model developed through Appreciative Inquiry to facilitate this way of working.
      The model, its development and outcomes are discussed.

PMID- 27048545
TI  - Pilot test of a six-week group delivery caregiver training program to reduce
      sleep disturbances among older adults with dementia (Innovative practice).
AB  - The purpose of the pilot program was to examine the adaptability and feasibility
      of a modified group-delivery sleep education program (NITE-AD) designed to reduce
      nocturnal disturbances in community-dwelling older adults with dementia. We
      recruited seven caregivers of persons with dementia from two adult day care
      centers in South Florida into a six-week group program at adult day care centers.
      A trained sleep educator taught caregivers about the impact of aging and dementia
      on sleep and how non-pharmacological interventions such as increasing light,
      regular exercise, and sleep hygiene strategies can improve sleep in persons with
      dementia. The curriculum incorporated ongoing problem solving and goal setting.
      Results suggest improvement in caregiver depression and persons with dementia
      sleep problems. Caregivers reported that the program provided them support and
      valuable strategies that they will continue to apply. Educating caregivers in a
      group setting about non-pharmacologic strategies for managing sleep may reduce
      caregiver burden and improve sleep among persons with dementia.

PMID- 27048546
TI  - Comparative pharmacological characterization of D1-like dopamine receptors from
      Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus suggests pleiotropic
      signaling in mosquito vector lineages.
AB  - BACKGROUND: Small molecule antagonists of mosquito dopamine receptors (DARs) are
      under investigation as a new class of vector-selective insecticides. Antagonists
      that inhibit the D1-like DARs AaDOP2 and CqDOP2 from the mosquitoes Aedes aegypti
      L. and Culex quinquefasciatus Say, respectively, also cause larval mortality in
      bioassays. Here, we report on the orthologous DAR, AgDOP2, from the malaria
      mosquito Anopheles gambiae Giles that was cloned and pharmacologically
      characterized in HEK293 cells. Larval bioassays were then conducted to examine
      the potential of DAR antagonist insecticides against Anopheles vectors. FINDINGS:
      Previous in vitro cAMP accumulation assays demonstrated Galphas coupling for
      AaDOP2 and CqDOP2 and dose-dependent inhibition by DAR antagonists. We observed a
      negligible response of AgDOP2 in the cAMP assay, which prompted an investigation
      of alternative coupling for mosquito DARs. In an in vitro IP-One Galphaq second
      messenger assay of calcium signaling, dopamine stimulation increased IP1
      accumulation in AaDOP2-, CqDOP2- and AgDOP2-expressing cells, and DAR antagonists
      inhibited IP1 signaling in a dose-dependent manner. In larval bioassays, DAR
      antagonists caused considerable mortality of An. gambiae larvae within 24 h post
      exposure. CONCLUSIONS: In vitro data reveal pleiotropic coupling of AaDOP2 and
      CqDOP2 to Galphaq and Galphas. In contrast, AgDOP2 appeared to selectively couple
      to Galphaq signaling. In vitro antagonist studies revealed general conservation
      in pharmacology between mosquito DARs. In vivo data suggest potential for DAR
      antagonist insecticides against An. gambiae. Sequence conservation among the DOP2
      receptors from 15 Anopheles species indicates utility of antagonists to control
      residual malaria transmission. AgDOP2 Galphaq-dependent signaling could be
      exploited for An. gambiae control via pathway specific antagonists.

PMID- 27048547
TI  - Mood by microbe: towards clinical translation.
AB  - There is a growing realization that the gut-brain axis plays a key role in
      maintaining brain health and the stress response. Recently, the gut microbiota
      has emerged as a master regulator of this axis. Thus, opportunities to exploit
      the microbiome to treat stress-related psychiatric disorders are materializing.
      Clinical validation of such strategies is now warranted. 

PMID- 27048548
TI  - Prevention of inaccurate targeting of proximal screws during reconstruction
      femoral nailing.
AB  - PURPOSE: The purpose of this study was to identify the underlying cause by
      simulating the forces involved in a controlled laboratory setting, and then to
      illustrate some intraoperative tips on how to detect this malalignment and
      suggest solutions prevent this intraoperative complication. METHODS: The Expert
      Asian Femoral Nail (A2FN) and Proximal Femoral Nail Antirotation (PFNA)
      reconstruction nail systems were evaluated to compare the characteristics of each
      nailing system and their reactions to soft tissue tension at the time of proximal
      reconstruction screw placement. Soft tissue tension was simulated by placing a
      fulcrum under the distal drill sleeve and exerting a load on the targeting device
      via the addition of weights. The occurrence and degree of guide malalignment were
      determined while gradually increasing the weight. RESULTS: When soft tissue
      tension was simulated on the drill/guide sleeve of the A2FN, the drill sleeve
      deviated from the proximal screw hole proportionally to the weight applied and
      the K-wire guide passed outside of the nail at a weight of 7 kg. However, the
      drill sleeve of the PFNA was aligned exactly to the center of nail axis and the K
      wire passed cleanly through the proximal locking hole regardless of weight
      applied. CONCLUSIONS: Inaccurate guidance of the screw-targeting device can be
      caused by soft tissue tension. Thus, the authors recommend that careful attention
      be placed on minimizing soft tissue tension during proximal screw placement while
      using the targeting device of the A2FN system.

PMID- 27048549
TI  - [Intraocular lens explantation and secondary implantation of a light-adjustable
      lens. Video article].
AB  - INDICATIONS: The operation is carried out to exchange previously implanted
      intraocular lenses (IOL) because of deviation from the target refraction with
      aniseikonia and anisometropia, in cases of contact lens intolerance,
      dissatisfaction with the IOL due to side effects and particularly problems with
      multifocal lenses. OBJECTIVE AND PRINCIPLES: The aim of this surgical approach is
      to retain the original implantation site of the exchange lens and capsular bag
      integrity with maximum sparing of the zonular fibers and secondary IOL
      implantation with stable positioning for fine adjustment of residual refractive
      errors. OPERATIVE TECHNIQUE: Using a non-astigmatic approach the primary IOL is
      first mobilized and removed. A light-adjustable IOL is then implanted in the
      capsular bag and residual refractive errors in the visual axis are adjusted using
      profiled UV light. The surgical technique is demonstrated in detail with the help
      of a video of the operation, which is available online. RESULTS: Residual
      postoperative deviations from the target refraction of sphere and cylinder up to
      2 diopters can be precisely adjusted noninvasively. Individual alterations of
      asphericity can provide stable distance visual acuity while enhancing near and
      intermediate visual acuity.

PMID- 27048550
TI  - [Comparison of two visual acuity tests in school enrolment examinations :
      Tumbling E test versus Freiburg visual acuity test].
AB  - BACKGROUND: On the initiative of professionals performing vision screening for
      primary school enrolment, we compared the laptop-based Freiburg acuity and
      contrast test (FrACT) as a more easily portable alternative to the traditionally
      employed tumbling E vision test. METHODS: We assessed vision with both methods in
      326 children (647 eyes) aged 3.8-6.9 years. The FrACT was set to present the
      Landolt C optotype with the four cardinal orientations and automatic threshold
      bracketing over 18 presentations. RESULTS: The 95% limits of agreement between
      both methods were +/-0.125 logMAR and 95% of all test differences were within
      slightly more than +/-1 line. Over the examined age range acuity significantly
      but weakly increased (p < 0.01) from 0.7 to 0.9 and for Landolt Cs the acuity
      gain was slightly higher by 0.02 logMAR per year. The FrACT results were >=3
      lines lower than those of the tumbling E chart in only 6 eyes. The examiners
      unanimously preferred FrACT. DISCUSSION: The agreement between both tests of
      approximately +/-1 lines is very high. The low outlier rate of <1% is deemed to
      be acceptable for a screening test.

PMID- 27048551
TI  - School health services and its practice among public and private primary schools
      in Western Nigeria.
AB  - BACKGROUND: Globally the number of children reaching school age is estimated to
      be 1.2 billion children (18% of the world's population) and rising. This study
      was therefore designed to determine the school health services available and its
      practices in primary schools in Ogun state, Western Nigeria. METHODS: The study
      was a comparative cross-sectional survey of private and public primary schools in
      Ogun state using a multi-stage sampling technique. Participants were interviewed
      using a structured, interviewer administered questionnaire and a checklist. Data
      collected was analyzed using the SPSS version 15.0. RESULTS: A total of 360 head
      teachers served as respondents for the study with the overall mean age of 45.7 +/
      9.9 years. More than three quarters of the respondents in both groups could not
      correctly define the school health programme. There were no health personnel or a
      trained first aider in 86 (47.8%) public and 110 (61.1%) private schools but a
      nurse/midwife was present in 57 (31.7%) and 27 (15.0%) public and private
      schools. (chi(2) = 17.122, P = 0.002). In about 95% of the schools, the teacher
      carried out routine inspection of the pupils while periodic medical examination
      for staff and pupils was carried out in only 13 (7.2%) public and 31 (17.2%)
      private schools (chi(2) = 8.398, P = 0.004). A sick bay/clinic was present in 26
      (14.4%) and 67 (37.2%) public and private schools respectively (chi(2) = 24.371,
      P = 0.001). The practice of school health programme was dependent on the age
      (chi(2) = 12.53, P = 0.006) and the ethnicity of the respondents (chi(2) = 6.330,
      P = 0.042). Using multivariate analysis only one variable (type of school) was
      found to be a predictor of school health programme. (OR 4.55, CI 1.918-10.79).
      CONCLUSION: The study concludes that the practice of the various components of
      school health services was poor but better in private primary schools in Nigeria.
      Routine inspection by teachers was the commonest form of health appraisal. This
      may suggest that more health personnel need to be employed to cater for the
      health of the school children in Nigeria and other similar developing countries.

PMID- 27048552
TI  - Colonic stenting as a bridge to surgery for obstructive colorectal cancer:
      advantages and disadvantages.
AB  - PURPOSE: To clarify the advantages and disadvantages of stenting as a bridge to
      surgery (BTS) by comparing the clinical features and outcomes of patients who
      underwent BTS with those of patients who underwent emergency surgery (ES).
      METHODS: We assessed technical success, clinical success, surgical procedures,
      stoma formation, complications, clinicopathological features, and Onodera's
      prognostic nutritional index (OPNI) in patients who underwent BTS and those who
      underwent ES. RESULTS: Twenty-six patients underwent stenting, which was
      successful in 22 (BTS group). The remaining four patients with unsuccessful
      stenting underwent emergency surgery. A total of 22 patients underwent emergency
      surgery (ES group). The rates of technical and clinical success were 85.0 and
      81.0 %, respectively. The proportion of patients able to be treated by
      laparoscopic surgery (P = 0.0001) and avoid colostomy (P = 0.0042) was
      significantly higher in the BTS group. Although the incidence of anastomotic
      leakage in the two groups was not significantly different, it was significantly
      reduced by colonoscopic evaluation of obstructive colitis (P = 0.0251). The mean
      number of harvested lymph nodes (P = 0.0056) and the proportion of D3
      lymphadenectomy (P = 0.0241) were significantly greater in the BTS group.
      Perineural invasion (PNI) was noted in 59.1 and 18.2 % of the BTS group and ES
      group patients, respectively (P = 0.0053). OPNI and serum albumin decreased
      significantly after stenting (P = 0.0084). CONCLUSIONS: The advantages of
      stenting as a BTS were that it avoided colostomy and allowed for laparoscopic
      surgery and lymphadenectomy, whereas its disadvantage lay in the decreased PNI
      and OPNI levels. A larger study including an analysis of prognosis is warranted.

PMID- 27048553
TI  - Diagnosis and treatment of tricuspid valve disease: current and future
      perspectives.
AB  - The assessment and management of tricuspid valve disease have evolved
      substantially during the past several years. Whereas tricuspid stenosis is
      uncommon, tricuspid regurgitation is frequently encountered and is most often
      secondary in nature and caused by annular dilatation and leaflet tethering from
      adverse right ventricular remodelling in response to any of several disease
      processes. Non-invasive assessment of tricuspid regurgitation must define its
      cause and severity; advanced three-dimensional echocardiography, MRI, and CT are
      gaining in clinical application. The indications for tricuspid valve surgery to
      treat tricuspid regurgitation are related to the cause of the disorder, the
      context in which it is encountered, its severity, and its effects on right
      ventricular function. Most operations for tricuspid regurgitation are done at the
      time of left-sided heart valve surgery. The threshold for restrictive ring
      annuloplasty repair of secondary tricuspid regurgitation at the time of left
      sided valve surgery has decreased over time with recognition of the risk of
      progressive tricuspid regurgitation and right heart failure in patients with
      moderate or lesser degrees of tricuspid regurgitation and tricuspid annular
      dilatation, as well as with appreciation of the high risks of reoperative surgery
      for severe tricuspid regurgitation late after left-sided valve surgery. However,
      many patients with unoperated severe tricuspid regurgitation are also deemed at
      very high or prohibitive surgical risk. Novel transcatheter therapies have begun
      to emerge for the treatment of tricuspid regurgitation in such patients.
      Experience with such therapies is preliminary and further studies are needed to
      determine their role in the management of this disorder.

PMID- 27048554
TI  - Improved ROS defense in the swimbladder of a facultative air-breathing erythrinid
      fish, jeju, compared to a non-air-breathing close relative, traira.
AB  - The jeju Hoplerythrinus unitaeniatus and the traira Hoplias malabaricus are two
      closely related erythrinid fish, both possessing a two-chambered physostomous
      swimbladder. In the jeju the anterior section of the posterior bladder is highly
      vascularized and the swimbladder is used for aerial respiration; the traira, in
      turn, is a water-breather that uses the swimbladder as a buoyancy organ and not
      for aerial oxygen uptake. Observation of the breathing behavior under different
      levels of water oxygenation revealed that the traira started aquatic surface
      respiration only under severe hypoxic conditions and did not breathe air. In the
      jeju air-breathing behavior was observed under normoxic conditions, and the
      frequency of air-breathing was significantly increased under hypoxic conditions.
      Unexpectedly, even under hyperoxic conditions (30 mg O2 L(-1)) the jeju continued
      to take air breaths, and compared with normoxic conditions the frequency was not
      reduced. Because the frequently air-exposed swimbladder tissue faces higher
      oxygen partial pressures than normally experienced by other fish tissues, it was
      hypothesized that in the facultative air-breathing jeju, swimbladder tissue would
      have a higher antioxidative capacity than the swimbladder tissue of the water
      breathing traira. Measurement of total glutathione (GSSG/GSH) concentration in
      anterior and posterior swimbladder tissue revealed a higher concentration of this
      antioxidant in swimbladder tissue as compared to muscle tissue in the jeju.
      Furthermore, the GSSG/GSH concentration in jeju tissues was significantly higher
      than in traira tissues. Similarly, activities of enzymes involved in the
      breakdown of reactive oxygen species were significantly higher in the jeju
      swimbladder as compared to the traira swimbladder. The results show that the
      jeju, using the swimbladder as an additional breathing organ, has an enhanced
      antioxidative capacity in the swimbladder as compared to the traira, using the
      swimbladder only as a buoyancy organ.

PMID- 27048555
TI  - Pulmonary haemodynamics are correlated with intimal lesions in a rat model of
      severe PAH: attenuation of pulmonary vascular remodelling with ambrisentan.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by obstructive
      lesions and vasoconstriction of the pulmonary arteries. Early therapeutic
      interventions with vasodilator drugs are thought to be beneficial in PAH.
      However, it remains unknown whether the severity of intimal obstruction is
      associated with increased pulmonary arterial pressure and whether reduction of
      vasoconstriction in the earlier stage by these drugs has a beneficial effect.
      Therefore, the aims of this study were to investigate these issues in a rat model
      of severe PAH. Methods A rat model of severe PAH was created by injection of a
      vascular endothelial growth factor receptor blocker in combination with hypoxia
      for the first 3 weeks followed by normoxia for the next 9 weeks. To assess
      intimal obstruction, "the pulmonary artery occlusion index (PAOI)" was developed
      to digitize all lesions. The small pulmonary arteries were assessed by this
      index, and the association between right ventricular systolic pressure (RVSP) and
      PAOI was investigated. An endothelin receptor antagonist, ambrisentan, was
      administered by gavage to rats during either hypoxia (Prevention study group,
      n=25) or normoxia (Early treatment group, n=15). RESULTS: PAOI showed a positive
      correlation with RVSP, and both RVSP and PAOI increased gradually over time.
      There were no severe occlusive lesions in either group, but the density of
      partially occlusive lesions was significantly decreased in the Prevention study
      group. CONCLUSION: A novel PAOI index was developed, and this index was strongly
      correlated with RVSP. Furthermore, ambrisentan reduced luminal occlusive lesions
      more effectively when treatment was given during the first 2 weeks of hypoxia.

PMID- 27048556
TI  - Nicotinic acid supplementation in diet favored intramuscular fat deposition and
      lipid metabolism in finishing steers.
AB  - Nicotinic acid (NA) acting as the precursor of NAD(+)/NADH and NADP(+)/NADPH,
      participates in many biochemical processes, e.g. lipid metabolism. The main
      purpose of this study was to investigate the effects of dietary NA on carcass
      traits, meat quality, blood metabolites, and fat deposition in Chinese crossbred
      finishing steers. Sixteen steers with the similar body weight and at the age of
      24 months were randomly allocated into control group (feeding basal diet) and NA
      group (feeding basal diet + 1000 mg/kg NA). All experimental cattle were fed a
      90% concentrate diet and 10% forage straw in a 120-day feeding experiment. The
      results showed that supplemental NA in diet increased longissimus area,
      intramuscular fat content (17.14% vs. 9.03%), marbling score (8.08 vs. 4.30),
      redness (a*), and chroma (C*) values of LD muscle, but reduced carcass fat
      content (not including imtramuscular fat), pH24 h and moisture content of LD
      muscle, along with no effect on backfat thickness. Besides, NA supplementation
      increased serum HDL-C concentration, but decreased the serum levels of LDL-C,
      triglyceride, non-esterified fatty acid, total cholesterol, and glycated serum
      protein. In addition, NA supplementation increased G6PDH and ICDH activities of
      LD muscle. These results suggested that NA supplementation in diet improves the
      carcass characteristics and beef quality, and regulates the compositions of serum
      metabolites. Based on the above results, NA should be used as the feed additive
      in cattle industry.

PMID- 27048558
TI  - Impact of thermodilution-derived coronary blood flow patterns after percutaneous
      coronary intervention on mid-term left ventricular remodeling in patients with ST
      elevation myocardial infarction.
AB  - We recently reported the coronary thermodilution curve can be evaluated by
      analyzing the thermodilution curve obtained from a pressure sensor/thermistor
      tipped guidewire, and presence of a bimodal-shaped thermodilution curve following
      primary percutaneous coronary intervention (pPCI) in ST-segment elevation
      myocardial infarction (STEMI) patients was associated with worse outcomes. This
      study evaluated whether the bimodal-shaped thermodilution curve predicts left
      ventricular (LV) remodeling after STEMI. The coronary thermodilution curve
      patterns were evaluated for 75 patients treated by pPCI for their first STEMI
      using a pressure sensor/thermistor-tipped guidewire, and classified into the
      three groups according to the thermodilution curve shape: narrow unimodal (n =
      39), wide unimodal (n = 26), and bimodal pattern (n = 10). Echocardiography was
      performed at baseline and 6 months after STEMI. LV remodeling was defined as a
      >20 % increase in LV end-diastolic volumes (LVEDV). LVEDV at 6-month follow-up
      was greater in the bimodal group than in the other groups (p < 0.001). The
      prevalence of LV remodeling was highest in the bimodal group than in the narrow
      and wide unimodal groups (60, 12, and 15 %, respectively; p = 0.003).
      Multivariate analysis revealed a bimodal-shaped thermodilution curve as an
      independent predictor of the prevalence of LV remodeling. A bimodal-shaped
      thermodilution curve is associated with LV remodeling after STEMI. This easily
      assessable coronary thermodilution curve pattern is useful to predict mid-term LV
      remodeling for STEMI patients at the catheterization laboratory.

PMID- 27048557
TI  - Micro- and nanoparticulates for DNA vaccine delivery.
AB  - DNA vaccination has emerged as a promising alternative to traditional protein
      based vaccines for the induction of protective immune responses. DNA vaccines
      offer several advantages over traditional vaccines, including increased
      stability, rapid and inexpensive production, and flexibility to produce vaccines
      for a wide variety of infectious diseases. However, the immunogenicity of DNA
      vaccines delivered as naked plasmid DNA is often weak due to degradation of the
      DNA by nucleases and inefficient delivery to immune cells. Therefore, biomaterial
      based delivery systems based on micro- and nanoparticles that encapsulate plasmid
      DNA represent the most promising strategy for DNA vaccine delivery.
      Microparticulate delivery systems allow for passive targeting to antigen
      presenting cells through size exclusion and can allow for sustained presentation
      of DNA to cells through degradation and release of encapsulated vaccines. In
      contrast, nanoparticle encapsulation leads to increased internalization, overall
      greater transfection efficiency, and the ability to increase uptake across
      mucosal surfaces. Moreover, selection of the appropriate biomaterial can lead to
      increased immune stimulation and activation through triggering innate immune
      response receptors and target DNA to professional antigen presenting cells.
      Finally, the selection of materials with the appropriate properties to achieve
      efficient delivery through administration routes conducive to high patient
      compliance and capable of generating systemic and local (i.e. mucosal) immunity
      can lead to more effective humoral and cellular protective immune responses. In
      this review, we discuss the development of novel biomaterial-based delivery
      systems to enhance the delivery of DNA vaccines through various routes of
      administration and their implications for generating immune responses.

PMID- 27048559
TI  - Real-time color change monitoring of apple slices using image processing during
      intermittent microwave convective drying.
AB  - An intermittent microwave convective drying method combined with a real-time
      computer vision technique was employed to detect the effect of drying parameters
      on color properties of apple slices. The experiments were performed at air
      temperature of 40 to 80C, air velocities of 1-2 m/s, microwave powers of 200-600
      W, and pulse ratios (PRs) of 2-6. Drying rate and drying time varied from 0.014
      to 0.000001 min-1 and 27 to 244 min, respectively. The normalized lightness
      values had ascending and descending parabolic trends with decrease in product
      moisture content. With descending dimensionless moisture content, redness,
      yellowness, color change, hue angle, and chroma were enlarged. The normalized
      redness values changed from -4 to 3. Models relating drying parameters with
      drying time, drying rate, and lightness were obtained and found to be significant
      (P < 0.01). Results indicated that microwave power and PRs had more influence on
      lightness and color change than other parameters.

PMID- 27048560
TI  - Harm reduction interventions should encompass people who inject image and
      performance enhancing drugs.

PMID- 27048562
TI  - Conclusions of study on height, body mass index, and socioeconomic status have an
      uncertain basis.

PMID- 27048563
TI  - Beyond canonical: The Wnt and beta-catenin story.
AB  - This Editorial Guide uses Wnt-stimulated activation of the transcriptional
      activity of beta-catenin, the canonical Wnt/beta-catenin pathway, to illustrate
      the hazards of limiting research investigation and questions to those that fit
      the "canonical" view. 

PMID- 27048561
TI  - Role of ND10 nuclear bodies in the chromatin repression of HSV-1.
AB  - Herpes simplex virus (HSV) is a neurotropic virus that establishes lifelong
      latent infection in human ganglion sensory neurons. This unique life cycle
      necessitates an intimate relation between the host defenses and virus
      counteractions over the long course of infection. Two important aspects of host
      anti-viral defense, nuclear substructure restriction and epigenetic chromatin
      regulation, have been intensively studied in the recent years. Upon viral DNA
      entering the nucleus, components of discrete nuclear bodies termed nuclear domain
      10 (ND10), converge at viral DNA and place restrictions on viral gene expression.
      Meanwhile the infected cell mobilizes its histones and histone-associated
      repressors to force the viral DNA into nucleosome-like structures and also
      represses viral transcription. Both anti-viral strategies are negated by various
      HSV countermeasures. One HSV gene transactivator, infected cell protein 0 (ICP0),
      is a key player in antagonizing both the ND10 restriction and chromatin
      repression. On one hand, ICP0 uses its E3 ubiquitin ligase activity to target
      major ND10 components for proteasome-dependent degradation and thereafter
      disrupts the ND10 nuclear bodies. On the other hand, ICP0 participates in de
      repressing the HSV chromatin by changing histone composition or modification and
      therefore activates viral transcription. Involvement of a single viral protein in
      two seemingly different pathways suggests that there is coordination in host anti
      viral defense mechanisms and also cooperation in viral counteraction strategies.
      In this review, we summarize recent advances in understanding the role of
      chromatin regulation and ND10 dynamics in both lytic and latent HSV infection. We
      focus on the new observations showing that ND10 nuclear bodies play a critical
      role in cellular chromatin regulation. We intend to find the connections between
      the two major anti-viral defense pathways, chromatin remodeling and ND10
      structure, in order to achieve a better understanding of how host orchestrates a
      concerted defense and how HSV adapts with and overcomes the host immunity. 

PMID- 27048564
TI  - IP3 receptors: Take four IP3 to open.
AB  - Inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors are the
      channels responsible for Ca(2+)release from the endoplasmic and sarcoplasmic
      reticulum. Research inScience Signalingby Alzayadyet al show that all four IP3
      binding sites within the tetrameric IP3R must bind IP3before the channel can
      open, which has important consequences for the distribution of both IP3and IP3R
      activity within cells. 

PMID- 27048565
TI  - Inhibition of class I histone deacetylases blunts cardiac hypertrophy through
      TSC2-dependent mTOR repression.
AB  - Altering chromatin structure through histone posttranslational modifications has
      emerged as a key driver of transcriptional responses in cells. Modulation of
      these transcriptional responses by pharmacological inhibition of class I histone
      deacetylases (HDACs), a group of chromatin remodeling enzymes, has been
      successful in blocking the growth of some cancer cell types. These inhibitors
      also attenuate the pathogenesis of pathological cardiac remodeling by blunting
      and even reversing pathological hypertrophy. The mechanistic target of rapamycin
      (mTOR) is a critical sensor and regulator of cell growth that, as part of mTOR
      complex 1 (mTORC1), drives changes in protein synthesis and metabolism in both
      pathological and physiological hypertrophy. We demonstrated through
      pharmacological and genetic methods that inhibition of class I HDACs suppressed
      pathological cardiac hypertrophy through inhibition of mTOR activity. Mice
      genetically silenced for HDAC1 and HDAC2 had a reduced hypertrophic response to
      thoracic aortic constriction (TAC) and showed reduced mTOR activity. We
      determined that the abundance of tuberous sclerosis complex 2 (TSC2), an mTOR
      inhibitor, was increased through a transcriptional mechanism in cardiomyocytes
      when class I HDACs were inhibited. In neonatal rat cardiomyocytes, loss of TSC2
      abolished HDAC-dependent inhibition of mTOR activity, and increased expression of
      TSC2 was sufficient to reduce hypertrophy in response to phenylephrine. These
      findings point to mTOR and TSC2-dependent control of mTOR as critical components
      of the mechanism by which HDAC inhibitors blunt pathological cardiac growth.
      These results also suggest a strategy to modulate mTOR activity and facilitate
      the translational exploitation of HDAC inhibitors in heart disease. 

PMID- 27048566
TI  - Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to
      initiate Ca2+ release.
AB  - Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are tetrameric intracellular
      Ca(2+)-release channels with each subunit containing a binding site for IP3in the
      amino terminus. We provide evidence that four IP3molecules are required to
      activate the channel under diverse conditions. Comparing the concentration
      response relationship for binding and Ca(2+)release suggested that IP3Rs are
      maximally occupied by IP3before substantial Ca(2+)release occurs. We showed that
      ligand binding-deficient subunits acted in a dominant-negative manner when
      coexpressed with wild-type monomers in the chicken immune cell line DT40-3KO,
      which lacks all three genes encoding IP3R subunits, and confirmed the same effect
      in an IP3R-null human cell line (HEK-3KO) generated by CRISPR/Cas9 technology.
      Using dimeric and tetrameric concatenated IP3Rs with increasing numbers of
      binding-deficient subunits, we addressed the obligate ligand stoichiometry. The
      concatenated IP3Rs with four ligand-binding sites exhibited Ca(2+)release and
      electrophysiological properties of native IP3Rs. However, IP3failed to activate
      IP3Rs assembled from concatenated dimers consisting of one binding-competent and
      one binding-deficient mutant subunit. Similarly, IP3Rs containing two monomers of
      IP3R2short, an IP3binding-deficient splice variant, were nonfunctional.
      Concatenated tetramers containing only three binding-competent ligand-binding
      sites were nonfunctional under a wide range of activating conditions. These data
      provide definitive evidence that IP3-induced Ca(2+)release only occurs when each
      IP3R monomer within the tetramer is occupied by IP3, thereby ensuring fidelity of
      Ca(2+)release. 

PMID- 27048568
TI  - Depressive Symptoms Among Older Chinese Americans: Examining the Role of
      Acculturation and Family Dynamics.
AB  - Objectives: This study identified the prevalence of depression and tested the
      influence of acculturation and family dynamics on depressive symptoms, among a
      community sample of older Chinese Americans. Method: Data came from a survey of
      385 Chinese Americans aged 55 and older (Mage = 72.4 years, SD = 8.7) living in a
      large metropolitan area in the American Southwest. The survey was administered in
      2013 through face-to-face interviews. Depressive symptoms were assessed with the
      12-item Center for Epidemiological Studies Depression scale. Results:
      Approximately 19.5% of the sample reported mild depressive symptoms and an
      additional 8.5% reported moderate depressive symptoms. Three-step hierarchical
      regression analyses indicated that smaller family support network size and more
      family conflict were risk factors for depressive symptoms. The effect of
      acculturation was not significantly associated with depressive symptoms after
      controlling for family dynamics. Discussion: Family support and conflict play a
      prominent role in explaining depressive symptoms among Chinese American older
      adults. The effect of acculturation is minimal when older adults have supportive
      families and good health. Interventions or services aimed at promoting family
      harmony for members of this population should be considered.

PMID- 27048567
TI  - Work Impact and Emotional Stress Among Informal Caregivers for Older Adults.
AB  - Objectives: With the growing aging population and reliance on informal caregivers
      in the United States, many individuals will take on the role of caregiver as an
      adult. We examined whether informal caregivers experience work interference or a
      change in work status (i.e., retiring/quitting) due to caregiving. We also
      explored whether experiencing work interference or a change in work status was
      associated with greater emotional stress. Method: This secondary analysis is
      drawn from the Fifth National Survey of Older Americans Act (OAA) program
      participants, which included 1,793 family caregivers. The present analysis is on
      caregivers of working age (18-64 years) providing care to another adult, which
      included 922 caregivers. Ordinal logit models were used to assess associations
      between experiencing work interference or a change in work status and emotional
      stress. Study weights were applied for all analyses. Results: At the time of the
      survey, more than half (52.9%) of caregivers were employed full- or part-time.
      Among nonworking caregivers (i.e., not working or retired) at the time of the
      survey, 39.8% responded that they had quit or retired early due to caregiving
      demands. Among employed caregivers, 52.4% reported that informal caregiving had
      interfered with their employment. Importantly, those respondents who reported
      work interference or a change in work status were more likely to report higher
      levels of emotional stress associated with caregiving demands. Discussion: These
      findings suggest the need to further explore work among informal caregivers and
      associations with emotional stress, as well as consider work-based policy
      approaches, organizational and/or societal, to support informal caregivers.

PMID- 27048569
TI  - Passive Suicide Ideation Among Older Adults in Europe: A Multilevel Regression
      Analysis of Individual and Societal Determinants in 12 Countries (SHARE).
AB  - OBJECTIVES: Passive suicide ideation (PSI) is common among older adults, but
      prevalences have been reported to vary considerably across European countries.
      The goal of this study was to assess the role of individual-level risk factors
      and societal contextual factors associated with PSI in old age. METHOD: We
      analyzed longitudinal data from the Survey of Health, Ageing, and Retirement in
      Europe (SHARE) on 6,791 community-dwelling respondents (75+) from 12 countries.
      Bayesian logistic multilevel regression models were used to assess variance
      components, individual-level and country-level risk factors. RESULTS: About 4% of
      the total variance of PSI was located at the country level, a third of which was
      attributable to compositional effects of individual-level predictors. Predictors
      for the development of PSI at the individual level were female gender,
      depression, older age, poor health, smaller social network size, loneliness,
      nonreligiosity, and low perceived control (R (2) = 25.8%). At the country level,
      cultural acceptance of suicide, religiosity, and intergenerational cohabitation
      were associated with the rates of PSI. DISCUSSION: Cross-national variation in
      old-age PSI is mostly attributable to individual-level determinants and
      compositional differences, but there is also evidence for contextual effects of
      country-level characteristics. Suicide prevention programs should be intensified
      in high-risk countries and attitudes toward suicide should be addressed in
      information campaigns.

PMID- 27048570
TI  - Trans-anethole concentrations in bogma raki.

PMID- 27048571
TI  - Effect of resveratrol analogue, DMU-212, on antioxidant status and apoptosis
      related genes in rat model of hepatocarcinogenesis.
AB  - The aim of the study was to examine whether antioxidant properties of 3,4,4',5
      tetramethoxystilbene (DMU-212) contribute to its anticarcinogenic activity and
      whether DMU-212 affects the expression of apoptosis-related genes. Two-stage
      model of hepatocarcinogenesis was used; male Wistar rats were challenged with N
      nitrosodiethylamine (NDEA), 200 mg/kg body weight (b.w.), intraperitoneal, then
      phenobarbital (PB) in drinking water (0.05%) was administered. Simultaneously,
      DMU-212 was given per os at a dose 20 or 50 mg/kg b.w. two times a week for 16
      weeks. DMU-212 caused a moderate decrease in hepatic thiobarbituric acid reactive
      substances and protein carbonyls concentration elevated in rats treated with
      NDEA/PB. The activity of antioxidant enzymes examined reduced by NDEA/PB
      treatment was not restored in rats coadministered with DMU-212. Effects of DMU
      212 on messenger RNA (mRNA) expression of antioxidant enzymes in rats challenged
      with NDEA/PB were diversified; no changes in their protein expression were noted
      in any of the groups. The expression of 17,000 genes was analyzed by
      Affymetrix(r) Rat Gene 1.1 ST Array; 15 apoptosis-related genes were selected and
      validated by RT-q PCR. The combined treatment with NDEA/PB and DMU-212 increased
      the mRNA level of some genes driving mitochondria-mediated apoptosis, whereas the
      mRNA expression of some anti-apoptotic genes triggering receptor-mediated
      apoptosis was reduced. The expression of genes encoding caspases-4, -8, -9, and 
      12 was also increased in rats treated with DMU-212. Although antioxidant effect
      of DMU-212 in rats challenged with NDEA/PB was moderate, its potential
      anticarcinogenic properties were demonstrated as evidenced by modulation of
      apoptosis-related genes.

PMID- 27048573
TI  - Growing up in care: the disempowerment and disenfranchisement of carers.

PMID- 27048572
TI  - Extracellular vesicles during Herpes Simplex Virus type 1 infection: an inquire.
AB  - Extracellular vesicles are defined as a heterogeneous group of vesicles that are
      released by prokaryotic to higher eukaryotic cells and by plant cells in an
      evolutionary conserved manner. The significance of these vesicles lies in their
      capacity to transfer selected cargo composed of proteins, lipids and nucleic
      acids to both recipient and parent cells and to influence various physiological
      and pathological functions. Microorganisms such as parasites, fungi and protozoa
      and even single cell organisms such as bacteria generate extracellular vesicles.
      In addition, several viruses have evolved strategies to hijack the extracellular
      vesicles for egress or to alter the surrounding environment. The thesis of this
      article is that: a) during HSV-1 infection vesicles are delivered from infected
      to uninfected cells that influence the infection; b) the cargo of these vesicles
      consists of viral and host transcripts (mRNAs, miRNAs and non-coding RNAs) and
      proteins including innate immune components, such as STING; and c) the viral
      vesicles carry the tetraspanins CD9, CD63 and CD81, which are considered as
      markers of exosomes. Therefore, we assume that the STING-carrying vesicles,
      produced during HSV-1 infection, are reminiscent to exosomes. The presumed
      functions of the exosomes released from HSV-1 infected cells include priming the
      recipient cells and accelerating antiviral responses to control the dissemination
      of the virus. This may be one strategy used by the virus to prevent the
      elimination by the host and establish persistent infection. In conclusion, the
      modification of the cargo of exosomes appears to be part of the strategy that HSV
      1 has evolved to establish lifelong persistent infections into the human body to
      ensure successful dissemination between individuals. 

PMID- 27048574
TI  - iTRAQ-based analysis of developmental dynamics in the soybean leaf proteome
      reveals pathways associated with leaf photosynthetic rate.
AB  - Photosynthetic rate which acts as a vital limiting factor largely affects the
      potential of soybean production, especially during the senescence phase. However,
      the physiological and molecular mechanisms that underlying the change of
      photosynthetic rate during the developmental process of soybean leaves remain
      unclear. In this study, we compared the protein dynamics during the developmental
      process of leaves between the soybean cultivar Hobbit and the high-photosynthetic
      rate cultivar JD 17 using the iTRAQ (isobaric tags for relative and absolute
      quantification) method. A total number of 1269 proteins were detected in the
      leaves of these two cultivars at three different developmental stages. These
      proteins were classified into nine expression patterns depending on the
      expression levels at different developmental stages, and the proteins in each
      pattern were also further classified into three large groups and 20 small groups
      depending on the protein functions. Only 3.05-6.53 % of the detected proteins
      presented a differential expression pattern between these two cultivars.
      Enrichment factor analysis indicated that proteins involved in photosynthesis
      composed an important category. The expressions of photosynthesis-related
      proteins were also further confirmed by western blotting. Together, our results
      suggested that the reduction in photosynthetic rate as well as chloroplast
      activity and composition during the developmental process was a highly regulated
      and complex process which involved a serial of proteins that function as
      potential candidates to be targeted by biotechnological approaches for the
      improvement of photosynthetic rate and production. 

PMID- 27048575
TI  - How to write a neurology case report.
AB  - Neurology case reports have a long history of transmitting important medical
      information across many generations for the improvement of patient care. Case
      reports contribute much to the physician's knowledge base from which treatment
      hypotheses and ideas form. Elements of a modern case report, as presented in the
      CARE (CAse REport) guidelines, include the abstract, introduction, case
      presentation, discussion, conclusion, patient's perspective, and consent
      statement. The sections are described here, as well as the application of CARE
      guidelines to a published neuromuscular case report. Writing case reports offer
      an ideal opportunity for neurologists to publish interesting case findings and
      carry on the tradition of neurologic case reporting. 

PMID- 27048576
TI  - Factors associated with sickness certification of injured workers by General
      Practitioners in Victoria, Australia.
AB  - BACKGROUND: Work-related injuries resulting in long-term sickness certification
      can have serious consequences for injured workers, their families, society,
      compensation schemes, employers and healthcare service providers. The aim of this
      study was to establish what factors potentially are associated with the type of
      sickness certification that General Practitioners (GPs) provide to injured
      workers following work-related injury in Victoria, Australia. METHODS: This was a
      retrospective population-based cohort study was conducted for compensation claims
      lodged by adults from 2003 to 2010. A logistic regression analysis was performed
      to assess the impact of various factors on the likelihood that an injured worker
      would receive an alternate/modified duties (ALT, n = 28,174) vs. Unfit for work
      (UFW, n = 91,726) certificate from their GP. RESULTS: A total of 119,900 claims
      were analysed. The majority of the injured workers were males, mostly age of 45
      54 years. Nearly half of the workers (49.9%) with UFW and 36.9% with ALT
      certificates had musculoskeletal injuries. The multivariate regression analysis
      revealed that for most occupations older men (55-64 years) were less likely to
      receive an ALT certificate, (OR = 0.86, (95%CI, 0.81 - 0.91)). Workers suffering
      musculoskeletal injuries or occupational diseases were nearly twice or three
      times at higher odds of receiving an ALT certificate when compared to fractures.
      Being seen by a GP experienced with workers' compensation increased the odds of
      receiving ALT certificate (OR = 1.16, (95%CI, 1.11 - 1.20)). Occupation and
      industry types were also important factors determining the type of certificate
      issued to the injured worker. CONCLUSIONS: This study suggests that specific
      groups of injured workers (i.e. older age, workers with mental health issues, in
      rural areas) are less likely to receive ALT certificates.

PMID- 27048577
TI  - Preface.

PMID- 27048578
TI  - Antibiotic susceptibility in Streptococcus pneumoniae, Haemophilus influenzae and
      Streptococcus pyogenes in Pakistan: a review of results from the Survey of
      Antibiotic Resistance (SOAR) 2002-15.
AB  - OBJECTIVES: To investigate changes in the antibiotic susceptibility of
      Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes from
      the Survey of Antibiotic Resistance (SOAR) in community-acquired respiratory
      tract infections (CA-RTIs) between 2002 and 2015 in Pakistan. METHODS: This is a
      review based on previously published studies from 2002-03, 2004-06 and 2007-09
      and also new data from 2014-15. Susceptibility was determined by Etest((r)) or
      disc diffusion according to CLSI and pharmacokinetic/pharmacodynamic (PK/PD)
      breakpoints. RESULTS: A total of 706 isolates from CA-RTIs comprising 381 S.
      pneumoniae, 230 H. influenzae and 95 S. pyogenes were collected between 2002 and
      2015 and tested against a range of antibiotics. Antibiotic resistance in S.
      pneumoniae rose steeply from 2002 to 2009, with isolates non-susceptible to
      penicillin and macrolides increasing from 10% to 34.1% and from 13%-14% to 29.7%,
      respectively. Susceptibility to amoxicillin/clavulanic acid (and by inference
      amoxicillin) remained between 99.4% and 100% from 2002 to 2015. Over the years,
      the prevalence of susceptibility to cefuroxime was 98%-100% among S. pneumoniae.
      Resistance in S. pneumoniae to some older antibiotics between 2007 and 2009 was
      high (86.8% for trimethoprim/sulfamethoxazole and 57.2% for tetracycline).
      Between 2002 and 2015, ampicillin resistance (beta-lactamase-positive strains)
      among H. influenzae has remained low (between 2.6% and 3.2%) and almost unchanged
      over the years (H. influenzae was not tested during 2004-06). For S. pyogenes
      isolates, macrolide resistance reached 22%; however, susceptibility to
      penicillin, amoxicillin/clavulanic acid and cefuroxime remained stable at 100%.
      CONCLUSIONS: In S. pneumoniae from Pakistan, there has been a clear reduction in
      susceptibility to key antibiotics since 2002, but not to amoxicillin/clavulanic
      acid (amoxicillin) or cefuroxime. However, susceptibility in H. influenzae has
      remained stable. Local antibiotic susceptibility/resistance data are essential to
      support informed prescribing for CA-RTIs and other infections.

PMID- 27048579
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2011-14 in the Democratic
      Republic of Congo, Ivory Coast, Republic of Senegal and Kenya.
AB  - OBJECTIVES: To assess antibiotic susceptibility of community-acquired respiratory
      tract isolates from Ivory Coast, Kenya, Democratic Republic of Congo (DRC) and
      Senegal in 2011-14. METHODS: Bacterial isolates were collected and MICs
      determined using Etest((r)) for all antibiotics except erythromycin, for which
      testing was by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and
      pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide
      interpretation, CLSI breakpoints were adjusted for incubation in CO2. RESULTS:
      Susceptibility to penicillin (using CLSI oral or EUCAST breakpoints) was low
      among isolates of Streptococcus pneumoniae from the DRC and Kenya (17.4% and 19%,
      respectively) but higher among isolates from the Ivory Coast (70%) and Senegal
      (85.7%). Penicillin susceptibility using CLSI iv breakpoints was higher in all
      countries, but still only 69.6% in the DRC. Macrolide susceptibility (based on
      CLSI erythromycin disc diffusion breakpoints) was also low in Kenya (~65%) but
      87%-100% elsewhere. Haemophilus influenzae were only collected in the DRC and
      Senegal, with beta-lactamase prevalence of 39% and 4%, respectively. Furthermore,
      beta-lactamase-negative ampicillin-resistant (BLNAR) isolates were found in DRC
      (four isolates, 17%), but only two isolates were found in Senegal (by EUCAST
      definition). Amoxicillin/clavulanic acid in vitro susceptibility was 73.9% in the
      DRC and 100% in Senegal based on CLSI breakpoints, but this reduced to 65.2% in
      the DRC when BLNAR rates were considered. Clarithromycin susceptibility was >95%
      in both countries. CONCLUSIONS: There was considerable variability in antibiotic
      susceptibility among the African countries participating in the surveillance
      programme. Thus, continued surveillance is necessary to track future changes in
      antibiotic resistance. Use of EUCAST versus CLSI breakpoints showed profound
      differences for cefaclor and ofloxacin against S. pneumoniae, with EUCAST showing
      lower susceptibility.

PMID- 27048580
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2012-14 in Thailand,
      India, South Korea and Singapore.
AB  - OBJECTIVES: To provide susceptibility data for community-acquired respiratory
      tract isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus
      influenzae and Moraxella catarrhalis collected in 2012-14 from four Asian
      countries. METHODS: MICs were determined using Etest((r)) for all antibiotics
      except erythromycin, which was evaluated by disc diffusion. Susceptibility was
      assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD)
      breakpoints. For macrolide/clindamycin interpretation, breakpoints were adjusted
      for incubation in CO2 where available. RESULTS: Susceptibility of S. pneumoniae
      was generally lower in South Korea than in other countries. Penicillin
      susceptibility assessed using CLSI oral or EUCAST breakpoints ranged from 21.2%
      in South Korea to 63.8% in Singapore. In contrast, susceptibility using CLSI
      intravenous breakpoints was much higher, at 79% in South Korea and ~95% or higher
      elsewhere. Macrolide susceptibility was ~20% in South Korea and ~50%-60%
      elsewhere. Among S. pyogenes isolates (India only), erythromycin susceptibility
      (~20%) was lowest of the antibiotics tested. In H. influenzae antibiotic
      susceptibility was high except for ampicillin, where susceptibility ranged from
      16.7% in South Korea to 91.1% in India. South Korea also had a high percentage
      (18.1%) of beta-lactamase-negative ampicillin-resistant isolates.
      Amoxicillin/clavulanic acid susceptibility for each pathogen (PK/PD high dose)
      was between 93% and 100% in all countries except for H. influenzae in South Korea
      (62.5%). CONCLUSIONS: Use of EUCAST versus CLSI breakpoints had profound
      differences for cefaclor, cefuroxime and ofloxacin, with EUCAST showing lower
      susceptibility. There was considerable variability in susceptibility among
      countries in the same region. Thus, continued surveillance is necessary to track
      future changes in antibiotic resistance.

PMID- 27048581
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2009-11 and 2013-14 in
      China.
AB  - OBJECTIVES: To compare antibiotic susceptibility of community-acquired
      respiratory bacteria in China during 2009-11 and 2013-14. METHODS: Susceptibility
      was determined by Etest((r)) (bioMerieux) or disc diffusion according to CLSI,
      EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints, except for
      azithromycin where Etest((r)) breakpoints (in CO2 incubation) were used in place
      of standard CLSI breakpoints. Statistical significance of differences in
      susceptibility across time periods was evaluated using Fisher's exact test.
      RESULTS: During 2009-11, 434 Streptococcus pneumoniae, 307 Haemophilus influenzae
      and 140 Moraxella catarrhalis were collected from eight centres and during 2013
      14, 208 S. pneumoniae, 185 H. influenzae and 80 M. catarrhalis were collected
      from five centres. Penicillin-non-susceptible isolates remained stable at ~66%
      over both time periods but susceptibility decreased significantly for
      amoxicillin/clavulanic acid (or amoxicillin) and cefaclor. For H. influenzae, the
      proportion of beta-lactamase-positive isolates and beta-lactamase-negative
      ampicillin-resistant strains (CLSI definition) was higher in 2013-14 (25.4% and
      7.0%, respectively) than in 2009-11 (16.3% and 3.6%, respectively), with
      decreased ampicillin and cephalosporin susceptibility. By 2009-11 and 2013-14,
      only amoxicillin/clavulanic acid (amoxicillin), levofloxacin, penicillin
      (intravenously) and chloramphenicol inhibited >70% of S. pneumoniae. During 2013
      14, M. catarrhalis showed increasing resistance, with cefaclor and levofloxacin
      susceptibility decreasing significantly. However, amoxicillin/clavulanic acid,
      cefuroxime and levofloxacin continued to inhibit >90% of isolates. CONCLUSIONS:
      On the whole, antimicrobial susceptibility decreased in China between 2009-11 and
      2013-14. In 2013-14, amoxicillin/clavulanic acid, levofloxacin and
      chloramphenicol were the most active antibacterial agents tested against
      community-acquired respiratory pathogens when assessed by CLSI, EUCAST or PK/PD
      breakpoints. Resistance to other antibacterials in China was generally high. Our
      data demonstrate the need to harmonize breakpoints for these pathogens.

PMID- 27048582
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in the Gulf
      States.
AB  - OBJECTIVES: To provide surveillance data on the susceptibility of community
      acquired respiratory tract isolates from four Gulf and Near East countries from
      2011 to 2013. METHODS: MICs were determined using Etests((r)) for all antibiotics
      evaluated except erythromycin, where testing was by disc diffusion.
      Susceptibility was assessed using CLSI, EUCAST and
      pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: Seven hundred and
      twenty-six respiratory isolates comprising 265 isolates of Streptococcus
      pneumoniae, 125 isolates of Streptococcus pyogenes and 336 isolates of
      Haemophilus influenzae were collected from Bahrain, Lebanon, Oman and the United
      Arab Emirates (UAE). Among S. pneumoniae, susceptibility to penicillin was low in
      the UAE and Bahrain. Macrolide susceptibility was ~45%-60% in the UAE and Oman
      but higher in Lebanon (73.7%) and Bahrain (84%-85%). Penicillin susceptibility
      using CLSI intravenous breakpoints was >85% in all countries. Antibiotic
      susceptibility of S. pneumoniae was lower in UAE and Oman. Among S. pyogenes
      isolates, resistance to erythromycin was highest in Oman (31.6%) but <20% in the
      other countries. In H. influenzae, susceptibility to most antibiotics was high,
      except for ampicillin in Lebanon (70.2%) and amoxicillin in Oman (95.4%). Lebanon
      also had a high percentage (14.9%) of beta-lactamase-positive isolates with non
      susceptibility to ampicillin. Amoxicillin/clavulanic acid susceptibility was >95%
      in all countries. Use of EUCAST versus CLSI breakpoints demonstrated profound
      differences for cefaclor and cefuroxime in S. pneumoniae and H. influenzae, with
      EUCAST showing lower susceptibility. CONCLUSIONS: There was considerable
      variability in susceptibility among countries in the same region. Thus, continued
      surveillance is necessary to track future changes in antibiotic resistance.

PMID- 27048583
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Ukraine.
AB  - OBJECTIVES: To determine the antibiotic susceptibility of respiratory isolates of
      Streptococcus pneumoniae and Haemophilus influenzae collected in 2011-13 from
      Ukraine. METHODS: MICs were determined by CLSI broth microdilution and
      susceptibility was assessed using CLSI, EUCAST and
      pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 134
      isolates of S. pneumoniae and 67 of H. influenzae were collected from eight sites
      in Ukraine. Overall, 87.3% of S. pneumoniae were penicillin susceptible by CLSI
      oral breakpoints and 99.3% by CLSI iv breakpoints. Susceptibility to
      amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin was 100%
      by CLSI and PK/PD breakpoints. Cephalosporin and macrolide susceptibility was
      >=95.5% and 88.1%, respectively using CLSI breakpoints.
      Trimethoprim/sulfamethoxazole was essentially inactive against pneumococci. Of
      the 67 H. influenzae tested, 4.5% were beta-lactamase positive and all H.
      influenzae were fully susceptible to amoxicillin/clavulanic acid, ceftriaxone,
      ciprofloxacin, cefixime and levofloxacin (all breakpoints). Cefuroxime
      susceptibility was 100% by CLSI but 73.1% by EUCAST and PK/PD breakpoints. A
      discrepancy was found in macrolide susceptibility between CLSI (~100%
      susceptible), EUCAST (22%-43% susceptible) and PK/PD (0%-22% susceptible)
      breakpoints. Trimethoprim/sulfamethoxazole was poorly active (59.7% susceptible).
      CONCLUSIONS: Generally, antibiotic resistance was low in respiratory pathogens
      from Ukraine. However, only amoxicillin/clavulanic acid (amoxicillin),
      ceftriaxone and levofloxacin were fully active against both species.
      Trimethoprim/sulfamethoxazole was the least active, particularly against S.
      pneumoniae. Some susceptibility differences were apparent between CLSI, EUCAST
      and PK/PD breakpoints, especially with macrolides against H. influenzae. These
      data suggest that further efforts are required to harmonize these international
      breakpoints. Future studies are warranted to monitor continued low resistance
      levels in Ukraine compared with other parts of Eastern Europe.

PMID- 27048584
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Turkey.
AB  - OBJECTIVES: Data are presented from the Survey of Antibiotic Resistance (SOAR)
      for respiratory tract infection pathogens collected in 2011-13 from Turkey.
      METHODS: MICs were determined using Etest((r)). Susceptibility was assessed using
      CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) interpretive criteria.
      RESULTS: Rates of antibiotic susceptibility were very low among 333 isolates of
      Streptococcus pneumoniae tested: penicillin 38% using CLSI (oral) and EUCAST
      breakpoints; erythromycin 51% using CLSI and EUCAST criteria; and cefuroxime
      64.6% using CLSI and PK/PD and 46.9% using EUCAST. Of the isolates, >90% were
      susceptible to amoxicillin/clavulanic acid, ceftriaxone (except using EUCAST
      criteria: 76%), levofloxacin and high-dose intravenous penicillin. Among 339
      Haemophilus influenzae isolates, 6.8% were beta-lactamase positive while 9.1%
      were beta-lactamase negative but ampicillin resistant (BLNAR) by CLSI (14.7% by
      EUCAST) criteria. Amoxicillin/clavulanic acid susceptibility was ~90% by CLSI
      (with or without BLNAR adjustment, EUCAST and high-dose PK/PD) but lower, at
      82.9%, by EUCAST with BLNAR adjustment. Levofloxacin susceptibility was 96% using
      all three breakpoints. Dramatic differences in rates of susceptibility, depending
      on the breakpoints used, were seen for cefaclor [94% by CLSI (86.4% BLNAR
      adjusted), 23% by PK/PD] and cefuroxime [97% by CLSI (89.1% BLNAR adjusted), 85%
      by PK/PD, 15% by EUCAST (13.0% BLNAR adjusted)]. Streptococcus pyogenes (n = 222)
      and Moraxella catarrhalis (n = 40) isolates remained highly susceptible to
      amoxicillin/clavulanic acid, cephalosporins and levofloxacin, with only
      erythromycin susceptibility dropping below 95% for S. pyogenes. CONCLUSIONS:
      Overall, amoxicillin/clavulanic acid and levofloxacin were the most active
      antibiotics based on all three breakpoints against these pathogens. Although
      susceptibility was not universally low in Turkey, high resistance rates were
      found in S. pneumoniae and, when using PK/PD and EUCAST breakpoints, in other
      respiratory pathogens.

PMID- 27048585
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2002-09 in Turkey.
AB  - OBJECTIVES: To investigate changes in antibiotic susceptibility of Streptococcus
      pneumoniae and Haemophilus influenzae from the Survey of Antibiotic Resistance
      (SOAR) in community-acquired respiratory tract infections (CA-RTIs) between 2002
      and 2009 in Turkey. METHODS: Previously published SOAR data were used for this
      analysis. MICs were determined using Etest((r)) gradient strips or disc
      diffusion. Susceptibility against a range of antimicrobial agents was assessed
      using CLSI breakpoints. RESULTS: A total of 900 S. pneumoniae isolates were
      analysed: 2002-03 (n = 75), 2004-05 (n = 301) and 2007-09 (n = 524). Four
      antibiotics were tested consistently throughout and three showed a statistically
      significant decrease in susceptibility (P < 0.0001): penicillin (74.7%
      susceptible in 2002-03; 67.8% in 2004-05; and 47.2% in 2007-09); cefaclor (85.3%
      in 2002-03; 78.7% in 2004-05; and 53.5% in 2007-09) and clarithromycin (85.3% in
      2002-03; 82.7% in 2004-05; and 61.9% in 2007-09). Susceptibility to
      amoxicillin/clavulanic acid did not significantly change (100% in 2002-03; 98.7%
      in 2004-05; and 97.7% in 2007-09). A total of 930 H. influenzae isolates were
      analysed: 2002-03 (n = 133), 2004-05 (n = 379) and 2007-09 (n = 418). Four
      antibiotics were also consistently tested: ampicillin, amoxicillin/clavulanic
      acid, clarithromycin and cefaclor. All showed >90% susceptibility, but only
      cefaclor susceptibility significantly reduced (P < 0.0001) over time (99.2% in
      2002-03; 96.3% in 2004-05; and 90.4% in 2007-09). CONCLUSIONS: In S. pneumoniae
      from Turkey, there has been a clear statistically significant reduction in
      susceptibility to key antibiotics since 2002, but not to amoxicillin/clavulanic
      acid (or amoxicillin). However, susceptibility in H. influenzae remained stable.
      Continued surveillance is required to monitor future changes in antibiotic
      susceptibility for CA-RTI bacteria.

PMID- 27048587
TI  - Tory MP attacks government for "entirely unreasonable" tactics in junior doctors'
      dispute.

PMID- 27048586
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2009-11 in Vietnam.
AB  - OBJECTIVES: To investigate the susceptibility of respiratory tract infection
      pathogens collected between 2009 and 2011 from the SOAR study in Vietnam.
      METHODS: MICs were determined using Etest((r)) and susceptibility was assessed
      using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.
      RESULTS: Two hundred and eighty-nine Streptococcus pneumoniae and 195 Haemophilus
      influenzae were collected from 11 centres. Overall, 4.8% of S. pneumoniae were
      penicillin susceptible (CLSI oral and EUCAST breakpoints). Using CLSI intravenous
      breakpoints, 86.9% were penicillin susceptible. Susceptibility to high-dose
      amoxicillin/clavulanic acid (or amoxicillin) using PK/PD breakpoints, cefuroxime
      (using CLSI or PK/PD breakpoints), cefaclor (CLSI breakpoint) and azithromycin
      (CLSI breakpoint) was 96.9%, 18.7%, 8% and 4.2%, respectively. Ofloxacin
      susceptibility was 93.4% by CLSI but 0% by EUCAST. All S. pneumoniae were fully
      vancomycin susceptible. S. pneumoniae from children were significantly less
      susceptible to most antimicrobials than those from the elderly. For ofloxacin,
      however, the reverse was true.Among H. influenzae isolates, 40.5% produced beta
      lactamase and 13.8% were beta-lactamase negative but ampicillin resistant (BLNAR)
      by CLSI. H. influenzae were highly susceptible (97.4%) in vitro to
      amoxicillin/clavulanic acid and also to ceftriaxone by CLSI and PK/PD breakpoints
      but not EUCAST breakpoints. However, BLNAR isolates should be considered
      clinically resistant, with susceptibility reduced to 84.1%. With EUCAST
      breakpoints, amoxicillin/clavulanic acid susceptibility was lower, at 63.1%.
      Azithromycin susceptibility was 79.5% (CLSI). CONCLUSIONS: Resistance to
      antibacterials in Vietnam was high, with amoxicillin/clavulanic acid being the
      most active agent. Ceftriaxone was highly active against H. influenzae while
      ofloxacin appeared highly active against S. pneumoniae using CLSI but not by
      EUCAST breakpoints. Ongoing surveillance through SOAR will further assist in
      understanding susceptibility trends over time.

PMID- 27048588
TI  - Functional Status Predicts Awareness in Late-Onset but not in Early-Onset
      Alzheimer Disease.
AB  - This study aims to assess whether there are differences between the level of
      awareness in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer
      disease (LOAD) and to test its association with quality of life (QOL). A
      consecutive series of 207 people with Alzheimer disease and their caregivers were
      selected from an outpatient unit. There were no significant differences in
      awareness. In LOAD, impairment on awareness was predicted by functional level
      (beta = .37, P < .001), self ( P = .006), and informant report of QOL ( P =
      .010). The predictors of unawareness in EOAD were self ( P = .002) and informant
      report of QOL ( P < .001). There is a specific profile of functional deficits
      underlying awareness in people with LOAD. Additionally, reports of EOAD QOL were
      more strongly related to awareness than in people with LOAD.

PMID- 27048589
TI  - ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric
      cancer cells by inducing Siah2.
AB  - Helicobacter pylori infection is one of the most potent factors leading to
      gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3
      ubiquitin ligase which has been implicated in various cancers but its role in H.
      pylori-mediated gastric carcinogenesis has not been established. We investigated
      the involvement of Siah2 in gastric cancer metastasis which was assessed by
      invasiveness and migration of H. pylori-infected gastric epithelial cancer cells.
      Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly
      induced expression of Siah2, increased invasiveness and migration after being
      challenged with the pathogen. Siah2-expressing stable cells showed increased
      invasiveness and migration after H. pylori infection. Siah2 was transcriptionally
      activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related
      protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These
      transcription factors dose-dependently enhanced the aggressiveness of infected
      GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and
      invasiveness through Siah2 induction. As gastric cancer biopsy samples also
      showed highly induced expression of ETS2, Twist1 and Siah2 compared with
      noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up
      regulation has potential diagnostic and prognostic significance and could be
      targeted for therapeutic purpose.

PMID- 27048590
TI  - Role of post-translational modifications at the beta-subunit ectodomain in
      complex association with a promiscuous plant P4-ATPase.
AB  - P-type ATPases of subfamily IV (P4-ATPases) constitute a major group of
      phospholipid flippases that form heteromeric complexes with members of the Cdc50
      (cell division control 50) protein family. Some P4-ATPases interact specifically
      with only one beta-subunit isoform, whereas others are promiscuous and can
      interact with several isoforms. In the present study, we used a site-directed
      mutagenesis approach to assess the role of post-translational modifications at
      the plant ALIS5 beta-subunit ectodomain in the functionality of the promiscuous
      plant P4-ATPase ALA2. We identified two N-glycosylated residues, Asn(181) and
      Asn(231) Whereas mutation of Asn(231) seems to have a small effect on P4-ATPase
      complex formation, mutation of evolutionarily conserved Asn(181) disrupts
      interaction between the two subunits. Of the four cysteine residues located in
      the ALIS5 ectodomain, mutation of Cys(86) and Cys(107) compromises complex
      association, but the mutant beta-subunits still promote complex trafficking and
      activity to some extent. In contrast, disruption of a conserved disulfide bond
      between Cys(158) and Cys(172) has no effect on the P4-ATPase complex. Our results
      demonstrate that post-translational modifications in the beta-subunit have
      different functional roles in different organisms, which may be related to the
      promiscuity of the P4-ATPase.

PMID- 27048591
TI  - Non-canonical dynamic mechanisms of interaction between the p66Shc protein and
      Met receptor.
AB  - Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein
      isoforms encoded by the ShcA (Shc) gene. Structure-function studies have unveiled
      critical roles for p52Shc-dependent signalling pathways in Met-regulated
      biological functions. The molecular basis of the interaction between the Met and
      p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc.
      In the present study, co-immunoprecipitation assays were performed in human
      embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and
      p66Shc mutants, in order to define the molecular determinants involved in
      mediating Met-p66Shc interaction. Our results show that p66Shc interacts
      constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound
      protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its
      phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate
      p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding
      modules, and its collagen homology domain 2 (CH2) region, exert negative
      constraints. In contrast, p66Shc interaction with the activated Met depends
      mainly on the integrity of its PTB domain, and to a lesser extent of its SH2
      domain. Even though not required for the recruitment of p66Shc, tyrosine
      phosphorylation of p66Shc by activated Met enhances these interactions by
      mechanisms not reliant on the integrity of the Met multisubstrate-binding site.
      In turn, this increases phosphotyrosine-dependent p66Shc-Grb2-Gab1 complex
      formation away from the receptor, while blocking Grb2 and Gab1 recruitment to
      activated Met. In conclusion, we identify, for the first time, a novel non
      canonical dynamic mode of interaction between Met and the p66 protein isoform of
      Shc and its effects on rewiring binding effector complexes according to the
      activation state of the receptor.

PMID- 27048592
TI  - Nucleocytoplasmic human O-GlcNAc transferase is sufficient for O-GlcNAcylation of
      mitochondrial proteins.
AB  - O-linked N-acetylglucosamine modification (O-GlcNAcylation) is a nutrient
      dependent protein post-translational modification (PTM), dynamically and
      reversibly driven by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase
      (OGA) that catalyse the addition and the removal of the O-GlcNAc moieties to/from
      serine and threonine residues of target proteins respectively. Increasing
      evidence suggests involvement of O-GlcNAcylation in many biological processes,
      including transcription, signalling, neuronal development and mitochondrial
      function. The presence of a mitochondrial O-GlcNAc proteome and a mitochondrial
      OGT (mOGT) isoform has been reported. We explored the presence of mOGT in human
      cell lines and mouse tissues. Surprisingly, analysis of genomic sequences
      indicates that this isoform cannot be expressed in most of the species analysed,
      except some primates. In addition, we were not able to detect endogenous mOGT in
      a range of human cell lines. Knockdown experiments and Western blot analysis of
      all the predicted OGT isoforms suggested the expression of only a single OGT
      isoform. In agreement with this, we demonstrate that overexpression of the
      nucleocytoplasmic OGT (ncOGT) isoform leads to increased O-GlcNAcylation of
      mitochondrial proteins, suggesting that ncOGT is necessary and sufficient for the
      generation of the O-GlcNAc mitochondrial proteome.

PMID- 27048594
TI  - Authors' reply to Toth.

PMID- 27048593
TI  - Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric
      cancer cells.
AB  - Septins are a family of cytoskeletal GTP-binding proteins that assemble into
      membrane-associated hetero-oligomers and organize scaffolds for recruitment of
      cytosolic proteins or stabilization of membrane proteins. Septins have been
      implicated in a diverse range of cancers, including gastric cancer, but the
      underlying mechanisms remain unclear. The hypothesis tested here is that septins
      contribute to cancer by stabilizing the receptor tyrosine kinase ErbB2, an
      important target for cancer treatment. Septins and ErbB2 were highly over
      expressed in gastric cancer cells. Immunoprecipitation followed by MS analysis
      identified ErbB2 as a septin-interacting protein. Knockdown of septin-2 or cell
      exposure to forchlorfenuron (FCF), a well-established inhibitor of septin
      oligomerization, decreased surface and total levels of ErbB2. These treatments
      had no effect on epidermal growth factor receptor (EGFR), emphasizing the
      specificity and functionality of the septin-ErbB2 interaction. The level of
      ubiquitylated ErbB2 at the plasma membrane was elevated in cells treated with
      FCF, which was accompanied by a decrease in co-localization of ErbB2 with septins
      at the membrane. Cathepsin B inhibitor, but not bafilomycin or lactacystin,
      prevented FCF-induced decrease in total ErbB2 by increasing accumulation of
      ubiquitylated ErbB2 in lysosomes. Therefore, septins protect ErbB2 from
      ubiquitylation, endocytosis and lysosomal degradation. The FCF-induced
      degradation pathway is distinct from and additive with the degradation induced by
      inhibiting ErbB2 chaperone Hsp90. These results identify septins as novel
      regulators of ErbB2 expression that contribute to the remarkable stabilization of
      the receptor at the plasma membrane of cancer cells and may provide a basis for
      the development of new ErbB2-targeting anti-cancer therapies.

PMID- 27048595
TI  - The multiple aims of pay-for-performance and the risk of unintended consequences.

PMID- 27048596
TI  - Effect of diphenyl diselenide diet supplementation on oxidative stress biomarkers
      in two species of freshwater fish exposed to the insecticide fipronil.
AB  - The ability of diphenyl diselenide [(PhSe)2] to attenuate oxidative damage was
      evaluated in the liver, gills, brain, and muscle of carp (Cyprinus carpio) and
      silver catfish (Rhamdia quelen) experimentally exposed to fipronil (FPN).
      Initially, the fish were fed a diet without (PhSe)2 or a diet containing 3.0
      mg/kg of (PhSe)2 for 60 days. After the 60-day period, the fish were exposed to
      0.65 ug/L of FPN for 192 h. The results showed that carp exposed to FPN and not
      fed with (PhSe)2 exhibited acetylcholinesterase (AChE) inhibition in brain and
      muscle, and increased thiobarbituric acid-reactive substance (TBARS) in liver,
      gills, and brain. Furthermore, FPN decreased nonprotein thiols (NPSH) and delta
      aminolevulinate dehydratase (delta-ALA-D) in carp liver and gills, and increased
      plasma glucose and protein levels. In silver catfish, FPN inhibited AChE and
      increased TBARS levels in muscle. In addition, glutathione S-transferase (GST)
      decreased in liver and muscle, and plasma glucose was increased. (PhSe)2 reversed
      some of these effects. It prevented the increase in TBARS levels in liver, gills,
      and brain in carp and in silver catfish muscle, and reversed the increase in
      plasma glucose levels in both species. Additionally, (PhSe)2 increased the NPSH
      levels in carp and silver catfish that had decreased in response to FPN exposure.
      However, (PhSe)2 was not effective in reversing the AChE inhibition in brain and
      muscle or the delta-ALA-D decrease in carp liver. Thus, (PhSe)2 protects tissues
      of both species of fish, mainly by preventing or counteracting the effects of
      FPN, on TBARS levels, antioxidants, and present anti-hyperglycemic property. 

PMID- 27048597
TI  - Cloning and characterization of Bax1 and Bax2 genes of Ctenopharyngodon idellus
      and evaluation of transcript expression in response to grass carp reovirus
      infection.
AB  - Multidomain proapoptotic Bcl-2-associated X (Bax) protein is an essential
      effector responsible for mitochondrial outer membrane permeabilization, resulting
      in cell death via apoptosis. In this study, two Bax genes of grass carp
      (Ctenopharyngodon idellus), designated as CiBax1 and CiBax2, were isolated and
      analyzed. The obtained CiBax1 cDNA is 2058 bp long, with a 579 bp open reading
      frame (ORF) coding a protein of 192 amino acid residues. The full-length cDNA of
      CiBax2 is 1161 bp, with a 618 bp ORF coding 205 amino acids. Both CiBax1 and
      CiBax2 are typical members of Bcl-2 family containing conserved Bcl and C
      terminal domains, and they share conserved synteny with zebrafish Bax genes
      despite the grass carp Bax mapping to different linkage groups. Phylogenetic
      analysis showed that CiBax1 was clustered with Bax from most teleost fish, and
      CiBax2 was close to Bax2 from teleost fish but far separated from that of Salmo
      salar. Quantitative real-time PCR analysis revealed broad expression of CiBax1
      and CiBax2 in tissues from healthy grass carp, but the relative expression level
      differed. The mRNA expression of CiBax1 and CiBax2 was both upregulated
      significantly and peaked in all examined tissues at days 5 or 6 post-infection
      with grass carp reovirus. Subcellular localization indicated that CiBax1 protein
      was localized in both nucleus and cytosol, while CiBax2 protein only in cytosol.
      Moreover, CiBax2, but not CiBax1 was colocalized with mitochondrion under normal
      condition. Taken together, the findings would be helpful for further
      understanding of the function of Bax in teleost fish. 

PMID- 27048598
TI  - Load and failure behavior of human muscle samples in the context of proximal
      femur replacement.
AB  - BACKGROUND: To ensure adequate function after orthopedic tumor reconstruction, it
      is important to reattach the remaining soft tissue to the implant. This study
      aimed at obtaining mechanical properties of textile muscle-implant and muscle
      bone connections in a preliminary test. METHODS: Two groups of soft-tissue
      attachment were mechanically tested and compared: Native bone-muscle samples
      obtained from human femora and muscles attached to a prosthetic implant by means
      of Trevira(r) attachment tubes. Additionally, muscle samples were tested with
      muscle fibers aligned parallel and perpendicular to the tension load. A uniaxial
      load was exerted upon all samples. RESULTS: Failure loads of 26.7 +/- 8.8 N were
      observed for the native bone-muscle group and of 18.1 +/- 9.9 N for the
      Trevira(r) group. Elongations of 94.8 +/- 36.2 % were observed for the native
      bone-muscle group and 79.3 +/- 51.8 % for the Trevira(r) group. The location of
      failure was mainly observed in the central area of the muscle fibers. Muscle
      fibers with parallel fiber orientation (47.6 +/- 11.5 N) yielded higher tensile
      strength than those with perpendicular fiber orientation (14.8 +/- 4.1 N).
      CONCLUSIONS: Our experiments showed that higher forces were transmitted in the
      origin and insertion areas than in areas of flat soft tissue reconstruction using
      attachment tubes. The data indicate that the tested material allows reattaching
      muscles, but without reinforcing the insertion site. Therefore, attachment tubes
      with region-dependent and potentially anisotropic material behavior might be
      advantageous to optimize muscle-bone load transmission after surgery, which may
      allow lower complication rates and shorter physical recovery.

PMID- 27048599
TI  - BMA urges government to return to junior contract negotiations.

PMID- 27048600
TI  - De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities
      and dysmorphic features.
AB  - Whole exome sequencing (WES) can be used to efficiently identify de novo genetic
      variants associated with genetically heterogeneous conditions including
      intellectual disabilities. We have performed WES for 4102 (1847 female; 2255
      male) intellectual disability/developmental delay cases and we report five
      patients with a neurodevelopmental disorder associated with developmental delay,
      intellectual disability, behavioral problems, hypotonia, speech problems,
      microcephaly, pachygyria and dysmorphic features in whom we have identified de
      novo missense and canonical splice site mutations in CSNK2A1, the gene encoding
      CK2alpha, the catalytic subunit of protein kinase CK2, a ubiquitous
      serine/threonine kinase composed of two regulatory (beta) and two catalytic
      (alpha and/or alpha') subunits. Somatic mutations in CSNK2A1 have been implicated
      in various cancers; however, this is the first study to describe a human
      condition associated with germline mutations in any of the CK2 subunits.

PMID- 27048601
TI  - Characteristics of body composition and cardiometabolic risk of Japanese male
      heavyweight Judo athletes.
AB  - BACKGROUND: The purpose of this study was to clarify the characteristics of body
      composition and cardiometabolic risk of Japanese male heavyweight Judo athletes
      compared with heavyweight athletes of other sports. METHODS: Nineteen heavyweight
      Judo athletes (mean age, 20.4 +/- 1.1 years), as well as 22 heavyweight (mean
      age, 21.5 +/- 0.9 years) and 17 nonheavyweight (mean age, 21.1 +/- 0.8 years)
      American football and Rugby football athletes in Japan participated in this
      study. Body composition was assessed by using dual-energy X-ray absorptiometry
      and magnetic resonance imaging. Cardiometabolic risk was evaluated by measuring
      blood biochemical variables. RESULTS: Heavyweight Judo athletes had significantly
      heavier body mass (122.7 +/- 13.1 kg vs. 99.0 +/- 8.1 kg), higher body fat
      percentage (27.5 % +/- 5.2% vs. 19.4% +/- 4.7%), and larger visceral fat cross
      sectional area (118 +/- 35 cm(2) vs. 67 +/- 24 cm(2)) (P < 0.01) compared with
      heavyweight football players. Although the cardiometabolic risk was higher in
      heavyweight athletes compared to nonheavyweight athletes, there were no
      significant differences between heavyweight Judo and heavyweight Football
      athletes in the blood biochemical variables, except for high concentration of
      uric acid in heavyweight Judo athletes. CONCLUSIONS: Even though heavyweight Judo
      athletes had more excess fat mass, especially VF mass, their cardiometabolic risk
      in terms of blood biochemical parameters was not significantly higher compared
      with heavyweight athletes of other sports. Therefore, excessive fat accumulation
      may not necessarily increase cardiometabolic risk for heavyweight Judo athletes.
      TRIAL REGISTRATION: This trial is registered with the University Hospital Medical
      Information Network Clinical Trial Registration (UMIN-CTR) UMIN000020564.

PMID- 27048602
TI  - Stem cells and bFGF in tendon healing: Effects of lentiviral gene transfer and
      long-term follow-up in a rat Achilles tendon defect model.
AB  - BACKGROUND: The influence of stem cells and lentiviral expression of basic
      fibroblastic growth factor (bFGF) on tendon healing and remodelling was
      investigated in an in-vivo long-term (12 weeks) rat Achilles tendon defect model.
      METHODS: In sixty male Lewis rats, complete tendon defects (2.4 mm) were created
      and either left untreated (PBS) or treated by injection of stem cells
      lentivirally expressing the enhanced green fluorescence marker gene eGFP (MSC-LV
      eGFP) or basic fibroblast growth factor bFGF (MSC-LV-bFGF). Tendons were
      harvested after 12 weeks and underwent biomechanical and (immuno)-histological
      analysis. RESULTS: After 12 weeks the mean ultimate load to failure ratio
      (treated side to contralateral side) in biomechanical testing reached 97 % in the
      bFGF-group, 103 % in the eGFP-group and 112 % in the PBS-group. Also in the
      stiffness testing both MSC groups did not reach the results of the PBS group.
      Histologically, the MSC groups did not show better results than the control
      group. There were clusters of ossifications found in all groups. In
      immunohistology, only the staining collagen-type-I was strongly increased in both
      MSC groups in comparison to PBS control group. However, there were no significant
      differences in the (immuno)-histological results between both stem cell groups.
      CONCLUSION: The biomechanical and (immuno)-histological results did not show
      positive effects of the MSC groups on tendon remodelling in a long-term follow
      up. Interestingly, in later stages stem cells had hardly any effects on
      biomechanical results. This study inspires a critical and reflected use of stem
      cells in tendon healing.

PMID- 27048603
TI  - General self-efficacy and posttraumatic stress after a natural disaster: a
      longitudinal study.
AB  - BACKGROUND: Self-efficacy may be an important factor in individuals' recovery
      from posttraumatic stress reactions after a natural disaster. However, few
      longitudinal studies have investigated whether self-efficacy predicts the course
      of posttraumatic recovery beyond lower initial levels of distress. The purpose of
      the present study was to investigate whether general self-efficacy is related to
      recovery from posttraumatic stress reactions from a longitudinal perspective.
      METHODS: A total of 617 Norwegians exposed to the 2004 Southeast Asian tsunami
      completed self-report questionnaires measuring their level of disaster exposure
      and general self-efficacy at 6 months and posttraumatic stress reactions 6 months
      and 2 years post-disaster. Predictors of changes in posttraumatic stress
      reactions were analyzed with multivariate mixed effects models. RESULTS: Self
      efficacy at 6 months post-disaster was unrelated to trauma exposure and inversely
      related to posttraumatic stress reactions at 6 months and 2 years post-disaster.
      However, self-efficacy was not related to recovery from posttraumatic stress
      reactions between 6 months and 2 years post-disaster. CONCLUSIONS: In conclusion,
      general self-efficacy is related to lower levels of posttraumatic stress
      reactions in the first months after a disaster but does not appear to be related
      to improved recovery rates over the longer term.

PMID- 27048604
TI  - 28 day post-operative persisted hypercoagulability after surgery for benign
      diseases: a prospective cohort study.
AB  - BACKGROUND: Surgery for benign disease is associated with a low-risk of
      developing venous thromboembolism (VTE). Despite a relatively low incidence of
      postoperative VTE in patients after elective cholecystectomy and abdominal hernia
      repair there are data proving hypercoagulability in the early postoperative
      period. We focused on assessment of the systemic inflammatory response and
      coagulation status in these surgical patients after hospital discharge. METHODS:
      Prospectively, patients who underwent surgery for benign disease were included.
      Two hundred sixteen patients were enrolled - 90 patients in laparoscopic
      cholecystectomy (LC) group and 126 patients in hernia surgery (HS) group. Risk
      assessment of VTE according to the Caprini risk assessment model was performed in
      all patients. Prevalence of VTE in postoperative period was observed. Markers of
      systemic inflammatory response (IL-6, CRP, alpha-1-acid glycoprotein,
      transferrin) and coagulation markers (PLT, fibrinogen, prothrombin fragment F1 +
      2 and D-dimer) were measured before surgery, on 7-10th postoperative day and on
      28-30th postoperative day. RESULTS: Clinically apparent deep vein thrombosis was
      diagnosed in only one patient - 0.46%. Statistically significant elevation of
      inflammatory markers IL-6, CRP and alpha-1-acid glycoprotein (p < 0.001; all)
      were proved in both groups of patients on 7-10th postoperative day. Statistically
      significant elevation of coagulation markers PLT, fibrinogen, prothrombin
      fragment F1 + 2 and D-dimer (p < 0.001; all) were proved in LC and HS groups on 7
      10th postoperative day. No statistical difference was observed in IL-6, CRP and
      alpha-1-acid glycoprotein levels a month after surgery as compared with
      preoperative levels within each group. Statistically significant elevation of
      fibrinogen and prothrombin fragment F1 + 2 levels (p < 0.001; both) persisted on
      28-30th postoperative day in both groups. Persisted elevation of D-dimer levels
      was proved only in HS group (p < 0.001), not in LC group (p = 0.138), a month
      after surgery. CONCLUSIONS: Activated systemic inflammatory response and
      hypercoagulable condition were verified in patients after laparoscopic
      cholecystectomy and hernia surgery after their hospital discharge.
      Hypercoagulability persisted even a month after surgery. Nevertheless, we
      observed very low prevalence of clinically apparent VTE in patients with in
      hospital postoperative VTE prophylaxis. TRIAL REGISTRATION: Trials of the Czech
      Ministry of Health No. RVO-VFN64165 and NT 13251-4 .

PMID- 27048605
TI  - How ARDS should be treated.
AB  - The Berlin definition criteria applied at positive end-expiratory pressure (PEEP)
      5 cm H2O reasonably predict lung edema and recruitabilty. To maintain viable gas
      exchange, the mechanical ventilation becomes progressively more risky going from
      mild to severe acute respiratory distress syndrome (ARDS). Tidal volume, driving
      pressure, flow, and respiratory rate have been identified as causes of
      ventilation-induced lung injury. Taken together, they represent the mechanical
      power applied to the lung parenchyma. In an inhomogeneous lung, stress risers
      locally increase the applied mechanical power. Increasing lung homogeneity by
      PEEP and prone position decreases the harm of mechanical ventilation,
      particularly in severe ARDS.

PMID- 27048607
TI  - A Manual by Any Other Name: Identifying Psychotherapy Manuals for Resident
      Training.

PMID- 27048608
TI  - Rural Mental Health: Technology, Collective Intelligence, and Community Soul.

PMID- 27048609
TI  - Geoffrey Keynes's Two-Fold Vision: Medical Savant-Connoisseur and Literary
      Bibliographer.
AB  - During the 1920s and 1930s, the British surgeon Geoffrey Keynes (1887-1982)
      treated breast cancer with radium instead of the hegemonic radical mastectomy,
      while vehemently attacking the "radicalists" for mutilating women. Keynes was
      also a leading bibliographer of literary figures from Sir Thomas Browne to
      William Blake through Jane Austen. This article argues that these endeavors did
      not inhabit separate worlds, but rather his bibliographic methods of collecting
      and sorting were deeply interwoven with his therapeutic practices and medical
      ways of knowing. The article also examines the profound influence his engagement
      with the works of William Blake had on his battle against the reigning medical
      orthodoxy and on the humanity of his relationship with his patients. It concludes
      that Keynes' story sheds light on a now distant medico-cultural world where
      literary studies, often centered on book collecting and critique, were not only
      highly valued, but were influential in guiding the vision and behavior of a
      number of physicians.

PMID- 27048606
TI  - Reconsidering first-line treatment for obstructive sleep apnea: a systematic
      review of the literature.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is typically recommended
      as first line therapy for obstructive sleep apnea, but the adherence rate of CPAP
      is problematic. This study's objective was to systematically review the
      literature relating to CPAP as first line therapy for OSA and compare it to
      surgical literature on the same topic. METHODS: A systematic review was conducted
      according to PRISMA guidelines, examining Medline-Ovid, Embase, and Pubmed
      databases. The primary search objective was to identify all papers reporting the
      results of (1) randomized clinical trials (RCT) of CPAP for the treatment of
      adults with OSA; and (2) both randomized and non-randomized clinical trials and
      case series on the surgical treatment of OSA in adults. A PhD-level
      biostatistician first screened papers, and then those that met study criteria
      were retrieved and analyzed using standardized forms for each author. The primary
      outcomes were adherence rates of CPAP. RESULTS: A total of 82 controlled clinical
      trials for CPAP and 69 controlled and non-controlled surgery trials were
      identified for analysis. Variation in CPAP use within reported RCT trials were
      identified, and the majority of patients in the studies would eventually be
      considered non-adherent to CPAP. CONCLUSIONS: When considering the numerous
      patient-related factors that come into play when CPAP is prescribed, the concept
      of CPAP as gold-standard therapy for OSA should be reconsidered. In many cases
      surgery can provide a better overall outcome. This study's results suggest that
      certain patients with OSA may be managed more effectively with surgery than CPAP,
      without confounding issues of treatment adherence.

PMID- 27048610
TI  - Easier Said Than Done: Keys to Successful Implementation of the Distress
      Assessment and Response Tool (DART) Program.
AB  - PURPOSE: Systematic screening for distress in oncology clinics has gained
      increasing acceptance as a means to improve cancer care, but its implementation
      poses enormous challenges. We describe the development and implementation of the
      Distress Assessment and Response Tool (DART) program in a large urban
      comprehensive cancer center. METHOD: DART is an electronic screening tool used to
      detect physical and emotional distress and practical concerns and is linked to
      triaged interprofessional collaborative care pathways. The implementation of DART
      depended on clinician education, technological innovation, transparent
      communication, and an evaluation framework based on principles of change
      management and quality improvement. RESULTS: There have been 364,378 DART surveys
      completed since 2010, with a sustained screening rate of > 70% for the past 3
      years. High staff satisfaction, increased perception of teamwork, greater
      clinical attention to the psychosocial needs of patients, patient-clinician
      communication, and patient satisfaction with care were demonstrated without a
      resultant increase in referrals to specialized psychosocial services. DART is now
      a standard of care for all patients attending the cancer center and a quality
      performance indicator for the organization. CONCLUSION: Key factors in the
      success of DART implementation were the adoption of a programmatic approach,
      strong institutional commitment, and a primary focus on clinic-based response. We
      have demonstrated that large-scale routine screening for distress in a cancer
      center is achievable and has the potential to enhance the cancer care experience
      for both patients and staff.

PMID- 27048611
TI  - Adolescents and Young Adult Cancer Trial Participation: Will the National
      Community Oncology Research Program Also Fail? And What About the Rest of Us?

PMID- 27048612
TI  - New Diagnosis Bundle: Improving Care Delivery for Patients With Newly Diagnosed
      Cancer.

PMID- 27048613
TI  - Reducing Unplanned Medical Oncology Readmissions by Improving Outpatient Care
      Transitions: A Process Improvement Project at the Cleveland Clinic.
AB  - PURPOSE: Reducing 30-day unplanned hospital readmissions is a national policy
      priority. We examined the impact of a quality improvement project focused on
      reducing oncology readmissions among patients with cancer who were admitted to
      palliative and general medical oncology services at the Cleveland Clinic.
      METHODS: Baseline rates of readmissions were gathered during the period from
      January 2013 to April 2014. A quality improvement project designed to improve
      outpatient care transitions was initiated during the period leading to April 1,
      2014, including: (1) provider education, (2) postdischarge nursing phone calls
      within 48 hours, and (3) postdischarge provider follow-up appointments within 5
      business days. Nursing callback components included symptom management,
      education, medication review/compliance, and follow-up appointment reminder.
      RESULTS: During the baseline period, there were 2,638 admissions and 722
      unplanned 30-day readmissions for an overall readmission rate of 27.4%. Callbacks
      and 5-day follow-up appointment monitoring revealed a mean monthly compliance of
      72% and 78%, respectively, improving over time during the study period.
      Readmission rates declined by 4.5% to 22.9% (P < .01; relative risk reduction,
      18%) during the study period. The mean direct cost of one readmission was
      $10,884, suggesting an annualized cost savings of $1.04 million with the observed
      reduction in unplanned readmissions. CONCLUSION: Modest readmission reductions
      can be achieved through better systematic transitions to outpatient care
      (including follow-up calls and early provider visits), thereby leading to a
      reduction in use of inpatient resources. These data suggest that efforts focused
      on improving outpatient care transition were effective in reducing unplanned
      oncology readmissions.

PMID- 27048614
TI  - Readmissions After Colon Cancer Surgery: Does It Matter Where Patients Are
      Readmitted?
AB  - PURPOSE: Readmissions to a different hospital may place patients at increased
      risk for poor outcomes and may increase their overall costs of care. We evaluated
      whether mortality and costs differ for patients with colon cancer on the basis of
      whether patients are readmitted to the index hospital or to a different hospital
      within 30 days of discharge. METHODS: We conducted a retrospective analysis using
      SEER-Medicare linked claims data for patients with stage I to III colon cancer
      diagnosed between 2000 and2009 who were readmitted within 30 days (N = 3,399).
      Our primary outcome was all-cause mortality, which was modeled by using Cox
      proportional hazards. Secondary outcomes included colon cancer-specific
      mortality, 90-day mortality, and costs of care. We used subhazard ratios for
      colon cancer- specific mortality and generalized linear models for costs. For
      each model, we used a propensity score-weighted doubly robust approach to adjust
      for patient, physician, and hospital characteristics. RESULTS: Approximately 23%
      (n = 769) of readmitted patients were readmitted to a different hospital than
      where they were initially discharged. After adjustment, there was no difference
      in all-cause mortality, colon cancer-specific mortality, or cost of care for
      patients readmitted to a different hospital. Patient readmitted to a different
      hospital did have a higher risk of short-term mortality (90-day all-cause
      mortality; adjusted hazard ratio, 1.18; 95% CI, 1.02 to 1.38). CONCLUSION:
      Readmission to a different hospital after colon cancer surgery is associated with
      short-term mortality but not with long-term mortality nor with post-discharge
      costs of care. Additional investigation is needed to determine how to improve
      short-term mortality among patients readmitted to different hospitals.

PMID- 27048615
TI  - Use of Survivorship Care Plans and Analysis of Patient-Reported Outcomes in
      Multinational Patients With Lung Cancer.
AB  - PURPOSE: Lung cancer is the leading cause of cancer death and is a significant
      source of morbidity. Patient-reported outcomes (PROs) have been shown to be
      prognostic for survival. We have analyzed emerging patterns of longitudinal PROs
      collected in the development of survivorship care plans (SCPs). METHODS: OncoLife
      and the LIVESTRONG Care Plans are Internet-based programs designed to generate
      unique SCPs. We selected SCPs from patients identifying as survivors of primary
      lung cancer. Patient-reported demographics and treatment and toxicity data were
      examined. Effects were categorized by the physiologic system that they affected.
      RESULTS: Six hundred eighty-nine plans were created for users self-identifying as
      survivors of primary lung cancer. Average time from diagnosis to reporting was
      1.68 years (range, 0 to 24 years). Most were white (85.9%), well educated (61.1%
      "some college" or higher), and lived in the United States (90.7%). Patients
      underwent chemotherapy (75.8%), radiotherapy (54.7%), and surgery (54.4%).
      Neurocognitive symptoms (eg, fatigue, cognitive changes) were the most common
      (48.8%), especially among those receiving chemotherapy, followed by
      musculoskeletal/dermatologic symptoms (14.1%) and thoracic symptoms (13.5%). Only
      11.2% were initially offered an SCP. Of those offered SCPs, 54.5% were offered by
      their health care provider, and most often were at a non-university-based cancer
      center (66.2%). CONCLUSION: For patients with lung cancer worldwide, it is
      feasible to obtain PROs and to create SCPs through an Internet-based program. As
      patients with lung cancer achieve improved survival, further attention should be
      paid to PROs. Surprisingly, neurocognitive symptoms seem to be the most common
      issues and therefore the most important to address. Increased effort should be
      made to provide SCPs, particularly in urban and university cancer center
      settings.

PMID- 27048616
TI  - Hepatitis C virus cell entry: a target for novel antiviral strategies to address
      limitations of direct acting antivirals.
AB  - Hepatitis C virus (HCV) infection remains a major global health problem, with 130
      170 million chronically infected individuals at risk to develop severe liver
      disease, including hepatocellular carcinoma. Although the development of direct
      acting antivirals offers cure for a large majority of patients, there are still a
      number of clinical challenges. These include DAA failure in a significant subset
      of patients, difficult-to-treat genotypes and limited access to therapy due to
      high costs. Moreover, recent data indicate that the risk for liver cancer
      persists in patients with advanced fibrosis. These challenges highlight the need
      for continued efforts towards novel therapeutic strategies for HCV. Over the past
      two decades, advances in HCV model systems have enabled a detailed understanding
      of HCV entry and its clinical impact. Many of the virus-host interactions
      involved in HCV entry have now been identified and explored as antiviral targets.
      Furthermore, viral entry is recognized as an important factor for graft
      reinfection and establishment of persistent infection. HCV entry inhibitors,
      therefore, offer promising opportunities to address the limitations of DAAs.
      Here, we summarize recent advances in the field of HCV entry and discuss
      perspectives towards the prevention and cure of HCV infection and virus-induced
      liver disease. 

PMID- 27048617
TI  - The role of bile salts in liver regeneration.
AB  - A growing body of evidence has demonstrated that bile salts are important for
      liver regeneration following partial hepatectomy. The relative bile salt overload
      after partial liver resection causes activation of bile salt receptors in non
      parenchymal (viz. the plasma membrane receptor TGR5) and parenchymal (viz. the
      intracellular receptor FXR) cells in the liver, thus, providing signals to the
      regenerative process. Impaired bile salt signaling in mice with genetic
      deficiency of Tgr5 or Fxr results in delayed liver regeneration after partial
      hepatectomy, and is accompanied by mortality in case of Fxr knock-out mice.
      Conversely, compensatory liver re-growth in hepatectomized mice can be stimulated
      by feeding of bile salts or alisol B 23-acetate, a natural triterpenoid agonist
      of Fxr. A large number of animal studies underscore the importance of strict
      maintenance of bile salt homeostasis for proper progression of liver
      regeneration. Both ileal and hepatic Fxr play a key role in regulation of bile
      salt homeostasis and, thus, preventing hepatotoxicity caused by excessive levels
      of bile salts. They further contribute to liver regeneration by induction of
      mitogenic factors. Agents that target bile salt receptors hold promise as drugs
      to stimulate liver regeneration in selected patients. 

PMID- 27048618
TI  - Innovations in health information technologies for chronic pulmonary diseases.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are common chronic
      obstructive lung disorders in the US that affect over 49 million people. There is
      no cure for asthma or COPD, but clinical guidelines exist for controlling
      symptoms that are successful in most patients that adhere to their treatment
      plan. Health information technologies (HITs) are revolutionizing healthcare by
      becoming mainstream tools to assist patients in self-monitoring and decision
      making, and subsequently, driving a shift toward a care model increasingly
      centered on personal adoption and use of digital and web-based tools. While the
      number of chronic pulmonary disease HITs is rapidly increasing, most have not
      been validated as clinically effective tools for the management of disease.
      Online communities for asthma and COPD patients are becoming sources of
      empowerment and support, as well as facilitators of patient-centered research
      efforts. In addition to empowering patients and facilitating disease self
      management, HITs offer promise to aid researchers in identifying chronic
      pulmonary disease endotypes and personalized treatments based on patient-specific
      profiles that integrate symptom occurrence and medication usage with
      environmental and genomic data. 

PMID- 27048619
TI  - The history of Old World camelids in the light of molecular genetics.
AB  - Old World camels have come into the focus as sustainable livestock species,
      unique in their morphological and physiological characteristics and capable of
      providing vital products even under extreme environmental conditions. The
      evolutionary history of dromedary and Bactrian camels traces back to the middle
      Eocene (around 40 million years ago, mya), when the ancestors of Camelus emerged
      on the North American continent. While the genetic status of the two domestic
      species has long been established, the wild two-humped camel has only recently
      been recognized as a separate species, Camelus ferus, based on molecular genetic
      data. The demographic history established from genome drafts of Old World camels
      shows the independent development of the three species over the last 100,000
      years with severe bottlenecks occurring during the last glacial period and in the
      recent past. Ongoing studies involve the immune system, relevant production
      traits, and the global population structure and domestication of Old World
      camels. Based on the now available whole genome drafts, specific metabolic
      pathways have been described shedding new light on the camels' ability to adapt
      to desert environments. These new data will also be at the origin for genome-wide
      association studies to link economically relevant phenotypes to genotypes and to
      conserve the diverse genetic resources in Old World camelids. 

PMID- 27048621
TI  - Tuning the structure and solubility of nanojars by peripheral ligand
      substitution, leading to unprecedented liquid-liquid extraction of the carbonate
      ion from water into aliphatic solvents.
AB  - Nanojars, a novel class of neutral anion-incarcerating agents of the general
      formula [Cu(II)(OH)(pz)]n (Cun; n = 27-31, pz = pyrazolate anion), efficiently
      sequester various oxoanions with large hydration energies from water. In this
      work, we explore whether substituents on the pyrazole ligand interfere with
      nanojar formation, and whether appropriate substituents could be employed to tune
      the solubility of nanojars in solvents of interest, such as long-chain aliphatic
      hydrocarbons (solvent of choice for large-scale liquid-liquid extraction
      processes) and water. To this end, we conducted a comprehensive study using 40
      different pyrazole ligands, with one, two or three substituents in their 3-, 4-
      and 5-positions. The corresponding nanojars are characterized by single-crystal X
      ray diffraction and/or electrospray-ionization mass spectrometry (ESI-MS). The
      results show that Cun-nanojars with various substituents in the pyrazole 4
      position, including long chains, phenyl and CF3 groups, can be obtained. Straight
      chains are also tolerated at the pyrazole 3-position, and favor the Cu30-nanojar.
      Homoleptic nanojars, however, could not be obtained with phenyl or CF3 groups.
      Nevertheless, if used in mixture with the parent non-substituted pyrazole,
      sterically hindered pyrazoles do form heteroleptic nanojars. With 3,5
      disubstituted pyrazoles, only heteroleptic nanojars are accessible. The crystal
      structure of novel nanojars (Bu4N)2[CO3?{Cu30(OH)30(3,5-Me2pz)y(pz)30-y}] (y = 14
      and 15) is presented. We find that in contrast to the parent nanojar, which is
      insoluble in aliphatic solvents and water, nanojars with alkyl substituents are
      soluble in saturated hydrocarbon solvents, whereas nanojars based on novel
      pyrazoles, functionalized with oligoether chains, are readily soluble in water.
      Liquid-liquid extraction of carbonate from water under basic pH is presented for
      the first time. 

PMID- 27048620
TI  - Computational analysis of EBNA1 "druggability" suggests novel insights for
      Epstein-Barr virus inhibitor design.
AB  - The Epstein-Barr Nuclear Antigen 1 (EBNA1) is a critical protein encoded by the
      Epstein-Barr Virus (EBV). During latent infection, EBNA1 is essential for DNA
      replication and transcription initiation of viral and cellular genes and is
      necessary to immortalize primary B-lymphocytes. Nonetheless, the concept of EBNA1
      as drug target is novel. Two EBNA1 crystal structures are publicly available and
      the first small-molecule EBNA1 inhibitors were recently discovered. However, no
      systematic studies have been reported on the structural details of EBNA1
      "druggable" binding sites. We conducted computational identification and
      structural characterization of EBNA1 binding pockets, likely to accommodate
      ligand molecules (i.e. "druggable" binding sites). Then, we validated our
      predictions by docking against a set of compounds previously tested in vitro for
      EBNA1 inhibition (PubChem AID-2381). Finally, we supported assessments of pocket
      druggability by performing induced fit docking and molecular dynamics simulations
      paired with binding affinity predictions by Molecular Mechanics Generalized Born
      Surface Area calculations for a number of hits belonging to druggable binding
      sites. Our results establish EBNA1 as a target for drug discovery, and provide
      the computational evidence that active AID-2381 hits disrupt EBNA1:DNA binding
      upon interacting at individual sites. Lastly, structural properties of top
      scoring hits are proposed to support the rational design of the next generation
      of EBNA1 inhibitors.

PMID- 27048622
TI  - Psychiatric aspects of normal and pathological lying.
AB  - The paper outlines the difference between the so-called normal (common) lying and
      pathological lying. Pathological lying is an intriguing topic, still lacking any
      strong professional consensus, clear etiology, treatment options and prognoses.
      The paper explores some possible psychological mechanisms of pathological lying,
      reviews biological factors in pathological lying, and considers forensic
      significance of normal and pathological lying. The relationship between
      pathological lying and mental disorders is also discussed. The authors suggest
      that lying should be considered as a heterogenic and multidimensional behavioral
      pattern. The paper highlights how important it is to assess the patient's control
      over lying, the function of lying, insight into and awareness of lying, as well
      as the effect of lying on everyday functioning.

PMID- 27048623
TI  - Professional caregiver's knowledge of self-reported delinquency in an adolescent
      sample in Swiss youth welfare and juvenile justice institutions.
AB  - Since an important goal of the youth welfare system is to prevent troubled
      adolescents from committing acts of delinquency in future, professional
      caregivers need to possess accurate knowledge about past behaviors in order to
      implement appropriate interventions. As part of a comprehensive study on youth in
      state care, adolescents at 30 residential care facilities in Switzerland were
      surveyed about past acts of delinquency, and their responses were compared to
      those of their professional caregivers to see how well they correlated. A sample
      of 267 male and female adolescents aged 11-18years completed questionnaires about
      the frequency, nature, and seriousness of different types of offenses, while a
      designated caregiver for each resident completed a corresponding questionnaire.
      The majority of residents (86.1%) reported having committed at least one offense,
      which confirms the prevalence of problem behaviors in this population and the
      need for strategies to prevent it. The overall rate of agreement between the
      residents and their caregivers was 77.2%, with both parties reporting that the
      resident had committed at least one offense in 69.7% of cases, and both reporting
      that no offense had been committed in 7.5% of cases. Agreement was substantially
      higher for offenses that were serious than for those that were minor or moderate.
      Cohen's kappa reached slight to moderate values with regard to individual and
      categorized offenses. Seriousness scales of delinquency for self-reports and
      caregiver reports were moderately associated. While the overall rate of agreement
      between the residents and their caregivers was high, increasing it still further
      might lead to improvements in strategies for the prevention of recidivism.

PMID- 27048624
TI  - Astrocytes as a target for neuroprotection: Modulation by progesterone and
      dehydroepiandrosterone.
AB  - Stroke and traumatic injuries of the brain and spinal cord are major public
      health issues. In the last few decades, hundreds of clinical trials with patients
      suffering from these conditions have been done, however, most of them had not
      succeeded and there is still the need to develop more effective treatments for
      these conditions. Astrocytes play critical roles in the development, function and
      survival of neurons in the central nervous system. These cells are implicated in
      the pathophysiology and in the response to several neuropathological conditions
      and may represent potential cell targets for neuroprotective strategies.
      Progesterone and dehydroepiandrosterone (DHEA) are neuroactive steroids that
      modulate neuronal and astroglial function and have neuroprotective effects in
      different experimental models, being potential candidates to the development of
      new therapeutic approaches for brain and spinal cord injuries. The aim of this
      review is to discuss the role of astrocytes in the pathophysiology of brain and
      spinal cord injuries and how they could be modulated by progesterone and DHEA for
      the treatment of these conditions.

PMID- 27048625
TI  - Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.
AB  - BACKGROUND: Acute organophosphorus pesticide poisoning (AOPP) is becoming a
      significant problem and a potential cause of human mortality because of the abuse
      of organophosphate compounds. This study aims to determine the independent
      prognostic factors of AOPP by using multivariate logistic regression analysis.
      METHODS: The clinical data for 71 subjects with AOPP admitted to our hospital
      were retrospectively analyzed. This information included the Acute Physiology and
      Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate
      levels, post-admission 6-h lactate clearance rates, admission blood
      cholinesterase levels, 6-h post-admission blood cholinesterase levels,
      cholinesterase activity, blood pH, and other factors. Univariate analysis and
      multivariate logistic regression analyses were conducted to identify all
      prognostic factors and independent prognostic factors, respectively. A receiver
      operating characteristic curve was plotted to analyze the testing power of
      independent prognostic factors. RESULTS: Twelve of 71 subjects died. Admission
      blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h
      lactate clearance rates, blood pH, and APACHE II scores were identified as
      prognostic factors for AOPP according to the univariate analysis, whereas only 6
      h post-admission blood lactate levels, post-admission 6-h lactate clearance
      rates, and blood pH were independent prognostic factors identified by
      multivariate logistic regression analysis. The receiver operating characteristic
      analysis suggested that post-admission 6-h lactate clearance rates were of
      moderate diagnostic value. CONCLUSIONS: High 6-h post-admission blood lactate
      levels, low blood pH, and low post-admission 6-h lactate clearance rates were
      independent prognostic factors identified by multivariate logistic regression
      analysis.

PMID- 27048626
TI  - Mechanisms of Orthopnea in Stable Obese Subjects.
AB  - BACKGROUND: The present study explored the role of closing volume as a
      determinant of orthopnea in stable obese subjects. We hypothesized that: (1)
      increase in closing volume in supine position would be greater in orthopneic than
      in non-orthopneic subjects, and (2) the relationship of change in closing volume
      to change in dyspnea with position would be dependent on expiratory flow
      limitation in the sitting position. METHODS: In stable obese subjects, in sitting
      and supine positions, we measured the Borg dyspnea score, static lung volumes,
      expiratory flow limitation during tidal breathing, and single-breath nitrogen
      expiration test. From the latter, we determined closing volume and closing
      capacity, slope of phase III, and opening capacity. Orthopnea was defined as any
      increase in the Borg score in the supine position from its value in the sitting
      position. RESULTS: Twenty-one subjects (13 women), median age (interquartile
      range) 55 (49-57) y and with body mass index of 39 (38-42) kg/m(2) were included,
      of whom 12 were orthopneic and 11 had expiratory flow limitation while seated. In
      the sitting position, orthopneic and non-orthopneic subjects were similar for
      age, body mass index, and pulmonary function tests, including single-breath
      nitrogen expiration test-derived variables. In the orthopneic subjects, there
      were no changes in any respiratory variable between positions. In the non
      orthopneic subjects, there was a significant decrease in slope of phase III in
      the supine position from 1.67 (1.33-3.60) to 1.40 (1.25-1.66)%/L (P = .008).
      Overall, the subjects' Borg score significantly correlated with the slope of
      phase III (r = 0.63, P = .002) and opening capacity (r = -0.47, P = .03). In 10
      subjects without expiratory flow limitation, it correlated with slope of phase
      III (r = 0.68, P = .03). CONCLUSIONS: In stable obese subjects, magnitude of
      orthopnea correlated with an increase in the slope of phase III in subjects
      without expiratory flow limitation. Expiratory flow limitation should be taken
      into account in obese patients.

PMID- 27048627
TI  - Resistance of Colorimetric Carbon Dioxide Detectors Commonly Utilized in
      Neonates.
AB  - BACKGROUND: Colorimetric end-tidal carbon dioxide (ETCO2) detectors can identify
      airway obstruction during noninvasive ventilation and successful intubation
      during newborn resuscitation. The resistance of these devices is not well
      described, and the information provided by manufacturers is incomplete. METHODS:
      We compared the resistance of 3 colorimetric ETCO2 detectors (Neo-StatCO2, Pedi
      Cap, and Mini StatCO2,) and 2 mainstream capnograph sensors (EMMA infant airway
      adapter 17449 and neonatal/infant airway adapter YG-213T). Endotracheal tubes,
      2.5-4.0-mm inner diameter (Portex) were measured as a reference range. A
      differential pressure transducer was placed between the device and a T-piece
      resuscitator. The other side of the device was open to air. Resistance to flow
      was tested at 1-10 L/min. Resistance was calculated as the change in pressure
      over change in flow and expressed as cm H2O/L/s. RESULTS: There was a
      significantly higher mean resistance across all flows tested for the Neo-StatCO2
      compared with the other ETCO2 devices (P < .001). There was a 6-fold difference
      between the least and most resistive colorimetric detectors. At the commonly
      utilized flow of 10 L/min, the resistance of the Neo-StatCO2 was 61.1 cm H2O/L/s,
      comparable with that of a 3.0 endotracheal tube, which we measured at 62.7 cm
      H2O/L/s. The resistance values of the Pedi-Cap and Mini StatCO2 were 9.9 and 8.4
      cm H2O/L/s, respectively. Those of the EMMA and YG-213T were 7.1 and 2.6 cm
      H2O/L/s, respectively. CONCLUSIONS: We found significant differences in
      resistance between devices used to detect ETCO2 during resuscitation of premature
      infants. Future trials are needed to determine the effects of this resistance on
      work of breathing, particularly on very premature newborns receiving mask CPAP.

PMID- 27048628
TI  - Association of human leukocyte antigen alleles with chronic lung diseases in
      rheumatoid arthritis.
AB  - OBJECTIVES: Chronic lung diseases including interstitial lung disease and airway
      disease (AD) occur in RA patients. Interstitial lung disease and AD in RA are
      extra-articular manifestations that influence the prognosis quoad vitam of RA.
      Studies on associations of HLA alleles with RA have been carried out, and shared
      epitopes of several alleles are reported to be associated with RA susceptibility.
      Few association studies in RA subpopulations with chronic lung diseases have been
      conducted. The aim of the study was to identify HLA alleles predisposing to RA
      phenotypes including the presence of AD. METHODS: Associations of HLA-DRB1 and
      DQB1 alleles with chronic lung diseases in RA were analysed. RESULTS: A positive
      association was found between the DR4 serological group and resistance to usual
      interstitial pneumonia [P = 0.0250, odds ratio (OR) 0.62, 95% CI: 0.41, 0.93].
      The DR2 serological group was associated with susceptibility to usual
      interstitial pneumonia (P = 0.0036, OR = 1.86, 95% CI: 1.23, 2.81). An
      association was found for shared epitopes alleles with bronchiolitic AD (P =
      0.0040, OR = 2.06, 95% CI: 1.24, 3.41). DQB1*03:01 was associated with
      bronchiectatic AD (P = 0.0021, corrected P-value (Pc) = 0.0315, OR = 1.99, 95%
      CI: 1.30, 3.06), as well as with emphysema (P = 0.0007, Pc = 0.0104, OR = 2.43,
      95% CI: 1.49, 3.95). In combined analysis, a predisposing association of
      DQB1*03:01 (P = 1.94 *10(-5), Pc = 0.0003, OR = 2.16, 95% CI: 1.53, 3.06) and a
      negative association of DQB1*03:02 (P = 0.0008, Pc = 0.0117, OR = 0.33, 95% CI:
      0.17, 0.67) with bronchiectatic AD or emphysema were observed in RA. CONCLUSION:
      The present study identified an association of HLA-DQB1*03:01 with predisposition
      to, and DQB1*03:02 with resistance to, bronchiectatic AD or emphysema in RA.

PMID- 27048629
TI  - Electrospun PLLA nanofiber scaffolds for bladder smooth muscle reconstruction.
AB  - PURPOSE: Urinary bladder may encounter several pathologic conditions that could
      lead to loss of its function. Tissue engineering using electrospun PLLA scaffolds
      is a promising approach to reconstructing or replacing the problematic bladder.
      METHODS: PLLA nanofibrous scaffolds were prepared utilizing single-nozzle
      electrospinning. The morphology and distribution of fiber diameters were
      investigated by scanning electron microscopy (SEM). Human bladder smooth muscle
      cells (hBSMCs) were isolated from biopsies and characterized by
      immunocytochemistry (ICC). Then, the cells were seeded on the PLLA nanofibers and
      Alamar Blue assay proved the biocompatibility of prepared scaffolds. Cell
      attachment on the nanofibers and also cell morphology over fibrous scaffolds were
      observed by SEM. RESULTS: The results indicated that electrospun PLLA scaffold
      provides proper conditions for hBSMCs to interact and attach efficiently to the
      fibers. Alamar Blue assay showed the compatibility of the obtained electrospun
      scaffolds with hBSMCs. Also, it was observed that the cells could achieve highly
      elongated morphology and their native aligned direction besides each other on the
      random electrospun scaffolds and in the absence of supporting aligned nanofibers.
      CONCLUSION: Electrospun PLLA scaffold efficiently supports the hBSMCs growth and
      alignment and also has proper cell compatibility. This scaffold would be
      promising in urinary bladder tissue engineering.

PMID- 27048630
TI  - Time trends in educational inequalities in cancer mortality in Colombia, 1998
      2012.
AB  - OBJECTIVES: To evaluate trends in premature cancer mortality in Colombia by
      educational level in three periods: 1998-2002 with low healthcare insurance
      coverage, 2003-2007 with rapidly increasing coverage and finally 2008-2012 with
      almost universal coverage (2008-2012). SETTING: Colombian population-based,
      national secondary mortality data. PARTICIPANTS: We included all (n=188,091)
      cancer deaths occurring in the age group 20-64 years between 1998 and 2012,
      excluding only cases with low levels of quality of registration (n=2902, 1.5%).
      PRIMARY AND SECONDARY OUTCOME MEASURES: In this descriptive study, we linked
      mortality data of ages 20-64 years to census data to obtain age-standardised
      cancer mortality rates by educational level. Using Poisson regression, we
      modelled premature mortality by educational level estimating rate ratios (RR),
      relative index of inequality (RII) and the Slope Index of Inequality (SII).
      RESULTS: Relative measures showed increased risks of dying among the lower
      educated compared to the highest educated; this tendency was stronger in women
      (RRprimary 1.49; RRsecondary 1.22, both p<0.0001) than in men (RRprimary 1.35;
      RRsecondary 1.11, both p<0.0001). In absolute terms (SII), cancer caused a
      difference per 100 000 deaths between the highest and lowest educated of 20.5 in
      males and 28.5 in females. RII was significantly higher among women and the
      younger age categories. RII decreased between the first and second periods;
      afterwards (2008-2012), it increased significantly back to their previous levels.
      Among women, no significant increases or declines in cancer mortality over time
      were observed in recent periods in the lowest educated group, whereas strong
      recent declines were observed in those with secondary education or higher.
      CONCLUSIONS: Educational inequalities in cancer mortality in Colombia are
      increasing in absolute and relative terms, and are concentrated in young age
      categories. This trend was not curbed by increases in healthcare insurance
      coverage. Policymakers should focus on improving equal access to prevention,
      early detection, diagnostic and treatment facilities.

PMID- 27048631
TI  - New index of social deprivation during pregnancy: results from a national study
      in France.
AB  - OBJECTIVES: To identify precariousness markers in pregnant women that differ from
      the usual socioeconomic variables. METHODS: Data were obtained from the National
      Perinatal Survey, a representative sample of women giving birth in France in
      2010. From six indicators of social vulnerability, four were selected by multiple
      correspondence analysis. The first axis of this analysis was used, characterised
      by the following contributory variables: receiving RSA (Revenu de Solidarite
      Active) allowance; benefitting from the CMU (Couverture Maladie Universelle)
      system (French social security) or not being insured; not living in own
      accommodation; and not living with a partner. These four variables were summed to
      create a deprivation index. RESULTS: This index was strongly associated with
      social maternal characteristics and correctly identified women who were socially
      vulnerable. Furthermore, it was highly related to the psychosocial context,
      access to care, behaviours during pregnancy, and pregnancy outcomes. These
      associations remained significant after adjustment for social variables: compared
      with no deprivation (no factors), a high level of deprivation (>=3 factors) was
      associated with late prenatal care (OR 5.8, 95% CI 4.6 to 7.2) and small for
      gestational age (OR 1.5, 95% CI 1.1 to 1.9). CONCLUSIONS: This index of social
      deprivation was associated with health issues and behaviours during pregnancy,
      even after adjustment for social variables, revealing a dimension not measured by
      the usual variables. Moreover, it is simple to use and easily reproducible.

PMID- 27048632
TI  - Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective,
      observational study of patients treated with infliximab for ankylosing
      spondylitis.
AB  - OBJECTIVES: To describe the profile of patients with ankylosing spondylitis (AS)
      treated with infliximab in Canadian routine care and to assess the effectiveness
      and safety of infliximab in real world. SETTING: 46 primary care rheumatology
      practices across Canada. PARTICIPANTS: 303 biological-naive patients with AS or
      patients previously treated with a biological for <6 months and who were eligible
      for infliximab treatment as per routine care within the Biologic Treatment
      Registry Across Canada (BioTRAC). INTERVENTION: Not applicable (non
      interventional study). PRIMARY AND SECONDARY OUTCOMES: Effectiveness was assessed
      with changes in disease parameters (AS Disease Activity Score (ASDAS), Bath AS
      Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Health
      Assessment Questionnaire Disease Index (HAQ-DI), physician global assessment of
      disease activity (MDGA), patient global disease activity (PtGA), back pain, C
      reactive protein, erythrocyte sedimentation rate (ESR), morning stiffness).
      Safety was assessed with the incidence of adverse events (AEs). RESULTS: Of the
      303 patients included, 44.6% were enrolled in 2005-2007 and 55.4% in 2008-2013.
      Patients enrolled in 2005-2007 had significantly higher MDGA and ESR at baseline
      while all other disease parameters examined were numerically higher with the
      exception of PtGA. Treatment with infliximab significantly (p<0.001) improved all
      disease parameters over time in both groups. At 6 months, 56% and 31% of patients
      achieved clinically important (change>=1.1) and major (change>=2.0) improvement
      in ASDAS, respectively; at 48 months, these proportions increased to 75% and 50%,
      respectively. Among patients unemployed due to disability at baseline, 12.1%
      returned to work (mean Kaplan-Meier (KM)-based time=38.8 months). The estimated
      retention rate at 12 and 24 months was 78.3% and 60.1%, respectively. The profile
      and incidence of AEs were comparable to data previously reported for tumour
      necrosis factor-alpha inhibitors. CONCLUSIONS: Characteristics of patients with
      AS at infliximab initiation changed over time towards lower disease activity and
      shorter disease duration. Infliximab treatment significantly reduced disease
      activity independent of treatment initiation year, although patients enrolled in
      recent years achieved lower disease activity over 48 months. TRIAL REGISTRATION
      NUMBER: NCT00741793.

PMID- 27048633
TI  - Health and social consequences of an alcohol-related admission to critical care:
      a qualitative study.
AB  - OBJECTIVE: To examine the impact of critical care on future alcohol-related
      behaviour. Further, it aimed to explore patterns of recovery for patients with
      and without alcohol use disorders beyond the hospital environment. DESIGN: In
      depth, semistructured interviews with participants (patients) 3-7 months post
      intensive care discharge. SETTING: The setting for this study was a 20-bedded
      mixed intensive care unit (ICU), in a large teaching hospital in Scotland. On
      admission, patients were allocated to one of the three alcohol groups: low risk,
      harmful/hazardous and alcohol dependency. PARTICIPANTS: 21 participants who
      received mechanical ventilation for greater than 3 days were interviewed between
      March 2013 and June 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Four themes which impacted on recovery from ICU were identified in this patient
      group: psychological resilience, support for activities of daily living, social
      support and cohesion and the impact of alcohol use disorders on recovery.
      Participants also discussed the importance of personalised goal setting and
      appropriate and timely rehabilitation for alcohol-related behaviours during the
      critical care recovery period. CONCLUSIONS: There is a significant interplay
      between alcohol misuse and recovery from critical illness. This study has
      demonstrated that at present, there is a haphazard approach to rehabilitation for
      patients after ICU. A more targeted rehabilitation pathway for patients leaving
      critical care, with specific emphasis on alcohol misuse if appropriate, requires
      to be generated.

PMID- 27048634
TI  - Prenatal exposure to cannabis and maternal and child health outcomes: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effects of use of cannabis during pregnancy on maternal
      and fetal outcomes. DATA SOURCES: 7 electronic databases were searched from
      inception to 1 April 2014. Studies that investigated the effects of use of
      cannabis during pregnancy on maternal and fetal outcomes were included. STUDY
      SELECTION: Case-control studies, cross-sectional and cohort studies were
      included. DATA EXTRACTION AND SYNTHESIS: Data synthesis was undertaken via
      systematic review and meta-analysis of available evidence. All review stages were
      conducted independently by 2 reviewers. MAIN OUTCOMES AND MEASURES: Maternal,
      fetal and neonatal outcomes up to 6 weeks postpartum after exposure to cannabis.
      Meta-analyses were conducted on variables that had 3 or more studies that
      measured an outcome in a consistent manner. Outcomes for which meta-analyses were
      conducted included: anaemia, birth weight, low birth weight, neonatal length,
      placement in the neonatal intensive care unit, gestational age, head
      circumference and preterm birth. RESULTS: 24 studies were included in the review.
      Results of the meta-analysis demonstrated that women who used cannabis during
      pregnancy had an increase in the odds of anaemia (pooled OR (pOR)=1.36: 95% CI
      1.10 to 1.69) compared with women who did not use cannabis during pregnancy.
      Infants exposed to cannabis in utero had a decrease in birth weight (low birth
      weight pOR=1.77: 95% CI 1.04 to 3.01; pooled mean difference (pMD) for birth
      weight=109.42 g: 38.72 to 180.12) compared with infants whose mothers did not use
      cannabis during pregnancy. Infants exposed to cannabis in utero were also more
      likely to need placement in the neonatal intensive care unit compared with
      infants whose mothers did not use cannabis during pregnancy (pOR=2.02: 1.27 to
      3.21). CONCLUSIONS AND RELEVANCE: Use of cannabis during pregnancy may increase
      adverse outcomes for women and their neonates. As use of cannabis gains social
      acceptance, pregnant women and their medical providers could benefit from health
      education on potential adverse effects of use of cannabis during pregnancy.

PMID- 27048635
TI  - Cancer and non-cancer mortality among French uranium cycle workers: the TRACY
      cohort.
AB  - OBJECTIVES: The health effects of internal contamination by radionuclides, and
      notably by uranium, are poorly characterised. New cohorts of uranium workers are
      needed to better examine these effects. This paper analyses for the first time
      the mortality profile of the French cohort of uranium cycle workers. It considers
      mortality from cancer and non-cancer causes. METHODS: The cohort includes workers
      employed at least 6 months between 1958 and 2006 in French companies involved in
      the production of nuclear fuel. Vital status and causes of death were collected
      from French national registries. Workers were followed-up from 1 January 1968 to
      31 December 2008. Standardised mortality ratios (SMRs) were computed based on
      mortality rates for the French general population. RESULTS: The cohort includes
      12,649 workers (88% men). The average length of follow-up is 27 years and the
      mean age at the end of the study is 60 years. Large mortality deficits are
      observed for non-cancer causes of death such as non-cancer respiratory diseases
      (SMR=0.51 (0.41 to 0.63)) and circulatory diseases (SMR=0.68 (0.62 to 0.74)). A
      mortality deficit of lower magnitude is also observed for all cancers combined
      (SMR (95% CI): 0.76 (0.71 to 0.81)). Pleural mesothelioma is elevated (SMR=2.04
      (1.19 to 3.27)). CONCLUSIONS: A healthy worker effect is observed in this new
      cohort of workers involved in the uranium cycle. Collection of individual
      information on internal uranium exposure as well as other risk factors is
      underway, to allow for the investigation of uranium-related risks.

PMID- 27048636
TI  - Community social capital and tooth loss in Japanese older people: a longitudinal
      cohort study.
AB  - OBJECTIVE: To date, no study has prospectively examined the association between
      social capital (SC) in the community and oral health. The aim of this
      longitudinal cohort study was to examine the association between both community
      level and individual-level SC and tooth loss in older Japanese people. DESIGN:
      Prospective cohort study SETTING: We utilised data from the Japan Gerontological
      Evaluation Study (JAGES) performed in 2010 and 2013 and conducted in 525
      districts. PARTICIPANTS: The target population was restricted to non
      institutionalised people aged 65 years or older. Participants included 51 280
      people who responded to two surveys and who had teeth at baseline. PRIMARY
      OUTCOME MEASURE: The primary outcome measure was loss of remaining teeth,
      measured by the downward change of any category of remaining teeth, between
      baseline and follow-up. RESULTS: The mean age of the participants was 72.5 years
      (SD=5.4). During the study period, 8.2% (n=4180) lost one or more of their
      remaining teeth. Among three community-level SC variables obtained from factor
      analysis, an indicator of civic participation significantly reduced the risk of
      tooth loss (OR 0.93; 95% CI 0.88 to 0.99). The individual-level SC variables
      'hobby activity participation' and 'sports group participation' were also
      associated with a reduced risk of tooth loss (OR 0.88; 95% CI 0.81 to 0.95 and OR
      0.90; 95% CI 0.82 to 0.99, respectively). CONCLUSIONS: Living in a community with
      rich SC and individuals with good SC is associated with lower incidence of tooth
      loss among older Japanese people.

PMID- 27048637
TI  - Effect of vitamin D supplementation on inflammation: protocol for a systematic
      review.
AB  - INTRODUCTION: The extraskeletal role of vitamin D is being increasingly
      recognised. This has important clinical implications, as vitamin D deficiency has
      reached epidemic proportions worldwide. Vitamin D has proposed anti-inflammatory
      properties, yet the role of vitamin D supplementation in reducing inflammation
      remains largely unknown. The purpose of this review is to investigate the impact
      of vitamin D supplementation on inflammation, and to identify relevant knowledge
      gaps in the field. METHODS AND ANALYSIS: Medline, CINAHL, EMBASE and All EBM will
      be systematically searched for randomised controlled trials (RCTs) and systematic
      reviews of RCTs, comparing vitamin D supplementation with placebo, usual care or
      other pharmacological or non-pharmacological interventions. One reviewer will
      assess articles for eligibility according to prespecified selection criteria,
      after which 2 independent reviewers will perform data extraction and quality
      appraisal. Meta-analyses will be conducted where appropriate. ETHICS AND
      DISSEMINATION: Formal ethical approval is not required as no primary data is
      collected. This systematic review will identify potential clinical implications
      of vitamin D deficiency and supplementation, and will be disseminated through a
      peer-reviewed publication and at conference meetings, to inform future research
      on the efficacy of vitamin D supplementation for inflammation and inflammatory
      diseases. PROSPERO REGISTRATION NUMBER: CRD42016037104.

PMID- 27048638
TI  - Establishing the Aus-ROC Australian and New Zealand out-of-hospital cardiac
      arrest Epistry.
AB  - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a global health problem
      with low survival. Regional variation in survival has heightened interest in
      combining cardiac arrest registries to understand and improve OHCA outcomes.
      While individual OHCA registries exist in Australian and New Zealand ambulance
      services, until recently these registries have not been combined. The aim of this
      protocol paper is to describe the rationale and methods of the Australian
      Resuscitation Outcomes Consortium (Aus-ROC) OHCA epidemiological registry
      (Epistry). METHODS AND ANALYSIS: The Aus-ROC Epistry is designed as a population
      based cohort study. Data collection started in 2014. Six ambulance services in
      Australia (Ambulance Victoria, SA Ambulance Service, St John Ambulance Western
      Australia and Queensland Ambulance Service) and New Zealand (St John New Zealand
      and Wellington Free Ambulance) currently contribute data. All OHCA attended by
      ambulance, regardless of aetiology or patient age, are included in the Epistry.
      The catchment population is approximately 19.3 million persons, representing 63%
      of the Australian population and 100% of the New Zealand population. Data are
      collected using Utstein-style definitions. Information incorporated into the
      Epistry includes demographics, arrest features, ambulance response times,
      treatment and patient outcomes. The primary outcome is 'survival to hospital
      discharge', with 'return of spontaneous circulation' as a key secondary outcome.
      ETHICS AND DISSEMINATION: Ethics approval was independently sought by each of the
      contributing registries. Overarching ethics for the Epistry was provided by
      Monash University HREC (Approval No. CF12/3938-2012001888). A population-based
      OHCA registry capturing the majority of Australia and New Zealand will allow risk
      adjusted outcomes to be determined, to enable benchmarking across ambulance
      providers, facilitate the identification of system-wide strategies associated
      with survival from OHCA, and allow monitoring of temporal trends in process and
      outcomes to improve patient care. Findings will be shared with participating
      ambulance services and the academic community.

PMID- 27048639
TI  - Development of an HPLC Method for the Determination of Ceftolozane/Tazobactam in
      Biological and Aqueous Matrixes.
AB  - Herein, we report the development and validation of an HPLC method to analyze
      ceftolozane and tazobactam simultaneously in human plasma, human serum, swine
      serum and saline matrixes. A reversed-phase column was used with a UV detector
      set at 260 nm and switched to 218 nm. The mobile phase consisted of methanol and
      sodium phosphate buffer at a flow rate of 1.1 mL/min. Cefepime was used as the
      internal standard. The standard curves were linear over a range of 0.4-50 MUg/mL.
      This methodology represents a simple, reproducible approach to the determination
      of drug concentrations with sufficient accuracy and precision for pharmacokinetic
      studies undertaken with this recently FDA-approved antimicrobial therapy. 

PMID- 27048640
TI  - Combination with Chemometrics and Quantification for Quality Evaluation and
      Variety Identification of Flos Chimonanthi Praecocis by HPLC.
AB  - Flos Chimonanthi Praecocis (FCP) is one of the popular traditional Chinese
      medicines, which have been widely used in China. Inconspicuous appearance
      differences are disadvantageous for identification, and it is difficult to
      evaluate the quality of FCP using the current methods. In this article, a simple
      method that combined chemometrics and quantitative analysis was established. The
      samples were obtained from three typical varieties for fingerprint analysis by
      high-performance liquid chromatography. Contents of rutin and quercetin were
      determined, and then a common pattern with 16 characteristic peaks was applied
      for principal component analysis, similarity analysis, and the hierarchical
      cluster analysis heatmap (HCA heatmap) to characterize the similarity and
      differences among samples for identification. Furthermore, seven characteristics
      peaks with higher loading values were selected for chemometrics analysis after
      dimensionality reduction to reduce analytical difficulty, and the new common
      pattern showed the similar identification effects. Overall, combination with
      chemometrics and quantitative analysis would provide a useful and simple method
      for quality control of FCP in the future. 

PMID- 27048641
TI  - Qualitative and Quantitative Assessments of Aconiti Lateralis Radix Praeparata
      Using High-Performance Liquid Chromatography Coupled with Diode Array Detection
      and Hybrid Ion Trap-Time-of-Flight Mass Spectrometry.
AB  - Dual roles have been widely disclosed for Aconiti Lateralis Radix Praeparata
      (Chinese name: Fuzi) by acting as an effective herbal medicine accompanied with
      high toxicity risk and narrow therapeutic range. Aconite alkaloids, also known as
      diterpenoid alkaloids (DAs), have been proved to be primary therapeutic as well
      as toxic material basis of Fuzi. In the present study, we aim to characterize
      qualitative profile along with quantitative features of DAs in Fuzi, which could
      benefit the quality control of Fuzi as well as its safe medication in clinic.
      Chromatographic fingerprinting was achieved using 12 batches of crude materials
      collected from different habitats (similarities >0.9) by hyphenating liquid
      chromatography (LC) with diode array detection. Simultaneous determination of six
      primary DAs, namely benzoylmesaconine, benzoylaconine, benzoylhypaconine,
      mesaconine, aconitine and hypaconitine, was also carried out. The developed
      method was systematically validated and successfully applied for quantitative
      characterization. Significant variations were observed regarding the contents of
      those six analytes among different raw materials. A total of 99 DAs were detected
      and characterized, including 9 unambiguous identities and 77 putative
      assignments, as well as 13 unknown compounds, from the representative extract by
      LC coupled with hybrid ion trap-time-of-flight mass spectrometry. The findings
      obtained herein could favor in-depth understanding of the chemical composition of
      DAs and the quality control of Fuzi. 

PMID- 27048642
TI  - Stability-Indicating HPLC-UV Method for Vitamin D3 Determination in Solutions,
      Nutritional Supplements and Pharmaceuticals.
AB  - A simple and fast high-performance liquid chromatography method with UV detection
      for determination of vitamin D3 in stability studies as well as in solutions,
      nutritional supplements and pharmaceuticals was developed. Successful separation
      of vitamin D3 from its degradation products was achieved on a Gemini C18 100 *
      3.0 mm column using a mixture of acetonitrile and water (99:1, v/v) as a mobile
      phase. The method was successfully validated according to the ICH guidelines. The
      described reversed-phase HPLC method is favorable compared with other published
      HPLC-UV methods because of its stability-indicating nature, short run time (3.3
      min) and wide analytical range with outstanding linearity, accuracy and
      precision. The method was further applied for quantification of vitamin D3 in
      selected liquid and solid nutritional supplements and prescription medicines,
      confirming its suitability for routine analysis. Degradation products, formed
      under stress conditions (hydrolysis, oxidation, photolysis and thermal
      degradation), were additionally elucidated by suitable equipment (LC-DAD-MS) to
      confirm the stability-indicating nature of the developed method. 

PMID- 27048643
TI  - HPLC Determination of Enantiomeric Purity of Letermovir Based on CHIRALPAK AD.
AB  - A precise and sensitive LC method was developed and further validated for the
      determination of enantiomeric purity of {(4S)-8-Fluoro-2-[4-(3-methoxyphenyl)-1
      piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydro-4-quinazolinyl}
      acetic acid (Letermovir). Baseline separation with a resolution >2.8 was
      accomplished within 10 min using a CHIRALPAK AD (250 mm * 4.6 mm; particle size 5
      MUm) column, withn-hexane/2-propanol (80:20v/v) as mobile phase at a flow rate of
      1 mL min-1 The eluted analytes were monitored by UV detection at 260 nm. The
      effects of mobile phase composition and temperature on enantiomeric selectivity
      as well as resolution of enantiomers were thoroughly investigated. The
      calibration curves were plotted within the concentration range between 0.003 and
      1 mg mL-1(n= 14), and the recoveries between 98.24 and 101.43% were obtained,
      with relative standard deviation <1.29%. The limit of detection (LOD) and limit
      of quantitation (LOQ) for Letermovir were 0.96 and 3.15 MUg mL-1; those for its
      enantiomer were 1.01 and 3.39 MUg mL-1, respectively. The developed method was
      demonstrated to be accurate, robust and sensitive for the determination of
      enantiomeric purity of Letermovir, especially for the analysis of bulk samples.

PMID- 27048644
TI  - Development and Validation of an LC-MS-MS Method for the Simultaneous
      Determination of Simvastatin, Simvastatin Acid and Ezetimibe in Human Plasma and
      Its Application to Pharmacokinetic Study in the Indian Population.
AB  - A simple, selective, sensitive and high-throughput liquid chromatography-tandem
      mass spectrometry (LC-MS-MS) method has been developed and validated for the
      simultaneous quantification of simvastatin (SS), simvastatin acid (SSA, active
      metabolite of SS) and ezetimibe (EZM) in K2 EDTA containing human plasma, using
      simvastatin D6, simvastatin acid D3 and ezetimibe D4 as internal standards
      (ISTDs), respectively. A volume of plasma sample of only 400 uL was processed by
      the solid phase extraction technique; then 20 uL of processed sample was run on a
      Phenomenex, Kinetix XB C18, 150 * 4.6 mm, 5 um column using an isocratic mobile
      phase consisting of 10 mM ammonium formate buffer (pH 4.0 +/- 0.3): acetonitrile
      (27 : 73, v/v) with a run time of 6.3 min. The precursor and product ions of SSA,
      EZM and their ISTDs were monitored on a triple quadrupole instrument operated in
      the negative ionization mode, and SS was monitored in the positive mode. The
      method was validated over a concentration range of 0.2-80 ng/mL for SS, 0.1-60
      ng/mL for SSA and 0.05-15 ng/mL for EZM. The method has been successfully applied
      in clinical pharmacokinetic study in the Indian population. The Cmax, AUC0-inf
      and Tmax values obtained in our study were 10.61 +/- 5.287, 77.58 +/- 29.367 and
      1.62 +/- 0.436 for EZM; 69.74 +/- 45.274, 190.71 +/- 107.271 and 1.74 +/- 0.480
      for SS; and 25.36 +/- 23.576, 139.24 +/- 131.653 and 3.95 +/- 0.671 for SSA,
      respectively. 

PMID- 27048645
TI  - A Simple and Rapid UPLC Method for the Determination of Rosavin in Rat Plasma and
      Its Application to a Pharmacokinetic Study.
AB  - Rosavin is a bioactive antidepressant component isolated from Rhodiola rosea L.
      In this work, an ultra-performance liquid chromatography (UPLC) method was
      established for the determination of rosavin in rat plasma. The chromatographic
      separation was achieved on a HSS T3 column (100 mm * 2.1 mm, 1.8 MUm) with a
      gradient mobile phase consisting of acetonitrile and water (0.1% formic acid).
      Plasma samples were processed with one-step protein precipitation. Rutin was
      chosen as internal standard and the detection wavelength was 249 nm. The
      pharmacokinetic parameters were analyzed using the drug and statistics software.
      The results showed that the established method has an excellent linearity in the
      range of 10-1,000 ng/mL (R(2) = 0.992) with a lower limit of quantification (10
      ng/mL). The intra- and interday precision (relative standard deviation) were from
      2.0 to 10.6% and the extraction recovery was 92.4-95.1%. The simple and rapid
      UPLC method was successfully applied to the pharmacokinetic and bioavailability
      study of rosavin in rats. 

PMID- 27048646
TI  - Extraction of Citrus paradisi Volatile Components by Headspace Single-Drop
      Microextraction and Statistical Modeling.
AB  - In present study, headspace single-drop microextraction (HS-SDME) was applied for
      the extraction and preconcentration of the volatile components of the plant
      sample into a microdrop surface. The extraction occurred by suspending a
      microliter drop of the solvent from the tip of a microsyringe to the headspace of
      a ripe fruit sample (grapefruit Citrus paradisi) in a sealed vial for a preset
      extraction time. Then the microdrop was retracted back into the microsyringe and
      injected directly into a gas chromatography injection port. The chemical
      composition of the SDME extracts was confirmed according to their mass spectra,
      and quantitative analysis was performed by gas chromatography-flame ionization
      detector (GC-FID). Response surface methodology along with Box-Behnken design was
      applied to optimize the extraction condition of four components, d-limonene, beta
      myrcene, alpha-pinene and beta-pinene, from the peel of grapefruit. Parameters
      considered for SDME include the kind of the extracting solvent, size of drop,
      extraction temperature and extraction time. The optimized condition was microdrop
      volume of 1 uL, extraction time of 2 min and sample temperature of 50 degrees C. 

PMID- 27048647
TI  - Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without
      susceptibility to periodic paralysis.
AB  - Over 60 mutations of SCN4A encoding the NaV1.4 sodium channel of skeletal muscle
      have been identified in patients with myotonia, periodic paralysis, myasthenia,
      or congenital myopathy. Most mutations are missense with gain-of-function defects
      that cause susceptibility to myotonia or periodic paralysis. Loss-of-function
      from enhanced inactivation or null alleles is rare and has been associated with
      myasthenia and congenital myopathy, while a mix of loss and gain of function
      changes has an uncertain relation to hypokalaemic periodic paralysis. To better
      define the functional consequences for a loss-of-function, we generated NaV1.4
      null mice by deletion of exon 12. Heterozygous null mice have latent myasthenia
      and a right shift of the force-stimulus relation, without evidence of periodic
      paralysis. Sodium current density was half that of wild-type muscle and no
      compensation by retained expression of the foetal NaV1.5 isoform was detected.
      Mice null for NaV1.4 did not survive beyond the second postnatal day. This mouse
      model shows remarkable preservation of muscle function and viability for
      haploinsufficiency of NaV1.4, as has been reported in humans, with a propensity
      for pseudo-myasthenia caused by a marginal Na(+) current density to support
      sustained high-frequency action potentials in muscle.

PMID- 27048648
TI  - Rapamycin reverses the senescent phenotype and improves immunoregulation of
      mesenchymal stem cells from MRL/lpr mice and systemic lupus erythematosus
      patients through inhibition of the mTOR signaling pathway.
AB  - We have shown that bone marrow (BM)-derived mesenchymal stem cells (BM-MSCs) from
      SLE patients exhibit senescent behavior and are involved in the pathogenesis of
      SLE. The aim of this study was to investigate the effects of rapamycin (RAPA) on
      the senescences and immunoregulatory ability of MSCs of MRL/lpr mice and SLE
      patients and the underlying mechanisms. Cell morphology, senescence associated
      beta-galactosidase (SA-beta-gal) staining, F-actin staining were used to detect
      the senescence of cells. BM-MSCs and purified CD4+ T cells were co-cultured
      indirectly. Flow cytometry was used to inspect the proportion of regulatory T
      (Treg) /T helper type 17 (Th17). We used small interfering RNA (siRNA) to
      interfere the expression of mTOR, and detect the effects by RT-PCR, WB and
      immunofluorescence. Finally, 1x106 of SLE BM-MSCs treated with RAPA were
      transplanted to cure the 8 MRL/lpr mice aged 16 weeks for 12 weeks. We
      demonstrated that RAPA alleviated the clinical symptoms of lupus nephritis and
      prolonged survival in MRL/lpr mice. RAPA reversed the senescent phenotype and
      improved immunoregulation of MSCs from MRL/lpr mice and SLE patients through
      inhibition of the mTOR signaling pathway. Marked therapeutic effects were
      observed in MRL/lpr mice following transplantation of BM-MSCs from SLE patients
      pretreated with RAPA.

PMID- 27048649
TI  - Reduction of Flavodoxin by Electron Bifurcation and Sodium Ion-dependent
      Reoxidation by NAD+ Catalyzed by Ferredoxin-NAD+ Reductase (Rnf).
AB  - Electron-transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) from
      Acidaminococcus fermentans catalyze the endergonic reduction of ferredoxin by
      NADH, which is also driven by the concomitant reduction of crotonyl-CoA by NADH,
      a process called electron bifurcation. Here we show that recombinant flavodoxin
      from A. fermentans produced in Escherichia coli can replace ferredoxin with
      almost equal efficiency. After complete reduction of the yellow quinone to the
      blue semiquinone, a second 1.4 times faster electron transfer affords the
      colorless hydroquinone. Mediated by a hydrogenase, protons reoxidize the fully
      reduced flavodoxin or ferredoxin to the semi-reduced species. In this hydrogen
      generating system, both electron carriers act catalytically with apparent Km =
      0.26 MUm ferredoxin or 0.42 MUm flavodoxin. Membrane preparations of A.
      fermentans contain a highly active ferredoxin/flavodoxin-NAD(+) reductase (Rnf)
      that catalyzes the irreversible reduction of flavodoxin by NADH to the blue
      semiquinone. Using flavodoxin hydroquinone or reduced ferredoxin obtained by
      electron bifurcation, Rnf can be measured in the forward direction, whereby one
      NADH is recycled, resulting in the simple equation: crotonyl-CoA + NADH + H(+) =
      butyryl-CoA + NAD(+) with Km = 1.4 MUm ferredoxin or 2.0 MUm flavodoxin. This
      reaction requires Na(+) (Km = 0.12 mm) or Li(+) (Km = 0.25 mm) for activity,
      indicating that Rnf acts as a Na(+) pump. The redox potential of the
      quinone/semiquinone couple of flavodoxin (Fld) is much higher than that of the
      semiquinone/hydroquinone couple. With free riboflavin, the opposite is the case.
      Based on this behavior, we refine our previous mechanism of electron bifurcation.

PMID- 27048650
TI  - Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo
      Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ).
AB  - Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated
      protein (YAP) are critical transcriptional co-activators downstream of the Hippo
      pathway involved in the regulation of organ size, tissue regeneration,
      proliferation, and apoptosis. Recent studies suggested common and distinct
      functions of TAZ and YAP and their diverse impact under several pathological
      conditions. Here we report differential regulation of TAZ and YAP in response to
      oxidative stress. H2O2 exposure leads to increased stability and activation of
      TAZ but not of YAP. H2O2 induces reversible S-glutathionylation at conserved
      cysteine residues within TAZ. We further demonstrate that TAZ S-glutathionylation
      is critical for reactive oxygen species (ROS)-mediated, TAZ-dependent TEA domain
      transcription factor (TEAD) trans-activation. Lysophosphatidic acid, a
      physiological activator of YAP and TAZ, induces ROS elevation and, subsequently,
      TAZ S-glutathionylation, which promotes TAZ-mediated target gene expression. TAZ
      expression is essential for renal homeostasis in mice, and we identify basal TAZ
      S-glutathionylation in murine kidney lysates, which is elevated during
      ischemia/reperfusion injury in vivo This induced nuclear localization of TAZ and
      increased expression of connective tissue growth factor. These results describe a
      novel mechanism by which ROS sustains total cellular levels of TAZ. This
      preferential regulation suggests TAZ to be a redox sensor of the Hippo pathway.

PMID- 27048651
TI  - The Ubiquitin Ligases c-Cbl and Cbl-b Negatively Regulate Platelet-derived Growth
      Factor (PDGF) BB-induced Chemotaxis by Affecting PDGF Receptor beta (PDGFRbeta)
      Internalization and Signaling.
AB  - Protein ubiquitination controls protein stability and subcellular localization of
      tyrosine kinase receptors, hence affecting signaling both quantitatively and
      qualitatively. In this report, we demonstrate that, after ligand stimulation, the
      PDGF beta receptor (PDGFRbeta) becomes ubiquitinated in a manner requiring both
      the c-Cbl and Cbl-b ubiquitin ligases. Simultaneous depletion of c-Cbl and Cbl-b
      resulted in reduced ligand-induced PDGFRbeta clearance from the cell surface
      because of reduced endocytosis of the receptor. Cbl-b formed a complex with c
      Cbl, as well as with the PDGFRbeta, in response to PDGF-BB stimulation. We were
      unable to find a direct interaction between the receptor and c-Cbl, raising the
      possibility that Cbl-b is necessary for c-Cbl to interact with PDGFRbeta.
      Phosphorylated Tyr-1021 in PDGFRbeta was the primary interaction site for Cbl-b,
      with some contribution from Tyr-1009. Depletion of c-Cbl and Cbl-b led to an
      increased ligand-induced tyrosine phosphorylation of the receptor. Several
      tyrosine residues with elevated phosphorylation (i.e. Tyr-579, Tyr-581, Tyr-1009,
      and Tyr-1021) have previously been shown to interact with Src kinases and
      PLCgamma. Indeed, in cells depleted of c-Cbl and Cbl-b, both Src and PLCgamma
      phosphorylation were enhanced, whereas activation of other pathways, such as
      Erk1/2 MAP kinase and Akt, were not affected. In addition, Stat3 phosphorylation,
      which has been connected to Src activity, was also elevated in cells lacking c
      Cbl and Cbl-b. Functionally, we found that cells depleted of c-Cbl and Cbl-b were
      more prone to migrate toward PDGF-BB, whereas no reproducible effect on cell
      proliferation could be observed. In conclusion, internalization as well as
      signaling via PDGFRbeta are controlled by ubiquitination.

PMID- 27048652
TI  - Compartment-specific Control of Reactive Oxygen Species Scavenging by Antioxidant
      Pathway Enzymes.
AB  - Oxidative stress arises from an imbalance in the production and scavenging rates
      of reactive oxygen species (ROS) and is a key factor in the pathophysiology of
      cardiovascular disease and aging. The presence of parallel pathways and multiple
      intracellular compartments, each having its own ROS sources and antioxidant
      enzymes, complicates the determination of the most important regulatory nodes of
      the redox network. Here we quantified ROS dynamics within specific intracellular
      compartments in the cytosol and mitochondria and determined which scavenging
      enzymes exert the most control over antioxidant fluxes in H9c2 cardiac myoblasts.
      We used novel targeted viral gene transfer vectors expressing redox-sensitive GFP
      fused to sensor domains to measure H2O2 or oxidized glutathione. Using genetic
      manipulation in heart-derived H9c2 cells, we explored the contribution of
      specific antioxidant enzymes to ROS scavenging and glutathione redox potential
      within each intracellular compartment. Our findings reveal that antioxidant flux
      is strongly dependent on mitochondrial substrate catabolism, with availability of
      NADPH as a major rate-controlling step. Moreover, ROS scavenging by mitochondria
      significantly contributes to cytoplasmic ROS handling. The findings provide
      fundamental information about the control of ROS scavenging by the redox network
      and suggest novel interventions for circumventing oxidative stress in cardiac
      cells. 

PMID- 27048653
TI  - A New STAT3-binding Partner, ARL3, Enhances the Phosphorylation and Nuclear
      Accumulation of STAT3.
AB  - Signal transducer and activator of transcription 3 (STAT3) is involved in cell
      proliferation, differentiation, and cell survival during immune responses,
      hematopoiesis, neurogenesis, and other biological processes. STAT3 activity is
      regulated by a variety of mechanisms, including phosphorylation and nuclear
      translocation. To clarify the molecular mechanisms underlying the regulation of
      STAT3 activity, we performed yeast two-hybrid screening. We identified ARL3 (ADP
      ribosylation factor-like 3) as a novel STAT3-binding partner. ARL3 recognizes the
      DNA-binding domain as well as the C-terminal region of STAT3 in vivo, and their
      binding was the strongest when both proteins were activated. Importantly, small
      interfering RNA-mediated reduction of endogenous ARL3 expression decreased IL-6
      induced tyrosine phosphorylation, nuclear accumulation, and transcriptional
      activity of STAT3. These results indicate that ARL3 interacts with STAT3 and
      regulates the transcriptional activation of STAT3 by influencing its nuclear
      accumulation of STAT3. 

PMID- 27048654
TI  - Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription
      in Human Thymic Epithelial Cells.
AB  - INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune
      regulator) have been associated with the modulation of insulin gene expression in
      thymus, which is essential to induce either insulin tolerance or the development
      of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each
      functional domain of AIRE is critical for the activation of INS-VNTR in human
      thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two
      chimeric AIRE constructs were generated. A luciferase reporter assay and a
      pulldown assay using biotinylated INS-class I VNTR probe were performed to
      examine the transactivation and binding activities of WT, mutant, and chimeric
      AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT
      or mutant AIRE cellular localization. We found that all of the AIRE mutations
      resulted in loss of transcriptional activation of INS-VNTR except mutant P252L.
      Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed
      five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that
      functioned in a dominant negative fashion. The LXXLL-3 motif is identified for
      the first time to be essential for DNA binding to INS-VNTR, whereas the intact
      PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful
      transcriptional activation. AIRE nuclear localization in the human thymic
      epithelial cell line was disrupted by mutations in the homogenously staining
      region domain and the R257X mutation in the PHD1 domain. This study supports the
      notion that AIRE mutation could specifically affect human insulin gene expression
      in thymic epithelial cells through INS-VNTR and subsequently induce either
      insulin tolerance or autoimmunity. 

PMID- 27048657
TI  - Into Action: Improving Access to Optimum Care for all Primary Immunodeficiency
      Patients.

PMID- 27048655
TI  - Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth
      Factor Expression from Keratinocytes and Endothelial Cells.
AB  - A critical function for skin is that when damaged it must simultaneously identify
      the nature of the injury, repair barrier function, and limit the intrusion of
      pathogenic organisms. These needs are carried out through the detection of damage
      associated molecular patterns (DAMPs) and a response that includes secretion of
      cytokines, chemokines, growth factors, and antimicrobial peptides (AMPs). In this
      study, we analyzed how non-coding double-stranded RNA (dsRNAs) act as a DAMP in
      the skin and how the human cathelicidin AMP LL-37 might influence growth factor
      production in response to this DAMP. dsRNA alone significantly increased the
      expression of multiple growth factors in keratinocytes, endothelial cells, and
      fibroblasts. Furthermore, RNA sequencing transcriptome analysis found that
      multiple growth factors increase when cells are exposed to both LL-37 and dsRNA,
      a condition that mimics normal wounding. Quantitative PCR and/or ELISA validated
      that growth factors expressed by keratinocytes in these conditions included, but
      were not limited to, basic fibroblast growth factor (FGF2), heparin-binding EGF
      like growth factor (HBEGF), vascular endothelial growth factor C (VEGFC),
      betacellulin (BTC), EGF, epiregulin (EREG), and other members of the transforming
      growth factor beta superfamily. These results identify a novel role for DAMPs and
      AMPs in the stimulation of repair and highlight the complex interactions involved
      in the wound environment.

PMID- 27048656
TI  - Copa Syndrome: a Novel Autosomal Dominant Immune Dysregulatory Disease.
AB  - Inherently defective immunity typically results in either ineffective host
      defense, immune regulation, or both. As a category of primary immunodeficiency
      diseases, those that impair immune regulation can lead to autoimmunity and/or
      autoinflammation. In this review we focus on one of the most recently discovered
      primary immunodeficiencies that leads to immune dysregulation: "Copa syndrome".
      Copa syndrome is named for the gene mutated in the disease, which encodes the
      alpha subunit of the coatomer complex-I that, in aggregate, is devoted to
      transiting molecular cargo from the Golgi complex to the endoplasmic reticulum
      (ER). Copa syndrome is autosomal dominant with variable expressivity and results
      from mutations affecting a narrow amino acid stretch in the COPA gene-encoding
      COPalpha protein. Patients with these mutations typically develop arthritis and
      interstitial lung disease with pulmonary hemorrhage representing a striking
      feature. Immunologically Copa syndrome is associated with autoantibody
      development, increased Th17 cells and pro-inflammatory cytokine expression
      including IL-1beta and IL-6. Insights have also been gained into the underlying
      mechanism of Copa syndrome, which include excessive ER stress owing to the
      impaired return of proteins from the Golgi, and presumably resulting aberrant
      cellular autophagy. As such it represents a novel cellular disorder of
      intracellular trafficking associated with a specific clinical presentation and
      phenotype.

PMID- 27048658
TI  - Per Oral Endoscopic Myotomy in Children with Achalasia Cardia.
AB  - Background/Aims: Achalasia cardia (AC) is a motility disorder, characterized by
      impaired lower esophageal sphincter relaxation and absence of esophageal
      peristalsis. AC is rare in children with unclear optimum management strategies.
      Per oral endoscopic myotomy (POEM) is a novel technique for management of
      achalasia with encouraging results in adult patients. The efficacy and safety of
      POEM is not known for pediatric AC. The aim of our study was to evaluate the
      safety and efficacy of POEM in children with achalasia cardia. Methods: The data
      of all children (< 18 years) who underwent POEM at our center was retrospectively
      analysed. Symptoms were analysed using a validated score (Eckardt score) at
      regular predefined intervals. Objective parameters including high-resolution
      manometry, timed barium swallow and esophagogastroduodenoscopy were assessed
      before the procedure and at 1-year follow-up. Clinical success was defined as an
      Eckardt score <= 3. Results: A total of 15 children underwent POEM during the
      specified period. Ten out of 15 (10/15) completed 1-year follow-up. Median
      operative time was 100 (38-240) minutes. Mean pre and post procedure LES pressure
      were 36.64 +/- 11.08 mmHg and 15.65 +/- 5.73 mmHg, respectively (P = 0.001). Mean
      Eckardt score before and after the POEM was 7.32 +/- 1.42 and 1.74 +/- 0.67,
      respectively (P = 0.001). Mean percentage improvement in barium emptying at 5
      minutes was 63.70 +/- 4.46%. All children had complete resolution of symptoms at
      1 year. Median weight gain of children at 1 year was 0.65 kg (range, 0.0-4.6).
      Conclusions: POEM is safe and effective for children and adolescents with
      achalasia. Future trials with larger sample size are warranted to establish its
      efficacy in pediatric AC.

PMID- 27048659
TI  - BI 1002494, a Novel Potent and Selective Oral Spleen Tyrosine Kinase Inhibitor,
      Displays Differential Potency in Human Basophils and B Cells.
AB  - BI 1002494 [(R)-4-{(R)-1-[7-(3,4,5-trimethoxy-phenyl)-[1,6]napthyridin-5-yloxy]
      ethyl}pyrrolidin-2-one] is a novel, potent, and selective spleen tyrosine kinase
      (SYK) inhibitor with sustained plasma exposure after oral administration in rats,
      which qualifies this molecule as a good in vitro and in vivo tool compound. BI
      1002494 exhibits higher potency in inhibiting high-affinity IgE receptor-mediated
      mast cell and basophil degranulation (IC50 = 115 nM) compared with B-cell
      receptor-mediated activation of B cells (IC50 = 810 nM). This may be explained by
      lower kinase potency when the physiologic ligand B-cell linker was used,
      suggesting that SYK inhibitors may exhibit differential potency depending on the
      cell type and the respective signal transduction ligand. A 3-fold decrease in
      potency was observed in rat basophils (IC50 = 323 nM) compared with human
      basophils, but a similar species potency shift was not observed in B cells. The
      lower potency in rat basophils was confirmed in both ex vivo inhibition of
      bronchoconstriction in precision-cut rat lung slices and in reversal of
      anaphylaxis-driven airway resistance in rats. The different cellular potencies
      translated into different in vivo efficacy; full efficacy in a rat ovalbumin
      model (that contains an element of mast cell dependence) was achieved with a
      trough plasma concentration of 340 nM, whereas full efficacy in a rat collagen
      induced arthritis model (that contains an element of B-cell dependence) was
      achieved with a trough plasma concentration of 1400 nM. Taken together, these
      data provide a platform from which different estimates of human efficacious
      exposures can be made according to the relevant cell type for the indication
      intended to be treated.

PMID- 27048660
TI  - beta-Lapachone Induces NAD(P)H:Quinone Oxidoreductase-1- and Oxidative Stress
      Dependent Heat Shock Protein 90 Cleavage and Inhibits Tumor Growth and
      Angiogenesis.
AB  - beta-Lapachone [beta-lap; 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6
      dione] is a novel anticancer drug currently under investigation in phase I/II
      clinical trials. However, the mechanism underlying its clinical efficacy remains
      unclear. In this study, we found that beta-lap provoked the cleavage of heat
      shock protein 90 (Hsp90) in NAD(P)H: quinone oxidoreductase-1 (NQO1)-expressing
      lung and prostate cancer cells as well as in primary human umbilical vein
      endothelial cells (HUVECs). These actions of beta-lap were different from that of
      the conventional Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. As a
      consequence of Hsp90 cleavage, Hsp90-associated oncoproteins, such as receptor
      interacting protein, Raf-1, AKT, and CDK4, were degraded in treated cancer cells,
      and key receptor tyrosine kinases such as vascular endothelial cell growth factor
      receptor-2 and Her-2 were degraded in treated HUVECs through a proteasomal
      system. Further results revealed that specific inhibitors of NQO1 and reactive
      oxygen species could dramatically reduce beta-lap-mediated Hsp90 cleavage. In
      addition to its cytotoxicity, beta-lap effectively inhibited angiogenesis by
      suppressing tube formation and the invasion of HUVECs in vitro, rat aortic
      microvascular sprouts ex vivo, and mouse corneal neovascularization in vivo.
      Furthermore, beta-lap markedly suppressed the growth and angiogenesis of human
      lung cancer xenografts in nude mice and decreased the levels of receptor
      interacting protein, AKT, CDK4, and CD31 in the solid tumors. Unlike other NQO1
      dependent cytotoxic quinones, such as streptonigrin, menadione, mitomycin, and 17
      allylamino-17-demethoxygeldanamycin, beta-lap was the only agent that could cause
      Hsp90 cleavage. Taken together, our results suggest a crucial mechanism
      underlying the antitumor efficacy of beta-lap.

PMID- 27048661
TI  - Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin
      (Serelaxin).
AB  - Cigarette smoke (CS) is the major etiologic factor of chronic obstructive
      pulmonary disease (COPD), which is characterized by airway remodeling, lung
      inflammation and fibrosis, emphysema, and respiratory failure. The current
      therapies can improve COPD management but cannot arrest its progression and
      reduce mortality. Hence, there is a major interest in identifying molecules
      susceptible of development into new drugs to prevent or reduce CS-induced lung
      injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate
      because of its anti-inflammatory and antifibrotic properties highlighted in lung
      disease models. Here, we used a guinea pig model of CS-induced lung inflammation,
      and remodeling reproducing some of the hallmarks of COPD. Animals exposed
      chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by
      osmotic pumps (1 or 10 MUg/day) or aerosol (10 MUg/ml/day) during CS treatment.
      Controls were nonsmoking animals. RLX maintained airway compliance to a control
      like pattern, likely because of its capability to counteract lung inflammation
      and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX
      reduced the inflammatory recruitment of leukocytes, accompanied by a significant
      reduction of the release of proinflammatory cytokines (tumor necrosis factor
      alpha and interleukin-1beta). Moreover, RLX was able to counteract the adverse
      bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell
      hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by
      aerosol has shown a comparable efficacy to systemic administration in reducing CS
      induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule
      to counteract CS-induced inflammatory lung diseases.

PMID- 27048662
TI  - Salivary Stone Pneumatic Lithotripsy in a Live Porcine Model.
AB  - The purpose of this study is to evaluate the efficacy of endoscopic fragmentation
      and removal of artificial calculi in a live porcine model employing
      intracorporeal pneumatic lithotripsy. In this experimental study, 7 submandibular
      ducts were accessed and artificial calculi placed. A salivary pneumatic
      lithotripter probe was inserted through an interventional sialendoscope to
      fragment the calculi. A salivary duct catheter was then used to flush stone
      fragments, followed by endoscopy to assess complete fragmentation and ductal
      trauma. Ultimately, 7 artificial stones (3-10 mm, 4F/5F) were successfully
      fragmented without causing significant endoluminal trauma. Number of pulses for
      adequate stone fragmentation averaged 20 (range, 5-31). In all cases, stone
      fragments were successfully flushed out with the salivary duct catheter.
      Postprocedure endoscopy confirmed ductal integrity in all 7 ducts. While more
      studies are needed, this preliminary animal model demonstrates efficacy of
      endoscopic pneumatic lithotripsy for the management of sialolithiasis.

PMID- 27048663
TI  - Successful Use of Radiotherapy for Pterygopalatine Fossa Amyloidosis.

PMID- 27048664
TI  - Analysis of Outcome Domains in Adult Cochlear Implantation: A Systematic Review.
AB  - OBJECTIVES: To determine the breadth of outcome domains used in the reporting of
      adult cochlear implant surgery for the purpose of registry and quality measure
      development. DATA SOURCES: Systematic review of randomized controlled trials.
      REVIEW METHODS: In consultation with a medical librarian, search strategies were
      constructed to identify randomized controlled trials studying adults undergoing
      cochlear implantation. MEDLINE, EMBASE, Scopus, CINAHL, Cochrane Database of
      Systematic Reviews, Cochrane Central Register of Controlled Trials, and the
      Database of Abstracts of Reviews of Effects were searched from database inception
      to July 2015. Studies were evaluated for level of evidence and risk of bias with
      the Cochrane Collaboration's Risk of Bias Tool, and outcome domains were
      extracted from each study. RESULTS: Of 4473 unique citations found, 8 studies
      were included in this review. All 8 trials were evidence level 1B. Risk of bias
      was low in 2 trials and high in the other 6. Reported outcome domains included
      speech perception in quiet and noise, speech tracking, quality of life, timbre
      perception, hearing preservation, vestibular function, electrode insertion
      technique, functional measures, functional imaging, fitting time, and tinnitus.
      CONCLUSIONS: An analysis of randomized controlled trials studying cochlear
      implantation in adults yielded a wide spectrum of outcome domains. This is the
      first study to comprehensively describe the breadth of outcome domains in adult
      cochlear implantation. Validated instruments from these domains could be
      considered for potential inclusion as quality measures and registry use.

PMID- 27048665
TI  - A Systematic Review of Patient- or Proxy-Reported Validated Instruments Assessing
      Pediatric Dysphagia.
AB  - OBJECTIVE: Pediatric dysphagia occurs in 500,000 children each year; however,
      there is not a common tool to assess these children. Our aim was to identify
      validated patient- or parent-reported outcome assessment tools evaluating
      pediatric dysphagia. DATA SOURCES: Scopus, EMBASE, PubMed, Cochrane Library, and
      CINAHL electronic databases (all indexed years through August 2014). REVIEW
      METHODS: Inclusion criteria included English-language articles containing
      instruments evaluated in children. Two investigators independently reviewed all
      articles, and the review was performed according to PRISMA guidelines (Preferred
      Reporting Items for Systematic Reviews and Meta-analyses). RESULTS: The initial
      search yielded 1697 abstracts; 158 studies were assessed further. Four symptom
      questionnaires, validated in adults, were used to report pediatric dysphagia
      outcomes. Four outcomes tools assessing dysphagia were validated in pediatrics in
      selected populations. The Dysphagia in Multiple Sclerosis questionnaire and the
      Dysphagia Symptom Questionnaire for eosinophilic esophagitis were validated in
      adolescents and adults. The Symptom Questionnaire for Eosinophilic Esophagitis
      was validated in children with eosinophilic esophagitis. The Pediatric Quality of
      Life Inventory Gastrointestinal Symptoms Module, validated in children with
      gastrointestinal disorders, includes 2 domains that assess swallowing function.
      CONCLUSION: We did not identify any validated patient- or parent-reported outcome
      assessment tools examining dysphagia symptoms in a general pediatric population.
      However, we identified 4 questionnaires that have been validated in specific
      pediatric disease cohorts. Having a standardized assessment instrument validated
      in all children would allow clinicians to systematically report symptoms and
      compare results of pediatric clinical trials. With this in mind, we recommend
      establishing a standard questionnaire for the broader pediatric population.

PMID- 27048666
TI  - Informed Consent in Pediatric Otolaryngology: What Risks and Benefits Do Parents
      Recall?
AB  - OBJECTIVE: To evaluate parental recall of surgical risks and benefits in
      pediatric otolaryngology and to assess for factors that may influence recall.
      STUDY DESIGN: Prospective cohort study. SETTING: Academic pediatric
      otolaryngology clinic. SUBJECTS AND METHODS: Eighty-four parents of children <6
      years of age who underwent consultation for adeno/tonsillectomy and/or
      tympanostomy tube insertion were prospectively enrolled. Consultation visits were
      video recorded and the benefits and risks of surgery documented. Two weeks
      following the consultation, parents were contacted for assessment of recall of
      information discussed during the consultation. RESULTS: Overall, parents recalled
      only one-third of the risks of surgery mentioned by the surgeons. Parents were
      significantly more likely to recall the benefits of surgery as opposed to the
      risks (P < .001). Nine parents (10.7%) reported that no benefits were discussed
      during the consultation, and 10 (11.9%) reported no mention of any risks.
      Inconsistencies were present in which risks and benefits were mentioned by the
      providers. Parents who decided to proceed with surgery (58.3%) were significantly
      less likely to recall the surgical risks than those who did not (P < .001). The
      specific surgeon involved, the number of caregivers present, parental education
      level, and prior surgical history did not influence recall. CONCLUSION: Parental
      recall of benefits and risks associated with common pediatric otolaryngology
      procedures was poor. This information is important because a low rate of recall
      may influence parents' perspectives of the procedure and could alter their
      decision-making processes or expectations. Methods to improve parental recall
      should be further studied.

PMID- 27048667
TI  - Pediatric Posttonsillectomy Hemorrhage: Demographic and Geographic Variation in
      Health Care Costs in the United States.
AB  - OBJECTIVE: To examine variations in management of pediatric posttonsillectomy
      hemorrhage and associated costs from a national third-party payer perspective.
      STUDY DESIGN: The MarketScan database was analyzed for claims made for 30 days
      following tonsillectomy/adenotonsillectomy between 2008 and 2012 for privately
      insured children aged 1 to 17 years. Costs for management of postoperative
      hemorrhage by age, sex, and region were calculated in addition to total costs
      incurred for 30 days postoperatively. SETTING: MarketScan database. SUBJECTS AND
      METHODS: Database study. RESULTS: A total of 305,860 children were included.
      Overall, 0.3% had a postoperative bleed that required treatment but not surgical
      intervention or admission for hospitalization; 0.2% had one that required
      hospitalization; and 0.8% had one that required surgical intervention. The mean
      30-day costs were $7660 for postoperative bleed that required surgery or
      hospitalization, $4580 for outpatient treatment, and $370 for no postoperative
      bleed. Children between 11 and 17 years old were most likely to have
      interventions for postoperative bleeding but had the lowest mean costs for them
      ($7320 for hospital based, $3860 for outpatient). There were regional differences
      in costs for in-patient management of bleeds, with highest costs in the West,
      with a mean of $8850, versus the South, with a mean of $7160. CONCLUSIONS: There
      are geographic and demographic variations in managing pediatric posttonsillectomy
      hemorrhage and in the costs associated with management on a national level.

PMID- 27048668
TI  - Effects of Nasal Septum Deviation and Septoplasty on Cardiac Arrhythmia Risk.
AB  - OBJECTIVE: Upper airway obstruction (UAO) can result in cardiac complications,
      including arrhythmias and sudden cardiac death. Nasal septum deviation (NSD) is a
      common cause of UAO. The aim of this study was to assess the risk of cardiac
      arrhythmias in patients with NSD. To assess this risk, we measured noninvasive
      indicators of atrial arrhythmia (P-wave dispersion [Pd]) and ventricular
      arrhythmia (corrected QT dispersion [QTcd]) and compared these values between NSD
      patients and healthy subjects. STUDY DESIGN: Prospective study. SETTINGS:
      Tertiary referral center. SUBJECTS AND METHODS: This study included 53
      consecutive patients who had underwent septoplasty due to marked NSD.
      Electrocardiographic records were used to determine Pd and QTcd values
      preoperatively and 6 months postoperatively. Fifty-three consecutive age- and sex
      matched subjects without any UAO were also examined as a control group. RESULTS:
      Preoperative Pd and QTcd values were significantly higher in NSD patients than in
      the control group (Pd: 57.40 +/- 14.21 vs 34.11 +/- 7.12 milliseconds, P < .001;
      QTcd: 81.77 +/- 16.39 vs 50.25 +/- 11.51 milliseconds, P < .001, respectively).
      In addition, Pd and QTcd values were significantly greater in preoperative NSD
      patients when compared with the same patients postoperatively (Pd: 57.40 +/-
      14.21 vs 36.32 +/- 8.9 milliseconds, P = .013; QTcd: 81.77 +/- 16.39 vs 55.76 +/-
      11.4 milliseconds, P = .012, respectively). CONCLUSION: In conclusion, NSD
      patients are at risk for both atrial and ventricular cardiac arrhythmias;
      however, septoplasty in these patients can relieve UAO and reduce the risk of
      arrhythmias.

PMID- 27048669
TI  - Computational Modeling of Airway Obstruction in Sleep Apnea in Down Syndrome: A
      Feasibility Study.
AB  - Current treatment options are successful in 40% to 60% of children with
      persistent obstructive sleep apnea after adenotonsillectomy. Residual obstruction
      assessments are largely subjective and do not clearly define multilevel
      obstruction. We endeavor to use computational fluid dynamics to perform virtual
      surgery and assess airflow changes in patients with Down syndrome and persistent
      obstructive sleep apnea. Three-dimensional airway models were reconstructed from
      respiratory-gated computed tomography and magnetic resonance imaging. Virtual
      surgeries were performed on 10 patients, mirroring actual surgeries. They
      demonstrated how surgical changes affect airflow resistance. Airflow and upper
      airway resistance was calculated from computational fluid dynamics. Virtual and
      actual surgery outcomes were compared with obstructive apnea-hypopnea index
      values. Actual surgery successfully treated 6 of 10 patients (postoperative
      obstructive apnea-hypopnea index <5). In 8 of 10 subjects, both apnea-hypopnea
      index and the calculated upper airway resistance after virtual surgery decreased
      as compared with baseline values. This is a feasibility and proof-of-concept
      study. Further studies are needed before using these techniques in surgical
      planning.

PMID- 27048670
TI  - Randomized Trial of Vitamin C/E Complex for Prevention of Radiation-Induced
      Xerostomia in Patients with Head and Neck Cancer.
AB  - OBJECTIVE: The present study was conducted to determine the preventive efficacy
      of vitamin C/E complex supplementation for radiotherapy (RT)-induced xerostomia
      in patients with head and neck cancer. STUDY DESIGN: Prospective, double-blinded,
      randomized, placebo-controlled study. SETTING: A single tertiary referral
      institution. SUBJECTS AND METHODS: The trial group (n = 25) received antioxidant
      supplements (100 IU of vitamin E + 500 mg of vitamin C) twice per day during RT,
      while the control group (n = 20) received an identical placebo. Pre-RT and 1 and
      6 months post-RT, patient-reported xerostomia questionnaires, observer-rated
      xerostomia score, and salivary scintigraphy were serially obtained to compare
      xerostomia severity between the 2 groups. RESULTS: The trial group showed greater
      improvements in xerostomia questionnaire and score at 6 months post-RT when
      compared with those at 1 month post-RT (P = .007 and .008, respectively). In
      contrast, the control group showed no changes between 1 and 6 months post-RT. By
      salivary scintigraphy, there was no difference in maximal accumulation or
      ejection fraction between the 2 groups. However, the trial group maintained
      significantly better oral indices at the prestimulatory (P = .01) and
      poststimulatory (P = .009) stages at 1 month post-RT, compared with the control
      group. At the final follow-up, there was no difference in overall survival and
      disease-free survival between the 2 groups. CONCLUSIONS: Our data suggest that
      short-term supplementation with an antioxidant vitamin E/C complex exerts a
      protective effect against RT-induced xerostomia.

PMID- 27048671
TI  - Computer-Aided Design and 3D Printing to Produce a Costal Cartilage Model for
      Simulation of Auricular Reconstruction.

PMID- 27048672
TI  - In-Office Secondary Tracheoesophageal Puncture with Immediate Prosthesis
      Placement.

PMID- 27048673
TI  - Pediatric Oral Electrical Burns: Incidence of Emergency Department Visits in the
      United States, 1997-2012.
AB  - OBJECTIVES: To investigate the epidemiology of emergency department visits for
      pediatric patients presenting with electrical burns to the mouth. STUDY DESIGN:
      Cross-sectional analysis of a national database. SETTING: National Electronic
      Injury Surveillance System Database. SUBJECTS AND METHODS: The Consumer Product
      Safety Commission's National Electronic Injury Surveillance System database was
      used to derive a national weighted estimate of emergency department visits for
      oral electrical burns and was queried for each patient's age, sex, race, local of
      incidence, disposition, and related consumer product. RESULTS: There were an
      estimated 1042 emergency department visits for pediatric oral electrical burns
      from 1997 to 2012, or an average of approximately 65.1 cases per year. A total of
      59.6% of patients were male. Nearly half of emergency department visits involved
      patients <3 years of age, and more than three-fourths of emergency department
      visits involved patients <5 years of age. A total of 77.2% of patients were
      examined, treated, and released from the emergency department, while 19.2% were
      admitted to the hospital. Most injuries involved electrical outlets or
      receptacles (10.8%), extension cords (18.5%), and electrical wires (21.5%).
      CONCLUSION: Earlier incidence estimates of pediatric oral electrical burns varied
      substantially within the literature and varied from small case reports to single
      year studies. Our multiyear data analysis provides evidence of decreasing annual
      incidence when compared with historical estimates for a common but potentially
      morbid injury among the pediatric population.

PMID- 27048674
TI  - Retromaxillary Pneumatization of Posterior Ethmoid Air Cells: Novel Description
      and Surgical Implications.
AB  - OBJECTIVE: Retromaxillary pneumatization of posterior ethmoid (PE) air cells is
      an area that is yet to have appropriate description in rhinologic literature.
      STUDY DESIGN: Case series with chart review. SETTING: Tertiary care hospital.
      SUBJECTS AND METHODS: First, 524 sides in 262 paranasal sinus computed tomography
      scans were analyzed: 350 normal sides were examined for PE pneumatization lateral
      to the sagittal plane of the medial wall of maxillary sinus posteriorly, and 174
      diseased sides were similarly reviewed to check how pathology may affect
      identification and measurements. Following that, 153 operated sides in 84 cases
      prepared for revision endoscopic sinus surgery (ESS) were studied for residual
      diseased cells at different anatomic locations. RESULTS: Overall, retromaxillary
      PE pneumatization was identifiable in 416 of the 524 sides (79.4%). Lateral
      retromaxillary extension varied from 0.5 to 12.3 mm (mean +/- SD, 4.8 +/- 2.3
      mm). This area of pneumatization is bounded anteroinferiorly by the junction
      between the posterior and superior walls of the maxillary sinus. Three cell types
      were described depending on the degree of lateral extension (type I, <3 mm; type
      II, 3-6 mm; type III, >6 mm). This cell, which we refer to as the Herzallah cell,
      was distinguishable from the anterior ethmoid Haller cell and was found to have
      residual disease in 50.3% of cases prepared for revision ESS. CONCLUSION:
      Retromaxillary extension of PE air cells varies considerably and requires
      attention during ESS. Residual undissected retromaxillary cell is a common
      finding in revision ESS and can contribute to inadequate disease clearance.

PMID- 27048675
TI  - A Low-Cost Method of Ciliary Beat Frequency Measurement Using iPhone and MATLAB:
      Rabbit Study.
AB  - OBJECTIVES: (1) To determine ciliary beat frequency (CBF) using a consumer-grade
      cellphone camera and MATLAB and (2) to evaluate the effectiveness and accuracy of
      the proposed method. STUDY DESIGN: Prospective animal study. SETTING: Academic
      otolaryngology department research laboratory. METHODS: Five ex vivo tracheal
      samples were extracted from 3 freshly euthanized (<3 hours postmortem) New
      Zealand white rabbits and incubated for 30 minutes in buffer at 23 degrees C,
      buffer at 37 degrees C, or 10% formalin at 23 degrees C. Samples were sectioned
      transversely and observed under a phase-contrast microscope. Cilia movement was
      recorded through the eyepiece using an iPhone 6 at 240 frames per second (fps).
      Through MATLAB programming, the video of the 23 degrees C sample was downsampled
      to 120, 60, and 30 fps, and Fourier analysis was performed on videos of all frame
      rates and conditions to determine CBF. CBF of the 23 degrees C sample was also
      calculated manually frame by frame for verification. RESULTS: Recorded at 240
      fps, the CBF at 23 degrees C was 5.03 +/- 0.4 Hz, and the CBF at 37 degrees C was
      9.08 +/- 0.49 Hz (P < .001). The sample with 10% formalin did not display any
      data beyond DC noise. Compared with 240 fps, the means of other frame
      rates/methods (120, 60, 30 fps; manual counting) at 23 degrees C all showed no
      statistical difference (P > .05). CONCLUSION: There is no significant difference
      between CBF measured via visual inspection and that analyzed by the developed
      program. Furthermore, all tested acquisition rates are shown to be effective,
      providing a fast and inexpensive alternative to current CBF measurement
      protocols.

PMID- 27048676
TI  - Neural Mechanisms Contributing to Dysphagia in Mouse Models.
AB  - Investigative research into curative treatments for dysphagia is hindered by our
      incomplete understanding of the neural mechanisms of swallowing in health and
      disease. Development of translational research models is essential to bridge this
      knowledge gap by fostering innovative methodology. Toward this goal, our
      laboratory has developed a translational research assessment tool to investigate
      the neural mechanistic control of swallowing in unrestrained, self-feeding mice.
      Here we describe our initial development of synchronous brainstem neural
      recordings with a videofluoroscopic swallow study assay in healthy mice across
      the life span. Refinement of this combined methodology is currently underway.
      Ultimately, we envision that this assessment tool will permit systematic analysis
      of therapeutic interventions for dysphagia in preclinical trials with numerous
      mouse models of human conditions that cause dysphagia, such as amyotrophic
      lateral sclerosis, Parkinson's disease, stroke, and advanced aging.

PMID- 27048677
TI  - Prognostic Factors in Myoepithelial Carcinoma of the Major Salivary Glands.
AB  - OBJECTIVES: (1) Identify all cases of myoepithelial carcinoma of the major
      salivary glands from the National Cancer Data Base (NCDB). (2) Analyze the effect
      of grade, stage, and regional nodal metastasis on survival in myoepithelial
      carcinoma of the major salivary glands. STUDY DESIGN: Retrospective review of
      NCDB. SETTING: Multicenter data pooled from 1998 to 2012 in the NCDB. METHODS: We
      identified all reported cases of myoepithelial carcinomas of the major salivary
      glands from the United States from 1998 to 2012 in the NCDB. Clinical parameters
      were then examined and analyzed for predictors of survival. RESULTS: A total of
      473 cases of myoepithelial carcinoma were identified. Of the reported cases,
      38.1% were low grade; 26.7%, intermediate grade; and 35.2%, high grade. When
      presenting stage was examined, 24.4% were stage I; 30.6%, stage II; 22.5%, stage
      III; 12.2%, stage IVa; 3.0%, stage IVb; and 4.1%, stage IVc. At presentation,
      18.7% of patients had regional nodal disease, and 4.5% had distant metastases.
      The 3- and 5-year survival rates were 73% and 64%, respectively. The presence of
      nodal disease significantly reduced mean survival time versus those without (64
      vs 108 months, P < .001), as did high-grade disease compared with low grade (67
      vs 114 months, P < .001) and stage III/IV compared with stage I/II disease (61 vs
      118 months, P < .001). CONCLUSIONS: The presence of regional nodal disease, high
      grade disease, and advanced stage are predictors of lower survival in
      myoepithelial carcinoma. Further studies based on types of treatment are
      warranted.

PMID- 27048678
TI  - Laryngopharyngeal Reflux Has Negative Effects on Taste and Smell Functions.
AB  - OBJECTIVE: We evaluated the halimetric, olfactory, and taste functions of
      patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective clinical
      study. SETTING: Multicenter tertiary care hospital. METHODS: Patients who were
      diagnosed with LPR for the first time on the basis of a Reflux Finding Score
      (RFS) >11 and a Reflux Symptom Index (RSI) >13 were enrolled in this study. A
      control group was selected from patients without a complaint of LPR. OralChroma
      was used for the halimetric measurement; Sniffin' Sticks were used for the
      smelling test; Taste Strips were used for the taste test; and monosodium L
      glutamate was used for the umami test. RESULTS: A total of 110 subjects were
      included, with a mean age of 36.8 +/- 10 years (range, 19-57 years). The
      differences in odor threshold scores were significant between the groups (P <
      .001), but no change was detected for the odor identification or discrimination
      scores between the groups. Bitter taste scores were significantly diminished in
      the reflux group compared with those in the control group (P = .001), whereas no
      impairments were found in the other taste scores (sweet, salty, and sour). The
      reflux group had significantly higher umami taste scores than those of the
      control group for the posterior tongue and soft palate anatomic sites (P < .001
      and P < .001, respectively). Dimethyl sulfite levels were significantly higher in
      the reflux group than in the control (P = .001). CONCLUSION: Questioning patients
      who present with halitosis, taste, or smelling disorders is important to diagnose
      LPR.

PMID- 27048679
TI  - This isn't going to end well: Fictional representations of medical research in
      television and film.
AB  - Fictional television shows and films convey cultural assumptions about scientists
      and the research enterprise. But how do these forms of entertainment portray
      medical research participants? We sampled 65 television shows and films released
      between 2004 and 2014 to determine the ways in which medical research and human
      participants are represented in popular media. We found that research
      participants are largely represented as White, male, and lower or working class
      and that 40% of the participants depicted in these fictional accounts were
      seeking financial compensation, 34% were hoping for a therapeutic benefit, and
      15% were coerced into participation. Regardless of participant motivation, media
      representations tended to portray a negative outcome of medical research.
      Interpreting the themes in these media, we argue that these fictional portrayals
      might provide the public with valuable representations of medical research,
      especially in terms of risks to research participants, scientific failure, and
      researchers' conflicts of interest.

PMID- 27048680
TI  - Laparoscopic versus Open Surgery for Acute Adhesive Small-Bowel Obstruction: A
      Propensity Score-Matched Analysis.
AB  - BACKGROUND AND AIMS: The laparoscopic approach has been increasingly used to
      treat adhesive small-bowel obstruction. The aim of this study was to compare the
      outcomes of a laparoscopic versus an open approach for adhesive small-bowel
      obstruction. MATERIAL AND METHODS: Data were retrospectively collected on
      patients who had surgery for adhesive small-bowel obstruction at a single
      academic center between January 2010 and December 2012. Patients with a
      contraindication for the laparoscopic approach were excluded. A propensity score
      was used to match patients in the laparoscopic and open surgery groups based on
      their preoperative parameters. RESULTS: A total of 25 patients underwent
      laparoscopic adhesiolysis and 67 patients open adhesiolysis. The open
      adhesiolysis group had more suspected bowel strangulations and more previous
      abdominal surgeries than the laparoscopic adhesiolysis group. Severe complication
      rate (Clavien-Dindo 3 or higher) was 0% in the laparoscopic adhesiolysis group
      versus 14% in the open adhesiolysis group ( p = 0.052). Twenty-five propensity
      score-matched patients from the open adhesiolysis group were similar to
      laparoscopic adhesiolysis group patients with regard to their preoperative
      parameters. Length of hospital stay was shorter in the laparoscopic adhesiolysis
      group compared to the propensity score-matched open adhesiolysis group (6.0 vs
      10.0 days, p = 0.037), but no differences were found in severe complications
      between the laparoscopic adhesiolysis and propensity score-matched open
      adhesiolysis groups (0% vs 4%, p = 0.31). CONCLUSION: Patients selected to be
      operated by the open approach had higher preoperative morbidity than the ones
      selected for the laparoscopic approach. After matching for this disparity, the
      laparoscopic approach was associated with a shorter length of hospital stay
      without differences in complications. The laparoscopic approach may be a
      preferable approach in selected patients.

PMID- 27048681
TI  - Continuous time Markov chain approaches for analyzing transtheoretical models of
      health behavioral change: A case study and comparison of model estimations.
AB  - Continuous time Markov chain models are frequently employed in medical research
      to study the disease progression but are rarely applied to the transtheoretical
      model, a psychosocial model widely used in the studies of health-related
      outcomes. The transtheoretical model often includes more than three states and
      conceptually allows for all possible instantaneous transitions (referred to as
      general continuous time Markov chain). This complicates the likelihood function
      because it involves calculating a matrix exponential that may not be simplified
      for general continuous time Markov chain models. We undertook a Bayesian approach
      wherein we numerically evaluated the likelihood using ordinary differential
      equation solvers available from the gnu scientific library. We compared our
      Bayesian approach with the maximum likelihood method implemented with the R
      package MSM. Our simulation study showed that the Bayesian approach provided more
      accurate point and interval estimates than the maximum likelihood method,
      especially in complex continuous time Markov chain models with five states. When
      applied to data from a four-state transtheoretical model collected from a
      nutrition intervention study in the next step trial, we observed results
      consistent with the results of the simulation study. Specifically, the two
      approaches provided comparable point estimates and standard errors for most
      parameters, but the maximum likelihood offered substantially smaller standard
      errors for some parameters. Comparable estimates of the standard errors are
      obtainable from package MSM, which works only when the model estimation algorithm
      converges.

PMID- 27048682
TI  - Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated
      high-grade serous ovarian cancer.
AB  - AIMS: BRCA1 mutation carriers are at increased risk of developing high-grade
      serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube
      epithelium. We aimed to identify differentially expressed known and novel miRNAs
      in BRCA1-associated HGSOC. METHODS: Small RNA sequencing was performed on eight
      normal tubal and five HGSOC samples of BRCA1 carriers. Differential expression of
      a subset of known and novel miRNAs was validated by qRT-PCR on the samples used
      for small RNA sequencing and a second sample cohort comprising normal and HGSOC
      tissue of matched BRCA1 and non-BRCA carriers. Data from The Cancer Genome Atlas
      were used to determine the clinical relevance of the validated differentially
      expressed miRNAs. RESULTS: 59 known and 20 novel miRNAs showed a significant
      >fourfold expression difference between normal tubal tissue and HGSOC. qRT-PCR
      validation confirmed a significant difference in expression levels for 10 out of
      11 known miRNAs. Upregulation of two novel miRNAs could not be confirmed.
      Interestingly, for seven miRNAs a significant increase in expression was observed
      when comparing normal tubal tissue of postmenopausal women with premenopausal
      women. Expression levels of miR-145-5p significantly increased with International
      Federation of Gynecology and Obstetrics stage, while the expression levels of the
      other nine validated miRNAs were not associated with clinical characteristics.
      CONCLUSIONS: We report a comprehensive expression signature including both known
      and novel miRNAs of BRCA1-associated HGSOC. Comparison with previous profiling
      studies showed a good overlap and a large number of miRNAs not reported to be
      differentially expressed in HGSOC before underscoring the importance of this
      study.

PMID- 27048683
TI  - An interview with Cheryll Tickle.
AB  - Cheryll Tickle is an Emeritus Professor at the University of Bath, UK. She
      dedicated her long research career mainly to the study of limb development in the
      chick, and has received numerous awards for her contributions to science,
      including being elected a Fellow of The Royal Society and receiving a CBE from
      the Queen. This year the British Society for Developmental Biology (BSDB) has
      created a new award in her honour, the Cheryll Tickle Medal, to be awarded to a
      mid-career, female scientist for outstanding achievements in the field. We asked
      Cheryll what this award means to her and how science has changed during her
      career. 

PMID- 27048684
TI  - An interview with Abigail Tucker.
AB  - Abigail Tucker is a professor at King's College London, UK and her lab works on
      various aspects of craniofacial development - from basic, evolutionary and
      clinical biology perspectives. This year, Abigail will be awarded the first
      Cheryll Tickle Medal by the British Society for Developmental Biology (BSDB). We
      chatted with Abigail about her research, her commitment to public engagement and
      the challenges and rewards of working with emerging model systems. 

PMID- 27048685
TI  - Lineage specification in the mouse preimplantation embryo.
AB  - During mouse preimplantation embryo development, totipotent blastomeres generate
      the first three cell lineages of the embryo: trophectoderm, epiblast and
      primitive endoderm. In recent years, studies have shown that this process appears
      to be regulated by differences in cell-cell interactions, gene expression and the
      microenvironment of individual cells, rather than the active partitioning of
      maternal determinants. Precisely how these differences first emerge and how they
      dictate subsequent molecular and cellular behaviours are key questions in the
      field. As we review here, recent advances in live imaging, computational
      modelling and single-cell transcriptome analyses are providing new insights into
      these questions. 

PMID- 27048686
TI  - Stars from the darkest night: unlocking the neurogenic potential of astrocytes in
      different brain regions.
AB  - In a few regions of the adult brain, specialized astrocytes act as neural stem
      cells capable of sustaining life-long neurogenesis. In other, typically non
      neurogenic regions, some astrocytes have an intrinsic capacity to produce neurons
      when provoked by particular conditions but do not use this ability to replace
      neurons completely after injury or disease. Why do astrocytes display regional
      differences and why do they not use their neurogenic capacity for brain repair to
      a greater extent? In this Review, we discuss the neurogenic potential of
      astrocytes in different brain regions and ask what stimulates this potential in
      some regions but not in others. We discuss the transcriptional networks and
      environmental cues that govern cell identity, and consider how the activation of
      neurogenic properties in astrocytes can be understood as the de-repression of a
      latent neurogenic transcriptional program. 

PMID- 27048687
TI  - Kinesin-1 tail autoregulation and microtubule-binding regions function in
      saltatory transport but not ooplasmic streaming.

PMID- 27048688
TI  - Effect of high sedimentation rates on surface sediment dynamics and mangrove
      growth in the Porong River, Indonesia.
AB  - Large quantities of mud from the LUSI (Lumpur Sidoarjo) volcano in northeastern
      Java have been channeled to the sea causing high rates of sediment delivery to
      the mouth of the Porong River, which has a cover of natural and planted
      mangroves. This study investigated how the high rates of sediment delivery
      affected vertical accretion, surface elevation change and the growth of Avicennia
      sp., the dominant mangrove species in the region. During our observations in 2010
      2011 (4-5years after the initial volcanic eruption), very high rates of
      sedimentation in the forests at the mouth of the river gave rise to high vertical
      accretion of over 10cmy(-1). The high sedimentation rates not only resulted in
      reduced growth of Avicennia sp. mangrove trees at the two study sites at the
      Porong River mouth, but also gave rise to high soil surface elevation gains. 

PMID- 27048689
TI  - The role of social marketing, marine turtles and sustainable tourism in reducing
      plastic pollution.
AB  - Environmental plastic pollution constitutes a significant hazard to marine
      turtles, human health and well-being. We describe a transdisciplinary approach to
      draw together findings from diverse disciplines in order to highlight key
      environmental pollution problems and their consequences, together with social
      marketing-based strategies to address the problems. The example of plastic
      pollution and impacts to marine turtles illustrates the severity of the problem.
      Wildlife tourism and sustainable tourism activity have not focussed on specific
      behaviours to change and have had minimal impact on subsequent human behaviour
      regarding environmental issues, indicating the need for new strategies. Social
      marketing principles offer promise, but there is a need to investigate the
      utility of various theoretical foundations to aid the design and implementation
      of interventions. We offer insight towards using sophisticated multi-method
      research to develop insights into behaviours and segmentation-based strategies,
      that can aid the identification of barriers to, and enablers of, sustained
      behaviour change. 

PMID- 27048690
TI  - Sampling of Ostreopsis cf. ovata using artificial substrates: Optimization of
      methods for the monitoring of benthic harmful algal blooms.
AB  - In the framework of monitoring of benthic harmful algal blooms (BHABs), the most
      commonly reported sampling strategy is based on the collection of macrophytes.
      However, this methodology has some inherent problems. A potential alternative
      method uses artificial substrates that collect resuspended benthic cells. The
      current study defines main improvements in this technique, through the use of
      fiberglass screens during a bloom of Ostreopsis cf. ovata. A novel set-up for the
      deployment of artificial substrates in the field was tested, using an easy clip
      in system that helped restrain substrates perpendicular to the water flow. An
      experiment was run in order to compare the cell collection efficiency of
      different mesh sizes of fiberglass screens and results suggested an optimal
      porosity of 1-3mm. The present study goes further on showing artificial
      substrates, such as fiberglass screens, as efficient tools for the monitoring and
      mitigation of BHABs. 

PMID- 27048691
TI  - Endovascular pure electrocoagulation of intracranial perforator blister-like
      aneurysm not accessible to microcatheter-New approach to treat small vessel
      hemorrhage disease.

PMID- 27048692
TI  - Treatment in patients who are not eligible for intravenous alteplase: MR CLEAN
      subgroup analysis.
AB  - BACKGROUND AND PURPOSE: Patients with acute ischemic stroke due to intracranial
      large vessel occlusion benefit from intra-arterial therapy. Uncertainty exists
      about the effect of intra-arterial therapy in patients with contraindications for
      treatment with intravenous alteplase treatment. Our aim was to describe the
      clinical characteristics of this subgroup of patients and whether intra-arterial
      therapy is as safe and effective as it is after intravenous alteplase treatment.
      METHODS: All 500 MR CLEAN patients were included and we distinguished between
      patients who were and were not treated with intravenous alteplase treatment. We
      estimated the effect of intra-arterial therapy on the shift on the modified
      Rankin Scale score with ordinal logistic regression analysis and tested for
      interaction of intravenous alteplase treatment with intra-arterial therapy on
      outcome. Furthermore, safety parameters and serious adverse events were analyzed.
      RESULTS: Fifty-five patients (11%) were not treated with intravenous alteplase
      treatment, mostly because of prolonged coagulation time tests or recent surgery.
      These patients were older and more often had atrial fibrillation or other
      vascular comorbidity. There was no interaction between intravenous alteplase
      treatment and intervention effect (p = 0.927). Intra-arterial therapy effect size
      in patients without intravenous alteplase treatment was 2.06 [95% CI: 0.69-6.13]
      and in patients with intravenous alteplase treatment 1.71 [95% CI: 1.22-2.40].
      There were no safety issues. CONCLUSIONS: For patients with acute ischemic
      anterior circulation stroke caused by intracranial large vessel occlusion, who
      have contraindications for intravenous alteplase, intra-arterial treatment is not
      less effective or less safe than in patients who receive the treatment after
      intravenous alteplase. CLINICAL TRIAL REGISTRATION: Clinical trial registration
      URL: http://www.trialregister.nl. Unique identifier: (NTR)1804.Clinical trial
      registration-URL: http://www.controlled-trials.com. Unique identifier:
      ISRCTN10888758.

PMID- 27048693
TI  - Tenecteplase versus alteplase in stroke thrombolysis: An individual patient data
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Tenecteplase, a modified plasminogen activator with higher fibrin
      specificity and longer half-life, may have advantages over alteplase in acute
      ischemic stroke thrombolysis. AIMS: We undertook an individual patient data meta
      analysis of randomized controlled trials that compared alteplase with
      tenecteplase in acute stroke. METHODS: Eligible studies were identified by a
      MEDLINE search, and individual patient data were acquired. We compared clinical
      outcomes including modified Rankin Scale at three months, early neurological
      improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral
      hemorrhage, and mortality at three months between all dose tiers of tenecteplase
      and alteplase. RESULTS: Three relevant studies (Haley et al., Parsons et al., and
      ATTEST) included 291 patients and investigated three doses of tenecteplase (0.1,
      0.25, 0.4 mg/kg). There were no differences between any dose of tenecteplase and
      alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had
      the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5,
      7.2], p = 0.093), excellent functional outcome (modified Rankin Scale 0-1) at
      three months (OR [95%CI] 1.9 [0.8, 4.4], p = 0.28), with reduced odds of
      intracerebral hemorrhage (OR [95%CI] 0.6 [0.2, 1.8], P = 0.43) compared with
      alteplase. Only 19 patients were treated with tenecteplase 0.4 mg/kg, which
      showed increased odds of symptomatic intracerebral hemorrhage compared with
      alteplase (OR [95% CI] 6.2 [0.7, 56.3]). CONCLUSIONS: While no significant
      differences between tenecteplase and alteplase were found, point estimates
      suggest potentially greater efficacy of 0.25 and 0.1 mg/kg doses with no
      difference in symptomatic intracerebral hemorrhage, and potentially higher
      symptomatic intracerebral hemorrhage risk with the 0.4 mg/kg dose. Further
      investigation of 0.25 mg/kg tenecteplase is warranted.

PMID- 27048695
TI  - Reference intervals for thyroid hormones on Advia Centaur derived from three
      reference populations and a review of the literature.
AB  - INTRODUCTION: Laboratories are recommended to determine their own local reference
      intervals (RIs) to embrace the variations in local populations. We have assessed
      local RIs for thyroid function tests using two different approaches to selection
      of reference populations and also searched the literature for studies using the
      Advia Centaur methods. METHODS: Two independent populations were made of
      redundant serum samples from primary care in which exclusion criteria were used
      to reduce the inclusion of patients with thyroid disease. A further population of
      healthy subjects were recruited. All groups were restricted to 18-65 years and
      thyroid peroxidase antibodies (TPOabs) positive subjects were excluded. All
      samples were analysed using Advia Centaur reagents. A literature search was made
      for RI studies on non-pregnant adults using Advia Centaur. RESULTS: Redundant
      data sets consisted of 219 and 222 subjects and a healthy population of 280.
      Comparison of variance of all three groups showed differences for free T4 (fT4)
      and total T3 (TT3) (analysis of variance P < 0.0001) but thyroid-stimulating
      hormone (TSH) was similar across all three groups (P = 0.7656). RI for TSH, fT4
      and TT3 all fell within the 95% confidence interval for each other for all three
      analytes. Published RIs give wide variation although their mean is similar to the
      prospective data reported here. DISCUSSION: Our data suggest that a consensus set
      of RIs for Advia Centaur can be adopted from the prospective studies and
      literature search in this paper and we would suggest the following RIs: TSH 0.5
      4.4 mIU/L; fT4 10-20 pmol/L; and TT3 1.1-2.4 nmol/L.

PMID- 27048694
TI  - Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage:
      Protocol for a randomized, placebo-controlled trial.
AB  - RATIONALE: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid
      is easy to administer, readily available, inexpensive, and effective in other
      hemorrhagic conditions. AIM: This randomized trial aims to test the hypothesis
      that intravenous tranexamic acid given within 8 h of spontaneous intracerebral
      hemorrhage reduces death or dependency. DESIGN: Phase III prospective double
      blind randomized placebo-controlled trial. Participants within 8 h of spontaneous
      intracerebral hemorrhage are randomized to receive either intravenous tranexamic
      acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. SAMPLE SIZE
      ESTIMATES: A trial of 2000 participants (300 from start-up phase and 1700 from
      main phase) will have 90% power to detect an ordinal shift of the modified Rankin
      Scale with odds ratio 0.79. STUDY OUTCOMES: The primary outcome is death or
      dependency measured by ordinal shift analysis of the 7 level mRS at day 90.
      Secondary outcomes are neurological impairment at day 7 and disability, quality
      of life, cognition, and mood at day 90. Safety outcomes are death, serious
      adverse events, thromboembolic events, and seizures. Cost outcomes are length of
      stay in hospital, readmission, and institutionalization. DISCUSSION: This
      pragmatic trial is assessing efficacy of tranexamic acid after spontaneous
      intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016
      1355 participants have been enrolled, from 95 centers in seven countries.
      Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.

PMID- 27048696
TI  - Educational Attainment and Women's Environmental Mastery in Midlife: Findings
      From a British Birth Cohort Study.
AB  - Using data from 1,184 women in the MRC National Survey of Health and Development,
      we estimated associations between education and Ryff's environmental mastery
      scale scores at age 52. Confirmatory factor analysis indicated two subscales,
      here termed mastery skills and mastery accomplishments. Low education was
      associated with higher mastery skills. This was partly explained by childhood
      socioeconomic position, as mastery was lower among those with fathers in the most
      and least advantaged occupational classes. Education was not associated with
      mastery accomplishments in unadjusted models. Lower ambitions for family/home
      were associated with higher mastery accomplishments and may have partly
      suppressed as an association between education and mastery accomplishments. This
      study highlights childhood as well as adult correlates of mastery and adds to
      mounting evidence that higher mastery is not universally found among those who
      are more educated.

PMID- 27048697
TI  - National Analysis of 2454 Pediatric Moyamoya Admissions and the Effect of
      Hospital Volume on Outcomes.
AB  - BACKGROUND AND PURPOSE: Comprehensive multicenter data on treatment of pediatric
      moyamoya in the United States is lacking. We sought to identify national trends
      in the diagnosis and treatment of this disease. METHODS: A total of 2454 moyamoya
      admissions from 1997 to 2012 were identified from the Kids Inpatient Database.
      Demographics, inpatient costs, interventions, and discharge status were analyzed.
      Admissions with and without surgical revascularization were reviewed separately.
      The effect of hospital moyamoya volume on outcomes was analyzed by multivariate
      regression analysis. RESULTS: Care of moyamoya patients has been concentrating at
      high-volume centers during the past 12 years. Among moyamoya admission without
      surgical revascularization, high-volume hospitals show no difference in length of
      stay, cost, or complications compared with low-volume centers. However, low
      volume hospitals have more nonroutine discharges (odds ratio, 2.32; P=0.0005) and
      inpatient deaths (odds ratio, 12.7; P=0.02) when no revascularization was
      performed. In contrast, among admissions with surgical revascularization, high
      volume centers had decreased length of stay (4.7 versus 6.2 days; P=0.004),
      reduced cost ($88 000 versus $138 000; P<0.0001), and no increase in
      complications (P=0.29) compared with low-volume centers. Admissions with
      revascularization to low-volume hospitals also had increased likelihood of
      nonroutine discharge (odds ratio, 8.23; P=0.02) compared with high-volume
      centers. CONCLUSIONS: This is the largest study of US pediatric moyamoya
      admissions to date. These data demonstrate that volume correlates with outcome,
      indicating high-volume centers provide significantly improved care and reduced
      mortality in pediatric moyamoya patients, with the most marked benefit observed
      in admissions for surgical revascularization.

PMID- 27048698
TI  - Features and Determinants of Lacune Shape: Relationship With Fiber Tracts and
      Perforating Arteries.
AB  - BACKGROUND AND PURPOSE: Lacunes are a major manifestation of cerebral small
      vessel disease. Although still debated, the morphological features of lacunes may
      offer mechanistic insights. We systematically analyzed the shape of incident
      lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy, a genetically defined small vessel disease. METHODS: A total
      of 88 incident lacunes from 57 patients were segmented from 3-dimensional T1
      magnetic resonance images and 3 dimensionally reconstructed. Anatomic location,
      diameter, volume, surface area, and compactness of lacunes were assessed. The
      shape was analyzed using a size, orientation, and position invariant spectral
      shape descriptor. We further investigated the relationship with perforating
      arteries and fiber tracts. RESULTS: Lacunes were most abundant in the centrum
      semiovale and the basal ganglia. Diameter, volume, and surface area of lacunes in
      the basal ganglia and centrum semiovale were larger than in other brain regions.
      The spectral shape descriptor revealed a continuum of shapes with no evidence for
      distinct classes of lacunes. Shapes varied mostly in elongation and planarity.
      The main axis and plane of lacunes were found to align with the orientation of
      perforating arteries but not with fiber tracts. CONCLUSIONS: Elongation and
      planarity are the primary shape principles of lacunes. Their main axis and plane
      align with perforating arteries. Our findings add to current concepts on the
      mechanisms of lacunes.

PMID- 27048699
TI  - Commentary on the Cervical Artery Dissection in Stroke Study Trial.

PMID- 27048700
TI  - Minimally Invasive Surgery for Intracerebral and Intraventricular Hemorrhage:
      Rationale, Review of Existing Data and Emerging Technologies.

PMID- 27048701
TI  - Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic
      Microembolism-Induced Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Microthrombi originating from disintegrated clots or
      formed in situ may account for the poor clinical improvement of acute ischemic
      stroke after recanalization therapy. We attempted to determine whether
      microbubble-mediated sonothrombolysis could dissolve platelet-rich and
      erythrocyte-rich microthrombi, thereby reducing their brain injury-causing
      potential. METHODS: Platelet- and erythrocyte-rich microthrombosis were induced
      by periadventitial application of 5% ferric chloride or thrombin to mesenteric
      microvessels in 75 Sprague-Dawley rats. Acute ischemic stroke was induced by
      intracarotid injection of platelet- or erythrocyte-rich microthrombi in another
      50 rats. Rats were randomly divided into control (CON), ultrasound (US),
      ultrasound and microbubble (US+MB), recombinant tissue-type plasminogen activator
      (r-tPA), and US+MB+r-tPA groups. The post-treatment mesenteric microvessel
      recanalization rates, cerebral infarct volumes, and neurological scores were
      determined. RESULTS: The recanalization rates of platelet- and erythrocyte-rich
      microthrombi in mesenteric microvessels were higher (P<0.05), and the cerebral
      infarct volumes and neurological scores of rats with either microthrombi were
      lower in the US+MB group than in the CON group (P<0.01). The infarct volumes and
      neurological scores were greater in the r-tPA group than in the US+MB and US+MB+r
      tPA groups after treatment of rats with platelet-rich microthrombi (P<0.05). In
      contrast, after treatment of rats with erythrocyte-rich microthrombi, the infarct
      volumes and neurological scores were similar in the r-tPA and US+MB groups, but
      smaller in the US+MB+r-tPA group (P<0.05). CONCLUSIONS: Microbubble-mediated
      sonothrombolysis improved the outcomes of microthrombi-induced acute ischemic
      stroke. Thus, this method may serve as an attractive adjunct to recanalization
      therapy for acute ischemic stroke.

PMID- 27048702
TI  - Geographic Localization: The Need for Better Reporting and Outcome Selection.

PMID- 27048703
TI  - Testing the Relationships between Diversification, Species Richness, and Trait
      Evolution.
AB  - Understanding which traits drive species diversification is essential for
      macroevolutionary studies and to understand patterns of species richness among
      clades. An important tool for testing if traits influence diversification is to
      estimate rates of net diversification for each clade, and then test for a
      relationship between traits and diversification rates among clades. However, this
      general approach has become very controversial. Numerous papers have now stated
      that it is inappropriate to analyze net diversification rates in groups in which
      clade richness is not positively correlated with clade age. Similarly, some have
      stated that variation in net diversification rates does not explain variation in
      species richness patterns among clades across the Tree of Life. Some authors have
      also suggested that strong correlations between richness and diversification
      rates are a statistical artifact and effectively inevitable. If this latter point
      is true, then correlations between richness and diversification rates would be
      uninformative (or even misleading) for identifying how much variation in species
      richness among clades is explained by variation in net diversification rates.
      Here, we use simulations (based on empirical data for plethodontid salamanders)
      to address three main questions. First, how is variation in net diversification
      rates among clades related to the relationship between clade age and species
      richness? Second, how accurate are these net diversification rate estimators, and
      does the age-richness relationship have any relevance to their accuracy? Third,
      is a relationship between species richness and diversification rates an
      inevitable, statistical artifact? Our simulations show that strong, positive age
      richness relationships arise when diversification rates are invariant among
      clades, whereas realistic variation in diversification rates among clades
      frequently disrupts this relationship. Thus, a significant age-richness
      relationship should not be a requirement for utilizing net diversification rates
      in macroevolutionary studies. Moreover, we find no difference in the accuracy of
      net diversification rate estimators between conditions in which there are strong,
      positive relationships between clade age and richness and conditions in which
      these strong relationships are absent. We find that net diversification rate
      estimators are reasonably accurate under many conditions (true and estimated
      rates are strongly corrrelated, and typically differ by ~10-20%), but become more
      accurate when clades are older and less accurate when using incorrect assumptions
      about extinction. We also find that significant relationships between richness
      and diversification rates fail to arise under many conditions, especially when
      there are faster rates in younger clades. Therefore, a significant relationship
      between richness and diversification rates is not inevitable. Given this latter
      result, we suggest that relationships between richness and diversification should
      be tested for when attempting to explain the causes of richness patterns, to
      avoid potential misinterpretations (e.g., high diversification rates associated
      with low-richness clades). Similarly, our results also provide some support for
      previous studies suggesting that variation in diversification rates might explain
      much of the variation in species richness among major clades, based on strong
      relationships between clade richness and diversification rates.

PMID- 27048704
TI  - Socio-Emotional Adaptation Theory: Charting the Emotional Process of Alzheimer's
      Disease.
AB  - Purpose of the Study: The emotional reactions to the progression of Mild
      Cognitive Impairment and Alzheimer's disease (MCI/AD) oftentimes present as
      cognitive or behavioral changes, leading to misguided interventions by Formal
      Support (paid health care providers). Despite a rich body of literature
      identifying cognitive and behavioral staging of MCI/AD, the emotional changes
      that accompany these diagnoses have been largely ignored. The objective of this
      study was to develop a model of the emotional aspects of MCI/AD. Design and
      Methods: One hour, semistructured interviews, with 14 patient-Informal Support
      Partner dyads (N = 28) interviewed concurrently; patients were in various stages
      of MCI/AD. An interdisciplinary team employed a grounded theory coding process to
      detect emotional characteristics of the participants with MCI/AD. Results:
      Emotional reactions were categorized into depression/sadness, apathy,
      concern/fear, anger/frustration, and acceptance. The emotions did not present
      linearly along the course of the disease and were instead entwined within a set
      of complex (positive/negative) interactions including: relationship with the
      Informal Support Partner (i.e., teamwork vs infantilization), relationship with
      the Formal Support (i.e., patient vs disengaged), coping (i.e., adaptive vs
      nonadaptive), and perceived control (i.e., internal vs external locus-of
      control). For example, a person with poor formal and informal support and
      external locus-of-control may become depressed, a condition that is known to
      negatively affect cognitive status. Implications: Understanding the emotional
      reactions of individuals diagnosed with MCI/AD will provide clinicians with
      information needed to develop treatments suited to current needs of the patient
      and provide Informal Support Partners insight into cognitive and physical changes
      associated with MCI/AD.

PMID- 27048706
TI  - Organizational Change Around an Older Workforce.
AB  - Purpose of the Study: Demographic, economic, political, and technological
      transformations-including an unprecedented older workforce-are challenging
      outdated human resource logics and practices. Rising numbers of retirement
      eligible Boomers portend a loss of talent, skills, and local knowledge. We
      investigate organizational responses to this challenge-institutional work
      disrupting age-graded mindsets and policies. Design and Methods: We focus on
      innovative U.S. organizations in the Minneapolis-St. Paul region in the state of
      Minnesota, a hub for businesses and nonprofits, conducting in-depth interviews
      with informants from a purposive sample of 23 for-profit, nonprofit, and
      government organizations. Results: Drawing on an organizational change
      theoretical approach, we find organizations are leading change by developing
      universal policies and practices, not ones intentionally geared to older workers.
      Both their narratives and strategies-opportunities for greater employee
      flexibility, training, and scaling back time commitments-suggest deliberate
      disrupting of established age-graded logics, replacing them with new logics
      valuing older workers and age-neutral approaches. Organizations in the different
      sectors studied are fashioning uniform policies regardless of age, exhibiting a
      parallel reluctance to delineate special policies for older workers.
      Implications: Developing new organizational logics and practices valuing,
      investing in, and retaining older workers is key 21st century business
      challenges. The flexibility, training, and alternative pathways offered by the
      innovative organizations we studied point to fruitful possibilities for large
      scale replacement of outdated age-biased templates of work, careers, and
      retirement.

PMID- 27048705
TI  - A Communication Intervention to Reduce Resistiveness in Dementia Care: A Cluster
      Randomized Controlled Trial.
AB  - Purpose of the Study: Nursing home (NH) residents with dementia exhibit
      challenging behaviors or resistiveness to care (RTC) that increase staff time,
      stress, and NH costs. RTC is linked to elderspeak communication. Communication
      training (Changing Talk [CHAT]) was provided to staff to reduce their use of
      elderspeak. We hypothesized that CHAT would improve staff communication and
      subsequently reduce RTC. Methods: Thirteen NHs were randomized to intervention
      and control groups. Dyads (n = 42) including 29 staff and 27 persons with
      dementia were videorecorded during care before and/or after the intervention and
      at a 3-month follow-up. Videos were behaviorally coded for (a) staff
      communication (normal, elderspeak, or silence) and (b) resident behaviors
      (cooperative or RTC). Linear mixed modeling was used to evaluate training
      effects. Results: On average, elderspeak declined from 34.6% (SD = 18.7) at
      baseline by 13.6% points (SD = 20.00) post intervention and 12.2% points (SD =
      22.0) at 3-month follow-up. RTC declined from 35.7% (SD = 23.2) by 15.3% points
      (SD = 32.4) post intervention and 13.4% points (SD = 33.7) at 3 months. Linear
      mixed modeling determined that change in elderspeak was predicted by the
      intervention (b = -12.20, p = .028) and baseline elderspeak (b = -0.65, p <
      .001), whereas RTC change was predicted by elderspeak change (b = 0.43, p <
      .001); baseline RTC (b = -0.58, p < .001); and covariates. Implications: A brief
      intervention can improve communication and reduce RTC, providing an effective
      nonpharmacological intervention to manage behavior and improve the quality of
      dementia care. No adverse events occurred.

PMID- 27048707
TI  - Challenges and Strategies for Hospice Caregivers: A Qualitative Analysis.
AB  - Purpose: Family caregivers of hospice patients are responsible for the day-to-day
      care of their loved ones during the final months of life. They are faced with
      numerous challenges. The purpose of this study was to understand the challenges
      and coping strategies used by hospice caregivers as they care for their family
      members. Design: This study is a secondary analysis of data from an attention
      control group in a large randomized controlled trial testing a cognitive
      behavioral intervention with hospice caregivers. Methods: Audiotaped interviews
      were coded with initial themes and combined into final categories of caregiving
      challenges and strategies for managing the hospice caregiving experience.
      Results: Caregivers shared narratives discussing challenges that included their
      frustrations with patient care issues, emotional challenges, frustrations with
      various health care systems, financial problems, and personal health concerns.
      They also discussed coping strategies involving patient care, self-care, and
      emotional support. The coping techniques were both problem and emotion based.
      Implications: There is a need for interventions that focus on strengthening both
      problem-based and emotional-based coping skills to improve the caregiving
      experience.

PMID- 27048708
TI  - Quality of Life for Dementia Caregiving Dyads: Effects of Incongruent Perceptions
      of Everyday Care and Values.
AB  - Purpose of the Study: This dyadic study investigated incongruence in care
      recipients' (CRs') and caregivers' (CGs') perceptions of (a) CRs' involvement in
      decision making and (b) how much CRs value social relations as predictors of
      subjective quality of life (QOL) of CRs with mild-to-moderate dementia and their
      primary family CGs. Design and Methods: A secondary analysis of cross-sectional,
      dyadic data from in-person interviews with 205 CRs with mild-to-moderate dementia
      and their primary family CGs Incongruence was operationalized in two ways:
      absolute difference and direction of difference. Paired t tests and multilevel
      modeling were used to analyze differences. Results: CGs reported CRs were
      significantly less involved in decision making and valued social relations
      significantly less than CRs. Greater incongruence on CRs' values significantly
      predicted lower QOL of CG and CR. When CGs reported that CRs valued social
      relationships less than the CR himself/herself reported, CGs' and CRs' QOL was
      significantly lower compared with QOL for dyads where there was no incongruence
      on CRs' values. Incongruent perceptions of CRs' involvement in decisions were not
      a significant predictor of QOL. Implications: This study provides evidence for
      the importance of assessing both CRs' and CGs' QOL, as well as incongruence in
      their perceptions in domains that may affect both of their QOL.

PMID- 27048709
TI  - Communicative Coping Behavior Checklist: Observation of Persons With Dementia in
      the Home Environment.
AB  - PURPOSE OF THE STUDY: Communication contributes to increased stress, mortality,
      and decreased quality of life (QOL) for persons with dementia (PWD) and
      caregivers. PWD use communicative coping behaviors (CCBs) to manage the demands
      of the disease. However, most assessments neither look for nor give credit to
      communication behaviors. This is the first study to examine CCBs in the home
      environment as measured by the Communicative Coping Behavior Checklist (CCBC).
      DESIGN AND METHODS: This cross-sectional quantitative study included 26 dementia
      and 18 cognitively normal control dyads. Raters observed their partners' CCBs at
      home, over several weeks and completed the CCBC. We analyzed the endorsement
      rates (how often behaviors were observed by a rater) of emotion and activity
      focused CCBs in dementia and control dyads. RESULTS: The primary outcome was rate
      of CCB endorsement. Secondary outcomes included dementia diagnosis, cognitive
      status, depressive mood, life satisfaction (SWL) and QOL. Dementia dyads endorsed
      11 of 23 CCBs significantly more than control dyads. Action-focused CCBs (p <
      .001) were more frequent than emotion-focused CCBs (p = .004) in dementia dyads.
      Specific CCBs such as humor correlated with higher caregiver QOL (p = .019) and
      PWD's SWL (p = .003). Another CCB, general humor, correlated with lower PWD's SWL
      (p = .024). IMPLICATIONS: This was the first study to examine CCBs in the home
      environment comparing dementia and control dyads. Higher endorsement rates of
      action-focused than emotion-focused CCBs were seen in dementia dyads. We conclude
      that attention to CCBs during treatment and care will improve QOL and SWL of PWD
      and caregivers.

PMID- 27048710
TI  - United States Indigenous Populations and Dementia: Is There a Case for Culture
      based Psychosocial Interventions?
AB  - Dementia is an issue of increasing importance in indigenous populations in the
      United States. We begin by discussing what is known about dementia prevalence and
      elder family caregiving in American Indian, Alaska Native, and Native Hawaiian
      populations. We briefly highlight examples of culture-based programming developed
      to address a number of chronic diseases and conditions that disproportionately
      affect these communities. These programs have produced positive health outcomes
      in American Indian, Alaska Native, and Native Hawaiian populations and may have
      implications for research and practice in the dementia context of culture-based
      interventions. Evidence-based and culture-based psychosocial programming in
      dementia care for indigenous populations in the United States designed by the
      communities they intend to serve may offer elders and families the best potential
      for care that is accessible, respectful, and utilized.

PMID- 27048711
TI  - Knockdown of retinoblastoma protein may sensitize glioma cells to cisplatin
      through inhibition of autophagy.
AB  - Glioblastoma multiforme (GBM) is one of the deadliest forms of cancer due to its
      limited sensitivity to chemotherapy and radiotherapy. Cisplatin (CCDP) is a
      widely used chemotherapeutic agent for tumors, but the agent often results in the
      development of chemo-resistance. In several cancers, cisplatin resistance is
      associated with autophagy induction. Here, we found that in glioma cells
      cisplatin treatment induced autophagy. Our data indicates that the autophagy
      induction plays a critical role in cisplatin resistance of glioma cells,
      knockdown of RB inhibited autophagy induced by cisplatin, and inhibition of
      autophagy improved cisplatin-induced apoptosis. It suggests that a combination of
      autophagy inhibitors with cisplatin may improve the therapeutic efficiency of
      cisplatin towards GBM with acquired resistance.

PMID- 27048712
TI  - Orexin neurons in the lateral hypothalamus project to the medial prefrontal
      cortex with a rostro-caudal gradient.
AB  - Orexin neurons in the lateral hypothalamus (LH) play an important role in
      arousal, guaranteeing the execution of medial prefrontal cortex (mPFC)-related
      higher cognitive functions. The mPFC is anatomically and functionally a rostro
      caudal hierarchy. Little is known about the innervation pattern, especially in
      the rostro-caudal model, from the arousal-promoting orexin system in the LH to
      the mPFC subregions, including the anterior cingulate cortex (AC), prelimbic
      cortex (PL) and infralimbic cortex (IL). Here, we used an anterograde tracing
      method and immunohistochemistry and found that the density of the LH, as well as
      orexinergic, fibers increased from the rostral part to the caudal part of the
      mPFC, regardless of AC, PL or IL. Similarly, the distribution of type 1 orexin
      receptors in the mPFC follows a rostro-caudal increasing gradient hierarchy.
      These data suggest a rostro-caudal hierarchy of LH orexinergic innervation to the
      mPFC. We hope to provide anatomical and morphological evidence for the regulation
      pattern of the arousal-promoting orexin system on the cognition-related mPFC
      system.

PMID- 27048713
TI  - On hybrid circuits exploiting thermistive properties of slime mould.
AB  - Slime mould Physarum polycephalum is a single cell visible by the unaided eye.
      Let the slime mould span two electrodes with a single protoplasmic tube: if the
      tube is heated to approximately ~40  degrees C, the electrical resistance of the
      protoplasmic tube increases from ~3 MOmega to ~10,000 MOmega. The organism's
      resistance is not proportional nor correlated to the temperature of its
      environment. Slime mould can therefore not be considered as a thermistor but
      rather as a thermic switch. We employ the P. polycephalum thermic switch to
      prototype hybrid electrical analog summator, NAND gates, and cascade the gates
      into Flip-Flop latch. Computing operations performed on this bio-hybrid computing
      circuitry feature high repeatability, reproducibility and comparably low
      propagation delays. 

PMID- 27048714
TI  - Predictors of blood pressure at 7-13 years: The "new millennium baby" study.
AB  - BACKGROUND AND AIMS: The purpose of this study is to evaluate the association
      between blood pressure (BP) at 7-13 years of age and body mass index (BMI), early
      feeding, lifestyle indicators, and parental characteristics. METHODS AND RESULTS:
      Retrospective plus cross-sectional cohort study was started in 1294 children born
      in 2000-2004, right from their birth in primary care settings. Early feeding was
      estimated by measuring breast-feeding (BF) duration, complementary feeding (CF)
      introduction time, and lifestyle indicators such as daily screen time and weekly
      extracurricular sports activity time. Parental education, smoking, and obesity
      related diseases were also considered. Multivariable linear regression and
      mediation analysis were used. CF introduction at 5-6 months of age was a negative
      predictor of systolic and diastolic BP (mean systolic BP-standard deviation score
      (SDS) -0.38 [95% CI: -0.47, -0.29] (p < 0.001); mean diastolic BP-SDS -0.32 [95%
      CI: -0.40, -0.24]) (p < 0.001); BMI was a positive predictor of systolic and
      diastolic BP (p < 0.001); and parental hypertension was a positive predictor of
      diastolic BP (p < 0.05). Predictors of mean BMI-SDS at 7-13 years of age were
      birth weight, screen time, and parental obesity and smoking (p < 0.001). BF had
      no effect on BP or BMI. Mediation analysis showed virtually no indication of the
      effect of CF on BP mediated by BMI. CONCLUSIONS: CF introduction between 5 and 6
      months of age could be associated with low BP at 7-13 years. The effect of CF on
      BP seems to be independent of BMI. Low screen time is associated with low BMI. CF
      time may play a role in the occurrence of surrogates of noncommunicable disorders
      in future.

PMID- 27048715
TI  - White blood cell count may identify abnormal cardiometabolic phenotype and
      preclinical organ damage in overweight/obese children.
AB  - BACKGROUND AND AIMS: Subclinical inflammation is a central component of
      cardiometabolic disease risk in obese subjects. The aim of the study was to
      evaluate whether the white blood cell count (WBCc) may help to identify an
      abnormal cardiometabolic phenotype in overweight (Ow) or obese (Ob) children.
      METHODS AND RESULTS: A cross-sectional sample of 2835 Ow/Ob children and
      adolescents (age 6-18 years) was recruited from 10 Italian centers for the care
      of obesity. Anthropometric and biochemical variables were assessed in the overall
      sample. Waist to height ratio (WhtR), alanine aminotransferase (ALT), lipids, 2 h
      post-load plasma glucose (2hPG), left ventricular (LV) geometry and carotid
      intima-media thickness (cIMT) were assessed in 2128, 2300, 1834, 535 and 315
      children, respectively. Insulin resistance and whole body insulin sensitivity
      index (WBISI) were analyzed using homeostatic model assessment (HOMA-IR) and
      Matsuda's test. Groups divided in quartiles of WBCc significantly differed for
      body mass index, WhtR, 2hPG, HOMA-IR, WBISI, lipids, ALT, cIMT, LV mass and
      relative wall thickness. Children with high WBCc (>=8700 cell/mm(3)) showed a 1.3
      2.5 fold increased probability of having high normal 2hPG, high ALT, high cIMT,
      or LV remodeling/concentric LV hypertrophy, after adjustment for age, gender,
      pubertal status, BMI and centers. CONCLUSIONS: This study shows that WBCc is
      associated with early derangements of glucose metabolism and preclinical signs of
      liver, vascular and cardiac damage. The WBCc may be an effective and low-cost
      tool for identifying Ow and Ob children at the greatest risk of potential
      complications.

PMID- 27048716
TI  - Association between serum adiponectin levels and muscular fitness in Portuguese
      adolescents: LabMed Physical Activity Study.
AB  - BACKGROUND AND AIM: Paradoxically, recent investigations have showed that
      adiponectin levels are inversely associated with muscle strength. However, to
      date, there is a lack of knowledge on the relationship between muscular fitness
      (MF) and adiponectin levels in adolescents. We aimed to examine the independent
      associations between MF and adiponectin levels in adolescents, controlling for
      several potential confounders. METHODS AND RESULTS: This is a cross-sectional
      analysis with 529 Portuguese adolescents aged 12-18 years. A MF score was
      computed as the mean of the handgrip strength and standing long jump standardized
      values by age and gender. We measured fasting glucose, insulin, HDL-cholesterol,
      C-reactive protein and adiponectin. Linear regression analysis showed a
      significant inverse association between adiponectin (Z-score by age and sex) and
      MF score, after adjustments for age, sex, pubertal stage, socioeconomic status,
      adherence to the Mediterranean diet, body mass index, HOMA-IR, HDL-cholesterol, C
      reactive protein and cardiorespiratory fitness (unstandardized beta = -0.176; p <
      0.005). Analysis of covariance showed a significant difference between the Low
      MF/Non-overweight group and the High MF/Non-overweight Group (p < 0.05) and
      between the Low MF/Non-overweight and High MF/Overweight Group (p < 0.05) (F (5,
      523) = 2.262, p = 0.047). CONCLUSION: Adiponectin circulating levels are
      inversely and independently associated with MF. In non-overweight adolescents,
      those with high levels of MF presented lower levels of adiponectin compared to
      those with Low MF. Likewise, overweight adolescents with High MF presented lower
      levels of serum adiponectin than non-overweight adolescents with Low MF.

PMID- 27048717
TI  - The development and use of a crystallographic database.
AB  - To scientists working with small-molecule or organometallic compounds, the
      Cambridge Structural Database constitutes an extremely important tool for
      reference to individual crystal structures and as a data source for statistical
      investigations. The article by Groom et al. [(2016), Acta Cryst. B72, 171-179]
      provides updated information on the use, development and future of this database.

PMID- 27048718
TI  - Expanding the usage of the Source Function to experimental electron densities.
AB  - The Source Function provides unique information about chemical bonding in the
      solid state, from theory as well as from experiment. It is now established that
      the concept of electronic delocalization in aromatic systems can be accurately
      studied using X-ray derived electron densities, and even more importantly the
      contributions are transferable between similar systems. 

PMID- 27048719
TI  - The Cambridge Structural Database.
AB  - The Cambridge Structural Database (CSD) contains a complete record of all
      published organic and metal-organic small-molecule crystal structures. The
      database has been in operation for over 50 years and continues to be the primary
      means of sharing structural chemistry data and knowledge across disciplines. As
      well as structures that are made public to support scientific articles, it
      includes many structures published directly as CSD Communications. All structures
      are processed both computationally and by expert structural chemistry editors
      prior to entering the database. A key component of this processing is the
      reliable association of the chemical identity of the structure studied with the
      experimental data. This important step helps ensure that data is widely
      discoverable and readily reusable. Content is further enriched through selective
      inclusion of additional experimental data. Entries are available to anyone
      through free CSD community web services. Linking services developed and
      maintained by the CCDC, combined with the use of standard identifiers, facilitate
      discovery from other resources. Data can also be accessed through CCDC and third
      party software applications and through an application programming interface. 

PMID- 27048720
TI  - Source Function applied to experimental densities reveals subtle electron
      delocalization effects and appraises their transferability properties in
      crystals.
AB  - The Source Function (SF), introduced in 1998 by Richard Bader and Carlo Gatti, is
      succinctly reviewed and a number of paradigmatic applications to in vacuo and
      crystal systems are illustrated to exemplify how the SF may be used to discuss
      chemical bonding in both conventional and highly challenging cases. The SF
      enables the electron density to be seen at a point determined by source
      contributions from the atoms or a group of atoms of a system, and it is therefore
      well linked to the chemist's awareness that any local property and chemical
      behaviour is to some degree influenced by all the remaining parts of a system.
      The key and captivating feature of the SF is that its evaluation requires only
      knowledge of the electron density (ED) of a system, thereby enabling a comparison
      of ab initio and X-ray diffraction derived electron density properties on a
      common and rigorous basis. The capability of the SF to detect electron
      delocalization effects and to quantify their degree of transferability is
      systematically explored in this paper through the analysis and comparison of
      experimentally X-ray derived Source Function patterns in benzene, naphthalene and
      (+/-)-8'-benzhydrylideneamino-1,1'-binaphthyl-2-ol (BAB) molecular crystals. It
      is shown that the SF tool recovers the characteristic SF percentage patterns
      caused by pi-electron conjugation in the first two paradigmatic aromatic
      molecules in almost perfect quantitative agreement with those obtained from ab
      initio periodic calculations. Moreover, the effect of chemical substitution on
      the degree of transferability of such patterns to the benzene- and naphthalene
      like moieties of BAB is neatly shown and quantified by the observed systematic
      deviations, relative to benzene and naphthalene, of only those SF contributions
      from the substituted C atoms. Finally, the capability of the SF to reveal
      electron-delocalization effects is challenged by using a promolecule density,
      rather than the proper quantum mechanical density, to determine the changes in SF
      patterns along the cyclohexene, 1,3-cyclohexadiene and benzene molecule series.
      It is shown that, differently from the proper quantum density, the promolecular
      density is unable to reproduce the SF trends anticipated by the increase of
      electron delocalization along the series, therefore ruling out the geometrical
      effect as being the only cause for the observed SF patterns changes. 

PMID- 27048721
TI  - Structure modulations in nonlinear optical (NLO) materials Cs(2)TB4O9 (T = Ge,
      Si).
AB  - Incommensurately modulated borate structures of a new type were studied in detail
      in the nonlinear optical (NLO) materials Cs(2)TB4O9 (T = Ge, Si) using single
      crystal X-ray diffraction techniques. The structures were solved by the charge
      flipping algorithm in the superspace group I2(alphabeta0)0. The refinement
      results strongly suggest that the main structure modulation feature of Cs(2)TB4O9
      is the ordering of the O atoms. With these modulated structure models, the
      unreasonable B-O distances in the average structures were explained as the
      ordering of BO4 and BO3.

PMID- 27048722
TI  - A novel polytype - the stacking fault based gamma-MoO3 nanobelts.
AB  - gamma-MoO3 nanobelts prepared by hydrothermal synthesis were studied by
      synchrotron radiation powder diffraction, scanning electron microscopy,
      transmission electron microscopy and selected area electron diffraction. Their nm
      dimensions, in particular in two crystallographic directions, have a profound
      influence on electrochemical properties during cycling as the cathode material in
      lithium-ion batteries (LIBs). The diffraction analysis shows clearly that the
      crystal structure for the gamma-MoO3 nanobelts differs significantly from that of
      bulk alpha-MoO3. The observed powder diffraction pattern, with asymmetric peaks,
      extremely broad peaks, as well as additional or absent diffraction peaks, is
      fully described by means of a model based on stacking disorder of MoO3 slabs. 

PMID- 27048723
TI  - Melilite-like modulation and temperature-dependent evolution in the framework
      structure of K2Sc[Si2O6]F.
AB  - The crystal structure of synthetic K2Sc[Si2O6]F has been solved and refined as an
      incommensurately modulated structure in (3 + 2)-dimensional superspace. This
      paper describes the tetragonal structure in the superspace group
      P42/mnm(alpha,alpha,0)000s(-alpha,alpha,0)0000 [a = 8.9878 (1), c = 8.2694 (2) A,
      V = 668.01 (2) A(3)] with modulation wavevectors q1 = 0.2982 (4)(a* + b*) and q2
      = 0.2982 (4)(-a* + b*). Structure refinement taking into account the modulation
      of positional and ADP parameters for all atoms from 3074 observed main hkl00 and
      satellite reflections hklmn of first order with single, m.n = 0, and mixed, m.n =
      +/-1, indices converged to a final R value of 0.0514. The structure is a mixed
      octahedral-tetrahedral framework composed of [ScO4F2] octahedra, [Si4O12] rings
      and K in variable coordination. Due to the modulation the O atoms move into and
      out of the first coordination sphere of K leading to a minimum of five and a
      maximum of 10 interatomic K-O distances up to 3.1 A. Although this feature is
      comparable to observations in modulated fresnoite and melilite group compounds,
      these structures differ from K2Sc[Si2O6]F with respect to their topology. On
      temperature increase the intensity of the satellite reflections decreases until
      they disappear just above 443 K. The high-temperature normal structure, in space
      group P42/mnm, is identical to the room-temperature average structure of
      K2Sc[Si2O6]F. 

PMID- 27048724
TI  - An exceptional 5:4 enantiomeric structure.
AB  - The only crystals that could be grown from racemic solutions of the PF6(-) salt
      of the resolvable cation [Ru(2,9-dimethyl-1,10-phenanthroline)2(dipyrido[3,2
      d:2',3'-f]quinoxaline)](2+) have translational symmetry only (space group P1),
      contain nine independent sets of ions, and include numerous independent solvent
      molecules (11 acetone, one diethyl ether and possibly several water molecules).
      Layers of hydrophobic cations alternate with layers containing most of the anions
      and solvent molecules. All nine cations have the same basic conformation, which
      is distorted by the presence of the methyl substituents on the two 1,10
      phenanthroline ligands. Four pairs of enantiomeric cations within a layer are
      related by approximate inversion centers; the ninth cation, which shows no sign
      of disorder, makes the layer chiral. Within the cation layers stripes parallel to
      [110] of six cations alternate with stripes of three; the local symmetry and the
      cation orientations are different in the two stripes. These stripes are reflected
      in the organization of the anion/solvent layer. The ca 80:20 inversion twinning
      found indicates that enantiomeric preference is transmitted less perfectly across
      the anion/solvent layer than within the cation layer. The structure is
      exceptional in having nine independent formula units and an unbalanced set (ratio
      4:5) of resolvable enantiomers. The difficulty in growing crystals of this
      material is consistent with its structural complexity. 

PMID- 27048725
TI  - Molecular structure of diethylaminoalane in the solid state: an X-ray powder
      diffraction, DFT calculation and Raman spectroscopy study.
AB  - The crystal structure of diethylaminoalane, [H2Al-N(C2H5)2]2, was determined by X
      ray powder diffraction in conjunction with DFT calculations. Diethylaminoalane
      crystallizes in the monoclinic space group P21/c with a = 7.4020 (2), b = 12.9663
      (3), c = 7.2878 (2) A and beta = 90.660 (2) degrees  at 293 K. The crystal
      structure was confirmed by DFT calculations and Raman spectroscopy. The molecular
      structure of diethylaminoalane consists of dimers of [H2Al-N(CH2CH3)2] in which
      an Al2N2 four-membered ring is formed by a center of inversion. Such an
      arrangement of the aminoalane moieties in the crystal structure is well known for
      this class of compound, as shown by the comparison with ethylmethylaminoalane and
      diisopropylaminoalane. 

PMID- 27048726
TI  - Geometry of trigonal boron coordination sphere in boronic acids derivatives - a
      bond-valence vector model approach.
AB  - The systematic analysis of the geometry of three-coordinate boron in boronic acid
      derivatives with a common [CBO2] skeleton is presented. The study is based on the
      bond-valence vector (BVV) model [Zachara (2007). Inorg. Chem. 46, 9760-9767], a
      simple tool for the identification and quantitative estimation of both steric and
      electronic factors causing deformations of the coordination sphere. The empirical
      bond-valence (BV) parameters in the exponential equation [Brown & Altermatt
      (1985). Acta Cryst. B41, 244-247] rij and b, for B-O and B-C bonds were
      determined using data deposited in the Cambridge Structural Database. The values
      obtained amount to rBO = 1.364 A, bBO = 0.37 A, rBC = 1.569 A, bBC = 0.28 A, and
      they were further used in the calculation of BVV lengths. The values of the
      resultant BVV were less than 0.10 v.u. for 95% of the set comprising 897 [CBO2]
      fragments. Analysis of the distribution of BVV components allowed for the
      description of subtle in- and out-of plane deviations from the 'ideal' (sp(2))
      geometry of boron coordination sphere. The distortions specific for distinct
      groups of compounds such as boronic acids, cyclic and acyclic esters,
      benzoxaboroles and hemiesters were revealed. In cyclic esters the direction of
      strains was found to be controlled by the ring size effect. It was shown that the
      syn or anti location of substituents on O atoms is decisive for the deformations
      direction for both acids and acyclic esters. The greatest strains were observed
      in the case of benzoxaboroles which showed the highest deviation from the zero
      value of the resultant BVV. The out-of-plane distortions, described by the vz
      component of the resultant BVV, were ascertained to be useful in the
      identification of weak secondary interactions on the fourth coordination site of
      the boron centre. 

PMID- 27048727
TI  - Quartz: structural and thermodynamic analyses across the alpha <-> beta
      transition with origin of negative thermal expansion (NTE) in beta quartz and
      calcite.
AB  - The temperature variation, T, of the crystal structure of quartz, SiO2, from 298
      to 1235 K was obtained with synchrotron powder X-ray diffraction data and
      Rietveld structure refinements. The polymorphic transformation from P3221 (low-T,
      alpha quartz) to P6222 (high-T, beta quartz) occurs at a transition temperature,
      Ttr = 847 K. The T variations of spontaneous strains and several structural
      parameters are fitted to an order parameter, Q, using Landau theory. The change
      in Si atom coordinate, Six, gives Ttr - Tc = 0.49 K, which indicates an alpha <->
      beta transition that is weakly first order and nearly tricritical in character
      (Q(4) ? T). Strains give higher Ttr - Tc values (? 7 K). Other fitted parameters
      are the oxygen Oz coordinate, Si-Si distance, Si-O-Si and phi angles, and
      intensity of the (111) reflection, I111. In alpha quartz, the Si-Si distance
      increases with T because of cation repulsion, so the Si-O-Si angle increases (and
      phi decreases) and causes the thermal expansion of the framework structure that
      consists of corner-sharing distorted rigid SiO4 tetrahedra. The Si-Si distances
      contract with T and cause negative thermal expansion (NTE) in beta quartz because
      of increasing thermal librations of the O atom in the Si-O-Si linkage that occur
      nearly perpendicular to the Si-Si contraction. In calcite, CaCO3, the short Ca-Ca
      distance expands with T, but the next-nearest Ca-Ca distance, which is of equal
      length to the a axis, contracts with T and causes NTE along the a axis. The
      thermal librations of the atoms in the rigid CO3 group increase with T along the
      c axis. 

PMID- 27048728
TI  - New polymorphs of an old drug: conformational and synthon polymorphism of 5
      nitrofurazone.
AB  - Two new polymorphic forms of 5-nitrofurazone (5-nitro-2-furaldehyde
      semicarbazone) have been synthesized and structurally characterized by single
      crystal and powder X-ray diffraction methods, vibrational spectroscopy (FT-IR and
      temperature Raman), differential scanning calorimetry (DSC), thermogravimetric
      analysis (TGA) and Hirshfeld surface analysis. The compound crystallizes in three
      different polymorphic forms P21/a (polymorph alpha), P21 (polymorph beta) and
      P21/c (polymorph gamma), the crystal structures of two of which (polymorphs beta
      and gamma) represent new structure determinations. The solid-state molecular
      organization in the three crystal forms is analyzed and discussed in terms of
      molecular conformation, crystal packing and hydrogen-bonded networks. All three
      crystals are formed from trans geometrical isomers, but the molecular
      conformation of the alpha-polymorph is syn-anti-anti-anti, while that of beta-
      and gamma-polymorphs is syn-anti-syn-syn. As a consequence of this the hydrogen
      bond donor and acceptor sites of the molecules are oriented differently, which in
      turn results in different hydrogen-bond connectivity and packing patterns. 

PMID- 27048729
TI  - Structural complexity and configurational entropy of crystals.
AB  - Using a statistical approach, it is demonstrated that the complexity of a crystal
      structure measured as the Shannon information per atom [Krivovichev (2012). Acta
      Cryst. A68, 393-398] represents a negative contribution to the configurational
      entropy of a crystalline solid. This conclusion is in full accordance with the
      general agreement that information and entropy are reciprocal variables. It also
      agrees well with the understanding that complex structures possess lower
      entropies relative to their simpler counterparts. The obtained equation is
      consistent with the Landauer principle and points out that the information
      encoded in a crystal structure has a physical nature. 

PMID- 27048730
TI  - Resolving the structure of TiBe12.
AB  - There has been considerable controversy regarding the structure of TiBe12, which
      is variously reported as hexagonal and tetragonal. Lattice dynamics simulations
      based on density functional theory (DFT) show the tetragonal phase space group
      I4/mmm to be more stable over all temperatures, while the hexagonal phase
      exhibits an imaginary phonon mode, which, if followed, would lead to the cell
      adopting the tetragonal structure. We then report the predicted ground state
      elastic constants and temperature dependence of the bulk modulus and thermal
      expansion for the tetragonal phase. 

PMID- 27048735
TI  - Longitudinal prediction of language emergence in infants at high and low risk for
      autism spectrum disorder.
AB  - This study used a prospective longitudinal design to examine the early
      developmental pathways that underlie language growth in infants at high risk (n =
      50) and low risk (n = 34) for autism spectrum disorder in the first 18 months of
      life. While motor imitation and responding to joint attention (RJA) have both
      been found to predict expressive language in children with autism spectrum
      disorder and those with typical development, the longitudinal relation between
      these capacities has not yet been identified. As hypothesized, results revealed
      that 15-month RJA mediated the association between 12-month motor imitation and
      18-month expressive vocabulary, even after controlling for earlier levels of RJA
      and vocabulary. These results provide new information about the developmental
      sequencing of skills relevant to language growth that may inform future
      intervention efforts for children at risk for language delay or other
      developmental challenges.

PMID- 27048737
TI  - A nanoporous polymer film as a diffuser as well as a light extraction component
      for top emitting organic light emitting diodes with a strong microcavity
      structure.
AB  - To improve the viewing angle characteristic as well as the light extraction
      effect of strong microcavity devices, we fabricated a nanoporous polymer film
      (NPF) as a scattering medium as well as a light extraction component. We designed
      two types of organic light emitting diodes (OLEDs) with a strong microcavity
      effect by changing the thickness of the hole transport layer (HTL; e.g., 30 nm
      and 60 nm) to investigate two different scattering effects of the NPF. Very
      interestingly, we could observe a significant enhancement of the external quantum
      efficiency (EQE) for each device (30 nm thick HTL: 18.0%, 60 nm thick HTL: 31.6%)
      when we attached a NPF formed on a 125 MUm thick PET film coated with the NPF.
      Furthermore, the NPF successfully suppressed the viewing angle dependence to
      realize ideal angular emission even in the two extreme microcavity conditions
      although they are still different from that of a Lambertian distribution.

PMID- 27048738
TI  - 2- and 6-O-sulfated proteoglycans have distinct and complementary roles in
      cranial axon guidance and motor neuron migration.
AB  - The correct migration and axon extension of neurons in the developing nervous
      system is essential for the appropriate wiring and function of neural networks.
      Here, we report that O-sulfotransferases, a class of enzymes that modify heparan
      sulfate proteoglycans (HSPGs), are essential to regulate neuronal migration and
      axon development. We show that the 6-O-sulfotransferases HS6ST1 and HS6ST2 are
      essential for cranial axon patterning, whilst the 2-O-sulfotransferase HS2ST
      (also known as HS2ST1) is important to regulate the migration of facial
      branchiomotor (FBM) neurons in the hindbrain. We have also investigated how HS2ST
      interacts with other signals in the hindbrain and show that fibroblast growth
      factor (FGF) signalling regulates FBM neuron migration in an HS2ST-dependent
      manner.

PMID- 27048739
TI  - Identification of a regulatory domain controlling the Nppa-Nppb gene cluster
      during heart development and stress.
AB  - The paralogous genes Nppa and Nppb are organized in an evolutionarily conserved
      cluster and provide a valuable model for studying co-regulation and regulatory
      landscape organization during heart development and disease. Here, we analyzed
      the chromatin conformation, epigenetic status and enhancer potential of sequences
      of the Nppa-Nppb cluster in vivo Our data indicate that the regulatory landscape
      of the cluster is present within a 60-kb domain centered around Nppb Both
      promoters and several potential regulatory elements interact with each other in a
      similar manner in different tissues and developmental stages. The distribution of
      H3K27ac and the association of Pol2 across the locus changed during cardiac
      hypertrophy, revealing their potential involvement in stress-mediated gene
      regulation. Functional analysis of double-reporter transgenic mice revealed that
      Nppa and Nppb share developmental, but not stress-response, enhancers,
      responsible for their co-regulation. Moreover, the Nppb promoter was required,
      but not sufficient, for hypertrophy-induced Nppa expression. In summary, the
      developmental regulation and stress response of the Nppa-Nppb cluster involve the
      concerted action of multiple enhancers and epigenetic changes distributed across
      a structurally rigid regulatory domain.

PMID- 27048740
TI  - First identification of NDM-5 associated with OXA-181 in Escherichia coli from
      Egypt.

PMID- 27048741
TI  - Fecal bacterial microbiome diversity in chronic HIV-infected patients in China.
AB  - The purpose of this study was to identify fecal bacterial microbiome changes in
      patients with chronic human immunodeficiency virus (HIV) infection in China.
      Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and
      clustered into operational taxonomic units using the QIIME software. Relative
      abundance at the phylum and genus levels were calculated. Alpha diversity was
      determined by Chao 1 and observed-species indices, and beta diversity was
      determined by double principal component analysis using the estimated phylogeny
      based unweighted Unifrac distance matrices. Fecal samples of the patients with
      chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes
      (47.20% +/- 0.43 relative abundance) and Proteobacteria (37.21% +/- 0.36)
      compared with those of the non-HIV infected controls (17.95% +/- 0.06 and 3.81%
      +/- 0.02, respectively). Members of the genus Bilophila were exclusively detected
      in samples of the non-HIV infected controls. Bacteroides and arabacteroides were
      more abundant in the chronic HIV-infected patients. Our study indicated that
      chronic HIV-infected patients in China have a fecal bacterial microbiome
      composition that is largely different from that found in non-HIV infected
      controls, and further study is needed to evaluate whether microbiome changes play
      a role in disease complications in the distal gut, including opportunistic
      infections.

PMID- 27048742
TI  - DNA immunization as a technology platform for monoclonal antibody induction.
AB  - To combat the threat of many emerging infectious diseases, DNA immunization
      offers a unique and powerful approach to the production of high-quality
      monoclonal antibodies (mAbs) against various pathogens. Compared with traditional
      protein-based immunization approaches, DNA immunization is efficient for testing
      novel immunogen designs, does not require the production or purification of
      proteins from a pathogen or the use of recombinant protein technology and is
      effective at generating mAbs against conformation-sensitive targets. Although
      significant progress in the use of DNA immunization to generate mAbs has been
      made over the last two decades, the literature does not contain an updated
      summary of this experience. The current review provides a comprehensive analysis
      of the literature, including our own work, describing the use of DNA immunization
      to produce highly functional mAbs, in particular, those against emerging
      infectious diseases. Critical factors such as immunogen design, delivery
      approach, immunization schedule, use of immune modulators and the role of final
      boost immunization are discussed in detail. 

PMID- 27048743
TI  - Reply to Leenders.

PMID- 27048744
TI  - Prevention of Surgical Site Infections: Universal Decontamination Not for All,
      but for a Selection of Surgical Patients.

PMID- 27048745
TI  - Zika Virus: Implications for Public Health.
AB  - The World Health Organization has declared the current Zika virus (ZIKV) epidemic
      a public health emergency of international concern. Lack of vaccines and reliable
      diagnostic tests, broad geographical distribution of mosquito species that can
      transmit the virus, and absence of population immunity in newly affected
      countries are causes for concern. Although most infected persons are
      asymptomatic, ZIKV has been associated with a rise in cases of neurological
      complications and fetal central nervous system malformations. This defines such
      an arbovirus as something whose transmission should be prevented. This review
      summarizes the current understanding of ZIKV biology and epidemiology, as well as
      possible interventions to prevent contagion and transmission.

PMID- 27048746
TI  - Sexual Transmission of Zika Virus: Implications for Clinical Care and Public
      Health Policy.

PMID- 27048749
TI  - Seo YB et al (Clin Infect Dis 2016; 62:755-60).

PMID- 27048748
TI  - Association Between Initial Route of Fluoroquinolone Administration and Outcomes
      in Patients Hospitalized for Community-acquired Pneumonia.
AB  - BACKGROUND: Fluoroquinolones have equivalent oral and intravenous
      bioavailability, but hospitalized patients with community-acquired pneumonia
      (CAP) generally are treated intravenously. Our objectives were to compare
      outcomes of hospitalized CAP patients initially receiving intravenous vs oral
      respiratory fluoroquinolones. METHODS: This was a retrospective cohort study
      utilizing data from 340 hospitals involving CAP patients admitted to a non
      intensive care unit (ICU) setting from 2007 to 2010, who received intravenous or
      oral levofloxacin or moxifloxacin. The primary outcome was in-hospital mortality.
      Secondary outcomes included clinical deterioration (transfer to ICU, initiation
      of vasopressors, or invasive mechanical ventilation [IMV] initiated after the
      second hospital day), antibiotic escalation, length of stay (LOS), and cost.
      RESULTS: Of 36 405 patients who met inclusion criteria, 34 200 (94%) initially
      received intravenous treatment and 2205 (6%) received oral treatment. Patients
      who received oral fluoroquinolones had lower unadjusted mortality (1.4% vs 2.5%;
      P = .002), and shorter mean LOS (5.0 vs 5.3; P < .001). Multivariable models
      using stabilized inverse propensity treatment weighting revealed lower rates of
      antibiotic escalation for oral vs intravenous therapy (odds ratio [OR], 0.84; 95%
      confidence interval [CI], .74-.96) but no differences in hospital mortality (OR,
      0.82; 95% CI, .58-1.15), LOS (difference in days 0.03; 95% CI, -.09-.15), cost
      (difference in $-7.7; 95% CI, -197.4-182.0), late ICU admission (OR, 1.04; 95%
      CI, .80-1.36), late IMV (OR, 1.17; 95% CI, .87-1.56), or late vasopressor use
      (OR, 0.94; 95% CI, .68-1.30). CONCLUSIONS: Among hospitalized patients who
      received fluoroquinolones for CAP, there was no association between initial route
      of administration and outcomes. More patients may be treated orally without
      worsening outcomes.

PMID- 27048751
TI  - Assessing the potential to combine attitude tracking and health campaign
      evaluation surveys.
AB  - Issue addressed: Online surveys are becoming increasingly popular in health
      research because of the low cost and fast completion time. A large proportion of
      online survey costs are allocated to setup and administration expenses, which
      suggests that conducting fewer, longer surveys would be a cost-effective
      approach. The current study assessed whether the incorporation of a health
      campaign evaluation survey within a longitudinal attitudes and behaviours
      tracking survey produced different outcomes compared with the separate
      administration of the evaluation survey.Methods: Data were collected via an
      online panel, with 688 respondents completing the combined survey and 657
      respondents completing the evaluation-only survey. Regression analyses were
      conducted to examine whether survey type was related to the campaign evaluation
      results.Results: Those who completed the combined survey perceived the campaign
      advertisement to be more personally relevant than those completing the evaluation
      only survey. There were no differences in results relating to campaign awareness
      and reported behavioural change as a result of campaign exposure.Conclusions:
      There were minimal differences between results obtained from combining an
      attitude/behaviour tracking survey with a campaign evaluation survey. Any priming
      or order effects were limited to respondents' cognitive responses to the
      advertisement.So what?: The results suggest that health practitioners with
      limited resources available for tracking and evaluation research may be able to
      maximise outcomes by administering fewer, longer surveys.

PMID- 27048750
TI  - RNA Sequencing Quantification of Xenobiotic-Processing Genes in Various Sections
      of the Intestine in Comparison to the Liver of Male Mice.
AB  - Previous reports on tissue distribution of xenobiotic-processing genes (XPGs)
      have limitations, because many non-cytochrome P450 phase I enzymes have not been
      investigated, and one cannot compare the real mRNA abundance of multiple XPGs
      using conventional quantification methods. Therefore, this study aimed to
      quantify and compare the mRNA abundance of all major XPGs in the liver and
      intestine using RNA sequencing. The mRNA profiles of 304 XPGs, including phase I,
      phase II enzymes, phase II cosubstrate synthetic enzymes, xenobiotic
      transporters, as well as xenobiotic-related transcription factors, were
      systematically examined in the liver and various sections of the intestine in
      adult male C57BL/6J mice. By two-way hierarchical clustering, over 80% of the
      XPGs had tissue-divergent expression, which partitioned into liver-predominant,
      small intestine-predominant, and large intestine-predominant patterns. Among the
      genes, 54% were expressed highest in the liver, 21% in the duodenum, 4% in the
      jejunum, 6% in the ileum, and 15% in the large intestine. The highest-expressed
      XPG in the liver was Mgst1; in the duodenum, Cyp3a11; in the jejunum and ileum,
      Ces2e; and in the large intestine, Cyp2c55. Interestingly, XPGs in the same
      family usually exhibited highly different tissue distribution patterns, and many
      XPGs were almost exclusively expressed in one tissue and minimally expressed in
      others. In conclusion, the present study is among the first and the most
      comprehensive investigations of the real mRNA abundance and tissue-divergent
      expression of all major XPGs in mouse liver and intestine, which aids in
      understanding the tissue-specific biotransformation and toxicity of drugs and
      other xenobiotics.

PMID- 27048752
TI  - Electrophysiological evidence showing muscarinic agonist-antagonist activities of
      N-desmethylclozapine using hippocampal excitatory and inhibitory neurons.
AB  - The atypical antipsychotic clozapine is widely used for treatment-resistant
      schizophrenic patients. Clozapine and its major active metabolite, N
      desmethylclozapine (NDMC), have complex pharmacological properties, and interact
      with various neurotransmitter receptors. There are several biochemical studies
      reporting that NDMC exhibits a partial agonist profile at the human recombinant
      M1 muscarinic receptors. However, direct electrophysiological evidence showing
      the ability of NDMC to activate native M1 receptors in intact neurons is poor.
      Using rat hippocampal neurons, we previously demonstrated that activation of
      muscarinic receptors by a muscarinic agonist, oxotremorine M (oxo-M), induces a
      decrease in outward K(+)current at -40mV. In the present study, using this
      muscarinic current response we assessed agonist and antagonist activities of
      clozapine and NDMC at native muscarinic receptors in intact hippocampal
      excitatory and inhibitory neurons. Suppression of the oxo-M-induced current
      response by the M1 antagonist pirenzepine was evident only in excitatory neurons,
      while the M3 antagonist darifenacin was effective in both types of neurons.
      Muscarinic agonist activity of NDMC was higher than that of clozapine, higher in
      excitatory neurons than in inhibitory neurons, sensitive to pirenzepine, and
      partially masked when co-applied with clozapine. Muscarinic antagonist activity
      of clozapine as well as NDMC was not different between excitatory and inhibitory
      neurons, but clozapine was more effective than NDMC. These results demonstrate
      that NDMC has the ability to activate native M1 receptors expressed in
      hippocampal excitatory neurons, but its agonist activity might be limited in
      clozapine-treated patients because of the presence of excessive clozapine with
      muscarinic antagonist activity.

PMID- 27048747
TI  - Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well
      controlled HIV Replication and R5-tropic Virus on Their First
      Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted
      Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH
      Study.
AB  - BACKGROUND: Alternative combination antiretroviral therapies in virologically
      suppressed human immunodeficiency virus (HIV)-infected patients experiencing side
      effects and/or at ongoing risk of important comorbidities from current therapy
      are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential
      alternative component of therapy in those with R5-tropic virus. METHODS: The
      Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch
      study in HIV type 1-infected adults with R5-tropic virus, virologically
      suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double
      nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone.
      Participants were randomized 1:2:2 to current combination antiretroviral therapy
      (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the
      nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice
      daily MVC. The primary endpoint was the difference (switch minus control) in
      proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch
      arms were judged noninferior if the lower limit of the 95% confidence interval
      (CI) for the difference in the primary endpoint was < -12% in the intention-to
      treat (ITT) population. RESULTS: The ITT population comprised 395 participants
      (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline
      characteristics were well matched. At week 48, noninferior rates of virological
      suppression were observed in those switching away from a PI/r (93.6% [95% CI, 
      9.0% to 2.2%] and 91.7% [95% CI, -9.6% to 3.8%] with VL <200 and <50 copies/mL,
      respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50
      copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority
      bounds and was significantly inferior (84.1% [95% CI, -19.8% to -5.8%] and 77.7%
      [95% CI, -24.9% to -8.4%] with VL <200 and <50 copies/mL, respectively) to the
      control arm in the ITT analysis. CONCLUSIONS: These data support MVC as a switch
      option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but
      not as part of N(t)RTI-sparing regimens comprising MVC with PI/r. CLINICAL TRIALS
      REGISTRATION: NCT01384682.

PMID- 27048753
TI  - V63 and N65 of overexpressed alpha-synuclein are involved in mitochondrial
      dysfunction.
AB  - Parkinson's Disease (PD) is one of the most common neurodegenerative diseases.
      alpha-Synuclein (alpha-Syn)-encoded by SNCA, the first-identified PD-related gene
      is the main component of Lewy bodies, which are a pathological hallmark of PD. We
      previously reported that alpha-Syn accumulates in mitochondria in PD, causing
      mitochondrial abnormalities and disrupting mitochondrial membrane potential
      (Deltapsim) and mitochondrial potential transition pore (mPTP) opening by
      interacting with the voltage-dependent anion channel (VDAC) and adenine
      nucleotide translocator. However, the mechanistic basis of mitochondrial
      impairment caused by alpha-Syn has yet to be elucidated. It has been suggested
      that the amino acid residues Q62, V63, and N65 of alpha-Syn are important for the
      interaction of the protein with membranes. To investigate whether this underlies
      the mitochondrial dysfunction induced by alpha-Syn overexpression, we mutated
      these residues to alanine and transfected HEK293T and MN9D cells with the mutated
      forms of alpha-Syn protein. The V63A and N65A mutations prevented mitochondrial
      Ca(2+) overload and Deltapsim dysregulation as well as complex I inactivation and
      reactive oxygen species production while blocking mPTP opening and caspase 9
      activation, possibly by reducing alpha-Syn accumulation in mitochondria. These
      results indicate that V63 and N65 are critical residues mediating mitochondrial
      inactivation. These findings provide novel insight into the molecular events
      contributing to PD pathogenesis.

PMID- 27048755
TI  - Ethical foundations of environmental radiological protection.
AB  - Assessing the potential ecological impact of ionising radiation raises a number
      of ethical questions. These include fundamental questions such as what exactly
      constitutes harming the environment, and how the environment should be valued, as
      well as links to political protection principles such as sustainability and
      biodiversity. Starting from developments within ecological risk assessment, this
      paper summarises some of the ethical issues concerning the protection of the
      environment from radiation. Chapter 2 gives a brief overview of different
      philosophical and cultural world views on valuing the environment in a context of
      radiation risk. Chapter 3 addresses some recent challenges to proposed
      environmental protection frameworks, including practical applications following
      the Chernobyl and Fukushima accidents, and some scientific developments such as
      the ecosystem approach. Finally, Chapter 4 offers some recommendations on how
      ethical evaluation can help produce a more robust and transparent approach to the
      protection of the environment. In conclusion, there is a need for a holistic
      evaluation of the environmental impacts of ionising radiation that not only
      considers the direct consequences on the health of humans and non-human species,
      but also the more complex social, ethical, and economic consequences of both
      human and non-human exposures. 

PMID- 27048756
TI  - ICRP dose coefficients: computational development and current status.
AB  - Major current efforts within Committee 2 of the International Commission on
      Radiological Protection (ICRP) involve the development of dose coefficients for
      inhalation and ingestion of radionuclides, and those for exposure to
      environmental radiation fields. These efforts build upon changes in radiation and
      tissue weighting factors (Publication 103), radionuclide decay schemes
      (Publication 107), computational phantoms of the adult reference male and female
      (Publication 110), external dose coefficients for adult reference workers for
      idealised radiation fields (Publication 116), models of radionuclide intake
      (Publications 66, 100 and 130), and models of radionuclide systemic biokinetics
      (Publication 130). This paper will review the overall computational framework for
      both internal and external dose coefficients. For internal exposures, the work
      entails assessment of organ self-dose and cross-dose from monoenergetic particle
      emissions (specific absorbed fraction), absorbed dose per nuclear transformation
      (S value), time-integrated activity of the radionuclide in source tissues
      (inhalation, ingestion, and systemic biokinetic models), and their numerical
      combination to yield the organ equivalent dose or effective dose per activity
      inhaled or ingested. Various challenges are reviewed that were not included in
      the development of Publication 30 dose coefficients, which were based upon much
      more simplified biokinetic models and computational phantoms. For external
      exposures, the computations entail the characterisation of environmental
      radionuclide distributions, the transport of radiation particles through that
      environment, and the tracking of energy deposition to the organs of the exposed
      individual. Progress towards the development of dose coefficients to members of
      the general public (adolescents, children, infants and fetuses) are also
      reviewed. 

PMID- 27048754
TI  - Chronic intermittent ethanol exposure during adolescence: Effects on stress
      induced social alterations and social drinking in adulthood.
AB  - We previously observed lasting and sex-specific detrimental consequences of early
      adolescent intermittent ethanol exposure (AIE), with male, but not female, rats
      showing social anxiety-like alterations when tested as adults. The present study
      used Sprague Dawley rats to assess whether social alterations induced by AIE
      (3.5g/kg, intragastrically, every other day, between postnatal days [P] 25-45)
      are further exacerbated by stressors later in life. Another aim was to determine
      whether AIE alone or in combination with stress influenced intake of a sweetened
      ethanol solution (Experiment 1) or a sweetened solution ("supersac") alone
      (Experiment 2) under social circumstances. Animals were exposed to restraint on
      P66-P70 (90min/day) or left nonstressed, with corticosterone (CORT) levels
      assessed on day 1 and day 5 in Experiment 2. Social anxiety-like behavior emerged
      after AIE in non-stressed males, but not females, whereas stress-induced social
      anxiety was evident only in water-exposed males and females. Adult-typical
      habituation of the CORT response to repeated restraint was not evident in adult
      animals after AIE, a lack of habituation reminiscent of that normally evident in
      adolescents. Neither AIE nor stress affected ethanol intake under social
      circumstances, although AIE and restraint independently increased adolescent
      typical play fighting in males during social drinking. Among males, the
      combination of AIE and restraint suppressed "supersac" intake; this index of
      depression-like behavior was not seen in females. The results provide
      experimental evidence associating adolescent alcohol exposure, later stress,
      anxiety, and depression, with young adolescent males being particularly
      vulnerable to long-lasting adverse effects of repeated ethanol. This article is
      part of a Special Issue entitled SI: Adolescent plasticity.

PMID- 27048758
TI  - How to ensure quality of health accounts.
AB  - Policy makers need up-to-date and reliable information to formulate health
      policies and monitor their implementation. Given that financing is one of the
      pillars of the health system, quality of financing data is essential. Quality is
      a key element but difficult to measure. Increasing quality on financing data
      involves the use of standard procedures and methods. Current standard framework,
      the System of Health Accounts 2011, needs to be implemented with checks and
      controls on the individual as well as aggregated data. Data input on the
      construction of the accounts and their related metadata are subject to quality
      measures. In this paper we address a first proposal of the components of the
      quality in health accounts reporting. The paper assesses Quality Of Health
      Accounts at four stages: (1) Design; (2) Development; (3) Management; and (4)
      Reporting. It explains what is needed at each stage to ensure reliable results
      which are fit for informing decision-making. Quality is essential for reliability
      and trust among all stakeholders, who are responsible of data provision,
      construction of the accounts and using their results. Quality measurement in
      health accounts is a reality needing effort. 

PMID- 27048757
TI  - Three-dimensional direct measurement of cardiomyocyte volume, nuclearity, and
      ploidy in thick histological sections.
AB  - Quantitative assessment of myocardial development and disease requires accurate
      measurement of cardiomyocyte volume, nuclearity (nuclei per cell), and ploidy
      (genome copies per cell). Current methods require enzymatically isolating cells,
      which excludes the use of archived tissue, or serial sectioning. We describe a
      method of analysis that permits the direct simultaneous measurement of
      cardiomyocyte volume, nuclearity, and ploidy in thick histological sections. To
      demonstrate the utility of our technique, heart tissue was obtained from four
      species (rat, mouse, rabbit, sheep) at up to three life stages: prenatal, weaning
      and adulthood. Thick (40 MUm) paraffin sections were stained with Wheat Germ
      Agglutinin-Alexa Fluor 488 to visualise cell membranes, and DAPI (4',6-diamidino
      2-phenylindole) to visualise nuclei and measure ploidy. Previous methods have
      been restricted to thin sections (2-10 MUm) and offer an incomplete picture of
      cardiomyocytes. Using confocal microscopy and three-dimensional image analysis
      software (Imaris Version 8.2, Bitplane AG, Switzerland), cardiomyocyte volume,
      nuclearity, and ploidy were measured. This method of staining and analysis of
      cardiomyocytes enables accurate morphometric measurements in thick histological
      sections, thus unlocking the potential of archived tissue. Our novel time
      efficient method permits the entire cardiomyocyte to be visualised directly in
      3D, eliminating the need for precise alignment of serial sections. 

PMID- 27048759
TI  - A comparative study of lysosome-targetable pH probes based on phenoxazinium
      attached with aliphatic and aromatic amines.
AB  - In this paper, phenoxazinium was used as a fluorophore for the design of pH
      probes by the photoinduced electron transfer (PET) mechanism. Phenoxazinium with
      an aliphatic morpholinyl group (probe ) gave increased emission at 665 nm with pH
      ranging from 7.4 to 4.4; meanwhile, the other one with an aromatic
      diethylaminophenyl group (probe ) gave nearly OFF-ON emission at 679 nm with pH
      ranging from 7.4 to 4.2. They both were reversible pH probes with good
      selectivity. Their optical properties, especially the PET mechanism, were
      illustrated by (TD)DFT theory. Fluorescence confocal imaging of probes and a
      typical phenoxazinium dye (Oxazine 1) was also performed, and the results
      indicated that probes are lysosome-targetable biomarkers.

PMID- 27048760
TI  - Near optimal graphene terahertz non-reciprocal isolator.
AB  - Isolators, or optical diodes, are devices enabling unidirectional light
      propagation by using non-reciprocal optical materials, namely materials able to
      break Lorentz reciprocity. The realization of isolators at terahertz frequencies
      is a very important open challenge made difficult by the intrinsically lossy
      propagation of terahertz radiation in current non-reciprocal materials. Here we
      report the design, fabrication and measurement of a terahertz non-reciprocal
      isolator for circularly polarized waves based on magnetostatically biased
      monolayer graphene, operating in reflection. The device exploits the non
      reciprocal optical conductivity of graphene and, in spite of its simple design,
      it exhibits almost 20 dB of isolation and only 7.5 dB of insertion loss at 2.9
      THz. Operation with linearly polarized light can be achieved using quarter-wave
      plates as polarization converters. These results demonstrate the superiority of
      graphene with respect to currently used terahertz non-reciprocal materials and
      pave the way to a novel class of optimal non-reciprocal devices. 

PMID- 27048761
TI  - Survival following accidental scarf strangulation.
AB  - Injury or death by strangulation, unless otherwise explained, is almost always
      homicidal. Accidental strangulation may occur but only very rarely. We present
      such a case of accidental strangulation and survival in a motorbike pillion
      rider. A long scarf (dupatta) clad woman, sitting at the back of a two wheeler
      motorbike, fell after her long scarf got caught in the back wheel. The lady was
      first taken to a local clinic and then later was referred to a hospital for a
      suspected spine injury where she made an uneventful recovery. This case report
      exposes the precarious position of women pillion riders wearing a long scarf and
      emphasizes the need for extra caution and the need for wheel guards on spoked
      wheels in particular. 

PMID- 27048762
TI  - DNA evidence - have we progressed in the last 10 years?

PMID- 27048763
TI  - Rational Design of Plasmonic Nanoparticles for Enhanced Cavitation and Cell
      Perforation.
AB  - Metallic nanoparticles are routinely used as nanoscale antenna capable of
      absorbing and converting photon energy with subwavelength resolution. Many
      applications, notably in nanomedicine and nanobiotechnology, benefit from the
      enhanced optical properties of these materials, which can be exploited to image,
      damage, or destroy targeted cells and subcellular structures with unprecedented
      precision. Modern inorganic chemistry enables the synthesis of a large library of
      nanoparticles with an increasing variety of shapes, composition, and optical
      characteristic. However, identifying and tailoring nanoparticles morphology to
      specific applications remains challenging and limits the development of efficient
      nanoplasmonic technologies. In this work, we report a strategy for the rational
      design of gold plasmonic nanoshells (AuNS) for the efficient ultrafast laser
      based nanoscale bubble generation and cell membrane perforation, which constitute
      one of the most crucial challenges toward the development of effective gene
      therapy treatments. We design an in silico rational design framework that we use
      to tune AuNS morphology to simultaneously optimize for the reduction of the
      cavitation threshold while preserving the particle structural integrity. Our
      optimization procedure yields optimal AuNS that are slightly detuned compared to
      their plasmonic resonance conditions with an optical breakdown threshold 30%
      lower than randomly selected AuNS and 13% lower compared to similarly optimized
      gold nanoparticles (AuNP). This design strategy is validated using time-resolved
      bubble spectroscopy, shadowgraphy imaging and electron microscopy that confirm
      the particle structural integrity and a reduction of 51% of the cavitation
      threshold relative to optimal AuNP. Rationally designed AuNS are finally used to
      perforate cancer cells with an efficiency of 61%, using 33% less energy compared
      to AuNP, which demonstrate that our rational design framework is readily
      transferable to a cell environment. The methodology developed here thus provides
      a general strategy for the systematic design of nanoparticles for nanomedical
      applications and should be broadly applicable to bioimaging and cell nanosurgery.

PMID- 27048765
TI  - Outcomes After Vena Cava Filter Use in Noncancer Patients With Acute Venous
      Thromboembolism: A Population-Based Study.
AB  - BACKGROUND: Evidence that vena cava filters (VCFs) are beneficial is limited.
      METHODS AND RESULTS: We retrospectively analyzed all noncancer patients admitted
      to nonfederal California hospitals for acute venous thromboembolism from 2005 to
      2010. Analysis was stratified by the presence/absence of a contraindication to
      anticoagulation (active bleeding, major surgery). Outcomes were death within 30
      or 90 days of admission and the 1-year incidence of recurrent venous
      thromboembolism manifested as pulmonary embolism or deep vein thrombosis.
      Propensity score methods were used to account for observed systematic differences
      in baseline characteristics between patients treated and those not treated with a
      VCF. Among 80 697 patients with no contraindication to anticoagulation, VCF use
      (n=7762, 9.6%) did not significantly reduce the 30-day risk of death (hazard
      ratio [HR], 1.12; 95% confidence interval [CI], 0.98-1.28). Among 3017 patients
      with active bleeding, VCF use (n=1095, 36.3%) reduced the 30-day risk of death by
      32% (HR, 0.68; 95% CI, 0.52-0.88) and the 90-day risk by 27% (HR, 0.73; 95% CI,
      0.59-0.90). VCF use (n=489, 33.8%) did not reduce mortality among 1445 patients
      who underwent major surgery (HR, 1.1; 95% CI, 0.71-1.77). In all subgroups,
      filter use did not reduce the risk of subsequent pulmonary embolism. However, the
      risk of subsequent deep vein thrombosis increased by 50% among VCF patients with
      no contraindication (HR, 1.53; 95% CI, 1.34-1.74) and by 135% among VCF patients
      with active bleeding (HR, 2.35; 95% CI, 1.56-3.52). CONCLUSIONS: VCF use
      significantly reduced the short-term risk of death only among patients with acute
      venous thromboembolism who had a contraindication to anticoagulation because of
      active bleeding. These results support the findings of a randomized clinical
      trial and current guidelines that recommend VCF use only in patients who cannot
      receive anticoagulation treatment.

PMID- 27048764
TI  - Burden of Systolic and Diastolic Left Ventricular Dysfunction Among Hispanics in
      the United States: Insights From the Echocardiographic Study of Latinos.
AB  - BACKGROUND: Population-based estimates of cardiac dysfunction and clinical heart
      failure (HF) remain undefined among Hispanics/Latino adults. METHODS AND RESULTS:
      Participants of Hispanic/Latino origin across the United States aged 45 to 74
      years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and
      underwent a comprehensive echocardiography examination to define left ventricular
      systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD).
      Clinical HF was defined according to self-report, and those with cardiac
      dysfunction but without clinical HF were characterized as having subclinical or
      unrecognized cardiac dysfunction. Of 1818 ECHO-SOL participants (mean age 56.4
      years; 42.6% male), 49.7% had LVSD or LVDD or both. LVSD prevalence was 3.6%,
      whereas LVDD was detected in 50.3%. Participants with LVSD were more likely to be
      males and current smokers (all P<0.05). Female sex, hypertension, diabetes
      mellitus, higher body mass index, and renal dysfunction were more common among
      those with LVDD (all P<0.05). In age-sex adjusted models, individuals of Central
      American and Cuban backgrounds were almost 2-fold more likely to have LVDD
      compared with those of Mexican backgrounds. Prevalence of clinical HF with LVSD
      (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with
      preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or
      unrecognized. Compared with those with clinical cardiac dysfunction, prevalent
      coronary heart disease was the only factor independently associated with
      subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence
      interval: 0.1-0.4). CONCLUSIONS: Among Hispanics/Latinos, most cardiac
      dysfunction is subclinical or unrecognized, with a high prevalence of diastolic
      dysfunction. This identifies a high-risk population for the development of
      clinical HF.

PMID- 27048766
TI  - Quarter variation and correlations of colostrum albumin, immunoglobulin G1 and G2
      in dairy cows.
AB  - A high variation in immunoglobulin G1 (IgG1) concentration in first milked
      quarter colostrum has been reported, but BSA quarter colostrum variation is not
      known. The occurrence of serum albumin in milk has been attributed to increased
      blood-milk barrier penetration. Reports of serum albumin binding to the Fc
      Receptor of the neonate, the receptor thought to be responsible for IgG1
      transcytosis, suggested that a correlation with the appearance of IgG1 in
      colostrum of dairy cows was likely. The objective of the study was to establish
      the quarter colostrum concentration and mass of immunoglobulins and serum
      albumin. First colostrum was quarter collected within 4 h of parturition from
      healthy udders of 31 multiparous dairy cows. Individual quarter colostrum weight
      was determined and a sample of each was frozen for subsequent analysis.
      Concentrations of immunoglobulin G1, G2, and BSA were measured by ELISA and total
      mass of components was calculated. In addition, colostrum was also analysed for L
      lactate dehydrogenase activity. Analysis of concentration and mass of BSA,
      immunoglobulin G1, G2 established that the quarter variations were different by
      cow, quarter and quarter within cow. Partial correlations corrected for colostrum
      weight indicated that BSA and IgG2 concentration and mass are closely correlated
      while that of BSA and IgG1 concentration and mass exhibited no correlation
      suggesting that BSA and IgG1 may have different transport mechanisms.
      Interestingly, immunoglobulin G1 and G2 concentration and mass exhibited strong
      correlations suggesting that also some unknown mechanism of immunoglobulin G2
      appearance in colostrum is occurring. Finally, no measured protein exhibited any
      correlation with the activity of lactate dehydrogenase in colostrum. 

PMID- 27048767
TI  - Family process and youth internalizing problems: A triadic model of etiology and
      intervention.
AB  - Despite major advances in the development of interventions for youth anxiety and
      depression, approximately 30% of youths with anxiety do not respond to cognitive
      behavioral treatment, and youth depression treatments yield modest symptom
      decreases overall. Identifying networks of modifiable risk and maintenance
      factors that contribute to both youth anxiety and depression (i.e., internalizing
      problems) may enhance and broaden treatment benefits by informing the development
      of mechanism-targeted interventions. A particularly powerful network is the rich
      array of family processes linked to internalizing problems (e.g., parenting
      styles, parental mental health problems, and sibling relationships). Here, we
      propose a new theoretical model, the triadic model of family process, to organize
      theory and evidence around modifiable, transdiagnostic family factors that may
      contribute to youth internalizing problems. We describe the model's implications
      for intervention, and we propose strategies for testing the model in future
      research. The model provides a framework for studying associations among family
      processes, their relation to youth internalizing problems, and family-based
      strategies for strengthening prevention and treatment.

PMID- 27048768
TI  - Phlebotonics for venous insufficiency.
AB  - BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by
      valvular dysfunction with or without associated obstruction, usually in the lower
      limbs. It might result in considerable discomfort with symptoms such as pain,
      itchiness and tiredness in the legs. Patients with CVI may also experience
      swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI.
      This is an update of a review first published in 2005. OBJECTIVES: To assess the
      efficacy and safety of phlebotonics administered both orally and topically for
      treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this
      update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the
      Specialised Register (August 2015), as well as the Cochrane Central Register of
      Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles
      retrieved by electronic searches were searched for additional citations. We also
      contacted pharmaceutical companies and searched the World Health Organization
      (WHO) International Clinical Trials Registry Platform Search Portal for ongoing
      studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double
      blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides,
      hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica,
      disodium flavodate, french maritime pine bark extract, grape seed extract and
      aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed the
      quality of included RCTs. We estimated the effects of treatment by using risk
      ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs),
      according to the outcome assessed. We calculated 95% confidence interval (CIs)
      and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity
      analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53
      trials provided quantifiable data (involving 6013 participants; mean age 50
      years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine,
      nine calcium dobesilate, two Centella asiatica, two aminaftone, two french
      maritime pine bark extract and one grape seed extract. No studies evaluating
      topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the
      inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced
      oedema in the lower legs compared with placebo. Phlebotonics showed beneficial
      effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to
      0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI
      -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals
      no difference in the proportion of ulcers cured with phlebotonics compared with
      placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition,
      phlebotonics showed greater efficacy for trophic disorders, cramps, restless
      legs, swelling and paraesthesia, when compared with placebo. We identified
      heterogeneity for the variables of pain, itching, heaviness, quality of life and
      global assessment by participants. For quality of life, it was not possible to
      pool the studies because heterogeneity was high. However, high-quality evidence
      suggests no differences in quality of life for calcium dobesilate compared with
      placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low
      quality evidence indicates that in the aminaftone group, quality of life was
      improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to -
      2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics
      group had greater risk of non-severe adverse events than the placebo group (RR
      1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal
      disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS:
      Moderate-quality evidence shows that phlebotonics may have beneficial effects on
      oedema and on some signs and symptoms related to CVI such as trophic disorders,
      cramps, restless legs, swelling and paraesthesia when compared with placebo but
      can produce more adverse effects. Phlebotonics showed no differences compared
      with placebo in ulcer healing. Additional high-quality RCTs focused on clinically
      important outcomes are needed to improve the evidence base.

PMID- 27048769
TI  - Perioperative transoesophageal echocardiography: current status and future
      directions.
AB  - Transoesophageal echocardiography (TOE) is used in the perioperative arena to
      monitor patients during life-threatening emergencies, cardiac and high-risk non
      cardiac surgeries. It provides qualitative and quantitative information on
      valvular and ventricular functions, and dynamic cardiac anatomy can be displayed
      with a physiological perspective. This technology has evolved from two
      dimensional (2D) to the ready availability of real-time three-dimensional (RT-3D)
      imaging in the operating rooms. Enhanced spatial and temporal resolutions with 3D
      imaging have most significantly impacted the quality of intraoperative surgical
      valve repair and replacement decisions. Additionally, 3D imaging has facilitated
      the advent of minimally invasive and percutaneous interventions for structural
      heart disease. Information derived from TEE is routinely used to evaluate a
      patient's suitability for an intervention, provide guidance during the
      intervention and eventually comment on the quality and success of the procedure.
      Expertise in perioperative TEE is an integral component of a cardiac
      anaesthesiologist's skill sets. With structural heart disease interventions
      becoming more minimally invasive, the intraoperative guidance provided by TEE
      will continue to be a critical component of these procedures. With improving
      computational and processing power, the expectations from TEE will continue to be
      incremental in the perioperative arena.

PMID- 27048770
TI  - Beyond the aortic valve: predictors of outcomes in adults with aortic stenosis.

PMID- 27048771
TI  - Obstructive sleep apnoea is associated with myocardial injury in patients with
      refractory angina.
AB  - OBJECTIVE: To investigate the association between obstructive sleep apnoea (OSA)
      severity with markers of overnight myocardial injury in patients with refractory
      angina. METHODS: Patients with refractory angina were characterised clinically
      and they underwent ischaemia imaging stress tests by single-photon emission
      computed tomography (SPECT) and/or cardiac MRI. The patients were admitted to the
      hospital, remained under resting conditions for blood determination of high
      sensitivity cardiac troponin T (hs-cTnT) at 14:00, 22:00 and after overnight
      polysomnography at 7:00. RESULTS: We studied 80 consecutive patients (age: 62+/
      10 years; male: 66%; body mass index (BMI): 29.5+/-4 kg/m(2)) with well
      established diagnosis of refractory angina. The mean apnoea-hypopnoea index (AHI)
      was 37+/-29 events/h and OSA (AHI >15 events/h) was present in 75% of the
      population. Morning detectable hs-cTnT and above 99th percentile was present in
      88% and 36% of the population, respectively. Patients in the first to third
      quartiles of OSA severity did not have circadian variation of hs-cTnT. In
      contrast, patients in the fourth quartile (AHI >=51 events/h) had a circadian
      variation of hs-cTnT with a morning peak of hs-cTnT that was two times higher
      than that in the remaining population (p=0.02). The highest quartile of OSA
      severity remained associated with the highest quartile of hs-cTnT (p=0.028) in
      multivariate analysis. CONCLUSION: Very severe OSA is common and independently
      associated with overnight myocardial injury in patients with refractory angina.

PMID- 27048772
TI  - Cardiac adaption during pregnancy in women with congenital heart disease and
      healthy women.
AB  - OBJECTIVE: Pregnancy in women with congenital heart disease (CHD) is associated
      with deterioration in cardiac function. However, longitudinal data are scarce.
      This study describes serial changes in cardiac dimensions and function during
      pregnancy in women with CHD and compares these with healthy pregnant women
      (controls). METHODS: Eight tertiary centres prospectively enrolled 125 pregnant
      women with CHD (pregnancy duration <20 weeks). Controls (N=49) were recruited
      from low-risk midwife practices. Standardised echocardiography at 20 and 32 weeks
      gestation and 1 year postpartum was performed. RESULTS: Age and parity were
      comparable between both groups (p>0.1). Left ventricular ejection fraction (LVEF)
      <45% was present in 3.2% of women with CHD and 14.4% had tricuspid annular plane
      systolic excursion (TAPSE) <16 mm. Absolute values of ventricular function
      parameters and diameters were less favourable in women with CHD. No permanent
      changes occurred in right and left ventricular function parameters and dimensions
      in women with CHD. The patterns of change in cardiac function and dimensions were
      comparable between women with CHD and controls, except for LVEF (p=0.026). In
      women with right-sided CHD the pattern of TAPSE over time differed from controls
      (p=0.043) (no decrease in TAPSE postpregnancy in CHD). In women with left-sided
      CHD left ventricular end-diastolic diameter (LVEDD) tended to increase compared
      with controls (p=0.045). CONCLUSIONS: Absolute levels of ventricular function
      parameters and diameters differ between CHD and controls, but changes during and
      after pregnancy are generally comparable. However, different patterns over time
      seen for TAPSE and LVEDD in women with right-sided and left-sided CHD,
      respectively, compared with controls indicate the importance of echocardiographic
      follow-up during pregnancy in women with CHD.

PMID- 27048773
TI  - A nationwide family study of venous thromboembolism and risk of arterial vascular
      disease.
AB  - OBJECTIVE: This nationwide study aimed to determine whether venous
      thromboembolism (VTE) shares familial susceptibility with aortic aneurysm (AA),
      peripheral artery disease (PAD) and arterial thrombosis and embolisation (ATE) in
      locations other than the heart and brain. METHODS: Nationwide Swedish family
      study. Data from the Swedish Multi-Generation Register for subjects aged 0-78
      years old, covering the period 1964-2010, were linked to the Hospital Register.
      Familial risks (standardised incidence ratio, SIR) of AA, PAD and ATE were
      determined for individuals with a first-degree relative (parents/sibling)
      diagnosed with VTE. Separate analyses were done to determine risks for spouses.
      RESULTS: A total of 13 063 individuals had AA, 15 494 had PAD and 7325 had ATE.
      Fully adjusted familial risks for individuals with family history
      (parent/sibling) of VTE were 1.04 (95% CI 1.00 to 1.08)) for AA, 1.42 (1.35 to
      1.49) for ATE and 1.08 (1.04 to 1.13) for PAD. The familial sibling risks were
      1.07 (0.99 to 1.14) for AA, 1.61 (1.48 to 1.74) for ATE and 1.19 (1.11 to 1.26)
      for PAD. Among individuals younger than 50 years of age, the familial risks were:
      1.13 (0.99 to 1.29) for AA, 1.76 (1.62 to 1.91) for ATE and 1.12 (1.03 to 1.21)
      for PAD. In spouses of patients with VTE, the SIRs were 1.21 (1.17 to 1.25) for
      AA, 1.19 (1.14 to 1.23) for ATE and 1.26 (1.21 to 1.30) for PAD. CONCLUSIONS: VTE
      shares only weak familial susceptibility with AA and PAD in the Swedish
      population. However, ATE partially shares a moderate familial susceptibility and
      possibly genetic factors with VTE. Moreover, familial non-genetic factors may
      contribute to the observed familial associations.

PMID- 27048774
TI  - Echocardiographic predictors of outcomes in adults with aortic stenosis.
AB  - OBJECTIVE: The study purpose was to assess the usefulness of echocardiographic
      parameters of aortic stenosis (AS) severity and left ventricular (LV) systolic
      function to predict mortality in AS. The main hypothesis is that parameters of LV
      systolic function are the most important independent predictors of mortality,
      whereas parameters of stenosis severity are not. METHODS: 1065 consecutive
      patients with AS referred to the echocardiography laboratory and meeting the
      inclusion/exclusion criteria were included and followed during 5.7 years. The end
      points were aortic valve replacement (AVR) (n=584), composite of AVR or death
      (n=932), all-cause mortality (n=550) and cardiovascular mortality (n=398).
      RESULTS: The most powerful echocardiographic predictors of valve-related events
      were parameters of AS severity, such as peak aortic jet velocity (VPeak), mean
      gradient (MG) and aortic valve area (AVA) (all p<0.001). Regarding mortality, the
      main predictors were LV ejection fraction (LVEF) and stroke volume index (SVi)
      (p<0.05). After multivariable adjustment, LVEF (p<0.001) and SVi (p=0.02)
      remained the only echocardiographic predictors of mortality, even after
      adjustment for symptomatic status. AVA was also associated with mortality,
      whereas VPeak and MG were not. CONCLUSIONS: The most powerful echocardiographic
      predictors of mortality are low LVEF and low flow, whereas AS severity parameters
      predict valve-related events but not overall mortality. Hence, low flow should be
      integrated in the risk stratification and therapeutic decision-making in patients
      with AS.

PMID- 27048775
TI  - Short cationic lipopeptides as effective antibacterial agents: Design,
      physicochemical properties and biological evaluation.
AB  - The spread of drug-resistant bacteria has imparted a sense of urgency in the
      search for new antibiotics. In an effort to develop a new generation of
      antibacterial agents, we have designed de novo charged lipopeptides inspired by
      natural antimicrobial peptides. These short lipopeptides are composed of cationic
      lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties
      of natural antimicrobial peptides. The resultant lipopeptides were found to self
      assemble into nanoparticles. Some were effective against a variety of Gram
      positive bacteria, including strains resistant to methicillin, daptomycin and/or
      vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines
      and were highly resistant to tryptic degradation. Transmission electron
      microscopy analysis of bacteria cells treated with lipopeptide showed membrane
      damage and lysis with extrusion of cytosolic contents. With such properties in
      mind, these lipopeptides have the potential to be developed as new antibacterial
      agents against drug-resistant Gram-positive bacteria.

PMID- 27048776
TI  - Mercury anomalies and the timing of biotic recovery following the end-Triassic
      mass extinction.
AB  - The end-Triassic mass extinction overlapped with the eruption of the Central
      Atlantic Magmatic Province (CAMP), and release of CO2 and other volcanic
      volatiles has been implicated in the extinction. However, the timing of marine
      biotic recovery versus CAMP eruptions remains uncertain. Here we use Hg
      concentrations and isotopes as indicators of CAMP volcanism in continental shelf
      sediments, the primary archive of faunal data. In Triassic-Jurassic strata,
      Muller Canyon, Nevada, Hg levels rise in the extinction interval, peak before the
      appearance of the first Jurassic ammonite, remain above background in association
      with a depauperate fauna, and fall to pre-extinction levels during significant
      pelagic and benthic faunal recovery. Hg isotopes display no significant mass
      independent fractionation within the extinction and depauperate intervals,
      consistent with a volcanic origin for the Hg. The Hg and palaeontological
      evidence from the same archive indicate that significant biotic recovery did not
      begin until CAMP eruptions ceased. 

PMID- 27048777
TI  - Occurrence, spatiotemporal distribution, mass balance and ecological risks of
      antibiotics in subtropical shallow Lake Taihu, China.
AB  - The objective of this study was to evaluate the occurrence, spatiotemporal
      distribution, mass balance and ecological risks of 43 commonly used human and
      veterinary antibiotics in both aqueous and sedimentary phases in a large
      subtropical shallow lake, Lake Taihu. In the aqueous phase, sulfonamides (2.64
      344 ng L(-1)), lincomycin (ND to 53.8 ng L(-1)) and florfenicol (0.15-963 ng L(
      1)) were the main compounds with high concentrations and detection frequencies.
      In the sedimentary phase, fluoroquinolones (ND to 174 ng g(-1), dry weight) and
      tetracyclines (ND to 39.6 ng g(-1), dry weight) were the predominant compounds.
      Antibiotic concentrations in Lake Taihu were generally lower relative to data
      documented in previous studies on China and other countries. The composition of
      antibiotics showed that livestock wastewater might be the main source of
      antibiotics in Lake Taihu, followed by domestic wastewater. Antibiotics in the
      lake water showed slight spatial variation in summer and significant spatial
      variation in winter; whereas, antibiotic concentrations in the sediments varied
      obviously, with high concentrations found in the sites close to potential
      pollution sources. Mass balance showed that sediments are an important sink and
      potential source for fluoroquinolones and tetracyclines. In addition to
      antibiotics' physicochemical properties, the spatiotemporal distribution of
      antibiotics in the lake was influenced by both pollution sources and lake
      hydrodynamics. The environmental risk assessment results showed that
      sulfamethoxazole could pose high risks on the algae in the aquatic ecosystem,
      followed by tetracyclines (algae) and fluoroquinolones (bacteria). Overall, our
      study reveals complex compositions and clear spatiotemporal dynamics in Lake
      Taihu, which were the consequence of pollution sources and lake hydrodynamics. 

PMID- 27048778
TI  - Milk production in dairy goats supplemented with different levels of ruminally
      protected methionine.
AB  - The objective of the study reported in this Research Communication was to
      evaluate graded levels of ruminally protected methionine (RPM) in dairy goat
      rations on milk production and live weight changes during 155 d of lactation.
      Twenty-five primiparous dairy goats (crosses of Toggenburg, French Alpine and
      Saanen; 45.4 +/- 1.0 kg BW) were fed a basal diet (10.10% CP, 6.13 DP and 2.34
      Mcal/kg ME) of corn silage, oat hay, alfalfa hay and concentrate (80% forage, 20%
      concentrate). After kidding, the treatments, which consisted of four oral doses
      of ruminally protected methionine (RPM) at 0, 1, 2 and 3 g/d, were randomly
      assigned to the goats. The experiment was conducted for 110 d with measurements
      of milk production and composition, body weight and dry matter intake. No
      treatment effects were detected in milk production and composition. However,
      goats with RPM showed a positive live weight changes during lactation which were
      improved as dose was increased (linear P < 0.01) whereas goats without RPM showed
      weight loss during the experiment. 

PMID- 27048779
TI  - Strontium-90 activity concentration in soil samples from the exclusion zone of
      the Fukushima daiichi nuclear power plant.
AB  - The radioactive fission product (90)Sr has a long biological half-life (~18 y) in
      the human body. Due to its chemical similarity to calcium it accumulates in bones
      and irradiates the bone marrow, causing its high radio-toxicity. Assessing (90)Sr
      is therefore extremely important in case of a nuclear disaster. In this work 16
      soil samples were collected from the exclusion zone (<30 km) of the earthquake
      damaged Fukushima Daiichi nuclear power plant, to measure (90)Sr activity
      concentration using liquid scintillation counting. (137)Cs activity concentration
      was also measured with gamma-spectroscopy in order to investigate correlation
      with (90)Sr. The (90)Sr activity concentrations ranged from 3.0 +/- 0.3 to 23.3
      +/- 1.5 Bq kg(-1) while the (137)Cs from 0.7 +/- 0.1 to 110.8 +/- 0.3 kBq kg(-1).
      The fact that radioactive contamination originated from the Fukushima nuclear
      accident was obvious due to the presence of (134)Cs. However, (90)Sr
      contamination was not confirmed in all samples although detectable amounts of
      (90)Sr can be expected in Japanese soils, as a background, stemming from global
      fallout due to the atmospheric nuclear weapon tests. Correlation analysis between
      (90)Sr and (137)Cs activity concentrations provides a potentially powerful tool
      to discriminate background (90)Sr level from its Fukushima contribution. 

PMID- 27048780
TI  - Influence of age on seven putative prostate tumor markers: a cohort study in
      Chinese men.
AB  - The accuracy and sensitivity of prostate-specific antigen (PSA) for prostate
      cancer diagnosis is often poor; however, the reasons for its inaccuracy have
      rarely been investigated, especially with respect to age. In this study, 476
      healthy males, aged 10-89 years, were stratified into eight age groups, and
      levels of seven markers were determined: total PSA (tPSA), free PSA (fPSA),
      %fPSA, isoform [-2]proPSA (p2PSA), p2PSA/tPSA, %p2PSA, and the prostate health
      index (PHI). Both tPSA and fPSA levels increased with age. The tPSA level was
      highest (1.39 ng ml-1) at 70-79 years; %fPSA was highest (0.57 ng ml-1) at 10-19
      years; and %p2PSA was lowest (18.33 ng ml-1) at 40-49 years. Both p2PSA and
      p2PSA/tPSA had relatively flat curves and showed no correlation with age (P =
      0.222). PHI was a sensitive age-associated marker (P < 0.05), with two peaks and
      one trough. The coverage rates and radiance graphs of PHI and %p2PSA were more
      distinctive than those of tPSA and the other markers. In subjects older than 69
      years, PHI and %p2PSA both began to decrease, approximately 10 years earlier than
      the decrease in tPSA. Our results suggest that the clinical diagnosis of prostate
      cancer using PSA should be investigated more comprehensively based on patient
      age. Moreover, %p2PSA and PHI could be considered as earlier markers that may be
      more suitable than PSA alone.

PMID- 27048781
TI  - Advances in the management of infertility in men with spinal cord injury.
AB  - Couples with a spinal cord injured male partner require assisted ejaculation
      techniques to collect semen that can then be further used in various assisted
      reproductive technology methods to achieve a pregnancy. The majority of men
      sustaining a spinal cord injury regardless of the cause or the level of injury
      cannot ejaculate during sexual intercourse. Only a small minority can ejaculate
      by masturbation. Penile vibratory stimulation and electroejaculation are the two
      most common methods used to retrieve sperm. Other techniques such as prostatic
      massage and the adjunct application of other medications can be used, but the
      results are inconsistent. Surgical sperm retrieval should be considered as a last
      resort if all other methods fail. Special attention must be paid to patients with
      T6 and rostral levels of injury due to the risk of autonomic dysreflexia
      resulting from stimulation below the level of injury. Bladder preparation should
      be performed before stimulation if retrograde ejaculation is anticipated.
      Erectile dysfunction is ubiquitous in the spinal cord injured population but is
      usually easily managed and does not pose a barrier to semen retrieval in these
      men. Semen analysis parameters of men with spinal cord injury are unique for this
      population regardless of the method of retrieval, generally presenting as normal
      sperm concentration but abnormally low sperm motility and viability. When sperm
      retrieval is desired in this population, emphasis should be placed on initially
      trying the simple methods of penile vibratory stimulation or electroejaculation
      before resorting to more advanced and invasive surgical procedures. 

PMID- 27048783
TI  - Basic concepts and recent advancements in the study of male fertility.

PMID- 27048782
TI  - Recent advances in the genetics of testicular failure.
AB  - Infertility affects approximately 15% of couples, and male factor is responsible
      for 30%-50% of all infertility. The most severe form of male infertility is
      testicular failure, and the typical phenotype of testicular failure is severely
      impaired spermatogenesis resulting in azoospermia or severe oligozoospermia.
      Although the etiology of testicular failure remains poorly understood, genetic
      factor typically is an underlying cause. Modern assisted reproductive techniques
      have revolutionized the treatment of male factor infertility, allowing biological
      fatherhood to be achieved by many men who would otherwise have been unable to
      become father to their children through natural conception. Therefore,
      identifying genetic abnormalities in male is critical because of the potential
      risk of transmission of genetic abnormalities to the offspring. Recently, along
      with other intense researches ongoing, whole-genome approaches have been used
      increasingly in the genetic studies of male infertility. In this review, we focus
      on the genetics of testicular failure and provide an update on the advances in
      the study of genetics of male infertility. 

PMID- 27048784
TI  - The importance of understanding baseline reproductive function prior to the
      administration of exogenous testosterone.

PMID- 27048785
TI  - Estradiol exerts alterations in sexual function and fertility in human males.

PMID- 27048786
TI  - Use of testicular sperm to combat the negative effects of DNA fragmentation.

PMID- 27048787
TI  - Advancement of male health is dependent upon updates to insurance coverage for
      infertility in the United States.

PMID- 27048788
TI  - The importance of sexual function in men with spinal cord injuries.

PMID- 27048789
TI  - Azoospermia and the cancer patient: are there any options?

PMID- 27048790
TI  - Sperm morphology and reproductive success.

PMID- 27048791
TI  - Ni on the CeO2(110) and (100) surfaces: adsorption vs. substitution effects on
      the electronic and geometric structures and oxygen vacancies.
AB  - We report density functional theory (DFT) calculations of the interactions of
      both Ni adsorbate and substitutional dopant with the ceria (110) and (100)
      surfaces to explain the origin of the activity of Ni/ceria catalysts. Our results
      indicate that the Ni adatom on the (110) surface prefers to adsorb on a two-fold
      bridge site over a hollow site up to 0.25 ML coverage, and the most stable
      position of a Ni adsorbate on the (100) surface was found to be the bridge site
      where the Ni atom is coordinated to two surface O atoms. The Ni(+) oxidation
      state for the Ni adatom on the (110) surface was found to be more favorable than
      the Ni(2+) state on the two-fold bridge site while on the (100) surface, a Ni
      adatom prefers its Ni(2+) oxidation state over the Ni(+) oxidation state. With
      increasing coverage, the binding energy of a Ni adatom on the (110) surface was
      found to decrease from -0.45 eV at 0.083 ML coverage to -0.32 eV at 0.25 ML
      coverage. Oxidation of the Ni adatom to Ni(+) reduces one Ce(4+) ion on the ceria
      surface to Ce(3+) which preferred to be located next to the Ni(+) ion in the
      nearest neighbor location. The Ce(3+) ions on the (100) surface also prefer to
      stay in the vicinity of the adsorbed Ni atom, while they prefer to be located
      away from the Ni adatom on the (111) surface. No reduction of Ce(4+) ions was
      observed upon substitution of Ce atoms by Ni atoms. Two Ni substituents preferred
      to be distributed on adjacent metal ion sites on the (110) surface. Ni adsorbate
      and substituent on the (110) surface were both found to induce significant
      structural distortions. In comparison to the pure ceria (110) and (100) surfaces,
      we show that a Ni adsorbate increases the energy required to create an oxygen
      vacancy while a Ni dopant reduces it. While multiple dopants on the (110) surface
      do reduce the vacancy formation energy, the degree of reduction is smaller
      compared to a single dopant indicating the presence of an optimum level of doping
      to obtain enhanced catalytic activity. 

PMID- 27048792
TI  - Ndfip2 is a potential regulator of the iron transporter DMT1 in the liver.
AB  - The regulation of divalent metal ion transporter DMT1, the primary non-heme iron
      importer in mammals, is critical for maintaining iron homeostasis. Previously we
      identified ubiquitin-dependent regulation of DMT1 involving the Nedd4 family of
      ubiquitin ligases and the Ndfip1 and Ndfip2 adaptors. We also established the in
      vivo function of Ndfip1 in the regulation of DMT1 in the duodenum of mice. Here
      we have studied the function of Ndfip2 using Ndfip2-deficient mice. The DMT1
      protein levels in the duodenum were comparable in wild type and Ndfip2(-/-) mice,
      as was the transport activity of isolated enterocytes. A complete blood
      examination showed no significant differences between wild type and Ndfip2(-/-)
      mice in any of the hematological parameters measured. However, when fed a low
      iron diet, female Ndfip2(-/-) mice showed a decrease in liver iron content,
      although they maintained normal serum iron levels and transferrin saturation,
      compared to wild type female mice that showed a reduction in serum iron and
      transferrin saturation. Ndfip2(-/-) female mice also showed an increase in DMT1
      expression in the liver, with no change in male mice. We suggest that Ndfip2
      controls DMT1 in the liver with female mice showing a greater response to altered
      dietary iron than the male mice. 

PMID- 27048794
TI  - Hybrid 3D structures of ZnO nanoflowers and PdO nanoparticles as a highly
      selective methanol sensor.
AB  - The present study concerns the enhancement of methanol selectivity of three
      dimensional (3D) nanoflowers (NFs) of ZnO by dispersing nickel oxide (NiO) and
      palladium oxide (PdO) nanoparticles on the surface of the nanoflowers to form
      localized hybrid nano-junctions. The nanoflowers were fabricated through a liquid
      phase deposition technique and the modification was achieved by addition of NiCl
      and PdCl2 solutions. In addition to the detailed structural (like X-ray
      diffraction (XRD), electron dispersive spectroscopy (EDS), X-ray mapping, XPS)
      and morphological characterization (by field emission scanning electron
      microscopy (FESEM)), the existence of different defect states (viz. oxygen
      vacancy) was also confirmed by photoluminescence (PL) spectroscopy. The sensing
      properties of the pristine and metal oxide nanoparticle (NiO/PdO)-ZnO NF hybrid
      sensor structures, towards different alcohol vapors (methanol, ethanol, 2
      propanol) were investigated in the concentration range of 0.5-700 ppm at 100-350 
      degrees C. Methanol selectivity study against other interfering species, viz.
      ethanol, 2-propanol, acetone, benzene, xylene and toluene was also investigated.
      It was found that the PdO-ZnO NF hybrid system offered enhanced selectivity
      towards methanol at low temperature (150  degrees C) compared to the NiO-ZnO NF
      and pristine ZnO NF counterparts. The underlying mechanism for such improvement
      has been discussed with respective energy band diagram and preferential
      dissociation of target species on such 3D hybrid structures. The corresponding
      improvement in transient characteristics has also been co-related with the
      proposed model.

PMID- 27048793
TI  - Intracranial Pressure Assessment in Traumatic Head Injury with Hemorrhage Via
      Optic Nerve Sheath Diameter.
AB  - Our purpose was to improve the technique of measuring optic nerve sheath diameter
      (ONSD) for intracranial pressure (ICP) monitoring in cases of traumatic head
      injury with hemorrhage. In a retrospective study, computed tomography (CT) data
      of 312 adult patients were collected and analyzed. ONSDs were measured at 3 mm
      and 8-10 mm distance from the globe together with the eyeball transverse diameter
      (ETD). The ONSD/ETD ratio was calculated. The correlation analysis was performed
      with gender, age, Glasgow Coma Scale score, and Glasgow Outcome Score. ONSD was
      enlarged in all cases when CT scans indicated hematoma. Enlarged right/left ONSDs
      were 6.5 +/- 1.5/6.4 +/- 1.3 mm at 3 mm and 6.6 +/- 0.8/6.6 +/- 0.6 mm at 8-10 mm
      from the globe (cut-off value > 5.5 mm). ONSD/ETD ratio was 0.29 +/- 0.05,
      compared with 0.19 +/- 0.02 in healthy adults (p < 0.01). We did not find a
      correlation between ONSD/ETD ratio and initial Glasgow Coma Scale score, but
      there was an inverse correlation between ONSD/ETD ratio and Glasgow Outcome Score
      (r = -0.83). We conclude that in cases with a traumatic head injury with
      hemorrhage, the ONSD is significantly enlarged, indicating elevated ICP. In ICP
      assessment, the most accurate results can be obtained if the ONSD is measured 8
      10 mm from the globe and the ONSD/ETD ratio is calculated.

PMID- 27048795
TI  - Singly Flagellated Pseudomonas aeruginosa Chemotaxes Efficiently by Unbiased
      Motor Regulation.
AB  - Pseudomonas aeruginosais an opportunistic human pathogen that has long been known
      to chemotax. More recently, it has been established that chemotaxis is an
      important factor in the ability ofP. aeruginosato make biofilms. Genes that
      allowP. aeruginosato chemotax are homologous with genes in the paradigmatic model
      organism for chemotaxis,Escherichia coli However,P. aeruginosais singly
      flagellated andE. colihas multiple flagella. Therefore, the regulation of
      counterclockwise/clockwise flagellar motor bias that allowsE. colito efficiently
      chemotax by runs and tumbles would lead to inefficient chemotaxis byP.
      aeruginosa, as half of a randomly oriented population would respond to a
      chemoattractant gradient in the wrong sense. HowP. aeruginosaregulates flagellar
      rotation to achieve chemotaxis is not known. Here, we analyze the swimming
      trajectories of single cells in microfluidic channels and the rotations of cells
      tethered by their flagella to the surface of a variable-environment flow cell. We
      show thatP. aeruginosachemotaxes by symmetrically increasing the durations of
      both counterclockwise and clockwise flagellar rotations when swimming up the
      chemoattractant gradient and symmetrically decreasing rotation durations when
      swimming down the chemoattractant gradient. Unlike the case forE. coli, the
      counterclockwise/clockwise bias stays constant forP. aeruginosa We describeP.
      aeruginosa's chemotaxis using an analytical model for symmetric motor regulation.
      We use this model to do simulations that show that, givenP. aeruginosa's
      physiological constraints on motility, its distinct, symmetric regulation of
      motor switching optimizes chemotaxis. IMPORTANCE: Chemotaxis has long been known
      to strongly affect biofilm formation by the opportunistic human pathogenP.
      aeruginosa, whose essential chemotaxis genes have homologues inE. coli, which
      achieves chemotaxis by biasing the relative probability of counterclockwise and
      clockwise flagellar rotation. However, the physiological difference between
      multiflagellatedE. coliand singly flagellatedP. aeruginosaimplies that biased
      motor regulation should preventP. aeruginosapopulations from chemotaxing
      efficiently. Here, we used experiments, analytical modeling, and simulations to
      demonstrate thatP. aeruginosauses unbiased, symmetric regulation of the flagellar
      motor to maximize its chemotaxis efficiency. This mode of chemotaxis was not
      previously known and demonstrates a new variant of a paradigmatic signaling
      system in an important human pathogen.

PMID- 27048796
TI  - Adaptor Scaffoldins: An Original Strategy for Extended Designer Cellulosomes,
      Inspired from Nature.
AB  - Designer cellulosomes consist of chimeric cohesin-bearing scaffoldins for the
      controlled incorporation of recombinant dockerin-containing enzymes. The largest
      designer cellulosome reported to date is a chimeric scaffoldin that contains 6
      cohesins. This scaffoldin represented a technical limit of sorts, since adding
      another cohesin proved problematic, owing to resultant low expression levels,
      instability (cleavage) of the scaffoldin polypeptide, and limited numbers of
      available cohesin-dockerin specificities-the hallmark of designer cellulosomes.
      Nevertheless, increasing the number of enzymes integrated into designer
      cellulosomes is critical, in order to further enhance degradation of plant cell
      wall material. Adaptor scaffoldins comprise an intermediate type of scaffoldin
      that can both incorporate various enzymes and attach to an additional scaffoldin.
      Using this strategy, we constructed an efficient form of adaptor scaffoldin that
      possesses three type I cohesins for enzyme integration, a single type II dockerin
      for interaction with an additional scaffoldin, and a carbohydrate-binding module
      for targeting to the cellulosic substrate. In parallel, we designed a hexavalent
      scaffoldin capable of connecting to the adaptor scaffoldin by the incorporation
      of an appropriate type II cohesin. The resultant extended designer cellulosome
      comprised 8 recombinant enzymes-4 xylanases and 4 cellulases-thereby representing
      a potent enzymatic cocktail for solubilization of natural lignocellulosic
      substrates. The contribution of the adaptor scaffoldin clearly demonstrated that
      proximity between the two scaffoldins and their composite set of enzymes is
      crucial for optimized degradation. After 72 h of incubation, the performance of
      the extended designer cellulosome was determined to be approximately 70% compared
      to that of native cellulosomes. IMPORTANCE: Plant cell wall residues represent a
      major source of renewable biomass for the production of biofuels such as ethanol
      via breakdown to soluble sugars. The natural microbial degradation process,
      however, is inefficient for achieving cost-effective processes in the conversion
      of plant-derived biomass to biofuels, either from dedicated crops or human
      generated cellulosic wastes. The accumulation of the latter is considered a major
      environmental pollutant. The development of designer cellulosome nanodevices for
      enhanced plant cell wall degradation thus has major impacts in the fields of
      environmental pollution, bioenergy production, and biotechnology in general. The
      findings reported in this article comprise a true breakthrough in our capacity to
      produce extended designer cellulosomes via synthetic biology means, thus enabling
      the assembly of higher-order complexes that can supersede the number of enzymes
      included in a single multienzyme complex.

PMID- 27048797
TI  - Diversified mcr-1-Harbouring Plasmid Reservoirs Confer Resistance to Colistin in
      Human Gut Microbiota.
AB  - Colistin is an ultimate line of refuge against multidrug-resistant Gram-negative
      pathogens. Very recently, the emergence of plasmid-mediatedmcr-1colistin
      resistance has become a great challenge to global public health, raising the
      possibility that dissemination of themcr-1gene is underestimated and diversified.
      Here, we report three cases of plasmid-carried MCR-1 colistin resistance in
      isolates from gut microbiota of diarrhea patients. Structural and functional
      analyses determined that the colistin resistance is conferred purely by the
      singlemcr-1gene. Genetic and sequence mapping revealed thatmcr-1-harbouring
      plasmid reservoirs are present in diversity. Together, the data represent the
      first evidence of diversity inmcr-1-harbouring plasmid reservoirs of human gut
      microbiota. IMPORTANCE: The plasmid-mediated mobile colistin resistance gene (mcr
      1) challenged greatly the conventional idea mentioned above that colistin is an
      ultimate line of refuge against lethal infections by multidrug-resistant Gram
      negative pathogens. It is a possibility that diversified dissemination of themcr
      1gene might be greatly underestimated. We report three cases of plasmid-carried
      MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients
      and functionally define the colistin resistance conferred purely by the singlemcr
      1gene. Genetic and sequence mapping revealed unexpected diversity among themcr-1
      harbouring plasmid reservoirs of human gut microbiota.

PMID- 27048798
TI  - SpoVG Is a Conserved RNA-Binding Protein That Regulates Listeria monocytogenes
      Lysozyme Resistance, Virulence, and Swarming Motility.
AB  - In this study, we sought to characterize the targets of the abundant Listeria
      monocytogenes noncoding RNA Rli31, which is required for L. monocytogenes
      lysozyme resistance and pathogenesis. Whole-genome sequencing of lysozyme
      resistant suppressor strains identified loss-of-expression mutations in the
      promoter of spoVG, and deletion of spoVG rescued lysozyme sensitivity and
      attenuation in vivo of the rli31 mutant. SpoVG was demonstrated to be an RNA
      binding protein that interacted with Rli31 in vitro. The relationship between
      Rli31 and SpoVG is multifaceted, as both the spoVG-encoded protein and the spoVG
      5'-untranslated region interacted with Rli31. In addition, we observed that spoVG
      deficient bacteria were nonmotile in soft agar and suppressor mutations that
      restored swarming motility were identified in the gene encoding a major RNase in
      Gram-positive bacteria, RNase J1. Collectively, these findings suggest that SpoVG
      is similar to global posttranscriptional regulators, a class of RNA-binding
      proteins that interact with noncoding RNA, regulate genes in concert with RNases,
      and control pleiotropic aspects of bacterial physiology. IMPORTANCE: spoVG is
      widely conserved among bacteria; however, the function of this gene has remained
      unclear since its initial characterization in 1977. Mutation of spoVG impacts
      various phenotypes in Gram-positive bacteria, including methicillin resistance,
      capsule formation, and enzyme secretion in Staphylococcus aureus and also
      asymmetric cell division, hemolysin production, and sporulation in Bacillus
      subtilis. Here, we demonstrate that spoVG mutant strains of Listeria
      monocytogenes are hyper-lysozyme resistant, hypervirulent, nonmotile, and
      misregulate genes controlling carbon metabolism. Furthermore, we demonstrate that
      SpoVG is an RNA-binding protein. These findings suggest that SpoVG has a role in
      L. monocytogenes, and perhaps in other bacteria, as a global gene regulator.
      Posttranscriptional gene regulators help bacteria adapt to various environments
      and coordinate differing aspects of bacterial physiology. SpoVG may help the
      organism coordinate environmental growth and virulence to survive as a
      facultative pathogen.

PMID- 27048799
TI  - Deacetylation of Fungal Exopolysaccharide Mediates Adhesion and Biofilm
      Formation.
AB  - The mold Aspergillus fumigatus causes invasive infection in immunocompromised
      patients. Recently, galactosaminogalactan (GAG), an exopolysaccharide composed of
      galactose and N-acetylgalactosamine (GalNAc), was identified as a virulence
      factor required for biofilm formation. The molecular mechanisms underlying GAG
      biosynthesis and GAG-mediated biofilm formation were unknown. We identified a
      cluster of five coregulated genes that were dysregulated in GAG-deficient mutants
      and whose gene products share functional similarity with proteins that mediate
      the synthesis of the bacterial biofilm exopolysaccharide poly-(beta1-6)-N-acetyl
      D-glucosamine (PNAG). Bioinformatic analyses suggested that the GAG cluster gene
      agd3 encodes a protein containing a deacetylase domain. Because deacetylation of
      N-acetylglucosamine residues is critical for the function of PNAG, we
      investigated the role of GAG deacetylation in fungal biofilm formation. Agd3 was
      found to mediate deacetylation of GalNAc residues within GAG and render the
      polysaccharide polycationic. As with PNAG, deacetylation is required for the
      adherence of GAG to hyphae and for biofilm formation. Growth of the Deltaagd3
      mutant in the presence of culture supernatants of the GAG-deficient Deltauge3
      mutant rescued the biofilm defect of the Deltaagd3 mutant and restored the
      adhesive properties of GAG, suggesting that deacetylation is an extracellular
      process. The GAG biosynthetic gene cluster is present in the genomes of members
      of the Pezizomycotina subphylum of the Ascomycota including a number of plant
      pathogenic fungi and a single basidiomycete species,Trichosporon asahii, likely a
      result of recent horizontal gene transfer. The current study demonstrates that
      the production of cationic, deacetylated exopolysaccharides is a strategy used by
      both fungi and bacteria for biofilm formation. IMPORTANCE: This study sheds light
      on the biosynthetic pathways governing the synthesis of galactosaminogalactan
      (GAG), which plays a key role in A. fumigatus virulence and biofilm formation. We
      find that bacteria and fungi use similar strategies to synthesize adhesive
      biofilm exopolysaccharides. The presence of orthologs of the GAG biosynthetic
      gene clusters in multiple fungi suggests that this exopolysaccharide may also be
      important in the virulence of other fungal pathogens. Further, these studies
      establish a molecular mechanism of adhesion in which GAG interacts via charge
      charge interactions to bind to both fungal hyphae and other substrates. Finally,
      the importance of deacetylation in the synthesis of functional GAG and the
      extracellular localization of this process suggest that inhibition of
      deacetylation may be an attractive target for the development of novel antifungal
      therapies.

PMID- 27048800
TI  - The CpxQ sRNA Negatively Regulates Skp To Prevent Mistargeting of beta-Barrel
      Outer Membrane Proteins into the Cytoplasmic Membrane.
AB  - The promoter most strongly induced upon activation of the Cpx two-component
      envelope stress response is the cpxP promoter. The 3' untranscribed region (UTR)
      of the cpxP transcript is shown to produce a small RNA (sRNA), CpxQ. We
      investigated the role of CpxQ in combating envelope stress. Remarkably, the two
      effectors specified by the transcript are deployed to combat distinct stresses in
      different cellular compartments. CpxP acts in both a regulatory negative-feedback
      loop and as an effector that combats periplasmic protein misfolding. We find that
      CpxQ combats toxicity at the inner membrane (IM) by downregulating the synthesis
      of the periplasmic chaperone Skp. Our data indicate that this regulation prevents
      Skp from inserting beta-barrel outer membrane proteins (OMPs) into the IM, a
      lethal event that likely collapses the proton motive force. Our findings suggest
      that Skp can fold and directly insert OMPs into a lipid bilayer in vivo without
      the aid of the Bam complex. IMPORTANCE: Skp is a well-characterized periplasmic
      chaperone that binds unfolded OMPs. Surprisingly, we find that Skp can catalyze
      the folding and mistargeting of OMPs into the inner membrane without the aid of
      the other cellular proteins that normally assemble OMPs. Several OMPs function as
      diffusion pores. Accordingly, their mistargeting is lethal because it depolarizes
      the inner membrane. We show that the most highly expressed transcript of the Cpx
      stress response produces an sRNA from the 3' UTR, CpxQ, which combats this
      potential toxicity by downregulating Skp production. Defects in OMP assembly
      trigger the sigma(E)response to upregulate factors, including Skp, that promote
      OMP folding. The Cpx response downregulates sigma(E) Our findings reveal that
      this heretofore puzzling hierarchy exists to protect the inner membrane.

PMID- 27048801
TI  - The Importance of First Impressions: Early Events in Mycobacterium tuberculosis
      Infection Influence Outcome.
AB  - Tuberculosis remains a major health threat in much of the world. New vaccines
      against Mycobacterium tuberculosis are essential for preventing infection,
      disease, and transmission. However, the host immune responses that need to be
      induced by an effective vaccine remain unclear. Increasingly, it has become clear
      that early events in infection are of major importance in the eventual outcome of
      the infection. Studying such events in humans is challenging, as they occur
      within the lung and thoracic lymph nodes, and any clinical signs of early
      infection are relatively nonspecific. Nonetheless, clinical studies and animal
      models of tuberculosis have provided new insights into the local events that
      occur in the first few weeks of tuberculosis. Development of an effective vaccine
      requires a clear understanding of the successful (and detrimental) early host
      responses against M. tuberculosis, with the goal to improve upon natural immune
      responses and prevent infection or disease.

PMID- 27048802
TI  - Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of
      Tilapia.
AB  - Tilapia are an important global food source due to their omnivorous diet,
      tolerance for high-density aquaculture, and relative disease resistance. Since
      2009, tilapia aquaculture has been threatened by mass die-offs in farmed fish in
      Israel and Ecuador. Here we report evidence implicating a novel orthomyxo-like
      virus in these outbreaks. The tilapia lake virus (TiLV) has a 10-segment,
      negative-sense RNA genome. The largest segment, segment 1, contains an open
      reading frame with weak sequence homology to the influenza C virus PB1 subunit.
      The other nine segments showed no homology to other viruses but have conserved,
      complementary sequences at their 5' and 3' termini, consistent with the genome
      organization found in other orthomyxoviruses. In situ hybridization indicates
      TiLV replication and transcription at sites of pathology in the liver and central
      nervous system of tilapia with disease. IMPORTANCE: The economic impact of
      worldwide trade in tilapia is estimated at $7.5 billion U.S. dollars (USD)
      annually. The infectious agent implicated in mass tilapia die-offs in two
      continents poses a threat to the global tilapia industry, which not only provides
      inexpensive dietary protein but also is a major employer in the developing world.
      Here we report characterization of the causative agent as a novel orthomyxo-like
      virus, tilapia lake virus (TiLV). We also describe complete genomic and protein
      sequences that will facilitate TiLV detection and containment and enable vaccine
      development.

PMID- 27048803
TI  - Involvement of the Eukaryote-Like Kinase-Phosphatase System and a Protein That
      Interacts with Penicillin-Binding Protein 5 in Emergence of Cephalosporin
      Resistance in Cephalosporin-Sensitive Class A Penicillin-Binding Protein Mutants
      in Enterococcus faecium.
AB  - The intrinsic resistance of Enterococcus faecium to ceftriaxone and cefepime
      (here referred to as "cephalosporins") is reliant on the presence of class A
      penicillin-binding proteins (Pbps) PbpF and PonA. Mutants lacking these Pbps
      exhibit cephalosporin susceptibility that is reversible by exposure to penicillin
      and by selection on cephalosporin-containing medium. We selected two
      cephalosporin-resistant mutants (Cro1 and Cro2) of class A Pbp-deficient E.
      faecium CV598. Genome analysis revealed changes in the serine-threonine kinase
      Stk in Cro1 and a truncation in the associated phosphatase StpA in Cro2 whose
      respective involvements in resistance were confirmed in separate complementation
      experiments. In an additional effort to identify proteins linked to cephalosporin
      resistance, we performed tandem affinity purification using Pbp5 as bait in
      penicillin-exposed E. faecium; these experiments yielded a protein designated
      Pbp5-associated protein (P5AP). Transcription of the P5AP gene was increased
      after exposure to penicillin in wild-type strains and in Cro2 and suppressed in
      Cro2 complemented with the wild-type stpA Transformation of class A Pbp-deficient
      strains with the plasmid-carried P5AP gene conferred cephalosporin resistance.
      These data suggest that Pbp5-associated cephalosporin resistance in E. faecium
      devoid of typical class A Pbps is related to the presence of P5AP, whose
      expression is influenced by the activity of the serine-threonine
      phosphatase/kinase system. IMPORTANCE: beta-Lactam antibiotics remain our most
      effective therapies against susceptible Gram-positive bacteria. The intrinsic
      resistance of Enterococcus faecium to beta-lactams, particularly to
      cephalosporins, therefore represents a major limitation of therapy. Although the
      primary mechanism of resistance to beta-lactams in E. faecium is the presence of
      low-affinity monofunctional transpeptidase (class B) penicillin-binding protein
      Pbp5, the interaction of Pbp5 with other proteins is fundamental to maintain a
      resistant phenotype. The present work identifies a novel, previously
      uncharacterized, protein that interacts with Pbp5, whose expression increases in
      conjunction with stimuli that increase resistance to cephalosporins, and that
      confers increased resistance to cephalosporins when overexpressed. P5AP may
      represent a promising new target, inhibition of which could restore cephalosporin
      susceptibility to E. faecium.

PMID- 27048804
TI  - Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by
      Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut
      Microbiota.
AB  - The gut microbiota is found to be strongly associated with atherosclerosis (AS).
      Resveratrol (RSV) is a natural phytoalexin with anti-AS effects; however, its
      mechanisms of action remain unclear. Therefore, we sought to determine whether
      the anti-AS effects of RSV were related to changes in the gut microbiota. We
      found that RSV attenuated trimethylamine-N-oxide (TMAO)-induced AS in ApoE(-/-)
      mice. Meanwhile, RSV decreased TMAO levels by inhibiting commensal microbial
      trimethylamine (TMA) production via gut microbiota remodeling in mice. Moreover,
      RSV increased levels of the genera Lactobacillus and Bifidobacterium, which
      increased the bile salt hydrolase activity, thereby enhancing bile acid (BA)
      deconjugation and fecal excretion in C57BL/6J and ApoE(-/-) mice. This was
      associated with a decrease in ileal BA content, repression of the enterohepatic
      farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) axis, and
      increased cholesterol 7a-hydroxylase (CYP7A1) expression and hepatic BA
      neosynthesis. An FXR antagonist had the same effect on FGF15 and CYP7A1
      expression as RSV, while an FXR agonist abolished RSV-induced alterations in
      FGF15 and CYP7A1 expression. In mice treated with antibiotics, RSV neither
      decreased TMAO levels nor increased hepatic BA synthesis. Additionally, RSV
      induced inhibition of TMAO-caused AS was also markedly abolished by antibiotics.
      In conclusion, RSV attenuated TMAO-induced AS by decreasing TMAO levels and
      increasing hepatic BA neosynthesis via gut microbiota remodeling, and the BA
      neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis.
      IMPORTANCE: Recently, trimethylamine-N-oxide (TMAO) has been identified as a
      novel and independent risk factor for promoting atherosclerosis (AS) partially
      through inhibiting hepatic bile acid (BA) synthesis. The gut microbiota plays a
      key role in the pathophysiology of TMAO-induced AS. Resveratrol (RSV) is a
      natural phytoalexin with prebiotic benefits. A growing body of evidence supports
      the hypothesis that phenolic phytochemicals with poor bioavailability are
      possibly acting primarily through remodeling of the gut microbiota. The current
      study showed that RSV attenuated TMAO-induced AS by decreasing TMAO levels and
      increasing hepatic BA neosynthesis via gut microbiota remodeling. And RSV-induced
      hepatic BA neosynthesis was partially mediated through downregulating the
      enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These
      results offer new insights into the mechanisms responsible for RSV's anti-AS
      effects and indicate that the gut microbiota may become an interesting target for
      pharmacological or dietary interventions to decrease the risk of developing
      cardiovascular diseases.

PMID- 27048805
TI  - Lateral Gene Transfer in a Heavy Metal-Contaminated-Groundwater Microbial
      Community.
AB  - Unraveling the drivers controlling the response and adaptation of biological
      communities to environmental change, especially anthropogenic activities, is a
      central but poorly understood issue in ecology and evolution. Comparative
      genomics studies suggest that lateral gene transfer (LGT) is a major force
      driving microbial genome evolution, but its role in the evolution of microbial
      communities remains elusive. To delineate the importance of LGT in mediating the
      response of a groundwater microbial community to heavy metal contamination,
      representative Rhodanobacter reference genomes were sequenced and compared to
      shotgun metagenome sequences. 16S rRNA gene-based amplicon sequence analysis
      indicated that Rhodanobacter populations were highly abundant in contaminated
      wells with low pHs and high levels of nitrate and heavy metals but remained rare
      in the uncontaminated wells. Sequence comparisons revealed that multiple
      geochemically important genes, including genes encoding Fe(2+)/Pb(2+) permeases,
      most denitrification enzymes, and cytochrome c553, were native to Rhodanobacter
      and not subjected to LGT. In contrast, the Rhodanobacter pangenome contained a
      recombinational hot spot in which numerous metal resistance genes were subjected
      to LGT and/or duplication. In particular, Co(2+)/Zn(2+)/Cd(2+) efflux and
      mercuric resistance operon genes appeared to be highly mobile within
      Rhodanobacter populations. Evidence of multiple duplications of a mercuric
      resistance operon common to most Rhodanobacter strains was also observed.
      Collectively, our analyses indicated the importance of LGT during the evolution
      of groundwater microbial communities in response to heavy metal contamination,
      and a conceptual model was developed to display such adaptive evolutionary
      processes for explaining the extreme dominance of Rhodanobacter populations in
      the contaminated groundwater microbiome. IMPORTANCE: Lateral gene transfer (LGT),
      along with positive selection and gene duplication, are the three main mechanisms
      that drive adaptive evolution of microbial genomes and communities, but their
      relative importance is unclear. Some recent studies suggested that LGT is a major
      adaptive mechanism for microbial populations in response to changing
      environments, and hence, it could also be critical in shaping microbial community
      structure. However, direct evidence of LGT and its rates in extant natural
      microbial communities in response to changing environments is still lacking. Our
      results presented in this study provide explicit evidence that LGT played a
      crucial role in driving the evolution of a groundwater microbial community in
      response to extreme heavy metal contamination. It appears that acquisition of
      genes critical for survival, growth, and reproduction via LGT is the most rapid
      and effective way to enable microorganisms and associated microbial communities
      to quickly adapt to abrupt harsh environmental stresses.

PMID- 27048806
TI  - Gliotoxin Suppresses Macrophage Immune Function by Subverting
      Phosphatidylinositol 3,4,5-Trisphosphate Homeostasis.
AB  - Aspergillus fumigatus, an opportunistic fungal pathogen, spreads in the
      environment by releasing numerous conidia that are capable of reaching the small
      alveolar airways of mammalian hosts. In otherwise healthy individuals,
      macrophages are responsible for rapidly phagocytosing and eliminating these
      conidia, effectively curbing their germination and consequent invasion of
      pulmonary tissue. However, under some circumstances, the fungus evades phagocyte
      mediated immunity and persists in the respiratory tree. Here, we report thatA.
      fumigatusescapes macrophage recognition by strategically targeting
      phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] metabolism through
      gliotoxin, a potent immunosuppressive mycotoxin. Time-lapse microscopy revealed
      that, in response to the toxin, macrophages cease to ruffle, undergo abrupt
      membrane retraction, and fail to phagocytose large targets effectively. Gliotoxin
      was found to prevent integrin activation and interfere with actin dynamics, both
      of which are instrumental for phagocytosis; similar effects were noted in
      immortalized and primary phagocytes. Detailed studies of the underlying molecular
      mechanisms of toxicity revealed that inhibition of phagocytosis is attributable
      to impaired accumulation of PtdIns(3,4,5)P3and the associated dysregulation of
      downstream effectors, including Rac and/or Cdc42. Strikingly, in response to the
      diacylglycerol mimetic phorbol 12-myristate 13-acetate, gliotoxin-treated
      macrophages reactivate beta integrins, reestablish actin dynamics, and regain
      phagocytic capacity, despite the overt absence of plasmalemmal PtdIns(3,4,5)P3
      Together, our findings identify phosphoinositide metabolism as a critical
      upstream target of gliotoxin and also indicate that increased diacylglycerol
      levels can bypass the requirement for PtdIns(3,4,5)P3signaling during membrane
      ruffling and phagocytosis. IMPORTANCE: Aspergillus fumigatusis the most frequent
      cause of human infections in theAspergillusgenus. In immunocompromised
      populations, invasive aspergillosis (IA) is associated with a mortality rate of
      up to 90%, and current antifungal therapies have failed to prevent or reverse the
      infection. Therefore, a deeper understanding of the interactions betweenA.
      fumigatusand its host is required. In healthy humans, alveolar macrophages can
      ingest and eliminate fungal spores, thus limiting their germination into
      mycotoxin-producing hyphae. Our studies reveal that gliotoxin-the most
      abundantAspergillusmycotoxin-undermines the ability of phagocytes to carry out
      their protective functions. By targeting PtdIns(3,4,5)P3signaling and
      downregulating phagocytic immune defenses, the toxin could also exacerbate
      polymicrobial infections. Notably, we were able to reverse gliotoxin toxicity by
      addition of diacylglycerol analogues, which may provide the basis for therapeutic
      interventions.

PMID- 27048807
TI  - Reduction potential and heme-pocket polarity in low potential cytochrome b5 of
      Giardia intestinalis.
AB  - Although it lacks mitochondria and the ability to synthesize heme, the protozoan
      parasite Giardia intestinalis encodes several heme proteins. This includes four
      members of the cytochrome b5 family, three of which are of similar size to
      mammalian cytochromes b5 but with reduction potentials that are 140 to 180mV
      lower. While no structures have yet been determined for any of these proteins,
      homology modeling points to an increase in heme pocket polarity as a reason for
      their low potentials. To test this we measured the reduction potentials of four
      mutants of Giardia cytochrome b5 isotype-I (gCYTB5-I) in which polar residues at
      two candidate positions (C84, Y51) in the heme pocket were changed to nonpolar
      ones (C84A, C84F; Y51L, Y51F). All mutants were expressed with comparable levels
      of heme incorporation and had UV-visible spectra consistent with low spin bis
      histidyl coordination. These mutations increased the reduction potential by 18 to
      57mV and highlight the influence of C84, which is a residue unique to gCYTB5-I
      and whose mutation to alanine caused the largest increase. The influence of these
      two residues plus that of Y61 reported previously accounts for much of the
      reduction potential difference between gCYTB5-I and microsomal cytochrome b5. A
      complementary triple mutant of the latter with the hydrophilic residues found in
      gCYTB5-I bound heme less effectively but nonetheless had a reduction potential
      that was 135mV lower than wild type.

PMID- 27048808
TI  - This thought is as a death.

PMID- 27048809
TI  - Necrosome core machinery: MLKL.
AB  - In the study of regulated cell death, the rapidly expanding field of regulated
      necrosis, in particular necroptosis, has been drawing much attention. The
      signaling of necroptosis represents a sophisticated form of a death pathway. Anti
      caspase mechanisms (e.g., using inhibitors of caspases, or genetic ablation of
      caspase-8) switch cell fate from apoptosis to necroptosis. The initial
      extracellular death signals regulate RIP1 and RIP3 kinase activation. The RIP3
      associated death complex assembly is necessary and sufficient to initiate
      necroptosis. MLKL was initially identified as an essential mediator of RIP1/RIP3
      kinase-initiated necroptosis. Recent studies on the signal transduction using
      chemical tools and biomarkers support the idea that MLKL is able to make more
      functional sense for the core machinery of the necroptosis death complex, called
      the necrosome, to connect to the necroptosis execution. The experimental data
      available now have pointed that the activated MLKL forms membrane-disrupting
      pores causing membrane leakage, which extends the prototypical concept of
      morphological and biochemical events following necroptosis happening in vivo. The
      key role of MLKL in necroptosis signaling thus sheds light on the logic
      underlying this unique "membrane-explosive" cell death pathway. In this review,
      we provide the general concepts and strategies that underlie signal transduction
      of this form of cell death, and then focus specifically on the role of MLKL in
      necroptosis. 

PMID- 27048810
TI  - Cancer and necroptosis: friend or foe?
AB  - Regulated cell death is one major factor to ensure homoeostasis in multicellular
      organisms. For decades, apoptosis was considered as the sole form of regulated
      cell death, whereas necrosis was believed to be accidental and unregulated. Due
      to this view, research on necrosis was somewhat neglected, especially in the
      field of anti-cancer treatment. However, new interest in necrosis has been
      sparked by the recent discovery of different forms of necrosis that show indeed
      regulated pathways. More and more studies now address the molecular pathways of
      regulated necrosis and its connections within the cellular signaling networks.
      Necroptosis, a subform of regulated necrosis, has so far hardly been focused on
      with regard to a future treatment of cancer patients and may emerge as a novel
      and effective approach to eliminate tumor cells. However, and similar to
      apoptosis, tumor cells can develop resistances against necroptosis to ensure
      their own survival. In this context, new molecules that enhance necroptosis are
      currently being identified to overcome such resistances. This review discusses
      cancer and necroptosis as friends or foes, i.e. the options to exploit
      necroptosis in anti-cancer therapies ("foes"), but also potential limitations
      that may block or actually cause necroptosis to act in a protumoral manner
      ("friends"). The balance between these two possible roles will determine whether
      necroptosis can indeed be used as a promising tool for early diagnosis of tumors,
      prevention of metastasis and anti-cancer treatment.

PMID- 27048811
TI  - Matters of life and death. How neutrophils die or survive along NET release and
      is "NETosis" = necroptosis?
AB  - Neutrophil extracellular trap (NET) formation is a hallmark of many disorders
      that involve neutrophil recruitment, tissue damage, and inflammation. As NET
      formation is often associated with neutrophil death, the term "NETosis" has
      become popular. Upon discovery that neutrophils may survive NET release, apparent
      misnomers, such as "vital NETosis," have been proposed. Meanwhile, it has become
      obvious that certain stimuli can trigger neutrophil necroptosis, a process
      associated with NET-like chromatin release. Here, we discuss the relationship
      between NET release and neutrophil death in view highlighting that many assays
      used in the field do not properly distinguish between the two. An updated
      nomenclature is needed replacing the term "NETosis" to meet the growing variety
      of settings leading to chromatin release with and without neutrophil death.
      Dissecting which triggers of NET release involve which signaling pathway will
      help to define drugable molecular targets that inhibit NET release and/or
      neutrophil necrosis in specific disorders.

PMID- 27048813
TI  - Regulated cell death and adaptive stress responses.
AB  - Eukaryotic cells react to potentially dangerous perturbations of the
      intracellular or extracellular microenvironment by activating rapid
      (transcription-independent) mechanisms that attempt to restore homeostasis. If
      such perturbations persist, cells may still try to cope with stress by activating
      delayed and robust (transcription-dependent) adaptive systems, or they may
      actively engage in cellular suicide. This regulated form of cell death can
      manifest with various morphological, biochemical and immunological correlates,
      and constitutes an ultimate attempt of stressed cells to maintain organismal
      homeostasis. Here, we dissect the general organization of adaptive cellular
      responses to stress, their intimate connection with regulated cell death, and how
      the latter operates for the preservation of organismal homeostasis.

PMID- 27048812
TI  - Generation of small molecules to interfere with regulated necrosis.
AB  - Interference with regulated necrosis for clinical purposes carries broad
      therapeutic relevance and, if successfully achieved, has a potential to
      revolutionize everyday clinical routine. Necrosis was interpreted as something
      that no clinician might ever be able to prevent due to the unregulated nature of
      this form of cell death. However, given our growing understanding of the
      existence of regulated forms of necrosis and the roles of key enzymes of these
      pathways, e.g., kinases, peroxidases, etc., the possibility emerges to identify
      efficient and selective small molecule inhibitors of pathologic necrosis. Here,
      we review the published literature on small molecule inhibition of regulated
      necrosis and provide an outlook on how combination therapy may be most effective
      in treatment of necrosis-associated clinical situations like stroke, myocardial
      infarction, sepsis, cancer and solid organ transplantation.

PMID- 27048814
TI  - Necroptosis-independent signaling by the RIP kinases in inflammation.
AB  - Recent advances have identified a signaling cascade involving receptor
      interacting protein kinase 1 (RIPK1), RIPK3 and the pseudokinase mixed lineage
      kinase domain-like (MLKL) that is crucial for induction of necroptosis, a non
      apoptotic form of cell death. RIPK1-RIPK3-MLKL-mediated necroptosis has been
      attributed to cause many inflammatory diseases through the release of cellular
      damage-associated molecular patterns (DAMPs). In addition to necroptosis,
      emerging evidence suggests that these necroptosis signal adaptors can also
      facilitate inflammation independent of cell death. In particular, the RIP kinases
      can drive NF-kappaB and inflammasome activation independent of cell death. In
      this review, we will discuss recent discoveries that led to this realization and
      present arguments why cell death-independent signaling by the RIP kinases may
      have a more important role in inflammation than necroptosis.

PMID- 27048815
TI  - Inhibition of regulated cell death by cell-penetrating peptides.
AB  - Development of the means to efficiently and continuously renew missing and non
      functional proteins in diseased cells remains a major goal in modern molecular
      medicine. While gene therapy has the potential to achieve this, substantial
      obstacles must be overcome before clinical application can be considered. A
      promising alternative approach is the direct delivery of non-permeant active
      biomolecules, such as oligonucleotides, peptides and proteins, to the affected
      cells with the purpose of ameliorating an advanced disease process. In addition
      to receptor-mediated endocytosis, cell-penetrating peptides are widely used as
      vectors for rapid translocation of conjugated molecules across cell membranes
      into intracellular compartments and the delivery of these therapeutic molecules
      is generally referred to as novel prospective protein therapy. As a broad
      coverage of the enormous amount of published data in this field is unrewarding,
      this review will provide a brief, focused overview of the technology and a
      summary of recent studies of the most commonly used protein transduction domains
      and their potential as therapeutic agents for the treatment of cellular damage
      and the prevention of regulated cell death.

PMID- 27048816
TI  - External and internal triggers of cell death in yeast.
AB  - In recent years, yeast was confirmed as a useful eukaryotic model system to
      decipher the complex mechanisms and networks occurring in higher eukaryotes,
      particularly in mammalian cells, in physiological as well in pathological
      conditions. This article focuses attention on the contribution of yeast in the
      study of a very complex scenario, because of the number and interconnection of
      pathways, represented by cell death. Yeast, although it is a unicellular
      organism, possesses the basal machinery of different kinds of cell death
      occurring in higher eukaryotes, i.e., apoptosis, regulated necrosis and
      autophagy. Here we report the current knowledge concerning the yeast orthologs of
      main mammalian cell death regulators and executors, the role of organelles and
      compartments, and the cellular phenotypes observed in the different forms of cell
      death in response to external and internal triggers. Thanks to the ease of
      genetic manipulation of this microorganism, yeast strains expressing human genes
      that promote or counteract cell death, onset of tumors and neurodegenerative
      diseases have been constructed. The effects on yeast cells of some of these genes
      are also presented. 

PMID- 27048817
TI  - Programmed cell death and clearance of cell corpses in Caenorhabditis elegans.
AB  - Programmed cell death is critical to the development of diverse animal species
      from C. elegans to humans. In C. elegans, the cell death program has three
      genetically distinguishable phases. During the cell suicide phase, the core cell
      death machinery is activated through a protein interaction cascade. This
      activates the caspase CED-3, which promotes numerous pro-apoptotic activities
      including DNA degradation and exposure of the phosphatidylserine "eat me" signal
      on the cell corpse surface. Specification of the cell death fate involves
      transcriptional activation of the cell death initiator EGL-1 or the caspase CED-3
      by coordinated actions of specific transcription factors in distinct cell types.
      In the cell corpse clearance stage, recognition of cell corpses by phagocytes
      triggers several signaling pathways to induce phagocytosis of apoptotic cell
      corpses. Cell corpse-enclosing phagosomes ultimately fuse with lysosomes for
      digestion of phagosomal contents. This article summarizes our current knowledge
      about programmed cell death and clearance of cell corpses in C. elegans.

PMID- 27048818
TI  - The interplay between regulated necrosis and bacterial infection.
AB  - Necrosis has long been considered as a passive event resulting from a cell
      extrinsic stimulus, such as pathogen infection. Recent advances have refined this
      view and it is now well established that necrosis is tightly regulated at the
      cell level. Regulated necrosis can occur in the context of host-pathogen
      interactions, and can either participate in the control of infection or favor it.
      Here, we review the two main pathways implicated so far in bacteria-associated
      regulated necrosis: caspase 1-dependent pyroptosis and RIPK1/RIPK3-dependent
      necroptosis. We present how these pathways are modulated in the context of
      infection by a series of model bacterial pathogens.

PMID- 27048819
TI  - Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping
      pathways of regulated necrosis?
AB  - In contrast to apoptosis and autophagy, necrotic cell death was considered to be
      a random, passive cell death without definable mediators. However, this dogma has
      been challenged by recent developments suggesting that necrotic cell death can
      also be a regulated process. Regulated necrosis includes multiple cell death
      modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and
      mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several
      distinctive executive molecules, particularly residing on the mitochondrial inner
      and outer membrane, amalgamating to form the MPTP have been defined. The c
      subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer
      membrane are considered to be the long sought components that form the MPTP.
      Opening of the MPTP results in loss of mitochondrial inner membrane potential,
      disruption of ATP production, increased ROS production, organelle swelling,
      mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with
      adenine nucleotide translocator and the phosphate carrier are considered to be
      important regulators involved in the opening of MPTP. Increased production of ROS
      can further trigger other necrotic pathways mediated through molecules such as
      PARP1, leading to irreversible cell damage. This review examines the roles of
      PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in
      regulation and integration of key components of signaling pathway to elicit MPTP
      mediated necrosis and ferroptosis is explored. In the context of recent insights,
      the indistinct role of necroptosis signaling in tubular necrosis after ischemic
      kidney injury is scrutinized. We conclude by discussing the participation of p53,
      PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated
      necrosis and ferroptosis in acute kidney injury.

PMID- 27048820
TI  - Mechanisms and consequences of entosis.
AB  - Multiple mechanisms have emerged where the engulfment of whole live cells,
      leading to the formation of what are called 'cell-in-cell' structures, induces
      cell death. Entosis is one such mechanism that drives cell-in-cell formation
      during carcinogenesis and development. Curiously, entotic cells participate
      actively in their own engulfment, by invading into their hosts, and are then
      killed non-cell-autonomously. Here we review the mechanisms of entosis and
      entotic cell death and the consequences of entosis on cell populations.

PMID- 27048823
TI  - Reply by Authors.

PMID- 27048821
TI  - Inflammasomes as polyvalent cell death platforms.
AB  - Inflammasomes are multi-protein platforms that are organized in the cytosol to
      cope with pathogens and cellular stress. The pattern recognition receptors NLRP1,
      NLRP3, NLRC4, AIM2 and Pyrin all assemble canonical platforms for caspase-1
      activation, while caspase-11-dependent inflammasomes respond to intracellular
      Gram-negative pathogens. Inflammasomes are chiefly known for their roles in
      maturation and secretion of the inflammatory cytokines interleukin-(IL)1beta and
      IL18, but they can also induce regulated cell death. Activation of caspases 1 and
      11 in myeloid cells can trigger pyroptosis, a lytic and inflammatory cell death
      mode. Pyroptosis has been implicated in secretion of IL1beta, IL18 and
      intracellular alarmins. Akin to these factors, it may have beneficial roles in
      controlling pathogen replication, but become detrimental in the context of
      chronic autoinflammatory diseases. Inflammasomes are increasingly implicated in
      induction of additional regulated cell death modes such as pyronecrosis and
      apoptosis. In this review, we overview recent advances in inflammasome-associated
      cell death research, illustrating the polyvalent roles of these macromolecular
      platforms in regulated cell death signaling.

PMID- 27048824
TI  - Reply by Authors.

PMID- 27048825
TI  - Re: Long-Term Outcomes of Bladder Neck Reconstruction without Augmentation
      Cystoplasty in Children: G. M. Grimsby, V. Menon, B. J. Schlomer, L. A. Baker, R.
      Adams, P. C. Gargollo and M. A. Jacobs J Urol 2016;195:155-161.

PMID- 27048822
TI  - Mechanisms of ferroptosis.
AB  - Ferroptosis is a non-apoptotic form of cell death that can be triggered by small
      molecules or conditions that inhibit glutathione biosynthesis or the glutathione
      dependent antioxidant enzyme glutathione peroxidase 4 (GPX4). This lethal process
      is defined by the iron-dependent accumulation of lipid reactive oxygen species
      and depletion of plasma membrane polyunsaturated fatty acids. Cancer cells with
      high level RAS-RAF-MEK pathway activity or p53 expression may be sensitized to
      this process. Conversely, a number of small molecule inhibitors of ferroptosis
      have been identified, including ferrostatin-1 and liproxstatin-1, which can block
      pathological cell death events in brain, kidney and other tissues. Recent work
      has identified a number of genes required for ferroptosis, including those
      involved in lipid and amino acid metabolism. Outstanding questions include the
      relationship between ferroptosis and other forms of cell death, and whether
      activation or inhibition of ferroptosis can be exploited to achieve desirable
      therapeutic ends.

PMID- 27048826
TI  - Re: Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in
      Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical
      Prostatectomy?: L. J. Sokoll, Z. Zhang, D. W. Chan, A. C. Reese, T. J.
      Bivalacqua, A. W. Partin and P. C. Walsh J Urol 2016;195:330-336.

PMID- 27048827
TI  - Re: Evaluation and Comparison of Urolithiasis Scoring Systems Used in
      Percutaneous Kidney Stone Surgery: K. Labadie, Z. Okhunov, A. Akhavein, D. M.
      Moreira, J. Moreno-Palacios, M. del Junco, Z. Okeke, V. Bird, A. D. Smith and J.
      Landman J Urol 2015;193:154-159.

PMID- 27048828
TI  - Reply by Authors.

PMID- 27048829
TI  - Re: Letter to the Editor on Structured Withdrawal of Desmopressin in Patients
      with Monosymptomatic Enuresis: M. A. Elkoushy J Urol 2015;193:1446.

PMID- 27048831
TI  - Anti-tumor effects of bemiparin in HepG2 and MIA PaCa-2 cells.
AB  - Recent researches have demonstrated improved survival in oncologic patients
      treated with low molecular weight heparins (LMWHs) which are anticoagulant drugs.
      We evaluated "second generation" LMWH bemiparin and its in vitro anti-tumor
      effects on HepG2 hepatocellular carcinoma and MIA PaCa-2 cancer cells. The aim of
      the study is to investigate anti-cancer mechanism of bemiparin in HepG2 and Mia
      Paca-2 cancer cells. Cytotoxic effects of bemiparin were determined by XTT assay.
      IC50 dose of bemiparin was found to be 200 IU/mL in the 48th hour in the MiaPaCa
      2 cell line and 50 IU/mL in the 48th hour in the HepG2 cell line. CCND1 (cyclin
      D1), CDK4, CDK6, p21, p16, p53, caspase-3, caspase-9, caspase-8, Bcl-2, BID, DR4,
      DR5, FADD, TRADD, Bax, gene mRNA expressions were evaluated by Real-time PCR.
      Real-time PCR analysis showed that CCND1 expression was reduced in HepG2 dose the
      group cells when compared with the control group cells and p53, caspase-3,
      caspase p21, caspase-8 and expressions were increased in the dose group cells
      when compared with the control group cells. CCND1, CDK4 and CDK6 expressions were
      reduced in MIA PaCa-2 dose group cells when compared with the control group cells
      and p53 expression was increased in the dose group cells when compared with the
      control group cells. Other expressions of genes were found statistically
      insignificant both of cell lines. It was found that bemiparin in HepG2 and MIA
      PaCa-2 cells suppressed invasion, migration, and colony formation by using
      matrigel invasion chamber, and colony formation assay, respectively. In
      conclusion, it is thought that bemiparin indicates anti-tumor activity by
      affecting cell cycle arrest, apoptosis, invasion, migration, and colony formation
      on cancer cells.

PMID- 27048830
TI  - CYBA encoding p22(phox), the cytochrome b558 alpha polypeptide: gene structure,
      expression, role and physiopathology.
AB  - P22(phox) is a ubiquitous protein encoded by the CYBA gene located on the long
      arm of chromosome 16 at position 24, containing six exons and spanning 8.5 kb.
      P22(phox) is a critical component of the superoxide-generating nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidases (NOXs). It is associated with
      NOX2 to form cytochrome b558 expressed mainly in phagocytes and responsible for
      the killing of microorganisms when bacterial and fungal infections occur. CYBA
      mutations lead to one of the autosomal recessive forms of chronic granulomatous
      disease (AR22(0)CGD) clinically characterized by recurrent and severe infections
      in early childhood. However, p22(phox) is also the partner of NOX1, NOX3 and
      NOX4, but not NOX5, which are analogs of NOX2, the first identified member of the
      NOX family. P22(phox)-NOX complexes have emerged as one of the most relevant
      sources of reactive oxygen species (ROS) in tissues and cells, and are associated
      with several diseases such as cardiovascular and cerebrovascular diseases. The
      p22(phox)-deficient mouse strain nmf333 has made it possible to highlight the
      role of p22(phox) in the control of inner ear balance in association with NOX3.
      However, the relevance of p22(phox) for NOX3 function remains uncertain because
      AR22(0)CGD patients do not suffer from vestibular dysfunction. Finally, a large
      number of genetic variations of CYBA have been reported, among them the C242T
      polymorphism, which has been extensively studied in association with coronary
      artery and heart diseases, but conflicting results continue to be reported. 

PMID- 27048832
TI  - MicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial
      ovarian cancer.
AB  - AIM: To evaluate the clinical significance of microRNA (miR)-130b-Runt domain
      transcription factor (RUNX3) axis and its effects on oncogenic phenotypes of
      human epithelial ovarian cancer (EOC). METHODS: QRT-PCR was performed to detect
      the expression of miR-130b and RUNX3 mRNA in 100 EOC and 20 normal ovarian
      tissues. The associations between miR-130b and/or RUNX3 expression and various
      clinicopathological features of EOC patients were statistically analyzed. Then,
      the effects of miR-130b-RUNX3 axis on migration and invasion of EOC cells were
      assessed in vitro. RESULTS: miR-130b expression was downregulated, while RUNX3
      mRNA was upregulated, in EOC tissues compared to normal ovarian tissues (both
      P=0.001). Importantly, the expression level of miR-130b in EOC tissues was
      negatively correlated with that of RUNX3 mRNA significantly. Additionally, miR
      130b-low and/or RUNX3-high expression were all closely correlated with advanced
      International Federation of Gynecology and Obstetrics (FIGO) stage (all P<0.05).
      Moreover, overexpression of miR-130b reduced the expression of RUNX3 and
      inhibited cancer cell migration and invasion of EOC cells, whereas knockdown of
      miR-130b increased the expression of RUNX3 and promoted cancer cell migration and
      invasion of EOC cells. After that, the impaired motility of the miR-130b
      overexpression cells was recovered partly by the expression of RUNX3.
      Furthermore, the knockdown of RUNX3 also gave rise to a decrease in cell
      migration and invasion. CONCLUSION: Our data reveal that the dysregulation of miR
      130b-RUNX3 axis may play important roles in EOC development and progression, and
      the loss of miR-130b may contribute to the malignant biological behavior of EOC
      cells via regulating the expression of RUNX3, implying their potentials as
      promising markers for predicting EOC progression and as candidate targets for
      gene therapy.

PMID- 27048833
TI  - Lactobacillus rhamnosus RC007 intended for feed additive: immune-stimulatory
      properties and ameliorating effects on TNBS-induced colitis.
AB  - Lactobacillus rhamnosus RC007 is a potential probiotic bacterium that can exert
      beneficial effects as supplement for animal feed, by improving the immune status
      in healthy host, and by providing therapeutic benefits to infected/inflamed
      animals. The aim of the present work was to evaluate in vivo the beneficial
      properties of L. rhamnosus RC007, intended for animal feed, when administered to
      healthy and trinitro-benzene-sulfonic-acid (TNBS) colitis induced BALB/c mice.
      The administration of L. rhamnosus RC007 to healthy mice during 10 days increased
      the phagocytic activity of peritoneal macrophages and the number of
      immunoglobulin A+ cells in the lamina proper of the small intestine. Significant
      increases of monocyte chemotactic protein 1, interleukin (IL)-10 and tumour
      necrosis factor alpha (TNF-alpha) concentrations, and in the ratio between anti-
      and pro-inflammatory cytokines (IL-10/TNF-alpha) were observed in intestinal
      fluids after administration of bacteria. In the inflammation model, less body
      weight loss, macroscopic and histological damages in the large intestine were
      accompanied by increased IL-10/TNF-alpha ratio in the intestinal fluids of mice
      from the L. rhamnosus-TNBS group when compared to the TNBS group. In a healthy
      host, the oral administration of L. rhamnosus RC007 kept the gut immune system
      stimulated allowing a faster response to noxious stimulus. Mice that received L.
      rhamnosus RC007 also decreased the severity of the intestinal inflammation. 

PMID- 27048834
TI  - Faecalibacterium prausnitzii phylotypes in type two diabetic, obese, and lean
      control subjects.
AB  - Faecalibacterium prausnitzii is one of the main butyrate producers in the healthy
      human gut. Information on its genetic diversity is lacking, although two genetic
      phylotypes have been differentiated. In the present study, F. prausnitzii
      phylotypes were examined in faeces of obese and type two diabetes with similar
      eating behaviour compared to a lean control group. The purpose of the study was
      to analyse if an excessive butyrate production induced by different F.
      prausnitzii phylotypes discriminates between obese developing type two diabetes
      or not. The faecal samples were analysed for the total abundance of F.
      prausnitzii 16S rRNA copies, fragment lengths polymorphism, high resolution melt
      curve analysis (HRM) and the butyryl-CoA:acetate CoA-transferase gene copies and
      melt curve variances. The diabetic group was found to differ significantly from
      the lean control group in the results of qPCR, butyryl-CoA:acetyate CoA
      transferase gene melt curve, and HRM. F. prausnitzii phylotypes differed in obese
      with and without developed diabetes type two. Different phylotypes of F.
      prausnitzii may lead to differences in the inflammatory genesis in the host. F.
      prausnitzii phylotypes may have an influence on developing type two diabetes and
      might also act as starting points for prevention and therapy of obesity
      associated disease. 

PMID- 27048835
TI  - Probiotics and respiratory and gastrointestinal tract infections in Finnish
      military conscripts - a randomised placebo-controlled double-blinded study.
AB  - Military conscripts are susceptible to respiratory and gastrointestinal tract
      infections. In previous studies probiotics have shown potency to reduce upper
      respiratory and gastrointestinal infections. The aim was to study whether
      probiotic intervention has an impact on seasonal occurrence of upper respiratory
      and gastrointestinal infections in two different conscript groups. In a
      randomised, double-blinded, placebo controlled study (https://clinicaltrials.gov
      NCT01651195), a total of 983 healthy adults were enrolled from two intakes of
      conscripts. Conscripts were randomised to receive either a probiotic combination
      of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis ssp. lactis BB12
      (BB12) or a control chewing tablet twice daily for 150 days (recruits) or for 90
      days (reserve officer candidates). Clinical examinations were carried out and
      daily symptom diaries were collected. Outcome measures were the number of days
      with respiratory and gastrointestinal symptoms and symptom incidence, number and
      duration of infection episodes, number of antibiotic treatments received and
      number of days out of service because of the infection. Statistically no
      significant differences were found between the intervention groups either in the
      risk of symptom incidence or duration. However, probiotic intervention was
      associated with reduction of specific respiratory infection symptoms in military
      recruits, but not in reserve officer candidates. Probiotics did not significantly
      reduce overall respiratory and gastrointestinal infection morbidity. 

PMID- 27048836
TI  - Impact of oral consumption of heat-treated Bacteroides xylanisolvens DSM 23964 on
      the level of natural TFalpha-specific antibodies in human adults.
AB  - It is now generally accepted that the human body exists in close synergy with the
      gut microbiome and that this cross-talk plays an essential role in human health
      and disease. One facet from the many interactions between the microbiome and the
      immune system is the induction of natural antibodies to commensal bacterial
      glycans, such as blood group antigens, the alpha-Gal epitope or the Thomsen
      Friedenreich (TFalpha) antigen. Since we have observed that certain species of
      the commensal genus Bacteroides express the TFalpha antigen, we examined whether
      the oral dietary supplementation of a pasteurised Bacteroides xylanisolvens
      strain might be able to enhance the level of natural anti-TFalpha antibodies in
      healthy adults. The data obtained from a double-blind, placebo-controlled study
      involving 140 healthy volunteers and lasting 8 weeks revealed that the oral
      uptake of this strain was indeed able to increase the level of TFalpha-specific
      immunoglobulin M serum antibodies. The effect was dose-dependent but remained -
      at any doses - within the physiological range determined before intervention.
      Furthermore, the effect reverted after stopping the intake. The results support
      the idea of the microbiome inducing the generation of systemic antigen-specific
      antibodies against sugar epitopes. They also demonstrate the possibility to
      modulate essential regulatory or defence processes through dietary
      supplementation of selected commensal bacteria with the aim to assist human
      health. 

PMID- 27048837
TI  - Direct analysis of VLDL by TOF-MS allows rapid definition of Apo E genotypes and
      facilitates characterisation of post translational changes.
AB  - BACKGROUND: Apolipoprotein E (Apo E) is a glycoprotein which acts as a ligand
      facilitating the uptake of lipids. Three common isoforms of Apo E are recognised,
      E2, E3 and E4. E2 and E4 are associated with altered lipid metabolism and
      increased cardiovascular risk. We report a novel variant of Apo E (c.382G>A)
      predicting 110Asp->Asn identified by genotyping, we were prompted to investigate
      this further as the amino acid substitution produced a prospective N
      glycosylation site in this novel variant. METHODS: We present a new rapid
      approach to genotyping Apo E performed by electrospray TOF-MS, on the same sample
      analysed by ultracentrifugation. The analysis can be performed in <10min and
      requires minimal sample volume. Control samples were used to verify the analysis.
      RESULTS: Spectra showed the expected mass for the E3 isoform at 34,237Da, E2 and
      E4 isoforms were identifiable by peaks at -53Da and +53Da respectively. Post
      translational glycosylation of the protein can also be identified. The novel
      isoform had a mass of 34,237Da without evidence of N-glycosylation. No
      significant effect on lipid metabolism was identified. CONCLUSION: The
      electrospray TOF-MS approach potentially provides a rapid alternative method for
      genotyping Apo E and for the investigation of novel isoforms.

PMID- 27048838
TI  - A long-wavelength quantum dot-concentric FRET configuration: characterization and
      application in a multiplexed hybridization assay.
AB  - Quantum dot-based concentric Forster resonance energy transfer (cFRET) is a
      promising modality for the development of multifunctional fluorescent probes for
      bioanalysis and bioimaging. To date, the scope of cFRET has been largely limited
      to a prototypical configuration with a particular combination of quantum dot (QD)
      and fluorescent dyes linked through peptides. Expansion of the scope of cFRET is
      critical for its further development. Here, we expand the scope of cFRET in two
      capacities. First, we design and characterize a new long-wavelength cFRET
      configuration that combines red- and deep-red fluorescent dyes, Alexa Fluor 633
      and Alexa Fluor 680, with an orange-emitting QD. Sequential and competitive
      energy transfer pathways are characterized through a rate analysis, where the
      balance of these rates more strongly favours competitive energy transfer in the
      new long-wavelength configuration versus sequential energy transfer in the
      previous prototypical configuration. Although the new cFRET configuration is more
      susceptible to photobleaching, its superior brightness and longer-wavelength
      excitation and emission provide an order of magnitude higher signal-to-background
      ratios in biological matrices (e.g., serum, blood) than the previous prototypical
      configuration. Second, we demonstrate that an oligonucleotide-linked, long
      wavelength cFRET configuration has energy transfer similar to an analogous
      peptide-linked configuration, where the oligonucleotide-linked cFRET
      configuration can be combined with toehold-mediated strand displacement for the
      multiplexed detection of unlabeled nucleic acid targets as a single vector.
      Overall, this work establishes the general applicability of cFRET and introduces
      new strategies for its bioanalytical application. 

PMID- 27048839
TI  - Preoperative treatment with beta-blockers is associated with elevated
      postoperative mortality and cardiac morbidity in patients with uncomplicated
      hypertension undergoing non-cardiac surgery.

PMID- 27048840
TI  - Low-density lipoprotein cholesterol goals: still not in patients' best interest.

PMID- 27048841
TI  - Revascularization in complex multivessel coronary artery disease after FREEDOM.
      Is there an indication for PCI and drug-eluting stents?
AB  - Diabetes mellitus is a highly prevalent metabolic disorder frequently associated
      with the development of coronary atherosclerosis. Myocardial revascularization
      assumes a central role in the treatment of diabetic patients with coronary artery
      disease. Although coronary artery bypass grafting (CABG) is in principle the
      revascularization modality of choice in diabetic patients with complex,
      multivessel disease, percutaneous coronary interventions (PCI) using new
      generation drug-eluting stents (DES) remain a valuable treatment option for
      properly selected diabetic patients. Defining the appropriate revascularization
      strategy is often a challenging task that requires tailored approaches,
      accounting for individual patient surgical risk, anatomical configurations, and
      the technical feasibility of each procedure in addition to careful judgment of
      the possible benefits and risks inherent to PCI and CABG. Evidence is building
      that advances in DES technology may mitigate at least in part some of the adverse
      vascular effects of diabetes; whether this may translate to PCI outcomes
      comparable with those achieved by CABG is under investigation in randomized
      trials currently underway. This review article summarizes the indications for
      myocardial revascularization across the spectrum of clinical presentations and
      critically discusses current evidence and future perspectives regarding the value
      of each revascularization mode (CABG vs. PCI) in patients with diabetes.

PMID- 27048842
TI  - [Monitoring of pCO2 during ventilation].
AB  - Respiratory insufficiency type 2 (ventilatory failure) is characterized by
      hypercapnia due to alveolar hypoventilation. Therefore, the monitoring of pCO2 is
      essential for diagnostic and surveillance purposes. Various techniques which
      differ in the way of measurement (e.g., invasive/noninvasive,
      continuous/noncontinuous) and their indication are available. Arterial blood gas
      analysis (ABG) as an invasive procedure is the gold standard procedure and is
      mostly used in emergency medicine or intensive care units (ICUs). Another method
      to evaluate pCO2 is capillary blood gas analysis (CBG). Furthermore, endtidal
      pCO2-(PetCO2) and transcutaneous CO2-measurement (PtcCO2) are able to
      continuously and noninvasively monitor pCO2. PetCO2 is mostly used in the field
      of anesthesiology during general anesthesia and is integrated in many
      ventilators, also in ICUs. However, PetCO2 is limited in monitoring pCO2 in
      patients with lung disease and it is only reasonably usable in invasively
      ventilated patients. Transcutaneous pCO2 (PtcCO2) is available as an alternative,
      especially in chronic respiratory failure and to diagnose hypoventilation in
      sleep-related breathing disorders, and it has substantial advantages in these
      indications compared to discontinuous measurements, e.g., blood gas analysis. The
      various methods to monitor pCO2 are generally used synergistically in clinical
      practice. 

PMID- 27048843
TI  - Double standards and arguments for tobacco regulation.

PMID- 27048844
TI  - Replies to Shein, Voigt and Chapman.

PMID- 27048846
TI  - [Erratum to: Venous thrombosis and pulmonary embolism. Updated S2 guidelines on
      diagnostics and therapy].

PMID- 27048845
TI  - ["Why mothers die". Learning from the analysis of anaesthesia-related maternal
      deaths (1985-2013)].
AB  - Every day, more than 800 women die from causes related to pregnancy or
      childbirth. Since 1952 the Confidential Enquiry of Maternal Deaths Reports (CEMD)
      have collected and analysed data on maternal mortality in the United Kingdom and
      Northern Ireland. This publication analyses the CEMD from 1985-2013 regarding
      anaesthesia- and analgesia related maternal deaths during pregnancy or
      peripartum. During this period, there has been a reduction in directly
      anaesthesia-related maternal deaths to 4.3%. Yet, an increase in anaesthesia
      associated maternal deaths has been recorded. The rate of fatal complications
      during obstetric regional anaesthesia doubled in recent years, while the fatality
      risk for obstetric general anaesthesia has decreased. Many of the reported
      maternal deaths could presumably have been avoided. The anaesthesiologist has to
      be familiar with state-of-the-art, guideline-based concepts for anaesthesia
      during pregnancy, childbirth or post partum, especially using tools like
      simulation. Vital sign monitoring after obstetric anaesthesia has to be identical
      to other postoperative monitoring, and Modified Early Warning Scores should be
      used for this purpose. In regional anaesthesia, current standards for hygiene
      have to be adhered to and patients have to be visited after spinal/epidural
      anaesthesia. Interdisciplinary communication and collaboration still have to be
      improved; careful interdisciplinary planning of childbirth in high-risk obstetric
      patients is strongly advised.

PMID- 27048848
TI  - [Importance of partial liver resection in treatment of very early stage
      hepatocellular carcinoma].

PMID- 27048847
TI  - Production and characterization of tearless and non-pungent onion.
AB  - The onion lachrymatory factor (LF) is produced from trans-S-1-propenyl-L-cysteine
      sulfoxide (PRENCSO) through successive reactions catalyzed by alliinase (EC
      4.4.1.4) and lachrymatory factor synthase (LFS), and is responsible for the tear
      inducing-property and the pungency of fresh onions. We developed tearless, non
      pungent onions non-transgenically by irradiating seeds with neon-ion at 20 Gy.
      The bulbs obtained from the irradiated seeds and their offspring bulbs produced
      by selfing were screened by organoleptic assessment of tear-inducing property or
      HPLC analysis of LF production. After repeated screening and seed production by
      selfing, two tearless, non-pungent bulbs were identified in the third generation
      (M3) bulbs. Twenty M4 bulbs obtained from each of them showed no tear-inducing
      property or pungency when evaluated by 20 sensory panelists. The LF production
      levels in these bulbs were approximately 7.5-fold lower than those of the normal
      onion. The low LF production levels were due to reduction in alliinase activity,
      which was a result of low alliinase mRNA expression (less than 1% of that in the
      normal onion) and consequent low amounts of the alliinase protein. These
      tearless, non-pungent onions should be welcomed by all who tear while chopping
      onions and those who work in facilities where fresh onions are processed. 

PMID- 27048849
TI  - Which role for brexpiprazole, a new dopamine D2 partial agonist, in the treatment
      of schizophrenia?

PMID- 27048850
TI  - Impact of additive alcohol and substance use disorders on the mortality of people
      with schizophrenia and mood disorders.

PMID- 27048851
TI  - Growth resumption from stationary phase reveals memory in Escherichia coli
      cultures.
AB  - Frequent changes in nutrient availability often result in repeated cycles of
      bacterial growth and dormancy. The timing of growth resumption can differ among
      isogenic cells and delayed growth resumption can lead to antibiotic tolerant
      persisters. Here we describe a correlation between the timing of entry into
      stationary phase and resuming growth in the next period of cell proliferation. E.
      coli cells can follow a last in first out rule: the last ones to shut down their
      metabolism in the beginning of stationary phase are the first to recover in
      response to nutrients. This memory effect can last for several days in stationary
      phase and is not influenced by environmental changes. We observe that the speed
      and heterogeneity of growth resumption depends on the carbon source. A good
      carbon source (glucose) can promote rapid growth resumption even at low
      concentrations, and is seen to act more like a signal than a growth substrate.
      Heterogeneous growth resumption can protect the population from adverse effect of
      stress, investigated here using heat-shock, because the stress-resilient dormant
      cells are always present. 

PMID- 27048853
TI  - Estimating the production, consumption and export of cannabis: The Dutch case.
AB  - BACKGROUND: Quantifying an illegal phenomenon like a drug market is inherently
      complex due to its hidden nature and the limited availability of reliable
      information. This article presents findings from a recent estimate of the
      production, consumption and export of Dutch cannabis and discusses the
      opportunities provided by, and limitations of, mathematical models for estimating
      the illegal cannabis market. METHODS: The data collection consisted of a
      comprehensive literature study, secondary analyses on data from available
      registrations (2012-2014) and previous studies, and expert opinion. The cannabis
      market was quantified with several mathematical models. The data analysis
      included a Monte Carlo simulation to come to a 95% interval estimate (IE) and a
      sensitivity analysis to identify the most influential indicators. RESULTS: The
      annual production of Dutch cannabis was estimated to be between 171 and 965tons
      (95% IE of 271-613tons). The consumption was estimated to be between 28 and
      119tons, depending on the inclusion or exclusion of non-residents (95% IE of 51
      78tons or 32-49tons respectively). The export was estimated to be between 53 and
      937tons (95% IE of 206-549tons or 231-573tons, respectively). CONCLUSION:
      Mathematical models are valuable tools for the systematic assessment of the size
      of illegal markets and determining the uncertainty inherent in the estimates. The
      estimates required the use of many assumptions and the availability of reliable
      indicators was limited. This uncertainty is reflected in the wide ranges of the
      estimates. The estimates are sensitive to 10 of the 45 indicators. These 10
      account for 86-93% of the variation found. Further research should focus on
      improving the variables and the independence of the mathematical models.

PMID- 27048854
TI  - Talarolutins A-D: Meroterpenoids from an endophytic fungal isolate of Talaromyces
      minioluteus.
AB  - Four meroterpenoids [talarolutins A-D] and one known compound [purpurquinone A]
      were characterized from an endophytic fungal isolate of Talaromyces minioluteus
      (G413), which was obtained from the leaves of the medicinal plant milk thistle
      [Silybum marianum (L.) Gaertn. (Asteraceae)]. The structures of talarolutins A-D
      were determined by the analysis of various NMR and MS techniques. The relative
      and absolute configuration of talarolutin A was determined by X-ray diffraction
      analysis. A combination of NOESY data and comparisons of ECD spectra were
      employed to assign the relative and absolute configuration of the other analogs.
      Talarolutins B-D were tested for cytotoxicity against human prostate carcinoma
      (PC-3) cell line, antimicrobial activity, and induction of quinone reductase; no
      notable bioactivity was observed in any assay. 

PMID- 27048856
TI  - High spatial resolution (1.1 MUm and 20 nm) FTIR polarization contrast imaging
      reveals pre-rupture disorder in damaged tendon.
AB  - Collagen is a major constituent in many life forms; in mammals, collagen appears
      as a component of skin, bone, tendon and cartilage, where it performs critical
      functions. Vibrational spectroscopy methods are excellent for studying the
      structure and function of collagen-containing tissues, as they provide molecular
      insight into composition and organization. The latter is particularly important
      for collagenous materials, given that a key feature is their hierarchical,
      oriented structure, organized from molecular to macroscopic length scales. Here,
      we present the first results of high-resolution FTIR polarization contrast
      imaging, at 1.1 MUm and 20 nm scales, on control and mechanically damaged tendon.
      The spectroscopic data are supported with parallel SEM and correlated AFM
      imaging. Our goal is to explore the changes induced in tendon after the
      application of damaging mechanical stress, and the consequences for the healing
      processes. The results and possibilities for the application of these high
      spatial-resolution FTIR techniques in spectral pathology, and eventually in
      clinical applications, are discussed.

PMID- 27048855
TI  - Association between serum cytokine concentrations and the presence of
      hypertriglyceridemia.
AB  - OBJECTIVE: Hypertriglyceridemia is an established risk factor for coronary-heart
      disease. Inflammatory cytokines are known to be important mediators of
      atherogenesis; however, the relationship between the concentrations of specific
      inflammatory cytokines and the presence of hypertriglyceridemia has not been well
      established. The purpose of this study was to investigate the relationship
      between the serum levels of several pro- and anti-inflammatory cytokines and the
      presence of hypertriglyceridemia. DESIGN AND METHODS: Four hundred and eighty
      four subjects with/without established hypertriglyceridemia were recruited.
      Anthropometric parameters and biochemical analysis (including a full fasting
      lipid profile) were determined. The serum levels of several cytokines and growth
      factors including IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-alpha,
      MCP-1, IFN-gamma, EGF, and VEGF were measured followed by univariate and
      multivariate analyses. RESULTS: Individuals with hypertriglyceridemia had a
      significantly higher body mass index, total-cholesterol and triglyceride,
      compared to the group without hypertriglyceridemia. Serum levels of MCP-1, TNF
      alpha and IL-8 were significantly higher in subjects with hypertriglyceridemia
      [e.g., IL-8 from 7.8ng/L (95% CI: 4.6-18.9) versus 5.7ng/L (95% CI: 3.6-11.9),
      P<0.05]. The multivariate analysis showed that the increased serum concentration
      of TNF-alpha was independently associated with high-density lipoprotein
      cholesterol (HDL-C), while the serum levels of IL-8 and MCP-1 were associated
      with hypertriglyceridemia. CONCLUSION: Subjects with serum triglycerides of
      >=2.25mmol/L had an altered cytokine-profile, particularly with respect to serum
      IL-8, MCP-1 and TNF-alpha, which might partially account for its adverse clinical
      consequences. Further-investigations in a large multi-center setting are
      warranted to unravel the potential functional-importance of these cytokines in
      individuals with hypertriglyceridemia.

PMID- 27048857
TI  - Disaster Olympics: A Model for Resident Education.
AB  - OBJECTIVES: The aim of this study was to describe an educational method teaching
      Disaster Medicine to American Emergency Medicine (EM) physicians and to evaluate
      knowledge attainment using this method. METHODS: This was an observational study
      using a pre-test and a post-test. A full-scale disaster exercise (FSE) was
      conducted at a large academic center with two hospitals in Brooklyn, New York
      (USA). Eighty-two EM residents (physicians in training, post medical school)
      participated in the study. Inclusion criteria for study participation was all EM
      residents training at the State University of New York (SUNY) Downstate at the
      time of the study. There were no exclusion criteria. The exercise was a disaster
      drill designed as "Olympic Games." Participants in the exercise took a pre-test
      and a post-test. The primary outcome of the study was the mean difference between
      pre-test and post-test scores of the study participants using independent sample
      t-tests. Secondary outcomes of the study were percent of critical actions met by
      the residents and the hospitals as measured by direct observation of trained
      study personnel during the exercise. RESULTS: Mean resident post-test scores were
      higher than pre-test scores to a degree that was statistically significant (62%
      versus 53%; P =.002). The residents' performances ranged from 48% to 63% of
      objectives met. The hospitals' performances met 50% to 100% of their objectives.
      CONCLUSION: The use of an Olympic Games format was an effective model for
      disaster education for physicians. The model allowed for evaluation of
      performance and protocols of participants and hospital systems, respectively, and
      may be used objectively to evaluate for areas of improvement. The Disaster
      Olympics drill was found to improve emergency preparedness knowledge in the
      population studied and may constitute a novel and efficacious methodology in
      disaster training. Daniel P , Gist R , Grock A , Kohlhoff S , Roblin P , Arquilla
      B . Disaster Olympics: a model for resident education. Prehosp Disaster Med.
      2016;31(3):237-241.

PMID- 27048858
TI  - Frailty Is Associated with Disability and Recent Hospitalization in Community
      Dwelling Elderly: The Coyoacan Cohort.
AB  - BACKGROUND: The phenotype of frailty proposed by Fried et al has shown to predict
      several adverse health-related outcomes in elderly populations worldwide;
      however, the description of such associations in Latin America is still scarce.
      OBJECTIVE: To describe the association between frailty and recent
      hospitalization, disability for basic (ADL) and instrumental activities of daily
      living (IADL). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 1,124
      community-dwelling adults aged 70 and older participating in the Coyoacan cohort.
      MEASUREMENTS: Frailty was defined by the presence of at least three of the
      following criteria: weight loss, exhaustion, low physical activity, slowness, and
      weakness. Multiple regression analyses were used to test the association between
      frailty and the outcomes of interest, adjusting for potential confounders.
      RESULTS: Mean age was 78.2 (SD +/-6.1) years. Prevalence of frailty was 14.1%.
      Adjusted multivariate models showed that frail status was associated with ADL
      disability (OR 3.06, 95%CI 1.52-6.17), IADL disability (OR 17.02, 95%CI 6.16
      47.01), and recent hospitalization (OR 3.21, 95%CI 1.31-7.8). CONCLUSION: Among
      Mexican community-dwelling elderly, frailty is associated with ADL and IADL
      disability as well as with recent hospitalizations. Moreover, frailty's
      prevalence in this population appears to be greater compared to what has been
      reported elsewhere. Social and cultural traits should be further studied as
      correlates of frailty in diverse populations.

PMID- 27048859
TI  - Comparison of Near-Infrared Spectroscopy and Bioelectrical Impedance Analysis for
      the Assessment of Body Composition in the Frail Elderly.
AB  - BACKGROUND: Body composition is an important component of health related fitness.
      Near-infrared spectroscopy (NIRS) is a non-invasive, simple and rapid method of
      assessing body fat percentage. However, it is unknown whether NIRS can accurately
      estimate FFM in community-dwelling frail elderly. OBJECTIVES: This study aimed to
      compare NIRS with bioelectrical impedance analysis (BIA) in FFM measurement.
      DESIGN: Cross-sectional study. SETTING: Shizuoka, Japan. PARTICIPANTS: The study
      population comprised 53 community-dwelling frail elderly (15 men, 38 women; mean
      age 84.8+/-6.4 years; body mass index 19.7+/-3.5 kg/m2). MEASUREMENT: FFM and
      percentage fat mass (%FM) were estimated using a NIRS device at two sites (biceps
      and calf) and compared to body composition measured by BIA. Simple linear
      regression and Bland-Altman analyses were used to determine agreement between the
      methods. RESULTS: FFM determined by BIA highly correlated with that determined by
      NIRS at both the biceps and calf (r=0.92 for both; p<0.001). The correlation
      coefficients for %FM estimated by NIRS were slightly lower (r=0.70 for biceps;
      r=0.66 for calf). In NIRS assessments, systematic biases were found for %FM but
      not for FFM. CONCLUSION: NIRS has significant potential for body composition
      analysis. Further comparative and longitudinal studies need to be conducted using
      an agreed reference analysis method to find a simple and more suitable method
      that can be applied among the community-dwelling frail elderly.

PMID- 27048860
TI  - Facilitating Frailty Identification: Comparison of Two Methods among Community
      Dwelling Order Adults.
AB  - BACKGROUND: Frailty is characterized by increased vulnerability for adverse
      events such as falls, fractures, placement, and death. Several frailty models
      have been developed, including the widely accepted Frailty Phenotype. However,
      the Frailty Phenotype can be difficult to apply in clinical practice.
      Alternatively, the Clinical Frailty Scale has been proposed based on its
      simplicity. To date, the Clinical Frailty Scale has not been validated against
      the Frailty Phenotype. OBJECTIVE: We aimed to test the inter-rater reliability of
      the Clinical Frailty Scale and its agreement with the Frailty Phenotype in
      frailty identification. DESIGN: Cross-sectional study. SETTING: Retirement
      community in London, Ontario, Canada. PARTICIPANTS: One hundred and four
      community-dwelling older adults (age >=75 years). MEASUREMENTS: Participants were
      first classified using the Frailty Phenotype criteria as not frail, pre-frail or
      frail. Subsequently, two clinicians blinded to the first assessment, determined
      frailty status using the Clinical Frailty Scale. Differences between assessments
      were resolved by consensus. Inter-rater reliability was assessed using kappa
      statistics. Spearman Rho correlation coefficients evaluated the concurrent
      validity of the Clinical Frailty Scale against Frailty Phenotype components.
      RESULTS: Analysis with kappa statistic showed substantial agreement between
      raters in applying the Clinical Frailty Scale to the sample (kappaw= 0.76, 95% CI
      0.68, 0.84). The Clinical Frailty Scale scores also positively correlated with an
      increasing number of Frailty Phenotype components (rho=0.69, p<0.01). CONCLUSION:
      The Clinical Frailty Scale is reliable and comparable to the Frailty Phenotype in
      identifying frailty in community-dwelling older adults with the advantage of
      being easy to administer in clinical settings. Reliable tools to identify frailty
      in community-dwelling older adults may help provide timely interventions to
      ameliorate risk of adverse events.

PMID- 27048861
TI  - Impact of Different Diagnostic Criteria on the Prevalence of Sarcopenia in an
      Acute Care Geriatric Ward.
AB  - BACKGROUND: Sarcopenia is probably an important causal factor for functional
      decline in acutely ill hospitalized geriatric patients. Low skeletal muscle mass,
      low gait speed and low grip strength are hallmarks of diagnosing sarcopenia.
      However there are many different diagnostic criteria to assess sarcopenia.
      OBJECTIVES: In this study the influence of different criteria for sarcopenia was
      studied on sarcopenia prevalence in geriatric patients admitted to an acute care
      hospital. DESIGN: Cross sectional study design. SETTING: A geriatric ward of a
      large Dutch hospital. PARTICIPANTS: Geriatric patients. MEASUREMENTS: Skeletal
      muscle mass measured using bio impedance analysis (BIA), gait speed using the 4
      meter walking test and grip strength. The sarcopenia prevalence was investigated
      according to criteria of: muscle mass, grip strength, the European Working Group
      on Sarcopenia in Elderly People, the International Working Group on Sarcopenia
      and the Special Interest Group of Society of Sarcopenia, Cachexia and Wasting
      Disorders. RESULTS: 85 geriatric patients were included (61 women). Applying the
      17 different criteria, the sarcopenia prevalence varied from 26-75% for women and
      from 42-100% for men. Comparing the Janssen calculation with the Maltron
      calculation sarcopenia prevalence ranged from respectively 26-67% and 67-70% for
      women and from 42-71% and 75-100% for men. Almost all patients (96%) had a low
      gait speed. CONCLUSIONS: Sarcopenia is highly prevalent in an acute hospitalized
      geriatric population, although the prevalence varies widely depending on the
      diagnostic criteria applied. A prospective study is needed to discover which
      criteria of sarcopenia can predict best adverse outcomes.

PMID- 27048862
TI  - Considerations for the Perioperative Care of Elderly and Frail Patients.
AB  - The number of elderly patients undergoing anesthesia is increasing. At the same
      time aging is associated with decreased functional reserve of all major organ
      systems and an increase in comorbid conditions, requiring a comprehensive
      perioperative evaluation to minimize morbidity and mortality. The preoperative
      assessment should focus on the risk/benefit analysis vis-a-vis the proposed
      intervention, allowing the practitioner to adapt surgical and anesthetic care, as
      well optimize health and functional status. In addition to the usual evaluation
      for cardiac and pulmonary risk, the preoperative assessment in the older patient
      should also address the risk of postoperative cognitive dysfunction and delirium.
      'Do-not-resuscitate' orders must be clarified with the patients or substitute
      decision maker. Studies have not been able to clearly show the superiority of one
      anesthetic approach for the geriatric patient, although there are probably
      advantages to using regional anesthetic techniques. Overall the patient's
      preoperative functional status along with the proposed intervention is the
      primary determinants of the patient's long term functional outcome and wellbeing.
      The elderly patient may be at his most vulnerable during the postoperative phase,
      and a relatively high frequency of adverse events in the elderly, including
      respiratory insufficiency, myocardial and cerebrovascular ischemia, renal
      failure, infectious complications as well as delirium and postoperative cognitive
      dysfunction have been observed. Perioperative interventions should target
      modifiable risk factors and the avoidance of even minor complications with an
      ultimate goal of improving long-term outcome. 

PMID- 27048863
TI  - The Impact of Frailty on Post-Acute Rehabilitation Outcomes in Older Adults.
AB  - Objective, Design, Measurements: We assessed the correlations of the Frailty
      Instrument for primary care of the Survey of Health, Ageing and Retirement in
      Europe (SHARE-FI on admission: non-frail, pre-frail, frail) with the outcomes of
      a Short-term Post-Acute Rehabilitative Care programme (N=172 admissions over one
      year period, 95 of which were frail). RESULTS: SHARE-FI correlated with age (non
      frail: mean 79.2 years; frail: 83.6; P<0.001). Adjusting for age, SHARE-FI
      correlated with longer length of stay (non-frail: median 30 days; frail: 42;
      P=0.047), higher rate of emergency transfer to acute hospital (non-frail: 2.4%;
      frail: 21.1%; P=0.004), and lower home discharge rate (non-frail: 97.6%; frail:
      81.9%; P=0.009). While frailty correlated with more disability on admission and
      discharge, there was no statistically significant difference in Barthel Index
      (BI) improvement across frailty categories (all groups had median BI improvement
      of >=2 points, P=0.247). CONCLUSION: The post-acute rehabilitation of the frail
      is worthwhile but requires more time and access to acute hospital facilities.

PMID- 27048864
TI  - Proxy-Reports in the Ascertainment of Disability Prevalence with American
      Community Survey Data.
AB  - BACKGROUND: Population estimates on disability prevalence inform policy makers
      and public health professionals. Understanding how factors capable of affecting
      measurement (e.g., proxy-report) vary in the population is important for
      establishing level of confidence in sample-derived population estimates.
      OBJECTIVES: To establish how use of proxy-reports varies by six disability types
      stratified by sex, race-ethnicity, and age group. Specific aim is achieved by
      investigating the number of proxy-reports used amongst the disable population.
      DESIGN: Cross-sectional study using American Community Survey (ACS) Public Use
      Microdata Sample (PUMS) 3-year file collected during 2009-2011 survey period.
      SETTING: Community-dwelling population in continental United States (US).
      PARTICIPANTS: The unweighted count of 6,003,183 individuals in the microdata are
      said to represent about 193,277,485 individuals in the continental US population.
      MEASUREMENTS: Stratified disability period estimates are computed. Amongst the
      disable: the number of proxy-reports; allocations; and Person Inflation Ratios
      (PRIs) are presented by disability type. RESULTS: Half of all the reported
      disabilities are derived through the use of proxy-report. In addition, high rates
      of item-allocation and PRIs are generally found in race-ethnic minorities. Proxy
      report use and PRIs are lower for those aged > 65-but not allocation rates.
      CONCLUSIONS: Although use of proxy report in the ascertainment of disability
      varies in complex ways, data suggest prevalence of proxy reports is lowest
      amongst Non-Latino-Black females ages 21 to 64. Efforts toward providing
      clinicians with high quality descriptive epidemiology should continue as a
      reliable thermometer for measuring disability in the population is needed.

PMID- 27048865
TI  - How Do Community Physical and Occupational Therapists Classify Frailty? A pilot
      Study.
AB  - BACKGROUND: Frailty is a complex geriatric syndrome that is often difficult to
      diagnose, especially by healthcare professionals working in the community.
      Objectives, Measurements: This study examined how physical and occupational
      therapists classified community-dwelling clients using categories of 'nonfrail',
      'prefrail' or 'frail' as compared to measurements of established frailty criteria
      from the Cardiovascular Health Study frailty index (CHSfi). RESULTS: Results
      indicate that community therapists underestimate frailty in comparison to the
      CHSfi. Therapists' classification of frailty suggested their perceptions of
      frailty may not only relate to client's functional capacity, but the context in
      which the client receives care. CONCLUSION: A multi-dimensional approach is
      required to capture all aspects of frailty across the healthcare continuum that
      accounts for how the client thrives within their personal environment.

PMID- 27048866
TI  - Combined Population Dynamics and Entropy Modelling Supports Patient
      Stratification in Chronic Myeloid Leukemia.
AB  - Modelling the parameters of multistep carcinogenesis is key for a better
      understanding of cancer progression, biomarker identification and the design of
      individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for
      hierarchical disease evolution we show that combined population dynamic modelling
      and CML patient biopsy genomic analysis enables patient stratification at
      unprecedented resolution. Linking CD34(+) similarity as a disease progression
      marker to patient-derived gene expression entropy separated established CML
      progression stages and uncovered additional heterogeneity within disease stages.
      Importantly, our patient data informed model enables quantitative approximation
      of individual patients' disease history within chronic phase (CP) and
      significantly separates "early" from "late" CP. Our findings provide a novel
      rationale for personalized and genome-informed disease progression risk
      assessment that is independent and complementary to conventional measures of CML
      disease burden and prognosis. 

PMID- 27048867
TI  - Effect of Single Layer Centrifugation on reactive oxygen species and sperm
      mitochondrial membrane potential in cooled stallion semen.
AB  - Additional means are needed for evaluating the quality of stallion spermatozoa in
      semen doses for AI. Mitochondrial membrane potential (DeltaPsim) has been linked
      to fertility in some species, but is rarely used in the evaluation of cooled
      stallion semen; metabolic activity may be associated with reactive oxygen species
      production (ROS). In the present study, DeltaPsim and ROS production were
      measured in doses of cooled stallion semen. The effect of colloid centrifugation
      on these parameters was also investigated. In this case, colloid centrifugation
      involves centrifuging a sperm sample through a silane-coated silica colloid
      formulation to retrieve the most robust spermatozoa. High and low DeltaPsim in
      cooled stallion semen varied between stallions and between ejaculates, but was
      not affected by single-layer centrifugation (SLC). The SLC-selected spermatozoa
      produced significantly less hydrogen peroxide than controls (P < 0.001), which
      could explain the increased longevity and retention of fertilising capacity seen
      in previous studies. For SLC samples, DeltaPsim was positively associated with
      viable spermatozoa that were not producing reactive oxygen species (r = 0.49; P <
      0.001) and negatively associated with ROS production (for superoxide: r = -0.4, P
      < 0.01; for hydrogen peroxide: r = -0.39, P < 0.05). There was no clear
      association between DeltaPsim and ROS production in control samples.

PMID- 27048868
TI  - Multi-centre Raman spectral mapping of oesophageal cancer tissues: a study to
      assess system transferability.
AB  - The potential for Raman spectroscopy to provide early and improved diagnosis on a
      wide range of tissue and biopsy samples in situ is well documented. The standard
      histopathology diagnostic methods of reviewing H&E and/or immunohistochemical
      (IHC) stained tissue sections provides valuable clinical information, but
      requires both logistics (review, analysis and interpretation by an expert) and
      costly processing and reagents. Vibrational spectroscopy offers a complimentary
      diagnostic tool providing specific and multiplexed information relating to
      molecular structure and composition, but is not yet used to a significant extent
      in a clinical setting. One of the challenges for clinical implementation is that
      each Raman spectrometer system will have different characteristics and therefore
      spectra are not readily compatible between systems. This is essential for
      clinical implementation where classification models are used to compare measured
      biochemical or tissue spectra against a library training dataset. In this study,
      we demonstrate the development and validation of a classification model to
      discriminate between adenocarcinoma (AC) and non-cancerous intraepithelial
      metaplasia (IM) oesophageal tissue samples, measured on three different Raman
      instruments across three different locations. Spectra were corrected using system
      transfer spectral correction algorithms including wavenumber shift (offset)
      correction, instrument response correction and baseline removal. The results from
      this study indicate that the combined correction methods do minimize the
      instrument and sample quality variations within and between the instrument sites.
      However, more tissue samples of varying pathology states and greater tissue area
      coverage (per sample) are needed to properly assess the ability of Raman
      spectroscopy and system transferability algorithms over multiple instrument
      sites.

PMID- 27048869
TI  - ICU Telemedicine Comanagement Methods and Length of Stay.
AB  - BACKGROUND: Studies have identified processes that are associated with more
      favorable length of stay (LOS) outcomes when an ICU telemedicine program is
      implemented. Despite these studies, the relation of the acceptance of ICU
      telemedicine management services by individual ICUs to LOS outcomes is unknown.
      METHODS: This is a single ICU telemedicine center study that compares LOS
      outcomes among three groups of intensivist-staffed mixed medical-surgical ICUs
      that used alternative comanagement strategies. The proportion of provider orders
      recorded by an ICU telemedicine provider to all recorded orders was compared
      among ICUs that used a monitor and notify comanagement approach, a direct
      intervention with timely notification process, and ICUs that used a mix of these
      two approaches. The primary outcome was acuity-adjusted hospital LOS. RESULTS:
      ICUs that used the direct intervention with timely notification strategy had a
      significantly larger proportion of provider orders recorded by ICU telemedicine
      physicians than the mixed methods of comanagement group, which had a larger
      proportion than ICUs that used the monitor and notify method (P < .001). Acuity
      adjusted hospital LOS was significantly lower for the direct intervention with
      timely notification comanagement strategy (0.68; 0.65-0.70) compared with the
      mixed methods group (0.70 [0.69-0.72]; P = .01), which was significantly lower
      than the monitor and notify group (0.83 [0.80-0.86]; P < .001). CONCLUSIONS:
      Direct intervention with timely notification strategies of ICU telemedicine
      comanagement were associated with shorter LOS outcomes than monitor and notify
      comanagement strategies.

PMID- 27048870
TI  - Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in
      Pulmonary Arterial Hypertension: A Meta-analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH)
      specific therapy for PAH pooled PAH-specific combination therapy and monotherapy.
      This flaw may threaten the authenticity of their findings. METHODS: PubMed,
      Embase, and the Cochrane Library were searched for randomized controlled trials
      that evaluated any PAH-specific medications in the treatment of PAH. We
      calculated ORs with 95% CIs for dichotomous data and standardized mean
      differences for continuous data. RESULTS: In total, 35 randomized controlled
      trials involving 6,702 patients were included. In monotherapy vs
      placebo/conventional therapy, significance was obtained in mortality reduction
      (OR, 0.50 [95% CI, 0.33 to 0.76]; P = .001), 6-min walk test (mean difference,
      31.10 m [95% CI, 25.40 to 36.80]; P < .00001), New York Heart Association/World
      Health Organization functional class (OR, 2.48 [95% CI, 1.51 to 4.07]; P =
      .0003), and hemodynamic status based on mean pulmonary artery pressure, pulmonary
      vascular resistance, cardiac index, and incidence of withdrawal due to adverse
      effects. In combination therapy vs monotherapy, significance was reached for the
      6-min walk test (mean difference, 19.96 m [95% CI, 15.35 to 24.57]; P < .00001),
      functional class (OR, 1.65 [95% CI, 1.20 to 2.28]; P = .002), hemodynamic status,
      and incidence of withdrawal due to adverse effects (OR, 2.01 [95% CI, 1.54 to
      2.61]; P < .00001) but not for mortality reduction (OR, 0.98 [95% CI, 0.57 to
      1.68]; P = .94). CONCLUSIONS: Our meta-analysis revealed that PAH-specific
      monotherapy could improve mortality, exercise capacity, functional class, and
      hemodynamic status compared with placebo or conventional therapy. However,
      combination therapy could further improve exercise capacity, functional class,
      and hemodynamic status compared with monotherapy, but it had no proven effect on
      mortality. Combination therapy had a much higher incidence of withdrawal due to
      adverse effects than monotherapy.

PMID- 27048871
TI  - Oxygen With Cold Bubble Humidification Is No Better Than Dry Oxygen in Preventing
      Mucus Dehydration, Decreased Mucociliary Clearance, and Decline in Pulmonary
      Function.
AB  - BACKGROUND: Little is known about the effects of long-term nasal low-flow oxygen
      (NLFO) on mucus and symptoms and how this variable is affected by dry or cold
      humidified gas. The aim of this study was to investigate the effects of dry-NLFO
      and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus
      properties, inflammation, and symptoms in subjects with chronic hypoxemia
      requiring long-term domiciliary oxygen therapy. METHODS: Eighteen subjects (mean
      age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive
      dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline,
      12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the
      saccharin transit test, mucus contact angle (surface tension), inflammation
      (cells and cytokine concentration in nasal lavage), and symptoms according to the
      Sino-Nasal Outcome Test-20. RESULTS: Nasal MCC decreased significantly (40%
      longer saccharin transit times) and similarly in both groups over the study
      period. There was a significant association between impaired nasal MCC and
      decline in lung function. Nasal lavage revealed an increased proportion of
      macrophages, interleukin-8, and epidermal growth factor concentrations with
      decreased interleukin-10 during the study. No changes in the proportion of
      ciliated cells or contact angle were observed. Coughing and sleep symptoms
      decreased similarly in both groups. There were no outcome differences comparing
      dry vs cold bubble humidified NLFO. CONCLUSIONS: In subjects receiving chronic
      NLFO, cold bubble humidification does not adequately humidify inspired oxygen to
      prevent deterioration of MCC, mucus hydration, and pulmonary function. The
      unheated bubble humidification performed no better than no humidification. TRIAL
      REGISTRY: ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov.

PMID- 27048873
TI  - Waist circumference distribution in Colombian schoolchildren and adolescents: The
      FUPRECOL Study.
AB  - OBJECTIVE: This study was intended to establish the percentile distribution of
      waist circumference in schoolchildren from Bogota, Colombia, participating in the
      FUPRECOL Study. METHODS: A cross-sectional study conducted in 3,005 children and
      2,916 adolescents aged 9 to 17.9 years. Height, weight, waist circumference, hip
      circumference, and self-assessed sexual maturity status were recorded.
      Percentiles (3(rd), 10(th), 25(th), 50(th), 75(th), 90(th), and 97(th)) and
      smoothed sex- and age-specific curves were calculated, and the waist
      circumference values found were compared to international references from other
      ethnic populations. RESULTS: Fifty-seven percent of the overall population
      (n=5,921) were females (mean age, 12.7+/-2.3 years). In most age groups, waist
      circumference was greater in boys as compared to girls. The increase between the
      50(th) and 97(th) percentiles by age was 15.7cm in boys aged 9 to 9.9 years and
      16.0cm in girls aged 11-11.9 years. Comparison of our study results, by age group
      and sex, to international references showed that our 50(th) percentile was lower
      than reported in Peru and the UK except for studies in India, Venezuela (Merida),
      US, and Spain was higher. CONCLUSIONS: Age- and sex-specific percentiles of waist
      circumference obtained from children and adolescents from Bogota, Colombia, are
      reported. They may be used as a reference both for nutritional assessment and for
      predicting cardiovascular risks at early ages.

PMID- 27048874
TI  - Location and deprivation are important influencers of physical activity in
      primary care populations.
AB  - OBJECTIVES: To investigate the physical activity of adults attending primary care
      services in the Republic of Ireland and to determine whether the location
      (urban/rural) and deprivation of the primary care centre influenced physical
      activity. STUDY DESIGN: Cross sectional study. METHODS: Stratified random
      sampling based on urban/rural location and deprivation was used to identify three
      primary care centres from a list of established primary care teams in the
      Leinster region. The International Physical Activity Questionnaire (IPAQ) was
      used to collate data on physical activity category (low/moderate/high), total
      weekly activity (MET-minutes/week) and weekly walking (MET-minutes/week) of
      participants. RESULTS: Data from 885 participants with a median age of 39 years
      (IQR 31-53) were analysed. There were significant differences in physical
      activity between the primary care areas (P < 0.001). Rural mixed deprivation
      participants were the least active with almost 60% of this group (59.4%, n = 177)
      classified as inactive (535 median MET-minutes/week, IQR 132-1197). Urban
      deprived participants were the most active (low active 37.6%, n = 111, 975 median
      MET-minutes/week, IQR 445-1933). Upon adjustment for multiple factors, rural
      participants (OR = 2.81, 95% CI 1.97-4.01), urban non-deprived participants (OR =
      1.61, 95% CI 1.08-2.39), females (OR = 1.66, 95% CI 1.23-2.23) and older adults
      (OR = 1.01, 95% CI 1.00-1.02) were more likely to be categorised as low active.
      Overall 47.2% (n = 418) of all participants were classified within the low
      physical activity category. CONCLUSIONS: Significant disparities exist in the
      physical activity levels of primary care populations. This has important
      implications for the funding and planning of physical activity interventions.

PMID- 27048872
TI  - GATA3 induces human T-cell commitment by restraining Notch activity and
      repressing NK-cell fate.
AB  - The gradual reprogramming of haematopoietic precursors into the T-cell fate is
      characterized by at least two sequential developmental stages. Following Notch1
      dependent T-cell lineage specification during which the first T-cell lineage
      genes are expressed and myeloid and dendritic cell potential is lost, T-cell
      specific transcription factors subsequently induce T-cell commitment by
      repressing residual natural killer (NK)-cell potential. How these processes are
      regulated in human is poorly understood, especially since efficient T-cell
      lineage commitment requires a reduction in Notch signalling activity following T
      cell specification. Here, we show that GATA3, in contrast to TCF1, controls human
      T-cell lineage commitment through direct regulation of three distinct processes:
      repression of NK-cell fate, upregulation of T-cell lineage genes to promote
      further differentiation and restraint of Notch activity. Repression of the Notch1
      target gene DTX1 hereby is essential to prevent NK-cell differentiation. Thus,
      GATA3-mediated positive and negative feedback mechanisms control human T-cell
      lineage commitment. 

PMID- 27048875
TI  - Phenylene vinylene macrocycles as artificial transmembrane transporters.
AB  - A series of rigid phenylene vinylene macrocycles and phenylene ethynylene
      macrocycles with various substituents have been investigated as transmembrane ion
      channels. The length and polarity of the substituents have a significant effect
      on the ion channel formation and the mass transport efficiency. Macrocycles with
      strong aggregation facilitate ion passage across lipid bilayers. 

PMID- 27048876
TI  - Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk
      alleles in Indian population.
AB  - HLA-Cw6 is one of the most associated alleles in psoriasis. Recently, Late
      Cornified Envelop 3 (LCE3) genes were identified as a susceptibility factor for
      psoriasis. Some population showed epistatic interaction of LCE3 risk variants
      with HLA-Cw6, while some population failed to show any association. We determined
      the associations of a 32.2 kb deletion comprising LCE3C-3B genes and three SNPs
      (rs1886734, rs4112788; rs7516108) at the LCE3 gene cluster among the psoriasis
      patients in India. All three SNPs at the LCE3 gene cluster failed to show any
      association. In contrary, for patients with HLA-Cw6 allele, all three SNPs and
      the LCE3C-3B deletion showed significant associations. While, all five LCE3 genes
      were upregulated in psoriatic skin, only LCE3A showed significant overexpression
      with homozygous risk genotype compared to the non-risk genotype. LCE3B also
      showed significant overexpression in patients with HLA-Cw6 allele. Moreover,
      LCE3A showed significantly higher expression in patients bearing homozygous risk
      genotype in presence of HLA-Cw6 allele but not in those having non-risk genotype,
      demonstrating the combined effect of HLA-Cw6 allele and risk associated genotype
      near LCE3A gene. Integration of genetic and gene expression data thus allowed us
      to identify the actual disease variants at the LCE3 cluster among the psoriasis
      patients in India. 

PMID- 27048877
TI  - Rapid, noninvasive quantitation of skin disease in systemic sclerosis using
      optical coherence elastography.
AB  - Systemic sclerosis (SSc) is a connective tissue disease that results in excessive
      accumulation of collagen in the skin and internal organs. Overall, SSc has a rare
      morbidity (276 cases per million adults in the United States), but has a 10-year
      survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is
      assessed by palpation on 17 sites on the body. However, the mRSS assessed score
      is subjective and may be influenced by the experience of the rheumatologists. In
      addition, the inherent elasticity of skin may bias the mRSS assessment in the
      early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a
      rapidly emerging technique, which can assess mechanical contrast in tissues with
      micrometer spatial resolution. In this work, the OCE technique is applied to
      assess the mechanical properties of skin in both control and bleomycin (BLM)
      induced SSc-like disease noninvasively. Young's modulus of the BLM-SSc skin was
      found be significantly higher than that of normal skin, in both the in vivo and
      in vitro studies (p<0.05 p<0.05 ). Thus, OCE is able to differentiate healthy and
      fibrotic skin using mechanical contrast. It is a promising new technology for
      quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.

PMID- 27048878
TI  - Nuclear receptor TLX inhibits TGF-beta signaling in glioblastoma.
AB  - TLX (also called NR2E1) is an orphan nuclear receptor that maintains stemness of
      neuronal stem cells. TLX is highly expressed in the most malignant form of
      glioma, glioblastoma multiforme (GBM), and is important for the proliferation and
      maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor
      beta (TGF-beta) is a cytokine regulating many different cellular processes such
      as differentiation, migration, adhesion, cell death and proliferation. TGF-beta
      has an important function in cancer where it can work as either a tumor
      suppressor or oncogene, depending on the cancer type and stage of tumor
      development. Since glioblastoma often have dysfunctional TGF-beta signaling we
      wanted to find out if there is any interaction between TLX and TGF-beta in
      glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical
      TGF-beta signaling response in glioblastoma cell lines. TLX physically interacts
      with and stabilizes Smurf1, which can ubiquitinate and target TGF-beta receptor
      II for degradation, whereas knockdown of TLX leads to stabilization of TGF-beta
      receptor II, increased nuclear translocation of Smad2/3 and enhanced expression
      of TGF-beta target genes. The interaction between TLX and TGF-beta may play an
      important role in the regulation of proliferation and tumor-initiating properties
      of glioblastoma cells.

PMID- 27048879
TI  - Immunization with a novel Clostridium perfringens epsilon toxin mutant
      rETX(Y196E)-C confers strong protection in mice.
AB  - Epsilon toxin (ETX) is produced by toxinotypes B and D of Clostridium
      perfringens. It can induce lethal enterotoxemia in domestic animals, mainly in
      sheep, goats and cattle, causing serious economic losses to global animal
      husbandry. In this study, a novel and stable epsilon toxin mutant rETX(Y196E)-C,
      obtained by substituting the 196th tyrosine (Y196) with glutamic acid (E) and
      introducing of 23 amino acids long C-terminal peptide, was determined as a
      promising recombinant vaccine candidate against enterotoxemia. After the third
      vaccination, the antibody titers against recombinant wild type (rETX) could reach
      1:10(5) in each immunized group, and the mice were completely protected from 100
      * LD50 (50% lethal dose) of rETX challenge. The mice in 15 MUg subcutaneously
      immunized group fully survived at the dose of 500 * LD50 of rETX challenge and
      80% of mice survived at 180 MUg (1000 * LD50) of rETX administration. In vitro,
      immune sera from 15 MUg subcutaneously immunized group could completely protect
      MDCK cells from 16 * CT50 (50% lethal dose of cells) of rETX challenge and
      protect against 10 * LD50 dose (1.8 MUg) of rETX challenge in mice. These data
      suggest that recombinant protein rETX(Y196E)-C is a potential vaccine candidate
      for future applied researches. 

PMID- 27048881
TI  - Ion-mediated single-molecular optical switching and sensing based on the
      fluorophore-tethered calix[4]pyrrole.
AB  - The design and synthesis of the first asymmetrically "two-walled"meso-substituted
      calix[4]pyrrole tethered by a fluorophore and its subsequent implication as an
      archetype sequential 'on-off-on-off' fluorescent single-molecular switch are
      reported. The current system permits us to extend the sensitivity up to sub
      nanomolar levels with the detection limit as low as 0.4 nM. 

PMID- 27048882
TI  - Designing graphene as a new frustrated Lewis pair catalyst for hydrogen
      activation by co-doping.
AB  - Boron and nitrogen co-doped bilayer graphene (BN-G) and graphene ribbon (BN-GR)
      as Frustrated Lewis Pair (FLP) catalysts are investigated for hydrogen molecule
      activation. The nitrogen and boron atoms are separated as they are in different
      layers of BN-G/GR. Calculations show that this novel FLP catalyst is capable of
      activating hydrogen molecules. From the Bader charge, Mayer bond order, and the
      geometrical structures, it can be seen that the hydrogen molecules undergo
      heterolytic scission and have a late product-like transition state. More
      interestingly, the active sites are identified as being the carbon atoms around
      dopants for BN-G. The BN-G/GR catalysts deliver performances comparable to that
      of the reported FLP catalyst when considering their barrier and reaction energy
      values. The current work demonstrates the great potential of doped carbon
      catalysts as FLP catalysts and paves the way to nanostructured carbon catalyst
      applications in reactions by directly utilizing hydrogen molecules. 

PMID- 27048880
TI  - Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine
      glioma.
AB  - Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours
      where needle biopsies help guide diagnosis and targeted therapies. To address
      spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical
      structures of whole autopsy brains from nine DIPG patients. Evolutionary
      reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations
      potentially arise first and are invariably associated with specific, high
      fidelity obligate partners throughout the tumour and its spread, from diagnosis
      to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M
      ubiquitously-associated mutations involve alterations in TP53 cell-cycle
      (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic
      alterations arise in sub-clones and often affect the PI3K pathway. Our findings
      are consistent with early tumour spread outside the brainstem including the
      cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG
      implies they will be captured by limited biopsies and emphasizes the need to
      develop therapies specifically targeting obligate oncohistone partnerships.

PMID- 27048883
TI  - Trophy Hunting Does and Will Support Biodiversity: A Reply to Ripple et al.

PMID- 27048884
TI  - Comparison of DNA Quantification Methods for Next Generation Sequencing.
AB  - Next Generation Sequencing (NGS) is a powerful tool that depends on loading a
      precise amount of DNA onto a flowcell. NGS strategies have expanded our ability
      to investigate genomic phenomena by referencing mutations in cancer and diseases
      through large-scale genotyping, developing methods to map rare chromatin
      interactions (4C; 5C and Hi-C) and identifying chromatin features associated with
      regulatory elements (ChIP-seq, Bis-Seq, ChiA-PET). While many methods are
      available for DNA library quantification, there is no unambiguous gold standard.
      Most techniques use PCR to amplify DNA libraries to obtain sufficient quantities
      for optical density measurement. However, increased PCR cycles can distort the
      library's heterogeneity and prevent the detection of rare variants. In this
      analysis, we compared new digital PCR technologies (droplet digital PCR; ddPCR,
      ddPCR-Tail) with standard methods for the titration of NGS libraries. DdPCR-Tail
      is comparable to qPCR and fluorometry (QuBit) and allows sensitive quantification
      by analysis of barcode repartition after sequencing of multiplexed samples. This
      study provides a direct comparison between quantification methods throughout a
      complete sequencing experiment and provides the impetus to use ddPCR-based
      quantification for improvement of NGS quality. 

PMID- 27048885
TI  - Andexanet: Effectively Reversing Anticoagulation.
AB  - Despite direct oral anticoagulants becoming a mainstay of anticoagulant therapy,
      the effective, timely, and safe reversal of their anticoagulant effect remains
      challenging. Emerging evidence attests that andexanet, a recombinant and inactive
      variant of native factor X (FXa), competitively inhibits and counteracts the
      anticoagulant effect of many inhibitors of native activated FXa.

PMID- 27048886
TI  - Catalytic N-radical cascade reaction of hydrazones by oxidative deprotonation
      electron transfer and TEMPO mediation.
AB  - Compared with the popularity of various C-centred radicals, the N-centred
      radicals remain largely unexplored in catalytic radical cascade reactions because
      of a lack of convenient methods for their generation. Known methods for their
      generation typically require the use of N-functionalized precursors or various
      toxic, potentially explosive or unstable radical initiators. Recently, visible
      light photocatalysis has emerged as an attractive tool for the catalytic
      formation of N-centred radicals, but the pre-incorporation of a photolabile
      groups at the nitrogen atom largely limited the reaction scope. Here, we present
      a visible-light photocatalytic oxidative deprotonation electron transfer/2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO)-mediation strategy for catalytic N-radical
      cascade reaction of unsaturated hydrazones. This mild protocol provides a broadly
      applicable synthesis of 1,6-dihydropyradazines with complete regioselectivity and
      good yields. The 1,6-dihydropyradazines can be easily transformed into diazinium
      salts that showed promising in vitro antifungal activities against fungal
      pathogens. DFT calculations are conducted to explain the mechanism. 

PMID- 27048887
TI  - High Color-Purity Green, Orange, and Red Light-Emitting Diodes Based on
      Chemically Functionalized Graphene Quantum Dots.
AB  - Chemically derived graphene quantum dots (GQDs) to date have showed very broad
      emission linewidth due to many kinds of chemical bondings with different energy
      levels, which significantly degrades the color purity and color tunability. Here,
      we show that use of aniline derivatives to chemically functionalize GQDs
      generates new extrinsic energy levels that lead to photoluminescence of very
      narrow linewidths. We use transient absorption and time-resolved
      photoluminescence spectroscopies to study the electronic structures and related
      electronic transitions of our GQDs, which reveals that their underlying carrier
      dynamics is strongly related to the chemical properties of aniline derivatives.
      Using these functionalized GQDs as lumophores, we fabricate light-emitting didoes
      (LEDs) that exhibit green, orange, and red electroluminescence that has high
      color purity. The maximum current efficiency of 3.47 cd A(-1) and external
      quantum efficiency of 1.28% are recorded with our LEDs; these are the highest
      values ever reported for LEDs based on carbon-nanoparticle phosphors. This
      functionalization of GQDs with aniline derivatives represents a new method to
      fabricate LEDs that produce natural color.

PMID- 27048888
TI  - Correction: Weak backbone CHO[double bond, length as m-dash]C and side chain
      tButBu London interactions help promote helix folding of achiral NtBu peptoids.
AB  - Correction for 'Weak backbone CHO[double bond, length as m-dash]C and side chain
      tButBu London interactions help promote helix folding of achiral NtBu peptoids'
      by G. Angelici et al., Chem. Commun., 2016, 52, 4573-4576.

PMID- 27048889
TI  - Electrospun nanofibers for cancer diagnosis and therapy.
AB  - The advent of nanotechnology has provided unprecedented opportunities for
      nanomedicine. Electrospun nanofibers have some astounding features such as high
      loading capacity, extremely large surface area and porosity, high encapsulation
      efficiency, ease of modification, combination of diverse therapies, low cost and
      great benefits. These remarkable structure-dependent properties have far reaching
      application potential in cancer diagnosis and therapy such as ultra-sensitive
      sensing systems for point-of-care cancer detection, targeted cancer cell capture,
      and functional and smart anticancer drug delivery systems. This review summarizes
      the principal mechanism of electrospun nanofibers and a variety of modified
      electrospun nanofibers, illustrates their application in biosensors for cancer
      detection, and enumerates their application in implantable drug delivery for
      cancer therapy. 

PMID- 27048890
TI  - Multifunctional solid-state electrochemiluminescence sensing platform based on
      poly(ethylenimine) capped N-doped carbon dots as novel co-reactant.
AB  - A multifunctional solid-state electrochemiluminescence (ECL) sensing platform
      based on poly(ethylenimine) (PEI) capped N-doped carbon dots (NCDs@PEI) as novel
      co-reactant of Ru(bpy)32+ nanosheets (RuNSs) was designed for the first time. In
      this route, RuNSs with large surface-to-volume ratio was used as luminophor, and
      NCDs@PEI, which was newly synthesized and modified in one step via a facile
      microwave-assisted method, was served as co-reactant. The as-prepared NCDs@PEI
      exhibited better catalytic effect to RuNSs than naked NCDs, due to the double
      enhancement contribution of NCDs and PEI to RuNSs. Simultaneously, reduced
      graphene oxide (rGO) was further introduced to facilitate the electron transfer
      and amplify the ECL signal. The developed ECL sensor (NCDs@PEI-rGO/RuNSs/GCE)
      exhibited desired ECL emission, with about 69-fold enhancement of the ECL
      intensity in comparison with RuNSs/GCE. When used as ECL probe for dopamine
      detection, the prepared sensor showed high sensitivity in a wide linear range of
      0.01-50MUM with the detection limit of 10nM. Moreover, the sensing platform also
      suggested multifunctional application for detecting other compounds including
      bisphenol A, catechol and hydroquinone.

PMID- 27048891
TI  - Preface.

PMID- 27048892
TI  - Dysbiosis in gastrointestinal disorders.
AB  - The recent development of advanced sequencing techniques has revealed the
      complexity and diverse functions of the gut microbiota. Furthermore, alterations
      in the composition or balance of the intestinal microbiota, or dysbiosis, are
      associated with many gastrointestinal diseases. The looming question is whether
      dysbiosis is a cause or effect of these diseases. In this review, we will
      evaluate the contribution of intestinal microbiota in obesity, fatty liver,
      inflammatory bowel disease, and irritable bowel syndrome. Promising results from
      microbiota or metabolite transfer experiments in animals suggest the microbiota
      may be sufficient to reproduce disease features in the appropriate host in
      certain disorders. Less compelling causal associations may reflect complex, multi
      factorial disease pathogenesis, in which dysbiosis is a necessary condition.
      Understanding the contributions of the microbiota in GI diseases should offer
      novel insight into disease pathophysiology and deliver new treatment strategies
      such as therapeutic manipulation of the microbiota. 

PMID- 27048893
TI  - Probiotics: definition, scope and mechanisms of action.
AB  - For a subject area of science, medicine and commerce to be so recently defined
      and investigated, few can compare to probiotics for the controversy they have
      incited. Barely a paper is published without the use of a different definition,
      or challenging the most used one, or proposing a different nuance of it. The
      situation has become even more surreal with the European Food and Safety
      Authority banning the word probiotic for use on labels. The reiteration of the
      FAO/WHO definition by the world's leading group of probiotic experts, should
      provide relative consistency in the near future, but what are the causes of these
      aberrations? This review will discuss the rationale for the definition, and the
      scope of the subject area and why alternatives emerge. While mechanisms of action
      are not widely proven, in vitro and some in vivo experiments support several.
      Ultimately, the goal of any field or product is to be understood by lay people
      and experts alike. Probiotics have come a long way in 100 years since Metchnikoff
      and 10 years since their globalization, but their evolution is far from over.

PMID- 27048894
TI  - Prebiotics: Definition and protective mechanisms.
AB  - The increase in chronic metabolic and immunologic disorders in the modern society
      is linked to major changes in the dietary patterns. These chronic conditions are
      associated with intestinal microbiota dysbiosis where important groups of
      carbohydrate fermenting, short-chain fatty acids-producing bacteria are reduced.
      Dietary prebiotics are defined as a selectively fermented ingredients that result
      in specific changes in the composition and/or activity of the gastrointestinal
      microbiota, thus conferring benefit(s) upon host health. Application of
      prebiotics may then restore the gut microbiota diversity and activity. Unlike the
      previously accepted prebiotics definition, where a limited number of bacterial
      species are involved in the prebiotic activity, new data from community-wide
      microbiome analysis demonstrated a broader affect of the prebiotics on the
      intestinal microbiota. These new findings require a revision of the current
      definition. In addition, prebiotics may exert immunomodulatory effects through
      microbiota-independent mechanisms that will require future investigations
      involving germ-free animal disease models. 

PMID- 27048895
TI  - Use of probiotics and prebiotics in infant feeding.
AB  - Gut colonization by beneficial bacteria in early life is necessary for
      establishing the gut mucosal barrier, maturation of the immune system and
      preventing infections with enteric pathogens. Mode of delivery, prematurity,
      breastfeeding, and use of antibiotics are some of many factors that have been
      described to influence early life colonization. Dysbiosis, the absence of normal
      colonization, is associated with many disease conditions. Pre- and probiotics are
      commonly used as supplementation in infant formula, such as prebiotic
      oligosaccharides for stimulation of Bifidobacterium growth aiming to mimic the
      high levels of these commensal bacteria in the gut of breastfed infants. Studies
      suggest that probiotic supplementation may be beneficial in prevention and
      management of disease (e.g., reducing the risk of necrotizing enterocolitis in
      preterm infants and treatment of acute gastroenteritis in children). Although
      these studies show promising beneficial effects, the long-term risks or health
      benefits of pre- and probiotic supplementation are not clear. 

PMID- 27048896
TI  - Probiotics and prebiotics in infectious gastroenteritis.
AB  - Acute gastroenteritis (AGE) is worldwide a common problem in infants and
      children. While AGE is still an important cause of morbidity and mortality in
      developing countries, it is mainly a problem with high socioeconomic impact in
      the rest of the world. Oral rehydration solutions (ORS) and rapid refeeding
      remain the cornerstone of the management. However, ORS does not decrease the
      duration of diarrhea. There is evidence that selected strains of probiotics
      decrease the duration of AGE with 24 h, both in ambulatory care and in
      hospitalized children, resulting also in a decrease of the duration of
      hospitalization. Synbiotics are equally effective as probiotics alone, but
      prebiotics are not effective. Both pro- and prebiotics have limited to no
      efficacy in the prevention of AGE. The administration of pre- and probiotics is
      considered to be safe, even in newborns. Only these pre-, pro and synbiotics that
      have been clinically tested can be recommended.

PMID- 27048897
TI  - Probiotics and prebiotics in ulcerative colitis.
AB  - The intestinal microbiota is one of the key players in the etiology of ulcerative
      colitis. Manipulation of this microflora with probiotics and prebiotics is an
      attractive strategy in the management of ulcerative colitis. Several intervention
      studies for both the induction and maintenance of remission in ulcerative colitis
      patients have been performed. Most of these studies evaluated VSL#3 or E. Coli
      Nissle 1917 and in general there is evidence for efficacy of these agents for
      induction and maintenance of remission. However, studies are frequently
      underpowered, lack a control group, and are very heterogeneous investigating
      different probiotic strains in different study populations. The absence of well
      powered robust randomized placebo-controlled trials impedes the widespread use of
      probiotics and prebiotics in ulcerative colitis. However, given the promising
      results that are currently available, probiotics and prebiotics may find their
      way to the treatment algorithm for ulcerative colitis in the near future. 

PMID- 27048898
TI  - The current place of probiotics and prebiotics in the treatment of pouchitis.
AB  - Pouchitis is a common complication in patients undergoing restorative
      proctocolectomy for ulcerative colitis. Therapeutic attempts include
      manipulations of pouch flora composition. In this review, we bring together the
      evidence supporting the use of probiotics and prebiotics in pouchitis patients,
      to clarify the place of these treatments in current therapeutic regimens. 

PMID- 27048899
TI  - Probiotics and prebiotics in Crohn's disease therapies.
AB  - Therapeutic manipulation of gut microbiota has proven valuable in the management
      of ulcerative colitis and pouchitis. Despite some similarities among the various
      inflammatory bowel conditions, the probiotics investigated thus far seem to
      confer little benefit in Crohn's disease. In this review, we aim to bring
      together the evidence available on the clinical effect of probiotics and
      prebioltics in Crohn's disease patients, and to clarify the place of probiotic
      treatment in current Crohn's therapeutic regimens. 

PMID- 27048900
TI  - Probiotics in functional bowel disorders.
AB  - Functional bowel disorders (FBDs) are the most common gastrointestinal (GI)
      disorders seen by gastroenterologists and primary care physicians. The disorders
      affect patients functioning and quality of life (QOL) and are associated with
      significant healthcare burden. The current theory regarding the development of
      FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and
      sensation. Recent data suggest that alterations in the intestinal microbiota may
      have a role in the pathogenesis of FBDs; or at least have the potential to affect
      intestinal functions that are thought to be relevant to the development of
      functional GI symptoms. This has led to growing interest of healthcare providers
      and patients in targeting the intestinal microbiota for the treatment of FBDs. In
      this article we discuss the potential role probiotic interventions in the
      treatment of FBDs. We review the evidence from pre-clinical and clinical studies
      and discuss the current recommendations for the use of probiotics for FBDs in
      clinical practice. 

PMID- 27048901
TI  - Probiotics in Helicobacter pylori-induced peptic ulcer disease.
AB  - The ideal treatment regimen for the eradication Helicobacter pylori infection has
      yet to be identified. Probiotics, particularly Lactobacillus, Bifidobacterium and
      Saccharomyces, have been suggested as adjuncts to antibiotics for the treatment
      of H. pylori. There is in vitro evidence that probiotics dampen the Th1 response
      triggered by H. pylori, attenuate H. pylori associated hypochlorhydria and
      secrete bacteriocidal metabolites. Probiotics interact with the innate host
      immune system through adherence to the gastric epithelium and secretion of
      bacterial adhesins. In prospective human studies, probiotic monotherapy
      effectively decrease H. pylori density (expired (13)CO2) by 2.0%-64.0%. Probiotic
      monotherapy has also been shown to eradicate H. pylori in up to 32.5%, although
      subsequent recrudescence is likely. Eleven meta-analyses have evaluated the
      efficacy of probiotics as adjuvants to antibiotics for the eradication of H.
      pylori. The addition of a probiotic increased treatment efficacy, OR 1.12-2.07.
      This benefit is probably strain-specific and may only be significant with
      relatively ineffective antibiotic regimens. The pooled prevalence of adverse
      effects was 12.9%-31.5% among subjects receiving adjuvant probiotics, compared
      with 24.3%-45.9% among controls. Diarrhea in particular was significantly reduced
      in subjects receiving adjuvant probiotics, compared with controls (OR 0.16-0.47).
      A reduction in adverse events other than diarrhea is variable. Despite the
      apparent benefit on efficacy and side effects conferred by probiotics, the
      optimal probiotic species, dose and treatment duration has yet to be determined.
      Further studies are needed to identify the probiotic, antibiotic and patient
      factors which might predict benefit from probiotic supplementation.

PMID- 27048902
TI  - Use of probiotics in prevention and treatment of patients with Clostridium
      difficile infection.
AB  - Clostridium difficile is an anaerobic, gram positive, sporulating, toxin
      producing bacillus which causes a spectrum of clinical disease ranging from an
      asymptomatic carrier state to toxic megacolon and fulminant disease. Infection
      with C. difficile is an expensive and pervasive health care burden. The current
      theory regarding the development of C. difficile infection (CDI) suggests that
      disruption of the structure and/or function of an individual's normal intestinal
      microbiota enables colonization by C. difficile, and in the absence of an
      effective immune response, the bacteria causes illness. In this article we
      discuss the role of the colonic microbiota in the development of CDI and the
      potential role of probiotics in preventing and treating CDI. We review the
      evidence from in vitro laboratory and pre-clinical studies, as well as evidence
      from clinical studies and discuss the current recommendations for the use of
      probiotics for CDI in clinical practice.

PMID- 27048903
TI  - Probiotics, prebiotics and colorectal cancer prevention.
AB  - Colorectal cancer (CRC), the third major cause of mortality among various cancer
      types in United States, has been increasing in developing countries due to
      varying diet and dietary habits and occupational hazards. Recent evidences showed
      that composition of gut microbiota could be associated with the development of
      CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and
      prebiotics, either alone or in combination could positively influence the cross
      talk between immune system and microbiota, would be beneficial in preventing
      inflammation and CRC. In this review, role of probiotics and prebiotics in the
      prevention of CRC has been discussed. Various epidemiological and experimental
      studies, specifically gut microbiome research has effectively improved the
      understanding about the role of probiotics and microbial treatment as
      anticarcinogenic agents. A few human studies support the beneficial effect of
      probiotics and prebiotics; hence, comprehensive understanding is urgent to
      realize the clinical applications of probiotics and prebiotics in CRC prevention.

PMID- 27048904
TI  - Intestinal microbiota in liver disease.
AB  - The intestinal microbiota have emerged as a topic of intense interest in
      gastroenterology and hepatology. The liver is on the front line as the first
      filter of nutrients, toxins and bacterial metabolites from the intestines and we
      are becoming increasingly aware of interactions among the gut, liver and immune
      system as important mediators of liver health and disease. Manipulating the
      microbiota with therapeutic intent is a rapidly expanding field. In this review,
      we will describe what is known about the contribution of intestinal microbiota to
      liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease
      including alcoholic and non-alcoholic fatty liver disease, cirrhosis and
      hepatocellular carcinoma; and the therapeutic manifestations of altering
      intestinal microbiota via antibiotics, prebiotics, probiotics and fecal
      microbiota transplantation. 

PMID- 27048906
TI  - In reply to ruling out white coat hypertension with NT-proBNP.

PMID- 27048905
TI  - SHEsisPlus, a toolset for genetic studies on polyploid species.
AB  - Currently, algorithms and softwares for genetic analysis of diploid organisms
      with bi-allelic markers are well-established, while those for polyploids are
      limited. Here, we present SHEsisPlus, the online algorithm toolset for both
      dichotomous and quantitative trait genetic analysis on polyploid species
      (compatible with haploids and diploids, too). SHEsisPlus is also optimized for
      handling multiple-allele datasets. It's free, open source and also designed to
      perform a range of analyses, including haplotype inference, linkage
      disequilibrium analysis, epistasis detection, Hardy-Weinberg equilibrium and
      single locus association tests. Meanwhile, we developed an accurate and efficient
      haplotype inference algorithm for polyploids and proposed an entropy-based
      algorithm to detect epistasis in the context of quantitative traits. A study of
      both simulated and real datasets showed that our haplotype inference algorithm
      was much faster and more accurate than existing ones. Our epistasis detection
      algorithm was the first try to apply information theory to characterizing the
      gene interactions in quantitative trait datasets. Results showed that its
      statistical power was significantly higher than conventional approaches.
      SHEsisPlus is freely available on the web at http://shesisplus.bio-x.cn/. Source
      code is freely available for download at
      https://github.com/celaoforever/SHEsisPlus. 

PMID- 27048907
TI  - Ruptured giant hepatic artery aneurysm.

PMID- 27048908
TI  - Torsion of Riedel's hepatic lobe simulating acute appendicitis.

PMID- 27048909
TI  - Autoimmune pancreatitis or pancreatic cancer?

PMID- 27048910
TI  - Groove pancreatitis vs. pancreatic adenocarcinoma: A review of 8 cases.
AB  - INTRODUCTION: Groove pancreatitis (PS) is an uncommon clinical situation and
      radiologically it can mimic carcinoma of the periampullary area. The aim of this
      paper is to study a series of 8 patients who underwent surgery with preoperative
      diagnosis of pancreatic head mass and subsequent pathological diagnosis of PS.
      METHODS: In our series, 6 were men and 2 women, with an average age of 51,9
      years. Before surgery, all patients had epigastric abdominal pain requiring
      analgesia at high doses. The preoperative analytical CEA and Ca 19.9 were normal
      in all patients. Imaging studies showed intrapancreatic solid lesions in 6 of the
      8 patients, and in the remaining 2 one papillary mass of 5 and 6cm, respectively,
      that caused stenosis in the duodenal luz. EUS neoplastic cells were negative in
      all patients. RESULTS: The immediate postoperative evolution was satisfactory,
      there are no complications. In our series, no patients have died. The long-term
      follow-up, in 7 of the 8 patients, has been excellent with disappearance of
      abdominal pain and improvement of nutritional status. The remaining patient had
      frequent recurrent episodes of acute pancreatitis, and at 60 months, presented a
      pseudocyst that has required a Roux-en-Y cystojejunostomy. CONCLUSIONS: PS must
      be included in the differential diagnosis of pancreatic lesions, which may
      include carcinoma of the periampullary area and other causes of chronic
      pancreatitis.

PMID- 27048911
TI  - Long-term safety and effectiveness of lurasidone in schizophrenia: a 22-month,
      open-label extension study.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of lurasidone in the long
      term treatment of patients with schizophrenia. METHODS: Patients who completed a
      6-week, double-blind (DB), placebo-controlled trial continued in a 22-month, open
      label (OL) study during which they received once-daily, flexible-doses of
      lurasidone, 40-120 mg. Change in the Positive and Negative Syndrome Scale (PANSS)
      was analyzed using both observed case (OC) and last observation carried forward
      (LOCF) analyses. RESULTS: Of the 251 patients who entered the OL extension, 51.4%
      completed 6 months, 36.7% completed 12 months, and 26.7% completed 22 months of
      OL treatment. Treatment with lurasidone was associated with a mean change from DB
      baseline, in weight of +0.4 kg at Month 12 (n=99), and +0.8 kg at Month 24 (n=67;
      OC analyses). Median change from DB baseline to Month 12 and Month 24,
      respectively, was -1.0 and -9.0 mg/dL for total cholesterol; 0.0 and -1.0 mg/dL
      for LDL; +1.0 and -11.0 mg/dL for triglycerides; and 0.0 and +0.1/% for HbA1c (OC
      analyses). The mean PANSS total score was 96.5 at DB baseline and 69.5 at OL
      baseline. The mean change from DB baseline in the PANSS total score at Month 24
      was -43.6 (OC) and -28.4 (LOCF). Thirty-seven patients (14.7%) discontinued due
      to an adverse event (AE) during OL treatment. Three AEs occurred in >=10% of
      patients: schizophrenia (12.4%), akathisia (10.8%), and somnolence (10.8%); and
      19.2% reported at least one movement disorder-related AE. Discontinuations due to
      AEs occurred in 14.8% of patients. CONCLUSIONS: In this 22-month, open-label
      extension study, treatment with lurasidone was associated with minimal effects on
      weight, glucose, lipids, and prolactin. Patients demonstrated sustained
      improvement in the PANSS total score for up to 24 months of lurasidone treatment.

PMID- 27048912
TI  - Short- and long-term outcomes of the absence of protein during bovine blastocyst
      formation in vitro.
AB  - In cattle, individual in vitro embryo culture after Day 6 benefits development,
      allowing non-invasive analysis of culture medium. However, undefined supplements
      in culture reduce analytical reliability. In this study we assayed the short- and
      long-term performance of embryos after bovine serum albumin removal over a 24-h
      period in individual culture. The absence of protein decreased embryo development
      and cell counts in the inner cell mass without affecting blastocyst sex ratio.
      However, the absence of protein produced embryos with an improved tendency to
      survive vitrification after 24h in culture (P=0.07). After transfer to
      recipients, birth rates of embryos that had been cultured with protein tended to
      decrease (P<0.06) mostly as a result of a higher number of miscarriages
      (P<0.013), reflecting lower viability. Birthweight, gestation length, height and
      thorax circumference did not differ between embryos cultured with or without
      protein. In fresh blastocysts cultured without protein, gene expression analysis
      showed higher abundance (P<0.05) of insulin-like growth factor 2 receptor (IGF2R;
      imprinting) and activating transcription factor 4 (ATF4) and DNA-damage-inducible
      transcript 3 (DDIT3; endoplasmic reticulum stress) transcripts, with DNA
      methyltransferase 3A (DNMT3A; imprinting) tending to increase (P=0.062). However,
      in hatched blastocysts that survived cryopreservation, glucose-6-phosphate
      dehydrogenase (G6PD) was overexpressed in embryos cultured without protein
      (P<0.01). The absence of protein results in fewer blastocysts but improved long
      term viability after cryopreservation.

PMID- 27048913
TI  - Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL.
AB  - Senescent cells, formed in response to physiological and oncogenic stresses,
      facilitate protection from tumourigenesis and aid in tissue repair. However,
      accumulation of such cells in tissues contributes to age-related pathologies.
      Resistance of senescent cells to apoptotic stimuli may contribute to their
      accumulation, yet the molecular mechanisms allowing their prolonged viability are
      poorly characterized. Here we show that senescent cells upregulate the anti
      apoptotic proteins BCL-W and BCL-XL. Joint inhibition of BCL-W and BCL-XL by
      siRNAs or the small-molecule ABT-737 specifically induces apoptosis in senescent
      cells. Notably, treatment of mice with ABT-737 efficiently eliminates senescent
      cells induced by DNA damage in the lungs as well as senescent cells formed in the
      epidermis by activation of p53 through transgenic p14(ARF). Elimination of
      senescent cells from the epidermis leads to an increase in hair-follicle stem
      cell proliferation. The finding that senescent cells can be eliminated
      pharmacologically paves the way to new strategies for the treatment of age
      related pathologies. 

PMID- 27048914
TI  - Integrated Metabolomics Study of the Milk of Heat-stressed Lactating Dairy Cows.
AB  - Heat stress (HS) damages the global dairy industry by reducing milk yields and
      quality, harming health, and damaging the reproduction of dairy cows, causing
      huge economic losses each year. However, an understanding of the physiological
      mechanism of HS lactating dairy cows remains elusive. Here, a metabolomics study
      using LC-MS and (1)H NMR spectroscopy was performed to analyze the metabolomic
      differences in the milk between HS-free and HS dairy cows, and discover
      diagnostic biomarkers and changes in the metabolic pathway. A total of 53
      discriminating metabolites were significantly up- or down-regulated in the HS
      group compared with the HS-free group (P < 0.05). These biomarkers were involved
      in pathways of carbohydrate, amino acid, lipid, and gut microbiome-derived
      metabolism. Comparing these potential biomarkers with previously identified HS
      candidate biomarkers in plasma, significant correlations between the levels of
      lactate, pyruvate, creatine, acetone, beta-hydroxybutyrate, trimethylamine, oleic
      acid, linoleic acid, lysophosphatidylcholine 16:0, and phosphatidylcholine 42:2
      in milk and plasma were found, indicating that the blood-milk barrier became
      leaky and the levels of these 10 biomarkers in milk can reflect HS-induced
      metabolomic alterations in blood. These novel findings can support more in-depth
      research to elucidate the milk-based changes in metabolic pathways in HS
      lactating dairy cows. 

PMID- 27048915
TI  - Facilitated diffusion in the presence of obstacles on the DNA.
AB  - Biological functions of DNA depend on the sequence-specific binding of DNA
      binding proteins to their corresponding binding sites. Binding of these proteins
      to their binding sites occurs through a facilitated diffusion process that
      combines three-dimensional diffusion in the cytoplasm with one-dimensional
      diffusion (sliding) along the DNA. In this work, we use a lattice model of
      facilitated diffusion to study how the dynamics of binding of a protein to a
      specific site (e.g., binding of an RNA polymerase to a promoter or of a
      transcription factor to its operator site) is affected by the presence of other
      proteins bound to the DNA, which act as 'obstacles' in the sliding process.
      Different types of these obstacles with different dynamics are implemented. While
      all types impair facilitated diffusion, the extent of the hindrance depends on
      the type of obstacle. As a consequence of hindrance by obstacles, more excursions
      into the cytoplasm are required for optimal target binding compared to the case
      without obstacles. 

PMID- 27048916
TI  - Dynamic control of cell adhesion on a stiffness-tunable substrate for analyzing
      the mechanobiology of collective cell migration.
AB  - A method was developed for photocontrolling cell adhesion on a gel substrate with
      defined mechanical properties. Precise patterning of geometrically controlled
      cell clusters and their migration induction became possible by spatiotemporally
      controlled photo-irradiation of the substrate. The clusters exhibited unique
      collective motion that depended on substrate stiffness and cluster geometry. 

PMID- 27048917
TI  - Difficult management of triple therapy for chronic hepatitis C in a patient on
      haemodialysis.

PMID- 27048918
TI  - Clinical practice guidelines for the management of constipation in adults. Part
      1: Definition, aetiology and clinical manifestations.
AB  - Clinical practice guidelines for the management of constipation in adults aim to
      generate recommendations on the optimal approach to chronic constipation in the
      primary care and specialized outpatient setting. Their main objective is to
      provide healthcare professionals who care for patients with chronic constipation
      with a tool that allows them to make the best decisions about the prevention,
      diagnosis and treatment of this condition. They are intended for family
      physicians, primary care and specialist nurses, gastroenterologists and other
      health professionals involved in the treatment of these patients, as well as
      patients themselves. The guidelines have been developed in response to the high
      prevalence of chronic constipation, its impact on patient quality of life and
      recent advances in pharmacological management. The Grading of Recommendations
      Assessment, Development and Evaluation Working Group (GRADE) system has been used
      to classify the scientific evidence and strengthen the recommendations.

PMID- 27048919
TI  - Altered intrinsic properties and bursting activities of neurons in layer IV of
      somatosensory cortex from Fmr-1 knockout mice.
AB  - Neuroadaptations and alterations in neuronal excitability are critical in brain
      maturation and many neurological diseases. Fragile X syndrome (FXS) is a
      pervasive neurodevelopmental disorder characterized by extensive synaptic and
      circuit dysfunction. It is still unclear about the alterations in intrinsic
      excitability of individual neurons and their link to hyperexcitable circuitry. In
      this study, whole cell patch-clamp recordings were employed to characterize the
      membrane and firing properties of layer IV cells in slices of the somatosensory
      cortex of Fmr-1 knockout (KO) mice. These cells generally exhibited a regular
      spiking (RS) pattern, while there were significant increases in the number of
      cells that adopted intrinsic bursting (IB) compared with age-matched wild type
      (WT) cells. The cells subgrouped according to their firing patterns and
      maturation differed significantly in membrane and discharge properties between KO
      and WT. The changes in the intrinsic properties were consistent with highly
      facilitated discharges in KO cells induced by current injection. Spontaneous
      activities of RS neurons driven by local network were also increased in the KO
      cells, especially in neonate groups. Under an epileptiform condition mimicked by
      omission of Mg(2+) in extracellular solution, these RS neurons from KO mice were
      more likely to switch to burst discharges. Analysis on bursts revealed that the
      KO cells tended to form burst discharges and even severe events manifested as
      seizure-like ictal discharges. These results suggest that alterations in
      intrinsic properties in individual neurons are involved in the abnormal
      excitability of cortical circuitry and possibly account for the pathogenesis of
      epilepsy in FXS.

PMID- 27048920
TI  - [Erratum to: Pathogenesis, clinical picture, and current therapy of rosacea].

PMID- 27048921
TI  - 3D-printing technologies for electrochemical applications.
AB  - Since its conception during the 80s, 3D-printing, also known as additive
      manufacturing, has been receiving unprecedented levels of attention and interest
      from industry and research laboratories. This is in addition to end users, who
      have benefited from the pervasiveness of desktop-size and relatively cheap
      printing machines available. 3D-printing enables almost infinite possibilities
      for rapid prototyping. Therefore, it has been considered for applications in
      numerous research fields, ranging from mechanical engineering, medicine, and
      materials science to chemistry. Electrochemistry is another branch of science
      that can certainly benefit from 3D-printing technologies, paving the way for the
      design and fabrication of cheaper, higher performing, and ubiquitously available
      electrochemical devices. Here, we aim to provide a general overview of the most
      commonly available 3D-printing methods along with a review of recent
      electrochemistry related studies adopting 3D-printing as a possible rapid
      prototyping fabrication tool.

PMID- 27048922
TI  - Apoptosis of Candida albicans during the Interaction with Murine Macrophages:
      Proteomics and Cell-Death Marker Monitoring.
AB  - Macrophages may induce fungal apoptosis to fight against C. albicans, as
      previously hypothesized by our group. To confirm this hypothesis, we analyzed
      proteins from C. albicans cells after 3 h of interaction with macrophages using
      two quantitative proteomic approaches. A total of 51 and 97 proteins were
      identified as differentially expressed by DIGE and iTRAQ, respectively. The
      proteins identified and quantified were different, with only seven in common, but
      classified in the same functional categories. The analyses of their functions
      indicated that an increase in the metabolism of amino acids and purine
      nucleotides were taking place, while the glycolysis and translation levels
      dropped after 3 h of interaction. Also, the response to oxidative stress and
      protein translation were reduced. In addition, seven substrates of metacaspase
      (Mca1) were identified (Cdc48, Fba1, Gpm1, Pmm1, Rct1, Ssb1, and Tal1) as
      decreased in abundance, plus 12 proteins previously described as related to
      apoptosis. Besides, the monitoring of apoptotic markers along 24 h of interaction
      (caspase-like activity, TUNEL assay, and the measurement of ROS and cell
      examination by transmission electron microscopy) revealed that apoptotic
      processes took place for 30% of the fungal cells, thus supporting the proteomic
      results and the hypothesis of macrophages killing C. albicans by apoptosis.

PMID- 27048923
TI  - Erythema Multiforme-Like Bullous Pemphigoid.

PMID- 27048924
TI  - Is it Solar Lentigo or Lentigo Maligna? (It Is Not a Nevus).

PMID- 27048925
TI  - Associations between the Brief Memory and Executive Test (BMET), Activities of
      Daily Living, and Quality of Life in Patients with Cerebral Small Vessel Disease.
AB  - OBJECTIVES: In addition to neuropsychological difficulties, patients with
      cerebral small vessel disease (SVD) can have reduced activities of daily living
      and a poorer quality of life compared to healthy adults. The Brief Memory and
      Executive Test (BMET), is a cognitive screening tool designed to be sensitive to
      the neuropsychological profile of patients with SVD. While the BMET is sensitive
      to the cognitive consequences of SVD, it is unclear how well scores on this
      measure relate to functional outcomes. The aims of this study are to investigate
      the relationship between scores on the BMET and functional outcomes (activities
      of daily living and quality of life) in SVD, and to compare this with other
      commonly used cognitive screening tools. METHODS: This study included 184
      participants with SVD (mean age=63.2; SD=9.9) and 299 healthy controls (mean
      age=62.4; SD=13.8) who were tested using the BMET, Montreal Cognitive Assessment
      (MoCA), Mini-Mental State Examination (MMSE), Stroke Specific - Quality of Life
      Scale (SS-QoL), Geriatric Depression Scale (GDS), and measures of both
      instrumental activities of daily living (IADL) and basic activities of daily
      living (BADL). RESULTS: After controlling for covariates the scores on the BMET,
      but not the MoCA or MMSE, were significantly related to poorer IADL and quality
      of life in the SVD group. In addition to the BMET scores, symptoms of depression
      were found to be significant associated with functional outcome. CONCLUSION:
      These results support the clinical utility of using of the BMET, in combination
      with a standardized depression questionnaire, during the early assessment of
      patients with SVD.

PMID- 27048926
TI  - A Circular Bioeconomy with Biobased Products from CO2 Sequestration.
AB  - The unprecedented climate change influenced by elevated concentrations of CO2 has
      compelled the research world to focus on CO2 sequestration. Although existing
      natural and anthropogenic CO2 sinks have proven valuable, their ability to
      further assimilate CO2 is now questioned. Thus, we highlight here the importance
      of biological sequestration methods as alternate and viable routes for mitigating
      climate change while simultaneously synthesizing value-added products that could
      sustainably fuel the circular bioeconomy. Four conceptual models for CO2
      biosequestration and the synthesis of biobased products, as well as an integrated
      CO2 biorefinery model, are proposed. Optimizing and implementing this biorefinery
      model might overcome the limitations of existing sequestration methods and could
      help realign the carbon balance.

PMID- 27048927
TI  - Biofluid infrared spectro-diagnostics: pre-analytical considerations for clinical
      applications.
AB  - Several proof-of-concept studies on the vibrational spectroscopy of biofluids
      have demonstrated that the methodology has promising potential as a clinical
      diagnostic tool. However, these studies also show that there is a lack of a
      standardised protocol in sample handling and preparation prior to spectroscopic
      analysis. One of the most important sources of analytical errors is the pre
      analytical phase. For the technique to be translated into clinics, it is clear
      that a very strict protocol needs to be established for such biological samples.
      This study focuses on some of the aspects of the pre-analytical phase in the
      development of the high-throughput Fourier Transform Infrared (FTIR) spectroscopy
      of some of the most common biofluids such as serum, plasma and bile. Pre
      analytical considerations that can impact either the samples (solvents, anti
      coagulants, freeze-thaw cycles...) and/or spectroscopic analysis (sample
      preparation such as drying, deposit methods, volumes, substrates, operators
      dependence...) and consequently the quality and the reproducibility of spectral
      data will be discussed in this report.

PMID- 27048928
TI  - Antiferromagnetic Spin Wave Field-Effect Transistor.
AB  - In a collinear antiferromagnet with easy-axis anisotropy, symmetry dictates that
      the spin wave modes must be doubly degenerate. Theses two modes, distinguished by
      their opposite polarization and available only in antiferromagnets, give rise to
      a novel degree of freedom to encode and process information. We show that the
      spin wave polarization can be manipulated by an electric field induced
      Dzyaloshinskii-Moriya interaction and magnetic anisotropy. We propose a prototype
      spin wave field-effect transistor which realizes a gate-tunable magnonic analog
      of the Faraday effect, and demonstrate its application in THz signal modulation.
      Our findings open up the exciting possibility of digital data processing
      utilizing antiferromagnetic spin waves and enable the direct projection of
      optical computing concepts onto the mesoscopic scale. 

PMID- 27048929
TI  - Expression levels and codon usage patterns in nuclear genes of the filarial
      nematode Wucheraria bancrofti and the blood fluke Schistosoma haematobium.
AB  - Synonymous codons are used with different frequencies, a phenomenon known as
      codon bias, which exists in many genomes and is mainly resolute by mutation and
      selection. To elucidate the genetic characteristics and evolutionary relationship
      of Wucheraria bancrofti and Schistosoma haematobium we examined the pattern of
      synonymous codon usage in nuclear genes of both the species. The mean overall GC
      contents of W. bancrofti and S. haematobium were 43.41 and 36.37%, respectively,
      which suggests that genes in both the species were AT rich. The value of the High
      Effective Number of Codons in both species suggests that codon usage bias was
      weak. Both species had a wide range of P3 distribution in the neutrality plot,
      with a significant correlation between P12 and P3. The codons were closer to the
      axes in correspondence analysis, suggesting that mutation pressure influenced the
      codon usage pattern in these species. We have identified the more frequently used
      codons in these species, most codons ending with an A or T. The nucleotides A/T
      and C/G were not proportionally used at the third position of codons, which
      reveals that natural selection might influence the codon usage patterns. The
      regression equation of P12 on P3 suggests that natural selection might have
      played a major role, while mutational pressure played a minor role in codon usage
      pattern in both species. These results form the basis of exploring the
      evolutionary mechanisms and the heterologous expression of medically important
      proteins of W. bancrofti and S. haematobium.

PMID- 27048930
TI  - Structural properties of Sb2S3 under pressure: evidence of an electronic
      topological transition.
AB  - High-pressure Raman spectroscopy and x-ray diffraction of Sb2S3 up to 53 GPa
      reveals two phase transitions at 5 GPa and 15 GPa. The first transition is
      evidenced by noticeable compressibility changes in distinct Raman-active modes,
      in the lattice parameter axial ratios, the unit cell volume, as well as in
      specific interatomic bond lengths and bond angles. By taking into account
      relevant results from the literature, we assign these effects to a second-order
      isostructural transition arising from an electronic topological transition in
      Sb2S3 near 5 GPa. Close comparison between Sb2S3 and Sb2Se3 up to 10 GPa reveals
      a slightly diverse structural behavior for these two compounds after the
      isostructural transition pressure. This structural diversity appears to account
      for the different pressure-induced electronic behavior of Sb2S3 and Sb2Se3 up to
      10 GPa, i.e. the absence of an insulator-metal transition in Sb2S3 up to that
      pressure. Finally, the second high-pressure modification appearing above 15 GPa
      appears to trigger a structural disorder at ~20 GPa; full decompression from 53
      GPa leads to the recovery of an amorphous state. 

PMID- 27048931
TI  - The origin of the supernumerary subunits and assembly factors of complex I: A
      treasure trove of pathway evolution.
AB  - We review and document the evolutionary origin of all complex I assembly factors
      and nine supernumerary subunits from protein families. Based on experimental data
      and the conservation of critical residues we identify a spectrum of protein
      function conservation between the complex I representatives and their non-complex
      I homologs. This spectrum ranges from proteins that have retained their molecular
      function but in which the substrate specificity may have changed or have become
      more specific, like NDUFAF5, to proteins that have lost their original molecular
      function and critical catalytic residues like NDUFAF6. In between are proteins
      that have retained their molecular function, which however appears unrelated to
      complex I, like ACAD9, or proteins in which amino acids of the active site are
      conserved but for which no enzymatic activity has been reported, like NDUFA10. We
      interpret complex I evolution against the background of molecular evolution
      theory. Complex I supernumerary subunits and assembly factors appear to have been
      recruited from proteins that are mitochondrial and/or that are expressed when
      complex I is active. Within the evolution of complex I and its assembly there are
      many cases of neofunctionalization after gene duplication, like ACAD9 and
      TMEM126B, one case of subfunctionalization: ACPM1 and ACPM2 in Yarrowia
      lipolytica, and one case in which a complex I protein itself appears to have been
      the source of a new protein from another complex: NDUFS6 gave rise to cytochrome
      c oxidase subunit COX4/COX5b. Complex I and its assembly can therewith be
      regarded as a treasure trove for pathway evolution. This article is part of a
      Special Issue entitled Respiratory complex I, edited by Volker Zickermann and
      Ulrich Brandt. 

PMID- 27048932
TI  - Deficiency in the mouse mitochondrial adenine nucleotide translocator isoform 2
      gene is associated with cardiac noncompaction.
AB  - The mouse fetal and adult hearts express two adenine nucleotide translocator
      (ANT) isoform genes. The predominant isoform is the heart-muscle-brain ANT
      isoform gene 1 (Ant1) while the other is the systemic Ant2 gene. Genetic
      inactivation of the Ant1 gene does not impair fetal development but results in
      hypertrophic cardiomyopathy in postnatal mice. Using a knockin X-linked Ant2
      allele in which exons 3 and 4 are flanked by loxP sites combined in males with a
      protamine 1 promoter driven Cre recombinase we created females heterozygous for a
      null Ant2 allele. Crossing the heterozygous females with the Ant2(fl), PrmCre(+)
      males resulted in male and female ANT2-null embryos. These fetuses proved to be
      embryonic lethal by day E14.5 in association with cardiac developmental failure,
      immature cardiomyocytes having swollen mitochondria, cardiomyocyte
      hyperproliferation, and cardiac failure due to hypertrabeculation/noncompaction.
      ANTs have two main functions, mitochondrial-cytosol ATP/ADP exchange and
      modulation of the mitochondrial permeability transition pore (mtPTP). Previous
      studies imply that ANT2 biases the mtPTP toward closed while ANT1 biases the
      mtPTP toward open. It has been reported that immature cardiomyocytes have a
      constitutively opened mtPTP, the closure of which signals the maturation of
      cardiomyocytes. Therefore, we hypothesize that the developmental toxicity of the
      Ant2 null mutation may be the result of biasing the cardiomyocyte mtPTP to remain
      open thus impairing cardiomyocyte maturation and resulting in cardiomyocyte
      hyperproliferation and failure of trabecular maturation. This article is part of
      a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva
      del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. 

PMID- 27048933
TI  - Neurologic and cognitive outcomes after aortic arch operation with hypothermic
      circulatory arrest.
AB  - BACKGROUND: Neurologic injury is still a frequent cause of mortality, morbidity,
      and long-lasting disability in patients undergoing an aortic arch operation with
      hypothermic circulatory arrest. The aim of this analysis was to evaluate short-
      and long-term outcomes in neurologic and cognitive functions in this group of
      high-risk patients. METHODS: A total of 333 patients undergoing an aortic arch
      operation between February 2004 and June 2010 were retrospectively reviewed.
      Cerebral protection was obtained with deep hypothermic circulatory arrest in 220
      patients (66%) or with moderate hypothermic circulatory arrest in 113 cases
      (34%). Straight deep hypothermic circulatory arrest was adopted in 35 cases
      (11%), while the association with antegrade cerebral perfusion was adopted in 271
      cases (81%) and with retrograde cerebral perfusion in 27 cases (8%). Seventy
      eight patients were enrolled in a case control prospective study (mean follow-up
      time = 42 months) and underwent neuropsychologic evaluations; data were compared
      with those of a matched-control group of hypertensive patients without history of
      cardiac operations. RESULTS: Forty-one out of 333 patients experienced permanent
      neurologic dysfunction (12%) and 83 experienced temporary neurologic dysfunctions
      (25%). Acute aortic dissection and deep hypothermic circulatory arrest were
      significant predictors of mortality and permanent neurologic dysfunction. Acute
      aortic dissection and hypothermic circulatory arrest duration >30 minutes were
      significant predictors of temporary neurologic dysfunction, while antegrade
      cerebral perfusion was protective on mortality. Neuropsychologic evaluations
      showed no significant differences between the groups. The operative group showed
      worse verbal and working memory (P = .003), worse semantic fluency (P = .036),
      higher degree of alexithymia (P = .004), and a lower quality of life (P = .007).
      CONCLUSION: Although moderate hypothermic circulatory arrest with antegrade
      cerebral perfusion demonstrated a lower mortality compared with deep hypothermic
      arrest, neurocognitive testing demonstrated no difference between the groups.
      Additionally, patients undergoing an aortic arch operation demonstrated long-term
      cognitive deficits and psychological dysfunction when compared to a matched
      cohort of nonoperative patients.

PMID- 27048934
TI  - Synchronous resections of hepatic oligometastatic pancreatic cancer: Disputing a
      principle in a time of safe pancreatic operations in a retrospective multicenter
      analysis.
AB  - BACKGROUND: The prognosis of patients with liver metastasis is generally
      considered dismal, and combined resections of the primary tumor and
      metastasectomies are not recommended. In highly selected patients, however,
      resections are performed. The evidence for this indication is limited. The aim of
      the current study was to assess the operative and oncologic outcomes of patients
      with combined pancreatic and liver resections of synchronous liver metastases.
      METHODS: In a retrospective analysis of 6 European pancreas centers, we
      identified 69 patients with pancreatic ductal adenocarcinoma and synchronous
      liver metastasis who underwent simultaneous pancreas and liver metastasis
      resections. Patients receiving exploration without tumor resection served as the
      control group. RESULTS: Overall survival (OS) appeared to be prolonged in the
      group of resected patients (median 14 vs 8 months, P < .001). Subgroup analysis
      revealed that the survival benefit of the resected patients was driven by
      pancreatic ductal adenocarcinomas localized in the pancreatic head (median OS
      13.6 vs 7 months, P < .001). Body/tail pancreatic ductal adenocarcinomas showed
      no benefit of resection (median OS 14 vs 15 months, P = .312). In the
      multivariate analysis, tumor resection was the only independent prognosticator
      for OS (hazard ratio 2.044, 95% confidence interval 1.342-3.114). CONCLUSION: The
      data of this retrospective and selective patient cohort suggested a clear
      survival benefit for patients undergoing synchronous pancreas and liver
      resections for pancreatic ductal adenocarcinoma, but due to the limitations of
      this retrospective study and very strong potential for selection bias, a strong
      conclusion for resection cannot be drawn. Prospective trials must validate these
      data and investigate the use of combined operative and systemic treatments in
      case of resectable metastatic pancreatic cancer. Is it time for a multicenter,
      prospective trial?

PMID- 27048935
TI  - Bariatric surgery outcomes in ethnic minorities.
AB  - BACKGROUND: The primary aim of this study was to examine percent excess weight
      loss (%EWL) across and between racial groups at 6, 12, 24, and 36 months follow
      up in patients who received sleeve gastrectomy (SG) or a Roux-en-Y gastric bypass
      (RYGB) operation. We hypothesized that ethnic minorities (blacks and Hispanics)
      would have a lower %EWL than whites at 6, 12, 24, and 36 months for both SG and
      RYGB operations. The secondary aim was to examine %EWL within racial groups at 6,
      12, 24, and 36 months as a function of the type of bariatric operation. We
      hypothesized that whites, blacks, and Hispanics would have a greater %EWL with
      RYGB than with SG. METHODS: A total of 749 patients who underwent an SG or an
      RYGB operation from January 2008 to June 2014 were included. Data were collected
      from patients' electronic medical records. Self-reported data on race/ethnicity
      were also obtained from the electronic medical record and were classified into
      the following categories: white, Hispanic/Latino, African American or black, or
      other. RESULTS: Results revealed overall differences in %EWL between blacks and
      whites (P < .05) and no overall differences in %EWL between Hispanics and whites
      (P = .697). Follow-up analyses revealed that Hispanics differed from blacks in
      %EWL at 6, 12, 24, and 36 months (all P < .01) and that whites differed from
      blacks at 6 months (P < .05). There were no significant differences between
      whites and Hispanics during any follow-up period. Overall, the %EWL differed by
      operation type (P < .01), with RYGB associated with greater %EWL than SG. When
      stratified by race, the only difference was found in blacks, who had a greater
      %EWL after RYGB compared with SG (P < .01). CONCLUSION: Our primary hypothesis
      was partially supported, as blacks but not Hispanics had a lower %EWL compared to
      whites at 6 months. An interesting finding is that blacks had a lower %EWL than
      Hispanics at every time point. Moreover, our secondary hypothesis was partially
      supported. Results revealed that overall RYGB was related to greater %EWL
      compared with SG, and within racial groups, among blacks only, RYGB was
      associated with a greater %EWL compared with SG.

PMID- 27048936
TI  - [Profile and initial management of infection in elderly patients in an Emergency
      Department].
AB  - OBJECTIVE: To determine the clinical profile and the initial management of
      elderly patients with acute infections attending Spanish Emergency Departments
      (EDs), and to analyse whether there are any differences compared to younger
      adults. MATERIAL AND METHODS: A descriptive, cross-sectional, multicentre study
      using the data recorded in the INFURG-SEMES register. It included a total of
      79,654 of 15 years or over treated for an acute infection in 49 Spanish EDs
      between 10 October 2010 and 20 September 2011. Demographic variables, clinical
      profile, and care in the ED, were collected. The classifying variable was to be
      65 years or over. RESULTS: Of the total of 11,399 cases, 4,255 (37.3%) were 65
      years or over. Statistically significant differences were found on comparing the
      elderly with the younger adults as regards the presence of a high comorbidity
      (P<.001), of at least one risk factor for multidrug resistance (P<.001), or
      septic syndrome (P<.001), type of infection (P<.001), taking of the specimen for
      blood culture (P<.001), determination of antigens in urine (P<.001), the
      antibiotic prescribed in the ED (P<.001), and final destination (P<.001).
      CONCLUSIONS: There are significant age-dependent differences in the profile and
      management of patients with infections that attend Spanish EDs, which must be
      taken into account when developing strategies for improving quality, as well as
      for future lines of research.

PMID- 27048937
TI  - Thiol/disulphide homeostasis as a novel indicator of oxidative stress in sudden
      sensorineural hearing loss.
AB  - OBJECTIVES: To investigate a novel oxidative stress marker, thiol/disulphide
      literature homeostasis, in patients with idiopathic sudden sensorineural hearing
      loss, and to compare the results with healthy controls for the first time.
      METHODS: Thirty-two patients with idiopathic sudden sensorineural hearing loss
      and 30 healthy individuals were included in the study. Serum native thiol, total
      thiol and disulphide levels were measured, and disulphide/native thiol and
      disulphide/total thiol ratios were determined in all subjects. RESULTS: Serum
      native thiol and total thiol levels were significantly lower in patients with
      sudden sensorineural hearing loss compared with controls (p < 0.05). Of the 32
      patients, 25 had lower native thiol levels than controls (333.2 +/- 73.9 vs 381.8
      +/- 35.6 MUmol/l, p = 0.002) and 24 had lower total thiol levels (375.1 +/- 74.3
      vs 426.1 +/- 39.3 MUmol/l, p = 0.002). CONCLUSION: The changes in oxidative
      markers evident in a significant number of patients may be associated with
      oxidative stress, which may, in turn, have caused sudden sensorineural hearing
      loss in those patients.

PMID- 27048939
TI  - Prospects for point-of-care pathogen diagnostics using surface-enhanced Raman
      scattering (SERS).
AB  - Surface-enhanced Raman scattering (SERS) has enabled the detection of pathogens
      and disease markers at extremely low levels. This review examines the potential
      impact of SERS in addressing unmet needs in pathogen diagnostics both in a
      traditional clinical setting and in the point of care (POC) arena. It begins by
      describing the strengths and weaknesses of today's diagnostics technologies in
      order to set a contextual stage for an overview which highlights a few of the
      many recent developments using SERS in biodefense, human and animal health, and
      monitoring food and water safety. These sections are followed by discussions of
      the challenges for the translation of these developments to POC settings,
      including the performance attributes and metrics for quantification of analytical
      and clinical figures of merit (e.g., limit of detection and clinical accuracy),
      and the pathways for large-scale test validation and the build-out of
      instrumentation and tests kits for POC deployment.

PMID- 27048938
TI  - SCF(SAP) controls organ size by targeting PPD proteins for degradation in
      Arabidopsis thaliana.
AB  - Control of organ size by cell proliferation and growth is a fundamental process,
      but the mechanisms that determine the final size of organs are largely elusive in
      plants. We have previously revealed that the ubiquitin receptor DA1 regulates
      organ size by repressing cell proliferation in Arabidopsis. Here we report that a
      mutant allele of STERILE APETALA (SAP) suppresses the da1-1 mutant phenotype. We
      show that SAP is an F-box protein that forms part of a SKP1/Cullin/F-box E3
      ubiquitin ligase complex and controls organ size by promoting the proliferation
      of meristemoid cells. Genetic analyses suggest that SAP may act in the same
      pathway with PEAPOD1 and PEAPOD2, which are negative regulators of meristemoid
      proliferation, to control organ size, but does so independently of DA1. Further
      results reveal that SAP physically associates with PEAPOD1 and PEAPOD2, and
      targets them for degradation. These findings define a molecular mechanism by
      which SAP and PEAPOD control organ size. 

PMID- 27048940
TI  - Nucleophilic substitution by amide nitrogen in the aromatic rings of [zn - H]+
      ions; the structures of the [b2 - H - 17]+ and [c1 - 17]+ ions.
AB  - Peptide radical cations that contain an aromatic amino acid residue cleave to
      give [zn - H]+ ions with [b2 - H - 17]+ and [c1 - 17](+) ions, the dominant
      products in the dissociation of [zn - H]+, also present in lower abundance in the
      CID spectra. Isotopic labeling in the aromatic ring of [YpiGG](+) establishes
      that in the formation of [b2 - H - 17]+ ions a hydrogen from the delta-position
      of the Y residue is lost, indicating that nucleophilic substitution on the
      aromatic ring has occurred. A preliminary DFT investigation of nine plausible
      structures for the [c1 - 17](+) ion derived from [Y(pi)GG](+) shows that two
      structures resulting from attack on the aromatic ring by oxygen and nitrogen
      atoms from the peptide backbone have significantly better energies than other
      isomers. A detailed study of [Y(pi)GG](+) using two density functionals, B3LYP
      and M06-2X, with a 6-31++G(d,p) basis set gives a higher barrier for attack on
      the aromatic ring of the [zn - H]+ ion by nitrogen than by the carbonyl oxygen.
      However, subsequent rearrangements involving proton transfers are much higher in
      energy for the oxygen-substituted isomer leading to the conclusion that the [c1 -
      17](+) ions are the products of nucleophilic attack by nitrogen, protonated 2,7
      dihydroxyquinoline ions. The [b2 - H - 17]+ ions are formed by loss of glycine
      from the same intermediates involved in the formation of the [c1 - 17](+) ions.

PMID- 27048941
TI  - An indirect ELISA for detection of Theileria spp. antibodies using a recombinant
      protein (rTlSP) from Theileria luwenshuni.
AB  - Theileria is a tick-borne, intracellular protozoan parasite of worldwide economic
      and veterinary importance in small ruminants. Here, an enzyme-linked
      immunosorbent assay (ELISA) was developed based on Theileria luwenshuni
      recombinant surface protein (rTlSP) and was used in the standardization and
      validation of an ELISA for the detection of circulating antibodies against ovine
      and caprine theileriosis. A total of 233 sera samples were used for the
      calculation of the cut-off value which served as a threshold between the positive
      and the negative sera. When the positive threshold was chosen as 19% of the
      specific mean antibody rate, the specificity was 97.9%, and the sensitivity was
      97.1%. There was a cross-reaction with sera against Theileria uilenbergi and
      Theileria ovis, and no cross-reaction with sera against Babesia spp. in the ELISA
      and Western blotting. Two hundred forty samples collected from sheep in Gansu
      province were detected with blood smears and ELISA, respectively. The results
      showed that the positive rate of Theileria infection in Gansu province were
      63.75% with rTlSP-ELISA, and 46.67% with blood smears, respectively. Our test
      proved that the rTlSP ELISA is suitable to diagnose Theileria infection and could
      be used in serological surveys to map out the prevalence of ovine and caprine
      theileriosis. 

PMID- 27048942
TI  - Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active
      benzofuran-pyridine hybrids.
AB  - Reaction of 3-aryl-1-(benzofuran-2-yl)-2-propen-1-ones 3a-c with malononitrile in
      the presence of sufficient amount of sodium alkoxide in the corresponding alcohol
      proceeds in a regioselective manner to afford 2-alkoxy-4-aryl-6-(benzofuran-2-yl)
      3-pyridinecarbonitriles 4-37, which also obtained by treating
      ylidenemalononitriles 6a-q with 2-acetylbenzofuran 1 in the presence of
      sufficient amount of sodium alkoxide in the corresponding alcohol. The new
      chemical entities showed significant vasodilation properties using isolated
      thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride
      standard technique. Compounds 11, 16, 21, 24 and 30 exhibited remarkable activity
      compared with amiodarone hydrochloride the reference standard used in the present
      study. CODESSA-Pro software was employing to obtain a statistically significant
      QSAR model describing the bioactivity of the newly synthesized analogs (N=31,
      n=5, R(2)=0.846, R(2)cvOO=0.765, R(2)cvMO=0.778, F=27.540. s(2)=0.002).

PMID- 27048944
TI  - Rh(III)-catalyzed relay carbenoid functionalization of aromatic C-H bonds: access
      to pi-conjugated fused heteroarenes.
AB  - A novel Rh(III)-catalyzed relay cross-coupling/cyclization cascade between
      arylketoimines and diazoesters is described. This transformation provides a
      concise access to unique pi-conjugated 1-azaphenalenes (1-APLEs) via a double
      aryl Csp(2)-H bond carbenoid functionalization process. As illustrative examples,
      the 1-APLE-based pi-conjugated molecules which possess low-lying HOMO levels
      could be converted to promising organic optoelectronic materials.

PMID- 27048943
TI  - Synthesis and pharmacological evaluation of mono-arylimidamides as
      antileishmanial agents.
AB  - Arylimidamide (AIA) compounds containing two pyridylimidamide terminal groups
      (bis-AIAs) possess outstanding in vitro antileishmanial activity, and the
      frontrunner bis-AIA DB766 (2,5-bis[2-(2-isopropoxy)-4-(2
      pyridylimino)aminophenyl]furan) is active in visceral leishmaniasis models when
      given orally. Eighteen compounds containing a single pyridylimidamide terminal
      group (mono-AIAs) were synthesized and evaluated for their antileishmanial
      potential. Six of these compounds exhibited sub-micromolar potency against both
      intracellular Leishmania donovani and Leishmania amazonensis amastigotes, and
      three of these compounds also displayed selectivity indexes of 25 or greater for
      the parasites compared to a J774 macrophage cell line. When given orally at a
      dose of 100mg/kg/day for five days, compound 1b (N-(3-isopropoxy-4-(5-phenylfuran
      2-yl)phenyl)picolinimidamide methanesulfonate) reduced liver parasitemia by 46%
      in L. donovani-infected mice. Mono-AIAs are thus a new class of candidate
      molecules for antileishmanial drug development.

PMID- 27048945
TI  - Surgical management of rectal carcinoids: trends and outcomes from the
      Surveillance, Epidemiology, and End Results database (1988 to 2012).
AB  - BACKGROUND: Local excision of small (<10 mm) rectal carcinoids is a standard
      treatment. Actual patterns of care and outcomes are understudied because of the
      rarity of this tumor. METHODS: Surveillance, Epidemiology, and End Results
      database (1988 to 2012) was interrogated for rectal carcinoid patients. Chi
      square testing and Kaplan-Meier survival analysis were used to compare survival
      outcomes. RESULTS: Of all, 11,329 patients were identified-9,605 with only
      localized disease. The majority (77%) underwent local excision only. Full rectal
      resection was performed more frequently for tumors greater than 10 mm (11.7% to
      12.2%) than for tumors less than 10 mm (4.5% to 4.9%, P < .001), and for higher T
      stage (T1: 4.0%, T2: 11.4%, T3/4:30.4%, P < .001). Nonoperative management was
      more common after year 2000 (11.2% to 13.7%) than prior (7.4% to 8.5%, P < .001).
      Cancer-specific survival improved across time periods but did not differ between
      nonoperative, local excision, or surgical resection. CONCLUSIONS: Nonexcisional
      management of small, localized rectal carcinoids is becoming more common and may
      offer equivalent survival to excision or resection.

PMID- 27048946
TI  - Dual-energy X-ray absorptiometry body composition in patients with secondary
      osteoporosis.
AB  - Due to the tight relationship between bone and soft tissues, there has been an
      increased interest in body composition assessment in patients with secondary
      osteoporosis as well as other pathological conditions. Dual-energy X-ray
      absorptiometry (DXA) is primarily devoted to the evaluation of bone mineral
      status, but continuous scientific advances of body composition software made DXA
      a rapid and easily available technique to assess body composition in terms of fat
      mass and lean mass. As a result, the International Society for Clinical
      Densitometry (ISCD) recently developed Official Positions regarding the use of
      this technique for body composition analysis. According to ISCD paper,
      indications are mainly limited to three conditions: HIV patients treated with
      antiretroviral agents associated with a risk of lipoatrophy; obese patients
      undergoing treatment for high weight loss; patients with sarcopenia or muscle
      weakness. Nevertheless, there are several other interesting clinical applications
      that were not included in the ISCD position paper, such as body composition
      assessment in patients undergoing organ transplantation, pulmonary disease as
      well as all those chronic condition that may lead to malnutrition. In conclusion,
      DXA body composition offers new diagnostic and research possibilities for a
      variety of diseases; due to its high reproducibility, DXA has also the potential
      to monitor body composition changes with pharmacological, nutritional or physic
      therapeutic interventions. ISCD addressed and recommended a list of clinical
      condition, but the crescent availability of DXA scans and software improvements
      may open the use of DXA to other indication in the next future. This article
      provides an overview of DXA body composition indications in the management of
      secondary osteoporosis and other clinical indications in adults. 

PMID- 27048947
TI  - Dietary patterns extracted from the current Japanese diet and their associations
      with sodium and potassium intakes estimated by repeated 24 h urine collection.
AB  - OBJECTIVE: To identify dietary patterns in the current Japanese diet and evaluate
      the associations between these patterns and Na and K intakes. DESIGN: Dietary
      patterns were extracted by factor analysis from the intakes of food groups
      assessed with a validated self-administrated diet history questionnaire. Na and K
      intakes and urinary Na:K were assessed by repeated 24 h urine collection.
      SUBJECTS: Healthy Japanese adults aged 20-69 years (353 men and 349 women).
      SETTING: Twenty study areas in twenty-three prefectures in Japan. Result Four
      dietary patterns were identified in each sex. After adjustment for several
      confounding factors, the 'Fish and vegetable' pattern was associated with higher
      urinary Na excretion, but the association was not significant (P=0.37 in men and
      P=0.06 in women). This pattern was also associated with higher K excretion in
      both sexes. The 'Noodle' pattern tended to be associated with higher urinary Na
      excretion (P=0.17 in men and P=0.04 in women) and higher Na:K (P=0.02 in men).
      The 'Meat, vegetable and oil' (in men)/'Meat and oil' (in women) and 'Bread and
      confectioneries' patterns were not associated with urinary Na excretion (in men)
      or were negatively associated (in women). CONCLUSIONS: Contrary to the case in
      Western countries, the 'Fish and vegetable' and 'Noodle' patterns contributed to
      higher Na intake in Japan. Target foods for salt reduction should be set based on
      careful consideration of the relationships between dietary patterns and Na and K
      intakes in the target population.

PMID- 27048948
TI  - Food allergy prevalence and management at an overnight summer camp.
AB  - BACKGROUND: In recent years, increased awareness of food allergy management has
      focused on the school setting. A lack of awareness and relevant literature
      prompted evaluation of the camp experience. OBJECTIVE: To characterize the
      prevalence of food allergies among children attending an overnight summer camp
      and to evaluate the knowledge and comfort of camp personnel before and after a
      training session. METHODS: The database for the 2014 season at Flying Horse Farms
      was reviewed for information pertaining to food allergies and provision of
      epinephrine and treatment plans. Camp personnel completed surveys regarding food
      allergy knowledge and comfort. Surveys were redistributed 30 days after the
      training session. RESULTS: Among 445 campers, 15% reported at least one food
      allergy, with 8.5% reporting allergy to 1 of the top 8 food allergens. Only 32%
      of campers with food allergy supplied an epinephrine autoinjector, and 0%
      provided written treatment plans. Before training, 84% of personnel desired
      additional information about food allergies. Knowledge of food allergies among
      personnel was high at baseline but increased after training in regard to
      epinephrine use for anaphylaxis and postepinephrine management. Staffers who
      reported feeling very comfortable caring for campers with food allergy increased
      from 16% to 46% after the training session; comfort in treating a food allergy
      emergency increased from 2% to 29%. CONCLUSION: Management of food allergies at
      overnight summer camps warrants similar education and preparation strategies as
      those implemented in schools. Camp personnel should receive annual training
      regarding food allergies and anaphylaxis.

PMID- 27048949
TI  - Characteristics of laryngeal symptoms induced in patients with allergic rhinitis
      in an environmental challenge chamber.
AB  - BACKGROUND: People with allergic rhinitis often have laryngeal symptoms (LSs) in
      addition to nasal symptoms during the pollen-scattering season. OBJECTIVE: To
      clarify the characteristics of the LSs induced by pollen exposure using an
      environmental challenge chamber. METHODS: Cypress pollen exposure using an
      environmental challenge chamber for 25 participants with cypress pollen-induced
      allergic rhinitis was performed for 3 hours for 2 consecutive days in 3 study
      courses: namely, pollen exposure under normal nasal breathing and pollen or sham
      pollen exposure with nasal blockage, which eliminated any allergic reactions in
      the nasal mucosa. The nasal and LSs scores and the levels of serum inflammatory
      mediators, including eosinophil cationic protein (ECP), were monitored. Laryngeal
      examinations and physiologic lung tests were also conducted. RESULTS: Various LSs
      were reported, and these LSs were significantly elevated during pollen exposure
      and even under sham exposure with artificial nasal blockage. The pollen exposure
      with artificial nasal blockage exaggerated the LSs in 32% of the participants and
      also increased the serum ECP levels. The serum ECP levels did not change after
      sham exposure. The findings of both laryngeal examinations and lung tests failed
      to reveal any significant changes. CONCLUSION: Nasal obstruction could induce
      significant LSs even without pollen exposure. LSs were enhanced by pollen
      exposure and allergic reactions in the larynx could thus be involved in this
      enhancement. TRIAL REGISTRATION: clinicaltrials.gov Identifier: UMIN000015667.

PMID- 27048950
TI  - Xq22.1 contiguous gene deletion syndrome of X-linked agammaglobulinemia and Mohr
      Tranebjaerg syndrome.

PMID- 27048951
TI  - A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E
      Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice.
AB  - Acquired resistance to vemurafenib develops through reactivation of RAF/MEK/ERK
      signaling or bypass mechanisms. Recent combination therapies such as a MEK
      inhibitor combined with vemurafenib show improvement in major clinical end
      points, but the percentage of patients with adverse toxic events is higher than
      with vemurafenib monotherapy and most patients ultimately relapse. Therefore,
      there is an urgent need to develop new antimelanoma drugs and/or adjuvant agents
      for vemurafenib therapy. In this study, we created a novel semiorganically
      modified derivative, DETD-35, from deoxyelephantopin (DET), a plant sesquiterpene
      lactone demonstrated as an anti-inflammatory and anti-mammary tumor agent. Our
      results show that DETD-35 inhibited proliferation of a panel of melanoma cell
      lines, including acquired vemurafenib resistance A375 cells (A375-R) established
      in this study, with superior activities to DET and no cytotoxicity to normal
      melanocytes. DETD-35 suppressed tumor growth and reduced tumor mass as
      effectively as vemurafenib in A375 xenograft study. Furthermore, DETD-35 also
      reduced tumor growth in both acquired (A375-R) and intrinsic (A2058) vemurafenib
      resistance xenograft models, where vemurafenib showed no antitumor activity.
      Notably, the combination of DETD-35 and vemurafenib exhibited the most
      significant effects in both in vitro and in vivo xenograft studies due to
      synergism of the compound and the drug. Mechanistic studies suggested that DETD
      35 overcame acquired vemurafenib resistance at least in part through deregulating
      MEK-ERK, Akt, and STAT3 signaling pathways and promoting apoptosis of cancer
      cells. Overall, our results suggest that DETD-35 may be useful as a therapeutic
      or adjuvant agent against BRAF(V600E) mutant and acquired vemurafenib resistance
      melanoma. Mol Cancer Ther; 15(6); 1163-76. (c)2016 AACR.

PMID- 27048953
TI  - Substrate and Inhibitor Specificity of the Plasmodium berghei Equilibrative
      Nucleoside Transporter Type 1.
AB  - Malaria is a critical public health issue in the tropical world, causing
      extensive morbidity and mortality. Infection by unicellular, obligate
      intracellular Plasmodium parasites causes malaria. The emergence of resistance to
      current antimalarial drugs necessitates the development of novel therapeutics. A
      potential novel drug target is the purine import transporter. Because Plasmodium
      parasites are purine auxotrophic, they must import purines from their host to
      fulfill metabolic requirements. They import purines via equilibrative nucleoside
      transporter 1 (ENT1) homologs. Recently, we used a yeast-based high-throughput
      screen to identify inhibitors of the P. falciparum ENT1 (PfENT1) that kill P.
      falciparum parasites in culture. P. berghei infection of mice is an animal model
      for human malaria. Because P. berghei ENT1 (PbENT1) shares only 60% amino acid
      sequence identity with PfENT1, we sought to characterize PbENT1 and its
      sensitivity to our PfENT1 inhibitors. We expressed PbENT1 in purine auxotrophic
      yeast and used radiolabeled substrate uptake to characterize its function. We
      showed that PbENT1 transports both purines and pyrimidines. It preferred
      nucleosides compared with nucleobases. Inosine (IC50 = 3.7 uM) and guanosine
      (IC50 = 21.3 uM) had the highest affinities. Our recently discovered PfENT1
      inhibitors were equally effective against both PbENT1- and PfENT1-mediated purine
      uptake. The PfENT1 inhibitors are at least 10-fold more potent against PfENT1
      than human hENT1. They kill P. berghei parasites in 24-hour ex vivo culture.
      Thus, the P. berghei murine malaria model may be useful to evaluate the efficacy
      of PfENT1 inhibitors in vivo and their therapeutic potential for treatment of
      malaria.

PMID- 27048952
TI  - Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic
      Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
AB  - PI3K plays a key role in cellular metabolism and cancer. Using a mass
      spectrometry-based metabolomics platform, we discovered that plasma
      concentrations of 26 metabolites, including amino acids, acylcarnitines, and
      phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors
      compared with non-tumor-bearing controls and in addition were increased following
      dosing with class I PI3K inhibitor pictilisib (GDC-0941). These candidate
      metabolomics biomarkers were evaluated in a phase I dose-escalation clinical
      trial of pictilisib. Time- and dose-dependent effects were observed in patients
      for 22 plasma metabolites. The changes exceeded baseline variability, resolved
      after drug washout, and were recapitulated on continuous dosing. Our study
      provides a link between modulation of the PI3K pathway and changes in the plasma
      metabolome and demonstrates that plasma metabolomics is a feasible and promising
      strategy for biomarker evaluation. Also, our findings provide additional support
      for an association between insulin resistance, branched-chain amino acids, and
      related metabolites following PI3K inhibition. Mol Cancer Ther; 15(6); 1412-24.
      (c)2016 AACR.

PMID- 27048954
TI  - Memantine augmentation in clozapine-refractory schizophrenia: a randomized,
      double-blind, placebo-controlled crossover study.
AB  - BACKGROUND: Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA)
      receptor hypofunction may be a causal factor for memory and executive
      dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the
      prefrontal cortex may also explain negative and positive symptoms. Clozapine
      augmentation with memantine targets altered NMDA receptor-mediated
      neurotransmission in schizophrenia and showed substantial beneficial effects on
      several symptom domains in a small proof-of-concept study. We evaluate effects of
      memantine add-on treatment to clozapine for memory and executive function, and
      negative and positive symptoms in schizophrenia. METHOD: Clozapine-treated
      patients with refractory schizophrenia were randomly assigned to 12 weeks of
      double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26).
      Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were
      change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on
      memory and executive function using the Cambridge Neuropsychological Test
      Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and
      Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed
      using the Liverpool University Neuroleptic Side-Effect Rating Scale. RESULTS:
      When compared with placebo, memantine improved a composite memory score
      comprising verbal recognition memory and paired associates learning task scores
      on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size
      = 0.29). Side effects were mild and transient. CONCLUSIONS: In patients with
      clozapine-treated refractory schizophrenia, memantine addition significantly
      improved verbal and visual memory and negative symptoms without serious adverse
      effects. These results justify further investigations on long-term memantine
      augmentation to clozapine in treatment-resistant schizophrenia.

PMID- 27048956
TI  - Nitinol clip distal migration and resultant popliteo-tibial artery occlusion
      complicating access closure by the StarClose SE vascular closure system.
AB  - Lower extremity ischemia following deployment of a vascular closure device for
      access site closure after a transfemoral endovascular procedure rarely occurs. A
      68-year-old woman diagnosed with subarachnoid hemorrhage due to a ruptured
      anterior communicating aneurysm was treated by endovascular coil embolization.
      The StarClose SE device was deployed for right femoral arteriotomy closure. After
      2 days, critical ischemia occurred on her right lower leg due to total occlusion
      of the popliteo-tibial artery. Emergent surgical embolectomy was performed and
      the nitinol clip of the StarClose device was captured in the lumen of the
      tibioperoneal trunk. Although StarClose is an extravascular closure system,
      intravascular deployment, distal migration, and resultant critical limb ischemia
      can occur.

PMID- 27048955
TI  - Imaging of Angiotropism/Vascular Co-Option in a Murine Model of Brain Melanoma:
      Implications for Melanoma Progression along Extravascular Pathways.
AB  - Angiotropism/pericytic mimicry and vascular co-option involve tumor cell
      interactions with the abluminal vascular surface. These two phenomena may be
      closely related. However, investigations of the two processes have developed in
      an independent fashion and different explanations offered as to their biological
      nature. Angiotropism describes the propensity of tumor cells to spread distantly
      via continuous migration along abluminal vascular surfaces, or extravascular
      migratory metastasis (EVMM). Vascular co-option has been proposed as an
      alternative mechanism by which tumors cells may gain access to a blood supply. We
      have used a murine brain melanoma model to analyze the interactions of GFP human
      melanoma cells injected into the mouse brain with red fluorescent lectin-labeled
      microvascular channels. Results have shown a striking spread of melanoma cells
      along preexisting microvascular channels and features of both vascular co-option
      and angiotropism/pericytic mimicry. This study has also documented the
      perivascular expression of Serpin B2 by angiotropic melanoma cells in the murine
      brain and in human melanoma brain metastases. Our findings suggest that vascular
      co-option and angiotropism/pericytic mimicry are closely related if not identical
      processes. Further studies are needed in order to establish whether EVMM is an
      alternative form of cancer metastasis in addition to intravascular cancer
      dissemination. 

PMID- 27048958
TI  - Hemodynamic differences between unstable and stable unruptured aneurysms
      independent of size and location: a pilot study.
AB  - BACKGROUND: While clinical and angiographic risk factors for intracranial
      aneurysm instability are well established, it is reasonable to postulate that
      intra-aneurysmal hemodynamics also have a role in aneurysm instability.
      OBJECTIVE: To identify hemodynamic characteristics that differ between
      radiologically unstable and stable unruptured intracranial aneurysms. MATERIALS
      AND METHODS: 12 pairs of unruptured intracranial aneurysms with a 3D rotational
      angiographic set of images and followed up longitudinally without treatment were
      studied. Each pair consisted of one stable aneurysm (no change on serial imaging)
      and one unstable aneurysm (demonstrated growth of at least 1 mm diameter or
      ruptured during follow-up) of matching size (within 10%) and locations. Patient
      specific computational fluid dynamics models were created and run under pulsatile
      flow conditions. Relevant hemodynamic and geometric variables were calculated and
      compared between groups using the paired Wilcoxon test. RESULTS: The area of the
      aneurysm under low wall shear stress (low shear stress area (LSA)) was 2.26 times
      larger in unstable aneurysms than in stable aneurysms (p=0.0499). The mean
      aneurysm vorticity was smaller by a factor of 0.57 in unstable aneurysms compared
      with stable aneurysms (p=0.0499). No statistically significant differences in
      geometric variables or shape indices were found. CONCLUSIONS: This pilot study
      suggests there may be hemodynamic differences between unstable and stable
      unruptured cerebral aneurysms. In particular, the area under low wall shear
      stress was larger in unstable aneurysms. These findings should be considered
      tentative until confirmed by future larger studies.

PMID- 27048957
TI  - Streamlining door to recanalization processes in endovascular stroke therapy.
AB  - BACKGROUND: In acute stroke due to large vessel occlusion, faster reperfusion
      leads to better outcomes. We analyzed the effect of optimization steps aimed to
      reduce treatment delays at our center. METHODS: Consecutive patients with
      ischemic stroke treated with endovascular therapy were prospectively analyzed. We
      divided the patients into pre-optimization (20 April 2012 to 8 October 2013) and
      post-optimization (9 October 2013 to 29 July 2014) periods. The main
      interventions included: (1) continuous feedback; (2) standardized immediate
      emergency department attending to stroke attending communication with
      interventional team activation for all potential interventions; (3) pre
      notification by the emergency medical service; (4) minimizing additional
      diagnostic testing; (5) direct transport to the CT scanner; (6) transport
      directly from the CT scanner to the angiography suite. The main metric used to
      measure improvement was door to groin puncture time (D2P). RESULTS: We included a
      total of 286 patients (178 pre-optimization, 108 post-optimization). There were
      no significant differences between major baseline characteristics between the
      groups with the exception of higher median CT Alberta Stroke Program Early CT
      Score in the pre-optimization group (p=0.01). Median D2P improved from 105 min
      pre-optimization to 67 min post-optimization (p=0.0002). Rates of good clinical
      outcomes (modified Rankin Scale 0-2 at 3 months) were similar in both groups,
      with a trend toward a better outcome in the post-optimization group in a subgroup
      analysis of patients with anterior circulation occlusion who received intravenous
      tissue plasminogen activator. CONCLUSIONS: This pilot study demonstrates that D2P
      times can be significantly reduced with a standardized multidisciplinary
      approach. There was no significant difference in the rate of 3-month good
      outcome, which is most likely due to the small sample size and confounding
      baseline patient characteristics.

PMID- 27048959
TI  - Three-dimensional image fusion of CTA and angiography for real-time guidance
      during neurointerventional procedures.
AB  - AIM: To evaluate the accuracy of three-dimensional (3D) images from two
      modalities-CT angiography (CTA) and digital subtraction angiography (DSA).
      Additionally, to explore the value of using preprocedural CTA for real-time
      guidance during neurointerventional procedures. MATERIALS AND METHODS: 25
      patients with CTA-confirmed cerebral arterial lesions were enrolled. For 12 of
      these patients, 3D DSA images of the contrast medium-enhanced target vessel were
      acquired during the intervention and registered with the preprocedurally acquired
      CTA images for evaluation of the accuracy of image fusion, focusing on the target
      vessel and the lesion. For the other 13 patients, a low-dose non-contrast 3D
      angiographic scan was performed. The preprocedurally acquired CTA image was then
      registered with the coordinate of angiography and overlaid onto the live
      fluoroscopic image to provide interventional guidance. RESULTS: Based on visual
      inspection by two experienced physicians and quantitative evaluation, excellent
      accuracy in the 3D registration of the CTA and DSA was achieved for all 12
      patients examined. Additionally, CTA could be used successfully to guide the
      interventional procedures, including both diagnostic DSA and stent treatment. The
      radiation dose and contrast medium use were compared with those used by
      conventional interventional procedures and both were found to be significantly
      reduced. CONCLUSIONS: 3D CTA and angiographic image fusion was approved as highly
      accurate for neurovasculature. Additionally, using the fusion technique to guide
      interventional procedures enhanced the workflow, and required much less radiation
      exposure and contrast medium use, thus helping to reduce potential risks and
      increase treatment safety.

PMID- 27048960
TI  - Direct to embolectomy without IV tPA: the stage is set for a randomized
      controlled trial.

PMID- 27048961
TI  - Understanding autism and other neurodevelopmental disorders through experimental
      translational neurobehavioral models.
AB  - Neurodevelopmental disorders (NDDs) are highly prevalent and severely
      debilitating brain illnesses caused by aberrant brain growth and development.
      Resulting in cognitive, social, motor, language and affective disabilities,
      common NDDs include autism spectrum disorder (ASD), intellectual disability,
      communication/speech disorders, motor/tic disorders and attention deficit
      hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and
      migration, synapse formation and myelination, aberrant neural development occurs
      over a substantial period of time. Genetic, epigenetic, and environmental factors
      play a key role in NDD pathogenesis. Animal models are an indispensable tool to
      study NDDs. Paralleling clinical findings, we comprehensively evaluate various
      preclinical tests and models which target key (social, cognitive, motor)
      neurobehavioral domains of ASD and other common NDDs. Covering both traditional
      (rodent) and alternative NDD models, we outline the emerging areas of research
      and emphasize how preclinical models play a key role in gaining translational and
      mechanistic insights into NDDs and their therapy.

PMID- 27048962
TI  - Can transcranial direct current stimulation counteract age-associated functional
      impairment?
AB  - Transcranial direct current stimulation (tDCS) can improve motor and cognitive
      function in young individuals and may be a viable tool to counteract age
      associated functional impairment. We review the growing body of research that
      investigated tDCS-effects in aging and attempt to provide a framework to guide
      future research in this emerging field. The majority of thirty reviewed studies
      (N=856 older participants) reported beneficial behavioral tDCS-effects across
      functional domains. Eleven studies included young and older adults and
      demonstrated that tDCS can restore impaired motor and cognitive functions.
      Several studies highlighted differences in the extent and timing of tDCS-effects
      between age-groups and the importance of mediating factors like baseline
      performance levels. Multi-session tDCS improved cognitive training outcome in two
      studies, however, limited transfer to untrained materials was reported. Montages
      inducing beneficial effects in young adults did not improve or even impaired
      performance in older adults in several studies. Thus, a cautious and more
      systematic approach that incorporates information about age-associated brain
      reorganization is advised when aiming to induce more permanent neuroplastic
      effects in older individuals in future studies.

PMID- 27048964
TI  - Relationship between virulence factors, resistance to antibiotics and
      phylogenetic groups of uropathogenic Escherichia coli in two locations in Mexico.
AB  - INTRODUCTION: Escherichia coli is the major causative agent of urinary tract
      infections (UTI), and virulence factors are responsible for the severity of these
      emerging infections. The aim of this study was to evaluate the relationship
      between virulence determinants and antibiotic susceptibility with phylogenetic
      groups of E.coli isolates of UTI in two locations in Mexico. METHODS: An analysis
      was performed on 50 isolates of E.coli from the centre of the country and 57 from
      a town in the southwest. The isolates were characterized by phenotype (serotyping
      assays, in vitro adhesion, biofilm formation, production of haemolysin, and
      antibiotic susceptibility) and genotype (phylogenetic groups and virulence
      genes). RESULTS: In the centre of the country location the phylogenetic group B2
      (60%) and F (12%) were significantly more prevalent and had a higher frequency of
      genes, fimH (96%), iutA (66%), sat (36%), compared to the southwest location,
      where the group A (35%) and B1 (21%) were significantly predominant and had fewer
      virulence genes. About one-fifth (21.5%) of all isolates belonged to the O25
      ST131 group. Haemolysin and biofilm producing strains were significantly higher
      in the southwest location. Resistance to ampicillin (92.5%), tetracycline
      (76.6%), and trimethoprim/sulfamethoxazole (70.1%) were the most common in both
      groups. CONCLUSION: The phylogenetic group, virulence factors, and antibiotic
      susceptibility of the E.coli that causes UTI in the community, varies
      significantly among the Mexican populations studied. Phylogenetic groups A and B1
      may be multidrug resistant and have the ability to produce UTI.

PMID- 27048966
TI  - Atlanto-axial infection after acupuncture.
AB  - A 67-year-old man presented with neck cellulitis following acupuncture for
      cervical spondylosis. Blood cultures were positive for methicillin-sensitive
      Staphylococcus aureus Increased neck pain and bacteraemia prompted MRI, which
      showed atlanto-axial septic arthritis without signs of infection of the tissues
      between the superficial cellulitic area and the atlanto-axial joint, thus making
      direct extension of infection unlikely. It is more likely that haematogenous
      spread of infection resulted in seeding in the atlanto-axial joint, with the
      proximity of the arthritis and acupuncture site being coincidental. Acupuncture
      is a treatment option for some indolent pain conditions. As such, acupuncture
      services are likely to be more frequently utilised. A history of acupuncture is
      rarely requested by the admitting doctor and seldom offered voluntarily by the
      patient, especially where the site of infection due to haematogenous spread is
      distant from the needling location. Awareness of infectious complications
      following acupuncture can reduce morbidity through early intervention.

PMID- 27048963
TI  - Endosomal system genetics and autism spectrum disorders: A literature review.
AB  - Autism spectrum disorders (ASDs) are a group of debilitating neurodevelopmental
      disorders thought to have genetic etiology, due to their high heritability. The
      endosomal system has become increasingly implicated in ASD pathophysiology. In an
      attempt to summarize the association between endosomal system genes and ASDs we
      performed a systematic review of the literature. We searched PubMed for relevant
      articles. Simons Foundation Autism Research Initiative (SFARI) gene database was
      used to exclude articles regarding genes with less than minimal evidence for
      association with ASDs. Our search retained 55 articles reviewed in two
      categories: genes that regulate and genes that are regulated by the endosomal
      system. Our review shows that the endosomal system is a novel pathway implicated
      in ASDs as well as other neuropsychiatric disorders. It plays a central role in
      aspects of cellular physiology on which neurons and glial cells are particularly
      reliant, due to their unique metabolic and functional demands. The system shows
      potential for biomarkers and pharmacological intervention and thus more research
      into this pathway is warranted.

PMID- 27048970
TI  - Diuretics for Hypertension: A Review and Update.
AB  - This review and update focuses on the clinical features of hydrochlorothiazide
      (HCTZ), the thiazide-like agents chlorthalidone (CTDN) and indapamide (INDAP),
      potassium-sparing ENaC inhibitors and aldosterone receptor antagonists, and loop
      diuretics. Diuretics are the second most commonly prescribed class of
      antihypertensive medication, and thiazide-related diuretics have increased at a
      rate greater than that of antihypertensive medications as a whole. The latest
      hypertension guidelines have underscored the importance of diuretics for all
      patients, but particularly for those with salt-sensitive and resistant
      hypertension. HCTZ is 4.2-6.2 systolic mm Hg less potent than CTDN, angiotensin
      converting enzyme inhibitors, beta blockers, and calcium channel blockers by 24
      hour measurements and 5.1mm Hg systolic less potent than INDAP by office
      measurements. For reducing cardiovascular events (CVEs), HCTZ is less effective
      than enalapril and amlodipine in randomized trials, and, in network analysis of
      trials, it is less effective than CTDN and HCTZ-amiloride. Combined with thiazide
      type diuretics, potassium-sparing agents decrease ventricular ectopy and reduce
      the risk for sudden cardiac death relative to thiazide-type diuretics used alone.
      A recent synthesis of 44 trials has shown that the relative potencies in
      milligrams among spironolactone (SPIR), amiloride, and eplerenone (EPLER) are
      approximately from 25 to 10 to 100, respectively, which may be important when
      SPIR is poorly tolerated. SPIR reduces proteinuria beyond that provided by other
      renin angiotensin aldosterone inhibitors. EPLER also reduces proteinuria and has
      beneficial effects on endothelial function. While guidelines often do not
      differentiate among specific diuretics, this review demonstrates that these
      distinctions are important for managing hypertension.

PMID- 27048969
TI  - Rnd3 as a Novel Target to Ameliorate Microvascular Leakage.
AB  - BACKGROUND: Microvascular leakage of plasma proteins is a hallmark of
      inflammation that leads to tissue dysfunction. There are no current therapeutic
      strategies to reduce microvascular permeability. The purpose of this study was to
      identify the role of Rnd3, an atypical Rho family GTPase, in the control of
      endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein
      delivery to ameliorate microvascular leakage was also investigated. METHODS AND
      RESULTS: Using immunofluorescence microscopy, Rnd3 was observed primarily in
      cytoplasmic areas around the nuclei of human umbilical vein endothelial cells.
      Permeability to fluorescein isothiocyanate-albumin and transendothelial
      electrical resistance of human umbilical vein endothelial cell monolayers served
      as indices of barrier function, and RhoA, Rac1, and Cdc42 activities were
      determined using G-LISA assays. Overexpression of Rnd3 significantly reduced the
      magnitude of thrombin-induced barrier dysfunction, and abolished thrombin-induced
      Rac1 inactivation. Depleting Rnd3 expression with siRNA significantly extended
      the time course of thrombin-induced barrier dysfunction and Rac1 inactivation.
      Time-lapse microscopy of human umbilical vein endothelial cells expressing GFP
      actin showed that co-expression of mCherry-Rnd3 attenuated thrombin-induced
      reductions in local lamellipodia that accompany endothelial barrier dysfunction.
      Lastly, a novel Rnd3 protein delivery method reduced microvascular leakage in a
      rat model of hemorrhagic shock and resuscitation, assessed by both intravital
      microscopic observation of extravasation of fluorescein isothiocyanate-albumin
      from the mesenteric microcirculation, and direct determination of solute
      permeability in intact isolated venules. CONCLUSIONS: The data suggest that Rnd3
      can shift the balance of RhoA and Rac1 signaling in endothelial cells. In
      addition, our findings suggest the therapeutic, anti-inflammatory potential of
      delivering Rnd3 to promote endothelial barrier recovery during inflammatory
      challenge.

PMID- 27048971
TI  - Direct visualization of biliary stricture through a colonoscope in a patient with
      Roux-en-Y hepaticojejunostomy.

PMID- 27048972
TI  - A novel "balloon/snare apparatus" technique to facilitate easy creation of
      fistula tract during EUS-guided gastroenterostomy.

PMID- 27048973
TI  - Improving the diagnostic yield of single-operator cholangioscopy-guided biopsy of
      indeterminate biliary strictures: ROSE to the rescue? (with video).
AB  - BACKGROUND AND AIMS: Tissue diagnosis, regardless of technique or endoscope used,
      can be challenging in patients with indeterminate biliary strictures (IDBSs).
      This exploratory study evaluated the utility and role of rapid onsite evaluation
      of touch imprint cytology (ROSE-TIC) when single-operator cholangioscopy (SOC)
      guided biopsies of IDBSs are performed. METHODS: Patients with IDBSs were
      evaluated by intraprocedural ROSE-TIC during SOC-guided biopsy procedures. Final
      diagnosis was established by long-term patient follow-up in conjunction with off
      site findings or surgical histology. The main outcome measure was to evaluate the
      utility of ROSE-TIC by determination of its operating characteristics and
      comparison with off-site histologic assessment. RESULTS: Of 31 patients with
      IDBSs, tissue diagnosis was indeterminate at prior ERCP-guided brush and/or
      biopsy in 14, prior EUS-guided FNA (EUS-FNA) in 6, and a mass could not be
      identified at EUS in 11. The mean number of biopsies performed was 3.3 (range 1
      8), and diagnostic interpretation by ROSE-TIC was diagnostic and/or suspicious
      for carcinoma in 15, benign in 13, atypical-reactive in 2, and bile duct
      intraductal papillary mucinous neoplasm in 1. Final diagnosis by surgical
      histology (n = 4), death by disease (n = 10), and patient follow-up (n = 17)
      showed that the overall sensitivity of ROSE-TIC for diagnosing malignancy was
      100%, specificity 88.9%, positive predictive value 86.7%, negative predictive
      value 100%, and diagnostic accuracy 93.5%. CONCLUSIONS: Preliminary data suggest
      that the diagnostic outcomes of SOC-guided biopsies in IDBSs can be significantly
      improved by using ROSE-TIC. This technique also may benefit centers that rely
      mainly on fluoroscopy-guided intraductal biopsies.

PMID- 27048974
TI  - Intraprocedural increase in heart rate during EUS-guided celiac plexus
      neurolysis: Clinically relevant or just a physiologic change?
AB  - BACKGROUND AND AIMS: Although EUS-guided celiac plexus neurolysis (EUS-CPN) is
      performed frequently for palliation of pain in pancreatic cancer, response to
      treatment is variable. Although intraprocedural increases in heart rate during
      alcohol injection are observed frequently, their significance and relationship to
      treatment outcome are unknown. The objective of this study was to examine whether
      a correlation exists between an increase in heart rate and treatment outcomes in
      patients undergoing EUS-CPN for pain relief in pancreatic cancer. METHODS: This
      is a prospective observational study of patients with abdominal pain caused by
      inoperable pancreatic cancer who underwent EUS-CPN. Heart rate change was defined
      as an increase of >=15 beats per minute (bpm) for >=30 seconds during alcohol
      injection. Main outcome measures were to compare pain, quality of life, opioid
      use, and survival between heart rate change and no-change groups. RESULTS: Heart
      rate change was observed in 25 of 51 patients (49.0%) who underwent EUS-CPN over
      a 12-month period. Although the heart rate change cohort had significantly better
      adjusted scores for pain (60 vs 73; P = .042) and components of quality of life
      such as nausea and/or vomiting (65 vs 81; P = .004), financial difficulties (41
      vs 57; P = .02), weight loss (45 vs 65; P = .007), and satisfaction with body
      image (52 vs 62; P = .035), there was no significant difference in postprocedural
      opioid use or survival between groups. CONCLUSIONS: Because patients with an
      increase in intraprocedural heart rate experienced significant improvement in
      pain and quality of life components, this observation must be further explored in
      order to improve the technique and outcomes of EUS-CPN.

PMID- 27048975
TI  - Effect of diphenyliodonium hexafluorophosphate on the physical and chemical
      properties of ethanolic solvated resins containing camphorquinone and 1-phenyl
      1,2-propanedione sensitizers as initiators.
AB  - OBJECTIVES: To evaluate the effects of the diphenyliodonium hexafluorophosphate
      (DPI) on the physical and mechanical properties of solvated dental adhesive
      resins containing camphorquinone (CQ) and/or 1-phenyl-1,2-propanedione (PPD) as
      initiators. METHODS: Model solvated resins containing bisphenol glycidyl
      methacrylate (BisGMA); triethyleneglycol dimethacrylate (TEGDMA); 1,3-glycerol
      dimethacrylate (GDMA); 2-hydroxyethyl methacrylate (HEMA); dimethylaminoethyl
      amine benzoate (EDAB) and ethanol were prepared. The resins were divided in 24
      test groups according to the incorporated initiator systems (CQ-0.5 or 1mol%; PPD
      0.5 or 1mol%; CQ+PPD-0.5 or 1mol%) as well the presence of DPI (0, 0.5 or 1mol%).
      Degree of conversion (using Fourier-transformed near infra-red spectroscopy),
      flexural strength and modulus by three point bending, cohesive strength and water
      sorption and solubility were measured. Data were statistically analyzed by one
      and two way ANOVA and Tukey's test (alpha=0.05). RESULTS: DPI increased the
      degree of conversion of all materials tested. Camphorquinone promoted higher
      degree of conversion than resins containing only PPD or CQ+PPD. Generally, the
      resins containing PPD+CQ with DPI presented higher flexural strength and modulus,
      cohesive strength, as well lower water sorption and solubility. SIGNIFICANCE: The
      use of PPD combined with CQ can increase the physical properties of the solvated
      resins. DPI improved the monomer conversion of all experimental materials and can
      positively modulate most of the physical properties of the solvated resins.

PMID- 27048976
TI  - Analytical performances of SPAPLUS(r) turbidimeter for the quantification of
      albumin and IgG in serum and cerebrospinal fluid.
AB  - OBJECTIVES: The intrathecal production of IgG is part of the diagnosis criteria
      for Multiple Sclerosis. Its assessment requires both quantitative (quantification
      of IgG and albumin in serum and cerebrospinal fluid (CSF)) and qualitative assays
      (isoelectric focusing). We have evaluated the analytical performances of the
      SPAPLUS(r) immunoturbidimeter (The Binding Site(r)) for the quantification of IgG
      and albumin in serum and CSF. DESIGN AND METHODS: Within-day and between-day
      precision, linearity and carry-over were assessed. Results obtained with
      SPAPLUS(r) were compared to those obtained with the nephelometer IMMAGE(r) 800,
      including albumin quotient and CSF IgG index. Isoelectric focusing was performed
      and considered as the gold standard for assessment of intrathecal production of
      IgG. RESULTS: The within-day and the between-day precisions were obtained at two
      concentration levels and were below the recommendations of the manufacturer and
      of the French Society of Clinical Biology. Our evaluation confirmed the linearity
      of the assays and the absence of contamination. An agreement above 94% was
      observed between the results obtained with SPAPLUS(r) and those obtained with
      IMMAGE(r) 800. The use of the new reference material DA470k did not significantly
      modify IgG and albumin values. The confrontation of CSF IgG index and isoelectric
      focusing results led to a sensitivity of 79% and a specificity of 97% of CSF IgG
      index quantified on SPAPLUS(r) for the presence of oligoclonal bands at IEF. The
      sensitivity of intrathecal IgG calculated with the Reiber's hyperbolic formula
      was 47.4% and specificity was 97% for the presence of oligoclonal bands at IEF.
      Automatic rerun managed by the device for concentrations outside the measuring
      range was satisfactory. CONCLUSION: The SPAPLUS(r) immunoturbidimeter displays
      good analytical performances for the parameters evaluated in this work.

PMID- 27048978
TI  - Near-UV photodissociation dynamics of CH2I2.
AB  - The near-UV photodissociation dynamics of CH2I2 has been investigated using a
      combination of velocity-map (slice) ion imaging and ab initio calculations
      characterizing the excited states. Ground state I((2)P3/2) and spin-orbit excited
      I*((2)P1/2) atoms were probed using 2 + 1 resonance-enhanced multiphoton
      ionization (REMPI) or with single-photon VUV ionization. Two-color ion images
      were recorded at pump wavelengths of 355 nm, 266 nm and 248 nm, and one-color ion
      images at the REMPI wavelengths of ~304 nm and ~280 nm. Analysis of the ion
      images shows that, regardless of iodine spin-orbit state, ~20% of the available
      energy is partitioned into translation E(T) at all excitation wavelengths
      indicating that the CH2I co-fragment is formed highly internally excited. The
      translational energy distributions comprise a slow, "statistical" component that
      peaks near zero and faster components that peak away from zero. The slow
      component makes an increasingly large contribution to the distribution as the
      excitation wavelength is decreased. The C-I bond dissociation energy of D0 =
      2.155 +/- 0.008 eV is obtained from the trend in the E(T) release of the faster
      components with increasing excitation energy. The I and I* ion images are
      anisotropic, indicating prompt dissociation, and are characterized by beta
      parameters that become increasingly positive with increasing E(T). The decrease
      in beta at lower translational energies can be attributed to deviation from axial
      recoil. MRCI calculations including spin-orbit coupling have been performed to
      identify the overlapping features in the absorption spectrum and characterize one
      dimensional cuts through the electronically excited potential energy surfaces.
      The excited states are of significantly mixed singlet and triplet character. At
      longer wavelengths, excitation directly accesses repulsive states primarily of B1
      symmetry, consistent with the observed <beta>, while shorter wavelengths accesses
      bound states, also of B1 symmetry that are crossed by repulsive states.

PMID- 27048977
TI  - How old is too old? Challenges faced by clinicians concerning age cutoffs for
      patients undergoing in vitro fertilization.
AB  - OBJECTIVE: To study how IVF providers view and make decisions concerning age
      cutoffs and futility (e.g., whether they establish clear cutoffs, and if so,
      where). DESIGN: In-depth interviews of approximately 1 hour. SETTING: Not
      applicable. PATIENT(S): Interviewees: 27 ART providers (17 physicians, 10 other
      providers) and 10 patients. INTERVENTION(S): Not applicable. MAIN OUTCOME
      MEASURE(S): Attitudes and decisions concerning age cutoffs were assessed.
      RESULT(S): Providers face several challenges and dilemmas concerning both the
      content and the process of decision-making about age cutoffs-what age cutoff to
      use for potential parents (women both using and not using their own eggs) and
      potential fathers (whether to consider the father's age, and if so, separately or
      only with the mother's age); what criteria to use in these decisions (how much to
      consider and weigh the mother's autonomy vs. the future child's well-being); how
      to make these decisions (e.g., "gut feelings" or perceptions of public opinion);
      who makes these decisions (e.g., physicians on their own vs. a formal ethics or
      Quality Assurance committee); and how to present/frame these issues to patients
      (e.g., how much to discourage older women). Patients' responses to age
      limitations vary (e.g., minimizing or feeling exceptions to the risks; or lying
      about their age). CONCLUSION(S): These data, the first to explore how providers
      make decisions about age cutoffs for patients, raise several critical issues.
      Although the American Society for Reproductive Medicine has addressed several
      concerns, the present data suggest additional questions and challenges, including
      inherent uncertainties and ethical conflicts, and have important implications for
      practice, policy, research, and education.

PMID- 27048979
TI  - Deletion of BMP receptor type IB decreased bone mass in association with
      compromised osteoblastic differentiation of bone marrow mesenchymal progenitors.
AB  - We previously found that disruption of two type I BMP receptors, Bmpr1a and
      Acvr1, respectively, in an osteoblast-specific manner, increased bone mass in
      mice. BMPR1B, another BMP type I receptor, is also capable of binding to BMP
      ligands and transduce BMP signaling. However, little is known about the function
      of BMPR1B in bone. In this study, we investigated the bone phenotype in Bmpr1b
      null mice and the impacts of loss of Bmpr1b on osteoblasts and osteoclasts. We
      found that deletion of Bmpr1b resulted in osteopenia in 8-week-old male mice, and
      the phenotype was transient and gender specific. The decreased bone mass was
      neither due to the changes in osteoblastic bone formation activity nor
      osteoclastic bone resorption activity in vivo. In vitro differentiation of Bmpr1b
      null osteoclasts was increased but resorption activity was decreased. Calvarial
      pre-osteoblasts from Bmpr1b mutant showed comparable differentiation capability
      in vitro, while they showed increased BMP-SMAD signaling in culture. Different
      from calvarial pre-osteoblasts, Bmpr1b mutant bone marrow mesenchymal progenitors
      showed compromised differentiation in vitro, which may be a reason for the
      osteopenic phenotype in the mutant mice. In conclusion, our results suggested
      that BMPR1B plays distinct roles from BMPR1A and ACVR1 in maintaining bone mass
      and transducing BMP signaling. 

PMID- 27048980
TI  - A systematic review and meta-analysis of low intensity CBT for psychosis.
AB  - Sixteen sessions of individual cognitive behavior therapy for people with
      psychosis (CBTp) is recommended. However, access to CBTp is poor, so the
      potential of low intensity CBTp (fewer than 16 sessions of face-to-face contact)
      is being explored. A systematic review and meta-analysis was conducted of 10
      controlled trials evaluating low intensity CBTp. Significant between-group
      effects were found on the primary outcome, symptoms of psychosis, at post
      intervention (d=-0.46, 95% CI: -0.06, -0.86) and follow-up (d=-0.40, 95% CI: 
      0.06, -0.74). Study quality did not moderate post-intervention psychosis
      outcomes, nor did contact time/number of sessions or therapy format (individual
      versus group). Between-group effects on secondary outcomes (depression, anxiety
      and functioning) were not significant at post-intervention, but became
      significant at follow-up for depression and functioning outcomes (but not for
      anxiety). Overall, findings suggest that low intensity CBTp shows promise with
      effect sizes comparable to those found in meta-analyses of CBTp more broadly. We
      suggest that low intensity CBTp could help widen access. Future research is
      called for to identify mechanisms of change and to ascertain moderators of
      outcome so that low intensity CBTp targets key mechanisms (so that scarce therapy
      time is used effectively) and so that interventions offered are matched to
      patient need.

PMID- 27048981
TI  - Effects of CO and CO2 on the desulfurization of H2S using a ZnO sorbent: a
      density functional theory study.
AB  - The density functional theory (DFT) method has been performed to study the
      effects of CO and CO2 on the desulfurization of H2S over a ZnO sorbent. It shows
      that COS is inevitably formed on the ZnO(101-0) surface, which tends to be
      adsorbed onto the surface via a S-C bond binding with either a long or a short Zn
      O bond. Potential energy profiles for the COS formation via reactions between H2S
      and CO, and H2S and CO2 on the ZnO(101-0) surface have been constructed. In the
      presence of CO, the dissociated active S of H2S reacting with CO leads to the
      formation of COS, and the activation energy of the rate-determining step is 87.7
      kJ mol(-1). When CO2 is present, the linear CO2 is first transferred to active
      CO2 in a triplet state, and then combines with active S to form COS with the
      highest energy barrier of 142.4 kJ mol(-1). Rate constants at different
      temperatures show that the formation of COS via the reaction of CO and H2S is
      easier than that of CO2 and H2S over the ZnO surface.

PMID- 27048982
TI  - Synthesis of oxime-based CO-releasing molecules, CORMs and their immobilization
      on maghemite nanoparticles for magnetic-field induced CO release.
AB  - Oxime-based CO-releasing molecules (oximeCORMs) were immobilized with a catechol
      modified backbone on maghemite iron oxide nanoparticles (IONPs) to give
      oximeCORM@IONP. The CO release from the free and immobilized oximeCORMs was
      measured using the standard myoglobin assay. The oximeCORM-nanoparticles were
      coated with dextran for improved water solubility and confined into an alginate
      shell for protection and separation from the surrounding myoglobin assay to allow
      for CO release studies by UV/Vis absorption without interference from highly
      absorptive oximeCORM@IONP. Half-lifes of the oxime-based polymer-confined
      alginate@dextran@oximeCORM@IONPs were estimated at 20  degrees C to 814 +/- 23
      min, at 37  degrees C to 346 +/- 83 min and at 50  degrees C to 73 +/- 1 min. The
      alginate@dextran@oximeCORM@IONP composite showed a further decrease of the half
      life of CO release to 153 +/- 27 min at 37  degrees C through local magnetic
      heating of the susceptible iron oxide nanoparticles with application of an
      external alternating magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mTesla). The
      activation energy for the CO release from molecular dicarbonylchlorido(imidazole
      2-carbaldehydeoxime)(alkoxycarbonyl)ruthenium(ii) complexes is determined to be
      ~100 kJ mol(-1) for five different imidazole-oxime derivatives.

PMID- 27048983
TI  - MBPpred: Proteome-wide detection of membrane lipid-binding proteins using profile
      Hidden Markov Models.
AB  - A large number of modular domains that exhibit specific lipid binding properties
      are present in many membrane proteins involved in trafficking and signal
      transduction. These domains are present in either eukaryotic peripheral membrane
      or transmembrane proteins and are responsible for the non-covalent interactions
      of these proteins with membrane lipids. Here we report a profile Hidden Markov
      Model based method capable of detecting Membrane Binding Proteins (MBPs) from
      information encoded in their amino acid sequence, called MBPpred. The method
      identifies MBPs that contain one or more of the Membrane Binding Domains (MBDs)
      that have been described to date, and further classifies these proteins based on
      their position in respect to the membrane, either as peripheral or transmembrane.
      MBPpred is available online at http://bioinformatics.biol.uoa.gr/MBPpred. This
      method was applied in selected eukaryotic proteomes, in order to examine the
      characteristics they exhibit in various eukaryotic kingdoms and phyla. 

PMID- 27048984
TI  - The centre of rotation of the shoulder complex and the effect of normalisation.
AB  - Shoulder motions consist of a composite movement of three joints and one pseudo
      joint, which together dictate the humerothoracic motion. The purpose of this work
      was to quantify the location of the centre of rotation (CoR) of the shoulder
      complex as a whole. Dynamic motion of 12 participants was recorded using optical
      motion tracking during coronal, scapular and sagittal plane elevation. The
      instantaneous CoR was found for each angle of elevation using helical axes
      projected onto the three planes of motion. The location of an average CoR for
      each plane was evaluated using digitised and anthropometric measures for
      normalisation. When conducting motion in the coronal, scapular, and sagittal
      planes, respectively, the coefficients for locating the CoRs of the shoulder
      complex are -61%, -61%, and -65% of the anterior-posterior dimension - the vector
      between the midpoint of the incisura jugularis and the xiphoid process and the
      midpoint of the seventh cervical vertebra and the eighth thoracic vertebra; 0%, 
      1%, and -2% of the superior-inferior dimension - the vector between the midpoint
      of the acromioclavicular joints and the midpoint of the anterior superior iliac
      spines; and 57%, 57%, and 78% of the medial-lateral dimension -0.129 times the
      height of the participant. Knowing the location of the CoR of the shoulder
      complex as a whole enables improved participant positioning for evaluation and
      rehabilitation activities that involve movement of the hand with a fixed radius,
      such as those that employ isokinetic dynamometers.

PMID- 27048985
TI  - Correction: Aromatic cages B420/+: unprecedented existence of octagonal holes in
      boron clusters.
AB  - Correction for 'Aromatic cages B42(0/+): unprecedented existence of octagonal
      holes in boron clusters' by Truong Ba Tai et al., Phys. Chem. Chem. Phys., 2016,
      DOI: 10.1039/c5cp07342a.

PMID- 27048986
TI  - MIR retroposon exonization promotes evolutionary variability and generates
      species-specific expression of IGF-1 splice variants.
AB  - Insulin-like growth factor (IGF) -1 is a pleiotropic hormone exerting mitogenic
      and anti-apoptotic effects. Inclusion or exclusion of exon 5 into the IGF-1 mRNA
      gives rise to three transcripts, IGF-1Ea, IGF-1Eb and IGF-1Ec, which yield three
      different C-terminal extensions called Ea, Eb and Ec peptides. The biological
      significance of the IGF-1 splice variants and how the E-peptides affect the
      actions of mature IGF-1 are largely unknown. In this study we investigated the
      origin and conservation of the IGF-1 E-peptides and we compared the pattern of
      expression of the IGF-1 isoforms in vivo, in nine mammalian species, and in vitro
      using human and mouse IGF-1 minigenes. Our analysis showed that only IGF-1Ea is
      conserved among all vertebrates, whereas IGF-1Eb and IGF-1Ec are an evolutionary
      novelty originated from the exonization of a mammalian interspersed repetitive-b
      (MIR-b) element. Both IGF-1Eb and IGF-1Ec mRNAs were constitutively expressed in
      all mammalian species analyzed but their expression ratio varies greatly among
      species. Using IGF-1 minigenes we demonstrated that divergence in cis-acting
      regulatory elements between human and mouse conferred species-specific features
      to the exon 5 region. Finally, the protein-coding sequences of exon 5 showed low
      rate of synonymous mutations and contain disorder-promoting amino acids,
      suggesting a regulatory role for these domains. In conclusion, exonization of a
      MIR-b element in the IGF-1 gene determined gain of exon 5 during mammalian
      evolution. Alternative splicing of this novel exon added new regulatory elements
      at the mRNA and protein level potentially able to regulate the mature IGF-1
      across tissues and species. 

PMID- 27048987
TI  - A digital microfluidic interface between solid-phase microextraction and liquid
      chromatography-mass spectrometry.
AB  - We introduce a method to couple solid-phase microextraction (SPME) with HPLC-MS
      using digital microfluidics (DMF). In the new system, SPME fibers are used to
      extract analytes from complex sample solutions, after which the analytes are
      desorbed into solvent droplets in a DMF device. The open geometry of DMF allows
      straightforward insertion of SPME fibers without requiring a complicated
      interface, and automated droplet manipulation enables multiplexed processing of
      the fibers. In contrast to other multiplexed SPME elution interfaces, the low
      volumes inherent to DMF allow for pre-concentration of analytes prior to
      analysis. The new SPME-DMF-HPLC-MS method was applied to the quantification of
      pg/mL-level free steroid hormones in urine. We propose that this new method will
      be useful for a wide range of applications requiring cleanup and pre
      concentration with convenient coupling to high-performance analytical techniques.

PMID- 27048988
TI  - STAND: Surface Tension for Aggregation Number Determination.
AB  - Taking advantage of the extremely high dependence of surface tension on the
      concentration of amphiphilic molecules in aqueous solution, a new model based on
      the double equilibrium between free and aggregated molecules in the liquid phase
      and between free molecules in the liquid phase and those adsorbed at the
      air/liquid interface is presented and validated using literature data and
      fluorescence measurements. A key point of the model is the use of both the
      Langmuir isotherm and the Gibbs adsorption equation in terms of free molecules
      instead of the nominal concentration of the solute. The application of the model
      should be limited to non ionic compounds since it does not consider the presence
      of counterions. It requires several coupled nonlinear fittings for which we
      developed a software that is publicly available in our server as a web
      application. Using this tool, it is straightforward to get the average
      aggregation number of an amphiphile, the micellization free energy, the
      adsorption constant, the maximum surface excess (and so the minimum area per
      molecule), the distribution of solute in the liquid phase between free and
      aggregate species, and the surface coverage in only a couple of seconds, just by
      uploading a text file with surface tension vs concentration data and the
      corresponding uncertainties.

PMID- 27048989
TI  - Formation of Polyion Complex (PIC) Micelles and Vesicles with Anionic pH
      Responsive Unimer Micelles and Cationic Diblock Copolymers in Water.
AB  - A random copolymer (p(A/MaU)) of sodium 2-(acrylamido)-2-methylpropanesulfonate
      (AMPS) and sodium 11-methacrylamidoundecanate (MaU) was prepared via conventional
      radical polymerization, which formed a unimer micelle under acidic conditions due
      to intramolecular hydrophobic interactions between the pendant undecanoic acid
      groups. Under basic conditions, unimer micelles were opened up to an expanded
      chain conformation by electrostatic repulsion between the pendant sulfonate and
      undecanoate anions. A cationic diblock copolymer (P163M99) consisting of poly(3
      (methacrylamido)propyl)trimethylammonium chloride (PMAPTAC) and hydrophilic
      polybetaine, 2-(methacryloyloxy)ethylphosphorylcholine (MPC), blocks was prepared
      via controlled radical polymerization. Mixing of p(A/MaU) and P163M99 in 0.1 M
      aqueous NaCl under acidic conditions resulted in the formation of spherical
      polyion complex (PIC) micelles and vesicles, depending on polymer concentration
      before mixing. Shapes of the PIC micelles and vesicles changed under basic
      conditions due to collapse of the charge balance between p(A/MaU) and P163M99.
      The PIC vesicles can incorporate nonionic hydrophilic guest molecules, and the
      PIC micelles and vesicles can accept hydrophobic guest molecules in the
      hydrophobic core formed from p(A/MaU).

PMID- 27048990
TI  - Governance, organization, accountability and sustainability of a region-wide
      school-based deworming program in Loreto, Peru.
AB  - Chau Cuica was the name given by the regional government of Loreto in Peru for
      its school-based deworming program which was initiated in 2012 with a donation of
      mebendazole from an international non-governmental organization. Embedded in the
      program from the start was a sentinel surveillance component which consisted of
      16 sentinel schools representing Loreto's seven provinces. Coverage rates varied
      between 35% and 61% over the first two years of the program (and seven deworming
      cycles). Initial prevalences of soil-transmitted helminth infections were high,
      with 82.4% of schoolchildren having at least one infection and prevalences of
      both Ascaris lumbricoides and Trichuris trichiura infections both exceeding 60%.
      After two years, these prevalences had dropped to 56% for any STH infection, 38%
      for A. lumbricoides and 34% for T. trichiura. Importantly, the proportions of
      children with moderate and heavy infections also dropped. Both the regional
      Ministry of Health and the Ministry of Education were jointly charged to
      implement this deworming program. The program's costs were estimated to be
      approximately 22 cents (USD) per child per deworming cycle. The responsibility
      for the surveillance component was initially undertaken by research partners from
      a local NGO and a Canadian university, which transferred gradually over the
      course of the deworming program to being entirely the responsibility of the
      Ministry of Health. This regional deworming program may serve as a model for
      other jurisdictions that are planning a school-based deworming program with an
      integrated surveillance component to monitor impact. 

PMID- 27048991
TI  - Bovine Serum Albumin Adsorption in Mesoporous Titanium Dioxide: Pore Size and
      Pore Chemistry Effect.
AB  - Understanding the mechanism of protein adsorption and designing materials with
      high sensitivity, high specificity and fast response are critical to develop the
      next-generation biosensing and diagnostic platforms. Mesoporous materials with
      high surface area, tunable pores, and good thermal/hydrostatic stabilities are
      promising candidates in this field. Because of the excellent biocompatibility,
      titanium dioxide has received an increasing interest in the past decade for
      biomedical applications. In this work, we synthesized mesoporous titanium dioxide
      with controlled pore sizes (7.2-28.0 nm) and explored their application for
      bovine serum albumin (BSA) adsorption. Scanning electron microscopy (SEM), X-ray
      powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and
      nitrogen adsorption/desorption experiments were performed to characterize the
      mesoporous TiO2 samples before and after BSA adsorption. Isothermal
      microcalorimetry was applied to measure both the adsorption heat and conformation
      rearrangement heat of BSA in those mesopores. We also carried out
      thermogravimetry measurements to qualitatively estimate the concentration of
      hydroxyl groups, which plays an important role in stabilizing BSA in-pore
      adsorption. The adsorption stability was also examined by leaching experiments.
      The results showed that TiO2 mesopores can host BSA adsorption when their
      diameters are larger than the hydrodynamic size of BSA (~9.5 nm). In larger
      mesopores studied, two BSA molecules were adsorbed in the same pores. In contrast
      to the general understanding that large mesopores demonstrate poor stabilities
      for protein adsorptions, the synthesized mesoporous TiO2 samples demonstrated
      good leaching stabilities for BSA adsorption. This is probably due to the
      combination of the mesoporous confinement and the in-pore hydroxyl groups.

PMID- 27048992
TI  - Fiber-optic Raman spectroscopy for in vivo diagnosis of gastric dysplasia.
AB  - This study aims to assess the clinical utility of a rapid fiber-optic Raman
      spectroscopy technique developed for enhancing in vivo diagnosis of gastric
      precancer during endoscopic examination. We have developed a real-time fiber
      optic Raman spectroscopy system capable of simultaneously acquiring both
      fingerprint (FP) (i.e., 800-1800 cm(-1)) and high-wavenumber (HW) (i.e., 2800
      3600 cm(-1)) Raman spectra from gastric tissue in vivo at endoscopy. A total of
      5792 high-quality in vivo FP/HW Raman spectra (normal (n = 5160); dysplasia (n =
      155), and adenocarcinoma (n = 477)) were acquired in real-time from 441 tissue
      sites (normal (n = 396); dysplasia (n = 11), and adenocarcinoma (n = 34)) of 191
      gastric patients (normal (n = 172); dysplasia (n = 6), and adenocarcinoma (n =
      13)) undergoing routine endoscopic examinations. Partial least squares
      discriminant analysis (PLS-DA) together with leave-one-patient-out cross
      validation (LOPCV) were implemented to develop robust spectral diagnostic models.
      The FP/HW Raman spectra differ significantly between normal, dysplasia and
      adenocarcinoma of the stomach, which can be attributed to changes in proteins,
      lipids, nucleic acids, and the bound water content. PLS-DA and LOPCV show that
      the fiber-optic FP/HW Raman spectroscopy provides diagnostic sensitivities of
      96.0%, 81.8% and 88.2%, and specificities of 86.7%, 95.3% and 95.6%,
      respectively, for the classification of normal, dysplastic and cancerous gastric
      tissue, superior to either the FP or HW Raman techniques alone. Further
      dichotomous PLS-DA analysis yields a sensitivity of 90.9% (10/11) and specificity
      of 95.9% (380/396) for the detection of gastric dysplasia using FP/HW Raman
      spectroscopy, substantiating its clinical advantages over white light reflectance
      endoscopy (sensitivity: 90.9% (10/11), and specificity: 51.0% (202/396)). This
      work demonstrates that the fiber-optic FP/HW Raman spectroscopy technique has
      great promise for enhancing in vivo diagnosis of gastric precancer during routine
      endoscopic examination.

PMID- 27048993
TI  - Hybrid nanostructures of metal/two-dimensional nanomaterials for plasmon-enhanced
      applications.
AB  - Hybrid nanostructures composed of graphene or other two-dimensional (2D)
      nanomaterials and plasmonic metal components have been extensively studied. The
      unusual properties of 2D materials are associated with their atomically thin
      thickness and 2D morphology, and many impressive structures enable the metal
      nanomaterials to establish various interesting hybrid nanostructures with
      outstanding plasmonic properties. In addition, the hybrid nanostructures display
      unique optical characteristics that are derived from the close conjunction of
      plasmonic optical effects and the unique physicochemical properties of 2D
      materials. More importantly, the hybrid nanostructures show several plasmonic
      electrical effects including an improved photogeneration rate, efficient carrier
      transfer, and a plasmon-induced "hot carrier", playing a significant role in
      enhancing device performance. They have been widely studied for plasmon-enhanced
      optical signals, photocatalysis, photodetectors (PDs), and solar cells. In this
      review, the developments in the field of metal/2D hybrid nanostructures are
      comprehensively described. Preparation of hybrid nanostructures is first
      presented according to the 2D material type, as well as the metal nanomaterial
      morphology. The plasmonic properties and the enabled applications of the hybrid
      nanostructures are then described. Lastly, possible future research in this
      promising field is discussed.

PMID- 27048994
TI  - Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin
      family protein.
AB  - Lysenin from the coelomic fluid of the earthworm Eisenia fetida belongs to the
      aerolysin family of small beta-pore-forming toxins (beta-PFTs), some members of
      which are pathogenic to humans and animals. Despite efforts, a high-resolution
      structure of a channel for this family of proteins has been elusive and therefore
      the mechanism of activation and membrane insertion remains unclear. Here we
      determine the pore structure of lysenin by single particle cryo-EM, to 3.1 A
      resolution. The nonameric assembly reveals a long beta-barrel channel spanning
      the length of the complex that, unexpectedly, includes the two pre-insertion
      strands flanking the hypothetical membrane-insertion loop. Examination of other
      members of the aerolysin family reveals high structural preservation in this
      region, indicating that the membrane-insertion pathway in this family is
      conserved. For some toxins, proteolytic activation and pro-peptide removal will
      facilitate unfolding of the pre-insertion strands, allowing them to form the beta
      barrel of the channel. 

PMID- 27048995
TI  - In vivo MRI based prostate cancer localization with random forests and auto
      context model.
AB  - Prostate cancer is one of the major causes of cancer death for men. Magnetic
      resonance (MR) imaging is being increasingly used as an important modality to
      localize prostate cancer. Therefore, localizing prostate cancer in MRI with
      automated detection methods has become an active area of research. Many methods
      have been proposed for this task. However, most of previous methods focused on
      identifying cancer only in the peripheral zone (PZ), or classifying suspicious
      cancer ROIs into benign tissue and cancer tissue. Few works have been done on
      developing a fully automatic method for cancer localization in the entire
      prostate region, including central gland (CG) and transition zone (TZ). In this
      paper, we propose a novel learning-based multi-source integration framework to
      directly localize prostate cancer regions from in vivo MRI. We employ random
      forests to effectively integrate features from multi-source images together for
      cancer localization. Here, multi-source images include initially the multi
      parametric MRIs (i.e., T2, DWI, and dADC) and later also the iteratively
      estimated and refined tissue probability map of prostate cancer. Experimental
      results on 26 real patient data show that our method can accurately localize
      cancerous sections. The higher section-based evaluation (SBE), combined with the
      ROC analysis result of individual patients, shows that the proposed method is
      promising for in vivo MRI based prostate cancer localization, which can be used
      for guiding prostate biopsy, targeting the tumor in focal therapy planning,
      triage and follow-up of patients with active surveillance, as well as the
      decision making in treatment selection. The common ROC analysis with the AUC
      value of 0.832 and also the ROI-based ROC analysis with the AUC value of 0.883
      both illustrate the effectiveness of our proposed method.

PMID- 27048996
TI  - Effect of peripheral circadian dysfunction on metabolic disease in response to a
      diabetogenic diet.
AB  - BMAL1 is a core component of the transcription/translation machinery that
      regulates central and peripheral circadian rhythms that coordinate behavior and
      metabolism, respectively. Our objective was to determine the impact of BMAL1 in
      adipose alone or in combination with liver on metabolic phenotypes. Control,
      adipose-Bmal1 knockout (ABKO), and liver- and adipose-Bmal1 knockout (LABKO)
      female mice were placed in TSE System metabolic chambers for metabolic
      phenotyping. A second cohort of male mice was fed a control or diabetogenic diet,
      and body weight and composition, glucose tolerance, insulin sensitivity, and
      serum and hepatic lipids were measured. Both female ABKO and LABKO mice exhibited
      increased food consumption compared with control mice. ABKO mice also exhibited
      increased overall activity predominantly during the light phase compared with
      both control and LABKO mice and were protected from increased weight gain. When
      the male cohort was challenged with a diabetogenic diet, LABKO mice had increased
      body weight due to increased fat mass compared with control and ABKO mice.
      However, these mice did not present further impairments in glycemic control,
      adipose inflammation, or liver injury. LABKO mice had increased hepatic
      cholesterol and elevated expression of cholesterol synthesis and uptake genes.
      Our data indicate that deletion of this allele in adipose or in combination with
      liver alters feeding behavior and locomotor activity. However, obesity is
      exacerbated only with the combination of liver and adipose deletion.

PMID- 27048998
TI  - Response of Pigment Epithelial Detachment to Anti-Vascular Endothelial Growth
      Factor Treatment in Age-Related Macular Degeneration.
AB  - OBJECTIVE: To evaluate the therapeutic response of pigment epithelial detachment
      (PED) to anti-vascular endothelial growth factor (VEGF) treatment in neovascular
      age-related macular degeneration (nAMD), and identify predictive factors for PED
      resolution after treatment. DESIGN: Retrospective, interventional case series.
      METHODS: A total of 202 treatment-naive nAMD eyes presenting PED at baseline were
      retrospectively included and analyzed. All patients were treated with an initial
      series of 3 monthly loading injections of ranibizumab or aflibercept, followed by
      additional injections as required. RESULTS: After 12 months of treatment, the
      mean PED height decreased from 453 +/- 261 MUm at baseline to 230 +/- 142 MUm (P
      = .002), and the mean best-corrected visual acuity improved from 0.71 +/- 0.41
      logarithm of the minimal angle of resolution (Snellen equivalent, 20/102) to 0.60
      +/- 0.36 (20/79) (P = .024). The proportion of complete PED resolution after
      treatment was 19.3% (39 eyes). Multivariate logistic regression analysis was used
      to find baseline characteristics associated with a higher chance of PED
      resolution, including lower PED height at baseline (P = .018), polypoidal
      choroidal vasculopathy (P = .015), or retinal angiomatous proliferation (P =
      .010) compared to typical nAMD; serous PED (P = .022) compared to fibrovascular
      PED; and aflibercept (P = .039) compared to ranibizumab. CONCLUSIONS: PEDs
      secondary to nAMD showed significant functional and anatomic improvement after
      intravitreal anti-VEGF injections over 12 months. However, the anti-VEGF
      treatment showed limited efficacy for the complete resolution of PED. The PED
      type, nAMD subtype, baseline PED height, and anti-VEGF drug type was associated
      with a higher probability of PED resolution after treatment.

PMID- 27048997
TI  - SERMs have substance-specific effects on bone, and these effects are mediated via
      ERalphaAF-1 in female mice.
AB  - The bone-sparing effect of estrogens is mediated primarily via estrogen receptor
      (ER)alpha, which stimulates gene transcription through activation function (AF)-1
      and AF-2. The role of ERalphaAF-1 for the estradiol (E2) effects is tissue
      specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene
      (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis.
      They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but
      not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the
      tissue specificity of Ral, Las, and Bza and evaluated the role of ERalphaAF-1 for
      the effects of these SERMs, with an emphasis on bone parameters. We treated
      ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERalphaAF-1
      (ERalphaAF-1(0)) with E2, Ral, Las, or Bza. All three SERMs increased trabecular
      bone mass in the axial skeleton. In the appendicular skeleton, only Las increased
      the trabecular bone volume/tissue volume and trabecular number, whereas both Ral
      and Las increased the cortical bone thickness and strength. However, Ral also
      increased cortical porosity. The three SERMs had only a minor effect on uterine
      weight. Notably, all evaluated effects of these SERMs were absent in ovx
      ERalphaAF-1(0) mice. In conclusion, all SERMs had similar effects on axial bone
      mass. However, the SERMs had slightly different effects on the appendicular
      skeleton since only Las increased the trabecular bone mass and only Ral increased
      the cortical porosity. Importantly, all SERM effects require a functional
      ERalphaAF-1 in female mice. These results could lead to development of more
      specific treatments for osteoporosis.

PMID- 27048999
TI  - Endophthalmitis Caused by Nontuberculous Mycobacterium: Clinical Features,
      Antimicrobial Susceptibilities, and Treatment Outcomes.
AB  - PURPOSE: To report the clinical features, antibiotic susceptibilities and
      treatment outcomes in patients with endophthalmitis caused by nontuberculous
      mycobacterium. DESIGN: Noncomparative, consecutive case series. METHODS:
      Retrospective chart review between December 1990 and June 2014. RESULTS: In the
      19 study patients, the clinical setting of endophthalmitis included post-cataract
      surgery (7/19, 36.8%), post-glaucoma implant (6/19, 31.6%), post-intravitreal
      injection (2/19, 10.5%), endogenous endophthalmitis (2/19, 10.5%), post-pars
      plana vitrectomy (1/19, 5.3%), and post-scleral buckle exposure (1/19, 5.3%).
      Chronic recurrent or persisting ocular inflammation was present in 15 of 19
      patients (78.9%). The species isolated were Mycobacterium chelonae in 14 patients
      (73.7%), M fortuitum in 3 patients (15.8%), M triplex in 1 patient (5.3%), and M
      avium intracellulare in 1 patient (5.3%). Antibiotic susceptibilities to tested
      isolates were the following: amikacin (14/16; 87.5%) and clarithromycin (12/16,
      75.0%). Intravitreal injections of amikacin (0.4 mg/0.1 mL) were given in 14 of
      19 patients (73.7%) with an average of 7 injections per patient (range, 1-24
      injections). Intraocular lens removal was performed for 6 of 7 patients (85.7%)
      with post-cataract surgery endophthalmitis. All the patients with glaucoma
      implant (6/6, 100%) underwent implant removal. At last follow-up, 6 of 19
      patients (31.6%) had best-corrected visual acuity of 20/400 or better.
      CONCLUSION: Endophthalmitis caused by nontuberculous mycobacterium often included
      chronic recurrent or persistent intraocular inflammation and frequently required
      removal of ocular device (intraocular lens, glaucoma implant, or scleral buckle).
      The majority of the isolates were susceptible to amikacin and clarithromycin.
      Visual outcomes in these patients even after treatment were generally poor.

PMID- 27049001
TI  - Inhibitory Performance Predicting Drinking Behaviours Among Young Adults.
AB  - AIMS: While inhibition has been studied extensively in correlation to alcohol
      abuse within the adult population, it has been studied less so in relation to the
      alcohol consumption habits of young adults. Accordingly, this is the first study
      with the objective of identifying which subcomponent(s) of inhibitory
      performance, behaviourally measured by the withholding of a pre-potent response,
      the cancellation of a pre-potent response and interference inhibition will best
      predict binge drinking habits among young adults. METHODS: Forty-nine collegiate
      adults (41 females) with a mean age of 21.92 +/- 1.34 years, performed three
      cognitive batteries assessing inhibition: Stop Signal task (SST), Go/No-Go task
      (GNG) and Simon task. Participants completed two biweekly alcohol logs, 2 and 4
      weeks following inhibitory assessment. RESULTS: Regression analysis revealed that
      interference inhibition (Simon task) and/or withholding inhibition (GNG)
      contributed to the prediction of total intoxication days and total hangover days.
      CONCLUSION: These findings suggest that specific subcomponents of response
      inhibition, and not others, are more suitable for predicting alcohol consumption
      habits.

PMID- 27049000
TI  - Long-Term Results of Pro Re Nata Regimen of Aflibercept Treatment in Persistent
      Neovascular Age-Related Macular Degeneration.
AB  - PURPOSE: To determine the 24-month results of patients who had pro re nata (PRN)
      aflibercept treatment owing to recurrent or resistant neovascular macular
      degeneration. DESIGN: Retrospective, interventional, consecutive case series.
      METHODS: Eighty-one eyes of 78 patients with resistant or multiple recurrences of
      intraretinal or subretinal fluid while receiving monthly bevacizumab or
      ranibizumab injections and were switched to strict, as-needed aflibercept
      treatment with every-8-weeks spectral-domain optical coherence tomography (SDOCT)
      guided monitoring were included. If there was a persistence of fluid despite this
      treatment, more frequent aflibercept injections were considered. Anatomic
      outcomes including maximum retinal thickness, central macular thickness, maximum
      pigment epithelial detachment height, maximum fluid height, and visual acuity
      (VA) were assessed at given follow-ups. RESULTS: All anatomic endpoints
      significantly improved following 3 consecutive aflibercept injections, which were
      maintained through 24 months (P < .05 for all endpoints at all visits). Thirty
      seven eyes (45.6%) required more frequent injections with monthly SDOCT-guided
      monitoring at a median of 37 weeks (interquartile range, 30-62 weeks) to
      adequately treat the retinal fluid. Seventy-one of 81 eyes (87.7%) became
      completely dry on at least 1 follow-up visit; however, there was no significant
      improvement in VA during the study period. CONCLUSION: Aflibercept injection with
      an as-needed regimen was effective in many eyes previously treated with monthly
      bevacizumab or ranibizumab injections that had persistent or recurrent fluid.
      Despite significant improvement in anatomic outcomes, vision remained stable
      throughout the 2-year follow-up, likely because this cohort of patients had
      advanced choroidal neovascular membrane upon enrollment (recurrent or resistant).

PMID- 27049002
TI  - Risk Factors for Neonatal Arterial Ischemic Stroke: The Importance of the
      Intrapartum Period.
AB  - OBJECTIVE: To investigate risk factors for neonatal arterial ischemic stroke
      (NAIS), and compare them with those present in term controls and infants with
      hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Antepartum and intrapartum
      data were collected at presentation from 79 infants with NAIS and compared with
      239 controls and 405 infants with HIE. The relationships between risk factors and
      NAIS were explored using univariable and multivariable regression. RESULTS:
      Compared with controls, infants with NAIS more frequently had a family history of
      seizures/neurologic diseases, primiparous mothers, and male sex. Mothers of
      infants with NAIS experienced more intrapartum complications: prolonged rupture
      of membranes (21% vs 2%), fever (14% vs 3%), thick meconium (25% vs 7%),
      prolonged second stage (31% vs 13%), tight nuchal cord (15% vs 6%), and abnorm8al
      cardiotocography (67% vs 21%). Male sex (OR 2.8), family history of seizures (OR
      6.5) or neurologic diseases (OR 4.9), and >=1 (OR 5.8) and >=2 (OR 21.8)
      intrapartum complications were independently associated with NAIS. Infants with
      NAIS and HIE experienced similar rates though different patterns of intrapartum
      complications. Maternal fever, prolonged rupture of membranes, prolonged second
      stage, tight nuchal cord, and failed ventouse delivery were more common in NAIS;
      thick meconium, sentinel events, and shoulder dystocia were more frequent in HIE.
      Abnormal cardiotocography occurred in 67% of NAIS and 77.5% of infants with HIE.
      One infant with NAIS and no infant with HIE was delivered by elective cesarean
      (10% of controls). CONCLUSIONS: NAIS is multifactorial in origin and shares risk
      factors in common with HIE. Intrapartum events may play a more significant role
      in the pathogenesis of NAIS than previously recognized.

PMID- 27049003
TI  - Walking on a mental time line: Temporal processing affects step movements along
      the sagittal space.

PMID- 27049005
TI  - Is asthma overdiagnosed?

PMID- 27049004
TI  - Syringe Stockpiling by Persons Who Inject Drugs: An Evaluation of Current
      Measures for Needle and Syringe Program Coverage.
AB  - Needle and syringe program (NSP) coverage is commonly used to assess NSP
      effectiveness. However, existing measures don't capture whether persons who
      inject drugs (PWIDs) stockpile syringes, an important and novel aspect of NSP
      coverage. In this study, we determine the extent of stockpiling in a sample of
      Australian PWIDs and assess whether including stockpiling enhances NSP coverage
      measures. As part of the Illicit Drug Reporting System study, PWIDs reported
      syringes procured and given away, total injections in the last month, and
      syringes currently stockpiled in 2014. We calculated NSP coverage with and
      without stockpiling to determine proportional change in adequate NSP coverage. We
      conducted receiver operating characteristic curve analysis to determine whether
      inclusion of stockpiled syringes in the measure improved sensitivity in
      discriminating cases and noncases of risky behaviors. Three-quarters of the
      sample reported syringe stockpiling, and stockpiling was positively associated
      with nonindigenous background, stable accommodation, no prison history, longer
      injecting careers, and more frequent injecting. Compared with previous measures,
      our measure was significantly better at discriminating cases of risky behaviors.
      Our results could inform NSP policy to loosen restricted-exchange practice,
      allowing PWIDs greater flexibility in syringe procurement practices, promoting
      greater NSP coverage, and reducing PWIDs' engagement in risky behaviors.

PMID- 27049006
TI  - K2Sn2ZnSe6, Na2Ge2ZnSe6, and Na2In2GeSe6: a new series of quaternary selenides
      with intriguing structural diversity and nonlinear optical properties.
AB  - Three new compounds (i.e., K2Sn2ZnSe6, Na2Ge2ZnSe6, and Na2In2GeSe6) with
      intriguing structural diversity and nonlinear optical properties were discovered
      for the first time. They crystallize in space groups P4/ncc, I4/mcm and Cc,
      respectively. In K2Sn2ZnSe6 and Na2Ge2ZnSe6, the [Sn(Ge)Se4] tetrahedra and
      [ZnSe4] tetrahedra are linked via edge-sharing to build up a 1D [Sn2ZnSe6]
      infinite chain separated by K(+)(Na(+)) cations along the c direction, while the
      structure of Na2In2GeSe6 is an interesting three-dimensional framework composed
      of [InSe4] and [GeSe4] tetrahedra via corner-sharing with Na(+) cations in the
      cavities. The experimental optical band gaps of these compounds were determined
      as 1.71(2) eV, 2.36(4) eV and 2.47(2) eV, respectively, according to UV-vis-NIR
      diffuse reflectance spectroscopy. Interestingly, in addition to the large band
      gap (1.80 eV for AgGaSe2, as a comparison), Na2In2GeSe6 exhibits phase-matchable
      nonlinear optical (NLO) properties with a powder second harmonic generation
      signal about 0.8 times that of AgGaS2. Moreover, Na2In2GeSe6 melts congruently at
      a rather low temperature of 671  degrees C, which suggests that bulk crystals can
      be easily obtained by the Bridgman-Stockbarger method. Our preliminary results
      indicate that Na2In2GeSe6 has promising applications in IR nonlinear optics.

PMID- 27049007
TI  - Immediate effect of valgus bracing on knee joint moments in meniscectomised
      patients: An exploratory study.
AB  - OBJECTIVES: Patients undergoing medial arthroscopic partial meniscectomy are at
      increased risk of developing and/or progressing knee osteoarthritis, with
      increased medial compartment load being a potential contributor. The aim of this
      study was to evaluate the immediate effect of a valgus unloader knee brace on
      knee joint moments in patients following medial arthroscopic partial
      meniscectomy. DESIGN: Within-participant design. METHODS: Twenty-two patients
      (age 35-55 years) who had undergone medial arthroscopic partial meniscectomy
      within the previous 8-15 months completed three-dimensional analysis of gait,
      forward lunge and one-leg rise during two conditions: with and without a valgus
      unloader knee brace. Outcome measures included the peak and impulse of the knee
      adduction moment and the peak knee flexion moment. RESULTS: The peak knee flexion
      moment increased during brace condition for forward lunge (mean difference [95%
      CI]) 0.54 [0.27-0.82] (Nm/(BW*HT)%), p<0.001 and one-leg rise (mean difference
      0.45 [95% CI 0.08-0.82] (Nm/(BW*HT)%), p=0.022). No other significant differences
      were found between conditions in any of the included tasks. CONCLUSIONS: A
      significant effect of the knee brace was detected in terms of an increase in peak
      knee flexion moment during the more demanding tasks such as forward lunge and one
      leg rise. This increase implies enhanced stability of the knee provided by the
      brace, which may induce increased knee function and knee-related confidence
      during strenuous tasks. Future research is required to explore the structural
      implications.

PMID- 27049008
TI  - Commentary on: SMAS Fusion Zones Determine the Subfascial and Subcutaneous
      Anatomy of the Human Face: Fascial Spaces, Fat Compartments, and Models of Facial
      Aging.

PMID- 27049009
TI  - Common Birthplace? Modern Plastic Surgery and Surrealism.

PMID- 27049010
TI  - Commentary on: Who is Publishing in Facial Cosmetic Surgery? A Citation Analysis
      Across Specialties Over Five Decades.

PMID- 27049011
TI  - Commentary on: Brachioplasty by Power-Assisted Liposuction and Fat Transfer: A
      Novel Approach That Obviates Skin Excision.

PMID- 27049012
TI  - Climate change and health in Bangladesh: a baseline cross-sectional survey.
AB  - BACKGROUND: Bangladesh is facing the unavoidable challenge of adaptation to
      climate change. However, very little is known in relation to climate change and
      health. This article provides information on potential climate change impact on
      health, magnitude of climate-sensitive diseases, and baseline scenarios of health
      systems to climate variability and change. DESIGN: A cross-sectional study using
      multistage cluster sampling framework was conducted in 2012 among 6,720
      households of 224 rural villages in seven vulnerable districts of Bangladesh.
      Information was obtained from head of the households using a pretested,
      interviewer-administered, structured questionnaire. A total of 6,720 individuals
      participated in the study with written, informed consent. RESULTS: The majority
      of the respondents were from the low-income vulnerable group (60% farmers or day
      labourers) with an average of 30 years' stay in their locality. Most of them
      (96%) had faced extreme weather events, 45% of people had become homeless and
      displaced for a mean duration of 38 days in the past 10 years. Almost all of the
      respondents (97.8%) believe that health care expenditure increased after the
      extreme weather events. Mean annual total health care expenditure was 6,555
      Bangladeshi Taka (BDT) (1 USD=77 BDT in 2015) and exclusively out of pocket of
      the respondents. Incidence of dengue was 1.29 (95% CI 0.65-2.56) and malaria
      13.86 (95% CI 6.00-32.01) per 1,000 adult population for 12 months preceding the
      data collection. Incidence of diarrhoea and pneumonia among under-five children
      of the households for the preceding month was 10.3% (95% CI 9.16-11.66) and 7.3%
      (95% CI 6.35-8.46), respectively. CONCLUSIONS: The findings of this survey
      indicate that climate change has a potential adverse impact on human health in
      Bangladesh. The magnitude of malaria, dengue, childhood diarrhoea, and pneumonia
      was high among the vulnerable communities. Community-based adaptation strategy
      for health could be beneficial to minimise climate change attributed health
      burden of Bangladesh.

PMID- 27049013
TI  - Current Threat of Triclabendazole Resistance in Fasciola hepatica.
AB  - Triclabendazole (TCBZ) is the only chemical that kills early immature and adult
      Fasciola hepatica (liver fluke) but widespread resistance to the drug greatly
      compromises fluke control in livestock and humans. The mode of action of TCBZ and
      mechanism(s) underlying parasite resistance to the drug are not known. Due to the
      high prevalence of TCBZ resistance (TCBZ-R), effective management of drug
      resistance is now critical for sustainable livestock production. Here, we discuss
      the current status of TCBZ-R in F. hepatica, the global distribution of
      resistance observed in livestock, the possible mechanism(s) of drug action, the
      proposed mechanisms and genetic basis of resistance, and the prospects for future
      control of liver fluke infections using an integrated parasite management (IPM)
      approach.

PMID- 27049014
TI  - Increased MRI-based cortical grey/white-matter contrast in sensory and motor
      regions in schizophrenia and bipolar disorder.
AB  - BACKGROUND: Schizophrenia and bipolar disorder share genetic risk factors and one
      possible illness mechanism is abnormal myelination. T1-weighted magnetic
      resonance imaging (MRI) tissue intensities are sensitive to myelin content.
      Therefore, the contrast between grey- and white-matter intensities may reflect
      myelination along the cortical surface. METHOD: MRI images were obtained from
      patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy
      controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast
      was computed at each vertex as the difference between average grey-matter
      intensity (sampled 0-60% into the cortical ribbon) and average white-matter
      intensity (sampled 0-1.5 mm into subcortical white matter), normalized by their
      average. Group differences were tested using linear models covarying for age and
      sex. RESULTS: Patients with schizophrenia had increased contrast compared to
      controls bilaterally in the post- and precentral gyri, the transverse temporal
      gyri and posterior insulae, and in parieto-occipital regions. In bipolar
      disorder, increased contrast was primarily localized in the left precentral
      gyrus. There were no significant differences between schizophrenia and bipolar
      disorder. Findings of increased contrast remained after adjusting for cortical
      area, thickness, and gyrification. We found no association with antipsychotic
      medication dose. CONCLUSIONS: Increased contrast was found in highly myelinated
      low-level sensory and motor regions in schizophrenia, and to a lesser extent in
      bipolar disorder. We propose that these findings indicate reduced intracortical
      myelin. In accordance with the corollary discharge hypothesis, this could cause
      disinhibition of sensory input, resulting in distorted perceptual processing
      leading to the characteristic positive symptoms of schizophrenia.

PMID- 27049020
TI  - Root trait diversity, molecular marker diversity, and trait-marker associations
      in a core collection of Lupinus angustifolius.
AB  - Narrow-leafed lupin (Lupinus angustifolius L.) is the predominant grain legume
      crop in southern Australia, contributing half of the total grain legume
      production of Australia. Its yield in Australia is hampered by a range of subsoil
      constraints. The adaptation of lupin genotypes to subsoil constraints may be
      improved by selecting for optimal root traits from new and exotic germplasm
      sources. We assessed root trait diversity and genetic diversity of a core
      collection of narrow-leafed lupin (111 accessions) using 191 Diversity Arrays
      Technology (DArT) markers. The genetic relationship among accessions was
      determined using the admixture model in STRUCTURE. Thirty-eight root-associated
      traits were characterized, with 21 having coefficient of variation values >0.5.
      Principal coordinate analysis and cluster analysis of the DArT markers revealed
      broad diversity among the accessions. An ad hoc statistics calculation resulted
      in 10 distinct populations with significant differences among and within them (P
      < 0.001). The mixed linear model test in TASSEL showed a significant association
      between all root traits and some DArT markers, with the numbers of markers
      associated with an individual trait ranging from 2 to 13. The percentage of
      phenotypic variation explained by any one marker ranged from 6.4 to 21.8%, with
      15 associations explaining >10% of phenotypic variation. The genetic variation
      values ranged from 0 to 7994, with 23 associations having values >240. Root
      traits such as deeper roots and lateral root proliferation at depth would be
      useful for this species for improved adaptation to drier soil conditions. This
      study offers opportunities for discovering useful root traits that can be used to
      increase the yield of Australian cultivars across variable environmental
      conditions.

PMID- 27049021
TI  - Stimulation of ipt overexpression as a tool to elucidate the role of cytokinins
      in high temperature responses of Arabidopsis thaliana.
AB  - Cytokinins (CKs) are phytohormones regulating plant growth and development as
      well as response to the environment. In order to evaluate their function in heat
      stress (HS) responses, the effect of CK elevation was determined during three
      types of HS - targeted to shoots, targeted to roots and applied to the whole
      plant. The early (30min) and longer term (3h) responses were followed at the
      hormonal, transcriptomic and proteomic levels in Arabidopsis transformants with
      dexamethasone-inducible expression of the CK biosynthetic gene
      isopentenyltransferase (ipt) and the corresponding wild-type (Col-0). Combination
      of hormonal and phenotypic analyses showed transient up-regulation of the
      CK/abscisic acid ratio, which controls stomatal aperture, to be more pronounced
      in the transformant. HS responses of the root proteome and Rubisco-immunodepleted
      leaf proteome were followed using 2-D gel electrophoresis and MALDI-TOF/TOF. More
      than 100 HS-responsive proteins were detected, most of them being modulated by CK
      increase. Proteome and transcriptome analyses demonstrated that CKs have longer
      term positive effects on the stress-related proteins and transcripts, as well as
      on the photosynthesis-related ones. Transient accumulation of CKs and stimulation
      of their signal transduction in tissue(s) not exposed to HS indicate that they
      are involved in plant stress responses.

PMID- 27049022
TI  - Urologic cancer in China.
AB  - Cancer remains to be the second most common cause of death, and its incidence and
      mortality rates are increasing in China. According to the 2015 National Central
      Cancer Registry (NCCR) of China, the incidence of bladder cancer and prostate
      cancer ranked sixth and seventh, respectively, in male cancers. The majority of
      prostate cancer patients were diagnosed at an advanced stage. Early diagnosis of
      prostate cancer is the key to improve prostate cancer survival in China. Radical
      prostatectomy or radical radiotherapy is the main treatment for localized
      prostate cancer, and a comprehensive therapy based on androgen deprivation
      therapy is the treatment for advanced disease. The most common histologic types
      of bladder cancer in China were urothelial carcinoma, followed by adenocarcinoma
      and squamous carcinoma. The majority of patients were diagnosed using white-light
      cystoscopy with biopsy. Fluorescence and narrow-band imaging cystoscopy had
      additional detection rates and are becoming more popular. Following Chinese
      guidelines, most non-muscle invasive bladder cancer patients were treated with
      diagnostic transurethral resection and more than half of the muscle invasive
      bladder cancer patients were treated with radical cystectomy. Due to the
      increased detection rate of kidney tumors by ultrasound in physical examination,
      the number of incidentally diagnosed renal cell carcinoma has increased.
      Localized kidney cancers are more and more often treated by nephron-sparing
      surgery. Radical nephrectomy is still the main treatment option for patients with
      locally advanced renal cell carcinoma. Both laparoscopic and robotic-assisted
      laparoscopic surgeries have been used in big medical centers. Both testicular
      cancer and penile cancer have lower incidence levels than that in Europe. As we
      have an enormous population base, the absolute patient number is big. The
      diagnosis and treatment follows the Chinese guidelines. In China, both medical
      professionals and public should concern more on the early diagnosis, as there is
      not enough cancer prevention information available. Urologists should also take a
      more active role in educating the population. 

PMID- 27049023
TI  - Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses
      after exposure to ionizing radiation.
AB  - Dendritic cell function is modulated by stromal cells, including fibroblasts.
      Although poorly understood, the signals delivered through this crosstalk
      substantially alter dendritic cell biology. This is well illustrated with release
      of TNF-alpha/IL-1beta from activated dendritic cells, promoting PGE2 secretion
      from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a
      key Th17-polarizing cytokine. We previously showed that ionizing radiation
      inhibited IL-23 production by human dendritic cells in vitro. In the present
      study, we investigated the hypothesis that dendritic cell-fibroblast crosstalk
      overcomes the suppressive effect of ionizing radiation to support appropriately
      polarized Th17 responses. Radiation (1-6 Gy) markedly suppressed IL-23 secretion
      by activated dendritic cells (P < 0.0001) without adversely impacting their
      viability and consequently, inhibited the generation of Th17 responses. Cytokine
      suppression by ionizing radiation was selective, as there was no effect on IL
      1beta, -6, -10, and -27 or TNF-alpha and only a modest (11%) decrease in IL-12p70
      secretion. Coculture with fibroblasts augmented IL-23 secretion by irradiated
      dendritic cells and increased Th17 responses. Importantly, in contrast to
      dendritic cells, irradiated fibroblasts maintained their capacity to respond to
      TNF-alpha/IL-1beta and produce PGE2, thus providing the key intermediary signals
      for successful dendritic cell-fibroblasts crosstalk. In summary, stromal
      fibroblasts support Th17-polarizing cytokine production by dendritic cells that
      would otherwise be suppressed in an irradiated microenvironment. This has
      potential ramifications for understanding the immune response to local
      radiotherapy. These findings underscore the need to account for the impact of
      microenvironmental factors, including stromal cells, in understanding the control
      of immunity.

PMID- 27049025
TI  - Phase transformation and deformation behavior of NiTi-Nb eutectic joined NiTi
      wires.
AB  - NiTi wires were brazed together via eutectic reaction between NiTi and Nb powder
      deposited at the wire contact region. Phase transformation and deformation
      behavior of the NiTi-Nb eutectic microstructure were investigated using
      transmission electron microscopy (TEM) and cyclic loading-unloading tests.
      Results show that R phase and B19' martensite transformation are induced by
      plastic deformation. R phase transformation, which significantly contributes to
      superelasticity, preferentially occurs at the interfaces between NiTi and
      eutectic region. Round-shaped Nb-rich phase with rod-like and lamellar-type
      eutectics are observed in eutectic regions. These phases appear to affect the
      deformation behavior of the brazed NiTi-Nb region via five distinct stages in
      stress-strain curves: (I) R phase reorientation, (II) R phase transformation from
      parent phase, (III) elastic deformation of reoriented martensite accompanied by
      the plastic deformation of Nb-rich phase and lamellar NiTi-Nb eutectic, (IV) B19'
      martensitic transformation, and (V) plastic deformation of the specimen. 

PMID- 27049024
TI  - Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH
      pathogenesis.
AB  - The accumulation of lipids is a histologic and biochemical hallmark of obesity
      associated nonalcoholic fatty liver disease (NAFLD). A subset of NALFD patients
      develops progressive liver disease, termed nonalcoholic steatohepatitis, which is
      characterized by hepatocellular apoptosis and innate immune system-mediated
      inflammation. These responses are orchestrated by signaling pathways that can be
      activated by lipids, directly or indirectly. In this review, we discuss palmitate
      and lysophosphatidylcholine (LPC)-induced upregulation of p53-upregulated
      modulator of apoptosis and cell-surface expression of the death receptor TNF
      related apoptosis-inducing ligand receptor 2. Next, we review the activation of
      stress-induced kinases, mixed lineage kinase 3, and c-Jun N-terminal kinase, and
      the activation of endoplasmic reticulum stress response and its downstream
      proapoptotic effector, CAAT/enhancer binding homologous protein, by palmitate and
      LPC. Moreover, the activation of these stress signaling pathways is linked to the
      release of proinflammatory, proangiogenic, and profibrotic extracellular vesicles
      by stressed hepatocytes. This review discusses the signaling pathways induced by
      lethal and sublethal lipid overload that contribute to the pathogenesis of NAFLD.

PMID- 27049026
TI  - Bed Bugs: Prevalence in Low-Income Communities, Resident's Reactions, and
      Implementation of a Low-Cost Inspection Protocol.
AB  - We examined bed bug prevalence in 2,372 low-income apartments within 43 buildings
      in four New Jersey cities using a combination of resident interviews, brief
      visual inspections, and monitoring with Climbup Insect Interceptors. Infestation
      rates ranged from 3.8 to 29.5% among the buildings, with an overall infestation
      rate of 12.3%. Within each apartment, the bed area trapped significantly more bed
      bugs per trap than the sofa (or upholstered chair) area. African American
      residents had a proportionally higher number of bed bug infestations than white
      residents. Women were more likely to report bed bug bite symptoms than men. Only
      68% of the residents who experienced bed bug infestations reported symptoms after
      being bitten (n = 475). Among those with self-reported symptoms (n = 319), the
      frequency of the reported symptoms was: pain 90%, itchiness 20%, welts 13%, and
      insomnia 8%. Fifty-nine percent of the residents (n = 539) who experienced bed
      bug infestations applied insecticides to control bed bugs. Climbup interceptors
      detected 89 +/- 1% and brief visual inspections detected 72 +/- 3% of the
      infestations. Only two out of 291 infestations were not detected by brief visual
      inspection or interceptors. Assuming US$50 per hour labor rate, the average per
      apartment cost for the building-wide bed bug monitoring protocol was US$12 per
      apartment. Forty-nine percent of the infestations detected by the protocol were
      in apartments whose residents were unaware of the bed bug activity.

PMID- 27049027
TI  - Toxicity of Sulfide and Ammonium to Aedes triseriatus Larvae (Diptera: Culicidae)
      in Water-Filled Tree Holes and Tires.
AB  - Ammonium and sulfide in water of tree hole and tire habitats of Aedes triseriatus
      Say larvae could accumulate to toxic levels, limiting growth and production of
      larvae and adults. Both ions were detected in water samples taken in longitudinal
      series over 11 dates from 10 habitats of each type during the larval growth
      season, at concentrations suggestive of reducing conditions in these habitats.
      Ammonium was more concentrated overall in water of both habitat types, while
      sulfide was more concentrated in tires than in tree holes. Water of tree holes
      was more acidic, whereas water in tires tended to be more basic, an important
      difference relative to the tendency of ammonium to form the more toxic ammonia
      moiety under basic conditions. Oxygen saturation was low in both habitat types,
      indicative of hypoxic conditions such that aerobic respiration would be limited.
      First-and fourth-instar larvae were sensitive to ammonium and sulfide in acute
      dose-response assays, but LC50 values were above maximum concentrations observed
      under field conditions, suggesting that toxic effects of ammonium and sulfide on
      larvae are not acute, but could be chronic.

PMID- 27049028
TI  - Ursane and tirucallane-type triterpenes of Boswellia rivae oleo-gum resin.
AB  - Two new ursane-type triterpenes characterized as 3-oxo-24-acetoxy-11alpha-hydroxy
      urs-12-ene (1) and methyl 3alpha-acetoxy-11alpha-methoxy-urs-12-en-24-oate (2),
      together with known compounds 3-11, were isolated from Boswellia rivae oleo-gum
      resin exudate. Their structural elucidation was accomplished using physical,
      chemical, and spectroscopic methods. The compounds exhibited weak to moderate
      antibacterial activities against some Gram-positive and Gram-negative bacteria. 

PMID- 27049029
TI  - Comparative lipidomic analysis of synovial fluid in human and canine
      osteoarthritis.
AB  - OBJECTIVE: The lipid profile of synovial fluid (SF) is related to the health
      status of joints. The early stages of human osteoarthritis (OA) are poorly
      understood, which larger animals are expected to be able to model closely. This
      study examined whether the canine groove model of OA represents early OA in
      humans based on the changes in the lipid species profile in SF. Furthermore, the
      SF lipidomes of humans and dogs were compared to determine how closely canine
      lipid species profiles reflect the human lipidome. METHODS: Lipids were extracted
      from cell- and cellular debris-free knee SF from nine donors with healthy joints,
      17 patients with early and 13 patients with late osteoarthritic changes, and nine
      dogs with knee OA and healthy contralateral joints. Lipid species were quantified
      by electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS:
      Compared with control canine SF most lipid species were elevated in canine OA SF.
      Moreover, the lipid species profiles in the canine OA model resembled early OA
      profiles in humans. The SF lipidomes between dog and human were generally
      similar, with differences in certain lipid species in the phosphatidylcholine
      (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) classes. CONCLUSIONS:
      Our lipidomic analysis demonstrates that SF in the canine OA model closely mimics
      the early osteoarthritic changes that occur in humans. Further, the canine SF
      lipidome often reflects normal human lipid metabolism.

PMID- 27049030
TI  - Early cathepsin K degradation of type II collagen in vitro and in vivo in
      articular cartilage.
AB  - OBJECTIVE: To characterize the initial events in the cleavage of type II collagen
      mediated by cathepsin K and demonstrate the presence of the resulting products in
      human and equine articular osteoarthritic cartilage. DESIGN: Equine type II
      collagen was digested with cathepsin K and the cleavage products characterized by
      mass spectrometry. Anti-neoepitope antibodies were raised against the most N
      terminal cleavage products and used to investigate the progress of collagen
      cleavage, in vitro, and the presence of cathepsin K-derived products in equine
      and human osteoarthritic cartilage. RESULTS: Six cathepsin K cleavage sites
      distributed throughout the triple helical region were identified in equine type
      II collagen. Most of the cleavages occurred following a hydroxyproline residue.
      The most N-terminal site was within three residues of the previously identified
      site in bovine type II collagen. Western blotting using anti-neoepitope
      antibodies showed that the initial cleavages occurred at the N-terminal sites and
      this was followed by more extensive degradation resulting in products too small
      to be resolved by SDS gel electrophoresis. Immunohistochemical staining of
      cartilage sections from equine or human osteoarthritic joints showed staining in
      lesional areas which was not observed in non-arthritic sites. CONCLUSIONS:
      Cathepsin K cleaves triple helical collagen by erosion from the N-terminus and
      with subsequent progressive cleavages. The liberated fragments can be detected in
      osteoarthritic cartilage and may represent useful biomarkers for disease
      activity.

PMID- 27049032
TI  - Monte Carlo simulation of body height in a spatial network.
AB  - BACKGROUND/OBJECTIVES: Recent evidence suggests clustering of human body height.
      We want to assess the consequences of connectedness in a spatial network on
      height clustering in an artificial society. SUBJECTS/METHODS: We used an agent
      based computer modelling technique (Monte Carlo simulation) and compared
      simulated height in a spatial network with characteristics of the observed
      geographic height distribution of three historic cohorts of Swiss military
      conscripts (conscripted in 1884-1891; 1908-1910; and 2004-2009). RESULTS:
      Conscript height shows several characteristic features: (1) height distributions
      are overdispersed. (2) Conscripts from districts with direct inter-district road
      connections tend to be similar in height. (3) Clusters of tall and clusters of
      short stature districts vary over time. Autocorrelations in height between late
      19th and early 21st century districts are low. (4) Mean district height depends
      on the number of connecting roads and on the number of conscripts per district.
      Using Monte Carlo simulation, we were able to generate these natural
      characteristics in an artificial society. Already 5% height information from
      directly connected districts is sufficient to simulate the characteristics of
      natural height distribution. Very similar observations in regular rectangular
      networks indicate that the characteristics of Swiss conscript height
      distributions do not so much result from the particular Swiss geography but
      rather appear to be general features of spatial networks. CONCLUSIONS: Spatial
      connectedness can affect height clustering in an artificial society, similar to
      that seen in natural cohorts of military conscripts, and strengthen the concept
      of connectedness being involved in the regulation of human height.

PMID- 27049031
TI  - Parenteral trace element provision: recent clinical research and practical
      conclusions.
AB  - The aim of this systematic review (PubMed, www.ncbi.nlm.nih.gov/pubmed and
      Cochrane, www.cochrane.org; last entry 31 December 2014) was to present data from
      recent clinical studies investigating parenteral trace element provision in adult
      patients and to draw conclusions for clinical practice. Important physiological
      functions in human metabolism are known for nine trace elements: selenium, zinc,
      copper, manganese, chromium, iron, molybdenum, iodine and fluoride. Lack of, or
      an insufficient supply of, these trace elements in nutrition therapy over a
      prolonged period is associated with trace element deprivation, which may lead to
      a deterioration of existing clinical symptoms and/or the development of
      characteristic malnutrition syndromes. Therefore, all parenteral nutrition
      prescriptions should include a daily dose of trace elements. To avoid trace
      element deprivation or imbalances, physiological doses are recommended.

PMID- 27049033
TI  - Prevalence and period trends of overweight and obesity in Australian young
      adults.
AB  - This analysis examines period trends in body weight of Australian 18-24 year
      olds. Secondary analysis of National Health Surveys was performed, including
      examination of socio-demographic determinants of obesity. The prevalence of
      overweight and obesity has increased from 24.0 and 5.1% in males and 13.2 and
      5.8% in females, respectively, in 1995 to 29.3 and 13.8% in males and 20.6 and
      20.6% in females in 2012. Mean body mass index (BMI) increased over time from
      23.7 (s.d. 3.5) for males and 22.4 (s.d. 4.0) for females in 1995 to 25.2 (s.d.
      4.8) and 25.5 (s.d. 5.9) in 2011/2. Lower educational attainment increased the
      odds of having BMI?25.00 kg/m(2) for both sexes (P=0.03 males and P<0.001
      females). Overweight and obesity were higher in rural females (P<0.05) and those
      socio-economically disadvantaged (P<0.0001). The obesity epidemic has worsened
      for Australian young adults and in particular young females.

PMID- 27049035
TI  - The potential double-burden of vitamin A malnutrition: under- and overconsumption
      of fortified table sugar in the Guatemalan highlands.
AB  - BACKGROUND/OBJECTIVES: In Guatemala, population-wide vitamin A fortification of
      table sugar has been operating for two decades. The objective of this study was
      to estimate the adequacy of vitamin A intakes in pregnant and lactating women
      from low-income, urban and rural communities. SUBJECTS/METHODS: One or two
      previous-day dietary recalls were collected in a convenience sample of 234
      pregnant and lactating women in the Western Highlands of Guatemala. Estimated
      daily intakes and main sources of total vitamin A, provitamin A and preformed
      vitamin A were calculated. Total intakes, adjusted for day-to-day variation, were
      examined in relation to estimated average requirements (EAR). RESULTS: Median
      estimated 1-day total vitamin A intake was 1177 MUg retinol activity equivalents
      (RAE) (interquartile range (IQR) 832-1782) in the urban site and 567 MUg RAE (IQR
      441-737) in the rural site. Women not meeting their status-specific vitamin A
      requirement were 3.5 times more common in the rural communities (31%) than in the
      urban confines (9%). In the urban area, 26 women (21%) had preformed vitamin A
      intakes above 1500 MUg on the day of data collection. Preformed vitamin A
      accounted for a median of 83.9% and 60.9% of the daily total vitamin A intake in
      the urban and rural sites, respectively. Sugar was the principal source of
      vitamin A, contributing 512 MUg RAE (IQR 343-749) in the urban site and 256 MUg
      RAE (IQR 189-363 MUg) in the rural area. CONCLUSIONS: The vitamin A contribution
      from fortified sugar can be a determinant of reaching adequacy; nevertheless, a
      significant proportion of pregnant and lactating women do not meet the EAR,
      especially in the rural setting.

PMID- 27049034
TI  - The 2015 Dutch food-based dietary guidelines.
AB  - The objective of this study was to derive food-based dietary guidelines for the
      Dutch population. The dietary guidelines are based on 29 systematic reviews of
      English language meta-analyses in PubMed summarizing randomized controlled trials
      and prospective cohort studies on nutrients, foods and food patterns and the risk
      of 10 major chronic diseases: coronary heart disease, stroke, heart failure,
      diabetes, breast cancer, colorectal cancer, lung cancer, chronic obstructive
      pulmonary disease, dementia and depression. The committee also selected three
      causal risk factors for cardiovascular diseases or diabetes: systolic blood
      pressure, low-density lipoprotein cholesterol and body weight. Findings were
      categorized as strong or weak evidence, inconsistent effects, too little evidence
      or effect unlikely for experimental and observational data separately. Next, the
      committee selected only findings with a strong level of evidence for deriving the
      guidelines. Convincing evidence was based on strong evidence from the
      experimental data either or not in combination with strong evidence from
      prospective cohort studies. Plausible evidence was based on strong evidence from
      prospective cohort studies only. A general guideline to eat a more plant food
      based dietary pattern and limit consumption of animal-based food and 15 specific
      guidelines have been formulated. There are 10 new guidelines on legumes, nuts,
      meat, dairy produce, cereal products, fats and oils, tea, coffee and sugar
      containing beverages. Three guidelines on vegetables, fruits, fish and alcoholic
      beverages have been sharpened, and the 2006 guideline on salt stayed the same. A
      separate guideline has been formulated on nutrient supplements. Completely food
      based dietary guidelines can be derived in a systematic and transparent way.

PMID- 27049036
TI  - The effect of vitamin D on thyroid autoimmunity in non-lactating women with
      postpartum thyroiditis.

PMID- 27049037
TI  - Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target
      in Insulinomas.
AB  - The long-term prognosis after surgical resection of malignant insulinoma (INS) is
      poor. Novel adjuvant therapies, specifically targeting cancer stem cells (CSCs),
      are warranted. Therefore, the goal of this study was to characterize and target
      putative INS CSCs. Using fluorescence-activated cell sorting, human INS cell line
      CM and pancreatic carcinoid cell line BON1 were screened for the presence of stem
      cell-associated markers. CD90, CD166, and GD2 were identified as potential CSC
      markers. Only CD90(+) INS cells had an increased tumor-initiating potential in
      athymic nude mice. Anti-CD90 monoclonal antibodies decreased the viability and
      metastatic potential of injected cells in a zebrafish embryo INS xenograft model.
      Primary INS stained positive for CD90 by immunohistochemistry, however also
      intratumoral fibroblasts and vascular endothelium showed positive staining. The
      results of this study suggest that anti-CD90 monoclonals form a potential novel
      adjuvant therapeutic modality by targeting either INS cells directly, or by
      targeting the INS microenvironment.

PMID- 27049038
TI  - Emerging In Vitro Liver Technologies for Drug Metabolism and Inter-Organ
      Interactions.
AB  - In vitro liver models provide essential information for evaluating drug
      metabolism, metabolite formation, and hepatotoxicity. Interfacing liver models
      with other organ models could provide insights into the desirable as well as
      unintended systemic side effects of therapeutic agents and their metabolites.
      Such information is invaluable for drug screening processes particularly in the
      context of secondary organ toxicity. While interfacing of liver models with other
      organ models has been achieved, platforms that effectively provide human-relevant
      precise information are needed. In this concise review, we discuss the current
      state-of-the-art of liver-based multiorgan cell culture platforms primarily from
      a drug and metabolite perspective, and highlight the importance of media-to-cell
      ratio in interfacing liver models with other organ models. In addition, we
      briefly discuss issues related to development of optimal liver models that
      include recent advances in hepatic cell lines, stem cells, and challenges
      associated with primary hepatocyte-based liver models. Liver-based multiorgan
      models that achieve physiologically relevant coupling of different organ models
      can have a broad impact in evaluating drug efficacy and toxicity, as well as
      mechanistic investigation of human-relevant disease conditions.

PMID- 27049039
TI  - Drugs as Possible Triggers of Takotsubo Cardiomyopathy: A Comprehensive
      Literature Search - Update 2015.
AB  - BACKGROUND: In 2011 a list of 20 drugs linked to drug-induced Tako-Tsubo
      cardiomyopathy (TCM) was published. Thus, the objectives were both to identify
      cases of drug-induced TCM, and update the 2011 list of drugs as possible triggers
      of this cardiomyopathy. METHOD: As the 2011 report of drug-induced TCM, case
      reports of drug-induced TCM were identified by a comprehensive search in
      Medline/PubMed database. From December 2010 to March 2015 search terms were
      Takotsubo cardiomyopathy, Takotsubo cardiomyopathy, stress cardiomyopathy,
      transient-left-ventricular ballooning syndrome, ampulla cardiomyopathy, apical
      ballooning syndrome, OR broken heart syndrome; together with "iatrogenic", "drug
      induced", OR "induced by". Publications limited to English, Spanish, and French,
      in humans, and with full texts were retrieved. Articles that recognized any drug
      as a possible trigger of TCM were selected. RESULTS: Overall, 405 different
      references were retrieved and 67 were selected (62 case reports and 5 case
      series) involving 78 patient cases with TCM possibly associated to drugs were
      reviewed. At total of 44 drugs were recognized as possible drug-induced TCM,
      mainly with sympathetic effect, and 37 (84.1%) were different to those 20
      identified in the 2011 review; therefore, a list of 57 drugs associated to TCM
      was obtained. CONCLUSION: There are new case reports that linked drug-use with
      the development of TCM. The list of 57 drugs obtained is principally integrated
      by drugs that generate sympathetic overstimulation. Consequently, the
      recommendation "drug-induced TCM would be considered in patients with TCM,
      particularly those in which no clear emotional or stress trigger could be
      identified" is endorsed.

PMID- 27049040
TI  - [Osteoporosis: How, when and how far].

PMID- 27049041
TI  - [2006-2016: Ten years of immersion in the world of rare diseases].

PMID- 27049042
TI  - Bone loss in chronic kidney disease: Quantity or quality?
AB  - Chronic kidney disease (CKD) patients experience bone loss and fracture because
      of a specific CKD-related systemic disorder known as CKD-mineral bone disorder
      (CKD-MBD). The bone turnover, mineralization, and volume (TMV) system describes
      the morphological bone lesions in renal osteodystrophy related to CKD-MBD. Bone
      turnover and bone volume are defined as high, normal, or low, and bone
      mineralization is classified as normal or abnormal. All types of bone histology
      related to TMV are responsible for both bone quantity and bone quality losses in
      CKD patients. This review focuses on current bone quantity and bone quality
      losses in CKD patients and finally discusses potential therapeutic measures.

PMID- 27049043
TI  - CT-abnormalities, bacteriology and symptoms of sinonasal disease in children with
      Cystic Fibrosis.
AB  - BACKGROUND: Sinonasal pathology in adults with Cystic Fibrosis (CF) is common but
      the extent of CT-abnormalities and symptoms of sinonasal disease in children with
      CF and the age of onset are less frequently studied. METHODS: In this
      observational, cross-sectional study 58 children with CF from two CF centres were
      included. All subjects completed a questionnaire regarding sinonasal symptoms,
      underwent a CT scan of the paranasal sinuses, and in each subject a culture of
      the upper airways was performed. Subjects were divided in 6 age cohorts (0-2, 3
      5, 6-8, 9-11, 12-14 and 15-17years) and were divided into severe and mild CF
      based on their CFTR mutation. Opacification of the sinonasal system of the
      subjects was compared with opacification on MRI-scans of an age-matched control
      group without CF. RESULTS: Most frequently reported symptoms were nasal
      obstruction and posterior/anterior nasal discharge. Opacification was abundant in
      every age cohort of the study group and was significantly more compared to the
      control group. In patients with severe CF the opacification was higher than
      subjects with mild CF. Upper airway cultures showed predominantly Staphylococcus
      aureus, Haemophilus influenzae and Pseudomonas aeruginosa. CONCLUSION: CT
      abnormalities indicating sinonasal disease and symptoms are present from shortly
      after birth which may argue for a thorough examination of the upper airways in
      children with CF.

PMID- 27049044
TI  - Single Molecule Simulation of Diffusion and Enzyme Kinetics.
AB  - This work presents a molecular-scale agent-based model for the simulation of
      enzymatic reactions at experimentally measured concentrations. The model
      incorporates stochasticity and spatial dependence, using diffusing and reacting
      particles with physical dimensions. We developed strategies to adjust and
      validate the enzymatic rates and diffusion coefficients to the information
      required by the computational agents, i.e., collision efficiency, interaction
      logic between agents, the time scale associated with interactions (e.g.,
      kinetics), and agent velocity. Also, we tested the impact of molecular location
      (a source of biological noise) in the speed at which the reactions take place.
      Simulations were conducted for experimental data on the 2-hydroxymuconate
      tautomerase (EC 5.3.2.6, UniProt ID Q01468) and the Steroid Delta-isomerase (EC
      5.3.3.1, UniProt ID P07445). Obtained results demonstrate that our approach is in
      accordance to existing experimental data and long-term biophysical and
      biochemical assumptions.

PMID- 27049045
TI  - Interstitial fluid flow of alveolar primary septa after pneumonectomy.
AB  - Neoalveolation is known to occur in the remaining lung after pneumonectomy. While
      compensatory lung growth is a complex process, stretching of the lung tissue
      appears to be crucial for tissue remodeling. Even a minute shear stress exerted
      on fibroblasts in the interstitial space is known to trigger cell differentiation
      into myofibroblast that are essential to building new tissues. We hypothesize
      that the non-uniform motion of the primary septa due to their heterogeneous
      mechanical properties under tidal breathing induces a spatially unique
      interstitial flow and shear stress distribution in the interstitial space. This
      may in turn trigger pulmonary fibroblast differentiation and neoalveolation. In
      this study, we developed a theoretical basis for how cyclic motion of the primary
      septal walls with heterogeneous mechanical properties affects the interstitial
      flow and shear stress distribution. The velocity field of the interstitial flow
      was expressed by a Fourier (complex) series and its leading term was considered
      to induce the basic structure of stress distribution as long as the dominant
      length scale of heterogeneity is the size of collapsed alveoli. We conclude that
      the alteration of mechanical properties of the primary septa caused by
      pneumonectomy can develop a new interstitial flow field, which alters the shear
      stress distribution. This may trigger the differentiation of resident
      fibroblasts, which may in turn induce spatially unique neoalveolation in the
      remaining lung. Our example illustrates that the initial forming of new alveoli
      about half the size of the original ones.

PMID- 27049046
TI  - Assessing and comparison of different machine learning methods in parent
      offspring trios for genotype imputation.
AB  - Genotype imputation is an important tool for prediction of unknown genotypes for
      both unrelated individuals and parent-offspring trios. Several imputation methods
      are available and can either employ universal machine learning methods, or deploy
      algorithms dedicated to infer missing genotypes. In this research the performance
      of eight machine learning methods: Support Vector Machine, K-Nearest Neighbors,
      Extreme Learning Machine, Radial Basis Function, Random Forest, AdaBoost,
      LogitBoost, and TotalBoost compared in terms of the imputation accuracy,
      computation time and the factors affecting imputation accuracy. The methods
      employed using real and simulated datasets to impute the un-typed SNPs in parent
      offspring trios. The tested methods show that imputation of parent-offspring
      trios can be accurate. The Random Forest and Support Vector Machine were more
      accurate than the other machine learning methods. The TotalBoost performed
      slightly worse than the other methods.The running times were different between
      methods. The ELM was always most fast algorithm. In case of increasing the sample
      size, the RBF requires long imputation time.The tested methods in this research
      can be an alternative for imputation of un-typed SNPs in low missing rate of
      data. However, it is recommended that other machine learning methods to be used
      for imputation.

PMID- 27049047
TI  - Epidemiological, evolutionary, and economic determinants of eradication tails.
AB  - Despite modern medical interventions, infectious diseases continue to generate
      huge socio-economic losses. The benefits of eradicating a disease are therefore
      high. While successful with smallpox and rinderpest, many other eradication
      attempts have failed. Eradications require huge and costly efforts, which can be
      sustained only if sufficient progress can be achieved. While initial successes
      are usually obtained more easily, progress often becomes harder as a disease
      becomes rare in the eradication endgame. A long eradication tail of slowly
      decreasing incidence levels can frustrate eradication efforts, as it becomes
      unclear whether progress toward eradication is still being made and how much more
      needs to be invested to push the targeted disease beyond its extinction
      threshold. Realistic disease dynamics are complicated by evolutionary responses
      to interventions and by interactions among different temporal and spatial scales.
      Models accounting for these complexities are required for understanding the
      shapes of eradication tails. In particular, such models allow predicting how hard
      or costly eradication will be, and may even inform in which manner progress has
      to be assessed during the eradication endgame. Here we outline a general
      procedure by analyzing the eradication tails of generic SIS diseases, taking into
      account two major ingredients of realistic complexity: a group-structured host
      population in which host contacts within groups are more likely than host
      contacts between groups, and virulence evolution subject to a trade-off between
      host infectivity within groups and host mobility among groups. Disentangling the
      epidemiological, evolutionary, and economic determinants of eradication tails, we
      show how tails of different shapes arise depending on salient model parameters
      and on how the extinction threshold is approached. We find that disease evolution
      generally extends the eradication tail and show how the cost structure of
      eradication measures plays a key role in shaping eradication tails.

PMID- 27049048
TI  - Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted
      approach toward peptide-based immunotherapy.

PMID- 27049049
TI  - Rifapentine-loaded PLGA microparticles for tuberculosis inhaled therapy:
      Preparation and in vitro aerosol characterization.
AB  - Inhaled delivery of drugs incorporated into poly (lactic-co-glycolic acid) (PLGA)
      microparticles allows a sustained lung concentration and encourages phagocytosis
      by alveolar macrophages that harboring Mycobacterium tuberculosis. However,
      limited data are available on the effects of physicochemical properties of PLGA,
      including the monomer ratio (lactide:glycide) and molecular weight (MW) on the
      aerosol performance, macrophage uptake, and toxicity profile. The present study
      aims to address this knowledge gap, using PLGAs with monomer ratios of 50:50,
      75:25 and 85:15, MW ranged 24 - 240kDa and an anti-tuberculosis (TB) drug,
      rifapentine. The PLGA-rifapentine powders were produced through a solution spray
      drying technique. The particles were spherical with a smooth surface and a volume
      median diameter around 2MUm (span ~2). When the powders were dispersed using an
      Osmohaler((r)) at 100L/min for 2.4s, the fine particle fraction (FPFtotal, wt.%
      particles in aerosol <5MUm relative to the total recovered drug mass) was ranged
      between 52 and 57%, with no significant difference between the formulations. This
      result suggests that the monomer ratio and MW are not crucial parameters for the
      aerosol performance of PLGA. The phagocytosis analysis was performed using Thp-1
      monocyte-derived macrophages. The highest rate of uptake was observed in PLGA
      85:15 followed by 75:25 and 50:50 with about 90%, 80% and 70%, respectively
      phagocytosis over 4h of exposure. Furthermore, the cytotoxicity analysis on Thp-1
      and human lung adenocarcinoma epithelial cells demonstrated that PLGA
      concentration up to 1.5mg/mL, regardless of the monomer composition and MW, were
      non-toxic. In conclusion, the monomer ratio and MW are not crucial in determining
      the aerosol performance and cytotoxicity profile of PLGA however, the particles
      with high lactide composition have a superior tendency for macrophage uptake. 

PMID- 27049050
TI  - Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous
      solid dispersions using combination of polymeric blends: A QbD approach.
AB  - Efavirenz is a non-nucleoside reverse transcriptase inhibitor and categorized in
      to BCS class II drug. The aim of the present investigation was to apply quality
      by design approach to enhance the solubility, dissolution and stability of
      amorphous solid dispersions (ASDs) of efavirenz using a combination of
      Soluplus(r) and HPMCAS-HF polymers. In design of experiments, the user defined
      quadratic model was used to study the effect of variable concentrations of
      Soluplus(r) and HPMCAS-HF for the formation of ASDs of efavirenz. Similarly, a
      prototype ASD was made using Soluplus(r) as a carrier with efavirenz loading of
      30%. The efavirenz ASDs granular extrudates were evaluated for saturation
      solubility as well as dissolution rate studies. X-ray powder diffraction,
      Differential scanning calorimetry, Fourier transform infrared, Atomic force
      microscopy and FTIR imaging to determine the solid state of efavirenz in the
      ASDs. DSC and XRD data confirmed that bulk crystalline efavirenz transformed to
      the amorphous form during the hot melt extrusion processing. Prototype ASD batch
      showed instability upon storage as per ICH guidelines over a period of 6months,
      observations inferred from DSC, XRD and in vitro dissolution studies. The maximum
      dissolution rate was observed when Soluplus(r) and HPMCAS-HF was in ratio of
      (60:20) as optimized by design of experiments study. Moreover, the optimized ASDs
      batch were stable at 40 degrees C, 75% RH for a period of 6months without any
      dissolution rate changes, and remained into amorphous state. 

PMID- 27049051
TI  - CRISPR/Cas9 produces anti-hepatitis B virus effect in hepatoma cells and
      transgenic mouse.
AB  - Chronic infection of hepatitis B virus (HBV) is at risk of liver cirrhosis and
      hepatocellular carcinoma and remains one of the major public health problems
      worldwide. It is a major barrier of persistence HBV cccDNA under current
      antiviral therapy as novel strategies of disrupting HBV cccDNA is pressing. The
      (CRISPR)/Cas9 system is presently emerging in gene editing and we also apply it
      for targeting and deleting the conserved regions of HBV genome. Two homologous
      sequences of HBV S and X genes were carried with CRISPR/Cas9 endonuclease to
      build pCas9 constructs, which may mediate anti-HBV effects of in vitro and in
      vivo systems in this study. The results showed the better anti-HBV productions by
      pCas9-2 and without significant differences in between Huh7 and HepG2 cells.
      CRISPR/Cas9 direct cleavage and mutagenesis were further analyzed of in vitro
      system. In the M-TgHBV mouse model of HBV, injection of pCas9 constructs by
      hydrodynamics decreased HBsAg of sera and liver HBcAg. In conclusion, this
      designed CRISPR/Cas9 system can induce anti-HBV effects and potentially consider
      as a novel therapeutic agent against chronic HBV infection.

PMID- 27049053
TI  - Bioequivalence and food effect study of enteric-coated mesalazine tablets in
      healthy Chinese volunteers by HPLC-ESI-MS/MS.
AB  - OBJECTIVE: To establish a developed HPLC-ESI-MS/MS method for simultaneous
      determination of mesalazine (5-ASA) and its major metabolite N-Ac-5-ASA in human
      plasma and to investigate bioequivalence of two enteric-coated mesalazine tablets
      as well as the effect of high-fat food on the pharmacokinetics of 5-ASA and N-Ac
      5-ASA. METHODS: In this open-label, randomized, crossover, two-states, four
      period study, 20 healthy Chinese volunteers were randomized to receive a single
      oral dose of trial or reference preparation (2 * 250 mg) under fasting and fed
      state. Plasma samples were obtained at 0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8,
      10, 12, 24, and 36 hours postdose and were measured by a developed HPLC-ESI-MS/MS
      method. Safety and tolerability were assessed throughout the study. RESULTS: The
      HPLC-ESI-MS/MS method required only 7.0 minutes run time and was successfully
      applied in analyzing ~ 2,000 samples. High-fat-food administration prolonged tmax
      of 5-ASA and N-Ac-5-ASA (p < 0.05), while AUC was not significantly affected by
      the meal (p > 0.05). The 90% confidence intervals (CIs) of the fed/fasting and
      trial/reference ratios of log-transformed Cmax and AUC were within 80-125%. The
      two one-sided t-tests showed that the trial and reference preparation were
      bioequivalent (p > 0.05). CONCLUSIONS: This developed HPLC-ESI-MS/MS method is
      suitable for massive biomedical analysis. Trial and reference preparations are
      bioequivalent under fasting and fed state. High-fat-food administration delays
      the absorption of mesalazine while total exposure is not affected. Dietary habits
      should always be taken into consideration when enteric-coated mesalazine tablets
      were prescribed to patients.

PMID- 27049054
TI  - Prevalence of overweight in schizophrenia patients in Asia: findings of the
      research on Asian psychotropic prescription patterns (REAP) study.
AB  - OBJECTIVE: This study examined the proportion of overweight in schizophrenia
      inpatients in selected Asian countries and territories and its independent
      demographic and clinical correlates. METHOD: Data on 1,534 hospitalized
      schizophrenia patients in 9 Asian countries and territories were collected by a
      review of medical files supplemented by a clinical interview during a 1-month
      period. Patients' sociodemographic and clinical characteristics, prescriptions of
      psychotropic drugs, and Body Mass Index (BMI) were recorded using a standardized
      protocol and data collection procedure. For analyzes, BMI >= 25 kg/m2 was defined
      as overweight. RESULTS: The proportion of overweight was 35.8% (549/1,534) in the
      entire sample, with 39.7% (224/564) in females and 33.5% (325/970) in males (p =
      0.01) and with wide inter-country variations. Multiple logistic regression
      analysis revealed that after controlling for study sites, overweight was
      independently associated with more frequent use of mood stabilizers (p < 0.001,
      odds ration (OR) = 1.4, 95% confidence interval (CI) = 1.1-1.8) and longer length
      of illness (p < 0.001, OR = 1.6, 95% CI = 1.2-2.1) but was less likely found in
      male patients (p = 0.003, OR = 0.7, 95% CI = 0.5-0.8). CONCLUSIONS: The
      prevalence of overweight Asian schizophrenia patients is significantly lower than
      the reported figures among their Western counterparts. There is considerable
      variation in prevalence of overweight schizophrenia patients within Asian
      countries and territories.

PMID- 27049052
TI  - A picture is worth a thousand words: maps of HIV indicators to inform research,
      programs, and policy from NA-ACCORD and CCASAnet clinical cohorts.
AB  - INTRODUCTION: Maps are powerful tools for visualization of differences in health
      indicators by geographical region, but multi-country maps of HIV indicators do
      not exist, perhaps due to lack of consistent data across countries. Our objective
      was to create maps of four HIV indicators in North, Central, and South American
      countries. METHODS: Using data from the North American AIDS Cohort Collaboration
      on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America
      network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for
      HIV clinical care, proportion retained in HIV primary care, proportion prescribed
      antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral
      load (VL) from 2010 to 2012 for North, Central, and South America. The 15
      Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil,
      Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2-7% of
      persons known to be living with HIV in these countries. RESULTS: Study
      populations were selected for each indicator: median CD4 at presentation for care
      was estimated among 14,811 adults; retention was estimated among 87,979 adults;
      ART use was estimated among 84,757 adults; and suppressed VL was estimated among
      51,118 adults. Only three US states and the District of Columbia had a median CD4
      at presentation >350 cells/mm(3). Haiti, Mexico, and several states had >85%
      retention in care; lower (50-74%) retention in care was observed in the US West,
      South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest
      (90%) in Mexico. The percentages of patients with suppressed VL in the US South
      and Northeast were lower than in most of Central and South America. CONCLUSIONS:
      These maps provide visualization of gaps in the quality of HIV care and allow for
      comparison between and within countries as well as monitoring policy and
      programme goals within geographical boundaries.

PMID- 27049055
TI  - Comparative bioavailability of two tablet formulations of emtricitabine/tenofovir
      in healthy, fasting volunteers: a single-dose, randomized-sequence, open-label
      crossover study.
AB  - OBJECTIVE: To evaluate the relative bioavailability of a new formulation of
      emtricitabine (EMT) 200 mg and tenofovir disoproxil fumarate (TNF) 300 mg and to
      compare with reference formulation to meet regulatory criteria in Argentina.
      METHODS: A randomized-sequence, open-label, twoperiod crossover study was
      conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral
      dose of T or R formulations was followed by a 7-day washout period. Samples were
      collected at baseline, 0.25, 0.50, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 7, 12, 24,
      and 48 hours after administration. EMT and TNF were determined by LC-MS/MS.
      RESULTS: Geometric means (90% CI) Cmax for EMT in test and reference were
      1,891.22 (1,777.1 - 2,187.31) and 1,830.31 (1,721.19 - 2,134.01) ng/mL, the AUC0
      t were 10,283.07 (9,624.29 - 11,566.34) and 10,518.76 (9,942.79 - 11,578.30) ng *
      h/mL and the AUC0-infinity were 10,615.14 (9,948.56 - 11,866.26) and 10,804.12
      (10,221.04 - 11,864.85) ng * h/mL, respectively. For TNF test and reference, Cmax
      geometric means (CI range) were 202.91 (187.91 - 255.78) and 212.04 (195.98 -
      264.87) ng/mL, AUC0-t were 1,429.96 (1,334.63 - 1,680.00) and 1,420.75 (1,326.76 
      1,622.18) ng * h/mL and AUC0-infinity were 1,657.11 (1,551.60 - 1,921.75) and
      1,631.84 (1,523.95 - 1,857.97), respectively. No differences were detected
      between the formulations. The test/reference ratios (90% CI) for Cmax, AUC0-t,
      and AUC0-infinity were 103.33% (95.7 - 111.6), 97.76% (93.6 - 102.1), and 98.25%
      (94.3 - 102.4) for EMT, and 95.70% (85.9 - 106.6), 95.20% (83.4 - 108.6) and
      91.10% (80.7 - 102.7) for TNF. CONCLUSIONS: In this single-dose study, the
      EMT/TNF tablets (test formulation) met the standard 90% CI criterion for
      bioequivalence with the reference formulation.

PMID- 27049056
TI  - Pharmacokinetic properties and bioequivalence of spironolactone tablets in
      fasting and fed healthy Chinese male subjects.
AB  - BACKGROUND AND PURPOSE: Spironolactone is a potassium-sparing diuretic and is a
      competitive antagonist of aldosterone, which is widely used in the treatment of
      primary aldosteronism, essential hypertension, congestive cardiac failure, and
      various edematous states. The purpose of this study was to compare the
      pharmacokinetic properties and bioequivalence of the two formulations of
      spironolactone tablets in healthy Chinese male subjects under fasting and fed
      condition. METHODS: A total of 40 male subjects were enrolled in this randomized,
      open-label, two-period crossover study, subjects in 2 groups (20 individuals in
      each group) received a single 100-mg dose of test or reference spironolactone
      tablet formulations with a 2-week washout period under both fasting and fed
      condition. The plasma concentrations of canrenone, a major active metabolite of
      spironolactone, were quantified by a validated high performance liquid
      chromatography-tandem mass spectrometry method. The pharmacokinetic parameters
      including AUC0-tlast, AUC0-infinity, tmax, and Cmax were employed to test
      bioequivalence. RESULTS: The relative bioavailability was 99.2 +/- 11.6% and 97.6
      +/- 7.4% under fasting and fed condition, respectively. The 90% confidence
      intervals of the adjusted geometric mean ratio (test/reference) of Cmax, AUC0
      tlast, and AUC0-infinity were 89.7-113.8%, 93.9-103.3%, and 90.0-103.0% in
      fasting study and 87.7-102.3%, 95.1-99.5%, and 94.1-98.9% in fed study,
      respectively. CONCLUSIONS: Based on pharmacokinetic parameters and the Chinese
      Food and Drug Administration's guidance and regulatory criteria for
      bioequivalence, the test and reference formulations of spironolactone were
      bioequivalent under both fasting and fed condition. Both formulations were
      generally well tolerated, with no adverse reaction reported.

PMID- 27049057
TI  - Population pharmacokinetics of IND/GLY (indacaterol/glycopyrronium) in COPD
      patients.
AB  - OBJECTIVE: Indacaterol/glycopyrronium (IND/GLY) is a fixed-dose combination (FDC)
      of indacaterol, an inhaled long-acting beta2-agonist (LABA), and glycopyrronium,
      an inhaled long-acting muscarinic antagonist (LAMA), developed as a maintenance
      bronchodilator treatment for patients with chronic obstructive pulmonary disease
      (COPD). A population pharmacokinetic (PK) analysis was performed to describe the
      PK profiles of indacaterol and glycopyrronium following the twice daily (b.i.d.)
      and once daily (o.d.) inhalation regimens as FDC or as monotherapies and to
      determine the effect of covariates. METHODS: PK data in 556 COPD patients were
      pooled from three phase 3 studies. Two phase 3 studies investigated IND/GLY
      27.5/12.5 MUg b.i.d. and the third study investigated IND/GLY 110/50 MUg o.d.
      Body weight was included in the model with fixed allometric coefficients for
      indacaterol and glycopyrronium. RESULTS: Statistically significant effects of
      smoking, age, and sex on apparent clearance of indacaterol; smoking, and
      estimated glomerular filtration rate at baseline on apparent clearance and
      Japanese ethnicity on apparent central volume of distribution of glycopyrronium
      were identified. CONCLUSION: Systemic exposure to indacaterol and glycopyrronium
      was shown to be dose-proportional and time-independent following inhalation
      either as monotherapies or FDC. None of the identified covariate effects was
      judged to be clinically relevant. There is no PK drug-drug interaction between
      indacaterol and glycopyrronium in its FDC.

PMID- 27049058
TI  - Vaccine-induced Th17 cells are established as resident memory cells in the lung
      and promote local IgA responses.
AB  - The ability to mount accelerated and efficient mucosal immune responses is
      critically important to prevent the establishment of many infections. Secretion
      of immunoglobulin A (IgA) is a key component in this first line of defense, but
      the underlying cellular mechanisms are still not completely understood. We have
      evaluated different routes of immunization and examined the requirements for IgA
      induction in the airway mucosa. We demonstrate that subcutaneous priming with a
      recombinant antigen in a T helper (Th)17-inducing adjuvant followed by airway
      boosting promotes high and sustained levels of IgA in the lungs. This response is
      associated with germinal center formation in the lung-draining lymph nodes. The
      lung IgA response is dependent on Th17 cells and absent if interleukin (IL)-17 is
      depleted or when priming with vaccines inducing only Th1 or Th2 responses. We
      used intravascular staining to demonstrate that IgA+ B cells and chemokine
      receptor 6 (CCR6)+Th17 cells are recruited to the lung parenchyma after the
      airway booster immunization. Once recruited to the lung parenchyma, the Th17
      cells transform into resident lymphocytes that persist in the lung tissue for at
      least 10 weeks. Here, they facilitate the accelerated recruitment of T and B
      cells resulting in an accelerated IgA recall response to a second airway booster
      immunization.

PMID- 27049059
TI  - Macrophage migration inhibitory factor deficiency enhances immune response to
      Nippostrongylus brasiliensis.
AB  - Infections with helminth parasites are endemic in the developing world and are a
      target for intervention with new therapies. Macrophage migration inhibitory
      factor (MIF) is a cytokine with pleiotropic effects in inflammation and immune
      responses. We investigated the role of MIF in a naturally cleared model of
      helminth infection in rodents, Nippostrongylus brasiliensis. At day 7
      postinfection, MIF-deficient (MIF-/-) mice had reduced parasite burden and
      mounted an enhanced type 2 immune response (Th2), including increased Gata3
      expression and interleukin-13 (IL-13) production in the mesenteric lymph nodes
      (MLNs). Bone marrow reconstitution demonstrated that MIF produced from
      hematopoietic cells was crucial and Rag1-/- reconstitution provided direct
      evidence that MIF-/- CD4+ T cells were responsible for the augmented parasite
      clearance. MIF-/- CD4+ T cells produced less IL-6 postinfection, which correlated
      with enhanced Th2 responses. MIF-/- CD4+ T cells exhibited lower nuclear factor
      kappaB activation, potentially explaining the reduction in IL-6. Finally, we
      demonstrated enhanced clearance of the parasite and Th2 response in wild-type
      mice treated with the MIF tautomerase inhibitor, sulforaphane, a compound found
      naturally found in cruciferous vegetables. These results are the first to
      describe the importance of the tautomerase enzyme activity in MIF function in N.
      brasiliensis infection.

PMID- 27049060
TI  - Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic
      cells, and endothelium and modulated during inflammatory bowel disease.
AB  - The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates
      ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the
      cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation
      of S1P1 expression in lymphocytes after administration of dextran sulfate sodium
      (DSS), after colitis induced by transfer of CD4+CD45RBhi cells, and by crossing a
      mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression
      of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on
      lymphocyte behavior and S1P1 expression. We found that not only T and B cells
      express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic
      but not acute inflammatory signals increased S1P1 expression, while the enzymes
      that control tissue S1P levels in mice and humans with inflammatory bowel disease
      (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally,
      we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and
      retention of Naive but not effector T cells. Our data demonstrate that chronic
      inflammation modulates S1P1 expression and tissue S1P levels and suggests that
      the anti-inflammatory properties of S1PR agonists might not be solely due to
      their lymphopenic effects, but also due to potential effects on DC migration and
      vascular barrier function.

PMID- 27049061
TI  - Bacteroides are associated with GALT iNKT cell function and reduction of
      microbial translocation in HIV-1 infection.
AB  - Invariant natural killer T (iNKT) cells are innate-like T cells that respond to
      lipid antigens presented by CD1d. These immunoregulatory cells have the capacity
      for rapid cytokine release after antigen recognition and are essential for the
      activation of multiple arms of the immune response. HIV-1 infection is associated
      with iNKT cell depletion in the peripheral blood; however, their role in the
      gastrointestinal-associated lymphoid tissue (GALT) is less well studied. Our
      results show that iNKT cells are found at a higher frequency in GALT compared
      with blood, particularly in HIV-1 elite controllers. The capacity of iNKT cells
      to produce interleukin-4 (IL-4) and IL-10 in the GALT was associated with less
      immune activation and lower markers of microbial translocation, whereas
      regulatory T cell frequency showed positive associations with immune activation.
      We hypothesized that the composition of the microbiota would influence iNKT cell
      frequency and function. We found positive associations between the abundance of
      several Bacteroides species and iNKT cell frequency and their capacity to produce
      IL-4 in the GALT but not in the blood. Overall, our results are consistent with
      the hypothesis that GALT iNKT cells, influenced by certain bacterial species, may
      have a key role in regulating immune activation in HIV-1 infection.

PMID- 27049062
TI  - MAIT cells reside in the female genital mucosa and are biased towards IL-17 and
      IL-22 production in response to bacterial stimulation.
AB  - The female genital tract (FGT) mucosa is a critically important site for immune
      defense against microbes. Mucosal-associated invariant T (MAIT) cells are an
      innate-like T-cell population that recognizes microbial riboflavin metabolite
      antigens in an MR1-dependent manner. The role of MAIT cells in the FGT mucosa is
      unknown. Here, we found that MAIT cells and MR1+ antigen-presenting cells were
      present in the upper and lower FGT, with distinct tissue localization of MAIT
      cells in endometrium vs. cervix. The MAIT cells from the FGT and blood displayed
      a distinct phenotype with expression of interleukin (IL)-18Ralpha, CD127,
      alpha4beta7, PD-1, as well as the transcription factors promyelocytic leukemia
      zinc finger (PLZF), RORgammat, Helios, Eomes, and T-bet. Their expression levels
      of PLZF and Eomes were lower in the FGT compared with blood. When stimulated with
      Escherichia coli, MAIT cells from the FGT displayed a bias towards IL-17 and IL
      22 expression, whereas blood MAIT cells produced primarily IFN-gamma, TNF, and
      Granzyme B. Furthermore, both FGT- and blood-derived MAIT cells were
      polyfunctional and contributed to the T-cell-mediated response to E. coli. Thus,
      MAIT cells in the genital mucosa have a distinct IL-17/IL-22 profile and may have
      an important role in the immunological homeostasis and control of microbes at
      this site.

PMID- 27049063
TI  - Eosinophils subvert host resistance to an intracellular pathogen by instigating
      non-protective IL-4 in CCR2-/- mice.
AB  - Eosinophils contribute to type II immune responses in helminth infections and
      allergic diseases; however, their influence on intracellular pathogens is less
      clear. We previously reported that CCR2-/- mice exposed to the intracellular
      fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an
      early exaggerated interleukin (IL)-4 response. We sought to identify the cellular
      source promulgating IL-4 in infected mutant animals. Eosinophils were the
      principal instigators of non-protective IL-4 and depleting this granulocyte
      population improved fungal clearance in CCR2-/- animals. The deleterious impact
      of eosinophilia on mycosis was also recapitulated in transgenic animals
      overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed
      that phagocytosis of H. capsulatum via the pattern recognition receptor
      complement receptor (CR) 3 triggered the heightened IL-4 response in murine
      eosinophils. This phenomenon was conserved in human eosinophils; exposure of
      cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings
      elucidate a detrimental attribute of eosinophil biology in fungal infections that
      could potentially trigger a collapse in host defenses by instigating type II
      immunity.

PMID- 27049064
TI  - Rosette-forming glioneuronal tumor of the thalamus.

PMID- 27049065
TI  - Intracranial solitary fibrous tumor/ hemangiopericytoma with osteoclast-like
      multinucleated giant cells: comparison with giant cell-rich solitary fibrous
      tumor.
AB  - AIMS: Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a
      mesenchymal neoplasm that typically presents in adults as a dural-based lesion.
      The presence of giant cells in these tumors is a rare occurrence. MATERIALS AND
      METHODS: We studied a case of intracranial SFT/HPC with unusual multinucleated,
      osteoclast-like giant cells and compared it to the so-called giant cell
      angiofibroma (i.e., giant cell-rich solitary fibrous tumor) withattention to
      STAT6 immunohistochemistry. RESULTS: A 73-year-old man developed a right
      frontoparietal dural mass that was completely resected. Histology demonstrated a
      hypercellular neoplasm consisting of spindle to oval cells and scattered
      osteoclast-like multinucleated giant cells (MGCs), with distinctive "staghorn"
      blood vessels. Necrosis and brisk mitotic activity were present. The spindle cell
      component showed strong focal CD34 and nuclear STAT6 immunohistochemical
      labeling, while CD68 and CD163 were positive in MGCs. No nuclear STAT6 reactivity
      was detected in MGCs. By contrast, nuclear STAT6 staining was present in three
      cases of giant cell angiofibroma (i.e., giant-cell rich solitary fibrous tumor),
      both in the spindle cell component and MGCs. CONCLUSION: Intracranial SFT/HPC is
      characterized by nuclear STAT6 immunoreactivity as its soft tissue counterparts.
      The presence of osteoclast-like MGCs is an unusual finding in this neoplasm,
      which is distinct from giant cell-rich solitary fibrous tumor.

PMID- 27049066
TI  - Morphometric characterization of brain arteriovenous malformations for clinical
      and radiological studies to identify silent intralesional microhemorrhages.
AB  - Brain arteriovenous malformations (bAVMs) are vascular lesions that can cause
      significant morbidity and mortality, particularly when they bleed, i.e., rupture.
      Determining the risk of rupture for bAVMs is a crucial task to determine the most
      appropriate approach to patients with bAVM. Furthermore, patients who present
      with a hemorrhagic event also have a higher risk of subsequent hemorrhage.
      Determination of the hemorrhage risk and management strategy for incidentally
      discovered bAVMs still remains a controversial subject. In recent years, we have
      identified silent intralesional microhemorrhages (SIMs) as a possible risk factor
      for subsequent hemorrhage in patients with bAVMs. The principal aim of this study
      was to determine critical histological features that can be correlated with
      preoperative radioimaging findings, and allow better identification of patients
      with greater risk of adverse outcome. Here we provide a detailed descriptive
      analysis of the morphometric assessment of bAVMs in order to provide reproducible
      methodology that will aid in correlating preoperative radioimaging findings with
      histological features that may be significantly associated with increased risk of
      hemorrhage/rupture. 

PMID- 27049067
TI  - Identification and characterization of histone lysine methylation modifiers in
      Fragaria vesca.
AB  - The diploid woodland strawberry (Fragaria vesca) is an important model for fruit
      crops because of several unique characteristics including the small genome size,
      an ethylene-independent fruit ripening process, and fruit flesh derived from
      receptacle tissues rather than the ovary wall which is more typical of fruiting
      plants. Histone methylation is an important factor in gene regulation in higher
      plants but little is known about its roles in fruit development. We have
      identified 45 SET methyltransferase, 22 JmjC demethylase and 4 LSD demethylase
      genes in F. vesca. The analysis of these histone modifiers in eight plant species
      supports the clustering of those genes into major classes consistent with their
      functions. We also provide evidence that whole genome duplication and dispersed
      duplications via retrotransposons may have played pivotal roles in the expansion
      of histone modifier genes in F. vesca. Furthermore, transcriptome data
      demonstrated that expression of some SET genes increase as the fruit develops and
      peaks at the turning stage. Meanwhile, we have observed that expression of those
      SET genes responds to cold and heat stresses. Our results indicate that
      regulation of histone methylation may play a critical role in fruit development
      as well as responses to abiotic stresses in strawberry. 

PMID- 27049068
TI  - Mental health outcomes of burn: A longitudinal population-based study of adults
      hospitalized for burns.
AB  - PURPOSE: This study investigates the increased risk of mental health outcomes and
      health care utilization associated with burn with two year of follow-up using a
      longitudinal population-based matched cohort design. METHODS: Adult burn
      survivors (n=157) were identified from a provincial burn registry and matched 1:5
      with non-burn control subjects from the general population (matching variables
      age and gender). The prevalence of mental health outcomes and the rates of health
      care utilization between the groups were compared for the 2years pre and post
      index date using anonymously linked population-based administrative health care
      data. Rates were adjusted for age, gender and sociodemographic characteristics.
      RESULTS: While the burn cohort had an increased prevalence of mental health
      problems after burn compared to the control cohort, the burn group also had an
      increased prevalence of pre-burn depression (16.6% vs 7.8%; p=0.0005) and
      substance use disorders (8.9% vs 3.2%; p=0.001) when compared to controls. Once
      the pre-existing prevalence of mental illness was taken into account there was no
      significant change in the prevalence of mental health problems when comparing the
      burn group to controls over time. CONCLUSIONS: Although burns may not increase
      rates of mental health issues and health care utilization, burn survivors are a
      vulnerable group who already demonstrate increased rates of psychopathology and
      need for care. The present study highlights the importance of assessment and
      treatment of mental health outcomes in this population.

PMID- 27049069
TI  - The release of Doxorubicin from liposomes monitored by MRI and triggered by a
      combination of US stimuli led to a complete tumor regression in a breast cancer
      mouse model.
AB  - The work aimed at developing a novel MRI-based theranostic protocol for improving
      the anticancer efficacy of a Doxil-like liposomal formulation. The goal was
      achieved stimulating the intratumor release of the drug from the nanocarrier and
      favoring its diffusion in the lesion by the sequential application of low
      intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic
      breast cancer model. The combination of acoustic waves with different
      characteristics allowed for: i) the release of the drug and the co-encapsulated
      MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region,
      and ii) the extravasation of the released material, as well as intact liposomes,
      in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor
      reported on the delivery and US-triggered release of Doxorubicin. The developed
      protocol resulted in a marked increase in the intratumor drug concentration that,
      in turn, led to the complete regression of the lesion. The protocol has a good
      clinical translatability because all the components of the theranostic agent
      (Doxorubicin, liposomes, Gadoteridol) are approved for human use.

PMID- 27049070
TI  - C-reactive protein correlates to functional score systems of patients in general
      surgical intensive care unit.
AB  - The aim of our study was to document the relationship between inflammation
      indicated by the serum levels of widespread acute-phase proteins and scoring
      systems used in assessing patient?s functional condition. We therefore assessed
      serum levels of c-reactive protein (CRP) and four clinical tests [acutephysiology
      and chronic health evaluation (APACHE) II score and sequential organ failure
      assessment (SOFA) score, functional independence measure (FIM) and Barthel index
      of activities of daily living (BI)]. We tested the hypothesis that results of
      functional tests correlate with infections and consecutively influence the length
      of stay (LOS) in non-specialized general intensive care units (ICUs). One hundred
      and twenty patients from non-specialized general ICU were enrolled in the study
      group. We scored patients consecutively on admission (APACHE II-initial; SOFA
      initial, FIM initial and BI initial) and on the fifth day of stay (APACHE II-5th
      day; SOFA-5th day, FIM 5th day and BI 5th day). At the same time points, serum
      levels of CRP were assessed. FIM index did not correlate to the CRP at any time
      point (FIM- initial=0.027; FIM- 5th day=0.024; respectively) at discharge, total
      number of hospital days, i.e. LOS was recorded. Serum CRP values and APACHE II,
      SOFA, and BI scores correlated positively both on admission and on the fifth day
      of stay in the general surgical ICU (APACHE II- initial r=0.289; SOFA- initial
      r=0.305; BI - initial r=0.291; APACHE II 5th day r=0.728; SOFA-5th day r=0.725;
      BI 5th day r=0.792). Therefore, pending further studies, functional scoring in
      general surgical ICUs might prove useful in assessing LOS. 

PMID- 27049071
TI  - Use, abuse and misuse of biomarkers in paediatrics.
AB  - Currently, a gold standard for distinguishing between infectious, inflammatory,
      auto-immune diseases and malignancy in infants and children is not available. The
      combination of biomarkers with clinical features and other diagnostic tests could
      help clinicians in the diagnostic process. Ideally, a biomarker should have high
      sensitivity, specificity, and predictive value, as well as being easily obtained
      also in preterm babies and infants, requiring a small amount of blood and being
      quickly measured. The available literature agrees on the fact that a ?perfect?
      biomarker is not currently available in paediatric practice. Thus, clinicians
      must consider time by time the balance between marker characteristics and their
      sensitivity and specificity in different conditions. The development of new tests
      with higher sensitivity and specificity in distinguishing different pathological
      situations is auspicable. Moreover, future efforts should be focused on
      validating also in children the recently developed biomarkers including CD64, IL
      27 and IL-8. 

PMID- 27049072
TI  - Is vitamin E an anti-allergic compound?
AB  - Vitamin E is found in eight forms in nature which include four tocopherols
      (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and
      delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to
      the tissue and is useful for the treatment of pain, inflammation and allergic
      reactions. In addition to antioxidant activity, vitamin E also has a number of
      different and related functions. It protects against cancer, improves immune
      response, lowers the incidence of infectious diseases, cardiovascular diseases
      and is protective in allergy and asthma risk, and other disorders. Vitamin E
      increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect
      that diminishes asthma and allergic diseases. Moreover, vitamin E regulates
      vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through
      its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the
      endothelial function by altering VCAM-1-induced oxidative activation of
      endothelial cell PKCalpha. However, vitamin E is not consistently associated with
      asthma and/or allergy, and in some cases there are conflicting results on allergy
      and inflammatory diseases. The association of vitamin E and allergy appears to be
      very complex, and further study needs to clarify this dilemma. 

PMID- 27049073
TI  - Peripheral blood-derived, gamma9delta2 t cell-enriched cell lines from
      glioblastoma multiforme patients exert anti-tumoral effects in vitro.
AB  - The goal of this work was to assess the potential of T cells expressing
      Vgamma9Vdelta2+ T cell receptors (TCR, gamma9delta2T cells) present in peripheral
      blood (PB) m ononuclear cells (MC, PBMC) of glioblastoma multiforme (GBM)
      patients to act as anti-tumoral agents. We found that gamma9delta2T cell levels
      were decreased in patients' PB relative to a cohort of healthy donors (HD)
      (respectively 0.52+/-0.55%, n=16, vs 1.12+/-0.6%, n=14, p=0.008) but did not
      significantly correlate with postoperative survival (R=0.6, p=0.063).
      Importantly, however, the gamma9delta2T cells could be expanded in vitro to
      consist 51+/-23% of the cultured lymphocytes (98% CD3+). This was achieved after
      14 days of culture in medium containing the amino-bisphosphonate (ABP)
      Zoledronate (Zol) and interleukin (IL)-2, resulting in gamma9delta2T cell
      enriched lines (gdTCEL) similar to those of HD derived gdTCEL (54+/-19%).
      Moreover, gdTCEL from patients and HD mediated cytotoxicity to GBM-derived cell
      lines (GBMDCL), which was abrogated by immune-magnetic removal of the
      gamma9delta2T cells. Furthermore, low level interferon (IFN) gamma secretion was
      induced by gdTCEL briefly co-cultured with GBMDCL or autologous - tumor-derived
      cells, which was greatly amplified in the presence of Zol. Importantly, IFNgamma
      secretion was inhibited by mevastatin but enhanced by cross-linking of
      butyrophilin 3A1 (CD277) on a CD277+ GBMDCL (U251MG) or by pretreatment of GBMDCL
      with temozolomide (TMZ). Taken together, these data suggest that gamma9delta2T
      cells in PB of GBM patients can give rise to gdTCEL that mediate anti-tumoral
      activities. 

PMID- 27049074
TI  - The role of NADPH-derived reactive oxygen species production in the pathogenesis
      of endometriosis: a novel mechanistic approach.
AB  - Endometriosis is defined as endometriotic tissue growing outside the uterine
      cavity. It is a common gynecological disorder in women of reproductive age and is
      associated with chronic pelvic pain and infertility. Despite several studies and
      theories to explain its cause, the exact pathogenesis of endometriosis remains
      unclear. Retrograde menstruation is the most plausible theory, however, it is not
      exclusive. The disparity between the actual prevalence of retrograde menstruation
      and the prevalence of endometriosis suggests that other factors may determine the
      susceptibility to endometriosis development. Oxidative stress has been associated
      with endometriosis. This study aimed to explore the role of NADPH oxidase family
      in the production of reactive oxygen species (ROS) and to determine whether ROS
      induce the proliferation of endometriotic implants via mammalian target of
      rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected
      from women undergoing laparoscopy for endometriosis. The samples were stained
      with dihydroethidium and fluorescent images of the slides were taken to detect
      ROS production. After extraction of RNA from the samples and c-DNA generation,
      quantitative real-time PCR, protein extraction and Western blot were performed to
      study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and
      fibronectin. The results showed an increase in ROS levels and NOX 1 gene and
      protein expression in the endometriotic tissues compared to the normal
      surrounding tissue control. Also, mTOR and fibronectin, gene expression was found
      to be increased. Up regulation of NOX at gene and protein level leads to
      increased production of ROS in the endometriotic tissue, which in turn causes
      proliferation of the ectopic tissue via alteration of the mTOR signaling pathway.
      Increased fibronectin gene expression points towards tissue injury in
      endometriosis as compared to the normal surrounding tissue. This manuscript adds
      a new insight into the pathogenesis of endometriosis and serves as a background
      for development of new treatments for the disease-associated pain and
      infertility. 

PMID- 27049075
TI  - Penehyclidine hydrochloride postconditioning ameliorates cerebral ischemia
      reperfusion injury: critical role of mitochondrial ATP sensitive potassium
      channel.
AB  - Cerebral ischemia/reperfusion (CI/R) leads to disability and death worldwide.
      However, limited approaches have been made in developing therapies to decrease
      the detrimental effects of CI/R. In the present study, we evaluated the effects
      of penehyclidine hydrochloride (PHC) postconditioning on CI/R injury and
      elucidated the underlying mechanisms. In CI/R rats, we showed that PHC
      postconditioning could effectively inhibit I/R-induced brain infarction and
      edema, and deficit of neurological function. In addition, PHC postconditioning
      significantly inhibited I/R-induced increase of proinflammatory cytokines and
      TUNEL-positive cell numbers. Moreover, the opening of mitochondrial permeability
      transition pore (mPTP) and oxidative stress resulting from I/R were suppressed
      notably by PHC postconditioning, as evidenced by increased absorbance at 540 nm
      in Ca2+-induced mitochondrial swelling test and increased SOD activity and
      decreased ROS and MDA level. 5-hydroxydecanoate (5-HD), a specific inhibitor of
      MitoKATP, was used to evaluate the role of MitoKATP in the neuroprotective effect
      of PHC postconditioning. The results showed that 5-HD could markedly suppress PHC
      postconditioning-caused inhibition of brain infarction and edema, deficit of
      neurological function, inflammation, apoptosis, opening of mPTP and oxidative
      stress induced by CI/R. The results demonstrated that PHC postconditioning could
      protect against I/R injury in brain through the inhibition of oxidative stress,
      mPTP opening, apoptosis and inflammation. Activation of MitoKATP was critical for
      PHC postconditioning-exhibited neuro-protective effects against I/R injury. These
      findings may provide a novel foundation for therapeutic strategies targeting
      cerebral protection against I/R damage. 

PMID- 27049076
TI  - Silencing of myeloid cell leukemia-1 by small interfering RNA improves
      chemosensitivity to etoposide in u-937 leukemic cells.
AB  - A key issue in the treatment of acute myeloid leukemia (AML) is the development
      of drug resistance to chemotherapeutic agents. Overexpression of myeloid cell
      leukemia-1 (Mcl-1), an anti-apoptotic protein, is associated with tumor
      progression and drug resistance in leukemia and several cancers. The purpose of
      this study was to investigate the effect of specific Mcl-1 small interference RNA
      (siRNA) on the proliferation and chemosensitivity of U-937 AML cell to etoposide.
      The siRNA transfection was conducted using Lipofectamine? 2000. Quantitative real
      time RT-PCR (qRT-PCR) and Western blot analysis were employed to measure the
      expression levels of mRNA and protein, respectively. To evaluate tumor cell
      growth after siRNA transfection, Trypan blue exclusion assay was conducted. The
      cytotoxic effects of siRNA and etoposide were determined using MTT assay on their
      own and in combination. DNA-histone ELISA and annexin-V/FITC assays were
      performed to study the apoptosis. Mcl-1 siRNA transfection significantly blocked
      the expression of Mcl-1 mRNA and protein in a time-dependent manner, leading to a
      strong growth inhibition and enhanced apoptosis (P less than 0.05). Furthermore,
      pretreatment with Mcl-1 siRNA, synergistically enhanced the cytotoxic and
      apoptotic effects of etoposide (P less than 0.05). Our results demonstrated that
      Mcl-1 plays a fundamental role in the survival and resistance of U-937 cells to
      etoposide. Therefore, Mcl-1 can be considered an attractive target in gene
      therapy of AML patients and siRNA-mediated silencing of this gene may be a novel
      strategy in AML treatment. 

PMID- 27049077
TI  - Effects of epidural block combined with general anesthesia on antitumor
      characteristics of T helper cells in hepatocellular carcinoma patients.
AB  - This study discusses the changes of T helper cells (Th cells) of patients who
      received different anesthesia methods in liver cancer resection. We selected 122
      patients who were diagnosed with hepatocellular carcinoma and underwent liver
      cancer resection and divided them into a general anesthesia combined with
      epidural anesthesia group (group A) and general anesthesia group (group B).
      Peripheral blood was collected to detect Th cells on the day of surgery, and on
      the second and seventh days after surgery. Th1 and Th2 cell frequency and mRNA
      expression of interferon-gamma (IFN-gamma) of all patients significantly rose on
      the second day but recovered to the previous level on the seventh day. Th1/Th2
      increased remarkably on the seventh day compared to the second day. Compared to
      the day of surgery, Th17, regulatory T (Treg)cells as well as mRNA expression of
      interleukin-17 (IL-17) and FoxP3 had no obvious changes on the second day, but
      dramatically declined on the seventh day. Compared to group B, Th1 cell frequency
      and Th1/Th2 in group A had a slight increase on the second day, and a remarkable
      increase on the seventh day; but Th2, Th17 and Treg cell frequency in group A
      slightly decreased on the second day and remarkably decreased on the seventh day.
      mRNA of IFN-gamma, cytokine levels and IFN-gamma/IL-4 of group A were all higher
      than group B on the seventh day, while mRNA of IL-17, concentration of IL-17 as
      well as concentration of transforming growth factor-beta1 (TGF-beta1) in group A
      were much lower than group B. These findings suggest that improving antitumor
      activity of Th cells can benefit patients who receive liver cancer resection. 

PMID- 27049078
TI  - A novel quantitative method of pten expression assessment in tumor tissue.
AB  - Phosphatase and Tensin Homolog deleted on chromosome 10 (PTEN) gene is one of the
      most important tumor suppressor genes which is involved in the regulation of many
      signaling cascades (AKT/PKB and MAPK). Subtle changes in its activity lead to
      cancer susceptibility or aggressive tumor behaviour. Despite the diversity of
      mechanisms leading to PTEN inactivation, it is frequently associated with a
      decreased or complete loss of protein expression. About 20% decrease in PTEN
      expression could lead to the development of cancer. There have been no objective,
      quantitative methods of PTEN expression assessment that allow to measure the
      subtle variations of the protein concentration in a tissue-contextual manner. A
      new quantitative algorithm of immunostaining evaluation based on combination of
      color deconvolution and relative chromogen signal intensity was used in the
      study. The proposed algorithm was implemented in the popular ImageJ image
      analysis software and positively verified in cancer cell lines and tissue models
      as well as in the tissue samples of colorectal cancer (CRC) patients. The
      proposed quantitative method of PTEN expression assessment creates an alternative
      to currently available subjective methods and forms the basis for inter-case and
      inter-tissue comparisons. Using the algorithm it would be possible to identify
      three groups of patients with advanced colorectal cancer which could
      significantly differ in the overall survival. The research should be continued. 

PMID- 27049079
TI  - Influence of continuous intervention on growth and metastasis of human cervical
      cancer cells and expression of RNAmiR-574-5p.
AB  - This study was carried out to acquire solid evidence that some common treatments
      could affect micro ribonucleic acids (miRNAs) by revealing the regulatory effect
      of genes, so as to provide a reference for further exploration of the prevention
      and treatment of cervical cancer. Nude mouse tumorigenicity assay was used to
      study the effect of inhibiting miR-574-5p on development and tumorigenic ability
      of Henrietta Lacks (HeLa) tumor. Cell wound scratch assay, flow cytometry and
      real-time quantitative polymerase chain reaction (RT-qPCR) were adopted to study
      the effects of anoxia and temperature, etc., on expression of miR-574-5p and QKI
      in HeLa as well as on the clone and migration ability of cells, to provide
      prevention and treatment of cervical cancer with new ideas and evidence. The
      results demonstrated that cervical cancer tissues had a significantly increased
      miR-574-5p expression compared with para-carcinoma tissues; conversely, Gomafu,
      overall QKI (pan-QKI) and QKI-5 messenger ribonucleic acid (mRNA) and protein
      expression all decreased. Part of the common nursing methods had a certain
      influence on miR-574-5p expression, HeLa reproduction and metastasis, and even
      cell cycle. For example, ultraviolet (UV) irradiation was effective in decreasing
      miR-574-5p expression of HeLa and inhibiting cell migration; severe hypoxia
      significantly decreased the survival rate of HeLa, leading to the increase of
      programmed death percentage and cell ratio in G2/M phase as well as the decrease
      of cell ratio in G1 phase. Incubation at different temperatures also affected miR
      574-5p expression and cell proliferation. Thus, it can be known that miR-574-5p,
      Gomafu and QKI expression in cervical cancer tissues and para-carcinoma tissues
      are significantly up-regulated or down-regulated. Some treatments, such as UV
      irradiation, hypoxia, incubation temperatures, etc., can affect miR-574-5p
      expression and HeLa proliferation as well as metastases in different degrees.
      These findings provide a reference and basis for further study. 

PMID- 27049080
TI  - Expression of cartilage antitumor component RanBP9 in osteosarcoma.
AB  - This study was carried out to investigate the expression changes of RanBP9 in
      tissue specimens and osteosarcoma cell strains and preliminarily explore its
      mechanism in osteosarcoma, so as to provide a theoretical foundation for follow
      up experiments. The expression of RanBP9 in human osteosarcoma tissue specimens
      was detected by immunohistochemistry and the expression of RanBP9 messenger
      ribose nucleic acid (mRNA) in osteosarcoma cell strains was detected in real-time
      with polymerase chain reaction (PCR), and finally the expression of RanBP9
      protein in osteosarcoma cell strains was detected by immunofluorescent staining
      and Western blot. Results demonstrated that RanBP9 was widely expressed in
      tissues, but also highly expressed in cells; moreover, the expression of RanBP9
      was mainly concentrated in cytoplasm and nucleus, and partial expression was
      found in cell membrane. Thus, it can be concluded that RanBP9 is positively
      expressed in bone tumor tissues and cell strains. 

PMID- 27049081
TI  - Adipose-derived mesenchymal stromal (stem) cells differentiate to osteoblast and
      chondroblast lineages upon incubation with conditioned media from dental pulp
      stem cell-derived osteoblasts and auricle cartilage chondrocytes.
AB  - The potential of adipose-derived mesenchymal stromal (stem) cells (ADSCs) to
      differentiate into either osteoblasts or chondrocytes is controversial. In this
      study we investigated the multicapacity potential of ADSCs to differentiate
      towards adipocyte, osteoblast, and chondrocyte lineages when cells are seeded
      onto plastic in comparison with incubation with conditioned media (CM) obtained
      from differentiated cell types.ADSCs, obtained from liposuctions, were
      characterized for mesenchymal and hematopoietic markers by cytofluorimetry. Their
      differentiation capacity towards adipocytes, osteoblasts, and chondrocytes was
      investigated by histochemistry methods (Oil-Red-O staining, Safranin O and
      Alizarin Red staining, respectively). Dental pulp stem cells (DPSCs) and
      dedifferentiated auricle derived-chondrocytes were differentiated towards
      osteoblastic and chondrocytic lineages respectively, and the CM obtained from
      these cultures was used to induce differentiation of ADSCs. ADSCs were positive
      for mesenchymal markers (CD29, CD105, CD73, CD44), but not for hematopoietic
      lineage markers (CD14, CD34, CD45) and this behavior was conserved from the
      isolation up to the fifth passage. While ADSCs were readily differentiated in
      adipocytes, they were not towards chondrocytes and osteoblastic lineages, a
      behavior different from that of bone marrow-derived MSCs that differentiated into
      the three lineages at two weeks post-induction. Only ADSCs treated with CM from
      cultured chondrocytes and DPSCs, produced glycosaminoglycans and mineralized
      matrix. These results indicate that ADSCs need growth/morphogenic factor
      supplementation from the tissue environment to be appropriately differentiated to
      mesodermic lineages. 

PMID- 27049082
TI  - Decreased serum levels of T-cell immunoglobulin mucin-1 and T-cell immunoglobulin
      mucin-3 in systemic lupus erythematosus patients.
AB  - This study aims to investigate the serum T-cell immunoglobulin mucin (TIM)-1 and
      TIM-3 levels in systemic lupus erythematosus (SLE) patients and analyze their
      correlations with clinical features. Sixtyone SLE patients and 69 healthy
      controls were enrolled, serum TIM-1 and TIM-3 levels were detected by ELISA.
      Results demonstrated that both serum TIM-1 and TIM-3 levels were significantly
      decreased in SLE patients compared with controls (both P less than 0.05). Lower
      serum TIM-3 levels in SLE patients with nephritis were observed when compared to
      those without nephritis, with a marginal statistical significance (P=0.059).
      However, both serum TIM-1 and TIM-3 levels had no significant correlation with
      SLE disease activity (both >0.05). In summary, decreased serum TIM-1 and TIM-3
      levels and association of TIM-3 with nephritis suggest their possible role in the
      development and pathogenesis of SLE. However, further studies are needed to
      confirm these preliminary results. 

PMID- 27049083
TI  - Doppler laser imaging predicts response to topical minoxidil in the treatment of
      female pattern hair loss.
AB  - Topical minoxidil is the only drug approved by the US FDA for the treatment of
      female pattern hair loss. Unfortunately, following 16 weeks of daily application,
      less than 40% of patients regrow hair. Several studies have demonstrated that
      sulfotransferase enzyme activity in plucked hair follicles predicts topical
      minoxidil response in female pattern hair loss patients. However, due to
      patients? discomfort with the procedure, and the time required to perform the
      enzymatic assay it would be ideal to develop a rapid, non-invasive test for
      sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active
      form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of
      hair. Minoxidil sulfate is the active form required for both the promotion of
      hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized
      that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to
      the application of topical minoxidil would correlate with sulfotransferase enzyme
      activity in plucked hair follicles. In this study, plucked hair follicles from
      female pattern hair loss patients were analyzed for sulfotransferase enzyme
      activity. Additionally, laser Doppler velocimetry was used to measure the change
      in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of
      minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0)
      between the change in scalp perfusion within 60 minutes after topical minoxidil
      application and sulfotransferase enzyme activity in plucked hairs. To our
      knowledge, this is the first study demonstrating the feasibility of using laser
      Doppler imaging as a rapid, non-invasive diagnostic test to predict topical
      minoxidil response in the treatment of female pattern hair loss. 

PMID- 27049084
TI  - Effects of sodium ferrous chlorophyll treatment on anemia of hemodialysis
      patients and relevant biochemical parameters.
AB  - This study explores the effects of sodium ferrous chlorophyll treatment on the
      anemia of maintenance hemodialysis (MHD) patients, as well as the relevant
      biochemical parameters. We selected 72 patients who had received regular MHD
      treatment two or three times a week for more than 3 months in the Hospital of
      Traditional Chinese Medicine of Zhengzhou City of Henan Province from March 2014
      to March 2016. They were equally divided into a treatment group and a control
      group. Haemoglobin (HB) and hematocrit (HCT) of the treatment group increased
      significantly after treatment (p < 0.01), but less in the control group (p <
      0.05); Also serum ferritin (SF) and transferrin saturation (TAST) of the
      treatment group increased significantly after treatment (p < 0.01); SF of the
      control group also increased significantly (p < 0.01) and TAST of the control
      group increased (p < 0.05) but less than in the treatment group. No obvious
      changes of serum creatinine (SCR), blood urea nitrogen (BUN), C-reactive protein
      (CRP) and superoxide dismutase (SOD) were found in either groups after treatment
      (p>0.05). Albumin (ALB) dosage of the treatment group increased after treatment
      (p < 0.05) while hemopoietin (EPO) decreased significantly (p < 0.01). ALB and
      EPO of the control group had no obvious changes after treatment (p>0.05). ALB
      level of the treatment group increased more significantly than in the control
      group (p < 0.05), while EPO dosage decreased more significantly than in the
      control group (p <0.05). Therefore, the combination of conventional western
      medicine and sodium ferrous chlorophyll can effectively improve anemia conditions
      of MHD patients and their quality of life.

PMID- 27049085
TI  - Curative effect of mechanical heart valve replacement and anticoagulant therapy
      after surgery.
AB  - This study was carried out to determine the curative effect of low-intensity
      anticoagulant therapy by observing the oral administration of warfarin
      (anticoagulant therapy) on patients who had undergone mechanical heart valve
      replacement (MHVR) surgery with subsequent anticoagulation complications. Fifty
      patients who underwent MHVR in the Second Affiliated Hospital of Harbin Medical
      University and 52 patients in the Cardiovascular Surgery of Daqing Oilfield
      General Hospital between January 2013 and January 2016 were selected (63 males
      and 39 females, ages 26-77 years). They took warfarin after treatment and were
      followed-up by means of outpatient review and telephone after leaving the
      hospital. The effect of warfarin and the occurrence of anticoagulation
      complications were analyzed. The operations lasted 230+/-106 min, extracorporeal
      circulation for 110+/-50 min and aorta occlusion for 82+/-23 min. During post
      operation 3 patients developed skin purpura and one patient died. During follow
      up we found 3 cases of anemia caused by excessive menstruation, 4 cases of
      hematuresis, 3 cases of peated epistaxis, 1 case of gastrointestinal bleeding, 1
      case of cerebral hemorrhage, 1 case of embolism in the lower limbs and 1 case of
      cerebral infarction, although they all improved or were totally cured. Therefore,
      the incidence of complications can be reduced significantly by the correct
      administration of warfarin as well as timely monitoring of interference factors
      after MHVR. 

PMID- 27049086
TI  - Effects of Wuzhi capsule on blood concentration of tacrolimus after renal
      transplantation.
AB  - This study aimed to investigate the effects of Wuzhi capsule on blood
      concentration of tacrolimus after renal transplantation. Sixty patients after
      allogenic renal transplantation were enrolled in this study and randomly divided
      into an experimental group and a control group. One oral Wuzhi capsule was taken
      in the morning and evening for patients in the experimental group, while none was
      given to the control group, maintaining the trough blood concentration of
      tacrolimus in the normal range. After 3 weeks, the changes of tacrolimus dosage
      and hepatorenal function in the two groups were compared. Comparisons of drug
      dosage and blood concentration C0 value of tacrolimus before initiating the
      experiment showed that there was no statistically ignificant difference (P>0.05)
      between the two groups. The differences of blood concentration of tacrolimus and
      hepatorenal function for patients in both two groups after 3 weeks? treatment
      also showed no statistical significance (P>0.05), whereas a statistically
      significant decrease was demonstrated in the tacrolimus dosage of the Wuzhi
      capsule group compared with that of the control group (P=0.0083). After renal
      transplantation, Wuzhi capsules were added so as to enable tacrolimus to reach a
      suitable blood concentration, which can prevent the occurrence of renal
      transplantation rejection, thus alleviating the economic burden of patients and
      producing larger social benefits. 

PMID- 27049087
TI  - Lipedema ? lack of evidence for the involvement of tyrosine kinases.
AB  - Lipedema is a chronic disorder characterized by abnormal distribution of
      subcutaneous adipose tissue on the proximal extremities, pain and capillary
      fragility. Its etiology is unknown but in analogy to central obesity, chronic low
      level inflammation in adipose tissue has been suggested. There seems to be an
      increased propagation of pre-adipocytes into mature adipocytes contributing to
      the massive enlargement of subcutaneous adipose tissue. We investigated whether
      tyrosine kinases might be involved. Proteins from adipose tissue harvested during
      microcannular tumescent liposuction in lipedema and in lipomas were subjected to
      10% polyacrylamide-gel, transferred to a polyvinylidenfluorid membrane and
      immunoblotted with indicated P-Tyr-100 antibody followed by enhanced
      chemiluminescence reaction. A survey of all blots did not reveal tyrosine
      phosphorylated proteins with a molecular weight >100 kD in lipedema tissue and
      controls. These investigations suggest absence of activated growth factor
      receptors. Some signals indicating unspecific tyrosine-phosphorylation of smaller
      proteins were detected in tissue of both lipedema patients and controls. The
      present data suggest that there is no enduring activation of tyrosine kinase
      pathways of adipogenesis in lipedema as in lipoma controls. 

PMID- 27049088
TI  - Expression profiles of SMAD1 protein in lung cancer tissues and normal tissues
      and its effect on lung cancer incidence.
AB  - The aim of this study is to detect the expression profiles of SMAD1 protein in
      lung cancer tissues and normal tissues to investigate its effect on the incidence
      of lung cancer. The expression profiles of SMAD1 protein in 60 cases of lung
      cancer tissues (lung cancer group), 25 cases of normal alveolus tissues (alveolus
      control group) and 29 cases of normal bronchial tissues (bronchial control group)
      were detected by adopting immunohistochemical analyses, and their relationships
      with clinicopathologic data were analyzed. The expression of SMAD1 protein in the
      lung cancer group and the lung squamous cell carcinoma group was significantly
      lower than that in the alveolus control group and the bronchial control group (P
      < 0.01). The expression of SMAD1 protein in the lung adenocarcinoma group was
      significantly lower than that in the alveolus control group and the bronchial
      control group (P < 0.01); The expression SMAD1 protein showed a significant
      correlation with lung cancer differentiation and lymphatic metastasis (P < 0.05),
      but not with genders, ages, tumor sizes and histological types of lung cancer
      patients (P>0.05).

PMID- 27049089
TI  - Total hip replacement for developmental dysplasia of hip and postoperative
      nursing.
AB  - This study was designed to determine the clinical effect of total hip replacement
      for the treatment of developmental dysplasia of the hip (DDH) and analyze the
      postoperative nursing. Sixty patients (78 hips) aged 18-75 years (average 58.6+/
      2.31 years) who received total hip replacement for treatment of DDH at the
      Zhengzhou People?s Hospital, Henan, China, from April 2013 to June 2016 were
      selected as research subjects. Twenty-four patients were male (30 hips) and 36
      were female (48 hips). Of the 60 patients, according to Crowe typing, 24 were
      type I (30 hips), 26 were type II (34 hips), 6 were type III (8 hips) and 4 were
      type IV (6 hips). According to the Harris hip score system, the score of all hips
      was 39.46+/-3.56 points average (18-56 points) before treatment and resulted as
      89.60+/-4.25 points (79-98 points) at the last follow-up, showing a statistically
      significant difference (P < 0.05). Complications such as wound infection,
      dislocation, fracture of femoral shaft, femoral nerve and injury of sciatic nerve
      were not found after treatment. A total of 48 cases (58 hips) obtained excellent
      curative results (93.33% recovery), 8 cases (14 hips) good (92.31% recovery), and
      4 cases (6 hips) medium. Total hip replacement proved to be effective in treating
      DDH and secondary osteoarthritis. Moreover, soft tissue release and an optimum
      degree recovery of anatomic form and physiological function of the diseased hip
      is an important basis for reconstructing the acetabulum and stabilizing
      acetabulum prosthesis.

PMID- 27049090
TI  - Relationship between serum interleukin-17 level and inflammatory bowel disease.
AB  - By detecting expression of interleukin (IL)-17A, IL-10 and interferon-gamma (IFN
      gamma) in serum of inflammatory bowel disease (IBD) patients, this study aims to
      analyze the effects of these factors on the pathogenesis of IBD. According to
      illness status, selected patients were divided into Crohn?s disease (CD) group
      (28 patients), ulcerative colitis (UC) group (74 patients) and normal control
      group (36 patients); enzymelinked immunosorbent assay (ELISA) was used to detect
      IL-17A, IL-10 and IFN-gamma levels in serum; immunohistochemical assay was used
      to detect local IL-17A expression in the colonic mucosa of each group. Clinical
      results showed that IL-17A content of the UC group and CD group was significantly
      higher than that of the normal control group (p less than 0.05); IL-17A content
      of the CD group was higher than that of the UC group (p>0.05). The UC group had
      the highest IL-10 content, and the difference between the UC group and other two
      groups had statistical significance (p less than 0.05); the difference of IL-10
      content between UC group and normal control group had no statistical significance
      (p>0.05). There was no significant difference of IFN-gamma level between the CD
      group and the UC group and normal control group (p>0.05), and no significant
      difference of IFN-gamma level was shown between the CD group and the UC group
      (p>0.05). Both the CD and UC groups showed IL-17A positive staining in cytoplasm
      of lymphocyte, however no positive staining was found in any layer of intestinal
      mucosa of the normal control group. IL-17A was locally expressed in the colon of
      IBD patients in remission; furthermore, it also had high expression in serum;
      thus, there still existed high expression of pro-inflammatory factor, which might
      be related to relapse of IBD. Therefore, prevention of IL-17A may become a
      feasible therapy for IBD in the future. 

PMID- 27049091
TI  - Comparison of laparoscopy and open surgery in treating severe acute pancreatitis
      and its relative aftercare.
AB  - This study was designed to determine the effects and compare laparoscopic
      intervention and open surgery in treating severe acute pancreatitis (SAP) and its
      relative aftercare, to improve the overall treatment of SAP. Ninety patients with
      SAP were enrolled from the 2nd Affiliated Hospital of Harbin Medical University
      from 2008 to 2014 and divided into a laparoscopic intervention group (25 cases)
      and an open surgery group (65 cases). Patients were asked for clinical symptoms,
      general hospital information, laboratory inspection, imageological examination,
      local and systemic complications, treatment and outcome. SAP patients? relevant
      clinical indicators were compared between the two groups before and after the
      operation. Results revealed that there was no statistical significance in lesion
      range and main scoring indexes for reflecting the severity of the disease. For
      both groups statistical significance was found in blood loss (285.3+/-79.8 mL vs
      362+/-91.6 mL), intensive care unit (ICU) monitoring time (9.04+/-6.35 d vs
      12.48+/-8.34 d) and service time of breathing machine (9.47+/-6.24 d vs 12.98+/
      8.25 d), and the laparoscopic operation group was superior to the open surgery
      group (p < 0.05). Besides, the laparoscopic operation group was also superior to
      the open surgery group in demand for main analgesics one week after the
      operation, as well as for recovery rate and incidence of complications (p <
      0.05). Thus, it can be concluded that patients undergoing laparoscopic
      intervention are less likely to develop pulmonary infection and more likely to be
      cured in comparison with patients who receive open surgery. In addition,
      laparoscopic intervention results in less damage, lighter pain and fewer
      complications compared with open surgery.

PMID- 27049092
TI  - Expression of CD4+CD25+ regulatory T cells and Foxp3 in peripheral blood of
      patients with gastric carcinoma.
AB  - The aim of this research was to study the clinical significance and expression of
      CD4+CD25+ regulatory T cells (Tregs) and p3Forkhead transcription factor-3
      (Foxp3) in peripheral blood of patients with gastric carcinoma (GC) and to
      investigate the effects in the occurrence and development process of GC, to
      further comprehend their clinical values and provide a theoretical basis for the
      early diagnosis and immunotherapy of GC. The expression levels of
      CD4+CD25+Foxp3+Tregs in GC patients, at TNM staging, differentiated degree,
      lymphatic metastasis, cancer sites and cancer diameter of GC, were analyzed
      within the groups. The comparison of the expression levels of
      CD4+CD25+Foxp3+Tregs in peripheral blood between the GC group and the healthy
      control group showed a statistically significant difference. At TNM staging
      within the groups, pairwise comparisons of the expression levels of
      CD4+CD25+Foxp3+Tregs indicated that differences among the stage I+II group, stage
      III group and stage IV group were statistically significant. The expression
      levels of CD4+CD25+Foxp3+Tregs are closely relative to the occurrence and
      development of GC, providing theoretical bases and evidence for the early
      diagnosis, prognosis evaluation and immunotherapy of GC. 

PMID- 27049093
TI  - Clinical effect of intravitreous injection of triamcinolone acetonide in treating
      cystoid macular edema.
AB  - Cystoid macular edema (CME), a commonly seen sign for multiple fundus diseases,
      is able to induce visual deterioration. The incidence rate of CME is constantly
      increasing; however, the existing clinical treatments cannot achieve satisfactory
      curative effects. To explore the curative effect of intravitreous injection of
      triamcinolone acetonide (TA) in treating CME, this study carried out a clinical
      test on 39 patients (42 eyes) from The First Affiliated Hospital of Zhengzhou
      University who developed CME induced by central retinal vein occlusion (CRVO).
      All 42 eyes received intravitreous injection of 40 mg/ml TA (0.1 ml) and then
      were followed up for 11-23.5 months. Eyes were examined by slit-lamp microscope,
      fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) and
      best corrected visual acuity (BCVA), and intraocular pressure (IOP) of those eyes
      were detected before and after treatment. Average vision of eyes was 0.1 before
      treatment, and the vision improved in one month (vision >= 0.2: 100%; vision >=
      0.5: 42.9%) and three months (vision >= 0.2: 64.3%; vision >= 0.5: 21.4%) after
      treatment; but as time went on, the vision of some patients declined; at the last
      follow-up, patients with vision >= 0.2 accounted for 28.6% and those with vision
      >=0.5 accounted for 7.1%; compared to before treatment, 71.4% patients had
      improved vision and the remaining 28.6% had declined vision. Some patients were
      observed with high IOP during treatment, and 7 eyes were found with secondary
      cataract in posterior capsule of lens at the last follow-up. Intravitreous
      injection of triamcinolone acetonide proved to have significant short-term
      curative effect on CEM which is non-sensitive to conventional therapies, but it
      is likely to induce high IPO and posterior capsular opacification. 

PMID- 27049094
TI  - Ultrasound diagnosis in gynecological acute abdomen.
AB  - As ultrasound diagnosis is applied more frequently in gynecological acute
      abdomen, we carried out this study to discuss the diagnosis of endometriosis with
      ultrasound imaging and analyze the efficacy of microRNA used for diagnosing
      endometriosis and evaluating prognosis by comparing differentially expressed
      microRNA in subjects with or without endometriosis. Ultrasound examination
      results and clinical pathological examination results of 60 cases of
      gynecological acute abdomen were compared. Blood samples were collected from
      patients with endometriosis. Of 60 cases, 38 cases recurred in 20 months after
      surgery and the remaining 22 cases had no recurrence in the 30-month follow-up.
      Additionally, blood was collected from 40 patients without endometriosis as
      control. Then total RNA was extracted from these blood samples to determine the
      difference of expression of microRNA (miR-17-5p, miR-20a, miR-199a and miR-141).
      Compared to healthy subjects, the endometriosis patients showed significantly
      increased expression of miR-199a, but the expression of miR-17-5p, miR-20a and
      miR-141 had an obvious decrease; the differences were statistically significant
      (p less than 0.01). For recurred cases, miR-199 showed a remarkably high
      expression and miR-17-5p and miR-20a expressed significantly low. 

PMID- 27049095
TI  - Correlation between molybdenum target mammography signs and pathological
      prognostic factors of breast cancer.
AB  - This study explores the correlation between molybdenum target (mo-target)
      mammography signs and pathological prognostic factors of breast cancer. We
      selected 320 breast cancer patients who were treated between January 2014 and
      January 2016; using single-factor and multiple-factor logistic regression method,
      we made correlation analysis on their clinical features, pathological features
      and mo-target mammography signs. Among mo-target mammography signs, lumps
      accompanied with calcification and blurry edge were associated with high
      histologic grades; lumps accompanied with calcification and clear edge were
      associated with Ki-67 positive; compared with the patients who had lumps with non
      stellate edges, positive rates of estrogen receptor (ER) and progesterone
      receptor (PR) were significantly higher for the patients who had lumps with
      stellate edges (p < 0.01), while positive rate of human epidermal growth factor
      receptor-2 (HER-2) and tumor proliferative activity were significantly lower (p <
      0.05, p < 0.01). According to the study, we can conclude that mo-target
      mammography signs mainly include lumps and calcification. Mo-target mammography
      can improve the accuracy of diagnosis and reduce misdiagnosis or missed
      diagnosis. Part of mo-target mammography signs are associated with clinical
      pathology prognostic factors; by grasping the relation, breast cancer patient
      conditions are expected to be relieved.

PMID- 27049096
TI  - Early enteral and parenteral nutrition on immune functions of neurocritically ill
      patients.
AB  - This study was designed to investigate the influence of early enteral and
      parenteral nutrition on immune functions of neurocritically ill patients.
      Patients who were admitted to the neurological intensive care unit (ICU) of The
      Second Affiliated Hospital of Zhengzhou University between May 2014 and January
      2016 were selected. They had been hospitalized for more than one week and
      received enteral nutrition (EN) via nasogastric tube, with a gross energy of 25
      kcal/(Kg ? d). Patients were divided into EN group, EN + early PN (EPN) group and
      EN + supplemental PN (SPN) group according to the time of PN support. Differences
      in patients? general information and changes in serum protein and immune indexes
      were compared between the three groups. On admission, patients? Glasgow coma
      scale (GCS), age, immune functions and protein indexes had no obvious differences
      between the three groups. After nutritional support, serum protein level reduced
      in the EN group while prealbumin (PALB) and retinol binding protein (RBP)
      increased in the EN + EPN group and EN + SPN group after one week of admission to
      hospital, and the differences were statistically significant (p less than 0.05).
      Total protein (TP), albumin (ALB), PALB and transferrin (TRF) increased
      significantly in the EN + EPN group and EN + SPN group compared with the EN group
      (p < 0.05); before and after treatment, an increase was found in ALB in the EN +
      EPN group in comparison with EN + SPN group, with a notable difference (p <
      0.05); C3, C4, immunoglobulin M (IgM) and immunoglobulin A (IgA) increased in the
      EN + SPN group after nutritional support compared with before treatment, and the
      difference was statistically significant (p < 0.05). Moreover, immunoglobulin G
      (IgG) and IgA in the EN + EPN group increased after nutritional support comparing
      to prior to nutritional support, and the difference was statistically significant
      (p < 0.05). After nutritional treatment, IgA and IgG increased markedly in the EN
      + EPN group, and there was a statistical significance between the groups (p <
      0.05); the EN + EPN group and EN + SPN group exceeded the EN group in total
      lymphocyte count (TLC), and the difference had a statistical significance (p less
      than 0.05). These results demonstrate that neurocritically ill patients achieving
      the target energy can avoid malnutrition and immunodeficiency; serum protein
      decrease can cause malnutrition after one week of EN support; and enteral and
      parenteral nutrition can improve nutritional and immune indicators of
      neurocritically ill patients in the acute phase. In addition, EPN is more likely
      to improve malnutrition and immune functions of critical patients than SPN.

PMID- 27049097
TI  - Changes of HMGB1 expression on angiogenesis of ovarian cancer and its mechanism.
AB  - This study was designed to investigate the changes of high-mobility group box-1
      (HMGB1) expression and its effects on regulating the angiogenesis of ovarian
      cancer. HMGB1 eukaryotic expression plasmid and artificially synthesized small
      interfering ribose nucleic acid (siRNA) were constructed to transfer SKOV3 cell,
      respectively. Western blot was adopted to investigate the changes of HMGB1,
      CXCL12 and vascular endothelial growth factor (VEGF) before and after the
      transfection and flow cytometry (FCM) was applied to detect SKOV3 apoptosis.
      Results revealed that the apoptosis rates of SKOV3 cell were 32.8+/-2.2%, 33.9+/
      1.9% and 11.7+/-1%, respectively, in the control group, no-load group and
      transfection group after 2-d cisplatin treatment (10 MUg/mL). The apoptosis rate
      in the transfection group was obviously lower than that in the control group and
      no-load group (p = 0.00) while no significant difference was found in the
      apoptosis rate in the other two groups (p = 0.75). Furthermore, the apoptosis
      rates of SKOV3 cell in the SKOV3 group, negative control group, SKOV3-ribose
      nucleic acid interfere (RNAi) group were 7.9+/-0.5%, 8.3+/-0.8% and 29.5+/-1.3%
      respectively. The apoptosis rate was notably higher in SKOV3-RNAi group than in
      the SKOV3 group and negative control group (p < 0.001) while no significant
      difference was found in the apoptosis rate in the other two groups (p = 0.89).
      Thus, it can be concluded that HMGB1 interference can reduce VEGF and CXCL12
      expression in ovarian cancer cells, but increase the apoptosis of ovarian cancer
      cells. Moreover, HMGB1 is highly expressed in cytoplasm and karyon.

PMID- 27049098
TI  - Correlation between genetic susceptibility of tuberculosis and macrophage
      migration inhibitory factor.
AB  - This paper aims to study the relationship between genetic susceptibility of
      tuberculosis and macrophage migration inhibitory factor (MIF) and provide
      theoretical basis and foundation for further studies on pathogenesis and
      treatment of tuberculosis. Enzyme Linked Immuno Sorbent Assay (ELISA) was applied
      to detect the difference of MIF protein expression level in peripheral serum of
      the test subjects, and analyze the difference of MIF protein expression levels of
      different genotypes and alleles at -794CATT locus and -173G/C locus. The results
      showed that MIF protein expression level in serum of patients in the tuberculosis
      group was higher than that of the healthy control group (p < 0.05). The MIF
      protein expression level of genotype (5/5+5/6+6/6) and (7/X+8/X) at -794CATT
      locus of the tuberculosis group was higher than that of the healthy control group
      (p < 0.05), and MIF protein expression level of genotype GG and (GC+CC) at 
      173G/C locus of the tuberculosis group was higher than that of the healthy
      control group (p < 0.05). Therefore, macrophage migration inhibitory factor is an
      important cell factor which plays a regulating role in the immune system, as it
      can inhibit macrophage migration and promote the gathering, infiltration and
      proliferation of macrophages at inflammatory sites. Furthermore, it can secrete
      some cell factors which play a central role in immunological regulation.

PMID- 27049099
TI  - Efficacy of traditional Chinese medicine for cooling blood and eliminating toxins
      and strengthening and purifying spleen in the treatment of refractory hepatitis
      C.
AB  - This study was designed to observe the comprehensive efficacy of traditional
      Chinese medicine (TCM) combined with interferon in the treatment of chronic
      hepatitis C (CHC), compare this combined therapy with interferon therapy alone
      and investigate its possible mechanism to provide a basis for the development of
      an integrated traditional Chinese and Western medicine for the treatment of CHC.
      According to patient contraindications for antiviral treatment, patients who were
      suitable for interferon therapy and willing to use TCM were enrolled as combined
      traditional Chinese and Western medicine group, and 21 CHC patients were selected
      as Western medicine control group; patients who had contraindications for
      antiviral treatment were included in the TCM group. The three groups of patients
      were all diagnosed with positive hepatitis C virus - ribose nucleic acid (HCV
      RNA). The treatment course lasted for one year and the patients were followed up
      for 12 months. Patients? demographic data, course of disease, chronic liver
      disease questionnaire (CLDQ), genetic typing, biochemical indexes, HCV-RNA and
      side effects were compared between the groups. The efficacy, incidence of side
      effects and improvement in quality of life were analyzed in each group. Results
      showed that the combination of TCM and interferon could protect liver, reduce
      side effects and also improve quality of life of the patients, while the
      antiviral activity of TCM alone was not obvious. 

PMID- 27049100
TI  - Ancillary therapy of intranasal T-LysYal(r) for patients with allergic, non
      allergic, and mixed rhinitis.
AB  - Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction. Non
      allergic rhinitis (NAR) is characterized by a non-IgE-mediated pathogenesis.
      Frequently, patients have the two disorders associated: such as mixed rhinitis
      (MR). Hyaluronic acid (HA) is a fundamental component of the human connective
      tissue. HA may exert anti-inflammatory and immune-modulating activities.
      Recently, an intranasal HA formulation was proposed: a supramolecular system
      containing lysine hyaluronate, thymine and sodium chloride (T-LysYal(r)). This
      randomized study investigated whether intranasal T-LysYal(r) (rinoLysYal(r),
      Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and
      nasal cytology in 89 patients (48 males and 41 females, mean age 36.3+/-7.1
      years) with AR, NAR, and MR. Patients were treated with intranasal T-LysYal(r) or
      isotonic saline solution as adjunctive therapy to nasal corticosteroid and oral
      antihistamine for 4 weeks. Patients were visited at baseline, after treatment and
      after 4-week follow-up. Intranasal T-LysYal(r) treatment significantly reduced
      the quote of patients with symptoms, endoscopic features, and inflammatory cells.
      In conclusion, the present study demonstrates that intranasal T-LysYal(r) is
      able, as ancillary therapy, to significantly improve patients with AR, NAR, and
      MR, and its effect is long lasting. 

PMID- 27049101
TI  - 8-isoprostane in exhaled breath condensate after experimental exposure to wood
      smoke in humans.
AB  - Wood smoke, a well-known indoor and outdoor air pollutant, may cause adverse
      health effects through oxidative stress. In this study 8-isoprostane, a biomarker
      of oxidative stress, was measured in exhaled breath condensate (EBC) and urine
      before and after experimental exposure to wood smoke. The results were compared
      with measurements of other biomarkers of oxidative stress and inflammation.
      Thirteen subjects were exposed first to clean air and then, after 1 week, to wood
      smoke in an exposure chamber during 4-hour sessions. Exhaled breath condensate,
      exhaled nitric oxide, blood and urine were sampled before and at various
      intervals after exposure to wood smoke and clean air. Exhaled breath condensate
      was examined for 8-isoprostane and malondialdehyde (MDA), while exhaled air was
      examined for nitric oxide, serum for Clara cell protein (CC16) and urine for 8
      isoprostane. 8-isoprostane in EBC did not increase after wood smoke exposure and
      its net change immediately after exposure was inversely correlated with net
      changes in MDA (r(s)= -0.57, p= 0.041) and serum CC16 (S-CC16) (r(p)= -0.64, p=
      0.020) immediately after the exposure. No correlation was found between 8
      isoprostane in urine and 8-isoprostane in EBC. In this study controlled wood
      smoke exposure in healthy subjects did not increase 8-isoprostane in EBC.

PMID- 27049102
TI  - Hypertonic saline monotherapy in children with perennial allergic rhinitis: a
      pilot study.
AB  - Perennial allergic rhinitis (PAR) is very common in children and has a relevant
      impact on their families. House dust mites (HDM) are the most relevant cause of
      PAR. The present pilot study aimed to evaluate whether hypertonic saline (3%)
      nasal spray as monotherapy is able to improve: nasal symptom severity and
      parental perception of rhinitis control, sleep, and school performance in HDM
      mono-sensitized children with PAR. Globally, 25 children (13 males and 12
      females; mean age 9.5+/-3.1 years) were treated for 3 weeks. They were visited at
      baseline, at the end of treatment, and after a 2-week follow-up. Hypertonic
      saline significantly reduced total symptom score, and improved the perception,
      according to their parents, of rhinitis control, sleep, and school performance.
      In conclusion, the present pilot study provided the first evidence that 3%
      hypertonic saline monotherapy was able to relieve nasal symptoms and parental
      perception of PAR impact as well as being safe and well tolerated. 

PMID- 27049103
TI  - Intranasal T-LysYal(r) as adjunctive therapy for patients after functional
      endoscopic sinus surgery.
AB  - Functional Endoscopic Sinus Surgery (FESS) is a common day surgery technique for
      upper airway disorders. Hyaluronic acid (HA) is a fundamental component of the
      human connective tissue. HA may exert reparative, anti-inflammatory and immune
      modulating activities. Recently, a new intranasal HA formulation has been
      proposed: a supramolecular system containing lysine hyaluronate, thymine and
      sodium chloride (T-LysYal(r)). This randomized study investigated whether
      intranasal T-LysYal(r) (RinoLysYal(r), Farmigea, Italy) was able to reduce
      symptom severity, endoscopic features, and nasal cytology in 83 patients (49
      males and 34 females mean age 45.4+/-6.2 years) treated with FESS. All patients
      were treated with isotonic saline solution for 4 weeks, and a sub-group (active
      group) was also treated with intranasal T-LysYal(r). Patients were visited at
      baseline, after treatment, and after 4-week follow-up. Intranasal T-LysYal(r)
      treatment significantly reduced the quote of patients with symptoms, endoscopic
      features, and inflammatory cells in comparison to isotonic solution. In
      conclusion, the present study demonstrates that intranasal T-LysYal(r) is able to
      significantly improve patients after FESS and its effect is long lasting. 

PMID- 27049104
TI  - Nasal nitric oxide in children with recurrent acute otitis media.
AB  - Recently, reduced Nasal nitric oxide (nNO) nNO levels have been reported in
      children with adenoidal hypertrophy predisposing to chronic nasosinusal
      inflammation. Given the strict anatomic and physiopathologic link between the
      nasopharyngeal and middle ear compartments, and considering the high prevalence
      of otitis prone children among those affected with chronic adenoiditis, we
      designed a study aimed to test any possible difference in nNO levels between non
      allergic children with and without recurrent acute otitis media (RAOM) associated
      with chronic adenoiditis. The study involved 54 children with RAOM (44.4% males;
      mean age= 7.5+/-3.5 years) and 51 children without RAOM (47.4% males; mean age=
      7.0+/-3.8 years). nNO levels were significantly reduced in children with RAOM
      compared to children without RAOM (676.9+/-250.7 ppb vs 831.8+/-320.4 ppb,
      respectively; p= 0.02). Our results could be related to reduced NO production by
      the ciliated paranasal, nasopharyngeal and middle ear epithelium and the impaired
      sinusal ostial and Eustachian tube patency due to chronic inflammation, and seem
      to confirm the involvement of NO pathway in recurrent upper airway infections
      related to impaired ciliated respiratory mucosa. 

PMID- 27049105
TI  - Accelerated bone turnover identifies hemiplegic patients at higher risk of
      demineralization.
AB  - Immobilization osteoporosis represents a severe complication in hemiplegic
      patients (HPs), causing fragility fractures, which may occur during
      rehabilitation reducing functional recovery and survival. The aim of the study
      was to investigate determinants of bone loss, independent from length of
      immobilization, which may be useful in early identification of HPs at higher risk
      of demineralization. Forty-eight HPs of both sexes underwent anthropometric
      measurements, evaluation of scores of spasticity and of lower limb motory
      capacity. Laboratory tests were performed. On serum: calcium; phosphorus;
      creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Delta4-androstenedione;
      DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and
      calcium/creatinine ratio. Two bone turnover markers were measured: serum
      osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was
      determined at both femoral necks, defining a percentage difference in bone loss
      between paretic and non-paretic limb, thus controlling for the complex cofactors
      involved. Only bone turnover markers significantly and directly correlated with
      the entity of demineralization, controlling for age, sex and length of
      immobilization in the multivariate analysis (BGP coefficient estimate=0.008;
      SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and
      DPD are not dependent on anthropometric and endocrine-metabolic parameters,
      disability patterns and duration of immobilization, thus represent independent
      determinants of the degree of demineralization. A cutoff was defined for BGP and
      DPD above which subjects show significantly greater risk of demineralization. The
      immobilization event generates more severe bone loss when it occurs in subjects
      with higher bone turnover. BGP and DPD measurements may be of primary importance
      for early identification of HPs at risk, with relevant preventive implications.

PMID- 27049106
TI  - Epidemiology of diabetes mellitus in the fragility fracture population of a
      region of Southern Italy.
AB  - Increased risk of osteoporosis and its clinical significance in patients with
      diabetes is controversial. This study aims to increase the data which are
      available regarding the prevalence of diabetes mellitus in patients affected by
      fragility fracture in Italy. We retrospectively studied Hospital Discharge Data
      (HDD) in the Apulian database for the period 2006?2010 to identify a fragility
      fracture diagnosis in males over 65 years of age and in females over 50. The
      database was then checked for drug prescriptions to identify those persons who
      had taken at least one osteoporosis drug. Within this latter group, thanks to
      hospital admission and prescription records, the subjects affected with diabetes
      mellitus were identified. Between 2006 and 2010 in Apulia 177,639 patients were
      hospitalized and diagnosed as having fragility fracture. The greatest number of
      those fragility fractures were found to be in the 70 to 79 age range (64,917
      total; females 56,994, males 7,923). The prevalence of diabetes subjects in
      Apulia in this period was estimated at 6.5%. In the same region and period 21.1%
      of subjects affected by diabetes experienced a fragility fracture; in particular,
      this number was 27% for males and for 20.5% females. This is the first study
      providing data on the prevalence of fragility fractures and diabetes in the
      Apulian population. The data confirm that diabetes is a risk factor which
      influences bone density and risk of fractures and therefore the need of
      osteoporosis screening and treatment in diabetic patients. 

PMID- 27049107
TI  - Sodium hyaluronate improves quality of life and nasal endoscopy features in
      preschool children with upper respiratory tract infections.
AB  - The aim of this prospective, randomised study was to evaluate the effects of
      nasal douches with sodium hyaluronate on clinical and endoscopic variables, on
      parental perception of their child?s health-related quality of life (HR-QoL), and
      on parental workdays lost in preschool recurrent upper respiratory tract
      infections (URTIs). Children aged 2-6 years with recurrent or persistent URTIs
      underwent at baseline the evaluation of upper respiratory tract symptoms in the
      previous two weeks, and nasal endoscopy. Parents of enrolled children were
      assessed for self-perception of their children?s HR-QoL using a standardised
      questionnaire. The same variables were reassessed after a 2-week treatment with
      either 9 mg sodium hyaluronate plus saline solution or saline alone by nasal
      douches. Forty of the 48 children enrolled completed the study (22 assigned to
      the combined treatment). Compared to baseline, the combined treatment resulted in
      a significant reduction of the prevalence of children with missed daycare days
      (45% vs 14%, p=0.04) and of parents with workdays lost (36% vs 5%, p=0.02), and
      in a significant improvement of HR-QoL score (3.7 vs 2.8, p=0.004). At endoscopy,
      the secretion and mucosal oedema score significantly improved after the combined
      treatment (6 vs 2, p < 0.001), and there was a trend towards a reduction of the
      adenoid hypertrophy score (p=0.06). No clinical, HR-QOL or endoscopy changes were
      found in the saline group. In preschool children with recurrent or persistent
      URTIs, sodium hyaluronate by nasal douche significantly improves endoscopic
      features. Additional benefits include the children?s HR-QoL and daycare
      attendance, and parental work.

PMID- 27049108
TI  - Study of oral cavity lesions by infrared spectroscopy.
AB  - Fourier transform infrared (FTIR) microspectroscopy is considered a useful tool
      in the biomedical field, for analysing in situ and at cellular level, very small
      areas of tissues and cells, with minimal sample preparation and without the use
      of stains or probes. This spectroscopic technique has been successfully applied
      to analyse biological samples from patients affected by tumoral pathologies, with
      particular attention to oral cavity lesions. In this study, we describe the
      application of FTIR microspectroscopy to characterize and discriminate the most
      recurrent benign and malignant diseases of oral cavity compartment. Infrared maps
      were acquired on tissues affected by the following pathologies: squamous cell
      carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma,
      squamous dysplasia, keratocystic odontogenic tumor, radicular cyst, residual
      cyst, unicystic ameloblastoma, and ameloblastic fibroma, together with healthy
      tissue samples (used as control group). The epithelial and connective components
      of all samples were distinguished and submitted to multivariate analysis. The
      results were in agreement with histological suggestions. 

PMID- 27049110
TI  - The apparent charge of nanoparticles trapped at a water interface.
AB  - Charged spherical nanoparticles trapped at the interface between water and air or
      water and oil exhibit repulsive electrostatic forces that contain a long-ranged
      dipolar and a short-ranged exponentially decaying component. The former are
      induced by the unscreened electrostatic field through the non-polar low
      permittivity medium, and the latter result from the overlap of the diffuse ion
      clouds that form in the aqueous phase close to the nanoparticles. The magnitude
      of the long-ranged dipolar interaction is largely determined by the residual
      charges that remain attached to the air- (or oil-) exposed region of the
      nanoparticle. In the present work we address the question to what extent the
      charges on the water-immersed part of the nanoparticle provide an additional
      contribution to the dipolar interaction. To this end, we model the electrostatic
      properties of a spherical particle - a nanoparticle or a colloid - that
      partitions equatorially to the air-water interface, thereby employing nonlinear
      Poisson-Boltzmann theory in the aqueous solution and accounting for the
      propagation of the electric field through the interior of the particle. We
      demonstrate that the apparent charge density on the air-exposed region of the
      particle, which determines the dipole potential, is influenced by the
      electrostatic properties in the aqueous solution. We also show that this
      electrostatic coupling through the particle can be reproduced qualitatively by a
      simple analytic planar capacitor model. Our results help to rationalize the
      experimentally observed weak but non-vanishing salt dependence of the forces that
      stabilize ordered two-dimensional arrays of interface-trapped nanoparticles or
      colloids.

PMID- 27049109
TI  - PEP-1-GSTpi protein enhanced hippocampal neuronal cell survival after oxidative
      damage.
AB  - Reactive oxygen species generated under oxidative stress are involved in neuronal
      diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of
      the GST family and is known to play important roles in cell survival. We
      investigated the effect of GSTpi against oxidative stress-induced hippocampal HT
      22 cell death, and its effects in an animal model of ischemic injury, using a
      cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells
      and significantly protected against H2O2-treated cell death by reducing the
      intracellular toxicity and regulating the signal pathways, including MAPK, Akt,
      Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and
      markedly protected against neuronal cell death in an ischemic injury animal
      model. These results indicate that PEP-1-GSTpi acts as a regulator or an
      antioxidant to protect against oxidative stressinduced cell death. Our study
      suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the
      treatment of ischemia and a variety of oxidative stress-related neuronal
      diseases. [BMB Reports 2016; 49(7): 382-387]. 

PMID- 27049111
TI  - Sericin Composition in the Silk of Antheraea yamamai.
AB  - The silks produced by caterpillars consist of fibroin proteins that form two core
      filaments, and sericin proteins that seal filaments into a fiber and conglutinate
      fibers in the cocoon. Sericin genes are well-known in Bombyx mori (Bombycidae)
      but have received little attention in other insects. This paper shows that
      Antheraea yamamai (Saturniidae) contains five sericin genes very different from
      the three sericin genes of B. mori. In spite of differences, all known sericins
      are characterized by short exons 1 and 2 (out of 3-12 exons), expression in the
      middle silk gland section, presence of repeats with high contents of Ser and
      charged amino acid residues, and secretion as a sticky silk component soluble in
      hot water. The B. mori sericins represent tentative phylogenetic lineages (I)
      BmSer1 and orthologs in Saturniidae, (II) BmSer2, and (III) BmSer3 and related
      sericins of Saturniidae and of the pyralid Galleria mellonella. The lineage (IV)
      seems to be limited to Saturniidae. Concerted evolution of the sericin genes was
      apparently associated with gene amplifications as well as gene loses. Differences
      in the silk fiber morphology indicate that the cocktail of sericins linking the
      filaments and coating the fiber is modified during spinning. Silks are composite
      biomaterials of conserved function in spite of great diversity of their
      composition.

PMID- 27049112
TI  - Comparison of cranial sex determination by discriminant analysis and logistic
      regression.
AB  - SUMMARY: Various methods have been proposed for estimating dimorphism. The
      objective of this study was to compare sex determination results from cranial
      measurements using discriminant analysis or logistic regression. The study sample
      comprised 130 individuals (70 males) of known sex, age, and cause of death from
      San Jose cemetery in Granada (Spain). Measurements of 19 neurocranial dimensions
      and 11 splanchnocranial dimensions were subjected to discriminant analysis and
      logistic regression, and the percentages of correct classification were compared
      between the sex functions obtained with each method. The discriminant capacity of
      the selected variables was evaluated with a cross-validation procedure. The
      percentage accuracy with discriminant analysis was 78.2% for the neurocranium
      (82.4% in females and 74.6% in males) and 73.7% for the splanchnocranium (79.6%
      in females and 68.8% in males). These percentages were higher with logistic
      regression analysis: 85.7% for the neurocranium (in both sexes) and 94.1% for the
      splanchnocranium (100% in females and 91.7% in males).

PMID- 27049113
TI  - Odontometric sex estimation in humans using measurements on permanent canines. A
      comparison of an early Neolithic and an early medieval assemblage from Germany.
AB  - SUMMARY: This study analyzed whether cervical canine dimensions measured at the
      enamel-cement junction can provide a basis for sex estimation in human skeletal
      remains and whether discriminant functions developed for one assemblage can be
      successfully applied also to others. Cervical canine dimensions were recorded for
      an Early Neolithic (Linear Pottery Culture) and an early medieval skeletal
      assemblage from Germany. Only individuals in whom sex estimation based on
      standard diagnostic criteria could be performed with a high degree of certainty
      were included. Sexual dimorphism in cervical canine dimensions was higher in the
      early medieval assemblage. Values in females of the Early Neolithic assemblage
      exceeded those of the early medieval assemblage, while there were no significant
      differences in males. Discriminant analysis led to a maximum correct
      classification of sex (cross validation results) of 94.0% in the early medieval
      and of 79.2% in the Early Neolithic assemblage. Applying the discriminant
      functions developed on one assemblage to the other led to poor classification
      results. Cervical canine dimensions are highly correlated with sexually dimorphic
      skeletal traits and may provide a good basis for sexing archaeological
      individuals. It is suggested that due to population differences in canine
      dimensions, either assemblage specific discriminant functions should be developed
      or the applicability of existing formulae obtained on other assemblages to the
      assemblage under study should be carefully checked.

PMID- 27049114
TI  - Comparison Between a Self-Administered and Supervised Version of a Web-Based
      Cognitive Test Battery: Results From the NutriNet-Sante Cohort Study.
AB  - BACKGROUND: Dementia is a major public health problem, and repeated cognitive
      data from large epidemiological studies could help to develop efficient measures
      of early prevention. Data collection by self-administered online tools could
      drastically reduce the logistical and financial burden of such large-scale
      investigations. In this context, it is important to obtain data concerning the
      comparability of such new online tools with traditional, supervised modes of
      cognitive assessment. OBJECTIVE: Our objective was to compare self-administration
      of the Web-based NutriNet-Sante cognitive test battery (NutriCog) with
      administration by a neuropsychologist. METHODS: The test battery included four
      tests, measuring, among others aspects, psychomotor speed, attention, executive
      function, episodic memory, working memory, and associative memory. Both versions
      of the cognitive battery were completed by 189 volunteers (either self
      administered version first, n=99, or supervised version first, n=90). Subjects
      also completed a satisfaction questionnaire. Concordance was assessed by Spearman
      correlation. RESULTS: Agreement between both versions varied according to the
      investigated cognitive task and outcome variable. Spearman correlations ranged
      between .42 and .73. Moreover, a majority of participants responded that they
      "absolutely" or "rather" agreed that the duration of the self-administered
      battery was acceptable (184/185, 99.5%), that the tasks were amusing (162/185,
      87.6%), that the instructions were sufficiently detailed (168/185; 90.8%) and
      understandable (164/185, 88.7%), and that they had overall enjoyed the test
      battery (182/185, 98.4%). CONCLUSIONS: The self-administered version of the Web
      based NutriCog cognitive test battery provided similar information as the
      supervised version. Thus, integrating repeated cognitive evaluations into large
      cohorts via the implementation of self-administered online versions of
      traditional test batteries appears to be feasible.

PMID- 27049115
TI  - Hepatoprotective effect of isoquercitrin against acetaminophen-induced liver
      injury.
AB  - AIMS: Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Isoquercitrin
      exhibited potential hepatoprotective effect in our previous study. The present
      investigation aimed to evaluate the effect of isoquercitrin against APAP induced
      liver injury and to explore its possible mechanism. MAIN METHODS: Mice were
      treated intragastrically with isoquercitrin (10, 20, or 50mg/kg) for 3days before
      APAP (300mg/kg) injection. After 24h from APAP treatment, the levels of serum
      aminotransferase, hepatic oxidative stress and nitrosative stress biomarkers were
      determined by commercial kits or western bolt. Activities of UDP
      glucuronosyltransferases (UGTs), sulfotransferases (SULTs) and cytochrome 2E1
      (CYP2E1) were evaluated using ELISA methods and standard biochemical procedures.
      Subsequently, the protein and mRNA levels of inflammatory factors including TNF
      alpha, IL-1beta, IL-6 and iNOS were determined using ELISA methods, western blot
      or real-time PCR. The effect of isoquercitrin on APAP activated NFkappaB/MAPK
      pathway was assessed by western bolt. KEY FINDINGS: Isoquercitrin pretreatments
      markedly attenuated APAP induced hepatic oxidative stress, nitrosative stress and
      centrilobular necrosis. In addition to potent antioxidant activity, isoquercitrin
      was able to regulate the activities of SULTs and CYP2E1, therefore promoted APAP
      hepatic detoxification. The anti-inflammatory activity of isoquercitrin which
      involved in the amelioration of iNOS, TNF-alpha, IL-1beta and IL-6 production via
      the blockade of NF-kappaB and MAPK pathways also responsible for its
      hepatoprotective effect. SIGNIFICANCE: Our data evidenced that isoquercitrin
      protected liver from APAP induced injury though inhibition of oxidative stress,
      nitrosative stress and inflammation, as well as regulation of APAP metabolism,
      suggesting that isoquercitrin could be a potential hepatoprotective agent.

PMID- 27049116
TI  - Mitochondrial dysfunction in H9c2 cells during ischemia and amelioration with
      Tribulus terrestris L.
AB  - AIMS: The present study investigates the protective effect of partially
      characterized Tribulus terrestris L. fruit methanol extract against mitochondrial
      dysfunction in cell based (H9c2) myocardial ischemia model. MAIN METHODS: To
      induce ischemia, the cells were maintained in an ischemic buffer (composition in
      mM -137 NaCl, 12 KCl, 0.5 MgCl2, 0.9 CaCl2, 20 HEPES, 20 2-deoxy-d-glucose, pH
      6.2) at 37 degrees C with 0.1% O2, 5% CO2, and 95% N2 in a hypoxia incubator for
      1h. Cells were pretreated with various concentrations of T. terrestris L. fruit
      methanol extract (10 and 25MUg/ml) and Cyclosporin A (1MUM) for 24h prior to the
      induction of ischemia. KEY FINDINGS: Different parameters like lactate
      dehydrogenase release, total antioxidant capacity, glutathione content and
      antioxidant enzymes were investigated. Studies were conducted on mitochondria by
      analyzing alterations in mitochondrial membrane potential, integrity, and
      dynamics (fission and fusion proteins - Mfn1, Mfn2, OPA1, Drp1 and Fis1). Various
      biochemical processes in mitochondria like activity of electron transport chain
      (ETC) complexes, oxygen consumption and ATP production was measured. Ischemia for
      1h caused a significant (p<=0.05) increase in LDH leakage, decrease in
      antioxidant activity and caused mitochondrial dysfunction. T. terrestris L. fruit
      methanol extract pretreatment was found effective in safeguarding mitochondria
      via its antioxidant potential, mediated through various bioactives. HPLC of T.
      terrestris L. fruit methanol extract revealed the presence of ferulic acid,
      phloridzin and diosgenin. SIGNIFICANCE: T. terrestris L. fruit ameliorate
      ischemic insult in H9c2 cells by safeguarding mitochondrial function. This
      validates the use of T. terrestris L. against heart disorders.

PMID- 27049117
TI  - Electrical microstimulation of the nucleus incertus induces forward locomotion
      and rotation in rats.
AB  - Locomotion is essential for goal-oriented behavior. Theta frequency oscillations
      in the hippocampus have been associated with behavioral activation and initiation
      of movement. Recently, the nucleus incertus, a brainstem nucleus with widespread
      cortical and subcortical projections, has been reported to modulate the septo
      hippocampal axis triggering theta activity in the hippocampus. This suggests that
      activation of the nucleus incertus would induce movement. In this study, we
      investigated the effects of electrical microstimulation of the nucleus incertus
      on locomotion in conscious rats. Rats chronically implanted with microelectrodes
      targeting the nucleus incertus were electrically stimulated while their behavior
      was tracked. High frequency electrical microstimulation of the nucleus incertus
      was sufficient to induce forward locomotion and rotation. The latencies of evoked
      locomotion were consistent with a role of the nucleus incertus in modulating
      premotor areas, possibly the septo-hippocampal axis. Electrical microstimulation
      of the nucleus incertus increased velocity, mobility and rotations during
      stimulation and post-stimulation. These results suggest that the nucleus incertus
      plays a role in behavioral activation and locomotion.

PMID- 27049118
TI  - 14-Deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic
      reticulum stress-mediated autophagy in T-47D breast carcinoma cells.
AB  - 14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated
      from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits
      a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the
      mechanistic toxicology properties of 14-DDA in T-47D cells were further
      investigated. 14-DDA is found to induce the formation of endoplasmic reticulum
      (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the
      breast carcinoma cells. It stimulated an increase in cytosolic calcium
      concentration and caused a collapse in mitochondrial membrane potential in these
      cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress
      pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation
      of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress
      and autophagy is dependent on this transcription factor. Collectively, it is
      possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER
      stress-mediated autophagy in T-47D cells.

PMID- 27049119
TI  - Proteasomes generate spliced epitopes by two different mechanisms and as
      efficiently as non-spliced epitopes.
AB  - Proteasome-catalyzed peptide splicing represents an additional catalytic activity
      of proteasomes contributing to the pool of MHC-class I-presented epitopes. We
      here biochemically and functionally characterized a new melanoma gp100 derived
      spliced epitope. We demonstrate that the gp100(mel)47-52/40-42 antigenic peptide
      is generated in vitro and in cellulo by a not yet described proteasomal
      condensation reaction. gp100(mel)47-52/40-42 generation is enhanced in the
      presence of the beta5i/LMP7 proteasome-subunit and elicits a peptide-specific
      CD8(+) T cell response. Importantly, we demonstrate that different gp100(mel)
      derived spliced epitopes are generated and presented to CD8(+) T cells with
      efficacies comparable to non-spliced canonical tumor epitopes and that gp100(mel)
      derived spliced epitopes trigger activation of CD8(+) T cells found in peripheral
      blood of half of the melanoma patients tested. Our data suggest that both
      transpeptidation and condensation reactions contribute to the frequent generation
      of spliced epitopes also in vivo and that their immune relevance may be
      comparable to non-spliced epitopes. 

PMID- 27049121
TI  - Accumulation of copper in the kidney of pigs fed high dietary zinc is due to
      metallothionein expression with minor effects on genes involved in copper
      metabolism.
AB  - A study was conducted to determine the effect of high dietary zinc (Zn) oxide on
      trace element accumulation in various organs with special emphasis on the kidney.
      A total of 40 weaned piglets were allocated into two groups with 16 and 24
      piglets each receiving a diet containing normal (NZn; 100mg Zn/kg) or high (HZn;
      2,100mg Zn/kg) Zn concentration, respectively. After two weeks, eight piglets
      from each treatment were killed and organ samples were taken. Eight piglets from
      the remaining 16 pigs fed HZn diets were changed to NZn diets (CZn). All
      remaining piglets were killed after another two weeks for organ sampling. Trace
      element concentration was determined in the jejunum, liver, kidney, pancreas,
      bone (metacarpal IV), spleen, lung, thymus, tonsils and lymph nodes of jejunum,
      ileum and colon. Kidney mRNA expression of Zn transporter ZnT1 and ZIP4, genes
      involved in Cu metabolism (Ctr1, Atox1, SOD1, ATP7A, CCS, CP) and divalent metal
      ion transport (DMT1) and binding (MT-1a, MT-2b, MT-3) were determined. The Zn
      concentration in jejunum, liver, pancreas tissue and metacarpal IV was higher
      (P<0.05) in HZn group compared with NZn and CZn groups. Trace element
      concentration in organs of CZn pigs was similar to those fed NZn diets. Zn
      concentration in muscle, lung and lymphatic organs as thymus, tonsils, spleen and
      lymph nodes of jejunum, ileum and colon did not differ between the groups. Zn and
      Cu were positively correlated (R=0.67; P<0.05) in the kidney. No significant
      differences for Cu chaperones, Cu transporters and Cu-dependent factors were
      determined despite decreased expression of Atox1 after two weeks and increased
      Ctr1 expression over time in the HZn group. Expression of MT-1a, MT-2b and MT-3
      were significantly higher in HZn fed pigs with most pronounced effects for MT-1a
      > MT-2b > MT-3. Gene expression of MTs in pigs fed CZn diets did not differ from
      pigs fed NZn diets. The data suggest that high dietary Zn feeding in pigs leads
      to Cu co-accumulation in the kidney of pigs with minor effect on genes relevant
      for Cu metabolism. In addition, the organ Zn and Cu accumulation is reversible
      after two weeks of withdrawal of high dietary Zn. 

PMID- 27049120
TI  - Can the vaccine adverse event reporting system be used to increase vaccine
      acceptance and trust?
AB  - Vaccine refusal has an impact on public health, and the human pappillomavirus
      (HPV) vaccine is particularly underutilized. Research suggests that it may be
      difficult to change vaccine-related attitudes, and there is currently no good
      evidence to recommend any particular intervention strategy. One reason for
      vaccine hesitancy is lack of trust that vaccine harms are adequately documented
      and reported, yet few communication strategies have explicitly attempted to
      improve this trust. This study tested the possibility that data from the vaccine
      adverse event reporting system (VAERS) can be used to increase trust that vaccine
      harms are adequately researched and that potential harms are disclosed to the
      public, and thereby improve perceptions of vaccines. In the study, participants
      were randomly assigned to one of three communication interventions. All
      participants read the Centers for Disease Control (CDC) vaccine information
      statement (VIS) for the HPV vaccine. Two other groups were exposed to additional
      information about VAERS, either summary data or full detailed reports of serious
      adverse events from 2013. Results showed that the CDC's VIS alone significantly
      increased perceptions of vaccine benefits and decreased perceived risks.
      Participants who were also educated about VAERS and given summary data about the
      serious adverse events displayed more trust in the CDC and greater HPV vaccine
      acceptance relative to the VIS alone. However, exposure to the detailed VAERS
      reports significantly reduced trust in the CDC and vaccine acceptance. Hence,
      general information about the VAERS data slightly increased trust in the CDC and
      improved vaccine acceptance, but the specific VAERS reports negatively influenced
      both trust and acceptance. Implications for communicating about vaccines are
      discussed.

PMID- 27049122
TI  - Dietary supplementation of green synthesized manganese-oxide nanoparticles and
      its effect on growth performance, muscle composition and digestive enzyme
      activities of the giant freshwater prawn Macrobrachium rosenbergii.
AB  - The green synthesized Mn3O4 nanoparticles (manganese-oxide nanoparticles) using
      Ananas comosus (L.) peel extract was characterized by various techniques. HR-SEM
      photograph showed that manganese-oxide nanoparticles (Mn-oxide NPs) were
      spherical in shape, with an average size of 40-50 nm. The Zeta potential revealed
      the surface charge of Mn-oxide NPs to be negative. Further, the Mn-oxide NPs were
      dietary supplemented for freshwater prawn Macrobrachium rosenbergii. The
      experimental basal diets were supplemented with Mn-oxide NPs at the rates of 0
      (control), 3.0, 6.0, 9.0, 12, 15 and 18 mg/kg dry feed weight. The as
      supplemented Mn-oxide NPs were fed in M. rosenbergii for a period of 90 days. The
      experimental study demonstrated that prawns fed with diet supplemented with 3-18
      mg Mn-oxide NPs/kg shows enhanced (P<0.05) growth performance, including final
      weight and weight gain (WG). Significant differences (P<0.05) in feed conversion
      ratio (FCR) were observed in prawn fed with different diets. Additionally, prawns
      fed with 3.0-18 mg/kg Mn-oxide NPs supplemented diets achieved significant
      (P<0.05) improvement in growth performance, digestive enzyme activities and
      muscle biochemical compositions, while, the prawns fed with 16 mg/kg of Mn-oxide
      NPs showed enhanced performance. Prawns fed on diet supplemented with 16 mg/kg Mn
      oxide NPs showed significantly (P<0.05) higher total protein level. The
      antioxidants enzymatic activity (SOD and CAT) metabolic enzymes status in muscle
      and hepatopancreas showed no significant (P>0.05) alterations in prawns fed with
      3.0-18 mg/kg of Mn-oxide NPs supplemented diets. Consequently, the present work
      proposed that 16 mg/kg of Mn-oxide NPs could be supplemented for flexible
      enhanced survival, growth and production of M. rosenbergii. Therefore, the data
      of the present study recommend the addition of 16 mg/kg of Mn-oxide NPs diet to
      developed prawn growth and antioxidant defense system.

PMID- 27049123
TI  - Basal and copper-induced expression of metallothionein isoform 1,2 and 3 genes in
      epithelial cancer cells: The role of tumor suppressor p53.
AB  - Metallothioneins (MTs) are a ubiquitous low-molecular weight, cysteine rich
      proteins with a high affinity for metal ions. The expression and induction of MTs
      have been associated with protection against DNA damage, oxidative stress, and
      apoptosis. Our past research had shown that p53 is an important factor in metal
      regulation of MTs. The present study was undertaken to explore further the
      interrelationship between p53 and MTs. We investigated whether silencing of p53
      could affect expression pattern of basal and copper induced metallothioneins. The
      silencing of wild-type p53 (wt-p53) in epithelial breast cancer MCF7 cells
      affected the basal level of MT-2A RNA, whereas the levels of MT-1A and MT-1X RNA
      remained largely unchanged. The expression of MT-3 was undetectable in MCF7 with
      either functional or silenced p53. MCF7 cells with silenced wt-p53 failed to
      upregulate MT-2A in response to copper and showed a reduced sensitivity toward
      copper induced cell apoptotic death. Similarly in MCF7-E6 and MDA-MB-231 cells,
      the presence of inactive/mutated p53 halted MT-1A and MT-2A gene expression in
      response to copper. Constitutive expression of MT-3 RNA was detectable in the
      presence of mutated p53 (mtp53). Transient transfection of MDA-MB-231 cells with
      wt-p53 enabled copper induced upregulation of both MT-1A and MT-2A but not basal
      level of MT-2A, MT-1E, MT-1X and MT-3. Inactivation of p53 in HepG2 cells
      amplified the basal expression of studied MT isoforms, including MT-3, as well as
      copper-induced mRNA expression of MTs except MT-1H and MT-3. Presented data
      demonstrate a direct relation between p53 and MT-1A and MT-2A and they also
      indicate that wt-p53 might be a negative regulator of MT-3 in epithelial cancer
      cells. 

PMID- 27049124
TI  - Tissue accumulation and urinary excretion of Cr in chromium picolinate (CrPic)
      supplemented lambs.
AB  - Chromium (Cr) concentrations in liver, kidney, spleen, heart, lymph node,
      skeletal muscle, bone, testis and urine of lambs were measured to trace the
      biodistribution and bioaccumulation of Cr after oral supplementation with
      chromium picolinate (CrPic). Twenty-four Santa Ines lambs were treated with four
      different concentrations of CrPic: placebo, 0.250, 0.375 and 0.500 mg of
      CrPic/animal/day for 84 days. The basal diet consisted of Panicum maximum cv
      Massai hay and concentrate. Cr concentrations were measured by ICP-MS measuring
      (52)Cr as collected mass. There was a positive linear relationship between dose
      administered and the accumulation of Cr in the heart, lungs and testis. Urinary
      excretion of Cr occurred in a time and dose-dependent manner, so the longer or
      more dietary Cr provided, the greater excretion of the element. As some non
      carcass components (such as lungs or heart) are added to bone and visceral meal
      to feed animals, there is a risk of bioaccumulation and biomagnification due to
      Cr offered as CrPic in the diet.

PMID- 27049125
TI  - Dietary intake of metals by the young adult population of Eastern Poland: Results
      from a market basket study.
AB  - Dietary intake of macro-, trace and toxic elements was determined among the young
      adult population of Eastern Poland. The study was performed in 2011-2013 and
      involved 583 participants living in Lublin and its province. Dietary intakes of
      metals were determined using a 24h dietary recall technique and a market basket
      method. The analytical quantification of As, Ca, Cd, Cu, Fe, K, Mg, Mn, Mo, Na,
      Ni, Pb, Se and Zn was performed using ICP-MS technique, whereas the content of
      mercury was determined using the Mercury Analyzer. Performed investigations
      revealed that daily dietary intakes of the majority of the study elements (macro-
      and trace) and toxic elements such as As, Pb or Hg are within the range of
      reference values. However, high consumption of Na and improper Na/K ratio
      combined with low intake of Mg may be harmful to the health of the population.
      Moreover, obtained data suggest that the risk of developing diseases among
      population in Eastern Poland related to high exposure to Ni and Cd absorbed from
      foodstuffs was high. 

PMID- 27049126
TI  - Arsenic and dichlorvos: Possible interaction between two environmental
      contaminants.
AB  - Metals are ubiquitously present in the environment and pesticides are widely used
      throughout the world. Environmental and occupational exposure to metal along with
      pesticide is an area of great concern to both the public and regulatory
      authorities. Our major concern is that combination of these toxicant present in
      environment may elicit toxicity either due to additive or synergistic
      interactions or 'joint toxic actions' among these toxicants. It poses a rising
      threat to human health. Water contamination particularly ground water
      contamination with arsenic is a serious problem in today's scenario since arsenic
      is associated with several kinds of health problems, such arsenic associated
      health anomalies are commonly called as 'Arsenism'. Uncontrolled use and spillage
      of pesticides into the environment has resulted in alarming situation. Moreover
      serious concerns are being addressed due to their persistence in the
      environmental matrices such as air, soil and surface water runoff resulting in
      continuous exposure of these harmful chemicals to human beings and animals. Bio
      availability of these environmental toxicants has been enhanced much due to
      anthropological activities. Dreadfully very few studies are available on combined
      exposures to these toxicants on the animal or human system. Studies on the acute
      and chronic exposure to arsenic and DDVP are well reported and well defined.
      Arsenic is a common global ground water contaminant while dichlorvos is one of
      the most commonly and widely employed organophosphate based insecticide used in
      agriculture, horticulture etc. There is thus a real situation where a human may
      get exposed to these toxicants while working in a field. This review highlights
      the individual and combined exposure to arsenic and dichlorvos on health. 

PMID- 27049127
TI  - Trace metal levels in serum and urine of a population in southern Brazil.
AB  - This study aimed to evaluate serum and urine concentrations of several trace
      metals of a non-directly exposed population in southern Brazil and establish
      reference values. Serum and urine samples were obtained from 240 volunteers (175
      males and 65 females, age ranging from 18 to 74 years old). Levels of arsenic,
      chromium, cobalt, copper, lead, nickel, manganese and zinc were determined by
      means of dynamic reaction cell inductively coupled plasma mass spectrometry (DRC
      ICP-MS). Comparison between genders resulted in no significant difference for all
      metals but serum copper, as concentrations are higher in females than males. For
      most metals assessed, a negative correlation between serum concentrations and age
      was found, but no significant correlation was found between urine concentrations
      and age. 

PMID- 27049128
TI  - Iron-induced skeletal muscle atrophy involves an Akt-forkhead box O3-E3 ubiquitin
      ligase-dependent pathway.
AB  - Skeletal muscle wasting or sarcopenia is a critical health problem. Skeletal
      muscle atrophy is induced by an excess of iron, which is an essential trace metal
      for all living organisms. Excessive amounts of iron catalyze the formation of
      highly toxic hydroxyl radicals via the Fenton reaction. However, the molecular
      mechanism of iron-induced skeletal muscle atrophy has remained unclear. In this
      study, 8-weeks-old C57BL6/J mice were divided into 2 groups: vehicle-treated
      group and the iron-injected group (10 mg iron day(-1)mouse(-1)) during 2 weeks.
      Mice in the iron-injected group showed an increase in the iron content of the
      skeletal muscle and serum and ferritin levels in the muscle, along with reduced
      skeletal muscle mass. The skeletal muscle showed elevated mRNA expression of the
      muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger
      1(MuRF1), on days 7 and 14 of iron treatment. Moreover, iron-treated mice showed
      reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles.
      Inhibition of FOXO3a using siRNA in vitro in C2C12 myotube cells inhibited iron
      induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube
      diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor
      abrogated iron-induced muscle atrophy by reactivating the Akt-FOXO3a pathway.
      Iron-induced skeletal muscle atrophy is suggested to involve the E3 ubiquitin
      ligase mediated by the reduction of Akt-FOXO3a signaling by oxidative stress.

PMID- 27049129
TI  - Iron absorption after introducing and discontinuation of iron and zinc
      supplementation in rats.
AB  - The aim of this study was to investigate the changes in iron apparent absorption
      (IAA%) during and after iron and zinc supplementation in rats. The study was
      conducted on 6-week old male Wistar rats in 3 stages: 4-week period of adaptation
      to the control (C) and iron deficient (D) diets (stage I); 4-week period of
      supplementation with 10-time more iron (CSFe, DSFe), zinc (CSZn, DSZn) or both
      iron and zinc (CSFeZn, DSFeZn) compared to C diet (stage II); 2-week of post
      supplementation period (rats were fed the same diets as in the adaptation period,
      stage III). IAA% was measured in five consecutive days directly after introducing
      and discontinuation of iron and zinc supplementation as well as in the end of
      stage II (days: 22-24th) and stage III (days: 8-10th). Overall in the second day
      after introducing and in the fifth day after discontinuation of iron or iron and
      zinc supplementation, the IAA% had undergone to the level compatible with the
      values in the end of each stage. At the end of stage II, IAA% in CSFeZn (54.1 +/-
      2.7%) rats was not different from the IAA% in CSFe rats (53.9 +/- 1.9%), but in
      DSFeZn group IAA% (49.4 +/- 2.1%) was significantly lower than in DSFe (57.4 +/-
      2.3%) group. Moreover, IAA% after stage II and stage III in DSZn group was
      significantly lower (39.2 +/- 2.8% and 38.6 +/- 2.6%, respectively) than in group
      D (60.7 +/- 1.9% and 54.3 +/- 3.0%, respectively). In conclusion, zinc
      administered simultaneously with iron (Zn:Fe weight ratio=1:1) decreased IAA% in
      adult rats fed on iron deficient diet, but not in rats fed on control diet. IAA%
      reduction by zinc supplementation has been extended to 10 days after
      discontinuation of the treatment. Adaptation of the rats to high doses of iron or
      iron and zinc and also to the cessation of these treatments was relatively fast.
      However, IAA% was stabilized faster after introducing the supplementation than
      it's discontinuation.

PMID- 27049130
TI  - Copper toxicosis in non-COMMD1 Bedlington terriers is associated with metal
      transport gene ABCA12.
AB  - Wilson's disease, caused by a mutation in the ATP-ase 7B gene, is the only
      genetically characterised human disease with inhibition of biliary copper
      excretion and toxic copper accumulation in liver and occasionally brain. A
      similar copper toxicosis occurs in Bedlington terriers (CT) with liver damage
      only. Although CT has been associated with a defect in the COMMD1 gene (COMMD1
      (del/del)), Bedlington terriers with CT and lacking this mutation are also
      recognised (non-COMMD1 (del/del)). A study was designed to identify any other
      gene polymorphisms associated with copper toxicity in Bedlington terriers
      employing genome wide association studies (GWAS) followed by deep sequencing of
      the candidate region. Blood for DNA analysis and liver for confirmation of the
      diagnosis was obtained from 30 non-COMMD1 (del/del) Bedlington terriers
      comprising equal numbers of CT-affected dogs and controls. DNA was initially
      subjected to GWAS screening and then further sequencing to target the putative
      mutant gene. The study has identified a significant disease association with a
      region on chromosome 37 containing identified SNP's which are highly
      significantly associated with non-COMMD1 (del/del) Bedlington terrier CT. This
      region contains the ABCA12 gene which bears a close functional relationship to
      ATP-ase 7B responsible for Wilson's disease in man. 

PMID- 27049131
TI  - Spectrophotometric evaluation of selenium binding by Saccharomyces cerevisiae
      ATCC MYA-2200 and Candida utilis ATCC 9950 yeast.
AB  - In this study, the ability of selenium binding the biomas of Saccharomyces
      cerevisiae ATCC MYA-2200 and Candida utilis ATCC 9950 was investigated. Sodium
      selenite(IV) salts were added to the experimental media at concentrations of 10,
      20, 40, and 60 mg Se(4+) L(-1). In the tested concentration range, one
      concentration reported a significant reduction in the biomass yield of both yeast
      strains. Intense growth was observed for C. utilis yeast, which reached the
      highest biomass yield of 15 gd.w.L(-1) after 24h cultivation in the presence of
      10mg Se(4+) L(-1). Based on the use of spectrophotometric method for the
      determination of selenium content by using Variamine Blue as a chromogenic agent,
      efficient accumulation of this element in the biomass of the investigated yeast
      was observed. The highest amount of selenium, that is, 5.64 mg Se(4+)gd.w.(-1),
      was bound from the environment by S. cerevisiae ATCC MYA-2200 cultured in the
      presence of 60 mg Se(4+) L(-1) medium 72h Slightly less amount, 5.47 mg Se(4+)
      gd.w.(-1), was absorbed by C. utilis ATCC 9950 during similar cultural
      conditions. Based on the results of the biomass yield and the use of selenium
      from the medium, it can be observed that yeasts of the genus Candida are more
      efficient in binding this element, and this property finds practical application
      in the production of selenium-enriched yeast.

PMID- 27049132
TI  - Element bioimaging of liver needle biopsy specimens from patients with Wilson's
      disease by laser ablation-inductively coupled plasma-mass spectrometry.
AB  - A laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method
      is developed and applied for the analysis of paraffin-embedded liver needle
      biopsy specimens of patients with Wilson's disease (WD), a rare autosomal
      recessive disorder of the copper metabolism causing various hepatic, neurological
      and psychiatric symptoms due to a copper accumulation in the liver and the
      central nervous system. The sample set includes two WD liver samples and one
      negative control sample. The imaging analysis was performed with a spatial
      resolution of 10 MUm. Besides copper, iron was monitored because an elevated iron
      concentration in the liver is known for WD. In addition to this, both elements
      were quantified using an external calibration based on matrix-matched gelatine
      standards. The presented method offers low limits of detection of 1 and 5 MUg/g
      for copper and iron, respectively. The high detection power and good spatial
      resolution allow the analysis of small needle biopsy specimen using this method.
      The two analyzed WD samples can be well differentiated from the control sample
      due to their inhomogeneous copper distribution and high copper concentrations of
      up to 1200 MUg/g. Interestingly, the WD samples show an inverse correlation of
      regions with elevated copper concentrations and regions with high iron
      concentrations.

PMID- 27049133
TI  - Trace elements levels in centenarian 'dodgers'.
AB  - Trace element bioavailability can play a role in several metabolic and
      physiological pathways known to be altered during the aging process. We aimed to
      explore the association of trace elements with increased lifespan by analyzing
      the circulating levels of seven trace elements (Cr, Cu, Fe, Mn, Mo, Se and Zn) in
      a cohort of healthy centenarians or 'dodgers' (>=100 years, free of major age
      related diseases) in comparison with sex-matched younger elderly controls.
      Centenarians showed significant lower Cu (783.7 (76.7, 1608.9) vs 962.5 (676.3,
      2064.4)MUg/mL, P<0.001), but higher Fe (1.3 (0.4, 4.7) vs 1.1 (0.5, 8.4)MUg/mL,
      P=0.003) and Se (85.7 (43.0, 256.7) vs 77.8 (24.3, 143.8)ng/mL, P=0.002) values
      compared with elderly controls. The logistic regression analysis identified the
      combination of Cu and Se as significant predictor variables associated with
      successful aging (P=0.001), while receiver operating characteristic (ROC)
      analysis confirmed that Cu and Se (either alone or in combination) were
      independent variables associated with healthy aging. An 'improved' trace element
      profile (reduced Cu and elevated Se, which are involved in key physiological
      processes) could play a role in the resistance to disease showed by centenarian
      'dodgers', and, therefore, at least partly, be involved in the healthy aging
      phenotype shown by these subjects. These results should be confirmed in larger
      cohorts of other geographic/ethnic origin and the potential cause-effect
      association tested in mechanistic experimental settings. 

PMID- 27049134
TI  - Dietary copper and human health: Current evidence and unresolved issues.
AB  - Although copper (Cu) is recognized as an essential trace element, uncertainties
      remain regarding Cu reference values for humans, as illustrated by discrepancies
      between recommendations issued by different national authorities. This review
      examines human studies published since 1990 on relationships between Cu intake,
      Cu balance, biomarkers of Cu status, and health. It points out several gaps and
      unresolved issues which make it difficult to assess Cu requirements. Results from
      balance studies suggest that daily intakes below 0.8 mg/day lead to net Cu
      losses, while net gains are consistently observed above 2.4 mg/day. However,
      because of an incomplete collection of losses in all studies, a precise
      estimation of Cu requirements cannot be derived from available data. Data
      regarding the relationship between Cu intake and potential biomarkers are either
      too preliminary or inconclusive because of low specificity or low sensitivity to
      change in dietary Cu over a wide range of intakes. Results from observation and
      intervention studies do not support a link between Cu and a risk of
      cardiovascular disease, cognitive decline, arthritis or cancer for intakes
      ranging from 0.6 to 3mg/day, and limited evidence exists for impaired immune
      function in healthy subjects with a very low (0.38 mg/day) Cu intake. However,
      data from observation studies should be regarded with caution because of
      uncertainties regarding Cu concentration in various foods and water. Further
      studies that accurately evaluate Cu exposure based on reliable biomarkers of Cu
      status are needed.

PMID- 27049135
TI  - Corrigendum to "Nickel allergy and relationship with Staphylococcus aureus in
      atopic dermatitis" [J. Trace Elem. Med. Biol. 33 (2016) 1-7].

PMID- 27049136
TI  - mTOR pathway inhibition as a new therapeutic strategy in epilepsy and
      epileptogenesis.
AB  - Several preclinical and some clinical studies have revealed that the mammalian
      target of rapamycin (mTOR) signaling pathway is involved in both genetic and
      acquired epilepsy syndromes. Excessive activation of mTOR signaling, as a
      consequence of loss-of-function of genes encoding for tuberous sclerosis complex
      (TSC) 1 and 2, is linked to the development of cortical malformations and
      epilepsy. This mTOR hyperactivation is associated with different epileptogenic
      conditions under the term of 'mTORopathies' such as tuberous sclerosis, focal
      cortical dysplasia, hemimegalencephaly and ganglioglioma. mTOR overactivation
      produces brain abnormalities that include dysplastic neurons, abnormal cortical
      organization and astrogliosis. mTOR inhibitors (e.g. rapamycin) have consistent
      protective effects in various genetic (e.g. TSC models and WAG/Rij rats) and
      acquired (e.g. kainate or pilocarpine post-status epilepticus) epilepsy animal
      models. Furthermore, clinical studies in patients with TSC and cortical dysplasia
      (CD) have confirmed the effectiveness of mTOR inhibitors also in epileptic
      patients. Therefore, mTOR is currently a very good candidate as a target for
      epilepsy and epileptogenesis. This review describes the relevance of the mTOR
      pathway to epileptogenesis and its potential as a therapeutic target in epilepsy
      treatment by presenting the most recent findings on mTOR inhibitors.

PMID- 27049137
TI  - Editorial: The Need for Evidence-based Medicine for Improving Oral Health
      Strategies.

PMID- 27049138
TI  - Iodine-mediated etching of gold nanorods for plasmonic sensing of dissolved
      oxygen and salt iodine.
AB  - Here, we have carefully investigated iodine-mediated etching of gold nanorods
      (AuNRs) in the presence of iodate and applied this phenomenon to on-site
      detection of dissolved oxygen (DO). Under given conditions, the quantitative
      conversion of target analytes DO to iodine leads to the etching of AuNRs along
      the longitudinal direction with the aid of cetyltrimethylammonium. As a result,
      the longitudinal localized surface plasmon resonance shifts to a short
      wavelength. The peak-shift can be used for quantitative determination of DO and
      iodate by a spectrophotometer. The satisfactory results from DO detection in
      different water samples and iodate detection in table salt indicate the
      feasibility of the proposed methods. Moreover, the as-prepared colorimetric test
      paper would make the detection more economical and simpler.

PMID- 27049139
TI  - Ru(ii) polypyridyl complex-incorporated and folate-conjugated vehicle for cancer
      cell imaging and photoinduced inactivation.
AB  - Ru(ii) polypyridyl complexes have been expected as promising therapeutic agents
      against cancer owing to its DNA photocleavage activity. However, the lack of cell
      selectivity poses a significant obstacle to their practical application. Herein,
      the strategy combining cell-specific imaging with photoinduced cell death based
      on [Ru(phen)2(dppz)](2+) has been developed by incorporating
      [Ru(phen)2(dppz)](2+) into folate-conjugated liposomes. The cells overexpressing
      folate receptors could specifically recognize this vehicle and be imaged through
      the luminescence of [Ru(phen)2(dppz)](2+). Thereafter, the delivered
      [Ru(phen)2(dppz)](2+) interacted with DNA in cells and led to photoinduced cell
      death. This work provided a possible alternative for cancer diagnosis and
      therapy.

PMID- 27049140
TI  - Metal free carboamination of internal alkynes--an easy access to polysubstituted
      quinolines.
AB  - A metal free carboamination of unactivated alkynes towards highly substituted
      quinolines was realized in the presence of a synergistic Bronsted acid catalyst
      system. Supported by mechanistic probes, the reaction proceeds via a highly
      reactive vinyl cation in a C-C bond formation--Schmidt reaction sequence. The
      irreversible extrusion of N2, as a powerful driving force, allows for a general
      conversion of poorly nucleophilic aliphatic alkynes.

PMID- 27049141
TI  - Solvo-thermal microwave-powered two-dimensional material exfoliation.
AB  - We report our discovery of a universal, ultrafast, green, solvo-thermal
      technology for producing excellent quality, large-sized, few-layered nanosheets
      from well-known two-dimensional materials (TDMs) such as hexagonal boron nitride
      (h-BN), graphite, and MoS2. Our theory confirms the basis of this novel technique
      for exfoliation of high-quality, layered TDMs by unraveling a hitherto unknown
      role of the solvent. 

PMID- 27049142
TI  - One-step in situ synthesis of CeO2 nanoparticles grown on reduced graphene oxide
      as an excellent fluorescent and photocatalyst material under sunlight
      irradiation.
AB  - CeO2 nanoparticles (NPs) with average particle size of ~17 nm were grown on
      graphene sheets by simply mixing cerium chloride as the Ce precursor with
      graphene oxide (GO) in distilled water and the simultaneous reduction of GO to
      reduced graphene oxide (rGO), followed by a one-step hydrothermal treatment at
      150  degrees C. A unique blue to green tuneable luminescence was observed as a
      function of the excitation wavelength. With this method, significant applications
      of rGO-CeO2 nanocomposites in many optical devices could be realized. The
      photocatalytic activity of the as-synthesized CeO2 and rGO-CeO2 nanocomposite was
      investigated by monitoring the degradation of methylene blue (MB) dye under
      direct sunlight irradiation. The rGO-CeO2 nanocomposite exhibited excellent
      photocatalytic activity compared to CeO2 NPs by degrading 90% of the MB dye in 10
      min irradiation under sunlight. This property of rGO-CeO2 nanocomposites was
      ascribed to the significant suppression of the recombination rate of photo
      generated electron-hole pairs due to charge transfer between rGO sheets and CeO2
      NPs and the smaller optical band-gap in the rGO-CeO2 nanocomposite. 

PMID- 27049143
TI  - Effects of Pt dispersion on electronic and oxide ionic conductivity in
      Pr1.90Ni0.71Cu0.24Ga0.05O4.
AB  - The effects of dispersing Pt particles in bulk Pr1.90Ni0.71Cu0.21Ga0.05O(4+delta)
      (PNCG) on the electrical conductivity and oxygen permeability of the material
      were studied. The different thermal expansion coefficients of PNCG and Pt
      generated a mechanical compressive strain in the PNCG. This may cause the
      electrical conductivity to decrease in samples containing Pt. In contrast, the
      oxide ion conductivity estimated from the oxygen permeability increased upon
      dispersion of Pt. These variations appear to be related to the electron hole and
      interstitial oxygen concentrations. Moreover, the present study suggests that the
      mechanical strain induces a chemical strain via the introduction of oxygen
      defects as well as changes in cation valences.

PMID- 27049144
TI  - Authors' reply.

PMID- 27049145
TI  - Authors' reply.

PMID- 27049146
TI  - Guest Editorial for the  13th Asia Pacific Bioinformatics Conference.

PMID- 27049147
TI  - [Not Available].

PMID- 27049148
TI  - Mole's Wow! So now you have your own lab! Part VII--Beaten and bruised. By
      Caveman.

PMID- 27049149
TI  - [Not Available].

PMID- 27049150
TI  - [Not Available].

PMID- 27049151
TI  - [Not Available].

PMID- 27049152
TI  - Introduction to the Special Section on Engineering   Sciences for Biology and
      Medicine Conference   (ESBM 2015).

PMID- 27049153
TI  - [Not Available].

PMID- 27049154
TI  - [Ohrtamponade superfluous?].

PMID- 27049155
TI  - How well do glucose variability measures predict  patient glycaemic outcomes
      during treatment  intensification in type 2 diabetes?
AB  - AIM: Despite links to clinical outcomes in patients with type 2 diabetes mellitus
      (T2DM), the clinical utility of glycaemic variability (GV) measures is unknown.
      We evaluated the correlation between baseline GV, and glycated haemoglobin
      (HbA1c) attainment and hypoglycaemic events during treatment intensification in a
      large group of patients. METHODS: Patient-level data from six 24-week clinical
      trials of T2DM patients undergoing treatment intensification with basal insulin
      or comparators (N = 1699) were pooled. Baseline GV measures included standard
      deviation (SD), mean amplitude of glycaemic excursions (MAGE), mean absolute
      glucose (MAG), coefficient of variation (CV), high blood glucose index (HBGI),
      and low blood glucose index (LBGI) and were correlated with HbA1c change and
      hypoglycaemic events. RESULTS: All mean GV measures, excluding CV which worsened,
      improved significantly from baseline to Week 24, with the largest proportional
      reduction obtained for HBGI (-65.5%). When assessed as mean individual percentage
      changes, only HBGI improved significantly. Baseline GV correlated positively with
      Week 24 HbA1c for SD, MAGE, and HBGI. Baseline HBGI and CV correlated negatively
      and positively, respectively, with Week 24 HbA1c change. Correlations also
      existed between most baseline GV measures and age, body mass index, Week 24
      fasting plasma glucose, Week 24 postprandial plasma glucose, and hypoglycaemic
      events; statistical significance depended on the specific measure. CONCLUSIONS:
      Pre-treatment GV is associated with glycaemic outcomes in T2DM patients
      undergoing treatment intensification over 24 weeks. HBGI might be the most robust
      predictor, warranting validation in dedicated prospective studies or randomized
      trials to assess the predictive value of measuring GV.

PMID- 27049156
TI  - A new horizon of cerebral white matter hyperintensity in   geriatric medicine.

PMID- 27049157
TI  - Patient-centered care: A short-term investment for a long-term return.

PMID- 27049158
TI  - Overhaul your HIPAA privacy notice. Modifying this document can help both
      practice and patients.

PMID- 27049160
TI  - Workers' compensation changes made.

PMID- 27049159
TI  - Election issue. 1. Protect our penalty rates.

PMID- 27049161
TI  - Queensland midwives struggle to take time out for professional development.

PMID- 27049162
TI  - QNU joins review on industrial relations system.

PMID- 27049163
TI  - A ROCK AND A HARD PLACES.

PMID- 27049164
TI  - Genome engineering - Matching supply with demand.

PMID- 27049165
TI  - Multimodal Upconversion Nanoplatform with a Mitochondria-Targeted Property for
      Improved Photodynamic Therapy of Cancer Cells.
AB  - Upconversion nanoparticles (UCNPs) with the capacity to emit high-energy visible
      or UV light under low-energy near-infrared excitation have been extensively
      explored for biomedical applications including imaging and photodynamic therapy
      (PDT) against cancer. Enhanced cellular uptake and controlled subcellular
      localization of a UCNP-based PDT system are desired to broaden the biomedical
      applications of the system and to increase its PDT effect. Herein, we build a
      multimodal nanoplatform with enhanced therapeutic efficiency based on 808 nm
      excited NaYbF4:Nd@NaGdF4:Yb/Er@NaGdF4 core-shell-shell nanoparticles that have a
      minimized overheating effect. The photosensitizer pyropheophorbide a (Ppa) is
      loaded onto the nanoparticles capped with biocompatible polymers, and the
      nanoplatform is functionalized with transcriptional activator peptides as
      targeting moieties. Significantly increased cellular uptake of the nanoparticles
      and dramatically elevated photocytotoxicity are achieved. Remarkably,
      colocalization of Ppa with mitochondria, a crucial subcellular organelle as a
      target of PDT, is proven and quantified. The subsequent damage to mitochondria
      caused by this colocalization is also confirmed to be significant. Our work
      provides a comprehensively improved UCNP-based nanoplatform that maintains great
      biocompatibility but shows higher photocytotoxicity under irradiation and
      superior imaging capabilities, which increases the biomedical values of UCNPs as
      both nanoprobes and carriers of photosensitizers toward mitochondria for PDT. 

PMID- 27049166
TI  - Reductive Hydrazination with Trichlorosilane: A Method for the Preparation of 1,1
      Disubstituted Hydrazines.
AB  - A straightforward and facile method has been developed to prepare 1,1
      disubstituted hydrazines via Lewis base promoted direct reductive hydrazination.
      Under the catalysis of hexamethylphosphoramide (HMPA) and N,N-dimethylacetamide
      (DMAc), respectively, various ketones and aldehydes could react with
      phenylhdrazines to prepare 1,1-disubstituted hydrazines with good to high yields.

PMID- 27049167
TI  - Transfer of Microparticles across Laminar Streams from Non-Newtonian to Newtonian
      Fluid.
AB  - Engineering inertial lift forces and elastic lift forces is explored to transfer
      microparticles across laminar streams from non-Newtonian to Newtonian fluid. A co
      stream of non-Newtonian flow loaded with microparticles (9.9 and 2.0 MUm in
      diameter) and a Newtonian carrier medium flow in a straight rectangular conduit
      is devised. The elastic lift forces present in the non-Newtonian fluid,
      undeterred by particle-particle interaction, successfully pass most of the larger
      (9.9 MUm) particles over to the Newtonian fluid. The Newtonian fluid takes over
      the larger particles and focus them on the equilibrium position, separating the
      larger particles from the smaller particles. This mechanism enabled processing of
      densely suspended particle samples. The method offers dilution-free (for number
      densities up to 10,000 MUL(-1)), high throughput (6700 beads/s), and highly
      efficient (>99% recovery rate, >97% purity) particle separation operated over a
      wide range of flow rate (2 orders of magnitude).

PMID- 27049168
TI  - alpha-Pinene Autoxidation Products May Not Have Extremely Low Saturation Vapor
      Pressures Despite High O:C Ratios.
AB  - COSMO-RS (conductor-like screening model for real solvents) and three different
      group-contribution methods were used to compute saturation (subcooled) liquid
      vapor pressures for 16 possible products of ozone-initiated alpha-pinene
      autoxidation, with elemental compositions C10H16O4-10 and C20H30O10-12. The
      saturation vapor pressures predicted by the different methods varied widely.
      COSMO-RS predicted relatively high saturation vapor pressures values in the range
      of 10(-6) to 10(-10) bar for the C10H16O4-10 "monomers", and 10(-11) to 10(-16)
      bar for the C20H30O10-12 "dimers". The group-contribution methods predicted
      significantly (up to 8 order of magnitude) lower saturation vapor pressures for
      most of the more highly oxidized monomers. For the dimers, the COSMO-RS
      predictions were within the (wide) range spanned by the three group-contribution
      methods. The main reason for the discrepancies between the methods is likely that
      the group-contribution methods do not contain the necessary parameters to
      accurately treat autoxidation products containing multiple hydroperoxide, peroxy
      acid or peroxide functional groups, which form intramolecular hydrogen bonds with
      each other. While the COSMO-RS saturation vapor pressures for these systems may
      be overestimated, the results strongly indicate that despite their high O:C
      ratios, the volatilities of the autoxidation products of alpha-pinene (and
      possibly other atmospherically relevant alkenes) are not necessarily extremely
      low. In other words, while autoxidation products are able to adsorb onto aerosol
      particles, their evaporation back into the gas phase cannot be assumed to be
      negligible, especially from the smallest nanometer-scale particles. Their
      observed effective contribution to aerosol particle growth may therefore involve
      rapid heterogeneous reactions (reactive uptake) rather than effectively
      irreversible physical absorption.

PMID- 27049169
TI  - Development of a Response Inconsistency Scale for the Personality Inventory for
      DSM-5.
AB  - The advent of a dimensional model of personality disorder included in DSM-5 has
      necessitated the development of a new measurement scheme, specifically a self
      report questionnaire termed the Personality Inventory for DSM-5 (PID-5; Krueger,
      Derringer, Markon, Watson, & Skodol, 2012 ). However, there are many threats to
      the validity of a self-report measure, including response inconsistency. This
      study outlines the development of an inconsistency scale for the PID-5. Across
      both college student and clinical samples, the inconsistency scale was able to
      reliably differentiate real from random responding. Random responses led to
      increased scores on the PID-5 facets, indicating the importance of detecting
      inconsistent responding prior to test interpretation. Thus, this inconsistency
      scale could be of use to researchers and clinicians in detecting inconsistent
      responses to this new personality disorder measure.

PMID- 27049171
TI  - Correctional Nursing Interventions for Incarcerated Persons with Mental
      Disorders: An Integrative Review.
AB  - The authors explore the current state-of-the art of correctional nursing by
      summarizing the types of interventions employed by nurses, across studies,
      designed to assist this challenging group of patients. This examination of
      evidence-based interventions implemented and tested by correctional nurses
      provides a better understanding of their role and function. Correctional health
      is a nurse driven system, yet a minimal amount is known about the nurses who
      practice in these environments or about their contributions to the practice of
      mental health nursing in correctional environments. An integrative review
      utilizing PRISMA guidelines examined five databases (Medline/PubMed, PsycInfo,
      PsychArticles, Sage Criminology, and Academic Search) for peer-reviewed articles
      that fit selected criteria. Of 324 references identified, 16 studies met
      criteria. Following assessment of strength of evidence, only eight studies
      offered scientific proof of the effectiveness of nursing interventions. Nursing
      interventions implemented in correctional settings targeted incarcerated persons
      with behavioral and psychological symptoms. Interventions included psycho
      education, environmental adaptations, and behavior therapies. The centrality of
      nurses in correctional health care emphasizes the significance of understanding
      their role and function in this setting. This integrative review revealed that
      correctional nurses are actively engaged in providing therapeutic, evidence-based
      interventions in the health care of incarcerated persons. Of interest, seven of
      the eight studies focused on incarcerated persons with mental health or substance
      use issues. Nurse led interventions such as CBT, labyrinth walking, and yoga aim
      to improve coping and adaptation of incarcerated persons. 

PMID- 27049170
TI  - Usual care and management of fall risk increasing drugs in older dizzy patients
      in Dutch general practice.
AB  - OBJECTIVE: For general practitioners (GPs) dizziness is a challenging condition
      to deal with. Data on the management of dizziness in older patients are mostly
      lacking. Furthermore, it is unknown whether GPs attempt to decrease Fall Risk
      Increasing Drugs (FRIDs) use in the management of dizziness in older patients.
      The aim of this study is to gain more insight into GP's management of dizziness
      in older patients, including FRID evaluation and adjustment. DESIGN: Data were
      derived from electronic medical records, obtained over a 12-month period in 2013.
      SETTING: Forty-six Dutch general practices. PATIENTS: The study sample comprised
      of 2812 older dizzy patients of 65 years and over. Patients were identified using
      International Classification of Primary Care codes and free text. MAIN OUTCOME
      MEASURES: Usual care was categorized into wait-and-see strategy (no treatment
      initiated); education and advice; additional testing; medication adjustment; and
      referral. RESULTS: Frequently applied treatments included a wait-and-see strategy
      (28.4%) and education and advice (28.0%). Additional testing was performed in
      26.8%; 19.0% of the patients were referred. Of the patients 87.2% had at least
      one FRID prescription. During the observation period, GPs adjusted the use of one
      or more FRIDs for 11.7% of the patients. CONCLUSION: This study revealed a wide
      variety in management strategies for dizziness in older adults. The referral rate
      for dizziness was high compared to prior research. Although many older dizzy
      patients use at least one FRID, FRID evaluation and adjustment is scarce. We
      expect that more FRID adjustments may reduce dizziness and dizziness-related
      impairment. Key Points It is important to know how general practitioners manage
      dizziness in older patients in order to assess potential cues for improvement.
      This study revealed a wide variety in management strategies for dizziness in
      older patients. There was a scarcity in Fall Risk Increasing Drug (FRID)
      evaluation and adjustment. The referral rate for dizziness was high compared with
      previous research.

PMID- 27049173
TI  - High prevalence of HIV p24 antigen among HIV antibody negative prospective blood
      donors in Ile-Ife, Nigeria.
AB  - Blood transfusion service centers in Nigeria screen donated blood for markers of
      HIV infection using antibody- (Ab) based rapid test and in some centers,
      positives are re-tested using Ab-based ELISA. Paucity of data exists on p24
      antigen prevalence among HIV Ab-negative donors in Nigeria. This study aims at
      detecting HIV p24 antigen among prospective blood donors in Osun State, Nigeria.
      Prospective blood donors negative for HIV antibodies using Determine test kit
      were re-tested using BIORAD GENSCREEN Ultra Ag-Ab ELISA kit, a fourth-generation
      ELISA kit that detects HIV antibodies/p24 antigen. Of the 169 HIV Ab-negative
      prospective donors, 10 (5.9%) were positive for HIV p24 antigen and 70% (7/10) of
      them were in the age range 18-30 years. Results of this study show that blood
      transfusion is still one of the major routes of HIV transmission in Nigeria and a
      higher proportion is among youth. Inclusion of p24 antigen testing into the blood
      donor screening will help reduce transfusion associated HIV in Nigeria if Nucleic
      Acid Testing (NAT) of all blood donor samples is not affordable; also, HIV
      enlightenment programs tailored toward youth may help reduce this rate among
      donors since more young people donate blood in low/middle-income countries than
      in high-income countries. 

PMID- 27049175
TI  - Maternal serum ferritin as a clinical tool at 34-36 weeks' gestation for
      distinguishing subgroups of fetal growth restriction.
AB  - OBJECTIVE: To compare maternal ferritin levels across pregnancies with fetal
      growth restriction including SGA and IUGR compared to appropriate for gestational
      age (AGA). METHODS: Three groups were enrolled: AGA, SGA (birth weight below 10th
      percentile for gestational age with no placental insufficiency findings), and
      IUGR (birth weight below 5th percentile for gestational age accompanied by
      abnormal umbilical artery Doppler waveforms and/or oligohydramnios). Maternal
      serum ferritin samples were obtained at gestational weeks 34 through 36, and
      delivery occurred at or beyond 36 weeks. RESULTS: A total of 126 pregnancies with
      AGA (36%), SGA (40%), and IUGR (24%) were enrolled. The mean maternal serum
      ferritin level was higher in the IUGR group than in the AGA group (59 MUg/l
      versus 32.5 MUg/l, p < 0.001). A maternal serum ferritin cutoff of 48 MUg/l was
      found to be optimal for distinguishing between IUGR and AGA with a sensitivity of
      67.7%, specificity of 92%, PPV of 84%, NPV of 82%, diagnostic accuracy of 82.7%,
      LR + of 8 and LR- of 0.3, respectively. CONCLUSION: Maternal serum ferritin
      levels differ in pregnancies with IUGR. The role of maternal serum ferritin
      measurements as a clinical tool for distinguishing different forms of fetal
      growth restriction warrants further investigation.

PMID- 27049174
TI  - A novel antibody discovery platform identifies anti-influenza A broadly
      neutralizing antibodies from human memory B cells.
AB  - Monoclonal antibody isolation directly from circulating human B cells is a
      powerful tool to delineate humoral responses to pathological conditions and
      discover antibody therapeutics. We have developed a platform aimed at improving
      the efficiencies of B cell selection and V gene recovery. Here, memory B cells
      are activated and amplified using Epstein-Barr virus infection, co-cultured with
      CHO-muCD40L cells, and then assessed by functional screenings. An in vitro
      transcription and translation (IVTT) approach was used to analyze variable (V)
      genes recovered from each B cell sample and identify the relevant heavy/light
      chain pair(s). We achieved efficient amplification and activation of memory B
      cells, and eliminated the need to: 1) seed B cells at clonal level (<=1
      cell/well) or perform limited dilution cloning; 2) immortalize B cells; or 3)
      assemble V genes into an IgG expression vector to confirm the relevant
      heavy/light chain pairing. Cross-reactive antibodies targeting a conserved
      epitope on influenza A hemagglutinin were successfully isolated from a healthy
      donor. In-depth analysis of the isolated antibodies suggested their potential
      uses as anti-influenza A antibody therapeutics and uncovered a distinct affinity
      maturation pathway. Importantly, our results showed that cognate heavy/light
      chain pairings contributed to both the expression level and binding abilities of
      our newly isolated VH1-69 family, influenza A neutralizing antibodies,
      contrasting with previous observations that light chains do not significantly
      contribute to the function of this group of antibodies. Our results further
      suggest the potential use of the IVTT as a powerful antibody developability
      assessment tool.

PMID- 27049176
TI  - The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in
      patients with cancer.
AB  - OBJECTIVE: Cisplatin is a potent antineoplastic agent used and its major limiting
      side effect is nephrotoxicity. The aims of the study are early detection of acute
      kidney injury (AKI) with biomarkers and investigation of the potential nephron
      protective effects of theophylline. METHODS: Glomerular filtration rates (GFR),
      neutrophil gelatinase-associated lipocalin (NGAL), cystatin C were measured at
      5th day of treatment in all of the patients. In addition, these parameters were
      measured repeatedly after the administration of cisplatin, at 2nd hour, 5th and
      20th days. PATIENTS: Sixty patients who are planned to receive cisplatin for the
      first time were included in the study. Patients were divided into two groups as
      Group 1 (n = 30) (standard treatment arm) and Group II (n = 30) (theophylline
      arm). RESULTS: In both groups after the administration of cisplatin, GFR showed a
      significant decrease within time (p = 0.006). Urine NGAL levels were
      significantly high after 2 h of cisplatin administration (p < 0.001), no
      significant difference was observed between groups. However, when the time*group
      effects were considered together, higher NGAL levels were detected in the group
      not receiving theophylline (p = 0.025). After 5 days of cisplatin administration,
      urine protein levels were significantly higher in both groups (p < 0.001).
      CONCLUSION: Results showed that urine NGAL level is a superior biomarker compared
      to serum creatinine and serum cystatin C in the detection of early AKI.
      Theophylline was found not to bring a complete protection for the kidneys, but
      less nephrotoxicity was developed when compared to the group not receiving
      theophylline.

PMID- 27049177
TI  - Development of Small Molecules that Specifically Inhibit the D-loop Activity of
      RAD51.
AB  - RAD51 is the central protein in homologous recombination (HR) DNA repair and
      represents a therapeutic target in oncology. Herein we report a novel class of
      RAD51 inhibitors that were identified by high throughput screening. In contrast
      to many previously reported RAD51 inhibitors, our lead compound 1 is capable of
      blocking RAD51-mediated D-loop formation (IC50 21.3 +/- 7.8 MUM) at
      concentrations that do not influence RAD51 binding to ssDNA. In human cells, 1
      inhibits HR (IC50 13.1 +/- 1.6 MUM) without blocking RAD51's ability to assemble
      into subnuclear foci at sites of DNA damage. We determined that the active
      constituent of 1 is actually an oxidized derivative (termed RI(dl)-1 or 8) of the
      original screening compound. Our SAR campaign also yielded RI(dl)-2 (hereafter
      termed 9h), which effectively blocks RAD51's D-loop activity in biochemical
      systems (IC50 11.1 +/- 1.3 MUM) and inhibits HR activity in human cells (IC50 3.0
      +/- 1.8 MUM).

PMID- 27049178
TI  - Ultra-widefield fundus autofluorescence patterns in retinitis pigmentosa and
      other retinal dystrophies.

PMID- 27049179
TI  - Surgical Exposure Trends and Controversies in Extremity Fracture Care.
AB  - Surgical exposures for the management of extremity fractures continue to evolve.
      Strategies to achieve satisfactory articular reconstitution require surgeons to
      have an appreciation and understanding of various conventional and contemporary
      surgical approaches. The recent literature has witnessed a surge in studies on
      surgical approaches for the fixation of extremity fractures. This increased
      interest in surgical exposures resulted from not only a desire to enhance
      outcomes and minimize complications but also a recognition of the inadequacies of
      traditionally accepted surgical exposures. Contemporary exposures may be
      modifications or combinations of existing exposures. All surgical exposures
      require proper surgical execution and familiarity with regional anatomic
      structures. Exposures, whether conventional or contemporary, must provide
      sufficient access for reduction and implant insertion. Proper exposure selection
      can greatly enhance a surgeon's ability to achieve acceptable reduction and
      adequate fixation. Unique characteristics of both the patient and his or her
      fracture pathoanatomy may dictate the surgical approach. Patient positioning,
      imaging access, and concomitant comorbidities (medical, systemic trauma, and
      regional extremity related) also must be considered. Minimally invasive methods
      of reduction and fixation are attractive and have merit; however, adherence to
      them while failing to achieve satisfactory reduction and fixation will not
      generate a desirable outcome. Surgeons should be aware of several site-specific
      anatomic regions in which evolving surgical exposures and strategies for
      extremity fracture management have had favorable outcomes. 

PMID- 27049180
TI  - Lower Extremity Fracture Reduction: Tips, Tricks, and Techniques So That You
      Leave the Operating Room Satisfied.
AB  - It can be challenging for surgeons to obtain proper alignment and to create
      stable constructs for the maintenance of many lower extremity fractures until
      union is achieved. Whether lower extremity fractures are treated with plates and
      screws or intramedullary nails, there are numerous pearls that may help surgeons
      deal with these difficult injuries. Various intraoperative techniques can be used
      for lower extremity fracture reduction and stabilization. The use of several
      reduction tools, tips, and tricks may facilitate the care of lower extremity
      fractures and, subsequently, improve patient outcomes. 

PMID- 27049181
TI  - Fractures and Dislocations About the Elbow and Their Adverse Sequelae:
      Contemporary Perspectives.
AB  - Fractures and dislocations of the elbow can result in adverse outcomes. The elbow
      is a unique joint that allows for great mobility but is predisposed to
      instability, either simple or complex, in traumatic settings. Even simple elbow
      instability, in which no fracture is present, may be associated with tremendous
      soft-tissue injury. Surgical treatment is often required for complex instability
      in which various fractures are present. The treatment goals for fixation of elbow
      fractures and dislocations include stable fracture fixation, a stable
      concentrically reduced joint, and early range of motion. Continued pain,
      stiffness, and instability as well as heterotopic ossification are common
      sequelae of elbow fractures and dislocations. 

PMID- 27049182
TI  - The Unstable Elbow: Current Concepts in Diagnosis and Treatment.
AB  - Elbow instability is common and may occur after a variety of injuries, including
      falls or direct blows. Instability can be classified as either acute or chronic.
      Acute instability is classified as simple (without fracture) or complex (with
      associated fracture). Chronic instability is classified as a chronically
      dislocated or recurrently unstable elbow. Recurrent instability commonly presents
      as isolated medial or lateral collateral ligament insufficiency. A chronically
      dislocated elbow is often more complex, involving both osseous and ligamentous
      injuries. The treatment of simple dislocations typically involves closed
      reduction and nonsurgical management. Chronic recurrent lateral and medial
      collateral ligament insufficiencies have very different clinical characteristics,
      but definitive treatment frequently involves ligament reconstruction. Complex
      instability usually requires surgery, which includes open reduction and internal
      fixation of coronoid and olecranon fractures, repair or replacement of radial
      head fractures, and lateral collateral ligament repair. Medial collateral
      ligament repair and/or external fixation are rarely required to restore
      stability. It is important for surgeons to understand current concepts in the
      diagnosis and management of acute and chronic elbow instability as well as the
      preferred surgical treatments and techniques for the management of these
      injuries. 

PMID- 27049183
TI  - Arthroscopic Rotator Cuff Repair: Indication and Technique.
AB  - Shoulder arthroscopy and rotator cuff repair techniques are frequently used by
      most practicing orthopaedic surgeons. A thorough patient history and physical
      examination can often confirm the presence of a rotator cuff tear, and imaging
      can be used to evaluate the extent of the injury. The indication for rotator cuff
      repair is a painful shoulder refractory to nonsurgical management. Arthroscopic
      techniques, including capsular and coracohumeral ligament releases to decrease
      tension on the repair, facilitate successful rotator cuff repair.
      Biomechanically, a double-row transosseous-equivalent rotator cuff repair
      provides excellent results for medium-size rotator cuff tears. Larger, retracted
      rotator cuff tears may be better repaired with oblique convergence sutures and a
      medial single-row rotator cuff repair. The biology of healing, the preservation
      of blood supply, and the trephination of the bony healing bed are essential parts
      of all rotator cuff repair procedures. Protection of the rotator cuff repair with
      an abduction sling for 4 to 8 weeks postoperatively and the delay of active
      motion until early healing has occurred will improve outcomes. 

PMID- 27049184
TI  - Challenges and Controversies in Treating Massive Rotator Cuff Tears.
AB  - Massive rotator cuff tears present several challenges for orthopaedic surgeons.
      Many rotator cuff tears can be repaired; however, some chronic rotator cuff tears
      require advanced reconstructive techniques. Repair, if possible, is the optimal
      treatment for rotator cuff tears. In general, muscle transfers are an option for
      patients younger than 60 years who do not have pseudoparalysis. Arthroplasty is
      an option for older patients who have concomitant arthritis and for patients who
      have pseudoparalysis. Biologic augmentation in the setting of rotator cuff tears
      continues to evolve, and the application of biologic products should be guided by
      sound evidence and cost-benefit considerations. 

PMID- 27049185
TI  - Shoulder Arthroplasty: Key Steps to Improve Outcomes and Minimize Complications.
AB  - Advances in shoulder replacement surgery have allowed for the successful
      treatment of various shoulder conditions. As the elderly population increases and
      the surgical indications for shoulder replacement surgery continue to expand, the
      number of shoulder replacements performed annually will continue to increase.
      Accordingly, the number of complications also will be expected to increase.
      Successful shoulder replacement outcomes require surgeons to have a thorough
      understanding of the surgical indications, surgical technique, and potential
      complications of the procedure. By reviewing the key aspects of shoulder
      replacement surgery and focusing on the surgical technique and common
      complications for both anatomic and reverse total shoulder arthroplasty, surgeons
      can help improve outcomes and minimize complications. 

PMID- 27049186
TI  - Biomechanics of Reverse Shoulder Arthroplasty: ?Current Concepts.
AB  - The evolution of reverse shoulder arthroplasty has provided surgeons with new
      solutions for many complex shoulder problems. A primary goal of orthopaedics is
      the restoration or re-creation of functional anatomy to reduce pain and improve
      function, which can be accomplished by either repairing injured structures or
      replacing them as anatomically as possible. If reconstructible tissue is lacking
      or not available, which is seen in patients who have complex shoulder conditions
      such as an irreparable rotator cuff-deficient shoulder, cuff tear arthropathy, or
      severe glenoid bone loss, substantial problems may arise. Historically,
      hemiarthroplasty or glenoid grafting with total shoulder arthroplasty yielded
      inconsistent and unsatisfactory results. Underlying pathologies in patients who
      have an irreparable rotator cuff-deficient shoulder, cuff tear arthropathy, or
      severe glenoid bone loss can considerably alter the mechanical function of the
      shoulder and create treatment dilemmas that are difficult to overcome. A better
      biomechanical understanding of these pathologic adaptations has improved
      treatment options. In the past three decades, reverse total shoulder arthroplasty
      was developed to treat these complex shoulder conditions not by specifically re
      creating the anatomy but by using the remaining functional tissue to improve
      shoulder balance. Reverse total shoulder arthroplasty has achieved reliable
      improvements in both pain and function. Initial implant designs lacked scientific
      evidence to support the design rationale, and many implants failed because
      surgeons did not completely understand the forces involved or the pathology being
      treated. Implant function and clinical results will continue to improve as
      surgeons' biomechanical understanding of shoulder disease and reverse shoulder
      arthroplasty implants increases. 

PMID- 27049187
TI  - Scapular Notching.
AB  - Developed in 1985, the Grammont-style reverse total shoulder arthroplasty offered
      a biomechanical advantage for the deltoid muscle as well as predictably reduced
      pain and improved shoulder function in rotator cuff-deficient shoulders. Despite
      favorable outcomes, reverse total shoulder arthroplasty is associated with a
      unique set of complications, one of which is scapular notching. Scapular notching
      is believed to be a result of mechanical impingement of the humeral component on
      the lateral scapular pillar. Although it appears that scapular notching
      progresses with time, its effect on implant survivorship and clinical outcomes is
      unknown. Factors associated with scapular notching are categorized into several
      groups, including patient-specific risk factors, surgical approach and technique,
      and prosthetic design. Surgical strategies to reduce the rate of scapular
      notching include inferior positioning of the glenosphere, inferior tilting of the
      glenosphere, and increasing the size of the glenosphere. A lateralized center of
      rotation and a decreased humeral shaft-neck angle also decrease the incidence of
      scapular notching. As the indications for reverse total shoulder arthroplasty
      expand, it is important for orthopaedic surgeons to understand the etiology and
      incidence, predictive factors, and clinical relevance of scapular notching as
      well as strategies to avoid it. 

PMID- 27049188
TI  - Emerging Indications for Reverse Shoulder Arthroplasty.
AB  - Historically, reverse shoulder arthroplasty was reserved for older, low-demand
      patients in whom rotator cuff arthropathy was diagnosed. Other common indications
      included sequelae of previously treated proximal humerus fractures, failed
      anatomic total shoulder arthroplasty, tumor resection, and rheumatoid arthritis
      in the elderly population. Unpredictable implant durability and high complication
      rates have limited the use of reverse shoulder arthroplasty to a narrow group of
      patients. Over the past decade, however, research has led to an improved
      understanding of the biomechanics behind reverse shoulder prostheses, which has
      improved implant design and surgical techniques. Consequently, orthopaedic
      surgeons have slowly begun to expand the indications for reverse shoulder
      arthroplasty to include a wider spectrum of shoulder pathologies. Recent studies
      have shown promising results for patients who undergo reverse shoulder
      arthroplasty for the treatment of acute proximal humerus fractures, massive
      rotator cuff tears without arthropathy, primary osteoarthritis, and chronic
      anterior dislocation, as well as for younger patients who have rheumatoid
      arthritis. These data suggest that, with judicious patient selection, reverse
      shoulder arthroplasty can be an excellent treatment option for a growing patient
      cohort. 

PMID- 27049189
TI  - Reverse Shoulder Arthroplasty for Trauma: When, Where, and How.
AB  - Reverse shoulder arthroplasty has become increasingly popular for the treatment
      of complex shoulder injuries, including proximal humerus fractures and fixed
      glenohumeral dislocation, in the elderly population. The early to midterm results
      of reverse shoulder arthroplasty for the treatment of proximal humerus fractures
      are promising compared with the results of unconstrained humeral head
      replacement, and patients may have more predictable improvement with less
      dependence on bone healing and rehabilitation. However, long-term follow-up is
      needed, and surgeons must be familiar with various complications that are
      specific to reverse shoulder arthroplasty. To achieve optimal patient outcomes
      for the management of traumatic shoulder injuries, surgeons must have a
      comprehensive understanding of the current implant options, indications, and
      surgical techniques for reverse shoulder arthroplasty. 

PMID- 27049190
TI  - All Things Clavicle: From Acromioclavicular to Sternoclavicular and All Points in
      Between.
AB  - The clavicle is the most frequently injured bone in the human body. In most
      cases, fractures that occur in the midshaft of the clavicle can be managed
      nonsurgically. An increasing number of studies suggest that displaced midshaft
      clavicle fractures have improved outcomes after surgical management, and
      equivalent outcomes can be achieved with both plating and intramedullary
      techniques. Distal clavicle fractures are managed according to the disruption of
      the coracoclavicular ligaments. Fractures with disruption of the ligaments
      usually will require fixation, whereas fractures with intact ligaments may be
      treated with closed management. Multiple techniques of reconstruction appear to
      yield similar outcomes; however, hook-plating techniques result in the highest
      complication rates. The evaluation process for acromioclavicular joint injuries
      is moving from a static two-dimensional evaluation to a three-dimensional
      evaluation that involves an assessment for scapular dyskinesis. Surgical
      reconstruction is indicated for patients who exhibit scapular dyskinesis.
      Anterior sternoclavicular injuries can typically be managed nonsurgically,
      whereas posterior sternoclavicular dislocations always require urgent surgical
      management. Newer techniques of ligament reconstruction for sternoclavicular
      injuries yield improved biomechanical stability. 

PMID- 27049191
TI  - Preventing Hospital Readmissions and Limiting the Complications Associated With
      Total Joint Arthroplasty.
AB  - Total joint arthroplasty is a highly successful surgical procedure for patients
      who have painful arthritic joints. The increasing prevalence of total joint
      arthroplasty is generating substantial expenditures in the American healthcare
      system. Healthcare payers, specifically the Centers for Medicare and Medicaid
      Services, currently target total joint arthroplasty as an area for healthcare
      cost-savings initiatives, which has resulted in increased scrutiny surrounding
      orthopaedic care, health resource utilization, and hospital readmissions.
      Identifying the complications associated with total hip and total knee
      arthroplasty that result in readmissions will be critically important for
      predictive modeling and to decrease the number of readmissions after total joint
      arthroplasty. In addition, improving perioperative optimization, providing
      seamless episodic care, and intensifying posthospital coordination of care may
      decrease the number of unnecessary hospital readmissions. Identified modifiable
      risk factors that substantially contribute to poor clinical outcomes after total
      joint arthroplasty include morbid obesity; poorly controlled diabetes and
      nutritional deficiencies; Staphylococcus aureus colonization; tobacco use; venous
      thromboembolic disease; cardiovascular disease; neurocognitive, psychological,
      and behavioral problems; and physical deconditioning and fall risk. Both clinical
      practice and research will be enhanced if defined total joint arthroplasty
      complications are standardized and stratification schemes are used to identify
      high-risk patients. Subsequently, clinical intervention will be warranted to
      address modifiable risk factors before proceeding with total joint arthroplasty. 

PMID- 27049192
TI  - Contemporary Strategies for Rapid Recovery Total Hip Arthroplasty.
AB  - Over the past several years, rapid recovery protocols for total hip arthroplasty
      have evolved in parallel with advancements in pain management, regional
      anesthesia, focused rehabilitation, and the patient selection process. As fiscal
      pressures from payers of health care increase, surgical outcomes and
      complications are being scrutinized, which evokes a sense of urgency for
      arthroplasty surgeons as well as hospitals. The implementation of successful
      accelerated recovery pathways for total hip arthroplasty requires the coordinated
      efforts of surgeons, practice administrators, anesthesiologists, nurses, physical
      and occupational therapists, case managers, and postacute care providers. To
      optimize performance outcomes, it is important for surgeons to select patients
      who are eligible for rapid recovery. The fundamental tenets of multimodal pain
      control, regional anesthesia, prudent perioperative blood management, venous
      thromboembolic prophylaxis, and early ambulation and mobility should be
      collectively addressed for all patients who undergo primary total hip
      replacement. 

PMID- 27049193
TI  - Preventing Leg Length Discrepancy and Instability After Total Hip Arthroplasty.
AB  - Restoration of equal leg lengths and dynamic hip stability are essential elements
      of a successful total hip arthroplasty. A careful clinical examination, a
      preoperative plan, and appropriate intraoperative techniques are necessary to
      achieve these goals. Preoperative identification of patients at risk for residual
      leg length discrepancy allows surgeons to adjust the surgical approach and/or the
      type of implant and provide better preoperative patient education. The use of
      larger femoral heads, high-offset stem options, and enhanced soft-tissue repairs
      have improved impingement-free range of motion as well as dynamic hip stability
      and have contributed to an overall reduction in dislocation. Methods for accurate
      leg length restoration and component positioning include anatomic landmarks,
      intraoperative radiographs, intraoperative calipers, stability testing, and
      computer-assisted surgery. If recurrent instability occurs after total hip
      arthroplasty, the underlying cause for dislocation should be identified and
      treated; this may include the use of semiconstrained dual-mobility or fully
      constrained liners, depending on abductor function. Surgeons should be aware of
      the clinical and surgical techniques for achieving leg length equalization and
      dynamic hip stability in total hip arthroplasty. 

PMID- 27049194
TI  - The Difficult Primary Total Knee Arthroplasty.
AB  - Primary total knee arthroplasty (TKA) for the treatment of knee arthritis has
      substantially increased over the past decade. Because of its success, the
      indications for primary TKA have expanded to include younger patients who are
      more active, elderly patients who have multiple comorbidities, and patients who
      have more complex issues, such as posttraumatic arthritis and severe deformity.
      TKA also has been used to salvage failed unicondylar arthroplasty and osteotomies
      about the knee. Exposure may be challenging and outcomes may not be as successful
      in patients with soft-tissue contractures, such as a stiff knee, who undergo TKA.
      Bone graft or augments may be required to correct deformity and attain proper
      knee alignment in patients who have a substantial varus or valgus deformity. TKA
      is somewhat challenging in patients who have deformity, bone loss, contracture,
      or multiple comorbidities, or have had prior surgery; therefore, it is necessary
      for surgeons to be aware of some general principles that may help minimize
      complications and improve outcomes. 

PMID- 27049195
TI  - Treating the Aging Spine.
AB  - Demographic trends make it incumbent on orthopaedic spine surgeons to recognize
      the special challenges involved in caring for older patients with spine
      pathology. Unique pathologies, such as osteoporosis and degenerative deformities,
      must be recognized and treated. Recent treatment options and recommendations for
      the medical optimization of bone health include vitamin D and calcium
      supplementation, diphosphonates, and teriparatide. Optimizing spinal fixation in
      elderly patients who have osteoporosis is critical; cement augmentation of
      pedicle screws is promising. In the management of geriatric odontoid fractures,
      nonsurgical support with a collar may be considered for low-demand patients,
      whereas surgical fixation is favored for high-demand patients. Management of
      degenerative deformity must address sagittal plane balance, which includes
      consideration of pelvic incidence. Various osteotomies may prove helpful in this
      setting. 

PMID- 27049196
TI  - Avoiding and Managing Intraoperative Complications During Cervical Spine Surgery.
AB  - The incidence of intraoperative complications during cervical spine surgery is
      low; however, if they do occur, intraoperative complications have the potential
      to cause considerable morbidity and mortality. Spine surgeons should be familiar
      with methods to minimize intraoperative complications. If they do occur, surgeons
      must be prepared to immediately treat each potential complication to reduce any
      associated morbidity. 

PMID- 27049197
TI  - Collateral Adverse Outcomes After Lumbar Spine Surgery.
AB  - Collateral adverse outcomes are the expected or unavoidable results of a
      procedure that is performed in a standard manner and typically experienced by the
      patient. Collateral adverse outcomes do not result from errors, nor are they
      rare. Collateral adverse outcomes occur as the direct result of a surgical
      procedure and must be accepted as a trade-off to attain the intended benefits of
      the surgical procedure. As such, collateral adverse outcomes do not fit into the
      traditional definition of a complication or adverse event. Examples of collateral
      adverse outcomes after lumbar spine arthrodesis include lumbar stiffness,
      postoperative psychological stress, postoperative pain, peri-incisional numbness,
      paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a
      comparison of interventions for the treatment of a clinical condition should
      include information on both the negative consequences (expected and unexpected)
      and potential benefits of the treatment options. The objective evaluation and
      reporting of collateral adverse outcomes will provide surgeons with a more
      complete picture of invasive interventions and, thus, the improved ability to
      assess alternative treatment options. 

PMID- 27049198
TI  - Role of Fresh Osteochondral Allografts for Large Talar Osteochondral Lesions.
AB  - Osteochondral lesions of the talus, large or small, are challenging for the
      treating orthopaedic surgeon. These cartilage and bony defects can cause
      substantial pain and functional disability. Surgical treatment of small
      osteochondral lesions of the talus has been thoroughly explored and includes
      retrograde drilling, arthroscopic debridement and marrow stimulation,
      osteochondral autografting from cartilage/bone unit harvested from the
      ipsilateral knee (mosaicplasty), and autologous chondrocyte implantation.
      Although each of these reparative, replacement, or regenerative techniques has
      varying degrees of success, they may be insufficient for the treatment of large
      osteochondral lesions of the talus. Large-volume osteochondral lesions of the
      talus (>1.5 cm in diameter or >150 mm(2) in area) often involve a sizable portion
      of the weight-bearing section of the talar dome, medially or laterally. A fresh
      structural osteochondral allograft is a viable treatment option for large
      osteochondral lesions of the talus. 

PMID- 27049199
TI  - Outcomes of Ankle Distraction for the Treatment of Ankle Arthritis.
AB  - Ankle arthrodesis and total ankle arthroplasty are the most common treatments for
      end-stage ankle osteoarthritis; however, these surgeries are not ideal for young,
      active patients because of the nature and long-term consequences of sacrificing
      the ankle joint. The concept of joint distraction was introduced in the 1970s but
      has only received clinical support in the past two decades as interest in joint
      preservation treatments has grown. Ankle distraction preserves the native joint
      and, thus, does not compromise any future arthroplasty or arthrodesis, if
      required. The main indication for ankle distraction is severe osteoarthritis,
      and, with encouraging data, the indications continue to expand. The early results
      of ankle distraction are promising; however, ankle function after joint
      distraction declines over time. Careful patient selection is necessary to
      optimize ankle distraction outcomes and avoid complications. 

PMID- 27049200
TI  - Ankle Arthritis: You Can't Always Replace It.
AB  - End-stage arthritis of the tibiotalar joint is disabling and causes substantial
      functional impairment. End-stage arthritis of the tibiotalar joint is often the
      residual effect of a previous traumatic injury. Nonsurgical treatment for end
      stage arthritis of the ankle includes bracing, shoe wear modifications, and
      selective joint injections. For patients who fail to respond to nonsurgical
      modalities, the two primary treatment options are arthroplasty and arthrodesis.
      Each treatment option has strong proponents who argue the superiority of their
      treatment algorithm. Although there is no ideal treatment for ankle arthritis,
      there are high-quality studies that help guide treatment in patients of varying
      demographics. Many inherent risks are linked with each treatment option; however,
      the risks of greatest concern are early implant loosening after arthroplasty that
      requires revision surgery and the acceleration of adjacent joint degeneration
      associated with arthrodesis. 

PMID- 27049201
TI  - The Failed Cavovarus Foot: What Went Wrong and Why?
AB  - The adult cavovarus foot exists on a spectrum and, therefore, requires a thorough
      evaluation to determine the extent of the deformity and then choose from a
      multitude of surgical procedures to achieve correction. Regardless of the
      severity of the deformity, treatment should include an algorithmic approach to
      adequately achieve a stable, balanced, and plantigrade foot. To prevent failure,
      the surgeon should evaluate whether the deformity is flexible or rigid, determine
      the location of the apex or apices of the deformity, evaluate any muscle
      imbalances occurring about the foot and ankle, and determine the need for
      additional procedures. A failure to consider these principles and, subsequently,
      the extent of the deformity often results in recurrence and progression of the
      deformity. 

PMID- 27049202
TI  - Avoiding Errors in the Management of Pediatric Polytrauma Patients.
AB  - Management of pediatric polytrauma patients is one of the most difficult
      challenges for orthopaedic surgeons. Multisystem injuries frequently include
      complex orthopaedic surgical problems that require intervention. The physiology
      and anatomy of children and adolescent trauma patients differ from the physiology
      and anatomy of an adult trauma patient, which alters the types of injuries
      sustained and the ideal methods for management. Errors of pediatric polytrauma
      care are included in two broad categories: missed injuries and inadequate
      fracture treatment. Diagnoses may be missed most frequently because of a
      surgeon's inability to reliably assess patients who have traumatic brain injuries
      and painful distracting injuries. Cervical spine injuries are particularly
      difficult to identify in a child with polytrauma and may have devastating
      consequences. In children who have multiple injuries, the stabilization of long
      bone fractures with pediatric fixation techniques, such as elastic nails and
      other implants, allows for easier care and more rapid mobilization compared with
      cast treatments. Adolescent polytrauma patients who are approaching skeletal
      maturity, however, are ideally treated as adults to avoid complications, such as
      loss of fixation, and to speed rehabilitation. 

PMID- 27049203
TI  - Current Strategies for the Management of Pediatric Supracondylar Humerus
      Fractures: Tips and Techniques for Successful Closed Treatment.
AB  - Pediatric supracondylar humerus fractures are the most commonly encountered type
      of elbow fractures in children that require surgical fixation. Many pediatric
      supracondylar humerus fractures can be treated with closed reduction and
      percutaneous skeletal fixation. In difficult fractures, adjunct pin techniques,
      such as joystick wires and leverage pins, can be used to help attain a
      satisfactory and stable reduction before an open approach is used. After the
      fracture is reduced, optimal pinning, with the use of either crossed or lateral
      entry techniques, and fixation that achieves maximal spread at the fracture site
      as well as bicortical engagement in both fragments are essential to maintain
      reduction and avoid complications that are associated with malunion. A practical
      approach as well as several tips and techniques may help surgeons attain and
      maintain stable closed reduction of pediatric supracondylar humerus fractures. 

PMID- 27049204
TI  - Open Reduction Techniques for Supracondylar Humerus Fractures in Children.
AB  - Supracondylar humerus fractures are the most common elbow fractures in children.
      Displaced supracondylar humerus fractures that are associated with neurologic
      and/or vascular injuries should be treated with timely reduction via closed
      techniques. If closed reduction fails, reduction via open techniques is
      indicated. There is controversy about which surgical approach yields the best
      cosmetic and functional outcomes while minimizing postoperative complications.
      Open reduction, if indicated, has been reported to yield good outcomes in
      patients in whom closed reduction fails. 

PMID- 27049205
TI  - The Difficult Supracondylar Humerus Fracture: Flexion-Type Injuries.
AB  - Although flexion-type supracondylar humerus fractures account for a minority of
      all supracondylar humerus fractures, they warrant special attention because of
      their relatively high rate of requirement for open reduction and their potential
      for ulnar nerve injury or entrapment. The severity of flexion-type supracondylar
      humerus fractures may be difficult to appreciate on initial radiographs;
      therefore, surgeons must have a high index of suspicion in the evaluation of a
      patient who has a suspected flexion-type supracondylar humerus fracture.
      Nondisplaced or minimally displaced flexion-type supracondylar humerus fractures
      can be treated with long arm casting. Displaced flexion-type supracondylar
      humerus fractures require surgical reduction and stabilization. The unique
      instability of and reduction position for flexion-type supracondylar humerus
      fractures make reduction and pinning more of a challenge compared with the more
      common extension-type supracondylar humerus fractures; therefore, special
      considerations are required in the surgical setup and planning for flexion-type
      supracondylar humerus fractures. 

PMID- 27049206
TI  - Transphyseal Distal Humerus Fracture.
AB  - Transphyseal distal humerus fractures typically occur in children younger than 3
      years secondary to birth trauma, nonaccidental trauma, or a fall from a small
      height. Prompt and accurate diagnosis of a transphyseal distal humerus fracture
      is crucial for a successful outcome. Recognizing that the forearm is not aligned
      with the humerus on plain radiographs may aid in the diagnosis of a transphyseal
      distal humerus fracture. Surgical management is most commonly performed with the
      aid of an arthrogram. Closed reduction and percutaneous pinning techniques
      similar to those used for supracondylar humerus fractures are employed. Cubitus
      varus caused by a malunion, osteonecrosis of the medial condyle, or growth arrest
      is the most common complication encountered in the treatment of transphyseal
      distal humerus fractures. A corrective lateral closing wedge osteotomy can be
      performed to restore a nearly normal carrying angle. 

PMID- 27049207
TI  - Common Errors in the Management of Pediatric Supracondylar Humerus Fractures and
      Lateral Condyle Fractures.
AB  - Supracondylar humerus fractures and lateral condyle fractures are the two most
      common pediatric elbow fractures that require surgical intervention. Although
      most surgeons are familiar with supracondylar humerus fractures and lateral
      condyle fractures, these injuries present challenges that may lead to common
      errors in evaluation and management and, thus, compromise outcomes. It is well
      agreed upon that nondisplaced supracondylar fractures (Gartland type I) are best
      managed nonsurgically with cast immobilization. Errors may be made, however, in
      the treatment of type II fractures because the extent of displacement and
      instability are difficult to assess. Although some type II fractures are stable
      after closed reduction, many are not and benefit from closed reduction and
      percutaneous pinning to prevent late displacement and cubitus varus deformity.
      Stable fixation must be achieved and errors related to pin placement must be
      avoided to prevent the failure of type III fractures after closed reduction and
      percutaneous pinning. Many potential errors and pitfalls also are seen in the
      management of lateral condyle fractures. Radiographic assessment of displacement
      can be improved by obtaining an internal oblique view of the elbow. Surgical
      treatment with closed reduction and percutaneous pinning may be indicated for
      minimally displaced fractures (2 to 4 mm) that show evidence of increasing
      displacement over time or demonstrate intra-articular extension on an arthrogram.
      Displaced fractures are best treated with open reduction and internal fixation.
      Errors in surgical dissection, fracture reduction, and fixation are common and
      may result in osteonecrosis, malunion, and nonunion. 

PMID- 27049208
TI  - Pediatric Monteggia Fracture-Dislocations: Avoiding Problems and Managing
      Complications.
AB  - Monteggia fracture-dislocations typically involve a dislocation of the radial
      head with an associated fracture of the ulnar shaft. The prompt diagnosis and
      treatment of these acute injuries result in excellent outcomes. Unfortunately, a
      Monteggia fracture-dislocation is often missed during diagnostic testing and
      results in a chronic Monteggia fracture-dislocation. The subsequent timing and
      treatment of chronic Monteggia fracture-dislocations are debatable because
      outcomes are suboptimal. Therefore, it is critical that the initial injury be
      correctly diagnosed and treated as close to the time of injury as possible to
      ensure excellent outcomes. 

PMID- 27049209
TI  - Arthroscopic Management of Anterior, Posterior, and Multidirectional Shoulder
      Instabilities.
AB  - Arthroscopic shoulder stabilization offers several potential advantages compared
      with open surgery, including the opportunity to more accurately evaluate the
      glenohumeral joint at the time of diagnostic assessment; comprehensively address
      multiple pathologic lesions that may be identified; and avoid potential
      complications unique to open stabilization, such as postoperative subscapularis
      failure. A thorough understanding of normal shoulder anatomy and biomechanics,
      along with the pathoanatomy responsible for anterior, posterior, and
      multidirectional shoulder instability patterns, is very important in the
      management of patients who have shoulder instability. The treating physician also
      must be familiar with diagnostic imaging and physical examination maneuvers that
      are required to accurately diagnose shoulder instability. 

PMID- 27049210
TI  - Hip Arthroscopy: Tales From the Crypt.
AB  - Complications after hip arthroscopy vary in frequency and severity, even for
      experienced surgeons. It is important for surgeons to be aware of some of the
      more dramatic, often unusual, and always memorable (nightmarish) complications of
      hip arthroscopy and understand how they are caused, how they can be treated, and
      how they can be prevented. 

PMID- 27049211
TI  - Update on Biomaterials.
AB  - Biomaterials are essential to the use and development of successful treatments
      for orthopaedic patients. Orthopaedic surgeons need to understand the expected
      clinical performance and the effects of implants in patients. Recent attempts to
      improve implant durability have resulted in adverse effects related to
      biomaterials and their relationship to patients. Examples of these adverse
      effects in hip arthroplasty include wear and corrosion of metal-on-metal
      bearings, trunnions, and tapered modular neck junctions. Conversely, polymers and
      ceramics have shown substantial improvements in durability. Improved implant
      compositions and manufacturing processes have resulted in ceramic head and
      acetabular liners with improved material properties and the avoidance of voids,
      which have, in the past, caused catastrophic fractures. Cross-linking of
      polyethylene with radiation and doping with antioxidants has substantially
      increased implant durability and is increasingly being used in joint prostheses
      other than the hip. Additive manufacturing is potentially a transformative
      process; it can lead to custom and patient-specific implants and to improvements
      in material properties, which can be optimized to achieve desired bone responses.
      Orthopaedic surgeons must understand the material properties and the biologic
      effects of new or altered biomaterials and manufacturing processes before use. In
      addition, a clear benefit to the patient must be proven based on superior
      preclinical results and high-quality clinical investigations before orthopaedic
      surgeons use new or altered biomaterials. 

PMID- 27049212
TI  - Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current
      Concepts.
AB  - Infection is a rare, serious complication after total joint arthroplasty and
      constitutes a considerable emotional and financial burden for patients, surgeons,
      and healthcare systems. Prevention of surgical site and periprosthetic joint
      infections is crucial. This requires knowledge of the microorganisms that
      commonly cause these infections, including Staphylococcus species. Selection of
      the appropriate antibiotic regimen to treat infection remains controversial, but
      cefazolin and cefuroxime are the most commonly recommended antibiotics for
      prophylaxis. Appropriate timing of administration before surgery, with redosing
      performed as needed, can help to ensure optimal antibiotic concentration during
      surgery. Given the increasing evidence that S aureus colonization is a risk
      factor for periprosthetic joint infection, an exploration of the potential
      benefits of preoperative S aureus carrier screening and decolonization protocols
      is warranted. The use of antibiotic-loaded bone cement in primary total joint
      arthroplasty and antibiotic powder at wound closure are other controversial
      topics that require additional research. 

PMID- 27049213
TI  - Cardiovascular Considerations for Joint Replacement Surgery.
AB  - Heart disease is the leading cause of death in the United States. Cardiovascular
      complications are associated with higher morbidity and mortality rates for
      patients who undergo orthopaedic surgery. Therefore, the clinical importance of a
      comprehensive preoperative evaluation and medical clearance is crucial and may
      substantially improve postoperative outcomes. A thorough knowledge of
      cardiovascular perioperative planning and management can enable healthcare
      professionals to identify patients who are potentially at risk for cardiovascular
      complications, and eventually improve both short- and long-term patient outcomes
      and satisfaction. 

PMID- 27049214
TI  - Renal and Gastrointestinal Considerations in Patients Undergoing Elective
      Orthopaedic Surgery.
AB  - To minimize perioperative complications after elective orthopaedic procedures,
      patients may undergo preoperative medical optimization, which includes an
      assessment of their renal function and gastrointestinal system. The
      gastrointestinal and renal systems are complex, and their proper optimization in
      the preoperative period can influence the success of any procedure. Several
      factors, including a thorough evaluation and screening, with particular emphasis
      on anemia and its renal and gastrointestinal causes; the management of
      medications that are metabolized by the liver and excreted by the kidneys; and
      careful attention to the patient's nutritional status, can prevent complications
      and reduce morbidity, mortality, and the cost of care after elective orthopaedic
      procedures. 

PMID- 27049215
TI  - Perioperative Treatment of Patients with Rheumatoid Arthritis.
AB  - Rheumatoid arthritis is an autoimmune disease mediated by a widespread, chronic,
      and systematic inflammatory process that causes joint deterioration, which leads
      to pain, disability, and poor quality of life. The increased use of disease
      modifying antirheumatic drugs has been shown to markedly slow disease
      progression, which has translated into a decrease in the need for orthopaedic
      intervention in this population. However, in a substantial percentage of patients
      with the disease, optimal pharmacologic treatment fails and surgical intervention
      is required. A thorough understanding of medical considerations in these patients
      and improved knowledge of the medical complications caused by the disease process
      and the pharmacologic therapy used to treat it may lead to improved preoperative
      planning and medical clearance, which may ultimately improve the overall
      postoperative outcome. 

PMID- 27049216
TI  - Effect of Smoking on Joint Replacement Outcomes: Opportunities for Improvement
      Through Preoperative Smoking Cessation.
AB  - Because orthopaedic surgeons focus on identifying serious potential
      complications, such as heart attack, stroke, and deep vein thrombosis, during the
      preoperative assessment, correctable factors, such as smoking, may be overlooked.
      Chronic exposure to nicotine has been correlated with perioperative complications
      that lead to worse outcomes, including decreased patient satisfaction, longer
      hospitalization periods, and an increased rate of hospital readmission. It has
      been proven that smoking is a negative risk factor for decreased bone mineral
      density, which leads to increased fracture risk, heightened pain, postoperative
      wound and bone healing complications, decreased fusion rates, and postoperative
      tendon and ligament healing complications. Physician-led preoperative smoking
      cessation programs that include, but are not limited to, pharmacotherapy plans
      have been shown to improve primary surgical outcomes and smoking cessation rates.
      Smoking has detrimental effects on specialty-specific physiology; however, there
      are many effective options for intervention that can improve primary outcomes. 

PMID- 27049217
TI  - Effect of Vitamin D on Joint Replacement Outcomes.
AB  - Vitamin D is a steroid hormone that affects not only bone metabolism and strength
      but also a variety of musculoskeletal health and surgical outcomes that are
      relevant to orthopaedic medicine. Risk factors for vitamin D deficiency include
      sex, age, skin pigmentation, obesity, and preexisting conditions such as
      nephritic syndrome and malabsorption syndrome. Furthermore, vitamin D deficiency
      is associated with the development of postoperative complications, such as an
      increased risk of infection, morbidity, and mortality. The standardization of
      vitamin D terminology as well as a thorough understanding of the medical
      considerations associated with vitamin D deficiency can improve preoperative
      planning and clearance, and, ultimately, patient outcomes and satisfaction. 

PMID- 27049219
TI  - Outpatient Hip and Knee Replacement: The Experience From the First 15 Years.
AB  - Rapid recovery and early discharge after total joint arthroplasty are becoming
      more common. To develop a successful, safe, outpatient arthroplasty practice,
      surgeons must have the support of a multidisciplinary team, which includes an
      orthopaedic surgeon, an anesthesiologist, nurses, physical therapists, and a
      discharge planner. The authors of this chapter recommend surgeons start with
      healthier, motivated patients and focus on total hip replacements and
      unicompartmental knee replacements in the learning curve phase of the transition
      to outpatient total joint arthroplasty. It is important for orthopaedic surgeons
      to establish an outpatient joint arthroplasty protocol as well as ways to avoid
      complications and delays in discharge. 

PMID- 27049218
TI  - Outpatient Arthroplasty is Here Now.
AB  - Substantial advances have been made in arthroplasty to minimize surgical trauma
      and maximize perioperative pain control, which has enabled patients to regain
      mobility within hours of surgical intervention and be safely discharged to home
      the same day. Surgeons should understand the indications and contraindications
      for the safe performance of outpatient arthroplasty in a hospital and ambulatory
      surgical center setting as well as know how to optimize, medically manage,
      prepare, and rehabilitate patients. To undertake outpatient arthroplasty,
      surgeons must be knowledgeable in multimodal anesthesia techniques, effective
      venous thromboembolism prophylaxis, blood management, and wound management. In
      addition, surgeons must learn the subtle nuances of specialized surgical
      techniques that lend themselves to outpatient arthroplasty, including partial
      knee, muscle-sparing total hip, less invasive total knee, and total shoulder
      techniques. 

PMID- 27049220
TI  - Implementation of Bundled Payment Initiatives for Total Joint Arthroplasty:
      Decreasing Cost and Increasing Quality.
AB  - Although the Bundled Payments for Care Improvement (BPCI) Initiative began
      generating data in January 2013, it may be years before the data can determine if
      the BPCI Initiative enhances value without decreasing quality. Private insurers
      have implemented other bundled payment arrangements for the delivery of total
      joint arthroplasty in a variety of practice settings. It is important for
      surgeons to review the early results of the BPCI Initiative and other bundled
      payment arrangements to understand the challenges and benefits of healthcare
      delivery systems with respect to total joint arthroplasty. In addition, surgeons
      should understand methods of cost control and quality improvement to determine
      the effect of the BPCI Initiative on the value-quality equation with respect to
      total joint arthroplasty. 

PMID- 27049221
TI  - Evidence, Quality, Costs, and Reimbursement: ?Connecting the Dots.
AB  - Healthcare costs in the United States continue to rise, and substantial
      variations in the type, quality, and location of that care persist. It is
      critically important for all healthcare stakeholders to address and define value
      in orthopaedic care delivery. Evidence-based orthopaedic care delivery, reliable
      quality and performance measurement, and the delivery of the best care at the
      lowest cost are the key strategies to improve the value of musculoskeletal care.
      A failure to implement these strategies could negatively affect the reimbursement
      of all healthcare providers--at both the private and government payer levels.

PMID- 27049222
TI  - Outcome Measure Development.
AB  - Measuring patient-reported outcomes is the current method for conducting clinical
      research. Creating a new outcome measure is an exhaustive process that should be
      carefully monitored and concentrated on only important and common conditions. The
      evaluation of an existing outcome measure should involve assessing its internal
      consistency, reliability, floor and ceiling effects, validity, and ability to
      measure clinically meaningful change. The most important characteristic of a
      patient-reported outcome is that it is developed with direct input from its
      target patient population. Item generation and reduction is the most critical
      step in the development process because it "guarantees" that patients have
      communicated what is important to them and represents content validity. Outcome
      measures should not change; rather, they should demonstrate responsiveness by
      being reproducible and reliable if a patient's clinical condition is stable or
      reflect differences if a patient's clinical condition varies. Validation is an
      iterative process and requires patients from different settings and
      circumstances. 

PMID- 27049223
TI  - Why Measure Outcomes?
AB  - The concept of measuring the outcomes of treatment in health care was promoted by
      Ernest Amory Codman in the early 1900s, but, until recently, his ideas were
      generally ignored. The forces that have advanced outcome measurement to the
      forefront of health care include the shift in payers for health care from the
      patient to large insurance companies or government agencies, the movement toward
      assessing the care of populations not individuals, and the effort to find value
      (or cost-effective treatments) amid rising healthcare costs. No ideal method
      exists to measure outcomes, and the information gathered depends on the reason
      the outcome information is required. Outcome measures used in research are best
      able to answer research questions. The methods for assessing physician and
      hospital performance include process measures, patient-experience measures,
      structure measures, and measures used to assess the outcomes of treatment. The
      methods used to assess performance should be validated, be reliable, and reflect
      a patient's perception of the treatment results. The healthcare industry must
      measure outcomes to identify which treatments are most effective and provide the
      most benefit to patients. 

PMID- 27049224
TI  - Recommendations for Evaluating and Selecting Appropriately Valued Outcome
      Measures.
AB  - The changing healthcare environment has essentially mandated that outcome scores
      play an increasing role in orthopaedic research and clinical care. Value is
      defined as the best outcome at the lowest cost. The reasoning behind the
      collection of outcome scores can be examined from several perspectives. The
      process of selecting an appropriate outcome measure involves analyzing its
      psychometrics in addition to other aspects, such as responsiveness, reliability,
      validity, and the ability to detect change in a reasonable manner. A minimal
      clinically important difference measures clinical change, and a minimal
      detectable change measures statistical change. Orthopaedic surgeons are most
      interested in minimal clinically important differences because they indicate
      meaningful clinical changes. Guidelines for selecting appropriately valued
      outcome measures include the consideration of patient-reported outcomes, proper
      psychometrics, validated scores, and cost effectiveness. 

PMID- 27049225
TI  - Implementation of a Comprehensive Orthopaedic Registry System.
AB  - Advances in information technology have allowed for improvements in the
      collection and analysis of large-scale outcomes data. These data can be used in
      the practice of orthopaedics for benchmarking, value analysis, and comparative
      effectiveness research. The implementation of registries within a busy surgical
      practice can be challenging, costly, and inefficient. Content, platform, and
      characteristics are the key elements required to successfully implement a patient
      based orthopaedic outcomes data registry. Specific barriers to implementing
      registries are discussed, and solutions are proposed, to provide an example for
      optimal integration within clinical practices that may have varying goals. 

PMID- 27049226
TI  - Practical Quality Improvement Implementation in Orthopaedic Clinical Practice.
AB  - The passage of the Medicare Access and Children's Health Insurance Program
      Reauthorization Act of 2015 (HR 2) helps ensure patient access to care and stable
      physician reimbursement for the near future. HR 2's underlying theme is the
      improvement of value to address the unsustainable rise in national healthcare
      spending. Quality improvement and performance improvement, which affect outcomes
      and costs as well as address variation, are the keys to improve the value of
      orthopaedic healthcare delivery. Orthopaedic surgeons should examine quality and
      performance strategies as well as several examples before they begin to implement
      these processes to improve quality and performance in their practices. 

PMID- 27049227
TI  - Getting Ready for ICD-10 and Meaningful Use Stage 2.
AB  - For the past 24 years, most developed countries have used the International
      Classification of Diseases, Tenth Revision (ICD-10) to report physician services.
      In the United States, physicians have continued to use the American Medical
      Association Current Procedural Terminology, Fourth Edition and the Healthcare
      Common Procedure Coding System. The ICD-10-Clinical Modification (CM) has
      approximately 4.9 times more codes than the International Classification of
      Diseases, Ninth Revision. ICD-10-CM allows for more specific descriptors of a
      procedure and is broken down by category, etiology, anatomic site, severity, and
      extension. ICD-10-CM is scheduled to be implemented by Medicare and commercial
      payers on October 1, 2015. In addition to ICD-10 implementation, physicians have
      to meet the requirements of the Meaningful Use Electronic Health Record Incentive
      Program. The Meaningful Use program is designed to promote the use of certified
      electronic health technology by providing eligible professionals with incentive
      payments if they meet the defined core and menu objectives of each stage of the
      program. All core measures must be met; however, providers can choose to meet a
      preset number of menu measures. Meaningful Use Stage 1 required eligible
      professionals to meet core and menu objectives that focused on data capture and
      sharing. Meaningful Use Stage 2 requires eligible professionals to meet core and
      menu objects that focus on advanced clinical processes for a full year in 2015.
      Stage 3 has been delayed until 2017, and core and menu measures that will focus
      on improving outcomes have not yet been defined. It is important for orthopaedic
      surgeons to understand the history of and techniques for the use of ICD-10-CM in
      clinical practice. Orthopaedic surgeons also should understand the requirements
      for Meaningful Use Stages 1 and 2, including the core objectives that must be met
      to achieve satisfactory attestation. 

PMID- 27049228
TI  - Understanding and Taking Control of Surgical Learning Curves.
AB  - As surgical techniques continue to evolve, surgeons will have to integrate new
      skills into their practice. A learning curve is associated with the integration
      of any new procedure; therefore, it is important for surgeons who are
      incorporating a new technique into their practice to understand what the reported
      learning curve might mean for them and their patients. A learning curve should
      not be perceived as negative because it can indicate progress; however, surgeons
      need to understand how to optimize the learning curve to ensure progress with
      minimal patient risk. It is essential for surgeons who are implementing new
      procedures or skills to define potential learning curves, examine how a reported
      learning curve may relate to an individual surgeon's in-practice learning and
      performance, and suggest methods in which an individual surgeon can modify his or
      her specific learning curve in order to optimize surgical outcomes and patient
      safety. A defined personal learning contract may be a practical method for
      surgeons to proactively manage their individual learning curve and provide
      evidence of their efforts to safely improve surgical practice. 

PMID- 27049229
TI  - What Do Reported Learning Curves Mean for Orthopaedic Surgeons?
AB  - Practicing orthopaedic surgeons must assess the effects of the learning curve on
      patient safety and surgical outcomes if a new implant, technique, or approach is
      being considered; however, it remains unclear how learning curves reported in the
      literature should be interpreted and to what extent their results can be
      generalized. Learning curve reports from other surgical specialties and from
      orthopaedic surgery can be analyzed to identify the strengths and weaknesses of
      learning curve reporting. Single-surgeon series and registry data can be analyzed
      to understand learning challenges and to develop a personalized learning plan.
      Learning curve reports from single-surgeon series have several limitations that
      result from the limited dataset reported and inconsistencies in the way data are
      reported. Conversely, learning curve reports from registry data are likely to
      have greater generalizability, but are largely beneficial retrospectively, after
      data from a sufficient number of surgeons are assessed. There is a pressing need
      for surgeons to develop improved and consistent standards for learning curve
      reporting. Although registry data may provide better prospective measures in the
      future, the implementation of such registries faces several challenges. Despite
      substantial limitations, single-surgeon series remain the most effective way for
      practicing surgeons to assess their learning challenge and develop an appropriate
      learning plan. 

PMID- 27049230
TI  - Social Media and Orthopaedics: Opportunities and Challenges.
AB  - Social media presents unique opportunities and challenges for practicing
      orthopaedic surgeons. Social media, such as blogging, Facebook, and Twitter,
      provides orthopaedic surgeons with a new and innovative way to communicate with
      patients and colleagues. Social media may be a way for orthopaedic surgeons to
      enhance communication with patients and healthcare populations; however,
      orthopaedic surgeons must recognize the limitations of social media and the
      pitfalls of increased connectedness in patient care. 

PMID- 27049231
TI  - Influence of diabetes on natriuretic peptide thresholds in screening for Stage B
      heart failure.
AB  - CONTEXT: Natriuretic peptide (NP) has been shown to be an effective screening
      tool to identify patients with Stage B heart failure and to have clinical value
      in preventing heart failure progression. The impact of associated metabolic
      confounders on the screening utility of NP needs clarification. OBJECTIVE: To
      assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic
      Stage B heart failure. MATERIALS AND METHODS: The study population consisted of
      1368 asymptomatic patients with cardiovascular risk factors recruited from
      general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at
      point-of-care. RESULTS: BNP was found to be as accurate for detecting Stage B
      heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78]
      and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are
      required to achieve the same level of diagnostic sensitivity in DM compared with
      non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is
      required for patients with DM. CONCLUSION: Although a significantly different BNP
      threshold is detected for patients with DM, the BNP concentration difference is
      small and unlikely to warrant a clinically different diagnostic threshold.

PMID- 27049232
TI  - The improved dissolution performance of a post processing treated spray-dried
      crystalline solid dispersion of poorly soluble drugs.
AB  - CONTEXT: Solution-mediated transformation has been cited as one of the main
      problems that deteriorate dissolution performances of solid dispersion (SD). This
      is mainly attributed by the recrystallization tendency of poorly soluble drug.
      Eventually, it will lead to extensive agglomeration which is a key process in
      reducing the dissolution performance of SD and offsets the true benefit of SD
      system. Here, a post-processing treatment is suggested in order to reduce the
      recrystallization tendency and hence bring forth the dissolution advantage of SD
      system. OBJECTIVES: The current study investigates the effect of a post
      processing treatment on dissolution performance of SD in comparison to their
      performances upon production. METHODS: Two poorly soluble drugs were spray dried
      into SD using polyvinyl alcohol (PVA) as hydrophilic carrier. The obtained
      samples were post processing treated by exposure to high humidity, i.e. 75% RH at
      room temperature. The physical properties and release rate of the SD system were
      characterized upon production and after the post-processing treatment. RESULTS
      AND DISCUSSION: XRPD, Infrared and DSC results showed partial crystallinity of
      the fresh SD systems. Crystallinity of these products was further increased after
      the post-processing treatment at 75% RH. This may be attributed to the high
      moisture absorption of the SD system that promotes recrystallization process of
      the drug. However, dissolution efficiencies of the post-treated systems were
      higher and more consistent than the fresh SD. The unexpected dissolution trend
      was further supported by the results intrinsic dissolution and solubility
      studies. CONCLUSIONS: An increase of crystallinity in a post humidity treated SD
      did not exert detrimental effect to their dissolution profiles. A more stabilized
      system with a preferable enhanced dissolution rate was obtained by exposing the
      SD to a post processing humidity treatment.

PMID- 27049233
TI  - Opportunities for exploring and reducing prescription drug abuse through social
      media.

PMID- 27049234
TI  - Adapting and implementing an evidence-based asthma counseling intervention for
      resource-poor populations.
AB  - OBJECTIVE: To report implementation strategies and outcomes of an evidence-based
      asthma counseling intervention. The Head-off Environmental Asthma in Louisiana
      (HEAL) intervention integrated asthma counseling (AC) capacity and addressed
      challenges facing children with asthma in post-disaster New Orleans. METHODS: The
      HEAL intervention enrolled 182 children (4-12 years) with moderate-to-severe
      persistent asthma. Recruitment occurred from schools in the Greater New Orleans
      area for one year. Participants received home environmental assessments and
      tailored asthma counseling sessions during the study period based on the National
      Cooperative Inner City Asthma Study and the Inner City Asthma Study. Primary
      (i.e., asthma symptoms) and secondary outcomes (i.e., healthcare utilization)
      were captured. During the study, changes were made to meet the demands of a post
      hurricane and resource-poor environment which included changes to staffing,
      training, AC tools, and AC sessions. RESULTS: After study changes were made, the
      AC visit rate increased by 92.3%. Significant improvements were observed across
      several adherence measures (e.g., running out of medications (p = 0.009),
      financial/insurance problems for appointments (p = 0.006), worried about
      medication side-effects (p = 0.01), felt medications did not work (p < 0.001)).
      Additionally, an increasing number of AC visits was modestly associated with a
      greater reduction in symptoms (test-for-trend p = 0.059). CONCLUSION: By adapting
      to the needs of the study population and setting, investigators successfully
      implemented a counseling intervention that improved participant behaviors and
      clinical outcomes. The strategies for implementing the AC intervention may serve
      as a guide for managing asthma and other chronic conditions in resource-poor
      settings.

PMID- 27049235
TI  - Cognitive predictors of skilled performance with an advanced upper limb
      multifunction prosthesis: a preliminary analysis.
AB  - Purpose The objectives were to 1) identify major cognitive domains involved in
      learning to use the DEKA Arm; 2) specify cognitive domain-specific skills
      associated with basic versus advanced users; and 3) examine whether baseline
      memory and executive function predicted learning. Method Sample included 35
      persons with upper limb amputation. Subjects were administered a brief
      neuropsychological test battery prior to start of DEKA Arm training, as well as
      physical performance measures at the onset of, and following training. Multiple
      regression models controlling for age and including neuropsychological tests were
      developed to predict physical performance scores. Prosthetic performance scores
      were divided into quartiles and independent samples t-tests compared
      neuropsychological test scores of advanced scorers and basic scorers. Baseline
      neuropsychological test scores were used to predict change in scores on physical
      performance measures across time. Results Cognitive domains of attention and
      processing speed were statistically significantly related to proficiency of DEKA
      Arm use and predicted level of proficiency. Conclusions Results support use of
      neuropsychological tests to predict learning and use of a multifunctional
      prosthesis. Assessment of cognitive status at the outset of training may help set
      expectations for the duration and outcomes of treatment. Implications for
      Rehabilitation Cognitive domains of attention and processing speed were
      significantly related to level of proficiencyof an advanced multifunctional
      prosthesis (the DEKA Arm) after training. Results provide initial support for the
      use of neuropsychological tests to predict advanced learningand use of a
      multifunctional prosthesis in upper-limb amputees. Results suggest that
      assessment of patients' cognitive status at the outset of upper limb
      prosthetictraining may, in the future, help patients, their families and
      therapists set expectations for theduration and intensity of training and may
      help set reasonable proficiency goals.

PMID- 27049236
TI  - Increased Basement Membrane Components in Adipose Tissue During Obesity: Links
      With TGFbeta and Metabolic Phenotypes.
AB  - CONTEXT: Collagen accumulation around adipocytes and vessels (ie, pericellular
      fibrosis) is a hallmark of obese adipose tissue associated with altered
      metabolism. OBJECTIVE: Our objective was to evaluate components of basement
      membrane (BM) in adipose tissue, including collagen IV, a major BM component, and
      its relationships with metabolic parameters and TGFbeta isoforms. DESIGN AND
      SETTING: We used immuno-techniques and gene expression approaches to detect BM
      components in subcutaneous and visceral adipose tissue samples. Adipocytes and
      endothelial cells were isolated from lean and obese adipose tissue. We also
      focused on the expression of COL4A1 correlated to metabolic variables in moderate
      obesity and, in severe obesity before and after bariatric surgery. Using in vitro
      analysis, we explored the impact of TGFbeta isoforms on the expression of
      inflammatory and extracellular matrix genes in adipocytes and endothelial cells.
      RESULTS: BM components were detected around adipocytes and endothelial cells, and
      were increased in obese adipocytes. COL4A1 expression was positively correlated
      with insulin-resistance indices in obese subjects and showed less reduction in
      severely obese subjects with poorer insulin-resistance outcomes 6 months after
      gastric bypass. COL4A1 expression also correlated with TGFbeta1 and TGFbeta3 gene
      expressions in subcutaneous adipose tissue. Stimulating isolated adipocytes and
      endothelial cells in vitro with these TGFbeta isoforms showed an inflammatory and
      pro-fibrotic phenotype. However, TGFbeta1 and TGFbeta3 exposure only provoked
      COL4A1 overexpression in endothelial cells and not in adipocytes. CONCLUSION: The
      disorganization of several BM components, including collagen IV, could contribute
      to pathological alterations of obese adipose tissue and cells.

PMID- 27049237
TI  - Transverse spin relaxation and diffusion-constant measurements of spin-polarized
      129Xe nuclei in the presence of a magnetic field gradient.
AB  - The presence of a magnetic field gradient in a sample cell containing spin
      polarized (129)Xe atoms will cause an increased relaxation rate. We measured the
      transverse spin relaxation time of (129)Xe verse the applied magnetic field
      gradient and the cell temperature. We then compared the different transverse spin
      relaxation behavior of dual isotopes of xenon ((129)Xe and (131)Xe) due to
      magnetic field gradient in the same cell. The experiment results show the
      residual magnetic field gradient can be measured and compensated by applying a
      negative magnetic gradient in the sample cell. The transverse spin relaxation
      time of (129)Xe could be increased 2-7 times longer when applying an appropriate
      magnetic field gradient. The experiment results can also be used to determine the
      diffusion constant of (129)Xe in H2 and N2 to be 0.4 +/- 0.26 cm(2)/sec and 0.12
      +/- 0.02 cm(2)/sec. The results are close with theoretical calculation.

PMID- 27049238
TI  - Vitamin D level in rheumatoid arthritis and its correlation with the disease
      activity: a meta-analysis.
AB  - OBJECTIVES: This study aimed to evaluate the relationship between the 25
      hydroxyvitamin D [25(OH)D] level and rheumatoid arthritis (RA) and the
      correlation between serum vitamin D level and RA activity. METHODS: We searched
      the PUBMED, EMBASE, and Cochrane databases and performed a meta-analysis
      examining the vitamin D level and prevalence of vitamin D deficiency in patients
      with RA compared to healthy controls and the correlation coefficients between the
      vitamin D level and disease activity score 28 (DAS28) in RA patients. RESULTS:
      Fifteen studies that included a total of 1,143 RA patients and 963 controls were
      available for this meta-analysis. The meta-analysis showed that the serum vitamin
      D level in the RA group was significantly lower than that in the control group
      (SMD=-0.608, 95% CI=-1.105-[-0.017], p=0.017). In addition, the prevalence of
      vitamin D deficiency was significantly higher in the RA group than in the control
      group (55.2% vs. 33.2%; OR = 2.460, 95% CI = 1.135-5.332, p=0.023). Thirteen
      studies evaluated the correlation between the vitamin D level and its activity in
      924 RA patients. Meta-analysis showed a significant inverse correlation between
      the vitamin D level and DAS28 (Correlation coefficient =-0.278, 95% CI =-0.393-[
      0.153], p=1.8 x 10-5). CONCLUSIONS: Our meta-analysis demonstrates that serum
      vitamin D level is significantly low in patients with RA, vitamin D deficiency is
      prevalent in RA patients compared to controls, and the vitamin D level correlates
      inversely with RA activity. Our meta-analysis suggests that the vitamin D level
      is associated with susceptibility to RA and RA activity.

PMID- 27049239
TI  - Looking Beyond the Lumen.

PMID- 27049240
TI  - Intracranial Vessel Wall MRI: An Emerging Technique With a Multitude of Uses.
AB  - Intracranial vessel wall magnetic resonance imaging (VW-MRI) can be a useful
      diagnostic technique in patients with ischemic stroke and subarachnoid
      hemorrhage. Unlike conventional vascular imaging that depicts only the vessel
      lumen, VW-MRI allows visualization of pathology in the arterial wall itself. The
      ability to image the arterial wall is useful, as many pathological processes
      reside within the wall and only secondarily affect the lumen. In this review, we
      will present 6 clinical uses for intracranial wall imaging to highlight the
      versatility of this technique. 

PMID- 27049241
TI  - High-resolution Vessel Wall Magnetic Resonance Imaging in Intracranial Aneurysms
      and Brain Arteriovenous Malformations.
AB  - Over the last several years, the advent of intracranial high-resolution vessel
      wall magnetic resonance imaging (VW-MRI) has provided a new lens with which to
      view cerebrovascular disease that has not previously been available with
      conventional imaging. It has already fundamentally changed the way that steno
      occlusive diseases are evaluated at many academic centers. This review focuses on
      current and emerging applications of intracranial high-resolution VW-MRI in the
      clinical evaluation of intracranial aneurysms and brain arteriovenous
      malformations. Examples are provided from our clinical practice. 

PMID- 27049242
TI  - Molecular Imaging in Neurovascular Diseases: The Use of Ferumoxytol to Assess
      Cerebral Aneurysms and Arteriovenous Malformations.
AB  - Inflammation is increasingly being recognized as contributing to the underlying
      pathophysiology of cerebral aneurysms and brain arteriovenous malformation.
      Ferumoxytol is being increasingly used for both its prolonged intravascular
      imaging characteristics and its utility as an inflammatory marker when imaged in
      a delayed fashion. We aim to present a review article on the use of ferumoxytol
      to assess cerebral aneurysms and arteriovenous malformation. This could
      potentially help assist the physician in his judgment for intervening, as
      aneurysms that look macroscopically the same may behave differently. 

PMID- 27049243
TI  - Susceptibility-weighted Imaging in Neurovascular Disease.
AB  - Susceptibility-weighted imaging (SWI) has become an important imaging sequence in
      the evaluation of patients with neurovascular disease. In this review, we provide
      a general overview of the physics of SWI and describe how image contrast is
      produced with this technique. We provide a general approach and differential
      diagnosis for 2 commonly encountered radiographic patterns seen with SWI in
      neurovascular disease. Finally, we discuss specific neurovascular applications of
      SWI, including its application in acute stroke, vascular malformations, venous
      thrombosis, and evaluation of cerebral microbleeds. 

PMID- 27049244
TI  - Selective Arterial Spin Labeling: Techniques and Neurovascular Applications.
AB  - Knowledge of the distribution of blood flowing from the heart to the brain
      feeding arteries is important for the understanding and diagnosis of
      cerebrovascular diseases. Due to anatomical variations and anomalies within the
      cerebrovasculature, together with changes caused by various cerebrovascular
      diseases, there is high variability in the distribution of blood to the
      parenchyma. This article reviews the various methods that are available for
      determining the flow territories of the brain-feeding arteries and provides an
      overview of the different territorial arterial spin labeling (ASL) magnetic
      resonance imaging (MRI) techniques that have been introduced during the past 2
      decades. ASL is a noninvasive method that uses arterial blood as an endogenous
      contrast agent by magnetically labeling the inflowing blood with radiofrequency
      pulses. Several selective ASL MRI methods are available to visualize the
      perfusion territories of individual brain feeding arteries and determine the
      presence of collateral blood flow pathways. Clinically, these selective perfusion
      methods may replace more invasive procedures such as catheter angiography for
      various diseases in which it is of importance to determine the feeding blood
      vessels, evaluate the presence potential collateral pathways, and monitor the
      patency of surgical bypasses. 

PMID- 27049245
TI  - 4D Flow MRI in Neuroradiology: Techniques and Applications.
AB  - Assessment of the intracranial flow is important for the understanding and
      management of cerebral vascular diseases. From brain aneurysms and arteriovenous
      malformations lesions to intracranial and cervical stenosis, the appraisal of the
      blood flow can be crucial and influence positively on patients' management. The
      determination of the intracranial hemodynamics and the collateral pattern seems
      to play to a major role in the management of these lesions. 4D flow magnetic
      resonance imaging is a noninvasive phase contrast derived method that has been
      developed and applied in neurovascular diseases. It has a great potential if
      followed by further technical improvements and comprehensive and systematic
      clinical studies. 

PMID- 27049247
TI  - Peripheral blood used in place of bone marrow aspirate for detection of
      translocation t(11;14) status during minimal residual disease monitoring is cost
      effectiveness.

PMID- 27049246
TI  - 7-T MRI in Cerebrovascular Diseases: Challenges to Overcome and Initial Results.
AB  - Magnetic resonance imaging (MRI) plays a key role in the investigation of
      cerebrovascular diseases. Compared with computed tomography (CT) and digital
      subtraction angiography (DSA), its advantages in diagnosing cerebrovascular
      pathology include its superior tissue contrast, its ability to visualize blood
      vessels without the use of a contrast agent, and its use of magnetic fields and
      radiofrequency pulses instead of ionizing radiation. In recent years, ultrahigh
      field MRI at 7 tesla (7 T) has shown promise in the diagnosis of many
      cerebrovascular diseases. The increased signal-to-noise ratio (SNR; 2.3x and 4.7x
      increase compared with 3 and 1.5 T, respectively) and contrast-to-noise ratio
      (CNR) at this higher field strength can be exploited to obtain a higher spatial
      resolution and higher lesion conspicuousness, enabling assessment of smaller
      brain structures and lesions. Cerebrovascular diseases can be assessed at
      different tissue levels; for instance, changes of the arteries feeding the brain
      can be visualized to determine the cause of ischemic stroke, regional changes in
      brain perfusion can be mapped to predict outcome after revascularization, and
      tissue damage, including old and recent ischemic infarcts, can be evaluated as a
      marker of ischemic burden. For the purpose of this review, we will discriminate 3
      levels of assessment of cerebrovascular diseases using MRI: Pipes, Perfusion, and
      Parenchyma (3 Ps). The term Pipes refers to the brain-feeding arteries from the
      heart and aortic arch, upwards to the carotid arteries, vertebral arteries,
      circle of Willis, and smaller intracranial arterial branches. Perfusion is the
      amount of blood arriving at the brain tissue level, and includes the vascular
      reserve and perfusion territories. Parenchyma refers to the acute and chronic
      burden of brain tissue damage, which includes larger infarcts, smaller
      microinfarcts, and small vessel disease manifestations such as white matter
      lesions, lacunar infarcts, and microbleeds. In this review, we will describe the
      key developments in the last decade of 7-T MRI of cerebrovascular diseases,
      subdivided for these 3 levels of assessment. 

PMID- 27049248
TI  - Prostate cancer cell both microRNA aberrant expression-mediated autophagy and
      radiation therapy resistance with short cross-reference to epigenetic/genetic
      mechanism implications.

PMID- 27049249
TI  - The effect of a single intravitreal implantation of dexamethasone on the fellow
      eye in bilateral non-infectious uveitis - case report.
AB  - OBJECTIVE: To present the influence of dexamethasone intravitreal implant due to
      macular edema in non-infectious uveitis in the fellow eye. PATIENTS AND METHODS:
      A 25-year-old patient with a long history of juvenile arthritis with concomitant
      recurrent bilateral uveitis, complicated with increases of intraocular pressure
      and macular edema was treated with a single intravitreal dexamethasone implant
      into the eye with lower visual acuity. RESULTS: During a 36-month follow-up, the
      patient's bilateral visual acuity improved. The retinal thickness in both maculae
      decreased. CONCLUSIONS: Treating macular edema in the course of recurrent uveitis
      accompanying a systemic disease with dexamethasone depot in vitreous may play a
      beneficial role also in the fellow eye, when affected. This therapeutic effect in
      the fellow eye may suggest that the medication can penetrate into the circulatory
      system and reach such other organs as the fellow eye.

PMID- 27049250
TI  - Cow milk induced allergies (CMA) and asthma in new born.
AB  - The prevalence of asthma and allergic diseases in childhood has increased in
      several industrialized countries since the second half of the twentieth century.
      In some countries, the prevalence is still rising, although in others it seems to
      have plateaued or even decreased. It has been suggested that environmental
      factors operating prenatally and in early life affect the development of asthma
      and allergic diseases. Particularly changes in microbial exposure are proposed to
      play an important role in the development and maturation of the immune system.
      Thus, the factors that affect microbial exposure, such as mode of delivery and
      the use of antibiotics, may influence the development of asthma and allergic
      diseases. Several studies have explored the associations between perinatal
      factors and children's use of antibiotics and the risk of asthma, with
      inconsistent findings. The present review article will be focused on the
      important findings related with factors responsible for above allergic reactions
      along with asthma in young infants. Also, the influence of cow milk intake will
      also be taken in account to cover the aspect of cow milk induced allergies and
      asthma in infants. 

PMID- 27049251
TI  - The association of vascular endothelial growth factor, metalloproteinases and
      their tissue inhibitors with cardiovascular risk factors in the metabolic
      syndrome.
AB  - OBJECTIVE: The present study was proposed to examine the matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and
      vascular endothelial growth factor (VEGF) in patients with metabolic syndrome
      (MetS), and to compare these parameters with healthy controls. We also compared
      the possible association of the circulating levels of MMP-2, MMP-9, TIMP-1, TIMP
      2, and VEGF with cardiovascular risk factors in patients with MetS. We also
      compared the possible association of the circulating levels of MMP-2, MMP-9, TIMP
      1, TIMP-2, and VEGF with cardiovascular risk factors in patients with MetS.
      PATIENTS AND METHODS: A total of 45 patients with MetS and 17 healthy controls
      with a body mass index (BMI) less than 25 kg/m2 were enrolled in the study.
      Plasma MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF levels were determined using ELISA.
      RESULTS: TIMP-1,-2, MMP-2,-9 levels were significantly higher in patients with
      MetS compared with healthy controls (p < 0.001). Carotid intima-media thickness
      and serum VEGF levels were found to be significantly increased (p < 0.01, p <
      0.05 respectively) in MetS compared with healthy controls. According to the ROC
      curves, TIMP-1 levels were both sensitive (93.3%) and specific (81.2%).
      CONCLUSIONS: We observed that the patients with MetS have increased circulating
      concentrations of MMP-9, MMP-2, and TIMP-1, TIMP-2 that are associated with
      increased concentrations of VEGF. These findings suggest that MMP-2 may have a
      role in the increased cardiovascular risk of MetS patients.

PMID- 27049252
TI  - Nesfatin-1 hormone levels in morbidly obese patients after laparoscopic sleeve
      gastrectomy.
AB  - OBJECTIVE: To investigate changes in body mass index (BMI) and nesfatin-1 levels
      in patients with morbid obesity who had undergone laparoscopic sleeve gastrectomy
      (LSG). PATIENTS AND METHODS: Blood samples were collected from, and the BMI
      calculated of 30 morbidly obese patients pre-surgery and at 3 and 6 months post
      surgery. Nesfatin-1 hormone levels were measured using enzyme-linked
      immunosorbent assay (ELISA). Descriptive statistical analysis of the data was
      performed using Kruskal-Wallis variance analysis, one-way ANOVA, and the
      Bonferroni-Dunn test. The correlations between continuous variables not
      displaying normal distribution and those displaying normal distributions were
      analyzed using the Spearman correlation test and the Pearson correlation test,
      respectively. RESULTS: The mean age of the 30 patients was 41.23 +/- 10.37 years.
      The mean BMI values (kg/m2) were 49.30 +/- 7.92, 39,48 +/- 7.32, and 34.39 +/-
      7.56 presurgery, three months post-surgery, and six months post-surgery,
      respectively (p < 0.001). Mean nesfatin-1 levels (ng/ml) were 22.80 +/- 14.16,
      60.23 +/- 52.92, and 96.99 +/- 40.20 presurgery, three months post-surgery, and
      six months post-surgery, respectively (p < 0.001). The postoperative months 3 and
      6 BMI values were significantly lower than the preoperative BMI value and the
      postoperative month 6 BMI value was significantly lower than the postoperative
      month 3 BMI value (p < 0.001). The postoperative months 3 and 6 nesfatin-1 levels
      were significantly higher than the preoperative nesfatin-1 levels. A negative
      correlation was found between age and preoperative nesfatin-1 values (p = 0.001,
      r = -0.0557). CONCLUSIONS: Observation of significant increases in nesfatin-1
      hormone levels in morbidly obese patients who had undergone LSG indicate that
      nesfatin-1 has important anorexigenic effects post-surgery and may be an
      important component of future obesity treatments.

PMID- 27049253
TI  - Characteristic analysis of white matter lesions in migraine patients with MRI.
AB  - OBJECTIVE: The aim of this study is to analyze the characteristics of white
      matter lesions in abnormal manifestations of magnetic resonance imaging (MRI) of
      patients with migraine, and its relationship with migraine. PATIENTS AND METHODS:
      38 patients, diagnosed with migraine were continuously selected as the
      observation group, while during the same period, 30 healthy individuals were
      selected as the control group. The differences of the features of MRI of two
      groups, the ratios of white matter lesions manifestations and the severity were
      compared. RESULTS: The manifestations of MRI in patients with migraine were
      mainly white matter lesions. The accuracy rate was 86.7%, and the sensibility was
      92.3%. According to Wahlund white matter lesions classifications, patients with
      migraine were mainly Level II and Level III (84.2%). It can be acquired from
      relevant analyses that white matter lesions classifications and the degrees of
      migraine were positively correlated (p < 0.05). White matter lesions were mainly
      distributed in the frontal lobe (78.9%), limbic system (60.5%) and parietal lobe
      (28.9%). CONCLUSIONS: The MRI of migraine, the manifestations of white matter
      lesions were relatively sensitive. The higher the classification was linked with
      the degree of migraine. They were mainly distributed in the frontal lobe, limbic
      system and parietal lobe.

PMID- 27049254
TI  - Quantitative fibrosis parameters highly predict esophageal-gastro varices in
      primary biliary cirrhosis.
AB  - OBJECTIVE: Esophageal-gastro Varices (EGV) may develop in any histological stages
      of primary biliary cirrhosis (PBC). We aim to establish and validate quantitative
      fibrosis (qFibrosis) parameters in portal, septal and fibrillar areas as ideal
      predictors of EGV in PBC patients. PATIENTS AND METHODS: PBC patients with liver
      biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon
      Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in
      this study. qFibrosis parameters in portal, septal and fibrillar areas were
      acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was
      identified using multivariate logistic regression analysis. PATIENTS AND METHODS:
      PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic
      Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were
      retrospectively enrolled in this study. qFibrosis parameters in portal, septal
      and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system.
      Independent predictor was identified using multivariate logistic regression
      analysis. RESULTS: Among the forty-nine PBC patients with qFibrosis images,
      twenty-nine PBC patients with both esophagogastroscopy data and qFibrosis data
      were selected out for EGV prognosis analysis and 44.8% (13/29) of them had EGV.
      The qFibrosis parameters of collagen percentage and number of crosslink in
      fibrillar area, short/long/thin strings number and length/width of the strings in
      septa area were associated with EGV (p < 0.05). Multivariate logistic analysis
      showed that the collagen percentage in fibrillar area >= 3.6% was an independent
      factor to predict EGV (odds ratio 6.9; 95% confidence interval 1.6-27.4). The
      area under receiver operating characteristic (ROC), diagnostic sensitivity and
      specificity was 0.9, 100% and 75% respectively. CONCLUSIONS: Collagen percentage
      in CONCLUSIONS: Collagen percentage in the fibrillar area as an independent
      predictor can highly predict EGV in PBC patients.

PMID- 27049255
TI  - Prioritization of high-cost new drugs for HCV: making sustainability ethical.
AB  - Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic
      HCV infection may in the long run cause cirrhosis, hepatic decompensation and
      hepatocellular carcinoma, with an ultimate disease burden of at least 350,000
      deaths per year worldwide. The new generation of highly effective direct acting
      antivirals (DAA) to treat HCV infection brings major promises to infected
      patients in terms of exceedingly high rates of sustained virological response
      (SVR) but also of tolerability, allowing even the sickest patients to be treated.
      Even in the face of the excellent safety and efficacy and wide theoretical
      applicability of these regimens, their introduction is currently facing cost and
      access issues denying their use to many patients in need. Health systems in all
      countries are facing a huge problem of distributive justice, since while they
      should guarantee individual rights, among which the right to health in its
      broader sense, therefore not limited to healing, but extended to quality of life,
      they must also grant equal access to the healthcare resources and keep the
      distribution system sustainable. In the face of a disease with a relatively
      unpredictable course, where many but not of all chronically infected will
      eventually die of liver disease, selective allocation of this costly resource is
      debatable. In most countries the favorite solution has been a stratification of
      patients for prioritization of treatment, which means allowing Interferon-free
      DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping
      on hold persons with lesser stages of liver disease. In this report, we will
      perform an ethical assessment addressing the issues linked to access to new
      therapies, prioritization and eligibility criteria, analyzing the meaning of the
      term "distributive justice" and the different approaches that can guide us
      (individualistic libertarianism, social utilitarianism and egalitarianism) on
      this specific matter. Even if over time the price of new DAA will be reduced
      through competition and eventual patent expiration, the phenomenon of high drug
      costs will go on in the next decades and we need adequate tools to face the
      problems of distributive justice that come with it. 

PMID- 27049256
TI  - Epidemiological characteristics and risk factors of hepatitis C virus genotype 1
      infection: a national epidemiological survey of Chinese Han population.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection is a high morbidity disease in
      China. The aim of this study was to explore the latest distribution of HCV
      genotypes in China, mainly focusing on epidemiological characteristics and risk
      factors of HCV genotype 1 in Chinese Han population. PATIENTS AND METHODS: 793
      HCV-positive patients were enrolled from 21 hospitals across China. The
      association of epidemiological data with HCV genotype 1 and the potential risk
      factors was analyzed using univariate and multivariate logistic regression
      analysis. RESULTS: The HCV genotype 1b was detected in 66.9% of 793 patients. The
      way of infection, disease course, HCV RNA level, history of blood transfusion and
      smoking were found to be significantly different between patients infected with
      HCV genotype 1 and non-genotype 1. The result of univariate logistic regression
      analysis showed that HCV genotype 1 infection has a close relationship with age,
      gender, smoking history, the way of infection, allergy, disease course, and HCV
      RNA level. Moreover, the HCV RNA level, disease course, and blood transfusion
      history were the related risk factors for infection of HCV genotype 1 as
      demonstrated by multivariate logistic regression analysis. CONCLUSIONS: The HCV
      genotype 1 was still the main genotype of HCV infection in China. We should
      intensify HCV screening for those people who aged over 50 years and had a history
      of blood transfusion in China. The treatment of genotype 1 should be paid more
      attention in antiviral of HCV.

PMID- 27049257
TI  - PRAME promotes in vitro leukemia cells death by regulating S100A4/p53 signaling.
AB  - OBJECTIVE: PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor
      associated antigen recognized by immunocytes, and it induces cytotoxic T cell
      mediated responses in melanoma. PRAME is expressed in a wide variety of tumors,
      but in contrast with most other tumor-associated antigens, it is also expressed
      in leukemias. The physiologic role of PRAME remains elusive. Recently, it has
      found PRAME could be involved in the regulation of cell death in leukemias, but
      the mechanism of the function is unclear. Here, we confirm that PRAME induces
      leukemias cell death by regulation of S100A4/p53 signaling. MATERIALS AND
      METHODS: The pCDNA3-PRAME plasmid and its control were transfected with the KG-1
      cells. The pCDNA3-PRAME transfected KG-1 cells were then transiently transfected
      with S100A4 cDNA or wt-p53 siRNA. The PRAME siRNA and its control were
      transfected with the K562 cells. The PRAME siRNA transfected K562 cells were then
      transiently transfected with S100A4 siRNA or pGMp53-Lu. PRAME, S100A4 and P53
      were detected by Western blot assay in different time point. Annexin V/propidium
      iodide and MTT methods were used to detect apoptosis and cell survival rate.
      RESULTS: KG-1 cells overexpressing the PRAME gene significantly induces apoptosis
      and decreases proliferation in vitro, followed by down-regulation of S100A4 and
      up-regulation of p53. Up-regulation of S100A4 by S100A4 transfection inhibits
      PRAME-induced p53 up-regulation. Furthermore, up-regulation of S100A4 by S100A4
      transfection or down-regulation of p53 by p53 siRNA transfection reduces
      apoptosis and increases proliferation in vitro. Knockdown of PRAME in K562 cells
      significantly increases proliferation in vitro, followed by up-regulation of
      S100A4 and down-regulation of p53. The downregulation of S100A4 by S100A4 siRNA
      transfection increased p53 expression. Furthermore, downregulation of S100A4 by
      S100A4 siRNA transfection or up-regulation of p53 by p53 transfection decreases
      proliferation in vitro. CONCLUSIONS: Our results suggest that the leukemias
      expressing high levels of PRAME has a favorable prognosis. PRAME promotes in
      vitro leukemia cells death by regulating S100A4/p53 signaling.

PMID- 27049258
TI  - Advance in the study on p38 MAPK mediated drug resistance in leukemia.
AB  - Leukemia is a group of malignant clone diseases of hematopoietic stem cells,
      while drug resistance (DR) has become the primary cause of chemotherapy failure.
      p38 mitogen-activated protein kinase (p38MAPK) signaling pathway induces cell
      activation, proliferation and apoptosis in response to extracellular stimuli.
      Recent studies have shown that p38 MAPK signaling pathway is closely associated
      with DR in leukemia. The present article reviews the relationship between p38
      MAPK signaling pathway and DR in leukemia. 

PMID- 27049259
TI  - Silencing of NUF2 inhibits proliferation of human osteosarcoma Saos-2 cells.
AB  - OBJECTIVE: NUF2 (NUF2, Ndc80 kinetochore complex component), which is essential
      for kinetochore-microtubule attachment in mitosis, has emerged as a critical
      mediator of the cell cycle in multiple tumour occurrences. In the present study,
      we aimed to investigate the role of NUF2 in osteosarcoma, one of the most common
      primary bone tumours in children and young adults. MATERIALS AND METHODS:
      Lentivirus-mediated short-hairpin RNA (shRNA) targeting NUF2 (Lv-shNUF2) was
      employed for evaluation in human osteosarcoma Saos-2 cells. After NUF2 silencing,
      the proliferation of Saos-2 cells was significantly inhibited, as determined by
      the MTT assay. RESULTS: The colony forming ability was also significantly
      decreased in Saos-2 cells infected with Lv-shNUF2. Flow cytometry revealed that
      downregulation of NUF2 in Saos-2 cells caused a remarkable accumulation of the
      cell population in the S phase. Furthermore, the expression levels of cell cycle
      regulators cyclin A and cyclin-dependent kinase 2 (CDK2) were notably decreased,
      whereas those of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, were
      increased in response to NUF2 knockdown in Saos-2 cells. CONCLUSIONS: Our
      findings suggest that NUF2 might modulate cell proliferation via cell cycle
      control in Saos-2 cells. Downregulation of NUF2 by shRNA might be a novel
      strategy for early treatment of osteosarcoma using molecular-targeting therapy.

PMID- 27049260
TI  - MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via
      epithelial mesenchymal transition.
AB  - OBJECTIVE: Down-regulation of miR-138 is observed in a variety of cancers, which
      suggests that miR-138 may be involved in cancer pathogenesis. Our current work
      aimed to evaluate the effects of miR-138 in adriamycin (ADM)-resistant human
      NSCLC cells. MATERIALS AND METHODS: Cell proliferation was determined by MTT
      assay. Real-time PCR and western blot were performed to detect the mRNA and
      protein expression levels. The target of miR-138 was validated by luciferase
      activity assay. RESULTS: Compared with the chemosensitive parental cells, miR-138
      was remarkably decreased in A549/ADM and NCI-H23/ADM cells. Ectopic expression of
      miR-138 sensitized chemoresistant tumor cells to ADM administration. In addition,
      the epithelial-mesenchymal transition (EMT) related markers E-cadherin or
      vimentin was up-regulated or down-regulated upon the overexpression of miR-138 in
      NSCLC cells. Further studies identified zinc finger E-box-binding homeobox 2
      (ZEB2) as the target of miR-138 and up-regulation of miR-138 suppressed the mRNA
      and protein expression of ZEB2. Notably, luciferase reporter assay confirmed that
      ZEB2 was a direct target of miR-138. CONCLUSIONS: Our study demonstrates that miR
      138 sensitizes NSCLC cells to ADM via EMT, suggesting that miR-138 might be a
      potential therapeutic target for drug-resistant NSCLC patients.

PMID- 27049261
TI  - DTC chemotherapy regimen is associated with higher incidence of premature ovarian
      failure in women of reproductive age with breast cancer.
AB  - OBJECTIVE: Different chemotherapy regimens may contribute differently to the
      development of Premature Ovarian Failure (POF) in women of reproductive age with
      breast cancer. Here we evaluated how two different chemotherapy regimens, CAF
      (tegafur + pirarubicin + ifosfamide) and DTC (docetaxel + pirarubicin +
      ifosfamide), affect the development of POF. PATIENTS AND METHODS: We enrolled 164
      women of reproductive age with breast cancer (mean +/- SD age of 34.56 +/- 9.48
      years). The patients were divided into two groups, which were respectively
      treated with CAF (n = 89) or DTC (n = 75) chemotherapy regimen. Both study groups
      were comparable in all analyzed characteristics at baseline. Patients were
      treated with respective chemotherapy regimen for 6 months and followed up for
      over 12 months after completion of chemotherapy. Study outcomes were occurrence
      rates of POF, menstrual status and recovery after completion of chemotherapy, and
      serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and
      oestradiol (E2). RESULTS: At 6 months after completion of chemotherapy, POF
      incidence rates were significantly lower in the CAF group. Furthermore, the
      proportion of patients with eumenorrhea, menstrual disorders or chemotherapy
      induced amenorrhea in this study group was also significantly different from the
      DTC group. Similarly, adverse changes of serum levels of FSH, LH and E2 were less
      pronounced in the CAF group. CONCLUSIONS: Both tested chemotherapy regimens can
      cause POF; however, adverse effects of DCT chemotherapy regimen on ovarian
      function are more pronounced than those by CAF chemotherapy regimen.

PMID- 27049262
TI  - Mechanism of action of EBV, Bcl-2, p53, c-Myc and Rb in non-Hodgkin's lymphoma.
AB  - OBJECTIVE: The aim of the present study is to explore the mechanism of action of
      several proteins, including Epstein-Barr virus (EBV), B-cell lymphoma (Bcl)-2,
      p53, c-Myc and retinoblastoma (Rb), in Non-Hodgkin's lymphoma (NHL). PATIENTS AND
      METHODS: Between July 2010 and July 2015, samples of 142 patients with
      pathologically confirmed NHL which presented at our institution were included in
      the observation group. In addition, samples from 55 patients with hyperplastic
      lymphadenitis presented during the same period were enrolled as control group.
      The expressions of EBV (+), p53(+), Bcl-2(+), Rb(-) and c-Myc(+) were determined
      and compared PATIENTS AND METHODS: Between July 2010 and July 2015, samples of
      142 patients with pathologically confirmed NHL which presented at our institution
      were included in the observation group. In addition, samples from 55 patients
      with hyperplastic lymphadenitis presented during the same period were enrolled as
      control group. The expressions of EBV (+), p53(+), Bcl-2(+), Rb(-) and c-Myc(+)
      were determined and compared among different subtypes and stages of NHLs of
      observation group. Besides, the correlation of EBV with p53, Bcl-2, Rb and c-Myc
      were investigated in NHLs of observation group. RESULTS: In the observation
      group, the expression rates of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) were
      significantly higher than those, respectively, in the control group (p < 0.05).
      No significant correlation was observed between EBV expression and the
      expressions of p53, Bcl-2, Rb and c-Myc in the observation group (p > 0.05). The
      expression rates of p53(+) and Bcl-2(+) were significantly higher in aggressive
      and highly-aggressive NHLs than in indolent NHLs of the observation group (p <
      0.05). The expressions of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) were
      significantly higher in stage III-IV NHLs than in stage I-II NHLs (p < 0.05).
      CONCLUSIONS: The expressions of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) are
      closely associated with NHL pathogenesis. Expressions of these proteins are
      higher in later stages of NHLs, and expressions of p53(+) and Bcl-2(+) are higher
      in more aggressive NHLs.

PMID- 27049263
TI  - Inhibition of the JNK signaling pathway increases sensitivity of hepatocellular
      carcinoma cells to cisplatin by down-regulating expression of P-glycoprotein.
AB  - OBJECTIVE: The resistance of hepatocellular carcinoma (HCC) to chemotherapy may
      be mediated by the c-Jun N-terminal kinase (JNK) pathway. We wished to verify the
      involvement of this pathway in resistance of HCC cells to cisplatin. MATERIALS
      AND METHODS: We used HepG2 cell line and cisplatin-resistant clone (HepG2/DDP).
      Expressions of drug resistance and apoptosis-related genes were analyzed by qPCR.
      Protein expressions were assessed by Western blot. The JNK pathway was assessed
      as total JNK1/2 and JNK1/2 phosphorylation. Cell growth kinetics was quantified
      by the CCK-8 assay, and cell apoptosis (Annexin V / propidium iodide) by flow
      cytometry. RESULTS: HepG2/DDP cells were more resistant and less apoptotic on
      cisplatin. Expression of drug-resistance genes MDR1, MRP1 and MPR2 was
      significantly up-regulated in HepG2/DDP cells (p < 0.05), with up-regulation of
      MDR1 being the highest. This was confirmed by Western blot analysis of P
      glycoprotein (P-gp), MRP1 and MRP2 proteins, the proteins encoded by the above
      genes. Expression of anti-apoptotic genes Bcl-2 and Bcl-XL was significantly up
      regulated, and expression of pro-apoptotic genes Bak and Bad was significantly
      reduced, in HepG2/DDP cells (p < 0.05). Cisplatin treatment of HepG2 led to
      increased phosphorylation of JNK1/2; the trend reversed by the inhibitor
      SP600125. Furthermore, cisplatin increased expression of P-gp, which was also
      attenuated by SP600125. Cell growth was inhibited more substantially, and cell
      apoptosis promoted, when HepG2 cells were exposed to both cisplatin and SP600125.
      CONCLUSIONS: Inhibition of the JNK signaling pathway enhances the sensitivity of
      HCC cells to cisplatin by down-regulating the expression of P-gp.

PMID- 27049264
TI  - MicroRNA-138 inhibits proliferation of cervical cancer cells by targeting c-Met.
AB  - OBJECTIVE: MicroRNAs (miRNAs) function as important post-transcriptional
      regulators involved in a wide range of biological behaviors. MicroRNA-138 (miR
      138) has been shown to play a critical role in tumor pathogenesis, the present
      study aimed to investigate the role of miR-138 in cervical cancer. MATERIALS AND
      METHODS: CCK-8 assay was performed to measure the viabilities of cancer cells.
      Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the
      mRNA and protein expression, respectively. Moreover, the miRNA target genes were
      validated with luciferase activity assay. RESULTS: In the current study, we found
      that the expression of miR-138 was significantly down-regulated in cervical
      cancer tissues compared to the adjacent non-cancer tissues. CCK-8 assay showed
      that over-expression of miR-138 suppressed the proliferation of four cervical
      cancer cell lines including HeLa, SiHa, C33A and CaSki. By contrast, down
      regulation of miR-138 promoted the growth of cervical cancer cells. In addition,
      increased expression of miR-138 led to a reduction in c-Met expression, whereas
      inhibition of miR-138 enhanced c-Met levels in cervical cancer cells. The
      luciferase reporter assay showed that c-Met was a direct target of miR-138 in
      cervical cancer cells. CONCLUSIONS: These findings demonstrated that miR-138
      inhibited cervical cancer cells proliferation via c-Met, providing a novel target
      for the molecular treatment of cervical cancer.

PMID- 27049265
TI  - USP4 promotes invasion of breast cancer cells via Relaxin/TGF-beta1/Smad2/MMP-9
      signal.
AB  - OBJECTIVE: Ubiquitin-specific protease 4 (USP4) is a deubiquitinating enzyme with
      key roles in the regulation of TGF-beta1 signaling, suggesting its importance in
      tumorigenesis. However, the underlying mechanisms causing this are not entirely
      clear. In the present study, we investigated the effect of USP4 on invasion and
      tumorigenesis of breast cancer cells, and explored its mechanism. MATERIALS AND
      METHODS: Effects of USP4 overexpression or USP4 silencing by small interfering
      RNA (USP4 siRNA) on invasion of breast cancer MDA-MB-231 and T47D cells in vitro
      was detected. Using siRNAs and inhibitors to examine the USP4 signaling pathway.
      RESULTS: The migration and invasion assays showed that USP4 promotes human breast
      cancer cell migration and invasion by USP4 overexpression, and knockdown of USP4
      by siRNA inhibits human breast cancer cell migration and invasion. Treatment with
      RLX siRNAs, TGF-beta1 siRNAs, Smad2 siRNAs or BB94 (MMPs inhibitor) to USP4
      overexpressing breast cancer cells revealed that USP4- induced RLX via TGF-beta1
      pathway promotes the cell migration and invasion. Further studies demonstrated
      that USP4-mediated TGF-beta1 activation not only enhances the phosphorylation of
      Smad2 through TGF-beta, but also directly upregulate matrix metalloproteinase
      (MMP)-9-mediated cell migration and invasion of breast cancer cells. CONCLUSIONS:
      Therapies targeting the USP4 inhibits invasion of breast cancer cells via
      Relaxin/TGF-beta1/Smad2/MMP-9 signal. These results indicate that USP4 is an
      attractive target for breast cancer therapy.

PMID- 27049266
TI  - Assessment of cardiac arrhythmias in patients with ankylosing spondylitis by
      signal-averaged P wave duration and P wave dispersion.
AB  - OBJECTIVE: Aortic regurgitation, conduction disturbances, increased myocardial
      fibrosis and pericarditis could be seen in ankylosing spondylitis (AS). However,
      less attention has been paid to supraventricular arrhythmias (SVA) and atrial
      conduction system changes. We aimed to assess SVA and conduction system changes
      in patients with AS. PATIENTS AND METHODS: Twenty-eight patients (24 men; mean
      age, 28.7 +/- 5.7 years) with AS and 30 healthy volunteers (26 men; mean age,
      29.3 +/- 5.8 years) were enrolled. All subjects were evaluated by 24-hour
      ambulatory electrocardiogram, 12 lead standard electrocardiogram (ECG) for P wave
      dispersion (Pd), and signal-averaged ECG (SAECG) for P wave duration (SAPWD).
      RESULTS: SVAs were detected in 9 patients with AS (32%) and 3 controls (10%; p
      =0.02). Mean SAPWD (115.7+/-28.6 ms vs. 100.2 +/- 18.7 ms, p =0.017) and mean Pd
      (11.9+/-4.8 ms vs. 9.3+/-3.6 ms, 0.023) was longer in patients with AS than the
      control group. When patient with AS were divided into 2 subgroups as patients
      with or without SVA, the Pd (16.2+/-5.0 vs. 9.9+/-3.2, p =0.001), SAPWD (151.4+/
      7.8 vs. 98.7+/-16.1, p =0.001) and Bath ankylosing spondylitis disease activity
      index (BASDAI) (5.1+/-1.6 vs. 3.7+/-1.0, p =0.014) were significantly greater in
      the subgroup with arrhythmias compared to the subgroup without arrhythmias. There
      was a moderate positive correlation between BASDAI and SAPWD (r=0.622, p =0.001).
      There was also a moderate positive correlation between BASDAI and Pd (r=0.479, p
      =0.01). CONCLUSIONS: SVA were detected more frequently in AS than control group.
      SAPWD and Pd were prolonged in patients with AS. Clinical severity assessed with
      BASDAI had a positive correlation with prolongation of SAPWD and Pd.

PMID- 27049267
TI  - Clinical observation on pericardiocentesis and glucocorticoid in the treatment of
      tuberculous pericarditis.
AB  - OBJECTIVE: To investigate peri-cardiocentesis and glucocorticoids in the treat
      ment of the clinical curative effect of tubercu-lous pericarditis. PATIENTS AND
      METHODS: Choose 128 cases of our hospital diagnosed as tuberculous peri-carditis
      patients as the research object, accord-ing to the treatment, were divided into
      group A (pericardium puncture + anti-tuberculosis (an-ti-TB) treatment of 26
      cases) and group B (peri-cardium puncture +anti-tuberculosis (anti-TB) +
      glucocorticoid treatment of 30 cases), group C (anti-tuberculosis (anti-TB) +
      glucocorticoid therapy of 24 cases, and group D anti-tuberculo-sis (anti-TB)
      treatment of 48 cases, in the treat-ment of 8 weeks, 3 months, 6 months, 9
      months, 12 months, 18 months by B ultrasonic and CT ex-amination to observe the
      efficacy of treatment. RESULTS: At 8 weeks after treatment in group A, group B
      and group C and group D efficient were 61.54%, 93.33%, 54.17%, and 68.75%,
      respective-ly, group B, respectively, compared with group A, group C, and group
      D, had obvious statistical sig-nificance difference (p < 0.05); Groups of early
      and late treatment comparison difference have no sta-tistical significance (p >
      0.05). CONCLUSIONS: Tuberculous pericarditis in anti-TB treatment on the basis of
      using pericar-diocentesis and sugar cortical hormone treat-ment, can achieve an
      ideal effect.

PMID- 27049268
TI  - Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial
      lesions.
AB  - OBJECTIVE: The present study aims to investigate the correlation between serum
      level of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the severity
      of coronary arterial lesion in patients with coronary heart disease (CHD).
      PATIENTS AND METHODS: Between August 2010 and January 2015, 126 CHD patients and
      70 patients with coronary arterial stenosis < 50% (controls) were included in the
      present study. Serum PCSK9 level was determined using ELISA. Demographic
      characteristics, relevant clinical data and biochemical data were collected from
      all patients, and their relationship with PCSK9 was analyzed to evaluate the
      correlation of PCSK9 expression with the severity of coronary artery disease
      (CAD). RESULTS: Concentrations of total cholesterol (TC) and fasting blood sugar
      (FBS) were significantly higher in CHD patients than in controls (p < 0.05). No
      significant differences were observed in gender, age, body mass index (BMI),
      triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), family history, smoking history and history of
      hypertension between groups (p > 0.05). Serum PCSK9 levels in the CHD group were
      significantly higher than those in the control group [(96.4 +/- 33.2) ng/mL vs.
      (81.8 +/- 27.6) ng/mL, p < 0.05]. Compared with those of patients with single
      vessel or double-vessel disease, PCSK9 levels were significantly elevated in
      patients with multi-vessel disease (p < 0.05). The Gensini score of the CHD group
      was significantly lower than that of the control group (11.4 +/- 10.5 vs. 37.3 +/
      10.3, p < 0.05). The Gensini score of patients with multi-vessel disease was
      significantly higher compared with patients of single-vessel  or double-vessel
      disease (p < 0.05). Correlation analysis revealed that PCSK9 was positively
      correlated with many clinical parameters, including age, BMI, TC, TG, systolic
      blood pressure, FBS, Gensini score and LDL-C (p < 0.05). However, PCSK9 was not
      correlated with either gender ratio or diastolic blood pressure (p > 0.05).
      CONCLUSIONS: Serum PCSK9 level is significantly elevated in CHD patients and its
      variation is correlated with the severity of CAD.

PMID- 27049269
TI  - Sedoanalgesia for cardioversion: comparison of alfentanil, remifentanil and
      fentanyl combined with propofol and midazolam: a prospective, randomized, double
      blind study.
AB  - OBJECTIVE: Electrical cardioversion (EC) is a short but painful procedure to
      restore sinus rhythm. The aim of this study is to compare the effect of fentanyl,
      remifentanil and alfentanil in association with propofol and midazolam for
      elective EC. PATIENTS AND METHODS: Ninety-nine patients older than 18-years,
      American Society of Anesthesiologists I/II/III grades undergoing elective EC were
      randomized into 3 groups. All patients received 2 mg midazolam and propofol (0.5
      mg/kg). Group A received alfentanil (5 ug/kg i.v. bolus), Group F received
      fentanyl (0.5 ug/kg i.v. bolus) and Group R received remifentanil (0.25 ug/kg
      i.v. bolus). Hemodynamics and respiratory variables [Heart rate (HR), systolic
      blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure
      (MAP), SpO2, respiratory rate (RR)], and Modified Aldrete recovery score (MARS)
      were assessed at six different time points (baseline, right after EC, and 3rd
      min, 5th min, 10th min, 30th min following EC). Also, induction times (time to
      reach RSS to 5) and recovery times (time to reach MARS to 8) were recorded. The
      incidence of respiratory depression, bradycardia, hypotension and adverse effects
      were also recorded. RESULTS: Hemodynamic variables were similar in all groups.
      SpO2 values in Group R were significantly lower at 3rd min (p = 0.005). Induction
      and recovery times were longest in Group F. There were significant differences at
      3rd, 5th and 10th minute MARS values between groups. The incidence of hypotension
      and bradycardia were similar in all groups (p > 0.05) but respiratory depression
      was higher in Group R (p = 0.047). CONCLUSIONS: Propofol alfentanil combination
      has more beneficial advantages in their rapid onset, early recovery time and less
      respiratory depression than remifentanil and fentanyl.

PMID- 27049270
TI  - BNP shows myocardial injury earlier than Troponin-I in experimental carbon
      monoxide poisoning.
AB  - OBJECTIVE: In this study, our purpose was to determine whether plasma BNP level
      can be useful or not in determining the severity of myocardial injury formed by
      CO poisoning and to compare plasma BNP level with serum cTnI level. MATERIALS AND
      METHODS: In the study, 46 female Wistar Albino rats were used. Rats were divided
      into four groups, one control group and three poisoning groups. The mixture of
      pure CO and air was injected for 60 minutes to provide 3000 ppm CO concentration.
      Blood samples of groups were collected to measure COHb, BNP and cTnI levels.
      Blood samples of poisoning groups were collected at the 1st, 6th and 12th hours
      after poisoning. After biochemical procedures, findings were analysed
      statistically and compared with each other. RESULTS: Eight rats which died in
      poisoning groups were excluded and 38 rats were evaluated. BNP levels were high
      in all poisoning groups compared to control group and the difference between them
      was statistically significant (p < 0.05). cTnI levels were high in 6th and 12th
      hours poisoning groups compared to control and 1st hour group but only 12th hour
      group had statistically significant difference (p < 0.05). A statistically
      positive relation was established between BNP and cTnI levels in 6th and 12th
      hour groups (R: 0.76 - p < 0.05 - n:38). CONCLUSIONS: It was found that BNP
      levels increased earlier than cTnI levels in acute severe CO poisoning. BNP
      levels of the cases which were determined to have increased cTnI levels showing
      myocardial injury increased as well. BNP can show myocardial injury and its
      severity in acute CO poisoning.

PMID- 27049271
TI  - Evaluation of serum vitamin D levels in patients with X syndrome.
AB  - OBJECTIVE: Cardiac X syndrome is defined in patients with normal coronary
      angiogram who has typical chest pain and objective myocardial ischemia evidence.
      Recent studies have evaluated the association between vitamin D deficiency (vit D
      def) and cardiovascular diseases. Our aim of this study was to compare serum vit
      D levels in patients with syndrome X and controls. PATIENTS AND METHODS: We
      included 66 patients (49 women, 17 men) with syndrome X and 47 (30 women, 17 men)
      healthy controls. All of the patients' demographic features, laboratory analysis
      and medications are recorded. Vit D is measured quantitatively by paramagnetic
      particle chemiluminescence method. RESULTS: Mean age of the syndrome X group was
      higher than controls (56 +/- 9.2 vs. 49 +/- 9.6 years p < 0.001). Body mass index
      was higher in the patient group than controls (31.2 +/- 5.6 vs. 29.1 +/- 4.7
      kg/m2 p: 0.011). Vit D levels were significantly lower in the syndrome X group
      than controls (6 +/- 5.2 vs. 11.9 +/- 7 ng/ml, p < 0.001). Parathormone levels
      were significantly higher in the syndrome X group than the control group (38.3 +/
      23.4 vs. 28 +/- 17.2 pg/ml, p: 0.014). hsCRP levels were higher in the syndrome
      X group than controls (3.1 +/- 5.4 vs. 1.8 +/- 2.4 mg/L, p: 0.042). CONCLUSIONS:
      Our study demonstrated significantly lower vit D levels in patients with CSX.
      This finding is correlated with previous studies showing an inverse correlation
      with lower serum vit D levels and different types of cardiovascular diseases. Vit
      D def may be a risk factor for syndrome X. Vit D def related increased
      inflammation may lead to the development of endothelial dysfunction and
      microvascular angina.

PMID- 27049272
TI  - Screening of coronary artery anomalies in 11,707 patients reveals that the radial
      approach is safe for cannulating coronary anomalies.
AB  - OBJECTIVE: This study evaluated the transradial approach for its ability to
      diagnose coronary artery anomalies, its requirement for catheter usage, the
      number of images obtained and fluoroscopy time required. PATIENTS AND METHODS: A
      total of 11,707 patients' coronary angiograph reports from January 2009 to
      January 2016 were evaluated with 179 patients identified as having coronary
      artery anomalies. Subsequent analyses compared patients' access sites with
      multiple angiographic parameters, including the number of images obtained,
      catheters used, and the fluoroscopy time required. RESULTSesults: The frequency
      of coronary artery anomalies identified by angiographies was 0.015%. Coronary
      anomalies were detected by transradial access (TRA) in 133 patients and by
      transfemoral access (TFA) in 46 patients. The most common anomaly was in the
      right coronary artery originating from the left sinus Valsalva (71 patients;
      39.2%). The fluoroscopy times required and the number of catheters used was
      similar between the TRA and TFA groups (p = 0.887 and 0.302, respectively) while
      the number of images obtained during coronary angiographies was higher in the TFA
      group (p = 0.021). CONCLUSIONS: TRA is safe and effective for cannulation and the
      diagnosis of congenital coronary artery anomalies.

PMID- 27049273
TI  - Supraglottic jet oxygenation and ventilation during colonoscopy under monitored
      anesthesia care: a controlled randomized clinical trial.
AB  - OBJECTIVE: Supraglottic jet oxygenation and ventilation may provide active pulse
      oxygenation and ventilation in patients with respiratory suppression. This
      randomized controlled clinical study was designed to determine the efficacy and
      safety of supraglottic jet oxygenation/ventilation during monitored anesthesia
      care (MAC) by intravenous (IV) infusion of propofol in patients undergoing
      colonoscopy. PATIENTS AND METHODS: Forty-nine adult patients receiving
      colonoscopy were randomly divided into two groups: the control group with passive
      oxygen supply from regular nasal cannula (N = 24) and the supraglottic jet
      oxygenation/ventilation (SJV) group with active pulse oxygen supply and
      ventilation using a manual jet ventilator (N = 25). MAC was induced and
      maintained by intravenous injection of propofol. HR, ECG, BP, SaO2 were
      continuously monitored during and 1 hour after the procedure. RESULTS:
      Demographic characteristics were similar in height, weight, age and BMI (Body
      Mass Index) between the two groups. Compared to the control group, the SJV group
      had similar averaged lowest SaO2, but highest SaO2 in SJV group were
      significantly lower during operation (p = 0.01). The proportion of maximum chest
      rise movement were increased significantly in SJV group (p = 0.03) compared with
      control group. Demographic characteristics were similar in the times needed to
      use facial mask ventilation, percentage of time to maintain SaO2 above 96%,
      average PetCO2 during the procedure, or complications between the two groups.
      CONCLUSIONS: SJV can provide adequate oxygenation/ventilation during monitored
      anesthesia care and convenient monitoring for patients' breath, without
      complications.

PMID- 27049274
TI  - Deliberate drug poisonings admitted to an emergency department in Paris area - a
      descriptive study and assessment of risk factors for intensive care admission.
AB  - OBJECTIVE: Each year, approximately 165,000 poisonings are managed in the
      emergency departments (ED) in France. We performed a descriptive analysis of self
      poisoned patients admitted to a university hospital ED in the Paris metropolitan
      area (France) aimed at investigating their outcome and the risk factors for
      transfer to the intensive care unit (ICU). PATIENTS AND METHODS: We
      retrospectively reviewed patients' records and performed multivariate logistic
      regression analysis to identify risk factors for ICU admission. RESULTS: During 4
      years, 882 self-poisoned patients (median age, 38 years [IQR, 26-47]; sex-ratio,
      1M/3F) were admitted to the ED, representing 0.7% of all referred patients.
      Poisonings mainly resulted from multidrug exposures (53%), including
      benzodiazepines (78%), serotonin reuptake inhibitors (17%), acetaminophen (13%),
      antipsychotics (9.5%), imidazopyridines (9.5%), antihypertensive drugs (3%), and
      polycyclic antidepressants (1.3%). Ethanol was involved in 20% of the exposures.
      Patients were briefly (<24h) monitored in the ED (55%), transferred to the
      psychiatric department (30%), medical ward (2%) or ICU (6%), and took an
      irregular discharge (7%). Among the patients transferred to the ICU, 25% were
      mechanically ventilated and only one died. Risk factors for ICU admission
      included antihypertensive (Odds ratio (OR), 40.6; 95%-confidence interval (CI),
      7.5-221.9) or antipsychotic drug ingestion (OR, 5.3; CI, 2.0-14.4), male gender
      (OR, 3.3; CI, 1.30-8.8), and consciousness impairment (OR, 2.1; CI, 1.8-2.5 per
      point lost in Glasgow coma score). CONCLUSIONS: Deliberate drug exposure
      represents a frequent cause of ED admission. Psychotropic drugs are most commonly
      involved. Transfer to the ICU is rare and predicted by male gender, drug class,
      and coma depth.

PMID- 27049275
TI  - Magnesium sulfate micro air pump suction for bronchiolitis treatment in infants
      under two years old.
AB  - OBJECTIVE: To investigate the efficiency, clinical effects and nursing methods
      related to the use of magnesium sulfate micro air pump suction for treating
      infants under two years old suffering from bronchiolitis. PATIENTS AND METHODS:
      From January 2014 to September 2014, ninety-six infants with capillary bronchitis
      were enrolled. Patients were randomly divided into two groups: experimental group
      (n=49) and control group (n=47). All patients went through conventional anti
      inflammatory therapy. Based on this, infants in the control group were
      additionally treated with intravenous drip of magnesium sulfate while patients in
      the experimental group were treated with magnesium sulfate micro air pump
      suction. We recorded all changes in blood gas and clinical scores, the residence
      time of symptoms and signs of bronchiolitis, and hospitalization time. Results
      obtained on clinical effects and adverse reactions were compared and analyzed.
      RESULTS: The Variations of PaO2, PaCO2, SaO2 before treatment in both groups did
      not show any statistically significant differences (p>0.05); while after
      treatment analyses demonstrated that in both groups we had an increase in PaO2
      and SaO2 and a decrease in PaCO2. The increase in PaO2 and SaO2 values were more
      pronounced while the decrease observed in PaCO2 was more significant in our
      experimental group. The total effective rate was significantly higher while the
      total adverse reaction rate, the resolution time of clinical symptoms and
      hospitalization time were significantly lower in our experimental group.
      CONCLUSIONS: Magnesium sulfate micro air pump suction was safe and effective in
      treating with bronchiolitis of infants below 2 years old, and its adverse
      reaction rate was low, nursing procedure was simple, and nursing difficulty level
      was low.

PMID- 27049276
TI  - Statin ameliorates endothelial dysfunction and insulin resistance in Tibet women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a disorder characterized by
      hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In Tibet
      population, little is known about the correlation between PCOS and endothelial
      function and insulin resistance. In this study, we investigated the efficacy of
      simvastatin on ameliorating endothelial dysfunction and insulin resistance in
      Tibet patients with PCOS. PATIENTS AND METHODS: A group of 21 PCOS women was
      compared with 21 age-paired controls for blood pressure, body mass index (BMI),
      lipids, glucose and insulin levels. Plasma ET-1 was quantitated using a
      commercially available ELISA kits. The invasive vascular endothelial function was
      evaluated through the measurement of brachial artery flow-mediated dilation (FMD)
      in the fasting state using high-resolution B-mode ultrasound and ankle-brachial
      index (ABI) by using a blood pressure cuff and a Doppler instrument. RESULTS:
      PCOS women had higher BMI (p < 0.05), blood pressure (p < 0.05), cholesterol (p <
      0.05), triglyceride (p < 0.05), LDL cholesterol (p < 0.05) and lower HDL
      cholesterol (p < 0.05). Fasting insulin (p < 0.001) and 2-hour plasma glucose (p
      < 0.001) of PCOS were also found to be higher than that of controls. HOMA-IR of
      PCOS was calculated to be much higher than that of the control group (p < 0.001).
      ET-1 levels were significantly higher in the PCOS women compared with the control
      group (p < 0.001). FMD and ABI were impaired in the PCOS group when compared with
      the controls (p < 0.001). After simvastatin intervention for 6 months, FMD, ABI,
      HOMA-IR, lipid profile, BMI were ameliorated in PCOS women. Also, FMD, ABI, HOMA
      IR, lipid profile were nearly normalized in PCOS women after statin treatment
      compared with the control women. Tibet PCOS patients present a clustering of
      atherosclerosis risk factors (obesity, adverse lipid profile, hypertension and
      hyperglycemia) and more prevalent in insulin resistance and endothelial
      dysfunction than non-PCOS women. CONCLUSIONS: The endothelial function and
      insulin resistance of PCOS patients were ameliorated CONCLUSIONS: The endothelial
      function and insulin resistance of PCOS patients were ameliorated after statin
      administration.

PMID- 27049277
TI  - Protective effects of thymoquinone and alpha-tocopherol on the sciatic nerve and
      femoral muscle due to lower limb ischemia-reperfusion injury.
AB  - OBJECTIVE: Thymoquinone (TQ) is an antioxidant and anti-apoptotic substance found
      in the Nigella sativa plant. Alpha-tocopherol (alpha-TP) is a potent antioxidant.
      We aimed to determine whether or not TQ and TP have a protective effect against
      lower limb ischemia-reperfusion (IR) injury of muscle and the sciatic nerve.
      MATERIALS AND METHODS: A single dose of TQ 25 mg/kg was given intraperitoneally
      to the TQ group, a single dose of alpha-TP 200 mg/kg was given intraperitoneally
      to the alpha-TP group. IR was performed for 45 minutes after the drugs'
      applications. RESULTS: While serum levels of malondialdehyde (MDA) and
      interleukin-6 (IL-6) of the IR group were significantly higher than those of the
      TQ plus alpha-TP, TQ and alpha-TP groups (p<0.001, p<0.001, p=0.008,
      respectively) and IL-6 (all p<0.001), the reduced glutathione (GSH) level of the
      IR group was lower than that of the other three groups. While neuronal nitric
      oxide synthase activity of nerve tissues of the IR group was significantly lower
      than that of the TQ plus alpha-TP group, the muscle tissue caspase-3 activity was
      higher than that of the TQ plus alpha-TP group. CONCLUSIONS: Administration of TQ
      plus alpha-TP may strongly protect muscle and nerve tissues against IR injury via
      their synergistic effects.

PMID- 27049278
TI  - Resveratrol attenuates senescence of adipose-derived mesenchymal stem cells and
      restores their paracrine effects on promoting insulin secretion of INS-1 cells
      through Pim-1.
AB  - OBJECTIVE: The paracrine effects of mesenchymal stem cells (MSCs) were weakened
      during aging. This study explored whether resveratrol can attenuate senescence of
      adipose-derived MSCs (ADMSCs) and whether Pim-1 is involved in resveratrol's
      effect on paracrine of ADMSCs and insulin secretion of INS-1 cells. MATERIALS AND
      METHODS: CCK-8 assay and SA-b-gal assay were performed to test the protective
      effect of resveratrol on senescent models. QRT-PCR and western blot analysis were
      performed to analyze of senescence- and beta-cell associated genes. QRT-PCR and
      ELISA analysis was performed to test telomere length and activity.
      Immunofluorescence and ELISA assay were performed to assess the paracrine effects
      on promoting insulin secretion of INS-1 cells. RESULTS: Resveratrol could protect
      ADMSCs from H2O2 and D-glucose-induced senescence and also attenuate senescence
      in long-term cultured ADMSCs in vitro. In addition, resveratrol attenuated H2O2
      induced higher expression of senescence-associated genes, including P53, P21,
      Cyclin D1, IL-6 and MMP1, but increased the expression of Sirt1, a well-known
      anti-senescence gene. Resveratrol significantly enhanced Pim-1 expression in
      aging ADMSCs through PI3K/AKT signal pathway. The conditioned medium (CM) of
      ADMSCs enhanced insulin secretion and expression of the key genes for beta-cell
      function including TFAM, PDX1, GLUT2 and HNF-1alpha via Pim-1. INS-1 cells with
      Pim-1 knockdown had decreased insulin secretion. CONCLUSIONS: This study firstly
      reported that resveratrol has a protective effect on senescence of ADMSCs and can
      preserve the paracrine effect of the ADMSCs on promoting insulin secretion of INS
      1 cells via Pim-1. Therefore, it might be a promising adjuvant agent for future
      MSCs based therapy.

PMID- 27049279
TI  - Skin whitening capability of shikimic acid pathway compound.
AB  - OBJECTIVE: To examine the skin whitening capabilities of shikimic acid pathway
      compounds and find the most effective molecule to be used as the active
      ingredient for skin whitening products. MATERIALS AND METHODS: Skin whitening is
      the practice of using chemical substances to lighten skin tone by the lessening
      the concentration of melanin. The whitening efficacy of shikimic acid pathway
      compounds was evaluated. Eight compounds in the shikimic acid pathway were chosen
      for this study: benzoic acid, p-coumaric acid, vanillic acid, syringic acid,
      quinic acid, shikimic acid, orcinol monohydrate, and phenyl pyruvic acid. We
      measured the tyrosinase inhibitory capacity of the compounds in the animal model
      of zebrafish and also evaluated the compounds' anti-oxidant activities using the
      DPPH radical scavenging, and ABTS+ free radical scavenging tests. Compounds'
      cytotoxicity effects were also evaluated. RESULTS: Amongst eight shikimic acid
      pathway compounds used in this study, shikimic acid was the most potent
      tyrosinase-inhibitor and the most efficient compound to be used as an active
      ingredient for skin whitening. Shikimic acid revealed a good radical scavenging
      activity (RAS) with low cell toxicity. CONCLUSIONS: Promising results obtained in
      this study may open a new window of opportunity to introduce another compound to
      be used in the skin-whiting cosmetics industry.

PMID- 27049280
TI  - Low dose etanercept treatment for maintenance of clinical remission in ankylosing
      spondylitis.
AB  - OBJECTIVES: To investigate the efficacy and safety of low-dose etanercept
      treatment after clinical remission of ankylosing spondylitis (AS) in the real
      world. METHODS: Data on 134 AS patients who were treated with etanercept for more
      than 12 months and achieved clinical remission (BASDAI<4 and CRP<0.5 mg/dL) were
      extracted from a large single centre registry. Drug survival and incidence of
      adverse events in 100 patients who reduced the dose during follow up (low-dose
      group) were compared with 34 patients who maintained the initial dose (standard
      dose group). For minimisation of selection bias between the two groups, the same
      analyses were performed in a propensity score-matched population. RESULTS: Both
      groups showed similar BASDAI score and CRP levels during the follow-up. Drug
      survivals between the two groups were also comparable up to 4 years (vs. standard
      dose group, adjusted HR=0.472, 95% CI 0.155-1.435). The same analysis performed
      after propensity score-matching showed concordant result. The incidence of
      injection site reactions in the low-dose group was significantly lower, and the
      incidence of other adverse events showed no differences between the two groups.
      In the low-dose group, dose reduction after more than 24 weeks of standard-dose
      treatment was associated with longer drug survival (adjusted HR=0.261, 95% CI
      0.084-0.809). CONCLUSIONS: Low-dose etanercept treatment after achieving clinical
      remission can be an alternative treatment option in terms of its comparable long
      term efficacy and favourable safety in AS. More than 24 weeks of standard-dose
      treatment before dose reduction may be beneficial for longer drug survival in
      this strategy.

PMID- 27049281
TI  - Research capacity in Africa-will the sun rise again?

PMID- 27049282
TI  - Description and plasmid characterization of the qnrD determinant in Proteeae in
      Wenzhou, Southern China.
AB  - BACKGROUND/PURPOSE: Only limited information is available about the detailed
      characteristics of qnrD, a plasmid-mediated quinolone resistance (PMQR) gene.
      This study aimed to understand the distribution of qnrD and the characterization
      of qnrD-carrying plasmids in Proteeae. METHODS: The distribution of qnrD genes
      was investigated by polymerase chain reaction (PCR) amplification in 203
      consecutive nonduplicate clinical isolates of Proteeae collected from inpatients
      at the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
      The minimum inhibitory concentrations (MICs) of antibiotics were measured by agar
      dilution method and other PMQR determinants were also determined by PCR. qnrD was
      positioned via Southern hybridization and the transferability of qnrD-carrying
      plasmids was achieved by conjugation experiment. The genetic environment of qnrD
      was investigated by sequencing, and chromosomal polymorphism for qnrD-positive
      strains was analyzed by pulsed-field gel electrophoresis (PFGE). RESULTS: Forty
      strains carried qnrD, showing decreased fluoroquinolone susceptibility or low
      level fluoroquinolone resistance. qnrD was encoded on the plasmid of about 2.7 kb
      or 5.2 kb in length, which cannot be transferred by liquid conjugation or filter
      mating, but can be successfully transferred by transduction. The transformants
      showed 62.5-300-fold increases in the MICs of quinolones compared with the
      recipient. The plasmids carrying qnrD showed a high similarity with that of
      Providencia spp. and Proteus vulgaris. PFGE analysis demonstrated that these
      isolates were divergent and not clone related. CONCLUSION: qnrD could have
      originated from Proteeae or presented in these bacteria as a reservoir;
      furthermore, qnrD could be transferred and spread within the same or across
      different bacterial species if the plasmids acquired mobile elements under
      antimicrobial selective pressures.

PMID- 27049283
TI  - Self-assembled nanofiber hydrogels for mechanoresponsive therapeutic anti
      TNFalpha antibody delivery.
AB  - Low molecular weight hydrogels, prepared from glycosyl-nucleoside-lipid
      amphiphiles, exhibit shear-thinning behaviour and reversible thermally- and
      mechanically-triggered sol-gel transitions. Using mechanical shear stimulation,
      the release of entrapped anti-TNFalpha increases and the released anti-TNFalpha
      demonstrates efficacy in in vitro neutralization bioassays. Delivery of anti
      TNFalpha is of general interest and broad medicinal utility for treating
      autoimmune diseases such as rheumatoid arthritis. 

PMID- 27049284
TI  - Dual Antiplatelet Therapy Beyond 1 Year Postinfarction: The Time Has Come and
      We're Beginning to Know Who Will Benefit.

PMID- 27049285
TI  - Neprilysin Plasma Concentrations: A New Prognostic Marker in Heart Failure.

PMID- 27049286
TI  - Cu diffusion as an alternative method for nanopatterned CuTCNQ film growth.
AB  - In this paper we show by means of 'in situ' x-ray diffraction studies that CuTCNQ
      formation from Cu(solid)-TCNQ(solid tetracyanoquinodimethane) goes through Cu
      diffusion at room temperature. The film quality depends on the TCNQ evaporation
      rate. At low evaporation rate we get a single phase-I CuTCNQ film very well
      crystallized and well oriented. The film has a CuTCNQ(0 2 0) orientation. The
      film is formed by CuTCNQ nanorods of a very homogeneous size. The film
      homogeneity has also been seen by atomic force microscopy (AFM). The electronic
      properties of the film have been measured by x-ray photoelectron spectroscopy
      (XPS) and ultra-violet photoelectron spectroscopy (UPS). Thus, the Cu-diffusion
      method has arisen as a very simple, clean and efficient method to grow localized
      CuTCNQ nanorods on Cu, opening up new insights for technological applications. 

PMID- 27049287
TI  - Corrigendum to "Epidermal growth factor increases LRF/Pokemon expression in human
      prostate cancer cells" [Exp. Mol. Pathol. 91 (2011) 496-501].

PMID- 27049288
TI  - Retraction notice to "Ski diminishes TGF-beta1-induced myofibroblast phenotype
      via up-regulating Meox2 expression".

PMID- 27049289
TI  - The effect of phosphatidylinositol-3 kinase inhibition on matrix
      metalloproteinase-9 and reactive oxygen species release from chronic obstructive
      pulmonary disease neutrophils.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterised by
      increased neutrophilic inflammation. A potential novel anti-inflammatory target
      in COPD is phosphatidylinositol-3 kinase (PI3 kinase), which targets neutrophil
      function. This study evaluated the effects of selective PI3Kdelta inhibition on
      COPD blood and sputum neutrophils both in the stable state and during
      exacerbations. METHODS: Blood and sputum neutrophils from stable and exacerbating
      COPD patients were cultured with the corticosteroid dexamethasone, a pan PI3
      kinase inhibitor (ZSTK474), a delta selective PI3 kinase inhibitor (GSK045) and a
      p38 mitogen activated protein (MAP) kinase inhibitor (BIRB 796); matrix
      metalloproteinase (MMP)-9 and reactive oxygen species (ROS) release were
      analysed. RESULTS: PI3Kdelta inhibition significantly reduced MMP-9,
      intracellular ROS and extracellular ROS release from blood neutrophils (45.6%,
      30.1% and 47.4% respectively; p<0.05) and intracellular ROS release from sputum
      neutrophils (16.6%; p<0.05) in stable patients. PI3Kdelta selective inhibition
      significantly reduced stimulated MMP-9 (36.4%; p<0.05) and unstimulated and
      stimulated ROS release (12.6 and 26.7%; p<0.05) from blood neutrophils from
      exacerbating patients. The effects of the p38 MAP kinase inhibitor and
      dexamethasone in these experiments were generally lower than PI3Kdelta
      inhibition. CONCLUSION: PI3Kdelta selective inhibition is a potential strategy
      for targeting glucocorticoid insensitive MMP-9 and ROS secretion from COPD
      neutrophils, both in the stable state and during exacerbations.

PMID- 27049290
TI  - Relationship between PCO2 and unfavorable outcome in infants with moderate-to
      severe hypoxic ischemic encephalopathy.
AB  - BACKGROUND: Abnormal PCO2 is common in infants with hypoxic ischemic
      encephalopathy (HIE). The objective was to determine whether hypocapnia was
      independently associated with unfavorable outcome (death or severe
      neurodevelopmental disability at 18 mo) in infants with moderate-to-severe HIE.
      METHODS: This was a post hoc analysis of the CoolCap Study in which infants were
      randomized to head cooling or standard care. Blood gases were measured at
      prespecified times after randomization. PCO2 and follow-up data were available
      for 196 of 234 infants. Analyses were performed to investigate the relationship
      between hypocapnia in the first 72 h after randomization and unfavorable outcome.
      RESULTS: After adjusting for pH, amplitude-integrated electroencephalogram
      background and seizures, birth weight, Apgar score at 5 min, cooling status, and
      Sarnat stage, PCO2 was inversely associated with unfavorable outcome (P < 0.001).
      The probability of unfavorable outcome was 0.20 +/- 0.1 (point estimate +/- SE),
      0.53 +/- 0.23 and 0.89 +/- 0.16 for a PCO2 of 40, 30, and 20 mm Hg respectively
      and was greater in infants with severe HIE than with moderate HIE. CONCLUSIONS:
      Hypocapnia in infants with moderate-to-severe HIE was independently associated
      with unfavorable outcome. Future studies of controlled normocapnia will be
      important.

PMID- 27049291
TI  - Paneth cells in the developing gut: when do they arise and when are they immune
      competent?
AB  - BACKGROUND: Little is known about the perinatal development of Paneth cells (PCs)
      during gestation and the relation with necrotizing enterocolitis (NEC). We aimed
      to investigate when PCs arise and when they become immune competent during
      gestation. METHODS: We included 57 samples of ileum tissue of fetuses/infants
      with a gestional age (GA) between 9 and 40 wk taken as part of a standard autopsy
      procedure. Hematoxylin-eosin staining and anti-human defensin 5
      immunohistochemistry were performed. We performed a semi-quantitative assessment
      of (immune-competent) PC numbers per 10 crypts per tissue section per GA.
      RESULTS: The number of PCs and the number of immune-competent PCs increased with
      increasing GA (Spearman's rho = 0.41, P = 0.002 and rho = 0.61, P < 0.001,
      respectively). Whereas significantly higher PC numbers were observed after 37 wk
      gestation (median 7, range 0-12) compared to preterm infants (median 0, range 0
      15; P = 0.002), we counted higher numbers of immune-competent PCs already in
      infants with GA above 29 wk (median 6, range 0-18) compared to infants with GA
      under 29 wk (median 2, range 0-9; P < 0.001). CONCLUSION: The significant
      increase of immune-competent PCs starting from a GA of 29 wk mimics the rise in
      incidence of NEC during a similar postmenstrual age in preterm infants.

PMID- 27049293
TI  - Non-invasive chemically specific measurement of subsurface temperature in
      biological tissues using surface-enhanced spatially offset Raman spectroscopy.
AB  - Here we demonstrate for the first time the viability of characterising non
      invasively the subsurface temperature of SERS nanoparticles embedded within
      biological tissues using spatially offset Raman spectroscopy (SORS). The proposed
      analytical method (T-SESORS) is applicable in general to diffusely scattering
      (turbid) media and features high sensitivity and high chemical selectivity. The
      method relies on monitoring the Stokes and anti-Stokes bands of SERS
      nanoparticles in depth using SORS. The approach has been conceptually
      demonstrated using a SORS variant, transmission Raman spectroscopy (TRS), by
      measuring subsurface temperatures within a slab of porcine tissue (5 mm thick).
      Root-mean-square errors (RMSEs) of 0.20  degrees C were achieved when measuring
      temperatures over ranges between 25 and 44  degrees C. This unique capability
      complements the array of existing, predominantly surface-based, temperature
      monitoring techniques. It expands on a previously demonstrated SORS temperature
      monitoring capability by adding extra sensitivity stemming from SERS to low
      concentration analytes. The technique paves the way for a wide range of
      applications including subsurface, chemical-specific, non-invasive temperature
      analysis within turbid translucent media including: the human body, subsurface
      monitoring of chemical (e.g. catalytic) processes in manufacture quality and
      process control and research. Additionally, the method opens prospects for
      control of thermal treatment of cancer in vivo with direct non-invasive feedback
      on the temperature of mediating plasmonic nanoparticles.

PMID- 27049292
TI  - Neonatal growth restriction-related leptin deficiency enhances leptin-triggered
      sympathetic activation and central angiotensin II receptor-dependent stress
      evoked hypertension.
AB  - BACKGROUND: Neonatal growth restriction (nGR) leads to leptin deficiency and
      increases the risk of hypertension. Previous studies have shown nGR-related
      hypertension is normalized by neonatal leptin (nLep) and exacerbated by
      psychological stress. With recent studies linking leptin and angiotensin
      signaling, we hypothesized that nGR-induced nLep deficiency increases adult
      leptin sensitivity; leading to leptin- or stress-induced hypertension, through a
      pathway involving central angiotensin II type 1 receptors. METHODS: We randomized
      mice with incipient nGR, by virtue of their presence in large litters, to vehicle
      or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and
      arterial pressure were monitored at baseline, during intracerebroventricular
      losartan infusion and during systemic leptin administration. RESULTS: nGR
      increased leptin-triggered renal sympathetic activation and hypertension with
      increased leptin receptor expression in the arcuate nucleus of the hypothalamus;
      all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had
      stress-related hyperphagia and hypertension, but only the stress hypertension was
      blocked by central losartan infusion. CONCLUSION: nGR leads to stress
      hypertension through a pathway that involves central angiotensin II receptors,
      and nGR-associated leptin deficiency increases leptin-triggered hypertension in
      adulthood. These data suggest potential roles for preservation of neonatal growth
      and nLep supplementation in the prevention of nGR-related hypertension.

PMID- 27049294
TI  - Identification and evaluation of magnolol and chrysophanol as the principle
      protein tyrosine phosphatase-1B inhibitory compounds in a Kampo medicine,
      Masiningan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Masiningan is a traditional medicine consisting
      of six crude drugs that have been used for treating constipation and diabetes
      mellitus in both Japan and China. Masiningan has been reported to have
      significant PTP1B inhibitory activity and to affect cells in the insulin
      signaling pathway. The aim of the present study is to identify the PTP1B
      inhibitory compounds in Masiningan. MATERIALS AND METHODS: Bioactivity peaks were
      identified by analytical HPLC profiling and PTP1B inhibitory activity profiling
      of sub-fractions from Masiningan extract. The bioactive compounds were isolated
      by tracking two identified bioactive peaks, and the chemical structures were
      determined by spectroscopic analyses. The bioactive compounds were further
      investigated for their inhibitory effect against PTP1B by enzymatic kinetic
      analysis, molecular docking simulation, inhibitory selectivity against other
      PTPs, and cellular activity in the insulin signal transduction pathway. RESULTS:
      From Masiningan, magnolol (1) and chrysophanol (2) were isolated as compounds
      that exhibited significant dose-dependent inhibitory activities against PTP1B,
      with IC50 values of 24.6 and 12.3MUM, respectively. Kinetic analysis revealed
      that 1 is a non-competitive and that 2 is a competitive PTP1B inhibitor. In the
      molecular docking simulation, compound 2 was stably positioned in the active
      pocket of PTP1B, and the CDOCKER energy was calculated to be 24.3411kcal/mol.
      Both compounds demonstrated remarkably high selectivity against four PTPs and
      revealed cellular activity against the insulin signal transduction pathway.
      CONCLUSIONS: Magnolol (1) and chrysophanol (2) were identified as the principle
      PTP1B inhibitory active compounds in Masiningan, and their actions were
      investigated in detail. These findings demonstrated the effectiveness of
      Masiningan on diabetes mellitus through the inhibition of PTP1B at a molecular
      level as well as the potential of magnolol (1) and chrysophanol (2) as lead
      compounds in future anti-diabetes drug development.

PMID- 27049296
TI  - Plasmon-mediated chemical surface functionalization at the nanoscale.
AB  - Controlling the surface grafting of species at the nanoscale remains a major
      challenge, likely to generate many opportunities in materials science. In this
      work, we propose an original strategy for chemical surface functionalization at
      the nanoscale, taking advantage of localized surface plasmon (LSP) excitation.
      The surface functionalization is demonstrated through aryl film grafting (derived
      from a diazonium salt), covalently bonded at the surface of gold lithographic
      nanostripes. The aryl film is specifically grafted in areas of maximum near field
      enhancement, as confirmed by numerical calculation based on the discrete dipole
      approximation method. The energy of the incident light and the LSP wavelength are
      shown to be crucial parameters to monitor the aryl film thickness of up to ~30
      nm. This robust and versatile strategy opens up exciting prospects for the
      nanoscale confinement of functional layers on surfaces, which should be
      particularly interesting for molecular sensing or nanooptics. 

PMID- 27049295
TI  - Astragalus polysaccharides decrease muscle wasting through Akt/mTOR, ubiquitin
      proteasome and autophagy signalling in 5/6 nephrectomised rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Existing evidences suggest that Radix Astragali
      and its polysaccharides composition (APS) can improve muscle mass, but the
      mechanisms need more research. AIM OF THE STUDY: In this study, we aimed to
      examine the effects of APS on muscle wasting at molecular level in 5/6
      nephrectomised rats. MATERIALS AND METHODS: We performed 5/6 nephrectomy or sham
      operation in 160 6-week-old Sprague-Dawley rats, and feed animals with or without
      2% APS for 155 days. After treatment, we compared the change of weight, muscle
      fibre, protein metabolism, pro-inflammatory factors (TNF-alpha, IL-15, CRP) and
      oxidative factors (MDA, SOD) among each group. In addition, we detected the
      Akt/mTOR, ubiquitin proteasome, autophagy signalling and AA transporters in vivo
      and in vitro. RESULTS: Data in vivo show 2% APS could alleviate weight loss and
      improve protein metabolism in nephrectomised rats. The levels of serum pro
      inflammatory factors and oxidative factors were restored by APS treatment. In
      molecular levels, APS restored Akt/mTOR, MAFbx, MuRF1, Atg7, LC3B-II/LC3B-I and
      SLC38A2 which changed in nephrectomised rats. Data in vitro show the optimal dose
      of APS is 0.2mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2mg/mL APS on
      atrophy and autophagy. CONCLUSIONS: Our results suggested APS could improve
      muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling,
      and SLC38A2 may be one of potential targets.

PMID- 27049298
TI  - Are You Ready for Maintenance of Certification Self-Assessment 2.0?: It's Here,
      It's Cheaper, and It's Easier.

PMID- 27049297
TI  - Prevalence and Metrics Distribution of Ideal Cardiovascular Health: A Population
      based, Cross-sectional Study in Rural China.
AB  - BACKGROUND: The American Heart Association (AHA) introduced definitions of
      "ideal," "intermediate," and "poor" cardiovascular health (CVH) based on seven
      cardiovascular health metrics (smoking, body mass index, physical activity, diet
      score, total cholesterol, blood pressure, and fasting glucose). This study used
      this construct to assess the prevalence and metric distribution of CVH in a rural
      population with traditional lifestyles and investigate the relationship of CVH
      with socio-demographic characteristics of participants. METHODS: From January
      2012 to August 2013, a representative sample of 11,113 adults (mean age 53.8+/
      10.6 years; 53.8% women) was enrolled from a rural population in Northeast China
      using a multi-stage, stratified random cluster-sampling scheme. RESULTS:
      According to the adjusted AHA criteria for CVH health metrics, there was 0.1%
      prevalence of ideal CVH (all seven health metrics at ideal levels), 11.7% of
      intermediate CVH (at least one health metric at intermediate level, but no poor
      health metrics), and 88.2% of poor CVH (at least one of seven health metrics at
      poor level). Women and young/middle-aged adults were more likely to have all of
      the ideal CVH metrics, behaviours, factors and CVH status. CONCLUSIONS: Our study
      showed extremely low (0.1%) prevalence of ideal CVH in the rural population of
      northeast China. The poor CVH status, particularly among men and older
      individuals, underscores the need for urgent action on modifiable risk factors,
      especially blood pressure and smoking.

PMID- 27049299
TI  - Zero-inflated negative binomial mixed model: an application to two microbial
      organisms important in oesophagitis.
AB  - Altered microbial communities are thought to play an important role in
      eosinophilic oesophagitis, an allergic inflammatory condition of the oesophagus.
      Identification of the majority of organisms present in human-associated microbial
      communities is feasible with the advent of high throughput sequencing technology.
      However, these data consist of non-negative, highly skewed sequence counts with a
      large proportion of zeros. In addition, hierarchical study designs are often
      performed with repeated measurements or multiple samples collected from the same
      subject, thus requiring approaches to account for within-subject variation, yet
      only a small number of microbiota studies have applied hierarchical regression
      models. In this paper, we describe and illustrate the use of a hierarchical
      regression-based approach to evaluate multiple factors for a small number of
      organisms individually. More specifically, the zero-inflated negative binomial
      mixed model with random effects in both the count and zero-inflated parts is
      applied to evaluate associations with disease state while adjusting for potential
      confounders for two organisms of interest from a study of human microbiota
      sequence data in oesophagitis.

PMID- 27049300
TI  - Physical Activity Frequency on the 10-Year Acute Coronary Syndrome (ACS)
      Prognosis; The Interaction With Cardiovascular Disease History and Diabetes
      Mellitus: The GREECS Observational Study.
AB  - The association between physical activity, diabetes mellitus (DM), and long-term
      acute coronary syndrome (ACS) prognosis was evaluated. The GREECS study included
      2,172 consecutive ACS patients from six Greek hospitals (2003-2004). In 2013
      2014, a 10-year follow up was performed with 1,918 patients. Physical activity
      was categorized in never, rarely (monthly basis), 1-2 and >= 3 times/week. Multi
      adjusted analysis revealed that 1-2 and >= 3 times/week vs. no physical activity
      had a protective effect on ACS incidence (OR = 0.63 95% CI 0.38, 1.05) and (OR =
      0.63 95% CI 0.40, 0.99) respectively, only in patients without prior baseline CVD
      event. In a subgroup analysis, with DM as strata in these patients, engagement in
      physical activity (i.e., 1-2 times/week) had a significant protective effect
      among patients with diabetes (OR = 0.51, 95% CI 0.27, 0.96, p = .037). These
      findings revealed the beneficial role of exercise in secondary ACS prevention,
      even in DM patients. Public health-oriented policies should incorporate regular
      physical activity as a key protective factor in disease prognosis.

PMID- 27049301
TI  - Whole-exome sequencing in an isolated population from the Dalmatian island of
      Vis.
AB  - We have whole-exome sequenced 176 individuals from the isolated population of the
      island of Vis in Croatia in order to describe exonic variation architecture. We
      found 290 577 single nucleotide variants (SNVs), 65% of which are singletons, low
      frequency or rare variants. A total of 25 430 (9%) SNVs are novel, previously not
      catalogued in NHLBI GO Exome Sequencing Project, UK10K-Generation Scotland,
      1000Genomes Project, ExAC or NCBI Reference Assembly dbSNP. The majority of these
      variants (76%) are singletons. Comparable to data obtained from UK10K-Generation
      Scotland that were sequenced and analysed using the same protocols, we detected
      an enrichment of potentially damaging variants (non-synonymous and loss-of
      function) in the low frequency and common variant categories. On average 115
      (range 93-140) genotypes with loss-of-function variants, 23 (15-34) of which were
      homozygous, were identified per person. The landscape of loss-of-function
      variants across an exome revealed that variants mainly accumulated in genes on
      the xenobiotic-related pathways, of which majority coded for enzymes. The
      frequency of loss-of-function variants was additionally increased in Vis runs of
      homozygosity regions where variants mainly affected signalling pathways. This
      work confirms the isolate status of Vis population by means of whole-exome
      sequence and reveals the pattern of loss-of-function mutations, which resembles
      the trails of adaptive evolution that were found in other species. By cataloguing
      the exomic variants and describing the allelic structure of the Vis population,
      this study will serve as a valuable resource for future genetic studies of human
      diseases, population genetics and evolution in this population.

PMID- 27049302
TI  - 'You should at least ask'. The expectations, hopes and fears of rare disease
      patients on large-scale data and biomaterial sharing for genomics research.
AB  - Within the myriad articles about participants' opinions of genomics research, the
      views of a distinct group - people with a rare disease (RD) - are unknown. It is
      important to understand if their opinions differ from the general public by dint
      of having a rare disease and vulnerabilities inherent in this. Here we document
      RD patients' attitudes to participation in genomics research, particularly around
      large-scale, international data and biosample sharing. This work is unique in
      exploring the views of people with a range of rare disorders from many different
      countries. The authors work within an international, multidisciplinary
      consortium, RD-Connect, which has developed an integrated platform connecting
      databases, registries, biobanks and clinical bioinformatics for RD research.
      Focus groups were conducted with 52 RD patients from 16 countries. Using a
      scenario-based approach, participants were encouraged to raise topics relevant to
      their own experiences, rather than these being determined by the researcher.
      Issues include wide data sharing, and consent for new uses of historic samples
      and for children. Focus group members are positively disposed towards research
      and towards allowing data and biosamples to be shared internationally.
      Expressions of trust and attitudes to risk are often affected by the nature of
      the RD which they have experience of, as well as regulatory and cultural
      practices in their home country. Participants are concerned about data security
      and misuse. There is an acute recognition of the vulnerability inherent in having
      a RD and the possibility that open knowledge of this could lead to
      discrimination.

PMID- 27049304
TI  - A novel kinase mutation in VEGFR-1 predisposes its alphaC-helix/activation loop
      towards allosteric activation: Atomic insights from protein simulation.
AB  - Vascular endothelial growth factor receptor 1 (VEGFR-1) has been implicated in
      diverse pathologies, including cancers. Although VEGFR-1 is considered as
      functionally impaired kinase, its decoy characteristics make it an important
      regulator of VEGFR-mediated signaling, particularly in tumor angiogenesis. VEGFR
      1 conveys signaling via its tyrosine kinase (TK) domain whose activation is
      regulated by phosphorylation of specific tyrosine residues. Thus dysregulation of
      VEGFR-1 signaling, as reported in most of the cancers, might be a consequence of
      altered phosphorylation that could be attributed to genotypic variations in its
      TK domain. Considering the importance of TK domain of VEGFR-1, we carried out its
      mutational screening in 84 clinically validated and histopathologically confirmed
      colorectal cancer patients. By means of direct DNA sequencing and SNP analyses,
      eight novel variations, including one synonymous, two deletion, one missense and
      four intronic variations, were reported in the TK domain of VEGFR-1.
      rs730882263:C>G variation specifically reported in colon cancer, representing a
      single-atomic change (Sulfur to Oxygen) in the predicted (p.Cys1110Ser) protein,
      was observed as potentially deleterious variation as assessed by multiple single
      nucleotide polymorphism prediction servers. Molecular dynamics simulations of
      VEGFR-1 Wt and (p.Cys1110Ser) variant models revealed major conformational
      changes in variant protein presumptuously generating an open conformation thereby
      exposing the activation domain and consequently increasing the probability of
      phosphorylation events: a condition frequently reported in cancers.

PMID- 27049303
TI  - Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal
      dysplasia including oligodontia in Palestinian families.
AB  - Tooth development is controlled by the same processes that regulate formation of
      other ectodermal structures. Mutations in the genes underlying these processes
      may cause ectodermal dysplasia, including severe absence of primary or permanent
      teeth. Four consanguineous Palestinian families presented with oligodontia and
      hair and skin features of ectodermal dysplasia. Appearance of ectodermal
      dysplasia was consistent with autosomal recessive inheritance. Exome sequencing
      followed by genotyping of 56 informative relatives in the 4 families suggests
      that the phenotype is due to homozygosity for KREMEN1 p.F209S (c.626 T>C) on
      chromosome 22 at g.29,521,399 (hg19). The variant occurs in the highly conserved
      extracellular WSC domain of KREMEN1, which is known to be a high affinity
      receptor of Dickkopf-1, a component of the Dickkopf-Kremen-LRP6 complex, and a
      potent regulator of Wnt signaling. The Wnt signaling pathway is critical to
      development of ectodermal structures. Mutations in WNT10A, LRP6, EDA, and other
      genes in this pathway lead to tooth agenesis with or without other ectodermal
      anomalies. Our results implicate KREMEN1 for the first time in a human disorder
      and provide additional details on the role of the Wnt signaling in ectodermal and
      dental development.

PMID- 27049305
TI  - Clinical utility gene card for: Peters plus syndrome.

PMID- 27049306
TI  - IL-1beta and IL-18 inhibition of HIV-1 replication in Jurkat cells and PBMCs.
AB  - HIV-1 infection-induced apoptosis is able to ensure viral replication. The death
      of some CD4+ T cells residing in lymphoid tissues can be induced by HIV-1
      infection through caspase-1 driven pyroptosis with release of cytokine of IL
      1beta and IL-18. It is not well known whether IL-1beta and IL-18 affect HIV-1
      replication in lymphocytic cells. Using susceptible lymphocytic cell line, Jurkat
      cells, and primary peripheral blood mononuclear cells (PBMCs), we studied the
      effects of IL-1beta and IL-18 on HIV-1 replication. We found that treatment with
      exogenous IL-1beta protein (rIL-1beta) and IL-18 protein (rIL-18), or expression
      of IL-1beta and IL-18 significantly reduced HIV-1 replication. HIV-1 infection
      enhanced caspase-3 expression and its activation, and had no effects on caspase-1
      activity. Treatment with rIL-1beta and rIL-18 dramatically lowered caspase-3
      activity. IL-1beta and IL-18 also played roles in diminishing reactivation of
      viral replication from latency in J1.1 cells. These results indicate that IL
      1beta and IL-18 are able to inhibit HIV-1 replication, and their effects may be
      due to signaling through apoptosis involved in inactivation of caspase-3
      activity.

PMID- 27049307
TI  - Overexpression of Dyrk1A regulates cardiac troponin T splicing in cells and mice.
AB  - The human heart expresses four isoforms of cardiac troponin T (cTnT) through
      alternative splicing of exons 4 and 5 of the cTnT gene. Alternative splicing of
      cTnT exon 5 is developmentally regulated. cTnT isoforms containing exon 5 are
      expressed in the fetal and neonatal heart but not in the mature heart. SRp55 is
      an essential splicing factor involved in cTnT exon 5 splicing and it is
      phosphorylated by Dyrk1A (dual specificity tyrosine phosphorylation regulated
      kinase 1A). In the present study, we found Dyrk1A interacted with SRp55 and
      enhanced its promotion of cTnT exon 5 inclusion. The shift from cTnT exon 5
      inclusion to exclusion during development was delayed in the heart of Ts65Dn mice
      due to Dyrk1A overexpression. These results provide new insight into the role of
      Dyrk1A in the neonatal cardiac development.

PMID- 27049308
TI  - Hydroxychloroquine binding to cytoplasmic domain of Band 3 in human erythrocytes:
      Novel mechanistic insights into drug structure, efficacy and toxicity.
AB  - Hydroxychloroquine (HCQ) is a widely used drug in the treatment of autoimmune
      diseases, such as arthritis and systemic lupus erythematosus. It has also been
      prescribed for the treatment of malaria owing to its lower toxicity compared to
      its closely related compound chloroquine (CQ). However, the mechanisms of action
      of HCQ in erythrocytes (which bind preferentially this drug) have not been
      documented and the reasons underlying the lower side effects of HCQ compared to
      CQ remain unclear. Here we show that, although the activity of erythrocyte
      lactate dehydrogenase (LDH), but not GAPDH, was inhibited by both HCQ and CQ in
      vitro, LDH activity in erythrocytes incubated with 20 mM HCQ was not
      significantly reduced within 5 h in contrast to CQ did. Using HCQ coupled
      Sepharose chromatography (HCQ-Sepharose), we identified Band 3, spectrin,
      ankyrin, protein 4.1R and protein 4.2 as HCQ binding proteins in human
      erythrocyte plasma membrane. Recombinant cytoplasmic N-terminal 43 kDa domain of
      Band 3 bound to HCQ-Sepharose and was eluted with 40 mM (but not 20 mM) HCQ. Band
      3 transport activity was reduced by only 23% in the presence of 20 mM HCQ. Taken
      together, these data demonstrate that HCQ binds to the cytoplasmic N-terminal
      domain of Band 3 in human erythrocytes but does not inhibit dramatically its
      transport activity. We hypothesize that the trapping of HCQ on Band 3 contributes
      to the lower side effects of the drug on energy production in erythrocytes.

PMID- 27049309
TI  - Emamectin is a non-selective allosteric activator of nicotinic acetylcholine
      receptors and GABAA/C receptors.
AB  - Avermectins are a group of compounds isolated from a soil-dwelling bacterium.
      They have been widely used as parasiticides and insecticides, acting by
      relatively irreversible activation of invertebrate chloride channels. Emamectin
      is a soluble derivative of an avermectin. It is an insecticide, which
      persistently activates glutamate-gated chloride channels. However, its effects on
      mammalian ligand-gated ion channels are unknown. To this end, we tested the
      effect of emamectin on two cation selective nicotinic receptors and two GABA
      gated chloride channels expressed in Xenopus oocytes using two-electrode voltage
      clamp. Our results demonstrate that emamectin could directly activate alpha7
      nAChR, alpha4beta2 nAChR, alpha1beta2gamma2 GABAA receptor and rho1 GABAC
      receptor concentration dependently, with similar potencies for each channel.
      However, the potencies for it to activate these channels were at least two orders
      of magnitude lower than its potency of activating invertebrate glutamate-gated
      chloride channel. In contrast, ivermectin only activated the alpha1beta2gamma2
      GABAA receptor.

PMID- 27049310
TI  - MicroRNA-376c suppresses non-small-cell lung cancer cell growth and invasion by
      targeting LRH-1-mediated Wnt signaling pathway.
AB  - MicroRNAs (miRNAs) that negatively regulate gene expression have emerged as novel
      therapeutic tools for cancer treatment. In this study, we investigated the
      potential role of Liver receptor homolog-1 (LRH-1), a novel oncogene, in non
      small-cell lung cancer (NSCLC), and examined the regulation of LRH-1 by miRNAs.
      We found that LRH-1 was highly overexpressed in NSCLC cell lines. Knockdown of
      LRH-1 by small interfering RNA significantly inhibited NSCLC cell growth and
      invasion. miR-376c directly targeted the 3'-untranslated region (UTR) of LRH-1
      and negatively regulated LRH-1 expression, as detected by dual-luciferase
      reporter assay, real-time quantitative polymerase chain reaction and Western blot
      analysis. Further data showed that miR-376c expression was inversely correlated
      with LRH-1 expression in clinical cancer samples. Overexpression of miR-376c
      could inhibit NSCLC cell growth and invasion as well as Wnt signaling. In
      contrast, depletion of miR-376c exhibited the opposite effects. Moreover, these
      effects of miR-376c overexpression were partially abrogated by overexpression of
      LRH-1. Taken together, these results indicate that LRH-1 is involved in
      regulating the growth and invasion of NSCLC cells and that miR-376c inhibits
      NSCLC cell growth and invasion by targeting LRH-1, providing a novel insight into
      the potential for development of anti-cancer drugs for NSCLC.

PMID- 27049311
TI  - miR-613 inhibits the growth and invasiveness of human hepatocellular carcinoma
      via targeting DCLK1.
AB  - microRNAs (miRNAs) play key regulatory roles in various biological processes. In
      this study, we aimed to determine the expression and biological roles of miR-613
      in hepatocellular carcinoma (HCC). Compared with non-cancerous liver tissues, miR
      613 was significantly downregulated in HCC tissues. Ectopic expression of miR-613
      significantly suppressed the proliferation and invasion of Hep3B and SMMC-7721
      HCC cells. Bioinformatic and luciferase reporter analysis identified doublecortin
      like kinase 1 (DCLK1) as a direct target of miR-613. Overexpression of miR-613
      inhibited the expression of DCLK1 in HCC cells. There was a significant inverse
      correlation between miR-613 and DCLK1 protein expression in HCC samples. Small
      interfering RNA-mediated silencing of DCLK1 phenocopied the suppressive effects
      of miR-613 in HCC cells. Rescue experiments demonstrated that co-transfection of
      DCLK1 lacking the 3'-untranslated region partially prevented miR-613-induced
      suppression of HCC cell proliferation and invasion. In vivo studies confirmed
      that miR-613 overexpression retarded the growth of Hep3B xenograft tumors in nude
      mice, coupled with a reduction in the percentage of Ki67-positive tumor cells and
      DCLK1 protein expression. In conclusion, we provide first evidence for the
      suppressive activity of miR-613 in HCC, which is causally linked to targeting of
      DCLK1. Restoration of miR-613 may provide a potential therapeutic strategy for
      HCC.

PMID- 27049312
TI  - Vagal nerve stimulation attenuates IL-6 and TNFalpha expression in respiratory
      regions of the developing rat brainstem.
AB  - Pre-term infants are at greater risk for systemic infection due to an
      underdeveloped immune system. Airway infection results in immune up-regulation of
      early pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL
      6) and tumor necrosis factor-alpha (TNFalpha) in the brainstem. Current treatment
      for neonatal infection involves antibiotic administration. We previously showed
      that LPS injected into the trachea of neonatal rats causes changes in breathing
      and in IL-1beta expression in the nucleus tractus solitarii (NTS) and hypoglossal
      motor nucleus (XII). We hypothesize that lipopolysaccharide (LPS) instilled in
      the trachea also causes the up-regulation of IL-6 and TNFalpha in the brainstem
      autonomic control regions. To test this hypothesis we injected LPS into the
      trachea of rat pups (postnatal ages 10-12days) and then assessed changes in IL-6
      and TNFalpha. Vagal nerve stimulation has been used in the treatment of many
      inflammatory disorders, including sepsis. Our experiments show that VNS
      attenuates the upregulation of IL-6 and TNFalpha caused by LPS and may be a
      viable alternative to antibiotics.

PMID- 27049313
TI  - Articles on health policies and health services in Cadernos de Saude
      Publica/Reports in Public Health.

PMID- 27049314
TI  - [Impact of PCV10 pneumococcal vaccine on mortality from pneumonia in children
      less than one year of age in Santa Catarina State, Brazil].
AB  - The aim of this study was to evaluate the impact of PCV10 pneumococcal vaccine on
      mortality from pneumonia in children less than one year of age in Santa Catarina
      State, Brazil, comparing the four years prior and the four years subsequent to
      the vaccine's introduction in 2010. This ecological study used data from the
      Mortality Information System and vaccination coverage of children less than one
      year. Data were grouped by municipalities of residence and regions. Average
      mortality from pneumonia in children under one year decreased from 29.69 to 23.40
      per 100,000, comparing 2006-2009 and 2010-2013, or a reduction of 11%. However
      there were differences between regions with a drop in mortality (Grande
      Florianopolis, Sul, Planalto Norte, and Nordeste) and others with an increase in
      the annual rates (Oeste, Itajai, and Serra). In short, the state as a whole
      showed 11% reduction in mortality from pneumonia in children less than one year
      of age, four years after implementing routine PCV10 vaccination in the National
      Immunization Program, but with heterogeneous effects when comparing regions of
      the state. 

PMID- 27049315
TI  - [Nutritional challenges in the Brazilian Unified National Health System for
      building the interface between health and food and nutritional security].
AB  - This article discusses the establishment of inter-sector action between health
      and food and nutritional security in Brazil from 2003 to 2010, when this issue
      was launched as a priority on the government's agenda. A qualitative study was
      developed according to constructivist epistemology, using key-informant
      interviews in the field's nationwide social oversight body. Advances and
      challenges in this process are addressed as analytical categories. The National
      Food and Nutrition Policy (PNAN) was mentioned as the link between the two
      fields, decentralized through a network with activity in the states and
      municipalities. However, the study found political, institutional, and
      operational obstacles to the effective implementation of the PNAN in the
      Brazilian Unified National Health System and consequently to a contribution to
      the advancement of Health and Food and Nutritional Security in the country. The
      predominance of the biomedical, curative, and high-complexity model was cited as
      the principal impediment, while health promotion policies like the PNAN were
      assigned secondary priority. 

PMID- 27049316
TI  - [Political dimensions of an epidemic: the case of influenza A (H1N1) in the
      Argentine press].
AB  - The current study addresses social representations of the influenza A (H1N1)
      epidemic in Argentina in 2009, in the country's mainstream newspapers. The
      methodology was twofold, qualitative and quantitative, with an analysis of two
      dimensions: the construction of the epidemic as an "object" (designation and
      characterization) and the sources of information in the news stories, seeking to
      identify the social actors involved in each case. The results show that
      designating the epidemic as "H1N1" rather than "swine flu" was a conscious
      political decision to exempt a hazardous form of livestock production from its
      role in the disease, while focusing responsibility on individual patients. The
      study addresses the relations between recommendations by policy spokespersons
      (especially at the international level), the pharmaceuticalization of the
      epidemic, shifting of the population's demands to validate biomedical hegemony,
      and local press coverage of the epidemic. 

PMID- 27049318
TI  - The Influence of Perioperative Dexmedetomidine on Patients Undergoing Cardiac
      Surgery: A Meta-Analysis.
AB  - BACKGROUND: The use of dexmedetomidine may have benefits on the clinical outcomes
      of cardiac surgery. We conducted a meta-analysis comparing the postoperative
      complications in patients undergoing cardiac surgery with dexmedetomidine versus
      other perioperative medications to determine the influence of perioperative
      dexmedetomidine on cardiac surgery patients. METHODS: Randomized or quasi
      randomized controlled trials comparing outcomes in patients who underwent cardiac
      surgery with dexmedetomidine, another medication, or a placebo were retrieved
      from EMBASE, PubMed, the Cochrane Library, and Science Citation Index. RESULTS: A
      total of 1702 patients in 14 studies met the selection criteria among 1,535
      studies that fit the research strategy. Compared to other medications,
      dexmedetomidine has combined risk ratios of 0.28 (95% confidence interval [CI]
      0.15, 0.55, P = 0.0002) for ventricular tachycardia, 0.35 (95% CI 0.20, 0.62, P =
      0.0004) for postoperative delirium, 0.76 (95% CI 0.55, 1.06, P = 0.11) for atrial
      fibrillation, 1.08 (95% CI 0.74, 1.57, P = 0.69) for hypotension, and 2.23 (95%
      CI 1.36, 3.67, P = 0.001) for bradycardia. In addition, dexmedetomidine may
      reduce the length of intensive care unit (ICU) and hospital stay. CONCLUSIONS:
      This meta-analysis revealed that the perioperative use of dexmedetomidine in
      patients undergoing cardiac surgery can reduce the risk of postoperative
      ventricular tachycardia and delirium, but may increase the risk of bradycardia.
      The estimates showed a decreased risk of atrial fibrillation, shorter length of
      ICU stay and hospitalization, and increased risk of hypotension with
      dexmedetomidine.

PMID- 27049319
TI  - Age, Growth and Spatial Distribution of the Life Stages of the Shortfin Mako,
      Isurus oxyrinchus (Rafinesque, 1810) Caught in the Western and Central Atlantic.
AB  - The shortfin mako (Isurus oxyrinchus) is a highly migratory pelagic shark that
      preferentially inhabits oceanic regions in practically all oceans. The wide
      distribution range of this species renders it susceptible to coastal and oceanic
      fishing operations. The International Union for Conservation of Nature (IUCN) and
      the International Commission for the Conservation of Atlantic Tunas (ICCAT)
      consider this species to be highly vulnerable, especially due to its biological
      parameters, which are different from those of other sharks that occupy the same
      niche (e.g., Prionace glauca). Consequently, considerable declines in abundance
      have been detected over various parts of its range, most of which are linked to
      oceanic longline fishing. The species has conflicting life history parameters in
      studies conducted in the last 30 years, especially with regard to age and growth.
      The main discrepancies regard the interpretation of the periodicity of the
      deposition of band pairs (BPs) on vertebrae and the possibility of ontogenetic
      variations in growth. Shortfin mako sharks (n = 1325) were sampled by onboard
      observers of the Brazilian chartered pelagic longline fleet based in northeast
      Brazil from 2005 to 2011. Lengths were 79 to 250 and 73 to 296 cm (fork length,
      FL) for males and females, respectively, with a statistically significant
      difference in size between sexes and differences in the proportion of individuals
      in each size class. The onboard observers collected a subsample of vertebrae (n =
      467), only 234 of which were suitable for analyses. Reliability between readings
      was satisfactory. However, it was not possible to validate periodicity in the
      formation of age bands in the sample. Thus, the von Bertalanffy growth function
      was used to calculate growth rates for the species through the interpretation of
      BPs in different scenarios: one BP per year (s1), two BPs per year (s2) and two
      BPs per year until five years of life (s3). Growth parameters varied for both
      females (Linf = 309.7[s3] to 441.6[s1]; k = 0.04[s1] to 0.13[s3]; t0 = -7.08[s1]
      and -3.27[s3]) and males (Linf = 291.5[s3] to 340.2[s1]; k = 0.04[s1] to
      0.13[s3]; t0 = -7.08[s1] and -3.27[s3]). To advance the understanding of the use
      of habitat, the first analysis of the spatial distribution of the life stages of
      the shortfin mako sharks caught by commercial longline fishing operations in the
      South Atlantic was performed. The findings indicate that the portion of the
      population exploited by the fleets is predominantly juvenile and future actions
      should take the following issues into account: improvements in the efficiency of
      data collection procedures, the reestablishment of the onboard observer program,
      emergency investments in studies that can contribute to a better understanding of
      habitat use and life history theory. 

PMID- 27049320
TI  - Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in
      the Central Nervous System of Rats.
AB  - Xylazine is a potent analgesic extensively used in veterinary and animal
      experimentation. Evidence exists that the analgesic effect can be inhibited using
      adenosine 5'-monophosphate activated protein kinase (AMPK) inhibitors.
      Considering this idea, the aim of this study was to investigate whether the AMPK
      signaling pathway is involved in the central analgesic mechanism of xylazine in
      the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley
      rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus
      and brainstem were collected for determination of liver kinase B1 (LKB1) and
      AMPKalpha mRNA expression using quantitative real-time polymerase chain reaction
      (qPCR), and phosphorylated LKB1 and AMPKalpha levels using western blot. The
      results of our study showed that compared with the control group, xylazine
      induced significant increases in AMPK activity in the cerebral cortex,
      hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01).
      Increased AMPK activities were accompanied with increased phosphorylation levels
      of LKB1 in corresponding regions of rats. The protein levels of phosphorylated
      LKB1 and AMPKalpha in these regions returned or tended to return to control group
      levels. However, in the brainstem, phosphorylated LKB1 and AMPKalpha protein
      levels were decreased by xylazine compared with the control (P < 0.05). In
      conclusion, our data indicates that xylazine alters the activities of LKB1 and
      AMPK in the central nervous system of rats, which suggests that xylazine affects
      the regulatory signaling pathway of the analgesic mechanism in the rat brain. 

PMID- 27049321
TI  - The 'Brain Shadowing Sign': A Novel Marker of Fetal Craniosynostosis.
AB  - INTRODUCTION: The prenatal diagnosis of fetal craniosynostosis is challenging,
      especially in single-suture cases. When sutures are obliterated, sound waves fail
      to penetrate the cortical bone, creating an evident acoustic shadow on the
      underlying brain. The objective of this study was to evaluate the yield of the
      'brain shadowing sign' (BSS) as a novel sonographic marker for craniosynostosis.
      SUBJECTS AND METHODS: Patients with an antenatal diagnosis of fetal
      craniosynostosis (cases) and healthy controls paired for gestational age were
      enrolled in this retrospective case-control study. Two-dimensional scans were
      assessed by three examiners for the presence of the BSS and additional fetal
      findings. RESULTS: The BSS was clearly depicted in all 24 cases on the first
      analysis and in 22 cases on the second analysis. No fetus from the control group
      (n = 48) presented the BSS in any of the analyses. Fifteen cases had isolated
      craniosynostosis and 9 were syndromic (Apert, Saethre-Chotzen and
      craniofrontonasal syndromes), which were diagnosed significantly earlier due to
      additional malformations. DISCUSSION: The BSS is a novel sonographic marker of
      craniosynostosis which can be used to increase the diagnostic rate of this rare
      condition and does not require the use of high-definition three-dimensional
      transducers to be depicted.

PMID- 27049322
TI  - Predicting and Evaluating the Epidemic Trend of Ebola Virus Disease in the 2014
      2015 Outbreak and the Effects of Intervention Measures.
AB  - We constructed dynamic Ebola virus disease (EVD) transmission models to predict
      epidemic trends and evaluate intervention measure efficacy following the 2014 EVD
      epidemic in West Africa. We estimated the effective vaccination rate for the
      population, with basic reproduction number (R0) as the intermediate variable.
      Periodic EVD fluctuation was analyzed by solving a Jacobian matrix of
      differential equations based on a SIR (susceptible, infective, and removed)
      model. A comprehensive compartment model was constructed to fit and predict EVD
      transmission patterns, and to evaluate the effects of control and prevention
      measures. Effective EVD vaccination rates were estimated to be 42% (31-50%), 45%
      (42-48%), and 51% (44-56%) among susceptible individuals in Guinea, Liberia and
      Sierra Leone, respectively. In the absence of control measures, there would be
      rapid mortality in these three countries, and an EVD epidemic would be likely
      recur in 2035, and then again 8~9 years later. Oscillation intervals would
      shorten and outbreak severity would decrease until the periodicity reached ~5.3
      years. Measures that reduced the spread of EVD included: early diagnosis,
      treatment in isolation, isolating/monitoring close contacts, timely corpse
      removal, post-recovery condom use, and preventing or quarantining imported cases.
      EVD may re-emerge within two decades without control and prevention measures.
      Mass vaccination campaigns and control and prevention measures should be
      instituted to prevent future EVD epidemics. 

PMID- 27049323
TI  - A Prospective Randomized Controlled Study to Compare Acupuncture and Dapoxetine
      for the Treatment of Premature Ejaculation.
AB  - PURPOSE: To compare the safety and efficacy of dapoxetine and acupuncture for the
      treatment of premature ejaculation (PE) with other treatment methods. METHODS:
      One hundred twenty patients with PE in an outpatient urology clinic were
      randomized to receive dapoxetine 30 mg and 60 mg, acupuncture or sham
      acupuncture. The intravaginal ejaculatory latency time (IELT), the PE diagnostic
      tool (PEDT) score, and adverse events were compared. RESULTS: There were no
      differences between the groups in terms of age, body mass index, baseline IELT
      and PEDT scores (p > 0.05). After 4 weeks, IELT was significantly longer compared
      to baseline values in all groups (p < 0.001 for all comparisons). Comparisons
      between the groups showed that changes in IELT and PEDT observed after 4 weeks
      with dapoxetine 60 mg was significantly higher than those achieved in all other
      groups (p < 0.001 for all comparisons), changes observed with dapoxetine 30 mg
      was significantly higher than those achieved with acupuncture and sham
      acupuncture groups (p < 0.001 for both comparisons) and changes observed with
      acupuncture was significantly higher than those observed with sham acupuncture (p
      < 0.001). CONCLUSION: Our results confirm previous reports on the efficacy and
      safety of dapoxetine. Although less effective than dapoxetine, acupuncture had a
      significant ejaculation-delaying effect.

PMID- 27049324
TI  - Re-Occupancy of Breeding Territories by Ferruginous Hawks in Wyoming:
      Relationships to Environmental and Anthropogenic Factors.
AB  - Grassland and shrubland birds are declining globally due in part to anthropogenic
      habitat modification. Because population performance of these species is also
      influenced by non-anthropogenic factors, it is important to incorporate all
      relevant ecological drivers into demographic models. We used design-based
      sampling and occupancy models to test relationships of environmental factors that
      influence raptor demographics with re-occupancy of breeding territories by
      ferruginous hawks (Buteo regalis) across Wyoming, USA, 2011-2013. We also tested
      correlations of territory re-occupancy with oil and gas infrastructure-a leading
      cause of habitat modification throughout the range of this species of
      conservation concern. Probability of re-occupancy was not related to any
      covariates we investigated in 2011, had a strong negative relationship with cover
      of sagebrush (Artemisia spp.) in 2012, was slightly higher for territories with
      artificial platforms than other nest substrates in 2013, and had a positive
      relationship with abundance of ground squirrels (Urocitellus spp.) that was
      strong in 2012 and weak in 2013. Associations with roads were weak and varied by
      year, road-type, and scale: in 2012, re-occupancy probability had a weak positive
      correlation with density of roads not associated with oil and gas fields at the
      territory-scale; however, in 2013 re-occupancy had a very weak negative
      correlation with density of oil and gas field roads near nest sites (<=500 m).
      Although our results indicate re-occupancy of breeding territories by ferruginous
      hawks was compatible with densities of anthropogenic infrastructure in our study
      area, the lack of relationships between oil and gas well density and territory re
      occupancy may have occurred because pre-treatment data were unavailable. We used
      probabilistic sampling at a broad spatial extent, methods to account for
      imperfect detection, and conducted extensive prey sampling; nonetheless, future
      research using before-after-control-impact designs is needed to fully assess
      impacts of oil and gas development on ferruginous hawks. 

PMID- 27049326
TI  - Influence of Manatees' Diving on Their Risk of Collision with Watercraft.
AB  - Watercraft pose a threat to endangered Florida manatees (Trichechus manatus
      latirostris). Mortality from watercraft collisions has adversely impacted the
      manatee population's growth rate, therefore reducing this threat is an important
      management goal. To assess factors that contribute to the risk of watercraft
      strikes to manatees, we studied the diving behavior of nine manatees carrying GPS
      tags and time-depth recorders in Tampa Bay, Florida, during winters 2002-2006. We
      applied a Bayesian formulation of generalized linear mixed models to depth data
      to model the probability (Pt) that manatees would be no deeper than 1.25 m from
      the water's surface as a function of behavioral and habitat covariates. Manatees
      above this threshold were considered to be within striking depth of a watercraft.
      Seventy-eight percent of depth records (individual range 62-86%) were within
      striking depth (mean = 1.09 m, max = 16.20 m), illustrating how vulnerable
      manatees are to strikes. In some circumstances manatees made consecutive dives to
      the bottom while traveling, even in areas >14 m, possibly to conserve energy.
      This is the first documentation of potential cost-efficient diving behavior in
      manatees. Manatees were at higher risk of being within striking depth in shallow
      water (<0.91 m), over seagrass, at night, and while stationary or moving slowly;
      they were less likely to be within striking depth when <=50 m from a charted
      waterway. In shallow water the probability of a manatee being within striking
      depth was 0.96 (CI = 0.93-0.98) and decreased as water depth increased. The
      probability was greater over seagrass (Pt = 0.96, CI = 0.93-0.98) than over other
      substrates (Pt = 0.73, CI = 0.58-0.84). Quantitative approaches to assessing risk
      can improve the effectiveness of manatee conservation measures by helping
      identify areas for protection. 

PMID- 27049325
TI  - Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate
      Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY
      Study.
AB  - BACKGROUND: Metabolic abnormalities that lead to type 2 diabetes mellitus begin
      in early childhood. OBJECTIVES: We investigate whether common genetic variants
      identified in adults have an effect on glucose in early life. METHODS: 610
      newborns, 463 mothers, and 366 fathers were included in the present study. Plasma
      glucose and anthropometric characteristics were collected at birth, 3, and 5
      years. After quality assessment, 37 SNPs, which have demonstrated an association
      with fasting plasma glucose at the genome-wide threshold in adults, were studied.
      Quantitative trait disequilibrium tests and mixed-effects regressions were
      conducted to estimate an effect of the SNPs on glucose. RESULTS: Risk alleles for
      6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A,
      CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10-3 <= P <= 4.60x10-2). Together,
      these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype
      score (P = 6.33x10-5). None of the associations described in the present study
      have been reported previously in early childhood. CONCLUSION: Our data support
      the notion that a subset of loci contributing to plasma glucose variation in
      adults has an effect at birth and in early life.

PMID- 27049327
TI  - Hierarchical Polymer Brushes with Dominant Antibacterial Mechanisms Switching
      from Bactericidal to Bacteria Repellent.
AB  - Although polycationic surfaces have high antimicrobial efficacies, they suffer
      from high toxicity to mammalian cells and severe surface accumulation of dead
      bacteria. For the first time, we propose a surface-initiated photoiniferter
      mediated polymerization (SI-PIMP) strategy of constructing a "cleaning"
      zwitterionic outer layer on a polycationic bactericidal background layer to
      physically hinder the availability of polycationic moieties for mammalian cells
      in aqueous service. In dry conditions, the polycationic layer exerts the contact
      active bactericidal property toward the adherent bacteria, as the zwitterionic
      layer collapses. In aqueous environment, the zwitterionic layer forms a hydration
      layer to significantly inhibit the attachment of planktonic bacteria and the
      accumulation of dead bacteria, while the polycationic layer kills bacteria
      occasionally deposited on the surface, thus preserving the antibacterial
      capability for a long period. More importantly, the zwitterionic hydrated layer
      protects the mammalian cells from toxicity induced by the bactericidal background
      layer, and therefore hierarchical antibacterial surfaces present much better
      biocompatibility than that of the naked cationic references. The dominant
      antibacterial mechanism of the hierarchical surfaces can switch from the
      bactericidal efficacy in dry storage to the bacteria repellent capability in
      aqueous service, showing great advantages in the infection-resistant
      applications.

PMID- 27049328
TI  - Correction to HER2 Targeted Breast Cancer Therapy with Switchable "Off/On"
      Multifunctional "Smart" Magnetic Polymer Core-Shell Nanocomposites.

PMID- 27049329
TI  - Reply to: Could this be the pioneering case of short-blanket syndrome? Filippou
      et al.

PMID- 27049330
TI  - Mycophenolate mofetil is an effective and safe option for the management of
      systemic sclerosis-associated interstitial lung disease: results from the
      Australian Scleroderma Cohort Study.
AB  - OBJECTIVES: To report the efficacy and tolerability of mycophenolate mofetil
      (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated
      interstitial lung disease (SSc-ILD). METHODS: Patients in the Australian
      Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD
      confirmed on high resolution computed tomography (HRCT) chest were identified and
      their pulmonary function tests (PFTs) retrieved. Individuals with available
      results for T-1 (12 months prior to treatment commencement), T0 (date of
      treatment commencement) and at least one subsequent time point were included in
      the drug efficacy analysis. The Wilcoxon signed-rank test was used to compare
      absolute FVC at T1, T0, 12 months (T1), 24 months (T2) and 36 months (T3).
      Analysis of drug tolerability included all identified patients treated with MMF
      or AZA. RESULTS: 18/22 patients treated with MMF and 29/49 treated with AZA had
      adequate PFTs for inclusion in the drug efficacy analysis. Median absolute FVC at
      T1 for MMF treatment was 2.50L, declining to 2.12L at T0 (p=0.02). Following MMF
      therapy, FVC results were stable at T1 (2.13L, p=0.86), T2 (2.17L, p=0.65) and T3
      (2.25L, p=0.78). In the AZA group, a statistically significant decline did not
      occur prior to treatment, however FVC results remained stable at T1, T2 and
      T3.Adverse events leading to early discontinuation (<12 months treatment) were
      less common in the MMF group (4/22 vs. 13/49). Gastrointestinal complications
      were the main cause of discontinuation in both groups. CONCLUSIONS: In patients
      with SSc-ILD with declining pulmonary function, MMF therapy was associated with
      stability for up to 36 months. Early adverse events leading to discontinuation
      occurred less frequently in patients treated with MMF than in AZA treated
      patients.

PMID- 27049332
TI  - Total Synthesis of (-)-L-755,807: Establishment of Relative and Absolute
      Configurations.
AB  - The first total synthesis of (-)-L-755,807 and its three stereoisomers was
      achieved by our Horner-Wadsworth-Emmons reaction for stereoselective formation of
      trisubstituted olefins, highly diastereoselective Darzens condensation to
      construct the epoxy-gamma-lactam ring, and late-stage coupling of the ring and
      side-chain segments for efficient convergent synthesis. This synthesis shows that
      the originally proposed structure of natural (-)-L-755,807 was incorrect and
      establishes its relative and absolute configurations. 

PMID- 27049331
TI  - Preoperative blood transfusions for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease is one of the commonest severe monogenic
      disorders in the world, due to the inheritance of two abnormal haemoglobin (beta
      globin) genes. Sickle cell disease can cause severe pain, significant end-organ
      damage, pulmonary complications, and premature death. Surgical interventions are
      more common in people with sickle cell disease, and occur at much younger ages
      than in the general population. Blood transfusions are frequently used prior to
      surgery and several regimens are used but there is no consensus over the best
      method or the necessity of transfusion in specific surgical cases. This is an
      update of a Cochrane review first published in 2001. OBJECTIVES: To determine
      whether there is evidence that preoperative blood transfusion in people with
      sickle cell disease undergoing elective or emergency surgery reduces mortality
      and perioperative or sickle cell-related serious adverse events.To compare the
      effectiveness of different transfusion regimens (aggressive or conservative) if
      preoperative transfusions are indicated in people with sickle cell disease.
      SEARCH METHODS: We searched for relevant trials in The Cochrane Library, MEDLINE
      (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980),
      and ongoing trial databases; all searches current to 23 March 2016.We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 18
      January 2016. SELECTION CRITERIA: All randomised controlled trials and quasi
      randomised controlled trials comparing preoperative blood transfusion regimens to
      different regimens or no transfusion in people with sickle cell disease
      undergoing elective or emergency surgery. There was no restriction by outcomes
      examined, language or publication status. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial eligibility and the risk of bias and
      extracted data. MAIN RESULTS: Three trials with 990 participants were eligible
      for inclusion in the review. There were no ongoing trials identified. These
      trials were conducted between 1988 and 2011. The majority of people included had
      haemoglobin (Hb) SS SCD. The majority of surgical procedures were considered low
      or intermediate risk for developing sickle cell-related complications. Aggressive
      versus simple red blood cell transfusions One trial (551 participants) compared
      an aggressive transfusion regimen (decreasing sickle haemoglobin to less than
      30%) to a simple transfusion regimen (increasing haemoglobin to 100 g/l). This
      trial re-randomised participants and therefore quantitative analysis was only
      possible on two subsets of data: participants undergoing cholecystectomy (230
      participants); and participants undergoing tonsillectomy or adenoidectomy
      surgeries (107 participants). Data were not combined as we do not know if any
      participant received both surgeries. Overall, the quality of the evidence was
      very low across different outcomes according to GRADE methodology. This was due
      to the trial being at high risk of bias primarily due to lack of blinding,
      indirectness and the outcome estimates being imprecise. Cholecystectomy subgroup
      results are reported in the abstract. Results for both subgroups were
      similar.There was no difference in all-cause mortality between people receiving
      aggressive transfusions and those receiving conservative transfusions. No deaths
      occurred in either subgroup.There were no differences between the aggressive
      transfusion group and conservative transfusion group in the number of people
      developing:* an acute chest syndrome, risk ratio 0.84 (95% confidence interval
      0.38 to 1.84) (one trial, 230 participants, very low quality evidence);* vaso
      occlusive crisis, risk ratio 0.30 (95% confidence interval 0.09 to 1.04) (one
      trial, 230 participants, very low quality evidence);* serious infection, risk
      ratio 1.75 (95% confidence interval 0.59 to 5.18) (one trial, 230 participants,
      very low quality evidence);* any perioperative complications, risk ratio 0.75
      (95% confidence interval 0.36 to 1.55) (one trial, 230 participants, very low
      quality evidence);* a transfusion-related complication, risk ratio 1.85 (95%
      confidence interval 0.89 to 3.88) (one trial, 230 participants, very low quality
      evidence). Preoperative transfusion versus no preoperative transfusion Two trials
      (434 participants) compared a preoperative transfusion plus standard care to a
      group receiving standard care. Overall, the quality of the evidence was low to
      very low across different outcomes according to GRADE methodology. This was due
      to the trials being at high risk of bias due to lack of blinding, and outcome
      estimates being imprecise. One trial was stopped early because more people in the
      no transfusion arm developed an acute chest syndrome.There was no difference in
      all-cause mortality between people receiving preoperative transfusions and those
      receiving no preoperative transfusions (two trials, 434 participants, no deaths
      occurred).There was significant heterogeneity between the two trials in the
      number of people developing an acute chest syndrome, a meta-analysis was
      therefore not performed. One trial showed a reduced number of people developing
      acute chest syndrome between people receiving preoperative transfusions and those
      receiving no preoperative transfusions, risk ratio 0.11 (95% confidence interval
      0.01 to 0.80) (65 participants), whereas the other trial did not, risk ratio 4.81
      (95% confidence interval 0.23 to 99.61) (369 participants).There were no
      differences between the preoperative transfusion groups and the groups without
      preoperative transfusion in the number of people developing:* a vaso-occlusive
      crisis, Peto odds ratio 1.91 (95% confidence interval 0.61 to 6.04) (two trials,
      434 participants, very low quality evidence).* a serious infection, Peto odds
      ratio 1.29 (95% confidence interval 0.29 to 5.71) (two trials, 434 participants,
      very low quality evidence);* any perioperative complications, risk ratio 0.24
      (95% confidence interval 0.03 to 2.05) (one trial, 65 participants, low quality
      evidence).There was an increase in the number of people developing circulatory
      overload in those receiving preoperative transfusions compared to those not
      receiving preoperative transfusions in one of the two trials, and no events were
      seen in the other trial (no meta-analysis performed). AUTHORS' CONCLUSIONS: There
      is insufficient evidence from randomised trials to determine whether conservative
      preoperative blood transfusion is as effective as aggressive preoperative blood
      transfusion in preventing sickle-related or surgery-related complications in
      people with HbSS disease. There is very low quality evidence that preoperative
      blood transfusion may prevent development of acute chest syndrome.Due to lack of
      evidence this review cannot comment on management for people with HbSC or
      HbSbeta(+) disease or for those with high baseline haemoglobin concentrations.

PMID- 27049333
TI  - The Natural Product Essramycin and Three of Its Isomers Are Devoid of
      Antibacterial Activity.
AB  - Four possible isomers of essramycin, a natural product from a marine Streptomyces
      species isolated from the Egyptian Mediterranean coast, were synthesized. The
      structures for the isomers were assigned unequivocally by (1)H NMR, (13)C NMR,
      high-resolution mass spectrometry, and X-ray crystal structure determinations.
      Notwithstanding the earlier report of broad-spectrum antibacterial activity for
      the natural product, none of the four isomers exhibited any such activity. 

PMID- 27049334
TI  - Nuclear Functions of Nucleolin through Global Proteomics and Interactomic
      Approaches.
AB  - Nucleolin (NCL) is a major component of the cell nucleolus, which has the ability
      to rapidly shuttle to several other cells' compartments. NCL plays important
      roles in a variety of essential functions, among which are ribosome biogenesis,
      gene expression, and cell growth. However, the precise mechanisms underlying NCL
      functions are still unclear. Our study aimed to provide new information on NCL
      functions via the identification of its nuclear interacting partners. Using an
      interactomics approach, we identified 140 proteins co-purified with NCL, among
      which 100 of them were specifically found to be associated with NCL after RNase
      digestion. The functional classification of these proteins confirmed the
      prominent role of NCL in ribosome biogenesis and additionally revealed the
      possible involvement of nuclear NCL in several pre-mRNA processing pathways
      through its interaction with RNA helicases and proteins participating in pre-mRNA
      splicing, transport, or stability. NCL knockdown experiments revealed that NCL
      regulates the localization of EXOSC10 and the amount of ZC3HAV1, two components
      of the RNA exosome, further suggesting its involvement in the control of mRNA
      stability. Altogether, this study describes the first nuclear interactome of
      human NCL and provides the basis for further understanding the mechanisms
      underlying the essential functions of this nucleolar protein.

PMID- 27049335
TI  - A First-Principle Study of Synergized O2 Activation and CO Oxidation by Ag
      Nanoparticles on TiO2(101) Support.
AB  - We performed density functional theory (DFT) calculations to investigate the
      synergized O2 activation and CO oxidation by Ag8 cluster on TiO2(101) support.
      The excellent catalytic activity of the interfacial Ag atoms in O2 dissociation
      is ascribed to the positive polarized charges, upshift of Ag d-band center, and
      assistance of surface Ti5c atoms. CO oxidation then takes place via a two-step
      mechanism coupled with O2 dissociation: (i) CO + O2 -> CO2 + O and (ii) CO + O ->
      CO2. The synergistic effect of CO and O2 activations reduces the oxidation energy
      barrier (Ea) of reaction (i), especially for the up-layered Ag atoms not in
      contact with support. It is found that the coadsorbed CO and O2 on the up-layered
      Ag atoms form a metal-stable four-center O-O-CO structure motif substantially
      promoting CO oxidation. On the oxygen defective Ag8/TiO2(101) surface, because of
      the decreased positive charges and the down-shift of d-band centers in Ag, the
      metal cluster exhibits low O2 adsorption and activation abilities. Although the
      dissociation of O2 is facilitated by the TiO2(101) defect sites, the dissociated
      O atoms would cover the defects so strongly that further CO oxidation would be
      prohibited unless much extra energy is introduced to recreate oxygen defects.

PMID- 27049336
TI  - Effects of cochlear implant surgical technique on post-operative electrode
      impedance.
AB  - CONCLUSIONS: The mCI surgical technique led to reduced impedance and minimized
      disturbance of the microenvironment inside the cochlea. Atraumatic surgical
      techniques and inflammation-reduction strategies may preserve the cochlear
      architecture and prevent fibrotic development. OBJECTIVES: To assess the
      advantages of a modified minimal access technique in cochlear implantation as
      well as to investigate the effects of intra-operative application of inflammation
      reduction strategies on the intra-cochlear impedance. METHODS: One hundred
      patients received a 31.5 mm long Med-El standard electrode array fully inserted
      into the cochlea and did not have surgical complications post-operation. Patients
      were divided into two groups according to the surgical technique that was used
      for implantation: 50 were in the modified minimal access cochlear implant (mCI)
      surgery group and 50 were in the traditional CI surgery group. Intra-cochlear
      impedance values were measured at initial activation (4 weeks post-operatively).
      Electrode impedance values were compared between the surgery groups. RESULTS:
      Electrode impedance values were significantly lower in the mCI group than in the
      CI surgery group at initial activation (5.01 kOhm vs 6.10 kOhm, respectively, F =
      13.761, p = 0.000). The differences between the two groups were most prominent
      for the electrodes located at the basal region of the cochlea.

PMID- 27049337
TI  - Daily impaired detachment and short-term effects of impaired sleep quality on
      next-day commuting near-accidents - an ambulatory diary study.
AB  - This study investigated the short-term effects of daily recovery, that is,
      impaired psychological detachment from work and various actigraphical indicators
      of sleep quality, on near-accidents when commuting to work the next morning.
      Furthermore, the mediating effect of actigraphically assessed sleep quality on
      the relationship between impaired psychological detachment from work and near
      accidents when commuting to work was analysed. Fifty-six full-time employees of a
      Swiss assurance company participated in the one-week study. Multilevel analyses
      revealed that impaired detachment was highly related to a decrease in sleep
      duration. Furthermore, impaired daily recovery processes, such as impaired
      psychological detachment from work and disturbed sleep quality, were related to
      commuting near-accidents. Impaired sleep quality mediated the effect of impaired
      psychological detachment from work on these near-accidents. Our results show that
      occupational safety interventions should address both impaired psychological
      detachment from work and sleep quality in order to prevent near accidents when
      commuting to work. Practitioner Summary: Commuting accidents occur frequently and
      have detrimental effects on employees, organisations and society. This study
      shows that daily lack of recovery, that is, impaired psychological detachment and
      impaired sleep quality, is related to near-accidents when commuting to work the
      next morning. Primary prevention of commuting accidents should therefore address
      daily lack of recovery. 

PMID- 27049339
TI  - Social-cognitive antecedents of hand washing: Action control bridges the planning
      behaviour gap.
AB  - OBJECTIVES: To examine motivational and volitional factors for hand washing in
      young adults, using the Health Action Process Approach (HAPA) as a theoretical
      framework. DESIGN: In a longitudinal design with two measurement points, six
      weeks apart, university students (N = 440) completed paper-based questionnaires.
      MAIN OUTCOME MEASURES: Prior hand washing frequency, self-efficacy, outcome
      expectancies, intention and action planning were measured at baseline, and coping
      planning, action control and hand washing frequency were measured at follow-up.
      RESULTS: A theory-based structural equation model was specified. In line with the
      HAPA, the motivational factors of self-efficacy and outcome expectancies
      predicted intention, whereas the volitional factors of planning and action
      control mediated between intention and changes in hand washing frequency. Action
      control was confirmed as the most proximal factor on hand washing behaviour, thus
      representing a bridge of the planning-behaviour gap. CONCLUSIONS: Both
      motivational and volitional processes are important to consider in the
      improvement of hand hygiene practices. Moreover, the statistically significant
      effects for planning and action control illustrate the importance of these key
      self-regulatory factors in the prediction of hand hygiene. The current study
      highlights the importance of adopting models that account for motivational and
      volitional factors to better understand hand washing behaviour.

PMID- 27049338
TI  - Receptivity to alcohol-related care among U.S. women Veterans with alcohol
      misuse.
AB  - Previous research indicates women Veterans have a potentially large, unmet need
      for alcohol-related care but are under-represented in treatment settings. The
      purpose of this study was to identify factors associated with women Veterans'
      receptivity to a recommendation for alcohol-related care when they present to
      Veterans Affairs (VA) primary care with alcohol misuse. Semi-structured
      interviews were conducted from 2012-2013 with 30 women Veterans at two VA
      facilities who screened positive for alcohol misuse during a primary care visit
      and discussed their alcohol use with their primary-care provider. Qualitative
      analyses identified 9 themes women used to describe what affected their
      receptivity to a recommendation for alcohol-related care (i.e., VA specialty
      substance use disorder services). The most common themes positively associated
      with women's receptivity included self-appraisal of their drinking behavior as
      more severe, the provider's presentation of treatment options, availability of
      gender-specific services, and worse physical and mental health. The themes
      identified here may have important implications for the clinical strategies
      providers can use to present alcohol-related care options to women Veterans to
      facilitate their use of care. These strategies include educating women about the
      health effects of alcohol misuse and increasing providers' knowledge about
      available care options (within the care organization or the community), including
      the availability of gender-specific services.

PMID- 27049340
TI  - Interactions of Some Divalent Metal Ions with Thymine and Uracil
      Thiosemicarbazide Derivatives.
AB  - The study of interactions between metal ions and nucleobases, nucleosides,
      nucleotides, or nucleic acids has become an active research area in chemical,
      biological, and therapeutic fields. In this respect, the coordination behavior of
      nucleobase derivatives to transition metals was studied in order to get a better
      understanding about DNA-metal interactions in in vitro and in vivo systems. Two
      nucleobase derivatives, 3-benzoyl-1-[3-(thymine-1-yl)propamido]thiourea and 3
      benzoyl-1-[3-(uracil-1-yl)propamido]thiourea, were synthesized and their
      dissociation constants were determined at different temperatures and 0.3 ionic
      strength. Potentiometric studies were carried out on the interaction of the
      derivatives towards some divalent metals in 50% v/v ethanol-water containing 0.3
      mol.dm(-3) KCl, at five different temperatures. The formation constants of the
      metal complexes for both ligands follow the order: Cu(2+) > Ni(2+) > Co(2+) >
      Zn(2+) > Pb(2+) > Cd(2+) > Mn(2+). The thermodynamic parameters were estimated;
      the complexation process has been found to be spontaneous, exothermic, and
      entropically favorable. 

PMID- 27049344
TI  - Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a
      ligand-dependent fashion.
AB  - Estrogen receptor alpha (ERalpha) has been implicated in several cell cycle
      regulatory events and is an important predictive marker of disease outcome in
      breast cancer patients. Here, we aimed to elucidate the mechanism through which
      ERalpha influences proliferation in breast cancer cells. Our results show that
      ERalpha protein is cell cycle-regulated in human breast cancer cells and that the
      presence of 17-beta-estradiol (E2) in the culture medium shortened the cell cycle
      significantly (by 4.5 hours, P < 0.05) compared with unliganded conditions. The
      alterations in cell cycle duration were observed in the S and G2/M phases,
      whereas the G1 phase was indistinguishable under liganded and unliganded
      conditions. In addition, ERalpha knockdown in MCF-7 cells accelerated mitotic
      exit, whereas transfection of ERalpha-negative MDA-MB-231 cells with exogenous
      ERalpha significantly shortened the S and G2/M phases (by 9.1 hours, P < 0.05)
      compared with parental cells. Finally, treatment of MCF-7 cells with
      antiestrogens revealed that tamoxifen yields a slower cell cycle progression
      through the S and G2/M phases than fulvestrant does, presumably because of the
      destabilizing effect of fulvestrant on ERalpha protein. Together, these results
      show that ERalpha modulates breast cancer cell proliferation by regulating events
      during the S and G2/M phases of the cell cycle in a ligand-dependent fashion.
      These results provide the rationale for an effective treatment strategy that
      includes a cell cycle inhibitor in combination with a drug that lowers estrogen
      levels, such as an aromatase inhibitor, and an antiestrogen that does not result
      in the degradation of ERalpha, such as tamoxifen.

PMID- 27049345
TI  - Submucosal tunneling endoscopic resection for tumors of the esophagogastric
      junction.
AB  - BACKGROUND: For submucosal tumors (SMTs) originating from the muscularis propria
      (MP) layer of the esophagogastric junction (EGJ), submucosal tunneling endoscopic
      resection (STER) is now widely used, and it shows promise in overcoming the
      limitations of endoscopic submucosal dissection. AIMS: This study aimed to
      evaluate the efficacy and safety of the STER technique for treating SMTs of the
      EGJ originating from the MP layer. MATERIAL AND METHODS: From October 2011 to
      February 2014, 20 patients were enrolled for STER surgery. RESULTS: The patients
      were categorized into three groups according to the tumor location. The
      esophagocardiac group had a lower complication rate (0/7) compared with the
      cardiac group (3/6) and the gastrocardiac group (3/7). The mean operation time in
      the esophagocardiac (83 +/- 24 min) and cardiac (83 +/- 55 min) groups was
      significantly shorter than that of the gastrocardiac group (145 +/- 44 min) (P <
      0.05). The en bloc resection rate was 100%, with no severe complications and no
      recurrence during the follow-up period. CONCLUSIONS: The STER technique appears
      to be a feasible and safe minimally invasive approach for SMTs originating from
      the MP layer of the EGJ, with satisfying en bloc resection, a short operation
      time, and low rates of severe complications.

PMID- 27049346
TI  - Allicin relaxes isolated mesenteric arteries through activation of PKA-KATP
      channel in rat.
AB  - Allicin is a natural effective organosulfur compound isolated from garlic, which
      possesses many beneficial properties, such as antibacterial, anti-inflammatory,
      antimicrobial, hypotensive and hypolipidemic. In the present study, we
      investigated the effects and the underlying mechanisms of allicin on isolated
      mesenteric arteries (MAs). We examined MAs relaxation induced by allicin on rat
      isolated mesenteric artery (MA) rings, the KATP channels with patch, and the
      expression of Kir6.1 and SUR2B with western blotting and NO production with
      Diaminofluorescein-FM diacetate (DAF-FMDA) in rat mesenteric artery smooth muscle
      cells (MASMCs). The results showed that allicin elicited the dose-dependent
      vasorelaxation effect with phenylephrine (PE) precontracted rat MA rings. The
      vasorelaxation effect was endothelium and NO independent but could be diminished
      by inhibition of PKA and KATP channels in the vascular smooth muscle. Allicin
      activated KATP channels in rat MASMCs, and the activation of KATP channels was
      inhibited by the inhibitors of PKA and KATP channels. But allicin had no effect
      on the expression of KATP subtypes Kir6.1 and SUR2B. These observations suggest
      that allicin exerts vasorelaxation effect through activation of PKA-KATP
      signaling pathway.

PMID- 27049347
TI  - Depressive symptoms and muscular fitness contribute independently to the ability
      to perform daily life activities in people with bipolar disorder.
AB  - BACKGROUND: Compared with healthy controls, people with bipolar disorder
      experience muscle weakness. The extent to which muscle weakness influences the
      performance of daily life activities such as walking in people with bipolar
      disorder requiring hospitalization is unclear. AIMS: The primary aim of the
      current study was to explore whether depressive symptoms and muscular fitness
      independently contribute to the walking capacity in people with bipolar disorder.
      A secondary aim was to identify variables that could explain the variability in
      muscular fitness. METHODS: Forty-two inpatients with bipolar disorder performed a
      standing broad jump test (SBJ), a measure of muscular performance, and the six
      minute walk test (6MWT) in addition to the International Physical Activity
      Questionnaire (IPAQ), the Depressive Symptomatology Self Report (QIDS) and a full
      fasting metabolic screening. RESULTS: The correlation between the 6MWT (595.0 +/-
      127.3m) and SBJ (126.2 +/- 48.6m) was high (r = 0.72, p < 0.001). In backward
      regression analyzes, 82.3% of the variance in 6MWT was explained by SJB, QIDS
      (7.6 +/- 5.1) and the presence of metabolic syndrome (n = 16; 38%), while 83.0%
      of the variance in SBJ-score was explained by age, and the QIDS and IPAQ (1435.3
      +/- 1179.8 MET-min/week) scores. CONCLUSIONS: Depressive symptoms and muscular
      fitness contribute independently to daily life functioning in people with bipolar
      disorder. Thus, muscular rehabilitation strategies might offer a strategy for
      improving performance of daily life activities in this group.

PMID- 27049348
TI  - Does Viewing Pornography Diminish Religiosity Over Time? Evidence From Two-Wave
      Panel Data.
AB  - Research consistently shows a negative association between religiosity and
      viewing pornography. While scholars typically assume that greater religiosity
      leads to less frequent pornography use, none have empirically examined whether
      the reverse could be true: that greater pornography use may lead to lower levels
      of religiosity over time. I tested for this possibility using two waves of the
      nationally representative Portraits of American Life Study (PALS). Persons who
      viewed pornography at all at Wave 1 reported more religious doubt, lower
      religious salience, and lower prayer frequency at Wave 2 compared to those who
      never viewed porn. Considering the effect of porn-viewing frequency, viewing porn
      more often at Wave 1 corresponded to increases in religious doubt and declining
      religious salience at Wave 2. However, the effect of earlier pornography use on
      later religious service attendance and prayer was curvilinear: Religious service
      attendance and prayer decline to a point and then increase at higher levels of
      pornography viewing. Testing for interactions revealed that all effects appear to
      hold regardless of gender. Findings suggest that viewing pornography may lead to
      declines in some dimensions of religiosity but at more extreme levels may
      actually stimulate, or at least be conducive to, greater religiosity along other
      dimensions.

PMID- 27049349
TI  - Causal judgements about temporal sequences of events in single individuals.

PMID- 27049350
TI  - Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits
      tumor progression and angiogenesis.
AB  - Several angiogenesis inhibitors targeting the vascular endothelial growth factor
      (VEGF) signaling pathway have been approved for cancer treatment. However, VEGF
      inhibitors alone were shown to promote tumor invasion and metastasis by
      increasing intratumoral hypoxia in some preclinical and clinical studies.
      Emerging reports suggest that Delta-like ligand 4 (Dll4) is a promising target of
      angiogenesis inhibition to augment the effects of VEGF inhibitors. To evaluate
      the effects of simultaneous blockade against VEGF and Dll4, we developed a
      bispecific antibody, HD105, targeting VEGF and Dll4. The HD105 bispecific
      antibody, which is composed of an anti-VEGF antibody (bevacizumab-similar)
      backbone C-terminally linked with a Dll4-targeting single-chain variable
      fragment, showed potent binding affinities against VEGF (KD: 1.3 nM) and Dll4
      (KD: 30 nM). In addition, the HD105 bispecific antibody competitively inhibited
      the binding of ligands to their receptors, i.e., VEGF to VEGFR2 (EC50: 2.84 +/-
      0.41 nM) and Dll4 to Notch1 (EC50: 1.14 +/- 0.06 nM). Using in vitro cell-based
      assays, we found that HD105 effectively blocked both the VEGF/VEGFR2 and
      Dll4/Notch1 signaling pathways in endothelial cells, resulting in a conspicuous
      inhibition of endothelial cell proliferation and sprouting. HD105 also suppressed
      Dll4-induced Notch1-dependent activation of the luciferase gene. In vivo
      xenograft studies demonstrated that HD105 more efficiently inhibited the tumor
      progression of human A549 lung and SCH gastric cancers than an anti-VEGF antibody
      or anti-Dll4 antibody alone. In conclusion, HD105 may be a novel therapeutic
      bispecific antibody for cancer treatment.

PMID- 27049351
TI  - Testicular Growth During Puberty in Boys With and Without a History of Congenital
      Cryptorchidism.
AB  - CONTEXT: The pattern of testicular growth during puberty may provide important
      information about early testicular damage and reproductive potential in
      adulthood. OBJECTIVE: To evaluate pubertal testicular growth in boys with
      congenital cryptorchidism and controls. DESIGN: Longitudinal case-control study.
      SETTING: Andrological Research Center, University of Turku. PARTICIPANTS:
      Altogether, 119 boys participated: 51 cases with a history of congenital
      cryptorchidism and 65 controls fulfilled the inclusion criteria. INTERVENTION:
      None. MAIN OUTCOME MEASURES: Testicular volume by an orchidometer (mL) and
      ultrasound (mL), testicular length by a ruler (mm), and onset of pubertal
      testicular growth (y). Longitudinal testicular growth was analyzed with a
      nonlinear mixed-effect model. RESULTS: The mean age of the onset of pubertal
      testicular growth (age at the attainment of >3 mL by orchidometer) was 11.7 and
      11.8 years in cryptorchid cases and controls, respectively. The difference
      between cases and controls was not significant. Modeled postpubertal testicular
      size was smaller among bilaterally and unilaterally undescended testis than in
      controls. There was a high level of agreement between testicular sizes of 3 mL by
      orchidometer and 25 mm by ruler as cut-offs in definition of the onset of
      puberty. An orchidometer size of 3 mL and ruler length of 25 mm corresponded to
      1.6 and 1.7 mL by ultrasound (with Lambert's formula), respectively. CONCLUSIONS:
      Testicular growth in puberty was impaired in congenitally cryptorchid boys. This
      suggests a poor perinatal development of the cryptorchid testis. The timing of
      the onset of pubertal testicular growth, however, did not differ which suggests
      an intact hypothalamic-pituitary axis.

PMID- 27049352
TI  - The challenges of screening pre-school children for autism spectrum disorders in
      Iran.
AB  - PURPOSE: Early identification and diagnosis of children with autism spectrum
      disorder is recommended, but this is difficult to achieve in less developed
      countries due to a lack of suitable tools and personnel. This two-phase study,
      undertaken in Iran, aimed to develop culturally appropriate and feasible means
      for screening pre-school children for autism spectrum disorder (ASD). METHOD: The
      first phase involved information and training events held in four cities to alert
      parents and to recruit and train professionals to undertake screenings and
      diagnostic assessments. In phase 2, a screening tool developed in Iran was
      administered to over 20 000 preschool children with the Iranian version of the
      GARS2 scale used to assess the probability of the child having ASD. RESULTS: Over
      250 professionals were trained and assessed as competent screeners of whom a
      further 67 were trained and accredited to use GARS2. They included postgraduate
      students and practitioners from a range of disciplines. In all, 1579 children
      screened positive; however, only 130 parents brought their child for the
      diagnostic assessment of whom 22% had a high probability of having ASD.
      CONCLUSION: The feasibility of undertaking a screening programme for ASD with
      Iranian preschoolers has been demonstrated although further research is needed to
      refine the screening and diagnostic tools, monitor assessors and promote greater
      engagement of families. Implications for Rehabilitation Sizeable numbers of
      postgraduate students and practitioners were recruited to assist with the
      screening and assessments of preschoolers. The uptake of screening was highest
      among parents of four and five years olds but much less so for younger children
      and in bringing children for further assessments. Further research is needed into
      the development of more suitable screening and diagnostic tools for ASD with
      Iranian preschoolers and the training of assessors in their use.

PMID- 27049353
TI  - Actual use of and satisfaction associated with rollators and "shopping carts"
      among frail elderly Japanese people using day-service facilities.
AB  - Purpose This study aimed at clarifying the actual use of and satisfaction with
      rollators and "shopping carts" (wheeled walkers with storage) among frail elderly
      people, who were certified by a long-term care insurance system as users of
      facilities that provide day-service nursing care and rehabilitation. Methods We
      identified 1247 frail elderly people who used day-service facilities, and
      evaluated their actual use of, and satisfaction with, rollators and shopping
      carts. Results Forty-four (3.5%) individuals used rollators, and 53 (4.3%) used
      shopping carts. The shopping cart group contained more individuals who were
      certified as care level 1 (26.4%), than the rollator group (20.5%), and 52.8% of
      the shopping cart group was certified as care levels 1-3. The scores for "repairs
      and services" and "follow-up" from the Quebec User Evaluation of Satisfaction
      with assistive Technology second version (QUEST 2.0) survey were significantly
      higher in the rollator group than in the shopping cart group. Conclusions The
      QUEST 2.0 scores revealed that shopping cart users exhibit insufficient "repairs
      and services" and "follow-up" scores. As frail elderly people with poor care
      status accounted for >50% of the shopping cart group, these individuals urgently
      need walking aids that are tailored to their care status. Implications for
      Rehabilitation We conclude that walking aid fitting must be tailored to each
      persons care status, and suggest that a system should be established to allow
      occupational or physical therapists to provide this fitting Moreover, our
      analysis of the QUEST2.0 service scores revealed that repairs, services, and
      follow-up are insufficient to meet the needs of shopping cart users.

PMID- 27049355
TI  - The electronic band structures of gadolinium chalcogenides: a first-principles
      prediction for neutron detecting.
AB  - By converting the energy of nuclear radiation to excited electrons and holes,
      semiconductor detectors have provided a highly efficient way for detecting them,
      such as photons or charged particles. However, for detecting the radiated
      neutrons, those conventional semiconductors hardly behave well, as few of them
      possess enough capability for capturing these neutral particles. While the
      element Gd has the highest nuclear cross section, here for searching proper
      neutron-detecting semiconductors, we investigate theoretically the Gd
      chalcogenides whose electronic band structures have never been characterized
      clearly. Among them, we identify that gamma-phase Gd2Se3 should be the best
      candidate for neutron detecting since it possesses not only the right bandgap of
      1.76 eV for devices working under room temperature but also the desired indirect
      gap nature for charge carriers surviving longer. We propose further that
      semiconductor neutron detectors with single-neutron sensitivity can be realized
      with such a Gd-chalcogenide on the condition that their crystals can be grown
      with good quality. 

PMID- 27049354
TI  - Effect of vaginal cleansing on postoperative factors in elective caesarean
      sections: a prospective, randomised controlled trial.
AB  - OBJECTIVE: To assess the effect of povidone iodine versus benzalkonium chloride,
      which were applied preoperatively for vaginal disinfection in caesarean sections,
      on postoperative factors. METHODS: One hundred and twenty patients underwent
      elective caesarean section were divided into three groups using the simple
      randomisation method: Group 1 (povidone iodine, n: 41); Group 2 (benzalkonium
      chloride, n: 39); Group 3 (control group, n: 40). Demographic data, duration of
      operation, amount of bleeding, postoperative pain, time to first flatulence and
      defaecation, haematological parameters on postoperative day 1 were compared
      between three groups. Pain evaluation was performed at 6th and 24th postoperative
      hour using Visual Analogue Scale. RESULTS: No statistically significant
      differences were detected between the groups in demographic characteristics.
      There were no significant differences between the groups with respect to the
      duration of operation and hospital stay. The patients in the group who underwent
      povidone iodine vaginal cleansing had statistically significantly less
      postoperative pain as compared to control group. No difference was observed
      between the groups in haematological parameters other than C-reactive protein
      (CRP); however, CRP levels at 24th post-operative hour were significantly lower
      in Group 1 compared to the other groups. CONCLUSIONS: The preoperative vaginal
      cleansing with povidone iodine could reduce the postoperative pain, analgesic
      need and infection parameter.

PMID- 27049356
TI  - Perceived and Objectively Measured Environmental Correlates of Domain-Specific
      Physical Activity in Older English Adults.
AB  - We examine the relative importance of both objective and perceived environmental
      features for physical activity in older English adults. Self-reported physical
      activity levels of 8,281 older adults were used to compute volumes of outdoor
      recreational and commuting activity. Perceptions of neighborhood environment
      supportiveness were drawn from a questionnaire survey and a geographical
      information system was used to derive objective measures. Negative binominal
      regression models were fitted to examine associations. Perceptions of
      neighborhood environment were more associated with outdoor recreational activity
      (over 10% change per standard deviation) than objective measures (5-8% change).
      Commuting activity was associated with several objective measures (up to 16%
      change). We identified different environmental determinants of recreational and
      commuting activity in older adults. Perceptions of environmental supportiveness
      for recreational activity appear more important than actual neighborhood
      characteristics. Understanding how older people perceive neighborhoods might be
      key to encouraging outdoor recreational activity.

PMID- 27049357
TI  - The New Brazilian Journal of Nephrology (BJN).

PMID- 27049358
TI  - Averting the legacy of kidney disease-focus on childhood.
AB  - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents
      of adult kidney disease that can begin in earliest childhood. Chronic kidney
      disease (CKD) in childhood differs from that in adults, as the largest diagnostic
      group among children includes congenital anomalies and inherited disorders, with
      glomerulopathies and kidney disease in the setting of diabetes being relatively
      uncommon. In addition, many children with acute kidney injury will ultimately
      develop sequelae that may lead to hypertension and CKD in later childhood or in
      adult life. Children born early or who are small-for date newborns have
      relatively increased risk for the development of CKD later in life. Persons with
      a high-risk birth and early childhood history should be watched closely in order
      to help detect early signs of kidney disease in time to provide effective
      prevention or treatment. Successful therapy is feasible for advanced CKD in
      childhood; there is evidence that children fare better than adults, if they
      receive kidney replacement therapy including dialysis and transplantation, while
      only a minority of children may require this ultimate intervention Because there
      are disparities in access to care, effort is needed so that those children with
      kidney disease, wherever they live, may be treated effectively, irrespective of
      their geographic or economic circumstances. Our hope is that World Kidney Day
      will inform the general public, policy makers and caregivers about the needs and
      possibilities surrounding kidney disease in childhood. 

PMID- 27049359
TI  - Renal inflammatory and oxidative and metabolic changes after 6 weeks of cafeteria
      diet in rats.
AB  - INTRODUCTION: Obesity is a disease in which inflammation is directly involved and
      can lead to impaired renal function. OBJECTIVE: To evaluate the influence of
      short term exposure to cafeteria diet on kidney tissue inflammation and advanced
      glycation end products (AGEs) in the rat plasma. METHODS: Male Wistar rats (10
      weeks of age, weighing 350 g) were assigned to receive commercial chow diet (C; n
      = 8 animals/group, 5% of energy from fat) or cafeteria diet (CAF-D, n = 8
      animals/group: 29% energy fat) and sucrose in drinking water (300 g/L) for 6
      weeks. RESULTS: adiposity index at six weeks was higher in CAF-D group compared
      to C. The same behavior was observed for plasma levels of glucose, triglycerides,
      leptin, insulin and AGEs. The gene expression of IL-6 and TNF-alpha in renal
      tissue was higher in CAF-D group and no significant difference in adipose tissue.
      There was no increase of these cytokines in plasma and kidney or histologically.
      There was a significant decrease of adiponectin in the CAF-D group. CONCLUSION:
      The short exposure CAF-D reflects changes in metabolism, increased plasma levels
      of AGEs, which may reflect the increased expression of inflammatory cytokines in
      the kidney.

PMID- 27049360
TI  - Creatinine measurement on dry blood spot sample for chronic kidney disease
      screening.
AB  - INTRODUCTION: Chronic kidney disease (CKD) screening is advisable due to its high
      morbidity and mortality and is usually performed by sampling blood and urine.
      OBJECTIVE: Here we present an innovative and simpler method, by measuring
      creatinine on a dry blood spot on filter paper. METHODS: One-hundred and six
      individuals at high risk for CKD were enrolled. The creatinine values obtained
      using both tests and the demographic data of each participant allowed us to
      determinate the eGFR. The adopted cutoff for CKD was an eGFR < 60 ml/min.
      RESULTS: Mean age was 57 +/- 12 years, 74% were female, 40% white, and 60% non
      white. Seventy-six percent were hypertensive, 30% diabetic, 37% had family
      history of CKD, and 22% of smoking. The BMI was 29.5 +/- 6.9 kg/m2, median
      systolic blood pressure was 125 mmHg (IQR 120-140 mmHg) and median diastolic
      blood pressure was 80 mmHg (IQR 70-80 mmHg). According to MDRD equation,
      sensitivity was 96%, specificity 55%, predictive positive value 96%, predictive
      negative value 55% and accuracy 92%. By the CKD-EPI equation the sensitivity was
      94%, specificity 55%, predictive positive value 94%, predictive negative value
      55% and accuracy 90%. A Bland and Altman analysis showed a relatively narrow
      range of creatinine values differences (+ 0.68mg/dl to -0.55mg/dl) inside the +/-
      1.96 SD, without systematic differences. CONCLUSION: Measurement of creatinine on
      dry blood sample is an easily feasible non-invasive diagnostic test with good
      accuracy that may be useful to screen chronic kidney disease.

PMID- 27049362
TI  - Montreal Cognitive Assessment (MoCA) screening mild cognitive impairment in
      patients with chronic kidney disease (CKD) pre-dialysis.
AB  - INTRODUCTION: Individuals with chronic kidney disease (CKD) are at higher risk of
      developing cognitive impairment (CI), initially mild (MCI), potentially
      identifiable, but still poorly diagnosed and treated. The Montreal Cognitive
      Assessment (MoCA) has been indicated for MCI screening in CKD. OBJECTIVE: To
      assess MCI in patients with CKD not yet on dialysis. METHODS: Study conducted in
      72 non-elderly subjects with pre-dialysis CKD. The neuropsychological assessment
      included: The global cognitive assessment test MoCA; the clock drawing (CD); the
      digit span forward (DSF) and reverse (DSR); phonemic verbal (VF) fluency (FAS)
      and semantics (animals); the fist-edge-palm (FEP); and the memory 10 pictures.
      RESULTS: The average age of the participants was 56.74 +/- 7.63 years, with
      predominance of male sex (55.6%), mainly with >= 4 years of education (84.3%),
      with CKD cathegories 1, 2 and 3a and 3b (67.6%), hypertension (93.1%) and
      diabetes mellitus (52.1%). MCI (MoCA <= 24) was observed in 73.6% of the
      patients. We did not find association among MCI with demographic and clinical
      variables, but a tendency to association with age (p = 0.07), educational level
      (p= 0.06) and diabetes (0.06). The executive function tests CD, DS-reverse and
      FEP, individually were able to identify CI with good sensibility and negative
      predictive value compared to MoCA and together, showed the same capability to
      identify MCI when compared to MoCA. CONCLUSION: The MCI is common in non-elderly
      patients with CKD not yet on dialysis. Together, the CD, DSR and FEP showed
      similar performance in identify MCI in this population when compared to MoCA,
      suggesting impairment of executive functions.

PMID- 27049361
TI  - Prevalence of chronic renal disease in adults attended by the family health
      strategy.
AB  - INTRODUCTION: Chronic Kidney Disease (CKD) is an important Brazilian public
      health issue that has as main etiologies, arterial hypertension and diabetes
      mellitus (DM). The precocious diagnosis is important, because it allows the
      implementation of preventive measures that retard or interrupt the progression to
      the most advanced stages of the CKD. OBJECTIVE: Identify the prevalence and the
      associated factors to the CKD among adults served by the Family Health Strategy
      (FHS). METHODS: Cross-sectional study with epidemiological, descriptive and
      observational design, realized with 511 adults older than 20 years, served by the
      FSH in a region of Goiania. CKD was defined as GFR < 60 mL/min/1.73m(2) and/or
      albuminuria >= 30 mg/g. The GFR was estimated by the Cockcroft-Gault equation and
      albuminuria by the ratio of albumin and urinary creatinine in the urine sample.
      The independent variables were age, sex, blood pressure, alcohol comsumption, DM,
      smoking and overweight/obesity. RESULTS: The CKD prevalence was 32,53%. While GFR
      < 60ml/min/1.73 m(2) occurred in 10,64% and albuminuria in 25,29% of the sample.
      The analysis identified a significant association between the ages >= 60 and GFR
      < 60ml/min/1.73 m2 (p < 0,001); as the albuminuria >= 30 mg/g the association was
      found in the male gender (p = 0,043), DM (p = 0,002) and alcohol consumption (p =
      0,035). CONCLUSION: There was a high prevalence of CKD's early stages on FHS,
      taking in consideration the risk factors of age >= 60 years old, masculine
      gender, DM and alcohol consume. Therefore, a CKD screening and monitoring is
      suggested in adults who are served by the FHS.

PMID- 27049363
TI  - Frequency and clinical histological analysis of glomerular diseases in a tertiary
      hospital in southern Brazil.
AB  - INTRODUCTION: The glomerulopathies are the most common biopsy-proven kidney
      diseases. The epidemiological investigation of glomerulopathies allows the
      identification of their distribution and main causes and enables the development
      of prevention and treatment strategies. OBJECTIVE: This study aims to identify
      the frequency and clinical-pathological correlation of glomerular diseases
      diagnosed at the HC-UFPR over the period of 5 years. METHODS: 131 biopsies were
      performed between January 1, 2008 and December 31, 2012 and were analysed by
      light and immunofluorescence microscopy. Histopathological slides were reviewed
      by a pathologist. Clinical and laboratory data and the immunofluorescence
      microscopy results were extracted from medical records. The findings were
      tabulated and analysed. RESULTS: 128 of 131 cases were reanalysed. 46.5% were
      obtained from men. Patients' age averaged 43 years for men and 38 for women. In
      99 cases, the indication of biopsy was identified; 49.5% cases presented
      nephrotic syndrome, 17.17%, acute renal failure and 15.15%, chronic renal
      failure; 8.08%, nephritic syndrome; 6.06%, isolated proteinuria and 4.04%
      isolated hematuria. In 61.21% an underlying disease related to the glomerulopathy
      could be identified; 33.62% corresponded to primary disease and in 5.17% of cases
      the nature of the glomerulopathy could not be determined. Among secondary
      glomerulopathies, the most frequent was Lupus Nephritis (49.29%), and among the
      primary, Focal Segmental Glomerulosclerosis (30.77%) and Membranous Nephropathy
      (25.64%). CONCLUSION: The average patient with glomerulopathy in this service is
      an adult with nephrotic syndrome. Unlike other reports, secondary
      glomerulopathies were predominant. These findings may reflect the tertiary
      characteristic of the assistance at HC-UFPR.

PMID- 27049364
TI  - Podocyturia in Fabry disease.
AB  - INTRODUCTION: Fabry disease is a lysosomal storage disorder due to abnormalities
      in the GLA gene (Xq22). Such changes result in the reduction/absence of activity
      of the lysosome enzyme alpha-GAL, whose function is to metabolize
      globotriaosylceramide (Gb3). Renal disease is a major clinical outcome of the
      accumulation of Gb3. Podocyte injury is thought to be a major contributor to the
      progressive loss of the renal function and may be found altered even before the
      onset of microalbuminuria. OBJECTIVE: The aim of this study was to quantify the
      urinary excretion of podocytes in Fabry disease patients (V269M, n = 14) and
      healthy controls (n = 40), and to correlate podocyturia with the variables
      gender, age, time of therapy and albumin: creatinine ratio (ACR). METHODS:
      Urinary podocytes were stained using immunofluorescence to podocalyxin and DAPi.
      The number of podocalyxin-positive cells was quantified and the average number
      was taken (normal range 0-0.6 podocytes/mL). RESULTS: The average number of
      podocytes in the urine of Fabry disease patients was significantly higher than in
      healthy controls (p < 0.0001). We observed a positive correlation between
      podocyturia and ACR (p = 0.004; (r2 = 0.6417). We found no correlation between
      podocyturia and gender, age or duration of therapy. CONCLUSION: Podocyturia is an
      important parameter in the assessment of renal disease in general, and it may
      serve as an additional early tool for monitoring Fabry disease nephropathy even
      before changes in ACR are seen. This may prove to be a useful tool to assess
      disease progression in patients expected to have a more aggressive phenotype.

PMID- 27049365
TI  - Brazilian Chronic Dialysis Census 2014.
AB  - INTRODUCTION: National chronic dialysis data have had impact in the treatment
      planning. OBJECTIVE: To report data of the annual survey of the Brazilian Society
      of Nephrology about chronic kidney disease patients on dialysis in July 2014.
      METHODS: A survey based on data of dialysis units from the whole country. The
      data collection was performed by using a questionnaire filled out on-line by the
      dialysis units. RESULTS: Three hundred twelve (44%) of the dialysis units in the
      country answered the questionnaire. In July 2014, the total estimated number of
      patients on dialysis was 112,004. The estimated prevalence and incidence rates of
      chronic maintenance dialysis were 552 (range: 364 in the North region and 672 in
      the Southeast) and 180 patients per million population (pmp), respectively. The
      annual incidence rate of patients with diabetic nephropathy was 77 pmp. The
      annual gross mortality rate was 19%. For prevalent patients, 91% were on
      hemodialysis and 9% on peritoneal dialysis, 32,499 (29%) were on a waiting list
      of renal transplant, 37% were overweight/obese, 29% were diabetics, 16% had PTH
      levels > 600 pg/ml and 26% hemoglobin < 10 g/dl. A venous catheter was the
      vascular access for 17% of the hemodialysis patients. CONCLUSION: During 2011
      2014 the prevalence and incidence rates of patients on dialysis tended to
      increase, while the gross mortality rate remained stable. In 2014, diabetes was
      the primary renal disease in 42% of the new dialysis patients.

PMID- 27049366
TI  - Variability in quality of care among dialysis units in the state of Sao Paulo and
      the ordinance number 389/2014 of the Health Ministry of Brazil.
AB  - INTRODUCTION: Medical organizations have proposed indices to assess the quality
      of dialytic therapy offered to patients with chronic kidney disease (CKD).
      Recently, the Ministry of Health of Brazil published the ordinance n degrees 
      389/2014, which establishes targets in the care of patients with CKD. OBJECTIVE:
      We evaluate the performance of hemodialysis (HD) clinics in relation to the goals
      established in this ordinance. METHODS: Cross-sectional study, prospective,
      observational, involving 1,633 patients with CKD on HD in eight clinics.
      Demographic characteristics, Kt/V, hemoglobin, phosphorus, parathormone (PTH) and
      the mortality rate were recorded. The results were compared to the goals
      established in the ordinance No. 389/2014: Kt/V > 1.2 in more than 70% of
      patients, hemoglobin between 10 and 12 g/dl in more than 80%, phosphorus between
      3.5 and 5.5 mg/dl in more than 50%, and PTH < 600pg/ml in more than 80% of
      patients. RESULTS: The age was 56.4 +/- 15.2 years, the median time on dialysis
      was 28.4 months. The HD session time was 3.74 +/- 0.31 hours. For Kt/V, six
      clinics reached the goal. For hemoglobin, none of the clinics reached the goal.
      For phosphorus, only two clinics meet the goal and for PTH four clinics. Six
      clinics hit two goals and two clinics did not achieve any goal. Mortality was
      lower in clinics that reached targets (10.2vs. 21.6% per year; p = 0.0546).
      CONCLUSION: For Kt/V most clinics reached the goal established by the ordinance.
      For hemoglobin and phosphorus, the objectives were not achieved in many clinics.
      For PTH, the response was variable and dependent on clinical features.

PMID- 27049367
TI  - Hypoalbuminemia seems to be associated with a higher rate of hospitalization in
      hemodialysis patients.
AB  - INTRODUCTION: Anemia, inflammation and hypoalbuminemia are frequent disorders
      among patients underwent hemodialysis. There are few national data, particularly
      from Northeast region where anemia and malnourished were common findings,
      analyzing the association between these conditions and clinical outcomes.
      OBJECTIVE: The aim of this study was to evaluate the impact of the presence of
      anemia, inflammation and hypoalbuminemia on clinical outcomes (death and
      hospitalization) of hemodialysis patients. METHODS: In this prospective
      observational study 221 adult patients were evaluated, considering the presence
      of anemia (hemoglobin <= 10 g/dL), inflammation (C-reactive protein (CRP) >= 0,5
      mg/dL) and hypoalbuminemia (albumin < 3,8 g/ dL) at baseline. Clinical outcomes
      were recorded over 13 months. RESULTS: The occurrence of hospitalization and
      death did not differ between the groups with and without anemia or inflammation.
      Patients with hypoalbuminemia had more hospitalizations, and the presence of
      hypoalbuminemia was associated with shorter hospitalization event-free time (p =
      0.008). There was a trend of shorter hospitalization event-free time among
      patients with increased PCR (p = 0.08). There was no correlation between albumin
      and CRP levels. The presence of anemia, inflammation and hypoalbuminemia were not
      associated with lower survival. Adjusting for confounders, hypoalbuminemia was a
      predictor of hospitalization in hemodialyzed patients. CONCLUSION: The presence
      of hypoalbuminemia, but not anemia or inflammation, was able to predict
      hospitalization in hemodialysis patients.

PMID- 27049368
TI  - Anemia in patients undergoing ambulatory peritoneal dialysis: prevalence and
      associated factors.
AB  - INTRODUCTION: Anemia is a common complication in dialysis patients, scare studies
      have evaluated anemia in patients undergoing peritoneal dialysis (PD). OBJECTIVE:
      This study aimed to investigate the prevalence of anemia and its associated
      factors in patients undergoing PD in a single center where patients have free
      access to agents stimulating erythropoiesis (ESA) and intravenous iron
      supplementation. METHODS: Cross-sectional study analyzing the demographic,
      clinical and laboratory variables of 120 patients. Anemia was defined as
      hemoglobin (Hb) < 11 g/dl. RESULTS: Patients were on PD for 17 months, and the
      majority of them (86%) received automated PD. The mean age was 58 +/- 16.5 years,
      and 52% were female and 29% were diabetes. Anemia was present in 34 (28%)
      patients. When compared with those without anemia, patients with anemia received
      a higher dose of iron (p = 0.02) and had a lower concentration of triglycerides
      (p = 0.01). Hb levels correlated negatively with iron (r = -0.20;p = 0.03) and
      ESA (r = -0.23; p = 0.01) doses and positively with albumin (r = 0.38; p = 0.01),
      triglycerides (r = 0.24; p = 0.01) and transferrin saturation (r = 0.20; p =
      0.03). In multiple analyses, only the albumin concentration (beta = 0.84; 95% IC
      = 0.38-1.31;p < 0.001) and ESA dose (beta = -0.06; 95% IC = 0.00-0.00; p = 0.02)
      were independently associated with Hb levels. CONCLUSIONS: Almost 30% of PD
      patients had anemia, even with free access to erythropoietin and intravenous
      iron. The transferrin saturation and nutritional status assessed by albumin, were
      the factors associated with the occurrence of anemia in this population.

PMID- 27049369
TI  - Effect of induction therapy in kidney transplantation in sensitive patients:
      analysis of risks and benefits.
AB  - INTRODUCTION: Sensitization is associated with worse clinical outcomes after
      kidney transplantation (KT), including increased incidence of delayed graft
      function, acute rejection (AR) and graft loss. OBJECTIVES: To evaluate 1-year
      efficacy and safety outcomes in sensitized KT recipients receiving antithymocyte
      globulin (ATG) induction and compare them to non-sensitized patients. METHODS:
      Deceased donors KT recipients transplanted between January 1998 and December 2009
      were divided into 5 groups: control group 1 -n = 89, PRA negative, without
      induction therapy; control group 2 - n = 94, PRA negative, basiliximab induction;
      control group 3 - n = 81, PRA negative, ATG induction; test group 4 - n = 64, PRA
      1-49%, ATG induction; test group 5 -n = 118, PRA >= 50%, ATG induction. RESULTS:
      There was no difference in the incidence of AR among patients sensitized and non
      sensitized, except for group 1, with highest incidence of AR (20.2%,p = 0.006 vs.
      Group 4 and p = 0.001 vs. group 5). Sensitized patients induced with ATG had
      higher incidence of citomegalovirus infection when compared with group 2 (26.6%
      and 14.4% vs. 2.1%). There were no differences in graft and patient survivals. In
      multivariable analysis, PRA > 50% and ATG induction were not associated with
      graft loss, death or death-censored graft loss. CONCLUSION: Sensitized patients
      induced with ATG presented similar or lower incidence of AR when compared with
      non-sensitized patients not induced. Besides, these patients had similar safety
      profile and graft and patient survivals at 1 year.

PMID- 27049370
TI  - Pediatric urolithiasis: experience at a tertiary care pediatric hospital.
AB  - INTRODUCTION: Pediatric urolithiasis has become more prevalent in recent decades,
      with high recurrence rates and considerable morbidity. Most children with
      idiopathic urolithiasis have an underlying metabolic abnormality and proper
      research provides therapeutic interventions to reduce the formation of new stones
      and its complications. OBJECTIVE: To identify demographic and clinical
      characteristics of pediatric urolithiasis, etiology, treatment management,
      disease recurrence and patient outcomes in a tertiary care pediatric hospital.
      METHODS: A retrospective descriptive study of pediatric patients admitted to the
      Hospital Infantil Joana de Gusmao in Florianopolis, SC, Brazil, who were
      diagnosed with urolithiasis, from January 2002 to December 2012. Data were
      obtained from medical records. Those patients with diagnosis confirmed by imaging
      and 24hr urine or single sample urine were included. RESULTS: We evaluated 106
      pediatric patients (65% M). Average age at diagnosis was 8.0 +/- 4.2 and 85% of
      them had positive family history of urolithiasis. Abdominal pain, renal colic and
      urinary tract infection were the main manifestations. 93.2% had metabolic
      abnormality and hypercalciuria was the most common. Pharmacological treatment was
      established in 78% of cases. Potassium citrate and hydrochlorothiazide were used.
      Surgical treatment was performed in 38% of patients. There was response to
      treatment in 39% of patients with recurrence of urolithiasis in 34.2% of them.
      Only 4.7% of patients continued follow-up, 6.6% were referred to other services,
      8.5% were discharged and 73.8% lost follow-up. CONCLUSION: Pediatric urolithiasis
      deserves a detailed metabolic evaluation after their initial presentation for
      treatment, monitoring and prevention of its formation and its complications.

PMID- 27049371
TI  - Therapy of nephrolithiasis: where is the evidence from clinical trials?
AB  - The prevalence of kidney stone disease is increasing worldwide with significant
      health and economic burden. Newer research is finding that stones are associated
      with several serious morbidities. Yet, few randomized clinical trials or high
      quality observational studies have assessed whether clinical interventions
      decrease the recurrence of kidney stones. Therefore, in this review we analyze
      the available evidence on medical expulsive therapy for ureteral stones; describe
      the evidence about non-pharmacological stone therapy including dietary
      modifications and citrus juice-based therapy; and discuss the efficacy of
      thiazide diuretics for the treatment of hypercalciuria in recurrent
      nephrolithiasis. 

PMID- 27049372
TI  - Pathogenesis and treatment of glomerulonephritis-an update.
AB  - This review updates current concepts of the genetic risk factors, etiologic
      events, nephtitogenic responses and treatment of the major immunologically
      mediated types of glomerulonephritis (GN). These include post-infectious GN, IgA
      nephropathy, anti-glomerular basement membrane (GBM) antibody disease, ANCA
      associated vasculitis (AAV) and lupus nephritis. Although the etiology(s) of most
      GNs remain undefined, many are now believed to be initiated by environmental
      insults, particularly infectious processes, that trigger host responses in
      genetically susceptible individuals which lead to GN. Mechanistic concepts of
      these diseases have evolved from earlier views that most were consequent to
      glomerular trapping of preformed immune complexes to the current view that most
      of these diseases are auto-immune in nature mediated by both antibodies and T
      cells reactive with self-antigens. Therapy of GN has lagged behind advances in
      understanding pathogenesis. Newly appreciated roles for older mediators like
      complement and complement regulatory proteins offer new therapeutic targets. 

PMID- 27049373
TI  - Renal hydatid cyst: medical treatment.
AB  - INTRODUCTION: Hydatid disease is a zoonosis caused by the parasite Echinococcus
      granulosus. It has a worldwide distribution, being endemic in Portugal. Hydatid
      disease of the urinary tract is rare, occurring in less than 2% of all cases.
      CASE REPORT: 14-year-old male with hydatid disease of the kidney. The diagnosis
      was established by imaging studies and specific serologic testing. Treatment
      consisted of four 4-week cycles of albendazol and resulted in a progressive
      reduction of the cyst as well as in a negative specific serology. DISCUSSION:
      Even though the recommended treatment is surgical excision, studies have
      demonstrated that medical treatment may be an alternative allowing for organ
      preservation.

PMID- 27049374
TI  - A case of Chagas' disease panniculitis after kidney transplantation.
AB  - Chagas' disease carries high morbidity and mortality due to acute parasitemia or
      cardiac, digestive, cutaneous or neurologic chronic lesions. Latin American
      countries have the majority of infected or at risk people. Transplanted patients
      using immunosuppressive agents may develop severe and even fatal forms of the
      disease. The available treatment causes frequent severe side-effects. A 59 years
      old woman with end stage renal disease and positive serology for Chagas' disease,
      but without any clinical manifestation of this pathology, underwent kidney
      transplantation from a cadaveric donor and displayed three months later a thigh
      panniculitis from which a biopsy unveiled amastigote forms of Trypanosoma cruzi.
      The skin lesions disappeared following treatment with benzonidazole, but the drug
      was discontinued due to severe pancytopenia. Along with this, infection with E.
      faecalis and cytomegalovirus were treated with vancomicin and ganciclovir. The
      patient kept very well afterwards, with no new skin lesions and with good graft
      function. One year and three months after the transplant, she had an emergency
      surgery for an aortic dissecting aneurysm. Irreversible shock and death occurred
      in the immediate post-surgical period. It was not possible to establish or to
      rule out a relationship between the trypanosomiasis and the aortic lesions.
      Chagas' disease must be remembered in differential diagnosis of several clinical
      situations in transplant patients, mainly in endemic areas. The treatment can
      yeld good clinical response, but serious side-effects from the drugs may ensue.
      More effective and better tolerated options are in need for treatment or
      prophylaxis. 

PMID- 27049375
TI  - TINU syndrome: review of the literature and case report.
AB  - INTRODUCTION: Tubulointerstitial nephritis and uveitis syndrome (TINU Syndrome)
      is an uncommon clinical entity, and the majority of patients are adolescents and
      young women. The case reported refers to an elderly patient with ophthalmologic
      symptoms detected earlier than kidney manifestations, being probably the first
      case described in Brazil. CASE REPORT: Female patient, 60 years-old, sought
      medical attention for complaints of "red eye". Three months after the first
      episode of eye manifestation, the patient presented with systemic symptoms and
      renal dysfunction. Renal biopsy showed tubulointerstitial nephritis with signs of
      activity. DISCUSSION: The pathophysiology of TINU Syndrome remains poorly
      understood, probably involving both cellular and humoral immunity. This syndrome
      can be differentiated from systemic conditions associated with nephritis and
      uveitis, and prior exclusion of other diseases is necessary to confirm diagnosis,
      especially in the presence of ophthalmologic findings. CONCLUSION: The clinical
      suspicion and the knowledge of the management of the disease by nephrologists,
      internists and ophthalmologists is mandatory in the treatment of patients with
      TINU Syndrome.

PMID- 27049376
TI  - A case of renal recovery in atypical hemolytic uremic syndrome treated with
      eculizumab.
AB  - Atypical Hemolytic Uremic Syndrome (aHUS) is a rare, life-threatening disease
      that can occur at any age and be sporadic or familial. aHUS is caused by an
      uncontrolled activation of the complement system. Plasma Exchange (PE) has been
      the standard treatment for years with poor results, leading approximately 40% of
      patients to end-stage renal disease (ESRD) or death during the first clinical
      manifestation. Eculizumab, an humanized monoclonal antibody directed against
      complement component C5, has emerged in the last few years as a new therapheutic
      aproach with promising results. Our goal is to present a case of an adult patient
      where eculizumab was sucessfully used as upfront therapy avoiding the potential
      significant morbidity of PE. 

PMID- 27049377
TI  - Synthesis of Dense and Chiral Dendritic Polyols Using Glyconanosynthon Scaffolds.
AB  - Most classical dendrimers are frequently built-up from identical repeating units
      of low valency (usually AB2 monomers). This strategy necessitates several
      generations to achieve a large number of surface functionalities. In addition,
      these typical monomers are achiral. We propose herein the use of sugar
      derivatives consisting of several and varied functionalities with their own
      individual intrinsic chirality as both scaffolds/core as well as repeating units.
      This approach allows the construction of chiral, dense dendrimers with a large
      number of surface groups at low dendrimer generations. Perpropargylated beta-D
      glucopyranoside, serving as an A5 core, together with various derivatives, such
      as 2-azidoethyl tetra-O-allyl-beta-D-glucopyranoside, serving as an AB4 repeating
      moiety, were utilized to construct chiral dendrimers using "click chemistry"
      (CuAAC reaction). These were further modified by thiol-ene and thiol-yne click
      reactions with alcohols to provide dendritic polyols. Molecular dynamic
      simulation supported the assumption that the resulting polyols have a dense
      structure. 

PMID- 27049378
TI  - Anti-Inflammatory Effect of Quercetin on RAW 264.7 Mouse Macrophages Induced with
      Polyinosinic-Polycytidylic Acid.
AB  - Quercetin (3,3',4',5,6-pentahydroxyflavone) is a well-known antioxidant and a
      flavonol found in many fruits, leaves, and vegetables. Quercetin also has known
      anti-inflammatory effects on lipopolysaccharide-induced macrophages. However, the
      effects of quercetin on virus-induced macrophages have not been fully reported.
      In this study, the anti-inflammatory effect of quercetin on double-stranded RNA
      (dsRNA)-induced macrophages was examined. Quercetin at concentrations up to 50
      MUM significantly inhibited the production of NO, IL-6, MCP-1, IP-10, RANTES, GM
      CSF, G-CSF, TNF-alpha, LIF, LIX, and VEGF as well as calcium release in dsRNA (50
      MUg/mL of polyinosinic-polycytidylic acid)-induced RAW 264.7 mouse macrophages (p
      < 0.05). Quercetin at concentrations up to 50 MUM also significantly inhibited
      mRNA expression of signal transducer and activated transcription 1 (STAT1) and
      STAT3 in dsRNA-induced RAW 264.7 cells (p < 0.05). In conclusion, quercetin had
      alleviating effects on viral inflammation based on inhibition of NO, cytokines,
      chemokines, and growth factors in dsRNA-induced macrophages via the calcium-STAT
      pathway. 

PMID- 27049379
TI  - Effects of Phenolic Acids on the Growth and Production of T-2 and HT-2 Toxins by
      Fusarium langsethiae and F. sporotrichioides.
AB  - The effect of natural phenolic acids was tested on the growth and production of T
      2 and HT-2 toxins by Fusarium langsethiae and F. sporotrichioides, on Mycotoxin
      Synthetic medium. Plates treated with 0.5 mM of each phenolic acid (caffeic,
      chlorogenic, ferulic and p-coumaric) and controls without phenolic acid were
      incubated for 14 days at 25  degrees C. Fungal biomass of F. langsethiae and F.
      sporotrichioides was not reduced by the phenolic acids. However, biosynthesis of
      T-2 toxin by F. langsethiae was significantly reduced by chlorogenic (23.1%) and
      ferulic (26.5%) acids. Production of T-2 by F. sporotrichioides also decreased
      with ferulic acid by 23% (p < 0.05). In contrast, p-coumaric acid significantly
      stimulated the production of T-2 and HT-2 toxins for both strains. A kinetic
      study of F. langsethiae with 1 mM ferulic acid showed a significant decrease in
      fungal biomass, whereas T-2 production increased after 10 days of incubation. The
      study of gene expression in ferulic supplemented cultures of F. langsethiae
      revealed a significant inhibition for Tri5, Tri6 and Tri12 genes, while for Tri16
      the decrease in gene expression was not statistically significant. Overall,
      results indicated that phenolic acids had a variable effect on fungal growth and
      mycotoxin production, depending on the strain and the concentration and type of
      phenolic acid assayed. 

PMID- 27049380
TI  - Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.
AB  - Liver transplant is the unique curative therapy for patients with acute liver
      failure or end-stage liver disease, with or without hepatocellular carcinoma.
      Increase of body weight, onset of insulin resistance and drug-induced alterations
      of metabolism are reported in liver transplant recipients. In this context, post
      transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be
      often diagnosed. Multifactorial illnesses occurring in the post-transplant period
      represent significant causes of morbidity and mortality. This is especially true
      for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic
      manifestations of metabolic syndrome and after liver transplant both recurrent
      and de novo steatosis can be found. Usually, post-transplant steatosis shows an
      indolent outcome with few cases of fibrosis progression. However, in the post
      transplant setting, both metabolic syndrome and steatosis might play a key role
      in the stratification of morbidity and mortality risk, being commonly associated
      with cardiovascular disease. The single components of metabolic syndrome can be
      treated with targeted drugs while lifestyle intervention is the only reasonable
      therapeutic approach for transplant patients with non-alcoholic steatosis or
      steatohepatitis. 

PMID- 27049381
TI  - Bacterial Expression and Kinetic Analysis of Carboxylesterase 001D from
      Helicoverpa armigera.
AB  - Carboxylesterasesare an important class of detoxification enzymes involved in
      insecticide resistance in insects. A subgroup of Helicoverpa armigera esterases,
      known as Clade 001, was implicated in organophosphate and pyrethroid insecticide
      resistance due to their overabundance in resistant strains. In this work, a novel
      carboxylesterasegene 001D of H. armigera from China was cloned, which has an open
      reading frame of 1665 nucleotides encoding 554 amino acid residues. We used a
      series of fusion proteins to successfully express carboxylesterase 001D in
      Escherichia coli. Three different fusion proteins were generated and tested. The
      enzyme kinetic assay towards 1-naphthyl acetate showed all three purified fusion
      proteins are active with a Kcat between 0.35 and 2.29 s(-1), and a Km between
      7.61 and 19.72 MUM. The HPLC assay showed all three purified fusion proteins had
      low but measurable hydrolase activity towards beta-cypermethrin and fenvalerate
      insecticides (specific activities ranging from 0.13 to 0.67 MUM.min(-1).(MUM(
      1).protein)). The enzyme was stable up to 40  degrees C and at pH 6.0-11.0. The
      results imply that carboxylesterase 001D is involved in detoxification, and this
      moderate insecticide hydrolysis may suggest that overexpression of the gene to
      enhance insecticide sequestration is necessary to allow carboxylesterases to
      confer resistance to these insecticides in H. armigera. 

PMID- 27049382
TI  - Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell
      Proliferation.
AB  - Most studies of Wnt signaling in malignant tissues have focused on the canonical
      Wnt pathway (CWP) due to its role in stimulating cellular proliferation. The role
      of the non-canonical Wnt pathway (NCWP) in tissues with dysregulated Wnt
      signaling is not fully understood. Understanding NCWP's role is important since
      these opposing pathways act in concert to maintain homeostasis in healthy
      tissues. Our preliminary studies demonstrated that LiCl inhibited proliferation
      of primary cells derived from colorectal cancer (CRC). Since LiCl stimulates cell
      proliferation in normal tissues and NCWP suppresses it, the present study was
      designed to investigate the impact of NCWP components in LiCl-mediated effects.
      LiCl-mediated inhibition of CRC cell proliferation (p < 0.001) and increased
      apoptosis (p < 0.01) coincided with 23-fold increase (p < 0.025) in the
      expression of the NCWP ligand, Wnt9A. LiCl also suppressed beta-catenin mRNA (p <
      0.03), total beta-catenin protein (p < 0.025) and the active form of beta
      catenin. LiCl-mediated inhibition of CRC cell proliferation was partially
      reversed by IWP-2, and Wnt9A antibody. Recombinant Wnt9A protein emulated LiCl
      effects by suppressing beta-catenin protein (p < 0.001), inhibiting proliferation
      (p < 0.001) and increasing apoptosis (p < 0.03). This is the first study to
      demonstrate induction of a NCWP ligand, Wnt9A as part of a mechanism for LiCl
      mediated suppression of CRC cell proliferation. 

PMID- 27049385
TI  - Design and Vibration Sensitivity Analysis of a MEMS Tuning Fork Gyroscope with an
      Anchored Diamond Coupling Mechanism.
AB  - In this paper, a new micromachined tuning fork gyroscope (TFG) with an anchored
      diamond coupling mechanism is proposed while the mode ordering and the vibration
      sensitivity are also investigated. The sense-mode of the proposed TFG was
      optimized through use of an anchored diamond coupling spring, which enables the
      in-phase mode frequency to be 108.3% higher than the anti-phase one. The
      frequencies of the in- and anti-phase modes in the sense direction are 9799.6 Hz
      and 4705.3 Hz, respectively. The analytical solutions illustrate that the
      stiffness difference ratio of the in- and anti-phase modes is inversely
      proportional to the output induced by the vibration from the sense direction.
      Additionally, FEM simulations demonstrate that the stiffness difference ratio of
      the anchored diamond coupling TFG is 16.08 times larger than the direct coupling
      one while the vibration output is reduced by 94.1%. Consequently, the proposed
      new anchored diamond coupling TFG can structurally increase the stiffness
      difference ratio to improve the mode ordering and considerably reduce the
      vibration sensitivity without sacrificing the scale factor. 

PMID- 27049384
TI  - Triptolide Modulates TREM-1 Signal Pathway to Inhibit the Inflammatory Response
      in Rheumatoid Arthritis.
AB  - Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F,
      has therapeutic potential against rheumatoid arthritis (RA). However, the
      underlying molecular mechanism has not been fully elucidated. The aim of this
      study is to investigate the mechanisms of TP acting on RA by combining
      bioinformatics analysis with experiment validation. The human protein targets of
      TP and the human genes of RA were found in the PubChem database and NCBI,
      respectively. These two dataset were then imported into Ingenuity Pathway
      Analysis (IPA) software online, and then the molecular network of TP on RA could
      be set up and analyzed. After that, both in vitro and in vivo experiments were
      done to further verify the prediction. The results indicated that the main
      canonical signal pathways of TP protein targets networks were mainly centered on
      cytokine and cellular immune signaling, and triggering receptors expressed on
      myeloid cells (TREM)-1 signaling was searched to be the top one shared signaling
      pathway and involved in the cytokine and cellular immune signaling. Further in
      vitro experiments indicated that TP not only remarkably lowered the levels of
      TREM-1 and DNAX-associated protein (DAP)12, but also significantly suppressed the
      activation of janus activating kinase (JAK)2 and signal transducers and
      activators of transcription (STAT)3. The expression of tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta and IL-6 in lipopolysaccharides (LPS)
      stimulated U937 cells also decreased after treatment with TP. Furthermore, TREM-1
      knockdown was able to interfere with the inhibition effects of TP on these
      cytokines production. In vivo experiments showed that TP not only significantly
      inhibited the TREM-1 mRNA and DAP12 mRNA expression, and activation of JAK2 and
      STAT3 in ankle of rats with collagen-induced arthritis (CIA), but also remarkably
      decreased production of TNF-alpha, IL-1beta and IL-6 in serum and joint. These
      findings demonstrated that TP could modulate the TREM1 signal pathway to inhibit
      the inflammatory response in RA. 

PMID- 27049386
TI  - A Novel Field-Circuit FEM Modeling and Channel Gain Estimation for Galvanic
      Coupling Real IBC Measurements.
AB  - Existing research on human channel modeling of galvanic coupling intra-body
      communication (IBC) is primarily focused on the human body itself. Although
      galvanic coupling IBC is less disturbed by external influences during signal
      transmission, there are inevitable factors in real measurement scenarios such as
      the parasitic impedance of electrodes, impedance matching of the transceiver,
      etc. which might lead to deviations between the human model and the in vivo
      measurements. This paper proposes a field-circuit finite element method (FEM)
      model of galvanic coupling IBC in a real measurement environment to estimate the
      human channel gain. First an anisotropic concentric cylinder model of the
      electric field intra-body communication for human limbs was developed based on
      the galvanic method. Then the electric field model was combined with several
      impedance elements, which were equivalent in terms of parasitic impedance of the
      electrodes, input and output impedance of the transceiver, establishing a field
      circuit FEM model. The results indicated that a circuit module equivalent to
      external factors can be added to the field-circuit model, which makes this model
      more complete, and the estimations based on the proposed field-circuit are in
      better agreement with the corresponding measurement results. 

PMID- 27049383
TI  - Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes
      including vasospasm, cognitive decline, and even death. Currently, treatment
      options are limited for this potentially life threatening injury. Recent evidence
      suggests that neuroinflammation plays a critical role in injury expansion and
      brain damage. Red blood cell breakdown products can lead to the release of
      inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical
      models have been used successfully to improve understanding about
      neuroinflammation following aneurysmal rupture. The focus of this review is to
      provide an overview of how neuroinflammation relates to secondary outcomes such
      as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical
      agents that warrant further investigation for the treatment of subarachnoid
      hemorrhage. We provide a concise overview of the neuroinflammatory pathways that
      are upregulated following aneurysmal rupture and how these pathways correlate to
      long-term outcomes. Treatment of aneurysm rupture is limited and few
      pharmaceutical drugs are available. Through improved understanding of biochemical
      mechanisms of injury, novel treatment solutions are being developed that target
      neuroinflammation. In the final sections of this review, we highlight a few of
      these novel treatment approaches and emphasize why targeting neuroinflammation
      following aneurysmal subarachnoid hemorrhage may improve patient care. We
      encourage ongoing research into the pathophysiology of aneurysmal subarachnoid
      hemorrhage, especially in regards to neuroinflammatory cascades and the
      translation to randomized clinical trials. 

PMID- 27049387
TI  - MapSentinel: Can the Knowledge of Space Use Improve Indoor Tracking Further?
AB  - Estimating an occupant's location is arguably the most fundamental sensing task
      in smart buildings. The applications for fine-grained, responsive building
      operations require the location sensing systems to provide location estimates in
      real time, also known as indoor tracking. Existing indoor tracking systems
      require occupants to carry specialized devices or install programs on their
      smartphone to collect inertial sensing data. In this paper, we propose
      MapSentinel, which performs non-intrusive location sensing based on WiFi access
      points and ultrasonic sensors. MapSentinel combines the noisy sensor readings
      with the floormap information to estimate locations. One key observation
      supporting our work is that occupants exhibit distinctive motion characteristics
      at different locations on the floormap, e.g., constrained motion along the
      corridor or in the cubicle zones, and free movement in the open space. While
      extensive research has been performed on using a floormap as a tool to obtain
      correct walking trajectories without wall-crossings, there have been few attempts
      to incorporate the knowledge of space use available from the floormap into the
      location estimation. This paper argues that the knowledge of space use as an
      additional information source presents new opportunities for indoor tracking. The
      fusion of heterogeneous information is theoretically formulated within the Factor
      Graph framework, and the Context-Augmented Particle Filtering algorithm is
      developed to efficiently solve real-time walking trajectories. Our evaluation in
      a large office space shows that the MapSentinel can achieve accuracy improvement
      of 31.3% compared with the purely WiFi-based tracking system.

PMID- 27049388
TI  - Automatic Identification of Subtechniques in Skating-Style Roller Skiing Using
      Inertial Sensors.
AB  - This study aims to develop and validate an automated system for identifying
      skating-style cross-country subtechniques using inertial sensors. In the first
      experiment, the performance of a male cross-country skier was used to develop an
      automated identification system. In the second, eight male and seven female
      college cross-country skiers participated to validate the developed
      identification system. Each subject wore inertial sensors on both wrists and both
      roller skis, and a small video camera on a backpack. All subjects skied through a
      3450 m roller ski course using a skating style at their maximum speed. The
      adopted subtechniques were identified by the automated method based on the data
      obtained from the sensors, as well as by visual observations from a video
      recording of the same ski run. The system correctly identified 6418 subtechniques
      from a total of 6768 cycles, which indicates an accuracy of 94.8%. The precisions
      of the automatic system for identifying the V1R, V1L, V2R, V2L, V2AR, and V2AL
      subtechniques were 87.6%, 87.0%, 97.5%, 97.8%, 92.1%, and 92.0%, respectively.
      Most incorrect identification cases occurred during a subtechnique identification
      that included a transition and turn event. Identification accuracy can be
      improved by separately identifying transition and turn events. This system could
      be used to evaluate each skier's subtechniques in course conditions. 

PMID- 27049389
TI  - Towards Real-Time Detection of Freezing of Gait Using Wavelet Transform on
      Wireless Accelerometer Data.
AB  - Injuries associated with fall incidences continue to pose a significant burden to
      persons with Parkinson's disease (PD) both in terms of human suffering and
      economic loss. Freezing of gait (FOG), which is one of the symptoms of PD, is a
      common cause of falls in this population. Although a significant amount of work
      has been performed to characterize/detect FOG using both qualitative and
      quantitative methods, there remains paucity of data regarding real-time detection
      of FOG, such as the requirements for minimum sensor nodes, sensor placement
      locations, and appropriate sampling period and update time. Here, the continuous
      wavelet transform (CWT) is employed to define an index for correctly identifying
      FOG. Since the CWT method uses both time and frequency components of a waveform
      in comparison to other methods utilizing only the frequency component, we
      hypothesized that using this method could lead to a significant improvement in
      the accuracy of FOG detection. We tested the proposed index on the data of 10 PD
      patients who experience FOG. Two hundred and thirty seven (237) FOG events were
      identified by the physiotherapists. The results show that the index could
      discriminate FOG in the anterior-posterior axis better than other two axes, and
      is robust to the update time variability. These results suggest that real time
      detection of FOG may be realized by using CWT of a single shank sensor with
      window size of 2 s and update time of 1 s (82.1% and 77.1% for the sensitivity
      and specificity, respectively). Although implicated, future studies should
      examine the utility of this method in real-time detection of FOG. 

PMID- 27049390
TI  - A Portable Low-Power Acquisition System with a Urease Bioelectrochemical Sensor
      for Potentiometric Detection of Urea Concentrations.
AB  - This paper presents a portable low-power battery-driven bioelectrochemical signal
      acquisition system for urea detection. The proposed design has several
      advantages, including high performance, low cost, low-power consumption, and high
      portability. A LT1789-1 low-supply-voltage instrumentation amplifier (IA) was
      used to measure and amplify the open-circuit potential (OCP) between the working
      and reference electrodes. An MSP430 micro-controller was programmed to process
      and transduce the signals to the custom-developed software by ZigBee RF module in
      wireless mode and UART in able mode. The immobilized urease sensor was prepared
      by embedding urease into the polymer (aniline-co-o-phenylenediamine) polymeric
      matrix and then coating/depositing it onto a MEMS-fabricated Au working
      electrode. The linear correlation established between the urea concentration and
      the potentiometric change is in the urea concentrations range of 3.16 * 10(-4) to
      3.16 * 10(-2) M with a sensitivity of 31.12 mV/log [M] and a precision of 0.995
      (R2 = 0.995). This portable device not only detects urea concentrations, but can
      also operate continuously with a 3.7 V rechargeab-le lithium-ion battery (500
      mA.h) for at least four days. Accordingly, its use is feasible and even promising
      for home-care applications. 

PMID- 27049391
TI  - Evaluation of Smartphone Inertial Sensor Performance for Cross-Platform Mobile
      Applications.
AB  - Smartphone sensors are being increasingly used in mobile applications. The
      performance of sensors varies considerably among different smartphone models and
      the development of a cross-platform mobile application might be a very complex
      and demanding task. A publicly accessible resource containing real-life-situation
      smartphone sensor parameters could be of great help for cross-platform
      developers. To address this issue we have designed and implemented a pilot
      participatory sensing application for measuring, gathering, and analyzing
      smartphone sensor parameters. We start with smartphone accelerometer and
      gyroscope bias and noise parameters. The application database presently includes
      sensor parameters of more than 60 different smartphone models of different
      platforms. It is a modest, but important start, offering information on several
      statistical parameters of the measured smartphone sensors and insights into their
      performance. The next step, a large-scale cloud-based version of the application,
      is already planned. The large database of smartphone sensor parameters may prove
      particularly useful for cross-platform developers. It may also be interesting for
      individual participants who would be able to check-up and compare their
      smartphone sensors against a large number of similar or identical models. 

PMID- 27049392
TI  - Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a
      Chip Applications.
AB  - THz spectroscopy is an emerging technique for studying the dynamics and
      interactions of cells and biomolecules, but many practical challenges still
      remain in experimental studies. We present a prototype of simple and inexpensive
      cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells
      are transported, trapped and concentrated into the THz exposure region by
      applying an AC bias signal while the chip maintains a steady temperature at 37 
      degrees C by resistive heating. We conduct some preliminary experiments on E.
      coli and T-cell solution and compare the transmission spectra of empty channels,
      channels filled with aqueous media only, and channels filled with aqueous media
      with un-concentrated and concentrated cells. 

PMID- 27049393
TI  - New Cyclic Lipopeptides of the Iturin Class Produced by Saltern-Derived Bacillus
      sp. KCB14S006.
AB  - Salterns, one of the most extreme natural hypersaline environments, are a rich
      source of halophilic and halotolerant microorganisms, but they remain largely
      underexplored ecological niches in the discovery of bioactive secondary
      metabolites. In continued efforts to investigate the metabolic potential of
      microbial populations from chemically underexplored sites, three new lipopeptides
      named iturin F1, iturin F2 and iturin A9 (1-3), along with iturin A8 (4), were
      isolated from Bacillus sp. KCB14S006 derived from a saltern. The structures of
      the isolated compounds were established by 1D-, 2D-NMR and HR-ESIMS, and their
      absolute configurations were determined by applying advanced Marfey's method and
      CD spectroscopy. All isolates exhibited significant antifungal activities against
      various pathogenic fungi and moderate cytotoxic activities toward HeLa and
      src(ts)-NRK cell lines. Moreover, in an in vitro enzymatic assay, compound 4
      showed a significant inhibitory activity against indoleamine 2,3-dioxygenase. 

PMID- 27049395
TI  - The Haze Nightmare Following the Economic Boom in China: Dilemma and Tradeoffs.
AB  - This study aims to expand on a deeper understanding of the relationship between
      rapid economic development and ensuing air pollution in China. The database
      includes the gross domestic product (GDP), the value added of a secondary
      industry, the per capita GDP (PGDP), greenhouse gases emissions, and PM2.5
      concentrations. The results indicate that China's PGDP has continued to rise over
      the past decade, and the rate of PGDP slowed down from 1980 to 2004 (slope =
      5672.81, R2 = 0.99, p < 0.001) but was significantly lower than that from the
      year 2004 to 2013 (slope = 46,911.08, R2 > 0.99, p < 0.001). Unfortunately, we
      found that total coal consumption, annual steel production, and SO2 emission had
      been continually growing as the overall economy expands at temporal scale, with
      the coefficient of determinations greater than 0.98 (p < 0.001). Considering the
      spatial pattern aspect, we also found a significant relationship between GDP and
      greenhouse gases. Meanwhile, severe air pollution has negatively impacted the
      environment and human health, particularly in some highlighted regions. The
      variation explained by both total SO2 emission and total smoke and dust emission
      were 33% (p < 0.001) and 24% (p < 0.01) for the rate of total pertussis at
      temporal scale, respectively. Furthermore, at the spatial scale, pulmonary
      tuberculosis rates and pertussis mainly occurred in area with serious air
      pollution (economically developed region). It can be summarized that the
      extensive mode of economic growth has brought a number of serious environment and
      human health problems. Thus, a new policy framework has been proposed to meet the
      goals of maintaining a healthy economy without harming natural environment, which
      may prove integral, especially when coupled with long-term national strategic
      development plans. 

PMID- 27049394
TI  - Adaptation and Evaluation of the Neighborhood Environment Walkability Scale in
      India (NEWS-India).
AB  - Physical inactivity is the fourth leading risk factor for global mortality, with
      most of these deaths occurring in low and middle-income countries (LMICs) like
      India. Research from developed countries has consistently demonstrated
      associations between built environment features and physical activity levels of
      populations. The development of culturally sensitive and reliable measures of the
      built environment is a necessary first step for accurate analysis of
      environmental correlates of physical activity in LMICs. This study systematically
      adapted the Neighborhood Environment Walkability Scale (NEWS) for India and
      evaluated aspects of test-retest reliability of the adapted version among Indian
      adults. Cultural adaptation of the NEWS was conducted by Indian and international
      experts. Semi-structured interviews were conducted with local residents and key
      informants in the city of Chennai, India. At baseline, participants (N = 370;
      female = 47.2%) from Chennai completed the adapted NEWS-India surveys on
      perceived residential density, land use mix-diversity, land use mix-access,
      street connectivity, infrastructure and safety for walking and cycling,
      aesthetics, traffic safety, and safety from crime. NEWS-India was administered
      for a second time to consenting participants (N = 62; female = 53.2%) with a gap
      of 2-3 weeks between successive administrations. Qualitative findings
      demonstrated that built environment barriers and constraints to active commuting
      and physical activity behaviors intersected with social ecological systems. The
      adapted NEWS subscales had moderate to high test-retest reliability (ICC range
      0.48-0.99). The NEWS-India demonstrated acceptable measurement properties among
      Indian adults and may be a useful tool for evaluation of built environment
      attributes in India. Further adaptation and evaluation in rural and suburban
      settings in India is essential to create a version that could be used throughout
      India. 

PMID- 27049396
TI  - Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct
      Effects of Fructose on Adipocyte Precursor Cells.
AB  - We have previously addressed that fructose rich diet (FRD) intake for three weeks
      increases the adipogenic potential of stromal vascular fraction cells from the
      retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of
      prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte
      precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and
      FRD adult male rats. Additionally, we have examined the direct fructose effects
      on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma
      levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size.
      FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads;
      data is supported by high mRNA levels of competency markers: PPARgamma2 and
      Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal
      APCs displayed an overall increased adipogenic capacity. We conclude that the
      RPAT mass expansion observed in eight week-FRD fed rats depends on combined
      accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct
      effect of fructose on APCs. 

PMID- 27049398
TI  - Reproduction and Population Dynamics as Biotypic Markers of Russian Wheat Aphid
      Diuraphis noxia (Kurdjumov).
AB  - Russian wheat aphid Diuraphis noxia (Kurdjumov) is widely established in wheat
      growing countries where it causes significant economic losses. The development
      and use of Russian wheat aphid (RWA)-resistant wheat varieties has been
      constrained by the variation in resident RWA populations and the evolution of
      virulent biotypes. An experiment was set up at the Kenya Agricultural and
      Livestock Research Organization (KALRO), Njoro, to characterize RWA populations
      based on phenotypic characteristics of reproduction, development and population
      dynamics. RWA populations from the regions of Eldoret, Mau Narok and Njoro were
      used in the study. A factorial experiment was set up in randomized complete block
      design replicated eleven times. A single day-old nymph was placed on a new, fully
      open leaf in a 0.5 cm-diameter clear plastic straw leaf cage and observed daily
      for its entire lifetime. The results showed that there were variations in aphid
      lifespan, reproductive longevity and aphid fecundity between populations,
      indicating that the phenotypic markers used to determine biotypes were good
      enough to show distinct biotypes among populations of the RWA in Kenya. Further,
      the study concluded that the use of phenotypic life and reproductive markers was
      a valid way of characterizing biotypes of RWA worldwide. 

PMID- 27049397
TI  - Bioinformatics Analysis of MAPKKK Family Genes in Medicago truncatula.
AB  - Mitogen-activated protein kinase kinase kinase (MAPKKK) is a component of the
      MAPK cascade pathway that plays an important role in plant growth, development,
      and response to abiotic stress, the functions of which have been well
      characterized in several plant species, such as Arabidopsis, rice, and maize. In
      this study, we performed genome-wide and systemic bioinformatics analysis of
      MAPKKK family genes in Medicago truncatula. In total, there were 73 MAPKKK family
      members identified by search of homologs, and they were classified into three
      subfamilies, MEKK, ZIK, and RAF. Based on the genomic duplication function, 72
      MtMAPKKK genes were located throughout all chromosomes, but they cluster in
      different chromosomes. Using microarray data and high-throughput sequencing-data,
      we assessed their expression profiles in growth and development processes; these
      results provided evidence for exploring their important functions in
      developmental regulation, especially in the nodulation process. Furthermore, we
      investigated their expression in abiotic stresses by RNA-seq, which confirmed
      their critical roles in signal transduction and regulation processes under
      stress. In summary, our genome-wide, systemic characterization and expressional
      analysis of MtMAPKKK genes will provide insights that will be useful for
      characterizing the molecular functions of these genes in M. truncatula. 

PMID- 27049399
TI  - Aqueous Extracts from Tunisian Diplotaxis: Phenol Content, Antioxidant and Anti
      Acetylcholinesterase Activities, and Impact of Exposure to Simulated
      Gastrointestinal Fluids.
AB  - Antioxidants have been considered essential for preventing cell damage by
      scavenging deleterious free radicals. The consumption of antioxidant-rich plants
      is associated with a reduced risk of some chronic diseases. This study evaluates
      the antioxidant and acetylcholinesterase inhibition activities of aqueous
      extracts obtained from different parts of Diplotaxis simplex and Diplotaxis harra
      from Tunisia. The study also aimed to investigate the action of simulated
      gastrointestinal juice on antioxidant activities of both extracts. The total
      phenolic, flavone and flavonol, and flavanone and dihydroflavonol contents were
      determined by Folin-Ciocalteau, aluminum chloride and 2,4-dinitrophenylhydrazine
      colorimetric methods, respectively. The metal ion chelating activity,
      acetylcholinesterase inhibition capacity, and free radical scavenging potential
      of the extracts towards ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic
      acid), DPPH (2,2-diphenyl-1-picrylhydrazyl), hydroxyl, superoxide and nitric
      oxide were also evaluated. The action of simulated gastro-intestinal fluids on
      the flavone and flavonol content and total antioxidant activity of the flower
      extracts was surveyed. Extracts from the seeds and flowers of D. simplex and D.
      harra displayed the highest amounts of phenols (2691.7 and 2694.5 mg Caffeic Acid
      Equivalent (CAE)/100 mg; 3433.4 and 2647.2 mg CAE/100 mg, respectively) and
      flavonols/flavones (2144.4 and 2061.1 mg Rutin Equivalent (RE)/100 g; 1922.6 and
      1461.1 mg RE/100 g, respectively). The flower and seed extracts exhibited the
      highest rates of antioxidant and acetylcholinesterase inhibition activities. A
      decrease in the flavonoid content and antioxidant activity was observed after
      extract exposure to simulated saliva. Antioxidant and acetylcholinesterase
      inhibition activities were noted to depend on plant species and plant parts. In
      vitro gastrointestinal digestion is useful in assessing the bio-accessibility of
      compounds with biological activities from food. The simulated gastrointestinal
      fluids influenced the flavonoid concentration and antioxidant activity. 

PMID- 27049400
TI  - Healing livers, saving lives: Hepatitis C screening in an era of cure.
AB  - Chronic hepatitis C affects more than 3 million people in the United States. In
      the past, drug therapy with interferon and ribavirin resulted in low overall cure
      rates and early discontinuation due to adverse reactions. The new direct-acting
      antivirals offer not only a shorter duration of treatment with fewer adverse
      reactions, but greatly improved overall cure rates as high as 96%. Updated
      national screening recommendations (including a one-time screening for patients
      born between 1945 and 1965), combined with timely referral and treatment, offer a
      prime opportunity for healthcare providers to improve public health outcomes and
      reduce healthcare costs. 

PMID- 27049401
TI  - Recognizing, diagnosing, and treating rhabdomyolysis.
AB  - Rhabdomyolysis is an acute and potentially fatal syndrome characterized by
      striated muscle breakdown and subsequent release of muscle cell contents into the
      systemic circulation. The sudden release of large quantities of potassium,
      calcium, organic acids, and myoglobin into the bloodstream can cause renal tubal
      toxicity, cardiac dysrhythmias, and death. Complications can be managed and
      minimized if predicted and treated early, but patients may not have classic
      symptoms of rhabdomyolysis and may even be asymptomatic on presentation. This
      article reviews the pathophysiology, causes, diagnosis, and treatment of acute
      rhabdomyolysis. 

PMID- 27049402
TI  - The impact of concomitant fibromyalgia on visual analogue scales of pain, fatigue
      and function in patients with various rheumatic disorders.
AB  - OBJECTIVES: To evaluate the impact of concomitant fibromyalgia on the rating of
      pain, fatigue, and dysfunction, in patients with various rheumatic disorders.
      METHODS: A cross-sectional study was carried out in a hospital-based rheumatology
      unit. Standard clinical and laboratory data were obtained and all patients
      completed questionnaires on pain, fatigue, and daily function. The rate of
      concomitant fibromyalgia was estimated using the 1990 American College of
      Rheumatology (ACR) classification criteria for fibromyalgia and the analysis
      concentrated on visual analogue scales (VAS). RESULTS: Six hundred and eighteen
      visits of 383 patients with inflammatory as well as non-inflammatory rheumatic
      disorders were analyzed. Concomitant fibromyalgia was noted in 74 patients (23%
      of the cohort). Patients with rheumatic diseases and concomitant fibromyalgia had
      significantly higher mean VAS scores for pain, fatigue, and function (79+/-17,
      81+/-18, 80+/-18, respectively) as compared to patients who had no features of
      fibromyalgia (47+/-28, 50+/-29, 44+/-30 respectively; all p values <0.001). The
      scores reported by patients with rheumatic diseases and concomitant fibromyalgia
      were similar to the scores obtained from patients with primary FM. CONCLUSIONS:
      Concomitant FM is common both among patients with inflammatory and patients with
      non inflammatory rheumatic disorders. Concomitant FM has a remarkable impact on
      the severity of symptoms and, moreover, patients with concomitant FM exhibit
      extreme and significantly distinct levels of pain and fatigue which is as severe
      as that reported by patients with primary FM. It seems that fibromyalgic features
      dominate and become the main cause of morbidity in rheumatological patients with
      concomitant FM.

PMID- 27049403
TI  - Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like
      Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.
AB  - Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on
      the functionality of attached ligands. Understanding how the ligands interact
      with the receptors in cell membrane and its further effect on the cellular uptake
      of dendrimer-like soft nanoparticles is thereby a key issue for their better
      application in nanomedicine. However, the essential mechanism and detailed
      kinetics for the ligand-receptor interaction-mediated transmembrane transport of
      such unconventional nanoparticles remain poorly elucidated. Here, using coarse
      grained simulations, we present the very first study of molecular mechanism and
      kinetics behaviors for the transmembrane transport of dendrimer-like soft
      nanoparticles conjugated with ligands. A phase diagram of interaction states is
      constructed through examining ligand densities and membrane tensions that allows
      us to identify novel endocytosis mechanisms featured by the direct wrapping and
      the penetration-extraction vesiculation. The results provide an in-depth insight
      into the diffusivity of receptors and dendrimer in the membrane plane and
      demonstrate how the ligand density influences receptor diffusion and uptake
      kinetics. It is interesting to find that the ligand-conjugated dendrimers present
      superdiffusive behaviors on a membrane, which is revealed to be driven by the
      random fluctuation dynamics of the membrane. The findings facilitate our
      understanding of some recent experimental observations and could establish
      fundamental principles for the future development of such important nanomaterials
      for widespread nanomedical applications.

PMID- 27049408
TI  - Building a Movement to Be the Healthiest Nation.

PMID- 27049404
TI  - Rituximab versus azathioprine for ANCA-associated vasculitis maintenance therapy:
      impact on global disability and health-related quality of life.
AB  - OBJECTIVES: To investigate the effects on health-related quality of life (HRQOL)
      and functional capability of rituximab vs azathioprine for ANCA-associated
      vasculitis (AAV) maintenance therapy. METHODS: In a 24-month phase III randomised
      controlled trial, 115 patients over time received rituximab or azathioprine for
      AAV maintenance therapy. Mean changes of 36-item Short-form Health Survey (SF-36)
      and Health Assessment Questionnaire (HAQ) scores from baseline were analysed.
      RESULTS: Mean improvements of HAQ scores, from baseline to month 24 were
      significantly better for the rituximab (0.16 points lower) than the azathioprine
      group (p=0.038). As demonstrated by SF-36, study patients' baseline HRQOL was
      significantly impaired compared with age- and sex-matched US norms. At month 24,
      mean changes from baseline of SF-36 physical component score tended to be better
      for the rituximab group (+3.95 points, p=0.067) whereas mean changes from
      baseline of the SF-36 mental component score were significantly better for the
      azathioprine group (+4.23 points, p=0.041). CONCLUSIONS: Azathioprine-treated
      patients' for AAV maintenance therapy showed a decline in physical abilities when
      compared to RTX at M24 in the MAINRITSAN trial. TRIAL REGISTRATION:
      ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00748644.

PMID- 27049409
TI  - Celebrating National Public Health Week.

PMID- 27049410
TI  - National Public Health Week: Small Steps Toward Big Change.

PMID- 27049412
TI  - A Public Health of Consequence: Review of the May 2016 Issue of AJPH.

PMID- 27049413
TI  - Emergency Care for Homeless Patients: A Window Into the Health Needs of
      Vulnerable Populations.

PMID- 27049414
TI  - Social Isolation, Loneliness, and Living Alone: Identifying the Risks for Public
      Health.

PMID- 27049415
TI  - The Continuing Development of Health Disparities Research on Lesbian, Gay,
      Bisexual, and Transgender Individuals.

PMID- 27049416
TI  - When Will Presidential Candidates Ask, "What Do Women Want in Health Care?".

PMID- 27049417
TI  - Wood Responds.

PMID- 27049418
TI  - Mainstream Health Care in Taiwan's Prisons: A Model for Expanding Medicaid
      Coverage to Incarcerated Americans.

PMID- 27049419
TI  - Being Fair in Universal Health Coverage: Prioritize Public Health Services for
      Low- and Middle-Income Countries.

PMID- 27049420
TI  - Living and Dying at the Crossroads: Racism, Embodiment, and Why Theory Is
      Essential for a Public Health of Consequence.

PMID- 27049424
TI  - Lifetime Prevalence of Suicide Attempts Among Sexual Minority Adults by Study
      Sampling Strategies: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Previous reviews have demonstrated a higher risk of suicide attempts
      for lesbian, gay, and bisexual (LGB) persons (sexual minorities), compared with
      heterosexual groups, but these were restricted to general population studies,
      thereby excluding individuals sampled through LGB community venues. Each sampling
      strategy, however, has particular methodological strengths and limitations. For
      instance, general population probability studies have defined sampling frames but
      are prone to information bias associated with underreporting of LGB identities.
      By contrast, LGB community surveys may support disclosure of sexuality but
      overrepresent individuals with strong LGB community attachment. OBJECTIVES: To
      reassess the burden of suicide-related behavior among LGB adults, directly
      comparing estimates derived from population- versus LGB community-based samples.
      SEARCH METHODS: In 2014, we searched MEDLINE, EMBASE, PsycInfo, CINAHL, and
      Scopus databases for articles addressing suicide-related behavior (ideation,
      attempts) among sexual minorities. SELECTION CRITERIA: We selected quantitative
      studies of sexual minority adults conducted in nonclinical settings in the United
      States, Canada, Europe, Australia, and New Zealand. DATA COLLECTION AND ANALYSIS:
      Random effects meta-analysis and meta-regression assessed for a difference in
      prevalence of suicide-related behavior by sample type, adjusted for study or
      sample-level variables, including context (year, country), methods (medium,
      response rate), and subgroup characteristics (age, gender, sexual minority
      construct). We examined residual heterogeneity by using tau(2). MAIN RESULTS: We
      pooled 30 cross-sectional studies, including 21,201 sexual minority adults,
      generating the following lifetime prevalence estimates of suicide attempts: 4%
      (95% confidence interval [CI] = 3%, 5%) for heterosexual respondents to
      population surveys, 11% (95% CI = 8%, 15%) for LGB respondents to population
      surveys, and 20% (95% CI = 18%, 22%) for LGB respondents to community surveys
      (Figure 1). The difference in LGB estimates by sample type persisted after we
      accounted for covariates with meta-regression. Sample type explained 33% of the
      between-study variability. AUTHOR'S CONCLUSIONS: Regardless of sample type
      examined, sexual minorities had a higher lifetime prevalence of suicide attempts
      than heterosexual persons; however, the magnitude of this disparity was
      contingent upon sample type. Community-based surveys of LGB people suggest that
      20% of sexual minority adults have attempted suicide. PUBLIC HEALTH IMPLICATIONS:
      Accurate estimates of sexual minority health disparities are necessary for public
      health monitoring and research. Most data describing these disparities are
      derived from 2 sample types, which yield different estimates of the lifetime
      prevalence of suicide attempts. Additional studies should explore the
      differential effects of selection and information biases on the 2 predominant
      sampling approaches used to understand sexual minority health.

PMID- 27049425
TI  - Understanding Adolescent Perceptions on E-Cigarettes Is Vital.

PMID- 27049426
TI  - Bostean et al. Respond.

PMID- 27049427
TI  - Metzl Responds.

PMID- 27049428
TI  - Seasonal Influence on Mass Shootings.

PMID- 27049429
TI  - Supporting Syrian Refugees: The Need for a Multidisciplinary Action Plan.

PMID- 27049430
TI  - Syrian Refugees Constitute 20% of Jordan's Population.

PMID- 27049431
TI  - McNeely and Morland Respond.

PMID- 27049432
TI  - Research on Spousal Violence: Toward a Balanced and Rigorous Approach.

PMID- 27049433
TI  - Ismayilova Responds.

PMID- 27049434
TI  - Mildly reduced less defective graphene oxide/sulfur/carbon nanotube composite
      films for high-performance lithium-sulfur batteries.
AB  - The microstructures and properties of the carbonaceous matrices in the cathodes
      of lithium-sulfur (Li-S) batteries have strong effects on their performances. We
      prepared a ternary composite cathode of mildly reduced less defective graphene
      oxide (mrLGO), sulfur, and carbon nanotubes (CNTs) by filtration for Li-S
      batteries. This battery showed a high initial specific capacity of 1219 mA h g(
      1) at 0.2 C and a stable specific capacity of around 1000 mA h g(-1) after 200
      cycles with a coulombic efficiency of 99%. Its excellent performance is mainly
      attributed to the good conductivity and residual oxygen containing groups of
      mrLGO, and the three-dimensional (3D) framework constructed using mrLGO sheets
      and CNTs. 

PMID- 27049435
TI  - Infrared imaging of small molecules in living cells: from in vitro metabolic
      analysis to cytopathology.
AB  - A major topic in InfraRed (IR) spectroscopic studies of living cells is the
      complexity of the vibrational spectra, involving hundreds of overlapping
      absorption bands from all the cellular components present at detectable
      concentrations. We focus on the relative contribution of both small-molecule
      metabolites and macromolecules, while defining the spectroscopic properties of
      cells and tissue in the middle IR (midIR) region. As a consequence, we show the
      limitations of current interpretative schemes that rely on a small number of
      macromolecules for IR band assignment. The discussion is framed specifically
      around the glycolytic metabolism of cancer cells because of the potential
      pharmacological applications. Several metabolites involved in glycolysis by A549
      lung cancer cells can be identified by this approach, which we refer to as
      Correlated Cellular Spectro-Microscopy (CSM). It is noteworthy that the rate of
      formation or consumption of specific molecules could be quantitatively assessed
      by this approach. We now extend this analysis to the two-dimensional case by
      performing IR imaging on single cells and cell clusters, detecting variations of
      metabolite concentration in time and space across the sample. The molecular
      detail obtained from this analysis allows its use in evaluating the
      pharmacological effect of inhibitors of glycolytic enzymes with potential
      consequences for in vitro drug testing. Finally we highlight the implications of
      the spectral contribution from cellular metabolites on applications in IR
      spectral cytopathology (SCP).

PMID- 27049436
TI  - Royal Jelly Constituents Increase the Expression of Extracellular Superoxide
      Dismutase through Histone Acetylation in Monocytic THP-1 Cells.
AB  - Extracellular superoxide dismutase (EC-SOD) is one of the main SOD isozymes and
      plays an important role in the prevention of cardiovascular diseases by
      accelerating the dismutation reaction of superoxide. Royal jelly includes 10
      hydroxy-2-decenoic acid (10H2DA, 2), which regulates the expression of various
      types of genes in epigenetics through the effects of histone deacetylase (HDAC)
      antagonism. The expression of EC-SOD was previously reported to be regulated
      epigenetically through histone acetylation in THP-1 cells. Therefore, we herein
      evaluated the effects of the royal jelly constituents 10-hydroxydecanoic acid
      (10HDA, 1), sebacic acid (SA, 3), and 4-hydroperoxy-2-decenoic acid ethyl ester
      (4-HPO-DAEE, 4), which is a derivative of 2, on the expression of EC-SOD in THP-1
      cells. The treatment with 1 mM 1, 2, or 3 or 100 MUM 4 increased EC-SOD
      expression and histone H3 and H4 acetylation levels. Moreover, the enrichment of
      acetylated histone H4 was observed in the proximal promoter region of EC-SOD and
      was caused by the partial promotion of ERK phosphorylation (only 4) and
      inhibition of HDAC activities, but not by the expression of HDACs. Overall, 4
      exerted stronger effects than 1, 2, or 3 and has potential as a candidate or lead
      compound against atherosclerosis. 

PMID- 27049437
TI  - Formation of palladium concave nanocrystals via auto-catalytic tip overgrowth by
      interplay of reduction kinetics, concentration gradient and surface diffusion.
AB  - A clear understanding of the growth mechanism involved in the shape-controlled
      synthesis of noble-metal nanocrystals with concave surfaces can provide useful
      information for the rational design of novel anisotropic nanostructures with
      controllable properties. In this paper, we conducted a systematic study of the
      detailed growth mechanism of the Pd arrow-headed tripods and revealed how the
      formation of the concave Pd nanocrystals was collectively controlled by the
      reduction kinetics, concentration gradient of Pd precursors, and surface
      diffusion of atoms. The formation of the arrow-headed tripods can be attributed
      to an auto-catalytic tip overgrowth process, where the Pd triangular nanoplate
      seeds formed under a suitably slow reduction rate can auto-catalyze the
      dehydrogenation of benzyl alcohol to generate hydrogen atoms [H]. The presence of
      [H] further dramatically accelerates the reduction of Pd(acac)2, which introduces
      a concentration gradient of Pd precursors in our non-stirring synthesis system
      and facilitates the kinetically-controlled tip overgrowth under a concentration
      gradient to form tripods with troughs on the arms. The final shapes of the
      concave nanocrystals depend on the relative rate of atom deposition and surface
      diffusion of atoms, which can be tuned by manipulating the reaction conditions
      such as the reaction temperature and the stirring conditions. This study presents
      a new possibility for the rational synthesis of various Pd nanostructures by
      manipulating the auto-catalytic process and tuning the relative rate of atom
      deposition and surface diffusion of atoms, which provides useful information for
      understanding the growth mechanism and the design of other anisotropic noble
      metal nanostructures. 

PMID- 27049438
TI  - Assessing the Accuracy of Various Ab Initio Methods for Geometries and Excitation
      Energies of Retinal Chromophore Minimal Model by Comparison with CASPT3 Results.
AB  - The effect of the quality of the ground-state geometry on excitation energies in
      the retinal chromophore minimal model (PSB3) was systematically investigated
      using various single- (within Moller-Plesset and coupled-cluster frameworks) and
      multiconfigurational [within complete active space self-consistent field (CASSCF)
      and CASSCF-based perturbative approaches: second-order CASPT2 and third-order
      CASPT3] methods. Among investigated methods, only CASPT3 provides geometry in
      nearly perfect agreement with the CCSD(T)-based equilibrium structure. The second
      goal of the present study was to assess the performance of the CASPT2
      methodology, which is popular in computational spectroscopy of retinals, in
      describing the excitation energies of low-lying excited states of PSB3 relative
      to CASPT3 results. The resulting CASPT2 excitation energy error is up to 0.16 eV
      for the S0 -> S1 transition but only up to 0.06 eV for the S0 -> S2 transition.
      Furthermore, CASPT3 excitation energies practically do not depend on modification
      of the zeroth-order Hamiltonian (so-called IPEA shift parameter), which does
      dramatically and nonsystematically affect CASPT2 excitation energies. 

PMID- 27049439
TI  - Spinal cord lesions shrink peripersonal space around the feet, passive
      mobilization of paraplegic limbs restores it.
AB  - Peripersonal space (PPS) is the space surrounding us within which we interact
      with objects. PPS may be modulated by actions (e.g. when using tools) or sense of
      ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a
      tool may induce a sense of ownership over it. Conversely, inducing ownership over
      a rubber hand may activate brain regions involved in motor control. However, the
      extent to which PPS is modulated by action-dependent or ownership-dependent
      mechanisms remains unclear. Here, we explored the PPS around the feet and the
      sense of ownership over lower limbs in people with Paraplegia following Complete
      spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their
      upper body but have lost all sensory-motor functions in their lower body (e.g.
      lower limbs). We tested whether PPS alterations reflect the topographical
      representations of various body parts. We found that the PPS around the feet was
      impaired in PCL who however had a normal representation of the PPS around the
      hands. Significantly, passive mobilization of paraplegic limbs restored the PPS
      around the feet suggesting that activating action representations in PCL brings
      about short-term changes of PPS that may thus be more plastic than previously
      believed. 

PMID- 27049440
TI  - Frog skin cultures secrete anti-yellow fever compounds.
AB  - There is an urgent need to develop novel antimicrobial substances. Antimicrobial
      peptides (AMPs) are considered as promising candidates for future therapeutic
      use. Because of the re-emergence of the Flavivirus infection, and particularly
      the yellow fever virus (YFV), we have compared the antiviral activities from skin
      secretions of seven different frog species against YFV (strain 17D). Secretions
      from Sphaenorhynchus lacteus, Cryptobatrachus boulongeri and Leptodactylus fuscus
      displayed the more powerful activities. S. lacteus was found to inhibit viral
      lysis of Vero E6 cells even at the highest viral concentration evaluated of 10
      LD50. We also report the identification of a novel frenatin-related peptide from
      S. lacteus and found that this peptide-on its own-can lead to 35% protection
      against YVF, while displaying no cytotoxicity against somatic cells even at
      fivefold higher concentrations. These results are attractive and support the need
      for continued exploration of new sources of AMPs from frog skin secretions such
      as those described here in the development of new compounds for the treatment of
      infectious diseases in general and specific viral infections in particular.

PMID- 27049441
TI  - Inhibition of bacterial undecaprenyl pyrophosphate synthase by small fungal
      molecules.
AB  - Viridicatumtoxin and spirohexaline, small fungal molecules with a tetracyclic
      scaffold and an additional spirobicyclic ring in common, were found to inhibit
      bacterial undecaprenyl pyrophosphate (UPP) synthase with IC50 values of 4 and 9
      MUm, respectively. These molecules showed weak inhibitory activity against
      catalytically related enzymes such as bacterial octaprenyl pyrophosphate synthase
      and yeast dehydrodolichyl pyrophosphate synthase, indicating that the compounds
      preferentially inhibit UPP synthase. They showed antimicrobial activity,
      particularly against Gram-positive bacteria including methicillin-resistant
      Staphylococcus aureus (MRSA). Furthermore, molecular modeling strongly suggested
      that the hydrophobic spirobicyclic ring of viridicatumtoxin interacts with three
      hydrophobic clefts of the active site in MRSA UPP synthase.

PMID- 27049442
TI  - Optical phase conjugation assisted scattering lens: variable focusing and 3D
      patterning.
AB  - Variable light focusing is the ability to flexibly select the focal distance of a
      lens. This feature presents technical challenges, but is significant for optical
      interrogation of three-dimensional objects. Numerous lens designs have been
      proposed to provide flexible light focusing, including zoom, fluid, and liquid
      crystal lenses. Although these lenses are useful for macroscale applications,
      they have limited utility in micron-scale applications due to restricted
      modulation range and exacting requirements for fabrication and control. Here, we
      present a holographic focusing method that enables variable light focusing
      without any physical modification to the lens element. In this method, a
      scattering layer couples low-angle (transverse wave vector) components into a
      full angular spectrum, and a digital optical phase conjugation (DOPC) system
      characterizes and plays back the wavefront that focuses through the scattering
      layer. We demonstrate micron-scale light focusing and patterning over a wide
      range of focal distances of 22-51 mm. The interferometric nature of the focusing
      scheme also enables an aberration-free scattering lens. The proposed method
      provides a unique variable focusing capability for imaging thick specimens or
      selective photoactivation of neuronal networks.

PMID- 27049443
TI  - Evaluation of Environmental Sample Analysis Methods and Results Reporting in the
      National Children's Study Vanguard Study.
AB  - During the initial Vanguard phase of the U.S. National Children's Study (NCS),
      about 2000 tap water, surface wipe, and air samples were collected and analyzed
      immediately. The shipping conditions, analysis methods, results, and laboratory
      performance were evaluated to determine the best approaches for use in the NCS
      Main Study. The main conclusions were (1) to employ established sample analysis
      methods, when possible, and alternate methodologies only after careful
      consideration with method validation studies; (2) lot control and prescreening
      sample collection materials are important quality assurance procedures; (3)
      packing samples correctly requires careful training and adjustment of shipping
      conditions to local conditions; (4) trip blanks and spiked samples should be
      considered for samplers with short expiration times and labile analytes; (5) two
      study-specific results reports should be required: laboratory electronic data
      deliverables (EDD) of sample results in a useable electronic format (CSV or SEDD
      XML/CSV) and a data package with sample results and supporting information in PDF
      format. These experiences and lessons learned can be applied to any long-term
      study.

PMID- 27049444
TI  - Boronic Acid-Functionalized Particles with Flexible Three-Dimensional Polymer
      Branch for Highly Specific Recognition of Glycoproteins.
AB  - A novel organic-inorganic hybrid particle with high hydrophilicity three
      dimensional boronic acid functional polymer branches was facilely synthesized
      through thiol-ene surface-initiated click reaction, by which the target
      glycoprotein could be captured selectively in the 5000-fold disrupting protein.
      This highest selectivity ever reported demonstrated that this boronic acid
      functionalized particle exhibited great potential in the recognition of cis-diol
      containing biomolecules, including the glycoproteins. 

PMID- 27049445
TI  - Relationship of genioglossus muscle activation and severity of obstructive sleep
      apnea and hypopnea syndrome among Chinese patients.
AB  - CONCLUSION: Variability of GGEMG at sleep onset is associated with apnea severity
      in OSA patients. At sleep onset, a lower decline in GGEMG might suggest a more
      severe OSA. OBJECTIVE: The goal of this study was to evaluate genioglossus (GG)
      activation in the Chinese population at early sleep onset, and clarify the
      relationship of GG activation and the apnea severity in patients with Obstructive
      Sleep Apnea (OSA). METHODS: Thirty-five OSA patients and 10 normal controls
      underwent overnight polysomnography with synchronous genioglossus
      electromyography (GGEMG) using intra-oral electrodes. The upper airway (UA)
      anatomy was evaluated by three-dimensional computer tomography (3D-CT) in all
      subjects. RESULTS: The average GGEMG and tonic GGEMG were higher in the apnea
      patients than in the normal controls during wakefulness and early sleep onset
      period (three breaths) (p < 0.01). Eight OSA patients had increased GGEMG at
      sleep onset and 27 patients had decreased GGEMG values. Between the two groups,
      there were significant differences in the apnea-hypopnea index (AHI), minimal
      cross-sectional airway area (mCAS) and minimal lateral airway dimension (mLAT) at
      velopharynx (p < 0.05). The change in GGEMG, phasic GGEMG and tonic GGEMG from
      awake to sleep showed positive correlations with AHI and negative correlations
      with velopharynx (mLAT and mCAS) (p < 0.05).

PMID- 27049446
TI  - Effects of 24-week Tai Chi exercise on the knee and ankle proprioception of older
      women.
AB  - This study examined the effects of regular Tai Chi (TC) exercise on the
      kinaesthesia of the knee and ankle joints of older women. A total of 43 women
      aged 55-68 years participated in this study. In a 24-week study period, the TC
      group (n = 22) underwent an organized TC exercise, whereas the control group (n =
      21) maintained a sedentary lifestyle. Customized instruments were used to measure
      the threshold for the detection of the passive motion of the knee and ankle
      joints. After 24 weeks, the TC group showed a significantly smaller threshold for
      the detection of passive motion of knee extension (31.4%, p = 0.009), knee
      flexion (27.0%, p = 0.044), and ankle dorsal flexion (28.9%, p = 0.014) than the
      control group. Other comparisons showed no significant differences. The 24-week
      TC exercise benefited the lower-limb kinaesthesia of the knee joint flexion and
      extension and ankle dorsal flexion.

PMID- 27049447
TI  - Functional Magnetic Resonance Imaging Study of Brain Activity Associated With
      Pitch Adaptation During Phonation in Healthy Women Without Voice Disorders.
AB  - OBJECTIVES: This functional magnetic resonance imaging (fMRI) study investigated
      the brain activity associated with pitch adaptation during phonation in healthy
      women without voice disorders. STUDY DESIGN: This is an interventional
      prospective study. METHODS: Sixteen healthy women (mean age: 24.3 years)
      participated in a blocked design fMRI experiment involving two phonation
      (comfortable phonation and high-pitched phonation) and exhalation (prolonged
      exhalation) tasks. BrainVoyager QX Version 2.4 software was used for group-level
      general linear model analysis (q[FDR] < 0.05). RESULTS: Analyses showed a
      significant main effect of phonation with pitch adaptation compared with rest
      period in the bilateral precentral gyrus, superior frontal gyrus, posterior
      cingulate gyrus, superior and middle temporal gyrus, insula and cerebellum, left
      middle and inferior frontal gyrus, right lingual gyrus, cingulate gyrus, and
      thalamus. Statistical results also identified a significant main effect of
      exhalation compared with rest period in the bilateral precentral gyrus,
      cerebellum, right lingual gyrus, thalamus, and left supramarginal gyrus. In
      addition, a significant main effect of phonation was found in the bilateral
      superior temporal gyrus and right insula, as well as in the left midbrain
      periaqueductal gray for high-pitched phonation only. CONCLUSIONS: We demonstrated
      that a blocked design fMRI is sensitive enough to define a widespread network of
      activation associated with phonation involving pitch variation. The results of
      this study will be implemented in our future research on phonation and its
      disorders.

PMID- 27049448
TI  - Relationship Between Acoustic Measurements and Self-evaluation in Patients With
      Voice Disorders.
AB  - OBJECTIVE: The study aimed to determine whether there is a relationship between
      acoustic measures and self-evaluation in patients with voice disorders. STUDY
      DESIGN: This is a descriptive, transversal, and observational study. METHODS:
      Patients (257) who answered the Voice Handicap Index protocols (VHI) and the
      Voice Symptoms Scale (VoiSS) and recorded the vowel /epsilon/ were included.
      Standard deviation (SD) measures of the fundamental frequency (F0), jitter,
      shimmer, and the glottal to noise excitation ratio (GNE) vowel /epsilon/ were
      taken. RESULTS: There was a weak positive correlation between all scores of VoiSS
      and the SD of the F0 and jitter. The overall scores, physical limitation, and
      VoiSS showed weak positive correlations with shimmer. The overall scores,
      limitation, and emotional VoiSS showed weak negative correlations with the GNE.
      The VHI did not correlate with any of the acoustic measurements. There was no
      difference in the mean of the acoustic measures of the SD of F0, jitter, and GNE
      because of a voice problem detected from the cutoff points of VoiSS. There was no
      difference in any of the acoustic measurements when patients with and without
      voice problems were compared from VHI cutoffs. CONCLUSIONS: There is a
      correlation between the scores of VoiSS and acoustic measurements. Patients with
      self-reported voice problems in VoiSS present greater deviations in acoustic
      measures, mainly in jitter. There is no correlation between the VHI scores and
      the acoustic measures and no difference in the averages of these measures between
      patients with and without voice problems detected from the VHI cutoffs.

PMID- 27049449
TI  - Evolving Spiking Neural Networks for Recognition of Aged Voices.
AB  - The aging of the voice, known as presbyphonia, is a natural process that can
      cause great change in vocal quality of the individual. This is a relevant problem
      to those people who use their voices professionally, and its early identification
      can help determine a suitable treatment to avoid its progress or even to
      eliminate the problem. This work focuses on the development of a new model for
      the identification of aging voices (independently of their chronological age),
      using as input attributes parameters extracted from the voice and glottal
      signals. The proposed model, named Quantum binary-real evolving Spiking Neural
      Network (QbrSNN), is based on spiking neural networks (SNNs), with an
      unsupervised training algorithm, and a Quantum-Inspired Evolutionary Algorithm
      that automatically determines the most relevant attributes and the optimal
      parameters that configure the SNN. The QbrSNN model was evaluated in a database
      composed of 120 records, containing samples from three groups of speakers. The
      results obtained indicate that the proposed model provides better accuracy than
      other approaches, with fewer input attributes.

PMID- 27049450
TI  - Improvement in the Reflux Symptom Index Following Surgery for Cricopharyngeal
      Dysfunction.
AB  - OBJECTIVES: Gastroesophageal reflux may contribute to the development of
      cricopharyngeal dysfunction and Zenker's diverticulum. Common dictum suggests
      that if upper esophageal sphincter tone is reduced through cricopharyngeal
      myotomy, symptoms of laryngopharyngeal reflux may worsen. We hypothesized that
      patients who undergo myotomy should show decreased dysphagia symptoms with
      concurrent worsening of reflux symptomatology and that these changes would be
      greater in those patients undergoing complete versus partial myotomy. METHODS: A
      retrospective chart review was performed for patients who underwent endoscopic or
      open cricopharyngeal myotomy, with or without Zenker's diverticulectomy.
      Preoperative and postoperative reflux symptomatology was subjectively measured
      with the Reflux Symptom Index (RSI), and dysphagia symptomatology was measured
      with the Eating Assessment Tool 10 (EAT-10). Patients who underwent partial
      myotomy via endoscopic stapling of Zenker's diverticulum were compared with
      patients who underwent complete myotomy (either endoscopic laser-assisted or via
      an open transcervical approach). The patients were further subdivided into three
      groups for data analysis: endoscopic staple diverticulotomy, laser
      cricopharyngeal myotomy, and open approach. RESULTS: A total of 41 patient charts
      were reviewed. Of these 41 patients, 17 underwent endoscopic stapler-assisted
      diverticulotomy, 4 underwent endosopic laser-assisted cricopharyngeal myotomy,
      and 20 underwent open transcervical cricopharyngeal myotomy, with
      diverticulectomy as indicated. Mean pre- and postoperative RSIs were 21.8 and
      8.9, respectively (P < 0.001). Mean pre- and postoperative EAT-10 scores were
      19.1 and 5.0, respectively (P < 0.001). CONCLUSIONS: Patients' reflux symptoms
      significantly improved after cricopharyngeal myotomy, with significant
      improvement in dysphagia symptoms. Concern for worsening of reflux symptoms
      following surgery does not appear to be clinically common.

PMID- 27049451
TI  - The Moderating Effect of Frequent Singing on Voice Aging.
AB  - The effects of aging on voice production are well documented, including changes
      in loudness, pitch, and voice quality. However, one important and clinically
      relevant question that remains concerns the possibility that the aging of voice
      can be prevented or at least delayed through noninvasive methods. Indeed,
      discovering natural means to preserve the integrity of the human voice throughout
      aging could have a major impact on the quality of life of elderly adults. The
      objective of this study was therefore to examine the potentially positive effect
      of singing on voice production. To this aim, a group of 72 healthy nonsmoking
      adults (20-93 years old) was recruited and separated into three groups based on
      their singing habits. Several voice parameters were assessed (fundamental
      frequency [f0] mean, f0 standard deviation [SD], f0 minimum and f0 maximum, mean
      amplitude and amplitude SD, jitter, shimmer, and harmonic-to-noise ratio) during
      the sustained production of vowel /a/. Other parameters were assessed during
      standardized reading passage (speaking f0, speaking f0 SD). As was expected, age
      effects were found on most acoustic parameters with significant sex differences.
      Importantly, moderation analyses revealed that frequent singing moderates the
      effect of aging on most acoustic parameters. Specifically, in frequent singers,
      there was no decrease in the stability of pitch and amplitude with age,
      suggesting that the voice of frequent singers remains more stable in aging than
      the voice of non-singers, and more generally, providing empirical evidence for a
      positive effect of singing on voice in aging.

PMID- 27049452
TI  - A Case Report: Hybrid Treatment Approach to Lipoid Proteinosis of the Larynx.
AB  - OBJECTIVE: Previous research on treatment of lipoid proteinosis has focused on
      genetic etiology and clinical diagnosis of this rare laryngeal disorder. However,
      few studies on this disorder have examined treatment methods directed at
      improving voice qualities. The purpose of this study was to examine a novel
      hybrid treatment approach and its improvements in the patient's voice quality.
      STUDY DESIGN AND METHODS: In this case study, a 27-year-old man complaining of
      hoarseness of voice and effortful phonation was diagnosed with lipoid
      proteinosis. He was then prescribed a combination of surgical intervention and
      voice therapy to improve his overall voice quality. RESULTS: The results of the
      posttreatment evaluation demonstrate significant improvements in both objective
      and subjective voice quality measurements. CONCLUSION: A further examination of
      this hybrid approach in the treatment of lipoid proteinosis is warranted to
      determine its efficacy.

PMID- 27049453
TI  - Substance use in rural adolescents: The impact of social capital, anti-social
      capital, and social capital deprivation.
AB  - Middle- and high-school substance use is a pressing public health problem in the
      United States. Despite similar or, in some cases, elevated rates of substance use
      among rural youth, much of the extant research on adolescent substance use has
      focused on urban areas. The current study aims to uncover forms of social capital
      (e.g., ethnic identity), social capital deprivation (e.g., parent-child
      conflict), and anti-social capital (e.g., delinquent friends) that impact the use
      of alcohol, cigarettes, and marijuana in a sample of middle- and high-school
      students from the rural south. It was hypothesized that social capital factors
      would be associated with decreased substance use while social capital deprivation
      and anti-social capital factors would be associated with increased substance use.
      The hypotheses were tested using logistic regression models with generalized
      estimating equations. The findings indicated that for middle school youth, anti
      social capital in the form of aggression and delinquent friends was significantly
      associated with an increased likelihood of using alcohol, cigarettes, and
      marijuana. For high school students, anti-social capital in the form of
      aggression and delinquent friends and social capital deprivation in the form of
      neighborhood crime were significantly associated with an increased likelihood of
      using alcohol, cigarettes, and marijuana. Violent behavior was also significantly
      associated with an increased likelihood of using marijuana. Females reported less
      substance use in both middle and high school; reports of use increased with age.
      Implications are discussed. Given the salience of social capital deprivation,
      substance use programs should emphasize the skills necessary to avoid or
      disengage from antisocial relationships.

PMID- 27049454
TI  - Research capacity in Africa--will the sun rise again?

PMID- 27049455
TI  - Nonhomologous end joining of complex DNA double-strand breaks with proximal
      thymine glycol and interplay with base excision repair.
AB  - DNA double-strand breaks induced by ionizing radiation are often accompanied by
      ancillary oxidative base damage that may prevent or delay their repair. In order
      to better define the features that make some DSBs repair-resistant, XLF-dependent
      nonhomologous end joining of blunt-ended DSB substrates having the oxidatively
      modified nonplanar base thymine glycol at the first (Tg1), second (Tg2), third
      (Tg3) or fifth (Tg5) positions from one 3' terminus, was examined in human whole
      cell extracts. Tg at the third position had little effect on end-joining even
      when present on both ends of the break. However, Tg as the terminal or
      penultimate base was a major barrier to end joining (>10-fold reduction in
      ligated products) and an absolute barrier when present at both ends. Dideoxy
      trapping of base excision repair intermediates indicated that Tg was excised from
      Tg1, Tg2 and Tg3 largely if not exclusively after DSB ligation. However, Tg was
      rapidly excised from the Tg5 substrate, resulting in a reduced level of DSB
      ligation, as well as slow concomitant resection of the opposite strand. Ligase
      reactions containing only purified Ku, XRCC4, ligase IV and XLF showed that
      ligation of Tg3 and Tg5 was efficient and only partially XLF-dependent, whereas
      ligation of Tg1 and Tg2 was inefficient and only detectable in the presence of
      XLF. Overall, the results suggest that promoting ligation of DSBs with proximal
      base damage may be an important function of XLF, but that Tg can still be a major
      impediment to repair, being relatively resistant to both trimming and ligation.
      Moreover, it appears that base excision repair of Tg can sometimes interfere with
      repair of DSBs that would otherwise be readily rejoined.

PMID- 27049456
TI  - Khat-induced liver injuries: A report of two cases.
AB  - Khat is consumed for recreational purposes in many countries, including Yemen,
      where >50% of adults chew khat leaves regularly. A wide spectrum of khat-induced
      liver injuries has been reported in the literature. Herein, we report two
      patients with khat-induced liver injury. Both patients clinically presented with
      acute hepatitis, one of whom showed radiological evidence of hepatic outflow
      obstruction. Based on the histological tests, both patients had acute hepatitis,
      which indicated drug-induced liver injury (DILI) on a background of chronic
      hepatitis and portal fibrosis; of the two, one presented with symptoms of immune
      mediated liver injury. 

PMID- 27049458
TI  - Dual inhibition of oncogenic targets for B-cell malignancies.

PMID- 27049459
TI  - Therapeutic targeting of complement to modify disease course and improve outcomes
      in neurological conditions.
AB  - The recognition that complement proteins are abundantly present and can have
      pathological roles in neurological conditions offers broad scope for therapeutic
      intervention. Accordingly, an increasing number of experimental investigations
      have explored the potential of harnessing the unique activation pathways,
      proteases, receptors, complexes, and natural inhibitors of complement, to
      mitigate pathology in acute neurotrauma and chronic neurodegenerative diseases.
      Here, we review mechanisms of complement activation in the central nervous system
      (CNS), and explore the effects of complement inhibition in cerebral ischemic
      reperfusion injury, traumatic brain injury, spinal cord injury, Alzheimer's
      disease, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's
      disease. We consider the challenges and opportunities arising from these studies.
      As complement therapies approach clinical translation, we provide perspectives on
      how promising complement-targeted therapeutics could become part of novel and
      effective future treatment options to improve outcomes in the initiation and
      progression stages of these debilitating CNS disorders.

PMID- 27049457
TI  - Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class,
      oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory
      lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial.
AB  - BACKGROUND: Treatment options for patients with relapsed or refractory lymphoma
      and multiple myeloma are limited. CUDC-907 is an oral, first-in-class, small
      molecule that is designed to inhibit both histone deacetylase (HDAC) and PI3K
      enzymes, which are members of common oncogenic pathways in haematological
      malignancies. We aimed to assess overall safety and preliminary activity in this
      dose-escalation study of CUDC-907 monotherapy in patients with relapsed or
      refractory lymphoma and multiple myeloma. METHODS: This open-label, first-in-man,
      phase 1 trial recruited adult patients (aged >=18 years) with lymphoma or
      multiple myeloma who were refractory to or had relapsed after two or more
      previous regimens, from four US cancer centres. CUDC-907 was orally administered
      in a standard 3 + 3 dose-escalation design at four different dosing schedules, to
      which participants were sequentially assigned as follows: once daily,
      intermittently (twice or three times weekly; simultaneous enrolment), and daily
      for 5 days followed by a 2-day break (5/2), in 21-day cycles. Dosing started at
      30 mg for the once-daily schedule and 60 mg for other schedules, escalating in 30
      mg increments. Patients continued to receive CUDC-907 until disease progression
      or until other treatment discontinuation criteria were met. The primary objective
      was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose,
      assessed in patients who received at least 66% of cycle 1 doses without
      modification and those who had a dose-limiting toxicity (DLT) in cycle 1
      irrespective of dose modification. We assessed safety in all patients who
      received at least one dose of study drug. This ongoing trial is registered at
      ClinicalTrials.gov, number NCT01742988. FINDINGS: Between Jan 23, 2013, and July
      27, 2015, we enrolled 44 patients, of whom ten were sequentially assigned to CUDC
      907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to three-times
      weekly (MTD 150 mg), and seven to the 5/2 dosing schedule (MTD 60 mg). 37 (84%)
      patients had discontinued study drug as a result of progressive disease or
      clinical signs of progressive disease at the data cutoff. Four DLTs occurred in
      three of 40 DLT-evaluable patients (diarrhoea and hyperglycaemia in one patient
      on 60 mg once daily, hyperglycaemia in one patient on 150 mg twice weekly, and
      diarrhoea in one patient on 150 mg three times weekly); no DLTs were reported in
      patients on the 5/2 schedule. Grade 3 or worse adverse events occurred in 19
      (43%) of 44 patients, the most common of which were thrombocytopenia (in nine
      [20%] of 44 patients), neutropenia (three [7%]), and hyperglycaemia (three [7%]).
      11 (25%) of 44 patients had serious adverse events, three of which were regarded
      as treatment related (epistaxis and the DLTs of diarrhoea and hyperglycaemia).
      Adverse events led to dose reductions in six (14%) patients and treatment
      discontinuation in seven (16%). Five (14%) of 37 response-evaluable patients
      achieved an objective response (two complete responses and three partial
      responses). All five responses occurred in the subgroup of patients with diffuse
      large B-cell lymphoma (DLBCL; n=9), and three occurred in those with transformed
      follicular lymphoma DLBCL (n=5). 21 (57%) of 37 response-evaluable patients had
      stable disease, including those with DLBCL, Hodgkin's lymphoma, and multiple
      myeloma. On the basis of these findings, we selected CUDC-907 60 mg on the 5/2
      dosing schedule as the recommended phase 2 dose. INTERPRETATION: The safety and
      tolerability profile of CUDC-907 and the promising preliminary evidence of
      response support continued development of CUDC-907 at the 60 mg 5/2 dosing
      schedule, alone and in combination with other therapies. A dose-expansion trial
      of this dose in patients with refractory and relapsed DLBCL in particular, is
      ongoing. FUNDING: Curis, Inc, and the Leukemia and Lymphoma Society.

PMID- 27049460
TI  - Molecular features of macrophage activation.
AB  - Cellular activation is mainly defined as the response of a cell to exogenous
      signals eventually leading to changes in protein expression and cellular
      function. Originally, macrophage activation was mainly associated with phagocytic
      function. Later other effector functions such as cytokine secretion, upregulation
      of cell surface receptors came into focus. For a while macrophage activation was
      classified as being either pro-inflammatory or anti-inflammatory and certain
      signal transduction pathways were associated with these two conditions. Most
      recent findings on transcriptional and epigenetic level, however, suggest that
      the molecular features of macrophage activation are significantly more complex.
      Here, we will introduce a novel and integrative model of macrophage activation.
      Albeit recognizing that macrophage activation cannot be reduced to nuclear
      processes, we will focus in this review on the most recent findings concerning
      transcriptional and epigenetic regulation of macrophage activation. Understanding
      the complexity of the central regulatory mechanisms in the nucleus will form a
      foundation for deciphering all the different effector functions that are
      associated with macrophage activation.

PMID- 27049461
TI  - Changes in lymphocyte properties after employment of the combination of
      carbamylation and oxidative stress, an in vitro study.
AB  - It is well known that oxidative stress and carbamylation alter macromolecule
      properties and functions. We evaluated the influence of sodium cyanate (NaOCN)
      and the combination of cyanate and hydrogen peroxide (H2O2) on nonenzymatic
      antioxidant capacity (NEAC), total thiols, reduced glutathione (GSH) and
      hydroperoxide level in mononuclear blood cells (MNCs). We also examined plasma
      membrane properties of MNCs using the spin labeling method in EPR spectroscopy
      (electron paramagnetic resonance spectroscopy). We showed that MNCs are resistant
      to cyanate treatment up to a concentration of 2mM (survival test). On the other
      hand, a significant loss of antioxidant defense of cells, e.g. NEAC upon NaOCN,
      H2O2 and the combination of cyanate and hydrogen peroxide was observed.
      Carbamylation slightly decreased GSH and the free thiol level, but H2O2 and its
      combination with NaOCN lead to a decrease in their amounts. A markedly higher
      level of hydroperoxides was only observed in the cells treated with H2O2. We
      found a significant decrease in lipid membrane fluidity at the depth of 12th and
      16th carbon atoms of fatty acids in lymphocytes treated with cyanate or H2O2. The
      combination of both substances acted synergistically and induced profound changes
      in comparison to cyanate and hydrogen peroxide used alone. 

PMID- 27049462
TI  - Asistole after electroconvusise therapy.

PMID- 27049463
TI  - Quantitative proteomic analysis of mice corneal tissues reveals angiogenesis
      related proteins involved in corneal neovascularization.
AB  - Corneal neovascularization (CNV) was induced in Balb/c mice by alkali burns in
      the central area of the cornea with a diameter of 2.5mm. After fourteen days, the
      cornea from one eye was collected for histological staining for CNV examination,
      while the cornea from the other eye of the same mouse was harvested for proteomic
      analysis. The label-free quantitative proteomic approach was applied to analyze
      five normal corneal tissues (normal group mice n=5) and five corresponding
      neovascularized corneal tissues (model group mice n=5). A total of 2124 proteins
      were identified, and 1682 proteins were quantified from these corneal tissues.
      Among these quantified proteins, 290 proteins were significantly changed between
      normal and alkali burned corneal tissues. Of these significantly changed
      proteins, 35 were reported or predicted as angiogenesis-related proteins. Then,
      these 35 proteins were analyzed using Ingenuity Pathway Analysis Software,
      resulting in 26 proteins enriched and connected to each other in the protein
      protein interaction network, such as Lcn-2, alphaB-crystallin and Serpinf1
      (PEDF). These three significantly changed proteins were selected for further
      Western blotting validation. Consistent with the quantitative proteomic results,
      Western blotting showed that Lcn-2 and alphaB-crystallin were significantly up
      regulated in CNV model, while PEDF was down-regulated. This study provided
      increased understanding of angiogenesis-related proteins involved in corneal
      vascular development, which will be useful in the ophthalmic clinic of
      specifically target angiogenesis. 

PMID- 27049464
TI  - Role of dietary antioxidant (-)-epicatechin in the development of beta
      lactoglobulin fibrils.
AB  - Under specific physico-chemical conditions beta-lactoglobulin is seen to form
      fibrils structurally highly similar to those that are formed by the amyloid-like
      proteins associated with neurodegenerative disorders, such as Alzheimer and
      Parkinson diseases. In the present study we provide insights on the possible role
      that the dietary flavonoid (-)-epicatechin plays on beta-lactoglobulin fibril
      formation. Fibril formation is induced by keeping beta-lactoglobulin solutions at
      pH2.0 and at a temperature of 80 degrees C for 24h. Atomic Force Microscopy
      measurements suggest that, by adding (-)-epicatechin in the solution, fibrils
      density is visibly lowered. This last observation is confirmed by Fluorescence
      Correlation Spectroscopy experiments. With the use of Fourier Transform IR
      spectroscopy we monitored the relative abundances of the secondary structures
      components during the heating process. We observed that in the presence of (-)
      epicatechin the spectral-weight exchange between different secondary structures
      is partially inhibited. Molecular Dynamics simulations have been able to provide
      an atomistic explanation of this experimental observation, showing that (-)
      epicatechin interacts with beta-lactoglobulin mainly via the residues that,
      normally in the absence of (-)-epicatechin, are involved in beta-sheet formation.
      Unveiling this molecular mechanism is an important step in the process of
      identifying suitable molecules apt at finely tuning fibril formation like it is
      desirable to do in food industry applications. 

PMID- 27049465
TI  - Within-cycle fluctuations in progesterone negatively predict changes in both in
      pair and extra-pair desire among partnered women.
AB  - Grebe et al. (2016) argued that women's sexual interest in their own partners may
      be under different hormonal regulation than their sexual desire for other men.
      They measured partnered women's salivary hormones and reports of attraction to
      different categories of men at two time points separated by one week. Change in
      progesterone positively predicted change in women's desire for their own
      partners, whereas change in estradiol was a negative predictor. These results are
      opposite to those we previously reported for the hormonal prediction of general
      sexual desire in a study that employed frequent hormone sampling across multiple
      menstrual cycles (Roney and Simmons, 2013). Here, to test replication of the
      Grebe et al. findings, we assessed hormonal predictors of targeted in-pair and
      extra-pair desire among the subset of the sample from our 2013 paper who reported
      being in romantic relationships. Contrary to Grebe et al. (2016), we found that
      within-cycle fluctuations in progesterone were negatively correlated with changes
      in women's desire for both their own partners and other men. In addition, both in
      pair and extra-pair desire were elevated within the fertile window and lowest
      during the luteal phase. Our findings contradict the idea that partner-specific
      desire has a unique form of hormonal regulation, and instead support a general
      elevation of sexual motivation associated with hormonal indices of fecundity.
      Discussion focuses on possible reasons for the discrepancies in findings between
      our study and that of Grebe et al. (2016), and on the evolved functions of
      women's sexual motivation.

PMID- 27049468
TI  - Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded
      with curcumin for breast cancer therapy.
AB  - The aim of this study was to evaluate therapeutic potential of curcumin-loaded
      poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and
      concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer
      treatment. The size and zeta potential of prepared NPs were about 228 +/- 5 nm
      and -23.3 mV, respectively. The entrapment efficiencies of polymer/drug weight
      ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and
      ConA-5CUR-NPs were found to be ~68, 55, 45, 70, 60 and 51%, respectively.
      Optimized NPs formulations in the freeze-dried form were assessed with their
      short-term stability for 30 days of storage at 4  degrees C and 25  degrees C.
      Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by
      double staining and flow cytometry results. The anticancer activity of ConA-CUR
      NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the
      results revealed that the ConA-CUR-NPs had better tumor cells decline activity. 

PMID- 27049467
TI  - Aberrant hnRNP K expression: All roads lead to cancer.
AB  - The classification of a gene as an oncogene or a tumor suppressor has been a
      staple of cancer biology for decades. However, as we delve deeper into the
      biology of these genes, this simple classification has become increasingly
      difficult for some. In the case of heterogeneous nuclear ribonuclear protein K
      (hnRNP K), its role as a tumor suppressor has recently been described in acute
      myeloid leukemia and demonstrated in a haploinsufficient mouse model. In
      contrast, data from other clinical correlation studies suggest that hnRNP K may
      be more fittingly described as an oncogene, due to its increased levels in a
      variety of malignancies. hnRNP K is a multifunctional protein that can regulate
      both oncogenic and tumor suppressive pathways through a bevy of chromatin-, DNA-,
      RNA-, and protein-mediated activates, suggesting its aberrant expression may have
      broad-reaching cellular impacts. In this review, we highlight our current
      understanding of hnRNP K, with particular emphasis on its apparently dichotomous
      roles in tumorigenesis. 

PMID- 27049466
TI  - Synergy Between Galphaz Deficiency and GLP-1 Analog Treatment in Preserving
      Functional beta-Cell Mass in Experimental Diabetes.
AB  - A defining characteristic of type 1 diabetes mellitus (T1DM) pathophysiology is
      pancreatic beta-cell death and dysfunction, resulting in insufficient insulin
      secretion to properly control blood glucose levels. Treatments that promote beta
      cell replication and survival, thus reversing the loss of beta-cell mass, while
      also preserving beta-cell function, could lead to a real cure for T1DM. The alpha
      subunit of the heterotrimeric Gz protein, Galphaz, is a tonic negative regulator
      of adenylate cyclase and downstream cAMP production. cAMP is one of a few
      identified signaling molecules that can simultaneously have a positive impact on
      pancreatic islet beta-cell proliferation, survival, and function. The purpose of
      our study was to determine whether mice lacking Galphaz might be protected, at
      least partially, from beta-cell loss and dysfunction after streptozotocin
      treatment. We also aimed to determine whether Galphaz might act in concert with
      an activator of the cAMP-stimulatory glucagon-like peptide 1 receptor, exendin-4
      (Ex4). Without Ex4 treatment, Galphaz-null mice still developed hyperglycemia,
      albeit delayed. The same finding held true for wild-type mice treated with Ex4.
      With Ex4 treatment, Galphaz-null mice were protected from developing severe
      hyperglycemia. Immunohistological studies performed on pancreas sections and in
      vitro apoptosis, cytotoxicity, and survival assays demonstrated a clear effect of
      Galphaz signaling on pancreatic beta-cell replication and death; beta-cell
      function was also improved in Galphaz-null islets. These data support our
      hypothesis that a combination of therapies targeting both stimulatory and
      inhibitory pathways will be more effective than either alone at protecting,
      preserving, and possibly regenerating beta-cell mass and function in T1DM. 

PMID- 27049472
TI  - Pharmacophore modeling and structure-based virtual screening to identify potent
      inhibitors targeting LuxP of Vibrio harveyi.
AB  - The main aim of the study is to identify molecules that can disrupt quorum
      sensing (QS) system of Vibrio harveyi and therefore perhaps the production of
      toxins. Recently, a novel class of dioxazaborocane derivatives has been found to
      block AI-2 QS by targeting LuxPQ, but the mechanism of protein inhibition is
      still unclear. In order to investigate the possible binding modes, all the
      derivatives were docked into the binding site of LuxP using induced fit docking
      (IFD). The computed binding affinity is in good agreement with the experimental
      data. Resultant protein-ligand complexes were simulated using Desmond module and
      the result revealed better binding of ligands in the binding site of LuxP. Both
      pharmacophore- and structure-based virtual screening was performed to identify
      novel hits against LuxP. A filtering protocol, including lipinski filters, number
      of rotatable bonds and three levels of docking precisions were used for the
      selection of hits with specific properties. The virtual screening results were
      then combined and analyzed, which retrieved six hits with significant Glide
      score, binding affinity toward LuxP. The pharmacokinetic properties of the
      retrieved hits are in the acceptable range. Enrichment calculation was performed
      to validate the final hits, to discriminate the active compounds from the
      inactive compounds. The identified hits could serve as a base for further drug
      development against LuxP of Vibrio harveyi.

PMID- 27049473
TI  - Outcome of patients with dual diagnosis in secondary psychiatric care.
AB  - BACKGROUND: Dual diagnosis (DD) is a common co-morbidity of mental illness and
      substance use disorder (SUD) and patients with DD are prone to complications.
      Better knowledge on the outcome, mortality and management of patients with DD in
      usual secondary psychiatric care would help to inform improved treatment
      strategies in the future. AIMS: To explore the functional outcome and mortality
      of patients with DD receiving psychiatric treatment. To assess the recognition of
      substance use disorders (SUDs) in terms of diagnosis, and the associations of
      clinically diagnosed SUDs with treatment-related variables. METHODS: The sample
      of 330 patients was collected by screening all currently treated patients with
      the Alcohol Use Disorders Identification Test (AUDIT) and a question about other
      substances used. The inclusion criteria were AUDIT >7 and/or reported use of
      other substances during the preceding 12 months. The Global Assessment of
      Functioning scale was used to assess functional outcomes during a 2-year follow
      up. Information concerning treatment and patient characteristics was collected
      retrospectively. RESULTS: Level of functioning remained stable among all study
      patients during follow-up. The mortality rate was not increased. Effective
      medication use was associated with improved functional outcomes. SUDs were
      underdiagnosed. A clinically diagnosed SUD seemed to have an impact on the
      regularity of appointments and the doses of prescribed medications. CONCLUSIONS:
      Given our results suggesting a stable level of functioning, patients with DD
      appear to be well managed within secondary psychiatric care. Attention should be
      paid to more precise diagnostics of SUDs and to effective use of medication.

PMID- 27049474
TI  - Sociosexuality, Commitment, Sexual Infidelity, and Perceptions of Infidelity:
      Data From the Second Love Web Site.
AB  - This study explored the association between sociosexuality (behavior, attitudes,
      and desire) and commitment to understand sexual infidelity in current
      relationships. We also explored how these variables were associated with
      attitudes toward infidelity. Participants were romantically involved
      heterosexuals (N = 252; 51 women, 201 men; Mage = 41.13, SD = 9.82) registered on
      a dating Web site directed at romantically involved individuals. Results showed
      that sociosexuality, alongside commitment, was associated with sexual infidelity.
      Individuals who had (versus had not) previously engaged in infidelity reported
      more unrestricted sociosexuality, while reporting less commitment. For
      individuals reporting prior sexual infidelity, unrestricted sociosexual desire
      and lesser commitment were associated with more permissive perceptions of
      infidelity. For individuals reporting no prior sexual infidelity, greater
      commitment was always associated with more strict perceptions of infidelity. No
      gender differences emerged in the analyses. Also, no differences were found
      according to individual motivations (i.e., looking to know other people versus
      seeking casual sex) or relational motivations (i.e., individual registration
      versus registration as a couple) underlying individuals' registration on the Web
      site. These results are an important addition to the literature on infidelity by
      analyzing a specific sample motivated to engage in infidelity. Implications for
      future research are discussed.

PMID- 27049475
TI  - More than just a problem with faces: altered body perception in a group of
      congenital prosopagnosics.
AB  - It has been estimated that one out of 40 people in the general population suffer
      from congenital prosopagnosia (CP), a neurodevelopmental disorder characterized
      by difficulty identifying people by their faces. CP involves impairment in
      recognizing faces, although the perception of non-face stimuli may also be
      impaired. Given that social interaction depends not only on face processing, but
      also on the processing of bodies, it is of theoretical importance to ascertain
      whether CP is also characterized by body perception impairments. Here, we tested
      11 CPs and 11 matched control participants on the Body Identity Recognition Task
      (BIRT), a forced-choice match-to-sample task, using stimuli that require
      processing of body-specific, not clothing-specific, features. Results indicated
      that the group of CPs were as accurate as controls on the BIRT, which is in line
      with the lack of body perception complaints by CPs. However, the CPs were slower
      than controls, and when accuracy and response times were combined into inverse
      efficiency scores (IESs), the group of CPs were impaired, suggesting that the CPs
      could be using more effortful cognitive mechanisms to be as accurate as controls.
      In conclusion, our findings demonstrate that CP may not generally be limited to
      face processing difficulties, but may also extend to body perception.

PMID- 27049476
TI  - Neuropsychological performance measures as intermediate phenotypes for attention
      deficit/hyperactivity disorder: A multiple mediation analysis.
AB  - Genetic influences on dopaminergic neurotransmission have been implicated in
      attention-deficit hyperactivity disorder (ADHD) and are theorized to impact
      cognitive functioning via alterations in frontal-striatal circuitry.
      Neuropsychological functioning has been proposed to account for the potential
      associations between dopamine candidate genes and ADHD. However, to date, this
      mediation hypothesis has not been directly tested. Participants were 498 youth
      ages 6-17 years (mean M = 10.8 years, SD = 2.4 years, 55.0% male). All youth
      completed a multistage, multiple-informant assessment procedure to identify ADHD
      and non-ADHD cases, as well as a comprehensive neuropsychological battery. Youth
      provided a saliva sample for DNA analyses; the 480 base pair variable number of
      tandem repeat polymorphism of the dopamine active transporter 1 gene (DAT1) and
      the 120 base pair promoter polymorphism of the dopamine receptor D4 gene (DRD4)
      were genotyped. Multiple mediation analysis revealed significant indirect
      associations between DAT1 genotype and inattention, hyperactivity-impulsivity,
      and oppositionality, with specific indirect effects through response inhibition.
      The results highlight the role of neurocognitive task performance, particularly
      response inhibition, as a potential intermediate phenotype for ADHD, further
      elucidating the relationship between genetic polymorphisms and externalizing
      psychopathology.

PMID- 27049477
TI  - Plasma Copeptin, AVP Gene Variants, and Incidence of Type 2 Diabetes in a Cohort
      From the Community.
AB  - CONTEXT: Experimental data support a role for vasopressin in metabolic disorders.
      OBJECTIVE: We investigated associations of plasma copeptin, a surrogate of
      vasopressin, and of allelic variations in the arginine vasopressin-neurophysin II
      gene with insulin secretion, insulin sensitivity, and the risk for impaired
      fasting glucose (IFG) and type 2 diabetes mellitus (T2DM). DESIGN, SETTING, AND
      PARTICIPANTS: We studied 5110 unrelated French men and women from a prospective
      cohort of the general population (Data from Epidemiological Study on the Insulin
      Resistance Syndrome cohort, 9-y follow-up). Six single nucleotide polymorphisms
      were genotyped. MAIN OUTCOME MEASURE: Incidence of IFG or T2DM during follow-up.
      RESULTS: The incidence of hyperglycemia (IFG/T2DM) during follow-up by quartiles
      of baseline plasma copeptin was 11.0% (Q1), 14.5% (Q2), 17.0% (Q3), and 23.5%
      (Q4), log-rank test P = .003. Participants in the upper quartile of plasma
      copeptin had significantly lower insulin sensitivity (homeostasis model
      assessment index) at baseline and during follow-up, as compared with other
      participants. Cox proportional hazards regression analyses showed significant
      associations of the CC genotype of rs6084264, the TT genotype of rs2282018, the C
      allele of rs2770381, and the CC genotype of rs1410713 with the incidence of
      hyperglycemia. The genotypes associated with an increased risk of hyperglycemia
      were also associated with increased plasma copeptin in men but not in women.
      CONCLUSIONS: High plasma copeptin was associated with reduced insulin sensitivity
      and an increased risk for IFG/T2DM diabetes in this community-based cohort.
      Moreover, in men, allelic associations support a causal role for vasopressin in
      these disorders.

PMID- 27049478
TI  - A mechanistic PK/PD model for two anti-IL13 antibodies explains the difference in
      total IL-13 accumulation observed in clinical studies.
AB  - IMA-638 and IMA-026 are humanized IgG1 monoclonal antibodies (mAbs) that target
      non-overlapping epitopes of IL-13. Separate first-in-human single ascending dose
      studies were conducted for each mAb. These studies had similar study designs, but
      mild to moderate asthmatics were recruited for the IMA-638 study and healthy
      subjects were recruited for the IMA-026 study. IMA-638 and IMA-026 showed similar
      pharmacokinetic (PK) profiles, but very different total IL-13 (free and drug
      bound IL-13) profiles; free IL13 was not measured. IMA-026 treatment induced a
      dose-dependent accumulation of total IL-13, while IMA-638 treatment led to a much
      smaller accumulation without any clear dose-response. To understand the
      differences between the two total IL-13 profiles and to predict the free IL-13
      profiles for each mAb treatment, a mechanistic PK/pharmacodynamic model was
      developed. PK-related parameters were first fit to the mean PK profiles of each
      mAb separately; thereafter, the target-related parameters were fit to both total
      IL-13 profiles simultaneously. The IL-13 degradation rate was assumed to be the
      same for asthma patients and healthy subjects. The model suggests that an
      approximately 100* faster elimination of IL-13-IMA-638 complex than IL-13-IMA-026
      complex could be responsible for the differences observed in total IL-13 profiles
      for the two mAbs. Furthermore, the model predicts that IMA-638 administration
      results in greater and more prolonged free IL-13 inhibition than equivalent
      dosing of IMA-026 despite similar binding KD and PK profile. In conclusion, joint
      modeling of two similar molecules provided mechanistic insight that the
      elimination rate of mAb-target complex can regulate the degree of free target
      inhibition.

PMID- 27049479
TI  - Translation and validation of the assistive technology device predisposition
      assessment in Greek in order to assess satisfaction with use of the selected
      assistive device.
AB  - PURPOSE: To examine the Assistive Technology Device Predisposition Assessment
      scale and provide evidence of validity and reliability of the Greek version.
      METHODS: We translated and adapted the original instrument in Greek according to
      the most well-known guidelines recommendations. Field test studies were conducted
      in a rehabilitation hospital to validate the appropriateness of the final
      results. Ratings of the different items were statistically analyzed. We recruited
      115 subjects who were administered the Form E of the original questionnaire.
      RESULTS: The experimental analysis conducted revealed a three subscales
      structure: (i) Adaptability, (ii) Fit to Use, and (iii) Socializing. According to
      the results of our study the three subscales measure different constructs.
      Reliability measures (ICC = 0.981, Pearson's correlation = 0.963, Cronbach's
      alpha = 0.701) yielded high values. Test-retest outcome showed great stability.
      CONCLUSIONS: This is the first study, at least to the knowledge of the authors,
      which focuses merely on measuring the satisfaction of the users from the used
      assistive device, while exploring the Assistive Technology Device Predisposition
      Assessment - Device Form in such depth. According to the results, it is a stable,
      valid and reliable instrument and applicable to the Greek population. Thus, it
      can be used to measure the satisfaction of patients with assistive devices.
      Implications for Rehabilitation The paper explores the cultural adaptability and
      applicability of ATD PA - Device Form. ATD PA - Device Form can be used to assess
      user satisfaction by the selected assistive device. ATD PA - Device Form is a
      valid and reliable instrument in measuring users' satisfaction in Greekreality.

PMID- 27049480
TI  - Impact of a prenatally diagnosed nuchal cord on obstetrical outcome in an
      unselected population.
AB  - OBJECTIVE: Evaluate the outcome of prenatally diagnosed nuchal cord. METHODS: A
      retrospective study on all cases of prenatally diagnosed nuchal cord. Study end
      points were gestational age at delivery, intrapartum fetal heart rate (FHR)
      abnormalities, mode of delivery, intrauterine fetal growth retardation (IUGR),
      intrauterine fetal demise (IUFD), and the rate of labor induction. RESULTS: This
      study included 44 cases; 86% were diagnosed at second trimester scan, confirmed
      by Color Doppler and 3D ultrasound. Mean gestational age at delivery was 39
      weeks.18/44 cases (41%) underwent labor induction mostly as a result of parental
      anxiety. Primary cesarean rate was 34% (15/44), and 16% (7/44) had intrapartum
      FHR abnormalities with no impact for induction of labor. Instrumental vaginal
      delivery was used in 5 cases. IUGR was present in 7% (3/44), and none had IUFD.
      Nuchal cord was confirmed at birth in all cases. Correct prenatal diagnosis was
      in only one case of the 5/44 (11%) with multiple loops. CONCLUSION: Prenatal
      diagnosis of nuchal cord is feasible with difficulty in determining multiple
      loops. Outcome is favorable, but parental anxiety is common and may increase
      induction rates, without leading to difference in cesarean rates or FHR
      abnormalities.

PMID- 27049481
TI  - Greek cultural adaption and validation of the Kujala anterior knee pain scale in
      patients with patellofemoral pain syndrome.
AB  - PURPOSE: To cross-culturally adapt and validate the Greek version of the Kujala
      anterior knee pain scale (KAKPS). METHODS: The Greek KAKPS was translated from
      the original English version following standard forward and backward translation
      procedures. The survey was then conducted in clinical settings by a questionnaire
      comprising the Greek KAKPS and patellofemoral pain syndrome (PFPS) severity
      scale. A total of 130 (62 women and 68 men) Greek-reading patients between 18 and
      45 years old with anterior knee pain (AKP) for at least four weeks were recruited
      from physical therapy clinics. To establish test-retest reliability, the patients
      were asked to complete the KAKPS at initial visit and 2-3 days after the initial
      visit. The Greek version of the PFPS severity scale was also administered once at
      initial visit. Internal consistency of the translated instrument was measured
      using Cronbach's alpha. An intraclass correlation coefficient was used to assess
      the test-retest reliability of the KAKPS. Concurrent validity was measured by
      correlating the KAKPS with the PFPS severity scale using Pearson's correlation
      coefficient. RESULTS: The results showed that the Greek KAKPS has good internal
      consistency (Cronbach's alpha = 0.942), test-retest reliability (ICC = 0.921) and
      concurrent validity (r > 0.7). CONCLUSIONS: This study has shown that the Greek
      KAKPS has good internal consistency, test-retest reliability and concurrent
      validity when correlated with the PFPS severity scale in adult patients with AKP
      for at least four weeks. Implications for rehabilitation The Greek version of the
      KAKPS has been found to be reliable and valid when used in adult patients with
      AKP for at least four weeks. The results of the psychometric characteristics were
      compatible with those of the original English version. The KAKPS could be applied
      in a Greek-speaking population to assess functional limitations and symptoms in
      patients aged 18-45 years old with AKP for at least four weeks.

PMID- 27049482
TI  - Spin-wave instabilities of ferromagnetic nanowire stripes under parallel pumping.
AB  - A microscopic (or Hamiltonian-based) theory is presented for the spin-wave
      instability thresholds in ferromagnetic nanowires under conditions of parallel
      pumping with a microwave field. A dipole-exchange Hamiltonian is employed in
      which the external magnetic field is either longitudinal or transverse to the
      length of the nanowire. This contrasts with most previous work on nonlinear spin
      waves which concentrate on situations where a macroscopic (or continuum) theory
      is appropriate. In nanowire stripes with lateral dimensions of order 100 nm or
      less, the quantization of the eigenmodes becomes modified due to strong spatial
      confinement and edge effects, making it appropriate to employ a microscopic
      dipole-exchange approach analogous to that used recently for ultrathin films.
      Numerical applications are presented for the dependence of the threshold
      microwave field amplitude for instability on the static applied field (the analog
      of the butterfly curves). The cases of longitudinal and transverse applied fields
      are found to lead to distinctly different behaviors, which are illustrated using
      EuS and permalloy as materials with different ratios of dipolar to exchange
      interactions. Structural effects due to the discrete spin-wave branches lead to
      structural aspects of the butterfly curves that are significantly modified
      compared with those for ultrathin films due to the edge modes in the nanowires. 

PMID- 27049484
TI  - Angiogenesis and portal-systemic collaterals in portal hypertension.
AB  - In patients with advanced liver disease with portal hypertension, portal-systemic
      collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage,
      hepatic encephalopathy, ascites, hepatopulmonary syndrome and portopulmonary
      hypertension. Angiogenesis has a pivotal role in the formation of portal-systemic
      shunts. Recent research has defined many of the mediators and mechanisms involved
      in this angiogenic process, linking the central roles of hepatic stellate cells
      and endothelial cells. Studies of animal models have demonstrated the potential
      therapeutic impact of drugs to inhibit angiogenesis in cirrhosis. For example,
      inhibition of VEGF reduces portal pressure, hyperdynamic splanchnic circulation,
      portosystemic collateralization and liver fibrosis. An improved understanding of
      the role of other angiogenic factors provides hope for a novel targeted therapy
      for portal hypertension with a tolerable adverse effect profile.

PMID- 27049485
TI  - Management of gastroesophageal varices in cirrhotic patients: current status and
      future directions.
AB  - Bleeding from gastroesophageal varices (GEV) is a serious event in cirrhotic
      patients and can cause death. According to the explosion theory, progressive
      portal hypertension is the primary mechanism underlying variceal bleeding. There
      are two approaches for treating GEV: primary prophylaxis to manage bleeding or
      emergency treatment for bleeding followed by secondary prophylaxis. Treatment
      methods can be classified into two categories: 1) Those used to decrease portal
      pressure, such as medication (i.e., nonselective beta-blockers), radiological
      intervention [transjugular intrahepatic portosystemic shunt (TIPS)] or a surgical
      approach (i.e., portacaval shunt), and 2) Those used to obstruct GEV, such as
      endoscopy [endoscopic variceal ligation (EVL), endoscopic injection sclerotherapy
      (EIS), and tissue adhesive injection] or radiological intervention [balloon
      occluded retrograde transvenous obliteration (BRTO)]. Clinicians should choose a
      treatment method based on an understanding of its efficacy and limitations.
      Furthermore, elastography techniques and serum biomarkers are noninvasive methods
      for estimating portal pressure and may be helpful in managing GEV. The impact of
      these advances in cirrhosis therapy should be evaluated for their effectiveness
      in treating GEV.

PMID- 27049486
TI  - Utility and limitations of APRI and FIB4 to predict staging in a cohort of
      nonselected outpatients with hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C(CHC) staging is important for therapeutic
      decision-making. Identification of noninvasive markers can provide alternatives
      to liver biopsy. AIM: To assess the value of APRI and FIB4 for CHC fibrosis
      staging in a cohort of nonselected outpatients from a referral center in Sao
      Paulo, Brazil. MATERIAL AND METHODS: Medical records of 798 adult outpatients
      were analyzed retrospectively. For calculations of APRI and FIB4, the original
      descriptions were considered, and markers were compared with degree of liver
      injury. RESULTS: Overall, 49.3% of participants were female, and mean age was
      56.9 +/- 12.5 years. Genotype 1 was predominant (71.7 vs. 23.7% genotype 3); 64%
      had significant fibrosis, 44% had advanced fibrosis, and 28% had cirrhosis. The
      areas under the receiver operating curve for significant fibrosis, advanced
      fibrosis, and cirrhosis, respectively, were 0.809, 0.819, and 0.815 for the APRI
      marker and 0.803, 0.836 and 0.852 for FIB4. Using the recommended cut off values,
      approximately 30-40% of the patients could not be classified. In the remainder,
      either APRI or FIB4 alone correctly diagnosed 80-85% of cases. Concomitant or
      consecutive use of both APRI and FIB4 increased the number of the cases correctly
      diagnosed only slightly, but also increased the number of patients not classified
      within the cutoff values. CONCLUSIONS: In conclusion, use of the APRI or FIB4
      markers for detection of hepatic fibrosis may be a viable alternative at referral
      centers for treatment of CHC in low- and middle-income countries. Despite
      relatively good accuracy, a significant number of patients could not be assessed
      by these methods.

PMID- 27049488
TI  - Nonalcoholic steatohepatitis in morbid obese patients: coffee consumption vs.
      disease severity.
AB  - INTRODUCTION: Obesity correlates with nonalcoholic fatty liver disease (NAFLD)
      and occurs in 90 to 100% of severely obese individuals (body mass index [BMI] >
      35 kg/m2). Coffee consumption (CC) has been associated with reduced progression
      of fibrosis in both hepatitis C infection and NAFLD; however, this topic is still
      under discussion when this liver disease affects severely obese individuals.
      OBJECTIVE: To assess the association between CC, insulin resistance (IR) and
      histological NAFLD morbid obese patients. MATERIAL AND METHODS: Cross-sectional
      study, including obese individuals undergoing bariatric surgery, liver biopsy and
      histological diagnosis between September 2013 and August 2014. The patients were
      classified into 3 groups according to their weekly CC: 0- 239.9 mL; 240-2099.9 mL
      and >= 2100 mL. RESULTS: A total of 112 obese individuals were included (BMI =
      41.9 +/- 4.3 kg/m2), with a mean age of 34.7 +/- 7.4 years; 68.6% were women. CC
      was reported by 72.3% of patients. There were no statistical significant
      differences between groups regarding the presence of IR (84.8% vs. 74.2% vs.
      75.9%; p = 0.536). Progressively higher percentages of individuals with normal
      liver histology were observed (14.7% vs. 21.9% vs. 24.3%). NASH (65.7% vs. 70.3%
      vs. 57.5%) were observed among those who consumed greater coffee volumes (p =
      0.812). In conclusion, obese individuals with elevated CC exhibited lower
      frequencies of NASH, although with no statistical significance in this sample.

PMID- 27049487
TI  - Faldaprevir, pegylated interferon, and ribavirin for treatment-naive HCV genotype
      1: pooled analysis of two phase 3 trials.
AB  - INTRODUCTION & AIM: Faldaprevir is a potent once-daily (q.d.) hepatitis C virus
      (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies
      evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in
      treatment-naive patients with chronic HCV genotype-1 infection. MATERIAL AND
      METHODS: Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg
      q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV
      (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required
      early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week
      8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24.
      Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12).
      RESULTS: SVR12 rates were significantly higher for patients treated with
      faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo
      (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype)
      faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95%
      CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates
      for patients receiving faldaprevir compared with placebo. The incidence of
      adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and
      slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%,
      7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg
      groups, respectively. CONCLUSION: Addition of faldaprevir to PegIFN/RBV increased
      SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg
      is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888
      and NCT01297270.

PMID- 27049489
TI  - Predictors and impacts of hospital readmissions following liver transplantation.
AB  - While liver transplantation is the definitive therapy for end stage liver
      disease, it remains a major procedure, with many potential complications.
      Hospital readmissions after the initial hospitalization for liver transplantation
      can be associated with adverse outcomes, increased cost, and resource
      utilization. Our aim was to define the incidence and reasons for hospital
      readmission after liver transplant and the impact of readmissions on patient
      outcomes. We retrospectively analyzed 30- and 90-day readmission rates and
      indications in patients who underwent liver transplant at a large-volume
      transplant center over a 3-year period. Four hundred seventy-nine adult patients
      underwent their first liver transplant during the study period. The 30-day
      readmission rate was 29.6%. Recipient and donor age, etiology of liver disease,
      biological Model for End-Stage Liver Disease score, and cold ischemia time were
      similar between patients who were readmitted within 30 days and those who were
      not readmitted. Readmissions occurred in 25% of patients who were hospitalized
      prior to liver transplant compared to 30% who were admitted for liver transplant.
      The most common indications for readmission were infection, severe abdominal
      pain, and biliary complications. Early discharge from hospital (fewer than 7 days
      after liver transplant), was not associated with readmission; however, a
      prolonged hospital stay after liver transplant was associated with an increased
      risk of readmission (p = 0.04). In conclusion, patients who undergo liver
      transplant have a high rate of readmission. In our cohort, readmissions were
      unrelated to pre-existing recipient or donor factors, but were associated with a
      longer hospital stay after liver transplant.

PMID- 27049491
TI  - Cultural validation of the post-Liver transplant quality of life (pLTQ)
      questionnaire for the Brazilian population.
AB  - BACKGROUND AND RATIONALE: The post-Liver Transplant Quality of Life (pLTQ)
      questionnaire, developed in the United States, is a disease-targeted instrument
      designed to evaluate health-related quality of life (HRQoL) in liver transplant
      recipients. Our study sought to validate a version of the pLTQ for use in the
      Brazilian population. Translation and cross-cultural adaptation were carried out
      in accordance with international standard practices for questionnaire validation.
      Validity was measured by means of convergent validity (correlations between pLTQ
      domains and WHOQOL-Bref domains). Reliability was assessed by measurement of
      internal consistency (Cronbach's alpha coefficient), reproducibility (intraclass
      correlation coefficient), sensitivity to change (effect size), and floor and
      ceiling effects. RESULTS: The study sample comprised 160 liver transplant
      recipients, with a mean age of 56.9 +/- 10.4 years, treated at a tertiary
      hospital in Southern Brazil. The sample was largely male (62.5%), and the
      predominant indication for liver transplant was hepatocellular carcinoma (49.4%).
      Only two questionnaire items were modified during the translation and cross
      cultural validation stage. The mean total pLTQ score was 5.58 +/- 0.9, with < 20%
      floor/ceiling effect. Correlations between pLTQ and WHOQOL-Bref domains were
      acceptable (r = 0.37-0.40). For similar dimensions, the correlations between
      WHOQOL-Bref and pLTQ were statistically significant (p <= 0.001). Cronbach's
      alpha for the total score was 0.91 (95% CI 0.89-0.93), with a range of 0.51 to
      0.77 across domains. Reproducibility was 0.90, and sensitivity to change was
      0.84. CONCLUSION: In conclusion, the Brazilian Portuguese version of the pLTQ
      exhibited good psychometric performance, suggesting that it can be a useful tool
      in the Brazilian cultural context.

PMID- 27049490
TI  - Diagnostic accuracy of magnetic resonance elastography in liver transplant
      recipients: A pooled analysis.
AB  - BACKGROUND AND AIMS: We conducted an individual participant data (IPD) pooled
      analysis on the diagnostic accuracy of magnetic resonance elastography (MRE) to
      detect fibrosis stage in liver transplant recipients. MATERIAL AND METHODS:
      Through a systematic literature search, we identified studies on diagnostic
      performance of MRE for staging liver fibrosis, using liver biopsy as gold
      standard. We contacted study authors for published and unpublished IPD on age,
      sex, body mass index, liver stiffness, fibrosis stage, degree of inflammation and
      interval between MRE and biopsy; from these we limited analysis to patients who
      had undergone liver transplantation. Through pooled analysis using nonparametric
      two-stage receiver-operating curve (ROC) regression models, we calculated the
      cluster-adjusted AUROC, sensitivity and specificity of MRE for any (>= stage 1),
      significant (>= stage 2) and advanced fibrosis (>= stage 3) and cirrhosis (stage
      4). RESULTS: We included 6 cohorts (4 published and 2 unpublished series)
      reporting on 141 liver transplant recipients (mean age, 57 years; 75.2% male;
      mean BMI, 27.1 kg/m2). Fibrosis stage distribution stage 0, 1, 2, 3, or 4, was
      37.6%, 23.4%, 24.8%, 12% and 2.2%, respectively. Mean AUROC values (and 95%
      confidence intervals) for diagnosis of any (>= stage 1), significant (>= stage
      2), or advanced fibrosis (>= stage 3) and cirrhosis were 0.73 (0.66-0.81), 0.69
      (0.62-0.74), 0.83 (0.61-0.88) and 0.96 (0.93-0.98), respectively. Similar
      diagnostic performance was observed in stratified analysis based on sex, obesity
      and inflammation grade. CONCLUSIONS: In conclusion, MRE has high diagnostic
      accuracy for detection of advanced fibrosis and cirrhosis in liver transplant
      recipients, independent of BMI and degree of inflammation.

PMID- 27049492
TI  - Cytokeratin19 positive hepatocellular carcinoma is associated with increased
      peritumoral ductular reaction.
AB  - BACKGROUND AND AIMS: Cytokeratin19 positive (CK19+) hepatocellular carcinoma
      (HCC) is thought to derive from liver progenitor cells (LPC). However, whether
      peritumoralductular reaction (DR) differs between CK19+ and CK19 negative (CK19-)
      HCC patients remains unclear. MATERIAL AND METHODS: One hundred and twenty HBV
      related HCC patients were enrolled in this study. Clinicopathological variables
      were collected, and immunohistochemistry staining for CK19, proliferating cell
      nuclear antigen (PCNA), interleukin-6 (IL-6) and beta-catenin were performed in
      tumor and peritumor liver tissues. RESULTS: CK19+ HCC patients had higher grade
      of peritumoral DR and proportion of proliferative DR than the CK19- group. The
      mean number or the proportion of cytoplasmic beta-catenin+ DR was higher in the
      CK19+ group than in the CK19- group. Furthermore, there were more patients with
      nuclear beta-catenin+ peritumoral DR in the CK19+ group as compared to the CK19-
      group. CONCLUSION: Peritumoral DR was more abundant and proliferative in CK19+
      HCC patients, with higher level of nuclear translocation of beta-catenin.
      However, it is unclear whether peritumoral DR is the cause or result of poor
      prognosis in these patients.

PMID- 27049493
TI  - Small bowel capsule endoscopy and portal hypertensive enteropathy in cirrhotic
      patients: results from a tertiary referral centre.
AB  - BACKGROUND AND RATIONALE: Portal hypertensive enteropathy (PHE) remains difficult
      to diagnose in patients with cirrhosis and portal hypertension. Limited test
      choices exist for the inspection of the small bowel in these patients. Small
      bowel capsule endoscopy (SBCE) is ideal in this situation but rarely performed.
      We aimed to determine the prevalence of PHE using SBCE in a cirrhotic patient
      population and correlate its presence with clinical and CT imaging findings.
      MATERIAL AND METHODS: We retrospectively analysed data from cirrhotic patients
      who underwent SBCE at our unit. Studies were evaluated for the presence of
      cirrhosis-related findings in the oesophagus, stomach and small-bowel. The
      relationships between PHE and patients' clinical characteristics were evaluated.
      RESULTS: 53 patients with cirrhosis underwent SCBE. We used PillCam(r)SB on 36
      patients and MiroCam(r) capsule on 17. Thirty patients were referred for iron
      deficiency anaemia, 15 for obscure gastrointestinal bleeding, and 4 for other
      indications. Four data sets were not available for review, leaving 49 patients.
      Mean age was 61.19 +/- 14.54 years (M/F = 27/22). Six SBCE examinations were
      incomplete. Thirty three patients had evidence of portal hypertensive gastropathy
      (PHG) and 17 had evidence of oesophageal varices. In total, 29 patients had SCBE
      evidence of PHE (57%). 28/29 (96.5%) patients with PHE had also evidence of PHG.
      13/17 (76.4%) patients with oesophageal varices had also evidence of PHE.
      CONCLUSIONS: The prevalence of PHE in our study was 57%. SBCE is a useful tool in
      evaluating PHE in cirrhotic patients irrespective of aetiology.

PMID- 27049494
TI  - Is intestinal oxidative stress involved in patients with compensated liver
      cirrhosis?
AB  - BACKGROUND: Liver cirrhosis is associated with intestinal epithelial barrier
      dysfunction, which may be affected by oxidative stress. Studies in cirrhotic rats
      provided evidence for intestinal oxidative stress, but studies in cirrhotic
      patients are scarce. We have shown intestinal barrier dysfunction in patients
      with compensated cirrhosis. AIM: The present study aimed to investigate whether
      oxidative stress occurs in the intestinal mucosa of compensated cirrhotic
      patients and may contribute to barrier dysfunction. MATERIAL AND METHODS:
      Oxidative stress was studied in duodenal and sigmoid biopsies from 15 cirrhotic
      patients and 22 controls by analyzing transcription of genes involved in
      glutathione and uric acid metabolism using quantitative real-time polymerase
      chain reaction. Protein levels of glutathione and glutathione disulphide were
      measured and the glutathione/glutathione disulphide ratio was calculated as
      marker of oxidative stress. In addition, intestinal myeloperoxidase and fecal
      calprotectin were determined. RESULTS: Gene transcription of glutathione
      synthetase and glutathione reductase were significantly different in duodenal and
      sigmoid biopsies of cirrhotic patients vs. controls, but no alterations were
      found for other genes nor for glutathione, glutathione disulphide,
      glutathione/glutathione disulphide ratio and intestinal myeloperoxidase and fecal
      calprotectin concentrations. CONCLUSION: This study did not find indications for
      oxidative stress and low-grade inflammation in the small and large intestine of
      stable compensated cirrhotic patients. Although these preliminary findings need
      further validation, we found intestinal oxidative stress not to be a major
      mechanism contributing to epithelial barrier dysfunction in patients with
      compensated cirrhosis.

PMID- 27049495
TI  - Liver stiffness assessed by transient elastography in patients with beta
      thalassaemia major.
AB  - RATIONALE FOR THE STUDY: This cross-sectional multicenter study was conducted to
      investigate any difference in liver stiffness measurements (LSM), evaluated by
      transient elastography, between patients affected by beta thalassaemia major,
      with and without hepatitis C virus (HCV) infection, and healthy blood donors
      (controls). Secondary aim was to assess any correlation between transient
      elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or
      superconductive quantum interference device (SQUID) liver susceptometry values.
      MATERIALS AND METHODS: The study involved three centers. Transient elastography
      and MRI T2* examinations were performed in all centers. SQUID liver susceptometry
      was performed in center1 and center2. T-test for independent data or Mann-Whitney
      U test was used to analyse differences between two groups. Univariate Pearson's r
      coefficient was used to test correlations between liver stiffness measurements
      and all other variables. RESULTS: In a study with 119 patients and 183 controls,
      patients who had never been infected with HCV showed significantly higher LSMs
      than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p <
      0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for
      gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls
      (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver
      susceptometry values was observed. In conclusion, compared to controls beta
      thalassaemia major patients had a significant increase in LSMs independently from
      HCV infection.

PMID- 27049496
TI  - Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17
      and TGF-beta2 expression.
AB  - BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-beta1/2 are cytokines involved
      in the development of kidney, pulmonary and liver fibrosis. However, their
      expression kinetics in the pathogenesis of cholestatic liver fibrosis have not
      yet been fully explored. The aim of the study was to analyze the expression of IL
      17, RORgammat, NKp46, TGF-beta1, and TGF-beta2 in the liver of rats with bile
      duct ligation (BDL). RESULTS: Hepatic IL-17A gene expression analyzed by qRT-PCR
      showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL,
      respectively. TGFbeta1 and TGFbeta2 gene expression significantly increased
      throughout the whole fibrotic process. At the protein level in liver homogenates,
      IL-17, TGF-beta1, and RORgammat significantly increased at 8 and 30 days after
      BDL. Interestingly, a significant increase in the protein levels of TGF-beta2 and
      decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-beta2
      exhibited stronger signals than TGF-beta1 at the gene expression and protein
      levels. Histological analysis showed bile duct proliferation and collagen
      deposition. CONCLUSIONS: Our results suggest that pro-fibrogenic cytokines IL-17,
      TGF-beta1 and, strikingly, TGF-beta2 might be important players of liver damage
      in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17
      cells might represent an important source of IL-17, while NK cell depletion may
      account for the perpetuation of liver damage in the BDL model.

PMID- 27049497
TI  - Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine
      model of acute liver failure.
AB  - BACKGROUND: Pulmonary complications are common in acute liver failure (ALF). The
      role of the lungs in the uptake of harmful soluble endogenous macromolecules was
      evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8)
      vs. controls (n = 8). In additional experiments, pulmonary uptake was
      investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was
      applied to investigate the cellular uptake. RESULTS: As compared to controls, the
      ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold
      net increased uptake of both tissue plasminogen activator and lysosomal enzymes.
      Anatomical distribution experiments in healthy animals revealed that radiolabeled
      MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and
      24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the
      blood. Both fluorescence and electron microscopy revealed initial uptake of MA by
      pulmonary endothelial cells (PECs) with later translocation to pulmonary
      intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10
      min after injection. Systemic inflammatory markers such as leukopenia and
      increased serum TNF-alpha levels were evident after 20 min in the MA and LPS
      groups. CONCLUSION: Significant lung uptake of harmful soluble macromolecules
      compensated for the defect liver scavenger function in the ALF-group. Infusion of
      MA induced increased TNF-alpha serum levels and leukopenia, similar to the effect
      of the known inflammatory mediator LPS. These observations suggest a potential
      mechanism that may contribute to lung damage secondary to liver disease.

PMID- 27049498
TI  - Primary hepatic perivascular epithelioid tumor (PEComa).

PMID- 27049499
TI  - Autochthonous infection with hepatitis E virus related to subtype 3a, France: a
      case report.
AB  - Hepatitis E virus (HEV) recently emerged in Europe as a cause of autochthonous
      acute hepatitis and a porcine zoonosis. European autochthonous cases almost
      exclusively involved viruses of genotype 3, subtype 3a being only recently
      reported in France, from farm pigs. We report an autochthonous human infection
      with a HEV related to subtype 3a in Southeastern France. A 55-year-old human
      immunodeficiency virus-infected man presented liver cytolysis in June 2014. HEV
      RNA was detected in serum and three months later, anti-HEV IgM and IgG were
      positive whereas HEV RNA was no more detectable in serum. No biological or
      clinical complication did occur. HEV phylogeny based on two capsid gene fragments
      showed clustering of sequences obtained from the case-patient with HEV-3a, mean
      nucleotide identity being 91.7 and 91.3% with their 10 best GenBank matches that
      were obtained in Japan, South Korea, USA, Canada, Germany and Hungria from
      humans, pigs and a mongoose. Identity between HEV sequence obtained here and HEV
      3a sequences obtained at our laboratory from farm pigs sampled in 2012 in
      Southeastern France was only 90.2-91.4%. Apart from these pig sequences, best
      hits from France were of subtypes 3i, 3f, or undefined. The patient consumed
      barely cooked wild-boar meat; no other risk factor for HEV infection was
      documented. In Europe, HEV-3a has been described in humans in England and
      Portugal, in wild boars in Germany, and in pigs in Germany, the Netherlands, and,
      recently, France. These findings suggest to gain a better knowledge of HEV-3a
      circulation in France.

PMID- 27049500
TI  - Is ursodeoxycholic acid detrimental in obstructive cholestasis? A propos of a
      case of malignant biliary obstruction.
AB  - Ursodeoxycholic acid (UDCA) is the first choice medication for most cholestatic
      hepatopathies, due to its capability to counteract inflammation and bile-acid
      induced liver damage, two common features in cholestasis. However, UDCA is
      usually contraindicated in obstructive cholestasis, due to the alleged risk of
      biliary integrity disruption due to its choleretic effect. We report on an 83
      year-old man with an unsuspected malignant biliary obstruction who received
      moderate doses of UDCA (8-12 mg/kg/day) for 5 weeks, because the preliminary
      evidence suggested he had chemotherapy-induced cholestasis. Liver integrity was
      extensively protected by UDCA, as indicated by a marked decrease in serum liver
      enzymes, despite a steady increase in the levels of bilirubin and serum bile
      acids due to the obstructive process. In conclusion, this report shows, for the
      first time in humans, that moderate UDCA doses can reduce liver injury associated
      with complete biliary obstruction. This may contribute to a better understanding
      of the risk-benefit ratio of the use of UDCA in obstructive cholangiopathies.

PMID- 27049501
TI  - Rare biliary cystic tumors: a case series of biliary cystadenomas and
      cystadenocarcinoma.
AB  - Cystic lesions of the liver are common and a major proportion is formed by
      parasitic cysts and simple cysts. Biliary cystic tumors (BCTs), namely biliary
      cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC), are rare tumors which
      usually arise from the intrahepatic biliary tree. BCAs have malignant potential
      and are difficult to differentiate from BCAC pre-operatively on radiological
      imaging. Here we have presented 4 patients with BCTs and reviewed the literature
      pertaining to them.The data of four patients with BCA/BCAC diagnosed and treated
      at our institute were retrieved from our database and records were reviewed for
      age, sex, history, imaging, surgery, pathology and follow-up. Mean age of the
      patients was 53.5 years (range 30-71 years). Two male and two female patients
      presented with abdominal pain, of which one male patient had pancreatitis at
      diagnosis. Characteristic features were seen on pre-operative imaging (cystic
      lesions with internal septations) and biliary communication was identified in the
      patient with pancreatitis. Three patients were diagnosed with a BCA on final
      histology, while one patient had a BCAC. Following surgical resection, all the
      patients are asymptomatic and disease free with a mean follow-up of 24 months
      (range 10-40 months). In conclusion, BCTs should be suspected in the presence of
      a well-encapsulated, cystic hepatic lesion with internal septations. Although pre
      operative distinction between BCA and BCAC is difficult, the lesion, whenever
      possible, should be completely resected as long-term outcomes are good,
      especially with BCA.

PMID- 27049502
TI  - Bile acids and the Risk for Hepatocellular Carcinoma in Primary Biliary
      Cholangitis.

PMID- 27049505
TI  - Screening Recommendations for Hepatitis B Virus Infection.
AB  - CLINICAL QUESTION: What are the screening guidelines for hepatitis B virus (HBV)
      infection for asymptomatic, nonpregnant adolescents and adults in the United
      States? BOTTOM LINE: Patients with a high risk of infection, such as those with
      human immunodeficiency virus (HIV), who use injection drugs, or who live in a
      household where someone is infected with HBV; men who have sex with men; or
      patients who come from countries with a high prevalence of HBV infection, should
      be screened.

PMID- 27049506
TI  - Egocentric biases in comparative volume judgments of rooms.
AB  - The elongation of a figure or object can induce a perceptual bias regarding its
      area or volume estimation. This bias is notable in Piagetian experiments in which
      participants tend to consider elongated cylinders to contain more liquid than
      shorter cylinders of equal volume. We investigated whether similar perceptual
      biases could be found in volume judgments of surrounding indoor spaces and
      whether those judgments were viewpoint dependent. Participants compared a variety
      of computer-generated rectangular rooms with a square room in a psychophysical
      task. We found that the elongation bias in figures or objects was also present in
      volume comparison judgments of indoor spaces. Further, the direction of the bias
      (larger or smaller) depended on the observer's viewpoint. Similar results were
      obtained from a monoscopic computer display (Experiment 1) and stereoscopic head
      mounted display with head tracking (Experiment 2). We used generalized linear
      mixed-effect models to model participants' volume judgments using a function of
      room depth and width. A good fit to the data was found when applying weight on
      the depth relative to the width, suggesting that participants' judgments were
      biased by egocentric properties of the space. We discuss how biases in
      comparative volume judgments of rooms might reflect the use of simplified
      strategies, such as anchoring on one salient dimension of the space. 

PMID- 27049507
TI  - Which oral anticoagulant for atrial fibrillation.

PMID- 27049508
TI  - Buprenorphine buccal film (Belbuca) for chronic pain.

PMID- 27049509
TI  - Calcipotriene/betamethasone foam (Enstilar) for psoriasis.

PMID- 27049510
TI  - Dichlorphenamide (Keveyis) for periodic paralysis.

PMID- 27049512
TI  - Building up the pressure on chronic pain.

PMID- 27049511
TI  - Timing of Antiretroviral Treatment, Immunovirologic Status, and TB Risk:
      Implications for Testing and Treatment.
AB  - BACKGROUND: Tuberculosis (TB) risk and mortality increase in the 6 months after
      highly active antiretroviral therapy (HAART) initiation. This short-term risk may
      be a consequence of HAART initiation and immune reconstitution. Alternatively, it
      may be due to confounding by low CD4 counts and high HIV viral loads (VLs). We
      assessed the TB risk before and after HAART initiation while appropriately
      controlling for time-updated laboratory values and HAART exposure. METHODS: We
      conducted an observational cohort study among persons enrolled in the North
      American AIDS Cohort Collaboration on Research and Design from 1998 through 2011.
      A marginal structural model was constructed to estimate the association of HAART
      initiation and TB risk. Inverse probability weights for the probability of HAART
      initiation were incorporated. RESULTS: Among 26,342 patients, 94 cases of TB were
      diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates
      were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART
      initiation, 203/100,000 p-y (95% CI: 126 to 311) <=6 months after HAART
      initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After
      controlling for time-updated laboratory values, the adjusted odds of TB <=6
      months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and
      0.29 (95% CI: 0.16 to 0.53), respectively. CONCLUSIONS: TB risk in the first 6
      months after HAART initiation is not higher than that before HAART initiation
      after adjusting for CD4 count and VLs. These findings suggest that short-term TB
      risk may be related to low CD4 counts and high VLs near HAART initiation and
      support early HAART initiation to decrease TB risk.

PMID- 27049513
TI  - Nuclear Quantum Effects in Water and Aqueous Systems: Experiment, Theory, and
      Current Challenges.
AB  - Nuclear quantum effects influence the structure and dynamics of hydrogen-bonded
      systems, such as water, which impacts their observed properties with widely
      varying magnitudes. This review highlights the recent significant developments in
      the experiment, theory, and simulation of nuclear quantum effects in water. Novel
      experimental techniques, such as deep inelastic neutron scattering, now provide a
      detailed view of the role of nuclear quantum effects in water's properties. These
      have been combined with theoretical developments such as the introduction of the
      principle of competing quantum effects that allows the subtle interplay of
      water's quantum effects and their manifestation in experimental observables to be
      explained. We discuss how this principle has recently been used to explain the
      apparent dichotomy in water's isotope effects, which can range from very large to
      almost nonexistent depending on the property and conditions. We then review the
      latest major developments in simulation algorithms and theory that have enabled
      the efficient inclusion of nuclear quantum effects in molecular simulations,
      permitting their combination with on-the-fly evaluation of the potential energy
      surface using electronic structure theory. Finally, we identify current
      challenges and future opportunities in this area of research.

PMID- 27049515
TI  - Force exerted by a nanoscale capillary water bridge between two planar
      substrates.
AB  - Molecular dynamics simulation of a nanoscale capillary water bridge between two
      planar substrates is used to determine the resulting force between the substrates
      without arbitrariness regarding geometry and location of the free surface of the
      bridge. The substrates are moderately hydrophilic. The force changes continuously
      as the separation between the substrates changes except for small gaps where it
      becomes discontinuous because the bridge is unable to adopt stable configurations
      at any distance apart. Further exploration of the bridge and the force as the
      substrates approach each other reveals an underlying oscillatory force with an
      increasing repulsive component at separation distances equivalent to few water
      molecules. According to the average number of hydrogen bonds per water molecule
      (HBN), at very small gap sizes, water molecules which are very close to the
      surfaces are unable to maximize HBN thus contributing to the repulsive force. Our
      simulation results of force versus gap size agree with calculations based on
      other methods, some very different, and also reproduce the typical magnitude of
      the experimental force. Finally, a macroscopic force balance correctly describes
      the force-distance curve except for bridges constituted of water layers only. 

PMID- 27049514
TI  - Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.
AB  - Respiratory viruses cause asthma exacerbations. Because eosinophils are the
      prominent leukocytes in the airways of 60-70% of patients with asthma, we
      evaluated the effects of eosinophils on a common respiratory virus, parainfluenza
      1, in the lung. Eosinophils recruited to the airways of wild-type mice after
      ovalbumin sensitization and challenge significantly decreased parainfluenza virus
      RNA in the lungs 4 days after infection compared with nonsensitized animals. This
      antiviral effect was also seen in IL-5 transgenic mice with an abundance of
      airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice
      (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice
      (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase,
      using eosinophil peroxidase-deficient transgenic mice, did not reduce
      eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored
      in vitro. Isolated human eosinophils significantly reduced parainfluenza virus
      titers. This effect did not involve degradation of viral RNA by eosinophil
      granule RNases. However, eosinophils treated with a nitric oxide synthase
      inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral
      infectivity through production of nitric oxide. Consequently, eosinophil nitric
      oxide production was measured with an intracellular fluorescent probe.
      Eosinophils produced nitric oxide in response to virus and to a synthetic agonist
      of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNgamma
      increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide
      production. These results suggest that eosinophils promote viral clearance in the
      lung and contribute to innate immune responses against respiratory virus
      infections in humans.

PMID- 27049516
TI  - Vimentin fragments are potential markers of rheumatoid synovial fibroblasts.
AB  - OBJECTIVES: To study the protein expression differences between primary
      fibroblasts explanted from synovial membranes of patients with rheumatoid
      arthritis (RA) and osteoarthritis (OA). METHODS: Fibroblast cultures were
      obtained from 10 patients with RA and 5 patients with OA. After two-dimensional
      gel electrophoresis, proteins were excised and identified using peptide mass
      fingerprint. Expression of selected proteins was subsequently examined by
      immunoblot. Furthermore, we examined the cellular lysates for the presence of
      citrullinated proteins. RESULTS: The study was designed to compare expression
      changes of the common proteins detected in all studied fibroblast cultures (i.e.
      detected in all patients samples). We totally identified 191 shared proteins
      between RA and OA fibroblasts. A significant difference was defined as at least 2
      fold upregulation or 0.6-fold downregulation of protein expression. The most
      obvious alteration observed in RA was the appearance of several vimentin
      fragments not present in OA. We did not detect citrullinated proteins in lysates
      from RA fibroblasts. This corroborates the current assumption that fibroblasts
      are not able to citrullinate proteins by themselves and that invading macrophages
      play a central role in this process. CONCLUSIONS: We demonstrated that
      fibroblasts from patients with RA, despite being grown under identical
      conditions, preserve a particular feature and generate vimentin fragments not
      present in fibroblasts from OA. Elevated levels of different vimentin fragments
      have been recently reported in several rheumatic conditions. Further studies are
      needed to elucidate the pathogenic mechanisms induced by vimentin fragments in
      RA.

PMID- 27049517
TI  - On-surface synthesis of two-dimensional imine polymers with a tunable band gap: a
      combined STM, DFT and Monte Carlo investigation.
AB  - Two-dimensional polymers are of great interest for many potential applications in
      nanotechnology. The preparation of crystalline 2D polymers with a tunable band
      gap is critical for their applications in nano-electronics and optoelectronics.
      In this work, we try to tune the band gap of 2D imine polymers by expanding the
      conjugation of the backbone of aromatic diamines both laterally and
      longitudinally. STM characterization reveals that the regularity of the 2D
      polymers can be affected by the existence of lateral bulky groups. Density
      functional theory (DFT) simulations discovered a significant narrowing of the
      band gap of imine 2D polymers upon the expansion of the conjugation of the
      monomer backbone, which has been confirmed experimentally by UV absorption
      measurements. Monte Carlo simulations help us to gain further insight into the
      controlling factors of the formation of regular 2D polymers, which demonstrated
      that based on the all rigid assumption, the coexistence of different
      conformations of the imine moiety has a significant effect on the regularity of
      the imine 2D polymers. 

PMID- 27049518
TI  - Campylobacter fetus Subspecies Contain Conserved Type IV Secretion Systems on
      Multiple Genomic Islands and Plasmids.
AB  - The features contributing to differences in pathogenicity of the Campylobacter
      fetus subspecies are unknown. Putative factors involved in pathogenesis are
      located in genomic islands that encode a type IV secretion system (T4SS) and fic
      domain (filamentation induced by cyclic AMP) proteins, which may disrupt host
      cell processes. In the genomes of 27 C. fetus strains, three phylogenetically
      different T4SS-encoding regions (T4SSs) were identified: one was located in both
      the chromosome and in extra-chromosomal plasmids; one was located exclusively in
      the chromosome; and one exclusively in extra-chromosomal plasmids. We observed
      that C. fetus strains can contain multiple T4SSs and that homologous T4SSs can be
      present both in chromosomal genomic islands (GI) and on plasmids in the C. fetus
      strains. The GIs of the chromosomally located T4SS differed mainly by the
      presence of fic genes, insertion sequence elements and phage-related or
      hypothetical proteins. Comparative analysis showed that T4SS sequences, inserted
      in the same locations, were conserved in the studied C. fetus genomes. Using
      phylogenetic analysis of the T4SSs, it was shown that C. fetus may have acquired
      the T4SS regions from other Campylobacter species by horizontal gene transfer.
      The identified T4SSs and fic genes were found in Cff and Cfv strains, although
      the presence of T4SSs and fic genes were significantly associated with Cfv
      strains. The T4SSs and fic genes could not be associated with S-layer serotypes
      or geographical origin of the strains. 

PMID- 27049519
TI  - Discovering Karima (Euphorbiaceae), a New Crotonoid Genus from West Tropical
      Africa Long Hidden within Croton.
AB  - Croton scarciesii (Euphorbiaceae-Crotonoideae), a rheophytic shrub from West
      Africa, is shown to have been misplaced in Croton for 120 years, having none of
      the diagnostic characters of that genus, but rather a set of characters present
      in no known genus of the family. Pollen analysis shows that the new genus Karima
      belongs to the inaperturate crotonoid group. Analysis of a concatenated molecular
      dataset combining trnL-F and rbcL sequences positioned Karima as sister to
      Neoholstia from south eastern tropical Africa in a well-supported clade comprised
      of genera of subtribes Grosserineae and Neoboutonieae of the inaperturate
      crotonoid genera. Several morphological characters support the relationship of
      Karima with Neoholstia, yet separation is merited by numerous characters usually
      associated with generic rank in Euphorbiaceae. Quantitative ecological data and a
      conservation assessment supplement illustrations and descriptions of the taxon. 

PMID- 27049520
TI  - Genome-Wide Analysis and Characterization of Aux/IAA Family Genes in Brassica
      rapa.
AB  - Auxins are the key players in plant growth development involving leaf formation,
      phototropism, root, fruit and embryo development. Auxin/Indole-3-Acetic Acid
      (Aux/IAA) are early auxin response genes noted as transcriptional repressors in
      plant auxin signaling. However, many studies focus on Aux/ARF gene families and
      much less is known about the Aux/IAA gene family in Brassica rapa (B. rapa). Here
      we performed a comprehensive genome-wide analysis and identified 55 Aux/IAA genes
      in B. rapa using four conserved motifs of Aux/IAA family (PF02309). Chromosomal
      mapping of the B. rapa Aux/IAA (BrIAA) genes facilitated understanding cluster
      rearrangement of the crucifer building blocks in the genome. Phylogenetic
      analysis of BrIAA with Arabidopsis thaliana, Oryza sativa and Zea mays identified
      51 sister pairs including 15 same species (BrIAA-BrIAA) and 36 cross species
      (BrIAA-AtIAA) IAA genes. Among the 55 BrIAA genes, expression of 43 and 45 genes
      were verified using Genebank B. rapa ESTs and in home developed microarray data
      from mature leaves of Chiifu and RcBr lines. Despite their huge morphological
      difference, tissue specific expression analysis of BrIAA genes between the
      parental lines Chiifu and RcBr showed that the genes followed a similar pattern
      of expression during leaf development and a different pattern during bud, flower
      and siliqua development stages. The response of the BrIAA genes to abiotic and
      auxin stress at different time intervals revealed their involvement in stress
      response. Single Nucleotide Polymorphisms between IAA genes of reference genome
      Chiifu and RcBr were focused and identified. Our study examines the scope of
      conservation and divergence of Aux/IAA genes and their structures in B. rapa.
      Analyzing the expression and structural variation between two parental lines will
      significantly contribute to functional genomics of Brassica crops and we belive
      our study would provide a foundation in understanding the Aux/IAA genes in B.
      rapa.

PMID- 27049521
TI  - Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after
      Spinal Cord Injury.
AB  - Whether interlimb reflexes emerge only after a severe insult to the human spinal
      cord is controversial. Here the aim was to examine interlimb reflexes at rest in
      participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able
      bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering
      up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum
      of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately
      every 30 s). Participants were instructed to relax the test muscles prior to the
      delivery of the stimuli. Electromyographic activity was recorded bilaterally in
      proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation
      evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral
      leg muscles of SCI and control participants. Radial nerve stimulation evoked
      interlimb reflexes in the ipsilateral leg and contralateral arm muscles of
      control and SCI participants but only contralateral leg muscles of control
      participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation
      were longer in latency and duration, and larger in magnitude in SCI participants.
      Interlimb reflex properties were similar for both SCI and control groups for
      radial nerve stimulation. Ascending interlimb reflexes tended to occur with a
      higher incidence in participants with SCI, while descending interlimb reflexes
      occurred with a higher incidence in able-bodied participants. However, the
      overall incidence of interlimb reflexes in SCI and neurologically intact
      participants was similar which suggests that the neural circuitry underlying
      these reflexes does not necessarily develop after central nervous system injury. 

PMID- 27049522
TI  - Atomistic Simulation of Solubilization of Polycyclic Aromatic Hydrocarbons in a
      Sodium Dodecyl Sulfate Micelle.
AB  - Solubilization of two polycyclic aromatic hydrocarbons (PAHs), naphthalene (NAP,
      2-benzene-ring PAH) and pyrene (PYR, 4-benzene-ring PAH), into a sodium dodecyl
      sulfate (SDS) micelle was studied through all-atom molecular dynamics (MD)
      simulations. We find that NAP as well as PYR could move between the micelle shell
      and core regions, contributing to their distribution in both regions of the
      micelle at any PAH concentration. Moreover, both NAP and PYR prefer to stay in
      the micelle shell region, which may arise from the greater volume of the micelle
      shell, the formation of hydrogen bonds between NAP and water, and the larger
      molecular volume of PYR. The PAHs are able to form occasional clusters (from
      dimer to octamer) inside the micelle during the simulation time depending on the
      PAH concentration in the solubilization systems. Furthermore, the micelle
      properties (i.e., size, shape, micelle internal structure, alkyl chain
      conformation and orientation, and micelle internal dynamics) are found to be
      nearly unaffected by the solubilized PAHs, which is irrespective of the
      properties and concentrations of PAHs. 

PMID- 27049523
TI  - Tunable construction of multi-shelled hollow carbonate nanospheres and their
      potential applications.
AB  - The development of multi-shelled hollow carbonate nanospheres (MHCN) for
      biomedical applications is challenging, and has not been reported. In this study,
      a facile approach is firstly reported to synthesize hierarchically porous MHCN
      with controllable shell numbers using a novel strategy called layer-by-layer
      thermal decomposition of organic acid salts and templates. The choice of organic
      acid salts as the reactants is innovative and crucial. The shell numbers of
      porous MHCN can be easily controlled and tuned through adjusting the adsorption
      temperature of organic acid salts and/or the adsorption ability of the template.
      The synthetic method can not only open a window to prepare the multi-shelled
      carbonates but also provide a new strategy to synthesise other multi-shelled
      inorganic salts. Notably, the hierarchically porous multi-shelled hollow
      structures empower the carbonates with not only a large specific surface area but
      also good porosity and permeability, showing great potential for future
      applications. Herein, our in vitro/vivo evaluations show that CaCO3 MHCN possess
      a high drug loading capacity and a sustained-release drug profile. It is highly
      expected that this novel synthetic strategy for MHCN and novel MHCN platform have
      the potential for biomedical applications in the near future. 

PMID- 27049524
TI  - A Threshold-Minimization Scheme for Exploring the Energy Landscape of
      Biomolecules: Application to a Cyclic Peptide and a Disaccharide.
AB  - We present a scheme, called the threshold-minimization method, for globally
      exploring the energy landscapes of small systems of biomolecular interest where
      typical exploration moves always require a certain degree of subsequent
      structural relaxation in order to be efficient, e.g., systems containing small or
      large circular carbon chains such as cyclic peptides or carbohydrates. We show
      that using this threshold-minimization method we can not only reproduce the
      global minimum and relevant local minima but also overcome energetic barriers
      associated with different types of isomerism for the example of a cyclic peptide,
      cyclo-(Gly)4. We then apply the new method to the disaccharide alpha-d
      glucopyranose-1-2-beta-d-fructofuranose, report energetically preferred
      configurations and barriers to boat-chair isomerization in the glucopyranosyl
      ring, and discuss the energy landscape. 

PMID- 27049525
TI  - Searching for a Role of Nursing Personnel in Developing Landscape of Ehealth:
      Factors Determining Attitudes toward Key Patient Empowering Applications.
AB  - INTRODUCTION: Nurses may play an important role in the delivery of medical
      services based on the use of ehealth tools. Nevertheless, their taking an active
      role in an ehealth environment depends on their possessing the appropriate skills
      and mindset. The main objective of this paper was to assess nurses' opinions and
      to analyze the predictors of their acceptance of ehealth features relevant to
      patient empowerment with a strong focus on chronic care. METHODS: A survey was
      conducted among nurses from hospital centers of south-eastern Poland based on a
      questionnaire designed to assess their attitudes toward the ehealth domain. The
      predictors of the nurses' acceptance of ehealth usage within specific contexts
      were assessed with uni- and multivariate logistic regression. RESULTS: An
      analysis was performed on data from 648 questionnaires retained after a quality
      check. The duration of Internet use was consistently related to higher acceptance
      of ehealth applications and more certainty regarding the reliability of health
      related information available on the Internet. Nurses from urban medical centers
      were more skeptical about the use of specific ehealth solutions. CONCLUSION:
      Previous experience in using information technologies is the main factor
      influencing the acceptance of specific ehealth solutions relevant for care
      provided to patients suffering from chronic conditions.

PMID- 27049526
TI  - Serum 25-Hydroxyvitamin D Concentrations >=40 ng/ml Are Associated with >65%
      Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort
      Study.
AB  - BACKGROUND: Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been
      associated with a lower risk of multiple cancer types across a range of 25(OH)D
      concentrations. OBJECTIVES: To investigate whether the previously reported
      inverse association between 25(OH)D and cancer risk could be replicated, and if a
      25(OH)D response region could be identified among women aged 55 years and older
      across a broad range of 25(OH)D concentrations. METHODS: Data from two cohorts
      representing different median 25(OH)D concentrations were pooled to afford a
      broader range of 25(OH)D concentrations than either cohort alone: the Lappe
      cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30
      ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median
      25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9
      years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were
      developed and the association between 25(OH)D and cancer risk was examined with
      multivariate Cox regression using multiple 25(OH)D measurements and spline
      functions. The study included all invasive cancers excluding skin cancer.
      RESULTS: Age-adjusted cancer incidence across the combined cohort (N = 2,304) was
      840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe
      cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort).
      Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D
      concentrations >=40 ng/ml had a 67% lower risk of cancer than women with
      concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12-0.90). CONCLUSIONS: 25(OH)D
      concentrations >=40 ng/ml were associated with substantial reduction in risk of
      all invasive cancers combined.

PMID- 27049527
TI  - Validity of a Job-Exposure Matrix for Psychosocial Job Stressors: Results from
      the Household Income and Labour Dynamics in Australia Survey.
AB  - INTRODUCTION: A Job Exposure Matrix (JEM) for psychosocial job stressors allows
      assessment of these exposures at a population level. JEMs are particularly useful
      in situations when information on psychosocial job stressors were not collected
      individually and can help eliminate the biases that may be present in individual
      self-report accounts. This research paper describes the development of a JEM in
      the Australian context. METHODS: The Household Income Labour Dynamics in
      Australia (HILDA) survey was used to construct a JEM for job control, job demands
      and complexity, job insecurity, and fairness of pay. Population median values of
      these variables for all employed people (n = 20,428) were used to define
      individual exposures across the period 2001 to 2012. The JEM was calculated for
      the Australian and New Zealand Standard Classification of Occupations (ANZSCO) at
      the four-digit level, which represents 358 occupations. Both continuous and
      binary exposures to job stressors were calculated at the 4-digit level. We
      assessed concordance between the JEM-assigned and individually-reported exposures
      using the Kappa statistic, sensitivity and specificity assessments. We conducted
      regression analysis using mental health as an outcome measure. RESULTS: Kappa
      statistics indicate good agreement between individually-reported and JEM-assigned
      dichotomous measures for job demands and control, and moderate agreement for job
      insecurity and fairness of pay. Job control, job demands and security had the
      highest sensitivity, while specificity was relatively high for the four
      exposures. Regression analysis shows that most individually reported and JEM
      measures were significantly associated with mental health, and individually
      reported exposures produced much stronger effects on mental health than the JEM
      assigned exposures. DISCUSSION: These JEM-based estimates of stressors exposure
      provide a conservative proxy for individual-level data, and can be applied to a
      range of health and organisational outcomes.

PMID- 27049528
TI  - Poly(glycidyl methacrylate-co-2-hydroxyethyl methacrylate) Brushes as
      Peptide/Protein Microarray Substrate for Improving Protein Binding and
      Functionality.
AB  - We developed a three-dimensional (3D) polymer-brush substrate for protein and
      peptide microarray fabrication, and this substrate was facilely prepared by
      copolymerization of glycidyl methacrylate (GMA) and 2-hydroxyethyl methacrylate
      (HEMA) monomers via surface-initiated atom transfer radical polymerization (SI
      ATRP) on a glass slide. The performance of obtained poly(glycidyl methacrylate-co
      2-hydroxyethyl methacrylate) (P(GMA-HEMA)) brush substrate was assessed by
      binding of human IgG with rabbit antihuman IgG antibodies on a protein microarray
      and by the determination of matrix metalloproteinase (MMP) activities on a
      peptide microarray. The P(GMA-HEMA) brush substrate exhibited higher
      immobilization capacities for proteins and peptides than those of a two
      dimensional (2D) planar epoxy slide. Furthermore, the sensitivity of the P(GMA
      HEMA) brush-based microarray on rabbit antihuman IgG antibody detection was much
      higher than that of its 2D counterpart. The enzyme activities of MMPs were
      determined specifically with a low detection limit of 6.0 pg mL(-1) for MMP-2 and
      5.7 pg mL(-1) for MMP-9. By taking advantage of the biocompatibility of PHEMA,
      the P(GMA-HEMA) brush-based peptide microarray was also employed to evaluate the
      secretion of MMP-2 and MMP-9 by cells cultured off the chip or directly on the
      chip, and satisfactory results were obtained.

PMID- 27049529
TI  - Driver-passenger collaboration as a basis for human-machine interface design for
      vehicle navigation systems.
AB  - Human Factors concerns exist with vehicle navigation systems, particularly
      relating to the effects of current Human-Machine Interfaces (HMIs) on driver
      disengagement from the environment. A road study was conducted aiming to provide
      initial input for the development of intelligent HMIs for in-vehicle systems,
      using the traditional collaborative navigation relationship between the driver
      and passenger to inform future design. Sixteen drivers navigated a predefined
      route in the city of Coventry, UK with the assistance of an existing vehicle
      navigation system (SatNav), whereas a further 16 followed the navigational
      prompts of a passenger who had been trained along the same route. Results found
      that there were no significant differences in the number of navigational errors
      made on route for the two different methods. However, drivers utilising a
      collaborative navigation approach had significantly better landmark and route
      knowledge than their SatNav counterparts. Analysis of individual collaborative
      transcripts revealed the large individual differences in descriptor use by
      passengers and reference to environmental landmarks, illustrating the potential
      for the replacement of distance descriptors in vehicle navigation systems.
      Results are discussed in the context of future HMIs modelled on a collaborative
      navigation relationship. Practitioner Summary: Current navigation systems have
      been associated with driver environmental disengagement, this study uses an on
      road approach to look at how the driver-passenger collaborative relationship and
      dialogue can inform future navigation HMI design. Drivers navigating with
      passenger assistance demonstrated enhanced landmark and route knowledge over
      drivers navigating with a SatNav.

PMID- 27049530
TI  - 3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors.
AB  - Flavonoids are potential antibacterial agents. However, key substituents and
      mechanism for their antibacterial activity have not been fully investigated. The
      quantitative structure-activity relationship (QSAR) and molecular docking of
      flavonoids relating to potent anti-Escherichia coli agents were investigated.
      Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids.
      The cross-validated coefficient (q(2)) values for CoMFA (0.743) and for CoMSIA
      (0.708) were achieved, illustrating high predictive capabilities. Selected
      descriptors for the CoMFA model were ClogP (logarithm of the octanol/water
      partition coefficient), steric and electrostatic fields, while, ClogP,
      electrostatic and hydrogen bond donor fields were used for the CoMSIA model.
      Molecular docking results confirmed that half of the tested flavonoids inhibited
      DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a
      same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids
      changed their orientation, resulting in a decrease of inhibitory activity.
      Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4
      carbonyl groups were found to be crucial active substituents of flavonoids by
      interacting with key residues of GyrB, which were in agreement with the QSAR
      study results. These results provide valuable information for structure
      requirements of flavonoids as antibacterial agents. 

PMID- 27049531
TI  - Bone marrow metastasis of malignant melanoma in childhood arising within a
      congenital melanocytic nevus.
AB  - BACKGROUND: Malignant melanoma in childhood is infrequent and can arise within
      congenital melanocytic nevi. Spread of malignant melanoma to the bone marrow,
      especially in children, is extremely rare. METHODS AND RESULTS: Reported is a
      case of a 5-year-old boy with a congenital large melanocytic nevus of the head
      and neck who presented with a short history of low back and leg pain, fever and
      cervical lymphadenopathy. Despite regular follow-up by a dermatologist and
      plastic surgeon and repeatedly negative histology of previous partial excisions,
      diffuse bone marrow infiltration with malignant melanoma was diagnosed. The
      primary site was identified in the post-excision area. The disease progressed
      rapidly on ipilimumab immunotherapy and led to death at four months from the
      diagnosis. CONCLUSION: Surveillance is indispensable in children with a
      predisposition to melanoma and nonspecific symptoms such as bone pain, gait
      impairment or cytopenia, should always be taken into account.

PMID- 27049532
TI  - Systemic inflammatory response syndrome is reduced by preoperative plasma-thrombo
      leukocyte aphaeresis in a pig model of cardiopulmonary bypass.
AB  - OBJECTIVES: The systemic inflammatory response syndrome (SIRS) after cardiac
      surgery with cardiopulmonary bypass (CPB) exacerbates organ dysfunction and
      increases postoperative mortality. The aim of this study was to reduce SIRS after
      CPB in a pig model by profoundly decreasing all blood defence factors
      (complement, coagulation and fibrinolytic and contact systems, leukocytes and
      thrombocytes) using pre-operative aphaeresis. METHODS: Thirty-three pigs
      underwent 3 h of hypothermic CPB with 2 h of cardioplegic arrest, followed by 4
      days of observation. One half of the sample underwent prebypass plasma-thrombo
      leukocyte aphaeresis with the adjuvant leukofiltration. RESULTS: In the control
      group, there were classical signs of SIRS (tachycardia, tachypnea and
      leukocytosis) postoperatively. There was also myocardial ischaemia and the need
      for inotropic support in 90% of the control animals. Neutrophils showed an
      increase in superoxide anion production (P < 0.001), and surface neutral protease
      activity (P < 0.001) and blood endotoxin levels increased (P < 0.01) compared
      with preoperative levels. In contrast, in the aphaeretic group, there were no
      classical signs of SIRS; no myocardial ischaemia; minimum neutrophil production
      of the superoxide anion and protease activity were recorded (P < 0.001); and
      endotoxin levels were also decreased (P < 0.05) compared with the controls. In
      the control group, the haemodynamic problems associated with disconnecting from
      CPB correlated with the histologic findings in the myocardium (leukocyte
      endothelial adhesion and leukodiapedesis). CONCLUSIONS: Pre-operative plasma
      thrombo-leukocyte aphaeresis significantly reduces the major symptoms of SIRS and
      organ dysfunction after 3 h of CPB without adverse effects, such as bleeding and
      infection, during the postoperative course.

PMID- 27049533
TI  - High incidence of monozygotic twinning in infertility treatment.
AB  - BACKGROUND: Monozygotic twinning is associated with increased perinatal morbidity
      and mortality. There is evidence that the number of monozygotic twins increases
      after assisted reproductive techniques. METHODS: We searched PUBMED, MEDLINE, and
      Scopus from 1987 to 2015 for studies analyzing the incidence and possible
      etiology of monozygotic twinning in infertility patients and critically reviewed
      the current state of knowledge. RESULTS AND CONCLUSIONS: Monozygotic twinning is
      a rare in natural conception but occurs around twice the normal rate after
      assisted reproduction. Factors associated with this phenomenon remain
      speculative, though there is some evidence that micromanipulation techniques,
      prolonged culture, and genetics are involved. In view of the possible
      complications, adequate pre-conception counselling is advocated.

PMID- 27049534
TI  - Real-Time Specific Light-Up Sensing of Transferrin Receptor: Image-Guided
      Photodynamic Ablation of Cancer Cells through Controlled Cytomembrane
      Disintegration.
AB  - Transferrin receptor (TfR) represents a unique target for specific imaging of
      cancer cells and targeted delivery of therapeutic reagents. Detection and
      qualification of TfR is thus of great importance for cancer diagnosis and
      therapy. In this contribution, a light-up probe TPETH-2T7 was developed by
      conjugating a red-emissive photosensitizer with aggregation-induced emission
      (AIE) characteristics to a TfR-targeting peptide T7. The probe is almost
      nonemissive by itself, but it gives turn-on fluorescence in the presence of TfR
      with a detection limit of 0.45 MUg/mL. Cellular experiments show that the probe
      specifically binds to TfR-overexpressed cancer cells. Real-time imaging results
      reveal that the probe stains the MDA-MB-231 cell membrane in 30 min, which is
      followed by probe internalization. Experiments on image-guided photodynamic
      cancer ablation show that the therapeutic performance is better when TPETH-2T7 is
      localized on the cell membrane as compared to that being internalized into cells.
      Confocal laser scanning microscopy (CLSM) study reveals that cytomembrane
      disintegration allows quick ablation of MDA-MB-231 cells.

PMID- 27049535
TI  - Arsenic levels in the groundwater of Korea and the urinary excretion among
      contaminated area.
AB  - Drinking water is a main source of human exposure to arsenic. Hence, the
      determination of arsenic in groundwater is essential to assess its impact on
      public health. Here, we report arsenic levels in the groundwater of 722 sites
      covering all six major provinces of Korea. Water was sampled in two occasions
      (summer, 722 sites and winter, 636 sites) and the arsenic levels were measured
      with highly sensitive inductively coupled plasma-mass spectrometry method (limit
      of detection, 0.1 MUg/l) to encompass the current drinking water standard (<10
      MUg/l). Seasonal variation was negligible, but the geographical difference was
      prominent. Total arsenic in groundwater ranged from 0.1 to 48.4 MUg/l. A 88.0
      89.0% of sites were <2.0 MUg/l and the remaining ones generally did not exceed 10
      MUg/l (6.4-7.0%, 2.0-4.9 MUg/l; 2.4-3.0%, 5.0-9.9 MUg/l). However, some areas
      (1.0-9.2%) exhibited >10 MUg/l. Notably, urinary arsenic excretion of people
      around these regions was markedly higher compared with non-contaminated areas (<5
      MUg/l) (79.7+/-5.2 MUg/g (N=122) vs 68.4+/-5.4 MUg/g (N=65) creatinine, P=0.052).
      All stratified analysis also revealed higher urinary excretion, where a
      statistically significant difference was noted for non-smokers (85.9+/-12.7 vs
      54.0+/-6.3, P=0.030), suggesting that arsenic-contaminated groundwater may
      contribute to its systemic exposure.

PMID- 27049536
TI  - A principal factor analysis to characterize agricultural exposures among Nebraska
      veterans.
AB  - Agricultural workers are at an increased risk of developing chronic respiratory
      disorders. Accurate estimation of long-term agricultural exposures based on
      questionnaires has been used to improve the validity of epidemiologic
      investigations and subsequent evaluation of the association between agricultural
      exposures and chronic diseases. Our aim was to use principal factor analysis
      (PFA) to distill exposure data into essential variables characterizing long-term
      agricultural exposures. This is a cross-sectional study of veterans between the
      ages of 40 and 80 years and who worked on a farm for >=2 years. Participant
      characteristics were: 98.1% were white males with a mean age 65+/-8 (SD) years
      and 39.8% had chronic obstructive pulmonary disease. The final model included
      four factors and explained 16.6% of the variance in the exposure data. Factor 1
      was a heterogeneous factor; however, Factor 2 was exclusively composed of
      exposure to livestock such as hogs, dairy and poultry. Factor 3 included
      exposures from jobs on or off the farm such as wood dust, mineral dust, asbestos
      and spray paint. Crop exposure loaded exclusively in Factor 4 and included
      lifetime hours of exposure and maximum number of acres farmed in the
      participants' lifetime. The factors in the final model were interpretable and
      consistent with farming practices.

PMID- 27049537
TI  - Sound lateralization test in patients with unilateral microtia and atresia after
      reconstruction of the auricle and external canal and fitting of canal-type
      hearing aids.
AB  - CONCLUSION: In patients with unilateral microtia and atresia after reconstruction
      of the auricle and external canal and fitting of a canal-type hearing aid for the
      operated ear, the ability to discriminate the inter-aural intensity difference
      (IID) was acquired in all of the patients, whereas that to discriminate inter
      aural time difference (ITD) was acquired in one-half of the patients. OBJECTIVE:
      To study the post-operative sound lateralization ability in patients with
      unilateral microtia and atresia after reconstruction surgery of the auricle and
      external canal and fitting of a canal-type hearing aid of the operated ear.
      METHODS: Eighteen patients with unilateral microtia and atresia ranging from 13
      24 years of age were recruited in this study. All of them underwent
      reconstruction of the auricle and external canal and were fitted a canal-type
      hearing aid for the operated ear. The sound lateralization test was conducted to
      determine IID and ITD using a self-recording apparatus. The test stimulus was a
      continuous narrow-band noise at 500 Hz and 50 dBHL presented to the right and
      left ears through the air conduction receivers. RESULTS: IID could be measured in
      all of the patients, whereas ITD could be measured in only nine out of the 18
      patients. Post-operative binaural hearing could be acquired in all the patients.

PMID- 27049538
TI  - When Assessment Data Are Words: Validity Evidence for Qualitative Educational
      Assessments.
AB  - Quantitative scores fail to capture all important features of learner
      performance. This awareness has led to increased use of qualitative data when
      assessing health professionals. Yet the use of qualitative assessments is
      hampered by incomplete understanding of their role in forming judgments, and lack
      of consensus in how to appraise the rigor of judgments therein derived. The
      authors articulate the role of qualitative assessment as part of a comprehensive
      program of assessment, and translate the concept of validity to apply to
      judgments arising from qualitative assessments. They first identify standards for
      rigor in qualitative research, and then use two contemporary assessment validity
      frameworks to reorganize these standards for application to qualitative
      assessment.Standards for rigor in qualitative research include responsiveness,
      reflexivity, purposive sampling, thick description, triangulation, transparency,
      and transferability. These standards can be reframed using Messick's five sources
      of validity evidence (content, response process, internal structure,
      relationships with other variables, and consequences) and Kane's four inferences
      in validation (scoring, generalization, extrapolation, and implications).
      Evidence can be collected and evaluated for each evidence source or inference.
      The authors illustrate this approach using published research on learning
      portfolios.The authors advocate a "methods-neutral" approach to assessment, in
      which a clearly stated purpose determines the nature of and approach to data
      collection and analysis. Increased use of qualitative assessments will
      necessitate more rigorous judgments of the defensibility (validity) of inferences
      and decisions. Evidence should be strategically sought to inform a coherent
      validity argument.

PMID- 27049539
TI  - Increasing Scholarly Activity Productivity During Residency: A Systematic Review.
AB  - PURPOSE: Although resident participation in scholarly activity is mandated by the
      Accreditation Council for Graduate Medical Education, programmatic factors
      associated with success are not defined. This systematic review's objective was
      to determine which interventions are effective in increasing resident scholarly
      activity productivity (RSAP), as measured by participation in scholarly activity,
      presentations, or publications. METHOD: The PubMed, MEDLINE, Cochrane Library of
      Systematic Reviews, PsycINFO, CINAHL, and ERIC databases were searched through
      October 2013. English-language articles evaluating interventions to increase RSAP
      in U.S. or Canadian residency programs were included, without date limits. Two
      independent reviewers selected articles for inclusion and extracted data.
      Discrepancies were resolved by consensus. RESULTS: Of the 6,248 records screened,
      80 studies underwent data abstraction. Twenty-six described outcomes without a
      comparison group, leaving 54 studies representing 13 medical and surgical
      specialties. Interventions included required scholarly activity participation,
      protected research time, research curricula, research directors, dedicated
      research days, and research tracks. Focusing on the 35 studies reporting
      statistical analysis, RSAP was associated with all interventions. There were some
      differences in intervention effectiveness between medical and surgical
      specialties. CONCLUSIONS: Interventions, including protected time, research
      curricula, or specialized research tracks, generally result in increased
      participation in scholarly activity in residency programs, with mixed effects on
      resident presentations or publications. In many studies, interventions were
      bundled, suggesting that programs may need to provide increased structure and
      rigor through multiple pathways. The findings highlight the need for a clear
      definition of resident scholarly activity success aligned specifically to
      individual program and resident aims.

PMID- 27049540
TI  - How Prevalent Are Potentially Illegal Questions During Residency Interviews? A
      Follow-up Study of Applicants to All Specialties in the National Resident
      Matching Program.
AB  - PURPOSE: To describe the prevalence and effects on applicants of being asked
      potentially illegal questions during the residency interview process by surveying
      all residency applicants to all specialties. METHOD: The authors surveyed all
      applicants from U.S. medical schools to residency programs in all specialties in
      2012-2013. The survey included questions about the prevalence of potentially
      illegal questions, applicants' level of comfort with such questions, and whether
      such questions affected how applicants ranked programs. Descriptive statistics,
      tests of proportions, t tests, and logistic regression modeling were used to
      analyze the data. RESULTS: Of 21,457 eligible applicants, 10,976 (51.1%)
      responded to the survey. Overall, 65.9% (7,219/10,967) reported receiving at
      least one potentially illegal question. More female respondents reported being
      asked questions about gender (513/5,357 [9.6%] vs. 148/5,098 [2.9%]), marital
      status (2,895/5,283 [54.8%] vs. 2,592/4,990 [51.9%]), or plans for having
      children (889/5,241 [17.0%] vs. 521/4,931 [10.6%]) than male respondents (P <
      .001). Those in surgical specialties were more likely to have received a
      potentially illegal question than those in nonsurgical specialties (1,908/2,330
      [81.9%] vs. 5,311/8,281 [64.1%]). Questions regarding their commitment to the
      program were reported by 15.5% (1,608/10,378) of respondents. Such potentially
      illegal questions negatively affected how respondents ranked programs.
      CONCLUSIONS: Two-thirds of applicants reported being asked potentially illegal
      questions. More women than men reported receiving questions about marital status
      or family planning. Potentially illegal questions negatively influence how
      applicants perceive and rank programs. A formal interview code of conduct or
      interviewer training could help to address these issues.

PMID- 27049541
TI  - Health Systems Science Curricula in Undergraduate Medical Education: Identifying
      and Defining a Potential Curricular Framework.
AB  - PURPOSE: The authors performed a review of 30 Accelerating Change in Medical
      Education full grant submissions and an analysis of the health systems science
      (HSS)-related curricula at the 11 grant recipient schools to develop a potential
      comprehensive HSS curricular framework with domains and subcategories. METHOD: In
      phase 1, to identify domains, grant submissions were analyzed and coded using
      constant comparative analysis. In phase 2, a detailed review of all existing and
      planned syllabi and curriculum documents at the grantee schools was performed,
      and content in the core curricular domains was coded into subcategories. The lead
      investigators reviewed and discussed drafts of the categorization scheme,
      collapsed and combined domains and subcategories, and resolved disagreements via
      group discussion. RESULTS: Analysis yielded three types of domains: core, cross
      cutting, and linking. Core domains included health care structures and processes;
      health care policy, economics, and management; clinical informatics and health
      information technology; population and public health; value-based care; and
      health system improvement. Cross-cutting domains included leadership and change
      agency; teamwork and interprofessional education; evidence-based medicine and
      practice; professionalism and ethics; and scholarship. One linking domain was
      identified: systems thinking. CONCLUSIONS: This broad framework aims to build on
      the traditional definition of systems-based practice and highlight the need for
      medical and other health professions schools to better align education programs
      with the anticipated needs of the systems in which students will practice. HSS
      will require a critical investigation into existing curricula to determine the
      most efficient methods for integration with the basic and clinical sciences.

PMID- 27049542
TI  - Addressing the Irreducible Needs of Interprofessional Education: Creating and
      Sustaining an Institutional Commons for Health Professions Training.
AB  - Leaders in health professions education schools and programs are under pressure
      to respond to new accreditation requirements for interprofessional education
      (IPE). The work of creating and sustaining an IPE program at an academic health
      center is in many ways analogous to the challenge of creating and sustaining a
      "commons"-a set of resources shared by many, but owned by none. In this
      Commentary, the authors borrow from the work of Nobel Laureate Elinor Ostrum to
      describe the "design principles" necessary to build and maintain the set of
      common resources needed to successfully implement and sustain an IPE program.
      They interpret these principles in the context of their own experiences
      implementing IPE programs and recommend three institutional structural elements
      necessary to build and sustain an IPE program: (1) a representative governance
      body, (2) an accountable director or leader, and (3) a structure supporting
      vertical and horizontal communication and authority.

PMID- 27049543
TI  - Translating Research for Health Policy Decisions: Is It Time for Researchers to
      Join Social Media?
AB  - Identifying effective strategies to translate research evidence to policy is a
      national priority and a priority of the health policy research community.
      Multiple channels exist to disseminate, translate, and communicate research
      evidence. Some thought leaders have specifically advocated for researchers to
      play a direct role in research dissemination, particularly through social media.
      However, this view remains controversial. This Commentary explores the current
      state of and future opportunities and barriers for alternative avenues of policy
      relevant research dissemination. The authors identify four intersecting realities
      influencing the manner in which the health research community views and adopts
      various approaches to research translation: (1) persistent gaps in evidence
      translation and knowledge transfer, particularly in the realm of health policy;
      (2) public demand for scholars to embrace new modes of research dissemination;
      (3) the rapid growth and reach of social media to disseminate information; and
      (4) skepticism and confusion within the academic community about how best to use
      social media to disseminate policy-relevant research. They conclude that while
      scholars will need to be engaged in evidence translation to inform health policy,
      they may be best served by connecting with trusted intermediaries and knowledge
      brokers to promote efficient use of the best available evidence to answer the
      most timely policy questions. Journals and universities may be well positioned to
      invest in this capacity to curate research evidence and disseminate it using
      social media and other technologies.

PMID- 27049544
TI  - The Two-Stage Examination: A Method to Assess Individual Competence and
      Collaborative Problem Solving in Medical Students.
AB  - PROBLEM: Effectively solving problems as a team under stressful conditions is
      central to medical practice; however, because summative examinations in medical
      education must test individual competence, they are typically solitary
      assessments. APPROACH: Using two-stage examinations, in which students first
      answer questions individually (Stage 1) and then discuss them in teams prior to
      resubmitting their answers (Stage 2), is one method for rectifying this
      discordance. On the basis of principles of social constructivism, the authors
      hypothesized that two-stage examinations would lead to better retention of,
      specifically, items answered incorrectly at Stage 1.In fall 2014, they divided
      104 first-year medical students into two groups of 52 students. Groups alternated
      each week between taking one- and two-stage examinations such that each student
      completed 6 one-stage and 6 two-stage examinations. The authors reassessed 61
      concepts on a final examination and, using the Wilcoxon signed ranked tests,
      compared performance for all concepts and for just those students initially
      missed, between Stages 1 and 2. OUTCOMES: Final examination performance on all
      previously assessed concepts was not significantly different between the one-and
      two-stage conditions (P = .77); however, performance on only concepts that
      students initially answered incorrectly on a prior examination improved by 12%
      for the two-stage condition relative to the one-stage condition (P = .02, r =
      0.17). NEXT STEPS: Team assessment may be most useful for assessing concepts
      students find difficult, as opposed to all content. More research is needed to
      determine whether these results apply to all medical school topics and student
      cohorts.

PMID- 27049545
TI  - Scalable learning method for feedforward neural networks using minimal-enclosing
      ball approximation.
AB  - Training feedforward neural networks (FNNs) is one of the most critical issues in
      FNNs studies. However, most FNNs training methods cannot be directly applied for
      very large datasets because they have high computational and space complexity. In
      order to tackle this problem, the CCMEB (Center-Constrained Minimum Enclosing
      Ball) problem in hidden feature space of FNN is discussed and a novel learning
      algorithm called HFSR-GCVM (hidden-feature-space regression using generalized
      core vector machine) is developed accordingly. In HFSR-GCVM, a novel learning
      criterion using L2-norm penalty-based epsilon-insensitive function is formulated
      and the parameters in the hidden nodes are generated randomly independent of the
      training sets. Moreover, the learning of parameters in its output layer is proved
      equivalent to a special CCMEB problem in FNN hidden feature space. As most CCMEB
      approximation based machine learning algorithms, the proposed HFSR-GCVM training
      algorithm has the following merits: The maximal training time of the HFSR-GCVM
      training is linear with the size of training datasets and the maximal space
      consumption is independent of the size of training datasets. The experiments on
      regression tasks confirm the above conclusions. 

PMID- 27049546
TI  - Neurocognitive mechanisms of mathematical giftedness: A literature review.
AB  - Mathematically gifted children/adolescents have demonstrated exceptional
      abilities and traits in logical reasoning, mental imagery, and creative thinking.
      In the field of cognitive neuroscience, the past studies on mathematically gifted
      brains have concentrated on investigating event-related brain activation regions,
      cerebral laterality of cognitive functions, functional specialization that is
      uniquely dedicated for specific cognitive purposes, and functional interactions
      among discrete brain regions. From structural and functional perspectives, these
      studies have witnessed both "general" and "unique" neural characteristics of
      mathematically gifted brains. In this article, the theoretical background,
      empirical studies, and neurocognitive mechanisms of mathematically gifted
      children/adolescents are reviewed. Based on the integration of the findings, some
      potential directions for the future research are identified and discussed.

PMID- 27049547
TI  - Editorial.

PMID- 27049548
TI  - President's message. The perfect storm: Substance Abuse and Mental Health
      Services Administration (SAMHSA) Buprenorphine notice of proposed rule-making
      (NPRM).

PMID- 27049549
TI  - Centennial Celebration: Endocrine Reviews Past Highlights for March and April.

PMID- 27049550
TI  - Please Welcome the Latest Additions to Endocrine Reviews.

PMID- 27049553
TI  - Letter to the Editor: Response to "Second Scientific Statement on Endocrine
      Disrupting Chemicals" by Gore et al.

PMID- 27049554
TI  - Evidence of substance P autocrine circuitry that involves TNF-alpha, IL-6, and
      PGE2 in endogenous pyrogen-induced fever.
AB  - Substance P (SP) is involved in fever that is induced by lipopolysaccharide (LPS)
      but not by interleukin-1beta or macrophage inflammatory protein-1alpha.
      Intracerebroventricular (i.c.v.) administration of the neurokinin-1 (NK1)
      receptor antagonist SR140333B in rats reduced fever that was induced by an i.c.v.
      injection of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      prostaglandin E2 (PGE2), corticotropin-releasing factor (CRF), endothelin-1 (ET
      1), and morphine (MOR). Furthermore, an i.c.v. injection of SP induced a febrile
      response that was inhibited by indomethacin concomitant with an increase in PGE2
      levels in cerebrospinal fluid. Lipopolysaccharide and PGE2 caused higher
      expression and internalization of NK1 receptors in the hypothalamus which were
      prevented by SR140333B. These data suggest that SP is an important mediator of
      fever, in which it induces a prostaglandin-dependent response and is released
      after TNF-alpha, IL-6, PGE2, CRF, endogenous opioids, and ET-1. 

PMID- 27049555
TI  - PGE2 released by primary sensory neurons modulates Toll-like receptor 4
      activities through an EP4 receptor-dependent process.
AB  - Exogenous prostaglandin E2 (PGE2) displays mixed regulatory properties with
      regard to inflammatory gene expression in dorsal root ganglion (DRG) cells. We
      show here that endogenously-produced nanomolar concentrations of PGE2, such as
      that generated in response to Toll-like receptor 4 (TLR4) stimulation, inhibits
      both cyclooxygenase-2 (COX-2) and tumour necrosis factor alpha (TNFalpha) mRNA
      expression in DRG cells in an EP4 receptor-dependent manner. DRG neurons appear
      to be the major source of PGE2 in the DRG and likely serve as both an autocrine
      and paracrine system for limiting over-activation of both DRG neurons and glial
      cells in response to TLR4 stimulation. 

PMID- 27049556
TI  - A retrospective analysis of possible triggers of Guillain-Barre syndrome.
AB  - Antecedent infections have been found to be the most common trigger for Guillain
      Barre syndrome (GBS). In the present study, we retrospectively analyzed 36 adult
      patients with GBS and found that surgery, trauma and treatment with ganglioside
      were also common before the onset of GBS. The proportion of the axonal subtype of
      GBS in post-surgical/traumatic patients was higher than that in non
      surgical/traumatic patients (P=0.013) in the present study. In conclusion, this
      study has shown that prior infection, surgery, trauma and ganglioside may be
      clinical contributors to the onset of GBS and raised the possibility that they
      may act synergistically as triggers for the development of GBS. 

PMID- 27049557
TI  - Interleukin 6 promoter 174 G/C polymorphisms in acute ischemic stroke: G allele
      is protective but not associated with IL-6 levels or stroke outcome.
AB  - Our study investigated the frequency of interleukin-6 (IL-6) promoter
      polymorphism rs1800795 (-174 G>C), possible association of this polymorphism with
      IL-6 levels and the outcome after stroke in 95 patients with acute ischemic
      stroke and 268 healthy subjects. It shows a significant reduction in the
      frequency of G alleles in stroke patients compared to healthy controls. Carriage
      of G allele is not associated with stroke subtypes, the initial severity or the
      outcome after stroke. The -174 polymorphisms were not associated with variation
      in IL-6 levels post-stroke. Our results indicate that IL-6 promoter -174
      polymorphisms may play a role in susceptibility to stroke, but not stroke
      outcome. 

PMID- 27049558
TI  - Lesion length of optic neuritis impacts visual prognosis in neuromyelitis optica.
AB  - OBJECTIVES: The visual acuity prognoses of patients with neuromyelitis optica
      (NMO) are worse than those with optic neuritis (ON) caused by other diseases.
      Predicting the prognoses of ON at the time of onset is important for selecting
      treatments for NMO patients. METHODS: Twenty-three consecutive anti-aquaporin-4
      autoantibody-positive NMO patients who presented with ON and had contrast
      enhanced optic MRIs in the acute phase of their first ON episode were examined.
      Optical coherence tomographies (OCTs) were also examined for 22 of them. The
      visual acuity at the final follow-up, as assessed with the logMAR scale more than
      three years after ON onset, served as the outcome measure. These variables were
      also collected from 12 patients with serum anti-myelin oligodendrocyte
      glycoprotein antibody (anti-MOG-Ab). RESULTS: The strongest predictor of visual
      prognosis was the axial ON lesion length in the acute phase (R=0.747, p<0.0001),
      which was not observed in patients with anti-MOG-Ab. Specifically, the ON lesion
      length within the intra-orbit and canalicular segments exhibited the strongest
      correlation with visual prognosis (R=0.783, p<0.0001). The ON onset age was also
      correlated with visual prognosis (R=0.435, p=0.0338). OCT data in the chronic
      phase also showed a correlation with visual prognosis, but they were much weaker
      than the ON lesion length in the acute phase. CONCLUSIONS: The ON lesion length
      in the acute phase was an important predictor of the visual prognoses of NMO
      patients.

PMID- 27049559
TI  - Prevalence of antineuronal antibodies in patients with encephalopathy of unknown
      etiology: Data from a nationwide registry in Korea.
AB  - We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide
      cohort of patients with encephalopathy of unknown etiology. We screened 1699
      patients with idiopathic encephalopathy who were referred from 70 hospitals
      across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those
      with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic
      syndromes without encephalopathy were not included in this study. One-hundred and
      four patients (6.12%) had antibody-associated autoimmune encephalopathy.
      Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic
      paraneoplastic antibodies were identified in 16 patients (0.94%). The patients
      with antibody-associated autoimmune encephalopathy comprised a small but
      significant portion of the total number of patients with encephalopathy of
      unknown cause. 

PMID- 27049560
TI  - Cytokines in cerebrospinal fluid of neurosyphilis patients: Identification of
      Urokinase plasminogen activator using antibody microarrays.
AB  - Little is known regarding protein responses to syphilis infection in
      cerebrospinal fluid (CSF) of patients presenting with neurosyphilis. Protein and
      antibody arrays offer a new opportunity to gain insights into global protein
      expression profiles in these patients. Here we obtained CSF samples from 46
      syphilis patients, 25 of which diagnosed as having central nervous system
      involvement based on clinical and laboratory findings. The CSF samples were then
      analyzed using a RayBioH L-Series 507 Antibody Array system designed to
      simultaneously analyze 507 specific cytokines. The results indicated that 41
      molecules showed higher levels in patients with neurosyphilis in comparison with
      patients without neural involvement. For validation by single target ELISA, we
      selected five of them (MIP-1a, I-TAC/CXCL11, Urokinase plasminogen activator
      [uPA], and Oncostatin M) because they have previously been found to be involved
      in central nervous system (CNS) disorders. The ELISA tests confirmed that uPA
      levels were significantly higher in the CSF of neurosyphilis patients (109.1+/
      7.88pg/ml) versus patients without CNS involvement (63.86+/-4.53pg/ml, p<0.0001).
      There was also a clear correlation between CSF uPA levels and CSF protein levels
      (p=0.0128) as well as CSF-VDRL titers (p=0.0074) used to diagnose neurosyphilis.
      No significant difference between the two groups of patients, however, was found
      in uPA levels in the serum, suggesting specific activation of the inflammatory
      system in the CNS but not the periphery in neurosyphilis patients. We conclude
      that measurements of uPA levels in CSF may be an additional parameter for
      diagnosing neurosyphilis. 

PMID- 27049561
TI  - Estrogen induces multiple regulatory B cell subtypes and promotes M2 microglia
      and neuroprotection during experimental autoimmune encephalomyelitis.
AB  - Sex hormones promote immunoregulatory effects on multiple sclerosis. The current
      study evaluated estrogen effects on regulatory B cells and resident CNS microglia
      during experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an
      estrogen-dependent induction of multiple regulatory B cell markers indicative of
      IL-10 dependent as well as IFN-gamma dependent pathways. Moreover, although
      estrogen pretreatment of EAE mice inhibited the infiltration of pro-inflammatory
      cells into the CNS, it enhanced the frequency of regulatory B cells and M2
      microglia. Our study suggests that estrogen has a broad effect on the development
      of regulatory B cells during EAE, which in turn could promote neuroprotection. 

PMID- 27049562
TI  - Factors that impact health-related quality of life in neuromyelitis optica
      spectrum disorder: anxiety, disability, fatigue and depression.
AB  - AIMS: Neuromyelitis optica spectrum disorder (NMOSD) is associated with reduced
      health-related quality of life (HRQOL). This study aimed to investigate factors
      that impact HRQOL in NMOSD. METHODS: A series of questionnaires were completed by
      73 patients to assess the relationships between HRQOL and fatigue, depression,
      anxiety and sleep disorder. We also evaluated the contributions of clinical
      characteristics to HRQOL. Correlation and regression analysis were conducted to
      identify factors that negatively impact HRQOL in NMOSD. RESULTS: Pearson's
      correlation analysis showed that reduced HRQOL was strongly correlated with
      anxiety (r=-0.77, P=0.000), fatigue (r=-0.75, P=0.000) and depression (r=-0.73,
      P=0.000); and moderately correlated with disability (r=-0.53, P=0.000) and sleep
      disorder (r=-0.59, P=0.000). Stepwise regression analysis further revealed that
      anxiety was the best predictor of both the global and physical composite scores
      of HRQOL, followed by disability, fatigue and depression (global composite,
      r(2)=0.76, P=0.000; physical composite, r(2)=0.71, P=0.000). Depression, fatigue
      and anxiety were the main predictors of the mental health composite score of
      HRQOL (r(2)=0.69, P=0.000). Other factors did not have an effect on HRQOL.
      CONCLUSIONS: This study revealed factors that impact HRQOL in NMOSD and provided
      the first demonstration that anxiety, disability, fatigue and depression are
      independent predictors of poor HRQOL in NMOSD.

PMID- 27049563
TI  - Vitamin D receptor biochemical and genetic profiling and HLA-class II genotyping
      among Lebanese with multiple sclerosis - A pilot study.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease
      affecting mostly young adult females with multifactorial etiology. Recent studies
      suggested that adequate vitamin D levels may lower the risk of developing MS.
      OBJECTIVES: Our aim was to explore the relationship between vitamin D receptor
      (VDR) polymorphism, HLA-DR locus genotype, and serum vitamins D and A levels in
      the Lebanese population. METHODS: Fifty MS patients were recruited for this
      study. The control group consisted of 48 healthy and 51 patients with other
      neurological disorders (non-MS). Biochemical analysis included serum 25
      hydroxyvitamin D (25OHD) and vitamin A. Molecular analysis targeted VDR genotypes
      (ApaI, TaqI and BsmI) and low resolution HLA typing for DRB1 locus. RESULTS:
      Healthy and non-MS groups had comparable parameters and were combined into one
      control group. No significant differences were found between MS and control
      groups for VDR genotypes. The frequency of HLA-DRB1*15 was significantly higher
      in MS patients (22%) compared to controls (8%) (p=0.018). Odds ratio for MS in
      the presence of DRB1*15 allele was 3.21 (p=0.018). Cosegregation with A (ApaI)
      and b (BsmI) alleles did not influence the risk for MS. 25OHD levels were
      significantly higher in MS patients compared to controls (p=0.002), due to more
      frequent oral supplementation (p=0.005). Vitamin A levels were comparable between
      the two groups. When all parameters were included in a logistic regression model
      adjusted for supplementation, only HLA-DRB1*15 (OR=3.42; p=0.027) contributed
      significantly to MS risk. CONCLUSION: There was no association between serum
      vitamin D or A or VDR genotypes and MS. HLA-DRB1*15 was the major factor imposing
      more than 3 folds greater risk for developing MS among Lebanese.

PMID- 27049564
TI  - Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II
      associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel.
AB  - BACKGROUND: Previous studies have revealed different human leukocyte antigen
      (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO),
      further discriminating these two demyelinating pathological conditions. In
      worldwide analyses, NMO and opticospinal MS are represented at higher proportions
      among demyelinating conditions in African, East-Asian and Latin American
      populations. There are currently no data regarding the prevalence of NMO in
      Middle East Muslims. The population in Israel is diverse in many ways, and
      includes subpopulations, based on religion and ethnicity; some exhibit genetic
      homogeneity. In Israel, the incidence of MS is lower in the Muslim population
      than the Jewish population and Muslims carry different allele frequency
      distribution of HLA haplotypes. OBJECTIVE: To evaluate the occurrence of anti
      AQP4 seropositivity in the Israeli Muslim population among patients with central
      nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ
      profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD).
      METHODS: The prevalence of anti-AQP4 seropositivity was analyzed in 342 samples,
      obtained from patients with various CNS demyelinating conditions and in a
      validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were
      examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to
      available data from 74 Israeli Muslim controls. RESULTS: Our data reveal a
      significantly increased prevalence of anti-AQP4 seropositivity, indicative of
      NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS
      demyelinating syndrome. In this population, there was a positive association with
      the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative
      association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002).
      CONCLUSIONS: Our findings indicate a possibly increased prevalence of NMOSD in
      Muslim Arabs in Israel with distinct (positive and negative) HLA associations.
      Further studies in patients with similar genetic backgrounds worldwide could help
      to confirm our findings and identify more genetic susceptibility factors for NMO,
      contributing to our general understanding of the pathogenesis of NMOSD.

PMID- 27049565
TI  - Revelation of the IFNalpha, IL-10, IL-8 and IL-1beta as promising biomarkers
      reflecting immuno-pathological mechanisms in porcine Huntington's disease model.
AB  - Studies on Huntington's disease (HD) demonstrated altered immune response in HD
      gene carriers. Using multiplexing immunoassay, we simultaneously investigated
      seven cytokines in secretomes of microglia and blood monocytes, cerebrospinal
      fluid (CSF) and serum collected from transgenic HD minipigs at pre-symptomatic
      disease stage. Decline in IFNalpha and IL-10 was observed in CSF and secretome of
      microglia whilst elevated IL-8 and IL-1beta levels were secreted by microglia.
      Additionally, IL-8 was increased in serum. The proportion of mutant huntingtin in
      microglia may have causative impact on cytokine production. IFNalpha, IL-10, IL-8
      and IL-1beta represent promising biomarkers reflecting immuno-pathological
      mechanisms in porcine HD model. 

PMID- 27049566
TI  - A study of the utility of azathioprine metabolite testing in myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterised by
      fatigable voluntary skeletal muscle weakness. The underlying pathogenesis is
      complex involving adaptive autoimmune responses. Azathioprine remains a first
      line broad acting immunosuppressant for MG. Due to varied clinical responses to
      azathioprine we aimed to investigate the relationship between azathioprine
      metabolites and symptom control. Mild correlations between Quantitative
      Myasthenia Gravis Score (QMG) vs. 6-thioguanine nucleotides (R=-0.317 p=0.186)
      and QMG vs. lymphocyte count (R=0.402 p=0.08) were found. Azathioprine metabolite
      measurement should be considered in MG patients with; pancytopenia, deranged
      liver function or recurrent infections. 

PMID- 27049567
TI  - Is there a role for Mycobacterium avium subspecies paratuberculosis in
      Parkinson's disease?
AB  - In Parkinson's disease (PD) ZnT proteins play an important role. Zinc is a co
      factor of numerous enzymes and stabilizes the tertiary structure of several
      proteins. Nothing is known about previous infections mediated by Mycobacterium
      avium subsp. paratuberculosis (MAP). We evaluated if a previous infection with
      MAP could induce the production of antibodies that cross-reacted with the Znt
      homologous antigenic peptides associated to Parkinson. The humoral response
      toward MAP3865c peptides, ZnT3 and ZnT10 was evaluated. The hypothesis of cross
      reactivity needs to be confirmed; we have observed the presence of MAP in PD
      patients by PCR, positivity to MAP3865c peptides, therefore MAP infection but not
      cross-reaction with human homologous Znt proteins. 

PMID- 27049568
TI  - Combined exercise training reduces fatigue and modulates the cytokine profile of
      T-cells from multiple sclerosis patients in response to neuromediators.
AB  - Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical
      Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological
      treatment for fatigue, but some reports point towards beneficial effects of
      physical activity on management of the fatigue in MS patients. As both MS and
      fatigue have been associated with dysregulated cytokine network production, the
      objective of the present study was to evaluate the impact of a physical activity
      program consisting of a 12-week series of combining Pilates and aerobic exercises
      on fatigue severity, determined by FSS, and cytokine production, quantified by
      ELISA, by T cells from MS patients (n=08) with low disability (EDSS<=2). The
      results showed decrease in FSSs in all patients at the end of physical activity
      intervention. Regarding the cytokines, a significant reduction of IL-22 release
      was observed in polyclonally-activated T cells form MS patients post-training
      follow-up. Interestingly, while the physical activity attenuated the ability of
      dopamine in up-regulating Th17-related cytokines, it enhanced the anti
      inflammatory effects of serotonin, evidenced by high IL-10 production. In
      summary, all results suggest that programmed physical activity has beneficial
      effects on management of fatigue in MS patients, and it could be related, at
      least in part, to its ability in regulating neuroimmune parameters into T cell
      compartment. 

PMID- 27049569
TI  - Decreased serum IL-27 and IL-35 levels are associated with disease severity in
      neuromyelitis optica spectrum disorders.
AB  - The interleukin 12 (IL-12) family plays important roles in autoimmune diseases.
      To explore the roles of the IL-12 family members IL-27 and IL-35 in the
      pathogenesis of neuromyelitis optica spectrum disorders (NMOSD), we determined
      their serum and cerebral spinal fluid levels and assessed potential correlations
      with clinical characteristics. Serum IL-27 levels were negatively correlated with
      disease severity and spinal cord lesion length, while serum IL-35 levels were
      negatively correlated with disease severity and annual relapse rate. Thus, IL-27
      and IL-35 may be important biomarkers of NMOSD severity and these molecules might
      represent potential therapeutic cytokines for treating NMOSD. 

PMID- 27049570
TI  - Splenectomy following MCAO inhibits the TLR4-NF-kappaB signaling pathway and
      protects the brain from neurodegeneration in rats.
AB  - BACKGROUND AND PURPOSE: The Toll-like receptor 4(TLR4)/nuclear factor kappa B NF
      kappaB inflammatory pathway contributes to secondary inflammation in many
      diseases including stroke. Moreover, the neuroprotective effect of splenectomy in
      stroke is supported by a vast body of experimental evidence. Nevertheless, the
      underlying mechanism(s) by which splenectomy enhance neuroprotection in stroke is
      still poorly understood. Our study aimed to investigate whether post-ischemic
      splenectomy modulate the TLR4/NF-kappaB inflammatory pathway in stroke. METHODS:
      Immunohistochemistry was used to evaluate the levels of TLR4 and NF-kappaB
      expression in brain areas (parietal lobe, hippocampus and striatum) of rats that
      underwent: MCAO-splenectomy surgery (MS ); MCAO surgery without splenectomy (MCAO
      control or MC); Sham MCAO and splenectomy surgery (sham control group or SC group
      respectively. Apoptosis in these areas was assessed by TUNEL detection technique.
      RESULTS: The levels of TLR4 and NF-kappaB expression were significantly reduced
      in splenectomized rats relative to the MS group (P<0.01). Additionally, the
      number of apoptotic cells in the ischemic hemisphere were significantly higher in
      both MCAO groups compared to the Sham group (P<0.05), between day 1 and day 7. An
      exception was observed in the striatum where the difference in apoptotic rate
      between the MS and sham group was not statistically significant at the same time
      points. Moreover, the variation apoptotic rate in different cerebral zone
      correlated to variation in TLR4 and NF-kappaB expression. CONCLUSION: In summary,
      our study provides further evidence of neuroprotective effect of splenectomy in
      ischemic stroke. Our results suggest that such an effect might be due to the
      inhibition of theTLR4/NF-kappaB inflammatory pathway.

PMID- 27049571
TI  - Systemic ocular antigen immunization leads only to a minor secondary immune
      response.
AB  - The immunization with optic nerve homogenate antigen (ONA) or S100 induced
      retinal degeneration. Since many neurological diseases are reinforced or
      initiated by immune cells, leucocytes were analyzed. CD3(+) T-cells in the retina
      increased slightly in ONA rats, but not in S100 treated retinas. No CD45R(+) B
      cells and granulocytes could be detected in the retinas. At early stages, CD3(+)
      cells, Iba1(+) macrophages and granulocytes of the secondary lymphoid organs were
      not affected. Yet, the sole injection of pertussis toxin led to a shift to fewer
      CD45R(+) cells and more granulocytes in spleens. Later, splenic Iba1(+)
      macrophages were increased in both groups. We conclude that the retinal
      infiltration of lymphocytes is not crucial for the degeneration process and
      rather an epiphenomenon. 

PMID- 27049572
TI  - A study of TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma gene polymorphisms in
      patients with depression.
AB  - In the last decade it was found that functional polymorphisms in the promoter
      and/or coding regions of regulatory genes are likely to pre-determine the
      phenotype manifestation of a certain cytokine profile, and thus could be used as
      disease-associated markers. Having in mind the hypothesis of impaired cytokine
      regulation in depressive disorder, as well as the diverse population-dependent
      results for cytokine polymorphisms, we investigated the relation between the
      cytokine gene polymorphisms of key pro- and anti-inflammatory cytokines (TNF
      alpha, TGF-beta, IL-10, IL-6, IFN-gamma) and susceptibility as well as clinical
      course of depression in Bulgarians. The study included 80 patients with
      depression (50 women and 30 men) and 50 healthy controls. Simultaneous analysis
      of eight polymorphic positions in the cytokine genes listed was performed by PCR
      SSP method. The results revealed significant predominance of TGF-beta TT (+869)
      genotype (previously described as predicting low expression activity of TGF-beta)
      in patients (41.3%) compared to healthy subjects (21.2%) (p=0.05, OR=2.62).
      Furthermore T/T G/C combined genotype (+869, +915) in the same gene was
      negatively associated with disease recurrence. Additionally we found that certain
      IL-10 genotypes associated with low gene expression seemed to shape moderate
      disease manifestation. In conclusion our results mainly demonstrated prevalence
      of a low-expression TGF-beta1 profile in the patients. Thus, although in an
      indirect way, we supported the hypothesis of impaired immunosuppression by means
      of Th3 regulation in major depressive disorders. 

PMID- 27049573
TI  - Activation of the adenosine A2A receptor exacerbates experimental autoimmune
      neuritis in Lewis rats in association with enhanced humoral immunity.
AB  - Accumulated evidence demonstrated that Adenosine A2A receptor (A2AR) is involved
      in the inflammatory diseases. In the present study, we showed that a selective
      A2AR agonist, CGS21680, exacerbated experimental autoimmune neuritis in Lewis
      rats induced with bovine peripheral myelin. The exacerbation was accompanied with
      reduced CD4(+)Foxp3(+) T cells, increased CD4(+)CXCR5(+) T cells, B cells,
      dendritic cells and antigen-specific autoantibodies, which is possibly due to the
      inhibition of IL-2 induced by CGS21680. Combined with previous studies, our data
      indicate that the effects of A2AR stimulation in vivo are variable in different
      diseases. Caution should be taken in the use of A2AR agonists. 

PMID- 27049574
TI  - HIV-exposed, uninfected infants: new global challenges in the era of paediatric
      HIV elimination.
AB  - The number of infants infected with HIV is declining with the rise in
      interventions for the elimination of paediatric HIV infection, but the number of
      uninfected infants exposed to HIV through their HIV-infected mothers is
      increasing. Interest in the health outcomes of HIV-exposed, uninfected infants
      has grown in the past decade, with several studies suggesting that these infants
      have increased mortality rates, increased infectious morbidity, and impaired
      growth compared with HIV-unexposed infants. However, heterogeneous results might
      reflect the inherent challenges in studies of HIV-exposed, uninfected infants,
      which need large populations with appropriate, contemporaneous comparison groups
      and repeated HIV testing throughout the period of breastfeeding. We review the
      effects of HIV exposure on mortality, morbidity, and growth, discuss the
      immunological abnormalities identified so far, and provide an overview of
      interventions that could be effective in this susceptible population. As the
      number of infants infected with HIV declines, the health needs of HIV-exposed,
      uninfected infants should be prioritised further, to ensure that post-2015
      Sustainable Development Goals are achieved.

PMID- 27049575
TI  - In search of the HPA axis activity in unipolar depression patients with childhood
      trauma: Combined cortisol awakening response and dexamethasone suppression test.
AB  - The aim of the present study was to examine the impact of childhood trauma on HPA
      axis activity both in depression patients and healthy controls in order to
      determine the role of HPA axis abnormalities in depression and to find the
      differences in HPA axis functioning that may lead certain individuals more
      susceptible to the depressogenic effects of childhood trauma. Eighty subjects
      aged 18-45 years were recruited into four study groups (n = 18, depression
      patients with childhood trauma exposures, CTE/MDD; n = 17, depression patients
      without childhood adversity, non-CTE/MDD; n = 23, healthy persons with childhood
      trauma, CTE/non-MDD; and n = 22, healthy persons without childhood adversity, non
      CTE/non-MDD). Each participant collected salivary samples in the morning at four
      time points: immediately upon awakening, 30, 45, and 60 min after awakening for
      the assessment of CAR and underwent a 1 mg-dexamethasone suppression test (DST).
      Regardless of depression, subjects with CTE exhibited an enhanced CAR and the CAR
      areas under the curve to ground (AUCg) were associated with their childhood
      trauma questionnaire (CTQ) physical neglect scores and CTQ total scores. In
      addition, the CTE/MDD group also showed a highest post-DST cortisol concentration
      and a decreased glucocorticoid feedback inhibition among four groups of subjects.
      The present findings suggested that childhood trauma was associated with
      hyperactivity of HPA axis as measured with CAR, potentially reflecting the
      vulnerability for developing depression after early life stress exposures.
      Moreover, dysfunction of the GR-mediated negative feedback control might
      contribute to the development of depression after CTE.

PMID- 27049576
TI  - Hybrid SPECT/CT using 3D reconstruction with 99mTc-HMPAO-labeled leukocytes in
      the diagnosis of an infectious process of unknown origin in foot.

PMID- 27049577
TI  - Tandem virtual screening targeting the SRA domain of UHRF1 identifies a novel
      chemical tool modulating DNA methylation.
AB  - Ubiquitin-like protein UHRF1 that contains PHD and RING finger domain 1 is a key
      epigenetic protein enabling maintenance of the DNA methylation status through
      replication. A tandem virtual screening approach was implemented for identifying
      small molecules able to bind the 5-methylcytosine pocket of UHRF1 and inhibit its
      functionality. The NCI/DTP small molecules Repository was screened in silico by a
      combined protocol implementing structure-based and ligand-based methodologies.
      Consensus ranking was utilized to select a set of 27 top-ranked compounds that
      were subsequently evaluated experimentally in a stepwise manner for their ability
      to demethylate DNA in cellulo using PCR-MS and HPLC-MS/MS. The most active
      molecules were further assessed in a cell-based setting by the Proximity Ligation
      In Situ Assay and the ApoTome technology. Both evaluations confirmed that the
      DNMT1/UHRF1 interactions were significantly reduced after 4 h of incubation of
      U251 glioma cells with the most potent compound NSC232003, showing a 50%
      interaction inhibition at 15 MUM as well as induction of global DNA cytosine
      demethylation as measured by ELISA. This is the first report of a chemical tool
      that targets UHRF1 and modulates DNA methylation in a cell context by potentially
      disrupting DNMT1/UHRF1 interactions. Compound NSC232003, a uracil derivative
      freely available by the NCI/DTP Repository, provides a versatile lead for
      developing highly potent and cell-permeable UHRF1 inhibitors that will enable
      dissection of DNA methylation inheritance. 

PMID- 27049578
TI  - Exposure of methyl mercury in utero and the risk of neural tube defects in a
      Chinese population.
AB  - To determine if exposure to methyl mercury (MeHg) in utero is associated with an
      elevated risk of neural tube defects (NTDs), we measured its concentration in the
      placentas of 36 anencephalic and 44 spina bifida cases, as well as in 50 healthy
      controls. The median MeHg concentration in NTD cases (0.49ng/g) was higher than
      that in controls (0.33ng/g). The crude and adjusted odds ratios (ORs) for a MeHg
      concentration above the median were 3.54 (95% confidence interval (CI), 1.68
      7.49) and 3.64 (95% CI, 1.66-7.99), respectively. Both anencephaly and spina
      bifida subtypes had higher levels of MeHg than the controls. NTD risk increased
      for subjects in the second and third highest tertile of MeHg concentrations, with
      an OR of 2.24 (95% CI, 0.93-5.40) and 2.85 (95% CI, 1.17-6.94), respectively. In
      summary, higher placental levels of MeHg are associated with an elevated risk of
      NTDs.

PMID- 27049579
TI  - Environmental cadmium and lead exposure and anti-Mullerian hormone in pregnant
      women.
AB  - BACKGROUND: Anti-Mullerian Hormone (AMH) has been suggested as a marker for
      ovarian function. Cadmium and lead have been suggested to reduce female
      fecundity. In this study we aimed to investigate whether environmental exposure
      to cadmium and lead was associated with alterations in serum-AMH. MATERIALS AND
      METHOD: The associations between serum-AMH and whole blood cadmium or lead were
      investigated by general linear models in a population-based sample of 117
      pregnant women. RESULTS: The mean concentrations of blood cadmium and lead were
      0.71MUg/L and 17.4MUg/L, respectively. The mean serum-AMH was 17.3pmol/L. No
      association between lead and AMH was detected. In the cadmium analysis the
      adjusted mean AMH level (95% CI) in the highest exposure tertile was 12.4
      (6.4;23.8) compared to 5.6 (2.7;11.4) in the lowest exposure tertile (p=0.06).
      CONCLUSION: The study provides suggestive evidence that environmental exposure to
      cadmium, but not lead, may alter the level of AMH.

PMID- 27049580
TI  - Perinatal exposure to mixtures of endocrine disrupting chemicals reduces female
      rat follicle reserves and accelerates reproductive aging.
AB  - Exposure to endocrine disrupting chemicals (EDCs) during development can have
      negative consequences later in life. In this study we investigated the effect of
      perinatal exposure to mixtures of human relevant EDCs on the female reproductive
      system. Rat dams were exposed to a mixture of phthalates, pesticides, UV-filters,
      bisphenol A, butylparaben, as well as paracetamol. The compounds were tested
      together (Totalmix) or in subgroups with anti-androgenic (AAmix) or estrogenic
      (Emix) potentials. Paracetamol was tested separately. In pre-pubertal rats, a
      significant reduction in primordial follicle numbers was seen in AAmix and PM
      groups, and reduced plasma levels of prolactin was seen in AAmix. In one-year-old
      animals, the incidence of irregular estrous cycles was higher after Totalmix
      exposure and reduced ovary weights were seen in Totalmix, AAmix, and PM groups.
      These findings resemble premature ovarian insufficiency in humans, and raises
      concern regarding potential effects of mixtures of EDCs on female reproductive
      function.

PMID- 27049581
TI  - Non-cigarette tobacco and poly-tobacco use among persons living with HIV drawn
      from a nationally representative sample.
AB  - INTRODUCTION: Smoking is more prevalent among persons living with HIV (PLWH) than
      the general population. Little is known about the prevalence of non-cigarette
      tobacco and poly-tobacco use (PTU; using multiple tobacco products) among this
      population, which, in the general population is associated with poor health and
      cessation outcomes. We aimed to characterize the prevalence of cigarette and non
      cigarette tobacco use, PTU, and correlates of tobacco use status among a
      nationally-representative sample of PLWH. METHODS: Data came from 472 HIV
      positive adults from the 2005-2013 National Survey on Drug Use and Health
      (NSDUH). RESULTS: The prevalence of PTU overall was 8.7% (95% CI=5.6-13.2), and
      16.6% (95% CI=10.2-25.7) among past-year tobacco users. In multinomial logistic
      regression analyses, participants with a high school education or greater
      (aRRR=2.03, 95% CI=1.03-4.00) were more likely to be non-tobacco users than
      single product users. Past year drug users (aRRR=0.35, 95% CI=0.19-0.66) and past
      month binge drinkers (aRRR=0.24, 95% CI=0.12-0.50) were less likely to be non
      tobacco users than single product users. Compared to 18-25 year olds, individuals
      age 26-34 (aRRR=0.13, 95% CI=0.03-0.65) and 35+ (aRRR=0.24, 95% CI=0.09-0.63),
      and with lifetime anxiety disorder(s) (aRRR=0.18, 95% CI=0.06-0.57) were less
      likely to be PTUs as compared to single product users. Individuals who reported
      liking to test themselves by doing risky things were more likely to be PTUs than
      single product users (aRRR=2.95, 95% CI=1.27-6.84). CONCLUSIONS: PTU was slightly
      higher than in the general population, and should be taken into account when
      developing cessation interventions tailored to tobacco users living with HIV.

PMID- 27049582
TI  - Pain, alcohol use disorders and risky patterns of drinking among people with
      chronic non-cancer pain receiving long-term opioid therapy.
AB  - BACKGROUND: The utilisation of pharmaceutical opioids has increased
      internationally, and there is evidence of increasing risky alcohol consumption
      with ageing. This study examines the patterns and correlates of risky drinking
      among people with chronic non-cancer pain (CNCP) prescribed opioids, and the
      associations between alcohol consumption and pain. METHODS: The Pain and Opioids
      IN Treatment cohort comprises 1514 people in Australia prescribed pharmaceutical
      opioids for CNCP. Participants reported lifetime, past year and past month
      alcohol use, as well as mental and physical health, other substance use, pain
      characteristics, and current opioid dose. RESULTS: Less than one-tenth of the
      sample were 'lifetime abstainers' (7%); 34% were 'former drinkers'; 34% were 'non
      risky drinkers' (i.e., past 12 month use <=4 standard drinks); 16% were
      'occasional risky drinkers'; and 8% were 'regular risky drinkers' (i.e., >=weekly
      use of >4 standard drinks). Males reported greater levels of alcohol use, and a
      third (33%) of the total sample reported a lifetime alcohol use disorder.
      Controlling for demographics, mental health, physical health and substance use
      disorder history, 'former drinkers' (cf. 'non-risky drinkers') reported higher
      pain severity and interference ratings, and lower pain coping. 'Occasional risky
      drinkers' and 'regular risky drinkers' (cf. 'non-risky drinkers') reported higher
      levels of pain interference. CONCLUSIONS: Among people with CNCP, those who
      abstained from alcohol or drank at risky levels reported poorer pain outcomes
      compared with moderate drinkers. Early identification and intervention for risky
      drinking among people is critical, particularly given the risks associated with
      co-administration of alcohol and opioids.

PMID- 27049583
TI  - Intrinsic Defense Mechanisms of the Intestinal Epithelium.
AB  - The intestinal epithelium is a single cell layer that facilitates the absorption
      of nutrients but also provides a tight barrier to prevent pathogen invasion and
      dissemination of commensal microbes. Specialized epithelial cells of the
      gastrointestinal tract achieve this frontline defense by working in concert with
      lymphoid, myeloid, and stromal cells to secrete an array of factors that limit
      direct contact between the epithelium and infectious agents. The importance of
      these mechanisms is underscored by the ability of enteric pathogens to target
      these mechanisms to achieve invasion and dissemination. This review highlights
      recent advances in our understanding of these intricate molecular and cellular
      mechanisms adopted by these cells to promote spatial segregation and barrier
      maintenance.

PMID- 27049584
TI  - Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to
      Decreased Relative Fitness during Host Switching.
AB  - The emergence of mosquito-borne RNA viruses, such as West Nile virus (WNV), is
      facilitated by genetically complex virus populations within hosts. Here, we
      determine whether WNV enzootic (Culex tarsalis, Cx. quinquefasciatus, and Cx.
      pipiens) and bridge vectors (Aedes aegypti) have differential impacts on viral
      mutational diversity and fitness. During systemic mosquito infection, WNV faced
      stochastic reductions in genetic diversity that rapidly was recovered during
      intra-tissue population expansions. Interestingly, this intrahost selection and
      diversification was mosquito species dependent with Cx. tarsalis and Cx.
      quinquefasciatus exhibiting greater WNV divergence. However, recovered viral
      populations contained a preponderance of potentially deleterious mutations (i.e.,
      high mutational load) and had lower relative fitness in avian cells compared to
      input virus. These findings demonstrate that the adaptive potential associated
      with mosquito transmission varies depending on the mosquito species and carries a
      significant fitness cost in vertebrates.

PMID- 27049585
TI  - Long non-coding RNA Databases in Cardiovascular Research.
AB  - With the rising interest in the regulatory functions of long non-coding RNAs
      (lncRNAs) in complex human diseases such as cardiovascular diseases, there is an
      increasing need in public databases offering comprehensive and integrative data
      for all aspects of these versatile molecules. Recently, a variety of public data
      repositories that specialized in lncRNAs have been developed, which make use of
      huge high-throughput data particularly from next-generation sequencing (NGS)
      approaches. Here, we provide an overview of current lncRNA databases covering
      basic and functional annotation, lncRNA expression and regulation, interactions
      with other biomolecules, and genomic variants influencing the structure and
      function of lncRNAs. The prominent lncRNA antisense noncoding RNA in the INK4
      locus (ANRIL), which has been unequivocally associated with coronary artery
      disease through genome-wide association studies (GWAS), serves as an example to
      demonstrate the features of each individual database.

PMID- 27049586
TI  - Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or
      siltuximab following CAR T cell therapy.
AB  - T cells expressing a CD19-specific chimeric antigen receptor (CAR19) are
      demonstrating remarkable efficacy in hematologic malignancies. Treatment is often
      associated with life-threatening cytokine release syndrome (CRS) which can be
      effectively treated with cytokine blockade using the antibodies, Siltuximab or
      Tocilizumab respectively targeting IL-6 or the IL-6 receptor. As IL-6 blockade is
      moving into the clinic for the treatment of CRS as well as IL-6-driven
      rheumatologic and malignant diseases, clinicians are utilizing serum cytokine
      panels more frequently to assess the effects of IL-6 inhibitors. It is paramount
      to ascertain whether levels obtained are accurate, especially as certain drugs
      may, in theory, affect quantification. We report the comparative quantification
      of IL-6 and sIL-6R using Luminex-based immunoassay kits from two vendors. Our
      results indicate good agreement of the commercial immunoassays in measurement of
      IL-6 but disagreement in quantitation of sIL-6R. We found that both Siltuximab
      and Tocilizumab can interfere with the measurement of their respective ligands
      using reagents from one vendor but not the second. This has significant
      implications for the analysis of IL-6 and sIL-6R pharmacokinetics analysis in
      Siltuximab or Tocilizumab-treated patients. We found that high levels of IL-6 can
      falsely reduce the measured levels of sIL-6R and high levels of sIL-6R can reduce
      levels of IL-6 when measured with some commercial assays. These data demonstrate
      the importance of assessing the impact of cytokine-blocking agents on accuracy of
      clinical biomarker assays in other diseases, as drugs targeting TNF-alpha, IL1B,
      and IL5 are being used more frequently in a large number of diseases.

PMID- 27049587
TI  - The first report of NDM-5-producing uropathogenic Escherichia coli isolates in
      South Korea.

PMID- 27049588
TI  - College Students' Sense of Coherence and Connectedness as Predictors of Suicidal
      Thoughts and Behaviors.
AB  - This study aimed to explore the relationship between college students' sense of
      coherence and connectedness and their development of suicidal thoughts and
      behaviors. Using archival data from a larger survey with responses from 26,742
      undergraduate and graduate students at 74 colleges and universities, we applied
      Exploratory Factor Analysis to derive these protective factors (coherence and
      connectedness) as well as hypothesized distal and proximal risk factors (pre
      existing vulnerabilities and distress). Structural Equation Modeling was used to
      explore latent variable interactions among these factors with regards to outcomes
      on a continuum of suicidal thinking and behavior. Sense of coherence mitigated
      the impact of pre-existing vulnerabilities on movement along the continuum, while
      connectedness mitigated the impact of distress. Findings suggest that including
      both connectedness and coherence in suicide prevention frameworks will increase
      the impact of suicide prevention programming.

PMID- 27049589
TI  - What do I do? Developing a competency inventory for postgraduate (residency)
      program directors.
AB  - BACKGROUND: Few new Residency Program Directors (PD) are formally trained for the
      demands and responsibilities of the leadership aspect of their role. Currently,
      there are no comprehensive frameworks that describe specific leadership
      competencies that can inform PD self-reflection or faculty development. METHODS:
      The authors developed a Postgraduate Program Director Competency Inventory
      (PPDCI) in order to frame the performance of PDs for a multisource feedback (MSF)
      program. The development of the PPDCI occurred in five phases which involved:
      development of an initial inventory, implementation of a key informant survey of
      national opinion leaders, execution of a validity survey with postgraduate
      education leaders and committee members and implementation of a further refined
      inventory with 17 PD and 147 raters as part of a pilot MSF program. OUTCOMES:
      Five distinct domains of leadership competence were identified which included:
      Communication and relationship management, leadership, professionalism and self
      management, environmental engagement, and management skills and knowledge. The
      content validity of the PPDCI was endorsed by 85% of the key informants. The
      validity survey indicated strong endorsement of the PPDCI domains and recognition
      of its utility for both orientation of new PD as well as a frame for self
      assessment. The pilot MSF program yielded a further refined and reduced inventory
      of 26 items of competence as well as recommendations for its utility.
      CONCLUSIONS: Use of this leadership inventory has the potential to ensure
      effective leadership of postgraduate programs.

PMID- 27049592
TI  - Heteromerization of G2A and OGR1 enhances proton sensitivity and proton-induced
      calcium signals.
AB  - Proton-sensing G-protein-coupled receptors (GPCRs; OGR1, GPR4, G2A, TDAG8), with
      full activation at pH 6.4 ~ 6.8, are important to pH homeostasis, immune
      responses and acid-induced pain. Although G2A mediates the G13-Rho pathway in
      response to acid, whether G2A activates Gs, Gi or Gq proteins remains debated. In
      this study, we examined the response of this fluorescence protein-tagged OGR1
      family to acid stimulation in HEK293T cells. G2A did not generate detectable
      intracellular calcium or cAMP signals or show apparent receptor redistribution
      with moderate acid (pH >= 6.0) stimulation but reduced cAMP accumulation under
      strong acid stimulation (pH <= 5.5). Surprisingly, coexpression of OGR1- and G2A
      enhanced proton sensitivity and proton-induced calcium signals. This alteration
      is attributed to oligomerization of OGR1 and G2A. The oligomeric potential
      locates receptors at a specific site, which leads to enhanced proton-induced
      calcium signals through channels.

PMID- 27049593
TI  - Necessity of enzymatic hydrolysis for production and functionalization of
      nanocelluloses.
AB  - Nanocellulose (NC) from cellulosic biomass has recently gained attention owing to
      their biodegradable nature, low density, high mechanical properties, economic
      value and renewability. They still suffer, however, some drawbacks. The
      challenges are the exploration of raw materials, scaling, recovery of chemicals
      utilized for the production or functionalization and most important is toxic
      behavior that hinders them from implementing in medical/pharmaceutical field.
      This review emphasizes the structural behavior of cellulosic biomass and
      biological barriers for enzyme interactions, which are pertinent to understand
      the enzymatic hydrolysis of cellulose for the production of NCs. Additionally,
      the enzymatic catalysis for the modification of solid and NC is discussed. The
      utility of various classes of enzymes for introducing desired functional groups
      on the surface of NC has been further examined. Thereafter, a green mechanistic
      approach is applied for understanding at molecular level.

PMID- 27049594
TI  - Clozapine treatment and discontinuation in Iceland: A national longitudinal study
      using electronic patient records.
AB  - BACKGROUND: Clozapine is the only drug approved for treatment-resistant
      schizophrenia. There is evidence that clozapine is underutilized. AIMS: To
      evaluate the initiation and discontinuation of clozapine at Landspitali
      University Hospital in Iceland and the prevalence of antipsychotic polypharmacy
      in clozapine-treated patients. METHODS: The study is a part of an ongoing
      longitudinal study of schizophrenia in Iceland. We identified 201 patients on
      clozapine or who have been on clozapine by using a keyword search in the
      electronic health records and by reviewing their medical records. RESULTS: Mean
      age at first treatment with clozapine was 37.8 years. Mean follow-up period on
      clozapine was 11 years. After 20 years of treatment 71.2% of patients were still
      on clozapine. After one year of treatment 84.4% of patients were still receiving
      clozapine treatment. We estimate that 11.4% of patients with schizophrenia in
      Iceland are taking clozapine and that 16% have been treated with clozapine at
      some point. Polypharmacy is common, since nearly 2/3, 65.6%, of patients taking
      clozapine use at least one other antipsychotic and 16.9% are also receiving depot
      injections. CONCLUSIONS: We need to increase the awareness of psychiatrists in
      Iceland with regard to treatment with clozapine, since only about half of the
      estimated population of patients with treatment-resistant schizophrenia in
      Iceland have ever been treated with clozapine. Nearly two thirds of patients who
      are prescribed clozapine in Iceland remain on it long-term.

PMID- 27049595
TI  - Unpacking the "Pleasures" and "Pains" of Heterosexual Casual Sex: Beyond Singular
      Understandings.
AB  - Discussions of heterosexual casual sex are often imbued with (gendered)
      assumptions regarding the motives for, and drawbacks of, such a practice. The
      pulls of casual sex are often depicted as sexual gratification and the drawbacks
      relayed in terms of physical risk, for example, sexually transmitted infections
      (STIs)/human immunodeficiency virus (HIV) transmission. Most of the research in
      this area has largely focused on undergraduate university students or "emerging
      adults" in North America, using primarily quantitative methodologies. We build on
      this work and a small but growing amount of qualitative research to unpack the
      complex psychoemotional and experiential dimensions of casual sex. We report on a
      critical thematic analysis of interviews with 30 ethnically diverse women and men
      (aged 18 to 46) in New Zealand about their experiences of heterosexual casual sex
      to achieve two things. First, we demonstrate the complexity with which women and
      men discussed their casual sex experiences, highlighting how the practice was
      varied, contradictory, and multifaceted, and played in a localized way during the
      conversation. Second, we illustrate how this talk was governed by contemporary
      Western discourses of intimate relationships and the shape of (gendered)
      heterosexuality. We conclude that casual sex research must always consider the
      broader sociocultural context, as well as the interpersonal context, within which
      any sexual relating is situated.

PMID- 27049596
TI  - Testing enhances both encoding and retrieval for both tested and untested items.
AB  - In forward testing effects, taking a test enhances memory for subsequently
      studied material. These effects have been observed for previously studied and
      tested items, a potentially item-specific testing effect, and newly studied
      untested items, a purely generalized testing effect. We directly compared item
      specific and generalized forward testing effects using procedures to separate
      testing benefits due to encoding versus retrieval. Participants studied two lists
      of Swahili-English word pairs, with the second study list containing "new" pairs
      intermixed with the previously studied "old" pairs. Participants completed a
      review phase in which they took a cued-recall test on only the "old" pairs or
      restudied them. In Experiments 1a, 1b, and 2, the review phase was given either
      before or after the second study list. Testing benefited memory to the same
      degree for both "new" and "old" pairs, suggesting that there were no pair
      specific benefits of testing. The larger benefit from testing when review was
      given before rather than after the second study list suggests that the memory
      enhancement was due to both testing-enhanced encoding and testing-enhanced
      retrieval. To better equate generalized testing effects for "new" and "old"
      pairs, Experiment 3 intermixed them in the review phase. A statistically
      significant pair-specific testing effect for "old" items was now observed.
      Overall, these results show that forward testing effects are due to both testing
      enhanced encoding and retrieval effects and that direct, pair-specific forward
      testing benefits are considerably smaller than indirect, generalized forward
      testing benefits.

PMID- 27049598
TI  - How low can dietary greenhouse gas emissions be reduced without impairing
      nutritional adequacy, affordability and acceptability of the diet? A modelling
      study to guide sustainable food choices.
AB  - OBJECTIVE: To assess the compatibility between reduction of diet-related
      greenhouse gas emissions (GHGE) and nutritional adequacy, acceptability and
      affordability dimensions of diet sustainability. DESIGN: Dietary intake,
      nutritional composition, GHGE and prices were combined for 402 foods selected
      among those most consumed by participants of the Individual National Study on
      Food Consumption. Linear programming was used to model diets with stepwise GHGE
      reductions, minimized departure from observed diet and three scenarios of
      nutritional constraints: none (FREE), on macronutrients (MACRO) and for all
      nutrient recommendations (ADEQ). Nutritional quality was assessed using the mean
      adequacy ratio (MAR) and solid energy density (SED). SETTING: France. SUBJECTS:
      Adults (n 1899). RESULTS: In FREE and MACRO scenarios, imposing up to 30 % GHGE
      reduction did not affect the MAR, SED and food group pattern of the observed
      diet, but required substitutions within food groups; higher GHGE reductions
      decreased diet cost, but also nutritional quality, even with constraints on
      macronutrients. Imposing all nutritional recommendations (ADEQ) increased the
      fruits and vegetables quantity, reduced SED and slightly increased diet cost
      without additional modifications induced by the GHGE constraint up to 30 %
      reduction; higher GHGE reductions decreased diet cost but required non-trivial
      dietary shifts from the observed diet. Not all the nutritional recommendations
      could be met for GHGE reductions >=70 %. CONCLUSIONS: Moderate GHGE reductions
      (<=30 %) were compatible with nutritional adequacy and affordability without
      adding major food group shifts to those induced by nutritional recommendations.
      Higher GHGE reductions either impaired nutritional quality, even when
      macronutrient recommendations were imposed, or required non-trivial dietary
      shifts compromising acceptability to reach nutritional adequacy.

PMID- 27049597
TI  - Effective allergen avoidance for reducing exposure to house dust mite allergens
      and improving disease management in adult atopic asthmatics.
AB  - OBJECTIVE: We investigated the best strategy for adult asthmatics to avoid
      exposure to Dermatophagoides group (Der-1) allergens. METHODS: Adult atopic
      asthmatics (n = 111) followed a 32-item checklist for avoiding Der-1 allergen
      exposure. Twenty-five patients were excluded through incomplete sampling; 50
      remaining patients encased their pillows/futons/mattresses in microfine-fiber
      covers, 13 used vacuum cleaners with dust-mite-collection nozzles, and 23 acted
      as non-intervention controls. During August-October 2010 and August-October 2011,
      dust samples were collected in Petri dishes placed in bedrooms for 2 weeks and
      from mattresses/futons by using adhesive tape on one morning. A Der-1 level
      decrease was defined as a mean 2011 Der-1 level of <1 as a ratio of the 2010
      level on tape or Petri dish samples. We analyzed the associations between Der-1
      level change (by ELISA) and % weekly variability in peak expiratory flow (PEF) or
      fraction of exhaled nitric oxide (FeNO) after intervention. RESULTS: Der-1 levels
      decreased significantly in the covers group but not the vacuuming group. FeNO
      levels and PEF variability were unchanged in both groups. In patients whose Petri
      dish or tape samples showed decreased Der-1 levels, the % PEF variability was
      lower in 2011 than in 2010, but FeNO levels were unchanged. Three interventions
      (vacuuming all family members' mattress/futon surfaces at least weekly or after
      exposure of the futons to sunlight, and floor wiping before vacuuming), plus
      using covers, were the most effective management strategy in reducing Der-1
      levels. CONCLUSIONS: This environmental and bedding maintenance program may help
      manage adult atopic asthma.

PMID- 27049599
TI  - Shoulder Electromyography Measurements During Activities of Daily Living and
      Routine Rehabilitation Exercises.
AB  - Study Design Controlled laboratory study. Background The activity of the rotator
      cuff muscles has not previously been measured with indwelling electromyography
      (EMG) comparing ambulation and other movements. Knowledge of the relative
      contribution of these muscles during various tasks may help to guide
      rehabilitation progression. Objective To measure activity of the rotator cuff
      muscles and other shoulder muscles during normal ambulation, shirt and sling
      donning and doffing, and rehabilitation tasks commonly performed after rotator
      cuff surgery. Methods In 28 volunteers (15 men, 13 women; mean age, 32.2 years),
      indwelling EMG activity was measured in the supraspinatus, infraspinatus, teres
      minor, and subscapularis muscles during various tasks; and surface EMG activity
      was measured in the middle deltoid, biceps, and upper trapezius muscles. Results
      Using median EMG activity, in general, donning and doffing a shirt or sling
      recruited the rotator cuff muscles more than the other 7 tasks tested. Self
      ranging motion using pulleys, especially in the scapular plane, was also
      consistently associated with greater recruitment of the shoulder muscles.
      Pendulum exercises, passive range of motion by a physical therapist, and self
      ranging motion with a dowel recruited the shoulder muscles to a lesser extent.
      Conclusion Our results demonstrate that rehabilitation tasks such as pendulum
      exercises, passive range of motion by a physical therapist, and self-ranging
      motion with a dowel show low EMG activity, whereas pulleys in the sagittal plane
      and scapular plane show greater activity. Scapular plane activity was
      consistently higher than sagittal plane activity. Of all the tasks assessed,
      ambulation without a sling and donning and doffing a sling and a shirt
      consistently showed the highest activity. J Orthop Sports Phys Ther
      2016;46(5):375-383. Epub 6 Apr 2016. doi:10.2519/jospt.2016.6090. 

PMID- 27049600
TI  - Lumbar Thrust Manipulation and Exercise for the Treatment of Mechanical Low Back
      Pain in Adolescents: A Case Series.
AB  - Study Design Case series. Background Low back pain (LBP) is an increasing problem
      in health care. The evidence for the use of spinal manipulative therapy to treat
      pediatric patients with LBP is minimal. The treatment of pediatrics with manual
      therapy, particularly spinal manipulation, is controversial within the medical
      community, primarily with respect to adverse events. The purpose of this case
      series was to illustrate the feasibility and safety of lumbar manipulation plus
      exercise in the adolescent population with mechanical LBP. Case Description Three
      patients-a 13-year-old adolescent girl, 15-year-old adolescent girl, and 13-year
      old adolescent boy-were treated in an outpatient physical therapy setting for
      mechanical LBP. All 3 patients were assessed using a lumbar manipulation clinical
      prediction rule and treated with sidelying lumbar manipulation and exercise.
      Outcomes Patients were treated for a total of 10 to 14 visits over a course of 8
      to 9 weeks. Pain (measured by a numeric pain-rating scale) and disability
      (measured by the modified Oswestry Disability Index) improved to 0/10 and 0%,
      respectively, in each patient. No adverse reactions to manipulation were
      reported. Discussion The results of this case series describe the use of lumbar
      thrust manipulation and exercise for the treatment of mechanical LBP in
      adolescents. The positive results indicate that lumbar manipulation may be a safe
      adjunct therapy. Further studies, including randomized controlled trials, are
      needed to determine effectiveness. Level of Evidence Therapy, level 4. J Orthop
      Sports Phys Ther 2016;46(5):391-398. Epub 6 Apr 2016.
      doi:10.2519/jospt.2016.6366. 

PMID- 27049601
TI  - The AtGRXS3/4/5/7/8 glutaredoxin gene cluster on Arabidopsis thaliana chromosome
      4 is coordinately regulated by nitrate and appears to control primary root
      growth.
AB  - Nitrate and ammonium are the 2 most common forms of inorganic nitrogen available
      to plants in the soil. We previously identified a group of class III glutaredoxin
      genes whose expression is strongly upregulated by nitrate, but not ammonium, in
      Arabidopsis thaliana shoots and roots. A reverse genetics approach was used to
      functionally characterize a subset of these nitrate-regulated glutaredoxins, and
      we found that the AtGRXS3,4,5, and 8 genes function as negative regulators of
      primary root growth. AtGRXS3/4/5/8 are arranged in a tandem array on Arabidopsis
      chromosome 4, and these genes show very high levels of sequence similarity.
      Interestingly, there is one additional glutaredoxin, AtGRXS7, in this same gene
      cluster, but this gene was not identified as nitrate-responsive in our previous
      studies. We show here that AtGRXS7 is upregulated by nitrate and shows strong co
      expression with the other glutaredoxins in this gene cluster. Further, AtGRXS7
      was effectively silenced by the RNAi construct used to target AtGRXS3/4/5/8 for
      previous functional analyses. Overall, it appears that the 5 genes in the
      AtGRX3/4/5/7/8 cluster share virtually identical sequences, regulatory patterns,
      and functions, collectively acting to regulate primary root growth in response to
      soil nitrate. 

PMID- 27049602
TI  - Persistent complex bereavement disorder in caregivers of terminally ill patients
      undergoing supportive-expressive treatment: a pilot study.
AB  - BACKGROUND: The proposal of persistent complex bereavement disorder (PCBD) in the
      DSM-V increased the interest on the impact of grief on the psychological health.
      AIMS: Investigating the time course of psychological symptoms, emotional and
      social abilities in caregivers (undergoing or not to supportive-expressive
      treatment) of terminally ill cancer patients from 1 months before loss to 14
      months after it. METHOD: Thirty-three of 60 caregivers were assessed by PG-12,
      HAM-A, HAM-D, TAS-20 and ASQ, at the admission in Hospice, and after 3, 10 and 14
      months from the loss. Twelve caregivers adhered to follow a supportive-expressive
      treatment and 21 caregivers did not. RESULTS: PG-12, anxiety, and depression
      scores decreased in both groups over time. The score of difficulty in identifying
      emotions and confidence with closeness decreased significantly only in the
      treated-group. PG-12 score at T0 was able to predict the DSM V diagnosis of PCBD
      at T3. CONCLUSIONS: Findings showed a decrease of the anxiety, depression,
      security in the attachment style and an increase of the ability to identify
      emotions during the first year after loss in caregivers of terminally ill cancer
      patients. Pre-loss assessment of prolonged grief risk seems useful to predict the
      diagnosis of PCBD 1 year after loss.

PMID- 27049603
TI  - The relationship between physical activity and health status in patients with
      chronic obstructive pulmonary disease following pulmonary rehabilitation.
AB  - AIM: To investigate the relationship between physical activity (PA) and measures
      of health-related quality of life (HRQoL) and hospital admissions in people with
      chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation
      (PR). METHOD: CINAHL, Medline, PubMed, AMED, PsycINFO and Cochrane Library
      (database inception to July 2014) were searched. Relevant outcomes included
      relationships between PA and HRQoL, lung function (forced expiratory volume in
      one second, FEV1) and/or hospital admission. Six quantitative and 11 qualitative
      studies were included and Harden's method of data synthesis in a mixed-methods
      systematic review was applied. RESULTS: Six months following PR, increase
      activity levels was associated with improvement of 62m in 6MWD, 2.31 and 15.55
      points increase in SGRQ and CRDQ total scores, respectively, 1.3% FEV1 and
      reduced dyspnoea. No study reported on hospital admission. Reported relationships
      were facilitated by healthcare professionals, social supporters, motivation and
      encouragement, reduced fear and seeing benefits and hindered by changing physical
      health, environment, lack of motivation, fear and social isolation. CONCLUSION:
      The associations between increased levels of PA and quality of life, respiratory
      function and dyspnoea are largely based on 6MWD and PA questionnaires. Objective
      measurement of free living activity in exercise maintenance phase is required
      along with participants' views. Implications for rehabilitation Pulmonary
      rehabilitation (PR) is a non-therapeutic intervention in which a team of
      multidisciplinary health care professionals use individually tailored supervised
      exercise training, self-management education, psychological and social support to
      optimize the physical and social performance and autonomy of patients with
      chronic respiratory impairment. Initial benefits from PR decline after program
      completion. Clinical guidelines advocate increase exercise and activity in
      sustaining initial benefits of PR. Following PR, increased levels of physical
      activity in people with COPD undertaking exercise maintenance programmes are
      positively related with improvements in exercise capacity, quality of life and
      dyspnoea. Barriers to activity participation in exercise maintenance programmes,
      which need to be overcome, are fear, lack of motivation, environmental factors,
      such as social isolation and changes in physical health. Rehabilitation
      professionals and social supporters can make rehabilitation more long-lasting and
      facilitate people with COPD to participate in activity by motivating and
      encouraging them, reducing their fears and reinforcing the benefits of activity
      participation.

PMID- 27049604
TI  - Negative thermal expansion and magnetostriction in the frustrated spinel
      ZnCr2(Se1-x S x )4 (0  <=  x  <=  0.1).
AB  - The bond-frustrated ZnCr2Se4 displays strong spin-lattice coupling characterized
      by large magnetostriction and negative thermal expansion. Here, we report on
      systematic investigations on the magnetization, heat capacity, thermal expansion
      and magnetostriction of single crystalline ZnCr2(Se1-x S x )4 (0  ?  x  ?  0.1)
      to study the evolution of its spin-lattice coupling with sulfur substitution. We
      show that with increasing sulfur content, the antiferromagnetic ordering is
      gradually replaced by a spin-glass state, the temperature region of the negative
      thermal expansion expands, and the magnetostriction is gradually suppressed.
      These phenomena are explained qualitatively by taking into account the
      enhancement of the antiferromagnetic interactions and bond disorder introduced by
      sulfur substitution. 

PMID- 27049605
TI  - Revista Gaucha de Enfermagem: 40 years disseminating knowledge production.

PMID- 27049606
TI  - Elemental, microstructural, and mechanical characterization of high gold
      orthodontic brackets after intraoral aging.
AB  - The purpose of the present study was to investigate the elemental composition,
      the microstructure, and the selected mechanical properties of high gold
      orthodontic brackets after intraoral aging. Thirty IncognitoTM (3M Unitek, Bad
      Essen, Germany) lingual brackets were studied, 15 brackets as received (control
      group) and 15 brackets retrieved from different patients after orthodontic
      treatment. The surface of the wing area was examined by scanning electron
      microscopy (SEM). Backscattered electron imaging (BEI) was performed, and the
      elemental composition was determined by X-ray EDS analysis (EDX). After
      appropriate metallographic preparation, the mechanical properties tested were
      Martens hardness (HM), indentation modulus (EIT), elastic index (etaIT), and
      Vickers hardness (HV). These properties were determined employing instrumented
      indentation testing (IIT) with a Vickers indenter. The results were statistically
      analyzed by unpaired t-test (alpha=0.05). There were no statistically significant
      differences evidenced in surface morphology and elemental content between the
      control and the experimental group. These two groups of brackets showed no
      statistically significant difference in surface morphology. Moreover, the mean
      values of HM, EIT, etaIT, and HV did not reach statistical significance between
      the groups (p>0.05). Under the limitations of this study, it may be concluded
      that the surface elemental content and microstructure as well as the evaluated
      mechanical properties of the IncognitoTM lingual brackets remain unaffected by
      intraoral aging.

PMID- 27049607
TI  - Development and experimental evaluation of an alarm concept for an integrated
      surgical workstation.
AB  - INTRODUCTION: Alarm conditions of the technical equipment in operating rooms
      represent a prevalent cause for interruptions of surgeons and scrub nurses,
      resulting in an increase of workload and potential reduction of patient safety.
      In this work, an alarm concept for an integrated operating room system based on
      open communication standards is developed and tested. METHODS: In a laboratory
      experiment, the reactions of surgeons were analysed, comparing the displaying of
      alarms on an integrated workstation and on single devices: disruptive effects of
      alarm handling on primary task (ratings of perceived distraction, resumption lag,
      deterioration of speed, accuracy, and prospective memory), efficiency and
      effectiveness of identification of alarms, as well as perceived workload were
      included. RESULTS: The identification of the alarm cause is significantly more
      efficient and effective with the integrated alarm concept. Moreover, a slightly
      lower deterioration of performance of the primary task due to the interruption of
      alarm handling was observed. CONCLUSION: Displaying alarms on an integrated
      workstation supports alarm handling and consequently reduces disruptive effects
      on the primary task. The findings show that even small changes can reduce
      workload in a complex work environment like the operating room, resulting in
      improved patient safety.

PMID- 27049608
TI  - Special Issue Risk management in medical human-machine systems.

PMID- 27049609
TI  - The role of vitamin B1-B2 and plasma lipid profile in intrahepatic cholestasis of
      pregnancy.
AB  - AIM: The present study aimed to determine the levels of total cholesterol,
      triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins
      (HDL), and vitamins B1 and B2 in intrahepatic cholestasis of pregnancy (ICP)
      patients, and to evaluate if these were involved in the pathophysiology of the
      disease. METHODS: The prospective randomized study included 35 pregnant patients
      who were admitted to the Gynecology and Obstetrics Polyclinic, Faculty of
      Medicine at Dicle University and who were diagnosed with ICP (Group 1), and 40
      healthy pregnant women who were admitted in the same period and who had no
      systemic diseases that might complicate the pregnancy during the pregnancy follow
      up (Group 2). Serum lipid levels and vitamins B1 and B2 were determined and
      compared, and statistical comparisons of the groups were made. RESULTS: There was
      no difference between the TG levels of the two groups (P=0.631). Total
      cholesterol, LDL, HDL, and vitamin B1 and B2 levels were higher in Group 1 than
      in Group 2 (P=0.001, P=0.001, P=0.001, P=0.001, and P=0.032, respectively).
      CONCLUSIONS: Increased levels of vitamins B1 and B2 may indicate a need for
      increased energy metabolism at the fetus. So we believe that new studies are
      required, which will be supported by the placental analyses of the pyruvate and
      lactate levels in maternal blood at delivery and fetal cord blood in order to
      develop a better understanding on the fetal effects of energy metabolism.

PMID- 27049610
TI  - Risk factors and outcomes in "well-selected" vaginal breech deliveries: a
      retrospective observational study.
AB  - OBJECTIVE: To assess risk factors for adverse perinatal and neonatal outcomes in
      "well-selected" singleton vaginal breech deliveries at term. METHODS: During the
      time span from January 2008 up to April 2015 a total of 786 singleton term breech
      deliveries with a planned vaginal delivery were identified in a retrospective
      observational study at Helsinki University Central Hospital, Finland. The study's
      end point was a composite of adverse perinatal and neonatal outcomes. Infants
      with an adverse outcome were compared to all spontaneous singleton vaginal breech
      deliveries with normal perinatal and neonatal outcomes. A multivariate logistic
      regression model was used to analyze associations between adverse neonatal
      outcomes and several variables. The secondary outcome was the severe morbidity
      rate according to the criteria of the term breech trial. RESULTS: An adverse
      neonatal outcome was recorded for 38 (4.8%) infants. According to the study the
      second delivery stage lasting <40 min [adjusted odds ratio (aOR): 0.34, 95%
      confidence interval (95% CI): 0.15-0.79] was associated with lower odds and had a
      protective effect against adverse outcomes. Epidural anesthesia (aOR: 2.88, 95%
      CI: 1.08-7.70) was associated with higher adverse outcomes. The incidence rate of
      severe morbidity was 1.3% (10/787). CONCLUSION: Adverse neonatal outcomes in well
      selected breech deliveries are associated with a prolonged second delivery stage
      lasting >40 min and with epidural anesthesia.

PMID- 27049611
TI  - Correlation between markers of DNA and lipid oxidative damage in maternal and
      fetoplacental compartment in the mid-trimester of pregnancy.
AB  - OBJECTIVE: To determine the levels of 8-isoprostane (8-IP) and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) in urine and in amniotic fluid (AF) of pregnant women and
      to assess the correlation between oxidative status in the maternal and fetal
      compartment in the second trimester of pregnancy. METHODS: One hundred and forty
      six women with singleton pregnancies, undergoing amniocentesis at the Department
      of Obstetrics and Gynaecology at the University Medical Centre Ljubljana, were
      prospectively enrolled. AF and maternal urine were collected in the second
      trimester of pregnancy. Paired urinary and AF 8-IP and 8-OHdG were measured and
      evaluated cross-sectionally. RESULTS: 8-IP and 8-OHdG concentrations were higher
      in maternal urine compared to AF and the ratios were 47:1 and 50:1, respectively.
      AF 8-OHdG was very low and in 74% was below the limit of detection (LOD). We
      found a positive correlation between 8-IP in maternal and fetal compartment
      (rho=0.217, P=0.008), which stayed unchanged also after adjustment for possible
      confounding factors. CONCLUSIONS: Oxidative damage to lipids and DNA is also a
      part of physiologic processes during healthy pregnancy. 8-IP and 8-OHdG are
      constantly present in urine and AF. A weak positive correlation between maternal
      and fetal unit suggests a weak reflection of fetal oxidative status in maternal
      urine in the mid-trimester.

PMID- 27049612
TI  - Antenatal corticosteroids: current controversies.

PMID- 27049613
TI  - Evaluation of quantitative fFn test in predicting the risk of preterm birth.
AB  - OBJECTIVE: To evaluate diagnostic accuracy of quantitative fetal fibronectin
      (qfFN) test in predicting preterm birth (PTB) risk <34 weeks' gestation or within
      14 days from testing. We explored the predictive potential of the test in five
      predefined PTB risk categories based on predefined qfFN thresholds (<10, 10-49,
      50-199, 200-499 and >=500 ng/mL). METHODS: Measurement of cervicovaginal qfFN
      with Rapid fFN 10Q System (Hologic) in 126 women with singleton pregnancy (23-33
      weeks' gestation) reporting signs and symptoms indicative of preterm labour
      (PTL). RESULTS: For PTB prediction risk <34 weeks' gestation, sensitivity
      decreased from 100% to 41.7% and specificity increased from 0% to 99.1% with
      increasing fFN thresholds. Positive predictive value (PPV) increased from 9.5% to
      83.3% with increasing qfFN thresholds, while negative predictive value (NPV) was
      higher than 90% among the fFN-predefined categories. Diagnostic accuracy results
      showed an area under a receiving operator characteristic (ROC) curve of 84.5%
      (95% CI, 0.770-0.903). For delivery prediction within 14 days from the testing,
      sensitivity decreased from 100% to 42.8% and specificity increased from 0% to
      100% with increasing fFN thresholds. Diagnostic accuracy determined by the ROC
      curve was 66.1% (95% CI, 0.330-0.902). CONCLUSIONS: The QfFN thresholds of tests
      are a useful tool to distinguish pregnant women for PTB prediction risk <34
      weeks' gestation.

PMID- 27049614
TI  - Neonates of mothers who have had kidney or liver transplantation.

PMID- 27049615
TI  - Biochemical markers of bone turnover in children with clinical bone fragility.
AB  - BACKGROUND: The role of biochemical bone turnover markers (BTMs) in assessing low
      bone mass and monitoring bisphosphonate treatment in pediatric patients with
      clinical bone fragility is not well established. The aim of the study was to
      examine the correlations of BTMs and the bone mineral density (BMD), and evaluate
      the effects of bisphosphonates therapy on BTMs in children with clinical bone
      fragility. METHODS: Clinical data of 115 patients with clinical bone fragility
      (mean age 9.7+/-5.8 years), 102 of whom received bisphosphonates, were studied.
      Serum alkaline phosphatase (ALP), osteocalcin (OC), urine pyridinoline (PD) and
      deoxypyridinoline (DPD), BMD at baseline and subsequent years were analyzed.
      RESULTS: There was a significant negative correlation between urine PD and lumbar
      BMD (slope=-0.29, p<0.001). There were no correlations between BTMs and lumbar
      BMD Z-score. There was a significant positive correlation between serum OC and
      serum ALP, urine PD and DPD (p<0.001). Serum OC, urine PD and DPD index, as
      expressed as measured value/upper limit of normal value for age, decreased during
      the first 3 years of bisphosphonate therapy. CONCLUSIONS: In children with
      clinical bone fragility, BTMs correlated with each other, but not with lumbar BMD
      Z-score. While they were not reliable predictors of degree of low BMD, the bone
      markers showed suppression during bisphosphonate therapy and may be helpful in
      monitoring the response to therapy.

PMID- 27049616
TI  - Relation of fetuin A levels with cardiac, subcutaneous lipid accumulation and
      insulin resistance parameters in Turkish obese children.
AB  - BACKGROUND: Fetuin A is an inhibitor of insulin action and have been found to be
      related with subcutaneous lipid accumulation and insulin resistance. The relation
      of cardiac lipid accumulation, fetuin A and insulin resistance parameters in
      obese children is not well-known. The aim of the study was to evaluate the
      relation of serum fetuin A levels with subcutaneous and cardiac lipid
      accumulation, and insulin resistance parameters in Turkish obese children.
      METHODS: Serum fetuin A levels, cardiac and subcutaneous lipid accumulation
      parameters of 42 obese (10.9+/-2.3 years, 19 female) and 40 control group
      subjects (11.2+/-2.7) were compared. Cardiac lipid accumulation measured by
      subepicardial adipose tissue thickness. Insulin resistance was assessed using
      homeostasis model assessment (HOMA-IR) index. RESULTS: There were significant
      correlations serum fetuin A levels with BMI-SDS, circumferences of waist, hip and
      midarm, SATT and HOMA-IR (r=0.362, p=0.018, r=0.728, p=0.001, r=0.662, p=0.0001,
      r=0.713, p=0.0001, r=0.477, p=0.001, and r=0.330, p=0.038 as, respectively).
      CONCLUSIONS: Fetuin A was correlated well with cardiac and subcutaneous lipid
      accumulation, insulin resistance parameters, which may be related with early
      pathogenetic mechanisms of metabolic obesity complications in children.

PMID- 27049617
TI  - Ascidian bioresources: common and variant chemical compositions and exploitation
      strategy - examples of Halocynthia roretzi, Styela plicata, Ascidia sp. and Ciona
      intestinalis.
AB  - To explore abundant marine ascidian bioresources, four species from two orders
      have been compared in their chemical compositions. After a universal separation
      of the animal body into two fractions, all tunics have been found rich in
      carbohydrate contents, while all inner body tissues are richer in proteins.
      Cellulose is present almost exclusively in the tunics and more in the order
      Stolidobranchia, while more sulfated polysaccharides are present in
      Phlebobranchia species. Almost all proteins are collagens with a high essential
      amino acid index and high delicious amino acid (DAA) content. All fractions also
      have high contents of good-quality fatty acids and trace minerals but low toxic
      element contents, with different sterols and glycosaminoglycans. There are
      species-specific characteristics observed for vanadium accumulation and sterol
      structures which are also meaningful for ascidian chemotaxonomy and resource
      exploitation. It is suggested that in addition to the present utilizations of
      tunics for cellulose production and of some species' inner body tissues as human
      food, one should explore all species' inner body tissues as human foods and all
      tunics as food or animal feed with the contained cellulose as dietary fiber.
      Collagens, sulfated polysaccharides, glycosaminoglycans, sterols and trace
      elements could be explored as byproducts for, e.g. pharmaceutical and chemical
      industries. 

PMID- 27049618
TI  - Structural and evolutionary relationships among RuBisCOs inferred from their
      large and small subunits.
AB  - Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the key enzyme to
      assimilate CO(2) into the biosphere. The nonredundant structural data sets for
      three RuBisCO domain superfamilies, i.e. large subunit C-terminal domain (LSC),
      large subunit N-terminal domain (LSN) and small subunit domain (SS), were
      selected using QR factorization based on the structural alignment with QH as the
      similarity measure. The structural phylogenies were then constructed to
      investigate a possible functional significance of the evolutionary
      diversification. The LSC could have occurred in both bacteria and archaea, and
      has evolved towards increased complexity in both bacteria and eukaryotes with a 4
      helix-2-helix-2-helix bundle being extended into a 5-helix-3-helix-3-helix one at
      the LSC carboxyl-terminus. The structural variations of LSN could have originated
      not only in bacteria with a short coil, but also in eukaryotes with a long one.
      Meanwhile, the SS dendrogram can be contributed to the structural variations at
      the betaA-betaB-loop region. All the structural variations observed in the coil
      regions have influence on catalytic performance or CO(2)/O(2) selectivities of
      RuBisCOs from different species. Such findings provide insights on RuBisCO
      improvements.

PMID- 27049619
TI  - Analysis, detection and quantitation of mixed cryoglobulins in HCV infection:
      brief review and case examples.
AB  - Considering the high incidence of cryoglobulins in hepatitis C virus (HCV)
      infection together with the high worldwide prevalence of HCV infection,
      identification of clinically apparent mixed cryoglobulinemia syndrome is
      increasingly important as most patients who are identified can now be
      successfully treated. Different approaches for the detection, analysis and
      reporting of cryoglobulins have been described and there is a wide variation in
      results reported, ranging from a qualitative "negative" or "positive", to a
      quantitative report including cryoglobulin type and the total protein. Protein
      and immunofixation (IFE) electrophoresis are generally used to identify and
      characterize cryoglobulins, as these methods quantify and phenotype. Here, we
      present a brief review of the literature and demonstrate a case oriented approach
      for identifying mixed cryoglobulinemia from the preanalytical phase, leading up
      to and including the analytical phase with characterization by IFE. Most patients
      with mixed cryoglobulinemia can now be treated with success. Nevertheless, the
      high cost may limit treatment of those with symptoms unless there is laboratory
      evidence for mixed cryoglubulinemia. Low levels of cryoglobulins can be
      associated with severe symptoms; as a result, accurate identification of
      cryoglobulins may be of increasing importance since clear identification may be a
      good reason to initiate treatment.

PMID- 27049620
TI  - Quality of reporting of diagnostic test accuracy studies in medical laboratory
      journals.

PMID- 27049621
TI  - Meeting the Growing Need for Heroin Addiction Treatment.

PMID- 27049622
TI  - New portable voice guidance device for the manual wheelchair transfer: a pilot
      study in patients with hemiplegia.
AB  - PURPOSE: Older and/or cognitively impaired patients require verbal guidance to
      prevent accidents during wheelchair operation, thus increasing the burden on
      caregivers. This study aimed to develop a new portable voice guidance device for
      manual wheelchairs and examine its clinical usefulness. METHOD: We developed a
      portable voice guidance device to monitor the statuses of wheelchair brakes and
      footrests and automatically provide voice guidance for operation. The device
      comprises a microcomputer, four magnets and magnetic sensors, speaker and
      battery. Device operation was assessed during the transfer from a wheelchair to
      bed six times per day over three days for a total of 90 transfers in five stroke
      patients (mean age: 79.6 years) who required verbal guidance to direct wheelchair
      operation. Device usability was also assessed using a questionnaire. RESULTS: The
      device performed perfectly during all attempted transfers (100%). To ensure
      safety, the assessor needed to add verbal guidance during 33 of 90 attempted
      transfers (36.6%). Overall, the device usability was favourable. However, some
      assessors were unsatisfied with the volume of the device voice, guidance timing
      and burden reduction. CONCLUSIONS: Our device could facilitate wheelchair
      operation and might potentially be used to reduce fall risk in stroke patients
      and the burden on caregivers. Implications for Rehabilitation The acquisition of
      transfer independence is an important step in the rehabilitation of patients with
      mobility issues. Many patients require supervision and guidance regarding the
      operation of brakes and footrests on manual wheelchairs. This newly developed
      voice guidance device for manual wheelchair transfers worked well in patients
      with hemiplegia and might be helpful to reduce the fall risks and the burden of
      care.

PMID- 27049625
TI  - An Analysis of the Daily Work-Rounding Process in a Pediatric Intensive Care
      Unit.
AB  - OBJECTIVE: To complete an objective analysis of the activities that occur during
      the course of daily rounds in a high acuity academic tertiary care pediatric
      intensive care unit (PICU). DESIGN: Prospective observational work sampling
      design. SETTING: Tertiary care academic Children's Hospital Pediatric Intensive
      Care Unit. SUBJECTS: Multidisciplinary PICU teams. INTERVENTIONS: None. METHODS:
      Intensive care unit rounds were observed as part of an initiative to improve
      efficiency over a 2-month period. The number of observations required was
      determined by Neibel's work sampling method. Rounds were broken into various
      constituent events and then later classified as "value-added/essential," "value
      added/nonessential," and "nonessential" based on whether the observed event was
      essential to the core mission of PICU rounds. RESULTS: The mean time spent per
      patient for all observed teams was 17.9 min (SD 1.3 min). Teams spent 64% of
      their time doing value-added/essential tasks (11.2 min, SD 2.2 min) and 13% of
      their time doing value-added/nonessential tasks (2.4 min, SD 0.9 min). Teams
      spent 23% of their time on non-value-added activities (4.1 min, SD 2.3 min). The
      top three non-value-added activities conducted during rounds were travel,
      waiting, and interruptions regarding care of other patients. Given the
      consistency of time spent on value-added activities among attendings, these non
      value-added activities might explain the significant variability observed among
      attendings in total time spent rounding. CONCLUSIONS: This was an observational
      study to characterize the activities that occur during the course of a routine
      PICU work rounds. Although there was significant consistency in the time spent
      per patient in value-added activities, there was significant disparity in time
      spent on nonessential activities, such as travel and waiting. A dedicated attempt
      to reduce time spent on nonessential activities can substantially reduce rounding
      times and improve the efficiency and value of rounds.

PMID- 27049626
TI  - Measuring Chemotherapy Appointment Duration and Variation Using Real-Time
      Location Systems.
AB  - INTRODUCTION: Clinical schedules drive resource utilization, cost, and patient
      wait time. Accurate appointment duration allocation ensures appropriate staffing
      ratios to daily caseloads and maximizes scarce resources. Dana-Farber Cancer
      Institute (DFCI) infusion appointment duration is adjusted by regimen using a
      consensus method of experts including pharmacists, nurses, and administrators.
      Using real-time location system (RTLS), we examined the accuracy of observed
      appointment duration compared with the scheduled duration. METHODS: Appointment
      duration was calculated using RTLS at DFCI between August 1, 2013, and September
      30, 2013. Duration was defined as the total time a patient occupied an infusion
      chair. The top 10 administered infusion regimens were investigated (n = 805).
      RESULTS: Median observed appointment durations were statistically different than
      the scheduled durations. Appointment durations were shorter than scheduled 98%
      (C), 95% (I), and 75% (F) of the time and longer than scheduled 77% (A) and 76%
      (G) of the time. Fifty-six percent of the longer than scheduled (A) appointments
      were at least 30 minute longer. CONCLUSION: RTLS provides reliable and unbiased
      data to improve schedule accuracy. Replacing consensus with system-based data may
      improve clinic flow, relieve staff stress, and increase patient satisfaction.
      Further investigation is warranted to elucidate factors that impact variation in
      appointment duration.

PMID- 27049627
TI  - Fibro-fog.

PMID- 27049628
TI  - Mass Spectrometry Applied to Bottom-Up Proteomics: Entering the High-Throughput
      Era for Hypothesis Testing.
AB  - Proteins constitute a key class of molecular components that perform essential
      biochemical reactions in living cells. Whether the aim is to extensively
      characterize a given protein or to perform high-throughput qualitative and
      quantitative analysis of the proteome content of a sample, liquid chromatography
      coupled to tandem mass spectrometry has become the technology of choice. In this
      review, we summarize the current state of mass spectrometry applied to bottom-up
      proteomics, the approach that focuses on analyzing peptides obtained from
      proteolytic digestion of proteins. With the recent advances in instrumentation
      and methodology, we show that the field is moving away from providing qualitative
      identification of long lists of proteins to delivering highly consistent and
      accurate quantification values for large numbers of proteins across large numbers
      of samples. We believe that this shift will have a profound impact for the field
      of proteomics and life science research in general.

PMID- 27049629
TI  - Applications of Optical Microcavity Resonators in Analytical Chemistry.
AB  - Optical resonator sensors are an emerging class of analytical technologies that
      use recirculating light confined within a microcavity to sensitively measure the
      surrounding environment. Bolstered by advances in microfabrication, these devices
      can be configured for a wide variety of chemical or biomolecular sensing
      applications. We begin with a brief description of optical resonator sensor
      operation, followed by discussions regarding sensor design, including different
      geometries, choices of material systems, methods of sensor interrogation, and new
      approaches to sensor operation. Throughout, key developments are highlighted,
      including advancements in biosensing and other applications of optical sensors.
      We discuss the potential of alternative sensing mechanisms and hybrid sensing
      devices for more sensitive and rapid analyses. We conclude with our perspective
      on the future of optical microcavity sensors and their promise as versatile
      detection elements within analytical chemistry. 

PMID- 27049630
TI  - Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection.
AB  - Recent advances in magnetic resonance imaging (MRI) contrast agents have provided
      new capabilities for biomarker detection through molecular imaging. MRI contrast
      agents based on the T2 exchange mechanism have more recently expanded the
      armamentarium of agents for molecular imaging. Compared with T1 and T2* agents,
      T2 exchange agents have a slower chemical exchange rate, which improves the
      ability to design these MRI contrast agents with greater specificity for
      detecting the intended biomarker. MRI contrast agents that are detected through
      chemical exchange saturation transfer (CEST) have even slower chemical exchange
      rates. Another emerging class of MRI contrast agents uses hyperpolarized (13)C to
      detect the agent with outstanding sensitivity. These hyperpolarized (13)C agents
      can be used to track metabolism and monitor characteristics of the tissue
      microenvironment. Together, these various MRI contrast agents provide excellent
      opportunities to develop molecular imaging for biomarker detection.

PMID- 27049632
TI  - Plant Molecular Farming: Much More than Medicines.
AB  - Plants have emerged as commercially relevant production systems for
      pharmaceutical and nonpharmaceutical products. Currently, the commercially
      available nonpharmaceutical products outnumber the medical products of plant
      molecular farming, reflecting the shorter development times and lower regulatory
      burden of the former. Nonpharmaceutical products benefit more from the low costs
      and greater scalability of plant production systems without incurring the high
      costs associated with downstream processing and purification of pharmaceuticals.
      In this review, we explore the areas where plant-based manufacturing can make the
      greatest impact, focusing on commercialized products such as antibodies, enzymes,
      and growth factors that are used as research-grade or diagnostic reagents,
      cosmetic ingredients, and biosensors or biocatalysts. An outlook is provided on
      high-volume, low-margin proteins such as industrial enzymes that can be applied
      as crude extracts or unprocessed plant tissues in the feed, biofuel, and
      papermaking industries.

PMID- 27049633
TI  - Molecular Plasmonics.
AB  - In this review, we survey recent advances in the field of molecular plasmonics
      beyond the traditional sensing modality. Molecular plasmonics is explored in the
      context of the complex interaction between plasmon resonances and molecules and
      the ability of molecules to support plasmons self-consistently. First,
      spectroscopic changes induced by the interaction between molecular and plasmonic
      resonances are discussed, followed by examples of how tuning molecular properties
      leads to active molecular plasmonic systems. Next, the role of the position and
      polarizability of a molecular adsorbate on surface-enhanced Raman scattering
      signals is examined experimentally and theoretically. Finally, we introduce
      recent research focused on using molecules as plasmonic materials. Each of these
      examples is intended to highlight the role of molecules as integral components in
      coupled molecule-plasmon systems, as well as to show the diversity of
      applications in molecular plasmonics. 

PMID- 27049634
TI  - Electroanalytical Ventures at Nanoscale Interfaces Between Immiscible Liquids.
AB  - Ion transfer at the interface between immiscible electrolyte solutions offers
      many benefits to analytical chemistry, including the ability to detect nonredox
      active ionized analytes, to detect ions whose redox electrochemistry is
      accompanied by complications, and to separate ions based on electrocontrolled
      partition. Nanoscale miniaturization of such interfaces brings the benefits of
      enhanced mass transport, which in turn leads to improved analytical performance
      in areas such as sensitivity and limits of detection. This review discusses the
      development of such nanoscale interfaces between immiscible liquids and examines
      the analytical advances that have been made to date, including prospects for
      trace detection of ion concentrations. 

PMID- 27049631
TI  - Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to
      Characterize Human Proteomic Variation.
AB  - Mass spectrometry-based proteomics has emerged as the leading method for
      detection, quantification, and characterization of proteins. Nearly all proteomic
      workflows rely on proteomic databases to identify peptides and proteins, but
      these databases typically contain a generic set of proteins that lack variations
      unique to a given sample, precluding their detection. Fortunately, proteogenomics
      enables the detection of such proteomic variations and can be defined, broadly,
      as the use of nucleotide sequences to generate candidate protein sequences for
      mass spectrometry database searching. Proteogenomics is experiencing heightened
      significance due to two developments: (a) advances in DNA sequencing technologies
      that have made complete sequencing of human genomes and transcriptomes routine,
      and (b) the unveiling of the tremendous complexity of the human proteome as
      expressed at the levels of genes, cells, tissues, individuals, and populations.
      We review here the field of human proteogenomics, with an emphasis on its
      history, current implementations, the types of proteomic variations it reveals,
      and several important applications.

PMID- 27049635
TI  - New Functionalities for Paper-Based Sensors Lead to Simplified User Operation,
      Lower Limits of Detection, and New Applications.
AB  - In the last decade, paper analytical devices (PADs) have evolved into
      sophisticated yet simple sensors with biological and environmental applications
      in the developed and developing world. The focus of this review is the
      technological improvements that have over the past five years increased the
      applicability of PADs to real-world problems. Specifically, this review reports
      on advances in sample processing, fluid flow control, signal amplification, and
      component integration. Throughout, we have sought to emphasize advances that
      retain the main virtues of PADs: low cost, portability, and simplicity. 

PMID- 27049636
TI  - Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling
      Networks.
AB  - Protein phosphorylation-mediated cellular signaling networks regulate almost all
      aspects of cell biology, including the responses to cellular stimulation and
      environmental alterations. These networks are highly complex and comprise
      hundreds of proteins and potentially thousands of phosphorylation sites. Multiple
      analytical methods have been developed over the past several decades to identify
      proteins and protein phosphorylation sites regulating cellular signaling, and to
      quantify the dynamic response of these sites to different cellular stimulation.
      Here we provide an overview of these methods, including the fundamental
      principles governing each method, their relative strengths and weaknesses, and
      some examples of how each method has been applied to the analysis of complex
      signaling networks. When applied correctly, each of these techniques can provide
      insight into the topology, dynamics, and regulation of protein phosphorylation
      signaling networks.

PMID- 27049637
TI  - On the ClC halogen bond: a rotational study of CF3Cl-CO.
AB  - The rotational spectra of two isotopologues (CF3(35)Cl-CO and CF3(37)Cl-CO) of
      the CF3Cl-CO adduct have been investigated and analyzed using supersonic-jet
      Fourier transform microwave spectroscopy, and found to have the features of a
      symmetric top. Rotational, centrifugal distortion, and nuclear quadrupole ((35)Cl
      and (37)Cl) coupling constants have been precisely obtained from high-resolution
      measurements. The two subunits of the complex are held together via a ClC halogen
      bond interaction. Information on the internal dynamics and the dissociation
      energy of the complex is provided. 

PMID- 27049638
TI  - Gender differences in giant cell arteritis: a case-control study.
AB  - OBJECTIVES: To determine sex differences in the clinical spectrum and disease
      pattern of cranial and extracranial giant cell arteritis (GCA). METHODS: Data on
      153 consecutive patients with a confirmed diagnosis of GCA between 2002 and 2013
      were retrospectively obtained from our database. For every male patient, two age
      matched female patients were identified. Clinical symptoms, vascular physical
      examination findings, laboratory values, and the disease patterns as assessed by
      colour duplex sonography of the temporal and axillary arteries were compared
      between women and men. Subgroup analyses were performed for patients aged 50-69
      years and >=70 years at disease onset. RESULTS: No significant differences
      between sexes were noted with regard to cranial GCA. Female patients
      significantly more frequently had axillary artery involvement (48.9 vs. 27.5%,
      p=0.03), a difference mainly driven by a higher rate of axillary artery
      involvement in women >=70 years of age (38.6 vs. 4.5%, p<0.01). Women aged 70
      years or older significantly more frequently had axillary artery stenosis (27.3
      vs. 0%, p<0.01), symptoms of upper extremity ischaemia (20.5 vs. 0%, p<0.01), and
      polymyalgia rheumatica (36.4 vs. 9.1%, p=0.02) compared to men. Significant sex
      differences were observed with regard to the frequency of anaemia and the mean
      platelet count. CONCLUSIONS: In GCA involvement of the cranial arteries does not
      differ between sexes. Female patients with GCA significantly more frequently
      exhibit extracranial (i.e. axillary) arterial involvement than men.

PMID- 27049639
TI  - Self-supported Zn3P2 nanowire arrays grafted on carbon fabrics as an advanced
      integrated anode for flexible lithium ion batteries.
AB  - We, for the first time, successfully grafted well-aligned binary lithium-reactive
      zinc phosphide (Zn3P2) nanowire arrays on carbon fabric cloth by a facile CVD
      method. When applied as a novel self-supported binder-free anode for lithium ion
      batteries (LIBs), the hierarchical three-dimensional (3D) integrated anode shows
      excellent electrochemical performances: a highly reversible initial lithium
      storage capacity of ca. 1200 mA h g(-1) with a coulombic efficiency of up to 88%,
      a long lifespan of over 200 cycles without obvious decay, and a high rate
      capability of ca. 400 mA h g(-1) capacity retention at an ultrahigh rate of 15 A
      g(-1). More interestingly, a flexible LIB full cell is assembled based on the as
      synthesized integrated anode and the commercial LiFePO4 cathode, and shows
      striking lithium storage performances very close to the half cells: a large
      reversible capacity over 1000 mA h g(-1), a long cycle life of over 200 cycles
      without obvious decay, and an ultrahigh rate performance of ca. 300 mA h g(-1)
      even at 20 A g(-1). Considering the excellent lithium storage performances of
      coin-type half cells as well as flexible full cells, the as-prepared carbon cloth
      grafted well-aligned Zn3P2 nanowire arrays would be a promising integrated anode
      for flexible LIB full cell devices. 

PMID- 27049640
TI  - Contributions of Phenoxazone-Based Pigments to the Structure and Function of
      Nanostructured Granules in Squid Chromatophores.
AB  - Understanding the structure-function relationships of pigment-based
      nanostructures can provide insight into the molecular mechanisms behind
      biological signaling, camouflage, or communication experienced in many species.
      In squid Doryteuthis pealeii, combinations of phenoxazone-based pigments are
      identified as the source of visible color within the nanostructured granules that
      populate dermal chromatophore organs. In the absence of the pigments, granules
      experience a reduction in diameter with the loss of visible color, suggesting
      important structural and functional features. Energy gaps are estimated from
      electronic absorption spectra, revealing highest occupied molecular orbital
      (HOMO)-lowest unoccupied molecular orbital (LUMO) energies that are dependent
      upon the varying carboxylated states of the pigment. These results implicate a
      hierarchical mechanism for the bulk coloration in cephalopods originating from
      the molecular components confined within in the nanostructured granules of
      chromatophore organs. 

PMID- 27049641
TI  - A biomimetic colorimetric logic gate system based on multi-functional peptide
      mediated gold nanoparticle assembly.
AB  - In natural biological systems, proteins exploit various functional peptide motifs
      to exert target response and activity switch, providing a functional and logic
      basis for complex cellular activities. Building biomimetic peptide-based bio
      logic systems is highly intriguing but remains relatively unexplored due to
      limited logic recognition elements and complex signal outputs. In this proof-of
      principle work, we attempted to address these problems by utilizing multi
      functional peptide probes and the peptide-mediated nanoparticle assembly system.
      Here, the rationally designed peptide probes function as the dual-target
      responsive element specifically responsive to metal ions and enzymes as well as
      the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking
      advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and
      enzymes, respectively, we constructed the peptide logic system computed by the
      multi-functional peptide probes and outputted by the readable colour change of
      AuNPs. In this way, the representative binary basic logic gates (AND, OR,
      INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide
      sequence, demonstrating the versatility of our logic system. Additionally, we
      demonstrated that the three-input combinational logic gate (INHIBIT-OR) could
      also be successfully integrated and applied as a multi-tasking biosensor for
      colorimetric detection of dual targets. This nanoparticle-based peptide logic
      system presents a valid strategy to illustrate peptide information processing and
      provides a practical platform for executing peptide computing or peptide-related
      multiplexing sensing, implying that the controllable nanomaterial assembly is a
      promising and potent methodology for the advancement of biomimetic bio-logic
      computation.

PMID- 27049642
TI  - Efficient Temperature-Dependent Green's Function Methods for Realistic Systems:
      Using Cubic Spline Interpolation to Approximate Matsubara Green's Functions.
AB  - The popular, stable, robust, and computationally inexpensive cubic spline
      interpolation algorithm is adopted and used for finite temperature Green's
      function calculations of realistic systems. We demonstrate that with appropriate
      modifications the temperature dependence can be preserved while the Green's
      function grid size can be reduced by about 2 orders of magnitude by replacing the
      standard Matsubara frequency grid with a sparser grid and a set of interpolation
      coefficients. We benchmarked the accuracy of our algorithm as a function of a
      single parameter sensitive to the shape of the Green's function. Through numerous
      examples, we confirmed that our algorithm can be utilized in a systematically
      improvable, controlled, and black-box manner and highly accurate one- and two
      body energies and one-particle density matrices can be obtained using only around
      5% of the original grid points. Additionally, we established that to improve
      accuracy by an order of magnitude, the number of grid points needs to be doubled,
      whereas for the Matsubara frequency grid, an order of magnitude more grid points
      must be used. This suggests that realistic calculations with large basis sets
      that were previously out of reach because they required enormous grid sizes may
      now become feasible. 

PMID- 27049643
TI  - Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation:
      Cross-Sectional and Interventional Findings.
AB  - OBJECTIVES: Understanding of the influence of vitamin D deficiency on epigenome
      will provide novel insights into the chronic disease risk. We tested our
      hypotheses that 1) vitamin D deficiency is associated with global hypomethylation
      and this association may be race/ethnicity dependent; and 2) vitamin D
      supplementation will increase global DNA methylation level. METHODS: A two-stage
      design, cross-sectional observation followed by a 16 week randomized, double-
      blinded, placebo-controlled trial (RCT) of vitamin D3 supplementation, was
      undertaken. Global DNA methylation level (percentage of 5-methylcytosine, %5-mC)
      was quantified using leukocyte DNA with the MethylFlashTM Methylated DNA
      Quantification kit (Epigentek). Global methylation data was obtained from 454
      Caucasians and African Americans (42%) in the observation cohort and 58 African
      Americans with vitamin D deficiency in the dose responsive RCT. RESULTS: In the
      cross-sectional study, African Americans had lower %5-mC than Caucasians (P =
      0.04). A significant interaction was detected between plasma 25(OH)D and race on
      %5-mC (P = 0.05), as a positive association was observed between plasma 25(OH)D
      and %5-mC in African Americans (beta = 0.20, p<0.01), but not in Caucasians (beta
      = 0.03, p = 0.62). In the 16-week RCT, a dose-response benefit of vitamin D3
      supplementation was observed for %5-mC, as indicated by a significant linear
      upward trend (-0.01 +/- 0.01%, placebo; 0.11 +/- 0.01%, ~600 IU/day; 0.30 +/-
      0.01%, ~2,000 IU/day; and 0.65 +/- 0.01%, ~4,000 IU/day group; P-trend = 0.04).
      CONCLUSIONS: Vitamin D deficiency is associated with global hypomethylation in
      African Americans. Vitamin D3 supplementation increases global DNA methylation in
      a dose-response manner in African Americans with vitamin D deficiency.

PMID- 27049644
TI  - Ranging, Activity and Habitat Use by Tigers in the Mangrove Forests of the
      Sundarban.
AB  - The Sundarban of India and Bangladesh (about 6000 km2) are the only mangrove
      forests inhabited by a sizeable population of tigers. The adjoining area also
      supports one of the highest human densities and experiences severe human-tiger
      conflicts. We used GPS-Satellite and VHF radio-collars on 6 (3 males and 3
      female) tigers to study their ranging patterns and habitat preference. The
      average home range (95% Fixed Kernel) for resident females was 56.4 (SE 5.69) and
      for males it was 110 (SE 49) km2. Tigers crossed an average of 5 water channels >
      30 meters per day with a mean width of 54 meters, whereas channels larger than
      400 meters were rarely crossed. Tigers spent over 58% of their time within
      Phoenix habitat but compositional analysis showed a habitat preference of the
      order Avicennia-Sonneratia > Phoenix > Ceriops > Barren > Water. Average daily
      distance moved was 4.6 km (range 0.1-23). Activity of tigers peaked between 05:00
      hours and 10:00 hours showing some overlap with human activity. Territory
      boundaries were demarcated by large channels which tigers intensively patrolled.
      Extra caution should be taken while fishing or honey collection during early
      morning in Avicennia-Sonneratia and Phoenix habitat types along wide channels to
      reduce human-tiger conflict. Considering home-range core areas as exclusive,
      tiger density was estimated at 4.6 (SE range 3.6 to 6.7) tigers/100 km2 giving a
      total population of 76 (SE range 59-110) tigers in the Indian Sundarban.
      Reluctance of tigers to cross wide water channels combined with increasing
      commercial boat traffic and sea level rise due to climate change pose a real
      threat of fragmenting the Sundarban tiger population. 

PMID- 27049645
TI  - Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease
      Sensitive Toxin Nanocapsules.
AB  - Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels;
      however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The
      silent provirus can be activated through the use of drugs, including protein
      kinase C activators and histone deacetylase inhibitors. This "shock" approach is
      then followed by "kill" of the producing cells either through direct HIV-1
      induced cell death or natural immune mechanisms. However, these mechanisms are
      relatively slow and effectiveness is unclear. Here, we develop an approach to
      specifically target and kill cells that are activated early in the process of
      virus production. We utilize a novel nanocapsule technology whereby the ricin A
      chain is encapsulated in an inactive form within a polymer shell. Specificity for
      release of the ricin A toxin is conferred by peptide crosslinkers that are
      sensitive to cleavage by HIV-1 protease. By using well-established latent
      infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1
      producing cell expressing functional HIV-1 protease will the nanocapsule release
      its ricin A cargo, shutting down viral and cellular protein synthesis, and
      ultimately leading to rapid death of the producer cell. Thus, we provide proof of
      principle for a novel technology to kill HIV-1-producing cells without effects on
      non-target cells. 

PMID- 27049646
TI  - Preparation of High-Efficiency Cytochrome c-Imprinted Polymer on the Surface of
      Magnetic Carbon Nanotubes by Epitope Approach via Metal Chelation and Six
      Membered Ring.
AB  - A novel epitope molecularly imprinted polymer on the surface of magnetic carbon
      nanotubes (MCNTs@EMIP) was successfully fabricated to specifically recognize
      target protein cytochrome c (Cyt C) with high performance. The peptides sequences
      corresponding to the surface-exposed C-terminus domains of Cyt C was selected as
      epitope template molecule, and commercially available zinc acrylate and ethylene
      glycol dimethacrylate (EGDMA) were employed as functional monomer and cross
      linker, respectively, to synthesize MIP via free radical polymerization. The
      epitope was immobilized via metal chelation and six-membered ring formed between
      the functional monomer and the hydroxyl and amino groups of the epitope. The
      resulting MCNTs@EMIP exhibited specific recognition ability toward target Cyt C
      including more satisfactory imprinting factor (about 11.7) than that of other
      reported imprinting methods. In addition, the MCNTs@EMIP demonstrated a high
      adsorption amount (about 780.0 mg g(-1)) and excellent selectivity. Besides, the
      magnetic property of the support material made the processes easy and highly
      efficient by assistance of an external magnetic field. High-performance liquid
      chromatography analysis of Cyt C in bovine blood real sample and protein mixture
      indicated that the specificity was not affected by other competitive proteins,
      which forcefully stated that the MCNTs@EMIP had potential to be applied in
      bioseparation area. In brief, this study provided a new protocol to detect target
      protein in complex sample via epitope imprinting approach and surface imprinting
      strategy.

PMID- 27049647
TI  - Macular Ganglion Cell Analysis Determined by Cirrus HD Optical Coherence
      Tomography for Early Detecting Chiasmal Compression.
AB  - PURPOSE: To evaluate the performance of macular ganglion cell-inner plexiform
      layer (mGCIPL) measurement with Cirrus high-definition (HD) optical coherence
      tomography (OCT) for early detection of optic chiasmal compression. METHODS:
      Forty-six eyes of 46 patients with optic chiasmal compression caused by a
      pituitary adenoma (PA group), 31 eyes of 31 patients with normal tension glaucoma
      (NTG group), and 32 eyes of 32 normal participants (control group) were enrolled.
      The PA group was subdivided into two subgroups, which comprised patients with
      temporal visual field (VF) defects (perimetric PA group, 34 eyes) and without VF
      defect (preperimetric PA group, 12 eyes). The mGCIPL thickness and
      circumpapillary retinal nerve fiber layer (cpRNFL) thickness were measured using
      Cirrus HD-OCT. We calculated the number of patients who had an abnormal GCA
      sector map, defined as at least one yellow or red sector. RESULTS: Eyes in the
      perimetric PA group had significantly decreased mGCIPL thickness in all sectors.
      Eyes in the preperimetric PA group had significantly thinner mGCIPL in the
      superior, superonasal, inferonasal, and inferior sectors than eyes in control
      group, but no changes in cpRNFL parameters were observed. The mGCIPL thickness in
      inferonasal area showed the greatest AUC value (0.965), followed by the
      superonasal area (0.958) for discriminating preperimetric PA group from the
      control group. A higher reduction rate of mGCIPL thickness was noted in the nasal
      sector compared to other sectors, which was irrespective of temporal visual field
      defects. The mGCIPL thickness maps showed superonasal (P = 0.003) and inferonasal
      thinning in the PA group (P = 0.003), while inferotemporal thinning was revealed
      in the NTG group (P = 0.001). CONCLUSIONS: Macular GCIPL thickness parameters
      obtained with the Cirrus HD-OCT were useful in early detection of chiasmal
      compression and differentiating from NTG by characteristic nasal mGCIPL thinning.

PMID- 27049648
TI  - Effect of noise on comfort in open-plan offices: application of an assessment
      questionnaire.
AB  - Open-plan offices account for 60% of French office workspaces. The noise levels
      recorded in this type of environment are much lower than those encountered in
      industrial workplaces. Nevertheless, surveys show that noise is considered by
      employees as the main source of discomfort. A first questionnaire dedicated to
      noise discomfort was produced in 2013 and tested on a panel made up of 217 people
      working in 7 French companies. Today, it also makes it possible to address the
      issues of fatigue related to ambient sound, but above all, the survey aims to
      study the differences in how ambient noise is perceived depending on the type of
      open-plan office. On the basis of that new version, a second survey has been
      conducted in 23 open-plan offices, making it possible to collect the responses
      from 617 employees. Most of the results of the first survey have been confirmed,
      with an increase in the significance of the statistical analyses. Moreover,
      French Standard NF S 31-199, which is currently being drafted, establishes a
      typology of open-plan office spaces according to the types of work done in them.
      Based on this typology, it appears that when dealing with the impact on noise on
      workers, a distinction has to be made between the types of open plan offices.
      Practitioner Summary: Surveys conducted in open-plan offices show that noise is
      considered by employees as the main source of discomfort even if the noise
      recorded in this type of environment is not hazardous. This work presents the
      result of a large survey dedicated to noise discomfort conducted in 23 open-plan
      offices.

PMID- 27049649
TI  - Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase
      regulatory domain.
AB  - The multi-domain enzyme phenylalanine hydroxylase (PAH) catalyzes the
      hydroxylation of dietary I-phenylalanine (Phe) to I-tyrosine. Inherited mutations
      that result in PAH enzyme deficiency are the genetic cause of the autosomal
      recessive disorder phenylketonuria. Phe is the substrate for the PAH active site,
      but also an allosteric ligand that increases enzyme activity. Phe has been
      proposed to bind, in addition to the catalytic domain, a site at the PAH N
      terminal regulatory domain (PAH-RD), to activate the enzyme via an unclear
      mechanism. Here we report the crystal structure of human PAH-RD bound with Phe at
      1.8 A resolution, revealing a homodimer of ACT folds with Phe bound at the dimer
      interface. This work delivers the structural evidence to support previous
      solution studies that a binding site exists in the RD for Phe, and that Phe
      binding results in dimerization of PAH-RD. Consistent with our structural
      observation, a disease-associated PAH mutant impaired in Phe binding disrupts the
      monomer:dimer equilibrium of PAH-RD. Our data therefore support an emerging model
      of PAH allosteric regulation, whereby Phe binds to PAH-RD and mediates the
      dimerization of regulatory modules that would bring about conformational changes
      to activate the enzyme.

PMID- 27049650
TI  - Recruitment Variability of Coral Reef Sessile Communities of the Far North Great
      Barrier Reef.
AB  - One of the key components in assessing marine sessile organism demography is
      determining recruitment patterns to benthic habitats. An analysis of serially
      deployed recruitment tiles across depth (6 and 12 m), seasons (summer and winter)
      and space (meters to kilometres) was used to quantify recruitment assemblage
      structure (abundance and percent cover) of corals, sponges, ascidians, algae and
      other sessile organisms from the northern sector of the Great Barrier Reef (GBR).
      Polychaetes were most abundant on recruitment titles, reaching almost 50% of
      total recruitment, yet covered <5% of each tile. In contrast, mean abundances of
      sponges, ascidians, algae, and bryozoans combined was generally less than 20% of
      total recruitment, with percentage cover ranging between 15-30% per tile. Coral
      recruitment was very low, with <1 recruit per tile identified. A hierarchal
      analysis of variation over a range of spatial and temporal scales showed
      significant spatio-temporal variation in recruitment patterns, but the highest
      variability occurred at the lowest spatial scale examined (1 m-among tiles).
      Temporal variability in recruitment of both numbers of taxa and percentage cover
      was also evident across both summer and winter. Recruitment across depth varied
      for some taxonomic groups like algae, sponges and ascidians, with greatest
      differences in summer. This study presents some of the first data on benthic
      recruitment within the northern GBR and provides a greater understanding of
      population ecology for coral reefs. 

PMID- 27049651
TI  - Predicting Survival from Telomere Length versus Conventional Predictors: A
      Multinational Population-Based Cohort Study.
AB  - Telomere length has generated substantial interest as a potential predictor of
      aging-related diseases and mortality. Some studies have reported significant
      associations, but few have tested its ability to discriminate between decedents
      and survivors compared with a broad range of well-established predictors that
      include both biomarkers and commonly collected self-reported data. Our aim here
      was to quantify the prognostic value of leukocyte telomere length relative to
      age, sex, and 19 other variables for predicting five-year mortality among older
      persons in three countries. We used data from nationally representative surveys
      in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N =
      2672, aged 60+). Our study used a prospective cohort design with all-cause
      mortality during five years post-exam as the outcome. We fit Cox hazards models
      separately by country, and assessed the discriminatory ability of each predictor.
      Age was, by far, the single best predictor of all-cause mortality, whereas
      leukocyte telomere length was only somewhat better than random chance in terms of
      discriminating between decedents and survivors. After adjustment for age and sex,
      telomere length ranked between 15th and 17th (out of 20), and its incremental
      contribution was small; nine self-reported variables (e.g., mobility, global self
      assessed health status, limitations with activities of daily living, smoking
      status), a cognitive assessment, and three biological markers (C-reactive
      protein, serum creatinine, and glycosylated hemoglobin) were more powerful
      predictors of mortality in all three countries. Results were similar for cause
      specific models (i.e., mortality from cardiovascular disease, cancer, and all
      other causes combined). Leukocyte telomere length had a statistically
      discernible, but weak, association with mortality, but it did not predict
      survival as well as age or many other self-reported variables. Although telomere
      length may eventually help scientists understand aging, more powerful and more
      easily obtained tools are available for predicting survival. 

PMID- 27049652
TI  - Toward a Minimal Artificial Axon.
AB  - The electrophysiology of action potentials is usually studied in neurons, through
      relatively demanding experiments which are difficult to scale up to a defined
      network. Here we pursue instead the minimal artificial system based on the
      essential biological components-ion channels and lipid bilayers-where action
      potentials can be generated, propagated, and eventually networked. The
      fundamental unit is the classic supported bilayer: a planar bilayer patch with
      embedded ion channels in a fluidic environment where an ionic gradient is imposed
      across the bilayer. Two such units electrically connected form the basic building
      block for a network. The system is minimal in that we demonstrate that one kind
      of ion channel and correspondingly a gradient of only one ionic species is
      sufficient to generate an excitable system which shows amplification and
      threshold behavior.

PMID- 27049653
TI  - Defending against smallpox: a focus on vaccines.
AB  - Smallpox has shaped human history, from the earliest human civilizations well
      into the 20th century. With high mortality rates, rapid transmission, and serious
      long-term effects on survivors, smallpox was a much-feared disease. The
      eradication of smallpox represents an unprecedented medical victory for the
      lasting benefit of human health and prosperity. Concerns remain, however, about
      the development and use of the smallpox virus as a biological weapon, which
      necessitates the need for continued vaccine development. Smallpox vaccine
      development is thus a much-reviewed topic of high interest. This review focuses
      on the current state of smallpox vaccines and their context in biodefense
      efforts.

PMID- 27049654
TI  - Increased Soluble CD155 in the Serum of Cancer Patients.
AB  - Emerging evidence suggests that DNAM-1 (CD226) play an important role in the
      recognition of tumor cells and their lysis by cytotoxic T lymphocytes (CTL) and
      NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various
      tissues, many human tumors significantly upregulate the expression of CD155; DNAM
      1 on CTL and NK cells may be involved in tumor immunity. However, unlike those in
      mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the
      transmembrane region. Here, we show that sCD155 levels were significantly higher
      in the sera of 262 patients with lung, gastrointestinal, breast, and gynecologic
      cancers than in sera from healthy donors. In addition, the sCD155 levels were
      significantly higher in patients with early stage (stages 1 and 2) gastric cancer
      than in healthy donors, and were significantly higher in patients with advanced
      stage (stages 3 and 4) disease than in patients in those with early stage disease
      and healthy donors. Moreover, the sCD155 levels were significantly decreased
      after surgical resection of cancers. Thus, sCD155 level in serum may be
      potentially useful as a biomarker for cancer development and progression. 

PMID- 27049655
TI  - Direction Dependence of Resistive-Pulse Amplitude in Conically Shaped Mesopores.
AB  - Conically shaped pores such as glass pipets as well as asymmetric pores in
      polymers became an important analytics tool used for the detection of molecules,
      viruses, and particles. Electrokinetic or pressure driven passage of single
      particles through a single pore causes a transient change of the transmembrane
      current, called a resistive-pulse, whose amplitude is the measure of the particle
      volume. The shape of the pulse reflects the pore topography, and in a conical
      pore, resistive pulses have a shape of a tick point. Passage of particles in both
      directions was reported to produce pulses of the same amplitude and shapes that
      are mirror images of each other. In this manuscript we identify conditions at
      which the amplitude of resistive-pulses in a conical mesopore is direction
      dependent. Neutral particles entering the pore from the larger entrance of a
      conical pore, called the base, block the current to a larger extent than the
      particles traveling in the opposite direction. Negatively charged particles on
      the other hand size larger when being transported in the direction from tip to
      base. The findings are explained via voltage-regulated ionic concentrations in
      the pore such that for one voltage polarity a weak depletion zone is formed,
      which increases the current blockage caused by a particle. For the opposite
      polarity, an enhancement of ionic concentrations was predicted. The findings
      reported here are of crucial importance for the resistive-pulse technique, which
      relates the current blockage with the size of the passing object.

PMID- 27049656
TI  - Myricitrin and bioactive extract of Albizia amara leaves: DNA protection and
      modulation of fertility and antioxidant-related genes expression.
AB  - CONTEXT: Albizia species are reported to exhibit many biological activities
      including antiovulatory properties in female rats and antispermatogenic and
      antiandrogenic activities in male rats. OBJECTIVE: The present study investigates
      the flavonoids of Albizia amara (Roxb.) B. Boivin (Fabaceae) leaves and evaluates
      their activity on gene expression of fertility and antioxidant glutathione-S
      transferase-related genes of treated female mice in addition to their effect on
      DNA damage. MATERIALS AND METHODS: Plant materials were extracted by using 70%
      methanol for 48 h, the extract was chromatographed on a polyamide 6S column, each
      isolated compound was purified by using Sephadex LH-20 column; its structure was
      elucidated by chemical and spectral methods. Both the leaves extract and
      myricitrin (200, 30 mg/kg bw/d, respectively) were assayed for their effect on
      DNA damage in female mice after four weeks treatment using Comet assay. Their
      modulatory activity on gene expression of fertility (aromatase CYP19 and
      luteinizing hormone LH) and antioxidant glutathione-S-transferase (GST)-related
      genes of treated female mice were investigated by real-time PCR (qPCR). RESULTS:
      Quercetin-3-O-gentiobioside, myricitrin, quercetin-3-O-alpha-rhamnopyranoside,
      myricetin, quercetin and kaempferol were isolated and identified from the studied
      taxa. Myricitrin and the extract induced low rate of DNA damage (4.8% and 5%,
      respectively), compared with the untreated control (4.2%) and significantly down
      regulated the expression of CYP19 and LH genes and up-regulated GST gene.
      DISCUSSION AND CONCLUSION: Our results highlight the potential effect of the
      leaves extract of Albizia amara and myricitrin as fertility-regulating
      phytoconstituents with ability to protect DNA from damage and cells from
      oxidative stress.

PMID- 27049657
TI  - Learning Pitch with STDP: A Computational Model of Place and Temporal Pitch
      Perception Using Spiking Neural Networks.
AB  - Pitch perception is important for understanding speech prosody, music perception,
      recognizing tones in tonal languages, and perceiving speech in noisy
      environments. The two principal pitch perception theories consider the place of
      maximum neural excitation along the auditory nerve and the temporal pattern of
      the auditory neurons' action potentials (spikes) as pitch cues. This paper
      describes a biophysical mechanism by which fine-structure temporal information
      can be extracted from the spikes generated at the auditory periphery. Deriving
      meaningful pitch-related information from spike times requires neural structures
      specialized in capturing synchronous or correlated activity from amongst neural
      events. The emergence of such pitch-processing neural mechanisms is described
      through a computational model of auditory processing. Simulation results show
      that a correlation-based, unsupervised, spike-based form of Hebbian learning can
      explain the development of neural structures required for recognizing the pitch
      of simple and complex tones, with or without the fundamental frequency. The
      temporal code is robust to variations in the spectral shape of the signal and
      thus can explain the phenomenon of pitch constancy. 

PMID- 27049658
TI  - Colchicine-Induced Rhabdomyolysis: An Autopsy Case.
AB  - Colchicine is derived from Colchicum autumnale and Gloriosa superba and is used
      to treat acute gout and familial Mediterranean fever (FMF). Musculoskeletal
      adverse effects range from myopathy to rhabdomyolysis. An 18-year-old woman, with
      a 2-year history of FMF treated with colchicine, took 9 colchicine pills (4.5 mg)
      to relieve severe abdominal pain. On the sixth day of hospitalization, the
      patient's condition worsened, and she died. As this was a case of fatal
      poisoning, a forensic autopsy was performed, and the cause of death was
      determined to be complications of muscle destruction due to colchicine
      intoxication with the findings of myocytolysis, positive antimyoglobin antibody
      staining kidney tubules. Colchicine toxicity begins with gastrointestinal
      symptoms. Multiorgan effects follow the gastrointestinal effects. Serious
      outcomes of colchicine toxicity are rhabdomyolysis, bone marrow suppression, and
      disseminated intravascular coagulation. In chronic diseases that require lifelong
      treatment with medications, adverse effects can arise with long periods of use.
      Our patient had been treated for FMF with colchicine for 2 years but took too
      many colchicine pills to relieve her severe abdominal pain. Warning patients
      about the effects of high doses of drugs and providing information about their
      toxic effects and what to do "in case" of overuse could be lifesaving. 

PMID- 27049659
TI  - Sudden Death Due to Cerebral Leukemic Hemorrhage in a 32-Year-Old Woman Who Had a
      Short-Term Benzene Exposure History.
AB  - Acute myeloid leukemia (AML), also known as acute myelogenous leukemia, is
      associated with severe hemorrhagic coagulopathy, which is induced by the drop in
      red blood cells, platelets, and normal leukocyte and the increase of leukemic
      cells. The case described in this report was of a 32-year-old woman who
      unexpectedly and suddenly died because of cerebral hemorrhage caused by
      undiagnosed AML while hospitalized. Further investigation found that the decedent
      had been exposed to benzene and its derivatives 6 months before her death. This
      case suggests that underlying AML should be considered as a possible diagnosis
      when sudden death occurs with a fatal spontaneous intracerebral hemorrhage,
      especially if the deceased had occupational chemical exposure to benzene and its
      derivatives. 

PMID- 27049660
TI  - Infantile Respiratory Distress Syndrome and Its Probable Links With Parameters of
      the Maternal Patient History: A Forensic Case Report.
AB  - Respiratory distress syndrome (RDS) has a major contribution to neonatal
      mortality worldwide. Multiple factors associated with increased risk for RDS have
      been documented to effectively understand the emergence and progression of this
      disorder. A portion of these parameters has been broadly examined whereas the
      role of others, despite being clinically described, has not been fully evaluated.
      In this report, we analyze a forensic RDS case of a late preterm infant. Taking
      the maternal medical history into account, we focused on 2 not widely established
      risk factors, oligohydramnios and maternal age, discussing their possible
      pathophysiological relation to the development of RDS. Simultaneously, the
      fundamental role of the histopathological examination as a diagnostic tool
      resurfaces. Following a multidisciplinary approach derived from the collaboration
      of clinicians and researchers, the identification of factors that precipitate or
      contribute to this syndrome can be enhanced, leading to novel prognostic and
      therapeutic strategies against RDS. 

PMID- 27049661
TI  - Applying the Principles of Homicide by Heart Attack.
AB  - Homicide by heart attack is a well-established model in forensic pathology that
      describes death elicited during or immediately after a criminal act where a
      threat or fear of physical injury is present. After its introduction nearly 4
      decades ago, the principle has undergone a handful of modifications but still
      maintains its core concepts. All cases of this nature during a 20-year period at
      the Wayne County Medical Examiner's Office were compared and contrasted for
      demographics, circumstances and scene investigation, and autopsy and toxicology
      findings. Of the cases fulfilling the previously established criteria for
      homicide by heart attack, more than 80% displayed significant changes because of
      hypertension. This finding coincides with the high prevalence of hypertension in
      our urban population and highlights the significance of this disease. Also
      present were minor external and internal injuries in select cases, which
      reinforce the understanding that physical contact between the decedent and
      assailant does not preclude this diagnosis. 

PMID- 27049662
TI  - Hyperdensity of the Basilar Artery on Postmortem CT: A Potential Indicator for
      Basilar Artery Thrombosis.
AB  - Basilar artery thrombosis constitutes 1% of all types of stroke, carries a
      mortality rate of up to 90%, and is one of the rarer causes of sudden death. It
      leads to brain stem ischemia and commonly presents with impaired consciousness,
      cranial nerve palsy, hemiplegia or quadriplegia, and sudden collapse. Clinically,
      the diagnosis of basilar artery thrombosis is made on clinical symptoms, along
      with a hyperdense basilar artery in antemortem computed tomography (CT) scan. To
      our knowledge, whether a hyperdense basilar artery indicates basilar artery
      thrombosis on postmortem CT scan is not documented in the literature. We present
      a case report of a 55-year-old man who on postmortem CT scan showed a hyperdense
      basilar artery and was subsequently confirmed to be a fatal basilar artery
      thrombosis. We suggest that a hyperdense basilar artery on postmortem CT should
      prompt the pathologist to consider basilar artery thrombosis. 

PMID- 27049663
TI  - The Prognostic Utility of a Simplified Biventricular Echocardiographic Index of
      Cardiac Remodeling in Patients with Pulmonary Hypertension.
AB  - BACKGROUND: Right ventricular (RV) remodeling has been associated with outcomes
      in patients with pulmonary hypertension (PH). However, the additive prognostic
      significance of RV remodeling and left ventricular (LV) morphology in PH is
      unclear. The objective of this study was to test the hypothesis that the ratio of
      RV end-diastolic area to LV end-diastolic area is a biventricular index
      predictive of outcome in patients with PH. METHODS: In total, 139 patients with
      precapillary PH (mean age, 55 +/- 15 years; 75% women) and 22 control subjects
      (mean age, 40 +/- 17 years; 73% women) were studied. The apical four-chamber view
      was used to measure the RV-to-LV end-diastolic area ratio as an index of
      biventricular cardiac remodeling. RV free wall and global strain were measured
      using speckle-tracking echocardiography. The study design was prospective, with
      all-cause mortality over 5 years predefined as the outcome event. RESULTS:
      Patients with PH had significantly larger RV to LV end-diastolic area ratios than
      normal subjects, as expected (1.06 vs 0.67, P < .0001). There were 72 deaths over
      5 years. Using a cutoff value of 0.93, patients with RV-to-LV ratios >= 0.93 had
      significantly higher all-cause mortality (hazard ratio,1.84; 95% CI, 1.14-2.96; P
      = .019). RV global strain was also significantly associated with survival using a
      cutoff of >=-15% (hazard ratio, 1.66; 95% CI, 1.03-2.67; P = .044). In a
      multivariate analysis, only age and biventricular index were independent
      predictors of survival among other clinical and echocardiographic features.
      CONCLUSIONS: The RV-to-LV end-diastolic area ratio is a simplified biventricular
      echocardiographic index of cardiac remodeling that is predictive of long-term
      survival in patients with PH.

PMID- 27049664
TI  - Safety and Efficacy of Cardiac Ultrasound Contrast in Children and Adolescents
      for Resting and Stress Echocardiography.
AB  - BACKGROUND: Small pilot studies of ultrasound contrast (UC) echocardiography in
      children have suggested that it is safe; therefore, larger scale evaluation of
      safety and efficacy in this population is of particular interest. METHODS: This
      was a retrospective study (January 2005 to June 2014). Known intracardiac shunt
      was the only exclusion criterion. UC echocardiography was performed on
      commercially available ultrasound systems using Definity (3% infusion). When
      indicated, real-time myocardial contrast echocardiography was performed at rest
      and stress, with examination of myocardial contrast replenishment, plateau
      intensity, and wall motion. The primary outcome was short-term safety and
      efficacy (<24 hours). RESULTS: In all, 113 patients (55% male; mean age, 17.8 +/-
      3 years; age range, 5-21 years) underwent UC echocardiography for left
      ventricular opacification or stress wall motion and perfusion analysis. Diagnosis
      categories were congenital heart disease (30%), acquired heart disease (21%), and
      other (suspected cardiac complications of disease of other organ systems; 49%).
      Twelve patients (11%) with right ventricular systolic pressures > 40 mm Hg
      received UC without complications; four of these (33%) had the highest right
      ventricular-right atrial gradient recorded with ultrasound contrast-enhanced
      Doppler. Myocardial perfusion and/or UC echocardiography-detected wall motion
      abnormalities were seen in 13 patients (12%); four had confirmed correlations by
      angiography or magnetic resonance imaging. There were 13 instances of adverse
      events or reported symptoms during UC echocardiography. All symptoms and events
      were transient, all patients completed protocols, and there were no immediate
      sequelae. CONCLUSIONS: These data demonstrate the usefulness and safety of UC
      echocardiography in children and adolescents for a wide variety of indications.
      UC echocardiography provided myocardial perfusion and wall motion information
      important in clinical decision making.

PMID- 27049665
TI  - Fetal and Neonatal Diastolic Myocardial Strain Rate: Normal Reference Ranges and
      Reproducibility in a Prospective, Longitudinal Cohort of Pregnancies.
AB  - BACKGROUND: Normative fetal diastolic strain rate values have not been
      comprehensively reported. The aims of this study were to report normative data
      for diastolic strain rate parameters across gestation and upon delivery,
      determine the effect of advancing gestational age on these measures, and compare
      interobserver variability at multiple gestational age time points. METHODS: Sixty
      gravid women were enrolled before 20 weeks' gestation. The following measures
      were obtained by two blinded observers at five time points across gestation and
      at 4 to 8 weeks' postnatal age: global left ventricular circumferential strain
      rate peak E and A waves, global left and right ventricular longitudinal strain
      rate peak E and A waves, and mitral and tricuspid valve E/A ratios.
      Reproducibility was assessed using intraclass correlation and Bland-Altman
      analysis. Least square means analysis was used to evaluate for changes across
      gestational age. RESULTS: Left ventricular longitudinal and circumferential
      diastolic strain rate values decreased across gestation, while right ventricular
      longitudinal values remained stable. With delivery, left ventricular values
      remained fairly stable, while right ventricular values increased. Intraclass
      correlations for diastolic strain rate values were 0.68 to 0.94 at >=24 weeks'
      gestation and 0.25 to 0.82 for values at 20 to 21 weeks' gestation. Intraclass
      correlations ranged from 0.49 to 0.90 for mitral valve and tricuspid valve E/A
      ratios across gestation. CONCLUSIONS: Fetal measures of diastolic strain rate
      have acceptable reproducibility after 24 weeks' gestation. The described changes
      across gestation likely reflect intrinsic myocardial adaptation to loading
      conditions. These reference ranges can be used to assess effects of various
      disease states on fetal myocardial deformation.

PMID- 27049666
TI  - Successful neuropsychological rehabilitation in a patient with Cerebellar
      Cognitive Affective Syndrome.
AB  - The objective of this case study was to describe the neuropsychological
      rehabilitation of a 16-year-old patient who presented a Cerebellar Cognitive
      Affective Syndrome (CCAS) following a bilateral cerebellar hemorrhage. The
      patient presented severe and diffuse cognitive deficits, massive behavioral
      disorders, and emotion regulation difficulties. The cognitive rehabilitation was
      performed in the chronic phase (one year after the onset of the hemorrhage) using
      a transdisciplinary neurobehavioral approach based on the patient's favorite
      interest (soccer). A significant behavioral and cognitive improvement was
      observed. The patient became progressively independent in all activities of daily
      living and was discharged home. The Functional Independence Measure at discharge
      was 124/126 (vs. 37/126 at entry). The patient was able to complete his schooling
      despite the mild cognitive and behavioral sequelae. This first description of the
      use of neurobehavioral therapy in a case of chronic CCAS suggests that (a) major
      clinical improvement can occur more than one year after the onset of the CCAS,
      showing the importance of long-term and intensive neurorehabilitation; and (b)
      when the cerebellum cannot properly play its regulator role in cognition,
      neuropsychological intervention through a behavioral and cognitive approach can
      be of great help by acting as an external modulator to help the patient regain
      control over himself.

PMID- 27049667
TI  - Chronic Hyperinsulinemia Increases Myoblast Proliferation in Fetal Sheep Skeletal
      Muscle.
AB  - Insulin is an important fetal growth factor. However, chronic experimental
      hyperinsulinemia in the fetus fails to accelerate linear and lean mass growth
      beyond normal rates. Mechanisms preventing accelerated lean mass accretion during
      hyperinsulinemia are unknown. To address potential mechanisms, late-gestation
      fetal sheep were infused with iv insulin and glucose to produce euglycemic
      hyperinsulinemia (INS) or saline for 7-9 days. Fetal substrate uptake and protein
      metabolic rates were measured. INS fetuses had 1.5-fold higher insulin
      concentrations (P < .0001) and equivalent glucose concentrations. INS fetuses had
      20% more Pax7(+) nuclei in the biceps femoris, which indicates the potential for
      hyperinsulinemia to increase the number of myoblasts within late-gestation fetal
      skeletal muscle. Additionally, the percentage of Pax7(+) myoblasts that expressed
      Ki-67 was 1.3-fold higher and expression of myogenic regulatory factors was 50%
      lower in INS fetuses (MYF5 and MYOG [myogenin], P < .005), which indicates a
      shift toward myoblast proliferation over differentiation. There were no
      differences for fetal body, organ, or muscle weights, although INS placentas
      weighed 28% less (P < .05). Protein synthesis and accretion rates did not change
      in INS fetuses, nor did fiber muscle size. Essential amino acid concentrations
      were lower in the INS group (P < .05) except for tryptophan. Umbilical blood
      flow, net total amino acids, and O2 uptakes rates did not differ between groups.
      Arterial O2 content was 33% lower (P < .005) and norepinephrine was 100% higher
      in the INS fetuses (P < .01), all of which are factors that may counteract fetal
      protein accretion during hyperinsulinemia despite an increase in myoblast
      proliferation.

PMID- 27049668
TI  - Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in
      Proliferating Fibroblasts.
AB  - Cellular proliferation requires the formation of new membranes. It is often
      assumed that the lipids needed for these membranes are synthesized mostly de
      novo. Here, we show that proliferating fibroblasts prefer to take up palmitate
      from the extracellular environment over synthesizing it de novo. Relative to
      quiescent fibroblasts, proliferating fibroblasts increase their uptake of
      palmitate, decrease fatty acid degradation, and instead direct more palmitate to
      membrane lipids. When exogenous palmitate is provided in the culture media at
      physiological concentrations, de novo synthesis accounts for only a minor
      fraction of intracellular palmitate in proliferating fibroblasts as well as
      proliferating HeLa and H460 cells. Blocking fatty acid uptake decreased the
      proliferation rate of fibroblasts, HeLa, and H460 cells, while supplementing
      media with exogenous palmitate resulted in decreased glucose uptake and rendered
      cells less sensitive to glycolytic inhibition. Our results suggest that cells
      scavenging exogenous lipids may be less susceptible to drugs targeting glycolysis
      and de novo lipid synthesis.

PMID- 27049669
TI  - Small-Molecule Target Engagement in Cells.
AB  - Monitoring how, when, and where small molecules engage their targets inside
      living cells is a critical step in chemical biology and pharmacological research,
      because it enables compound efficacy and confirmation of mode of action to be
      assessed. In this mini-review we summarize the currently available methodologies
      to detect and prove direct target engagement in cells and offer a critical view
      of their key advantages and disadvantages. As the interest of the field shifts
      toward discovery and validation of high-quality agents, we expect that efforts to
      develop and refine these types of methodologies will also intensify in the near
      future.

PMID- 27049670
TI  - Epiblastin A Induces Reprogramming of Epiblast Stem Cells Into Embryonic Stem
      Cells by Inhibition of Casein Kinase 1.
AB  - The discovery of novel small molecules that induce stem cell reprogramming and
      give efficient access to pluripotent stem cells is of major importance for
      potential therapeutic applications and may reveal novel insights into the factors
      controlling pluripotency. Chemical reprogramming of mouse epiblast stem cells
      (EpiSCs) into cells corresponding to embryonic stem cells (cESCs) is an
      inefficient process. In order to identify small molecules that promote this
      cellular transition, we analyzed the LOPAC library in a phenotypic screen
      monitoring Oct4-GFP expression and identified triamterene (TR) as initial hit.
      Synthesis of a TR-derived compound collection and investigation for reprogramming
      of EpiSCs into cESCs identified casein kinases 1 (CK1) alpha/delta/E as
      responsible cellular targets of TR and unraveled the structural parameters that
      determine reprogramming. Delineation of a structure-activity relationship led to
      the development of Epiblastin A, which engages CK1 isoenzymes in cell lysate and
      induces efficient conversion of EpiSCs into cESCs.

PMID- 27049671
TI  - Retraction notice to "The identification of loci for polydactyly in chickens
      using a genome-wide association study" [GENE 568/2 (2015) 176-180].

PMID- 27049672
TI  - Editorial.

PMID- 27049673
TI  - Comprehensive analysis of the clinical and urodynamic outcomes of primary
      tethered spinal cord before and after spinal cord untethering.
AB  - INTRODUCTION: Primary tethered spinal cord (TSC) refers to a group of
      abnormalities associated with a posterior bony spinal defect that develops
      beneath an intact dermis and epidermis. There is relative agreement that patients
      with symptomatic TSC will require surgical intervention. However, it is still
      debatable as to how to approach asymptomatic patients with primary TSC.
      OBJECTIVE: To study the clinical and urodynamic (UDS) outcomes of patients with
      primary TSC after spinal cord untethering (SCU). STUDY DESIGN: Charts of patients
      with primary TSC between 1998 and 2010 were retrospectively reviewed. Patients
      that underwent before and after SCU clinical and UDS evaluation with minimum of 5
      years follow-up were included. Continence status was assessed in children >=5
      years. Patients with dry intervals of >=4 h were considered continent. Urologic
      and neuro-orthopedic manifestations, as well as UDS parameters, were compared
      before and after SCU. Categorical data were compared using Fisher-Exact test and
      continuous variables were compared using Wilcoxon-Signed-Rank test. A P-value
      <0.05 was considered significant. RESULTS: Twenty-two patients met the inclusion
      criteria. The median age at time of SCU was 11.5 months (range 3-211). The median
      age at time of follow-up UDS after SCU was 22 months (range 9-218). The median
      age at time of last follow-up was 153.5 months (range 65-228). The median follow
      up time was 71 months (range 60-192). A total of 14/22 patients had clinical
      manifestation before SCU, while 8/22 were asymptomatic and diagnosed based on
      magnetic resonance imaging/UDS findings. Of the symptomatic patients, 86% had
      symptom improvement after SCU. The UDS parameters showed statistically
      significant improvement in the median percentage of change of actual bladder
      capacity (P = 0.01), median intravesical pressure for patients with pre-operative
      pressure >=40 cm/H2O at total cystometric bladder capacity (P = 0.012), and
      median bladder compliance at 75% bladder capacity (P = 0.01) (Table). DISCUSSION:
      Tethered spinal cord syndrome (TSCS) is a clinical entity that presents with
      neurological, urological, and/or orthopedic symptoms caused by primary or
      secondary tethering of the spinal cord, which may result in ischemic damage of
      the neural tissue and symptom development. While some authors believe that
      surgical management should be reserved for symptomatic patients, others prefer
      prophylactic surgery to avoid possible irreversible neurological damage. The
      present study provides detailed discussion of the clinical and UDS outcomes for
      patients with primary TSC that underwent SCU. CONCLUSION: For patients with
      primary TSC, spinal cord untethering is beneficial in terms of clinical and UDS
      outcomes. A prospective long-term study with large numbers could further
      highlight outcomes for this particular group of patients.

PMID- 27049674
TI  - Advances in the diagnosis, management, and treatment of neonates with laryngeal
      disorders.
AB  - Neonatal airway obstruction due to laryngeal pathology may cause significant
      morbidity and even mortality. The most frequently occurring etiologies
      anatomically from superiorly to inferiorly include: laryngomalacia, saccular
      cyst, vocal fold paralysis, anterior glottic web, laryngeal atresia, laryngeal
      cleft, subglottic stenosis, and subglottic hemangioma. The pathophysiology,
      presentation, and treatment options for each of these entities are discussed with
      a focus on a multidisciplinary, evidence-based approach. 

PMID- 27049675
TI  - Microcephaly and Zika virus: a clinical and epidemiological analysis of the
      current outbreak in Brazil.
AB  - OBJECTIVE: This study aimed to critically review the literature available
      regarding the Zika virus outbreak in Brazil and its possible association with
      microcephaly cases. SOURCES: Experts from Instituto do Cerebro do Rio Grande do
      Sul performed a critical (nonsystematic) literature review regarding different
      aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology,
      diagnostic criteria, and its possible association with the increase of
      microcephaly reports. The PubMed search using the key word "Zika virus" in
      February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all
      publications/guidelines from the Brazilian Ministry of Health, World Health
      Organization and Centers for Disease Control and Prevention (CDC - United
      States). SUMMARY OF FINDINGS: Epidemiological data suggest a temporal association
      between the increased number of microcephaly notifications in Brazil and outbreak
      of Zika virus, primarily in the Brazil's Northeast. It has been previously
      documented that many different viruses might cause congenital acquired
      microcephaly. Still there is no consensus on the best curve to measure cephalic
      circumference, specifically in preterm neonates. Conflicting opinions regarding
      the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be
      used for the notifications were also found in the literature. CONCLUSION: The
      development of diagnostic techniques that confirm a cause-effect association and
      studies regarding the physiopathology of the central nervous system impairment
      should be prioritized. It is also necessary to strictly define the criteria for
      the diagnosis of microcephaly to identify cases that should undergo an
      etiological investigation.

PMID- 27049676
TI  - Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the
      female rat brain during postnatal development.
AB  - Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ecto
      enzyme which hydrolyzes extracellular ATP, thus modulating the function of
      purinergic receptors and the pattern of purinergic signaling. Here we analyzed
      the developmental expression of NTPDase3 in female hypothalamus, cerebral cortex
      and hippocampal formation at different postnatal ages (PD7-PD90) by qRT-PCR and
      immunohistochemistry. In hypothalamus and hippocampus, a similar developmental
      profile was seen: NTPDase3 gene expression was stable during postnatal
      development and increased in adults. In the cortex, upregulation of NTPDase3 mRNA
      expression was seen at PD15 and further increase was evidenced in adults.
      Immunohistochemical analysis at PD7 revealed faint neuronal NTPDase3 localization
      in a dorsal hypothalamus. The immunoreactivity (ir) gradually increased in PD15
      and PD20, in clusters of cells in the lateral, ventral and dorsomedial
      hypothalamus. Furthermore, in PD20 animals, NTPDase3-ir was detected on short
      fibers in the posterior hypothalamic area, while in PD30 the fibers appeared
      progressively longer and markedly varicose. In adults, the strongest NTPDase3-ir
      was observed in collections of cells in dorsomedial hypothalamic nucleus, dorsal
      and lateral hypothalamus and in several thalamic areas, whereas the varicose
      fibers traversed entire diencephalon, particularly paraventricular thalamic
      nucleus, ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus
      and the prefornical part of the lateral hypothalamus. The presumably ascending
      NTPDase3-ir fibers were first observed in PD20; their density and the varicose
      appearance increased until the adulthood. Prominent enhancement of NTPDase3-ir in
      the hypothalamus coincides with age when animals acquire diurnal rhythms of
      sleeping and feeding, supporting the hypothesis that this enzyme may be involved
      in regulation of homeostatic functions.

PMID- 27049677
TI  - Biological applications of hydrophilic C60 derivatives (hC60s)- a structural
      perspective.
AB  - Reactive oxygen species (ROS) generation and radical scavenging are dual
      properties of hydrophilic C60 derivatives (hC60s). hC60s eliminate radicals in
      dark, while they produce reactive oxygen species (ROS) in the presence of
      irradiation and oxygen. Compared to the pristine C60 suspension, the aqueous
      solution of hC60s is easier to handle in vivo. hC60s are diverse and could be
      placed into two general categories: covalently modified C60 derivatives and
      pristine C60 solubilized non-covalently by macromolecules. In order to present in
      detail, the above categories are broken down into 8 parts: C60(OH)n, C60 with
      carboxylic acid, C60 with quaternary ammonium salts, C60 with peptide, C60
      containing sugar, C60 modified covalently or non-covalently solubilized by
      cyclodextrins (CDs), pristine C60 delivered by liposomes, functionalized C60
      polymer and pristine C60 solubilized by polymer. Each hC60 shows the propensity
      to be ROS producer or radical scavenger. This preference is dependent on hC60s
      structures. For example, major application of C60(OH)n is radical scavenger,
      while pristine C60/gamma-CD complex usually serves as ROS producer. In addition,
      the electron acceptability and innate hydrophobic surface confer hC60s with O2
      uptake inhibition, HIV inhibition and membrane permeability. In this review, we
      summarize the preparation methods and biological applications of hC60s according
      to the structures. 

PMID- 27049678
TI  - VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene
      based inhibitors of rhinovirus 14 infection.
AB  - Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like
      illnesses, but are also responsible for virus-induced exacerbations of asthma and
      chronic obstructive pulmonary disease. However, to date, no drug has been
      approved yet for clinical use. In this study, we present the results of the
      structure-based lead optimization of a class of new small-molecule inhibitors
      that we previously reported to bind into the pocket beneath the canyon of the VP1
      protein. A small series of analogues that we designed based on the available
      structure and interaction data were synthesized and evaluated for their potency
      to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyl)-1
      (4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor
      exhibiting micromolar activity (EC50 = 3.4 +/- 1.0 MUM) with a toxicity for HeLa
      cells that was significantly lower than that of our previous hit (LPCRW_0005,
      CC50 = 104.0 +/- 22.2 MUM; 3v, CC50 > 263 MUM). 

PMID- 27049679
TI  - Surgical Case Logging Habits and Attitudes: A Multispecialty Survey of Residents.
AB  - OBJECTIVE: The Accreditation Council for Graduate Medical Education measures
      surgical residents' experience in the United States by mandating that residents
      log each procedure in which they have participated. This system is the primary
      mechanism by which breadth and depth of surgical training are documented, and
      data are used for program accreditation and by individual program directors to
      assess resident preparedness. The study objective was to learn from residents
      across surgical specialties how this system is being used, and whether they
      believe these data are reliable. DESIGN: Investigators developed and administered
      a voluntary, 45-item survey. Resident demographic data, program details, logging
      behaviors, and attitudes were examined using descriptive statistics. Authors used
      multivariate logistic regression to assess respondent and program characteristics
      associated with logging habits. SETTING: The survey was administered at a large
      academic medical center. PARTICIPANTS: All general surgery, obstetrics and
      gynecology, orthopedics, urology, neurosurgery, otolaryngology, and plastic
      surgery residents were eligible. Of 126 surgical residents, 82 participated,
      yielding a response rate of 65%. RESULTS: Overall, 7.5% considered the case log
      system highly inaccurate, 28.8% somewhat inaccurate, 52.5% somewhat accurate, and
      11.3% highly accurate. Nearly half (48.1%) use an incorrect metric to log their
      role as surgeon or assistant. Half logged monthly or less frequently. The longest
      time residents reported falling behind ranged from less than a week to more than
      a year, with about half (51.4%) reporting backlogs of 3 months or longer.
      Approximately two-thirds considered the system difficult to navigate (64.2%) and
      burdensome (68.8%). Departmental training and reminders to log were associated
      with high fidelity logging habits. CONCLUSIONS: Inconsistency of logging habits
      and perceived lack of accuracy raise concerns about use of the system for
      assessing surgical preparedness or accrediting training programs. Academic
      departments playing an active role may benefit from more reliable data to guide
      improvements in surgical training.

PMID- 27049680
TI  - Association of Youth and Caregiver Anxiety and Asthma Care Among Urban Young
      Adolescents.
AB  - OBJECTIVE: To examine the association of adolescent asthma-related anxiety,
      social anxiety, separation anxiety, and caregiver asthma-related anxiety with
      asthma care by urban adolescents. METHODS: Participants were 386 ethnic minority
      adolescents (mean age 12.8 years) with persistent asthma and their caregivers.
      Adolescents reported what they do to prevent asthma symptoms and to manage acute
      symptoms, and if they or their caregiver is responsible for their asthma care.
      Adolescents completed the Youth Asthma-Related Anxiety Scale, and the social and
      separation anxiety subscales of the Screen for Child Anxiety and Emotional
      Disorders (SCARED); caregivers completed the Parent Asthma-Related Anxiety Scale.
      Linearity of the associations was assessed by generalized additive models. When
      there was no evidence for nonlinearity, linear mixed effects models were used to
      evaluate the effects of the predictors. RESULTS: Adolescent asthma-related
      anxiety had a strong curvilinear relationship with symptom prevention (P < .001).
      Adolescents took more prevention steps as their anxiety increased, with a plateau
      at moderate anxiety. There was a linear relationship of adolescent asthma-related
      anxiety to symptom management (beta = 0.03, P = .021) and to asthma
      responsibility (beta = 0.11, P = .015), and of caregiver asthma-related anxiety
      to adolescent symptom prevention (beta = 0.04, P = .001). Adolescent social and
      separation anxiety had weak to no relationship with asthma care. Results remained
      consistent when controlling for each of the other anxieties. CONCLUSIONS: Asthma
      related anxiety plays an important, independent role in asthma care. When low,
      adolescents may benefit from increased support from caregivers and awareness of
      the consequences of uncontrolled asthma. When elevated, health providers should
      ensure the adolescents are not assuming responsibility for asthma care
      prematurely.

PMID- 27049681
TI  - Long Noncoding RNA PICSAR Promotes Growth of Cutaneous Squamous Cell Carcinoma by
      Regulating ERK1/2 Activity.
AB  - Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common
      metastatic skin cancer, and its incidence is increasing globally. Long noncoding
      RNAs (lncRNA) are involved in various biological processes, and their role in
      cancer progression is emerging. Whole transcriptome analysis of cSCC cells (n =
      8) and normal human epidermal keratinocytes (n = 4) revealed overexpression of
      long intergenic ncRNA (LINC00162) in cSCC cells. The expression of LINC00162 in
      cSCC cells was upregulated by inhibition of the p38alpha and p38delta mitogen
      activated protein kinases. Analysis of tissue sections by RNA in situ
      hybridization showed that LINC00162 is specifically expressed by tumor cells in
      cSCCs but not by keratinocytes in normal skin in vivo. Knockdown of LINC00162
      inhibited proliferation and migration of cSCC cells, and suppressed the growth of
      human cSCC xenografts in vivo. Furthermore, knockdown of LINC00162 inhibited
      extracellular signal-regulated kinase 1/2 activity and upregulated expression of
      dual specificity phosphatase 6 (DUSP6) in cSCC cells. Based on these
      observations, LINC00162 was named p38 inhibited cutaneous squamous cell carcinoma
      associated lincRNA (PICSAR). Our results provide mechanistic evidence for the
      role of PICSAR in promoting cSCC progression via activation of extracellular
      signal-regulated kinase 1/2 signaling pathway by downregulating DUSP6 expression.
      These results also identify PICSAR as a biomarker and putative therapeutic target
      in cSCC.

PMID- 27049682
TI  - Natural History, Diagnostic Approaches, and Therapeutic Strategies for Patients
      With Asymptomatic Severe Aortic Stenosis.
AB  - Aortic stenosis (AS) is one of the most common valvular diseases encountered in
      clinical practice. Current guidelines recommend aortic valve replacement (AVR)
      when the aortic valve is severely stenotic and the patient is symptomatic;
      however, a substantial proportion of patients with severe AS are asymptomatic at
      the time of first diagnosis. Although specific morphological valve features,
      exercise testing, stress imaging, and biomarkers can help to identify patients
      with asymptomatic severe AS who may benefit from early AVR, the optimal
      management of these patients remains uncertain and controversial. The current
      report presents a comprehensive review of the natural history and the diagnostic
      evaluation of asymptomatic patients with severe AS, and is followed by a meta
      analysis from reported studies comparing an early AVR strategy to active
      surveillance, with an emphasis on the level of evidence substantiating the
      current guideline recommendations. Finally, perspectives on directions for future
      investigation are discussed.

PMID- 27049683
TI  - Neuropsychological Markers of Suicidal Risk in the Context of Medical
      Rehabilitation.
AB  - While great strides have been made to advance the understanding of the
      neurobiology of suicidal behavior (SB), the neural and neuropsychological
      mechanisms associated with SB are not well understood. The purpose of the current
      study is to identify neurocognitive markers of SB in the context of medical
      rehabilitation. The performances of 39 patients at a medical rehabilitation
      center, aged 21-78, were examined on a series of neurocognitive executive tasks
      decision-making (Iowa Gambling Task - IGT), mental flexibility (WCST), response
      inhibition (SST) and working memory (digit span). Self-report questionnaires were
      administered, for Suicidal behaviors, depression, Anxiety, and PTSD as well as
      perceived social support. Suicidal participants performed more poorly on the IGT.
      A mediation analysis presented a significant direct effect of decision making on
      suicidal risk (p < 0.14) as well as significant indirect effect of decision
      making on suicidal risk that was mediated by the depressive symptoms (95% BCa CI
      [-0.15, -0.018]) with a medium effect size (kappa2 = 0.20, 95% BCa CI [0.067,
      0.381]). Despite the complexity of relationship between decision-making and
      suicidal risk, these results suggest that clinicians should routinely assess
      decision-making abilities in adults at risk for suicide due to the fact that
      impaired decision-making may increase suicidal risk above and beyond that
      conferred by depression.

PMID- 27049684
TI  - Blocking the Transmission of a Noncirculative Vector-Borne Plant Pathogenic
      Bacterium.
AB  - The successful control of insect-borne plant pathogens is often difficult to
      achieve due to the ecologically complex interactions among pathogens, vectors,
      and host plants. Disease management often relies on pesticides and other
      approaches that have limited long-term sustainability. To add a new tool to
      control vector-borne diseases, we attempted to block the transmission of a
      bacterial insect-transmitted pathogen, the bacterium Xylella fastidiosa, by
      disrupting bacteria-insect vector interactions. X. fastidiosa is known to attach
      to and colonize the cuticular surface of the mouthparts of vectors; a set of
      recombinant peptides was generated and the chemical affinities of these peptides
      to chitin and related carbohydrates was assayed in vitro. Two candidates, the X.
      fastidiosa hypothetical protein PD1764 and an N-terminal region of the
      hemagglutinin-like protein B (HxfB) showed affinity for these substrates. These
      proteins were provided to vectors via an artificial diet system in which insects
      acquire X. fastidiosa, followed by an inoculation access period on plants under
      greenhouse conditions. Both PD1764 and HxfAD1-3 significantly blocked
      transmission. Furthermore, bacterial populations within insects over a 10-day
      period demonstrated that these peptides inhibited cell adhesion to vectors but
      not bacterial multiplication, indicating that the mode of action of these
      peptides is restricted to limiting cell adhesion to insects, likely via
      competition for adhesion sites. These results open a new venue in the search for
      sustainable disease-control strategies that are pathogen specific and may have
      limited nontarget effects. 

PMID- 27049685
TI  - Eradicating abusive behavior: Time to adjust the educational paradigm.

PMID- 27049689
TI  - Risk Factors for Retreatment Following Myopic LASIK with Femtosecond Laser and
      Custom Ablation for the Treatment of Myopia.
AB  - PURPOSE: To identify risks factors for retreatment post-laser in situ
      keratomeliusis (LASIK). MATERIALS & METHODS: A retrospective chart review from
      December 2008 to September 2012 identified 1,402 patients (2,581 eyes) that
      underwent LASIK treatment for myopia with the IntralaseTM FS, STAR S4 IRTM
      Excimer Laser, and WaveScan WaveFrontTM technology. In this group, 83 patients
      were retreated. All charts were reviewed for preoperative age, gender, initial
      manifest refraction spherical equivalent (MRSE), total astigmatism, and iris
      registration. RESULTS: Increased incidence rates of retreatment post-LASIK were
      preoperative age >40 years (p < 0.001), initial MRSE > -3.0 D (p = 0.02), and
      astigmatism >1D (p = 0.001). Iris registration capture did not significantly
      reduce the retreatment rate (p = 0.12). CONCLUSIONS: Risk factors for retreatment
      included preoperative age >40 years, initial MRSE > -3.0 D, and astigmatism >1D.
      There was no difference in retreatment rate for patients based on gender or iris
      registration capture.

PMID- 27049690
TI  - Fcgamma1 fragment of IgG1 as a powerful affinity tag in recombinant Fc-fusion
      proteins: immunological, biochemical and therapeutic properties.
AB  - Affinity tags are vital tools for the production of high-throughput recombinant
      proteins. Several affinity tags, such as the hexahistidine tag, maltose-binding
      protein, streptavidin-binding peptide tag, calmodulin-binding peptide, c-Myc tag,
      glutathione S-transferase and FLAG tag, have been introduced for recombinant
      protein production. The fragment crystallizable (Fc) domain of the IgG1 antibody
      is one of the useful affinity tags that can facilitate detection, purification
      and localization of proteins and can improve the immunogenicity, modulatory
      effects, physicochemical and pharmaceutical properties of proteins. Fcgamma
      recombinant forms a group of recombinant proteins called Fc-fusion proteins
      (FFPs). FFPs are widely used in drug discovery, drug delivery, vaccine design and
      experimental research on receptor-ligand interactions. These fusion proteins have
      become successful alternatives to monoclonal antibodies for drug developments. In
      this review, the physicochemical, biochemical, immunological, pharmaceutical and
      therapeutic properties of recombinant FFPs were discussed as a new generation of
      bioengineering strategies.

PMID- 27049691
TI  - A clinimetric analysis of the Hopkins Symptom Checklist (SCL-90-R) in general
      population studies (Denmark, Norway, and Italy).
AB  - BACKGROUND: Although the Symptom Checklist (SCL-90-R) is one of the most widely
      used self-reported scales covering several psychopathological states, the
      scalability of the SCL-90-R has been found to be very problematic. AIMS: We have
      performed a clinimetric analysis of the SCL-90-R, taking both its factor
      structure and scalability (i.e. total scale score a sufficient statistic) into
      account. METHODS: The applicability of the SCL-90-R has been found acceptable in
      general population studies from Denmark, Norway and Italy. These studies were
      examined with principal component analysis (PCA) to identify the factor
      structure. The scalability of the traditional SCL-90-R subscales (i.e.
      somatization, hostility, and interpersonal sensitivity) as well as the affective
      subscales (i.e. depression and anxiety and ADHD), were tested by Mokken's item
      response theory model. RESULTS: Across the three general population studies the
      traditional scaled SCL-90-R factor including 83 items was identified by PCA. The
      Mokken analysis accepted the scalability of both the general factor and the
      clinical SCL-90-R subscales under examination. CONCLUSION: The traditional,
      scaled, general 83 item SCL-90-R scale is a valid measure of general
      psychopathology. The SCL-90-R subscales of somatization, hostility, and
      interpersonal sensitivity as well as the affective subscales of depression,
      anxiety, and ADHD were all accepted by the Mokken test for scalability, i.e.
      their total scores are sufficient statistics.

PMID- 27049692
TI  - Longitudinal Dynamics of Substance Use and Psychiatric Symptoms in Count Data
      with Zero Inflation.
AB  - We examine the dynamics of substance use and psychiatric symptoms from childhood
      to adolescence using a longitudinal study of Mexican-origin families (N = 674).
      We present a longitudinal model capturing the trajectories of substance use and
      psychiatric symptoms (depression, conduct disorder), as well as the
      interrelations between these trajectories over time. Such a model is an extension
      of latent change score models designed to account for the occurrence of
      psychiatric symptoms while also accommodating a large amount of zeros for
      nonoccurrence and characterizing the changes over time in the count data. We
      compare this model with a more traditional approach based on a log transformation
      of the data. We describe differences between these approaches and highlight the
      benefits of using the two-part model when the data include a large amount of
      zeros for nonoccurrence of the behavior. 

PMID- 27049693
TI  - Development, feasibility, and validity of a computer-based utility assessment
      tool for measuring asthma-specific health utilities in Malaysia using the
      standard gamble method.
AB  - OBJECTIVES: To develop and test the feasibility and validity of a computer-based
      utility assessment tool that used standard gamble (SG) method for measuring
      asthma-specific health utilities. METHODS: A computer-based SG (CBSG) tool was
      developed using Microsoft(r) PowerPoint 2007 to value asthma-specific health
      states in Malaysia. Eight hypothetical health states were considered, including
      two anchor states (healthy and dead), three chronic (C) states and three
      temporary (T) states (each numbered 1 through 3, with increasing severity) in
      addition to the subject's current health state. Twenty adult asthma patients
      completed the CBSG tool in addition to paper-based Asthma Control Test, three
      health status measures (EQ-5D, EQ-VAS, and Mini Asthma Quality of Life
      Questionnaire (MiniAQLQ)), and VAS utility assessment tool. Patients and
      interviewers rated the difficulty of the VAS and CBSG tools. Correlations between
      current health state values derived from the various measures were determined.
      RESULTS: The SG and the VAS received similar difficulty ratings. 17 patients
      completed the CBSG tool within 30 minutes. The mean utilities determined by the
      CBSG tool for the T1-T3 asthma health states met the expected logical order of
      1>2>3, but those for the C1-C3 states did not. Correlation between current health
      state values derived from the CBSG tool and other measurement tools was poor.
      CONCLUSION: The CBSG tool developed for measuring utilities of asthma health
      states showed acceptable feasibility and overall validity.

PMID- 27049694
TI  - Gender inequalities in excess adiposity and anaemia combine in a large double
      burden of malnutrition gap detrimental to women in an urban area in North Africa.
AB  - OBJECTIVE: The nutrition transition has exacerbated the gender gap in health in
      the Middle East and North Africa region as the increase in excess adiposity has
      been much higher among women than men. This is not exclusive of the persistence
      of anaemia, generally also more prevalent among women. We assessed the magnitude
      and sociodemographic factors associated with gender inequality vis-a-vis the
      double burden of excess adiposity and anaemia. DESIGN: Cross-sectional study,
      stratified two-stage cluster sample. BMI (=weight/height2) >=25.0 kg/m2 defined
      overweight and BMI>=30.0 kg/m2 obesity. Anaemia was defined as Hb <120 g/l for
      women, <130 g/l for men. Gender inequalities vis-a-vis the within-subject
      coexistence of excess adiposity and anaemia were assessed by women v. men
      relative prevalence ratios (RPR). Their variation with sociodemographic
      characteristics used models including gender * covariate interactions. SETTING:
      Greater Tunis area in 2009-2010. SUBJECTS: Adults aged 20-49 years (women, n
      1689; men, n 930). RESULTS: Gender inequalities in excess adiposity were high
      (e.g. overweight: women 64.9 % v. men 48.4 %; RPR=2.1; 95 % CI 1.6, 2.7) and much
      higher for anaemia (women 38.0 % v. men 7.2 %; RPR=8.2; 95 % CI 5.5, 12.4). They
      were striking for overweight and anaemia (women 24.1 % v. men 3.4 %; RPR=16.2; 95
      % CI 10.3, 25.4). Gender inequalities in overweight adjusted for covariates
      increased with age but decreased with professional activity and household wealth
      score; gender inequality in anaemia or overweight and anaemia was more uniformly
      distributed. CONCLUSIONS: Women were much more at risk than men, from both over-
      and undernutrition perspectives. Both the underlying gender-related and sex
      linked biological determinants of this remarkable double burden of malnutrition
      inequality must be addressed to promote gender equity in health.

PMID- 27049695
TI  - Physical activity preferences, motivators, barriers and attitudes of adults with
      mental illness.
AB  - BACKGROUND: Adults with mental illness may have specific attitudes toward
      physical activity (PA). AIMS: To assess the PA attitudes of non-institutionalised
      adults with mental illness, and associations with psychological distress. METHOD:
      Participants completed questionnaires on activity preferences (type, context and
      sources of support), motivators, barriers and attitudes toward personal training
      (PT). Relationships between responses and distress were assessed using logistic
      regressions. RESULTS: One-hundred forty-two participants completed the
      questionnaires. PA context preferences included activities done close to home,
      outdoors, with professional instruction, with people of the same ability, as part
      of a healthy lifestyle program and with a social component. The most commonly
      endorsed source of support was an exercise instructor. Most respondents had never
      received PT; however, PT had high acceptability. Common barriers included poor
      physical and mental health, and lack of money. Distress was positively associated
      with barriers of poor mental health, tiredness, disorganisation, exhaustion and
      being shy/embarrassed (p <= 0.001). CONCLUSIONS: Local outdoor walking groups
      that include social and healthy lifestyle components, and that are led by an
      exercise instructor who can provide support for overcoming barriers, may best
      meet PA interests of this group. PT could be an acceptable method for offering
      individualised support.

PMID- 27049696
TI  - Magnetic correlates in electromagnetic consciousness.
AB  - We examine the hypothesis that consciousness is a manifestation of the
      electromagnetic field, finding supportive factors not previously considered. It
      is not likely that traditional electrophysiological signaling modes can be
      readily transmitted throughout the brain to properly enable this field because of
      electric field screening arising from the ubiquitous distribution of high
      dielectric lipid membranes, a problem that vanishes for low-frequency magnetic
      fields. Many reports over the last few decades have provided evidence that living
      tissue is robustly sensitive to ultrasmall (1-100 nT) ELF magnetic fields
      overlapping the gamma-frequency range often associated with awareness. An example
      taken from animal behavior (coherent bird flocking) lends support to the
      possibility of a disembodied electromagnetic consciousness. In contrast to
      quantum consciousness hypotheses, the present approach is open to experimental
      trial. 

PMID- 27049697
TI  - Impact of time-of-flight on indirect 3D and direct 4D parametric image
      reconstruction in the presence of inconsistent dynamic PET data.
AB  - Kinetic parameter estimation in dynamic PET suffers from reduced accuracy and
      precision when parametric maps are estimated using kinetic modelling following
      image reconstruction of the dynamic data. Direct approaches to parameter
      estimation attempt to directly estimate the kinetic parameters from the measured
      dynamic data within a unified framework. Such image reconstruction methods have
      been shown to generate parametric maps of improved precision and accuracy in
      dynamic PET. However, due to the interleaving between the tomographic and kinetic
      modelling steps, any tomographic or kinetic modelling errors in certain regions
      or frames, tend to spatially or temporally propagate. This results in biased
      kinetic parameters and thus limits the benefits of such direct methods. Kinetic
      modelling errors originate from the inability to construct a common single
      kinetic model for the entire field-of-view, and such errors in erroneously
      modelled regions could spatially propagate. Adaptive models have been used within
      4D image reconstruction to mitigate the problem, though they are complex and
      difficult to optimize. Tomographic errors in dynamic imaging on the other hand,
      can originate from involuntary patient motion between dynamic frames, as well as
      from emission/transmission mismatch. Motion correction schemes can be used,
      however, if residual errors exist or motion correction is not included in the
      study protocol, errors in the affected dynamic frames could potentially propagate
      either temporally, to other frames during the kinetic modelling step or
      spatially, during the tomographic step. In this work, we demonstrate a new
      strategy to minimize such error propagation in direct 4D image reconstruction,
      focusing on the tomographic step rather than the kinetic modelling step, by
      incorporating time-of-flight (TOF) within a direct 4D reconstruction framework.
      Using ever improving TOF resolutions (580 ps, 440 ps, 300 ps and 160 ps), we
      demonstrate that direct 4D TOF image reconstruction can substantially prevent
      kinetic parameter error propagation either from erroneous kinetic modelling,
      inter-frame motion or emission/transmission mismatch. Furthermore, we demonstrate
      the benefits of TOF in parameter estimation when conventional post-reconstruction
      (3D) methods are used and compare the potential improvements to direct 4D
      methods. Further improvements could possibly be achieved in the future by
      combining TOF direct 4D image reconstruction with adaptive kinetic models and
      inter-frame motion correction schemes.

PMID- 27049698
TI  - PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO,
      MINAS GERAIS STATE, BRAZIL.
AB  - Despite public health campaigns and epidemiological surveillance activities,
      Chagas disease remains a major health problem in Latin America. According to data
      from the World Health Organization, there are approximately 7-8 million people
      infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin
      America. This study aims to examine the serological profile of blood donors in
      blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas
      Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which
      were grouped according to gender and age. Sample collections were performed from
      January 1991 to December 2011, and 277 donors (0.5%) were considered
      serologically ineligible due to Chagas disease. Analysis of data showed no
      significant difference between genders. As for age, the highest proportion of
      ineligible donors was from 40 to 49 years (30%), and there was a positive
      correlation between increasing age and the percentage of patients seropositive
      for Chagas disease. Therefore, adopting strategies that allow the safe
      identification of donors with positive serology for Chagas disease is essential
      to reduce or eliminate indeterminate serological results. 

PMID- 27049699
TI  - PATHOGENICITY OF Blastocystis sp. TO THE GASTROINTESTINAL TRACT OF MICE:
      RELATIONSHIP BETWEEN INOCULUM SIZE AND PERIOD OF INFECTION.
AB  - The pathogenic potential of Blastocystis sp. in experimental models requires
      further investigation. In this work, the pathogenicity of this parasite in the
      gastrointestinal tract of male Swiss mice was evaluated according to the inoculum
      size and period of infection. Animals were infected intragastrically, with 100,
      500, 1,000, 5,000 and 10,000 Blastocystis sp. vacuolar forms obtained from a
      mixture of eight human isolates cultured axenically in Jones' medium. After
      seven, 14, 21, 28 and 60 days of infection, the animals were sacrificed and
      fragments of the small intestine (duodenum), large intestine, and cecum were
      subjected to histopathological analysis. Blastocystis sp. triggered an
      inflammatory response in the different tissues analyzed, with a predominance of
      mononuclear cells. The parasite was found in the muscular layer of the cecum,
      showing its invasive character. Larger inocula triggered inflammatory processes
      earlier (seven days) than smaller ones (from 21 days). We conclude that, in the
      proposed model, the pathogenicity of Blastocystis sp. isolates that were studied
      is related to inoculum size and period of infection. 

PMID- 27049700
TI  - MOLLUSCICIDAL AND LARVICIDAL ACTIVITIES OF Atriplex inflata AERIAL PARTS AGAINST
      THE MOLLUSK Galba truncatula, INTERMEDIATE HOST OF Fasciola hepatica.
AB  - Fasciolosis is a widespread parasitosis of farm live-stock in many developing
      countries. For this reason, it is necessary to search for new substances against
      parasitic diseases caused by flukes. Indeed, a wide variety of terrestrial plants
      have been subjected to chemical and pharmacological screening in order to
      discover their potential for human medicinal use. The molluscicidal and
      larvicidal activities of Atriplex inflata were tested on Galba truncatula and
      Fasciola hepatica larval stages infecting this snail in Tunisia. Phytochemical
      tests were conducted on extracts in order to establish a meaningful relationship
      with molluscicidal and larvicidal activities. The molluscicidal activity was
      evaluated by subjecting snails to sample aqueous solutions. Accordingly, hexane,
      ethyl acetate, methanol and methanol-water (8:2, v-v) were used as extraction
      solvents. As a result, hexane and ethyl acetate extracts showed potent activity,
      according to the World Health Organization, giving LC50 = 7.59 mg/L and 6.69 mg/L
      for hexane extracts of leaves and fruits, respectively. Ethyl acetate extracts
      gave LC50 = 5.90 mg/L and 7.32 mg/L for leaves and fruits, successively.
      Molluscicidal activities of powders were less potent on snails, but active
      according to the World Health Organization. Hexane and ethyl acetate extracts
      from leaves and fruits gave potent larvicidal activities with a delay rate
      exceeding 45.50% (45.50- 98.92%). Phytochemical tests showed that these
      activities may be attributed to the presence of triterpenoids and/or sterols. 

PMID- 27049701
TI  - CHEMOPROPHYLAXIS TO CONTROL LEPROSY AND THE PERSPECTIVE OF ITS IMPLEMENTATION IN
      BRAZIL: A PRIMER FOR NON-EPIDEMIOLOGISTS.
AB  - The occurrence of leprosy has decreased in the world but the perspective of its
      elimination has been questioned. A proposed control measure is the use of post
      exposure chemoprophylaxis (PEP) among contacts, but there are still questions
      about its operational aspects. In this text we discuss the evidence available in
      literature, explain some concepts in epidemiology commonly used in the research
      on this topic, analyze the appropriateness of implementing PEP in the context of
      Brazil, and answer a set of key questions. We argue some points: (1) the number
      of contacts that need to receive PEP in order to prevent one additional case of
      disease is not easy to be generalized from the studies; (2) areas covered by the
      family health program are the priority settings where PEP could be implemented;
      (3) there is no need for a second dose; (4) risk for drug resistance seems to be
      very small; (5) the usefulness of a serological test to identify a higher risk
      group of individuals among contacts is questionable. Given that, we recommend
      that, if it is decided to start PEP in Brazil, it should start on a small scale
      and, as new evidence can be generated in terms of feasibility, sustainability and
      impact, it could move up a scale, or not, for a wider intervention. 

PMID- 27049702
TI  - DENGUE OUTBREAK IN MATO GROSSO STATE, MIDWESTERN BRAZIL.
AB  - Dengue virus (DENV) is the most frequent arbovirus worldwide. In this study, we
      report a large outbreak in Mato Grosso State (MT). Serum samples from 604
      patients with acute febrile illness for less than five days were inoculated in
      C6/36 cells, then infected cells were subjected to an indirect immunofluorescence
      test for DENV serotypes and yellow fever virus. Serum samples were submitted to a
      multiplex-semi-nested-RT-PCR for 11 flaviviruses. DENV-4 was isolated in 150/604
      (24.8%) and DENV-1 in 19/604 (3.1%) specimens. By RT-PCR, 331 (54.8%) samples
      tested positive for DENV; 321 had single infections (DENV-4 n = 305; DENV-1 n =
      15; DENV-3 n = 1), nine had co-infections of DENV-1/DENV-4, and one of DENV
      2/DENV-4. DENV-4 was detected in 315/331 (95.2%) positive patients from 17
      municipalities, and DENV-1 in 24/331 (7.2%) patients from five cities in north
      central MT and the city of Cuiaba. The incidence of infection was higher in
      patients aged 20-39 (142/331; 42.9%). The NS5 partial nucleotide sequence of DENV
      1 was most similar to that of genotype V, DENV-2 to Southeast Asian/American,
      DENV-3 to genotype III, and DENV-4 to genotype II strains, considered the most
      frequent strains in Brazil. This outbreak coincided with the introduction of DENV
      4 in the state. Cuiaba was hyperendemic for the four DENV serotypes, highlighting
      the necessity for arbovirus surveillance in MT. 

PMID- 27049703
TI  - VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE
      BRAZILIAN AMAZON.
AB  - The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and
      2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made
      this a priority area for studies on this zoonosis. Given this, the present study
      provides data on this phenomenon in an urban context, in order to assess the
      possible circulation of the classic rabies virus (RABV) among bat species in
      Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist
      nets during the wet and dry seasons. Samples of brain tissue and blood were
      collected for virological and serological survey, respectively. None of the 153
      brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95%
      CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus
      planirostris was the most common species, with a high percentage of seropositive
      individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of
      seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f.
      = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96
      62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none
      of the brain tissue samples tested positive for infection, the high proportion of
      seropositive specimens indicates that RABV may be widespread in this urban area. 

PMID- 27049704
TI  - MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF
      ELEVEN CASES AND REVIEW OF THE LITERATURE.
AB  - Neurological complications of varicella-zoster virus (VZV) are infrequent and
      include various clinical pictures. The reactivation of VZV in patients with AIDS
      is generally associated with an acute and severe meningoencephalitis. We report
      the epidemiological, clinical and virological data from 11 consecutive patients
      with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to
      VZV. All patients were male and seropositive for HIV. The primary risk factor for
      HIV infection was unprotected sexual contact. The median of CD4 T cell count was
      142 cells/uL. All of them presented signs and symptoms of meningoencephalitis.
      Six patients (54.5%) presented pleocytosis; they all showed high CSF protein
      concentrations with a median of 2.1 g/dL. Polymerase chain reaction of
      cerebrospinal fluid specimen was positive for VZV in all of them and they were
      treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall
      survival was 63% (7 of 11 patients). The four dead patients had low cellular
      counts in CSF, below the median of this parameter. VZV should be included among
      the opportunistic pathogens that can involve CNS with a diffuse and severe
      meningoencephalitis in patients with advanced HIV/AIDS disease. 

PMID- 27049705
TI  - ANTIFUNGAL ACTIVITY OF Cymbopogon nardus (L.) Rendle (CITRONELLA) AGAINST
      Microsporum canis FROM ANIMALS AND HOME ENVIRONMENT.
AB  - Dermatophytosis is a common zoonosis in urban centers. Dogs and cats have played
      an important role as its disseminators. Environmental decontamination is
      essential for the prevention of its propagation to humans and animals. However,
      sanitizers or disinfectants with antifungal activity, currently available, have
      high toxicity. The present study evaluated the in vitro effects of an extract of
      citronella (Cymbopogon nardus) on 31 Microsporum canis isolates from animals and
      home environments. Susceptibility tests were performed based on document M38-A2
      (2008) of the Clinical and Laboratory Standards Institute with modifications for
      natural products. Although susceptibility variation was observed between the
      fungus tested, the concentrations that inhibited the growth of 50 and 90% of the
      microorganisms were low (19.5 and 78 ug/mL, respectively). Thus, this citronella
      extract showed potent fungistatic and fungicide activities against M. canis
      isolated from animals and home environments. Therefore, it could be an
      alternative for dermatophytosis prophylaxis in the home environment. 

PMID- 27049706
TI  - Pseudomonas spp. ISOLATED FROM THE ORAL CAVITY OF HEALTHCARE WORKERS FROM AN
      ONCOLOGY HOSPITAL IN MIDWESTERN BRAZIL.
AB  - This cross-sectional study, performed in an oncology hospital in Goiania, aimed
      to characterize the prevalence of oral colonization and antimicrobial
      susceptibility of Pseudomonas spp. isolated from the saliva of healthcare
      workers. Microorganisms were subjected to biochemical tests, susceptibility
      profile, and phenotypic detection. Of 76 participants colonized with Gram
      negative bacilli, 12 (15.8%) harbored Pseudomonas spp. Of all isolates, P.
      aeruginosa (75.0%), P. stutzeri (16.7%), and P. fluorescens (8.3%), were
      resistant to cefoxitin, and therefore likely to be AmpC producers. The results
      are clinically relevant and emphasize the importance of surveillance to minimize
      bacterial dissemination and multiresistance. 

PMID- 27049707
TI  - EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS.
AB  - Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides
      brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There
      are few reports in the literature about the disease damages during pregnancy and
      the consequences to the fetuses and breeding. This study evaluated the
      implications of PCM during pregnancy on offspring and mothers in Wistar rats.
      Groups of rats were submitted to systemic Pb infection, by intraperitoneal
      infusion, and mated 30 days after the infection date. Immediately after birth,
      rats and neonates were sacrificed to obtain organs for standard histological
      examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of
      anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however,
      the fetuses from infected pregnant rats had lower body and organ weight but the
      fertility rate was 100%. The largest number of CFU was recovered from the organ
      of pregnant rats, the pathological examination revealed more severe infection in
      the same group, further on the largest number of granulomas and fungal field. It
      can be concluded that the PCM was more severe in the group of pregnant rats, with
      implications to the weight of offspring. 

PMID- 27049708
TI  - HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL
      RESPONSE AFTER HEPATITIS C TREATMENT.
AB  - Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for
      the development of liver cirrhosis and hepatocellular carcinoma. However, the
      emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients,
      especially after sustained virological response (SVR) is an unusual event.
      Recently, it has been suggested that HCV genotype 3 may have a particular
      oncogenic mechanism, but the factors involved in these cases as well as the
      profile of these patients are still not fully understood. Thus, we present the
      case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who
      developed HCC two years after treatment with pegylated-interferon and ribavirin,
      with SVR, in Brazil. 

PMID- 27049709
TI  - ACUTE TOXOPLASMOSIS IN A BREASTFED INFANT WITH POSSIBLE TRANSMISSION BY WATER.
AB  - Toxoplasma gondii transmission via breastfeeding has been discussed; however, no
      cases have been confirmed to date. This article describes a case of acute
      toxoplasmosis diagnosed in a mother and her six-month-old breastfed infant. The
      study accounts for the possibility of breast milk transmission and directs both
      clinicians and pediatricians to the hypothesis that both patients acquired
      toxoplasmosis via water ingestion. 

PMID- 27049710
TI  - DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV
      NEGATIVE BRAZILIAN PATIENTS.
AB  - Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic
      in Brazil. Disseminated clinical forms are uncommon in immunocompetent
      individuals. We describe two HIV-negative patients with disseminated fungal
      infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by
      biopsies of suprarenal lesions. Both were treated for a prolonged period with
      oral antifungal agents, and both showed favorable outcomes. 

PMID- 27049711
TI  - CHAGASIC MENINGOENCEPHALITIS IN AN HIV INFECTED PATIENT WITH MODERATE
      IMMUNOSUPPRESSION: PROLONGED SURVIVAL AND CHALLENGES IN THE HAART ERA.
AB  - The reactivation of Chagas disease in HIV infected patients presents high
      mortality and morbidity. We present the case of a female patient with confirmed
      Chagasic meningoencephalitis as AIDS-defining illness. Interestingly, her TCD4+
      lymphocyte cell count was 318 cells/mm3. After two months of induction therapy,
      one year of maintenance with benznidazol, and early introduction of highly active
      antiretroviral therapy (HAART), the patient had good clinical, parasitological
      and radiological evolution. We used a qualitative polymerase chain reaction for
      the monitoring of T. cruzi parasitemia during and after the treatment. We
      emphasize the potential value of molecular techniques along with clinical and
      radiological parameters in the follow-up of patients with Chagas disease and HIV
      infection. Early introduction of HAART, prolonged induction and maintenance of
      antiparasitic therapy, and its discontinuation are feasible, in the current
      management of reactivation of Chagas disease. 

PMID- 27049712
TI  - MOLECULAR IDENTIFICATION OF Pseudoterranova azarasi LARVAE IN COD (Gadus sp.)
      SOLD FOR HUMAN CONSUMPTION IN BRAZIL.
AB  - Anisakiasis and Pseudoterranovosis are human diseases caused by the ingestion of
      live Anisakidae larvae in raw, undercooked or lightly marinated fish. Larvae were
      collected from one salted cod sold for human consumption in a Sao Paulo market in
      2013. One section of one brownish larva was used for molecular analyses. The
      partial COX2 gene sequence from the larva had a nucleotide identity of 99.8 %
      with Pseudoterranova azarasi, which belongs to the Pseudoterranova decipiens
      species complex. The risk of allergy when consuming dead larvae in salted fish is
      not well known and should be considered. 

PMID- 27049713
TI  - RESPONSE OF Culex quinquefasciatus LARVAE TO THREE INSECTICIDES.

PMID- 27049714
TI  - The Risks and Benefits of Conducting Sensitive Research to Understand Parental
      Experiences of Caring for Infants With Hypoxic-Ischemic Encephalopathy.
AB  - AIM: The aim of this report is to describe the parental experience of the
      emotional and physical risks and participant burden of participation in sensitive
      research about caring for an infant with hypoxic-ischemic encephalopathy.
      BACKGROUND: Protecting the ethical rights of participants in research is a main
      focus of investigators. Evaluating the effect of current methods employed to
      protect participants in sensitive research is necessary to determine if the
      participants' ethical rights are protected. Little research has addressed the
      parental perspective of participating in sensitive research. DESIGN: The design
      of this study is a qualitative, descriptive methodology with structured
      interviews with parents. METHODS: Participants were asked to describe their
      experience of participating in sensitive research. The qualitative data collected
      were analyzed using content analysis. Interviews were conducted between July 2010
      and February 2012. RESULTS: Thirteen parents of infants with hypoxic-ischemic
      encephalopathy were interviewed. Parents did not report harm or participant
      burden. Most of these parents found continued participation to be beneficial
      because they could express intense emotions in a nonjudgmental environment and
      also reflect on the milestones their child has reached since the traumatic birth
      experience. CONCLUSIONS: This study provides additional evidence to researchers
      regarding the risks and benefits to participants in sensitive research studies.
      Individuals are willing to participate in sensitive research, even during
      stressful times in their lives. The interviews allow participants an outlet to
      discuss thoughts and feelings and to reflect on past events and gain perspective.
      Participants do not report experiencing harm when participating in interviews
      about sensitive research.

PMID- 27049715
TI  - Prevention of Ventilator-Associated Pneumonia in the Intensive Care Unit: Beyond
      the Basics.
AB  - Ventilated-associated pneumonia (VAP) is a major concern for hospitals and a
      major problem for ventilated patients in the intensive care unit. Included in the
      basics are hand hygiene, wearing gloves, endotracheal tube suctioning, head of
      bed at 30 degrees , stress ulcer prophylaxis, turning patient side to side at
      least every two hours, and giving the patient a sedation vacation each morning.
      Beyond the basics included here are oral hygiene, oral suctioning, endotracheal
      tube cuff pressure, artificial humidification, the difference in practice between
      registered nurses and respiratory therapists, using the beach chair position and
      early mobilization, and the VAP bundle. The prevention of VAP becomes the focus
      for both nurses and respiratory therapists working with patients who are
      ventilated. 

PMID- 27049716
TI  - Magnobovatol inhibits smooth muscle cell migration by suppressing PDGF-Rbeta
      phosphorylation and inhibiting matrix metalloproteinase-2 expression.
AB  - The migration of vascular smooth muscle cells (VSMCs) may play a crucial role in
      the pathogenesis of vascular diseases, such as atherosclerosis and post
      angioplasty restenosis. Platelet-derived growth factor (PDGF)-BB is a potent
      mitogen for VSMCs and plays an important role in the intimal accumulation of
      VSMCs. Magnobovatol, a new neolignan from the fruits of Magnolia obovata, has
      been shown to have anticancer properties. However, the effects of magnobovatol on
      VSMCs are unknown. In the present study, we examined the effects of magnobovatol
      on the PDGF-BB-induced migration of mouse and human VSMCs, as well as the
      underlying mechanisms. Magnobovatol significantly inhibited the PDGF-BB-induced
      migration of mouse and human VSMCs without inducing cell death (as shown by MTT
      assay and wound healing assay). Additionally, we demonstrated that magnobovatol
      significantly blocked the PDGF-BB-induced phosphorylation of the PDGF receptor
      (PDGF-R), Akt and extracellular signal-regulated kinase (ERK)1/2 by inhibiting
      the activation of the PDGF-BB signaling pathway. Moreover, in both mouse and
      human VSMCs, magnobovatol inhibited PDGF-induced matrix metalloproteinase (MMP)-2
      expression at the mRNA and protein level, as well as the proteolytic activity of
      MMP-2 (as shown by western blot analysis, RT-PCR, gelatin zymography and ELISA).
      In addition, the sprout outgrowth formation of aortic rings induced by PDGF-BB
      was inhibited by magnobovatol (as shown by aortic ring assay). Taken together,
      our findings indicate that magnobovatol inhibits VSMC migration by decreasing MMP
      2 expression through PDGF-R and the ERK1/2 and Akt pathways. Our data may improve
      the understanding of the anti-atherogenic effects of magnobovatol in VSMCs.

PMID- 27049717
TI  - High fat diet increases melanoma cell growth in the bone marrow by inducing
      osteopontin and interleukin 6.
AB  - The impact of metabolic stress induced by obesity on the bone marrow melanoma
      niche is largely unknown. Here we employed diet induced obese mice model, where
      mice received high-fat (HFD) or normal diet (ND) for 6 weeks before challenge
      with B16F10 melanoma cells. Tumor size, bone loss and osteoclasts numbers were
      assessed histologically in the tibial bones. For defining the molecular pathway,
      osteopontin knock-out mice, interleukin 6 neutralizing antibody or Janus kinase 2
      inhibition were carried out in the same model. Mechanistic studies such as
      adipocyte-melanoma co-cultures for defining adipocyte induced changes of tumor
      cell proliferation and expression profiles were also performed. As results, HFD
      enhanced melanoma burden in bone by increasing tumor area and osteoclast numbers.
      This process was associated with higher numbers of bone marrow adipocytes
      expressing IL-6 in direct vicinity to tumor cells. Inhibition of IL-6 or of
      downstream JAK2 blocked HFD-induced tumor progression. Furthermore, the
      phenotypic changes of melanoma cells triggered macrophage and osteoclast
      accumulation accompanied by increased osteopontin expression. Osteopontin
      triggered osteoclastogenesis and also exerted a positive feedback loop to tumor
      cells, which was abrogated in its absence. Metabolic stress by HFD promotes
      melanoma growth in the bone marrow by an increase in bone marrow adipocytes and
      IL-6-JAK2-osteopontin mediated activation of tumor cells and osteoclast
      differentiation. 

PMID- 27049718
TI  - Associations of potentially functional variants in IL-6, JAKs and STAT3 with
      gastric cancer risk in an eastern Chinese population.
AB  - The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in
      inflammation-mediated cancers, including gastric cancer (GCa). We evaluated
      associations between 10 potentially functional single nucleotide polymorphisms
      (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125
      GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa
      risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios
      (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and
      JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA
      + AA vs. GG). We also found that a significant decreased GCa risk was associated
      with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99
      for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A
      variant risk genotypes revealed that individuals with one-or-two risk genotypes
      exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59).
      Genotypes and mRNA expression correlation analysis using the data from the HapMap
      3 database provided further support for the observed risk associations. Larger
      studies are warranted to validate these findings. 

PMID- 27049719
TI  - Niclosamide enhances abiraterone treatment via inhibition of androgen receptor
      variants in castration resistant prostate cancer.
AB  - Considerable evidence from both clinical and experimental studies suggests that
      androgen receptor variants, particularly androgen receptor variant 7 (AR-V7), are
      critical in the induction of resistance to enzalutamide and abiraterone. In this
      study, we investigated the role of AR-V7 in the cross-resistance of enzalutamide
      and abiraterone and examined if inhibition of AR-V7 can improve abiraterone
      treatment response. We found that enzalutamide-resistant cells are cross
      resistant to abiraterone, and that AR-V7 confers resistance to abiraterone. Knock
      down of AR-V7 by siRNA in abiraterone resistant CWR22Rv1 and C4-2B MDVR cells
      restored their sensitivity to abiraterone, indicating that AR-V7 is involved in
      abiraterone resistance. Abiraterone resistant prostate cancer cells generated by
      chronic treatment with abiraterone showed enhanced AR-V7 protein expression.
      Niclosamide, an FDA-approved antihelminthic drug that has been previously
      identified as a potent inhibitor of AR-V7, re-sensitizes resistant cells to
      abiraterone treatment in vitro and in vivo. In summary, this preclinical study
      suggests that overexpression of AR-V7 contributes to resistance to abiraterone,
      and supports the development of combination of abiraterone with niclosamide as a
      potential treatment for advanced castration resistant prostate cancer. 

PMID- 27049720
TI  - Brachyury as a potential modulator of androgen receptor activity and a key player
      in therapy resistance in prostate cancer.
AB  - Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second
      leading cause of cancer-related deaths in men. Acquisition of resistance to
      conventional therapy is a major problem for PCa patient management. Several
      mechanisms have been described to promote therapy resistance in PCa, such as
      androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT),
      acquisition of stem cell properties and neuroendocrine transdifferentiation
      (NEtD). Recently, we identified Brachyury as a new biomarker of PCa
      aggressiveness and poor prognosis. In the present study we aimed to assess the
      role of Brachyury in PCa therapy resistance. We showed that Brachyury
      overexpression in prostate cancer cells lines increased resistance to docetaxel
      and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy
      resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a
      direct regulator of AR expression as well as of the biomarker AMACR and the
      mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was
      also able to increase EMT and stem properties. By in silico analysis, clinically
      human Brachyury-positive PCa samples were associated with biomarkers of PCa
      aggressiveness and therapy resistance, including PTEN loss, and expression of
      NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury
      contributes to tumor chemotherapy resistance, constituting an attractive target
      for advanced PCa patients. 

PMID- 27049721
TI  - Tissue repair genes: the TiRe database and its implication for skin wound
      healing.
AB  - Wound healing is an inherent feature of any multicellular organism and recent
      years have brought about a huge amount of data regarding regular and abnormal
      tissue repair. Despite the accumulated knowledge, modulation of wound healing is
      still a major biomedical challenge, especially in advanced ages. In order to
      collect and systematically organize what we know about the key players in wound
      healing, we created the TiRe (Tissue Repair) database, an online collection of
      genes and proteins that were shown to directly affect skin wound healing. To
      date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus
      norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of
      skin wound healing-associated genes showed that skin wound healing genes are (i)
      over-conserved among vertebrates, but are under-conserved in invertebrates; (ii)
      enriched in extracellular and immuno-inflammatory genes; and display (iii) high
      interconnectivity and connectivity to other proteins. The latter may provide
      potential therapeutic targets. In addition, a slower or faster skin wound healing
      is indicative of an aging or longevity phenotype only when assessed in advanced
      ages, but not in the young. In the long run, we aim for TiRe to be a one-station
      resource that provides researchers and clinicians with the essential data needed
      for a better understanding of the mechanisms of wound healing, designing new
      experiments, and the development of new therapeutic strategies. TiRe is freely
      available online at http://www.tiredb.org. 

PMID- 27049722
TI  - Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and
      growth in ALK-positive neuroblastoma cells, Drosophila and mice.
AB  - Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor which has been
      implicated in numerous solid and hematologic cancers. ALK mutations are reported
      in about 5-7% of neuroblastoma cases but the ALK-positive percentage increases
      significantly in the relapsed patient population. Crizotinib, the first
      clinically approved ALK inhibitor for the treatment of ALK-positive lung cancer
      has had less dramatic responses in neuroblastoma. Here we investigate the
      efficacy of a second-generation ALK inhibitor, brigatinib, in a neuroblastoma
      setting. Employing neuroblastoma cell lines, mouse xenograft and Drosophila
      melanogaster model systems expressing different constitutively active ALK
      variants, we show clear and efficient inhibition of ALK activity by brigatinib.
      Similar abrogation of ALK activity was observed in vitro employing a set of
      different constitutively active ALK variants in biochemical assays. These results
      suggest that brigatinib is an effective inhibitor of ALK kinase activity in ALK
      addicted neuroblastoma that should be considered as a potential future
      therapeutic option for ALK-positive neuroblastoma patients alone or in
      combination with other treatments. 

PMID- 27049723
TI  - BCL2-BH4 antagonist BDA-366 suppresses human myeloma growth.
AB  - Multiple myeloma (MM) is a heterogeneous plasma cell malignancy and remains
      incurable. B-cell lymphoma-2 (BCL2) protein correlates with the survival and the
      drug resistance of myeloma cells. BH3 mimetics have been developed to disrupt the
      binding between BCL2 and its pro-apoptotic BCL2 family partners for the treatment
      of MM, but with limited therapeutic efficacy. We recently identified a small
      molecule BDA-366 as a BCL2 BH4 domain antagonist, converting it from an anti
      apoptotic into a pro-apoptotic molecule. In this study, we demonstrated that BDA
      366 induces robust apoptosis in MM cell lines and primary MM cells by inducing
      BCL2 conformational change. Delivery of BDA-366 substantially suppressed the
      growth of human MM xenografts in NOD-scid/IL2Rgammanull mice, without significant
      cytotoxic effects on normal hematopoietic cells or body weight. Thus, BDA-366
      functions as a novel BH4-based BCL2 inhibitor and offers an entirely new tool for
      MM therapy. 

PMID- 27049724
TI  - Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non
      small cell lung cancer.
AB  - MicroRNAs are a class of non-coding single-stranded RNA, 20-23 nucleotide in
      length, which can be involved in the regulation of gene expression. Through
      binding with 3'-untranslated regions (3'-UTR), microRNAs can cause degradation of
      target mRNAs or inhibition of translation, and thus regulating the expression of
      genes at the post-transcriptional level. In this study, we found that miR-486-5p
      was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and
      cell lines, suggesting that miR-486-5p might function as a tumor suppressor in
      lung cancer. Additionally, we showed that CDK4, an oncogene that plays an
      important role in cell cycle G1/S phase progression, was directly targeted by miR
      486-5p. Furthermore, our data reveals that knockdown of CDK4 by siRNA can inhibit
      cell proliferation, promote apoptosis, and impede cell-cycle progression. In
      epigenetics, the upstream promoter of miR-486-5p was strongly regulated by
      methylation in NSCLC. Collectively, our results suggest that miR-486-5p could not
      only inhibit NSCLC by downregulating the expression of CDK4, but also be as a
      promising and potent therapy in the near future. 

PMID- 27049725
TI  - Human platelets repurposed as vehicles for in vivo imaging of myeloma
      xenotransplants.
AB  - Human platelets were identified in tumors by Trousseau in 1865, although their
      roles in tumor microenvironments have only recently attracted the attention of
      cancer researchers. In this study we exploit and enhance platelet interactions in
      tumor microenvironments by introducing tumor-targeting and imaging functions. The
      first step in repurposing human platelets as vehicles for tumor-targeting was to
      inhibit platelet-aggregation by cytoplasmic-loading of kabiramide (KabC), a
      potent inhibitor of actin polymerization and membrane protrusion. KabC-Platelets
      can accumulate high levels of other membrane-permeable cytoxins and probes,
      including epidoxorubicin, carboxyfluorescein di-ester and chlorin-e6. Finally,
      mild reaction conditions were developed to couple tumor-targeting proteins and
      antibodies to KabC-platelets. Fluorescence microscopy studies showed KabC
      platelets, surface-coupled with transferrin and Cy5, bind specifically to
      RPMI8226 and K562 cells, both of which over-express the transferrin receptor.
      Repurposed platelets circulate for upto 9-days a feature that increases their
      chance of interacting with target cells. KabC-platelets, surface-coupled with
      transferrin and Cy7, or chlorin-e6, and injected in immuno-compromised mice were
      shown to accumulate specifically in sub-cutaneous and intra-cranial myeloma
      xenotransplants. The high-contrast, in vivo fluorescence images recorded from
      repurposed platelets within early-stage myeloma is a consequence in part of their
      large size (phi~2um), which allows them to transport 100 to 1000-times more
      targeting-protein and probe molecules respectively. Human platelets can be
      configured with a plurality of therapeutic and targeting antibodies to help stage
      tumor environments for an immunotherapy, or with combinations of therapeutic
      antibodies and therapeutic agents to target and treat cardiovascular and
      neurologic diseases. 

PMID- 27049726
TI  - Adipogenic miRNA and meta-signature miRNAs involved in human adipocyte
      differentiation and obesity.
AB  - MicroRNAs (miRNAs) have been identified as a new class of regulatory molecules
      that influence many biological functions, including metabolism, adipocyte
      differentiation. To determine the role of adipogenic miRNAs in the adipocyte
      differentiation process, we used microarray technology to monitor miRNA levels in
      human adipose-derived mesenchymal stem cells (hMSCs-Ad), human stromal vascular
      cells (SVCs) and differentiated adipocytes. 79 miRNAs were found to be
      differentially expressed, most of which are located in obesity related
      chromosomal regions but have not been previously linked to adipocyte
      differentiation process. A systematic search was made for relevant studies in
      academic data bases, involving the Gene Expression Omnibus (GEO) ArrayExpress,
      Pubmed and Embase database. Eight studies on human adipocyte differentiation or
      obesity were included in the final analysis. After combining our microarray data
      with meta-analysis of published microarray data, we detected 42 differently
      expressed miRNAs (meta-signature miRNAs) in mature adipocytes compared to SVCs or
      hMSCs-Ad. Our study shows meta-signature miRNAs specific for adipogenesis,
      several of which are correlated with key gene targets demonstrating functional
      relationships to pathways in BMP signaling pathway, Cell differentiation, Wnt
      signaling, insulin receptor signaling pathway, MAPK signaling, Cell cycle and
      lipid metabolic process. Our study shows that the first evidence of hsa-let-7
      family, hsa-miR-15a-5p, hsa-miR-27a-3p, hsa-miR-106b-5p, hsa-miR-148a-3p and hsa
      miR-26b-5p got a great weight in adipogenesis. We concluded that meta-signature
      miRNAs involved in adipocyte differentiation and provided pathophysiological
      roles and novel insight into obesity and its related metabolic diseases.

PMID- 27049727
TI  - The emerging roles and therapeutic potential of cyclin-dependent kinase 11
      (CDK11) in human cancer.
AB  - Overexpression and/or hyperactivation of cyclin-dependent kinases (CDKs) are
      common features of most cancer types. CDKs have been shown to play important
      roles in tumor cell proliferation and growth by controlling cell cycle,
      transcription, and RNA splicing. CDK4/6 inhibitor palbociclib has been recently
      approved by the FDA for the treatment of breast cancer. CDK11 is a
      serine/threonine protein kinase in the CDK family and recent studies have shown
      that CDK11 also plays critical roles in cancer cell growth and proliferation. A
      variety of genetic and epigenetic events may cause universal overexpression of
      CDK11 in human cancers. Inhibition of CDK11 has been shown to lead to cancer cell
      death and apoptosis. Significant evidence has suggested that CDK11 may be a novel
      and promising therapeutic target for the treatment of cancers. This review will
      focus on the emerging roles of CDK11 in human cancers, and provide a proof-of
      principle for continued efforts toward targeting CDK11 for effective cancer
      treatment.

PMID- 27049728
TI  - Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial
      mesenchymal transition of triple-negative breast cancer cells.
AB  - In triple-negative breast cancer (TNBC), the high recurrence rate, increased
      invasion and aggressive metastatic formation dictate patient survival. We
      previously demonstrated a critical role for the Na+/H+ exchanger isoform 1 (NHE1)
      in controlling metastasis of triple-negative cells. Here, we investigated the
      effect of changes to three regulatory loci of NHE1. Two via the
      Ras/Raf/ERK/p90RSK pathway: p90RSK/14-3-3 (S703A) and ERK1/2 (S766,770,771A,
      SSSA) and a third via a calmodulin-binding domain (K641,R643,645,647E, 1K3R4E).
      MDA-MB-231 cells with a mutation at the p90RSK site (S703A-NHE1) changed from a
      wild-type mesenchymal morphology to a smaller epithelial-like phenotype with a
      loss of expression of mesenchymal marker vimentin. S703A cells also had reduced
      metastatic potential and markedly decreased rates of migration, invasion,
      spheroid growth, anchorage-dependent and soft agar colony formation. Similarly,
      BI-D1870, a specific inhibitor of p90RSK, significantly inhibited the metastatic
      potential of highly invasive MDA-MB-231 and moderately invasive MDA-MB-468 TNBC
      cells, but was minimally effective in non-invasive Hs578T TNBC cells. In
      contrast, invasion and spheroid growth were unaffected in cells containing NHE1
      with mutations interfering with its activation by ERK1/2 (SSSA), though rates of
      migration and colony formation were reduced. Cells with a constitutive activation
      of NHE1 via the 1K3R4E mutation exhibited higher rates of migration, invasion,
      and spheroid growth. Taken together, our data demonstrate the critical role of
      NHE1 in metastasis, and suggest a novel link between NHE1 and the expression and
      cytosolic organization of vimentin, a key factor in epithelial-mesenchymal
      transition, that is dependent on p90RSK/14-3-3-mediated activation of the
      exchanger. 

PMID- 27049729
TI  - Circadian factors BMAL1 and RORalpha control HIF-1alpha transcriptional activity
      in nucleus pulposus cells: implications in maintenance of intervertebral disc
      health.
AB  - BMAL1 and RORalpha are major regulators of the circadian molecular oscillator.
      Since previous work in other cell types has shown cross talk between circadian
      rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and
      RORalpha in controlling HIF-1-dependent transcriptional responses in NP cells
      that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent
      HRE reporter activity was further promoted by co-transfection with either BMAL1
      or RORalpha. In addition, stable silencing of BMAL1 or inhibition of RORalpha
      activity resulted in decreased HRE activation. Inhibition of RORalpha also
      modulated HIF1alpha-TAD activity. Interestingly, immunoprecipitation studies
      showed no evidence of BMAL1, CLOCK or RORalpha binding to HIF-1alpha in NP cells.
      Noteworthy, stable silencing of BMAL1 as well as inhibition of RORalpha decreased
      expression of select HIF-1 target genes including VEGF, PFKFB3 and Eno1. To
      delineate if BMAL1 plays a role in maintenance of disc health, we studied the
      spinal phenotype of BMAL1-null mice. The lumbar discs of null mice evidenced
      decreased height, and several parameters associated with vertebral trabecular
      bone quality were also affected in nulls. In addition, null animals showed a
      higher ratio of cells to matrix in NP tissue and hyperplasia of the annulus
      fibrosus. Taken together, our results indicate that BMAL1 and RORalpha form a
      regulatory loop in the NP and control HIF-1 activity without direct interaction.
      Importantly, activities of these circadian rhythm molecules may play a role in
      the adaptation of NP cells to their unique niche. 

PMID- 27049731
TI  - Deep Brain Stimulation for Depression: Keeping an Eye on a Moving Target.

PMID- 27049730
TI  - A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits
      osteosarcoma metastasis in a preclinical model.
AB  - The outcome of patients with metastatic osteosarcoma has not improved since the
      introduction of chemotherapy in the 1970s. Development of therapies targeting the
      metastatic cascade is a tremendous unmet medical need. The Wnt signaling pathway
      has been the focus of intense investigation in osteosarcoma because of its role
      in normal bone development. Although the role of Wnt signaling in the
      pathogenesis of osteosarcoma is controversial, there are several reports of
      dickkopf-1 (DKK-1), a Wnt signaling antagonist, possibly playing a pro
      tumorigenic role. In this work we investigated the effect of anti-DKK-1
      antibodies on the growth and metastasis of patient-derived osteosarcoma
      xenografts. We were able to detect human DKK-1 in the blood of tumor-bearing mice
      and found a correlation between DKK-1 level and tumor proliferation. Treatment
      with the anti-DKK-1 antibody, BHQ880, slowed the growth of orthotopically
      implanted patient-derived osteosarcoma xenografts and inhibited metastasis. This
      effect was correlated with increased nuclear beta-catenin staining and increased
      expression of the bone differentiation marker osteopontin. These findings suggest
      that Wnt signaling is anti-tumorigenic in osteosarcoma, and support the targeting
      of DKK-1 as an anti-metastatic strategy for patients with osteosarcoma. 

PMID- 27049732
TI  - Robotic gait assistive technology as means to aggressive mobilization strategy in
      acute rehabilitation following severe diffuse axonal injury: a case study.
AB  - INTRODUCTION: Diffuse axonal injury is a prominent cause of disablement post
      traumatic brain injury. Utilization of the rapid expansion of our current
      scientific knowledge base combined with greater access to neurological and
      assistive technology as adjuncts to providing sensorimotor experience may yield
      innovative new approaches to rehabilitation based upon a dynamic model of brain
      response following injury. CASE DESCRIPTION: A 24-year-old female who sustained a
      traumatic brain injury, bilateral subdural hemorrhage, subarachnoid hemorrhage
      and severe diffuse axonal injury secondary to a motor vehicle collision.
      DISCUSSION AND CONCLUSIONS: Evidence-based appraisal of present literature
      suggests a link between graded intensity of aerobic activity to facilitation of
      neuro-plastic change and up-regulation of neurotrophins essential to functional
      recovery post-diffuse axonal injury. Following resolution of paroxysmal autonomic
      instability with dystonia, aggressive early mobilization techniques were
      progressed utilizing robotic assistive gait technology in combination with
      conventional therapy. This approach allowed for arguably greater repetition and
      cardiovascular demands across a six-month inpatient rehabilitation stay. Outcomes
      in this case suggest that the use of assistive technology to adjunct higher level
      and intensity rehabilitation strategies may be a safe and effective means towards
      reduction of disablement following severe traumatic brain and neurological
      injury. Implications for Rehabilitation Functional recovery and neuroplasticity
      following diffuse neurological injury involves a complex process determined by
      the sensorimotor experience provided by rehabilitation clinicians. This process
      is in part modulated by intrinsic brain biochemical processes correlated to
      cardiovascular intensity of the activity provided. It is important that
      rehabilitation professionals monitor physiological response to higher intensity
      activities to provide an adaptive versus maladaptive response of central nervous
      system plasticity with activity. Identification of early mobilization parameters
      and skill acquisition may assist selection of gait assistive technology adjunct
      in progressing early optimal physical rehabilitation outcomes in the acute
      inpatient setting.

PMID- 27049733
TI  - Clinical experience with the European Ankylosing Spondylitis Infliximab Cohort
      (EASIC): long-term extension over 7 years with focus on clinical efficacy and
      safety.
AB  - OBJECTIVES: Knowledge on the long-term effects of anti-TNF therapy in patients
      with ankylosing spondylitis (AS) is still limited. Our objective was to study the
      long-term efficacy and safety of anti-TNF therapy in AS. METHODS: After having
      completed the first part of the EASIC trial a total of 71 patients were enrolled
      into this 96-week extension study. Patients were treated with the same dosages
      and dosing intervals of infliximab as in the EASIC core study. Efficacy was
      assessed by using standardised assessment tools such as BASDAI, BASFI, BASMI,
      patient global assessment, CRP levels and the proportion of patients without any
      sign of enthesitis or arthritis. Long-term safety was assessed by documenting
      adverse events (AE), serious adverse events (SAE) and reasons for dropping out.
      RESULTS: Of the 71 patients included, 64 (90.1%) completed the trial , and 7
      discontinued: one was lost to follow-up, 3 withdrew informed consent and in 3
      patients therapy was stopped for different reasons: secondary loss of response,
      recurrent infections and basal cell carcinoma of the skin. The completers showed
      rather stable low scores of BASDAI (mean 2.4, median 2.52), BASFI (mean 3.1,
      median 2.76) and BASMI (mean 3.2, median 3) as well as patients global assessment
      and CRP. The vast majority of patients did not have enthesitis or arthritis. A
      total of 476 AE were observed, 13 of which were SAE. The majority of these were
      infections and most of them affected the respiratory tract. Two malignancies
      occurred: one basal cell carcinoma and one malignant melanoma. These were the
      only SAE judged to be possibly related to the study drug. CONCLUSIONS: Anti-TNF
      treatment with infliximab is efficacious over long periods of time in patients
      with AS. The observation of two skin related malignancies, including one
      melanoma, during the whole study period of 7 years is in line with reports from
      previous large AS data sets.

PMID- 27049734
TI  - Chemical and semisynthetic approaches to study and target deubiquitinases.
AB  - Ubiquitination is a key posttranslational modification, which affects numerous
      biological processes and is reversed by a class of enzymes known as
      deubiquitinases (DUBs). This family of enzymes cleaves mono-ubiquitin or poly
      ubiquitin chains from a target protein through different mechanisms and mode of
      interactions with their substrates. Studying the role of DUBs in health and
      diseases has been a major goal for many laboratories both in academia and in
      industry. However, the field has been challenged by the difficulties in obtaining
      native substrates and novel reagents using traditional enzymatic and molecular
      biology approaches. Recent advancements in the synthesis and semisynthesis of
      proteins made it possible to prepare several unique ubiquitin conjugates to study
      various aspects of DUBs such as their specificities and structures. Moreover,
      these approaches enable the preparation of novel activity based probes and assays
      to monitor DUB activities in vitro and in cellular contexts. Efforts made to
      bring new chemical entities for the selective inhibition of DUBs based on these
      tools are also highlighted with selected examples. 

PMID- 27049735
TI  - Evaluation of staining and color changes of a resin infiltration system.
AB  - OBJECTIVE: To analyze the staining and color changes of a resin infiltrant system
      used for management of white spot lesions (WSLs). MATERIALS AND METHODS: WSLs
      were artificially created on left buccal halves of 48 extracted human teeth.
      These sites were then treated with resin infiltration (RI) while the right halves
      of the teeth remained as nonresin (NRI) areas. Six groups were formed (n = 8
      teeth/group) and were exposed to the following: red wine, coffee, orange juice,
      combined staining agents, accelerated aging, and distilled water for 1 week. The
      teeth were then polished with a prophy cup and polishing paste. Color properties
      were assessed using a spectrophotometer at baseline (T0), after each exposure
      (T1), and after polishing (T2). Color difference (DeltaE*) was calculated between
      each time point for both halves of the teeth (RI and NRI). Data were analyzed
      with a two-way analysis of variance with presence of resin infiltration and
      staining agents as the main effects for each time point pair. Multiple
      comparisons were made with a Bonferroni post hoc test. The level of significance
      was set at P < .05. RESULTS: The red wine and combined staining agent groups
      caused the greatest color change between all intervals (P < .05). Significant
      interactions were recorded between resin infiltration application and staining
      agents at all time periods (P < .05). The presence of resin infiltration as a
      main effect did not affect color change between T0 and T2 (P > .05). CONCLUSIONS:
      RI areas showed higher staining susceptibility than did NRI areas. However,
      prophylaxis had a strong effect on reversing the discoloration of both RI and NRI
      areas.

PMID- 27049736
TI  - Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic
      Anemia.
AB  - BACKGROUND: Clostridium perfringens (C. perfringens) can cause various
      infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C.
      perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin
      of this bacterium induces massive intravascular hemolysis by disrupting red blood
      cell membranes. CASE REPORT: We present the case of a male patient with diabetes
      who developed a fatal liver abscess with massive intravascular hemolysis and
      septic shock caused by toxigenic C. perfringens. The peripheral blood smear
      showed loss of central pallor, with numerous spherocytes. Multiplex PCR only
      detected expression of the cpa gene, indicating that the pathogen was C.
      perfringens type A. CONCLUSIONS: C. perfringens infection should be considered in
      a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed
      blood sample, and negative Coombs test. The characteristic peripheral blood smear
      findings may facilitate rapid diagnosis.

PMID- 27049737
TI  - Fabrication of Isolated Metal-Organic Polyhedra in Confined Cavities:
      Adsorbents/Catalysts with Unusual Dispersity and Activity.
AB  - Metal-organic polyhedra (MOPs) have attracted great attention due to their
      intriguing structure. However, the applications of MOPs are severely hindered by
      two shortcomings, namely low dispersity and poor stability. Here we report the
      introduction of four MOPs (constructed from dicopper and carboxylates) to cavity
      structured mesoporous silica SBA-16 via a double-solvent strategy to overcome
      both shortcomings simultaneously. By judicious design, the dimension of MOPs is
      just between the size of cavities and entrances of SBA-16, MOP molecules are thus
      confined in the cavities. This leads to the formation of isolated MOPs with
      unusual dispersion, making the active sites highly accessible. Hence, the
      adsorption capacity on carbon dioxide and propene as well as catalytic
      performance on ring opening are much superior to bulk MOPs. More importantly, the
      structure and catalytic activity of MOPs in confined cavities are well preserved
      after exposure to humid atmosphere, whereas those of bulk MOPs are degraded
      seriously.

PMID- 27049738
TI  - [On Bian Que and the culture of witch doctor of Eastern Yi Ethnic Group as viewed
      from the Picture of Bian Que's Needling in the stone-carved figure of Han
      Dynasty].
AB  - The culture of witch doctor of the Eastern Ethnic Yi Group exerted profound
      influence on early acupuncture art and medicine. There is a score of Bian Que's
      Needling Picture in the stone-carved figure unearthed in Shandong Province,
      demonstrating the origin of acupuncture in the region of Eastern Yi Ethnic Group.
      Bian Que, with the identity of witch doctor, and"doctor stone needling witch"with
      the legend of a professional acupuncturing indicates the important influence of
      witch doctor on the origin of acupuncture art.The archeological discovery of
      tortoise shell, divination carved on bones, and conical needles all buried
      together in the Da-wen-kou culture indicates that the earliest therapy witch
      doctor applied was related to needling. As a representative of the Eastern Yi
      Ethnic Group, Bian Que,"the Father of Medical Prescription"was the embryonic form
      of early acupuncture art, promoted the formation and development of early medical
      theory, the theory of pulse feeling, being the important part of the early stage
      of origin of needling-pulse feeling theory. 

PMID- 27049739
TI  - [On Annotation on the Names and Syndromes of Ancient Diseases, with textual
      research on"dian (depressive psychosis)","kuang (manic psychosis)", and"xian
      (epilepsy)"].
AB  - The book Gu dai ji bing ming hou shu yi (Annotation on the Names and Syndromes of
      Ancient Diseases) written by Yu Yunxiu holds that dian can be divided into two
      conditions, namely, epilepsy and manic psychosis. By analysis on related
      materials in ancient lexicographical works, ancient medical books and other
      ancient books, it reveals that dian and kuang are two very different diseases,
      but dian and xian refer to the same conditions. Dian was the special name of a
      disease, while xian was a stage of syndrome of that disease with typical
      symptoms. Dian and xian might also refer to two different types of that disease.
      Dian always refers to epilepsy from its very beginning besides cephalopathy,
      including both mental symptom and physical symptom. 

PMID- 27049740
TI  - [The differentiation and vicissitude of variety of Aucklandiae Radix].
AB  - Aucklandiae Radix is a commonly used Chinese herbal medicine. Historically, the
      varieties of Aucklandiae Radix for its medicinal use are complicated. Early Radix
      Aucklandiae was produced domestically, and it began to be imported since the
      Northern and Southern Dynasties. The two families, four genera, including
      Saussure Aucklandiae Radix of Compositae, Inula Inulae Radix, Vladimiria
      Vladimiriae Radix, dali Aucklandiae Radix and Aristolochiaceae Aristolochic
      aristolochia debilis, are all applied for medicinal purposes. In modern time,
      there are 3 major classes of crude drugs of Aucklandiae Radix, namely,
      Aucklandiae Radix, Inulae Radix, root of common Vladimiriae Radix. 

PMID- 27049741
TI  - [On medical risk control in Chinese missionary hospitals in China during 1820
      1860].
AB  - In the missionary hospitals founded in the nineteenth century by the missionaries
      in China, the sprout of consciousness of medical risk control emerged. They did
      their best to avoid medical accidents which might lead to anti-missionary
      struggle by the Chinese people, and were especially cautious to control the
      happening of medical accidents. First of all, the hospitals made careful
      screening on patients by giving priority to those patients pursuing treatment of
      eye diseases, and barely forced to accept patients with intractable and critical
      diseases. Second, before the operation, the missionary doctors usually let the
      patient sign an agreement of consent for surgical operation, with the patient
      him/herself responsible for all the consequences of operation. Generally, the
      patient(s) won't be hospitalized, even though the work of their nursing was
      generally done by the patient's relatives. All these three initiatives promoted
      the spread of western medicine in China and expanded a positive influence of
      western medicine, though it seemed to be contradictory to the principles of
      equality and universal love of Christianity. 

PMID- 27049742
TI  - [The changes of nurse uniform style in Pakhoi Po Yan Hospital in recent hundred
      year].
AB  - Nurse uniforms are the nurse's professional clothing, the main features of which
      are to keep clean and for easy identification. Culture consciousness has been
      added into nurse uniforms by people's behavior during the course of its
      application. Through the investigation on the historical materials of Pakhoi Po
      Yan Hospital (founded by Church Missionary Society in April 1886 in Pakhoi), it
      can be found that the nurse uniforms of different ages reflect the cultural
      background of the changes and the development of nursing career. This not only
      deduces the nurse culture and progress, but also reflects the continuation of
      nursing care, its responsibility and innovation. 

PMID- 27049743
TI  - [On the epidemic of cholera and its prevention and control by the railway
      authorities in 1932].
AB  - In 1932, the epidemic of cholera in China was serious, spreading to all provinces
      nationwide, causing heavy casualties. In order to prevent cholera epidemics
      spread along the railway line, the National Government Ministry of Railways and
      the local railway administration had taken all countermeasures, including the
      promulgation of epidemic prevention laws and regulations, quarantine, isolated
      check-up, disinfection, vaccination and even interruption of traffic. The
      measures of railway authorities had achieved a certain success. In August 1932,
      cholera epidemic began to subside gradually. 

PMID- 27049744
TI  - [A brief history of Beijing Shijitan(Century Altar) Hospital].
AB  - Founded in 1914, the Jing-Han Railway Hospital has undergone through four
      different stages during its 100 years' transition, viz., from 1914 to 1949, from
      1949 to 1979, from 1980 to 2003 and from 2004 to the present, with its title
      changing from Peking-Hankou Railway Hospital, Beijing Health Care Station,
      Peiping Railway Hospital, Beijing Railway General Hospital and today's Beijing
      Shijitan Hospital. As a railway hospital, in addition to offering services to
      Chinese railway health, it has also participated in many public welfare
      activities, such as major disaster rescues, important domestic medical services,
      the international medical assistance, hospitals' counterpart support, Lifeline
      Express and so on.In a sense, the establishment and development of the hospital
      are connected with Beijing Railway Health Services and is not only closely
      related with China's railway healthcare, but also to modern social transformation
      and changes. 

PMID- 27049745
TI  - [Preliminary exploration on the relationship between hand-copied edition and
      block-printed edition of Fu ke cai zhen (Collected Essentials of Women Disease)].
AB  - There are two extant versions of Fu ke cai zhen (Collected Essentials of Women
      Disease) nowadays, namely, Yang Jichun's hand-copied version, and block-printed
      version of Direntang Sanctum. The former one was formally sorted out by Prof.
      Wang Yaoting of the Changchun College of TCM and published in 1988 in the Jilin
      Journal of TCM in serial form. Though Yang's version was completed later than the
      block-printed one, however, it can be found by careful comparison that it was not
      copied after the block-printed edition, but probably written from the draft of
      the author himself. 

PMID- 27049746
TI  - [Random notes on the hygienic works in the guerrilla of eastern Zhejiang Province
      of New Fourth Army].
AB  - Being reorganized on the basis of the 3rd and 5th branches of Songhu Guerrilla
      and its 3rd column, the Eastern Zhejiang Guerrilla got remarkable achievements in
      the health works from nothing. It is especially so and deserved written
      description for the Rear Hospitals of Sanbei when its medical staffs were
      surrounded by the Japanese and Kuomintang troops under very difficult conditions,
      which were overcome by the support of local people. 

PMID- 27049747
TI  - [Practice and inspiration: Schweitzer's road to medicine and his view of life
      ethics].
AB  - Albert Schweitzer established the hospital in the African jungle and practiced
      medicine for over a half of century. He proposed"reverence for life"and became a
      thought and practice unifier. The Schweitzer's Hospital was not only a medical
      institution, but also a social institution for education. Later, the school,
      consulting office and medical institute were also set up in Africa. For over a
      century, the Schweitzer's Hospital always insisted on the ethics of respecting
      individual and reverence for life, which enlightened modern medical practice and
      medical education. The introduction of the ethics of"reverence for life"to
      clinical practice would exert very important effect for establishing the harmony
      and equality of doctor-patient relationship. 

PMID- 27049748
TI  - [The cultural and medical significance of Xin an mingzuzhi(History of Famous
      Family in Xin'an)].
AB  - History of Famous Family in Xin'an includes abundant information and important
      value of the medical cultural history, including the medical family, medical
      ethics and the number of the famous doctors and its distribution, the medical
      books and its outline the medical ethics, the diseases. As for the 115 famous
      doctors recorded in this book, Shexian county owns the most while Jixi county
      owns the least, and of the average number of famous doctors among the 10, 000
      local people, Yixian county owns the most while Xiuning county owns the least.
      History of Famous Family in Xin'an includes 26 medical books, ranging from
      medical literature study, gynecological treatment, external medical treatment,
      diagnosis and treatment of pediatric diseases, ancient medical case records,
      medical education, acu-moxibustion and summary of other medical experiences. The
      book also demonstrates the noble morality of doctors, development of doctor'
      family, and records of paralytic stroke, epistaxis, tuberculous consumptive
      diseases, furunculosis, dystocia and some infectious diseases. 

PMID- 27049749
TI  - Steering microtubule shuttle transport with dynamically controlled magnetic
      fields.
AB  - Nanoscale control of matter is critical to the design of integrated nanosystems.
      Here, we describe a method to dynamically control directionality of microtubule
      (MT) motion using programmable magnetic fields. MTs are combined with magnetic
      quantum dots (i.e., MagDots) that are manipulated by external magnetic fields
      provided by magnetic nanowires. MT shuttles thus undergo both ATP-driven and
      externally-directed motion with a fluorescence component that permits
      simultaneous visualization of shuttle motion. This technology is used to alter
      the trajectory of MTs in motion and to pin MT motion. Such an approach could be
      used to evaluate the MT-kinesin transport system and could serve as the basis for
      improved lab-on-a-chip technologies based on MT transport. 

PMID- 27049750
TI  - Energy Decomposition Analysis with a Stable Charge-Transfer Term for Interpreting
      Intermolecular Interactions.
AB  - Many schemes for decomposing quantum-chemical calculations of intermolecular
      interaction energies into physically meaningful components can be found in the
      literature, but the definition of the charge-transfer (CT) contribution has
      proven particularly vexing to define in a satisfactory way and typically depends
      strongly on the choice of basis set. This is problematic, especially in cases of
      dative bonding and for open-shell complexes involving cation radicals, for which
      one might expect significant CT. Here, we analyze CT interactions predicted by
      several popular energy decomposition analyses and ultimately recommend the
      definition afforded by constrained density functional theory (cDFT), as it is
      scarcely dependent on basis set and provides results that are in accord with
      chemical intuition in simple cases, and in quantitative agreement with
      experimental estimates of the CT energy, where available. For open-shell
      complexes, the cDFT approach affords CT energies that are in line with trends
      expected based on ionization potentials and electron affinities whereas some
      other definitions afford unreasonably large CT energies in large-gap systems,
      which are sometimes artificially offset by underestimation of van der Waals
      interactions by density functional theory. Our recommended energy decomposition
      analysis is a composite approach, in which cDFT is used to define the CT
      component of the interaction energy and symmetry-adapted perturbation theory
      (SAPT) defines the electrostatic, polarization, Pauli repulsion, and van der
      Waals contributions. SAPT/cDFT provides a stable and physically motivated energy
      decomposition that, when combined with a new implementation of open-shell SAPT,
      can be applied to supramolecular complexes involving molecules, ions, and/or
      radicals. 

PMID- 27049751
TI  - The influence of chemical reactivity of surface defects on ambient-stable InSe
      based nanodevices.
AB  - We demonstrate that, in contrast to most two-dimensional materials, ultrathin
      flakes of InSe are stable under ambient conditions. Despite their ambient
      stability, InSe-based nanodevices show an environmental p-type doping, suppressed
      by capping InSe with hexagonal boron nitride. By means of transport experiments,
      density functional theory and vibrational spectroscopy, we attribute the p-type
      doping assumed by uncapped InSe under an ambient atmosphere to the decomposition
      of water at Se vacancies. We have estimated the site-dependent adsorption energy
      of O2, N2, H2O, CO and CO2 on InSe. A stable adsorption is found only for the
      case of H2O, with a charge transfer of only 0.01 electrons per water molecule. 

PMID- 27049752
TI  - Peroxidase-like Catalytic Activity of Copper-Mediated Protein-Inorganic Hybrid
      Nanoflowers and Nanofibers of beta-Lactoglobulin and alpha-Lactalbumin:
      Synthesis, Spectral Characterization, Microscopic Features, and Catalytic
      Activity.
AB  - A free Cys-SH-containing protein, beta-lactoglobulin (beta-LG), and another
      protein not possessing the same, viz., apo-alpha-lactoglobulin (apo-alpha-LA),
      were used in studies to demonstrate the role of this amino acid, along with its
      secondary structure, in the formation of a protein dimer and a protein-inorganic
      hybrid nanoflower and in the creation of the peroxidase-like activity of the
      nanomaterials produced when the proteins were treated with varying Cu(2+)
      concentration under different pH conditions. An increase in the pH as well as the
      Cu(2+) mole ratio results in increasing dimer formation in case of beta-LG due to
      the presence of free Cys121-SH, while the dimer is not formed in case of apo
      alpha-LA under the same conditions. The role of Cys in the dimer formation has
      been demonstrated both by MALDI and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis studies. Both of the proteins exhibited changes in their
      secondary structures to different extents as a function of pH, and the structures
      were stabilized by Cu(2+) interactions, as studied by CD and fluorescence
      spectroscopy. The small and spherical nanoparticles formed at pH 7 with lower
      equivalents of Cu(2+) join together to form larger aggregates at higher
      equivalents of Cu(2+). For the same concentration at pH 9, both the aggregates
      and the nanoflowers were noticed. However, at pH 12, the Cu(2+) binding induces
      the formation of fibers along with the flowers. Both the nanoflowers and
      nanofibers exhibited peroxidase-like activity in a catalytic manner. Nanoflowers
      were also shown to detect phenol in the concentration range from 10 to 200 MUM.
      The copper-induced nanobiomaterial obtained in the case of apo-alpha-LA also
      exhibited peroxidase-like activity. Thus, this paper deals with the green
      synthesis of copper-induced protein (beta-LG/apo-alpha-LA)-inorganic hybrid
      nanomaterials that are important due to their applications as nanobiomaterials.

PMID- 27049753
TI  - Influence of aqueous food simulants on potential nanoparticle detection in
      migration studies involving nanoenabled food-contact substances.
AB  - Research focused on assessing potential consumer exposure to nanoparticles
      released from nano-enabled food-contact materials (FCMs) has often reached
      conflicting conclusions regarding the detection of migrating nanoparticles. These
      conflicting conclusions, coupled with the potential for nanoparticles to be
      unstable in certain food simulants, has necessitated a closer look at the role
      played by food simulants recommended for use in nanoparticle migration
      evaluation. The influence of aqueous food simulants on nanoparticles under
      migration evaluation conditions is reported herein. The stability of silver
      nanoparticles (AgNP) spiked into three food simulants (water, 10% ethanol and 3%
      acetic acid) was investigated using asymmetric flow field-flow fractionation
      (AF4), ultrafiltration, electron microscopy (EM), and single-particle inductively
      coupled plasma mass spectrometry (sp-ICP-MS). While 3% acetic acid induced
      significant oxidative dissolution of AgNP to silver ions, there were very minor
      to no changes in the physicochemical properties of AgNP in water and 10% ethanol.

PMID- 27049754
TI  - Interactive effect of microstructure and cavity dimension on filling behavior in
      micro coining of pure nickel.
AB  - In this study, interactive effects of microstructure and cavity dimension on the
      filling behaviors in micro coining were investigated. The results indicate that
      the filling ability is dependent on both the cavity width t and the ratio of
      cavity width to grain size t/d strongly. The critical ratio t/d for the worst
      filling ability increases with cavity width t and tends to disappear when the
      cavity width t increases to 300 MUm. A polycrystalline filling model considering
      the friction size effect, effect of constrained grains by the tools, grain size,
      cavity width and ratio of cavity width to grain size is proposed to reveal the
      filling size effect in micro coining. A quasi in-situ Electron Backscatter
      Diffraction (EBSD) method is proposed to investigate filling mechanism in micro
      coining. When several grains across the cavity width, each grain deforms
      heterogeneously to ordinate the deformation compatibility. When there is only one
      grain across the cavity width, the grain is fragmented into several smaller
      grains with certain prolongation along the extrusion direction to coordinate the
      deformation in the cavity. This is different from the understandings before. Then
      the filling deformation mechanism is revealed by a proposed model considering the
      plastic flow in micro coining.

PMID- 27049756
TI  - First Ecological Study of the Bawean Warty Pig (Sus blouchi), One of the Rarest
      Pigs on Earth.
AB  - The Bawean warty pig (Sus blouchi) is an endemic pig species confined to the 192
      km(2) large island of Bawean in the Java Sea, Indonesia. Due to a lack of
      quantitative ecological research, understanding of natural history and
      conservation requirements have so far been based solely on anecdotal information
      from interviews with local people and study of captive and museum specimens. In
      this study we provide the first assessment of population and habitat preferences
      for S. blouchi by using camera trapping. From the 4th of November 2014 to January
      8th 2015, we placed camera traps at 100 locations in the forested protected areas
      on Bawean. In 690.31 camera days (16567.45 hours) we captured 92 independent
      videos showing S. blouchi. Variation in S. blouchi trapping rates with cumulative
      trap effort stabilized after 500 camera days. An important outcome is that, in
      contrast to the suggestion of previous assessments, only S. blouchi was detected
      and no S. scrofa was found, which excludes hybridization threats. We fitted a
      Random Encounter Model, which does not require the identification of individual
      animals, to our camera-trapping data and estimated 172-377 individuals to be
      present on the island. Activity patterns and habitat data indicate that S.
      blouchi is mainly nocturnal and prefers community forests and areas near forest
      borders. Next to this, we found a positive relationship between S. blouchi
      occupancy, distance to nearest border, litter depth and tree density in the
      highest ranking occupancy models. Although these relationships proved non
      significant based on model averaging, their presence in the top ranking models
      suggests that these covariables do play a role in predicting S. blouchi
      occurrence on Bawean. The estimated amount of sites occupied reached 58%. Based
      on our results, especially the estimation of the population size and area of
      occupancy, we determine that the species is Endangered according to the IUCN/SSC
      Red List criteria.

PMID- 27049755
TI  - G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion,
      and Metastasis.
AB  - Triple negative breast cancer (TNBC) is a heterogeneous disease that has a poor
      prognosis and limited treatment options. Chemokine receptor interactions are
      important modulators of breast cancer metastasis; however, it is now recognized
      that quantitative surface expression of one important chemokine receptor, CXCR4,
      may not directly correlate with metastasis and that its functional activity in
      breast cancer may better inform tumor pathogenicity. G protein coupled receptor
      kinase 3 (GRK3) is a negative regulator of CXCR4 activity, and we show that GRK
      expression correlates with tumorigenicity, molecular subtype, and metastatic
      potential in human tumor microarray analysis. Using established human breast
      cancer cell lines and an immunocompetent in vivo mouse model, we further
      demonstrate that alterations in GRK3 expression levels in tumor cells directly
      affect migration and invasion in vitro and the establishment of distant
      metastasis in vivo. The effects of GRK3 modulation appear to be specific to
      chemokine-mediated migration behaviors without influencing tumor cell
      proliferation or survival. These data demonstrate that GRK3 dysregulation may
      play an important part in TNBC metastasis. 

PMID- 27049757
TI  - Towards a Better Understanding of the Effects of UV on Atlantic Walruses,
      Odobenus rosmarus rosmarus: A Study Combining Histological Data with Local
      Ecological Knowledge.
AB  - Walruses, Odobenus rosmarus, play a key role in the Arctic ecosystem, including
      northern Indigenous communities, which are reliant upon walruses for aspects of
      their diet and culture. However, walruses face varied environmental threats
      including rising sea-water temperatures and decreasing ice cover. An
      underappreciated threat may be the large amount of solar ultraviolet radiation
      (UV) that continues to reach the Arctic as a result of ozone loss. UV has been
      shown to negatively affect whales. Like whales, walrus skin is unprotected by
      fur, but in contrast, walruses spend long periods of time hauled-out on land. In
      this study, we combined the results of histological analyses of skin sections
      from five Atlantic walruses, Odobenus rosmarus rosmarus, collected in Nunavik
      (Northern Quebec, Canada) with qualitative data obtained through the interviews
      of 33 local walrus hunters and Inuit Elders. Histological analyses allowed us to
      explore UV-induced cellular lesions and interviews with experienced walrus
      hunters and Elders helped us to study the incidences and temporal changes of UV
      induced gross lesions in walruses. At the microscopic scale, we detected a range
      of skin abnormalities consistent with UV damage. However, currently such UV
      effects do not seem to be widely observed at the whole-animal level (i.e.,
      absence of skin blistering, erythema, eye cataract) by individuals interviewed.
      Although walruses may experience skin damage under normal everyday UV exposure,
      the long-term data from local walrus hunters and Inuit Elders did not report a
      relation between the increased sun radiation secondary to ozone loss and walrus
      health. 

PMID- 27049758
TI  - Effect of Polyelectrolyte Stiffness and Solution pH on the Nanostructure of
      Complexes Formed by Cationic Amphiphiles and Negatively Charged Polyelectrolytes.
AB  - The interaction between amphiphiles and polyelectrolytes has been widely
      investigated in recent years due to their potential application in industry and
      medicine, with special focus on gene therapy. The cationic lipid dioleoyl
      trimethylammonium propane, DOTAP, and the oppositely charged polyelectrolytes,
      sodium poly(acrylic acid) and sodium poly(styrenesulfonate), form multilamellar
      complexes in water. Because of the different molecular stiffness of the two
      polyelectrolytes, they form different nanostructured complexes. Also, because of
      the different ionization behavior of the two polyelectrolytes, pH differently
      affects the complexation of the polyelectrolytes with didodecyldimethylammonium
      bromide (DDAB), another cationic surfactant. We used cryogenic temperature
      transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering
      (SAXS) to compare the nanostructures formed. Our results show that although the
      basic nanostructures of the complexes are always lamellar (multilamellar or
      unilamellar) the morphology of the complexes is affected by the polyelectrolyte
      rigidity and the solution pH.

PMID- 27049759
TI  - GSK-3alpha Is a Novel Target of CREB and CREB-GSK-3alpha Signaling Participates
      in Cell Viability in Lung Cancer.
AB  - Overexpression or activation of cyclic AMP-response element-binding protein
      (CREB) has been known to be involved in several human malignancies, including
      lung cancer. Genes regulated by CREB have been reported to suppress apoptosis,
      induce cell proliferation, inflammation, and tumor metastasis. However, the
      critical target genes of CREB in lung cancer have not been well understood. Here,
      we identified GSK-3alpha as one of the CREB target genes which is critical for
      the viability of lung cancer cells. The CREB knockdown significantly reduced the
      expression of GSK-3alpha and the direct binding of CREB on the promoter of GSK3A
      was identified. Kaplan-Meier analysis with a public database showed a prognostic
      significance of aberrant GSK-3alpha expression in lung cancer. Inhibition of GSK
      3alpha suppressed cell viability, colony formation, and tumor growth. For the
      first time, we demonstrated that GSK-3alpha is regulated by CREB in lung cancer
      and is required for the cell viability. These findings implicate CREB-GSK-3alpha
      axis as a novel therapeutic target for lung cancer treatment. 

PMID- 27049760
TI  - Screening Glycolipids Against Proteins in Vitro Using Picodiscs and Catch-and
      Release Electrospray Ionization-Mass Spectrometry.
AB  - This work describes the application of the catch-and-release electrospray
      ionization-mass spectrometry (CaR-ESI-MS) assay, implemented using picodiscs
      (complexes comprised of saposin A and lipids, PDs), to screen mixtures of
      glycolipids (GLs) against water-soluble proteins to detect specific interactions.
      To demonstrate the reliability of the method, seven gangliosides (GM1, GM2, GM3,
      GD1a, GD1b, GD2, and GT1b) were incorporated, either individually or as a
      mixture, into PDs and screened against two lectins: the B subunit homopentamer of
      cholera toxin (CTB5) and a subfragment of toxin A from Clostridium difficile
      (TcdA-A2). The CaR-ESI-MS results revealed that CTB5 binds to six of the
      gangliosides (GM1, GM2, GM3, GD1a, GD1b, and GT1b), while TcdA-A2 binds to five
      of them (GM1, GM2, GM3, GD1a, and GT1b). These findings are consistent with the
      measured binding specificities of these proteins for ganglioside
      oligosaccharides. Screening mixtures of lipids extracted from porcine brain and a
      human epithelial cell line against CTB5 revealed binding to multiple GM1 isoforms
      as well as to fucosyl-GM1, which is a known ligand. Finally, a comparison of the
      present results with data obtained with the CaR-ESI-MS assay implemented using
      nanodiscs (NDs) revealed that the PDs exhibited similar or superior performance
      to NDs for protein-GL binding measurements.

PMID- 27049761
TI  - Allospecific Tregs Expanded After Anergization Remain Suppressive in Inflammatory
      Conditions but Lack Expression of Gut-homing Molecules.
AB  - Cell therapy with antigen-specific regulatory T-cells (Treg) has great potential
      to selectively control unwanted immune responses after allogeneic stem-cell or
      solid organ transplantation and in autoimmune diseases. Ex vivo allostimulation
      with costimulatory blockade (alloanergization) of human T-cells expands
      populations of alloantigen-specific Treg, providing a cellular strategy to
      control donor T-cell alloresponses causing graft-versus-host disease after
      allogeneic hematopoietic stem-cell transplantation. Crucially, it is not known if
      Treg expanded in this way are stable in proinflammatory conditions encountered
      after transplantation, or if they possess capacity to migrate to key target
      organs. Using an in vitro model to functionally characterize human Treg expanded
      after alloanergization, we now show that these cells remain potently
      allosuppressive in the presence of relevant exogenous inflammatory signals.
      Expanded allospecific Treg retained expression of molecules conferring migratory
      capacity to several organs but small intestine-specific chemotaxis was markedly
      impaired, in keeping with the preponderance of gut graft-versus-host disease in
      previous clinical studies using this strategy. Importantly, impaired gut-specific
      chemotaxis could be partially corrected by pharmacological treatment. These
      findings will facilitate more effective application of this cellular approach to
      limit T-cell alloresponses after hematopoietic stem-cell transplantation and the
      wider application of the strategy to other clinical settings.

PMID- 27049762
TI  - Deubiquitinase Ubp5 Is Required for the Growth and Pathogenicity of Cryptococcus
      gattii.
AB  - Cryptococcus gattii is a resurgent fungal pathogen that primarily infects
      immunocompetent hosts. Thus, it poses an increasingly significant impact on
      global public health; however, the mechanisms underlying its pathogenesis remain
      largely unknown. We conducted a detailed characterization of the deubiquitinase
      Ubp5 in the biology and virulence of C. gattii using the hypervirulent strain
      R265, and defined its properties as either distinctive or shared with C.
      neoformans. Deletion of the C. gattii Ubp5 protein by site-directed disruption
      resulted in a severe growth defect under both normal and stressful conditions
      (such as high temperature, high salt, cell wall damaging agents, and antifungal
      agents), similar to the effects observed in C. neoformans. However, unlike C.
      neoformans, the C. gattii ubp5Delta mutant displayed a slight enhancement of
      capsule and melanin production, indicating the evolutionary convergence and
      divergence of Ubp5 between these two sibling species. Attenuated virulence of the
      Cg-ubp5Delta mutant was not solely due to its reduced thermotolerance at 37
      degrees C, as shown in both worm and mouse survival assays. In addition, the
      assessment of fungal burden in mammalian organs further indicated that Ubp5 was
      required for C. gattii pulmonary survival and, consequently, extrapulmonary
      dissemination. Taken together, our work highlights the importance of
      deubiquitinase Ubp5 in the virulence composite of both pathogenic cryptococcal
      species, and it facilitates a better understanding of C. gattii virulence
      mechanisms. 

PMID- 27049763
TI  - Trophic Niche Differentiation in Rodents and Marsupials Revealed by Stable
      Isotopes.
AB  - Tropical rainforests support the greatest diversity of small mammals in the
      world, yet we have little understanding about the mechanisms that promote the
      coexistence of species. Diet partitioning can favor coexistence by lessening
      competition, and interspecific differences in body size and habitat use are
      usually proposed to be associated with trophic divergence. However, the use of
      classic dietary methods (e.g. stomach contents) is challenging in small mammals,
      particularly in community-level studies, thus we used stable isotopes (delta13C
      and delta15N) to infer about trophic niche. We investigated i) how trophic niche
      is partitioned among rodent and marsupial species in three Atlantic forest sites
      and ii) if interspecific body size and locomotor habit inequalities can
      constitute mechanisms underlying the isotopic niche partitioning. We found that
      rodents occupied a broad isotopic niche space with species distributed in
      different trophic levels and relying on diverse basal carbon sources (C3 and C4
      plants). Surprisingly, on the other hand, marsupials showed a narrow isotopic
      niche, both in delta13C and delta15N dimensions, which is partially overlapped
      with rodents, contradicting their description as omnivores and generalists
      proposed classic dietary studies. Although body mass differences did not
      explained the divergence in isotopic values among species, groups of species with
      different locomotor habit presented clear differences in the position of the
      isotopic niche space, indicating that the use of different forest strata can
      favor trophic niche partitioning in small mammals communities. We suggest that
      anthropogenic impacts, such as habitat modification (logging, harvesting), can
      simplify the vertical structure of ecosystems and collapse the diversity of basal
      resources, which might affect negatively small mammals communities in Atlantic
      forests. 

PMID- 27049764
TI  - Bioactive non-sterol triterpenoid from Streblus asper: microwave-assisted
      extraction, HPTLC profiling, computational studies and neuro-pharmacological
      evaluation in BALB/c mice.
AB  - CONTEXT: In folk medicine, the stem bark of Streblus asper Lour. (Moraceae) has
      been reported to possess anticonvulsant activity. However, no
      systematic/scientific validation is available. Objective This study explores the
      constituents in the stem bark, their biosassy-guided isolation and their efficacy
      in neuro-pharmacological disorders, for validating the traditional claims.
      MATERIALS AND METHODS: Microwave-assisted extraction (MAE) technique was employed
      to obtain the crude extract. The n-hexane, dichloromethane and aqueous fractions
      were prepared and phytoconstituents were ascertained by phytochemical tests. The
      isolated compound, betulin, was characterized by different physicochemical and
      spectral methods, including HPTLC. Finally, neuro-pharmacological evaluations
      were conducted at 100, 200, 400 mg/kg b.w., p.o. (25, 50, 100 mg/kg b.w. for
      betulin) doses in BALB/c mice. RESULTS: The n-hexane fraction (400 mg/kg), and
      isolated compound betulin (100 mg/kg), showed maximum anticonvulsant activity in
      maximal electroshock (87.84% and 85.14% seizure inhibition), and isoniazid
      induced convulsion models (88.85% and 83.18% seizure inhibition), respectively. A
      dose-dependent attenuation of epileptic seizures was observed, probably through
      GABArgic mechanism of anticonvulsant action. Moreover, the antidepressant study
      was also conducted using behavioural models and the results expound that n-hexane
      and dichloromethane fractions (400 mg/kg) significantly reduced the duration of
      immobility, as compared to the control. DISCUSSION AND CONCLUSION: This study
      reports some novel aspects like applying an environmentally benign/green approach
      of MAE, neuro-pharmacological screening and use of docking studies, for the first
      time, on the plant S. asper. The findings present a rational explanation for its
      use in traditional medicine, for the management of neuro-pharmacological
      disorders.

PMID- 27049766
TI  - Diagnostic Accuracy of Procalcitonin and C-reactive Protein for the Early
      Diagnosis of Intra-abdominal Infection After Elective Colorectal Surgery: A Meta
      analysis.
AB  - OBJECTIVE: Intra-abdominal infections (IAIs) after elective colorectal surgery
      impact significantly the short- and long-term outcomes. In the era of fast-track
      surgery, they often come to light after discharge from hospital. Early diagnosis
      is therefore essential. C-reactive protein levels have proved to be accurate in
      this setting. Procalcitonin has been evaluated in several studies with
      conflicting results. This meta-analysis aimed to compare the predictive abilities
      of C-reactive protein and procalcitonin in the occurrence of IAIs after elective
      colorectal surgery. METHODS: This meta-analysis included studies analyzing C
      reactive protein and/or procalcitonin levels at postoperative days 2, 3, 4,
      and/or 5 as markers of intra-abdominal infection after elective colorectal
      surgery. Methodological quality was assessed by the QUADAS2 tool. The area under
      the curve summary receiver-operating characteristic was calculated for each day
      and each biomarker, using a random-effects model in cases of heterogeneity.
      RESULTS: The meta-analysis included 11 studies (2692 patients). An IAI occurred
      in 8.9% of the patients. On postoperative day 3, area under the curve was 0.80
      (95% CI, 0.76-0.85) for C-reactive protein and 0.78 (95% CI, 0.68-0.87) for
      procalcitonin. On postoperative day 5, their predictive accuracies were 0.87 (95%
      CI, 0.80-0.93) and 0.90 (95% CI, 0.82-0.98), respectively. The accuracy of C
      reactive protein and procalcitonin did not differ at any postoperative day.
      CONCLUSIONS: Levels of inflammatory markers under the cutoff value between
      postoperative days 3 and 5 ensure safe early discharge after elective colorectal
      surgery. Procalcitonin seems not to have added value as compared to C-reactive
      protein in this setting.

PMID- 27049765
TI  - Brain Cortical Thickness Differences in Adolescent Females with Substance Use
      Disorders.
AB  - METHODS: We recruited right-handed female patients, 14-19 years of age, from a
      university-based treatment program for youths with substance use disorders and
      community controls similar for age, race and zip code of residence. We obtained
      43 T1-weighted structural brain images (22 patients and 21 controls) to examine
      group differences in cortical thickness across the entire brain as well as six a
      priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior
      cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ
      were entered as nuisance factors for all analyses. RESULTS: A priori region-of
      interest analyses yielded no significant differences. However, whole-brain group
      comparisons revealed that the left pregenual rostral anterior cingulate cortex
      extending into the left medial orbitofrontal region (355.84 mm2 in size), a
      subset of two of our a priori regions-of-interest, was significantly thinner in
      patients compared to controls (vertex-level threshold p = 0.005 and cluster-level
      family wise error corrected threshold p = 0.05). The whole-brain group
      differences did not survive after adjusting for depression or externalizing
      scores. Whole-brain within-patient analyses demonstrated a positive association
      between cortical thickness in the left precuneus and behavioral disinhibition
      scores (458.23 mm2 in size). CONCLUSIONS: Adolescent females with substance use
      disorders have significant differences in brain cortical thickness in regions
      engaged by the default mode network and that have been associated with problems
      of emotional dysregulation, inhibition, and behavioral control in past studies.

PMID- 27049767
TI  - Intention-to-treat Analysis Controls the Bias When Suffer From Noncompliance and
      Missing Outcomes in Randomized Controlled Trial Study.

PMID- 27049768
TI  - Safety of Continued Clopidogrel Use in the Preoperative Course of
      Gastrointestinal Surgery: A Retrospective Cohort Study.
AB  - OBJECTIVE: Our study aimed to estimate postoperative bleeding risk in older
      adults taking clopidogrel before gastrointestinal (GI) surgery, to aid surgeons
      in decisions regarding clopigogrel cessation. SUMMARY BACKGROUND DATA: Balancing
      risks of postoperative bleeding associated with continued clopidogrel use and
      those associated with cessation is difficult for GI surgeons. METHODS: Using 100%
      Texas Medicare Claims Data from 2006 to 2011, we identified patients undergoing
      emergent GI surgery. We propensity score matched patients on clopidogrel before
      surgery to patients not on clopidogrel. Using conditional logistic regression, we
      compared risks of bleeding events at 1-month postdischarge between groups,
      adjusting for bleeding risk factors. RESULTS: In total, 1240 patients undergoing
      emergent GI surgery while treated with clopidogrel were matched to emergency GI
      surgery patients not treated with clopidogrel. The only significant preoperative
      differences between groups were higher percent of clopidogrel-treated patients
      with congestive heart failure, cholecystectomy, and lower percent of clopidogrel
      treated patients with colectomy. Mean age was 76.91 (+/-7.06) and 76.70 (+/-7.05)
      years (P = 0.47), and 63.84% and 59.41% of operations were cholecystectomy, in
      the clopidogrel and nonclopidogrel groups (P = 0.18). In multivariable analyses
      adjusting for Elixhauser index, hyperlipidemia, confounding drugs, and surgery
      type, odds ratio for bleeding within 30 days of discharge in those exposed to
      clopidogrel compared with those not exposed was 1.60 (95% confidence interval,
      1.08-2.38), with raw rates of bleeding 6.85% and 4.84%. CONCLUSIONS: Clopidogrel
      use in older adults through the preoperative period of GI surgery does not
      significantly increase bleeding events in the month after surgery.

PMID- 27049769
TI  - Attention and working memory training: A feasibility study in children with
      neurodevelopmental disorders.
AB  - The current study investigated the efficacy of a game-based process specific
      intervention for improving attention and working memory in children with Fetal
      Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD). The
      Caribbean Quest (CQ) is a 'serious game' that consists of five hierarchically
      structured tasks, delivered in an adaptive format, targeting different aspects of
      attention and/or working memory. In addition to game play, the intervention
      incorporates metacognitive strategies provided by trained educational assistants
      (EAs), to facilitate generalization and far transfer to academic and daily
      skills. EAs delivered the intervention to children (ages 6-13) during their
      regular school day, providing children with instruction in metacognitive
      strategies to improve game play, with participants completing approximately 12
      hours of training over an 8 to 12 school week period. Pre- and post-test analyses
      revealed significant improvement on measures of working memory and attention,
      including reduced distractibility and improved divided attention skills.
      Additionally, children showed significant gains in performance on an academic
      measure of reading fluency, suggesting that training-related gains in attention
      and working memory transferred to classroom performance. Exit interviews with EAs
      revealed that the intervention was easily delivered within the school day, that
      children enjoyed the intervention, and that children transferred metacognitive
      strategies learned in game play into the classroom. Preliminary results support
      this game-based process specific intervention as a potentially effective
      treatment and useful tool for supporting cognitive improvements in children with
      FASD or ASD, when delivered as part of an overall treatment plan.

PMID- 27049770
TI  - Corrigendum.

PMID- 27049772
TI  - Non-singular terminal dynamic surface control based integrated guidance and
      control design and simulation.
AB  - In this paper, a novel cascade type design model is transformed from the
      simulation model, which has a broader scope of application, for integrated
      guidance and control (IGC). A novel non-singular terminal dynamic surface control
      based IGC method is proposed. It can guarantee the missile with multiple
      disturbances fast hits the target with high accuracy, while considering the
      terminal impact angular constraint commendably. And the stability of the closed
      loop system is strictly proved. The essence of integrated guidance and control
      design philosophy is reached that establishing a direct relation between guidance
      and attitude equations by "intermediate states" and then designing an IGC law for
      the obtained integrated cascade design model. Finally, a series of simulations
      and comparisons with a 6-DOF nonlinear missile that includes all aerodynamic
      effects are demonstrated to illustrate the effectiveness and advantage of the
      proposed IGC method. 

PMID- 27049771
TI  - Cache Domains That are Homologous to, but Different from PAS Domains Comprise the
      Largest Superfamily of Extracellular Sensors in Prokaryotes.
AB  - Cellular receptors usually contain a designated sensory domain that recognizes
      the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of
      species ranging from bacteria to humans. Although PAS domains were described as
      intracellular sensors, recent structural studies revealed PAS-like domains in
      extracytoplasmic regions in several transmembrane receptors. However, these
      structurally defined extracellular PAS-like domains do not match sequence-derived
      PAS domain models, and thus their distribution across the genomic landscape
      remains largely unknown. Here we show that structurally defined extracellular PAS
      like domains belong to the Cache superfamily, which is homologous to, but
      distinct from the PAS superfamily. Our newly built computational models enabled
      identification of Cache domains in tens of thousands of signal transduction
      proteins including those from important pathogens and model organisms.
      Furthermore, we show that Cache domains comprise the dominant mode of
      extracellular sensing in prokaryotes. 

PMID- 27049773
TI  - The Functional IgE-Blocking Factor Induced by Allergen-Specific Immunotherapy
      Correlates with IgG4 Antibodies and a Decrease of Symptoms in House Dust Mite
      Allergic Children.
AB  - BACKGROUND: At present, there are no validated biomarkers reflecting or
      predicting the clinical efficacy of allergen-specific immunotherapy (AIT) . We
      aimed to investigate the correlations between clinical and immunological
      responses of patients undergoing house dust mite (HDM) AIT. METHODS: Sixty-nine
      children diagnosed with HDM allergic rhinitis and/or asthma received standardized
      Dermatophagoides pteronyssinus (Dp) subcutaneous AIT for 12 months. Twenty HDM
      allergic children served as an open control group. Clinical symptom and
      medication scores were recorded and Dp-specific IgE, IgG4 and IgE-blocking factor
      were measured before AIT and after 4 and 12 months of AIT. RESULTS: Symptom
      scores decreased after 4 months and continued to decrease during 12 months of
      AIT. No differences in medication scores were observed between AIT and the
      control group during the study period. Levels of Dp IgG4 increased after 4 months
      and correlated to symptom scores at 12 months (r = -0.296, p = 0.013) of AIT. The
      Dp IgE-blocking factor increased after 4 months of AIT, and correlated with
      symptom scores at 4 months (r = -0.307, p = 0.010) and 12 months (r = -0.288, p =
      0.016) of AIT. A strong correlation between Dp IgE-blocking factor and Dp IgG4
      during AIT (4 months: r = 0.680; 12 months: r = 0.636, both p < 0.0001) was
      observed. Patients with IgE-blocking factor >=0.2 after 4 months of AIT showed
      lower symptom scores at 12 months of AIT (p = 0.0093). CONCLUSIONS: Subcutaneous
      HDM AIT results in a decrease of allergic symptoms among HDM-allergic children.
      IgE-blocking activity increased after 4 months of AIT and correlated with
      clinical symptoms. A high IgE-blocking factor at an early stage of AIT is
      associated with fewer symptoms at a later stage of AIT.

PMID- 27049774
TI  - Prevention of Cognitive Decline: A Physical Exercise Perspective on Brain Health
      in the Long Run.

PMID- 27049775
TI  - Timely Diagnosis for Dementia: The Need for Specialists.

PMID- 27049776
TI  - Myosonographic study of abdominal wall dynamics to assess donor site morbidity
      after microsurgical breast reconstruction with a DIEP or an ms-2 TRAM flap.
AB  - BACKGROUND: Currently, autologous breast reconstruction with a free tissue
      transfer from the lower abdomen is considered to be a safe method that provides a
      stable long-term solution. The DIEP-flap and the ms-2-TRAM-flap reconstructions
      have helped reduce donor site morbidity. In order to assess the potential
      differences between these techniques, we carried out myosonographic evaluations
      that assessed the muscle dynamics pre- and post-operatively. In addition to
      investigating the properties of the rectus abdominis muscle post-operatively,
      this prospective study also allowed us to analyse the muscle preoperatively and
      to investigate the prospects for harvesting a DIEP-flap as opposed to a TRAM
      flap. MATERIALS AND METHODS: Sixty patients underwent breast reconstruction with
      71 (11 bilateral) free abdominal wall flaps (DIEP-: n = 48; ms-2-TRAM-flap: n =
      23). Myosonographic examinations were performed preoperatively and at 3 and 6
      months post-operatively. The thickness of the muscle at relaxation and maximum
      contraction and the difference between the muscle thickness measured at the two
      states were measured. A general-linear-model (GLM) was used for statistical
      analysis. The main variable was the surgical method, and the co-variables
      included BMI and patient age. The decision on whether to harvest a DIEP- or ms-2
      TRAM-flap was made intra-operatively and based on the dominant perforator.
      RESULTS: It shows that the patients who underwent breast reconstruction with a
      DIEP-flap had significantly better muscle function (p < 0.05) in the follow-up.
      In addition, the analysis revealed that better muscle function before surgery
      made it more likely that a patient would undergo a DIEP-flap-reconstruction
      successfully. Patient age also had a highly significant effect on muscle recovery
      (p < 0.0005). CONCLUSIONS: This prospective study used a dynamic ultrasound
      evaluation of the abdominal wall and showed that the DIEP-flap significantly
      reduces donor site morbidity compared to the ms-2-TRAM-flap. The study also
      showed that good preoperative muscle function might increase the probability of
      surgeons performing a DIEP-flap reconstruction.

PMID- 27049777
TI  - Dissection of Levels II Through V Is Required for Optimal Outcomes in Patients
      with Lateral Neck Lymph Node Metastasis from Papillary Thyroid Carcinoma.
AB  - BACKGROUND: Completeness of surgical resection is an important determinant of
      outcomes in patients with papillary thyroid carcinoma and regional lymph node
      metastasis. The extent of therapeutic lateral neck dissection remains
      controversial. This study aims to assess the impact of modified radical neck
      dissection of levels II to V in a large patient series. STUDY DESIGN:
      Retrospective analysis of consecutive patients with papillary thyroid carcinoma
      who underwent lateral neck dissection at a single institution from June 1, 2006
      to December 31, 2014 was performed. RESULTS: A total of 241 lateral neck
      dissections were performed in 191 patients (118 [62%] women; median age 46 years
      [range 6 to 87 years]; median follow-up 14.3 months [range 0.1 to 107 months]).
      Overall, 202 initial neck dissections (195 modified radical neck dissections and
      7 less extensive dissections) were performed. Among these initial dissections,
      137 (68.8%), 132 (65.7%), 105 (52.0%), and 33 (16.9%) had positive lymph nodes in
      levels II, III, IV, and V, respectively. Ipsilateral lymph node persistence or
      recurrence occurred after 22 (10.9%) initial dissections, at level II in 10
      (45.5%), level III in 8 (36.4%), level IV in 7 (31.8%), and level V in 3 (13.6%).
      Thirty-nine reoperative lateral neck dissection were performed, including 18
      cases of persistence and recurrence after our initial dissections. In reoperative
      dissections, positive lymph nodes were confirmed in levels II, III, IV, and V in
      18 (46.2%), 10 (25.6%), 13 (33.3%), and 5 (12.8%) dissections, respectively.
      Temporary nerve injury occurred in 6 (3.0%) initial and 4 (10.3%) reoperative
      dissections, respectively. There were no permanent nerve injuries. CONCLUSIONS:
      Omitting levels II and V during lateral neck dissection for papillary thyroid
      carcinoma potentially misses level II disease in two-thirds of patients and level
      V disease in one-fifth of patients. Formal modified radical neck dissection is
      necessary to avoid the morbidity of reoperative surgery.

PMID- 27049778
TI  - Pilot Randomized Controlled Trial of Laparoscopic Cholecystectomy vs Active
      Nonoperative Therapy for the Treatment of Biliary Dyskinesia.
AB  - BACKGROUND: Despite widespread adoption by the surgical community, high-quality
      prospective data supporting the practice of laparoscopic cholecystectomy (LC) for
      the treatment of biliary dyskinesia (BD) are lacking. STUDY DESIGN: Adult
      patients meeting criteria for diagnosis of BD (Rome III symptoms, normal
      ultrasound, gallbladder ejection fraction < 38%) were randomized to either LC or
      a trial of nonoperative (NO) therapy with a low-dose neuromodulator
      (amitriptyline 25 mg/day). Patients in the NO arm were allowed to cross over to
      the surgical arm and remain in the study for any reason. Besides collection of
      basic demographics and medical/surgical history, patients were administered a
      standardized quality of life (QOL) assessment (Short Form-8) and a symptom
      specific questionnaire (Rome III criteria) at enrollment and monthly through the
      study to assess the effect of treatment on biliary symptoms and overall QOL.
      RESULTS: Thirty patients were enrolled over 12 months (15 LC, 15 NO). In the LC
      group, 13 underwent LC, 1 refused surgery, 1 withdrew. In the NO group, 14
      crossed over to the LC group (13 of whom had LC), yielding 26 patients who
      underwent LC. The SF-8 physical scores (PCS-8) were significantly improved at
      both the first and last follow-up visits (p < 0.0001, p = 0.0003, respectively).
      The SF-8 mental scores (MCS-8) were also significantly improved at both the first
      and last follow-up visits (p = 0.0187, p = 0.0017, respectively). With median
      follow-up of 12 months (range 3 to 14 months), all 26 reported relief of pain.
      CONCLUSIONS: This pilot study raises doubts regarding the feasibility of a
      randomized trial, presumably due to both clinician and patient bias toward LC and
      the lack of "gold-standard" nonoperative treatments. However, these prospective
      data indicate that, with careful patient selection (standardized symptom
      criteria/imaging methodology), LC results in pain relief and significant
      improvement in QOL in BD patients. Further prospective study of these findings is
      warranted.

PMID- 27049779
TI  - Inpatient Rehabilitation after Liver Transplantation Decreases Risk and Severity
      of 30-Day Readmissions.
AB  - BACKGROUND: Discharge location is associated with short-term readmission rates
      after hospitalization for several medical and surgical diagnoses. We hypothesized
      that discharge location: home, home health, skilled nursing facility (SNF), long
      term acute care (LTAC), or inpatient rehabilitation, independently predicted the
      risk of 30-day readmission and severity of first readmission after orthotopic
      liver transplantation. STUDY DESIGN: We performed a retrospective cohort review
      using Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases
      for Florida and California. Patients who underwent orthotopic liver
      transplantation from 2009 to 2011 were included and followed for 1 year. Mixed
      effects logistic regression was used to model the effect of discharge location on
      30-day readmission controlling for demographic, socioeconomic, and clinical
      factors. Total cost of first readmission was used as a surrogate measure for
      readmission severity and resource use. RESULTS: A total of 3,072 patients met our
      inclusion criteria. The overall 30-day readmission rate was 29.6%. Discharge to
      inpatient rehabilitation (adjusted odds ratio [aOR] 0.43, p = 0.013) or LTAC/SNF
      (aOR 0.63, p = 0.014) were associated with decreased odds of 30-day readmission
      when compared with home. The severity of 30-day readmissions for patients
      discharged to inpatient rehabilitation were the same as those discharged home or
      home with home health. Severity was increased for those discharged to LTAC/SNF.
      The time to first readmission was longest for patients discharged to inpatient
      rehabilitation (17 days vs 8 days, p < 0.001). CONCLUSIONS: When compared with
      other locations of discharge, inpatient rehabilitation reduces the risk of 30-day
      readmission and increases the time to first readmission. These benefits come
      without increasing the severity of readmission. Increased use of inpatient
      rehabilitation after orthotopic liver transplantation is a strategy to improve 30
      day readmission rates.

PMID- 27049780
TI  - Benefits of Multimodal Enhanced Recovery Pathway in Patients Undergoing Open
      Ventral Hernia Repair.
AB  - BACKGROUND: Use of Enhanced Recovery After Surgery (ERAS) pathways have evidenced
      improved outcomes in several surgical specialties. The effectiveness of ERAS
      pathways specific to hernia surgery, however, has not yet been investigated. We
      hypothesized that our ERAS pathway would accelerate functional recovery and
      shorten hospitalization in patients undergoing open ventral hernia repair (VHR).
      STUDY DESIGN: Consecutive patients undergoing open major VHR using transversus
      abdominis release and sublay synthetic mesh placement, with use of our ERAS
      pathway, were compared with a historical cohort before ERAS implementation. Main
      outcomes measures were time to diet advancement, time to return of bowel
      function, time to oral narcotics, length of stay (LOS), and 90-day readmissions.
      RESULTS: Between January 2014 and January 2015, 100 patients undergoing VHR with
      ERAS implementation were compared with a historical cohort. The ERAS group
      demonstrated significantly shorter times to liquid and regular diet: 1.1 vs 2.7
      and 3.0 vs 4.8 days, respectively (p < 0.001). Furthermore, ERAS patients
      demonstrated significantly shorter times to flatus and bowel movement: 3.1 vs 3.9
      and 3.6 vs 5.2 days, respectively (p < 0.001). Average LOS was reduced from 6.1
      to 4.0 days (p < 0.001), and ERAS patients had significantly fewer 90-day
      readmissions, 4% vs 16% (p < 0.001). CONCLUSIONS: A comprehensive ERAS pathway
      for major open VHR was implemented safely. Multimodal perioperative pain
      management, oral opioid-receptor blockade, and early feeding strategies resulted
      in accelerated intestinal recovery, shorter hospitalizations, and fewer
      readmissions. Use of our ERAS pathway appears to result in improved outcomes in
      patients undergoing open VHR.

PMID- 27049781
TI  - Implementation of the Surgical Safety Checklist in South Carolina Hospitals Is
      Associated with Improvement in Perceived Perioperative Safety.
AB  - BACKGROUND: Previous research suggests that surgical safety checklists (SSCs) are
      associated with reductions in postoperative morbidity and mortality as well as
      improvement in teamwork and communication. These findings stem from evaluations
      of individual or small groups of hospitals. Studies with more hospitals have
      assessed the relationship of checklists with teamwork at a single point in time.
      The objective of this study was to evaluate the impact of a large-scale
      implementation of SSCs on staff perceptions of perioperative safety in the
      operating room. STUDY DESIGN: As part of the Safe Surgery 2015 initiative to
      implement SSCs in South Carolina hospitals, we administered a validated survey
      designed to measure perception of multiple dimensions of perioperative safety
      among clinical operating room personnel before and after implementation of an
      SSC. RESULTS: Thirteen hospitals administered baseline and follow-up surveys,
      separated by 1 to 2 years. Response rates were 48.4% at baseline (929 of 1,921)
      and 42.7% (815 of 1,909) at follow-up. Results suggest improvement in all of the
      5 dimensions of teamwork (relative percent improvement ranged from +2.9% for
      coordination to +11.9% for communication). These were significant after adjusting
      for respondent characteristics, hospital fixed-effects, multiple comparisons, and
      clustering robust standard errors by hospital (all p < 0.05). More than half of
      respondents (54.1%) said their surgical teams always used checklists effectively;
      73.6% said checklists had averted problems or complications. CONCLUSIONS: A large
      scale initiative to implement SSCs is associated with improved staff perceptions
      of mutual respect, clinical leadership, assertiveness on behalf of safety, team
      coordination and communication, safe practice, and perceived checklist outcomes.

PMID- 27049782
TI  - Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection
      in Nonmetastatic Breast Cancer Patients.
AB  - BACKGROUND: Circulating tumor cells (CTCs) can be identified in approximately 25%
      of nonmetastatic breast cancer patients, and data are emerging regarding their
      prognostic significance. We hypothesized that CTCs identified before resection of
      the primary tumor would predict worse outcomes in nonmetastatic breast cancer
      patients. STUDY DESIGN: We performed CTC enumerations on 509 patients with
      nonmetastatic breast cancer as part of an IRB-approved study. The CTCs (per 7.5
      mL blood) were identified using the CellSearch System (Janssen). The presence of
      >=1 CTC meeting morphologic criteria for malignancy was considered a positive
      result. Log-rank test and Cox regression analysis were applied to establish the
      association of CTCs with relapse-free and overall survival. RESULTS: Median
      follow-up was 48 months and mean age was 53 years. Fifty-nine percent of patients
      (299 of 509) had tumors larger than 2 cm, and 46% (234 of 509) had positive lymph
      nodes. One hundred sixty-six patients received neoadjuvant chemotherapy (NACT)
      before CTC assessment, and 343 patients were chemonaive. One or more CTC was
      identified in 43 of 166 (26%) NACT treated patients, and in 81 of 343 (24%)
      chemonaive patients. Circulating tumor cells were not associated with tumor size,
      grade, or lymph node status (p = NS). Detection of 1 or more CTCs predicted
      decreased relapse-free (log-rank p < 0.001, hazard ratio [HR] 2.72, 95% CI 1.57
      to 4.72; p < 0.001) and overall survival (log-rank p = 0.02, HR 2.29, 95% CI 1.12
      to 4.67; p = 0.03) at 48 months of follow-up. CONCLUSIONS: One or more CTCs
      identified before resection of the primary breast tumor predicted worse relapse
      free and overall survival, irrespective of primary tumor size, grade, or lymph
      node positivity.

PMID- 27049783
TI  - Optimal Perioperative Management of the Geriatric Patient: A Best Practices
      Guideline from the American College of Surgeons NSQIP and the American Geriatrics
      Society.

PMID- 27049784
TI  - Preoperative Cholangitis and Future Liver Remnant Volume Determine the Risk of
      Liver Failure in Patients Undergoing Resection for Hilar Cholangiocarcinoma.
AB  - BACKGROUND: The highest mortality rates after liver surgery are reported in
      patients who undergo resection for hilar cholangiocarcinoma (HCCA). In these
      patients, postoperative death usually follows the development of hepatic
      insufficiency. We sought to determine the factors associated with postoperative
      hepatic insufficiency and death due to liver failure in patients undergoing
      hepatectomy for HCCA. STUDY DESIGN: This study included all consecutive patients
      who underwent hepatectomy with curative intent for HCCA at 2 centers, from 1996
      through 2013. Preoperative clinical and operative data were analyzed to identify
      independent determinants of hepatic insufficiency and liver failure-related
      death. RESULTS: The study included 133 patients with right or left major (n = 67)
      or extended (n = 66) hepatectomy. Preoperative biliary drainage was performed in
      98 patients and was complicated by cholangitis in 40 cases. In all these
      patients, cholangitis was controlled before surgery. Major (Dindo III to IV)
      postoperative complications occurred in 73 patients (55%), with 29 suffering from
      hepatic insufficiency. Fifteen patients (11%) died within 90 days after surgery,
      10 of them from liver failure. On multivariate analysis, predictors of
      postoperative hepatic insufficiency (all p < 0.05) were preoperative cholangitis
      (odds ratio [OR] 3.2), future liver remnant (FLR) volume < 30% (OR 3.5),
      preoperative total bilirubin level >3 mg/dL (OR 4), and albumin level < 3.5 mg/dL
      (OR 3.3). Only preoperative cholangitis (OR 7.5, p = 0.016) and FLR volume < 30%
      (OR 7.2, p = 0.019) predicted postoperative liver failure-related death.
      CONCLUSIONS: Preoperative cholangitis and insufficient FLR volume are major
      determinants of hepatic insufficiency and postoperative liver failure-related
      death. Given the association between biliary drainage and cholangitis, the
      preoperative approach to patients with HCCA should be optimized to minimize the
      risk of cholangitis.

PMID- 27049785
TI  - Uncertain Patency of Covered Stents Placed for Traumatic Axillosubclavian Artery
      Injury.
AB  - BACKGROUND: Traumatic axillosubclavian artery injuries (ASAIs) are uncommon but
      devastating. There is increasing acceptance of covered stent use for ASAIs.
      However, epidemiologic and long-term outcomes data are limited. We investigated
      national trends in ASAI management and our institutional outcomes after emergent
      covered stent placement and open surgical repairs for ASAIs. STUDY DESIGN: A
      review of the National Trauma Data Bank from 2010 to 2012 was performed for
      epidemiologic data. International Classification of Diseases and procedure codes
      were used to identify ASAIs and therapy type. A single-center, retrospective
      review of consecutive patients with ASAIs between January 2010 and August 2014
      was also performed. RESULTS: National Trauma Data Bank review included 511,286
      patients with 520 ASAIs, yielding an incidence of 0.1%. Endovascular therapy was
      used in 76 patients (14.7%) vs open repair in 280 patients (53.8%). Nonoperative
      or unknown treatment was used in 164 (31.5%). From 2010 to 2012, endovascular
      interventions increased from 11.3% to 17.2% (p < 0.05). Endovascular therapy was
      used more frequently in blunt compared with penetrating trauma (59.2% vs 40.8%; p
      < 0.005). Our institutional review identified 10 ASAIs treated with covered
      stents with a median follow-up of 117 days (interquartile range 13 to 447 days)
      and 70% lost to follow-up. No treatment-related mortality or amputation occurred.
      Stent occlusion occurred in 30% at a median of 132 days (interquartile range 30
      to 223 days). Three patients with ASAIs were initially treated with open surgery,
      2 died and the third required ligation. CONCLUSIONS: Covered stents are being
      used increasingly for ASAIs nationwide, despite variable reports of durability.
      Follow-up is poor in urban trauma centers and might be responsible for the
      variable patency. Population-based efforts to improve compliance among trauma
      patients can help improve covered stent patency in ASAI.

PMID- 27049786
TI  - Carbohydrate Antigen 19-9 Elevation in Anatomically Resectable, Early Stage
      Pancreatic Cancer Is Independently Associated with Decreased Overall Survival and
      an Indication for Neoadjuvant Therapy: A National Cancer Database Study.
AB  - BACKGROUND: Patient triage in anatomically resectable, early stage pancreatic
      ductal adenocarcinoma (PDAC) with elevated carbohydrate antigen 19-9 (CA 19-9)
      remains unclear. We hypothesized that any CA 19-9 elevation indicates
      biologically borderline resectability. STUDY DESIGN: The National Cancer Data
      Base (NCDB 2010 to 2012) was reviewed for PDAC patients with reported CA 19-9.
      Nonsecretors were analyzed separately. Early stage (I/II) patients were
      stratified by CA 19-9 above or below normal (37 U/mL). Unadjusted Kaplan-Meier
      and adjusted Cox proportional hazards survival modeling were performed. RESULTS:
      Of 113,145 patients, only 28,074 (24.8%) had CA 19-9 measured and reported, and
      this proportion was stage independent. Among early stage patients (n = 10,806),
      there were 957 (8.8%) nonsecretors, 2,708 (25.1%) with normal levels, and 7,141
      (66.1%) with elevated levels. Demographics and perioperative outcomes were
      similar between these groups. Survival was worse in all stages in patients with
      CA 19-9 elevation. Nonsecretors had survival similar to that of patients with
      normal levels. Early stage patients with elevated CA 19-9 had decreased survival
      at 1, 2, and 3 years (56% vs 68%, 30% vs 42%, 15% vs 25%, all p < 0.001) relative
      to patients with normal levels. Adjusted modeling confirmed this finding (hazard
      ratio [HR] 1.26, p < 0.001). Repeat modeling in the neoadjuvant cohort
      demonstrated this to be the only treatment sequence to completely abrogate
      increased mortality due to CA 19-9 elevation (p = 0.11). CONCLUSIONS: The
      minority of PDAC patients have CA 19-9 measured and reported in NCDB. The CA 19-9
      nonsecretors and normal-level patients achieve equivalent survival. Elevation of
      CA 19-9 is associated with decreased stage-specific survival, with the greatest
      difference in early stages. Neoadjuvant systemic therapy followed by curative
      intent surgery best mitigates the increased mortality hazard. Patients with PDAC
      who have elevated CA 19-9 levels at diagnosis are biologically borderline
      resectable regardless of anatomic resectability, and neoadjuvant systemic therapy
      is suggested.

PMID- 27049787
TI  - Unmasking silent neurotoxicity following developmental exposure to environmental
      toxicants.
AB  - Silent neurotoxicity, a term introduced approximately 25years ago, is defined as
      a persistent change to the nervous system that does not manifest as overt
      evidence of toxicity (i.e. it remains clinically unapparent) unless unmasked by
      experimental or natural processes. Silent neurotoxicants can be challenging for
      risk assessors, as the multifactorial experiments needed to reveal their effects
      are seldom conducted, and they are not addressed by current study design
      guidelines. This topic was the focus of a symposium addressing the interpretation
      and use of silent neurotoxicity data in human health risk assessments of
      environmental toxicants at the annual meeting of the Developmental
      Neurotoxicology Society (previously the Neurobehavioral Teratology Society) on
      June 30th, 2014. Several factors important to the design and interpretation of
      studies assessing the potential for silent neurotoxicity were discussed by the
      panelists and audience members. Silent neurotoxicity was demonstrated to be
      highly specific to the characteristics of the animals being examined, the
      unmasking agent tested, and the behavioral endpoint(s) evaluated. Overall, the
      experimental examples presented highlighted a need to consider common adverse
      outcomes and common biological targets for chemical and non-chemical stressors,
      particularly when the exposure and stressors are known to co-occur. Risk
      assessors could improve the evaluation of silent neurotoxicants in assessments
      through specific steps from researchers, including experiments to reveal the
      molecular targets and mechanisms that may result in specific types of silent
      neurotoxicity, and experiments with complex challenges reminiscent of the human
      situation.

PMID- 27049789
TI  - Effects of soil properties on the uptake of pharmaceuticals into earthworms.
AB  - Pharmaceuticals can enter the soil environment when animal slurries and sewage
      sludge are applied to land as a fertiliser or during irrigation with contaminated
      water. These pharmaceuticals may then be taken up by soil organisms possibly
      resulting in toxic effects and/or exposure of organisms higher up the food chain.
      This study investigated the influence of soil properties on the uptake and
      depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and
      orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of
      pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited
      the highest pore water based bioconcentration factors (BCFs) and displayed the
      largest differences between soil types with BCFs ranging between 30.5 and 115.9.
      For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0
      and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in
      certain treatments the presence of these chemicals in the soil matrices changed
      the soil pH over time, with a statistically significant pH difference to control
      samples. The internal pH of E. fetida also changed as a result of incubation in
      pharmaceutically spiked soil, in comparison to the control earthworms. These
      results demonstrate that a combination of soil properties and pharmaceutical
      physico-chemical properties are important in terms of predicting pharmaceutical
      uptake in terrestrial systems and that pharmaceuticals can modify soil and
      internal earthworm chemistry which may hold wider implications for risk
      assessment. 

PMID- 27049790
TI  - Use of sunlight to degrade oxytetracycline in marine aquaculture's waters.
AB  - Oxytracycline (OTC) is a broad spectrum antibiotic authorized for use in European
      aquaculture. Its photo-degradation has been widely studied in synthetic aqueous
      solutions, sometimes resorting to expensive methods and without proven
      effectiveness in natural waters. Thus, this work studied the possibility to apply
      the solar photo-degradation for removal of OTC from marine aquaculture's waters.
      For that, water samples were collected at different locals of the water treatment
      circuit, from two different aquaculture companies. Water samples were firstly
      characterized regarding to pH, salinity, total suspended solids (TSS), organic
      carbon and UV-Vis spectroscopic characteristics. Then, the samples were spiked
      with OTC and irradiated using simulated sunlight in order to evaluate the matrix
      effects on OTC photo-degradation. From kinetic results, the apparent quantum
      yields and the outdoor half-life times, at 40 degrees N for midsummer and
      midwinter days were estimated by the first time for these conditions. For a
      midsummer day, at sea level, the outdoor half-life time predicted for OTC in
      these aquaculture's waters ranged between 21 and 25 min. Additionally, the pH and
      salinity effects on the OTC photo-degradation were evaluated and it has been
      shown that high pH values and the presence of sea salt increase the OTC photo
      degradation rate in aquaculture's waters, compared to results in deionised water.
      The results are very promising to apply this low-cost methodology using the
      natural sunlight in aquaculture's waters to remove OTC. 

PMID- 27049792
TI  - Renal denervation for human hypertension: is there a future?
AB  - The sympathetic nervous system plays a permissive, if not primary causal role in
      the genesis and maintenance of human essential hypertension. Excessive
      sympathetic nervous system activity in man is most apparent in early forms of
      hypertension (prehypertension and white-coat type). Renal nerves are of
      particular interest because of their roles in modulating the activity of the
      renin-angiotensin system and renal sodium excretion. Renal denervation
      substantially ameliorates the development of hypertension in animal models such
      as renovascular, spontaneously hypertensive, and steroid-induced hypertension in
      rats and aortic coarctation in dogs. In man, catheter ablation of renal nerves
      has been undertaken in the late phases of hypertension; in a rigorously
      controlled trial in resistant hypertension (SYMPLICITY HTN-3), renal denervation
      did not reduce blood pressure over the long term. Is this because renal
      denervation is more appropriate to prevent than treat late-stage hypertension?
      Are there anatomical or technical barriers yet to be overcome in the procedure?
      These and other issues are addressed by two experts in this issue of the
      controversies series: Deepak L. Bhatt and Murray Epstein.

PMID- 27049791
TI  - Trophic transfer and effects of DDT in male hornyhead turbot (Pleuronichthys
      verticalis) from Palos Verdes Superfund site, CA (USA) and comparisons to field
      monitoring.
AB  - High concentrations of DDT and metabolites (SigmaDDT) have been detected in
      sediment and the demersal flatfish hornyhead turbot (Pleuronichtys verticalis)
      collected from Palos Verdes (PV), California, USA, a site contaminated with over
      100 metric tons of DDT throughout 1960s-70s. This study was conducted to assess
      the transfer of SigmaDDT from PV-sediment into polychaetes (Neanthes
      arenaceodentata) and hornyhead turbot, and to investigate if the responses in
      turbots from two different laboratory exposures mimic those in turbots caught in
      PV (PV-turbot). Turbot fed PV-sediment-contaminated polychaete for 7 days had
      liver concentrations of SigmaDDT similar to PV-turbot. After 28 days, SigmaDDT
      also accumulated in livers of turbot gavaged with a SigmaDDT mixture. In vitro
      cell bioassays indicated significant increases of 17beta-estradiol equivalents
      (EEQ) in turbot bile extracts as compared to the control in the 7-day study.
      These responses corresponded to those measured in PV-fish. Glucocorticoid
      receptor (GR), anti-androgen receptor (anti-AR), estrogen receptor (ER) or aryl
      hydrocarbon receptor (AhR) activities were also observed in extracts of PV
      sediment, and PV-sediment-exposed worm. Anti-AR, AhR and GR activities were
      significantly higher in PV-sediment than reference sediment (San Diego, SD).
      Higher transcripts of hepatic VTG, ERalpha and ERbeta were found in PV-turbot
      than SD-turbot, but were unaltered in fish exposed to sediment-contaminated worms
      for the 7-day study. In contrast, liver extracts from the 28-day treatment of
      SigmaDDT showed lower EEQ but similar hepatic VTG and ERbeta transcripts relative
      to those of PV-turbot. These data indicated that trophic transfer of sediment
      associated DDT in 7-day exposures corresponded to field measurements of DDT
      residues and in vitro ER bioactivities, but failed to mimic in vivo biological
      effects observed in field fish. In contrast, treatment with SigmaDDT alone for 28
      days mimicked in vivo biological effects of DDTs in PV fish, but did not
      correspond to liver concentrations or in vitro bioactivities. 

PMID- 27049793
TI  - Arginine Patch Predicts the RNA Annealing Activity of Hfq from Gram-Negative and
      Gram-Positive Bacteria.
AB  - The Sm-protein Hfq facilitates interactions between small non-coding RNA (sRNA)
      and target mRNAs. In enteric Gram-negative bacteria, Hfq is required for sRNA
      regulation, and hfq deletion results in stress intolerance and reduced virulence.
      By contrast, the role of Hfq in Gram-positive is less established and varies
      among species. The RNA binding and RNA annealing activity of Hfq from Escherichia
      coli, Pseudomonas aeruginosa, Listeria monocytogenes, Bacillus subtilis, and
      Staphylococcus aureus were compared using minimal RNAs and fluorescence
      spectroscopy. The results show that RNA annealing activity increases with the
      number of arginines in a semi-conserved patch on the rim of the Hfq hexamer and
      correlates with the previously reported requirement for Hfq in sRNA regulation.
      Thus, the amino acid sequence of the arginine patch can predict the chaperone
      function of Hfq in sRNA regulation in different organisms.

PMID- 27049794
TI  - Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate
      sodium and naproxen sodium on proteasome activity in cardiac cells.
AB  - The use of nonsteroidal anti-inflammatory drugs (NSAIDs) like meclofenamate
      sodium (MS), used to reduce pain, has been associated with an increased risk of
      cardiovascular disease (CVD). Naproxen (NAP), another NSAID, is not associated
      with increased risk of CVD. The molecular mechanism(s) by which NSAIDs induce CVD
      is unknown. We investigated the effects of MS and NAP on protein homeostasis and
      cardiotoxicity in rat cardiac H9c2 cells and murine neonatal cardiomyocytes. MS,
      but not NAP, significantly inhibited proteasome activity and reduced cardiac cell
      viability at pharmacological levels found in humans. Although proteasome subunit
      gene and protein expression were unaffected by NSAIDs, MS treated cell lysates
      showed higher 20S proteasome content, while purified proteasomes from MS treated
      cells had lower proteasome activity and higher levels of oxidized subunits than
      proteasomes from control cells. Addition of exogenous proteasome to MS treated
      cells improved cell viability. Both MS and NAP increased ROS production, but the
      rate of ROS production was greater in MS than in NAP treated cells. The ROS
      production is likely from mitochondria, as MS inhibited mitochondrial Complexes I
      and III, major sources of ROS, while NAP inhibited Complex I. MS also impaired
      mitochondrial membrane potential while NAP did not. Antioxidants were able to
      prevent the reduced cell viability caused by MS treatment. These results suggest
      that NSAIDs induce cardiotoxicity by a ROS dependent mechanism involving
      mitochondrial and proteasome dysfunction and may explain why some NSAIDs should
      not be given to patients for long periods.

PMID- 27049795
TI  - Epipericardial fat necrosis clinically mimicking pulmonary embolism: computed
      tomographic angiography findings.

PMID- 27049796
TI  - Survival following extreme carboxyhemoglobin elevation.

PMID- 27049797
TI  - Multiantigenic subunitary vaccines against tuberculosis in clinical trials: Where
      do we stand and where do we need to go?
AB  - The idea of presenting this commentary is to bring attention to the current
      status of clinical tests from several multiantigen vaccine candidates based on
      proteins produced by means of genetic engineering and molecular biology
      approaches and to suggest how new emerging technologies (OMICs) and
      bioinformatics might benefit vaccine development for better control of
      tuberculosis.

PMID- 27049798
TI  - Twelve tips for developing and maintaining a remediation program in medical
      education.
AB  - Remediation in medical education, the process of facilitating corrections for
      physician trainees who are not on course to competence, predictably consumes
      significant institutional resources. Although remediation is a logical
      consequence of mandating, measuring, and reporting clinical competence, many
      program leaders continue to take an unstructured approach toward organizing
      effective, efficient plans for struggling trainees, almost all of who will become
      practicing physicians. The following 12 tips derive from a decade of remediation
      experience at each of the authors' three institutions. It is informed by the
      input of a group of 34 interdisciplinary North American experts assembled to
      contribute two books on the subject. We intend this summary to guide program
      leaders to build better remediation systems and emphasize that developing such
      systems is an important step toward enabling the transition from time-based to
      competency-based medical education. 

PMID- 27049808
TI  - Extended versus superextended lymph-node dissection in radical cystectomy:
      subgroup analysis of possible recurrence-free survival benefit.
AB  - Objective The aim of this study was to assess potential benefits of different
      extended lymph-node dissection templates at the time of radical cystectomy as
      treatment for invasive bladder cancer. Materials and methods Between 2004 and
      2012, 578 patients underwent radical cystectomy with lymph-node dissection
      without prior radiotherapy or chemotherapy. Two different historical cohorts were
      constructed: 262 patients underwent intended superextended lymph-node dissection
      (seLND) from January 2004 to January 2009 and 316 patients underwent intended
      extended lymph-node dissection (eLND) from February 2009 to December 2012.
      Recurrence-free survival (RFS) was analysed as the primary outcome. Median follow
      up was 93 (63-123) months and 38 (16-63) months in the two groups, respectively.
      Results There was no significant difference in RFS in the two cohorts (p = 0.87).
      When analysed according to lymph-node status (N0 or N+), there was no significant
      difference in RFS between the two cohorts in the two subgroups (p = 0.41 and p =
      0.48, respectively). When analysed according to tumour stage, patients with non
      organ-confined disease revealed a tendency towards better RFS in the seLND cohort
      (p = 0.14). This tendency was most clearly seen in the subgroup of T3-4 patients
      without lymph-node metastases (N0) (p = 0.14). Conclusions Extending LND up to
      the inferior mesenteric artery (seLND) does not seem to be beneficial to the
      overall population of patients with invasive bladder cancer compared to
      performing an eLND to the aortic bifurcation only. However, a subgroup of
      patients with non-organ-confined disease without macrometastases may benefit from
      seLND. 

PMID- 27049809
TI  - The Effect of Topical Diquafosol Tetrasodium 3% on Dry Eye After Cataract
      Surgery.
AB  - PURPOSE: To evaluate the effectiveness of 3% diquafosol tetrasodium for treating
      dry eye after cataract surgery. METHODS: Among patients who underwent bilateral
      cataract surgery, 34, who met the diagnostic criteria for dry eye syndrome 1 week
      postoperatively, were enrolled. Patients were randomly assigned to receive 3.0%
      diquafosol tetrasodium ophthalmic solution in one eye and 0.9% saline in the
      other eye four times daily for 8 weeks. Dry eye severity was measured at 1, 5,
      and 9 postoperative weeks using the Schirmer 1 test (SIT), tear film breakup time
      (TBUT), and fluorescein corneal staining. tear meniscus height (TMH), tear
      meniscus depth (TMD), and tear meniscus area (TMA) measured using Fourier-domain
      optical coherence tomography and symptom questionnaire scores. RESULTS: TBUT and
      corneal staining significantly improved 8 weeks postoperatively in eyes treated
      with 3.0% diquafosol tetrasodium (p < 0.01, p < 0.01) and were better than normal
      saline-treated eyes (p < 0.01, p < 0.01). SIT did not improve (p = 0.26). TMH,
      TMD, and TMA did not improve at 4 and 8 weeks. All symptom questionnaire scores
      improved in eyes treated with 3.0% diquafosol tetrasodium (all p < 0.01).
      CONCLUSION: The 3.0% diquafosol tetrasodium treatment improved tear film
      stability and subjective symptoms of dry eye after cataract surgery. Increased
      mucin production as a result of diquafosol treatment may have caused these
      results.

PMID- 27049810
TI  - The relationship between knowledge of pain neurophysiology and fear avoidance in
      people with chronic pain: A point in time, observational study.
AB  - Chronic pain is prevalent in the western world; however fear of pain often has a
      greater impact than the degree of initial injury. The aim of this study was to
      explore the relationship between knowledge of the neurophysiology of pain and
      fear avoidance in individuals diagnosed with chronic pain. Twenty-nine people
      with chronic musculoskeletal pain were recruited and completed questionnaires to
      determine their understanding of pain neurophysiology and the degree of their
      fear avoidance beliefs. There was an inverse relationship between knowledge of
      pain neurophysiology and the level of fear avoidance. Patients with higher pain
      knowledge reported less fear avoidance and lower perceived disability due to
      pain. There was no relationship with the educational level or compensable status
      for either variable. The findings suggest that fear avoidance is positively
      influenced by neurophysiology of pain education, so that a higher level of pain
      knowledge is associated with less activity-related fear. The clinical implication
      is that reducing fear avoidance/kinesiophobia using neurophysiology of pain
      education in people with chronic pain may provide an effective strategy to help
      manage fear avoidance and related disability in the chronic pain population in
      order to improve treatment outcomes. 

PMID- 27049811
TI  - Exploratory Approaches for Studying Social Interactions, Dynamics, and
      Multivariate Processes in Psychological Science.
AB  - In this article, I argue for the need of more use of exploratory techniques to
      identify dynamics in social interactions. I describe several approaches as they
      are applied to multivariate time series data. The first approach is an algorithm
      that searches for periods of variability and stability at the individual level as
      well as for patterns of overlap in such periods between the two individuals in a
      couple. These patterns describe the daily ups and downs in the couples' affect
      and are predictive of the state of the couples 1 to 2 years later. The second
      approach, hierarchical segmentation, is based on the idea of partitioning the
      time series in segments with distinct data patterns. In the case of data from
      dyads, as in the illustration, the patterns can be compared in terms of coherence
      between the 2 individuals in the dyad. The third approach is based on network
      analysis, and its use is shown as a method to examine data transitions at the
      individual and dyadic level as well as system-wide coherence in multivariate
      systems. For each approach, I provide examples of its use with empirical data.
      The article ends with general guidelines and recommendations for researchers
      interested in using exploratory methods as a way to examine psychological
      processes. 

PMID- 27049812
TI  - Effects of a Bioavailable Arabinoxylan-enriched White Bread Flour on Postprandial
      Glucose Response in Normoglycemic Subjects.
AB  - The beneficial effects of soluble fibers on carbohydrate metabolism are well
      documented. In this regard, we tested an arabinoxylan-enriched white bread flour,
      obtained by a patented process by which the bran extracted from the milling
      process is enzymatically hydrolyzed in order to separate the soluble fraction
      fiber from the insoluble fiber. We recruited 24 healthy normoglycemic volunteers
      [Age 34-61 +/- 12.5 y; Body Mass Index (BMI) 22.1 +/- 2.5 kg/m(2); Waist
      circumference (WC) 84.43 +/- 8.0 cm; Fat Mass (FM) 22.7 +/- 8.0%] attending the
      Dietetics Outpatient Clinic of the Internal Medicine Department at IRCCS
      Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy. Subjects
      acutely consumed arabinoxylan-enriched white bread (weight: 100 g) or
      isoenergetic control breads, in a double-blind crossover study design. Plasma
      glucose levels were measured just before bread administration and 30 minutes
      afterwards. The 30-minute peak postprandial glucose concentrations after
      arabinoxylan-enriched meals were significantly lower than after the control meal
      (107+/-4.6 mg/dL vs. 121 +/- 5.2 mg/dL; p < 0.05). The here-reported results show
      how postprandial glucose responses were improved by ingestion of the arabinoxylan
      enriched meal. Further studies are needed to clarify whether daily consumption of
      arabinoxylan-enriched bread will benefit patients with type 2 diabetes mellitus. 

PMID- 27049813
TI  - Mid-upper arm circumference v. weight-for-height Z-score for predicting mortality
      in hospitalized children under 5 years of age.
AB  - OBJECTIVE: To compare the performance of mid-upper arm circumference (MUAC)
      against weight-for-height Z-score (WHZ) for predicting inpatient deaths in
      children under 5 years of age. DESIGN: Diagnostic test accuracy study. SETTING:
      Paediatric emergency department of a tertiary care hospital catering to semi
      urban and rural population in Delhi, India. SUBJECTS: Hospitalized children (n
      1663) aged 6 months to 5 years, for whom discharge outcome was available, were
      consecutively recruited over 14 months. MUAC (cm), weight (kg) height (cm),
      clinical details and the outcome were recorded. MUAC (index test) was compared
      with WHZ based on the WHO growth standards (reference test) for predicting the
      outcome. RESULTS: One hundred and twenty-four (7 %) children died during hospital
      stay. Both MUAC < 11.5 cm (adjusted OR (95 % CI): 3.7 (2.43, 5.60), P<0.001) and
      WHZ<-3 (2.0 (1.37, 2.99), P<0.001) served as independent predictors of inpatient
      mortality. However, MUAC was a significantly better predictor of mortality
      compared with WHZ in terms of area under the receiver-operating characteristic
      curve (MUAC=0.698, WHZ=0.541, P<0.001). MUAC<11.5 cm had the best trade-off of
      sensitivity and specificity for predicting inpatient mortality. A combination of
      WHZ<-3 and/or MUAC<11.5 cm did not significantly improve the predictive value
      over that of MUAC/WHZ, assessed individually. CONCLUSION: MUAC<11.5 cm is a
      better predictor of mortality in hospitalized under-5 children, as compared with
      WHZ<-3. It should be measured in all emergency settings to identify the children
      at higher risk of death.

PMID- 27049814
TI  - Typologies of psychiatric admissions and length of inpatient stay in Italy.
AB  - OBJECTIVE: To describe admissions to an inpatient psychiatric unit in Italy over
      a two-year period and explore the influence of demographics, clinical variables
      and organisational and context-related factors on length of stay. METHODS: Data
      were obtained from clinical records and recorded by a psychiatrist through a
      proper checklist. RESULTS: Shorter admissions involved patients with personality
      disorders and substance use disorders. Greater illness severity and difficulties
      in setting a post-discharge programme were associated with longer admissions.
      CONCLUSIONS: Clinical, organisational and context-related factors all had
      significant effects on length of stay.

PMID- 27049815
TI  - Low-frequency ultrasound for drug delivery in the gastrointestinal tract.

PMID- 27049816
TI  - Falling for the dark side of transcription: Nab2 fosters RNA polymerase III
      transcription.
AB  - RNA polymerase III (RNAPIII) synthesizes diverse, small, non-coding RNAs with
      many important roles in the cellular metabolism. One of the open questions of
      RNAPIII transcription is whether and how additional factors are involved.
      Recently, Nab2 was identified as the first messenger ribonucleoprotein particle
      (mRNP) biogenesis factor with a function in RNAPIII transcription.

PMID- 27049817
TI  - 4D MR imaging using robust internal respiratory signal.
AB  - The purpose of this study is to investigate the feasibility of using internal
      respiratory (IR) surrogates to sort four-dimensional (4D) magnetic resonance (MR)
      images. The 4D MR images were constructed by acquiring fast 2D cine MR images
      sequentially, with each slice scanned for more than one breathing cycle. The 4D
      volume was then sorted retrospectively using the IR signal. In this study, we
      propose to use multiple low-frequency components in the Fourier space as well as
      the anterior body boundary as potential IR surrogates. From these potential IR
      surrogates, we used a clustering algorithm to identify those that best
      represented the respiratory pattern to derive the IR signal. A study with healthy
      volunteers was performed to assess the feasibility of the proposed IR signal. We
      compared this proposed IR signal with the respiratory signal obtained using
      respiratory bellows. Overall, 99% of the IR signals matched the bellows signals.
      The average difference between the end inspiration times in the IR signal and
      bellows signal was 0.18 s in this cohort of matching signals. For the acquired
      images corresponding to the other 1% of non-matching signal pairs, the
      respiratory motion shown in the images was coherent with the respiratory phases
      determined by the IR signal, but not the bellows signal. This suggested that the
      IR signal determined by the proposed method could potentially correct the faulty
      bellows signal. The sorted 4D images showed minimal mismatched artefacts and
      potential clinical applicability. The proposed IR signal therefore provides a
      feasible alternative to effectively sort MR images in 4D.

PMID- 27049818
TI  - Age, Obesity, Sarcopenia, and Proximity to Death Explain Reduced Mean Muscle
      Attenuation in Patients with Advanced Cancer.
AB  - BACKGROUND: Cancer cachexia is characterized by skeletal muscle loss. A feature
      of muscle wasting, reduction in the mean muscle attenuation from computed
      tomography images is believed to reflect pathological infiltration of fat into
      muscle. It is a reported prognostic indicator in cancer patients. OBJECTIVES: To
      develop an explanatory multivariate model of muscle attenuation of cancer
      patients incorporating age, sex, disease characteristics, body composition. Time
      to death <=92 days was included in the model as the demarcation of end-stage
      disease. DESIGN: Multivariate general linear model regression analysis of total
      mean muscle attenuation and change in muscle attenuation. SETTING: Regional
      cancer center (Alberta, Canada). PARTICIPANTS: Patients with gastrointestinal and
      respiratory tract cancers (mean age 64+/-11 years, 44% female). MEASUREMENTS:
      Total adipose tissue and skeletal muscle cross sectional area, and mean muscle
      attenuation at the 3rd lumbar vertebra were assessed from baseline computed
      tomography (n=1719), and a subset with repeated measures (n=246 patients with a
      total of 871 images). RESULTS: At baseline, muscle attenuation associated with
      total skeletal muscle (beta 0.09; 95% CI 0.07 to 0.11; p<0.001) and adipose
      tissue (beta -0.032; 95% CI -0.035 to -0.029; p<0.001) cross sectional areas, age
      (beta -0.28; 95% CI -0.32 to -0.24; p<0.001), time to death <=92 days (beta -1.9;
      95% CI -3.1 to -0.7; p=0.003) and male sex (beta -2.3; 95% CI -3.5 to -1.1;
      p<0.001). Change in muscle attenuation over time associated with total adipose
      tissue cross sectional area (beta -0.008; 95% CI -0.012 to -0.004; p<0.001) and
      time to death <=92 days (beta -1.6; 95% CI -3.0 to -0.2; p=0.03). CONCLUSIONS:
      The radiation attenuation of skeletal muscle is lowest in individuals who are
      older, less muscular, have a higher fat mass and are within 92 days of death. Men
      had lower muscle attenuation than women when controlled for other variables.

PMID- 27049819
TI  - Alcohol Use and Frailty in Community-Dwelling Older Persons Aged 65 to 70 Years.
AB  - BACKGROUND: Alcohol use has beneficial as well as adverse consequences on health,
      but few studies examined its role in the development of age-related frailty.
      OBJECTIVES: To describe the cross-sectional and longitudinal association between
      alcohol intake and frailty in older persons. DESIGN: The Lausanne cohort 65+
      population-based study, launched in 2004. SETTING: Community. PARTICIPANTS: One
      thousand five hundred sixty-four persons aged 65-70 years. MEASUREMENTS: Annual
      data collection included demographics, health and functional status, extended by
      a physical examination every 3 years. Alcohol use (AUDIT-C), and Fried's frailty
      criteria were measured at baseline and 3-year follow-up. Participants were
      categorized into robust (0 frailty criterion) and vulnerable (1+ criteria).
      RESULTS: Few participants (13.0%) reported no alcohol consumption over the past
      year, 57.8% were light-to-moderate drinkers, while 29.3% drank above recommended
      thresholds (18.7% "at risk" and 10.5% "heavy" drinkers). At baseline,
      vulnerability was most frequent in non-drinkers (43.0%), least frequent in light
      to-moderate drinkers (26.2%), and amounted to 31.9% in "heavy" drinkers showing a
      reverse J-curve pattern. In multivariate analysis, compared to light-to-moderate
      drinkers, non-drinkers had twice higher odds of prevalent (adjOR: 2.24;
      95%CI:1.39-3.59; p=.001), as well as 3-year incident vulnerability (adjOR: 2.00;
      95%CI:1.02-3.91; p=.043). No significant association was observed among "at risk"
      and "heavy" drinkers. CONCLUSION: Non-drinkers had two-times higher odds of
      prevalent and 3-year incident vulnerability, even after adjusting for their
      baseline poorer health status. Although residual confounding is still possible,
      these results likely reflect a healthy survival effect among drinkers while those
      who experienced health- or alcohol-related problems stopped drinking earlier.

PMID- 27049820
TI  - Grip Strength and Gait Speed of Older Women Receiving Physical Therapy in a Home
      Care Setting.
AB  - Grip strength and gait speed have both been recommended as "vital signs" for
      older adults. I, therefore, sought to determine the extent to which grip strength
      and comfortable gait speed were limited and related in a sample of older women
      home-care patients. A retrospective analysis was conducted using archived initial
      therapy records of 33 older women (mean age = 80.7 years) residing in their homes
      in New England (USA). Demographics, bilateral grip strength and usual gait speed
      data were extracted from the records. Best grip strength was 80.1% of its
      reference norm. Usual gait speed was 38.4% of its reference norm. Significantly
      more patients were below reference norm for gait speed. Both measures were
      significantly less than functional standards as well. The measures were not
      correlated significantly. Grip strength and gait speed are sensitive to
      limitations in older women home-care patients, but not equally so. 

PMID- 27049821
TI  - Reasoning about Frailty in Neurology: Neurobiological Correlates and Clinical
      Perspectives.
AB  - To date, the frailty syndrome has surprisingly attracted limited attention in the
      field of neurology and neuroscience. Nevertheless, several concepts closely
      related to frailty, such as vulnerability, susceptibility, and homeostatic
      reserves, have been increasingly investigated and documented at level of neuronal
      cells, brain networks, and functions. Similarly, several aspects commonly
      assessed in the neurological practice, including cognitive functioning and
      emotional/affective status, clearly appear to be major determinants of the
      individual's vulnerability and resiliency to stressors. Therefore, they should be
      carefully considered in the clinical approach to frail subjects. Moreover,
      dysfunctions of these domains, if timely detected, may be suitable to be targeted
      by interventions providing beneficial effects to the overall health status of the
      individual. In the present article, we discuss the neurobiological processes
      potentially contributing to frailty. Moreover, we reason about the clinical
      manifestations allowing the prompt and easy recognition of frail persons in the
      neurological practice. 

PMID- 27049822
TI  - The Role the Frailty Syndrome Can Play in Advocacy and Resource Allocation for
      Our Ageing Population - Findings in a Dublin Day Hospital.
AB  - Frail individuals are at higher risk of adverse outcomes, and need identification
      and priority access to Comprehensive Geriatric Assessment (CGA). We prospectively
      collected data on new referrals to our day hospital. Levels of frailty were
      measured with the SHARE Frailty Instrument for Primary Care (SHARE-FI). Of 257
      patients assessed (90 men, 167 women), 110 (43%) were non-frail, 66 (26%) pre
      frail and 81 (32%) frail. Mean age was 82 years for the non-frail, 83 for the pre
      frail and 84 for the frail. Forty-one percent of the frail reported two or more
      falls in the preceding year, compared to 38% of the pre-frail and 21% of the non
      frail (P for trend = 0.003). Of 27 patients who were referred for ongoing
      multidisciplinary assessment and rehabilitation, 16 (59%) were frail. The frailty
      syndrome has the potential to become an advocacy tool for older people and help
      target effective, but finite, CGA resources. 

PMID- 27049823
TI  - A General Decline in Cerebrospinal Fluid Flow: An Overlooked Risk Factor for
      Glaucoma?

PMID- 27049824
TI  - A General Decline in Cerebrospinal Fluid Flow: An Overlooked Risk Factor for
      Glaucoma?: Response.

PMID- 27049825
TI  - Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by
      regulating the AMPK-PGC1alpha-SIRT3 signaling pathway.
AB  - Oxidative stress plays a key role in the pathogenesis of diabetic myopathy.
      Celastrol provides a wide range of health benefits, including antioxidant, anti
      inflammatory and antitumor effects. We hypothesized that celastrol may exert an
      antioxidant effect in the skeletal muscle of diabetic rats. In the present study,
      MnSOD activity was determined by spectrophotometry. The protein levels were
      evaluated by western blot analysis and mRNA content was quantified by RT-qPCR. We
      firstly found that the levels of AMP-activated protein kinase (AMPK), peroxisome
      proliferator-activated receptor coactivator 1alpha (PGC1alpha), silent mating
      type information regulation 2 homolog 3 (Sirt3) and manganese superoxide
      dismutase (MnSOD) were all decreased in the skeletal muscle of diabetic patients.
      Male rats with diabetes were also treated with the vehicle or with celastrol at
      1, 3 and 6 mg/kg/day for 8 weeks. The administration of celastrol at 3 and 6
      mg/kg attenuated the deterioration of skeletal muscle, as shown by histological
      analysis, decreased the malondialdehyde (MDA) level and increased the glutathione
      (GSH) level assayed by enzyme-linked immunosorbent assay (ELISA) method. It also
      enhanced the enzyme activity and increased the expression of MnSOD, and increased
      the AMPK phosphorylation level, as well as PGC1alpha and Sirt3 expression. The
      findings of our study suggest that the expression of AMPK, PGC1alpha, Sirt3 and
      MnSOD are decreased in the skeletal muscle of diabetic patients. Celastrol
      exerted antioxidant effects on skeletal muscle partly by regulating the AMPK
      PGC1alpha-Sirt3 signaling pathway.

PMID- 27049826
TI  - Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence: A
      Randomized Clinical Trial.
AB  - IMPORTANCE: Diacetylmorphine hydrochloride (the active ingredient in heroin),
      delivered under supervision, is effective for the treatment of severe opioid use
      disorder. However, owing to political and regulatory barriers, it is not
      available in many settings around the world, which limits the options for many
      long-term street opioid injectors not attracted into or retained in available
      treatments. OBJECTIVE: To test if injectable hydromorphone hydrochloride is
      noninferior to injectable diacetylmorphine in reducing illicit heroin use for
      chronic injection opioid users after 6 months of intervention. DESIGN, SETTING,
      AND PARTICIPANTS: The Study to Assess Longer-term Opioid Medication Effectiveness
      (SALOME) was a phase 3, double-blind, noninferiority trial. The study randomized
      202 long-term street opioid injectors in Vancouver, British Columbia, Canada.
      Eligible participants were recruited between December 19, 2011, and December 18,
      2013. Both intent-to-treat (ITT) and per-protocol (PP) analyses were conducted.
      INTERVENTIONS: Participants were randomly assigned to receive injectable
      diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under
      supervision. MAIN OUTCOMES AND MEASURES: Primary and coprimary efficacy outcomes
      were self-reported days of street heroin use (primary), days of any street
      acquired opioids in the prior 30 days (noninferiority margin, 4 days), and the
      proportion of urinalyses positive for street heroin markers (margin, 10% of the
      observed rate in the diacetylmorphine group). The mean differences between
      diacetylmorphine and hydromorphone for the ITT and PP analyses were reported.
      RESULTS: The study included 202 participants; 100 randomized to receive
      hydromorphone and 102 to diacetylmorphine. Their mean (SD) age was 44.33 (9.63)
      years, and 30.7% (62 of 202) were women. Noninferiority of hydromorphone was
      confirmed in the PP analysis (-1.44; 90% CI, -3.22 to 0.27) for street heroin
      use, although the margin of 4 days was not excluded in the ITT analysis (-2.34;
      90% CI, -4.14 to -0.52). Noninferiority was confirmed for any street opioids in
      the ITT analysis (-0.85; 90% CI, -2.97 to 1.25) and the PP analysis (-0.15; 90%
      CI, -2.09 to 1.76), as well as for the urinalyses (0.09; 90% CI, -0.02 to 0.19
      for the ITT analysis and 0.13; 90% CI, 0.02-0.24 for the PP analysis). There were
      29 SAEs considered to have some relationship with the injection medication, 5 in
      the hydromorphone group and 24 in the diacetylmorphine group (rate ratio, 0.21;
      95% CI, 0.06-0.69). Seizures and overdoses accounted for 25 of the 29 related
      SAEs. CONCLUSIONS AND RELEVANCE: This study provides evidence to suggest
      noninferiority of injectable hydromorphone relative to diacetylmorphine for long
      term opioid dependence. In jurisdictions where diacetylmorphine is currently not
      available or for patients in whom it is contraindicated or unsuccessful,
      hydromorphone could be offered as an alternative. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01447212.

PMID- 27049827
TI  - The platelet isoform of phosphofructokinase contributes to metabolic
      reprogramming and maintains cell proliferation in clear cell renal cell
      carcinoma.
AB  - Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC)
      progression include aerobic glycolysis, increased pentose phosphate pathway
      activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key
      enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue
      distributions. The mRNA level of the platelet isoform of phosphofructokinase
      (PFKP) is reported to be up-regulated in ccRCC patients. However, it remains
      unclear whether PFKP plays an important role in promoting aerobic glycolysis and
      macromolecular biosynthesis to support cell proliferation in ccRCC. Here we found
      that the up-regulated PFKP became the predominant isoform of PFK in human ccRCC.
      Suppression of PFKP not only impaired cell proliferation by inducing cell cycle
      arrest and apoptosis, but also led to decreased glycolysis, pentose phosphate
      pathway and nucleotide biosynthesis, accompanied by activated tricarboxylic acid
      cycle in ccRCC cells. Moreover, we found that p53 activation contributed to cell
      proliferation and metabolic defects induced by PFKP knockdown in ccRCC cells.
      Furthermore, suppression of PFKP led to reduced ccRCC tumor growth in vivo. Our
      data indicate that PFKP not only is required for metabolic reprogramming and
      maintaining cell proliferation, but also may provide us with a valid target for
      anti-renal cancer pharmaceutical agents. 

PMID- 27049828
TI  - Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP
      hAbetaPPswe/PS1DeltaE9 mice: potential mechanism underlying cognitive impairment.
AB  - Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP
      hAbetaPPswe/PS1DeltaE9 (APP/PS1) mice are classic animal models of sporadic
      Alzheimer's disease and familial AD respectively. Our study showed that object
      recognition memory, spatial learning and memory, active and passive avoidance
      were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance
      in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific
      phenotype of cognition, neuroendocrine, immune and NIM molecular network. The
      endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating
      hormone, chemotactic factor monocyte chemotactic protein-1, macrophage
      inflammatory protein-1beta, regulated upon activation normal T cell expressed and
      secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1
      cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice,
      while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony
      stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as
      humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T
      cell receptor signaling pathway played the key role in cognition impairments of
      two models, while cytokine-cytokine receptor interaction and natural killer cell
      mediated cytotoxicity were more important in cognitive deterioration of SAMP8
      mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive
      impairment is significant for further understanding the pathogenesis of AD and
      can provide useful information for development of AD therapeutic drug. 

PMID- 27049829
TI  - LGR5 expression is controled by IKKalpha in basal cell carcinoma through
      activating STAT3 signaling pathway.
AB  - Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The
      noncanonical NF-kappaB pathway is dependent on IKKalpha. However, the role of
      IKKalpha in BCC has not been elucidated. We show here that IKKalpha is expressed
      in the nucleus in BCC and non-malignant diseases. Nuclear IKKalpha could directly
      bind to the promoters of inflammation factors and LGR5, a stem cell marker, in
      turn, upregulating LGR5 expression through activation of STAT3 signaling pathway
      during cancer progression. Activation of STAT3 signaling pathway contributes LGR5
      expression in dependent of IKKalpha after the interplay between STAT3 and
      IKKalpha. Meanwhile knockdown of IKKalpha inhibits tumor growth and transition of
      epithelial stage to mescheme stage. Taken together, we demonstrate that IKKalpha
      functions as a bone fide chromatin regulator in BCC, whose promoted expression
      contributes to oncogenic transformation via promoting expression stemness- and
      inflammatory- related genes. Our finding reveals a novel viewpoint for how
      IKKalpha may involve in BCCs tumor progression in the inflammatory
      microenvironment. 

PMID- 27049830
TI  - Distinct epigenetic signatures elucidate enhancer-gene relationships that
      delineate CIMP and non-CIMP colorectal cancers.
AB  - Epigenetic changes, like DNA methylation, affect gene expression and in
      colorectal cancer (CRC), a distinct phenotype called the CpG island methylator
      phenotype ("CIMP") has significantly higher levels of DNA methylation at so
      called "Type C loci" within the genome. We postulate that enhancer-gene pairs are
      coordinately controlled through DNA methylation in order to regulate the
      expression of key genes/biomarkers for a particular phenotype.Firstly, we found
      24 experimentally-validated enhancers (VISTA enhancer browser) that contained
      statistically significant (FDR-adjusted q-value of <0.01) differentially
      methylated regions (DMRs) (1000bp) in a study of CIMP versus non-CIMP CRCs. Of
      these, the methylation of 2 enhancers, 1702 and 1944, were found to be very well
      correlated with the methylation of the genes Wnt3A and IGDCC3, respectively, in
      two separate and independent datasets.We show for the first time that there are
      indeed distinct and dynamic changes in the methylation pattern of specific
      enhancer-gene pairs in CRCs. Such a coordinated epigenetic event could be
      indicative of an interaction between (1) enhancer 1702 and Wnt3A and (2) enhancer
      1944 and IGDCC3. Moreover, our study shows that the methylation patterns of these
      2 enhancer-gene pairs can potentially be used as biomarkers to delineate CIMP
      from non-CIMP CRCs. 

PMID- 27049831
TI  - Analysis of tumor template from multiple compartments in a blood sample provides
      complementary access to peripheral tumor biomarkers.
AB  - Targeted cancer therapeutics are promised to have a major impact on cancer
      treatment and survival. Successful application of these novel treatments requires
      a molecular definition of a patient's disease typically achieved through the use
      of tissue biopsies. Alternatively, allowing longitudinal monitoring, biomarkers
      derived from blood, isolated either from circulating tumor cell derived DNA
      (ctcDNA) or circulating cell-free tumor DNA (ccfDNA) may be evaluated. In order
      to use blood derived templates for mutational profiling in clinical decisions, it
      is essential to understand the different template qualities and how they compare
      to biopsy derived template DNA as both blood-based templates are rare and
      distinct from the gold-standard. Using a next generation re-sequencing strategy,
      concordance of the mutational spectrum was evaluated in 32 patient-matched ctcDNA
      and ccfDNA templates with comparison to tissue biopsy derived DNA template.
      Different CTC antibody capture systems for DNA isolation from patient blood
      samples were also compared. Significant overlap was observed between ctcDNA,
      ccfDNA and tissue derived templates. Interestingly, if the results of ctcDNA and
      ccfDNA template sequencing were combined, productive samples showed similar
      detection frequency (56% vs 58%), were temporally flexible, and were
      complementary both to each other and the gold standard. These observations
      justify the use of a multiple template approach to the liquid biopsy, where
      germline, ctcDNA, and ccfDNA templates are employed for clinical diagnostic
      purposes and open a path to comprehensive blood derived biomarker access. 

PMID- 27049832
TI  - Ki-67 proliferation index but not mitotic thresholds integrates the molecular
      prognostic stratification of lower grade gliomas.
AB  - Despite several molecular signatures for "lower grade diffuse gliomas" (LGG) have
      been identified, WHO grade still remains a cornerstone of treatment guidelines.
      Mitotic count bears a crucial role in its definition, although limited by the
      poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho
      histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular
      proliferation. Therefore in the present series of 141 LGG, the molecular
      characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter
      methylation) was integrated with the tumor "proliferative trait" (conventional
      H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis
      definition. Exclusively high PHH3 and Ki-67 values were predictor of poor
      prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike
      standard mitotic count. Based on Cox proportional hazard regression analyses,
      among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables
      (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at
      univariate survival analysis, only IDH expression (P = 0.001) and Ki-67
      proliferation index (P = 0.027) proved to be independent prognostic factors. In
      addition, stratifying by IDH expression status, high Ki-67 retained its
      prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling
      their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the
      sole reliable method with a prognostic value to highlight mitotic figures in LGG.
      Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's
      prognosis, and should be integrated with molecular markers in a comprehensive
      grading system for LGG. 

PMID- 27049833
TI  - Role of p85alpha in neutrophil extra- and intracellular reactive oxygen species
      generation.
AB  - Drug resistance is a growing problem that necessitates new strategies to combat
      pathogens. Neutrophil phagocytosis and production of intracellular ROS, in
      particular, has been shown to cooperate with antibiotics in the killing of
      microbes. This study tested the hypothesis that p85alpha, the regulatory subunit
      of PI3K, regulates production of intracellular ROS. Genetic knockout of p85alpha
      in mice caused decreased expression of catalytic subunits p110alpha, p110beta,
      and p110delta, but did not change expression levels of the NADPH oxidase complex
      subunits p67phox, p47phox, and p40phox. When p85alpha, p55alpha, and p50alpha
      (all encoded by Pik3r1) were deleted, there was an increase in intracellular ROS
      with no change in phagocytosis in response to both Fcgamma receptor and
      complement receptor stimulation. Furthermore, the increased intracellular ROS
      correlated with significantly improved neutrophil killing of both methicillin
      susceptible and methicillin-resistant S. aureus. Our findings suggest inhibition
      of p85alpha as novel approach to improving the clearance of resistant pathogens. 

PMID- 27049834
TI  - Anti-cancer effects of curcumin on lung cancer through the inhibition of EZH2 and
      NOTCH1.
AB  - Curcumin is potentially therapeutic for malignant diseases. The mechanisms of
      this effect might involve a combination of antioxidant, immunomodulatory,
      proapoptotic, and antiangiogenic activities. However, the exact mechanisms are
      not fully understood. In the present study, we provided evidences that curcumin
      suppressed the expression of enhancer of zeste homolog 2 (EZH2) in lung cancer
      cells both transcriptionally and post-transcriptionally. Curcumin inhibited the
      expression of EZH2 through microRNA (miR)-let 7c and miR-101. Curcumin decreased
      the expression of NOTCH1 through the inhibition of EZH2. There was a reciprocal
      regulation between EZH2 and NOTCH1 in lung cancer cells. These observations
      suggest that curcumin inhibits lung cancer growth and metastasis at least partly
      through the inhibition of EZH2 and NOTCH1. 

PMID- 27049835
TI  - Speech recognition outcomes following bilateral cochlear implantation in adults
      aged over 50 years old.
AB  - OBJECTIVE: To examine the speech recognition benefit of bilateral cochlear
      implantation over unilateral implantation in adults aged over 50 years old, and
      to identify potential predictors of successful bilateral implantation in this
      group. DESIGN: Retrospective cohort study using data collected during standard
      clinical practice. Bilateral performance was compared to the unilateral
      performance with the first and second implanted ear and examined in relation to
      potential predictive variables. STUDY SAMPLE: Sixty-seven cochlear implant users
      who received a second implant after the age of 50 years old. RESULTS:
      Participants obtained significantly greater speech recognition scores with the
      use of bilateral cochlear implants compared to the use of each individual
      implant. The score obtained with the first implanted ear was the most reliable
      predictor of the score obtained with the second and with bilateral implants.
      CONCLUSIONS: Older adults can obtain speech recognition benefits from sequential
      bilateral cochlear implantation.

PMID- 27049836
TI  - Association of depressive/anxiety symptoms with quality of life and work ability
      in patients with systemic lupus erythematosus.
AB  - OBJECTIVES: To study the association of depressive/anxiety symptoms with health
      related quality of life (HRQoL) and work ability in Chinese patients with
      systemic lupus erythematosus (SLE). METHODS: Consecutive patients with >=4 ACR
      criteria for SLE were recruited. Depressive and anxiety symptoms were assessed by
      the Hospital Anxiety and Depression scale (HADS). HRQoL was assessed by the
      Chinese version of MOS-Short Form (SF)-36. Disease activity of SLE was assessed
      by the SLE disease activity index (SLEDAI) and organ damage was assessed by the
      ACR/SLICC damage index (SDI). The relationship between HAD scores, work ability
      and HRQoL was studied. RESULTS: A total of 367 SLE patients were studied (95%
      women; age 40.2+/-12.9 years; disease duration 9.3+/-7.2 years). Fifty-five (15%)
      patients had HADS-depression score >=10 and 70 (19%) patients had HADS-anxiety
      score >=10. Patients with either score >=10 had significantly lower SF36 score
      (physical and mental component) than those with score <10. In separate linear
      regression models, the mental and physical component scores of SF36 were
      significantly associated with the HAD-depression and HAD-anxiety score after
      adjustment for age, sex, SLE duration, years of education, religious belief,
      marital status, employment status, poverty, SDI and mean SLEDAI score in the
      preceding year. Among those who were working in the preceding year (n=190),
      30(16%) patients either quitted their job (n=22) or reduced working hours (n=8).
      Patients with work disability had significantly higher HAD-depression score than
      those without (6.31+/-5.51 vs 3.93+/-3.72; p=0.03). CONCLUSIONS:
      Depressive/anxiety symptoms were fairly common in SLE patients and independently
      associated with poorer HRQoL. Patients with more depressive symptoms were more
      likely to experience work disability.

PMID- 27049837
TI  - Impact of hole doping on spin transition in perovskite-type cobalt oxides.
AB  - Series of perovskite PrCo1-xNixO3-delta (x = 0-0.4) were prepared and carefully
      investigated to understand the spin state transition driven by hole doping and
      further to reveal the effect of spin state transition on electronic conduction.
      It is shown that with increasing doping level, the transition temperature Ts for
      Co(3+) ions from low-spin (LS) to intermediate-spin (IS) reduces from 211.9 K for
      x = 0 to 190.5 K for x = 0.4. XPS and FT-IR spectra demonstrate that hole doping
      promoted this transition due to a larger Jahn-Teller distortion. Moreover, a
      thermal activation of spin disorder caused by thermal population of the spin
      states for Co ions has a great impact on the electrical transport of these
      perovskite samples. This work may shed light on the comprehension of spin
      transition in cobalt oxides through hole doping, which is promising for finding
      new strategies of enhancing electronic conduction, especially for energy and
      catalysis applications. 

PMID- 27049838
TI  - Cost-Effectiveness of Becaplermin Gel on Diabetic Foot Ulcer HealingChanges in
      Wound Surface Area.
AB  - BACKGROUND: A comparison of the cost-effectiveness of becaplermin plus good wound
      care (BGWC) versus good wound care (GWC) alone in treating patients with diabetic
      foot ulcers (DFUs) may enable physicians and health-care decision makers in the
      United States to make better-informed choices about treating DFUs, which
      currently contribute to a substantial portion of the economic burden of diabetes.
      METHODS: Data from three phase III trials were used to predict expected 1-year
      costs and outcomes, including the average percentage reduction from baseline in
      wound surface area (WSA), the direct costs of DFU therapy, and the cost per cm(2)
      of WSA reduction. RESULTS: At 20 weeks, the BGWC group had a statistically
      greater probability of complete wound closure than the GWC group (50% versus 35%;
      P = .015). Based on reported WSA reduction rates, DFUs in the BGWC group were
      predicted to close by 100% at 27 weeks, and those in the GWC group were predicted
      to close by 88% at 52 weeks. The GWC group had higher total estimated 1-year
      direct cost of DFU care ($6,809 versus $4,414) and higher cost per cm(2) of wound
      closure ($3,501 versus $2,006). CONCLUSIONS: Becaplermin plus good wound care
      demonstrated economic dominance compared with GWC by providing better clinical
      outcomes via faster reduction in WSA and higher rates of closure at a lower
      direct cost.

PMID- 27049839
TI  - Anterior Cervical Corpectomy Non-Fusion Model Produced by a Novel Implant.
AB  - BACKGROUND: Anterior cervical corpectomy and fusion are frequently used in the
      treatment of cervical spinal disease. However, the range of motion (ROM) of the
      operative level is unavoidably lost due to fusion. This study aims to establish
      an anterior cervical corpectomy goat non-fusion model and to evaluate the ROM of
      adjacent and operative levels. MATERIAL/METHODS: Six adult-male goats (in vivo
      group) and twelve adult-male goat cervical spine specimens (randomly divided
      equally into intact group or in vitro group) were included. The non-fusion model
      was established by implanting a novel implant at C4 level. Imagiological
      examinations for the in vivo group were performed to inspect the position of the
      implant and spinal cord status. Specimens were harvested six months after the
      operation. Biomechanical testing was conducted to obtain the ROM in flexion
      extension, lateral bending, and axial rotation at upper adjacent level (C(2-3)),
      operative levels (C(3-4) and C(4-5)) and at C(2-5). Specimens in the intact group
      were first tested as intact and then tested as fixed and became the fixation
      group. RESULTS: Imagiological examinations revealed that the position of the
      implant and the spinal cord status were good. The specimens in the in vivo and in
      vitro groups had significantly decreased C(2-3) ROM, increased C(3-4) and C(4-5)
      ROM and similar C(2-5) ROM compared with the fixation group. CONCLUSIONS: This
      study presents a novel method for potential non-fusion treatment strategies for
      cervical spinal disease. However, improvement of this model and additional
      studies are needed.

PMID- 27049840
TI  - Monodisperse Cylindrical Micelles and Block Comicelles of Controlled Length in
      Aqueous Media.
AB  - Cylindrical block copolymer micelles have shown considerable promise in various
      fields of biomedical research. However, unlike spherical micelles and vesicles,
      control over their dimensions in biologically relevant solvents has posed a key
      challenge that potentially limits in depth studies and their optimization for
      applications. Here, we report the preparation of cylindrical micelles of length
      in the wide range of 70 nm to 1.10 MUm in aqueous media with narrow length
      distributions (length polydispersities <1.10). In our approach, an amphiphilic
      linear-brush block copolymer, with high potential for functionalization, was
      synthesized based on poly(ferrocenyldimethylsilane)-b-poly(allyl glycidyl ether)
      (PFS-b-PAGE) decorated with triethylene glycol (TEG), abbreviated as PFS-b-(PEO-g
      TEG). PFS-b-(PEO-g-TEG) cylindrical micelles of controlled length with low
      polydispersities were prepared in N,N-dimethylformamide using small seed
      initiators via living crystallization-driven self-assembly. Successful dispersion
      of these micelles into aqueous media was achieved by dialysis against deionized
      water. Furthermore, B-A-B amphiphilic triblock comicelles with PFS-b-poly(2
      vinylpyridine) (P2VP) as hydrophobic "B" blocks and hydrophilic PFS-b-(PEO-g-TEG)
      "A" segments were prepared and their hierarchical self-assembly in aqueous media
      studied. It was found that superstructures formed are dependent on the length of
      the hydrophobic blocks. Quaternization of P2VP was shown to cause the disassembly
      of the superstructures, resulting in the first examples of water-soluble
      cylindrical multiblock comicelles. We also demonstrate the ability of the
      triblock comicelles with quaternized terminal segments to complex DNA and, thus,
      to potentially function as gene vectors. 

PMID- 27049841
TI  - The use of exploratory analyses within the National Institute for Health and Care
      Excellence single technology appraisal process: an evaluation and qualitative
      analysis.
AB  - BACKGROUND: As part of the National Institute for Health and Care Excellence
      (NICE) single technology appraisal (STA) process, independent Evidence Review
      Groups (ERGs) critically appraise the company submission. During the critical
      appraisal process the ERG may undertake analyses to explore uncertainties around
      the company's model and their implications for decision-making. The ERG reports
      are a central component of the evidence considered by the NICE Technology
      Appraisal Committees (ACs) in their deliberations. OBJECTIVE: The aim of this
      research was to develop an understanding of the number and type of exploratory
      analyses undertaken by the ERGs within the STA process and to understand how
      these analyses are used by the NICE ACs in their decision-making. METHODS: The
      100 most recently completed STAs with published guidance were selected for
      inclusion in the analysis. The documents considered were ERG reports,
      clarification letters, the first appraisal consultation document and the final
      appraisal determination. Over 400 documents were assessed in this study. The
      categories of types of exploratory analyses included fixing errors, fixing
      violations, addressing matters of judgement and the ERG-preferred base case. A
      content analysis of documents (documentary analysis) was undertaken to identify
      and extract relevant data, and narrative synthesis was then used to rationalise
      and present these data. RESULTS: The level and type of detail in ERG reports and
      clarification letters varied considerably. The vast majority (93%) of ERG reports
      reported one or more exploratory analyses. The most frequently reported type of
      analysis in these 93 ERG reports related to the category 'matters of judgement',
      which was reported in 83 (89%) reports. The category 'ERG base-case/preferred
      analysis' was reported in 45 (48%) reports, the category 'fixing errors' was
      reported in 33 (35%) reports and the category 'fixing violations' was reported in
      17 (18%) reports. The exploratory analyses performed were the result of issues
      raised by an ERG in its critique of the submitted economic evidence. These
      analyses had more influence on recommendations earlier in the STA process than
      later on in the process. LIMITATIONS: The descriptions of analyses undertaken
      were often highly specific to a particular STA and could be inconsistent across
      ERG reports and thus difficult to interpret. CONCLUSIONS: Evidence Review Groups
      frequently conduct exploratory analyses to test or improve the economic
      evaluations submitted by companies as part of the STA process. ERG exploratory
      analyses often have an influence on the recommendations produced by the ACs.
      FUTURE WORK: More in-depth analysis is needed to understand how ERGs make
      decisions regarding which exploratory analyses should be undertaken. More
      research is also needed to fully understand which types of exploratory analyses
      are most useful to ACs in their decision-making. FUNDING: The National Institute
      for Health Research Health Technology Assessment programme.

PMID- 27049842
TI  - Tunable charge transfer properties in metal-phthalocyanine heterojunctions.
AB  - Organic materials such as phthalocyanine-based systems present a great potential
      for organic device applications due to the possibility of integrating films of
      different organic materials to create organic heterostructures which combine the
      electrical capabilities of each material. This opens the possibility to precisely
      engineer and tune new electrical properties. In particular, similar transition
      metal phthalocyanines demonstrate hybridization and charge transfer properties
      which could lead to interesting physical phenomena. Although, when considering
      device dimensions, a better understanding and control of the tuning of the
      transport properties still remain in the focus of research. Here, by employing
      conductive atomic force microscopy techniques, we provide an insight about the
      nanoscale electrical properties and transport mechanisms of MnPc and fluorinated
      phthalocyanines such as F16CuPc and F16CoPc. We report a transition from typical
      diode-like transport mechanisms for pure MnPc thin films to space-charge-limited
      current transport regime (SCLC) for Pc-based heterostructures. The controlled
      addition of fluorinated phthalocyanine also provides highly uniform and symmetric
      polarized transport characteristics with conductance enhancements up to two
      orders of magnitude depending on the polarization. We present a method to
      spatially map the mobility of the MnPc/F16CuPc structures with a nanoscale
      resolution and provide theoretical calculations to support our experimental
      findings. This well-controlled nanoscale tuning of the electrical properties for
      metal transition phthalocyanine junctions stands as key step for future
      phthalocyanine-based electronic devices, where the low dimension charge transfer,
      mediated by transition metal atoms could be intrinsically linked to a transfer of
      magnetic moment or spin. 

PMID- 27049843
TI  - Patching the Exchange-Correlation Potential in Density Functional Theory.
AB  - A method for directly patching exchange-correlation (XC) potentials in materials
      is derived. The electron density of a system is partitioned into subsystem
      densities by dividing its Kohn-Sham (KS) potential among the subsystems. Inside
      each subsystem, its projected KS potential is required to become the total
      system's KS potential. This requirement, together with the nearsightedness
      principle of electronic matters, ensures that the electronic structures inside
      subsystems can be good approximations to the total system's electronic structure.
      The nearsightedness principle also ensures that subsystem densities could be well
      localized in their regions, making it possible to use high-level methods to
      invert the XC potentials for subsystem densities. Two XC patching methods are
      developed. In the local XC patching method, the total system's XC potential is
      improved in the cluster region. We show that the coupling between a cluster and
      its environment is important for achieving a fast convergence of the electronic
      structure in the cluster region. In the global XC patching method, we discuss how
      to patch the subsystem XC potentials to construct the XC potential in the total
      system, aiming to scale up high-level quantum mechanics simulations of materials.
      Proof-of-principle examples are given. 

PMID- 27049844
TI  - Conformational diversity and enantioconvergence in potato epoxide hydrolase 1.
AB  - Potato epoxide hydrolase 1 (StEH1) is a biocatalytically important enzyme that
      exhibits rich enantio- and regioselectivity in the hydrolysis of chiral epoxide
      substrates. In particular, StEH1 has been demonstrated to enantioconvergently
      hydrolyze racemic mixes of styrene oxide (SO) to yield (R)-1-phenylethanediol.
      This work combines computational, crystallographic and biochemical analyses to
      understand both the origins of the enantioconvergent behavior of the wild-type
      enzyme, as well as shifts in activities and substrate binding preferences in an
      engineered StEH1 variant, R-C1B1, which contains four active site substitutions
      (W106L, L109Y, V141K and I155V). Our calculations are able to reproduce both the
      enantio- and regioselectivities of StEH1, and demonstrate a clear link between
      different substrate binding modes and the corresponding selectivity, with the
      preferred binding modes being shifted between the wild-type enzyme and the R-C1B1
      variant. Additionally, we demonstrate that the observed changes in selectivity
      and the corresponding enantioconvergent behavior are due to a combination of
      steric and electrostatic effects that modulate both the accessibility of the
      different carbon atoms to the nucleophilic side chain of D105, as well as the
      interactions between the substrate and protein amino acid side chains and active
      site water molecules. Being able to computationally predict such subtle effects
      for different substrate enantiomers, as well as to understand their origin and
      how they are affected by mutations, is an important advance towards the
      computational design of improved biocatalysts for enantioselective synthesis. 

PMID- 27049845
TI  - Fluorescent Polystyrene Microbeads as Invisible Security Ink and Optical Vapor
      Sensor for 4-Nitrotoluene.
AB  - Color-tunable solid-state emitting polystyrene (PS) microbeads were developed by
      dispersion polymerization, which showed excellent fluorescent security ink
      characteristics along with sensitive detection of vapors of nitro aromatics like
      4-nitro toluene (4-NT). The fluorophores pyrene and perylenebisimide were
      incorporated into the PS backbone as acrylate monomer and acrylate cross-linker,
      respectively. Solid state quantum yields of 94 and 20% were observed for the
      pyrene and perylenebisimide, respectively, in the PS/Py and PS/PBI polymers. The
      morphology and solid state fluorescence was measured by SEM, fluorescence
      microscopy, and absorbance and fluorescence spectroscopy techniques. The ethanol
      dispersion of the polymer could be used directly as a fluorescent security
      "invisible" ink, which became visible only under ultraviolet light. The color of
      the ink could be tuned depending on the amounts of the pyrene and
      perylenebisimide incorporated with blue and orange-green for pyrene alone or
      perylenebisimide alone beads respectively and various shades in between including
      pure white for beads incorporating both the fluorophores. More than 80% quenching
      of pyrene emission was observed upon exposure of the polymer in the form of
      powder or as spin-coated films to the vapors of 4-NT while the emission of
      perylenebisimide was unaffected. The limit of detection was estimated at 10(-5)
      moles (2.7 ppm) of 4-NT vapors. The ease of synthesis of the material along with
      its invisible ink characteristics and nitro aromatic vapor detection opens up new
      opportunities for exploring the application of these PS-based materials as
      optical sensors and fluorescent ink for security purposes.

PMID- 27049846
TI  - Binding of the Cationic Peptide (KL)4K to Lipid Monolayers at the Air-Water
      Interface: Effect of Lipid Headgroup Charge, Acyl Chain Length, and Acyl Chain
      Saturation.
AB  - The binding of the cationic peptide (KL)4K to monolayers of different anionic
      lipids was determined by adsorption experiments. The chemical structure of the
      anionic phospholipids was changed in different ways. First, the hydrophobic
      region of phosphatidylglycerols was altered by elongation of the acyl chain
      length. Second, an unsaturated chain was introduced. Third, lipids with
      negatively charged headgroups of different chemical structure were compared.
      (KL)4K itself shows no surface activity and does not bind to monolayers of
      zwitterionic lipids. Analysis of (KL)4K binding to anionic lipid monolayers
      reveals a competition between two binding processes: (i) incorporation of the
      peptide into the acyl chain region (surface pressure increase) and (ii)
      electrostatic interaction screening the negative charges with reduction of charge
      repulsion (surface pressure decrease due to monolayer condensation). The lipid
      acyl chain length and the chemical structure of the headgroup have minor effects
      on the binding properties. However, a strong dependence on the phase state of the
      monolayer was observed. In the liquid-expanded (LE) phase, the fluid monolayer
      provides enough space, so that peptide insertion due to hydrophobic interactions
      dominates. For monolayers in the liquid-condensed (LC) phase, peptide binding
      followed by monolayer condensation is the main effect.

PMID- 27049847
TI  - Fano resonance of Li-doped KTa(1-x)NbxO3 single crystals studied by Raman
      scattering.
AB  - The enhancement of functionality of perovskite ferroelectrics by local structure
      is one of current interests. By the Li-doping to KTa(1-x)NbxO3 (KTN), the large
      piezoelectric and electro-optic effects were reported. In order to give new
      insights into the mechanism of doping, the microscopic origin of the Fano
      resonance induced by the local structure was investigated in 5%Li-doped KTN
      single crystals by Raman scattering. The coupling between the continuum states
      and the transverse optical phonon near 196 cm(-1) (Slater mode) caused a Fano
      resonance. In the vicinity of the cubic-tetragonal phase transition temperature,
      TC-T = 31  degrees C, the almost disappearance of the Fano resonance and the
      remarkable change of the central peak (CP) intensity were observed upon heating.
      The local symmetry of the polar nanoregions (PNRs), which was responsible for the
      symmetry breaking in the cubic phase, was determined to E(x, y) symmetry by the
      angular dependence of Raman scattering. The electric field induced the
      significant change in the intensity of both CP and Fano resonance. From these
      experimental results, it is concluded that the origin of the Fano resonance in Li
      doped KTN crystals is the coupling between polarization fluctuations of PNRs and
      the Slater mode, both belong to the E(x, y) symmetry.

PMID- 27049848
TI  - A Fluorescent Readout for the Oxidation State of Electron Transporting Proteins
      in Cell Free Settings.
AB  - Pathways involving sequential electron transfer between multiple proteins are
      ubiquitous in nature. Here, we demonstrate a new class of fluorescent protein
      based reporters for monitoring electron transport through such multistage
      cascades, specifically those involving ferredoxin-like electron transporters. We
      created protein fusions between mammalian Adrenodoxin (Adx) and plant Ferredoxin
      (Fdx) with fluorescent proteins of different colors and found that the
      fluorescence of such fusions is highly sensitive to the redox state of the
      electron transporter. The increase in fluorescence from the oxidized to the
      reduced state was inversely proportional to the linker length between the fusion
      partners. We first used our approach to quantitatively characterize electron
      transfer from NADPH through Adrenodoxin Reductase (AdR) to Adrenodoxin (Adx). Our
      data allowed us to build a detailed mathematical model of this mitochondrial
      electron transfer chain and validate previously proposed mechanisms. Then, we
      showed that an Adx-GFP fusion could serve as a sensor for the activity of
      bacterial Type I Cytochrome P450s (CYPs), a very large class of enzymes with
      important roles in biotechnology. We further showed that fluorescence of a direct
      fusion between CYP and GFP was sensitive to CYP activity, suggesting that our
      approach is applicable to an even broader class of proteins, which undergo a
      redox state change during their work cycle.

PMID- 27049849
TI  - Behavior Based Social Dimensions Extraction for Multi-Label Classification.
AB  - Classification based on social dimensions is commonly used to handle the multi
      label classification task in heterogeneous networks. However, traditional
      methods, which mostly rely on the community detection algorithms to extract the
      latent social dimensions, produce unsatisfactory performance when community
      detection algorithms fail. In this paper, we propose a novel behavior based
      social dimensions extraction method to improve the classification performance in
      multi-label heterogeneous networks. In our method, nodes' behavior features,
      instead of community memberships, are used to extract social dimensions. By
      introducing Latent Dirichlet Allocation (LDA) to model the network generation
      process, nodes' connection behaviors with different communities can be extracted
      accurately, which are applied as latent social dimensions for classification.
      Experiments on various public datasets reveal that the proposed method can obtain
      satisfactory classification results in comparison to other state-of-the-art
      methods on smaller social dimensions. 

PMID- 27049850
TI  - Biomarkers in Exhaled Breath Condensate Are Not Predictive for Pulmonary
      Exacerbations in Children with Cystic Fibrosis: Results of a One-Year
      Observational Study.
AB  - BACKGROUND: Cystic Fibrosis (CF) is characterized by chronically inflamed
      airways, and inflammation even increases during pulmonary exacerbations. These
      adverse events have an important influence on the well-being, quality of life,
      and lung function of patients with CF. Prediction of exacerbations by
      inflammatory markers in exhaled breath condensate (EBC) combined with early
      treatment may prevent these pulmonary exacerbations and may improve the
      prognosis. AIM: To investigate the diagnostic accuracy of a set of inflammatory
      markers in EBC to predict pulmonary exacerbations in children with CF. METHODS:
      In this one-year prospective observational study, 49 children with CF were
      included. During study visits with an interval of 2 months, a symptom
      questionnaire was completed, EBC was collected, and lung function measurements
      were performed. The acidity of EBC was measured directly after collection.
      Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF
      alpha), and macrophage migration inhibitory factor (MIF) were measured using high
      sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded
      during the study and were defined in two ways. The predictive power of
      inflammatory markers and the other covariates was assessed using conditionally
      specified models and a receiver operating characteristic curve (SAS version 9.2).
      In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2).
      RESULTS: Sixty-five percent of the children had one or more exacerbations during
      the study. The conditionally specified models showed an overall correct
      prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The
      results obtained with the KNN algorithm were very similar. CONCLUSION: Although
      there is some evidence indicating that the predictors outperform random guessing,
      the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers
      IL-6, IL-8, TNF-alpha and MIF is low. At present it is not possible to predict
      pulmonary exacerbations in children with CF with the chosen biomarkers and the
      method of EBC analysis. The biochemical measurements of EBC markers should be
      improved and other techniques should be considered.

PMID- 27049851
TI  - Evidence of Premeditation in Skin Messages in Suicide.
AB  - A 34-year-old man with manic-depressive disorder was found dead sitting in a
      vehicle with a hose running from the exhaust pipe to the cabin. Numerous suicide
      notes were found inside his house. At autopsy, the decedent was wearing jeans and
      a long-sleeved windcheater. Upon removal of his clothes, a series of messages
      were also found written on the legs and forearm. Death was due to carbon monoxide
      toxicity with a blood level of carboxyhemoglobin of 84%. Skin messages represent
      a rare form of suicide note that may suggest that a suicide has not been planned,
      as the decedent may have used the nearest surface to write on. This case
      demonstrates, however, that skin messages may be more organized, being written
      prior to dressing and setting up the fatal episode. They also may compliment
      other notes and messages. 

PMID- 27049852
TI  - Models of Individual Dietary Behavior Based on Smartphone Data: The Influence of
      Routine, Physical Activity, Emotion, and Food Environment.
AB  - INTRODUCTION: Smartphone applications (apps) facilitate the collection of data on
      multiple aspects of behavior that are useful for characterizing baseline patterns
      and for monitoring progress in interventions aimed at promoting healthier
      lifestyles. Individual-based models can be used to examine whether behavior, such
      as diet, corresponds to certain typological patterns. The objectives of this
      paper are to demonstrate individual-based modeling methods relevant to a person's
      eating behavior, and the value of such approach compared to typical regression
      models. METHOD: Using a mobile app, 2 weeks of physical activity and ecological
      momentary assessment (EMA) data, and 6 days of diet data were collected from 12
      university students recruited from a university in Kunming, a rapidly developing
      city in southwest China. Phone GPS data were collected for the entire 2-week
      period, from which exposure to various food environments along each subject's
      activity space was determined. Physical activity was measured using phone
      accelerometry. Mobile phone EMA was used to assess self-reported
      emotion/feelings. The portion size of meals and food groups was determined from
      voice-annotated videos of meals. Individual-based regression models were used to
      characterize subjects as following one of 4 diet typologies: those with a routine
      portion sizes determined by time of day, those with portion sizes that balance
      physical activity (energy balance), those with portion sizes influenced by
      emotion, and those with portion sizes associated with food environments. RESULTS:
      Ample compliance with the phone-based behavioral assessment was observed for all
      participants. Across all individuals, 868 consumed food items were recorded, with
      fruits, grains and dairy foods dominating the portion sizes. On average, 218
      hours of accelerometry and 35 EMA responses were recorded for each participant.
      For some subjects, the routine model was able to explain up to 47% of the
      variation in portion sizes, and the energy balance model was able to explain over
      88% of the variation in portion sizes. Across all our subjects, the food
      environment was an important predictor of eating patterns. Generally, grouping
      all subjects into a pooled model performed worse than modeling each individual
      separately. CONCLUSION: A typological modeling approach was useful in
      understanding individual dietary behaviors in our cohort. This approach may be
      applicable to the study of other human behaviors, particularly those that collect
      repeated measures on individuals, and those involving smartphone-based behavioral
      measurement.

PMID- 27049853
TI  - Growth of HIV-Exposed Uninfected Infants in the First 6 Months of Life in South
      Africa: The IeDEA-SA Collaboration.
AB  - BACKGROUND: HIV-exposed uninfected (HEU) infants are a growing population in sub
      Saharan Africa especially with the increasing coverage of more effective
      prevention of mother-to-child transmission (PMTCT) antiretroviral therapy
      regimens. This study describes the characteristics of South African HEU infants,
      investigates factors impacting birth weight and assesses their growth within the
      first 28 weeks of life. METHODS: This is a retrospective cohort based on routine
      clinical data from two South African PMTCT programmes. Data were collected
      between 2007 and 2013. Linear regression assessed factors affecting birth weight
      for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed
      effects models. RESULTS: We assessed the growth of 2621 HEU infants (median birth
      WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities
      practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with
      unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers
      with CD4 <200 cells/MUl delivered infants with a lower birth WAZ (adjusted beta 
      0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 >=500
      cells/MUl. Similarly, mothers who did not receive antiretroviral drugs delivered
      infants with a lower birth WAZ (adjusted beta -0.39 [95% CI -0.67; -0.11], p =
      0.007) compared to mothers who received antenatal antiretrovirals. Infants with a
      birth weight <2 500g (beta 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced
      faster growth within the first 28 weeks of life compared to infants with a birth
      weight >=2 500g. Infants with any breastfeeding exposure experienced slower
      longitudinal growth compared to formula fed infants (adjusted beta -0.012 [95% CI
      0.021; -0.003], p = 0.011). CONCLUSION: Less severe maternal disease and the use
      of antiretrovirals positively impacts birth weight in this cohort of South
      African HEU infants. Formula feeding was common with breastfed infants
      experiencing marginally slower longitudinal growth.

PMID- 27049854
TI  - Antioxidant activities and molecular mechanisms of the ethanol extracts of
      Baccharis propolis and Eucalyptus propolis in RAW64.7 cells.
AB  - Context Numerous studies have reported that propolis possesses strong antioxidant
      activities. However, their antioxidant molecular mechanisms are unclear.
      Objective We utilize ethanol extracts of Chinese propolis (EECP) as a reference
      to compare ethanol extracts of Eucalyptus propolis (EEEP) with ethanol extracts
      of Baccharis propolis (EEBGP) based on their antioxidant capacities and
      underlying molecular mechanisms. Materials and methods HPLC and chemical analysis
      are utilized to evaluate compositions and antioxidant activities. ROS-eliminating
      effects of EEBGP (20-75 MUg/mL), EEEP (1.25-3.75 MUg/mL) and EECP (1.25-5 MUg/mL)
      are also determined by flow cytometry analysis. Moreover, we compared antioxidant
      capacities by determining their effects on expressions of antioxidant genes in
      RAW264.7 cells with qRT-PCR, western blot and confocal microscopy analysis.
      Results EEBGP mainly contains chlorogenic acid (8.98 +/- 0.86 mg/g), kaempferide
      (11.18 +/- 8.31 mg/g) and artepillin C (107.70 +/- 10.86 mg/g), but EEEP contains
      10 compositions, whereas EECP contains 17 compositions. Meantime, although EEEP
      shows DPPH (IC50 19.55 +/- 1.28), ABTS (IC50 20.0 +/- 0.31) and reducing power
      (2.70 +/- 0.08 mmol TE/g) better than EEBGP's DPPH (IC50 43.85 +/- 0.54), ABTS
      (IC50 38.2 +/- 0.33) and reducing power (1.53 +/- 0.05 mmol TE/g), EEBGP exerts
      much higher ROS inhibition rate (40%) than EEEP (under 20%). Moreover, EEBGP
      strengthen antioxidant system by activating p38/p-p38 and Erk/p-Erk kinase via
      accelerating nucleus translocation of Nrf2. EEEP and EECP improve antioxidant
      gene expression only via Erk/p-Erk kinase-Nrf2 signalling pathway. Discussion and
      conclusion EEBGP and EEEP exert antioxidant activities via different molecular
      mechanisms, which may depend on chemical compositions. 

PMID- 27049855
TI  - Children's planning performance in the Zoo Map task (BADS-C): Is it driven by
      general cognitive ability, executive functioning, or prospection?
AB  - A minimal amount of research has examined the cognitive predictors of children's
      performance in naturalistic, errand-type planning tasks such as the Zoo Map task
      of the Behavioral Assessment of the Dysexecutive Syndrome for Children (BADS-C).
      Thus, the current study examined prospection (i.e., the ability to remember to
      carry out a future intention), executive functioning, and intelligence markers as
      predictors of performance in this widely used naturalistic planning task in 56
      children aged 7- to 12-years-old. Measures of planning, prospection, inhibition,
      crystallized intelligence, and fluid intelligence were collected in an individual
      differences study. Regression analyses showed that prospection (rather than
      traditional measures of intelligence or inhibition) predicted planning,
      suggesting that naturalistic planning tasks such as the Zoo Map task may rely on
      future-oriented cognitive processes rather than executive problem solving or
      general knowledge.

PMID- 27049856
TI  - The Current Landscape of US Pediatric Anesthesiologists: Demographic
      Characteristics and Geographic Distribution.
AB  - BACKGROUND: There is no comprehensive database of pediatric anesthesiologists,
      their demographic characteristics, or geographic location in the United States.
      METHODS: We endeavored to create a comprehensive database of pediatric
      anesthesiologists by merging individuals identified as US pediatric
      anesthesiologists by the American Board of Anesthesiology, National Provider
      Identifier registry, Healthgrades.com database, and the Society for Pediatric
      Anesthesia membership list as of November 5, 2015. Professorial rank was accessed
      via the Association of American Medical Colleges and other online sources.
      Descriptive statistics characterized pediatric anesthesiologists' demographics.
      Pediatric anesthesiologists' locations at the city and state level were geocoded
      and mapped with the use of ArcGIS Desktop 10.1 mapping software (Redlands, CA).
      RESULTS: We identified 4048 pediatric anesthesiologists in the United States,
      which is approximately 8.8% of the physician anesthesiology workforce (n =
      46,000). The median age of pediatric anesthesiologists was 49 years
      (interquartile range, 40-57 years), and the majority (56.4%) were men.
      Approximately two-thirds of identified pediatric anesthesiologists were
      subspecialty board certified in pediatric anesthesiology, and 33% of pediatric
      anesthesiologists had an identified academic affiliation. There is substantial
      heterogeneity in the geographic distribution of pediatric anesthesiologists by
      state and US Census Division with urban clustering. CONCLUSIONS: This description
      of pediatric anesthesiologists' demographic characteristics and geographic
      distribution fills an important gap in our understanding of pediatric anesthesia
      systems of care.

PMID- 27049857
TI  - The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and
      Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.
AB  - BACKGROUND: Whether early goal-directed therapy (EGDT) improves outcome in severe
      sepsis and septic shock remains unclear. We performed a meta-analysis of existing
      clinical trials to examine whether EGDT improved outcome in the resuscitation of
      adult sepsis patients compared with control care. METHODS: We searched for
      eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled
      Trials, and Web of Science databases. Studies were eligible if they compared the
      effects of EGDT versus control care on mortality in adult patients with severe
      sepsis and septic shock. Two reviewers extracted data independently. Data
      including mortality, sample size of the patients with severe sepsis and septic
      shock, and resuscitation end points were extracted. Data were analyzed using
      methods recommended by the Cochrane Collaboration Review Manager 4.2 software.
      Random errors were evaluated by trial sequential analysis (TSA). RESULTS: Nine
      studies compared EGDT with control care, and 5202 severe sepsis and septic shock
      patients were included. A nonsignificant trend toward reduction in the longest
      all-cause mortality was observed in the EGDT group compared with control care
      (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However,
      EGDT significantly reduced intensive care unit mortality in severe sepsis and
      septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P
      = 0.0002). TSA indicated lack of firm evidence for a beneficial effect.
      CONCLUSIONS: In this meta-analysis, a nonsignificant trend toward reduction in
      the longest all-cause mortality in patients resuscitated with EGDT was noted.
      However, EGDT significantly reduced intensive care unit mortality in severe
      sepsis and septic shock patients. TSA indicated a lack of firm evidence for the
      results. More powered, randomized controlled trials are needed to determine the
      effects.

PMID- 27049858
TI  - Physicochemical Properties Analysis and Secretome of Aspergillus niger in
      Fermented Rapeseed Meal.
AB  - The nutrient digestibility and feeding value of rapeseed meal (RSM) for non
      ruminant animals is poor due to the presence of anti-nutritional substances such
      as glucosinolate, phytic acid, crude fiber etc. In the present study, a solid
      state fermentation (SSF) using Aspergillus niger was carried out with the purpose
      of improving the nutritional quality of RSM. The chemical composition and
      physicochemical properties of RSM before and after fermentation were compared. To
      further understand possible mechanism of solid state fermentation, the
      composition of extracellular enzymes secreted by Aspergillus niger during
      fermentation was analysed using two-dimentional difference gel electrophoresis
      (2D-DIGE) combined with matrix assisted laser desorption ionization-time of
      flight-mass spectrometer (MALDI-TOF-MS). Results of the present study indicated
      that SSF had significant effects on chemical composition of RSM. The fermented
      rapeseed meal (FRSM) contained more crude protein (CP) and amino acid (AA)
      (except His) than unfermented RSM. Notably, the small peptide in FRSM was 2.26
      time larger than that in unfermented RSM. Concentrations of anti-nutritional
      substrates in FRSM including neutral detergent fiber (NDF), glucosinolates,
      isothiocyanate, oxazolidithione, and phytic acid declined (P < 0.05) by 13.47,
      43.07, 55.64, 44.68 and 86.09%, respectively, compared with unfermented RSM. A.
      niger fermentation disrupted the surface structure, changed macromolecular
      organic compounds, and reduced the protein molecular weights of RSM substrate.
      Total proteins of raw RSM and FRSM were separated and 51 protein spots were
      selected for mass spectrometry according to 2D-DIGE map. In identified proteins,
      there were 15 extracellular hydrolases secreted by A. niger including
      glucoamylase, acid protease, beta-glucanase, arabinofuranosidase, xylanase, and
      phytase. Some antioxidant related enzymes also were identified. These findings
      suggested that A. niger is able to secrete many extracellular degradation enzymes
      (especially lignocellulosic hydrolyzing enzymes, acid proteases and phytase)
      during fermentation of RSM, thus altering chemical composition and
      physicochemical properties of RSM. 

PMID- 27049859
TI  - Adherent Use of Digital Health Trackers Is Associated with Weight Loss.
AB  - We study the association between weight fluctuation and activity tracking in an
      on-line population of thousands of individuals using digital health trackers
      (1,749 <= N <= 14,411, depending on the activity tracker considered) with
      millions of recorded activities (119,292 <= N <= 2,221,382) over the years 2013
      2015. In a first between-subject analysis, we found a positive association
      between activity tracking frequency and weight loss. Users who log food with
      moderate frequency lost an additional 0.63% (CI [0.55, 0.72]; p < .001) of their
      body weight per month relative to low frequency loggers. Frequent workout loggers
      lost an additional 0.38% (CI [0.20, 0.56]; p < .001) and frequent weight loggers
      lost an additional 0.40% (CI [0.33, 0.47]; p < .001) as compared to infrequent
      loggers. In a subsequent within-subject analysis on a subset of the population
      (799 <= N <= 6,052) with sufficient longitudinal data, we used fixed effect
      models to explore the temporal relationship between a change in tracking
      adherence and weight change. We found that for the same individual, weight loss
      is significantly higher during periods of high adherence to tracking vs. periods
      of low adherence: +2.74% of body weight lost per month (CI [2.68, 2.81]; p <
      .001) during adherent weight tracking, +1.35% per month (CI [1.26, 1.43]; p <
      .001) during adherent food tracking, and +0.60% per month (CI [0.44, 0.76]; p <
      .001) during adherent workout tracking. The findings suggest that adherence to
      activity tracking can be utilized as a convenient real-time predictor of weight
      fluctuations, enabling large-scale, personalized intervention strategies. 

PMID- 27049860
TI  - A Novel Peptide for Simultaneously Enhanced Treatment of Head and Neck Cancer and
      Mitigation of Oral Mucositis.
AB  - We have characterized a novel 21 amino acid-peptide derived from Antrum Mucosal
      Protein (AMP)-18 that mediates growth promotion of cultured normal epithelial
      cells and mitigates radiation-induced oral mucositis in animal models, while
      suppressing in vitro function of cancer cells. The objective of this study was to
      evaluate these dual potential therapeutic effects of AMP peptide in a clinically
      relevant animal model of head and neck cancer (HNC) by simultaneously assessing
      its effect on tumor growth and radiation-induced oral mucositis in an orthotopic
      model of HNC. Bioluminescent SCC-25 HNC cells were injected into the anterior
      tongue and tumors that formed were then subjected to focal radiation treatment.
      Tumor size was assessed using an in vivo imaging system, and the extent of oral
      mucositis was compared between animals treated with AMP peptide or vehicle
      (controls). Synergism between AMP peptide and radiation therapy was suggested by
      the finding that tumors in the AMP peptide/radiation therapy cohort demonstrated
      inhibited growth vs. radiation therapy-only treated tumors, while AMP peptide
      treatment delayed the onset and reduced the severity of radiation therapy-induced
      oral mucositis. A differential effect on apoptosis appears to be one mechanism by
      which AMP-18 can stimulate growth and repair of injured mucosal epithelial cells
      while inhibiting proliferation of HNC cells. RNA microarray analysis identified
      pathways that are differentially targeted by AMP-18 in HNC vs. nontransformed
      cells. These observations confirm the notion that normal cells and tumor cells
      may respond differently to common biological stimuli, and that leveraging this
      finding in the case of AMP-18 may provide a clinically relevant opportunity. 

PMID- 27049861
TI  - Correction: Exonic Splicing Mutations Are More Prevalent than Currently Estimated
      and Can Be Predicted by Using In Silico Tools.

PMID- 27049862
TI  - Ani s 11-Like Protein Is a Pepsin- and Heat-Resistant Major Allergen of Anisakis
      spp. and a Valuable Tool for Anisakis Allergy Component-Resolved Diagnosis.
AB  - BACKGROUND: Anisakis simplex is a fish parasite responsible for gastrointestinal
      and allergic symptoms in humans. The Ani s 11-like protein has been proposed as
      an Anisakis allergen because its primary structure is similar to that of Ani s
      11. The aims of this work were to analyse the frequency of detection of the Ani s
      11-like protein and assess its diagnostic value. METHODS: rAni s 11-like protein,
      rAni s 5 and rAni s 4 were expressed in Escherichia coli and rAni s 1 was
      produced in Pichia pastoris. Recombinant allergen detection patterns in 37
      Anisakis-sensitised patients were determined. The stability to pepsin digestion
      and heat treatment of rAni s 11-like protein was also analysed by IgE
      immunoblotting. RESULTS: Ani s 11-like protein is a major allergen detected by
      78% of Anisakis-allergic patients, and 13.5% of patients detect only the rAni s
      11-like allergen. This allergen is heat stable because it retains its capability
      of binding IgE after boiling for 30 min and it is resistant to pepsin digestion
      for 120 min. CONCLUSIONS: These data indicate that the Ani s 11-like protein is a
      pepsin- and heat-resistant major allergen (Ani s 11.0201) of Anisakis spp. and a
      valuable tool for Anisakis allergy component-resolved diagnosis.

PMID- 27049863
TI  - The biopsychosocial benefits and shortfalls for armed forces veterans engaged in
      archaeological activities.
AB  - BACKGROUND: Organised outdoor activities are advocated as promoting multiple
      benefits for a veteran's wellbeing, of whom up to 50% have suffered either/both
      physical and mental health (MH) problems. This has resulted in significant
      investment in a growing number of outdoor events, one of which is the Defence
      Archaeology Group (DAG) which utilises the technical and social aspects of field
      archaeology in the recovery and skill development of injured veterans. OBJECTIVE:
      To advance knowledge within veterans' MH and wellbeing through an understanding
      of the potential long term biopsychosocial benefits and shortfalls for veterans
      undertaking DAG activities. DESIGN: A constructivist grounded theory approach was
      used to enable identification of the issues from the participant veteran's
      perspective. SETTING: DAG archaeological excavations in April and August 2015.
      METHOD: Semi-structured interviews with 14 veterans. RESULTS: The qualitative
      coding resulted in the indication of 18 categories subsumed within four clusters:
      motivation and access; mental health; veteran and teamwork; therapeutic
      environment and leadership. DISCUSSION: The psychological benefits were improved
      self-esteem, confidence, a reduction in stigma and motivation to seek help. The
      reduction in situational stressors associated with difficult life conditions also
      appeared to improve mood, and there was a clear benefit in being in a caring
      environment where other people actively paid an interest. There were extended
      social benefits associated with being accepted as part of a team within a
      familiar military environment, which presented an opportunity to establish
      friendships and utilise military skill sets. CONCLUSION: Organised outdoor
      activities offer multi-factorial hope for veterans searching for ways to ease the
      transition to civilian life and recover from military stress and trauma. The
      relaxing and reflective environment within a military setting appears to
      construct a sense of personal safety and thereby offers therapeutic value.

PMID- 27049864
TI  - The experience of emotional wellbeing for patients with physical injury: A
      qualitative follow-up study.
AB  - INTRODUCTION: Traumatic physical injury is abrupt, painful, debilitating, costly
      and life-altering. The experience of emotional wellbeing following traumatic
      physical injury has not been well investigated, and the role of health services
      and how services can support the emotional recovery of injured patients has not
      been well understood. This has impacted on care provision and contributed to a
      lack of evidence-informed guidance for clinicians to support patients' emotional
      wellbeing. AIM: To explore the patient experience of emotional wellbeing
      following injury and to understand how injured patients manage their emotional
      wellbeing. METHOD: The study comprises the follow-up qualitative phase of a mixed
      methods explanatory sequential study. Semi-structured interviews were conducted
      with a purposive sample of 14 participants admitted to hospital following
      physical injury. Participants were purposely selected where they had reported
      high levels of depression, anxiety and stress on the DASS-21 at 3 and 6-months
      after injury. The qualitative data were analysed using thematic analysis.
      RESULTS: Three main themes were identified: experiencing the many impacts of
      injury; facing the emotional journey following injury; and being supported and
      managing the impacts of injury. Key findings were the extreme negative emotional
      responses experienced many months after the injury; a strong physical link
      between the emotional and physical aspects of health; participant reluctance to
      seek emotional support; a lack of emotional support provision by the health
      service and a subsequent need for individual and group support in order to
      develop resilience in the injured person. Finally, male participants who reported
      extreme emotional responses after injury, including suicidality, were less likely
      to seek help for their symptoms. CONCLUSION: Injured patients can experience
      substantial negative emotional responses following injury. The lack of support
      provided by health services to injured patients identified highlights the
      importance of in-hospital screening for emotional wellbeing and follow-up post
      discharge, and a support network for patients to reduce the negative impacts of
      injury on their mental health. There is a need for anticipatory guidance
      frameworks for clinicians.

PMID- 27049865
TI  - Varicose Vein or Non-Varicose Vein: That is the Question.

PMID- 27049866
TI  - Highly selective, sensitive and fast-responsive fluorescent sensor for Hg(2+).
AB  - A phenylamine-oligothiophene-based fluorescent sensor 2TBEA was reported. This
      sensor exhibited highly selective, sensitive and rapid detection of Hg(2+) ion in
      THF/H2O (7/3, v/v) solution through fluorescence quenching. The detection was
      unaffected by the coexistence of other competitive metal cations including Na(+),
      K(+), Ag(+), Ca(2+), Fe(3+), Al(3+), Co(2+), Cu(2+), Ni(2+), Zn(2+), Pb(2+),
      Cd(2+), Fe(2+) and Cr(3+). A1:1 binding ratio for 2TBEA - Hg(2+) was demonstrated
      by Job's plot and mole-ratio curves. The coordination process was chemically
      reversible with EDTA. The detection limit was evaluated to be as low as 6.164*10(
      8)M. 

PMID- 27049867
TI  - Spectroscopic studies and molecular docking on the interaction of organotin
      antitumor compound bis[2,4-difluoro-N-(hydroxy-?kappa?O)benzamidato
      ?kappa?O]diphenyltin(IV) with human cytochrome P450 3A4 protease.
AB  - A novel organotin DFDPT was synthesized and characterized by elemental analysis,
      IR, (1)H, (13)C, (119)Sn, NMR techniques,etc. In order to investigate profoundly
      the relationship between DFDPT with human CYP3A4 proteaset and anticancer
      molecular mechanism of DFDPT, the intercalative mode of binding of DFDPT with
      CYP3A4 under physiological conditions were comprehensively evaluated using steady
      state, synchronous, three-dimensional fluorescence spectroscopy,circular
      dichroism and molecular docking. Fluorescence emission data showed that CYP3A4
      fluorescence affected by DFDPT was a static quenching procedure, which implied
      that DFDPT-CYP3A4 complex had been formed. Apparent binding constants Kb of
      CYP3A4 with compound at 298 and 310K were 2.51*10(7) and 3.09*10(5),
      respectively. The binding sites number n was 1.64 and 1.22, respectively. The
      thermodynamic parameters DeltaH and DeltaS of the DFDPT-CYP3A4 complex were
      negative, which indicated that their interaction was driven mainly by hydrogen
      bonding and van der Waals force. The binding of DFDPT-CYP3A4 was spontaneous
      process in which DeltaG was negative. The synchronous results showed DFDPT
      induced conformational changes of CYP3A4 protein. Three-dimensional fluorescence
      and circular dichroism spectra results also revealed conformation of CYP3A4
      protein had been possible changed in the presence of DFDPT. Molecular docking was
      used to study the interaction orientation between DFDPT and CYP3A4 protease. The
      results indicated that DFDPT interacted with a panel of amino acids in the active
      sites of CYP3A4 protein mainly through formation of hydrogen bond. Furthermore,
      the predicted binding mode of DFDPT into CYP3A4 appeared to adopt an orientation
      with interactions among Arg105, Ser119 and Thr309. 

PMID- 27049868
TI  - Transformation of toxic and allelopathic lantana into a benign organic fertilizer
      through vermicomposting.
AB  - In a first study of its kind, the composition of vermicompost derived solely from
      the toxic and allelopathic weed lantana has been investigated using UV-visible
      and Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric (TG) and
      differential scanning calorimetry (DSC), gas chromatography-mass spectometry (GC
      MS), and scanning electron microscopy (SEM). The studies reveal that a sharp
      reduction in humification index, substantial mineralization of organic matter and
      degradation of complex aromatics such as lignin and polyphenols into simpler
      carbohydrates and lipids occur in the course of vermicomposting. GC-MS analysis
      shows significant fragmentation, bio-oxidation and molecular rearrangements of
      chemical compounds in vermicompost in comparison to those in lantana. SEM
      micrographs of vermicompost reflect strong disaggregation of material compared to
      the much better formed lantana matrices. The phenols and sesquiterpene lactones
      which are specifically responsible for the toxicity and allelopathy of lantana
      are seen to get significantly degraded in the course of vermicomposting - turning
      it into a plant-friendly organic fertilizer. The study leads to the possibility
      that the millions of tons of phytomass that is generated annually by lantana can
      be gainfully utilized in producing organic fertilizer via vermicomposting. 

PMID- 27049869
TI  - Burkholderia novacaledonica sp. nov. and B. ultramafica sp. nov. isolated from
      roots of Costularia spp. pioneer plants of ultramafic soils in New Caledonia.
AB  - The taxonomic status of eleven rhizospheric bacterial strains belonging to the
      genus Burkholderia and isolated from roots of Costularia (Cyperaceae), tropical
      herbaceous pioneer plants growing on ultramafic soils in New Caledonia, was
      investigated using a polyphasic taxonomic approach. The genetic analyses (16S
      rRNA genes, gyrB, recA, nreB and cnr) confirmed that all strains are Burkholderia
      and cluster into two separated groups. The DNA hybridization results showed low
      relatedness values to the closest relatives Burkholderia species. The phenotypic
      analyses confirmed that the two groups of strains could be differentiated from
      each other and from other known Burkholderia species. This polyphasic study
      revealed that these two groups of strains represent each a novel species of
      Burkholderia, for which the names Burkholderia novacaledonica sp. nov. (type
      strain STM10272(T)=LMG28615(T)=CIP110887(T)) and B. ultramafica sp. nov. (type
      strain STM10279(T)=LMG28614(T)=CIP110886(T)) are proposed, respectively. These
      strains of Burkholderia presented specific ecological traits such as the
      tolerance to the extreme edaphic constraints of ultramafic soils: they grew at pH
      between 4 and 8 and tolerate the strong unbalanced Ca/Mg ratio (1/19) and the
      high concentrations of heavy metals i.e. Co, Cr, Mn and Ni. Noteworthy B.
      ultramafica tolerated nickel until 10mM and B. novacaledonica up to 5mM. The
      presence of the nickel (nreB) and cobalt/nickel (cnr) resistance determinants
      encoding for protein involved in metal tolerance was found in all strains of both
      groups. Moreover, most of the strains were able to produce plant growth promoting
      molecules (ACC, IAA, NH3 and siderophores). Such ecological traits suggest that
      these new species of Burkholderia might be environmentally adaptable plant
      associated bacteria and beneficial to plants. 

PMID- 27049870
TI  - Suppression of connective tissue growth factor mediates the renoprotective effect
      of Sitagliptin rather than Pioglitazone in type 2 diabetes mellitus.
AB  - AIM: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and
      thus, the ability of antidiabetic drugs to ameliorate renal microvascular disease
      may be as important as their ability to control blood glucose. Therefore, we
      investigated the reno-protective effect of the antidiabetic drugs, Sitagliptin
      and Pioglitazone, versus combined Metformin/Enalapril in a rat model of type 2
      diabetes. METHOD: Male Wistar rats were randomly assigned to be either normal
      control or diabetic. Induction of type 2 diabetes was done by intraperitoneal
      injection of? low dose streptozotocin (35mg/kg) on top of 2 weeks of high fat
      diet. Hyperglycemic animals were divided into 4 groups: untreated diabetic,
      Sitagliptin (10mg/kg), Pioglitazone (10mg/kg) and Metformin/Enalapril (500,
      10mg/kg, respectively) treated. After 6 weeks, fasting blood glucose, plasma
      insulin, beta-cell function, insulin resistance, serum lipids, urea & creatinine,
      albuminurea, kidney weight, renal oxidative stress, plasma connective tissue
      growth factor (CTGF) and renal histopathology were assessed. KEY FINDINGS:
      Sitagliptin decreased microalbuminurea, urea & creatinine, renal tropism,
      oxidative stress and CTGF to levels similar to Metformin/Enalapril group. It also
      preserved near normal renal histology. Although Pioglitazone treatment reduced
      urea, creatinine, renal tropism and oxidative stress, it did not improve renal
      pathological changes or significantly alter CTCF. SIGNIFICANCE: Early Sitagliptin
      treatment in type 2 diabetes can equally ameliorate renal functions and
      structural changes as combined Metformin/Enalapril. Moreover Sitagliptin is a
      better renoprotective than Pioglitazone, probably due to its suppressor effect on
      CTGF, a key factor mediating diabetic renal injury.

PMID- 27049872
TI  - [Draft of a Royal Decree which regulates the manufacture, presentation and sale
      of tobacco and related products].

PMID- 27049871
TI  - Endothelin receptor antagonists in sickle cell disease: A promising new
      therapeutic approach.
AB  - Sickle cell disease (SCD) is a genetic hematologic disorder that is characterized
      by a variety of potentially life threatening acute and chronic complications.
      Currently, hydroxyurea is the only clinically approved pharmacological therapy
      for the treatment of SCD, and the continued prevalence of severe disease
      complications underscores the desperate need for the development of new
      therapeutic agents. Central features of the sickle cell disease milieu, including
      hypoxia, oxidative stress, and thrombosis, are established enhancers of
      endothelin-1 (ET-1) synthesis. This conceptual connection between ET-1 and SCD
      was confirmed by multiple studies that demonstrated markedly elevated plasma and
      urinary levels of ET-1 in SCD patients. Direct evidence for the involvement of ET
      1 signaling in the development of SCD pathologies has come from studies using
      endothelin receptor antagonists in SCD mice. This review summarizes recent
      studies that have implicated ET-1 signaling as a mechanistic contributor to
      renal, vascular, pulmonary, and nociceptive complications of sickle cell disease
      and discusses the potential for the use of ET receptor antagonists in the
      treatment of SCD. 

PMID- 27049873
TI  - Bortezomib attenuates palmitic acid-induced ER stress, inflammation and insulin
      resistance in myotubes via AMPK dependent mechanism.
AB  - Bortezomib is an anti-cancer agent that induces ER stress by inhibiting
      proteasomal degradation. However, the effects of bortezomib appear to be
      dependent on its concentration and cellular context. Since ER stress is closely
      related to type 2 diabetes, the authors examined the effects of bortezomib on
      palmitic acid (PA)-induced ER stress in C2C12 murine myotubes. At low
      concentrations (<20nM), bortezomib protected myotubes from PA (750MUM)-induced ER
      stress and inflammation. Either tunicamycin or thapsigargin-induced ER stress was
      also reduced by bortezomib. In addition, reduced glucose uptake and Akt
      phosphorylation induced by PA were prevented by co-treating bortezomib (10nM)
      both in the presence or absence of insulin. These protective effects of
      bortezomib were found to be associated with reduced JNK phosphorylation.
      Furthermore, bortezomib-induced AMPK phosphorylation, and the protective effects
      of bortezomib were diminished by AMPK knockdown, suggesting that AMPK activation
      underlies the effects of bortezomib. The in vivo administration of bortezomib at
      nontoxic levels (at 50 or 200MUg/kg, i.p.) twice weekly for 5weeks to ob/ob mice
      improved insulin resistance, increased AMPK phosphorylation, reduced ER stress
      marker levels, and JNK inhibition in skeletal muscle. The study shows that
      bortezomib reduces ER stress, inflammation, and insulin resistance in vitro and
      in vivo, and suggests that bortezomib has novel applications for the treatment of
      metabolic disorders.

PMID- 27049874
TI  - Clinical Findings and Treatment Outcomes in Patients with Extraprostatic
      Extension Identified on Prostate Biopsy.
AB  - PURPOSE: We describe histopathological, clinical and imaging findings among men
      with extraprostatic extension on prostate biopsy. MATERIALS AND METHODS: We
      searched our institutional pathology database between 2004 and 2015 for pathology
      reports detailing extraprostatic extension on prostate biopsy in untreated
      patients. Patient characteristics, biopsy features, imaging interpretations and
      outcomes were examined. RESULTS: Of 19,950 patients with prostate cancer on
      biopsy 112 had extraprostatic extension for a prevalence of 0.6% (95% CI 0.5
      0.7). Most of the 112 patients had palpable, high grade (Gleason score 9), high
      volume disease, which was classified as high risk in 34 (30%), locally advanced
      in 17 (15%) and metastatic in 39 (35%). Most patients had 1 or 2 cores with
      extraprostatic extension, typically at the base and with concomitant perineural
      invasion. Extraprostatic extension was identified by magnetic resonance imaging
      in 32 of 40 patients (80%). Median followup in those who did not die was 1.3
      years (IQR 0.3-4.2). Outcomes in the subgroup of 24 men treated with radical
      prostatectomy were consistent with high risk disease, including positive margins
      in 14 (58%), seminal vesicle invasion in 10 (42%) and lymph node invasion in 11
      (46%). In the entire cohort the 3-year risks of metastasis and overall mortality
      were 32% (95% CI 22-44) and 37% (95% CI 27-50), respectively. We did not find
      evidence to suggest that the proportion of cores with cancer that also had
      extraprostatic extension was associated with overall mortality (p = 0.09).
      CONCLUSIONS: Extraprostatic extension is a rare finding on prostate biopsy. It is
      strongly associated with other features of aggressive prostate cancer.

PMID- 27049875
TI  - Prospective Evaluation of the Effect of Thigh Dissection for Removal of
      Transobturator Mid Urethral Slings on Refractory Thigh Pain.
AB  - PURPOSE: Transobturator slings have higher rates of de novo neurologic symptoms
      than retropubic slings, most commonly related to the thigh. Cases refractory to
      conservative management may require removal of the thigh portion of the sling. In
      this series we prospectively examine the effect of thigh dissection with mesh
      removal on refractory thigh pain. MATERIALS AND METHODS: All thigh dissections
      for refractory neurologic symptoms after transobturator sling placement were
      followed prospectively from October 2012 to October 2015. Patients were assessed
      preoperatively, with a pain score using a visual analog scale, and
      postoperatively with a global response assessment. RESULTS: A total of 12 thigh
      dissections were performed from October 2012 to October 2015 in 8 patients. Mean
      (+/-SD) time from original mesh placement to presentation was 2.7 (+/-1.5) years.
      Average preoperative pain score was 7.9 (+/-1.7) out of 10, with pain in the
      thigh in all patients. Seven cases involved unilateral thigh dissection and 1 had
      concomitant bilateral thigh dissection. Five patients underwent concurrent
      transvaginal excision. On postoperative evaluation the average global response
      rating was 1.6, with 1 defined as very much better and 2 defined as much better.
      Of the 8 patients 3 went on to have the contralateral side done with an average
      global response rating of 1.3 (+/-0.6). One patient underwent further treatment
      for stress urinary incontinence with placement of a retropubic mid urethral
      sling. CONCLUSIONS: Our prospective series supports the use of thigh dissection
      in patients with refractory neurologic symptoms after transobturator sling
      placement. The procedure can be performed safely with positive outcomes for the
      patient.

PMID- 27049876
TI  - 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species
      Specific Differences in Progenitor Behavior Contributing to Brain Size.
AB  - Variation in cerebral cortex size and complexity is thought to contribute to
      differences in cognitive ability between humans and other animals. Here we
      compare cortical progenitor cell output in humans and three nonhuman primates
      using directed differentiation of pluripotent stem cells (PSCs) in adherent two
      dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal
      lineage analysis showed that primate cortical progenitors proliferate for a
      protracted period of time, during which they generate early-born neurons, in
      contrast to rodents, where this expansion phase largely ceases before
      neurogenesis begins. The extent of this additional cortical progenitor expansion
      differs among primates, leading to differences in the number of neurons generated
      by each progenitor cell. We found that this mechanism for controlling cortical
      size is regulated cell autonomously in culture, suggesting that primate cerebral
      cortex size is regulated at least in part at the level of individual cortical
      progenitor cell clonal output.

PMID- 27049877
TI  - "Doctors are in the best position to know...": The perceived medicalization of
      contraceptive method choice in Ibadan and Kaduna, Nigeria.
AB  - OBJECTIVES: The medicalization and clinic-based distribution of contraceptive
      methods have been criticized as barriers to increasing levels of contraceptive
      use in Nigeria and other settings; however, our understanding of how clients
      themselves perceive the contraceptive method decision-making process is very
      limited. METHODS: Focus group discussions among men and women in Ibadan and
      Kaduna, Nigeria, were used to examine attitudes and norms surrounding
      contraceptive method decision-making in September and October of 2010. RESULTS:
      Choosing a family planning method was presented as a medical decision: best done
      by a doctor who conducts clinical tests on the client to determine the best, side
      effect free, contraceptive method for each client. An absolute trust in health
      professionals, hospitals, and governments to provide safe contraception was
      evident. CONCLUSION: The level of medicalization placed on contraceptive method
      choice by urban Nigerians is problematic, especially since a test that can
      determine what contraceptive methods will cause side effects in an individual
      does not exist, and side effects often do occur with contraceptive method use.
      PRACTICE IMPLICATIONS: Provider and client education approaches would help to
      improve client involvement in contraceptive decision-making and method choice.

PMID- 27049878
TI  - The effectiveness of unitization in mitigating age-related relational learning
      impairments depends on existing cognitive status.
AB  - Binding relations among items in the transverse patterning (TP) task is dependent
      on the integrity of the hippocampus and its extended network. Older adults have
      impaired TP learning, corresponding to age-related reductions in hippocampal
      volumes. Unitization is a training strategy that can mitigate TP impairments in
      amnesia by reducing reliance on hippocampal-dependent relational binding and
      increasing reliance on fused representations. Here we examined whether healthy
      older adults and those showing early signs of cognitive decline would also
      benefit from unitization. Although both groups of older adults had
      neuropsychological performance within the healthy range, their TP learning
      differed both under standard and unitized training conditions. Healthy older
      adults with impaired TP learning under standard training benefited from unitized
      training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed
      greater impairments under standard conditions, and showed no evidence of
      improvement with unitization. These individuals' failures to benefit from
      unitization may be a consequence of early deficits not seen in older adults who
      pass the MoCA.

PMID- 27049879
TI  - Comparison of the effects of virtual reality-based balance exercises and
      conventional exercises on balance and fall risk in older adults living in nursing
      homes in Turkey.
AB  - OBJECTIVES: There is limited information on effective balance training techniques
      including virtual reality (VR)-based balance exercises in residential settings
      and no studies have been designed to compare the effects of VR-based balance
      exercises with conventional balance exercises in older adults living in nursing
      homes in Turkey. The objective of our study was to investigate the effects of VR
      based balance exercises on balance and fall risk in comparison to conventional
      balance exercises in older adults living in nursing homes. METHODS: A total
      sample of 18 subjects (65-82 years of age) with fall history who were randomly
      assigned to either the VR group (Group 1, n = 7) or the conventional exercise
      group (Group 2, n = 11) completed the exercise training. RESULTS: In both groups,
      Berg balance score (BBS), timed up & go duration, and left leg stance and tandem
      stance duration with eyes closed significantly improved with time (p < 0.05), but
      changes were similar in both groups (p > 0.05) after training, indicating that
      neither the exercise method was superior. CONCLUSION: Similar improvements were
      found in balance and fall risk with VR-based balance training and conventional
      balance training in older adults living in the nursing home. Both exercise
      trainings can be preferable by health care professionals considering fall
      prevention. Appropriate patient selection is essential.

PMID- 27049880
TI  - Response to: Functional neuroimaging and diagnostic reasoning.

PMID- 27049881
TI  - Low-Level Blast Exposure Increases Transient Receptor Potential Vanilloid 1
      (TRPV1) Expression in the Rat Cornea.
AB  - BACKGROUND: Blast-related ocular injuries sustained by military personnel have
      led to rigorous efforts to elucidate the effects of blast exposure on
      neurosensory function. Recent studies have provided some insight into cognitive
      and visual deficits sustained following blast exposure; however, limited data are
      available on the effects of blast on pain and inflammatory processes.
      Investigation of these secondary effects of blast exposure is necessary to fully
      comprehend the complex pathophysiology of blast-related injuries. The overall
      purpose of this study is to determine the effects of single and repeated blast
      exposure on pain and inflammatory mediators in ocular tissues. METHODS: A
      compressed air shock tube was used to deliver a single or repeated blast (68.0 +/
      2.7 kPa) to anesthetized rats daily for 5 days. Immunohistochemistry was
      performed on ocular tissues to determine the expression of the transient receptor
      potential vanilloid 1 (TRPV1) channel, calcitonin gene-related peptide (CGRP),
      substance P (SP), and endothelin-1 (ET-1) following single and repeated blast
      exposure. Neutrophil infiltration and myeloperoxidase (MPO) expression were also
      assessed in blast tissues via immunohistochemistry and enzyme-linked
      immunosorbent assay (ELISA) analysis, respectively. RESULTS: TRPV1 expression was
      increased in rat corneas exposed to both single and repeated blast. Increased
      secretion of CGRP, SP, and ET-1 was also detected in rat corneas as compared to
      control. Moreover, repeated blast exposure resulted in neutrophil infiltration in
      the cornea and stromal layer as compared to control animals. CONCLUSION: Single
      and repeated blast exposure resulted in increased expression of TRPV1, CGRP, SP,
      and ET-1 as well as neutrophil infiltration. Collectively, these findings provide
      novel insight into the activation of pain and inflammation signaling mediators
      following blast exposure.

PMID- 27049891
TI  - Psychometric testing of the Norwegian version of the Expanded Prostate Cancer
      Index Composite 26-item version (EPIC-26).
AB  - OBJECTIVES: In patients with prostate cancer, evaluation of quality of care
      requires the inclusion of patient-reported outcomes measures assessed by
      validated and reliable instruments. Basic psychometric tests of the Norwegian
      version of the Expanded Prostate Cancer Index Composite with 26 items (EPIC-26)
      were performed in this study. MATERIAL AND METHODS: Translation of the original
      questionnaire (University of California, Los Angeles Prostate Cancer Index
      Composite), field testing and retranslation were done according to published
      guidelines. The final EPIC-26 items were subsequently selected from the Norwegian
      version of the EPIC-50 with slight verbal adjustments to comply with the English
      version of the EPIC-26. Reliability and validity were tested among 471 patients
      who, between 2009 and 2010, had been included in a prospective Norwegian
      multicenter study assessing adverse effects after radical prostatectomy or
      prostatic radiotherapy, usually combined with (neo)adjuvant hormone treatment.
      All patients completed the EPIC-26 before treatment and 3 and 12 months
      afterwards. RESULTS: Internal consistency was documented by Cronbach's alpha
      coefficients ranging from 0.64 to 0.91 for the five domains/subdomains. Item-to
      scale correlation coefficients ranged from 0.20 to 0.88, with the lowest value
      (0.20) for overall sexual problem. Criterion validity was proven by significant
      correlations between individual responses to the International Prostate Symptom
      Score and sum scores of the irritative/obstructive subdomain score of the EPIC
      26. Satisfactory sensitivity and responsiveness reflected clinical utility for
      assessing between-group differences and treatment-related changes. CONCLUSIONS:
      Based on basic psychometric tests, the Norwegian version of the EPIC-26 showed
      acceptable reliability and validity for assessment of adverse effects after
      treatment of non-metastatic prostate cancer.

PMID- 27049892
TI  - Exploring Factor Model Parameters across Continuous Variables with Local
      Structural Equation Models.
AB  - Using an empirical data set, we investigated variation in factor model parameters
      across a continuous moderator variable and demonstrated three modeling
      approaches: multiple-group mean and covariance structure (MGMCS) analyses, local
      structural equation modeling (LSEM), and moderated factor analysis (MFA). We
      focused on how to study variation in factor model parameters as a function of
      continuous variables such as age, socioeconomic status, ability levels,
      acculturation, and so forth. Specifically, we formalized the LSEM approach in
      detail as compared with previous work and investigated its statistical properties
      with an analytical derivation and a simulation study. We also provide code for
      the easy implementation of LSEM. The illustration of methods was based on cross
      sectional cognitive ability data from individuals ranging in age from 4 to 23
      years. Variations in factor loadings across age were examined with regard to the
      age differentiation hypothesis. LSEM and MFA converged with respect to the
      conclusions. When there was a broad age range within groups and varying relations
      between the indicator variables and the common factor across age, MGMCS produced
      distorted parameter estimates. We discuss the pros of LSEM compared with MFA and
      recommend using the two tools as complementary approaches for investigating
      moderation in factor model parameters. 

PMID- 27049893
TI  - Topical calcineurin inhibitors in eczema and cancer association: A cohort study.
AB  - INTRODUCTION: Cancer risk associated with topical calcineurin inhibitors (TCIs)
      remains unclear. OBJECTIVE: To evaluate the association between TCIs and cancer
      among patients with atopic and endogenous eczema. METHODS: Incident cancers were
      identified from the National Cancer Registry. Data were analyzed using the Cox
      proportional hazards model to estimate hazard ratios (HRs) and 95% confidence
      intervals. RESULTS: 880 unique cases of cancer developed in 66 176 patients from
      2004 to 2012. The adjusted HRs for overall malignancy were 0.82 (95%CI 0.44-1.39)
      for tacrolimus-exposed and 1.30 (95%CI 0.59-2.45) for pimecrolimus-exposed. The
      only significant cancer association observed was lymphoid leukemia among the
      tacrolimus-exposed: HR 7.58 (95%CI 1.64-25.8). All affected patients had young
      onset B-cell leukemia. Subgroup analysis of pediatric patients (<=16 years)
      showed significant association between tacrolimus use and B-cell leukemia: HR
      26.4 (95%CI 4.77-146). CONCLUSIONS: In this first Asian study on the risk of TCIs
      and malignancies, we do not find an association between use of tacrolimus and
      pimecrolimus in atopic and endogenous eczema and the overall development of
      malignancies. However, the use of topical tacrolimus was found to be associated
      with the development of B-cell acute lymphoid leukemia in pediatric eczema
      patients; further studies are required to investigate if a true association
      indeed occurs.

PMID- 27049894
TI  - Validity of WebCAAFE questionnaire for assessment of schoolchildren's dietary
      compliance with Brazilian Food Guidelines.
AB  - OBJECTIVE: To estimate reporting bias of WebCAAFE, a web-based questionnaire for
      the assessment of food intake (recall of frequency of intake of thirty-two food
      items the day before) and physical activity in schoolchildren. DESIGN: Cross
      sectional study. Self-reported food intake on WebCAAFE was compared with direct
      observation of school meals in five public schools. Additional data included
      school grade, sex, BMI, socio-economic status and access to Internet at home.
      Poisson regression was used to calculate the reporting bias (WebCAAFE v. direct
      observation) and the sample size necessary to detect a statistically significant
      difference between WebCAAFE reports and at least 75 % compliance with the
      recommendations for a healthy diet. SETTING: Intentional sample of five
      elementary public schools in Florianopolis, Brazil. SUBJECTS: Schoolchildren (n
      629) from 2nd to 5th grades. RESULTS: Moderate bias magnitude was found for most
      food groups of interest. Frequency of consumption was not related to the bias.
      Sample sizes necessary to detect the compliance with dietary recommendations
      varied between four and seventy-four individuals for the different groups
      investigated. CONCLUSIONS: After adjusting for moderate bias, WebCAAFE may be
      used as a food questionnaire for evaluation of schoolchildren's food compliance
      on a group level, even with a relatively small sample size.

PMID- 27049895
TI  - Fatigue in football: it's not a brainless task!

PMID- 27049896
TI  - EBV-negative aggressive B-cell lymphomas of donor origin after allogeneic
      hematopoietic stem cell transplantation: a report of three cases.
AB  - Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of
      iatrogenic immunosuppression, and the majority is associated with EBV. PTLD after
      allogeneic hematopoietic stem cell transplantation (allo-HCT) are rare. Most
      cases are donor-derived, reflecting immune reconstitution by malignant
      transformed donor cells, and are EBV-positive. We report three unusual cases of
      aggressive EBV-negative PTLD of monomorphic type after allo-HCT. All cases were
      of donor origin and arose with long latency, 4-12 years after HCT. The patients
      had a history of severe graft-versus-host disease (GVHD) resulting in prolonged
      immunosuppression before the diagnosis of lymphoma. In one case, the temporal
      evolution of the malignant clone was analyzed by clone-specific PCR targeting the
      immunoglobulin heavy chain rearrangement. A tumor-specific product was already
      detected 3 years before lymphoma development. This indicates that chronic
      antigenic stimulation and reduced immune surveillance, may promote the outgrowth
      of premalignant donor-derived clones after acquisition of additional genetic
      alterations.

PMID- 27049897
TI  - More data, less information? Potential for nonmonotonic information growth using
      GEE.
AB  - Statistical intuition suggests that increasing the total number of observations
      available for analysis should increase the precision with which parameters can be
      estimated. Such monotonic growth of statistical information is of particular
      importance when data are analyzed sequentially, such as in confirmatory clinical
      trials. However, monotonic information growth is not always guaranteed, even when
      using a valid, but inefficient estimator. In this article, we demonstrate the
      theoretical possibility of nonmonotonic information growth when using generalized
      estimating equations (GEE) to estimate a slope and provide intuition for why this
      possibility exists. We use theoretical and simulation-based results to
      characterize situations that may result in nonmonotonic information growth.
      Nonmonotonic information growth is most likely to occur when (1) accrual is fast
      relative to follow-up on each individual, (2) correlation among measurements from
      the same individual is high, and (3) measurements are becoming more variable
      further from randomization. In situations that may lead to nonmonotonic
      information growth, study designers should plan interim analyses to avoid
      situations most likely to result in nonmonotonic information growth.

PMID- 27049899
TI  - Editorial: The Complex Construct of Mild Cognitive Impairment: Be Aware of
      Cognitive Frailty.

PMID- 27049898
TI  - FPGA-based RF interference reduction techniques for simultaneous PET-MRI.
AB  - The combination of positron emission tomography (PET) and magnetic resonance
      imaging (MRI) as a multi-modal imaging technique is considered very promising and
      powerful with regard to in vivo disease progression examination, therapy response
      monitoring and drug development. However, PET-MRI system design enabling
      simultaneous operation with unaffected intrinsic performance of both modalities
      is challenging. As one of the major issues, both the PET detectors and the MRI
      radio-frequency (RF) subsystem are exposed to electromagnetic (EM) interference,
      which may lead to PET and MRI signal-to-noise ratio (SNR) deteriorations. Early
      digitization of electronic PET signals within the MRI bore helps to preserve PET
      SNR, but occurs at the expense of increased amount of PET electronics inside the
      MRI and associated RF field emissions. This raises the likelihood of PET-related
      MRI interference by coupling into the MRI RF coil unwanted spurious signals
      considered as RF noise, as it degrades MRI SNR and results in MR image artefacts.
      RF shielding of PET detectors is a commonly used technique to reduce PET-related
      RF interferences, but can introduce eddy-current-related MRI disturbances and
      hinder the highest system integration. In this paper, we present RF interference
      reduction methods which rely on EM field coupling-decoupling principles of RF
      receive coils rather than suppressing emitted fields. By modifying clock
      frequencies and changing clock phase relations of digital circuits, the resulting
      RF field emission is optimised with regard to a lower field coupling into the MRI
      RF coil, thereby increasing the RF silence of PET detectors. Our methods are
      demonstrated by performing FPGA-based clock frequency and phase shifting of
      digital silicon photo-multipliers (dSiPMs) used in the PET modules of our MR
      compatible Hyperion II (D) PET insert. We present simulations and magnetic-field
      map scans visualising the impact of altered clock phase pattern on the spatial RF
      field distribution, followed by MRI noise and SNR scans performed with an
      operating PET module using different clock frequencies and phase patterns. The
      methods were implemented via firmware design changes without any hardware
      modifications. This introduces new means of flexibility by enabling adaptive RF
      interference reduction optimisations in the field, e.g. when using a PET insert
      with different MRI systems or when different MRI RF coil types are to be operated
      with the same PET detector. 

PMID- 27049900
TI  - Molecular Crossroads of Frailty and HIV.
AB  - An epidemiological transition is occurring regarding Human Immunodeficiency Virus
      (HIV) infection. This phenomenon, explained by several mechanisms (e.g.:
      physiologic changes, pharmacologic advances, sexual behaviors), is demonstrated
      by a significant increase in the number of patients aged 50 years and older
      diagnosed with this infection. The immunological changes observed in HIV-infected
      patients may prompt the appearance of an accelerated aging process as well as
      that of comorbidities and other pathological entities commonly diagnosed in older
      adults. Frailty is a biologic syndrome characterized by a multi-systemic decrease
      of the individual's physiologic and homeostatic reserves, leading to diminished
      resistance against stressors and increased vulnerability. The purpose of this
      review is to describe the common molecular changes seen in both frailty and HIV-1
      infection, offering an in-depth analysis of their pathophysiology and specifying
      common processes where their pathways meet. 

PMID- 27049901
TI  - Presbyphagia and Sarcopenic Dysphagia: Association between Aging, Sarcopenia, and
      Deglutition Disorders.
AB  - Presbyphagia refers to age-related changes in the swallowing mechanism in the
      elderly associated with a frailty in swallowing. Presbyphagia is different from
      dysphagia. Sarcopenic dysphagia is difficulty swallowing due to sarcopenia of
      generalized skeletal muscles and swallowing muscles. Age-related loss of
      swallowing muscle mass becomes evident in the geniohyoid muscle and tongue.
      Elderly subjects with both sarcopenia and dysphagia may have not only disease
      related dysphagia but also sarcopenic dysphagia. In cases of aspiration
      pneumonia, deterioration in activity-, disease-, and nutrition-related sarcopenia
      of generalized skeletal muscles and swallowing muscles may develop into
      sarcopenic dysphagia. Assessment of sarcopenic dysphagia includes evaluation of
      both dysphagia and sarcopenia. The 10-item Eating Assessment Tool (EAT-10) and a
      water test combined with pulse oximetry are useful for dysphagia screening.
      Assessment of the multi-factorial causes of sarcopenia including nutritional
      review is important, because rehabilitation of sarcopenic dysphagia differs
      depending on its etiology. Consensus diagnostic criteria for sarcopenic dysphagia
      were proposed at the 19th Annual Meeting of the Japanese Society of Dysphagia
      Rehabilitation. Rehabilitation for sarcopenic dysphagia includes treatment of
      both dysphagia and sarcopenia. The core components of dysphagia rehabilitation
      are oral health care, rehabilitative techniques, and food modification. The
      causes of adult malnutrition may also contribute to the etiology of secondary
      sarcopenia and sarcopenic dysphagia. Therefore, nutrition management is
      indispensable for sarcopenic dysphagia rehabilitation. In cases of sarcopenia
      with numerous complicating causes, treatment should include pharmaceutical
      therapies for age-related sarcopenia and comorbid chronic diseases, resistance
      training, early ambulation, nutrition management, protein and amino acid
      supplementation, and non-smoking. 

PMID- 27049902
TI  - Association between Self-Reported Health Status and Frailty in Community-Dwelling
      Elderly.
AB  - BACKGROUND: The phenotype of frailty proposed by Fried et al. has been related
      with increased vulnerability for the development of adverse health-related
      outcomes. However, this phenotype is not often used in daily clinical practice.
      On the other hand, poor self-reported health status (SRHS) has been associated
      with similar adverse health-related outcomes. OBJECTIVES: To determine the
      association between poor SRHS and frailty. DESIGN, SETTING AND PARTICIPANTS:
      Cross-sectional study of 927 community-dwelling elderly aged 70 and older,
      participating in the Mexican Study of Nutritional and Psychosocial Markers of
      Frailty. MEASUREMENTS: SRHS was established by the question "How do you rate your
      health status in general?" Frailty was defined according to the phenotype
      proposed by Fried et al. The association between SRHS and frailty was determined
      through the construction of multinomial logistic regression models. Final
      analyses were adjusted by socio-demographic and health covariates, including
      depressive symptoms. Also, agreement between SRHS and the phenotype of frailty
      was explored. RESULTS: Prevalence of frailty was 14.1%, and 4.4% of participants
      rated their health status as "poor". The unadjusted regression analyses
      demonstrated that fair and poor SRHS were significantly associated with prefrail
      and frail status. After adjustment for multiple covariates, the association
      remained statistically significant. However, in the final adjustment for
      depressive symptoms, only the association between poor SRHS and frail status
      continued to be statistically significant. Fair agreement between poor SRHS and
      frail status was also found. CONCLUSION: Poor SRHS shares common correlates as
      well as health-related adverse outcomes with frailty syndrome, and remains
      associated with it even when possible confounders are taken into account.
      Therefore, poor SRHS could be further explored as an option for frailty syndrome
      screening.

PMID- 27049903
TI  - Gait Speed and Handgrip Strength as Predictors of Incident Disability in Mexican
      Older Adults.
AB  - Physical performance tests are associated with different adverse outcomes in
      older people. The objective of this study was to test the association between
      handgrip strength and gait speed with incident disability in community-dwelling,
      well-functioning, Mexican older adults (age >=70 years). Incident disability was
      defined as the onset of any difficulty in basic or instrumental activities of
      daily living. Of a total of 133 participants, 52.6% (n=70) experienced incident
      disability during one year of follow-up. Significant associations of handgrip
      strength (odds ratio [OR] 0.96, 95% confidence interval [95%CI] 0.93-0.99) and
      gait speed (OR 0.27, 95%CI 0.07-0.99) with incident disability were reported. The
      inclusion of covariates in the models reduced the statistical significance of the
      associations without substantially modifying the magnitude of them. Handgrip
      strength and gait speed are independently associated with incident disability in
      Mexican older adults. 

PMID- 27049904
TI  - Stage-Specific Relationship between Frailty and Cognitive Impairment in a
      Specialist Memory Clinic Setting.
AB  - BACKGROUND: It is unclear if the complex relationship between physical frailty
      and cognition varies across the severity of cognitive impairment. OBJECTIVES: We
      therefore aimed to explore if there are stage-specific differences in the
      relationship between frailty and cognitive impairment. DESIGN: Cross-sectional
      study. SETTING: A specialist Memory Clinic setting. PARTICIPANTS: Mild cognitive
      impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling
      subjects. MEASUREMENTS: We obtained data on demographics, multimorbidity,
      cognition-related measures, nutrition, neuroimaging measures, muscle mass,
      Vitamin D level, apolipoprotein - e (APOE) status and physical performance
      measures. Frailty measures of gait speed, hand grip strength, question on
      exhausation and weight loss, classified subjects according to the Buchmann
      criteria into non-frail and frail categories. RESULTS: Forty-five MCI, 64 mild AD
      and 13 moderate AD subjects (total n=122) were studied. The prevalence of frailty
      for MCI, mild AD and moderate AD was 35.6%, 21.9% and 46.2% respectively,
      indicating a u-shaped trend. Significant differences were noted in fatigue, grip
      strength and gait speed frailty sub-items. Significant correlation of frailty
      with cognition were noted in mild-moderate AD (Spearman's coefficient 0.26,
      p<0.05) but not in MCI (0.01, p=0.6). No other differences in multimorbidity,
      Vitamin D, APOE, nutritional measures, white matter lesions were observed.
      Sarcopenia interestingly had an inverse stage-specific relationship unlike
      frailty. CONCLUSIONS: Our results suggest a U-shaped relationship between frailty
      and cognition, characterized by initial dissociation with cognitive impairment
      and subsequent convergence at later stages. Future studies incorporating immune
      markers and endocrine pathways with longitudinal follow-up could potentially
      elucidate intermediary mechanisms in the frailty cascade.

PMID- 27049906
TI  - Predicting the Efficacy of Protein-Energy Supplementation in Frail Older Adults
      Living in Community.
AB  - BACKGROUND: Protein-energy malnutrition is a major cause of functional decline in
      the elderly and is clearly an important component of frailty. However, limited
      evidence is available about how to select frail individuals most benefiting from
      protein-energy supplementation. OBJECTIVES: 1) To investigate factors associated
      with stronger benefits from protein-energy supplementation, and 2) to test the
      hypothesis that the severity of frailty is associated with the efficacy of
      protein-energy supplementation. DESIGN: Secondary analysis of data from a pre
      post-intervention study and a clinical trial. SETTING: National Home Healthcare
      Services in Gangbuk-gu, Seoul, South Korea. PARTICIPANTS: 123 community-dwelling
      frail older adults [usual gait speed (UGS) <0.6m/sec and Mini Nutritional
      Assessment (MNA) <24]. INTERVENTION: Each participant was received with two 200
      mL per day of commercial liquid formula (providing additional 400 kcal of energy
      and 25 g of protein per day) for 12 weeks. MEASUREMENTS: Relative change in the
      Physical Functioning (PF) and Short Physical Performance Battery (SPPB) score
      between the baseline and 12-week follow-up assessments were measured. RESULTS:
      Multilevel mixed-effect linear regression analysis showed that a lower level of
      baseline UGS was associated with a greater improvement in PF and SPPB score after
      adjustment for age, gender, education, living status, beneficiary of public
      assistance, number of chronic diseases, compliance, and type of dataset
      (p<0.001). A lower level of baseline MNA score was associated with greater change
      in PF and SPPB score after adjustment for multiple covariates (p<=0.045).
      Participants with severe frailty (UGS <0.3 m/sec + MNA <17) showed 52.4% and
      44.6% more relevant improvements in PF and SPPB score, respectively, than those
      with mild frailty (UGS 0.3-0.6 m/sec + MNA 17-24) (p<0.001). CONCLUSION: Slower
      UGS and lower MNA score are independently associated with the greater efficacy of
      protein-energy supplementation on functional status.

PMID- 27049905
TI  - Educational Inequalities and Frailty in Spain: What is the Role of Obesity?
AB  - BACKGROUND: Evaluate how obesity is associated with the development of frailty
      among older adults is important. However, few studies have examined the relation
      between obesity and frailty within different educational backgrounds. OBJECTIVES:
      This study aims to investigate the association between educational level and
      frailty and to evaluate whether obesity explains any possible associations among
      Spanish adults. Design, participants and settings: This is a cross-sectional
      study including 2,319 50-years-old and older community-dwelling Spanish adults,
      who participated in the first wave (2004/05) of the Survey of Health, Ageing and
      Retirement in Europe (SHARE). MEASUREMENTS: Educational differences in frailty
      phenotypes -defined by the SHARE's operationalized criterion- and their
      association with obesity -estimated through self-reports of weight and height-
      were evaluated using multinomial logistic regression analyses. RESULTS: Women
      experienced frailty in a larger proportion than men (22.3% vs. 13.3%). After
      adjusting for all confounders, we found a marked educational gradient in frailty,
      where individuals with non-formal education showed increased odds of a frailty
      phenotype than individuals with higher education. Moreover, obesity was
      significantly related to frailty and the effect of obesity is similar at all
      levels of education after testing for interaction effects. Although there is a
      mediation effect of obesity, the educational gradient in frailty is robust to
      controls for obesity. CONCLUSIONS: Our findings suggest a somehow independent
      effect of both educational background and obesity on frailty among Spanish
      individuals. This adds to the evidence of the frailty-obesity association among
      different educational backgrounds, and has implications for future interventions
      leading to reduce health disparities in elders.

PMID- 27049907
TI  - The Acute Effects of Eccentrically-Biased Versus Conventional Weight Training in
      Older Adults: A Randomised Controlled Cross-Over Study.
AB  - BACKGROUND: Whilst resistance training has been proven to convey considerable
      benefits to older people; immediately post-exercise there may be elevated
      transient risks for cardiac events and falls. Objectives and Measurements: We
      assessed the acute effects of eccentrically-biased (EB) and conventional (CONV)
      resistance exercise on: platelet number, activation and granule exocytsosis; and
      mean velocity of centre of pressure displacement (Vm). DESIGN, SETTING,
      PARTICIPANTS AND INTERVENTION: Ten older adults (7 males, 3 females; 69 +/- 4
      years) participated in this randomised controlled cross-over study in which they
      performed EB and CONV training sessions that were matched for total work and a
      control condition. RESULTS: Immediately post-exercise there was a statistically
      significant difference in platelet count between the control condition, in which
      it had declined (pre 224 +/- 35 109/L; post 211 +/- 30 109/L: P < 0.05) and CONV
      in which it had increased (pre 236 +/- 55 109/L; post 242 +/- 51 109/L: P >
      0.05). There was no change in platelet activation and granule exocytsosis or Vm
      following EB and CONV. CONCLUSIONS: Overall, while minor differences between
      regimens were observed, no major adverse effect on parameters of platelet
      function or centre of pressure displacement were observed acutely following
      either regimen. Eccentrically-biased and conventional resistance exercise
      training regimens do not appear to present an elevated acute risk in the context
      of changes to platelet function contributing to a cardiac event or postural
      stability increasing falls risk for apparently healthy older adults.

PMID- 27049908
TI  - Can Tibial Shaft Fractures Bear Weight After Intramedullary Nailing? A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To examine the potential benefits and risks associated with weight
      bearing after intramedullary (IM) nailing of unstable tibial shaft fractures.
      DESIGN: Randomized controlled trial. SETTING: Two New York State level 1 trauma
      centers, one level 2 trauma center, and 1 tertiary care orthopaedic hospital in a
      large urban center in New York City. PATIENTS/PARTICIPANTS: Eighty-eight patients
      with 90 tibial shaft fractures were enrolled. The following were used as
      inclusion criteria: (1) skeletally mature adult patients 18 years of age or
      older, (2) displaced fractures of tibial diaphysis (OTA type 42) treated with
      operative intervention, and (3) radiographs, including injury, operative, and
      completion of follow-up. Sixty-eight patients with 70 tibial shaft fractures
      completed follow-up. INTERVENTION: All patients were treated with locked IM
      nailing. Patients were randomized to 1 of 2 groups: immediate weight-bearing-as
      tolerated (WBAT) or non-weight-bearing for the first 6 postoperative weeks (NWB).
      MAIN OUTCOME MEASURES: Fracture union or treatment failure/revision surgery.
      RESULTS: There was no statistical difference in the observed time to union
      between groups (WBAT = 22.1 +/- 11.7 weeks vs. NWB = 21.3 +/- 9.9 weeks; P =
      0.76). Rates of complications did not statistically differ between groups. No
      fracture loss of reduction leading to malunion was encountered. Short
      Musculoskeletal Function Assessment scores for all domains did not statistically
      differ between groups. CONCLUSIONS: Immediate weight-bearing after IM nailing of
      tibial shaft fractures is safe and is not associated with an increase in adverse
      events or complications. Patients should be allowed to bear weight as tolerated
      after IM nailing of OTA subtype 42-A and 42-B tibial shaft fractures. LEVEL OF
      EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 27049909
TI  - Playing Catch-Up.
AB  - Physicians say new funding and a streamlined state approach to women's health
      could improve access to screenings and family planning services for low-income
      women and girls. But attracting private practice physicians to the programs could
      be challenging.

PMID- 27049910
TI  - Life After Residency.
AB  - Many residents don't receive any formal business training. The University of
      Texas at Austin Dell Medical School created a crash course to teach residents
      some of the business and job-hunting basics they'll need.

PMID- 27049911
TI  - Putting the Meaning in Meaningful Use.
AB  - Physicians and groups have begun mining their electronic health record data to
      improve patient care and to predict which patients will need certain types of
      health care services in the future. 

PMID- 27049912
TI  - Transparency: Disruptive Innovation.
AB  - Get to know the two prestigious speakers TMA has secured to headline the TexMed
      2016 General Session: Marty A. Makary, MD, and Mark G. Dotzour, PhD. 

PMID- 27049913
TI  - Seeking Invalidation.
AB  - Teladoc's lawsuit against the Texas Medical Board claims TMB rules that require
      telemedicine physicians to conduct a physical patient examination to establish a
      proper patient-physician relationship are not immune from an antitrust challenge.

PMID- 27049914
TI  - Quality Made Easier.
AB  - Medicare and private payers' unveiling of the first set of standardized quality
      measures could be a sign they are finally following through on their promise to
      simplify what physicians describe as a deluge of redundant quality metrics in the
      complex web woven by today's pay-for-performance programs.

PMID- 27049915
TI  - Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for
      Treatment-Resistant Depression: A Randomized Clinical Trial.
AB  - IMPORTANCE: Patients with treatment-resistant depression (TRD) do not respond
      sufficiently to several consecutive treatments for major depressive disorder.
      Deep brain stimulation (DBS) is a promising treatment for these patients, but
      presently placebo effects cannot be ruled out. OBJECTIVE: To assess the efficacy
      of DBS of the ventral anterior limb of the internal capsule (vALIC), controlling
      for placebo effects with active and sham stimulation phases. DESIGN, SETTING, AND
      PARTICIPANTS: Twenty-five patients with TRD from 2 hospitals in the Netherlands
      were enrolled between March 22, 2010, and May 8, 2014. Patients first entered a
      52-week open-label trial during which they received bilateral implants of 4
      contact electrodes followed by optimization of DBS until a stable response was
      achieved. A randomized, double-blind, 12-week crossover phase was then conducted
      with patients receiving active treatment followed by sham or vice versa. Response
      and nonresponse to treatment were determined using intention-to-treat analyses.
      INTERVENTIONS: Deep brain stimulation targeted to the vALIC. MAIN OUTCOMES AND
      MEASURES: The change in the investigator-rated score of the 17-item Hamilton
      Depression Rating Scale (HAM-D-17) was the main outcome used in analysis of the
      optimization phase. The primary outcome of the crossover phase was the difference
      in the HAM-D-17 scores between active and sham DBS. The score range of this tool
      is 0 to 52, with higher scores representing more severe symptoms. Patients were
      classified as responders to treatment (>=50% decrease of the HAM-D-17 score
      compared with baseline) and partial responders (>=25 but <50% decrease of the HAM
      D-17 score). RESULTS: Of 25 patients included in the study, 8 (32%) were men; the
      mean (SD) age at inclusion was 53.2 (8.4) years. Mean HAM-D-17 scores decreased
      from 22.2 (95% CI, 20.3-24.1) at baseline to 15.9 (95% CI, 12.3-19.5) (P = .001),
      Montgomery-Asberg Depression Rating Scale scores from 34.0 (95% CI, 31.8-36.3) to
      23.8 (95% CI, 18.4-29.1) (P < .001), and Inventory of Depressive Symptomatology
      Self-report scores from from 49.3 (95% CI, 45.4-53.2) to 38.8 (95% CI, 31.6-46.0)
      (P = .005) in the optimization phase. Following the optimization phase, which
      lasted 51.6 (22.0) weeks, 10 patients (40%) were classified as responders and 15
      individuals (60%) as nonresponders. Sixteen patients entered the randomized
      crossover phase (9 responders [56%], 7 nonresponders [44%]). During active DBS,
      patients scored significantly lower on the HAM-D-17 scale (13.6 [95% CI, 9.8
      17.4]) than during sham DBS (23.1 [95% CI, 20.6-25.6]) (P < .001). Serious
      adverse events included severe nausea during surgery (1 patient), suicide attempt
      (4 patients), and suicidal ideation (2 patients). CONCLUSIONS AND RELEVANCE: Deep
      brain stimulation of the vALIC resulted in a significant decrease of depressive
      symptoms in 10 of 25 patients and was tolerated well. The randomized crossover
      design corroborates that vALIC DBS causes symptom reduction rather than sham.
      TRIAL REGISTRATION: trialregister.nl Identifier: NTR2118.

PMID- 27049916
TI  - Molecular crosstalk between tumour and brain parenchyma instructs
      histopathological features in glioblastoma.
AB  - The histopathological and molecular heterogeneity of glioblastomas represents a
      major obstacle for effective therapies. Glioblastomas do not develop
      autonomously, but evolve in a unique environment that adapts to the growing
      tumour mass and contributes to the malignancy of these neoplasms. Here, we show
      that patient-derived glioblastoma xenografts generated in the mouse brain from
      organotypic spheroids reproducibly give rise to three different histological
      phenotypes: (i) a highly invasive phenotype with an apparent normal brain
      vasculature, (ii) a highly angiogenic phenotype displaying microvascular
      proliferation and necrosis and (iii) an intermediate phenotype combining features
      of invasion and vessel abnormalities. These phenotypic differences were visible
      during early phases of tumour development suggesting an early instructive role of
      tumour cells on the brain parenchyma. Conversely, we found that tumour-instructed
      stromal cells differentially influenced tumour cell proliferation and migration
      in vitro, indicating a reciprocal crosstalk between neoplastic and non-neoplastic
      cells. We did not detect any transdifferentiation of tumour cells into
      endothelial cells. Cell type-specific transcriptomic analysis of tumour and
      endothelial cells revealed a strong phenotype-specific molecular conversion
      between the two cell types, suggesting co-evolution of tumour and endothelial
      cells. Integrative bioinformatic analysis confirmed the reciprocal crosstalk
      between tumour and microenvironment and suggested a key role for TGFbeta1 and
      extracellular matrix proteins as major interaction modules that shape
      glioblastoma progression. These data provide novel insight into tumour-host
      interactions and identify novel stroma-specific targets that may play a role in
      combinatorial treatment strategies against glioblastoma. 

PMID- 27049917
TI  - PDZ binding kinase (PBK) is a theranostic target for nasopharyngeal carcinoma:
      driving tumor growth via ROS signaling and correlating with patient survival.
AB  - Nasopharyngeal carcinoma (NPC) is well known as one of the most common
      malignancies in southern China and Southeast Asia. However, the mechanisms
      underlying NPC progression remain poorly understood. Herein, through overlapping
      the differentially expressed genes from 3 microarray data sets with the human
      kinome, we identified PBK, a serine-threonine kinase, is highly upregulated and
      has not been intensively investigated in NPC. PBK was required for malignant
      phenotypes of NPC, as PBK depletion by RNAi and inhibition by specific inhibitor
      HI-TOPK-032 obviously reduced cell proliferation and xenograft tumor growth in
      mice. Moreover, we determined that targeting PBK could accelerate apoptosis by
      inducing ROS that activates JNK/p38 signaling pathway. In NPC patients, elevated
      PBK expression in primary tumor positively correlated to clinical severity such
      as advanced T stage, high death risk and disease progression, and it could serve
      as an unfavorable independent indicator of overall survival and disease-free
      survival. Altogether, our results indicate that PBK is a novel significant
      regulator of NPC progression and a potential therapeutic target for NPC patients.

PMID- 27049918
TI  - Downregulation of ATOH8 induced by EBV-encoded LMP1 contributes to the malignant
      phenotype of nasopharyngeal carcinoma.
AB  - Mechanism for the malignant phenotype of nasopharyngeal carcinoma (NPC) remains
      poorly understood. Epstein-Barr virus (EBV) consistently appears in nearly all
      malignant NPC patient samples, suggesting the strong etiological link between the
      malignant phenotype and EBV infection. Here we found that the EBV-encoded latent
      membrane protein (LMP1) enhanced cell growth, motility, invasion and xenograft
      tumor growth of NPC. RNA-seq profiling analysis of LMP1-positive NPC patient
      tissues indicated that widespread gene repression contributed to malignant
      phenotype of NPC. The transcription factor binding site (TFBS) enrichment
      analysis indicated a subset of transcription factors including ATOH8, a novel
      transcript factor which belongs to the basic helix-loop-helix (bHLH) gene family
      inversely enriched in promoters of up-regulated genes and down-regulated genes.
      Importantly, the expression of ATOH8 was suppressed in both immortalized normal
      nasopharyngeal epithelial cells (NPEC) and NPC cells with LMP1 overexpression.
      The Real-Time PCR and Western Blot assays indicated that ATOH8 decreased
      expression in NPC cell lines and patient samples. Moreover, by gain- or loss-of
      function assays, we demonstrated that ATOH8 inhibition promoted malignant
      phenotype, whereas ATOH8 restoration reversed malignant phenotype of NPC.
      Finally, we demonstrated that LMP1 inhibited ATOH8 expression by epigenetically
      impairing the occupancy of activating H3K4me3 and enhancing the occupancy of
      repressive H3K27me3 on ATOH8 promoter. Collectively, our study uncovered the
      occurrence of malignant phenotype of NPC induced by EBV infection and
      characterized a novel bHLH transcription factor ATOH8 as a new downstream target
      of LMP1. 

PMID- 27049919
TI  - microRNA-149 targets caspase-2 in glioma progression.
AB  - Malignant gliomas are the most common form of intrinsic primary brain tumors
      worldwide. Alterations in microRNAs play a role in highly invasive malignant
      glioma, but detail mechanism still unknown. In this study, the role and mechanism
      of microRNA-149 (miR-149) in glioma are investigated. We show that miR-149 is
      expressed at substantially higher levels in glioma than in normal tissues. Stable
      overexpression of miR-149 augments potent prosurvival activity, as evidenced by
      promotion of cell viability, inhibition of apoptosis, and induced xenografted
      tumor growth in vivo. We further show that Caspase-2 is identified as a
      functional target of miR-149 and expression of caspase-2 is inversely associated
      with miR-149 in vitro. In addition, miR-149 promotes tumor survival in the U87-MG
      and A172 cell lines and it targets caspase-2 via inactivation of the p53 and p21
      pathways. There results support a special role for miR-149 by targeting Caspase-2
      to impact on p53 signaling pathway. We speculate that miR-149 has distinct
      biological functions in p53 wild type cells and p53 mutation cells, and the
      mechanisms involved remain to be explored in future. Our study suggests that
      targeting miR-149 may be a novel therapy strategy for treating p53 wild type
      glioma tumors in humans. 

PMID- 27049920
TI  - Analysis of disseminated tumor cells before and after platinum based chemotherapy
      in primary ovarian cancer. Do stem cell like cells predict prognosis?
AB  - BACKGROUND: We recently reported that the presence of disseminated tumor cells
      (DTCs) in the bone marrow (BM) of primary ovarian cancer patients (POC pts)
      correlated with reduced progression free survival (PFS) and overall survival
      (OS). Here we analyzed whether the negative prognostic influence was related to
      DTC persistence after platinum based chemotherapy and/or due to DTCs associated
      with stem cell character. RESULTS: DTCs were detected in 33/79 pts (42%) before
      and in 32/79 pts (41%) AT. Persistent DTCs were found in 13 pts, 20 pts were only
      positive BT, 19 pts AT and 27 pts had no DTCs. Whereas the presence of DTCs BT
      significantly correlated with reduced OS (p = 0.02), pts initially DTCneg BT but
      DTCpos AT had a significantly shorter PFS (p = 0.03). DTC persistence resulted in
      a shorter PFS and OS reaching borderline significance (p = 0.06; p = 0.07). LIN
      28-and SOX-2 positive cells were detected in all eight pts AT. PATIENTS AND
      METHODS: 79 POC pts were studied for DTCs before therapy (BT) and after therapy
      (AT) using immunocytochemistry. Eight pts harboring at least five DTCs AT were
      further analyzed on two additional slides by four-fold immunofluorescence
      staining for DAPI, Cytokeratin (CK), SOX-2 or LIN-28, CD45 and CD34 (Cy5). A stem
      like tumor cell was classified as Dapipos, CD45neg, CD34neg, SOX-2pos/LIN-28pos
      and CKpos or CKneg. CONCLUSIONS: Stem cell associated proteins are expressed in
      DTCs that are present AT and their presence seem to be correlated with a worse
      outcome. Additional therapeutic regimens may be necessary to eliminate these
      cells.

PMID- 27049921
TI  - MicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance
      via DAPK2 repression.
AB  - The lack of efficient tumor progression and chemoresistance indicators leads to
      high mortality in epithelial ovarian cancer (EOC) patients. Dysregulated miR-520g
      expression is involved in these processes in hepatic and colorectal cancers. In
      this study, we found that miR-520g expression gradually increased across normal,
      benign, borderline and EOC tissues. High miR-520g expression promoted tumor
      progression and chemoresistance to platinum-based chemotherapy, and reduced
      survival in EOC patients. miR-520g upregulation increased EOC cell proliferation,
      induced cell cycle transition and promoted cell invasion, while miR-520g
      downregulation inhibited tumor-related functions. In vivo, overexpression or
      downregulation of miR-520g respectively generated larger or smaller subcutaneous
      xenografts in nude mice. Death-associated protein kinase 2 (DAPK2) was a direct
      target of miR-520g. In 116 EOC tissue samples, miR-520g expression was
      significantly lower following DAPK2 overexpression. DAPK2 overexpression or miR
      520g knockdown reduced EOC cell proliferation, invasion, wound healing and
      chemoresistance. This study suggests that miR-520g contributes to tumor
      progression and drug resistance by post-transcriptionally downregulating DAPK2,
      and that miR-520g may be a valuable therapeutic target in patients with EOC. 

PMID- 27049922
TI  - Comparing auditory steady-state responses amplitude evoked by simultaneous air-
      and bone-conducted stimulation in newborns.
AB  - OBJECTIVE: The aim of this study was to evaluate the potential interactions of
      the simultaneous presentation of air- and bone-conducted stimuli on auditory
      steady-state responses (ASSR) amplitude in newborns. DESIGN: Bone- and air
      conducted stimuli were sinusoidal carrier tones of 500 and 2000 Hz respectively
      modulated in amplitude (95% depth). Air- and bone- conducted stimuli were either
      simultaneously recorded in the same ear using insert earphones and bone vibrator
      respectively, or recorded individually (single stimulation). STUDY SAMPLE: Sixty
      nine well babies (135 ears) with ages ranging from 1 to 16 days (mean of 9.2 +/-
      7.9 days) were tested in this study. RESULTS: No significant changes in ASSR
      amplitude by air-conducted stimuli were observed when evoked by simultaneous or
      single stimulation. The same trend prevailed for ASSR amplitudes evoked by bone
      conducted stimuli. CONCLUSIONS: The results of this study suggest that the
      simultaneous stimulation of air-and bone-conducted stimuli does not alter ASSR
      amplitude values in well babies. Therefore, the results support the use of this
      technique as a potential hearing screening tool to discriminate between
      conductive and sensorineural hearing loss.

PMID- 27049923
TI  - A multidimensional 'path analysis' model of factors explaining fatigue in
      rheumatoid arthritis.
AB  - OBJECTIVES: Fatigue is one of the most commonly reported symptoms in rheumatoid
      arthritis (RA). Many factors may play a causal role on fatigue in RA patients,
      but their contribution and interplay is barely understood. The objective was to
      develop a multidimensional model of factors that explain fatigue severity in RA.
      METHODS: A cross-sectional study (n=228) of consecutive patients with RA was
      performed. Fatigue, disease characteristics and psychosocial and behavioural
      outcomes were collected. Baseline differences between non severely fatigued
      patients (CIS-fatigue <35) and severely fatigued patients (CIS-fatigue >=35) were
      tested. Structural equation modeling was used to test a hypothesised model for
      fatigue. RESULTS: The final model includes pain, physical functioning, mood,
      sense of control, sleep quality and fatigue, with good fit (CFI=0.976) explaining
      74% of the variance in RA fatigue. Accordingly, poor sleep quality (beta=0.42,
      p<0.001) and less physical functioning (beta=0.65, p<0.001) are directly related
      to a higher level of fatigue. Less sense of control is related to more mood
      disturbance (beta=0.64, p<0.001), more pain (beta=0.389, p<0.001) and less
      physical functioning (beta=-0.24, p<0.001). More mood disturbance is related to
      poor sleep quality (beta=0.78, p<0.001) and higher pain level is related to less
      physical functioning (beta=0.75, p<0.001). CONCLUSIONS: RA fatigue is directly
      influenced by poor sleep quality and physical functioning, and indirectly by
      sense of control, mood and pain. Treatment of these factors by psychological
      interventions and physical exercise could help to improve fatigue in patients
      with RA.

PMID- 27049924
TI  - O,S-Heterocyclic stannylenes: synthesis and reactivity.
AB  - Commercially available N-oxide (2-mercaptopyridine-N-oxide) is used as a ligand
      instead of an oxidizing agent to stabilize the compounds of main group elements
      in low-valent states. The isolated compounds [(C5H4NOS)2Sn (), (C5H4NOS)SnCl ()
      and (C5H4NOS)GeCl ()] are the first structurally characterized examples of O,S
      heterocyclic stannylenes and germylenes with interesting bonding features.
      Further, the reaction of compound with SbCl3 afforded the rare dichlorodiantimony
      oxide [{(C5H4NOS)SbCl}2O] () unprecedentedly.

PMID- 27049925
TI  - Computational Investigation of Technetium(IV) Incorporation into Inverse Spinels:
      Magnetite (Fe3O4) and Trevorite (NiFe2O4).
AB  - Iron oxides and oxyhydroxides play an important role in minimizing the mobility
      of redox-sensitive elements in engineered and natural environments. For the
      radionuclide technetium-99 (Tc), these phases hold promise as primary hosts for
      increasing Tc loading into glass waste form matrices, or as secondary sinks
      during the long-term storage of nuclear materials. Recent experiments show that
      the inverse spinel, magnetite [Fe(II)Fe(III)2O4], can incorporate Tc(IV) into its
      octahedral sublattice. In that same class of materials, trevorite
      [Ni(II)Fe(III)2O4] is also being investigated for its ability to host Tc(IV).
      However, questions remain regarding the most energetically favorable charge
      compensation mechanism for Tc(IV) incorporation in each structure, which will
      affect Tc behavior under changing waste processing or storage conditions. Here,
      quantum-mechanical methods were used to evaluate incorporation energies and
      optimized lattice bonding environments for three different, charge-balanced
      Tc(IV) incorporation mechanisms in magnetite and trevorite (~5 wt % Tc). For both
      phases, the removal of two octahedral Fe(II) or Ni(II) ions upon the addition of
      Tc(IV) in an octahedral site is the most stable mechanism, relative to the
      creation of octahedral Fe(III) defects or increasing octahedral Fe(II) content.
      Following hydration-energy corrections, Tc(IV) incorporation into magnetite is
      energetically favorable while an energy barrier exists for trevorite.

PMID- 27049926
TI  - High School Rowing Injuries: National Athletic Treatment, Injury and Outcomes
      Network (NATION).
AB  - CONTEXT: Data on high school (HS) rowing injuries are lacking. OBJECTIVE: To
      describe the epidemiology of HS boys' and girls' rowing injuries during the 2011
      2012 through 2013-2014 academic years. DESIGN: Descriptive epidemiology study.
      SETTING: Injury and exposure data from 8 and 11 boys' and girls' rowing programs
      providing 13 and 17 team-seasons of data, respectively. PATIENTS OR OTHER
      PARTICIPANTS: High school boys' and girls' varsity rowing student-athletes.
      INTERVENTION(S): High school rowing data from the National Athletic Treatment,
      Injury and Outcomes Network. MAIN OUTCOME MEASURE(S): Injury rates and rate
      ratios were reported with 95% confidence intervals (CIs). RESULTS: In HS boys'
      and girls' rowing, 59 and 190 injuries were reported, respectively, for rates of
      2.39/1000 athlete-exposures (95% CI = 1.78, 3.00) and 8.60/1000 athlete-exposures
      (95% CI = 7.38, 9.82). The girls' rowing injury rate was 3.60 times that of boys'
      (95% CI = 2.69, 4.82). CONCLUSIONS: These findings suggest a higher injury rate
      among HS female rowers than HS male rowers. Additional research exploring reasons
      for the sex difference is warranted.

PMID- 27049927
TI  - Unsaturated Phosphonates as Hauser Acceptors for the Synthesis of Phosphonylated
      Dihydroxynaphthalenes and Naphthoquinones.
AB  - The unsaturated phosphonates were utilized as Hauser acceptors successfully for
      the first time. The products phosphonylated 1,4-dihydroxynaphthalenes were
      isolated in good yields in short reaction time and were further oxidized to the
      corresponding 1,4-naphthoquinones in quantitative yields. The reaction provides
      an efficient and straightforward approach for the synthesis of pharmacologically
      privileged disubstituted naphthalene-1,4-diols and naphtha-1,4-diones bearing a
      phosphonate group at the 2-position and various (het)aryl groups at the 3
      position. 

PMID- 27049928
TI  - Identification and Characterization of CD133(pos) Subpopulation Cells From a
      Human Laryngeal Cancer Cell Line.
AB  - BACKGROUND: Recent research indicates that CD133 are expressed in several kinds
      of stem cells, among which, its high expression in laryngeal carcinoma has caused
      wide concern. To further explore efficaciously targeting drugs to laryngeal
      carcinoma stem cells (CSCs), we transplanted a solid tumor from CSCs into
      abdominal subcutaneous tissue of nude mice, and then compared the biological
      characteristics of laryngeal solid tumors with or without cisplatin intervention.
      MATERIAL/METHODS: In this study, the expression of CD133 was detected in the Hep
      2 cell line by flow cytometry. By applying magnetic cell sorting (MACS)
      technology, we reported the results of purifying CD133-positive cells from a Hep
      2 cell line. Cell proliferation, colony formation, and tumor-forming ability were
      examined in vitro and in vivo to identify the marker of CSCs in Hep-2 cell line.
      RESULTS: Upon flow cytometry analysis, CD133 was expressed constantly on 40.12+/
      1.32% in Hep-2 cell line. Cell proliferation and colony formation ability were
      higher in CD133-positive cells compared to CD133-negative cells, and the in vivo
      tumorigenesis experiment showed the same results as in vitro assay. The 2
      subpopulations cells were both sensitive to DDP, among which, the effect of DPP
      on proliferation ability and tumor-forming ability of CD133-positive cells was
      obviously greater than that of CD133-negative cells. CONCLUSIONS: Above all, our
      study revealed that CD133-positive cells have properties of higher proliferation,
      colony formation, and tumorigenesis in Hep-2 cell line, indicating that CD133
      could be a marker to characterize laryngeal cancer stem cells.

PMID- 27049929
TI  - Synthesis and Application of Novel 3D Magnetic Chlorogenic Acid Imprinted
      Polymers Based on a Graphene-Carbon Nanotube Composite.
AB  - A novel three-dimensional (3D) magnetic chlorogenic acid (CGA) imprinted polymer
      (MMIP) was prepared with novel carbon hybrid nanocomposite as the carrier,
      chlorogenic acid as the template molecule, and methacrylic acid as the functional
      monomer. The 3D MMIPs were characterized by scanning electron microscopy, Fourier
      transform infrared spectroscopy, thermogravimetric analysis, vibrating sample
      magnetometer, and UV spectrometry in detail. The results showed that the
      imprinted layer was attached successfully on the surface of a 3D magnetic carbon
      hybrid nanocomposite. The adsorption performance of the 3D MMIPs was
      investigated, and the results showed that the 3D MMIPs exhibited high adsorption
      capacity and fast adsorption rate toward CGA with a maximum adsorption capacity
      of 10.88 mg g(-1). The extraction conditions involving washing solvent, the pH of
      eluent solvent, elution volume, and desorption time were also investigated in
      detail. Combined with high-performance liquid chromatography, the 3D MMIPs have
      been applied to successfully extract CGA from Eucommia leaf extract samples. 

PMID- 27049930
TI  - Effect of a smoke-free policy on staff attitudes and behaviours within an
      Australian metropolitan health service: a 3 year cross-sectional study.
AB  - Objective In 2010, Peninsula Health (Vic., Australia), became smoke free as part
      of the locally developed smoking prevention and cessation strategy. The aim of
      the present study was to determine the effect of a smoke-free policy on smoking
      status and employee attitudes over a 3-year period. Methods Data were collected
      by three surveys 6 months before and 6 months and 3 years after policy
      introduction. Demographic data, smoking status and attitudes to the introduction
      of the smoke-free policy were collected for analysis. Results There were 3224
      individual responses collected over three time points with similar demographics
      at each time. There were fewer employees smoking at 6 months (P=0.010) and 3
      years (P<0.001) after implementation of the policy. There were more employees who
      felt positive towards the policy 3 years after its introduction (P=0.028). There
      were greater odds of an employee not identifying as a smoker after the policy was
      in place than before the policy was implemented. Conclusions The introduction of
      a smoke-free policy within a health service was an upstream health intervention
      that was well accepted by staff and appeared to have a positive effect on smoking
      behaviours. What is known about the topic? There are an increasing number of
      environmental changes that seek to decrease smoking behaviours. Bans within
      workplaces have a direct effect on employee smoking behaviour. What does this
      paper add? Some employee groups demonstrated the greater odds of smoking when a
      smoke-free policy was in place. Employees felt positive towards this policy. What
      are the implications for practitioners? This policy change supports environmental
      changes affecting individual health-related behaviours.

PMID- 27049931
TI  - Photoluminescent carbon quantum dots as a directly film-forming phosphor towards
      white LEDs.
AB  - Photoluminescent organosilane-functionalized carbon quantum dots (CQDs), 3.0-3.5
      nm in diameter, were synthesized via a facile hydrothermal method using citric
      acid monohydrate as a precursor and N-(3-(trimethoxysilyl) propyl)
      ethylenediamine as a coordinating and passivation agent. The optical properties
      of the as-obtained CQDs were investigated in detail. The CQD aqueous solution
      emits bright blue-white light under ultraviolet (UV) illumination with a quantum
      yield of 57.3% and high red-green-blue (RGB) spectral composition of 60.1%, and
      in particular the CQDs exhibit excitation-independent photoluminescence. The CQDs
      have a narrow size distribution around 3.1 nm and good film-forming ability
      through simple heat-treatment. By virtue of these excellent optical
      characteristics and good film-forming ability, a white light-emitting device
      (LED) was fabricated by combining a UV-LED chip with a single CQD phosphor film,
      which exhibited cool white light with a CIE coordinate of (0.31, 0.36), a color
      rendering index of 84 and a correlated color temperature of 6282 K. In addition,
      the white LED exhibits good optical stability under various working currents and
      for different working time intervals. Moreover, the interaction between the
      carbogenic core and surface groups was discussed using the DMol(3) program based
      on density functional theory. This research suggests the great potential of CQDs
      for solid-state lighting systems and reveals the effect of the surface state on
      the photoluminescent mechanism of CQDs. 

PMID- 27049932
TI  - Preparation of Thin Melanin-Type Films by Surface-Controlled Oxidation.
AB  - The preparation of thin melanin films suitable for applications is challenging.
      In this work, we present a new alternative approach to thin melanin-type films
      using oxidative multilayers prepared by the sequential layer-by-layer deposition
      of cerium(IV) and inorganic polyphosphate. The interfacial reaction between
      cerium(IV) in the multilayer and 5,6-dihydroxyindole (DHI) in the adjacent
      aqueous solution leads to the formation of a thin uniform film. The oxidation of
      DHI by cerium(IV) proceeds via known melanin intermediates. We have characterized
      the formed DHI-melanin films using scanning electron microscopy (SEM), X-ray
      photoelectron spectroscopy (XPS), atomic force microscopy (AFM), UV-vis
      spectroscopy, and spectroelectrochemistry. When a five-bilayer oxidative
      multilayer is used, the film is uniform with a thickness of ca. 10 nm. Its
      chemical composition, as determined using XPS, is typical for melanin. It is also
      redox active, and its oxidation occurs in two steps, which can be assigned to
      semiquinone and quinone formation within the indole structural motif. Oxidative
      multilayers can also oxidize dopamine, but the reaction stops at the dopamine
      quinone stage because of the limited amount of the multilayer-based oxidizing
      agent. However, dopamine oxidation by Ce(IV) was studied also in solution by UV
      vis spectroscopy and mass spectrometry in order to verify the reaction mechanism
      and the final product. In solution, the oxidation of dopamine by cerium shows
      that the indole ring formation takes place already at low pH and that the mass
      spectrum of the final product is practically identical with that of commercial
      melanin. Therefore, layer-by-layer formed oxidative multilayers can be used to
      deposit functional melanin-type thin films on arbitrary substrates by a surface
      controlled reaction.

PMID- 27049933
TI  - The influence of intramolecular sulfur-lone pair interactions on small-molecule
      drug design and receptor binding.
AB  - Sulfur-lone pair interactions are important conformational control elements in
      sulfur-containing heterocycles that abound in pharmaceuticals, natural products,
      agrochemicals, polymers and other important classes of organic molecules.
      Nonetheless, the role of intramolecular sulfur-lone pair interactions in the
      binding of small molecules to receptors is often overlooked. Here we analyze the
      magnitudes and origins of these interactions for a variety of biologically
      relevant small molecules using quantum chemical and automated docking
      calculations. In most cases examined in this study, the lowest energy
      conformation of the small molecule displays a sulfur-lone pair close contact.
      However, docking studies, both published and new, often predict that
      conformations without sulfur-lone pair contacts have the best binding affinity
      for their respective receptors. This is a serious problem. Since many of these
      predicted bound conformations are not actually energetically accessible, pursuing
      design (e.g., drug design) around these binding modes necessarily will lead,
      serendipity aside, to dead end designs. Our results constitute a caution that one
      best not neglect these interactions when predicting the binding affinities of
      potential ligands (drugs or not) for hosts (enzymes, receptors, DNA, RNA,
      synthetic hosts). Moreover, a better understanding and awareness of sulfur-lone
      pair interactions should facilitate the rational modulation of host-guest
      interactions involving sulfur-containing molecules. 

PMID- 27049934
TI  - New Insight of Tetraphenylethylene-based Raman Signatures for Targeted SERS
      Nanoprobe Construction Toward Prostate Cancer Cell Detection.
AB  - We have designed and synthesized novel tetraphenylethylene (TPE) appended organic
      fluorogens and unfold their unique Raman fingerprinting reflected by surface
      enhanced Raman scattering (SERS) upon adsorption on nanoroughened gold surface as
      a new insight in addition to their prevalent aggregation-induced emission (AIE)
      and aggregation-caused quenching (ACQ) phenomena. A series of five TPE analogues
      has been synthesized consisting of different electron donors such as (1) indoline
      with propyl (TPE-In), (2) indoline with lipoic acid (TPE-In-L), (3) indoline with
      Boc-protected propyl amine (TPE-In-Boc), (4) benzothaizole (TPE-B), and (5)
      quinaldine (TPE-Q). Interestingly, all five TPE analogues produced multiplexing
      Raman signal pattern, out of which TPE-In-Boc showed a significant increase in
      signal intensity in the fingerprint region. An efficient SERS nanoprobe has been
      constructed using gold nanoparticles as SERS substrate, and the TPE-In as the
      Raman reporter, which conjugated with a specific peptide substrate, Cys-Ser-Lys
      Leu-Gln-OH, well-known for the recognition of prostate-specific antigen (PSA).
      The designated nanoprobe TPE-In-PSA@Au acted as SERS "ON/OFF" probe in peace with
      the vicinity of PSA protease, which distinctly recognizes PSA expression with a
      limit of detection of 0.5 ng in SERS platform. Furthermore, TPE-In-PSA@Au
      nanoprobe was efficiently recognized the overexpressed PSA in human LNCaP cells,
      which can be visualized through SERS spectral analysis and SERS mapping.

PMID- 27049935
TI  - The effects of perceived organizational support, perceived supervisor support and
      perceived co-worker support on safety and health compliance.
AB  - Although knowledge is cumulating, very little is known about the effects of
      various sources of support on safety and health compliance. This study goes
      beyond previous research by investigating the relationships among perceived
      support from organizations, supervisors and co-workers, and employees' safety and
      health compliance behaviour at chemical and petroleum process plants. The results
      of this study show that the support from organizations, supervisors and co
      workers was significantly related to employees' safety and health compliance.
      Also, the findings reveal that perceived supervisor support has the strongest
      influence in ensuring employees' safety and health compliance behaviour. 

PMID- 27049936
TI  - Dimensionality of Collective Variables for Describing Conformational Changes of a
      Multi-Domain Protein.
AB  - Collective variables (CVs) are often used in molecular dynamics simulations based
      on enhanced sampling algorithms to investigate large conformational changes of a
      protein. The choice of CVs in these simulations is essential because it affects
      simulation results and impacts the free-energy profile, the minimum free-energy
      pathway (MFEP), and the transition-state structure. Here we examine how many CVs
      are required to capture the correct transition-state structure during the open-to
      close motion of adenylate kinase using a coarse-grained model in the mean forces
      string method to search the MFEP. Various numbers of large amplitude principal
      components are tested as CVs in the simulations. The incorporation of local
      coordinates into CVs, which is possible in higher dimensional CV spaces, is
      important for capturing a reliable MFEP. The Bayesian measure proposed by Best
      and Hummer is sensitive to the choice of CVs, showing sharp peaks when the
      transition-state structure is captured. We thus evaluate the required number of
      CVs needed in enhanced sampling simulations for describing protein conformational
      changes. 

PMID- 27049937
TI  - A wild Indo-Pacific bottlenose dolphin adopts a socially and genetically distant
      neonate.
AB  - Alloparental behaviour and adoption have been reported in many mammals and birds.
      Such behaviours are energetically costly, and their causes and functions remain
      unclear. We observed the adoption behaviour of a wild Indo-Pacific bottlenose
      dolphin (Tursiops aduncus) near Mikura Island, Japan. A calf was seen with its
      mother on six observation days. Following the mother's death, the calf was
      observed with a sub-adult female on all 18 observation days from May to September
      2012. On three days, the calf was observed swimming with this female in the
      suckling position and milk was seen leaking from the female's mammary slit. A
      five-year dataset revealed no significant social or kin relationships between the
      biological mother and allomother, indicating that kinship and social
      relationships did not play an important role in the observed adoption. 

PMID- 27049938
TI  - Nuclear physics: Four neutrons together momentarily.

PMID- 27049939
TI  - X-ray structures and mechanism of the human serotonin transporter.
AB  - The serotonin transporter (SERT) terminates serotonergic signalling through the
      sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic
      neurons. SERT is a target for antidepressant and psychostimulant drugs, which
      block reuptake and prolong neurotransmitter signalling. Here we report X-ray
      crystallographic structures of human SERT at 3.15 A resolution bound to the
      antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an
      outward-open conformation by lodging in the central binding site, located between
      transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We
      further identify the location of an allosteric site in the complex as residing at
      the periphery of the extracellular vestibule, interposed between extracellular
      loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the
      allosteric site sterically hinders ligand unbinding from the central site,
      providing an explanation for the action of (S)-citalopram as an allosteric
      ligand. These structures define the mechanism of antidepressant action in SERT,
      and provide blueprints for future drug design. 

PMID- 27049940
TI  - Immunology: Organelle stress triggers inflammation.

PMID- 27049941
TI  - Post-invasion demography of prehistoric humans in South America.
AB  - As the last habitable continent colonized by humans, the site of multiple
      domestication hotspots, and the location of the largest Pleistocene megafaunal
      extinction, South America is central to human prehistory. Yet remarkably little
      is known about human population dynamics during colonization, subsequent
      expansions, and domestication. Here we reconstruct the spatiotemporal patterns of
      human population growth in South America using a newly aggregated database of
      1,147 archaeological sites and 5,464 calibrated radiocarbon dates spanning
      fourteen thousand to two thousand years ago (ka). We demonstrate that, rather
      than a steady exponential expansion, the demographic history of South Americans
      is characterized by two distinct phases. First, humans spread rapidly throughout
      the continent, but remained at low population sizes for 8,000 years, including a
      4,000-year period of 'boom-and-bust' oscillations with no net growth.
      Supplementation of hunting with domesticated crops and animals had a minimal
      impact on population carrying capacity. Only with widespread sedentism, beginning
      ~5 ka, did a second demographic phase begin, with evidence for exponential
      population growth in cultural hotspots, characteristic of the Neolithic
      transition worldwide. The unique extent of humanity's ability to modify its
      environment to markedly increase carrying capacity in South America is therefore
      an unexpectedly recent phenomenon. 

PMID- 27049942
TI  - Structural biology: Antidepressants at work.

PMID- 27049943
TI  - Ubiquitination independent of E1 and E2 enzymes by bacterial effectors.
AB  - Signalling by ubiquitination regulates virtually every cellular process in
      eukaryotes. Covalent attachment of ubiquitin to a substrate is catalysed by the
      E1, E2 and E3 three-enzyme cascade, which links the carboxy terminus of ubiquitin
      to the epsilon-amino group of, in most cases, a lysine of the substrate via an
      isopeptide bond. Given the essential roles of ubiquitination in the regulation of
      the immune system, it is not surprising that the ubiquitination network is a
      common target for diverse infectious agents. For example, many bacterial
      pathogens exploit ubiquitin signalling using virulence factors that function as
      E3 ligases, deubiquitinases or as enzymes that directly attack ubiquitin. The
      bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors
      that modulate diverse host processes to create a permissive niche for its
      replication in phagocytes. Here we demonstrate that members of the SidE effector
      family of L. pneumophila ubiquitinate multiple Rab small GTPases associated with
      the endoplasmic reticulum. Moreover, we show that these proteins are capable of
      catalysing ubiquitination without the need for the E1 and E2 enzymes. A putative
      mono-ADP-ribosyltransferase motif critical for the ubiquitination activity is
      also essential for the role of the SidE family in intracellular bacterial
      replication in a protozoan host. The E1/E2-independent ubiquitination catalysed
      by these enzymes is energized by nicotinamide adenine dinucleotide, which
      activates ubiquitin by the formation of ADP-ribosylated ubiquitin. These results
      establish that ubiquitination can be catalysed by a single enzyme, the activity
      of which does not require ATP. 

PMID- 27049944
TI  - The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune
      suppression.
AB  - Neoplastic pancreatic epithelial cells are believed to die through caspase 8
      dependent apoptotic cell death, and chemotherapy is thought to promote tumour
      apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another
      type of programmed cell death is necroptosis (programmed necrosis), but its role
      in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential
      inducers of necroptosis in PDA, including ligation of tumour necrosis factor
      receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL)
      receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic
      drugs. Here we report that the principal components of the necrosome, receptor
      interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further
      upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in
      vitro promoted cancer cell proliferation and induced an aggressive oncogenic
      phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected
      against oncogenic progression in mice and was associated with the development of
      a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour
      microenvironment associated with intact RIP1/RIP3 signalling depended in part on
      necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1
      blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the
      histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent
      manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating
      myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas
      deletion of Mincle protected against oncogenesis and phenocopied the immunogenic
      reprogramming of the tumour microenvironment that was induced by RIP3 deletion.
      Cellular depletion suggested that whereas inhibitory macrophages promote
      tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or
      Mincle is deleted. Accordingly, T cells, which are not protective against PDA
      progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into
      indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle.
      Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle
      signalling that promote macrophage-induced adaptive immune suppression and
      thereby enable PDA progression.

PMID- 27049945
TI  - Reductive carboxylation supports redox homeostasis during anchorage-independent
      growth.
AB  - Cells receive growth and survival stimuli through their attachment to an
      extracellular matrix (ECM). Overcoming the addiction to ECM-induced signals is
      required for anchorage-independent growth, a property of most malignant cells.
      Detachment from ECM is associated with enhanced production of reactive oxygen
      species (ROS) owing to altered glucose metabolism. Here we identify an
      unconventional pathway that supports redox homeostasis and growth during
      adaptation to anchorage independence. We observed that detachment from monolayer
      culture and growth as anchorage-independent tumour spheroids was accompanied by
      changes in both glucose and glutamine metabolism. Specifically, oxidation of both
      nutrients was suppressed in spheroids, whereas reductive formation of citrate
      from glutamine was enhanced. Reductive glutamine metabolism was highly dependent
      on cytosolic isocitrate dehydrogenase-1 (IDH1), because the activity was
      suppressed in cells homozygous null for IDH1 or treated with an IDH1 inhibitor.
      This activity occurred in absence of hypoxia, a well-known inducer of reductive
      metabolism. Rather, IDH1 mitigated mitochondrial ROS in spheroids, and
      suppressing IDH1 reduced spheroid growth through a mechanism requiring
      mitochondrial ROS. Isotope tracing revealed that in spheroids, isocitrate/citrate
      produced reductively in the cytosol could enter the mitochondria and participate
      in oxidative metabolism, including oxidation by IDH2. This generates NADPH in the
      mitochondria, enabling cells to mitigate mitochondrial ROS and maximize growth.
      Neither IDH1 nor IDH2 was necessary for monolayer growth, but deleting either one
      enhanced mitochondrial ROS and reduced spheroid size, as did deletion of the
      mitochondrial citrate transporter protein. Together, the data indicate that
      adaptation to anchorage independence requires a fundamental change in citrate
      metabolism, initiated by IDH1-dependent reductive carboxylation and culminating
      in suppression of mitochondrial ROS. 

PMID- 27049946
TI  - Modulation of tissue repair by regeneration enhancer elements.
AB  - How tissue regeneration programs are triggered by injury has received limited
      research attention. Here we investigate the existence of enhancer regulatory
      elements that are activated in regenerating tissue. Transcriptomic analyses
      reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of
      zebrafish. Epigenetic profiling identified a short DNA sequence element upstream
      and distal to lepb that acquires open chromatin marks during regeneration and
      enables injury-dependent expression from minimal promoters. This element could
      activate expression in injured neonatal mouse tissues and was divisible into
      tissue-specific modules sufficient for expression in regenerating zebrafish fins
      or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences
      upstream of pro- or anti-regenerative factors controlled the efficacy of
      regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration
      enhancer elements' (TREEs) that trigger gene expression in injury sites and can
      be engineered to modulate the regenerative potential of vertebrate organs. 

PMID- 27049948
TI  - Neuroinflammation: Surprises from the sanitary engineers.

PMID- 27049947
TI  - TAM receptors regulate multiple features of microglial physiology.
AB  - Microglia are damage sensors for the central nervous system (CNS), and the
      phagocytes responsible for routine non-inflammatory clearance of dead brain
      cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate
      these microglial functions. We find that adult mice deficient in microglial Mer
      and Axl exhibit a marked accumulation of apoptotic cells specifically in
      neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic
      cells generated during adult neurogenesis is normally driven by both TAM receptor
      ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that
      the microglial response to brain damage is also TAM-regulated, as TAM-deficient
      microglia display reduced process motility and delayed convergence to sites of
      injury. Finally, we show that microglial expression of Axl is prominently
      upregulated in the inflammatory environment that develops in a mouse model of
      Parkinson's disease. Together, these results establish TAM receptors as both
      controllers of microglial physiology and potential targets for therapeutic
      intervention in CNS disease. 

PMID- 27049949
TI  - A 17-billion-solar-mass black hole in a group galaxy with a diffuse core.
AB  - Quasars are associated with and powered by the accretion of material onto massive
      black holes; the detection of highly luminous quasars with redshifts greater than
      z = 6 suggests that black holes of up to ten billion solar masses already existed
      13 billion years ago. Two possible present-day 'dormant' descendants of this
      population of 'active' black holes have been found in the galaxies NGC 3842 and
      NGC 4889 at the centres of the Leo and Coma galaxy clusters, which together form
      the central region of the Great Wall--the largest local structure of galaxies.
      The most luminous quasars, however, are not confined to such high-density regions
      of the early Universe; yet dormant black holes of this high mass have not yet
      been found outside of modern-day rich clusters. Here we report observations of
      the stellar velocity distribution in the galaxy NGC 1600--a relatively isolated
      elliptical galaxy near the centre of a galaxy group at a distance of 64
      megaparsecs from Earth. We use orbit superposition models to determine that the
      black hole at the centre of NGC 1600 has a mass of 17 billion solar masses. The
      spatial distribution of stars near the centre of NGC 1600 is rather diffuse. We
      find that the region of depleted stellar density in the cores of massive
      elliptical galaxies extends over the same radius as the gravitational sphere of
      influence of the central black holes, and interpret this as the dynamical imprint
      of the black holes.

PMID- 27049950
TI  - A pressure-amplifying framework material with negative gas adsorption
      transitions.
AB  - Adsorption-based phenomena are important in gas separations, such as the
      treatment of greenhouse-gas and toxic-gas pollutants, and in water-adsorption
      based heat pumps for solar cooling systems. The ability to tune the pore size,
      shape and functionality of crystalline porous coordination polymers--or metal
      organic frameworks (MOFs)--has made them attractive materials for such adsorption
      based applications. The flexibility and guest-molecule-dependent response of MOFs
      give rise to unexpected and often desirable adsorption phenomena. Common to all
      isothermal gas adsorption phenomena, however, is increased gas uptake with
      increased pressure. Here we report adsorption transitions in the isotherms of a
      MOF (DUT-49) that exhibits a negative gas adsorption; that is, spontaneous
      desorption of gas (methane and n-butane) occurs during pressure increase in a
      defined temperature and pressure range. A combination of in situ powder X-ray
      diffraction, gas adsorption experiments and simulations shows that this
      adsorption behaviour is controlled by a sudden hysteretic structural deformation
      and pore contraction of the MOF, which releases guest molecules. These findings
      may enable technologies using frameworks capable of negative gas adsorption for
      pressure amplification in micro- and macroscopic system engineering. Negative gas
      adsorption extends the series of counterintuitive phenomena such as negative
      thermal expansion and negative refractive indices and may be interpreted as an
      adsorptive analogue of force-amplifying negative compressibility transitions
      proposed for metamaterials.

PMID- 27049951
TI  - A neuronal circuit for colour vision based on rod-cone opponency.
AB  - In bright light, cone-photoreceptors are active and colour vision derives from a
      comparison of signals in cones with different visual pigments. This comparison
      begins in the retina, where certain retinal ganglion cells have 'colour-opponent'
      visual responses-excited by light of one colour and suppressed by another colour.
      In dim light, rod-photoreceptors are active, but colour vision is impossible
      because they all use the same visual pigment. Instead, the rod signals are
      thought to splice into retinal circuits at various points, in synergy with the
      cone signals. Here we report a new circuit for colour vision that challenges
      these expectations. A genetically identified type of mouse retinal ganglion cell
      called JAMB (J-RGC), was found to have colour-opponent responses, OFF to
      ultraviolet (UV) light and ON to green light. Although the mouse retina contains
      a green-sensitive cone, the ON response instead originates in rods. Rods and
      cones both contribute to the response over several decades of light intensity.
      Remarkably, the rod signal in this circuit is antagonistic to that from cones.
      For rodents, this UV-green channel may play a role in social communication, as
      suggested by spectral measurements from the environment. In the human retina, all
      of the components for this circuit exist as well, and its function can explain
      certain experiences of colour in dim lights, such as a 'blue shift' in twilight.
      The discovery of this genetically defined pathway will enable new targeted
      studies of colour processing in the brain. 

PMID- 27049952
TI  - Corrigendum: Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated
      immune tolerance to cancer.

PMID- 27049953
TI  - Epithelial Label-Retaining Cells Are Absent during Tooth Cycling in Salmo salar
      and Polypterus senegalus.
AB  - The Atlantic salmon (Salmo salar) and African bichir (Polypterus senegalus) are
      both actinopterygian fish species that continuously replace their teeth without
      the involvement of a successional dental lamina. Instead, they share the presence
      of a middle dental epithelium: an epithelial tier enclosed by inner and outer
      dental epithelium. It has been hypothesized that this tier could functionally
      substitute for a successional dental lamina and might be a potential niche to
      house epithelial stem cells involved in tooth cycling. Therefore, in this study
      we performed a BrdU pulse chase experiment on both species to (1) determine the
      localization and extent of proliferating cells in the dental epithelial layers,
      (2) describe cell dynamics and (3) investigate if label-retaining cells are
      present, suggestive for the putative presence of stem cells. Cells proliferate in
      the middle dental epithelium, outer dental epithelium and cervical loop at the
      lingual side of the dental organ to form a new tooth germ. Using long chase
      times, both in S. salar (eight weeks) and P. senegalus (eight weeks and twelve
      weeks), we could not reveal the presence of label-retaining cells in the dental
      organ. Immunostaining of P. senegalus dental organs for the transcription factor
      Sox2, often used as a stem cell marker, labelled cells in the zone of outer
      dental epithelium which grades into the oral epithelium (ODE transition zone) and
      the inner dental epithelium of a successor only. The location of Sox2
      distribution does not provide evidence for epithelial stem cells in the dental
      organ and, more specifically, in the middle dental epithelium. Comparison of S.
      salar and P. senegalus reveals shared traits in tooth cycling and thus advances
      our understanding of the developmental mechanism that ensures lifelong
      replacement. 

PMID- 27049954
TI  - iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate
      Th2 Immune Responses Elicited by Papain in Mice Following gammaPGA Stimulation.
AB  - Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma
      glutamic acid (gammaPGA) treatment suppresses the development of allergic
      diseases such as atopic dermatitis (AD). Although basophils, an innate immune
      cell, are known to play critical roles in allergic immune responses and repeated
      long-term administration of gammaPGA results in decreased splenic basophils in an
      AD murine model, the underlying mechanisms by which gammaPGA regulates basophil
      frequency remain unclear. To investigate how gammaPGA modulates basophils, we
      employed basophil-mediated Th2 induction in vivo model elicited by the allergen
      papain protease. Repeated injection of gammaPGA reduced the abundance of
      basophils and their production of IL4 in mice, consistent with our previous study
      using NC/Nga AD model mice. The depletion of basophils by a single injection of
      gammaPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Valpha14 TCR
      invariant natural killer T (iNKT) cells are known to regulate a variety of immune
      responses, such as allergy. Because iNKT cell activation is highly sensitive to
      IL12 produced by DCs, we evaluated whether the effect of gammaPGA on basophils is
      mediated by iNKT cell activation. We found that in vivo gammaPGA treatment did
      not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice,
      suggesting the critical role of iNKT cells in gammaPGA-mediated basophil
      depletion at the early time points. Furthermore, increased apoptotic basophil
      reduction triggered by iNKT cells upon gammaPGA stimulation was mainly attributed
      to Th1 cytokines such as IFNgamma and TNFalpha, consequently resulting in
      inhibition of papain-induced Th2 differentiation via diminishing basophil-derived
      IL4. Taken together, our results clearly demonstrate that gammaPGA-induced iNKT
      cell polarization toward the Th1 phenotype induces apoptotic basophil depletion,
      leading to the suppression of Th2 immune responses. Thus, elucidation of the
      crosstalk between innate immune cells will contribute to the design and
      development of new therapeutics for Th2-mediated immune diseases such as AD. 

PMID- 27049955
TI  - 4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes
      CD4+CD25+FoxP3+ T Regulatory Cell Suppression.
AB  - Costimulation with the recombinant SA-4-1BBL agonist of 4-1BB receptor on
      conventional CD4+ T cells (Tconvs) overcomes the suppression mediated by
      naturally occurring CD4+CD25+FoxP3+ T regulatory cells (Tregs). The mechanistic
      basis of this observation has remained largely unknown. Herein we show that
      Tconvs, but not Tregs, are the direct target of SA-4-1BBL-mediated evasion of
      Treg suppression. IL-2 produced by Tconvs in response to 4-1BB signaling is both
      necessary and sufficient for overcoming Treg suppression. Supernatant from Tconvs
      stimulated with SA-4-1BBL contains high levels of IL-2 and overcomes Treg
      suppression in ex vivo Tconv:Treg cocultures. Removal of IL-2 from such
      supernatant restores Treg suppression and repletion of Tconv:Treg cocultures with
      exogenous recombinant IL-2 overcomes suppression. This study establishes 4-1BB
      signaling as a key circuit that regulates physical and functional equilibrium
      between Tregs and Tconvs with important implications for immunotherapy for
      indications where a fine balance between Tregs and Teffs plays a decisive role. 

PMID- 27049956
TI  - Cytotoxic activity of physodic acid and acetone extract from Hypogymnia physodes
      against breast cancer cell lines.
AB  - CONTEXT: Lichens produce specific secondary metabolites with different biological
      activity. OBJECTIVE: This study investigated the cytotoxic effects of physodic
      acid, in addition to the total phenolic content and cytotoxic and antioxidant
      activity of acetone extract from Hypogymnia physodes (L.) Nyl. (Parmeliaceae).
      MATERIALS AND METHODS: Cytotoxicity of physodic acid (0.1-100 MUM) was assessed
      in MDA-MB-231, MCF-7 and T-47D breast cancer cell lines and a nontumorigenic MCF
      10A cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,
      neutral red uptake and crystal violet assays during 72 h of incubation. An MTT
      assay was also used to assess the cytotoxic effects of the acetone extract (0.1
      100 MUg/mL) in the MDA-MB-231, MCF-7, T-47D breast cancer cell lines after 72 h.
      The total phenolic content of the acetone extract, expressed as the gallic acid
      equivalent, was investigated using Folin-Ciocalteu reagent. The antioxidant
      activity of the extract was assessed by 2,2-diphenyl-1-picrylhydrazyl and ferric
      reducing antioxidant power assays. RESULTS: The cytotoxic activity of physodic
      acid appeared to be strong in the tumorigenic cell lines (IC50 46.0-93.9 MUM).
      The compound was inactive against the nontumorigenic MCF-10A cell line (IC50 >100
      MUM). The acetone extract showed cytotoxicity in the breast cancer cell lines
      (IC50 46.2-110.4 MUg/mL). The acetone extract was characterized by a high content
      of polyphenols, and it had significant antioxidant activity. DISCUSSION AND
      CONCLUSION: Physodic acid and acetone extract from H. physodes displayed
      cytotoxic effects in the breast cancer cell lines. Furthermore, acetone extract
      from H. physodes possessed significant antioxidant properties.

PMID- 27049957
TI  - Clinical impact of thrombus burden in patients with ST-segment elevation
      myocardial infarction.

PMID- 27049958
TI  - Biomarker ratios and acute myocardial infarction: when one goes up and the other
      goes down.

PMID- 27049959
TI  - Neuropsychological presentation and adaptive skills in high-functioning
      adolescents with visual impairment: A preliminary investigation.
AB  - Studies in infants and young children with congenital visual impairment (VI) have
      indicated early developmental vulnerabilities, conversely research with older
      children and adults have highlighted areas of cognitive strength. A minimal
      amount is known, however, about the possible combination of strengths and
      weaknesses in adolescence, and this present study therefore aims to explore the
      neuropsychological presentation and adaptive behavior profile in high-functioning
      adolescents with congenital VI. Participants completed a battery of commonly used
      neuropsychological measures assessing memory, executive function, and attention.
      The measures utilized focused on auditory neuropsychological function, because
      only subtests that could be completed with auditory administration were suitable
      for this sample. Parents completed standardized measures of adaptive behavior,
      executive function, and social communication. Compared to aged-based norms for
      normal sight, adolescents with VI demonstrated strengths in aspects of working
      memory and verbal memory. Furthermore, performance across the neuropsychological
      battery was within or above the average range for the majority of the sample. In
      contrast, parent-report measures indicated areas of weakness in adaptive
      functioning, social communication, and behavioral executive functioning. Overall,
      this study provides preliminary evidence that relative to fully sighted peers,
      high-functioning adolescents with VI present with an uneven profile of cognitive
      and adaptive skills, which has important implications for assessment and
      intervention.

PMID- 27049960
TI  - A Transitional Gundi (Rodentia: Ctenodactylidae) from the Miocene of Israel.
AB  - We describe a new species of gundi (Rodentia: Ctenodactylidae: Ctenodactylinae),
      Sayimys negevensis, on the basis of cheek teeth from the Early Miocene of the
      Rotem Basin, southern Israel. The Rotem ctenodactylid differs from all known
      ctenodactylid species, including Sayimys intermedius, which was first described
      from the Middle Miocene of Saudi Arabia. Instead, it most resembles Sayimys
      baskini from the Early Miocene of Pakistan in characters of the m1-2 (e.g., the
      mesoflexid shorter than the metaflexid, the obliquely orientated hypolophid, and
      the presence of a strong posterolabial ledge) and the upper molars (e.g., the
      paraflexus that is longer than the metaflexus). However, morphological (e.g.,
      presence of a well-developed paraflexus on unworn upper molars) and dimensional
      (regarding, in particular, the DP4 and M1 or M2) differences between the Rotem
      gundi and Sayimys baskini distinguish them and testify to the novelty and
      endemicity of the former. In its dental morphology, Sayimys negevensis sp. nov.
      shows a combination of both the ultimate apparition of key-characters and
      incipient features that would be maintained and strengthened in latter
      ctenodactylines. Thus, it is a pivotal species that bridges the gap between an
      array of primitive ctenodactylines and the most derived, Early Miocene and later,
      gundis. 

PMID- 27049961
TI  - Development and validation of a correction equation for Corvis tonometry.
AB  - PRIMARY OBJECTIVE: This study uses numerical analysis and validation against
      clinical data to develop a method to correct intraocular pressure (IOP)
      measurements obtained using the Corvis Tonometer for the effects of central
      corneal thickness (CCT), and age. MATERIALS AND METHODS: Finite element analysis
      was conducted to simulate the effect of tonometric air pressure on the intact eye
      globe. The analyses considered eyes with wide variations in IOP (10-30 mm Hg),
      CCT (445-645 microns), R (7.2-8.4 mm), shape factor, P (0.6-1) and age (30-90
      years). In each case, corneal deformation was predicted and used to estimate the
      IOP measurement by Corvis (CVS-IOP). Analysis of the results led to an algorithm
      relating estimates of true IOP as a function of CVS-IOP, CCT and age. All other
      parameters had negligible effect on CVS-IOP and have therefore been omitted from
      the algorithm. Predictions of corrected CVS-IOP, as obtained by applying the
      algorithm to a clinical data-set involving 634 eyes, were assessed for their
      association with the cornea stiffness parameters; CCT and age. RESULTS: Analysis
      of CVS-IOP measurements within the 634-large clinical data-set showed strong
      correlation with CCT (3.06 mm Hg/100 microns, r(2) = 0.204) and weaker
      correlation with age (0.24 mm Hg/decade, r(2) = 0.009). Applying the algorithm to
      IOP measurements resulted in IOP estimations that became less correlated with
      both CCT (0.04 mm Hg/100 microns, r(2) = 0.005) and age (0.09 mm Hg/decade, r(2)
      = 0.002). CONCLUSIONS: The IOP correction process developed in this study was
      successful in reducing reliance of IOP measurements on both corneal thickness and
      age in a healthy European population.

PMID- 27049962
TI  - Inter-Fraction Tumor Volume Response during Lung Stereotactic Body Radiation
      Therapy Correlated to Patient Variables.
AB  - PURPOSE: Analyze inter-fraction volumetric changes of lung tumors treated with
      stereotactic body radiation therapy (SBRT) and determine if the volume changes
      during treatment can be predicted and thus considered in treatment planning.
      METHODS AND MATERIALS: Kilo-voltage cone-beam CT (kV-CBCT) images obtained
      immediately prior to each fraction were used to monitor inter-fraction volumetric
      changes of 15 consecutive patients (18 lung nodules) treated with lung SBRT at
      our institution (45-54 Gy in 3-5 fractions) in the year of 2011-2012. Spearman's
      (rho) correlation and Spearman's partial correlation analysis was performed with
      respect to patient/tumor and treatment characteristics. Multiple hypothesis
      correction was performed using False Discovery Rate (FDR) and q-values were
      reported. RESULTS: All tumors studied experienced volume change during treatment.
      Tumor increased in volume by an average of 15% and regressed by an average of
      11%. The overall volume increase during treatment is contained within the
      planning target volume (PTV) for all tumors. Larger tumors increased in volume
      more than smaller tumors during treatment (q = 0.0029). The volume increase on
      CBCT was correlated to the treatment planning gross target volume (GTV) as well
      as internal target volumes (ITV) (q = 0.0085 and q = 0.0039 respectively) and
      could be predicted for tumors with a GTV less than 22 mL. The volume increase was
      correlated to the integral dose (ID) in the ITV at every fraction (q = 0.0049).
      The peak inter-fraction volume occurred at an earlier fraction in younger
      patients (q = 0.0122). CONCLUSIONS: We introduced a new analysis method to follow
      inter-fraction tumor volume changes and determined that the observed changes
      during lung SBRT treatment are correlated to the initial tumor volume, integral
      dose (ID), and patient age. Furthermore, the volume increase during treatment of
      tumors less than 22mL can be predicted during treatment planning. The volume
      increase remained significantly less than the overall PTV expansion, and
      radiation re-planning was therefore not required for the purpose of tumor
      control. The presence of the studied correlations suggests that the observed
      volumetric changes may reflect some underlying biologic process rather than
      random fluctuations.

PMID- 27049963
TI  - Payments for Environmental Services in a Policymix: Spatial and Temporal
      Articulation in Mexico.
AB  - Government based Payments for Ecosystem Services (PES) have been criticized for
      not maximizing environmental effectiveness through appropriate targeting, while
      instead prioritizing social side-objectives. In Mexico, existing literature on
      how the Payments for Ecosystem Services-Hydrological program (PSA-H) has targeted
      deforestation and forest degradation shows that both the process of identifying
      the eligible areas and the choice of the selection criteria for enrolling forest
      parcels have been under the influence of competing agendas. In the present paper
      we study the influence of the PSA-H multi-level governance on the environmental
      effectiveness of the program-the degree to which forest at high risk of
      deforestation is enrolled- building from a "policyscape" framework. In
      particular, we combine governance analysis with two distinct applications of the
      policyscape framework: First, at national level we assess the functional overlap
      between the PSA-H and other environmental and rural programs with regard to the
      risk of deforestation. Second, at regional level in the states of Chiapas and
      Yucatan, we describe the changing policy agenda and the role of technical
      intermediaries in defining the temporal spatialization of the PSA-H eligible and
      enrolled areas with regard to key socio-economic criteria. We find that, although
      at national level the PSA-H program has been described as coping with both social
      and environmental indicators thanks to successful adaptive management, our
      analysis show that PSA-H is mainly found in communities where deforestation risk
      is low and in combination with other environmental programs (protected areas and
      forest management programs). Such inertia is reinforced at regional level as a
      result of the eligible areas' characteristics and the behaviour of technical
      intermediaries, which seek to minimise transaction costs and sources of
      uncertainty. Our project-specific analysis shows the importance of integrating
      the governance of a program in the policyscape framework as a way to better
      systematize complex interactions at different spatial and institutional scales
      between policies and landscape characteristics. 

PMID- 27049964
TI  - Performance Assessment of Full-Scale Wastewater Treatment Plants Based on
      Seasonal Variability of Microbial Communities via High-Throughput Sequencing.
AB  - Microbial communities of activated sludge (AS) play a key role in the performance
      of wastewater treatment processes. However, seasonal variability of microbial
      population in varying AS-based processes has been poorly correlated with
      operation of full-scale wastewater treatment systems (WWTSs). In this paper,
      significant seasonal variability of AS microbial communities in eight WWTSs
      located in the city of Guangzhou were revealed in terms of 16S rRNA-based Miseq
      sequencing. Furthermore, variation redundancy analysis (RDA) demonstrated that
      the microbial community compositions closely correlated with WWTS operation
      parameters such as temperature, BOD, NH4+-N and TN. Consequently, support vector
      regression models which reasonably predicted effluent BOD, SS and TN in WWTSs
      were established based on microbial community compositions. This work provided an
      alternative tool for rapid assessment on performance of full-scale wastewater
      treatment plants. 

PMID- 27049965
TI  - Joint Estimation of Contamination, Error and Demography for Nuclear DNA from
      Ancient Humans.
AB  - When sequencing an ancient DNA sample from a hominin fossil, DNA from present-day
      humans involved in excavation and extraction will be sequenced along with the
      endogenous material. This type of contamination is problematic for downstream
      analyses as it will introduce a bias towards the population of the contaminating
      individual(s). Quantifying the extent of contamination is a crucial step as it
      allows researchers to account for possible biases that may arise in downstream
      genetic analyses. Here, we present an MCMC algorithm to co-estimate the
      contamination rate, sequencing error rate and demographic parameters-including
      drift times and admixture rates-for an ancient nuclear genome obtained from human
      remains, when the putative contaminating DNA comes from present-day humans. We
      assume we have a large panel representing the putative contaminant population
      (e.g. European, East Asian or African). The method is implemented in a C++
      program called 'Demographic Inference with Contamination and Error' (DICE). We
      applied it to simulations and genome data from ancient Neanderthals and modern
      humans. With reasonable levels of genome sequence coverage (>3X), we find we can
      recover accurate estimates of all these parameters, even when the contamination
      rate is as high as 50%. 

PMID- 27049966
TI  - United Kingdom: Health System Review.
AB  - This analysis of the United Kingdom health system reviews recent developments in
      organization and governance, health financing, health care provision, health
      reforms and health system performance. It provides an overview of how the
      national health services operate in the four nations that make up the United
      Kingdom, as responsibility for organizing health financing and services was
      devolved from 1997. With devolution, the health systems in the United Kingdom
      have diverged in the details of how services are organized and paid for, but all
      have maintained national health services which provide universal access to a
      comprehensive package of services that are mostly free at the point of use. These
      health services are predominantly financed from general taxation and 83.5% of
      total health expenditure in the United Kingdom came from public sources in 2013.
      Life expectancy has increased steadily across the United Kingdom, but health
      inequalities have proved stubbornly resistant to improvement, and the gap between
      the most deprived and the most privileged continues to widen, rather than close.
      The United Kingdom faces challenges going forward, including how to cope with the
      needs of an ageing population, how to manage populations with poor health
      behaviours and associated chronic conditions, how to meet patient expectations of
      access to the latest available medicines and technologies, and how to adapt a
      system that has limited resources to expand its workforce and infrastructural
      capacity so it can rise to these challenges. 

PMID- 27049967
TI  - Moving beyond the platinum sensitive/resistant paradigm for patients with
      recurrent ovarian cancer.

PMID- 27049968
TI  - Familial incidence of the congenital torcular dural arteriovenous shunt: Case
      report and review of the literature.
AB  - Congenital dural sinus malformations are rare but can be major causes of
      mortality and morbidity in the pediatric population if not detected and managed
      urgently. Lesions involving large draining sinus structures such as superior
      sagittal sinus and torcular herophili can result in significant intracranial
      circulation impairment mostly due to venous drainage disturbance. Early detection
      plays a pivotal role in the outcome of the patients. Rarely familial incidence of
      some types of arteriovenous malformations in isolation from other congenital
      hereditary disorders has been reported. Knowledge of the familial association of
      congenital dural sinus malformations may raise the awareness for considering the
      possibility of occurrence of these lesions in the relatives of index cases.
      Herein, we describe the occurrence of giant torcular dural shunt in two pediatric
      cousins treated with endovascular embolization. 

PMID- 27049969
TI  - Emergence of KPC-producing Klebsiella pneumoniae hypervirulent clone of capsular
      serotype K1 that belongs to sequence type 11 in Mainland China.
AB  - KPC-2 has been rarely reported in hypervirulent Klebsiella pneumoniae strains.
      Here, we describe a KPC-2-producing K. pneumoniae hypervirulent clone of capsular
      serotype K1 belonging to sequence type 11. The presence of KPC carbapenemase in
      hypervirulent clone could mark an evolutionary step toward its establishment as
      major nosocomial pathogen. 

PMID- 27049970
TI  - A liposomal formulation for the oral application of the investigational hepatitis
      B drug Myrcludex B.
AB  - The aim of this study was the development of a liposomal formulation containing
      specific tetraether lipids for the oral administration of the investigational
      hepatitis B peptide drug Myrcludex B. For this purpose, tetraether lipids were
      extracted from the extremophilic archaeon Sulfolobus acidocaldarius and purified
      in order to obtain the desired glycerylcaldityltetraether lipids (GCTE).
      Myrcludex B was synthesized by solid-phase synthesis and incorporated into
      liposomes containing 5mol% of GCTE. These liposomes showed a size, polydispersity
      index and zeta potential comparable to the standard liposomes. Cryo-EM
      micrographs of both liposomal formulations displayed low lamellarity, the
      prerequisite for high drug loading capacity. Long term storage of the GCTE
      liposomes was achieved by freeze-drying using 100-500mM sucrose or trehalose as
      lyoprotectors. The lyophilized product showed high stability with a recovery rate
      of 82.7+/-1.6% of intact Myrcludex B observed after storage for 3months at -20
      degrees C as compared to a recovery rate of 83.3+/-1.3% directly after the freeze
      drying process. In vivo, the GCTE-liposomal formulation led to substantial
      enhancement of the liver uptake of iodine-131-labeled Myrcludex B in Wistar rats.
      3h after oral application, approximately 7% of the initial dose (corresponding to
      a 3.5-fold increase compared to the free peptide) could be detected in the liver.
      In summary, the GCTE-liposomes enabled efficient oral administration of Myrcludex
      B and provided long term storage by freeze-drying. 

PMID- 27049971
TI  - A cross-sectional analysis of the association between marijuana and cigarette
      smoking with metabolic syndrome among adults in the United States.
AB  - AIM: To assess the relationship between marijuana use, cigarette smoking and
      metabolic syndrome among adults in the United States who reported they use
      marijuana or cigarettes in comparison to non-marijuana and non-cigarette users.
      METHOD: We conducted multiple logistic regression analyses using data from the
      2011-2012 United States National Health and Nutrition Examination Survey to
      estimate relationships between cardio-metabolic risk factors and increasing years
      of smoking cigarette or marijuana use. Statistical adjustments were made for both
      demographic and endogenous factors related to recreational substance use.
      RESULTS: Each year increase in marijuana use was significantly associated with
      increased odds of metabolic syndrome (OR=1.05; 95% CI: 1.01, 1.09), and
      hypertension (OR=1.04; 95% CI: 1.01, 1.07) adjusting for both demographic and
      endogenous factors related to recreational substance use. Each year increase in
      cigarette smoking was significantly associated with increased odds of
      hypertension (OR=1.03; 95% CI: 1.00, 1.06) and hyperglycemia (OR=1.03; 95% CI:
      1.01, 1.05) after adjusting for confounders. CONCLUSION: The results of this
      investigation suggest that increased years of marijuana or cigarette use are
      important factors in metabolic health; and consequently calls for the need to
      consider the potential negative effects of marijuana or cigarette for metabolic
      syndrome and its associated cardio-metabolic risk components.

PMID- 27049972
TI  - Research should be a part of every nurse's life.

PMID- 27049974
TI  - Training 'not reaching everyone'.

PMID- 27049973
TI  - Patients still left in the dark about palliative care, national audit finds.

PMID- 27049976
TI  - NHS unveils national policy for whistleblowers.

PMID- 27049975
TI  - Two UK schools of nursing are world-beaters.

PMID- 27049977
TI  - Call for nurses to speak up about how climate change is affecting their work.

PMID- 27049979
TI  - 'Meagre' uplift in nurse numbers is no match for surge in demand.

PMID- 27049978
TI  - It's 2016 and profession still seen as a girls' job.

PMID- 27049980
TI  - Multimorbidity draft rules published for consultation.

PMID- 27049981
TI  - Cash boost to rare dementia research.

PMID- 27049983
TI  - Information is given a mat finish.

PMID- 27049984
TI  - Noise levels in intensive care units similar to those of busy restaurants.

PMID- 27049990
TI  - Epilepsy.

PMID- 27049991
TI  - Why nursing research matters.
AB  - To coincide with the RCN international nursing research conference in Edinburgh
      we take a look at the state of nursing research. It has come a long way in a
      short time, but a key challenge is ensuring the aim is firmly on studies that
      benefit frontline practice.

PMID- 27049992
TI  - Mental health and loneliness in old age.
AB  - Researcher Vasiliki Tzouvara will be presenting the results of her study into
      loneliness among nursing home residents at the RCN international nursing research
      conference in Edinburgh. She believes more initiatives should be targeted at this
      population.

PMID- 27049993
TI  - Patient's Choice: vote for your favourite.

PMID- 27050005
TI  - Meningitis Signs and Symptoms.

PMID- 27050006
TI  - A L 600 million stick to beat us with so we're forced to eat more carrots.

PMID- 27050007
TI  - Raise pay to halt this artificial nursing recruitment crisis.

PMID- 27050008
TI  - Autocratic leaders belong in the forces not in nursing.

PMID- 27050009
TI  - Get your rightful tax relief without losing a penny of it.

PMID- 27050010
TI  - Most experienced nurses need to return to the bedside.

PMID- 27050013
TI  - How to perform transrectal ultrasound and prostate biopsy.

PMID- 27050014
TI  - Facilitation of learning: part 1.
AB  - This article, the fourth in a series of 11, discusses the context for the
      facilitation of learning. It outlines the main principles and theories for
      understanding the process of learning, including examples which link these
      concepts to practice. The practical aspects of using these theories in a practice
      setting will be discussed in the fifth article of this series. Together, these
      two articles will provide mentors and practice teachers with knowledge of the
      learning process, which will enable them to meet the second domain of the Nursing
      and Midwifery Council's Standards to Support Learning and Assessment in Practice
      on facilitation of learning. 

PMID- 27050015
TI  - Role of the nurse in managing complaints in their clinical area.
AB  - Complaints and their management are an important indicator of the quality of
      care. Therefore, effective management of complaints is central to improve
      services and prioritise an open, honest and transparent health service. However,
      there is scope for NHS organisations to improve their response to complaints.
      This article outlines the NHS complaints procedure, focusing on how nurses can
      develop essential skills to help them to improve their management of any
      complaints that arise in their clinical area. It provides a structured framework,
      identifying useful communication skills, and explores how managing complaints
      relates to a nurse's statutory duty of candour. 

PMID- 27050016
TI  - Osteoarthritis.

PMID- 27050017
TI  - A different perspective.

PMID- 27050018
TI  - Why work in nursing research?

PMID- 27050020
TI  - 'I caught the research bug'.

PMID- 27050021
TI  - Economic burden of hepatitis B infection among patients with diabetes.
AB  - Despite ACIP recommendation and cost-effectiveness established in those 19-59 y
      old diabetes patients the uptake of Hepatitis B vaccine in diabetes patients is
      low. There is need to highlight the impact of Hepatitis B virus (HBV) infection
      in diabetes patients in terms of healthcare utilization and costs to recognize
      the burden of HBV in this population. This retrospective claims analysis included
      patients with diabetes and HBV (cases; n=1,236) and those with diabetes without
      HBV (controls; n=4,944), identified by ICD-9-CM diagnosis codes. Cases were
      matched with 4 controls using propensity score matching. Healthcare utilization
      and cost were compared; incremental effect of HBV infection was assessed using
      multivariate analysis. In the adjusted analyses, the mean number of
      hospitalizations (0.6 vs 0.4), outpatient service visits (34.2 vs. 20.4), and
      office visits (10.9 vs. 9.8) were 41%, 68%, and 11% higher, respectively, in
      cases vs. controls (all p<0.05). Gastroenterologist visits (0.8 vs. 0.2) and
      infectious disease visits (0.1 vs. 0.0) were 80% and 18% higher in subset of case
      and controls with these events. Cases ($39,435) incurred $16,397 incremental
      total costs compared with controls ($23,038). Medical ($30,968 vs. $17,765) and
      pharmacy costs ($8,029 vs. $5,114) were both significantly higher for cases (p <
      0.0001). Healthcare utilization and costs were higher among patients with
      diabetes and HBV than in those with diabetes alone. These results provide
      evidence supporting the need for HBV vaccination among unvaccinated diabetes
      patients.

PMID- 27050022
TI  - Arthroscopic Talar Dome Access Using a Standard Versus Wire-Based Traction Method
      for Ankle Joint Distraction.
AB  - PURPOSE: To evaluate the accessibility of the talar dome through anterior and
      posterior portals for ankle arthroscopy with the standard noninvasive distraction
      versus wire-based longitudinal distraction using a tensioned wire placed
      transversely through the calcaneal tuberosity. METHODS: Seven matched pairs of
      thigh-to-foot specimens underwent ankle arthroscopy with 1 of 2 methods of
      distraction: a standard noninvasive strapping technique or a calcaneal tuberosity
      wire-based technique. The order of the arthroscopic approach and use of a
      distraction method was randomly determined. The areas accessed from both 2-portal
      anterior and 2-portal posterior approaches were determined by using a molded
      translucent grid. RESULTS: The mean talar surface accessible by anterior ankle
      arthroscopy was comparable with noninvasive versus calcaneal wire distraction
      with 57.8% +/- 17.2% (range, 32.9% to 75.7%) versus 61.5% +/- 15.2% (range, 38.5%
      to 79.1%) of the talar dome, respectively (P = .590). The use of calcaneal wire
      distraction significantly improved posterior talar dome accessibility compared
      with noninvasive distraction, with 56.4% +/- 20.0% (range, 14.4% to 78.0%) versus
      39.8% +/- 14.9% (range, 20.0% to 57.6%) of the talar dome, respectively (P =
      .031). CONCLUSIONS: Under the conditions studied, our cadaveric model showed
      equivalent talar dome access with 2-portal anterior arthroscopy of calcaneal wire
      based distraction versus noninvasive strap distraction, but improved access for 2
      portal posterior arthroscopy with calcaneal wire-based distraction versus
      noninvasive strap distraction. CLINICAL RELEVANCE: The posterior 40% of the talar
      dome is difficult to access via anterior ankle arthroscopy. Posterior calcaneal
      tuberosity wire-based longitudinal distraction improved arthroscopic access to
      the centro-posterior talar dome with a posterior arthroscopic approach.

PMID- 27050023
TI  - Measurement of Coracohumeral Distance in 3 Shoulder Positions Using Dynamic
      Ultrasonography: Correlation With Subscapularis Tear.
AB  - PURPOSE: To detect differences between the values of dynamic coracohumeral
      distance (CHD) measured using ultrasonography (USG) in different shoulder
      rotations and to investigate its correlation with subscapularis tear. METHODS: We
      prospectively enrolled consecutive patients (n = 168) who were scheduled to have
      arthroscopic rotator cuff repair. Patients with a history of previous shoulder
      surgery or shoulder fracture and patients with external rotation less than 30
      degrees  were excluded from the study. Dynamic CHD was measured using USG in 3
      different shoulder positions: external rotation, neutral and internal rotation.
      We evaluated the intrarater reliability with 3 times repetition of measurement.
      Patients were divided into 1 of 3 groups according to arthroscopic findings:
      intact subscapularis, partial-thickness tear, and full-thickness tear of the
      subscapularis. The control group (n = 23) included patients without rotator cuff
      tears from the outpatient clinic. Subgroup analysis-according to the presence of
      dynamic subcoracoid stenosis, defined as a CHD less than 6 mm measured in
      internal rotation-was performed to find the clinical effect of dynamic
      subcoracoid stenosis. RESULTS: A partial-thickness tear of the subscapularis
      tendon was present in 60 patients (35.7%) and a full-thickness tear in 26
      patients (15.4%) among 168 patients. The CHD was maximum in external rotation and
      the narrowest in internal rotation. There were no statistical differences in the
      CHDs between groups with different subscapularis tear status. According to the
      presence of dynamic subcoracoid stenosis, patients with dynamic subcoracoid
      stenosis had a significantly higher incidence of partial-thickness subscapularis
      tear than those without stenosis (P = .022). CONCLUSIONS: The CHD values were
      narrowest in shoulder internal rotation, which is thought to be the pathogenic
      position. We could not confirm the correlation between CHD and subscapularis
      tear. However, patients who have dynamic subcoracoid stenosis had significantly
      higher incidence of subscapularis tear than others without dynamic stenosis.
      LEVEL OF EVIDENCE: Level II, prospective prognostic cohort study.

PMID- 27050024
TI  - Food environments in schools and in the immediate vicinity are associated with
      unhealthy food consumption among Brazilian adolescents.
AB  - BACKGROUND: Evidence of the influence of the school food environment on
      adolescent diet is still little explored in low- and middle-income countries. We
      aimed to evaluate the association between food environment in schools and the
      immediate vicinity and the regular consumption of unhealthy food among
      adolescents. METHODS: We used cross-sectional data collected by the Brazilian
      National Survey of School Health (PeNSE) from a representative sample of
      adolescents attending 9th grade public and private schools in Brazil, in 2012. We
      estimated students' regular consumption (>5days/week) of unhealthy food (soft
      drinks, bagged salty snacks, deep fried salty snacks and sweets) and school
      availability, in the cafeteria or an alternative outlet, of the same food plus
      some healthy options (fruit and natural fruit juice). We performed multilevel
      logistic regression models. RESULTS: Having a cafeteria inside school selling
      soft drinks (private schools OR=1.23; 95% CI=1.14-1.33; public schools OR=1.13;
      95% CI=1.06-1.20) and deep fried salty snacks (private schools OR=1.41 95%
      CI=1.26-1.57; public schools OR=1.16 95% CI=1.08-1.24) was associated with a
      higher consumption of these unhealthy foods of among students. In private
      schools, cafeteria selling fruit and natural fruit juice was associated with
      lower student consumption of bagged salty snacks (OR=0.86; 95% CI 0.77-0.96) and
      soft drinks (OR=0.85; 95% CI=0.76-0.94). In addition, eating meals from the
      Brazilian School Food Program in public schools was associated with a lower
      consumption of unhealthy foods. CONCLUSIONS: Foods available in the school food
      environment are associated with the consumption of unhealthy food among
      adolescents in Brazil.

PMID- 27050025
TI  - Rationale and design of the PERFECTION (comparison between stress cardiac
      computed tomography PERfusion versus Fractional flow rEserve measured by Computed
      Tomography angiography In the evaluation of suspected cOroNary artery disease)
      prospective study.
AB  - BACKGROUND: Non-invasive stress tests are commonly used as gatekeepers to
      invasive coronary angiography (ICA) in patients with suspected coronary artery
      disease (CAD). New computed tomography angiography (CTA) techniques such as
      fractional flow reserve calculated by CTA (FFRCT) and stress myocardial computed
      tomography perfusion (CTP) have emerged as potential strategies to combine
      anatomical and functional evaluation of CAD in one technique. The aim of this
      study is to compare per-vessel diagnostic accuracy of FFRCT versus stress
      myocardial CTP for the detection of functionally significant coronary artery
      disease (CAD), using invasive FFR as the reference standard. METHODS: Subjects
      with suspected CAD due to chest pain who have no contra-indications to FFRCT or
      stress myocardial CTP and who are referred for non-emergent, clinically indicated
      invasive coronary angiography (ICA), will be enrolled. A total of 300 subjects
      will be enrolled within 24 months. RESULTS: The primary study endpoint will be
      the comparison of per-vessel diagnostic accuracy of CTA versus FFRCT versus
      stress myocardial CTP for the diagnosis of hemodynamically significant stenosis
      as defined by invasive FFR <=0.80. CONCLUSIONS: In the PERFECTION study, the
      comparison between FFRCT and stress myocardial CTP will provide understanding
      about which technology is more accurate for the diagnosis of functionally
      significant CAD.

PMID- 27050026
TI  - Evidence regarding the utility of multiple mini-interview (MMI) for selection to
      undergraduate health programs: A BEME systematic review: BEME Guide No. 37.
AB  - BACKGROUND: In the 11 years since its development at McMaster University Medical
      School, the multiple mini-interview (MMI) has become a popular selection tool. We
      aimed to systematically explore, analyze and synthesize the evidence regarding
      MMIs for selection to undergraduate health programs. METHODS: The review protocol
      was peer-reviewed and prospectively registered with the Best Evidence Medical
      Education (BEME) collaboration. Thirteen databases were searched through 34 terms
      and their Boolean combinations. Seven key journals were hand-searched since 2004.
      The reference sections of all included studies were screened. Studies meeting the
      inclusion criteria were coded independently by two reviewers using a modified
      BEME coding sheet. Extracted data were synthesized through narrative synthesis.
      RESULTS: A total of 4338 citations were identified and screened, resulting in 41
      papers that met inclusion criteria. Thirty-two studies report data for selection
      to medicine, six for dentistry, three for veterinary medicine, one for pharmacy,
      one for nursing, one for rehabilitation, and one for health science. Five studies
      investigated selection to more than one profession. MMIs used for selection to
      undergraduate health programs appear to have reasonable feasibility,
      acceptability, validity, and reliability. Reliability is optimized by including 7
      12 stations, each with one examiner. The evidence is stronger for face validity,
      with more research needed to explore content validity and predictive validity. In
      published studies, MMIs do not appear biased against applicants on the basis of
      age, gender, or socio-economic status. However, applicants of certain ethnic and
      social backgrounds did less well in a very small number of published studies.
      Performance on MMIs does not correlate strongly with other measures of
      noncognitive attributes, such as personality inventories and measures of
      emotional intelligence. DISCUSSION: MMI does not automatically mean a more
      reliable selection process but it can do, if carefully designed. Effective MMIs
      require careful identification of the noncognitive attributes sought by the
      program and institution. Attention needs to be given to the number of stations,
      the blueprint and examiner training. CONCLUSION: More work is required on MMIs as
      they may disadvantage groups of certain ethnic or social backgrounds. There is a
      compelling argument for multi-institutional studies to investigate areas such as
      the relationship of MMI content to curriculum domains, graduate outcomes, and
      social missions; relationships of applicants' performance on different MMIs; bias
      in selecting applicants of minority groups; and the long-term outcomes
      appropriate for studies of predictive validity.

PMID- 27050027
TI  - Clinical diagnosis and treatment of a patient with low back pain using the
      patient response model: A case report.
AB  - The medical management of low back pain (LBP) can be approached in a multitude of
      ways. Classification via subgrouping is increasingly common in orthopedic
      literature. Clinical diagnosis and treatment of LBP using the patient response
      model (PRM) can assist clinicians in hypothesizing the origin of pain and
      providing beneficial interventions unlike the widely used pathoanatomical model.
      This case report involved a 52-year-old female with sudden onset of right-sided
      LBP that radiated to the foot. These symptoms were accompanied by occasional
      paresthesias in bilateral lower extremities. Magnetic resonance imaging (MRI)
      confirmed disc bulges at levels T11-T12 and T12-L1. On the first of seven visits,
      she reported 9/10 on the Numeric Pain Rating Scale (NPRS), scored a 24/50 on the
      modified Oswestry disability index (mODI), and demonstrated lumbar flexion range
      of motion (ROM) of 10 degrees . Using the PRM, the patient was classified as an
      extension responder and was instructed to perform 10 repetitions of standing
      lumbar extension every 2 waking hours. After 4 weeks of therapy, the patient
      reported a 1/10 pain localized to the low back, scored 20/50 on the mODI, and
      improved flexion ROM to 45 degrees . Classification using the PRM yielded
      positive outcomes with this patient's symptoms and daily function. 

PMID- 27050028
TI  - A Randomized Controlled Trial of Omega 3 Fatty Acids in Rosacea Patients with Dry
      Eye Symptoms.
AB  - : Objective or purpose: To evaluate the efficacy of dietary omega-3 fatty acids
      (O3FAs) in rosacea patients having dry eye symptoms. METHODS: A prospective,
      interventional, randomized, double-masked, placebo-controlled, multi-centric
      study was done. Symptomatic patients with rosacea were recruited based on their
      response to (Dry Eye Scoring System, DESS(c)); a score of 0-3 was assigned to dry
      eye-related symptoms like ocular fatigue, blurring of vision, itching or burning,
      sandy or gritty sensation, and redness, respectively (DESS(c)). Subjects were (n
      = 130) were randomized to receive either O3FAs (n = 65) or placebo (n = 65)
      capsules (olive oil) twice daily for 6 months. Patients were evaluated at
      baseline, 1, 3, and 6 months. Change in subjective dry eye symptoms was the
      primary outcome measure. Change in meibomian gland score (MGS), Schirmer score,
      and tear film breakup time (TBUT) were the secondary outcome measures. RESULTS:
      Repeated-measures ANOVA revealed that there was a significant (p < 0.001) change
      in symptoms (F(1.506, 88.825 = 315.193), MGS (F(1.336, 78.796 = 84.438), Schirmer
      score (F(1.322, 78.022 = 86.559), and TBUT (F(1.354, 79.898 = 179.020.559) in
      O3FA group as compared to placebo group. Post-hoc test revealed that there was a
      significant change in dry eye symptoms at all points of time; there was a
      significant change in MGS, Schirmer score, and TBUT also, but only after 3 months
      of intervention. Linear regression established that symptom severity could
      significantly predict MGS, Schirmer score, and TBUT. There was a significant
      change in the slope (intercept) of the regression plots in O3FA group as compared
      to the placebo group. CONCLUSION: Rosacea patients with dry eye symptoms have
      significant improvement in symptoms, MGS, TBUT, and Schirmer score, following
      dietary intervention with O3FAs for 6 months.

PMID- 27050030
TI  - Genome-Wide Estimates of Heritability for Social Demographic Outcomes.
AB  - An increasing number of studies that are widely used in the demographic research
      community have collected genome-wide data from their respondents. It is therefore
      important that demographers have a proper understanding of some of the
      methodological tools needed to analyze such data. This article details the
      underlying methodology behind one of the most common techniques for analyzing
      genome-wide data, genome-wide complex trait analysis (GCTA). GCTA models provide
      heritability estimates for health, health behaviors, or indicators of attainment
      using data from unrelated persons. Our goal was to describe this model, highlight
      the utility of the model for biodemographic research, and demonstrate the
      performance of this approach under modifications to the underlying assumptions.
      The first set of modifications involved changing the nature of the genetic data
      used to compute genetic similarities between individuals (the genetic
      relationship matrix). We then explored the sensitivity of the model to
      heteroscedastic errors. In general, GCTA estimates are found to be robust to the
      modifications proposed here, but we also highlight potential limitations of GCTA
      estimates. 

PMID- 27050031
TI  - African Ancestry, Social Factors, and Hypertension Among Non-Hispanic Blacks in
      the Health and Retirement Study.
AB  - The biomedical literature contains much speculation about possible genetic
      explanations for the large and persistent black-white disparities in
      hypertension, but profound social inequalities are also hypothesized to
      contribute to this outcome. Our goal is to evaluate whether socioeconomic status
      (SES) differences provide a plausible mechanism for associations between African
      ancestry and hypertension in a U.S. cohort of older non-Hispanic blacks. We
      included only non-Hispanic black participants (N = 998) from the Health and
      Retirement Study who provided genetic data. We estimated percent African ancestry
      based on 84,075 independent single nucleotide polymorphisms using ADMIXTURE
      V1.23, imposing K = 4 ancestral populations, and categorized into quartiles.
      Hypertension status was self-reported in the year 2000. We used linear
      probability models (adjusted for age, sex, and southern birth) to predict
      prevalent hypertension with African ancestry quartile, before and after
      accounting for a small set of SES measures. Respondents with the highest quartile
      of African ancestry had 8 percentage points' (RD = 0.081; 95% CI: -0.001, 0.164)
      higher prevalence of hypertension compared to the lowest quartile. Adjustment for
      childhood disadvantage, education, income, and wealth explained over one-third
      (RD = 0.050; 95% CI: -0.034, 0.135) of the disparity. Explanations for the
      residual disparity remain unspecified and may include other indicators of SES or
      diet, lifestyle, and psychosocial mechanisms. 

PMID- 27050032
TI  - Social Networks and the Heritability of Migratory Behavior.
AB  - A small but growing body of literature examines the relationship between genetics
      and human migration. These studies suggest that some DRD4 alleles, particularly
      7R+, are related to migration. This is surprising from a sociological
      perspective, which views migration largely as a product of social and economic
      forces. However, social relationships with migrants, which have been theorized to
      influence migration by providing access to migration-specific information and
      resources, can also be viewed as proxies for genetic relatedness within
      households. This study computed intraclass correlations for five relatedness
      groups, along with narrow-sense heritability and environmental correlations,
      using a large survey of Mexicans. Shared and independent variance components were
      estimated using multilevel models for the relatedness groups simultaneously with
      sex and age components. The results indicate that strong environmental influences
      are exerted on young family members and, to a lesser extent, males. On the other
      hand, genetic relatedness plays a large role in determining migration for older
      migrants and females; surprisingly, this is true for both domestic and
      international migrants. 

PMID- 27050033
TI  - Genetic Diversity and Differentiation in Urban and Indigenous Populations of
      Mexico: Patterns of Mitochondrial DNA and Y-Chromosome Lineages.
AB  - Aside from the admixture between indigenous people and people from overseas,
      populations in Mexico changed drastically after the Spanish conquest of the
      sixteenth century, forming an intricate history that has been underutilized in
      understanding the genetic population structure of Mexicans. To infer historical
      processes of isolation, dispersal, and assimilation, we examined the
      phylogeography of mitochondrial (mt) DNA and Y-chromosome lineages in 3,026
      individuals from 10 urban and nine indigenous populations by identifying single
      nucleotide polymorphisms. A geographic array with a predominance of Amerindian
      lineages was observed for mtDNA, with northern indigenous populations being
      divergent from the central and southern indigenous populations; urban populations
      showed low differentiation with isolation by distance. Y-chromosome variation
      distinguished urban and indigenous populations through the Amerindian haplogroup
      Q frequency. The MtDNA and the Y-chromosome together primarily distinguished
      urban and indigenous populations, with different geographic arrays for both. Gene
      flow across geographical distance and between the urban and indigenous realms
      appears to have altered the pre-Hispanic phylogeography in central and southern
      Mexico, mainly by displacement of women, while maintaining the indigenous
      isolation in the north, southeast, and Zapotec regions. Most Amerindian mtDNA
      diversity currently occurs in urban populations and appears to be reduced among
      indigenous people. 

PMID- 27050034
TI  - Estimating Telomere Length Heritability in an Unrelated Sample of Adults: Is
      Heritability of Telomere Length Modified by Life Course Socioeconomic Status?
AB  - Telomere length (TL) is a widely used marker of biological aging and is
      associated with an increased risk of morbidity and mortality. Recently, there has
      been evidence for an association between TL and socioeconomic status (SES),
      particularly for measures of education and childhood SES. Individual differences
      in TL are also influenced by genetic factors, with heritability estimates from
      twin and sibling studies ranging from 34 to 82 percent. Yet the additive
      heritability of TL as a result of measured genetic variations and the extent to
      which heritability is modified by SES is still unknown. Data from the Health and
      Retirement Study, a nationally representative cohort of older adults (mean age 69
      years), were used to provide the first estimates of molecular-based heritability
      of TL using genome-wide complex trait analysis (GCTA). We found that additive
      genetic variance contributed 28 percent (p = .012) of total phenotypic variance
      of TL in the European American sample (n = 3,290). Estimation using the GCTA and
      KING Robust relationship inference methods did not differ significantly in this
      sample. None of the variance from the gene-by-SES interactions examined
      contributed significantly to the total TL variance. Estimation of heritability
      and genetic interaction with SES in the African American sample (n = 442) was too
      unstable to provide reliable estimates. 

PMID- 27050035
TI  - Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal
      Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation
      Example.
AB  - Childhood stressors including physical abuse predict adult cancer risk. Prior
      research portrays this finding as an indirect mechanism that operates through
      coping behaviors, including adult smoking, or through increased toxic exposures
      during childhood. Little is known about potential direct causal mechanisms
      between early-life stressors and adult cancer. Because prenatal conditions can
      affect gene expression by altering DNA methylation, with implications for adult
      health, we hypothesize that maternal stress may program methylation of cancer
      linked genes during gametogenesis. To illustrate this hypothesis, we related
      maternal social resources to methylation at the imprinted MEG3 differentially
      methylated regulatory region, which has been linked to multiple cancer types.
      Mothers (n = 489) from a diverse birth cohort (Durham, North Carolina) provided
      newborns' cord blood and completed a questionnaire. Newborns of currently married
      mothers showed lower (-0.321 SD, p < .05) methylation compared to newborns of
      never-married mothers, who did not differ from newborns whose mothers were
      cohabiting and others (adjusted for demographics). MEG3 DNA methylation levels
      were also lower when maternal grandmothers co-resided before pregnancy (-0.314
      SD, p < .05). A 1-SD increase in prenatal neighborhood disadvantage also
      predicted higher methylation (-0.137 SD, p < .05). In conclusion, we found that
      maternal social resources may result in differential methylation of MEG3, which
      demonstrates a potential partial mechanism priming socially disadvantaged
      newborns for later risk of some cancers. 

PMID- 27050036
TI  - Differential Vulnerability to Early-Life Parental Death: The Moderating Effects
      of Family Suicide History on Risks for Major Depression and Substance Abuse in
      Later Life.
AB  - Only a portion of those individuals exposed to parental death in early life (PDE)
      develop behavioral health disorders. We utilized demographic pedigree data from
      the Utah Population Database to test for differential vulnerability to PDE by
      creating a risk score of familial susceptibility to suicide (FS) at the
      population level. Using logistic panel regression models, we tested for
      multiplicative interactions between PDE and FS on the risks of major depressive
      disorder (MDD) and substance abuse (SA), measured using Medicare claims, after
      age 65. The final sample included 155,983 individuals (born 1886-1944), yielding
      1,431,060 person-years at risk (1992-2009). Net of several potential confounders,
      including probability of survival to age 65, we found an FS * PDE interaction for
      females, in which PDE and FS as main effects had no impact but jointly increased
      MDD risk. No statistically significant main or interactive effects were found for
      SA among females or for either phenotype among males. Our findings are consistent
      with a differential vulnerability model for MDD in females, in which early-life
      stress increases the risk for poor behavioral health only among the vulnerable.
      Furthermore, we demonstrate how demographic and pedigree data might serve as
      tools for investigating differential vulnerability hypotheses. 

PMID- 27050037
TI  - The Geographic Distribution of Genetic Risk as Compared to Social Risk for
      Chronic Diseases in the United States.
AB  - There is an association between chronic disease and geography, and there is
      evidence that the environment plays a critical role in this relationship. Yet at
      the same time, there is known to be substantial geographic variation by ancestry
      across the United States. Resulting geographic genetic variation-that is, the
      extent to which single nucleotide polymorphisms (SNPs) related to chronic disease
      vary spatially-could thus drive some part of the association between geography
      and disease. We describe the variation in chronic disease genetic risk by state
      of birth by taking risk SNPs from genome-wide association study meta-analyses for
      coronary artery disease, diabetes, and ischemic stroke and creating polygenic
      risk scores. We compare the amount of variability across state of birth in these
      polygenic scores to the variability in parental education, own education,
      earnings, and wealth. Our primary finding is that the polygenic risk scores are
      only weakly differentially distributed across U.S. states. The magnitude of the
      differences in geographic distribution is very small in comparison to the
      distribution of social and economic factors and thus is not likely sufficient to
      have a meaningful effect on geographic disease differences by U.S. state. 

PMID- 27050038
TI  - Effectiveness of Chiropractic Care to Improve Sensorimotor Function Associated
      With Falls Risk in Older People: A Randomized Controlled Trial.
AB  - OBJECTIVE: This study assessed whether 12 weeks of chiropractic care was
      effective in improving sensorimotor function associated with fall risk, compared
      with no intervention, in community-dwelling older adults living in Auckland, New
      Zealand. METHODS: Sixty community-dwelling adults older than 65 years were
      enrolled in the study. Outcome measures were assessed at baseline, 4 weeks, and
      12 weeks and included proprioception (ankle joint position sense), postural
      stability (static posturography), sensorimotor function (choice stepping reaction
      time), multisensory integration (sound-induced flash illusion), and health
      related quality of life (SF-36). RESULTS: Over 12 weeks, the chiropractic group
      improved compared with the control group in choice stepping reaction time (119
      milliseconds; 95% confidence interval [CI], 26-212 milliseconds; P = .01) and
      sound-induced flash illusion (13.5%; 95% CI, 2.9%-24.0%; P = .01). Ankle joint
      position sense improved across the 4- and 12-week assessments (0.20 degrees ; 95%
      CI, 0.01 degrees -0.39 degrees ; P = .049). Improvements were also seen between
      weeks 4 and 12 in the SF-36 physical component of quality of life (2.4; 95% CI,
      0.04-4.8; P = .04) compared with control. CONCLUSION: Sensorimotor function and
      multisensory integration associated with fall risk and the physical component of
      quality of life improved in older adults receiving chiropractic care compared
      with control. Future research is needed to investigate the mechanisms of action
      that contributed to the observed changes in this study and whether chiropractic
      care has an impact on actual falls risk in older adults.

PMID- 27050039
TI  - The Supportive Role of Insulin-Like Growth Factor-I in the Differentiation of
      Murine Mesenchymal Stem Cells into Corneal-Like Cells.
AB  - This study was focused on characterizing the differentiation of bone marrow
      derived mesenchymal stem cells (MSCs) into corneal-like cells. Mouse MSCs were
      isolated from the bone marrow, grown in cell culture for 3 weeks, and purified
      using a magnetic activated cell sorter. Purified MSCs were cultured with an
      extract prepared from excised corneas and in the presence or absence of insulin
      like growth factor-I (IGF-I). Analysis by quantitative real-time polymerase chain
      reaction showed that the expression of corneal specific markers, such as
      cytokeratin 12 (K12), keratocan, and lumican, was already induced after a 3-day
      cultivation and gradually increased during the 10-day incubation of MSCs with the
      extract. The presence of IGF-I significantly increased differentiation.
      Immunofluorescence analysis of differentiated MSCs showed positive results for
      the K12 protein. The morphology of the differentiated cells and the expression of
      cell surface markers CD45, CD11b, CD73, CD44, and CD105 were comparable in the
      control and differentiated MSCs. Proliferative activity was even higher in
      differentiated cells than in untreated MSCs. Both untreated and differentiated
      MSCs inhibited the production of interleukin-2 and interferon-gamma in spleen
      cells stimulated with Concanavalin A. The results thus show that MSCs cultured in
      the presence of corneal extract and IGF-I efficiently differentiate into corneal
      like cells. The differentiated cells possess characteristics of corneal
      epithelial cells and keratocytes, while at the same time maintaining MSC
      properties.

PMID- 27050040
TI  - Automated Microscopy: Macro Language Controlling a Confocal Microscope and its
      External Illumination: Adaptation for Photosynthetic Organisms.
AB  - Photosynthesis research employs several biophysical methods, including the
      detection of fluorescence. Even though fluorescence is a key method to detect
      photosynthetic efficiency, it has not been applied/adapted to single-cell
      confocal microscopy measurements to examine photosynthetic microorganisms.
      Experiments with photosynthetic cells may require automation to perform a large
      number of measurements with different parameters, especially concerning light
      conditions. However, commercial microscopes support custom protocols (through
      Time Controller offered by Olympus or Experiment Designer offered by Zeiss) that
      are often unable to provide special set-ups and connection to external devices
      (e.g., for irradiation). Our new system combining an Arduino microcontroller with
      the Cell?Finder software was developed for controlling Olympus FV1000 and FV1200
      confocal microscopes and the attached hardware modules. Our software/hardware
      solution offers (1) a text file-based macro language to control the imaging
      functions of the microscope; (2) programmable control of several external
      hardware devices (light sources, thermal controllers, actuators) during imaging
      via the Arduino microcontroller; (3) the Cell?Finder software with ergonomic user
      environment, a fast selection method for the biologically important cells and
      precise positioning feature that reduces unwanted bleaching of the cells by the
      scanning laser. Cell?Finder can be downloaded from http://www.alga.cz/cellfinder.
      The system was applied to study changes in fluorescence intensity in
      Synechocystis sp. PCC6803 cells under long-term illumination. Thus, we were able
      to describe the kinetics of phycobilisome decoupling. Microscopy data showed that
      phycobilisome decoupling appears slowly after long-term (>1 h) exposure to high
      light. 

PMID- 27050041
TI  - X-Ray Absorption Correction for Quantitative Scanning Transmission Electron
      Microscopic Energy-Dispersive X-Ray Spectroscopy of Spherical Nanoparticles.
AB  - A new method to perform X-ray absorption correction for spherical particles in
      quantitative energy-dispersive X-ray spectroscopy in the scanning transmission
      electron microscope is presented. An absorption correction factor is derived and
      simulated data is presented encompassing a range of X-ray absorption conditions.
      Theoretical calculations are compared with experimental data of X-ray counts from
      Au nanoparticles to verify the derived methodology. The effect of detector
      elevation angle is considered and a comparison with thin-film absorption
      correction is included. 

PMID- 27050042
TI  - Improving therapeutic activity of anti-CD20 antibody therapy through
      immunomodulation in lymphoid malignancies.
AB  - Nearly two decades ago rituximab heralded a new era in management of B cell
      malignancies significantly increasing response rates and survival. However,
      despite clear therapeutic advantage, significant numbers of patients become
      refractory to anti-CD20 mAb therapy, suggesting urgent improvements are required.
      It is now well recognized that the suppressive tumor microenvironment plays an
      important role in the outcome of anti-CD20 mAb therapy and that manipulation of
      this environment may improve the efficacy and produce long-term tumor control.
      The past few years have seen a surge of interest in immunomodulatory agents
      capable of overwriting immune suppressive networks into favorable clinical
      outcome. Currently, a number of such combinations with anti-CD20 mAb is under
      evaluation and some have produced encouraging outcomes in rituximab refractory
      disease. In this review, we give an outline of anti-CD20 mAbs and explore the
      combinations with immunomodulatory agents that enhance antitumor immunity through
      targeting stimulatory or inhibitory pathways and have proven potential to
      synergize with anti-CD20 mAb therapy. These agents, primarily mAbs, target CTLA
      4, PD-1/PD-L1, and CD40.

PMID- 27050043
TI  - Optimal two-stage log-rank test for randomized phase II clinical trials.
AB  - Randomized controlled clinical trials are conducted to determine whether a new
      treatment is safe and efficacious compared to a standard therapy. We consider
      randomized clinical trials with right censored time to event endpoint, called
      survival time here. The two-sample log-rank test is popularly used to test if the
      experimental therapy has a longer survival distribution than the control therapy
      or not. We consider an early stopping for futility only or for both futility and
      efficacy. For planning such clinical trials, this article presents two-stage
      designs that are optimal in the sense that either the maximal sample size or the
      expected sample size when the experimental therapy is futile or superior is
      minimized under the given type I and II error rates. Optimal designs for a range
      of design parameters are tabulated and evaluated using simulations.

PMID- 27050044
TI  - Minimal skin dose increase in longitudinal rotating biplanar linac-MR systems:
      examination of radiation energy and flattening filter design.
AB  - The magnetic fields of linac-MR systems modify the path of contaminant electrons
      in photon beams, which alters patient entrance skin dose. Also, the increased SSD
      of linac-MR systems reduces the maximum achievable dose rate. To accurately
      quantify the changes in entrance skin dose, the authors use EGSnrc Monte Carlo
      calculations that incorporate 3D magnetic field of the Alberta 0.5 T longitudinal
      linac-MR system. The Varian 600C linac head geometry assembled on the MRI
      components is used in the BEAMnrc simulations for 6 MV and 10 MV beam models and
      skin doses are calculated at an average depth of 70 MUm using DOSXYZnrc. 3D
      modeling shows that magnetic fringe fields decay rapidly and are small at the
      linac head. SSDs between 100 and 120 cm result in skin-dose increases of between
      ~6%-19% and ~1%-9% for the 6 and 10 MV beams, respectively. For 6 MV, skin dose
      increases from ~10.5% to ~1.5% for field-size increases of 5  *  5 cm(2) to 20  *
      20 cm(2). For 10 MV, skin dose increases by ~6% for a 5  *  5 cm(2) field, and
      decreases by ~1.5% for a 20  *  20 cm(2) field. Furthermore, the proposed
      reshaped flattening filter increases the dose rate from the current 355 MU min(
      1) to 529 MU min(-1) (6 MV) or 604 MU min(-1) (10 MV), while the skin-dose
      increases by only an additional ~2.6% (all percent increases in skin dose are
      relative to D max). This study suggests that there is minimal increase in the
      entrance skin dose and minimal/no decrease in the dose rate of the Alberta
      longitudinal linac-MR system. The even lower skin dose increase at 10 MV offers
      further advantages in future designs of linac-MR prototypes.

PMID- 27050045
TI  - Yoga Therapy for Abdominal Pain-Related Functional Gastrointestinal Disorders in
      Children: A Randomized Controlled Trial.
AB  - OBJECTIVES: The aim of the present study was to compare effects of 10 weeks of
      yoga therapy (YT) and standard medical care (SMC) on abdominal pain and quality
      of life (QoL) in children with abdominal pain-related functional gastrointestinal
      disorders (AP-FGIDs). METHODS: Sixty-nine patients, ages 8 to 18 years, with AP
      FGIDs, were randomized to SMC complemented with YT or SMC alone. YT is a mixture
      of yoga poses, meditation, and relaxation exercises and was given once a week in
      group sessions. SMC consisted of education, reassurance, dietary advice, and
      fibers/mebeverine, if necessary. Pain intensity (pain intensity score [PIS] 0-5)
      and frequency (pain frequency score [PFS] 0-4) were scored in a pain diary, and
      QoL was measured with KIDSCREEN-27. Follow-up was 12 months. Treatment response
      was defined as >=50% reduction of weekly pain scores. RESULTS: At 1-year follow
      up, treatment response was accomplished in 58% of the YT group and in 29% of the
      control group (P = 0.01); no significant differences for other time points were
      found. YT, and not SMC, resulted in a significant reduction of PIS (P < 0.01) and
      PFS (P < 0.01) after 12 months. During the study, however, YT was not
      significantly superior compared with SMC. Subanalyses for time points
      demonstrated a significant greater reduction of PIS at 12 months in favor of YT.
      No differences were found for QoL. YT was more effective in the reduction of
      reported monthly school absence (P = 0.03). CONCLUSION: At 1-year follow-up, YT
      in addition to standard care was superior compared with SMC according to
      treatment success, PIS, and reduction of school absence. YT, however, was not
      significantly more effective in improving PFS or QoL, compared with SMC.

PMID- 27050046
TI  - CT and MRI of Rare Extraintestinal Manifestations of Inflammatory Bowel Disease
      in Children and Adolescents.
AB  - Inflammatory bowel disease (IBD) is associated with a spectrum of extraintestinal
      manifestations (EIMs) affecting many organ systems. EIMs can occur in more than
      40% of patients with IBD and are associated with significant morbidity. They
      occur at any time point in the course of disease, often during an active phase of
      bowel inflammation, but sometimes preceding bowel disease. Prompt recognition of
      EIMs enables timely and more effective therapy. Physicians who image patients
      with IBD should be aware of the myriad extraintestinal conditions that may be
      detected on imaging studies, both within and outside of the abdomen, as they may
      predate the diagnosis of IBD. Cross-sectional imaging of unusual conditions
      associated with IBD will be presented, including pathology in the hepatobiliary,
      pancreatic, genitourinary, musculoskeletal, mucocutaneous, vascular, neurologic,
      and pulmonary systems.

PMID- 27050047
TI  - Chronic Recurrent Multifocal Osteomyelitis in Crohn Disease: Complete Resolution
      With Anti-TNFalpha Therapy.

PMID- 27050048
TI  - Hepatitis E in Children: A Position Paper by the ESPGHAN Hepatology Committee.
AB  - BACKGROUND: Hepatitis E virus (HEV) is endemic in large parts of the developing
      world. Waterborne transmission of genotypes 1 or 2 commonly causes acute
      hepatitis, which is usually self-limited in healthy individuals. In addition,
      acute HEV infections also occur outside endemic areas, mostly related to
      foodborne transmission of HEV genotype 3. A growing number of publications in the
      last decade have reported chronic infection progressing to cirrhosis in
      immunosuppressed patients. It has also been suggested that HEV transmission may
      occur via contaminated blood products. This publication aims to provide
      recommendations for diagnosis, prevention, and treatment of HEV infection,
      particularly in children after solid organ transplantation. METHODS: A systematic
      PubMed literature search on HEV infection from 1990 to January 2016 was performed
      focusing on pediatric studies. The existing body of evidence was reviewed and
      recommendations were agreed upon following discussion and unanimous agreement by
      all members of the ESPGHAN Hepatology Committee during a consensus meeting in
      January 2016. In the absence of randomized controlled studies these
      recommendations were considered to be expert opinions. KEY RECOMMENDATIONS:
      Immunocompetent children with increased transaminases and/or extrahepatic
      manifestations should be considered for testing for evidence of HEV infection.
      Immunocompromised children with increased aminotransferases should be repeatedly
      tested for HEV and may require therapeutic intervention.

PMID- 27050049
TI  - Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper
      by the ESPGHAN Committee on Nutrition.
AB  - Vitamin K deficiency bleeding (VKDB) due to physiologically low vitamin K plasma
      concentrations is a serious risk for newborn and young infants and can be largely
      prevented by adequate vitamin K supplementation. The aim of this position paper
      is to define the condition, describe the prevalence, discuss current prophylaxis
      practices and outcomes, and to provide recommendations for the prevention of VKDB
      in healthy term newborns and infants. All newborn infants should receive vitamin
      K prophylaxis and the date, dose, and mode of administration should be
      documented. Parental refusal of vitamin K prophylaxis after adequate information
      is provided should be recorded especially because of the risk of late VKDB.
      Healthy newborn infants should either receive 1 mg of vitamin K1 by intramuscular
      injection at birth; or 3 * 2 mg vitamin K1 orally at birth, at 4 to 6 days and at
      4 to 6 weeks; or 2 mg vitamin K1 orally at birth, and a weekly dose of 1 mg
      orally for 3 months. Intramuscular application is the preferred route for
      efficiency and reliability of administration. The success of an oral policy
      depends on compliance with the protocol and this may vary between populations and
      healthcare settings. If the infant vomits or regurgitates the formulation within
      1 hour of administration, repeating the oral dose may be appropriate. The oral
      route is not appropriate for preterm infants and for newborns who have
      cholestasis or impaired intestinal absorption or are too unwell to take oral
      vitamin K1, or those whose mothers have taken medications that interfere with
      vitamin K metabolism. Parents who receive prenatal education about the importance
      of vitamin K prophylaxis may be more likely to comply with local procedures.

PMID- 27050050
TI  - Which PCDAI Version Best Reflects Intestinal Inflammation in Pediatric Crohn
      Disease?
AB  - INTRODUCTION: There is increasing interest in measuring mucosal inflammation in
      Crohn disease (CD), but there are minimal data correlating the Pediatric Crohn's
      Disease Activity Index (PCDAI) versions (PCDAI, weighted Pediatric Crohn's
      Disease Activity Index [wPCDAI], abbreviated Pediatric Crohn's Disease Activity
      Index [abbrPCDAI], and the short Pediatric Crohn's Disease Activity Index
      [shPCDAI]) with mucosal inflammation. METHODS: We aimed to compare the 4 PCDAI
      versions head to head with endoscopic degree of inflammation as measured by the
      Simple Endoscopic Score for Crohn's Disease (SES-CD), fecal calprotectin,
      erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and to explore
      cut-off values that are associated with mucosal healing. We used the
      prospectively collected data from the ImageKids study on 100 children with CD
      undergoing colonoscopy and from the Growth Relapse and Outcomes with Therapy
      study (n = 222), in which 145 children had calprotectin data at week 12 after
      diagnosis. RESULTS: All 4 PCDAI versions had fair correlation with the SES-CD (r
      = 0.42-0.45, all P < 0.001) and CRP (r = 0.32-0.45, all P < 0.01); the wPCDAI and
      PCDAI were superior to the shorter versions when comparing the blood tests. All
      versions had poor correlation with calprotectin, and only the wPCDAI reached
      significance (r = 0.26, P = 0.002 vs r = 0.15, P = 0.07 for PCDAI; r = 0.08, P =
      0.37 for shPCDAI; r = 0.06, P = 0.5 for abbrPCDAI). The best cut-off to identify
      endoscopic mucosal healing was <12.5 points for the wPCDAI (sensitivity 58% and
      specificity 84%) and <10 for PCDAI (sensitivity 63% and specificity 77%).
      CONCLUSIONS: The more feasible wPCDAI and the PCDAI had comparable correlation
      with measures of endoscopic inflammation. These were slightly superior to the
      other 2 shorter versions, but still none of the PCDAI versions can give a valid
      assessment of mucosal healing.

PMID- 27050051
TI  - Pneumatosis Coli in Complex Neurodisability: An Increasingly Problematic Disease
      Spectrum and Proposed Management.
AB  - This case series describes our experience in managing 4 children with complex
      neurodisability, feed intolerance, and pneumatosis coli. In all of the 4
      patients, symptoms and feed tolerance were substantially improved by the
      formation of a laparoscopically assisted defunctioning ileostomy. We describe our
      present management strategy and believe this is a promising treatment for those
      patients who can reduce long-term dependence on parenteral nutrition, although we
      acknowledge that there is a long-term risk of disuse colitits in the defunctioned
      bowel.

PMID- 27050052
TI  - Carcinoid Tumor Complicating Crohn Disease in a Female Adolescent.

PMID- 27050053
TI  - Accuracy of Prediction Formulae for the Assessment of Resting Energy Expenditure
      in Hospitalized Children.
AB  - BACKGROUND AND AIM: The resting energy expenditure (REE) of ill children is
      commonly estimated from prediction formulae developed in healthy children. The
      aim of the present study was to evaluate the accuracy of commonly employed REE
      prediction formulae versus indirect calorimetry in hospitalized children.
      METHODS: We performed a cross-sectional study of 236 infants, children, and
      adolescents consecutively admitted to the Intermediate Care, Nephrology,
      Intensive Care, Emergency, and Cystic Fibrosis Units of the De Marchi Pediatric
      Hospital (Milan, Italy) between September 2013 and March 2015. REE was measured
      by indirect calorimetry and estimated using the World Health Organization (WHO),
      Harris-Benedict, Schofield, and Oxford formulae. RESULTS: The mean (standard
      deviation) difference between the estimated and measured REE was: -1 (234)
      kcal/day for the WHO formula; 82 (286) kcal/day for the Harris-Benedict formula;
      2 (215) kcal/day for the Schofield-weight formula; -2 (214) kcal/day for the
      Schofield-weight and height formula; and -5 (221) kcal/day for the Oxford
      formula. Even though the WHO, Schofield, and Oxford formulae gave accurate
      estimates of REE at the population level (small mean bias), all the formulae were
      not accurate enough to be employed at the individual level (large SD of bias).
      CONCLUSIONS: The WHO, Harris-Benedict, Schofield, and Oxford formulae should not
      be used to estimate REE in hospitalized children.

PMID- 27050054
TI  - More Than Just the Delivery.

PMID- 27050055
TI  - Ascites in Children: A Single-Center Experience of 27 Years.
AB  - OBJECTIVES: The aim of our study was to describe the changing prevalence,
      demographic features, etiologies, and treatment of ascites in children
      hospitalized during a 27-year period at the Johns Hopkins Hospital (Baltimore,
      MD). METHODS: We retrospectively reviewed discharges from 1983 to 2010 to select
      patients whose records included a diagnosis of ascites. We assessed the
      etiologies and degrees of ascites (ascites grade 1 detectable only by radiologic
      tests; ascites grades 2 and 3 recognized by moderate and marked abdominal
      distension by physical examinations). RESULTS: We classified 518 children into 9
      etiology groups: intrahepatic disease (IH) (105), hepatic vein outflow
      obstruction (HVOO) (45), congestive heart disease (CH) (33), nephrotic syndrome
      (NS) (36), pancreatitis (26), inflammatory and infectious diseases (77),
      malignancy (49), idiopathic (71), and miscellaneous (76). IH and CH were
      predominant in the younger age group (0-5 years) versus HVOO, pancreatitis, and
      malignancy in the older age group (13-21 years) (P < 0.001). The prevalence of
      ascites increased over time from 1983 to 2006 and declined thereafter. Ascites
      grade 1 was more common than ascites grades 2 and 3 in all the groups (P =
      0.048). IH and NS were more likely to have ascites grade 2 and 3 (P = 0.02).
      Although spironolactone was more frequently used in the IH group versus other
      etiologies, furosemide was used more frequently in NS and CH versus other
      etiologies (P < 0.001). CONCLUSIONS: The increased prevalence of ascites during
      the initial study period could reflect improved detection radiologic detection.
      The proportion of severe ascites and the various medical treatments differed
      among the etiologic groups.

PMID- 27050056
TI  - Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A
      Randomized Placebo-Controlled Trial.
AB  - Pancreatic enzyme therapy does not normalize dietary fat absorption in patients
      with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS),
      an easily absorbable lipid matrix that enhances fat absorption, was evaluated in
      a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty
      acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110
      subjects (age 10.4 +/- 3.0 years) were randomized. Total FA increased with LXS at
      3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS,
      linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P <= 0.046),
      with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus
      placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased
      body mass index Z scores. In summary, the LXS treatment improved dietary fat
      absorption compared with placebo as indicated by plasma FA and LA and was
      associated with better growth status.

PMID- 27050057
TI  - Baseline Wall Thickness Is Lower in Mucosa-Healed Segments 1 Year After
      Infliximab in Pediatric Crohn Disease Patients.
AB  - OBJECTIVES: We aimed to quantitatively investigate the therapeutic response to
      combined immunosuppression treatment by magnetic resonance enterography (MRE) in
      active luminal Crohn disease (CD) in the pediatric population. METHODS: Pediatric
      patients with moderate-to-severe luminal CD, who received scheduled infliximab
      and azathioprine, were included in this preliminary study. Ileocolonoscopy and
      MRE were performed at baseline and at 1 year, and Simple Endoscopic Score for
      Crohn's Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) scores
      were calculated. The correlation between SES-CD and MaRIA scores were
      investigated with analysis per person and per segment. RESULTS: A total of 167
      segments from 17 patients were evaluated by both Ileocolonoscopy and MRE. SES-CD
      and MaRIA scores showed significant correlations on both per-person analysis (rho
      = 0.699, P < 0.001) and per-segment analysis (rho = 0.596, P < 0.001). Analysis
      according to ileocolonic location of each segment revealed that the correlation
      strength was strongest in the right colon (rho = 0.653, P < 0.001), whereas the
      correlation in the rectum was statistically insignificant (rho = 0.29, P =
      0.096). A comparative analysis of MaRIA components revealed a significantly
      thinner bowel wall thickness at baseline in endoscopically healed segments
      (50/65) compared with unhealed segments (15/65) (median 4.3 vs 7.2 mm, P =
      0.036). CONCLUSIONS: Therapeutic response to combined immunosuppression at 1 year
      assessed by MRE correlates with ileocolonoscopy in pediatric patients with CD.
      Bowel wall thickness of the involved segments at baseline may affect treatment
      response to combined immunosuppression.

PMID- 27050058
TI  - Coagulation Gene Expression Profiling in Infants With Necrotizing Enterocolitis.
AB  - OBJECTIVES: Coagulopathy and mesenteric thrombosis are common in premature
      neonates with necrotizing enterocolitis (NEC). This pilot study aimed to
      investigate the hypothesis that there are changes in the gene expression related
      to the coagulation and anticoagulation systems in NEC. METHODS: Consecutive
      neonates (n = 11) with NEC (Bell stages 2-3) were recruited. Two comparison
      groups, matched for birth weight and corrected gestational age, were selected
      based on the absence of inflammation and coagulopathy (healthy control, n = 10),
      or the presence of a confirmed blood infection (sepsis control, n = 12). A
      pathway-specific quantitative polymerase chain reaction array was used to
      determine the expression of 94 genes involved in human blood coagulation and
      anticoagulation cascade. RESULTS: Twelve genes of the coagulation and
      anticoagulation systems were significantly altered in the patients with NEC
      compared with healthy controls. In particular, neutrophil elastase, CD63, PROS1,
      HGF, and F12 were significantly upregulated (mean fold changes [FCs] +2.74, P <
      0.05) with an overall procoagulant effect; MFGE8, factor II (thrombin) receptor
      like 1 (F2RL1), FGL2, PLAT, PROCR, SERPIND1, and HNF4A were significantly
      downregulated (mean FCs -2.45, P < 0.05) with a reduction in fibrinolysis and
      endothelial regeneration. In the comparison between NEC and sepsis, we did
      observe a significant difference in expression of F2RL1 (FC -2.50, P = 0.01).
      CONCLUSIONS: We have identified potential biomarkers associated with coagulopathy
      and disease progression in NEC. In particular, the overall procoagulant status,
      at the transcriptional level, should be further investigated to unveil molecular
      mechanisms leading to intestinal necrosis, multiorgan failure, and death.

PMID- 27050060
TI  - Relationship between the Level of Education and Functional Capacity in Active
      Elderly Adults.
AB  - BACKGROUND: Both the level of education and functional capacity seems to be
      associated with the level of physical activity in the elderly. However, the
      relationship between the level of education and functional capacity in active
      elderly adults is poorly understood. OBJECTIVE: To examine the association
      between the level of education and the functional capacity profile of active
      elderly adults. DESIGN: Cross-sectional. PARTICIPANTS: One hundred and four
      elderly men and 198 postmenauposal women (mean age: 62.7 +/- 7.6 years old) were
      recruited among registered members of the YMCAs of Montreal who practiced at
      least one hour of structured physical activity per week. Participants were then
      divided in two groups based on their level of education (the cut-off point was
      the high-school diploma). MEASUREMENTS: Body composition (DXA), muscle strength
      (knee extensors, handgrip), estimated maximal oxygen consumption (2-km walk
      test), perceived health (SF-36) and functional capacity (timed up and go,
      alternate step and one-leg stance tests) were measured. The level of education of
      the participants was assessed by questionnaire. RESULTS: Body composition was
      similar between groups. We observed that all functional capacity tests as well as
      the global functional capacity score were significantly higher in the most
      educated group compared to the least educated group (p<0.05). In addition, the
      most educated group had significantly higher levels of knee extensors strength,
      estimated maximal oxygen consumption and perception of physical functioning.
      CONCLUSIONS: A higher level of education was associated with a favourable
      functional capacity profile in our cohort of active elderly adults. However, the
      mechanism(s) which could mediate this association remain(s) unknown.

PMID- 27050059
TI  - A New Grip Strength Measuring Device for Detailed Evaluation of Muscle
      Contraction among the Elderly.
AB  - BACKGROUND: We developed a new grip strength measuring device, which considers
      the time axis, for evaluating muscle contraction in detail in elderly people.
      OBJECTIVES: To present the novel device and preliminary results concerning
      agility in gripping. DESIGN: Cross-sectional analysis. PARTICIPANTS: One hundred
      and twenty-one older persons (48 men and 73 women, mean age 74.4 years) referring
      for memory disorders to the outpatient clinic of our institute. MEASUREMENTS: A
      novel device taking advantage of an industrial force-gauge was developed for
      measuring gripping performance. The instrument graphically described
      participants' strength production. Nine indices were derived from four points
      identified by the graph: 1) starting point ("Go signal"), 2) time when gripping
      starts, 3) turning point (TP) when the inclination of the curve depicting
      strength production changes, and 4) peak of strength production. Results obtained
      from the study sample of older persons were compared (as ratios) to a control
      group of 30 healthy young adults in their thirties in order to calculate age
      related decline rates. Differences between right and left side were compared.
      RESULTS: A significant difference was observed between right and left hands
      concerning the time to reach peak of strength, and time from TP to strength peak
      in both men and women. For women, the following indices were also significantly
      different: time to reach TP, strength at TP, time from TP to strength peak, curve
      inclination from TP to strength peak, and ratio of TP strength divided by peak
      strength. CONCLUSION: Declines in several indices of gripping agility were
      measured. The parameters which were more closely related to time than strength
      itself showed significant differences between right and left hands, especially in
      women.

PMID- 27050061
TI  - Relationship between Frailty and Cognitive Function among Older Adults in Taiwan.
AB  - BACKGROUND: The causal relationship between physical frailty and cognitive
      function is not yet completely confirmed. OBJECTIVES: This study aimed at
      exploring the reciprocal relationship of frailty and cognitive function among
      Taiwanese older adults. PARTICIPANTS AND SETTING: The study evaluated data from a
      five-wave survey conducted in Taiwanese older persons (n=3,155 respondents,
      10,631 observations). MEASUREMENTS: Frailty was defined as low physical activity,
      exhaustion, poor appetite, poor grip strength, and difficulty in carrying 10
      pound objects; individuals were defined as frail if they met three or more of the
      above criteria. Cognitive function was assessed using five items from the Short
      Portable Mental Status Questionnaire (SPMSQ) scale. Time-lagged and time
      concurrent models were performed to examine the reciprocal relationship between
      cognitive function and frailty. Growth-curve hierarchical linear modeling was
      applied. RESULTS: Concurrent frailty was related to low cognitive function at the
      intercept and time slope and vice versa. Previous frailty also predicted later
      decline of cognitive function. Nevertheless, previous cognitive function was not
      found to have a significant relationship with subsequent frailty. Education,
      physical function and social support represented shared factors to both frailty
      and cognitive function. CONCLUSIONS: Frailty and cognitive function are
      correlated, and frailty may occur prior to cognitive impairment.

PMID- 27050062
TI  - Frailty and Pre-Frailty in a Contemporary Cohort of HIV-Infected Adults.
AB  - OBJECTIVES: To determine the prevalence of pre-frailty among HIV-infected persons
      and associations with pre-frailty and frailty in this population. DESIGN, SETTING
      AND PARTICIPANTS: From a contemporary, prospective observational cohort of HIV
      infected persons (SUN Study), we determined, using a cross-sectional analytic
      study design, the proportions of non-frail, pre-frail, and frail persons by the
      respective presence of 0, 1-2, and >= 3 of 5 established frailty criteria:
      unintentional weight loss, exhaustion, physical-inactivity, weak-grip and slow
      walk. We evaluated associations with pre-frailty/frailty using multivariate
      analysis. RESULTS: Of 322 participants assessed (79% men, 58% white non-Hispanic,
      median age 47 years, 95% on combination antiretroviral therapy [cART], median CD4
      + cell count 641 cells/mm3 and 93% HIV RNA < 400 copies/mL), 57% were non-frail,
      38% pre-frail, and 5% frail. Age increased from non-frailty through frailty.
      Notably, however, half of pre-frail and frail participants were < 50 years, and
      of those, 42% and 100%, respectively, were long-term unemployed (versus 16% of
      non-frail counterparts). In multivariate analysis, pre-frail/frail participants
      were more likely to have Hepatitis C seropositivity (adjusted odds ratio [aOR]
      3.24, 95% CI: 1.35-7.78), a history of AIDS-defining-illness (aOR 3.51, 95% CI:
      1.82-6.76), greater depressive symptoms (aOR 1.16, 95% CI:1.09-1.23), higher D
      dimer levels (aOR 2.94, 95% CI:1.10-7.87), and were less likely to be white non
      Hispanic (aOR 0.35, 95% CI: 0.20-0.61). CONCLUSIONS: Pre-frailty and frailty are
      prevalent in the cART era and are associated with unemployment even among persons
      < 50 years. Pre-frailty appears to be an intermediate state in the spectrum from
      non-frailty through frailty and our characterization of pre-frailty/frailty
      suggests complex multifactorial associations.

PMID- 27050063
TI  - Associations between Frailty, Complex Care Needs and Quality of Life in Multi
      Morbid Older People.
AB  - BACKGROUND: Little is known regarding the complex care needs, level of frailty or
      quality of life of multi-morbid older patients. OBJECTIVES: The objective of this
      study was to determine the relationship between frailty, complexity of care and
      quality of life in multi-morbid older people. DESIGN: Cross-sectional study.
      SETTING: Thirteen primary care practices in the Netherlands. PARTICIPANTS: 1,150
      multi-morbid older people living in the community. MEASUREMENTS: The level of
      frailty was assessed with the Groningen Frailty Indicator. Complexity of care
      needs was measured with the Intermed for the Elderly Self-Assessment. Quality of
      life (QoL) was measured with two items of the RAND-36. RESULTS: In total, 758 out
      of 1,150 (65.9%) patients were frail, 8.3% had complex care needs, and the mean
      QoL score was 7.1 (standard deviation 1.2). Correlations between frailty and
      complexity, frailty and QoL, and complexity of care and QoL were 0.67, -0.51 and 
      0.52 (all p<0.001) respectively. All patients with complex care needs were frail,
      but, only 12.5% of the frail patients had complex care needs. Problems at
      climbing up stairs was associated with higher levels of frailty and complexity of
      care but with a lower QoL. CONCLUSIONS: Higher levels of frailty and complexity
      of care are associated with a lower QoL in multi-morbid older people. The results
      of this study contribute to a better understanding these concepts and are
      valuable for the development of tailored interventions for older persons in the
      future.

PMID- 27050064
TI  - Is the Latin American and Caribbean Food Security Scale an Appropriate Instrument
      for Mexican Urban Older Adults?
AB  - BACKGROUND: Older adults in Mexico are a growing share of the population and are
      a largely vulnerable group with increased risk of food insecurity and potential
      detrimental health effects stemming from it. OBJECTIVES: This study assesses the
      face validity of the Latin American and Caribbean Food Security Scale (ELCSA)
      among Mexican urban older adults of low socioeconomic status. DESIGN: Qualitative
      study based on 4 focus groups. SETTING: The focus groups were conducted in
      community organizations for the elderly in an area of Mexico City with a high
      proportion of poverty. PARTICIPANTS: The focus groups included a total of 36
      older adults aged 65 and over who consented to participate. MEASUREMENTS: Two
      initial focus groups were conducted to assess how older adults understood the
      food security construct and each of the ELCSA items. Based on these findings,
      ELCSA was modified and retested for face validity through two additional focus
      groups. RESULTS: The initial focus groups suggested that several of the scale
      items were not well understood, leading to editorial modifications of the scale.
      The final focus groups indicated that the modified version of the scale improved
      substantially ELCSA's face validity in this sample. CONCLUSIONS: The modified
      ELCSA led to a greater understanding of most scale items. Further qualitative
      research is needed to improve food insecurity measurements among older adults in
      Latin America.

PMID- 27050065
TI  - Frailty from an Oral Health Point of View.
AB  - Frailty commonly affects older persons, increasing their risk for adverse
      outcomes. Oral health is affected by those conditions related to the mouth and
      teeth, including caries, periodontal diseases, dysgeusia, presbyphagia and oral
      cancer among others. Oral health problems can be classified as development
      defects and acquired problems. These latter are related to infection or trauma,
      have a cumulative effect throughout life and their consequences are lifelong.
      Such acquired problems can be classified as primary or secondary, both
      interacting in a complex manner. Recovery to a previous state of tissue integrity
      is often impossible from these conditions. These complex interactions have
      negative impacts on the individual's general health and quality of life. Oral
      status is an important contributor to general health, and has been linked to
      several chronic conditions such as cognitive impairment, diabetes, cardiovascular
      diseases, strokes, and cancer. An individual's oral health is mostly stable
      throughout life. Tooth loss may be considered as the final outcome, resulting as
      a consequence of history of caries and periodontitis, as well as failure of
      prevention and treatment. The loss of a tooth may thus represent the first step
      of a vicious cycle. In fact, without intervention, one missing tooth may lead to
      further teeth loss, thus reducing the capability to chew and consume nutrients
      (essential for life and adequate physiological function), and finally
      contributing to the development of age-related chronic diseases. 

PMID- 27050066
TI  - Letter to the Editor: How Useful Are Multidomain Frailty Measures in Research and
      Clinical Practice?

PMID- 27050067
TI  - Tale of 2 Agencies: CDC Avoids Gun Violence Research But NIH Funds It.

PMID- 27050068
TI  - Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on
      Inflammatory Response in Brain Dead Organ Donors.
AB  - BACKGROUND: Brain death is a major stress that is associated with a massive
      inflammatory response and systemic hyperglycemia. Severe inflammation leads to
      increased graft immunogenicity and risk of graft dysfunction; while acute
      hyperglycemia aggravates the inflammatory response and increases the risk of
      morbidity and mortality. Insulin therapy not only controls hyperglycemia but also
      suppresses inflammation. The present study is to investigate the anti
      inflammatory properties and the normoglycemia maintenance of high dose insulin on
      brain dead organ donors. DESIGN: 15 brain dead organ donors were divided into 2
      groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a
      minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The
      changes of serum cytokines, including IL-6, IL-10, IL-1beta, IL-8, TNFalpha,
      TGFalpha and MCP-1, were measured by suspension bead array immunoassay and
      glucose by a glucose monitor. RESULTS: Compared to controls, insulin treated
      donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L,
      p<0.01); the net decreases of pro-inflammatory cytokines, such as IL-6 and MCP-1,
      and the net increase of anti-inflammatory cytokine, such as IL-10, reached
      significant level in insulin treated donors compared with those in controls.
      CONCLUSION: High dose insulin therapy decreases the concentrations of
      inflammatory cytokines in brain dead donors and preserves normoglycemia. High
      dose of insulin may have anti-inflammatory effects in brain dead organ donors and
      therefore, improve the quality of donor organs and potentially improve outcomes.

PMID- 27050069
TI  - A Diabetes-specific Oral Nutritional Supplement Improves Glycaemic Control in
      Type 2 Diabetes Patients.
AB  - AIMS: Reducing the intake of low molecular weight carbohydrates with artificial
      nutrition may lower glycaemic response in patients with diabetes. We evaluated
      effects of a diabetes-specific carbohydrate modified oral nutritional supplement
      (ONS) during 12 weeks administration in 40 elderly type 2 normal weight patients
      with diabetes with previous involuntary weight loss. METHODS: Prospective,
      randomised, double-blind, controlled trial. Patients ingested 2*200 ml/day
      diabetes-specific or isocaloric standard ONS (control) in addition to their
      regular diet. Parameters of glucose and lipid metabolism, functional and
      nutritional status were assessed at baseline, weeks 6 and 12. RESULTS:
      Postprandial glucose incremental area under the curve (iAUC0-240 min) was
      comparable between treatment groups on day 1 (467.9+/-268.4 vs. 505.1+/-206.1
      mmol/l*min, n.s. - arithmetic means+/-standard deviation) and was significantly
      lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (355.2+/
      115.8 vs. 634.9+/-205.9 and 364.9+/-153.1 vs. 743.4+/-202.7; both P<0.0001).
      Postprandial peak glucose was significantly lower with the diabetes-specific ONS
      vs. controls in weeks 6 and 12 (P<0.0001) and the decrease in HbA1c, (baseline to
      week 12) was markedly pronounced (P=0.028). There were no differences between
      groups in insulin, HOMA-IR, lipid parameters, nutritional and performance status.
      Body weight and body mass index (BMI) increased significantly over time in both
      groups. CONCLUSIONS: Administration of a diabetes-specific ONS for 12 weeks
      reduced postprandial glycaemia after ingestion of the study treatment and
      improved long-term glycaemic control in elderly patients with type 2 diabetes and
      involuntary weight loss, thereby reducing their risk for diabetes-associated long
      term complications.

PMID- 27050070
TI  - Arterial Stiffness, BMI, Dipping Status and ACE D/I Polymorphism in Type 1
      Diabetic Children.
AB  - THE AIM: of the study was to investigate clinical and genetic determinants of
      arterial stiffness in children and adolescents with type 1 diabetes mellitus.
      MATERIAL AND METHODS: 122 patients (mean age: 16.0+/-2.35 years), with an average
      diabetes duration of 5.0 years and without evidence of arterial hypertension were
      recruited. Ambulatory arterial stiffness index (AASI) was assessed with 24-h
      automatic blood pressure monitoring. Body weight, height, HbA1c and plasma lipids
      were measured. Angiotensin I converting enzyme (ACE) gene insertion (I)/deletion
      (D) polymorphism was analysed. RESULTS: Mean AASI equalled 0.22+/-0.20 and showed
      significant, positive correlation with age and BMI-SDS. No association was found
      between AASI and gender, diabetes duration, daily insulin dose, HbA1c and blood
      lipids concentration. AASI was higher in non-dippers compared to dippers (0.26+/
      0.18 vs. 0.19+/-0.18, respectively; p=0.04). In a multivariate model AASI was
      significantly associated with II homozygosity of ACE gene (p=0.007). CONCLUSIONS:
      In type 1 diabetic children and adolescents AASI is correlated with age and BMI
      SDS. Non-dipping status and I-allele were associated with higher arterial
      stiffness.

PMID- 27050071
TI  - TR4 nuclear receptor enhances the cisplatin chemo-sensitivity via altering the
      ATF3 expression to better suppress HCC cell growth.
AB  - Early studies indicated that TR4 nuclear receptor (TR4) may play a key role to
      modulate the prostate cancer progression, its potential linkage to liver cancer
      progression, however, remains unclear. Here we found that higher TR4 expression
      in hepatocellular carcinoma (HCC) cells might enhance the efficacy of cisplatin
      chemotherapy to better suppress the HCC progression. Knocking down TR4 with TR4
      siRNA in HCC Huh7 and Hep3B cells increased cisplatin chemotherapy resistance and
      overexpression of TR4 with TR4-cDNA in HCC LM3 and SNU387 cells increased
      cisplatin chemotherapy sensitivity. Mechanism dissection found that TR4 might
      function through altering the ATF3 expression at the transcriptional level to
      enhance the cisplatin chemotherapy sensitivity, and interrupting ATF3 expression
      via ATF3-siRNA reversed TR4-enhanced cisplatin chemotherapy sensitivity in HCC
      cells. The in vivo HCC mouse model using xenografted HCC LM3 cells also confirmed
      in vitro cell lines data showing TR4 enhanced the cisplatin chemotherapy
      sensitivity. Together, these results provided a new potential therapeutic
      approach via altering the TR4-ATF3 signals to increase the efficacy of cisplatin
      to better suppress the HCC progression. 

PMID- 27050072
TI  - A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1
      for breast cancer brain metastases.
AB  - Breast cancer brain metastases (BCBMs) are common in patients with metastatic
      breast cancer and indicate a poor prognosis. These tumors are especially
      resistant to currently available treatments due to multiple factors. However, the
      combination of chimeric antigen receptor (CAR)-modified immune cells and
      oncolytic herpes simplex virus (oHSV) has not yet been explored in this context.
      In this study, NK-92 cells and primary NK cells were engineered to express the
      second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells,
      oHSV-1, and their combination were tested in vitro and in a breast cancer
      intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or
      primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed
      enhanced cytotoxicity and IFN-gamma production when co-cultured with breast
      cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also
      capable of lysing and destroying these cells. However, a higher cytolytic effect
      of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the
      monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA
      MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92
      cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK
      92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells
      and significantly longer survival of tumor-bearing mice when compared to
      monotherapies. These results demonstrate that regional administration of EGFR-CAR
      NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to
      treat BCBMs. 

PMID- 27050073
TI  - Lysyl oxidase family activity promotes resistance of pancreatic ductal
      adenocarcinoma to chemotherapy by limiting the intratumoral anticancer drug
      distribution.
AB  - Solid tumors often display chemotherapy resistance. Pancreatic ductal
      adenocarcinoma (PDAC) is the archetype of resistant tumors as current
      chemotherapies are inefficient. The tumor stroma and extracellular matrix (ECM)
      are key contributors to PDAC aggressiveness and to limiting the efficacy of
      chemotherapy. Lysyl oxidase (LOX) family members mediate collagen cross-linking
      and thus promote ECM stiffening. Our data demonstrate increased LOX, LOXL1, and
      LOXL2 expression in PDAC, and that the level of fibrillar collagen, which is
      directly dependent of LOX family activity, is an independent predictive biomarker
      of adjuvant "Gemcitabine-based chemotherapy" benefit. Experimentally in mice,
      increased LOX family activity through LOXL2 promotes chemoresistance. This effect
      of LOX family activity seems to be due to decreased gemcitabine intra-tumoral
      diffusion. This observation might be explained by increased fibrillar collagen
      and decreased vessel size observed in tumors with increased LOX family activity.
      In conclusion, our data support that LOX family activity is both a novel target
      to improve chemotherapy as well as a novel biomarker to predict gemcitabine
      benefit in PDAC. Beyond the PDAC, it is possible that targeting LOX family
      activity might improve efficacy of chemotherapies against different kinds of
      solid tumors. 

PMID- 27050074
TI  - Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung
      cancer.
AB  - New reliable biomarkers are needed to predict the response to immune checkpoint
      inhibitors against programmed death-1 (PD-1) and its ligand (PD-L1), because PD
      L1 expression on tumor cells has limited power for selecting patients who may
      benefit from such therapy. Here we investigated the significance of PD-L1 and PD
      L2 gene copy number gains using fluorescence in situ hybridization as well as PD
      L1 and PD-L2 expression in 654 patients with resected non-small-cell lung cancer.
      The prevalence of PD-L1 amplification and polysomy was 3.1% and 13.2%,
      respectively. The PD-L1 gene copy number status was in agreement with both the PD
      L2 and Janus kinase 2 gene copy number statuses. PD-L1 and PD-L2 expression was
      observed in 30.7% and 13.1%, respectively. Both PD-L1 copy number gains and
      expression were associated with smoking-related tumors. Tumor cells with PD-L1
      genomic gains exhibited significantly higher levels of PD-L1 expression than
      those without, but PD-L2 copy number gains were not related to PD-L2
      augmentation. PD-L1 gene amplification and polysomy were independently associated
      with PD-L1 expression, with high immune infiltrates and EGFR expression in a
      multivariate logistic regression model. Comparative analysis between primary
      tumors and synchronous regional lymph node metastases revealed that the PD-L1
      gene copy number alterations were highly consistent and reproducible compared
      with the PD-L1 expression. Both PD-L1 amplification and level of protein
      expression were predictors of poor survival using Cox univariate analyses.
      Therefore, we conclude that an increase in PD-L1 gene copy number can be a
      feasible alternative biomarker for predicting response to anti-PD-1/PD-L1
      therapy. 

PMID- 27050075
TI  - New insights into the prognostic value of Ki-67 labeling index in patients with
      triple-negative breast cancer.
AB  - The clinicopathological importance of the Ki-67 labeling index (LI) in breast
      cancer has been studied intensely; however, its prognostic significance in triple
      negative breast cancer (TNBC) is unclear. We aimed to determine the optimal Ki-67
      cut-off point to demonstrate its prognostic relevance for breast-cancer-specific
      survival (BCSS) in TNBC patients. A total of 571 female TNBC patients underwent
      diagnosis and surgery at our institution from January 2002 to June 2011.
      Clinicopathological information for all patients was available and categorized by
      Ki-67 LI and age at diagnosis. The cut-off values for Ki-67 LI and age were
      selected using the medians. A varying-coefficient Cox model was used to describe
      the effect of Ki-67 LI on BCSS outcomes changing with age after adjustment for
      disease characteristics. For survival analysis, the Kaplan-Meier method and the
      log-rank test were used. Cox proportional hazards models were applied to
      determine the association of Ki-67 LI and age with BCSS outcomes after adjustment
      for disease characteristics. Median age was 50 years, and median Ki-67 LI was 35%
      (range, 0 - 97.5%). There was no prognostic significance of stratification by Ki
      67 LI in all patients. When analyzing age at diagnosis as a continuous variable,
      the log-transformed HRKi67 > 35% vs. <= 35% for BCSS increased in an S-shaped
      curve with increasing age up to about 50 years-old and remained higher-risk for
      high Ki-67 LI. After adjusting for clinicopathological risk factors, low Ki-67 LI
      was a poor prognostic factor for BCSS (HR: 0.36, 95% CI: 0.14-0.96, P = 0.042) in
      patients of <= 50 years, but not in patients diagnosed at > 50 years (hazard
      ratio [HR]: 1.57, 95% CI: 0.76-3.22, P = 0.241). In conclusion, lower Ki-67 LI
      has poor prognosis relevance in TNBC patients diagnosed at <= 50 years-old.
      Further validation of the clinical significance of Ki-67 LI in TNBC is required. 

PMID- 27050076
TI  - Deregulation of IGF-binding proteins -2 and -5 contributes to the development of
      endocrine resistant breast cancer in vitro.
AB  - Tamoxifen (TAM) remains the adjuvant therapy of choice for pre-menopausal women
      with ERalpha-positive breast cancer. Resistance and recurrence remain, however, a
      major challenge with many women relapsing and subsequently dying. The insulin
      like growth factor (IGF) axis is involved in breast cancer pathogenesis and
      progression to endocrine resistant disease, but there is very little data on the
      expression and potential role of IGF-binding proteins (IGFBP) during acquisition
      of the resistant phenotype. The aim of this study was to determine the expression
      and functional role of IGFBP-2 and -5 in the development of TAM resistance (TamR)
      in vitro and to test retrospectively whether they were predictive of resistance
      in a tissue microarray of 77 women with primary breast cancers who relapsed
      on/after endocrine therapy and 193 who did not with long term follow up.
      Reciprocal expression of IGFBP-2 and IGFBP-5 was observed at both mRNA and
      protein level in TamR cells. IGFBP-2 expression was increased by 10-fold while
      IGFBP-5 was decreased by 100-fold, compared to TAM-sensitive control cells. shRNA
      mediated silencing of IGFBP-2 in TamR cells restored TAM sensitivity suggesting a
      causal role for this gene in TamR. While silencing of IGFBP-5 in control cells
      had no effect on TAM sensitivity, it significantly increased the migratory
      capacity of these cells. Quantitative image analysis of immunohistochemical data
      failed, however, to demonstrate an effect of IGFBP2 expression in endocrine
      relapsed patients. Likewise, IGFBP-2 and IGFBP-5 expression failed to show any
      significant associations with survival either in patients relapsing or those not
      relapsing on/after endocrine therapy. By contrast, in silico mining of a separate
      published dataset showed that in patients who received endocrine treatment, loss
      of expression of IGBP-5 was significantly associated with worse survival. Overall
      these data suggest that co-ordinated and reciprocal alteration in IGFBP-2 and -5
      expression may play a role in the acquisition of endocrine resistance. 

PMID- 27050077
TI  - Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system
      lymphoma.
AB  - Osteopontin (OPN) is the most upregulated gene in primary central nervous system
      lymphoma (PCNSL) compared to non-CNS diffuse large B cell lymphoma (DLBCL). We
      show here that OPN is a key mediator of intracerebral tumor growth, invasion, and
      dissemination in CNS lymphoma, and that these effects depend upon activation of
      NF-kappaB. We further show that activation of NF-kappaB by OPN occurs through a
      unique mechanism in which intracellular OPN (iOPN) causes transcriptional
      downregulation of the NF-kappaB inhibitors, A20/TNFAIP3 and ABIN1/TNIP1, and
      secretory OPN (sOPN) promotes receptor-mediated activation of NF-kappaB. We also
      identify NF-kappaB-mediated induction of matrix metalloproteinase-8 (MMP-8) as a
      specific feature of OPN-mediated tissue invasion. These results implicate OPN as
      a candidate for development of targeted therapy for patients with PCNSL. 

PMID- 27050079
TI  - IL-27 levels are low in enthesitis-related arthritis category of juvenile
      idiopathic arthritis.
AB  - OBJECTIVES: Enthesitis-related arthritis (ERA) is associated with the increase in
      frequency of Th17 cells and synovial fluid IL-17 levels. Recently, IL-15 and IL
      18 has been shown to augment and IL-27 to suppress IL-17 production in autoimmune
      disease, and thus we studied these cytokines in ERA patients. METHODS: Serum
      samples were collected from 55 patients with ERA, 21 with other categories of JIA
      and 21 healthy controls. 19 paired synovial fluid samples were also collected
      from ERA patients. IL-17, IL-23, IL-15, IL-18 and IL-27 levels were measured by
      ELISA and Th17 frequency was assessed by flow cytometry. IL-23 levels and Th17
      frequency was done in subsets of patients. RESULTS: The median disease duration
      was 36 months in ERA and 24 months in other JIA subjects. No difference was found
      in serum levels of IL-17, IL-23, IL-15 and IL-18 between ERA and controls whereas
      the median IL-27 serum levels were decreased in ERA (107.94 pg/ml (<64-444.40
      pg/ml)) as compared to healthy controls (267.28 pg/ml (80.90-492.15 pg/ml);
      p=0.008). In ERA, synovial fluid levels of IL-17, IL-15 and IL-18 were
      significantly increased but IL-27 levels were significantly decreased as compared
      to serum levels. Synovial IL-27 levels correlated negatively with Th17 cell
      frequency (n=11; r=-0.651, p=0.03). CONCLUSIONS: IL-17 and its supporting
      cytokines IL-15 and IL-18 are increased whereas its regulatory cytokine IL-27 is
      decreased in synovial compartment, thus the balance is tilted in favour of IL-17
      production. Strategies to increase IL-27 may have therapeutic potential in
      controlling inflammation at local site.

PMID- 27050078
TI  - Mutation profiling in chinese patients with metastatic colorectal cancer and its
      correlation with clinicopathological features and anti-EGFR treatment response.
AB  - An increasing number of studies reveal the significance of genetic markers in
      guiding target treatment and refining prognosis. This retrospective observational
      study aims to assess the mutation profile of metastatic colorectal cancer (mCRC)
      in Chinese population with the help of MassARRAY(r) technique platform and
      OncoCartaTM Panel.322 Chinese patients with mCRC who received clinical molecular
      testing as part of their standard care were investigated. 80 patients received
      cetuximab palliative treatment. 238 common hot-spot mutations of 19 cancer
      related genes in the OncoCartaTM Panel were tested.44 mutations in 11 genes were
      detected in 156 cases (48.4%). At least one mutation was identified in 38.5%
      (124/322) of all tested cases, two concomitant mutations in 9.0% (29/322) and
      three mutations in 3 cases (<1%). KRAS was the most frequently mutated gene
      (34.8%), followed by PIK3CA (9.6%), NRAS (4.3%), BRAF (3.4%), EGFR (2.5%) and
      HRAS (1.2%). Less frequent mutations were detected in PDGFRA, RET, AKT1, FGFR1,
      and ERBB2. Co-mutation of RAS family subtypes was observed in 5 patients, and
      KRAS and BRAF concurrent mutation in 1 patient. KRAS, NRAS, BRAF and PIK3CA
      mutations had association with some clinicopathological features statistically.
      Patients identified as wild-type in all 19 genes had better objective response
      rate when treated with cetuximab.The clinical molecular testing with OncoCartaTM
      Panel supplemented the limited data of mCRC in Chinese population, and offered a
      clearer landscape of multiple gene mutational profile in not only clinically
      prognostic KRAS, NRAS, BRAF and PIK3CA genes, but also less frequent mutated
      genes. Knowledge of these multiple gene mutation patterns may give clues in
      exploring interesting accompanying co-occurrence relationship or mutually
      exclusive relationship between mutated genes, as well as in predicting benefit of
      all-wild-type patients from anti-EGFR treatment. 

PMID- 27050080
TI  - Research highlights: laboratory studies of the formation and transformation of
      atmospheric organic aerosols.
AB  - Atmospheric particles are emitted from a variety of anthropogenic and natural
      precursors and have direct impacts on climate, by scattering solar irradiation
      and nucleating clouds, and on health, by causing oxidative stress in the lungs
      when inhaled. They may also form from gaseous precursors, creating complex
      mixtures of organic and inorganic material. The chemical composition and the
      physical properties of aerosols will evolve during their one-week lifetime which
      will consequently change their impact on climate and health. The heterogeneity of
      aerosols is difficult to model and thus atmospheric aerosol research strives to
      characterize the mechanisms involved in nucleating and transforming particles in
      the atmosphere. Recent advances in four laboratory studies of aerosol formation
      and aging are highlighted here. 

PMID- 27050081
TI  - Episode-Based Evolution Pattern Analysis of Haze Pollution: Method Development
      and Results from Beijing, China.
AB  - Haze episodes occurred in Beijing repeatedly in 2013, resulting in 189 polluted
      days. These episodes differed in terms of sources, formation processes, and
      chemical composition and thus required different control policies. Therefore, an
      overview of the similarities and differences among these episodes is needed. For
      this purpose, we conducted one-year online observations and developed a program
      that can simultaneously divide haze episodes and identify their shapes. A total
      of 73 episodes were identified, and their shapes were linked with synoptic
      conditions. Pure-haze events dominated in wintertime, whereas mixed haze-dust
      (PM2.5/PM10 < 60%) and mixed haze-fog (Aerosol Water/PM2.5 ~ 0.3) events
      dominated in spring and summer-autumn, respectively. For all types, increase of
      ratio of PM2.5 in PM10 was typically achieved before PM2.5 reached ~150 MUg/m(3).
      In all PM2.5 species observed, organic matter (OM) was always the most abundant
      component (18-60%), but it was rarely the driving factor: its relative
      contribution usually decreased as the pollution level increased. The only OM
      driven episode observed was associated with intensive biomass-burning activities.
      In comparison, haze evolution generally coincided with increasing sulfur and
      nitrogen oxidation ratios (SOR and NOR), indicating the enhanced production of
      secondary inorganic species. Applicability of these conclusions required further
      tests with simultaneously multisite observations. 

PMID- 27050082
TI  - Is customized vestibular rehabilitation effective in patients with multiple
      sclerosis? A randomized controlled trial.
AB  - BACKGROUND: Balance disorders are among the most common problems encountered by
      patients diagnosed with multiple sclerosis (MS). AIM: The purpose of this
      randomized, controlled trial was to investigate the effects of customized
      vestibular rehabilitation (VR) on balance, functional capacity, quality of life,
      and depression in patients with MS. DESIGN: This study was designed as a
      prospective, randomized, controlled trial. SETTING: The study was carried out in
      a single tertiary referral center. POPULATION: Forty consecutive patients
      referred with a diagnosis of MS were randomized into two groups: an exercise
      group (N.=20) and a control group (N.=20). METHODS: The experimental group
      underwent customized VR and the wait-listed control group received the usual
      medical care. All of the patients were assessed with objective balance tests
      (Romberg Test, Tandem Romberg Test, Foam Romberg Test, Static Posturography, Six
      Meter Walk Test, Five Times Sit-to-Stand Test, Berg Balance Scale, Timed Up and
      Go Test, Functional Gait Assessment, and Dynamic Gait Index), subjective balance
      parameters (Activities-Specific Balance Confidence Scale and Dizziness Handicap
      Inventory), and functional capacity (Six-Minute Walking Test), quality of life
      (Multiple Sclerosis Quality of Life-54), and depression (Beck Depression
      Inventory) scales. RESULTS: At the end of the trial, the exercise group exhibited
      significant changes in most of the evaluated parameters compared to the control
      group [except the Tandem Romberg with eyes closed and the Foam Romberg, standing
      with eyes open (P<0.05). No significant differences were observed in any of the
      parameters in the control group (P>0.05). The intergroup comparisons of
      differences indicated significant recoveries in favor of the exercise group in
      all of the evaluated parameters (P<0.05). CONCLUSIONS: This study confirms the
      effects of customized VR programs on balance, quality of life, and functional
      capacity in patients with MS. CLINICAL REHABILITATION IMPACT: Customized VR is an
      effective method for treating balance disorders in patients with MS.

PMID- 27050083
TI  - Rehabilitation pathways and functional independence one year after severe
      traumatic brain injury.
AB  - BACKGROUND: After severe traumatic brain injury (TBI) it is recommended that
      patients in need of rehabilitation be transferred directly from acute care to
      specialized rehabilitation. However, recent European cohort studies found a
      variety of care pathways and delays in admission to rehabilitation after severe
      TBI. AIM: To study the pathways within rehabilitation services in a Norwegian
      national cohort with severe TBI and the association to functional independence 12
      months post-injury. DESIGN: Observational prospective multicenter study. SETTING:
      Regional trauma centers. POPULATION: A total of 163 adults, age 16-85 years, with
      severe TBI. METHODS: The main variables were transfer between acute care and
      rehabilitation, type of rehabilitation services and functional independence.
      RESULTS: 75% of the patients had specialized TBI rehabilitation, 11% non
      specialized and 14% no in-patient rehabilitation. In total, 48% were transferred
      directly to specialized rehabilitation from acute units in regional trauma
      centers. There were no differences in injury severity between patients
      transferred directly and non-directly, but the direct-transfer patients were
      younger. At 12 months post-injury, 71% were functionally independent and 90%
      lived in their home. Younger age, fewer days of ventilation and shorter post
      traumatic amnesia were associated with independence. Among patients treated with
      specialized rehabilitation, direct transfer to rehabilitation was associated with
      functional independence (OR=4.3, P<0.01). CONCLUSIONS: A direct clinical pathway
      including specialized rehabilitation in dedicated units was associated with
      functional independence. CLINICAL REHABILITATION IMPACT: Direct pathways from
      acute care to sub-acute specialized rehabilitation might prove beneficial to
      functional status.

PMID- 27050085
TI  - Corrigendum.

PMID- 27050084
TI  - Comparison between two functional mobility scales for Parkinson's disease
      directly applied to physical therapy practice: cross-cultural adaptation and
      measurement properties.
AB  - BACKGROUND: The Modified Parkinson Activity Scale (PASm) and Lindop Parkinson's
      Disease Mobility Assessment (LPA) scales were developed to assess the functional
      mobility in patients with Parkinson's disease (PD) being directly applied to
      physical therapy practice. AIM: To translate and perform the cross-cultural
      adaptation of PASm and LPA scales to Portuguese-Brazil, and to analyze some
      psychometric properties. DESIGN: Cross-cultural validation study. SETTING:
      Clinical environment. POPULATION: Thirty-two Brazilian subjects with Parkinson's
      disease. METHODS: The study consisted of two stages: 1) cross-cultural adaptation
      process; 2) evaluation of psychometric properties. RESULTS: Considering the total
      score, the interrater and test-retest reliabilities showed a coefficient of intra
      class correlation that ranged between 0.97 and 0.98. Both scales showed excellent
      internal consistency (alpha=0.83 and 0.94). Positive correlations were obtained
      between the Brazilian versions of the LPA and PASm and PAS (rho=0.63 and 0.92).
      The concurrent validity between scales and part III of UPDRS, established a
      moderate negative correlation, (rho=-0.54 and -0.65). The one way ANOVA showed
      that LPA-Brazil discriminates the individual with PD between all stages according
      HY, and the PASm- Brazil between mild and severe stages, and moderate and severe.
      The MDC of scales ranging from 1 to 2 points. There was Ceiling effect only for
      the LPA-Brazil. CONCLUSIONS: Brazilian versions of PASm and LPA are valid and
      reliable instruments to assess the functional mobility in patients with PD, being
      directly applied to physical therapy clinical practice. CLINICAL REHABILITATION
      IMPACT: The major goal of physical therapy in PD is to maintain functional
      mobility and independence of the patient. The results of study are relevant and
      could improve the physical therapy practice in Brazil, since it provides the
      Brazilian version of two mobility scales (one of them recommended by the European
      Guidelines for Physical Therapy Practice in patients with Parkinson disease).

PMID- 27050086
TI  - One-pot, regiospecific assembly of (E)-benzamidines from delta- and gamma-amino
      acids via an intramolecular aminoquinazolinone rearrangement.
AB  - The efficient generation of novel, N-linked benzamidines resulting from a
      regiospecific rearrangement of quinazolinones is described. This methodology
      study explored reaction parameters including the effect of changing solvent and
      temperature, as well as varying electronic substituents on the structural core.
      The transformation was extensively optimized in terms of reaction conditions and
      scope, resulting in a protocol that consistently affords diversely functionalized
      amidines in high yield. The process permits regional structural derivatization
      that was previously inaccessible, and the multistep process was also reduced to a
      telescoped, five-step sequence that efficiently affords pharmacologically unique
      (E)-benzamidoamidines from N-BOC protected gamma- and delta-amino acids. 

PMID- 27050087
TI  - Planning for subacute care: predicting demand using acute activity data.
AB  - Objective The aim of the present study was to develop a robust model that uses
      the concept of 'rehabilitation-sensitive' Diagnosis Related Groups (DRGs) in
      predicting demand for rehabilitation and geriatric evaluation and management
      (GEM) care following acute in-patient episodes provided in Australian hospitals.
      Methods The model was developed using statistical analyses of national datasets,
      informed by a panel of expert clinicians and jurisdictional advice. Logistic
      regression analysis was undertaken using acute in-patient data, published
      national hospital statistics and data from the Australasian Rehabilitation
      Outcomes Centre. Results The predictive model comprises tables of probabilities
      that patients will require rehabilitation or GEM care after an acute episode,
      with columns defined by age group and rows defined by grouped Australian Refined
      (AR)-DRGs. Conclusions The existing concept of rehabilitation-sensitive DRGs was
      revised and extended. When applied to national data, the model provided a
      conservative estimate of 83% of the activity actually provided. An example
      demonstrates the application of the model for service planning. What is known
      about the topic? Health service planning is core business for jurisdictions and
      local areas. With populations ageing and an acknowledgement of the underservicing
      of subacute care, it is timely to find improved methods of estimating demand for
      this type of care. Traditionally, age-sex standardised utilisation rates for
      individual DRGs have been applied to Australian Bureau of Statistics (ABS)
      population projections to predict the future need for subacute services. Improved
      predictions became possible when some AR-DRGs were designated 'rehabilitation
      sensitive'. This improved methodology has been used in several Australian
      jurisdictions. What does this paper add? This paper presents a new tool, or
      model, to predict demand for rehabilitation and GEM services based on in-patient
      acute activity. In this model, the methodology based on rehabilitation-sensitive
      AR-DRGs has been extended by updating them to AR-DRG Version 7.0, quantifying the
      level of 'sensitivity' and incorporating the patient's age to improve the
      prediction of demand for subacute services. What are the implications for
      practitioners? The predictive model takes the form of tables of probabilities
      that patients will require rehabilitation or GEM care after an acute episode and
      can be applied to acute in-patient administrative datasets in any Australian
      jurisdiction or local area. The use of patient-level characteristics will enable
      service planners to improve their forecasting of demand for these services.
      Clinicians and jurisdictional representatives consulted during the project
      regarded the model favourably and believed that it was an improvement on
      currently available methods.

PMID- 27050088
TI  - Catalytic stereoselective cascade reactions of quinols with trifluoromethyl
      ketones: direct access to CF3-containing 1,3-dioxolanes.
AB  - A general and efficient synthesis of CF3-containing 1,3-dioxolanes using Et3N
      catalyzed ketalization/oxa-Michael cascade of quinols with trifluoromethyl
      ketones is described. The reaction works efficiently under mild reaction
      conditions and produces the desired products in 68%-95% yields with acceptable
      diastereoselectivities. In addition, the reaction proceeds smoothly to give the
      desired product 3a in 92% yield and with high ee (80%) in the presence of a
      chiral catalyst (DHQ)2PHAL. 

PMID- 27050089
TI  - Vancomycin-sensitive bacteria trigger development of colitis-associated colon
      cancer by attracting neutrophils.
AB  - Inflammatory bowel disease confers an increased risk of developing colitis
      associated colon cancer (CAC). During the active colitis or developing tumor
      stage, commensal bacteria show dynamic translocation. However, whether alteration
      of the bacterial composition in the gut causes CAC is still unclear. To clarify
      the effect of commensal bacteria on CAC development, we employed an azoxymethane
      (AOM) and dextran sodium sulfate (DSS)-induced murine CAC model treated with or
      without antibiotics. In addition, we analyzed the effects of antibiotics on
      infiltration of myeloid cells, colonic inflammatory responses, and colorectal
      cancer formation. We found that vancomycin treatment dramatically suppressed
      tumor development. In addition, AOM/DSS treatment greatly induced the
      infiltration of Gr-1(high)/CD11b(high) neutrophils to the colon, which led to the
      production of tumor necrosis factor alpha and inducible nitric oxide synthase.
      Vancomycin treatment suppressed the infiltration of neutrophils induced by
      AOM/DSS. Moreover, vancomycin treatment greatly reduced the colon injury and DNA
      damage caused by AOM/DSS-induced NO radicals. Our results indicate that
      vancomycin-sensitive bacteria induced colon inflammation and DNA damage by
      attracting neutrophils into damaged colon tissue, thus promoting tumor formation.

PMID- 27050090
TI  - Brown seaweeds protect against azoxymethane-induced hepatic repercussions through
      up-regulation of peroxisome proliferator-activated receptor gamma and attenuation
      of oxidative stress.
AB  - CONTEXT: Seaweeds of the genera Turbinaria and Padina have long been used as food
      and in traditional medicine for treating several diseases. OBJECTIVE: The current
      study determines the protective efficacy of the brown seaweeds Turbinaria ornata
      (Turner) J. Agardh (Sargassaceae) and Padina pavonia (Linnaeus) J.V. Lamouroux
      (Dictyotaceae) against liver injury induced by azoxymethane (AOM). MATERIALS AND
      METHODS: Male Swiss mice received 10 mg/kg AOM once a week for two consecutive
      weeks and then 100 mg/kg daily dose of either T. ornata or P. pavonia ethanolic
      extract. Thirteen weeks after the first AOM administration and 24 h after the
      last treatment, overnight fasted mice were sacrificed and samples collected.
      RESULTS: Compared with the AOM group, both T. ornata and P. pavonia significantly
      decreased the activity of aminotransferases and the concentration of bilirubin
      while increased albumin levels in the serum. The antioxidative effect of both
      extracts was observed from the increased activity of superoxide dismutase and
      glutathione peroxidase activities in the liver, both of which were decreased by
      AOM. Moreover, the levels of malondialdehyde and nitric oxide were reduced, and
      histological findings also confirmed the antihepatotoxic activity. In addition,
      treatment with T. ornata and P. pavonia significantly increased PPARgamma and
      decreased NF-kappaB expression in the liver of AOM-administered mice. DISCUSSION
      AND CONCLUSION: Our findings indicate that the protective function of T. ornata
      and P. pavonia on AOM-induced liver injury may be possibly exerted by multiple
      pathways including abolishment of inflammation and oxidative damage, and
      activation of PPARgamma.

PMID- 27050091
TI  - Remission for Loss of Odontogenic Potential in a New Micromilieu In Vitro.
AB  - During embryonic organogenesis, the odontogenic potential resides in dental
      mesenchyme from the bud stage until birth. Mouse dental mesenchymal cells (mDMCs)
      isolated from the inductive dental mesenchyme of developing molars are frequently
      used in the context of tooth development and regeneration. We wondered if and how
      the odontogenic potential could be retained when mDMCs were cultured in vitro. In
      the present study, we undertook to test the odontogenic potential of cultured
      mDMCs and attempted to maintain the potential during culturing. We found that
      cultured mDMCs could retain the odontogenic potential for 24 h with a ratio of
      60% for tooth formation, but mDMCs were incapable of supporting tooth formation
      after more than 24 h in culture. This loss of odontogenic potential was
      accompanied by widespread transcriptomic alteration and, specifically, the
      downregulation of some dental mesenchyme-specific genes, such as Pax9, Msx1, and
      Pdgfralpha. To prolong the odontogenic potential of mDMCs in vitro, we then
      cultured mDMCs in a serum-free medium with Knockout Serum Replacement (KSR) and
      growth factors (fibroblastic growth factor 2 and epidermal growth factor). In
      this new micromilieu, mDMCs could maintain the odontogenic potential for 48 h
      with tooth formation ratio of 50%. Moreover, mDMCs cultured in KSR-supplemented
      medium gave rise to tooth-like structures when recombined with non-dental second
      arch epithelium. Among the supplements, KSR is essential for the survival and
      adhesion of mDMCs, and both Egf and Fgf2 induced the expression of certain dental
      mesenchyme-related genes. Taken together, our results demonstrated that the
      transcriptomic changes responded to the alteration of odontogenic potential in
      cultured mDMCs and a new micromilieu partly retained this potential in vitro,
      providing insight into the long-term maintenance of odontogenic potential in
      mDMCs. 

PMID- 27050093
TI  - Electrical Stimulation of Coleopteran Muscle for Initiating Flight.
AB  - Some researchers have long been interested in reconstructing natural insects into
      steerable robots or vehicles. However, until recently, these so-called cyborg
      insects, biobots, or living machines existed only in science fiction. Owing to
      recent advances in nano/micro manufacturing, data processing, and anatomical and
      physiological biology, we can now stimulate living insects to induce user-desired
      motor actions and behaviors. To improve the practicality and applicability of
      airborne cyborg insects, a reliable and controllable flight initiation protocol
      is required. This study demonstrates an electrical stimulation protocol that
      initiates flight in a beetle (Mecynorrhina torquata, Coleoptera). A reliable
      stimulation protocol was determined by analyzing a pair of dorsal longitudinal
      muscles (DLMs), flight muscles that oscillate the wings. DLM stimulation has
      achieved with a high success rate (> 90%), rapid response time (< 1.0 s), and
      small variation (< 0.33 s; indicating little habituation). Notably, the
      stimulation of DLMs caused no crucial damage to the free flight ability. In
      contrast, stimulation of optic lobes, which was earlier demonstrated as a
      successful flight initiation protocol, destabilized the beetle in flight. Thus,
      DLM stimulation is a promising secure protocol for inducing flight in cyborg
      insects or biobots. 

PMID- 27050094
TI  - Analysis of internal and external validity criteria for a computerized visual
      search task: A pilot study.
AB  - Inhibition is one of the main executive functions, because of its fundamental
      role in cognitive and social development. Given the importance of reliable and
      computerized measurements to assessment inhibitory performance, this research
      intends to analyze the internal and external criteria of validity of a
      computerized conjunction search task, to evaluate the role of perceptual
      inhibition. A sample of 41 children (21 females and 20 males), aged between 6 and
      11 years old (M = 8.49, SD = 1.47), intentionally selected from a private
      management school of Mar del Plata (Argentina), middle socio-economic level were
      assessed. The Conjunction Search Task from the TAC Battery, Coding and Symbol
      Search tasks from Wechsler Intelligence Scale for Children were used. Overall,
      results allow us to confirm that the perceptual inhibition task form TAC presents
      solid rates of internal and external validity that make a valid measurement
      instrument of this process.

PMID- 27050092
TI  - Effect of Vitamin D on Peripheral Blood Mononuclear Cells from Patients with
      Psoriasis Vulgaris and Psoriatic Arthritis.
AB  - BACKGROUND: Psoriasis, a chronic skin disease with or without joint inflammation,
      has increased circulating proinflammatory cytokine levels. Vitamin D is involved
      in calcium homeostasis, bone formation, osteoclastogenesis and osteoclast
      activity, as well as regulation of immune response. We aimed to study osteoclast
      differentiation and cytokine secretion of peripheral blood mononuclear cells
      (PBMCs) from patients with psoriasis vulgaris and psoriatic arthritis, in
      response to 1,25(OH)2D3. METHODS: Serum levels of bone turnover markers were
      measured by ELISA in patients with psoriasis vulgaris and psoriatic arthritis,
      and healthy controls. PBMCs were isolated and cultured with or without RANKL/M
      CSF and 1,25(OH)2D3. Osteoclast differentiation and cytokine secretion were
      assessed. RESULTS: Psoriatic arthritis patients had lower osteocalcin, as well as
      higher C-telopeptide of type I collagen and cathepsin K serum levels compared
      with psoriasis vulgaris patients and controls. RANKL/M-CSF-stimulated PBMCs from
      psoriatic arthritis patients produced higher proinflammatory cytokine levels and
      had a differential secretion profile in response to 1,25(OH)2D3, compared with
      psoriasis vulgaris and control PBMCs. CONCLUSIONS: Our data confirmed altered
      bone turnover in psoriatic arthritis patients, and demonstrated increased
      osteoclastogenic potential and proinflammatory cytokine secretion capacity of
      these PBMCs compared with psoriasis vulgaris and controls. 1,25(OH)2D3 abrogated
      these effects.

PMID- 27050095
TI  - Trends in Respiratory Syncytial Virus and Bronchiolitis Hospitalization Rates in
      High-Risk Infants in a United States Nationally Representative Database, 1997
      2012.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) causes significant pediatric
      morbidity and is the most common cause of bronchiolitis. Bronchiolitis
      hospitalizations declined among US infants from 2000-2009; however, rates in
      infants at high risk for RSV have not been described. This study examined RSV and
      unspecified bronchiolitis (UB) hospitalization rates from 1997-2012 among US high
      risk infants. METHODS: The Kids' Inpatient Database (KID) infant annual RSV (ICD
      9 079.6, 466.11, 480.1) and UB (ICD-9 466.19, 466.1) hospitalization rates were
      estimated using weighted counts. Denominators were based on birth
      hospitalizations with conditions associated with high-risk for RSV: chronic
      perinatal respiratory disease (chronic lung disease [CLD]); congenital airway
      anomalies (CAA); congenital heart disease (CHD); Down syndrome (DS); and other
      genetic, metabolic, musculoskeletal, and immunodeficiency conditions. Preterm
      infants could not be identified. Hospitalizations were characterized by
      mechanical ventilation, inpatient mortality, length of stay, and total cost
      (2015$). Poisson and linear regression were used to test statistical significance
      of trends. RESULTS: RSV and UB hospitalization rates were substantially elevated
      for infants with higher-risk CHD, CLD, CAA and DS without CHD compared with all
      infants. RSV rates declined by 47.0% in CLD and 49.7% in higher-risk CHD infants;
      no other declines in high-risk groups were observed. UB rates increased in all
      high-risk groups except for a 22.5% decrease among higher-risk CHD. Among high
      risk infants, mechanical ventilation increased through 2012 to 20.4% and 13.5% of
      RSV and UB hospitalizations; geometric mean cost increased to $31,742 and
      $25,962, respectively, and RSV mortality declined to 0.9%. CONCLUSIONS: Among
      high-risk infants between 1997 and 2012, RSV hospitalization rates declined among
      CLD and higher-risk CHD infants, coincident with widespread RSV immunoprophylaxis
      use in these populations. UB hospitalization rates increased in all high-risk
      groups except higher-risk CHD, suggesting improvement in the health status of
      higher-risk CHD infants, potentially due to enhanced surgical interventions.
      Mechanical ventilation use and RSV and UB hospitalization costs increased while
      RSV mortality declined.

PMID- 27050096
TI  - Electrophysiological and Anatomical Correlates of Spinal Cord Optical Coherence
      Tomography.
AB  - Despite the continuous improvement in medical imaging technology, visualizing the
      spinal cord poses severe problems due to structural or incidental causes, such as
      small access space and motion artifacts. In addition, positional guidance on the
      spinal cord is not commonly available during surgery, with the exception of
      neuronavigation techniques based on static pre-surgical data and of radiation
      based methods, such as fluoroscopy. A fast, bedside, intraoperative real-time
      imaging, particularly necessary during the positioning of endoscopic probes or
      tools, is an unsolved issue. The objective of our work, performed on experimental
      rats, is to demonstrate potential intraoperative spinal cord imaging and probe
      guidance by optical coherence tomography (OCT). Concurrently, we aimed to
      demonstrate that the electromagnetic OCT irradiation exerted no particular effect
      at the neuronal and synaptic levels. OCT is a user-friendly, low-cost and
      endoscopy-compatible photonics-based imaging technique. In particular, by using a
      Fourier-domain OCT imager, operating at 850 nm wavelength and scanning
      transversally with respect to the spinal cord, we have been able to: 1)
      accurately image tissue structures in an animal model (muscle, spine bone,
      cerebro-spinal fluid, dura mater and spinal cord), and 2) identify the position
      of a recording microelectrode approaching and inserting into the cord tissue 3)
      check that the infrared radiation has no actual effect on the
      electrophysiological activity of spinal neurons. The technique, potentially
      extendable to full three-dimensional image reconstruction, shows prospective
      further application not only in endoscopic intraoperative analyses and for probe
      insertion guidance, but also in emergency and adverse situations (e.g. after
      trauma) for damage recognition, diagnosis and fast image-guided intervention. 

PMID- 27050097
TI  - Correction: A Health Threat to Bystanders Living in the Homes of Smokers: How
      Smoke Toxins Deposited on Surfaces Can Cause Insulin Resistance.

PMID- 27050098
TI  - High oblique sagittal split osteotomy of the mandible: assessment of the
      positions of the mandibular condyles after orthognathic surgery based on cone
      beam tomography.
AB  - High oblique sagittal split osteotomy is an orthognathic technique to move the
      mandible. Our aim was to evaluate changes in the position of the condyle in the
      glenoid fossa and its angulation before and after high oblique sagittal split
      osteotomy (HSSO). Fifty patients (32 women and 18 men, mean age 26.3 (SD 7.4)
      years) had cone-beam computed tomographyic (CT) scans before operation,
      immediately postoperatively, and before removal of the osteosynthesis nine months
      postoperatively. The images were analysed to look for changes in the sagittal,
      coronal, and axial positions of the condyles. Twenty-four patients with class II
      malocclusion had a mean (SD) mandibular advancement of 6.51 (2.41) mm, and 26
      patients with class III malocclusion had a mean (SD) mandibular setback of 4.16
      (2.77) mm. The joint space increased significantly (p<0.05) relative to baseline
      immediately postoperatively, but there was no significant increase at the nine
      month follow-up. The changes in position in the sagittal, coronal, and axial
      planes were comparable. Despite there being a short proximal joint-bearing
      segment, the results indicate that this technique allows free-hand condylar
      positioning into the fossa safely without any clinically relevant dislocations. 

PMID- 27050099
TI  - N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate
      Epithelial Cells.
AB  - MYCN amplification and overexpression are common in neuroendocrine prostate
      cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate
      tumorigenesis and the cellular origin of NEPC have not been established. We
      define N-Myc and activated AKT1 as oncogenic components sufficient to transform
      human prostate epithelial cells to prostate adenocarcinoma and NEPC with
      phenotypic and molecular features of aggressive, late-stage human disease. We
      directly show that prostate adenocarcinoma and NEPC can arise from a common
      epithelial clone. Further, N-Myc is required for tumor maintenance, and
      destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden.
      Our findings establish N-Myc as a driver of NEPC and a target for therapeutic
      intervention. 

PMID- 27050101
TI  - The Role of Personalised Choice in Decision Support: A Randomized Controlled
      Trial of an Online Decision Aid for Prostate Cancer Screening.
AB  - IMPORTANCE: Decision support tools can assist people to apply population-based
      evidence on benefits and harms to individual health decisions. A key question is
      whether "personalising" choice within decisions aids leads to better decision
      quality. OBJECTIVE: To assess the effect of personalising the content of a
      decision aid for prostate cancer screening using the Prostate Specific Antigen
      (PSA) test. DESIGN: Randomized controlled trial. SETTING: Australia.
      PARTICIPANTS: 1,970 men aged 40-69 years were approached to participate in the
      trial. INTERVENTION: 1,447 men were randomly allocated to either a standard
      decision aid with a fixed set of five attributes or a personalised decision aid
      with choice over the inclusion of up to 10 attributes. OUTCOME MEASURES: To
      determine whether there was a difference between the two groups in terms of: 1)
      the emergent opinion (generated by the decision aid) to have a PSA test or not;
      2) self-rated decision quality after completing the online decision aid; 3) their
      intention to undergo screening in the next 12 months. We also wanted to determine
      whether men in the personalised choice group made use of the extra decision
      attributes. RESULTS: 5% of men in the fixed attribute group scored 'Have a PSA
      test' as the opinion generated by the aid, as compared to 62% of men in the
      personalised choice group (chi2 = 569.38, 2df, p< 0001). Those men who used the
      personalised decision aid had slightly higher decision quality (t = 2.157, df =
      1444, p = 0.031). The men in the personalised choice group made extensive use of
      the additional decision attributes. There was no difference between the two
      groups in terms of their stated intention to undergo screening in the next 12
      months. CONCLUSIONS: Together, these findings suggest that personalised decision
      support systems could be an important development in shared decision-making and
      patient-centered care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry (ANZCTR) ACTRN12612000723886.

PMID- 27050100
TI  - Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.
AB  - The childhood brain tumor, medulloblastoma, includes four subtypes with very
      different prognoses. Here, we show that paracrine signals driven by mutant beta
      catenin in WNT-medulloblastoma, an essentially curable form of the disease,
      induce an aberrant fenestrated vasculature that permits the accumulation of high
      levels of intra-tumoral chemotherapy and a robust therapeutic response. In
      contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact
      blood brain barrier, rendering this tumor impermeable and resistant to
      chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be
      manipulated in vivo, altering chemotherapy permeability and clinical response.
      Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in
      part the disparate prognoses among medulloblastoma subtypes and suggesting an
      approach to enhance the chemoresponsiveness of other brain tumors.

PMID- 27050102
TI  - Israel: Health System Review.
AB  - Israel is a small country, with just over 8 million citizens and a modern market
      based economy with a comparable level of gross domestic product per capita to the
      average in the European Union. It has had universal health coverage since the
      introduction of a progressively financed statutory health insurance system in
      1995. All citizens can choose from among four competing, non-profit-making health
      plans, which are charged with providing a broad package of benefits stipulated by
      the government. Overall, the Israeli health care system is quite efficient.
      Health status levels are comparable to those of other developed countries, even
      though Israel spends a relatively low proportion of its gross domestic product on
      health care (less than 8%) and nearly 40% of that is privately financed. Factors
      contributing to system efficiency include regulated competition among the health
      plans, tight regulatory controls on the supply of hospital beds, accessible and
      professional primary care and a well-developed system of electronic health
      records. Israeli health care has also demonstrated a remarkable capacity to
      innovate, improve, establish goals, be tenacious and prioritize. Israel is in the
      midst of numerous health reform efforts. The health insurance benefits package
      has been extended to include mental health care and dental care for children. A
      multipronged effort is underway to reduce health inequalities. National projects
      have been launched to measure and improve the quality of hospital care and reduce
      surgical waiting times, along with greater public dissemination of comparative
      performance data. Major steps are also being taken to address projected shortages
      of physicians and nurses. One of the major challenges currently facing Israeli
      health care is the growing reliance on private financing, with potentially
      deleterious effects for equity and efficiency. Efforts are currently underway to
      expand public financing, improve the efficiency of the public system and
      constrain the growth of the private sector. 

PMID- 27050103
TI  - Correction: Routine Pediatric Enterovirus 71 Vaccination in China: a Cost
      Effectiveness Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1001975.]. 

PMID- 27050104
TI  - The pathogenesis of congenital radial head dislocation/subluxation.
AB  - The pathogenesis of congenital radial head dislocation/subluxation is unknown and
      has not been previously investigated. In this review, we explore the pathogenesis
      and define five different primary insults: collagen abnormalities, abnormal
      endochondral ossification of the developing growth plate, abnormalities of
      forearm ossification outside the growth plate, disproportionate growth of the
      radius and ulna, and altered HOX D expression/activity. Finally, the clinical
      relevance of our review is discussed. 

PMID- 27050105
TI  - Brain in situ hybridization maps as a source for reverse-engineering
      transcriptional regulatory networks: Alzheimer's disease insights.
AB  - Microarray data have been a valuable resource for identifying transcriptional
      regulatory relationships among genes. As an example, brain region-specific
      transcriptional regulatory events have the potential of providing etiological
      insights into Alzheimer Disease (AD). However, there is often a paucity of
      suitable brain-region specific expression data obtained via microarrays or other
      high throughput means. The Allen Brain Atlas in situ hybridization (ISH) data
      sets (Jones et al., 2009) represent a potentially valuable alternative source of
      high-throughput brain region-specific gene expression data for such purposes. In
      this study, Allen Brain Atlas mouse ISH data in the hippocampal fields were
      extracted, focusing on 508 genes relevant to neurodegeneration. Transcriptional
      regulatory networks were learned using three high-performing network inference
      algorithms. Only 17% of regulatory edges from a network reverse-engineered based
      on brain region-specific ISH data were also found in a network constructed upon
      gene expression correlations in mouse whole brain microarrays, thus showing the
      specificity of gene expression within brain sub-regions. Furthermore, the ISH
      data-based networks were used to identify instructive transcriptional regulatory
      relationships. Ncor2, Sp3 and Usf2 form a unique three-party regulatory motif,
      potentially affecting memory formation pathways. Nfe2l1, Egr1 and Usf2 emerge
      among regulators of genes involved in AD (e.g. Dhcr24, Aplp2, Tia1, Pdrx1, Vdac1,
      and Syn2). Further, Nfe2l1, Egr1 and Usf2 are sensitive to dietary factors and
      could be among links between dietary influences and genes in the AD etiology.
      Thus, this approach of harnessing brain region-specific ISH data represents a
      rare opportunity for gleaning unique etiological insights for diseases such as
      AD. 

PMID- 27050106
TI  - Transclival injury after routine transnasal rhinological surgery.
AB  - OBJECTIVES: Routine transnasal rhinological procedures are widely practiced and
      are considered as safe, in general. Skull base lesions occur in less than 1% of
      procedures and typically involve the anterior or middle cranial fossa, while
      clivus lesions have not been well documented. Here we present a series of three
      patients with iatrogenic transclival lesions after routine transnasal
      rhinological procedures. PATIENTS AND METHODS: Three patients with penetrating
      clivus injuries after routine transnasal rhinological procedures were identified.
      All patients had undergone transnasal rhinological surgery at other hospitals and
      two of them were referred for emergency treatment. Patients were managed within
      an interdisciplinary context. RESULTS: There were two women and one man. Mean age
      at surgery was 35 years. All operations had been performed under general
      anaesthesia. In only one instance, perforation of the clivus had been noticed
      during surgery by the ENT physician, while it went unnoticed in the other two
      patients. In one patient, no intracranial injury occurred secondary to the clivus
      fracture, while two patients had extensive brainstem lesions. The first patient
      survived without deficits, but one patient succumbed to the brainstem injury and
      the other remained with severe deficits. Risk factors including anatomical
      variants or distorted morphology were present in all patients. CONCLUSION:
      Transnasal rhinological procedures can result in penetrating clivus injuries,
      which may not be noticed during surgery, but which can result in permanent
      morbidity or mortality. These lesions are obviously very rare and their true
      incidence remains unknown.

PMID- 27050107
TI  - Improved self-management skills predict improvements in quality of life and
      depression in patients with chronic disorders.
AB  - OBJECTIVE: Self-management programs aim to improve patients' skills to manage
      their chronic condition in everyday life. Improvement in self-management is
      assumed to bring about improvements in more distal outcomes, such as quality of
      life. This study aimed to test the hypothesis that changes in self-reported self
      management skills observed after participation in self-management programs
      predict changes in both quality of life and depressive symptoms three months
      later. METHODS: Using latent change modeling, the relationship between changes in
      latent variables over three time points (start and end of rehabilitation, after
      three months) was analysed. The sample comprised 580 patients with different
      chronic conditions treated in inpatient rehabilitation clinics. The influence of
      additional predictor variables (age, sex, perceived social support) and type of
      disorder as a moderator variable was also tested. RESULTS: Changes in self
      reported self-management skills after rehabilitation predicted changes in both
      quality of life and depressive symptoms at the end of rehabilitation and the 3
      months follow-up. These relationships remained significant after the inclusion of
      other predictor variables and were similar across disorders. CONCLUSION: The
      findings provide support for the hypothesis that improvements in proximal
      outcomes of self-management programs may foster improvements in distal outcomes.
      Further studies should investigate treatment mechanisms.

PMID- 27050108
TI  - Altered expression of progesterone receptor isoforms A and B in human eutopic
      endometrium in endometriosis patients.
AB  - Recent data implicate an altered expression of progesterone receptor isoform A
      (PR-A) and B (PR-B) in the endometrium of endometriosis patients. This
      prospective exploratory study aimed to precisely determine the PR-A and PR-B
      expression using immunohistochemical techniques in eutopic endometrium of women
      with endometriosis compared with disease-free women throughout the menstrual
      cycle. All symptomatic patients underwent laparoscopy for the diagnosis of
      endometriosis and histological confirmation of the disease (EO) whereas controls
      were proven disease-free (CO). In CO samples (n=10) an increased expression of PR
      A and PR-B during the proliferative to early secretory phase and a decreased
      expression of both receptor isoforms during the mid to late secretory phase was
      ascertained in accordance with previous studies. In patients with endometriosis
      (n=16) no cycle dependent pattern of PR-A and PR-B expression was identified in
      contrast to patients without endometriosis. Moreover, in EO samples a huge
      variety of inter- and intra-individual differences in PR-A and PR-B expression
      were detected. These data provide further evidence that dysregulation of the PR-A
      and PR-B expression might contribute to the pathophysiology of endometriosis. 

PMID- 27050109
TI  - Examining mindfulness as a predictor of weight loss - Findings from the DIABEGG
      study.
AB  - OBJECTIVE: Identifying individuals who are less likely to respond to a weight
      loss intervention allows better allocation or focus of resources to achieve
      better weight loss results. The current study investigated whether baseline
      levels of mindfulness would predict weight loss during a 12-month diet and
      exercise intervention. METHODS: The Five Facet Mindfulness Questionnaire (FFMQ)
      was administered and body weight measured, at baseline, three, six and 12 months
      in 140 participants with pre-diabetes or type 2 diabetes mellitus and a body mass
      index of >=25kg/m2. 137 of 140 participants completed the FFMQ at baseline and
      were included in this study. RESULTS: There was no correlation between baseline
      mindfulness scores and weight loss. Mean baseline total FFMQ score was 112.2 [95%
      confidence interval: 109.4, 115.1] which did not change over the course of the
      study. Mean baseline body weight was 95.1kg (standard deviation (19.1kg)). There
      was a significant decrease in weight at month 12 (-3.8kg (+/-standard deviation
      5.8kg)). This is comparable to the weight loss achieved by participants in other
      interventions of the same duration. CONCLUSIONS: The findings suggest that
      baseline dispositional mindfulness does not predict the amount of weight loss in
      a lifestyle (diet and exercise) intervention.

PMID- 27050110
TI  - Myxobolus mauriensis n. sp. Infecting Rib Cartilage of Young-of-the-Year River
      Herring in New Jersey: Notes on Pathology, Prevalence, and Genetics.
AB  - :  River herring populations, including Alosa pseudoharengus and Alosa aestivalis
      , have significantly declined as a result of anthropogenic factors throughout
      their range in eastern North America. To better understand the health of the
      species, parasite surveys were conducted in several New Jersey rivers. A novel
      myxozoan parasite, Myxobolus mauriensis n. sp., is described infecting the
      cartilage of pleural ribs in young-of-the-year fish. The parasite forms large
      polysporic plasmodia forming pseudocysts within the ribs, which extend into the
      musculature. Pathology associated with infection includes costochondritis, breaks
      in the rib bones, and deformed bone growth. Rupture of large pseudocysts and
      release of mature spores are associated with myositis, dermatitis, and
      peritonitis. Phylogenetic analysis reveals that M. mauriensis n. sp. occurs in a
      long-branching clade basal to other myxobolids, grouping with several Myxobolus
      species from marine fish (Myxobolus groenlandicus, Myxobolus aeglefini, and
      Myxobolus albi). The closest identity is to M. groenlandicus, with 83% identity
      based on a 1,762-bp sequence of the SSU 18S rDNA. Similarly, spore morphology,
      tropism for cartilage, and association with marine/brackish environments are
      shared in these 4 species. Mature spores of M. mauriensis n. sp. are similar to
      other reported myxobolids, though spores are slightly wider (12.1 +/- 0.44 MUm)
      than long (11.4 +/- 0.44 MUm), with a length:width relationship of 0.94 (+/
      0.04), a feature not commonly described for other species of Myxobolus.
      Prevalence was studied by histology and fresh observation. In both Blueback
      Herring and Alewife, the highest infection prevalence occurred in the Maurice
      River at around 20%, and lower prevalence was found in the Great Egg Harbor River
      at around 5%. In the Delaware River, prevalence was about 2% in Blueback Herring,
      while the parasite was not detected in Alewife samples.

PMID- 27050111
TI  - The cost of vaccination throughout life: A western European overview.
AB  - Despite the interest of policy makers, the actual investment in vaccination is
      poorly documented. Our study assessed the costs of vaccination throughout life
      for a fully immunized Western European citizen. National vaccination calendars
      for England, France, Germany, Italy, Portugal, Spain and Sweden were retrieved.
      We differentiated men from women and healthy individuals from those suffering
      from underlying conditions who require specific additional vaccinations. Vaccine
      costs and administration fees were retrieved from official national source and
      calculated from the national healthcare perspective. Vaccinating an individual
      against up to 17 diseases throughout his entire life and in full compliance with
      national vaccination calendars cost between ?328 and ?2,352 (vaccines costs only)
      and between ?443 and ?3,395 (administration costs included), the lowest range
      corresponds to a healthy man in Sweden and the highest to a woman with underlying
      conditions in England. Vaccination costs varied among countries due to
      heterogeneous national vaccination calendars and organization. In all countries,
      adults (18-64 y) and elderly (>=65 y) accounted for the lowest vaccines costs
      compared with infants (0-24 m) and children/adolescents (2-17 y). In comparison,
      other mass secondary preventive therapies may be at least 3 times more costly.
      Vaccination requires a relatively low level of investment per individual. Our
      estimates should be considered to be the maximum potential costs due to our 100%
      compliance assumption. Increasing coverage rates would bring additional public
      health benefits for a relatively low incremental cost. A life-course approach of
      vaccination should also be encouraged because some missed opportunities remain in
      senior vaccinations.

PMID- 27050112
TI  - Computed Tomographic Findings in Microcephaly Associated with Zika Virus.

PMID- 27050113
TI  - DNA/chitosan electrostatic complex.
AB  - Up to now, chitosan and DNA have been investigated for gene delivery due to
      chitosan advantages. It is recognized that chitosan is a biocompatible and
      biodegradable non-viral vector that does not produce immunological reactions,
      contrary to viral vectors. Chitosan has also been used and studied for its
      ability to protect DNA against nuclease degradation and to transfect DNA into
      several kinds of cells. In this work, high molecular weight DNA is compacted with
      chitosan. DNA-chitosan complex stoichiometry, net charge, dimensions,
      conformation and thermal stability are determined and discussed. The influence of
      external salt and chitosan molecular weight on the stoichiometry is also
      discussed. The isoelectric point of the complexes was found to be directly
      related to the protonation degree of chitosan. It is clearly demonstrated that
      the net charge of DNA-chitosan complex can be expressed in terms of the ratio
      [NH3(+)]/[P(-)], showing that the electrostatic interactions between DNA and
      chitosan are the main phenomena taking place in the solution. Compaction of DNA
      long chain complexed with low molar mass chitosan gives nanoparticles with an
      average radius around 150nm. Stable nanoparticles are obtained for a partial
      neutralization of phosphate ionic sites (i.e.: [NH3(+)]/[P(-)] fraction between
      0.35 and 0.80). 

PMID- 27050114
TI  - Hydroxycinnamic acid bound arabinoxylans from millet brans-structural features
      and antioxidant activity.
AB  - Hydroxycinnamic acid bound arabinoxylans (HCA-AXs) were extracted from brans of
      five Indian millet varieties and response surface methodology was used to
      optimize the extraction conditions. The optimal condition to obtain highest yield
      of millet HCA-AXs was determined as follows: time 61min, temperature 66 degrees
      C, ratio of solvent to sample 12ml/g. Linkage analysis indicated that
      hydroxycinnamic acid bound arabinoxylan from kodo millet (KM-HCA-AX) contained
      comparatively low branched arabinoxylan consisting of 14.6% mono-substituted,
      1.2% di-substituted and 41.2% un-substituted Xylp residues. The HPLC analysis of
      millet HCA-AXs showed significant variation in the content of three major bound
      hydroxycinnamic acids (caffeic, p-coumaric and ferulic acid). The antioxidant
      activity of millet HCA-AXs were evaluated using three in vitro assay methods
      (DPPH, FRAP and beta-carotene linoleate emulsion assays) which suggested both
      phenolic acid composition and structural characteristics of arabinoxylans could
      be correlated to their antioxidant potential, the detailed structural analysis
      revealed that low substituted KM-HCA-AX exhibited relatively higher antioxidant
      activity compared to other medium and highly substituted HCA-AXs from finger
      (FM), proso (PM), barnyard (BM) and foxtail (FOXM) millet. 

PMID- 27050115
TI  - Case Report of Syncope During a Single Pulse Transcranial Magnetic Stimulation
      Experiment in a Healthy Adult Participant.

PMID- 27050116
TI  - Connectivity: An emerging concept for physiotherapy practice.
AB  - Having spent their first century anchored to a biomedical model of practice,
      physiotherapists have been increasingly interested in exploring new models and
      concepts that will better equip them for serving the health-care needs of 21st
      century clients/patients. Connectivity offers one such model. With an extensive
      philosophical background in phenomenology, symbolic interactionism,
      structuralism, and postmodern research, connectivity resists the prevailing
      western biomedical view that health professionals should aim to increase people's
      independence and autonomy, preferring instead to identify and amplify
      opportunities for collaboration and co-dependence. Connectivity critiques the
      normalization that underpins modern health care, arguing that our constant search
      for deviance is building stigma and discrimination into our everyday practice. It
      offers provocative opportunities for physiotherapists to rethink some of the
      fundamental tenets of their profession and better align physiotherapy with 21st
      century societal expectations. In this paper, we provide a background to the
      place connectivity may play in future health care, and most especially future
      physiotherapy practice. The paper examines some of the philosophical antecedents
      that have made connectivity an increasingly interesting and challenging concept
      in health care today. 

PMID- 27050117
TI  - Communication restriction in adults who stutter: Part II.
AB  - This article presents a follow-up study to Lee, van Dulm, Robb, and Ormond
      (2015). The aim was to explore communication restriction in adults with
      stuttering (AWS) using typical language measures and systemic functional
      linguistics (SFL) analyses. The article compared the pre- and post-treatment
      performance of AWS in language productivity and complexity, transitivity,
      modality, appraisal, and theme. Ten-minute conversational samples were obtained
      from 20 AWS before and after participation in intensive stuttering treatment.
      Transcripts were analysed for quantity and complexity of verbal output, and
      frequency of transitivity, modality, appraisal and theme resources. Between pre-
      and post-treatment, the following differences were observed: (1) a significant
      increase in frequency of modal operators, and trends approaching significance for
      (2) increased language complexity (3) increased language expressing appraisal.
      These changes suggest increased flexibility of language use in AWS following
      treatment, particularly towards interpersonal engagement. The value of SFL to
      this area of research is discussed. 

PMID- 27050118
TI  - Changes in Nutrition-Related Behaviors in Alcohol-Dependent Patients After
      Outpatient Detoxification: The Role of Chocolate.
AB  - BACKGROUND: Previous studies have reported changes in nutrition-related behaviors
      in alcohol-dependent patients after alcohol detoxification, but prospective
      studies assessing the effects of these changes on maintaining abstinence are
      lacking. OBJECTIVES: To assess changes in craving and consumption of chocolate
      and other sweets over time up to six months after outpatient alcohol
      detoxification treatment and to detect differences in abstinent versus
      nonabstinent patients. METHODS: One hundred and fifty alcohol-dependent patients
      were included in this prospective observational study. Participants completed
      self-report questionnaires on nutrition-related behaviors and craving before
      detoxification treatment (baseline, t1), one week (t2), one month (t3), and six
      months later (t4). RESULTS: Significant changes in craving for and consumption of
      chocolate as well as in craving for other sweets were observed over time.
      Increases were most prominent within the first month. Patients who remained
      abstinent until t3 consumed three times more chocolate than nonabstainers. One
      quarter of the patients switched from being rare (t1) to frequent (t3) chocolate
      eaters, and 84% of these remained abstinent until t3. No significant correlations
      were found between craving for alcohol and craving for or consumption of
      chocolate or other sweets. CONCLUSIONS/IMPORTANCE: In the first month after
      outpatient alcohol detoxification treatment, significant changes in nutrition
      related behaviors were observed. These changes were not associated with alcohol
      craving. For a subgroup, increasing the frequency of chocolate consumption might
      be a temporary protective factor with respect to alcohol relapse.

PMID- 27050119
TI  - Proximal and proximo-distal bimelic amyotrophy: Evidence of cervical flexion
      induced myelopathy.
AB  - This report aims at describing two new clinical phenotypes associated with
      classical features of cervical flexion induced myelopathy (CFIM). The description
      is of a prospective case series of six young males presenting with progressive
      bilateral proximal/proximo-distal amyotrophy of upper limbs and demonstrating the
      typical MRI characteristics of Hirayama disease. All underwent detailed clinical,
      electrophysiologcal and imaging studies. The affected muscles were shoulder
      girdles and arms in proximal form (n = 2) and the entire upper limbs in proximo
      distal form (n = 4). The mean age at onset was 21.0 +/- 3.3 years, duration of
      illness was 6.7 +/- 3.4 years, period of progression was 39.0 +/- 27.3 months
      followed by a stable phase of 45.0 +/- 50.0 months. All had severe wasting and
      weakness of affected muscles leading to significant disability. Nerve conduction
      studies revealed grossly reduced compound muscle action potential amplitudes with
      neurogenic pattern on electromyography of affected muscles. On MRI all revealed
      evidence of cervical cord atrophy with signal changes, dural detachment and
      extensive posterior epidural enhancement (variably from C1 to T2 level). Altered
      cervical curvature was prominent. In conclusion, hitherto unreported, we describe
      two additional clinical phenotypes (proximal and proximo-distal forms) of
      Hirayama disease demonstrating the cardinal imaging features of CFIM.

PMID- 27050120
TI  - A novel non-thermostable deuterolysin from Aspergillus oryzae.
AB  - Three putative deuterolysin (EC 3.4.24.29) genes (deuA, deuB, and deuC) were
      found in the Aspergillus oryzae genome database (
      http://www.bio.nite.go.jp/dogan/project/view/AO ). One of these genes, deuA, was
      corresponding to NpII gene, previously reported. DeuA and DeuB were overexpressed
      by recombinant A. oryzae and were purified. The degradation profiles against
      protein substrates of both enzymes were similar, but DeuB showed wider substrate
      specificity against peptidyl MCA-substrates compared with DeuA. Enzymatic
      profiles of DeuB except for thermostability also resembled those of DeuA. DeuB
      was inactivated by heat treatment above 80 degrees  C, different from
      thermostable DeuA. Transcription analysis in wild type A. oryzae showed only deuB
      was expressed in liquid culture, and the addition of the proteinous substrate
      upregulated the transcription. Furthermore, the NaNO3 addition seems to eliminate
      the effect of proteinous substrate for the transcription of deuB. 

PMID- 27050121
TI  - Clinical judgement and geriatric assessment for predicting prognosis and
      chemotherapy completion in older patients with a hematological malignancy.
AB  - Prior research has focused on comparing clinical judgment with geriatric
      assessments in identifying potentially unfit patients or the prognostic value of
      geriatric impairments. In this study, we set out to compare and combine geriatric
      impairments with clinical judgment in predicting mortality and non-completion of
      chemotherapy in older patients with a hematological malignancy. Between March
      2004 and August 2014, a multi-dimensional geriatric assessment was performed in
      consecutive patients aged >=65 years diagnosed with a hematological malignancy at
      the Innsbruck university hospital. Associations between geriatric assessment,
      clinical judgment (derived from initial treatment decision) and outcome
      (mortality, non-completion) were analyzed. Patient sample consisted of 157
      patients, of which 37% was 80 + years of age. Aggressive non-Hodgkin lymphoma
      (29%), acute myeloid leukemia (27%) and myelodysplastic syndromes (20%) were most
      common diagnoses. Prevalence of an impaired geriatric assessment (i.e.
      impairments in >=2 of eight assessed domains) was 71% and similar for patients
      receiving standard (71%) or attenuated treatment (72%). Clinical judgment was the
      strongest predictor of mortality (p = 0.003); addition of geriatric assessment
      allowed for further stratification of patients with a good (>75% one year
      survival), intermediate (50-60%) and poor prognosis (<30%). Cumulative burden of
      geriatric impairments further increased risk of mortality. Clinical judgment was
      greatly superior to geriatric assessment in identifying patients at risk for non
      completion. The combination of clinical judgment and geriatric assessment allows
      for better prognostic stratification of patients compared to clinical judgment
      alone.

PMID- 27050122
TI  - Some GCR Polymorphisms (N363S, ER22/23EK, and Bcl-1) May Influence Steroid
      induced Toxicities and Survival Rates in Children With ALL.
AB  - We investigated whether an altered individual glucocorticoid sensitivity due to
      particular glucocorticoid receptor single-nucleotide polymorphisms (SNPs) (N363S,
      ER22/23EK, and Bcl-1) influences the susceptibility to steroid-related
      toxicities, prognostic factors, and survival rates in children with acute
      lymphoblastic leukemia. In total, 346 pediatric patients with acute lymphoblastic
      leukemia were enrolled in our study. Their carrier status was investigated by
      allele-specific polymerase chain reaction analysis. Clinical and laboratory signs
      of glucocorticoid-related toxicities, day-8 prednisone response, 5-year event
      free survival, and 5-year overall survival rates were analyzed and compared
      retrospectively. Hepatotoxicity occurred significantly more often in 363S
      carriers (P=0.004), and glucose metabolism abnormalities were more common in 363S
      carriers (P=0.001), but did not occur in patients with the ER22/23EK SNP.
      Hypertension and central nervous system/behavioral changes did not occur in
      patients with the ER22/23EK SNP. None of the patients with the N363S SNP, the
      ER22/23EK polymorphism, or the GG genotype for the Bcl-1 polymorphism had a poor
      prednisone response. The 363S carriers had significantly better 5-year event-free
      survival (P=0.012) and 5-year overall survival (P=0.013) rates compared with
      noncarriers. The Bcl-1 SNP was not associated with any of the toxicities
      investigated or survival. Children with the N363S polymorphism in the
      glucocorticoid receptor gene were more prone to steroid-related toxicities,
      whereas those with the ER22/23EK polymorphism were less susceptible. Children
      with the N363S polymorphism may have more favorable survival rates.

PMID- 27050123
TI  - Toxicogenomics in drug development: a match made in heaven?

PMID- 27050124
TI  - Exploratory study of acid-forming potential of commercial cheeses: impact of
      cheese type.
AB  - Due to their composition, cheeses are suspected to induce an acid load to the
      body. To better understand this nutritional feature, the acid-forming potential
      of five cheeses from different cheese-making technologies and two milk was
      evaluated on the basis of their potential renal acid load (PRAL) index
      (considering protein, P, Cl, Na, K, Mg and Ca contents) and organic anions
      contents. PRAL index ranged from -0.8 mEq/100 g edible portion for fresh cheese
      to 25.3 mEq/100 g for hard cheese Cantal and 28 mEq/100 g for blue-veined cheese
      Fourme d'Ambert. PRAL values were greatly subjected to interbatch fluctuations.
      This work emphasized a great imbalance between acidifying elements of PRAL
      calculation (Cl, P and proteins elements) and alkalinizing ones (Na and Ca).
      Particularly, Cl followed by P elements had a strong impact on the PRAL value.
      Hard cheeses were rich in lactate, thus, might be less acidifying than suspected
      by their PRAL values only. 

PMID- 27050125
TI  - Automated harvesting and processing of protein crystals through laser
      photoablation.
AB  - Currently, macromolecular crystallography projects often require the use of
      highly automated facilities for crystallization and X-ray data collection.
      However, crystal harvesting and processing largely depend on manual operations.
      Here, a series of new methods are presented based on the use of a low X-ray
      background film as a crystallization support and a photoablation laser that
      enable the automation of major operations required for the preparation of
      crystals for X-ray diffraction experiments. In this approach, the controlled
      removal of the mother liquor before crystal mounting simplifies the cryocooling
      process, in many cases eliminating the use of cryoprotectant agents, while
      crystal-soaking experiments are performed through diffusion, precluding the need
      for repeated sample-recovery and transfer operations. Moreover, the high
      precision laser enables new mounting strategies that are not accessible through
      other methods. This approach bridges an important gap in automation and can
      contribute to expanding the capabilities of modern macromolecular crystallography
      facilities. 

PMID- 27050126
TI  - Novel mode of inhibition by D-tagatose 6-phosphate through a Heyns rearrangement
      in the active site of transaldolase B variants.
AB  - Transaldolase B (TalB) and D-fructose-6-phosphate aldolase A (FSAA) from
      Escherichia coli are C-C bond-forming enzymes. Using kinetic inhibition studies
      and mass spectrometry, it is shown that enzyme variants of FSAA and TalB that
      exhibit D-fructose-6-phosphate aldolase activity are inhibited covalently and
      irreversibly by D-tagatose 6-phosphate (D-T6P), whereas no inhibition was
      observed for wild-type transaldolase B from E. coli. The crystal structure of the
      variant TalB(F178Y) with bound sugar phosphate was solved to a resolution of 1.46
      A and revealed a novel mode of covalent inhibition. The sugar is bound covalently
      via its C2 atom to the E-NH2 group of the active-site residue Lys132. It is
      neither bound in the open-chain form nor as the closed-ring form of D-T6P, but
      has been converted to beta-D-galactofuranose 6-phosphate (D-G6P), a five-membered
      ring structure. The furanose ring of the covalent adduct is formed via a Heyns
      rearrangement and subsequent hemiacetal formation. This reaction is facilitated
      by Tyr178, which is proposed to act as acid-base catalyst. The crystal structure
      of the inhibitor complex is compared with the structure of the Schiff-base
      intermediate of TalB(E96Q) formed with the substrate D-fructose 6-phosphate
      determined to a resolution of 2.20 A. This comparison highlights the differences
      in stereochemistry at the C4 atom of the ligand as an essential determinant for
      the formation of the inhibitor adduct in the active site of the enzyme.

PMID- 27050127
TI  - Direct-methods structure determination of a trypanosome RNA-editing substrate
      fragment with translational pseudosymmetry.
AB  - Using direct methods starting from random phases, the crystal structure of a 32
      base-pair RNA (675 non-H RNA atoms in the asymmetric unit) was determined using
      only the native diffraction data (resolution limit 1.05 A) and the computer
      program SIR2014. The almost three helical turns of the RNA in the asymmetric unit
      introduced partial or imperfect translational pseudosymmetry (TPS) that modulated
      the intensities when averaged by the l Miller indices but still escaped automated
      detection. Almost six times as many random phase sets had to be tested on average
      to reach a correct structure compared with a similar-sized RNA hairpin (27
      nucleotides, 580 non-H RNA atoms) without TPS. More sensitive methods are needed
      for the automated detection of partial TPS.

PMID- 27050128
TI  - Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from
      Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae
      complex.
AB  - Klebsiella pneumoniae is a Gram-negative bacterium that is responsible for a
      range of common infections, including pulmonary pneumonia, bloodstream infections
      and meningitis. Certain strains of Klebsiella have become highly resistant to
      antibiotics. Despite the vast amount of research carried out on this class of
      bacteria, the molecular structure of its topoisomerase IV, a type II
      topoisomerase essential for catalysing chromosomal segregation, had remained
      unknown. In this paper, the structure of its DNA-cleavage complex is reported at
      3.35 A resolution. The complex is comprised of ParC breakage-reunion and ParE
      TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by
      levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. This complex
      is compared with a similar complex from Streptococcus pneumoniae, which has
      recently been solved.

PMID- 27050129
TI  - UHM-ULM interactions in the RBM39-U2AF65 splicing-factor complex.
AB  - RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co
      activator of estrogen receptors and Jun/AP-1, and its function has been
      associated with malignant progression in a number of cancers. The C-terminal RRM
      domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate
      protein-protein interactions through a short tryptophan-containing peptide known
      as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the
      RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are
      reported. The RBM39-U2AF65 interaction was confirmed by co-immunoprecipitation
      from human cell extracts, by isothermal titration calorimetry and by NMR chemical
      shift perturbation experiments with the purified proteins. When compared with
      related complexes, such as U2AF35-U2AF65 and RBM39-SF3b155, the RBM39-UHM-U2AF65
      ULM complex reveals both common and discriminating recognition elements in the
      UHM-ULM binding interface, providing a rationale for the known specificity of UHM
      ULM interactions. This study therefore establishes a structural basis for
      specific UHM-ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39
      and SF3b155, and a platform for continued studies of intermolecular interactions
      governing disease-related alternative splicing in eukaryotic cells. 

PMID- 27050130
TI  - Grappling with anisotropic data, pseudo-merohedral twinning and pseudo
      translational noncrystallographic symmetry: a case study involving pyruvate
      kinase.
AB  - Pyruvate kinase is a key regulatory enzyme involved in the glycolytic pathway.
      The crystal structure of Escherichia coli type I pyruvate kinase was first solved
      in 1995 at 2.5 A resolution. However, the space group was ambiguous, being either
      primitive orthorhombic (P2(1)2(1)2(1)) or C-centred orthorhombic (C222(1)). Here,
      the structure determination and refinement of E. coli type I pyruvate kinase to
      2.28 A resolution are presented. Using the same crystallization conditions as
      reported previously, the enzyme was found to crystallize in space group P2(1).
      Determination of the space group was complicated owing to anisotropic data,
      pseudo-translational noncrystallographic symmetry and the pseudo-merohedrally
      twinned nature of the crystal, which was found to have very close to 50%
      twinning, leading to apparent orthorhombic symmetry and absences that were not
      inconsistent with P2(1)2(1)2(1). The unit cell contained two tetramers in the
      asymmetric unit (3720 residues) and, when compared with the orthorhombic
      structure, virtually all of the residues could be easily modelled into the
      density. Averaging of reflections into the lower symmetry space group with
      twinning provided tidier electron density that allowed ~30 missing residues of
      the lid domain to be modelled for the first time. Moreover, residues in a
      flexible loop could be modelled and sulfate molecules are found in the allosteric
      binding domain, identifying the pocket that binds the allosteric activator
      fructose 1,6-bisphosphate in this isozyme for the first time. Lastly, we note the
      pedagogical benefits of difficult structures to emerging crystallographers.

PMID- 27050131
TI  - Microcrystal delivery by pulsed liquid droplet for serial femtosecond
      crystallography.
AB  - A liquid-droplet injector has been developed that delivers pristine microcrystals
      to an X-ray irradiation area for conducting serial femtosecond crystallography
      (SFX) with an X-ray free-electron laser (XFEL). By finely tuning the pulsed
      liquid droplets in time and space, a high hit rate of the XFEL pulses to
      microcrystals in the droplets was achieved for measurements using 5 um tetragonal
      lysozyme crystals, which produced 4265 indexable diffraction images in about 30
      min. The structure was determined at a resolution of 2.3 A from <0.3 mg of
      protein. With further improvements such as reduction of the droplet size, liquid
      droplets have considerable potential as a crystal carrier for SFX with low sample
      consumption.

PMID- 27050132
TI  - New conformations of linear polyubiquitin chains from crystallographic and
      solution-scattering studies expand the conformational space of polyubiquitin.
AB  - The conformational flexibility of linkage-specific polyubiquitin chains enables
      ubiquitylated proteins and their receptors to be involved in a variety of
      cellular processes. Linear or Met1-linked polyubiquitin chains, associated with
      nondegradational cellular signalling pathways, have been known to adopt multiple
      conformations from compact to extended conformations. However, the extent of such
      conformational flexibility remains open. Here, the crystal structure of linear
      Ub2 was determined in a more compact conformation than that of the previously
      known structure (PDB entry 3axc). The two structures differ significantly from
      each other, as shown by an r.m.s.d. between C(alpha) atoms of 3.1 A. The
      compactness of the linear Ub2 structure in comparison with PDB entry 3axc is
      supported by smaller values of the radius of gyration (Rg; 18 versus 18.9 A) and
      the maximum interatomic distance (Dmax; 55.5 versus 57.8 A). Extra intramolecular
      hydrogen bonds formed among polar residues between the distal and proximal
      ubiquitin moieties seem to contribute to stabilization of the compact
      conformation of linear Ub2. An ensemble of three semi-extended and extended
      conformations of linear Ub2 was also observed by small-angle X-ray scattering
      (SAXS) analysis in solution. In addition, the conformational heterogeneity in
      linear polyubiquitin chains is clearly manifested by SAXS analyses of linear Ub3
      and Ub4: at least three distinct solution conformations are observed in each
      chain, with the linear Ub3 conformations being compact. The results expand the
      extent of conformational space of linear polyubiquitin chains and suggest that
      changes in the conformational ensemble may be pivotal in mediating multiple
      signalling pathways.

PMID- 27050133
TI  - T-to-R switch of muscle fructose-1,6-bisphosphatase involves fundamental changes
      of secondary and quaternary structure.
AB  - Fructose-1,6-bisphosphatase (FBPase) catalyzes the hydrolysis of fructose 1,6
      bisphosphate to fructose 6-phosphate and is a key enzyme of gluconeogenesis and
      glyconeogenesis and, more generally, of the control of energy metabolism and
      glucose homeostasis. Vertebrates, and notably Homo sapiens, express two FBPase
      isoforms. The liver isozyme is expressed mainly in gluconeogenic organs, where it
      functions as a regulator of glucose synthesis. The muscle isoform is expressed in
      all cells, and recent studies have demonstrated that its role goes far beyond the
      enzymatic function, as it can interact with various nuclear and mitochondrial
      proteins. Even in its enzymatic function, the muscle enzyme is different from the
      liver isoform, as it is 100-fold more susceptible to allosteric inhibition by AMP
      and this effect can be abrogated by complex formation with aldolase. All FBPases
      are homotetramers composed of two intimate dimers: the upper dimer and the lower
      dimer. They oscillate between two conformational states: the inactive T form when
      in complex with AMP, and the active R form. Parenthetically, it is noted that
      bacterial FBPases behave somewhat differently, and in the absence of allosteric
      activators exist in a tetramer-dimer equilibrium even at relatively high
      concentrations. [Hines et al. (2007), J. Biol. Chem. 282, 11696-11704]. The T-to
      R transition is correlated with the conformation of the key loop L2, which in the
      T form becomes 'disengaged' and unable to participate in the catalytic mechanism.
      The T states of both isoforms are very similar, with a small twist of the upper
      dimer relative to the lower dimer. It is shown that at variance with the well
      studied R form of the liver enzyme, which is flat, the R form of the muscle
      enzyme is diametrically different, with a perpendicular orientation of the upper
      and lower dimers. The crystal structure of the muscle-isozyme R form shows that
      in this arrangement of the tetramer completely new protein surfaces are exposed
      that are most likely targets for the interactions with various cellular and
      enzymatic partners. The cruciform R structure is stabilized by a novel 'leucine
      lock', which prevents the key residue, Asp187, from locking loop L2 in the
      disengaged conformation. In addition, the crystal structures of muscle FBPase in
      the T conformation with and without AMP strongly suggest that the T-to-R
      transition is a discrete jump rather than a shift of an equilibrium smooth
      transition through multiple intermediate states. Finally, using snapshots from
      three crystal structures of human muscle FBPase, it is conclusively demonstrated
      that the AMP-binding event is correlated with a beta->alpha transition at the N
      terminus of the protein and with the formation of a new helical structure. 

PMID- 27050134
TI  - Phase improvement via the Phantom Derivative technique: ancils that are related
      to the target structure.
AB  - Density modification is a general standard technique which may be used to improve
      electron density derived from experimental phasing and also to refine densities
      obtained by ab initio approaches. Here, a novel method to expand density
      modification is presented, termed the Phantom derivative technique, which is
      based on non-existent structure factors and is of particular interest in
      molecular replacement. The Phantom derivative approach uses randomly generated
      ancil structures with the same unit cell as the target structure to create non
      existent derivatives of the target structure, called phantom derivatives, which
      may be used for ab initio phasing or for refining the available target structure
      model. In this paper, it is supposed that a model electron density is available:
      it is shown that ancil structures related to the target obtained by shifting the
      target by origin-permissible translations may be employed to refine model phases.
      The method enlarges the concept of the ancil, is as efficient as the canonical
      approach using random ancils and significantly reduces the CPU refinement time.
      The results from many real test cases show that the proposed methods can
      substantially improve the quality of electron-density maps from molecular
      replacement-based phases. 

PMID- 27050135
TI  - Diffraction-geometry refinement in the DIALS framework.
AB  - Rapid data collection and modern computing resources provide the opportunity to
      revisit the task of optimizing the model of diffraction geometry prior to
      integration. A comprehensive description is given of new software that builds
      upon established methods by performing a single global refinement procedure,
      utilizing a smoothly varying model of the crystal lattice where appropriate. This
      global refinement technique extends to multiple data sets, providing useful
      constraints to handle the problem of correlated parameters, particularly for
      small wedges of data. Examples of advanced uses of the software are given and the
      design is explained in detail, with particular emphasis on the flexibility and
      extensibility it entails. 

PMID- 27050136
TI  - A pipeline for structure determination of in vivo-grown crystals using in cellulo
      diffraction.
AB  - While structure determination from micrometre-sized crystals used to represent a
      challenge, serial X-ray crystallography on microfocus beamlines at synchrotron
      and free-electron laser facilities greatly facilitates this process today for
      microcrystals and nanocrystals. In addition to typical microcrystals of purified
      recombinant protein, these advances have enabled the analysis of microcrystals
      produced inside living cells. Here, a pipeline where crystals are grown in insect
      cells, sorted by flow cytometry and directly analysed by X-ray diffraction is
      presented and applied to in vivo-grown crystals of the recombinant CPV1
      polyhedrin. When compared with the analysis of purified crystals, in cellulo
      diffraction produces data of better quality and a gain of ~0.35 A in resolution
      for comparable beamtime usage. Importantly, crystals within cells are readily
      derivatized with gold and iodine compounds through the cellular membrane. Using
      the multiple isomorphous replacement method, a near-complete model was autobuilt
      from 2.7 A resolution data. Thus, in favourable cases, an in cellulo pipeline can
      replace the complete workflow of structure determination without compromising the
      quality of the resulting model. In addition to its efficiency, this approach
      maintains the protein in a cellular context throughout the analysis, which
      reduces the risk of disrupting transient or labile interactions in protein
      protein or protein-ligand complexes.

PMID- 27050139
TI  - A first-in-human, double-blind, randomised, placebo-controlled, dose ascending
      study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee
      osteoarthritis.
AB  - OBJECTIVES: To evaluate the safety of intra-articular sprifermin (primary), and
      to evaluate systemic exposure, biomarkers, histology, and other cartilage
      parameters in patients with advanced osteoarthritis (OA). METHODS: This was a
      first-in-human, double-blind, randomised, placebo-controlled trial of single and
      multiple ascending doses of sprifermin from 3-300 MUg in knee OA patients
      scheduled for total knee replacement. Patients were randomised 3:1 to sprifermin
      or placebo, injected into the target knee once or once weekly for 3 weeks, and
      followed-up for 24 weeks. RESULTS: Fifty-five patients were treated with
      sprifermin, 25 with single and 30 with multiple doses, 18 received placebo. There
      was no clear difference between the active and placebo groups in incidence,
      severity, and nature of reported treatment emergent adverse events. Acute
      inflammatory reactions were slightly more common with sprifermin 300 MUg, but
      none led to discontinuation. No clear difference was seen between placebo and
      sprifermin in physician-assessed local tolerability, pain, or swelling in the
      knee. No meaningful changes over time, or differences between treatment groups,
      were observed for safety laboratory parameters or ECG. Although individual
      abnormalities were observed, no patterns were evident suggesting a relation to
      treatment or potential safety concern. No systemic sprifermin exposure, anti
      FGF18 antibodies, or clear-cut effects on systemic biomarkers were detected.
      CONCLUSIONS: This first clinical trial of sprifermin revealed no serious safety
      concerns, although larger studies are needed. The possibility of positive effects
      of intra-articular sprifermin on histological and other cartilage parameters in
      knee OA also warrant further investigation.

PMID- 27050137
TI  - XModeScore: a novel method for accurate protonation/tautomer-state determination
      using quantum-mechanically driven macromolecular X-ray crystallographic
      refinement.
AB  - Gaining an understanding of the protein-ligand complex structure along with the
      proper protonation and explicit solvent effects can be important in obtaining
      meaningful results in structure-guided drug discovery and structure-based drug
      discovery. Unfortunately, protonation and tautomerism are difficult to establish
      with conventional methods because of difficulties in the experimental detection
      of H atoms owing to the well known limitations of X-ray crystallography. In the
      present work, it is demonstrated that semiempirical, quantum-mechanics-based
      macromolecular crystallographic refinement is sensitive to the choice of a
      protonation-state/tautomer form of ligands and residues, and can therefore be
      used to explore potential states. A novel scoring method, called XModeScore, is
      described which enumerates the possible protomeric/tautomeric modes, refines each
      mode against X-ray diffraction data with the semiempirical quantum-mechanics
      (PM6) Hamiltonian and scores each mode using a combination of energetic strain
      (or ligand strain) and rigorous statistical analysis of the difference electron
      density distribution. It is shown that using XModeScore it is possible to
      consistently distinguish the correct bound protomeric/tautomeric modes based on
      routine X-ray data, even at lower resolutions of around 3 A. These X-ray results
      are compared with the results obtained from much more expensive and laborious
      neutron diffraction studies for three different examples: tautomerism in the
      acetazolamide ligand of human carbonic anhydrase II (PDB entries 3hs4 and 4k0s),
      tautomerism in the 8HX ligand of urate oxidase (PDB entries 4n9s and 4n9m) and
      the protonation states of the catalytic aspartic acid found within the active
      site of an aspartic protease (PDB entry 2jjj). In each case, XModeScore applied
      to the X-ray diffraction data is able to determine the correct protonation state
      as defined by the neutron diffraction data. The impact of QM-based refinement
      versus conventional refinement on XModeScore is also discussed.

PMID- 27050140
TI  - [Minimum Caseload Requirements and In-hospital Mortality: Observational Study
      using Nationwide Hospital Discharge Data from 2006 to 2013].
AB  - Background: In order to improve hospital care, minimum caseload requirements for
      certain elective hospital treatments have been defined by law in Germany. This
      study analyses retrospectively if adherence to this regulation is associated with
      the outcome of hospital treatment. Differences in in-hospital mortality were
      analyzed for complex esophageal and pancreatic surgery, liver and kidney
      transplantation, stem cell transplantation and total knee replacement. Methods:
      Within individual inpatient data of the nationwide German hospital discharge data
      (DRG statistics) all inpatient episodes subject to the minimum volume
      requirements were identified and annual caseloads per hospital were calculated.
      Inpatient episodes were assigned to 2 groups: Patients treated in hospitals with
      a caseload equal to or greater than the minimum caseload (>= MC) and patients
      treated in hospitals with a caseload below the minimum caseload (< MC). Logistic
      regression was used to calculate adjusted in-hospital mortality. Results: In
      total, 28 931 esophageal surgeries, 78 879 pancreatic surgeries, 7 984 liver
      transplantations, 21 773 kidney transplantations, 51 064 stem cell
      transplantations and 1 093 296 total knee replacements were analyzed. Adjusted in
      hospital mortality in hospitals with a caseload>=MC was significantly lower than
      in hospitals with a caseload<MC for esophageal surgery (9.2% [95% KI 8.8-9,6] vs.
      12.1% [11.4-12.9]), pancreatic surgery (8.6% [8.3-8.8] vs. 11.8% [11.2-12.5]),
      kidney transplantation (1.7% [1.4-1.8] vs. 3.3% [2.1-5.0]) and total knee
      replacement (0.13% [0.12-0.14] vs. 0.18% [0.14-0.23]). For liver transplantation,
      no significant difference in adjusted mortality was found (15.5% [14.7-16.5] vs.
      15.9% [12.9-19.3]). For stem cell transplantation mortality in hospitals with a
      caseload>=MC was significantly higher than in hospital with a caseload<MC (6.0%
      [5.7-6.2] vs. 4.0% [3.2-4.9]). Conclusion: For 4 of the 6 studied treatments, a
      significantly lower risk of in-hospital death was observed in hospitals that
      adhere to the minimum caseload requirement. This implies that, for those
      treatments, full implementation of the minimum caseload regulation could improve
      the quality of hospital care in Germany.

PMID- 27050142
TI  - A Risk-Reduction Program for Patients With Peripheral Arterial Disease: Who
      Benefits and Why?

PMID- 27050141
TI  - Human Determinants and the Role of Melanocortin-1 Receptor Variants in Melanoma
      Risk Independent of UV Radiation Exposure.
AB  - IMPORTANCE: Despite the unquestioned relationship of UV radiation (UVR) exposure
      and melanoma development, UVR-independent development of melanoma has only
      recently been described in mice. These findings in mice highlight the importance
      of the genetic background of the host and could be relevant for preventive
      measures in humans. OBJECTIVE: To study the role of the melanocortin-1 receptor
      (MC1R) and melanoma risk independently from UVR in a clinical setting. DESIGN,
      SETTING, AND PARTICIPANTS: Hospital-based case-control study, including genetic
      testing, questionnaires, and physical data (Molecular Markers of Melanoma Study
      data set) including 991 melanoma patients (cases) and 800 controls. MAIN OUTCOMES
      AND MEASURES: Association of MC1R variants and melanoma risk independent from sun
      exposure variables. RESULTS: The 1791 participants included 991 with a diagnosis
      of melanoma and 800 control patients (mean [SD] age, 59.2 [15.6] years; 50.5%
      male). Compared with wild-type carriers, carriers of MC1R variants were at higher
      melanoma risk after statistically adjusting for previous UVR exposure
      (represented by prior sunburns and signs of actinic skin damage identified by
      dermatologists), age, and sex compared with wild-type carriers (>=2 variants, OR,
      2.13 [95% CI, 1.66-2.75], P < .001; P for trend <.001). After adjustment for sex,
      age, sunburns in the past, and signs of actinic skin damage, the associations
      remained significant (OR, 1.65 [95% CI, 1.02-2.67] for R/R, OR, 2.63 [95% CI,
      1.82-3.81] for R/r; OR, 1.83 [95% CI, 1.36-2.48] for R/0; and OR, 1.50 [95% CI,
      1.01-2.21] for r/r, with P values ranging from <.001 to .04 when adjusted for
      facial actinic skin damage; OR, 2.36 [95% CI, 1.62-3.43] for R/r; and OR, 1.47
      [95% CI, 1.08-1.99] for R/0 with P values ranging from <.001 to .01 when adjusted
      for dorsal actinic skin damage; and OR, 2.54 [95% CI, 1.76-3.67] for R/r, OR,
      1.75 [95% CI, 1.30-2.36] for R/0; and OR, 1.50 [95% CI, 1.02-2.20] for r/r with P
      values ranging from <.001 to .04 when adjusted for actinic skin damage on the
      hands). CONCLUSIONS AND RELEVANCE: Carriers of MC1R variants were at increased
      melanoma risk independent of their sun exposure. Further studies are required to
      elucidate the causes of melanoma development in these individuals.

PMID- 27050143
TI  - Photoreactivation and dark repair of environmental E. coli strains following 24
      kHz continuous ultrasound and UV-C irradiation.
AB  - In this study, effects of 24 kHz continuous ultrasound and UV-C on inactivation
      and potential repair of environmental E. coli strains were studied through a
      culture based method and a metabolic activity assay. Three environmental E. coli
      strains isolated from fecal samples of feral hog and deer and treated wastewater
      effluent were studied and compared with a laboratory E. coli strain (ATCC(r)
      10798). Metabolic activity of E. coli cells during the inactivation and repair
      period was assessed using the AlamarBlue(r) assay. Transmission electron
      microscopy assays were also performed to evaluate morphological damage of
      bacterial cell wall. After 24 h of photoreactivation period, laboratory E. coli
      strain (ATCC(r) 10798) reactivated by 30% and 42% in contrast to E. coli isolate
      from treated wastewater effluent, which reactivated by 53% and 82% after
      ultrasound and UV-C treatment, respectively. Possible shearing and reduction in
      cell size of E. coli strains exposed to ultrasound was revealed by transmission
      electron micrographs. Metabolic activity of E. coli strains was greatly reduced
      due to morphological damage to cell membrane caused by 24 kHz continuous
      ultrasound. Based upon experimental data and TEM micrographs, it could be
      concluded that ultrasound irradiation has potential in advanced water treatment
      and water reuse applications. 

PMID- 27050144
TI  - Bio-assay guided identification of hepatoprotective polyphenols from Penthorum
      chinense Pursh on t-BHP induced oxidative stress injured L02 cells.
AB  - Penthorum chinense Pursh (Ganhuangcao in Chinese) is traditionally used for liver
      protection and treatment of liver diseases, including hepatitis B, hepatitis C
      and alcoholic liver damage. We and others have disclosed the hepatoprotective
      effect of different extracts from P. chinense. To further explore the chemical
      principles responsible for its liver protective effect, a bioactivity guided
      isolation was carried out on the water extract of P. chinense, which led to the
      identification of an effective fraction (E50M60). Further isolation of the E50M60
      fraction produced ten polyphenols. Among them, quercetin showed the most
      significant protective effect on tert-butyl hydroperoxide (t-BHP) induced
      hepatocyte damage. Further study demonstrated that both the E50M60 fraction and
      quercetin attenuated t-BHP induced hepatocyte apoptosis through up-regulating the
      expression of B-cell lymphoma-2 protein (BCL-2) and BCL-xL, and down-regulating
      the cleaved products of caspase-7, -9 and nuclear poly(ADP-ribose) polymerase
      (PARP). Moreover, the E50M60 fraction and quercetin promoted nuclear factor-like
      2 (NRF2), superoxide dismutase-2 (SOD-2) and heme oxygenase-1 (HO-1) expressions
      and suppressed Kelch-like ECH-associated protein 1 (KEAP-1) expression, resulting
      in resistance to the reactive oxygen species (ROS) induced mitochondrial
      oxidative stress. Altogether, both the active fraction and quercetin from P.
      chinense might be well developed as a novel functional food for liver protection.

PMID- 27050145
TI  - Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal
      cancer.
AB  - PRSS8 is a membrane-anchored serine protease prostasin and has been shown an
      association with carcinogenesis. Herein we found that PRSS8 expression was
      significantly reduced in colorectal adenomas and adenocarcinomas. The decreased
      PRSS8 was well correlated with clinical stages, poor differentiation and shorter
      survival time of colorectal cancer. Furthermore, increase of PRSS8 led to the
      inhibition of colorectal cancer cell proliferation, knockdown of PRSS8
      accelerated cell proliferation in vitro, and overexpressing PRSS8 retarded cancer
      cell growth in nude mice. Mechanistic studies revealed that PRSS8 inhibited
      Sphk1/S1P/Stat3/Akt signaling pathway, in terms of inverse association between
      PRSS8 and Sphk1 in human colorectal cancers and in Sphk1-/- mice. In conclusion,
      PRSS8 acts as a tumor suppressor by inhibiting Sphk1/S1P/Stat3/Akt signaling
      pathway, and could be used as a biomarker to monitor colorectal carcinogenesis
      and predict outcomes. 

PMID- 27050146
TI  - Pre-miRNA variants as predictors of clinical outcome in patients with squamous
      cell carcinomas of the nonoropharynx.
AB  - Functional polymorphisms of miRNAs may affect the function and target expression
      of miRNAs, which can, in turn, affect the biological activity, etiology, and
      prognosis of cancer. We hypothesized that four common polymorphisms in pre-miRNAs
      (hsa-mir-146a rs2910164 G > C, hsa-mir-196a2 rs11614913 C > T, hsa-mir-149
      rs2292832 G > T, and hsa-mir-499 rs3746444 A > G) are associated with survival in
      SCCNOP. We used univariate and multivariable Cox models to evaluate the
      associations between the four polymorphisms and survival. We found that hsa-mir
      149 rs2292832 and hsa-mir-499 rs3746444 had statistically significant
      associations with survival, but hsa-mir-146a rs2910164 and hsa-mir-196a2
      rs11614913 did not. Patients having the hsa-mir-149 CC and hsa-mir-499 TT wild
      type genotypes had significantly better overall, disease-specific, and disease
      free survival compared with those who had the corresponding variant CT/TT and
      CT/CC genotypes, respectively. Furthermore, these genotypes were significantly
      associated with reduced risk of overall death, death owing to disease, and
      recurrence after adjustment for important prognostic confounders, indicating that
      these pre-miRNA polymorphisms may be prognostic biomarkers for SCCNOP. Moreover,
      the stratified analyses based on smoking status and treatment indicated that the
      effects of hsa-mir-149 and hsa-mir-499 polymorphisms on survival were more
      pronounced in ever smokers and patients treated with chemoradiation. Our findings
      support that the hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 polymorphisms
      play a significant role in the prognosis of SCCNOP, especially in smokers and
      patients treated with chemoradiation. Prospective studies with larger sample
      sizes are needed to confirm these findings. 

PMID- 27050147
TI  - Matrix stiffness-mediated effects on stemness characteristics occurring in HCC
      cells.
AB  - Matrix stiffness as an important physical attribute of extracellular matrix
      exerts significant impacts on biological behaviors of cancer cells such as
      growth, proliferation, motility, metabolism and invasion. However, its influence
      on cancer stemness still remains elusive. Here, we explore whether matrix
      stiffness-mediated effects on stemness characteristics occur in HCC cells. As the
      substrate stiffness increased, HCC cells exhibited high proportion of cells with
      CD133(+)/EpCAM(+), high expression levels of CD133, EpCAM, Nanog and SOX2,
      greater self-renewing ability and oxaliplatin resistance. Simultaneously, their
      phosphorylation levels of Akt and mTOR, as well as p-4E-BP and SOX2 expressions
      were also obviously upregulated. Conversely, knockdown of integrin beta1
      partially attenuated higher stiffness-mediated stemness characteristics in HCC
      cells, and reversed the phosphorylation levels of Akt and mTOR, and expressions
      of p-4E-BP and SOX2, suggesting that integrin beta1 may deliver higher stiffness
      signal into HCC cells and activate mTOR signaling pathway. Additionally, mTOR
      inhibitor suppressed the mTOR phosphorylation level and expression levels of p-4E
      BP and SOX2 in HCC cells grown on higher stiffness substrate, as well as
      depressed their stemness properties significantly, favoring a regulating role of
      mTOR signaling pathway in matrix stiffness-mediated effects on stemness. In
      summary, matrix stiffness may be involved in the process of stemness regulation
      via activating integrin beta1/Akt/mTOR/SOX2 signaling pathway. To the best of our
      knowledge, this study first reveals a novel regulating pathway to direct the
      stemness characteristics in HCC cells. 

PMID- 27050148
TI  - Treatment outcome of nimotuzumab plus chemotherapy in advanced cancer patients: a
      single institute experience.
AB  - Nimotuzumab is a humanized anti-EGFR IgG1 monoclonal antibody and demonstrates a
      better safety profile than other anti-EGFR antibodies due to its intermediate
      affinity. Since it was approved in China for the treatment of nasopharyngeal
      cancer (NPC), it has been widely used in NPC and in many clinical trials for
      other cancer types. However, the optimal dose and administration frequency of
      nimotuzumab that should be used and which kind of cancer patients will be more
      benefited from nimotuzumab is still unknown. In this retrospective study, 205
      advanced cancer patients with colorectal cancer, esophageal cancer, head and neck
      cancer, gastric cancer, non-small cell lung cancer, or other cancers from
      mainland China, treated with nimotuzumab in combination with chemotherapy, were
      enrolled. Over 60% of these patients received nimotuzumab > 6 doses and >= 400
      mg/week as maintenance therapy. It was well tolerated in real-life patients. This
      report demonstrates that age, sex and previous treatment might be potential
      predictive factors for survival, and patients received nimotuzumab > 6 doses and
      > 200 mg/week might benefit more from nimotuzumab therapy. Using these factors
      for stratification analysis may form a predictive differential clinical strategy
      for nimotuzumab to maximize the benefit in patients with different epithelial
      tumors. 

PMID- 27050149
TI  - Promoter methylation of RNF180 is associated with H.pylori infection and serves
      as a marker for gastric cancer and atrophic gastritis.
AB  - Promoter methylation (PM) of RING-finger protein (RNF) 180 affects gastric cancer
      (GC) prognosis, but its association with risk of GC or atrophic gastritis (AG) is
      unclear. We investigated relationships between RNF180 PM and GC or AG, and the
      effects of Helicobactor pylori (H.pylori) infection on RNF180 PM. This study
      included 513 subjects (159 with GC, 186 with AG, and 168 healthy controls [CON])
      for RNF180 PM analysis, and another 55 GC patients for RNF180 gene expression
      analysis. Methylation was quantified using average methylation rates (AMR),
      methylated CpG site counts (MSC) and hypermethylated CpG site counts (HSC).
      RNF180 promoter AMR and MSC increased with disease severity. Optimal cut-offs
      were GC + AG: AMR > 0.153, MSC > 4 or HSC > 1; GC: AMR > 0.316, MSC > 15 and HSC
      > 6. Hypermethylation at 5 CpG sites differed significantly between GC/AG and CON
      groups, and was more common in GC patients than AG and CON groups for 2 other CpG
      sites. The expression of RNF180 mRNA levels in tumor were significantly lower
      than those in non-tumor, with the same as in hypermethylation than
      hypomethylation group. H.pylori infection increased methylation in normal tissue
      or mild gastritis, and increased hypermethylation risk at 3 CpG sites in AG. In
      conclusion, higher AMR, MSC and HSC levels could identify AG + GC or GC. Some
      RNF180 promoter CpG sites could identify precancerous or early-stage GC. H.pylori
      affects RNF180 PM in normal tissue or mild gastritis, and increases
      hypermethylation in 3 CpG sites in AG. 

PMID- 27050150
TI  - The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in
      pancreatic cancer.
AB  - Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act
      oncogenically. In this study, one-step quantitative real-time polymerase chain
      reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed
      to evaluate the relationship between Trop2 expression and the clinicopathological
      features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated
      with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This
      Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence
      assay. MTT and wound healing analyses were used to evaluate the inhibitory effect
      of Trop2Fab-DOX on PC cell growth in vitro, while xenograft nude mice model was
      established to examine the tumor-inhibitory effects of PC in vivo. High Trop2
      expression was observed in PC tissues and Trop2 expression was associated with
      several malignant attributes of PC patients, including overall survival. Trop2Fab
      DOX can bind to the Trop2-expressing PC cells and provide an improved releasing
      type of DOX. In addition, Trop2Fab-DOX inhibited the proliferation and suppressed
      the migration of PC cells in a dose-dependent manner in vitro, while inhibited
      the growth of PC xenografts in vivo. Trop2 is a specific marker for PC, and a
      novel Trop2Fab-DOX ADC has a potent antitumor activity. 

PMID- 27050151
TI  - Genetically-defined novel oral squamous cell carcinoma cell lines for the
      development of molecular therapies.
AB  - Emerging biological and translational insights from large sequencing efforts
      underscore the need for genetically-relevant cell lines to study the
      relationships between genomic alterations of tumors, and therapeutic
      dependencies. Here, we report a detailed characterization of a novel panel of
      clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from
      patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and
      copy number alterations (CNA) identified that the cell lines harbour CNA that
      have been previously reported in OSCC, for example focal amplications in 3q, 7p,
      8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified
      the same cohort of frequently mutated genes previously reported in OSCC including
      TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified
      mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that
      may be associated with this specific risk factor. Gene expression profiles of the
      ORL lines also aligned with those reported for OSCC. By focusing on those gene
      expression signatures that are predictive of chemotherapeutic response, we
      observed that the ORL lines broadly clustered into three groups (cell cycle,
      xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle
      genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell
      viability assay. Overall, our in-depth characterization of clinically annotated
      ORL lines provides new insight into the molecular alterations synonymous with
      OSCC, which can facilitate in the identification of biomarkers that can be used
      to guide diagnosis, prognosis, and treatment of OSCC. 

PMID- 27050153
TI  - Characterization of malignant ovarian mass on [18F]FDG PET/CT: using metabolic
      indices and degree of solidity.
AB  - BACKGROUND: The utility of [18F]FDG PET/CT for characterizing malignant ovarian
      mass has not been extensively studied. Here, we investigated various parameters
      that could be useful to differentiate malignant ovarian mass. METHODS: We
      enrolled 51 female patients (53.4+/-15.0 years), with 86 ovarian masses, who
      underwent pretreatment [18F]FDG PET/CT. Thirty six lesions were
      histopathologically confirmed with ovarian serous adenocarcinoma. Thirty one
      ovarian masses from gastric cancer and 19 masses from colorectal cancer were
      diagnosed by histopathological study or clinical follow up. Ovarian masses were
      evaluated by size, solidity, and metabolic indices. The degree of solidity was
      scored from 1 to 5 according to the portion of solid and cyst. Metabolic activity
      was scored to be either positive (>=liver) or negative (<liver). SUVmax
      (SUVovary) and the ratio of SUVmax of ovary to SUVmean of the liver (Ovary/L
      ratio) were performed. Age, bilaterality and level of CA 125 were also compared.
      In statistical analysis, categorical variables were analyzed using Pearson's chi
      square test, while continuous variables were evaluated either independent
      student's t-test or Mann-Whitney test. Receiver-operating-characteristic analysis
      was used to obtain optimal cutoff values. RESULTS: Serous adenocarcinoma had
      significantly higher score in all metabolic indices over metastasis. However,
      there were no differences in all metabolic indices in ovarian metastasis. In
      contrast, solidity was different between metastatic mass from gastric and
      colorectal cancer. Ovarian metastasis from gastric cancer was significantly solid
      compared with that from colorectal cancer. In comparison of all three masses,
      solidity and all metabolic indices were significantly different. Patients with
      serous adenocarcinoma were older and had higher CA-125 level. Between metastases
      from gastric and colorectal cancer, there were no differences in age,
      bilaterality and CA-125. CONCLUSIONS: Metabolic indices such as SUVovary and
      Ovary/L ratio could be useful to differentiate serous adenocarcinoma from
      metastasis. Furthermore, the degree of solidity could play a role in predicting
      the origin of metastasis.

PMID- 27050154
TI  - Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide
      Unfolding Enzymes.
AB  - Molecular chaperones control the cellular folding, assembly, unfolding,
      disassembly, translocation, activation, inactivation, disaggregation, and
      degradation of proteins. In 1989, groundbreaking experiments demonstrated that a
      purified chaperone can bind and prevent the aggregation of artificially unfolded
      polypeptides and use ATP to dissociate and convert them into native proteins. A
      decade later, other chaperones were shown to use ATP hydrolysis to unfold and
      solubilize stable protein aggregates, leading to their native refolding.
      Presently, the main conserved chaperone families Hsp70, Hsp104, Hsp90, Hsp60, and
      small heat-shock proteins (sHsps) apparently act as unfolding nanomachines
      capable of converting functional alternatively folded or toxic misfolded
      polypeptides into harmless protease-degradable or biologically active native
      proteins. Being unfoldases, the chaperones can proofread three-dimensional
      protein structures and thus control protein quality in the cell. Understanding
      the mechanisms of the cellular unfoldases is central to the design of new
      therapies against aging, degenerative protein conformational diseases, and
      specific cancers. 

PMID- 27050152
TI  - Quantification of Carbon Nanotubes in Environmental Matrices: Current
      Capabilities, Case Studies, and Future Prospects.
AB  - Carbon nanotubes (CNTs) have numerous exciting potential applications and some
      that have reached commercialization. As such, quantitative measurements of CNTs
      in key environmental matrices (water, soil, sediment, and biological tissues) are
      needed to address concerns about their potential environmental and human health
      risks and to inform application development. However, standard methods for CNT
      quantification are not yet available. We systematically and critically review
      each component of the current methods for CNT quantification including CNT
      extraction approaches, potential biases, limits of detection, and potential for
      standardization. This review reveals that many of the techniques with the lowest
      detection limits require uncommon equipment or expertise, and thus, they are not
      frequently accessible. Additionally, changes to the CNTs (e.g., agglomeration)
      after environmental release and matrix effects can cause biases for many of the
      techniques, and biasing factors vary among the techniques. Five case studies are
      provided to illustrate how to use this information to inform responses to real
      world scenarios such as monitoring potential CNT discharge into a river or
      ecotoxicity testing by a testing laboratory. Overall, substantial progress has
      been made in improving CNT quantification during the past ten years, but
      additional work is needed for standardization, development of extraction
      techniques from complex matrices, and multimethod comparisons of standard samples
      to reveal the comparability of techniques. 

PMID- 27050155
TI  - Photolysis quantum yield measurements in the near-UV; a critical analysis of 1-(2
      nitrophenyl)ethyl photochemistry.
AB  - The photolysis quantum yield, Qp, of 1-(2-nitrophenyl)ethyl phosphate (caged Pi)
      measured in the near-UV (342 nm peak with 60 nm half-bandwidth) is 0.53 and is
      based on results reported in 1978 (Biochemistry, 17, 1929-1935). This article
      amplifies methodology for determining that Qp in view of different recent
      estimates. Some general principles together with other examples relating to
      measurement of Qp values are discussed together with their relevance to
      biological research.

PMID- 27050156
TI  - Community views and perspectives on public engagement in health technology
      assessment decision making.
AB  - Objectives The aim of the present study was to describe community views and
      perspectives on public engagement processes in Australian health technology
      assessment (HTA) decision making. Methods Six focus groups were held in Sydney
      (NSW, Australia) as part of a broad program of work on public engagement and HTA.
      Eligible participants were aged >=18 years and spoke English. Participants were
      asked about their views and perspectives of public engagement in the HTA decision
      making process, with responses analysed using a public participation framework.
      Results Fifty-eight participants aged 19-71 years attended the focus groups.
      Responses from the public indicated that they wanted public engagement in HTA to
      include a diversity of individuals, be independent and transparent, involve
      individuals early in the process and ensure that public input is meaningful and
      useful to the process. This was consistent with the public participation
      framework. Perceived shortcomings of the current public engagement process were
      also identified, namely the lack of awareness of the HTA system in the general
      population and the need to acknowledge the role different groups of stakeholders
      or 'publics' can have in the process. Conclusions The public do see a role for
      themselves in the HTA decision-making process. This is distinct to the
      involvement of patients and carers. It is important that any future public
      engagement strategy in this field distinguishes between stakeholder groups and
      outline approaches that will involve members of the public in the decision-making
      process, especially if public expectations of involvement in healthcare decision
      making continue to increase. What is known about this topic? The views and
      perspectives of patients and consumers are important in the HTA decision-making
      process. There is a move to involve the broader community, particularly as
      decisions become increasingly complex and resources more scarce. What does this
      paper add? It not been known to what extent, or at what points, the community
      would like to be engaged with the HTA decision-making process. The present study
      adds to the evidence base on this topic by identifying features of engagement
      that may be important in determining the extent of wider public involvement. It
      is clear that the community expects the system to be transparent, for patients to
      be involved early in specific processes and the wider community to be able to
      contribute to the broader vision of the healthcare system. What are the
      implications for practitioners? A formalised strategy is needed to include the
      public voice into health technology decisions. With the current level of reform
      in the healthcare sector and the focus on creating a sustainable healthcare
      system, there is a real opportunity to implement an approach that not only
      informs patients and the community of the challenges, but includes and
      incorporates their views into these decisions. This will assist in developing and
      adapting policy that is relevant and meets the needs of the population.

PMID- 27050157
TI  - A biocatalytic approach to capuramycin analogues by exploiting a substrate
      permissive N-transacylase CapW.
AB  - Using the ATP-independent transacylase CapW required for the biosynthesis of
      capuramycin-type antibiotics, we developed a biocatalytic approach for the
      synthesis of 43 analogues via a one-step aminolysis reaction from a methyl ester
      precursor as an acyl donor and various nonnative amines as acyl acceptors.
      Further examination of the donor substrate scope for CapW revealed that this
      enzyme can also catalyze a direct transamidation reaction using the major
      capuramycin congener as a semisynthetic precursor. Biological activity tests
      revealed that a few of the new capuramycin analogues have significantly improved
      antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium
      tuberculosis H37Rv. Furthermore, most of the analogues are able to be covalently
      modified by the phosphotransferase CapP/Cpr17 involved in self resistance,
      providing critical insight for future studies regarding clinical development of
      the capuramycin antimycobacterial antibiotics. 

PMID- 27050158
TI  - Monitoring the Collapse of pH-Sensitive Liposomal Nanocarriers and Environmental
      pH Simultaneously: A Fluorescence-Based Approach.
AB  - Nowadays, the encapsulation of therapeutic compounds in so-called carrier systems
      is a very smart method to achieve protection as well as an improvement of their
      temporal and spatial distribution. After the successful transport to the point of
      care, the delivery has to be released under controlled conditions. To monitor the
      triggered release from the carrier, we investigated different fluorescent probes
      regarding their response to the pH-induced collapse of pH-sensitive liposomes
      (pHSLip), which occurs when the environmental pH falls below a critical value.
      Depending on the probe, the fluorescence decay time as well as fluorescence
      anisotropy can be used equally as key parameters for monitoring the collapse.
      Especially the application of a fluorescein labeled fatty acid (fPA) enabled the
      monitoring of the pHSLips collapse and the pH of its microenvironment
      simultaneously without interference. Varying the pH in the range of 3 < pH < 9,
      anisotropy data revealed the critical pH value at which the collapse of the
      pHSLips occurs. Complementary methods, e.g., fluorescence correlation
      spectroscopy and dynamic light scattering, supported the analysis based on the
      decay time and anisotropy. Additional experiments with varying incubation times
      yielded information on the kinetics of the liposomal collapse.

PMID- 27050159
TI  - Hand-arm vibration disorder among grass-cutter workers in Malaysia.
AB  - INTRODUCTION: Prolonged exposure to hand-transmitted vibration from grass-cutting
      machines has been associated with increasing occurrences of symptoms and signs of
      occupational diseases related to hand-arm vibration syndrome (HAVS). METHODS: A
      cross-sectional study was carried out using an adopted HAVS questionnaire on hand
      arm vibration exposure and symptoms distributed to 168 male workers from the
      grass and turf maintenance industry who use hand-held grass-cutting machines as
      part of their work. The prevalence ratio and symptom correlation to HAVS between
      high and low-moderate exposure risk groups were evaluated. RESULTS: There were
      positive HAVS symptoms relationships between the low-moderate exposure group and
      the high exposure group among hand-held grass-cutting workers. The prevalence
      ratio was considered high because there were indicators that fingers turned white
      and felt numb, 3.63, 95% CI [1.41, 9.39] and 4.24, 95% CI [2.18, 8.27],
      respectively. Less than 14.3% of workers stated that they were aware of the
      occupational hand-arm vibration, and it seemed to be related to the finger
      blanching and numbness. CONCLUSION: The results suggest that HAVS is under
      diagnosed in Malaysia, especially in the agricultural sectors. More information
      related to safety and health awareness programmes for HAVS exposure is required
      among hand-held grass-cutting workers.

PMID- 27050160
TI  - Competing effect of spin-orbit torque terms on perpendicular magnetization
      switching in structures with multiple inversion asymmetries.
AB  - Current-induced spin-orbit torques (SOTs) in structurally asymmetric multilayers
      have been used to efficiently manipulate magnetization. In a structure with
      vertical symmetry breaking, a damping-like SOT can deterministically switch a
      perpendicular magnet, provided an in-plane magnetic field is applied. Recently,
      it has been further demonstrated that the in-plane magnetic field can be
      eliminated by introducing a new type of perpendicular field-like SOT via
      incorporating a lateral structural asymmetry into the device. Typically, however,
      when a current is applied to such devices with combined vertical and lateral
      asymmetries, both the perpendicular field-like torque and the damping-like torque
      coexist, hence jointly affecting the magnetization switching behavior. Here, we
      study perpendicular magnetization switching driven by the combination of the
      perpendicular field-like and the damping-like SOTs, which exhibits deterministic
      switching mediated through domain wall propagation. It is demonstrated that the
      role of the damping-like SOT in the deterministic switching is highly dependent
      on the magnetization direction in the domain wall. By contrast, the perpendicular
      field-like SOT is solely determined by the relative orientation between the
      lateral structural asymmetry and the current direction, regardless of the
      magnetization direction in the domain wall. The experimental results further the
      understanding of SOTs-induced switching, with implications for spintronic
      devices. 

PMID- 27050161
TI  - Superconductivity below 20 K in heavily electron-doped surface layer of FeSe bulk
      crystal.
AB  - A superconducting transition temperature (Tc) as high as 100 K was recently
      discovered in one monolayer FeSe grown on SrTiO3. The discovery ignited efforts
      to identify the mechanism for the markedly enhanced Tc from its bulk value of 8
      K. There are two main views about the origin of the Tc enhancement: interfacial
      effects and/or excess electrons with strong electron correlation. Here, we report
      the observation of superconductivity below 20 K in surface electron-doped bulk
      FeSe. The doped surface layer possesses all the key spectroscopic aspects of the
      monolayer FeSe on SrTiO3. Without interfacial effects, the surface layer state
      has a moderate Tc of 20 K with a smaller gap opening of 4.2 meV. Our results show
      that excess electrons with strong correlation cannot induce the maximum Tc, which
      in turn reveals the need for interfacial effects to achieve the highest Tc in one
      monolayer FeSe on SrTiO3. 

PMID- 27050162
TI  - Reversal of fluconazole resistance induced by a synergistic effect with Acca
      sellowiana in Candida glabrata strains.
AB  - CONTEXT: The increased incidence of non-albicans Candida (NAC) resistant to
      fluconazole (FLZ) makes it necessary to use new therapeutic alternatives. Acca
      sellowiana (O.berg) Burret (Myrtaceae) is a guava with several proven biological
      activities. The interaction with fluconazole can be a feasible alternative to
      overcome this resistance. OBJECTIVE: This study evaluates the in vitro antifungal
      activity of fractions obtained from the lyophilized aqueous extract of the leaves
      of A. sellowiana against resistant strains of NAC. MATERIALS AND METHODS: The
      antifungal activity of the fractions was evaluated at 500 MUg/mL by microdilution
      method. Checkerboard assay was performed to determine the effect of the
      combination of the F2 fraction and antifungal at concentrations: MIC/4, MIC/2,
      MIC, MIC * 2 and MIC * 4. RESULTS: Candida glabrata showed the lowest MIC values
      (500-3.90 MUg/mL) and the F2 active fraction was the most effective. The
      association of F2 with FLZ showed a strong synergistic effect (FICI <= 0.5)
      against 100% of C. glabrata resistant isolates. Moreover, the F2 active fraction
      has demonstrated that probably acts in the cell wall of these yeasts. There was
      no observed acute dermal toxicity of lyophilized aqueous extract of leaves of A.
      sellowiana on pig ear skin cells. DISCUSSION AND CONCLUSION: The interaction
      between substances present in the F2 active fraction is possibly responsible for
      the antifungal activity presented by this fraction. This study is unprecedented
      and suggests that the combination of F2 active fraction and FLZ might be used as
      an alternative treatment for mucocutaneus infections caused by C. glabrata
      resistant.

PMID- 27050163
TI  - Knockdown of Carboxypeptidase A6 in Zebrafish Larvae Reduces Response to Seizure
      Inducing Drugs and Causes Changes in the Level of mRNAs Encoding Signaling
      Molecules.
AB  - Carboxypeptidase A6 (CPA6) is an extracellular matrix metallocarboxypeptidase
      that modulates peptide and protein function by removal of hydrophobic C-terminal
      amino acids. Mutations in the human CPA6 gene that reduce enzymatic activity in
      the extracellular matrix are associated with febrile seizures, temporal lobe
      epilepsy, and juvenile myoclonic epilepsy. The characterization of these human
      mutations suggests a dominant mode of inheritance by haploinsufficiency through
      loss of function mutations, however the total number of humans with pathologic
      mutations in CPA6 identified to date remains small. To better understand the
      relationship between CPA6 and seizures we investigated the effects of morpholino
      knockdown of cpa6 mRNA in zebrafish (Danio rerio) larvae. Knockdown of cpa6 mRNA
      resulted in resistance to the effect of seizure-inducing drugs pentylenetetrazole
      and pilocarpine on swimming behaviors. Knockdown of cpa6 mRNA also reduced the
      levels of mRNAs encoding neuropeptide precursors (bdnf, npy, chga, pcsk1nl, tac1,
      nts, edn1), a neuropeptide processing enzyme (cpe), transcription factor (c-fos),
      and molecules implicated in glutamatergic signaling (grin1a and slc1a2b).
      Treatment of zebrafish embryos with 60 mM pilocarpine for 1 hour led to
      reductions in levels of many of the same mRNAs when measured 1 day after
      pilocarpine exposure, except for c-fos which was elevated 1 day after pilocarpine
      treatment. Pilocarpine treatment, like cpa6 knockdown, led to a reduced
      sensitivity to pentylenetetrazole when tested 1 day after pilocarpine treatment.
      Taken together, these results add to mounting evidence that peptidergic systems
      participate in the biological effects of seizure-inducing drugs, and are the
      first in vivo demonstration of the molecular and behavioral consequences of cpa6
      insufficiency. 

PMID- 27050164
TI  - Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor
      for Esophageal Squamous Cell Carcinoma.
AB  - Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine
      (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5
      carboxylcytosine, which result in genomic DNA demethylation. It was reported that
      5-hmC levels were decreased in a variety of cancers and could be regarded as an
      epigenetic hallmark of cancer. In the present study, 5-hmC levels were detected
      by immunohistochemistry (IHC) in 173 esophageal squamous cell carcinoma (ESCC)
      tissues and 91 corresponding adjacent non-tumor tissues; DNA dot blot assays were
      used to detect the 5-hmC level in another 50 pairs of ESCC tissues and adjacent
      non-tumor tissues. In addition, the mRNA level of TET1, TET2 and TET3 in these 50
      pairs of ESCC tissues was detected by real-time PCR. The IHC and DNA dot blot
      results showed that 5-hmC levels were significantly lower in ESCC tissues
      compared with corresponding adjacent non-tumor tissues (P = 0.029). TET2 and TET3
      expression was also significantly decreased in tumor tissues compared with paired
      non-tumor tissues (TET2, P < 0.0001; TET3, P = 0.009), and the decrease in 5-hmC
      was significantly associated with the downregulation of TET2 expression (r =
      0.405, P = 0.004). Moreover, the loss of 5-hmC in ESCC tissues was significantly
      associated with poor overall survival among patients with ESCC (P = 0.043);
      multivariate Cox regression analysis showed that the loss of 5-hmC in ESCC
      tissues was an independent unfavorable prognostic indicator for patients with
      ESCC (HR = 1.569, P = 0.029). In conclusion, 5-hmC levels were decreased in ESCC
      tissues, and the loss of 5-hmC in tumor tissues was an independent unfavorable
      prognostic factor for patients with ESCC. 

PMID- 27050166
TI  - Neurocognitive deficits in children and adolescents following maltreatment:
      Neurodevelopmental consequences and neuropsychological implications of traumatic
      stress.
AB  - Childhood maltreatment is a significant risk factor for a host of psychiatric,
      developmental, medical, and neurocognitive conditions, often resulting in
      debilitating and long-term consequences. However, there is no available
      neuropsychological resource reviewing the literature on the associated
      neurocognitive deficits in children and adolescents. This review comprehensively
      examines the 23 prior studies that evaluated the intellectual, language, visual
      spatial, memory, motor, and/or attention/executive functions in children and
      adolescents following an experience of childhood abuse and/or neglect.
      Neurocognitive impairments were frequently reported. Impairments in executive
      functions were the most frequent and severe reported impairments, although
      intelligence, language, visual-spatial skills, and memory are also at serious
      risk for compromised development following maltreatment. However, specific
      factors such as abuse/neglect duration, severity, type, and timing during
      development were all associated with neurocognition. This indicates that these
      factors are of greater importance than just the presence of abuse/neglect in
      identifying risk for neurocognitive compromise. Such neurocognitive deficits
      appear to be a consequence to the known neurobiological and brain development
      abnormalities of this population, suggesting traumatic stress can be a potential
      cause of neurodevelopmental disorders. These findings have critical implications
      for the clinical practice and research involving children following childhood
      maltreatment and other types of traumatic stress.

PMID- 27050168
TI  - Effects of Physical Practice and Imagery Practice on Bilateral Transfer in
      Learning a Sequential Tapping Task.
AB  - Recent research on bilateral transfer suggests that imagery training can
      facilitate the transfer of motor skill from a trained limb to that of an
      untrained limb above and beyond that of physical practice. To further explore
      this effect, the present study examined the influence of practice duration and
      task difficulty on the extent to which imagery training and physical training
      influences bilateral transfer of a sequential key pressing task. In experiment 1,
      participants trained on the key pressing task using their non-dominant arm under
      one of three conditions (physical practice, imagery practice, and no practice).
      In a subsequent bilateral transfer test, participants performed the sequential
      task using their untrained dominant arm in either an original order or mirror
      ordered sequence. In experiment 2, the same procedures were followed as in
      experiment 1 except that participants trained with their dominant arm and
      performed the bilateral transfer task with their non-dominant arm. Results
      indicated that with extended practice beyond what has been employed in previous
      studies, physical practice is more effective at facilitating bilateral transfer
      compared to training with imagery. Interestingly, significant bilateral transfer
      was only observed for transfer from the non-dominant to the dominant arm with no
      differences observed between performing the task in an original or mirror ordered
      sequence. Overall, these findings suggest that imagery training may benefit
      bilateral transfer primarily at the initial stages of learning, but with extended
      training, physical practice leads to larger influences on transfer. 

PMID- 27050169
TI  - Exploring Health Literacy in Medical University Students of Chongqing, China: A
      Cross-Sectional Study.
AB  - Health literacy is important in public health and healthcare, particularly in
      effective communication between patients and health professionals. Although most
      medical students will eventually work as health professionals after graduation,
      research on health literacy of medical students is scarce. This study aimed to
      assess the health literacy level of medical students in Chongqing, China, and its
      influencing factors. A cross-sectional study was conducted and 1,275 participants
      (250 males and 1,022 females) who majored in five different disciplines were
      involved. The Health Literacy Questionnaire was used as the survey tool. The
      junior students obtained the highest scores, whereas the freshman students had
      the lowest scores on each scale. The average score of males was higher than that
      of females except in "feeling understood and supported by healthcare providers,"
      and the average score of students who reside in urban areas was higher than that
      of students in rural areas. Moreover, the average score of engineering students
      was higher than that of medical or health sciences students. Multiple linear
      regression models (Radj2 = 0.435, P = 0.000) showed that the grade, socioeconomic
      status, and parent's highest level of education were positively correlated with
      health literacy. In conclusion, the health literacy levels of the medical
      students are insufficient and need improvement. 

PMID- 27050167
TI  - Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle
      Using Dogs with Spontaneously Occurring Tumors as a Model.
AB  - BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of
      cancer but toxicity on normal tissues often limits patient tolerance and often
      causes long-term adverse effects. The objective of this study was to assist in
      the preclinical development of using modified, non-living bacterially-derived
      minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth
      factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the
      safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated
      EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17
      companion dogs; a comparative oncology model of human brain cancers.
      METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via
      intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution
      was assessed using single-photon emission computed tomography (SPECT) and
      magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI,
      and blood samples were subject to toxicology (hematology, biochemistry) and
      inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly
      localized to the core of brain tumors. Complete resolution or marked tumor
      regression (>90% reduction in tumor volume) were observed in 23.53% of the
      cohort, with lasting anti-tumor responses characterized by remission in three
      dogs for more than two years. The median overall survival was 264 days (range 49
      to 973). No adverse clinical, hematological or biochemical effects were observed
      with repeated administration of EGFRminicellsDox (30 to 98 doses administered in
      10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with
      doxorubicin were safely administered to dogs with late stage brain cancer and
      clinical activity was observed. These findings demonstrate the strong potential
      for clinical applications of targeted, doxorubicin-loaded minicells for the
      effective treatment of patients with brain cancer. On this basis, we have
      designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells
      for effective treatment of human patients with recurrent glioblastoma.

PMID- 27050170
TI  - Influence of beam incidence and irradiation parameters on stray neutron doses to
      healthy organs of pediatric patients treated for an intracranial tumor with
      passive scattering proton therapy.
AB  - PURPOSE: In scattering proton therapy, the beam incidence, i.e. the patient's
      orientation with respect to the beam axis, can significantly influence stray
      neutron doses although it is almost not documented in the literature. METHODS:
      MCNPX calculations were carried out to estimate stray neutron doses to 25 healthy
      organs of a 10-year-old female phantom treated for an intracranial tumor. Two
      beam incidences were considered in this article, namely a superior (SUP) field
      and a right lateral (RLAT) field. For both fields, a parametric study was
      performed varying proton beam energy, modulation width, collimator aperture and
      thickness, compensator thickness and air gap size. RESULTS: Using a standard beam
      line configuration for a craniopharyngioma treatment, neutron absorbed doses per
      therapeutic dose of 63MUGyGy(-1) and 149MUGyGy(-1) were found at the heart for
      the SUP and the RLAT fields, respectively. This dose discrepancy was explained by
      the different patient's orientations leading to changes in the distance between
      organs and the final collimator where external neutrons are mainly produced.
      Moreover, investigations on neutron spectral fluence at the heart showed that the
      number of neutrons was 2.5times higher for the RLAT field compared against the
      SUP field. Finally, the influence of some irradiation parameters on neutron doses
      was found to be different according to the beam incidence. CONCLUSION: Beam
      incidence was thus found to induce large variations in stray neutron doses,
      proving that this parameter could be optimized to enhance the radiation
      protection of the patient.

PMID- 27050171
TI  - Advanced optimization methods for whole pelvic and local prostate external beam
      therapy.
AB  - PURPOSE: Radiation treatment planning inherently involves multiple conflicting
      planning goals, which makes it a suitable application for multicriteria
      optimization (MCO). This study investigates a MCO algorithm for VMAT planning
      (VMAT-MCO) for prostate cancer treatments including pelvic lymph nodes and uses
      standard inverse VMAT optimization (sVMAT) and Tomotherapy planning as
      benchmarks. METHODS: For each of ten prostate cancer patients, a two stage plan
      was generated, consisting of a stage 1 plan delivering 22Gy to the prostate, and
      a stage 2 plan delivering 50.4Gy to the lymph nodes and 56Gy to the prostate with
      a simultaneous integrated boost. The single plans were generated by three
      planning techniques (VMAT-MCO, sVMAT, Tomotherapy) and subsequently compared with
      respect to plan quality and planning time efficiency. RESULTS: Plan quality was
      similar for all techniques, but sVMAT showed slightly better rectum (on average
      Dmean -7%) and bowel sparing (Dmean -17%) compared to VMAT-MCO in the whole
      pelvic treatments. Tomotherapy plans exhibited higher bladder dose (Dmean +42%)
      in stage 1 and lower rectum dose (Dmean -6%) in stage 2 than VMAT-MCO. Compared
      to manual planning, the planning time with MCO was reduced up to 12 and 38min for
      stage 1 and 2 plans, respectively. CONCLUSION: MCO can generate highly conformal
      prostate VMAT plans with minimal workload in the settings of prostate-only
      treatments and prostate plus lymph nodes irradiation. In the whole pelvic plan
      manual VMAT optimization led to slightly improved OAR sparing over VMAT-MCO,
      whereas for the primary prostate treatment plan quality was equal.

PMID- 27050172
TI  - Multicenter evaluation of a synthetic single-crystal diamond detector for
      CyberKnife small field size output factors.
AB  - PURPOSE: The aim of the present work was to evaluate small field size output
      factors (OFs) using the latest diamond detector commercially available, PTW-60019
      microDiamond, over different CyberKnife systems. OFs were measured also by
      silicon detectors routinely used by each center, considered as reference.
      METHODS: Five Italian CyberKnife centers performed OFs measurements for field
      sizes ranging from 5 to 60mm, defined by fixed circular collimators (5 centers)
      and by Iris(TM) variable aperture collimator (4 centers). Setup conditions were:
      80cm source to detector distance, and 1.5cm depth in water. To speed up
      measurements two diamond detectors were used and their equivalence was evaluated.
      MonteCarlo (MC) correction factors for silicon detectors were used for comparing
      the OF measurements. RESULTS: Considering OFs values averaged over all centers,
      diamond data resulted lower than uncorrected silicon diode ones. The agreement
      between diamond and MC corrected silicon values was within 0.6% for all fixed
      circular collimators. Relative differences between microDiamond and MC corrected
      silicon diodes data for Iris(TM) collimator were lower than 1.0% for all
      apertures in the totality of centers. The two microDiamond detectors showed
      similar characteristics, in agreement with the technical specifications.
      CONCLUSIONS: Excellent agreement between microDiamond and MC corrected silicon
      diode detectors OFs was obtained for both collimation systems fixed cones and
      Iris(TM), demonstrating the microDiamond could be a suitable detector for
      CyberKnife commissioning and routine checks. These results obtained in five
      centers suggest that for CyberKnife systems microDiamond can be used without
      corrections even at the smallest field size.

PMID- 27050173
TI  - A Retrospective Comparative Study of Concomitant Chemoradiotherapy followed by
      Adjuvant Temozolomide Versus Radiotherapy Alone In Newly Diagnosed Glioblastoma
      Multiforme - An Experience at Radium Institute, Patna Medical College and
      Hospital, India.
AB  - INTRODUCTION: Glioblastoma Multiforme (WHO grade IV glioma) still remains a
      dreadful diagnosis in oncology with the median survival ranging between 12 to 17
      months, despite the recent advances in its management. It is the most common
      malignant primary tumour in adults(13). The standard of care is Maximal Safe
      Resection followed by Concomitant ChemoRadiotherapy. METHODS: During the period
      2006 to 2010 at Radium Institute, Patna Medical College and Hospital (PMCH) in
      India, a study was conducted on 37 newly diagnosed GBM cases in which the control
      arm (c-arm) received Conventional Radiotherapy (60Gy/30#) only whereas the study
      arm (s-arm) received Concomitant Chemoradiotherapy followed by Adjuvant
      Temozolomide. RESULTS: The median survival was 15.4 months in the s-arm as
      compared to 12.4 months in the c-arm. The OS showed a significant improvement
      with p-value of 0.05 and PFS also showed a benefit with a p-value of 0.005.
      CONCLUSION: The results were encouraging with improvement in OS as well as PFS in
      the s-arm and were at par with the other similar studies conducted in different
      parts of the world.

PMID- 27050174
TI  - EGFR and HER-2/neu Expression in Gallbladder Carcinoma: An Institutional
      Experience.
AB  - BACKGROUND: Gallbladder cancer (GBC) is the most common malignancy of the biliary
      tract in India. Despite the recent advancement in the understanding of the cancer
      biology, the disease still remains a therapeutic challenge with poor prognosis
      and low survival. Surgery is the primary modality of treatment and rest of the
      modalities are basically adjuvant in nature. This study was performed to evaluate
      the epidermal growth factor receptor (EGFR) and human epidermal growth factor
      receptor-2 HER-2/neu) expression in GBC. METHODS: The present study was
      prospective and done in tertiary super-specialty institute of northern India.
      This was a pilot study, and at the time of completion, 29 samples were found
      suitable which were later submitted for EGFR and HER-2/neu evaluation. The sample
      includes both cases of GBC (n=18) and cholecystitis (n=11) as control. (Table 1)
      After performing necessary processing, slides were incubated with primary
      antibody (EGFR) ready to use (RTU) BioGenex, India and HER-2/neu dilution 1:600,
      Dakopatts (Denmark). Then slides were incubated with secondary antibody (Real
      Envision Detection Kit, Dakopatts, Denmark). Finally in mounted slides, cell
      membrane staining was used to assess positivity for EGFR and HER-2/neu. RESULTS:
      EGFR was positive in 21/29 (72.41%) overall, out of which 14/18 (77.78%) positive
      in cases and 7/11 (63.64%) positive in control. (Table 1, 3)(Figure 2). For HER
      2/neu, it was positive in 21/29 (72.41%) overall, just like in EGFR mentioned
      above, but positive 12/18 (66.67%) in cases and 9/11 (81.82%) in control
      respectively. CONCLUSION: Despite the efforts by many investigators, GBC
      continues to represent a major challenge in oncology. Surgical resection remains
      the only curative treatment for this disease. The roles of radiation,
      chemoradiation, and chemotherapy in neoadjuvant and adjuvant settings remained to
      be defined in prospective studies. With further studies based on molecular
      understanding and developing new targeted therapies, we will be in better
      position to manage GBC and increase the survival rate.

PMID- 27050175
TI  - Potential Co-Relation Between Chronic Periodontitis And Cancer - An Emerging
      Concept.
AB  - Periodontal disease caused chiefly by bacteria is characterized by inflammation,
      bacteremia, and a strong immune response. It is based on evidence that a
      continuous long-term exposure to oral bacteremia and bacterial toxins induces
      inflammatory immune response after immune evasion releases growth factors such as
      FGF, EGF, TGF-Beta, free radicals such as ROS and NOS, cytokines such as TNFAlfa,
      IL-1 Beta, IL-6; and matrix metalloproteinase such as MMP-9. Immature myeloid
      cells such as macrophages, dendritic cells and granulocytes involved in chronic
      inflammation and tumor progression through immunosuppressive activity against
      innate and adaptive immunity by factors such as iNOS, Arginase1 and ROS, activate
      major transcriptional factors such as NF-KB and STAT3 that could contribute to
      genetic instability, uncontrolled cell proliferation, angiogenesis, resistance to
      apoptosis, epithelial to mesenchymal transition, immunosuppression, invasion and
      metastasis. This study is a product of research and analysis on the role of
      chronic inflammatory mediators of chronic periodontitis in progression to cancer.

PMID- 27050176
TI  - Primary Parotid Lymphoma From A Regional Cancer Center in South India.
AB  - Primary parotid lymphoma (PPL) is an unusual entity and there is limited data in
      Indian population. Hence we undertook this retrospective observational study of
      primary parotid lymphoma at our Center in Southern India. This study includes 7
      consecutive cases diagnosed as PPL by tissue biopsy/superficial/deep
      parotidectomy confirmed by immunohistochemistry between January 2007 and December
      2012. RESULTS: Median age was 54 years (range 29- 78 years), and it was more
      common in males. According to Ann Arbor stage, Advanced stage (stage III and IV)
      was seen in 2 (28.57%). According to the International Prognostic Index (IPI),
      most (6) were low risk (85.7%). Overall survival ranged from 1-45 months with
      median OS of 18 months. To conclude, PPL presents more often in early stage and
      low IPI score. Surgery +/- chemoimmunotherapy with radiotherapy to the parotid is
      the standard treatment at present.

PMID- 27050177
TI  - Honey on oral mucositis: A Randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVE: The main stream of management of head and neck cancer
      is by radiotherapy and surgery. During radiation therapy in head and neck
      cancers, oral cavity is directly exposed to high dose radiation which leads to
      several side effects - oral mucositis being the most distressing one. This study
      was intended to assess the effects of applying honey on oral mucositis during
      radiation therapy. MATERIAL AND METHODS: The research design used in this study
      was Randomized Control Trial with single blinding method in the Radiotherapy Unit
      of Regional Cancer Centre (RCC), at JIPMER. The study population included a total
      of 28 patients. Participants in experimental group were given 15ml natural honey
      for applying on oral mucosa and in control group 15ml plain water were given.
      Assessment of oral mucosa was done after every 5 doses of radiation therapy using
      RTOG scale and severity of oral mucositis was assessed. RESULTS: There was a
      statistically significant difference in degree of oral mucositis between the
      experimental and control group in week 4, 5 and 6 (p<0.01). During the whole
      course of study, 9 (64.28 percent) participants in control group developed grade
      III oral mucositis while only one participant (7.14%) in experimental group
      developed grade III oral mucositis. CONCLUSION: The study concluded that applying
      natural honey on oral mucositis was effective among head and neck cancers
      patients receiving external beam radiation therapy.

PMID- 27050178
TI  - Clinical Characteristics and prognostic analysis of Triple-negative Breast
      Cancer: Single institute experience.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is a poor prognostic subset of
      breast cancer that lacks the benefit of specific targeted therapy. MATERIALS AND
      METHODS: A prospective study of the clinical profile of triple negative breast
      cancer cases at a tertiary referral centre. The duration of the study period was
      26 months and the median follow up period was ten months. A total of 111 invasive
      breast cancer patients were evaluated from 1st August 2009 to 31st October 2011.
      We examined TNBC patients with respect to clinicopathological parameters,
      adjuvant chemotherapy regimens and relapse free survival. RESULTS: In our study,
      patients were young (median age at presentation, 47yrs), premenopausal (54%),
      tumour size was discordant with lymph node positivity, the histology was
      predominantly intraductal carcinoma (90%), histological grade higher than two
      (90%). Relapses were early and preferential visceral (32%) and CNS metastasises
      (11.7%). 91% of patients were eligible for adjuvant therapy but only 80% of the
      patients could complete full course of adjuvant chemotherapy. Anthracycline-based
      regimens (43%), sequential anthracycline and taxane-based regimen (24%) and other
      regimes like CMF (13%) were used as adjuvant chemotherapy in eligible TNBC
      patients. Median relapse free survival in patients following adjuvant
      chemotherapy was around 10 months at last follow-up. CONCLUSIONS: Patients with
      TNBC have aggressive clinicopathological characteristics with early and higher
      rate of disease relapse and therefore derive inadequate benefit from current
      adjuvant chemotherapy. So, new treatment strategies in adjuvant chemotherapy for
      TNBC are needed.

PMID- 27050179
TI  - Histopathological pattern of thyroid diseases among patients in Hadhramout-Yemen.
AB  - OBJECTIVE: To determine the histopathological pattern of thyroid diseases among
      patients in Hadhramout Province, Yemen Methods: A descriptive retrospective study
      was conducted at Ibn Sina Central Teaching Hospital, in Mukalla city, Hadhramout,
      Yemen between January 2007 and December 2012. Eight hundred and seventeen
      patients with thyropathy were included in this study diagnosed histologically by
      experienced pathologists using fine needle aspiration cytology. This was followed
      up by postoperative pathological thyroid specimen study. The patients in the
      study were treated medically and surgically by authors. RESULTS: 817 patients
      with thyropathy were included in the study. There were 716 (87.6%) females and
      101 (12.4%) males, with a female to male ratio of 7:1. The age of the patients
      ranged from 5 to 80 years, with a mean age of 37.7+/-12.2 years. Median age was
      35. More than half of the patients aged between 21-40 years. The majority of the
      thyroid lesions were non neoplastic = 703 (86%). The most common lesion was
      simple colloid goiter = 578 (82%) followed by thyroid Hashimoto = 75 (10.7%). The
      minority were granulomatous (subacute) thyroiditis, hyperplastic nodule and
      thyroglossal cyst, 5 (0.7%), 6 (0.9%), 8 (1.1%) respectively. 114 (14%) patients
      have neoplastic lesions. 61 (7.5%) patients have benign adenoma, 2 (1.75%)
      patients have Hurthel cell adenoma. 43 (5.3%) patients have papillary carcinoma
      while 3 (2.63%) patients have anaplastic carcinoma. The less common malignant
      neoplastic thyroid lesions were primary lymphoma, follicular and medullary
      carcinoma, and mucoepidermoid carcinoma, 2 (1.75%), 1 (0.9%), 1 (0.9%), and 1
      (0.9%) respectively. CONCLUSION: The most common non-neoplastic thyroid disorder
      reported in this study is a simple colloid goiter. Adenoma was found to be the
      most common benign tumor while papillary carcinoma was found to be the most
      common malignant one. Most cancerous lesions were found within the age groups in
      the third and the fourth decade, mostly females.

PMID- 27050180
TI  - Exploring the Clinicopathological Parameters Affecting the Outcome in Egyptian
      Patients with Multiple Myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is a plasma-cell neoplasm in which the
      interplay of several clinical, pathological and genetic parameters affects the
      patient's prognosis and response to treatment and survival. AIM: The aim of this
      study was to evaluate the different clinicopathological parameters of MM patients
      in correlation with response to therapy, progressionfree survival (PFS) and
      overall survival (OS). METHODS: This retrospective study was performed on 60 MM
      patients diagnosed at NCI, Cairo University from January 2005 to December 2008.
      The patients were evaluated for different clinicopathological parameters which
      were correlated to their response to treatment, OS and PFS. RESULTS: Sixty
      patients were followed up for a median period of 21 months wherein about 90%
      received 1st line treatment: 34 VAD, 17 MP and 3 dexamethasone. Six patients
      (10%) were referred for BSC. CR was achieved by 15%, 11.7% achieved good PR, 6.7%
      achieved PR, 22.1% have stable disease, 35% experienced disease progression. ECOG
      PS-I patients have 39 months median survival compared to 12 months for patients
      with PS ECOG-II (P 0.005). Patients with multiple skeletal lesions (>=3) have
      median OS of 19 months (P 0.03). Patients who presented with plasmacytoma have
      better OS than those without (38 months versus 14 months) (P<0.05). Patients <60
      years old have a better median OS compared to patients <60 years (37 months
      versus 12 months) (P 0.001). OS was 39 months in female patients versus 14 months
      in male patients (P0.025). Median OS was 9 months for patients with comorbidities
      versus 27 months for those without (P0.01), 39 months for patients with non
      detected paraproteinuria versus 18 months for those with paraproteinuria (P
      0.045), 18 months for stage II disease versus 12 months for stage III disease
      (P0.001), 12 months for patients with elevated serum LDH versus 39 months for
      those with normal levels (P 0.001), 27 months for patients with normal serum
      creatinine level versus 13 months for those with elevated levels (>1.4 mg/dl) (P
      0.005), 27 months for patients with normal serum calcium levels versus 10 months
      for those with hypercalcemia (P 0.03). CONCLUSION: Besides FISH-guided molecular
      cytogenetic classification of myeloma abnormality, a specific risk-stratification
      model based upon the patient's age, sex, performance status, lytic bone lesions,
      plasma cells labeling index, serum creatinine, calcium, LDH, B2M and paraproteins
      in serum and urine, can depict the response to treatment, OS and PFS of patients
      with MM.

PMID- 27050181
TI  - Multidetector CT (MDCT) Findings Of Primary Hepatic Lymphoma.
AB  - OBJECTIVE: The aim of this study was to describe the triphasic multidetector CT
      (MDCT) finding of primary hepatic lymphoma (PHL). MATERIALS AND METHODS: This
      retrospective study included eighteen patients. Each patient presented with
      primary hepatobiliary lymphoma without associated lymphadenopathy or other
      visceral involvement. Triphasic CT scanning was performed on one of two systems
      (64 MD CT) in 12 patients and (6 MDCT) in 6 patients. All eighteen patients
      underwent ultrasound percutaneous trucut liver biopsy using 18-gauge biopsy
      needle. Pathology was confirmed on all cases. RESULTS: Four of eighteen patients
      presented with a single focal lesion. Thirteen of eighteen patients presented
      with multiple well defined focal lesions. One patient presented with a diffuse
      hepatic involvement. On triphasic CT, three patients showed gradual progressive
      contrast enhancement. Lesions remained isodense to the liver on the arterial
      phase with mild enhancement in the portal phase and showed washout on the delayed
      phase in two patients. The remaining thirteen patients showed multiple hypodense
      non-enhancing lesions. CONCLUSIONS: PHL presents a wide spectrum of imaging
      findings on triphasic MDCT with no characteristic imaging pattern. MDCT can be
      used for detection of the lesion and biopsy is used for diagnosis. PHL should
      always be considered in the differential diagnosis of a liver focal lesion either
      single or multiple.

PMID- 27050182
TI  - Mobile Phone Use and the Risk of Parotid Gland Tumors: A Retrospective Case
      Control Study.
AB  - BACKGROUND: Mobile phones are integral part of the modern lifestyle. As they emit
      radio frequency electromagnetic field, their role in carcinogenesis needs to be
      ascertained. The goal of this study was to investigate the association between
      the use of cellular phones and the risk for parotid gland tumors. MATERIALS AND
      METHODS: A total of 26 patients diagnosed with parotid gland tumors and 61
      healthy controls were enrolled through a hospital-based retrospective case
      control study. The patients were referred and admitted to a tertiary hospital
      from January 1996 to March 2013. RESULTS: The Odds of exposure were 3.47 times
      higher among patients compared to their controls. 95% CI suggested that the true
      Odds Ratio (OR) at the population level could be somewhere between 1.3 and 9.23
      and so the observed OR was statistically significant at 5% level of significance.
      CONCLUSIONS: Overall, an association between the exposure of cellular phone use
      for more than 1 hour daily and parotid tumor was observed. This association
      should be interpreted with caution because of the relatively small sample size.

PMID- 27050183
TI  - Clinicopathological Spectrum Of Gall Bladder Cancer In Kashmir - An Institutional
      Study.
AB  - Gallbladder cancer is a highly aggressive malignancy that usually presents at an
      advanced incurable stage. It is the fifth most common gastro-intestinal tumor and
      leads to approximately 2800 deaths in United States annually. This was a
      retrospective study carried out in the Department of Pathology, Sher-i-Kashmir
      Institute of Medical Sciences, a 650-bed super speciality hospital in Kashmir
      valley. We reviewed the histopathological records of all the patients who were
      diagnosed as carcinoma gallbladder from Dec 2009-Dec 2013. Gross findings and
      histopathological findings were noted from the departmental archival material and
      clinical records of the patients including the clinical presentation, laboratory
      investigations, radiological investigations, pre-operative diagnosis and intra
      operative findings, were retrieved from the hospital records. We analyzed 57
      cases of carcinoma gallbladder for their clinicopathological features It included
      19 males and 37 females. In our study, adenocarcinomas accounted for 87.5% of
      total carcinomas. Incidentally, all but one patient where gall stones were found,
      adenocarcinomas were seen. We have 4 patients of squamous cell carcinoma. In our
      series we have a single case of small cell carcinoma which was positive for
      neuroendocrine markers. In our study, gall stones were seen only in 8 cases (14%)
      of the total cases. 

PMID- 27050184
TI  - Chronic Inflammation and Cancer: Paradigm on Tumor Progression, Metastasis and
      Therapeutic Intervention.
AB  - As early as the 19th century, inflammation has been perceived to have a link with
      cancer but this perception has waned through the passing of time. In recent years
      however a renewed interest on inflammation and cancer connection stemming from
      different lines of work has been evolved that leads to a generally-accepted
      paradigm. In the tumor microenvironment, smouldering inflammation contributes to
      the proliferation and survival of malignant cells, angiogenesis, metastasis,
      subversion of adaptive immunity, reduced response to hormones and
      chemotherapeutic agents. Thus, this review will try to unravel and explain
      molecular events, mediators and regulators linking inflammation to cancer. 

PMID- 27050185
TI  - International Mobile-Health Intervention on Physical Activity, Sitting, and
      Weight: The Stepathlon Cardiovascular Health Study.
AB  - BACKGROUND: Although proof-of-concept for mobile health (mHealth) life-style
      programs targeting physical inactivity and overweight/obesity has been
      established in randomized trials, the feasibility and effect of a globally
      distributed, large-scale, mass-participation mHealth implementation has not been
      investigated. OBJECTIVES: The purpose of this study was to determine the effect
      of Stepathlon, an international, low-cost, mass-participation mHealth
      intervention, on physical activity, sitting, and weight. METHODS: We
      prospectively collected cohort data from participants completing Stepathlon, an
      annual 100-day global event in 2012, 2013, and 2014. Participants were organized
      in worksite-based teams, issued pedometers, and encouraged to increase daily
      steps and physical activity as part of the team-based race. The program was
      conducted via an interactive multiplatform application available on mobile
      devices and the Internet. Analysis was performed according to a pre-specified
      plan. RESULTS: A total of 69,219 subjects participated (481 employers, 1,481
      cities, 64 countries, all populated continents, age 36 +/- 9 years, 23.9% female,
      8.0% high-income countries, and 92.0% lower-middle income countries). After
      Stepathlon completion, participants recorded improved step count (+3,519
      steps/day; 95% confidence interval [CI]: 3,484 to 3,553 steps/day; p < 0.0001),
      exercise days (+0.89 days; 95% CI: 0.87 to 0.92 days; p < 0.0001), sitting
      duration (-0.74 h; 95% CI: -0.78 to -0.71 h; p < 0.0001) and weight (-1.45 kg;
      95% CI: -1.53 to -1.38 kg; p < 0.0001). Improvements occurred in women and men,
      in all geographic regions, and in both high and lower-middle income countries,
      and the results were reproduced in 2012, 2013, and 2014 cohorts. Predictors of
      weight loss included step increase, sitting duration decrease, and increase in
      exercise days (all p < 0.0001). CONCLUSIONS: Distributed mHealth implementation
      of a low-cost life-style intervention is associated with short-term,
      reproducible, large-scale improvements in physical activity, sitting, and weight.
      (Effect of the Stepathlon Pedometer Program on Physical Activity, Weight and Well
      Being; ACTRN12615001310550).

PMID- 27050186
TI  - Interventions for Increasing Physical Activity: From "Ingenious Toys" to mHealth.

PMID- 27050187
TI  - 3-Year Outcomes in High-Risk Patients Who Underwent Surgical or Transcatheter
      Aortic Valve Replacement.
AB  - BACKGROUND: In patients with severe aortic stenosis at increased risk for
      surgery, self-expanding transcatheter aortic valve replacement (TAVR) is
      associated with improved 2-year survival compared with surgery. OBJECTIVES: This
      study sought to determine whether this clinical benefit was sustained over time.
      METHODS: Patients with severe aortic stenosis deemed at increased risk for
      surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open
      surgical valve replacement (SAVR). Three-year clinical and echocardiographic
      outcomes were obtained in those patients with an attempted procedure. RESULTS: A
      total of 797 patients underwent randomization at 45 U.S. centers; 750 patients
      underwent an attempted procedure. Three-year all-cause mortality or stroke was
      significantly lower in TAVR patients (37.3% vs. 46.7% in SAVR; p = 0.006).
      Adverse clinical outcome components were also reduced in TAVR patients compared
      with SAVR patients, including all-cause mortality (32.9% vs. 39.1%, respectively;
      p = 0.068), all stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major
      adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively;
      p = 0.025). At 3 years aortic valve hemodynamics were better with TAVR patients
      (mean aortic valve gradient 7.62 +/- 3.57 mm Hg vs. 11.40 +/- 6.81 mm Hg in SAVR;
      p < 0.001), although moderate or severe residual aortic regurgitation was higher
      in TAVR patients (6.8% vs. 0.0% in SAVR; p < 0.001). There was no clinical
      evidence of valve thrombosis in either group. CONCLUSIONS: Patients with severe
      aortic stenosis at increased risk for surgery had improved 3-year clinical
      outcomes after TAVR compared with surgery. Aortic valve hemodynamics were more
      favorable in TAVR patients without differences in structural valve deterioration.
      (Safety and Efficacy Study of the Medtronic CoreValve((r)) System in the
      Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk
      Subjects Who Need Aortic Valve Replacement; NCT01240902).

PMID- 27050188
TI  - Intravenous Beta-Blockers for Cardioprotection in STEMI: The Saga Continues.

PMID- 27050189
TI  - Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial
      Infarction Before Primary Percutaneous Coronary Intervention.
AB  - BACKGROUND: The impact of intravenous (IV) beta-blockers before primary
      percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes
      is not well established. OBJECTIVES: This study sought to conduct the first
      double-blind, placebo-controlled international multicenter study testing the
      effect of early IV beta-blockers before PPCI in a general ST-segment elevation
      myocardial infarction (STEMI) population. METHODS: STEMI patients presenting <12
      h from symptom onset in Killip class I to II without atrioventricular block were
      randomized 1:1 to IV metoprolol (2 * 5-mg bolus) or matched placebo before PPCI.
      Primary endpoint was myocardial infarct size as assessed by cardiac magnetic
      resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct
      size and incidence of ventricular arrhythmias. Safety endpoints included
      symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock. RESULTS:
      A total of 683 patients (mean age 62 +/- 12 years; 75% male) were randomized to
      metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients
      (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ
      between the metoprolol (15.3 +/- 11.0%) and placebo groups (14.9 +/- 11.5%; p =
      0.616). Peak and area under the creatine kinase curve did not differ between both
      groups. LV ejection fraction by CMR was 51.0 +/- 10.9% in the metoprolol group
      and 51.6 +/- 10.8% in the placebo group (p = 0.68). The incidence of malignant
      arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050).
      The incidence of adverse events was not different between groups. CONCLUSIONS: In
      a nonrestricted STEMI population, early intravenous metoprolol before PPCI was
      not associated with a reduction in infarct size. Metoprolol reduced the incidence
      of malignant arrhythmias in the acute phase and was not associated with an
      increase in adverse events. (Early-Beta blocker Administration before reperfusion
      primary PCI in patients with ST-elevation Myocardial Infarction [EARLY-BAMI];
      EudraCT no: 2010-023394-19).

PMID- 27050190
TI  - 3-Year Results of a TAVR Trial in High Surgical Risk Patients.

PMID- 27050191
TI  - Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia
      Genes in Patients With Severe Hypercholesterolemia.
AB  - BACKGROUND: Approximately 7% of American adults have severe hypercholesterolemia
      (untreated low-density lipoprotein [LDL] cholesterol >=190 mg/dl), which may be
      due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in
      FH mutation carriers may confer coronary artery disease (CAD) risk beyond that
      captured by a single LDL cholesterol measurement. OBJECTIVES: This study assessed
      the prevalence of an FH mutation among those with severe hypercholesterolemia and
      determined whether CAD risk varies according to mutation status beyond the
      observed LDL cholesterol level. METHODS: Three genes causative for FH (LDLR,
      APOB, and PCSK9) were sequenced in 26,025 participants from 7 case-control
      studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5
      prospective cohort studies (11,908 participants). FH mutations included loss-of
      function variants in LDLR, missense mutations in LDLR predicted to be damaging,
      and variants linked to FH in ClinVar, a clinical genetics database. RESULTS:
      Among 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%)
      had LDL cholesterol >=190 mg/dl; of these, only 24 (1.7%) carried an FH mutation.
      Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH
      mutation carriers than noncarriers. Compared with a reference group with LDL
      cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol >=190
      mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95%
      confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol >=190
      mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3;
      95% confidence interval: 10.7 to 53.2). In an analysis of participants with
      serial lipid measurements over many years, FH mutation carriers had higher
      cumulative exposure to LDL cholesterol than noncarriers. CONCLUSIONS: Among
      participants with LDL cholesterol >=190 mg/dl, gene sequencing identified an FH
      mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers
      had substantially increased risk for CAD.

PMID- 27050195
TI  - Duplex ultrasound surveillance after carotid artery endarterectomy.
AB  - OBJECTIVE: After carotid endarterectomy (CEA), patients have been regularly
      followed up by duplex ultrasound imaging. However, the evidence for long-term
      follow-up is not clear, especially if the results from an early duplex scan are
      normal. This study assessed and systematically reviewed the evidence base for
      long-term surveillance after CEA and a normal early scan. METHODS: Electronic
      databases were searched for studies assessing duplex surveillance after CEA in
      accordance with Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines. The primary outcome for this study was the incidence of
      restenosis after a normal early scan. The secondary outcome was the number of
      reinterventions after a normal early scan. RESULTS: The review included seven
      studies that reported 2317 procedures. Of those patients with a normal early
      scan, 2.8% (95% confidence interval, 0.7%-6%) developed a restenosis, and 0.4%
      (95% confidence interval, 0%-0.9%) underwent a reintervention for their
      restenosis during the follow-up period. CONCLUSIONS: This review confirms that
      routine postoperative duplex ultrasound surveillance after CEA is not necessary
      if the early duplex scan is normal.

PMID- 27050193
TI  - A Novel Prioritization Method in Identifying Recurrent Venous Thromboembolism
      Related Genes.
AB  - Identifying the genes involved in venous thromboembolism (VTE) recurrence is
      important not only for understanding the pathogenesis but also for discovering
      the therapeutic targets. We proposed a novel prioritization method called
      Function-Interaction-Pearson (FIP) by creating gene-disease similarity scores to
      prioritize candidate genes underling VTE. The scores were calculated by
      integrating and optimizing three types of resources including gene expression,
      gene ontology and protein-protein interaction. As a result, 124 out of top 200
      prioritized candidate genes had been confirmed in literature, among which there
      were 34 antithrombotic drug targets. Compared with two well-known gene
      prioritization tools Endeavour and ToppNet, FIP was shown to have better
      performance. The approach provides a valuable alternative for drug targets
      discovery and disease therapy. 

PMID- 27050192
TI  - The Aetiologies and Impact of Fever in Pregnant Inpatients in Vientiane, Laos.
AB  - INTRODUCTION: Laos has the highest maternal mortality ratio in mainland Southeast
      Asia and a high incidence of infectious diseases. Globally, malaria has been the
      pathogen most intensively investigated in relation to impact on pregnancy, but
      there has been relatively little research on the aetiology and impact of other
      diseases. We therefore aimed to determine the causes and impact of fever in
      pregnant women admitted to two central hospitals in Vientiane City, Lao PDR
      (Laos). MATERIALS AND METHODS: This hospital-based prospective study was
      conducted in Mahosot Hospital and the Mother and Child Hospital, Vientiane,
      between 2006 and 2010, with the aim to recruit 250 consenting pregnant women
      admitted with tympanic temperature >=37.5 degrees C. Primary outcome was the
      cause of fever and secondary outcomes were pregnancy outcomes. Specific
      investigations (culture, antigen, molecular and serological tests) were performed
      to investigate causes of fever. After discharge, all pregnant women were asked to
      return for review and convalescence serum on day 10-14 and were monitored until
      delivery. PRINCIPLE FINDINGS: 250 pregnant women were recruited to this study
      between February 2006 and November 2010. Fifty percent were pregnant for the
      first time. Their median (range) gestational age on admission was 24 (4-43)
      weeks. The median (range) tympanic admission temperature was 38.5 degrees C (37.5
      40.5 degrees C). Fifteen percent of patients stated that they had taken
      antibiotics before admission. Headache, myalgia, back pain and arthralgia were
      described by >60% of patients and 149 (60%) were given a laboratory diagnosis. Of
      those with confirmed diagnoses, 132 (53%) had a single disease and 17 (7%) had
      apparent mixed diseases. Among those who had a single disease, dengue fever was
      the most common diagnosis, followed by pyelonephritis, scrub typhus, murine
      typhus and typhoid. Patients were also diagnosed with tuberculosis, appendicitis,
      Staphylococcus aureus septicemia, leptospirosis, Japanese encephalitis virus
      infection and Plasmodium falciparum malaria. Severe consequences, including
      maternal death, miscarriage, stillbirth, low birth weight and preterm birth, were
      found among 28 (78%) mothers with dengue fever, rickettsioses and typhoid.
      CONCLUSION: Fevers other than malaria, such as dengue, pyelonephritis,
      rickettsioses and typhoid are common causes of fever during pregnancy in the
      Asian tropics. Further investigations of their impact in the community on
      maternal death, fetal loss, vertical transmission, low birth weight and preterm
      birth are needed.

PMID- 27050196
TI  - Early and intermediate results of endovascular treatment of symptomatic and
      asymptomatic visceral artery aneurysms.
AB  - OBJECTIVE: The treatment outcomes of symptomatic visceral artery aneurysms
      (SVAAs) have been sparsely characterized, with no clear comparisons between
      different treatment modalities. The purpose of this study was to review the
      outcomes of SVAAs and asymptomatic visceral artery aneurysms (ASVAAs) after
      endovascular treatment (ET). METHODS: The records of all patients with visceral
      artery aneurysms (VAAs) at our center from March 2004 to December 2014 were
      retrospectively reviewed. Patient demographics, aneurysm characteristics,
      management, perioperative and long-term outcomes, and complications were
      recorded. RESULTS: A total of 155 patients' records were reviewed; 106 patients
      (113 VAAs) were repaired with ET, including 27 symptomatic and 79 asymptomatic
      patients. The remaining 49 patients were treated with open surgery repair or
      conservative therapy. There was no significant difference of the diameters
      between SVAA and ASVAA (36.9 +/- 15.3 mm vs 33.6 +/- 36.1 mm, respectively; P =
      .746), and pseudoaneurysms were more common in the SVAA patients (13.8% vs 2.4%;
      P = .037). The most common presentation was abdominal pain. In the SVAA group,
      17.2% of patients presented with rupture. The immediate technical success rates
      of SVAA and ASVAA repairs were 96.3% and 97.5%, respectively. The 30-day
      mortality rate was 2.8% for all VAAs; however, this was significantly higher in
      the SVAA group (11.1%) than in the ASVAA group (0%; P = .015). The perioperative
      complication rate was not statistically different between the two groups (P =
      .553). The median duration of follow-up was 39.1 +/- 29.2 months (range, 1-112
      months). Overall mortality in all VAA patients was 6.6%, and the direct and
      indirect aneurysm-related mortality was 3.8%. There was a statistical difference
      in the overall survival rate between the SVAA and ASVAA groups at 3 years (85.2%
      vs 97.5%; P = .044). The reintervention rate was 3.8%, and this tended to be
      higher for SVAAs (11.1%) than for ASVAAs (1.3%; P = .050). CONCLUSIONS: ET for
      VAA is safe and effective; however, SVAA has a significantly higher 30-day
      mortality rate than ASVAA.

PMID- 27050197
TI  - Advice to young surgeons.

PMID- 27050198
TI  - The impact of endovascular aneurysm repair on mortality for elective abdominal
      aortic aneurysm repair in England and the United States.
AB  - BACKGROUND: Procedural mortality is of paramount importance for patients
      undergoing elective abdominal aortic aneurysm (AAA) repair. Previous comparative
      studies have demonstrated international differences in the care of ruptured AAA.
      This study compared the use of endovascular aneurysm repair (EVAR) and in
      hospital mortality for elective AAA repair in England and the United States.
      METHODS: The English Hospital Episode Statistics and the U.S. Nationwide
      Inpatient Sample (NIS) were interrogated for elective AAA repair from 2005 to
      2010. In-hospital mortality and the use of EVAR were analyzed separately for each
      health care system, after within-country risk adjustment for age, gender, year,
      and an accepted national comorbidity index. RESULTS: The study included 21,272
      patients with AAA in England, of whom 86.61% were male, with median
      (interquartile range) age of 74 (69-79) years. There were 196,113 AAA patients in
      the United States, of whom 76.14% were male, with median (interquartile range)
      age of 73 (67-78) years. In-hospital mortality was greater in England (4.09% vs
      1.96 %; P < .01) and EVAR less common (37.33% vs 64.36%; P < .01). These
      observations persisted in age- and gender-matched comparison. In both countries,
      lower mortality and greater use of EVAR were seen in centers performing greater
      numbers of AAA repairs per annum. In England, lower mortality and greater use of
      EVAR were seen in teaching hospitals with larger bed capacity. CONCLUSIONS: In
      hospital survival and the uptake of EVAR are lower in England than in the United
      States. In both countries, mortality was lowest in high-caseload centers
      performing a greater proportion of cases with endovascular repair. These common
      factors suggest strategies for improving outcomes for patients requiring elective
      AAA repair.

PMID- 27050199
TI  - Different recombinant forms of polyphenol oxidase A, a laccase from Marinomonas
      mediterranea.
AB  - Polyphenol oxidase from the marine bacterium Marinomonas mediterranea (MmPPOA) is
      a membrane-bound, blue, multi-copper laccase of 695 residues. It possesses
      peculiar properties that distinguish it from known laccases, such as a broad
      substrate specificity (common to tyrosinases) and a high redox potential. In
      order to push the biotechnological application of this laccase, the full-length
      enzyme was overexpressed in Escherichia coli cells with and without a C-terminal
      His-tag. The previous form, named rMmPPOA-695-His, was purified to homogeneity by
      HiTrap chelating chromatography following solubilization by 1% SDS in the lysis
      buffer with an overall yield of ~1 mg/L fermentation broth and a specific
      activity of 1.34 U/mg protein on 2,6-dimethoxyphenol as substrate. A truncated
      enzyme form lacking 58 residues at the N-terminus encompassing the putative
      membrane binding region, namely rMmPPOA-637-His, was successfully expressed in E.
      coli as soluble protein and was purified by using the same procedure set-up as
      for the full-length enzyme. Elimination of the N-terminal sequence decreased the
      specific activity 15-fold (which was partially restored in the presence of 1 M
      NaCl) and altered the secondary and tertiary structures and the pH dependence of
      optimal stability. The recombinant rMmPPOA-695-His showed kinetic properties on
      catechol higher than for known laccases, a very high thermal stability, and a
      strong resistance to NaCl, DMSO, and Tween-80, all properties that are required
      for specific, targeted industrial applications.

PMID- 27050200
TI  - Narrowing the Gap? Describing women's outcomes in Midwifery Group Practice in
      remote Australia.
AB  - BACKGROUND: In Australia, Aboriginal women and babies experience higher maternal
      and perinatal morbidity and mortality rates than their non-Aboriginal
      counterparts. Whilst midwifery led continuity of care has been shown to be safe
      for women and their babies, with benefits including reducing the preterm birth
      rate, access to this model of care in remote areas remains limited. A Midwifery
      Group Practice was established in 2009 in a remote city of the Northern
      Territory, Australia, with the aim of improving outcomes and access to midwifery
      continuity of care. AIM: The aim of this paper is to describe the maternal and
      newborn outcomes for women accessing midwifery continuity of care in a remote
      context in Australia. METHODS: A retrospective descriptive design using data from
      two existing electronic databases was undertaken and analysed descriptively.
      FINDINGS: In total, 763 women (40% of whom were Aboriginal) gave birth to 769
      babies over a four year period. There were no maternal deaths and the rate of
      perinatal mortality was lower than that across the Northern Territory. Lower
      rates of preterm birth (6%) and low birth weight babies (5%) were found in
      comparison to population based data. CONCLUSION: Continuity of Midwifery Care can
      be effectively provided to remote dwelling Aboriginal women and appears to
      improve outcomes for women and their infants.

PMID- 27050201
TI  - Vulnerability to depression is associated with a failure to acquire implicit
      social appraisals.
AB  - Major depressive disorder (MDD) is associated with disrupted relationships with
      partners, family, and peers. These problems can precipitate the onset of clinical
      illness, influence severity and the prospects for recovery. Here, we investigated
      whether individuals who have recovered from depression use interpersonal signals
      to form favourable appraisals of others as social partners. Twenty recovered
      depressed adults (with >1 adult episode of MDD but euthymic and medication-free
      for six months) and 23 healthy, never-depressed adults completed a task in which
      the gaze direction of some faces reliably cued the location a target (valid
      faces), whereas other faces cued the opposite location (invalid faces). No
      participants reported awareness of this contingency, and both groups were
      significantly faster to categorise targets following valid compared with invalid
      gaze cueing faces. Following this task, participants judged the trustworthiness
      of the faces. Whereas the healthy never-depressed participants judged the valid
      faces to be significantly more trustworthy than the invalid faces; this implicit
      social appraisal was absent in the recovered-depressed participants. Individuals
      who have recovered from MDD are able to respond appropriately to joint attention
      with other people but appear to not use joint attention to form implicit trust
      appraisals of others as potential social partners.

PMID- 27050202
TI  - Seeking environmental causes of neurodegenerative disease and envisioning primary
      prevention.
AB  - Pathological changes of the aging brain are expressed in a range of
      neurodegenerative disorders that will impact increasing numbers of people across
      the globe. Research on the causes of these disorders has focused heavily on
      genetics, and strategies for prevention envision drug-induced slowing or
      arresting disease advance before its clinical appearance. We discuss a strategic
      shift that seeks to identify the environmental causes or contributions to
      neurodegeneration, and the vision of primary disease prevention by removing or
      controlling exposure to culpable agents. The plausibility of this approach is
      illustrated by the prototypical neurodegenerative disease amyotrophic lateral
      sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long
      latency disease, once thought to be an inherited genetic disorder but now known
      to have a predominant or exclusive environmental origin, is in the process of
      disappearing from the three heavily affected populations, namely Chamorros of
      Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai
      linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure
      via traditional food and/or medicine (the only common exposure in all three
      geographic isolates) to one or more neurotoxins in seed of cycad plants is the
      most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at
      exposure might explain the stratified epidemic of neurodegenerative disease on
      Guam in which high-incidence ALS peaked and declined before that of PD, only to
      be replaced today by a dementing disorder comparable to Alzheimer's disease.
      Exposure to the Guam environment is also linked to the delayed development of ALS
      among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of
      which is reported here for the first time. Lessons learned from this study and
      from 65 years of research on ALS-PDC include the exceptional value of initial,
      field-based informal investigation of disease-affected individuals and
      communities, the results of which can provide an invaluable guide to steer cogent
      epidemiological and laboratory-based research.

PMID- 27050203
TI  - Evidence, Policy, and E-Cigarettes--Will England Reframe the Debate?

PMID- 27050204
TI  - When Is It Ethical to Withhold Prevention?

PMID- 27050207
TI  - Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting.

PMID- 27050208
TI  - IMAGES IN CLINICAL MEDICINE. Reversible Loss of Vision in Malignant Hypertension.

PMID- 27050206
TI  - Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma.
AB  - BACKGROUND: Grade 2 gliomas occur most commonly in young adults and cause
      progressive neurologic deterioration and premature death. Early results of this
      trial showed that treatment with procarbazine, lomustine (also called CCNU), and
      vincristine after radiation therapy at the time of initial diagnosis resulted in
      longer progression-free survival, but not overall survival, than radiation
      therapy alone. We now report the long-term results. METHODS: We included patients
      with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger
      than 40 years of age and had undergone subtotal resection or biopsy or who were
      40 years of age or older and had undergone biopsy or resection of any of the
      tumor. Patients were stratified according to age, histologic findings, Karnofsky
      performance-status score, and presence or absence of contrast enhancement on
      preoperative images. Patients were randomly assigned to radiation therapy alone
      or to radiation therapy followed by six cycles of combination chemotherapy.
      RESULTS: A total of 251 eligible patients were enrolled from 1998 through 2002.
      The median follow-up was 11.9 years; 55% of the patients died. Patients who
      received radiation therapy plus chemotherapy had longer median overall survival
      than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard
      ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10
      years was 51% in the group that received radiation therapy plus chemotherapy
      versus 21% in the group that received radiation therapy alone; the corresponding
      rates of overall survival at 10 years were 60% and 40%. A Cox model identified
      receipt of radiation therapy plus chemotherapy and histologic findings of
      oligodendroglioma as favorable prognostic variables for both progression-free and
      overall survival. CONCLUSIONS: In a cohort of patients with grade 2 glioma who
      were younger than 40 years of age and had undergone subtotal tumor resection or
      who were 40 years of age or older, progression-free survival and overall survival
      were longer among those who received combination chemotherapy in addition to
      radiation therapy than among those who received radiation therapy alone. (Funded
      by the National Cancer Institute and others; ClinicalTrials.gov number,
      NCT00003375.).

PMID- 27050205
TI  - Fresh Fruit Consumption and Major Cardiovascular Disease in China.
AB  - BACKGROUND: In Western populations, a higher level of fruit consumption has been
      associated with a lower risk of cardiovascular disease, but little is known about
      such associations in China, where the consumption level is low and rates of
      stroke are high. METHODS: Between 2004 and 2008, we recruited 512,891 adults, 30
      to 79 years of age, from 10 diverse localities in China. During 3.2 million
      person-years of follow-up, 5173 deaths from cardiovascular disease, 2551 incident
      major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3523
      intracerebral hemorrhages were recorded among the 451,665 participants who did
      not have a history of cardiovascular disease or antihypertensive treatments at
      baseline. Cox regression yielded adjusted hazard ratios relating fresh fruit
      consumption to disease rates. RESULTS: Overall, 18.0% of participants reported
      consuming fresh fruit daily. As compared with participants who never or rarely
      consumed fresh fruit (the "nonconsumption" category), those who ate fresh fruit
      daily had lower systolic blood pressure (by 4.0 mm Hg) and blood glucose levels
      (by 0.5 mmol per liter [9.0 mg per deciliter]) (P<0.001 for trend for both
      comparisons). The adjusted hazard ratios for daily consumption versus
      nonconsumption were 0.60 (95% confidence interval [CI], 0.54 to 0.67) for
      cardiovascular death, and 0.66 (95% CI, 0.58 to 0.75), 0.75 (95% CI, 0.72 to
      0.79), and 0.64 (95% CI, 0.56 to 0.74), respectively, for incident major coronary
      events, ischemic stroke, and hemorrhagic stroke. There was a strong log-linear
      dose-response relationship between the incidence of each outcome and the amount
      of fresh fruit consumed. These associations were similar across the 10 study
      regions and in subgroups of participants defined by baseline characteristics.
      CONCLUSIONS: Among Chinese adults, a higher level of fruit consumption was
      associated with lower blood pressure and blood glucose levels and, largely
      independent of these and other dietary and nondietary factors, with significantly
      lower risks of major cardiovascular diseases. (Funded by the Wellcome Trust and
      others.).

PMID- 27050209
TI  - CLINICAL PROBLEM-SOLVING. A Deficient Diagnosis.

PMID- 27050210
TI  - Antenatal Glucocorticoids for Late Preterm Birth?

PMID- 27050211
TI  - Clinical Effect of Surgical Volume.

PMID- 27050212
TI  - Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.

PMID- 27050213
TI  - Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.

PMID- 27050214
TI  - Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.

PMID- 27050215
TI  - Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.

PMID- 27050216
TI  - A 21-Gene Expression Assay in Breast Cancer.

PMID- 27050217
TI  - A 21-Gene Expression Assay in Breast Cancer.

PMID- 27050218
TI  - A 21-Gene Expression Assay in Breast Cancer.

PMID- 27050219
TI  - Dengue Vaccine in Regions of Endemic Disease.

PMID- 27050220
TI  - Dengue Vaccine in Regions of Endemic Disease.

PMID- 27050221
TI  - Dengue Vaccine in Regions of Endemic Disease.

PMID- 27050222
TI  - Endobronchial Valves for Emphysema.

PMID- 27050223
TI  - Endobronchial Valves for Emphysema.

PMID- 27050224
TI  - Germline Mutations in Predisposition Genes in Pediatric Cancer.

PMID- 27050225
TI  - Germline Mutations in Predisposition Genes in Pediatric Cancer.

PMID- 27050226
TI  - ALS-008176 for Respiratory Syncytial Virus Infection.

PMID- 27050227
TI  - ALS-008176 for Respiratory Syncytial Virus Infection.

PMID- 27050228
TI  - Cardiac Complications and Major Noncardiac Surgery.

PMID- 27050229
TI  - Cardiac Complications and Major Noncardiac Surgery.

PMID- 27050230
TI  - Cardiac Complications and Major Noncardiac Surgery.

PMID- 27050231
TI  - Cardiac Complications and Major Noncardiac Surgery.

PMID- 27050232
TI  - Intensity of Chronic Pain.

PMID- 27050233
TI  - Intensity of Chronic Pain.

PMID- 27050234
TI  - Cinacalcet for Symptomatic Hypercalcemia Caused by AP2S1 Mutations.

PMID- 27050235
TI  - IMAGES IN CLINICAL MEDICINE. Creeping Eruption--Cutaneous Larva Migrans.

PMID- 27050236
TI  - Assessing movement quality in persons with severe mental illness - Reliability
      and validity of the Body Awareness Scale Movement Quality and Experience.
AB  - Motor disturbances and disturbed self-recognition are common features that affect
      mobility in persons with schizophrenia spectrum disorder and bipolar disorder.
      Physiotherapists in Scandinavia assess and treat movement difficulties in persons
      with severe mental illness. The Body Awareness Scale Movement Quality and
      Experience (BAS MQ-E) is a new and shortened version of the commonly used Body
      Awareness Scale-Health (BAS-H). The purpose of this study was to investigate the
      inter-rater reliability and the concurrent validity of BAS MQ-E in persons with
      severe mental illness. The concurrent validity was examined by investigating the
      relationships between neurological soft signs, alexithymia, fatigue, anxiety, and
      mastery. Sixty-two persons with severe mental illness participated in the study.
      The results showed a satisfactory inter-rater reliability (n = 53) and a
      concurrent validity (n = 62) with neurological soft signs, especially cognitive
      and perceptual based signs. There was also a concurrent validity linked to
      physical fatigue and aspects of alexithymia. The scores of BAS MQ-E were in
      general higher for persons with schizophrenia compared to persons with other
      diagnoses within the schizophrenia spectrum disorders and bipolar disorder. The
      clinical implications are presented in the discussion. 

PMID- 27050237
TI  - Long-term risk of colorectal cancer by gender after positive colonoscopy:
      population-based cohort study.
AB  - BACKGROUND: Evidence for surveillance intervals of colonoscopy are primarily
      based on adenoma recurrence rate rather than on colorectal cancer (C.R.C.)
      incidence. Little is known about long-term risk of C.R.C. after positive
      colonoscopy. In view of men have significantly higher C.R.C. risk than women, we
      aimed to estimate the gender-specific C.R.C. incidence after positive colonoscopy
      (adenoma or malignant lesion) at follow-up colonoscopy. METHODS: A retrospective
      cohort study was conducted using data from a database of colonoscopy screening
      and surveillance. Patients having had a colonoscopy (January 2010-March 2014)
      were selected as study subjects and the history of prior colonoscopies was
      reviewed. Multivariable Weibull regression models were used to estimate the
      incidence of C.R.C. at follow-up colonoscopy for subjects who were assigned a
      stratified risk level. The benchmark risk was defined according to a national
      survey. RESULTS: The interval incidence of C.R.C. at a 10 year follow-up was 164
      (95% C.I. 63-343) and 79 (95% C.I. 26-188) per 100,000 person-years for low-risk
      men and women respectively, which tallied with our benchmark risk. Men exceeded
      the benchmark risk in 3-5 years if they had an incomplete polyp removal, >=3
      adenomas during their last colonoscopy or a personal C.R.C. history, and in 7-8
      years if they only had familial C.R.C. HISTORY: Women had a lower risk of C.R.C.,
      and reached a same risk level 3-5 years later than men. Coexisting above risk
      factors resulted in a sharp increase in the incidence of C.R.C. at follow-up
      exceeding the benchmark much earlier. CONCLUSION: Surveillance intervals for men
      based on incidence of C.R.C. are in line with that recommended by the current
      guidelines for colonoscopy. However, an extension of 3-5 years may be appropriate
      for women. To target personalized medicine, a risk predictive model could be used
      to identify an appropriate surveillance interval for each individual in the
      future.

PMID- 27050239
TI  - Can umbilical artery Doppler findings at 36 weeks' gestation predict maternal
      hypertension at later gestation?
AB  - OBJECTIVES: To clarify whether ultrasonographic evaluations of fetoplacental
      underperfusion using umbilical artery (UmA) Doppler indices at 36 weeks'
      gestation can predict maternal hypertension at later gestation. METHODS:
      Normotensive pregnant women who underwent an ultrasound scan at 36 weeks'
      gestation and delivered singleton infants at term between 2012 and 2013 were
      prospectively enrolled. UmA Doppler and maternal blood pressure results at 36
      weeks' gestation in cases with pregnancy-induced hypertension (PIH) at later
      gestation were compared with a control group. RESULTS: Thirty-nine and 775 cases
      were classified into the PIH and control group, respectively. The UmA pulsatility
      index (PI) and maternal systolic blood pressure (SBP) at 36 weeks' gestation were
      higher in the PIH group than in control group (UmA-PI: 0.88 vs. 0.80, p = 0.002;
      SBP: 126 mmHg vs. 112 mmHg, p < 0.001). The area under the ROC curve for the
      prediction of PIH by combining the UmA-PI and SBP was 0.867 (95% confidence
      interval (CI): 0.781, 0.954). The detection rate for PIH was 64.0% with a 10%
      false-positive rate. CONCLUSIONS: An increased UmA-PI at 36 weeks' gestation is
      associated with the occurrence of PIH at later gestation. This result may
      indicate the possibility to detect fetoplacental underperfusion ultrasonically.

PMID- 27050238
TI  - Associations Between Body Weight Status and Substance Use Among African American
      Women in Baltimore, Maryland: The CHAT Study.
AB  - BACKGROUND: Studies on associations between body weight status and specific
      substance use have provided conflicting findings. OBJECTIVES: This paper
      investigated the association between substance use and body weight status among
      African American women. METHODS: We analyzed the data from 328 African American
      women who were enrolled in a HIV prevention intervention in Baltimore, MD, USA,
      in order to investigate the association between substance use and their body
      weight status. Participants' anthropometry was measured by trained research
      staff. Substance use information was collected via self-administered and
      interviewer-administered questionnaires. RESULTS: About 33.4% were classified as
      normal/underweight, 24.2% overweight, and 42.4% obese. Compared to overweight
      (38.5%) and obese (29.2%) participants, the normal/underweight women had
      significantly higher prevalence of drug use (52.8%) (chi(2)= 14.11, p < 0.05).
      BMI was significantly negatively associated with current heroin use (t = -2.21, p
      < 0.05). The risk of being overweight and obesity was lower among active
      marijuana (z = -2.05, p < 0.05) and heroin users (z = -1.91, p < 0.10) than among
      non-marijuana/non-heroin users. Heroin smokers had lower body weight (t = -3.02,
      p < 0.05) and BMI (t = -2.47, p < 0.05) than non-heroin smokers. The decrease in
      BMI appeared to be greater among more frequent (>=once/day) heroin users (t = 
      2.39, p <0.05) as compared to the less frequent heroin users (<once/day) (t = 
      1.71, p < 0.10), but this difference was not statistically significant.
      CONCLUSIONS: The results are comparable to existing findings. Active marijuana
      and heroin users were less likely to be overweight and obese compared to their
      counterparts. The impact of substance use on body weight status differed by the
      frequency and route of administration.

PMID- 27050240
TI  - Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor
      efficacy.
AB  - Blinatumomab is a member of a novel class of T cell-engaging bispecific
      antibodies, so-called Bispecific T cell Engager (BiTEs). It is directed against
      the B cell differentiation antigen CD19 and intended for treatment of B cell
      malignancies. In clinical phase I/II trials, blinatumomab showed remarkable
      single-agent activity in patients with relapsed and/or refractory (R/R) non
      Hodgkin lymphoma and R/R B cell precursor acute lymphoblastic leukemia (B
      precursor ALL). Cytokine release syndrome and neurological side effects were dose
      limiting. Adverse effects were well manageable and transient in nature. Based on
      results of an international phase II trial, blinatumomab received FDA approval
      for the treatment of R/R B-precursor ALL in December 2014. Ongoing and future
      trials will contribute to further optimization of blinatumomab-based T cell
      therapy and have to show that integration of blinatumomab in current and
      innovative treatment protocols improves overall survival and quality of life of
      patients with B cell malignancies. 

PMID- 27050241
TI  - Effects of High-Velocity Resistance Training on Athletic Performance in
      Prepuberal Male Soccer Athletes.
AB  - Negra, Y, Chaabene, H, Hammami, M, Hachana, Y, and Granacher, U. Effects of high
      velocity resistance training on athletic performance in prepuberal male soccer
      athletes. J Strength Cond Res 30(12): 3290-3297, 2016-The aim of this study was
      to assess the effectiveness of a 12-week in-season low-to-moderate load high
      velocity resistance training (HVRT) in addition to soccer training as compared
      with soccer training only on proxies of athletic performance in prepubertal
      soccer players. Twenty-four male soccer players performed 2 different protocols:
      (a) regular soccer training with 5 sessions per week (n = 11; age = 12.7 +/- 0.3
      years) and (b) regular soccer training with 3 sessions per week and HVRT with 2
      sessions per week (n = 13; age = 12.8 +/- 0.2 years). The outcome measures
      included tests for the assessment of muscle strength (e.g., 1 repetition maximum
      [1RM] half-squat tests), jump ability (e.g., countermovement jump, squat jump
      [SJ], standing long jump [SLJ], and multiple 5-bound tests [MB5s]), linear speed
      (e.g., 5-, 10-, 20-, and 30-m sprint tests), and change of direction (e.g., T
      test and Illinois change of direction test). Results revealed significant group *
      test interactions for the SJ test (p <= 0.05, d = 0.59) and the SLJ test (p <
      0.01, d = 0.83). Post hoc tests illustrated significant pre-post changes in the
      HVRT group (SJ: [INCREMENT]22%, p < 0.001, d = 1.26; SLJ: [INCREMENT]15%, p <
      0.001, d = 1.30) but not in the control group. In addition, tendencies toward
      significant interaction effects were found for the 1RM half-squat (p = 0.08, d =
      0.54) and the 10-m sprint test (p = 0.06, d = 0.57). Significant pre-post changes
      were found for both parameters in the HVRT group only (1RM: [INCREMENT]25%, p <
      0.001, d = 1.23; 10-m sprint: [INCREMENT]7%, p < 0.0001, d = 1.47). In summary,
      in-season low-to-moderate load HVRT conducted in combination with regular soccer
      training is a safe and feasible intervention that has positive effects on maximal
      strength, vertical and horizontal jump and sprint performance as compared with
      soccer training only.

PMID- 27050242
TI  - Technical Actions, Heart Rate, and Locomotor Activity in 7v7 and 8v8 Games for
      Female Youth Soccer Players.
AB  - Orntoft, C, Larsen, MN, Andersen, TB, Rasmussen, LS, Povoas, SCA, Randers, MB,
      and Krustrup, P. Technical actions, heart rate, and locomotor activity in 7v7 and
      8v8 games for female youth soccer players. J Strength Cond Res 30(12): 3298-3303,
      2016-The purpose of this study was to evaluate technical performance, heart rate
      (HR), and activity profile in 7v7 and 8v8 soccer games for 9- to 10-year-old
      girls (U11). A total of 24 female youth players participated in the study, all
      playing 20-minute 7v7 and 8v8 games with 160 and 223 m per player, respectively.
      Technical actions, HR, and activity profile were measured during the games using
      video filming, HR monitors, and 5-Hz Global positioning system (GPS) units. The
      number of technical actions was higher in 7v7 than in 8v8 games (34 +/- 19 vs. 28
      +/- 14; p = 0.03; d = 0.37), as was the number of successful actions (25 +/- 16
      vs. 20 +/- 12; p = 0.01; d = 0.35), with no difference in success rate for
      technical actions (70 +/- 13 vs. 69 +/- 14%; p = 0.63; d = 0.07). No differences
      were found between 7v7 and 8v8 in total distance covered (1,574 +/- 251 and 1,622
      +/- 281 m; p = 0.66; d = 0.18), peak speed (19.5 +/- 2.6 and 20.7 +/- 1.5 km.h; p
      = 0.16; d = 0.56), mean HR values (85 +/- 5 and 86 +/- 6%HRpeak; p = 0.85; d =
      0.18), and time of >90% HRpeak (37 +/- 16 and 35 +/- 14% of playing time; p =
      0.70; d = 0.13). Distance covered at the highest running speeds of >16 km.h was
      lower in 7v7 than in 8v8 games (34 +/- 24 vs. 63 +/- 34 m; p = 0.018; d = 0.98),
      as was the number of entries into this speed zone (8 +/- 5 vs. 13 +/- 7; p =
      0.006; d = 0.82). In conclusion, more technical actions and successful actions
      were observed in 7v7 than in 8v8 games, but players covered more ground with high
      speed running in 8v8 games. This study also revealed that HR values were high in
      both game formats for U11 adolescent female players, with no difference between
      formats.

PMID- 27050243
TI  - Total Hemoglobin Mass, Aerobic Capacity, and HBB Gene in Polish Road Cyclists.
AB  - Malczewska-Lenczowska, J, Orysiak, J, Majorczyk, E, Zdanowicz, R, Szczepanska, B,
      Starczewski, M, Kaczmarski, J, Dybek, T, Pokrywka, A, Ahmetov, II, and Sitkowski,
      D. Total hemoglobin mass, aerobic capacity, and the HBB gene in polish road
      cyclists. J Strength Cond Res 30(12): 3512-3519, 2016-The relationship between
      genes, amount of hemoglobin, and physical performance are still not clearly
      defined. The aim of this study was to examine the association between-551C/T and
      intron 2, +16 C/G polymorphisms in the beta hemoglobin (HBB) gene and total
      hemoglobin mass (tHbmass) and aerobic capacity in endurance athletes. Total
      hemoglobin mass and aerobic capacity indices, i.e.,V[Combining Dot Above]O2max,
      oxygen uptake at anaerobic threshold (V[Combining Dot Above]O2AT), maximal power
      output (Pmax), and power at anaerobic threshold (PAT) were determined in 89 young
      road cyclists, female (n = 39) and male (n = 50), who were genotyped for 2
      polymorphisms in the HBB gene. The relative values of aerobic capacity indices
      differed significantly among intron 2, +16 C/G polymorphisms of the HBB gene only
      in female cyclists; athletes with GG genotype had significantly higher values of
      V[Combining Dot Above]O2max (p = 0.003), V[Combining Dot Above]O2AT (p = 0.007),
      PAT (p = 0.015), and Pmax (p = 0.004) than C carriers. No relationships were
      found between the C-carrier model (CC + CG vs. GG in the case of intron 2, +16
      C/G and CC + CT vs. TT for -551 C/T polymorphisms of the HBB gene) and relative
      values of tHbmass. Our results demonstrated that the HBB gene could be related to
      aerobic capacity, but it seems that it does not result from an increase in the
      amount of hemoglobin in the blood.

PMID- 27050244
TI  - Ingestion of a Nitric Oxide Enhancing Supplement Improves Resistance Exercise
      Performance.
AB  - Mosher, SL, Sparks, SA, Williams, EL, Bentley, DJ, and Mc Naughton, LR. Ingestion
      of a nitric oxide enhancing supplement improves resistance exercise performance.
      J Strength Cond Res 30 (12): 3520-3524, 2016-Studies have established that
      supplementation of nitrate increases nitric oxide which in turn improves exercise
      performance. The current study aimed to investigate the effects of nitrate
      ingestion on performance of bench press resistance exercise until failure. Twelve
      recreationally active (age, 21 +/- 2 years, height, 177.2 +/- 4.0 cm, weight,
      82.49 +/- 9.78 kg) resistance-trained men participated in the study. The study
      used a double-blind, randomized cross-over design, where participants ingested
      either 70 ml of "BEET It Sport" nitrate shot containing 6.4 millimoles (mmol.L)
      or 400 mg of nitrate or a blackcurrant placebo drink. Participants completed a
      resistance exercise session, consisting of bench press exercise at an intensity
      of 60% of their established 1 repetition maximum (1RM), for 3 sets until failure
      with 2 minutes rest interval between sets. The repetitions completed, total
      weight lifted, local and general rate of perceived exertion (RPE), and blood
      lactate were all measured. The results showed a significant difference in
      repetitions to failure (p <= 0.001) and total weight lifted (p <= 0.001).
      However, there were no significant difference between blood lactate over the 2
      trials (p = 0.238), and no difference in Local (p = 0.807) or general (p = 0.420)
      indicators of fatigue as measured by RPE. This study demonstrates that nitrate
      supplementation has the potential to improve resistance training performance and
      work output compared with a placebo.

PMID- 27050245
TI  - Photobiomodulation Therapy Improves Performance and Accelerates Recovery of High
      Level Rugby Players in Field Test: A Randomized, Crossover, Double-Blind, Placebo
      Controlled Clinical Study.
AB  - Pinto, HD, Vanin, AA, Miranda, EF, Tomazoni, SS, Johnson, DS, Albuquerque-Pontes,
      GM, de Oliveira Aleixo Junior, I, Grandinetti, VdS, Casalechi, HL, de Tarso
      Camillo de Carvalho, P, and Pinto Leal Junior. Photobiomodulation therapy
      improves performance and accelerates recovery of high-level rugby players in
      field test: A randomized, crossover, double-blind, placebo-controlled clinical
      study. J Strength Cond Res 30(12): 3329-3338, 2016-Although growing evidence
      supports the use of photobiomodulation therapy (PBMT) for performance and
      recovery enhancement, there have only been laboratory-controlled studies.
      Therefore, the aim of this study was to analyze the effects of PBMT in
      performance and recovery of high-level rugby players during an anaerobic field
      test. Twelve male high-level rugby athletes were recruited in this randomized,
      crossover, double-blinded, placebo-controlled trial. No interventions were
      performed before the Bangsbo sprint test (BST) at familiarization phase (week 1);
      at weeks 2 and 3, pre-exercise PBMT or placebo were randomly applied to each
      athlete. Photobiomodulation therapy irradiation was performed at 17 sites of each
      lower limb, employing a cluster with 12 diodes (4 laser diodes of 905 nm, 4 light
      emitting diodes [LEDs] of 875 nm, and 4 LEDs of 640 nm, 30 J per site,
      manufactured by Multi Radiance Medical). Average time of sprints, best time of
      sprints, and fatigue index were obtained from BST. Blood lactate levels were
      assessed at baseline, and at 3, 10, 30, and 60 minutes after BST. Athletes'
      perceived fatigue was also assessed through a questionnaire. Photobiomodulation
      therapy significantly (p <= 0.05) improved the average time of sprints and
      fatigue index in BST. Photobiomodulation therapy significantly decreased
      percentage of change in blood lactate levels (p <= 0.05) and perceived fatigue (p
      <= 0.05). Pre-exercise PBMT with the combination of super-pulsed laser (low-level
      laser), red LEDs, and infrared LEDs can enhance performance and accelerate
      recovery of high-level rugby players in field test. This opens a new avenue for
      wide use of PBMT in real clinical practice in sports settings.

PMID- 27050246
TI  - Influence of Cognitive Interferences and Self-Talk Functions on Performance
      During Competition in Elite Female Field Hockey Players.
AB  - Perez-Encinas, C, Fernandez-Campos, FJ, Rodas, G, and Barrios, C. Influence of
      cognitive interferences and self-talk functions on performance during competition
      in elite female field hockey players. J Strength Cond Res 30(12): 3339-3346, 2016
      Cognitive interferences in the form of distracting thoughts and self-talk
      functions may play an important role in athletes' performance. The purpose of
      this study was to explore the types of interfering thoughts and the concomitant
      use of self-talk functions occurring in a sample of elite female field hockey
      players. The variation in these interferences in relation to athletes'
      performance level in competition was also investigated. Thirty-two female players
      of the first and the Under-21 National Team completed the Thought Occurrence
      Questionnaire for Sport and the Self-Talk Questionnaire after an international
      competition. The trainer rated the players' performance during competition in 3
      different categories according to his expectancies based on the athletes'
      conditioning: Low (n = 6), Normal (n = 15), and High Performance (n = 11). Those
      players classified as low performing had increased the occurrence of irrelevant
      thoughts as compared with other groups. These athletes also showed the highest
      scores on the thoughts of escape subscale. Athletes with high performance during
      tournaments exhibited the lowest scores on all subscales, especially in thoughts
      of escape. The S-TQ subscales showed no differences among the 3 performance
      groups. Under-21 players had higher scores on the occurrence of performance
      worries and thoughts of escape subscales than first national team players.
      Interfering thoughts are common in female field hockey players during world-class
      competitions. The occurrence of irrelevant thoughts and thoughts of escape was
      related to players exhibiting low performance. The use of self-talk functions was
      relatively low in these athletes and could explain the enhanced occurrence of
      interfering thoughts.

PMID- 27050247
TI  - Performance Analysis of Surfing: A Review.
AB  - Farley, ORL, Abbiss, CR, and Sheppard, JM. Performance Analysis of Surfing: A
      Review. J Strength Cond Res 31(1): 260-271, 2017-Despite the increased
      professionalism and substantial growth of surfing worldwide, there is limited
      information available to practitioners and coaches in terms of key performance
      analytics that are common in other field-based sports. Indeed, research analyzing
      surfing performance is limited to a few studies examining male surfers' heart
      rates, surfing activities through time-motion analysis (TMA) using video
      recordings and Global Positioning Satellite (GPS) data during competition and
      recreational surfing. These studies have indicated that specific activities
      undertaken during surfing are unique with a variety of activities (i.e.,
      paddling, resting, wave riding, breath holding, and recovery of surfboard in the
      surf). Furthermore, environmental and wave conditions also seem to influence the
      physical demands of competition surfing. It is due to these demands that surfers
      are required to have a high cardiorespiratory fitness, high muscular endurance,
      and considerable strength and anaerobic power, particular within the upper torso.
      By exploring various methods of performance analysis used within other sports, it
      is possible to improve our understanding of surfing demands. In so doing this
      will assist in the development of protocols and strategies to assess
      physiological characteristics of surfers, monitor athlete performance, improve
      training prescription, and identify talent. Therefore, this review explores the
      current literature to provide insights into methodological protocols,
      delimitations of research into athlete analysis and an overview of surfing
      dynamics. Specifically, this review will describe and review the use of TMA, GPS,
      and other technologies (i.e., HR) that are used in external and internal load
      monitoring as they pertain to surfing.

PMID- 27050248
TI  - Synthesis of some tetrahydropyrimidine-5-carboxylates, determination of their
      metal chelating effects and inhibition profiles against acetylcholinesterase,
      butyrylcholinesterase and carbonic anhydrase.
AB  - 2-(Methacryloyloxy)ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5
      carboxylate, is a cyclic urea derivative synthesized from urea, 2
      (methacryloyloxy) ethyl acetoacetate and substituted benzaldehyde, and tested in
      terms of the inhibition of two physiologically relevant carbonic anhydrase (CA)
      isozymes I and II. Acetylcholinesterase (AChE) is found in high concentrations in
      the red blood cells and brain. Butyrylcholinesterase (BChE) is another enzyme
      abundantly present in the liver and released into blood in a soluble form. Also,
      they were tested for the inhibition of AChE and BChE enzymes and demonstrated
      effective inhibition profiles with Ki values in the range of 429.24-530.80 nM
      against hCA I, 391.86-530.80 nM against hCA II, 68.48-97.19 nM against AChE and
      104.70-214.15 nM against BChE. On the other hand, acetazolamide clinically used
      as CA inhibitor, showed Ki value of 281.33 nM against hCA I, and 202.70 nM
      against hCA II. Also, Tacrine inhibited AChE and BChE showed Ki values of 396.03
      and 209.21 nM, respectively. 

PMID- 27050249
TI  - Effects of Proanthocyanidins on Intestinal Motility Disturbance Following
      Intestinal Ischemia/Reperfusion.
AB  - PURPOSE: To investigate the potential protective effects of
      Proanthocyanidins(PAs) on intestinal motility disturbance following intestinal
      ischemia/reperfusion (I/R). MATERIALS AND METHODS: Male rats were divided into
      four groups: Sham, I/R, I/R+PA100 and I/R+PA200. Sham group underwent laparotomy
      without ligation, the others were subjected to intestinal ischemia for 1 h and
      reperfusion 4 h. Rats in the I/R+PA100 group received PAs (100 mg/kg/d) for 5
      days prior to I/R, while rats in the I/R+PA200 group received PAs (200 mg/kg/d).
      After reperfusion, using an electrophysiology instrument measured ileal slow
      wave. Ileal specimens were obtained to determine contractility, tissue levels of
      Bax, Bcl-2, and Caspase-3 and evaluate histopathological changes. In addition,
      blood sample was obtained to determine serum superoxide dismutase (SOD) activity
      and malondialdehyde (MDA) levels. RESULTS: Intestinal I/R caused severe
      histopathological injury including mucosal erosions, inflammatory cell
      infiltration, necrosis, and hemorrhage. Both PAs treatment decreased mucosal
      pathological impairment in comparison with the I/R group (p < .05) in light
      microscopic evaluations. In both PAs-treated groups, Bax and Caspase-3 expression
      were decreased compared to I/R group, while the Bcl-2 expression increased (p <
      .05), which was similarly the case for serum SOD activity demonstrated
      significant enhance (p < .05) and decline in MDA levels in comparison with I/R
      group (both p < .05). Moreover, PAs treatment was more efficient in attenuating
      serum MDA levels of intestinal I/R (both p < .05). And the contractile amplitude
      and frequency of slow wave in I/R+PA100 and I/R+PA200 groups were higher than I/R
      group (both p < .05). CONCLUSIONS: PAs improve intestinal motility disturbance
      following intestinal I/R by alleviating oxidative stress and apoptosis.

PMID- 27050250
TI  - RS3PE revisited: a systematic review and meta-analysis of 331 cases.
AB  - OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting oedema
      (RS(3)PE) syndrome is a rare inflammatory arthritis, characterised by symmetrical
      distal synovitis, pitting oedema of the hands and feet, absence of rheumatoid
      factor, and favourable response to glucocorticoids. The aim of our study is to
      further delineate the clinical and laboratory features, and response to
      treatment. METHODS: We performed a systematic electronic search of Medline,
      PubMed, EMBASE, ACR and EULAR databases for case reports, case series, and
      related articles of RS(3)PE. Statistical analysis was done comparing categorical
      variables with Chi-square tests and frequencies of means via t-tests. Binary
      logistic regression analysis was performed to identify predictors of erosions,
      recurrence, malignancy and rheumatologic disorders. RESULTS: 331 cases of RS(3)PE
      were identified from 121 articles. RS(3)PE was found in older patients (71+/
      10.42 years) predominantly in males (n= 211, 63.36%), was symmetrical (n=297/311,
      95.50%) involved the hands (n=294/311, 94.53%) A concurrent rheumatologic
      condition was reported in 22 cases (6.65%), and malignancy in 54 cases (16.31%).
      Radiographic joint erosions were found in 5.5%. Most patients responded to medium
      dose glucocorticoids (16.12+/-9.5 mg/day). Patients with concurrent malignancy
      requiring non-significantly higher doses of prednisone (18.12 vs. 15.76 mg, p
      0.304) and higher likelihood of recurrence of disease (OR 4.04, 95% CI 1.10
      14.88, p=0.03). CONCLUSIONS: The symptoms and unique findings that make up
      RS(3)PE appear to represent a steroid-responsive disease that may be a harbinger
      of an underlying malignancy. More study is needed to understand the molecular
      origins of RS(3)PE in order to determine whether it is a separate disease
      process. Patients with concurrent cancer tend to have more severe presentations
      and higher rates of recurrence.

PMID- 27050251
TI  - The Effectiveness of hCG and LHRH in Boys with Cryptorchidism: A Meta-Analysis of
      Randomized Controlled Trials.
AB  - To systematically review the efficacy of hCG and LHRH on testicular descent in
      boys with cryptorchidism, comprehensive search was performed to identify
      randomized controlled trials (RCTs) in PubMed, EMBASE, the Cochrane Library,
      Wanfang Database, and China National Knowledge Infrastructure (CNKI) up to March
      2014. Outcomes included testicular complete descent rate (TCDR) and cure rate of
      patients. Study quality was evaluated using the Jadad scale. Meta-analysis was
      performed using Review Manager software. Finally, 13 studies were included. hCG
      and LHRH increased TCDR comparing with control group. The success rate of hCG and
      LHRH was 24 and 19%, respectively. Further, hCG and LHRH had significant effect
      on bilateral cryptorchidism, but not on unilateral cryptorchidism. All side
      effects were transitory and not severe, but if they have long-term harms were not
      clear. hCG and LHRH can effectively increase TCDR and there was no significant
      difference between them. However, the hormones cannot be recommended for everyone
      because of their low success rates and potential long-term harms. Further studies
      are needed to determine the efficacy of hormonal treatment for subtypes of
      cryptorchidism. 

PMID- 27050252
TI  - The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation,
      and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic
      Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - The current study was conducted to assess the effects of vitamin D-K-calcium co
      supplementation on endocrine, inflammation, and oxidative stress biomarkers in
      vitamin D-deficient women with polycystic ovary syndrome (PCOS). This randomized
      double-blind, placebo-controlled trial was performed on 60 vitamin D-deficient
      women diagnosed with PCOS aged 18-40 years old. Participants were randomly
      allocated into 2 groups to intake either 200 IU vitamin D, 90 MUg vitamin K plus,
      500 mg calcium supplements (n=30), or placebo (n=30) twice a day for 8 weeks.
      Endocrine, inflammation, and oxidative stress biomarkers were quantified at the
      beginning and the end of the study. After 8 weeks of intervention, compared with
      the placebo, vitamin D-K-calcium co-supplementation resulted in a significant
      reduction in serum-free testosterone (- 2.1+/-1.6 vs.+0.1+/-1.0 pg/ml, p<0.001)
      and dehydroepiandrosterone sulfate (DHEAS) levels (- 0.8+/-1.0 vs.-0.1+/-0.5
      MUg/ml, p=0.006). In addition, a significant increase in plasma total antioxidant
      capacity (TAC) (+ 75.7+/-126.1 vs.-80.4+/-242.8 mmol/l, p=0.005) and a
      significant difference in plasma malondialdehyde (MDA) concentrations (+ 0.03+/
      0.6 vs.+1.4+/-2.4 MUmol/l, p=0.005) was observed following the supplementation
      with vitamin D-K-calcium compared with the placebo. A trend toward a greater
      decrease in luteinizing hormone was observed in vitamin D-K-calcium co-supplement
      group compared to placebo group (- 7.0 vs.-1.2 IU/l, p=0.09). We did not find any
      significant effect of vitamin D-K-calcium co-supplementation on prolactin,
      follicle-stimulating hormone, 17-OH progesterone, inflammatory markers, and
      glutathione levels. Overall, vitamin D-K-calcium co-supplementation for 8 weeks
      among vitamin D-deficient women with PCOS had beneficial effects on serum DHEAS,
      free testosterone, plasma TAC, and MDA levels. 

PMID- 27050253
TI  - An Item Response Theory-Based, Computerized Adaptive Testing Version of the
      MacArthur-Bates Communicative Development Inventory: Words & Sentences (CDI:WS).
AB  - PURPOSE: This study investigated the feasibility and potential validity of an
      item response theory (IRT)-based computerized adaptive testing (CAT) version of
      the MacArthur-Bates Communicative Development Inventory: Words & Sentences
      (CDI:WS; Fenson et al., 2007) vocabulary checklist, with the objective of
      reducing length while maintaining measurement precision. METHOD: Parent-reported
      vocabulary for the American CDI:WS norming sample consisting of 1,461 children
      between the ages of 16 and 30 months was used to investigate the fit of the items
      to the 2-parameter logistic IRT model and to simulate CDI-CAT versions with 400,
      200, 100, 50, 25, 10, and 5 items. RESULTS: All but 14 items fit the 2-parameter
      logistic IRT model, and real data simulations of CDI-CATs with at least 50 items
      recovered full CDI scores with correlations over .95. Furthermore, the CDI-CATs
      with at least 50 items had similar correlations with age and socioeconomic status
      as the full CDI:WS. CONCLUSION: These results provide strong evidence that a CAT
      version of the CDI:WS has the potential to reduce length while maintaining the
      accuracy and precision of the full instrument.

PMID- 27050254
TI  - Association Between Hospital Characteristics and Performance on the New Hospital
      Acquired Condition Reduction Program's Surgical Site Infection Measures.

PMID- 27050255
TI  - Ammonium removal from high-strength aqueous solutions by Australian zeolite.
AB  - Removal of ammonium nitrogen (NH4(+)-N) particularly from sources which are
      highly rich in nitrogen is important for addressing environmental pollution.
      Zeolites, aluminosilicate minerals, are commonly used as commercial adsorbents
      and ion-exchange medium in number of commercial applications due to its high
      adsorption capacity of ammonium (NH4(+)). However, detailed investigations on
      NH4(+) adsorption and ion exchange capacities of Australian natural zeolites are
      rare, particularly under higher NH4(+) concentrations in the medium. Therefore,
      this study was conducted to determine NH4(+) adsorption characteristics of
      Australian natural zeolites at high NH4(+) concentrations with and without other
      chemical compounds in an aqueous solution. Results showed that initial NH4(+)
      concentration, temperature, reaction time, and pH of the solution had significant
      effects on NH4(+) adsorption capacity of zeolite. Increased retention time and
      temperature generally had a positive impact on adsorption. Freundlich model
      fitted well with adsorption process of Australian natural zeolites; however,
      Langmuir model had best fitted for the adsorption process of sodium (Na(+))
      treated zeolites. NaCl treatment increased the NH4(+) adsorption capacity of
      Australian zeolites by 25% at 1000 mg-N, NH4(+) solution. The maximum adsorption
      capacity of both natural Australian zeolites and Na(+) treated zeolites were
      estimated as 9.48 and 11.83 mg-N/g, respectively, which is lower than many
      zeolites from other sources. Compared to the NH4(+) only medium, presence of
      other competitive ions and acetic acid in the medium (resembling composition in
      digested swine manure slurries) reduced NH4(+) removal of natural and Na(+)
      treated zeolites by 44% and 57%, respectively. This suggests detailed
      investigations are required to determine practically achievable NH4(+) -N removal
      potential of zeolites for applications in complex mediums such as animal manure
      slurries. 

PMID- 27050256
TI  - DNA catabolites in triathletes: effects of supplementation with an aronia-citrus
      juice (polyphenols-rich juice).
AB  - In this study we analyzed whether our aronia-citrus juice (ACJ, the composition
      is based on a mixture of 95% citrus juice with 5% of Aronia melanocarpa juice),
      rich in polyphenols, and physical exercise had an effect on seven catabolites of
      DNA identified in plasma and on a urine isoprostane (8-iso-PGF2alpha). Sixteen
      elite triathletes on a controlled diet for triathlon training (45 days) were used
      in this clinical trial. Our results show a decrease in the 8-hydroxy-2'
      deoxyguanosine concentration due to chronic physical exercise. The ACJ intake and
      physical exercise maintained the guanosine-3',5'-cyclic monophosphate plasmatic
      concentrations and decreased the concentration of 8-hydroxyguanine as well as
      urinary values of 8-iso-PGF2alpha. Finally, we observed a significant increase in
      the 8-nitroguanosine levels in triathletes after ACJ intake, compared to the
      placebo stage. It is concluded that the combination of the intake of ACJ, rich in
      polyphenolic compounds, with adequate training was able to influence the
      plasmatic and urinary values of oxidative stress biomarkers. This suggests a
      positive effect on the oxidative damage and potential associations with DNA
      repair mechanisms. 

PMID- 27050257
TI  - Crystal structure of histone-like protein from Streptococcus mutans refined to
      1.9 A resolution.
AB  - Nucleoid-associated proteins (NAPs) in prokaryotes play an important
      architectural role in DNA bending, supercoiling and DNA compaction. In addition
      to architectural roles, some NAPs also play regulatory roles in DNA replication
      and repair, and act as global transcriptional regulators in many bacteria.
      Bacteria encode multiple NAPs and some of them are even essential for survival.
      Streptococcus mutans, a dental pathogen, encodes one such essential NAP called
      histone-like protein (HLP). Here, the three-dimensional structure of S. mutans
      HLP has been determined to 1.9 A resolution. The HLP structure is a dimer and
      shares a high degree of similarity with other bacterial NAPs, including HU. Since
      HLPs are essential for the survival of pathogenic streptococci, this structure
      determination is potentially beneficial for future drug development against these
      pathogens.

PMID- 27050258
TI  - Cloning, expression, purification and crystallization of Schizosaccharomyces
      pombe Set7, a putative histone methyltransferase.
AB  - Dysfunction of histone-modifying enzymes affects chromatin regulation and is
      involved in carcinogenesis, tumour progression and other diseases. Histone
      methyltransferases are a family of key histone-modifying enzymes, but their
      structures, functions and mechanisms are incompletely understood, thus
      constraining drug-design efforts. Here, preliminary steps towards structure
      function studies of Schizosaccharomyces pombe Set7, a putative histone
      methyltransferase and the first yeast full-length SET-domain-containing protein
      to be studied using X-ray crystallography, are reported. The methods from cloning
      to X-ray diffraction and phasing are discussed and the results will aid in
      prospective studies of histone-modifying enzymes.

PMID- 27050259
TI  - Crystal structure of the substrate-recognition domain of the Shigella E3 ligase
      IpaH9.8.
AB  - Infectious diseases caused by bacteria have significant impacts on global public
      health. During infection, pathogenic bacteria deliver a variety of virulence
      factors, called effectors, into host cells. The Shigella effector IpaH9.8
      functions as an ubiquitin ligase, ubiquitinating the NF-kappaB essential
      modulator (NEMO)/IKK-gamma to inhibit host inflammatory responses. IpaH9.8
      contains leucine-rich repeats (LRRs) involved in substrate recognition and an E3
      ligase domain. To elucidate the structural basis of the function of IpaH9.8, the
      crystal structure of the LRR domain of Shigella IpaH9.8 was determined and this
      structure was compared with the known structures of other IpaH family members.
      This model provides insights into the structural features involved in substrate
      specificity.

PMID- 27050260
TI  - Binding of Gd(3+) to the neuronal signalling protein calexcitin identifies an
      exchangeable Ca(2+)-binding site.
AB  - Calexcitin was first identified in the marine snail Hermissenda crassicornis as a
      neuronal-specific protein that becomes upregulated and phosphorylated in
      associative learning. Calexcitin possesses four EF-hand motifs, but only the
      first three (EF-1 to EF-3) are involved in binding metal ions. Past work has
      indicated that under physiological conditions EF-1 and EF-2 bind Mg(2+) and
      Ca(2+), while EF-3 is likely to bind only Ca(2+). The fourth EF-hand is
      nonfunctional owing to a lack of key metal-binding residues. The aim of this
      study was to use a crystallographic approach to determine which of the three
      metal-binding sites of calexcitin is most readily replaced by exogenous metal
      ions, potentially shedding light on which of the EF-hands play a 'sensory' role
      in neuronal calcium signalling. By co-crystallizing recombinant calexcitin with
      equimolar Gd(3+) in the presence of trace Ca(2+), EF-1 was shown to become fully
      occupied by Gd(3+) ions, while the other two sites remain fully occupied by
      Ca(2+). The structure of the Gd(3+)-calexcitin complex has been refined to an R
      factor of 21.5% and an Rfree of 30.4% at 2.2 A resolution. These findings suggest
      that EF-1 of calexcitin is the Ca(2+)-binding site with the lowest selectivity
      for Ca(2+), and the implications of this finding for calcium sensing in neuronal
      signalling pathways are discussed.

PMID- 27050261
TI  - Isolation, crystallization and crystal structure determination of bovine kidney
      Na(+),K(+)-ATPase.
AB  - Na(+),K(+)-ATPase is responsible for the transport of Na(+) and K(+) across the
      plasma membrane in animal cells, thereby sustaining vital electrochemical
      gradients that energize channels and secondary transporters. The crystal
      structure of Na(+),K(+)-ATPase has previously been elucidated using the enzyme
      from native sources such as porcine kidney and shark rectal gland. Here, the
      isolation, crystallization and first structure determination of bovine kidney
      Na(+),K(+)-ATPase in a high-affinity E2-BeF3(-)-ouabain complex with bound
      magnesium are described. Crystals belonging to the orthorhombic space group C2221
      with one molecule in the asymmetric unit exhibited anisotropic diffraction to a
      resolution of 3.7 A with full completeness to a resolution of 4.2 A. The
      structure was determined by molecular replacement, revealing unbiased electron
      density features for bound BeF3(-), ouabain and Mg(2+) ions.

PMID- 27050262
TI  - Crystal structure of a putative exo-beta-1,3-galactanase from Bifidobacterium
      bifidum S17.
AB  - Given the current interest in second-generation biofuels, carbohydrate-active
      enzymes have become the most important tool to overcome the structural
      recalcitrance of the plant cell wall. While some glycoside hydrolase families
      have been exhaustively described, others remain poorly characterized, especially
      with regard to structural information. The family 43 glycoside hydrolases are a
      diverse group of inverting enzymes; the available structure information on these
      enzymes is mainly from xylosidases and arabinofuranosidase. Currently, only one
      structure of an exo-beta-1,3-galactanase is available. Here, the production,
      crystallization and structure determination of a putative exo-beta-1,3
      galactanase from Bifidobacterium bifidum S17 (BbGal43A) are described. BbGal43A
      was successfully produced and showed activity towards synthetic galactosides.
      BbGal43A was subsequently crystallized and data were collected to 1.4 A
      resolution. The structure shows a single-domain molecule, differing from known
      homologues, and crystal contact analysis predicts the formation of a dimer in
      solution. Further biochemical studies are necessary to elucidate the differences
      between BbGal43A and its characterized homologues.

PMID- 27050263
TI  - Purification, crystallization and X-ray diffraction analysis of the DNA-binding
      domain of human heat-shock factor 2.
AB  - Cells respond to various proteotoxic stimuli and maintain protein homeostasis
      through a conserved mechanism called the heat-shock response, which is
      characterized by the enhanced synthesis of heat-shock proteins. This response is
      mediated by heat-shock factors (HSFs). Four genes encoding HSF1-HSF4 exist in the
      genome of mammals. In this protein family, HSF1 is the orthologue of the single
      HSF in lower eukaryotic organisms and is the major regulator of the heat-shock
      response, while HSF2, which shows low sequence homology to HSF1, serves as a
      developmental regulator. Increasing evidence has revealed biochemical properties
      and functional roles that are unique to HSF2, such as its DNA-binding preference
      and sumoylation patterns, which are distinct from those of HSF1. The structural
      basis for such differences, however, is poorly understood owing to the lack of
      available mammalian HSF structures. The N-terminal DNA-binding domain (DBD) is
      the most conserved functional module and is the only crystallizable domain in
      HSFs. To date, only HSF1 homologue structures from yeast and fruit fly have been
      determined. Along with extensive studies of the HSF family, more structural
      information, particularly from members with a remoter phylogenic relationship to
      the reported structures, e.g. HSF2, is needed in order to better understand the
      detailed mechanisms of HSF biology. In this work, the recombinant DBD (residues 7
      112) from human HSF2 was produced in Escherichia coli and crystallized. An X-ray
      diffraction data set was collected to 1.32 A resolution from a crystal belonging
      to space group P212121 with unit cell-parameters a = 65.66, b = 67.26, c = 93.25
      A. The data-evaluation statistics revealed good quality of the collected data,
      thus establishing a solid basis for the determination of the first structure at
      atomic resolution in this protein family.

PMID- 27050264
TI  - Crystal structures of Leishmania mexicana arginase complexed with alpha,alpha
      disubstituted boronic amino-acid inhibitors.
AB  - Leishmania arginase is a potential drug target for the treatment of leishmaniasis
      because this binuclear manganese metalloenzyme initiates de novo polyamine
      biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine
      and urea. The product L-ornithine subsequently undergoes decarboxylation to yield
      putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines
      such as spermidine are essential for the growth and survival of the parasite, so
      inhibition of enzymes in the polyamine-biosynthetic pathway comprises an
      effective strategy for treating parasitic infections. To this end, two X-ray
      crystal structures of L. mexicana arginase complexed with alpha,alpha
      disubstituted boronic amino-acid inhibitors based on the molecular scaffold of 2
      (S)-amino-6-boronohexanoic acid are now reported. Structural comparisons with
      human and parasitic arginase complexes reveal interesting differences in the
      binding modes of the additional alpha-substituents, i.e. the D side chains, of
      these inhibitors. Subtle differences in the three-dimensional contours of the
      outer active-site rims among arginases from different species lead to different
      conformations of the D side chains and thus different inhibitor-affinity trends.
      The structures suggest that it is possible to maintain affinity while fine-tuning
      intermolecular interactions of the D side chain of alpha,alpha-disubstituted
      boronic amino-acid inhibitors in the search for isozyme-specific and species
      specific arginase inhibitors.

PMID- 27050265
TI  - A novel microseeding method for the crystallization of membrane proteins in
      lipidic cubic phase.
AB  - Random microseed matrix screening (rMMS), in which seed crystals are added to
      random crystallization screens, is an important breakthrough in soluble protein
      crystallization that increases the number of crystallization hits that are
      available for optimization. This greatly increases the number of soluble protein
      structures generated every year by typical structural biology laboratories.
      Inspired by this success, rMMS has been adapted to the crystallization of
      membrane proteins, making LCP seed stock by scaling up LCP crystallization
      conditions without changing the physical and chemical parameters that are
      critical for crystallization. Seed crystals are grown directly in LCP and, as
      with conventional rMMS, a seeding experiment is combined with an additive
      experiment. The new method was used with the bacterial integral membrane protein
      OmpF, and it was found that it increased the number of crystallization hits by
      almost an order of magnitude: without microseeding one new hit was found, whereas
      with LCP-rMMS eight new hits were found. It is anticipated that this new method
      will lead to better diffracting crystals of membrane proteins. A method of
      generating seed gradients, which allows the LCP seed stock to be diluted and the
      number of crystals in each LCP bolus to be reduced, if required for optimization,
      is also demonstrated.

PMID- 27050266
TI  - Applications of thin-film sandwich crystallization platforms.
AB  - Examples are shown of protein crystallization in, and data collection from,
      solutions sandwiched between thin polymer films using vapour-diffusion and batch
      methods. The crystallization platform is optimal for both visualization and in
      situ data collection, with the need for traditional harvesting being eliminated.
      In wells constructed from the thinnest plastic and with a minimum of aqueous
      liquid, flash-cooling to 100 K is possible without significant ice formation and
      without any degradation in crystal quality. The approach is simple; it utilizes
      low-cost consumables but yields high-quality data with minimal sample
      intervention and, with the very low levels of background X-ray scatter that are
      observed, is optimal for microcrystals.

PMID- 27050267
TI  - Crystal structure of a tankyrase 1-telomere repeat factor 1 complex.
AB  - Telomere repeat factor 1 (TRF1) is a subunit of shelterin (also known as the
      telosome) and plays a critical role in inhibiting telomere elongation by
      telomerase. Tankyrase 1 (TNKS1) is a poly(ADP-ribose) polymerase that regulates
      the activity of TRF1 through poly(ADP-ribosyl)ation (PARylation). PARylation of
      TRF1 by TNKS1 leads to the release of TRF1 from telomeres and allows telomerase
      to access telomeres. The interaction between TRF1 and TNKS1 is thus important for
      telomere stability and the mitotic cell cycle. Here, the crystal structure of a
      complex between the N-terminal acidic domain of TRF1 (residues 1-55) and a
      fragment of TNKS1 covering the second and third ankyrin-repeat clusters (ARC2-3)
      is presented at 2.2 A resolution. The TNKS1-TRF1 complex crystals were optimized
      using an 'oriented rescreening' strategy, in which the initial crystallization
      condition was used as a guide for a second round of large-scale sparse-matrix
      screening. This crystallographic and biochemical analysis provides a better
      understanding of the TRF1-TNKS1 interaction and the three-dimensional structure
      of the ankyrin-repeat domain of TNKS.

PMID- 27050268
TI  - Crystal structure of CotA laccase complexed with 2,2-azinobis-(3
      ethylbenzothiazoline-6-sulfonate) at a novel binding site.
AB  - The CotA laccase from Bacillus subtilis is an abundant component of the spore
      outer coat and has been characterized as a typical laccase. The crystal structure
      of CotA complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS)
      in a hole motif has been solved. The novel binding site was about 26 A away from
      the T1 binding pocket. Comparison with known structures of other laccases
      revealed that the hole is a specific feature of CotA. The key residues Arg476 and
      Ser360 were directly bound to ABTS. Site-directed mutagenesis studies revealed
      that the residues Arg146, Arg429 and Arg476, which are located at the bottom of
      the novel binding site, are essential for the oxidation of ABTS and
      syringaldazine. Specially, a Thr480Phe variant was identified to be almost 3.5
      times more specific for ABTS than for syringaldazine compared with the wild type.
      These results suggest this novel binding site for ABTS could be a potential
      target for protein engineering of CotA laccases.

PMID- 27050269
TI  - Errors in Crystal structure of HINT from Helicobacter pylori.
AB  - Inaccuracies in the article, Crystal structure of HINT from Helicobacter pylori
      by Tarique et al. [(2016) Acta Cryst. F72, 42-48] are presented, and a brief
      history of HINT nomenclature is discussed. 

PMID- 27050270
TI  - Response to Errors in Crystal structure of HINT from Helicobacter pylori.
AB  - A response is published to a Letter to the Editor by Maize [(2016), Acta Cryst.
      F72, 336-337]. 

PMID- 27050272
TI  - Epidermal Nbn deletion causes premature hair loss and a phenotype resembling
      psoriasiform dermatitis.
AB  - Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report
      a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair
      follicle (HF) progenitors promoted increased DNA damage signaling, stimulating
      p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF
      growth arrest and hair loss. At later stages, the basal keratinocytes layer
      exhibited also enhanced DNA damage response but in contrast to the one in HF
      progenitor was not associated with pro-inflammatory cytokines expression, but
      rather increased proliferation, lack of differentiation and immune response
      resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation
      significantly exacerbated this phenotype, due to the lack of inhibition of pro
      inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel
      functions of Nbn in HF maintenance and prevention of skin inflammation and we
      provide a mechanistic explanation that links cell intrinsic DNA maintenance with
      large scale morphological tissue alterations. 

PMID- 27050271
TI  - Comprehensive analysis of the transcriptional profile of the Mediator complex
      across human cancer types.
AB  - The Mediator complex is a key regulator of gene transcription and several studies
      demonstrated altered expressions of particular subunits in diverse human
      diseases, especially cancer. However a systematic study deciphering the
      transcriptional expression of the Mediator across different cancer entities is
      still lacking.We therefore performed a comprehensive in silico cancer vs. benign
      analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using
      Oncomine datasets. The transcriptional expression profiles across almost all
      cancer entities showed differentially expressed MEDs as compared to benign
      tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12
      in lung cancer (LCa) were validated and further investigated by
      immunohistochemical staining on tissue microarrays containing large numbers of
      specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and
      advanced TNM stage and showed higher expression in metastatic than primary
      tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired
      proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to
      serve as a novel therapeutic target in ccRCC. Taken together, our Mediator
      complex transcriptome proved to be a valid tool for identifying cancer-related
      shifts in Mediator complex composition, revealing that MEDs do exhibit cancer
      specific transcriptional expression profiles. 

PMID- 27050273
TI  - Apoptosis signal-regulating kinase 1 mediates the inhibitory effect of hepatocyte
      nuclear factor-4alpha on hepatocellular carcinoma.
AB  - Previous studies provided substantial evidence of a striking suppressive effect
      of hepatocyte nuclear factor 4alpha (HNF4alpha) on hepatocellular carcinoma
      (HCC). Apoptosis signal-regulating kinase 1 (ASK1) is involved in death receptor
      mediated apoptosis and may acts as a tumor suppressor in hepatocarcinogenesis.
      However, the status and function of ASK1 during HCC progression are unclear. In
      this study, we found that HNF4alpha increased ASK1 expression by directly binding
      to its promoter. ASK1 expression was dramatically suppressed and correlated with
      HNF4alpha levels in HCC tissues. Reduced ASK1 expression was associated with
      aggressive tumors and poor prognosis for human HCC. Moreover, ASK1 inhibited the
      malignant phenotype of HCC cells in vitro. Intratumoral ASK1 injection
      significantly suppressed the growth of subcutaneous HCC xenografts in nude mice.
      More interestingly, systemic ASK1 delivery strikingly inhibited the growth of
      orthotopic HCC nodules in NOD/SCID mice. In addition, inhibition of endogenous
      ASK1 partially reversed the suppressive effects of HNF4alpha on HCC.
      Collectively, this study highlights the suppressive effect of ASK1 on HCC and its
      biological significance in HCC development. These outcomes broaden the knowledge
      of ASK1 function in HCC progression, and provide a novel potential prognostic
      biomarker and therapeutic target for advanced HCC. 

PMID- 27050274
TI  - MicroRNA-31 functions as a tumor suppressor and increases sensitivity to
      mitomycin-C in urothelial bladder cancer by targeting integrin alpha5.
AB  - Urothelial bladder cancer (UBC) is a common genitourinary malignancy. MiR-31, a
      well-identified miRNA, exhibits diverse properties in different cancers. However,
      the specific functions and mechanisms of miR-31 in UBC have not been
      investigated. In this study, tumor samples, especially invasive UBC, showed
      significantly reduced level of miR-31, as compared with normal urothelium.
      Prognostic analysis using the EORTC model showed that down-regulation of miR-31
      correlated with higher risks of recurrence and progression in noninvasive UBC
      cases. Remarkably, overexpression of miR-31 mimics in UBC cell lines inhibited
      cell proliferation, migration and invasion. Integrin alpha5 (ITGA5), an integrin
      family member, was subsequently identified as a direct target of miR-31 in UBC
      cells. When treated with mitomycin-C (MMC), miR-31-expressing UBC cells displayed
      lower survival and higher apoptotic rates, and deactivated Akt and ERK. These
      effects arising from miR-31 overexpression were abrogated by ITGA5 restoration.
      Furthermore, miR-31 markedly inhibited tumor growth and increased the
      effectiveness of MMC in UBC xenografts. In summary, our data suggest that miR-31
      is a prognostic predictor and can serve as a potential therapeutic target of UBC.

PMID- 27050275
TI  - Post-treatment serum lactic dehydrogenase as a predictive indicator for distant
      metastasis and survival of patients with nasopharyngeal carcinoma.
AB  - PURPOSE: To examine the function of serum lactic dehydrogenase (SLDH) level after
      intensity-modulated radiotherapy (IMRT) as a predictive factor for and loco
      regional relapse free survival (LRFS), distant metastasis-free survival (DMFS),
      disease free survival (DFS), and overall survival(OS) among patients with in-situ
      nasopharyngeal carcinoma (NPC). RESULTS: Compared with the normal pt-SLDH group,
      elevated pt-SLDH demonstrated significant lower DMFS (46 versus 66 months, hazard
      ratio (HR) 4.07, 95% CI 2.43-6.80, p < 0.001), DFS (46 versus 63 months, HR 2.78,
      95% CI 1.70-4.53, p < 0.001), and OS (54 versus 66 months, HR 2.93, 95% CI 1.65
      5.23, p < 0.001). Distant metastasis were observed in 32.8% (20/61) patients with
      elevated pt-SLDH, and 8% (54/678) in normal SLDH (odds ratio (OR) 6.13, 95% CI
      3.35-11.18, p < 0.001). COX regression showed that pt-SLDH was an independent
      prognostic factors for OS (HR 2.91, 95% CI 1.57-5.41, p < 0.001), DMFS (HR 4.21,
      95% CI 2.51-7.07, p < 0.001), LRFS (HR 2.53, 95% CI 1.22-5.24, p < 0.001), and
      DFS (HR 2.81, 95% CI 1.72-4.59, p < 0.001). MATERIALS AND METHODS: The records of
      739 in-situ NPC patients admitted to Zhejiang Cancer Hospital between January
      2007 and May 2012 were retrospectively reviewed. The relationships between post
      treatment SLDH (pt-SLDH) and LRFS, DMFS, DFS, and OS were analyzed. CONCLUSIONS:
      Our finding indicated that elevated pt-SLDH could be a simple available
      prognostic indicator for distant metastasis and survival for in-situ NPC
      patients.

PMID- 27050277
TI  - Migration-inducing gene 7 promotes tumorigenesis and angiogenesis and
      independently predicts poor prognosis of epithelial ovarian cancer.
AB  - Epithelial ovarian carcinomas (EOC) cause more mortality than any other cancer of
      the female reproductive system. New therapeutic approaches to reduce EOC
      mortality have been largely unsuccessful due to the poor understanding of the
      mechanisms underlying EOC proliferation and metastasis. Progress in EOC treatment
      is further hampered by a lack of reliable prognostic biomarkers for early risk
      assessment. In this study, we identify that Migration-Inducting Gene 7 (MIG-7) is
      specifically induced in human EOC tissues but not normal ovaries or ovarian cyst.
      Ovarian MIG-7 expression strongly correlated with EOC progression. Elevated MIG-7
      level at the time of primary cytoreductive surgery was a strong and independent
      predictor of poor survival of EOC patients. Cell and murine xenograft models
      showed that MIG-7 was required for EOC proliferation and invasion, and MIG-7
      enhanced EOC-associated angiogenesis by promoting the expression of vascular
      endothelial growth factor. Inhibiting MIG-7 by RNA interference in grafted EOC
      cells retarded tumor growth, angiogenesis and improved host survival, and
      suppressing MIG-7 expression with a small molecule inhibitor D-39 identified from
      the medicinal plant Liriope muscari mitigated EOC growth and invasion and
      specifically abrogated the expression of vascular endothelial growth factor. Our
      data not only reveal a critical function of MIG-7 in EOC growth and metastasis
      and support MIG-7 as an independent prognostic biomarker for EOC, but also
      demonstrate that therapeutic targeting of MIG-7 is likely beneficial in the
      treatment of EOC. 

PMID- 27050276
TI  - Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and
      p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R
      pathway inhibitor.
AB  - The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is
      aberrantly activated in multiple cancers and can promote proliferation and
      chemotherapy resistance. Multiple IGF-1R inhibitors have been developed as
      potential therapeutics. However, these inhibitors have failed to increase patient
      survival when given alone or in combination with chemotherapy agents. The
      reason(s) for the disappointing clinical effect of these inhibitors is not fully
      understood. Cisplatin (CP) activated the IGF-1R/AKT/mTORC1 pathway and stabilized
      p53 in osteosarcoma (OS) cells. p53 knockdown reduced IGF-1R/AKT/mTORC1
      activation by CP, and IGF-1R inhibition reduced the accumulation of p53. These
      data demonstrate positive crosstalk between p53 and the IGF-1R/AKT/mTORC1 pathway
      in response to CP. Further studies showed the effect of IGF-1R inhibition on CP
      response is dependent on p53 status. In p53 wild-type cells treated with CP, IGF
      1R inhibition increased p53s apoptotic function but reduced p53-dependent
      senescence, and had no effect on long term survival. In contrast, in p53
      null/knockdown cells, IGF-1R inhibition reduced apoptosis in response to CP and
      increased long term survival. These effects were due to p27 since IGF-1R
      inhibition stabilized p27 in CP-treated cells, and p27 depletion restored
      apoptosis and reduced long term survival. Together, the results demonstrate 1)
      p53 expression determines the effect of IGF-1R inhibition on cancer cell CP
      response, and 2) crosstalk between the IGF-1R/AKT/mTORC1 pathway and p53 and p27
      can reduce cancer cell responsiveness to chemotherapy and may ultimately limit
      the effectiveness of IGF-1R pathway inhibitors in the clinic. 

PMID- 27050278
TI  - Lung cancer-derived galectin-1 contributes to cancer associated fibroblast
      mediated cancer progression and immune suppression through TDO2/kynurenine axis.
AB  - Communication between cancer cells and their microenvironment plays an important
      role in cancer development, but the precise mechanisms by which cancer-associated
      fibroblasts (CAF) impact anti-cancer immunity and cancer progression in lung
      cancer are poorly understood. Here, we report that lung fibroblasts when
      activated by lung cancer cells produce tryptophan metabolite kynurenine (Kyn)
      that inhibits dendritic cells' differentiation and induces cancer growth as well
      as migration. We identified TDO2 (tryptophan 2,3-dioxygenase) as the main enzyme
      expressed in fibroblasts capable of tryptophan metabolism. Mechanistically,
      condition medium of CAF or exogenous kynurenine stimulated AKT, with no lysine 1
      (WNK1) and cAMP response element-bindingprotein (CREB) phosphorylation in lung
      cancer cells. Inhibition of the AKT/CREB pathway prevents cancer proliferation,
      while inhibition of the AKT/ WNK1 reverted epithelial-to-mesenchymal transition
      and cancer migration induced by kynurenine. Moreover, we also demonstrate that
      lung cancer-derived galectin-1 contributes to the upregulation of TDO2 in CAF
      through an AKT-dependent pathway. Immunohistochemical analysis of lung cancer
      surgical specimens revealed increased TDO2 expression in the fibroblasts adjacent
      to the cancer. Furthermore, in vivo studies showed that administration of TDO2
      inhibitor significantly improves DCs function and T cell response, and decreases
      tumor metastasis in mice. Taken together, our data identify the feedback loop,
      consisting of cancer-derived galectin-1 and CAF-producing kynurenine, that
      sustains lung cancer progression. These findings suggest that targeting this
      pathway may be a promising therapeutic strategy. 

PMID- 27050279
TI  - Activation of epithelial proliferation induced by Eimeria acervulina infection in
      the duodenum may be associated with cholesterol metabolism.
AB  - Cell proliferation in the intestine is commonly occurred during infection and
      inflammation to replace damaged enterocytes, and cholesterol as an essential
      constituent of cell membrane, is required for cell proliferation and growth. Here
      we found that coccidium-challenged (CC) chickens showed severe damages in
      intestinal structure, a significant increase of cell proliferation, and an
      activation of genes expression involved in the innate immune response. Compared
      to control (CON), CC chickens showed a marked decrease of cholesterol (Tch) level
      in the circulating system, but a significant increase in local duodenum
      epithelium. Increase of LDLR protein combined with a significant decrease of
      CYP27A1 protein expression in duodenum epithelium may contribute to intestinal
      cholesterol accumulation in CC chickens. Moreover, we found miRNAs targeting to
      CYP27A1 gene participating in post-transcriptional regulation. Hence, these
      results provide a new insight for the intervention of epithelial proliferation
      and cholesterol metabolism in the gastrointestinal tracts. 

PMID- 27050280
TI  - Single-nucleotide polymorphisms in PSCA and the risk of breast cancer in a
      Chinese population.
AB  - This study explored the associations between common PSCA single-nucleotide
      polymorphisms (rs2294008, rs2978974, and rs2976392) and breast cancer among 560
      breast cancer cases and 583 controls (Chinese Han women). We found rs2294008 was
      significantly associated with a high risk of breast cancer (homozygote model,
      odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.06-2.59; recessive, OR:
      1.64, 95% CI: 1.06-2.53). And stratification by menopausal status revealed an
      association of the minor allele of rs2294008 with breast cancer risk among
      premenopausal (homozygote model, OR: 2.41, 95% CI: 1.03-5.66; recessive, OR:
      2.80, 95 % CI: 1.21-6.47) and postmenopausal women (allele model, OR: 1.29, 95%
      CI: 1.01-1.65). Rs2978974 influenced the breast cancer risk among postmenopausal
      women in heterozygote model (OR: 1.47, 95% CI: 1.05-2.07). When stratified by
      clinicopathologic features, the T allele of rs2294008 was associated with
      progesterone receptor status (homozygote model, OR: 1.98, 95% CI: 1.08-3.63;
      recessive, OR: 1.87, 95% CI: 1.04-3.37), and the rs2976392 polymorphism was
      associated with high lymph node metastasis risk in homozygote model (OR: 2.09,
      95%CI: 1.01-4.31). Further haplotype analysis suggested that Trs2294008
      Ars2976392 Grs2978974 haplotype enhances breast cancer risk (OR:1.52, 95%CI:1.23
      1.89, P<0.001). Therefore, among Chinese Han women, the PSCA rs2294008,
      rs2978974, and rs2976392 minor alleles are associated with increased breast
      cancer risk especially in progesterone receptor positive breast cancer patients,
      with breast cancer risk in postmenopausal women, and with high lymph node
      metastasis risk, respectively. Moreover, Trs2294008 Ars2976392 Grs2978974
      haplotype was associated with significantly increased risk of breast cancer. 

PMID- 27050281
TI  - CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through
      abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating
      mitochondrial apoptotic pathway.
AB  - The mammalian target of rapamycin (mTOR) is a potentially important therapeutic
      target in a broad range of cancer types. mTOR inhibitors such as rapamycin and
      its analogs (rapalogs) have been proven effective as anticancer agents in non
      small cell lung cancer (NSCLC), whereas they strongly enhance phosphorylation of
      eukaryotic translation initiation factor 4E (eIF4E) and activation of Akt, which
      cause resistance to mTOR-targeted therapy after an initial response. Rapamycin
      induces eIF4E phosphorylation by activating MAPK-interacting kinases (Mnks), and
      therefore targeting Mnk/eIF4E pathway represents a potential therapeutic strategy
      for the treatment of NSCLC. Here, our results showed that over-expression of p
      Mnk1 and p-eIF4E was significantly associated with poor overall survival of NSCLC
      patients and high expression of p-Mnk1 might act as an independent prognostic
      biomarker for these patients. Meanwhile, inhibiting Mnk1 expression by Mnk
      inhibitor (CGP57380) could abrogate rapalogs (RAD001)-induced eIF4E
      phosphorylation and Akt activation. Furthermore, combination of CGP57380 and
      RAD001 could induce NSCLC cells apoptosis via activating intrinsic mitochondrial
      pathway, and exert synergistic antitumor efficacy both in vitro and in vivo. In
      conclusion, combination of targeting both mTOR and Mnk/eIF4E signaling pathways
      to enhance effectiveness of mTOR-targeted cancer therapy might be significant
      innovation for the personalized treatment of NSCLC. 

PMID- 27050282
TI  - Lessons learned from a SIRT2-selective inhibitor.

PMID- 27050283
TI  - Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the
      peripheral blood of Hodgkin and non-Hodgkin lymphoma patients.
AB  - Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described
      as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify
      with mononuclear cells after density gradient centrifugation of blood from cancer
      patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL)
      remains unclear.The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells
      were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy
      donors (n = 48). The immunosuppressive functions of these cells were tested in
      vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient
      clinicopathological features and outcome, were evaluated.CD66b+CD33dimHLA-DR
      cells were increased in PBMCs from HL and B-cell NHL patients as compared to
      healthy donors: 2.18 (0.02-70.92) vs 0.42 (0.04-2.97), p < 0.0001. Their
      percentage remained significantly higher even considering HL (n = 31), indolent
      (n = 31) and aggressive (n = 62) B-cell NHL patients separately: 1.54 (0.28
      26.34), 2.15 (0.02-20.08), and 2.96 (0.25-70.92), respectively, p < 0.0001.
      CD66b+CD33dimHLA-DR-cells in patient PBMCs were mostly composed of mature
      CD11b+CD16+ low-density neutrophils in an activated status, as revealed by their
      higher CD11b and CD66b expression as compared to conventionally isolated (normal
      density) autologous or healthy donor neutrophils. The in vitro depletion of
      CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells.
      Higher frequencies of CD66b+CD33dimHLA-DR- G-MDSCs correlated significantly with
      unfavorable prognostic index scores and a shorter freedom from disease
      progression.PBMCs from HL and B-cell NHL patients contain a population of
      CD66b+CD33dimHLA-DR- G-MDSCs, mostly composed of activated low-density
      neutrophils with immunosuppressive properties. These findings disclose a
      previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas,
      therefore anticipating possible targets for therapeutic interventions. 

PMID- 27050284
TI  - Repressor and activator protein accelerates hepatic ischemia reperfusion injury
      by promoting neutrophil inflammatory response.
AB  - Repressor and activator protein (Rap1) directly regulates nuclear factor-kappaB
      (NF-kappaB) dependent signaling, which contributes to hepatic IRI. We here
      intended to investigate the effect of Rap1 in hepatic ischemia reperfusion injury
      (IRI) and to explore the underlying mechanisms. The association of Rap1
      expression with hepatic inflammatory response were investigated in both human and
      rat liver transplantation. The effect of Rap1 in hepatic IRI was studied in Rap1
      knockout mice IRI model in vivo and primary cells in vitro. Our results showed
      that over expression of Rap1 was associated with severe liver graft inflammatory
      response, especially in living donor liver transplantation. The results were also
      validated in rat liver transplantation model. In mice hepatic IRI model, the
      knockout of Rap1 reduced hepatic damage and hepatic inflammatory response. In
      primary cells, the knockout of Rap1 suppressed neutrophils migration activity and
      adhesion in response to liver sinusoidal endothelial cells through down
      regulating neutrophils F-Actin expression and CXCL2/CXCR2 pathway. In addition,
      the knockout of Rap1 also decreased production of pro-inflammatory
      cytokines/chemokines in primary neutrophils and neutrophils-induced hepatocyte
      damage. In conclusion, Rap1 may induce hepatic IRI through promoting neutrophils
      inflammatory response. Rap1 may be the potential therapeutic target of
      attenuating hepatic IRI. 

PMID- 27050285
TI  - Antioxidant Responses in Relation to Persistent Organic Pollutants and Metals in
      a Low- and a High-Exposure Population of Seabirds.
AB  - Oxidative stress occurs when there is an imbalance between the production of
      reactive oxygen species (ROS) and antioxidant defense. Exposure to pollutants may
      increase ROS and affect antioxidant levels, and the resulting oxidative stress
      may negatively affect both reproduction and survival. We measured concentrations
      of 18 persistent organic pollutants (POPs) and 9 toxic elements in blood, as well
      as total antioxidant capacity (TAC), total glutathione (tGSH), and carotenoids in
      plasma of Baltic and Arctic female common eiders (Somateria mollissima) (N = 54)
      at the end of their incubation-related fasting. The more polluted Baltic
      population had higher TAC and tGSH concentrations compared to the Arctic
      population. Carotenoid levels did not differ between populations. The effect of
      mixtures of pollutants on the antioxidants was assessed, and the summed molar
      blood concentrations of 14 POPs were positively related to TAC. There was no
      significant relationship between the analyzed pollutants and tGSH concentrations.
      The adaptive improvement of the antioxidant defense system in the Baltic
      population may be a consequence of increased oxidative stress. However, both
      increased oxidative stress and energy allocation toward antioxidant defense may
      have adverse consequences for Baltic eiders at the incubation stage, when energy
      resources reach an annual minimum due to incubation-related fasting.

PMID- 27050286
TI  - Coagulation monitoring in postcardiotomy ECMO: conventional tests, point-of-care,
      or both?
AB  - BACKGROUND: The aim of this study was to assess the association of the
      coagulation point-of-care (POC) tests activated clotting time (ACT) and
      thromboelastography-derived parameters reaction time (R-time) and maximum
      amplitude (MA) with the standard coagulation tests during postcardiotomy
      extracorporeal membrane oxygenation (ECMO), finding adequate values predictive
      for the target range of the standard coagulation tests. METHODS: Thirty-one
      patients undergoing postcardiotomy ECMO with heparin anticoagulation were
      analyzed. Paired data of the POC tests and standard coagulation tests were
      analyzed for association and positive predictive value (PPV). RESULTS: The
      following target range values for standard coagulation test were settled:
      activated partial thromboplastin time (aPTT) 50-70 seconds; international
      normalized ratio (INR) 1.5-2.5; platelet count >50,000 cells/uL; fibrinogen >150
      mg/dL. The best predictor for the desired aPTT range was an ACT of 162-185
      seconds. A combination of an ACT<162 seconds with an R-time <10 minutes had an
      83% PPV for a short aPTT. A combination of an ACT>185 seconds with an R-time >27
      minutes had a 71% PPV for a long aPTT. No predictive ability of the POC tests was
      found in terms of the optimal INR range. An MA value <41 mm had a 75% PPV for a
      low platelet count or fibrinogen level. CONCLUSIONS: Diagnostic-therapeutic
      algorithms based on coagulation POC-tests may be useful to manage anticoagulation
      during postcardiotomy ECMO. The best PPV for prompting therapeutic decision is
      provided by a combination of ACT and visco-elastic tests.

PMID- 27050287
TI  - Reactive Oxygen Species and Neutrophil Function.
AB  - Neutrophils are essential for killing bacteria and other microorganisms, and they
      also have a significant role in regulating the inflammatory response. Stimulated
      neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of
      superoxide, which acts as a precursor of hydrogen peroxide and other reactive
      oxygen species that are generated by their heme enzyme myeloperoxidase. When
      neutrophils engulf bacteria they enclose them in small vesicles (phagosomes) into
      which superoxide is released by activated NOX2 on the internalized neutrophil
      membrane. The superoxide dismutates to hydrogen peroxide, which is used by
      myeloperoxidase to generate other oxidants, including the highly microbicidal
      species hypochlorous acid. NOX activation occurs at other sites in the cell,
      where it is considered to have a regulatory function. Neutrophils also release
      oxidants, which can modify extracellular targets and affect the function of
      neighboring cells. We discuss the identity and chemical properties of the
      specific oxidants produced by neutrophils in different situations, and what is
      known about oxidative mechanisms of microbial killing, inflammatory tissue
      damage, and signaling. 

PMID- 27050288
TI  - Cellular Homeostasis and Aging.
AB  - Aging and longevity are controlled by a multiplicity of molecular and cellular
      signaling events that interface with environmental factors to maintain cellular
      homeostasis. Modulation of these pathways to extend life span, including insulin
      like signaling and the response to dietary restriction, identified the cellular
      machineries and networks of protein homeostasis (proteostasis) and stress
      resistance pathways as critical players in the aging process. A decline of
      proteostasis capacity during aging leads to dysfunction of specific cell types
      and tissues, rendering the organism susceptible to a range of chronic diseases.
      This volume of the Annual Review of Biochemistry contains a set of two reviews
      addressing our current understanding of the molecular mechanisms underlying aging
      in model organisms and humans. 

PMID- 27050289
TI  - New Fusaric Acid Derivatives from the Endophytic Fungus Fusarium oxysporum and
      Their Phytotoxicity to Barley Leaves.
AB  - Chemical investigation of the endophytic fungus Fusarium oxysporum isolated from
      fruits of Drepanocarpus lunatus afforded eight new fusaric acid derivatives,
      fusaricates A-G, 1-7, and 10-hydroxy-11-chlorofusaric acid, 8, along with four
      known compounds. Their structures were elucidated by one- and two-dimensional NMR
      as well as MS data and by comparison with the literature. The absolute
      configurations of fusaricates C-E, 3-5, were determined using chiral GC-MS.
      Fusaricates A-G, 1-7, represent the first examples of fusaric acid linked to a
      polyalcohol moiety via an ester bond. All isolated fusaric acid derivatives 1-8
      showed significant phytotoxicity to leaves of barley. 

PMID- 27050290
TI  - Characterizing anomalous diffusion in crowded polymer solutions and gels over
      five decades in time with variable-lengthscale fluorescence correlation
      spectroscopy.
AB  - The diffusion of macromolecules in cells and in complex fluids is often found to
      deviate from simple Fickian diffusion. One explanation offered for this behavior
      is that molecular crowding renders diffusion anomalous, where the mean-squared
      displacement of the particles scales as <r(2)>?t(alpha) with alpha < 1.
      Unfortunately, methods such as fluorescence correlation spectroscopy (FCS) or
      fluorescence recovery after photobleaching (FRAP) probe diffusion only over a
      narrow range of lengthscales and cannot directly test the dependence of the mean
      squared displacement (MSD) on time. Here we show that variable-lengthscale FCS
      (VLS-FCS), where the volume of observation is varied over several orders of
      magnitude, combined with a numerical inversion procedure of the correlation data,
      allows retrieving the MSD for up to five decades in time, bridging the gap
      between diffusion experiments performed at different lengthscales. In addition,
      we show that VLS-FCS provides a way to assess whether the propagator associated
      with the diffusion is Gaussian or non-Gaussian. We used VLS-FCS to investigate
      two systems where anomalous diffusion had been previously reported. In the case
      of dense cross-linked agarose gels, the measured MSD confirmed that the diffusion
      of small beads was anomalous at short lengthscales, with a cross-over to simple
      diffusion around ~1 MUm, consistent with a caged diffusion process. On the other
      hand, for solutions crowded with marginally entangled dextran molecules, we
      uncovered an apparent discrepancy between the MSD, found to be linear, and the
      propagators at short lengthscales, found to be non-Gaussian. These contradicting
      features call to mind the "anomalous, yet Brownian" diffusion observed in several
      biological systems, and the recently proposed "diffusing diffusivity" model.

PMID- 27050291
TI  - Metal-assisted addition of a nitrate anion to bis(oxy)enamines. A general
      approach to the synthesis of alpha-nitroxy-oxime derivatives from nitronates.
AB  - The synthesis of alpha-nitroxy-substituted oxime derivatives has been achieved by
      an unprecedented metal-assisted addition of a nitrate anion to bis(oxy)enamines,
      which are readily available from nitronates or nitroalkanes. The method has a
      broad scope and provides access to alpha-nitroxy-oximes and their cyclic ethers
      including nitroxy-substituted isoxazolines and dihydro-1,2-oxazines, which are of
      interest as potential NO-donors and intermediates in the synthesis of bioactive
      molecules. 

PMID- 27050292
TI  - Is the risk for sexually transmissible infections (STI) lower among women with
      exclusively female sexual partners compared with women with male partners? A
      retrospective study based on attendees at a Norwegian STI clinic from 2004 to
      2014.
AB  - BACKGROUND: The prevalence of and the risk for sexually transmissible infections
      (STIs) for women engaging in same-sex sexual behaviour was investigated among
      women attending an STI clinic. METHODS: Data from electronic medical records were
      reviewed and logistic regression used to estimate the odds ratio (OR) of STIs.
      Women reporting life-time exclusively female partners (WSW) and women reporting
      female and male partners (WSWM) were compared with women reporting exclusively
      male partners (WSM). Outcomes included: Chlamydia trachomatis, Mycoplasma
      genitalium, Neisseria gonorrhoea, HIV and syphilis. RESULTS: The study population
      comprised 103564 women (WSW 641, WSWM 12010 and WSM 90913). Overall prevalence of
      STIs was 8%. Crude OR of STIs for WSW: 0.56 (95% CI 0.39-0.81), for WSWM: 0.99
      (95% CI 0.92-1.06) compared with WSM. Multivariate analysis revealed an
      interaction effect between same-sex sexual behaviour and smoking. Among non
      smokers; WSW adjusted OR was 0.41 (95% CI 0.21-0.80), WSWM adjusted OR was 0.91
      (95% CI 0.81-1.02) compared with WSM. Among smokers; WSW adjusted OR was 1.03
      (95% CI 0.63-1.67) for WSWM adjusted OR was 1.00 (CI 95% 0.93-1.13), compared
      with WSM. CONCLUSION: This study, including the largest cohort of women reporting
      life-time exclusively female partners in an STI study, shows that WSW generally
      are at lower risk for acquiring STIs than WSM. Smoking WSW, however, had the same
      risk for acquiring bacterial STIs as WSM and WSWM. Our study suggests that all
      WSW should receive the same encouragement to test for STIs as WSM.

PMID- 27050293
TI  - Propargyl Vinyl Ethers and Tertiary Skipped Diynes: Two Pluripotent Molecular
      Platforms for Diversity-Oriented Synthesis.
AB  - During the last years, we have been involved in the development of a diversity
      oriented synthetic strategy aimed at transforming simple, linear, and densely
      functionalized molecular platforms into collections of topologically diverse
      scaffolds incorporating biologically relevant structural motifs such as N- and O-
      heterocycles, multifunctionalized aromatic rings, fused macrocycles, etc. The
      strategy merges the concepts of pluripotency (the property of an array of
      chemical functionalities to express different chemical outcomes under different
      chemical environments) and domino chemistry (chemistry based on processes
      involving two or more bond-forming transformations that take place while the
      initial reaction conditions are maintained, with the subsequent reaction
      resulting as a consequence of the functionality installed in the previous one) to
      transform common multifunctional substrates into complex and diverse molecular
      frameworks. This design concept constitutes the ethos of the so-called branching
      cascade strategy, a branch of diversity-oriented synthesis focused on scaffold
      diversity generation. Two pluripotent molecular platforms have been extensively
      studied under this merging (branching) paradigm: C4-O-C3 propargyl vinyl ethers
      (PVEs) and C7 tertiary skipped diynes (TSDs). These are conveniently constructed
      from simple and commercially available raw materials (alkyl propiolates, ketones,
      aldehydes, acid chlorides) through multicomponent manifolds (ABB' three-component
      reaction for PVEs; A2BB' four-component reaction for TSDs) or a simple two-step
      procedure (for PVEs). Their modular origin facilitates their
      structural/functional diversification without increasing the number of synthetic
      steps for their assembly. These two pluripotent molecular platforms accommodate a
      well-defined and dense array of through-bond/through-space interrelated
      functionalities on their structures, which defines their primary reactivity
      principles and establishes the reactivity profile. The PVEs are defined by the
      presence of an alkyne (alkynoate) function and a conjugated enol moiety and their
      mutual through-bond/through-space connectivity. This functional array
      accommodates a number of domino reactions launched either by a Michael addition
      on the alkynoate moiety (conjugated alkynes) or by a [3,3]-propargyl Claisen
      rearrangement (conjugated and nonconjugated alkynes). The reactivity profile of
      the TSDs is defined by the two connected alkynoate moieties (Michael addition)
      and the bispropargylic ester group ([3,3]-sigmatropic rearrangement). Using these
      first reactivity principles, each platform selectively delivers one unique and
      different skeleton (topology) from each domino transformation. Thus, through the
      use of 11 instrumentally simple and scalable domino reactions, we have
      transformed these two linear (rod-symmetric) pluripotent molecular platforms into
      16 different scaffolds incorporating important structural motifs and
      multifunctional decorative patterns. The generated scaffolds entail carbocycles,
      heterocycles, aromatics, beta,gamma-unsaturated esters and acids, and fused
      polycycles. They can be transformed into more elaborated molecular skeletons by
      the use of chemical handles generated in their own domino reactions or by
      appending different functionalities to the pluripotent molecular platform
      (secondary reactivity principles). 

PMID- 27050294
TI  - Anal human papillomavirus infection: prevalence, diagnosis and treatment of
      related lesions.
AB  - Human papillomavirus (HPV) infection is mostly asymptomatic, but may also have
      many diverse clinical signs encompassing benign ano-genital lesions, and
      carcinomas. Recently, interest has also particularly focused on anal cancer
      since, over the last decades, its incidence has been greatly increasing in
      developed countries, both in women and men and is drastically higher in specific
      risk groups, such as men who have sex with men (MSM) and HIV-1 infected
      individuals. Approximately 88% of anal cancer cases worldwide are associated with
      HPV infection. This review summarizes our current understanding of anal HPV
      infection, discussing its epidemiology and risk factors in various populations,
      and the state of the art in the detection of anal HPV infection and its related
      lesions through both cytology and histology. Finally, we discuss the clinical
      management and therapy for these lesions. 

PMID- 27050295
TI  - Life experiences and the acquired capability for suicide in incarcerated men.
AB  - Suicide is a leading cause of death in U.S. prisons. Prisoners may be at risk for
      suicide due to their greater likelihood of experiencing events that promote the
      acquired capability for suicide. The current study examined the associations of
      10 domains of life experiences with the acquired capability for suicide in 399
      male prisoners. All life experience domains were associated with acquired
      capability with certain domains evidencing relatively stronger relations. Results
      support that aggression, thrill seeking, suicidal thoughts and behaviors, and
      accidental injury may be particularly important to the development of the
      acquired capability for suicide in prisoners.

PMID- 27050296
TI  - Nonlinear Plasmonic Sensing.
AB  - We introduce the concept of nonlinear plasmonic sensing, relying on third
      harmonic generation from simple plasmonic nanoantennas. Because of the nonlinear
      conversion process we observe a larger sensitivity to a local change in the
      refractive index as compared to the commonly used linear localized surface
      plasmon resonance sensing. Refractive index changes as small as 10(-3) can be
      detected. In order to determine the spectral position of highest sensitivity, we
      perform linear and third harmonic spectroscopy on plasmonic nanoantenna arrays,
      which are the fundamental building blocks of our sensor. Furthermore,
      simultaneous detection of linear and nonlinear signals allows quantitative
      comparison of both methods, providing further insight into the working principle
      of our sensor. While the signal-to-noise ratio is comparable, nonlinear sensing
      gives about seven times higher relative signal changes.

PMID- 27050297
TI  - Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces
      autophagy in Alzheimer's disease mice.
AB  - Cerebral hypoperfusion and impaired autophagy are two etiological factors that
      have been identified as being associated with the development of Alzheimer's
      disease (AD). Nevertheless, the exact relationships among these pathological
      processes remain unknown. To elucidate the impact of cerebral hypoperfusion in
      AD, we created a unilateral common carotid artery occlusion (UCCAO) model by
      occluding the left common carotid artery in both young and old 3xTg-AD mice. Two
      months after occlusion, we found that ligation increases phospho-Tau (p-Tau) at
      Serine 199/202 in the hippocampus of 3-month-old AD mice, compared to sham
      operated AD mice; whereas, there is no change in the wild type (WT) mice after
      ligation. Moreover, cerebral hypoperfusion led to significant increase of p-Tau
      in both the hippocampus and cortex of 16-month-old AD mice and WT mice. Notably,
      we did not detect any change in Abeta42 level in either young or old AD and WT
      mice after ligation. Interestingly, we observed a downregulation of LC3-II in the
      cortex of aged AD mice and WT mice after ligation. Our results suggest that
      elevated p-Tau and reduced autophagy are major cellular changes that are
      associated with hypoperfusion in AD. Therefore, targeting p-Tau and autophagy
      pathways may ameliorate hypoperfusion-induced brain damage in AD. 

PMID- 27050298
TI  - Escherichia coli DnaE Polymerase Couples Pyrophosphatase Activity to DNA
      Replication.
AB  - DNA Polymerases generate pyrophosphate every time they catalyze a step of DNA
      elongation. This elongation reaction is generally believed as thermodynamically
      favoured by the hydrolysis of pyrophosphate, catalyzed by inorganic
      pyrophosphatases. However, the specific action of inorganic pyrophosphatases
      coupled to DNA replication in vivo was never demonstrated. Here we show that the
      Polymerase-Histidinol-Phosphatase (PHP) domain of Escherichia coli DNA Polymerase
      III alpha subunit features pyrophosphatase activity. We also show that this
      activity is inhibited by fluoride, as commonly observed for inorganic
      pyrophosphatases, and we identified 3 amino acids of the PHP active site.
      Remarkably, E. coli cells expressing variants of these catalytic residues of
      alpha subunit feature aberrant phenotypes, poor viability, and are subject to
      high mutation frequencies. Our findings indicate that DNA Polymerases can couple
      DNA elongation and pyrophosphate hydrolysis, providing a mechanism for the
      control of DNA extension rate, and suggest a promising target for novel
      antibiotics. 

PMID- 27050299
TI  - A squalene synthase-like enzyme initiates production of tetraterpenoid
      hydrocarbons in Botryococcus braunii Race L.
AB  - The green microalga Botryococcus braunii is considered a promising biofuel
      feedstock producer due to its prodigious accumulation of hydrocarbon oils that
      can be converted into fuels. B. braunii Race L produces the C40 tetraterpenoid
      hydrocarbon lycopadiene via an uncharacterized biosynthetic pathway. Structural
      similarities suggest this pathway follows a biosynthetic mechanism analogous to
      that of C30 squalene. Confirming this hypothesis, the current study identifies
      C20 geranylgeranyl diphosphate (GGPP) as a precursor for lycopaoctaene
      biosynthesis, the first committed intermediate in the production of lycopadiene.
      Two squalene synthase (SS)-like complementary DNAs are identified in race L with
      one encoding a true SS and the other encoding an enzyme with lycopaoctaene
      synthase (LOS) activity. Interestingly, LOS uses alternative C15 and C20 prenyl
      diphosphate substrates to produce combinatorial hybrid hydrocarbons, but almost
      exclusively uses GGPP in vivo. This discovery highlights how SS enzyme
      diversification results in the production of specialized tetraterpenoid oils in
      race L of B. braunii. 

PMID- 27050301
TI  - Amino acids as co-amorphous excipients for tackling the poor aqueous solubility
      of valsartan.
AB  - Co-amorphization has recently been shown to be a promising approach for
      stabilizing amorphous drugs and improving the dissolution rate of poorly water
      soluble drugs. In this study, three basic amino acids were chosen as small
      molecular weight excipients to interact with the drug to form co-amorphous
      combinations. The co-amorphous combinations of valsartan (VAL) with l-histidine,
      l-arginine, and l-lysine were prepared by vibrational ball milling. Solid-state
      characterization with X-ray powder diffraction and differential scanning
      calorimetry (DSC) revealed that all of the co-amorphous mixtures were
      homogeneous. The molecular interactions of the co-amorphous mixtures were
      investigated through the glass transition temperature (Tg) in the DSC
      measurements and Fourier transform infrared spectroscopy. The drug remained
      chemically stable during the milling process, and the co-amorphous formulations
      were generally physically stable over at least 3 months at 40  degrees C under
      dry conditions. The dissolution rate of all of the co-amorphous mixtures was
      significantly increased over that of the amorphous VAL alone. The results of this
      study demonstrated the potential of amino acids as small molecular weight
      excipients in co-amorphous formulations to improve the drug solubility and
      dissolution rate.

PMID- 27050302
TI  - Integrative Taxonomy of Southeast Asian Snail-Eating Turtles (Geoemydidae:
      Malayemys) Reveals a New Species and Mitochondrial Introgression.
AB  - Based on an integrative taxonomic approach, we examine the differentiation of
      Southeast Asian snail-eating turtles using information from 1863 bp of
      mitochondrial DNA, 12 microsatellite loci, morphology and a correlative species
      distribution model. Our analyses reveal three genetically distinct groups with
      limited mitochondrial introgression in one group. All three groups exhibit
      distinct nuclear gene pools and distinct morphology. Two of these groups
      correspond to the previously recognized species Malayemys macrocephala (Chao
      Phraya Basin) and M. subtrijuga (Lower Mekong Basin). The third and genetically
      most divergent group from the Khorat Basin represents a previously unrecognized
      species, which is described herein. Although Malayemys are extensively traded and
      used for religious release, only few studied turtles appear to be translocated by
      humans. Historic fluctuations in potential distributions were assessed using
      species distribution models (SDMs). The Last Glacial Maximum (LGM) projection of
      the predictive SDMs suggests two distinct glacial distribution ranges, implying
      that the divergence of M. macrocephala and M. subtrijuga occurred in allopatry
      and was triggered by Pleistocene climate fluctuations. Only the projection
      derived from the global circulation model MIROC reveals a distinct third glacial
      distribution range for the newly discovered Malayemys species. 

PMID- 27050303
TI  - Errors Disrupt Subsequent Early Attentional Processes.
AB  - It has been demonstrated that target detection is impaired following an error in
      an unrelated flanker task. These findings support the idea that the occurrence or
      processing of unexpected error-like events interfere with subsequent information
      processing. In the present study, we investigated the effect of errors on early
      visual ERP components. We therefore combined a flanker task and a visual
      discrimination task. Additionally, the intertrial interval between both tasks was
      manipulated in order to investigate the duration of these negative after-effects.
      The results of the visual discrimination task indicated that the amplitude of the
      N1 component, which is related to endogenous attention, was significantly
      decreased following an error, irrespective of the intertrial interval.
      Additionally, P3 amplitude was attenuated after an erroneous trial, but only in
      the long-interval condition. These results indicate that low-level attentional
      processes are impaired after errors. 

PMID- 27050304
TI  - A Querying Method over RDF-ized Health Level Seven v2.5 Messages Using Life
      Science Knowledge Resources.
AB  - BACKGROUND: Health level seven version 2.5 (HL7 v2.5) is a widespread messaging
      standard for information exchange between clinical information systems. By
      applying Semantic Web technologies for handling HL7 v2.5 messages, it is possible
      to integrate large-scale clinical data with life science knowledge resources.
      OBJECTIVE: Showing feasibility of a querying method over large-scale resource
      description framework (RDF)-ized HL7 v2.5 messages using publicly available drug
      databases. METHODS: We developed a method to convert HL7 v2.5 messages into the
      RDF. We also converted five kinds of drug databases into RDF and provided
      explicit links between the corresponding items among them. With those linked drug
      data, we then developed a method for query expansion to search the clinical data
      using semantic information on drug classes along with four types of temporal
      patterns. For evaluation purpose, medication orders and laboratory test results
      for a 3-year period at the University of Tokyo Hospital were used, and the query
      execution times were measured. RESULTS: Approximately 650 million RDF triples for
      medication orders and 790 million RDF triples for laboratory test results were
      converted. Taking three types of query in use cases for detecting adverse events
      of drugs as an example, we confirmed these queries were represented in SPARQL
      Protocol and RDF Query Language (SPARQL) using our methods and comparison with
      conventional query expressions were performed. The measurement results confirm
      that the query time is feasible and increases logarithmically or linearly with
      the amount of data and without diverging. CONCLUSIONS: The proposed methods
      enabled query expressions that separate knowledge resources and clinical data,
      thereby suggesting the feasibility for improving the usability of clinical data
      by enhancing the knowledge resources. We also demonstrate that when HL7 v2.5
      messages are automatically converted into RDF, searches are still possible
      through SPARQL without modifying the structure. As such, the proposed method
      benefits not only our hospitals, but also numerous hospitals that handle HL7 v2.5
      messages. Our approach highlights a potential of large-scale data federation
      techniques to retrieve clinical information, which could be applied as
      applications of clinical intelligence to improve clinical practices, such as
      adverse drug event monitoring and cohort selection for a clinical study as well
      as discovering new knowledge from clinical information.

PMID- 27050305
TI  - Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote
      Insulin Resistance in Obesity.
AB  - Obesity-induced inflammation mediated by immune cells in adipose tissue appears
      to participate in the pathogenesis of insulin resistance. We show that natural
      killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD)
      increases NK cell numbers and the production of proinflammatory cytokines,
      notably TNFalpha, in epididymal, but not subcutaneous, fat depots. When NK cells
      were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/
      ) mice, obesity-induced insulin resistance improved in parallel with decreases in
      both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue
      inflammation. Conversely, expansion of NK cells following IL-15 administration or
      reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and
      adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These
      results indicate that adipose NK cells control ATMs as an upstream regulator
      potentially by producing proinflammatory mediators, including TNFalpha, and
      thereby contribute to the development of obesity-induced insulin resistance. 

PMID- 27050306
TI  - Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem
      Cells.
AB  - Human pluripotent stem cells (hPSCs) are uniquely dependent on aerobic glycolysis
      to generate ATP. However, the importance of oxidative phosphorylation (OXPHOS)
      has not been elucidated. Detailed amino acid profiling has revealed that
      glutamine is indispensable for the survival of hPSCs. Under glucose- and
      glutamine-depleted conditions, hPSCs quickly died due to the loss of ATP.
      Metabolome analyses showed that hPSCs oxidized pyruvate poorly and that glutamine
      was the main energy source for OXPHOS. hPSCs were unable to utilize pyruvate
      derived citrate due to negligible expression of aconitase 2 (ACO2) and isocitrate
      dehydrogenase 2/3 (IDH2/3) and high expression of ATP-citrate lyase.
      Cardiomyocytes with mature mitochondria were not able to survive without glucose
      and glutamine, although they were able to use lactate to synthesize pyruvate and
      glutamate. This distinguishing feature of hPSC metabolism allows preparation of
      clinical-grade cell sources free of undifferentiated hPSCs, which prevents tumor
      formation during stem cell therapy. 

PMID- 27050307
TI  - Mixture dynamics: Combination therapy in oncology.
AB  - In recent years combination therapies have become increasingly popular in most
      therapeutic areas. We present a qualitative and quantitative approach and
      elucidate some of the challenges and solutions to a more optimal therapy. For
      tumor growth this involves the study of semi-mechanistic cell-growth/kill models
      with multiple sites of action. We introduce such models and analyze their dynamic
      properties using simulations and mathematical analysis. This is done for two
      specific case studies, one involving a single compound and one a combination of
      two compounds. We generalize the notion of Tumor Static Concentration to cases
      when two compounds are involved and develop a graphical method for determining
      the optimal combination of the two compounds, using ideas akin to those used in
      studies employing isobolograms. In studying the dynamics of the second case study
      we focus, not only on the different concentrations, but also on the different
      dosing regimens and pharmacokinetics of the two compounds. 

PMID- 27050308
TI  - The Functional Response of B Cells to Antigenic Stimulation: A Preliminary Report
      of Latent Tuberculosis.
AB  - Mycobacterium tuberculosis (M.tb) remains a successful pathogen, causing
      tuberculosis disease numbers to constantly increase. Although great progress has
      been made in delineating the disease, the host-pathogen interaction is
      incompletely described. B cells have shown to function as both effectors and
      regulators of immunity via non-humoral methods in both innate and adaptive immune
      settings. Here we assessed specific B cell functional interaction following
      stimulation with a broad range of antigens within the LTBI milieu. Our results
      indicate that B cells readily produce pro- and anti-inflammatory cytokines
      (including IL-1beta, IL-10, IL-17, IL-21 and TNF-alpha) in response to
      stimulation. TLR4 and TLR9 based stimulations achieved the greatest secreted
      cytokine-production response and BCG stimulation displayed a clear preference for
      inducing IL-1beta production. We also show that the cytokines produced by B cells
      are implicated strongly in cell-mediated communication and that plasma (memory) B
      cells (CD19+CD27+CD138+) is the subset with the greatest contribution to cytokine
      production. Collectively our data provides insight into B cell responses, where
      they are implicated in and quantifies responses from specific B cell phenotypes.
      These findings warrant further functional B cell research with a focus on
      specific B cell phenotypes under conditions of active TB disease to further our
      knowledge about the contribution of various cell subsets which could have
      implications for future vaccine development or refined B cell orientated
      treatment in the health setting. 

PMID- 27050309
TI  - Brazil's Market for Trading Forest Certificates.
AB  - Brazil faces an enormous challenge to implement its revised Forest Code. Despite
      big losses for the environment, the law introduces new mechanisms to facilitate
      compliance and foster payment for ecosystem services (PES). The most promising of
      these is a market for trading forest certificates (CRAs) that allows landowners
      to offset their restoration obligations by paying for maintaining native
      vegetation elsewhere. We analyzed the economic potential for the emerging CRA
      market in Brazil and its implications for PES programs. Results indicate a
      potential market for trading 4.2 Mha of CRAs with a gross value of US$ 9.2+/-2.4
      billion, with main regional markets forming in the states of Mato Grosso and Sao
      Paulo. This would be the largest market for trading forests in the world.
      Overall, the potential supply of CRAs in Brazilian states exceeds demand,
      creating an opportunity for additional PES programs to use the CRA market. This
      expanded market could provide not only monetary incentives to conserve native
      vegetation, but also environmental co-benefits by fostering PES programs focused
      on biodiversity, water conservation, and climate regulation. Effective
      implementation of the Forest Code will be vital to the success of this market and
      this hurdle brings uncertainty into the market. Long-term commitment, both within
      Brazil and abroad, will be essential to overcome the many challenges ahead. 

PMID- 27050310
TI  - Novel mutations in SKIV2L and TTC37 genes in Malaysian children with
      trichohepatoenteric syndrome.
AB  - Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder that
      is classically associated with intractable diarrhea with an onset within the
      first few months of life. Herein, we investigated and reported novel mutations in
      two causal genes in 3 Malaysian cases. Genomic DNA was extracted from peripheral
      blood obtained from patients in two Malaysian Chinese families. The exons of
      SKIV2L and TTC37 genes were amplified and sequenced by bi-directional sequencing
      to identify the point mutations within the coding sequence. Three Chinese boys
      from two families with characteristic features and clinical course were diagnosed
      with THES. In family-1, two point mutations were identified in the SKIV2L gene
      (c.1891G>A and c.3187C>T). In family-2, a single-nucleotide duplication
      (c.3426dupA) was found in the TTC37 gene. These mutations cause the production of
      abnormal non-functional gene product leading to the clinical manifestations in
      the patients. We reported three point mutations, which have not been previously
      described in other patients with THES in SKIV2L and TTC37 genes, including one
      nonsense, one frameshift, and one missense mutations. 

PMID- 27050311
TI  - Functional results of robotic total intersphincteric resection with hand-sewn
      coloanal anastomosis.
AB  - BACKGROUND: In recent decades there has been an increasing trend toward sphincter
      preserving procedures for the treatment of low rectal cancer. Robotic surgery is
      considered to be particularly beneficial when operating in the deep pelvis, where
      laparoscopy presents technical limitations. The aim of this study was to
      prospectively evaluate the functional outcomes in patients affected by rectal
      cancer after robotic total intersphincteric resection (ISR) with hand-sewn
      coloanal anastomosis. METHODS AND PROCEDURES: From March 2008 to October 2012, 23
      consecutive patients affected by distal rectal adenocarcinoma underwent robotic
      ISR. Operative, clinical, pathological and functional data regarding continence
      or presence of a low anterior resection syndrome (LARS) were prospectively
      collected in a database. RESULTS: Twenty-three consecutive patients were included
      in the study: 8 men and 15 women. The mean age was 60.2 years (range 28-73).
      Eighteen (78.3%) had neoadjuvant radiochemotherapy. Conversion rate was nil. The
      mean operative time was 296.01 min and the mean postoperative hospital stay was
      7.43 +/- 1.73 days. According to Kirwan's incontinence score, good fecal
      continence was shown in 85.7% of patients (Grade 1 and 2) and none required a
      colostomy (Grade 4). Concerning LARS score, the results were as follows: 57.1%
      patients had no LARS; 19% minor LARS and 23.8% major LARS. CONCLUSIONS: Robotic
      total ISR for low rectal cancer is an acceptable alternative to traditional
      procedures. Extensive discussion with the patient about the risk of poor
      functional outcomes or LARS syndrome is mandatory when considering an ISR for
      treatment of low rectal cancer.

PMID- 27050312
TI  - Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and
      Malabsorption in Environmental Enteropathy.
AB  - INTRODUCTION: Environmental enteropathy (EE) is associated with growth failure,
      micronutrient malabsorption and impaired responses to oral vaccines. We set out
      to define cellular mechanisms of impaired barrier function in EE and explore
      protective mechanisms. METHODS: We studied 49 adults with environmental
      enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE);
      histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies;
      and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test.
      RESULTS: CLE images (median 134 for each study) showed virtually ubiquitous small
      intestinal damage. Epithelial defects, imaged by histology and claudin 4
      immunostaining, were predominantly seen at the tips of villi and corresponded
      with leakage imaged in vivo by CLE. In multivariate analysis, circulating log
      transformed LPS was correlated with cell shedding events (beta = 0.83; P = 0.035)
      and with serum glucagon-like peptide-2 (beta = -0.13; P = 0.007). Zinc uptake
      from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in
      multivariate analysis was reduced by HIV, but positively correlated with GLP-2
      (beta = 2.72; P = 0.03). There was a U-shaped relationship between circulating
      LPS and villus surface area. Transcriptomic analysis identified 23 differentially
      expressed genes in severe enteropathy, including protective peptides and
      proteins. CONCLUSIONS: Confocal endomicroscopy, claudin 4 immunostaining and
      histology identify epithelial defects which are probably sites of bacterial
      translocation, in the presence of which increased epithelial surface area
      increases the burden of translocation. GLP 2 and other protective peptides may
      play an important role in mucosal protection in EE.

PMID- 27050313
TI  - Comprehensive identification and profiling of Nile tilapia (Oreochromis
      niloticus) microRNAs response to Streptococcus agalactiae infection through high
      throughput sequencing.
AB  - MicroRNAs are a kind of small non-coding RNAs that participate in various
      biological processes. Deregulated microRNA expression is associated with several
      types of diseases. Tilapia (Oreochromis niloticus) is an important commercial
      fish species in China. To identify miRNAs and investigate immune-related miRNAs
      of O. niloticus, we applied high-throughput sequencing technology to identify and
      analyze miRNAs from tilapia infected with Streptococcus agalactiae at a timescale
      of 72 h divided into six different time points. The results showed that a total
      of 3009 tilapia miRNAs were identified, including in 1121 miRNAs which have
      homologues in the currently available databases and 1878 novel miRNAs. The
      expression levels of 218 tilapia miRNAs were significantly altered at 6 h-72 h
      post-bacterial infection (pi), and these miRNAs were therefore classified as
      differentially expressed tilapia miRNAs. For the 1121 differentially expressed
      tilapia miRNAs target 41961 genes. GO and KEGG enrichment analysis revealed that
      some target genes of tilapia miRNAs were grouped mainly into the categories of
      apoptotic process, signal pathway, and immune response. This is the first report
      of comprehensive identification of O. niloticus miRNAs being differentially
      regulated in spleen in normal conditions relating to S. agalactiae infection.
      This work provides an opportunity for further understanding of the molecular
      mechanisms of miRNA regulation in O. niloticus host-pathogen interactions. 

PMID- 27050314
TI  - Antiviral function of grouper MDA5 against iridovirus and nodavirus.
AB  - Melanoma differentiation-associated gene 5 (MDA5) is a critical member of
      retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family which can
      recognize viral RNA and enhances antiviral response in host cells. In this study,
      a MDA5 homolog from orange spotted grouper (Epinephelus coioides) (EcMDA5) was
      cloned, and its roles on grouper virus infection were characterized. The full
      length EcMDA5 cDNA encoded a polypeptide of 982 amino acids with 74% identity
      with MDA5 homolog from rock bream (Oplegnathus fasciatus). Amino acid alignment
      analysis indicated that EcMDA5 contained three functional domains: two caspase
      activation and recruitment domain (CARDs), a DEAD box helicase-like (DExDc)
      domain, a helicase superfamily C-terminal domain (HELICc), and a C-terminal
      regulatory domain (RD). Upon challenge with Singapore grouper iridovirus (SGIV)
      or polyinosin-polycytidylic acid (poly I:C), the transcript of EcMDA5 was
      significantly up-regulated especially at the early stage post-injection. Under
      fluorescence microscopy, we observed that EcMDA5 mostly localized in the
      cytoplasm of grouper spleen (GS) cells. Interestingly, during virus infection,
      the distribution pattern of EcMDA5 was significantly altered in SGIV infected
      cells, but not in red spotted grouper nervous necrosis virus (RGNNV) infected
      cells, suggested that EcMDA5 might interact with viral proteins during SGIV
      infection. The ectopic expression of EcMDA5 in vitro obviously delayed virus
      infection induced cytopathic effect (CPE) progression and significantly inhibited
      viral gene transcription of RGNNV and SGIV. Moreover, overexpression of EcMDA5
      not only significantly increased interferon (IFN) and IFN-stimulated response
      element (ISRE) promoter activities in a dose dependent manner, but also enhanced
      the expression of IRF3, IRF7 and TRAF6. In addition, the transcription level of
      the proinflammatory factors, including TNF-alpha, IL-6 and IL-8 were differently
      altered by EcMDA5 overexpression during SGIV or RGNNV infection, suggesting that
      the regulation on proinflammatory cytokines by EcMDA5 were also important for
      RGNNV infection. Together, our results demonstrated for the first time that the
      inhibitory effect of fish MDA5 on iridovirus replication might be mainly through
      the regulation of proinflammatory cytokines. 

PMID- 27050315
TI  - The Use of DNA Barcoding on Recently Diverged Species in the Genus Gentiana
      (Gentianaceae) in China.
AB  - DNA barcoding of plants poses particular challenges, especially in
      differentiating, recently diverged taxa. The genus Gentiana (Gentianaceae) is a
      species-rich plant group which rapidly radiated in the Himalaya-Hengduan
      Mountains in China. In this study, we tested the core plant barcode (rbcL + matK)
      and three promising complementary barcodes (trnH-psbA, ITS and ITS2) in 30
      Gentiana species across 6 sections using three methods (the genetic distance
      based method, Best Close Match and tree-based method). rbcL had the highest PCR
      efficiency and sequencing success (100%), while the lowest sequence
      recoverability was from ITS (68.35%). The presence of indels and inversions in
      trnH-psbA in Gentiana led to difficulties in sequence alignment. When using a
      single region for analysis, ITS exhibited the highest discriminatory power (60%
      74.42%). Of the combinations, matK + ITS provided the highest discrimination
      success (71.43%-88.24%) and is recommended as the DNA barcode for the genus
      Gentiana. DNA barcoding proved effective in assigning most species to sections,
      though it performed poorly in some closely related species in sect. Cruciata
      because of hybridization events. Our analysis suggests that the status of G.
      pseudosquarrosa needs to be studied further. The utility of DNA barcoding was
      also verified in authenticating 'Qin-Jiao' Gentiana medicinal plants (G.
      macrophylla, G. crassicaulis, G. straminea, and G. dahurica), which can help
      ensure safe and correct usage of these well-known Chinese traditional medicinal
      herbs. 

PMID- 27050317
TI  - Adolescent risk-taking is predicted by individual differences in cognitive
      control over emotional, but not non-emotional, response conflict.
AB  - While much research on adolescent risk behaviour has focused on the development
      of prefrontal self-regulatory mechanisms, prior studies have elicited mixed
      evidence of a relationship between individual differences in the capacity for
      self-regulation and individual differences in risk taking. To explain these
      inconsistent findings, it has been suggested that the capacity for self
      regulation may be, for most adolescents, adequately mature to produce adaptive
      behaviour in non-affective, "cold" circumstances, but that adolescents have a
      more difficult time exerting control in affective, "hot" contexts. To further
      explore this claim, the present study examined individual differences in self
      control in the face of affective and non-affective response conflict, and
      examined whether differences in the functioning of cognitive control processes
      under these different conditions was related to risk taking. Participants
      completed a cognitive Stroop task, an emotional Stroop task, and a risky driving
      task known as the Stoplight game. Regression analyses showed that performance on
      the emotional Stroop task predicted laboratory risk-taking in the driving task,
      whereas performance on the cognitive Stroop task did not exhibit the same trend.
      This pattern of results is consistent with theories of adolescent risk-taking
      that emphasise the impacts of affective contextual influences on the ability to
      enact effective cognitive control.

PMID- 27050318
TI  - Reconstruction of the tongue and mouth floor with the myofascial vastus lateralis
      free flap after cancer ablation.
AB  - The current study was undertaken to evaluate a novel approach to tongue and mouth
      floor reconstruction using the myofascial vastus lateralis free flap (MVLF). The
      surgical techniques, benefits, complication rate, and the aesthetic and
      functional results are described. A series of six patients underwent functional
      tongue reconstruction between July 2013 and November 2014. The myofascial vastus
      lateralis flap was obtained as follows: the vastus lateralis muscle was exposed,
      the neurovascular pedicle was identified, and the myofascial flap was raised.
      Postoperatively, the neotongue appeared plump and was able to maintain palatal
      contact. Moreover, no obvious decrease in flap volume was observed during the
      follow-up period. Most patients experienced good tongue mobility. Further use of
      the MVLF should confirm whether the mucous membrane on the surface of the flap
      becomes part of the tongue mucosa in the true sense, whether and how well the
      patients will recover their sense of taste, and the degree to which quality of
      life is improved after nerve anastomosis. So far, it appears to be a suitable
      approach to tongue and mouth floor reconstruction. 

PMID- 27050319
TI  - Clarifying Human White Matter.
AB  - Progress in magnetic resonance imaging (MRI) now makes it possible to identify
      the major white matter tracts in the living human brain. These tracts are
      important because they carry many of the signals communicated between different
      brain regions. MRI methods coupled with biophysical modeling can measure the
      tissue properties and structural features of the tracts that impact our ability
      to think, feel, and perceive. This review describes the fundamental ideas of the
      MRI methods used to identify the major white matter tracts in the living human
      brain.

PMID- 27050320
TI  - Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics.
AB  - Ten years of remarkable progress in understanding the fundamental biochemistry of
      Alzheimer's disease have been followed by ten years of remarkable and increasing
      clinical insight into the natural progression of the disorder. The concept of a
      long, intermediary, prodromal phase between the first appearance of amyloid
      plaques and tangles and the manifestation of dementia is now well established.
      The major challenge for the next decade is to chart the many cellular processes
      that underlie this phase and link the biochemical alterations to the clinical
      manifestation of Alzheimer's disease. We discuss here how genetics, new cell
      culture systems, and improved animal models will fuel this work. We anticipate
      that the resulting novel insights will provide a basis for further drug
      development for this terrible disease.

PMID- 27050321
TI  - Ant Genetics: Reproductive Physiology, Worker Morphology, and Behavior.
AB  - Many exciting studies have begun to elucidate the genetics of the morphological
      and physiological diversity of ants, but as yet few studies have investigated the
      genetics of ant behavior directly. Ant genomes are marked by extreme rates of
      gene turnover, especially in gene families related to olfactory communication,
      such as the synthesis of cuticular hydrocarbons and the perception of
      environmental semiochemicals. Transcriptomic and epigenetic differences are
      apparent between reproductive and sterile females, males and females, and workers
      that differ in body size. Quantitative genetic approaches suggest heritability of
      task performance, and population genetic studies indicate a genetic association
      with reproductive status in some species. Gene expression is associated with
      behavior including foraging, response to queens attempting to join a colony,
      circadian patterns of task performance, and age-related changes of task. Ant
      behavioral genetics needs further investigation of the feedback between
      individual-level physiological changes and socially mediated responses to
      environmental conditions.

PMID- 27050323
TI  - Deeper Insights Into Vanishing Bile Duct Syndrome in Lymphoma: A Perplexing
      Entity.

PMID- 27050322
TI  - Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional
      connectivity MRI.
AB  - Domoic acid (DA) is a toxin produced by marine algae and known primarily for its
      role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it
      inflicts on marine mammals, particularly California sea lions. Lethal effects of
      DA are often preceded by seizures and coma. Exposure to DA during development can
      result in subtle and highly persistent effects on brain development and include
      behavioral changes that resemble diagnostic features of schizophrenia and
      anomalies in social behavior we believe are relevant to autism spectrum disorder
      (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice
      exposed in utero to DA for endpoints relevant to ASD, specifically changes in
      social behavior and network structure, the latter measured by resting state
      functional connectivity (rs-fcMRI). We found that male offspring exposed in utero
      to DA expressed reproducible declines in social interaction and atypical patterns
      of functional connectivity in the anterior cingulate, a region of the default
      mode network that is critical for social functioning. We also found disruptions
      in global topology in regions involved in the processing of reward, social, and
      sensory experiences. Finally, we found that DA exposed males expressed a pattern
      of local over-connectivity. These anomalies in brain connectivity bear
      resemblance to connectivity patterns in ASD and help validate DA-exposed mice as
      a model of this mental disability.

PMID- 27050325
TI  - The effect of prehabilitation on the range of motion and functional outcomes in
      patients following the total knee or hip arthroplasty: A pilot randomized trial.
AB  - OBJECTIVE: The study investigated the effect of prehabilitation on the quality of
      life and function in patients having total knee replacement (TKR)/total hip
      replacement (THR). METHODS: A pilot randomized controlled trial with concealed
      allocation, assessor blinding, and intention-to-treat analysis was conducted.
      Sixty-four people undergoing elective lower-limb arthroplasty were included.
      Prehabilitation included one-hour twice-weekly sessions for at least three and a
      maximum of four weeks prior to surgery. Control participants did not complete any
      pre-surgical programs. Health utility and quality of life as measured by the EQ
      5D-3L and the patient-specific functional scale were the primary outcomes
      measured before allocation and eight weeks post-operatively. RESULTS: No between
      group differences were evident in health utility (main effect of the group -0.04
      (95% Confidence Interval [CI] -0.16 to 0.08, p = 0.50) or patient-specific
      functional scale (main effect of the group -0.59 (95% CI -1.8 to 0.6, p = 0.73),
      but the group-by-joint interaction effects for the timed up and go (TUG) (7.6
      (95% CI -0.9 to 16.1, p = 0.08)) and the EQ-5D VAS (-18.3 (95% CI -41.1 to 4.5),
      p = 0.11) were larger. Prehabilitation participants' knee flexion improved by
      12.6 degrees (95% CI 5.2-20, p = 0.001). CONCLUSIONS: Prehabilitation improved
      knee flexion, but this did not translate into improved functional mobility or
      quality of life.

PMID- 27050326
TI  - Support workers as agents for health behavior change: An Australian study of the
      perceptions of clients with complex needs, support workers, and care
      coordinators.
AB  - An expanding aging population has placed increased demands on health care
      resources in many countries. Enhancing community aged care support workers' role
      to support greater client self-management and reablement is therefore timely.
      This article presents perceptions of the impact of an Australian practice change
      initiative designed to enhance knowledge, skills, and confidence of support
      workers to support behavior change in clients with complex health care needs. A
      comprehensive training program was delivered in 2013. Methods included thematic
      analysis of interviews with clients, focus groups with support workers and
      coordinators, and collection of case studies of client/support worker behavior
      change interactions. Client, support worker, and coordinator responses were
      highly positive, reporting improvement in the quality of interactions with
      clients, client health outcomes, care coordination, communication, and teamwork.
      Mental health literacy remained the biggest knowledge gap. This research showed
      that support workers are ideally placed to be more actively involved in
      motivating clients to achieve behavior change goals.

PMID- 27050327
TI  - Serum of patients with active rheumatoid arthritis inhibits differentiation of
      osteochondrogenic precursor cells.
AB  - Delayed fracture healing is frequently experienced in patients with systemic
      inflammation such as during rheumatoid arthritis (RA). The reasons for this are
      diverse, but could also be caused by inflammatory cytokines and/or growth factors
      in serum from patients with active disease. We hypothesized that serum from
      patients with active RA contains circulating inflammatory factors that inhibit
      differentiation of osteochondrogenic precursors. Serum was obtained from 15
      patients with active RA (active RA-sera) and from the same patients in clinical
      remission 1 year later (remission RA-sera; controls). The effect of active RA
      sera on osteochondrogenic differentiation of chondrogenic ATDC5 cells and primary
      human periosteum-derived progenitor cells (HPDC) was determined in micromass
      culture. In ATDC5 cells, active RA-sera reduced Ki67 transcription levels by 40%
      and cartilage matrix accumulation by 14% at day 14, and Alp transcription levels
      by 16%, and matrix mineralization by 17% at day 21 compared with remission RA
      sera. In HPDCs, active RA-sera inhibited metabolic activity by 8%, SOX9
      transcription levels by 14%, and cartilage matrix accumulation by 7% at day 7
      compared with remission RA-sera. In conclusion, sera from patients with active RA
      negatively affect differentiation of osteochondrogenic precursors, and as a
      consequence may contribute to delayed fracture healing in these patients.

PMID- 27050328
TI  - Safety of Varenicline for Smoking Cessation in Psychiatric and Addicts Patients.
AB  - The safety of varenicline in the treatment of tobacco dependence has been
      questioned, in psychiatric patients. However, most published studies have not
      included psychiatric patients. OBJECTIVE: Assess the safety of varenicline for
      smoking cessation in patients with psychiatric disorders. METHODS: This is a
      prospective, longitudinal, multicenter study. The sample is composed of three
      groups (patients with psychotic disorder, patients with alcohol dependence
      disorder and patients addicts in methadone maintenance treatment). Patients were
      recruited consecutively between September 2008 and June 2009 from 11 centers. All
      patients received a standardized smoking cessation program with varenicline and
      psychological support. Adverse events of the drug were monitored at weeks 1, 2,
      4, 6, 8, and 12 of treatment. Bivariate analysis has been used. RESULTS: None of
      the 90 patients included, presented a serious adverse event. The most frequent
      adverse effect was dry mouth (28.9%), followed by the presence of flatulence
      (27.8%), abnormal dreams (27.8%), and nausea (22%), especially between weeks 2
      and 6 of treatment. None of the patients referred intense suicidal ideation,
      although two referred to moderate suicidal ideation, which was solved in one case
      and in the other, treatment was discontinued. Four participants (4.4%) abandoned
      treatment because of gastrointestinal symptoms. The initial dose of varenicline
      was reduced in 25% of patients during the study. CONCLUSIONS: Gastrointestinal
      adverse events are the most incident in this sample of psychiatric patients and
      no exacerbation of psychiatric symptoms was detected, thus indicating a good
      safety record for varenicline use for smoking cessation in psychiatric patients.

PMID- 27050329
TI  - Probing the binding interaction of AKR with human serum albumin by multiple
      fluorescence spectroscopy and molecular modeling.
AB  - Human serum albumin (HSA) is the major transport protein affording endogenous and
      exogenous substances in plasma. It can affect the behavior and efficacy of
      chemicals in vivo through the binding interaction. AKR (3-O-alpha-l
      arabinofuranosyl-kaempferol-7-O-alpha-l-rhamnopyranoside) is a flavonoid
      diglycoside with modulation of estrogen receptors (ERs). Herein, we investigated
      the binding interaction between AKR and HSA by multiple fluorescence spectroscopy
      and molecular modeling. As a result, AKR specifically binds in site I of HSA
      through hydrogen bonds, van der Waals force, and electrostatic interaction. The
      formation of AKR-HSA complex in binding process is spontaneously exothermic and
      leads to the static fluorescence quenching through affecting the microenvironment
      around the fluorophores. The complex also affects the backbone of HSA and makes
      AKR access to fluorophores. Molecular modeling gives the visualization of the
      interaction between AKR and HSA as well as ERs. The affinity of AKR with HSA is
      higher than the competitive site marker Warfarin. In addition, docking studies
      reveal the binding interaction of AKR with ERs through hydrogen bonds, van der
      Waals force, hydrophobic, and electrostatic interactions. And AKR is more
      favorable to ERbeta. These results unravel the binding interaction of AKR with
      HSA and mechanism as an ERs modulator.

PMID- 27050330
TI  - Structures similar to lipid emulsions and liposomes.
      Dipalmitoylphosphatidylcholine, cholesterol, Tween 20-Span 20 or Tween 80-Span 80
      in aqueous media.
AB  - In the present work, we show that we obtained nanometric structures made of
      water, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol
      (Chol), and a mixture of ethoxylated and non-ethoxylated sorbitan fatty acid
      esters (Tween 20, Span 20, Tween 80, and Span 80) by mixing all of them near the
      cloud point temperature (cp) of the ethoxylated surfactant. The influence that
      the constituents had on the size of the particle was determined by a pseudo
      ternary phase diagram of water/Tween-Span/DPPC-Chol; the colloidal particles
      obtained were studied by differential scanning calorimetry, confocal fluorescence
      microscopy, scanning electron microscopy, and atomic force microscopy. These
      studies were made for all the systems with at least 23 d of colloidal stability.
      The most stable system was obtained with the Tween 80-Span 80 pair, behaving as a
      typical suspension for 48 d; this system was made of water, Tween 80-Span 80
      (80:20), DPPC-Chol (95:5) in a corresponding molar ratio of 48:37:100:10. The
      colloidal particles obtained were a kind of emulsion and liposome structures. The
      second stable system was obtained with the same mixture, but in a molar ratio of
      8:6:9:0, its structure was also a kind of emulsion particles. In both systems and
      in other less stable ones, the "emulsion particle" was completely new, it
      structurally corresponds to a nucleus of mixed micelles surrounded by at least
      one bilayer of DPPC.

PMID- 27050331
TI  - Lung Ablation: Whats New?
AB  - Lung cancer had an estimated incidence of 221,200 in 2015, making up 13% of all
      cancer diagnoses. Tumor ablation is an important treatment option for nonsurgical
      lung cancer and pulmonary metastatic patients. Radiofrequency ablation has been
      used for over a decade with newer modalities, microwave ablation, cryoablation,
      and irreversible electroporation presenting as additional and possibly improved
      treatment options for patients. This minimally invasive therapy is best for small
      primary lesions or favorably located metastatic tumors. These technologies can
      offer palliation and sometimes cure of thoracic malignancies. This article
      discusses the current available technologies and techniques available for tumor
      ablation. 

PMID- 27050332
TI  - A comparison of the clinical usefulness of neck circumference and waist
      circumference in individuals with severe obesity.
AB  - : Purpose/Aim: Neck circumference (NC) is an emerging anthropometric parameter
      that has been proposed to reflect metabolic health. The aim of the current study
      was to compare its clinical usefulness to waist circumference (WC) in the
      assessment of individuals with severe obesity. MATERIALS AND METHODS: A total of
      255 subjects participated in the study. All anthropometric measurements were done
      by a single medical professional. Biochemical measurements included oral glucose
      tolerance tests (OGTTs), fasting insulin, lipids, and hepatic enzymes. RESULTS:
      The mean age of the participants was 49 +/- 12 years with the mean body mass
      index (BMI) of 36.9 +/- 6.2 kg/m2. Correlation analyses revealed that while WC
      was better associated with adiposity parameters, it was of little use in
      comparison to NC with regard to metabolic outcomes. In men, NC was positively
      associated with fasting plasma glucose, fasting insulin, FINDRISC scores. ROC
      analyses showed NC was better in distinguishing type 2 diabetes (AUC = 0.758; p <
      0.001), insulin resistance (AUC = 0.757; p = 0.001), metabolic syndrome (AUC =
      0.724; p < 0.001), and hypertension (AUC = 0.763; p = 0.001). Similar
      correlations were observed in women. Using binary logistic regression, we
      determined that a NC of >=35 cm in women and >=38 cm in men are valuable cut-off
      values to use in the everyday practice. CONCLUSION: In individuals with severe
      obesity, NC performs better than WC in the assessment of metabolic health.

PMID- 27050333
TI  - Influence of Social Deprivation on Outcome of Open Arterial Surgery in Tertiary
      Care: An Observational Study.
AB  - BACKGROUND AND OBJECTIVE: Health equity is playing an increasing role in British
      government health policy. Evidence of social deprivation affecting outcomes in
      surgery is poor. This study aimed to assess the influence of social deprivation
      on the outcome of major arterial surgery. MATERIALS AND METHODS: A retrospective
      cohort study was undertaken in patients undergoing elective or emergency open
      surgery for abdominal aortic aneurysms or lower limb arterial reconstruction over
      an eight and a half year period within one institution. Patient deprivation was
      calculated for each patient with the Index of Multiple Deprivation (IMD) score.
      This was then entered into multivariate models to determine its effect on
      mortality and postoperative length of stay after adjustment for confounders.
      RESULTS: Five hundred and six patients were included in the study. There were 45
      deaths (8.9%) and median (IQR) postoperative length of stay was 8 (4-15) days.
      The median (IQR) IMD score was 46.4 (28.3-64.5). IMD score correlated with ASA
      grade and was significantly higher in smokers, patients with respiratory disease
      and those with left ventricular failure. IMD (OR = 1.01; 95% CI = 0.99-1.03; p =
      .45) did not affected mortality, which was associated with aortic surgery,
      emergency surgery, and high ASA grade. Postoperative length of stay, which was
      longer with/after aortic surgery, tissue loss, emergency surgery, high ASA grade,
      low haemoglobin, and age over 80 years was also independent of deprivation
      (Spearman's rho = -0.49, p = .28). DISCUSSION: No effect of social deprivation on
      mortality or length of stay in patients undergoing major arterial surgery was
      identified.

PMID- 27050334
TI  - Free Vascularized Fibular Graft is Reliable in Upper Extremity Long-Bone
      Reconstruction with Good Long-Term Outcomes.
AB  - Background Free vascularized fibular graft is useful in upper extremity long-bone
      reconstruction. The authors studied the reliability and long-term outcomes of
      this technique. Methods The authors included 20 patients with a minimum follow-up
      of 24 months in this study, and retrospectively reviewed patients' hospital
      records and used a preinformation form, the Disabilities of the Arm, Shoulder and
      Hand (DASH), the Lower Extremity Functional Scale (LEFS), and the 15D health
      related quality of life (HRQoL) instrument to perform a cross-sectional
      assessment. Results A total of 9 adults and 11 children underwent vascularized
      fibular transfer for radical tumor resection (n = 13), infection (n = 1), injury
      (n = 3), or secondary pseudoarthrosis (n = 3) in various locations of the upper
      extremity. The median follow-up period was 6 years. Six reoperations proved
      necessary: one early reanastomosis and five revisions with cancellous bone
      grafting to enhance union. Altogether, 19 of the 20 grafts survived: one graft
      failed due to infection. One arm was amputated due to tumor recurrence. The
      median duration of bone union was 12 months. One graft never achieved distal
      union, whereas another developed nonunion after a stress fracture. Ten patients
      completed the questionnaires, with a median of 15.3 years postoperatively. The
      results revealed functional capabilities ranging from no restrictions to
      significantly impaired, and an HRQoL comparable to that of an age-standardized
      general population. Conclusion The free vascularized fibular graft is viable in
      different age groups to reconstruct upper extremity long-bone defects in cases of
      radical bone resection, extensive injury, and diaphyseal pseudoarthrosis. The
      long-term outcomes support the use of this technique. 

PMID- 27050335
TI  - Incidence and Type of Errors in Microsurgical Technique in Surgical Trainees.
AB  - Background The purpose of our study was first to identify microsurgical errors
      and their incidence. Identifying these common errors and the theoretical approach
      to prevent or repair them may provide benefit to trainees in the laboratory
      setting and, ultimately, in the clinical setting. Methods Using a rat femoral
      artery anastomoses model for resident microsurgical training, direct staff
      observation with real-time feedback and error identification was employed. Types
      of microsurgical errors were recorded and instructor feedback relayed to five
      resident participants. Results Errors were cataloged into five main categories:
      insufficient approximation (26.1%), vessel backwall (21.7%), incomplete bites
      (19.6%), tissue tear (19.6%), and irregular widths (13.0%). Further subdivision
      of the incomplete bite error based on vessel layer violated was performed.
      Representative figures were created outlining these errors. Conclusions We
      present common microsurgical errors in trainees and a training model with
      synchronous feedback. Visual images were designed outlining these errors as an
      adjunct for teaching. 

PMID- 27050336
TI  - A Novel Method to Estimate the Weight of the DIEP Flap in Breast Reconstruction:
      DIEP-W, a Simple Calculation Formula Using Paraumbilical Flap Thickness.
AB  - Background Preoperative estimation of abdominal flap volume is valuable for
      breast reconstruction, especially in lean patients. The purpose of this study was
      to develop a formula to estimate the weight of the deep inferior epigastric
      artery perforator (DIEP) flap using unidimensional parameters. Methods We
      retrospectively collected data on 100 consecutive patients who underwent breast
      reconstruction using the DIEP flap. Multiple linear regression analysis was used
      to develop a formula to estimate the weight of the flap. Predictor variables
      included body mass index, height of the flap, width of the flap, and flap
      thickness on computed tomography angiographic images at three paraumbilical
      sites: 5 cm right, left, and inferior from the umbilicus. Then we prospectively
      tested the accuracy of the developed formula in 38 consecutive patients who
      underwent breast reconstruction with free DIEP flaps. Results A calculation
      formula and a smartphone application, DIEP-W was developed from retrospective
      analysis (R (2) = 92.7%, p < 0.001). In the prospective study, the average
      estimated weight was 96.3% of the actual weight, giving the formula a mean
      absolute percentage error of 7.7% (average differences of 45 g). The flap size in
      the prospective group was significantly smaller (p < 0.001) and donor-site
      complications were less (p = 0.002) than those of retrospective group. Conclusion
      Surgeons can easily calculate the DIEP weight with varying flap dimensions in a
      real-time fashion using this formula during preoperative planning and
      intraoperative design. Estimating the flap weight facilitates economical use of
      the flap, which can lead to reduced donor-site complications. 

PMID- 27050337
TI  - Perioperative Acute Kidney Injury: Prevention Rather Than Cure.

PMID- 27050338
TI  - Three-Dimensional High-Throughput Cell Encapsulation Platform to Study Changes in
      Cell-Matrix Interactions.
AB  - In their native extracellular microenvironment, cells respond to a complex array
      of biochemical and mechanical cues that can vary in both time and space. High
      throughput methods that allow characterization of cell-laden matrices are
      valuable tools to screen through many combinations of variables, ultimately
      helping to evolve and test hypotheses related to cell-ECM signaling. Here, we
      developed a platform for high-throughput encapsulation of cells in peptide
      functionalized poly(ethylene glycol) hydrogels. Hydrogels were synthesized using
      a thiol-ene, photoclick reaction, which allowed the cell matrix environment to be
      modified in real time. Matrix signals were dynamically altered by in situ
      tethering of RGDS (0-1.5 mM), a fibronectin-derived adhesive peptide that induced
      more elongation than RLD or IKVAV, and/or by increasing the matrix modulus (1 to
      6 kPa). This method was demonstrated with aortic valvular interstitial cells
      (VICs), a population of cells responsible for the pathological fibrosis and
      matrix remodeling that leads to aortic stenosis. VIC response to cell-matrix
      interactions was characterized by quantifying cell morphology and the fraction of
      cells exhibiting alpha-smooth muscle actin (alphaSMA) stress fibers, a hallmark
      of the myofibroblast phenotype. VICs elongated in response to RGDS addition, with
      a dramatic change in morphology within 24 h. Myofibroblast activation was also
      dependent on RGDS addition, with VICs exhibiting high activation (16-24%) in 1
      kPa gels with RGDS. Response to RGDS was path-dependent, with the amount of time
      exposed to the adhesive ligand important in determining VIC morphology and
      activation. Although VIC aspect ratios were dependent on the amount of time spent
      in a stiff vs soft gel, low levels of VIC activation (<=4%) were observed in any
      gels cultured in higher modulus (6 kPa vs 1 kPa) microenvironments.

PMID- 27050339
TI  - Epidemiologic patterns of disease expression in sarcoidosis: age, gender and
      ethnicity-related differences.
AB  - OBJECTIVES: To evaluate the influence of age, gender and ethnicity in the
      clinical presentation of sarcoidosis in a cohort of Spanish patients. METHODS: We
      analysed 175 consecutive patients diagnosed with sarcoidosis between 1990 and
      2014 in the Hospital Clinic of Barcelona, Spain. Sarcoidosis was diagnosed
      according to the 1999 WASOG criteria. Organ involvement was defined using the
      2014 WASOG organ assessment instrument. RESULTS: There were 110 women and 65 men,
      with a mean age at diagnosis of 47.31 +/- 15.46 years (range, 16-92); 23% of
      patients were born outside Spain. Women had a higher mean age (p=0.027), a higher
      frequency of cutaneous (OR=2.28) and musculoskeletal (OR=2.73) symptoms at
      diagnosis, and a lower frequency of cumulated WASOG involvements including renal
      involvement (OR=0.17), hypercalcaemia (OR=0.20) and raised ACE levels (OR=0.30).
      Patients aged >=65 years had a lower frequency of cutaneous (OR=0.23) and
      musculoskeletal (OR=0.13) symptomatology at diagnosis and a higher frequency of
      cumulated WASOG involvements including renal involvement (OR=18.70) and
      calcium/vitamin D abnormalities (OR=5.31). According to ethnicity, non-Spanish
      born patients had a lower mean age (40 vs. 49 years, p=0.001), a higher
      predominance of females (68% vs. 54%, p=0.036) and a higher frequency of
      radiographic stages I/II at diagnosis (97% vs. 78%, p=0.041) in comparison with
      Spanish-born patients. CONCLUSIONS: Using the new 2014 WASOG organ assessment
      instrument, we found that epidemiological features (age at diagnosis, gender and
      ethnicity) play a significant role in the presentation of sarcoidosis. Variations
      in these epidemiological features may aid early diagnostic suspicion, the search
      for histopathological confirmation and the prompt introduction of the appropriate
      therapy.

PMID- 27050340
TI  - Pilot aerobic membrane bioreactor and nanofiltration for municipal landfill
      leachate treatment.
AB  - The purpose of this article is to evaluate the integration of the air stripping,
      membrane bioreactor (MBR) and nanofiltration (NF) processes for the treatment of
      landfill leachate (LFL). Pretreatment by air stripping, without adjustment of pH,
      removed 65% of N-NH3 present in LFL. After pretreatment, the effluent was treated
      in MBR obtaining 44% of COD removal, and part of the N-NH3 was converted to
      nitrite and nitrate, which was later removed in the post-treatment.
      Nanofiltration was shown to be an effective process to improve the removal of
      organic compounds, the high toxicity present in LFL and nitrite and nitrate
      generated in the MBR. The system (air stripping + MBR + nanofiltration) obtained
      great efficiency of removal in most parameters analyzed, with overall removal of
      COD, ammonia, color and toxicity approximately 88, 95, 100 and 100%,
      respectively. By this route, treated landfill leachate may be reused at the
      landfill as water for dust arrestment and also as earth work on construction
      sites. 

PMID- 27050341
TI  - A disposable, roll-to-roll hot-embossed inertial microfluidic device for size
      based sorting of microbeads and cells.
AB  - Inertial microfluidics has been a highly active area of research in recent years
      for high-throughput focusing and sorting of synthetic and biological
      microparticles. However, existing inertial microfluidic devices always rely on
      microchannels with high-aspect-ratio geometries (channel width w < channel height
      h) and small cross-sections (w*h < 50 * 100 MUm(2)). Such deep and small
      structures increase fabrication difficulty and can limit manufacturing by large
      scale and high-throughput production approaches such as roll-to-roll (R2R) hot
      embossing. In this work, we present a novel inertial microfluidic device using
      only a simple and low-aspect-ratio (LAR) straight microchannel (w > h) to achieve
      size-based sorting of microparticles and cells. The simple LAR geometry of the
      device enables successful high-throughput fabrication using R2R hot embossing.
      With optimized flow conditions and channel dimensions, we demonstrate continuous
      sorting of a mixture of 15 MUm and 10 MUm diameter microbeads with >97% sorting
      efficiency using the low-cost and disposable R2R chip. We further demonstrate
      size-based sorting of bovine white blood cells, demonstrating the ability to
      process real cellular samples in our R2R chip. We envision that this R2R hot
      embossed inertial microfluidic chip will serve as a powerful yet low-cost and
      disposable tool for size-based sorting of synthetic microparticles in industrial
      applications or cellular samples in cell biology research and clinical
      diagnostics.

PMID- 27050342
TI  - "FakeBooks"--predatory journals: The dark side of publishing.

PMID- 27050343
TI  - Detection of the early keratoconus based on corneal biomechanical properties in
      the refractive surgery candidates.
AB  - CONTEXT: Subclinical keratoconus is contraindication to refractive surgery. The
      currently used methods of preoperative screening do not always allow
      differentiating between healthy eyes and those with subclinical keratoconus. AIM:
      To evaluate biomechanical parameters of the cornea, waveform score (WS), and
      intraocular pressure (IOP) as potentially useful adjuncts to the diagnostic
      algorithm for precise detection of the early keratoconus stages and selection of
      refractive surgery candidates. SETTINGS AND DESIGN: Department of Ophthalmology
      and prospective cross-sectional study. PATIENTS AND METHODS: Patients enrolled in
      the study were diagnosed with refractive disorders. We assessed parameters of
      corneal biomechanics such as corneal hysteresis (CH), corneal resistance factor
      (CRF), Goldman-correlated IOP (IOPg), corneal compensated IOP, WS, and
      keratoconus match index (KMI). They were classified into one of three groups
      based on the predefined KMI range: Group 1 (from 0.352 to 0.757) - 45 eyes, Group
      2 (from -0.08 to 0.313) - 52 eyes, and Group 0 - control group (from 0.761 to
      1.642) - 80 eyes. RESULTS: In both study groups, IOPg, CRF, and CH were decreased
      when compared to control (P < 0.0001). In control group, there was positive
      correlation between CH and KMI (P < 0.05), with no correlations in any of the two
      study groups. CRF correlated positively with KMI in control (P < 0.0001) and in
      Group 2 (P < 0.05). CONCLUSIONS: CH and CRF, together with WS and IOPg, consist a
      clinically useful adjunct to detect subclinical keratoconus in patients referred
      for refractive surgery when based on KMI staging.

PMID- 27050344
TI  - Spectral analysis of intraocular pressure pulse wave in ocular hypertensive and
      primary open angle glaucoma patients.
AB  - CONTEXT: In attempt to find an alternative way to determine conversion from
      ocular hypertension to primary open angle glaucoma (POAG) (besides visual field
      and optic disc changes), we analyzed intraocular pressure (IOP) pulse wave in
      spectral domain. AIMS: The aim of this study was to test the potential
      differences in spectral content of IOP pulse wave between ocular hypertension and
      POAG patients, which could indicate conversion. SETTINGS AND DESIGN: Cross
      sectional study designed to test the differences in the spectral content of
      pressure pulse wave between nontreated ocular hypertensive and nontreated,
      freshly diagnosed POAG patients. METHODS: The total of 40 eyes of 40 subjects was
      included: 20 previously untreated ocular hypertensive patients, and 20 previously
      untreated POAG patients. Continuous IOP measuring gained by dynamic contour
      tonometry was submitted to fast Fourier transform signal analysis and further
      statistical data processing. Statistics Analysis Used: Ocular and systemic
      characteristics of the tested subjects were compared by analysis of variance
      appropriate for this study design. A P < 0.05 was considered to be statistically
      significant. RESULTS: Higher spectral components of the IOP pulse wave was
      discerned up to the fifth harmonic in both of the tested groups. No statistically
      significant differences were found in any of the tested harmonic amplitudes.
      CONCLUSIONS: There are no differences in the spectral content of IOP pulse wave
      between ocular hypertensive and primary open angle glaucoma patients which could
      be indicative for conversion.

PMID- 27050345
TI  - A retrospective survey of childhood glaucoma prevalence according to Childhood
      Glaucoma Research Network classification.
AB  - PURPOSE: To evaluate the Childhood Glaucoma Research Network (CGRN)
      classification system and describe the prevalence of each subtype according to
      this classification. MATERIALS AND METHODS: Retrospectively, the medical records
      of 205 consecutive childhood glaucoma and glaucoma suspect patients at an urban
      tertiary care center were reviewed. The initial diagnosis and new diagnosis
      according to CGRN classification were recorded. RESULTS: All patients fit one of
      the seven categories of the new classification. Seventy-one percent of diagnoses
      were changed upon reclassification. Twenty-three percent of patients had primary
      glaucoma (juvenile open-angle glaucoma and primary congenital glaucoma [PCG]);
      36% had secondary glaucoma (glaucoma associated with nonacquired ocular
      anomalies; glaucoma associated with nonacquired systemic disease or syndrome;
      glaucoma associated with acquired condition; and glaucoma following cataract
      surgery); and 39% were glaucoma suspect. Of the patients diagnosed with glaucoma,
      PCG was the most common diagnosis, seen in 32% of patients. CONCLUSION: The CGRN
      classification provides a useful method of classifying childhood glaucoma.

PMID- 27050346
TI  - Ab-interno scleral suture loop fixation with cow-hitch knot in posterior chamber
      intraocular lens decentration.
AB  - AIM OF STUDY: To describe a simplified ab-interno cow-hitch suture fixation
      technique for repositioning decentered posterior chamber intraocular lens (PC
      IOL). MATERIALS AND METHODS: Two cases are presented with the surgical correction
      of decentered and subluxated IOL. Ab-interno scleral suture fixation technique
      with hitch-cow knot in the eye was performed with a ciliary sulcus guide
      instrument and 1 year follow-up was completed. RESULTS: Both of the patients had
      well centered lenses postoperatively. Corrected distant and near visual acuities
      of the patients were improved. There was no significant postoperative
      complication. In the follow-up period of 1 year, no evidence of suture erosion
      was found. CONCLUSIONS: Ab-interno scleral suture loop fixation with hitch-cow
      knot in the eye was effective in repositioning decentered or subluxated PC IOLs
      with excellent postoperative centered lenses and visual outcomes.

PMID- 27050347
TI  - Brinzolamide/timolol versus dorzolamide/timolol fixed combinations: A hospital
      based, prospective, randomized study.
AB  - PURPOSE: To compare the efficacy and tolerability of brinzolamide/timolol (BT)
      and dorzolamide/timolol (DT) fixed combinations on intraocular pressure (IOP)
      reduction. METHODS: Patients with primary open angle glaucoma or normal tension
      glaucoma were randomized to receive either BT or DT. IOPs were measured at
      baseline, 2 weeks, and 1, 2, and 3 months. The primary outcome measures were the
      mean change in IOP from baseline at each visit. Secondary outcome measures
      included the tolerability of each fixed combination. RESULTS: Seventy-three
      patients (73 eyes) were included; 37 eyes in BT group and 36 eyes in DT group.
      Baseline mean IOP were 24.14 +/- 4.5 and 29.53 +/- 6 mmHg for BT and DT,
      respectively (P < 0.001). Both BT and DT provided statistically significant mean
      IOP reductions from baseline values within each group at all study visits (P <
      0.001). DT provided greater mean IOP reductions from baseline than BT at each
      visit which was statistically significant at 2 weeks (P = 0.037). Mean percentage
      of IOP reduction was 24.35% and 46.33% at 2 weeks (P < 0.001), and 24.65% and 47%
      at 3 months (P < 0.001) for BT and DT, respectively. Patients' tolerability
      appeared to be better for DT than for BT with complete ocular comfort without any
      ocular adverse effects in 31 patients (81.1%) in DT group and 11 patients (29.7%)
      in BT group (P < 0.001). CONCLUSION: Both drops provide effective IOP reduction
      which was greater, and patients were more likely to achieve lower target
      pressures with DT than with BT.

PMID- 27050348
TI  - Can higher end tonometers be used interchangeably in routine clinical practice?
AB  - CONTEXT: Precise intraocular pressure (IOP) measurement is important in glaucoma
      practise. Various instruments are available today to accurately measure IOP.
      Thus, the question arises about which instrument to use and whether all of them
      can be used interchangeably. AIMS: To assess the agreement between noncontact
      tonometer (NCT), rebound tonometer (RBT), Goldmann applanation tonometer (GAT),
      and dynamic contour tonometer (DCT) in measuring IOP. SUBJECTS AND METHODS: 499
      eyes of 250 patients were evaluated during a period of 24 months from September
      2010 to August 2012 and measurement of IOP by NCT, RBT, GAT, and DCT was done in
      the given sequence. The agreement was assessed by use of the Bland-Altman plot
      keeping GAT as a gold standard technique. RESULTS: The mean IOP value of NCT,
      RBT, GAT, and DCT was 15.9 +/- 5.5, 15.9 +/- 5.8, 15.9 +/- 4.9, and 16.0 +/- 4.7
      mm of Hg, respectively. The limits of agreement of GAT with DCT, NCT, and RBT
      were found to be +5.4 to -5.2, -4.7 to +4.6, and -5.2 to +5.1 mm of Hg,
      respectively. CONCLUSIONS: A positive and strong correlation was found between
      newer tonometers and GAT, but the limit of agreement was clinically unacceptable.
      The use of a single tonometer should be practised at a glaucoma clinic for a
      patient at each follow-up.

PMID- 27050349
TI  - Anterior and posterior segment parameters measured with Fourier domain optical
      coherence tomography in photopic and scotopic conditions.
AB  - PURPOSE: To compare anterior and posterior segment parameters measured with the
      iVue-100 optical coherence tomography (OCT) in photopic and scotopic conditions.
      METHODS: Central and peripheral corneal thickness, retinal nerve fiber layer and
      macula thickness were measured using the iVue-100 OCT in 47 healthy individuals
      at a higher education institution in photopic (958 lux) and scotopic (0.03 lux)
      conditions. RESULTS: As the lighting conditions changed from scotopic to
      photopic, a significant change in pupil size was noted (P < 0.001). However,
      there was no significant difference in central corneal thickness measurements
      with this change in surrounding illumination with only the temporal peripheral
      corneal area showing a significant difference (3.44 MUm thinner). No significant
      differences were found in the retinal nerve fiber layer thickness. A significant
      decrease in the reading was noted in only the inferior (P = 0.05) and temporal (P
      = 0.05) inner macula area. CONCLUSION: Change in the ambient lighting conditions
      does not result in a clinically significant difference in corneal, retinal nerve
      fiber layer, and macula thickness when measured with the iVue-100 OCT.

PMID- 27050350
TI  - Phototherapeutic keratectomy for recurrent granular dystrophy in postpenetrating
      keratoplasty eyes.
AB  - PURPOSE: The purpose is to assess the clinical and visual outcome after
      phototherapeutic keratectomy (PTK) procedure in eyes with prior penetrating
      keratoplasty (PKP) for granular corneal dystrophy (GCD) and the time of
      performance of repeat PTK for recurrence. METHODS: PTK was performed for visually
      significant recurrence: A reduction in best-corrected visual acuity (BCVA) by >2
      lines over BCVA before recurrence was considered as visually significant
      recurrence. Three eyes had amniotic membrane patch performed with PTK. The main
      outcome measures were a recurrence of GCD, clinical course, and visual outcome.
      Intervals between repeat PTK procedures were noted. RESULTS: Six patients (n = 10
      eyes; males: 4, mean age 39 +/- 13.97 years) underwent PTK. The mean pachymetry
      before first PTK was 527.1 +/- 34 microns. The mean duration between PKP and
      first PTK was 85.1 months (range: 37-108 months). Two and three PTK procedures
      were done for seven and five eyes, respectively. Mean duration between first and
      second and second and third PTK was 62.12 +/- 34.41 and 42.8 +/- 13.54 months
      respectively. The average cut depth was 43.66 +/- 19.57, 75 +/- 43.30 and 39 +/-
      19.79 microns after the first, second and third PTK procedures, respectively. All
      eyes had a corneal haze. Pre first PTK mean BCVA was 20/200 and improved
      significantly after the first two PTK procedures to 20/40 and after the third PTK
      procedure to 20/32 (P < 0.001). Five eyes had hyperopia. One acute graft
      rejection was managed successfully at 5 months with medical therapy. CONCLUSION:
      Multiple PTK procedures can be performed safely with improved visual acuity in
      grafts without compromising graft survival.

PMID- 27050351
TI  - Systematic approach to managing vernal keratoconjunctivitis in clinical practice:
      Severity grading system and a treatment algorithm.
AB  - Vernal keratoconjunctivitis is an ocular allergy that is common in the pediatric
      age group. It is often chronic, severe, and nonresponsive to the available
      treatment options. Management of these children is difficult and often a dilemma
      for the practitioner. There is a need to simplify and standardize its management.
      To achieve this goal, we require a grading system to judge the severity of
      inflammation and an algorithm to select the appropriate medications. This article
      provides a simple and practically useful grading system and a stepladder
      algorithm for systematic treatment of these patients. Use of appropriate
      treatment modalities can reduce treatment and disease-related complications.

PMID- 27050352
TI  - Syphilitic uveitis as the presenting feature of HIV.

PMID- 27050353
TI  - Lightning injury of posterior segment of the eye.

PMID- 27050354
TI  - Multi-drug resistant Pseudomonas aeruginosa keratitis and its effective treatment
      with topical colistimethate.
AB  - The purpose was to evaluate the clinical outcome in multi-drug resistant
      Pseudomonas aeruginosa (MDR-PA) bacterial keratitis and report the successful use
      of an alternative antibiotic, topical colistimethate in some of them. The medical
      records of 12 culture-proven MDR-PA keratitis patients, all exhibiting in vitro
      resistance by Kirby-Bauer disc diffusion method to >= three classes of routinely
      used topical antibiotics were reviewed. Eight patients were treated with 0.3%
      ciprofloxacin or ofloxacin, 1 patient with 5% imipenem/cilastatin and 3 patients
      with 1.6% colistimethate. The outcomes in 8 eyes treated with only
      fluoroquinolones were evisceration in 4 eyes, therapeutic corneal graft in 1 eye,
      phthisis bulbi in 1 eye, and no improvement in 2 eyes. The eye treated with
      imipenem/cilastin required a therapeutic corneal graft. All the three eyes
      treated with 1.6% colistimethate healed. Colistimethate may prove to be an
      effective alternative antibiotic in the treatment of MDR-PA keratitis.

PMID- 27050355
TI  - Bilateral macular hemorrhage due to megaloblastic anemia: A rare case report.
AB  - We report a case of a 17-year-old female patient who presented with sudden,
      painless, nonprogressive diminished vision in both eyes (best corrected visual
      acuity in right eye - 6/60 and left eye - 6/36). An ophthalmological evaluation
      revealed bilateral pale tarsal conjunctiva and bilateral macular hemorrhage.
      Hematological evaluation revealed the presence of megalocytic anemia (with
      hemoglobin - 4.9 g%). General examination showed severe pallor. On systemic
      examination, no abnormality was detected, confirmed by ultrasonography abdomen.
      Other causes of severe anemia have been ruled out. Intraocular pressure in both
      eyes was 12 mmHg. This case documents the rare occurrence of bilateral
      subinternal limiting membrane macular hemorrhage with megaloblastic anemia
      without thrombocytopenia and other retinal features of anemic retinopathy. 

PMID- 27050356
TI  - Hyaluronidase hypersensitivity: A rare complication of peribulbar block.
AB  - Peribulbar block, though safe, can cause serious complications such as globe
      perforation and peribulbar hemorrhage. Hyaluronidase is an enzyme that is used as
      an adjuvant in peribulbar anesthesia, and it helps in rapid penetration of the
      anesthetic agent. Hypersensitivity to hyaluronidase is a rare but potentially
      sight-threatening complication. We report a case of hyaluronidase
      hypersensitivity following peribulbar injection for cataract surgery mimicking as
      peribulbar hematoma in the immediate postinjection phase and as orbital
      cellulitis 48 h later.

PMID- 27050357
TI  - Two cases of ultrathin Descemet stripping automated endothelial keratoplasty
      utilizing a graft that had undergone radial keratotomy.
AB  - This is a report of two cases in which tissue that had undergone radial
      keratotomy (RK) was utilized for double-pass ultrathin Descemet stripping
      automated endothelial keratoplasty (UT-DSAEK). Postoperative slit-lamp
      examination, visual acuity, anterior segment optical coherence tomography, and
      specular microscopy were available 30 months after surgery. Both corneas from a
      donor, who had undergone RK several years before his demise, and were otherwise
      suitable for endothelial keratoplasty were prepared for UT-DSAEK using double
      pass dissection using first a 300 mm microkeratome head and then a 130MUm
      microkeratome head (ALTK system, Moria, Antony, France). After the second cut,
      the tissue was punched to 9.0 mm and transplanted in two eyes with endothelial
      decompensation according to standard technique. As early as 3 months after
      surgery, both patients had 20/25 best-corrected visual acuity, which remained
      stable for the following 27 months. Postoperative endothelial cell loss was 34%
      and 57% at 2.5 years. In conclusion, post-RK donor tissue can be used for UT
      DSAEK.

PMID- 27050358
TI  - Macular hole formation and spontaneous closure following neodymium-doped yttrium
      aluminum garnet capsulotomy in a vitrectomized eye.

PMID- 27050359
TI  - Comment on: Traumatic central serous chorioretinopathy.

PMID- 27050360
TI  - A case of spontaneously resolved primary congenital glaucoma.

PMID- 27050361
TI  - Author reply.

PMID- 27050362
TI  - Management of Heavy Eyeball Syndrome--our experience.

PMID- 27050363
TI  - Traumatic central serous chorioretinopathy in the fellow eye.

PMID- 27050364
TI  - Handheld spectral domain optical coherence tomography seems to be a must-have
      device for future treatment methods of hereditary maculopathies.

PMID- 27050365
TI  - Tetraphenylethene-2-Pyrone Conjugate: Aggregation-Induced Emission Study and
      Explosives Sensor.
AB  - Design and synthesis of a novel tetraphenylethene-2-pyrone (TPEP) conjugate
      exhibiting donor-acceptor characteristics is reported. The localized frontier
      molecular orbitals (DFT studies) and the solvent polarity dependent
      photoluminescence characteristics directly corroborate the presence of
      intramolecular charge transfer character in TPEP. TPEP is poorly emissive in the
      solution state. In contrast, upon aggregation (THF/water mixtures), TPEP exhibits
      aggregation-induced emission enhancement. Upon aggregation, dyad TPEP forms a
      fluorescent nanoaggregate which was confirmed by transmission electron microscopy
      imaging studies. The luminescence nanoaggregates were elegantly exploited for
      selective detection of nitro aromatic compounds (NACs). It was found that
      nanoaggregates of TPEP were selectively sensing the picric acid over the other
      NACs. Efficiency of the quenching process was further evaluated by the Stern
      Volmer equation. TPEP-based low-cost fluorescent test strips were developed for
      the selective detection of picric acid.

PMID- 27050366
TI  - Cdc2-like kinase 2 is a key regulator of the cell cycle via FOXO3a/p27 in
      glioblastoma.
AB  - Cdc2-like kinase 2 (CLK2) is known as a regulator of RNA splicing that ultimately
      controls multiple physiological processes. However, the function of CLK2 in
      glioblastoma progression has not been described. Reverse-phase protein array
      (RPPA) was performed to identify proteins differentially expressed in CLK2
      knockdown cells compared to controls. The RPPA results indicated that CLK2
      knockdown influenced the expression of survival-, proliferation-, and cell cycle
      related proteins in GSCs. Thus, knockdown of CLK2 expression arrested the cell
      cycle at the G1 and S checkpoints in multiple GSC lines. Depletion of CLK2
      regulated the dephosphorylation of AKT and decreased phosphorylation of Forkhead
      box O3a (FOXO3a), which not only translocated to the nucleus but also increased
      p27 expression. In two glioblastoma xenograft models, the survival duration of
      mice with CLK2-knockdown GSCs was significantly longer than mice with control
      tumors. Additionally, tumor volumes were significantly smaller in CLK2-knockdown
      mice than in controls. Knockdown of CLK2 expression reduced the phosphorylation
      of FOXO3a and decreased Ki-67 in vivo. Finally, high expression of CLK2 protien
      was significantly associated with worse patient survival. These findings suggest
      that CLK2 plays a critical role in controlling the cell cycle and survival of
      glioblastoma via FOXO3a/p27. 

PMID- 27050367
TI  - Hepatitis B virus X protein up-regulates C4b-binding protein alpha through
      activating transcription factor Sp1 in protection of hepatoma cells from
      complement attack.
AB  - Hepatitis B virus X protein (HBx) plays crucial roles in the development of
      hepatocellular carcinoma (HCC). We previously showed that HBx protected hepatoma
      cells from complement attack by activation of CD59. Moreover, in this study we
      found that HBx protected hepatoma cells from complement attack by activation of
      C4b-binding protein alpha (C4BPalpha), a potent inhibitor of complement system.
      We observed that HBx were positively correlated with those of C4BPalpha in
      clinical HCC tissues. Mechanistically, HBx activated the promoter core region of
      C4BPalpha, located at -1199/-803nt, through binding to transcription factor Sp1.
      In addition, chromatin immunoprecipitation (ChIP) assays showed that HBx was able
      to bind to the promoter of C4BPalpha, which could be blocked by Sp1 silencing.
      Functionally, knockdown of C4BPalpha obviously increased the deposition of C5b-9,
      a complex of complement membrane attack, and remarkably abolished the HBx-induced
      resistance of hepatoma cells from complement attack in vitro and in vivo. Thus,
      we conclude that HBx up-regulates C4BPalpha through activating transcription
      factor Sp1 in protection of liver cancer cells from complement attack. Our
      finding provides new insights into the mechanism by which HBx enhances protection
      of hepatoma cells from complement attack. 

PMID- 27050368
TI  - MERS-CoV virus-like particles produced in insect cells induce specific humoural
      and cellular imminity in rhesus macaques.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory
      disease in humans with a case fatality rate of over 39%, and poses a considerable
      threat to public health. A lack of approved vaccine or drugs currently
      constitutes a roadblock in controlling disease outbreak and spread. In this
      study, we generated MERS-CoV VLPs using the baculovirus expression system.
      Electron microscopy and immunoelectron microscopy results demonstrate that MERS
      CoV VLPs are structurally similar to the native virus. Rhesus macaques inoculated
      with MERS-CoV VLPs and Alum adjuvant induced virus-neutralizing antibodies titers
      up to 1:40 and induced specific IgG antibodies against the receptor binding
      domain (RBD), with endpoint titers reaching 1:1,280. MERS-CoV VLPs also elicited
      T-helper 1 cell (Th1)-mediated immunity, as measured by ELISpot. These data
      demonstrate that MERS-CoV VLPs have excellent immunogenicity in rhesus macaques,
      and represent a promising vaccine candidate.

PMID- 27050369
TI  - Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: implications
      for prognosis.
AB  - To examine the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4)
      expression and esophageal carcinoma prognosis, CTLA-4 expression was
      immunohistochemically detected in paraffin-embedded primary tumor specimens from
      158 patients with esophageal cancer. CTLA-4 was detected in the cytoplasm and
      cell membranes of esophageal cancer cells and in interstitial lymphocytes. In
      univariate analyses (log-rank), higher interstitial CTLA-4+ lymphocyte density
      and higher tumor CTLA-4 expression were associated with shorter overall survival
      (OS). After controlling for age and clinical stage, multivariate analysis (Cox)
      found that tumor CTLA-4 expression was an independent predictor of shorter OS (HR
      2.016, P = 0.004). These results indicate that CTLA-4 expression in the tumor
      environment (both lymphocytes and tumor cells) is associated with poorer
      prognosis. In addition, CTLA-4 profiles may be useful for predicting the benefits
      and toxicity of CTLA-4 blockade in patients with esophageal carcinoma. 

PMID- 27050370
TI  - APE1 polymorphic variants cause persistent genomic stress and affect cancer cell
      proliferation.
AB  - Apurinic/apyrimidinic endonuclease 1 (APE1) is the main mammalian AP-endonuclease
      responsible for the repair of endogenous DNA damage through the base excision
      repair (BER) pathway. Molecular epidemiological studies have identified several
      genetic variants associated with human diseases, but a well-defined functional
      connection between mutations in APE1 and disease development is lacking. In order
      to understand the biological consequences of APE1 genetic mutations, we examined
      the molecular and cellular consequences of the selective expression of four non
      synonymous APE1 variants (L104R, R237C, D148E and D283G) in human cells. We found
      that D283G, L104R and R237C variants have reduced endonuclease activity and
      impaired ability to associate with XRCC1 and DNA polymerase beta, which are
      enzymes acting downstream of APE1 in the BER pathway. Complementation experiments
      performed in cells, where endogenous APE1 had been silenced by shRNA, showed that
      the expression of these variants resulted in increased phosphorylation of histone
      H2Ax and augmented levels of poly(ADP-ribosyl)ated (PAR) proteins. Persistent
      activation of DNA damage response markers was accompanied by growth defects
      likely due to combined apoptotic and autophagic processes. These phenotypes were
      observed in the absence of exogenous stressors, suggesting that chronic
      replication stress elicited by the BER defect may lead to a chronic activation of
      the DNA damage response. Hence, our data reinforce the concept that non
      synonymous APE1 variants present in the human population may act as cancer
      susceptibility alleles. 

PMID- 27050371
TI  - Inhibition of skeletal growth of human prostate cancer by the combination of
      docetaxel and BKM1644: an aminobisphosphonate derivative.
AB  - Bone metastasis is a major cause of prostate cancer (PCa) morbidity and
      mortality. Despite some success in transiently controlling clinical symptoms with
      docetaxel-based therapy, PCa patients become docetaxel-resistant and inevitably
      progress with no cure. We synthesized an acyl-tyrosine bisphosphonate amide
      derivative, BKM1644, with the intent of targeting bone metastatic PCa and
      enhancing docetaxel's efficacy. BKM1644 exhibits potent anti-cancer activity in
      the NCI-60 panel and effectively inhibits the proliferation of metastatic,
      castration-resistant PCa (mCRPC) cells, with IC50 ranging between 2.1 MUM and 6.3
      MUM. Significantly, BKM1644 sensitizes mCRPC cells to docetaxel treatment. Mice
      with pre-established C4-2 tumors in the tibia show a marked decrease in serum
      prostate-specific antigen (control: 173.72 +/- 37.52 ng/ml, combined treatment:
      64.45 +/- 22.19 ng/ml; p < 0.0001) and much improved bone architecture after
      treatment with the combined regimen. Mechanistic studies found that docetaxel
      temporarily but significantly increases survivin, an anti-apoptotic protein whose
      overexpression has been correlated with PCa bone metastasis and therapeutic
      resistance. Intriguingly, BKM1644 effectively inhibits survivin expression, which
      may antagonize docetaxel-induced survivin in bone metastatic PCa cells. Signal
      transducer and activator of transcription 3 (Stat3) may be involved in the
      suppression of survivin transcription by BKM1644, as confirmed by a survivin
      reporter assay. Collectively, these data indicate that BKM1644 could be a
      promising small-molecule agent to improve docetaxel efficacy and retard the bone
      metastatic growth of PCa. 

PMID- 27050372
TI  - Curcumin modulates chronic myelogenous leukemia exosomes composition and affects
      angiogenic phenotype via exosomal miR-21.
AB  - Tumor derived exosomes are vesicles which contain proteins and microRNAs that
      mediate cell-cell communication and are involved in angiogenesis and tumor
      progression. Curcumin derived from the plant Curcuma longa, shows anticancer
      effects. Exosomes released by CML cells treated with Curcumin contain a high
      amount of miR-21 that is shuttled into the endothelial cells in a biologically
      active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB
      expression and negatively modulated endothelial cells motility. We showed that
      the addition of CML control exosomes to HUVECs caused an increase in IL8 and
      VCAM1 levels, but Curcu-exosomes reversed these effects thus attenuating their
      angiogenic properties. This antiangiogenic effect was confirmed with in vitro and
      in vivo vascular network formation assays. SWATH analysis of the proteomic
      profile of Curcu-exosomes revealed that Curcumin treatment deeply changes their
      molecular properties, in particular, Curcumin induces a release of exosomes
      depleted in pro-angiogenic proteins and enriched in proteins endowed with anti
      angiogenic activity. Among the proteins differential expressed we focused on
      MARCKS, since it was the most modulated protein and a target of miR-21. Taken
      together our data indicated that also Curcumin attenuates the exosome's ability
      to promote the angiogenic phenotype and to modulate the endothelial barrier
      organization. 

PMID- 27050373
TI  - The role of glycogen synthase kinase-3beta (GSK-3beta) in endometrial carcinoma:
      A carcinogenesis, progression, prognosis, and target therapy marker.
AB  - PURPOSE: Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase
      involved in cancer development. Herein, we demonstrated the role of GSK-3beta in
      endometrial cancer (EC) and identified new therapeutic targets. RESULTS: GSK
      3beta was overexpressed in EC tissues, and was positively correlated with
      International Federation of Gynecology and Obstetrics (FIGO) staging,
      dedifferentiation, and myometrial infiltration depth. Besides, GSK-3beta
      overexpression predicted lower cumulative and relapse-free survival rate. si-GSK
      3beta transfection suppressed cell proliferation, migration, invasion, and
      promoted cell apoptosis through downregulating NF-kB, Cyclin D1 and MMP9
      expression whereas upregulating P21 expression. Bioinformatic predictions and
      dual-luciferase reporter assays showed that GSK-3beta was a possible target of
      miR-129. MiR-129 transfection reduced GSK-3beta expression, and exhibited the
      same trend as si-GSK-3beta transfection in cell function experiments. The nude
      mouse xenograft assay showed that miR-129 overexpression may suppress tumor
      growth through downregulating GSK-3beta expression. Further studies showed that
      AZD1080, a GSK-3beta inhibitor, could also inhibit EC cell proliferation,
      migration and invasion, while induced cell apoptosis through modulating relevant
      genes downstream of GSK-3beta signaling. EXPERIMENTAL DESIGN: GSK-3beta
      expression was determined in EC tissue and normal endometrial tissues by
      immunohistochemistry. After GSK-3beta down-regulation by si-GSK-3beta, microRNA
      129 mimic transfection or GSK-3beta inhibitor exposure, EC cell phenotypes and
      related molecules were examined. CONCLUSIONS: Our results demonstrate for the
      first time that GSK-3beta may be a novel and important therapeutic target for the
      treatment of endometrial carcinoma. GSK-3beta inhibitor AZD1080 may be an
      effective drug for treating endometrial carcinoma.

PMID- 27050374
TI  - Identification of galectin-1 as a novel mediator for chemoresistance in chronic
      myeloid leukemia cells.
AB  - Multidrug resistance protein-1 (MDR1) has been proven to be associated with the
      development of chemoresistance to imatinib (Glivec, STI571) which displays high
      efficacy in treatment of BCR-ABL-positive chronic myelogenous leukemia (CML).
      However, the possible mechanisms of MDR1 modulation in the process of the
      resistance development remain to be defined. Herein, galectin-1 was identified as
      a candidate modulator of MDR1 by proteomic analysis of a model system of leukemia
      cell lines with a gradual increase of MDR1 expression and drug resistance.
      Coincidently, alteration of galectin-1 expression triggers the change of MDR1
      expression as well as the resistance to the cytotoxic drugs, suggesting that
      augment of MDR1 expression engages in galectin-1-mediated chemoresistance.
      Moreover, we provided the first data showing that NF-kappaB translocation induced
      by P38 MAPK activation was responsible for the modulation effect of galectin-1 on
      MDR1 in the chronic myelogenous leukemia cells. Galectin-1 might be considered as
      a novel target for combined modality therapy for enhancing the efficacy of CML
      treatment with imatinib. 

PMID- 27050375
TI  - Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell
      carcinoma progression.
AB  - BACKGROUND: Storkhead box protein 2 (STOX2) is a transcriptional factor
      associated with pre-eclampsia with fetal growth restriction. We recently reported
      that melanoma inhibitory activity (MIA) promotes oral squamous cell carcinoma
      (OSCC) progression. However, the relationship between STOX2 and MIA remains
      unknown in malignancies. METHODS: We used immunohistochemistry and PCR to
      investigate MIA and STOX2 expression in OSCC. We also performed functional
      analysis in human OSCC cells. RESULTS: MIA and STOX2 mRNA levels were higher in
      OSCCs than in normal oral epithelial cells, and upregulation of STOX2 was
      significantly correlated with overexpression of MIA. Immunostaining for STOX2 was
      associated with nodal metastasis (P = 0.0002) and MIA expression (P < 0.0001).
      Furthermore, MIA expression (P = 0.0035) and STOX2 expression (P = 0.0061) were
      associated with poor outcome in OSCCs. In vitro analysis using OSCC cells
      revealed that MIA increased expression of STOX2 by paracrine manner. Moreover,
      STOX2 accelerated OSCC cell growth, invasion, suppressed apoptosis, and enhanced
      resistance to paclitaxel, cisplatin, and 5-FU. CONCLUSIONS: Our results suggest
      that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in
      OSCCs.

PMID- 27050376
TI  - Development of a prediction model for radiosensitivity using the expression
      values of genes and long non-coding RNAs.
AB  - Radiotherapy has become a popular and standard approach for treating cancer
      patients because it greatly improves patient survival. However, some of the
      patients receiving radiotherapy suffer from adverse effects and do not obtain
      survival benefits. This may be attributed to the fact that most radiation
      treatment plans are designed based on cancer type, without consideration of each
      individual's radiosensitivity. A model for predicting radiosensitivity would help
      to address this issue. In this study, the expression levels of both genes and
      long non-coding RNAs (lncRNAs) were used to build such a prediction model.
      Analysis of variance and Tukey's honest significant difference tests (P < 0.001)
      were utilized in immortalized B cells (GSE26835) to identify differentially
      expressed genes and lncRNAs after irradiation. A total of 41 genes and lncRNAs
      associated with radiation exposure were revealed by a network analysis algorithm.
      To develop a predictive model for radiosensitivity, the expression profiles of
      NCI-60 cell lines along, with their radiation parameters, were analyzed. A
      genetic algorithm was proposed to identify 20 predictors, and the support vector
      machine algorithm was used to evaluate their prediction performance. The model
      was applied to 2 datasets of glioblastoma, The Cancer Genome Atlas and GSE16011,
      and significantly better survival was observed in patients with greater predicted
      radiosensitivity. 

PMID- 27050377
TI  - ATG9A loss confers resistance to trastuzumab via c-Cbl mediated Her2 degradation.
AB  - Acquired or de novo resistance to trastuzumab remains a barrier to patient
      survival and mechanisms underlying this still remain unclear. Using stable
      isotope labelling by amino acids in cell culture (SILAC)-based quantitative
      proteomics to compare proteome profiles between trastuzumab sensitive/resistant
      cells, we identified autophagy related protein 9A (ATG9A) as a down-regulated
      protein in trastuzumab resistant cells (BT474-TR). Interestingly, ATG9A ectopic
      expression markedly decreased the proliferative ability of BT474-TR cells but not
      that of the parental line (BT474). This was accompanied by a reduction of Her2
      protein levels and AKT phosphorylation (S473), as well as a decrease in Her2
      stability, which was also observed in JIMT1 and MDA-453, naturally trastuzumab
      resistant cells. In addition, ATG9A indirectly promoted c-Cbl recruitment to Her2
      on T1112, a known c-Cbl docking site, leading to increased K63 Her2
      polyubiquitination. Whereas silencing c-Cbl abrogated ATG9A repressive effects on
      Her2 and downstream PI3K/AKT signaling, its depletion restored BT474-TR
      proliferative rate. Taken together, our findings show for this first time that
      ATG9A loss in trastuzumab resistant cells allowed Her2 to escape from lysosomal
      targeted degradation through K63 poly-ubiquitination via c-Cbl. This study
      identifies ATG9A as a potentially druggable target to overcome resistance to anti
      Her2 blockade. 

PMID- 27050379
TI  - Genetic variants of CHRNA5-A3 and CHRNB3-A6 predict survival of patients with
      advanced non-small cell lung cancer.
AB  - Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and
      progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two
      gene clusters encoding nAChR subunits, have been associated with lung cancer
      risk. In this study, we investigated whether variants in the two gene clusters
      were associated with prognosis of advanced non-small cell lung cancer (NSCLC). A
      total of 165 stage IIIB-IV NSCLC patients were enrolled in this study. Three
      polymorphisms (rs667282 and rs3743073 in CHRNA5-A3 and rs13280604 in CHRNB3-A6)
      were genotyped using the TaqMan method. Overall survival (OS) was estimated using
      the log-rank test and the Cox models. Our results showed that patients with
      CHRNA5-A3 rs667282 TT or TC genotypes had a significantly shorter OS than those
      carrying the CC genotype (Log-rank, P = 0.043). Furthermore, multivariate Cox
      regression analysis showed that rs667282 TT/TC genotypes are significantly
      associated with increased risk of overall deaths (adjusted hazard ratio, 1.7; 95%
      CI, 1.1-2.7). However, the similar results were not observed for other two
      polymorphisms. Furthermore, no evident association was found between these
      variants and clinicopathologic features of advanced NSCLC. Our present study
      suggested that rs667282 in CHRNA5-A3 may modify the prognosis of patients with
      advanced NSCLC. 

PMID- 27050378
TI  - Novel leptin OB3 peptide-induced signaling and progression in thyroid cancers:
      Comparison with leptin.
AB  - Obesity results in increased secretion of cytokines from adipose tissue and is a
      risk factor for various cancers. Leptin is largely produced by adipose tissue and
      cancer cells. It induces cell proliferation and may serve to induce various
      cancers. OB3-leptin peptide (OB3) is a new class of functional leptin peptide.
      However, its mitogenic effect has not been determined. In the present study,
      because of a close link between leptin and the hypothalamic-pituitary-thyroid
      axis, OB3 was compared with leptin in different thyroid cancer cells for gene
      expression, proliferation and invasion. Neither agent stimulated cell
      proliferation. Leptin stimulated cell invasion, but reduced adhesion in
      anaplastic thyroid cancer cells. Activated ERK1/2 and STAT3 contributed to leptin
      induced invasion. In contrast, OB3 did not affect expression of genes involved in
      proliferation and invasion. In vivo studies in the mouse showed that leptin, but
      not OB3, significantly increased circulating levels of thyrotropin (TSH), a
      growth factor for thyroid cancer. In summary, OB3 is a derivative of leptin that
      importantly lacks the mitogenic effects of leptin on thyroid cancer cells. 

PMID- 27050380
TI  - Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic
      Fracturing Fluids, Flowback, and Produced Waters.
AB  - Concerns have been raised about potential public health effects that may arise if
      hydraulic fracturing-related chemicals were to impact drinking water resources.
      This study presents an overview of the chronic oral toxicity values-specifically,
      chronic oral reference values (RfVs) for noncancer effects, and oral slope
      factors (OSFs) for cancer-that are available for a list of 1173 chemicals that
      the United States (U.S.) Environmental Protection Agency (EPA) identified as
      being associated with hydraulic fracturing, including 1076 chemicals used in
      hydraulic fracturing fluids and 134 chemicals detected in flowback or produced
      waters from hydraulically fractured wells. The EPA compiled RfVs and OSFs using
      six governmental and intergovernmental data sources. Ninety (8%) of the 1076
      chemicals reported in hydraulic fracturing fluids and 83 (62%) of the 134
      chemicals reported in flowback/produced water had a chronic oral RfV or OSF
      available from one or more of the six sources. Furthermore, of the 36 chemicals
      reported in hydraulic fracturing fluids in at least 10% of wells nationwide
      (identified from EPA's analysis of the FracFocus Chemical Disclosure Registry
      1.0), 8 chemicals (22%) had an available chronic oral RfV. The lack of chronic
      oral RfVs and OSFs for the majority of these chemicals highlights the significant
      knowledge gap that exists to assess the potential human health hazards associated
      with hydraulic fracturing.

PMID- 27050381
TI  - Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high-fat
      diet experimental rabbit animal model.
AB  - The etiology of metabolic syndrome (MetS) is complex and involves the interplay
      between environmental, lifestyle and genetic determinants. MetS in men can be
      associated with a biochemical pattern of partial hypogonadotropic hypogonadism
      (HH). A similar pattern has been noted in both men and women with a variety of
      acute illnesses and chronic diseases, and there is ongoing debate regarding
      whether this phenomenon might adaptive (e.g. diverting resources from
      reproduction into survival), or maladaptive (e.g. anemia, sarcopenia, osteopenia
      and fatigue of androgen-deficiency amplify and widen the adverse consequences of
      the original disease-trigger). In women with hypothalamic amenorrhea (HA-HH
      secondary to chronic bioenergetic deficit from dietary restriction and/or
      intensive exercise), a genetic link to congenital HH (CHH) was recently
      established; women carrying monoallelic CHH gene mutations will typically not
      develop CHH, but are significantly more susceptible to HA. However, the male
      reproductive axis seems to be more resistant to similar environmental insults. In
      contrast, MetS-associated HH (mHH) is specifically a male phenomenon; the
      reproductive phenotype of females with MetS tending instead towards
      hyperandrogenism, rather than hypogonadism. The underlying pathogenic mechanisms
      responsible for mHH have not been clearly identified and, as yet, there has been
      no investigation of a potential role for CHH mutation carriage in its etiology.
      Over the decades, the use of either genetic- or diet-induced obesity and/or MetS
      animal models has greatly helped to illuminate the complex etiology of metabolic
      dysregulation, but the strong relationship between obesity/MetS and mHH in males
      has been largely neglected, with little or no information about the regulation of
      reproductive function by metabolic factors under conditions of bioenergetic
      excess. However, the pathogenic link between MetS and HH in males has been
      recently investigated in an animal model of high fat diet (HFD)-induced MetS,
      which perfectly recapitulates the human phenotype. Interesting insights derived
      by these studies have added novel information about the causative role played by
      hypothalamic alterations driven by metabolic disturbances in mHH. In particular,
      it appears that HFD-induced inflammatory injury at the hypothalamic level
      negatively affects GnRH neuron content, with the reduction of circulating
      gonadotropins and sex hormones being related to MetS severity. 

PMID- 27050382
TI  - Neuroradiological findings in hypogonadotropic hypogonadism.
AB  - Hypogonadotropic hypogonadism (HH) is a clinical hallmark of a heterogeneous
      group of acquired and inherited diseases. Patients with HH undergo brain imaging
      in order to investigate morphological or signal abnormalities at the level of the
      hypothalamic-pituitary structures. The presence of tumors, lesions or atrophy
      might be the explanation of the hormone dysfunction. Nonetheless, in most
      patients both the hypothalamus and the pituitary gland appear normal. In some
      cases, the presence of ancillary, not necessarily HH-related brain abnormalities
      might provide significant clues on the underlying condition. We addressed those
      conditions associated with HH subdividing them into acquired or inherited
      diseases, highlighting the neuroradiologic features that might help in the
      diagnosis. 

PMID- 27050383
TI  - Metolachlor Sorption and Degradation in Soil Amended with Fresh and Aged
      Biochars.
AB  - Addition of organic amendments such as biochar to soils can influence pesticide
      sorption-desorption processes and, in turn, the amount of pesticide readily
      availability for transport and biodegradation. Sorption-desorption processes are
      affected by both the physical and chemical properties of soils and pesticides, as
      well as soil-pesticide contact time, or aging. Changes in sorption-desorption of
      metolachlor with aging in soil amended with three macadamia nut shell biochars
      aged 0 (BCmac-fr), 1 year (BCmac-1yr), and 2 years (BCmac-2yr) and two wood
      biochars aged 0 (BCwood-fr) and 5 years (BCwood-5yr) were determined. Apparent
      sorption coefficient (Kd-app) values increased with incubation time to a greater
      extent in amended soil as compared to unamended soils; Kd-app increased by 1.2
      fold for the unamended soil, 2.0-fold for BCwood-fr, 1.4-fold for BCwood-5yr, 2.4
      fold for BCmac-fr, 2.5-fold for BCmac-1yr, and 1.9-fold for BCmac-4yr. The
      increase in calculated Kd-app value was the result of a 15% decrease in the
      metolachlor solution concentration extractable with CaCl2 solution with
      incubation time in soil as compared to a 50% decrease in amended soil with very
      little change in the sorbed concentration. Differences could possibly be due to
      diffusion to less accessible or stronger binding sites with time, a faster rate
      of degradation (in solution and on labile sites) than desorption, or a
      combination of the two in the amended soils. These data show that transport
      models would overpredict the depth of movement of metolachlor in soil if effects
      of aging or biochar amendments are not considered. 

PMID- 27050384
TI  - Multicolor ELISA based on alkaline phosphatase-triggered growth of Au nanorods.
AB  - Seed-mediated synthesis of gold nanorods (AuNRs) has been widely used for diverse
      applications in the past decade. In this work, this synthetic process is
      demonstrated for multicolor biosensing for the first time. Our investigation
      reveals that ascorbic acid acts as a key factor to mediate the growth of AuNRs.
      This phenomenon is incorporated into the alkaline phosphatase (ALP)-enzyme-linked
      immunosorbent assay (ELISA) system based on the fact that ALP can catalyze the
      conversion of ascorbic acid-phosphate into ascorbic acid with high efficiency.
      This allows us to develop a multicolor ELISA approach for sensitive detection of
      disease biomarkers with the naked eye. We show the proof-of-concept multicolor
      ELISA for the detection of prostate-specific antigen (PSA) in human serum. The
      results show that different colors are presented in response to different
      concentrations of PSA, and a detection limit of 3 * 10(-15) g mL(-1) in human
      serum was achieved. The proposed multicolor ELISA could be a good supplement to
      conventional ELISA for POC diagnostics.

PMID- 27050385
TI  - Hypervalent iodine(iii)-promoted N-incorporation into N-aryl vinylogous
      carbamates to quinoxaline diesters: access to 1,4,5,8-tetraazaphenanthrene.
AB  - A novel oxidative N-incorporation strategy for synthesis of quinoxaline diesters
      under metal-free conditions is described for the first time. The mild reaction
      conditions allow for this transformation via the formation of two C(sp(2))-N
      bonds utilizing cheaply available NaN3 as the N-atom source. N-Aryl vinylogous
      carbamates in this study undergo azidation at enamino C(sp(2))-H selectively. The
      robustness of this strategy is further demonstrated by the synthesis of a
      valuable 1,4,5,8-tetraazaphenanthrene derivative using a mild and convenient
      approach. 

PMID- 27050386
TI  - Solvent-Dictated Lithium Sulfur Redox Reactions: An Operando UV-vis Spectroscopic
      Study.
AB  - Fundamental understanding of solvent's influence on Li-S redox reactions is
      required for rational design of electrolyte for Li-S batteries. Here we employ
      operando UV-vis spectroscopy to reveal that Li-S redox reactions in high-donor
      number solvents, for example, dimethyl sulfoxide (DMSO), undergo multiple
      electrochemical and chemical reactions involving S8(2-), S6(2-), S4(2-), and S3(*
      ), where S3(*-) is the most stable and dominant reaction intermediate. In low
      donor-number solvents, for example, 1,3-dioxolane:1,2-dimethoxyethane, the
      dominant reaction intermediate, is found to be S4(2-). The stability of these
      main polysulfide intermediates determines the reaction rates of the
      disproportionation/dissociation/recombination of polysulfides and thereby affects
      the reaction rates of the Li-S batteries. As an example, we show that
      dimethylformamide, a high-donor-number solvent, which exhibits stronger
      stabilization of S3(*-) compared with DMSO, significantly reduces Li-S cell
      polarization compared with DMSO. Our study reveals solvent-dependent Li-S
      reaction pathways and highlights the role of polysulfide stability in the
      efficiency of Li-S batteries. 

PMID- 27050387
TI  - Speeding Up Sigmatropic Shifts-To Halve or to Hold.
AB  - Catalysis is common. Rational catalyst design, however, is at the frontier of
      chemical science. Although the histories of physical organic and synthetic
      organic chemistry boast key chapters involving [3s,3s] sigmatropic shifts,
      catalysis of these reactions is much less common than catalysis of ostensibly
      more complex processes. The comparative dearth of catalysts for sigmatropic
      shifts is perhaps a result of the perception that transition state structures for
      these reactions, like their reactants, are nonpolar and therefore not amenable to
      selective stabilization and its associated barrier lowering. However, as
      demonstrated in this Account, transition state structures for [3s,3s] sigmatropic
      shifts can in fact have charge distributions that differ significantly from those
      of reactants, even for hydrocarbon substrates, allowing for barriers to be
      decreased and rates increased. In some cases, differences in charge distribution
      result from the inclusion of heteroatoms at specific positions in reactants, but
      in other cases differences are actually induced by catalysts. Perhaps
      surprisingly, strategies for complexation of transition state structures that
      remain nonpolar are also possible. In general, the strategies for catalysis
      employed can be characterized as involving either mechanistic intervention, where
      a catalyst induces a change from the concerted mechanism expected for a [3s,3s]
      sigmatropic shift to a multistep process (cutting the transformation into halves
      or smaller pieces) whose overall barrier is decreased relative to the concerted
      process, or transition state complexation, where a catalyst simply binds (holds)
      more tightly to the transition state structure for a [3s,3s] sigmatropic shift
      than to the reactant, leading to a lower barrier in the presence of the catalyst.
      Both of these strategies can be considered to be biomimetic in that enzymes
      frequently induce multistep processes and utilize selective transition state
      stabilization for the steps involved. In addition, transition state complexation
      was the principle around which catalytic antibodies were originally designed. The
      field of catalysis of sigmatropic shifts is now ready for rational design. The
      studies described here all provide evidence for the origins of rate acceleration,
      derived in large part from the results of quantum chemical calculations, that can
      now be applied to the design of new catalysts for [3s,3s] and other sigmatropic
      shifts. 

PMID- 27050388
TI  - Impact of Ser17 Phosphorylation on the Conformational Dynamics of the Oncoprotein
      MDM2.
AB  - MDM2 is an important oncoprotein that downregulates the activity of the tumor
      suppressor protein p53 via binding of its N-terminal domain to the p53
      transactivation domain. The first 24 residues of the MDM2 N-terminal domain form
      an intrinsically disordered "lid" region that interconverts on a millisecond time
      scale between "open" and "closed" states in unliganded MDM2. While the former
      conformational state is expected to facilitate p53 binding, the latter competes
      in a pseudo-substrate manner with p53 for its binding site. Phosphorylation of
      serine 17 in the MDM2 lid region is thought to modulate the equilibrium between
      "open" and "closed" lid states, but contradictory findings on the favored lid
      conformational state upon phosphorylation have been reported. Here, the nature of
      the conformational states of MDM2 pSer17 and Ser17Asp variants was addressed by
      means of enhanced sampling molecular dynamics simulations. Detailed analyses of
      the computed lid conformational ensembles indicate that both lid variants
      stabilize a "closed" state, with respect to wild type. Nevertheless, the nature
      of the closed-state conformational ensembles differs significantly between the
      pSer17 and Ser17Asp variants. Thus, care should be applied in the interpretation
      of biochemical experiments that use phosphomimetic variants to model the effects
      of phosphorylation on the structure and dynamics of this disordered protein
      region.

PMID- 27050389
TI  - Deliberate self-harm among younger and older adults.
AB  - This study examined self-harming behaviors among younger and older adults who
      completed the Self-Harm Inventory (SHI). A 2 (age group) * 2 (gender) analysis of
      variance showed a significant main effect for age such that younger adult
      students (M = 3.42, SD = 3.86) had higher SHI total scores than community
      dwelling older adults (M = 1.58, SD = 2.35). Younger adults endorsed "Yes"
      responses significantly more frequently than older adults on 13 of 22 items.
      Future research should examine specific behaviors of older adults who self-harm
      more frequently and explore relationships between self-harming behaviors and
      other risk and resiliency factors for elder suicide.

PMID- 27050390
TI  - MnFe2O4@C Nanofibers as High-Performance Anode for Sodium-Ion Batteries.
AB  - MnFe2O4 nanodots (~3.3 nm) homogeneously dispersed in porous nitrogen-doped
      carbon nanofibers (denoted as MFO@C) were prepared by a feasible electrospinning
      technique. Meanwhile, MFO@C with the character of flexible free-standing membrane
      was directly used as binder- and current collector-free anode for sodium-ion
      batteries, exhibiting high electrochemical performance with high-rate capability
      (305 mA h g(-1) at 10000 mA g(-1) in comparison of 504 mA h g(-1) at 100 mA g(
      1)) and ultralong cycling life (ca. 90% capacity retention after 4200 cycles).
      The Na-storage mechanism was systematically studied, revealing that MnFe2O4 is
      converted into metallic Mn and Fe after the first discharge (MnFe2O4 + 8Na(+) +
      8e(-) -> Mn + 2Fe + 4Na2O) and then to MnO and Fe2O3 during the following charge
      (Mn + 2Fe + 4Na2O -> MnO + Fe2O3 + 8Na(+) + 8e(-)). The subsequent cycles occur
      through reversible redox reactions of MnO + Fe2O3 + 8Na(+) + 8e(-) <-> Mn + 2Fe +
      4Na2O, of which the reduction/oxidation of MnO/Mn takes place at a lower
      potential than that of Fe2O3/Fe. Furthermore, a soft package sodium-ion full
      battery with MFO@C anode and Na3V2(PO4)2F3/C cathode was assembled, delivering a
      stable capacity of ~400 mA h g(-1) for MFO@C (with 100 cycles at 500 mA g(-1))
      and a promising energy density of 77.8 Wh kg(-1) for the whole battery. This is
      owing to the distinctive structure of very-fine MnFe2O4 nanodots embedded in
      porous N-doped carbon nanofibers, which effectively improves the utilization rate
      of active materials, facilitates the transportation of electrons and Na(+) ions,
      and prevents the particle pulverization/agglomeration upon prolonged cycling.

PMID- 27050391
TI  - Rac1 modulates the formation of primordial follicles by facilitating STAT3
      directed Jagged1, GDF9 and BMP15 transcription in mice.
AB  - The size of the primordial follicle pool determines the reproductive potential of
      mammalian females, and establishment of the pool is highly dependent on specific
      genes expression. However, the molecular mechanisms by which the essential genes
      are regulated coordinately to ensure primordial follicle assembly remain a
      mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in
      controlling the formation of primordial follicles in mouse ovary. Employing fetal
      mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded
      the breakdown of germline cell cysts while Rac1 overexpression accelerated the
      formation of primordial follicles. In addition, in vivo inhibitor injection
      resulted in the formation of multi-oocyte follicles. Subsequent investigation
      showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn,
      nuclear STAT3 directly activated the transcription of essential oocyte-specific
      genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15
      regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells.
      Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect
      of Rac1 disruption, but also accelerated primordial follicle formation via Notch2
      signaling activation. Collectively, these results indicate that Rac1 plays
      important roles as a key regulator in follicular assembly.

PMID- 27050392
TI  - Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth
      by sponging multiple miRNAs.
AB  - Circular RNAs (circRNAs) represent a class of widespread and diverse endogenous
      RNAs that may regulate gene expression in eukaryotes. However, the regulation and
      function of human circRNAs remain largely unknown. Here we generate ribosomal
      depleted RNA sequencing data from six normal tissues and seven cancers, and
      detect at least 27,000 circRNA candidates. Many of these circRNAs are differently
      expressed between the normal and cancerous tissues. We further characterize one
      abundant circRNA derived from Exon2 of the HIPK3 gene, termed circHIPK3. The
      silencing of circHIPK3 but not HIPK3 mRNA significantly inhibits human cell
      growth. Via a luciferase screening assay, circHIPK3 is observed to sponge to 9
      miRNAs with 18 potential binding sites. Specifically, we show that circHIPK3
      directly binds to miR-124 and inhibits miR-124 activity. Our results provide
      evidence that circular RNA produced from precursor mRNA may have a regulatory
      role in human cells. 

PMID- 27050393
TI  - A Transporter Interactome Is Essential for the Acquisition of Antimicrobial
      Resistance to Antibiotics.
AB  - Awareness of the problem of antimicrobial resistance (AMR) has escalated and drug
      resistant infections are named among the most urgent problems facing clinicians
      today. Our experiments here identify a transporter interactome and portray its
      essential function in acquisition of antimicrobial resistance. By exposing E.
      coli cells to consecutive increasing concentrations of the fluoroquinolone
      norfloxacin we generated in the laboratory highly resistant strains that carry
      multiple mutations, most of them identical to those identified in clinical
      isolates. With this experimental paradigm, we show that the MDTs function in a
      coordinated mode to provide an essential first-line defense mechanism, preventing
      the drug reaching lethal concentrations, until a number of stable efficient
      alterations occur that allow survival. Single-component efflux transporters
      remove the toxic compounds from the cytoplasm to the periplasmic space where TolC
      dependent transporters expel them from the cell. We postulate a close interaction
      between the two types of transporters to prevent rapid leak of the hydrophobic
      substrates back into the cell. The findings change the prevalent concept that in
      Gram-negative bacteria a single multidrug transporter, AcrAB-TolC type, is
      responsible for the resistance. The concept of a functional interactome, the
      process of identification of its members, the elucidation of the nature of the
      interactions and its role in cell physiology will change the existing paradigms
      in the field. We anticipate that our work will have an impact on the present
      strategy searching for inhibitors of AcrAB-TolC as adjuvants of existing
      antibiotics and provide novel targets for this urgent undertaking. 

PMID- 27050395
TI  - Influence of different surfactants on the physicochemical properties of elastic
      liposomes.
AB  - Elastic liposomes are capable to improve drug transport through the skin by
      acting as penetration enhancers due to the high fluidity and elasticity of the
      liposome membranes. Therefore, elastic liposomes were prepared and characterized
      to facilitate the transdermal transport of bioactive molecules. Liposomes
      consisted of dimyristoylphosphatidylcholine (DMPC) as the structural component,
      with different surfactants derived from lauric acid as elastic components: C12E5
      (polyoxyethylene-5-lauryl ether), PEG4L (polyethyleneglycol-4-lauryl ester),
      PEG4DL (polyethylene glycol-4-dilauryl ester), PEG8L (polyethylene glycol-8
      lauryl ester) and PEG8DL (polyethylene glycol-8-dilauryl ester). The elastic
      liposomes were characterized in terms of their phospholipid content, mean
      diameter, size distribution, elasticity and stability during storage, as well as
      their ability to incorporate surfactant and permeate through 50 nm pore size
      membranes. The results showed that the phospholipid phase transition temperature,
      the fluidity of the lipid bilayer resulting from incorporation of the surfactant
      and the preservation of particle integrity were factors determining the
      performance of the elastic liposomes in permeating through nanoporous membranes.
      The best results were obtained using DMPC combined with the surfactants PEG8L or
      PEG8DL. The findings demonstrate the potential of using elastic liposomes for
      transdermal administration of drugs.

PMID- 27050396
TI  - Researching Complex Interventions in Health: The State of the Art : Exeter, UK.
      14-15 October 2015.

PMID- 27050397
TI  - What Residents Say About Communicating with Patients: A Preliminary Examination
      of Doctor-to-Doctor Interaction.
AB  - This article describes the implementation and initial assessment of a training
      blog created within a family medicine department and used as a feedback mechanism
      for residents. First-year residents (n = 7) at a large private East Coast
      university hospital had an interaction with a patient recorded and posted to a
      training blog. The residents then watched this, and posted a reaction to their
      interaction with the patient. Within this reaction the residents offered self
      reflection on the experience and were provided an opportunity to solicit advice
      from their colleagues to improve their communicative strategies and style. Once
      the reaction was posted to the blog, other residents watched the videotaped
      interaction, read the self-assessment written by the resident, and responded as
      part of their communication training. Content analysis of the messages suggests
      that the residents are socially skilled. They offer each other advice, provide
      each other with emotional and esteem social support, and use techniques such as
      self-deprecation in what appears to be a strategic manner. Perhaps most
      interesting is that they tend to identify the problems and difficulties they
      experience during patient-physician interactions in an apparent effort to deflect
      responsibility from the practicing physician. Patient challenges raised by
      residents included talkativeness, noncompliance, health literacy, and situational
      constraints.

PMID- 27050398
TI  - Modifications of the 7-Hydroxyl Group of the Transthyretin Ligand Luteolin
      Provide Mechanistic Insights into Its Binding Properties and High Plasma
      Specificity.
AB  - Amyloid formation of the plasma protein transthyretin (TTR) has been linked to
      familial amyloid polyneuropathy and senile systemic amyloidosis. Binding of
      ligands within its natural hormone binding site can stabilize the tetrameric
      structure and impair amyloid formation. We have recently shown that the flavonoid
      luteolin stabilizes TTR in human plasma with a very high selectivity. Luteolin,
      however, is inactivated in vivo via glucuronidation for which the preferred site
      is the hydroxy group at position 7 on its aromatic A-ring. We have evaluated the
      properties of two luteolin variants in which the 7-hydroxy group has been
      exchanged for a chlorine (7-Cl-Lut) or a methoxy group (7-MeO-Lut). Using an in
      vitro model, based on human liver microsomes, we verified that these
      modifications increase the persistence of the drug. Crystal structure
      determinations show that 7-Cl-Lut binds similarly to luteolin. The larger MeO
      substituent cannot be accommodated within the same space as the chlorine or
      hydroxy group and as a result 7-MeO-Lut binds in the opposite direction with the
      methoxy group in position 7 facing the solvent. Both 7-Cl-Lut and 7-MeO-Lut
      qualify as high-affinity binders, but in contrast to luteolin, they display a
      highly non-specific binding to other plasma components. The binding of the two
      conformations and the key-interactions to TTR are discussed in detail. Taken
      together, these results show a proof-of-concept that the persistence of luteolin
      towards enzymatic modification can be increased. We reveal two alternative high
      affinity binding modes of luteolin to TTR and that modification in position 7 is
      restricted only to small substituents if the original orientation of luteolin
      should be preserved. In addition, the present work provides a general and
      convenient method to evaluate the efficacy of TTR-stabilizing drugs under
      conditions similar to an in vivo environment. 

PMID- 27050399
TI  - Azole susceptibility in clinical and environmental isolates of Aspergillus
      fumigatus from eastern Hokkaido, Japan.
AB  - Azole antifungals are used not only clinically for fungal infections but also
      used as agricultural fungicides. Recently, azole-resistant Aspergillus fumigatus
      containing a tandem repeat in the promoter region of cyp51A combined with amino
      acid substitution(s) appears in the environment in Eurasia, especially in several
      European countries. Although azole fungicides have been used in Japan, especially
      in Hokkaido, surveillance and characterization of A. fumigatus in Hokkaido have
      not been reported. In this study, we collected soil samples from farms that used
      an azole fungicide in the Tokachi area of eastern Hokkaido, isolated 91 A.
      fumigatus strains, and determined the minimal inhibitory concentrations of
      medical azoles required for these strains. Moreover, because causative agent A.
      fumigatus is ubiquitous in the air and acquired from the environment, we
      collected 22 clinical isolates of A. fumigatus to measure their susceptibility to
      medical azoles in a hospital in the Tokachi area. Our data show that almost all
      A. fumigatus isolates retained susceptibility to medical azoles. Clinical
      isolates OKH34 and OKH6 showed 8 and 2 MUg/mL of voriconazole, respectively, as
      the minimal inhibitory concentration. Both isolates did not contain tandem repeat
      in cyp51A promoter region. An isolate contained G448S mutation in cyp51A
      conferring voriconazole resistance, which is the first report from Japan. Our
      data shows the existence of azole-resistant and low azole-susceptible clinical
      isolates and highlight the necessity for continuous surveillance in Japan because
      resistant A. fumigatus strains can arise through clinical or environmental
      selection or could be introduced from overseas. 

PMID- 27050400
TI  - Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in
      Late Shang at Anyang, China.
AB  - Through the analysis of human skeletal remains and mortuary practice in Yinxu,
      this study investigates the impact of early urbanization on the commoners during
      the Late Shang dynasty (ca. 1250-1046 B.C.). A total of 347 individuals examined
      in this study represent non-elites who were recovered from two different burial
      contexts (formally buried in lineage cemeteries and randomly scattered in refuse
      pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia
      (childhood stress and frailty) and osteoperiostitis (adult stress) were examined
      to assess systemic stress exposure. Our results reveal that there was no
      significant difference in the frequency of enamel hypoplasia between two burial
      groups and between sexes, suggesting these urban commoners experienced similar
      stresses during childhood, but significantly elevated levels of cribra orbitalia
      and osteoperiostitis were observed in the refuse pit female cohort.
      Theoretically, urbanization would have resulted in increased population density
      in the urban centre, declining sanitary conditions, and increased risk of
      resource shortage. Biologically, children would be more vulnerable to such
      physiological disturbance; as a result, high percentages of enamel hypoplasia
      (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin
      commoners. Adults continued to suffer from stress, resulting in high frequencies
      of osteoperiostitis (40.0% total adults); in particular, in the refuse pit
      females who may also reflect a compound impact of gender inequality. Our data
      show that the non-elite urban population in the capital city of Late Shang
      Dynasty had experienced extensive stress exposure due to early urbanization with
      further social stratification only worsening the situation, and eventually
      contributing to collapse of the Shang Dynasty. 

PMID- 27050401
TI  - Usefulness of a Tailored eHealth Service for Informal Caregivers and
      Professionals in the Dementia Treatment and Care Setting: The eHealthMonitor
      Dementia Portal.
AB  - BACKGROUND: The European eHealthMonitor project (eHM) developed a user-sensitive
      and interactive Web portal for the dementia care setting called the eHM Dementia
      Portal (eHM-DP). It aims to provide targeted support for informal caregivers of
      persons with dementia and professionals. OBJECTIVE: The objective of this study
      was to assess the usefulness and impact of the eHM-DP service in the dementia
      care setting from two user perspectives: informal caregivers and professionals.
      METHODS: The evaluation study was conducted from June to September 2014 and
      followed a before-after, user-participatory, mixed-method design with
      questionnaires and interviews. The used intervention was the eHM-DP: an
      interactive Web portal for informal caregivers and professionals that was tested
      for a 12-week period. Primary outcomes for caregivers included empowerment,
      quality of life, caregiver burden, decision aid, as well as perceived usefulness
      and benefits of the eHM-DP. Primary outcomes for professionals involved decision
      aid, perceived usefulness, and benefits of the eHM-DP. RESULTS: A total of 25
      informal caregivers and 6 professionals used the eHM-DP over the 12-week study
      period. Both professionals and informal caregivers indicated perceived benefits
      and support by the eHM-DP. In total, 65% (16/25) of informal caregivers would use
      the eHM-DP if they had access to it. Major perceived benefits were individualized
      information acquisition, improved interaction between informal caregivers and
      professionals, access to support from home, and empowerment in health-related
      decisions (PrepDM Score: 67.9). Professionals highlighted the improved treatment
      and care over the disease course (83%, 5/6) and improved health care access for
      people living in rural areas (67%, 4/6). However, there was no improvement in
      caregiver burden (Burden Scale for Family Caregivers) and quality of life
      (EuroQol-5D-5L) over the study period. CONCLUSIONS: Our study provides insight
      into the different user perspectives on an eHealth support service in the
      dementia treatment and care setting. These results are of importance for future
      developments and the uptake of eHealth solutions in the dementia domain and
      reinforce the importance of early user involvement. Turning to the primary target
      of the eHM-DP service, our findings suggest that the eHM-DP service proved to be
      a valuable post-diagnostic support service, in particular for the home-based care
      setting. Further research on a larger scale is needed to enhance the
      implementation in existing health care infrastructures.

PMID- 27050402
TI  - Retrospective analysis of 3 different antithrombotic prophylaxis regimens in
      bariatric surgery.
AB  - BACKGROUND: The optimal amount of thromboembolic prophylaxis to use in bariatric
      surgery is still unresolved. OBJECTIVE: The aim of this study was to determine
      the optimal pharmacologic prophylaxis with minimal bleeding complications for
      bariatric patients. SETTING: A nonrandomized clinical study of 400 consecutive
      bariatric patients surgically treated between 2008 and 2013 at Peijas Hospital.
      METHODS: The patients, who either underwent mainly a sleeve gastrectomy or a Roux
      en-Y gastric bypass, were divided consecutively into 3 subgroups with different
      approaches to pharmacologic enoxaparin prophylaxis. For the first 100 operated
      patients (high-dose group), enoxaparin was given at a dose of 40 mg twice daily,
      starting 1 day before the operation. The next 100 patients (intermediate-dose
      group) received 40 mg of enoxaparin twice daily, without the dose on the morning
      of the operation. The last 200 patients (low-dose group) received enoxaparin 40
      mg once daily, starting 1 day before the operation and without the dose on the
      morning of the operation. The primary endpoints in this study were a major
      bleeding complication and a venous thromboembolism. RESULTS: There were no
      thromboembolic complications in this study. The difference in bleeding
      complications between the high-dose group and low-dose group was -10.5% (95% CI
      from -18.1% to -3.0%), and the difference between high-dose group and
      intermediate-dose group was -9% (95% CI from -17.4% to -.6%). Age and
      preoperative weight had no effect on bleeding complications, but hypertension
      significantly increased the amount of bleeding complications (P = .01, 95% CI
      from 1.55% to 29.7%). CONCLUSION: Thromboembolic complications are avoidable.
      Enoxaparin (40 mg) given once daily was the safest with regard to bleeding
      complications. High blood pressure elevates the risk for bleeding.

PMID- 27050403
TI  - Pancreatitis and intragastric balloon insertion.

PMID- 27050404
TI  - Lipids and bariatric procedures Part 2 of 2: scientific statement from the
      American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid
      Association (NLA), and Obesity Medicine Association (OMA).
AB  - Bariatric procedures generally improve dyslipidemia, sometimes substantially so.
      Bariatric procedures also improve other major cardiovascular risk factors. This 2
      part Scientific Statement examines the lipid effects of bariatric procedures and
      reflects contributions from authors representing the American Society for
      Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA),
      and the Obesity Medicine Association (OMA). Part 1 was published in the Journal
      of Clinical Lipidology, and reviewed the impact of bariatric procedures upon
      adipose tissue endocrine and immune factors, adipose tissue lipid metabolism, as
      well as the lipid effects of bariatric procedures relative to bile acids and
      intestinal microbiota. This Part 2 reviews: (1) the importance of nutrients
      (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the
      effects of bariatric procedures on gut hormones and lipid levels; (3) the effects
      of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors;
      (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric
      procedures on CVD; and finally, (6) the potential lipid effects of vitamin,
      mineral, and trace element deficiencies, that may occur after bariatric
      procedures. 

PMID- 27050405
TI  - Reply to comment on: Anastomotic techniques in open Roux-en-Y gastric bypass
      Primary open surgery and converted procedures.

PMID- 27050406
TI  - Segmental reversible ischemia of the liver after laparoscopic Roux-en-Y gastric
      bypass.

PMID- 27050407
TI  - Long-chain polyunsaturated fatty acid biosynthesis in the euryhaline herbivorous
      teleost Scatophagus argus: Functional characterization, tissue expression and
      nutritional regulation of two fatty acyl elongases.
AB  - Both the spotted scat Scatophagus argus and rabbitfish Siganus canaliculatus
      belong to the few cultured herbivorous marine teleost, however, their fatty acyl
      desaturase (Fad) system involved in long-chain polyunsaturated fatty acid (LC
      PUFA) biosynthesis is different. The S. argus has a ?6 Fad, while the rabbitfish
      has ?4 and ?6/?5 Fads, which were the first report in vertebrate and marine
      teleost, respectively. In order to compare the characteristics of elongases of
      very long-chain fatty acids (Elovl) between them, two Elovl cDNAs were cloned
      from S. argus in the present study. One has 885bp of open read fragment (ORF)
      encoding a protein with 294 amino acid (aa) showing Elovl5 activity functionally
      characterized by heterologous expression in yeast, which was primarily active for
      the elongation of C18 and C20 PUFAs. The other has 915bp of ORF coding for a 305
      aa protein showing Elovl4 activity, which was more efficient in the elongation of
      C20 and C22 PUFAs. Tissue distribution analyses by RT-PCR showed that elovl5 was
      highly expressed in the liver compared to other tissues determined, whereas
      elovl4 transcripts were only detected in the eye. The expression of elovl5 and
      elovl4 were significantly affected by dietary fatty acid composition, with
      highest expression of mRNA in the liver and eye of fish fed a diet with an 18:3n
      3/18:2n-6 ratio of 1.7:1. These results indicated that the S. argus has a similar
      Elovl system in the LC-PUFA biosynthetic pathway to that of rabbitfish although
      their Fad system was different, suggesting that the diversification of fish LC
      PUFA biosynthesis specificities is more associated with its Fad system. These new
      insights expand our knowledge and understanding of the molecular basis and
      regulation of LC-PUFA biosynthesis in fish. 

PMID- 27050408
TI  - Optimizing application parameters for lactic acid and sodium metasilicate against
      pathogens on fresh beef, pork and deli meats.
AB  - Lactic acid (LA) and sodium metasilicate (SM) have been approved for use as
      antimicrobials on meat. The objectives were to determine optimum concentrations,
      temperatures and hot-water dips of LA and SM for reduction of Escherichia coli
      O157:H7, non-O157 Shiga-toxin producing E. coli (STEC), Salmonella spp., and
      Listeria monocytogenes on beef, pork and deli meats. LA was applied at 1, 2, 3,
      and 4% and SM was applied at 2, 3, 4, and 5%. SM4 and LA4 were the lowest
      concentrations most effective against all pathogens. LA4 and SM4, the combination
      of the two (LASM), and distilled water control were applied at 4, 25, and 60
      degrees C. Temperature of application had no effect on pathogens. LA or SM alone
      were more effective in reduction of pathogens than LASM. Regardless of anti
      microbial used in post-packaging lethality treatments, there were no differences
      in L. monocytogenes. Treating deli meats with LA or SM did not reduce L.
      monocytogenes. Both LA and SM can be applied to fresh beef and pork to decrease
      pathogens. 

PMID- 27050409
TI  - Association of NLK polymorphisms with intramuscular fat content and fatty acid
      composition traits in pigs.
AB  - Nemo-like protein kinase (NLK) is a key enzyme in the noncanonical Wnt signaling
      pathway and it is involved in adipogenesis. In this study, the associations of
      the polymorphisms of the NLK gene with intramuscular fat (IMF) content and fatty
      acid (FA) composition traits were analyzed in crossbred commercial pigs. Three
      single nucleotide polymorphisms (SNPs) of the porcine NLK gene were identified in
      5'-flanking region and introns, consisting of g.403739_403764insdel, g.574462T>C
      and g.630426A>G. The NLK g.403739_403764insdel was significantly associated with
      IMF content and palmitoleic acid levels. No association of the NLK g.574462T>C
      SNP with IMF content was observed. However, this SNP was significantly associated
      with arachidic and eicosenoic acid levels. Moreover, the NLK g.630426A>G SNP was
      significantly associated with IMF content and the fatty composition of arachidic,
      linoleic, as well as polyunsaturated FA and omega6 FA levels. These results
      indicate the importance of porcine NLK as a candidate gene for porcine IMF
      content and fatty acid composition traits. 

PMID- 27050410
TI  - The Trypanosoma cruzi Diamine Transporter Is Essential for Robust Infection of
      Mammalian Cells.
AB  - Trypanosoma cruzi is incapable of synthesizing putrescine or cadaverine de novo,
      and, therefore, salvage of polyamines from the host milieu is an obligatory
      nutritional function for the parasite. A high-affinity diamine transporter
      (TcPOT1) from T. cruzi has been identified previously that recognizes both
      putrescine and cadaverine as ligands. In order to assess the functional role of
      TcPOT1 in intact parasites, a Deltatcpot1 null mutant was constructed by targeted
      gene replacement and characterized. The Deltatcpot1 mutant lacked high-affinity
      putrescine-cadaverine transport capability but retained the capacity to transport
      diamines via a non-saturable, low-affinity mechanism. Transport of spermidine and
      arginine was not impacted by the Deltatcpot1 lesion. The Deltatcpot1 cell line
      exhibited a significant but not total defect in its ability to subsist in Vero
      cells, although initial infection rates were not affected by the lesion. These
      findings reveal that TcPOT1 is the sole high-affinity diamine permease in T.
      cruzi, that genetic obliteration of TcPOT1 impairs the ability of the parasite to
      maintain a robust infection in mammalian cells, and that a secondary low-affinity
      uptake mechanism for this key parasite nutrient is operative but insufficient for
      optimal infection. 

PMID- 27050412
TI  - The Toxic Food Environment Around Elementary Schools and Childhood Obesity in
      Mexican Cities.
AB  - INTRODUCTION: The childhood obesity epidemic is a global concern. There is
      limited evidence in Mexico linking the local food environment to obesity. The
      purpose of this study is to describe the links between the local food environment
      around elementary schools and schoolchildren's BMI in two Mexican cities.
      METHODS: Cross-sectional surveys were conducted in 60 elementary schools in two
      Mexican cities (i.e., Cuernavaca and Guadalajara) in 2012-2013. Anthropometric
      measurements on schoolchildren were collected, as well as environmental direct
      audits and observations in a 100-m buffer around schools. Children's BMI was
      evaluated according to WHO-recommended procedures. In BMI models, the explanatory
      variable was the number of retail food sources. These models were adjusted for
      child's characteristics, schools' socioeconomic background, compliance with
      federal guidelines concerning unhealthy foods within schools' facilities, and
      corresponding city. Analysis was conducted in 2014. RESULTS: The number of mobile
      food vendors was higher around public schools than outside private schools
      (p<0.05). Linear regression procedures showed a significant positive statistical
      association between children's BMI and the number of mobile food vendors around
      schools. Schoolchildren from the highest tertile of mobile food vendors showed
      6.8% higher BMI units than those from the lowest tertile. Children attending
      schools within the highest tertile of food stores also had 4.7% higher BMI units
      than children from schools in the lowest tertile. CONCLUSIONS: Health policy in
      Mexico should target the obesogenic environment surrounding elementary schools,
      where children may be more exposed to unhealthy foods.

PMID- 27050411
TI  - Identification of Differentially Expressed Genes through Integrated Study of
      Alzheimer's Disease Affected Brain Regions.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia in older
      adults that damages the brain and results in impaired memory, thinking and
      behaviour. The identification of differentially expressed genes and related
      pathways among affected brain regions can provide more information on the
      mechanisms of AD. In the past decade, several studies have reported many genes
      that are associated with AD. This wealth of information has become difficult to
      follow and interpret as most of the results are conflicting. In that case, it is
      worth doing an integrated study of multiple datasets that helps to increase the
      total number of samples and the statistical power in detecting biomarkers. In
      this study, we present an integrated analysis of five different brain region
      datasets and introduce new genes that warrant further investigation. METHODS: The
      aim of our study is to apply a novel combinatorial optimisation based meta
      analysis approach to identify differentially expressed genes that are associated
      to AD across brain regions. In this study, microarray gene expression data from
      161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC),
      Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC),
      Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were
      integrated and analysed using our method. The results are then compared to two
      popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained
      by analysing the individual datasets. RESULTS: We find genes related with AD that
      are consistent with existing studies, and new candidate genes not previously
      related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along
      with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1,
      RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across
      all brain regions. Further investigation on these genes may provide new insights
      into the development of AD. In addition, we identified the presence of 23 non
      coding features, including four miRNA precursors (miR-7, miR570, miR-1229 and miR
      6821), dysregulated across the brain regions. Furthermore, we compared our
      results with two popular meta-analysis methods RankProd and GeneMeta to validate
      our findings and performed a sensitivity analysis by removing one dataset at a
      time to assess the robustness of our results. These new findings may provide new
      insights into the disease mechanisms and thus make a significant contribution in
      the near future towards understanding, prevention and cure of AD.

PMID- 27050413
TI  - Racial/Ethnic Disparities in Colorectal Cancer Screening Across Healthcare
      Systems.
AB  - INTRODUCTION: Racial/ethnic disparities in colorectal cancer (CRC) screening and
      diagnostic testing present challenges to CRC prevention programs. Thus, it is
      important to understand how differences in CRC screening approaches between
      healthcare systems are associated with racial/ethnic disparities. METHODS: This
      was a retrospective cohort study of patients aged 50-75 years who were members of
      the Population-based Research Optimizing Screening Through Personalized Regimens
      cohort from 2010 to 2012. Data on race/ethnicity, CRC screening, and diagnostic
      testing came from medical records. Data collection occurred in 2014 and analysis
      in 2015. Logistic regression models were used to calculate AORs and 95% CIs
      comparing completion of CRC screening between racial/ethnic groups. Analyses were
      stratified by healthcare system to assess differences between systems. RESULTS:
      There were 1,746,714 participants across four healthcare systems. Compared with
      non-Hispanic whites (whites), odds of completing CRC screening were lower for non
      Hispanic blacks (blacks) in healthcare systems with high screening rates
      (AOR=0.86, 95% CI=0.84, 0.88) but similar between blacks and whites in systems
      with lower screening rates (AOR=1.01, 95% CI=0.93, 1.09). Compared with whites,
      American Indian/Alaskan Natives had lower odds of completing CRC screening across
      all healthcare systems (AOR=0.76, 95% CI=0.72, 0.81). Hispanics had similar odds
      of CRC screening (AOR=0.99, 95% CI=0.98, 1.00) and Asian/Pacific Islanders had
      higher odds of CRC screening (AOR=1.16, 95% CI=1.15, 1.18) versus whites.
      CONCLUSIONS: Racial/ethnic differences in CRC screening vary across healthcare
      systems, particularly for blacks, and may be more pronounced in systems with
      intensive CRC screening approaches.

PMID- 27050414
TI  - The Spatio-temporal Distribution of Japanese Encephalitis Cases in Different Age
      Groups in Mainland China, 2004 - 2014.
AB  - BACKGROUND: Japanese encephalitis (JE) is very prevalent in China, but the
      incidence of JE among children has been greatly reduced by extensive promotion of
      vaccinations. The incidence of JE among adults, however, has increased in some
      parts of China. METHODS/PRINCIPAL FINDINGS: Data on JE in mainland China, in
      terms of incidence, gender, and age, were collected between 2004 and 2014. We
      conducted spatial and temporal analyses on data from different age groups.
      Generally, children aged 0-15 years still represent the major population of JE
      cases in China, despite the gradual decrease in incidence over years. However,
      the incidence of JE among adults in several provinces is notably higher than the
      national average, especially during the epidemic waves in 2006, 2009, and 2013.
      The JE cases in the 0-15-year-old group are distributed mainly in the area south
      of the Yangtze River, with peak incidence occurring from July to September. In
      the adult group, especially for those over 40 years old, the JE cases are
      concentrated mainly in the area north of the Yangtze River. JE incidence in the
      adult group in September and October is significantly greater compared to the
      other groups. Further analysis using Local Indicators of Spatial Association
      (LISA) reveals that the distribution of adult JE cases in the six provinces north
      of the Yangtze River, between north 30-35 degrees  latitude and east 110-130
      degrees  longitude, is a hotspot for adult JE cases. CONCLUSIONS/SIGNIFICANCE:
      The rate of JE case increase for adults is much greater than for children and has
      become a public health issue. Therefore, studies on the necessity and feasibility
      of vaccinating adults who live in JE-endemic areas, but have never been
      vaccinated for JE, should become a new focus of JE prevention in the future.

PMID- 27050416
TI  - Targeting Survivin Enhances Chemosensitivity in Retinoblastoma Cells and
      Orthotopic Tumors.
AB  - Treatments for retinoblastoma (Rb) vary depending on the size and location of the
      intraocular lesions and include chemotherapy and radiation therapy. We examined
      whether agents used to treat Rb induce a pro-survival phenotype associated with
      increased expression of survivin, a member of the inhibitor of apoptosis family
      of proteins. We document that exposure to carboplatin, topotecan or radiation
      resulted in elevated expression of survivin in two human Rb cell lines but not in
      normal retinal pigmented epithelial (RPE) cells. Cellular levels of survivin were
      attenuated in Rb cells exposed to an imidazolium-based survivin suppressant,
      Sepantronium bromide (YM155). Protein expression patterns of survivin in RPE
      cells were not altered following treatment protocols involving exposure to YM155.
      Including YM155 with chemotherapy or radiation increased levels of apoptosis in
      Rb cells but not in RPE cells. Intraocular luciferase expressing Rb tumors were
      generated from the Rb cell lines and used to evaluate the effects of carboplatin
      and YM155 on in-vivo survivin expression and tumor growth. Carboplatin induced
      expression of survivin while carboplatin combined with YM155 reduced survivin
      expression in tumor bearing eyes. The combination protocol was also most
      effective in reducing the rate of tumor regrowth. These results indicate that
      targeted inhibition of the anti-apoptotic protein survivin provides a therapeutic
      advantage for Rb cells and tumors treated with chemotherapy. 

PMID- 27050417
TI  - Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are
      Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal
      Cord Injury.
AB  - Clinical and experimental studies show that spinal cord injury (SCI) can cause
      cognitive impairment and depression that can significantly impact outcomes. Thus,
      identifying mechanisms responsible for these less well-examined, important SCI
      consequences may provide targets for more effective therapeutic intervention. To
      determine whether cognitive and depressive-like changes correlate with injury
      severity, we exposed mice to sham, mild, moderate, or severe SCI using the
      Infinite Horizon Spinal Cord Impactor and evaluated performance on a variety of
      neurobehavioral tests that are less dependent on locomotion. Cognitive impairment
      in Y-maze, novel objective recognition, and step-down fear conditioning tasks
      were increased in moderate- and severe-injury mice that also displayed depressive
      like behavior as quantified in the sucrose preference, tail suspension, and
      forced swim tests. Bromo-deoxyuridine incorporation with immunohistochemistry
      revealed that SCI led to a long-term reduction in the number of newly-generated
      immature neurons in the hippocampal dentate gyrus, accompanied by evidence of
      greater neuronal endoplasmic reticulum (ER) stress. Stereological analysis
      demonstrated that moderate/severe SCI reduced neuronal survival and increased the
      number of activated microglia chronically in the cerebral cortex and hippocampus.
      The potent microglial activator cysteine-cysteine chemokine ligand 21 (CCL21) was
      elevated in the brain sites after SCI in association with increased microglial
      activation. These findings indicate that SCI causes chronic neuroinflammation
      that contributes to neuronal loss, impaired hippocampal neurogenesis and
      increased neuronal ER stress in important brain regions associated with cognitive
      decline and physiological depression. Accumulation of CCL21 in brain may subserve
      a pathophysiological role in cognitive changes and depression after SCI.

PMID- 27050418
TI  - Measuring Hair Cortisol Concentrations to Assess the Effect of Anthropogenic
      Impacts on Wild Chimpanzees (Pan troglodytes).
AB  - Non-human primates face major environmental changes due to increased human
      impacts all over the world. Although some species are able to survive in certain
      landscapes with anthropogenic impact, their long-term viability and fitness may
      be decreased due to chronic stress. Here we assessed long-term stress levels
      through cortisol analysis in chimpanzee hair obtained from sleeping nests in
      northwestern Uganda, in order to estimate welfare in the context of ecotourism,
      forest fragmentation with human-wildlife conflicts, and illegal logging with
      hunting activity (albeit not of primates), compared with a control without human
      contact or conflict. Concerning methodological issues, season [F(2,129) = 37.4, p
      < 0.0001, r2 = 0.18] and the age of nests [F(2,178) = 20.3, p < 0.0001, r2 =
      0.11] significantly predicted hair cortisol concentrations (HCC). With regard to
      effects of anthropogenic impacts, our results neither showed elevation of HCC due
      to ecotourism, nor due to illegal logging compared to their control groups. We
      did, however, find significantly increased HCC in the fragment group compared to
      chimpanzees living in a nearby intact forest [F(1,88) = 5.0, p = 0.03, r2 =
      0.20]. In conclusion, our results suggest that hair cortisol analysis is a
      powerful tool that can help understanding the impact of anthropogenic
      disturbances on chimpanzee well-being and could be applied to other great ape
      species. 

PMID- 27050419
TI  - A quick colorimetric method for total lipid quantification in microalgae.
AB  - Discovering microalgae with high lipid productivity are among the key milestones
      for achieving sustainable biodiesel production. Current methods of lipid
      quantification are time intensive and costly. A rapid colorimetric method based
      on sulfo-phospho-vanillin (SPV) reaction was developed for the quantification of
      microbial lipids to facilitate screening for lipid producing microalgae. This
      method was successfully tested on marine thraustochytrid strains and vegetable
      oils. The colorimetric method results correlated well with gravimetric method
      estimates. The new method was less time consuming than gravimetric analysis and
      is quantitative for lipid determination, even in the presence of carbohydrates,
      proteins and glycerol.

PMID- 27050420
TI  - The contribution of pUL74 to growth of human cytomegalovirus is masked in the
      presence of RL13 and UL128 expression.
AB  - The glycoproteins gH and gL of human cytomegalovirus (HCMV) form a complex either
      with pUL74 (trimeric complex) or with proteins of the UL128 locus (pentameric
      complex). While the pentameric complex is dispensable for viral growth in
      fibroblasts, deletion of pUL74 causes a small plaque phenotype in HCMV lab
      strains, accompanied by greatly reduced cell-free infectivity. As HCMV isolates,
      shortly after cultivation from clinical specimens, do not release cell-free
      infectious viruses, we wondered whether deletion of pUL74 would also affect virus
      growth in this background. To address this question, we took advantage of the
      bacterial artificial chromosome (BAC)-cloned virus Merlin-RL13tetO, which grows
      cell associated due to the inducible expression of the viral RL13 gene, thereby
      resembling clinical isolates. Stop codons were introduced by seamless mutagenesis
      into UL74 and/or the UL128 locus to prevent expression of the trimeric or
      pentameric complex, respectively. Virus mutants were reconstituted by
      transfection of the respective genomes into cultured cells and analysed with
      respect to focal growth. When the UL128 locus was intact, deletion of pUL74 did
      not notably affect focal growth of Merlin, irrespective of RL13 expression. In
      the absence of UL128 expression, foci were increased compared with wild-type, and
      infectious cell-free virus was produced. Under these conditions, disruption of
      UL74 completely prevented virus spread from initially transfected cells to
      surrounding cells. In conclusion the contribution of pUL74 is masked when the
      UL128 locus is expressed at high levels, and its role in cell-free virus spread
      is only revealed when expression of the pentameric complex is inhibited.

PMID- 27050421
TI  - The Functional Human C-Terminome.
AB  - All translated proteins end with a carboxylic acid commonly called the C
      terminus. Many short functional sequences (minimotifs) are located on or
      immediately proximal to the C-terminus. However, information about the function
      of protein C-termini has not been consolidated into a single source. Here, we
      built a new "C-terminome" database and web system focused on human proteins.
      Approximately 3,600 C-termini in the human proteome have a minimotif with an
      established molecular function. To help evaluate the function of the remaining C
      termini in the human proteome, we inferred minimotifs identified by
      experimentation in rodent cells, predicted minimotifs based upon consensus
      sequence matches, and predicted novel highly repetitive sequences in C-termini.
      Predictions can be ranked by enrichment scores or Gene Evolutionary Rate
      Profiling (GERP) scores, a measurement of evolutionary constraint. By searching
      for new anchored sequences on the last 10 amino acids of proteins in the human
      proteome with lengths between 3-10 residues and up to 5 degenerate positions in
      the consensus sequences, we have identified new consensus sequences that predict
      instances in the majority of human genes. All of this information is consolidated
      into a database that can be accessed through a C-terminome web system with search
      and browse functions for minimotifs and human proteins. A known consensus
      sequence-based predicted function is assigned to nearly half the proteins in the
      human proteome. Weblink: http://cterminome.bio-toolkit.com. 

PMID- 27050422
TI  - Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and
      PI3K/Akt/GSK3beta Signaling Pathways in HT22 Hippocampal Neurons.
AB  - Increasing evidence shows that oxidative stress and the hyperphosphorylation of
      tau protein play essential roles in the progression of Alzheimer's disease (AD).
      Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti
      inflammatory properties. We investigated the neuroprotective effects of quercetin
      to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic
      acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396,
      Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative
      stress suppressed the cell viability and decreased the levels of lactate
      dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential
      (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA)
      production and intracellular reactive oxygen species (ROS). In addition,
      phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3beta
      (PI3K/Akt/GSK3beta) and mitogen activated protein kinase (MAPK) were also
      involved in this process. We found that pre-treatment with quercetin can
      inhibited OA-induced the hyperphosphorylation of tau protein and oxidative
      stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced
      apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but
      also via the inhibition of PI3K/Akt/GSK3beta, MAPKs and activation of NF-kappaB
      p65. Our findings suggest the therapeutic potential of quercetin to treat AD. 

PMID- 27050423
TI  - Bile Acid-Induced Suicidal Erythrocyte Death.
AB  - BACKGROUND/AIMS: In nucleated cells, bile acids may activate cation channels
      subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic
      Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes
      characterized by phosphatidylserine exposure at the cell surface and cell
      shrinkage. Eryptosis is triggered by bile duct ligation, an effect partially
      attributed to conjugated bilirubin. The present study explored, whether bile
      acids may stimulate eryptosis. METHODS: Phosphatidylserine exposing erythrocytes
      have been identified utilizing annexin V binding, cell volume estimated from
      forward scatter, cytosolic Ca2+ activity determined using Fluo-3 fluorescence,
      and ceramide abundance at the erythrocyte surface utilizing specific antibodies.
      RESULTS: The exposure of human erythrocytes to glycochenodesoxycholic (GCDC) and
      taurochenodesoxycholic (TCDC) acid was followed by a significant decrease of
      forward scatter and significant increase of Fluo-3 fluorescence, ceramide
      abundance as well as annexin V binding. The effect on annexin V binding was
      significantly blunted, but not abolished by removal of extracellular Ca2+.
      CONCLUSION: Bile acids stimulate suicidal cell death, an effect paralleled by and
      in part due to Ca2+ entry and ceramide. The bile acid induced eryptosis may in
      turn lead to accelerated clearance of circulating erythrocytes and, thus, may
      contribute to anemia in cholestatic patients.

PMID- 27050425
TI  - A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with
      Acute Myeloid Leukemia.
AB  - BACKGROUND: Although cytogenetics-based prognostication systems are well
      described in acute myeloid leukemia (AML), overall survival (OS) remains highly
      variable within risk groups. An integrated genetic prognostic (IGP) model using
      cytogenetics plus mutations in nine genes was recently proposed for patients <=60
      years to improve classification. This model has not been validated in clinical
      practice. METHODS AND FINDINGS: We retrospectively studied 197 patients with
      newly diagnosed de novo AML. We compared OS curves among the mutational profiles
      defined by the IGP model. The IGP model assigned patients with intermediate
      cytogenetics as having favorable, intermediate or unfavorable mutational
      profiles. The IGP model reassigned 50 of 137 patients with intermediate
      cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8
      years among 14 patients with intermediate cytogenetics and favorable mutational
      profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with
      intermediate mutational profiles. Among patients with intermediate cytogenetics
      labeled as having unfavorable mutational profiles, median OS was 0.8 years among
      24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8,
      TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML
      and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with
      intermediate cytogenetics and favorable mutational profiles was similar to OS for
      patients with favorable cytogenetics (p = 0.697) and different from patients with
      intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS
      among patients with FLT3-ITD positive AML and high-risk genetic changes was
      similar to patients with unfavorable cytogenetics (p = 0.793) and different from
      patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD
      negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model,
      had OS similar to patients with intermediate IGP profile (p = 0.919).
      CONCLUSIONS: The IGP model was not completely validated in our cohort. However,
      mutations in six out of the nine genes can be used to characterize survival
      (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust
      prognostication in the patients who are re-categorized by the IGP model. These
      mutations should be incorporated into clinical testing for younger patients
      outside of clinical trials, in order to guide therapy.

PMID- 27050424
TI  - Identification of Differentially Expressed microRNAs between the Fenpropathrin
      Resistant and Susceptible Strains in Tetranychus cinnabarinus.
AB  - The carmine spider mite (Tetranychus cinnabarinus) is one of the most serious
      pests on crops and its control mainly depends on chemical acaricides. The
      excessive and improper acaricides use has resulted in mite resistance to many
      acaricides, including fenpropathrin. Previous studies have indicated
      fenpropathrin resistance is a complex development process involving many genes,
      but information on resistance mechanism of post-transcription regulation is rare.
      Using Illumina sequencing, several categories of sRNAs were identified from
      susceptible (TS) and fenpropathrin-resistant strains (TR) of T. cinnabarinus,
      including 75 known microRNAs (miRNAs) and 64 novel miRNAs, whose target genes
      containing 78592 miRNA-target pairs were predicted by 6 algorithms. Also, 12
      significantly differently expressed miRNAs were identified between the TS and TR
      libraries and RT-qPCR validation also performed a well consistency with
      sequencing. The targets of significantly differentially expressed miRNAs included
      7 glutathione S-transferase, 7 cytochrome P450 and 16 carboxyl/choline esterase
      genes, their function in fenpropathrin resistance were further analyzed. The
      present study provides the firstly large-scale characterization of miRNAs in T.
      cinnabarinus and the comparison between TS and TR strains gives a clue on how
      miRNA involves in fenpropathrin resistance. 

PMID- 27050426
TI  - The Features of GGT in Patients with ATP8B1 or ABCB11 Deficiency Improve the
      Diagnostic Efficiency.
AB  - BACKGROUND AND AIMS: Genetic defects in ATP8B1 or ABCB11 account for the majority
      of cholestasis with low GGT. But the ranges for GGT in patients with ATP8B1 or
      ABCB11 deficiency are unclear. This study tried to unravel the features of GGT in
      these patients that improve diagnostic efficiency. METHODS: This study enrolled
      207 patients with chronic cholestasis who were ordered to test for ATP8B1 and/or
      ABCB11 from January 2012 to December 2015. Additional 17 patients with ATPB81 or
      ABCB11 deficiency diagnosed between January 2004 and December 2011 were also
      enrolled in this study. 600 population-matched children served as controls.
      Clinical data were obtained by retrospectively reviewing medical records.
      RESULTS: A total of 26 patients were diagnosed with ATP8B1 deficiency and 30
      patients were diagnosed with ABCB11 deficiency. GGT levels were similar between
      the two disorders at any observed month of age, but varied with age. The peak GGT
      value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and
      <50U/L beyond one year. GGT levels in patients with a genetic diagnosis were
      different from that in patients without a genetic diagnosis and controls. Larger
      ranges for GGT were found in patients without a genetic diagnosis. Some controls
      had GGT>=70U/L in the 2nd~6th month. Of the 207 patients, 39 (18.8%) obtained a
      genetic diagnosis. 111 patients met the ranges described above, including all the
      39 patients with ATP8B1 or ABCB11 deficiency. The sensitivity was 100.0%. The
      rate of a positive molecular diagnosis increased to 35.1% (39/111 vs. 39/207, X2
      = 10.363, P = 0.001). The remaining 96 patients exceeded the ranges described
      above and failed to receive a genetic diagnosis. These patients accounted for
      43.8% of sequencing cost. CONCLUSIONS: GGT levels in patients with ATP8B1 or
      ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd~6th
      month of life, <60U/L in the 7th~12th month and <50U/L beyond one year.

PMID- 27050427
TI  - Stem cell-derived cell-sheets for connective tissue engineering.
AB  - Cell-sheet technology involves the recovery of cells with its secreted ECM and
      cell-cell junctions intact, and thereby harvesting them in a single contiguous
      layer. Temperature changes coupled with a thermoresponsive polymer grafted
      culture plate surface are typically used to induce detachment of this cell-matrix
      layer by controlling the hydrophobicity and hydrophilicity properties of the
      culture surface. This review article details the genesis and development of this
      technique as a critical tissue-engineering tool, with a comprehensive discussion
      on connective tissue applications. This includes applications in the myocardial,
      vascular, cartilage, bone, tendon/ligament, and periodontal areas among others
      discussed. In particular, further focus will be given to the use of stem cells
      derived cell-sheets, such as those involving bone marrow-derived and adipose
      tissue-derived mesenchymal stem cells. In addition, some of the associated
      challenges faced by approaches using stem cells-derived cell-sheets will also be
      discussed. Finally, recent advances pertaining to technologies forming,
      detaching, and manipulating cell-sheets will be covered in view of the potential
      impact they will have on shaping the way cell-sheet technology will be utilized
      in the future as a tissue-engineering technique.

PMID- 27050428
TI  - The time course of attentional bias to cues of threat and safety.
AB  - It is well known that relative to neutral stimuli, attention is biased towards
      processing stimuli that convey threat. In a previous study in which a particular
      stimulus (e.g. a blue diamond) was associated with the delivery of an electrical
      shock, the presence of the fear-conditioned stimulus interfered with the
      execution of voluntary eye movements to other locations. Here, we show that this
      effect not only occurs early in time, but remains present long after the fear
      conditioned stimulus was removed from the screen. In a subsequent experiment, we
      associated the presence of a particular stimulus with safety, that is, when this
      stimulus was present it was certain that no electrical shock would be delivered.
      The presence of the safety signalling stimulus also interfered with the execution
      of voluntary saccades, but only when the time between stimulus and cue
      presentation was relatively long. The results indicate that both signals of
      threat and signals of safety interfere with execution of a saccade long after the
      source of threat or safety has been removed. However, only threatening stimuli
      affect saccade execution early in time, suggesting that threatening stimuli drive
      selection exogenously.

PMID- 27050429
TI  - Regulation of Coronary Endothelial Function by Interactions between TNF-alpha,
      LOX-1 and Adiponectin in Apolipoprotein E Knockout Mice.
AB  - BACKGROUND/AIMS: Although individual contributions of TNF-alpha, LOX-1 and
      adiponectin to the regulation of endothelial function were previously studied,
      their interactions in the regulation of coronary endothelial function remain
      unclear. The aim of this study is to investigate the interactions between TNF
      alpha, LOX-1 and adiponectin in endothelial dysfunction in atherosclerosis.
      METHODS: Vasodilator function was assessed in coronary arterioles isolated from
      wild-type, apolipoprotein (ApoE) knockout (KO) mice, ApoE KO null for TNF-alpha
      (ApoE KOTNF-/TNF-) and ApoE KO mice treated with neutralizing antibodies to
      either TNF-alpha and LOX-1, or recombinant adiponectin. Western blot analysis and
      immunofluorescence staining were used for mechanistic studies. RESULTS:
      Acetylcholine (Ach) dilation was impaired in ApoE KO mice. KO of TNF-alpha, anti
      TNF-alpha anti-LOX-1 or adiponectin restored impaired ACh vasodilation without
      affecting endothelium-derived hyperpolarizing factor-mediated vasodilation.
      Immunofluorescence staining demonstrated colocalization of TNF-alpha with
      vascular smooth muscle cells, and adiponectin with endothelial cells. ApoE KO
      mice showed increased protein expression of LOX-1, NF-x03BA;B, NADPH oxidase
      subunit NOX4 and nitrotyrosine (N-Tyr) levels in coronary arterioles. Treatment
      with anti-TNF-alpha, anti-LOX-1 and adiponectin suppressed protein expression of
      LOX-1, NOX4, NF-x03BA;B and N-Tyr levels. CONCLUSION: Adiponectin, anti-TNF-alpha
      and anti-LOX-1 exert vasoprotective effects in atherosclerotic ApoE KO mice.

PMID- 27050430
TI  - Seasonal Variability in Calorimetric Energy Content of Two Caribbean Mesophotic
      Corals.
AB  - Energetic responses of zooxanthellate reef corals along depth gradients have
      relevance to the refugia potential of mesophotic coral ecosystems (MCEs).
      Previous observations suggested that MCEs in the Caribbean are thermally buffered
      during the warmest parts of the year and occur within or just below the
      chlorophyll maximum, suggesting abundant trophic resources. However, it is not
      known if mesophotic corals can maintain constant energy needs throughout the year
      with changing environmental and biological conditions. The energetic content of
      tissues from the stony coral species Orbicella faveolata and Agaricia lamarcki
      was measured on the southern insular shelf of St. Thomas, US Virgin Islands
      (USVI), using micro-bomb calorimetry. Three sites for each species, at depths of
      6m, 25m, 38m and 63m, were selected to capture energetic differences across the
      major vertical range extent of both species in the USVI-and sampled over five
      periods from April 2013 to April 2014. Mesophotic colonies of O. faveolata
      exhibited a significant reduction in energetic content during the month of
      September 2013 compared to mid-depth and shallow colonies (p = 0.032), whereas A.
      lamarcki experienced similar energetic variability, but with a significant
      reduction in energy content that occurred in July 2013 for colonies at sites
      deeper than 25m (p = 0.014). The results of calorimetric analyses indicate that
      O. faveolata may be at risk during late summer stress events, possibly due to the
      timing of reproductive activities. The low-point of A. lamarcki energy content,
      which may also coincide with reproduction, occurs prior to seasonal stress
      events, indicating contrasting, species-specific responses to environmental
      variability on MCEs. 

PMID- 27050432
TI  - Crowdsourcing a Collective Sense of Place.
AB  - Place can be generally defined as a location that has been assigned meaning
      through human experience, and as such it is of multidisciplinary scientific
      interest. Up to this point place has been studied primarily within the context of
      social sciences as a theoretical construct. The availability of large amounts of
      user-generated content, e.g. in the form of social media feeds or Wikipedia
      contributions, allows us for the first time to computationally analyze and
      quantify the shared meaning of place. By aggregating references to human
      activities within urban spaces we can observe the emergence of unique themes that
      characterize different locations, thus identifying places through their
      discernible sociocultural signatures. In this paper we present results from a
      novel quantitative approach to derive such sociocultural signatures from Twitter
      contributions and also from corresponding Wikipedia entries. By contrasting the
      two we show how particular thematic characteristics of places (referred to herein
      as platial themes) are emerging from such crowd-contributed content, allowing us
      to observe the meaning that the general public, either individually or
      collectively, is assigning to specific locations. Our approach leverages
      probabilistic topic modelling, semantic association, and spatial clustering to
      find locations are conveying a collective sense of place. Deriving and
      quantifying such meaning allows us to observe how people transform a location to
      a place and shape its characteristics. 

PMID- 27050431
TI  - Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded
      Clinical Trial in Surgical Patients.
AB  - BACKGROUND: Neuropathic pain following surgical treatment for breast cancer with
      or without chemotherapy is a clinical burden and patients frequently report
      cognitive, emotional and quality of life impairment. A preclinical study recently
      showed that memantine administered before surgery may prevent neuropathic pain
      development and cognitive dysfunction. With a translational approach, a clinical
      trial has been carried out to evaluate whether memantine administered before and
      after mastectomy could prevent the development of neuropathic pain, the
      impairment of cognition and quality of life. METHOD: A randomized, pilot clinical
      trial included 40 women undergoing mastectomy in the Oncology Department,
      University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20)
      or placebo (n = 20) was administered for four weeks starting two weeks before
      surgery. The primary endpoint was pain intensity measured on a (0-10) numerical
      rating scale at three months post-mastectomy. RESULTS: Data analyses were
      performed using mixed models and the tests were two-sided, with a type I error
      set at alpha = 0.05. Compared with placebo, patients receiving memantine showed
      at three months a significant difference in post-mastectomy pain intensity, less
      rescue analgesia and a better emotional state. An improvement of pain symptoms
      induced by cancer chemotherapy was also reported. CONCLUSIONS: This study shows
      for the first time the beneficial effect of memantine to prevent post-mastectomy
      pain development and to diminish chemotherapy-induced pain symptoms. The lesser
      analgesic consumption and better well-being of patients for at least six months
      after treatment suggests that memantine could be an interesting therapeutic
      option to diminish the burden of breast cancer therapy. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01536314.

PMID- 27050433
TI  - Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of
      Atherosclerosis.
AB  - A population-based cohort showed an association between cigarette smoking and
      subclinical parenchymal lung disease defined as regions of increased computed
      tomography (CT) lung densitometry. This technique has not been applied to the
      rheumatoid arthritis (RA) population where associated ILD is highly prevalent.
      The association between cumulative cigarette smoking and volume of areas of high
      attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was
      compared in 172 RA participants and 3,969 controls in a general population
      sample. Multivariable regression models were used to adjust for demography,
      anthropometrics, percent emphysema, and CT parameters. The mean cumulative
      cigarette smoking exposure was 25 (IQR 10-42) and 15(IQR 5-31) pack-years for the
      RA and non-RA cohorts, respectively. Mean HAA was 153(+/-57) cm3 and 129(+/-50)
      cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year
      increment was associated with a higher HAA by 0.03% (95% CI, 0.007-0.05%) in RA
      patients and by 0.008% (95% CI, 0.003-0.01%) in those without RA (interaction p =
      0.001). Cigarette smoking was associated with higher lung attenuation; with a
      magnitude of association more pronounced in those with RA than in the general
      population. These data suggest that cigarette smoking may be a more potent ILD
      risk factor for RA patients than in the general population. 

PMID- 27050434
TI  - C/EBPalpha Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma
      through Inhibiting EGFR/beta-Catenin Signaling Mediated EMT.
AB  - Hepatocellular carcinoma is associated with high mortality, and tumor metastasis
      is an important reason for poor prognosis. However, metastasis has not been
      effectively prevented in clinical therapy and the mechanisms underlying
      metastasis have not been fully characterized. CCAAT/enhancer-binding protein
      alpha (C/EBPalpha) is a transcriptional regulator with an essential role in tumor
      metastasis. We used short-activating RNAs (saRNA) to enhance expression of
      C/EBPalpha. Intravenous injection of C/EBPalpha-saRNA in a nude mouse liver
      orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis.
      C/EBPalpha-saRNA-treated mice showed increased serum levels of albumin and
      decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST),
      indicating a role of C/EBPalpha in improving liver function. Migration and
      invasion were inhibited in hepatoma cell lines transfected with C/EBPalpha-saRNA.
      We also observed an inhibition of epithelial-mesenchymal transition (EMT) and
      suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and
      beta-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that
      C/EBPalpha-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/beta
      catenin signaling pathway mediated EMT in vitro and in vivo. 

PMID- 27050435
TI  - Distribution and Function of PACAP and Its Receptors in the Healthy and Nephrotic
      Kidney.
AB  - BACKGROUND/AIMS: Plasma deficiency of pituitary adenylate cyclase-activating
      polypeptide (PACAP) was recently demonstrated in children with nephrotic syndrome
      (NS). Previous studies have reported an important protective effect of PACAP on
      kidney proximal tubules. The aim of this study was to explore the expression of
      PACAP and its receptors PAC1, VPAC1 and VPAC2 in the healthy and nephrotic kidney
      and to determine if PACAP has an effect on renal proximal tubular cells exposed
      to albumin. METHODS: Expression of PACAP and its receptors was studied using
      kidney tissue from healthy and nephrotic children, and in 3 human renal cell
      lines (glomerular microvascular endothelial cells, podocytes and proximal tubular
      epithelial HK-2 cells). The functionality of the VPAC1 receptor was tested in HK
      2 cells, measuring cyclic adenosine monophosphate levels after PACAP exposure.
      The influence of PACAP on cell viability and transforming growth factor-beta1
      (TGF-beta1) expression was measured in HK-2 cells exposed to albumin, mimicking
      proteinuria related damage. RESULTS: VPAC1 expression was detected in the tubular
      proximal epithelial cells and in the glomerular podocytes of renal tissue from
      healthy and nephrotic children. Increased staining for PACAP was found in the
      proximal tubules of renal sections from children with NS compared to healthy
      renal sections. Expression and functionality of VPAC1 were demonstrated in HK-2
      cells. Finally, PACAP did not alter cell viability or TGF-beta1 expression of HK
      2 cells exposed to albumin. CONCLUSION: VPAC1 is the predominant receptor in the
      human kidney. The enhanced presence of PACAP in proximal tubular epithelial cells
      in nephrotic kidneys points to the reabsorption of filtered PACAP. On short term,
      PACAP has no in vitro effect on cell viability and TGF-beta1 expression of
      proximal tubular epithelial cells exposed to high concentrations of albumin.

PMID- 27050436
TI  - Polymyositis following autologous haematopoietic stem cell transplantation.

PMID- 27050438
TI  - Impact of bariatric surgery in obstructive sleep apnea in obese patients.

PMID- 27050437
TI  - Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia.
AB  - BACKGROUND: We hypothesized that obstructive sleep apnea (OSA) can predispose
      individuals to lower airway infections and community-acquired pneumonia (CAP) due
      to upper airway microaspiration. This study evaluated the association between OSA
      and CAP. METHODS: We performed a case-control study that included 82 patients
      with CAP and 41 patients with other infections (control group). The controls were
      matched according to age, sex and body mass index (BMI). A respiratory polygraph
      (RP) was performed upon admission for patients in both groups. The severity of
      pneumonia was assessed according to the Pneumonia Severity Index (PSI). The
      associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA
      severity and other sleep-related variables were evaluated using logistic
      regression models. The associations between OSA, OSA severity with CAP severity
      were evaluated with linear regression models and non-parametric tests. FINDINGS:
      No significant differences were found between CAP and control patients regarding
      anthropometric variables, toxic habits and risk factors for CAP. Patients with
      OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) >=10, showed an
      increased risk of CAP (OR = 2.86, 95%CI 1.29-6.44, p = 0.01). Patients with
      severe OSA (AHI>=30) also had a higher risk of CAP (OR = 3.18, 95%CI 1.11-11.56,
      p = 0.047). In addition, OSA severity, defined according to the AHI quartile, was
      also significantly associated with CAP (p = 0.007). Furthermore, OSA was
      significantly associated with CAP severity (p = 0.0002), and OSA severity was
      also associated with CAP severity (p = 0.0006). CONCLUSIONS: OSA and OSA severity
      are associated with CAP when compared to patients admitted to the hospital for
      non-respiratory infections. In addition, OSA and OSA severity are associated with
      CAP severity. These results support the potential role of OSA in the pathogenesis
      of CAP and could have clinical implications. This link between OSA and infection
      risk should be explored to investigate the relationships among gastroesophageal
      reflux, silent aspiration, laryngeal sensory dysfunction and CAP. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01071421.

PMID- 27050439
TI  - The development and evaluation of mini-GEMs - short, focused, online e-learning
      videos in geriatric medicine.
AB  - Mini Geriatric E-Learning Modules (Mini-GEMs) are short, focused, e-learning
      videos on geriatric medicine topics, hosted on YouTube, which are targeted at
      junior doctors working with older people. This study aimed to explore how these
      resources are accessed and used. The authors analyzed the viewing data from 22
      videos published over the first 18 months of the Mini-GEM project. We conducted a
      focus group of U.K. junior doctors considering their experiences with Mini-GEMS.
      The Mini-GEMs were viewed 10,291 times over 18 months, equating to 38,435 minutes
      of total viewing time. The average viewing time for each video was 3.85 minutes.
      Learners valued the brevity and focused nature of the Mini-GEMs and reported that
      they watched them in a variety of settings to supplement clinical experiences and
      consolidate learning. Watching the videos led to an increase in self-reported
      confidence in managing older patients. Mini-GEMs can effectively disseminate
      clinical teaching material to a wide audience. The videos are valued by junior
      doctors due to their accessibility and ease of use.

PMID- 27050440
TI  - Outlier Loci Detect Intraspecific Biodiversity amongst Spring and Autumn Spawning
      Herring across Local Scales.
AB  - Herring, Clupea harengus, is one of the ecologically and commercially most
      important species in European northern seas, where two distinct ecotypes have
      been described based on spawning time; spring and autumn. To date, it is unknown
      if these spring and autumn spawning herring constitute genetically distinct
      units. We assessed levels of genetic divergence between spring and autumn
      spawning herring in the Baltic Sea using two types of DNA markers,
      microsatellites and Single Nucleotide Polymorphisms, and compared the results
      with data for autumn spawning North Sea herring. Temporally replicated analyses
      reveal clear genetic differences between ecotypes and hence support reproductive
      isolation. Loci showing non-neutral behaviour, so-called outlier loci, show
      convergence between autumn spawning herring from demographically disjoint
      populations, potentially reflecting selective processes associated with autumn
      spawning ecotypes. The abundance and exploitation of the two ecotypes have varied
      strongly over space and time in the Baltic Sea, where autumn spawners have faced
      strong depression for decades. The results therefore have practical implications
      by highlighting the need for specific management of these co-occurring ecotypes
      to meet requirements for sustainable exploitation and ensure optimal livelihood
      for coastal communities.

PMID- 27050441
TI  - Trehalose effectiveness as a cryoprotectant in 2D and 3D cell cultures of human
      embryonic kidney cells.
AB  - Post cryopreservation viability of human embryonic kidney (HEK) cells under two
      dimensional (2D) and three-dimensional (3D) culture conditions was studied using
      trehalose as the sole cryoprotective agent. An L9 (34) Taguchi design was used to
      optimize the cryoprotection cocktail seeding process prior to slow-freezing with
      the specific aim of maximizing cell viability measured 7 days post thaw, using
      the combinatorial cell viability and in-vitro cytotoxicity WST assay. At low (200
      mM) and medium (800 mM) levels of trehalose concentration, encapsulation in
      alginate offered a greater protection to cryopreservation. However, at the
      highest trehalose concentration (1200 mM) and in the absence of the pre
      incubation step, there was no statistical difference at the 95% CI (p = 0.0212)
      between the viability of the HEK cells under 2D and 3D culture conditions
      estimated to be 17.9 +/- 4.6% and 14.0 +/- 3.6%, respectively. A parallel
      comparison between cryoprotective agents conducted at the optimal levels of the
      L9 study, using trehalose, dimethylsulfoxide and glycerol in alginate
      microcapsules yielded a viability of 36.0 +/- 7.4% for trehalose, in average 75%
      higher than the results associated with the other two cell membrane-permeating
      compounds. In summary, the effectiveness of trehalose has been demonstrated by
      the fact that 3D cell cultures can readily be equilibrated with trehalose before
      cryopreservation, thus mitigating the cytotoxic effects of glycerol and
      dimethylsulfoxide.

PMID- 27050442
TI  - Cerebellar involvement in essential tremor with and without resting tremor: A
      Diffusion Tensor Imaging study.
AB  - OBJECTIVE: Essential Tremor with resting tremor (rET) is a debated and poorly
      understood clinical phenotype. Converging evidences show that neurodegeneration
      of the cerebellum underlies the pathophysiology of ET, but it is not known if
      cerebellar changes also occurs in patients with rET. The aim of our study was to
      evaluate cerebellar microstructure in patients with ET with- (rET) and without
      resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor
      Imaging (DTI). METHODS: We studied 67 patients with ET (rET: 29 and ETwr: 38) and
      39 age-matched healthy controls (HC). DTI was performed to measure fractional
      anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in
      the entire cerebellum and in right and left cerebellar hemispheres. RESULTS: MD
      was significantly higher in the cerebellar GM of ET total group (10.39 +/- 0.87)
      in comparison with HC (9.90 +/- 0.71) (p = 0.0027). Interestingly, MD was
      significantly different when ETwr (10.48 +/- 0.77) were compared with HC (p =
      0.0017), whereas a trend toward significance were found between rET (10.29 +/-
      0.99) and HC (p = 0.067). No differences among groups were found in MD of
      cerebellar WM and in FA values neither in the WM nor in the GM. CONCLUSION: Our
      results demonstrate the presence of microstructural changes in the cerebellum of
      patients with ET. It is noteworthy that rET showed intermediate values compared
      to HC and ETwr, suggesting that rET shares part of the pathophysiological
      mechanisms of ETwr, but cerebellar involvement seems do not fully account for
      rET. In addition to the cerebellar loops, other networks may play a role in rET
      pathophysiology.

PMID- 27050443
TI  - Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after
      Myocardial Infarction: Are Animal Models Robust Enough?
AB  - BACKGROUND: Human mesenchymal stromal cells (MSCs) have been reported to preserve
      cardiac function in myocardial infarction (MI) models. Previously, we found a
      beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs)
      on cardiac function after permanent coronary artery ligation. In the present
      study we aimed to extend this research by investigating the effect of
      intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory
      cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown
      additional salutary effects in multiple experimental disease models. METHODS: MI
      was induced in NOD/Scid mice by permanent ligation of the left anterior
      descending coronary artery. Animals received intramyocardial injection of uMSCs,
      iMSCs or PBS. Sham-operated animals were used to determine baseline
      characteristics. Cardiac performance was assessed after 2 and 14 days using 7
      Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology
      and q-PCR were used to confirm MSC engraftment in the heart. RESULTS: Both uMSC
      and iMSC therapy had no significant beneficial effect on cardiac function or
      remodelling in contrast to our previous studies. CONCLUSIONS: Animal models for
      cardiac MSC therapy appear less robust than initially envisioned.

PMID- 27050444
TI  - Enhanced Exciton Binding Energy of ZnO by Long-Distance Perturbation of Doped Be
      Atoms.
AB  - The excitonic effect in semiconductors is sensitive to dopants. Origins of dopant
      induced large variation in the exciton binding energy (E(b)) is not well
      understood and has never been systematically studied. We choose ZnO as a typical
      high-E(b) material, which is very promising in low-threshold lasing. To the best
      of our knowledge, its shortest wavelength electroluminescence lasing was realized
      by ZnO/BeZnO multiple quantum wells (MQWs). However, this exciting result is
      shadowed by a controversial E(b) enhancement claimed. In this Letter, we reveal
      that the claimed E(b) is sensible if we take Be-induced E(b) variation into
      account. Detailed first-principle investigation of the interaction between dopant
      atoms and the lattice shows that the enhancement mainly comes from the long
      distance perturbation of doped Be atoms rather than the local effect of doping
      atoms. This is a joint work of experiment and calculation, which from the angle
      of methology paves the way for understanding and predicting the E(b) variation
      induced by doping.

PMID- 27050445
TI  - Practice Variation Among Hospitals in Revascularization Therapy and Its
      Association With Procedure-related Mortality.
AB  - BACKGROUND: While substantial practice variation in coronary revascularization
      has been described and deviation from clinical practice guidelines has been
      associated with worse outcomes, the degree to which this is driven by flawed
      decision making and/or appropriate deviation associated with comorbid conditions
      is unknown. We evaluated heterogeneity in procedure use, and the extent to which
      hospital-level practice variation is related to surgical mortality. METHODS: We
      analyzed data on 554,563 inpatients undergoing either percutaneous coronary
      intervention or coronary artery bypass grafting at 391 centers in 6 states.
      Procedure-specific risk models were developed based on demographics and
      comorbidities, allowing for differential effects of comorbidities for each sex.
      For each patient, the revascularization procedure that minimized predicted
      probability of inhospital mortality was designated as the model-preferred
      procedure.Hospital-level discordance rates-the proportion of cases in each
      hospital for which the opposite from the model-preferred procedure was performed
      were calculated. Hierarchical linear models were used to analyze the relationship
      between HDRs and hospital-level risk-standardized mortality ratios (RSMRs).
      RESULTS: Comorbidities and demographics alone explained between 68% and 86% of
      overall variation in inhospital mortality (corresponding C-statistics of 0.84
      0.93). The mean (SD) HDR was 26.3% (9.6%). There was a positive independent
      association between HDRs and inhospital mortality, with a 10% increase in HDR
      associated with an 11% increase in RSMR (P<0.001). CONCLUSIONS: Variance in
      procedure use according to model preference was strongly associated with worse
      outcomes. A systematic approach to incorporating comorbidity as part of the
      decision-making process for coronary revascularization is needed.

PMID- 27050446
TI  - What Works in Readmissions Reduction: How Hospitals Improve Performance.
AB  - BACKGROUND: Hospitals across the United States are pursuing strategies to reduce
      avoidable readmissions but the evidence on how best to accomplish this goal is
      mixed, with no specific clinical practice shown to reduce readmissions
      consistently. Changes to hospital organizational practices, a key component of
      context, also may be critical to improving performance on readmissions, but this
      has not been studied. OBJECTIVE: The aim of this study was to understand how high
      performing hospitals improved risk-stratified readmission rates, and whether
      their changes to clinical practices and organizational practices differed from
      low-performing hospitals. DESIGN: This was a qualitative study of 10 hospitals in
      which readmission rates had decreased (n=7) or increased (n=3). PARTICIPANTS: A
      total of 82 hospital staff drawn from hospitals that had participated in the
      State Action on Avoidable Readmissions quality improvement initiative. RESULTS:
      High-performing hospitals were distinguished by several organizational practices
      that facilitated readmissions reduction, that is, collective habits of action or
      interpretation shared by organization members. First, high-performing hospitals
      reported focused efforts to improve collaboration across hospital departments.
      Second, they helped postacute providers improve care by sharing the hospital's
      clinical and quality improvement expertise and data. Third, high performers
      enthusiastically engaged in trial and error learning to reduce readmissions.
      Fourth, they emphasized that readmissions represented bad outcomes for patients,
      de-emphasizing the role of financial penalties. Both high-performing and low
      performing hospitals had implemented most clinical practice changes commonly
      recommended to reduce readmissions. CONCLUSIONS: Our findings highlight several
      organizational practices that hospitals may be able to use to enhance the
      effectiveness of their readmissions reduction efforts.

PMID- 27050448
TI  - [Pulmonary (Arterial) Hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a rare disease characterised by vascular
      remodelling of the small lung arteries leading to a decrease of the vessel lumen
      and eventually to occlusion. According to the current guidelines, PAH is defined
      by a pulmonary arterial pressure >= 25 mmHg, an arterial wedge pressure <= 15
      mmHg, and an elevated pulmonary vascular resistance (PVR > 3 WU). The current
      pathophysiological concepts include disturbances in the production, deposition
      and composition of the extracellular matrix, inflammatory processes, mutations in
      the BMPR2 gene as well as mutations in the KCNK3 gene. During the last few years,
      epigenetic and genetic investigations resulted in new findings which are highly
      relevant for the diagnosis, prognosis and therapy of PAH. These findings could
      lead to the development of new, individualised therapy strategies. Currently,
      several phase I and phase II studies are in progress, in which promising new
      substances are examined.

PMID- 27050447
TI  - Community Attitudes and Practices of Urban Residents Regarding Predation by Pet
      Cats on Wildlife: An International Comparison.
AB  - International differences in practices and attitudes regarding pet cats'
      interactions with wildlife were assessed by surveying citizens from at least two
      cities in Australia, New Zealand, the UK, the USA, China and Japan. Predictions
      tested were: (i) cat owners would agree less than non-cat owners that cats might
      threaten wildlife, (ii) cat owners value wildlife less than non-cat owners, (iii)
      cat owners are less accepting of cat legislation/restrictions than non-owners,
      and (iv) respondents from regions with high endemic biodiversity (Australia, New
      Zealand, China and the USA state of Hawaii) would be most concerned about pet
      cats threatening wildlife. Everywhere non-owners were more likely than owners to
      agree that pet cats killing wildlife were a problem in cities, towns and rural
      areas. Agreement amongst non-owners was highest in Australia (95%) and New
      Zealand (78%) and lowest in the UK (38%). Irrespective of ownership, over 85% of
      respondents from all countries except China (65%) valued wildlife in cities,
      towns and rural areas. Non-owners advocated cat legislation more strongly than
      owners except in Japan. Australian non-owners were the most supportive (88%),
      followed by Chinese non-owners (80%) and Japanese owners (79.5%). The UK was
      least supportive (non-owners 43%, owners 25%). Many Australian (62%), New Zealand
      (51%) and Chinese owners (42%) agreed that pet cats killing wildlife in cities,
      towns and rural areas was a problem, while Hawaiian owners were similar to the
      mainland USA (20%). Thus high endemic biodiversity might contribute to attitudes
      in some, but not all, countries. Husbandry practices varied internationally, with
      predation highest where fewer cats were confined. Although the risk of wildlife
      population declines caused by pet cats justifies precautionary action, campaigns
      based on wildlife protection are unlikely to succeed outside Australia or New
      Zealand. Restrictions on roaming protect wildlife and benefit cat welfare, so
      welfare is a better rationale. 

PMID- 27050449
TI  - Ways of Doing: Restorative Practices, Governmentality, and Provider Conduct in
      Post-Apartheid Health Care.
AB  - In this article, we consider the conduct of post-apartheid health care in a
      policy context directed toward entrenching democracy, ensuring treatment-adherent
      patients, and creating a healthy populace actively responsible for their own
      health. We ask how tuberculosis treatment, antiretroviral therapy, and maternal
      services are delivered within South Africa's health system, an institutional site
      of colonial and apartheid injustice, and democratic reform. Using Foucauldian and
      post-Foucauldian notions of governmentality, we explore provider ways of doing
      to, for, and with patients in three health subdistricts. Although restorative
      provider engagements are expected in policy, older authoritarian and
      paternalistic norms persist in practice. These challenge and reshape, even 'undo'
      democratic assertions of citizenship, while producing compliant, self-responsible
      patients. Alongside the need to address pervasive structural barriers to health
      care, a restorative approach requires community participation, provider
      accountability, and a health system that does with providers as much as providers
      who do with patients.

PMID- 27050451
TI  - Recent advances in inorganic materials for LDI-MS analysis of small molecules.
AB  - In this review, various inorganic materials were summarized for the analysis of
      small molecules by laser desorption/ionization mass spectrometry (LDI-MS). Due to
      its tremendous advantages, such as simplicity, high speed, high throughput, small
      analyte volumes and tolerance towards salts, LDI-MS has been widely used in
      various analytes. During the ionization process, a suitable agent is required to
      assist the ionization, such as an appropriate matrix for matrix assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). However, it is normally
      difficult to analyze small molecules with the MALDI technique because
      conventional organic matrices may produce matrix-related peaks in the low
      molecular-weight region, which limits the detection of small molecules (m/z < 700
      Da). Therefore, more and more inorganic materials, including carbon-based
      materials, silicon-based materials and metal-based materials, have been developed
      to assist the ionization of small molecules. These inorganic materials can
      transfer energy and improve the ionization efficiency of analytes. In addition,
      functionalized inorganic materials can act as both an adsorbent and an agent in
      the enrichment and ionization of small molecules. In this review, we mainly focus
      on present advances in inorganic materials for the LDI-MS analysis of small
      molecules in the last five years, which contains the synthetic protocols of novel
      inorganic materials and the detailed results achieved by inorganic materials. On
      the other hand, this review also summarizes the application of inorganic
      materials as adsorbents in the selective enrichment of small molecules, which
      provides a new field for the application of inorganic materials.

PMID- 27050450
TI  - Reduced Prefrontal Cortex Hemodynamic Response in Adults with Methamphetamine
      Induced Psychosis: Relevance for Impulsivity.
AB  - Patients with methamphetamine abuse/dependence often exhibit high levels of
      impulsivity, which may be associated with the structural abnormalities and
      functional hypoactivities observed in the frontal cortex of these subjects.
      Although near-infrared spectroscopy (NIRS) is a simple and non-invasive method
      for characterizing the clinical features of various psychiatric illnesses, few
      studies have used NIRS to directly investigate the association between prefrontal
      cortical activity and inhibitory control in patients with methamphetamine-induced
      psychosis (MAP). Using a 24-channel NIRS system, we compared hemodynamic
      responses during the Stroop color-word task in 14 patients with MAP and 21
      healthy controls matched for age, sex and premorbid IQ. In addition, we used the
      Barrett Impulsivity Scale-11 (BIS-11) to assess impulsivity between subject
      groups. The MAP group exhibited significantly less activation in the anterior and
      frontopolar prefrontal cortex accompanied by lower Stroop color-word task
      performance, compared with controls. Moreover, BIS-11 scores were significantly
      higher in the MAP group, and were negatively correlated with the hemodynamic
      responses in prefrontal cortex. Our data suggest that reduced hemodynamic
      responses in the prefrontal cortex might reflect higher levels of impulsivity in
      patients with MAP, providing new insights into disrupted inhibitory control
      observed in MAP. 

PMID- 27050452
TI  - Autophagy is a key factor in maintaining the regenerative capacity of muscle stem
      cells by promoting quiescence and preventing senescence.
AB  - Autophagy, a highly regulated cellular degradation and recycling process, can
      occur constitutively at a basal level, and plays an essential role in many
      aspects of cell physiology. A recently published study (see the related punctum
      in Autophagy, Vol. 12, No. 4) suggests that basal autophagy is also important for
      maintaining the regenerative capacity of muscle stem cells, and that the decline
      of autophagy with aging is the cause of entry into senescence from quiescence in
      satellite cells. 

PMID- 27050453
TI  - A lysosome-centered view of nutrient homeostasis.
AB  - Lysosomes are highly acidic cellular organelles traditionally viewed as sacs of
      enzymes involved in digesting extracellular or intracellular macromolecules for
      the regeneration of basic building blocks, cellular housekeeping, or pathogen
      degradation. Bound by a single lipid bilayer, lysosomes receive their substrates
      by fusing with endosomes or autophagosomes, or through specialized translocation
      mechanisms such as chaperone-mediated autophagy or microautophagy. Lysosomes
      degrade their substrates using up to 60 different soluble hydrolases and release
      their products either to the cytosol through poorly defined exporting and efflux
      mechanisms or to the extracellular space by fusing with the plasma membrane.
      However, it is becoming evident that the role of the lysosome in nutrient
      homeostasis goes beyond the disposal of waste or the recycling of building
      blocks. The lysosome is emerging as a signaling hub that can integrate and relay
      external and internal nutritional information to promote cellular and organismal
      homeostasis, as well as a major contributor to the processing of energy-dense
      molecules like glycogen and triglycerides. Here we describe the current knowledge
      of the nutrient signaling pathways governing lysosomal function, the role of the
      lysosome in nutrient mobilization, and how lysosomes signal other organelles,
      distant tissues, and even themselves to ensure energy homeostasis in spite of
      fluctuations in energy intake. At the same time, we highlight the value of
      genomics approaches to the past and future discoveries of how the lysosome
      simultaneously executes and controls cellular homeostasis. 

PMID- 27050454
TI  - Cytosolic PINK1 promotes the targeting of ubiquitinated proteins to the aggresome
      autophagy pathway during proteasomal stress.
AB  - During proteasomal stress, cells can alleviate the accumulation of
      polyubiquitinated proteins by targeting them to perinuclear aggresomes for
      autophagic degradation, but the mechanism underlying the activation of this
      compensatory pathway remains unclear. Here we report that PINK1-s, a short form
      of Parkinson disease (PD)-related protein kinase PINK1 (PTEN induced putative
      kinase 1), is a major regulator of aggresome formation. PINK1-s is extremely
      unstable due to its recognition by the N-end rule pathway, and tends to
      accumulate in the cytosol during proteasomal stress. Overexpression of PINK1-s
      induces aggresome formation in cells with normal proteasomal activities, while
      loss of PINK1-s function leads to a significant decrease in the efficiency of
      aggresome formation induced by proteasomal inhibition. PINK1-s exerts its effect
      through phosphorylation of the ubiquitin-binding protein SQSTM1 (sequestosome 1)
      and increasing its ability to sequester polyubiquitinated proteins into
      aggresomes. These findings pinpoint PINK1-s as a sensor of proteasomal activities
      that transduces the proteasomal impairment signal to the aggresome formation
      machinery. 

PMID- 27050455
TI  - Phosphorylation of Atg9 regulates movement to the phagophore assembly site and
      the rate of autophagosome formation.
AB  - Macroautophagy is primarily a degradative process that cells use to break down
      their own components to recycle macromolecules and provide energy under stress
      conditions, and defects in macroautophagy lead to a wide range of diseases. Atg9,
      conserved from yeast to mammals, is the only identified transmembrane protein in
      the yeast core macroautophagy machinery required for formation of the
      sequestering compartment termed the autophagosome. This protein undergoes dynamic
      movement between the phagophore assembly site (PAS), where the autophagosome
      precursor is nucleated, and peripheral sites that may provide donor membrane for
      expansion of the phagophore. Atg9 is a phosphoprotein that is regulated by the
      Atg1 kinase. We used stable isotope labeling by amino acids in cell culture
      (SILAC) to identify phosphorylation sites on this protein and identified an Atg1
      independent phosphorylation site at serine 122. A nonphosphorylatable Atg9 mutant
      showed decreased autophagy activity, whereas the phosphomimetic mutant enhanced
      activity. Electron microscopy analysis suggests that the different levels of
      autophagy activity reflect differences in autophagosome formation, correlating
      with the delivery of Atg9 to the PAS. Finally, this phosphorylation regulates
      Atg9 interaction with Atg23 and Atg27. 

PMID- 27050456
TI  - Inhibition of BMI1 induces autophagy-mediated necroptosis.
AB  - The clonal self-renewal property conferred by BMI1 is instrumental in maintenance
      of not only normal stem cells but also cancer-initiating cells from several
      different malignancies that represent a major challenge to chemotherapy.
      Realizing the immense pathological significance, PTC-209, a small molecule
      inhibitor of BMI1 transcription has recently been described. While targeting BMI1
      in various systems significantly decreases clonal growth, the mechanisms differ,
      are context-dependent, and somewhat unclear. We report here that genetic or
      pharmacological inhibition of BMI1 significantly impacts clonal growth without
      altering CDKN2A/INK4/ARF or CCNG2 and induces autophagy in ovarian cancer (OvCa)
      cells through ATP depletion. While autophagy can promote survival or induce cell
      death, targeting BMI1 engages the PINK1-PARK2-dependent mitochondrial pathway and
      induces a novel mode of nonapoptotic, necroptosis-mediated cell death. In OvCa,
      necroptosis is potentiated by activation of the RIPK1-RIPK3 complex that
      phosphorylates its downstream substrate, MLKL. Importantly, genetic or
      pharmacological inhibitors of autophagy or RIPK3 rescue clonal growth in BMI1
      depleted cells. Thus, we have established a novel molecular link between BMI1,
      clonal growth, autophagy and necroptosis. In chemoresistant OvCa where apoptotic
      pathways are frequently impaired, necroptotic cell death modalities provide an
      important alternate strategy that leverage overexpression of BMI1. 

PMID- 27050457
TI  - Distinct temporal requirements for autophagy and the proteasome in yeast meiosis.
AB  - Meiosis is a special type of cellular renovation that involves 2 successive cell
      divisions and a single round of DNA replication. Two major degradation systems,
      the autophagy-lysosome and the ubiquitin-proteasome, are involved in meiosis, but
      their roles have yet to be elucidated. Here we show that autophagy mainly affects
      the initiation of meiosis but not the nuclear division. Autophagy works not only
      by serving as a dynamic recycling system but also by eliminating some negative
      meiotic regulators such as Ego4 (Ynr034w-a). In a quantitative proteomics study,
      the proteasome was found to be significantly upregulated during meiotic
      divisions. We found that proteasomal activity is essential to the 2 successive
      meiotic nuclear divisions but not for the initiation of meiosis. Our study
      defines the roles of autophagy and the proteasome in meiosis: Autophagy mainly
      affects the initiation of meiosis, whereas the proteasome mainly affects the 2
      successive meiotic divisions. 

PMID- 27050458
TI  - Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy.
AB  - Mitochondrial fragmentation due to imbalanced fission and fusion of mitochondria
      is a prerequisite for mitophagy, however, the exact "coupling" of mitochondrial
      dynamics and mitophagy remains unclear. We have previously identified that FUNDC1
      recruits MAP1LC3B/LC3B (LC3) through its LC3-interacting region (LIR) motif to
      initiate mitophagy in mammalian cells. Here, we show that FUNDC1 interacts with
      both DNM1L/DRP1 and OPA1 to coordinate mitochondrial fission or fusion and
      mitophagy. OPA1 interacted with FUNDC1 via its Lys70 (K70) residue, and mutation
      of K70 to Ala (A), but not to Arg (R), abolished the interaction and promoted
      mitochondrial fission and mitophagy. Mitochondrial stress such as selenite or
      FCCP treatment caused the disassembly of the FUNDC1-OPA1 complex while enhancing
      DNM1L recruitment to the mitochondria. Furthermore, we observed that
      dephosphorylation of FUNDC1 under stress conditions promotes the dissociation of
      FUNDC1 from OPA1 and association with DNM1L. Our data suggest that FUNDC1
      regulates both mitochondrial fission or fusion and mitophagy and mediates the
      "coupling" across the double membrane for mitochondrial dynamics and quality
      control. 

PMID- 27050459
TI  - Mechanisms regulating proteostasis are involved in sympatric speciation of the
      blind mole rat, Spalax galili.
AB  - Genome-wide analysis demonstrates extensive genomic adaptive complexes involved
      in sympatric speciation between blind mole rats (Spalax galili) in abutting
      populations living in basalt and chalk soils. Among the gene ontology (GO)
      enrichment, musculature and metabolism stood out in basalt dwellers while
      nutrition and neurogenetics were highlighted in chalk residents. Measurements of
      mechanisms regulating protein homeostasis inspired by these GO terms suggest that
      at the proteomic level there is also a habitat/soil-type driven divergence with
      the basalt residents exhibiting higher proteasome activity whereas elevated
      levels of markers of autophagy are evident in the chalk inhabitants. 

PMID- 27050460
TI  - TARDBP/TDP-43 regulates autophagy in both MTORC1-dependent and MTORC1-independent
      manners.
AB  - In a recent paper we addressed the mechanism by which defective autophagy
      contributes to TARDBP/TDP-43-mediated neurodegenerative disorders. We
      demonstrated that TARDBP regulates MTORC1-TFEB signaling by targeting
      RPTOR/raptor, a key component and an adaptor protein of MTORC1. Loss of TARDBP
      decreased the mRNA stability of RPTOR and this regulation in turn enhanced
      autophagosomal and lysosomal biogenesis in an MTORC1-dependent manner. Meanwhile,
      loss of TARDBP could also impair autophagosome-lysosome fusion in an MTORC1
      independent manner. Importantly, we found that modulation of MTOR activity by
      treatment with rapamycin and phosphatidic acid had strong effects on the
      neurodegenerative phenotypes of TBPH (Drosophila TARDBP)-depleted flies. Taken
      together, our data reveal that multiple dysfunctions in the autophagic process
      contribute to TARDBP-linked neurodegeneration and may help to identify potential
      therapeutic targets in the future. 

PMID- 27050461
TI  - Emerging role of mammalian autophagy in ketogenesis to overcome starvation.
AB  - Autophagy is essential for the survival of lower organisms under conditions of
      nutrient depletion. However, whether autophagy plays a physiological role in
      mammals experiencing starvation is unknown. Ketogenesis is critical for
      overcoming starvation in mammals. We recently revealed that hepatic and renal
      autophagy are involved in starvation-induced ketogenesis, by utilizing tissue
      specific autophagy-deficient mouse models. The liver is the principal organ to
      regulate ketogenesis, and a deficiency of liver-specific autophagy partially but
      significantly attenuates starvation-induced ketogenesis. While deficiency of
      renal-specific autophagy does not affect starvation-induced ketogenesis, mice
      with deficiency of both liver and kidney autophagy have even lower blood ketone
      levels and physical activity under starvation conditions than those lacking
      autophagy in the liver alone. These results suggest that the kidney can
      compensate for impaired hepatic ketogenesis. Since ketone bodies are catabolized
      from fatty acids, the uptake of fatty acids, the formation of intracellular lipid
      droplets, and fatty acid oxidation are critical for ketogenesis. We found that
      starvation-induced lipid droplet formation is impaired in autophagy-deficient
      organs. Thus, hepatic and renal autophagy are required for starvation-induced
      ketogenesis. This process is essential for maintaining systemic energy
      homeostasis and physical activity during starvation. Our findings provide a novel
      insight into mammalian autophagy and the physiology of starvation. 

PMID- 27050462
TI  - A new role for ATM in selective autophagy of peroxisomes (pexophagy).
AB  - Peroxisomes are autonomously replicating and highly metabolic organelles
      necessary for beta-oxidation of fatty acids, a process that generates large
      amounts of reactive oxygen species (ROS). Maintaining a balance between
      biogenesis and degradation of peroxisomes is essential to maintain cellular redox
      balance, but how cells do this has remained somewhat of a mystery. While it is
      known that peroxisomes can be degraded via selective autophagy (pexophagy),
      little is known about how mammalian cells regulate pexophagy to maintain
      peroxisome homeostasis. We have uncovered a mechanism for regulating pexophagy in
      mammalian cells that defines a new role for ATM (ATM serine/threonine kinase)
      kinase as a "first responder" to peroxisomal ROS. ATM is delivered to the
      peroxisome by the PEX5 import receptor, which recognizes an SRL sequence located
      at the C terminus of ATM to localize this kinase to peroxisomes. In response to
      ROS, the ATM kinase is activated and performs 2 functions: i) it signals to AMPK,
      which activates TSC2 to suppresses MTORC1 and phosphorylates ULK1 to induce
      autophagy, and ii) targets specific peroxisomes for pexophagy by phosphorylating
      PEX5 at Ser141, which triggers ubiquitination of PEX5 at Lys209 and binding of
      the autophagy receptor protein SQSTM1/p62 to induce pexophagy.

PMID- 27050463
TI  - Identification of modulators of autophagic flux in an image-based high content
      siRNA screen.
AB  - Autophagy is the primary process for recycling cellular constituents through
      lysosomal degradation. In addition to nonselective autophagic engulfment of
      cytoplasm, autophagosomes can recognize specific cargo by interacting with
      ubiquitin-binding autophagy receptors such as SQSTM1/p62 (sequestosome 1). This
      selective form of autophagy is important for degrading aggregation-prone proteins
      prominent in many neurodegenerative diseases. We carried out a high content image
      based siRNA screen (4 to 8 siRNA per gene) for modulators of autophagic flux by
      monitoring fluorescence of GFP-SQSTM1 as well as colocalization of GFP-SQSTM1
      with LAMP2 (lysosomal-associated membrane protein 2)-positive lysosomal vesicles.
      GFP-SQSTM1 and LAMP2 phenotypes of primary screen hits were confirmed in 2 cell
      types and profiled with image-based viability and MTOR signaling assays. Common
      seed analysis guided siRNA selection for these assays to reduce bias toward off
      target effects. Confirmed hits were further validated in a live-cell assay to
      monitor fusion of autophagosomes with lysosomes. Knockdown of 10 targets resulted
      in phenotypic profiles across multiple assays that were consistent with
      upregulation of autophagic flux. These hits include modulators of transcription,
      lysine acetylation, and ubiquitination. Two targets, KAT8 (K[lysine]
      acetyltransferase 8) and CSNK1A1 (casein kinase 1, alpha 1), have been implicated
      in autophagic regulatory feedback loops. We confirmed that CSNK1A1 knockout (KO)
      cell lines have accelerated turnover of long-lived proteins labeled with (14)C
      leucine in a pulse-chase assay as additional validation of our screening assays.
      Data from this comprehensive autophagy screen point toward novel regulatory
      pathways that might yield new therapeutic targets for neurodegeneration. 

PMID- 27050464
TI  - Autophagy--A free meal in sickness-associated anorexia.
AB  - Activation of the immune system is metabolically costly, yet a hallmark of an
      infection is a reduction in appetite with a subsequent reduction in metabolite
      provision. What is the functional value of decreasing nutrient intake when an
      infection imposes large demands on metabolic parameters? Here, we propose that
      sickness-associated anorexia (SAA) upregulates the ancient process of autophagy
      systemically, thereby profoundly controlling not only immune- but also nonimmune
      competent cells. This allows an advanced impact on the resolution of an infection
      through direct pathogen killing, enhancement of epitope presentation and the
      contribution toward the clearance of noxious factors. By rendering a 'free meal,'
      autophagy is thus most fundamentally harnessed during an anorexic response in
      order to promote both host tolerance and resistance. These findings strongly
      suggest a reassessment of numerous SAA-related clinical applications and a re
      evaluation of current efforts in patient care. 

PMID- 27050466
TI  - Corrigendum.

PMID- 27050465
TI  - Corrigendum.

PMID- 27050468
TI  - Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral
      Nerve Abnormality.
AB  - OBJECTIVE: To compare rates of microvascular complications in adolescents with
      type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII)
      versus multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: Prospective
      cohort of 989 patients (aged 12-20 years; diabetes duration >5 years) treated
      with CSII or MDI for >12 months. Microvascular complications were assessed from
      2000-14: early retinopathy (seven-field fundal photography), peripheral nerve
      function (thermal and vibration threshold testing), autonomic nerve abnormality
      (heart rate variability analysis of electrocardiogram recordings) and albuminuria
      (albumin creatinine ratio/timed overnight albumin excretion). Generalized
      estimating equations (GEE) were used to examine the relationship between
      treatment and complications rates, adjusting for socio-economic status (SES) and
      known risk factors including HbA1c and diabetes duration. RESULTS: Comparing CSII
      with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7),
      retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07),
      peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve
      abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was
      associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45-0.95, p = 0.029)
      and peripheral nerve abnormality (OR 0.63, 95% CI 0.42-0.95, p = 0.026), but not
      albuminuria (OR 0.46, 95% CI 0.10-2.17, p = 0.33). SES was not associated with
      any of the complication outcomes. CONCLUSIONS: In adolescents, CSII use is
      associated with lower rates of retinopathy and peripheral nerve abnormality,
      suggesting an apparent benefit of CSII over MDI independent of glycemic control
      or SES.

PMID- 27050470
TI  - The search for therapeutic options for Middle East Respiratory Syndrome (MERS).

PMID- 27050469
TI  - Independent Candidate Serum Protein Biomarkers of Response to Adalimumab and to
      Infliximab in Rheumatoid Arthritis: An Exploratory Study.
AB  - Response to treatment of rheumatoid arthritis shows large inter-individual
      variability. This heterogeneity is observed with all the anti-rheumatic drugs,
      including the commonly used TNF inhibitors. It seems that drug-specific and
      target-specific factors lead individual patients to respond or not to a given
      drug, although this point has been challenged. The search of biomarkers
      distinguishing responders from non-responders has included shotgun proteomics of
      serum, as a previous study of response to infliximab, an anti-TNF antibody. Here,
      we have used the same study design and technology to search biomarkers of
      response to a different anti-TNF antibody, adalimumab, and we have compared the
      results obtained for the two anti-TNF drugs. Search of biomarkers of response to
      adalimumab included depletion of the most abundant serum proteins, 8-plex
      isobaric tag for relative and absolute quantitation (iTRAQ) labeling, two
      dimensional liquid chromatography fractionation and relative quantification with
      a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were
      identified in all the samples with at least 2 peptides and 95% confidence. Nine
      proteins showed differences between non-responders and responders (P < 0.05),
      representing putative biomarkers of response to adalimumab. These results were
      compared with the previous study of infliximab. Surprisingly, the non
      responder/responder differences in the two studies were not correlated (rs =
      0.07; P = 0.40). This overall independence with all the proteins showed two
      identifiable components. On one side, the putative biomarkers of response to
      either adalimumab or infliximab, which were not shared and showed an inverse
      correlation (rs = -0.69; P = 0.0023). On the other, eight proteins showing
      significant non-responder/responder differences in the analysis combining data of
      response to the two drugs. These results identify new putative biomarkers of
      response to treatment of rheumatoid arthritis and indicate that they are notably
      drug-specific. 

PMID- 27050471
TI  - Back to solitude: Solving the phylogenetic position of the Diazonidae using
      molecular and developmental characters.
AB  - The order Aplousobranchia (Chordata, Ascidiacea) contains approximately 1500
      species distributed worldwide. Their phylogeny, however, remains unclear, with
      unresolved family relationships. While most Aplousobranchia are colonial, debates
      exist concerning the phylogenetic position of families such as the Diazonidae and
      Cionidae, which exhibit a solitary lifestyle and share morphological
      characteristics with both Aplousobranchia and Phlebobranchia orders. To clarify
      the phylogenetic position of the Diazonidae and Cionidae, we determined the
      complete mitochondrial sequence of the solitary diazonid Rhopalaea idoneta. The
      phylogenetic reconstruction based on the 13 mitochondrial protein coding genes
      strongly supports a positioning of Diazonidae well-nested within the
      Aplousobranchia rather than a positioning as a sister clade of the
      Aplousobranchia. In addition, we examined the regenerative ability of R. idoneta.
      Similar to colonial Aplousobranchia, R. idoneta was found to be able to
      completely regenerate its thorax. Ciona, also known to possess high regenerative
      abilities, is the Aplousobranchia sister clade rather than a member of the
      Phlebobranchia. Our results thus indicate that the colonial lifestyle was
      acquired in the Aplousobranchia, starting from a Ciona-like solitary ancestor and
      secondarily lost in Diazonidae representatives such as Rhopalaea. The solitary
      lifestyle of Rhopalaea is thus a derived characteristic rather than an ancestral
      trait.

PMID- 27050472
TI  - Mesophilic and thermophilic anaerobic co-digestion of winery wastewater sludge
      and wine lees: An integrated approach for sustainable wine production.
AB  - In this work, winery wastes generated by a cellar producing approximately 300,000
      hL of wine per year was monitored for a period of one year. On average, 196 L of
      wastewater, 0.1 kg of waste activated sludge (dry matter) and 1.6 kg of wine lees
      were produced per hectoliter of wine produced. Different winery wastes, deriving
      from different production steps, namely waste activated sludge from wastewater
      treatment and wine lees, were co-treated using an anaerobic digestion process.
      Testing was conducted on a pilot scale for both mesophilic and thermophilic
      conditions. The process was stable for a long period at 37  degrees C, with an
      average biogas production of 0.386 m3/kg CODfed. On the other hand, for
      thermophilic conditions, volatile fatty acids accumulated in the reactor and the
      process failed after one hydraulic retention time (23 days). In order to fix the
      biological process, trace elements (iron, cobalt and nickel) were added to the
      feed of the thermophilic reactor. Metals augmentation improved process stability
      and yields at 55  degrees C. The pH ranged between 7.8 and 8.0, and specific gas
      production was 0.450 m3/kg CODfed, which corresponded to dry matter and COD
      removals of 34% and 88%, respectively. Although the observed performances in
      terms of biogas production were good, the thermophilic process exhibited some
      limitations related to both the necessity of metals addition and the worse
      dewaterability properties. In fact, while the mesophilic digestates reached a
      good dewatering quality via the addition of 6.5 g of polymer per kg of dry
      matter, the required dosage for the thermophilic sludge was greater than 10 g/kg
      of dry matter.

PMID- 27050473
TI  - Carotid artery intima-media thickness associated with prognosis of intracranial
      branch atheromatous disease.
AB  - BACKGROUND AND PURPOSE: Small deep brain infarcts are often caused by two
      different vascular pathologies: branch atheromatous disease (BAD) and
      lipohyalinotic degeneration (LD). In this study, we compare the clinical
      characteristics of BAD and LD and investigate the role of C-reactive protein
      (CRP), homocysteine (Hcy), and carotid artery intima-media thickness (IMT) in the
      prognosis of patients with BAD and LD. METHODS: Of 262 adult patients with small
      deep infarcts, 104 were considered BAD and 158 were considered LD. Data compared
      included clinical information, prevalence of lacune and leukoaraiosis, Hcy, CRP,
      carotid artery IMT, deterioration during admission, and recurrence of ischemic
      stroke (IS) within 1 year. RESULTS: Patients with LD have severe leukoaraiosis
      and higher prevalence of lacune and intracerebral hemorrhage compared with those
      with BAD. Patients with BAD have higher initial National Institutes of Health
      Stroke Scale scores and incidence of progressive motor deficits compared with
      those with LD; CRP is associated with the progression in both groups. There is no
      statistical difference of recurring risk of IS within 1 year between the two
      groups; by multivariable logistic regression analysis, carotid artery IMT was an
      independent risk factor for recurrence of IS in 1 year in patients with BAD.
      CONCLUSION: BAD as an independent clinical entity has different clinical and
      radiological characteristics compared with LD. Carotid artery IMT is an
      independent risk factor for recurrence of IS in patients with BAD.

PMID- 27050474
TI  - The Paradox of Time Post-Pregnancy Loss: Three Things Not to Say When
      Communicating Social Support.
AB  - In this essay, I interrogate the role time plays in the three most common social
      support messages I received post-pregnancy loss. In doing so, I illustrate how
      our most common "social support" responses to pregnancy loss, while uttered from
      caring, intentional places of support, can actually serve to marginalize and
      invalidate experiences of pregnancy loss.

PMID- 27050475
TI  - Predictors and longitudinal course of cognitive functioning in schizophrenia
      spectrum disorders, 10years after baseline: The OPUS study.
AB  - BACKGROUND: Identifying baseline predictors of the long-term course of cognitive
      functioning in schizophrenia spectrum disorders is important because of
      associations between cognitive functioning (CF) and functional outcome.
      Determining whether CF remains stable or change during the course of illness is
      another matter of interest. METHODS: Participants from The Danish OPUS Trial,
      aged 18-45years, with a baseline ICD-10 schizophrenia spectrum diagnosis, were
      assessed on psychopathology, social and vocational functioning at baseline, and
      cognitive functioning 5 (N=298) and 10years (N=322) after baseline. Uni- and
      multi-variable regression analyses of potential baseline predictors of 10-year CF
      were performed. Also, changes in CF and symptomatology between 5 and 10years of
      follow-up were assessed. FINDINGS: Baseline predictors of impaired CF after
      10years included male gender, unemployment, poor premorbid achievement and later
      age of onset. Having finished high school and receiving early intervention
      treatment was associated with better CF. Age, growing up with both parents,
      number of family and friends, primary caregivers education, premorbid social
      function, negative symptoms, GAF (symptoms, function) and substance abuse, were
      associated with CF in univariable analyses. Non-participants generally suffered
      from more severe dysfunction. Longitudinally, amelioration in negative symptoms
      was associated with improved speed of processing and executive functions. Symptom
      scores generally improved with time, while scores for all cognitive tests
      remained stable. CONCLUSION: The current study identifies several robust
      associations between baseline characteristics and 10-year cognitive outcome.
      Several other variables were univariably associated with 10-year cognitive
      outcome. Also, we found evidence for stability of CF over time.

PMID- 27050476
TI  - Risk factors for antipsychotic medication non-adherence behaviors and attitudes
      in adult-onset psychosis.
AB  - BACKGROUND: Research on antipsychotic medication non-adherence in first-episode
      psychosis patients tends to examine non-adherence behaviors and attitudes
      together. Nonetheless, attitudes do not always directly translate into behaviors.
      We examined the baseline predictors for antipsychotics non-adherence behaviors
      and attitudes separately in a first-episode psychosis cohort. We also included
      cognitive impairments as one of the predictor variables as this domain is rarely
      explored in adherence studies. METHOD: Participants were 313 adult-onset
      psychosis patients recruited from the Jockey Club Early Psychosis project in Hong
      Kong. Demographic, premorbid, clinical, and cognitive characteristics were first
      assessed at baseline. Six months later, participants completed a 14-item
      Medication Compliance Questionnaire, which was a modified and Cantonese
      translated version of the Medication Adherence Rating Scale that includes items
      pertaining to both adherence behaviors and attitudes. RESULTS: Rates of poor
      adherence behaviors and negative adherence attitudes were 17.6% and 27.8%,
      respectively. Determinants of poor adherence behavior included more severe
      positive symptoms, hospitalization at onset of illness, and poorer engagement in
      extended social network. As for negative adherence attitude, determinants
      included more severe general psychopathology, poorer insight, more psychic
      medication side-effects, and poorer performance on backward digit span test and
      WAIS-R information test. CONCLUSIONS: The risk factors for non-adherence
      behaviors and attitudes are different and they should all be taken into careful
      consideration while formulating appropriate intervention programs to tackle the
      adherence problem in adult onset psychosis.

PMID- 27050477
TI  - Transitive inference deficits in unaffected biological relatives of schizophrenia
      patients.
AB  - Currently available treatments have limited efficacy in remediating cognitive
      impairment in schizophrenia. Efforts to facilitate cognition-enhancing drug
      discovery recommend the use of varied experimental cognitive paradigms (including
      relational memory) as assessment tools in clinical drug trials. Although
      relational memory deficits are increasingly being recognized as a reliable
      cognitive marker of schizophrenia, relational memory performance among unaffected
      biological relatives remains unknown. Therefore, we evaluated 73 adolescents or
      young adults (22 first- and 26 second-degree relatives of schizophrenia patients
      and 25 healthy controls (HC)) using a well-validated transitive inference (TI)
      experimental paradigm previously used to demonstrate relational memory impairment
      in schizophrenia. We found that TI deficits were associated with schizophrenia
      risk with first-degree relatives showing greater impairment than second-degree
      relatives. First-degree relatives had poorer TI performance with significantly
      lower accuracy and longer response times than HC when responding to TI probe
      pairs. Second-degree relatives had significantly quicker response times than
      first-degree relatives and were more similar to HC in TI performance. We further
      explored the relationships between TI performance and neurocognitive domains
      implicated in schizophrenia. Among HC, response times were inversely correlated
      with FSIQ, verbal learning, processing speed, linguistic abilities and working
      memory. In contrast, relatives (first-degree in particular) had a differing
      pattern of TI-neurocognition relationships, which suggest that different brain
      circuits may be used when relatives encode and retrieve relational memory. Our
      finding that unaffected biological relatives of schizophrenia patients have TI
      deficits lends further support for the use of relational memory construct in
      future pro-cognition drug studies.

PMID- 27050478
TI  - Adherence to current recommendations on the use of methotrexate in rheumatoid
      arthritis in Italy: results from the MARI study.
AB  - OBJECTIVES: The aim of this study was to assess how the management of rheumatoid
      arthritis (RA) with methotrexate (MTX) in Italy is adherent to current national
      recommendations. METHODS: We performed a cross-sectional and retrospective
      analysis of data collected from the MARI study, a multicentre survey on Italian
      patients with RA on treatment with MTX for at least 12 months. Retrospective data
      included patient's clinical history, previous treatment with MTX, screening tests
      performed before MTX prescription. Cross-sectional data were collected about
      current treatment with MTX, concomitant medications, and disease activity. Each
      proposition of the 2013 Italian recommendations on the use of MTX in RA was
      reformulated in terms of audit criteria, and adherence to provided indications
      was evaluated for every patient. RESULTS: Among the 1336 included patients, less
      than 40% had started treatment with MTX within 3-6 months from the diagnosis and
      nearly 30% of them were prescribed with an initial dose of MTX between 12.5 and
      15 mg/week. Screening for HBV and HCV infection as well as chest x-ray was
      performed in a proportion of patients around 60% and more than 90% of them
      underwent lab tests before MTX prescription and regularly throughout the
      treatment. Folic acid supplementation was given at recommended dosages in a high
      proportion of patients. CONCLUSIONS: Our survey showed a good adherence of
      Italian rheumatologists to recommendations regarding safety issues with MTX in
      RA, but a suboptimal approach in terms of time and dosage of the treatment in the
      early phases of the disease.

PMID- 27050479
TI  - Targeted mutagenesis in chicken using CRISPR/Cas9 system.
AB  - The CRISPR/Cas9 system is a simple and powerful tool for genome editing in
      various organisms including livestock animals. However, the system has not been
      applied to poultry because of the difficulty in accessing their zygotes. Here we
      report the implementation of CRISPR/Cas9-mediated gene targeting in chickens. Two
      egg white genes, ovalbumin and ovomucoid, were efficiently (>90%) mutagenized in
      cultured chicken primordial germ cells (PGCs) by transfection of circular
      plasmids encoding Cas9, a single guide RNA, and a gene encoding drug resistance,
      followed by transient antibiotic selection. We transplanted CRISPR-induced mutant
      ovomucoid PGCs into recipient chicken embryos and established three germline
      chimeric roosters (G0). All of the roosters had donor-derived mutant-ovomucoid
      spermatozoa, and the two with a high transmission rate of donor-derived gametes
      produced heterozygous mutant ovomucoid chickens as about half of their donor
      derived offspring in the next generation (G1). Furthermore, we generated
      ovomucoid homozygous mutant offspring (G2) by crossing the G1 mutant chickens.
      Taken together, these results demonstrate that the CRISPR/Cas9 system is a simple
      and effective gene-targeting method in chickens. 

PMID- 27050480
TI  - Perioperative Acute Kidney Injury-Reply.

PMID- 27050481
TI  - Optimization of Isomaltooligosaccharide Size Distribution by Acceptor Reaction of
      Weissella confusa Dextransucrase and Characterization of Novel alpha-(1->2)
      Branched Isomaltooligosaccharides.
AB  - Long-chain isomaltooligosaccharides (IMOs) are promising prebiotics. IMOs were
      produced by a Weissella confusa dextransucrase via maltose acceptor reaction. The
      inputs of substrates (i.e., sucrose and maltose, 0.15-1 M) and dextransucrase (1
      10 U/g sucrose) were used to control IMO yield and profile. According to response
      surface modeling, 1 M sucrose and 0.5 M maltose were optimal for the synthesis of
      longer IMOs, whereas the dextransucrase dosage showed no significant effect. In
      addition to the principal linear IMOs, a homologous series of minor IMOs were
      also produced from maltose. As identified by MS(n) and NMR spectroscopy, the
      minor trisaccharide contained an alpha-(1->2)-linked glucosyl residue on the
      reducing residue of maltose and thus was alpha-d-glucopyranosyl-(1->2)-[alpha-d
      glucopyranosyl-(1->4)]-d-glucopyranose (centose). The higher members of the
      series were probably formed by the attachment of a single unit branch to linear
      IMOs. This is the first report of such alpha-(1->2)-branched IMOs produced from
      maltose by a dextransucrase. 

PMID- 27050482
TI  - Methylation polymorphism influences practice effects in children during attention
      tasks.
AB  - Epigenetic mechanisms mediate the influence of experience on gene expression.
      Methylation is a principal method for inducing epigenetic effects on DNA. In this
      paper, we examine alleles of the methylenetetrahydrofolate reductase (MTHFR) gene
      that vary enzyme activity, altering the availability of the methyl donor and thus
      changing the efficiency of methylation. We hypothesized that alleles of the MTHFR
      gene would influence behavior in an attention-related task in conjunction with
      genes known to influence attention. We found that seven-year-old children
      homozygous for the C allele of MTHFR in interaction with the catechol O
      methyltransferase (COMT) gene showed greater improvement in overall reaction time
      (RT) and in conflict resolution with practice on the Attention Network Test
      (ANT). This finding indicates that methylation may operate on or through genes
      that influence executive network operation. However, MTHFR T allele carriers
      showed faster overall RT and conflict resolution. Some children showed an initial
      improvement in ANT RT followed by a decline in performance, and we found that
      alleles of the dopamine beta-hydroxylase (DBH) gene were related to this
      performance decline. These results suggest a genetic dissociation between
      improvement while learning a skill and reduction in performance with continued
      practice.

PMID- 27050483
TI  - Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the
      uptake of NOD2 ligands in macrophages.
AB  - Macropinocytosis can be induced in several cell types by stimulation with growth
      factors. In selected cell types, notably macrophages and dendritic cells,
      macropinocytosis occurs constitutively, supporting the uptake of antigens for
      subsequent presentation. Despite their different mode of initiation and
      contrasting physiological roles, it is tacitly assumed that both types of
      macropinocytosis are mechanistically identical. We report that constitutive
      macropinocytosis is stringently calcium dependent, while stimulus-induced
      macropinocytosis is not. Extracellular calcium is sensed by G-protein-coupled
      calcium-sensing receptors (CaSR) that signal macropinocytosis through Galpha-,
      phosphatidylinositol 3-kinase and phospholipase C. These pathways promote the
      recruitment of exchange factors that stimulate Rac and/or Cdc42, driving actin
      dependent formation of ruffles and macropinosomes. In addition, the heterologous
      expression of CaSR in HEK293 cells confers on them the ability to perform
      constitutive macropinocytosis. Finally, we show that CaSR-induced constitutive
      macropinocytosis facilitates the sentinel function of macrophages, promoting the
      efficient delivery of ligands to cytosolic pattern-recognition receptors. 

PMID- 27050484
TI  - Synthesis, characterization and evaluation of two crosslinked polymeric resins
      and their comparison with walnut shell in oil removal from water.
AB  - The aim of this paper was to compare two kinds of adsorbents (walnut shell and
      polymeric resins) in terms of their efficiency to remove oil from water, since
      walnut shell losses weight during the process requiring interruption, while
      polymeric resins do not. Polymeric resins based on glycidyl methacrylate and
      divinylbenzene (GMA-DVB) and styrene and divinylbenzene (STY-DVB) were
      synthesized and characterized. All adsorbents were tested by continuous flow
      process, eluting 3,000 bed volumes of synthetic oily water, and the oil content
      was monitored by fluorescence spectroscopy. Although the walnut shell presented
      high efficiency (~94%), STY-DVB was even better (~100%) besides presenting better
      mechanical resistance. Moreover, polymeric resins, mainly when based on GMA, can
      be chemically modified to remove specific contaminants still remaining in water
      after conventional treatment. 

PMID- 27050485
TI  - Abdominal regional in-situ perfusion in donation after circulatory determination
      of death donors.
AB  - PURPOSE OF REVIEW: Provide an overview regarding the current state of abdominal
      regional perfusion (ARP) in donation after circulatory determination of death
      (DCD) organ transplantation, including the principles behind how ARP functions
      and the most recent results of its clinical application. RECENT FINDINGS: ARP has
      been applied clinically in DCD at both hypothermic and normothermic temperatures.
      The use of hypothermic perfusion has primarily been limited to DCD kidney
      transplantation, whereas normothermic regional perfusion has been used to improve
      and assess the quality of DCD kidneys, livers, and even a handful of pancreata
      for transplantation. Results of recent single-center series reflect acceptable
      rates of early graft function and survival using grafts that might have otherwise
      been discarded. SUMMARY: ARP is an important form of donor maintenance that helps
      improve DCD organ viability and may help expand the applicability of
      transplantation using organs arising through this process.

PMID- 27050487
TI  - Inertial and stick-slip regimes of unstable adhesive tape peeling.
AB  - We present an experimental characterization of the detachment front unstable
      dynamics observed during the peeling of pressure sensitive adhesives. We use an
      experimental set-up specifically designed to control the peeling angle theta and
      the peeled tape length L, while peeling an adhesive tape from a flat substrate at
      a constant driving velocity V. High-speed imaging allows us to report the
      evolution of the period and amplitude of the front oscillations, as well as the
      relative durations of their fast and slow phases, as a function of the control
      parameters V, L and theta. Our study shows that, as the driving velocity or the
      peeling angle increases, the oscillations of the peeling front progressively
      evolve from genuine "stick-slip" oscillations, made of alternating long stick
      phases and very brief slip phases, to sinusoidal oscillations of amplitude twice
      the peeling velocity. We propose a model which, taking into account the peeling
      angle-dependent kinetic energy cost to accelerate and decelerate the peeled tape,
      explains the transition from the "stick-slip" to the "inertial" regime of the
      dynamical instability. Using independent direct measurements of the effective
      fracture energy of the adhesive-substrate joint, we show that our model
      quantitatively accounts for the two regimes of the unstable dynamics.

PMID- 27050486
TI  - The size of the EB cap determines instantaneous microtubule stability.
AB  - The function of microtubules relies on their ability to switch between phases of
      growth and shrinkage. A nucleotide-dependent stabilising cap at microtubule ends
      is thought to be lost before this switch can occur; however, the nature and size
      of this protective cap are unknown. Using a microfluidics-assisted multi-colour
      TIRF microscopy assay with close-to-nm and sub-second precision, we measured the
      sizes of the stabilizing cap of individual microtubules. We find that the
      protective caps are formed by the extended binding regions of EB proteins. Cap
      lengths vary considerably and longer caps are more stable. Nevertheless, the
      trigger of instability lies in a short region at the end of the cap, as a
      quantitative model of cap stability demonstrates. Our study establishes the
      spatial and kinetic characteristics of the protective cap and provides an insight
      into the molecular mechanism by which its loss leads to the switch from
      microtubule growth to shrinkage. 

PMID- 27050488
TI  - The bright and dark side of Joseph Fenton: An analysis of narratives describing
      the man known as Sudharman.
AB  - The death of Joe "Sudharman" Fenton sparked competing narratives leaving some
      members of the family wondering who Joe Fenton was, the man who died as
      Sudharman. During the night of July 4, 2010, Sudharman was murdered as he slept
      in his yoga studio in Union County, Pennsylvania. This piece examines his death
      in order to examine how communication was used to describe Joe Fenton. We used
      autoethnographic and ethnographic methods to collect the media coverage of his
      death, the funeral remembrances, and the blog posts, as well as completed two in
      depth interviews with family members in order to find out who Joe Fenton was. We
      analyzed how others described Fenton through the frames of dark and bright
      communication behaviors. Our analysis determined that Fenton was seen in a
      spiritual/religious light, as he was described as god-like, a shining beacon and
      memorable. Dark communication described Fenton as being manipulative, deceitful,
      and, at times, emotionally abusive.

PMID- 27050489
TI  - The Prevalence of Incidentally Detected Idiopathic Misty Mesentery on
      Multidetector Computed Tomography: Can Obesity Be the Triggering Cause?
AB  - PURPOSE: Misty mesentery appearance is commonly reported in daily practice,
      usually as a secondary finding of various pathological entities, but sometimes it
      is encountered as an isolated finding that cannot be attributed to any other
      disease entity. We aimed to assess the prevalence of cases with incidentally
      detected idiopathic misty mesentery on computed tomography (CT) and to summarize
      the pathologies leading to this appearance. METHODS: Medical records and initial
      and follow-up CT features of patients with misty mesentery appearance between
      January 2011 and January 2013 were analysed. The study included cases with no
      known cause of misty mesentery according to associated CT findings, clinical
      history, or biochemical manifestations, and excluded patients with diseases known
      to cause misty mesentery, lymph nodes greater than a short-axis diameter of 5 mm,
      discrete mesenteric masses, or bowel wall thickening. RESULTS: There were a total
      of 561 patients in whom misty mesentery appearance was depicted on abdominopelvic
      CT scans. A total of 80 cases were found to have isolated incidental idiopathic
      misty mesentery, giving a prevalence of 7%. The common indication for CT
      examination was abdominal pain. There was a slight female predominance (51.3%).
      67.5% of all patients were classified as obese and 17.5% as overweight.
      CONCLUSIONS: The results of the present study show that idiopathic incidental
      misty mesentery appearance has a significant prevalence. Also, the high body mass
      index of these patients and the growing evidence of obesity-induced inflammatory
      changes in adipose tissue are suggestive of an association between obesity and
      misty mesentery appearance on CT.

PMID- 27050491
TI  - Graphene-like Two-Dimensional Ionic Boron with Double Dirac Cones at Ambient
      Condition.
AB  - Recently, partially ionic boron (gamma-B28) has been predicted and observed in
      pure boron, in bulk phase and controlled by pressure [ Nature 2009 , 457 , 863 ].
      By using ab initio evolutionary structure search, we report the prediction of
      ionic boron at a reduced dimension and ambient pressure, namely, the two
      dimensional (2D) ionic boron. This 2D boron structure consists of graphene-like
      plane and B2 atom pairs with the P6/mmm space group and six atoms in the unit
      cell and has lower energy than the previously reported alpha-sheet structure and
      its analogues. Its dynamical and thermal stability are confirmed by the phonon
      spectrum and ab initio molecular dynamics simulation. In addition, this phase
      exhibits double Dirac cones with massless Dirac Fermions due to the significant
      charge transfer between the graphene-like plane and B2 pair that enhances the
      energetic stability of the P6/mmm boron. A Fermi velocity (vf) as high as 2.3 *
      10(6) m/s, which is even higher than that of graphene (0.82 * 10(6) m/s), is
      predicted for the P6/mmm boron. The present work is the first report of the 2D
      ionic boron at atmospheric pressure. The unique electronic structure renders the
      2D ionic boron a promising 2D material for applications in nanoelectronics.

PMID- 27050490
TI  - Functional characterization of hypothetical proteins of Mycobacterium
      tuberculosis with possible esterase/lipase signature: a cumulative in silico and
      in vitro approach.
AB  - The functional aspect of several mycobacterium proteins annotated as hypothetical
      are yet to be discovered. In the present investigation, in silico approaches were
      used to predict the biological function of some of the unknown Mtb proteins,
      which were further validated by wet lab experiments. After screening thousands of
      Mtb proteins, functionally unknown hypothetical proteins Rv0421c, Rv0519c,
      Rv0774c, Rv1191, Rv1592c, and Rv3591c were chosen on the basis of their
      importance in Mtb life cycle. All these proteins posses the alpha/beta-hydrolase
      topological fold, characteristic of lipases/esterases, with serine, aspartate,
      and histidine as the putative members of the catalytic triad. The catalytic
      serine is located in pentapeptide motif "GXSXG" and oxyanion residue is in
      dipeptide motif HG. To further support our observation, molecular docking was
      performed with conventional synthetic lipolytic substrates (pNP-esterss) and
      specific lipase/esterase inhibitors (tetrahydrolipstatin and
      phenylmethanesulfonyl fluoride (PMSF)). Significant docking score and strong
      interaction of substrates/inhibitors with these proteins revealed that these
      could be possible lipases/esterases. To validate the in silico studies, these
      genes were cloned from Mtb genome and the proteins were over-expressed in pQE
      30/Escherichia coli M15 system. The expressed proteins were purified to
      homogeneity and enzymatic activity was determined using pNP esters as substrate.
      The enzyme activity of recombinant proteins was inhibited by tetrahydrolipstatin
      and PMSF pre-treatment. Outcome of the present investigation provided a basic
      platform to analyze and characterize unknown hypothetical proteins.

PMID- 27050492
TI  - Optofluidic lens with low spherical and low field curvature aberrations.
AB  - This paper reports an optofluidic lens with low spherical and low field curvature
      aberrations through the desired refractive index profile by precisely controlling
      the mixing between ethylene glycol and deionized water in an optofluidic chip.
      The experimental results demonstrate that the spherical aberration is reduced to
      19.5 MUm and the full width at half maximum of the focal point is 7.8 MUm with a
      wide divergence angle of 35 degrees. In addition, the optofluidic lens can focus
      light at different off-axis positions on the focal plane with Deltax' < 6.8 MUm
      and at opposite transverse positions with |Deltay - Deltay'| < 5.7 MUm. This is
      the first demonstration of a special optofluidic lens that significantly reduces
      both the spherical and field curvature aberrations, which enhances the focusing
      power and facilitates multiple light source illumination using a single lens. It
      is anticipated to have high potential for applications such as on-chip light
      manipulation, sample illumination and multiplexed detection.

PMID- 27050493
TI  - [Working with hearing impairment: an integrated approach].
AB  - Patients with hearing impairment are more likely to encounter health problems and
      difficulties at work than their colleagues with normal hearing. This is often not
      realised by either patients or professionals. In this article we describe three
      cases that illustrate how working conditions can influence the health of workers
      with hearing loss. We have implemented a vocational enablement protocol that
      follows a multidisciplinary approach in order to meet these patients' needs. Due
      to a mismatch between the demands of a job and an individual's auditory
      capacities, even a mild hearing impairment can cause serious problems if a
      patient works in adverse conditions. In addition, in many workplaces the ability
      to hear well is a safety issue. Professionals have to be aware of both
      possibilities. Specialized centres offer good facilities and ensure the optimal
      transfer of insight into the working environment by involving an occupational
      physician in their team. 

PMID- 27050494
TI  - [Treatment in the Intensive Care Unit: continue or withdraw?].
AB  - End-of-life decision-making in the Intensive Care Unit is a common and complex
      process. The step-by-step process of decision-making leading to withdrawal of
      life-sustaining treatment is illustrated in this paper by a clinical case. A
      variety of factors influences the decision to adjust the initial curative
      treatment policy towards withdrawal of life-sustaining therapy and the pursuit of
      comfort care. For a smooth decision-making process, it is necessary to make a
      prognosis and obtain consensus amongst the healthcare team. Withdrawal of life
      sustaining treatment is ultimately a medical decision and a consensual decision
      should be reached by all medical staff and nurses, and preferably also by the
      patient and family. Timely involvement of a legal representative of the patient
      is essential for an uncomplicated decision-making process. Advance care planning
      and advance directives provide opportunities for patients to express their
      preferences beforehand. It is important to realise that end-of-life decisions are
      significantly influenced by personal and cultural values. 

PMID- 27050495
TI  - [When should notification of an infectious disease be mandatory? A decision aid
      to determine whether mandatory notification is justified].
AB  - In the Netherlands, all physicians are required to report cases of certain
      infectious diseases to the public health services, to allow appropriate control
      measures. In recent years, various requests have been submitted to add certain
      infectious diseases to the list of notifiable diseases. In order to decide
      whether such a request should be granted, we developed a structured decision aid
      based on a range of existing criteria for mandatory notification, applied in the
      Netherlands and other countries. In this article, we describe the development of
      this decision aid and illustrate its use in the mandatory notification
      application reviews for Vibrio vulnificus infection and tularaemia respectively.
      Based on the decision aid outcomes, mandatory notification for V. vulnificus
      infection was advised as not necessary whereas notification is considered
      mandatory for tularaemia. 

PMID- 27050496
TI  - [First combined intestinal and abdominal wall transplantation in the
      Netherlands].
AB  - BACKGROUND: When total parenteral nutrition (TPN) is not an option, intestinal
      transplantation is the sole treatment for patients with end-stage intestinal
      failure to increase the chance of long-term survival. However, in 20-33% of
      patients, abdominal wall-related complications occur after isolated intestinal
      transplantation. CASE DESCRIPTION: The patient is a 24-year-old woman with ultra
      short bowel syndrome, caused by a severely complicated history of Crohn's
      disease. After 5 years of TPN, the patient was referred for intestinal
      transplantation. In addition, an abdominal wall transplant was required due to an
      abdominal wall defect, extensive scarring of the abdominal wall and lack of free
      space within the abdomen. Therefore, a combined intestinal and abdominal wall
      transplantation was performed. Six months after transplantation the patient has a
      sufficient abdominal wall, a normal body mass index and no longer requires any
      feeding lines. CONCLUSION: This case report describes the first combined
      intestinal and abdominal wall transplantation in the Netherlands and in the
      Eurotransplant region in a patient with end-stage intestinal failure and loss of
      abdominal domain.

PMID- 27050497
TI  - [Micrographic surgery of lentigo maligna].
AB  - Lentigo maligna is an in situ melanoma which usually affects sun-damaged skin on
      the head and neck. In patients with lentigo maligna, the clinically visible
      demarcation often correlates poorly with the histopathologically confirmed
      demarcation. The standard treatment for lentigo maligna is excision with at least
      5 mm margins. The key disadvantage of regular excision is the lack of
      histological margin control, resulting in non-radical excisions and a higher risk
      of recurrence. Micrographic surgery is indicated for patients with lentigo
      maligna because this technique is tissue-sparing and it offers absolute certainty
      concerning the presence of clear histological margins. 

PMID- 27050498
TI  - [A boy with a painful tumour of his skull].
AB  - A 12-year-old boy presented with an increasing painful swelling of the skull.
      Physical examination revealed in the left parieto-occipital region a skin
      coloured solid mass of 2-3 cm in diameter. The X-ray of the skull was highly
      suspicious for Langerhans cell histiocytosis. Histopathology of a biopsy of the
      lesion confirmed the diagnosis. 

PMID- 27050499
TI  - Early Decompression (< 8 h) after Traumatic Cervical Spinal Cord Injury Improves
      Functional Outcome as Assessed by Spinal Cord Independence Measure after One
      Year.
AB  - There is an ongoing controversy about the optimal timing for surgical
      decompression after acute traumatic cervical spinal cord injury (SCI). For this
      reason, we performed a retrospective study of patients who were operated on after
      traumatic cervical SCI at the Trauma Center Murnau, Germany, and who met
      inclusion as well as exclusion criteria (n = 70 patients). Follow-up data were
      collected prospectively according to the European Multicenter Study about Spinal
      Cord Injury (EMSCI) protocol over a period of 1 year. Early decompression was
      defined as within the first 8 h after the insult (n = 35 patients). Primary
      outcome was the difference in the SCIM (Spinal Cord Independence Measure) 1 year
      after the trauma. After the follow-up period, patients who were decompressed
      earlier had a significantly higher SCIM difference (45.8 vs. 27.1, p < 0.005). A
      regression analysis showed that timing of decompression, age, as well as basal
      AIS (American Spinal Injury Association Impairment Scale) and basal SCIM scores
      were independent predictors for a better functional outcome (SCIM). Further,
      patients from the early decompression group had better AIS grades (p < 0.006) and
      a higher AIS conversion rate (p < 0.029). Additionally, this cohort also had a
      better total motor performance as well as upper extremity motor function after 1
      year (p < 0.025 and p < 0.002). The motor and neurological levels of patients who
      were operated on within 8 h were significantly more caudal (p < 0.003 and p <
      0.014) after 1 year. The present study suggests that early decompression after
      traumatic cervical SCI might have a positive impact on the functional and
      neurological outcome of affected individuals.

PMID- 27050500
TI  - Nano drug delivery systems and gamma radiation sterilization.
AB  - In recent years, drug delivery systems such as liposomes and microparticles have
      been used in clinic for the treatment of different diseases and from a regulatory
      point of view, a parenterally applied drug and drug delivery systems must be
      sterile and pyrogen free. Radiation sterilization is a method recognized by
      pharmacopoeias to achieve sterility criteria of parenterals. It has the ability
      to kill microorganisms in therapeutic products. The ability of, however,
      irradiation might also affect the performance of drug delivery systems. One of
      the most critical points is irradiation dose, because certain undesirable
      chemical and physical changes may accompany with the irradiation, especially with
      the traditionally applied dose of 25 kGy. Its ionizing property may cause
      fragmentation of covalent bond. The care must be paid to the applied dose. In
      this research, the effects of gamma irradiation on different drug delivery
      systems such as chitosan microparticles, liposomes, niosomes and sphingosomes
      were investigated. According to the experimental data, it can be concluded that
      gamma irradiation can be a suitable sterilization technique for liposome, niosome
      and sphingosome dispersions. When all irradiated drug carrier systems were taken
      into consideration, chitosan glutamate microparticles were found as the most
      radioresistant drug delivery system among the others.

PMID- 27050501
TI  - Protective Effects of Cerium Oxide Nanoparticles on MC3T3-E1 Osteoblastic Cells
      Exposed to X-Ray Irradiation.
AB  - BACKGROUND/AIMS: Exposure to ionizing radiation can result in bone damage,
      including decreased osteocyte number and suppressed osteoblastic activity.
      However, molecular mechanisms remain to be elucidated, and effective prevention
      strategies are still limited. This study was to investigate whether cerium oxide
      nanoparticles (CeO2 NP) can protect MC3T3-E1 osteoblast-like cells from damaging
      effects of X-ray irradiation, and to study the underpinning mechanism(s).
      METHODS: MC3T3-E1, a osteoblast-like cell line, was exposed to X-ray irradiation
      and treated with different concentration of CeO2 nanoparticles. The micronucleus
      frequency was counted under a fluorescence microscope. Cell viability was
      evaluated using MTT assay. The effects of irradiation and CeO2 nanoparticles on
      alkaline phosphatase activity and MC3T3-E1 mineralization were further assayed.
      RESULTS: We found that the ratio of micronuclei to binuclei was dose-dependently
      increased with X-ray irradiation (from 2 to 6 Gy), but diminished with the
      increased concentration of CeO2 NP treatment (from 50 to 100 nM). Exposure to X
      rays (6 Gy) decreased cell viability, differentiation and the mineralization, but
      CeO2 NP treatment (100 nM) attenuated the deteriorative effects of irradiation.
      Both intracellular reactive oxygen species (ROS) production and extracellular
      H2O2 concentration were increased after X-ray irradiation, but reduced following
      CeO2 NP treatment. Similar to irradiation, exposure to H2O2 (10 uM) elevated the
      frequency of micronuclei and diminished cell viability and mineralization, while
      these changes were ameliorated following CeO2 NP treatment. CONCLUSIONS: Taken
      together, our findings suggest that CeO2 nanoparticles exhibit astonishing
      protective effects on irradiation-induced osteoradionecrosis in MC3T3-E1 cells,
      and the protective effects appear to be mediated, at least partially, by reducing
      oxidative stress.

PMID- 27050502
TI  - Molecular Crowding Affects the Conformational Fluctuations, Peroxidase Activity,
      and Folding Landscape of Yeast Cytochrome c.
AB  - To understand how a protein folds and behaves inside living cells, the effects of
      synthetic crowding media on protein folding, function, stability, and association
      have been studied in detail. Because the effect of excluded volume is more
      prominent in an extended state than in the native protein, a majority of these
      studies have been conducted in the unfolded state of different model proteins.
      Here, we have used fluorescence correlation spectroscopy (FCS) and other
      biophysical methods to investigate the effect of crowding agents Ficoll70 and
      Dextran70 on the nativelike state of cytochrome c from yeast. Yeast cytochrome c
      (y-cytc) contains a substantial expanded state in its native folded condition,
      which is present in equilibrium with a compact conformer in aqueous buffer. We
      have found that the crowding medium affects the native state equilibrium between
      compact and expanded states, shifting its population toward the compact
      conformer. As a result, the peroxidase activity of y-cytc decreases. Urea-induced
      protein stability measurements show that the compaction destabilizes the protein
      due to charge repulsions between similar charged clusters. Interestingly, the
      time constant of conformational fluctuations between the compact and expanded
      conformers has been found to increase in the crowded milieu, suggesting a crucial
      role of the solution microviscosity.

PMID- 27050503
TI  - Production and characterization of recombinant human acid alpha-glucosidase in
      transgenic rice cell suspension culture.
AB  - Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid
      alpha-glucosidase (GAA), a glycogen-degrading lysosomal enzyme. In this study,
      the human GAA cDNA gene was synthesized from human placenta cells and cloned into
      a plant expression vector under the control of the rice alpha-amylase 3D (RAmy3D)
      promoter. The plant expression vector was introduced into rice calli (Oryza
      sativa L. cv. Dongjin) mediated by Agrobacterium tumefaciens. Genomic DNA PCR and
      Northern blot analysis were used to determine the integration and mRNA expression
      of the hGAA gene in the putative transgenic rice cells. SDS-PAGE and Western blot
      analysis showed that the glycosylated precursor recombinant hGAA had a molecular
      mass of 110kDa due to the presence of seven N-glycosylation sites. The
      accumulation of hGAA protein in the culture medium was approximately 37mg/L after
      11 days of culturing in a sugar depletion medium. The His tagged-hGAA protein was
      purified using an Ni-NTA column and confirmed as the precursor form of hGAA
      without the signal peptide encoded by the cDNA on the N-terminal amino acid
      sequence. The acid alpha-glucosidase activity of hGAA produced in transgenic rice
      cells gave results similar to those of the enzyme produced by CHO cells. 

PMID- 27050504
TI  - Biphasic cultivation strategy to avoid Epo-Fc aggregation and optimize protein
      expression.
AB  - In biphasic cultivations, the culture conditions are initially kept at an optimum
      for rapid cell growth and biomass accumulation. In the second phase, the culture
      is shifted to conditions ensuring maximum specific protein production and the
      protein quality required. The influence of specific culture parameters is cell
      line dependent and their impact on product quality needs to be investigated. In
      this study, a biphasic cultivation strategy for a Chinese hamster ovary (CHO)
      cell line expressing an erythropoietin fusion protein (Epo-Fc) was developed.
      Cultures were run in batch mode and after an initial growth phase, cultivation
      temperature and pH were shifted. Applying a DoE (Design of Experiments) approach,
      a fractional factorial design was used to systematically evaluate the influence
      of cultivation temperature and pH as well as their synergistic effect on cell
      growth as well as on recombinant protein production and aggregation. All three
      responses were influenced by the cultivation temperature. Additionally, an
      interaction between pH and temperature was found to be related to protein
      aggregation. Compared with the initial standard conditions of 37 degrees C and pH
      7.05, a parameter shift to low temperature and acidic pH resulted in a decrease
      in the aggregate fraction from 75% to less than 1%. Furthermore, the synergistic
      effect of temperature and pH substantially lowered the cell-specific rates of
      glucose and glutamine consumption as well as lactate and ammonium production. The
      optimized culture conditions also led to an increase of the cell-specific rates
      of recombinant Epo-Fc production, thus resulting in a more economic bioprocess. 

PMID- 27050505
TI  - Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic
      kidney disease among hypertensive patients?
AB  - BACKGROUND: Hypertension is one of the important contributing factors linked with
      both causation and development of kidney disease. It is a multifactorial,
      polygenic, and complex disorder due to interaction of several risk genes with
      environmental factors. The present study was aimed to explore genetic
      polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients.
      METHODS: Three hundred patients were enrolled in the study. Ninety were
      hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients
      without CKD were taken as controls. Demographic data including age, sex, Body
      mass index (BMI), and other risk factors were also recorded. DNA was extracted
      from blood by salting out method. Genotyping of ACE gene was done by PCR
      technique. All the statistical analysis was done by using Epi Info and SPSS
      version 16 software (SPSS Inc., Chicago, IL). RESULTS: Mean age was higher in the
      control group (p < 0.05). Variables among two groups were compared out of which
      age, BMI, hemoglobin (Hb) was found to be statistically significant whereas other
      variables like systolic blood pressure, triglyceride and low-density lipoprotein
      were not. Blood urea and serum creatinine levels were statistically significant
      in the two genotypes (p < 0.05). Total and HDL cholesterol were statistically
      significant for DD genotype of ACE gene (OR = 1.42, 95% CI = 0.72-2.81).
      Similarly, the risk for CKD among hypertensive patients was also associated with
      D allele of ACE gene (OR = 1.25, 95% CI = 0.86-1.79). CONCLUSION: It is concluded
      that ACE-DD genotype may be a risk factor for the causation and development of
      chronic kidney failure among hypertensive patients.

PMID- 27050506
TI  - Agreement between current and active asthma classification methods, Asthma Call
      back Survey, 2011-2012.
AB  - OBJECTIVE: Various approaches have been developed to identify persons with asthma
      using survey data. To assess agreement between current and active asthma
      classifications, 2011-2012 Asthma Call-back Survey landline telephone household
      data from 38 states, District of Columbia, and Puerto Rico for adults aged >=18
      years who have ever been told by a health professional they have asthma were
      analyzed. METHODS: Respondents were classified to have current asthma if they
      reported still having asthma, and active asthma if they reported within the past
      year: 1) talking to a doctor about asthma, 2) taking asthma medication, or 3)
      having any symptoms of asthma. Agreement between classifications was assessed
      using the Kappa statistic. RESULTS: Among adults ever told by a health
      professional they have asthma, an estimated 72% had current asthma and 75% had
      active asthma. Overall, 67% of individuals met classifications of both current
      and active asthma and 20% had neither current nor active asthma (Kappa = 0.68).
      The Kappa increased to 0.72 when talking to a doctor about asthma was removed
      from the active asthma classification. CONCLUSIONS: Results indicated substantial
      agreement between current and active asthma. Agreement was strengthened when
      talking to a doctor about asthma was removed from the active asthma
      classification.

PMID- 27050507
TI  - Tocilizumab in patients with Takayasu arteritis: a retrospective study and
      literature review.
AB  - OBJECTIVES: To assess the efficacy of tocilizumab (TCZ) in patients with Takayasu
      arteritis (TA). METHODS: Multicentre open-label retrospective study. RESULTS:
      Eight patients (all women) with a mean age of 34+/-16 years, median 36 years
      (range: 7-57) were assessed. The main clinical features at TCZ therapy onset
      were: constitutional symptoms (n=4), fever (n=3), headache (n=2), chest pain
      (n=1), abdominal pain (n=1), mesenteric ischaemia (n=1), myalgia involving the
      lower limbs (n=1), cerebral vascular insufficiency (n=1), malaise (n=1), upper
      limb claudication (n=1) and nodular scleritis (n=1). Besides corticosteroids and
      before TCZ treatment onset, 7 of 8 patients had also received several
      conventional immunosuppressive and/or biologic agents. Seven patients experienced
      marked clinical improvement in the first 3 months after the onset of TCZ therapy.
      After a median follow-up of 15.5 [interquartile range-IQR: 12-24] months, 7
      patients were asymptomatic. The median C-reactive protein decreased from 3.09
      [IQR: 0.5-12] to 0.15 [IQR: 0.1-0.5] mg/dL (p=0.018), and median erythrocyte
      sedimentation rate from 40 [IQ range: 28-72] to 3 [IQR: 2-5] mm/1st hour
      (p=0.012). The median dose of prednisone was also tapered from 42.5 [IQR: 25-50]
      to 2.5 [IQR: 0-7.5] mg/day (p=0.011). However, TCZ had to be discontinued in 1
      patient because she developed a systemic lupus erythematosus, and in another
      patient due to inefficiency. TCZ dose was reduced in a patient because of mild
      thrombocytopenia. CONCLUSIONS: TCZ appears to be effective in the management of
      patients with TA, in particular in patients refractory to corticosteroids and/or
      conventional immunosuppressive drugs.

PMID- 27050508
TI  - Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse
      Formation by Repressing Neurexin in Postmitotic Neurons.
AB  - Proneural proteins of the class I/II basic-helix-loop-helix (bHLH) family are
      highly conserved transcription factors. Class I bHLH proteins are expressed in a
      broad number of tissues during development, whereas class II bHLH protein
      expression is more tissue restricted. Our understanding of the function of class
      I/II bHLH transcription factors in both invertebrate and vertebrate neurobiology
      is largely focused on their function as regulators of neurogenesis. Here, we show
      that the class I bHLH proteins Daughterless and Tcf4 are expressed in postmitotic
      neurons in Drosophila melanogaster and mice, respectively, where they function to
      restrict neurite branching and synapse formation. Our data indicate that
      Daughterless performs this function in part by restricting the expression of the
      cell adhesion molecule Neurexin. This suggests a role for these proteins outside
      of their established roles in neurogenesis.

PMID- 27050509
TI  - Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity.
AB  - Successful immunogenic apoptosis in experimental cancer therapy depends on the
      induction of strong host anti-tumor responses. Given that tumors are often
      resistant to apoptosis, it is important to identify alternative molecular
      mechanisms that elicit immunogenic cell death. We have developed a genetic model
      in which direct dimerization of FADD combined with inducible expression of RIPK3
      promotes necroptosis. We report that necroptotic cancer cells release damage
      associated molecular patterns and promote maturation of dendritic cells, the
      cross-priming of cytotoxic T cells, and the production of IFN-gamma in response
      to tumor antigen stimulation. Using both FADD-dependent and FADD-independent
      RIPK3 induction systems, we demonstrate the efficient vaccination potential of
      immunogenic necroptotic cells. Our study broadens the current concept of
      immunogenic cell death and opens doors for the development of new strategies in
      cancer therapy. 

PMID- 27050510
TI  - H3K4me3 Demethylase Kdm5a Is Required for NK Cell Activation by Associating with
      p50 to Suppress SOCS1.
AB  - The H3K4me3 demethylase Kdm5a regulates gene transcription and is implicated in
      carcinogenesis. However, the role of Kdm5a in innate immune response remains
      poorly understood. Here, we demonstrate that Kdm5a deficiency impairs activation
      of natural killer (NK) cells, with decreased IFN-gamma production. Accordingly,
      Kdm5a(-/-) mice are highly susceptible to Listeria monocytogenes (Lm) infection.
      During NK cell activation, loss of Kdm5a profoundly impairs phosphorylation and
      nuclear localization of STAT4, along with increased expression of suppressor of
      cytokine signaling 1 (SOCS1). Mechanistic studies reveal that Kdm5a associates
      with p50 and binds to the Socs1 promoter region in resting NK cells, leading to a
      substantial decrease in H3K4me3 modification and repressive chromatin
      configuration at the Socs1 promoter. Thus, Kdm5a is required for priming
      activation of NK cells by suppressing the suppressor, SOCS1. Our study provides
      insights into the epigenetic regulation of innate immune response of NK cells. 

PMID- 27050511
TI  - Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose
      Triacylglycerol Lipase and FoxO Proteins.
AB  - Metabolism is a highly integrated process that is coordinately regulated between
      tissues and within individual cells. FoxO proteins are major targets of insulin
      action and contribute to the regulation of gluconeogenesis, glycolysis, and
      lipogenesis in the liver. However, the mechanisms by which FoxO proteins exert
      these diverse effects in an integrated fashion remain poorly understood. We
      report that FoxO proteins also exert important effects on intrahepatic lipolysis
      and fatty acid oxidation via the regulation of adipose triacylglycerol lipase
      (ATGL), which mediates the first step in lipolysis, and its inhibitor, the G0/S1
      switch 2 gene (G0S2). We also find that ATGL-dependent lipolysis plays a critical
      role in mediating diverse effects of FoxO proteins in the liver, including
      effects on gluconeogenic, glycolytic, and lipogenic gene expression and
      metabolism. These results indicate that intrahepatic lipolysis plays a critical
      role in mediating and integrating the regulation of glucose and lipid metabolism
      downstream of FoxO proteins. 

PMID- 27050512
TI  - Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.
AB  - The known link between obesity and cancer suggests an important interaction
      between the host lipid metabolism and tumorigenesis. Here, we used a syngeneic
      tumor graft model to demonstrate that tumor development influences the host lipid
      metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by
      stimulating very low-density lipoprotein (VLDL) production and blunting VLDL and
      low-density lipoprotein (LDL) turnover. To assess whether tumor progression was
      dependent on tumor-induced hyperlipidemia, we utilized the VLDL production
      deficient mouse model, carboxylesterase3/triacylglycerol hydrolase (Ces3/TGH)
      knockout mice. In Ces3/Tgh(-/-) tumor-bearing mice, plasma triglyceride and
      cholesterol levels were attenuated. Importantly tumor weight was reduced in
      Ces3/Tgh(-/-) mice. Mechanistically, reduced tumor growth in Ces3/Tgh(-/-) mice
      was attributed to reversal of tumor-induced PCSK9-mediated degradation of hepatic
      LDLR and decrease of LDL turnover. Our data demonstrate that tumor-induced
      hyperlipidemia encompasses a feed-forward loop that reprograms hepatic
      lipoprotein homeostasis in part by providing LDL cholesterol to support tumor
      growth. 

PMID- 27050513
TI  - An Essential Role for Liver ERalpha in Coupling Hepatic Metabolism to the
      Reproductive Cycle.
AB  - Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms
      underpinning this regulation and the role of the hepatic estrogen receptor alpha
      (ERalpha) in cholesterol physiology are unclear. Utilizing a mouse model
      involving selective ablation of ERalpha in the liver, we demonstrate that hepatic
      ERalpha couples lipid metabolism to the reproductive cycle. We show that this
      receptor regulates the synthesis of cholesterol transport proteins, enzymes for
      lipoprotein remodeling, and receptors for cholesterol uptake. Additionally,
      ERalpha is indispensable during proestrus for the generation of high-density
      lipoproteins efficient in eliciting cholesterol efflux from macrophages. We
      propose that a specific interaction with liver X receptor alpha (LXRalpha)
      mediates the broad effects of ERalpha on the hepatic lipid metabolism. 

PMID- 27050514
TI  - Differential Mitochondrial Requirements for Radially and Non-radially Migrating
      Cortical Neurons: Implications for Mitochondrial Disorders.
AB  - Mitochondrial dysfunction has been increasingly linked to neurodevelopmental
      disorders such as intellectual disability, childhood epilepsy, and autism
      spectrum disorder, conditions also associated with cortical GABAergic interneuron
      dysfunction. Although interneurons have some of the highest metabolic demands in
      the postnatal brain, the importance of mitochondria during interneuron
      development is unknown. We find that interneuron migration from the basal
      forebrain to the neocortex is highly sensitive to perturbations in oxidative
      phosphorylation. Both pharmacologic and genetic inhibition of adenine nucleotide
      transferase 1 (Ant1) disrupts the non-radial migration of interneurons, but not
      the radial migration of cortical projection neurons. The selective dependence of
      cortical interneuron migration on oxidative phosphorylation may be a mechanistic
      pathway upon which multiple developmental and metabolic pathologies converge. 

PMID- 27050515
TI  - Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis.
AB  - Uhrf1 (also known as Np95) is a regulator of DNA methylation and histone
      ubiquitination and plays an important role in embryogenesis and tumorigenesis.
      Here, we report that Uhrf1 is essential for invariant natural killer T (iNKT)
      cell development. We found that Uhrf1 was significantly upregulated in stage 1
      iNKT cells. Targeted disruption of Uhrf1 resulted in stage 1-specific transition
      defects as observed by not only increased apoptosis, but also aberrant effector
      differentiation, which eventually led to the impaired generation of iNKT cells in
      Uhrf1-deficient mice. Notably, Uhrf1 deficiency resulted in attenuated activation
      of Akt-mTOR signaling in stage 1 iNKT cells and overexpression of active Akt
      rescued iNKT cell developmental defects. Collectively, our results suggest that
      Uhrf1 regulation of the Akt-mTOR signaling pathway is required for iNKT cell
      development. 

PMID- 27050516
TI  - Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A
      and Quantitative Phosphoproteomics.
AB  - Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8
      and CDK19. Using CA, we now report a large-scale identification of Mediator
      kinase substrates in human cells (HCT116). We identified over 16,000 quantified
      phosphosites including 78 high-confidence Mediator kinase targets within 64
      proteins, including DNA-binding transcription factors and proteins associated
      with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data
      correlated with Mediator kinase targets, the effects of CA on gene expression
      were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome
      analyses, tracking around 7,000 proteins across six time points (0-24 hr),
      revealed that CA selectively affected pathways implicated in inflammation,
      growth, and metabolic regulation. Contrary to expectations, increased turnover of
      Mediator kinase targets was not generally observed. Collectively, these data
      support Mediator kinases as regulators of chromatin and RNA polymerase II
      activity and suggest their roles extend beyond transcription to metabolism and
      DNA repair. 

PMID- 27050517
TI  - Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa.
AB  - Most retinitis pigmentosa (RP) mutations arise in rod photoreceptor genes,
      leading to diminished peripheral and nighttime vision. Using a pig model of
      autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment
      epithelium (RPE) and, thus, is not transported to photoreceptors. The resulting
      starvation for glucose metabolites impairs synthesis of cone visual pigment-rich
      outer segments (OSs), and then their mitochondrial-rich inner segments
      dissociate. Loss of these functional structures diminishes cone-dependent high
      resolution central vision, which is utilized for most daily tasks. By
      transplanting wild-type rods, to restore glucose transport, or directly replacing
      glucose in the subretinal space, to bypass its retention in the RPE, we can
      regenerate cone functional structures, reactivating the dormant cells. Beyond
      providing metabolic building blocks for cone functional structures, we show
      glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt
      signaling, thereby shunting metabolites toward aerobic glucose metabolism and
      regenerating cone OS synthesis.

PMID- 27050518
TI  - Mesolimbic Dopamine Encodes Prediction Errors in a State-Dependent Manner.
AB  - Mesolimbic dopamine encodes the benefits of a course of action. However, the
      value of an appetitive reward depends strongly on an animal's current state. To
      investigate the relationship between dopamine, value, and physiological state, we
      monitored sub-second dopamine release in the nucleus accumbens core while rats
      made choices between food and sucrose solution following selective satiation on
      one of these reinforcers. Dopamine signals reflected preference for the
      reinforcers in the new state, decreasing to the devalued reward and, after
      satiation on food, increasing for the valued sucrose solution. These changes were
      rapid and selective, with dopamine release returning to pre-satiation patterns
      when the animals were re-tested in a standard food-restricted state. Such rapid
      and selective adaptation of dopamine-associated value signals could provide an
      important signal to promote efficient foraging for a varied diet. 

PMID- 27050519
TI  - Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian
      Central Nervous System.
AB  - How aging impacts axon regeneration after CNS injury is not known. We assessed
      the impact of age on axon regeneration induced by Pten deletion in corticospinal
      and rubrospinal neurons, two neuronal populations with distinct innate
      regenerative abilities. As in young mice, Pten deletion in older mice remains
      effective in preventing axotomy-induced decline in neuron-intrinsic growth state,
      as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a
      spinal cord injury. However, axonal regeneration distal to injury is greatly
      diminished, accompanied by increased expression of astroglial and inflammatory
      markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent
      decline in axon regeneration, as revealed when neuron-intrinsic growth state is
      elevated. These results have important implications for developing strategies to
      promote axonal repair after CNS injuries or diseases, which increasingly affect
      middle-aged to aging populations. 

PMID- 27050520
TI  - Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co
      induce Axon Regrowth in the Adult Central Nervous System.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a transcription
      factor central to axon regrowth with an enigmatic ability to act in different
      subcellular regions independently of its transcriptional roles. However, its
      roles in mature CNS neurons remain unclear. Here, we show that along with nuclear
      translocation, STAT3 translocates to mitochondria in mature CNS neurons upon
      cytokine stimulation. Loss- and gain-of-function studies using knockout mice and
      viral expression of various STAT3 mutants demonstrate that STAT3's
      transcriptional function is indispensable for CNS axon regrowth, whereas
      mitochondrial STAT3 enhances bioenergetics and further potentiates regrowth.
      STAT3's localization, functions, and growth-promoting effects are regulated by
      mitogen-activated protein kinase kinase (MEK), an effect further enhanced by Pten
      deletion, leading to extensive axon regrowth in the mouse optic pathway and
      spinal cord. These results highlight CNS neuronal dependence on STAT3
      transcriptional activity, with mitochondrial STAT3 providing ancillary roles, and
      illustrate a critical contribution for MEK in enhancing diverse STAT3 functions
      and axon regrowth. 

PMID- 27050521
TI  - Leukemogenic MLL-ENL Fusions Induce Alternative Chromatin States to Drive a
      Functionally Dichotomous Group of Target Genes.
AB  - MLL fusions are leukemogenic transcription factors that enhance transcriptional
      elongation through modification of chromatin and RNA Pol II. Global transcription
      rates and chromatin changes accompanying the transformation process induced by
      MLL-ENL were monitored by nascent RNA-seq and ChIP-seq, revealing 165 direct
      target genes separated into two distinct clades. ME5 genes bound MLL-ENL at the
      promoter, relied on DOT1L-mediated histone methylation, and coded preferentially
      for transcription factors, including many homeobox genes. A distinct ME3 group
      accumulated MLL-ENL beyond the termination site, was dependent on P-TEFb-mediated
      phosphorylation of RNA Pol II for transcription, and translated mainly into
      proteins involved in RNA biology and ribosome assembly. This dichotomy was
      reflected by a differential sensitivity toward small molecule inhibitors,
      suggesting the possibility of a combinatorial strategy for treatment of MLL
      induced leukemia. 

PMID- 27050522
TI  - PAPERCLIP Identifies MicroRNA Targets and a Role of CstF64/64tau in Promoting Non
      canonical poly(A) Site Usage.
AB  - Accurate and precise annotation of 3' UTRs is critical for understanding how
      mRNAs are regulated by microRNAs (miRNAs) and RNA-binding proteins (RBPs). Here,
      we describe a method, poly(A) binding protein-mediated mRNA 3' end retrieval by
      crosslinking immunoprecipitation (PAPERCLIP), that shows high specificity for
      mRNA 3' ends and compares favorably with existing 3' end mapping methods.
      PAPERCLIP uncovers a previously unrecognized role of CstF64/64tau in promoting
      the usage of a selected group of non-canonical poly(A) sites, the majority of
      which contain a downstream GUKKU motif. Furthermore, in the mouse brain,
      PAPERCLIP discovers extended 3' UTR sequences harboring functional miRNA binding
      sites and reveals developmentally regulated APA shifts, including one in Atp2b2
      that is evolutionarily conserved in humans and results in the gain of a
      functional binding site of miR-137. PAPERCLIP provides a powerful tool to
      decipher post-transcriptional regulation of mRNAs through APA in vivo.

PMID- 27050523
TI  - Multiphasic and Dynamic Changes in Alternative Splicing during Induction of
      Pluripotency Are Coordinated by Numerous RNA-Binding Proteins.
AB  - Alternative splicing (AS) plays a critical role in cell fate transitions,
      development, and disease. Recent studies have shown that AS also influences
      pluripotency and somatic cell reprogramming. We profiled transcriptome-wide AS
      changes that occur during reprogramming of fibroblasts to pluripotency. This
      analysis revealed distinct phases of AS, including a splicing program that is
      unique to transgene-independent induced pluripotent stem cells (iPSCs). Changes
      in the expression of AS factors Zcchc24, Esrp1, Mbnl1/2, and Rbm47 were
      demonstrated to contribute to phase-specific AS. RNA-binding motif enrichment
      analysis near alternatively spliced exons provided further insight into the
      combinatorial regulation of AS during reprogramming by different RNA-binding
      proteins. Ectopic expression of Esrp1 enhanced reprogramming, in part by
      modulating the AS of the epithelial specific transcription factor Grhl1. These
      data represent a comprehensive temporal analysis of the dynamic regulation of AS
      during the acquisition of pluripotency. 

PMID- 27050524
TI  - Nascent DNA Proteomics Reveals a Chromatin Remodeler Required for Topoisomerase I
      Loading at Replication Forks.
AB  - During transcription and DNA replication, the DNA template is overwound ahead of
      RNA and DNA polymerases and relaxed by DNA topoisomerases. Inhibitors of
      topoisomerases are potent anti-cancer agents. Camptothecin traps topoisomerase I
      on DNA and exerts preferential cytotoxicity toward cancer cells by way of its
      interference with the progression of replication forks. Starting with an unbiased
      proteomic analysis, we find that the chromatin remodeling complex BAZ1B-SMARCA5
      accumulates near replication forks in camptothecin-exposed cells. We report that
      BAZ1B associates with topoisomerase I and facilitates its access to replication
      forks. Single-molecule analyses of replication structures show that BAZ1B
      contributes to replication interference by camptothecin. A lack of BAZ1B confers
      increased cellular tolerance of camptothecin. These findings reveal BAZ1B as a
      key facilitator of topoisomerase I function during DNA replication that affects
      the response of cancer cells to topoisomerase I inhibitors. 

PMID- 27050525
TI  - ERRalpha-Regulated Lactate Metabolism Contributes to Resistance to Targeted
      Therapies in Breast Cancer.
AB  - Imaging studies in animals and in humans have indicated that the oxygenation and
      nutritional status of solid tumors is dynamic. Furthermore, the extremely low
      level of glucose within tumors, while reflecting its rapid uptake and metabolism,
      also suggests that cancer cells must rely on other energy sources in some
      circumstances. Here, we find that some breast cancer cells can switch to
      utilizing lactate as a primary source of energy, allowing them to survive glucose
      deprivation for extended periods, and that this activity confers resistance to
      PI3K/mTOR inhibitors. The nuclear receptor, estrogen-related receptor alpha
      (ERRalpha), was shown to regulate the expression of genes required for lactate
      utilization, and isotopomer analysis revealed that genetic or pharmacological
      inhibition of ERRalpha activity compromised lactate oxidation. Importantly,
      ERRalpha antagonists increased the in vitro and in vivo efficacy of PI3K/mTOR
      inhibitors, highlighting the potential clinical utility of this drug combination.

PMID- 27050526
TI  - Manipulating TLR Signaling Increases the Anti-tumor T Cell Response Induced by
      Viral Cancer Therapies.
AB  - The immune response plays a key role in enhancing the therapeutic activity of
      oncolytic virotherapies. However, to date, investigators have relied on inherent
      interactions between the virus and the immune system, often coupled to the
      expression of a single cytokine transgene. Recently, the importance of TLR
      activation in mediating adaptive immunity has been demonstrated. We therefore
      sought to influence the type and level of immune response raised after oncolytic
      vaccinia therapy through manipulation of TLR signaling. Vaccinia naturally
      activates TLR2, associated with an antibody response, whereas a CTL response is
      associated with TLR3-TRIF-signaling pathways. We manipulated TLR signaling by
      vaccinia through deglycosylation of the viral particle to block TLR2 activation
      and expression of a TRIF transgene. The resulting vector displayed greatly
      reduced production of anti-viral neutralizing antibody as well as an increased
      anti-tumor CTL response. Delivery in both naive and pre-treated mice was enhanced
      and immunotherapeutic activity dramatically improved. 

PMID- 27050527
TI  - High-Content Quantification of Single-Cell Immune Dynamics.
AB  - Cells receive time-varying signals from the environment and generate functional
      responses by secreting their own signaling molecules. Characterizing dynamic
      input-output relationships in single cells is crucial for understanding and
      modeling cellular systems. We developed an automated microfluidic system that
      delivers precisely defined dynamical inputs to individual living cells and
      simultaneously measures key immune parameters dynamically. Our system combines
      nanoliter immunoassays, microfluidic input generation, and time-lapse microscopy,
      enabling study of previously untestable aspects of immunity by measuring time
      dependent cytokine secretion and transcription factor activity from single cells
      stimulated with dynamic inflammatory inputs. Employing this system to analyze
      macrophage signal processing under pathogen inputs, we found that the dynamics of
      TNF secretion are highly heterogeneous and surprisingly uncorrelated with the
      dynamics of NF-kappaB, the transcription factor controlling TNF production.
      Computational modeling of the LPS/TLR4 pathway shows that post-transcriptional
      regulation by TRIF is a key determinant of noisy and uncorrelated TNF secretion
      dynamics in single macrophages. 

PMID- 27050529
TI  - Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic
      Kidney Disease.
AB  - The varied functions of the kidneys are influenced by the complex process of
      aging. The glomerular filtration rate (GFR) steadily declines with normal aging,
      and the progress of this process can be influenced by superimposed diseases.
      Microscopically, nephron numbers decrease as global glomerulosclerosis becomes
      more evident. The precise mechanisms underlying nephron loss with aging are not
      well understood, but derangements in podocyte biology appear to be involved.
      Classifications of chronic kidney disease (CKD) incorporate GFR values and
      attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for
      defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive
      definition of CKD could offer a solution to this problem and more meaningfully
      capture the prognostic implications of CKD. 

PMID- 27050528
TI  - The success of microneedle-mediated vaccine delivery into skin.
AB  - Microneedles (MNs) are designed to specifically target the outermost, skin
      barrier layer, the stratum corneum, creating transient pathways for minimally
      invasive transcutaneous delivery. It is reported that MNs can facilitate delivery
      without stimulating the pain receptors or damaging blood vessels that lie
      beneath, thus being perceived as painless and associated with reduced bleeding.
      This immunocompetence of the skin, coupled with its ease of access, makes this
      organ an attractive vaccination site. The purpose of this review was to collate
      primary scientific literature pertaining to MN-mediated in vivo vaccination
      programmes. A total of 62 original research articles are presented, compiling
      vaccination strategies in 6 different models (mouse, rat, guinea pig, rabbit,
      pig, macaque and human). Vaccines tested span a wide range of viral, bacterial
      and protozoan pathogens and includes 7 of the 13 vaccine-preventable diseases, as
      defined by the WHO. This review highlights the paucity of available clinical
      trial data. MN-delivered vaccines have demonstrated safety and immunogenicity in
      pre-clinical models and boast desirable attributes such as painless
      administration, thermostability, dose-sparing capacity and the potential for self
      administration. These advantages should contribute to enhanced global vaccine
      access.

PMID- 27050530
TI  - Letter in response to: "Hyperglycemia is a risk factor for high-grade
      envenomations after European viper bites (Vipera spp.) in children".

PMID- 27050531
TI  - The Diagnostic Accuracy and Clinical Utility of Three Noninvasive Models for
      Predicting Liver Fibrosis in Patients with HBV Infection.
AB  - AIM: To evaluate the diagnostic accuracy and clinical utility of the fibrosis
      index based on the four factors (FIB-4), aspartate aminotransferase -to-platelet
      ratio index (APRI), and aspartate aminotransferase-alanine aminotransferase ratio
      index (AAR) for predicting liver fibrosis in patients with HBV infection.
      METHODS: From January 2006 to December 2010,a total of 1543 consecutive chronic
      hepatitis B(CHB) patients who underwent liver biopsies were enrolled. FIB-4,APRI,
      and AAR were calculated.The areas under the receiver-operating characteristic
      curves (AUROCs) were calculated to assess the diagnostic accuracy of these
      models.The AUROCs of these models were compared by DeLong's test.For further
      comparisons in different studies,the AUROCs were adjusted to conduct Adjusted
      AUROCs(ADjAUROCs) according to the prevalence of fibrosis stages using the
      difference between advanced and nonadvanced fibrosis (DANA). RESULTS: For
      prediction of significant fibrosis,severe fibrosis,and cirrhosis,the AUROCs of
      FIB-4 were 0.646(ADjAUROC 0.717),0.670(ADjAUROC 0.741), and 0.715(ADjAUROC 0.786)
      respectively;whereas it were 0.656(ADjAUROC 0.727),0.653(ADjAUROC 0.724) and
      0.639(ADjAUROC 0.710) for APRI, 0.498(ADjAUROC 0.569),0.548(ADjAUROC 0.619) and
      0.573(ADjAUROC 0.644) for AAR. The further comparisons demonstrated that there
      were no significant differences of AUROCs between FIB-4 and APRI in predicting
      significant and severe fibrosis(P > 0.05),while FIB-4 was superior to APRI in
      predicting cirrhosis(P < 0.001). Further subgroup analysis demonstrated that the
      diagnostic accuracy of FIB-4 and APRI in patients with normal alanine
      aminotransferase(ALT) were higher than that in patients with elevated ALT.
      CONCLUSIONS: The results demonstrated that FIB-4 and APRI are useful for
      diagnosis of fibrosis. FIB-4 and APRI have similar diagnostic accuracy in
      predicting significant and severe fibrosis,while FIB-4 is superior to APRI in
      predicting cirrhosis. The clinical utility of FIB-4 and APRI for fibrosis need
      further external validation in a large population before it was used for
      prediction of fibrosis in patients with HBV infection.

PMID- 27050532
TI  - Contemplative pedagogy in hybrid and asynchronous online undergraduate aging
      services/gerontology courses.
AB  - The rapid aging of the U.S. population has brought with it the challenge of
      preparing effective leaders in aging services/policy. These leaders need a fresh
      cognitive and empathic understanding of the complex needs of older adults and
      those who work with them. With its experiential and integrative approach,
      contemplative pedagogies are ideally suited for preparing aging services leaders.
      Contemplative pedagogies help learners interact with course material in ways that
      deeply engage students, disrupt habitual ways of thinking, and encourage
      innovative approaches to aging services/policy issues. Given the increasing
      popularity of hybrid and online courses, contemplative pedagogies could enhance
      learners' satisfaction with and the quality of learning in these courses. This
      article provides a description of contemplative pedagogies and embodied cognition
      research and theory as a theoretical framework for them. The article discusses
      the ways in that contemplative pedagogies have been incorporated in two
      undergraduate management of aging services courses. Student responses to the use
      of contemplative pedagogies and directions for future research are presented.

PMID- 27050533
TI  - Optimization of nanostructured lipid carriers for topical delivery of nimesulide
      using Box-Behnken design approach.
AB  - OBJECTIVE: The aim of the present study was to develop and optimize topically
      applied nimesulide-loaded nanostructured lipid carriers. MATERIALS AND METHODS:
      Box-Behnken experimental design was applied for optimization of nanostructured
      lipid carriers. The independent variables were ratio of stearic acid: oleic acid
      (X1), poloxamer 188 concentration (X2) and lecithin concentration (X3) while
      particle size (Y1) and entrapment efficiency (Y2) were the chosen responses.
      Further, skin penetration study, in vitro release, confocal laser scanning
      microscopy and stability study were also performed. RESULTS AND DISCUSSION: The
      optimized nanostructured lipid carriers of nimesulide provide reasonable particle
      size, flux, and entrapment efficiency. Optimized formulation (F9) with mean
      particle size of 214.4 +/- 11 nm showed 89.4 +/- 3.40% entrapment efficiency and
      achieved mean flux 2.66 +/- 0.09 MUg/cm2/h. In vitro release study showed
      prolonged drug release from the optimized formulation following Higuchi release
      kinetics with R2 value of 0.984. Confocal laser scanning microscopy revealed an
      enhanced penetration of Rhodamine B-loaded nanostructured lipid carriers to the
      deeper layers of the skin. The stability study confirmed that the optimized
      formulation was considerably stable at refrigerator temperature as compared to
      room temperature. CONCLUSION: Our results concluded that nanostructured lipid
      carriers are an efficient carrier for topical delivery of nimesulide.

PMID- 27050534
TI  - Measuring reactive hyperemia in the lower limb using near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) has been used to measure reactive hyperemia
      following a vascular occlusion. However, the procedures and methods of analysis
      used have varied. The purpose of the present study is to identify reproducible
      methods for measuring reactive hyperemia using HbO2 NIRS signals in the calf and
      foot. Healthy participants (10 male, 10 female) aged 19 to 28 years performed one
      of two tests: reproducibility trials or elevation protocol (30 and 60 cm limb
      elevation above the heart). The time to 50% reperfusion (T1/2) and the second
      (R2q) quartile rates of reperfusion were found to be the most reproducible
      parameters (coefficient of variation= 7.12 to 14.1%). The time to 95% reperfusion
      (T95) was 12.7% more reproducible on average than the previously reported
      parameter of time to peak hyperemia. Measures of reperfusion time and rate slowed
      with increasing limb elevation. Correlations were identified between the calf and
      foot in the measurements of R2q (R2 = 0.713, p = 0.021), T1/2 (R2 = 0.673, p =
      0.033), and T95 (R2 = 0.792, p = 0.006). Half and 95% recovery times and second
      and third quartile rates expressed good reproducibility and sensitivity to change
      with reduced perfusion pressure. NIRS measures of reactive hyperemia have the
      potential to evaluate microvascular perfusion in clinical populations.

PMID- 27050535
TI  - Toward more intuitive brain-computer interfacing: classification of binary covert
      intentions using functional near-infrared spectroscopy.
AB  - In traditional brain-computer interface (BCI) studies, binary communication
      systems have generally been implemented using two mental tasks arbitrarily
      assigned to "yes" or "no" intentions (e.g., mental arithmetic calculation for
      "yes"). A recent pilot study performed with one paralyzed patient showed the
      possibility of a more intuitive paradigm for binary BCI communications, in which
      the patient's internal yes/no intentions were directly decoded from functional
      near-infrared spectroscopy (fNIRS). We investigated whether such an "fNIRS-based
      direct intention decoding" paradigm can be reliably used for practical BCI
      communications. Eight healthy subjects participated in this study, and each
      participant was administered 70 disjunctive questions. Brain hemodynamic
      responses were recorded using a multichannel fNIRS device, while the participants
      were internally expressing "yes" or "no" intentions to each question. Different
      feature types, feature numbers, and time window sizes were tested to investigate
      optimal conditions for classifying the internal binary intentions. About 75% of
      the answers were correctly classified when the individual best feature set was
      employed (75.89% +/- 1.39 and 74.08% +/- 2.87 for oxygenated and deoxygenated
      hemoglobin responses, respectively), which was significantly higher than a random
      chance level (68.57% for p < 0.001). The kurtosis feature showed the highest mean
      classification accuracy among all feature types. The grand-averaged hemodynamic
      responses showed that wide brain regions are associated with the processing of
      binary implicit intentions. Our experimental results demonstrated that direct
      decoding of internal binary intention has the potential to be used for
      implementing more intuitive and user-friendly communication systems for patients
      with motor disabilities.

PMID- 27050536
TI  - Assessment of MOF's Quality: Quantifying Defect Content in Crystalline Porous
      Materials.
AB  - A quantitative method for assessment of defects in metal-organic framework (MOF)
      is presented based on isotherms calculated using Grand Canonical Monte Carlo
      (GCMC) simulations. Defects in MOF structures generated during the synthesis and
      sample preparation can lead to large variations in experimentally measured
      adsorption isotherms but are difficult to quantify. We use as a case study CO2
      adsorption on Cu3(BTC)2 MOF (BTC = benzene-1,3,5-tricarboxylic acid) to show that
      different samples reported in the literature have various proportions of
      principal pores blocked or side pores blocked, resulting in isotherms with
      different capacity and affinity toward CO2. The approach presented is easily
      generalized to other materials, showing that simulation results combined with
      experimentally measured gas adsorption isotherms can be used to quantitatively
      identify key defective features of the material. 

PMID- 27050537
TI  - Complexity, Predictability and Time Homogeneity of Syntax in the Songs of
      Cassin's Vireo (Vireo cassinii).
AB  - Many species of animals deliver vocalizations in sequences presumed to be
      governed by internal rules, though the nature and complexity of these syntactical
      rules have been investigated in relatively few species. Here I present an
      investigation into the song syntax of fourteen male Cassin's Vireos (Vireo
      cassinii), a species whose song sequences are highly temporally structured. I
      compare their song sequences to three candidate models of varying levels of
      complexity-zero-order, first-order and second-order Markov models-and employ
      novel methods to interpolate between these three models. A variety of analyses,
      including sequence simulations, Fisher's exact tests, and model likelihood
      analyses, showed that the songs of this species are too complex to be described
      by a zero-order or first-order Markov model. The model that best fit the data was
      intermediate in complexity between a first- and second-order model, though I also
      present evidence that some transition probabilities are conditioned on up to
      three preceding phrases. In addition, sequences were shown to be predictable with
      more than 54% accuracy overall, and predictability was positively correlated with
      the rate of song delivery. An assessment of the time homogeneity of syntax showed
      that transition probabilities between phrase types are largely stable over time,
      but that there was some evidence for modest changes in syntax within and between
      breeding seasons, a finding that I interpret to represent changes in breeding
      stage and social context rather than irreversible, secular shifts in syntax over
      time. These findings constitute a valuable addition to our understanding of bird
      song syntax in free-living birds, and will contribute to future attempts to
      understand the evolutionary importance of bird song syntax in avian
      communication. 

PMID- 27050538
TI  - Three-Year Follow-up of the Prospective, Randomized, Controlled Trial of Coflex
      Interlaminar Stabilization vs Instrumented Fusion in Patients With Lumbar
      Stenosis.
AB  - BACKGROUND: Traditional surgical options for the treatment of symptomatic lumbar
      spinal stenosis include decompression alone vs decompression and fusion; both
      options have potential limitations. OBJECTIVE: To report the 36-month follow-up
      analysis of the coflex Interlaminar Stabilization (Paradigm Spine, LLC, New York,
      New York) after decompression, examined under a Food and Drug Administration
      investigational device exemption clinical trial, which is intended to provide
      stabilization after decompression while preserving normal segmental motion at the
      treated level. METHODS: The coflex trial was a prospective, randomized
      investigational device exemption study conducted at 21 clinical sites in the
      United States. Baseline and follow-up visits collected demographics, clinical,
      and radiographic status. The primary endpoint was a measure of composite clinical
      success 24 months postoperatively. For this current 36-month analysis, composite
      clinical success was calculated using analogous methods. RESULTS: Composite
      clinical success at 36 months was achieved by 62.2% among 196 coflex Interlaminar
      Stabilization patients and 48.9% among 94 fusion patients (difference = 13.3%,
      95% confidence interval, 1.1%-25.5%, P = .03). Bayesian posterior probabilities
      for noninferiority (margin = -10%) and superiority of cofle Interlaminar
      Stabilization vs fusion were >0.999 and 0.984, respectively. Substantial and
      comparable improvements were observed in both groups for patient-reported
      outcomes, although the percentage with a clinically significant improvement
      (>=15) in the Oswestry Disability Index seemed larger for the coflex Interlaminar
      Stabilization group relative to the fusion group (P = .008). Radiographic
      measurements maintained index level and adjacent level range of motion in coflex
      Interlaminar Stabilization patients, although range of motion at the level
      superior to fusion was significantly increased (P = .005). CONCLUSION: Coflex
      Interlaminar Stabilization for stenosis is proven to be effective and durable at
      improving overall composite clinical success without altering normal spinal
      kinematic motion at the index level of decompression or adjacent levels.
      ABBREVIATIONS: CCS, composite clinical successCEC, clinical events committeeFDA,
      Food and Drug AdministrationIDE, investigational device exemptionILS, Coflex
      Interlaminar StabilizationODI, Oswestry Disability IndexSF-12, Short-Form 12VAS,
      visual analogue scalesZCQ, Zurich Claudication Questionnaire.

PMID- 27050539
TI  - [Multiparametric US of the Testicles--Selected Cases].

PMID- 27050540
TI  - [Not Available].

PMID- 27050543
TI  - [Not Available].

PMID- 27050544
TI  - [Not Available].

PMID- 27050546
TI  - [Not Available].

PMID- 27050547
TI  - [Not Available].

PMID- 27050548
TI  - [Not Available].

PMID- 27050549
TI  - Comparison of Gender Differences in Intracerebral Hemorrhage in a Multi-Ethnic
      Asian Population.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) accounts for 10-15% of all first time
      strokes and with incidence twice as high in the Asian compared to Western
      population. This study aims to investigate gender differences in ICH patient
      outcomes in a multi-ethnic Asian population. METHOD: Data for 1,192 patients
      admitted for ICH were collected over a four-year period. Multivariate logistic
      regression was used to identify independent predictors and odds ratios were
      computed for 30-day mortality and Glasgow Outcome Scale (GOS) comparing males and
      females. RESULT: Males suffered ICH at a younger age than females (62.2 +/- 13.2
      years vs. 66.3 +/- 15.3 years; P<0.001). The occurrence of ICH was higher among
      males than females at all ages until 80 years old, beyond which the trend was
      reversed. Females exhibited increased severity on admission as measured by
      Glasgow Coma Scale compared to males (10.9 +/- 4.03 vs. 11.4 +/- 4.04; P =
      0.030). No difference was found in 30-day mortality between females and males (F:
      30.5% [155/508] vs. M: 27.0% [186/688]), with unadjusted and adjusted odds ratio
      (F/M) of 1.19 (P = 0.188) and 1.21 (P = 0.300). At discharge, there was a non
      statistically significant but potentially clinically relevant morbidity
      difference between the genders as measured by GOS (dichotomized GOS of 4-5: F:
      23.7% [119/503] vs. M: 28.7% [194/677]), with unadjusted and adjusted odds ratio
      (F/M) of 0.77 (P = 0.055) and 0.87 (P = 0.434). CONCLUSION: In our multi-ethnic
      Asian population, males developed ICH at a younger age and were more susceptible
      to ICH than women at all ages other than the beyond 80-year old age group. In
      contrast to the Western population, neurological status of female ICH patients at
      admission was poorer and their 30-day mortality was not reduced. Although the
      study was not powered to detect significance, female showed a trend toward worse
      30-day morbidity at discharge.

PMID- 27050550
TI  - Curating Employee Ethics: Self-Glory Amidst Slow Violence at The China Tobacco
      Museum.
AB  - Seen through the prism of public health, the cigarette industry is an apparatus
      of death. To those who run it, however, it is something more prosaic: a workplace
      comprised of people whose morale is to be shepherded. Provisioning employees of
      the cigarette industry with psychic scaffolding to carry out effective daily work
      is a prime purpose of the China Tobacco Museum. This multistoried exhibition
      space in Shanghai is a technology of self, offering a carefully curated history
      of cigarette production thematized around tropes such as employee exaltation.
      Designed to anchor and vitalize the ethical outlook of those working for the
      world's most prolific cigarette conglomerate, the museum is a striking
      illustration that industrial strongholds of 'slow violence' produce their own
      forms of self-care.

PMID- 27050551
TI  - An IRF5 Decoy Peptide Reduces Myocardial Inflammation and Fibrosis and Improves
      Endothelial Cell Function in Tight-Skin Mice.
AB  - Interferon regulatory factor 5 (IRF5) has been called a "master switch" for its
      ability to determine whether cells mount proinflammatory or anti-inflammatory
      responses. Accordingly, IRF5 should be an attractive target for therapeutic drug
      development. Here we report on the development of a novel decoy peptide inhibitor
      of IRF5 that decreases myocardial inflammation and improves vascular endothelial
      cell (EC) function in tight-skin (Tsk/+) mice. Biolayer interferometry studies
      showed the Kd of IRF5D for recombinant IRF5 to be 3.72 +/- 0.74x10-6M. Increasing
      concentrations of IRF5D (0-100 MUg/mL, 24h) had no significant effect on EC
      proliferation or apoptosis. Treatment of Tsk/+ mice with IRF5D (1mg/kg/d
      subcutaneously, 21d) reduced IRF5 and ICAM-1 expression and monocyte/macrophage
      and neutrophil counts in Tsk/+ hearts compared to expression in hearts from PBS
      treated Tsk/+ mice (p<0.05). EC-dependent vasodilatation of facialis arteries
      isolated from PBS-treated Tsk/+ mice was reduced (~15%). IRF5D treatments
      (1mg/kg/d, 21d) improved vasodilatation in arteries isolated from Tsk/+ mice
      nearly 3-fold (~45%, p<0.05), representing nearly 83% of the vasodilatation in
      arteries isolated from C57Bl/6J mice (~55%). IRF5D (50MUg/mL, 24h) reduced
      nuclear translocation of IRF5 in myocytes cultured on both Tsk/+ cardiac matrix
      and C57Bl/6J cardiac matrix (p<0.05). These data suggest that IRF5 plays a causal
      role in inflammation, fibrosis and impaired vascular EC function in Tsk/+ mice
      and that treatment with IRF5D effectively counters IRF5-dependent mechanisms of
      inflammation and fibrosis in the myocardium in these mice. 

PMID- 27050552
TI  - Bioresorbable vascular scaffolds in clinical practice: state-of-the-art.
AB  - Coronary bioresorbable vascular scaffolds (BVS) are a new appealing therapeutic
      option in interventional cardiology. To date, the Absorb BVSTM (Abbott Vascular,
      Santa Clara, CA, USA) is the most used and studied device. Its backbone is made
      of poly-L-lactide and coated by a thin layer of poly-D,L-lactide; everolimus is
      released and the scaffold is fully degraded to H2O and CO2 in 2-3 years. The BVS
      technology seems to offer several theoretical advantages over metallic stent
      implantation. It gives temporary mechanical support to vessel wall, without
      permanently caging it. Hence, long-term endothelial function may be restored and
      natural vasomotion in response to external stimuli may be recovered. Finally, an
      eventual future surgical revascularization is not conditioned. Several
      observational and randomized trials assessing the performance and clinical
      outcomes of BVS have been recently published. The main aim of this review is to
      carry out a systematic analysis and to evaluate long-term efficacy and safety of
      the Absorb BVSTM. 

PMID- 27050554
TI  - Is native tissue always better?

PMID- 27050553
TI  - Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using
      CD14-ML Technology.
AB  - We previously reported a method to expand human monocytes through lentivirus
      mediated introduction of cMYC and BMI1, and we named the monocyte-derived
      proliferating cells, CD14-ML. CD14-ML differentiated into functional DC (CD14-ML
      DC) upon addition of IL-4, resulting in the generation of a large number of DC.
      One drawback of this method was the extensive donor-dependent variation in
      proliferation efficiency. In the current study, we found that introduction of
      BCL2 or LYL1 along with cMYC and BMI1 was beneficial. Using the improved method,
      we obtained CD14-ML from all samples, regardless of whether the donors were
      healthy individuals or cancer patients. In vitro stimulation of peripheral blood
      T cells with CD14-ML-DC that were loaded with cancer antigen-derived peptides led
      to the establishment of CD4+ and CD8+ T cell lines that recognized the peptides.
      Since CD14-ML was propagated for more than 1 month, we could readily conduct
      genetic modification experiments. To generate CD14-ML-DC that expressed antigenic
      proteins, we introduced lentiviral antigen-expression vectors and subjected the
      cells to 2 weeks of culture for drug-selection and expansion. The resulting
      antigen-expressing CD14-ML-DC successfully induced CD8+ T cell lines that were
      reactive to CMVpp65 or MART1/MelanA, suggesting an application in vaccination
      therapy. Thus, this improved method enables the generation of a sufficient number
      of DC for vaccination therapy from a small amount of peripheral blood from cancer
      patients. Information on T cell epitopes is not necessary in vaccination with
      cancer antigen-expressing CD14-ML-DC; therefore, all patients, irrespective of
      HLA type, will benefit from anti-cancer therapy based on this technology. 

PMID- 27050555
TI  - Pulmonary metastasectomy for suspected pancreaticobiliary cancer.
AB  - PURPOSE: Occasionally, pancreaticobiliary cancer presents as a relatively
      indolent disease and localized blood-borne lung metastases may be resectable. We
      reviewed our experience with therapeutic lung resections in pancreatic cancer
      patients. METHODS: In a retrospective cohort study of pancreatic cancer patients
      who underwent subsequent therapeutic lung resections, from 1996 to 2015, all
      clinical data were gathered for comparison between patients undergoing pancreatic
      pulmonary metastasectomy and those undergoing lung resection for other diseases.
      RESULTS: Among 29 patients with definitively treated pancreaticobiliary cancer
      who underwent lung resections with curative intent, 16 patients (55%) had
      resection of isolated pancreaticobiliary cancer metastases (group A) and 13
      patients (45%) had 15 resections of primary lung cancers, and one granuloma
      (group B). No surgical complications or operative mortalities occurred. The
      median disease-free interval (DFI) from definitive pancreatic cancer treatment to
      pulmonary metastasectomy or other nonmetastasectomy therapeutic lung resection
      was 24.0 and 8.0 months, respectively. The estimated median overall survival
      after lung resection was 33 months for all patients (95% confidence interval: 0,
      67) and 28 months for the group A pulmonary metastasectomy patients (95%
      confidence interval: 16, 40), corresponding to an estimated 5-year survival rate
      of 47% and 37%, respectively. Serum CA 19-9 level before lung resection
      significantly predicted mortality: adjusted hazard ratio 1.38 (95% confidence
      interval: 1.09, 1.74) per each 100-unit increment, P = .006. CONCLUSIONS:
      Although pancreaticobiliary cancers have an overall dismal prognosis, we
      recommend pulmonary metastasectomy in highly selected patients. Additionally, not
      all new lung masses in pancreatic cancer patients are metastases, and resection
      should be considered, for a second primary lung cancer is often found.

PMID- 27050556
TI  - Does Circulating Antibody Play a Role in the Protection of Piglets against
      Porcine Epidemic Diarrhea Virus?
AB  - The contribution of circulating antibody to the protection of naive piglets
      against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive
      antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to
      one of 6 different treatments using a randomized block design which provided for
      allocation of all treatments to all sows' litters. Each treatment was designed to
      achieve a different level of circulating anti-PEDV antibody via intraperitoneally
      administration of concentrated serum antibody. Piglets were orally inoculated
      with PEDV (USA/IN/2013/19338E, 1 x 103 TCID50 per piglet) 24 hours later and then
      monitored for 14 days. Piglets remained with their dam throughout the experiment.
      Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body
      weight, and body temperature were collected daily. Fecal samples were tested by
      PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested
      for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for
      the effects of systemic PEDV antibody levels on growth, body temperature, fecal
      shedding, survival, and antibody response. The analysis showed that circulating
      antibody partially ameliorated the effect of PEDV infection. Specifically,
      antibody-positive groups returned to normal body temperature faster and
      demonstrated a higher rate of survivability than piglets without PEDV antibody.
      When combined with previous literature on PEDV, it can be concluded that both
      systemic antibodies and maternal secretory IgA in milk contribute to the
      protection of the neonatal pig against PEDV infections. Overall, the results of
      this experiment suggested that passively administered circulating antibodies
      contributed to the protection of neonatal piglets against PEDV infection. 

PMID- 27050557
TI  - Intramuscular psoas lengthening during single-event multi-level surgery fails to
      improve hip dynamics in children with spastic diplegia. Clinical and kinematic
      outcomes in the short- and medium-terms.
AB  - BACKGROUND: In children with spastic diplegia, hip extension in terminal stance
      is limited by retraction of the psoas muscle, which decreases stride propulsion
      and step length on the contralateral side. Whether intramuscular psoas
      lengthening (IMPL) is effective remains controversial. The objective of this
      study was to assess the impact of IMPL as a component of single-event multi-level
      surgery (SEMLS) on spatial and temporal gait parameters, clinical hip flexion
      deformity, and hip flexion kinematics. HYPOTHESIS: IMPL as part of SEMLS does not
      significantly improve hip flexion kinematics. MATERIALS AND METHODS: A
      retrospective review was conducted of the medical charts of consecutive
      ambulatory children with cerebral palsy who had clinical hip flexion deformity
      (>10 degrees ) with more than 10 degrees  of excess hip flexion in terminal
      stance and who underwent SEMLS. The groups with and without IMPL were compared.
      Preoperative values of the clinical hip flexion contracture, hip flexion
      kinematics in terminal stance, and spatial and temporal gait parameters were
      compared to the values recorded after a mean postoperative follow-up of 2.4+/-2.0
      years (range, 1.0-8.7 years). Follow-up was longer than 3 years in 6 patients.
      RESULTS: Of 47 lower limbs (in 34 patients) included in the analysis, 15 were
      managed with IMPL. There were no significant between-group differences at
      baseline. Surgery was followed in all limbs by significant decreases in kinematic
      hip flexion and in the Gillette Gait Index. In the IMPL group, significant
      improvements occurred in clinical hip flexion deformity, walking speed, and step
      length. The improvement in kinematic hip extension was not significantly
      different between the two groups. Crouch gait recurred in 3 (8%) patients.
      DISCUSSION: The improvement in kinematic hip extension in terminal stance was not
      significantly influenced by IMPL but was, instead, chiefly dependent on improved
      knee extension and on the position of the ground reaction vector after SEMLS.
      IMPL remains indicated only when the clinical hip flexion deformity exceeds 20
      degrees . LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 27050558
TI  - An animal model of detrusor overactivity induced by depression.
AB  - INTRODUCTION: Depression is frequently found in patients suffering from
      overactive bladder. The aim of the study was to verify whether the 13-cis
      retinoic acid, a synthetic retinoid used in the treatment of acne, which was
      proven to induce depressive changes in both humans and animals, can cause
      detrusor overactivity symptoms in conscious rats. METHODS: In order to assess the
      13-cis-retinoic acid impact on the behavioural parameters, after 6weeks of
      intraperitoneal administration of retinoid in a dose of 1mg/kg/day, a forced swim
      test and cystometry were performed, and the locomotor activity of animals was
      assessed. The control group received a mixture of DMSO and physiological saline
      at a 1:1 ratio. RESULTS: 13-cis-retinoic acid caused cystometric parameter
      changes analogous to those observed in people with a urodynamic diagnosis of
      detrusor overactivity. The retinoid caused also an extension of the immobility
      time in the forced swim test which is consistent with increased depression
      related behaviour, with no impact on the locomotor activity of rats. The
      intravenous administration of solifenacin succinate in a single dose of 0.03mg/kg
      turned out to reverse changes in the cystometric parameters modified by 13-cis
      retinoic acid treatment. The histopathological analysis of bladders did not show
      any lesions in the upper layer of the umbrella cells, urothelium or muscles. The
      retinoid concentration level achieved in the animals tested turned out to be
      identical to that occurring in humans. DISCUSSION: 13-cis-retinoic acid can
      induce detrusor overactivity symptoms that are reversed by solifenacin succinate.

PMID- 27050559
TI  - Evaluation of a method utilizing PhysioFlow(r), a novel signal morphology-based
      form of impedance cardiography, to measure cardiac output in the conscious
      beagle.
AB  - INTRODUCTION: Currently, standard methods for measuring cardiac output are either
      invasive (i.e. flow probe) or are limited in terms of short measurement intervals
      and measurement variability (i.e. echocardiography). The ability to reliably
      measure cardiac output in a non-invasive manner in large animals would provide a
      valuable tool to expand functional cardiovascular endpoints in preclinical safety
      studies. PhysioFlow(r) is a novel method that uses waveform analysis of an
      impedance signal to measure cardiac output non-invasively. Unlike cardiac
      impedance techniques in the past, PhysioFlow(r) is not dependant on thoracic
      structure or basal thoracic impedance (Z0) and therefore this methodology is
      transferrable from human to animal models. METHODS: Three tool compounds with
      known effects on cardiac output were administered to conscious beagle dogs to
      determine if the non-invasive PhysioFlow(r) system could detect the expected
      changes in stroke volume and cardiac output as determined by literature
      references using the current standard methodologies (e.g. aortic blood flow and
      thermodilution). RESULTS: The PhysioFlow(r) system was able to detect increases
      in cardiac output when dosed with 20MUg/kg of Dobutamine, a decrease in cardiac
      output when dosed with 0.1mg/kg of Acepromazine, and no significant change in
      cardiac output when dosed with 2mg/kg of Minoxidil. These results are within
      expected ranges based on published literature (Stepien et al., 1995; Taylor et
      al., 2007). DISCUSSION: PhysioFlow(r), a signal morphology-based impedance
      cardiography, can be utilized to reliably and non-invasively measure cardiac
      output in beagle dogs.

PMID- 27050560
TI  - Overexpression of interleukin-33 is associated with poor prognosis of patients
      with glioma.
AB  - Interleukin-33 (IL-33) has shown diagnostic and prognostic values in multiple
      human cancers. However, there is little knowledge on the role of IL-33 in human
      gliomas and its association with disease prognosis. This study aimed to evaluate
      the value of IL-33 in the prognosis of glioma patients. The expression of IL-33
      was determined and compared in surgical specimens from 86 glioma patients and 16
      normal brain tissues. The associations of IL-33 expression with the
      clinicopathological features and prognosis of glioma patients were assessed. qRT
      PCR assay showed higher IL-33 mRNA expression in glioma tissues than in normal
      brain tissue ( p < 0.001), and significantly higher IL-33 mRNA expression was
      detected in both low- and high-grade glioma tissues relative to normal brain
      tissues ( p < 0.001). Western blotting revealed elevated IL-33 protein levels in
      glioma tissues compared to those in normal brain tissues, and immunohistochemical
      staining showed higher IL-33 protein expression in glioma tissues than in normal
      brain tissues. IL-33 expression correlated with the glioma grade ( p < 0.001) and
      Karnofsky performance status score ( p = 0.024), and the glioma patients with
      high IL-33 expression had a shorter progression-free survival ( p < 0.001) and
      overall survival ( p < 0.001) than those with low IL-33 expression. The
      univariate and multivariate analyses showed that IL-33 overexpression and the
      glioma grade were independent factors of a poor prognosis in glioma patients.
      Therefore, IL-33 may be a promising biomarker for the detection of gliomas, and
      IL-33 expression is useful for predicting the prognosis of the disease.

PMID- 27050561
TI  - Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South
      Africa Using Lot Quality Assurance Sampling.
AB  - BACKGROUND: KwaZulu-Natal (KZN) has the highest burden of notified multidrug
      resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in
      South Africa. A better understanding of spatial heterogeneity in the risk of drug
      resistance may help to prioritize local responses. METHODS: Between July 2012 and
      June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to
      classify the burden of rifampicin (RIF)-resistant TB among incident TB cases
      notified within the catchment areas of seven laboratories in two northern and one
      southern district of KZN. Decision rules for classification of areas as having
      either a high- or low-risk of RIF resistant TB (based on proportion of RIF
      resistance among all TB cases) were based on consultation with local policy
      makers. RESULTS: We classified five areas as high-risk and two as low-risk. High
      risk areas were identified in both Southern and Northern districts, with the
      greatest proportion of RIF resistance observed in the northernmost area, the
      Manguzi community situated on the Mozambique border. CONCLUSION: Our study
      revealed heterogeneity in the risk of RIF resistant disease among incident TB
      cases in KZN. This study demonstrates the potential for LQAS to detect geographic
      heterogeneity in areas where access to drug susceptibility testing is limited.

PMID- 27050562
TI  - Positioning the Answerable Body in Research.
AB  - This essay reflects upon my experiences as a field researcher participating with
      a running group organized to aid those without homes. Borrowing from dialogic as
      well as affect theory, I contemplate the importance of the answerable body in
      research by examining a series of defining moments during my experiences in the
      field. I conclude with a discussion of the theoretical and methodological
      implications surrounding the answerable body.

PMID- 27050563
TI  - Diagnostic accuracy of anti-RA33 antibody for rheumatoid arthritis: systematic
      review and meta-analysis.
AB  - OBJECTIVES: The main purpose of this meta-analysis is to evaluate the diagnostic
      value of anti-RA33 antibody for rheumatoid arthritis. METHODS: In order to obtain
      eligible studies, a systematic literature search was performed on PubMed, Web of
      science, EBSCO, CNKI and CBM from January 2000 to September 2015. Quality
      Assessment of Diagnostic Accuracy Studies (QUADAS) was employed to assess the
      quality of the relevant studies. Meta-disc 1.4 and Stata 11.0 were adopted in
      this meta-analysis. RESULTS: After rigorous review, fifty studies were included
      in this study, which are all reliable to summarise the diagnostic value in this
      meta-analysis. The result of the analysis shows the pooled sensitivity is 0.33
      (95% confidence interval (CI): 0.31-0.34) and the specificity is 0.90 (95% CI:
      0.89-0.90), for the diagnosis of rheumatoid arthritis. Besides, the area under
      the summary ROC curve (AUC) is 0.6863. CONCLUSIONS: The current evidence suggests
      that anti-RA33 antibody has high diagnostic specificity value for rheumatoid
      arthritis, which may be useful for the disease diagnostic application. To verify
      this conclusion, more prospective research on the diagnostic value of anti-RA33
      antibody for rheumatoid arthritis are needed in the future.

PMID- 27050564
TI  - Determinants of emigration and their impact on survival during dispersal in fox
      and jackal populations.
AB  - Animals disperse in response to poor resource conditions as a strategy of
      escaping harsh competition and stress, but may also disperse under good resource
      conditions, as these provide better chances of surviving dispersal and gaining
      fitness benefits such as avoiding kin competition and inbreeding. Individual
      traits should mediate the effect of resources, yielding a complex condition
      dependent dispersal response. We investigated how experimental food reductions in
      a food-rich environment around poultry-growing villages interact with individual
      traits (age, gender, body-mass) in two sympatric canids, red foxes and golden
      jackals, to jointly affect emigration propensity and survival during dispersal.
      Sub-adult foxes emigrated more frequently from the food-rich habitat than from
      the pristine, food-limited habitat, while adult foxes showed the opposite trend.
      During dispersal, adults exhibited lower survival while sub-adults did not
      experience additional mortality costs. Although fox mortality rates increased in
      response to food reduction, dispersal remained unchanged, while jackals showed
      strong dispersal response in two of the three repetitions. Jackal survival under
      food reduction was lowest for the dispersing individuals. While resources are an
      important dispersal determinant, different age classes and species experience the
      same resource environment differently and consequently have different
      motivations, yielding different dispersal responses and consequences. 

PMID- 27050565
TI  - Unravelling the Molecular Origin of the Regiospecificity in Extradiol Catechol
      Dioxygenases.
AB  - Many factors have been suggested to control the selectivity for extradiol or
      intradiol cleavage in catechol dioxygenases. The varied selectivity of model
      complexes and the ability to force an extradiol enzyme to do intradiol cleavage
      indicate that the problem may be complex. In this paper we focus on the
      regiospecificity of the proximal extradiol dioxygenase, homoprotocatechuate 2,3
      dioxygenase (HPCD), for which considerable advances have been made in our
      understanding of the mechanism from an experimental and computational standpoint.
      Two key steps in the reaction mechanism were investigated: (1) attack of the
      substrate by the superoxide moiety and (2) attack of the substrate by the oxyl
      radical generated by O-O bond cleavage. The selectivity at both steps was
      investigated through a systematic study of the role of the substrate and the
      first and second coordination spheres. For the isolated native substrate,
      intradiol cleavage is calculated to be both kinetically and thermodynamically
      favored, therefore nature must use the enzyme environment to reverse this
      preference. Two second sphere residues were found to play key roles in
      controlling the regiospecificity of the reaction: Tyr257 and His200. Tyr257
      controls the selectivity by modulating the electronic structure of the substrate,
      while His200 controls selectivity through steric effects and by preventing
      alternative pathways to intradiol cleavage. 

PMID- 27050566
TI  - Efficacy of a Guideline-Recommended Risk-Reduction Program to Improve
      Cardiovascular and Limb Outcomes in Patients With Peripheral Arterial Disease.
AB  - IMPORTANCE: Patients with peripheral arterial disease (PAD) are at a high risk
      for cardiovascular events, yet, to our knowledge, no studies have examined the
      effect of a comprehensive risk-reduction program on long-term outcomes for
      patients with PAD. OBJECTIVE: To investigative whether a program that focuses on
      8 major guideline-recommended risk-management therapies reduces cardiovascular
      and limb events in patients with PAD. DESIGN, SETTING AND PARTICIPANTS: An
      observational cohort study with up to 7 years of follow-up was conducted using
      data from administrative databases from Ontario, Canada, between July 1, 2004,
      and March 31, 2013. Patients with symptomatic PAD who were enrolled in the
      Systematic Assessment of Vascular Risk (SAVR) program at a single tertiary
      vascular center in Ontario between July 2004 and April 2007 were matched with up
      to 2 (control) patients with PAD from other Ontario tertiary vascular centers not
      enrolled in the program using propensity score methods. Cox proportional hazards
      regression analysis was used to compare outcomes. EXPOSURES: Program that
      promoted antiplatelet agents, statins, angiotensin-converting enzyme inhibitors,
      blood pressure control, lipid control, diabetic glycemic control, smoking
      cessation, and target body mass index by engaging vascular surgeons, family
      physicians, and patients with PAD. MAIN OUTCOMES AND MEASURES: The primary
      outcome was a composite risk ratio of death, acute myocardial infarction, or
      ischemic stroke. Secondary outcomes included rates of lower limb amputations,
      bypass surgical procedures, and peripheral angioplasties with and without a
      stent. RESULTS: A total of 791 patients were studied after propensity score
      matching; the mean (SD) age of patients in the SAVR group (n = 290) was 67.9
      (10.4) years and 68.2 (11.2) years in the control group (n = 501). During follow
      up, the SAVR group experienced the primary outcome at a significantly lower rate
      than the control group (adjusted hazard ratio [HR], 0.63; 95% CI, 0.52-0.77).
      Patients in the SAVR group were also less likely to have major amputation
      (adjusted HR, 0.47; 95% CI, 0.29-0.77), minor amputation (adjusted HR, 0.26; 95%
      CI, 0.13-0.54), bypass surgery (adjusted HR, 0.47; 95% CI, 0.30-0.73), or
      hospitalization due to heart failure (adjusted HR, 0.73; 95% CI, 0.53-1.00). The
      rate of peripheral angioplasty with or without a stent was higher among the SAVR
      group (adjusted HR, 2.97; 95% CI, 2.15-4.10). CONCLUSIONS AND RELEVANCE: A
      guideline-recommended risk-reduction program targeted at patients with PAD was
      associated with fewer cardiovascular and limb events over the long-term. This
      finding emphasizes the need for well-designed prospective studies to develop and
      examine the effect of such programs on reducing PAD-related morbidity, mortality,
      and health care costs.

PMID- 27050567
TI  - Molecular Mapping of Stripe Rust Resistance Gene Yr76 in Winter Club Wheat
      Cultivar Tyee.
AB  - Tyee, one of the wheat cultivars used to differentiate races of Puccinia
      striiformis f. sp. tritici in the United States, was identified to have a single
      gene for all-stage resistance, tentatively named YrTye. To map the gene, Tyee was
      crossed with 'Avocet Susceptible' (AvS). Genetic analysis of the F1, F2, F2:3,
      and BC1 progenies confirmed a single dominant gene for resistance to race PSTv-37
      that is avirulent to YrTye. A mapping population of 135 F2 plants was phenotyped
      with PSTv-37 and the derived F2:3 lines were tested with races PSTv-37, PSTv-40,
      and PSTv-79. The F2 mapping population was genotyped with simple sequence repeat
      (SSR) markers. A genetic map comprising 13 SSR markers located YrTye in
      chromosome 3AS flanked distally by SSR marker wmc11 and proximally by wmc532 at
      2.6 and 3.4 cM, respectively. Amplification of Chinese Spring 3A deletion lines
      placed the gene in the distal bin 3AS4-0.45 to 1.00. Because YrTye is different
      from all formally named Yr genes in chromosomal location, we permanently name the
      gene Yr76. A near-isogenic line of spring common wheat was developed and selected
      by testing F3 lines derived from a AvS*4/Tyee cross with Tyee-avirulent and
      virulent races and the flanking markers. The specific SSR alleles flanking Yr76
      were validated using cultivars and breeding lines with and without the gene, and
      showed high polymorphisms. The specificity of Yr76 is useful in differentiating
      P. striiformis f. sp. tritici races, and its tightly linked markers will be
      useful in developing resistant cultivars when combining the gene with other genes
      for resistance to stripe rust.

PMID- 27050568
TI  - The Age of Effectors: Genome-Based Discovery and Applications.
AB  - Microbial pathogens cause devastating diseases on economically and ecologically
      important plant species, threatening global food security, and causing billions
      of dollars of losses annually. During the infection process, pathogens secrete so
      called effectors that support host colonization, often by deregulating host
      immune responses. Over the last decades, much of the research on molecular plant
      microbe interactions has focused on the identification and functional
      characterization of such effectors. The increasing availability of sequenced
      plant pathogen genomes has enabled genomics-based discovery of effector
      candidates. Nevertheless, identification of full plant pathogen effector
      repertoires is often hampered by erroneous gene annotation and the localization
      effector genes in genomic regions that are notoriously difficult to assemble.
      Here, we argue that recent advances in genome sequencing technologies, genome
      assembly, gene annotation, as well as effector identification methods hold
      promise to disclose complete and correct effector repertoires. This allows to
      exploit complete effector repertoires, and knowledge of their diversity within
      pathogen populations, to develop durable and sustainable resistance breeding
      strategies, disease control, and management of plant pathogens.

PMID- 27050569
TI  - Clonal Expansion and Migration of a Highly Virulent, Defoliating Lineage of
      Verticillium dahliae.
AB  - We used a population genomics approach to test the hypothesis of clonal expansion
      of a highly fit genotype in populations of Verticillium dahliae. This fungal
      pathogen has a broad host range and can be dispersed in contaminated seed or
      other plant material. It has a highly clonal population structure, with several
      lineages having nearly worldwide distributions in agricultural crops. Isolates in
      lineage 1A are highly virulent and cause defoliation in cotton, okra, and olive
      (denoted 1A/D), whereas those in other lineages cause wilting but not defoliation
      (ND). We tested whether the highly virulent lineage 1A/D could have spread from
      the southwestern United States to the Mediterranean basin, as predicted from
      historical records. We found 187 single-nucleotide polymorphisms (SNPs),
      determined by genotyping by sequencing, among 91 isolates of lineage 1A/D and 5
      isolates in the closely related lineage 1B/ND. Neighbor-joining and maximum
      likelihood analyses on the 187 SNPs showed a clear divergence between 1A/D and
      1B/ND haplotypes. Data for only 77 SNPs were obtained for all 96 isolates (no
      missing data); lineages 1A/D and 1B/ND differed by 27 of these 77 SNPs,
      confirming a clear divergence between the two lineages. No evidence of
      recombination was detected within or between these two lineages. Phylogenetic and
      genealogical analyses resulted in five distinct subclades of 1A/D isolates that
      correlated closely with geographic origins in the Mediterranean basin, consistent
      with the hypothesis that the D pathotype was introduced at least five times in
      independent founder events into this region from a relatively diverse source
      population. The inferred ancestral haplotype was found in two isolates sampled
      before 1983 from the southwestern United States, which is consistent with
      historical records that 1A/D originated in North America. The five subclades
      coalesce with the ancestral haplotype at the same time, consistent with a
      hypothesis of rapid population expansion in the source population during the
      emergence of 1A/D as a severe pathogen of cotton in the United States.

PMID- 27050570
TI  - Etiology and Epidemiological Conditions Promoting Fusarium Root Rot in
      Sweetpotato.
AB  - Sweetpotato production in the United States is limited by several postharvest
      diseases, and one of the most common is Fusarium root rot. Although Fusarium
      solani is believed to be the primary causal agent of disease, numerous other
      Fusarium spp. have been reported to infect sweetpotato. However, the diversity of
      Fusarium spp. infecting sweetpotato in North Carolina is unknown. In addition,
      the lack of labeled and effective fungicides for control of Fusarium root rot in
      sweetpotato creates the need for integrated strategies to control disease.
      Nonetheless, epidemiological factors that promote Fusarium root rot in
      sweetpotato remain unexplored. A survey of Fusarium spp. infecting sweetpotato in
      North Carolina identified six species contributing to disease, with F. solani as
      the primary causal agent. The effects of storage temperature (13, 18, 23, 29, and
      35 degrees C), relative humidity (80, 90, and 100%), and initial inoculum level
      (3-, 5-, and 7-mm-diameter mycelia plug) were examined for progression of
      Fusarium root rot caused by F. solani and F. proliferatum on 'Covington'
      sweetpotato. Fusarium root rot was significantly reduced (P < 0.05) at lower
      temperatures (13 degrees C), low relative humidity levels (80%), and low initial
      inoculum levels for both pathogens. Sporulation of F. proliferatum was also
      reduced under the same conditions. Qualitative mycotoxin analysis of roots
      infected with one of five Fusarium spp. revealed the production of fumonisin B1
      by F. proliferatum when infecting sweetpotato. This study is a step toward
      characterizing the etiology and epidemiology of Fusarium root rot in sweetpotato,
      which allows for improved disease management recommendations to limit postharvest
      losses to this disease. 

PMID- 27050571
TI  - Distribution of 'Candidatus Liberibacter asiaticus' Above and Below Ground in
      Texas Citrus.
AB  - Detection of 'Candidatus Liberibacter asiaticus' represents one of the most
      difficult, yet critical, steps of controlling Huanglongbing disease. Efficient
      detection relies on understanding the underlying distribution of bacteria within
      trees. To that end, we studied the distribution of 'Ca. L. asiaticus' in leaves
      of 'Rio Red' grapefruit trees and in roots of 'Valencia' sweet orange trees
      grafted onto sour orange rootstock. We performed two sets of leaf collection on
      grapefruit trees; the first a selective sampling targeting symptomatic leaves and
      their neighbors and the second a systematic collection disregarding symptomology.
      From uprooted orange trees, we exhaustively sampled fibrous roots. In this study,
      the presence of 'Ca. L. asiaticus' was detected in leaves using real-time
      polymerase chain reaction (PCR) targeting the 16S ribosomal gene and in roots
      using the rpIJ/rpIL ribosomal protein genes and was confirmed with conventional
      PCR and sequencing of the rpIJ/rpIL gene in both tissues. Among randomly
      collected leaves, 'Ca. L. asiaticus' was distributed in a patchy fashion.
      Detection of 'Ca. L. asiaticus' varied with leaf symptomology with symptomatic
      leaves showing the highest frequency (74%) followed by their neighboring
      asymptomatic leaves (30%), while randomly distributed asymptomatic leaves had the
      lowest frequency (20%). Among symptomatic leaves, we found statistically
      significant differences in mean number of bacterial cells with respect to both
      increasing distance of the leaf from the trunk and cardinal direction. The titer
      of 'Ca. L. asiaticus' cells was significantly greater on the north side of trees
      than on the south and west sides. Moreover, these directions showed different
      spatial distributions of 'Ca. L. asiaticus' with higher titers near the trunk on
      the south and west sides as opposed to further from the trunk on the north side.
      Similarly, we found spatial variation in 'Ca. L. asiaticus' distribution among
      root samples. 'Ca. L. asiaticus' was detected more frequently and bacterial
      abundances were higher among horizontally growing roots just under the soil
      surface (96%) than among deeper vertically growing roots (78%). Bacterial
      abundance declined slightly with distance from the trunk. These results point to
      paths of research that will likely prove useful to combating this devastating
      disease. 

PMID- 27050572
TI  - Rice Bran Amendment Suppresses Potato Common Scab by Increasing Antagonistic
      Bacterial Community Levels in the Rhizosphere.
AB  - Potato common scab (PCS), caused by pathogenic Streptomyces spp., is a serious
      disease in potato production worldwide. Cultural practices, such as optimizing
      the soil pH and irrigation, are recommended but it is often difficult to
      establish stable disease reductions using these methods. Traditionally, local
      farmers in southwest Japan have amended soils with rice bran (RB) to suppress
      PCS. However, the scientific mechanism underlying disease suppression by RB has
      not been elucidated. The present study showed that RB amendment reduced PCS by
      repressing the pathogenic Streptomyces population in young tubers. Amplicon
      sequencing analyses of 16S ribosomal RNA genes from the rhizosphere microbiome
      revealed that RB amendment dramatically changed bacterial composition and led to
      an increase in the relative abundance of gram-positive bacteria such as
      Streptomyces spp., and this was negatively correlated with PCS disease severity.
      Most actinomycete isolates derived from the RB-amended soil showed antagonistic
      activity against pathogenic Streptomyces scabiei and S. turgidiscabies on R2A
      medium. Some of the Streptomyces isolates suppressed PCS when they were
      inoculated onto potato plants in a field experiment. These results suggest that
      RB amendment increases the levels of antagonistic bacteria against PCS pathogens
      in the potato rhizosphere. 

PMID- 27050573
TI  - Susceptibility of Maize to Stalk Rot Caused by Fusarium graminearum
      Deoxynivalenol and Zearalenone Mutants.
AB  - Fusarium graminearum is a destructive pathogen of cereals that can cause stalk
      rot in maize. Stalk rot results in yield losses due to impaired grain filling,
      premature senescence, and lodging, which limits production and harvesting of
      ears. In addition, mycotoxins can make infected tissues unfit for silage. Our
      objectives were to evaluate the natural variation in stalk rot resistance among
      maize inbreds, to establish whether deoxynivalenol (DON)- and zearalenone (ZEA)
      deficient strains are pathogenic on a panel of diverse inbreds, and to quantify
      the accumulation of DON in infected stalk tissue. Wild-type F. graminearum and
      mycotoxin mutants (DON and ZEA) were used to separately inoculate stalks of 9
      week-old plants of 20 inbreds in the greenhouse. Plants were evaluated for lesion
      area at the inoculation point at 0, 2, 14, and 28 days postinoculation and
      tissues around lesions were sampled to determine the DON content. Regardless of
      their ability to produce DON or ZEA, all tested F. graminearum strains caused
      stalk rot; however, significant differences in disease levels were detected.
      Among the tested inbreds, Mp717 was resistant to all three F. graminearum strains
      while Mp317 and HP301 were only partially resistant. Accumulation of DON was
      significantly lower in infected stalks of the resistant and partially resistant
      inbreds than the susceptible inbreds. Analysis of the 20 inbreds using data from
      17 simple-sequence repeats revealed population structure among the individuals;
      however, there was no association between genetic clustering and stalk rot
      resistance. These findings are an additional step toward breeding maize inbreds
      suitable for planting in fields infested with F. graminearum. 

PMID- 27050574
TI  - An Improved Method for Measuring Quantitative Resistance to the Wheat Pathogen
      Zymoseptoria tritici Using High-Throughput Automated Image Analysis.
AB  - Zymoseptoria tritici causes Septoria tritici blotch (STB) on wheat. An improved
      method of quantifying STB symptoms was developed based on automated analysis of
      diseased leaf images made using a flatbed scanner. Naturally infected leaves (n =
      949) sampled from fungicide-treated field plots comprising 39 wheat cultivars
      grown in Switzerland and 9 recombinant inbred lines (RIL) grown in Oregon were
      included in these analyses. Measures of quantitative resistance were percent leaf
      area covered by lesions, pycnidia size and gray value, and pycnidia density per
      leaf and lesion. These measures were obtained automatically with a batch
      processing macro utilizing the image-processing software ImageJ. All phenotypes
      in both locations showed a continuous distribution, as expected for a
      quantitative trait. The trait distributions at both sites were largely
      overlapping even though the field and host environments were quite different.
      Cultivars and RILs could be assigned to two or more statistically different
      groups for each measured phenotype. Traditional visual assessments of field
      resistance were highly correlated with quantitative resistance measures based on
      image analysis for the Oregon RILs. These results show that automated image
      analysis provides a promising tool for assessing quantitative resistance to Z.
      tritici under field conditions. 

PMID- 27050575
TI  - Spatial Genetic Structure and Population Dynamics of Gummy Stem Blight Fungi
      Within and Among Watermelon Fields in the Southeastern United States.
AB  - The epidemiology of gummy stem blight (GSB) of cucurbits, particularly the
      sources of inoculum for epidemics, and the regional population genetic structure
      of the causal fungi Stagonosporopsis cucurbitacearum (syn. Didymella bryoniae),
      S. citrulli, and S. caricae are not well understood. Our goal was to better
      understand the population structure and fine-scale spatial genetic structure of
      Stagonosporopsis spp. in the southeastern United States. Overall, 528 isolates
      collected from nine fields in 2012, 2013, and 2014 were genotyped with 16
      microsatellite markers. In 2013, S. caricae was first detected in the
      southeastern United States; however, S. citrulli remained the dominant species,
      representing 96.4% of the isolates. Principal coordinates analysis, discriminant
      analysis of principle components, and analysis of molecular variance indicated
      that most populations of S. citrulli were genotypically diverse, yet dominated by
      widely distributed clones that contributed to regional population structure.
      Spatial genetic structure resulting from aggregation of clonal genotypes at
      distances of less than 10 meters was detected within two of three fields in which
      isolate location was recorded. Studies on the epidemiological and fitness
      differences between S. citrulli and S. caricae and of prevalent and widespread
      clones will provide insight into the population structure and species dynamics
      observed in GSB epidemics. 

PMID- 27050576
TI  - Prevalence, Development, and Significance of Ascochyta Blight Caused by
      Peyronellaea pinodes in Pisum elatius Populations Growing in Natural Ecosystems.
AB  - Wild Pisum populations prevail in Israel in regions with diverse climatic
      conditions. A comprehensive survey was conducted in the winters of 2007-08 and
      2008-09 at two sites in northern Israel, aiming to (i) document the density of
      Pisum elatius plants in natural ecosystems and elucidate factors related to their
      initial infection by Ascochyta blight and (ii) determine the factors governing
      disease development over time on individual plants. The surveyors identified P.
      elatius plants growing in designated quadrats, inspected each plant visually, and
      recorded the incidence and severity of its Ascochyta blight symptoms. Ascochyta
      blight, caused by Peyronellaea pinodes, was ubiquitous in Pisum elatius
      populations at both survey sites in both seasons. However, the total leaf area
      exhibiting disease symptoms of individual plants was very low, and stem and pod
      infections were rarely observed. Based on analyses of the survey data, it was
      suggested that, in natural ecosystems, the teleomorph stage of Peyronellaea
      pinodes serves as the main source of the primary and the secondary inoculum of
      the disease. In addition, it was found that infected leaves dropped off soon
      after infection, thereby precluding development of stem lesions. The plants
      continued growing and did not die; thus, they overcame the disease and could be
      considered "cured". This phenomenon was examined and confirmed in artificially
      inoculated, potted-plant experiments. It would be worthwhile to exploit the
      potential of this unique resistance mechanism as a tool for Ascochyta blight
      management in pea breeding. 

PMID- 27050577
TI  - Identification of a Pi9-Containing Rice Germplasm with a Newly Developed Robust
      Marker.
AB  - The Pi9 gene in rice, originating from Oryza minuta, is an effective resistance
      gene for controlling rice blast disease. However, currently available linked DNA
      markers do not accurately identify the function of Pi9, thus hindering its
      efficient incorporation into new cultivars through marker-assisted selection
      (MAS). In addition, no known Pi9-containing rice germplasm is available to
      breeders. In the present study, DNA sequence variation of Pi9 alleles and their
      family members was analyzed in 40 diverse rice germplasm accessions from the AA
      genome to develop a robust Pi9 marker. In total, 29 DNA primers of 20 to 23
      nucleotides were designed and each possible combination of primer pairs was used
      to detect Pi9. Only one combination of DNA primers, KS28/KS6, was identified to
      specifically detect Pi9 in the monogenic line IRBL9-W. The presence of Pi9 was
      verified with the predicted Pi9-specific blast reaction. Subsequently, 201
      genetically diverse mini-core rice accessions from 114 countries were screened
      with KS28/KS6. One germplasm, IR 9660-48-1-1-2, was identified to carry Pi9 and
      the function of Pi9 was verified with pathogenicity assays. This robust Pi9
      marker and a rice germplasm, IR9660-48-1-1-2 (GSOR310687), carrying Pi9 can be
      used to improve blast resistance with a MAS approach. 

PMID- 27050578
TI  - The Temperature Response and Aggressiveness of Peyronellaea pinodes Isolates
      Originating from Wild and Domesticated Pisum sp. in Israel.
AB  - Domesticated pea fields are grown in relatively close proximity to wild pea
      species in Israel. Despite the major role attributed to ascochyta blight in
      causing yield losses in domesticated pea, very limited information is available
      on the pathogens prevailing in natural ecosystems. The objectives of this study
      were (i) to identify the species causing ascochyta blight symptoms on leaves,
      stems, and petioles of domesticated pea and wild Pisum plants in Israel, and (ii)
      to quantify the temperature response(s) and aggressiveness of such pathogens
      originating from Pisum plants growing in sympatric and allopatric contexts.
      Eighteen fungal isolates were examined and identified; three of them were sampled
      from Pisum sativum, 11 from Pisum fulvum, and four from Pisum elatius. All
      isolates were identified as Peyronellaea pinodes. Spore germination and mycelial
      growth took place over a wide range of temperatures, the lower and upper cardinal
      temperatures being 2 to 9 and 33 to 38 degrees C, respectively; the optimal
      temperatures ranged from 22 to 26 degrees C. At an optimal temperature, disease
      severity was significantly higher for plants maintained under moist conditions
      for 24 h postinoculation than for those exposed to humidity for 5 or 10 h.
      Analyses of the data revealed that temperature responses, spore germination
      rates, and aggressiveness of isolates sampled from domesticated pea plants did
      not differ from those of isolates sampled from adjacent or distant wild
      populations. Host specificity was not observed. These observations suggest that
      Israel may be inhabited by a single metapopulation of P. pinodes. 

PMID- 27050579
TI  - More options = more access.

PMID- 27050580
TI  - Tackling the brain: Clues emerge about the pathology of sports-related brain
      trauma.

PMID- 27050581
TI  - Mining for answers: Tuberculosis research informs class action sought by gold
      miners.

PMID- 27050582
TI  - Out with the bad: Studying autophagy to fight infectious disease.

PMID- 27050584
TI  - New company aims to broaden researchers' access to organoids.

PMID- 27050585
TI  - PTEN enables the development of pre-B acute lymphoblastic leukemia.

PMID- 27050586
TI  - A liquid biopsy for cancer immunotherapy.

PMID- 27050587
TI  - Burning fat fuels photoreceptors.

PMID- 27050588
TI  - Patient iPSCs: a new discovery tool for Smith-Lemli-Opitz syndrome.

PMID- 27050590
TI  - Corrigendum: Long-term glycemic control using polymer-encapsulated human stem
      cell-derived beta cells in immune-competent mice.

PMID- 27050591
TI  - Corrigendum: A SARS-like cluster of circulating bat coronaviruses shows potential
      for human emergence.

PMID- 27050592
TI  - Corrigendum: Myeloid-derived growth factor (C19orf10) mediates cardiac repair
      following myocardial infarction.

PMID- 27050589
TI  - Advancing the understanding of autism disease mechanisms through genetics.
AB  - Progress in understanding the genetic etiology of autism spectrum disorders (ASD)
      has fueled remarkable advances in our understanding of its potential
      neurobiological mechanisms. Yet, at the same time, these findings highlight
      extraordinary causal diversity and complexity at many levels ranging from
      molecules to circuits and emphasize the gaps in our current knowledge. Here we
      review current understanding of the genetic architecture of ASD and integrate
      genetic evidence, neuropathology and studies in model systems with how they
      inform mechanistic models of ASD pathophysiology. Despite the challenges, these
      advances provide a solid foundation for the development of rational, targeted
      molecular therapies. 

PMID- 27050593
TI  - Corrigendum: Multiphoton imaging reveals a new leukocyte recruitment paradigm in
      the glomerulus.

PMID- 27050594
TI  - Corrigendum: PAR1 signaling regulates the retention and recruitment of EPCR
      expressing bone marrow hematopoietic stem cells.

PMID- 27050595
TI  - Enzyme activity and microorganisms diversity in soil contaminated with the Boreal
      58 WG herbicide.
AB  - Next-generation herbicides are relatively safe when used properly, but the
      recommended rates are relatively low, which can lead to overdosing. This study
      evaluated the responses of soil-dwelling microorganisms and soil enzymes to
      contamination with the Boreal 58 WG herbicide. The analyzed product contains
      active ingredients flufenacet and isoxaflutole. All tests were performed under
      laboratory conditions. The analyzed material was sandy clay. Boreal 58 WG was
      introduced to soil in four doses. Soil without the addition of the herbicide
      served as the control. The soil was mixed with the tested herbicide, and its
      moisture content was maintained at 50% of capillary water capacity. Biochemical
      and microbiological analyses were performed on experimental days 0, 20, 40, 80
      and 160. Accidental contamination of soil with the Boreal 58 WG herbicide led to
      a relatively minor imbalance in the soil microbiological and biochemical profile.
      The herbicide dose influenced dehydrogenase activity in only 0.84%, urease
      activity in 2.04%, beta-glucosidase activity in 8.26%, catalase activity in
      12.40%, arylsulfatase activity in 12.54%, acid phosphatase activity in 42.11%,
      numbers of organotrophic bacteria in 18.29%, actinomyces counts in 1.31% and
      fungi counts in 6.86%. 

PMID- 27050596
TI  - Blood Transfusion Following Colorectal Resection: What Is the Real Story?

PMID- 27050597
TI  - Complete Pathological Response After Neoadjuvant Long-Course Chemoradiotherapy
      for Rectal Cancer and Its Relationship to the Degree of T3 Mesorectal Invasion.
AB  - BACKGROUND: Many studies have shown significantly improved outcomes (reduced
      local recurrence and improved overall survival) for patients achieving a complete
      pathological response from neoadjuvant chemoradiotherapy. OBJECTIVE: This study
      aimed to document the complete pathological response rate and outcomes in
      patients receiving preoperative long-course chemoradiotherapy stratified for the
      extent of T3 mesorectal invasion measured on preoperative imaging. DESIGN: This
      is a retrospective study of prospectively collected data, of patients with rectal
      cancer in the Cabrini Monash University Department of Surgery colorectal
      neoplasia database, incorporating data from Cabrini Hospital and The Alfred
      Hospital, identifying patients entered between January 2010 and June 2014.
      PATIENTS AND SETTINGS: One hundred eighteen patients with T3 rectal cancer met
      the selection criteria for the study; 26 achieved complete pathological response
      (22%). MAIN OUTCOME MEASURES: Outcomes in terms of complete pathological response
      and oncological outcomes such as disease-free and overall survival were analyzed.
      RESULTS: Patients with complete pathological response had significantly less
      preoperative invasion than those with no complete pathological response (p <
      0.001). Depth of invasion was the only variable associated with complete
      pathological response (p < 0.002), and the likelihood of complete pathological
      response decreased by 35% for every millimeter of invasion. Complete pathological
      response was associated with increased disease-free survival (p = 0.018) and a
      lower risk of cancer progression (p = 0.046). Depth of invasion was associated
      with an increased risk of death after surgery; HR increased by 1.07 (95% CI, 1.00
      1.15) for each 1-mm increase in invasion. LIMITATIONS: This was a retrospective
      study with the usual limitations, although these were minimized through the use
      of a clinician-driven prospective database. CONCLUSIONS: The smaller the degree
      of T3 invasion, the higher the chance of achieving complete pathological response
      (up to 35%), which is associated with improved disease-free and overall survival.
      A higher complete pathological response rate is observed in early T3 disease in
      comparison with more extensive T3 invasion.

PMID- 27050598
TI  - Persistent Asymptomatic Anastomotic Leakage After Laparoscopic Sphincter-Saving
      Surgery for Rectal Cancer: Can Diverting Stoma Be Reversed Safely at 6 Months?
AB  - BACKGROUND: Anastomotic leakage after rectal cancer surgery raises the problem of
      the timing of diverting stoma reversal. OBJECTIVE: The purpose of this study was
      to assess whether stoma reversal can be safely performed at 6 months after
      laparoscopic sphincter-saving surgery for rectal cancer with total mesorectal
      excision in patients with persistent asymptomatic anastomotic leakage. DESIGN:
      This was a retrospective analysis of a prospective database. SETTINGS: The study
      was conducted at a tertiary colorectal surgery referral center. PATIENTS: All of
      the patients with anastomotic leakage were treated conservatively after sphincter
      saving laparoscopic total mesorectal excision for rectal cancer. MAIN OUTCOME
      MEASURES: The main study measure was postoperative morbidity. RESULTS: A total of
      110 (26%) of 429 patients who presented with anastomotic leakage and were treated
      conservatively were diagnosed only on CT scan (60 symptomatic (14%) and 50
      asymptomatic (12%)). During follow up, 82 (75%) of 110 anastomotic leakages
      healed spontaneously after a mean delay of 16 +/- 6 weeks (range, 4-30 weeks).
      Among these patients, 7 (9%) of 82 developed postoperative symptomatic pelvic
      sepsis after stoma reversal. Among the 28 patients remaining, 3 died during
      follow-up. The remaining 25 patients (23%) presented with persistent asymptomatic
      anastomotic leakage with chronic sinus >6 months after rectal surgery. Stoma
      reversal was performed in 19 asymptomatic patients, but 3 (16%) of 19 developed
      postoperative symptomatic pelvic sepsis after stoma reversal (3/19 vs 7/82
      patients; p = 0.217), requiring a redo surgery with transanal colonic pull
      through and delayed coloanal anastomosis (n = 2) or standard coloanal anastomosis
      (n = 1). Regarding the 6 final patients, abdominal redo surgery was performed
      because of either symptoms or anastomotic leakage with a large presacral cavity.
      LIMITATIONS: This study was limited by its small sample size. CONCLUSIONS: In the
      great majority of patients with persistent anastomotic leakage at 6 months after
      total mesorectal excision, stoma reversal can be safely performed.

PMID- 27050599
TI  - Stage-Dependent Frequency of Lymph Node Metastases in Patients With Rectal
      Carcinoma After Preoperative Chemoradiation: Results from the CAO/ARO/AIO-94
      Trial and From a Comparative Prospective Evaluation With Extensive Pathological
      Workup.
AB  - BACKGROUND: For patients with ycT1/2 rectal carcinomas after neoadjuvant
      chemoradiotherapy, local excision instead of radical surgery has increasingly
      been discussed as a way to avoid postoperative morbidity associated with radical
      surgery. OBJECTIVE: The purpose of this study was to determine the incidence of
      lymph node metastases in total mesorectal excision specimens with ypT0, ypT1/2,
      and ypT3/4 rectal cancers. DESIGN: This is a prospective and retrospective cohort
      study. SETTINGS: This study was conducted in tertiary referral hospitals that are
      part of the German Rectal Cancer Study Group. PATIENTS: A total of 479 patients
      with stage II and III rectal cancers treated within phase III trials of the
      German Rectal Cancer Study Group were evaluated. Specimens from 81 patients
      treated in the Working Group of Surgical Oncology/Working Group of Radiation
      Oncology/Working Group of Medical Oncology of the Germany Cancer Society
      (CAO/ARO/AIO-04) trial were prospectively studied with extensive microscopic
      screening of the entire mesorectum. The frequency and localization of nodal
      metastases were specified and compared with those of 398 patients having received
      neoadjuvant chemoradiation within the CAO/ARO/AIO-94 trial. MAIN OUTCOME
      MEASURES: Frequency and localization of mesorectal lymph node metastases in
      patients with ypT0, ypT1/2, or ypT3/4 cancer were measured. RESULTS: A mean
      number of 28.0 +/- 13.7 nodes were detected per specimen within the prospective
      group. A total of 25% of patients in the ypT1/2 group had nodal metastases
      compared with 40% in the ypT3/4 group. Patients with node-positive ypT1/2 had a
      mean number of 2.2 metastases, and 55% of these metastases were located far from
      the primary lesion in the proximal mesorectum. Within the CAO/ARO/AIO-94 cohort
      (n = 398), 19% of patients with ypT1/2 (ypT1 = 22%; ypT2 = 18%) had ypN+ status
      compared with 43% with ypT3/4 cancers (ypT3 = 40%; ypT4 = 73%). LIMITATIONS: Low
      numbers of patients with ypT0 limited the evaluation of nodal metastases in
      pathologic complete responders. CONCLUSIONS: Even in good responders (ypT1/2),
      >20% of rectal carcinomas still harbored residual lymph node metastases. Local
      excision for patients with ycT1/2 rectal cancers would, thus, miss metastases in
      a considerable percentage and might involve the risk of significant
      undertreatment in a number of patients.

PMID- 27050600
TI  - Clinical Significance of International Union Against Cancer pN Staging and Lymph
      Node Ratio in Node-Positive Colorectal Cancer after Advanced Lymph Node
      Dissection.
AB  - BACKGROUND: Lymph node retrieval in colorectal cancer can be improved by using
      advanced histopathological techniques like methylene blue-assisted lymph node
      dissection, which results in a doubling or even tripling of the lymph node count
      in comparison with conventional lymph node dissection techniques. However, it is
      not clear whether the established lymph node staging systems are suitable for
      predicting patients' prognoses under these circumstances. OBJECTIVE: The aim of
      this study was to determine whether the current lymph node staging systems are
      suitable when advanced dissection methods are used. DESIGN: This is a
      retrospective cohort study. SETTING AND PATIENTS: We formed a study group
      (methylene blue-assisted lymph node dissection) of 293 patients and a control
      group (conventional lymph node dissection) of 232 patients, each with node
      positive cases. Conventional pN staging according to the International Union
      Against Cancer, seventh edition, and lymph node ratio were applied. MAIN OUTCOME
      MEASURES: Overall survival was compared by using the different staging systems in
      a uni- and multivariable fashion. RESULTS: The lymph node ratio values were
      reduced in the advanced methylene blue-assisted lymph node dissection group in
      comparison with the conventional lymph node dissection group (0.1 vs 0.3, p <
      0.001). Although pN staging proved to be reliable, the cutoff values for lymph
      node ratio staging had to be adapted. The new cutoffs (0.07, 0.15, and 0.34) were
      prognostic. However, multivariable analysis revealed pN staging and vascular
      invasion, but not lymph node ratio, as independently prognostic in the methylene
      blue-assisted lymph node dissection group. LIMITATIONS: The study group and
      historical control group are not perfectly balanced because the case number in
      the stage III subgroup of the control group is small. CONCLUSIONS: pN staging
      proved to be a robust prognostic marker in colorectal cancer under the
      circumstances of improved lymph node harvest. After adaptation of the cutoff
      values, lymph node ratio is also prognostic but not superior to pN staging.

PMID- 27050601
TI  - Tumor Budding Detection by Immunohistochemical Staining is Not Superior to
      Hematoxylin and Eosin Staining for Predicting Lymph Node Metastasis in pT1
      Colorectal Cancer.
AB  - BACKGROUND: Tumor budding is recognized as an important risk factor for lymph
      node metastasis in pT1 colorectal cancer. Immunohistochemical staining for
      cytokeratin has the potential to improve the objective diagnosis of tumor budding
      over detection based on hematoxylin and eosin staining. However, it remains
      unclear whether tumor budding detected by immunohistochemical staining is a
      significant predictor of lymph node metastasis in pT1 colorectal cancer.
      OBJECTIVE: The purpose of this study was to clarify the clinical significance of
      tumor budding detected by immunohistochemical staining in comparison with that
      detected by hematoxylin and eosin staining. DESIGN: This was a retrospective
      study. SETTINGS: The study was conducted at Niigata University Medical & Dental
      Hospital. PATIENTS: We enrolled 265 patients with pT1 colorectal cancer who
      underwent surgery with lymph node dissection. MAIN OUTCOME MEASURES: Tumor
      budding was evaluated by both hematoxylin and eosin and immunohistochemical
      staining with the use of CAM5.2 antibody. Receiver operating characteristic curve
      analyses were conducted to determine the optimal cutoff values for tumor budding
      detected by hematoxylin and eosin and CAM5.2 staining. Univariate and
      multivariate analyses were performed to identify the significant factors for
      predicting lymph node metastasis. RESULTS: Receiver operating characteristic
      curve analyses revealed that the cutoff values for tumor budding detected by
      hematoxylin and eosin and CAM5.2 staining for predicting lymph node metastases
      were 5 and 8. On multivariate analysis, histopathological differentiation (OR,
      6.21; 95% CI, 1.16-33.33; p = 0.03) and tumor budding detected by hematoxylin and
      eosin staining (OR, 4.91; 95% CI, 1.64-14.66; p = 0.004) were significant
      predictors for lymph node metastasis; however, tumor budding detected by CAM5.2
      staining was not a significant predictor. LIMITATIONS: This study was limited by
      potential selection bias because surgically resected specimens were collected
      instead of endoscopically resected specimens. CONCLUSIONS: Tumor budding detected
      by CAM5.2 staining was not superior to hematoxylin and eosin staining for
      predicting lymph node metastasis in pT1 colorectal cancer.

PMID- 27050602
TI  - Early Outcomes of Endoscopic Submucosal Dissection for Colorectal Neoplasms
      According to Clinical Indications.
AB  - BACKGROUND: Although endoscopic submucosal dissection has been shown to be safe
      and effective for colorectal tumors, its clinical outcomes vary. OBJECTIVE: The
      aim of this study is to assess the outcomes of endoscopic submucosal dissection
      according to clinical indications. DESIGN: This is a prospective, multicenter,
      single-arm study. SETTING: The study was conducted at special hospitals for
      colorectal diseases and cancers. PATIENTS: The study population included
      consecutive patients aged 20 to 80 years who underwent colorectal endoscopic
      submucosal dissection for 1) early colorectal cancer, 2) laterally spreading
      tumors >=2 cm in diameter, and 3) submucosal tumors. INTERVENTIONS: Procedures
      were performed by experienced colonoscopists. MAIN OUTCOME MEASURES: The primary
      end points were en bloc and curative resection rates. En bloc resection was
      defined as endoscopic one-piece resection without tumor fragmentation. Curative
      resection was defined as en bloc resection and no pathologic requirement for
      additional surgery. Secondary end points included procedure time, complications,
      and hospital stay. RESULTS: Of 321 patients, 317 (98.8%) underwent en bloc
      resection and 231 (72.0%) underwent curative resection. The mean procedure time
      was 46.2 minutes. Mean hospital stay after the procedure was 3.1 days.
      Perforation occurred in 2 patients (0.6%), and bleeding occurred in 10 (3.1%)
      patients. All patients with complications were treated by endoscopic clipping or
      nonoperative management. Fifteen patients (4.7%) underwent additional radical
      surgery owing to the risks of lymph node metastasis. Although tumor size was
      smaller and procedure time shorter in the submucosal tumor group than in the
      laterally spreading tumor or early colorectal cancer group, there were no
      differences in clinical outcomes including en bloc and curative resection rates.
      Submucosal fibrosis was the only factor affecting endoscopic submucosal
      dissection procedure-related complications. LIMITATIONS: Early outcomes in a
      limited population and the potential for selection bias were limitations of this
      study. CONCLUSIONS: Outcomes of colorectal endoscopic submucosal dissection were
      acceptable in selected patients, with no difference in outcomes according to
      clinical indications. Because submucosal fibrosis can increase complications, it
      should be minimized before endoscopic submucosal dissection.

PMID- 27050603
TI  - Large Variation in Blood Transfusion Use After Colorectal Resection: A Call to
      Action.
AB  - BACKGROUND: Perioperative blood transfusions are associated with an increased
      risk of adverse postoperative outcomes through immunomodulatory effects.
      OBJECTIVE: The purpose of this study was to identify factors associated with
      variation in blood transfusion use after elective colorectal resection and
      associated postoperative infectious complications DESIGN: This was a
      retrospective cohort study. SETTINGS: The study included elective colorectal
      resections in New York State from 2001 to 2013. PATIENTS: The study cohort
      consists of 125,160 colorectal resections. Patients who were admitted
      nonelectively or who were admitted before the date of surgery were excluded. MAIN
      OUTCOME MEASURES: Receipt of a perioperative allogeneic red blood cell
      transfusion and the secondary end points of postoperative pneumonia, surgical
      site infection, intra-abdominal abscess, and sepsis were measured. RESULTS: The
      overall rate of perioperative blood transfusion for the study cohort was 13.9%.
      The unadjusted blood transfusion rates ranged from 2.4% to 58.7% for individual
      surgeons and 2.9% to 32.8% for individual hospitals. After controlling for
      patient-, surgeon-, and hospital-level factors in a 3-level mixed-effects
      multivariable model, significant variation was still present across both surgeons
      (p < 0.0001) and hospitals (p < 0.0001), with a 16.8-fold difference in adjusted
      blood transfusion rates across surgeons and a 13.2-fold difference in adjusted
      blood transfusion rates across hospitals. Receipt of a blood transfusion was also
      independently associated with pneumonia (OR = 3.23 (95% CI, 2.92-3.57)), surgical
      site infection (OR = 2.27 (95% CI, 2.14-2.40)), intra-abdominal abscess (OR =
      2.72 (95% CI, 2.41-3.07)), and sepsis (OR = 4.51 (95% CI, 4.11-4.94)).
      LIMITATIONS: Limitations include the retrospective design and the possibility of
      miscoding within administrative data. CONCLUSIONS: Large surgeon- and hospital
      level variations in perioperative blood transfusion use for patients undergoing
      colorectal resection are present despite controlling for patient-, surgeon-, and
      hospital-level factors. In addition, receipt of a blood transfusion was
      independently associated with an increased risk of postoperative infectious
      complications. These findings support the creation and implementation of
      perioperative blood transfusion protocols aimed at limiting unwarranted
      variation.

PMID- 27050604
TI  - Readmissions After Colectomy: The Upstate New York Surgical Quality Initiative
      Experience.
AB  - BACKGROUND: Hospital readmissions remain a major medical and financial concern to
      the healthcare system and have become an area of interest in health outcomes
      performance metrics. There is a pressing need to identify process measures that
      may help reduce readmissions. OBJECTIVE: Our aim was to assess the patient
      characteristics and surgical factors associated with 30-day readmissions for
      colorectal surgery in Upstate New York. DESIGN: This was a retrospective cohort
      study. SETTINGS: The study included colectomy cases abstracted for the National
      Surgical Quality Improvement Program in the Upstate New York Surgical Quality
      Initiative from June 2013 to June 2014. PATIENTS: The study consists of 630
      colectomies. Patients with a length of stay >30 days or who died during the index
      admission were excluded. MAIN OUTCOME MEASURES: Readmission within 30 days of
      surgery was the main outcome measure. RESULTS: Of 630 colectomy patients, 76
      patients (12%) were readmitted within 30 days of surgery. Major and minor
      complications were associated with 30-day postoperative readmission (OR = 2.99
      (95% CI, 1.70-5.28) and OR = 2.19 (95% CI, 1.09-4.43)) but excluded from final
      analysis because they included both predischarge and postdischarge complications.
      Risk factors independently associated with 30-day postoperative readmission
      included diabetes mellitus (OR = 1.94 (95% CI, 1.02-3.67)), smoker within the
      past year (OR = 2.01 (95% CI, 1.12-3.60)), no scheduled follow-up (OR = 2.20 (95%
      CI, 1.25-3.86)), and ileostomy formation (OR = 1.97 (95% CI, 1.03-3.77)).
      LIMITATIONS: Limitations include the retrospective design and only 30 days of
      postoperative follow-up. CONCLUSIONS: Consistent with national trends, 1 in 8
      patients in the Upstate New York Surgical Quality Initiative program was
      readmitted within 30 days after colorectal surgery. This study identified several
      risk factors that may act as tangible targets for intervention, including
      preoperative smoking cessation programs, optimization of diabetic management,
      mandatory scheduled follow-up appointments on discharge, and ostomy care
      pathways.

PMID- 27050605
TI  - Topographic Anatomy of the Anal Sphincter Complex and Levator Ani Muscle as It
      Relates to Intersphincteric Resection for Very Low Rectal Disease.
AB  - BACKGROUND: Intersphincteric resection has become a widely used treatment for
      patients with rectal cancer. However, the detailed anatomy of the anal canal
      related to this procedure has remained unclear. OBJECTIVE: The purpose of this
      study was to clarify the detailed anatomy of the anal canal. DESIGN: This is a
      descriptive study. SETTINGS: Histologic evaluations of paraffin-embedded tissue
      specimens were conducted at a tertiary referral hospital. PATIENTS: Tissue
      specimens were obtained from cadavers of 5 adults and from 13 patients who
      underwent abdominoperineal resection for rectal cancer. MAIN OUTCOME MEASURES:
      Sagittal sections from 9 circumferential portions of the cadaveric anal canal
      (histologic staining) and 3 circumferential portions from patients were studied
      (immunohistochemistry for smooth and skeletal muscle fibers). RESULTS:
      Longitudinal fibers between the internal and external anal sphincters consisted
      primarily of smooth muscle fibers that continued from the longitudinal muscle of
      the rectum. The levator ani muscle attached directly to the lateral surface of
      the longitudinal smooth muscle of the rectum. The length of the attachment was
      longer in the anterolateral portion and shorter in the posterior portion of the
      anal canal. In the lateral and posterior portions, the levator ani muscle
      partially overlapped the external anal sphincter; however, there was less overlap
      in the anterolateral portion. In the posterior portion, thick smooth muscle was
      present on the surface of the levator ani muscle and it continued to the
      longitudinal muscle of the rectum. LIMITATIONS: We observed only limited portions
      in some surgical specimens because of obstruction by tumors. CONCLUSIONS: The
      levator ani muscle attaches directly to the longitudinal muscle of the rectum.
      The spatial relationship between the smooth and skeletal muscles differed in
      different portions of the anal canal. For intersphincteric resection, dissection
      must be performed between the longitudinal muscle of the rectum and the levator
      ani muscle/external anal sphincter, and the appropriate surgical lines must be
      selected based on the specific structural characteristics of each portion.

PMID- 27050606
TI  - Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter
      Anatomy and Function in a Rat Model at a Time Remote From Injury.
AB  - BACKGROUND: We have explored cell-based therapy to aid anal sphincter repair, but
      a conditioning injury is required to direct stem cells to the site of injury
      because symptoms usually manifest at a time remote from injury. OBJECTIVE: We
      aimed to investigate the effect of local electrical stimulation followed by
      mesenchymal stem cell delivery on anal sphincter regeneration at a time remote
      from injury. DESIGN AND MAIN OUTCOME MEASURES: With the use of a rat model,
      electrical stimulation parameters and cell delivery route were selected based on
      in vivo cytokine expression and luciferase-labeled cell imaging of the anal
      sphincter complex. Three weeks after a partial anal sphincter excision, rats were
      randomly allocated to 4 groups based on different local interventions: no
      treatment, daily electrical stimulation for 3 days, daily stimulation for 3 days
      followed by stem cell injection on the third day, and daily electrical
      stimulation followed by stem cell injection on the first and third days.
      Histology-assessed anatomy and anal manometry evaluated physiology 4 weeks after
      intervention. RESULTS: The electrical stimulation parameters that significantly
      upregulated gene expression of homing cytokines also achieved mesenchymal stem
      cell retention when injected directly in the anal sphincter complex in comparison
      with intravascular and intraperitoneal injections. Four weeks after intervention,
      there was significantly more new muscle in the area of injury and significantly
      improved anal resting pressure in the group that received daily electrical
      stimulation for 3 days followed by a single injection of 1 million stem cells on
      the third day at the site of injury. LIMITATION: This was a pilot study and
      therefore was not powered for functional outcome. CONCLUSIONS: In this rat injury
      model with optimized parameters, electrical stimulation with a single local
      mesenchymal stem cell injection administered 3 weeks after injury significantly
      improved both new muscle formation in the area of injury and anal sphincter
      pressures.

PMID- 27050607
TI  - Systematic Review of Surgical Treatments for Fecal Incontinence.
AB  - BACKGROUND: No systematic review has examined the collective randomized and
      nonrandomized evidence for fecal incontinence treatment effectiveness across the
      range of surgical treatments. OBJECTIVE: The purpose of this study was to assess
      the efficacy, comparative effectiveness, and harms of surgical treatments for
      fecal incontinence in adults. DATA SOURCES: Ovid MEDLINE, EMBASE, Physiotherapy
      Evidence Database, Cumulative Index to Nursing and Allied Health Literature,
      Allied and Complementary Medicine, and the Cochrane Central Register of
      Controlled Trials, as well as hand searches of systematic reviews, were used as
      data sources. STUDY SELECTION: Two investigators screened abstracts for
      eligibility (surgical treatment of fecal incontinence in adults, published 1980
      2015, randomized controlled trial or observational study with comparator; case
      series were included for adverse effects). Full-text articles were reviewed for
      patient-reported outcomes. We extracted data, assessed study risk of bias, and
      evaluated strength of evidence for each treatment-outcome combination.
      INTERVENTIONS: Surgical treatments for fecal incontinence were included
      interventions. MAIN OUTCOME MEASURES: Fecal incontinence episodes/severity,
      quality of life, urgency, and pain were measured. RESULTS: Twenty-two studies met
      inclusion criteria (13 randomized trials and 9 observational trials); 53 case
      series were included for harms. Most patients were middle-aged women with mixed
      FI etiologies. Intervention and outcome heterogeneity precluded meta-analysis.
      Evidence was insufficient for all of the surgical comparisons. Few studies
      examined the same comparisons; no studies were high quality. Functional
      improvements varied; some authors excluded those patients with complications or
      lost to follow-up from analyses. Complications ranged from minor to major
      (infection, bowel obstruction, perforation, and fistula) and were most frequent
      after the artificial bowel sphincter (22%-100%). Major surgical complications
      often required reoperation; few required permanent colostomy. LIMITATIONS: Most
      evidence is intermediate term, with small patient samples and substantial
      methodologic limitations. CONCLUSIONS: Evidence was insufficient to support
      clinical or policy decisions for any surgical treatments for fecal incontinence
      in adults. More invasive surgical procedures had substantial complications. The
      lack of compliance with study reporting standards is a modifiable impediment in
      the field. Future studies should focus on longer-term outcomes and attempt to
      identify subgroups of adults who might benefit from specific procedures.

PMID- 27050608
TI  - Perineal Sigmoidectomy for Prolapse of a Side-to-End Handsewn Coloanal
      Anastomosis.

PMID- 27050609
TI  - A Mechanical Explanation for the Development of Enteroatmospheric Fistulas in
      Open Abdomen.

PMID- 27050610
TI  - Efficacy of Fissurectomy and Botox for Chronic Anal Fissure.

PMID- 27050611
TI  - The Author Replies.

PMID- 27050612
TI  - Supralevator Extension in Fistula-in-Ano Is Almost Always in the Intersphincteric
      Plane: Easy Solution for a Complex Disease.

PMID- 27050613
TI  - The Author Replies.

PMID- 27050616
TI  - A novel role for the root cap in phosphate uptake and homeostasis.
AB  - The root cap has a fundamental role in sensing environmental cues as well as
      regulating root growth via altered meristem activity. Despite this well
      established role in the control of developmental processes in roots, the root
      cap's function in nutrition remains obscure. Here, we uncover its role in
      phosphate nutrition by targeted cellular inactivation or phosphate transport
      complementation in Arabidopsis, using a transactivation strategy with an
      innovative high-resolution real-time (33)P imaging technique. Remarkably, the
      diminutive size of the root cap cells at the root-to-soil exchange surface
      accounts for a significant amount of the total seedling phosphate uptake
      (approximately 20%). This level of Pi absorption is sufficient for shoot biomass
      production (up to a 180% gain in soil), as well as repression of Pi starvation
      induced genes. These results extend our understanding of this important tissue
      from its previously described roles in environmental perception to novel
      functions in mineral nutrition and homeostasis control. 

PMID- 27050617
TI  - May I check your cap?
AB  - Modernizing a classic technique to study microtubules has revealed that the
      stability of a microtubule is related to its growth rate.

PMID- 27050618
TI  - Millimeter-area, free standing, phospholipid bilayers.
AB  - Minimal model biomembrane studies have the potential to unlock the fundamental
      mechanisms of cellular function that govern the processes upon which life relies.
      However, existing methods to fabricate free-standing model membranes currently
      have significant limitations. Bilayer sizes are often tens of micrometers,
      decoupling curvature or substrate effects, orthogonal control over tension, and
      solvent exchange combined with microscopy techniques is not possible, which
      restricts the studies that can be performed. Here, we describe a versatile
      platform to generate free standing, planar, phospholipid bilayers with millimeter
      scale areas. The technique relies on an adapted thin-film balance apparatus
      allowing for the dynamic control of the nucleation and growth of a planar black
      lipid membrane in the center of an orifice surrounded by microfluidic channels.
      Success is demonstrated using several different lipid types, including mixtures
      that show the same temperature dependent phase separation as existing protocols,
      moreover, membranes are highly stable. Two advantages unique to the proposed
      method are the dynamic control of the membrane tension and the possibility to
      make extremely large area membranes. We demonstrate this by showing how a block
      polymer, F68, used in drug delivery increases the membrane compliance. Together,
      the results demonstrate a new paradigm for studying the mechanics, structure, and
      function of model membranes.

PMID- 27050619
TI  - Get Vaccinated! and Get Tested! Developing Primary and Secondary Cervical Cancer
      Prevention Videos for a Haitian Kreyol-Speaking Audience.
AB  - Although routine screening reduces cervical cancer rates between 60% and 90%,
      thousands of women worldwide are diagnosed with the disease on an annual basis
      because of inadequate screening. Haitian women in South Florida experience a
      disproportionate burden of cervical cancer, with disease rates 4 times higher
      than the average for women in Miami. An ongoing community-based participatory
      research initiative to assess and reduce this burden has revealed that a complex
      interplay of factors contributes to a lack of access to screening in this
      community, including socioeconomics, language barriers, and traditional
      understandings of health and disease. In an effort to address some of these
      barriers and encourage uptake of primary and secondary cervical cancer prevention
      strategies, 2 videos on cervical cancer prevention were created using a community
      based participatory research framework. The video screenplays were created by a
      Haitian screenwriter using evidence-based medical information provided by
      academic researchers. The films feature Haitian actors speaking a Haitian Kreyol
      dialogue with a storyline portraying friends and family discussing human
      papillomavirus disease and vaccination, Papanicolaou testing, and cervical
      cancer. Focus groups held with Haitian women in South Florida suggested that the
      films are engaging; feature relatable characters; and impact knowledge about
      human papillomavirus, cervical cancer development, and current prevention
      recommendations.

PMID- 27050620
TI  - Impingement of the Mobile Bearing on the Lateral Wall of the Tibial Tray in
      Unicompartmental Knee Arthroplasty.
AB  - BACKGROUND: Tilting of the mobile bearing relative to the tibial tray in the
      flexion position may result from the implantation of femoral components more
      laterally relative to tibial components during unicompartmental knee arthroplasty
      (UKA) using the Oxford Knee. The purpose of the present study was to compare
      femoral component positions after UKA using the phase 3 device and a novel
      device. We further evaluated the placement of the femoral components with the new
      device in the flexion position to determine the association with short-term
      prognosis. METHODS: The location of femoral and tibial components in the flexion
      position of 38 knees implanted using the phase 3 device and 49 knees using a
      novel device was assessed at 1 year postoperatively using radiography of the
      proximal tibia and distal femur in the flexion position. RESULTS: The femoral
      component was implanted more laterally using the new device than using the phase
      3 device in the flexion position (P = .012), which caused the impingement of the
      mobile bearing against the lateral wall of the tibial tray. After UKA using the
      new device, 10% of patients exhibited the tilting phenomenon of the mobile
      bearing because of the lateral implantation of the femoral implant. CONCLUSION:
      To prevent implantation of the femoral component too laterally using the new
      device during UKA, knee surgeons should set the drill guide more medially such
      that the center of the drill is aligned with the middle of the medial femoral
      condyle.

PMID- 27050621
TI  - Bone mass in girls according to their BMI, VO2 max, hours and years of practice.
AB  - The accumulation of bone mass during puberty is related with bone health in
      adulthood. This accumulation is influenced by diverse factors such as body mass
      index (BMI), maximal oxygen uptake (VO2 max), hours of training and years of
      sport practice. For this reason, the objective of this study is to analyse the
      influence of these variables on bone mass in young female athletes. The sample is
      formed of 120 healthy girls with ages between 9 and 13 (11.32 +/- 1.6 years old),
      divided into two groups depending on their BMI, VO2 max, hours of training and
      years of sport practice. The participants completed a series of tests to evaluate
      level of sexual development, body composition (fat mass, lean mass and bone mass)
      and physical condition. The results show higher values of total lean mass, total
      fat mass and percentage of body fat in the groups with higher BMI in prepubertal
      girls and pubertal girls (p < .05). In relation to VO2 max, in the prepubertal
      group, girls with lower VO2 max had higher values of total fat mass (p < .05) and
      percentage of body fat (p < .05). In the pubertal group, girls with lower VO2 max
      also showed a higher total fat mass (p < .05). The studied variables account for
      a 85% and 75.4% of the variance of total bone mineral content and bone mineral
      density (BMD), respectively. In conclusion, the content and BMD are closely
      related with muscle mass and sports practice in young females. The amount of fat
      mass showed no association with bone mass and physical condition has an indirect
      relationship with bone development. 

PMID- 27050622
TI  - Gd(III)-Dithiolane Gold Nanoparticles for T1-Weighted Magnetic Resonance Imaging
      of the Pancreas.
AB  - Pancreatic adenocarcinoma has a 5 year survival of approximately 3% and median
      survival of 6 months and is among the most dismal of prognoses in all of
      medicine. This poor prognosis is largely due to delayed diagnosis where patients
      remain asymptomatic until advanced disease is present. Therefore, techniques to
      allow early detection of pancreatic adenocarcinoma are desperately needed.
      Imaging of pancreatic tissue is notoriously difficult, and the development of new
      imaging techniques would impact our understanding of organ physiology and
      pathology with applications in disease diagnosis, staging, and longitudinal
      response to therapy in vivo. Magnetic resonance imaging (MRI) provides numerous
      advantages for these types of investigations; however, it is unable to delineate
      the pancreas due to low inherent contrast within this tissue type. To overcome
      this limitation, we have prepared a new Gd(III) contrast agent that accumulates
      in the pancreas and provides significant contrast enhancement by MR imaging. We
      describe the synthesis and characterization of a new dithiolane-Gd(III) complex
      and a straightforward and scalable approach for conjugation to a gold
      nanoparticle. We present data that show the nanoconjugates exhibit very high per
      particle values of r1 relaxivity at both low and high magnetic field strengths
      due to the high Gd(III) payload. We provide evidence of pancreatic tissue
      labeling that includes MR images, post-mortem biodistribution analysis, and
      pancreatic tissue evaluation of particle localization. Significant contrast
      enhancement was observed allowing clear identification of the pancreas with
      contrast-to-noise ratios exceeding 35:1.

PMID- 27050623
TI  - Fluoride-induced modulation of ionic transport in asymmetric nanopores
      functionalized with "caged" fluorescein moieties.
AB  - We demonstrate experimentally and theoretically a nanofluidic fluoride sensing
      device based on a single conical pore functionalized with "caged" fluorescein
      moieties. The nanopore functionalization is based on an amine-terminated
      fluorescein whose phenolic hydroxyl groups are protected with tert
      butyldiphenylsilyl (TBDPS) moieties. The protected fluorescein (Fcn-TBDPS-NH2)
      molecules are then immobilized on the nanopore surface via carbodiimide coupling
      chemistry. Exposure to fluoride ions removes the uncharged TBDPS moieties due to
      the fluoride-promoted cleavage of the silicon-oxygen bond, leading to the
      generation of negatively charged groups on the fluorescein moieties immobilized
      onto the pore surface. The asymmetrical distribution of these groups along the
      conical nanopore leads to the electrical rectification observed in the current
      voltage (I-V) curve. On the contrary, other halides and anions are not able to
      induce any significant ionic rectification in the asymmetric pore. In each case,
      the success of the chemical functionalization and deprotection reactions is
      monitored through the changes observed in the I-V curves before and after the
      specified reaction step. The theoretical results based on the Nernst-Planck and
      Poisson equations further demonstrate the validity of an experimental approach to
      fluoride-induced modulation of nanopore current rectification behaviour. 

PMID- 27050624
TI  - Mycophenolate mofetil and curcumin provide comparable therapeutic benefit in
      experimental chronic kidney disease: role of Nrf2-Keap1 and renal dopamine
      pathways.
AB  - Increased oxidative stress and inflammation have an important role in the
      pathophysiology of chronic kidney disease (CKD). On the other hand, more
      affordable therapeutic alternatives for treating this disease are urgently
      needed. Therefore, we compared the therapeutic efficacy of curcumin and
      mycophenolate mofetil (MMF) in 5/6 nephrectomy (5/6 Nx) model of CKD. Also, we
      evaluated whether both compounds provide benefit through the preservation of
      similar antioxidant mechanisms. Four groups of male Wistar were studied over a
      period of 4 wk. Control sham group (n= 12), 5/6 Nx (n = 12), 5/6 Nx + MMF (30
      mg/k BW/day, n = 11) and 5/6 Nx + Curcumin (120 mg/k BW/day, n = 12). Renal
      function and markers of oxidative stress and inflammation were evaluated. Also
      Nrf2-Keap1 and renal dopamine, antioxidant pathways were assessed. 5/6 Nx induced
      an altered renal autoregulation response, proteinuria, and hypertension; these
      effects were in association with increased oxidative stress, endothelial
      dysfunction and renal inflammation. The mechanisms associated with these
      alterations included a reduced nuclear translocation of Nrf2 and
      hyperphosphorylation of dopamine D1 receptor with a concurrent overactivation of
      renal NADPH oxidase. Treatments with MMF and curcumin provided equivalent
      therapeutic efficacy as both prevented functional renal alterations as well as
      preserved antioxidant capacity and avoided renal inflammatory infiltration.
      Moreover, both treatments preserved Nrf2-Keap1 and renal dopamine antioxidant
      pathways. In summary, therapeutic strategies aimed to preserve renal antioxidant
      pathways can help to retard the progression of CKD. 

PMID- 27050625
TI  - Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective
      and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors.
AB  - G protein-coupled receptors (GPCRs) are central to many physiological processes.
      Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs),
      some of which have been implicated in heart failure. GSK180736A, developed as a
      Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an
      inhibitor of GRK2 and co-crystallized in the active site. Guided by its binding
      pose overlaid with the binding pose of a known potent GRK2 inhibitor, Takeda103A,
      a library of hybrid inhibitors was developed. This campaign produced several
      compounds possessing high potency and selectivity for GRK2 over other GRK
      subfamilies, PKA, and ROCK1. The most selective compound, 12n (CCG-224406), had
      an IC50 for GRK2 of 130 nM, >700-fold selectivity over other GRK subfamilies, and
      no detectable inhibition of ROCK1. Four of the new inhibitors were crystallized
      with GRK2 to give molecular insights into the binding and kinase selectivity of
      this class of inhibitors.

PMID- 27050626
TI  - Estimating population food and nutrient exposure: a comparison of store survey
      data with household panel food purchases.
AB  - Population exposure to food and nutrients can be estimated from household food
      purchases, but store surveys of foods and their composition are more available,
      less costly and might provide similar information. Our aim was to compare
      estimates of nutrient exposure from a store survey of packaged food with those
      from household panel food purchases. A cross-sectional store survey of all
      packaged foods for sale in two major supermarkets was undertaken in Auckland, New
      Zealand, between February and May 2012. Longitudinal household food purchase data
      (November 2011 to October 2012) were obtained from the nationally representative,
      population-weighted New Zealand Nielsen HomeScan(r) panel. Data on 8440 packaged
      food and non-alcoholic beverage products were collected in the store survey. Food
      purchase data were available for 1229 households and 16 812 products. Store
      survey data alone produced higher estimates of exposure to Na and sugar compared
      with estimates from household panel food purchases. The estimated mean difference
      in exposure to Na was 94 (95 % CI 72, 115) mg/100 g (20 % relative difference;
      P<0.01), to sugar 1.6 (95 % CI 0.8, 2.5) g/100 g (11 %; P<0.01), to SFA -0.3 (95
      % CI -0.8, 0.3) g/100 g (6 %; P=0.3) and to energy -18 (-71, 35) kJ/100 g (2 %;
      P=0.51). Compared with household panel food purchases, store survey data provided
      a reasonable estimate of average population exposure to key nutrients from
      packaged foods. However, caution should be exercised in using such data to
      estimate population exposure to Na and sugar and in generalising these findings
      to other countries, as well as over time. 

PMID- 27050627
TI  - Impact of vascular access on acute kidney injury after percutaneous coronary
      intervention.
AB  - OBJECTIVES: We performed a systematic review of the literature and a meta
      analysis to examine the role of access site in affecting the incidence of acute
      kidney injury (AKI) after percutaneous coronary intervention (PCI). BACKGROUND:
      The vascular access site may play a central role among procedure-related risk
      factors for AKI after PCI. Transradial access is associated with reduced vascular
      complications and major bleeding which, in turn, is an emerging risk factor for
      post-procedural AKI. METHODS: Results of six observational studies, three out of
      six providing propensity matching adjustment, of patients undergoing PCI from the
      radial and the femoral access were pooled, including overall 26,185 patients. The
      endpoint was the incidence of study-defined AKI. A meta-regression analysis was
      performed to further assess the role of study-level covariates. Random-effects
      models were privileged. RESULTS: There was a significant difference in the
      incidence of AKI after PCI, favoring radial access (odds ratio [OR] 0.51, 95% CI
      0.39-0.67, p<0.0001), and the effect size was larger in studies including only
      patients presenting with ST-elevation myocardial infarction (STEMI) (OR 0.42, 95%
      CI 0.24-0.72, p=0.001). The meta-regression showed a significant relationship
      between the benefit of radial access and the proportion of STEMI patients
      (p=0.031) in each of the included studies. CONCLUSIONS: Transradial intervention
      is associated with a reduction in the incidence of AKI after PCI, as compared to
      the femoral access, and this benefit is more evident in STEMI patients. These
      findings warrant further confirmation in randomized controlled trials.

PMID- 27050628
TI  - Computerized Working Memory Training for Children with Moderate to Severe
      Traumatic Brain Injury: A Double-Blind, Randomized, Placebo-Controlled Trial.
AB  - Pediatric traumatic brain injury (TBI) places children at risk for deficits in
      working memory (WM; comprising a central executive [CE], and two storage systems:
      phonological loop [PL] and visuospatial sketchpad [VSSP]), which is strongly
      related to attention and academic skills in childhood. This study aimed to
      examine whether different components of WM can be improved following adaptive WM
      training (Cogmed) and whether improvements in WM generalize to other cognitive
      (attention) and academic skills (reading and mathematics) in children with TBI.
      Twenty-seven children with moderate to severe TBI were randomized to adaptive
      (Cogmed; n = 13) or non-adaptive training (active placebo; n = 14) and evaluated
      at baseline, post-training, and 3-months follow-up. Three children in the
      adaptive group and one child in the non-adaptive group withdrew from the study
      before completion of training. Complete case (CC) and intention-to-treat (ITT)
      analyses were conducted. Children in the adaptive group demonstrated
      significantly greater gains on select WM tasks (VSSP, but not PL or CE) from pre-
      to post-training (pre-post) and pre-training to follow-up (pre-follow-up; CC and
      ITT analyses). No gains were found on tests of attention. Adaptive training
      resulted in significantly greater gains on select academic skills (reading, but
      not mathematics): reading comprehension pre-post-training (ITT analyses) and
      reading accuracy pre-follow-up (CC and ITT analyses). This first, to our
      knowledge, study to examine the efficacy of adaptive WM training for children
      with TBI provides preliminary evidence of near and far transfer of training to WM
      and academic skills, respectively.

PMID- 27050629
TI  - Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles
      containing clotrimazole for oral candidiasis treatment.
AB  - Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have
      been developed as an alternative for oral candidiasis treatment. NSCS was
      synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated
      into the micelles using various methods, including the dropping method, the
      dialysis method, and the O/W emulsion method. The size and morphology of the CZ
      loaded micelles were characterized using dynamic light scattering measurements
      (DLS) and a transmission electron microscope (TEM), respectively. The drug
      entrapment efficiency, loading capacity, release characteristics, and antifungal
      activity against Candida albicans were also evaluated. The CZ-loaded micelles
      prepared using different methods differed in the size of micelles. The micelles
      ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion
      method offered the highest percentage entrapment efficiency and loading capacity.
      The CZ released from the CZ-loaded micelles at much faster rate compared to CZ
      powder. The CZ-loaded NSCS micelles can significantly hinder the growth of
      Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal
      activity and might be further developed to be a promising candidate for oral
      candidiasis treatment.

PMID- 27050630
TI  - Neither boosted elvitegravir nor darunavir with emtricitabine/tenofovir
      disoproxil fumarate increase insulin resistance in healthy volunteers: results
      from the STRIBILD-IR study.
AB  - BACKGROUND: Insulin resistance (IR) was one of the first reported complications
      in HIV-positive patients who were receiving antiretroviral therapy (ART).
      However, the metabolic effects of newer fixed-dose ART combinations are unclear.
      METHODS: This Phase I prospective randomized open-label study evaluated the
      effects on IR in 30 healthy volunteers who were receiving newer fixed-dose
      combinations of tenofovir disoproxil fumarate, emtricitabine, elvitegravir and
      cobicistat (E/C/F/TDF, 10 patients) or the established ART regimens, such as
      tenofovir disoproxil fumarate/emtricitabine with lopinavir/ritonavir
      (F/TDF+LPV/r, 9 patients) or darunavir/ritonavir (F/TDF+DRV/r, 9 patients). IR
      was measured before and after the 14-day treatments using the hyperinsulinemic
      euglycemic clamp technique, and changes in IR were evaluated using the mean
      glucose disposal rate that was normalized to body weight (MBW) and lipid
      metabolism. RESULTS: The groups exhibited similar pretreatment IR, although MBW
      was significantly lower after the 14-day F/TDF+LPV/r treatment compared with
      baseline (12.5 +/-3.3 versus 9.2 +/-1.8 mg glucose/min*kg; P=0.037). No
      significant IR changes were observed for E/C/F/TDF (11.2 +/-3.2 versus 11.3 +/
      2.5) or F/TDF+DRV/r (11.6 +/-2.5 versus 11.3 +/-2.4). Compared with baseline,
      F/TDF+LPV/r and F/TDF+DRV/r treatments significantly increased day 14
      triglyceride levels (62 [54-73] versus 119 [77-147] mg/dl, P=0.0109; 75 [56-95]
      versus 96 [93-128] mg/dl, P=0.009, respectively). CONCLUSIONS: Short-term
      treatment using fixed-dose combinations of E/C/F/TDF or F/TDF+DRV/r did not
      affect IR, although IR significantly increased after treatment using F/TDF+LPV/r.

PMID- 27050631
TI  - Synthesis and Evaluation of a Library of Fluorescent Dipeptidomimetic Analogues
      as Substrates for Modified Bacterial Ribosomes.
AB  - Described herein are the synthesis and photophysical characterization of a
      library of aryl-substituted oxazole- and thiazole-based dipeptidomimetic
      analogues, and their incorporation into position 66 of green fluorescent protein
      (GFP) in lieu of the natural fluorophore. These fluorescent analogues resemble
      the fluorophore formed naturally by GFP. As anticipated, the photophysical
      properties of the analogues varied as a function of the substituents at the para
      position of the phenyl ring. The fluorescence emission wavelength maxima of
      compounds in the library varied from ~365 nm (near-UV region) to ~490 nm (visible
      region). The compounds also exhibited a large range of quantum yields (0.01
      0.92). The analogues were used to activate a suppressor tRNACUA and were
      incorporated into position 66 of GFP using an in vitro protein biosynthesizing
      system that employed engineered ribosomes selected for their ability to
      incorporate dipeptides. Four analogues with interesting photophysical properties
      and reasonable suppression yields were chosen, and the fluorescent proteins (FPs)
      containing these fluorophores were prepared on a larger scale for more detailed
      study. When the FPs were compared with the respective aminoacyl-tRNAs and the
      actual dipeptide analogues, the FPs exhibited significantly enhanced fluorescence
      intensities at the same concentrations. Part of this was shown to be due to the
      presence of the fluorophores as an intrinsic element of the protein backbone.
      There were also characteristic shifts in the emission maxima, indicating the
      environmental sensitivity of these probes. Acridon-2-ylalanine and oxazole 1a
      were incorporated into positions 39 and 66 of GFP, respectively, and were shown
      to form an efficient Forster resonance energy transfer (FRET) pair, demonstrating
      that the analogues can be used as FRET probes. 

PMID- 27050632
TI  - Doing the math on hepatitis C virus treatment.

PMID- 27050633
TI  - Comparison of serum paraoxonase and arylesterase activities between iron
      deficiency anemia patients and chronic kidney disease patients with anemia.
AB  - OBJECTIVE: Altered paraoxonase (PON) and arylesterase (ARE) activities have been
      shown in anemic chronic kidney disease (CKD) patients and in iron deficiency
      anemia (IDA) patients. Whether accompanying anemia alone is responsible for this
      diminished PON and ARE activities in CKD patients or an additive factor for this
      is not well studied. Therefore, we tried to clarify this issue here. METHODS: A
      total of 82 subjects that consisted of 19 patients with IDA (group 1), 23 anemic
      CKD patients (group 2), and 40 age and sex matched healthy subjects (group 3)
      were enrolled. Carotid intima media thickness (CIMT), serum total thiol (-SH),
      PON, and ARE activities of the participants were analyzed. RESULTS: Group 2
      patients had significantly lowest serum levels of Total -SH, PON and ARE. Further
      comparison showed that total -SH, PON and ARE levels were lower in group 1 than
      group 3 (p = 0.0001 in both). Regarding comparison of group 1 and 2, only serum
      ARE levels were significantly lower in group 2 (p = 0.001). PON activity was not
      different between group 1 and group 2 whereas ARE activity was lower in group 2
      than groups 1 and 3. In addition, correlation analysis showed that CIMT was
      negatively correlated with PON and ARE. CONCLUSIONS: This markedly decreased ARE
      activity in CKD patients, which could not be explained by the anemia alone, may
      have a role in the pathogenesis of increased atherosclerosis in such patients.
      Still further studies are needed to certain this.

PMID- 27050634
TI  - Induction of Microglial Activation by Mediators Released from Mast Cells.
AB  - BACKGROUND/AIMS: Microglia are the resident immune cells in the brain and play a
      pivotal role in immune surveillance in the central nervous system (CNS). Brain
      mast cells are activated in CNS disorders and induce the release of several
      mediators. Thus, brain mast cells, rather than microglia, are the "first
      responders" due to injury. However, the functional aspects of mast cell-microglia
      interactions remain uninvestigated. METHODS: Conditioned medium from activated
      HMC-1 cells induces microglial activation similar to co-culture of microglia with
      HMC-1 cells. Primary cultured microglia were examined by flow cytometry analysis
      and confocal microscopy. TNF- alpha and IL-6 were measured with commercial ELISA
      kits. Cell signalling was analysed by Western blotting. RESULTS: In the present
      study, we found that the conditioned medium from activated HMC-1 cells stimulated
      microglial activation and the subsequent production of the pro-inflammatory
      factors TNF-alpha and IL-6. Co-culture of microglia and HMC-1 cells with
      corticotropin-releasing hormone (CRH) for 24, 48 and 72 hours increased TNF-alpha
      and IL-6 production. Antagonists of histamine receptor 1 (H1R), H4R, proteinase
      activated receptor 2 (PAR2) or Toll-like receptor 4 (TLR4) reduced HMC-1-induced
      pro-inflammatory factor production and MAPK and PI3K/AKT pathway activation.
      CONCLUSIONS: These results imply that activated mast cells trigger microglial
      activation. Interactions between mast cells and microglia could constitute a new
      and unique therapeutic target for CNS inflammation-related diseases.

PMID- 27050635
TI  - Epidemiology of asthma-related disability in the U.S. Armed Forces: 2007-2012.
AB  - OBJECTIVE: To characterize the demographic, disability and deployment
      characteristics of U.S. Armed Forces personnel with an asthma-related disability
      discharge, which includes separation (without benefits) and retirement (with
      disability benefits). METHODS: Incidence rates for personnel evaluated for
      disability discharge and/or disability retired due to asthma and due to all other
      causes of disability discharge were calculated per 100,000 active duty enlisted
      service members by year. Multivariate logistical regression was used to examine
      the associations between disability retirement and several demographic and
      disability characteristics of service members evaluated for asthma-related
      disability discharge versus those evaluated for any other non-respiratory
      condition for each branch of military service. RESULTS: Service members evaluated
      for disability discharge related to asthma most often do not have comorbidity and
      are disability retired rather than separated, with rates of disability retirement
      increasing over time. Groups with a significantly higher incidence of evaluation
      for asthma-related disability include females, individuals who entered the
      military prior to the age of 20, non-Whites, and those with a history of
      deployment to Iraq or Afghanistan. The characteristic most associated with the
      odds of disability retirement was a history of deployment. CONCLUSIONS: New-onset
      asthma occurring after military entry often causes occupational impairment in
      service members, especially in those that have been deployed to Iraq or
      Afghanistan.

PMID- 27050636
TI  - Deep clinical remission: an optimised target in the management of rheumatoid
      arthritis? Experience from an ultrasonography study.
AB  - OBJECTIVES: Treat-to-target strategy, aiming at clinical remission, has greatly
      improved the prognosis of RA. However, ultrasonographic subclinical synovitis is
      correlated with bone erosion and disease flare. The aim of this study was to
      evaluate whether deeper clinical remission (DAS28(ESR)<=1.98) reflects the better
      control of subclinical synovitis. METHODS: One hundred and twenty-six RA patients
      in clinical remission were enrolled in the study. Disease activity and
      ultrasongraphy were evaluated at baseline, and every 3 months during a 12-month
      follow-up. The power Doppler (PD) synovitis and synovial hypertrophy (SH) of 22
      joints were recorded semi-quantitatively. The relationship between the extent of
      clinical remission, flare and ultrasonographic features was analysed. RESULTS: In
      126 RA patients, 76 achieved deep clinical remission (defined as
      DAS28(ESR)<=1.98) and 50 achieved mild clinical remission (defined as
      1.98<DAS28(ESR)<=2.6). At baseline, PD synovitis and SH were detectable in 25
      (32.9%) and 34 (44.7%) in 76 patients in deep clinical remission, which were
      significantly less compare with those in the mild group (32.9% vs. 72.0% and
      44.7% vs. 78.0%, p<0.01 for both). In all, 54 (42.9%) patients relapsed at
      average of 6.8+/-3.3 months during follow-up. Patients in deep remission
      possessed not only lower risk to relapse (30.3% vs. 62.0%, p<0.01), but also
      longer duration of remission before relapse (8.1+/-3.3 vs. 5.9+/-3.1 months,
      p<0.05). Besides, applying DAS28(ESR)<1.895 to predict ultrasonographic remission
      defined as negativity of both PD and SH was highly accurate (p<0.001).
      Subclinical PD synovitis at baseline was an independent risk factor for
      predicting relapse in RA patients achieved clinical remission (OR 8.8 [95% CI 2.7
      28.4]). CONCLUSIONS: Subclinical synovitis was common in RA patients even in deep
      clinical remission. The deeper the clinical remission, the milder the subclinical
      synovitis, and the lower risk to relapse. Therefore, achieving deeper clinical
      remission, which reflected better control of subclinical synovitis and less
      tendency to flare, could be an optimised treatment target of RA.

PMID- 27050637
TI  - Use of SolitaireTM retrievable stent-assisted coiling technique for endovascular
      treatment of post-traumatic direct carotid cavernous fistula.

PMID- 27050638
TI  - Sacroiliac joints imaging in axial spondyloarthritis.
AB  - Imaging of the sacroiliac joints is the key point in diagnosing and classifying
      spondyloarthritis. Since the integration of MRI criteria to the Assessment of
      Spondyloarhtitis Society (ASAS) classification in 2009, the attention was focused
      on the presence of bone marrow edema to characterize sacroiliitis. However,
      returning to basics and analysing structural signs is of utmost importance to
      avoid overdiagnosis of spondyloarthritis. 

PMID- 27050639
TI  - Effect of sherbet timing on distension and evaluation of the esophagus with
      multidetector-row computed tomography.
AB  - PURPOSE: The goal of this study was to analyze the effect of oral sherbet
      application on esophageal distension and esophageal evaluation with thoracic
      multidetector-row computed tomography (MDCT) regarding sherbet timing. MATERIALS
      AND METHODS: A total 120 patients (65 men, 55 women) with a mean age of 59.7
      years who were given 4g sherbet powder to be swallowed 60, 30 or 10seconds before
      thoracic MDCT were included. Inner esophageal diameter was measured in three
      planes at three anatomic levels. Area of esophageal lumen and assessable length
      of the esophagus were calculated and statistically analyzed using repeated
      measures-ANOVA and post-hoc-t-tests. Results were compared groupwise and intra
      individually with previous examinations without sherbet. RESULTS: Intra
      individual comparison and subgroup-analysis showed that esophageal distension was
      significantly better when sherbet was used (mean inner area: 1.98+/-0.66cm(2) vs.
      0.49+/-0.14cm(2)) (P<0.001). After preparation, in average 80.2% of the
      esophageal length were assessable compared to 39.2% without sherbet (P<0.001).
      Timing of sherbet administration within one minute before scan-start revealed no
      significant differences (P=0.9), yet a shorter delay to scan-start led to the
      best results. CONCLUSION: Oral sherbet administration within one minute before
      scan-start improves esophageal distension and evaluation using thoracic MDCT.
      This method of esophageal preparation is simple, can easily be applied in
      clinical routine and may improve the diagnosis of esophageal pathologies.

PMID- 27050640
TI  - Cysteinylation of a monoclonal antibody leads to its inactivation.
AB  - Post-translational modifications can have a signification effect on antibody
      stability. A comprehensive approach is often required to best understand the
      underlying reasons the modification affects the antibody's potency or aggregation
      state. Monoclonal antibody 001 displayed significant variation in terms of
      potency, as defined by surface plasmon resonance testing (Biacore), from lot to
      lot independent of any observable aggregation or degradation, suggesting that a
      post-translational modification could be driving this variability. Analysis of
      different antibody lots using analytical hydrophobic interaction chromatography
      (HIC) uncovered multiple peaks of varying size. Electrospray ionization mass
      spectrometry (ESI-MS) indicated that the antibody contained a cysteinylation post
      translational modification in complementarity-determining region (CDR) 3 of the
      antibody light chain. Fractionation of the antibody by HIC followed by ESI-MS and
      Biacore showed that the different peaks were antibody containing zero, one, or
      two cysteinylation modifications, and that the modification interferes with the
      ability of the modified antibody arm to bind antigen. Molecular modeling of the
      modified region shows that this oxidation of an unpaired cysteine in the antibody
      CDR would block a potential antigen binding pocket, suggesting an inhibition
      mechanism.

PMID- 27050641
TI  - Answers to comments about "Hyperglycemia is a risk factor for high-grade
      envenomations after European viper bites (Vipera spp.) in children".

PMID- 27050642
TI  - Magnetic nanoparticles: preparation methods, applications in cancer diagnosis and
      cancer therapy.
AB  - Super-paramagnetic iron oxide nanoparticles (SPIONs) have been widely explored as
      novel magnetic resonance imaging (MRI) contrast agents because of a combination
      of favorable super-paramagnetic properties, biodegradability, and surface
      properties. Among the numerous MNPs under examination, SPIONs have involved
      considerable interest due to their outstanding magnetic properties,
      biocompatibility, and biodegradability. This review debates the ABCs of MR
      imaging, reports and informs the state of the art of magnetic nanoparticles in
      cancer dealing the source of SPIONs' exclusive magnetic properties, recent
      progresses in MRI acquisition methods for detection of SPIONs.

PMID- 27050643
TI  - Aging and the Arts Online: Lessons Learned From Course Development and
      Implementation.
AB  - With the recent move toward competency-based gerontology education, incorporating
      humanities and arts will be necessary for accreditation. This article describes
      the pedagogical approaches and lessons learned during 5 years of development and
      implementation of an asynchronous online course in Aging and the Arts. Fifty
      graduate and undergraduate students participated in the course over five
      semesters. Discipline diversity increased subsequent to designation as a fine
      arts general education course. Students expressed appreciation for multimedia
      resources, an initial fear of creating a wiki, and online redundancy was reduced
      through increased community engagement that also augmented application in real
      world settings. The visual nature of arts and aging lends itself to a compelling
      and interactive online course experience that can be adapted to synchronous,
      hybrid, and face-to-face formats. Opportunities for community engaged learning
      will increase as art programs for older adults become more prevalent.

PMID- 27050644
TI  - Meconium Evacuation for Facilitating Feed Tolerance in Preterm Neonates: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: A delayed passage of meconium is considered as a risk factor for feed
      intolerance in preterm neonates. OBJECTIVES: The aim of this study was to review
      the effects of different therapeutic agents for meconium evacuation on feed
      tolerance in preterm neonates. METHODS: A systematic review of randomised
      controlled trials (RCTs) of different therapeutic agents for meconium evacuation
      in preterm neonates (gestation <32 weeks and/or birth weight <1,500 g) using the
      Cochrane systematic review methodology was undertaken. Databases including Google
      Scholar were searched in January 2016. The primary outcome was the time to reach
      full feeds (TFF; >=120 ml/kg feeds with stoppage of parenteral nutrition >24 h).
      Secondary outcomes included necrotising enterocolitis (NEC), weight at discharge
      and adverse effects. The results were summarised as per the GRADE guidelines.
      RESULTS: Six RCTs (2 each of glycerine suppository and enema, 1 normal saline
      enema and 1 oral osmotic contrast agent; n = 442) with a low or unclear risk of
      bias were included. The pooled estimate (random effects model) showed no
      reduction in TFF [mean difference (MD) -0.03, 95% CI -2.47, 2.41, p = 0.98; level
      of evidence: low]. No differences in NEC [risk ratio (RR) 1.71, 95% CI 0.63,
      4.65, p = 0.30; level of evidence: low] and weight at discharge (MD -0.08, 95% CI
      -0.30, 0.15, p = 0.50; level of evidence: low) were found. The trial assessing
      oral osmotic contrast agents reported a trend towards a higher incidence of NEC
      >= stage II. There were no other adverse effects. CONCLUSION: Limited low-quality
      evidence indicates that prophylactic glycerine suppository, small volume
      glycerine/normal saline enema or oral osmotic contrast agents to evacuate
      meconium did not reduce TFF in preterm neonates. Large, well-designed trials are
      essential to study this clinically significant issue.

PMID- 27050645
TI  - Identifying Enclosed Chemical Reaction and Dynamics at the Molecular Level Using
      Shell-Isolated Miniaturized Plasmonic Liquid Marble.
AB  - Current microscale tracking of chemical kinetics is limited to destructive ex
      situ methods. Here we utilize Ag nanocube-based plasmonic liquid marble (PLM)
      microreactor for in situ molecular-level identification of reaction dynamics. We
      exploit the ultrasensitive surface-enhanced Raman scattering (SERS) capability
      imparted by the plasmonic shell to unravel the mechanism and kinetics of aryl
      diazonium surface grafting reaction in situ, using just a 2-MUL reaction droplet.
      This reaction is a robust approach to generate covalently functionalized metallic
      surfaces, yet its kinetics remain unknown to date. Experiments and simulations
      jointly uncover a two-step sequential grafting process. An initial Langmuir
      chemisorption of sulfonicbenzene diazonium (dSB) salt onto Ag surfaces forms an
      intermediate sulfonicbenzene monolayer (Ag-SB), followed by subsequent
      autocatalytic multilayer growth of Ag-SB3. Kinetic rate constants reveal 19-fold
      faster chemisorption than multilayer growth. Our ability to precisely decipher
      molecular-level reaction dynamics creates opportunities to develop more efficient
      processes in synthetic chemistry and nanotechnology. 

PMID- 27050646
TI  - Multiplexed Sequence Encoding: A Framework for DNA Communication.
AB  - Synthetic DNA has great propensity for efficiently and stably storing non
      biological information. With DNA writing and reading technologies rapidly
      advancing, new applications for synthetic DNA are emerging in data storage and
      communication. Traditionally, DNA communication has focused on the encoding and
      transfer of complete sets of information. Here, we explore the use of DNA for the
      communication of short messages that are fragmented across multiple distinct DNA
      molecules. We identified three pivotal points in a communication-data encoding,
      data transfer & data extraction-and developed novel tools to enable communication
      via molecules of DNA. To address data encoding, we designed DNA-based
      individualized keyboards (iKeys) to convert plaintext into DNA, while reducing
      the occurrence of DNA homopolymers to improve synthesis and sequencing processes.
      To address data transfer, we implemented a secret-sharing system-Multiplexed
      Sequence Encoding (MuSE)-that conceals messages between multiple distinct DNA
      molecules, requiring a combination key to reveal messages. To address data
      extraction, we achieved the first instance of chromatogram patterning through
      multiplexed sequencing, thereby enabling a new method for data extraction. We
      envision these approaches will enable more widespread communication of
      information via DNA. 

PMID- 27050647
TI  - Cochlear Implant Outcomes in Cochlea Nerve Aplasia and Hypoplasia.
AB  - OBJECTIVE: To assess cochlear implant (CI) outcomes, and factors affecting
      outcomes, for children with aplasia/ hypoplasia of the cochlea nerve. We also
      developed a new grading system for the nerves of the internal auditory meatus
      (IAM) and cochlea nerve classification. STUDY DESIGN: Retrospective patient
      review. SETTING: Tertiary referral hospital and cochlear implant program.
      PATIENTS: Children 0 to 16 years inclusive with a CI who had absent/hypoplastic
      cochlea nerve on magnetic resonance imaging (MRI). INTERVENTION: Cochlear
      implant. MAIN OUTCOME MEASURES: MRI, trans-tympanic electrical auditory brainstem
      response, intraoperative electrical auditory brainstem response, Neural Response
      Telemetry, Categories of Auditory Perception score, Main mode of communication.
      RESULTS: Fifty CI recipients (26 males and 24 females) were identified, 21 had
      bilateral CIs, 27 had developmental delay. MRI showed cochlea nerve aplasia in 64
      ears, hypoplasia in 25 ears, and a normal nerve in 11 ears. Main mode of
      communication was analyzed for 41 children: 21 (51%) used verbal language (15
      speech alone, 5 speech plus some sign, 1 bilingual in speech and sign), and 20
      (49%) used sign language (10 sign alone, 9 sign plus some speech, 1 tactile
      sign). Seventy-three percent of children used some verbal language. Cochlea nerve
      aplasia/ hypoplasia and developmental delay were both significant factors
      affecting main mode of communication. Categories of Auditory Performance scores
      were available for 59 CI ears; 47% with CN Aplasia (IAM nerve grades 0-III) and
      89% with CN hypoplasia (IAM nerve grade IV) achieved Categories of Auditory
      Performance scores of 5 to 7 (some verbal understanding) (p = 0.003). CONCLUSION:
      Our results are encouraging and useful when counselling families regarding the
      likelihood of language outcomes and auditory understanding.

PMID- 27050648
TI  - Patterns of Long-term Hearing Loss in Hearing Preservation Cochlear Implant
      Surgery.
AB  - OBJECTIVE: To describe patterns of hearing loss in patients with low-frequency
      residual hearing after cochlear implantation. STUDY DESIGN: Retrospective chart
      review. SETTING: Tertiary referral center. PATIENTS: Cochlear implant candidates
      with immediate postoperative residual low-frequency hearing. INTERVENTIONS:
      Hybrid or traditional cochlear implant. MAIN OUTCOME MEASURE: Audiograms to
      measure postoperative hearing. RESULTS: Of the 166 patients reviewed, 17 ears met
      the inclusion criteria. The age ranged from 3 years 2 months to 86 years.
      Etiology was unknown (n = 6), presbycusis (n = 5), genetic (n = 4), acoustic
      trauma (n = 1), and measles virus (n = 1). The Nucleus Hybrid S8 and S12 (n = 7)
      was the most common electrode array, and then Nucleus 422 (n = 6), Nucleus
      Contour Advance (n = 2), Med-El Flex 28 (n = 2), and Advanced Bionics Mid Scala
      (n = 1). Cochleostomy was performed in nine, and round window approach in nine
      patients. Average follow-up was 28 months (2-68 mo). Postoperative loss was mixed
      in eight and purely sensorineural in eight. The most common patterns of hearing
      loss were gradual decline (n = 7), and then fluctuating hearing (n = 6), stable
      (n = 3), and sudden loss (n = 1). One patient only had one postoperative
      audiogram. CONCLUSION: Some long-term hearing preservation was achieved in 94% of
      patients with immediate postoperative hearing preservation. Patients developed
      both mixed and sensorineural loss postoperatively. A majority of patients with
      mixed hearing loss had a supra-preoperative bone curve. Gradual decline and
      fluctuating hearing loss were the most common patterns of hearing loss; few
      patients had stable hearing and one had a sudden loss.

PMID- 27050649
TI  - Vascular and Neuroepithelial Histopathology of the Saccule in Humans With
      Diabetes Mellitus.
AB  - HYPOTHESIS: This study aimed to determine if there are quantitative differences
      in the neuroepithelium and microvasculature of the saccule between subjects with
      and without diabetes mellitus (DM). BACKGROUND: Histopathologic changes that may
      underlie the association between DM and vestibular dysfunction have not been
      characterized in humans. METHODS: Human temporal bones (HTBs) from 39 subjects
      with DM (n = 16 type I DM [T1DM], n = 23 type II DM [T2DM]) were compared with 40
      group age-matched controls. Vessel wall thickness was measured from the saccular
      arteriole. Type I and type II vestibular hair cell (VHC) counts were performed on
      perpendicularly oriented saccular maculae using differential interference
      contrast microscopy (T1DM: 5HTB/3 subjects; T2DM: 9HTB/8 subjects; controls:
      25HTB/20 subjects). RESULTS: The mean density of type I VHCs was 16 to 17% lower
      in the DM groups compared to controls (T1DM 52.21 [4.26], T2DM 53.3 [5.34],
      control 63.14 [2.49] cells/mm, p = 0.02). There were no differences between T1DM,
      T2DM, and control groups in type II VHC density (T1DM 40.89 [5.17], T2DM 40.44
      [6.93], control 42.80 [1.79] cells/mm, p = 0.92) or in mean vessel wall thickness
      (T1DM 2.23 [0.62], T2DM 2.18 [0.53], control 2.00 [0.53] MUm, p = 0.26).
      CONCLUSION: Neuroepithelial pathology, manifested as lower density of type I
      VHCs, was observed in the saccules of subjects with DM. Saccular microangiopathy,
      expressed as alterations in arteriole thickness, was not observed. These findings
      are consistent with histologic observations in animals with experimentally
      induced diabetes. DM may have a selective and deleterious effect on human
      vestibular sensory epithelia.

PMID- 27050650
TI  - Cochlear Histopathologic Findings in Patients With Systemic Lupus Erythematosus:
      A Human Temporal Bone Study.
AB  - HYPOTHESIS: We hypothesized that, in archived human temporal bone samples from
      patients with systemic lupus erythematosus (SLE), a pathologic condition exists
      in the stria vascularis and cochlear hair cells. BACKGROUND: Sensorineural
      hearing loss is a common feature in SLE patients. However, the pathophysiologic
      mechanism of cochlear dysfunction is unclear. METHODS: We examined 15 temporal
      bone samples from 8 SLE patients, along with 17 samples from 10 age-matched
      healthy control patients. The samples were serially sectioned in the horizontal
      plane and stained with hematoxylin and eosin. We determined the area of the stria
      vascularis in a midmodiolar section of each cochlear turn. Then, we made
      cytocochleograms and calculated the percentage of missing inner and outer hair
      cells. RESULTS: The area of the stria vascularis in our SLE group was
      significantly smaller than in our control group. The number of remaining inner
      hair cells in our SLE group was smaller than in our control group; however, the
      difference did not reach statistical significance. The loss of outer hair cells
      in our SLE group was significantly higher than in our control group. There was a
      tendency toward a positive correlation between the loss of cochlear hair cells
      and the duration of SLE. CONCLUSION: The stria vascularis and cochlear hair cells
      are affected in SLE patients. Our findings could provide the histopathologic
      basis for the cochlear dysfunction, including sensorineural hearing loss,
      experienced by SLE patients.

PMID- 27050651
TI  - Health-related Quality of Life of Individuals With Neurofibromatosis Type 2:
      Results From the NF2 Natural History Study.
AB  - OBJECTIVE: To explore health-related quality of life (HRQoL) reported by
      individuals with neurofibromatosis type 2 (NF2) and to assess for correlations
      between HRQoL and objective measures of disease manifestations. STUDY DESIGN:
      Prospective observational study. SETTING: Seven international NF2 centers.
      SUBJECTS: Eighty-one individuals with NF2, 73 adults (>18 years) and 8
      children/adolescents (10-17 years). OUTCOME MEASURES: Quality of life was
      measured by Short Form-36 (SF-36) norm-based scores. Objective clinical measures
      were hearing (categorized by word-recognition scores), facial function
      (categorized by the House-Brackmann scale) and the volume of subjects' larger
      vestibular schwannoma (VS). RESULTS: At baseline, adults showed significant
      deficits in all but two subscales of the SF-36 compared with age- and gender
      adjusted United States population norms. In linear regression models including
      age, gender, inheritance status, hearing, facial weakness and VS volume,
      demographic and functional measures showed no relationship to any SF-36 subscale.
      Larger baseline VS volume was significantly related to reduced physical role
      performance, reduced mental health, and increased pain (p < 0.05). In bivariate
      analysis, previous VS surgery was not significantly associated with baseline
      HRQoL; receipt of VS surgery or tumor growth during the observation period was
      not significantly associated with changes in HRQoL. CONCLUSION: NF2 patients
      report reduced HRQoL in physical, social, and mental domains, but this was not
      significantly related to objective measures of hearing or facial functioning.
      Larger baseline VS volume negatively impacted patient-reported HRQoL whereas VS
      surgery or tumor growth did not. Future studies should explore the relationship
      between tumor volume and HRQoL and psychosocial factors that may moderate this
      relationship.

PMID- 27050652
TI  - Click Stimulus Electrocochleography Versus MRI With Intratympanic Contrast in
      Meniere's Disease: A Systematic Review.
AB  - OBJECTIVE: To evaluate the diagnostic value of electrocochleography compared with
      magnetic resonance imaging (MRI) with intratympanic gadolinium administration to
      diagnose endolymphatic hydrops in patients with Meniere's disease. DATA SOURCES:
      An electronic search was performed in the PubMed, EMBASE, and Cochrane databases
      on September 15, 2015. A systematic search was conducted. Articles were included
      if written in English, Dutch, German, or French language. STUDY SELECTION:
      Original studies reporting on the diagnostic value of electrocochleography
      compared with MRI with intratympanic gadolinium administration, were included.
      DATA EXTRACTION: The methodological quality of the studies was independently
      assessed by two reviewers using an adjusted version of the Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS) tool. The results of the diagnostic values
      of both tests were extracted. DATA SYNTHESIS: We performed analyses for the
      sensitivity, specificity, positive predictive value, and negative predictive
      value of compared electrocochleography with MRI with intratympanic gadolinium
      administration in patients with definite Meniere's disease. CONCLUSION: The
      results of this systematic review, based on a very low number of patients, show
      there is a relative low sensitivity and negative predictive value for click
      stimulus electrocochleography compared with MRI with intratympanic gadolinium
      administration for detecting endolymphatic hydrops in patients with definite
      Meniere's disease.

PMID- 27050654
TI  - Diffusion-weighted Magnetic Resonance Imaging as a Novel Imaging Modality in
      Assessing Treatment Response in Necrotizing Otitis Externa.
AB  - OBJECTIVE: To report our initial experience of diffusion-weighted magnetic
      resonance imaging (DW-MRI) as a novel imaging tool for assessing and monitoring
      treatment response in necrotizing otitis externa (NOE). PATIENTS: Seven adults
      with a diagnosis of NOE on both clinical and computed tomography (CT) criteria
      who were subsequently monitored with at least two echoplanar DW-MRI
      investigations were included in this retrospective longitudinal observational
      study. INTERVENTION: Patients underwent magnetic resonance imaging (MRI),
      including echoplanar diffusion-weighted sequences, within 2 weeks of diagnosis of
      NOE to determine the extent of infection and to provide a baseline scan for
      monitoring response to treatment. Repeated imaging was undertaken after the
      agreed initial course of antimicrobial therapy was completed. MAIN OUTCOME
      MEASURE: The primary outcome measure for complete treatment response was complete
      resolution of high inflammatory signal on the DW-MRI apparent diffusion
      coefficient (ADC) map. This was correlated to clinical, biochemical, and other
      MRI measures of disease resolution. RESULTS: Baseline DW-MRI was carried out in
      all but one patient within 2 weeks of the initial diagnostic CT scan. Patients
      had between one and three further DW-MRI scans, at a mean interval of 4.4 months
      from the initial scan (range, 2-8 months). The decision to terminate or continue
      therapy correlated with ADC signal findings on DW-MRI in all cases. In
      comparison, conventional MRI sequences performed less well, as there was some
      degree of persistent residual soft tissue changes in all cases.

PMID- 27050653
TI  - Craniocervical Pneumatization: Estimation of Prevalence and Imaging of Treatment
      Response.
AB  - OBJECTIVE: Estimate the prevalence of craniocervical pneumatization (CCP) and
      describe successful treatment of this condition with clinical and radiologic
      correlation. PATIENTS: Individuals with documented CCP on computed tomography
      (CT). INTERVENTION(S): CT scans of the head, temporal bone, face, neck, and
      cervical spine. Cessation of habitual Valsalva maneuver (VM) and insertion of
      pressure-equalization (PE) tubes. MAIN OUTCOME MEASURE: The prevalence of CCP on
      CT examinations performed during two decades in a large academic healthcare
      system. Documentation of symptomatic and imaging improvement following treatment
      of CCP. RESULTS: Radiology database review identified two cases of CCP out of a
      total of 636,854 head and neck CT scans (0.00031%) or 43,553 temporal bone CT
      scans (0.0046%). Both CCP patients were symptomatic (aural fullness, hearing
      loss, vertigo) and practiced habitual VM. One patient showed decreased CCP 4
      months following cessation of VM, whereas the other patient improved
      symptomatically and demonstrated reversion of CCP to normal bone on magnetic
      resonance imaging (MRI) within 3 years following PE tube placement. CONCLUSIONS:
      Acquired CCP is exceedingly rare and, when successfully treated, reversion to
      normal bone may accompany symptom resolution.

PMID- 27050655
TI  - Effect of Round Window Reinforcement on Hearing: A Temporal Bone Study With
      Clinical Implications for Surgical Reinforcement of the Round Window.
AB  - HYPOTHESIS: Round window reinforcement leads to conductive hearing loss.
      BACKGROUND: The round window is stiffened surgically as therapy for various
      conditions, including perilymphatic fistula and superior semicircular canal
      dehiscence. Round window reinforcement reduces symptoms in these patients.
      However, it also reduces fluid displacement in the cochlea and might therefore
      increase conductive hearing loss. METHODS: Perichondrium was applied to the round
      window membrane in nine fresh-frozen, nonpathologic temporal bones. In four
      temporal bones cartilage was applied subsequently. Acoustic stimuli in the form
      of frequency sweeps from 250 to 8000 Hz were generated at 110 dB sound pressure
      level. A total of 16 frequencies in a 1/3-octave series were used. Stapes
      velocities in response to the acoustic stimuli were measured at equally spaced
      multiple points covering the stapes footplate using a scanning laser Doppler
      interferometry system. Measurements were made at baseline, after applying
      perichondrium, and after applying cartilage. RESULTS: At frequencies up to 1000
      Hz perichondrium reinforcement decreased stapes velocities by 1.5 to 2.9 dB
      compared with no reinforcement (p value = 0.003). Reinforcement with cartilage
      led to a further deterioration of stapes velocities by 2.6 to 4.2 dB at
      frequencies up to 1000 Hz (p value = 0.050). The higher frequencies were not
      affected by perichondrium reinforcement (p value = 0.774) or cartilage
      reinforcement (p value = 0.644). CONCLUSION: Our results seem to suggest a
      modest, clinically negligible effect of reinforcement with perichondrium. Placing
      cartilage on the round window resulted in a graded effect on stapes velocities in
      keeping with the increased stiffness of cartilage compared with perichondrium.
      Even so, the effect was relatively small.

PMID- 27050656
TI  - Clinical suspicion, management and outcome of intrapartum foetal distress in a
      public hospital with limited advanced foetal surveillance.
AB  - OBJECTIVES: To determine the basis for the clinical suspicion of foetal distress,
      the instituted managements and delivery outcome in a tertiary hospital in sub
      Saharan Africa with limited capability for advanced foetal monitoring. METHODS:
      It is a 3-year retrospective analysis of all the obstetrics cases with
      intrapartum foetal distress. RESULTS: There were 301 cases reviewed. The birth
      asphyxia incidence rate was 233/1000 live births and the perinatal death rate was
      47/1000 live births. Suspicion of foetal distress was premised on the presence of
      persistent tachycardia or bradycardia during intermittent auscultation. Main
      resuscitative measures were left lateral repositioning of patient, fast saline
      infusion, intranasal oxygen administration and discontinuation of oxytocin
      infusion, if any. Only 124 (41.2%) of all the cases had delivery achieved within
      2 h of diagnosis. Mean decision-delivery interval by caesarean section was 2.93
      +/- 2.05 h. Socio-demographic factors (p= 0.001) and pregnancy risk category (p =
      0.002) influenced incidence of birth asphyxia. CONCLUSION: To reduce subsisting
      high perinatal morbidity and mortality in sub-Saharan Africa, it is best that at
      the least referral hospitals should have advanced facilities for foetal
      monitoring and shortened surgical intervention time.

PMID- 27050657
TI  - Cytotoxic pimarane-type diterpenes from the marine sediment-derived fungus
      Eutypella sp. FS46.
AB  - Two new pimarane-type diterpenes, scopararanes H-I (1-2), along with five known
      ones (3-7) were isolated from the culture broth of a marine sediment-derived
      fungus Eutypella sp. FS46, which was obtained from the South China Sea. Their
      structures were established by extensive spectroscopic analysis. All of them were
      evaluated for their cytotoxic activities against MCF-7, NCI-H460 and SF-268
      tumour cell lines. Scopararane I (2) showed moderate inhibitory activities.

PMID- 27050658
TI  - Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small
      Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada) Region.
AB  - Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine-
      operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3)
      dust, among other compounds, from gold ore extraction and roasting processes. For
      the first time, we show the geospatial distribution of roaster-derived emissions
      of several chemical species beyond the mine property on otherwise undisturbed
      taiga shield lakes within a 25 km radius of the mine, 11 years after its closing.
      Additionally, we demonstrate that underlying bedrock is not a significant source
      for the elevated concentrations in overlying surface waters. Aquatic arsenic (As)
      concentrations are well above guidelines for drinking water (10 MUg/L) and
      protection for aquatic life (5 MUg/L), ranging up to 136 MUg/L in lakes within 4
      km from the mine, to 2.0 MUg/L in lakes 24 km away. High conversion ratios of
      methyl mercury were shown in lakes near the roaster stack as well, with MeHg
      concentrations reaching 44% of total mercury. The risk of elevated exposures by
      these metals is significant, as many lakes used for recreation and fishing near
      the City of Yellowknife are within this radius of elevated As and methyl Hg
      concentrations.

PMID- 27050659
TI  - How Much Is the Dose Varying between Follow-Up CT-Examinations Performed on the
      Same Scanner with the Same Imaging Protocol?
AB  - PURPOSE: To investigate the dose variation between follow-up CT examinations,
      when a patient is examined several times on the same scanner with the identical
      scan protocol which comprised automated exposure control. MATERIAL AND METHODS:
      This retrospective study was approved by the local ethics committee. The volume
      computed tomography dose index (CTDIvol) and the dose-length-product (DLP) were
      recorded for 60 cancer patients (29 male, 31 female, mean age 60.1 years), who
      received 3 follow-up CT examinations each composed of a non-enhanced scan of the
      liver (LI-CT) and a contrast-enhanced scan of chest (CH-CT) and abdomen (AB-CT).
      Each examination was performed on the same scanner (Siemens Definition FLASH)
      equipped with automated exposure control (CARE Dose 4D and CARE KV) using the
      identical scan protocol. RESULTS: The median percentage difference in DLP between
      follow-up examinations was 9.6% for CH-CT, 10.3% for LI-CT, and 10.1% for AB-CT;
      the median percentage difference in CTDIvol 8.3% for CH-CT, 7.4% for LI-CT and
      7.7% for AB-CT (p<0.0001 for all values). The maximum difference in DLP between
      follow-up examinations was 67.5% for CH-CT, 50.8% for LI-CT and 74.3% for AB-CT;
      the maximum difference in CTDIvol 62.9% for CH-CT, 47.2% for LI-CT, and 49% for
      AB-CT. CONCLUSION: A significant variance in the radiation dose occurs between
      follow-up CT examinations when the same CT scanner and the identical imaging
      protocol are used in combination with automated exposure control.

PMID- 27050660
TI  - Single cell rigidity sensing: A complex relationship between focal adhesion
      dynamics and large-scale actin cytoskeleton remodeling.
AB  - Many physiological and pathological processes involve tissue cells sensing the
      rigidity of their environment. In general, tissue cells have been shown to react
      to the stiffness of their environment by regulating their level of contractility,
      and in turn applying traction forces on their environment to probe it. This
      mechanosensitive process can direct early cell adhesion, cell migration and even
      cell differentiation. These processes require the integration of signals over
      time and multiple length scales. Multiple strategies have been developed to
      understand force- and rigidity-sensing mechanisms and much effort has been
      concentrated on the study of cell adhesion complexes, such as focal adhesions,
      and cell cytoskeletons. Here, we review the major biophysical methods used for
      measuring cell-traction forces as well as the mechanosensitive processes that
      drive cellular responses to matrix rigidity on 2-dimensional substrates.

PMID- 27050661
TI  - Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication.
AB  - The uptake of microfluidics by the wider scientific community has been limited by
      the fabrication barrier created by the skills and equipment required for the
      production of traditional microfluidic devices. Here we present simple 3D printed
      microfluidic devices using an inexpensive and readily accessible printer with
      commercially available printer materials. We demonstrate that previously reported
      limitations of transparency and fidelity have been overcome, whilst devices
      capable of operating at pressures in excess of 2000 kPa illustrate that leakage
      issues have also been resolved. The utility of the 3D printed microfluidic
      devices is illustrated by encapsulating dental pulp stem cells within alginate
      droplets; cell viability assays show the vast majority of cells remain live, and
      device transparency is sufficient for single cell imaging. The accessibility of
      these devices is further enhanced through fabrication of integrated ports and by
      the introduction of a Lego(r)-like modular system facilitating rapid prototyping
      whilst offering the potential for novices to build microfluidic systems from a
      database of microfluidic components. 

PMID- 27050662
TI  - Does nonlinear resistance training reduce metabolic syndrome in people living
      with HIV? A randomized clinical trial.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of a 12-week
      nonlinear resistance training (NLRT) program on metabolic syndrome (MetS)
      components in people living with human immunodeficiency virus (PLHIV) and
      diagnosed with MetS. METHODS: Subjects were randomly assigned to either a NLRT
      (N.=10) or control (CON; N.=11) group. The NLRT group exercised three times per
      week during the 12 week supervised training program. The CON group was asked to
      maintain their daily habits. At baseline (pre) and after the intervention (post),
      both groups completed anthropometric, blood pressure, and biochemical
      assessments. A 2x2 repeated measures ANOVA (significance level of 5%) was
      performed to calculate the effects of intervention duration (time), group, and
      the interaction between the two. RESULTS: There was a significant time*group
      interaction for lean body mass (LBM) (+5.5%, P<0.0001), body fat mass (BFM) (
      10.1%, P<0.0001), body fat percentage (BF%) (-11.4%, P<0.0001), waist
      circumference (WC) (-1%, P=0.001), high-density lipoprotein (HDL) (+31%,
      P<0.0001) levels, fasting glucose (FG) (-13.7%, P=0.012), and glycated hemoglobin
      (HBA1C) (-9%, P<0.0001). After the intervention, the NLRT group included fewer
      participants with abnormal levels of triglycerides (TG), HDL, systolic blood
      pressure (SBP), diastolic blood pressure (DBP), and FG while the CON group had
      more participants with abnormal levels of TG, SBP, and DBP. CONCLUSIONS: Twelve
      weeks of NLRT was effective in ameliorating some components of MetS in PLHIV.

PMID- 27050663
TI  - Undergraduate Nursing Students' Evaluation of the Debriefing Phase in Mental
      Health Nursing Simulation.
AB  - The debriefing phase in mental health nursing simulation promotes a reflexive
      learning process with the opportunity to develop metacognitive and nontechnical
      skills. The aim of this quantitative study was to describe undergraduate nursing
      students' evaluation of their experience during the debriefing phase following
      high fidelity human simulation (HFHS). Data was collected using the "Debriefing
      Experience Scale" and analysed with descriptive and comparative tests. The
      debriefing phase was evaluated as very good. Background data and group size
      revealed few significant differences. Students with little clinical praxis
      evaluated having time to acknowledge feelings as important. Differences between
      groups revealed that groups should consist of up to eighteen students. 

PMID- 27050664
TI  - Barriers to home-based exercise program adherence with chronic low back pain:
      Patient expectations regarding new technologies.
AB  - OBJECTIVE: To assess views of patients with chronic low back pain (cLBP)
      concerning barriers to home-based exercise program adherence and to record
      expectations regarding new technologies. DESIGN: Qualitative study based on semi
      structured interviews. PARTICIPANTS: A heterogeneous sample of 29 patients who
      performed a home-based exercise program for cLBP learned during supervised
      physiotherapy sessions in a tertiary care hospital. INTERVENTIONS: Patients were
      interviewed at home by the same trained interviewer. Interviews combined a funnel
      shaped structure and an itinerary method. RESULTS: Barriers to adherence related
      to the exercise program (number, effectiveness, complexity and burden of
      exercises), the healthcare journey (breakdown between supervised sessions and
      home exercise, lack of follow-up and difficulties in contacting care providers),
      patient representations (illness and exercise perception, despondency, depression
      and lack of motivation), and the environment (attitudes of others, difficulties
      in planning exercise practice). Adherence could be enhanced by increasing the
      attractiveness of exercise programs, improving patient performance (following a
      model or providing feedback), and the feeling of being supported by care
      providers and other patients. Regarding new technologies, relatively younger
      patients favored visual and dynamic support that provided an enjoyable and
      challenging environment and feedback on their performance. Relatively older
      patients favored the possibility of being guided when doing exercises. Whatever
      the tool proposed, patients expected its use to be learned during a supervised
      session and performance regularly checked by care providers; they expected
      adherence to be discussed with care providers. CONCLUSIONS: For patients with
      cLBP, adherence to home-based exercise programs could be facilitated by
      increasing the attractiveness of the programs, improving patient performance and
      favoring a feeling of being supported. New technologies meet these challenges and
      seem attractive to patients but are not a substitute for the human relationship
      between patients and care providers.

PMID- 27050665
TI  - Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species
      and Inhibits Colon Cancer.
AB  - Massively increasing global incidences of colorectal cancer require efficient
      treatment and prevention strategies. Here, we report unexpected anticancerogenic
      effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely
      used phytomedical product for treating gastrointestinal complaints. IAE
      significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells
      with an inhibitory concentration (IC50) of 6 and 9 MUg/ml, respectively, and
      further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer
      cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M
      phase cell cycle arrest including reduced expression of various regulatory marker
      proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular
      formation of reactive oxygen species (ROS). Consistent with predictions derived
      from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4
      weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor
      xenograft model. Taken together, Iberis amara extracts could become useful
      alternatives for preventing and treating the progression of colon cancer. 

PMID- 27050666
TI  - The refusal of the Society to accept antibiotic toxicity: missing opportunities
      for therapy of severe infections.
AB  - Over the last decade the emergence and spread of antibiotic resistance in
      bacteria has led to a new fear in the scientific and medical communities as well
      as among members of the general public. Due to the lack of development of new
      antibiotics, there is a need to reconsider old drugs or dosages rejected because
      of their toxicity. As a society, if we tolerate the potential toxicity of other
      drugs, such as anticancer drugs, why do we refuse to accept the use of toxic but
      effective antibiotics in life-threatening infections? The aim of this review is
      to provide insight into the reasons why the medical community remains
      unjustifiably unwilling to accept the risk of toxicity and the adverse effects of
      antibiotics that, nonetheless, might be required to treat severe infections,
      including those due to multidrug-resistant bacteria. 

PMID- 27050667
TI  - Lowering methodological standards for studies of multidrug-resistant bacteria is
      counterproductive.

PMID- 27050668
TI  - The accuracy of preoperative axillary nodal staging in primary breast cancer by
      ultrasound is modified by nodal metastatic load and tumor biology.
AB  - Background The outcome of axillary ultrasound (AUS) with fine-needle aspiration
      biopsy (FNAB) in the diagnostic work-up of primary breast cancer has an impact on
      therapy decisions. We hypothesize that the accuracy of AUS is modified by nodal
      metastatic burden and clinico-pathological characteristics. Material and methods
      The performance of AUS and AUS-guided FNAB for predicting nodal metastases was
      assessed in a prospective breast cancer cohort subjected for surgery during 2009
      2012. Predictors of accuracy were included in multivariate analysis. Results AUS
      had a sensitivity of 23% and a specificity of 95%, while AUS-guided FNAB obtained
      73% and 100%, respectively. AUS-FNAB exclusively detected macro-metastases
      (median four metastases) and identified patients with more extensive nodal
      metastatic burden in comparison with sentinel node biopsy. The accuracy of AUS
      was affected by metastatic size (OR 1.11), obesity (OR 2.46), histological grade
      (OR 4.43), and HER2-status (OR 3.66); metastatic size and histological grade were
      significant in the multivariate analysis. Conclusions The clinical utility of AUS
      in low-risk breast cancer deserves further evaluation as the accuracy decreased
      with a low nodal metastatic burden. The diagnostic performance is modified by
      tumor and clinical characteristics. Patients with nodal disease detected by AUS
      FNAB represent a group for whom neoadjuvant therapy should be considered. 

PMID- 27050670
TI  - The Social Construction of Inflammatory Bowel Disease Using Social Media
      Technologies.
AB  - Many people with inflammatory bowel disease (IBD), sometimes lacking adequate
      face-to-face sources of support, turn to online communities to meet others with
      the disease. These online communities are places of support and education, but
      through the use of social media communication technologies, people with IBD are
      redefining what it means to live with the disease. This ethnographic study
      followed 14 online communities to understand how people with IBD used social
      media technologies to construct their own meanings about living with the disease.
      The following redefinitions were observed: the refiguring of the body is
      beautiful; inflammatory bowel disease is serious and deadly; inflammatory bowel
      disease is humorous; the disease makes one stronger; and the disease is
      invisible, but needs to be made visible. This study will help health
      communication scholars understand how technology is appropriated by patients, and
      will help practitioners understand how their patients conceptualize their
      disease.

PMID- 27050669
TI  - Immune Checkpoint Blockade to Improve Tumor Infiltrating Lymphocytes for Adoptive
      Cell Therapy.
AB  - Tumor-infiltrating lymphocytes (TIL) has been associated with improved survival
      in cancer patients. Within the tumor microenvironment, regulatory cells and
      expression of co-inhibitory immune checkpoint molecules can lead to the
      inactivation of TIL. Hence, there is a need to develop strategies that disrupt
      these negative regulators to achieve robust anti-tumor immune responses. We
      evaluated the blockade of immune checkpoints and their effect on T cell
      infiltration and function. We examined the ability of TIL to induce tumor
      specific immune responses in vitro and in vivo. TIL isolated from tumor bearing
      mice were tumor-specific and expressed co-inhibitory immune checkpoint molecules.
      Administration of monoclonal antibodies against immune checkpoints led to a
      significant delay in tumor growth. However, anti-PD-L1 antibody treated mice had
      a significant increase in T cell infiltration and IFN-gamma production compared
      to other groups. Adoptive transfer of in vitro expanded TIL from tumors of anti
      PD-L1 antibody treated mice led to a significant delay in tumor growth. Blockade
      of co-inhibitory immune checkpoints could be an effective strategy to improve TIL
      infiltration and function. 

PMID- 27050671
TI  - "May I Buy a Pack of Marlboros, Please?" A Systematic Review of Evidence to
      Improve the Validity and Impact of Youth Undercover Buy Inspections.
AB  - Most smokers become addicted to tobacco products before they are legally able to
      purchase these products. We systematically reviewed the literature on protocols
      to assess underage purchase and their ecological validity. We conducted a
      systematic search in May 2015 in PubMed and PsycINFO. We independently screened
      records for inclusion. We conducted a narrative review and examined implications
      of two types of legal authority for protocols that govern underage buy
      enforcement in the United States: criminal (state-level laws prohibiting sales to
      youth) and administrative (federal regulations prohibiting sales to youth). Ten
      studies experimentally assessed underage buy protocols and 44 studies assessed
      the association between youth characteristics and tobacco sales. Protocols that
      mimicked real-world youth behaviors were consistently associated with
      substantially greater likelihood of a sale to a youth. Many of the tested
      protocols appear to be designed for compliance with criminal law rather than
      administrative enforcement in ways that limited ecological validity. This may be
      due to concerns about entrapment. For administrative enforcement in particular,
      entrapment may be less of an issue than commonly thought. Commonly used underage
      buy protocols poorly represent the reality of youths' access to tobacco from
      retailers. Compliance check programs should allow youth to present themselves
      naturally and attempt to match the community's demographic makeup. 

PMID- 27050672
TI  - The EULAR Sjogren's Syndrome Patient-Reported Index is an independent determinant
      of health-related utility values of Korean patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVES: This study was undertaken to evaluate the health-related quality of
      life (HRQoL) in patients with primary Sjogren's syndrome (pSS) and to identify
      its predictors among various clinical parameters. METHODS: The EuroQoL-5
      dimension (EQ-5D) was used to measure the patients' HRQoL. The utility values of
      178 patients with pSS enrolled in a prospective pSS cohort in Korea were analysed
      and compared with the Korean normative data. The associations among the clinical
      parameters and utility values were evaluated. RESULTS: The mean utility value of
      the pSS patients was significantly lower than that of the Korean general
      population (0.773+/-0.138 vs. 0.944+/-0.095, p<0.001). The proportion of patients
      with problems in the 4 dimensions was significantly higher in the pSS patients
      than in the general population (anxiety/depression 70.2 vs. 24.2%, pain 78.7 vs.
      28.8%, usual activities 37.6 vs. 9.8%, and mobility 40.4 vs. 12.5%, p<0.001).
      Bivariate correlation analyses revealed that the degree of pain, fatigue, and
      patient global assessment of the disease was positively correlated with the
      utility value. The xerostomia inventory score, ocular surface disease index, and
      the EULAR Sjogren's syndrome patient-reported index (ESSPRI) also correlated with
      the utility value. On multiple regression analysis, only the ESSPRI remained in
      the model after stepwise selection adjusted for age and sex (coefficient beta =
      0.053, p<0.001). CONCLUSIONS: The HRQoL of pSS patients is significantly lower
      than that of the general population, and the ESSPRI is an independent predictor
      of the HRQoL in pSS patients.

PMID- 27050673
TI  - Flocculated meltwater particles control Arctic land-sea fluxes of labile iron.
AB  - Glacial meltwater systems supply the Arctic coastal ocean with large volumes of
      sediment and potentially bioavailable forms of iron, nitrogen and carbon. The
      particulate fraction of this supply is significant but estuarine losses have been
      thought to limit the iron supply from land. Here, our results reveal how
      flocculation (particle aggregation) involving labile iron may increase horizontal
      transport rather than enhance deposition close to the source. This is shown by
      combining field observations in Disko Fjord, West Greenland, and laboratory
      experiments. Our data show how labile iron affects floc sizes, shapes and
      densities and consequently yields low settling velocities and extended sediment
      plumes. We highlight the importance of understanding the flocculation mechanisms
      when examining fluxes of meltwater transported iron in polar regions today and in
      the future, and we underline the influence of terrestrial hotspots on the
      nutrient and solute cycles in Arctic coastal waters. 

PMID- 27050674
TI  - Correction to NHC Copper(I) Complexes Bearing Dipyridylamine Ligands: Synthesis,
      Structural, and Photoluminescent Studies.

PMID- 27050675
TI  - A Simple and Fast Semiautomatic Procedure for the Atomistic Modeling of Complex
      DNA Polyhedra.
AB  - A semiautomatic procedure to build complex atomistic covalently linked DNA
      nanocages has been implemented in a user-friendly, free, and fast program. As a
      test set, seven different truncated DNA polyhedra, composed by B-DNA double
      helices connected through short single-stranded linkers, have been generated. The
      atomistic structures, including a tetrahedron, a cube, an octahedron, a
      dodecahedron, a triangular prism, a pentagonal prism, and a hexagonal prism, have
      been probed through classical molecular dynamics and analyzed to evaluate their
      structural and dynamical properties and to highlight possible building faults.
      The analysis of the simulated trajectories also allows us to investigate the role
      of the different geometries in defining nanocages stability and flexibility. The
      data indicate that the cages are stable and that their structural and dynamical
      parameters measured along the trajectories are slightly affected by the different
      geometries. These results demonstrate that the constraints imposed by the
      covalent links induce an almost identical conformational variability
      independently of the three-dimensional geometry and that the program presented
      here is a reliable and valid tool to engineer DNA nanostructures.

PMID- 27050676
TI  - Peripheral Arterial Disease in Sub-Saharan Africa: A Review.
AB  - IMPORTANCE: Peripheral arterial disease (PAD) causes significant morbidity and is
      an important risk factor for cardiovascular disease-related mortality. However,
      the burden of PAD in sub-Saharan Africa is poorly understood. OBJECTIVE: To
      assess epidemiological and clinical reports regarding PAD from sub-Saharan Africa
      such that the regional epidemiology and management of PAD could be described and
      recommendations offered. EVIDENCE REVIEW: A systematic search in PubMed, Medline,
      Embase, the Cumulative Index to Nursing and Allied Health Literature, and Google
      Scholar for reports pertaining to the epidemiology and/or management of PAD in
      sub-Saharan Africa was performed. Reports that met inclusion criteria were sorted
      into 3 categories: population epidemiology, clinical epidemiology, and surgical
      case series. Findings were extracted and described. FINDINGS: The search returned
      724 records; of these, 16 reports met inclusion criteria. Peripheral arterial
      disease epidemiology and/or management was reported from 10 of the 48 sub-Saharan
      African countries. Peripheral arterial disease prevalence ranged from 3.1% to 24%
      of adults aged 50 years and older and 39% to 52% of individuals with known risk
      factors (eg, diabetes). Medical management was only described by 2 reports; both
      documented significant undertreatment of PAD as a cardiovascular disease risk
      factor. Five surgical case series reported that trauma and diabetes-related
      complications were the most common indications for vascular surgery. CONCLUSIONS
      AND RELEVANCE: The prevalence of PAD in sub-Saharan Africa may be equal to or
      higher than that in high-income countries, exceeding 50% in some high-risk
      populations. In addition to population-based studies that better define the PAD
      burden in sub-Saharan Africa, health systems should consider studies and action
      regarding risk factor mitigation, targeted screening, medical management of PAD,
      and defining essential vascular care.

PMID- 27050678
TI  - Persistent organic pollutants (POPs) in populations of the clam Chione
      californiensis in coastal lagoons of the Gulf of California.
AB  - This study examines the potential public health risk due to the massive use of
      organochlorine pesticides (OCs) in agriculture in the Gulf of California.
      Specimens of the clam Chione californiensis were collected from three coastal
      lagoons (Yavaros, Altata and Reforma). Sites were classified as
      polluted/nonpolluted based on the presence/absence of OCs as an indicator of the
      persistence of these pollutants; in polluted sites, the time elapsed since
      pesticide application (past or recent) was estimated. Screening values (SV) for
      protecting human health as per the U.S. Environmental Protection Agency (EPA)
      were used for risk assessment. OCs detected were ranked according to frequency of
      occurrence as follows: gamma-chlordane (75%) > endrin (54%) > aldrin (48%) >
      heptachlor, and dichlorodiphenyl-trichloroethane (DDE) (37%) > beta-heptachlor
      epoxide (30%) > lindane (alpha-BHC, delta-BHC) and endosulphan I (<= 6%).
      Specifically, OCs detected at the highest concentration were heptachlor in
      Yavaros (0.0168 ugg(-1)) and Altata (0.0046 ugg(-1)), and aldrin in Reforma
      (0.0019 ugg(-1)). beta-Heptachlor epoxide in Altata and Reforma was the only OC
      with a concentration exceeding the EPA Screening Value. From our results and
      based on the monthly consumption limit set forth by EPA, the maximum safe
      consumption of clams to avoid a carcinogenic risk derived from beta-heptachlor
      epoxide in the fishing villages of Yavaros and Altata is 4 servings per month (1
      serving = 0.227 kg) by a 70-kg person. These findings suggest that concentrations
      of OCs and their isomers in C. californiensis populations reflect environmental
      persistence as well as recent inputs of OCs into coastal lagoons in the Gulf of
      California. 

PMID- 27050679
TI  - Reconstruction of a Lower Conchal Bowl Defect.

PMID- 27050677
TI  - Small molecules, big targets: drug discovery faces the protein-protein
      interaction challenge.
AB  - Protein-protein interactions (PPIs) are of pivotal importance in the regulation
      of biological systems and are consequently implicated in the development of
      disease states. Recent work has begun to show that, with the right tools, certain
      classes of PPI can yield to the efforts of medicinal chemists to develop
      inhibitors, and the first PPI inhibitors have reached clinical development. In
      this Review, we describe the research leading to these breakthroughs and
      highlight the existence of groups of structurally related PPIs within the PPI
      target class. For each of these groups, we use examples of successful discovery
      efforts to illustrate the research strategies that have proved most useful.

PMID- 27050680
TI  - Repair of a Large Heminasal Defect.

PMID- 27050681
TI  - Modified Approach for Repair of Nasal Defects.

PMID- 27050682
TI  - Repair of a Complex Forehead Defect Involving the Brow.

PMID- 27050683
TI  - Exposing the Molecular Machinery of BK Polyomavirus.
AB  - BK polyomavirus (BKV) is an opportunistic pathogen that poses a serious threat to
      organ transplant recipients. In this issue of Structure, Hurdiss and colleagues'
      (Hurdiss et al., 2016) beautiful new high-resolution cryo-EM reconstruction of
      BKV provides a structural roadmap for the ongoing development of therapeutic
      antibodies and vaccines targeting this potentially deadly virus. The study also
      serves as a platform for exploring the basic biology of virion assembly and
      infectious entry.

PMID- 27050684
TI  - Turning a Negative into a Positive: Conversion of a Homodimer into a Heterodimer
      Using Negative State Repertoires.
AB  - In this issue of Structure, Leaver-Fay et al. (2016) engineer bispecific
      antibodies using multistate computational protein design with negative state
      repertoires. In combination with additional mutations selected rationally, they
      produced antibodies that assembled as heterodimers with up to 93% purity.

PMID- 27050685
TI  - Unveiling the Structural and Dynamic Nature of the Ubiquitin Code.
AB  - In this issue of Structure, Castaneda et al. (2016b) use multi-disciplinary
      approaches including NMR techniques, small-angle neutron scattering, and docking
      to convincingly demonstrate that K27-linked diubiquitin is relatively rigid with
      unexpected similarity to the conformation of K48-linked diubiquitin bound to the
      UBA2 domain of hHR23a.

PMID- 27050686
TI  - Acoustic Injectors Meet X-Ray Free-Electron Lasers.
AB  - In this issue of Structure, Roessler et al. (2016) present a new method to
      acoustically inject samples for serial femtosecond crystallography into the focus
      of free-electron lasers. This method can drastically reduce the sample
      consumption of this method. It will therefore play an important role in the mix
      of sample preparation technologies.

PMID- 27050687
TI  - Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop.
AB  - Crystallographic studies of ligands bound to biological macromolecules (proteins
      and nucleic acids) represent an important source of information concerning drug
      target interactions, providing atomic level insights into the physical chemistry
      of complex formation between macromolecules and ligands. Of the more than 115,000
      entries extant in the Protein Data Bank (PDB) archive, ~75% include at least one
      non-polymeric ligand. Ligand geometrical and stereochemical quality, the
      suitability of ligand models for in silico drug discovery and design, and the
      goodness-of-fit of ligand models to electron-density maps vary widely across the
      archive. We describe the proceedings and conclusions from the first Worldwide
      PDB/Cambridge Crystallographic Data Center/Drug Design Data Resource
      (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory
      for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts
      in protein crystallography from academe and industry came together with non
      profit and for-profit software providers for crystallography and with experts in
      computational chemistry and data archiving to discuss and make recommendations on
      best practices, as framed by a series of questions central to structural studies
      of macromolecule-ligand complexes. What data concerning bound ligands should be
      archived in the PDB? How should the ligands be best represented? How should
      structural models of macromolecule-ligand complexes be validated? What
      supplementary information should accompany publications of structural studies of
      biological macromolecules? Consensus recommendations on best practices developed
      in response to each of these questions are provided, together with some details
      regarding implementation. Important issues addressed but not resolved at the
      workshop are also enumerated. 

PMID- 27050689
TI  - Crystal Structure of the Vanadate-Inhibited Ca(2+)-ATPase.
AB  - Vanadate is the hallmark inhibitor of the P-type ATPase family; however,
      structural details of its inhibitory mechanism have remained unresolved. We have
      determined the crystal structure of sarcoplasmic reticulum Ca(2+)-ATPase with
      bound vanadate in the absence of Ca(2+). Vanadate is bound at the catalytic site
      as a planar VO3(-) in complex with water and Mg(2+) in a dephosphorylation
      transition-state-like conformation. Validating bound VO3(-) by anomalous
      difference Fourier maps using long-wavelength data we also identify a hitherto
      undescribed Cl(-) site near the dephosphorylation site. Crystallization was
      facilitated by trinitrophenyl (TNP)-derivatized nucleotides that bind with the
      TNP moiety occupying the binding pocket that normally accommodates the adenine of
      ATP, rationalizing their remarkably high affinity for E2P-like conformations of
      the Ca(2+)-ATPase. A comparison of the configurations of bound nucleotide analogs
      in the E2.VO3(-) structure with that in E2.BeF3(-) (E2P ground state analog)
      reveals multiple binding modes to the Ca(2+)-ATPase.

PMID- 27050690
TI  - Structural Analysis of the Phenol-Responsive Sensory Domain of the Transcription
      Activator PoxR.
AB  - Positive phenol-degradative gene regulator (PoxR) is a sigma(54)-dependent AAA+
      ATPase transcription activator that regulates the catabolism of phenols. The PoxR
      sensory domain detects phenols and relays signals for the activation of
      transcription. Here we report the first structure of the phenol sensory domain
      bound to phenol and five derivatives. It exists as a tightly intertwined
      homodimer with a phenol-binding pocket buried inside, placing two C termini on
      the same side of the dimer. His102 and Trp130 interact with the hydroxyl group of
      the phenol in a cavity surrounded by rigid hydrophobic residues on one side and a
      flexible region on the other. Each monomer has a V4R fold with a unique zinc
      binding site. A shift at the C-terminal helix suggests that there is a possible
      conformational change upon ligand binding. The results provide a structural basis
      of chemical effector binding for transcriptional regulation with broad
      implications for protein engineering. 

PMID- 27050688
TI  - Long-Range Communication between Different Functional Sites in the Picornaviral
      3C Protein.
AB  - The 3C protein is a master regulator of the picornaviral infection cycle,
      responsible for both cleaving viral and host proteins, and interacting with
      genomic RNA replication elements. Here we use nuclear magnetic resonance
      spectroscopy and molecular dynamics simulations to show that 3C is
      conformationally dynamic across multiple timescales. Binding of peptide and RNA
      lead to structural dynamics changes at both the protease active site and the RNA
      binding site, consistent with these sites being dynamically coupled. Indeed,
      binding of RNA influences protease activity, and likewise, interactions at the
      active site affect RNA binding. We propose that RNA and peptide binding re-shapes
      the conformational energy landscape of 3C to regulate subsequent functions,
      including formation of complexes with other viral proteins. The observed
      channeling of the 3C energy landscape may be important for regulation of the
      viral infection cycle. 

PMID- 27050691
TI  - Current Trends in Skin of Color.

PMID- 27050692
TI  - Camouflaging Agents for Vitiligo Patients.
AB  - Vitiligo is an acquired condition resulting in patches of depigmented skin that
      is cosmetically disfiguring and can subsequently be psychologically disturbing.
      For patients seeking to mask their vitiligo, camouflage options have historically
      been limited and been designated as a cosmetic, rather than a medical, concern.
      As research has indicated that proper concealment of vitiligo lesions can vastly
      improve quality of life, we believe it is essential that dermatologists become
      aware of all the options available to their patients and that discussions of
      camouflage options be broached from the first visit. Methods for concealment
      include cosmetic tattoos, dihydroxyacetone, general cosmetics, and various
      topical camouflage agents, including the newest product, MicroskinTM. We
      conducted a literature review of all of the available options for vitiligo
      concealment and evaluated their advantages and disadvantages. Ultimately,
      temporary methods of concealment are recommended; but the particular agent used
      can come from discussion with the patient based on the location of the lesions,
      degree of concealment desired, cost, and availability.

PMID- 27050693
TI  - Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory
      Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic
      Dermatitis.
AB  - Crisaborole topical ointment, 2% (formerly known as AN2728) is a benzoxaborole,
      nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor
      investigational compound that recently completed phase 3 studies for the
      treatment of mild to moderate atopic dermatitis (AD). The unique configuration of
      boron within the crisaborole molecule enables selective targeting and inhibition
      of PDE4, an enzyme that converts the intracellular second messenger 3'5'-cyclic
      adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate
      (AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole
      controls inflammation. The use of boron chemistry enabled synthesis of a low
      molecular-weight compound (251 daltons), thereby facilitating effective
      penetration of crisaborole through human skin. In vitro experiments showed that
      crisaborole inhibits cytokine production from peripheral blood mononuclear cells
      in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids.
      Crisaborole also displayed topical anti-inflammatory activity in a skin
      inflammation model. Once crisaborole reaches systemic circulation after topical
      application, it is metabolized to inactive metabolites. This limits systemic
      exposure to crisaborole and systemic PDE4 inhibition. In phase 1 and 2 clinical
      studies, crisaborole ointment, 2% was generally well tolerated and improved AD
      disease severity scores, pruritus, and all other AD signs and symptoms. Two
      large, randomized, controlled, phase 3, pivotal clinical trials assessing the
      efficacy and safety of crisaborole topical ointment, 2% in children, adolescents,
      and adults with mild to moderate AD were recently completed with positive
      results.

PMID- 27050694
TI  - Efficacy and Safety of Minoxidil 2% Solution in Combination With a Botanical Hair
      Solution in Women With Female Pattern Hair Loss/Androgenic Alopecia.
AB  - Female pattern hair loss (FPHL), also known as female androgenic alopecia,
      affects over 21 million women in the United States with devastating effects on
      self-esteem and psychosocial functioning. Topical minoxidil 2% and 5%
      formulations are the only US Food and Drug Administration-approved treatments for
      FPHL. The length of time it typically takes to observe the benefits is a
      challenge for many patients, and may affect adherence to treatment. Herbal
      extracts, which are also believed to promote healthier-looking hair, have a long
      history of use in hair care formulations. The safety and efficacy of a twice
      daily regimen of 2% minoxidil solution used in combination with the botanical
      hair solution for 12 weeks in 54 subjects was evaluated in a multicenter, single
      arm, open-label study. Assessments included investigator and subject ratings of
      improvement and subject satisfaction. Investigator ratings indicated significant
      improvement in hair growth and overall treatment benefits in as early as 6 weeks
      (P<.001). Subject self-ratings indicated significant satisfaction with hair
      volume and quality improvement at week 6 (P<.001). Subjects also indicated an
      increase in self-confidence and attractiveness at week 12 (P<.001). The
      investigator and subject-assessed efficacy and subject satisfaction with this
      regimen provides clinicians with an effective treatment option for FPHL that also
      provides a high level of patient acceptance, which ultimately may help promote
      minoxidil treatment adherence.

PMID- 27050695
TI  - Efficacy and Safety of Minoxidil 5% Foam in Combination With a Botanical Hair
      Solution in Men With Androgenic Alopecia.
AB  - Androgenic alopecia (AGA) is the most common type of hair loss in men,
      characterized by hair miniaturization, hairline recession, and vertex balding. It
      affects approximately 50% of men, negatively affecting self-esteem and
      sociability. Topical minoxidil formulations are approved up to a 5% concentration
      for men, but patient adherence to treatment is challenged by gradual results that
      may be perceived as a lack of initial benefit. Herbal extracts, which are also
      believed to promote healthier-looking hair, have a long history of use in hair
      care formulations. The safety and efficacy of a twice-daily regimen of 5%
      minoxidil foam used in combination with a novel botanical hair solution was
      evaluated in a 12-week, multicenter, single-arm, open label study in 56 subjects
      with mild to moderate AGA. Assessments included investigator ratings of
      improvement and subject self-ratings of satisfaction. Investigator ratings
      indicated significant improvement in scalp hair coverage and perception of
      overall treatment benefit in as early as 4 weeks (P<.001). Subject self-ratings
      were significant for improved hair growth and hair appearance in as few as 4
      weeks (P<.05). The regimen was well tolerated, and subjects indicated a high
      degree of satisfaction. Investigator and subject-assessed efficacy and subject
      satisfaction with this novel regimen provide clinicians with an effective
      treatment option for AGA that also provides a high level of patient satisfaction,
      which may help promote patient adherence to long-term treatment.

PMID- 27050696
TI  - Side Effects Related to 5 alpha-Reductase Inhibitor Treatment of Hair Loss in
      Women: A Review.
AB  - 5 alpha-reductase inhibitors such as finasteride and dutasteride have been
      studied for the treatment of hair loss in men, with finasteride being the only
      Food and Drug Administration-approved treatment. Increasingly, in recent years,
      off-label use of these drugs has been employed in the treatment of female pattern
      hair loss (FPHL) and frontal fibrosing alopecia (FFA) in women. Side effects with
      5 alpha-reductase inhibitors can include changes in sexual function, and recent
      publications have characterized an increasing prevalence of these in men. A
      review of 20 peer-reviewed articles found that very few side effects, or adverse
      events, related to sexual function have been reported in studies in which
      dutasteride or finasteride has been used to treat hair loss in women. Future
      publications should investigate not only the efficacy of these drugs in treating
      FPHL and FFA, but the side effect profile in patients as well.

PMID- 27050697
TI  - Objective Melanin Measurements: Review of Novel Dosimetry Guidance Device for
      Intense Pulsed Light in Aesthetic Treatments.
AB  - A melanin meter has been created to assess real time skin pigmentation to
      optimize settings for visible light aesthetic applications. METHODS: A handheld
      meter was applied to non sun-damaged skin on the back of volunteers to measure
      skin pigmentation prior to treatment with IPL light sources over a range of pulse
      widths and ascending fluences. Curves for maximum epidermal tolerances as a
      function of pigmentation were determined. These curves were then tabulated for
      each pulse width in device software to provide guidance in the selection of
      fluences. Based on these findings, the device was applied in over 300 patients at
      a comprehensive laser and cosmetic dermatology center. RESULTS: A pigment meter
      evaluation led to treatment parameter guidance in intense pulsed light
      applications. These suggested ranges for settings based on the melanin index
      score proved useful, accurate, and safe in applications over a broad range of
      skin colors and across various anatomic units of the skin. CONCLUSION: A pigment
      meter can be used to identify appropriate settings with IPL treatments in order
      to enhance safety and efficacy when treating epidermal pigmented lesions,
      vessels, general photodamage and excessive hair (where the principles of
      selective photothermolysis are applied).

PMID- 27050698
TI  - Pilot Comparative Study of the Topical Action of a Novel, Crosslinked Resilient
      Hyaluronic Acid on Skin Hydration and Barrier Function in a Dynamic, Three
      Dimensional Human Explant Model.
AB  - BACKGROUND: Hyaluronic acid (HA) is a popular ingredient in topical formulations
      for cosmetic improvement of the skin. Most formulations contain linear, non
      crosslinked HA oligomers, low molecular weight (LMW) HA, and/or high molecular
      weight (HMW) HA. Crosslinking of HA enhances its clinical longevity and
      mechanical characteristics. The objective of this study was to characterize the
      topical effects of a new, crosslinked resilient HA (RHA) that is also available
      as a cohesive, tissue-integrating injectable filler, compared with non
      crosslinked HMW HA and LMW HA. Living human skin explants that preserve the 3
      dimensional structure of in vivo skin were used to maximize clinical relevance.
      METHODS: Standardized doses of each HA product were applied daily for 9 days to
      human skin explant surfaces. Untreated explants served as controls. Water content
      of the stratum corneum and entire epidermis was analyzed by Raman spectroscopy.
      Transepidermal water loss (TEWL) was measured to assess skin barrier function.
      Explant morphology and microrelief were evaluated by optical and scanning
      electron microscopy. RESULTS: Crosslinked RHA achieved a significant increase in
      epidermal water content (7.6%) over the control. Spectral cartography confirmed a
      higher epidermal water content with RHA than with HMW HA or LMW HA. TEWL was
      reduced by 27.8% with RHA, and by 15.6% with HMW HA, but increased by 55.5% with
      LMW HA. Cutaneous microrelief improved with RHA. Corneocyte cohesion improved
      with RHA and HMW HA. CONCLUSIONS: This comparative, multimodal study demonstrated
      greater benefits of topical crosslinked RHA over linear HMW HA or LMW HA in
      reducing TEWL, retaining and redistributing water within the epidermis,
      maintaining skin integrity, and improving skin barrier structure and function.
      RHA was a more efficacious humectant than LMW HA, and a more efficacious
      occlusive moisturizer than HMW HA. These integrative epidermal repair activities
      are of significant value for addressing primary deficits of aging skin, improving
      tolerance to retinoids and other topical agents, and optimizing procedural
      outcomes. A combination of topical and injectable HA provides an elegant model of
      synergistic, multi-level skin restoration.

PMID- 27050699
TI  - Combination Superficial Peels With Salicylic Acid and Post-Peel Retinoids.
AB  - BACKGROUND: Salicylic acid (SA) and retinoids, tretinoin (all-trans retinoic acid
      [ATRA]), and retinol (all-trans retinol) are widely used as topical agents for
      the improvement of photodamage and acne vulgaris. They can be used in daily take
      home products or as part of an in-office procedure, combining the benefits of a
      keratolytic (SA) and a retinoid. OBJECTIVE: The objective of this research was to
      compare the efficacy for ameliorating photodamage of topical tretinoin (0.25%)
      and retinol (0.25%) to baseline and with each other when applied after a 30%
      salicylic acid peel on human facial skin. METHODS: Twenty female subjects
      received a full face 30% SA peel followed by the overnight application of
      tretinoin to a 1 randomized half-face and retinol to the opposite side (split
      face study). The identical procedure was repeated at week 2. Double-blinded
      subject and investigator assessments of the results were captured at weeks 2 and
      4. RESULTS: By investigator evaluation, both peeling regimens were effective in
      improving photodamage parameters compared to baseline. (ATRA P-values at week 4
      were: P=.00008 texture, P=.00013 roughness, P=.00221 pores, P=.00098 dryness,
      P=.02770 erythema, and P=.00008 overall appearance. Retinol P-values at week 4
      were: P=.00019 texture, P=.00053 roughness, P=.00221 pores, P=.00147 dryness,
      P=.02770 erythema, and P=.0043 overall appearance.) By subject self-assessment
      compared with baseline, both tretinoin and retinol were effective in improving
      overall appearance (ATRA P=.0229 and retinol P=.0190). By investigator evaluation
      comparing tretinoin with retinol, tretinoin was slightly better than retinol at
      week 4 in improving texture P=.00506, roughness P=.01171, and overall appearance
      P=.00506. By subject self-assessment comparing tretinoin with retinol, there was
      no difference in overall appearance (ATRA P=.2367 and retinol P=.3613).
      CONCLUSION: Either topical tretinoin (0.25%) or retinol (0.25%) can be used
      safely and effectively when applied in office immediately after SA peeling to
      ameliorate signs of photoaging.

PMID- 27050700
TI  - An Approach to Cosmeceuticals.
AB  - The cosmeceutical industry is a multi-billion dollar, consumer-driven market.
      Products promise highly desirable anti-aging benefits, but are not subject to
      regulation. We present an introduction to cosmeceuticals for the general and
      cosmetic dermatologist, including definitions and explanations of key terms, an
      approach to the evidence base, a dissection of chamomile and green tea, two
      paradigmatic cosmeceutical products, and a window into the underlying psychology
      of this vast marketplace.

PMID- 27050701
TI  - A Novel Matrikine-Like Micro-Protein Complex (MPC) Technology for Topical Skin
      Rejuvenation.
AB  - This randomized, controlled, investigator-blinded study performed by an
      independent research organization evaluated the appearance of periorbital and
      perioral wrinkles following twice-daily application of a specific blend of
      matrikines and matrikine-like synthetic peptides for skin rejuvenation over a 6
      month period. Fine lines and wrinkles of 133 women, aged 38 years to 65 years,
      were assessed by an independent expert evaluator using a 5-point visual analogue
      score. Subjects were divided into 3 groups and randomized to receive either the
      matrikine-based technology (MPC) or 1 of the 2 materials containing traditional
      growth factors. Test materials were well tolerated, and all 3 significantly
      reduced the appearance of periorbital and perioral wrinkles after 3 and 6 months.
      In the group receiving the matrikine-based technology, periorbital wrinkles
      improved (>= 1 unit) in 28% of subjects after 1 month, in 65% after 3 months, and
      in 81% after 6 months. Perioral wrinkles improved (>= 1 unit) in 39% of subjects
      after 1 month, in 41% after 3 months, and in 59% after 6 months. Improvements in
      skin firmness, tactile roughness, and pore appearance were also observed with
      each test material. Use of MPC was associated with significantly improved skin
      elasticity after 2 months (20%) and at 6 months (16%), whereas the comparator
      materials had no significant effects on elasticity. This study demonstrates that
      topical use of a specific blend of matrikines and matrikine-like peptides is
      suitable for skin rejuvenation. It also provides evidence that topical use of
      this novel technology provides comparable results to other technologies that use
      traditional growth factors for skin rejuvenation, with an additional potential
      benefit of improved skin elasticity.

PMID- 27050702
TI  - Investigator-Blinded, Single-Center Study to Evaluate the Efficacy and
      Tolerability of a 4% Hydroquinone Skin Care System Plus 0.02% Tretinoin Cream in
      Mild-to-Moderate Melasma and Photodamage.
AB  - OBJECTIVE: To evaluate the treatment of mild-to-moderate epidermal melasma and
      photodamage using a 4% hydroquinone skin care system plus tretinoin 0.02% cream.
      METHODS: Single-center, investigator-blinded study in 39 adult females with mild
      to-moderate epidermal melasma, mild-to-marked pigmentation intensity, and
      Fitzpatrick skin type III to VI treated for 24 weeks. Improvements in melasma
      severity, pigmentation intensity, photodamage, and patient satisfaction were
      assessed at weeks 4, 8, 12, 18, and 24. Cutaneous tolerability was assessed by
      investigator (erythema, dryness, peeling) and patients (burning and stinging).
      Adverse events (AEs) were monitored throughout. RESULTS: Melasma severity,
      pigmentation intensity, and melasma area and severity index (MASI) scores
      relative to baseline were all significantly reduced from week 4 onward (P<.001).
      In addition, signs of facial photodamage were significantly improved. At week 24,
      87.9% of patients were "satisfied" or "very satisfied" with the overall treatment
      effectiveness and Quality of Life (QoL) was much improved. No patient
      discontinued due to lack of efficacy or treatment-related AEs. One patient (2.8%)
      reported severe cutaneous intolerability (erythema at week 4). CONCLUSION:
      Treating mild-to-moderate melasma using a 4% hydroquinone skin care system plus
      0.02% tretinoin cream can significantly reduce the severity and intensity of
      melasma and associated pigmentation, and improve signs of photodamage within four
      weeks. Treatment was generally well tolerated and associated with high levels of
      patient satisfaction.

PMID- 27050703
TI  - An Open Label Clinical Trial to Evaluate the Efficacy and Tolerance of a Retinol
      and Vitamin C Facial Regimen in Women With Mild-to-Moderate Hyperpigmentation and
      Photodamaged Facial Skin.
AB  - A 12-week open-label, single-center clinical usage trial was conducted to
      determine the effectiveness of a dual product regimen consisting of a 0.5%
      retinol treatment and an anti-aging moisturizer with 30% vitamin C in women with
      mild to moderate hyperpigmented and photodamaged facial skin. Clinical grading of
      several efficacy parameters, tolerability evaluations, subject self-assessment
      questionnaires, and digital photography were completed at baseline and at weeks
      4, 8, and 12. A total of 44 women completed the study. Effective ingredients
      incorporated into the 0.5% retinol treatment included encapsulated retinol for a
      retinol concentration of 0.5%, bakuchiol, and Ophiopogon japonicus root extract.
      The anti-aging moisturizer with 30% vitamin C contained 30% vitamin C in the form
      of tetrahexyldecyl ascorbate (THD ascorbate), alpha-tocopheryl acetate (vitamin
      E) and ubiquinone (coenzyme Q10). The facial regimen produced a statistically
      significant decrease (improvement) in clinical grading scores for all parameters
      assessed at weeks 8 and 12 when compared with baseline scores. In addition, the
      majority of these parameters were improved at week 4. The test regimen was well
      perceived by the subjects for various inquiries regarding facial skin condition,
      product efficacy, and product attributes. Several tolerability parameters were
      assessed with no statistically significant increase except for dryness. A
      statistically significant increase in clinical grading scores for dryness on the
      face occurred at weeks 4 and 8 when compared to baseline scores. The increase in
      dryness is expected when introducing a retinol product to a facial regimen and
      the dryness did not persist to the week 12 time point.

PMID- 27050704
TI  - Quantifying Depth of Injection of Hyaluronic Acid in the Dermis: Data from
      Clinical, Laboratory, and Ultrasound Settings.
AB  - Although manufacturers' instructions for use of dermal fillers ordinarily direct
      injection in the superficial, mid or deep dermis, or, in some cases, the
      hypodermis (subcutis), the precise depth of injection may not always be for
      injectors. In this article, investigators report findings gathered from
      histopathology, ultrasound, "live" one on one training injections, as well as
      application of a mathematical formula for depth calculation of the various layers
      within the dermis. Areas of particular interest are the superficial reticular
      dermis and the mid dermis. Following the depth measurements detailed by Della
      Volpe et al in 2012, investigators compare and contrast their own depth findings
      of the various layers, arriving at the conclusion that the depth of the dermis is
      not as deep as had been previously assumed. The investigators also develop an
      argument for the appropriate angles of injection for placement of dermal filler
      into the various layers, demonstrating that the heretofore widely used angles of
      30 and 45 are far more acute than required.

PMID- 27050705
TI  - Contactless Abdominal Fat Reduction With Selective RFTM Evaluated by Magnetic
      Resonance Imaging (MRI): Case Study.
AB  - BACKGROUND: Noninvasive body shaping methods seem to be an ascending part of the
      aesthetics market. As a result, the pressure to develop reliable methods for the
      collection and presentation of their results has also increased. The most used
      techniques currently include ultrasound measurements of fat thickness in the
      treated area, caliper measurements, bioimpedance-based scale measurements or
      circumferential tape measurements. Although these are the most used techniques,
      almost all of them have some limitations in reproducibility and/or accuracy. This
      study shows Magnetic Resonance Imaging (MRI) as the new method for the
      presentation of results in the body shaping industry. MATERIALS AND METHODS: Six
      subjects were treated by a contactless selective radiofrequency device (BTL
      Vanquish ME, BTL Industries Inc., Boston, MA). The MRI fat thickness was measured
      at the baseline and at 4-weeks following the treatment. In addition to MRI images
      and measurements, digital photographs and anthropometric evaluations such as
      weight, abdominal circumference, and caliper fat thickness measurements were
      recorded. Abdominal fat thickness measurements from the MRI were performed from
      the same slices determined by the same tissue artefacts. RESULTS: The MRI fat
      thickness difference between the baseline measurement and follow up visit showed
      an average reduction of 5.36 mm as calculated from the data of 5 subjects. One
      subject dropped out of study due to non-study related issues. The results were
      statistically significant based on the Student's T-test evaluation. CONCLUSIONS:
      Magnetic resonance imaging abdominal fat thickness measurements seems to be the
      best method for the evaluation of fat thickness reduction after non-invasive body
      shaping treatments. In this study, this method shows average fat thickness
      reduction of 5.36 mm while the weight of the subjects didn't change
      significantly. A large spot size measuring 1317 cm(2) (204 square inches) covers
      the abdomen flank to flank. The average thickness of 5.36 mm of the fat layer
      reduced under the applicator translates into significant cumulative
      circumferential reduction. The reduction was not related with dieting.

PMID- 27050706
TI  - Assessment of a Novel Anti-Aging Hand Cream.
AB  - There are few creams that have been developed for the purpose of treating the
      aging hand, yet UV damage and secondary signs of aging on the hands make them one
      of the most obvious indicators of age outside the face. This study documents
      results of a 120 day trial using a novel cream preparation containing ingredients
      including Retinol, Alpha-Arbutin, Kojic Dipalmitate, Azaeleic Acid,
      Hexylresorcinol, Licorice Root, and other ingredients. Results were tabulated
      comparing physician and patient assessment scores using a comprehensive scoring
      assay, which showed significant improvements across eight parameters tested. This
      was statistically significant for physician ratings of texture, wrinkles and
      pigment at 120 days versus baseline (P < 0.001). Further research is needed, but
      the results appear to indicate the benefits of a targeted hand cream in improving
      the appearance of the aging hand.

PMID- 27050707
TI  - Extracellular Matrix Modulation: Optimizing Skin Care and Rejuvenation
      Procedures.
AB  - Normal aging and photoaging of the skin are chronic processes that progress
      gradually. The extracellular matrix (ECM), constituting over 70% of the skin, is
      the central hub for repair and regeneration of the skin. As such, the ECM is the
      area where changes related to photodamage are most evident. Degradation of the
      ECM with fragmentation of proteins significantly affects cross talk and signaling
      between cells, the matrix, and its constituents. The accumulation of collagen
      fragments, amorphous elastin agglutinations, and abnormal cross-linkages between
      the collagen fragments impedes the ECM from its normal repair and regenerative
      capacity, which manifests as wrinkled, non-elastic skin. Similar to how the
      chronic wound healing process requires wound bed preparation before therapeutic
      intervention, treatment of chronic aging of the skin would likely benefit from a
      "skin bed preparation" to optimize the outcome of rejuvenation procedures and
      skin maintenance programs. This involves introducing agents that can combat
      stress-induced oxidation, proteasome dysfunction, and non-enzymatic cross
      linkages involved in glycation end products, to collectively modulate this
      damaged ECM, and upregulate neocollagenesis and elastin production. Agents of
      particular interest are matrikines, peptides originating from the fragmentation
      of matrix proteins that exhibit a wide range of biological activities. Peptides
      of this type (tripeptide and hexapeptide) are incorporated in ALASTINTM Skin
      Nectar with TriHexTM technology (ALASTIN Skincare, Inc., Carlsbad, CA), which is
      designed to target ECM modulation with a goal of optimizing results following
      invasive and non-invasive dermal rejuvenating procedures.

PMID- 27050708
TI  - The role of chronic pain and current substance use in predicting negative social
      support among disadvantaged persons living with HIV/AIDS.
AB  - Chronic pain and substance use can strain the supportive relationships of persons
      with serious chronic illness, which may increase the likelihood of receiving
      negative, rather than positive, social support from informal caregivers and
      social network members. To our knowledge, this is the first study to
      longitudinally examine the effects of chronic pain and substance use on negative
      social support. The sample (N = 383) comprised disadvantaged, primarily African
      American, persons living with HIV/AIDS with a history of injection drug use,
      32.4% of whom reported frequent or constant pain in the prior 6 months. Using
      factor analysis and structural equation modeling, current substance use and
      greater levels of chronic pain positively predicted negative social support 12
      months later, after controlling for baseline negative support, viral load, age
      and sex. We also found a significant interaction effect such that among those not
      using substances, there was a significant positive association between pain and
      negative support, but no such association among those currently using substances.
      The findings emphasize the importance of treatment of chronic pain and substance
      use in the supportive functioning of social networks of a disadvantaged
      population with serious chronic conditions and persistent health disparities.

PMID- 27050709
TI  - Effects of fixed vs. self-suggested rest between sets in upper and lower body
      exercises performance.
AB  - In its last position stand about strength training, the American College of
      Sports Medicine recommends a rest interval (RI) between sets ranging between 1
      and 3 min, varying in accordance with the objective. However, there is no
      consensus regarding the optimal recovery between sets, and most studies have
      investigated fixed intervals. Therefore, the aim of this study was to analyse the
      effects of fixed versus self-suggested RI between sets in lower and upper body
      exercises performance. Twenty-seven healthy subjects (26 +/- 1.5; 75 +/- 15 kg;
      175 +/- 12 cm) were randomly assigned into two groups: G1: lower body exercises
      and G2: upper body exercises. Squat and leg press 1 repetition maximum (1RM) were
      tested for the G1 and bench press and biceps curl 1RM for G2. After the 1RM
      tests, both groups performed three sets to concentric failure with 75% of 1RM in
      combination with different RIs (2 min or self-suggested) on separate days and the
      exercises performance was evaluated by the number of repetitions. The results
      demonstrated no significant differences in the number of repetitions between 2
      min and self-suggested RIs that presented similar reductions with the sets
      progression. It was also shown that the self-suggested RI spent less time
      recovering than the 2 min RI group on average. This suggests that for individuals
      with previous experience, the self-suggested RI can be an effective option when
      using workloads commonly prescribed aiming hypertrophy. Also, the self-suggested
      RI can reduce the total training session duration, which can be a more time
      effective strategy. 

PMID- 27050710
TI  - First-Principles Atomic Force Microscopy Image Simulations with Density Embedding
      Theory.
AB  - We present an efficient first-principles method for simulating noncontact atomic
      force microscopy (nc-AFM) images using a "frozen density" embedding theory.
      Frozen density embedding theory enables one to efficiently compute the tip-sample
      interaction by considering a sample as a frozen external field. This method
      reduces the extensive computational load of first-principles AFM simulations by
      avoiding consideration of the entire tip-sample system and focusing on the tip
      alone. We demonstrate that our simulation with frozen density embedding theory
      accurately reproduces full density functional theory simulations of freestanding
      hydrocarbon molecules while the computational time is significantly reduced. Our
      method also captures the electronic effect of a Cu(111) substrate on the AFM
      image of pentacene and reproduces the experimental AFM image of Cu2N on a Cu(100)
      surface. This approach is applicable for theoretical imaging applications on
      large molecules, two-dimensional materials, and materials surfaces.

PMID- 27050711
TI  - Facile template-free synthesis of vertically aligned polypyrrole nanosheets on
      nickel foams for flexible all-solid-state asymmetric supercapacitors.
AB  - This paper reports a novel and remarkably facile approach towards vertically
      aligned nanosheets on three-dimensional (3D) Ni foams. Conducting polypyrrole
      (PPy) sheets were grown on Ni foam through the volatilization of the
      environmentally friendly solvent from an ethanol-water solution of pyrrole (Py),
      followed by the polymerization of the coated Py in ammonium persulfate (APS)
      solution. The PPy-decorated Ni foams and commercial activated carbon (AC)
      modified Ni foams were employed as the two electrodes for the assembly of
      flexible all-solid-state asymmetric supercapacitors. The sheet-like structure of
      PPy and the macroporous feature of the Ni foam, which render large electrode
      electrolyte interfaces, resulted in good capacitive performance of the
      supercapacitors. Moreover, a high energy density of ca. 14 Wh kg(-1) and a high
      power density of 6.2 kW kg(-1) were achieved for the all-solid-state asymmetric
      supercapacitors due to the wide cell voltage window. 

PMID- 27050712
TI  - Prophylactic hyperthermic intraperitoneal chemotherapy in patients with
      epithelial appendiceal neoplasms.
AB  - Background Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) is a
      promising approach for preventing peritoneal carcinomatosis in high-risk
      patients. We report our initial experience with prophylactic HIPEC in a series of
      patients with appendiceal neoplasms. Methods We retrospectively reviewed our
      prospectively maintained database to identify patients who underwent HIPEC in the
      absence of peritoneal disease. Patients with previously documented peritoneal
      surface disease were excluded. Data regarding clinical, operative and
      pathological features were analysed. Results Out of 322 HIPEC procedures
      performed between March 2007and August 2015, we identified 16 patients who
      underwent surgery with prophylactic intent. Primary diagnoses included high-grade
      and low-grade appendiceal neoplasms. Most patients presented originally with
      appendiceal perforation; all patients underwent initial surgery during which the
      appendix or right colon were resected. Following a median time interval of 2.2
      months, a second surgery performed at our institution consisted of completion of
      omentectomy, partial colectomy and oophorectomy, with administration of
      prophylactic HIPEC (using mitomycin C). A totally laparoscopic approach was
      attempted and achieved in 11 patients in whom the median duration of surgery,
      estimated intraoperative blood loss and length of hospitalisation were 251 min,
      100 cm(3) and 4 days, respectively. There were no cases of major perioperative
      morbidity or mortality. Conclusions Prophylactic HIPEC for appendiceal neoplasms
      is feasible, safe and may be performed laparoscopically. Larger studies with long
      term follow-up are needed to determine whether a survival benefit is associated
      with this treatment.

PMID- 27050713
TI  - Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of
      Toll-like Receptor-4 (TLR4) Agonists.
AB  - Herein, we report studies leading to the discovery of the neoseptins and a
      comprehensive examination of the structure-activity relationships (SARs) of this
      new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The
      compounds in this class, which emerged from screening an alpha-helix mimetic
      library, stimulate the immune response, act by a well-defined mechanism (mouse
      TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite
      SARs, are nontoxic, and elicit improved and qualitatively different responses
      compared to lipopolysaccharide, even though they share the same receptor.

PMID- 27050714
TI  - The impact of emotion awareness and regulation on social functioning in
      individuals at clinical high risk for psychosis.
AB  - BACKGROUND: Social functioning (SF) difficulties are ubiquitous among individuals
      at clinical high risk for psychosis (CHR), but it is not yet clear why. One
      possibility is suggested by the observation that effective SF requires adaptive
      emotion awareness and regulation. Previous reports have documented deficits in
      emotion awareness and regulation in individuals with schizophrenia, and have
      shown that such deficits predicted SF. However, it is unknown whether these
      deficits are present prior to the onset of psychosis or whether they are linked
      to SF in CHR individuals. METHOD: We conducted a cross-sectional comparison of
      emotion awareness and regulation in 54 individuals at CHR, 87 with schizophrenia
      and 50 healthy controls (HC). Then, within the CHR group, we examined links
      between emotion awareness, emotion regulation and SF as indexed by the Global
      Functioning Scale: Social (Cornblatt et al. 2007). RESULTS: Group comparisons
      indicated significant differences between HC and the two clinical groups in their
      ability to identify and describe feelings, as well as the use of suppression and
      reappraisal emotion-regulation strategies. Specifically, the CHR and
      schizophrenia groups displayed comparable deficits in all domains of emotion
      awareness and emotion regulation. A hierarchical multiple regression analysis
      indicated that difficulties describing feelings accounted for 23.2% of the SF
      variance. CONCLUSIONS: The results indicate that CHR individuals display
      substantial emotion awareness and emotion-regulation deficits, at severity
      comparable with those observed in individuals with schizophrenia. Such deficits,
      in particular difficulties describing feelings, predate the onset of psychosis
      and contribute significantly to poor SF in this population.

PMID- 27050715
TI  - Sarcomatoid Carcinoma of the Urinary Bladder.
AB  - Sarcomatoid carcinoma of the urinary bladder (SCUB) is a rare and aggressive
      subtype of bladder cancer that has a poor prognosis. Limited information is
      available regarding its clinical features and appropriate treatments. A
      systematic literature search for published reports on SCUB was performed in the
      MEDLINE database using the key words "bladder cancer," "sarcomatoid carcinoma,"
      and "carcinosarcoma.". The search resulted in the identification of 276 reports
      published from January 1960 to January 2014, of which 40 were ultimately included
      in the present review. No prospective study or clinical trial of SCUB was
      reported in English language studies. Of these studies, 2 cancer registry studies
      and 13 large case series, which had included >= 8 cases were identified. Seven
      single-institution studies contained adequate clinical follow-up information, and
      the rest had mainly focused on the pathologic features of the disease. Both the
      registry and the single-institution studies showed that patients with SCUB
      presented with a high histologic grade, advanced-stage disease, and a poor
      prognosis. Comparing the single-institution studies to the Surveillance,
      Epidemiology, and End Results cohorts, significant differences were found in the
      age at diagnosis, male-to-female ratio, tumor stage, treatment pattern
      (cystectomy, radiation, and chemotherapy), and outcomes, likely reflecting
      differences in referral and practice patterns. The tumor stage was identified as
      a significant predictor for cancer-specific survival. The results of the present
      study suggest that SCUB is not as rare as previously thought. Patients with SCUB
      should be referred to specialists or centers with extensive experience with this
      rare and serious disease.

PMID- 27050716
TI  - Prognostic Factors of Adjuvant Taxane, Cisplatin, and 5-Fluorouracil Chemotherapy
      for Patients With Penile Squamous Cell Carcinoma After Regional Lymphadenectomy.
AB  - BACKGROUND: Little is known about the outcomes and prognostic factors of adjuvant
      chemotherapy for locally advanced penile squamous cell carcinoma after regional
      lymphadenectomy (LAD). PATIENTS AND METHODS: We retrospectively reviewed the data
      from 21 patients who had received taxane, cisplatin, and 5-fluorouracil (TPF,
      every 3 weeks) in the adjuvant setting at our center. Univariable and
      multivariable Cox regression analyses were undertaken for disease-free (DFS) and
      overall survival (OS) of TPF. RESULTS: The patients had received TPF from July
      2004 to July 2012 after inguinal (n = 6) or inguinal plus pelvic LAD (n = 15),
      and the median follow-up was 52 months. Thirteen (61.9%) had pelvic and 5 (23.8%)
      bilateral inguinal nodal metastases. The median time from LAD to the start of TPF
      was 5.4 weeks (interquartile range [IQR], 4.1-7.3 weeks). Metastatic tumor tissue
      from 11 of 19 evaluable patients (57.9%) showed positive immunohistochemistry
      staining for p53. Univariably, only the expression of p53 showed a trend toward
      poorer DFS (hazard ratio [HR], 4.14; 95% confidence interval [CI], 0.87-19.68; P
      = .074) and OS (HR, 4.54; 95% CI, 0.95-21.56; P = .056). The same results were
      obtained multivariably for DFS (HR, 3.76; 95% CI, 0.78-17.96; P = .096) and OS
      (HR, 4.29; 95% CI, 0.89-20.57; P = .067). The median DFS was 8.9 months (IQR, 5.9
      22.7 months) for p53-expressing patients versus not estimable for non-p53
      expressing patients (P = .051) and the median OS was 17.2 months (IQR, 12.8-22.7
      months) and not estimable, respectively (P = .037). CONCLUSION: In patients who
      had received adjuvant TPF for node-positive penile squamous cell carcinoma, p53
      IHC expression seemed to be associated with a poorer outcome, and further study
      is warranted in larger data sets to confirm these findings. This information
      might be useful to improve the prognostic allocation.

PMID- 27050717
TI  - Neuroanniversary 2017.

PMID- 27050719
TI  - Exquisite Modulation of the Active Site of Methanocaldococcus jannaschii
      Adenylosuccinate Synthetase in Forward Reaction Complexes.
AB  - In enzymes that conduct complex reactions involving several substrates and
      chemical transformations, the active site must reorganize at each step to
      complement the transition state of that chemical step. Adenylosuccinate
      synthetase (ADSS) utilizes a molecule each of guanosine 5'-monophosphate (GTP)
      and aspartate to convert inosine 5'-monophosphate (IMP) into succinyl adenosine
      5'-monophosphate (sAMP) through several kinetic intermediates. Here we followed
      catalysis by ADSS through high-resolution vibrational spectral fingerprints of
      each substrate and intermediate involved in the forward reaction. Vibrational
      spectra show differential ligand distortion at each step of catalysis, and band
      positions of substrates are influenced by binding of cosubstrates. We found that
      the bound IMP is distorted toward its N1-deprotonated form even in the absence of
      any other ligands. Several specific interactions between GTP and active-site
      amino acid residues result in large Raman shifts and contribute substantially to
      intrinsic binding energy. When both IMP and GTP are simultaneously bound to ADSS,
      IMP is converted into an intermediate 6-phosphoryl inosine 5'-monophosphate (6
      pIMP). The 6-pIMP.ADSS complex was found to be stable upon binding of the third
      ligand, hadacidin (HDA), an analogue of l-aspartate. We find that in the absence
      of HDA, 6-pIMP is quickly released from ADSS, is unstable in solution, and
      converts back into IMP. HDA allosterically stabilizes ADSS through local
      conformational rearrangements. We captured this complex and determined the
      spectra and structure of 6-pIMP in its enzyme-bound state. These results provide
      important insights into the exquisite tuning of active-site interactions with
      changing substrate at each kinetic step of catalysis.

PMID- 27050718
TI  - Collagenase Clostridium histolyticum: emerging practice patterns and treatment
      advances.
AB  - OBJECTIVE: This study aims to provide a comprehensive review of the role of
      Collagenase Clostridium histolyticum (CCH). METHODS: This review is based on a
      literature review and practical experience. RESULTS: This review provides
      practical management strategies for using collagenase by sharing clinical
      experiences over the past few years; logistical aspects of in-clinic treatment,
      lessons learned, and novel approaches to correct traditionally hard-to-treat
      contractures are discussed. In addition a brief, yet comprehensive overview is
      provided on the pathophysiology of the disease, the mechanism of collagenase
      action and results of clinical studies. CONCLUSION: CCH has an evolving role as
      one of the tools available for treating Dupuytren's disease.

PMID- 27050720
TI  - Sesquiterpenoids from the seeds of Sarcandra glabra and the potential anti
      inflammatory effects.
AB  - Five new sesquiterpenoids, including two linderanes (1-2) and three eudesmanes (3
      5) were isolated from the seeds of Sarcandra glabra. Their structures and
      relative configurations were established by spectroscopic data analysis. 1 was a
      rare linderane derivative having an 18-membered triester ring which is a common
      characteristic in linderane dimers. Compounds 1-5 were investigated for their
      inhibitory effects on NO production in LPS-induced macrophages and 1 showed
      moderate bioactivity. 

PMID- 27050721
TI  - Enhanced anti-tumor activity of trichosanthin after combination with a human
      derived cell-penetrating peptide, and a possible mechanism of activity.
AB  - Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP-I) and renowned
      Chinese traditional medicine, displays a broad spectrum of biological and
      pharmacological properties. Particularly, its anti-tumor activity has received a
      great deal of attention. However, the cellular mechanism for TCS uptake varies
      with different tumor cell lines, leading to discrepancies in its reported ability
      to penetrate cells. In this study, HBD, a human derived cell-penetrating peptide
      (CPP), was used to improve the delivery of TCS into several types of tumor cells,
      including HeLa cells. Recombinant TCS (rTCS) with or without the fused HBD
      peptide was expressed in Escherichia coli cells and successfully purified by Ni
      NTA affinity chromatography. The cellular uptake efficiency of FITC-labelled-rTCS
      HBD was observed in HeLa cells and compared with the uptake efficiency of non-HBD
      conjugated rTCS under the same conditions using laser confocal microscopy.
      Moreover, the IC50 value of rTCS-HBD in the tested tumor cells was much lower
      than that of rTCS, indicating that HBD could efficiently deliver the rTCS into
      tumor cells. When compared with rTCS, rTCS-HBD induced higher rates of apoptosis
      in HeLa cells as analyzed by flow cytometry. Furthermore, the apoptotic events
      observed in HeLa cells incubated with HBD-fused rTCS included activation of
      Caspase-9, decrease in the Bcl-2/Bax ratio, and cleavage of PARP. These results
      strongly suggest the participation of mitochondria in apoptosis. This report
      illustrates one possible method for achieving the efficient transport of TCS into
      cells using a CPP as a vector, and increases the likelihood that TCS can be used
      in the clinic. 

PMID- 27050722
TI  - Clinicopathological features and risk factors analysis of IgA nephropathy
      associated with acute kidney injury.
AB  - OBJECTIVE: The aim of this work is to investigate the distinctive
      clinicopathological characteristics of AKI in Chinese IgAN population and
      possible risk factors for AKI. METHODS: We performed a retrospective analysis of
      1512 patients with biopsy-proven primary IgAN in the period 2006 through 2011 in
      The First Affiliated Hospital of Sun Yat-sen University. AKI was defined as 2012
      KDIGO (Kidney Diseases: Improving Global Outcomes) criteria, and the patients
      were divided into AKI group (n = 145) and non-AKI group (n = 1367). RESULTS: The
      prevalence of AKI of the IgAN patients in our center was 9.59% (145/1512). Most
      AKI patients were older age, male, with higher percentage of smoke, hypertension,
      hyperlipidemia and preexisting impaired kidney function (Scr > 133 MUmol/L), and
      higher serum creatinine, proteinuria, uric acid, whilst less onset of macroscopic
      hematuria as well as lower serum albumin and hemoglobin (p < 0.05). The
      pathological features were much more severe in AKI group as well. Acute
      tubulointerstitial nephritis was found as the most predominant pathological
      change of intrinsic AKI in our IgAN population instead of macroscopic hematuria
      associated acute tubular injury/necrosis. In multivariate logistic regression
      analysis, we found that older age, male gender, malignant hypertension,
      proteinuria, cellular crescent, fibrocellular crescent, glomerular sclerosis >=
      50% were possible risk factors for AKI. CONCLUSIONS: AKI is commonly seen among
      IgAN population. The clinicopathological features are much more severe in IgAN
      patients with AKI. Useful clinicopathological predictors are recognized to
      improve the identification of IgAN patients who are at high risk for AKI.

PMID- 27050723
TI  - The management of asthma in the phenotype and biomarker era: The proposal of a
      new diagnostic-therapeutic model.
AB  - Treatment goals in asthma patients are the achievement of a good control of
      symptoms and the reduction of the risk of exacerbation. However, a "one-size-fits
      all" therapeutic strategy is no longer appropriate to effectively pursue these
      goals, due to the heterogeneity of asthma. To make the treatment scenario even
      more complex, asthma patients often present comorbidities that may alter response
      to therapy. In addition, adherence to asthma treatment is poor. Given this
      complex and heterogeneous picture, the management of asthma is highly
      challenging. A clear diagnostic-therapeutic model of patients' care and the
      definition of the specific responsibilities of different healthcare providers
      appear necessary to improve clinical outcomes and better allocate healthcare
      resources. We present here a proposal for this model.

PMID- 27050724
TI  - Vitamin D, disease activity and comorbidities in early spondyloarthritis.
AB  - OBJECTIVES: To assess the vitamin D status in patients presenting inflammatory
      back pain suggestive of axial spondyloarthritis and to assess the relationship
      between vitamin D status and disease activity/severity; comorbidities at baseline
      and during the first two years of follow-up. METHODS: DESIR is a prospective,
      multicentre, observational study. Vitamin D deficiency was defined as <50 nmol/L
      and severe deficiency less than 25 nmol/L. Clinical variables were collected at
      each six month interval visits during the two-year follow-up. RESULTS: A total of
      700 patients were analysed. The mean vitamin D was 54.2+/-28.7 nmol/L. Severe
      deficiency were observed in 11.7% versus 5% in the DESIR cohort versus the French
      population respectively. In the DESIR cohort, after adjusting for season and
      ethnicity, vitamin D deficiency remained significantly associated with presence
      of radiological sacroiliitis, higher ASDAS score and elevated BASDAI. Such
      association was also found between vitamin D deficiency and the mean value of
      disease activity/severity parameters during the two-year follow-up. Otherwise,
      vitamin D deficiency was significantly associated with the presence of baseline
      abdominal obesity (OR=1.65 [1.05-2.61], p=0.03), low HDL (OR=1.71 [1.14-2.55],
      p=0.01) and presence of metabolic syndrome (OR=2.20 [1.04-4.64], p=0.03) at
      baseline. CONCLUSIONS: We found a higher percentage of patients with severe
      vitamin D deficiency in early axial spondyloarthritis. Vitamin D deficiency was
      associated with higher disease activity and severity and presence of metabolic
      syndrome. Further longitudinal studies are required to evaluate the interest of
      vitamin D supplementation on the long-term outcome of the disease.

PMID- 27050725
TI  - Parent Diet Quality and Energy Intake Are Related to Child Diet Quality and
      Energy Intake.
AB  - BACKGROUND: Parents' diets are believed to influence their children's diets.
      Previous studies have not adequately and simultaneously assessed the relationship
      between parent and child total diet quality and energy intakes. OBJECTIVE: Our
      aim was to investigate whether parent and child diet quality and energy intakes
      are related. DESIGN: We conducted a cross-sectional analysis using baseline
      dietary intake data from the Neighborhood Impact on Kids study collected in 2007
      to 2009. PARTICIPANTS/SETTING: Participants were parents and 6- to 12-year-old
      children from households in King County (Seattle area), WA, and San Diego County,
      CA, targeted by Neighborhood Impact on Kids were recruited. Eligible parent-child
      dyads (n=698) with two or three 24-hour dietary recalls were included in this
      secondary analysis. MAIN OUTCOME MEASURES: Child diet quality (Healthy Eating
      Index-2010, Dietary Approaches to Stop Hypertension score, and energy density
      [for food only]) and energy intake were derived from the dietary recalls using
      Nutrition Data Systems for Research. STATISTICAL ANALYSES PERFORMED: Multiple
      linear regression models examined the relationship between parent diet quality
      and child diet quality, and the relationship between parent energy intake and
      child energy intake. In both analyses, we controlled for parent characteristics,
      child characteristics, household education, and neighborhood type. RESULTS:
      Parent diet quality measures were significantly related to corresponding child
      diet quality measures: Healthy Eating Index-2010 (standardized beta=.39;
      P<0.001); Dietary Approaches to Stop Hypertension score (beta=.33; P<0.001); and
      energy density (beta=.32; P<0.001). Parent daily mean energy intake (1,763+/-524
      kcal) was also significantly related (beta=.30; P<0.001) to child daily mean
      energy intake (1,751+/-431 kcal). CONCLUSIONS: Parent and child intakes were
      closely related across various metrics of diet quality and for energy intake.
      Mechanisms of influence are likely to be shared food environments, shared meals,
      and parent modeling.

PMID- 27050726
TI  - Reliability and Validity of Food Frequency Questions to Assess Beverage and Food
      Group Intakes among Low-Income 2- to 4-Year-Old Children.
AB  - BACKGROUND: Fruits, vegetables, sweetened foods, and beverages have been found to
      have positive and negative associations with obesity in early childhood, yet no
      rapid assessment tools are available to measure intake of these foods among
      preschoolers. OBJECTIVE: This study examines the test-retest reliability and
      validity of a 10-item Child Food and Beverage Intake Questionnaire designed to
      assess fruits, vegetables, and sweetened foods and beverages intake among 2- to 4
      year-old children. METHODS: The Child Food and Beverage Intake Questionnaire was
      developed for use in periodic phone surveys conducted with low-income families
      with preschool-aged children. Seventy primary caregivers of 2- to 4-year-old
      children completed two Child Food and Beverage Intake Questionnaires within a 2
      week period for test-retest reliability. Participants also completed three 24
      hour recalls to allow assessment of validity. Intraclass correlations were used
      to examine test-retest reliability. Spearman rank correlation coefficients, Bland
      Altman plots, and linear regression analyses were used to examine validity of the
      Child Food and Beverage Intake Questionnaire compared with three 24-hour recalls.
      RESULTS: Intraclass correlations between Child Food and Beverage Intake
      Questionnaire administrations ranged from 0.48 for sweetened drinks to 0.87 for
      regular sodas. Intraclass correlations for fruits, vegetables, and sweetened food
      were 0.56, 0.49, and 0.56, respectively. Spearman rank correlation coefficients
      ranged from 0.15 to 0.59 for beverages, with 0.46 for sugar-sweetened beverages.
      Spearman rank correlation coefficients for fruits, vegetables, and sweetened food
      were 0.30, 0.33, and 0.30, respectively. Although observation of the Bland-Altman
      plots and linear regression analyses showed a slight upward trend in mean
      differences, with increasing mean intake for five beverage groups, at least 90%
      of data plots fell within the limits of agreement for all food/beverage groups.
      CONCLUSIONS: The Child Food and Beverage Intake Questionnaire exhibited fair to
      substantial test-retest reliability and moderate to strong validity in ranking
      fruits, vegetables, sweetened food, and the majority of beverages consumed by
      children aged 2 to 4 years old. Although the Child Food and Beverage Intake
      Questionnaire might not be able to assess the absolute intake of foods and
      beverages, given the scarcity of an easily administered, valid, and reliable
      questionnaire to assess nutritional intake among 2- to 4-year-old low-income
      children, this tool is a useful means for measuring trends in dietary intake
      among low-income preschoolers.

PMID- 27050727
TI  - The Challenge of Connecting Dietary Changes to Improved Disease Outcomes: The
      Balance between Positive, Neutral, and Negative Publication Results.

PMID- 27050729
TI  - Proline Absorption and SGK1 Expression are Inhibited in Intestinal Tis7
      Transgenic Mice.
AB  - BACKGROUND/AIMS: Expression of the transcriptional co-regulator tis7 is markedly
      increased in the adaptive small intestine in a mouse model of short bowel
      syndrome. Transgenic mice with enterocytic overexpression of tis7 (tis7tg) have
      accelerated triglyceride absorption, with increased adiposity yet reduced
      skeletal muscle mass. To further explore this phenotype, we examined whether tis7
      also regulates amino acid and carbohydrate absorption. METHODS: Small intestinal
      glucose and amino acid uptake were quantified in wild type (WT) and tis7tg mice.
      Amino acid transporter expression was assessed by qRT-PCR and immunoblot. Apical
      cell surface transporter expression was quantified by cell surface biotinylation.
      RESULTS: Active glucose uptake rates were unchanged. Uptake of proline but not
      leucine was significantly reduced in tis7tg vs. WT jejunum. Expression of serum
      and glucocorticoid-induced kinase 1 (SGK1), a solute carrier activator, was
      inhibited in tis7tg jejunum. Apical membrane expression of the proline
      transporter SLC6A20 was reduced in tis7tg jejunum. CONCLUSIONS: Tis7
      overexpression in enterocytes inhibits proline uptake, associated with decreased
      expression of activated SGK1 and reduced cell surface expression of SLC6A20.
      Consistent with the observed tis7tg phenotype, tis7 overexpression increases
      triglyceride absorption but has adverse effects on the uptake of selected amino
      acids. Tis7 has pleiotropic effects on nutrient absorption.

PMID- 27050728
TI  - No Association between Dietary Patterns and Risk for Cognitive Decline in Older
      Women with 9-Year Follow-Up: Data from the Women's Health Initiative Memory
      Study.
AB  - BACKGROUND: Data on the association between dietary patterns and age-related
      cognitive decline are inconsistent. OBJECTIVE: To determine whether dietary
      patterns assessed by the alternate Mediterranean diet score (aMED), the Healthy
      Eating Index-2010 (HEI-2010), the Alternate Healthy Eating Index 2010 (AHEI
      2010), or the Dietary Approach to Stop Hypertension (DASH) diet score are
      associated with cognitive decline in older women, and to examine whether dietary
      patterns modify the risk for cognitive decline in women with hypertension.
      DESIGN: Prospective, longitudinal cohort study. Food frequency questionnaires
      were used to derive dietary patterns at baseline. Hypertension was defined as
      self-report of current drug therapy for hypertension or clinic measurement of
      systolic blood pressure >=140 mm Hg or diastolic blood pressure >=90 mm Hg.
      PARTICIPANTS AND SETTING: Postmenopausal women (N=6,425) aged 65 to 79 years who
      participated in the Women's Health Initiative Memory Study and were cognitively
      intact at baseline. MAIN OUTCOME MEASURES: Cognitive decline was defined as cases
      of mild cognitive impairment (MCI) or probable dementia (PD). Cases were
      identified through rigorous screening and expert adjudication. STATISTICAL
      ANALYSES PERFORMED: Cox proportional hazards models with multivariable adjustment
      were used to estimate the relative risk for developing MCI or PD. RESULTS: During
      a median follow-up of 9.11 years, we documented 499 cases of MCI and 390 of PD.
      In multivariable analyses we did not detect any statistically significant
      relationships across quintiles of aMED, HEI-2010, DASH, and AHEI-2010 scores and
      MCI or PD (P values for trend=0.30, 0.44, 0.23, and 0.45). In women with
      hypertension, we found no significant association between dietary patterns and
      cognitive decline (P values for trend=0.19, 0.08, 0.07, and 0.60). CONCLUSIONS:
      Dietary patterns characterized by the aMED, HEI-2010, AHEI-2010, or DASH dietary
      score were not associated with cognitive decline in older women. Adherence to a
      healthy dietary pattern did not modify the risk for cognitive decline in women
      with hypertension.

PMID- 27050730
TI  - Evaluating imbalances of adverse events during biosimilar development.
AB  - Biosimilars are designed to be highly similar to approved or licensed (reference)
      biologics and are evaluated based on the totality of evidence from extensive
      analytical, nonclinical and clinical studies. As part of the stepwise approach
      recommended by regulatory agencies, the first step in the clinical evaluation of
      biosimilarity is to conduct a pharmacokinetics similarity study in which the
      potential biosimilar is compared with the reference product. In the context of
      biosimilar development, a pharmacokinetics similarity study is not necessarily
      designed for a comparative assessment of safety. Development of PF-05280014, a
      potential biosimilar to trastuzumab, illustrates how a numerical imbalance in an
      adverse event in a small pharmacokinetics study can raise questions on safety
      that may require additional clinical trials.

PMID- 27050731
TI  - New insights into the role of T cells in pathogenesis of psoriasis and psoriatic
      arthritis.
AB  - Psoriasis is a chronic, relapsing, autoimmune disorder of the skin affecting 2-3%
      of general population. Approximately 30% of psoriasis patients are also affected
      with the psoriatic arthritis, a chronic inflammatory spondyloarthritis. The
      review aims to present the current knowledge on immunopathogenesis of both
      diseases to emphasize the involvement of various T helper cell subsets. An
      extensive literature search in electronic databases was performed on the topic of
      different Th cell subsets' involvement in the pathogenesis of psoriasis and
      psoriatic arthritis. Studies were assessed and selected to present the recent
      progress in the area. Current data strongly suggest that both PsO and PsA are T
      cell-mediated diseases, with a key role of various proinflammatory cytokines in
      their development. The involvement of T cells is highlighted by the superior
      efficacy of biologic therapies targeting T cell-derived proinflammatory cytokines
      in both diseases. Initially, PsO and PsA were thought to be Th1-mediated
      diseases; however, in the last years, several studies have shown the important
      role of other T cell subsets, including Th17, Th22, Th9 and Treg cells, in the
      pathogenesis of both diseases, which has led to the development of new therapies.

PMID- 27050732
TI  - Health and Social Security Needs of Rickshaw Pullers in Ranchi.
AB  - A significant number of "marginalized" population groups are denied their health
      rights, healthcare access, benefits of government health programs, and other
      health-related social security benefits. These population groups, particularly
      the rickshaw pullers of India, are vulnerable because of their poor social and
      economic status, migration history, lack of permanent settlements, lack of social
      capital, and so on. These reasons, coupled with other social-political reasons,
      lead to no or limited access to health services and poor health conditions. This
      study intends to explore and understand the context and health seeking behavior
      of rickshaw pullers in Ranchi, the capital city of Jharkhand state in India, with
      special reference to wider social determinants of health such as, access,
      affordability, and delivery of health services. The data was collected from 1,000
      rickshaw pullers from 40 "rickshaw garages" in Ranchi. The findings of the study
      show that rickshaw pullers can't afford to "attach" much importance to their
      health due to various reasons and suffer from a variety of occupational and other
      illnesses. The health conditions of the rickshaw pullers are affected by poverty,
      negligence, illiteracy, lack of awareness and unavailability of affordable,
      quality health services. These are only a symptom of the larger structural issues
      affecting health. The study suggests that rickshaw pullers, being a marginalized
      and excluded population group, require special health and social security
      programs that include safe, affordable, and accessible services along with a
      special focus on health education, behavior change, and promotion of appropriate
      health-seeking behavior.

PMID- 27050733
TI  - The correlation between pancreatic steatosis and metabolic syndrome in a Chinese
      population.
AB  - BACKGROUND: Type 2 diabetes mellitus, obesity and hepatic steatosis showed a
      strong correlation with metabolic syndrome. However, data on the influence of
      pancreatic steatosis on metabolic syndrome are lacking. OBJECTIVE: Our aim is to
      perform the prevalence of pancreatic steatosis in adults and its association with
      metabolic syndrome in a Chinese population. METHODS: This was a cross-sectional
      study, randomly selected. A total of 1190 health examination subjects were
      recruited. Pancreatic steatosis or hepatic steatosis was diagnosed via trans
      abdominal sonography. The clinical and metabolic parameters were compared between
      the two groups, and their associations with pancreatic steatosis were examined.
      RESULTS: The prevalence of pancreatic steatosis was 30.7%. The presence of
      pancreatic steatosis was significantly increased by age, gender, central obesity,
      hepatic steatosis, hypertriglyceridemia and hyperglycemia. In the logistic
      regression analysis, age (P < 0.05), central obesity (P < 0.01), diabetes (P <
      0.05), hypertriglyceridemia (P < 0.05) and hepatic steatosis (P < 0.01) were
      independently associated with pancreatic steatosis. The number of the parameters
      of the metabolic syndrome in pancreatic steatosis group was more than that in non
      pancreatic steatosis group [(2.5 +/- 1.1) vs (1.4 +/- 1.2)] (P < 0.01).
      CONCLUSION: The pancreatic steatosis is strongly associated with the parameters
      of metabolic syndrome, such as central obesity, diabetes, and hepatic steatosis.

PMID- 27050734
TI  - Lyotropic Liquid Crystalline Cubic Phases as Versatile Host Matrices for Membrane
      Bound Enzymes.
AB  - Lyotropic liquid crystalline cubic mesophases can function as host matrices for
      enzymes because of their biomimetic structural characteristics, optical
      transparency, and capability to coexist with water. This study demonstrates that
      the in meso immobilized membrane-bound enzyme d-fructose dehydrogenase (FDH)
      preserves its full activity, follows ideal Michaelis-Menten kinetics, and shows
      improved stability compared to its behavior in solution. Even after 5 days, the
      immobilized FDH retained its full activity in meso, whereas a model hydrophilic
      enzyme, horseradish peroxidase, maintained only 21% of its original activity. We
      reason that the lipidic bilayers in the three-dimensional structures of cubic
      mesophases provide an ideal environment for the reconstitution of a membrane
      bound enzyme. The preserved activity, long-term stability, and reusability
      demonstrate that these hybrid nanomaterials are ideal matrices for biosensing and
      biocatalytic fuel cell applications. 

PMID- 27050735
TI  - Early Conventional MRI for Prediction of Neurodevelopmental Impairment in
      Extremely-Low-Birth-Weight Infants.
AB  - BACKGROUND: Extremely-low-birth-weight (ELBW; <=1,000 g) infants are at high risk
      for neurodevelopmental impairments. Conventional brain MRI at term-equivalent age
      is increasingly used for prediction of outcomes. However, optimal prediction
      models remain to be determined, especially for cognitive outcomes. OBJECTIVE: The
      aim was to evaluate the accuracy of a data-driven MRI scoring system to predict
      neurodevelopmental impairments. METHODS: 122 ELBW infants had a brain MRI
      performed at term-equivalent age. Conventional MRI findings were scored with a
      standardized algorithm and tested using a multivariable regression model to
      predict neurodevelopmental impairment, defined as one or more of the following at
      18-24 months' corrected age: cerebral palsy, bilateral blindness, bilateral
      deafness requiring amplification, and/or cognitive/language delay. Results were
      compared with a commonly cited scoring system. RESULTS: In multivariable
      analyses, only moderate-to-severe gyral maturational delay was a significant
      predictor of overall neurodevelopmental impairment (OR: 12.6, 95% CI: 2.6, 62.0;
      p < 0.001). Moderate-to-severe gyral maturational delay also predicted cognitive
      delay, cognitive delay/death, and neurodevelopmental impairment/death. Diffuse
      cystic abnormality was a significant predictor of cerebral palsy (OR: 33.6, 95%
      CI: 4.9, 229.7; p < 0.001). These predictors exhibited high specificity (range:
      94-99%) but low sensitivity (30-67%) for the above outcomes. White or gray matter
      scores, determined using a commonly cited scoring system, did not show
      significant association with neurodevelopmental impairment. CONCLUSIONS: In our
      cohort, conventional MRI at term-equivalent age exhibited high specificity in
      predicting neurodevelopmental outcomes. However, sensitivity was suboptimal,
      suggesting additional clinical factors and biomarkers are needed to enable
      accurate prognostication.

PMID- 27050736
TI  - Using Nurse Practitioners to Optimize Patient Flow in a Pediatric Emergency
      Department.
AB  - OBJECTIVES: Using nurse practitioners (NPs) in pediatric emergency departments
      (PEDs) is commonplace in the United States, yet little is known on the impact of
      NPs on patient flow measures in these environments. This study quantifies the
      impact of NPs on 2 common measures of patient flow. METHODS: We conducted a
      retrospective cohort study using administrative data from an academic tertiary
      care PED. Mean shift length of stay (LOS) and the daily proportion of patients
      leaving without being seen (LWBS) by a clinician were compared between shifts
      with and without NPs on duty, matched for external variables affecting the level
      of activity in the department. Multivariate regression analyses were also
      conducted to further adjust for covariates such as the total number of PED care
      providers, patient acuity distribution, and total volume seen in the ED. RESULTS:
      Despite a slightly reduced total number of providers present on shifts with NPs
      on duty, a modest but statistically significant reduction in mean shift LOS (
      19.11 minutes [95% confidence interval (CI), -31.01 to -7.22]) and daily
      proportion of LWBS (-1.11% [95% CI, -1.97% to -0.26%]) was observed for shifts
      with NPs compared with shifts without NPs on duty. Regression analyses showed
      that incremental NPs on shift were associated with a decreased LOS (-18.76
      minutes [95% CI, -24.51 to -13.02]) as well as a reduced odds of LWBS (odds
      ratio, 0.56; 95% CI, 0.37-0.87). CONCLUSIONS: Nurse practitioners have a modest
      impact on patient flow measures in a PED and are a valuable resource to optimize
      patient flow.

PMID- 27050737
TI  - Pediatric Patient With Altered Mental Status and Hypoxemia: Case Report.
AB  - Childhood cases of myxedema coma are extremely rare. We report a case of a 5-year
      old girl transferred to a tertiary care pediatric emergency department with
      hypoxemia and altered mental status and diagnosed with severe hypothyroidism and
      myxedema coma in the setting of acute influenza infection. Although it is rare,
      myxedema coma must remain in the differential diagnosis for altered mental status
      and organ dysfunction in the pediatric population.

PMID- 27050738
TI  - Imaging for Suspected Appendicitis: Variation Between Academic and Private
      Practice Models.
AB  - BACKGROUND: Little is known regarding the effect of different emergency
      department (ED) practice models on computed tomography (CT) and ultrasound (US)
      utilization for suspected appendicitis in the ED and through the potential
      inpatient hospital stay. OBJECTIVES: Examination rates of CT and US for suspected
      appendicitis at 2 different pediatric EDs (PEDs) through hospital admission: an
      academic affiliated tertiary PED (site A) compared with a private practice
      tertiary care PED (site B). METHODS: All visits with the ICD-9 (International
      Classification of Diseases, Ninth Revision) chief complaint of abdominal pain
      were retrospectively examined from May 1, 2009, to February 21, 2012. Suspected
      appendicitis visits were defined as any visit with the chief complaint of
      abdominal pain where a complete blood cell count was obtained. Abdominal CT and
      US in the PED and during hospital admission were compared across the 2 sites.
      Return visits within 72 hours were evaluated for any missed appendicitis.
      RESULTS: Overall appendicitis rates were similar at both sites: site A, 4.7%;
      site B, 4.0%. The odds of having a CT scan performed during visits to the PED for
      abdominal pain were significantly higher at site B (odds ratio [OR], 3.19; 95%
      confidence interval [95% CI], 2.74-3.71), whereas the odds of having an US at
      site B were the opposite (OR, 0.34; 95% CI, 0.28-0.40). When evaluating only the
      admitted visits, the odds of having a CT were also greater at site B (OR, 2.32;
      95% CI, 1.86-2.94) and having an US were less (OR, 0.57; 95% CI, 0.44-0.73).
      CONCLUSIONS: In this study of 2 PEDs with differing practice models, we
      identified a dramatic difference in imaging utilization among patients with
      suspected appendicitis.

PMID- 27050739
TI  - Axillary and Tympanic Temperature Measurement in Children and Normal Values for
      Ages.
AB  - AIM: The aim of the study was define the normal values of tympanic and axillary
      body temperature in healthy children. METHODS: This observational cross-sectional
      study was performed in healthy children aged 0 to 17 years who visited the
      ambulatory general pediatric of Istanbul Medical Faculty. RESULTS: Of 1364
      children, 651 (47.7%) were girls and 713 were boys, the mean (SD, range) age was
      72.5 (53.6, 1-204) months. The mean (SD) axillary body temperature was 36.04
      degrees C (0.46 degrees C; minimum, 35.0 degrees C; maximum, 37.6 degrees C). The
      95th and 99th percentiles were 36.8 degrees C and 37.0 degrees C, respectively.
      The mean (SD) tympanic body temperature was 36.91 degrees C (0.46 degrees C;
      minimum, 35.15 degrees C; maximum, 37.9 degrees C). The 95th and 99th percentiles
      were 37.6 degrees C and 37.8 degrees C, respectively. There were statistically
      significant differences between sexes for only tympanic body temperatures. Both
      axillary and tympanic body temperatures were statistically higher in 0 to 2
      months compared with other age groups. For this age group, the 99th percentile
      was 37.5 degrees C for axillary and 37.85 degrees C for tympanic temperature.
      CONCLUSIONS: Axillary and tympanic body temperatures should be considered as
      fever when they are more than 37.0 degrees C and 37.8 degrees C, respectively.
      For 0 to 2 months, fever is 37.5 degrees C and 37.85 degrees C in axillary and
      tympanic temperatures, respectively.

PMID- 27050740
TI  - Marijuana Misadventures in Children: Exploration of a Dose-Response Relationship
      and Summary of Clinical Effects and Outcomes.
AB  - OBJECTIVES: This study aimed to explore a dose-response relationship of delta-9
      tetrahydrocannabinol (THC) in THC-naive children after unintentional acute
      exposure and compare clinical outcomes with non-naive children. METHODS: A
      retrospective review was performed on children aged 31 days to 20 years who
      presented to Children's Hospital Colorado for care related to acute THC toxicity.
      The children were divided into groups based on exposure: group 1 (THC naive) and
      group 2 (THC non-naive). RESULTS: A total of 38 children (age, 3.5 [3] years) met
      inclusion for group 1 and an equal number of children (age, 15.1 [3.9] years) met
      the criteria for comparison in group 2. Eight naive patients had documentation of
      estimated THC dose ingested (mean [SD], 7.13 [5.8] mg/kg; range, 2.9-19.5 mg/kg).
      A direct relationship between estimated oral THC dose, level of medical
      intervention required, and hospital disposition was observed. Lethargy/somnolence
      was more common in the naive group (84% vs. 26%, P < 0.0001) whereas problems in
      cognition, perception, and behavior were more common in the non-naive group (4%
      vs 11%, P = 0.01). The duration of clinical effect and length of hospital stay
      were longer in the naive group (19.3 vs 5.0 hours, P < 0.0001) and (0.73 vs 0.19
      days, P < 0.0001) respectively. CONCLUSIONS: There seems to be a direct
      relationship between the estimated oral THC dose (mg/kg), hospital disposition,
      and level of medical intervention required. Symptoms and duration of effects
      after THC exposure varied based on the route of exposure, age of patient, and
      history of previous THC experience.

PMID- 27050741
TI  - Application of spectroscopy (1HMRS) to assess liver metabolite concentrations in
      rats with intrauterine growth restriction.
AB  - OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) measurement of liver
      metabolism in intrauterine growth restriction rats has seldom been reported. This
      study investigated the application of 1H-MRS in assessing liver metabolism in
      newborn pups that experienced intrauterine growth restriction. METHODS: Intra
      uterine growth restriction was established by feeding rats low-protein diets
      during pregnancy. Newborn pups received conventional magnetic resonance imaging
      and 1H-MRS using a 3.0T whole body MR scanner at 3, 8 and 12 weeks post birth.
      RESULTS: The success rate of 1H-MRS was 83.33%. Significantly lower body weight,
      BMI and body length at 3 weeks as well as significantly lower body weight, BMI
      and waist circumference at 8 and 12 weeks were observed in newborn pups of IUGR
      rats compared with pups of control rats. Significant differences in ACho/H2O,
      ACr/H2O, AGlx/H2O and ALipid/H2O at 3 and 8 weeks as well as significant
      differences in ACr/H2O, ALipid/H2O and AGlx/H2O at 12 weeks were observed between
      pups of control rats and pups of IUGR rats. CONCLUSION: 1H-MRS allows noninvasive
      assessment of liver metabolism in the rat and demonstrated the poor liver
      development of rats that experienced IUGR.

PMID- 27050742
TI  - A new Secondary metabolites of the crinoid (Comanthina schlegeli) associated
      fungus Alternaria brassicae 93.
AB  - Fungus Alternaria brassicae 93 isolated from crinoid (Comanthina schlegeli),
      which was collected from the South China Sea. Six compounds were isolated from A.
      brassicae 93, including one new compound (1), along with five known compounds,
      ochratoxin A methyl ester (2), cis-4-hydroxym-ellein (3), (R)-7-hydroxymellein
      (4), trans-2-anhydromevalonic (5) and protocatechuic acid (6). Their structures
      were determined by spectroscopic methods and comparison with reported data.
      Cytotoxicity against two human cancer cell lines and antibacterial activity
      against twelve aquatic bacteria of compound 1 were also tested. 

PMID- 27050743
TI  - Wired.

PMID- 27050744
TI  - Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary
      Epithelial Cells Derived from Nasal Polyps.
AB  - INTRODUCTION: Chronic rhinosinusitis with nasal polyposis is an inflammatory
      disease that, although not directly linked to allergy, often displays a Th2
      skewed inflammation characterized by elevated local IgE and IL-5 levels. The
      nasal cavity is constantly exposed to bacteria and viruses that may trigger
      epithelial inflammatory responses. To gain more insight into mechanisms by which
      such a biased inflammation might arise, we have investigated the epithelial
      expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship
      to disease and microbial triggers. METHODS: Epithelial cells were obtained from
      polyp tissues of nasal polyposis patients and from inferior turbinates of non
      diseased controls. Cells were exposed to various TLR-specific triggers to study
      the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the
      potential regulatory mechanisms through the expression profile the transcription
      factors ATF-3, DUSP-1, EGR-1, and NFKB-1. RESULTS: The TLR3 agonist and viral
      analogue poly(I:C) induced TSLP mRNA 13.0 +/- 3.1 fold (p < 0.05) and protein
      expression by 12.1 +/- 2.3-fold (p < 0.05) higher in epithelium isolated from
      nasal polyposis patients than in epithelium form healthy controls. This enhanced
      induction of TSLP may be a consequence of a down-regulated expression of DUSP-1
      in polyp epithelium. CONCLUSION: The TLR3 induced expression of TSLP introduces a
      mechanism by which the Th2-skewed tissue environment might arise in nasal polyps
      and invites a further evaluation of the potential contribution of current or past
      viral infections to polyposis pathogenesis.

PMID- 27050745
TI  - Bromide oxidation by ferrate(VI): The formation of active bromine and bromate.
AB  - Ferrate (VI) (abbreviated as Fe(VI)) has long been considered as a green oxidant
      that does not produce any known hazardous byproducts. However, this work shows
      that Fe(VI) can slowly oxidize bromide forming active bromine (HOBr/OBr(-)) and
      bromate, and in natural waters total organic bromine (TOBr) can also be detected.
      Results showed that the highest levels of active bromine and bromate were formed
      at lower pHs and in the absence of phosphate. Hydrogen peroxide, which forms from
      the reaction of Fe(VI) and water, plays an essential role in suppressing bromate
      formation by reducing active bromine back to bromide. Fe(VI) decomposition
      products (assumed to be particulate phase Fe(III)) can catalyze the decomposition
      of hydrogen peroxide by Fe(VI). Phosphate had a substantial inhibiting effect on
      the formation of active bromine, but less so on bromate formation. The presence
      of the raw water matrix in natural water suppressed bromate formation. For a
      natural water spiked with 0.1 mg/L of bromide, the bromate and TOBr
      concentrations after Fe(VI) oxidation were below 3.0 and 15 MUg/L, respectively.
      No consistent trend regarding the effect of pH or buffer ions on TOBr formation
      was observed due to the competition between Fe(VI), hydrogen peroxide, and
      natural organic matter (NOM) for reaction with active bromine. Under
      environmentally relevant conditions, the formation of bromate and TOBr would not
      be a problem for Fe(VI) application as their concentration levels are quite low.

PMID- 27050747
TI  - Ru-catalysed C-H silylation of unprotected gramines, tryptamines and their
      congeners.
AB  - Selective Ru-catalysed C2-H silylation of heteroarenes is presented. The
      transformation works with or without directing group assistance and requires no
      protecting groups. Gramines and tryptamines may be converted efficiently whilst
      avoiding deleterious elimination side-reactions. Mechanistic studies reveal an
      unusual activation of the indole C4-H bond by an electron-rich metal. 

PMID- 27050746
TI  - Impaired Chloroplast Biogenesis in Immutans, an Arabidopsis Variegation Mutant,
      Modifies Developmental Programming, Cell Wall Composition and Resistance to
      Pseudomonas syringae.
AB  - The immutans (im) variegation mutation of Arabidopsis has green- and white-
      sectored leaves due to action of a nuclear recessive gene. IM codes for PTOX, a
      plastoquinol oxidase in plastid membranes. Previous studies have revealed that
      the green and white sectors develop into sources (green tissues) and sinks (white
      tissues) early in leaf development. In this report we focus on white sectors, and
      show that their transformation into effective sinks involves a sharp reduction in
      plastid number and size. Despite these reductions, cells in the white sectors
      have near-normal amounts of plastid RNA and protein, and surprisingly, a marked
      amplification of chloroplast DNA. The maintenance of protein synthesis capacity
      in the white sectors might poise plastids for their development into other
      plastid types. The green and white im sectors have different cell wall
      compositions: whereas cell walls in the green sectors resemble those in wild
      type, cell walls in the white sectors have reduced lignin and cellulose
      microfibrils, as well as alterations in galactomannans and the decoration of
      xyloglucan. These changes promote susceptibility to the pathogen Pseudomonas
      syringae. Enhanced susceptibility can also be explained by repressed expression
      of some, but not all, defense genes. We suggest that differences in morphology,
      physiology and biochemistry between the green and white sectors is caused by a
      reprogramming of leaf development that is coordinated, in part, by mechanisms of
      retrograde (plastid-to-nucleus) signaling, perhaps mediated by ROS. We conclude
      that variegation mutants offer a novel system to study leaf developmental
      programming, cell wall metabolism and host-pathogen interactions.

PMID- 27050748
TI  - Specific c-Jun target genes in malignant melanoma.
AB  - A fundamental event in the development and progression of malignant melanoma is
      the de-regulation of cancer-relevant transcription factors. We recently showed
      that c-Jun is a main regulator of melanoma progression and, thus, is the most
      important member of the AP-1 transcription factor family in this disease.
      Surprisingly, no cancer-related specific c-Jun target genes in melanoma were
      described in the literature, so far. Therefore, we focused on pre-existing ChIP
      Seq data (Encyclopedia of DNA Elements) of 3 different non-melanoma cell lines to
      screen direct c-Jun target genes. Here, a specific c-Jun antibody to
      immunoprecipitate the associated promoter DNA was used. Consequently, we
      identified 44 direct c-Jun targets and a detailed analysis of 6 selected genes
      confirmed their deregulation in malignant melanoma. The identified genes were
      differentially regulated comparing 4 melanoma cell lines and normal human
      melanocytes and we confirmed their c-Jun dependency. Direct interaction between c
      Jun and the promoter/enhancer regions of the identified genes was confirmed by us
      via ChIP experiments. Interestingly, we revealed that the direct regulation of
      target gene expression via c-Jun can be independent of the existence of the
      classical AP-1 (5'-TGA(C/G)TCA-3') consensus sequence allowing for the subsequent
      down- or up-regulation of the expression of these cancer-relevant genes. In
      summary, the results of this study indicate that c-Jun plays a crucial role in
      the development and progression of malignant melanoma via direct regulation of
      cancer-relevant target genes and that inhibition of direct c-Jun targets through
      inhibition of c-Jun is a potential novel therapeutic option for treatment of
      malignant melanoma.

PMID- 27050749
TI  - Theodor M Fliedner (1 October 1929-9 November 2015), transplant pioneer.

PMID- 27050750
TI  - Low-dose irradiation prior to bone marrow transplantation results in ATM
      activation and increased lethality in Atm-deficient mice.

PMID- 27050751
TI  - Generation of memory T cells for adoptive transfer using clinical-grade anti
      CD62L magnetic beads.

PMID- 27050753
TI  - Effects of Immigration During Adolescence on Mental Health and Social Well-Being.

PMID- 27050752
TI  - Incidence and Risk Factors for Severe Bacterial Infections in People Living with
      HIV. ANRS CO3 Aquitaine Cohort, 2000-2012.
AB  - Severe non-AIDS bacterial infections (SBI) are the leading cause of hospital
      admissions among people living with HIV (PLHIV) in industrialized countries. We
      aimed to estimate the incidence of SBI and their risk factors in a large
      prospective cohort of PLHIV patients over a 13-year period in France. Patients
      followed up in the ANRS CO3 Aquitaine cohort between 2000 and 2012 were eligible;
      SBI was defined as a clinical diagnosis associated with hospitalization of >=48
      hours or death. Survival analysis was conducted to identify risk factors for
      SBI.Total follow-up duration was 39,256 person-years [PY] (31,370 PY on
      antiretroviral treatment [ART]). The incidence of SBI decreased from 26.7/1000 PY
      [95% CI: 22.9-30.5] over the period 2000-2002 to 11.9/1000 PY [10.1-13.8] in 2009
      2012 (p <0.0001). Factors independently associated to increased risk of SBI were:
      plasma HIVRNA>50 copies/mL (Hazard Ratio [HR] = 5.1, 95% Confidence Interval: 4.2
      6.2), CD4 count <500 cells/mm3 and CD4/CD8 ratio <0.8 (with a dose-response
      relationship for both markers), history of cancer (HR = 1.4 [1.0-1.9]), AIDS
      stage (HR = 1.7 [1.3-2.1]) and HCV coinfection (HR = 1.4, [1.1-1.6]). HIV
      positive patients with diabetes were more prone to SBI (HR = 1.6 [0.9-2.6]).
      Incidence of SBI decreased over a 13-year period due to the improvement in the
      virological and immune status of PLHIV on ART. Risk factors for SBI include low
      CD4 count and detectable HIV RNA, but also CD4/CD8 ratio, HCV coinfection,
      history of cancer and diabetes, comorbid conditions that have been frequent among
      PLHIV in recent years. 

PMID- 27050755
TI  - New molecular data shed light on the global phylogeny and species limits of the
      Rhipicephalus sanguineus complex.
AB  - The Rhipicephalus sanguineus complex is a group of closely related tick species
      distributed all around the world. In this study, using mitochondrial 16S
      ribosomal DNA, new specimens of R sanguineus sensu lato from Turkey and
      Rhipicephalus camicasi from Kenya, were evaluated together with available
      sequences of this complex in GenBank. Our objectives were to delimit the complex,
      re-evaluate its global phylogeny and develop a reconstruction of its
      biogeographic history. Given Turkey's geographical location and its neighboring
      status within Africa, Asia and Europe, molecular information of R. sanguineus
      s.l. species from this region could have important implications both on a
      regional and global scale. Phylogenetic trees obtained with three methods
      (Bayesian, Maximum Likelihood and Maximum Parsimony) were highly similar and
      consensus trees gave the same branching patterns and similar node support values.
      A total of four different clades with up to 9 Operational Taxonomic Units formed
      strong monophyletic groups. Biogeographic reconstructions demonstrated the
      importance of populations in Middle East (Turkey) in the spread of the group from
      Europe to Africa and Asia. Data supported previous conclusions on the existence
      of two species of R. sanguineus s.l. in South America and the strong molecular
      similarity between R. camicasi and the so-called tropical lineage of R.
      sanguineus s.l. These results point to the need of a re-evaluation of most
      specimens designated as R. sanguineus s.l. in East Europe, Middle East, Africa
      and Asia after an adequate re-description of this taxon.

PMID- 27050754
TI  - Vincristine-induced bystander effect in human lymphocytes.
AB  - Bystander effect is a known radiobiological effect, widely described using
      ionizing radiations and which, more recently, has also been related to chemical
      mutagens. In this study, we aimed to assess whether or not a bystander response
      can be induced in cultured human peripheral lymphocytes by vincristine, a
      chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an
      alkylating agent already known to induce this response in human lymphoblastoid
      cells. Designing a modified ad hoc protocol for the cytokinesis blocked
      micronucleus (MN) assay, we detected the presence of a dose-dependent bystander
      response in untreated cultures receiving the conditioned medium (CM) from
      mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN
      frequencies, expressed as micronucleated binucleates, were: 13.5+/-1.41 at 6MUM,
      22+/-2.12 at 12MUM or 28.25+/-5.13 at 15MUM vs. a control value of 4.75+/-1.59.
      MN levels for VCR, expressed as micronucleated mononucleates were: 2.75+/-0.88 at
      0.0MUM, 27.25+/-2.30 at 0.4MUM, 46.25+/-1.94 at 0.8MUM, 98.25+/-7.25 at 1.6MUM.
      To verify that no mutagen residual was transferred to recipient cultures together
      with the CM, we evaluated MN levels in cultures receiving the medium immediately
      after three washings following the chemical treatment (unconditioned medium). We
      further confirmed these results using a cell-mixing approach where untreated
      lymphocytes were co-cultured with donor cells treated with an effect-inducing
      dose of MMC or VCR. A distinct production pattern of both reactive oxygen species
      and soluble mediator proteins by treated cells may account for the differences
      observed in the manifestation of the bystander effect induced by VCR. In fact, we
      observed an increased level of ROS, IL-32 and TGF-beta in the CM from VCR treated
      cultures, not present in MMC treated cultures.

PMID- 27050756
TI  - Production and quality of beef from young bulls fed diets supplemented with
      peanut cake.
AB  - Peanut cake is a biodiesel byproduct that has been tested as an alternative feed
      additive for use in cattle production. This study aimed to assess the importance
      of dietary peanut cake inclusion for young bull growth rate, beef production, and
      beef quality. In total, 32 Nellore young bulls individually housed in stalls with
      a mean initial body weight of 390+/-43.5kg were distributed in a completely
      randomized design for the experiment. The animals were fed Tifton 85 hay and one
      of four concentrate mixtures with 0, 33, 66 or 100% peanut cake instead of
      soybean meal. There was a linear reduction (P<0.05) in the slaughter weight and
      hot carcass weight and a quadratic effect (P<0.05) on the beef texture. No
      alterations occurred in the physicochemical characteristics of the longissimus
      thoracis; however, changes were observed (P<0.05) in the longissimus thoracis
      fatty acid profile. The replacement of soybean meal with peanut cake at levels up
      to 100% in the diet of feedlot-finished young bulls promotes a beneficial
      increase in the levels of PUFAs and the following nutraceutical compounds:
      conjugated linoleic acid (CLA) and Omega3 and Omega6 fatty acids. 

PMID- 27050757
TI  - Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes
      Inflammatory Response in T Cell-Mediated Murine Colitis.
AB  - Inflammatory bowel diseases (IBD) are associated with functional inhibition of
      epithelial Na+/H+ exchange. In mice, a selective disruption of NHE3 (Slc9a3), a
      major apical Na+/H+ exchanger, also promotes IBD-like symptoms and gut microbial
      dysbiosis. We hypothesized that disruption of Na+/H+ exchange is necessary for
      the development of dysbiosis, which promotes an exacerbated mucosal inflammatory
      response. Therefore, we performed a temporal analysis of gut microbiota
      composition, and mucosal immune response to adoptive T cell transfer was
      evaluated in Rag2-/- and NHE3-/-/Rag2-/- (DKO) mice with and without broad
      spectrum antibiotics. Microbiome (16S profiling), colonic histology, T cell and
      neutrophil infiltration, mucosal inflammatory tone, and epithelial permeability
      were analyzed. In adoptive T cell transfer colitis model, Slc9a3 status was the
      most significant determinant of gut microbial community. In DKO mice, NHE3
      deficiency and dysbiosis were associated with dramatically accelerated and
      exacerbated disease, with rapid body weight loss, increased mucosal T cell and
      neutrophil influx, increased mucosal cytokine expression, increased permeability,
      and expansion of CD25-FoxP3+ Tregs; this enhanced susceptibility was alleviated
      by oral broad-spectrum antibiotics. Based on these results and our previous work,
      we postulate that epithelial electrolyte homeostasis is an important modulator in
      the progression of colitis, acting through remodeling of the gut microbial
      community. 

PMID- 27050758
TI  - Patterns of failure and optimal radiotherapy target volumes in primary intradural
      extramedullary Ewing sarcoma.

PMID- 27050759
TI  - Neuropathologic, phenotypic and functional analyses of Mucosal Associated
      Invariant T cells in Multiple Sclerosis.
AB  - BACKGROUND: The involvement of Mucosal Associated Invariant T (MAIT) cells, which
      are anti-microbial semi-invariant T cells, remains elusive in Multiple Sclerosis
      (MS). OBJECTIVE: Deciphering the potential involvement of MAIT cells in the MS
      inflammatory process. METHODS: By flow cytometry, blood MAIT cells from similar
      cohorts of MS patients and healthy volunteers (HV) were compared for frequency,
      phenotype, activation potential after in vitro TCR engagement by bacterial
      ligands and transmigration abilities through an in vitro model of blood-brain
      barrier. MS CNS samples were also studied by immunofluorescent staining and
      quantitative PCR. RESULTS AND CONCLUSION: Blood MAIT cells from relapsing
      remitting MS patients and HV presented similar frequency, ex vivo effector
      phenotype and activation abilities. MAIT cells represented 0.5% of the total
      infiltrating T cells on 39 MS CNS lesions. This is low as compared to blood
      frequency (p<0.001), but consistent with their low transmigration rate. Finally,
      transcriptional over-expression of MR1 - which presents cognate antigens to MAIT
      cells - and of the activating cytokines IL-18 and IL-23 was evidenced in MS
      lesions, suggesting that the CNS microenvironment is suited to activate the few
      infiltrating MAIT cells. Taken together, these data place MAIT cells from MS
      patients as minor components of the inflammatory pathological process.

PMID- 27050760
TI  - An Examination of the Structure and Construct Validity of the Wender Utah Rating
      Scale.
AB  - The Wender Utah Rating Scale (Ward, Wender, & Reimherr, 1993 ) has been widely
      used in adult attention-deficit/hyperactivity disorder (ADHD) research to assess
      childhood symptoms retrospectively, but little research has examined its factor
      structure and specificity in predicting ADHD versus other psychopathology.
      Consequently, this study had 2 goals: (a) to examine the Wender Utah Rating
      Scale's structure, and (b) to explicate the construct validity of this measure by
      relating factors from our structural analyses to other ADHD, psychopathology, and
      personality measures. Structural analyses in an adult community sample (N = 294)
      yielded a 3-factor structure of aggression (e.g., angry), internalizing distress
      (e.g., depressed), and academic difficulties (e.g., underachiever). Correlational
      and regression analyses indicated that these factors failed to display
      specificity in their associations with ADHD versus other psychopathology.
      Aggression and internalizing distress associated most strongly with indicators of
      externalizing (e.g., ill temper, manipulativeness) and internalizing
      psychopathology (e.g., depression, anxiety), respectively. Academic difficulties
      associated most strongly with ADHD symptoms, but these relations were relatively
      weak. Taken together, these findings raise concerns about the Wender Utah Rating
      Scale's construct validity, although additional longitudinal research is needed
      to clarify to what extent the Wender Utah Rating Scale validly assesses childhood
      ADHD symptoms.

PMID- 27050762
TI  - Digesting the Expanding Mechanisms of Autophagy.
AB  - Autophagy is a catabolic 'self-eating' pathway that is emerging as a crucial
      integration point in cell physiology. With its own set of genes, the autophagy
      pathway communicates with virtually all signalling networks and organelles.
      Recent advances have been made in understanding the origin of the autophagosomal
      membrane, novel regulators, and the mechanisms by which specific intracellular
      membranes become autophagy substrates. New studies on noncanonical autophagy,
      mediated by subsets of autophagy proteins, and the role of autophagy proteins in
      non-autophagy pathways are also emerging in many different biological contexts.
      Our understanding of canonical autophagy, including membrane origin and autophagy
      proteins, needs to be considered together with emerging noncanonical pathways.

PMID- 27050761
TI  - Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7
      in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release.
AB  - Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is
      a key molecular determinant of pain sensation. However, defining the Nav1.7
      contribution to nociceptive signalling has been hampered by a lack of selective
      inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7
      inhibitors; PF-05198007 and PF-05089771, which we have used to directly
      interrogate Nav1.7's role in nociceptor physiology. We report that Nav1.7 is the
      predominant functional TTX-sensitive Nav in mouse and human nociceptors and
      contributes to the initiation and the upstroke phase of the nociceptor action
      potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic
      transmission in the dorsal horn of the spinal cord as well as peripheral
      neuropeptide release in the skin. These findings demonstrate multiple
      contributions of Nav1.7 to nociceptor signalling and shed new light on the
      relative functional contribution of this channel to peripheral and central
      noxious signal transmission. 

PMID- 27050763
TI  - Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic
      Lupus Erythematosus-Like Disease of BXSB.Yaa Mice.
AB  - IL6 is a multifunctional cytokine that drives terminal B cell differentiation and
      secretion of immunoglobulins. IL6 also cooperates with IL21 to promote
      differentiation of CD4+ T follicular helper cells (TFH). Elevated serum levels of
      IL6 correlate with disease flares in patients with systemic lupus erythematosus
      (SLE). We previously reported that IL21 produced by TFH plays a critical role in
      the development of the SLE-like disease of BXSB.Yaa mice. To examine the possible
      contributions of IL6 to disease, we compared disease parameters in IL6-deficient
      and IL6-competent BXSB.Yaa mice. We report that survival of IL6-deficient
      BXSB.Yaa mice was significantly prolonged in association with significant
      reductions in a variety of autoimmune manifestations. Moreover, B cells
      stimulated by co-engagement of TLR7 and B cell receptor (BCR) produced high
      levels of IL6 that was further augmented by stimulation with Type I interferon
      (IFN1). Importantly, the frequencies of TFH and serum levels of IL21 were
      significantly reduced in IL6-deficient mice. These findings suggest that high
      level production of IL6 by B cells induced by integrated signaling from the IFN1
      receptor, TLR7 and BCR promotes the differentiation of IL21-secreting TFH in a
      signaling sequence that drives the lethal autoimmune disease of BXSB.Yaa mice. 

PMID- 27050764
TI  - PTPN22 is not associated with Behcet's disease. Study spanning the complete gene
      region in the Spanish population and meta-analysis of the functional variant
      R620W.
AB  - OBJECTIVES: The functional variant R620W of the protein tyrosine phosphatase non
      receptor-22 (PTPN22) gene plays an important role in susceptibility to several
      immuno-mediated pathologies. Behcet's disease (BD) is a complex disease related
      to the immune system with a demonstrated genetic base. The HLA class I genes are
      the most important genetic factors in BD although other genes are also involved
      in the susceptibility to this disease. The PTPN22 has been proposed as a
      candidate gene in BD but this association has not been clearly demonstrated yet.
      The aim of this study was to assess the association of PTPN22 with BD. METHODS: A
      cohort composed of 404 Spanish BD patients and 1517 unrelated healthy individuals
      ethnically matched was genotyped in rs2476601 (R620W). Five tag SNPs: rs1217412,
      rs2476599, rs3789607, rs3765598 and rs1217419 (spanning a 57 Kb region between
      3'UTR and 5'UTR) and rs2488457 (located at the promoter region) were also studied
      in order to perform a screening of the complete gene. Genotyping was performed
      using TaqMan(r) assays. The rs2476601 data were included in a meta-analysis
      together with those published till the date. The rest of SNPs were used in a case
      control study. RESULTS: No evidence of the association of rs2476601 with BD in
      the meta-analysis (P = 0.504 in the model of alleles) was found. In the case
      control study, no statistically significant differences were observed when
      comparing the distribution of variants in patients and controls. CONCLUSIONS: Our
      results do not support a major role of the PTPN22 gene in BD.

PMID- 27050766
TI  - Design and Synthesis of Heteroleptic Cyclometalated Iridium(III) Complexes
      Containing Quinoline-Type Ligands that Exhibit Dual Phosphorescence.
AB  - The design and synthesis of some cyclometalated iridium(III) complexes containing
      quinoline-type ligands as ancillary ligands are reported. The emission spectra of
      Ir(III) complexes containing a quinolinolate (6, 8, 10) moiety exhibit a single
      emission peak at ca. 590 nm, resulting in a red colored emission. However,
      Ir(III) complexes containing 8-sulfonamidoquinoline ligands (11, 13-21) exhibit
      two different emission peaks (dual emission) at ca. 500 nm and ca. 600 nm upon
      excitation at 366 nm, resulting in a red-colored emission for 11 and a pale
      yellow-colored emission for 14-18 at 298 K. Especially, a white emission was
      observed for 19 at 298 and 77 K in dimethyl sulfoxide. The mechanistic studies
      based on time-dependent density functional theory calculations and time-resolved
      emission spectroscopy suggest that this dual emission originates from two
      independent emission states. 

PMID- 27050765
TI  - Trim69 regulates zebrafish brain development by ap-1 pathway.
AB  - Proteins belonging to the TRIM family have been implicated in a variety of
      cellular processes such as apoptosis, differentiation, neurogenesis, muscular
      physiology and innate immune responses. Trim69, previously identified as a novel
      gene cloned from a human testis cDNA library, has a homologous gene in zebrafish
      and this study focused on investigating the function of trim69 in zebrafish
      neurogenesis. Trim69 was found to be expressed in zebrafish embryo brain at the
      early stages. Knockdown of trim69 led to deformed brain development, obvious
      signs of apoptosis present in the head, and decreased expression of neuronal
      differentiation and stem cell markers. This phenotype was rescued upon co
      injection of human mRNA together along with the trim69 knockdown. Results of this
      study also showed an interaction between TRIM69 and c-Jun in human cells, and
      upon TRIM69 knock down c-Jun expression subsequently increased, whereas the over
      expression of TRIM69 led to the down-regulation of c-Jun. Additionally, knockdown
      both c-Jun and trim69 can rescue the deformed brain, evident cellular apoptosis
      in the head and decreased expression of neuronal differentiation and stem cell
      markers. Overall, our results support a role for trim69 in the development of the
      zebrafish brain through ap-1 pathway. 

PMID- 27050767
TI  - Docking and Scoring with Target-Specific Pose Classifier Succeeds in Native-Like
      Pose Identification But Not Binding Affinity Prediction in the CSAR 2014
      Benchmark Exercise.
AB  - The CSAR 2014 exercise provided an important benchmark for testing current
      approaches for pose identification and ligand ranking using three X-ray
      characterized proteins: Factor Xa (FXa), Spleen Tyrosine Kinase (SYK), and tRNA
      Methyltransferase (TRMD). In Phase 1 of the exercise, we employed Glide and
      MedusaDock docking software, both individually and in combination, with the
      special target-specific pose classifier trained to discriminate native-like from
      decoy poses. All approaches succeeded in the accurate detection of native and
      native-like poses. We then used Glide SP and MedusaScore scoring functions
      individually and in combination with the pose-scoring approach to predict
      relative binding affinities of the congeneric series of ligands in Phase 2 of the
      exercise. Similar to other participants in the CSAR 2014 exercise, we found that
      our models showed modest prediction accuracy. Quantitative structure-activity
      relationship (QSAR) models developed for the FXa ligands using available
      bioactivity data from ChEMBL showed relatively low prediction accuracy for the
      CSAR 2014 ligands of the same target. Interestingly, QSAR models built with CSAR
      data only yielded Spearman correlation coefficients as high as rho = 0.69 for FXa
      and rho = 0.79 for SYK based on 5-fold cross-validation. Virtual screening of the
      DUD library using the FXa structure was successful in discriminating between
      active compounds and decoys in spite of poor ranking accuracy of the underlying
      scoring functions. Our results suggest that two of the three common tasks
      associated with molecular docking, i.e., native-like pose identification and
      virtual screening, but not binding affinity prediction, could be accomplished
      successfully for the CSAR 2014 challenge data set.

PMID- 27050768
TI  - The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of
      ATDC5 Progenitor Cells.
AB  - OBJECTIVES: NSAIDs are used to relieve pain and decrease inflammation by
      inhibition of cyclooxygenase (COX)-catalyzed prostaglandin (PG) synthesis. PGs
      are fatty acid mediators involved in cartilage homeostasis, however the action of
      their synthesizing COX-enzymes in cartilage differentiation is not well
      understood. In this study we hypothesized that COX-1 and COX-2 have differential
      roles in chondrogenic differentiation. METHODS: ATDC5 cells were differentiated
      in the presence of COX-1 (SC-560, Mofezolac) or COX-2 (NS398, Celecoxib) specific
      inhibitors. Specificity of the NSAIDs and inhibition of specific prostaglandin
      levels were determined by EIA. Prostaglandins were added during the
      differentiation process. Chondrogenic outcome was determined by gene- and protein
      expression analyses. RESULTS: Inhibition of COX-1 prevented Col2a1 and Col10a1
      expression. Inhibition of COX-2 resulted in decreased Col10a1 expression, while
      Col2a1 remained unaffected. To explain this difference expression patterns of
      both COX-enzymes as well as specific prostaglandin concentrations were
      determined. Both COX-enzymes are upregulated during late chondrogenic
      differentiation, whereas only COX-2 is briefly expressed also early in
      differentiation. PGD2 and PGE2 followed the COX-2 expression pattern, whereas
      PGF2alpha and TXA2 levels remained low. Furthermore, COX inhibition resulted in
      decreased levels of all tested PGs, except for PGD2 and PGF2alpha in the COX-1
      inhibited condition. Addition of PGE2 and PGF2alpha resulted in increased
      expression of chondrogenic markers, whereas TXA2 increased expression of
      hypertrophic markers. CONCLUSIONS: Our findings point towards a differential role
      for COX-enzymes and PG-production in chondrogenic differentiation of ATDC5 cells.
      Ongoing research is focusing on further elucidating the functional partition of
      cyclooxygenases and specific prostaglandin production.

PMID- 27050769
TI  - A Novel Approach to Global Benchmarking of Risk-Adjusted Surgical Outcomes:
      Beyond Perioperative Mortality Rate.

PMID- 27050770
TI  - Evidence of a metacognitive benefit to memory?
AB  - Studies of the memory-control framework have contrasted free-report and forced
      report recall, with little regard to the order of these two tests. The present
      experiment sought to demonstrate that test order is crucial, and that this
      suggests a potential role for metacognitive monitoring on memory retrieval.
      Participants undertook tests of episodic and semantic memory in both free- and
      forced-report format, in one of the two potential response orders. This showed
      that free-report performance was more accurate if conducted prior to forced
      report, rather than after it, with no cost to memory quantity. Additionally,
      there was a trend towards higher forced-report performance if it was preceded by
      an initial free-report test, a pattern revealed by a meta-analysis to be
      consistent with previous studies in the literature. These findings suggest a
      reciprocal relationship between metacognitive monitoring and early retrieval
      processes in memory that results in higher memory performance when monitoring is
      encouraged.

PMID- 27050771
TI  - Surfactant-Free Assembly of Mesoporous Carbon Hollow Spheres with Large Tunable
      Pore Sizes.
AB  - Mesoporous carbon hollow spheres (MCHS) have wide applications, including
      catalysis, absorption, and energy storage/conversion. Herein, we report a one
      pot, surfactant-free synthesis of MCHS using three molecules: resorcinol,
      formaldehyde, and tetrapropyl orthosilicate. The co-condensation process between
      the in situ generated silica primary particles and the polymer oligomers is
      regulated, leading to monodispersed MCHS with adjustable pore sizes from
      micropores to 13.9 nm. The resultant MCHS shows excellent performance for
      electrochemical double-layer capacitors with high capacitance (310 F g(-1) at 1 A
      g(-1)), excellent rate capability (157 F g(-1) at 50 A g(-1)), and outstanding
      cycling stability (98.6% capacity retention after 10 000 cycles at 10 A g(-1)).
      Our one-pot synthesis strategy is versatile and can be extended to fabricate
      metal oxide@mesoporous carbon yolk-shell structures in the absence of surfactant,
      paving the way toward designed synthesis of nanostructured mesoporous carbon
      composites for various applications.

PMID- 27050772
TI  - Determination of neonicotinoids in Estonian honey by liquid chromatography
      electrospray mass spectrometry.
AB  - The aim of the study was to provide a comprehensive overview of neonicotinoid
      pesticide residues in honey samples for a single country and compare the results
      with the import data for neonicotinoid pesticides. The levels of four
      neonicotinoid pesticides, namely thiamethoxam, imidacloprid, acetamiprid, and
      thiacloprid, were determined in 294 honey samples harvested from 2005 to 2013
      from more than 200 locations in Estonia. For the analyzed honey samples, 27%
      contained thiacloprid, and its levels in all cases were below the maximum residue
      level set by the European Union. The other neonicotinoids were not detected. The
      proportion of thiacloprid-positive samples for different years correlates well
      with the data on thiacloprid imports into Estonia, indicating that honey
      contamination with neonicotinoids can be estimated based on the import data. 

PMID- 27050773
TI  - Reflectance Measures from Infant Ears With Normal Hearing and Transient
      Conductive Hearing Loss.
AB  - OBJECTIVE: The objective is to develop methods to utilize newborn reflectance
      measures for the identification of middle-ear transient conditions (e.g., middle
      ear fluid) during the newborn period and ultimately during the first few months
      of life. Transient middle-ear conditions are a suspected source of failure to
      pass a newborn hearing screening. The ability to identify a conductive loss
      during the screening procedure could enable the referred ear to be either (1)
      cleared of a middle-ear condition and recommended for more extensive hearing
      assessment as soon as possible, or (2) suspected of a transient middle-ear
      condition, and if desired, be rescreened before more extensive hearing
      assessment. DESIGN: Reflectance measurements are reported from full-term,
      healthy, newborn babies in which one ear referred and one ear passed an initial
      auditory brainstem response newborn hearing screening and a subsequent distortion
      product otoacoustic emission screening on the same day. These same subjects
      returned for a detailed follow-up evaluation at age 1 month (range 14 to 35
      days). In total, measurements were made on 30 subjects who had a unilateral refer
      near birth (during their first 2 days of life) and bilateral normal hearing at
      follow-up (about 1 month old). Three specific comparisons were made: (1)
      Association of ear's state with power reflectance near birth (referred versus
      passed ear), (2) Changes in power reflectance of normal ears between newborn and
      1 month old (maturation effects), and (3) Association of ear's newborn state
      (referred versus passed) with ear's power reflectance at 1 month. In addition to
      these measurements, a set of preliminary data selection criteria were developed
      to ensure that analyzed data were not corrupted by acoustic leaks and other
      measurement problems. RESULTS: Within 2 days of birth, the power reflectance
      measured in newborn ears with transient middle-ear conditions (referred newborn
      hearing screening and passed hearing assessment at age 1 month) was significantly
      greater than power reflectance on newborn ears that passed the newborn hearing
      screening across all frequencies (500 to 6000 Hz). Changes in power reflectance
      in normal ears from newborn to 1 month appear in approximately the 2000 to 5000
      Hz range but are not present at other frequencies. The power reflectance at age 1
      month does not depend significantly on the ear's state near birth (refer or pass
      hearing screening) for frequencies above 700 Hz; there might be small differences
      at lower frequencies. CONCLUSIONS: Power reflectance measurements are
      significantly different for ears that pass newborn hearing screening and ears
      that refer with middle-ear transient conditions. At age 1 month, about 90% of
      ears that referred at birth passed an auditory brainstem response hearing
      evaluation; within these ears the power reflectance at 1 month did not differ
      between the ear that initially referred at birth and the ear that passed the
      hearing screening at birth for frequencies above 700 Hz. This study also proposes
      a preliminary set of criteria for determining when reflectance measures on young
      babies are corrupted by acoustic leaks, probes against the ear canal, or other
      measurement problems. Specifically proposed are "data selection criteria" that
      depend on the power reflectance, impedance magnitude, and impedance angle.
      Additional data collected in the future are needed to improve and test these
      proposed criteria.

PMID- 27050774
TI  - Selective Vulnerability of Cancer Cells by Inhibition of Ca(2+) Transfer from
      Endoplasmic Reticulum to Mitochondria.

PMID- 27050775
TI  - Listening to the voices of Latina women: Sexual and reproductive health
      intervention needs and priorities in a new settlement state in the United States.
AB  - Latina women in the United States are disproportionately affected by negative
      sexual and reproductive health outcomes. Our community-based participatory
      research partnership conducted in-depth interviews exploring sexual and
      reproductive health needs and priorities with 25 Latinas in North Carolina and
      identified themes through constant comparison, a grounded theory development
      approach. Participants described individual-, interpersonal-, and clinic-level
      factors affecting their sexual and reproductive health as well as potentially
      successful intervention characteristics. Our findings can be used to inform
      culturally congruent interventions to reduce sexual and reproductive health
      disparities among Latinas, particularly in new settlement states in the
      southeastern United States.

PMID- 27050776
TI  - Lesbian, gay, & bisexual older adults: linking internal minority stressors,
      chronic health conditions, and depression.
AB  - OBJECTIVES: This study aims to: (1) test whether the minority stressors
      disclosure of sexual orientation; and (2) internalized heterosexism are
      predictive of chronic physical health conditions; and (3) depression; (4) to test
      direct and indirect relationships between these variables; and (5) whether
      chronic physical health conditions are further predictive of depression, net of
      disclosure of sexual orientation and internalized heterosexism. METHODS:
      Secondary analysis of national, community-based surveys of 2349 lesbian, gay, and
      bisexual adults aged 50 and older residing in the US utilizing structural
      equation modeling. RESULTS: Congruent with minority stress theory, disclosure of
      sexual orientation is indirectly associated with chronic physical health
      conditions and depression, mediated by internalized heterosexism with a
      suppressor effect. Internalized heterosexism is directly associated with chronic
      physical health conditions and depression, and further indirectly associated with
      depression mediated by chronic physical health conditions. Finally, chronic
      physical health conditions have an additional direct relationship with
      depression, net of other predictor variables. CONCLUSION: Minority stressors and
      chronic physical health conditions independently and collectively predict
      depression, possibly a synergistic effect. Implications for depression among
      older sexual minority adults are discussed.

PMID- 27050777
TI  - Clinical and Surgical Factors Associated With Increased Epilepsy Risk in Children
      With Hydrocephalus.
AB  - BACKGROUND: Children with hydrocephalus are at risk for epilepsy both due to
      their underlying condition and as a consequence of surgical treatment; however,
      the relative contributions of these factors remain unknown. OBJECTIVE: The
      authors sought to characterize epilepsy among children with infancy-onset
      hydrocephalus and to examine the risks of epilepsy associated with hydrocephalus
      subtype and with factors related to surgical treatment. METHODS: We conducted a
      longitudinal cohort study of all children with infancy-onset hydrocephalus
      treated at a major regional children's hospital during 2002 to 2012, with follow
      up to ascertain risk factors and epilepsy outcome through April 2015. Poisson
      regression was used to calculate adjusted risk ratios and 95% confidence
      intervals for associations. RESULTS: Among 379 children with hydrocephalus, 86
      (23%) developed epilepsy (mean onset age = 2.7 years), almost one fifth of whom
      had a history of infantile spasms. Relative to spina bifida-associated
      hydrocephalus, children with other major hydrocephalus subtypes had fourfold
      higher risks of developing epilepsy. Among children who underwent surgery,
      surgical infection doubled the risk of epilepsy (risk ratio = 2.0, 95% confidence
      interval = 1.4 to 3.0). Epilepsy was associated with surgical failure for
      intracranial reasons but not extracranial reasons (risk ratio = 1.7, 95%
      confidence interval = 1.1 to 2.7; risk ratio = 1.1, 95% confidence interval = 0.7
      to 1.9, respectively). CONCLUSIONS: Epilepsy is common among children with
      hydrocephalus. Compared with children with spina bifida-associated hydrocephalus,
      children with other major hydrocephalus subtypes have a markedly increased risk
      of epilepsy. Surgical infection doubles the risk of epilepsy.

PMID- 27050778
TI  - Trait and gender differences in personality: implications for GP training and
      future research.

PMID- 27050779
TI  - Diastereoselective Cascade Assembly of Functionalized Pyrano[3,4-c]pyrrole
      Derivatives.
AB  - A novel convenient approach for the synthesis of densely functionalized
      pyrano[3,4-c]pyrrole derivatives was developed. Cascade transformation of the
      simple adducts of tetracyanoethylene (TCNE) and ketones (4-oxoalkane-1,1,2,2
      tetracarbonitriles) in the presence of aldehyde under the action of acetic acid
      led to the diastereoselective formation of targeted pyrano[3,4-c]pyrroles. The
      reaction pathway was thoroughly investigated, and proposed intermediates were
      shown to be consistent with experiment. 

PMID- 27050780
TI  - Versatile surface engineering of porous nanomaterials with bioinspired polyphenol
      coatings for targeted and controlled drug delivery.
AB  - The development of biocompatible drug delivery systems with targeted recognition
      and controlled release has experienced a number of design challenges, including,
      for example, complicated preparation steps and premature drug release. Herein, we
      address these problems through an in situ self-polymerization method that
      synthesizes biodegradable polyphenol-coated porous nanomaterials for targeted and
      controlled drug delivery. As a proof of concept, we synthesized polyphenol-coated
      mesoporous silica nanoparticles, termed MSN@polyphenol. The polyphenol coatings
      not only improved colloidal stability and prevented premature drug leakage, but
      also provided a scaffold for immobilization of targeting moieties, such as
      aptamers. Both immobilization of targeting aptamers and synthesis of polyphenol
      coating are easily accomplished without the aid of any other organic reagents.
      Importantly, the polyphenol coating (EGCg) used in this study could be
      biodegraded by acidic pH and intracellular glutathione, resulting in the release
      of trapped anticancer drugs. Based on confocal fluorescence microscopy and
      cytotoxicity experiments, drug-loaded and polyphenol-coated MSNs were shown to
      possess highly efficient internalization and an apparent cytotoxic effect on
      target cancer, but not control, cells. Our results suggest that these highly
      biocompatible and biodegradable polyphenol-coated MSNs are promising vectors for
      controlled-release biomedical applications and cancer therapy. 

PMID- 27050781
TI  - Rationale of hyperthermia for radio(chemo)therapy and immune responses in
      patients with bladder cancer: Biological concepts, clinical data,
      interdisciplinary treatment decisions and biological tumour imaging.
AB  - Bladder cancer, the most common tumour of the urinary tract, ranks fifth among
      all tumour entities. While local treatment or intravesical instillation of
      bacillus Calmette-Guerin (BCG) provides a treatment option for non-muscle
      invasive bladder cancer of low grade, surgery or radio(chemo)therapy (RT) are
      frequently applied in high grade tumours. It remains a matter of debate whether
      surgery or RT is superior with respect to clinical outcome and quality of life.
      Surgical resection of bladder cancer can be limited by acute side effects,
      whereas, RT, which offers a non-invasive treatment option with organ- and
      functional conservation, can cause long-term side effects. Bladder toxicity by RT
      mainly depends on the total irradiation dose, fraction size and tumour volume.
      Therefore, novel approaches are needed to improve clinical outcome. Local tumour
      hyperthermia is currently used either as an ablation therapy or in combination
      with RT to enhance anti-tumour effects. In combination with RT an increase of the
      temperature in the bladder stimulates the local blood flow and as a result can
      improve the oxygenation state of the tumour, which in turn enhances radiation
      induced DNA damage and drug toxicity. Hyperthermia at high temperatures can also
      directly kill cells, particularly in tumour areas which are poorly perfused,
      hypoxic or have a low tissue pH. This review summarises current knowledge
      relating to the role of hyperthermia in RT to treat bladder cancer, the induction
      and manifestation of immunological responses induced by hyperthermia, and the
      utilisation of the stress proteins as tumour-specific targets for tumour
      detection and monitoring of therapeutic outcome.

PMID- 27050782
TI  - Lead Optimization of 2-Phenylindolylglyoxylyldipeptide Murine Double Minute
      (MDM)2/Translocator Protein (TSPO) Dual Inhibitors for the Treatment of Gliomas.
AB  - In glioblastoma multiforme (GBM), translocator protein (TSPO) and murine double
      minute (MDM)2/p53 complex represent two druggable targets. We recently reported
      the first dual binder 3 possessing a higher anticancer effect in GBM cells than
      the standards PK11195 1 or Nutlin-3 2 singularly applied. Herein, through a
      structure-activity relationship study, we developed derivatives 4-10 with
      improved potencies toward both TSPO and MDM2. As a result, compound 9: (i)
      reactivated the p53 functionality; (ii) inhibited the viability of two human GBM
      cells; (iii) impaired the proliferation of glioma cancer stem cells (CSCs), more
      resistant to chemotherapeutics and responsible of GBM recurrence; (iv) sensitized
      GBM cells and CSCs to the activity of temozolomide; (v) directed its effects
      preferentially toward tumor cells with respect to healthy ones. Thus, 9 may
      represent a promising cytotoxic agent, which is worthy of being further developed
      for a therapeutic approach against GBM, where the downstream p53 signaling is
      intact and TSPO is overexpressed.

PMID- 27050783
TI  - The Incidence and Evolution of Parkinsonian Rigidity in Rett Syndrome: A Pilot
      Study.
AB  - BACKGROUND: Patients with Rett syndrome (RTT) may demonstrate parkinsonian
      features. Here, we report a preliminary cross-sectional and prospective
      evaluation of the evolution, regional distribution, and eventual incidence of
      rigid tone in a cohort of MECP2 mutation-positive patients. METHODS: In 51
      participants, muscle tone rigidity in extremity regions and neck plus hypomimia
      were quantified using an RTT rigidity distribution (RTTRD) score with a range of
      0 to 15. RTTRD scores were correlated with age, ability to walk and speak,
      mutation type, and, in a small subgroup (n=9), cerebrospinal fluid (CSF)
      homovanillic acid (HVA) and 5-hydroxyindole-acetic acid levels. RESULTS:
      Participant ages ranged from 2 years and 5 months, to 54 years. Rigidity was
      found in 43/51 (84.3%); it appeared as early as age 3, increased in extent with
      age, and was present in all participants aged >=13. Ankle region rigidity
      appeared first, followed by proximal legs, arms, neck, and face. Ambulatory
      participants (n=21) had lower RTTRD scores than nonambulatory (n=30; p=0.003). We
      found a trend to lower scores in participants with retained speech (n=13) versus
      those with none (n=38; p=0.074), and no difference in scores for those with
      truncating (n=25) versus missense mutations (n=22; p=0.387). RTTRD scores
      correlated negatively with CSF HVA levels (R=-0.83; p=0.005), but not with 5
      hydroxyindole-acetic acid levels (R=-0.45; p=0.22). CONCLUSIONS: Although
      assessment of muscle tone is somewhat subjective and the RTTRD has not been
      validated, this study nevertheless suggests that parkinsonian rigidity in RTT is
      common and frequently increases in extent with age; its severity correlates
      directly with impaired ambulation and inversely with CSF HVA levels.

PMID- 27050784
TI  - Endoplasmic reticulum stress and renal lesion in mice with combination of high
      fat diet and streptozotocin-induced diabetes.
AB  - PURPOSE: To investigate in the kidney the pathologic changes and expression of
      GRP78 and CHOP in the Kunming (KM) mice with combination of high-fat diet and
      streptozotocin-induced diabetes. METHODS: Sixty two male KM mice were randomly
      divided into a normal control (NC) group (n=20) and a high-fat diet (HFD) group
      (n=42). After a four-week dietary manipulation, the KM mice in the HFD group were
      injected intraperitoneally with streptozotocin to induce diabetes. After diabetic
      models were successfully established, the kidneys were excised and conserved for
      further test. RESULTS: No significant difference in the body weight was observed
      after the dietary manipulation (p=0.554). After the streptozotocin was injected,
      fasting blood glucose levels in the diabetes group (DM) were significantly higher
      than that in the NC group (p<0.0001). Glomerular atrophy observed under light
      microscope in the DM group was more serious compared with the NC group. The
      expression of GRP78 and CHOP in the kidneys of the mice in the DM group were
      higher compared with the NC group. CONCLUSION: Renal lesion occurs in the
      diabetic Kunming mice induced by combination of high-fat diet and low-dose
      streptozotocin, and endoplasmic reticulum stress and CHOP may contribute to the
      injury process.

PMID- 27050785
TI  - The effect of amifostine on bacterial translocation after radiation induced acute
      enteritis.
AB  - PURPOSE: To investigate the effects of amifostine on bacterial translocation and
      overgrowth in colonic flora after acute radiation enteritis in a rat model.
      METHODS: Thirty-two female Wistar albino rats were divided into four groups:
      Group-1 (n=8): only normal saline was administered intraperitoneally. Group-2
      (n=8): first serum saline was administered intraperitoneally and 30 minutes later
      20 Gy radiation was applied to abdominopelvic region. Group-3 (n=8): only
      amifostine 200 ml/kg was administered intraperitoneally and radiation was not
      applied. Group-4 (n=8): first amifostine 200 ml/kg was administered
      intraperitoneally and 30 minutes later 20 Gy radiation was applied to
      abdominopelvic region. On the 5th day after radiation, samples of mesenteric
      lymph tissues and cecal contents were taken by laparotomy for microbiological
      culture. RESULTS: Intraperitoneal amifostine administration significantly
      decreased the bacterial overgrowth related to radiation in colon but did not
      significantly decrease the bacterial translocation. CONCLUSION: Although not
      providing a full protection on the damaged mucosal barrier, amifostine
      significantly decreased the bacterial overgrowth in the cecal content after high
      dose radiation. There is a need to find out appropriate amifostine dose under
      different radiation applications avoiding bacterial translocation in
      gastrointestinal system.

PMID- 27050786
TI  - Development of an ex vivo model of endovenous laser ablation of the great
      saphenous vein in a pilot study.
AB  - PURPOSE: To develop an ex vivo model for the analysis of macroscopic,
      histological and immunohistochemical changes after experimental endovenous laser
      ablation (EVLA) of the great saphenous vein (GSV). METHODS: We describe a model
      produced with glass tubes and introducer sheaths to mimic the physiological
      conditions of EVLA procedures, such as tumescence and blood flow. A pilot study
      was conducted to evaluate an ex vivo procedure of EVLA of an incompetent GSV
      segment using a 1470-nm radial fiber diode laser (7 W power) and an automatic
      pull-back device. The vein segment was analyzed macroscopically and by
      hematoxylin & eosin staining, elastic fiber histochemistry, Gomori's trichrome
      staining, and alpha-smooth muscle actin immunohistochemistry. RESULTS: No
      perforations were observed macroscopically. No muscle cell adhesion was observed
      in the central part of the ablated vein, showing tissue disruption. There was low
      labeling for elastic fibers, disruption of muscle fibers, and a reduced
      expression of the specific marker for this cell type. CONCLUSION: This ex vivo
      endovenous laser ablation model is a low cost alternative to in vivo experiments,
      providing standardized experimental conditions.

PMID- 27050788
TI  - Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by
      inhibiting HMGB1 expression in a rat model.
AB  - PURPOSE: To investigate the potential effects of pretreatment with allopurinol on
      renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats
      were subjected to right kidney uninephrectomy were randomly distributed into the
      following three groups (n=8): Group A (sham-operated group); Group B (ischemic
      group) with 30 min of renal ischemia after surgery; and Group C (allopurinol +
      ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h
      after renal reperfusion, the kidney was harvested to assess inflammation and
      apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal
      functional and histological grade scores following I/R injury (p<0.05). Compared
      with Group B, the expression levels of caspase-3 and Bax were markedly reduced in
      Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A
      newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed
      reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol
      had a protective effect on kidney ischemia/reperfusion injury, which might be
      related to the inhibition of HMGB1 expression.

PMID- 27050787
TI  - Can thiamine pyrophosphate prevent desflurane induced hepatotoxicity in rats?
AB  - PURPOSE: To investigate the effects of thiamine pyrophosphate (TPP) against
      desflurane induced hepatotoxicity. METHODS: Thirty experimental animals were
      divided into groups as healthy (HG), desflurane control (DCG) , TPP and
      desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After
      one hour of TPP administration, desflurane was applied for two hours. After 24
      hours, liver tissues of the animals killed with decapitation were removed. The
      oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The
      histopathological examinations were performed in the liver tissues for all rats.
      RESULTS: Notwithstanding the levels of oxidants and liver enzymes were
      significantly increased (p<0.0001), antioxidant levels were significantly
      decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were
      increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG
      (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation
      were observed in sinusoids and lymphocyte-rich inflammation results in the
      centrilobular and portal areas of liver tissue in DCG, these findings were
      observed less frequently in TDG. CONCLUSION : Thiamine pyrophosphate prevented
      liver oxidative damage induced with desflurane and may be useful in prophylaxis
      of desflurane induced hepatotoxicity.

PMID- 27050789
TI  - Grape seed protects cholestatic rats liver from ischemia/reperfusion injury.
AB  - PURPOSE: To determine the effect of grape-seed extract against
      ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino
      rats were divided into three groups. In control and study groups, cholestasis was
      provided by bile duct ligation. Seven days later, the rats were subjected to 30
      min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of
      50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and
      continued to the second operation in the study group. Serum, plasma and liver
      samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde,
      myeloperoxidase levels and histopathological examination were performed. RESULTS:
      Significant decrease in liver gluthation level and significant increase in
      malondialdehyde level and myeloperoxidase activity were observed after
      ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory
      analysis were also significantly higher in cholestatic I/R group. Hepatic
      necrosis and fibrosis were detected in histopathological examination. Oral grape
      seed extract administiration reversed all these parameters and histopathological
      findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract
      treatment can improve liver functions and attenuate the inflammation and
      oxidative stress in cholestatic ischemia/reperfusion injury.

PMID- 27050790
TI  - Borage oil attenuates progression of cardiac remodeling in rats after myocardial
      infarction.
AB  - PURPOSE: To investigate the effects of Borage oil on cardiac remodeling after
      myocardial infarction (MI). METHODS: Male Wistar rats underwent ligation of the
      left coronary artery and divided into three groups: MI (control), BO-18 (18 mg/kg
      of borage oil) and BO-180 (180 mg/kg of borage oil). After seven days, heart was
      arrested in diastole and processed for histological evaluation of: MI size, LV
      dilation, myocyte hypertrophy, inflammatory infiltration and fibrosis in MI
      region and in remote region. The relative weight of the lung was used as a marker
      of heart failure. The MI size was comparable among groups. RESULTS: Compared to
      control, BO treated groups showed lower weight of heart and lungs, reduced LV
      dilation and myocyte hypertrophy. Hemodynamic measurements were comparable. The
      treatment attenuated the inflammatory infiltration and fibrosis in remote
      myocardium. CONCLUSION: Borage oil attenuates progression of cardiac remodeling
      after myocardial infarction and congestive heart failure.

PMID- 27050791
TI  - Beneficial effects of beta-glucan against cisplatin side effects on the nervous
      system in rats 1.
AB  - PURPOSE: To investigate the protective effect of Bg on cisplatin (CP)-induced
      neurotoxicity in rats. METHODS: Twenty eight rats were randomly distributed into
      four groups. The first group was kept as a control. In the second group, CP was
      given at the single dose of 7 mg/kg intraperitoneally. In the third group, betag
      was orally administered at the dose of 50 mg/kg/day for 14 days. In the fourth
      group, CP and betag were given together at the same doses. RESULTS: CP treatment
      caused significant oxidative damage via induction of lipid peroxidation and
      reductions antioxidant defense system potency in the brain tissue. In addition,
      histopathological damage increased with CP treatment. On the other hand, betag
      treatment largely prevented oxidative and histopathological negative effects of
      CP. CONCLUSIONS: Cisplatin has severe neurotoxic effects in rats and betag
      supplementation has significant beneficial effects against CP toxicity depending
      on its antioxidant properties. Thus, it appears that betag might be useful
      against CP toxicity in patients with cancer in terms of nervous system.

PMID- 27050792
TI  - Genotyping of multidrug-resistant strains of Pseudomonas aeruginosa isolated from
      burn and wound infections by ERIC-PCR.
AB  - PURPOSE: To determine the genetic diversity of MDR P. aeruginosa strains isolated
      from burn and wound infections in Ahvaz, Iran, by ERIC-PCR. METHODS: From total
      99 strains of P. aeruginosa defined as MDR by using drug susceptibility testing,
      66 were subjected to ERIC-PCR analysis, comprises 53 strains isolated from burn
      infection, and 13 randomly selected strains from wound infection with higher
      resistance to combinations of more numbers of drugs. RESULTS: Eight clusters (I
      to VIII), and 50 single clones were generated for tested MDR isolates analyzed by
      ERIC-PCR. The high heterogeneity was observed among the isolates from burn
      infections including 16 isolates which were categorized in eight clusters and 37
      single clones. The isolates in clusters II, III, VI, VIII showed 100% similarity.
      CONCLUSIONS: The high level of genotypic heterogeneity in P. aeruginosa strains
      demonstrated no genetic correlation between them. Extremely high drug resistance
      in isolates from burn, suggests that efficient control measures and proper
      antibiotic policy should be observed.

PMID- 27050793
TI  - Translational microsurgery. A new platform for transplantation research.
AB  - PURPOSE: Clinical microsurgery has been introduced in many fields, while
      experimental microsurgery has the cross-disciplinary features of the sciences and
      techniques for growth of medicine, pharmacology, veterinary, engineering etc.
      Training protocol, proposing a new name as Translational Microsurgery, was
      introduced. METHODS: Reconstructive skills of hepatic artery in pediatric living
      donor liver transplantation were summarized. Ex vivo training protocol using
      artificial blood vessel for surgeons was proposed. RESULTS: Clinical microsurgery
      requires anastomosis with delicate arteries and limited field of view. Our
      training protocol revealed that the relation between the score and speed was
      seen, while not all the surgeons with enough experience got high score. This
      training led to muster clinical skills and to apply excellent experimental works.
      CONCLUSIONS: Our microsurgical training protocol has been planned from the points
      of clinical setting. Training for vascular anastomosis led to rodent
      transplantation models. These models were used for immunology and
      immunosuppressant research. Microsurgical techniques led to master catheter
      technique and to inject various drugs or gene vectors.

PMID- 27050794
TI  - Epidemiology of nontuberculous mycobacteria (NTM) amongst individuals with cystic
      fibrosis (CF).
AB  - BACKGROUND: Infection by nontuberculous mycobacteria (NTM) in patients with
      cystic fibrosis (CF) is often associated with significant morbidity. Limited,
      conflicting results are published regarding risk factors for pulmonary NTM
      disease. We analysed factors potentially associated with NTM in a large
      population of European patients with CF. METHODS: We investigated associations
      between presence of NTM and various factors for patients registered in the
      European Cystic Fibrosis Society Patient Registry. RESULTS: 374 (2.75%) of 13,593
      patients studied had at least one positive NTM culture within the study year. Age
      and FEV1-adjusted odds of NTM infection was more than 2.5 times higher (95%CI:
      1.79; 3.60) in patients infected by Stenotrophomonas maltophilia than in patients
      not infected (p<0.0001), 2.36 times higher (95%CI: 1.80;3.08) in patients with
      ABPA than without (p<0.0001), 1.79 times higher (95%CI: 1.34; 2.38) in patients
      who use bronchodilators than in patients who don't (p<0.0001), 1.49 times higher
      (95%CI: 1.18; 1.89) in patients who use inhaled antibiotics than in patients who
      don't (p=0.001), and 1.30 times higher (95%CI: 1.02; 1.66) in patients who use
      rhDNase than in patients who don't (p=0.032). CONCLUSIONS: NTM-positive cultures
      in individuals with CF are associated with distinct clinical variables. Improved
      data collection identifying risk factors for NTM infection will allow more
      focused screening strategies, and influence therapeutic choices and infection
      control measures in high-risk patients.

PMID- 27050796
TI  - Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in
      a real-life scenario: data from a prospective registry.
AB  - In randomized clinical trials, ticagrelor has been substituted in roughly one
      third of the patients during follow-up. To date, there are no studies addressing
      safety and modalities of switching from ticagrelor to clopidogrel. The aim of our
      study is to describe the occurrence, causes, and outcome of the switch from
      ticagrelor to clopidogrel in a real-life scenario. From June 2013 to March 2015,
      586 patients were treated with ticagrelor in our centre. Overall, 101 (17%)
      patients were switched to clopidogrel through a standardized protocol, and they
      were followed-up for 12 months. Ischemic and bleeding events were prospectively
      recorded. The switch from ticagrelor to clopidogrel occurred mostly after
      discharge (69 +/- 40 days), and the most frequent cause was the need of oral
      anticoagulation treatment, followed by bleeding events. Patients requiring
      ticagrelor discontinuation were older, more frequently female, with lower body
      mass index and creatinine clearance if compared to the "non-switched" group. In
      the 10 days after the switch, we did not observe ischemic adverse events. No
      definite/probable stent thrombosis was recorded. Before the switch, there was a
      significant higher occurrence of BARC bleedings in the "switched" group,
      particularly BARC 1 and 2. Our data confirm that the switch from ticagrelor to
      clopidogrel is common, and it occurs for several reasons. Our analysis did not
      demonstrate a significant increase in adverse cardiovascular events in the days
      following the switch from ticagrelor to clopidogrel, although larger studies are
      needed to validate our findings. 

PMID- 27050797
TI  - Development of Long-Circulating Zwitterionic Cross-Linked Micelles for Active
      Targeted Drug Delivery.
AB  - Blood stability, active targeting, and controlled drug release are the most
      important features to design desirable drug carriers. Here, we demonstrate a
      zwitterionic biodegradable cross-linked micelle based on a penta-block copolymer,
      which utilizes poly(carboxybetaine methacrylate) as hydrophilic segment,
      poly(epsilon-caprolactone) as biodegradable hydrophobic segment, poly(S-2
      hydroxyethyl-O-ethyl dithiocarbonate methacrylate) (PSODMA) block as thiol
      protecting segment for cross-linking, and cyclic Arg-Gly-Asp-d-Tyr-Lys [c(RGDyK)]
      as targeting ligand. As a result, this micelle possessed excellent colloidal
      stability at high dilution and in 50% fetal bovine serum. In vitro drug release
      experiment showed no burst release under physiological conditions but accelerated
      drug release in mimicking tumor tissue environment. In vivo tests showed that the
      drug-loaded micelles had prolonged half-life in bloodstream, enhanced therapeutic
      efficiency, and reduced cardiac toxicity and biotoxicity compared with free drug
      formulation. Taken together, the reported c(RGDyK)-modified zwitterionic
      interfacially cross-linked micelle has emerged as an appealing platform for
      cancer therapy.

PMID- 27050798
TI  - Cytotoxicity of goniodomin A and B in non contractile cells.
AB  - Goniodomin A is a phycotoxin produced by the dinoflagellates Alexandrium hiranoi
      (formerly Goniodoma pseudogoniaulax) and Alexandrium monilatum. This polyether
      macrolide exerts a potent antifungal effect and disturbs the actomyosin ATPase
      activity and the F-actin meshwork in diverse cell types. Goniodomin B is a fused
      acetal isomer isolated with goniodomin A with unknown activity. Histopathological
      changes induced by goniodomin A postulated hepatocytes as target cells. In this
      study both compounds induce a time and concentration dependent fall in the
      viability of Clone 9 rat hepatocytes. Furthermore, for both compounds, primary
      rat hepatocytes are almost 10 folds less sensitive than Clone 9 cells. Goniodomin
      A is highly effective in the nanomolar range while micromolar concentrations of
      goniodomin B are necessary to observe cytoxicity. Additionally, goniodomin A
      induced a significant increase in the F-actin and decrease in the G-actin content
      of Clone 9 cells but did not change the actin of primary cultured hepatocytes.
      However, goniodomin B could not exert significant alterations in the cytoskeleton
      of neither cell type. Futhermore goniodomin A as well as goniodomin B are
      cytotoxic to excitable cells. Both analogues triggered a time dependent decrease
      on viability in BE(2)-M17 human neuroblastoma cells. In this cell model
      goniodomin A increased the intracellular calcium and depolarized cells. We
      conclude that goniodomins A and B are biologically active molecules in
      hepatocytes and also in excitable cells BE(2)-M17. However, the analogue
      goniodomin B, whose activity is described in this work for the first time, is a
      much less potent compound. 

PMID- 27050799
TI  - Oxymatrine inhibits renal fibrosis of obstructive nephropathy by downregulating
      the TGF-beta1-Smad3 pathway.
AB  - This study investigated whether oxymatrine (OMT) treatment can ameliorate renal
      interstitial fibrosis in unilateral ureteral obstruction (UUO) mice model.
      Moreover, the potential mechanisms of such treatment were analyzed. Twenty-four
      C57/BL6 mice were randomly divided into three groups, namely sham group, vehicle
      plus unilateral ureteral obstruction (UUO)-treated group, and 100 mg/kg/d OMT
      plus UUO-treated group. All mice were euthanized seven days after surgery, and
      their kidneys were harvested. Renal injury, fibrosis, expression of
      proinflammatory cytokines, and the transforming growth factor-beta1/Smads (TGF
      beta/Smads) and nuclear factor-kappa B (NF-kappaB)-signaling pathways were
      assessed. The results showed OMT significantly prevented kidney injury and
      fibrosis, as evidenced by decreased expression of collagen-1 and fibronectin.
      Furthermore, OMT administration inhibited the release of inflammatory factors
      including tumor necrosis factor-alpha, (TNF-alpha) interleukin-1beta (IL-1beta),
      and interleukin-6 (IL-6), as well as phosphorylated NF-kappaB p65. In addition,
      OMT blocked the activation of myofibroblasts by inhibiting the TGF-beta/Smad3
      signaling pathway. The findings indicate that OMT-attenuated renal fibrosis and
      inflammation, and this renoprotective effect may be ascribed to the inactivation
      of the TGF-beta/Smad3 and NF-kappaB p65 pathways. 

PMID- 27050800
TI  - Nrf2 Activation Inhibits Effects of Thrombin in Human Amnion Cells and Thrombin
      Induced Preterm Birth in Mice.
AB  - CONTEXT: Nrf2 is a key transcription factor that modulates cell defense
      mechanisms against endogenous and exogenous stress. Previously, we reported that
      thrombin increased matrix metalloproteinases and prostaglandin synthesis in human
      amnion mesenchymal cells. OBJECTIVE: We sought to determine whether activation of
      Nrf2 alters the effect of thrombin on prostaglandin synthesis, protease
      activation, and cytokine release in human amnion. Furthermore, we analyzed the
      effect of Nrf2 activation on thrombin-induced preterm labor in mice. DESIGN:
      Primary human amnion mesenchymal cells and pregnant mice were employed to
      investigate the effect of Nrf2 on thrombin-induced inflammation and preterm
      birth. SETTING: This was a laboratory-based study using cells and mice. RESULTS:
      As expected, thrombin increased cyclooxygenase-2, IL-1beta, IL-6, IL-8, and
      matrix metalloproteinase-1 in amnion mesenchymal cells. Preincubation with Nrf2
      activators, diethyl maleate or 15-deoxy-Delta12, 14-prostaglandin J2 (15d-PGJ2),
      profoundly repressed thrombin-induced gene expression. In addition, Nrf2
      activation inhibited thrombin-induced cyclooxygenase-2 protein levels and
      secretion of prostaglandin E2, IL-1beta, IL-6, IL-8, TNFalpha, and granulocyte
      macrophage colony-stimulating factor in the media. Whereas vehicle and 15d-PGJ2
      did not alter gestational length, all pregnant mice treated with thrombin
      delivered preterm. 15d-PGJ2 delayed thrombin-induced preterm birth significantly.
      CONCLUSIONS: The results indicate that Nrf2 activation represents a key stress
      response in amnion mesenchyme cells and in pregnant mice to mitigate the adverse
      proinflammatory effects of thrombin on the fetal membranes. We suggest,
      therefore, that pharmacological activation of Nrf2 may prevent the increased risk
      of preterm premature rupture of the membranes associated with thrombin activation
      that accompanies subchorionic hemorrhage or bleeding during pregnancy.

PMID- 27050801
TI  - Impact of the Arg 16 allele of the B2AR gene on the effect of withdrawal of LABA
      in patients with moderate to severe asthma.
AB  - INTRODUCTION: Long-acting beta agonists (LABAs) are effective for controlling
      asthma, however questions about their safety have led to concerns over use.
      Genetic polymorphisms at the 16 amino acid position of the beta-2 adrenergic
      receptor gene (B2AR) may be associated with increased risk. METHODS: A
      randomized, double blind study was conducted in patients with moderate to severe
      asthma being treated with combined inhaled corticosteroids/LABA (ICS/LABA),
      comparing the effect of LABA continuation versus withdrawal on asthma outcomes
      among patients stratified by B2AR genotype (Arg/Arg vs. Gly/Gly at the 16th amino
      acid position). RESULTS: 67 participants (31 Arg/Arg, 36 Gly/Gly) were randomized
      to receive fluticasone alone (F) or continue combined fluticasone/salmeterol
      (F/S) after a run-in period on F/S. Among Gly/Gly subjects, those in the F/S
      treatment group showed improvement in AM PEFR (+ 8.4 L/s) whereas those receiving
      F alone experienced a reduction in AM PEFR over the study period (-14.4 L/s), (p
      = 0.06). There was no significant difference in morning peak expiratory flow rate
      (AM PEFR) in Arg/Arg participants randomized to receive F/S (-15.7L) vs F alone (
      5.6 L/s) (p = 0.61). There was no significant difference in exacerbations in the
      Arg/Arg subjects treated with F/S compared with those treated with F (p = 0.65).
      CONCLUSIONS: Withdrawal of LABA therapy in asthmatics with the Arg/Arg genotype
      at the 16th amino acid position of B2AR did not lead to significant improvement
      in AM PEFR. LABA withdrawal in the Gly/Gly genotype however led to a borderline
      significant decline in AM PEFR.

PMID- 27050802
TI  - Cardiac magnetic resonance imaging reveals frequent myocardial involvement and
      dysfunction in active rheumatoid arthritis.
AB  - OBJECTIVES: In rheumatoid arthritis (RA), cardiac involvement is common and often
      subclinical. We used cardiovascular magnetic resonance (CMR) to identify
      myocardial abnormalities in patients with active RA, free of clinical cardiac
      disease. METHODS: Sixty female patients with active RA aged <70 years and 21 sex-
      and age-matched control subjects underwent either 1.5T or 3T CMR imaging for
      analyses of T1 relaxation times, late gadolinium enhancement (LGE), and the
      volumes, and function of both ventricles. RESULTS: Determined using 1.5T CMR, the
      native left ventricular (LV) septal T1 time averaged 1011 (range 973-1046) ms in
      20 patients with RA vs. 976 (range 970-988) ms in 10 control subjects (p=0.045).
      With 3T CMR, the T1 time measured 1173 (range 1154-1187) ms in 29 RA patients vs.
      1053 (range 942-1148) ms in 9 control subjects (p=0.002). Myocardial LGE was
      detected in 55% of the RA patients. LV ejection fraction averaged 58 (range 56
      61)% vs. 66 (61-74)% (p<0.001) in the RA (n=60) and control groups (n=21),
      respectively, and corresponding means for LV peak filling rate were 2.99 (range
      2.32-3.33) s-1 vs. 3.39 (range 2.96-3.70) s-1 (p=0.012). The end-diastolic
      volumes of either ventricle were enlarged in RA compared to the control group
      (p<0.05 for both). CONCLUSIONS: In active RA, myocardial T1 relaxation times are
      prolonged suggesting diffuse inflammation or fibrosis. Local myocardial scars and
      inflammation, visible as LGE, are also common, as are impairments of LV systo
      diastolic function.

PMID- 27050803
TI  - Mandibular changes on panoramic imaging after head and neck radiotherapy.
AB  - OBJECTIVES: Changes to the radiographic appearance of the jaws after head and
      neck radiotherapy have not been thoroughly characterized. This retrospective
      study examines changes to the appearance of the mandible on panoramic images
      following intensity-modulated radiotherapy (IMRT) and relates these changes to
      medical co-morbidities and radiation dose. STUDY DESIGN: The medical and dental
      charts, and panoramic images of 126 patients who received IMRT at the Princess
      Margaret Hospital between January 1, 2005, and December 31, 2008, were analyzed
      independently by three observers. RESULTS: Of the 126 patients, 75 (60%) had post
      IMRT changes, as seen on panoramic images; most, 66 (88%), consisted of widened
      periodontal ligament space (WPLS). The median time to WPLS was 29 months after
      IMRT. Female gender and radiation dose correlated with decreased time to WPLS.
      CONCLUSIONS: These results indicate that WPLS is a common radiographic sequela
      after head and neck radiotherapy, underscoring its clinical significance as a
      reliable marker of irradiated bone. Furthermore, this type of WPLS needs to be
      differentiated from odontogenic inflammatory disease and cancer recurrence to
      avoid unnecessary treatment that may precipitate osteoradionecrosis.

PMID- 27050804
TI  - Clinicopathologic features associated with recurrence of the odontogenic
      keratocyst: a cohort retrospective analysis.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of clinical,
      radiographic, surgical and histopathologic parameters in the recurrence of
      disease in a series of odontogenic keratocysts (OKCs). STUDY DESIGN: The sample
      comprised 24 sporadic OKC lesions from 24 patients. All patients had no previous
      treatment history and were treated by the same surgeon using a uniform treatment
      protocol (enucleation with peripheral ostectomy preceded or not preceded by
      decompression). RESULTS: Fourteen lesions (58.4%) were first submitted to
      decompression procedure. Eight patients (33%) developed recurrent lesions, with a
      mean follow-up time of 60.5 months (standard deviation [SD] = 31.3) and a mean
      disease-free interval for recurrent lesions of 19 months (SD = 4.9). Recurrence
      was significantly associated with poor clinical response to decompression (P =
      .027), remaining tooth with radiographic evidence of insinuation of the lesion
      between the dental roots (P = .009), and the presence of budding of the basal
      cells layer together with epithelial islands in the fibrous capsule (P = .019).
      CONCLUSIONS: Clinical, radiographic and histopathologic parameters may affect the
      relapse rate of OKCs and should individually guide treatment choice.

PMID- 27050805
TI  - Nitrite Reduction to Nitrous Oxide and Ammonia by TiO2 Electrons in a Colloid
      Solution via Consecutive One-Electron Transfer Reactions.
AB  - The mechanism of nitrite reduction by excess electrons on TiO2 nanoparticles
      (eTiO2(-)) was studied under anaerobic conditions. TiO2 was loaded with up to 75
      electrons per particle, induced by gamma-irradiation of acidic TiO2 colloid
      solutions containing 2-propanol. Time-resolved kinetics and material analysis
      were performed, mostly at 1.66 g L(-1) TiO2. At relatively low nitrite
      concentrations (R = [eTiO2(-)]o/[nitrite]o > 1.5), eTiO2(-) decays via two
      consecutive processes; at higher concentrations, only one decay step is observed.
      The stoichiometric ratio Delta[eTiO2(-)]/[nitrite]o of the faster process is
      about 2. This process involves the one-electron reduction of nitrite, forming the
      nitrite radical (k1 = (2.0 +/- 0.2) * 10(6) M(-1) s(-1)), which further reacts
      with eTiO2(-) (k2) in competition with its dehydration to nitric oxide (NO) (k3).
      The ratios k2/k3 = (3.0 +/- 0.5) * 10(3) M(-1) and k2 > 1 * 10(6) M(-1) s(-1)
      were derived from kinetic simulations and product analysis. The major product of
      this process is NO. The slower stage of the kinetics involves the reduction of NO
      by eTiO2(-), and the detailed mechanism of this process has been discussed in our
      earlier publication. The results reported in this study suggest that several
      intermediates, including NO and NH2OH, are adsorbed on the titanium nanoparticles
      and give rise to inverse dependency of the respective reaction rates on the TiO2
      concentration. It is demonstrated that the reduction of nitrite by eTiO2(-)
      yields mainly N2O and NH3 via consecutive one-electron transfer reactions. 

PMID- 27050806
TI  - Modeling of in-use stability for tablets and powders in bottles.
AB  - A model is presented for determining the time when an active pharmaceutical
      ingredient in tablets/powders will remain within its specification limits during
      an in-use period; that is, when a heat-induction sealed bottle is opened for
      fixed time periods and where tablets are removed at fixed time points. This model
      combines the Accelerated Stability Assessment Program to determine the impact on
      degradation rates of relative humidity (RH) with calculations of the RH as a
      function of time for the dosage forms under in-use conditions. These
      calculations, in a conservative approach, assume that the air inside bottles with
      broached heat-induction seals completely exchanges with the external environment
      during periods when the bottle remains open. The solid dosages are assumed to
      sorb water at estimable rates during these openings. When bottles are capped, the
      moisture vapor transmission rate can be estimated to determine the changing RH
      inside the bottles between opening events. The impact of silica gel desiccants
      can also be included in the modeling. 

PMID- 27050807
TI  - Characterization of alanine to valine sequence variants in the Fc region of
      nivolumab biosimilar produced in Chinese hamster ovary cells.
AB  - Nivolumab is a therapeutic fully human IgG4 antibody to programmed death 1 (PD
      1). In this study, a nivolumab biosimilar, which was produced in our laboratory,
      was analyzed and characterized. Sequence variants that contain undesired amino
      acid sequences may cause concern during biosimilar bioprocess development. We
      found that low levels of sequence variants were detected in the heavy chain of
      the nivolumab biosimilar by ultra performance liquid chromatography (UPLC) and
      tandem mass spectrometry. It was further identified with UPLC-MS/MS by IdeS or
      trypsin digestion. The sequence variant was confirmed through addition of
      synthetic mutant peptide. Subsequently, the mixing base signal of normal and
      mutant sequence was detected through DNA sequencing. The relative levels of
      mutant A424V in the Fc region of the heavy chain have been detected and
      demonstrated to be 12.25% and 13.54%, via base peak intensity (BPI) and UV
      chromatography of the tryptic peptide mapping, respectively. A424V variant was
      also quantified by real-time PCR (RT-PCR) at the DNA and RNA level, which was
      19.2% and 16.8%, respectively. The relative content of the mutant was consistent
      at the DNA, RNA and protein level, indicating that the A424V mutation may have
      little influence at transcriptional or translational levels. These results
      demonstrate that orthogonal state-of-the-art techniques such as LC- UV- MS and RT
      PCR should be implemented to characterize recombinant proteins and cell lines for
      development of biosimilars. Our study suggests that it is important to establish
      an integrated and effective analytical method to monitor and characterize
      sequence variants during antibody drug development, especially for antibody
      biosimilar products.

PMID- 27050808
TI  - Aberrant expression of long noncoding RNA TMEVPG1 in patients with primary immune
      thrombocytopenia.
AB  - TMEVPG1 is a long noncoding RNA, which can promote Interferon gamma (IFNG)
      transcript as an enhancer. It has been reported that plasma IFNG concentration
      was elevated and partly due to dysregulation of micro RNAs in patients with
      primary immune thrombocytopenia (ITP). However, the effect of long noncoding RNA
      on IFNG expression in ITP is currently not well understood. To explore whether
      TMEVPG1 is involved in ITP, this study examined the TMEVPG1 expression and
      analyzed the association between TMEVPG1 transcript and IFNG expression in
      patients with ITP and healthy controls. The result showed that TMEVPG1 expression
      in peripheral blood mononuclear cells (PBMCs) from active ITP patients were lower
      than in that of healthy controls. Further activation for 24 h in vitro resulted
      in decreased TMEVPG1 while elevated IFNG mRNA and protein expressions in
      activated PBMCs compared with un-activated PBMCs both in ITP patients and healthy
      controls. However, TMEVPG1 and IFNG mRNA had same up-regulated tendency after
      short-time activation (1, 2 and 4 h) in healthy controls. In addition, we
      detected T helper 1 (Th1) cell associated transcription factors T-bet, STAT1 and
      STAT4 mRNA levels, and found T-bet mRNA expression was lower in PBMCs from ITP
      patient in remission compared with healthy controls. In conclusion, we speculated
      that TMEVPG1 could promote IFNG transcription, and IFNG over-expression negative
      feedback regulated on TMEVPG1 expression, which resulted in decreased TMEVPG1 in
      ITP patients.

PMID- 27050809
TI  - Group Maturity in a Community-Based Project.
AB  - Community-based projects have become popular as a method to address various
      community problems. Specifically important is that community members take an
      active role in these interventions resulting in sustainable social change.
      Although considerable literature exists on the dynamics of small group
      interaction, this article addresses how group processes differ in community-based
      projects. Instead of constructing a static model for group interaction, this
      discussion focuses on experiences from a recent community-based health project on
      the island of Grenada. Because community-based projects are directed by a diverse
      group of community members, maturity is described as a process of negotiation
      rather than consensus.

PMID- 27050810
TI  - The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix: A
      Review.
AB  - The placenta is a temporal, dynamic and diverse organ with important
      immunological features that facilitate embryonic and fetal development and
      survival, notwithstanding the fact that several aspects of its formation and
      function closely resemble tumor progression. Placentation in mammals is commonly
      used to characterize the evolution of species, including insights into human
      evolution. Although most placentas are discarded after birth, they are a high
      yield source for the isolation of stem/progenitor cells and are rich in
      extracellular matrix (ECM), representing an important resource for regenerative
      medicine purposes. Interactions among cells, ECM and bioactive molecules regulate
      tissue and organ generation and comprise the foundation of tissue engineering. In
      the present article, differences among several mammalian species regarding the
      placental types and classifications, phenotypes and potency of placenta-derived
      stem/progenitor cells, placental ECM components and current placental ECM
      applications were reviewed to highlight their potential clinical and biomedical
      relevance.

PMID- 27050811
TI  - Intraoperative inspection of the ureteropelvic junction during pyeloplasty is not
      sufficient to distinguish between extrinsic and intrinsic causes of obstruction:
      Correlation with histological analysis.
AB  - INTRODUCTION: Based on current knowledge, it is possible to have an initial
      diagnosis of intrinsic or extrinsic ureteropelvic junction obstruction (UPJO)
      based solely on clinical and imaging findings. However, it may not be possible to
      strictly discriminate an intrinsic case with an additional extrinsic component
      from a primarily intrinsic stenosis because of lower pole aberrant vessels. These
      two disorders may coexist or trigger each other. Herein, we aimed to compare the
      histological changes observed in intrinsic and extrinsic types of UPJO. Our
      hypothesis is that inspecting the UPJ during pyeloplasty may not be a sufficient
      way to delineate the underlying cause of obstruction in every individual.
      MATERIAL AND METHODS: We retrospectively reviewed the data of 56 patients who had
      dismembered pyeloplasty. The intrinsic and extrinsic groups consisted of 38 and
      18 patients, respectively. Masson's trichrome stain, CD117, and connexin 43
      (Cx43) antibody were used in histopathology and immunochemistry. Statistical
      calculations were done with chi-square and Mann-Whitney U tests. DISCUSSION:
      Connexin 43 staining pattern, CD117 positive cell count, and the extent of
      fibrosis did not differ significantly between extrinsic and intrinsic cases.
      However, the difference with regard to the degree of muscular hypertrophy was
      close to statistical significance. The exact pathophysiological mechanism
      underlying UPJO has yet to be elucidated. A study directly comparing both groups
      histologically is indeed rare. Our study showed that there are no significant
      differences between the intrinsic and extrinsic groups in terms of the pacemaker
      activity, gap junctional communication, and extent of fibrosis. Muscular
      hypertrophy, which was marginally higher in our extrinsic group, may persist
      despite successful relocation of the obstructing vessel. The main drawbacks of
      our study are; the absence of a control group and the retrospective study design
      with its inherent selection biases. CONCLUSIONS: Immunohistochemical profiles of
      intrinsic and extrinsic UPJOs resemble each other. Intraoperative inspection of
      the UPJ may not be enough for accurate discrimination for a surgical procedure
      that can correct only the extrinsic cause.

PMID- 27050812
TI  - Prolonged second stage in nulliparous with epidurals: a systematic review.
AB  - OBJECTIVE: Management of prolonged second stage of labor remains a clinical
      challenge. Nulliparous with epidurals are the most likely women to have a
      prolonged second stage and can be difficult to manage. The aim of this study was
      to evaluate the maternal and fetal morbidities associated with prolonged second
      stage of labor in nulliparous women with epidurals. METHODS: A systematic review
      of the literature was performed using PubMed, Ovid and Scopus searches for case
      series evaluating the morbidities of prolonged second stage of labor. Search
      terms used were "prolonged", "second stage", and "labor". Prolonged second stage
      was defined as three hours or more. Retrospective case series of prolonged second
      stage in nulliparous women with epidurals were identified. The primary outcome
      was the incidence of cesarean delivery. RESULTS: Two retrospective series with
      5350 nulliparous women with prolonged second stage were identified. 76.3% (4
      081/5 350) had an epidural. Of all nulliparous women with an epidural, 11.5% (4
      081/35 469) had prolonged second stage. Cesarean Delivery occurred in 19.8% of
      these cases (782/4 081), while 80.2% had a vaginal delivery. CONCLUSIONS: Over
      three quarters of nulliparous women with epidural diagnosed with a prolonged
      second stage deliver vaginally.

PMID- 27050813
TI  - A New Combined Technique Reducing the Risk of Paraplegia during Thoracoabdominal
      Aorta Replacement.
AB  - Acute spinal cord ischemia during thoracoabdominal aorta replacement is a
      dreadful complication. Existing tools (motor evoked potential [MEP] and
      somatosensory evoked potential [SSEP]) do not allow differentiating between
      central and peripheral paraplegia. Therefore, the surgeon often performs
      unnecessary reimplantation of intercostal arteries: this is time consuming, and
      significantly increases bleeding complications. We present a simple technique
      combining MEP and peripheral compound muscle action potential induced by
      posterior tibialis nerve stimulation, enabling the surgeon to quickly
      discriminate between central and peripheral neurologic injury. The surgeon has
      one more tool to drive in real time the optimal surgical strategy. This strategy
      guides the decision as to which side branches ought to be reimplanted, thus
      minimizing the risk of paraplegia.

PMID- 27050814
TI  - The Effect of Upper Airway Surgery on Continuous Positive Airway Pressure Levels
      and Adherence: A Systematic Review and Meta-Analysis.
AB  - Background /Aims: The aim of this study was to determine the effect of upper
      airway surgery (UAS) on continuous positive airway pressure (CPAP). A secondary
      objective was to determine if a decrease in CPAP from UAS increases CPAP
      adherence. METHODS: Studies were eligible for inclusion if a CPAP titration was
      performed both prior and following UAS in patients with obstructive sleep apnea
      (OSA). Studies that compared adherence to CPAP before and after UAS were included
      to evaluate the secondary objective. RESULTS: A total of 11 articles involving
      323 patients were included in the review. The results show that there was a mean
      reduction in CPAP of 1.40 cm H2O (95% CI -2.08 to -0.73). Four of the 11 papers,
      with a total of 80 patients, evaluated CPAP adherence and found a significant
      0.62-hour improvement on average (95% CI 0.22-1.01). CONCLUSION: Due to high
      levels of nonadherence, surgical intervention will play a role even in patients
      who are unlikely to be fully cured by surgery. UAS decreases the apnea-hypopnea
      index and modestly reduces CPAP while improving CPAP adherence in the majority of
      patients. The evidence suggests that UAS may have an adjunctive role in the
      management of OSA.

PMID- 27050815
TI  - Paucity of HPV-Related Head and Neck Cancers (HNC) in Nigeria.
AB  - INTRODUCTION: The burden of HPV-related Head and Neck Cancers (HNC) has been
      rising in the U.S. and other developed countries but this trend has not been
      reported in Africa. Objective of study was to evaluate the prevalence of HPV
      infection in HNC cancer cases seen between 1990 and 2011 at the tertiary health
      care institutions in Nigeria. METHODS: We retrieved 149 head and neck cancer
      formalin fixed, paraffin embedded tumor specimens diagnosed between 1990 and 2011
      from four teaching hospitals in Nigeria. One hundred and twenty-three blocks
      (83%) contained appropriate HNC for analysis while DNA extraction was successful
      in 60% (90/149). PCR amplification was successful in 33% (49/149) and Linear
      Array genotyping for HPV was successful in 11% (17/149) of these cases. These
      were in tumors from the larynx (6), cervical lymph nodes (3), nasal cavity (2),
      parotid (1), palate (1), maxillary sinus (1) and mandible (1). Two cases were non
      specific and none were from the oropharynx. Histologically, 41% (7/17) of the
      successfully genotyped blocks were squamous cell carcinomas (larynx 6, maxillary
      sinus 1). RESULTS AND CONCLUSION: We were unable to detect HPV in any of the HNC
      samples in our study. Our result may suggest that there is a low prevalence of
      HPV-related HNC among the adult population in Nigeria. Our results provide a
      benchmark to compare future incidence of HPV -related HNC in this community in
      future. We had significant analytical challenges from possible poor tissue
      processing and urge that future studies should prospectively collect samples and
      ensure high quality sample processing.

PMID- 27050816
TI  - Scent Lure Effect on Camera-Trap Based Leopard Density Estimates.
AB  - Density estimates for large carnivores derived from camera surveys often have
      wide confidence intervals due to low detection rates. Such estimates are of
      limited value to authorities, which require precise population estimates to
      inform conservation strategies. Using lures can potentially increase detection,
      improving the precision of estimates. However, by altering the spatio-temporal
      patterning of individuals across the camera array, lures may violate closure, a
      fundamental assumption of capture-recapture. Here, we test the effect of scent
      lures on the precision and veracity of density estimates derived from camera-trap
      surveys of a protected African leopard population. We undertook two surveys (a
      'control' and 'treatment' survey) on Phinda Game Reserve, South Africa. Survey
      design remained consistent except a scent lure was applied at camera-trap
      stations during the treatment survey. Lures did not affect the maximum movement
      distances (p = 0.96) or temporal activity of female (p = 0.12) or male leopards
      (p = 0.79), and the assumption of geographic closure was met for both surveys (p
      >0.05). The numbers of photographic captures were also similar for control and
      treatment surveys (p = 0.90). Accordingly, density estimates were comparable
      between surveys (although estimates derived using non-spatial methods (7.28-9.28
      leopards/100km2) were considerably higher than estimates from spatially-explicit
      methods (3.40-3.65 leopards/100km2). The precision of estimates from the control
      and treatment surveys, were also comparable and this applied to both non-spatial
      and spatial methods of estimation. Our findings suggest that at least in the
      context of leopard research in productive habitats, the use of lures is not
      warranted. 

PMID- 27050817
TI  - Antioxidant and Anti-Inflammatory Activities of Unexplored Brazilian Native
      Fruits.
AB  - Brazilian native fruits are unmatched in their variety, but a poorly explored
      resource for the development of food and pharmaceutical products. The aim of this
      study was to evaluate the phenolic composition as well as the antioxidant and
      anti-inflammatory activities of the extracts of leaves, seeds, and pulp of four
      Brazilian native fruits (Eugenia leitonii, Eugenia involucrata, Eugenia
      brasiliensis, and Eugenia myrcianthes). GC-MS analyses of the ethanolic extracts
      showed the presence of epicatechin and gallic acid as the major compounds in
      these fruits. Antioxidant activity was measured using synthetic DPPH free-radical
      scavenging, beta-carotene bleaching assay, and reactive oxygen species (ROO., O2.
      , and HOCl). The fruit extracts also exhibited antioxidant effect against
      biologically relevant radicals such as peroxyl, superoxide, and hypochlorous
      acid. In general, the pulps were the fruit fractions that exhibited the lowest
      antioxidant activities, whereas the leaves showed the highest ones. The anti
      inflammatory activity was assessed in an in vivo model using the carrageenan
      induced neutrophil migration assay, which evaluates the inflammatory response in
      the acute phase. The pulp, seeds, and leaves of these fruits reduced the
      neutrophil influx by 40% to 64%. Based on these results, we suggest that the anti
      inflammatory activity of these native fruits is related to the modulation of
      neutrophil migration, through the inhibition of cytokines, chemokines, and
      adhesion molecules, as well as to the antioxidant action of their ethanolic
      extracts in scavenging the free-radicals released by neutrophils. Therefore,
      these native fruits can be useful to produce food additives and functional foods.

PMID- 27050818
TI  - Enhancing Connectedness Through Peer Training for Community-Dwelling Older
      People: A Person Centred Approach.
AB  - Social interaction and connectedness is important to the mental health and
      wellbeing of older people. The aim of this research study was to facilitate and
      increase opportunities for social connectedness for older people living in
      regional areas through the use of technology training. Weekly technology training
      sessions were conducted at a Seniors Citizen's Club with a peer trainer (an
      experienced, retired computer teacher) and sessions were attended not only by the
      six study participants, but also by other club members, with up to 15 club
      members participating in sessions. Data analysis involved all documents generated
      by the project, including the individual interviews, researcher observations of
      training sessions, reports from the peer trainer and weekly diaries maintained by
      participants. Findings demonstrated that computer training at the Senior Citizens
      Club helped participants build group cohesion and to form tiered connections with
      partners, family, and friends with whom they no longer live. When the trainer is
      seen as a peer, and training is person-centred, older people are more receptive
      to learning, exploring, and experimenting with technology. Although only six
      people were involved in the in-depth evaluation part of the study, voluntary
      training with the trainer in the absence of any funding continues even to this
      present time. The outcome of this research reinforces the potential for
      technology facilitated tiered connectivity to enhance the quality of life for
      older people living in regional and rural Australia. 

PMID- 27050819
TI  - Disparity and Trends in Secondhand Smoke Exposure among Japanese Employees,
      Particularly Smokers vs. Non-Smokers.
AB  - BACKGROUND: Monitoring disparities in secondhand smoke (SHS) exposure is
      important for tailoring smoke-free policies to the needs of different groups. We
      examined disparity and trends in SHS exposure among both nonsmokers and smokers
      at Japanese workplaces between 2002 and 2012. METHODS: A total of 32,940
      employees in nationally representative, population-based, repeated cross
      sectional surveys in 2002, 2007 and 2012 in Japan was analyzed. Adjusted rate
      ratios for workplace SHS exposure from other people ("everyday" and "everyday or
      sometimes") were calculated according to covariates, using log-binomial
      regression models with survey weights. In this survey, employees who do not smoke
      at workplace are defined as workplace-nonsmokers; and those smoke at workplace
      are used as workplace-smokers. SHS exposure for smokers does not involve their
      own SHS. RESULTS: While everyday SHS exposure prevalence in workplace-nonsmokers
      decreased markedly (33.2% to 11.4%), that in workplace-smokers decreased only
      slightly (63.3% to 55.6%). Workplace-smokers were significantly more likely to
      report everyday SHS exposure than workplace-nonsmokers, and the degree of
      association increased over time: compared with the nonsmokers (reference),
      covariates-adjusted rate ratio (95% confidence interval) for the smokers
      increased from 1.70 (1.62-1.77) in 2002 to 4.16 (3.79-4.56) in 2012. Similar
      results were observed for everyday or sometimes SHS exposure. Compared with
      complete workplace smoking bans, partial and no bans were consistently and
      significantly associated with high SHS exposure among both nonsmokers and
      smokers. We also observed disparities in SHS exposure by employee
      characteristics, such as age group and worksite scale. CONCLUSIONS: Although
      overall SHS exposure decreased among Japanese employees between 2002 and 2012,
      the SHS exposure disparity between nonsmokers and smokers widened. Because
      smokers reported more frequent SHS exposure than nonsmokers, subsequent mortality
      due to SHS exposure may be higher in smokers than in nonsmokers. This information
      may be useful for advocating workplace smoke-free policies.

PMID- 27050820
TI  - Linking inflammation and mechanotransduction in stem cell regulation.

PMID- 27050821
TI  - Eyes in a funeral wake from the National Archaeological Museum (Madrid).

PMID- 27050822
TI  - Associations between the FAS -670 A/G, -1377 G/A, and FASL -844 T/C polymorphisms
      and susceptibility to systemic lupus erythematosus: a meta-analysis.
AB  - OBJECTIVES: The aim of this study was to determine whether the FAS, and FASL
      polymorphisms are associated with susceptibility to systemic lupus erythematosus
      (SLE). METHODS: A meta-analysis was conducted on the associations between the FAS
      -670 A/G, FAS -1377 G/A, and FASL -844 T/C polymorphisms and SLE. RESULTS: A
      total of eleven articles met the study inclusion criteria. Meta-analysis
      indicated an association between SLE and the FAS -670 A/G polymorphism in the
      dominant model (OR=0.629, 95% CI=0.409-0.967, p=0.035). Stratification by
      ethnicity indicated an association between the FAS -670 GG+GA genotype and SLE in
      Asian populations (OR=0.464, 95% CI=0.218-0.988, p=0.046). Meta-analysis
      indicated an association between SLE and the FAS -1377 AA+AG genotype (OR=0.712,
      95% CI=0.528 - 0.961, p=0.027), and an association between SLE and the FASL +844
      C allele was found (OR=1.377, 95% CI=1.162 - 1.633, p=2.3x10(-4)). Meta-analyses
      using the recessive model or homozygote contrast showed the same pattern as the
      meta-analysis of the FASL +844 C allele, that is, a significant association with
      SLE. CONCLUSIONS: This meta-analysis demonstrates that the FAS -670 A/G, FAS 
      1377 G/A, and FASL -844 T/C polymorphisms are associated with susceptibility to
      SLE.

PMID- 27050823
TI  - Measuring Post-Partum Haemorrhage in Low-Resource Settings: The Diagnostic
      Validity of Weighed Blood Loss versus Quantitative Changes in Hemoglobin.
AB  - BACKGROUND: Accurate estimation of blood loss is central to prompt diagnosis and
      management of post-partum hemorrhage (PPH), which remains a leading cause of
      maternal mortality in low-resource countries. In such settings, blood loss is
      often estimated visually and subjectively by attending health workers, due to
      inconsistent availability of laboratory infrastructure. We evaluated the
      diagnostic accuracy of weighed blood loss (WBL) versus changes in peri-partum
      hemoglobin to detect PPH. METHODS: Data from this analysis were collected as part
      of a randomized controlled trial comparing oxytocin with misoprostol for PPH
      (NCT01866241). Blood samples for complete blood count were drawn on admission and
      again prior to hospital discharge or before blood transfusion. During delivery,
      women were placed on drapes and had pre-weighed sanitary towels placed around
      their perineum. Blood was then drained into a calibrated container and the
      sanitary towels were added to estimate WBL, where each gram of blood was
      estimated as a milliliter. Sensitivity, specificity, negative and positive
      predictive values (PPVs) were calculated at various blood volume loss and time
      combinations, and we fit receiver-operator curves using blood loss at 1, 2, and
      24 hours compared to a reference standard of haemoglobin decrease of >10%.
      RESULTS: A total of 1,140 women were enrolled in the study, of whom 258 (22.6%)
      developed PPH, defined as a haemoglobin drop >10%, and 262 (23.0%) had WBL
      >=500mL. WBL generally had a poor sensitivity for detection of PPH (<75% for most
      volume-time combinations). In contrast, the specificity of WBL was high with
      blood loss >= 500mL at 1h and >=750mL at any time points excluding PPH in over
      97% of women. As such, WBL has a high PPV (>85%) in high prevalence settings when
      WBL exceeds 750mL. CONCLUSION: WBL has poor sensitivity but high specificity
      compared to laboratory-based methods of PPH diagnosis. These characteristics
      correspond to a high PPV in areas with high PPH prevalence. Although WBL is not
      useful for excluding PPH, this low-cost, simple and reproducible method is
      promising as a reasonable method to identify significant PPH in such settings
      where quantifiable red cell indices are unavailable.

PMID- 27050824
TI  - The child's perspective as a guiding principle: Young children as co-designers in
      the design of an interactive application meant to facilitate participation in
      healthcare situations.
AB  - During the last decade, interactive technology has entered mainstream society.
      Its many users also include children, even the youngest ones, who use the
      technology in different situations for both fun and learning. When designing
      technology for children, it is crucial to involve children in the process in
      order to arrive at an age-appropriate end product. In this study we describe the
      specific iterative process by which an interactive application was developed.
      This application is intended to facilitate young children's, three-to five years
      old, participation in healthcare situations. We also describe the specific
      contributions of the children, who tested the prototypes in a preschool, a
      primary health care clinic and an outpatient unit at a hospital, during the
      development process. The iterative phases enabled the children to be involved at
      different stages of the process and to evaluate modifications and improvements
      made after each prior iteration. The children contributed their own perspectives
      (the child's perspective) on the usability, content and graphic design of the
      application, substantially improving the software and resulting in an age
      appropriate product.

PMID- 27050825
TI  - Long-term audiologic follow-up of carboplatin-treated children with
      retinoblastoma.
AB  - BACKGROUND: Children treated for retinoblastoma with carboplatin have an
      increased risk for ototoxicity. Impaired hearing may have major consequences for
      these children, because they often suffer from reduced vision. Previous studies
      have shown limited information on the incidence and severity of carboplatin
      induced ototoxicity and the used audiologic methods. The frequency of
      audiological testing is often limited and the audiologic follow-up time is
      relatively short. OBJECTIVE: The aim of this study was to determine the long-term
      effects of carboplatin ototoxicity in children with retinoblastoma. MATERIALS AND
      METHODS: In this retrospective non-randomized single center cohort study, we
      reviewed audiologic results of 25 patients. Experienced audiologists analyzed the
      pure-tone audiograms. RESULTS: All patients had normal hearing prior to therapy
      and had a mean age of 11 months at first carboplatin administration. The mean
      audiologic follow-up was 12.0 years with a median of 11.6 (IQR 4.8) years. Three
      patients were excluded: two passed away and one could not participate in the
      audiologic tests. One of the 22 included patients developed sustained low-grade
      bilateral high-frequency hearing loss between 2 and 7 years after the last
      carboplatin dose. In one patient it was not possible to make a reliable
      conclusion due to a conductive hearing loss component. Twenty patients had normal
      hearing. CONCLUSIONS: We observed no clear effect between carboplatin
      administration in young children and clinical significant ototoxicity in the long
      term. One child showed low-grade bilateral high-frequency hearing loss.

PMID- 27050826
TI  - Development of a Brief Form of the Interpersonal Reactivity Index (B-IRI).
AB  - The Interpersonal Reactivity Index (IRI) is a standardized self-report measure of
      disposition to empathic responsiveness for the general adult population (the
      domain for which it was developed), and for the general adolescent population.
      The IRI has a number of problems, however, including some uncertainty about its
      factor structure, low reliabilities, and poor readability of some items for
      people with limited literacy skills. To address these issues, we constructed an
      abbreviated form of the index, the Brief IRI (B-IRI). Three studies demonstrated
      that this 16-item B-IRI has a clear and coherent factor structure, adequate
      internal consistency, measurement invariance across gender and age, and
      theoretically meaningful associations with a range of external criteria that
      support its construct validity. The B-IRI substantially preserves the
      psychometric properties of the long form, and we recommend its use in all
      research settings.

PMID- 27050827
TI  - Microbial Ecology and Evolution in the Acid Mine Drainage Model System.
AB  - Acid mine drainage (AMD) is a unique ecological niche for acid- and toxic-metals
      adapted microorganisms. These low-complexity systems offer a special opportunity
      for the ecological and evolutionary analyses of natural microbial assemblages.
      The last decade has witnessed an unprecedented interest in the study of AMD
      communities using 16S rRNA high-throughput sequencing and community genomic and
      postgenomic methodologies, significantly advancing our understanding of microbial
      diversity, community function, and evolution in acidic environments. This review
      describes new data on AMD microbial ecology and evolution, especially dynamics of
      microbial diversity, community functions, and population genomes, and further
      identifies gaps in our current knowledge that future research, with integrated
      applications of meta-omics technologies, will fill.

PMID- 27050828
TI  - Surface energetics and protein-protein interactions: analysis and mechanistic
      implications.
AB  - Understanding protein-protein interactions (PPI) at the molecular level is a
      fundamental task in the design of new drugs, the prediction of protein function
      and the clarification of the mechanisms of (dis)regulation of biochemical
      pathways. In this study, we use a novel computational approach to investigate the
      energetics of aminoacid networks located on the surface of proteins, isolated and
      in complex with their respective partners. Interestingly, the analysis of
      individual proteins identifies patches of surface residues that, when mapped on
      the structure of their respective complexes, reveal regions of residue-pair
      couplings that extend across the binding interfaces, forming continuous motifs.
      An enhanced effect is visible across the proteins of the dataset forming larger
      quaternary assemblies. The method indicates the presence of energetic signatures
      in the isolated proteins that are retained in the bound form, which we
      hypothesize to determine binding orientation upon complex formation. We propose
      our method, BLUEPRINT, as a complement to different approaches ranging from the
      ab-initio characterization of PPIs, to protein-protein docking algorithms, for
      the physico-chemical and functional investigation of protein-protein
      interactions. 

PMID- 27050829
TI  - Double Switching of Two Rings in Palindromic [3]Pseudorotaxanes: Cooperativity
      and Mechanism of Motion.
AB  - The existence of two rings in [3]pseudorotaxanes presents opportunities for those
      rings to undergo double switching and cooperative mechanical coupling. To
      investigate this capability, we identified a new strategy for bringing two rings
      into contact with each other and conducted mechanistic studies to reveal their
      kinetic cooperativity. A redox-active tetrazine ligand bearing two binding sites
      was selected to allow for two mobile copper(I) macrocycle ring moieties to come
      together. To realize this switching modality, ligands were screened against their
      ability to serve as stations on which the rings are initially parked, ultimately
      identifying 5,5'-dimethyl-2,2'-bipyridine. The kinetics of switching a macrocycle
      in a single-site [2]pseudorotaxane between bipyridine and single-site tetrazine
      stations were examined using electrochemistry. The forward movement was rate
      limited by the bimolecular reaction between reduced tetrazine and bipyridine
      [2]pseudorotaxane. Two bipyridines were then used with a double-site tetrazine to
      verify double switching of two rings. Our results indicated stepwise movements,
      with the first ring moving 4 times more frequently (faster) than the second.
      While this behavior is indicative of anticooperative kinetics, positive
      thermodynamic cooperativity sets the two rings in motion even though just one
      tetrazine is reduced with one electron. Double switching in this
      [3]pseudorotaxane uniquely demonstrates how a series of independent thermodynamic
      states and kinetic paths govern an apparently simple mechanical motion. 

PMID- 27050830
TI  - Abuse-deterrent formulations of prescription opioid analgesics in the management
      of chronic noncancer pain.
AB  - Misuse, abuse and diversion of prescription opioid analgesics represent a global
      public health concern. The development of abuse-deterrent formulations (ADFs) of
      prescription opioid analgesics is an important step toward reducing abuse and
      diversion of these medications, as well as potentially limiting medical
      consequences when misused or administered in error. ADFs aim to hinder extraction
      of the active ingredient, prevent administration through alternative routes
      and/or make abuse of the manipulated product less attractive, less rewarding or
      aversive. However, opioid ADFs may still be abused via the intended route of
      administration by increasing the dose and/or dosing frequency. The science of
      abuse deterrence and the regulatory landscape are still relatively new and
      evolving. This paper reviews the current status of opioid ADFs, with particular
      focus on different approaches that can be used to deter abuse, regulatory
      considerations and implications for clinical management. 

PMID- 27050831
TI  - RNA metabolism: Co-transcriptional splicing at nucleotide resolution.

PMID- 27050832
TI  - Production and characterization of monoclonal antibodies against alpha-globin
      chain-containing human hemoglobins for detecting alpha-thalassemia disease.
AB  - Monoclonal antibodies against alpha-globin containing human Hbs, named AMS-Alpha1
      and AMS-Alpha 2, were produced by the hybridoma technique using spleen cells
      enriched by the newly developed B lymphocyte enrichment protocol. These two
      monoclonal antibodies were of IgM class, reacting to only intact form of human
      Hbs A, A2, E, and F, which contain alpha-globin chain. By the indirect ELISA, the
      AMS-Alpha1 and AMS-Alpha 2 quantified less amount of alpha-globin chain
      containing hemoglobins in HbH disease than the SEA-alpha thalassemia 1 carriers
      and normal individuals. It was thus anticipated that these monoclonal antibodies
      can be used for detecting Hb Bart's hydrops fetalis in which no alpha-globin
      chain is produced. 

PMID- 27050833
TI  - A Serpiginous Plaque on the Trunk.

PMID- 27050834
TI  - More Than Meets the Eye: Split-Second Social Perception.
AB  - Recent research suggests that visual perception of social categories is shaped
      not only by facial features but also by higher-order social cognitive processes
      (e.g., stereotypes, attitudes, goals). Building on neural computational models of
      social perception, we outline a perspective of how multiple bottom-up visual cues
      are flexibly integrated with a range of top-down processes to form perceptions,
      and we identify a set of key brain regions involved. During this integration,
      'hidden' social category activations are often triggered which temporarily impact
      perception without manifesting in explicit perceptual judgments. Importantly,
      these hidden impacts and other aspects of the perceptual process predict
      downstream social consequences - from politicians' electoral success to several
      evaluative biases - independently of the outcomes of that process.

PMID- 27050835
TI  - Older women's responses and decisions after a fall: The work of getting "back to
      normal".
AB  - In this descriptive qualitative research, we examined older women's responses and
      decisions after experiencing a fall. Falls were unexpected, sudden events that
      heightened these women's awareness of their physical, emotional, spiritual, and
      social independence. Interviewees reported assessing personal, physical, and
      emotional needs; feeling burdened by the extra work; trying to get back to
      normal; seeking and obtaining assistance and spiritual support; avoiding specific
      people, objects, and places; planning ahead; and putting the fall out of mind.
      Consideration of older women's post-fall responses and decisions should be
      incorporated into fall prevention and management programs, services, and clinical
      recommendations.

PMID- 27050836
TI  - Association of Patient Care with Ventilator-Associated Conditions in Critically
      Ill Patients: Risk Factor Analysis.
AB  - BACKGROUND: Ventilator-associated conditions (VACs), for which new surveillance
      definitions and methods were issued by the Center for Disease Control and
      Prevention (CDC), are respiratory complications occurring in conjunction with the
      use of invasive mechanical ventilation and are related to adverse outcomes in
      critically ill patients. However, to date, risk factors for VACs have not been
      adequately established, leading to a need for developing a better understanding
      of the risks. The objective of this study was to explore care-related risk
      factors as a process indicator and provide valuable information pertaining to VAC
      preventive measures. METHODS: This retrospective, single-center, cohort study was
      conducted in the intensive-care unit (ICU) of a university hospital in Japan.
      Patient data were automatically sampled using a computerized medical records
      system and retrospectively analyzed. Management and care-related, but not host
      related, factors were exhaustively analyzed using multivariate analysis for risks
      of VACs. VAC correlation to mortality was also investigated. RESULTS: Of the 3122
      patients admitted in the ICU, 303 ventilated patients meeting CDC-specified
      eligibility criteria were included in the analysis. Thirty-seven VACs (12.2%)
      were found with a corresponding rate of 12.1 per 1000 ventilator days.
      Multivariate analysis revealed four variables related to patient care as risk
      factors for VACs: absence of intensivist participation in management of
      ventilated patients [adjusted HR (AHR): 7.325, P < 0.001)], using relatively
      higher driving pressure (AHR: 1.216, P < 0.001), development of edema (AHR:
      2.145, P = 0.037), and a larger body weight increase (AHR: 0.058, P = 0.005).
      Furthermore, this research confirmed mortality differences in patients with VACs
      and statistically derived risks compared with those without VACs (HR: 2.623, P =
      0.008). CONCLUSION: Four risk factors related to patient care were clearly
      identified to be the key factors for VAC preventive measures.

PMID- 27050837
TI  - Soil Iron Content as a Predictor of Carbon and Nutrient Mobilization in Rewetted
      Fens.
AB  - Rewetted, previously drained fens often remain sources rather than sinks for
      carbon and nutrients. To date, it is poorly understood which soil characteristics
      stimulate carbon and nutrient mobilization upon rewetting. Here, we assess the
      hypothesis that a large pool of iron in the soil negatively affects fen
      restoration success, as flooding-induced iron reduction (Fe3+ to Fe2+) causes a
      disproportionate breakdown of organic matter that is coupled with a release of
      inorganic compounds. We collected intact soil cores in two iron-poor and two iron
      rich drained fens, half of which were subjected to a rewetting treatment while
      the other half was kept drained. Prolonged drainage led to the mobilization of
      nitrate (NO3-, > 1 mmol L-1) in all cores, regardless of soil iron content. In
      the rewetted iron-rich cores, a sharp increase in pore water iron (Fe)
      concentrations correlated with concentrations of inorganic carbon (TIC, > 13 mmol
      L-1) and dissolved organic carbon (DOC, > 16 mmol L-1). Additionally, ammonium
      (NH4+) accumulated up to phytotoxic concentrations of 1 mmol L-1 in the pore
      water of the rewetted iron-rich cores. Disproportionate mobilization of Fe, TIC,
      DOC and NH4+ was absent in the rewetted iron-poor cores, indicating a strong
      interaction between waterlogging and iron-mediated breakdown of organic matter.
      Concentrations of dissolved phosphorus (P) rose slightly in all cores upon
      rewetting, but remained low throughout the experiment. Our results suggest that
      large pools of iron in the top soil of drained fens can hamper the restoration of
      the fen's sink-service for ammonium and carbon upon rewetting. We argue that
      negative effects of iron should be most apparent in fens with fluctuating water
      levels, as temporary oxygenation allows frequent regeneration of Fe3+. We
      conclude that rewetting of iron-poor fens may be more feasible for restoration. 

PMID- 27050838
TI  - Peroxisome proliferator-activated receptors (PPAR) downregulate the expression of
      pro-inflammatory molecules in an experimental model of myocardial infarction.
AB  - Myocardial infarction (MI) has been associated with an inflammatory response and
      a rise in TNF-alpha, interleukin (IL)-1beta, and IL-6. Peroxisome proliferator
      activated receptors (PPARs) promote a decreased expression of inflammatory
      molecules. We aimed to study whether PPAR stimulation by clofibrate decreases
      inflammation and reduces infarct size in rats with MI. Male Wistar rats were
      randomized into 3 groups: control, MI + vehicle, and MI + clofibrate (100 mg/kg).
      Treatment was administered for 3 consecutive days, previous to 2 h of MI. MI
      induced an increase in protein expression, mRNA content, and enzymatic activity
      of inducible nitric oxide synthase (iNOS). Additionally, MI incited an increased
      expression of matrix metalloproteinase (MMP)-2 and MMP-9, intercellular adhesion
      molecule (ICAM)-1, and IL-6. MI also elevated the nuclear content of nuclear
      factor-kappaB (NF-kappaB) and decreased IkappaB, both in myocyte nuclei and
      cytosol. Clofibrate treatment prevented MI-induced changes in iNOS, MMP-2 and MMP
      9, ICAM-1, IL-6, NF-kappaB, and IkappaB. Infarct size was smaller in clofibrate
      treated rats compared to MI-vehicle animals. In silico analysis exhibited 3
      motifs shared by genes from renin-angiotensin system, PPARalpha, iNOS, MMP-2 and
      MMP-9, ICAM-1, and VCAM-1, suggesting a cross regulation. In conclusion,
      PPARalpha-stimulation prevents overexpression of pro-inflammatory molecules and
      preserves viability in an experimental model of acute MI. 

PMID- 27050839
TI  - Target Specific Tactics in Olefin Metathesis: Synthetic Approach to cis-syn-cis
      Triquinanes and -Propellanes.
AB  - A concise and simple synthetic approach to cis-syn-cis-triquinanes and 
      propellanes has been demonstrated via olefin metathesis starting with exo-nadic
      anhydride. This approach involves a ring-opening and ring-closing metathesis
      sequence of norbornene derivatives using Grubb's catalyst. Early-stage
      diallylation of norbornene derivatives is demonstrated followed by ring-closing
      metathesis that delivers propellanes exclusively. Surprisingly, ring-opening
      metathesis, late-stage diallylation, followed by ring-closing metathesis delivers
      triquinane as well as propellane derivatives. 

PMID- 27050840
TI  - MAPx (Mobility Aid Personalization): examining why older adults "pimp their ride"
      and the impact of doing so.
AB  - We all do this. We personalize things. We buy leopard-printed seat covers and
      fuzzy dice for our cars, and display action figures and photographs in our
      offices. Studying older adults who have extended this process of personalization
      to their mobility devices, the purpose of the mobility aid personalization (MAPx)
      project is to examine MAPx and its impact on the health and mobility of older
      adults. Using a qualitative research design, field observations and interviews
      were conducted with 72 older adults to gain an in-depth understanding of device
      customization from an emic (insider's) perspective. Findings illustrate that
      older adults personalize their devices for reasons of fun, function and fashion.
      MAPx - the process of purposefully selecting or modifying a mobility device to
      suit individual needs and preferences - was also found to promote health and
      mobility by encouraging device acceptance, increasing social participation,
      enhancing joy and preserving identity. MAPx makes an important contribution to
      our understanding of the complex relationship between older adults and assistive
      devices and provides a new approach to some old problems including falls,
      inactivity and social isolation. Encouraging MAPx is a promising rehabilitation
      strategy for promoting health and community mobility among the older adult
      population. Implications for Rehabilitation Personalizing an assistive device
      facilitates device acceptance, promotes health and well-beingand should be
      supported and encouraged in rehabilitative care. Choice, variety and access are
      critical aspects of assistive devices; vendors, manufacturers andpractitioners
      should work together to provide clients with a greater range of affordable
      optionsfor new devices. Function is more than mechanical or physical; social
      factors including social identity, stigma andsocial roles must be adequately
      considered and explicit in rehabilitative practice.

PMID- 27050841
TI  - Remarkable influence of slack on the vibration of a single-walled carbon nanotube
      resonator.
AB  - We for the first time quantitatively investigate experimentally the remarkable
      influence of slack on the vibration of a single-walled carbon nanotube (SWCNT)
      resonator with a changeable channel length fabricated in situ inside a scanning
      electron microscope, compare the experimental results with the theoretical
      predictions calculated from the measured geometric and mechanical parameters of
      the same SWCNT, and find the following novel points. We demonstrate
      experimentally that as the slack s is increased from about zero to 1.8%, the
      detected vibration transforms from single-mode to multimode vibration, and the
      gate-tuning ability gradually attenuates for all the vibration modes. The
      quadratic tuning coefficient alpha decreases linearly with 1/?s when the gate
      voltage V(g)dc is small and the nanotube resonator operates in the beam regime.
      The linear tuning coefficient gamma decreases linearly with 1/ (4?S) when V(g)dc
      has an intermediate value and the nanotube resonator operates in the catenary
      regime. The calculated alpha and gamma fit the experimental values of the even in
      plane mode reasonably well. As the slack is increased, the quality factor Q of
      the resonator linearly goes up, but the increase is far less steep than that
      predicted by the previous theoretical study. Our results are important to
      understand and design resonators based on CNT and other nanomaterials.

PMID- 27050842
TI  - Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by
      Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker.
AB  - Neuronal nitric oxide synthase (nNOS) is an important therapeutic target for the
      treatment of various neurodegenerative disorders. A major challenge in the design
      of nNOS inhibitors focuses on potency in humans and selectivity over other NOS
      isoforms. Here we report potent and selective human nNOS inhibitors based on the
      2-aminopyridine scaffold with a central pyridine linker. Compound 14j, the most
      promising inhibitor in this study, exhibits excellent potency for rat nNOS (Ki =
      16 nM) with 828-fold n/e and 118-fold n/i selectivity with a Ki value of 13 nM
      against human nNOS with 1761-fold human n/e selectivity. Compound 14j also
      displayed good metabolic stability in human liver microsomes, low plasma protein
      binding, and minimal binding to cytochromes P450 (CYPs), although it had little
      to no Caco-2 permeability.

PMID- 27050843
TI  - A Pragmatic Randomized Controlled Trial of 6-Step vs 3-Step Hand Hygiene
      Technique in Acute Hospital Care in the United Kingdom.
AB  - OBJECTIVE To evaluate the microbiologic effectiveness of the World Health
      Organization's 6-step and the Centers for Disease Control and Prevention's 3-step
      hand hygiene techniques using alcohol-based handrub. DESIGN A parallel group
      randomized controlled trial. SETTING An acute care inner-city teaching hospital
      (Glasgow). PARTICIPANTS Doctors (n=42) and nurses (n=78) undertaking direct
      patient care. INTERVENTION Random 1:1 allocation of the 6-step (n=60) or the 3
      step (n=60) technique. RESULTS The 6-step technique was microbiologically more
      effective at reducing the median log10 bacterial count. The 6-step technique
      reduced the count from 3.28 CFU/mL (95% CI, 3.11-3.38 CFU/mL) to 2.58 CFU/mL
      (2.08-2.93 CFU/mL), whereas the 3-step reduced it from 3.08 CFU/mL (2.977-3.27
      CFU/mL) to 2.88 CFU/mL (-2.58 to 3.15 CFU/mL) (P=.02). However, the 6-step
      technique did not increase the total hand coverage area (98.8% vs 99.0%, P=.15)
      and required 15% (95% CI, 6%-24%) more time (42.50 seconds vs 35.0 seconds,
      P=.002). Total hand coverage was not related to the reduction in bacterial count.
      CONCLUSIONS Two techniques for hand hygiene using alcohol-based handrub are
      promoted in international guidance, the 6-step by the World Health Organization
      and 3-step by the Centers for Disease Control and Prevention. The study provides
      the first evidence in a randomized controlled trial that the 6-step technique is
      superior, thus these international guidance documents should consider this
      evidence, as should healthcare organizations using the 3-step technique in
      practice. Infect Control Hosp Epidemiol 2016;37:661-666.

PMID- 27050844
TI  - Time to target brain atrophy and neurodegeneration in multiple sclerosis.

PMID- 27050845
TI  - Myotonic dystrophy type 1: frequency of ophthalmologic findings.
AB  - The purpose of the study was to evaluate the frequency of ophthalmologic
      abnormalities in a cohort of myotonic dystrophy type 1 (DM1) patients and to
      correlate them with motor function. We reviewed the pathophysiology of cataract
      and low intraocular pressure (IOP). Method Patients were included after clinical
      and laboratory diagnosis and after signed informed consent. They were evaluated
      by Motor Function Measure scale, Portuguese version (MFM-P) and ophthalmic
      protocol. Results We evaluated 42 patients aged 17 to 64 years (mean 40.7 +/-
      12.5), 22 of which were men. IOP (n = 41) was reduced in all but one. We found
      cataract or positivity for surgery in 38 (90.48%) and ptosis in 23 (54.76%).
      These signs but not IOP were significantly correlated with severity of motor
      dysfunction. Abnormalities in ocular motility and stereopsis were observed.
      Conclusion Cataract and ptosis are frequent in DM1 and associated to motor
      dysfunction. Reduced IOP is also common, but appears not to be related with motor
      impairment. 

PMID- 27050846
TI  - Dissociative experiences in patients with epilepsy.
AB  - A few studies have explored dissociative experiences in epilepsy patients. We
      investigated dissociative experiences in patients with epilepsy using the
      dissociative experiences scale (DES). Ninety-eight patients with epilepsy and
      sixty healthy controls were enrolled in this study. A sociodemographic
      questionnaire and the Dissociative Experiences Scale (DES), Beck Depression
      Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered to the
      participants. The DES scores were significantly higher for the patients with
      epilepsy than the healthy individuals. The number of individuals with
      pathological dissociation (DES >= 30) was higher in the epilepsy group (n = 28)
      than in the control group (n = 8). Also, higher levels of dissociation were
      significantly associated with frequency of seizures, but were not associated with
      duration of epilepsy and age at onset of the disorder. These findings demonstrate
      that patients with epilepsy are more prone to dissociation than controls. The
      high rate of dissociative experiences among patients with epilepsy suggest that
      some epilepsy-related factors are present. 

PMID- 27050847
TI  - Temporomandibular disorders in fibromyalgia patients: are there different pain
      onset?
AB  - OBJECTIVE: To identify temporomandibular disorders (TMD) symptoms in two groups
      of fibromyalgia patients according to the temporal relation between the onset of
      facial pain (FP) and generalized body pain (GBP). CROSS-SECTIONAL STUDY DESIGN:
      Fifty-three consecutive women with fibromyalgia and FP were stratified according
      to the onset of orofacial pain: Group-A (mean age 47.30 +/- 14.20 years old),
      onset of FP preceded GBP; Group-B (mean age 51.33 +/- 11.03 years old), the FP
      started concomitant or after GBP. CLINICAL ASSESSMENT: Research Diagnostic
      Criteria for Temporomandibular Disorders and the Visual Analogue Scale. RESULTS:
      Myofascial pain with mouth opening limitation (p = 0.038); right disc
      displacement with reduction (p = 0.012) and jaw stiffness (p = 0.004) were
      predominant in Group A. Myofascial pain without mouth opening limitation (p =
      0.038) and numbness/burning were more common in Group B. CONCLUSION: All patients
      had temporomandibular joint symptoms, mainly muscle disorders. The prevalence of
      myofascial pain with limited mouth opening and right TMJ disc displacement with
      reduction were higher in Group A.

PMID- 27050848
TI  - The prevalence of developmental dyscalculia in Brazilian public school system.
AB  - The goal of the study was to assess public school children at the end of the
      first stage of elementary school. We used a protocol applied concurrently with a
      writing test in the form of an unexpected activity in 28 public schools; 2,893
      children assessed, 687 exhibited performance below 58 points, 184 were excluded
      due to change of address or lack of consent; 503 children subjected to a test of
      intellectual capacity and reading assessment and 71 considered intellectually
      disabled were excluded. 226 (7.8%) children, who could read, write, and had
      normal intellectual level, met the criteria of developmental dyscalculia (DD), 98
      female and 128 male. The most influential factors in the prevalence were
      socioeconomic levels of the schools neighborhood, education level of parents, and
      being male, as demonstrated by the odds ratio and multiple logistic regression
      analysis. Further studies should be done so that educational policies are taken. 

PMID- 27050849
TI  - Pain, depression and sleep disorders in patients with diabetic and nondiabetic
      carpal tunnel syndrome: a vicious cycle.
AB  - Carpal tunnel syndrome (CTS) is a condition involving nerve entrapment that often
      leads to chronic neuropathic pain. We aimed to evaluate sleep quality and related
      parameters in diabetic and non-diabetic CTS patients. METHOD: This study included
      a total of 366 patients with chronic CTS. These patients' sleep quality was
      evaluated using the Pittsburgh Sleep Quality Index (PSQI) and depression using
      the Beck Depression Inventory (BDI). The severity of neuropathic pain was
      evaluated using the Douleur Neuropathique-4 (DN4) questionnaire and a visual
      analogue scale (VAS). RESULTS: In the non-diabetic patient group, the total PSQI
      score was found to affect BDI and VAS, while in the diabetic patient group, the
      duration of symptoms affected VAS, BDI and fasting glucose levels. CONCLUSION:
      For diabetic patients, hyperglycemia depression and chronification of neuropathic
      pain may lead to deterioration of sleep quality. Therefore, consideration of
      these parameters in the treatment may break a vicious cycle.

PMID- 27050850
TI  - Carotid artery stenting in the context of endovascular treatment of acute
      ischemic stroke.
AB  - Mechanical thrombectomy as an adjunctive to intravenous thrombolysis is now the
      standard treatment for acute ischemic stroke (AIS) due to large vessel
      occlusions. However, the best management of acute carotid tandem occlusions (CTO)
      remains controversial. METHOD: Twenty patients underwent endovascular treatment
      of acute CTO. The primary endpoint was the composite rate of complete or partial
      recanalization without a symptomatic intracranial hemorrhage (sICH). Secondary
      endpoints were recanalization times, procedure times, and clinical outcomes at
      three months. RESULTS: The primary endpoint was reached in 17 (85%) patients.
      Recanalization rate was reached in 90% of patients (19/20) and sICH rate was 5%
      (1/20). At the 3-month follow-up we obtained a mRS <= 2 rate of 35% (7/20) and a
      mortality rate of 20% (4/20). CONCLUSION: Carotid angioplasty stenting and
      endovascular treatment of AIS due to CTO appears effective with an acceptable
      rate of sICH.

PMID- 27050851
TI  - Left atrial appendage occlusion with Amplatzer Cardio Plug is an acceptable
      therapeutic option for prevention of stroke recurrence in patients with non
      valvular atrial fibrillation and contraindication or failure of oral
      anticoagulation with acenocumarol.
AB  - Left atrial appendage occlusion (LAAO) appears as a therapeutic option for some
      atrial fibrillation patients not suitable for oral anticoagulation because an
      increased hemorrhagic risk or recurrent ischemic events despite anticoagulant
      treatment. METHODS: Report of consecutive atrial fibrillation patients treated
      with LAAO with Amplatzer Cardio Plug because contraindication or failure of oral
      anticoagulation with acenocumarol. CHA2DS2VASC, HAS-BLED, NIHSS, mRS, procedural
      complications and outcome were assessed. Seven patients (73 +/- 6 year-old) were
      treated after intracerebral (n = 5) and gastrointestinal (n = 1) hemorrhages or
      ischemic stroke recurrence while on acenocumarol (n = 1). RESULTS: Mean follow up
      was 18 months. Baseline CHA2DS2Vasc y HAS-BLED scores were 5.6 +/- 0.7 and 4.1 +/
      0.3 respectively. There were no strokes or deaths. There was only one non
      serious adverse event. CONCLUSION: LAAO with ACP appears as a feasible
      therapeutic option for stroke prevention in patients with atrial fibrillation and
      failure or contraindication to acenocumarol.

PMID- 27050852
TI  - Activation of C-fiber nociceptors by low-power diode laser.
AB  - OBJECTIVE: The evaluation of selective activation of C-fibers to record evoked
      potentials using the association of low-power diode laser (810 nm), tiny-area
      stimulation and skin-blackening. METHOD: Laser-evoked potentials (LEPs) were
      obtained from 20 healthy young subjects. An aluminum plate with one thin hole was
      attached to the laser probe to provide tiny-area stimulation of the hand dorsum
      and the stimulated area was covered with black ink. RESULTS: The mean intensity
      used for eliciting the ultra-late laser-evoked potential (ULEP) was 70 +/- 32 mW.
      All subjects showed a clear biphasic potential that comprised a negative peak
      (806 +/- 61 ms) and a positive deflection (1033 +/- 60 ms), corresponding to the
      ULEP related to C-fiber activation. CONCLUSION: C-fiber-evoked responses can be
      obtained using a very low-power diode laser when stimulation is applied to tiny
      areas of darkened skin. This strategy offers a non-invasive and easy methodology
      that minimizes damage to the tissue.

PMID- 27050853
TI  - Orbitozygomatic craniotomy in three pieces: tips and tricks.
AB  - OBJECTIVE: Didactically describe the orbitozygomatic craniotomy made in three
      pieces. METHOD: This approach was performed, from 2002 to 2011, in 49 patients
      admitted at Beneficencia Portuguesa of Sao Paulo Hospital. RESULTS: Twenty-seven
      patients had vascular lesions and twenty-two suffered for intracranial skull base
      tumors. The vascular lesions varied from cavernous angiomas inside the
      mesencephalum, high bifurcation basilar tip aneurysms, superior cerebellar
      arteries aneurysms and arteriovenous malformations in the interpeduncular
      cistern. Skull base tumors as meningiomas, interpeduncular hamartomas and third
      ventricle floor gliomas were among the neoplastic lesions approached. We had no
      permanent injuries and minimal transient complications had occurred. CONCLUSION:
      It is a descriptive text, organized in the sequence of the main stages in which
      such a craniotomy is performed, describing in details the technique in which this
      group of evolutionarily authors came to accomplish the task.

PMID- 27050854
TI  - Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact.
AB  - Multiple sclerosis (MS) was always considered as a white matter inflammatory
      disease. Today, there is an important body of evidence that supports the
      hypothesis that gray matter involvement and the neurodegenerative mechanism are
      at least partially independent from inflammation. Gray matter atrophy develops
      faster than white matter atrophy, and predominates in the initial stages of the
      disease. The neurodegenerative mechanism creates permanent damage and correlates
      with physical and cognitive disability. In this review we describe the current
      available evidence regarding brain atrophy and its consequence in MS patients. 

PMID- 27050856
TI  - Guillain-Barre syndrome associated with the Zika virus outbreak in Brazil.
AB  - Zika virus (ZIKV) is now considered an emerging flavivirosis, with a first large
      outbreak registered in the Yap Islands in 2007. In 2013, a new outbreak was
      reported in the French Polynesia, with associated cases of neurological
      complications including Guillain-Barre syndrome (GBS). The incidence of GBS has
      increased in Brazil since 2015, what is speculated to be secondary to the ZIKV
      infection outbreak. The gold-standard test for detection of acute ZIKV infection
      is the polymerase-chain reaction technique, an essay largely unavailable in
      Brazil. The diagnosis of GBS is feasible even in resource-limited areas using the
      criteria proposed by the GBS Classification Group, which is based solely on
      clinical grounds. Further understanding on the relationship of ZIKV with
      neurological complications is a research urgency. 

PMID- 27050855
TI  - Current concepts in the treatment of hereditary ataxias.
AB  - Hereditary ataxias (HA) represents an extensive group of clinically and
      genetically heterogeneous neurodegenerative diseases, characterized by
      progressive ataxia combined with extra-cerebellar and multi-systemic
      involvements, including peripheral neuropathy, pyramidal signs, movement
      disorders, seizures, and cognitive dysfunction. There is no effective treatment
      for HA, and management remains supportive and symptomatic. In this review, we
      will focus on the symptomatic treatment of the main autosomal recessive ataxias,
      autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial
      ataxias. We describe management for different clinical symptoms, mechanism-based
      approaches, rehabilitation therapy, disease modifying therapy, future clinical
      trials and perspectives, genetic counseling and preimplantation genetic
      diagnosis. 

PMID- 27050857
TI  - Neurophysiological and neuroimaging changes (crossed cerebrocerebellar atrophy)
      after prolonged non-convulsive status epilepticus.

PMID- 27050858
TI  - MELAS or more.

PMID- 27050860
TI  - Erratum.

PMID- 27050859
TI  - Recommendations for the treatment of migraine attacks - a Brazilian consensus.
AB  - In this article, a group of experts in headache management of the Brazilian
      Headache Society developed through a consensus strategic measurements to treat a
      migraine attack in both the child and the adult. Particular emphasis was laid on
      the treatment of migraine in women, including at pregnancy, lactation and
      perimenstrual period. 

PMID- 27050861
TI  - Inhibition of proprotein convertase subtilisin/kexin type 9 in the treatment of
      hypercholesterolemia.

PMID- 27050863
TI  - Site-Specific Albumination as an Alternative to PEGylation for the Enhanced Serum
      Half-Life in Vivo.
AB  - Polyethylene glycol (PEG) has been widely used as a serum half-life extender of
      therapeutic proteins. However, due to immune responses and low degradability of
      PEG, developing serum half-life extender alternatives to PEG is required. Human
      serum albumin (HSA) has several beneficial features as a serum half-life
      extender, including a very long serum half-life, good degradability, and low
      immune responses. In order to further evaluate the efficacy of HSA, we compared
      the extent of serum half-life extension of a target protein, superfolder green
      fluorescent protein (sfGFP), upon HSA conjugation with PEG conjugation side-by
      side. Combination of site-specific incorporation of p-azido-l-phenylalanine into
      sfGFP and copper-free click chemistry achieved the site-specific conjugation of a
      single HSA, 20 kDa PEG, or 30 kDa PEG to sfGFP. These sfGFP conjugates exhibited
      the fluorescence comparable to or even greater than that of wild-type sfGFP
      (sfGFP-WT). In mice, HSA-conjugation to sfGFP extended the serum half-life 9.0
      times compared to that of unmodified sfGFP, which is comparable to those of PEG
      conjugated sfGFPs (7.3 times for 20 kDa PEG and 9.5 times for 30 kDa PEG). These
      results clearly demonstrated that HSA was as effective as PEG in extending the
      serum half-life of a target protein. Therefore, with the additional favorable
      features, HSA is a good serum half-life extender of a (therapeutic) protein as an
      alternative to PEG.

PMID- 27050864
TI  - Ameliorative effect of naringin in acetaminophen-induced hepatic and renal
      toxicity in laboratory rats: role of FXR and KIM-1.
AB  - CONTEXT: Acetaminophen (APAP) is an analgesic and antipyretic agent commonly
      known agent to cause hepatic and renal toxicity at a higher dose. Naringin, a
      bioflavonoid possesses multiple pharmacological properties such as antioxidant,
      anti-inflammatory, analgesic and anti-hyperlipidemic activity. OBJECTIVE: To
      evaluate the effect of naringin against the APAP-induced hepatic and renal
      toxicity. MATERIALS AND METHODS: Male Wistar albino rats (180-220 g) were divided
      into various groups, and toxicity was induced by APAP (700 mg/kg, p.o., 14 days).
      Naringin (20, 40 and 80 mg/kg, p.o.) or Silymarin (25 mg/kg) was administered to
      rats 2 h before APAP oral administration. Various biochemical, molecular and
      histopathological parameter were accessed in hepatic and renal tissue. RESULTS:
      Naringin pretreatment significantly decreased (p < 0.05) serum creatinine, blood
      urea nitrogen, bilirubin, aspartate transaminase, alanine transaminase, lactate
      dehydrogenase, low-density lipoprotein, very low-density lipoprotein, cholesterol
      and triglycerides as compared with APAP control rats. Decreased level of serum
      albumin, uric acid, and high-density lipoprotein were also significantly restored
      (p < 0.05) by naringin pretreatment. It also significantly restores (p < 0.05)
      the altered level of superoxide dismutase, reduced glutathione, malondialdehyde
      and nitric oxide in hepatic and renal tissue. Moreover, altered mRNA expression
      of hepatic farnesoid X receptor and renal injury molecule-1 (KIM-1) were
      significantly restored (p < 0.05) by naringin treatment. Naringin treatment also
      reduced histological alteration induced by APAP in the liver and kidney.
      CONCLUSION: Naringin exerts its hepato- and nephroprotective effect via
      modulation of oxido-nitrosative stress, FXR and KIM-1 mRNA expression.

PMID- 27050865
TI  - Drying techniques of probiotic bacteria as an important step towards the
      development of novel pharmabiotics.
AB  - The increasing knowledge about the human microbiome leads to the awareness of how
      important probiotics can be for our health. Although further substantiation is
      required, it appears that several pathologies could be treated or prevented by
      the administration of pharmaceutical formulations containing such live health
      beneficial bacteria. These pharmabiotics need to provide their effects until the
      end of shelf life, which can be optimally achieved by drying them before further
      formulation. However, drying processes, including spray-, freeze-, vacuum- and
      fluidized bed drying, induce stress on probiotics, thus decreasing their
      viability. Several protection strategies can be envisaged to enhance their
      viability, including addition of protective agents, controlling the process
      parameters and prestressing the probiotics prior to drying. Moreover, probiotic
      viability needs to be maintained during long-term storage. Overall, lower storage
      temperature and low moisture content result in good survival rates. Attention
      should also be given to the rehydration conditions of the dried probiotics, as
      this can exert an important effect on their revival. By describing not only the
      characteristics, but also the viability results obtained by the most relevant
      drying techniques in the probiotic industry, we hope to facilitate the deliberate
      choice of drying process and protection strategy for specific probiotic and
      pharmabiotic applications. 

PMID- 27050866
TI  - Ear Cubes for local controlled drug delivery to the inner ear.
AB  - A new type of advanced drug delivery systems is proposed: Miniaturized implants,
      which can be placed into tiny holes drilled into (or close to) the oval window.
      They consist of two parts: 1) A cylinder, which is inserted into the hole
      crossing the oval window. The cylinder (being longer than the depth of the hole)
      is partly located within the inner ear and surrounded by perilymph. This provides
      direct access to the target site, and at the same time assures implant fixation.
      2) A cuboid, which is located in the middle ear, serving as a drug reservoir. One
      side of the cuboid is in direct contact with the oval window. Drug release into
      the cochlea occurs by diffusion through the cylindrical part of the Ear Cubes and
      by diffusion from the cuboid into and through the oval window. High precision
      molds were used to prepare two differently sized Ear Cubes by injection molding.
      The miniaturized implants were based on silicone and loaded with different
      amounts of dexamethasone (10 to 30 % w/w). The systems were thoroughly
      characterized before and upon exposure to artificial perilymph at 37 degrees C.
      Importantly, drug release can effectively be controlled and sustained during long
      time periods (up to several years). Furthermore, the implants did not swell or
      erode to a noteworthy extent during the observation period. Drug diffusion
      through the polymeric matrix, together with limited dexamethasone solubility
      effects, seem to control the resulting drug release kinetics, which can roughly
      be estimated using mathematical equations derived from Fick's second law.
      Importantly, the proposed Ear Cubes are likely to provide much more reliable
      local long term drug delivery to the inner ear compared to liquid or semi-solid
      dosage forms administered into the middle ear, due to a more secured fixation.
      Furthermore, they require less invasive surgeries and can accommodate higher drug
      amounts compared to intracochlear implants. Thus, they offer the potential to
      open up new horizons for innovative therapeutic strategies to treat inner ear
      diseases and disorders. 

PMID- 27050867
TI  - Glycoside-based niosomal nanocarrier for enhanced in-vivo performance of
      Cefixime.
AB  - This study aimed to evaluate the potential of a novel glycoside non-ionic
      surfactant synthesized and characterized in our laboratory for increased oral
      bioavailability of Cefixime. The surfactant was synthesized by simple
      etherification of bergenin with bromoundecane and characterized by (1)H NMR and
      mass spectroscopy (MS). Biocompatibility of the surfactant (BRM-BG) was assessed
      by in-vitro cytotoxicity against NIH/3T3 cells and human blood hemolysis. In-vivo
      acute toxicity was evaluated in mices. Cefixime loaded BRM-BG niosomes were
      investigated for drug entrapment efficiency using HPLC and surface morphology and
      vesicle size by atomic force microscopy (AFM) and dynamic light scattering (DLS).
      The in-vivo oral bioavailability and pharmacokinetics studies were carried out
      using rabbits. Cefixime loaded BRM-BG vesicles were spherical in the size range
      of 178.66+/-8.17nm with a polydipersity index (PDI) of 0.20+/-0.01, offering an
      entrapment efficiency as high as 78.4+/-0.83%. When the surfactant was applied on
      NIH 3T3 tissue culture, as high as 90.77+/-3.15% and 86.86+/-3.02%, cell
      viability at 1000MUg/mL concentration after 24 and 48h respectively were
      observed. The surfactant also caused 5.49+/-1.62% haemolysis and was found to be
      safe at a dose up to 2000mg/kg. In-vivo drug plasma concentration (Cmax) was
      found to be 9.69+/-1.22MUg/mL, much higher than that resulting from the intake of
      commercial suspension and capsules. BRM-BG demonstrated to be safe and effective
      as carrier of Cefixime following oral dosing in rabbits. The BRM-BG surfactant
      delivery nano-system is relatively safe and in animal models it is an appropriate
      carrier for Cefixime, offering enhanced bioavailability compared to commercially
      available formulations of the drug. 

PMID- 27050868
TI  - To what extent is foot pain related to biomechanical changes and ultrasound
      detected abnormalities in rheumatoid arthritis?
AB  - OBJECTIVES: To investigate the presence of biomechanical abnormalities and
      ultrasound (US)-detected inflammation and damage in low disease or remission
      status rheumatoid arthritis (RA) patients with foot complaints. METHODS: We
      recruited 136 subjects with foot complaints. Sixty-two were biologic disease
      modifying antirheumatic drug-treated RA patients presenting Disease Activity
      Score-determined remission or low disease activity while the remaining 74 were
      gender matched controls without rheumatic or musculoskeletal disorders. Both
      groups underwent a comprehensive podiatric, biomechanical and B-mode and Doppler
      US assessment of the feet. RESULTS: Most RA patients and controls were female
      (77.4% and 83.8%, respectively). There was no statistical difference in the
      proportion of obese subjects in either group (p=0.792). Inappropriate shoes were
      used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia,
      particularly heel pain, was more frequent in the control group, with associated
      talalgia and metatarsalgia being more prevalent in the RA group (p<0.05). The RA
      patient group was also more likely to present greater foot deformity, more
      limited joint movement and biomechanical abnormalities than the controls
      (p<0.05). US inflammatory and structural changes were significantly more frequent
      in RA patients than in controls (p<0.05). US structural involvement was
      significantly associated with limited joint mobility and pathologic biomechanical
      tests only in RA patients (p<0.05). CONCLUSIONS: RA foot complaints seemed to be
      linked to US-detected RA involvement and biomechanical abnormalities. Podiatric
      and US assessments can be useful to help the clinician to optimise the management
      of RA patients in remission/low disease activity with foot complaints.

PMID- 27050869
TI  - Testosterone Attenuates Age-Related Fall in Aerobic Function in Mobility Limited
      Older Men With Low Testosterone.
AB  - CONTEXT: Testosterone increases skeletal muscle mass and strength, but the
      effects of testosterone on aerobic performance in mobility-limited older men have
      not been evaluated. OBJECTIVE: To determine the effects of testosterone
      supplementation on aerobic performance, assessed as peak oxygen uptake (VO2peak)
      and gas exchange lactate threshold (VO2theta), during symptom-limited incremental
      cycle ergometer exercise. DESIGN: Subgroup analysis of the Testosterone in Older
      Men with Mobility Limitations Trial. SETTING: Exercise physiology laboratory in
      an academic medical center. PARTICIPANTS: Sixty-four mobility-limited men 65
      years or older with low total (100-350 ng/dL) or free (<50 pg/dL) testosterone.
      INTERVENTIONS: Participants were randomized to receive 100-mg testosterone gel or
      placebo gel daily for 6 months. MAIN OUTCOME MEASURES: VO2peak and VO2theta from
      a symptom-limited cycle exercise test. RESULTS: Mean (SD) baseline VO2peak was
      20.5 (4.3) and 19.9 (4.7) mL/kg/min for testosterone and placebo, respectively.
      VO2peak increased by 0.83 (2.4) mL/kg/min in testosterone but decreased by -0.89
      (2.5) mL/kg/min in placebo (P = .035); between group difference in change in
      VO2peak was significant (P = .006). This 6-month reduction in placebo was greater
      than the expected -0.4-mL/kg/min/y rate of decline in the general population.
      VO2theta did not change significantly in testosterone but decreased by 1.1 (1.8)
      mL/kg/min in placebo, P = .011 for between-group comparisons. Hemoglobin
      increased by 1.0 +/- 3.5 and 0.1 +/- 0.8 g/dL in testosterone and placebo groups,
      respectively. CONCLUSION: Testosterone supplementation in mobility-limited older
      men increased hemoglobin and attenuated the age-related declines in VO2peak and
      VO2theta. Long-term intervention studies are needed to determine the durability
      of this effect.

PMID- 27050870
TI  - Irreversible airway obstruction in asthma: A risk factor for severe exacerbations
      in spite of proper treatment.
AB  - OBJECTIVES: To evaluate whether irreversible airway obstruction (IAO) related to
      asthma is a risk factor for lack of symptoms control, poor quality of life and
      exacerbations. METHODS: We evaluated consecutive outpatients with asthma in a one
      year cohort study. We excluded subjects with smoke history > 9 pack-years.
      Definition of IAO was post bronchodilator FEV1/CVF ratio below the lower limit of
      normality. Subjects received high dose of inhaled medications for asthma. We used
      logistic regression models, adjusted for the treatment offered during the study,
      to evaluate whether IAO related to asthma is a risk factor for symptoms control,
      quality of life, any emergency room visit, number of emergency room visits and
      hospital admission. RESULTS: We enrolled 248 subjects in the study. IAO was not a
      risk factor for poor symptoms control [OR 1.354, 95 CI (0.632-2.899)] or worse
      asthma related quality of life [OR 0.705, 95 CI (0.413-1.204)]. Subjects with IAO
      had higher odds of any emergency room visit [OR 2.214, 95 CI (1.300-3.768)] and
      hospital admission [OR 8.530, 95 CI (1.517-47.978)] and lower odds to reduce
      emergency room visits in the course of the follow-up period [OR 0.452, 95 CI
      (0.265-0.769)]. IAO did not predict the number of emergency room visits [OR 1.53,
      95 CI (0.71-3.30). CONCLUSION: IAO is not a risk factor for poor symptoms control
      or poor quality of life, in a setting of proper treatment. It is a risk factor
      for emergency room visit and hospital admission. Subjects with IAO have poor
      response to treatment.

PMID- 27050871
TI  - Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled
      analysis.
AB  - BACKGROUND: Gastro-oesophageal reflux disease is a potential risk factor for the
      development and progression of idiopathic pulmonary fibrosis (IPF). We aimed to
      investigate the effect of antacid therapy on disease progression in patients
      randomly assigned to placebo through analysis of three large, phase 3 trials of
      pirfenidone in IPF. METHODS: Patients with IPF from the placebo groups of three
      trials of pirfenidone (CAPACITY 004, CAPACITY 006, and ASCEND) were included in
      this post-hoc analysis. We analysed effects of antacid therapy use from baseline
      for pulmonary function, exercise tolerance, survival, hospital admission, and
      adverse events for 52 weeks with and without adjustment for potential
      confounders. The primary endpoint, disease progression by 1 year, was defined as
      a decrease in predicted forced vital capacity (FVC) by 10% or more, a decrease in
      6 min walk distance (6MWD) by 50 m or more, or death. We did survival analyses
      with the Kaplan-Meier estimator and evaluated using the log-rank test. FINDINGS:
      Of 624 patients, 291 (47%) received antacid therapy and 333 (53%) did not. At 52
      weeks, we noted no significant difference between groups for disease progression
      (114 [39%] for antacid therapy vs 141 [42%] for no antacid therapy, p=0.4844).
      Rates also did not differ for all-cause mortality (20 [7%] vs 22 [7%], p=0.8947),
      IPF-related mortality (11 [4%] vs 17 [5%]; p=0.4251), absolute FVC decrease by
      10% or more (49 [17%] vs 64 [19%]; p=0.4411), or mean observed change in FVC (%
      predicted -4.9% [SD 6.4] vs -5.5% [7.2], p=0.3355; observed volume -0.2 L [0.3]
      vs -0.2 L [0.3], p=0.4238). The rate of hospital admission was non-significantly
      higher in the antacid therapy group (65 [22%] vs 54 [16%]; p=0.0522). When
      stratified by baseline FVC (<70% or >=70%), disease progression, mortality, FVC,
      6MWD, and hospital admission did not differ between groups. Adverse events were
      similar between treatment and no treatment groups; however, overall infections
      (107 [74%] vs 101 [62%]; p=0.0174) and pulmonary infections (20 [14%] vs 10 [6%];
      p=0.0214) were higher in patients with advanced IPF (ie, FVC <70%) who were
      treated with antacids than not treated with antacids. INTERPRETATION: Antacid
      therapy did not improve outcomes in patients with IPF and might potentially be
      associated with an increased risk of infection in those with advanced disease.
      FUNDING: F Hoffmann-La Roche.

PMID- 27050872
TI  - Early versus late parenteral nutrition in critically ill children.

PMID- 27050873
TI  - Antacid therapy and idiopathic pulmonary fibrosis: cause for heartburn?

PMID- 27050874
TI  - Impact of the Electron-Phonon Interactions on the Polaron Dynamics in Graphene
      Nanoribbons.
AB  - The influence of the electron-phonon (e-ph) interactions on the filed-included
      polaron dynamics in armchair graphene nanoribbons (GNRs) is theoretically
      investigated in the scope of a two-dimensional tight-binding model. The results
      show that the localization of the polaronic charge increases when the strength of
      e-ph coupling also increases. Consequently, the polaron saturation velocity
      decreases for higher e-ph coupling strengths. Interestingly, the interplay
      between the e-ph coupling strength and the GNR width changes substantially the
      polaron dynamics properties. 

PMID- 27050875
TI  - Mitigation of reversible self-association and viscosity in a human IgG1
      monoclonal antibody by rational, structure-guided Fv engineering.
AB  - Undesired solution behaviors such as reversible self-association (RSA), high
      viscosity, and liquid-liquid phase separation can introduce substantial
      challenges during development of monoclonal antibody formulations. Although a
      global mechanistic understanding of RSA (i.e., native and reversible protein
      protein interactions) is sufficient to develop robust formulation controls, its
      mitigation via protein engineering requires knowledge of the sites of protein
      protein interactions. In the study reported here, we coupled our previous
      hydrogen-deuterium exchange mass spectrometry findings with structural modeling
      and in vitro screening to identify the residues responsible for RSA of a model
      IgG1 monoclonal antibody (mAb-C), and rationally engineered variants with
      improved solution properties (i.e., reduced RSA and viscosity). Our data show
      that mutation of either solvent-exposed aromatic residues within the heavy and
      light chain variable regions or buried residues within the heavy chain/light
      chain interface can significantly mitigate RSA and viscosity by reducing the
      IgG's surface hydrophobicity. The engineering strategy described here highlights
      the utility of integrating complementary experimental and in silico methods to
      identify mutations that can improve developability, in particular, high
      concentration solution properties, of candidate therapeutic antibodies.

PMID- 27050876
TI  - Forkhead box A1 (FOXA1) tagging polymorphisms and esophageal cancer risk in a
      Chinese population: a fine-mapping study.
AB  - Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth
      leading cause of cancer-related death in China in 2009. Esophageal squamous cell
      carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Besides
      environmental risk factors, genetic factors such as single-nucleotide
      polymorphisms (SNPs) play an important role in ESCC carcinogenesis. We performed
      a hospital-based case-control study to evaluate the Forkhead-box protein A1
      (FOXA1) rs12894364 C > T, rs2145146 C > A and rs7144658 T > C tag SNPs in the
      risk of developing ESCC. We recruited 629 ESCC cases and 686 controls. Genotypes
      were determined using ligation detection reaction. Logistic regression analyses
      revealed that the three FOXA1 SNPs were not associated with ESCC risk. However,
      there was significantly decreased ESCC risk associated with the FOXA1 rs12894364
      C > T and rs2145146 C > A polymorphisms among older patients. There was
      significantly increased ESCC risk associated with the FOXA1 rs7144658 T > C
      polymorphism among male patients. This study demonstrates an association between
      FOXA1 polymorphisms and ESCC susceptibility. Additional larger studies are
      required to confirm our findings. 

PMID- 27050877
TI  - Evangelical Protestants and the ACA: An Opening for Community-Based Primary Care?
AB  - Evangelical Protestants make up the largest religious subgroup in the United
      States, and previous research has shown that Evangelical churches are
      disproportionately active in community engagement and efforts toward social
      change. Although Evangelical Protestant perspectives have been considered with
      regard to persistent socioeconomic stratification and racial discrimination, less
      focus has been given to how churches interpret poor health outcomes within the
      United States. In particular, this research addresses how enduring health
      disparities are understood within the larger discussion of healthcare reform. Due
      to the similarity of approaches favored by participants in this study and
      community-based philosophy, a suggestion is made for future health policy
      dialogue. Although Evangelical Protestants have been most likely to reject all
      aspects of the Affordable Care Act, in many ways the findings of this study
      suggest the potential for successful future health policy collaboration. In
      particular, community-based primary care might appeal to Evangelicals and health
      professionals in the ongoing effort to improve population health and the quality
      of healthcare in the United States.

PMID- 27050878
TI  - High-Risk Corneal Graft Rejection in the Setting of Previous Corneal Herpes
      Simplex Virus (HSV)-1 Infection.
AB  - PURPOSE: The "high-risk phenotype" of corneal graft recipients is considered to
      be related to preexisting vascularization such as that associated with herpes
      simplex virus-1 (HSV-1) keratitis (HSK). The purpose of this study was to
      investigate the immunologic mechanisms underlying accelerated corneal graft
      rejection using a mouse model of HSK. METHODS: Herpes simplex virus type 1
      keratitis was induced in BALB/c mice. Syngeneic and allogeneic (C57BL/6 mice)
      corneal grafts were performed in mice with HSK at different times after
      infection. Some grafts were performed on HSV-infected CD4 T cell-deficient BALB/c
      mice. Clinical, histologic, immunologic, and virus detection studies were
      performed on samples of cornea, draining lymph node (LN), and trigeminal ganglion
      (TG) cells. RESULTS: Corneal grafts in mice with HSK rejected with higher
      frequency and more rapid tempo compared with grafts in uninfected mice. In
      corneas with HSK and vascularization at the time of grafting, both syngeneic and
      allogeneic corneal grafts failed with similar frequency and tempo. However, in
      the absence of preexisting inflammation and vascularization, syngeneic grafts
      were accepted when the grafts were performed at a late time point after HSV
      infection (42 days), whereas allografts were rejected at this time. In contrast,
      syngeneic grafts in nonvascularized HSV-infected recipients failed if they were
      performed within 10 days of HSV infection, an effect that was dependent on CD4 T
      cells, as demonstrated using CD4 deficient mice. Importantly, a variably
      sustained but strongly positive anti-HSV T-cell response was detected in
      allografted HSK recipients with a similar but lesser response in syngeneic hosts.
      CONCLUSIONS: A previous HSV-1 corneal infection predisposes donor grafts to a
      high risk of failure by both innate and adaptive immune mechanisms in which an
      anti-HSV CD4 T-cell response plays a prominent role.

PMID- 27050879
TI  - Restoration of Cone Interdigitation Zone Associated With Improvement of Focal
      Macular ERG After Fovea-Off Rhegmatogenous Retinal Reattachment.
AB  - PURPOSE: To determine whether a correlation exists between the parameters of the
      focal macular ERGs (FMERGs) and the microstructural changes of the photoreceptors
      after successful surgery for fovea-off rhegmatogenous retinal detachment (RRD).
      METHODS: Twenty eyes of 20 patients who had undergone successful surgery to
      reattach the retina in eyes with fovea-off RRD were studied. Focal macular ERGs
      and spectral-domain OCT (SD-OCT) were recorded at 1 and 6 months after the
      surgery. Changes of the components of the FMERGs, as well as changes of the SD
      OCT parameters including the length of the external limiting membrane (ELM),
      ellipsoid zone (EZ), cone interdigitation zone (CIZ), and size of the outer
      photoreceptor area (between ELM and RPE), were determined. RESULTS: During the
      postoperative period, the mean amplitudes of the a-waves increased by 1.4 times
      and the b-waves by 1.7 times. Spectral-domain OCT showed that the mean length of
      the EZ and CIZ and the size of the outer photoreceptor area had increased
      significantly at 6 months. The degree of the increase in the CIZ and outer
      photoreceptor area was significantly correlated with the increase in the
      amplitudes of the b-waves of the FMERGs (r = 0.56, P = 0.042, r = 0.57, P =
      0.040, respectively; Spearman rank correlation test). However, the length of the
      EZ was not significantly correlated with the increase of the b-waves.
      CONCLUSIONS: A restoration of the EZ alone might not be enough to improve the
      FMERGs, and a restoration of the EZ accompanied by that of the CIZ was essential
      for the recovery of the FMERGs after fovea-off RRD.

PMID- 27050880
TI  - Deficient Binocular Combination of Second-Order Stimuli in Amblyopia.
AB  - PURPOSE: Sensory imbalances in humans with amblyopia have been well documented
      using luminance-modulated (first-order) stimuli. However, little is known
      regarding whether there is a deficient binocular combination in amblyopes for
      stimuli defined by modulations in contrast (second-order stimuli). To address
      this, we asked two questions: Does a sensory imbalance also exist in the
      binocular combination of second-order stimuli, and if so, is it more severe than
      that expected on the basis of the imbalance for first-order stimuli? METHODS: The
      sensory imbalances of 14 adult amblyopes (mean age: 30.5 +/- 11.5 years; 5 with
      strabismus and 9 without) were measured using a dichoptic phase combination task.
      Three types of second-order dichoptic stimulus pairs were used in the study,
      where the carriers in the two eyes were either correlated, anticorrelated, or
      uncorrelated. Results were compared with those obtained using first-order stimuli
      in all observers. RESULTS: We found that second-order binocular combination in
      amblyopes was not affected by the interocular carrier correlations. The amblyopic
      eye's contribution to the binocularly fused percept was much less than that of
      the nonamblyopic eye. The resulting sensory imbalance in binocular combination
      for second-order images was comparable to that for first-order images in 8 of the
      observers but was more severe in the other 6 amblyopes. CONCLUSIONS: These
      results indicate that amblyopia does not disrupt the normal architecture of
      binocular combination for second-order signals; however, there is an additional
      deficit in binocular combination of second-order image in some amblyopes that
      cannot be fully accounted for by the known first-order sensory imbalance.

PMID- 27050881
TI  - Imaging before transfer to designated pediatric trauma centers exposes children
      to excess radiation.
AB  - BACKGROUND: Pediatric trauma patients transferred to pediatric trauma centers
      (PTCs) often have imaging at the originating hospital (OH). The increased use of
      computed tomography (CT) raises concerns about malignancy risk from ionizing
      radiation leading many PTCs to adopt radiation dose reduction strategies. We
      hypothesized that pediatric trauma patients are exposed to excess radiation from
      imaging before transfer. METHODS: A retrospective review of 1,383 scans was
      performed on all trauma patients with CT imaging before transfer to our Level I
      PTC from 2010 to 2014. Demographics, type of imaging, necessity for repeat
      imaging, appropriateness of imaging, and radiation dose delivered were recorded.
      Comparative radiation dosing was calculated using the dose-length product (DLP
      [expressed in mGy-cm]). All CT scans except for CT of the abdomen and pelvis and
      CT of the head were excluded for complete DLP data issues. Scans were considered
      clinically appropriate if they met Advanced Trauma Life Support (ATLS)
      recommendations (ATLS+) and not indicated if they did not meet ATLS criteria
      (ATLS-). Some scans were repeated because of technical issues. Median DeltaDLP
      represents the difference in dose patients received at OH versus at PTC. RESULTS:
      A total of 673 patients were analyzed. Average age was 11 years, and 65.4% were
      male. Mean DLP at PTC was 54% lower for all analyzed scans compared with OH (p <
      0.0001). DLP at PTC was 51% lower for CT of the abdomen and pelvis and 62% lower
      for CT of the head. Children received excess dose of 578.62 mGy-cm for scans at
      OH that were unnecessary. For ATLS+ imaging, children received a median excess of
      444.42 mGy-cm of radiation at OH than they would have received had the scans been
      performed at PTCs using pediatric radiation reduction strategies. CONCLUSION:
      Pediatric trauma imaging performed at transferring institutions often does not
      adhere to ATLS recommendations and exceeds required ionizing radiation dosages.
      This study further confirms ATLS recommendations supporting prompt patient
      transfer without delay for imaging. LEVEL OF EVIDENCE: Therapeutic study, level
      IV.

PMID- 27050882
TI  - A critical literature review on primary blast thorax injury and their outcomes.
AB  - Since World War II, researchers have been interested in exploring the injury
      mechanisms involved in primary blast on the thorax by using animal model
      surrogates. These studies were mostly concerned with the finding of the lung
      injury threshold, the relationship between the physical components of the air
      blast wave, and the biological response. Studies have also been conducted to
      investigate the effect of repeated blast exposures on the injury outcome
      threshold. This has led to several injury criteria, such as the Bowen curves
      based on pressure history's characteristics or the Axelsson Chest Wall Velocity
      Predictor that used measurement from the mammals' chest wall. This article aims
      at doing a critical literature review of this specific topic.

PMID- 27050883
TI  - The AAST prospective Aortic Occlusion for Resuscitation in Trauma and Acute Care
      Surgery (AORTA) registry: Data on contemporary utilization and outcomes of aortic
      occlusion and resuscitative balloon occlusion of the aorta (REBOA).
AB  - INTRODUCTION: Aortic occlusion (AO) for resuscitation in traumatic shock remains
      controversial. Resuscitative endovascular balloon occlusion of the aorta (REBOA)
      offers an emerging alternative. METHODS: The American Association for the Surgery
      of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery
      registry prospectively identified trauma patients requiring AO from eight ACS
      Level 1 centers. Presentation, intervention, and outcome variables were collected
      and analyzed to compare REBOA and open AO. RESULTS: From November 2013 to
      February 2015, 114 AO patients were captured (REBOA, 46; open AO, 68); 80.7% were
      male, and 62.3% were blunt injured. Aortic occlusion occurred in the emergency
      department (73.7%) or the operating room (26.3%). Hemodynamic improvement after
      AO was observed in 62.3% [REBOA, 67.4%; open OA, 61.8%); 36.0% achieving
      stability (systolic blood pressure consistently >90 mm Hg, >5 minutes); REBOA, 22
      of 46 (47.8%); open OA, 19 of 68 (27.9%); p =0.014]. Resuscitative endovascular
      balloon occlusion of the aorta (REBOA) access was femoral cut-down (50%); US
      guided (10.9%) and percutaneous without imaging (28.3%). Deployment was achieved
      in Zones I (78.6%), II (2.4%), and III (19.0%). A second AO attempt was required
      in 9.6% [REBOA, 2 of 46 (4.3%); open OA, 9 of 68 (13.2%)]. Complications of REBOA
      were uncommon (pseudoaneurysm, 2.1%; embolism, 4.3%; limb ischemia, 0%). There
      was no difference in time to successful AO between REBOA and open procedures
      (REBOA, 6.6 +/- 5.6 minutes; open OA, 7.2 +/- 15.1; p = 0.842). Overall survival
      was 21.1% (24 of 114), with no significant difference between REBOA and open AO
      with regard to mortality [REBOA, 28.2% (13 of 46); open OA, 16.1% (11 of 68); p =
      0.120]. CONCLUSION: Resuscitative endovascular balloon occlusion of the aorta has
      emerged as a viable alternative to open AO in centers that have developed this
      capability. Further maturation of the American Association for the Surgery of
      Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery
      database is required to better elucidate optimal indications and outcomes. LEVEL
      OF EVIDENCE: Therapeutic/care management study, level IV.

PMID- 27050884
TI  - Shorter times to packed red blood cell transfusion are associated with decreased
      risk of death in traumatically injured patients.
AB  - BACKGROUND: Hemorrhage is a leading cause of death in traumatically injured
      patients. Currently, the importance of earlier administration of packed red blood
      cells (pRBC) to improve outcomes is limited. We evaluated the association of
      earlier pRBC administration and mortality when compared with later transfusion
      initiation. METHODS: This single-center retrospective cohort study of trauma
      patients transported by a single helicopter service from the scene of injury to
      an urban academic trauma center included patients receiving at least one unit of
      pRBC within 24 hours of hospital arrival. The final cohort included patients
      transported to the trauma center between March 11, 2010, and October 30, 2013.
      The helicopter service carries two units of pRBC for protocol-driven prehospital
      transfusion. Logistic regression was used to model odds of death, and 95%
      confidence intervals were calculated. RESULTS: The 94 patients meeting inclusion
      criteria had a mean (SD) age of 43 (19) years; 87 (93%) of 94 were white, 66
      (70%) of 94 were male, and 88(94%) of 94 sustained blunt force injuries. Median
      Injury Severity Score was 29 (range, 2-75), and 31 (33%) of 94 died within 30
      days. Most patients [82/94 (87%)] received their first pRBC transfusion during
      transport or within one hour of arrival at the emergency department (ED). For the
      82 patients receiving a first pRBC transfusion within one hour of ED arrival,
      each 10-minute increase in time to transfusion increased the odds of death [OR,
      1.27 (95% CI, 1.01-1.62; p = 0.044)], controlling for TRISS. At 30 days, 29/82
      (35%) patients who received a pRBC transfusion within one hour of ED arrival, and
      2 (16%) of 12 patients who received delayed transfusion were deceased
      (difference, 19%; 95% CI, -5% to 42%). CONCLUSION: In this study, delays in time
      to pRBC administration of as short as 10 minutes were associated with increased
      odds of death for patients receiving ultra-early pRBC transfusion. Expedient
      prehospital and ED transfusion capabilities may improve outcomes after trauma.
      LEVEL OF EVIDENCE: Therapeutic/care management study, level III.

PMID- 27050885
TI  - Author's Reply to the Response to the Commentary of Naldi and Cazzaniga Entitled
      'Are All Screening Programmes Created Equal? The Case of Melanoma'.

PMID- 27050886
TI  - Agreement between two 3D ultrasound techniques for the assessment of the subpubic
      arch angle.
AB  - OBJECTIVES: To assess the reliability of a new three-dimensional (3D) ultrasound
      technique for the measurement of the subpubic arch angle (SPA) and the agreement
      between two contrast-enhancing 3D ultrasound techniques. METHODS: We acquired two
      static 3D transperineal volumes from 72 nulliparous women using two ultrasound
      machines equipped with two different 3D contrast enhancement and linear
      reconstruction softwares: 1. Oblique View Extended Imaging with HD-Volume Imaging
      (OVIX-HDVITM), Samsung; 2. Omniview with Volume Contrast Imaging (Omniview
      VCITM), GE Healthcare. An operator measured SPA once by OVIX-HDVI, and twice by
      Omniview-VCI, while another operator measured SPA once by Omniview-VCI. We
      evaluated intra- and inter-observer reproducibility of Omniview-VCI and
      intermethod agreement. Reproducibility and intermethod agreement were studied by
      means of intraclass correlation coefficient (ICC) and Bland-Altman method.
      RESULTS: Omniview-VCI SPA measurements showed excellent intraobserver and
      interobserver reproducibility (ICC 0.970; 95% C.I. 0.952 to 0.981, 0.932; 95%
      C.I. 0.893 to 0.957, respectively). Furthermore, Omniview VCI SPA measurements
      demonstrated excellent agreement with those performed by OVIX-HDVI technique (ICC
      0.943; 95 C.I. 0.911 to 0.964). No systematic difference was found in any of the
      reliability studies. CONCLUSIONS: OmniView-VCI is a reliable method for SPA
      assessment. Both OmniView-VCI and OVIX-HDVI can be used interchangeably for SPA
      measurement.

PMID- 27050887
TI  - A Case of Blunt Traumatic Cardiac Tamponade Successfully Treated by Out-of
      hospital Pericardial Drainage in a "Doctor-helicopter" Ambulance Staffed by
      Skilled Emergency Physicians.
AB  - We report a 55-year-old man who relapsed into a state of shock in an ambulance
      before arriving at our critical care center after a fall injury. The diagnosis of
      cardiac tamponade was made by portable ultrasound, and immediate
      pericardiocentesis and drainage were performed at the heliport. He was then
      transported immediately to our hospital with continuous drainage and surgery was
      performed. After surgery, the patient was transferred to the intensive care unit
      in stable condition. After undergoing rehabilitation, he made a full recovery and
      was discharged. This case illustrates that such patients can be treated reliably
      by pericardial drainage performed by skilled emergency physicians in the field by
      making use of the "doctor-helicopter" ambulance transportation system, followed
      by emergency surgery in a critical care center. 

PMID- 27050888
TI  - A Case of Superior Mesenteric Artery Occlusion Caused by Delayed Administration
      of Anticoagulants in a Patient with Nonvalvular Atrial Fibrillation.
AB  - A 86-year-old female with nonvalvular atrial fibrillation (NOVAF) who did not
      receive prophylactic anticoagulant treatment visited our hospital because of
      gastrointestinal symptoms. At first, acute gastroenteritis was suspected, but
      later she developed ileus and she was diagnosed with superior mesenteric artery
      occlusion (SMAO). We successfully performed the anesthetic management of this
      patient and subtotal resection of the small intestine was performed. Heparin was
      initiated after surgery, but she developed cerebral infarction later, and finally
      she died due to infection and anemia caused by melena. Although this patient was
      at high risk of thrombosis, she did not receive anticoagulant treatment. It might
      result in developing SMAO, and once SMAO occurred, thrombosis recurred even on
      anticoagulant treatment. This case suggested the importance of primary prevention
      of thrombosis in patients with NVAF.

PMID- 27050889
TI  - Clinical Characteristics of Legionella Pneumonia Diagnosed with Legionella
      Urinary Antigen Test.
AB  - OBJECTIVE: The aim of our study was to describe the clinical characteristics of
      Legionella pneumonia diagnosed with a positive urinary antigen test, and factors
      associated with severe Legionella pneumonia were investigated. METHODS: We
      retrospectively investigated the clinical characteristics of patients with
      Legionella pneumonia diagnosed at Tokai University Hospital between February 2006
      and June 2012. The clinical characteristics of ICU cases and non-ICU cases were
      compared. RESULTS: Twenty-six patients with Legionella pneumonia were identified
      (mean age 66.7 +/- 19.3). Twenty patients were men (76.9 %). Impaired
      consciousness was observed in 12 patients (46.2 %), followed by gastrointestinal
      symptoms (38.5 %). Ten patients had severe pneumonia which required ICU
      admission. A case-controlled study comparing non-ICU cases and ICU cases
      demonstrated that cases with diabetes (OR 10.1, 95 % CI 1.1-90.5) and tachycardia
      (OR 10.1, 95 % CI 1.1-90.5) were significantly associated with ICU admission.
      CONCLUSIONS: Legionella pneumonia did not always present as severe pneumonia.
      Extrapulmonary manifestations may be useful clues for diagnosis. Diabetic
      patients have not only a risk of contracting Legionella pneumonia, but also a
      risk of progression. Legionella pneumonia should be included in the differential
      diagnosis even in cases of mild to moderate pneumonia when presenting with
      extrapulmonary symptoms, especially in diabetic patients.

PMID- 27050890
TI  - Ameliorative Effects of Kolaviron, a Biflavonoid Fraction from Garcinia Kola
      Seed, on Hepato-renal Toxicity of Anti-tuberculosis Drugs in Wistar Rats.
AB  - BACKGROUND: Tuberculosis (TB) is an infectious disease of international health
      priority. The combination of anti-TB drugs (4-Tabs)- isoniazid (INH), rifampicin
      (RIF), pyrazinamide (PZA) and ethambutol (ETB) are effective in the management of
      the disease, however, their toxic effect is a major concern. PURPOSE: The study
      was designed to evaluate the toxicity of anti-TB drugs in male Wistar rats and
      possible ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola
      seeds. METHODS: Twenty-eight rats were assigned into four groups; Group 1
      (Control) received corn oil, Group 2 (4-Tabs) received therapeutic doses of INH
      (5 mg/kg), RIF (10 mg/kg), PZA (15 mg/kg) and ETB (15 mg/kg) in combination,
      Group 3 (4-Tabs + KV) received INH, RIF, PZA, ETB and KV (200 mg/kg) and Group 4
      (KV) received KV (200 mg/kg) by oral gavage three times per week for 8
      consecutive weeks. RESULTS: Administration of 4-Tabs caused oxidative stress
      resulting in significant (p = 0.031, 0.027) increase in malondialdehyde levels in
      the liver and kidney of rats by 101% and 34%, respectively. Also, 4-Tabs caused
      significant (p = 0.023-0.035) elevation of serum alanine and aspartate
      aminotransferases by 41% and 48%, creatinine by 252% and total bilirubin by 89%,
      respectively. In contrast, hepatic and renal antioxidant indices- reduced
      glutathione, glutathione peroxidase, glutathione-s-transferase and superoxide
      dismutase were significantly (p = 0.028-0.039) decreased in 4-Tabs-treated rats.
      Co-administration of KV with 4-Tabs significantly restored the antioxidant
      parameters and biochemical indices to near normal. CONCLUSION: These findings
      suggest that anti-TB drugs elicit oxidative damage in liver and kidney of rats
      while KV protects against the adverse effects via antioxidative mechanism.

PMID- 27050891
TI  - Colonic High-grade Tubular Adenomas Associated with Schistosoma japonicum.
AB  - We reported a case of sigmoid colonic high grade tubular adenomas associated with
      deposited ova of Schistosoma japonicum. A 76-year-old Japanese man was referred
      to our colonoscopy due to a positive fecal occult blood test. He had a medical
      history of schistosomiasis japonica. The colonoscopy revealed that there were two
      sigmoid colon polyps, approximately 8 mm in diameter. These were removed by
      endoscopic mucosal resection (EMR). Pathological examination revealed high grade
      tubular adenomas and deposited some ova of Schistosoma japonicum with severe
      fibrotic change and granuloma formation in the submucosal layer. Colonic
      schistosomiasis is a probable independent risk factor for the development of
      colorectal carcinogenesis. 

PMID- 27050892
TI  - Preparation of Clinically Useful Sennoside-reduced Rhubarb.
AB  - OBJECTIVE: The aim of this study was to develop a method of removing sennoside to
      reduce the cathartic effect of rhubarb while conserving its other pharmacological
      activities. METHODS: Rhubarb powder was steam autoclaved at 121 degrees C and
      0.14 MPa for 20, 60, or 120 minutes, and HPLC analysis was conducted to determine
      levels of rhubarb components. Mice were fed non-autoclaved or 20-minute
      autoclaved rhubarb extracts. Feces were collected and weighed over a 24-hour
      period. India ink was orally administered to determine the distance of fecal
      migration through the intestinal tract. RESULTS: Autoclaving 20, 60, and 120
      minutes decreased sennoside A and B to trace levels but only autoclaving 20
      minutes conserved most of the (+)-catechin, (-)-epicatechin, and (-)-epicatechin
      gallate contents (i.e., 69%, 90%, 88%, respectively). Therefore only rhubarb
      autoclaved for 20 minutes was used in subsequent experiments. Fecal output (in g)
      in mice treated with water (control), autoclaved rhubarb, and non-autoclaved
      rhubarb was 2.78 +/- 0.07, 3.30 +/- 0.13 (p = 0.348), and 3.81 +/- 0.07 (p =
      0.005). India ink migration was far less in mice treated with autoclaved rhubarb
      vs non-autoclaved rhubarb. CONCLUSION: Steam autoclaving the rhubarb for 20
      minutes reduces sennoside levels and its cathartic activity while conserving its
      other pharmacological activities.

PMID- 27050893
TI  - A Surgical Case of Primary Splenic Malignant Lymphoma Complicating Chronic
      Hepatitis C.
AB  - The patient was a 70-year-old man. Hepatic dysfunction was found in 1988 and
      chronic hepatitis C was diagnosed in 1993. He received interferon-alpha therapy,
      but did not respond to it. Thereafter, he was treated with ursodeoxycholic acid.
      In September 2010, abdominal ultrasound showed a hypoechoic tumor (29 * 25 mm) in
      the lower pole of the spleen, and this lesion became larger one year later (74 *
      66 * 71 mm). Abdominal CT revealed a hypovascular heterogeneous tumor with smooth
      margins on both dynamic and delayed phase scans. MRI displayed a tumor with a low
      signal intensity on T2WI. Abdominal angiography confirmed that the lesion was
      hypovascular. 67Ga scintigraphy showed abnormal accumulation confined to the
      spleen. Bone marrow biopsy did not reveal any abnormalities. Based on these
      findings, primary splenic malignant lymphoma (PSML) complicating chronic
      hepatitis C was diagnosed and splenectomy was performed. A tumor (78 * 60 mm) was
      found in the lower pole of the resected spleen and pathologic examination
      revealed diffuse large B cell lymphoma (DLBCL). Four courses of postoperative R
      CHOP therapy were performed. At present, he continues to use ursodeoxycholic acid
      with no recurrence after four years. In conclusion, we report our experience of a
      patient who had PSML complicating chronic hepatitis C with discussion of the
      literature. 

PMID- 27050894
TI  - A Rare Case of Subclinical Primary Aldosteronism and Subclinical Cushing's
      Syndrome without Cardiovascular Complications.
AB  - We report a rare case of subclinical primary aldosteronism (PA) and subclinical
      Cushing's syndrome (CS). A 49-year-old woman was referred to our hospital for the
      evaluation of an adrenal incidentaloma. The patient had no previous medical
      history and no family history of notable illness. Her blood pressure was 103/60
      mmHg. She had no Cushingoid features. Routine laboratory examinations were within
      the normal ranges including normokalemia. Based on the endocrinological results
      and imaging findings, we finally made a diagnosis of subclinical PA caused by
      both adrenal glands and subclinical CS caused by bilateral adrenal tumors.
      Interestingly, this patient had no risk factors for cardiovascular disease. In
      addition, the optimal management of patients with subclinical CS and subclinical
      PA has not been established. Therefore, we are observing her without medical
      therapy. Four years after diagnosis, no cardiovascular complications have been
      detected, including cerebral infarction, chronic kidney disease, cardiomegaly on
      echocardiography, and atherosclerosis on carotid ultrasonography. One important
      question is why the excessive hormone secretion did not affect the cardiovascular
      status of this patient. In this regard, we discuss several possible mechanisms
      including mineralocorticoid resistance and glucocorticoid sensitivity. 

PMID- 27050895
TI  - Aggressive Angiomyxoma of the Vulva with No Recurrence on a 5-year Follow up: A
      Case Report.
AB  - We report a case of vulvar aggressive angiomyxoma (AA) which is a rare, slow
      growing and benign tumor of mesenchymal origin, but has a high risk of local
      recurrence. A 49-year-old Japanese female was referred to us with a large mass of
      the left vulva, measuring 15*9.5*9 centimeters. She underwent surgical excision
      of the tumor with no evidence of recurrence on a 5-year follow up. In this case,
      histopathological examination and immunohistochemical staining after excision
      revealed a diagnosis of vulvar AA with estrogen and progesterone receptors
      positive. Aggressive angiomyxoma of the vulva needs to be distinguished from
      benign myxoid tumor with a low risk of local recurrence as well as from malignant
      neoplasma. The first line treatment of AA is complete surgical excision with
      tumor free margins, it will reduce the recurrence. 

PMID- 27050896
TI  - Preparation of Bioadhesive Phosphorescent Particles and Their Use as Markers for
      Video-oculography of Mice.
AB  - OBJECTIVE: To develop a bioadhesive phosphorescent particle that can be used as a
      marker in video-oculography to assess eye movements in the dark without drug
      treatment. METHODS: The marker was prepared by spray-coating a Sr4Al14O25: Eu2+,
      Dy3+ phosphor with a carboxyvinyl polymer. The morphologic, luminescent and
      adhesive properties were assessed. The dynamic properties of VOR measured by the
      marker were compared with those obtained by tracking the pupil under miotic
      treatment. RESULTS: Non-aggregated and non-fused particles having diameters of
      about 5um could be prepared by polymeric coating of the phosphor, resulting in
      particles small enough not to restrict eye movement. Although the phosphorescent
      of the particles decreased with increasing thickness of the coating layer, the
      coated particles were detectable in the dark for at least 60 min. The thicker the
      coating layer was, the higher the adhesiveness of the particles obtained. The
      particles having the thickest coating layer were retained on the corneal surface
      during VOR measurement and thus performed well as a marker in video-oculography.
      The dynamic properties of VOR measured by the marker were essentially identical
      to those obtained by tracking the pupil under miotic treatment. CONCLUSION: Our
      marker will contribute to understanding the mechanisms underlying motor learning.

PMID- 27050897
TI  - Autism Spectrum Disorder and Chiari 1 Malformation Co-occurring in a Child.
AB  - Very few studies have shown associations between autism spectrum disorder,
      attention deficit hyperactivity disorder and Chiari 1 malformation. Here, we
      report an 10-year-old male that presented after having seizures with a history of
      Chiari 1 malformation, autism spectrum disorder and ADHD with moderate mental
      retardation and speech delay. This case highlights the fact that autism spectrum
      disorder as biologically based neurodevelopmental disorder with altered brain
      growth may be associated with Chiari 1 malformation and ADHD. 

PMID- 27050898
TI  - A Case Report of an Incidentally Diagnosed Blind-ending Bifid Ureter in a Patient
      with Ovarian Cancer.
AB  - A 58-year-old Japanese female was admitted to our hospital for treatment of
      ovarian cancer. She had no urinary tract symptoms at the time of presentation.
      Preoperative CT (Computed Tomography) was performed for surgical planning, and it
      revealed two left-sided ureters including a short ureter with a blind, cystic
      ending and a short ureter joined to the main ureter before entering into the
      bladder. On CT urography, these radiological findings were compatible with a
      blind-ending bifid ureter. Preoperatively, a double J stent was inserted into the
      normal left ureter, and then the blind-ending bifid ureter was resected before an
      ovarian cancer operation. 

PMID- 27050899
TI  - Nicorandil Inhibits Cyclic Strain-Induced Interleukin-8 Expression in Human
      Umbilical Vein Endothelial Cells.
AB  - BACKGROUND: Nicorandil, a mitochondrial adenosine triphosphate-sensitive
      potassium (mitoKATP) channel opener, exerts protective effects on the
      cardiovascular system. This study examined the effect of nicorandil on cyclic
      strain-induced interleukin-8 (IL-8) expression in human umbilical vein
      endothelial cells (HUVECs). METHODS: Cultured HUVECs were exposed to cyclic
      strain in the presence or absence of nicorandil (1-10 MUmol/l); we then analyzed
      IL-8 expression. We also assessed the effects of nicorandil on heme oxygenase-1
      (HO-1) expression and cyclic strain-modulated IL-8 expression after HO-1
      silencing in HUVECs. SUMMARY: HUVECs exposed to cyclic strain showed increased IL
      8 messenger RNA expression and protein secretion. Nicorandil (1-10 MUmol/l)
      inhibited cyclic strain-induced IL-8 expression, whereas 5-hydroxydecanoate (100
      MUmol/l), a selective inhibitor of the mitoKATP channel, completely reversed the
      inhibitory effects of nicorandil on cyclic strain-induced IL-8 expression. We
      demonstrated that nicorandil increased HO-1 expression in HUVECs. In addition,
      cobalt protoporphyrin (10 MUmol/l), an inducer of HO-1 expression, mimicked the
      effects of nicorandil and inhibited IL-8 expression under cyclic strain, whereas
      zinc protoporphyrin IX (10 MUmol/l), an inhibitor of HO-1 expression, antagonized
      the effect of nicorandil. HO-1 silencing significantly abrogated the inhibitory
      effects of nicorandil on cyclic strain-induced IL-8 expression, suggesting that
      HO-1 plays a role in the mechanism of action of nicorandil. KEY MESSAGES: This
      study is the first to report that nicorandil inhibits cyclic strain-induced IL-8
      expression through the induction of HO-1 expression in HUVECs. This finding
      provides valuable new insight into the molecular pathways contributing to the
      vasoprotective effects of nicorandil.

PMID- 27050900
TI  - Bilateral neck fistulas.

PMID- 27050901
TI  - Personalized nutrition by prediction of glycaemic responses: fact or fantasy?

PMID- 27050902
TI  - A longitudinal study of systemic inflammation and recovery of lean body mass
      among malnourished HIV-infected adults starting antiretroviral therapy in
      Tanzania and Zambia.

PMID- 27050903
TI  - Controlled electropolymerisation of a carbazole-functionalised iron porphyrin
      electrocatalyst for CO2 reduction.
AB  - Using a one-step electropolymerisation procedure, CO2 absorbing microporous
      carbazole-functionalised films of iron porphyrins are prepared in a controlled
      manner. The electrocatalytic reduction of CO2 for these films is investigated to
      elucidate their efficiency and the origin of their ultimate degradation. 

PMID- 27050904
TI  - Illness du Jour.

PMID- 27050905
TI  - Senecio changii (Asteraceae: Senecioneae), a New Species from Sichuan, China.
AB  - Senecio changii (Asteraceae: Senecioneae), a new species from Muli, Sichuan,
      southwestern China, is described. It is distinguished in Chinese Senecio s.s. by
      having lyrate-pinnatisect to pinnatisect leaves and a single terminal large
      discoid capitulum which is somewhat nodding. Evidence from floral
      micromorphology, karyology and molecular phylogenetic analyses based on the
      nuclear ITS/ETS sequence data all support its membership within Senecio s.s. 

PMID- 27050906
TI  - mTOR transcriptionally and post-transcriptionally regulates Npm1 gene expression
      to contribute to enhanced proliferation in cells with Pten inactivation.
AB  - The mammalian target of rapamycin (mTOR) plays essential roles in the regulation
      of growth-related processes such as protein synthesis, cell sizing and metabolism
      in both normal and pathological growing conditions. These functions of mTOR are
      thought to be largely a consequence of its cytoplasmic activity in regulating
      translation rate, but accumulating data highlight supplementary role(s) for this
      serine/threonine kinase within the nucleus. Indeed, the nuclear activities of
      mTOR are currently associated with the control of protein biosynthetic capacity
      through its ability to regulate the expression of gene products involved in the
      control of ribosomal biogenesis and proliferation. Using primary murine embryo
      fibroblasts (MEFs), we observed that cells with overactive mTOR signaling
      displayed higher abundance for the growth-associated Npm1 protein, in what
      represents a novel mechanism of Npm1 gene regulation. We show that Npm1 gene
      expression is dependent on mTOR as demonstrated by treatment of wild-type and
      Pten inactivated MEFs cultured with rapamycin or by transient transfections of
      small interfering RNA directed against mTOR. In accordance, the mTOR kinase
      localizes to the Npm1 promoter gene in vivo and it enhances the activity of a
      human NPM1-luciferase reporter gene providing an opportunity for direct control.
      Interestingly, rapamycin did not dislodge mTOR from the Npm1 promoter but rather
      strongly destabilized the Npm1 transcript by increasing its turnover. Using a
      prostate-specific Pten-deleted mouse model of cancer, Npm1 mRNA levels were found
      up-regulated and sensitive to rapamycin. Finally, we also showed that Npm1 is
      required to promote mTOR-dependent cell proliferation. We therefore proposed a
      model whereby mTOR is closely involved in the transcriptional and
      posttranscriptional regulation of Npm1 gene expression with implications in
      development and diseases including cancer.

PMID- 27050907
TI  - Fatal liver cyst rupture in polycystic liver disease complicated with autosomal
      dominant polycystic kidney disease: A case report.
AB  - A 59-year-old man was struck in the abdomen and later presented to the emergency
      room. His blood pressure dropped and eventually died 16h post trauma and just
      before emergency exploratory laparotomy. Autopsy revealed two polycystic kidneys
      and a giant polycystic liver with two ruptures. Blood (2225g) was observed in the
      peritoneum and the body-surface injury was minor. Genetic testing was performed
      to confirm that the man had an autosomal dominant polycystic kidney disease
      (ADPKD) complicated by polycystic liver disease (PLD). Autopsy, histopathology
      and medical history showed that the cause of death was the ruptures of liver
      cysts due to trauma. In this communication, we describe a fatal case and hope to
      increase awareness and recognition of PLD and ADPKD. We also wish to indicate
      that due to the fragile condition of liver cysts, trauma should be considered
      even if the body-surface injury is minor in fatal cases of PLD patient with a
      traumatic history. 

PMID- 27050908
TI  - Mud-bath therapy and oral glucosamine sulfate in patients with knee
      osteoarthritis: a randomized, controlled, crossover study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of combined treatment of mud-bath
      therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee
      osteoarthritis (OA). METHODS: This study was a randomised, controlled, crossover
      investigation. Patients were randomly assigned (1:1) by the investigators to two
      groups, named group 1 and 2. Group 1 included twenty-three patients receiving
      oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd
      month of treatment (T3) and a combined treatment of both mud-bath therapy and
      GlcN-S from T3 to the end of the study at six months (T6). Group 2 included
      twenty-two patients receiving a combined treatment of both mud-bath therapy and
      GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S
      treatment alone, from T3 to T6. Primary endpoints of the study consisted of
      evaluating OA severity and activity at baseline and at follow-up visits. RESULTS:
      All 45 patients, eligible for the study, completed the period of the crossover.
      In group 1, no significant difference was shown in the comparison from T0 to T3,
      while from T3 to T6 most variables were significantly improved. In group 2,
      instead, the comparison between T0 and T3 showed a significant difference in
      different parameters. When comparing T3 and T6, despite an improvement of all the
      variables, no significant difference was shown. CONCLUSIONS: The association of
      GlcN-S and mud-bath therapy has a positive and safe role in improving pain,
      function and quality of life in knee OA patients.

PMID- 27050909
TI  - Repetitive nonreentrant ventriculoatrial synchrony: An underrecognized cause of
      pacemaker-related arrhythmia.
AB  - Similar to endless loop tachycardia (ELT), repetitive nonreentrant
      ventriculoatrial synchrony (RNRVAS) is a ventriculoatrial (VA) synchrony
      pacemaker-mediated arrhythmia. RNRVAS was first described in 1990 and can only
      occur in the presence of retrograde VA conduction and dual-chamber or cardiac
      resynchronization devices with tracking (P-synchronous ventricular pacing such as
      DDD, DDDR) or nontracking pacing modes that allow AV-sequential pacing (DDI,
      DDIR). RNRVAS is promoted by (1) high lower rate limit or any feature that allows
      rapid pacing, (2) long AV intervals, or (3) long postventricular atrial
      refractory period (PVARP). In contrast to ELT, RNRVAS is a less well-recognized
      form of pacemaker-mediated arrhythmia; thus, unlike ELT, there are no specific
      device algorithms to prevent, recognize, and terminate RNRVAS. However, RNRVAS
      has been recently shown to occur frequently. We present a series of cases, some
      of which were found fortuitously. Owing to its clinical implications, we propose
      that algorithms should be developed to prevent, identify, and terminate RNRVAS.

PMID- 27050910
TI  - Catheter ablation of ventricular tachycardia: Lessons learned from past clinical
      trials and implications for future clinical trials.
AB  - Catheter ablation of ventricular tachycardia (VT) has evolved in recent years,
      especially in patients with ischemic heart disease. Data from prospective studies
      show that VT catheter ablation reduces the risk of recurrent VT; however, there
      is a paucity of data on the effect of VT catheter ablation on mortality and
      patient-centered outcomes such as quality of life. Performing randomized clinical
      trials of VT catheter ablation can be fraught with challenges, and, as a result,
      several prior trials of VT catheter ablation had to be stopped prematurely. The
      main challenges are inability to blind the patient to therapy to obtain a
      traditional control group, high crossover rates between the 2 arms of the study,
      patient refusal to participate in trials in which they have an equal chance of
      receiving a "pill" vs an invasive procedure, heterogeneity of mapping and
      ablation techniques as well as catheters and equipment, rapid evolution of
      technology that may make findings of any long trial less relevant to clinical
      practice, lack of consensus on what constitutes acute procedural and long-term
      success, and presentation of patients to electrophysiologists late in the course
      of their disease. In this article, a panel of experts on VT catheter ablation
      and/or clinical trials of VT catheter ablation review challenges faced in
      conducting prior trials of VT catheter ablation and offer potential solutions for
      those challenges. It is hoped that the proposed solutions will enhance the
      feasibility of randomized clinical trials of VT catheter ablation.

PMID- 27050911
TI  - Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?
AB  - AIMS: Baseline HbA1c is a major predictor of response to glucose lowering therapy
      and therefore a potential confounder in studies aiming to identify other
      predictors. However, baseline adjustment may introduce error if the association
      between baseline HbA1c and response is substantially due to measurement error and
      regression to the mean. We aimed to determine whether studies of predictors of
      response should adjust for baseline HbA1c. METHODS: We assessed the relationship
      between baseline HbA1c and glycaemic response in 257 participants treated with
      GLP-1R agonists and assessed whether it reflected measurement error and
      regression to the mean using duplicate 'pre-baseline' HbA1c measurements not
      included in the response variable. In this cohort and an additional 2659
      participants treated with sulfonylureas we assessed the relationship between
      covariates associated with baseline HbA1c and treatment response with and without
      baseline adjustment, and with a bias correction using pre-baseline HbA1c to
      adjust for the effects of error in baseline HbA1c. RESULTS: Baseline HbA1c was a
      major predictor of response (R2 = 0.19,beta = -0.44,p<0.001).The association
      between pre-baseline and response was similar suggesting the greater response at
      higher baseline HbA1cs is not mainly due to measurement error and subsequent
      regression to the mean. In unadjusted analysis in both cohorts, factors
      associated with baseline HbA1c were associated with response, however these
      associations were weak or absent after adjustment for baseline HbA1c. Bias
      correction did not substantially alter associations. CONCLUSIONS: Adjustment for
      the baseline HbA1c measurement is a simple and effective way to reduce bias in
      studies of predictors of response to glucose lowering therapy.

PMID- 27050912
TI  - Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone
      therapy.
AB  - We report a case of an intracranial germ cell tumor (iGCT) that showed rapid
      enlargement after human chorionic gonadotropin (hCG) hormone therapy for
      pituitary hypogonadism. A 16-year-old boy presented with headache and was
      diagnosed with a suprasellar tumor. He was initially observed without surgery.
      Intranasal desmopressin therapy was started for central diabetes insipidus, but
      there was no change in the tumor size on MRI. The diagnosis of the tumor remained
      unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating
      and luteinizing hormone) and testosterone progressively decreased, and the
      patient developed pituitary hypogonadism and complained about his undeveloped
      beard, lack of underarm hair, and erectile dysfunction. Intramuscular
      gonadotropin injection (hCG 5000U*2/week) was started at age 20. Eight months
      after the first gonadotropin injection, the MRI showed tumor growth with vivid
      enhancement. Craniotomy was performed and the tumor was partially resected. The
      histological diagnosis was immature teratoma. After surgery, the patient was
      treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also
      received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to
      the residual tumor, after which the tumor decreased in size. We postulate that
      iGCT may be at risk of progression during hCG hormone therapy. Thus, careful
      monitoring is required for a patient with iGCT who receives this therapy. 

PMID- 27050913
TI  - Revision surgeries following vagus nerve stimulator implantation.
AB  - The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly,
      treatment for intractable epilepsy. We aimed to analyze the incidence, timing,
      and clinical/demographic associations of revision surgery post-VNS implantation
      in epilepsy patients. The Thomson Reuters MarketScan database, containing data
      from 23-50million individuals, was used. Epilepsy patients receiving VNS
      implantations from 2003 to 2009 were identified by Current Procedural Terminology
      and International Classification Of Diseases Ninth Revision codes. Incidence and
      timing of subsequent implant-related surgeries were recorded. Events were
      described using time-to-event methodology, with Kaplan-Meier failure
      estimation/Cox proportional hazard models adjusted for clinical/demographic
      factors. In 1234 patients, average incidence of revision surgeries over 6years of
      follow-up were <1%, <3%, 4-10%, and <1% for VNS electrode revision, battery
      revision/removal, battery replacement/implantation, and infection washout,
      respectively. For electrode revision and battery revision/replacement, the
      incidence was higher in the first year and for battery replacement in later
      years. Age, sex, insurance type, or geographic region did not significantly
      impact event occurrence. Implant-related revision surgeries are rare. Some events
      occur more often in certain follow-up years than others; none are significantly
      impacted by age, sex, insurance type, or geographic region. The most common
      reason for revision was battery replacement several years after VNS placement. 

PMID- 27050914
TI  - Invasive central nervous system aspergillosis in a patient with Crohn's disease
      after treatment with infliximab and corticosteroids.
AB  - Aspergillus species are emerging as a significant cause of pneumonia mortality in
      immune compromised hosts, with haematological spread being a rare and life
      threatening complication. The central nervous system (CNS) as a site for
      extrapulmonary spread is rarer still. We report a case of CNS disseminated
      aspergillosis in a patient treated with corticosteroids and infliximab, an
      immunomodulatory agent commonly used in the treatment of inflammatory bowel
      disease, and review the available literature regarding this rare pathology. 

PMID- 27050915
TI  - p38MAPK activation and DUSP10 expression in meningiomas.
AB  - The mitogen activated protein kinase (MAPK) p38MAPK has been implicated in
      regulation of cell proliferation and apoptosis. However, expression, activation
      and regulation has not been studied in meningiomas, to our knowledge. p38MAPK is
      regulated, in part, by dual specificity phosphatases (DUSP) that inactivate
      signaling by dephosphorylation. DUSP10 is also a likely participant in regulating
      meningioma proliferation. Five fetal and an adult human leptomeninges and 37
      meningioma cultures (MC) were evaluated for DUSP10 as well as phosphorylation of
      its substrates p38MAPK and p44/42MAPK by western blot and DUSP10 expression by
      polymerase chain reaction. Platelet derived growth factor-BB (PDGF-BB),
      transforming growth factor B1 (TGFB1) and cerebrospinal fluid effects on DUSP10
      and signaling were also studied in vitro. DUSP10 and phospho-p38MAPK and phospho
      p44/42MAPK were detected in all six leptomeninges. DUSP10 was detected in 13 of
      17 World Health Organization grade I, 11 of 14 grade II and four of six grade III
      meningiomas. Phospho-p38MAPK was detected in nine of 17 grade I, two of six grade
      II, and four of six grade III meningiomas. In the majority of meningiomas DUSP10
      expression correlated inversely with phosphorylation of p38MAPK. PDGF-BB
      increased DUSP10 in MC2 and MC4 and weakly in MC3. TGFB1 increased
      phosphorylation of p38MAPK and caspase 3 activation. Thus p38MAPK and DUSP10
      likely participate in the pathogenesis of meningiomas. 

PMID- 27050916
TI  - Treatment of patients with mild acute ischemic stroke and associated large vessel
      occlusion.
AB  - Several recent studies have shown that patients presenting with mild acute
      ischemic stroke (mAIS) symptoms may have an unfavorable natural history. The
      presence of associated large vessel occlusion (LVO) may lead to even worse
      outcomes, but most mAIS patients are still excluded from acute stroke treatment
      (AST). A retrospective review of patients with acute ischemic stroke presenting
      to our institution between 2010 and 2014 was carried out. Inclusion criteria were
      mAIS (initial National Institutes of Health Stroke Scale [NIHSS] ?7) due to LVO,
      presenting within 6hours from onset. Demographics, treatments and short-term
      outcomes were analyzed. Favorable 30day outcome was defined as modified Rankin
      Scale (mRS) ?2. Out of 2636 patients, 62 patients (median age 63years, 33 (53.2%)
      males) met inclusion criteria. The anterior circulation was involved in 74.1%.
      Median admission NIHSS and pre-admission mRS were 4 and 0, respectively. Twenty
      three patients (71.8%) received AST (intravenous tissue plasminogen activator:
      14, intra-arterial therapy: 4, both: 5). Favorable outcomes were 4.5 times higher
      in treated (78.3%) versus untreated (53.8%) patients (odds ratio 4.5, 95%
      confidence interval 1.26-19.2; p=0.028). None of the treated patients had
      symptomatic intracranial hemorrhage. We demonstrate that a significant proportion
      of untreated mAIS patients with LVO have an unfavorable natural history. Our
      results suggest better outcomes in patients who receive early therapy rather than
      conservative management. The detection of LVO, even with mild clinical symptoms,
      may prompt rapid treatment considerations. 

PMID- 27050917
TI  - Dynamic evolution of D-dimer level in cerebrospinal fluid predicts poor outcome
      in patients with spontaneous intracerebral hemorrhage combined with
      intraventricular hemorrhage.
AB  - The risk of mortality in patients with intracerebral hemorrhage (ICH)
      significantly increases when complicated by intraventricular hemorrhage (IVH). We
      hypothesize that serial measurement of cerebrospinal fluid (CSF) D-dimer levels
      in patients with both ICH and IVH may serve as an early marker of IVH severity.
      We performed a prospective study of 43 consecutive ICH patients combined with IVH
      and external ventricular drainage placement admitted in our institution from 2005
      2006. IVH severity (Graeb score) and fibrinolytic activity were evaluated
      continuously for 7days using CT scans and CSF D-dimer levels. The primary outcome
      was 30day mortality. Overall 30day mortality was 26% (n=11), with eight deaths
      (72.7%) after 3days (D3). Graeb score and CSF D-dimer on admission (D0) were not
      significantly different between survivors and non-survivors. The temporal
      profiles of both parameters were distinctly different, with a downward trend in
      survivors and an upward trend in non-survivors. A mortality rate of 54% was
      observed between D0-D3 when both scores increased during this interval. In
      contrast, the mortality was only 4% when both measures decreased during this
      interval. Early phase (D0-D3) CSF D-dimer or Graeb score change demonstrated high
      sensitivity of 88% and specificity of 81% when predicting 30day mortality. Early
      phase CSF D-dimer change in patients with both ICH and IVH is accurate in
      predicting mortality and may be utilized as a cost-effective surrogate indicator
      of IVH severity. Serial monitoring of CSF D-dimer dynamic changes is useful for
      early identification of patients with hematoma progression and poor outcome. 

PMID- 27050918
TI  - Histological analysis of surgical samples and a proposed scoring system for
      infections in intervertebral discs.
AB  - Back pain remains one the most prevalent types of pain and disability worldwide.
      Infection is estimated to be the underlying cause in approximately 0.01% of
      patients. Despite recent evidence demonstrating prominent infection rates, a
      standardised algorithm for diagnosis of disc infection is lacking.
      Histopathological evaluation can aid in confirming inflammatory changes and also
      in identifying degenerative changes. Hence, standardising practice through a
      clear scoring system with regards to inflammation and degeneration may have some
      utility in the clinical setting. To our knowledge no such systems exist
      specifically for intervertebral disc infection. A literature review of current
      methods of scoring inflammation and degeneration in spine surgery and orthopaedic
      surgery was performed. Based on the current evidence, a scoring system for disc
      inflammatory and degenerative changes was proposed. We propose four domains for
      consideration: (1) granulation tissue, (2) dense fibrosis, (3) chronic
      inflammatory cells, and (4) neutrophil count. The non-standardised nature of
      diagnosing infections and degeneration in the spinal surgery literature means
      that this scoring system is currently of particular value. Based on a literature
      review, our proposed method for diagnosis incorporates a combination of
      histopathological criteria expected to increase diagnostic sensitivity in the
      setting of disc infection. Overall, scoring can be applied to surgically obtained
      material and integrated directly into routine pathological practice. 

PMID- 27050919
TI  - Ectopic intracranial germinoma.
AB  - Intracranial ectopic germinomas are often associated with synchronous midline
      disease. Germinomas involving the corpus callosum are exceedingly rare. The
      reported imaging appearance is not as varied as one might expect and a review of
      the literature reveals a few common imaging features amongst most ectopic
      lesions, including cyst formation. We report a 24-year-old man with
      panhypopituitarism. Neuroimaging revealed three enhancing lesions involving the
      pituitary infundibulum, the pineal region, and a parenchymal lesion involving the
      genu of the corpus callosum. The described ectopic mass, a parenchymal lesion,
      was associated with small peripheral cysts. Stereotactic biopsy and
      histopathological evaluation revealed this mass to be a germinoma. Following
      chemotherapy and radiation therapy, there was near-total resolution of the
      intracranial disease. Preoperative imaging plays an important role, not only in
      delineating the extent of disease, but also in assisting in generating an
      appropriate differential diagnosis. Germinomas in the corpus callosum are
      exceedingly rare but should be considered in the differential of any young
      patient with a characteristic cystic and solid intra-axial mass. 

PMID- 27050920
TI  - Comment on the case report entitled "Secondary orthostatic tremor in the setting
      of cerebellar degeneration".

PMID- 27050921
TI  - Recurrence of chest wall hydatid cyst disease involving the thoracic spine in an
      Australian patient.
AB  - Hydatid disease involving the spine is a relatively uncommon occurrence. The
      cestode Echinococcus granulosus is the primary pathogen associated with hydatid
      disease and most patients present with signs and symptoms of spinal cord
      compression depending on the location of the spinal involvement. We present a
      rare case of recurrent hydatid disease with extensive hemithorax involvement,
      including the thoracic spine, associated with spinal cord compression. This case
      highlights the role of staged and minimally invasive spine surgery in spinal
      hydatid disease with spinal cord compression, the importance of ongoing medical
      treatment and long term follow-up. 

PMID- 27050922
TI  - Insights into the adaptive response of the plant-pathogenic oomycete Phytophthora
      capsici to the fungicide flumorph.
AB  - Phytophthora capsici is an important oomycete plant pathogen that causes
      significant losses worldwide. The carboxylic acid amide fungicide flumorph has
      shown excellent activity against oomycete plant pathogens. Despite its potential,
      there remains concern that the sexual reproduction of oomycete pathogens, which
      results in genetic recombination, could result in the rapid development of
      resistance to flumorph. The current study utilized an iTRAQ (isobaric tags for
      relative and absolute quantitation) based method to compare differences between
      the proteome of the parental P. capsici isolate PCAS1 and its sexual progeny S2
      838, which exhibits significant resistance to flumorph. A total of 2396
      individual proteins were identified, of these, 181 were considered to be
      associated with the adaptive response of P. capsici to flumorph. The subsequent
      bioinformatic analysis revealed that the adaptive response of P. capsici to
      flumorph was complex and regulated by multiple mechanisms, including utilising
      carbohydrate from the host environment to compensate for the cell wall stress
      induced by flumorph, a shift in energy generation, decreased amino acids
      biosynthesis, and elevated levels of proteins associated with the pathogen's
      response to stimulus and transmembrane transport. Moreover, the results of the
      study provided crucial data that could provide the basis for early monitoring of
      flumorph resistance in field populations of P. capsici. 

PMID- 27050923
TI  - Systematic Approach for the Construction of Niobium and Tantalum Sulfide
      Clusters.
AB  - Treatment of the imido complexes [MCl3(NR)py2] (R = (t)Bu, 2,6-Me2C6H3; M = Nb 1,
      3; Ta 2, 4) (Xyl = 2,6-Me2C6H3) with (Me3Si)2S in a 1:1 ratio afforded the new
      cube-type sulfide clusters [MCl(NR)py(MU3-S)]4 (R = (t)Bu, 2,6-Me2C6H3; M = Nb 5,
      7; Ta 6, 8) with loss of Me3SiCl. Reactions of 5 and 6 with
      cyclopentadienyllithium in 1:4 ratio resulted in the rupture of the coordinative
      M-S bonds and the replacement of a pyridine molecule and a chlorine atom by an
      eta(5)-cyclopentadienyl group in each metal center, affording the compounds
      [M(eta(5)-C5H5)(N(t)Bu)(MU-S)]4 (M = Nb 9, Ta 10). These processes may develop
      through formation of the complexes [M4(eta(5)-C5H5)2(MU-Cl)(N(t)Bu)4py2(MU3
      S)2(MU-S)2](C5H5) (M = Nb 11, Ta 12), also obtained by reaction of 5 and 6 with
      cyclopentadienyllithium in 1:3 ratio. As further evidence, 11 and 12 led to
      complexes 9 and 10 by treatment with one more equivalent of the lithium reagent.
      The structural study of these metal sulfide clusters has been also performed by X
      ray crystallography. 

PMID- 27050924
TI  - Red Hair, Light Skin, and UV-Independent Risk for Melanoma Development in Humans.

PMID- 27050925
TI  - Patient experience and hospital profitability: Is there a link?
AB  - BACKGROUND: Patient experience has had a direct financial impact on hospitals
      since value-based purchasing was instituted by the Centers for Medicare &
      Medicaid Services in 2013 as a method to reward or punish hospitals based on
      performance on various measures, including patient experience. Although other
      industries have shown an indirect impact of customer experience on overall
      profitability, that link has not been well established in the health care
      industry. Return-to-provider rate and perceptions of health quality have been
      associated with profitability in the health care industry. PURPOSE: Our aims were
      to assess whether, independent of a direct financial impact, a more positive
      patient experience is associated with increased profitability and whether a more
      negative patient experience is associated with decreased profitability.
      METHODOLOGY/APPROACH: We used a sample of 19,792 observations from 3767 hospitals
      over the 6-year period 2007-2012. The data were sourced from Centers for Medicare
      & Medicaid Services and Hospital Consumer Assessment of Healthcare Providers and
      Systems. Using generalized estimating equations to account for repeated measures,
      we fit four separate models for three dependent variables: net patient revenue,
      net income, and operating margin. Each model included one of the following
      independent variables of interest: percentage of patients who definitely
      recommend the hospital, percentage of patients who definitely would not recommend
      the hospital, percentage of patients who rated the hospital 9 or 10, and
      percentage of patients who rated the hospital 6 or lower. FINDINGS: We identified
      that a positive patient experience is associated with increased profitability and
      a negative patient experience is even more strongly associated with decreased
      profitability. PRACTICE IMPLICATIONS: Management should have greater
      justification for incurring costs associated with bolstering patient experience
      programs. Improvements in training, technology, and staffing can be justified as
      a way to improve not only quality but now profitability as well.

PMID- 27050926
TI  - Evidence that electronic health records can promote physician counseling for
      healthy behaviors.
AB  - BACKGROUND: Health behavior counseling services may help patients manage chronic
      conditions effectively and slow disease progression. Studies show, however, that
      many providers fail to provide these services because of time constraints and
      inability to tailor counseling to individual patient needs. Electronic health
      records (EHRs) have the potential to increase appropriate counseling by providing
      pertinent patient information at the point of care and clinical decision support.
      PURPOSE: This study estimates the impact of select EHR functionalities on the
      rate of health behavior counseling provided during primary care visits.
      METHODOLOGY: Multivariable regression analyses of the 2007-2010 National
      Ambulatory Medical Care Survey were conducted to examine whether eight EHR
      components representing four core functionalities of EHR systems were correlated
      with the rate of health behavior counseling services. Propensity score matching
      was used to control for confounding factors given the use of observational data.
      To address concerns that EHR may only lead to improved documentation of
      counseling services and not necessarily improved care, the association of EHR
      functionalities with prescriptions for smoking cessation medications was also
      estimated. FINDINGS: The use of an EHR system with health information and data,
      order entry and management, result management, decision support, and a
      notification system for abnormal test results was associated with an
      approximately 25% increase in the probability of health behavior counseling
      delivered. Clinical reminders were associated with more health behavior
      counseling services when available in combination with patient problem lists. The
      laboratory results viewer was also associated with more counseling services when
      implemented with a notification system for abnormal results. PRACTICE
      IMPLICATION: An EHR system with key supportive functionalities can enhance
      delivery of preventive health behavior counseling services in primary care
      settings. Meaningful use criteria should be evaluated to ensure that they
      encourage the adoption of EHR systems with those functionalities shown to improve
      clinical care.

PMID- 27050927
TI  - The strategic nature of individual change behavior: How physicians and their
      staff implement medical home care.
AB  - BACKGROUND: The patient-centered medical home (PCMH) model of care is central to
      primary care system success and transformation. Less is known about which PCMH
      activities primary care workers most frequently perform, if or why they might
      view that work more favorably, and how such work may function strategically to
      advance individual and organizational adaptation to new demands, as well as
      deliver good patient care. PURPOSE: Understanding better how primary care
      physicians and staff perceive, experience, and use certain types of PCMH work for
      adapting to new demands looms a key imperative for gaining insights into PCMH
      implementation at the workplace level. METHODS: Using a worker adaptation
      perspective that emphasizes the role of social learning and individual agency,
      this study explores the strategic nature of PCMH implementation through 51 in
      depth interviews with physicians and staff in six accredited PCMHs. FINDINGS:
      Select medical home activities were identified, in which primary care physicians
      and staff most engaged on a daily basis, and they fell into five distinct PCMH
      work domains labeled team care, medical home responsibilities, care management,
      access, and medication management. These activities had common features such as
      high levels of familiarity, simplicity, and camaraderie. In addition, through
      their experiences performing these activities, physicians and staff appeared to
      gain strategic benefits for themselves and the larger organization including
      enhanced self-efficacy and readiness for change. CONCLUSIONS: The findings show
      that particular forms of PCMH work not only advance patient care in favorable
      ways but also enhance individual and organizational capacity for adapting to this
      innovative model and its demands. This knowledge adds to our understanding of how
      to implement PCMH care in ways that are good for workers, primary care
      organizations, and patients and offers practical guidance as to which forms of
      PCMH work should be encouraged, incented, and rewarded.

PMID- 27050928
TI  - Technically unresectable recurrent oral cancers: Is NACT the answer?

PMID- 27050929
TI  - ANA testing in the presence of acute and chronic infections.
AB  - Autoantibody testing is performed to help diagnose patients who have clinical
      symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA)
      are present in many systemic autoimmune conditions such as systemic lupus
      erythematosus (SLE). However, a positive ANA test may also be seen with non
      autoimmune inflammatory diseases, including both acute and chronic infections.
      When the ANA test is used as an initial screen in patients with non-specific
      clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia,
      the likelihood of a positive result due to infection will increase, especially in
      children. This article identifies acute and chronic infectious diseases that are
      likely to produce a positive ANA result and summarizes recent literature
      addressing both the causes and consequences of these findings. 

PMID- 27050930
TI  - Circular RNA Expression: Its Potential Regulation and Function.
AB  - In 2012, a new feature of eukaryotic gene expression emerged: ubiquitous
      expression of circular RNA (circRNA) from genes traditionally thought to express
      messenger or linear noncoding (nc)RNA only. CircRNAs are covalently closed,
      circular RNA molecules that typically comprise exonic sequences and are spliced
      at canonical splice sites. This feature of gene expression was first recognized
      in humans and mouse, but it quickly emerged that it was common across essentially
      all eukaryotes studied by molecular biologists. CircRNA abundance, and even which
      alternatively spliced circRNA isoforms are expressed, varies by cell type and can
      exceed the abundance of the traditional linear mRNA or ncRNA transcript. CircRNAs
      are enriched in the brain and increase in abundance during fetal development.
      Together, these features raise fundamental questions regarding the regulation of
      circRNA in cis and in trans, and its function.

PMID- 27050931
TI  - Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.
AB  - N(6)-Methyladenosine (m(6)A) is emerging as a chemical mark that broadly affects
      the flow of genetic information in various biological processes in eukaryotes.
      Recently, Xiao et al. reported that the nuclear m(6)A reader protein YTHDC1
      impacts mRNA splicing, providing a transcriptome-wide glance of splicing changes
      affected by this mRNA methylation reader protein.

PMID- 27050932
TI  - New advances in the treatment of generalized anxiety disorder: the multimodal
      antidepressant vortioxetine.
AB  - Generalized Anxiety Disorder (GAD) is a persistent condition characterized by
      chronic anxiety, exaggerated worry and tension, mainly comorbid with Major
      Depressive Disorder (MDD). Currently, selective serotonin reuptake inhibitors and
      serotonin-norepinephrine reuptake inhibitors are recommended as first-line
      treatment of GAD. However, some patients may not respond to the treatment or
      discontinue due to adverse effects. Vortioxetine (VRX) is a multimodal
      antidepressant with a unique mechanism of action, by acting as 5-HT3A, 5-HT1D and
      5-HT7 receptor antagonist, partial agonist at the 5-HT1A and 5-HT1B receptors and
      inhibitor at the 5-HT transporter. Preliminary clinical trials showed contrasting
      findings in terms of improvement of the anxiety symptomatology and/or cognitive
      impairment. Here, we aim to systematically review the evidence currently
      available on the efficacy, safety and tolerability of VRX in the treatment of
      GAD. The generalizability of results on the efficacy of VRX in patients with
      anxiety symptomatology and GAD is limited due to few and contrasting RCTs so far
      available. Only two studies, of which one prevention relapse trial, reported a
      significant improvement in anxiety symptomatology compared to three with negative
      findings.

PMID- 27050933
TI  - Enhancing thermoelectric performance of Bi2Te3-based nanostructures through
      rational structure design.
AB  - Nanostructuring has been successfully employed to enhance the thermoelectric
      performance of Bi2Te3 due to its obtained low thermal conductivity. In order to
      further reduce the thermal conductivity, we designed a hierarchical nanostructure
      assembled with well-aligned Bi2Te3 nanoplates using Te nanotubes as templates by
      a facile microwave-assisted solvothermal synthesis. From the comparisons of their
      thermoelectric performance and theoretical calculations with simple Bi2Te3
      nanostructures, we found that Te/Bi2Te3 hierarchical nanostructures exhibit a
      higher figure-of-merit due to the optimized reduced Fermi level and enhanced
      phonon scattering, as well as the suppressed bipolar conduction. This study
      provides an effective approach to enhance the thermoelectric performance of
      Bi2Te3-based nanostructures by rationally designing the nanostructures. 

PMID- 27050934
TI  - Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries
      through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas
      receptor axis.
AB  - The role of the Mas receptor in the activity of valsartan against intimal
      hyperplasia is unclear. Herein, we investigated the role of the angiotensin
      converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of
      valsartan against intimal hyperplasiain balloon-injured rat aortic arteries.
      Wistar rats were randomized equally into the sham control group, injured group,
      and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly
      attenuated the vascular smooth muscle cell proliferation and intimal and medial
      thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well
      as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in
      the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II
      level as well as the ACE and AT1 receptor mRNA/protein expression were increased
      (all P < 0.05 or < 0.01). Additionally, the p-ERK protein expression was
      increased (P < 0.01). Treatment with valsartan significantly increased the
      angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression
      but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein
      expression, as well as the p-ERK protein expression, compared to the injured
      group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates
      neointimal hyperplasiain balloon-injured rat aortic arteries through activation
      of the ACE2-angiotensin-(1-7)-Mas axis as well as inhibition of the ACE
      angiotensin II-AT1 and p-ERK pathways.

PMID- 27050935
TI  - Breastfeeding, bottle feeding and risk of malocclusion in mixed and permanent
      dentitions: a systematic review.
AB  - The aim of the present study was to search for scientific evidence concerning the
      association between breastfeeding and bottle feeding and risk of malocclusion in
      mixed and permanent dentitions. An electronic search was performed in eight
      databases up to February 2015. Additionally, a gray literature search and hand
      searches of the reference lists of the selected studies were also carried out.
      There were no restrictions on language or on year of publication. The methodology
      of the included articles was evaluated using the Newcastle Ottawa scale. Out of
      the 817 identified citations, six studies fulfilled the eligibility criteria and
      were included in the systematic review. One study showed that children with mixed
      and permanent dentitions breastfed for more than 6 months presented greater mean
      protrusion of mandibular incisors and inclination of maxillary incisors compared
      with those breastfed for less than 6 months or those who were bottle-fed (p <
      0.05). One study revealed that breastfeeding and bruxism were associated with
      Class II [OR = 3.14 (1.28 - 7.66)] and Class III [OR = 2.78 (1.21 - 6.36)]
      malocclusion in children with permanent dentition, while another study showed
      that an increase in breastfeeding duration was associated with a lower risk of
      malocclusion in children with both mixed and permanent dentitions (p < 0.001).
      Three studies did not report any significant association. Risk of bias was high
      in most selected articles. These findings do not support an association between
      breastfeeding and bottle feeding and the occurrence of malocclusion in mixed and
      permanent dentitions. 

PMID- 27050936
TI  - Volume of sealer in the apical region of teeth filled by different techniques: a
      micro-CT analysis.
AB  - The volume of sealer in the apical 1 mm of teeth filled using different
      techniques was evaluated by micro-commuted tomography (micro-CT). Sixty-four
      maxillary central incisors were prepared using NiTi rotary instruments. Teeth
      were randomly distributed into four groups according to root canal sealers (AH
      Plus, Endofill, Sealapex, and Sealer 26) and subdivided into two subgroups
      according to the filling techniques (active and passive lateral condensation; n =
      8 each). Subsequently, teeth were examined using the 1174 SkyScan micro-CT
      device. Images were reconstructed using the NRecon software, and the sealer
      volume (mm3) in the apical region was analyzed using the two-way ANOVA and post
      hoc Student-Newman-Keuls test (alpha = 0.05). The lowest volume of sealer was
      observed in teeth filled with Sealapex (0.100 +/- 0.009) and Endofill (0.103 +/-
      0.010). The highest volume was observed in teeth filled with AH Plus (0.112 +/-
      0.008) and Sealer 26 (0.109 +/- 0.018) (p > 0.05). Regarding the filling
      technique, a lower sealer volume was observed using the active lateral
      condensation technique compared with that using the passive lateral condensation
      technique (0.100 +/- 0.010 vs. 0.111 +/- 0.012) (p < 0.05). Therefore, the lowest
      volume of sealer was observed in teeth filled with Sealapex and Endofill using
      the active lateral condensation technique.

PMID- 27050937
TI  - Fluoride rinse effect on retention of CaF2 formed on enamel/dentine by fluoride
      application.
AB  - Calcium fluoride-like materials ("CaF2") formed on dental surfaces after
      professional fluoride application are unstable in the oral environment but can be
      retained longer with a daily NaF mouthrinse. We tested the effect of twice daily
      0.05% NaF rinses on the retention of "CaF2" formed on enamel and dentine after
      applying acidulated phosphate fluoride (APF). "CaF2" formed on enamel/dentine by
      APF application significantly decreased after exposure to artificial saliva and
      the 0.05% NaF rinse was ineffective to avoid this reduction. These findings
      suggest that the combination of APF and 0.05% NaF is not clinically relevant,
      either for caries or dental hypersensitivity. 

PMID- 27050938
TI  - Analysis of Interleukin 17A in periapical abscess and granuloma lesions.
AB  - Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the
      initiation and propagation of inflammation. One of its actions is the recruitment
      of neutrophils to the site of infection. The aim of this study was to investigate
      whether there is association between IL-17A expression and neutrophil
      infiltration in periapical abscesses and periapical granulomas, as well as to
      find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these
      lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and
      immunofluorescence, in the biopsies of periapical lesions. Abscess lesions
      exhibited the highest labeling area for IL-17A (p = 0.011). During double
      immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells
      compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas
      (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical
      abscesses rich in neutrophils. The high percentage of IL-17A in these cases
      suggests the participation of this cytokine particularly in the acute stages of
      the inflammatory process of the periapical lesions. 

PMID- 27050939
TI  - Influence of different fillers on the properties of an experimental vinyl
      polysiloxane.
AB  - The aim of the study was to evaluate the effect of the incorporation of different
      fillers on an experimental vinyl polysiloxane (VPS) at two different
      concentrations, 20% and 40%. Different fillers were added to an experimental VPS.
      The study was developed in two stages: (i) incorporation of fillers in different
      concentrations: (a) 20 wt% fillers, and (b) 40 wt%. The fillers were added to
      experimental VPS and mixed with a speed mixer; (ii) characterization of
      experimental VPS; after the base paste and catalyst paste were mixed, the
      experimental VPS was used to make specimens specifically for each test, which
      were stored at 23 degrees C for 24 hours. The tests were designed according to
      the specific standardization for the analysis of tensile strength, detail
      reproduction, Shore A hardness, and elastic recovery. For analysis of filler size
      pattern, scanning electron microscopy at 1500* magnification was used. The
      aerosil OX-50 40% (AE), and pure aluminum hydroxide 40% (PAH) groups presented
      the highest tensile strength and Shore A hardness values. However, those were the
      only groups that did not present continuous detail reproduction of an
      intersection of 20 MUm line. The elastic recovery was not statistically
      significant. The undesirable characteristics of VPS (lowest Shore A hardness and
      tensile strength) were observed when it was added to the composition of acrylic
      polymer (AP) and fiberglass (FG) in both concentrations, 20% and 40%. In groups
      AE and PAH, agglomerates of nanofillers were shown in SEM micrography, while the
      other groups presented different shapes and fillers sizes. 

PMID- 27050940
TI  - Effect of filling technique on the bond strength of methacrylate and silorane
      based composite restorations.
AB  - The bond strength of methacrylate (Z350, 3M ESPE) and silorane (P90, 3M ESPE)
      restorations, using different cavity filling techniques, was investigated.
      Cavities (6 * 3 * 3) in bovine teeth were filled using bulk, oblique, or
      horizontal increments. A push-out test was carried out after 24 h. Data were
      statistically analyzed (alpha = 5%). Methacrylate-based composites and the
      horizontal filling technique showed the highest bond strength values (10.2 +/-
      3.9, p < 0.05). Silorane-based composites showed no statistically significant
      differences regarding the filling techniques (p > 0.05). 

PMID- 27050941
TI  - Causes of delayed diagnoses of cancers in Japan from the viewpoint of malpractice
      litigations.

PMID- 27050942
TI  - Endoscopic scores for inflammatory bowel disease in the era of 'mucosal healing':
      Old problem, new perspectives.
AB  - The importance of the endoscopic evaluation in inflammatory bowel disease (IBD)
      management has been recognized for many years. However, the modalities for
      reporting endoscopic activity represent an ongoing challenge. To address this,
      several endoscopic scores have been proposed. Very few have been properly
      validated, and the use of such tools remains sub-optimal and is mainly restricted
      to clinical trials. In recent years, a growing emphasis of the concept of
      'mucosal healing' as a prognostic marker and therapeutic goal has increased the
      need for a more accurate definition of endoscopic activity in both ulcerative
      colitis (UC) and Crohn's Disease (CD). In the present review, the evolution of
      the challenges related to endoscopic scores in IBD has been analyzed, with
      particular attention paid to the renewed relevance of endoscopic activity in
      recent years. Currently, despite the growing relevance of endoscopic activity,
      evaluating this activity in IBD is still a challenge. The implementation of
      efficacious endoscopic scores and a better definition of the absence of activity
      (mucosal healing) are needed. 

PMID- 27050943
TI  - Manipulating interface states in monolayer-bilayer graphene planar junctions.
AB  - We report on transport properties of monolayer-bilayer graphene planar junctions
      in a magnetic field. Due to its unique geometry, the edge and interface states
      can be independently manipulated by either interlayer potential or Zeeman field,
      and the conductance exhibits interesting quantized behaviors. In the hybrid
      graphene junction, the quantum Hall (QH) conductance is no longer antisymmetric
      with respect to the charge neutrality point. When the Zeeman field is considered,
      a quantum spin Hall (QSH) phase is found in the monolayer region while the weak
      QSH phase stays in the bilayer region. In the presence of both interlayer
      potential and Zeeman field, the bilayer region hosts a QSH phase, whereas the
      monolayer region is still in a QH phase, leading to a spin-polarized current in
      the interface. In particular, the QSH phase remains robust against the disorder. 

PMID- 27050944
TI  - Categorization of common sounds by cochlear implanted and normal hearing adults.
AB  - Auditory categorization involves grouping of acoustic events along one or more
      shared perceptual dimensions which can relate to both semantic and physical
      attributes. This process involves both high level cognitive processes
      (categorization) and low-level perceptual encoding of the acoustic signal, both
      of which are affected by the use of a cochlear implant (CI) device. The goal of
      this study was twofold: I) compare the categorization strategies of CI users and
      normal hearing listeners (NHL) II) investigate if any characteristics of the raw
      acoustic signal could explain the results. 16 experienced CI users and 20 NHL
      were tested using a Free-Sorting Task of 16 common sounds divided into 3
      predefined categories of environmental, musical and vocal sounds. Multiple
      Correspondence Analysis (MCA) and Hierarchical Clustering based on Principal
      Components (HCPC) show that CI users followed a similar categorization strategy
      to that of NHL and were able to discriminate between the three different types of
      sounds. However results for CI users were more varied and showed less inter
      participant agreement. Acoustic analysis also highlighted the average pitch
      salience and average autocorrelation peak as being important for the perception
      and categorization of the sounds. The results therefore show that on a broad
      level of categorization CI users may not have as many difficulties as previously
      thought in discriminating certain kinds of sound; however the perception of
      individual sounds remains challenging.

PMID- 27050945
TI  - Acidosis-Induced Hypochloremic Alkalosis in Diabetic Ketoacidosis Confirmed by
      The Modified Base Excess Method.
AB  - CONTEXT AND OBJECTIVE: Diabetic ketoacidosis (DKA) is associated with a metabolic
      alkalosis, which is thought to be due to vomiting. However, alkalosis can occur
      in DKA without vomiting. We retrospectively reviewed the acid-base disturbances
      in DKA admissions without vomiting. PARTICIPANTS AND METHODS: We included
      admissions of the patients with blood glucose and beta-hydroxybutyrate (betaOHB)
      levels > 250 mg/dL and > 1.0 mmol/L, respectively. Admissions without vomiting
      were classified into a group with a betaOHB > 3.0 mmol/L (DKA group) and a group
      with betaOHB of 1.0-3.0 mmol/L (pre-DKA group). The acid-base status was analyzed
      by the modified base excess (BE) method. BE effects were calculated by changes in
      sodium (BE free water, [BEFW]), and chloride (BECl). Positive and negative values
      for each parameter suggested alkalosis and acidosis, respectively. RESULTS: Forty
      five included admissions were divided into DKA (n = 34) and pre-DKA (n =11)
      groups. Sodium-corrected chloride level and the chloride/sodium ratio were
      significantly lower in the DKA group than in the pre-DKA group. In both groups,
      BEFW values were modestly negative. The mean BECl values were positive in both
      groups, but significantly higher in the DKA group. The alkalinizing effects by
      hypochloremia diminished the base deficit in the DKA group by approximately 25%.
      The BECl value significantly correlated with serum total ketone levels (r = 0.66;
      P < .0001). CONCLUSION: The modified BE method successfully proved the presence
      of hypochloremic alkalosis in DKA without vomiting. This suggests the direct
      participation of serum ketoacids in the pathogenesis of hypochloremic alkalosis.

PMID- 27050946
TI  - Expression of asthma susceptibility genes in bronchial epithelial cells and
      bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort.
AB  - OBJECTIVE: Genome-wide association studies (GWASs) have identified genes
      associated with asthma, however expression of these genes in asthma-relevant
      tissues has not been studied. This study tested expression and correlation
      between GWAS-identified asthma genes and asthma or asthma severity. METHODS:
      Correlation analyses of expression levels of GWAS-identified asthma genes and
      asthma-related biomarkers were performed in cells from human bronchial epithelial
      biopsy (BEC, n = 107) and bronchial alveolar lavage (BAL, n = 94). RESULTS:
      Expression levels of asthma genes between BEC and BAL and with asthma or asthma
      severity were weakly correlated. The expression levels of IL18R1 were
      consistently higher in asthma than controls or in severe asthma than
      mild/moderate asthma in BEC and BAL (p < 0.05). In RAD50-IL13 region, the
      expression levels of RAD50, not IL4, IL5, or IL13, were positively correlated
      between BEC and BAL (rho = 0.53, P = 4.5 * 10(-6)). The expression levels of IL13
      were positively correlated with IL5 in BEC (rho = 0.35, P = 1.9 * 10(-4)) and IL4
      in BAL (rho = 0.42, P = 2.5 * 10(-5)), respectively. rs3798134 in RAD50, a GWAS
      identified SNP, was correlated with IL13 expression and the expression levels of
      IL13 were correlated with asthma (P = 0.03). rs17772583 in RAD50 was
      significantly correlated with RAD50 expression in BAL and BEC (P = 7.4 * 10(-7)
      and 0.04) but was not associated with asthma. CONCLUSIONS: This is the first
      report studying the expression of GWAS-identified asthma genes in BEC and BAL.
      IL13, rather than RAD50, IL4, or IL5, is more likely to be the asthma
      susceptibility gene. Our study illustrates tissue-specific expression of asthma
      related genes. Therefore, whenever possible, disease-relevant tissues should be
      used for transcription analysis.

PMID- 27050947
TI  - Dynamic Transcriptional and Epigenetic Regulation of Human Epidermal Keratinocyte
      Differentiation.
AB  - Human skin is maintained by the differentiation and maturation of interfollicular
      stem and progenitors cells. We used DeepCAGE, genome-wide profiling of histone
      modifications and retroviral integration analysis, to map transcripts, promoters,
      enhancers, and super-enhancers (SEs) in prospectively isolated keratinocytes and
      transit-amplifying progenitors, and retrospectively defined keratinocyte stem
      cells. We show that >95% of the active promoters are in common and differentially
      regulated in progenitors and differentiated keratinocytes, while approximately
      half of the enhancers and SEs are stage specific and account for most of the
      epigenetic changes occurring during differentiation. Transcription factor (TF)
      motif identification and correlation with TF binding site maps allowed the
      identification of TF circuitries acting on enhancers and SEs during
      differentiation. Overall, our study provides a broad, genome-wide description of
      chromatin dynamics and differential enhancer and promoter usage during epithelial
      differentiation, and describes a novel approach to identify active regulatory
      elements in rare stem cell populations.

PMID- 27050948
TI  - Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate
      Retinogenesis.
AB  - The plasticity of pluripotent stem cells provides new possibilities for studying
      development, degeneration, and regeneration. Protocols for the differentiation of
      retinal organoids from embryonic stem cells have been developed, which either
      recapitulate complete eyecup morphogenesis or maximize photoreceptor genesis.
      Here, we have developed a protocol for the efficient generation of large, 3D
      stratified retinal organoids that does not require evagination of optic-vesicle
      like structures, which so far limited the organoid yield. Analysis of gene
      expression in individual organoids, cell birthdating, and interorganoid variation
      indicate efficient, reproducible, and temporally regulated retinogenesis.
      Comparative analysis of a transgenic reporter for PAX6, a master regulator of
      retinogenesis, shows expression in similar cell types in mouse in vivo, and in
      mouse and human retinal organoids. Early or late Notch signaling inhibition
      forces cell differentiation, generating organoids enriched with cone or rod
      photoreceptors, respectively, demonstrating the power of our improved organoid
      system for future research in stem cell biology and regenerative medicine.

PMID- 27050949
TI  - Lysophosphatidic Acid Receptor Is a Functional Marker of Adult Hippocampal
      Precursor Cells.
AB  - Here, we show that the lysophosphatidic acid receptor 1 (LPA1) is expressed by a
      defined population of type 1 stem cells and type 2a precursor cells in the adult
      mouse dentate gyrus. LPA1, in contrast to Nestin, also marks the quiescent stem
      cell population. Combining LPA1-GFP with EGFR and prominin-1 expression, we have
      enabled the prospective separation of both proliferative and non-proliferative
      precursor cell populations. Transcriptional profiling of the isolated
      proliferative precursor cells suggested immune mechanisms and cytokine signaling
      as molecular regulators of adult hippocampal precursor cell proliferation. In
      addition to LPA1 being a marker of this important stem cell population, we also
      show that the corresponding ligand LPA is directly involved in the regulation of
      adult hippocampal precursor cell proliferation and neurogenesis, an effect that
      can be attributed to LPA signaling via the AKT and MAPK pathways.

PMID- 27050950
TI  - Impairing the useful field of view in natural scenes: Tunnel vision versus
      general interference.
AB  - A fundamental issue in visual attention is the relationship between the useful
      field of view (UFOV), the region of visual space where information is encoded
      within a single fixation, and eccentricity. A common assumption is that impairing
      attentional resources reduces the size of the UFOV (i.e., tunnel vision).
      However, most research has not accounted for eccentricity-dependent changes in
      spatial resolution, potentially conflating fixed visual properties with flexible
      changes in visual attention. Williams (1988, 1989) argued that foveal loads are
      necessary to reduce the size of the UFOV, producing tunnel vision. Without a
      foveal load, it is argued that the attentional decrement is constant across the
      visual field (i.e., general interference). However, other research asserts that
      auditory working memory (WM) loads produce tunnel vision. To date, foveal versus
      auditory WM loads have not been compared to determine if they differentially
      change the size of the UFOV. In two experiments, we tested the effects of a
      foveal (rotated L vs. T discrimination) task and an auditory WM (N-back) task on
      an extrafoveal (Gabor) discrimination task. Gabor patches were scaled for size
      and processing time to produce equal performance across the visual field under
      single-task conditions, thus removing the confound of eccentricity-dependent
      differences in visual sensitivity. The results showed that although both foveal
      and auditory loads reduced Gabor orientation sensitivity, only the foveal load
      interacted with retinal eccentricity to produce tunnel vision, clearly
      demonstrating task-specific changes to the form of the UFOV. This has theoretical
      implications for understanding the UFOV. 

PMID- 27050951
TI  - Comparative RNA profile analysis of idiopathic dilated cardiomyopathy and
      ischemic cardiomyopathy.
AB  - Previous research has focused on revealing the functions of each individual gene
      and/or pathway in idiopathic dilated cardiomyopathy (DCM) or ischemic
      cardiomyopathy (IC). However, the common or specific pathways of the initiation
      and processes of DCM and IC are still unclear. Here, we attempted to uncover the
      critical genes and potential molecular networks that play important roles in DCM
      and IC progression commonly or specifically. The transcriptional profiles from
      normal and DCM or IC patient samples were analyzed and compared using
      bioinformatic methods. Initially, the normal and DCM or IC sample data were
      processed and the most notable differentially expressed genes (DEGs) from DCM or
      IC were identified. By comparing the DEGs from DCM with those from IC, the DCM-
      and IC-specific DEGs were identified. The gene ontology and Kyoto Encyclopedia of
      Genes and Genomes pathway analyses indicated the significance of multiple
      biological processes as well as signaling pathways that affect heart function and
      DCM or IC progression. Protein-protein interaction network analysis identified
      the relationships between different genes, and some important genes such as MYC
      and FN1 were found to be hubs, which master each individual module of DCM
      specific and IC-specific DEGs, respectively. We discovered commonalities and
      differences of gene expression profiles and molecular pathways between different
      cardiomyopathies. The gene discovery and molecular signature analysis in this
      study could offer insights into disease mechanisms and also identify markers
      useful for diagnostic, prognostic, and therapeutic purposes. 

PMID- 27050952
TI  - Tumor necrosis factor-like weak inducer of apoptosis association with
      proliferative diabetic retinopathy and promotes proliferation and collagen
      synthesis in retinal ARPE-19 cells.
AB  - Chronic inflammation develops in the retinal microvasculature under sustained
      hyperglycemia and is implicated in the pathogenesis of diabetic retinopathy.
      Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor
      Fn14 have been reported to promote pro-inflammatory cytokines, which are involved
      in the pathogenesis of proliferative diabetic retinopathy (PDR). It is therefore
      possible that the TWEAK/Fn14 pathway can play a regulatory role in PDR. In the
      present study, we examined the expression of TWEAK and Fn14 in vitreous fluid
      from PDR patients. To confirm the correlation between the TWEAK expression and
      clinical pathological characteristics of PDR, we investigated the regulatory role
      of the TWEAK/Fn14 pathway in cell proliferation and collagen synthesis in retinal
      ARPE-19 cells. The results demonstrated that vitreous fluid from patients with
      PDR had higher levels of TWEAK and Fn14 than that from T2DM patients without PDR,
      thus suggesting an important regulatory role of TWEAK/Fn14 signaling in the
      pathogenesis of PDR. Furthermore, overexpression of TWEAK in ARPE-19 cells also
      promoted proliferation of and collagen synthesis in these retinal cells. It is
      possible that TWEAK/Fn14 upregulation in PDR may contribute to PDR progression by
      promoting the proliferation or fibrosis of retinal cells. 

PMID- 27050953
TI  - Role of single nucleotide polymorphisms of DNA repair genes in susceptibility to
      pancreatic cancer in Chinese population.
AB  - We conducted a case-control study to investigate the role of ERCC1-ERCC5 gene
      polymorphisms in the risk of pancreatic cancer. This study included 195 patients
      who were newly diagnosed with histopathologically confirmed primary pancreatic
      cancer, and 254 controls were recruited from Sir Run Run Shaw Hospital, between
      January 2012 and December 2014. Genotyping of ERCC1 rs3212986 and rs11615, ERCC2
      rs13181, ERCC3 rs4150441, ERCC4 rs6498486, and ERCC5 rs2094258 polymorphisms was
      carried out using polymerase chain reaction coupled with restriction fragment
      length polymorphism. Unconditional logistic regression analyses showed that the
      TT genotype of ERCC1 rs3212986 was associated with an increased risk of
      pancreatic cancer, and the OR (95%CI) was 2.26 (1.21-4.22). However, we did not
      find a significant association between ERCC1 rs11615, ERCC2 rs13181, ERCC3
      rs4150441, ERCC4 rs6498486, and ERCC5 rs2094258 polymorphisms and risk of
      pancreatic cancer. In summary, we found that the presence of the ERCC1 rs3212986
      polymorphism correlated with an increased risk of pancreatic cancer. 

PMID- 27050954
TI  - Genome sequencing and systems biology analysis of a lipase-producing bacterial
      strain.
AB  - Lipase-producing bacteria are naturally-occurring, industrially-relevant
      microorganisms that produce lipases, which can be used to synthesize biodiesel
      from waste oils. The efficiency of lipase expression varies between various
      microbial strains. Therefore, strains that can produce lipases with high
      efficiency must be screened, and the conditions of lipase metabolism and
      optimization of the production process in a given environment must be thoroughly
      studied. A high efficiency lipase-producing strain was isolated from the
      sediments of Jinsha River, identified by 16S rRNA sequence analysis as Serratia
      marcescens, and designated as HS-L5. A schematic diagram of the genome sequence
      was constructed by high-throughput genome sequencing. A series of genes related
      to lipid degradation were identified by functional gene annotation through
      sequence homology analysis. A genome-scale metabolic model of HS-ML5 was
      constructed using systems biology techniques. The model consisted of 1722 genes
      and 1567 metabolic reactions. The topological graph of the genome-scale metabolic
      model was compared to that of conventional metabolic pathways using a
      visualization software and KEGG database. The basic components and boundaries of
      the tributyrin degradation subnetwork were determined, and its flux balance
      analyzed using Matlab and COBRA Toolbox to simulate the effects of different
      conditions on the catalytic efficiency of lipases produced by HS-ML5. We proved
      that the catalytic activity of microbial lipases was closely related to the
      carbon metabolic pathway. As production and catalytic efficiency of lipases
      varied greatly with the environment, the catalytic efficiency and environmental
      adaptability of microbial lipases can be improved by proper control of the
      production conditions. 

PMID- 27050955
TI  - A diagnostic kit for the enteroviruses Coxsackie A6 and A10.
AB  - Recently, there has been an upward trend in the occurrence of hand-foot-mouth
      disease, which is correlated with Coxsackie A6 and A10 infections. Although two
      separate diagnostic reagents are available for these two viral strains, the
      protocol and diagnosis efficiency still need to be improved. More importantly, as
      co-infection with these viruses is common, the development of a single test kit
      that can diagnose both viruses would be most beneficial for clinical practice. In
      our study, specific primers targeting viral nucleic acids were designed and
      modified. Viral nucleic acids were extracted from fecal or throat swab samples by
      ultrasonic rupture and silicon membrane purification. The consistency,
      specificity, and sensitivity of the tests were further optimized by adjusting the
      polymerase chain reaction (PCR) conditions. The efficiency of viral nucleic acid
      extraction was significantly enhanced by the ultrasonic rupture and silicon
      membrane elution approach. Specific amplifications of both viral nucleic acids
      were achieved using modified primers. The optimal conditions for PCR were also
      determined (60 degrees C for 30 min and 95 degrees C for 2 min, followed by 40
      cycles of denaturation for 30 s at 95 degrees C, annealing for 30 s at 60 degrees
      C, and elongation for 50 s at 72 degrees C). Amplified products were confirmed as
      viral specific nucleotides by agarose gel electrophoresis and sequencing. The
      minimal nucleic acid concentration required for detection was 0.2 ng/L, which was
      adequate to yield satisfactory specificity and consistency. This novel diagnostic
      method has many advantages, including rapid protocols and accurate results, and
      can be promoted for large-scale clinical trials. 

PMID- 27050956
TI  - Roles of osteocyte apoptosis in steroid-induced avascular necrosis of the femoral
      head.
AB  - An animal model of steroid-induced avascular necrosis of the femoral head (SANFH)
      was established to investigate the roles of osteocyte apoptosis in this process.
      Forty five-month-old male and female Japanese white rabbits were randomly divided
      into groups A (hormone + endotoxin), B (hormone alone), C (endotoxin alone), and
      D (blank control). Animals were sacrificed two and four weeks following the final
      treatment (N = 5 for each group at each time point). Bilateral femoral heads were
      fixed and decalcified, and empty lacunae were counted by hematoxylin staining. At
      weeks 2 and 4, the empty lacunae percentage was significantly higher in group A
      than that in groups B, C, or D (P < 0.01), while no significant difference was
      observed between these latter three. At week 2, all osteocyte apoptosis indexes
      were within normal ranges in all the groups, which therefore did not
      significantly differ in this respect (P > 0.05). However, at week 4, the
      apoptotic index was significantly higher in group A than that in groups B, C, or
      D (P < 0.01), comparisons between which revealed no such differences. Moreover, a
      positive correlation was observed between the percentage of empty lacunae and the
      apoptotic index at week 4 in group A (r = 0.893). We conclude that osteocyte
      apoptosis plays an important role in SANFH. 

PMID- 27050957
TI  - Gene expression changes in chicken NLRC5 signal pathway associated with in vitro
      avian leukosis virus subgroup J infection.
AB  - Nucleotide-binding oligomerization domain-like receptors (NLRs) play a key role
      in the innate immune response as pattern-recognition receptors. However, the role
      of NLRC5, which is a member of the NLR family, in NF-kappaB activation and MHC-I
      expression remains debatable. Infection with the J group avian leukosis virus
      (ALV-J) can result in immunosuppression and a subsequent increase in
      susceptibility to secondary infection. This results in huge economic losses to
      the poultry industry worldwide. Using quantitative real-time polymerase chain
      reaction (qRT-PCR), we investigated the mRNA expression levels of NLRC5 signal
      pathway-related genes in secondary chicken embryo fibroblasts 7 days after
      infection with ALV-J. The results indicated that, compared with the control
      groups, the expression levels of TLR7, MHC-I, and IL-18 increased significantly
      in the infected groups at 7 days post-infection (d.p.i.). The expression levels
      of NLRC5 and IL-6 were conspicuously downregulated at 7 d.p.i., but the
      expression levels of NF-kappaB, STAT1, and STAT3 were not significantly altered.
      These results suggest that NLRC5 and some genes involved in the NLRC5 pathway
      play a key role in antiviral immunity, typically the response to ALV-J infection.
      Moreover, MHC-I expression levels vary between different cell types. 

PMID- 27050958
TI  - Mechanism of SEMA3B gene silencing and clinical significance in glioma.
AB  - The aim of the current study was to explore mechanisms of SEMA3B gene expression
      and its clinical significance in glioma, and provide a theoretical foundation for
      investigating individualized treatment in glioma. Paraffin-embedded tissues from
      43 patients with a confirmed clinical diagnosis of glioma following neurosurgery
      at the First Affiliated Hospital of Zhengzhou University from December 2013 to
      April 2014 were selected randomly. An additional three normal brain tissues were
      obtained following encephalic decompression excision due to acute craniocerebral
      injury in the same period, which were used as the control group.
      Immunohistochemical staining for vascular endothelial growth factor was performed
      on the glioma tissues from the 43 patients. Genomic DNA was extracted for
      bisulfate conversion and sequencing. SEMA3B was fully expressed in the three
      normal brain tissues, and incompletely expressed in the 43 glioma tissues, with a
      lack of expression in 48.8% (21/43) of samples. Moreover, 58% of high-grade
      gliomas (grade III and IV) lacked SEMA3B expression, which was significantly more
      than those that lacked expression (20%) in low-grade gliomas (grade I and II),
      indicating that, as the clinical pathological grade increased, SEMA3B expression
      decreased. The occurrence and development of malignant tumors is a product of
      multiple genes and other factors. Here, we provide theoretical basis for glioma
      development and prognosis involving DNA-methylation driven silencing of SEMA3B,
      and thus, SEMA3B is a potential target for directed treatments against glioma. 

PMID- 27050959
TI  - QTL mapping of soybean oil content for marker-assisted selection in plant
      breeding program.
AB  - The present study was undertaken to detect and map the quantitative trait loci
      (QTL) related to soybean oil content. We used 244 progenies derived from a bi
      parental cross of the Lineage 69 (from Universidade Estadual Paulista "Julio de
      Mesquita Filho"/Faculdade de Ciencias Agrarias e Veterinarias - Breeding Program)
      and Tucunare cultivar. A total of 358 simple sequence repeat (SSR;
      microsatellite) markers were used to investigate the polymorphism between the
      parental lines, and for the polymorphic lines all the F2 individuals were tested.
      Evaluation of the oil content and phenotype was performed with the aid of a Tango
      equipment by near infra-red reflectance spectroscopy, using single F2 seeds and
      F2:3 progenies, in triplicate. The data were analyzed by QTL Cartographer program
      for 56 SSR polymorphic markers. Two oil-content related QTLs were detected on K
      and H linkage groups. The total phenotypic variation explained by QTLs ranged
      from 7.8 to 46.75% for oil content. New QTLs were identified for the oil content
      in addition to those previously identified in other studies. The results reported
      in this study show that regions different from those already known could be
      involved in the genetic control of soybean oil content. 

PMID- 27050960
TI  - Cytogenetic findings in patients diagnosed with breast cancer having undergone
      adjuvant chemotherapy regimens.
AB  - The aim of the present study was to investigate DNA damage in peripheral blood
      lymphocytes of breast cancer (BC) patients before and after administration of
      chemotherapy. We analyzed the frequency of sister chromatid exchange (SCE),
      occurrence of micronuclei (MN), and lymphocyte proliferation rate index (PRI) as
      cytogenetic markers in 28 female BC patients before and after chemotherapy, and
      in 20 age-matched healthy female volunteers. Prior to treatment, BC patients
      showed significantly increased background levels of SCE and MN, and lowered PRIs
      compared to healthy women. In comparison with pre-treatment levels, SCE and MN
      frequencies were significantly elevated and PRI reduced in blood samples
      collected after chemotherapy. Our findings indicate that SCE, MN, and PRI may
      serve as sensitive biomarkers for routine detection of the genetic abnormalities
      that may occur following administration of antineoplastic drugs in the clinical
      setting, as well as for the monitoring of high-risk patients receiving
      chemotherapy for BC. 

PMID- 27050961
TI  - Cytotoxic and immunomodulatory effects of Ebenus boissieri Barbey on breast
      cancer cells.
AB  - We aimed to determine the cytotoxic and immunomodulatory effects of
      hydroalcoholic extracts of the roots and aerial parts of Ebenus boissieri (EB) on
      breast cancer MDA-MB231 cells and the non-cancerous human embryonic kidney cell
      line, 293T. Cell viability was determined by MTT assay, trypan blue exclusion,
      and Live/Dead Viability/Cytotoxicity assay. Apoptosis was evaluated by measuring
      the activity of caspase-2, 3, 6, 8, and 9. Tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-g release was assayed by ELISA, and protein expression of
      caspase-3, TNF-a, and IFN-g was determined by western blot. The results of this
      study revealed that MDA-MB231 cell viability was reduced in a dose-dependent
      manner by the aerial and root extract of EB at 72 h with a half-maximal
      inhibitory concentration (IC50) of 41.1 +/- 2.76 and 65 +/- 1.09 MUg/mL,
      respectively. In contrast, neither the aerial nor the root extracts of this plant
      inhibited the proliferation of 293T cells at doses up to 1000 MUg/mL. There was a
      time-dependent increase in caspase activity, especially caspase-3 and caspase-9.
      The levels of TNF-aand IFN-g significantly increased in MDA-MB231 cells treated
      with aerial extract. In conclusion, the extracts of EB induced apoptosis in
      breast cancer cells by altering the levels of caspases, TNF-a, and IFN-g. The
      components and precise modes of action of EB have not yet been determined.
      However, potential antitumor and immunomodulatory activity was observed along
      with selectivity against cancer cells in vitro, suggesting that hydroalcoholic
      extracts of this plant are worthy of additional study. 

PMID- 27050962
TI  - Role of IL-10 polymorphisms in susceptibility to hepatitis B virus-related
      hepatocellular carcinoma.
AB  - We conducted a case-control study to investigate the role of three common single
      nucleotide polymorphisms of IL-10 (-592G/A, -819T/C, and -1082A/C) in the
      development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
      The study included 173 HBV-related HCC patients and 182 healthy controls. A
      polymerase chain reaction-restriction fragment length polymorphism assay was
      applied to assess the sequence variants of interest. Compared with control
      subjects, HCC patients were more likely to be older (t = 1.94, P = 0.03), have a
      family history of cancer (chi square = 17.86, P < 0.001), and exhibit higher
      alanine transaminase (t = 13.32, P < 0.001) and aspartate transaminase (t =
      12.63, P < 0.001) levels. Using unconditional logistic regression analyses, we
      found that the GG genotype of -592G/A was associated with increased risk of HCC
      [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.12-4.38], compared to
      the AA genotype. Under a dominant model, the AG+GG genotype correlated with HBV
      related HCC susceptibility compared to the AA genotype, with an OR (95%CI) of
      1.56 (1.02-2.48). Moreover, a recessive model showed the GG genotype to be
      associated with elevated risk of HCC compared to the AA+AG genotype (OR = 1.85,
      95%CI = 1.01-3.47). However, no significant association between the -819T/C and 
      1082A/C variants and development of HBV-related HCC was observed under
      codominant, dominant, and recessive models. We conclude that the IL-10 -592G/A
      polymorphism does play a role in susceptibility to HBV-related HCC under
      codominant, dominant, and recessive models. 

PMID- 27050963
TI  - Genetic diversity in the germplasm of black pepper determined by EST-SSR markers.
AB  - This study aimed to assess genetic diversity in the germplasm of black pepper
      from around the world using SSR markers from EST. In total, 13 markers were
      selected and successfully amplified the target loci across the black pepper
      germplasm. All the EST-SSR markers showed high levels of polymorphisms with an
      average polymorphism information content of 0.93. The genetic similarity
      coefficients among all accessions ranged from 0.724 to 1.000, with an average of
      0.867. These results indicated that black pepper germplasms possess a complex
      genetic background and high genetic diversity. Based on a cluster analysis, 148
      black pepper germplasms were grouped in two major clades: the Neotropics and the
      Asian tropics. Peperomia pellucida was grouped separately and distantly from all
      other accessions. These results generally agreed with the genetic and geographic
      distances. However, the Asian tropics clade did not cluster according to their
      geographic origins. In addition, compared with the American accessions, the Asian
      wild accessions and cultivated accessions grouped together, indicating a close
      genetic relationship. This verified the origin of black pepper. The newly
      developed EST-SSRs are highly valuable resources for the conservation of black
      pepper germplasm diversity and for black pepper breeding. 

PMID- 27050964
TI  - Expression of Epstein-Barr virus antibodies EA-IgG, Rta-IgG, and VCA-IgA in
      nasopharyngeal carcinoma and their use in a combined diagnostic assay.
AB  - Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal
      carcinoma, which can be monitored by the levels of Rta protein antibody IgG (Rta
      IgG), early antigen antibody (EA-IgG), and viral capsid antibody (VCA-IgA). In
      the present study, we investigated the serum levels of Rta-IgG, EA-IgG, and VCA
      IgA in nasopharyngeal cancer patients, and the diagnostic value of a combined
      assay that includes these antibodies in addition to the EBV-DNA. A total of 56
      nasopharyngeal cancer patients were recruited as the study population, along with
      48 benign rhinitis patients and 42 healthy individuals. Serum EA-IgG, Rta-IgG,
      and VCA-IgA levels were measured by enzyme-linked immunosorbent assay, and EBV
      DNA was quantified with PCR. The diagnostic value of these indices was further
      evaluated by ROC curve analysis. The expression levels of EA-IgG, Rta-IgG, VCA
      IgA, and EBV-DNA were elevated in the nasopharyngeal cancer patients, who had
      higher levels of these antibodies than those in the rhinitis patients, followed
      by the healthy individuals. These indices were also increased with advanced TNM
      stage. The overall diagnostic efficacy was ranked as follows: VCA-IgA, Rta-IgA,
      EA-IgA, and EBV-DNA. The combined diagnosis using these four indices increased
      the sensitivity to 98.21% and the negative predictive value to 98.61%, without
      any significant compromise on the test specificity. In conclusion, EA-IgG, Rta
      IgG, VCA-IgA, and EBV-DNA expression levels were elevated in nasopharyngeal
      patients. The combined diagnostic value of these serum indices has important
      implications in nasopharyngeal carcinoma. 

PMID- 27050965
TI  - Analysis of correlations between coronary heart disease and haplotypes of the
      angiotensin II receptor type 1 (AGTR1) gene.
AB  - This study aimed to explore correlations between haplotypes of the angiotensin II
      receptor type 1 (AGTR1) gene and coronary heart disease (CHD). In total, 204
      patients with CHD and 206 healthy controls were genotyped using denaturing high
      performance liquid chromatography between 2008 and 2014. Five polymorphic loci
      were found, namely, A-43281G, A-32954G, G-32839A, G-11064A, and A1880G.
      Likelihood estimates were used to identify haplotypes consisting of the A1166C
      locus and four of these five loci, then correlations between these haplotypes and
      CHD were assessed. Eight haplotypes with a frequency greater than 3% in the study
      population were discerned: ACCAA [odds ratio (OR) = 1.2381, 95% confidence
      interval (CI) = 0.7726-1.9843]; ACCCA (OR = 1.2604, 95%CI = 0.6104-2.6027); ACTAA
      (OR = 0.8929, 95%CI = 0.6607-1.2067); ACTAG (OR = 0.9274, 95%CI = 0.5692-1.5110);
      ATTAA (OR = 1.0347, 95%CI = 0.7505-1.4265); ATTAG (OR = 0.9110, 95%CI = 0.4227
      1.9631); GCCAA (OR = 1.1273, 95%CI = 0.7259-1.7506); and GCTAA (OR = 0.7981,
      95%CI = 0.4379-1.4546). However, the frequency of these haplotypes did not
      significantly differ between CHD and the control groups. Thus, no correlation was
      established between the occurrence of CHD and AGTR1 haplotypes present at
      frequencies greater than 3%. 

PMID- 27050966
TI  - Isolation and characterization of novel microsatellite markers in Mercenaria
      mercenaria.
AB  - Mercenaria mercenaria, also known as the hard clam, is widely distributed in the
      coastal waters of temperate and tropical areas in the Asian Pacific region. This
      species is widely popular in the international market, especially in the United
      States, Europe, and other Western countries, because of its high protein value,
      taste, and simple farming requirements. In this study, 17 novel microsatellite
      loci from the M. mercenaria genome were developed using the fast isolation by
      amplified fragment length polymorphism of sequences containing repeats protocol.
      Thirty-two wild individuals were used to evaluate the degree of polymorphism of
      these markers. Results indicated that there were 11 polymorphic loci and six
      monomorphic loci, and the number of alleles per locus and the polymorphism
      information content ranged from two to six and from 0.059 to 0.498, respectively.
      The observed and expected heterozygosity varied from 0.0625 to 0.5333 and 0.0615
      to 0.4977, respectively. The Y1-4 locus deviated significantly from Hardy
      Weinberg equilibrium (HWE) after Bonferroni correction was applied, while the
      other loci were in HWE. These loci will provide useful information for M.
      mercenaria population genetic studies. 

PMID- 27050967
TI  - All-trans retinoic acid prevents the development of type 1 diabetes by affecting
      the levels of interferon gamma and interleukin 4 in streptozotocin-induced murine
      diabetes model.
AB  - The aim of this study was to explore the molecular mechanism by which all-trans
      retinoic acid (ATRA) prevents type 1 diabetes mellitus (T1DM). Fifty ICR mice
      were randomly assigned to three groups: prevention group [N = 20; mice received
      10 mg/kg ATRA daily for 5 days and then 60 mg/kg streptozotocin (STZ) for 5
      days]; diabetic group (N = 20, mice received 95% sterile peanut oil and 5%
      dimethyl sulfoxide for 5 days and then 60 mg/kg STZ for 5 days); and control
      group (N = 10, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for
      5 days and then citrate buffer for 5 days). Blood glucose was measured using
      blood glucose test strips and serum insulin was measured by radioimmunoassay.
      Islets cell morphology was assessed by microscopy and ELISA was used to measure
      the serum levels of interferon gamma (IFN-gamma) and interleukin 4 (IL- 4). In
      the prevention group, blood sugar levels were found to be reduced and serum
      insulin levels increased compared with the levels in the diabetic group (P <
      0.05), indicating that ATRA prevented the STZ-induced damage to islet cells.
      Meanwhile, ATRA was shown to decrease the levels of IFN-gamma and increase the
      levels of IL-4 as well as the IFN-gamma/IL-4 ratio in STZ-treated animals (P <
      0.05). These findings suggest that ATRA prevents the recurrence of autoimmune
      insulitis. This study demonstrated that ATRA effectively prevents the progression
      of T1DM in a murine model of the disease by reducing IFN-gamma levels and
      increasing IL-4 levels. 

PMID- 27050968
TI  - Cytochemical characteristics of blood cells from Brazilian tortoises (Testudines:
      Testudinidae).
AB  - The hematology of wild and captive animals is essential for obtaining details
      about species and represents a simple method of diagnosing disease and
      determining prognosis. Few studies have described the morphology of chelonian
      blood cells, which are more common in sea and freshwater turtle species. Thus, in
      order to further our understanding and recognition of different chelonian cells
      types, the present study aimed to describe blood cells from the two species of
      Brazilian tortoises, Chelonoidis carbonarius and C. denticulatus. Cytochemical
      analysis of tortoise blood tissue with Panotico(r), made it possible to describe
      all the of the chelonian cell types (with the exception of thrombocytes):
      erythrocytes, agranular leukocytes (monocytes and lymphocytes), and granular
      leukocytes (eosinophils, heterophils, basophils, and azurophils). These data are
      of high importance for establishing hematological profiles of Brazilian tortoises
      and reptiles. Therefore, based on our results and on comparative analyses with
      data from the literature for other reptile species, we can conclude that the
      blood cells described for Brazilian tortoises are found in all species of
      reptiles that have been analyzed thus far, and may be characterized and used as a
      comparative parameter between different groups to evaluate the health status of
      these animals. 

PMID- 27050969
TI  - A 425 T>C polymorphism in complement C7 association with resistance to Aeromonas
      hydrophila in grass carp.
AB  - Aeromonas hydrophila, a widespread bacterium in the aquatic environment, causes
      hemorrhagic septicemia in fish. In the last decade, the disease has caused mass
      mortalities and tremendous economic loss in cultured fish. The complement
      component C7 is a terminal component of complement that interacts in a sequence
      of polymerization reactions with other terminal complement components to form a
      membrane attack complex. The formation of the membrane attack complex creates a
      pore in the membranes of certain pathogen that can lead to their death. The
      objective of this study was to identify single nucleotide polymorphisms (SNPs) in
      the C7 gene and to assess their association with A. hydrophila resistance in
      grass carp. A resource population consisting of 186 susceptible and 191 resistant
      grass carp was constructed. We sequenced a total of 7826 bp of the C7 gene and
      identified 6 SNPs that were genotyped in the resource population. The SNP -1575
      A>C was positioned in the promoter region of the gene. The SNP 425 C>T identified
      in the coding exon was a synonymous substitution in the fourth exon. Statistical
      analysis showed that SNP 425 C>T was associated with the incidence of hemorrhagic
      septicemia. The SNPs -1575 A>C, -688 T>C, and -266 A>C were highly linked
      together (r(2) > 0.85). No haplotypes generated with these 3 SNPs were associated
      with resistance to A. hydrophila in grass carp. These findings suggest that the
      425 C>T polymorphism in C7 gene may be a significant molecular marker for
      resistance to A. hydrophila in grass carp. 

PMID- 27050970
TI  - Association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical
      cancer risk in a Chinese population.
AB  - The association of the programmed cell death-1 PD1.5 C>T polymorphism with
      cervical cancer risk has not been investigated. In this hospital-based case
      control study, we analyzed 256 patients with cervical cancer and 250 healthy
      controls. Pearson chi-square test was used to examine differences in the
      distribution of genotypes between cases and controls. Association between the
      polymorphism and the susceptibility to cervical cancer was evaluated using
      unconditional logistic regression analysis. This revealed that the frequencies of
      the three genotypes (CC, CT, and TT) in cervical cancer cases and controls were
      17.58, 65.23, and 17.19% and 24.80, 40.40, and 34.80%, respectively; the
      difference between the two groups was significant (P < 0.001). We found that the
      CT genotype was significantly associated with increased cervical cancer risk
      (adjusted OR = 2.18; 95%CI = 1.37-6.11; P = 0.009). Moreover, there was
      significant association between PD-1.5 C/T polymorphism and susceptibility to
      cervical cancer under dominant model (OR = 1.27, 95%CI = 1.01-2.15, P = 0.047).
      We conclude that the PD-1.5 C/T polymorphism may be associated with increased
      risk of cervical cancer. The study also highlights the importance of conducting
      genetic association studies in different ethnic populations. 

PMID- 27050971
TI  - Effect of atmospheric fine particles on epidermal growth factor receptor mRNA
      expression in mouse skin tissue.
AB  - We investigated the effect of atmospheric fine particles on epidermal growth
      factor receptor (Egfr) mRNA expression in mouse skin tissue and explored the
      effect of atmospheric fine particles on skin aging. Forty female BALB/c mice were
      randomly divided into four groups (each comprising 10 mice) as follows: a saline
      control group and low-, medium-, and high-dose atmospheric fine particle groups
      (1.6, 8.0, and 40.0 mg/kg, respectively) (fine particles were defined as those
      with a diameter of L2.5 mm, i.e., PM2.5). Each dose group was exposed to
      intratracheal instillation for 3 days. Twenty-four hours after the last exposure,
      real-time quantitative polymerase chain reaction was used to detect the
      expression of Egfr mRNA in the skin tissue of each mouse. The expression levels
      of Egfr mRNA in the medium- and high-dose PM2.5 groups were significantly higher
      (P < 0.05) than that in the control group, and were positively correlated with
      the dose. Medium and high concentrations of PM2.5 can induce the expression of
      Egfr mRNA and promote skin aging. 

PMID- 27050972
TI  - Effects of tail docking on the expression of genes related to lipid metabolism in
      Lanzhou fat-tailed sheep.
AB  - To evaluate stearoyl-CoA desaturase (SCD), hormone-sensitive lipase (HSL),
      lipoprotein lipase (LPL), and peroxisome proliferator-activated receptor
      (PPARgamma) expression in Lanzhou fat-tailed sheep (with and without docked
      tails), 18 rams were randomly divided into two equal groups (docked group, LT;
      control group, LC). These data were also used to increase the understanding of
      sheep fat deposition and metabolism. All animals were harvested at the age of 18
      months, and expression was determined for 10 tissues. The results indicated that
      the fat weight of each tissue in LT was higher than in LC (P < 0.05). SCD
      expression in semitendinosus, omentum majus fat (OF), subcutaneous fat, kidney
      fat (KF), and subcutaneous rump fat was higher in LT than in LC rams (P < 0.05).
      Trends (P < 0.10) associated with higher HSL expression of LC in comparison to
      that of LT rams in intestinal fat, OF, and KF tissues were detected. Numerically,
      LPL expression was the highest in KF, OF, and kidney tissues, but there were few
      differences (P > 0.10). PPARgammaexpression was greater in LT than in LC rams in
      liver tissues (P < 0.05), but there were few differences in other tissues. No
      significant differences were found with regard to the regression analysis of
      expression and adipose tissue weights, but the two indices exhibited the same
      trend. The results indicated that changes in fatty deposits may be due to the
      common control of docking management and the minor effects associated with the
      regulation of SCD, HSL, LPL, and PPARgammaexpression. 

PMID- 27050973
TI  - Relationship between the expression of Notch1 and EZH2 and the prognosis of
      breast invasive ductal carcinoma.
AB  - We determined whether the coexpression of Notch1 and EZH2 influences the
      progression and prognosis of breast invasive ductal carcinoma. Using the chi(2)
      test, a significant difference was found between high and low expression of
      Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05).
      Moreover, a significant difference was found between high and low expression of
      EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression
      of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant
      positive correlation between Notch1 and EZH2 expression in the tissue samples of
      breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was
      associated with poor progression-free survival compared with low expression
      (PNotch1 = 0.000, 40.3 vs 48.9 months; PEZH2 = 0.000, 40.2 vs 49.9 months).
      Moreover, we found that high Notch1 and EZH2 expression was associated with poor
      overall survival compared with low expression (PNotch1 = 0.000, 51.2 vs 56.2
      months; PEZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2
      coexpression contributes to the progression and prognosis of breast invasive
      ductal carcinoma. 

PMID- 27050974
TI  - A fast and simple method for the polymerase chain reaction-based sexing of
      livestock embryos.
AB  - Embryo sexing is a powerful tool for livestock producers because it allows them
      to manage their breeding stocks more effectively. However, the cost of supplies
      and reagents, and the need for trained professionals to biopsy embryos by
      micromanipulation restrict the worldwide use of the technology to a limited
      number of specialized groups. The aim of this study was to couple a fast and
      inexpensive DNA extraction protocol with a practical biopsy approach to create a
      simple, quick, effective, and dependable embryo sexing procedure. From a total of
      1847 sheep and cattle whole embryos or embryo biopsies, the sexing efficiency was
      100% for embryo biopsies, 98% for sheep embryos, and 90.2% for cattle embryos. We
      used a primer pair that was common to both species and only 10% of the total
      extracted DNA. The whole protocol takes only 2 h to perform, which suggests that
      the proposed procedure can be readily applied to field conditions. Moreover, in
      addition to embryo sexing, the procedure can be used for further analyses, such
      as genotyping and molecular diagnosis in preimplantation embryos. 

PMID- 27050975
TI  - Significance of TNF-alpha and IL-6 expression in invasive pituitary adenomas.
AB  - The aim of this study was to investigate expression of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) in invasive pituitary adenomas (IPAs).
      The streptavidin peroxidase immunohistochemical method was employed to detect
      their expression in 40 cases of IPA and 40 of non-invasive pituitary adenoma
      (NIPA). TNF-alpha and IL-6 were found to be upregulated in IPA tissue compared
      with that of NIPA (P < 0.05). These proteins may therefore play important roles
      in the occurrence and progression of IPA. 

PMID- 27050976
TI  - Sperm quality and DNA damage in men from Jilin Province, China, who are
      occupationally exposed to ionizing radiation.
AB  - Long-term radiation exposure affects human health. Ionizing radiation has long
      been known to raise the risk of cancer. In addition to high doses of radiation,
      low-dose ionizing radiation might increase the risk of cardiovascular disease,
      lens opacity, and some other non-cancerous diseases. Low- and high-dose exposures
      to ionizing radiation elicit different signaling events at the molecular level,
      and may involve different response mechanisms. The health risks arising from
      exposure to low doses of ionizing radiation should be re-evaluated. Health
      workers exposed to ionizing radiation experience low-dose radiation and have an
      increased risk of hematological malignancies. Reproductive function is sensitive
      to changes in the physical environment, including ionizing radiation. However,
      data is scarce regarding the association between occupational radiation exposure
      and risk to human fertility. Sperm DNA integrity is a functional parameter of
      male fertility evaluation. Hence, we aimed to report sperm quality and DNA damage
      in men from Jilin Province, China, who were occupationally exposed to ionizing
      radiation. Sperm motility and normal morphology were significantly lower in the
      exposed compared with the non-exposed men. There was no statistically significant
      difference in sperm concentration between exposed and non-exposed men. The sperm
      DNA fragmentation index was significantly higher in the exposed than the non
      exposed men. Chronic long-term exposure to low doses of ionizing radiation could
      affect sperm motility, normal morphology, and the sperm DNA fragmentation index
      in the Chinese population. Sperm quality and DNA integrity are functional
      parameters that could be used to evaluate occupational exposure to ionizing
      radiation. 

PMID- 27050977
TI  - Letter to the Editor Reply to commentary by G. Sikri and S. Dua on the article
      "Correlation between single nucleotide polymorphisms in hypoxia-related genes and
      susceptibility to acute high-altitude pulmonary edema" published in Genetics and
      Molecular Research 14 (3): 11562-11572 to the letter published in Genet. Mol.
      Res. 14 (4): 15904-15905.
AB  - The object in this study was a Han Chinese population in Lhasa, with 3658 m in
      altitude from Chengdu, which has 505 m in altitude by air. Within 24 to 48 h
      before the subjects arrived in the plateau, they completed a basic situation
      questionnaire, under the guidance of medical staff. Within 24 to 48 h after they
      reached the plateau, the subjects completed an acute plateau disease
      questionnaire. The diagnostic standard of HAPE and the diagnosis of acute plateau
      disease were adopted by the Lake Louise diagnostic standards in 1991 and the
      Chinese Medical Association promulgated the domestic diagnostic criteria on the
      Third National Plateau Medical Academic Seminar. Other diseases that cause acute
      symptoms of altitude sickness, such as plateau pulmonary edema, plateau cerebral
      edema, acute respiratory infections and neurosis, were excluded. According to the
      Lake Louise standard, questionnaire and symptom score values >3 points were
      diagnosed as HAPE. According to the national standard, the questionnaire and
      symptom score values >5 points were diagnosed as HAPE. At the present, morbidity
      of HAPE remains relatively high in China. The research shows that usually in the
      case of not taking preventive measures, according to the factors such as
      altitude, speed, and time of arrival, the incidence of HAPE is 30% to 90%.
      Epidemiological survey shows that HAPE happens at an altitude of 2500 m above the
      plateau. And an altitude of 3000 m above the plateau of China is occupied 1/6 of
      the total land area, the population of permanent residents is more than sixty
      million. We detected the 200 cases who adapted to plateau and the 106 cases of
      patients with HAPE susceptibility genes SNP locus, and got the key SNP loci of
      HAPE susceptibility genes. We maked the corresponding gene chip diagnostic kits. 

PMID- 27050978
TI  - Correlation between serum IL-16 and atopic dermatitis.
AB  - This study aims to investigate the correlation between allergic sensitization of
      atopic dermatitis (AD) patients and their serum interleukin (IL)-16 levels. AD
      patients, healthy volunteers, and patients with psoriasis (N = 80, 35, 20,
      respectively) were tested for serum IL-16 and total and specific IgE levels by
      enzyme-linked immunosorbent assay, along with eosinophil counts. Serum allergen
      specific IgE levels were determined, and skin-prick testing conducted in a
      subgroup of 45 AD patients. Based on specific IgE levels, AD patients were
      categorized into non-sensitized group 1 and sensitized group 2. Furthermore, they
      were sorted as non-sensitized group A and sensitized group B based on skin-prick
      results. Next, the serum IL-16 and total IgE levels in these subgroups were
      determined. Compared to levels in healthy volunteers and psoriasis patients, the
      serum IL-16 levels in AD patients were significantly higher (P < 0.001).
      Additionally, total serum IgE levels were significantly correlated with serum IL
      16 levels and eosinophil counts. However, no correlation was observed between
      serum IL-16 levels and eosinophil counts. The serum IL-16 and total IgE levels in
      group 2 were also significantly elevated (P < 0.001) in contrast to those in
      group 1. Although we did not observe any significant difference between serum IL
      16 levels in groups A and B, the total serum IgE level in group B was
      significantly higher than that in group A (P < 0.001). Thus, allergic sensitivity
      in AD patients correlates with total serum IgE as well as serum IL-16; the
      correlation with IL-6 is weaker. 

PMID- 27050979
TI  - Polymorphisms in promoter regions of IL-6 and IL-10 genes in breast cancer: a
      case-control study.
AB  - Polymorphisms in interleukin genes (IL-6 and IL-10) are involved in the
      pathogenesis of breast cancer. This study investigated polymorphisms in the
      promoter regions of IL-6 (-174G/C) and IL-10 (-1082G/A) through a case-control
      study employing 80 female subjects who were pathologically diagnosed with breast
      cancer. All patients received follow-up care at the Mansoura University Hospital,
      Mansoura, Egypt. We included another 80 females (controls) from the same
      population, showing no signs of malignancy. Clinicopathological features were
      examined in the patient groups, including the expression of estrogen and
      progesterone receptors, involvement of the lymph node, tumor morphology, and
      tumor grades. Genotyping of the promoter polymorphisms was performed using allele
      specific polymerase chain reaction method. There was a significant decrease in
      the mean age of menarche in the patient group than that in the normal
      individuals. For the IL-6 -174G/C polymorphism, there was a significantly higher
      frequency of the CC genotype in the patients than that in the controls (odds
      ratio = 5.49). Furthermore, the CC genotype was significantly more prevalent
      among the patients who had lymph node involvement. For the IL-10 -1082G/A
      polymorphism, there was no difference in the distribution of genotypes among the
      patients and the control subjects. However, the tumor size was significantly
      larger in patients who were harboring the AA genotype than that in the patients
      who had AG or GG genotypes. 

PMID- 27050980
TI  - Spermiotaxonomy of the tribe Rhodniini (Hemiptera, Triatominae).
AB  - The tribe Rhodniini is a monophyletic group composed of 22 species, with 19 in
      the Rhodnius genus and three in the Psammolestes genus. These insects are
      morphologically very similar (cryptic species), and new tools are important for
      investigating the taxonomy of these vectors. Spermiotaxonomy is an important tool
      in differentiating between related species, and this study analyzed the
      spermatids of Rhodniini species to elucidate their spermiotaxonomy. All of the
      Rhodniini species contained two heteropyknotic filaments in the extremities of
      their cells. Although spermiotaxonomy has been an important tool in
      differentiating between species of the Triatoma genus, all of the species in the
      Rhodnius genus exhibited the same characteristics in their male gametes. However,
      spermatid analysis made it possible to confirm the monophyly of the Rhodniini
      tribe, because Psammolestes tertius had the same pattern as that described for
      Rhodnius. The results of this study demonstrate that spermiotaxonomy, in addition
      to being an important tool for differentiating between related species of
      Triatoma, can be used as an optimization tool in phylogenetic analyses. 

PMID- 27050981
TI  - Diversity and genetic parameter estimates for yield and its components in
      Jatropha curcas L.
AB  - Jatropha curcas L. is one of the most promising oilseeds for biodiesel and
      biokerosene production, but few basic studies or breeding programs have been
      conducted for the species. We estimated genetic parameters and diversity based on
      10 yield traits in 77 half-sib progenies of J. curcas after 52 months in the
      field, and evaluated correlations between them and the oil content of the seeds.
      The mean grain yield per plant was 377.9 g (ranging from 169.8 to 772.1 g) and
      the mean oil content was 36.2% (ranging from 30 to 39.6%). Moderate estimates of
      heritability at the mean progeny level were obtained for the length of the fruit
      (84.7%), length (69.1%) and width (68.2%) of the seed, and grain yield per plant
      (62.2%). Oil content was only positively and significantly correlated with 100
      seed weight. Our study revealed a range of possible crosses to be investigated in
      J. curcas. Progeny production should be evaluated over several crop seasons for
      the accurate selection of the best progenies. 

PMID- 27050982
TI  - Roles of oxidative DNA damage of bone marrow hematopoietic cells in steroid
      induced avascular necrosis of femoral head.
AB  - An animal model of steroid-induced avascular necrosis of femoral head (SANFH) was
      established to investigate the role of oxidative DNA damage of bone marrow
      hematopoietic cells in SANFH. Forty-five-month-old Japanese white rabbits (male
      or female, 2.5 +/- 0.5 kg) were randomly divided into groups A
      (methylprednisolone + Escherichia coli endotoxin), B (methylprednisolone alone),
      C (E. coli endotoxin alone), and D (blank control). The animals were sacrificed
      two and four weeks after administration of the last dose (N = 5 each group and
      each time). Left and right femoral heads were fixed and decalcified. Empty
      lacunae were counted by hematoxylin and eosin staining and oxidative DNA damage
      of bone marrow hematopoietic cells was detected by immunohistochemistry. At week
      2, the rate of oxidative DNA damage in bone marrow hematopoietic cells was
      significantly higher in group A than in groups B, C, and D (P < 0.01), while
      there was no significant difference between groups B, C, and D. At week 4, the
      rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly
      higher in group A than in groups B, C, and D (P < 0.01), while there was no
      significant difference among groups B, C, and D. Thus, oxidative DNA damage of
      bone marrow hematopoietic cells appears to play an important role in SANFH. 

PMID- 27050983
TI  - Repellent effects of various cherry tomato accessions on the two-spotted spider
      mite Tetranychus urticae Koch (Acari: Tetranychidae).
AB  - Several studies have been conducted on resistance sources to improve the genetic
      resistance of farm-grown tomatoes to arthropod pests, including phytophagous
      mites. In the present study, we evaluate the behavior of the two-spotted spider
      mite on different cherry tomato accessions to identify possible sources of
      resistance (repellent effect) to this pest. Sixty-four accessions of cherry
      tomatoes, Solanum lycopersicum var. cerasiforme (Dunal), were tested. In
      addition, a commercial cultivar of cherry tomato cv. Sweet Grape (susceptible
      pattern) and the wild tomato accession Solanum pennellii Correll LA-716 (multiple
      pest resistance) were evaluated as well. The distance traveled by mites on the
      leaflet surface over time varied largely among cherry tomato accessions. The wild
      genotype, S. pennellii LA-716, showed the smallest traveled distance on the
      leaflet surface (0.8 to 1.1 mm over time), and the variety cv. Sweet Grape was
      one of the genotypes with highest traveled distance (16.2 to 16.4 mm over time).
      The cherry tomato accessions 2298-42, RVTC-03, and 6889-53 showed a decrease in
      the traveled distance by mites over time, similar to that as observed in the wild
      tomato accession LA716. These accessions showed mite repellence levels similar to
      those of the wild genotype and may, therefore, be good candidates for breeding
      programs dealing with resistance to mites. 

PMID- 27050984
TI  - Immune function of nonparenchymal liver cells.
AB  - The liver is the human body largest digestive and metabolic organ, and a very
      important immune organ. This paper discusses the location and morphology of
      hepatic sinusoidal endothelial cells, dendritic cells, hepatic stellate cells,
      and Kupffer cells in the liver and their role in regulating immune functions.
      Therefore, here we provide a preliminary understanding of the immune regulatory
      function of liver cells, and information on the occurrence and treatment of liver
      diseases. 

PMID- 27050985
TI  - Acrocomia emensis (Arecaceae) genetic structure and diversity using SSR molecular
      markers.
AB  - Acrocomia emensis, popularly known as the creeping tucum, belongs to the family
      Arecaceae, and is an oilseed specie of the Brazilian Savannah. The expansion of
      agricultural activity has rapidly destroyed its natural habitat, leading to a
      decrease in its population size. Genetic studies can be used to investigate the
      genetic variability, and may assist with the charting future conservation
      strategies. In this study the genetic diversity and structure of 150 individuals
      sampled in three locations in Minas Gerais were analysed, based on the
      transferability of six microsatellite markers, previously developed for A.
      aculeata. The results indicate that the populations studied have low levels of
      genetic variability (Ho = 0.148) and high, positive and significant inbreeding
      coefficient, indicating an excess of homozygotes. The average heterozygosity
      within the population (Hs = 0.700) accounted for 95.03% of the total genetic
      diversity, indicating that there is greater variability within population than
      between them, consistent with low genetic differentiation between population (GST
      = 0.046). Bayesian analysis identified three distinct groups; however,
      populations shared large numbers of alleles, which can be explained by the
      reduced distance between populations. These results reveal the need to implement
      genetic conservation programs for the maintenance of this species and to
      prioritize population from Bonito and Brasilia, which showed the lowest values of
      genetic diversity. 

PMID- 27050986
TI  - WNT10A polymorphism may be a risk factor for non-syndromic hypodontia.
AB  - This study was designed to determine whether polymorphisms in the gene wingless
      type MMTV integration site family, member 10A (WNT10A) are associated with non
      syndromic hypodontia (tooth agenesis). A case-control study was performed
      involving 129 subjects with sporadic non-syndromic hypodontia (cases) and 218
      healthy individuals (controls). DNA was obtained from whole blood and the ligase
      detection reaction method was used to analyze two single nucleotide polymorphisms
      (SNPs) of the WNT10A gene. A significant difference between cases and controls
      was observed in the allele and genotype frequencies of both SNPs (rs116998555 and
      rs147680216). For rs116998555, the presence of the T allele (the thymine variant)
      was associated with tooth agenesis [odds ratio (OR) = 5.722; 95% confidence
      interval (CI) = 3.053-10.727; P < 0.001], while for rs147680216, the A allele
      (the adenine variant) correlated with this condition (OR = 2.665; 95%CI = 1.512
      4.695; P < 0.001). We provide here the first case-control study evidence that
      risk of hypodontia may be related to the WNT10A polymorphism. Our results also
      confirm the importance of the Wnt pathway in tooth development. 

PMID- 27050987
TI  - Interleukin-17 enhances the removal of respiratory syncytial virus in mice by
      promoting neutrophil migration and reducing interferon-gamma expression.
AB  - The aim of this study was to observe the effect of interleukin (IL)-17 on early
      immune response and inflammation in the lungs of respiratory syncytial virus
      (RSV)-infected mice. Specific pathogen-free BALB/c mice were randomly assigned to
      control, RSV-infected, RSV-infected with phosphate-buffered saline, and RSV
      infected + IL-17 intervention groups. The RSV infection model was set up by nasal
      mucosa immunization. The intervention group was provided with restructured IL-17
      (intranasal). The viral load and cytokine concentrations in the lung tissues and
      broncho-alveolar lavage fluid (BALF) were determined by real-time-polymerase
      chain reaction and enzyme-linked immunosorbent assay. RSV caused acute lung
      inflammation in mice with a significantly higher number of neutrophils and
      cytokines such as interferon-gamma (IFN-gamma), IL-1beta, IL-6, and G-CSF in the
      BALF than that in the control group. IL-17 intervention led to a significant
      increase in the number of neutrophilic granulocytes in the BALF. Alternately, IL
      17 intervention led to a significant decrease in the IFN-gamma concentration and
      a significant increase in the IL-1beta, IL-6 and G-CSF levels in the BALF. IL-17
      induced a reduction in the viral load and an increase in the survival rate of
      mice on the third day of infection. IL- 17 mucosal immunity enhances the removal
      of RSV and strengthens the immune defense by promoting neutrophil migration and
      reducing the IFN-gamma levels in mouse lungs. 

PMID- 27050988
TI  - Branches of the NF-kappaB signaling pathway regulate proliferation of oval cells
      in rat liver regeneration.
AB  - The NF-kB (nuclear factor kB) pathway is involved in the proliferation of many
      cell types. To explore the mechanism of the NF-kB signaling pathway underlying
      the oval cell proliferation during rat liver regeneration, the Rat Genome 230 2.0
      Array was used to detect expression changes of NF-kB signaling pathway-related
      genes in oval cells. The results revealed that the expression levels of many
      genes in the NF-kB pathway were significantly changed. This included 48 known
      genes and 16 homologous genes, as well as 370 genes and 85 homologous genes
      related to cell proliferation. To further understand the biological significance
      of these changes, an expression profile function was used to analyze the
      potential biological processes. The results showed that the NF-kB pathway
      promoted oval cell proliferation mainly through three signaling branches; the
      tumor necrosis factor alpha branch (TNF-a pathway), the growth factor branch, and
      the chemokine branch. An integrated statistics method was used to define the key
      genes in the NF-kB pathway. Seven genes were identified to play vital roles in
      the NF-kB pathway. To confirm these results, the protein content, including two
      key genes (TNF and FGF11) and two non-key genes (CCL2 and TNFRSF12A), were
      analyzed using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass
      spectrometry. The results were generally consistent with those of the array data.
      To conclude, three branches and seven key genes were involved in the NF-kB
      signaling pathway that regulates oval cell proliferation during rat liver
      regeneration. 

PMID- 27050989
TI  - Population structure of jatropha and its implication for the breeding program.
AB  - Jatropha (Jatropha curcas L.) has potential as an oilseed crop that requires the
      development of technology for its exploitation. The objective of this study was
      to assess the population structure and the genetic diversity in jatropha
      accessions at a global level using simple sequence repeat (SSR) molecular
      markers. Jatropha accessions (N = 109) from 10 countries were genotyped using 10
      SSR markers. The results showed a low level of genetic diversity among 92
      accessions originating from India, Mozambique, Ethiopia, Tanzania, Brazil,
      Honduras, and Indonesia, which were grouped in one cluster. In contrast,
      accessions from Mexico and Costa Rica showed high level of genetic variability.
      These accessions may be used to increase the genetic diversity of jatropha in the
      breeding populations. The study also showed the need of collecting activity from
      the center of diversity (Mexico and Costa Rica) to aggregate the genetic
      diversity in the international collections of jatropha. 

PMID- 27050990
TI  - Mitochondrial dysfunction in resveratrol-induced apoptosis in QGY-7701 cells.
AB  - This study aims to evaluate the cytotoxicity of resveratrol on QGY-7701 cells via
      a cell viability assay, and determine the cytological alterations and damages
      that result. Resveratrol was found to inhibit QGY-7701 cell growth and decrease
      their viability in a remarkably dose-dependent manner. Resveratrol exposure also
      induced an increase in Caspase-3 activity and a decrease in Bcl-2, which caused
      an increase in membrane permeability, and the opening of mitochondrial
      permeability transition pores and mitochondrial depolarization. Cellular ATP is
      thus exhausted, and apoptosis is induced via the change in mitochondrial membrane
      permeability and mitochondrial dysfunction. 

PMID- 27050991
TI  - Isolation and characterization of new microsatellite loci in Fenneropenaeus
      penicillatus.
AB  - Fenneropenaeus penicillatus is one of the major economic shrimp species in China.
      In this study, 14 novel microsatellite loci were developed using the fast
      isolation protocol with amplified fragment length polymorphism of sequences
      containing repeats (FIASCO). Polymorphisms were tested in 30 individuals from a
      single-wild population. The results showed that the number of alleles at each
      locus ranged from two to four, and the polymorphism information content varied
      from 0.314 to 0.692. The observed and expected heterozygosities ranged from
      0.3343 to 0.6542 and from 0.3458 to 0.6657, respectively. Three loci deviated
      significantly from Hardy-Weinberg equilibrium after a Bonferroni correction was
      applied, while no deviations were detected in the other 11 loci. The new
      microsatellite loci identified in this study could be useful in future F.
      penicillatus population genetic, conservation research, population structure
      assessment, and linkage map construction studies. 

PMID- 27050992
TI  - miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating
      FOXC1 expression.
AB  - Many studies have shown that microRNA (miR)-133 functions as a tumor suppressor
      in a variety of metastatic cancers, including breast cancer, gastric cancer, and
      liver fibrosis. However, the influence of miR-133 on pituitary tumor malignancy
      has not yet been reported. The purpose of this study was to explore the role of
      miR-133 in pituitary tumor cell migration and invasive ability and the molecular
      mechanisms involved. Our findings suggest that in pituitary adenoma cell lines,
      through direct targeting and negative control of forkhead box C1 (FOXC1), miR-133
      can inhibit pituitary adenoma cell migration and invasion. In addition,
      epithelial-to-mesenchymal transition can be induced by miR-133. Additionally, a
      negative correlation was found between FOXC1 and miR-133 expression when
      comparing their expression levels between cancerous tissue and adjacent normal
      tissue. This suggests that miR-133 can inhibit cell migration and invasion by
      directly targeting FOXC1, implying that miR-133 could be a potential therapeutic
      target for treatment of invasive pituitary adenoma. 

PMID- 27050993
TI  - Protective effect of the n-butanol Toona sinensis seed extract on diabetic
      nephropathy rat kidneys.
AB  - The objective of this study was to observe the protective effect of the n-butyl
      alcohol phase of Toona sinensis seed extract on the kidneys of diabetic
      nephropathy (DN) rats and its preliminary mechanism. Male wistar rats were
      administered a normal or high-fat diet for 1 month. DN rats were divided into a
      model group and a petroleum ether phase of T. sinensis seed extract intervention
      group. The intervention group was administered 5 mg.100 g-1.day-1 extract. After
      treatment for 10 weeks, the rats were sacrificed and blood samples and the renal
      cortex were collected. Biochemical indicators in the serum and renal indices were
      assessed. Pathological changes of the renal tissues were also determined. Changes
      in the renal structure and protein levels were detected. Compared with the normal
      group, the blood glucose, urinary albumin, renal index, and oxidative stress
      index were sharply increased in the model group. The protein levels of TGF-b1,
      collagen IV, and connective tissue growth factor (CTGF) were increased. Compared
      with the model group, the n-butyl alcohol phase of T. sinensis seed extract
      significantly reduced the blood glucose, urinary albumin, renal index, oxidative
      stress index, serum creatinine, and urea nitrogen levels. The renal pathology
      abnormality was improved in DN rats. The protein levels of TGF-b1, collagen IV,
      and CTGF were increased. The expression of TGF-b1, collagen IV, and CTGF
      decreased. In conclusion, the n-butyl alcohol phase of T. sinensis seed extract
      has protective effects on DN rats via the inhibition of oxidative stress and
      protein expression of TGF-b1, collagen IV, and CTGF. 

PMID- 27050994
TI  - Effects of Sirtuin 1 on the proliferation and osteoblastic differentiation of
      periodontal ligament stem cells and stem cells from apical papilla.
AB  - The function of SIRT1 in the proliferation and osteoblastic differentiation of
      dental stem cells is unclear. The aim of this study was to assess the roles of
      SIRT1 in these processes using periodontal ligament stem cells (PDLSCs) and stem
      cells from apical papilla (SCAPs). A defined concentration of resveratrol, an
      SIRT1 activator, or nicotinamide, an SIRT1 inhibitor, was administered to PDLSCs,
      SCAPs, and a mixed group of the two cell lines, and their effects on these
      processes analyzed. Cell proliferation was tested using microtitration with a
      tetrazolium dye (MTT). Alkaline phosphatase (ALP) activity, mineralization
      ability, and the expression of osteoblastic differentiation-associated genes were
      assessed as well. These studies demonstrated that resveratrol could promote cell
      proliferation of all three groups in a gradually increasing trend over time. In
      contrast, nicotinamide suppressed the proliferation of the three cell lines. The
      results also showed that the markers of osteoblastic differentiation: ALP
      activity, mineralization ability, and the expression levels of the osteoblastic
      genes ALP, osteopontin, osteocalcin, and bone sialoprotein, were enhanced in the
      groups with resveratrol treatment. In contrast, following addition of
      nicotinamide, ALP activity, mineralization ability, and the expression levels of
      the osteoblastic genes were down-regulated in the cells. Together, these results
      suggest that the SIRT1 activator and inhibitor compounds, resveratrol and
      nicotinamide, function at high efficiency in adjusting cell proliferation, and
      that SIRT1 is a powerful regulator of osteoblastic differentiation of PDLSCs and
      SCAPs. In addition, co-culture of the two cell lines could promote their
      abilities of proliferation and osteogenic differentiation. 

PMID- 27050995
TI  - Insights into a hotspot in the Brasiliensis subcomplex (Hemiptera, Triatominae)
      by analysis of D2 domain of the nuclear gene 28S.
AB  - The Brasiliensis subcomplex is a monophyletic group formed by the species
      Triatoma brasiliensis brasiliensis, T. b. macromelasoma, T. juazeirensis, T.
      melanica, and T. sherlocki. However, using cytogenetic data and experimental
      hybrid crosses, T. lenti and T. petrochiae were also grouped into this
      subcomplex. This study aims to analyze the properties of hotspot in the D2 domain
      of the nuclear gene 28S in all species of the Brasiliensis subcomplex as well as
      T. lenti and T. petrochiae. These species show two transversions at position 385
      (G<->C and T<->G). We suggest that this mutation in haplotype 4 may be an initial
      molecular tool that supports the relationship of these species with the
      subcomplex. In addition to the transversion at haplotype 4, these species, aside
      from T. melanica, also possess a transversion at position 385 (G<->T) in
      haplotype 1. Thus, we describe the hotspot mutations of the D2 domain of the
      nuclear gene 28S for species in Brasiliensis subcomplex as follows: three
      transversions are present at position 385 of haplotypes 1 and 4, which are shared
      by members of the subcomplex as well as T. lenti and T. petrochiae. These
      transversions may be considered a synapomorphy between these species. However, we
      emphasize that new phylogenetic studies should be conducted to evaluate whether
      T. lenti and T. petrochiae are truly members of the Brasiliensis subcomplex. 

PMID- 27050996
TI  - Molecular cloning and gene expression analysis of cystatin C-like proteins in
      spinyhead croaker Collichthys lucidus.
AB  - Cystatins are natural tight-binding reversible inhibitors of cysteine proteases.
      In this study, a cDNA library was constructed from Collichthys lucidus using the
      SMART technique. A complete cDNA sequence with high identity to the conserved
      sequence of the cystatin C gene was cloned from the library using EST analysis
      and rapid amplification of cDNA ends (RACE), then subjected to further
      investigation. The full-length cDNA of cystatin C from C. lucidus (Clcys) was 699
      bp long, including a 5'-terminal untranslated region (5'-UTR) of 52 bp, a 3'-UTR
      of 290 bp, and an open-reading frame of 357 bp. The gene encoded a polypeptide of
      118 amino acids, constituting a predicted molecular weight of 12.875 kDa and a
      theoretical isoelectric point of 8.81. The amino acid sequence of Clcys possessed
      typical features of type II cystatins and had the highest identity with cystatin
      C of Pseudosciaena crocea (89%); therefore, it clustered with the cystatin C
      group in the UPGMA phylogenetic tree. Quantitative real-time reverse
      transcription analysis revealed that the highest expression was found in the
      kidney, followed by the liver, heart, and testis, with the lowest expression in
      muscle. Interestingly, Clcys had relatively low identity with cystatin C genes
      from other fish and mammals, and its expression pattern did not possess features
      of a housekeeping gene. Based on these findings, we suspect that the
      classification of cystatins in fish is somewhat confusing, and the identification
      of more cystatin gene sequences is needed before a definite conclusion can be
      drawn. 

PMID- 27050997
TI  - Glucocorticoid receptor expression in the tonsils of children with obstructive
      sleep apnea hypopnea syndrome.
AB  - The expression of glucocorticoid receptor-alpha and -beta (GR-alpha and GR-beta)
      in the tonsil tissues of children with and without obstructive sleep apnea
      hypopnea syndrome (OSAHS) was evaluated. A total of 30 children with OSAHS who
      underwent tonsillectomy in the Navy General Hospital from June 2012 to June 2014
      were enrolled as the experimental group, and 30 non-OSAHS children were enrolled
      as the control group. The diagnosis of OSAHS was confirmed by preoperative sleep
      monitoring. The expression of GR-alpha and GR-beta in tonsil tissues was detected
      using western blot and immunohistochemical analyses. GR-alpha and GR-beta were
      both expressed in the tonsil tissues of OSAHS and non-OSAHS patients. The
      expression of GR-alpha in the tonsil tissues of OSAHS children was significantly
      lower than that in the tonsil tissues of non-OSAHS children, while the expression
      of GR-beta in the tonsil tissues was similar between the two groups of children.
      Since it has been reported that GR-alpha expression is correlated to
      glucocorticoid therapy sensitivity, the sensitivity of children with OSAHS to
      glucocorticoid treatment may be lower than that in children who do not have
      OSAHS. However, the function of GR in children with OSAHS still requires further
      investigation. 

PMID- 27050998
TI  - miRQuest: integration of tools on a Web server for microRNA research.
AB  - This report describes the miRQuest - a novel middleware available in a Web server
      that allows the end user to do the miRNA research in a user-friendly way. It is
      known that there are many prediction tools for microRNA (miRNA) identification
      that use different programming languages and methods to realize this task. It is
      difficult to understand each tool and apply it to diverse datasets and organisms
      available for miRNA analysis. miRQuest can easily be used by biologists and
      researchers with limited experience with bioinformatics. We built it using the
      middleware architecture on a Web platform for miRNA research that performs two
      main functions: i) integration of different miRNA prediction tools for miRNA
      identification in a user-friendly environment; and ii) comparison of these
      prediction tools. In both cases, the user provides sequences (in FASTA format) as
      an input set for the analysis and comparisons. All the tools were selected on the
      basis of a survey of the literature on the available tools for miRNA prediction.
      As results, three different cases of use of the tools are also described, where
      one is the miRNA identification analysis in 30 different species. Finally,
      miRQuest seems to be a novel and useful tool; and it is freely available for both
      benchmarking and miRNA identification at
      http://mirquest.integrativebioinformatics.me/. 

PMID- 27050999
TI  - Development and characterization of Rift Valley fever virus-like particles.
AB  - Rift Valley fever (RVF) is an acute, febrile zoonotic disease that is caused by
      the RVF virus (RVFV) and spread by arthropod vectors. RVF is currently prevalent
      in Africa and the Arabian Peninsula, and causes substantial economic losses.
      Furthermore, this disease poses a serious threat to animal and human health in
      regions worldwide, making it a serious public health concern. However, RVFV
      vaccines for human use are still unavailable, and hence there is an urgent need
      for novel efficient vaccines against RVFV. Vaccine preparation techniques have
      become a crucial factor in developing new vaccines. In the current study, the N
      and G protein genes of RVFV were inserted into the pFastBacDual baculovirus
      expression vector downstream of the pP10 and pPH promoters. The resultant
      recombinant vector, pFastBacDual-S-M, was transfected into Sf9 insect cells by
      lipofection. The recombinant baculovirus, named rBac-N-G, was retrieved and
      infected into Sf9 insect cells to generate RVFV virus-like particles (VLPs).
      Using polyclonal antibodies against RVFV proteins in immunofluorescence and
      western blot analyses, we positively identified the presence of the RVFV proteins
      in VLP preparations. Sucrose density gradient centrifugation and transmission
      electron microscopy revealed that the morphology of the RVFV VLPs was consistent
      with previous reports of RVFV virions. This study describes a technique for
      efficient production of RVFV VLPs, and has laid the foundation for future VLP
      based RVFV vaccines. 

PMID- 27051000
TI  - De novo assembly and characterization of farmed blue fox (Alopex lagopus) global
      transcriptome using Illumina paired-end sequencing.
AB  - The blue fox (Alopex lagopus), a coat-color variant of the Arctic fox, is a
      domesticated fur-bearing mammal. In the present study, transcriptome data
      generated from a pool of nine different tissues were obtained with Illumina
      HiSeq2500 paired-end sequencing technology. After filtering from raw reads,
      32,358,290 clean reads were assembled into 161,269 transcripts and 97,252
      unigenes by the Trinity fragment assembly software. Of the assembled unigenes,
      37,967 were annotated in the National Center for Biotechnology Information (NCBI)
      Non-Redundant (NR) protein database and 26,264 in the Swiss-Prot database. Among
      the annotated unigenes, 24,839 and 24,267 were assigned using the Gene Ontology
      (GO) and euKaryotic Orthologous Groups (KOG) databases, respectively. Altogether,
      17,057 unigenes were mapped onto 227 pathways using the Kyoto Encyclopedia of
      Genes and Genomes database. In addition, 6394 simple sequence repeats were
      identified by examining 12,965 unigenes (>1 kb), which could contribute to the
      development of molecular markers. This study generated transcriptome data for the
      blue fox that will promote further progress in expression profiling studies, and
      provide a good annotation basis for genomic studies. 

PMID- 27051001
TI  - Positive evolution of the glycoprotein (GP) gene is related to transmission of
      the Ebola virus.
AB  - Ebola hemorrhagic fever is a fatal disease caused by the negative-strand RNA of
      the Ebola virus. A high-intensity outbreak of this fever was reported in West
      Africa last year; however, there is currently no definitive treatment strategy
      available for this disease. In this study, we analyzed the molecular evolutionary
      history and attempted to determine the positive selection sites in the Ebola
      genes using multiple-genomic sequences of the various Ebola virus subtypes, in
      order to gain greater clarity into the evolution of the virus and its various
      subtypes. Only the glycoprotein (GP) gene was positively selected among the 8
      Ebola genes, with the other genes remaining in the purification stage. The
      positive selection sites in the GP gene were identified by a random-site model;
      these sites were found to be located in the mucin-like region, which is
      associated with transmembrane protein binding. Additionally, different branches
      of the phylogenetic tree displayed different positive sites, which in turn was
      responsible for differences in the cell adhesion ability of the virus. In
      conclusion, the pattern of positive sites in the GP gene is associated with the
      epidemiology and prevalence of Ebola in different areas. 

PMID- 27051002
TI  - Correlation between the 677C>T polymorphism in the methylene tetrahydrofolate
      reductase gene and serum homocysteine levels in coronary heart disease.
AB  - The aim of the current study was to explore the correlation between serum
      homocysteine (HCY) levels and the methylene tetrahydrofolate reductase (MTHFR)
      gene 677C/T polymorphism and coronary heart disease (CHD). We consecutively
      enrolled 208 patients with CHD confirmed by CTA or coronary angiography from our
      hospital. An additional 200 healthy volunteers were enrolled as the control
      group. Serum HCY levels, MTHFR C677T genotype, and other related indicators were
      evaluated for the two groups. Compared to those in the control group, the serum
      HCY levels in the CHD patients were significantly higher (P < 0.05). The
      proportion of individuals with the heterozygous MTHFR CT genotype and homozygous
      mutant TT genotype among CHD patients was significantly higher than that in the
      control group (P < 0.05). In the acute coronary syndrome (ACS) subgroup, the
      proportion of those with the CT and TT genotypes was significantly higher than
      that of the stable CHD subgroup (P < 0.05). In summary, serum HCY levels were
      elevated in CHD patients, and the frequency of the CT and TT genotypes were also
      significantly increased, especially among the ACS subgroup. Taken together, this
      suggests that serum HCY levels and MTHFR C677T genotypes are correlated with CHD.

PMID- 27051003
TI  - Pivotal role of microRNA-9 in osteosarcoma tumorigenesis and tumor progression.
AB  - MicroRNA-9 (miR-9) has a well-established role in various tumors; the clinical
      significance and potential mechanism of miR-9 in human osteosarcoma (OS) has not
      been elucidated. The aim of this study was to investigate the mechanism and role
      of miR-9 expression in osteosarcoma cells. miR-9 expression in the OS cell line
      MG-63 and OS tissues was compared to that in a human osteoblastic cell line (hFOB
      1.19) and adjacent normal tissues, respectively, by reverse transcriptase
      polymerase chain reaction. miR-9 expression was downregulated by introducing
      small interfering RNA against miR-9 (si-miR-9) into the cells, and the
      proliferative, migratory, and invasive capacities of si-miR-9-transfected MG-63
      cells were compared to those of control MG-63 cells. miR-9 was significantly
      upregulated in OS tissues and cell lines compared to the corresponding non
      cancerous bone tissues (P < 0.05) and human osteoblastic cell line (P < 0.05),
      respectively. Upregulated miR-9 expression was also associated with increased
      cell proliferation (P < 0.05), migration (P < 0.05), and invasion (P < 0.05), and
      decreased apoptotic ability (P < 0.05). These results suggest that miR-9 may play
      a pivotal role in tumorigenesis and tumor progression in osteosarcoma. 

PMID- 27051004
TI  - A new method for estimating the number of non-differentially expressed genes.
AB  - Control of the false discovery rate is a statistical method that is widely used
      when identifying differentially expressed genes in high-throughput sequencing
      assays. It is often calculated using an adaptive linear step-up procedure in
      which the number of non-differentially expressed genes should be estimated
      accurately. In this paper, we discuss the estimation of this parameter and point
      out defects in the original estimation method. We also propose a new estimation
      method and provide the error estimation. We compared the estimation results from
      the two methods in a simulation study that produced a mean, standard deviation,
      range, and root mean square error. The results revealed that there was little
      difference in the mean between the two methods, but the standard deviation,
      range, and root mean square error obtained using the new method were much smaller
      than those produced by the original method, which indicates that the new method
      is more accurate and robust. Furthermore, we used real microarray data to verify
      the conclusion. Finally we provide a suggestion when analyzing differentially
      expressed genes using statistical methods. 

PMID- 27051005
TI  - Nucleolar-persistence phenomenon during spermatogenesis in genus Meccus
      (Hemiptera, Triatominae).
AB  - The Triatominae subfamily consists of 150 species in 18 genera, grouped into six
      tribes. In cytogenetics, triatomines are important biological models because they
      have holocentric chromosomes and nucleolar persistence in meiosis. The phenomenon
      of nucleolar persistence has been described for 23 species of triatomine in three
      genera: Triatoma, Rhodnius, and Panstrongylus. However, new species and genera
      should be analyzed to assess whether nucleolar persistence is a peculiarity of
      Triatominae. Thus, this study aimed to analyze nucleolar behavior during
      spermatogenesis of Meccus pallidipennis and M. longipennis, focusing on the
      nucleolar-persistence phenomenon. Through the analysis of spermatogenesis, more
      specifically of meiotic metaphase, we observed the phenomenon of nucleolar
      persistence in M. pallidipennis and M. longipennis, represented by remnants of
      nucleolar material in metaphase. Thus, although nucleologenesis of new species,
      and, especially, new genera, should be analyzed, this study confirms for the
      first time the phenomenon of nucleolar persistence in the genus Meccus.
      Therefore, we emphasize the importance of new studies in this area in order to
      assess whether this phenomenon is truly a synapomorphy of these hematophagous
      insects. 

PMID- 27051006
TI  - Chemical signatures in the developmental stages of Protopolybia exigua.
AB  - The chemical signature of social insects is very important for communication, and
      specific signs of each colony and its individuals are acquired throughout their
      development. This chemical signature can also be related to the composition of
      the materials employed during nest construction. Furthermore, the venom also
      contains important chemicals required for the maintenance of wasp colonies.
      Therefore, the objective of this study was to evaluate the chemical composition
      of the wasp Protopolybia exigua along its different development stages, including
      the nest substrate and the venom of adult worker at different ages. To achieve
      this, gas chromatography coupled to mass spectrometry was used. The results show
      that the chemical cuticular compounds present in different stages of development,
      and in the nest of P. exigua, are qualitatively similar, but quantitatively
      different, demonstrating that these compounds can be used as signals for the
      identification of co-specific individuals within the colonies. However, there was
      no significant variation in these compounds between different colonies, which may
      be related to the parental level between the colonies and due to them sharing the
      same resources. The non-polar compounds of the venom vary significantly according
      to the age of the workers, probably due to their different roles within the
      colony, and there was a clear increase in the complexity of the compounds as the
      wasps aged. Older wasps perform higher-risk activities, such as foraging, and
      therefore need to make more use of venom. 

PMID- 27051007
TI  - Evaluation of the efficiency of artificial neural networks for genetic value
      prediction.
AB  - Artificial neural networks have shown great potential when applied to breeding
      programs. In this study, we propose the use of artificial neural networks as a
      viable alternative to conventional prediction methods. We conduct a thorough
      evaluation of the efficiency of these networks with respect to the prediction of
      breeding values. Therefore, we considered eight simulated scenarios, and for the
      purpose of genetic value prediction, seven statistical parameters in addition to
      the phenotypic mean in a network designed as a multilayer perceptron. After an
      evaluation of different network configurations, the results demonstrated the
      superiority of neural networks compared to estimation procedures based on linear
      models, and indicated high predictive accuracy and network efficiency. 

PMID- 27051008
TI  - MicroRNA analysis in model species based on evolutionary rates.
AB  - MicroRNAs (miRNAs) are major post-transcriptional regulators of gene expression.
      In an attempt to gain insights into miRNAs at the macroevolutionary level, we
      performed a systematic analysis of miRNAs in six model organisms based on their
      evolutionary rates. First, we calculated their miRNA evolutionary rates, and
      found that they did not correlate with the complexity of the organisms. A
      correlation between evolutionary rates and single nucleotide polymorphisms (SNPs)
      in the miRNA sequence suggested that slow-evolving miRNAs in humans tolerate more
      SNPs than miRNAs with similar evolutionary rates in other species. However, fast
      evolving miRNAs had lower SNP densities in humans than in the fruit fly. We also
      found that evolutionary rates were correlated with the proportion of parasite or
      clustered miRNAs. This correlation exhibited a different pattern in zebrafish,
      which may be related to significant genome duplication in the early vertebrates.
      The minimized free energy of the miRNA stem-loop structure was not correlated
      with the evolutionary rates of any species in our analysis. After evaluating
      relative miRNA expression levels, we observed that newly emerged miRNAs in
      complex species would integrate into the gene network at a faster pace and be
      functionally important; therefore, miRNAs may have accelerated human evolution. 

PMID- 27051009
TI  - STAT1 inhibitor alleviates spinal cord injury by decreasing apoptosis.
AB  - Spinal cord injury (SCI) is typically caused by trauma or disease, and it
      severely affects patients' motor function. The relationship between signal
      transducers and activators of transcription-1 (STAT1) and neuronal death after
      cerebral focal ischemia has been comprehensively studied, but its role in SCI
      remains largely unknown. This study investigated the protective effect of an
      STAT1 inhibitor on SCI. Thirty SD rats were SCI-induced and were then randomly
      divided into two groups (N = 15 each), either receiving STAT1 or the STAT1
      inhibitor S1491 by intraperitoneal injection. The motor dysfunction of the rats
      was evaluated by behavioral scores, followed by the examination of SCI by
      hematoxylin and eosin staining. Apoptosis was also detected by Western blot and
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)
      assay. The motor functions of rats receiving STAT1 did not score as well as the
      STAT1 inhibitor group (P < 0.01). Further assays showed remarkable improvements
      in pathological damage to spinal code tissue in STAT1 inhibitor-treated rats,
      along with lower Bax and higher Bcl-2 expression. The STAT1 inhibitor also
      suppressed the occurrence of TUNEL-positive cells compared to the STAT1-treated
      group. In summary, we suggest that the STAT1 inhibitor alleviates SCI by
      decreasing apoptosis. 

PMID- 27051010
TI  - Genetic background of Escherichia coli isolates from peritoneal dialysis patients
      with peritonitis and uninfected control subjects.
AB  - Escherichia coli is the most common cause of Gram-negative peritonitis resulting
      in peritoneal function deterioration as well as poor clinical outcome in
      continuous ambulatory peritoneal dialysis (PD) patients. In this study, we
      analyzed the phylogenetic background and genetic profile of the E. coli isolates
      and sought to determine the characteristics of specific bacteria associated with
      peritonitis. E. coli isolates from 56 episodes of peritonitis in 46 PD patient
      cases and rectal isolates from 57 matched PD control patient cases were compared
      for both phylogenetic groups and the presence of virulence factors (VFs). There
      were no significant differences in terms of demographic data between the
      peritonitis and control groups. Peritonitis isolates exhibited a significantly
      greater prevalence of 8 VFs. In multivariate logistic regression analysis, kpsMT
      II (group 2 capsule synthesis) was the strongest VF predictor of peritonitis (OR
      = 8.02; 95%CI = 3.18-20.25; P < 0.001), followed by traT (serum-resistance
      associated outer membrane protein) (OR = 3.83; 95%CI = 1.33-11.03; P = 0.013).
      The pathogenic groups of E. coli contained a higher concentration of individual
      VFs compared to the commensal groups. The prevalence of pathogenic E. coli was
      much higher in peritoneal isolates than rectal isolates (64.3 vs 31.6%, P =
      0.001). Our results indicate that the E. coli peritonitis and rectal isolates are
      different in PD patients. The specific VFs associated with peritonitis isolates
      may directly contribute to the pathogenesis of peritonitis. 

PMID- 27051011
TI  - Development and characterization of novel microsatellite markers for Ginkgo
      biloba using 454 pyrosequencing.
AB  - As a "living fossil" that is used to understand the evolutionary history of seed
      plants, Ginkgo biloba is a well-known multipurpose tree with edible seeds,
      medicinal properties, and ornamental value, but little is known about its genetic
      diversity. Microsatellite, or simple sequence repeat (SSR), markers have proven
      to be powerful tools for genetic studies of plants. In this study, we isolated 30
      novel polymorphic microsatellite loci in G. biloba using 454 pyrosequencing. The
      characteristics of these loci were tested with 48 cultivars. The number of
      alleles (NA) per locus ranged from two to seven. The observed (HO) and expected
      (HE) heterozygosities ranged from 0.000 to 0.750 and from 0.021 to 0.792, with an
      average of 0.326 and 0.443, respectively. In terms of genetic diversity in the
      Ginkgo population, NA was 3.300, NE was 2.090, I was 0.782, HO was 0.326, and HE
      was 0.443. These polymorphic SSRs will be useful for the assessment of population
      genetic diversity and resource conservation of G. biloba. 

PMID- 27051012
TI  - Genetic analysis of water-deficit response traits in maize.
AB  - A set of sixty inbred lines of maize (Zea mays L.) were screened in the
      greenhouse at the seedling stage under both normal and water-deficit conditions.
      Six water deficit-tolerant inbred lines were selected based on root to shoot
      ratios. These selected lines were crossed in a diallel pattern. The parental, F1,
      and reciprocal cross plants were planted in a field under both normal and water
      deficit conditions. Normal irrigation was applied to the control set, while the
      water-deficit set received 50% of normal irrigation levels. Analyses of variance
      of various morpho-physiological parameters identified significant differences
      among the selected lines under both conditions, indicating the presence of
      significant genetic variability. Variance components for general combining
      ability (GCA), specific combining ability (SCA), and reciprocal effects for all
      the parameters were estimated to determine the relative importance of additive
      and non-additive or dominance type of gene action. Variance components for GCA
      were larger than for SCA indicating the preponderance of additive types of gene
      action for all the traits under study. Hybrids developed from inbred lines W-10
      and W-64SP proved to have the best grain yield under normal and water-deficit
      conditions. Under water-deficit conditions, the best performing cross was B-34 x
      W-10. Hence, these inbred lines and the hybrids might be of value in future
      breeding programs. 

PMID- 27051013
TI  - Association between the MTHFR C677T gene polymorphism and essential hypertension
      in South West Cameroon.
AB  - The association of the methylenetetrahydrofolate reductase (MTHFR) C677T gene
      polymorphism and essential hypertension has been reported but with controversial
      results in diverse populations in Asia and Europe, thereby suggesting a
      dependency on ethnicity. The aim of this study was to investigate the association
      between the MTHFR C677T polymorphism and essential hypertension in a Cameroonian
      population (Bantu ethnic group) of the South West Region. Analysis of
      anthropometric and biochemical data in hypertensive and normotensive subjects
      revealed that age, systolic blood pressure, diastolic blood pressure, low-density
      lipoprotein cholesterol, serum total cholesterol, and triglycerides are
      independent risk factors for essential hypertension. Substitution of thymine for
      cytosine at position 667 of the MTHFR gene was determined by polymerase chain
      reaction-restriction fragment length polymorphism. Genotype frequencies were
      found to be 7.3% CC, 58.5% CT, and 34.1% TT for hypertensive subjects compared to
      90.0% CC, 10.0% CT, and 0.0% TT for normotensives. Allele frequencies were
      obtained as 36.6% C and 63.4% T for hypertensive subjects and 95.0% C and 5.0% T
      for normotensive subjects. These results reveal that the T allele predisposes
      individuals to hypertension. Therefore, there is an association between variants
      of the MTHFR gene and hypertension in Cameroonian patients from the South West
      region. 

PMID- 27051014
TI  - Increased expression of the lncRNA BANCR and its prognostic significance in human
      osteosarcoma.
AB  - Long noncoding RNAs (lncRNAs) play important roles in the formation and
      progression of many types of human malignancies. The aim of our study was to
      investigate the expression and biological functions of the lncRNA BRAF-activated
      noncoding RNA (BANCR) in human osteosarcoma. BANCR expression was quantified by
      real-time PCR in human osteosarcoma cell lines and tissues. We analyzed the
      association between BANCR levels and clinicopathological factors and patient
      prognosis. MTT, flow cytometric, and transwell invasion assays were performed to
      observe the effects of BANCR on MG-63 cell biological behaviors. BANCR
      overexpression was observed in osteosarcoma cell lines and clinical specimens.
      Increased BANCR expression was significantly associated with large tumor size,
      positive distant metastasis, and advanced clinical stage. High BANCR expression
      in osteosarcoma was an independent predictor of poor survival. Downregulation of
      BANCR inhibited MG-63 cell proliferation and invasion and promoted cell apoptosis
      in vitro. These findings suggested that BANCR may act as a tumor promoter in
      osteosarcoma and could serve as a potential therapeutic target for this disease.

PMID- 27051015
TI  - Analysis of DRB3 gene polymorphisms in Jafarabadi, Mediterranean, and Murrah
      buffaloes from Brazil.
AB  - The DRB3 gene is an MHC class II gene that has a high degree of polymorphism with
      more than 100 alleles described in cattle. This variation contributes to
      differences among individuals in immune responsiveness and disease resistance. In
      this study, we searched for allelic variants in exon 2 of the DRB3 gene in 80
      river buffaloes of three breeds in Brazil using a PCR-RFLP technique. The PCR
      product showed genetic polymorphism when digested with RsaI, PstI or HaeIII
      restriction enzymes. In total, 16 restriction patterns were identified: nine
      restriction patterns and 16 genotypes were found with RsaI; four restriction
      patterns and nine genotypes were found with HaeIII; and, three restriction
      patterns and four genotypes were found with PstI. Three RFLP patterns were
      exclusive to Jafarabadi buffaloes (RsaI-b, RsaI-c and RsaI-f) and three others
      were only observed in Mediterranean buffaloes (RsaI-g, RsaI-h and PstI-y).
      Jafarabadi buffaloes had a larger number of RFLP patterns than Mediterranean and
      Murrah breeds. The analysis showed that the DRB3 exon 2 was highly polymorphic,
      with the highest degree of polymorphism in Mediterranean buffaloes. This study
      provides the first assessment of allelic variation among three different buffalo
      breeds from Brazil and provides a basis for further investigations into the
      association between the DRB3 alleles and disease resistance. 

PMID- 27051016
TI  - Effect of procyanidine on VEGFR-2 expression and transduction pathway in rat
      endothelial progenitor cells under high glucose conditions.
AB  - The protective effect of procyanidine and its oligomers against high glucose
      mediated oxidative stress injury in endothelial progenitor cells (EPCs), and
      effect of procyanidin on vascular endothelial growth factor receptor-2 (VEGFR-2)
      expression and downstream signal pathway were analyzed in vitro. Rat bone marrow
      mononuclear cells were isolated, cultured under normal and high glucose (HG)
      conditions, and the changes in cell morphology observed. The EPCs were
      identified, and the oxidative stress products produced by EPCs (under normal and
      HG conditions) were quantified. Subsequently, an appropriate number of EPCs were
      cultured with and without procyanidin (OPC), and the MDA concentration and
      relative expression of VEGFR-2, AKT, IkappaB-alpha, and nuclear factor (NF)
      kappaB were detected 1, 3, 5, and 7 days post-culture. We observed minor (round,
      translucent, gradually adhering) and significant (fusiform morphology/pebble
      distribution) cell morphological changes 3 and 7 days post-culture, respectively.
      Apoptosis and oxidative stress product release in EPCs cultured with HG increased
      significantly compared to the control group (P < 0.05). The oxidative stress
      product generation and relative expression of VEGFR-2, AKT, IkB-alpha, and NF
      kappaB were not significantly affected by OPC addition in normal glucose
      conditions (P > 0.05); alternately, products generated as a result of oxidative
      stress were significantly reduced, the relative expression of VEGFR-2, AKT, and
      NF-kappaB protein was upregulated, and that of IkappaB-alpha was downregulated (P
      < 0.05) in HG + OPC EPCs. Therefore, procyanidin may promote cell proliferation
      by alleviating oxidative damage to EPCs under HG conditions, and upregulating
      VEGFR-2 expression and its downstream signal pathway. 

PMID- 27051017
TI  - Association between a point mutation at the -743-bp region of the transthyretin
      (TTR) gene and familial vitreous amyloidosis.
AB  - The aim of this study was to identify changes in the base sequence of the
      upstream regulatory region of the transthyretin (TTR) gene. Whole-blood DNA was
      extracted from ten subjects belonging to a family with familial amyloidosis
      vitreoretinopathy; the upstream regulatory sequence was amplified by polymerase
      chain reaction, detected by gel electrophoresis, and sequenced. The DNA sequence
      of the upstream regulatory region of the TTR gene was successfully sequenced, and
      a point mutation (-743A->T) was identified in six of the ten blood samples: four
      patients and two family members without disease incidence. Therefore, a point
      mutation was identified in the upstream regulatory region of the TTR gene in a
      Han Chinese family with familial vitreous amyloidosis. 

PMID- 27051018
TI  - Cytogenetic analysis of Triatoma pseudomaculata Correa and Espinola, 1964
      (Hemiptera, Triatominae) from different Brazilian states.
AB  - Triatoma maculata and T. pseudomaculata are allopatric; however, it is believed
      that T. maculata was introduced into the Brazilian northeast by passive
      transportation of the nymphs between the feathers of migratory birds, followed by
      the speciation of T. pseudomaculata. T. pseudomaculata is the second most
      epidemiologically important species in the northeast of Brazil after T.
      brasiliensis. Therefore, given the broad range of T. pseudomaculata, the
      objective of the present study was to cytogenetically analyze different
      populations of T. pseudomaculata from different Brazilian states in order to
      investigate possible intraspecific chromosomal variation between them. Three
      adult T. pseudomaculata males from each population (Pernambuco, Ceara, Paraiba,
      Bahia, Rio Grande do Norte, and Piaui) were analyzed by lacto-acetic orcein and C
      banding. All of the specimens analyzed exhibited the same cytogenetic
      characteristics, i.e., 22 chromosomes (20 autosomes and XY), a chromocenter
      formed by the X and Y sex chromosomes and one pair of autosomes, and
      heterochromatin blocks in three or four pairs of autosomes. These data confirm
      that all of the populations analyzed were T. pseudomaculata, and although they
      may be subject to different selection pressures they have maintained the genetic
      integrity that characterizes the species. 

PMID- 27051019
TI  - BMP6 and BMP4 expression in patients with cancer-related anemia and its
      relationship with hepcidin and s-HJV.
AB  - In the present study, we investigated BMP6 and BMP4 expression in patients with
      cancer-related anemia (CRA) as well as its relationship with hepcidin and s-HJV.
      The avidin-biotin system enzyme-linked immunosorbent assay was used to test serum
      levels of BMP6, BMP4, s-HJV, and hepcidin in 53 cancer patients with anemia and
      52 control cancer patients without anemia. Serum levels of BMP6 and hepcidin in
      the anemia group were 434.53 +/- 212.11 ng/mL and 5.68 +/- 3.89 MUg/L,
      respectively. In the non-anemia cancer group, serum BMP6 and hepcidin levels were
      334.37 +/- 171.32 ng/mL and 4.60 +/- 2.28 MUg/L, which were significantly lower
      than the levels for the CRA group (P < 0.05). In addition, the serum level of s
      HJV was 0.69 +/- 0.28 ng/mL in the CRA group, which was significantly lower
      compared to that for the non-anemia group (1.07 +/- 1.00 ng/mL, P < 0.01). There
      were no significant differences in BMP4 expression between the two groups. BMP6
      was negatively correlated with s-HJV and Hb (r = -0.2536 and -0.2949, P < 0.01),
      but was not correlated with hepcidin. Similarly, BMP4 expression was not
      correlated with Hb, s-HJV, or hepcidin. Our study shows that patients with CRA
      had high expression of BMP6 and hepcidin and low expression of s-HJV. BMP6 was
      found to be negatively correlated with s-HJV; both regulate hepcidin expression
      and play important roles in the development of anemia. 

PMID- 27051020
TI  - Prevalence of human papillomavirus genotypes among women with cervical lesions in
      the Shaanxi Province of China.
AB  - This study aimed to investigate human papilloma virus (HPV) genotypes among women
      with cervical lesions in Shaanxi Province, China, to obtain information regarding
      cervical lesion prevention and treatment. The study included 4508 HPV-positive
      subjects; cervical swab specimens were collected and tested for HPV infection
      status and HPV genotypes using polymerase chain reaction and reverse dot-blot
      hybridization. Women positive for HPV with cervical lesions, including chronic
      cervicitis, cervical intraepithelial neoplasia, and cervical squamous cell
      carcinoma (SCC), were examined; HPV-positive women with no cervical lesions were
      controls. Data were pooled and weighted estimates have been presented. For women
      with no cervical lesions and positive for one HPV genotype, HPV 52, 16, 58, 81,
      33, and 56 were the most common; for multiple-HPV genotype infection, HPV 16, 52,
      6, 18, 58, and 66 were the most common. Collectively, HPV 16, 58, 52, 18, 33, and
      81 were the most common in women with cervical lesions. HPV 16 comprised 26.71%
      of single-genotype and 15.64% of multiple-genotype infections. The proportion of
      HPV-16-positive cases was 29.15%, which was the highest among all HPV genotypes
      (P < 0.01). Single-HPV genotype infection was the most common in cervical HPV
      infection (77.48%); infection with two HPV genotypes comprised 72.22% of multiple
      genotype infections. The proportion of single-low-risk HPV genotype infections
      decreased with increase in cervical lesion severity; there were no single- or
      multiple-low-risk genotype HPV infections in cervical SCC patients. The
      proportion of multiple-genotype HPV infections with at least one high-risk
      genotype increased with cervical lesion severity. 

PMID- 27051021
TI  - Molecular phylogeny of Lathyrus species: insights from sequence-related amplified
      polymorphism markers.
AB  - Sequence-related amplified polymorphism (SRAP) markers were used to evaluate the
      intra- and interspecific variation among 40 Lathyrus genotypes (four species)
      (Fabaceae). Ten SRAP primer combinations resulted in a total of 94 bands, and
      they exhibited high interspecific variability. The genetic differentiation among
      Lathyrus, estimated using AMOVA, was highly significant. The results indicated
      that 58% of the total genetic variation existed among species, and 42% of the
      differentiation was within species. This was explained by the high level of
      genome conservation of these species as well as the recent and slow evolution of
      this genus. These results were confirmed by the topology of the neighbor-joining
      cladogram and the results of the principal coordinate analysis. Our data support
      previous results based on seed protein diversity. These results make SRAP markers
      choice markers for the study of functional polymorphism that is directly related
      to the transcriptomic data. The SRAP markers used in this study provide an
      accurate picture of the population structure within Lathyrus germplasm, which is
      critically important information for the design of genetic diversity and
      structure analyses. Moreover, further extensive studies are necessary to fully
      examine other Lathyrus species and tests that adopt the SRAP technique to enrich
      the Lathyrus library for next-generation sequencing, thus providing a potent
      protocol for the study of polymorphism. 

PMID- 27051022
TI  - Expression of TRPM8 in diabetic rats and its relationship with visceral pain
      stimulation.
AB  - Transient receptor potential cation channel, subfamily M, member 8 (TRPM8) is a
      nonselective cation channel and a candidate for cold sensation signaling, but the
      relationship between TRPM8 and diabetes remains unclear. In the present study, we
      determined the expression levels of TRPM8 messenger RNA (mRNA) and the levels of
      the TRPM8 protein in the bladder tissue of diabetic rats. We also investigated
      the correlation between TRPM8 expression and the visceral pain stimulation
      related factor, calcitonin gene-related peptide (CGRP) in diabetic rats. The rats
      were sacrificed 3, 5, 7, and 15 days after streptozotocin injection, and blood
      was collected from their tail veins to determine the blood glucose levels.
      Bladder tissue was removed to assess the expression of TRPM8 mRNA by reverse
      transcription-polymerase chain reaction, and the expression of the TRPM8 protein
      by western blotting. After administering electrical stimulation (5 V/1 Hz), the
      expression levels of TRPM8 and CGRP proteins were determined. Our results
      revealed that the blood glucose level, and TRPM8 mRNA and TRPM8 protein
      expression levels increased significantly in the diabetic rats. Spinal tissue
      protein expression levels of both TRPM8 and CGRP also increased significantly
      following electrical stimulation. This possibly indicates that TRPM8 is closely
      associated with visceral pain stimulation, and could be an independent prognostic
      biomarker for diabetes. 

PMID- 27051023
TI  - Association of MMP3 genotype with susceptibility to frozen shoulder: a case
      control study in a Chinese Han population.
AB  - Genetic factors may play an important role in frozen shoulder etiology, which may
      involve matrix metalloproteinase-3 (MMP3) gene polymorphisms. In this study, we
      examined single nucleotide polymorphisms in MMP3 for their association with
      frozen shoulder susceptibility in a Chinese Han population. The rs591058,
      rs650108, and rs679620 polymorphisms in the MMP3 gene were genotyped in 112
      subjects diagnosed as having frozen shoulder and in 143 healthy controls.
      rs650108 was found to be significantly associated with an increased risk of
      frozen shoulder. For other single nucleotide polymorphisms, no statistically
      significant associations with frozen shoulder were found. In conclusion, our data
      demonstrated that the MMP3 rs650108 variant was significantly associated with
      increased frozen shoulder susceptibility in a Chinese Han population. 

PMID- 27051024
TI  - Role of ERCC2 and ERCC3 gene polymorphisms in the development of osteosarcoma.
AB  - We conducted a case-control study to investigate the role of common SNPs in ERCC2
      (rs13181 and rs1799793) and ERCC3 (rs4150441 and rs4150506) in the development of
      osteosarcoma. A 1:2 matched case-control study was conducted. Between January
      2012 and December 2013, 141 patients with pathologically diagnosed osteosarcoma
      and 282 controls were recruited in our study. Genotyping of ERCC2 rs13181 and
      rs1799793 as well as ERCC3 rs4150441 and rs4150506 were performed using
      polymerase chain reaction coupled with restriction fragment length polymorphism.
      The genotype distributions of ERCC2 rs13181 and rs1799793 as well as ERCC3
      rs4150441 and rs4150506 showed no significant difference between patients with
      osteosarcoma and controls, as analyzed by c2 tests. Multivariate logistic
      regression analysis did not reveal significant associations between ERCC2
      rs13181/rs1799793 or ERCC3 rs4150441/ rs4150506 gene polymorphisms and the
      development of osteosarcoma in codominant, dominant, and recessive models. In
      conclusion, we did not find any association between ERCC2 or ERCC3 gene
      polymorphisms and the development of osteosarcoma. Future studies with larger
      sample sizes may contribute in elucidating the impact of ERCC2 and ERCC3 gene
      polymorphisms on osteosarcoma risks. 

PMID- 27051025
TI  - Association between the PADI4 -94G/A polymorphism and rheumatoid arthritis: a
      meta-analysis in the Chinese population.
AB  - Although a number of studies have been conducted on the association between the
      peptidylarginine deiminase (PADI4) -94G/A polymorphism and rheumatoid arthritis
      (RA) in the Chinese population, the association remains elusive and
      controversial. To clarify the impact of the PADI4 -94G/A polymorphism on the risk
      of RA, a meta-analysis was performed in the Chinese population. Related studies
      were identified from databases such as, Springer Link, Ovid, Chinese Wanfang Data
      Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and
      Chinese Biology Medicine (CBM) up to May 21, 2015. Pooled odds ratios (ORs) and
      95% confidence intervals (CIs) were used to assess the strength of associations.
      A total of 10 studies with 2783 RA cases and 2887 controls were included in this
      meta-analysis. Overall, a significantly elevated risk of RA was associated with
      all variants of PADI4 -94G/A (A vs G: OR = 1.24, 95%CI = 1.15-1.34; AA + GA vs
      GG: OR = 1.45, 95%CI = 1.29-1.62; AA vs GG: OR = 1.49, 95%CI = 1.28-1.73; AA vs
      GG + GA: OR = 1.19, 95%CI = 1.04-1.35). Subgroup analyses stratified by
      geographic areas and source of controls revealed significant results in the
      population-based studies in North and South China. In conclusion, this meta
      analysis showed that the PADI4 -94G/A variants may influence RA risk in the
      Chinese population. However, further studies with gene-gene and gene-environment
      interactions are required for definite conclusions. 

PMID- 27051026
TI  - Molecular characterization of carbapenemase genes in Acinetobacter baumannii in
      China.
AB  - Acinetobacter baumannii is an aerobic non-motile Gram-negative coccobacillus, and
      it is one of the most important nosocomial pathogens worldwide. The aim of this
      study was to determine the molecular epidemiology of the outbreak strains.
      Between March 2011 and March 2014, a total of 205 strains of A. baumannii were
      isolated from patients at the Nanyang City Center Hospital. The blaOXA-23, blaOXA
      24, blaOXA-51, and blaOXA-58 genes were amplified by multiplex polymerase chain
      reaction. We found that 68 (33.17%) strains were positive for the blaOXA-23 gene,
      and 88.24% of these 68 showed resistance to carbapenems, while 11.76% were
      sensitive to carbapenems. The blaOXA-51 gene was found in 132 (64.39%) strains,
      and 17.42% of these were resistant to carbapenems while 82.58% were sensitive to
      carbapenems. Moreover, 5 (2.44%) strains were positive for blaOXA-58, of which
      80% were resistant to carbapenems and 20% were sensitive to carbapenems. We found
      that A. baumannii showed 100% drug resistance to ampicillin, cefotetan,
      cefazolin, and cefoperazone. Our findings suggest that the blaOXA-23 and blaOXA
      51 genes are most frequently identified in A. baumannii, while blaOXA-23 is the
      most important gene for resistance to carbapenems. 

PMID- 27051027
TI  - Matrix metalloproteinase 9 -1562C/T polymorphism increased protein levels in
      patients with colorectal cancer in a sample from southeastern Brazil.
AB  - We examined whether the allelic and/or genotypic profile of locus -1562C/T of the
      matrix metalloproteinase (MMP-9) gene influences the protein expression levels of
      MMP-9 in patients with colorectal cancer (CRC) compared with controls. A total of
      104 patients with CRC and 84 controls were evaluated. Peripheral blood was
      collected from both groups and DNA extraction was performed for -1562C/T
      genotyping; the plasma was used for MMP-9 quantification. The CT genotype was
      associated with increased MMP-9 expression (P = 0.0211). High levels of protein,
      independently of polymorphisms, were observed in the patient group (P < 0.0001)
      compared to controls. Mucinous tumors with signet ring cells were more frequent
      in females (P = 0.0177). Overall, patients older than 50 years showed a
      significant risk of developing CRC (P = 0.0001). MMP-9 plasma expression was
      increased in patients with CRC compared to controls, particularly in those with
      the heterozygous -1562CT genotype. 

PMID- 27051028
TI  - Association between ERCC5 gene polymorphisms and gastric cancer risk in a Chinese
      population.
AB  - We conducted a hospital-based case-control study to investigate the association
      between 3 common SNPs in the ERCC5 gene (rs1047768, rs751402, and rs17655) and
      the risk of developing gastric cancer. Between January 2013 and December 2014,
      samples were collected from 216 gastric cancer patients and 216 control subjects.
      ERCC5 rs1047768, rs751402, and rs17655 polymorphisms were genotyped by polymerase
      chain reaction combined with restriction fragment length polymorphism analysis.
      By conditional logistic regression analysis, the GG genotype of rs17655 was found
      to be associated with an elevated risk of gastric cancer in a codominant model,
      and the adjusted OR (95%CI) was 1.96 (1.10-3.50). Moreover, in a dominant model,
      the CG + GG genotype of rs17655 was correlated with an increased risk of gastric
      cancer compared to the CC genotype (OR = 1.48; 95%CI = 1.00-2.22). rs1047768 and
      rs751402 were not significantly correlated with an increased or decreased gastric
      cancer risk. 

PMID- 27051029
TI  - Association of the interleukin-10 gene -1082A/G genetic polymorphism with risk of
      ischemic stroke in a Chinese population.
AB  - We investigated the possible association between two single nucleotide
      polymorphisms of IL10 (-1082A/G and -592C/A) and susceptibility to ischemic
      stroke. In total, 335 patients with proven ischemic stroke and 335 control
      subjects were recruited from Xinxiang Central Hospital between March 2013 and May
      2015. The IL10 -1082A/G and -529C/A polymorphisms were investigated by polymerase
      chain reaction-restriction fragment length polymorphism. When compared with the
      control subjects, patients with ischemic stroke were more likely to be male, have
      a habit of tobacco smoking, have higher BMI, have hypertension or diabetes
      mellitus, and have higher levels of TC, LDL-C, HDL-C, and TG. The multivariate
      logistic regression analyses revealed that the AA genotype of IL10 -1082A/G was
      significantly associated with development of ischemic stroke in a Chinese
      population compared with the GG genotype (OR = 1.93, 95%CI = 1.15-3.25). In the
      dominant model, the association between GA+AA genotype of IL10 -1082A/G and risk
      of ischemic stroke was also significant compared with the GG genotype, and the
      adjusted OR (95%CI) for the GA+AA genotype was 1.41 (1.02-1.94). Thus, our study
      suggests that IL10 gene polymorphisms contribute to the development of ischemic
      stroke. 

PMID- 27051030
TI  - Association of LRP5 Ala1330Val polymorphism with fracture risk: a meta-analysis.
AB  - Numerous studies have evaluated the association between the Ala1330Val
      polymorphism of the low-density lipoprotein receptor-related proteins 5 (LRP5)
      gene and fracture risk. However, the specific association is still controversial.
      The aim of this study was to investigate their correlation via meta-analysis. and
      EMBASE databases were searched, and data were extracted independently by two
      reviewers. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs)
      were used to assess the strength of the associations. Statistical analysis was
      performed using the STATA 12.0 software. Seven studies, involving 808 cases and
      1586 controls, were included in the analysis. Meta-analysis results showed no
      significant association between the LRP5 Ala1330Val polymorphism and fracture
      risk (ValVal vs AlaAla: OR = 1.25, 95%CI = 0.82-1.91; AlaVal vs AlaAla: OR =
      1.16, 95%CI = 0.95-1.42; dominant model: OR = 1.77, 95%CI = 0.96-1.41; recessive
      model: OR = 1.21, 95%CI = 0.80-1.83). Taking into account the effect of
      ethnicity, the LRP5 Ala1330Val polymorphism was not associated with the risk of
      fracture in Asians or Caucasians. The results of the current meta-analysis
      indicate that the LRP5 Ala1330Val polymorphism may not be correlated with
      fracture susceptibility. 

PMID- 27051031
TI  - Genomic ancestry evaluated by ancestry-informative markers in patients with
      sickle cell disease.
AB  - The beta(s) mutation is responsible for the most aggressive form of sickle cell
      disease, has a predominantly African origin, and arrived in Brazil through the
      slave trade. However, the Brazilian population is highly miscegenated,
      underscoring the importance of ancestry-informative markers (AIMs) for the
      identification of the genetic structure of a population. In this study, we have
      estimated the genetic contributions of various ethnicities in individuals with
      sickle cell disease in the microregion of Jequie, Bahia, in Brazil, by using
      AIMs, and compared the findings to those from a phenotypic characterization.
      Eight AIMs were analyzed: AT3 (rs3138521), DRD2 (rs1079598), APO (rs3138522),
      PV92, Sb19.3 (rs3138524), CKM (rs4884), LPL (rs285), and CCR5Delta32 (rs333).
      Samples were subjected to polymerase chain reaction (PCR) and PCR-restriction
      fragment length polymorphism. The amplified products were electrophoresed on
      agarose gels, and the data were statistically analyzed using Genepop, FSTAT 2.9,
      and Admix3. Phenotypic classification showed a high frequency of mulattos  (85%)
      in the Brazilian population; however, ancestry-informative markers indicated that
      44, 42, and 11% of the population had European, African, and native American
      ancestries, respectively. The phenotypic classification is justified as a
      complementary method for the characterization of the genetic ancestry in patients
      with sickle cell disease, as it confirms the molecular findings regarding
      ancestry. 

PMID- 27051032
TI  - Large-scale tissue-specific and temporal gene expression profiles in Pengze
      crucian carp.
AB  - In the present study, the tissue-specific and temporal gene expression profiles
      of four catalogues of gonadal development-related genes (sex differentiation
      related, steroid receptor, steroidogenic, and structural genes) were detected in
      nine tissues and during 11 successive developmental stages in the Pengze crucian
      carp (Pcc) (a triploid mono-female gynogenic fish). The results showed that these
      target genes exhibited overlapping distributions in various tissues, with the
      exception of Pcc-vasa and Pcc-cyp17a1. Gene expression profiling of the
      developmental stages showed that all of the target genes simultaneously reached
      peak expression levels at 40 and 48 days post hatching (dph). Both 40 and 48 dph
      appeared to be two key time points associated with the process of Pcc gonadal
      development. These data will provide a clear understanding of gene expression
      patterns associated with the gonadal development-related genes of this gynogenic
      teleost. 

PMID- 27051033
TI  - Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea
      virus samples obtained from farms in Gansu, China.
AB  - Porcine epidemic diarrhea poses significant sanitation problems in the porcine
      industry, and has negatively affected the economy in recent years. In this study,
      48 fecal specimens were collected from piglets from four intensive swine farms
      located in the Gansu Province of China. The molecular diversity and phylogenetic
      relationships between porcine epidemic diarrhea viruses (PEDV) prevalent in Gansu
      were probed, and the resultant proteins were characterized. Sequence analysis of
      the spike protein (S) genes showed that each specimen had unique characteristics,
      and that the PEDV1/S/4 strain could be differentiated from the others via a
      unique mutation of the S gene. The phylogeny of S glycoprotein showed that all
      strains were clustered into two major groups. The four Gansu PEDV field strains
      were characterized into different groups; this finding was consistent with the
      results of the protein characterization prediction. This analysis additionally
      revealed the unique characteristics of each specimen. The results of this study
      could be used to elucidate the prevalence of PEDV and contribute to the
      prevention of PEDV in Gansu. 

PMID- 27051034
TI  - Phenotypic characteristics for discrimination between advanced genotypes of
      Brachiaria ruziziensis.
AB  - The aim of this study was to use multivariate methods and Pearson and partial
      correlations to disregard phenotypic characteristics that contribute little to
      differentiation between Brachiaria ruziziensis genotypes. Eighty-one genotypes of
      B. ruziziensis were assessed in completely randomized blocks with three
      replications. Ten phenotypic characteristics were assessed: plant height, leaf
      length, leaf width, sheath length, length of the flower stem, length of the
      inflorescence axis, number of racemes per inflorescence, length of the basal
      raceme, number of spikelets per basal raceme, and width of the rachis. The best
      traits for differentiation between genotypes were determined by assessing
      relative contribution to diversity, canonical variables, as well as Pearson and
      partial correlations. Four canonical variables were found to account for 57% of
      the overall variation, while plant height, sheath length, and number of racemes
      per inflorescence were considered traits that could potentially be disregarded in
      future assessments. 

PMID- 27051035
TI  - Molecular markers located on the DGAT1, CAST, and LEPR genes and their
      associations with milk production and fertility traits in Holstein cattle.
AB  - The objective of the present study was to investigate single nucleotide
      polymorphisms (SNPs) located in three candidate genes previously reported to have
      effects on fertility and milk production traits in a population of 123 Holstein
      cows. The milk production traits evaluated included lifetime averages of milk
      yield, protein concentration, and fat concentration. Fertility traits evaluated
      included lifetime averages of services per conception and days-open. Candidate
      genes included those encoding diacylglycerol acyltransferase (DGAT1), leptin
      receptor (LEPR), and calpastatin (CAST). A total of 60 SNPs were selected (20 per
      gene) at equidistant locations on each candidate gene to identify potential
      linkage with causative mutations. Four SNPs were identified as being
      significantly associated with the evaluated fertility traits. Specifically, SNPs
      rs109663724 and rs137673193 were significantly associated with lifetime average
      days-open, while rs109663724 and rs135560721 were significantly associated with
      lifetime average number of services per conception. Five SNP (rs109663724,
      rs132699547, rs135423283, rs135576599, and rs13675432) were significantly
      associated with lifetime averages of milk protein concentration and milk fat
      concentration, with only one SNP (rs109663724) being significantly associated
      with the average lifetime milk yield. Although multiple SNPs were identified in
      the current study as being significantly associated with milk production and
      fertility traits, it is essential that these SNPs are validated in larger
      populations, under more diverse environments, and that additional SNPs and
      candidate genes are evaluated prior to their implementation into selection
      strategies. 

PMID- 27051036
TI  - APOA5 polymorphisms associated with lipid metabolism in Brazilian children and
      adolescents.
AB  - Single nucleotide polymorphisms in the APOA5 gene have been studied for their
      association with metabolic syndrome. Thus, elucidating the effect of the
      mechanism involved in APOA5 gene polymorphisms on lipid metabolism is of great
      importance. In this study we aimed to determine the allelic and genotypic
      frequencies of -1131T>C, Ser19Trp, and intergenic APOA4/A5 and to evaluate the
      association between these variants with plasma lipid levels in children and
      adolescents from Brazil. This study included 524 healthy children and adolescents
      from Mother and Child Hospital in Recife, Pernambuco, Brazil. Data were obtained
      on medical history, drug intake, lifestyle variables, and demography. DNA from
      collected samples was extracted and genotyped for the three polymorphisms. In
      this studied population, triglycerides and very low-density protein levels were
      significantly high in subjects carrying the 19WW genotype (P < 0.001),
      demonstrating the presence of this genetic risk factor in children and
      adolescents. 

PMID- 27051037
TI  - Selection for wide adaptability and high phenotypic stability of Brazilian
      soybean genotypes.
AB  - Advances in genetic enhancement techniques have led to an increase in soybean
      production. Thus, soybean is currently one the most economically important
      cultured species worldwide. The objectives of the present study were to study the
      interaction of soybean genotypes per environment in terms of grain productivity
      and to evaluate their phenotypic adaptability and stability, with the final aim
      of selecting lineages with high productivity, wide adaptability, and high
      stability. Seven soybean genotypes, consisting of five lineages developed by the
      soybean genetic enhancement program of the Universidade Federal de Uberlandia
      (Brazil) and two controls, were evaluated during several annual cycles in seven
      different environments. A randomized complete block design (RCBD) with three
      replicates was adopted in each site. This study followed the methodology proposed
      by Eberhart and Russel and Lin and Binns, with modifications by Carneiro, and the
      AMMI (additive main effects and multiplicative interaction model) analysis. The
      average productivity of soybean cultivars in the trials was 2739.26 kg/ha. The
      L01V13 genotype and the UFUS Guarani cultivar had wide adaptation according to
      the methodology proposed by Eberhart and Russel and Lin and Binns, with
      modifications by Carneiro. When analyzed with the AMMI model, the UFUS Guarani
      cultivar showed high stability. In general, the methodologies studied are
      complementary and, when used together, increase the reliability of the
      classification, providing support for the use of specific soybean cultivars in
      different environments. 

PMID- 27051038
TI  - Association between ERCC1 and ERCC2 gene polymorphisms and susceptibility to
      pancreatic cancer.
AB  - We conducted a study to investigate the association between ERCC1 (rs3212986) and
      ERCC2 (rs13181) gene polymorphisms and the risk of pancreatic cancer in a Chinese
      population. A total of 217 pancreatic cancer patients and 244 control subjects
      were recruited from the Nuclear Industry 215 Hospital of Shaanxi Province between
      February 2013 and December 2014. Genomic DNA was extracted from peripheral blood
      samples using a TIANamp Blood DNA Kit (Tiangen, Beijing, China) according to the
      manufacturer's instructions. The ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms
      were genotyped by polymerase chain reaction-restriction fragment length of
      polymorphism. Unconditional logistic regression analyses showed that subjects
      with the CC genotype of ERCC1 rs3212986 were susceptible to the development of
      pancreatic cancer when compared with subjects with the AA genotype (OR = 2.57,
      95%CI = 1.34-5.02). The ERCC1 rs3212986 gene polymorphism was associated with
      increased risk of pancreatic cancer in the dominant (OR = 1.54, 95%CI = 1.05
      2.28) and recessive (OR = 2.22, 95%CI = 1.20-4.19) models. However, no
      significant difference was found between the ERCC2 rs13181 polymorphism and the
      risk of pancreatic cancer in the codominant, dominant, and recessive models. We
      suggest that the ERCC1 rs3212986 polymorphism increases susceptibility to
      pancreatic cancer in the codominant, dominant, and recessive models, although
      further studies are needed to confirm our findings. 

PMID- 27051039
TI  - Expression of human papillomavirus E6 and E7 oncoprotein mRNA in women with low
      grade squamous intraepithelial lesions or less.
AB  - We verified the prevalence of human papillomavirus (HPV) E6/E7 protein mRNA
      expression in patients with low-grade squamous intraepithelial lesions (LSILs)
      and negative cervicovaginal cytology. To investigate the relationship between
      mRNA expression and viral infection type, we assessed genotyping in single
      infections. Samples from 825 women were submitted to the E6/E7 survey. We noticed
      a larger percentage of E6/E7 mRNA expression in the atypical squamous cells of
      undetermined significance (ASC-US) and LSIL cytologies. Negative results of mRNA
      expression were in accordance with negative cytologies. In positive cases, the
      infection by a single HPV type was most common, with type 16 being most
      prevalent. The expression of mRNA was most prevalent in ASC-US and LSIL
      cytologies, compared with the negative cytology. The infection by a HPV type was
      more frequent in cases of positive expression, with HPV type 16 being found most
      frequently. Patients with LSIL cytologies had a higher percentage of multiple
      infections. 

PMID- 27051040
TI  - Correlation of androgen receptor and SRD5A2 gene mutations with pediatric
      hypospadias in 46, XY DSD children.
AB  - We performed an exploratory study by analyzing the correlation of 46, XY
      disorders of sex development (46, XY DSD) with androgen receptor (AR) and steroid
      5alpha-reductase-2 (SRD5A2) gene mutations and a safety analysis of
      dihydrotestosterone (DHT) gel treatment for pediatric micropenis. We collected
      samples from 76 pediatric patients with 46, XY DSD and 50 healthy adult men with
      normal fertility as the control group. The pediatric patients were treated with
      DHT gel (0.1-0.3 mg/kg/day) for three to six months. The extended penis length,
      testicular volume, and multiple blood parameters were collected before treatment
      and one, three, and six months after treatment. Of the 76 cases with 46, XY DSD,
      31.58% had hypospadias with micropenis and 6.58% had male pseudohermaphroditism.
      Through AR gene screening, it was found that 14 patients had AR point mutations
      and 22 patients had SRD5A2 mutations. After treatment with DHT, the penis length
      of the patients significantly improved after one, three, and six months of
      treatment, with longer treatment times resulting in greater improvement. Before
      treatment with DHT, the average serum DHT value of patients with 46, XY DSD was
      24.29 pg/mL. After one, three, and six months of treatment, this value increased
      to 430.71, 328.9, and 323.6 pg/mL, respectively. We conclude that for pediatric
      patients who have male hermaphroditism or hypospadias with micropenis, AR and
      SRD5A2 gene mutation detection should be performed. Local application of DHT gel
      can promote penis growth effectively without systemic adverse reactions. 

PMID- 27051041
TI  - Can we measure patients' perception during dental impressions? The Burdens in
      Dental Impression-Making Questionnaire - BiDIM-Q.
AB  - PURPOSE: To develop a reliable and valid instrument for the comprehensive
      assessment of patients' burdens during dental impression making, the Burdens in
      Dental Impression Making Questionnaire, BiDIM-Q. MATERIALS: The item pool was
      generated in a convenience sample of 20 prosthodontic patients using semi
      structured face-to-face interviews. The final instrument was tested in 145
      consecutively recruited patients, and psychometric properties of the BiDIM-Q were
      determined. Four different impression materials were used according to the
      manufacturers' instructions and indications: alginate, c-silicone,
      polyvinylsiloxane, and polyether. RESULTS: The final BiDIM-Q consisting of 12
      items showed sufficient reliability, indicated by Cronbach's alpha of .82 and an
      average inter-item correlation of .29. Validity was supported by Pearson
      correlation coefficients for the correlation between the instrument's total score
      with the patients' overall satisfaction rating (r=.63), and by the correlation
      matrix for the correlations of the patients' perceptions with the practitioners'
      satisfaction ratings. Overall, patient perceived burdens were low with highest
      burdens observed when using polyether in partially dentate patients for pick-up
      impressions, while lowest burdens were reported when using c-silicone for
      impressions of edentulous jaws. CONCLUSION: The BiDIM-Q is a reliable and valid
      tool for assessing patient-based process-related quality of care in dentistry
      allowing a deeper insight into patients' perspective during dental impression
      making.

PMID- 27051042
TI  - Learning from the "tsunami" of immune checkpoint inhibitors in 2015.
AB  - 2015 was marked by the tsunami of immune checkpoint inhibitors revealed by
      numerous FDA approvals, publications and abstracts in relation with these drugs
      in different cancers and settings. First, we reported all new indications of anti
      CTLA4 and anti-PD1 approved by the FDA, the positive clinical trials published
      and the abstracts with promising results at important scientific meetings during
      2015. Then, we discussed different critical issues of these new agents going from
      their predictive factors, combination therapies, tumor response patterns,
      efficacy in particular settings, side effect management to cost and economic
      burden. 

PMID- 27051043
TI  - Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection
      in an Indonesian population.
AB  - Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence
      Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen
      presentation to CD4(+) helper T cells and influences the outcome of HBV
      infection. To investigate the influence of HLA-DP variants on the outcome of HBV
      infection in an Indonesian population where it has the third-highest prevalence
      of HBV infection worldwide, we performed a case-control study of 686
      participants, including patients with HBV-related advanced or nonadvanced liver
      disease, patients with spontaneously resolved HBV, and healthy controls. Single
      nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535,
      and rs228388) were genotyped using real-time TaqMan(r) genotyping assays. Because
      rs2281388 deviated from Hardy-Weinberg equilibrium, it was excluded from
      subsequent analyses. The results of logistic regression analyses showed that the
      HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV
      infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52-0.96,
      P=0.026, additive genetic model; OR 0.60, 95% CI 0.38-0.96, P=0.033, dominant
      genetic model). The HLA-DPA1 rs3077 variant was associated with a protective
      effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41
      0.98, P=0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021
      variant was not associated with the outcome of HBV infection, including
      susceptibility, spontaneously resolved, or disease progression. Combinations of
      haplotype markers were also associated with HBV susceptibility (CA for rs3077
      rs9277535, OR 0.57, 95% CI 0.36-0.92, P=0.021; GA for rs3135021-rs9277535, OR
      0.56, 95% CI 0.36-0.86, P=0.0087). In conclusion, these findings confirm that HLA
      DPA1/DPB1 variants were associated with the outcomes of HBV infection in an
      Indonesian population.

PMID- 27051044
TI  - Molecular epidemiology of canine picornavirus in Hong Kong and Dubai and proposal
      of a novel genus in Picornaviridae.
AB  - Previously, we reported the discovery of a novel canine picornavirus (CanPV) in
      the fecal sample of a dog. In this molecular epidemiology study, CanPV was
      detected in 15 (1.11%) of 1347 canine fecal samples from Hong Kong and one
      (0.76%) of 131 canine fecal samples from Dubai, with viral loads 1.06*10(3) to
      6.64*10(6) copies/ml. Complete genome sequencing and phylogenetic analysis showed
      that CanPV was clustered with feline picornavirus (FePV), bat picornavirus
      (BatPV) 1 to 3, Ia io picornavirus 1 (IaioPV1) and bovine picornavirus (BoPV),
      and this cluster was most closely related to the genera Enterovirus and
      Sapelovirus. The Ka/Ks ratios of all the coding regions were <0.1. According to
      the definition of the Picornavirus Study Group of ICTV, CanPV, FePV, BatPV 1 to
      3, IaioPV1 and BoPV should constitute a novel genus in Picornaviridae. BEAST
      analysis showed that this genus diverged from its most closely related genus,
      Sapelovirus, about 49 years ago.

PMID- 27051045
TI  - Polymorphisms in sodium taurocholate cotransporting polypeptide are not
      associated with hepatitis B virus clearance in Chinese Tibetans and Uygurs.
AB  - An association between polymorphisms in the sodium taurocholate cotransporting
      polypeptide (NTCP) and the natural course of hepatitis B virus (HBV) infection in
      the Chinese Han population has been noted. However, it is not known whether these
      polymorphisms are associated with the risk of developing chronic HBV infection in
      other racial or ethnic populations. Accordingly, we conducted a candidate single
      nucleotide polymorphism (SNP) association study in Tibetan and Uygur HBV-infected
      patients. A total of 1302 subjects including 871 Tibetans and 431 Uygurs were
      recruited. According to their serological and clinical characteristics, each
      ethnic group was divided into two groups comprising spontaneous clearance
      individuals and persistently infected patients. Three SNPs were genotyped by a
      high resolution melting curve methodology. Among the SNPs, rs2296651 exhibited a
      minor allele frequency of <0.01. The frequency of allele A at rs4646287 was much
      higher in Tibetans (9.4% for Tibetans and 4.6% for Uygurs, p<0.001) than in
      Uygurs, but the frequency of allele A at rs7154439 was the opposite (15.7% for
      Tibetans and 20.5% for Uygurs, p=0.002). Irrespective of race, no significant
      differences in the frequency distributions of the three SNP alleles or genotypes
      were observed between the case and clearance groups. Moreover, none of the NTCP
      haplotypes were statistically different between the two groups. Data from the
      Tibetan patients could be grouped by HBeAg status, viral load and HBV genotype;
      however, no significant differences were found in the SNP genotype distribution
      for each characteristic. In conclusion, the NTCP polymorphisms we identified
      tended to be ethnicity-dependent. For Tibetans and Uygurs, no association of the
      three SNPs (rs7154439, rs4646287 and rs2296651) and their haplotypes with HBV
      chronicity was observed. Examination of SNPs in NTCP for their specific
      associations with the course of HBV infection in other ethnic minority groups is
      now required.

PMID- 27051046
TI  - Genetic characterization of a densovirus isolated from great tit (Parus major) in
      China.
AB  - During a study of ornithophilous viruses in China, a new densovirus (DNV) was
      isolated from the lung tissue of Parus major (PmDNV-JL). The complete genome of
      PmDNV-JL was cloned and sequenced. Five open reading frames (ORFs) were
      identified in the 5166nt sequence, on the basis of deduced amino acids. It was
      further shown that this virus caused cytopathic effects (CPE) in Feline kidney
      cells. The NS1 gene sequence of PmDNV-JL shares 70-99% nucleotide sequence
      identity with isolates of the Blattella germanica densovirus (BgDNV) and BgDNV
      like virus. Phylogenetic analysis indicated that the predicted amino acid
      sequences of capsid (VP) and non-structural domain (NS1) of PmDNV-JL clustered
      with the BgDNV and were similar to BgDNV-HB within the genus Densovirus.

PMID- 27051047
TI  - Phylogenetic analysis of a newfound bat-borne hantavirus supports a
      laurasiatherian host association for ancestral mammalian hantaviruses.
AB  - Until recently, hantaviruses (family Bunyaviridae) were believed to originate
      from rodent reservoirs. However, genetically distinct hantaviruses were lately
      found in shrews and moles, as well as in bats from Africa and Asia. Bats (order
      Chiroptera) are considered important reservoir hosts for emerging human
      pathogens. Here, we report on the identification of a novel hantavirus,
      provisionally named Makokou virus (MAKV), in Noack's Roundleaf Bat (Hipposideros
      ruber) in Gabon, Central Africa. Phylogenetic analysis of the genomic l-segment
      showed that MAKV was the most closely related to other bat-borne hantaviruses and
      shared a most recent common ancestor with the Asian hantaviruses Xuan Son and
      Laibin. Breakdown of the virus load in a bat animal showed that MAKV resembles
      rodent-borne hantaviruses in its organ distribution in that it predominantly
      occurred in the spleen and kidney; this provides a first insight into the
      infection pattern of bat-borne hantaviruses. Ancestral state reconstruction based
      on a tree of l gene sequences of all relevant hantavirus lineages was combined
      with phylogenetic fossil host hypothesis testing, leading to a statistically
      significant rejection of the mammalian superorder Euarchontoglires (including
      rodents) but not the superorder Laurasiatheria (including shrews, moles, and
      bats) as potential hosts of ancestral hantaviruses at most basal tree nodes. Our
      data supports the emerging concept of bats as previously overlooked hantavirus
      reservoir hosts.

PMID- 27051048
TI  - Second-line Intraperitoneal Platinum-based Therapy Leads to an Increase in Second
      line Progression-free Survival for Epithelial Ovarian Cancer.
AB  - OBJECTIVE: Only 3% of patients with epithelial ovarian cancer (EOC) have a longer
      treatment-free interval (TFI) after second-line intravenous (IV) platinum
      chemotherapy than with frontline IV therapy. We sought to examine what impact
      second-line combination IV/intraperitoneal (IV/IP) platinum therapy might have on
      the ratio of second-line to first-line TFI in patients treated with second-line
      IP platinum chemotherapy for first recurrence after front-line IV therapy.
      METHODS: A retrospective analysis of women who received combination platinum
      based IV/IP chemotherapy for recurrent EOC between January 2005 and March 2011
      was conducted. Patients were identified from the tumor registry, and office
      records from a large gynecologic oncology practice and patient records were
      reviewed. The first and second TFIs were defined as the time from the end of
      previous platinum-based therapy to the start of next therapy. RESULTS: Twenty
      five women received IV/IP chemotherapy for their first EOC recurrence after IV
      chemotherapy. In 10 patients (40%), we observed a longer TFI after IV/IP
      chemotherapy than after primary IV chemotherapy. For these 10 patients, the
      median TFI for primary response was 22 months (range, 15-28), whereas median TFI
      after IV/IP chemotherapy for recurrent disease was 37 months (range, 12-61).
      CONCLUSIONS: For EOC patients with limited peritoneal recurrence, 40% of patients
      had a second-line IP-platinum TFI that exceeded their frontline IV-platinum TFI
      compared to published data. These data support the use of IV/IP chemotherapy as a
      treatment for recurrence.

PMID- 27051049
TI  - Alteration of Human Papillomavirus Type 16 Genetic and Epigenetic Profiles in
      Cervical Cancer Patients Is Indicative of Poor Disease Prognosis: A Cohort
      Analysis.
AB  - OBJECTIVE: Aim of this study was to assess the changes in genetic and epigenetic
      profiles of human papillomavirus type 16 (HPV16), if any, in primary cervical
      cancer (CaCx) and corresponding plasma before and after therapy for possible
      prognostic evaluation. METHODS: The genetic (integration status) and epigenetic
      (methylation of enhancer, early promoter, and late promoter sequences) profiles
      of HPV16 were analyzed in pretherapy CaCx (n = 46), corresponding plasma,
      posttherapy cervical swabs (n = 39), and corresponding plasma from a single
      patient cohort. Quantitative viral load was also measured in these HPV16-positive
      primary CaCx and posttherapy cervical swabs. RESULTS: Presence of HPV16 in the
      patients' plasma before/after therapy was significantly (P = 0.03) associated
      with higher viral load in the primary tumor site. Human papillomavirus type 16
      integration and hypomethylation of the early (14 of 29, Z = 4.47, P < 0.01) and
      late promoters (20 of 29, Z = 3.74, P < 0.01) were more prevalent in the plasma
      than the corresponding pretherapy CaCx samples. However, the dissimilarity in
      integration status (5 of 24) was less evident between posttherapy cervical swabs
      and corresponding plasma, although hypomethylation of the early promoter and
      hypermethylation of the late promoter (8 of 24, Z = 2.6, P < 0.01) was seen in
      posttherapy plasma samples. Whereas in the posttherapy swabs, integrated (22 of
      29) or mixed (7 of 29) form of HPV16 prevailed with hypomethylation of the
      enhancer (6 of 29, Z = 2.0, P < 0.05) and late promoter (18 of 29, Z = 4.4, P <
      0.01) compared with the corresponding primary tumors. The patients having high
      HPV16 copy number in pretherapy and posttherapy cervical lesions and
      hypomethylation of early promoter/late promoter in the corresponding plasma
      showed increased disease recurrence with distant metastases. CONCLUSIONS: The
      genetic-epigenetic profile of HPV16 in pretherapy/posttherapy CaCx samples showed
      significant association with disease prognosis.

PMID- 27051050
TI  - Substance P Promotes the Progression of Endometrial Adenocarcinoma.
AB  - OBJECTIVES: It has been demonstrated that substance P (SP) promotes while
      neurokinin-1 receptor (NK-1R) antagonist inhibits the proliferation of several
      human cancer cells. Currently, it is still unknown whether such actions exist in
      human endometrial carcinoma. This study aimed to explore the role of SP/NK-1R
      signaling in the progression of endometrial adenocarcinoma. MATERIALS AND
      METHODS: The expression levels of SP and NK-1R in endometrial adenocarcinoma
      tissues and Ishikawa cell line were detected by real-time quantitative PCR and
      Western blot analysis. The effects of SP on Ishikawa cells proliferation and
      invasion were analyzed using MTT assay and transwell matrigel invasion assay,
      respectively. The expression levels of matrix metalloproteinase 9 (MMP-9) and
      vascular endothelial growth factor C (VEGF-C) in Ishikawa cells after
      administration of SP were detected by real-time quantitative RCR and Western blot
      analysis. RESULTS: The expression levels of SP and NK-1R were significantly
      higher in endometrial adenocarcinoma tissues and Ishikawa cells than in normal
      endometrium. Substance P significantly enhanced the proliferation and invasion of
      Ishikawa cells. In addition, SP induced the expression of MMP-9 and VEGF-C in
      Ishikawa cells, whereas NK-1R antagonist inhibited these effects. CONCLUSIONS:
      Substance P plays an important role in the development of endometrial carcinoma
      by inducing the expression of MMP-9 and VEGF-C and promoting cancer cell
      proliferation and metastasis, which can be blocked by NK-1R antagonist.

PMID- 27051051
TI  - Signs and Symptoms of Venous Thromboembolism and Survival Outcome of Endometrial
      Cancer.
AB  - OBJECTIVE: This study aimed to evaluate if the presence of venous thromboembolism
      (VTE) diagnosed with subjective and objective measurements correlates with the
      survival outcome in patients with endometrial cancer. METHODS: A retrospective
      study was conducted on patients with endometrial cancer who developed VTE between
      cancer diagnosis and follow-up from 1999 to 2013. Disease-specific survival after
      VTE diagnosis was evaluated according to VTE symptoms and vital signs. RESULTS:
      Among 827 endometrial cancer cases during the study period, there were 72 (8.7%)
      patients with VTE identified (pulmonary embolism [PE] with or without deep vein
      thrombosis [DVT], n = 34; and DVT alone n = 38). In the PE group, decreased
      disease-specific survival after the diagnosis of VTE was associated with fatigue,
      systolic blood pressure (BP) less than 120 mm Hg, diastolic BP less than 70 mm
      Hg, and a heart rate 90 beats per minute or greater (all, P < 0.05) in a
      univariate analysis. Symptomatic PE was associated with decreased survival as
      compared to asymptomatic PE (2-year rate; 23.1% vs 77.8%, P < 0.01). In a
      multivariate analysis controlling for symptoms of VTE, signs, and tumor factors,
      a diastolic BP less than 70 mm Hg (adjusted-hazard ratio [HR], 10.0; 95%
      confidence interval, 2.70-37.1; P < 0.01) and HR greater than 90 beats per minute
      (adjusted-HR, 8.06; 95% confidence interval, 2.36-27.5; P < 0.01) remained as
      independent prognostic factors for decreased disease-specific survival after PE
      diagnosis. Patients with PE presenting with low diastolic BP and high heart rate
      resulted in a dismal survival outcome (diastolic BP < 70 mm Hg/heart rate >= 90
      beats per minute vs diastolic BP >= 70 mm Hg/heart rate < 90 beats per minute; 0%
      vs 85.7%, P < 0.01). In the group of patients with DVT alone, no signs or
      symptoms correlated with survival outcome (all, P > 0.05). CONCLUSIONS: Our
      results suggested that both signs and symptoms of PE are important consideration
      in the management of patients with endometrial cancer with PE.

PMID- 27051052
TI  - Minimal Macroscopic Residual Disease (0.1-1 cm). Is It Still a Surgical Goal in
      Advanced Ovarian Cancer?
AB  - OBJECTIVE: The objective of this review was to try to determine by searching in
      the literature what is the survival in patients with advanced ovarian cancer
      after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1-10
      mm). Additionally, this review aimed to explore the survival in patients with
      residual disease from 0.1 to 0.5 cm. METHODS: A retrospective search was
      accomplished in the PubMed database looking for all English-language articles
      published between January 1, 2007 and December 31, 2014, under the following
      search strategy: "ovarian cancer and cytoreduction" or "ovarian cancer and phase
      III trial". We selected those articles that contain information on both
      percentage of MMRD (0.1-1 cm) and median overall survival (OS) in this subset of
      patients with stage III to stage IV ovarian cancer after primary debulking
      surgery. RESULTS: Thirteen publications were obtained including information of a
      total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand
      thirty-seven patients (42%) had MMRD after the primary debulking (0.1-1 cm).
      Median overall survival in patients with MMRD was 40 months and disease-free
      survival (DFS) was 16 months. This group of patients obtained an advantage of 10
      months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the
      group with suboptimal debulking (P < 0.001). Compared with the group of complete
      resection, patients with minimal macroscopic residuum showed a significant
      inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40
      m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm
      reached a median survival of 53 months. CONCLUSIONS: Patients with ovarian cancer
      with MMRD after primary surgery obtain a modest but significant advantage in
      survival (10 months) over suboptimal patients. Patients with macroscopic residual
      disease (0.1-0.5 cm) obtain a better survival (53 months) than those with more
      than 0.5 to 1 cm. We propose that they should be classified as a different
      prognostic group.

PMID- 27051053
TI  - Impact of Clinical Genetics Attendance at a Gynecologic Oncology Tumor Board on
      Referrals for Genetic Counseling and BRCA Mutation Testing.
AB  - OBJECTIVES: The objectives of this work were to determine the proportion of
      eligible patients with ovarian cancer discussed at a gynecologic oncology tumor
      board who were referred for counseling and BRCA mutation testing; to compare
      referral rates before genetics attendance at the tumor board to referral rates
      after genetics attendance; and to ascertain the proportions of women with
      germline BRCA mutations. MATERIALS AND METHODS: Eligible cases were identified
      from the minutes of the weekly Western Australian gynecologic oncology tumor
      board from July 1, 2013 to June 30, 2015.Patients with ovarian cancer who met
      eligibility criteria for genetics referral were identified and checked against
      the records of the genetic services database to ascertain whether a referral was
      received. Outcomes including attendance for counseling and results of mutation
      testing were analyzed. RESULTS: Two hundred sixty-one patients were eligible for
      referral during the 24-month study period. One hundred six patients (40.6%) were
      referred for counseling and germline mutation testing. Of the eligible patients,
      26.7% were referred in the 12 months before genetics attendance at the tumor
      board compared to 51.7% of the eligible patients in the 12 months after genetics
      attendance (P <= 0.0001). Ninety-seven patients were offered BRCA mutation
      testing, and 73 underwent testing with 65 results reported to date. Twenty-two
      patients (33.8 %) tested positive for a germline BRCA mutation. CONCLUSIONS:
      Patients with ovarian cancer had a high rate of BRCA mutations. Attendance of a
      genetics service at a tumor board was associated with an improved rate of
      referral of patients for genetic counseling and BRCA mutation testing.

PMID- 27051054
TI  - Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical
      Staging for Endometrial Cancer.
AB  - OBJECTIVE: The aim of this study was to assess the role of intraoperative frozen
      section (FS) in guiding decision making for surgical staging of endometrioid
      endometrial cancer (EC). METHODS: Medical records were collected retrospectively
      on 112 patients with endometrioid EC, who underwent total hysterectomy and
      bilateral salpingo-oophorectomy at the University of Arizona Medical Center from
      January 1, 2010, to December 31, 2014. Only patients with endometrioid
      adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less
      than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise,
      surgical staging was performed with lymph node dissection. The FS results were
      compared with the permanent paraffin sections (PSs) to assess the diagnostic
      accuracy. RESULTS: The concordance rate of different variables between FS and PS
      in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112),
      respectively, with respecting to histological subtype, grade, myometrial
      invasion, and tumor size. Diagnostic accurate rate of combined risk factors
      deciding surgical staging at the time of FS was 95.5% (107/112), and the
      discordance rate of all risk factors considered between FS and PS was 4.5%,
      resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated.
      CONCLUSIONS: Despite nonideal FS evaluation, intraoperative FS diagnosis for EC
      is highly reliable by providing guidance for the intraoperative decisions of
      surgical staging at our institution, and such guidelines may be referenced by the
      institutions with sufficient gynecologic pathology expertise.

PMID- 27051055
TI  - Interval Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in
      First-Line Treatment for Advanced Ovarian Carcinoma: A Feasibility Study.
AB  - OBJECTIVES: We conducted a phase 2 trial to assess the feasibility of interval
      cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      with cisplatin in patients with stage III and IV pleural ovarian carcinoma in
      first-line treatment with no macroscopic residual disease after surgery. METHODS:
      Patients could be treated either with primary CS with HIPEC followed by 6
      conventional cycles of chemotherapy or with 3 or 4 cycles of neoadjuvant
      chemotherapy before CS with HIPEC and 3 postoperative chemotherapy cycles.
      Hyperthermic intraperitoneal chemotherapy was performed with cisplatin (50 mg/m)
      for 60 minutes, only in case of complete cytoreduction. RESULTS: Nineteen
      patients were included in the study, and they all underwent neoadjuvant
      chemotherapy before CS. Sixteen patients underwent complete CS with HIPEC. There
      was no mortality, and morbidity of CS with HIPEC was acceptable. The HIPEC
      procedure did not prevent the administration of the standard first-line
      treatment. In the 16 patients who underwent CS with HIPEC, the outcomes were very
      good. CONCLUSION: Our study shows an acceptable toxicity of adding HIPEC to the
      standard first-line treatment in patients with stage III ovarian carcinoma
      treated with interval CS. Further studies are needed to confirm the role of HIPEC
      in the treatment of ovarian carcinoma.

PMID- 27051056
TI  - Proteasome Inhibitor MG132 Enhances Sensitivity to Cisplatin on Ovarian Carcinoma
      Cells In Vitro and In Vivo.
AB  - BACKGROUND: Platinum-based combination chemotherapy after surgery is considered a
      standard treatment; therefore, any recent drug development should be new,
      effective, and low toxic, and should have a synergistic effect with platinum.
      This study aimed to observe the growth of SKOV3 cells after treatment with
      cisplatin by combining with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and
      to investigate the effect of the relationship between MG132 and cisplatin
      combination. MATERIALS AND METHODS: Cell growth was detected by methyl thiazolyl
      tetrazolium assay after treatment with MG132 at 0.5, 1.5, 2.5, 3.5, and 5.0
      MUg/mL concentrations for 24, 48, and 72 hours; with cisplatin at 1.0, 2.0, 3.0,
      4.0, and 5.0 MUg/mL concentrations; and with combination with MG132 at 1.5 MUg/mL
      for 24 hours. The apoptotic rates of cells were detected by a flow cytometer
      after cisplatin treatment at 1.0, 2.0, 3.0, and 4.0 MUg/mL concentrations and
      that combined with MG132 at 1.5 MUg/mL concentration for 12, 24, and 36 hours. A
      total of 20 BALB/c (nu/nu) female nude mice (age, 4-6 weeks; body weight, 17-19
      g) were divided into 4 groups: control, MG132, cisplatin, and combination groups.
      The expression of Caspase3 and Beclin1 was detected by Western blot analysis and
      reverse transcription-polymerase chain reaction after treatment with 3.0 MUg/mL
      of the cisplatin group and combined treatment with 1.5 MUg/mL of MG132 group for
      24 hours, respectively. RESULTS: Methyl thiazolyl tetrazolium assay demonstrated
      the inhibitory rates, and the flow cytometery showed that the apoptotic rates in
      the combination group were higher than those in the cisplatin group (P < 0.01).
      Western blot analysis and reverse transcription-polymerase chain reaction
      detected that Caspase3 and Beclin1 at a relative quantity in the combination
      group were higher than those in the cisplatin group (P < 0.05). CONCLUSIONS:
      MG132 has a synergistic antitumor effect by combining with cisplatin, and it is
      expected to be an effective antitumor drug for platinum-resistant refractory
      ovarian cancer.

PMID- 27051057
TI  - Does Routine Posttreatment PET/CT Add Value to the Care of Women With Locally
      Advanced Cervical Cancer?
AB  - OBJECTIVES: The aim of this study was to determine the necessary reduction in
      recurrence rate that would make postchemoradiation positron emission tomography
      (PET)/computed tomography (CT) to direct completion hysterectomy for locally
      advanced cervical cancer (LACC) cost-effective. METHODS: A decision model
      evaluated costs and recurrence rates of 2 posttreatment surveillance strategies
      in LACC: (1) routine surveillance without PET/CT and (2) PET/CT after 3 months to
      triage to completion hysterectomy. Incremental cost-effectiveness ratios were
      expressed in dollars per additional cancer recurrence avoided. Model parameters
      included expected rates of recurrence using each strategy, true- and false
      positive rates of posttreatment PET/CT, and major complications of completion
      hysterectomy. From published data, we modeled an LACC baseline recurrence rate of
      32%, PET/CT false-positive rate of 33%, and false-negative rate of 19%. We
      assumed that PET/CT revealed persistent local cervical cancer in 16% and
      progressive or distant disease in 6%. Costs of PET/CT, hysterectomy, and
      treatment for recurrence were based on Medicare reimbursements. A 50% salvage
      rate with hysterectomy was assumed and varied in sensitivity analysis. RESULTS:
      Routine use of PET/CT to direct completion hysterectomy was associated with a
      higher average cost ($16,579 vs $15,450) and a lower recurrence rate (26% vs
      32%). The incremental cost-effectiveness ratio of PET was $20,761 per recurrence
      prevented. When the probability of recurrence after hysterectomy dropped to 25%
      or less, PET/CT was a dominant strategy. CONCLUSIONS: Routine use of PET/CT to
      determine which patients may benefit from a completion hysterectomy after
      chemoradiation for LACC has the potential to be highly cost-effective.

PMID- 27051058
TI  - Methods Used in Economic Evaluations of Testing and Diagnosis for Ovarian Cancer:
      A Systematic Review.
AB  - OBJECTIVE: There are multiple tests available that can help diagnose ovarian
      cancer, and the cost-effective analysis of these diagnostic interventions is
      essential for making well-informed decisions regarding resource allocation. There
      are multiple factors that can impact on the conclusions drawn from economic
      evaluations including test accuracy, the impact of the testing pathway on patient
      costs and outcomes, and delays along the ovarian cancer test-treat pathway. The
      objective of this study was to evaluate how test accuracy, the choice of
      perspective, and delays along the testing and diagnostic pathway have been
      incorporated in economic evaluations of testing for ovarian cancer. METHODS: A
      systematic review of published literature was undertaken to identify economic
      evaluations (eg, cost-effectiveness, cost-utility analysis) focused on testing
      and diagnosis for ovarian cancer. RESULTS: Seven studies met the inclusion
      criteria. Six studies incorporated test accuracy and its impact on patients to
      some extent. Four studies adopted a societal perspective, but only one considered
      the costs incurred by patients on the testing and diagnosis pathway. Where delays
      on the testing pathway were incorporated into the analysis, these were frequently
      due to false-negative test results leading to delays in patients accessing
      treatment. Any anxiety that patients might experience as a result of a positive
      test was not considered in these studies. CONCLUSIONS: The impact on patients of
      receiving a positive test in terms of anxiety and the costs incurred by patients
      having to attend for testing and diagnosis are rarely considered. Delays along
      the testing and diagnosis pathway can have a major effect on patient outcomes,
      and it is important that these are acknowledged in economic evaluations focused
      on testing. Future economic analysis should incorporate these key determinants in
      order that diagnostic tests for ovarian cancer can be robustly evaluated.

PMID- 27051059
TI  - BAF250a Expression in Atypical Endometriosis and Endometriosis-Associated Ovarian
      Cancer.
AB  - BACKGROUND AND OBJECTIVE: Atypical endometriosis (AE) is thought to be a
      precursor lesion to the ovarian cancer subtypes associated with endometriosis,
      namely, endometrioid and clear cell carcinomas. ARID1A encodes a nuclear protein
      (BAF250a) governing chromatin remodeling, and mutations in ARID1A have been found
      in 30% to 50% of clear cell and endometrioid ovarian cancers. As BAF250a
      expression loss by immunohistochemistry (IHC) has been documented in the
      endometriosis precursor lesions closely associated with these ovarian cancers
      subtypes, our goal was to further study the association between BAF250a
      expression in cases of AE with and without an associated cancer. METHODS: Three
      separate databases were screened for suspected cases of AE. Based on a detailed
      review of the pathology reports, we selected cases likely to contain AE for slide
      review. After slide review, tissue blocks were recalled to perform IHC for
      BAF250a in the associated cancer, AE, or typical endometriosis when present.
      RESULTS: There were 35 cases of endometriosis-associated cancer and 8 cases of AE
      not associated with cancer. Atypical endometriosis was found on pathology review
      in 23 endometriosis-associated cancer cases (66%). In the 35 cancer cases,
      BAF250a IHC showed loss of expression in 14 cases. Atypical endometriosis was
      present in 10 of these cases, 6 of which showed BAF250a loss (60%). BAF250a loss
      was not observed in the 8 cases of AE not associated with cancer or in the
      contiguous AE of 13 cases, whereby BAF250a expression was retained in the
      associated cancer. CONCLUSIONS: BAF250a loss in AE is consistently associated
      with the development of BAF250a-negative endometriosis-associated cancers and
      appears to be an early event in most of these cases. This research provides
      additional evidence that in the absence of cancer, BAF250a expression should be
      evaluated as a biomarker of cancer risk in patients diagnosed with AE.

PMID- 27051060
TI  - Oncologic Outcomes of Stage IVB or Persistent or Recurrent Cervical Carcinoma
      Patients Treated With Chemotherapy at Siriraj Hospital: Thailand's Largest
      Tertiary Referral Center.
AB  - OBJECTIVES: To determine response rate and survival outcomes of chemotherapeutic
      treatment in stage IVB, persistent, or recurrent cervical carcinoma patients.
      METHODS: Medical records of stage IVB or persistent or recurrent cervical
      carcinoma patients who received chemotherapy from January 2006 to December 2013
      were retrospectively reviewed. Patients with neuroendocrine carcinoma and
      patients who received only 1 cycle of chemotherapy were excluded. The demographic
      data, tumor characteristics, chemotherapeutic agents, and response rate were
      reported. Factors associated with overall response rate from the first-round
      chemotherapeutic treatment were analyzed using chi test. Kaplan-Meier method and
      Cox proportional hazards model were used for survival analysis. RESULTS: Of 286
      cervical carcinoma patients, 47 patients had stage IVB and 239 patients had
      persistent or recurrent disease. One hundred sixty-nine patients (59.1%) had
      squamous cell carcinoma (SCC). A majority of disease sites (38.8%) had both local
      and distant metastases. Overall response rate for first-round chemotherapeutic
      treatment was 37.8%, with 23.1% of patients having a complete response and 14.7%
      of patients having a partial response. Regarding disease response, 32.2% of
      patients had stable disease and 30% had disease progression. Median overall
      survival (OS) and progression-free survival (PFS) for first-round
      chemotherapeutic treatment were 11.6 (range, 0.7-108.3) months and 5.6 (range,
      0.7-102.2) months, respectively. Patients with distant metastasis had a shorter
      OS duration with an adjusted hazard ratio (HR) of 1.78, 95% confidence interval
      (CI) of 1.09 to 2.90; P = 0.02. Patients with a body mass index of 25 kg/m or
      more had a longer PFS duration than those with a normal body mass index (adjusted
      HR, 0.72; 95% CI, 0.55-0.94; P = 0.018). Patients with non-SCC had a longer PFS
      duration than that of patients with SCC (adjusted HR, 0.77; 95% CI, 0.60-0.99; P
      = 0.041). CONCLUSIONS: Response rates, median PFS, and median OS of cervical
      cancer patients treated by chemotherapy in our center were rather high when
      compared with those of previous gynecologic oncology group studies.

PMID- 27051061
TI  - Comparison on radiographic progression for 5 years between juvenile onset
      ankylosing spondylitis and adult onset ankylosing spondylitis: an observational
      study of the Korean SpondyloArthropathy Registry (OSKAR) data.
AB  - OBJECTIVES: To evaluate differences in radiographic progression between adult
      onset ankylosing spondylitis (AoAS) and juvenile-onset ankylosing spondylitis
      (JoAS). METHODS: A total of 533 patients (418 patients with AoAS and 115 patients
      with JoAS) from the Observation Study of Korean spondyloArthropathy Registry
      (OSKAR) cohort were enrolled. All baseline OSKAR data were analysed in relation
      to disease onset and radiographic progression was analysed between the groups
      over 5 years. The modified Stoke AS Spinal Score (mSASSS) were used by two
      experienced radiologists. Clinical data were collected to investigate the
      associations between clinical factors and radiographic progression. Radiographic
      scores were compared using analysis of covariance model after adjusting for
      confounding factors. RESULTS: Inter-reader reliability for baseline mSASSS was
      very good. Inter-reader reliability for the changes in the mSASSS was also good.
      A significant difference in baseline mSASSS (mean +/- SD) unit was detected
      between the AoAS and JoAS groups (18.1+/-17.4 vs. 14.3+/-13.8, p=0.015). We
      assessed the change in mSASSS to confirm whether age at onset affected
      radiographic progression. A simple comparison revealed a significant difference
      between changes on the mSASSS (mean +/- SEM) between the JoAS and AoAS groups
      (1.75+/-0.71 vs. 3.77+/-0.56, p<0.001). After adjusting for multiple comparisons,
      change on the mSASSS remained lower in patients with JoAS than those with AoAS
      (0.28+/-1.33 vs. 4.08+/-0.62, p=0.016). CONCLUSIONS: Patients with JoAS had
      slower radiographic spinal damage progression over 5 years than those with AoAS.

PMID- 27051062
TI  - A prognostic tool to predict severe acute pancreatitis in pediatrics.
AB  - BACKGROUND/OBJECTIVES: Approximately 15-20% of pediatric patients with acute
      pancreatitis (AP) develop severe disease. Severity scoring tools were developed
      for adult patients, but have limitations when applied in children. We aimed to
      identify early predictors of severe acute pancreatitis (SAP) on hospital
      admission for early risk stratification of patients. METHODS: Retrospective
      review of AP admissions was conducted. The derivation cohort included cases at
      Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2013.
      Clinical data collected during the first 24 h of admission were analyzed and a
      predictive model was derived through statistical analysis. The performance of the
      model was evaluated in a validation cohort from 2 more institutions other than
      CCHMC. RESULTS: In the derivation cohort 19% of the 284 admissions were SAP. A
      generalized linear mixed effect model analysis revealed that lipase, albumin and
      white blood count (WBC) play a role in the development of SAP (area under the
      receiver operating curve (AUROC 0.76)). In the validation cohort of 165 AP cases,
      SAP ranged from 8 to 20% at the three institutions. Performance of the model in
      this cohort was comparable to the derivation model (AUROC 0.77). There were 369
      encounters in the combined derivation and validation pool (AUROC 0.76).
      CONCLUSIONS: The prognostic severity tool with 3 variables (lipase, albumin, and
      WBC) obtained within 24 h of admission can be applied to predict SAP in pediatric
      patients.

PMID- 27051063
TI  - Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important
      regulators of cardiac function.
AB  - Cellular metabolites, such as acyl-CoA, can modify proteins, leading to protein
      posttranslational modifications (PTMs). One such PTM is lysine succinylation,
      which is regulated by sirtuin 5 (SIRT5). Although numerous proteins are modified
      by lysine succinylation, the physiological significance of lysine succinylation
      and SIRT5 remains elusive. Here, by profiling acyl-CoA molecules in various mouse
      tissues, we have discovered that different tissues have different acyl-CoA
      profiles and that succinyl-CoA is the most abundant acyl-CoA molecule in the
      heart. This interesting observation has prompted us to examine protein lysine
      succinylation in different mouse tissues in the presence and absence of SIRT5.
      Protein lysine succinylation predominantly accumulates in the heart whenSirt5is
      deleted. Using proteomic studies, we have identified many cardiac proteins
      regulated by SIRT5. Our data suggest that ECHA, a protein involved in fatty acid
      oxidation, is a major enzyme that is regulated by SIRT5 and affects heart
      function.Sirt5knockout (KO) mice have lower ECHA activity, increased long-chain
      acyl-CoAs, and decreased ATP in the heart under fasting conditions.Sirt5KO mice
      develop hypertrophic cardiomyopathy, as evident from the increased heart weight
      relative to body weight, as well as reduced shortening and ejection fractions.
      These findings establish that regulating heart metabolism and function is a major
      physiological function of lysine succinylation and SIRT5. 

PMID- 27051064
TI  - Tracking brain arousal fluctuations with fMRI.
AB  - Changes in brain activity accompanying shifts in vigilance and arousal can
      interfere with the study of other intrinsic and task-evoked characteristics of
      brain function. However, the difficulty of tracking and modeling the arousal
      state during functional MRI (fMRI) typically precludes the assessment of arousal
      dependent influences on fMRI signals. Here we combine fMRI, electrophysiology,
      and the monitoring of eyelid behavior to demonstrate an approach for tracking
      continuous variations in arousal level from fMRI data. We first characterize the
      spatial distribution of fMRI signal fluctuations that track a measure of
      behavioral arousal; taking this pattern as a template, and using the local field
      potential as a simultaneous and independent measure of cortical activity, we
      observe that the time-varying expression level of this template in fMRI data
      provides a close approximation of electrophysiological arousal. We discuss the
      potential benefit of these findings for increasing the sensitivity of fMRI as a
      cognitive and clinical biomarker. 

PMID- 27051065
TI  - Asymmetric arginine dimethylation of RelA provides a repressive mark to modulate
      TNFalpha/NF-kappaB response.
AB  - Nuclear factor kappa B (NF-kappaB) is an inducible transcription factor that
      plays critical roles in immune and stress responses and is often implicated in
      pathologies, including chronic inflammation and cancer. Although much has been
      learned about NF-kappaB-activating pathways, the specific repression of NF-kappaB
      is far less well understood. Here we identified the type I protein arginine
      methyltransferase 1 (PRMT1) as a restrictive factor controlling TNFalpha-induced
      activation of NF-kappaB. PRMT1 forms a cellular complex with NF-kappaB through
      direct interaction with the Rel homology domain of RelA. We demonstrate that
      PRMT1 methylates RelA at evolutionary conserved R30, located in the DNA-binding
      L1 loop, which is a critical residue required for DNA binding. Asymmetric R30
      dimethylation inhibits the binding of RelA to DNA and represses NF-kappaB target
      genes in response to TNFalpha. Molecular dynamics simulations of the DNA-bound
      RelA:p50 predicted structural changes in RelA caused by R30 methylation or a
      mutation that interferes with the stability of the DNA-NF-kappaB complex. Our
      findings provide evidence for the asymmetric arginine dimethylation of RelA and
      unveil a unique mechanism controlling TNFalpha/NF-kappaB signaling. 

PMID- 27051066
TI  - Perceptual learning modifies the functional specializations of visual cortical
      areas.
AB  - Training can improve performance of perceptual tasks. This phenomenon, known as
      perceptual learning, is strongest for the trained task and stimulus, leading to a
      widely accepted assumption that the associated neuronal plasticity is restricted
      to brain circuits that mediate performance of the trained task. Nevertheless,
      learning does transfer to other tasks and stimuli, implying the presence of more
      widespread plasticity. Here, we trained human subjects to discriminate the
      direction of coherent motion stimuli. The behavioral learning effect
      substantially transferred to noisy motion stimuli. We used transcranial magnetic
      stimulation (TMS) and functional magnetic resonance imaging (fMRI) to investigate
      the neural mechanisms underlying the transfer of learning. The TMS experiment
      revealed dissociable, causal contributions of V3A (one of the visual areas in the
      extrastriate visual cortex) and MT+ (middle temporal/medial superior temporal
      cortex) to coherent and noisy motion processing. Surprisingly, the contribution
      of MT+ to noisy motion processing was replaced by V3A after perceptual training.
      The fMRI experiment complemented and corroborated the TMS finding. Multivariate
      pattern analysis showed that, before training, among visual cortical areas,
      coherent and noisy motion was decoded most accurately in V3A and MT+,
      respectively. After training, both kinds of motion were decoded most accurately
      in V3A. Our findings demonstrate that the effects of perceptual learning extend
      far beyond the retuning of specific neural populations for the trained stimuli.
      Learning could dramatically modify the inherent functional specializations of
      visual cortical areas and dynamically reweight their contributions to perceptual
      decisions based on their representational qualities. These neural changes might
      serve as the neural substrate for the transfer of perceptual learning.

PMID- 27051067
TI  - Direct imaging of magnetic field-driven transitions of skyrmion cluster states in
      FeGe nanodisks.
AB  - Magnetic skyrmion is a nanosized magnetic whirl with nontrivial topology, which
      is highly relevant for applications on future memory devices. To enable the
      applications, theoretical efforts have been made to understand the dynamics of
      individual skyrmions in magnetic nanostructures. However, directly imaging the
      evolution of highly geometrically confined individual skyrmions is challenging.
      Here, we report the magnetic field-driven dynamics of individual skyrmions in
      FeGe nanodisks with diameters on the order of several skyrmion sizes by using
      Lorentz transmission electron microscopy. In contrast to the conventional
      skyrmion lattice in bulk, a series of skyrmion cluster states with different
      geometrical configurations and the field-driven cascading phase transitions are
      identified at temperatures far below the magnetic transition temperature.
      Furthermore, a dynamics, namely the intermittent jumps between the neighboring
      skyrmion cluster states, is found at elevated temperatures, at which the thermal
      energy competes with the energy barrier between the skyrmion cluster states.

PMID- 27051068
TI  - Comparison of syncytiotrophoblast generated from human embryonic stem cells and
      from term placentas.
AB  - Human embryonic stem cells (ESCs) readily commit to the trophoblast lineage after
      exposure to bone morphogenetic protein-4 (BMP-4) and two small compounds, an
      activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83
      01/PD173074; BAP treatment). During differentiation, areas emerge within the
      colonies with the biochemical and morphological features of syncytiotrophoblast
      (STB). Relatively pure fractions of mononucleated cytotrophoblast (CTB) and
      larger syncytial sheets displaying the expected markers of STB can be obtained by
      differential filtration of dispersed colonies through nylon strainers. RNA-seq
      analysis of these fractions has allowed them to be compared with cytotrophoblasts
      isolated from term placentas before and after such cells had formed syncytia.
      Although it is clear from extensive gene marker analysis that both ESC- and
      placenta-derived syncytial cells are trophoblast, each with the potential to
      transport a wide range of solutes and synthesize placental hormones, their
      transcriptome profiles are sufficiently dissimilar to suggest that the two cell
      types have distinct pedigrees and represent functionally different kinds of STB.
      We propose that the STB generated from human ESCs represents the primitive
      syncytium encountered in early pregnancy soon after the human trophoblast invades
      into the uterine wall.

PMID- 27051070
TI  - Cognitive Function as a Mediator in the Relationship Between Physical Activity
      and Depression Status in Older Adults.
AB  - Previous research has found that increased physical activity may provide a
      protective effect on depression status; however, these studies do not account for
      cognitive function. This study's aim was to determine whether cognitive function
      mediates the association between physical activity depression status in older
      adults. Data from 501 older adults were used for this analysis. Physical activity
      had a significant protective effect on depression (OR = 0.761, 95% CI [0.65,
      0.89], p = .001). Adjusted analysis yielded an attenuated association (OR = 0.81,
      95% CI [0.69, 0.95], p = .01) with a significant interaction for physical
      activity and cognitive function (OR = 0.991, 95% CI [0.985, 0.997], p = .005).
      MoCA performance also had a significant mediating effect on the relationship
      between physical activity and depression status (p = .04). These findings suggest
      that cognitive function is associated with, and does mediate, the relationship
      between physical activity and depression status.

PMID- 27051069
TI  - Inflammatory and neuropathic cold allodynia are selectively mediated by the
      neurotrophic factor receptor GFRalpha3.
AB  - Tissue injury prompts the release of a number of proalgesic molecules that induce
      acute and chronic pain by sensitizing pain-sensing neurons (nociceptors) to heat
      and mechanical stimuli. In contrast, many proalgesics have no effect on cold
      sensitivity or can inhibit cold-sensitive neurons and diminish cooling-mediated
      pain relief (analgesia). Nonetheless, cold pain (allodynia) is prevalent in many
      inflammatory and neuropathic pain settings, with little known of the mechanisms
      promoting pain vs. those dampening analgesia. Here, we show that cold allodynia
      induced by inflammation, nerve injury, and chemotherapeutics is abolished in mice
      lacking the neurotrophic factor receptor glial cell line-derived neurotrophic
      factor family of receptors-alpha3 (GFRalpha3). Furthermore, established cold
      allodynia is blocked in animals treated with neutralizing antibodies against the
      GFRalpha3 ligand, artemin. In contrast, heat and mechanical pain are unchanged,
      and results show that, in striking contrast to the redundant mechanisms
      sensitizing other modalities after an insult, cold allodynia is mediated
      exclusively by a single molecular pathway, suggesting that artemin-GFRalpha3
      signaling can be targeted to selectively treat cold pain. 

PMID- 27051071
TI  - A Cross-Sectional Comparison of Quality of Life Between Physically Active and
      Underactive Older Men With Prostate Cancer.
AB  - Men with prostate cancer experience many side effects and symptoms that may be
      improved by a physically active lifestyle. It was hypothesized that older men
      with prostate cancer who were physically active would report significantly higher
      levels of quality of life (QOL) as assessed by the WHOQOL-BREF and the WHOQOL
      OLD. Of the 348 prostate cancer survivors who were invited to participate in the
      present postal survey, 137 men returned the questionnaires. Those who were
      physically active had significantly lower prostate specific antigen (PSA) scores
      and higher social participation than those insufficiently active. These findings
      offer some support for the benefits of physical activity (PA) within the prostate
      cancer population in managing the adverse side effects of their treatments on
      aspects of their QOL. Future research should more closely examine what types of
      PA best promote improvements in varying aspects of QOL and psychological well
      being for prostate cancer survivors.

PMID- 27051072
TI  - Nordic Walking Improves Postural Alignment and Leads to a More Normal Gait
      Pattern Following Weeks of Training: A Pilot Study.
AB  - The aim of this study was to investigate the impact of an 8-week Nordic walking
      (NW) intervention on older adult gait patterns and postural alignment. Twelve
      healthy older adults aged 60-80 years (8 female, 4 male) participated, all
      performing two 6-min walk tests (one with poles [WP], one without poles [NP]) and
      six 5-m walk trials (3 WP, 3 NP) at pre- and posttesting. Gait and postural
      variables were compared between poling conditions (i.e., WP to NP) as well as
      before and following the intervention. Following training, pole use resulted in
      various gait changes including: longer stride, faster gait, and increased power
      generation at the hip (H3) and power absorption at the knee (K1 and K4). We
      conclude that an initial 8-week training period is necessary for novice NW to
      perfect technique and to restore gait to a more natural, normal pattern following
      training.

PMID- 27051073
TI  - Fatigue Alters the Pattern of Physical Activity Behavior in Older Adults:
      Observational Analysis of Data from the Generation 100 Study.
AB  - Fatigue has been associated with reductions in daily activity of older people.
      Summary measures of daily physical activity provide limited understanding of how
      fatigue affects physical activity behavior. This study examined the hour-by-hour
      energy expenditure estimated from accelerometry data to provide insight into
      physical activity behaviors of older people experiencing fatigue. Fatigued
      participants were matched to 'not fatigued' participants by age, sex, and BMI.
      Each group consisted of 86 people with a mean age 73.8 years (SD 2.0), BMI 26.5
      kg?m-2 (SD 3.9) and 61% female. The phase-space plot, constructed to express rate
      of change of average vertical axis counts per hour as a time series, showed
      fatigued participants deviated from the not fatigued participants during the
      morning period, when hour-by-hour activity was increasing. Older people who feel
      fatigued have a different morning activity pattern, which appears to lead to the
      lower overall levels of physical activity.

PMID- 27051074
TI  - Socioeconomic Status and Life-Space Mobility in Old Age.
AB  - Life-space mobility describes the extent of community mobility of older persons.
      The aim of this cross-sectional study was to examine the relationship between
      socioeconomic status (SES) and life-space mobility and to investigate whether
      associations might be explained by SES-related disparities in health and
      functioning. The participants (n = 848) were community-dwelling adults aged 75
      90. Education and occupation were used to indicate SES. Life-space assessment
      (range 0-120) was used to indicate distance and frequency of moving and
      assistance needed in moving. People with low education had lower life-space
      mobility scores than those with intermediate or high education: marginal means
      63.5, 64.8, and 70.0 (p = .003), respectively. SES-related health disparities,
      i.e., higher body mass index, poorer cognitive capacity, and poorer physical
      performance explained the association, rendering it nonsignificant (marginal
      means 65.2, 65.3, and 67.5, p = .390). Low SES and restricted life-space mobility
      often coexist with overweight, reduced cognition, and poorer physical
      performance.

PMID- 27051075
TI  - Prognostic Value of Perineural Invasion in Esophageal and Esophagogastric
      Junction Carcinoma: A Meta-Analysis.
AB  - OBJECTIVE: Here we aimed to clarify the prognostic significance of perineural
      invasion (PNI) in esophageal and esophagogastric junction (EGJ) carcinoma.
      METHODS: A comprehensive literature search for relevant reports published up to
      July 2015 was performed using Pubmed and Embase databases. The pooled HR and 95%
      CI for overall survival (OS) and disease-free survival (DFS) were used to assess
      the prognostic value. The association of PNI with pathological characteristics
      was evaluated by OR and 95% CI. RESULTS: A total of 13 cohorts were retrieved,
      covering 2770 patients treated by surgery. The cumulative analysis revealed a
      statistical correlation between PNI and poor OS (HR = 1.76, 95% CI: 1.54-2.20,
      and P < 0.00001), as well as poor DFS (HR = 1.96, 95% CI: 1.42-2.71, and P <
      0.001). Moreover, analysis of 1475 patients showed improved PNI in T3 + T4 (OR =
      0.39, 95% CI: 0.21-0.70, and P = 0.002), N+ (OR = 0.52, 95% CI: 0.40-0.69, and P
      < 0.00001), and G3 + G4 (OR = 0.66, 95% CI: 0.48-0.90, and P = 0.008) patients
      compared with T1 + T2, N-, and G1 + G2 ones, respectively. No significant
      heterogeneity was found between the studies. CONCLUSIONS: PNI is an adverse
      prognostic biomarker in esophageal and EGJ carcinoma. Moreover, PNI implies
      advanced T, N stage and poor cell differentiation.

PMID- 27051076
TI  - Dream Recall Frequencies and Dream Content in Wilson's Disease with and without
      REM Sleep Behaviour Disorder: A Neurooneirologic Study.
AB  - Objective. Violent dream content and its acting out during rapid eye movement
      sleep are considered distinctive for rapid eye movement sleep behaviour disorder
      (RBD). This study reports first quantitative data on dreaming in a cohort of
      patients with treated Wilson's disease (WD) and in patients with WD with RBD.
      Methods. Retrospective questionnaires on different dimensions of dreaming and a
      prospective two-week home dream diary with self-rating of emotions and blinded,
      categorical rating of content by an external judge. Results. WD patients showed a
      significantly lower dream word count and very few other differences in dream
      characteristics compared to age- and sex-matched healthy controls. Compared to WD
      patients without RBD, patients with WD and RBD reported significantly higher
      nightmare frequencies and more dreams with violent or aggressive content
      retrospectively; their prospectively collected dream reports contained
      significantly more negative emotions and aggression. Conclusions. The reduction
      in dream length might reflect specific cognitive deficits in WD. The lack of
      differences regarding dream content might be explained by the established
      successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance
      with the current definition of RBD, violent, aggressive dream content seems to be
      a characteristic of RBD also in WD. 

PMID- 27051077
TI  - Effect of Preoperative Inflammatory Status and Comorbidities on Pain Resolution
      and Persistent Postsurgical Pain after Inguinal Hernia Repair.
AB  - Poor acute pain control and inflammation are important risk factors for
      Persistent Postsurgical Pain (PPSP). The aim of the study is to investigate, in
      the context of a prospective cohort of patients undergoing hernia repair,
      potential risk factors for PPSP. Data about BMI, anxious-depressive disorders,
      neutrophil-tolymphocyte ratio (NLR), proinflammatory medical comorbidities were
      collected. An analysis for correlation between comorbidities and PPSP was
      performed in those patients experiencing chronic pain at 3 months after surgery.
      Tramadol resulted less effective in pain at movement in patients with a
      proinflammatory status. Preoperative hypertension and NLR > 4 were correlated
      with PPSP intensity. Regional anesthesia was significantly protective on PPSP
      when associated with ketorolac. Patients with pain at 1 month were significantly
      more prone to develop PPSP at 3 months. NSAIDs or weak opioids are equally
      effective on acute pain and on PPSP development after IHR, but Ketorolac has
      better profile in patients with inflammatory background or undergoing regional
      anesthesia. Drug choice should be based on their potential side effects,
      patient's profile (comorbidities, preoperative inflammation, and hypertension),
      and type of anesthesia. Close monitoring is necessary to early detect pain
      conditions more prone to progress to a chronic syndrome. 

PMID- 27051078
TI  - Linking CD11b (+) Dendritic Cells and Natural Killer T Cells to Plaque
      Inflammation in Atherosclerosis.
AB  - Atherosclerosis remains the leading cause of death and disability in our Western
      society. To investigate whether the dynamics of leukocyte (sub)populations could
      be predictive for plaque inflammation during atherosclerosis, we analyzed innate
      and adaptive immune cell distributions in blood, plaques, and lymphoid tissue
      reservoirs in apolipoprotein E-deficient (ApoE(-/-)) mice and in blood and
      plaques from patients undergoing endarterectomy. Firstly, there was predominance
      of the CD11b(+) conventional dendritic cell (cDC) subset in the plaque. Secondly,
      a strong inverse correlation was observed between CD11b(+) cDC or natural killer
      T (NKT) cells in blood and markers of inflammation in the plaque (including CD3,
      T-bet, CCR5, and CCR7). This indicates that circulating CD11b(+) cDC and NKT
      cells show great potential to reflect the inflammatory status in the
      atherosclerotic plaque. Our results suggest that distinct changes in inflammatory
      cell dynamics may carry biomarker potential reflecting atherosclerotic lesion
      progression. This not only is crucial for a better understanding of the
      immunopathogenesis but also bares therapeutic potential, since immune cell-based
      therapies are emerging as a promising novel strategy in the battle against
      atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in
      atherosclerosis serves as a good candidate for future investigations. 

PMID- 27051080
TI  - Public Health Challenges in India: Seizing the Opportunities.

PMID- 27051079
TI  - Thyroid Hormones, Oxidative Stress, and Inflammation.
AB  - Inflammation and oxidative stress (OS) are closely related processes, as well
      exemplified in obesity and cardiovascular diseases. OS is also related to
      hormonal derangement in a reciprocal way. Among the various hormonal influences
      that operate on the antioxidant balance, thyroid hormones play particularly
      important roles, since both hyperthyroidism and hypothyroidism have been shown to
      be associated with OS in animals and humans. In this context, the nonthyroidal
      illness syndrome (NTIS) that typically manifests as reduced conversion of
      thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic
      conditions is still a debated topic. The pathophysiological mechanisms of this
      syndrome are reviewed, together with the roles of deiodinases, the enzymes
      responsible for the conversion of T4 to T3, in both physiological and
      pathological situations. The presence of OS indexes in NTIS supports the
      hypothesis that it represents a condition of hypothyroidism at the tissue level
      and not only an adaptive mechanism to diseases. 

PMID- 27051081
TI  - Controversies Continue: Universal Supplementation of Megadose of Vitamin A to
      Young Children in India.
AB  - The universal megadose of vitamin A (MDVA) supplementation program was started in
      the year 1970. The program is presently in continuation for the prevention of
      nutritional blindness and possibly reduction in under-five mortality rate (U5MR).
      Presently, blindness due to vitamin A deficiency (VAD) has disappeared and the
      difference between U5MR and infant mortality rate (IMR) is less than 10 thus MDVA
      is unlikely to have any impact on mortality. The continuation of universal MDVA
      needs to be modified based on the current scientific evidence. 

PMID- 27051082
TI  - Application of Mixed Method Approach in Public Health Research.

PMID- 27051083
TI  - Quality Assurance for Accuracy of Anthropometric Measurements in Clinical and
      Epidemiological Studies: [Errare humanum est = to err is human].
AB  - Anthropometry involves the external measurement of morphologic traits of human
      beings. High quality anthropometric measurements are fundamental to clinical and
      epidemiological research. The measurements for each method have inherent
      variations, either due to biologic variation or due to error in measurement.
      Errors in measurement cannot be avoided completely but they can be minimized to a
      large extent. We define methods to estimate measurement error in anthropometry,
      offer guidelines for acceptable error, and suggest ways to minimize measurement
      error; thereby improving anthropometry quality in health assessments. We propose
      that special attention be paid to the following six key parameters for quality
      assurance of anthropometric measurements: (i) Identification of certified lead
      anthropometrist and trainer, (ii) manual of standard operating procedures, (iii)
      choice of robust equipment, (iv) equipment calibration, (v) standardization
      training and certification, and (vi) measurements resampling. 

PMID- 27051084
TI  - Burden of Ocular Motility Disorders at a Tertiary Care Institution: A Case to
      Enhance Secondary Level Eye Care.
AB  - AIM: To evaluate the profile of strabismus and amblyopia in patients presenting
      to a tertiary care institution in order to understand the disease burden.
      MATERIALS AND METHODS: A retrospective, prospective hospital-based observational
      study was conducted at a tertiary level eye care hospital in India. All patients
      with strabismus or amblyopia who presented over a 1-year period were identified
      and referred to the squint clinic, where they were evaluated with a detailed
      clinical history and examination. RESULTS: A total of 24475 patients were
      evaluated, of which 1950 had strabismus or amblyopia. The overall magnitude of
      amblyopia and strabismus was 2.0% [95% confidence interval (CI), 1.8-2.2)] and
      6.9% (95% CI, 6.6-7.2), respectively. About 20% of those seeking an ophthalmic
      consultation were children and they constituted over half of the population
      referred to the squint clinic. Among younger children, the burden of amblyopia
      and strabismus was 84.4% and 26.6%, respectively. Among the referred patients,
      strabismus was noted in 84.6% (N = 1649), most of the cases of which was of the
      comitant subtype (78.1%, N = 1288) with an equal distribution of exotropia and
      esotropia. Paralytic [12.9% (N = 251)] and restrictive [4.7% (N = 85)] squint
      constituted the remaining burden of strabismus. CONCLUSION: Strabismus and
      amblyopia affect a sizeable proportion of patients presenting to a tertiary care
      ophthalmology setup. A significantly higher burden is present in the pediatric
      population. The majority of the cases of strabismus are of a comitant variety,
      which do not merit tertiary level eye care. There is a need to improve pediatric
      eye care at a secondary level to reduce the immense burden on tertiary referral
      centers.

PMID- 27051085
TI  - Taken to Health Care Provider or Not, Under-Five Children Die of Preventable
      Causes: Findings from Cross-Sectional Survey and Social Autopsy in Rural India.
AB  - BACKGROUND: Under-five children in India continue to die from causes that can
      either be treated or prevented. The data regarding causes of death, community
      care-seeking practices, and events prior to death are needed to guide and refine
      health policies for achieving national goals and targets. MATERIALS AND METHODS:
      A cross-sectional survey covering rural areas of 16 districts from eight states
      across India was conducted to understand the causes of deaths and the health
      seeking patterns of caregivers prior to the death of such children. Mothers of
      the deceased children were interviewed. The physician review process was used to
      assign cause of death. The qualitative data were analyzed as per standard
      methods, while STATA version 10 was used for analysis of quantitative data.
      FINDINGS: A total of 1,488 death histories were captured through verbal autopsy.
      Neonatal etiologies, acute respiratory infection (ARI), and diarrhea accounted
      for approximately 63.1% of all deaths in the under-five age group. The causes of
      death in neonates showed that birth asphyxia, prematurity, and neonatal
      infections contributed to more than 67.5% of all neonatal deaths, while in
      children aged 29 days to 59 months, ARI and diarrhea accounted for 54.3% of
      deaths. Care providers of 52.6% of the neonates and 21.7% of infants and under
      five children did not seek any medical care before the death of the child.
      Substantial delays in seeking care occurred at home and during transit. For those
      who received medical care, there was an apparent amongst in their caregivers
      toward private health providers. CONCLUSION: The deaths of neonates and
      postneonates taken to any health facilities highlight the need for providing
      equitable and high-quality health services in India. The findings could be used
      for policy planning and program refinement in India.

PMID- 27051086
TI  - Risk Factors for DOTS Treatment Default Among New HIV-TB Coinfected Patients in
      Nalgonda (Dist.) Telangana (State): A Case Control Study.
AB  - BACKGROUND: The therapeutic regimens as recommended by the Revised National TB
      Control Programme (RNTCP) have been shown to be highly effective for both
      preventing and treating tuberculosis, but poor adherence to medication is a major
      barrier to its global control. AIM AND OBJECTIVES: The study was conducted to
      assess the influence of patient related factors for DOTS Treatment Default among
      HIV-TB Co-infected cases. SETTING AND DESIGN: This was a case control study
      conducted in Nalgond, Telangana. MATERIALS AND METHODS: All new HIV-TB coinfected
      and DOTS-defaulted patients registered under RNTCP for the period from January
      2010 to December 2012 were selected. Of the 154 patients, 23 had died and 11
      could not be traced, and these were excluded. Thus the total number of available
      cases were 120 for those age- and sex-matched controls (HIV-TB coinfected
      patients and those who had completed the DOTS regimen successfully) were
      selected. RESULTS: The mean age was 36.5 +/- 9 years; the majority (23.3%) of
      patients defaulted during the second month of treatment. Significant risk factors
      associated with defaulting included unskilled occupation [adjusted odds ratio
      (AOR: 3.56; 95% confidence interval (CI): 1.1-11.56], lower middle class
      socioeconomic status (AOR: 17.16; 95% CI: 3.93-74.82), small family size (AOR:
      21.3; 95% CI: 6.4-70.91), marital disharmony (AOR: 6.78; 95% CI: 1.93-23.76), not
      being satisfied with the conduct of health personnel (AOR: 7.38; 95% CI: 2.32
      23.39), smoking (AOR: 8.5; 95% CI: 2.31-31.21), and side effects of drugs (AOR:
      4.18; 95% CI: 1.35-12.9). CONCLUSION: Unskilled occupation, marital disharmony,
      small family size, lower middle class socioeconomic status, not being satisfied
      with the conduct of health personnel, smoking, and drug side effects were
      significantly associated with defaulting. Information on the pattern of
      tuberculosis (TB), the outcome of anti-tuberculosis treatment (ATT), and the
      factors associated with it will help in planning interventions to improve
      adherence to DOTS treatment.

PMID- 27051087
TI  - Does Awareness of Status and Risks of Human Immunodeficiency Virus Impact Risky
      Transmission Behavior Among Infected Adolescents? A Case Study of Clients
      Attending an Antiretroviral Therapy (ART) Clinic in Kano, Kano State, Nigeria.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-positive adolescents by virtue of
      their position are prone to dangerous behaviors including risk-taking for HIV
      transmission. OBJECTIVE: To determine the awareness of HIV status and risk
      factors for HIV transmission among HIV-positive adolescents, and how these impact
      their behavior. MATERIALS AND METHODS: A case study approach was used to study a
      random sample of 400 HIV-positive adolescent children attending an antiretroviral
      (ART) clinic in Kano, Kano State, Nigeria. Data were analyzed using Statistical
      Package for the Social Sciences (SPSS) 16.0 computer statistical software.
      RESULT: The mean age of the adolescents was 14.9 +/- 3.15 years. The majority
      were females (54.8%) from a polygamous family (57.5%). About two-thirds or 251
      (62.8%) patients knew their HIV status. The age of 14 years and above (z = 11.36,
      P = 0.0001) and having at least secondary school level of education (z = 2.78, P
      = 0.005) were significantly associated with awareness of HIV status on binary
      logistic regression. Up to 311 (77.8%) patients had good awareness of the risks
      of HIV transmission. Awareness of risk of HIV transmission was associated with
      awareness of HIV status (X(2) = 166.2, P = 0.0001). There was a significant
      variation in the behaviors between those who were aware of their HIV status and
      those who were not. Paradoxically, the percentage differences in risk-taking were
      remarkably high in all the variables examined, and were all in the direction of
      the adolescents who had good knowledge of the risk factors for HIV transmission.
      CONCLUSION AND RECOMMENDATION: Health ministries, development partners working in
      this field, and behavioral change communication experts should develop formidable
      strategies for addressing this menace. There is also a dire need for further
      research in this area.

PMID- 27051088
TI  - Problem-Based Learning as an Effective Learning Tool in Community Medicine:
      Initiative in a Private Medical College of a Developing Country.
AB  - BACKGROUND: Knowledge of community medicine is essential for health care
      professionals to function as efficient primary health care physicians. Medical
      students learning Community Medicine as a subject are expected to be competent in
      critical thinking and generic skills so as to analyze community health problems
      better. However, current teaching by didactic lectures fails to develop these
      essential skills. Problem-based learning (PBL) could be an effective strategy in
      this respect. This study was hence done to compare the academic performance of
      students who were taught Community Medicine by the PBL method with that of
      students taught by traditional methods, to assess the generic skills of students
      taught in a PBL environment and to assess the perception of students toward PBL
      methodology. MATERIALS AND METHODS: This study was conducted among seventh
      semester final-year medical students between June and November 2014. PBL was
      introduced to a randomly chosen group of students, and their performance in an
      assessment exam at the end of postings was compared with that of the remaining
      students. Generic skills and perception toward PBL were also assessed using
      standardized questionnaires. RESULTS: A total of 77 students took part in the
      brainstorming session of PBL. The correlation between self-assigned scores of the
      participants and those assigned by the tutor in the brainstorming session of PBL
      was significant (r = 0.266, P = 0.05). Out of 54 students who took part in the
      presentation session, almost all 53 (98.1%) had good perception toward PBL.
      Demotivational scores were found to be significantly higher among males (P =
      0.024). The academic performance of students (P < 0.001) and success rates (P =
      0.05) in the examination were higher among students who took part in PBL compared
      to controls. CONCLUSION: PBL helped improve knowledge of students in comparison
      to those exposed only to didactic lectures. As PBL enabled students to identify
      the gaps in their knowledge and enhanced their group functioning and generic
      skills, we recommend PBL sessions: They would help optimize the training in
      Community Medicine at medical schools. Good correlation of tutor and self
      assessment scores of participants in the brainstorming session suggests that the
      role of tutors could be restricted to assessment in presentation sessions alone.
      Demotivation, which hinders group performance in PBL, needs to be corrected by
      counselling and timely feedback by the tutors.

PMID- 27051089
TI  - Impact Evaluation of Domains of Learning on Universal Work Precautions (UWP)
      Amongst Nursing Staff in a Tertiary Care Hospital, Western India.
AB  - INTRODUCTION: Second key strategy of National AIDS Control Program (NACP IV) is
      comprehensive care and support by providing quality services through zero stigma
      and discrimination. Quality of services can be improved by eliminating stigma and
      discrimination and making health care provider aware of associated occupational
      hazards. Nursing staff play crucial role and are more at risk therefore their
      understanding, perception and skill must be assessed in different domains of
      learning to improve the contents and methodology of trainings. MATERIAL AND
      METHODS: Total 85 nursing staff underwent 1 day training in 3 batches focusing on
      Universal Work Precautions (UWP), Post Exposure Prophylaxis (PEP) and
      sensitization of the participants towards PLHA (People living with HIV/AIDS).
      Their learning was evaluated under different domains (cognitive, psychomotor and
      affective) using structured questionnaire. RESULTS: In pretest evaluation scores
      showed minor and statistically not significant variations in terms of
      participant's gender, age, designation work experience and status of having
      received any similar training in the past. Impact of the training was visible as
      overall mean scores increased from 10.6 +/- 2.7 to 13.8 +/- 5.8; gain being
      statistically highly significant (P value < 0.001). Gain was highest in cognitive
      (from 58% to 77%) followed by psychomotor (from 48% to 62%) and minimal in
      affective domain (from 75% to 76%). CONCLUSIONS: After undergoing the training,
      participants were benefitted more in cognitive domain than psychomotor and
      affective domain. Acquired knowledge, skill and communication skill if evaluated
      as done in this study will improve the methodology of such trainings making them
      more effective.

PMID- 27051090
TI  - Assessment of Self-Reported Emotional and Behavioral Difficulties Among Pre
      University College Students in Bangalore, India.
AB  - BACKGROUND: The understanding of youth mental health needs and development of
      service delivery models is a national public health challenge. OBJECTIVES: The
      rates and predictors of emotional and behavioral problems among 1087 youth were
      assessed in a pre-university college in Bangalore, India. Variations in rates of
      disturbance, identified by using different cut-off points, were also examined.
      MATERIALS AND METHODS: The Strengths and Difficulties Questionnaire was used as a
      self-report screening tool. RESULTS: Results indicated that 10.1% of adolescents
      had total difficulty levels in the abnormal range, with 9% at risk for emotional
      symptoms, 13% for conduct problems, 12.6% for hyperactivity/inattention and 9.4%
      for peer problems. Select gender differences were present. Cut-off scores derived
      from the sample yielded lower estimates of disturbance than the published cut
      offs. Regression analysis identified predictors of total difficulty levels.
      CONCLUSIONS: Implications for assessment of youth mental health and planning
      targeted services in educational institutions are discussed.

PMID- 27051091
TI  - Caffeine Intake Among Adolescents in Delhi.
AB  - BACKGROUND: Availability and advertising of caffeinated drinks is on the rise in
      Indian market. Excess caffeine intake may have deleterious effects on health.
      OBJECTIVE: To estimate the daily consumption of caffeine among urban school-going
      adolescents from Delhi. MATERIALS AND METHODS: A school-based survey was
      conducted to determine the amount and pattern of caffeine consumption among
      students of classes 9-12, using a self-administered questionnaire. RESULTS: Of
      300 participants (median age 15 year, 174 boys), 291 (97%) were consuming
      caffeine [mean (SD): 121.0 (98.2) mg/day]. Nineteen (6%) students were consuming
      more than 300 mg of caffeine per day. Tea/coffee contributed to more than 50% of
      the caffeine intake. The rest was derived from cola beverages, chocolates, and
      energy drinks. CONCLUSION: Average caffeine consumption among school-going
      adolescents from Delhi is high. The findings of this preliminary survey need to
      be confirmed in larger data sets.

PMID- 27051092
TI  - An Epidemiological Study of Overweight and Obesity Among Women in an Urban Area
      of North India.
AB  - BACKGROUND: Obesity is a complex, multi-factorial chronic disease. Overweight and
      obesity are the fifth leading risk for global deaths. OBJECTIVES: To find the
      prevalence and risk factors for obesity in women aged 20-60 years in Ludhiana
      city. METHODS: The present study is a community based cross sectional study
      carried out in an urban area of Ludhiana among women aged 20-60 years. Among the
      study population of 324 women, a pre-designed and pre-tested questionnaire was
      used to record the socio-demographic and anthropometric profile of women. Chi
      square test and logistic regression was used to find the association of obesity
      and hypertension with socio-demographic variables. RESULTS: The prevalence of
      overweight and obesity was 12.7% and 29.6% respectively. Obesity was found to be
      more common among middle-aged Punjabi housewives belonging to upper socio
      economic strata. There was strong association between overweight/obesity and
      hypertension.

PMID- 27051093
TI  - Effectiveness and Feasibility of Weekly Iron and Folic Acid Supplementation to
      Adolescent Girls and Boys through Peer Educators at Community Level in the Tribal
      Area of Gujarat.
AB  - BACKGROUND: Anemia during adolescence affects growth and development of girls and
      boys increasing their vulnerability to dropping out-of-school. Hence investing in
      preventing anemia during adolescence is critical for their survival, growth and
      development. OBJECTIVE: To find out the burden of anemia on adolescent age group
      in the tribal area of Jhagadia block and to assess the change in the hemoglobin
      level through the weekly Iron and Folic Acid IFA (DOTS) directly observed
      treatment supplementation under Supervision by Peer Educators at Community level
      among adolescents. METHODS: Community based intervention study conducted with
      adolescents (117 girls and 127 boys) aged 10-19 years, through supplementation of
      IFA (DOTS) by trained Peer Educators for 52 weeks in 5 tribal villages of
      Jhagadia. Hemoglobin level was determined by HemoCue method before and after
      intervention and sickle cell anemia by Electrophoresis method. Primary data on
      hemoglobin and number of tablets consumed was collected and statistically
      analyzed in SPSS 16.0 software by applying paired t-test. RESULTS: The overall
      findings suggest that the prevalence of anemia reduced from 79.5% to 58% among
      adolescent girls and from 64% to 39% among boys. Mean rise of hemoglobin seen was
      1.5 g/dl among adolescent boys and 1.3 g/dl among girls. A significant
      association was found in change in hemoglobin before and after intervention (P =
      0.000). CONCLUSION: Prevalence of anemia among girls and boys can be reduced in
      their adolescent phase of life, through weekly supplementation of iron folic acid
      tablets under direct supervision and Nutrition Education by Peer Educator at
      community level.

PMID- 27051094
TI  - Empowering the Community to Manage Diabetes Better: An Integrated Partnership
      Based Model.
AB  - CONTEXT: Rising number of diabetes cases in India calls for collaboration between
      the public and private sectors. AIMS: Municipal Corporation of Greater Mumbai
      (MCGM) partnered with Eli Lilly and Company (India) [Eli Lilly] to strengthen the
      capacity of their diabetes clinics. MATERIALS AND METHODS: Medical Officers,
      dispensaries and Assistant Medical Officers (AMOs) located at attached health
      posts were trained on an educational tool, Diabetes Conversation MapTM (DCM) by a
      Master Trainer. This tool was then used to educate patients and caregivers
      visiting the MCGM diabetes clinics. RESULTS: Twenty-eight centers conducted 168
      sessions, and 1616 beneficiaries availed the education over six months. General
      feedback from health providers was that DCM helps clear misconceptions among
      patients and caregivers in an interactive way and also improves compliance of
      patients. CONCLUSIONS: This communication highlights a unique public-private
      partnership where the sincere efforts of public sector organization (MCGM) were
      complemented by the educational expertise lent by a private firm.

PMID- 27051095
TI  - Why India Needs Crashworthy Vehicles.

PMID- 27051096
TI  - Assessment of the mind in chronic obstructive pulmonary disease: Mind or never
      mind.

PMID- 27051097
TI  - Endoscopic ultrasound in mediastinal tuberculosis.
AB  - BACKGROUND: Tubercular lymphadenitis is the commonest extra pulmonary
      manifestation in cervical and mediastinal locations. Normal characteristics of
      lymph nodes (LN) have been described on ultrasonography as well as by Endoscopic
      Ultrasound. Many ultrasonic features have been described for evaluation of
      mediastinal lymph nodes. The inter and intraobserver agreement of the
      endosonographic features have not been uniformly established. METHODS AND
      RESULTS: A total of 266 patients underwent endoscopic ultrasound guided fine
      needle aspiration and 134 cases were diagnosed as mediastinal tuberculosis. The
      endoscopic ultrasound location and features of these lymph nodes are described.
      CONCLUSION: Our series demonstrates the utility of endoscopic ultrasound guided
      fine needle aspiration as the investigation of choice for diagnosis of
      mediastinal tuberculosis and also describes various endoscopic ultrasound
      features of such nodes.

PMID- 27051098
TI  - Tuberculosis associated pulmonary hypertension: The revelation of a clinical
      observation.
AB  - BACKGROUND: Pulmonary tuberculosis is not listed as a cause of pulmonary
      hypertension (PH). Scanty information is available in the literature regarding
      this issue. METHODS: A group of patients with a history of pulmonary tuberculosis
      were diagnosed to have PH on the basis of a novel clinico-radio-echocardiographic
      criteria. Subdivided into two groups on the basis of the history of smoking, we
      looked for their demographic, spirometric, radiological characteristics along
      with the quality of life assessment. RESULTS: A total of 40 patients (21 smokers
      and 19 nonsmokers) were found to have PH with history of pulmonary tuberculosis.
      The two groups were similar radiologically including the extent of fibrosis. The
      nonsmoker group had lower age range (52.16 +/- 14.81 vs. 63.1 +/- 10.05, P =
      0.01), worse chronic obstructive pulmonary disease (COPD) assessment test score
      (16.11 +/- 6.24 vs. 13.9 +/- 5.6, P = 0.25) and higher pulmonary artery (PA)
      pressure (46.39 +/- 7.44 vs. 44.55 +/- 8.04, P = 0.46) compared to the smokers.
      Overall and for the smoker group, in particular, the spirometric pictures were
      favoring obstruction without reversibility as in COPD (forced expiratory volume
      in 1 second [FEV1] % as 64.26 +/- 18.38 and 58.85 +/- 14.61 with % of predicted
      FEV1 being 43.74 +/- 17.26 and 42.38 +/- 16.64 respectively). However, those with
      no history of smoking had restrictive changes as in diffuse parenchymal lung
      disease (DPLD) in their spirometry (FEV1/forced vital capacity [FVC] of 79.33 +/-
      19.93 and FVC as 49.67 +/- 11.54% of predicted). The smoker group had far more
      obvious involvement of the small airways in terms of change in FEF25-75 compared
      to nonsmokers (FEF25-75 = 22.85 +/- 19.68 vs. 63.83 +/- 48.61). CONCLUSION: PH
      appears associated with the history of pulmonary tuberculosis. With or without a
      history of smoking, they pose two distinct phenotypes in spirometry as COPD and
      DPLD. The DPLD phenotype had worse quality of life.

PMID- 27051099
TI  - Demographic characteristic and analysis of pulmonary paragonimiasis in patients
      attending RIMS, Manipur.
AB  - BACKGROUND: Human infection by the lung fluke Paragonimus westermani is widely
      distributed in Africa, Asia, and South America. Transmission of the parasite to
      humans primarily occurs through the consumption of raw or undercooked crabs.
      Clinical features of recently diagnosed pulmonary Paragonimiasis show that
      patients present with a variety of clinical and radiological findings, frequently
      mimics tuberculosis and lung cancer. METHODS: Here in this study, we report a
      cross-sectional study of pulmonary paragonimiasis in our institute over a period
      of two year. RESULTS: it was observed that out of eleven cases, prevalence of
      paragonimiasis was almost equal among both the genders, with a mean age of 38.1
      +/- 16.96, affecting people from hills. Three patients were erroneously treated
      with antitubercular drugs without any relief. The association with eosinophilia
      in the peripheral blood and tissue[16] was seen in all the study subjects and
      majority patients had pleural fluid eosinophilia. Patients were diagnosed by
      serological test, Paragonimus ova in Sputum smear and Pleural fluid. All study
      subjects had excellent clinical responses to praziquantel given at dose of 25
      mg/kg given orally 3 times daily for 3 consecutive days. CONCLUSIONS: There is a
      need to generate awareness among the clinicians and public regarding
      Paragonimiasis and to consider it in differential diagnosis of TB and carcinoma
      lung. Physicians should consider the possibility of paragonimiasis among patients
      who present with chest complaints with eosinophilia from the endemic regions.

PMID- 27051100
TI  - Pulmonary involvement in systemic sclerosis: A clinical profile.
AB  - BACKGROUND: Systemic sclerosis is a generalized disorder of connective tissue
      affecting skin and internal organs. Lung involvement accounts for significant
      morbidity and is a leading cause of mortality in patients. OBJECTIVES: This study
      intends to study the frequency of occurrence of pulmonary involvement in
      progressive systemic sclerosis (PSS) and to describe the clinical and
      radiological picture of pulmonary involvement in PSS. MATERIALS AND METHODS: This
      was a descriptive cross-sectional study. A detailed history, modified Rodnan
      score, clinical examination, routine investigation, antinuclear antibody, immuno
      biot, chest X-ray (CXR), pulmonary function test (PFT), and 6 min walk test
      (6MWT) were performed on all patients. High resolution computed tomography was
      done on those who consented. RESULTS: Hundred subjects with PSS were included in
      the study; 90 were females and 10 were males. Common presenting complaints were
      skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits
      beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in
      92%. Chest wall thickening was seen in 40 subjects (40%). 90 (90%) of the studied
      subjects had pulmonary involvement, longer duration of disease was significantly
      associated with pulmonary involvement (P < 0.05). Dyspnea, cough, bilateral
      crepitations, CXR, Borg score, and Rodnan score was found to be significantly
      associated with severe pulmonary involvement (P < 0.05). CONCLUSION: The
      prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3(rd)
      of patients, that is 29 (29%) were detected to have pulmonary involvement despite
      being asymptomatic for respiratory complaints, hence early screening and
      evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and
      easily available screening tests which can be used in resource-limited settings.

PMID- 27051101
TI  - Health-related quality of life of chronic obstructive pulmonary disease patients:
      Results from a community based cross-sectional study in Aligarh, Uttar Pradesh,
      India.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      airflow limitation that is not fully reversible. It is an incurable disease with
      improvement in quality of life (QOL) as a major focus area for management. This
      study assesses the QOL of COPD patients and the factors affecting it. MATERIALS
      AND METHODS: All 124 patients diagnosed with COPD in a larger cross-sectional
      study to determine the prevalence of COPD were assessed for their QOL using St.
      George's respiratory questionnaire for COPD patients (SGRQ-C). Spirometry was
      performed to assess lung function and diagnose COPD. Chronic lung disease (CLD)
      severity index was used to assess the severity of symptoms and the Medical
      Research Council questionnaire was used to assess the severity of dyspnea.
      Sociodemographic data regarding the patients were also recorded. RESULTS:
      Patients with COPD showed significantly reduced health-related quality of life
      (HRQOL). CLD estimate for severity of lung disease and the Medical Research
      Council assessment for dyspnea and the duration of illness showed a highly
      significant positive correlation with HRQOL. There was a statistically
      significant negative correlation between lung function and SGRQ-C score.
      Increasing age, increased quantum of smoking, and lower socioeconomic status were
      correlated with poorer HRQOL. No association between QOL and education, body mass
      index (BMI), and gender was observed. CONCLUSION: This study showed that Indian
      patients with COPD had reduced HRQOL. Poor lung function, increased disease
      duration and smoking, and worsening symptoms impacted HRQOL negatively.

PMID- 27051102
TI  - Pharmacoeconomic benefit of cisplatin and etoposide chemoregimen for metastatic
      non small cell lung cancer: An Indian study.
AB  - BACKGROUND: The incidence of lung cancer is rising in developing countries like
      India. Due to unaffordability among the low socioeconomic status (SES) patients,
      there is a significant delay in seeking appropriate medical treatment due to
      which a high proportion of patients present in an advanced/metastatic stage and
      the outcomes are poor. OBJECTIVE: In this study, we studied the progression-free
      survival (PFS) and the pharmacoeconomic benefits with the cisplatin plus
      etoposide (EtoP) chemo regimen and compared it with the current generation chemo
      regimen. MATERIALS AND METHODS: We performed a retrospective analysis of
      metastatic nonsmall cell lung cancer patients who received one or more cycles of
      platinum-based chemotherapy between 2011 and 2014. RESULTS: Of the 304 patients,
      56.6% of the patients were of the low SES. Of the low socioeconomic group
      patients, 67.45% and 31.4% received etoposide and paclitaxel platinum doublet
      combination regimen as first line, respectively. The mean PFS with the etoposide,
      paclitaxel, pemetrexed, and gemcitabine platinum-based doublet regimens were
      9.35, 10, 10.76, and 9.83 months, respectively. Kaplan-Meier survival curve
      analysis showed a statistically significant initial survival with the first line
      EtoP cisplatin regimen for the initial 6 months of starting chemotherapy in
      comparison with the other regimens. CONCLUSIONS: This study showed a substantial
      pharmacoeconomic benefit with the cisplatin and etoposide chemo regimen in the
      lower socioeconomic group of patients. We believe that this is the first
      pharmacoeconomic study on metastatic non small cell lung treatment of great
      relevance to countries with limited resources.

PMID- 27051103
TI  - Household symptomatic contact screening of newly diagnosed sputum smears positive
      tuberculosis patients - An effective case detection tool.
AB  - OBJECTIVES: Primary objective was to assess the prevalence of tuberculosis (TB)
      among household contacts of newly diagnosed sputum smear (SS) positive TB index
      cases. Secondary objectives were the evaluation of risk factors in household
      contacts for acquiring TB disease; and the evaluation of various characteristics
      of index cases which influence the transmission of disease to household contacts.
      SETTINGS AND DESIGN: This exploratory cohort study included 521 household
      contacts of 133 newly diagnosed SS positive TB patients who were registered under
      the Revised National Tuberculosis Control Program at the Directly Observed
      Treatment-Short Course Centres of District Tuberculosis Centre, Kolhapur,
      Maharashtra from July 1, 2013 to February 28, 2014 (8 months). SUBJECTS AND
      METHODS: Household contacts with symptoms suggestive to TB were subjected to SS
      examination of two samples for acid fast bacilli by Ziehl-Neelsen staining and
      for X-ray chest postero-anterior view. Presence of risk factors in symptomatic
      contacts was also recorded. RESULTS: Eighteen contacts out of 521 (3.45%) had
      symptoms suggestive of TB. Of these, 6 contacts were diagnosed to have TB; 5
      being sputum positive cases and one with X-ray suggestive of TB; giving a
      prevalence of 1.15 %. The study achieved a yield of 4.51% secondary cases.
      CONCLUSIONS: Household contact screening of newly diagnosed TB index cases
      provides modest yield of cases. Relatively fewer secondary symptomatic persons
      need to be investigated by this method for achieving additional yield proving it
      to be a practical and feasible approach.

PMID- 27051104
TI  - Respiratory problems among cotton textile workers.
AB  - BACKGROUND: Long term occupational exposure to cotton dust is associated with
      respiratory symptoms and loss of pulmonary function. AIM: This study was
      conducted to explore respiratory symptoms, pulmonary function tests and chest
      radiography of workers, and to evaluate the findings of high resolution computed
      tomographyand its correlation with pulmonary function tests (PFT). MATERIAL AND
      METHODS: The study was conducted on 100 cotton workers as exposed group and 100
      unexposed subjects. Smokers were excluded from the study. All workers were
      interviewed and examined by the pulmonologist. PFT and chest radiography were
      conducted for all subjects. HRCT was performed for those with abnormal PFT or
      chest radiography. RESULTS: A total of 51% and 31% of the cotton textile workers
      had one or more respiratory symptoms and respiratory signs respectively. 28% of
      subjects in the exposed group and 5% of subjects in unexposed group had
      obstructive pattern. Bronchia wall thickening and air trapping were the most
      frequent chest radiography and HRCT abnormalities respectively. There was a
      significant correlation between HRCT and the results of PFT. CONCLUSION: We
      conclude that long term exposure to cotton dust is associated with obstructive
      disease that increase with duration of exposure (history of working years), also
      use of HRCT as a sensitive tool in the assessment of pathologic changes and it's
      correlation with PFT, confirms the expected pathophysiology of airway obstruction
      in cotton workers.

PMID- 27051105
TI  - Epidemiology of bronchial asthma in school children (10-16 years) in Srinagar.
AB  - OBJECTIVES: To assess the epidemiological profile of asthma in school going
      children in Srinagar, Kashmir. STUDY DESIGN: Cross-sectional study. SETTING:
      Thirty-one schools with proportionate representation from both government and
      private schools as well as from primary, middle, and high schools. PARTICIPANTS:
      School children aged 10-16 years with equal representation of sex and all ages.
      MAIN OUTCOME MEASURE: Prevalence of current and past asthma. METHODS AND RESULTS:
      After administering a modified pretested questionnaire, peak expiratory flow
      measurement was carried. Children who had asthma-like symptoms or positive family
      history of asthma or physician-labeled asthma were subjected to spirometry and
      bronchodilator reversibility. Out of 806 children, bronchial asthma was seen in
      60 (prevalence of 7.4%) which included 34 boys and 26 girls. Majority of
      asthmatic children (78.3% [n = 47]) had probable asthma; 6.7% (n = 4) had
      definite asthma; and 15% (n = 9) had physician-diagnosed asthma. Majority of
      children had intermittent asthma (78.3% [n = 47]). Mild persistent asthma was
      seen in 12.7% (n = 7) and 10% (n = 6) had moderate persistent asthma. None of the
      children had severe persistent asthma. The prevalence of current asthma was 3.2%
      (n = 26). On univariate analysis, the factors found to be statistically
      significant were family history of asthma (odds ratio [OR] =8.174; confidence
      interval [CI] =4.403-15.178), seasonal cough (OR = 4.266; CI = 2.336-7.791),
      allergic rhinitis (OR = 2.877; CI = 1.414-5.852), atopic dermatitis (OR = 6.597;
      CI = 2.72-16.004), and obesity (OR = 6.074; CI = 2.308-18.034). On multivariate
      analysis, family history, seasonal cough, allergic rhinitis, atopic dermatitis,
      and obesity were found to be significant independent risk factors. CONCLUSIONS:
      Srinagar qualifies as a low prevalence area for bronchial asthma in the age group
      of 10-16 years. Majority of children had mild intermittent asthma resulting in
      under diagnosis and wrong treatment.

PMID- 27051106
TI  - Prevalence of psychiatric comorbidities in chronic obstructive pulmonary disease
      patients.
AB  - INTRODUCTION: Psychiatric disorders, especially anxiety and depression have been
      reported to have an increased prevalence in chronic obstructive pulmonary disease
      (COPD) patients, but there is a paucity of data from India. AIMS AND OBJECTIVES:
      Aim of our study is to study the frequency of psychiatric comorbidities in COPD
      patients and their correlation with severity of COPD, as per global initiative
      for obstructive lung disease guidelines. MATERIALS AND METHODS: This study was
      conducted in outpatient department of a tertiary care hospital (King George's
      Medical University). A total of 74 COPD patients were included in this study and
      compared with 74 controls. The diagnosis and severity of COPD were assessed by
      spirometry. Psychiatric comorbidities were assessed using the Mini International
      Neuropsychiatric Interview questionnaire. RESULTS: The frequency of psychiatric
      comorbidities was significantly higher (P < 0.05) in COPD patients (28.4%) as
      compared to controls (2.7%). As regards to severity, the frequency was
      significantly increased in severe and very severe COPD. The frequency of
      psychiatric comorbidities in COPD patients increased significantly with the
      increase in duration of symptoms being present in 67% of patients with duration
      of symptoms more than 10 years and only 23% of patients with duration of symptoms
      <=5 years. CONCLUSION: The frequency of psychiatric comorbidities is increased in
      COPD patients as compared to controls. We recommend that all patients with COPD
      should be screened for psychiatric comorbidity, if any.

PMID- 27051108
TI  - Tubercular mycotic aortic aneurysm: A case report.
AB  - Tubercular aneurysms of larger vessels, particularly the aorta is very rare. The
      first case of tubercular involvement of the aorta in the form of aortitis was
      reported in 1882 by Weigert and the first case of tubercular mycotic aneurysm of
      the aorta was reported in 1895. The preoperative diagnosis of tubercular aortic
      aneurysm is difficult. Even at surgery, determining the tubercular nature of the
      lesion is problematic. The gross appearance may not be distinctive, and acid-fast
      stains are unlikely to be performed. We report the case of a young female patient
      who was started on antitubercular treatment for pleural effusion and was found to
      have aortic aneurysm, which later on proved to be tubercular in origin. 

PMID- 27051107
TI  - Cystic pulmonary hydatidosis.
AB  - Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by the larval
      stages of the cestode Echinococcus granulosus. Worldwide, pulmonary hydatid cyst
      is a significant problem medically, socially, and economically. Surgery is the
      definitive therapy of pulmonary hydatidosis. Benzimidazoles may be considered in
      patients with a surgical contraindication. This review will focus on
      pathogenesis, lifecycle, clinical features, and management of pulmonary hydatid
      disease. 

PMID- 27051110
TI  - Ganglioneuroblastoma: Unusual presentation as a pleural mass mimicking
      mesothelioma.
AB  - Ganglioneuroblastoma (GNB) is a rare peripheral neuroblastic tumor that is
      derived from developing neuronal cells of the sympathetic nervous system, and
      usually occurs in young children. We present a case of GNB occurring as pleural
      mass in a 2-year-old boy, which led to diagnostic confusion. On fine-needle
      aspiration cytology (FNAC), it was misinterpreted as mesothelioma. He underwent
      thoracotomy with excision of the mass. Histopathological findings showed features
      of a biphasic tumor suggestive of mesothelioma. Immunohistochemistry (IHC)
      performed for mesothelioma markers were inconclusive. On review of the histology
      slides, GNB was considered, which was subsequently proven by IHC. The rarity of
      this tumor, along with its nearly restricted occurrence at a young age,
      necessitates a strong suspicion in patients presenting with a symptomatic
      intrathoracic mass. 

PMID- 27051109
TI  - Askin tumor: A rare neoplasm of thoracopulmonary region.
AB  - Askin tumor is a rare neoplasm of thoracopulmonary region. But it mimics other
      common pediatric disorders, such as empyema, lymphoma, and tuberculosis, posing a
      great diagnostic and therapeutic challenge to the treating clinicians. So it is
      of utmost importance to make an early diagnosis and proper referral/treatment in
      such cases. We highlighted diagnostic challenge, treatment, and favorable outcome
      of a case that presented to us. 

PMID- 27051111
TI  - Salvage pneumonectomy for pulmonary arteriovenous malformation in a 12-year-old
      boy with brain abscess and hemiparesis: A fatal outcome.
AB  - Large pulmonary arteriovenous malformations (PAVMs) constitute an uncommon cause
      of central cyanosis with septic embolism and brain abscess. This large right to
      left shunt can lead to chronic severe hypoxemia and significant morbidity and
      mortality if untreated. Conservative parenchyma-sparing lung resection was used
      widely as treatment of choice. However, with the advent of embolotheraphy, it is
      considered the preferred mode of treatment with less invasiveness. We here report
      a 12-year-old boy with large aneurysmal pulmonary arteriovenous fistula presented
      with brain abscess and hemiparesis. He underwent thoracotomy and pneumonectomy
      for large PAVMs, and it was complicated with bleeding and massive blood
      transfusion. The patient developed acute renal failure as a postoperative
      complication and succumbed to it. We suggest proper look out for systemic
      collateral and their management by embolitheraphy either alone or in combination
      should be tried first. We also suggest median sternotomy and intrapericardial
      approach for pneumonectomy in such difficult situation can be helpful. 

PMID- 27051112
TI  - Left lung agenesis discovered by a spontaneous pneumothorax in a 20-year-old
      girl.
AB  - Lung agenesis is a rare condition which prognosis widely depends on associated
      malformations. Clinical presentation is so variable and diagnosis is often made
      in childhood. Here, we present a case of a 20-year-old girl who was admitted
      because of a spontaneous pneumothorax. Explorations concluded at a left lung
      agenesis, a hyperinflated right lung crossing the midline with a corresponding
      pneumothorax. There was no malformation else. This congenital condition and
      treatment for this rare presentation are discussed in detail. 

PMID- 27051113
TI  - Pyopneumothorax with Stocker type III congenital cystic adenomatoid malformation
      in a 5-month-old infant.
AB  - Congenital cystic adenomatoid malformation (CCAM) is a rare, developmental,
      hamartomatous abnormality of the lung characterized by a cessation of normal
      bronchiolar maturation, resulting in cystic overgrowth of the terminal
      bronchioles. We report one such case of CCAM in a 5-month-old female infant who
      was in perfect health until she suffered from spontaneous pyopneumothorax with
      type III CCAM of the lung and recovered after lobectomy. 

PMID- 27051114
TI  - Use of radial probe endobronchial ultrasound for the diagnosis of peripheral
      pulmonary lesion: First report from India.
AB  - Radial probe endobronchial ultrasound (EBUS) helps in the evaluation and sampling
      of peripheral pulmonary lesions (nodules, masses, consolidation), and has been
      demonstrated a safer alternative to computed tomography guided procedure,
      especially in lesions that are away from the chest wall. Although radial probe
      EBUS has been available for more than two decades, there is no report from the
      Indian subcontinent. Herein, we describe two cases of peripheral lung lesions
      that were successfully sampled with the use of radial probe EBUS. 

PMID- 27051115
TI  - Transcutaneous closure of chronic broncho-pleuro-cutaneous fistula by duct
      occluder device.
AB  - Bronchopleural fistula (BPF) is a well known complication of several pulmonary
      conditions posing challenging management problem and is often associated with
      high morbidity and mortality. Though no consensus exists on a definite closure
      management algorithm, strategies for closure widely include various methods like
      tube thoracostomy with suction, open surgical closure, bronchoscopy directed
      glue, coiling and sealants which now also includes use of occlusion devices. We
      report a case in which a novel method of delivery and closure of recurrent post
      operative broncho-pleuro-cutaneous fistula by a duct occluder device was done
      transcutaneously which has not been previously described in literature. 

PMID- 27051116
TI  - Swine flu fibrosis: Regressive or progressive?
AB  - Swine flu influenza had spread the world over in 2009. The main pathology was
      bilateral pneumonia. Majority of these cases recovered from pneumonia fully.
      Though in some cases, pulmonary fibrosis was reported as a sequel. However, long
      term progression of such pulmonary fibrosis is uncertain. We are hereby reporting
      two cases of swine flu that showed residual pulmonary fibrosis. The clinical and
      laboratory parameters were also recorded. In both the cases, radiological shadows
      and spirometric values did not show deterioration. We conclude that swine flu
      pulmonary fibrosis is not a progressive condition. 

PMID- 27051117
TI  - Parasitic infestation of lung: An unusual cause of interstitial pneumonitis.
AB  - Parasite infections are increasing worldwide due to increasing migration and
      traveling. Parasitic infections can affect lungs and present as a focal or
      diffuse lung diseases. High index of suspicion and detailed history are most
      important. We present a case of interstitial pneumonitis caused by parasite
      infestation, which was diagnosed on transbronchial lung biopsy. 

PMID- 27051118
TI  - Combined tracheoinnominate artery fistula and tracheoesophageal fistula: A very
      rare complication of indwelling tracheostomy tube.
AB  - Tracheoinnominate artery fistula (TIF) is a serious complication of tracheostomy.
      If untreated, it could be life-threatening. The emergency approach to the
      condition that includes prompt diagnosis, rapid control of bleeding with a clear
      airway, and operation with or without interruption of the innominate artery are
      the most important factors influencing patient outcome. Tracheoesophageal fistula
      (TEF) is another complication of tracheostomy. In association with compromised
      quality of life, this condition is really hard to be treated. We report a case of
      combined TIF and TEF in a 27-year-old man with quadriplegia who suffered a car
      accident but was successfully managed with interruption and ligature of the
      innominate artery repair of trachea. 

PMID- 27051119
TI  - Interstitial pneumonia associated to peginterferon alpha-2a: A focus on lung
      function.
AB  - Pulmonary toxicity related to the use of pegylated interferon alpha-2a during
      treatment of hepatitis C infections is rare; nonetheless, some cases with fatal
      outcomes have been reported. Evaluating patients' pulmonary function is a key to
      diagnosis, follow-up and prognosis of several respiratory diseases, but case
      reports of respiratory manifestations related to the use of pegylated interferon
      alpha-2a have limited their findings to only baseline measurements. This paper
      examines the case of a 65-year-old woman with chronic hepatitis C virus infection
      who developed interstitial pneumonitis associated with pegylated interferon alpha
      2a. Initial lung function evaluation revealed a marked reduction compared to an
      earlier assessment; the results were consistent with a moderate restricted
      pattern. Fortunately, over the ensuing 8 weeks of follow-up after discontinuing
      the drug, the patient recovered her lung function and experienced an overall
      improvement in her respiratory symptoms. 

PMID- 27051120
TI  - Tuberculosis and pulmonary hypertension: Commentary.

PMID- 27051121
TI  - Asymptomatic man with a large lung cyst.

PMID- 27051122
TI  - Blunt head and neck trauma: Interesting chest tomographic "effect".

PMID- 27051123
TI  - An uncommon congenital anomaly of the ribs.
AB  - Intrathoracic rib is an extremely rare congenital anomaly of the ribs. Here, we
      present the case of a 10-year-old boy with asthma who, on routine evaluation, was
      found to have this anomaly. 

PMID- 27051124
TI  - A rare cause of pulmonary hemorrhage in an infant.

PMID- 27051125
TI  - A massive intrathoracic mass lesion due to giant cell tumor of pleura.

PMID- 27051126
TI  - Superior vena cava syndrome as a clinical manifestation of recurrent cervical
      cancer.

PMID- 27051127
TI  - Transbronchial lung biopsy with a flexible cryoprobe during rigid bronchoscopy:
      Standardizing the procedure.

PMID- 27051128
TI  - Averting the legacy of kidney disease: Focus on childhood.

PMID- 27051129
TI  - Kidneys - kindergarten to graduation.

PMID- 27051130
TI  - Immunological risk assessment and human leukocyte antigen antibody testing in
      kidney transplantation.

PMID- 27051131
TI  - Recent advances in anti-neutrophil cytoplasmic antibody-associated vasculitis.
AB  - Anti-neutrophil cytoplasmic antibody-associated vasculitis is an uncommon
      inflammatory disease of small to medium-sized vessels that frequently presents
      with rapidly progressive glomerulonephritis and renal failure though it can
      affect any organ system. If untreated, the vast majority of patients will die
      within a year. Current treatments improve prognosis but affected patients remain
      at a substantially higher risk of death and adverse outcomes. We review the
      classification of the disease, our understanding of the pathogenesis and
      epidemiology, and propose future directions for research. We also evaluate the
      evidence supporting established treatment regimens and the progress of clinical
      trials for newer treatments to inform the design of future studies. 

PMID- 27051132
TI  - Carotid intima-media thickness as a marker of atherosclerosis in hemodialysis
      patients.
AB  - Atherosclerotic changes in carotid arteries of hemodialysis (HD) patients reflect
      global atherosclerotic changes in vasculature. Carotid intima-media thickness
      (CIMT) can be used for atherosclerosis prediction and assessment of
      cardiovascular risks in HD patients, and thus screening high-risk patients. In
      this cross-sectional study, CIMT was measured using ultrasonography (B-mode with
      5-10-MHz multifrequency linear probe) in HD patients in our hospitals.
      Additionally, we assessed the relationship between their CIMT and some
      cardiovascular risk factors. A total of 62 HD patients (64.5% male) were
      included. Age, body mass index, low-density lipoprotein, fasting blood sugar,
      history of diabetes mellitus and cardiovascular disease, serum albumin, and
      duration and adequacy of HD in study patients had significant association with
      their CIMT. There were no significant relationships between CIMT and patient's
      gender, smoking, serum calcium, phosphate, calcium x phosphate product,
      hemoglobin, and uric acid level. More diagnostic modalities must be performed for
      detecting the impact of atherosclerosis on HD patients with high CIMT. 

PMID- 27051133
TI  - Color-Doppler sonographic tissue perfusion measurements reveal significantly
      diminished renal cortical perfusion in kidneys with vesicoureteral reflux.
AB  - Vesicoureteral reflux (VUR) and its sequelae may lead to reduced renal perfusion
      and loss of renal function. Methods to describe and monitor tissue perfusion are
      needed. We investigated dynamic tissue perfusion measurement (DTPM) with the
      PixelFlux-software to measure microvascular changes in the renal cortex in 35
      children with VUR and 28 healthy children. DTPM of defined horizontal slices of
      the renal cortex was carried out. A kidney was assigned to the "low grade reflux"
      group if the reflux grade of the voiding cystourethrogram was 1 to 3 and to the
      "high grade reflux"-group if the reflux grade was 4 to 5. Kidneys with VUR showed
      a significantly reduced cortical perfusion. Compared to healthy kidneys, this
      decline reached in low and high grade refluxes within the proximal 50% of the
      cortex: 3% and 12 %, in the distal 50% of the cortex: 21% and 44 % and in the
      most distal 20 % of the cortex 41% and 44%. DTPM reveals a perfusion loss in
      kidneys depending on the degree of VUR, which is most pronounced in the
      peripheral cortex. Thus, DTPM offers the tool to evaluate microvascular
      perfusion, to help planning treatment decisions in children with VUR. 

PMID- 27051134
TI  - Long-term prognosis of IgA nephropathy presenting with minimal or no proteinuria:
      A single center experience.
AB  - The long-term prognosis of patients with IgA nephropathy (IgAN) who present with
      preserved renal function and minimal proteinuria is not well described. We
      investigated the long-term outcomes of IgAN patients with an apparently benign
      presentation and evaluated prognostic factors for renal survival and clinical
      remission. We studied Japanese patients with biopsy-proven IgAN who had an
      estimated glomerular filtration rate (eGFR) >=60 mL/min/1.73 m(2) and proteinuria
      <0.5 g/day at the time of renal biopsy. The renal biopsies were reviewed using
      the Oxford classification. Twenty patients met the inclusion criteria. At
      diagnosis, the median eGFR (interquartile range) was 76.8 (65.2-91.1) mL/min/1.73
      m(2), and the median proteinuria level was 0.31 (0.16-0.39) g/day. Only one
      patient had an increase in serum creatinine of over 50% and no patient progressed
      to end-stage renal disease. The 15-year renal survival rate was 93.8%. Clinical
      remission was observed in 9 (45%) patients. Baseline proteinuria was the only
      factor significantly associated with the absence of clinical remission. The long
      term prognosis of Japanese patients with IgAN who presents with minor urinary
      abnormalities and preserved renal function is excellent. 

PMID- 27051135
TI  - ABO-incompatible renal transplantation in developing world - crossing the
      immunological (and mental) barrier.
AB  - ABO incompatibility has been considered as an important immunological barrier for
      renal transplantation. With the advent of effective preconditioning protocols, it
      is now possible to do renal transplants across ABO barrier. We hereby present a
      single center retrospective analysis of all consecutive ABOi renal transplants
      performed from November 2011 to August 2014. Preconditioning protocol consisted
      of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and
      maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and
      prednisolone. The outcome of these ABOi transplants was compared with all other
      consecutive ABO-compatible (ABOc) renal transplants performed during same time.
      Twenty ABOi renal transplants were performed during the study period. Anti-blood
      group antibody titer varied from 1:2 to 1:512. Patient and graft survival was
      comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was
      15% in ABOi group, which was similar to ABOc group (16.29%). There were no
      antibody-mediated rejections in ABOi group. The infection rate was also
      comparable. We conclude that the short-term outcome of ABOi and ABOc transplants
      is comparable. ABOi transplants should be promoted in developing countries to
      expand the donor pool. 

PMID- 27051136
TI  - Clinical utility of urine neutrophil gelatinase-associated lipocalin measured at
      admission to predict outcomes in heterogeneous population of critically ill
      patients.
AB  - Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a reliable early
      biomarker of acute kidney injury (AKI) in a homogeneous patient population.
      However, its utility in a heterogeneous population of critically ill, in whom the
      time of onset of renal insult is often unclear, is not clearly established. We
      evaluated the ability of a single measurement of uNGAL in a heterogeneous adult
      population, on admission to intensive care unit (ICU), to predict the occurrence
      of AKI and hospital mortality. One hundred and two consecutive adult patients had
      uNGAL measured within 8 h of admission to ICU. The demographic and laboratory
      data were collected at admission. The diagnosis of AKI was based on AKI Network
      (AKIN) criteria. The primary outcome was the development of AKI, and the
      secondary outcome was hospital mortality. The mean age was 54 +/- 16.4 years and
      65% were males. Urine NGAL (ng/ml) was 69 +/- 42 in patients with AKI (n = 42)
      and 30.4 +/- 41.7 in those without AKI (P < 0.001). The area under the receiver
      operating characteristic (ROC) curve for prediction of AKI was 0.79 and for serum
      creatinine (SCr) was 0.88. The sensitivity and specificity for a cut-off value of
      uNGAL of 75 ng/ml to predict AKI were 0.5 and 0.85 respectively. uNGAL > 75 ng/ml
      was a strong (odd ratio = 5.17, 95% confidence interval: 1.39-19.3) and
      independent predictor of hospital mortality. A single measurement of uNGAL at
      admission to ICU exhibited good predictive ability for AKI though the sensitivity
      was low. The predictive ability of uNGAL was inferior to simultaneously measured
      SCr at admission, hence limited its clinical utility to predict AKI. However,
      admission uNGAL was a strong, independent predictor of hospital mortality. 

PMID- 27051137
TI  - Neutrophil gelatinase-associated lipocalin as a biomarker of disease progression
      in patients with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with early mortality, decreased
      quality of life and increased health care expenditures. The aim of this study was
      to determine whether or not urinary NGAL (uNGAL) level is associated with renal
      damage and kidney disease progression in patients with CKD and to evaluate the
      predictive value of uNGAL in progression of CKD. Totally, 91 cases of CKD stage
      II, III, IV, and 50 age-matched healthy controls were enrolled. The follow-up end
      point was 18 months; end-point of the study was progression to an estimated
      glomerular filtration rate (eGFR) of <15 ml/min and/or CKD stage V. Forty-five
      cases (49.4%) were progressors and 46 were nonprogressors. uNGAL levels were
      significantly higher in CKD subjects as compared to healthy controls (log 1.09 +/
      0.22 MUg/ml in controls versus log 1.22 +/- 2.08 MUg/ml in stage II, log 3.34 +/
      2.74 MUg/ml in stage III and log 3.70 +/- 0.18 MUg/ml in stage IV). Univariate
      Cox proportional hazards model showed that only eGFR (hazard ratio [HR]: 0.95;
      95% confidence interval [CI]: 0.93-0.96; P < 0.001) and uNGAL (HR: 1.11; 95% CI:
      1.01-1.20; P < 0.001) were significantly associated with end-point of CKD stage
      V, but multiple Cox proportional regression model showed significant association
      of uNGAL (HR: 1.11; 95% CI: 1.01-1.20; P < 0.001) and eGFR (HR: 0.962, 95% CI:
      0.95-0.98; P < 0.001) with end-point of CKD stage V. This suggests that uNGAL
      would not be a simple surrogate index of baseline eGFR, but a marker of CKD
      progression beyond the information provided by eGFR estimation. 

PMID- 27051138
TI  - Angiomyolipoma of donor kidney: Successful transplantation and 5-year follow-up.
AB  - Angiomyolipomas (AML) of the kidney are non-encapsulated benign neoplasms with
      the incidence of 45-80% in patients with tuberous sclerosis and 1-3% in sporadic
      cases. There are very few case reports in the literature in which kidneys with
      AML have been used for transplantation. We report here a 27-year-old female
      patient who received a live related renal transplant from her mother with
      isolated angiomyolipoma in donor kidney and on follow-up after 5 years, has
      stable graft function and tumor size. 

PMID- 27051139
TI  - Nonspecific positivity on the Luminex crossmatch assay for anti-human leukocyte
      antigen antibodies due to antibodies directed against the antibody coated beads.
AB  - Two cases are described of previously unreported false positivity on the Luminex
      crossmatch assay due to non HLA specific antibodies directed against the beads.
      In both cases the Luminex crossmatch indicated the presence of donor specific
      antibodies to class II HLA antigens, which was not substantiated by the clinical
      scenario or other assays. We could demonstrate the non specificity of these
      antibodies through using the same assay in a modified form where beads were
      unexposed to cell lysate and therefore did not carry HLA antigens at all. These
      cases further serve to emphasize the absolute necessity of correlating positive
      results with the priming history, and confirming their relevance using other
      platforms. 

PMID- 27051140
TI  - Collapsing glomerulopathy in a case of anti-neutrophil cytoplasmic antibody
      associated vasculitis.
AB  - Collapsing glomerulopathy (CG) is a pathological entity characterized by collapse
      and wrinkling of glomerular tuft, podocyte dedifferentiation and hyperplasia. CG
      may be idiopathic or secondary to other diseases. CG has been described with IgA
      nephropathy, membranous glomerulopathy, diabetic nephropathy, and lupus
      nephritis. However, till date there is no report of CG in association with the
      anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Here, we
      present a case of CG that developed during follow-up in a case of AAV with biopsy
      proven pauci-immune glomerulonephritis. 

PMID- 27051141
TI  - Eosinophilic granulomatosis with polyangiitis with severe pulmonary hemorrhage
      treated with rituximab.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by systemic
      vasculitis, asthma and eosinophilia. Severe pulmonary hemorrhage is rare. Renal
      involvement is seen in approximately 25% and can vary from isolated urinary
      abnormality to rapidly progressive glomerulonephritis. There is limited evidence
      to support the use of rituximab in this condition. We present a patient with EGPA
      who had severe pulmonary hemorrhage and rapidly progressive glomerulonephritis.
      He responded to standard treatment including prednisolone, cyclophosphamide, and
      plasma exchange. He subsequently had a relapse of pulmonary hemorrhage that was
      treated successfully with rituximab. 

PMID- 27051142
TI  - Idiopathic nodular glomerulosclerosis: Report of two cases and review of
      literature.
AB  - Nodular glomerulosclerosis, a pathological finding characterized by areas of
      marked mesangial expansion with accentuated glomerular nodularity can be seen in
      a number of conditions including diabetic nephropathy, amyloidosis, light chain
      deposition disease, fibrillary and immunotactoid glomerulopathy, collagen type
      III disease, nodular membranoproliferative glomerulonephritis, and Takayasu's
      arteritis. Idiopathic nodular glomerulosclerosis is a diagnosis of exclusion and
      is reported in patients with hypertension, smoking, chronic obstructive pulmonary
      disease, obesity, metabolic syndrome, etc. We report two cases of idiopathic
      nodular glomerulosclerosis, one in obese hypertensive male and the other in
      nonhypertensive, nonobese female patient. 

PMID- 27051143
TI  - Renal tuberculosis with lobar calcification.

PMID- 27051144
TI  - Susceptibility weighted imaging: An important tool for early diagnosis of
      tacrolimus toxicity.

PMID- 27051145
TI  - Assessment of burden among caregivers of hemodialysis patients at a Tertiary Care
      Hospital of Andhra Pradesh.

PMID- 27051146
TI  - Effect of inflammation on nutritional status of patients on maintenance
      hemodialysis.

PMID- 27051147
TI  - Peritonitis due to Streptococcus gordonii in a patient treated with continuous
      ambulatory peritoneal dialysis.

PMID- 27051148
TI  - Molecular functional imaging in personalized clinical oncology: The road less
      traveled.

PMID- 27051149
TI  - Prostate cancer is not breast cancer.
AB  - Cancers of the prostate and breast are hormone dependent cancers. There is a
      tendency to equate them and apply same algorithms for treatment. It is pointed
      out that metastatic prostate cancer with bone-only disease is a potentially fatal
      condition with a much poorer prognosis than metastatic breast cancer and needs a
      more aggressive approach. 

PMID- 27051150
TI  - Diabetes, Epstein-Barr virus and extranodal natural killer/T-cell lymphoma in
      India: Unravelling the plausible nexus.
AB  - The International Diabetes Federation Diabetes Atlas estimates a staggering 590
      million people affected with diabetes mellitus (DM) within the next two decades
      globally, of which Type 2 DM will constitute more than 90%. The associated
      insulin resistance, hyperinsulinemia, and hyperglycemia pose a further
      significant risk for developing diverse malignant neoplasms. Diabetes and
      malignancy are multifactorial heterogeneous diseases. The immune dysfunction
      secondary to Type 2 diabetes also reactivates latent infections with high
      morbidity and mortality rates. Epstein-Barr virus (EBV), a ubiquitous human
      herpes virus-4, is an oncogenic virus; its recrudescence in the immunocompromised
      condition activates the expression of EBV latency genes, thus immortalizing the
      infected cell and giving rise to lymphomas and carcinomas. Extranodal natural
      killer/T-cell lymphoma (ENKTCL), common in South-East Asia and Latin America; is
      a belligerent type of non-Hodgkin lymphoma (NHL) almost invariably associated
      with EBV. An analysis of articles sourced from the PubMed database and Google
      Scholar web resource until February 2014, suggests an increasing incidence of NHL
      in Asia/India and of ENKTCL in India, over the last few decades. This article
      reviews the epidemiological evidence linking various neoplasms with Type 2 DM and
      prognosticates the emergence of ENKTCL as a common lymphoreticular malignancy
      secondary to Type 2 diabetes, in the Indian population in the next few decades. 

PMID- 27051151
TI  - Vitamin D insufficiency among children with cancer in India.
AB  - BACKGROUND: Vitamin D plays an important role in regulating various homeostatic
      mechanisms and has yet untapped potential in cancer prevention and prognosis.
      Only a few studies have been done worldwide in relating the Vitamin D levels in
      pediatric cancer patients to the general population but none so far in an Indian
      setting to the best of our knowledge. OBJECTIVE: To compare the Vitamin D levels
      in a group of children with cancer to that of the general pediatric population
      and to note differences in the prevalence of Vitamin D insufficiency and make
      inferences arising from demographic and therapeutic variations. MATERIALS AND
      METHODS: Vitamin D levels were found by immuno-chemilumino-metric assay in 102
      children (51 cases and 51 controls) over a 6 months period. RESULTS: In comparing
      the Vitamin D levels of children with cancer and controls from a healthy
      population we found an increased incidence of Vitamin D insufficiency in cancer
      children (80.39%) when compared to controls (50.98%) and a much lower mean
      Vitamin D value in cancer children (22.8 ng/ml) when compared to controls (33
      ng/dl). It was also found that cancer children above 6 years had a greater chance
      for developing Vitamin D insufficiency (P = 0.038) as did children suffering from
      hematological malignancies (P = 0.025). CONCLUSION: Our study showed an increased
      prevalence of Vitamin D insufficiency in children with cancer and hence we
      suggest routine measurement of Vitamin D levels in children with cancer and
      subsequent supplementation.

PMID- 27051152
TI  - Bacteriological profile and antibiotic susceptibility patterns of clinical
      isolates in a tertiary care cancer center.
AB  - INTRODUCTION: This increased risk of bacterial infections in the cancer patient
      is further compounded by the rising trends of antibiotic resistance in commonly
      implicated organisms. In the Indian setting this is particularly true in case of
      Gram negative bacilli such as Escherichia coli, Klebsiella pneumoniae and
      Acinetobacter spp. Increasing resistance among Gram positive organisms is also a
      matter of concern. The aim of this study was to document the common organisms
      isolated from bacterial infections in cancer patients and describe their
      antibiotic susceptibilities. METHODS: We conducted a 6 month study of all
      isolates from blood, urine, skin/soft tissue and respiratory samples of patients
      received from medical and surgical oncology units in our hospital. All samples
      were processed as per standard microbiology laboratory operating procedures.
      Isolates were identified to species level and susceptibility tests were performed
      as per Clinical Laboratory Standards Institute (CLSI) guidelines -2012. RESULTS:
      A total of 285 specimens from medical oncology (114) and surgical oncology
      services (171) were cultured. Escherichia coli, Klebsiella pneumoniae,
      Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter spp. were most
      commonly encountered. More than half of the Acinetobacter strains were resistant
      to carbapenems. Resistance in Klebsiella pneumoniae to cephalosporins,
      fluoroquinolones and carbapenems was >50%. Of the Staphylococcus aureus isolates
      41.67% were methicillin resistant. CONCLUSION: There is, in general, a high level
      of antibiotic resistance among gram negative bacilli, particularly E. coli,
      Klebsiella pneumoniae and Acinetobacter spp. Resistance among Gram positives is
      not as acute, although the MRSA incidence is increasing.

PMID- 27051153
TI  - Retrospective analysis of patients with carcinoma cervix in a rural/semi-urban
      setting in Western India.
AB  - OBJECTIVES: To compare the presentation of cervical cancer and the treatment
      modalities received by the patients at a semi-urban/rural area of Western India
      with that of published literature from urban centers. MATERIALS AND METHODS: We
      conducted a retrospective analysis of patients with cervical cancer who presented
      at a semi-urban/rural cancer center between 2010 and 2013. A total of 141
      patients with the median age of 51 years (25-81) were studied. The demographic
      and clinical variables included age, annual family income, profession,
      comorbidities, baseline hemoglobin, prior screening, clinical stage, treatment
      administered, and complications. The pathological variables included tumor type
      and grade. RESULTS: In our study, all patients presented with vaginal bleeding.
      Majority of the patients (51 patients, 37.7%) had Stage 3B disease. Since
      majority presented at later stages (Stage 3B), chemotherapy-radiotherapy was the
      most common treatment modality used in our population. On histopathology, 127
      patients (90%) had squamous cell carcinoma while 14 patients (10%) had
      adenocarcinoma. In 96 patients (68%), the tumor grade was not known while it was
      a high, intermediate, and low grade in 6 (4%), 18 (13%), and 21 (15%) patients,
      respectively. The follow-up data of our study were not adequate; hence, the long
      term survival results could not be presented. CONCLUSION: Patients in rural India
      setting present at later stages which could be improved by creating awareness,
      improving their personal hygiene, and adequate screening.

PMID- 27051154
TI  - Gestational trophoblastic neoplasia, management as per risk stratification in a
      developing country.
AB  - AIMS: The purpose of this analysis was to address the outcome of GTN from a
      tertiary care centre of India. MATERIALS AND METHODS: We undertook a
      retrospective and prospective review of GTN cases treated at our centre from 2006
      to 2014. Patients of GTN were assigned to low-risk or high-risk categories as per
      the FIGO scoring system. The low-risk group was treated with combination of
      actinomycin-D and methotrexate (MTX) and the high-risk group received the EMA/CO
      regimen. Salvage therapy was EP/TP. Treatment was continued for 3 cycles after
      normalization of beta-hCG level, after which the patients were kept on follow-up.
      RESULTS: In total, 52 GTN patients were treated at our institution during this
      period; 21 were low-risk and 31 were in the high-risk category. The lung was the
      most common site of metastasis. All low risk patients achieved complete
      remission. Among high risk patients one patient died while receiving first cycle
      chemotherapy, one patient relapsed and 29 patients achieved complete remission.
      The single relapsed patient also achieved remission with 2nd line chemotherapy.
      CONCLUSION: 1. Two drug combination of Actinomycin-D and Methotrexate is a better
      alternative to single drug chemotherapy especially in developing countries were
      proper risk stratification is not always possible. 2. Patients with high disease
      burden should initially be treated with low dose chemotherapy to avoid life
      threatening visceral haemorrhage.

PMID- 27051155
TI  - Trends in management of acute lymphoblastic leukemia: Influence of insurance
      based healthcare and treatment compliance on the outcome of adolescents and
      adults with acute lymphoblastic leukemia.
AB  - AIM: In this study, we attempted to analyze the impact of insurance based health
      care system and treatment compliance on the outcome of adolescent and adults with
      acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Patients who underwent
      treatment for ALL during the period 2003-2011 were enrolled into this
      retrospective study. Patients on supportive or palliative care only and patients
      with age <10 years were excluded. The hospital records and tumor registry records
      were studied. Patients were stratified into two groups, Group A (prior to the
      introduction of state health insurance [SHI], 2003-2007) and Group B (after the
      introduction of SHI, 2008-2011). Overall survival (OS) was calculated using
      Kaplan-Meier method. RESULTS: A total of 420 patients with suspected or confirmed
      ALL visited our center during the study period and 179 patients (87 in Group A
      and 92 in Group B) were considered for inclusion. The median age in years (range)
      was 18 (10-57) and 18 (10-58) respectively in Groups A and B with males more than
      females. Median OS (95% CI) was 9 (6.7-11.2) and 12 (7.3-16.7) months in the
      Groups A and B respectively (P = 0.265). Poor treatment compliance in both groups
      was high (36% in Group A and 41% in Group B, [P = 0.107]) with lower default
      rates in Group B (P = 0.019). Patients with good compliance in the total study
      population and the individual study groups had significantly better OS.
      CONCLUSIONS: Insurance based health care has improved outcomes in the present
      study but not compliance to treatment. Significantly better OS was observed in
      patients with good compliance.

PMID- 27051156
TI  - A report of the frequency of colorectal carcinoma and involved lymph nodes in
      South-West Iran.
AB  - CONTEXT: The colorectal cancer (CRC) is the most common malignancy between men
      and women. CRC has considerable morbidity and mortality, with more than 1000,000
      new cases and 500,000 annual deaths. Regional lymph nodes are most common sites
      of metastasis from colon cancer. Lymph node involvement is an essential factor in
      enabling the accurate evaluation of prognosis in CRC patients. AIMS: In this
      study, we focused on the frequency of CRC and involved lymph nodes and adequacy
      of lymph node dissection in patients who referred to the Oncology and
      Radiotherapy Department of Golestan Hospital in Ahvaz City located in South-West
      Iran. SETTING AND DESIGN: We conducted a retrospective study among patients
      receiving surgical treatment for CRC in the Department of Oncology and
      Radiotherapy of Golestan Hospital in Ahvaz City located in South-West Iran
      between 2001 and 2010. METHODS AND MATERIALS: All patients who underwent
      resection for CRC by open or laparoscopic approaches were included in the study.
      Data were collected from patients' medical records. STATISTICAL ANALYSIS USED:
      Statistical data were analyzed using SPSS 21. RESULTS: A total of 585 cases with
      CRC aged from16 to 89 years with mean age of 53-year-old were studied. Average
      number of dissected nodes was 8 lymph nodes, and lymph nodes were not found in
      pathology specimen of 61 cases (10.4%). In 199 patients (34.01%), number of
      dissected lymph nodes was 12 or more and in 386 patients (65.98%), number of
      dissected lymph nodes was <12. CONCLUSION: This study revealed a large amount of
      patients that had been under over treatment with radiotherapy and the following
      inability. Lack of removal of sufficient tissue by the surgeon during surgery or
      an inadequate sample check by a pathologist might lead to an inability to correct
      staging of the disease as well as the inability to determine the treatment
      program of the patients and over treatment with radiotherapy and chemotherapy.

PMID- 27051157
TI  - Chemotherapy-induced adverse drug reactions in oncology patients: A prospective
      observational survey.
AB  - BACKGROUND: Chemotherapy, a multimodal approach to oncological treatment,
      involves highly complex regimens and hence accounts to high susceptibility toward
      adverse drug reactions (ADRs). The present study aims to determine the prevalence
      of adverse events in patients treated with chemotherapy. MATERIALS AND METHODS:
      Spontaneous ADR report of patients on antineoplastic drugs received in the past 2
      years (January 2011-January 2013) were studied. These reports were analyzed for
      various carcinomas under treatment, medications used, types of ADRs, organ system
      involvement, severity, causality assessment, and preventability. RESULTS: Over a
      period of 2 years, a total 591 cases were received with an incidence of 58.6%.
      The prevalence of ADRs was more in female patients (73.6%) as compared to men.
      ADRs mostly occurred in the age group of 41-50 years (27.4%). Patients treated
      for breast carcinoma (39.1%) reported the highest incidence of ADRs. Cisplatin
      (19.6%) was found to be the most common offending drug. The most common ADR
      reported was nausea and vomiting (23%). Gastroenterology (40.1%) was the most
      affected system. About 50.2% of the ADRs required treatment and 12.9% ADRs were
      considered serious. Causality assessment revealed that 80% of the ADRs were
      possible. About 86.97% cases were found to be mild, and 51% were not preventable.
      CONCLUSION: The success of chemotherapy comes with the word of caution regarding
      toxicities of antineoplastic drugs. Pharmacovigilance of these drugs needs to be
      explored, and use of preventative measures needs to be enhanced in order to
      reduce the incidence and severity of ADRs.

PMID- 27051158
TI  - Fluorodeoxyglucose-positron emission tomography in carcinoma nasopharynx: Can we
      predict outcomes and tailor therapy based on postradiotherapy fluorodeoxyglucose
      positron emission tomography?
AB  - BACKGROUND: Positron emission tomography-computed tomography (PET-CT) is an
      emerging modality for staging and response evaluation in carcinoma nasopharynx.
      This study was conducted to evaluate the impact of PET-CT in assessing response
      and outcomes in carcinoma nasopharynx. MATERIALS AND METHODS: Forty-five patients
      of nonmetastatic carcinoma nasopharynx who underwent PET-CT for response
      evaluation at 10-12 weeks posttherapy between 2004 and 2009 were evaluated.
      Patients were classified as responders (Group A) if there was a complete response
      on PET-CT or as nonresponders (Group B) if there was any uptake above the
      background activity. Data regarding demographics, treatment, and outcomes were
      collected from their records and compared across the Groups A and B. RESULTS: The
      median age was 41 years. 42 out of 45 (93.3%) patients had WHO Grade 2B disease
      (undifferentiated squamous carcinoma). 24.4%, 31.1%, 15.6, and 28.8% patients
      were in American Joint Committee on Cancer Stage IIb, III, Iva, and IVb. All
      patients were treated with neoadjuvant chemotherapy followed by concomitant
      chemoradiotherapy. Forty-five patients, 28 (62.2%) were classified as responders,
      whereas 17 (37.8%) were classified as nonresponders. There was no significant
      difference in the age, sex, WHO grade, and stage distribution between the groups.
      Compliance to treatment was comparable across both groups. The median follow-up
      was 25.3 months (759 days). The disease-free survival (DFS) of the group was
      57.3% at 3 years. The DFS at 3 years was 87.3% and 19.7% for Group A and B,
      respectively (log-rank test, P < 0.001). Univariate and multivariate analysis
      revealed Groups to be the only significant factor predicting DFS (P value 0.002
      and < 0.001, respectively). In Group B, the most common site of disease failure
      was distant (9, 53%). CONCLUSION: PET-CT can be used to evaluate response and as
      a tool to identify patients at higher risk of distant failure. Further, this
      could be exploited to identify patients who may need treatment intensification.
      This needs to be validated prospectively.

PMID- 27051159
TI  - Voriconazole is a safe and effective anti-fungal prophylactic agent during
      induction therapy of acute myeloid leukemia.
AB  - BACKGROUND: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal
      infections (IFIs) during induction therapy of acute myeloid leukemia (AML).
      Posaconazole is considered the standard of care. Voriconazole, a generic cheaper
      alternative is a newer generation azole with broad anti-fungal activity. There is
      limited data on the use of voriconazole as a prophylactic drug. MATERIALS AND
      METHODS: A single-center, prospective study was performed during which patients
      with AML undergoing induction chemotherapy received voriconazole as AFP (April
      2012 to February 2014). Outcomes were compared with historical patients who
      received fluconazole as AFP (January 2011-March 2012, n = 66). RESULTS: Seventy
      five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1)
      received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI
      was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with
      respect to baseline characteristics. Voriconazole (when compared to fluconazole)
      reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to
      start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P <
      0.001) and delayed the start of therapeutic antifungals in those who needed it
      (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the
      use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not
      significant. Three patients discontinued voriconazole due to side-effects.
      CONCLUSION: Voriconazole is an effective and safe oral agent for IFI prophylaxis
      during induction therapy of AML. Availability of generic equivalents makes this a
      more economical alternative to posaconazole.

PMID- 27051160
TI  - Hodgkin lymphoma: A clinicopathological and immunophenotypic study.
AB  - INTRODUCTION: The diagnosis of Hodgkin lymphoma (HL) is defined in terms of its
      microscopic appearance (histology) and the expression of cell surface markers
      (immunophenotype). AIMS AND OBJECTIVES: This study aims to analyze the clinical
      features, histomorphology, and immunoprofile of over 200 patients of HL diagnosed
      over a period of 4 years at our institute and to determine relative frequency of
      various histological subtypes (based on WHO classification) in relation to age
      and sex distribution in this part of the country. MATERIALS AND METHODS: All HL
      cases diagnosed between January 2006 and December 2009 were retrieved from
      hospital records. The histopathology of both lymph node and bone marrow biopsy
      (where ever available) along with immunohistochemistry (CD15, CD30, CD20, and
      ALK) were reviewed. RESULTS: There was a bimodal age distribution. HL affected
      people a decade earlier than in the western population. The most common
      presenting complaint was cervical lymphadenopathy. Mixed cellularity was the most
      frequent subtype (67%), followed by nodular sclerosing subtype (23.5%). Group A
      (CD15+, CD30+, CD20-), which represents the archetypical immunophenotype of
      classical HL (CHL) was the most common type (60.6%). The number of CD15 negative
      CHL was 35.8% and CD20 positive CHL was 17.5%. CD15 negativity with CD20
      positivity was seen in 5% CHL. One out of seven CD20 positive CHL patients showed
      relapse. CONCLUSION: In this paper, we have discussed in detail about various
      clinical and histopathological parameters of HL and their relative frequency in
      various histological subtypes. This paper is being presented as it is a rather
      large study from India taking into consideration the clinical, pathologic, and
      immunophenotypic profile of the patients.

PMID- 27051161
TI  - Adenomatoid tumor of cervix: The first case report.

PMID- 27051162
TI  - Isolated bone marrow carcinomatosis: A rare presentation of poorly differentiated
      adenocarcinoma of the stomach in a young male.

PMID- 27051163
TI  - Ten years of online publication of Journal of Medical Physics.

PMID- 27051164
TI  - Computed tomography imaging parameters for inhomogeneity correction in radiation
      treatment planning.
AB  - Modern treatment planning systems provide accurate dosimetry in heterogeneous
      media (such as a patient' body) with the help of tissue characterization based on
      computed tomography (CT) number. However, CT number depends on the type of
      scanner, tube voltage, field of view (FOV), reconstruction algorithm including
      artifact reduction and processing filters. The impact of these parameters on CT
      to electron density (ED) conversion had been subject of investigation for
      treatment planning in various clinical situations. This is usually performed with
      a tissue characterization phantom with various density plugs acquired with
      different tube voltages (kilovoltage peak), FOV reconstruction and different
      scanners to generate CT number to ED tables. This article provides an overview of
      inhomogeneity correction in the context of CT scanning and a new evaluation tool,
      difference volume dose-volume histogram (DVH), dV-DVH. It has been concluded that
      scanner and CT parameters are important for tissue characterizations, but changes
      in ED are minimal and only pronounced for higher density materials. For lungs,
      changes in CT number are minimal among scanners and CT parameters. Dosimetric
      differences for lung and prostate cases are usually insignificant (<2%) in three
      dimensional conformal radiation therapy and < 5% for intensity-modulated
      radiation therapy (IMRT) with CT parameters. It could be concluded that CT number
      variability is dependent on acquisition parameters, but its dosimetric impact is
      pronounced only in high-density media and possibly in IMRT. In view of such small
      dosimetric changes in low-density medium, the acquisition of additional CT data
      for financially difficult clinics and countries may not be warranted. 

PMID- 27051165
TI  - Analysis of small field percent depth dose and profiles: Comparison of
      measurements with various detectors and effects of detector orientation with
      different jaw settings.
AB  - The advent of modern technologies in radiotherapy poses an increased challenge in
      the determination of dosimetric parameters of small fields that exhibit a high
      degree of uncertainty. Percent depth dose and beam profiles were acquired using
      different detectors in two different orientations. The parameters such as
      relative surface dose (D S), depth of dose maximum (D max), percentage dose at 10
      cm (D 10), penumbral width, flatness, and symmetry were evaluated with different
      detectors. The dosimetric data were acquired for fields defined by jaws alone,
      multileaf collimator (MLC) alone, and by MLC while the jaws were positioned at 0,
      0.25, 0.5, and 1.0 cm away from MLC leaf-end using a Varian linear accelerator
      with 6 MV photon beam. The accuracy in the measurement of dosimetric parameters
      with various detectors for three different field definitions was evaluated. The
      relative D S(38.1%) with photon field diode in parallel orientation was higher
      than electron field diode (EFD) (27.9%) values for 1 cm *1 cm field. An
      overestimation of 5.7% and 8.6% in D 10 depth were observed for 1 cm *1 cm field
      with RK ion chamber in parallel and perpendicular orientation, respectively, for
      the fields defined by MLC while jaw positioned at the edge of the field when
      compared to EFD values in parallel orientation. For this field definition, the in
      plane penumbral widths obtained with ion chamber in parallel and perpendicular
      orientation were 3.9 mm, 5.6 mm for 1 cm *1 cm field, respectively. Among all
      detectors used in the study, the unshielded diodes were found to be an
      appropriate choice of detector for the measurement of beam parameters in small
      fields. 

PMID- 27051166
TI  - Investigation of grid performance using simple image quality tests.
AB  - Antiscatter grids improve the X-ray image contrast at a cost of patient radiation
      doses. The choice of appropriate grid or its removal requires a good knowledge of
      grid characteristics, especially for pediatric digital imaging. The aim of this
      work is to understand the relation between grid performance parameters and some
      numerical image quality metrics for digital radiological examinations. The grid
      parameters such as bucky factor (BF), selectivity (Sigma), Contrast improvement
      factor (CIF), and signal-to-noise improvement factor (SIF) were determined
      following the measurements of primary, scatter, and total radiations with a
      digital fluoroscopic system for the thicknesses of 5, 10, 15, 20, and 25 cm
      polymethyl methacrylate blocks at the tube voltages of 70, 90, and 120 kVp. Image
      contrast for low- and high-contrast objects and high-contrast spatial resolution
      were measured with simple phantoms using the same scatter thicknesses and tube
      voltages. BF and SIF values were also calculated from the images obtained with
      and without grids. The correlation coefficients between BF values obtained using
      two approaches (grid parameters and image quality metrics) were in good
      agreement. Proposed approach provides a quick and practical way of estimating
      grid performance for different digital fluoroscopic examinations. 

PMID- 27051167
TI  - Application of Chang's attenuation correction technique for single-photon
      emission computed tomography partial angle acquisition of Jaszczak phantom.
AB  - The acquisition and processing of the Jaszczak phantom is a recommended test by
      the American College of Radiology for evaluation of gamma camera system
      performance. To produce the reconstructed phantom image for quality evaluation,
      attenuation correction is applied. The attenuation of counts originating from the
      center of the phantom is greater than that originating from the periphery of the
      phantom causing an artifactual appearance of inhomogeneity in the reconstructed
      image and complicating phantom evaluation. Chang's mathematical formulation is a
      common method of attenuation correction applied on most gamma cameras that do not
      require an external transmission source such as computed tomography, radionuclide
      sources installed within the gantry of the camera or a flood source. Tomographic
      acquisition can be obtained in two different acquisition modes for dual-detector
      gamma camera; one where the two detectors are at 180 degrees  configuration and
      acquire projection images for a full 360 degrees , and the other where the two
      detectors are positioned at a 90 degrees  configuration and acquire projections
      for only 180 degrees . Though Chang's attenuation correction method has been used
      for 360 degrees  angle acquisition, its applicability for 180 degrees  angle
      acquisition remains a question with one vendor's camera software producing
      artifacts in the images. This work investigates whether Chang's attenuation
      correction technique can be applied to both acquisition modes by the development
      of a Chang's formulation-based algorithm that is applicable to both modes.
      Assessment of attenuation correction performance by phantom uniformity analysis
      illustrates improved uniformity with the proposed algorithm (22.6%) compared to
      the camera software (57.6%). 

PMID- 27051168
TI  - Analyzing the characteristics of 6 MV photon beam at low monitor unit settings.
AB  - Analyzing the characteristics of a low monitor unit (MU) setting is essential,
      particularly for intensity-modulated techniques. Intensity modulation can be
      achieved through intensity-modulated radiotherapy (IMRT) or volumetric-modulated
      arc therapy (VMAT). There is possibility for low MUs in the segments of IMRT and
      VMAT plans. The minimum MU/segment must be set by the physicist in the treatment
      planning system at the time of commissioning. In this study, the characteristics
      such as dose linearity, stability, flatness, and symmetry of 6 MV photon beam of
      a Synergy linear accelerator at low MU settings were investigated for different
      dose rates. The measurements were performed for Synergy linear accelerator using
      a slab phantom with a FC65-G chamber and Profiler 2. The MU linearity was studied
      for 1-100 MU using a field size of 10 cm *10 cm. The linearity error for 1 MU was
      4.2%. Flatness of the beam was deteriorated in 1 MU condition. The beam stability
      and symmetry was well within the specification. Using this study, we conclude
      that the treatment delivered with <3 MU may result in uncertainty in dose
      delivery. To ensure the correct dose delivery with less uncertainty, it is
      recommended to use >=3 MU as the minimum MU per segment in IMRT and VMAT plans. 

PMID- 27051169
TI  - Evaluation of various boluses in dose distribution for electron therapy of the
      chest wall with an inward defect.
AB  - Delivering radiotherapy to the postmastectomy chest wall can be achieved using
      matched electron fields. Surgical defects of the chest wall change the dose
      distribution of electrons. In this study, the improvement of dose homogeneity
      using simple, nonconformal techniques of thermoplastic bolus application on a
      defect is evaluated. The proposed phantom design improves the capability of film
      dosimetry for obtaining dose profiles of a patient's anatomical condition. A
      modeled electron field of a patient with a postmastectomy inward surgical defect
      was planned. High energy electrons were delivered to the phantom in various
      settings, including no bolus, a bolus that filled the inward defect (PB0), a
      uniform thickness bolus of 5 mm (PB1), and two 5 mm boluses (PB2). A reduction of
      mean doses at the base of the defect was observed by any bolus application. PB0
      increased the dose at central parts of the defect, reduced hot areas at the base
      of steep edges, and reduced dose to the lung and heart. Thermoplastic boluses
      that compensate a defect (PB0) increased the homogeneity of dose in a fixed depth
      from the surface; adversely, PB2 increased the dose heterogeneity. This study
      shows that it is practical to investigate dose homogeneity profiles inside a
      target volume for various techniques of electron therapy. 

PMID- 27051170
TI  - Comparison of computed tomography dose index in polymethyl methacrylate and nylon
      dosimetry phantoms.
AB  - The use of computed tomography (CT) scanning has been growing steadily.
      Therefore, CT dose measurement is becoming increasingly important for patient
      protection and optimization. A phantom is an important tool for dose measurement.
      This paper focuses on the evaluation of a CT dosimetry phantom made from nylon,
      instead of the standard polymethyl methacrylate (PMMA), which is not readily
      available or is too expensive in some countries. Comparison between phantoms made
      from the two materials is made in terms of measurements of the CT dose indices
      (CTDI). These were measured for four different beam widths and kVp settings at
      the center and periphery in head and body phantoms made from both materials and
      weighted CTDIs (CTDIw) were calculated. CT numbers along the z-axis of the
      phantom were also measured at the center and four peripheral positions of each
      scanned slice to check phantom homogeneity. Results showed that values for the
      CTDIw measured in the nylon phantoms were slightly higher than those from the
      PMMA while CT numbers for nylon were lower than those of PMMA. This is because
      the mass attenuation coefficient of the nylon is higher. Nylon could be used as a
      substitute material for CT dosimetry phantom to enable measurements and
      adjustment factors are given which could be used to estimate PMMA values for
      making comparisons with displayed values. 

PMID- 27051171
TI  - The modulating effect of royal jelly consumption against radiation-induced
      apoptosis in human peripheral blood leukocytes.
AB  - The present work was designed to assess the radioprotective effect of royal jelly
      (RJ) against radiation-induced apoptosis in human peripheral blood leukocytes. In
      this study, peripheral blood samples were obtained on days 0, 4, 7, and 14 of the
      study from six healthy male volunteers taking a 1000 mg RJ capsule orally per day
      for 14 consecutive days. On each sampling day, all collected whole blood samples
      were divided into control and irradiated groups which were then exposed to the
      selected dose of 4 Gy X-ray. Percentage of apoptotic cells (Ap %) was evaluated
      for all samples immediately after irradiation (Ap0) and also after a 24 h
      postirradiation incubation at 37 degrees C in 5% CO2 (Ap24) by the use of neutral
      comet assay. Concerning Ap0, collected data demonstrated that the percentage of
      apoptotic cells in both control and irradiated groups did not significantly
      change during the study period. However, with respect to Ap24, the percentage of
      apoptotic cells in irradiated groups gradually reduced during the experiment,
      according to which a significant decrease was found after 14 days RJ consumption
      (P = 0.002). In conclusion, the present study revealed the protective role of 14
      days RJ consumption against radiation-induced apoptosis in human peripheral blood
      leukocytes. 

PMID- 27051172
TI  - Comparison of two programs in calculating electron output factors at extended
      source-surface distances.
AB  - Monitor units (MUs) calculated by radiotherapy treatment planning systems need to
      be verified independently. At extended source-surface distances (SSDs), different
      output factors (OFs) can be given by different independent MU checking packages
      due to the calculation methods used and assumptions made within them. The
      accuracy of two software packages - RadCalc((r)) (LifeLine Software Inc., Austin,
      USA) and eDatabook (Y. Wang, Radiation Oncology Institute, Sydney, AUS) - was
      determined by comparing the calculated OFs directly to measured OFs for a series
      of standard electron cutouts on an Elekta Synergy linear accelerator at standard
      and extended SSDs (100 cm and above). For the majority of the measurements made,
      eDatabook provided OFs closer to the measured value than RadCalc; however, in two
      cases, eDatabook was unable to provide a factor. RadCalc failed to calculate the
      OFs accurately at extended SSDs as its calculation is based on the assumption
      that the established effective-SSD curve can accurately predict the data where
      there are no measurements available. The accuracy of eDatabook is due to its use
      of a linear interpolation to determine the OF at an extended SSD when there are
      no measurement data available. 

PMID- 27051173
TI  - Respiratory gated radiotherapy-pretreatment patient specific quality assurance.
AB  - Organ motions during inter-fraction and intra-fraction radiotherapy introduce
      errors in dose delivery, irradiating excess of normal tissue, and missing target
      volume. Lung and heart involuntary motions cause above inaccuracies and gated
      dose delivery try to overcome above effects. Present work attempts a novel method
      to verify dynamic dose delivery using a four-dimensional (4D) phantom. Three
      patients with mobile target are coached to maintain regular and reproducible
      breathing pattern. Appropriate intensity projection image set generated from 4D
      computed tomography (4D-CT) is used for target delineation. Intensity modulated
      radiotherapy plans were generated on selected phase using CT simulator (Siemens
      AG, Germany) in conjunction with "Real-time position management" (Varian, USA) to
      acquire 4D-CT images. Verification plans were generated for both ion chamber and
      Gafchromic (EBT) film image sets. Gated verification plans were delivered on the
      phantom moving with patient respiratory pattern. We developed a MATLAB-based
      software to generate maximum intensity projection, minimum intensity projections,
      and average intensity projections, also a program to convert patient breathing
      pattern to phantom compatible format. Dynamic thorax quality assurance (QA)
      phantom (Computerized Imaging Reference Systems type) is used to perform the
      patient specific QA, which holds an ion chamber and film to measure delivered
      radiation intensity. Exposed EBT films are analyzed and compared with treatment
      planning system calculated dose. The ion chamber measured dose shows good
      agreement with planned dose within +/- 0.5% (0.203 +/- 0.57%). Gamma value
      evaluated from EBT film shows passing rates 92-99% (96.63 +/- 3.84%) for 3% dose
      and 3 mm distance criteria. Respiratory gated treatment delivery accuracy is
      found to be within clinically acceptable level. 

PMID- 27051174
TI  - In regard to "Setup error analysis in helical tomotherapy based image-guided
      radiation therapy treatments".

PMID- 27051175
TI  - Reply to the comments on "Setup error analysis in helical tomotherapy based image
      guided radiation therapy treatments" by Slav Yartsev.

PMID- 27051176
TI  - Seroepidemiology of bluetongue in South Bengal.
AB  - AIM: With the aim of revealing the epidemiological intricacies of bluetongue (BT)
      in the southern part of West Bengal state, the present study was undertaken to
      assess seroprevalence of BT along with identification of the vector of the
      disease, i.e., Culicoides midges available in the region in their breeding season
      with conducive environmental factors, if any. MATERIALS AND METHODS: A total of
      1509 (sheep-504, goat-1005) samples were collected from three different
      agroclimatic zones of South Bengal viz. new alluvial, red laterite and coastal
      saline. To detect anti-BT antibodies in the collected serum samples, indirect
      enzyme-linked immunosorbent assay (i-ELISA) was performed. Culicoides midges were
      collected from those agro-climatic zones of South Bengal for species
      identification. The meteorological parameters, viz. temperature (maximum and
      minimum), rainfall and relative humidity of three agro-climatic zones of South
      Bengal were analyzed for the months of July to December during 2010-2013.
      RESULTS: The overall seropositivity was 33.13% and 30.24% in sheep and goat,
      respectively as assessed by i-ELISA. In South Bengal, the predominant species of
      Culicoides found were Culicoides schultzei, Culicoides palpifer and Culicoides
      definitus. CONCLUSION: Since virus transmitting species of Culicoides midges
      could be detected in South Bengal, besides high seropositivity in ruminants, the
      possibility of circulating BT virus in South Bengal is quite imminent.

PMID- 27051177
TI  - Incidence of Aeromonas spp. infection in fish and chicken meat and its related
      public health hazards: A review.
AB  - Aeromonas is recognized to cause a variety of diseases in man. In humans, they
      are associated with intestinal and extra-intestinal infections. With the growing
      importance of Aeromonas as an emerging pathogen, it is important to combat this
      organism. It is indisputable that Aeromonas strains may produce many different
      putative virulence factors such as enterotoxins, hemolysins or cytotoxins, and
      antibiotic resistance against different antibiotics. The ability of these
      bacteria to grow competitively at 5 degrees C may be indicative of their
      potential as a public health hazard. Comprehensive enteric disease surveillance
      strategies, prevention and education are essential for meeting the challenges in
      the years ahead. It is important for us to promote the value of enteric cultures
      when patients have a gastrointestinal illness or bloody diarrhea or when multiple
      cases of enteric disease occur after a common exposure. With the growing
      importance of Aeromonas as an emerging pathogen, it is important to combat this
      organism. It is indisputable that Aeromonas strains may produce many different
      putative virulence factors, such as enterotoxins, hemolysins or cytotoxins. It
      has been established that aerolysin is a virulence factor contributing to the
      pathogenesis of Aeromonas hydrophila infection. Fish and chicken play an
      important role in the transmission of this pathogen to humans. In the present
      study, the high prevalence of toxin-producing strains was found among the
      Aeromonas isolates. The ability of these bacteria to grow competitively at 5
      degrees C may be indicative of their potential as a public health hazard. The
      present review was constructed with a view to highlight the zoonotic importance
      of Aeromonas pathogen in fish and chicken meat. 

PMID- 27051178
TI  - Intrigues of biofilm: A perspective in veterinary medicine.
AB  - Biofilm has a tremendous impact in the field of veterinary medicine, especially
      the livestock industry, leading to a serious economic loss. Over the years,
      little attention has been given to biofilm in animals with most of the research
      geared toward human biofilm diseases. The greatest challenge posed by biofilm is
      in its incredible ability to resist most of the currently existing antibiotics.
      This mystery can best be demystified through understanding the mechanism of the
      quorum sensing which regulate the pathophysiology of biofilm. Ability of biofilm
      formation in a variety of inanimate surfaces such as animal food contact surfaces
      is responsible for a host of biofilm diseases affecting animals and humans. In
      this review, we highlighted some of the challenges of biofilm in livestock and
      food industries. Also highlighted are; mechanisms of biofilm development, best
      diagnostic approach and possible novel therapeutic measures needed to combat the
      menace of biofilm in veterinary medicine. 

PMID- 27051179
TI  - Hematobiochemical profile in Surti goats during post-partum period.
AB  - AIM: The study was undertaken to find out the changes in hematobiochemical
      profile in post-partum Surti goats. MATERIALS AND METHODS: The present study was
      conducted on 40 Surti goats out of which 20 goats who had undergone recent
      parturition acted as treatment group and 20 non-pregnant animals comprised
      control group. Blood samples were collected from the treatment group on 0, 7, 14,
      21, 30, and 45 days post kidding and once from the control group. Blood samples
      were analyzed for hematological parameters such as hemoglobin (Hb), packed cell
      volume (PCV), total erythrocyte count (TEC), total leukocyte count (TLC),
      differential leukocyte count, and biochemical metabolites such as total protein
      (TP), albumin, globulin, total cholesterol (TC), triglycerides (TG), non
      esterified fatty acid (NEFA), glucose, and urea. RESULTS: Hb level was the
      highest on the 45(th) day and lowest on the day of parturition. Significantly low
      level of Hb, PCV, and lymphocyte was found on 0 day and significantly high level
      was found on the 45(th) day. TEC was also low on the 0 day and high on the 45(th)
      day post kidding, but the difference was non-significant. Mid-sized cells and
      granulocyte percentage decreased significantly from 0 to 45(th) day post-partum.
      TP, albumin, and urea were found to be lowest on 0 day and highest on 45(th) day
      post-partum. Urea concentration increased parallel to TP indicating an increase
      in urea production with catabolism of protein. The globulin concentration also
      increased from 0 to 45(th) day post-partum, but the difference was non
      significant. TC, TG, and NEFA were the highest on 0 day and lowest on the 45(th)
      day post-partum. Decrease in TC and TG from 0 to 45(th) day post-partum indicates
      that the animals utilized the lipids for the supply of energy for milk
      production. High level of NEFA acts as an indicator of negative energy status but
      in the present study, the high glucose level on 0 day indicates that the animals
      were in positive energy status. The glucose concentration decreased up to 14(th)
      day post-partum and then started increasing from 21(st) day onward. CONCLUSION:
      Hematobiochemical parameters are indicative of health status of animals.
      Significantly low values of Hb, PCV, and TLC during first 2 weeks post-partum are
      indicative of stress. Catabolism of protein occurred during 2 weeks post-partum,
      as observed from increase in urea concentration. Decrease TGs and high level of
      NEFA during the transition period are suggestive of utilization of lipids for the
      supply of energy. High glucose level on 0 day indicates that the animals were in
      positive energy status.

PMID- 27051180
TI  - Analysis of viral protein-2 encoding gene of avian encephalomyelitis virus from
      field specimens in Central Java region, Indonesia.
AB  - AIM: Avian encephalomyelitis (AE) is a viral disease which can infect various
      types of poultry, especially chicken. In Indonesia, the incidence of AE infection
      in chicken has been reported since 2009, the AE incidence tends to increase from
      year to year. The objective of this study was to analyze viral protein 2 (VP-2)
      encoding gene of AE virus (AEV) from various species of birds in field specimen
      by reverse transcription polymerase chain reaction (RT-PCR) amplification using
      specific nucleotides primer for confirmation of AE diagnosis. MATERIALS AND
      METHODS: A total of 13 AEV samples are isolated from various species of poultry
      which are serologically diagnosed infected by AEV from some areas in central
      Java, Indonesia. Research stage consists of virus samples collection from field
      specimens, extraction of AEV RNA, amplification of VP-2 protein encoding gene by
      RT-PCR, separation of RT-PCR product by agarose gel electrophoresis, DNA
      sequencing and data analysis. RESULTS: Amplification products of the VP-2
      encoding gene of AEV by RT-PCR methods of various types of poultry from field
      specimens showed a positive results on sample code 499/4/12 which generated DNA
      fragment in the size of 619 bp. Sensitivity test of RT-PCR amplification showed
      that the minimum concentration of RNA template is 127.75 ng/ul. The multiple
      alignments of DNA sequencing product indicated that positive sample with code
      499/4/12 has 92% nucleotide homology compared with AEV with accession number
      AV1775/07 and 85% nucleotide homology with accession number ZCHP2/0912695 from
      Genbank database. Analysis of VP-2 gene sequence showed that it found 46
      nucleotides difference between isolate 499/4/12 compared with accession number
      AV1775/07 and 93 nucleotides different with accession number ZCHP2/0912695.
      CONCLUSIONS: Analyses of the VP-2 encoding gene of AEV with RT-PCR method from 13
      samples from field specimen generated the DNA fragment in the size of 619 bp from
      one sample with sample code 499/4/12. The sensitivity rate of RT-PCR is to
      amplify the VP-2 gene of AEV until 127.75 ng/ul of RNA template. Compared to
      Genbank databases, isolate 499/4/12 has 85% and 92% nucleotide homology.

PMID- 27051181
TI  - Effect of different culture systems on the production of foot and mouth disease
      trivalent vaccine.
AB  - AIM: This study aims to determine the effect of the stationary rawx, roller, and
      the suspension cell culture systems on the total virus yield infectivity and
      antigenicity. MATERIALS AND METHODS: Three serotypes of foot and mouth disease
      virus (FMDV) (serotype A, O and SAT-2) were inoculated separately into baby
      hamster kidney-21 cell line in rawx, roller, and suspension cultivation systems
      using multiplicity of infection (1:100). Samples were taken from the total virus
      yield from each system at 15, 18, 21, and 24 h post-inoculation. Testing the
      total virus yield infectivity through virus titration and antigenicity through
      estimation of complement fixing titer and 146S content and evaluation of the
      potency of the vaccine prepared from the different cultivation systems were done.
      RESULTS: The results showed that the FMDV titer of serotype A, O, and SAT-2
      obtained from the roller cultivation system showed the highest level followed by
      suspension cultivation system then the rawx cultivation system. The FMDV titer
      showed its highest level at 21 h post-inoculation in all the cultivation systems
      and then decline at 24 h post-inoculation. The antigenicity reached its highest
      value content at 18 h post-inoculation either by complement fixation test or by
      quantifying the 146S intact virion. Montanide ISA 206 oil inactivated trivalent
      vaccines were prepared from the tested serotypes (A Iran O5. O Panasia and SAT
      2/EGY/2012) harvested at 18 h post-inoculation from the 3 culture systems. The
      results of tracing the antibody response showed that the mean antibody response
      from the roller cultivation system start its protective antibody titer earlier at
      2 weeks post-vaccination (WPV) than the vaccine prepared from the other two
      cultivation system and the immune protection period lasts longer for 36 WPV for
      the roller cultivation system vaccine than the other two cultivation systems.
      CONCLUSION: The best cultivation system used for the production of FMD vaccine
      regarding its highest infectivity and antigenicity is the roller system.

PMID- 27051182
TI  - Effect of age, sex and physiological stages on hematological indices of Banni
      buffalo (Bubalus bubalis).
AB  - AIM: To determine the physiological baseline values for hematological indices of
      Banni buffalo (Bubalus bubalis) as well as to assess their alteration due to age,
      sex and physiological stages. MATERIALS AND METHODS: A total of 42 clinically
      healthy Banni buffaloes were categorized into seven groups (n=6): Group I (male
      calves <=1 year), Group II (bulls >1 year), Group III (female calves <=1 year),
      Group IV (pregnant lactating buffaloes), Group V (non-pregnant lactating
      buffaloes), Group VI (pregnant dry buffaloes), and Group VII (non-pregnant dry
      buffaloes). Blood samples collected aseptically from all the experimental groups
      were analyzed employing automated hematology analyzer. The data obtained were
      statistically analyzed; the mean and standard deviations were calculated and set
      as the reference values. RESULTS: The erythrocytic indices viz. total
      erythrocytes count (TEC), hemoglobin, and packed cell volume (PCV) were
      significantly higher in bulls as compared to that of male calves unlike mean
      corpuscular volume, mean corpuscular hemoglobin (MCH), and MCH concentration. The
      female calves had higher TEC and PCV than the adult buffaloes irrespective of
      sex. The total leukocyte count (TLC) and neutrophil counts in male calves were
      significantly lower than the bulls unlike the eosinophil, while monocyte and
      basophil remained unchanged with age. The TLC, differential leukocyte count and
      platelet count varied non-significantly among the adult female groups at
      different physiological stages. However, neutrophils were found to be apparently
      higher in lactating buffaloes. CONCLUSION: The present study would be helpful for
      physiological characterization of this unique buffalo breed of Gujarat. Further,
      data generated may be a tool for monitoring the health and prognosis as well as
      diagnosis of diseases.

PMID- 27051183
TI  - Retrospective analyses of dogs found serologically positive for Ehrlichia canis
      in Cebu, Philippines from 2003 to 2014.
AB  - AIM: The study aimed to document the clinical and hematological observations of
      dogs found serologically positive for Ehrlichia canis and to identify parameters
      or factors that are associated with the disease with focus on the anemic and
      thrombocytopenic state of the infected dogs. MATERIALS AND METHODS: From 7
      participating veterinary establishments, a total of 913 cases from 2003 to 2014
      were initially assessed using inclusion criteria, including E. canis diagnosis by
      the attending veterinarian and the presence of ticks or history of infestation,
      thrombocytopenia, and/or anemia. From these, 438 cases that were found
      serologically positive for E. canis using commercial test kits were selected.
      Profile, clinical observations and hematological test results were obtained from
      the selected cases. Computations for statistical associations between the anemic
      and thrombocytopenic state of the infected dogs and their profile, observed
      clinical signs and other hematological values were performed. RESULTS: Most of
      the dogs were purebred (60.0%) and female (51.1%) and were within the age range
      of 1-5 years (38.4%). The mean packed cell volume (PCV), red blood cell (RBC)
      count, and platelet count were lower than the normal values while the absolute
      count of basophils were higher than normal values. Creatinine and blood urea
      nitrogen (BUN) appear to be elevated. The most common clinical signs observed
      were inappetence (41.3%), lethargy/depression (35.6%), vomiting (32.4%), fever
      (18.5%), paleness (8.2%), and epistaxis (6.6%). Analyses showed that there were
      no significant differences on the hematological values and clinical signs between
      thrombocytopenic and non-thrombocytopenic seropositive dogs. Moreover, very weak
      correlations between platelet count and RBC count, absolute lymphocyte count, and
      neutrophil count were found. On the other hand, only paleness (p=0.008) and
      epistaxis (p=0.004) were found to be significantly different between anemic and
      non-anemic patients. This coincided with the linear regression results where PCV
      (p=0.000, R=0.787, R(2)=0.619) was moderately correlated with the RBC count. In
      addition, eosinophil count was found weakly correlated. CONCLUSION: E. canis
      infection in dogs may produce varied clinical signs that may be influenced by the
      thrombocytopenic and anemic states of affected animals. Complete blood counts
      remain important in the diagnosis of the disease, especially the platelet and RBC
      counts. Creatinine, BUN and alanine aminotransferase can be of value in the
      diagnosis of the infection. Several cases were lost to follow-up and appeared to
      be a challenge for handling veterinarians to monitor compliance of owners and
      progress of infected patients.

PMID- 27051184
TI  - Epidemiological study of bovine brucellosis in three senatorial zones of Bauchi
      State, Nigeria.
AB  - AIM: To determine the seroepidemiological patterns of bovine brucellosis in three
      senatorial zones of Bauchi State, Nigeria. MATERIALS AND METHODS: Blood samples
      were aseptically collected from the anterior jugular vein of 336 slaughtered
      cattle, between September 2013 and March 2014 in three senatorial zones of Bauchi
      State, Nigeria. The sera obtained were screened for brucellosis using rose Bengal
      plate test (RBPT) and serum agglutination test (SAT) in parallel. The data
      generated was subjected to Chi-square and Fishers exact test analysis to
      establish whether there is a relationship between the breeds, sex, and location
      of the animals sampled. RESULTS: Of the 336 cattle screened, 18 (5.4%) and 13
      (3.9%) were positive by RBPT and SAT, respectively. There was no statistically
      significant association (p>0.05) between the sex, age, and location of cattle
      with seropositivity of brucellosis in the state. It was concluded that
      brucellosis is prevalent in Bauchi State. Further study is recommended in other
      abattoirs and herds of cattle in Bauchi State for confirmation of the status of
      the disease among cattle slaughtered in the state. CONCLUSION: A high
      seroprevalence of brucellosis among the cattle in Bauchi state indicates that the
      disease is endemic and cattle are one of the animals that perpetuate and sustain
      the disease.

PMID- 27051185
TI  - Genetic structure of Mugil cephalus L. populations from the northern coast of
      Egypt.
AB  - AIM: The gray mullet, Mugil cephalus, has been farmed in semi-intensive ponds
      with tilapia and carps in Egypt for years. The current study used the fluorescent
      amplified fragment length polymorphism (F-AFLP) technique to search for genetic
      differences between the populations of M. cephalus in the northern region of
      Egypt and to detect the gene flow between sampled locations and the homogeneity
      within M. cephalus genetic pool in Egypt. MATERIALS AND METHODS: To fulfill the
      study objectives 60 (15/location) samples were collected from four northern coast
      governorates of Egypt (Alexandria "sea," Kafr El-Sheikh "farm," Damietta "farm"
      and Port Said "sea"). Three replicates of bulked DNA (5 samples/replicate) for
      each location were successfully amplified using the standard AFLP protocol using
      fluorescent primers. DNA polymorphism, genetic diversity, and population
      structure were assessed while positive outlier loci were successfully detected
      among the sampled locations. Based on the geographical distribution of sampling
      sites, the gene flow, the genetic differentiation, and correlations to sampling
      locations were estimated. RESULTS: A total of 1890 polymorphic bands were scored
      for all locations, where 765, 1054, 673, and 751 polymorphic bands were scored
      between samples from Alexandria, Kafr El-Sheikh, Damietta and Port Said,
      respectively. The effective number of alleles (ne) for all bulked samples
      combined together was 1.42. The expected heterozygosity under Hardy-Weinberg
      assumption (He) for all bulked samples combined together was 0.28. Bulked samples
      from Damietta yielded the lowest ne (1.35) and the lowest He (0.23) when
      inbreeding coefficient (FIS) = 1. Bulked samples from Kafr El-Sheikh scored the
      highest ne (1.55) and the highest He (0.37). Bulked samples from Alexandria
      scored 1.40 for ne and 0.26 for He, while bulked samples from Port Said scored
      1.39 for ne and 0.26 for He. The observed bulked samples formed three sub
      population groups, where none is limited to a certain sampling location. A high
      differentiation among locations was detected, however, is not fully isolating the
      locations. Gene flow was 0.58. Positive outliers loci (117) were detected among
      the four sampled locations while weak significant correlation (r=0.15, p=0.03)
      was found for the distance between them. CONCLUSION: Even though this species is
      cultivated in Egypt, the wild population is still present and by the current
      study a flow of its genes is still exchanged through the northern coast of Egypt.
      Which contribute to the cultivated populations leading to heterogeneity in its
      genetic pool and consequently affects the production consistency of M. cephalus
      in Egypt.

PMID- 27051186
TI  - Detection of Clostridium perfringens alpha toxin gene in lambs by loop mediated
      isothermal amplification.
AB  - AIM: The loop mediated isothermal amplification (LAMP) was standardized for rapid
      detection of Clostridium perfringens. MATERIALS AND METHODS: A total of 120 fecal
      samples were collected from enterotoxemia suspected lambs were used for screening
      of C. perfringens cpa gene by LAMP. The specificity of the LAMP amplified
      products was tested by digesting with restriction enzyme XmnI for alpha toxin
      gene. RESULTS: Out of 120 samples screened 112 (93.3%) samples were positive by
      both LAMP and polymerase chain reaction (PCR) for detection of cpa gene which
      indicated the equal sensitivity of both the tests. The enzyme produced single cut
      in 162 base pair amplified product of alpha toxin gene at 81 base pair resulting
      in a single band in gel electrophoresis. CONCLUSION: Both LAMP and PCR for
      detection of cpa gene indicated the equal sensitivity of both the tests.
      Standardization of LAMP reaction for amplification of epsilon and beta toxin
      genes will help to identify the C. perfringens toxin types from the clinical
      samples. The test could be a suitable alternative to the PCR in detection of
      toxin types without the help of sophisticated machinery like thermal cycler.
      Considering its simplicity in operation and high sensitivity, there is the
      potential use of this technique in clinical diagnosis and surveillance of
      infectious diseases.

PMID- 27051187
TI  - Prevalence and characterization of multi-drug resistant Salmonella Enterica
      serovar Gallinarum biovar Pullorum and Gallinarum from chicken.
AB  - AIM: Salmonella is an important zoonotic pathogen responsible for animal and
      human diseases. The aim of the present study was to determine the prevalence and
      stereotyping of Salmonella isolates isolated from apparently healthy poultry.
      Furthermore, the clonal relatedness among the isolated Salmonella serovars was
      assessed. MATERIALS AND METHODS: A total of 150 cloacal swab samples from
      apparently healthy chickens were collected, and were subjected for the isolation
      and identification of associated Salmonella organisms. The isolated colonies were
      identified and characterized on the basis of morphology, cultural characters,
      biochemical tests, slide agglutination test, polymerase chain reaction, and
      pulsed-field gel electrophoresis (PFGE). Antibiotic sensitivity patterns were
      also investigated using commonly used antibiotics. RESULTS: Of the 150 samples,
      11 (7.33%) produced characteristics pink colony with black center on XLD agar
      medium, and all were culturally and biochemically confirmed to be Salmonella. All
      possessed serovar-specific gene SpeF and reacted uniformly with group D antisera,
      suggesting that all of the isolates were Salmonella Enterica serovar Gallinarum,
      biovar Pullorum and/or Gallinarum. Antimicrobial susceptibility testing revealed
      that 54.54% of the isolated Salmonella Enterica serovars were highly sensitive to
      ciprofloxacin, whereas the 81.81% isolates were resistant to amoxycillin,
      doxycycline, kanamycin, gentamycin, and tetracycline. Pulsed-field gel
      electrophoresis of the XbaI-digested genomic DNA exhibited identical banding
      patterns, suggesting that the multidrug resistant Salmonella Enterica serovars
      occurring in commercial layers are highly clonal in Bangladesh. CONCLUSION: The
      present study was conducted to find out the prevalence of poultry Salmonella in
      layer chicken and to find out the clonal relationship among them. The data in
      this study suggest the prevalence of Salmonella Enterica, which is multidrug
      resistant and highly clonal for commercial layers of Bangladesh.

PMID- 27051188
TI  - Prevalence of vero toxic Escherichia coli in fecal samples of domestic as well as
      wild ruminants in Mathura districts and Kanpur zoo.
AB  - AIM: The present study was planned to reveal the prevalence of verocytotoxigenic
      Escherichia coli (VTEC) in fecal samples of domestic and wild ruminants in
      Mathura district and Kanpur zoo. MATERIALS AND METHODS: A total of 240 fecal
      samples comprising 60 each of cattle, buffalo, sheep and deer from Mathura
      districts and Kanpur zoo were screened for the presence of E. coli and VTEC genes
      positive by polymerase chain reaction (PCR). RESULT: Out of 240 fecal samples,
      212 E. coli strains were obtained. All the E. coli isolates were screened by PCR
      to detect virulence genes stx1 , stx2 , eaeA and hlyA. Of these, 25 isolates were
      identified as VTEC. The prevalence of VTEC in cattle, buffalo, sheep and deer was
      found 13.4% (8/60), 13.4% (8/60), 6.67% (4/60) and 8.33% (5/60), respectively.
      CONCLUSION: stx1 , stx2 , eaeA and hlyA genes were prevalent in VTEC isolates
      from feces of cattle, buffalo, sheep and deer population of Mathura districts and
      Kanpur zoo. The presence of VTEC isolates in this region may pose a threat to
      public health.

PMID- 27051189
TI  - Episodes of clinical mastitis and its relationship with duration of treatment and
      seasonality in crossbred cows maintained in organized dairy farm.
AB  - AIM: Present study aimed to evaluate the different episodes of clinical mastitis
      (CM) and influence of duration of treatment and seasonality on the occurrence of
      different episodes of CM in crossbred cows. MATERIALS AND METHODS: A total of
      1194 lactation data of crossbred CM cows were collected from mastitis treatment
      record from 2002 to 2012. Data of CM cows were classified into types of episodes
      (pattern of repeated or multiple episodes occurrence) and number of episodes
      (magnitude of multiple cases). Types of episodes were divided as single (clinical
      cure by a single episode of treatment), relapse (retreatment of the same cow
      within 21 days), recurrence (new CM at least 21 days after treatment), and both
      (relapse and recurrence). The season was classified as winter (December to
      March), summer (April to June), rainy (July to September), and autumn (October to
      November). The difference between incidences of different types of CM episodes
      and the association between number or type of CM episodes with duration of
      treatment and seasons of CM occurrence were analyzed by Chi-square test. RESULTS:
      Among 1194 animals suffered with CM, 53, 16, and 18% had the single episode,
      relapse, and recurrence, respectively; while 13% suffered by both relapse and
      recurrence. We estimated the duration of treatment and found 80% of the cows
      treated 1-8 days, in which 65% treated for 1-4 days, while 35% cows were treated
      for 5-8 days. Further, 12% cows treated for 9-15 days and 7.5% cows treated >15
      days. The relationship between duration of treatment and different episodes of CM
      revealed that 1-8 days treated cows were mostly cured by the single episode with
      less relapse and recurrence. In contrast, the incidences of recurrence and
      relapse episodes were higher in cows treated for more than 9 days. The highest
      incidence of relapse was noticed in winter (36%) than other seasons (10-28%),
      while the recurrence was less during autumn (9%) compared to other seasons (20
      40%). CONCLUSION: Cows those suffered by both relapse and recurrence were more
      susceptible to CM, and they need to be culled from farm to control the
      transmission of infections. Although the influence of seasonality was difficult
      to understand, the higher magnitude of relapse and recurrence during winter
      suggested the adverse effects of cold stress on treatment outcome.

PMID- 27051192
TI  - Anthelmintic activity of Indigofera tinctoria against gastrointestinal nematodes
      of sheep.
AB  - AIM: Gastrointestinal (GI) nematodes are considered as a major constraint for
      successful sheep production. Control of these parasites heavily relies on the use
      of chemical anthelmintics. Over the past decades, the development of anthelmintic
      resistance to various groups of anthelmintics and problem of drug residues in
      animal products has awakened interest in medicinal plants as an alternative
      source of anthelmintics. Hence, this study was undertaken to evaluate the
      anthelmintic efficacy of Indigofera tinctoria by scientifically validated in
      vitro and in vivo tests approved by the World Association for the Advancement of
      Veterinary Parasitology. MATERIALS AND METHODS: In vitro assays such as egg hatch
      assay for ovicidal and larval migration inhibition and larval development assay
      for larvicidal properties were used to investigate in vitro effect of extracts on
      strongyle egg and larvae, respectively. Fecal egg count reduction test was
      conducted in vivo to evaluate the therapeutic efficacy of the extracts
      administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally
      infected with mixed GI nematodes. RESULTS: Ethanolic extract of I. tinctoria
      demonstrated significant (p<0.01) inhibition on egg hatching at concentrations of
      40 mg/ml and 80 mg/ml. In in vivo assay, the ethanolic extract of I. tinctoria
      reduced the fecal egg count ranging between 30.82% and 47.78% at various doses
      (125, 250 and 500 mg/kg). Although there was a slight variation, all the
      hematological parameters were within the normal range reported for sheep. Except
      for alanine transaminase, the overall mean of all the serum biochemical profile
      was within the normal range for sheep. CONCLUSION: Based on the results obtained
      by in vitro and in vivo assay, the ethanolic extract of I. tinctoria possesses
      anthelmintic activity and could replace the chemical anthelmintics used
      presently.

PMID- 27051191
TI  - Potential of acute phase proteins as predictor of postpartum uterine infections
      during transition period and its regulatory mechanism in dairy cattle.
AB  - Among the various systemic reactions against infection or injury, the acute phase
      response is the cascade of reaction and mostly coordinated by cytokines-mediated
      acute phase proteins (APPs) production. Since APPs are sensitive innate immune
      molecules, they are useful for early detection of inflammation in bovines and
      believed to be better discriminators than routine hematological parameters.
      Therefore, the possibility of using APPs as a diagnostic and prognostic marker of
      inflammation in major bovine health disorders including postpartum uterine
      infection has been explored by many workers. In this review, we discussed
      specifically importance of postpartum uterine infection, the role of energy
      balance in uterine infections and potential of APPs as a predictor of postpartum
      uterine infections during the transition period and its regulatory mechanism in
      dairy cattle. 

PMID- 27051190
TI  - Recent developments in receptor tyrosine kinases targeted anticancer therapy.
AB  - Novel concepts and understanding of receptors lead to discoveries and
      optimization of many small molecules and antibodies as anti-cancerous drugs.
      Receptor tyrosine kinases (RTKs) are such a promising class of receptors under
      the investigation in past three decades. RTKs are one of the essential mediators
      of cell signaling mechanism for various cellular processes. Transformations such
      as overexpression, dysregulation, or mutations of RTKs may result into
      malignancy, and thus are an important target for anticancer therapy. Numerous
      subfamilies of RTKs, such as epidermal growth factor receptor, vascular
      endothelial growth factor receptor, fibroblast growth factor receptors, insulin
      like growth factor receptor, and hepatocyte growth factor receptor, have been
      being investigated in recent years as target for anticancer therapy. The present
      review focuses several small molecules drugs as well as monoclonal antibodies
      targeting aforesaid subfamilies either approved or under investigation to treat
      the various cancers. 

PMID- 27051193
TI  - Comparison of rapid immunodiagnosis assay kit with molecular and
      immunopathological approaches for diagnosis of rabies in cattle.
AB  - AIM: Presently, diagnosis of rabies is primarily based on, conventional
      fluorescent antibody technique (FAT), immunopathological and molecular
      techniques. Recently, rapid immunodiagnostic assay (RIDA) - A monoclonal antibody
      based technique has been introduced for rapid diagnosis of rabies. The present
      investigation is envisaged to study the efficacy of RIDA kit for the diagnosis of
      rabies in cattle. MATERIALS AND METHODS: About 11 brain samples from cattle,
      clinically suspected for rabies, were screened by the FAT, Heminested reverse
      transcriptase polymerase chain reaction (HnRT-PCR), Immunohistochemistry (IHC),
      and RIDA. RESULTS: The sensitivity for detection of rabies from brain tissue by
      RIDA was 85.7% as compared to 100% by IHC as well as HnRT-PCR. The accuracy of
      detection of rabies by RIDA was 91.6% as compared to 100% that of IHC and HnRT
      PCR, whereas specificity of RIDA was 100% like that of the IHC and HnRT-PCR.
      CONCLUSION: Despite a comparatively low-sensitivity and accuracy of RIDA, latter
      can still be useful in screening a large number of field samples promptly.
      However, it is recommended that negative results with RIDA in cattle need to be
      authenticated by suitable alternative diagnostic approaches.

PMID- 27051194
TI  - Effect of heat shock protein 70 polymorphism on thermotolerance in Tharparkar
      cattle.
AB  - AIM: Out of various members of heat shock protein (HSP) superfamily which act a
      molecular chaperon by binding to the denaturing protein thus stabilizing them and
      preserving their activity, HSP70 are of major importance in thermotolerance
      development. Thus, present investigation aimed at a screening of HSP70 gene for
      polymorphisms and possible differences in thermotolerance in Tharparkar breed of
      cattle. MATERIALS AND METHODS: A 295 bp fragment of HSP70 gene was subjected to
      polymerase chain reaction-single-strand conformation polymorphism (SSCP) followed
      by sequencing of different SSCP patterns in 64 Tharparkar cattle. A comparative
      thermotolerance of identified genotypes was analyzed using heat tolerance
      coefficients (HTCs) of animals for different seasons. RESULTS: Three SSCP
      patterns and consequently two alleles namely A and B were documented in one
      fragment of HSP70 gene. On sequencing, one single-nucleotide polymorphism with G
      > T substitution was found at a position that led to a change of amino acid
      aspartate to tyrosine in allele A. It was found that in maintaining near normal
      average rectal temperature, genotype AA was superior (p<=0.01). Genotype AA,
      thus, was found to be most thermotolerant genotype with the highest HTC
      (p<=0.01). CONCLUSION: The polymorphism at HSP70 is expected to be a potent
      determinant for heat tolerance in cattle, which may aid in selection for
      thermotolerance in cattle.

PMID- 27051195
TI  - Hypoglycemic, hypolipidemic and antioxidant effects of pioglitazone, insulin and
      synbiotic in diabetic rats.
AB  - AIM: The objective of the study was to assess the effect of combination treatment
      of insulin, pioglitazone and synbiotic on streptozotocin (STZ)-induced diabetic
      rats. MATERIALS AND METHODS: Diabetes mellitus was induced chemically by
      intraperitoneal administration of STZ (40 mg/kg b.wt) to male Sprague-Dawley
      rats. The rats were divided randomly into six groups of six rats in each. Group 1
      was maintained as a normal control. Group 2 was maintained as diabetic control;
      Group 3 was treated with insulin; Group 4 with insulin + synbiotic; Group 5 with
      insulin + pioglitazone; and Group 6 with insulin + synbiotic + pioglitazone. All
      the animals were treated for 60 days. RESULTS: Body weights, and concentration of
      reduced glutathione (GSH), and high-density lipoproteins cholesterol were
      significantly (p<0.05) reduced, whereas the concentration of blood glucose, total
      cholesterol, triglycerides, protein carbonyls and thiobarbituric acid reacting
      substances, and the activity of GSH peroxidase were significantly (p<0.05)
      elevated in Group 2 at the end of 8(th) week as compared to Group 1. The
      treatment Groups 3, 4, 5 and 6 revealed improvement in all the parameters, and
      the highest improvement was observed in combination Group 6. CONCLUSION: From
      this study, it is concluded that combination of insulin, pioglitazone and
      synbiotic is useful in treating diabetes.

PMID- 27051196
TI  - Isolation and characterization of Shiga toxigenic Escherichia coli of animal and
      bird origin by multiplex polymerase chain reaction.
AB  - AIM: The purpose of this study was to determine the virulence genes and serotype
      of Shiga toxin producing Escherichia coli (STEC) strains isolated from animals
      and birds. MATERIALS AND METHODS: A total of 226 different samples viz., fecal,
      intestinal content, rectal swab and heart blood were collected from different
      clinically affected/healthy animals and birds and were streaked on McConkeys'
      lactose agar and eosin methylene blue agar for isolation of E. coli, confirmed by
      staining characteristics and biochemical tests. By polymerase chain reaction
      (PCR) all the E. coli isolates were screened for certain virulence genes, viz.,
      Shiga toxin 1 (stx1), stx2 and eae and enterohemolytic (Ehly) phenotype was
      observed in washed sheep blood agar plate. All the isolated E. coli strains were
      forwarded to the National Salmonella and Escherichia Centre, Central Research
      Institute, Kasauli (Himachal Pradesh) for serotyping. RESULTS: Out of 226 samples
      138 yielded E. coli. All the isolates were screened for molecular detection of
      different virulent genes, viz. stx1, stx2 and eae, based on which 36 (26.08%)
      were identified as STEC. Among those STEC isolates, 15 (41.67%), 14 (38.89%), 1
      (2.78%) exhibited eae, stx2, stx1 alone, respectively, whereas 4 (11.11%) and 2
      (5.56%) carried both stx1 and stx2, stx2 and eae, respectively. Among the STEC
      isolates 22 were belonged to 15 different sero-groups, viz., O2, O20, O22, O25,
      O43, O60, O69, O90, O91, O95, O106, O118, O130, O162 and O170 and others were
      untypable. Ehly phenotype was observed in 10 (27.78%) the STEC isolates.
      CONCLUSION: The present study concluded that STEC could be isolated from both
      clinically affected as well as healthy animals and birds. Regular monitoring of
      more samples from animal and bird origin is important to identify natural
      reservoir of STEC to prevent zoonotic infection.

PMID- 27051197
TI  - Genetic analysis of growth traits in Harnali sheep.
AB  - AIM: The present investigation was to study genetic characteristics of Harnali
      sheep with respect to growth performance and to estimate genetic parameters.
      MATERIALS AND METHODS: The 22 years (1992-2013) data of growth traits of a 1603
      synthetic population of Harnali sheep maintained at Lala Lajpat Rai University of
      Veterinary and Animal Sciences, Hisar, was utilized for this study. A mixed
      methodology with regression on their dam's weight was used to study the effect of
      non-genetic factors on growth traits. Heritability, genetic and phenotypic
      correlations were estimated using paternal half-sib analysis for body weight at
      various ages and average daily gain (ADG) for different growth periods. RESULT:
      The overall least squares mean of body weights recorded for birth weight (BW),
      weaning weight (WW), six months body weight (SMW), one yearling body weight
      (YBW), average daily gain from birth to 3 months (ADG1) and average daily gain
      from 3 to 12 months (ADG2) were 3.35+/-0.05 kg, 12.41+/-0.08 kg, 16.30+/-0.12 kg,
      21.88+/-0.08 kg, 100.66+/-0.86 g/day and 35.07+/-0.39 g/day, respectively. The
      effects of year of birth significantly (p<0.01) influenced the BW, WW, SMW, YWB,
      ADG1 and ADG2. The effects of sex of lamb significantly (p<0.01) influenced the
      BW, WW SMW, YWB, ADG1 and ADG2. The effects of dam's weight at lambing
      significantly (p<0.01) influenced BW, WW, SMW, YWB, ADG1 and ADG2. No definite
      trend was observed over the years for the averages of body weight and gain. The
      heritability estimates of BW, WW, SMW, YBW, ADG1 and ADG2 were 0.40+/-0.05,
      0.38+/-0.05, 0.45+/-0.06, 0.29+/-0.05, 0.40+/-0.06 and 0.33+/-0.02, respectively.
      The male lambs were significantly heavier than females at all stages of growth.
      The heritability estimates were moderate for all the growth traits and high
      genetic correlations of BW and WW with SMW were found. CONCLUSION: Due to high
      heritability and positive correlations of SMW with other body weights and daily
      gain, it was concluded that selection on the basis of SMW would be the best
      approach to improve growth performance in Harnali sheep.

PMID- 27051198
TI  - Developmental neurotoxicity of monocrotophos and lead is linked to thyroid
      disruption.
AB  - AIM: A role of thyroid disruption in developmental neurotoxicity of monocrotophos
      (MCP) and lead is studied. MATERIALS AND METHODS: A total of 24 female rats after
      conception were randomized into four groups of six each and treated as follows:
      Group I - Sham was administered distilled water orally. Group II - A positive
      control was administered methyl methimazole at 0.02% orally in drinking water.
      Group III - MCP orally at 0.3 mg/kg and Group IV - Lead acetate at 0.2% orally in
      drinking water. The drug was administered from gestation day 3 through post-natal
      day 21 in all the groups. Acetylcholinesterase (AChE) inhibition, thyroid profile
      (thyroid stimulating hormone, T3 and T4), neurodevelopment (brain wet weights,
      DNA, RNA and protein), and neurobehavioral (elevated plus maze, photoactometry,
      and Morris water maze) parameters were assessed in pups. A histopathology of
      thyroid of dams and brain of progeny was conducted. RESULTS: Inhibition of AChE
      was <20%. Thyroid profile decreased in the treatment groups. Neurodevelopmental
      and neurobehavioral parameters did not reveal any significant changes. Thyroid
      architecture was affected significantly with MCP and lead. Cortical layers too
      were affected. The three layers of cerebellum either had abnormal arrangement or
      decreased cellularity in all treated groups relating to thyroid disruption.
      CONCLUSION: MCP and lead might have affected the development of cerebrum and
      cerebellum via thyroid disruption leading to developmental neurotoxicity.

PMID- 27051199
TI  - Loktanella spp. Gb03 as an algicidal bacterium, isolated from the culture of
      Dinoflagellate Gambierdiscus belizeanus.
AB  - AIM: Bacteria associated with harmful algal blooms can play a crucial role in
      regulating algal blooms in the environment. This study aimed at isolating and
      identifying algicidal bacteria in Dinoflagellate culture and to determine the
      optimum growth requirement of the algicidal bacteria, Loktanella sp. Gb-03.
      MATERIALS AND METHODS: The Dinoflagellate culture used in this study was supplied
      by Professor Gires Usup's Laboratory, School of Environmental and Natural
      Resources Sciences, Faculty of Science and Technology, University Kebangsaan
      Malaysia, Malaysia. The culture was used for the isolation of Loktanella sp.,
      using biochemical tests, API 20 ONE kits. The fatty acid content of the isolates
      and the algicidal activity were further evaluated, and the phenotype was
      determined through the phylogenetic tree. RESULTS: Gram-negative, non-motile, non
      spore-forming, short rod-shaped, aerobic bacteria (Gb01, Gb02, Gb03, Gb04, Gb05,
      and Gb06) were isolated from the Dinoflagellate culture. The colonies were pink
      in color, convex with a smooth surface and entire edge. The optimum growth
      temperature for the Loktanella sp. Gb03 isolate was determined to be 30 degrees
      C, in 1% of NaCl and pH7. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that the bacterium belonged to the genus Loktanella of the class
      Alphaproteobacteria and formed a tight cluster with the type strain of Loktanella
      pyoseonensis (97.0% sequence similarity). CONCLUSION: On the basis of phenotypic,
      phylogenetic data and genetic distinctiveness, strain Gb-03, were placed in the
      genus Loktanella as the type strain of species. Moreover, it has algicidal
      activity against seven toxic Dinoflagellate. The algicidal property of the
      isolated Loktanella is vital, especially where biological control is needed to
      mitigate algal bloom or targeted Dinoflagellates.

PMID- 27051200
TI  - Age-specific changes in electrocardiographic parameters in bipolar limb leads of
      conscious female native cats of Odisha.
AB  - AIM: To study and compare the age-specific changes in electrocardiographic (ECG)
      parameters in bipolar limb leads of conscious female native cats of Odisha.
      MATERIALS AND METHODS: 20 healthy female native cats aged between 4 and 36 months
      of age were selected for the study. These queens were divided into two groups of
      10 animals each. Group 1 constituted the queens aged 4-10 months (before puberty)
      with a mean weight of 2.28 kg (+/-0.4 standard error [SE]), and those aged 11-36
      months (after puberty) with a mean weight of 3.72 kg (+/-0.6 SE) were in Group 2.
      The ECG was recorded with a 12-lead standard ECG recorder, Cardiart 108 T-MK VII
      BPL (India) in the Leads I, II, and III. RESULTS: The mean heart rates were
      160.73 (+/-7.83) beats/min and 139.09 (+/-2.72) beats/min in the cats aged 4-10
      months and 11-36 months, respectively. Significant differences existed among Q-
      and R-wave amplitudes and duration of QT-interval in Lead I. In Lead II, duration
      of QT and RR intervals, duration of ST-segment and amplitudes of P- and R-waves
      varied significantly. Significant differences were also observed in the P- and R
      wave amplitudes in Lead III. The mean electrical axis was 63.11 (+/-1.98 degrees
      ) and 50.03 (+/-4.86 degrees ) in the cats aged 4-10 months and 11-36 months,
      respectively. CONCLUSION: Since the ECG studies on conscious cats are scanty, and
      the number of native cats being presented in veterinary hospitals and clinics has
      increased drastically, there is a need to establish the reference values for ECG
      parameters in conscious native cats so that the cardiovascular abnormalities can
      be predicted.

PMID- 27051201
TI  - Effect of incorporation of calcium lactate on physico-chemical, textural, and
      sensory properties of restructured buffalo meat loaves.
AB  - AIM: The present study was conducted to develop a functional meat product by
      fortifying calcium (in the form of calcium lactate) with restructured buffalo
      meat loaf (RBML). MATERIALS AND METHODS: Deboned buffalo meat obtained from the
      carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen
      condition. Calcium fortified RBML were prepared by replacing the lean buffalo
      meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre
      standardized procedure. The developed products were evaluated for physico
      chemical properties, proximate composition, calcium concentration (mg/100 g),
      water activity (aw), Lovibond((r)) tintometer color units, texture profile
      analysis (TPA), and sensory qualities as per-standard procedures. RESULTS: Of the
      various product quality parameters evaluated, cooking yield (%), product pH,
      moisture (%), protein (%), fat (%), and water activity (aw) decreases
      significantly with increasing level of calcium lactate. Calcium content of
      fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to
      6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of
      calcium lactate in treatment products remained comparable among themselves and
      control product, with a gradual decline. CONCLUSIONS: The present study concluded
      that 1.25% calcium lactate was the optimum level for the fortification of calcium
      in RBML without affecting the textural and sensory properties which could meet
      out 15% of recommended dietary allowance for calcium.

PMID- 27051202
TI  - Expression of biologically active bovine interleukin 7 and evaluating the
      activity in vitro.
AB  - AIM: Interleukin 7 (IL-7) is a Upsilonc family cytokine involved in the
      homeostatic proliferation and maintenance of immune cells. In the present study,
      we report the expression of bovine IL-7 (bIL-7) in Escherichia coli and evaluated
      for its biological activity. MATERIALS AND METHODS: The sequence coding for bIL-7
      (mature protein) was amplified from primary bovine kidney cell culture and cloned
      into pET28-a vector and expressed in E. coli (BL 21 DE3). The expressed protein
      was purified by nickel-nitrilotriacetatechromatography, and the reactivity of the
      protein was confirmed by western blotting using monoclonal antibodies raised
      against human IL-7. The biological activity of expressed bIL-7 was evaluated by
      analyzing its effect on the expression of anuclear factor for activated T-cells
      c1 (NFATc1), B-cell lymphoma 2 (Bcl2), suppressor of cytokine signaling 3 (SOCS3)
      molecules in bovine peripheral blood mononuclear cells (PBMCs) by quantitative
      polymerase chain reaction. Ability of the expressed protein was also analyzed by
      its effect on phosphorylating signal transducer and activator 3 (STAT3) molecule
      by immunostaining in human embryonic kidney cells 293 (HEK293) cells. RESULTS:
      The bIL-7 was able to induce the expression of Bcl2 and NFATc1expression in
      bovine PBMCs by 7 and 5-folds, respectively, whereas a 2-fold decrease was
      observed in the case of SOCS3 expression. Immunostaining studies in HEK293 cells
      using antihuman phospho-STAT3 showed activation and nuclear translocation of
      STAT3 molecule on bIL-7 treatment. CONCLUSION: bIL-7 gene was successfully
      amplified, cloned, and expressed in a prokaryotic expression system. The
      biological activity study showed that the E. coli expressed bIL-7 protein is
      biologically active. Considering the role of IL-7 in T-cell homeostasis and
      memory cell generation, this molecule can be used for enhancing the vaccine
      response and that has to be proved by further experiments.

PMID- 27051203
TI  - Utilization of carrageenan, citric acid and cinnamon oil as an edible coating of
      chicken fillets to prolong its shelf life under refrigeration conditions.
AB  - AIM: The present study was conducted to determine efficacy of edible coating of
      carrageenan and cinnamon oil to enhance the shelf life of chicken meat stored
      under refrigeration conditions. MATERIALS AND METHODS: Chicken breast was coated
      with carrageenan and cinnamon oil by three methods of application viz., spraying
      brushing and dipping. The coated meat was evaluated for drip loss, pH,
      thiobarbituric acid number (TBA), tyrosine value (TV), extract release volume
      (ERV), Warner-Bratzler shear force value (WBSFV), instrumental color,
      microbiological, and sensory qualities as per standard procedures. RESULTS: There
      was a significant difference observed for physicochemical parameters (pH, TBA,
      TV, ERV, drip loss and WBSFV) and microbiological analysis between storage
      periods in all the samples and between the control and treatments throughout the
      storage period but samples did not differed significantly for hunter color
      scores. However, there was no significant difference among three methods of
      application throughout the storage period though dipping had a lower rate of
      increase. A progressive decline in mean sensory scores was recorded along with
      the increase in storage time. CONCLUSION: The carrageenan and cinnamon edible
      coating was found to be a good alternative to enhance the shelf life of chicken
      meat under refrigeration conditions. It was also observed from study that dipping
      method of the application had comparatively higher shelf life than other methods
      of application.

PMID- 27051204
TI  - Isolation, antibiogram and pathogenicity of Salmonella spp. recovered from
      slaughtered food animals in Nagpur region of Central India.
AB  - AIM: To determine the prevalence, antibiogram and pathogenicity of Salmonella
      spp. in the common food animals slaughtered for consumption purpose at government
      approved slaughter houses located in and around Nagpur region during a period of
      2010-2012. MATERIALS AND METHODS: A total of 400 samples comprising 50 each of
      blood and meat from each slaughtered male cattle, buffaloes, pigs and goats were
      collected. Isolation was done by pre-enrichment in buffered peptone water and
      enrichment in Rappaport-Vassiliadis broth with subsequent selective plating onto
      xylose lysine deoxycholate agar. Presumptive Salmonella colonies were
      biochemically confirmed and analyzed for pathogenicity by hemolysin production
      and Congo red dye binding assay (CRDA). An antibiotic sensitivity test was
      performed to assess the antibiotic resistance pattern of the isolates. RESULTS: A
      total of 10 isolates of Salmonella spp. from meat (3 from cattle, 1 from
      buffaloes and 6 from pigs) with an overall prevalence of 5% among food animals
      was recorded. No isolation was reported from any blood samples. Pathogenicity
      assays revealed 100% and 80% positivity for CRDA and hemolytic activity,
      respectively. Antimicrobial sensitivity test showed multi-drug resistance. The
      overall resistance of 50% was noted for trimethoprim followed by ampicillin
      (20%). A maximum sensitivity (80%) was reported to gentamycin followed by 40%
      each to ampicillin and trimethoprim, 30% to amikacin and 10% to kanamycin.
      CONCLUSION: The presence of multidrug resistant and potentially pathogenic
      Salmonella spp. in slaughtered food animals in Nagpur region can be a matter of
      concern for public health.

PMID- 27051205
TI  - Effect of incubation on freezability of cholesterol-loaded cyclodextrin treated
      buffalo (Bubalus bubalis) spermatozoa.
AB  - AIM: The aim of this study was to investigate the effect of incubation on
      freezability of cholesterol loaded cyclodextrin (CLC) treated buffalo
      spermatozoa. MATERIALS AND METHODS: Semen samples with mass motility of 3+ and
      greater, collected from Murrah buffalo bulls were utilized. Immediately after
      collection, four equal groups of semen sample were made. Group I was kept as
      control and diluted with Tris upto concentration of 60*10(6) sperm/ml, where as
      Groups II, III, and IV were treated with CLC at 3 mg/120* 10(6) spermatozoa,
      incubated at 37 degrees C for action of CLC for 10, 15 and 20 min, respectively,
      and diluted with tris upto concentration of 60*10(6) sperm/ml. All groups were
      subjected to equilibration and freezing. The evaluation of semen samples from all
      groups was carried out at fresh, pre-freeze and post-thaw stage for progressive
      motility, viability and hypo-osmotic swelling response (HOS response). RESULTS:
      At the pre-freeze stage, significantly (p<0.05) higher percentage of progressive
      motility and viability was observed in treatment groups as compared to control
      with no significant difference among treatment groups. HOS response was
      significantly (p<0.05) higher in treatment groups as compared to control at pre
      freeze stage. At post-thaw stage, significantly (p<0.05) higher percentage of
      progressive motility, viability and HOS response was recorded in Group II as
      compared to control and other treatment groups (III and IV). Group II retained
      significant post-thaw motility and viability at various post-thaw incubation
      periods. CONCLUSION: Incubation period of 10 min for CLC treated buffalo
      spermatozoa yielded significantly higher results in terms of freezability as
      compared to incubation for 15 and 20 min.

PMID- 27051206
TI  - Awareness, knowledge, and risks of zoonotic diseases among livestock farmers in
      Punjab.
AB  - AIM: The present study was conducted to assess the awareness, knowledge, and
      risks of zoonotic diseases among livestock farmers in Punjab. MATERIALS AND
      METHODS: 250 livestock farmers were selected randomly and interviewed with a
      pretested questionnaire, which contained both open and close ended questions on
      different aspects of zoonotic diseases, i.e., awareness, knowledge, risks, etc.
      Knowledge scorecard was developed, and each correct answer was awarded one mark,
      and each incorrect answer was given zero mark. Respondents were categorized into
      low (mean - 1/2 standard deviation [SD]), moderate (mean +/- 1/2 SD), and high
      knowledge (Mean + 1/2 SD) category based on the mean and SD. The information
      about independent variables viz., age, education, and herd size were collected
      with the help of structured schedule and scales. The data were analyzed by ANOVA,
      and results were prepared to assess awareness, knowledge, and risks of zoonotic
      diseases and its relation with independent variables. RESULTS: Majority of the
      respondents had age up to 40 years (70%), had their qualification from primary to
      higher secondary level (77.6%), and had their herd size up to 10 animals (79.6%).
      About 51.2% and 54.0% respondents had the history of abortion and retained
      placenta, respectively, at their farms. The respondents not only disposed off the
      infected placenta (35.6%), aborted fetus (39.6%), or feces (56.4%) from a
      diarrheic animal but also gave intrauterine medication (23.2%) bare-handedly.
      About 3.6-69.6% respondents consumed uncooked or unpasteurized animal products.
      About 84.8%, 46.0%, 32.8%, 4.61%, and 92.4% of livestock farmers were aware of
      zoonotic nature of rabies, brucellosis, tuberculosis, anthrax, and bird flu,
      respectively. The 55.6%, 67.2%, 52.0%, 64.0%, and 51.2% respondents were aware of
      the transmission of zoonotic diseases to human being through contaminated milk,
      meat, air, feed, or through contact with infected animals, respectively. The
      transmission of rabies through dog bite (98.4%), need of post-exposure
      vaccination (96.8%), and annual vaccination of dogs (78%) were well-known facts
      but only 47.2% livestock owners were aware of the occurrence of abortion due to
      brucellosis and availability of prophylactic vaccine (67.6%) against it as a
      preventive measure. About 69.2% respondents belonged to low to medium knowledge
      level categories, whereas 30.8% respondents had high knowledge (p<0.05) regarding
      different aspects of zoonotic diseases. Age, education, and herd size had no
      significant effect on the knowledge level and awareness of farmers toward
      zoonotic diseases. CONCLUSION: Therefore, from the present study, it may be
      concluded that there is a need to create awareness and improve knowledge of
      livestock farmers toward zoonotic diseases for its effective containment in
      Punjab.

PMID- 27051207
TI  - Effect of feeding different levels of Azolla pinnata on blood biochemicals,
      hematology and immunocompetence traits of Chabro chicken.
AB  - AIM: The present study was conducted to see the effect of feeding different
      levels of Azolla meal on blood biochemicals, hematology and immunocompetence
      traits of Chabro chicken. MATERIALS AND METHODS: The study was conducted on 160
      Chabro chicks, which were randomly divided into four treatment groups each with
      four replicates of 10 birds. The first treatment (T1) served as a control in
      which basal diets was offered without Azolla supplementation while in T2, T3, and
      T4 groups, basal diet was replaced with Azolla meal at 5%, 7.5%, and 10% levels,
      respectively. A feeding trial was conducted upto 8 weeks. At the last week of
      trial, blood samples were collected randomly from one bird of each replicate and
      plasma was separated to estimate certain biochemical parameters, some blood
      metabolites, minerals and enzymes like alanine aminotransferase and aspartate
      aminotransferase (AST). Hematological parameters such as hemoglobin, packed cell
      volume, total leukocytes count and differential leukocytes count were estimated
      in fresh blood just after collection. The humoral immune response was measured
      against sheep red blood cells,and cell-mediated immune response was measured
      against phyto hemagglutinin lectin from Phaseolus vulgaris (PHA-P). RESULTS: The
      study showed that hematological profile of the Chabro bird was not affected by
      any treatment except heterophil and lymphocyte which was found higher in T2 and
      T3 groups and eosinophil was found higher in a T3 group than control. Blood
      glucose, creatinine, cholesterol, total protein, albumin, uric acid, and
      triglycerides were found similar in all the groups and within the normal values
      for broiler chicken. Liver enzymes and macro mineral content in blood were found
      similar in all the treatment groups and within normal physiological range.
      Although AST was found higher in 10% replacement group than control, the value
      was within normal range for broiler chicken. Although antibody titer was found
      similar in all the experimental groups in the present study, cell-mediate immune
      response (response to PHA-P) was found higher in 5%, 7.5%, and 10% replacement
      groups than control(p<0.05). CONCLUSION: Similar blood biochemical parameters and
      higher cell-mediated immune response in Azolla replacement group indicated immune
      modulatory effect of Azolla meal without any toxicity.

PMID- 27051208
TI  - Effect of management system and season on semen freezability in Jakhrana bucks.
AB  - AIM: The objective of the study was to determine the effect of the management
      system (intensive and semi-intensive) and season (autumn and winter) on semen
      freezability in Jakhrana bucks. MATERIALS AND METHODS: A total of 24 Jakhrana
      bucks of same body weight and age (BW=30 kg, age=1 year) were randomly allotted
      into two groups, viz., Group I (intensive system, 12 bucks) and Group II (semi
      intensive system, 12 bucks). These two groups were statistically tested for their
      homogeneity with respect to age and BW. Semen was collected twice weekly using an
      artificial vagina during two seasons: autumn (September-November) and winter
      (December-February). A total of 240 semen samples (120 from each group and
      season) were evaluated for post-thaw motility (PTM), viability, abnormality,
      functional membrane integrity (hypo-osmotic swelling [HOS]) response and
      acrosomal integrity. RESULTS: The mean values of PTM and acrosomal integrity of
      spermatozoa were significantly (p<0.01) higher in Group II as compared to Group
      I. The mean values of viability and abnormality were also differed significant
      (p<0.05) between groups. However, the mean values of HOS response were found non
      significant (p>0.05) between groups. The season showed a significant effect on
      all parameters except viability and HOS response. The PTM and acrosomal integrity
      of spermatozoa were significantly (p<0.01) higher in winter as compared to autumn
      season. Abnormality of spermatozoa was significantly (p<0.05) lower in winter
      season. CONCLUSIONS: This study indicates that both management system and season
      influence semen freezability. The semen collected from bucks reared under the
      semi-intensive system and winter season showed better semen freezability
      characteristics.

PMID- 27051209
TI  - Assessment of motion and kinematic characteristics of frozen-thawed Sirohi goat
      semen using computer-assisted semen analysis.
AB  - AIM: The aim was to determine the motion and kinematics characteristic of frozen
      thawed spermatozoa in Sirohi goat using computer-assisted semen analysis.
      MATERIALS AND METHODS: A study was carried out in Sirohi buck. Semen collection
      was made biweekly from each buck with the help of artificial vagina. A total of
      12 ejaculates were collected from two bucks (six ejaculates from each buck).
      Freshly collected semen was pooled and later evaluated. The pooled semen sample
      was extended with standard glycerolated egg yolk tris extender and later
      subjected to a process of cryopreservation. The motion and kinematic
      characteristics of spermatozoa were studied during freez-thawing process.
      RESULTS: Significantly (p<0.01) higher value of live percent, hypo-osmotic
      swelling test, and acrosomal integrity were recorded in neat semen followed by
      diluted and frozen thaw semen. The proportion of spermatozoa showing slow
      progression were the highest in the neat and diluted semen followed by rapid and
      non-progressively motile, while a reverse pattern was observed in the frozen thaw
      semen where the proportion of non-progressively motile spermatozoa were
      significantly (p<0.01) higher followed by slow and rapid progression. CONCLUSION:
      This study showed that the best results for motion, vitality, plasma membrane
      integrity, and acrosome status were obtained in the neat semen followed by
      diluted and frozen thaw semen. Further, the process of cryopreservation results
      in a shift of motility from slow to non-progressive in the post-thaw semen with a
      significant decrease in the path velocities when compared to neat and diluted
      semen. Hence, it can be concluded that freezing-thawing process reduces the
      motility and kinematic characters spermatozoa and may be an important factor
      affecting the fertilizing ability of spermatozoa resulting in poor conception
      rate after insemination in goats.

PMID- 27051210
TI  - Evaluation of Emblica officinalis fruit powder as a growth promoter in commercial
      broiler chickens.
AB  - AIM: The present study was conducted to evaluate the dietary addition of Emblica
      officinalis (Amla) fruit powder as a growth promoter in commercial broiler
      chickens. MATERIALS AND METHODS: An experiment was conducted on 135 commercial
      broiler chicks (Ven-Cobb 400 strain) divided into three groups with three
      replicates of 15 chicks each. Three treatment groups were as follows - T1: Basal
      diet as per BIS standards; T2: Basal diet supplemented with 0.4% of E.
      officinalis fruit powder; and T3: Basal diet supplemented with 0.8% of E.
      officinalis fruit powder. RESULTS: The average body weights at the end of the
      6(th) week were significantly higher (p<0.05) in groups T2 and T3 compared to
      group T1. Feed intake, feed conversion ratio and feed cost per kg live weight
      production were similar among the treatment groups. The net profit per bird was
      the highest in group T2 (Rs. 19.22/bird) followed by group T3 (Rs. 17.86/bird)
      and the lowest in group T1 (Rs. 14.61/bird). CONCLUSION: Based on the results of
      the present study, it was concluded that dietary addition of E. officinalis
      (Amla) fruit powder had a positive effect on growth performance and net profit
      per bird in commercial broiler chickens.

PMID- 27051211
TI  - Comparison of different diagnostic techniques for the detection of
      cryptosporidiosis in bovines.
AB  - AIM: Aim of the present study was to compare different methods, viz., Sheather's
      sugar flotation (SSF), Ziehl-Neelsen (ZN), Kinyoun's acid-fast method (KAF),
      safranin-methylene blue staining (SMB), and negative staining techniques such as
      nigrosin staining, light green staining, and malachite green staining for the
      detection of Cryptosporidium spp. oocysts in bovines. MATERIALS AND METHODS: A
      total of 455 fecal samples from bovines were collected from private, government
      farms and from the clinical cases presented to Department of Medicine, Veterinary
      College, Bengaluru. They were subjected for SSF, ZN, KAF, SMB and negative
      staining methods. RESULTS: Out of 455 animal fecal samples screened 5.71% were
      found positive for Cryptosporidium spp. oocysts. The species were identified as
      Cryptosporidium parvum in calves and Cryptosporidium andersoni in adults based on
      the morphological characterization and micrometry of the oocysts. CONCLUSIONS: Of
      all the techniques, fecal flotation with sheather's was found to be more specific
      and sensitive method for the detection of Cryptosporidium spp. oocysts. Among the
      conventional staining methods, the SMB gives better differentiation between
      oocysts and yeast. Among the three negative staining methods, malachite green was
      found sensitive over the other methods.

PMID- 27051212
TI  - Effect of extended photoperiod during winter on growth and onset of puberty in
      Murrah buffalo heifers.
AB  - AIM: To investigate the effect of extended photoperiod on growth rate, hormonal
      levels, and puberty in Murrah heifers. MATERIALS AND METHODS: About 14 Murrah
      buffalo heifers were divided into normal day photoperiod (NDP; n=7) and extended
      NDP (ENDP; n=7) groups. The ENDP group was exposed to 4 h of extended photoperiod
      with artificial light (160 lux) after sunset for 3 months during winter. RESULTS:
      Group, age and group-by-age interaction effects on plasma glucose concentrations
      were non-significant (p>0.05). A significant effect of age on non-esterified
      fatty acids (p<0.05), cholesterol (p<0.01), and triglycerides (p<0.05)
      concentrations was observed. Group and group-by-age interaction effects on plasma
      T3, T4, leptin, 17 beta estradiol, prolactin and melatonin concentrations were
      non-significant (p>0.05) while significant (p<0.05) age effect on T4, leptin and
      melatonin concentrations was observed. With respect to the circadian pattern of
      melatonin and prolactin, the group, time and group-by-time interaction effects
      were non-significant (p>0.05). Average daily gain and dry matter intake of
      heifers were non-significant between the NDP and ENDP groups but were
      comparatively higher in ENDP group. By the end of the experiment, 6 out of 7
      heifers attained puberty in ENDP group in comparison to 4 out of 7 in NDP group.
      CONCLUSION: Extending the photoperiod by artificial light for 4 h during winter
      season resulted in better growth rate and early onset of puberty in Murrah
      buffalo heifers.

PMID- 27051214
TI  - Look into research in forensic odontology.

PMID- 27051213
TI  - Isolation and adaptation of bovine herpes virus Type 1 in embryonated chicken
      eggs and in Madin-Darby bovine kidney cell line.
AB  - AIM: Objective of the present study was to isolate bovine herpes virus Type 1
      (BHV-1) from semen of infected bull and to adapt it onto embryonated eggs and
      Madin-Darby bovine kidney (MDBK) cell line. Further, the virus was identified by
      agar gel immunodiffusion (AGID) test. MATERIALS AND METHODS: Semen samples were
      collected from five BHV-1 positive bulls previously confirmed for the presence of
      antibodies against BHV-1 using avidin-biotin enzyme linked immunosorbent assay
      test. The virus from semen samples was adapted in chorioallantoic membrane (CAM)
      of 11-day-old embryonated chickens eggs and in MDBK cell line. The presence of
      BHV-1 in infected CAM and cell culture fluid was confirmed by AGID test. RESULTS:
      Virus infected CAM showed edema, congestion and thickening at first passage
      level. Small foci ranged from 1 to 2 mm in diameter, scattered all over the
      membrane were observed at first passage. More severe changes were observed in CAM
      after serial passaging. The large pock lesions, round in shape with opaque raised
      edge and depressed gray central area of necrosis ranged from 3 to 5 mm in
      diameter were developed at fourth passage. Blind passages in MDBK cell culture
      were made. The MDBK cell line at second passage level showed characteristic
      cytopathic effect viz. rounding of cells with shrinkage, followed by aggregation
      or clumping of cells which progressed rapidly and appeared as "bunch of grapes"
      at 72 h post inoculation. Few cells become elongated when compared with
      uninfected controls. A homogenate of CAM with distinct pock lesions and infected
      cell culture fluid developed precipitation line within 48 h against specific anti
      BHV-1 immune serum by AGID test. CONCLUSION: BHV-1 was easily adapted in CAM of
      chicken embryos and in MDBK cell line. Virus infected CAM and cell culture fluid
      showed precipitin band by AGID test.

PMID- 27051215
TI  - Knowledge and awareness of forensic odontology among dentists in India: A
      systematic review.
AB  - Forensic dentistry involves the processing, review, evaluation, and presentation
      of dental evidence with the purpose of contributing scientific and objective data
      to legal processes. The present, systematic review was conducted to assess
      knowledge and awareness of forensic odontology among dentists in India. A
      systematic review of relevant cross-sectional studies was conducted regarding the
      level of knowledge, awareness, and practical application of forensic odontology
      among dentists in India. Four out of 129 studies were finally included in the
      present review after conducting a search of both electronic and manual scientific
      databases. Potential biases were addressed and the relevant data were extracted
      by the concerned investigators. Almost all the subjects were familiar with the
      subject of forensic odontology in one of the study reports. Only 12% of dentists
      were maintaining complete dental records in the findings of another study. Only
      4% of dentists reported to have contributed to the identification of victims in a
      mass disaster in yet another study. The findings of another study revealed that
      40% of dental practitioners did not have the expertise to identify child abuse.
      The results of the present review showed that the knowledge and awareness level
      of subjects was inadequate and that there is considerable variation in the
      practice of forensic odontology among dentists. It is necessary to expose
      dentists to the basic principles and techniques of the subject. 

PMID- 27051216
TI  - Dentistry to the rescue of missing children: A review.
AB  - Today's society is becoming increasingly unsafe for children: we frequently hear
      about new incidents of missing children, which lead to emotional trauma for the
      loved ones and expose systemic failures of law and order. Parents can take extra
      precautions to ensure the safety of their children by educating them about ways
      to protect themselves and keep important records of the child such as updated
      color photographs, fingerprints, deoxyribonucleic acid (DNA) samples, etc.,
      handy. However, in spite of all efforts, the problem of missing children still
      remains. Developments in the field of dentistry have empowered dentists with
      various tools and techniques to play a pivotal role in tracing a missing child.
      One such tool is Toothprints, a patented arch-shaped thermoplastic dental
      impression wafer developed by Dr. David Tesini, a paediatric dentist from
      Massachusetts. Toothprints enables a unique identification of the missing
      children not only through the bite impression but also through salivary DNA.
      Besides the use of Toothprints, a dentist can assist investigating agencies in
      identifying the missing children in multiple ways, including postmortem dental
      profiling, labeled dental fixtures, DNA extraction from teeth, and serial number
      engraving on the children's teeth. More importantly, all these tools cause
      minimal inconvenience to the individual, making a dentist's role in tracking a
      missing child even more significant. Thus, the simple discipline of maintaining
      timely dental records with the help of their dentists can save potential hassles
      for the parents in the future. 

PMID- 27051217
TI  - Prevalence of a few variant dental features in children aged 11-16 years in
      Davangere, a city in Karnataka.
AB  - CONTEXT: Variations in morphology of shape of teeth have always been of interest
      to dentists from ancient times. But to our surprise, till date, no studies
      related to the prevalence of dental features have been conducted in any part of
      the world. AIMS: To evaluate the prevalence of a few variant dental features in a
      group of children aged from 11 to 16 years in the city of Davangere that belongs
      to the state of Karnataka, India. MATERIALS AND METHODS: A cross-sectional survey
      was conducted where children aged 11-16 years were selected (both girls and boys)
      and type III clinical examination was done. They were checked for the following
      features - Carabelli's cusp, 3-cusped maxillary 2(nd) molar, 5-cusped maxillary
      1(st) molar, 4-cusped mandibular 1(st) molar, 5-cusped mandibular 2(nd) molar,
      cusp 6 present in mandibular 1(st) molar, and 7-cusped mandibular 1(st) molar.
      STATISTICAL ANALYSIS USED: The Chi-square test was used to analyze the
      categorical data. P value of 0.05 or less was considered for statistical
      significance. RESULTS: Around 99.3% of the school children examined had at least
      one of the dental variations that were examined in relation to the shape of
      teeth. CONCLUSIONS: This study definitely provides us with baseline data, but
      further epidemiological studies are required to determine the prevalence of the
      above mentioned dental anomalies.

PMID- 27051218
TI  - DNA isolation from teeth by organic extraction and identification of sex of the
      individual by analyzing the AMEL gene marker using PCR.
AB  - BACKGROUND: To identify the sex of the deceased individual from dental hard
      tissue such as enamel and dentine. OBJECTIVE: To isolate the DNA from dental hard
      tissue (enamel and dentin) from teeth extracted for prophylactic purpose, to
      assess the quality and purity of DNA and to identify the sex using polymerized
      chain reactor (PCR). MATERIALS AND METHODS: DNA was extracted following
      phenol/chloroform (organic) extraction from 20 male and 20 female teeth. The
      samples that contain the amelogenin gene (amel) were amplified by PCR. The
      products of the PCR were run on agarose gel with ethidium bromide staining on gel
      documentation system. RESULTS: The results on the gel showed the presence of X
      specific bands at 212 bp and Y-specific bands at 218 bp. Males were distinguished
      from females by the presence of two bands whereas female samples showed only one,
      that is, X-specific band on the gel. The gender from the known samples was
      determined with complete accuracy, and the results were analyzed statistically by
      the Chi-square test. CONCLUSION: In our study, the PCR-based method showed 100%
      specificity and sensitivity.

PMID- 27051219
TI  - Sexual dimorphism in tooth morphometrics: An evaluation of the parameters.
AB  - AIMS AND OBJECTIVES: Sexual dimorphism refers to the variations in tooth size and
      shape between the sexes. The consistency of these variations is valuable in the
      identification of the sex of an individual in times of mass disaster when whole
      body parts get destroyed or are unavailable. There exist differences in the
      expression of these variables across races and regions. This study aims to
      tabulate and identify the variations in tooth measurements using standarized
      reference points in an attempt to establish parameters of sexual dimorphism.
      MATERIALS AND METHODS: 100 individuals (50 of each sex) in the age group 19-23
      years were assessed for standard morphometric parameters of the maxillary central
      incisor, canine, premolar and molar. Odontometric measurements of established
      parameters were recorded from impression casts of the maxillary jaws. The
      mesiodistal width (MDW), the bucco-ligual width (BLW), the crown length (CL) and
      the cervical angle (CA) were charted among the teeth. The consistency of the
      variations was statistically analyzed and a logistic regression table was
      prepared to identify the sex of the individual from the tooth measurements.
      RESULTS AND CONCLUSIONS: The BLW, MDW and CL reflected significant variations
      among all the teeth to be effective in establishing sexual dimorphism. CA as a
      parameter was inadequate across all the teeth. The permanent maxillary canine was
      the most important tooth to be reflective of the gender and statistically
      significant to be utilized for gender determination.

PMID- 27051220
TI  - Ameloglyphics: A possible forensic tool for person identification following high
      temperature and acid exposure.
AB  - INTRODUCTION: Forensic odontology is a branch that is evolving over time and has
      opened newer avenues that may help in the identification of individuals. Tooth
      prints are the enamel rod end patterns on tooth surface and they are considered
      as a hard tissue analog to fingerprints. Teeth have the highest resistance to
      most environmental effects like fire, desiccation, and decomposition, and may be
      used as a forensic evidence. AIMS AND OBJECTIVES: The aim of the study was to
      evaluate if the tooth prints could be used for an individual's identification and
      reproducibility and permanency of these tooth prints after exposing the teeth to
      acid and various degrees of temperature. MATERIALS AND METHODS: 90 tooth prints
      from 20 freshly extracted maxillary premolar teeth were obtained. Cellophane tape
      technique was used to record enamel rod end patterns on tooth surface. Ten teeth
      (one from each patient) were immersed in 36.46% hydrochloric acid and the tooth
      prints were obtained at various intervals (5 min, 10 min, and 20 min). The other
      10 teeth (one from each patient) were incinerated and impression was made at
      various intervals (80 degrees  C, 400 degrees  C, 600 degrees  C, and 750 degrees
      C). Tooth prints obtained from different teeth (total of 90 tooth prints) were
      analyzed using Verifinger(r) standard SDK version 5.0 software. RESULTS: All the
      20 original tooth prints were distinct from each other and no inter-individual or
      intra-individual similarity was found. The tooth prints from the same tooth after
      it was exposed to acid or heat were reproducible and showed high to very high
      similarity with the original tooth print of that particular tooth stored in the
      database. CONCLUSION: Tooth prints may be used as an effective aid in person
      identification even in adverse conditions such as burn and acid attack injuries.

PMID- 27051221
TI  - Computer-based method of bite mark analysis: A benchmark in forensic dentistry?
AB  - AIM: The study aimed to determine the technique with maximum accuracy in
      production of bite mark overlay. MATERIALS AND METHODS: Thirty subjects (10 males
      and 20 females; all aged 20-30 years) with complete set of natural upper and
      lower anterior teeth were selected for this study after obtaining approval from
      the Institutional Ethical Committee. The upper and lower alginate impressions
      were taken and die stone models were obtained from each impression; overlays were
      produced from the biting surfaces of six upper and six lower anterior teeth by
      hand tracing from study casts, hand tracing from wax impressions of the bite
      surface, radiopaque wax impression method, and xerographic method. These were
      compared with the original overlay produced digitally. RESULTS: Xerographic
      method was the most accurate of the four techniques, with the highest
      reproducibility for bite mark analysis. The methods of wax impression were better
      for producing overlay of tooth away from the occlusal plane. CONCLUSIONS: Various
      techniques are used in bite mark analysis and the choice of technique depends
      largely on personal preference. No single technique has been shown to be better
      than the others and very little research has been carried out to compare
      different methods. This study evaluated the accuracy of direct comparisons
      between suspect's models and bite marks with indirect comparisons in the form of
      conventional traced overlays of suspects and found the xerographic technique to
      be the best.

PMID- 27051222
TI  - Computed tomography based forensic gender determination by measuring the size and
      volume of the maxillary sinuses.
AB  - PURPOSE: Identification of human body or remains after death is a forensic
      procedure, which is difficult to perform and is mandatory by law and in
      compliance with social norms. Sexing the recovered human remains is an integral
      part of the identification process. Maxillary sinus can be used for gender
      determination as it remains intact even when the skull and other bones may be
      badly damaged in casualties where the body is incinerated. Computed tomography
      (CT) provides an excellent method for examining maxillary sinuses. MATERIALS AND
      METHODS: CT images were used to measure the mediolateral, superoinferior, and
      anteroposterior dimensions and the volume of the maxillary sinuses in 30 patients
      (15 males and 15 females) to investigate whether these parameters could be used
      to determine the gender of an individual for forensic identification. The t-test
      for independent samples was used to compare these values in males and females and
      the data were subjected to discriminative analysis using SPSS software. RESULTS:
      Our method was able to predict the gender with an accuracy of 80.0% in males and
      86.7% in females, with an overall accuracy rate of 83.3%. CONCLUSION: The
      accuracy rate in this study was comparable, if not higher than many other methods
      that have been used to predict the gender of an individual from skeletal remains.
      The length, width, height, and volume of the maxillary sinuses together with
      other bones could be used for gender determination with a fair degree of accuracy
      when the whole skeleton is not available.

PMID- 27051223
TI  - Dental age assessment among Tunisian children using the Demirjian method.
AB  - CONTEXT: Since Demirjian system of estimating dental maturity was first
      described, many researchers from different countries have tested its accuracy
      among diverse populations. Some of these studies have pointed out a need to
      determine population-specific standards. AIM: The aim of this study is to
      evaluate the suitability of the Demirjian's method for dental age assessment in
      Tunisian children. MATERIALS AND METHODS: This is a prospective study previously
      approved by the Research Ethics Local Committee of the University Hospital
      Fattouma Bourguiba of Monastir (Tunisia). Panoramic radiographs of 280 healthy
      Tunisian children of age 2.8-16.5 years were examined with Demirjian method and
      scored by three trained observers. STATISTICAL ANALYSIS USED: Dental age was
      compared to chronological age by using the analysis of variance (ANOVA) test.
      Cohen's Kappa test was performed to calculate the intra- and inter-examiner
      agreements. RESULTS: Underestimation was seen in children aged between 9 and 16
      years and the range of accuracy varied from -0.02 to 3 years. The advancement in
      dental age as determined by Demirjian system when compared to chronological age
      ranged from 0.3 to 1.32 year for young males and from 0.26 to 1.37 year for young
      females (age ranged from 3 to 8 years). CONCLUSIONS: The standards provided by
      Demirjian for French-Canadian children may not be suitable for Tunisian children.
      Each population of children may need their own specific standard for an accurate
      estimation of chronological age.

PMID- 27051224
TI  - Denture barcoding in forensic dentistry: A future option.
AB  - Neurodegenerative disorders are commonly seen in elderly individuals. Parkinson's
      disease (PD) is the most common example with memory loss, lack of logic,
      reasoning and analytical thinking. In this case report simple method of 2D Bar
      code technique of denture marking has been explained which will not only useful
      in patients with memory loss but it is very helpful in identifying the
      individuals in case of natural calamities like floods, earthquake, tornedo, state
      of unconsciousness and accidents. Such patients can be traced easily by denture
      barcoding. This technique is a major breakthrough in the field of forensic
      dentistry. 

PMID- 27051225
TI  - Awareness of forensic odontology among police personnel: A new ray of hope in
      forensic odontology.
AB  - BACKGROUND: Police personnel play an important role in collecting and producing
      evidence. Knowledge about the various aspects of forensic as well as dental
      sciences and related evidence in them provide a golden opportunity to forensic
      odontologists to actively participate in the identification of the accused or
      victim. They can also act as an expert witness in court to produce forensic
      dental evidence. AIM: To evaluate the awareness and knowledge about the
      utilization of forensic odontology during evidence collection by the crime scene
      investigation (CSI) officers. MATERIALS AND METHODS: Four hundred police officers
      were included in this survey. A questionnaire was designed to assess the
      awareness and knowledge about forensic odontology and application of the known
      knowledge in identifying and considering the dental evidences. Data were analyzed
      using the software Statistical Package for Social Sciences (SPSS, Chicago, Il,
      USA) version 17.0 by comparing the overall awareness of forensic odontology among
      the trained SI officers and trainee police personnel. RESULTS: The collected
      results showed that there is a requirement for changes in the current practice of
      evidence collection and highlighted the need for better communication between the
      police personnel and forensic odontologists. A significantly higher number of
      police officers in both the trained and trainee groups reported knowledge about
      the subject (P < 0.001) through newspapers and mass media as the sources of
      knowledge. CONCLUSION: Even though the respondents have knowledge about forensic
      odontology, there is a lack of communication and facilities in their system;
      hence, steps must be taken to educate the police personnel about the application
      of forensic odontology.

PMID- 27051226
TI  - Age estimation using intraoral periapical radiographs.
AB  - CONTEXT: Changes in the size of dental pulp caused by the apposition of secondary
      dentin and occlusal wear are morphometric parameters for estimating age. AIM: To
      estimate the accuracy of age evaluation by Kvaal's method and the effect of
      occlusal wear on age using digital intraoral periapical radiographs in a subset
      of the Indian population. MATERIALS AND METHODS: A total of 300 teeth were
      radiographically evaluated using intraoral periapical digital radiographs from 50
      adult patients. A few modifications were made in the design of the study compared
      to the original Kvaal's method. The radiographs of three teeth from each jaw were
      taken and morphometric measurements in ratios were analyzed, which included the
      pulp length to tooth length (X 1), pulp length to root length (X 2), pulp width
      to root widths at three defined levels (X 3), and tooth length to root length (X
      4). STATISTICAL ANALYSIS: The Pearson product-moment correlation coefficient
      (PCC) between age and the morphological variables showed that among them X 1, X
      2, and X 3 were statistically significant but not the tooth root length ratio (X
      4). CONCLUSIONS: The ratios X 1, X 2, and X 3 were good indicators of age and
      hence a multiple linear regression model for age estimation was derived using
      these three variables. However, it was found that X 4 was not a good indicator of
      age estimation in said population.

PMID- 27051227
TI  - Morphometric evaluation of the frontal sinus in relation to age and gender in
      subjects residing in Davangere, Karnataka.
AB  - OBJECTIVE: The main objective of the study was morphometric evaluation of the
      frontal sinus in relation to age and gender and to establish its forensic
      importance and application. MATERIALS AND METHOD: The study group consisted of
      200 subjects (100 males and 100 females) in the age groups 14-20 years, 21-30
      years, 31-45 years, 45 years and above. Posteroanterior (PA) cephalogram
      radiographs were taken using standardized technique. The processed films were
      traced and frontal sinus pattern was established as per Yoshino's classification
      system. RESULTS: The mean values for length, width, and area of the frontal sinus
      were found to be higher in males as compared to females and area of frontal
      sinuses increase with age except in males who were 45 years and above. The left
      width, left area, and bilateral asymmetry in relation to gender was found to be
      statistically significant. CONCLUSION: The morphologic evaluation of frontal
      sinus is a useful technique to determine gender and seems promising in personal
      identification.

PMID- 27051228
TI  - Rugae dimensions and their significance in forensic dentistry.
AB  - BACKGROUND: The palatal rugae are the ridges situated in the anterior part of the
      palatal mucosa, are unique to each individual, and can establish individual's
      identity. AIMS: To establish the reliability of using the palatal rugae
      dimensions in identifying the different ethnic groups. SETTINGS AND DESIGN: Many
      studies have established the reliability of using the palatal rugae patterns in
      identifying the different ethnic groups. However, no studies have been reported
      in the English language literature that uses the rugae dimensions to identify the
      different ethnic groups. MATERIALS AND METHODS: A total of 60 subjects aged
      between 18-30 years comprising of 30 Kannada speaking and 30 Malayalam speaking
      individuals, with 15 males and 15 females, in each were considered for the study.
      The rugae patterns of these patients were traced on dental casts obtained with
      alginate impressions. A digital caliper was used to measure the different
      dimensions of the palatal rugae. STASTICAL ANALYSIS: Statistical analysis was
      carried out using the unpaired 't' test. RESULTS AND CONCLUSION: The present
      study showed a significant difference in the palatal rugae dimensions among the
      Karnataka and Kerala individuals.

PMID- 27051229
TI  - Neuralgias of the Head: Occipital Neuralgia.
AB  - Occipital neuralgia is defined by the International Headache Society as
      paroxysmal shooting or stabbing pain in the dermatomes of the greater or lesser
      occipital nerve. Various treatment methods exist, from medical treatment to open
      surgical procedures. Local injection with corticosteroid can improve symptoms,
      though generally only temporarily. More invasive procedures can be considered for
      cases that do not respond adequately to medical therapies or repeated injections.
      Radiofrequency lesioning of the greater occipital nerve can relieve symptoms, but
      there is a tendency for the pain to recur during follow-up. There also remains a
      substantial group of intractable patients that do not benefit from local
      injections and conventional procedures. Moreover, treatment of occipital
      neuralgia is sometimes challenging. More invasive procedures, such as C2
      gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression,
      neurectomy, and neurolysis with or without sectioning of the inferior oblique
      muscle, are now rarely performed for medically refractory patients. Recently, a
      few reports have described positive results following peripheral nerve
      stimulation of the greater or lesser occipital nerve. Although this procedure is
      less invasive, the significance of the results is hampered by the small sample
      size and the lack of long-term data. Clinicians should always remember that
      destructive procedures carry grave risks: once an anatomic structure is
      destroyed, it cannot be easily recovered, if at all, and with any destructive
      procedure there is always the risk of the development of painful neuroma or
      causalgia, conditions that may be even harder to control than the original
      complaint. 

PMID- 27051230
TI  - Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near
      Janghang Copper Smelter in Korea.
AB  - Concentrations of heavy metals exceed safety thresholds in the soil near Janghang
      Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study
      was conducted to evaluate the level of exposure to toxic metals and the potential
      effect on health in people living near the smelter. The study included 572 adults
      living within 4 km of the smelter and compared them with 413 controls group of
      people living similar lifestyles in a rural area approximately 15 km from the
      smelter. Urinary arsenic (As) level did not decrease according to the distance
      from the smelter, regardless of gender and working history in smelters and mines.
      However, in subjects who had no occupational exposure to toxic metals, blood lead
      (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the
      smelter, both in men and women. Additionally, the distance from the smelter was a
      determinant factor for a decrease of As, Pb, and Cd in multiple regression
      models, respectively. On the other hands, urinary Cd was a risk factor for renal
      tubular dysfunction in populations living near the smelter. These results suggest
      that Janghang copper smelter was a main contamination source of As, Pb, and Cd,
      and populations living near the smelter suffered some adverse health effects as a
      consequence. The local population should be advised to make efforts to reduce
      exposure to environmental contaminants, in order to minimize potential health
      effects, and to pay close attention to any health problems possibly related to
      toxic metal exposure. 

PMID- 27051231
TI  - Occupational Lead Exposure from Indoor Firing Ranges in Korea.
AB  - Military personnel often use ammunitions that contain lead. The present study
      aimed to identify the risks for lead exposure and lead poisoning among workers at
      indoor firing ranges. A special health examination, including blood lead level
      (BLL) testing, was performed for all 120 workers at the indoor firing ranges of
      the Republic of Korea's Air Force, Navy, and Armed Forces Athletic Corps. The
      overall mean BLL was 11.3 +/- 9.4 ug/dL (range: 2.0-64.0 ug/dL). The arithmetic
      mean of the BLL for professional shooters belong to Armed Forces Athletic Corps
      was 14.0 +/- 8.3 ug/dL, while those of shooting range managers and shooting range
      supervisors were 13.8 +/- 11.1 ug/dL and 6.4 +/- 3.1 ug/dL, respectively. One
      individual had a BLL of 64 ug/dL, and ultimately completed chelation treatment
      (with CaNa2-ethylenediaminetetraacetic acid) without any adverse effects. These
      findings indicate that indoor firing range workers are exposed to elevated levels
      of lead. Therefore, when constructing an indoor firing range, a specialist should
      be engaged to design and assess the ventilation system; and safety guidelines
      regarding ammunition and waste handling must be mandatory. Moreover, workplace
      environmental monitoring should be implemented for indoor firing ranges, and the
      workers should undergo regularly scheduled special health examinations. 

PMID- 27051232
TI  - Bone Scintigraphy in the Diagnosis of Rheumatoid Arthritis: Is There Additional
      Value of Bone Scintigraphy with Blood Pool Phase over Conventional Bone
      Scintigraphy?
AB  - We aimed to investigate the value of bone scintigraphy with additional blood pool
      phase (BSBP), compared with conventional bone scintigraphy (CBS), in the
      assessment of rheumatoid arthritis (RA). A total of 242 patients (43 males, 199
      females; 14-78 years) with arthralgia, and underwent BSBP were retrospectively
      analyzed. On the first physical examination, active arthritis was found in 128 of
      the 242 patients. Clinical diagnosis was made by a rheumatologist on the basis of
      the 1987 American College of Rheumatology (ACR) criteria, which are considered to
      be the gold standard. The diagnostic performances and prognostic value of BSBP
      and CBS were analyzed in the total patients with arthralgia and in the patients
      with arthritis. The sensitivity of BSBP (84.2%, 80/95) were significantly higher
      than that of CBS (74.8%, 72/95) in the patients with arthralgia (P = 0.039). When
      BSBP was interpreted with the results of elevated/positive anti-CCP antibody, its
      accuracy over CBS also became significantly higher (86.0%, 208/242 vs. 83.1%,
      201/242 respectively, P = 0.021). The diagnostic odds ratio of BSBP positivity
      was higher than CBS positivity in the patients with arthralgia (26.0, 12.9-52.4
      vs. 21.1, 10.8-41.3) and with arthritis (12.0, 4.9-29.4 vs. 10.0, 4.2-23.4). Both
      BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic
      performance for diagnosis of RA. However, in the patients with arthralgia, BSBP
      was found to be more sensitive than CBS and more accurate when interpreted with
      the result of anti-CCP antibody. This could help physicians diagnose RA in daily
      clinical practice. 

PMID- 27051233
TI  - Pretreatment Lymphopenia, Poor Performance Status, and Early Courses of Therapy
      Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma
      during Treatment with Bortezomib-based Regimens.
AB  - The aim of this study was to identify the risk factors associated with severe
      bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with
      bortezomib-based regimens. A total of 98 patients with MM were evaluated during
      427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during
      19.0% (81/427) of the treatment courses. In the multivariate analysis for the
      factors associated with the development of SBI in each treatment course, poor
      performance status (Eastern Cooperative Oncology Group >= 2, P < 0.001), early
      course of therapy (<= 2 courses, P < 0.001), and pretreatment lymphopenia
      (absolute lymphocyte count < 1.0 * 10(9)/L, P = 0.043) were confirmed as
      independent risk factors. The probability of developing SBI were 5.1%, 14.9%,
      23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P <
      0.001). In conclusion, we identified three pretreatment risk factors associated
      with SBI in each course of bortezomib treatment. Therefore, MM patients with
      these risk factors should be more closely monitored for the development of SBI
      during bortezomib-based treatment. 

PMID- 27051234
TI  - Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of
      Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.
AB  - The clinical significance of prolonged PR interval has not been evaluated in
      patients with frequent premature atrial contractions (PACs). We investigated
      whether prolonged PR interval could predict new occurrence of atrial fibrillation
      (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients
      with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter
      monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684
      patients, 626 patients had normal PR intervals (group A) and 58 patients had
      prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14
      patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group
      A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard
      ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006
      1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012
      1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval,
      advanced age, and enlarged LA dimension are independent risk factors of AF
      occurrence in patients with frequent PACs. 

PMID- 27051235
TI  - Type 2 Diabetes Induces Prolonged P-wave Duration without Left Atrial
      Enlargement.
AB  - Prolonged P-wave duration has been observed in diabetes. However, the underlying
      mechanisms remain unclear. The aim of this study was to elucidate the possible
      mechanisms. A rat model of type 2 diabetes mellitus (T2DM) was used. P-wave
      durations were obtained using surface electrocardiography and sizes of the left
      atrium were determined using echocardiography. Cardiac inward rectifier K(+)
      currents (Ik1), Na(+) currents (INa), and action potentials were recorded from
      isolated left atrial myocytes using patch clamp techniques. Left atrial tissue
      specimens were analyzed for total connexin-40 (Cx40) and connexin-43 (Cx43)
      expression levels on western-blots. Specimens were also analyzed for Cx40 and
      Cx43 distribution and interstitial fibrosis by immunofluorescent and Masson
      trichrome staining, respectively. The mean P-wave duration was longer in T2DM
      rats than in controls; however, the mean left atrial sizes of each group of rats
      were similar. The densities of Ik1 and INa were unchanged in T2DM rats compared
      to controls. The action potential duration was longer in T2DM rats, but there was
      no significant difference in resting membrane potential or action potential
      amplitude compared to controls. The expression level of Cx40 protein was
      significantly lower, but Cx43 was unaltered in T2DM rats. However,
      immunofluorescent labeling of Cx43 showed a significantly enhanced
      lateralization. Staining showed interstitial fibrosis was greater in T2DM atrial
      tissue. Prolonged P-wave duration is not dependent on the left atrial size in
      rats with T2DM. Dysregulation of Cx40 and Cx43 protein expression, as well as
      fibrosis, might partly account for the prolongation of P-wave duration in T2DM. 

PMID- 27051236
TI  - Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated
      Protein Kinase.
AB  - Angiotensin II (Ang II) induces the pathological process of vascular structures,
      including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In
      kidneys, Ang II plays an important role in the development of proteinuria by the
      modification of podocyte molecules. We have previously found that Ang II
      suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1
      receptor and MAPK signaling pathway. In the present study, we investigated the
      roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse
      podocytes and treated them with various concentrations of Ang II and AMPK
      modulating agents and analyzed the changes of p130Cas by confocal imaging and
      western blotting. In immunofluorescence study, Ang II decreased the intensity of
      p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear
      areas in a concentrated pattern in podocytes. Ang II also reduced the amount of
      p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR,
      restored the suppressed and mal-localized p130Cas significantly, whereas,
      compound C, an AMPK inhibitor, further aggravated the changes of p130Cas.
      Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of
      p130Cas suppressed by Ang II. These results suggest that Ang II induces the
      relocalization and suppression of podocyte p130Cas by the suppression of AMPK via
      Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.

PMID- 27051237
TI  - Long-term Prognosis of Anti-Neutrophil Cytoplasmic Antibody-Negative Renal
      Vasculitis: Cohort Study in Korea.
AB  - Few studies have reported on the long-term prognosis of anti-neutrophil
      cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and
      December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA
      status was tested using indirect immunofluorescence and enzyme-linked
      immunosorbent assays. During a median (interquartile range) follow-up duration of
      933.5 (257.5-2,079.0) days, 41.7% of patients progressed to end stage renal
      disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA
      negative and positive, respectively. The rate of ESRD within 3 months was higher
      in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan
      Meier survival analysis, ANCA-negative patients showed shorter renal survival
      than did ANCA-positive patients (log-rank P = 0.033). In univariate Cox
      proportional hazard regression analysis, ANCA-negative patients showed increased
      risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028-9.895, P
      = 0.045). However, the effect of ANCA status on renal survival was not
      statistically significant in multivariate analysis. Finally, ANCA status did not
      significantly affect patient survival. In conclusion, long-term patient and renal
      survival of ANCA-negative renal vasculitis patients did not differ from those of
      ANCA-positive renal vasculitis patients. Therefore, different treatment strategy
      depending on ANCA status might be unnecessary. 

PMID- 27051238
TI  - The Glucotoxicity Protecting Effect of Ezetimibe in Pancreatic Beta Cells via
      Inhibition of CD36.
AB  - Inhibition of CD36, a fatty acid transporter, has been reported to prevent
      glucotoxicity and ameliorate high glucose induced beta cell dysfunction.
      Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann
      Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We
      attempted to clarify the beneficial effect of ezetimibe on insulin secreting
      cells and to determine whether this effect is related to change of CD36
      expression. mRNA expression of insulin and CD36, intracellular peroxide level and
      glucose stimulated insulin secretion (GSIS) under normal (5.6 mM) or high glucose
      (30 mM) condition in INS-1 cells and primary rat islet cells were compared.
      Changes of the aforementioned factors with treatment with ezetimibe (20 MUM)
      under normal or high glucose condition were also assessed. mRNA expression of
      insulin was decreased with high glucose, which was reversed by ezetimibe in both
      INS-1 cells and primary rat islets. CD36 mRNA expression was increased with high
      glucose, but decreased by ezetimibe in INS-1 cells and primary rat islets. Three
      day treatment with high glucose resulted in an increase in intracellular peroxide
      level; however, it was decreased by treatment with ezetimibe. Decrease in GSIS by
      three-day treatment with high glucose was reversed by ezetimibe. Palmitate uptake
      following exposure to high glucose conditions for three days was significantly
      elevated, which was reversed by ezetimibe in INS-1 cells. Ezetimibe may prevent
      glucotoxicity in pancreatic beta-cells through a decrease in fatty acid influx
      via inhibition of CD36. 

PMID- 27051239
TI  - Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the
      First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study
      Team Cohort.
AB  - The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD
      Subgroup Study team, KOCOSS) is a multicenter observational study that includes
      956 patients (mean age 69.9 +/- 7.8 years) who were enrolled from 45 tertiary and
      university-affiliated hospitals from December 2011 to October 2014. The initial
      evaluation for all patients included pulmonary function tests (PFT), 6-minute
      walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research
      Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's
      Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline
      characteristics between patients with early- (Global Initiative for Chronic
      Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage
      COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post
      bronchodilator FEV1 was 55.8% +/- 16.7% of the predicted value, and most of the
      patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number
      of exacerbations during one year prior to the first visit was significantly lower
      in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score
      (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total
      score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001).
      Common comorbidities among all patients were hypertension (323, 37.7%), diabetes
      mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with
      early COPD will provide important information towards early detection, proper
      initial management, and design of future studies. 

PMID- 27051240
TI  - Neurologic Manifestations of Enterovirus 71 Infection in Korea.
AB  - Enterovirus 71 frequently involves the central nervous system and may present
      with a variety of neurologic manifestations. Here, we aimed to describe the
      clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal
      fluid (CSF) profiles of patients presenting with neurologic complications of
      enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric
      patients hospitalized with acute neurologic manifestations accompanied by
      confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and
      2014. The patients' mean age was 2.9 +/- 5.5 years (range, 18 days to 12 years),
      and 80.6% of patients were less than 4 years old. Based on their clinical
      features, the patients were classified into 4 clinical groups: brainstem
      encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute
      flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus
      (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia
      (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of
      these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in
      the posterior region of the brainstem and bilateral cerebellar dentate nuclei.
      Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%)
      recovered completely without any neurologic deficits; one patient (3.2%) died due
      to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis
      was the most common neurologic manifestation of enterovirus 71 infection. The
      characteristic clinical symptoms such as myoclonus, ataxia, and tremor in
      conjunction with CSF pleocytosis and brainstem lesions on MR images are
      pathognomonic for diagnosis of neurologic involvement by enterovirus 71
      infection. 

PMID- 27051241
TI  - Regional Deprivation Index and Socioeconomic Inequalities Related to Infant
      Deaths in Korea.
AB  - Deprivation indices have been widely used to evaluate neighborhood socioeconomic
      status and therefore examine individuals within their regional context. Although
      some studies on the development of deprivation indices were conducted in Korea,
      additional research is needed to construct a more valid and reliable deprivation
      index. Therefore, a new deprivation index, named the K index, was constructed
      using principal component analysis. This index was compared with the Carstairs,
      Townsend and Choi indices. A possible association between infant death and
      deprivation was explored using the K index. The K index had a higher correlation
      with the infant mortality rate than did the other three indices. The regional
      deprivation quintiles were unequally distributed throughout the country. Despite
      the overall trend of gradually decreasing infant mortality rates, inequalities in
      infant deaths according to the deprivation quintiles persisted and widened.
      Despite its significance, the regional deprivation variable had a smaller effect
      on infant deaths than did individual variables. The K index functions as a
      deprivation index, and we may use this index to estimate the regional
      socioeconomic status in Korea. We found that inequalities in infant deaths
      according to the time trend persisted. To reduce the health inequalities among
      infants in Korea, regional deprivation should be considered. 

PMID- 27051242
TI  - Effect of Breastfeeding Duration on Cognitive Development in Infants: 3-Year
      Follow-up Study.
AB  - We investigated the association between breastfeeding and cognitive development
      in infants during their first 3 years. The present study was a part of the
      Mothers' and Children's Environmental Health (MOCEH) study, which was a multi
      center birth cohort project in Korea that began in 2006. A total of 697 infants
      were tested at age 12, 24, and 36 months using the Korean version of the Bayley
      Scales of Infant Development II (K-BSID-II). The use and duration of
      breastfeeding and formula feeding were measured. The relationship between
      breastfeeding and the mental development index (MDI) score was analyzed by
      multiple linear regression analysis. The results indicated a positive correlation
      between breastfeeding duration and MDI score. After adjusting for covariates,
      infants who were breastfed for >= 9 months had significantly better cognitive
      development than those who had not been breastfed. These results suggest that the
      longer duration of breastfeeding improves cognitive development in infants. 

PMID- 27051243
TI  - Effects of Omega-3 Fatty Acids on Erectile Dysfunction in a Rat Model of
      Atherosclerosis-induced Chronic Pelvic Ischemia.
AB  - The aim of this study was to investigate whether the omega-3 fatty acids help to
      improve erectile function in an atherosclerosis-induced erectile dysfunction rat
      model. A total of 20 male Sprague-Dawley rats at age 8 weeks were divided into
      three groups: Control group (n = 6, untreated sham operated rats), Pathologic
      group (n = 7, untreated rats with chronic pelvic ischemia [CPI]), and Treatment
      group (n = 7, CPI rats treated with omega-3 fatty acids). For the in vivo study,
      electrical stimulation of the cavernosal nerve was performed and erectile
      function was measured in all groups. Immunohistochemical antibody staining was
      performed for transforming growth factor beta-1 (TGF-beta1), endothelial nitric
      oxide synthase (eNOS), and hypoxia inducible factor 1-alpha (HIF-1alpha). In vivo
      measurement of erectile function in the Pathologic group showed significantly
      lower values than those in the Control group, whereas the Treatment group showed
      significantly improved values in comparison with those in the Pathologic group.
      The results of western blot analysis revealed that systemically administered
      omega-3 fatty acids ameliorated the cavernosal molecular environment. Our study
      suggests that omega-3 fatty acids improve intracavernosal pressure and have a
      beneficial role against pathophysiological consequences such as fibrosis or
      hypoxic damage on a CPI rat model, which represents a structural erectile
      dysfunction model. 

PMID- 27051244
TI  - A Multicenter Study Investigating Empathy and Burnout Characteristics in Medical
      Residents with Various Specialties.
AB  - We assessed empathy in medical residents, including factors modifying empathy and
      the relationship between empathy and burnout. Participants (n = 317 residents,
      response rate = 42%) from 4 university hospitals completed a socio-demographic
      questionnaire, the Jefferson Scale of Empathy (Health Professional version,
      Korean edition), and the Maslach Burnout Inventory (MBI). Participants were
      classified by medical specialty: "people-oriented specialty" (POS group) or
      "technology-oriented specialty" (TOS group), with more women in the POS than in
      the TOS group, chi(2) = 14.12, P < 0.001. Being female, married, and having
      children were factors related to higher empathy (gender, t = -2.129, P = 0.034;
      marriage, t = -2.078, P = 0.038; children, t = 2.86, P = 0.005). Within specialty
      group, POS residents showed higher empathy scores in the fourth as compared to
      the first year, F = 3.166, P = 0.026. Comparing POS and TOS groups by year,
      fourth year POS residents had significantly higher scores than did fourth year
      TOS residents, t = 3.349, P = 0.002. There were negative correlations between
      empathy scores and 2 MBI subscales, emotional exhaustion (EE) and
      depersonalization (DP). Additionally, first year POS residents had higher DP
      scores than did first year TOS residents, t = 2.183, P = 0.031. We suggest that
      factors important for empathy are type of medical specialty, marriage, siblings,
      and children. Burnout state may be related to decreasing empathy. 

PMID- 27051245
TI  - The Impact of Celebrity Suicide on Subsequent Suicide Rates in the General
      Population of Korea from 1990 to 2010.
AB  - The association between celebrity suicide and subsequent increase in suicide
      rates among the general population has been suggested. Previous studies primarily
      focused on celebrity suicides in the 2000s. To better understand the association,
      this study examined the impacts of celebrity suicides on subsequent suicide rates
      using the data of Korean celebrity suicides between 1990 and 2010. Nine celebrity
      suicides were selected by an investigation of media reports of suicide deaths
      published in three major newspapers in Korea between 1990 and 2010. Suicide
      mortality data were obtained from the National Statistical Office of Korea.
      Seasonal autoregressive integrated moving average models with intervention
      analysis were used to test the impacts of celebrity suicides, controlling for
      seasonality. Six of the 9 celebrity suicides had significant impacts on suicide
      rates both in the total population and in the same gender- or the same age
      subgroups. The incident that occurred in the 1990s had no significant impact on
      the overall suicide rates, whereas the majority of the incidents in the 2000s had
      significant influences for 30 or 60 days following each incident. The influence
      of celebrity suicide was shown to reach its peak following the suicide death of a
      renowned actress in 2008. The findings may suggest a link between media coverage
      and the impact of celebrity suicide. Future studies should focus more on the
      underlying processes and confounding factors that may contribute to the impact of
      celebrity suicide on subsequent suicide rates. 

PMID- 27051246
TI  - Body Composition, Sarcopenia, and Suicidal Ideation in Elderly Koreans: Hallym
      Aging Study.
AB  - This study was conducted to assess the relationship between body composition and
      suicidal ideation among the Korean elderly population (n = 302; >= 65 years) who
      participated in the Hallym Aging Study in 2010. Body composition was measured
      using dual-energy X-ray absorptiometry, and obesity was measured by the indices
      of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR),
      waist-to-height ratio (WHtR), and body fat percentage. Sarcopenia was defined as
      presence of both low muscle mass and low muscle function. Suicidal ideation was
      assessed using the Beck Scale for Suicide Ideation. We found no differences in
      body composition measures between subjects with suicidal ideation and those
      without. In the logistic regression analyses, there were no significant
      relationships for suicidal ideation according to body composition measures,
      including BMI, WC, WHR, WHtR, and body fat percentage in both sexes. After
      adjusting for age, smoking status, alcohol drinking, regular exercise, medical
      comorbidities, monthly income, education level, and presence of depressive
      symptoms, the odds ratio (OR) of suicidal ideation was higher in elderly men with
      sarcopenia compared to those without, whereas no significant relationships were
      observed in elderly women (OR 8.28, 95% confidence interval [CI] 1.20-61.34 in
      men; OR 0.79, 95% CI 0.07-8.43 in women). Sarcopenia is closely associated with
      an increased risk of suicidal ideation in elderly men. 

PMID- 27051247
TI  - Naturalistic Pharmacotherapy Compliance among Pediatric Patients with Attention
      Deficit/Hyperactivity Disorder: a Study Based on Three-Year Nationwide Data.
AB  - We examined short- and long-term medication compliance among youth with attention
      deficit hyperactivity disorder (ADHD), using data from the National Health
      Insurance database in Korea. Of the 5,699,202 6-14-year-old youth in 2008, we
      chose those with at least 1 medical claim containing an ICD-10 code for diagnosis
      of ADHD (F90.0) and no prescription for ADHD within the previous 365 days. We
      tracked the data every 6 months between 2008 and 2011, to determine treatment
      compliance among newly diagnosed, medicated patients. Further, we checked every 1
      month of the 6 months after treatment commencement. Treatment continuity for each
      patient was calculated by sequentially counting the continuous prescriptions. For
      measuring compliance, we applied the medication possession ratio (MPR) as 0.6,
      0.7, and 0.8, and the gap method as 15- and 30-days' intervals. There were 15,133
      subjects; 11,934 (78.86%) were boys. Overall 6-month treatment compliance was
      59.0%, 47.3%, 39.9%, 34.1%, 28.6%, and 23.1%. Monthly drop-out rates within the
      first 6 months were 20.6%, 6.5%, 4.7%, 3.7%, 3.0%, and 2.5%, respectively. When
      applying MPR more strictly or shorter gap days, treatment compliance lessened.
      This is the first nationwide report on 36-month treatment compliance of the whole
      population of 6-14-year-olds with ADHD. We found the beginning of the treatment,
      especially the first month, to be a critical period in pharmacotherapy. These
      results also suggest the importance of setting appropriate treatment adherence
      standards for patients with ADHD, considering the chronic course of ADHD. 

PMID- 27051248
TI  - Clinical Significance of the Number of Depressive Symptoms in Major Depressive
      Disorder: Results from the CRESCEND Study.
AB  - Our study aimed to establish the relationship between the number of depressive
      symptoms and the clinical characteristics of major depressive disorder (MDD).
      This would enable us to predict the clinical significance of the number of
      depressive symptoms in MDD patients. Using data from the Clinical Research Center
      for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were
      recruited. The baseline and clinical characteristics of groups with different
      numbers of depressive symptoms were compared using the chi(2) test for discrete
      variables and covariance (ANCOVA) for continuous variables. In addition, the
      scores of these groups on the measurement tools were compared by ANCOVA after
      adjusting the potential effects of confounding variables. After adjusting the
      effects of monthly income and history of depression, a larger number of
      depressive symptoms indicated higher overall severity of depression (F [4, 756] =
      21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145,
      P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal
      ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of
      social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656]
      = 11.975, P < 0.001). However, there were no significant differences in alcohol
      consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms
      can be used as an index of greater illness burden in clinical psychiatry. 

PMID- 27051249
TI  - Epidemiologic Aspects of Medical Retirement from the Republic of Korea Army due
      to Visual Impairment.
AB  - This study was done to report the epidemiologic characteristics of medical
      retirement from the Republic of Korea (ROK) Army due to visual impairment and to
      suggest a practical screening system for the draft. The medical records of 423
      eyes of 301 patients who retired from the ROK Army due to visual impairment were
      reviewed retrospectively between January 2010 and December 2014. The patients
      were grouped by the presence of trauma, and each group was subdivided by military
      rank. We analyzed demographic and ophthalmic data, including the etiology of
      ophthalmologic disease. The etiology was classified into 5 anatomical categories
      (ocular surface, lens, retina, optic nerve and extraocular visual pathway, and
      extraocular muscle and orbit), which were then subdivided into the type of
      disease. The mean age was 24.5 years, and non-traumatic mechanisms accounted for
      81.1% (343/423 eyes) of medical retirements. Visual acuity was better in patients
      without trauma. In enlisted soldiers, disease in the optic nerve and extraocular
      visual pathway was the most common anatomical category (40.5%), and primary open
      angle glaucoma (30.8%), retinal dystrophy (18.3%), congenital cataract (14.5%),
      and retinal detachment (9.7%) were the four most common diseases. Most medical
      retirements due to visual impairment resulted from non-traumatic mechanisms, even
      though patients were young. The fundus examination and visual field test would be
      more useful tools than a conventional vision test for large-scale draft screening
      for the most common two disease types: primary open angle glaucoma and retinal
      dystrophy. 

PMID- 27051250
TI  - Incidence and Mortality after Distal Radius Fractures in Adults Aged 50 Years and
      Older in Korea.
AB  - The purpose of this study was to assess the incidence and mortality of distal
      radius fracture among patients 50 years of age and older with diagnosis code
      (ICD10; S52.5, S52.6) and treatment code using a nationwide claims database from
      2008 to 2012. All patients were followed using patient identification code to
      identify deaths. Standardized mortality ratios (SMRs) of distal radius fracture
      were calculated based on age and gender-specific rates in the entire Korean
      population. The number of distal radius fractures increased by 54.2% over the 5
      year study (48,145 in 2008 and 74,240 in 2012). The incidence of distal radius
      fracture increased from 367.4/100,000 in 2008 to 474.1/100,000 in 2012. The
      cumulative mortality rate over the first 12 months after distal radius fracture
      was decreased from 2.0% (968/48,145) in 2008 to 1.4% (1,045/74,240) in 2012. The
      mean year mortality over 5 years in men (2.6%, 1,279/50,128) over the first 12
      months was 1.7-times higher than in women (1.5%, 3,952/257,045). The mean of SMR
      of distal radius fracture at 1 year post-fracture was 1.45 in men and 1.17 in
      women. This study using a nationwide database demonstrates that the distal radius
      fractures are increasing with a decreasing mortality in Korea. 

PMID- 27051251
TI  - A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy
      Results.
AB  - A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus
      (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray,
      and the patient was placed on a mechanical ventilator because of progressive
      respiratory failure. Urinary protein excretion steadily increased for a
      microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine
      ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum
      creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks
      after the onset of symptoms. Acute tubular necrosis was the main finding, and
      proteinaceous cast formation and acute tubulointerstitial nephritis were found.
      There were no electron dense deposits observed with electron microscopy. We could
      not verify the virus itself by in situ hybridization and confocal microscopy
      (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary
      virus excretion, and timely kidney biopsy results should be investigated with
      thorough precautions to reveal the direct effects of MERS-CoV with respect to
      renal complications. 

PMID- 27051252
TI  - Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib
      Fracture.
AB  - Delayed hemothorax after blunt torso injury is rare, but might be associated with
      significant morbidity and mortality. We present a case of delayed hemothorax
      bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered
      from multiple rib fractures on the right side, a right hemopneumothorax, thoracic
      vertebral injury and a pelvic bone fracture after a fall from a fourth floor
      window. Delayed hemothorax associated with phrenic artery bleeding, caused by a
      stab injury from a fractured rib segment, was treated successfully by a minimally
      invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib
      or ribs might be accompanied by delayed massive hemothorax that can be rapidly
      identified and promptly managed by thoracoscopic means. 

PMID- 27051253
TI  - Letter to the Editor: Patients' Knowledge and Decisional Conflict Regarding
      Tamoxifen Use: Scientific Views.

PMID- 27051254
TI  - The Author's Response: Assessment of Breast Cancer Patients' Knowledge and
      Decisional Conflict Regarding Tamoxifen Use.

PMID- 27051255
TI  - Surgical Outcomes of Balanced Deep Lateral and Medial Orbital Wall Decompression
      in Korean Population: Clinical and Computed Tomography-based Analysis.
AB  - PURPOSE: To evaluate the clinical outcomes of balanced deep lateral and medial
      orbital wall decompression and to estimate surgical effects using computed
      tomography (CT) images in Korean patients with thyroid-associated ophthalmopathy
      (TAO). METHODS: Retrospective chart review was conducted in TAO patients with
      exophthalmos who underwent balanced deep lateral and medial orbital wall
      decompression. Exophthalmos was measured preoperatively and postoperatively at 1
      and 3 months. Postoperative complications were evaluated in all study periods. In
      addition, decompressed bone volume was estimated using CT images. Thereafter,
      decompression volume in each decompressed orbital wall was analyzed to evaluate
      the surgical effect and predictability. RESULTS: Twenty-four patients (48 orbits)
      with an average age of 34.08 +/- 7.03 years were evaluated. The mean preoperative
      and postoperative exophthalmos at 1 and 3 months was 18.91 +/- 1.43, 15.10 +/-
      1.53, and 14.91 +/- 1.49 mm, respectively. Bony decompression volume was 0.80 +/-
      0.29 cm(3) at the medial wall and 0.68 +/- 0.23 cm(3) at the deep lateral wall.
      Postoperative complications included strabismus (one patient, 2.08%), upper
      eyelid fold change (four patients, 8.33%), and dysesthesia (four patients,
      8.33%). Postsurgical exophthalmos reduction was more highly correlated with the
      deep lateral wall than the medial wall. CONCLUSIONS: In TAO patients with
      exophthalmos, balanced deep lateral and medial orbital wall decompression is a
      good surgical method with a low-risk of complications. In addition, deep lateral
      wall decompression has higher surgical predictability than medial wall
      decompression, as seen with CT analysis.

PMID- 27051256
TI  - Factors Affecting Long-term Myopic Regression after Laser In Situ Keratomileusis
      and Laser-assisted Subepithelial Keratectomy for Moderate Myopia.
AB  - PURPOSE: High myopia is known to be a risk factor for long-term regression after
      laser refractive surgery. There have been few studies about the correction of
      moderate myopias that did not need retreatment after long-term follow-up. We
      evaluated 10 years of change in visual acuity and refractive power in eyes with
      moderate myopia after laser refractive surgery. METHODS: We included patients
      that had undergone laser in situ keratomileusis (LASIK) or laser-assisted
      subepithelial keratectomy (LASEK) to correct their myopia and that had at least
      10 years of follow-up. We evaluated the stability of visual acuity in terms of
      safety, efficacy, and refractive changes at examinations 6 months and 1, 2, 5, 7,
      and 10 years after surgery. RESULTS: The study evaluated 62 eyes (36 eyes in
      LASIK patients and 26 eyes in LASEK patients). In both groups, the efficacy index
      tended to decrease, and it was consistently higher in the LASEK group compared to
      the LASIK group over the 10 years of follow-up. The safety index improved over 10
      years and was always higher than 0.9 in both groups. The difference between the
      spherical equivalent at 6 months postoperatively and later periods was
      statistically significant after 5, 7, and 10 years in both groups (LASIK, p =
      0.036, p = 0.003, and p < 0.001, respectively; LASEK, p = 0.006, p = 0.002, and p
      = 0.001, respectively). Ten years after surgery,26 eyes (66.7%) in the LASIK
      group and 19 eyes (73.1%) in the LASEK group had myopia greater than 1 diopter.
      In comparison with the thickness at 6 months postoperatively, central corneal
      thickness was significantly increased after 5, 7, and 10 years in both LASIK and
      LASEK groups (LASIK, p < 0.001, p < 0.001, and p < 0.001, respectively; LASEK, p
      = 0.01, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: Moderately myopic
      eyes showed progressive myopic shifting and corneal thickening after LASIK and
      LASEK during 10 years of follow-up. We also found that early refractive
      regression may indicate the long-term refractive outcome.

PMID- 27051257
TI  - Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal
      Erosions.
AB  - PURPOSE: To evaluate the effect of platelet-rich plasma (PRP) eye drops in the
      treatment of recurrent corneal erosions (RCE). METHODS: A total of 47 eyes were
      included in this retrospective study. Clinical records of 20 consecutive patients
      with RCE who had been treated with conventional lubricant eye drops (conventional
      treatment group) from June 2006 to December 2008 and 27 consecutive patients
      treated with autologous PRP eye drops in addition to lubricant eye drops (PRP eye
      drops treated group) from January 2009 to September 2014 were reviewed. Major and
      minor recurrences were recorded and compared between two groups. RESULTS: This
      study included 31 men and 16 women. The mean age was 44.5 +/- 14.5 years (range,
      19 to 86 years), and the mean follow-up duration was 14.9 +/- 14.4 months (range,
      6 to 64 months). Of the 27 cases in the PRP eye drops treated group, there were
      seven major recurrences in six eyes (22.2%) and ten minor recurrences in seven
      eyes (25.9%). In contrast, 16 eyes (80.0%) from the 20 patients in the
      conventional lubricant eye drops treated group had major recurrences, and all
      patients in this group reported minor recurrences. The mean frequency of
      recurrence was 0.06 +/- 0.08 per month in the PRP eye drops treated group and
      0.39 +/- 0.24 per month in the conventional treatment group (p = 0.003). No side
      effects were noted in any of the patients over the follow-up period. CONCLUSIONS:
      The use of PRP eye drops for the treatment of RCE was shown to be effective in
      reducing the recurrence rate without any significant complications.

PMID- 27051258
TI  - Short-term Clinical Outcomes after Transscleral Fixation Using the Intrascleral
      Pocket Technique: A Retrospective Cohort Study Analysis.
AB  - PURPOSE: To compare the two transscleral fixation (TSF) techniques of
      intrascleral pocket and conventional scleral flap with conjunctival division
      techniques in terms of short-term clinical effects. METHODS: This retrospective
      cohort study included all consecutive patients with aphakia in Gyeongsang
      National University Hospital in Jinju, Korea, who underwent TSF between January
      2012 and December 2014. The medical records of all patients were retrospectively
      reviewed, and the endothelial cell count (ECC), refraction, best-corrected visual
      acuity (BCVA), intraocular pressure, slit lamp, and fundus examination results
      before and 1 day and 6 months after surgery were recorded. The postoperative
      complications and visual outcomes were also recorded. RESULTS: The intrascleral
      pocket and conventional-flap groups did not differ significantly in terms of
      demographics, presurgical BCVA, or ECC. However, the intrascleral pocket group
      had a significantly lower BCVA at 1 day and 6 months after surgery compared to
      the conventional-flap group. The two groups did not differ in terms of ECC 6
      months after surgery. The intrascleral pocket group had no postoperative
      complications, but five patients in the conventional-flap group complained of
      irritation. In both groups, the intraocular lens was well positioned without
      tilting or subluxation, and astigmatism was significantly reduced at 1 day and 6
      months after surgery. CONCLUSIONS: The intrascleral pocket technique of TSF does
      not involve conjunctival dissection and is a successful method of sulcus
      fixation. It stably corrects the intraocular lens and is easy to perform, which
      helps to reduce operation time. It also reliably yields rapid visual acuity
      recovery without complications.

PMID- 27051260
TI  - Obstructive Sleep Apnea in Patients with Branch Retinal Vein Occlusion: A
      Preliminary Study.
AB  - PURPOSE: Our study aimed to determine whether obstructive sleep apnea (OSA) is
      common among branch retinal vein occlusion (BRVO) patients without systemic risk
      factors using a Watch PAT-100 portable monitoring device. METHODS: The study
      participants included consecutive patients with BRVO of less than 3 months
      duration without any risk factors known to be associated with OSA (diabetes,
      coronary artery disease, stroke, hematologic diseases, autoimmune disease, etc.)
      except for hypertension. All patients underwent full-night unattended
      polysomnography by means of a portable monitor Watch PAT-100 device. The apnea
      hypopnea index (AHI) was calculated as the average number of apnea and hypopnea
      events per hour of sleep, and an AHI score of five or more events was diagnosed
      as OSA. RESULTS: Among 19 patients (6 males and 13 females), 42.1% (8 of 19) had
      an AHI reflective of OSA. In the 13 patients who had no concurrent illness,
      including hypertension, 30.8% (4 of 13) had positive test results for OSA; three
      of these patients were ranked as mild OSA, while one had moderate OSA. The OSA
      group had an average AHI of 12.3 +/- 7.8, and the average AHI was 2.0 +/- 0.9 in
      the non-OSA group. Although it was not statistically proven, we found that OSA
      patients experienced a more severe form of BRVO. CONCLUSIONS: We found a higher
      than expected rate of OSA in BRVO patients lacking concomitant diseases typically
      associated with OSA. Our findings suggest that OSA could be an additional risk
      factor in the pathogenesis of BRVO or at least a frequently associated condition
      that could function as a triggering factor.

PMID- 27051259
TI  - Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Intravitreal
      Anti-vascular Endothelial Growth Factor Therapy.
AB  - PURPOSE: To determine the effects of intravitreal anti-vascular endothelial
      growth factor (VEGF) on thickness of the retinal nerve fiber layer (RNFL) in
      patients with age-related macular degeneration. METHODS: Twenty eyes of 20
      patients diagnosed with age-related macular degeneration who underwent
      intravitreal anti-VEGF injection were studied. Postinjection RNFL thickness was
      measured using optical coherence tomography. Average thickness, four-quadrant
      RNFL thicknesses, and intraocular pressure (IOP) in affected eyes were measured
      before and 6 and 12 months after anti-VEGF injection for comparison. RNFL
      thickness and IOP in affected and normal fellow eyes were also compared. Given
      that macular lesions can affect RNFL thickness, the changes in thickness were
      evaluated by dividing the 12 clock-hour RNFL into the pathologic areas adjacent
      to the lesion and the non-pathologic area. RESULTS: The mean clock-hour segment
      in the pathologic area was 4.8 hours. A significantly thicker RNFL was exhibited
      in temporal quadrants and pathologic areas (p = 0.043 and 0.048, respectively) in
      affected eyes before injection compared to the baseline RNFL thickness in normal
      eyes. No significant differences were found in RNFL thickness or IOP between
      affected and normal eyes after injection. The changes over time in the temporal
      and pathologic areas were statistically significant at 6 and 12 months after
      injection compared to baseline data (p < 0.05). No significant differences were
      displayed in RNFL thickness in the other three quadrants or in non-pathologic
      areas in either affected or normal eyes. Sequential changes in RNFL thickness in
      affected eyes were not significant. CONCLUSIONS: Repeat intravitreal anti-VEGF
      treatment did not have a significant effect on RNFL thickness. RNFL thickness
      significantly decreased with time in the pathologic areas and in the temporal
      segment adjacent to exudative macular lesions. The reduction in RNFL thickness
      was most likely associated with changes in the macular lesion rather than with
      anti-VEGF injection.

PMID- 27051261
TI  - Clinical Characteristics of Juvenile-onset Open Angle Glaucoma.
AB  - PURPOSE: To demonstrate the clinical characteristics of juvenile-onset open angle
      glaucoma (JOAG) and to evaluate the prognostic factors for visual field (VF)
      progression in eyes with JOAG. METHODS: The medical records of 125 eyes of 72
      patients with JOAG were analyzed retrospectively. At least four reliable VF tests
      were required to determine the VF progression, and the progression was defined
      using the modified Anderson criteria. Comparisons in clinical manifestations
      among groups were performed using independent t-test, and generalized estimating
      equations were also conducted. RESULTS: The mean follow-up duration was 94.4 +/-
      50.5 months. Patients with JOAG showed a male preponderance (64 %), myopia (-4.99
      +/- 4.01 diopters) and a severe elevation of intraocular pressure (35.6 +/- 10.8
      mmHg). Forty-two JOAG patients (58 %) had complained of symptoms associated with
      vision and pain; however, one-third presented with no definite symptoms. Fifty
      seven patients were diagnosed with JOAG in both eyes, and they were significantly
      older (p = 0.039) and had a greater family history (p = 0.035) than patients with
      unilateral JOAG. The progression group exhibited a significantly higher
      intraocular pressure at the last visit (p = 0.023) than the non-progression
      group. CONCLUSIONS: Because patients with considerable JOAG had no definite
      symptoms, periodic eye examinations are needed. To prevent the VF's progression,
      JOAG patients may require more careful management of intraocular pressure.

PMID- 27051262
TI  - Is Retinal Nerve Fiber Layer Thickness Change Related to Headache Lateralization
      in Migraine?
AB  - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in migraine
      patients with unilateral headache. METHODS: A total of 58 patients diagnosed with
      migraine headache consistently occurring on the same side and 58 age- and sex
      matched healthy subjects were evaluated in this cross-sectional study. RNFL
      thickness was measured using spectral-domain optical coherence tomography, and
      the side with the headache was compared with the contralateral side as well as
      with the results of healthy subjects. RESULTS: The mean patient age was 33.05 +/-
      8.83 years, and that of the healthy subjects was 31.44 +/- 8.64 years (p = 0.32).
      The mean duration of disease was 10.29 +/- 9.03 years. The average and nasal RNFL
      thicknesses were significantly thinner on the side of headache and on the
      contralateral side compared to control eyes (p < 0.05, for all). Thinning was
      higher on the side of the headache compared to the contralateral side; however,
      this difference was not statistically significant. CONCLUSIONS: The RNFL
      thicknesses were thinner on the side of the headache compared to the
      contralateral side in the migraine patients with unilateral headache, but this
      difference was not statistically significant.

PMID- 27051263
TI  - Retinal Nerve Fiber Layer Thickness Measurement Comparison Using Spectral Domain
      and Swept Source Optical Coherence Tomography.
AB  - PURPOSE: To investigate the retinal nerve fiber layer (RNFL) thickness
      concordance when measured by spectral domain (SD) and swept source (SS) optical
      coherence tomography (OCT), and to compare glaucoma-discriminating capability.
      METHODS: RNFL thicknesses were measured with the scan circle, centered on the
      optic nerve head, in 55 healthy, 41 glaucoma suspected, and 87 glaucomatous eyes.
      The RNFL thickness measured by the SD-OCT (sdRNFL thickness) and SS-OCT (ssRNFL
      thickness) were compared using the t-test. Bland-Altman analysis was performed to
      examine their agreement. We compared areas under the receiver operating
      characteristics curve and examined sdRNFL and ssRNFL thickness for discriminating
      glaucomatous eyes from healthy eyes, and from glaucoma suspect eyes. RESULTS: The
      average ssRNFL thickness was significantly greater than sdRNFL thickness in
      healthy (110.0 +/- 7.9 vs. 100.1 +/- 6.8 um, p < 0.001), glaucoma suspect (96.8
      +/- 9.3 vs. 89.6 +/- 7.9 um, p < 0.001), and glaucomatous eyes (74.3 +/- 14.2 vs.
      69.1 +/- 12.4 um, p = 0.011). Bland-Altman analysis showed that there was a
      tendency for the difference between ssRNFL and sdRNFL to increase in eyes with
      thicker RNFL. The area under the curves of the average sdRNFL and ssRNFL
      thickness for discriminating glaucomatous eyes from healthy eyes (0.984 vs.
      0.986, p = 0.491) and glaucoma suspect eyes (0.936 vs. 0.918, p = 0.132) were
      comparable. CONCLUSIONS: There was a tendency for ssRNFL thickness to increase,
      compared with sdRNFL thickness, in eyes with thicker RNFL. The ssRNFL thickness
      had comparable diagnostic capability compared with sdRNFL thickness for
      discriminating glaucomatous eyes from healthy eyes and glaucoma suspect eyes.

PMID- 27051264
TI  - Pseudoepitheliomatous Hyperplasia as a Limbal Mass Mimicking Nodular
      Episcleritis.

PMID- 27051265
TI  - Thermal Ocular Surface Injury from Cooking Oil: Delayed Onset Transient Corneal
      Infiltration and Myopic Shift.

PMID- 27051266
TI  - Early Retinal Changes in Hunter Syndrome According to Spectral Domain Optical
      Coherence Tomography.

PMID- 27051268
TI  - Correction.
AB  - [This corrects the article DOI: 10.15844/pedneurbriefs-29-8-3.]. 

PMID- 27051267
TI  - Macular Edema after Gabapentin.

PMID- 27051269
TI  - Comparison of visual outcomes after implantation of diffractive trifocal toric
      intraocular lens and a diffractive apodized bifocal toric intraocular lens.
AB  - PURPOSE: The aim of this study was to compare a new diffractive trifocal toric
      lens with an apodized diffractive bifocal toric lens in terms of refractive and
      visual acuity (VA) outcomes, including low-contrast VA (LCVA), as well as the
      patient's visual function 3 months after implantation. PATIENTS AND METHODS: This
      is a randomized prospective study involving bilateral implantation of a trifocal
      toric or a bifocal toric lens. At 3 months postoperatively, the subject's vision
      was tested both uncorrected and with his/her best distance correction at:
      distance (4 m), intermediate (63 cm), and near (40 cm). Binocular defocus curves
      were measured with no correction and with the subject's best distance correction
      in place. Quality of vision was measured using the National Eye Institute Visual
      Function Questionnaire. RESULTS: A total of 22 patients were enrolled (eleven in
      each group). There was no statistically significant difference in the absolute
      change in measured rotation between 1 month and 3 months postoperatively between
      the two intraocular lens (IOL) groups (P=0.98). At 3 months, the postoperative
      refraction and distance VA by eye were similar between groups. There was no
      statistically significant difference in the measured LCVA between groups
      (P=0.39). The defocus curve showed that at 67 cm, the trifocal toric lens had
      statistically significantly better VA when compared to the bifocal toric lens.
      There were no statistically significant differences by group for any of the
      National Eye Institute Visual Function Questionnaire scores (P>0.26 in all
      cases). CONCLUSION: The trifocal toric IOL improved the intermediate vision
      without negatively impacting visual function and distance, near, or low-contrast
      VA when compared to a bifocal toric IOL. The toric component of the trifocal lens
      effectively reduced astigmatism and provided good rotational stability.

PMID- 27051271
TI  - Normal corneal endothelial cell density in Nigerians.
AB  - AIM: The aim of the study was to describe the corneal endothelial cell density of
      adults at the MeCure Eye Center and to determine the relationship between age,
      sex, and corneal endothelial cell density. METHODS: This study was a
      retrospective study looking at those records of individuals who had undergone
      specular microscopy or corneal endothelial cell count measurement at the MeCure
      Eye Center. RESULTS: The endothelial cell characteristics of 359 healthy eyes of
      201 volunteers were studied. The mean corneal endothelial cell density (MCD) was
      2,610.26+/-371.87 cells/mm(2) (range, 1,484-3,571 cells/mm(2)). The MCD decreased
      from 2,860.70 cells/mm(2) in the 20-30-year age group to 2,493.06 cells/mm(2) in
      the >70-year age group, and there was a statistically significant relationship
      between age and MCD with a P-value of <0.001. There was no statistically
      significant correlation between sex and corneal endothelial cell density
      (P=0.45). CONCLUSION: This study shows that endothelial cell density in Nigerian
      eyes is less than that reported in the Japanese, American, and Chinese eyes, and
      is comparable to that seen in Indian and Malaysian eyes.

PMID- 27051272
TI  - Corneal biomechanics in asymmetrical normal-tension glaucoma.
AB  - PURPOSE: We aimed to assess corneal biomechanics using the ocular response
      analyzer in patients with normal-tension glaucoma (NTG), and to evaluate the
      relationship between corneal biomechanics and visual field loss. METHODS: This
      was a prospective observational case series including patients with bilateral
      asymmetric NTG. For all patients, corneal hysteresis (CH), corneal resistance
      factor (CRF), CH - CRF difference, and central corneal thickness values were
      matched against the mean deviation (MD) of the visual field and the cup/disc
      ratio. For paired-eye comparison in each patient, both eyes were categorized into
      a better-eyes group and a worse-eyes group according to lower and higher corneal
      compensated intraocular pressure readings, respectively. Statistical analysis was
      carried out with the independent-samples Student's t-test, and the level of
      statistical significance was set at 0.05. Correlation was assessed using
      Pearson's correlation coefficient. RESULTS: The study included 240 eyes of 120
      patients. CH was inversely proportional to the MD in the visual field (P=0.01).
      CRF in both eyes was inversely proportional to the MD of the visual field
      (P=0.01). CH - CRF difference was directly proportional to the MD of the visual
      field (P=0.01). For paired-eye comparison, lower corneal-compensated intraocular
      pressure was associated with higher CH, higher CRF, smaller cup/disc ratio, and
      less deterioration of MD of visual field. CONCLUSION: CH, CRF, and CH - CRF are
      more powerful predictors of NTG progression than central corneal thickness.

PMID- 27051270
TI  - Ocriplasmin: who is the best candidate?
AB  - Enzymatic vitreolysis is currently the focus of attention around the world for
      treating vitreomacular traction and full-thickness macular hole. Induction of
      posterior vitreous detachment is an active area of developmental clinical and
      basic research. Despite exerting an incompletely elucidated physiological effect,
      ocriplasmin (also known as microplasmin) has been recognized to serve as a well
      tolerated intravitreal injection for the treatment of vitreomacular traction and
      full-thickness macular hole. There are several unexplored areas of intervention
      where enzymatic vitreolysis could potentially be used (ie, diabetic macular
      edema). Recent promising studies have included combinations of enzymatic
      approaches and new synthetic molecules that induce complete posterior vitreous
      detachment as well as antiangiogenesis. Although no guidelines have been proposed
      for the use of ocriplasmin, this review attempts to aid physicians in answering
      the most important question, "Who is the best candidate?" 

PMID- 27051273
TI  - Effects of acute and chronic administration of neurosteroid
      dehydroepiandrosterone sulfate on neuronal excitability in mice.
AB  - BACKGROUND: Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been
      associated with important brain functions, including neuronal survival, memory,
      and behavior, showing therapeutic potential in various neuropsychiatric and
      cognitive disorders. However, the antagonistic effects of DHEAS on gamma-amino
      butyric acidA receptors and its facilitatory action on glutamatergic
      neurotransmission might lead to enhanced brain excitability and seizures and thus
      limit DHEAS therapeutic applications. The aim of this study was to investigate
      possible age and sex differences in the neuronal excitability of the mice
      following acute and chronic DHEAS administration. METHODS: DHEAS was administered
      intraperitoneally in male and female adult and old mice either acutely or
      repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the
      potential proconvulsant properties of DHEAS, we studied the effects of acute and
      chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D
      aspartate-induced seizures in mice. The effects of acute and chronic DHEAS
      administration on the locomotor activity, motor coordination, and body weight of
      the mice were also studied. We also investigated the effects of DHEAS treatment
      on [(3)H]flunitrazepam binding to the mouse brain membranes. RESULTS: DHEAS did
      not modify the locomotor activity, motor coordination, body weight, and brain
      [(3)H]flunitrazepam binding of male and female mice. The results failed to
      demonstrate significant effects of single- and long-term DHEAS treatment on the
      convulsive susceptibility in both adult and aged mice of both sexes. However,
      small but significant changes regarding sex differences in the susceptibility to
      seizures were observed following DHEAS administration to mice. CONCLUSION:
      Although our findings suggest that DHEAS treatment might be safe for various
      potential therapeutic applications in adult as well as in old age, they also
      support subtle interaction of DHEAS with male and female hormonal status, which
      may underline observed sex differences in the relationship between DHEAS and
      various health outcomes.

PMID- 27051274
TI  - Role of glycogen synthase kinase-3beta inhibitor AZD1080 in ovarian cancer.
AB  - BACKGROUND: Glycogen synthase kinase-3beta (GSK-3beta) is a multifunctional
      serine/threonine kinase that plays an important role in cancer tumorigenesis and
      progression. We investigated the role of the GSK-3beta inhibitor AZD1080 in
      ovarian cancer cell lines. METHODS: A2780 and OVCAR3 ovarian cancer cell lines
      were exposed to AZD1080, after which cell proliferation, cell cycle, invasion,
      and migration assays were performed. Phalloidin staining was used to observe
      lamellipodia formation. Reverse transcription polymerase chain reaction and
      Western blot were used to assess the respective mRNA and protein expression
      levels of GSK-3beta, CDK2, CDK1, cyclin D1, matrix metalloproteinase-9 (MMP9),
      and Bcl-xL. RESULTS: AZD1080 exposure suppressed ovarian cancer cell
      proliferation, invasion, migration, and lamellipodia formation, and induced G1
      arrest, which was concentration dependent. AZD1080 also significantly
      downregulated GSK-3beta, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at
      both mRNA and protein levels. CONCLUSION: Taken together, our results demonstrate
      that the GSK-3beta inhibitor AZD1080 suppresses ovarian cancer development and
      therefore may indicate a new direction for ovarian cancer treatment.

PMID- 27051275
TI  - Development and validation of a predictive model of failed stepping-down of
      inhaled corticosteroids in adult asthmatics.
AB  - BACKGROUND: Asthma guidelines suggest stepping-down of inhaled corticosteroids
      (ICSs) when asthma is stable. OBJECTIVE: To determine outcomes of stepping-down
      and prediction of outcome after stepping-down of ICSs in controlled adult asthma.
      METHODS: We performed a retrospective study on 21-81 year-old hospital-based
      outpatients with asthma in Japan. Protocol for stepping-down of ICSs was
      performed according to the GINA guideline. Failure/success of stepping-down is
      judged as occurring exacerbation or not for stepping-down of ICSs. Multiple
      logistic regression analysis was used to develop a prediction model for failed
      stepping-down, and then was validated by the leave-one-out cross-validation
      method. Our model of prediction score was calculated using receiver-operating
      characteristic area under the curve (AUC) analysis. The Nelson-Aalen curve
      demonstrated time to failure of stepping-down of ICSs. RESULTS: A total of 126
      patients with asthma attempted the stepping-down of ICSs according to the
      guideline. Of patients with follow-up, 97 (77.0%) of stepping-down attempts were
      successful. Using multivariate logistic regression analysis, comorbidity with
      rhinitis/rhinosinusitis and phlegm grade were independent predictors of failed
      stepping-down of ICSs, with odds ratios of 3.8 (95% confidence interval, 1.04
      13.3; P=0.04) and 1.3 (95% confidence interval, 1.01-11.5; P=0.04), respectively.
      These variables were then used to build a prediction score in terms of the
      prediction of failed stepping-down events. When the two variables were added to
      form the prediction score, the discriminative power of scores calculated by the
      prediction model using the AUC was 0.75 (range: 0.62-0.88) for naive prediction
      and 0.72 (range: 0.60-0.86) after cross-validation. In the time-to-failure
      models, cumulative hazard ratio of failed stepping-down have fixed 1 year after
      stepping-down. CONCLUSION: Our results suggest that comorbidity with
      rhinitis/rhinosinusitis and phlegm grade are imperative to predict failed
      stepping-down of ICSs in controlled patients with adult asthma.

PMID- 27051276
TI  - Sociodemographic factors affecting the quality of life of patients with asthma.
AB  - BACKGROUND: In recent years, there has been an increased interest in the
      subjective quality of life (QoL) of patients with bronchial asthma. Patients
      diagnosed with asthma experience a number of problems with regard to everyday
      activities and functions, which adversely affects their health-related QoL. AIM:
      The aim of this study is to analyze the sociodemographic factors affecting the
      QoL of patients with asthma. PATIENTS AND METHODS: The study comprised of 100
      patients (73 females and 27 males) aged 18-84 years (mean age 45.7 years) treated
      in the Department and Clinic of Internal Diseases, Geriatrics and Allergology,
      Wroclaw Medical University. All patients with asthma who met the inclusion
      criteria participated in the study. We used medical record analysis and two
      questionnaires: the asthma quality of life questionnaire (AQLQ) and the asthma
      control test. Up-to-date sociodemographic data were collected from all
      participants, including sex, age, marital status, education, and sources of
      income. RESULTS: The sociodemographic variables that correlated positively with
      QoL in all domains of the AQLQ were professional activity and higher education
      level of respondents. Factors that negatively influenced the AQLQ domains were
      older age and lack of professional activity. CONCLUSION: This study shows that
      age, physical work, and lack of professional activity decreased the QoL in this
      patient group. It was found that higher education contributes to better QoL
      scores.

PMID- 27051277
TI  - Preferences of color and lip position for facial attractiveness by laypersons and
      orthodontists.
AB  - BACKGROUND: Previous studies have reported some evaluation methods about
      profiles, but so far, they have no consistent agreement on the esthetic profiles
      of color images. Thus, the aim of this study was to determine whether the judges
      have different preferences about the color of the photograph and lip position for
      esthetic profiles when comparing a Chinese boy and girl. METHODS: The
      photographic records of a Chinese boy and girl with a good balanced profile were
      randomly selected. The images of the patients' profile were altered to produce
      silhouettes and black and white and color photographs (a total of six images).
      After evaluation by the judges, the best two photographs of the boy and girl were
      used to produce images of anterior-posterior lip positions with -6, -4, -2, 0,
      +2, +4, and +6 mm in relation to the esthetic plane, which was created by
      Ricketts. The judges were invited to enumerate the images in the order in which
      they considered the most attractive. RESULTS: The chromophotograph was chosen as
      the best way to express the facial profile in both the boy and girl. The profiles
      with a deviation of -4 mm in the boy and a deviation of -2 mm in the girl from
      line E were considered as the most attractive, and the image with a deviation of
      +6 mm from the normal line E was considered the least attractive. There were
      statistically significant differences between the preferences of the profiles of
      the boy and girl; the same results were recorded in the variables educational
      background and clinic role of the judges. CONCLUSION: The chromophotograph was
      considered as the best way to evaluate the esthetic profiles, and the judges
      preferred the boy with a concave profile than the concave profile of the girl.

PMID- 27051278
TI  - Applications and toxicity of graphene family nanomaterials and their composites.
AB  - Graphene has attracted much attention of scientific community due to its enormous
      potential in different fields, including medical sciences, agriculture, food
      safety, cancer research, and tissue engineering. The potential for widespread
      human exposure raises safety concerns about graphene and its derivatives,
      referred to as graphene family nanomaterials (GFNs). Due to their unique chemical
      and physical properties, graphene and its derivatives have found important places
      in their respective application fields, yet they are being found to have
      cytotoxic and genotoxic effects too. Since the discovery of graphene, a number of
      researches are being conducted to find out the toxic potential of GFNs to
      different cell and animal models, finding their suitability for being used in new
      and varied innovative fields. This paper presents a systematic review of the
      research done on GFNs and gives an insight into the mode and action of these
      nanosized moieties. The paper also emphasizes on the recent and up-to-date
      developments in research on GFNs and their nanocomposites for their toxic
      effects. 

PMID- 27051279
TI  - Anemia in the frail, elderly patient.
AB  - Anemia and frailty are two common findings in geriatric patients and have been
      shown to be associated with poor outcomes in this patient group. Recent studies
      have contributed to the growing evidence of a possible association with the age
      related chronic inflammatory status known as "inflammaging". These findings do
      not only give a better insight into the pathogenesis of anemia in frailty, but
      also offer new treatment options. The present article focuses on this assumed
      association between anemia, frailty, and inflammaging and summarizes current
      management options for anemia in frail patients. 

PMID- 27051280
TI  - Association of sustained virologic response with reduced progression to liver
      cirrhosis in elderly patients with chronic hepatitis C.
AB  - OBJECTIVE: We studied the effect of sustained virologic response (SVR) after
      treatment with pegylated-interferon (PEG-IFN) plus ribavirin on the development
      of liver cirrhosis in elderly patients with chronic hepatitis C (CHC). PATIENTS
      AND METHODS: This retrospective study enrolled 145 elderly CHC patients (aged
      >=65 years) who were treatment-naive and were treated with PEG-IFN plus ribavirin
      for 6 months between January 2005 and December 2011. Abdominal sonography was
      performed and liver biochemistry was studied at baseline, at the end of
      treatment, and every 3-6 months thereafter. The development of liver cirrhosis
      and related complications was evaluated at the follow-ups. The aspartate
      aminotransferase-to-platelet ratio index was used as a noninvasive maker for
      fibrosis. RESULTS: The mean patient age was 69.1+/-3.3 years, and the average
      follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1-12.3
      years). Ninety-five patients (65.5%) achieved SVR, and 26 (17.9%) discontinued
      treatment. Twenty-seven patients (18.6%) developed liver cirrhosis after
      treatment. Patients without SVR had significantly greater risk of liver cirrhosis
      than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312
      8.761, P=0.012). The difference in 3-year cumulative incidence of liver cirrhosis
      was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0-57.5, P=0.012)
      compared with those with SVR (10.4%, 95% CI: 3.1-17.7). There was a trend of a
      higher baseline aspartate aminotransferase-to-platelet ratio index score in
      patients who progressed to liver cirrhosis compared with those who did not
      progress (2.1+/-1.2 vs 1.6+/-1.3, P=0.055), but the difference failed to reach
      significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921-1.791, P=0.14).
      CONCLUSION: An SVR following PEG-IFN combination treatment can reduce the risk of
      liver cirrhosis in elderly CHC patients.

PMID- 27051281
TI  - Analgesic use among nursing homes residents, with and without dementia, in
      Poland.
AB  - Many age-associated diseases are accompanied by pain. There is no doubt that pain
      is underrecognized among elderly nursing home residents and the diagnosing of
      pain is a real challenge in subjects with dementia. The aim of the study was to
      characterize analgesic use among nursing home residents and to delineate the
      putative associations between pain management and cognitive functions of elderly
      persons. The study involved 392 subjects (males:females - 81:311) with a mean age
      of 83.6+/-5.9 years. The residents' medical files in relation to diagnoses and
      drug consumption were analyzed, and the screening of cognitive functions was
      performed using the Mini-Mental State Examination (MMSE). One hundred and
      thirteen residents (28.8%) received some analgesics. Among them 84 (21.4%) used
      them routinely, 25 (6.4%) - pro re nata (PRN) and four (1.0%) - both routinely
      and PRN. Non-opioid analgesics were taken routinely by 53 residents, weak opioids
      by nine subjects, and one person was receiving strong opioids. Additionally,
      three individuals were taking a combination preparation of tramadol and
      acetaminophen. The rate of subjects who were not receiving any pain treatment was
      higher in residents with MMSE between 0 and 9 points than in those with MMSE
      between 24 and 30 points (P=0.0151). Furthermore, ten residents (9.1%) with
      severe dementia were treated with analgesics PRN. The results of our study point
      to a remarkably low use of analgesics in nursing home residents in Poland and
      indicate a need to introduce pain evaluation and monitoring of drug treatment
      appropriateness as a standard procedure in the geriatric assessment in nursing
      homes. 

PMID- 27051282
TI  - Pharmacokinetics and safety of olodaterol administered with the Respimat Soft
      Mist inhaler in subjects with impaired hepatic or renal function.
AB  - PURPOSE: In two trials, the influences of hepatic and renal impairment on the
      pharmacokinetics of olodaterol, a novel long-acting inhaled beta2-agonist for
      treatment of COPD, were investigated. SUBJECTS AND METHODS: The first trial
      included eight subjects with mild hepatic function impairment (Child-Pugh A),
      eight subjects with moderate impairment (Child-Pugh B), and 16 matched healthy
      subjects with normal hepatic function. The second trial included eight subjects
      with severe renal impairment (creatinine clearance <30 mL.min(-1)) and 14 matched
      healthy subjects with normal renal function. Subjects received single doses of 20
      or 30 MUg olodaterol administered with the Respimat Soft Mist inhaler. RESULTS:
      Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90%
      confidence intervals of dose-normalized area under the plasma concentration-time
      curve from time zero to 4 hours (AUC0-4) for subjects with mild and moderate
      hepatic impairment compared to healthy subjects were 97% (75%-125%) and 105% (79%
      140%), respectively. Corresponding values for dose-normalized maximum
      concentration (C max) were 112% (84%-151%) (mild impairment) and 99% (73%-135%)
      (moderate impairment). The geometric mean ratio (90% confidence interval) of AUC0
      4 for subjects with severe renal impairment compared to healthy subjects was 135%
      (94%-195%), and for C max was 137% (84%-222%). There was no significant
      relationship between creatinine clearance and AUC0-4 or C max. Renal clearance of
      olodaterol was reduced to 20% of normal in severe renal impairment. CONCLUSION:
      Mild to moderate hepatic function impairment or severe renal function impairment
      did not result in a clinically relevant increase of olodaterol systemic exposure
      after a single inhaled dose.

PMID- 27051283
TI  - Inhalation errors due to device switch in patients with chronic obstructive
      pulmonary disease and asthma: critical health and economic issues.
AB  - BACKGROUND: Different inhalation devices are characterized by different
      techniques of use. The untrained switching of device in chronic obstructive
      pulmonary disease (COPD) and asthma patients may be associated with inadequate
      inhalation technique and, consequently, could lead to a reduction in adherence to
      treatment and limit control of the disease. The aim of this analysis was to
      estimate the potential economic impact related to errors in inhalation in
      patients switching device without adequate training. METHODS: An Italian real
      practice study conducted in patients affected by COPD and asthma has shown an
      increase in health care resource consumption associated with misuse of inhalers.
      Particularly, significantly higher rates of hospitalizations, emergency room
      visits (ER), and pharmacological treatments (steroids and antimicrobials) were
      observed. In this analysis, those differences in resource consumption were
      monetized considering the Italian National Health Service (INHS) perspective.
      RESULTS: Comparing a hypothetical cohort of 100 COPD patients with at least a
      critical error in inhalation vs 100 COPD patients without errors in inhalation, a
      yearly excess of 11.5 hospitalizations, 13 ER visits, 19.5 antimicrobial courses,
      and 47 corticosteroid courses for the first population were revealed. In the same
      way, considering 100 asthma patients with at least a critical error in inhalation
      vs 100 asthma patients without errors in inhalation, the first population is
      associated with a yearly excess of 19 hospitalizations, 26.5 ER visits, 4.5
      antimicrobial courses, and 21.5 corticosteroid courses. These differences in
      resource consumption could be associated with an increase in health care
      expenditure for INHS, due to inhalation errors, of ?23,444/yr in COPD and
      ?44,104/yr in asthma for the considered cohorts of 100 patients. CONCLUSION: This
      evaluation highlights that misuse of inhaler devices, due to inadequate training
      or nonconsented switch of inhaled medications, is associated with a decrease in
      disease control and an increase in health care resource consumption and costs.

PMID- 27051284
TI  - A novel dissolution media for testing drug release from a nanostructured
      polysaccharide-based colon specific drug delivery system: an approach to
      alternative colon media.
AB  - The aim of this study was to develop a novel microbially triggered and animal
      sparing dissolution method for testing of nanorough polysaccharide-based micron
      granules for colonic drug delivery. In this method, probiotic cultures of
      bacteria present in the colonic region were prepared and added to the dissolution
      media and compared with the performance of conventional dissolution methodologies
      (such as media with rat cecal and human fecal media). In this study, the
      predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species,
      Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and
      5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of
      probiotic culture was added to the dissolution media to test the drug release of
      polysaccharide-based formulations. A USP dissolution apparatus I/II using a
      gradient pH dissolution method was used to evaluate drug release from
      formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit
      FS30D coated 5-fluorouracil granules was assessed under gastric and small
      intestine conditions within a simulated colonic environment involving
      fermentation testing with the probiotic culture. The results with the probiotic
      system were comparable to those obtained from the rat cecal and human fecal-based
      fermentation model, thereby suggesting that a probiotic dissolution method can be
      successfully applied for drug release testing of any polysaccharide-based oral
      formulation meant for colonic delivery. As such, this study significantly adds to
      the nanostructured biomaterials' community by elucidating an easier assay for
      colonic drug delivery. 

PMID- 27051285
TI  - Molecular magnetic resonance imaging of activated hepatic stellate cells with
      ultrasmall superparamagnetic iron oxide targeting integrin alphavbeta3 for
      staging liver fibrosis in rat model.
AB  - PURPOSE: To evaluate the expression level of integrin alphavbeta3 on activated
      hepatic stellate cells (HSCs) at different stages of liver fibrosis induced by
      carbon tetrachloride (CCl4) in rat model and the feasibility to stage liver
      fibrosis by using molecular magnetic resonance imaging (MRI) with arginine
      glycine-aspartic acid (RGD) peptide modified ultrasmall superparamagnetic iron
      oxide nanoparticle (USPIO) specifically targeting integrin alphavbeta3. MATERIALS
      AND METHODS: All experiments received approval from our Institutional Animal Care
      and Use Committee. Thirty-six rats were randomly divided into three groups of 12
      subjects each, and intraperitoneally injected with CCl4 for either 3, 6, or 9
      weeks. Controls (n=10) received pure olive oil. The change in T2* relaxation rate
      (DeltaR2*) pre- and postintravenous administration of RGD-USPIO or naked USPIO
      was measured by 3.0T clinical MRI and compared by one-way analysis of variance or
      the Student's t-test. The relationship between expression level of integrin
      alphavbeta3 and liver fibrotic degree was evaluated by Spearman's ranked
      correlation. RESULTS: Activated HSCs were confirmed to be the main cell types
      expressing integrin alphavbeta3 during liver fibrogenesis. The protein level of
      integrin alphav and beta3 subunit expressed on activated HSCs was upregulated and
      correlated well with the progression of liver fibrosis (r=0.954, P<0.001;
      r=0.931, P<0.001, respectively). After injection of RGD-USPIO, there is
      significant difference in DeltaR2* among rats treated with 0, 3, 6, and 9 weeks
      of CCl4 (P<0.001). The accumulation of iron particles in fibrotic liver specimen
      is significantly greater for RGD-USPIO than naked USPIO after being injected with
      equal dose of iron. CONCLUSION: Molecular MRI of integrin alphavbeta3 expressed
      on activated HSCs by using RGD-USPIO may distinguish different liver fibrotic
      stages in CCl4 rat model and shows promising to noninvasively monitor the
      progression of the liver fibrosis and therapeutic response to antifibrotic
      treatment.

PMID- 27051286
TI  - Enhanced dissolution and oral absorption of tacrolimus by supersaturable self
      emulsifying drug delivery system.
AB  - A new Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft
      copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS)
      was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use
      of oil, surfactant, and cosurfactant. A high payload supersaturable system (S
      SEDDS) was prepared by incorporating Soluplus, as a precipitation inhibitor, to
      SEDDS consisting of Capmul MCM, Cremophor EL, and Transcutol
      (FK506:vehicle:Soluplus =1:15:1). In vitro dissolution profile and in vitro
      pharmacokinetic aspect of S-SEDDS in rats were comparatively evaluated with those
      of conventional SEDDS formulas containing four times greater content of vehicle
      components (FK506:vehicle =1:60). Both formulations formed spherical drug-loaded
      microemulsion <70 nm in size when in contact with aqueous medium. In an in vitro
      dissolution test in a nonsink condition, the amphiphilic polymer noticeably
      retarded drug precipitation and maintained >80% of accumulated dissolution rate
      for 24 hours, analogous to that from conventional SEDDS. Moreover,
      pharmacokinetic parameters of the maximum blood concentration and area under the
      curve from S-SEDDS formula in rats were not statistically different (P>0.05) than
      those of conventional SEDDS. The results suggest that the Soluplus-based
      supersaturable system can be an alternative to achieve a comparable in vitro
      dissolution profile and in vivo oral absorption with conventional SEDDS, with
      minimal use of vehicle ingredients. 

PMID- 27051287
TI  - Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug
      encapsulation stability and site-specific drug delivery against tumors.
AB  - Although the shortcomings of small molecular antitumor drugs were efficiently
      improved by being entrapped into nanosized vehicles, premature drug release and
      insufficient tumor targeting demand innovative approaches that boost the
      stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the
      use of the core cross-linking method to generate a micelle with enhanced drug
      encapsulation ability and sensitivity of drug release in tumor. This kind of
      micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve
      tumor accumulation in vivo. We designed and synthesized the core cross-linked
      micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the
      hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit,
      and disulfide bond as the cross-linker. CCM showed spherical shape with a
      diameter of 91.2 nm by the characterization of dynamic light scattering and
      transmission electron microscope. Attributed to the core cross-linking, drug
      loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better
      sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake
      and in vitro antitumor studies proved the enhanced endocytosis and better
      cytotoxicity of CCM-Cur against HeLa cells, which had a high level of
      glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur)
      further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed
      that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours
      after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation
      with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By
      combining cross-linking of the core with active tumor targeting of FA, we
      demonstrated a new and effective way to design nanocarriers for enhanced drug
      encapsulation, smart tumor responsiveness, and elevated tumor accumulation. 

PMID- 27051288
TI  - A prosocial online game for social cognition training in adolescents with high
      functioning autism: an fMRI study.
AB  - To help patients with autism spectrum disorder (ASD) improve their social skills,
      effective interventions and new treatment modalities are necessary. We
      hypothesized that a prosocial online game would improve social cognition in ASD
      adolescents, as assessed using metrics of social communication, facial
      recognition, and emotional words. Ten ASD adolescents underwent cognitive
      behavior therapy (CBT) using a prosocial online game (game-CBT), and ten ASD
      adolescents participated in an offline-CBT. At baseline and 6 weeks later, social
      communication quality, correct identification of emotional words and facial
      emoticons, and brain activity were assessed in both groups. Social communication
      quality and correct response rate of emotional words and facial emoticons
      improved in both groups over the course of the intervention, and there were no
      significant differences between groups. In response to the emotional words, the
      brain activity within the temporal and parietal cortices increased in the game
      CBT group, while the brain activity within cingulate and parietal cortices
      increased in the offline-CBT group. In addition, ASD adolescents in the game-CBT
      group showed increased brain activity within the right cingulate gyrus, left
      medial frontal gyrus, left cerebellum, left fusiform gyrus, left insular cortex,
      and sublobar area in response to facial emoticons. A prosocial online game
      designed for CBT was as effective as offline-CBT in ASD adolescents.
      Participation in the game especially increased social arousal and aided ASD
      adolescents in recognizing emotion. The therapy also helped participants more
      accurately consider associated environments in response to facial emotional
      stimulation. However, the online CBT was less effective than the offline-CBT at
      evoking emotions in response to emotional words. 

PMID- 27051289
TI  - Post-stroke bacteriuria among stroke patients attending a physiotherapy clinic in
      Ghana: a cross-sectional study.
AB  - BACKGROUND: Infections are known to be a major complication of stroke patients.
      In this study, we evaluated the risk of community-acquired bacteriuria among
      stroke patients, the associated factors, and the causative organisms. METHODS:
      This was a cross-sectional study involving 70 stroke patients and 83 age- and sex
      matched, apparently healthy controls. Urine specimens were collected from all the
      study subjects and were analyzed by standard microbiological methods. Demographic
      and clinical information was also collected from the study subjects. For stroke
      patients, the information collected also included stroke parameters, such as
      stroke duration, frequency, and subtype. RESULTS: Bacteriuria was significantly
      higher among stroke patients (24.3%, n=17) than among the control group (7.2%,
      n=6), with a relative risk of 3.36 (confidence interval [CI], 1.40-8.01,
      P=0.006). Among the control group, all six bacteriuria cases were asymptomatic,
      whereas the 17 stroke bacteriuria cases comprised 15 cases of asymptomatic
      bacteriuria and two cases of symptomatic bacteriuria. Female sex (OR, 3.40; CI,
      1.12-10.30; P=0.03) and presence of stroke (OR, 0.24; CI, 0.08-0.70; P=0.009)
      were significantly associated with bacteriuria. The etiology of bacteriuria was
      similar in both study groups, and coagulase-negative Staphylococcus spp. were the
      most predominant organisms isolated from both stroke patients (12.9%) and the
      control group (2.4%). CONCLUSION: Stroke patients in the study region have a
      significantly higher risk of community-acquired bacteriuria, which in most cases
      is asymptomatic. Community-acquired bacteriuria in stroke patients appears to
      have little or no relationship with clinical parameters of stroke such as stroke
      subtype, duration and frequency.

PMID- 27051290
TI  - Prevalence and correlates of coronary heart disease: first population-based study
      in Lebanon.
AB  - BACKGROUND: Lebanon is experiencing a growing epidemic of coronary heart diseases
      (CHDs), as most low- and middle-income countries currently are. However, this
      growth can be attenuated if effective preventive strategies are adopted. PURPOSE:
      To provide the first national population-based prevalence of CHD and to describe
      the profile of Lebanese adults with prevalent CHD. METHODS: We carried out a
      cross-sectional study using a multistage cluster sample across Lebanon. We
      interviewed residents aged 40 years and older using a questionnaire that captured
      the presence of CHDs and their risk factors (RFs). RESULTS: Our study showed that
      13.4% of the Lebanese population aged >=40 years suffer from a prevalent CHD. CHD
      seemed to appear more prematurely than in developed countries, and males seemed
      to be more subject to CHD than females until a certain age. CHD was associated
      with older age, male sex, a lower economic situation, hypercholesterolemia,
      hypertension, having a family history of premature cardiovascular diseases, and
      suffering from diabetes. However, smoking and waist circumference did not seem to
      have an independent effect on CHD, but rather an effect mediated by biological
      RFs. CONCLUSION: This is the first nationwide endeavor conducted in Lebanon to
      assess the prevalence of CHD. This study also confirms the relevance of the
      classic RFs of CHD and their applicability to the Lebanese population, thus
      allowing for prevention strategies.

PMID- 27051292
TI  - Association between sociodemographic characteristics of female community health
      volunteers and their knowledge and performance on maternal and child health
      services in rural Nepal.
AB  - BACKGROUND: Engaging community health volunteers and community health workers to
      provide maternal and child health (MCH) care services in resource-poor settings
      is one of the global and widely used concepts. Despite a great role of female
      community health volunteers (FCHVs) in MCH services in Nepal, few research
      studies have been performed in this area. Our research aimed to assess the
      knowledge and performance of FCHVs on MCH services associated with their
      sociodemographic characteristics. METHODS: A cross-sectional survey was conducted
      to assess the knowledge and performance on selected MCH services of FCHVs using
      structured questionnaire in 16 village development committees of Dhanusha
      district, Southern Terai, Nepal, from the first of January to the end of February
      of 2014. A total of 138 FCHVs were selected by using multistage random sampling
      technique. Logistic regression was employed to examine the association between
      selected sociodemographic characteristics and knowledge and performance on MCH
      services of FCHVs after adjusting for significant variables associated with
      knowledge and performance and within-cluster effect. RESULTS: Our findings
      demonstrated that sociodemographic characteristics were associated independently
      with good knowledge of FCHVs on MCH services: education level secondary and above
      (adjusted odds ratio [aOR] 5.2; 95% confidence interval [CI] 2.2-12.2); residing
      in Mother and Infant Research Activities, nongovernmental organization working
      area (aOR 3.7; 95% CI 1.5-8.8); and middle caste (aOR 3.3; 95% CI 1.0-10.3).
      Similarly, satisfactory performance of FCHVs significantly associated with MCH
      services were education level secondary and above (aOR 8.9; 95% CI 3.2-24.3) and
      residing in Mother and Infant Research Activities working areas (aOR 9.0; 95% CI
      3.5-22.6). CONCLUSION: The study recommends considering education level while
      recruiting rural FCHVs and capacity enhancement through additional training and
      development programs in collaboration with developmental partner.

PMID- 27051291
TI  - A clinical approach to obstructive sleep apnea as a risk factor for
      cardiovascular disease.
AB  - Obstructive sleep apnea (OSA) is associated with cardiovascular risk factors,
      cardiovascular diseases, and increased mortality. Epidemiological studies have
      established these associations, and there are now numerous experimental and
      clinical studies which have provided information on the possible underlying
      mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have
      been performed to demonstrate that treatment of OSA by continuous positive airway
      pressure (CPAP) has the potential to reverse or at least to attenuate not only
      OSA but also the adverse cardiovascular effects associated with OSA. However, no
      randomized studies have been performed to demonstrate that treatment of OSA by
      CPAP improves clinical outcomes in patients with cardiovascular risk factors
      and/or established cardiovascular disease and concomitant OSA. In the present
      review, we summarize the current knowledge on the role of OSA as a potential
      cardiovascular risk factor, the impact of OSA on cardiac function, the role of
      OSA as a modifier of the course of cardiovascular diseases such as coronary
      artery disease, atrial fibrillation, and heart failure, and the insights from
      studies evaluating the impact of CPAP therapy on the cardiovascular features
      associated with OSA.

PMID- 27051293
TI  - Decreased apolipoprotein A-I level indicates poor prognosis in extranodal natural
      killer/T-cell lymphoma, nasal type.
AB  - BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is
      an invasive lymphoid malignancy with unfavorable survival, for which a prognostic
      model has not yet been validated. We hypothesized that serum apolipoprotein A-I
      (ApoA-I) may serve as a novel prognostic marker for ENKTL. PATIENTS AND METHODS:
      A total of 236 newly diagnosed cases of ENKTL were analyzed retrospectively.
      RESULTS: The optimal cutoff value for the serum ApoA-I level was determined to be
      0.95 g/L. A total of 154 and 82 cases were assigned to the high and low ApoA-I
      groups, respectively. Patients in the low ApoA-I group tended to present with
      poorer clinical features, a lower complete remission rate (P=0.001), and poor
      median progression-free survival (P<0.001) and overall survival (P<0.001).
      Multivariate analysis using Cox model showed that the serum ApoA-I level was an
      independent prognostic marker of overall survival (P<0.001) and progression-free
      survival (P<0.001) for ENKTL patients. For cases in the low-risk group, as
      assessed by International Prognostic Index, Prognosis Index for peripheral T-cell
      lymphoma, unspecified, and Korean Prognostic Index, the serum ApoA-I level was
      able to differentiate cases with poor outcomes from cases with good outcomes.
      CONCLUSION: Our results showed that the baseline serum ApoA-I level was helpful
      for predicting ENKTL prognosis.

PMID- 27051294
TI  - miR-34b inhibits nasopharyngeal carcinoma cell proliferation by targeting
      ubiquitin-specific peptidase 22.
AB  - OBJECTIVES: This study aimed to investigate the precise role of miR-34b in
      nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The expression of miR-34b
      and transcription of ubiquitin-specific peptidase 22 (USP22) were examined using
      quantitative reverse transcription-polymerase chain reaction. Western blot
      analysis was used to measure the protein expression of USP22. A dualluciferase
      assay was used to investigate the interaction between miR-34b and USP22. Cell
      viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide assay. The cell cycle was analyzed by propidium iodide
      staining followed by flow cytometry analysis. RESULTS: miR-34b was significantly
      downregulated in NPC tissues and NPC cell lines. Overexpression of miR-34b in NPC
      SUNE-6-10B cells inhibited cell viability and proliferation. USP22 was highly
      expressed in NPC cells and promoted cell viability and proliferation. Restoration
      of USP22 expression could reverse the effect of miR-34b on NPC cell viability and
      proliferation. CONCLUSION: miR-34b acts as a tumor suppressor in NPC, which is
      mediated via repression of the oncogene USP22.

PMID- 27051296
TI  - Ubiquitin-specific protease 7 expression is a prognostic factor in epithelial
      ovarian cancer and correlates with lymph node metastasis.
AB  - OBJECTIVE: Ubiquitin-specific protease 7 (USP7) is a common target of
      herpesviruses and is important in the DNA damage response, which is also
      upregulated in several cancers, including prostate, colon, liver, and lung
      cancers. However, less is known about its expression in ovarian cancer tissues.
      The role of USP7 in epithelial ovarian cancer (EOC) has not yet been
      investigated. MATERIALS AND METHODS: We recruited 141 patients from Linyi
      People's Hospital between June 1999 and June 2013, all pathologically diagnosed
      with primary EOC. Their clinical data were collected, and the expression of USP7
      in the tumor tissues was determined using immunohistochemistry. The correlations
      between USP7 expression and the clinicopathological variables of patients with
      EOC were assessed using Spearman's rank correlation test. Kaplan-Meier analysis
      and Cox regression analysis were used to identify the prognosis value of USP7.
      The function of USP7 in the EOC cells was also detected in vitro. RESULTS: Among
      the 141 cases, USP7 expression was high in 59 EOC samples (41.8%), and was
      significantly correlated with lymphatic invasion; USP7 can act as independent
      prognostic indicator for the overall survival (OS) of EOC, and its high
      expression was associated with poor OS rate. The RNA inteference and
      overexpression assays indicated that USP7 can positively regulate the ovarian
      cell vitality and invasion process. CONCLUSION: Patients with EOC expressing high
      level of USP7 have worse OS compared with those with low USP7 expression. USP7
      may be involved in the proliferation and invasion of EOC cells, and USP7
      expression can serve as an independent predictor of EOC.

PMID- 27051295
TI  - Bioinformatics analysis of differentially expressed proteins in prostate cancer
      based on proteomics data.
AB  - We mined the literature for proteomics data to examine the occurrence and
      metastasis of prostate cancer (PCa) through a bioinformatics analysis. We divided
      the differentially expressed proteins (DEPs) into two groups: the group
      consisting of PCa and benign tissues (P&b) and the group presenting both high and
      low PCa metastatic tendencies (H&L). In the P&b group, we found 320 DEPs, 20 of
      which were reported more than three times, and DES was the most commonly
      reported. Among these DEPs, the expression levels of FGG, GSN, SERPINC1, TPM1,
      and TUBB4B have not yet been correlated with PCa. In the H&L group, we identified
      353 DEPs, 13 of which were reported more than three times. Among these DEPs, MDH2
      and MYH9 have not yet been correlated with PCa metastasis. We further confirmed
      that DES was differentially expressed between 30 cancer and 30 benign tissues. In
      addition, DEPs associated with protein transport, regulation of actin
      cytoskeleton, and the extracellular matrix (ECM)-receptor interaction pathway
      were prevalent in the H&L group and have not yet been studied in detail in this
      context. Proteins related to homeostasis, the wound-healing response, focal
      adhesions, and the complement and coagulation pathways were overrepresented in
      both groups. Our findings suggest that the repeatedly reported DEPs in the two
      groups may function as potential biomarkers for detecting PCa and predicting its
      aggressiveness. Furthermore, the implicated biological processes and signaling
      pathways may help elucidate the molecular mechanisms of PCa carcinogenesis and
      metastasis and provide new targets for clinical treatment. 

PMID- 27051297
TI  - The efficacy and safety of nivolumab in the treatment of advanced melanoma: a
      meta-analysis of clinical trials.
AB  - BACKGROUND: Nivolumab has become a therapeutic regimen for the treatment of
      patients with advanced melanoma. The goal of this study was to assess the
      efficacy and safety of nivolumab in patients with advanced melanoma. METHODS: A
      systematic search from January 2008 to August 2015 with "nivolumab" and "advanced
      melanoma" as search terms was performed for possible clinical trials. According
      to the hazard ratio and the 95% confidence interval (CI) for progression-free
      survival (PFS), rates of objective response, complete response, partial response,
      rates of toxic effects, and the efficacy and safety of nivolumab were assessed.
      Using the software Review Manager (version 5.3) a meta-analysis was performed.
      RESULTS: There were four trials with 1,910 patients included. Based on the four
      trials, the pooled hazard ratio of PFS was 0.53 (95% CI, 0.43-0.66; P<0.001). The
      pooled risk ratio for the objective response rate, complete response, and partial
      response was 2.98% (95% CI, 2.38%-3.73%; P<0.001), 3.71% (95% CI, 2.67%-5.14%;
      P<0.001), and 2.51% (95% CI, 2.12%-2.99%; P<0.001), respectively. Nivolumab plus
      ipilimumab therapy significantly increased the risk of grade 3/4 rash and
      fatigue. CONCLUSION: Nivolumab-based therapy prolonged PFS in treatment of
      advanced melanoma, with less adverse effects. Nivolumab appears to be a favorable
      treatment option as a novel, targeted anticancer agent, for patients with
      advanced melanoma.

PMID- 27051298
TI  - Pemetrexed had significantly better clinical efficacy in patients with stage IV
      lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based
      chemotherapy after developing resistance to the first-line gefitinib treatment.
AB  - BACKGROUND: Increased evidences show that epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors such as gefitinib could prolong progression-free
      survival (PFS) compared with cytotoxic chemotherapy for metastatic lung
      nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was
      served as the first-line therapy. However, acquired resistance is inevitable, but
      the salvage therapies are still unclear. PATIENTS AND METHODS: We designed a
      retrospective study of the salvage therapy and enrolled patients with stage IV
      lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to
      the first-line gefitinib in two university-affiliated hospitals in Taiwan during
      June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation,
      performance statuses, response rate, PFS2 (the PFS in salvage therapy), and
      overall survival (OS2, the OS in salvage therapy) were recorded. RESULTS: Two
      hundred and nine patients with mutated EGFR and who took gefitinib as first-line
      therapy were identified in the period, and a total of 98 patients who had been
      treated with salvage therapy with cytotoxic chemotherapy or erlotinib were
      eligible for this study. The overall response rate of second salvage therapy is
      13%, and none of them received erlotinib. Patients who received chemotherapy had
      a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0
      months, P=0.1417) but not in OS. Furthermore, patients who received platinum
      based doublet had a trend for better PFS2 and a significantly better OS2 than
      those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months,
      P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007). Analyses of the patients
      receiving platinum-based doublet showed that patients receiving pemetrexed had a
      significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083) and a trend for
      better OS2 than those without pemetrexed treatment. CONCLUSION: Pemetrexed-based
      platinum chemotherapy may be the most optimal therapy in acquired resistance to
      gefitinib. Further prospective randomized controlled study is needed urgently.

PMID- 27051299
TI  - Lipid-rich carcinoma of the breast that is strongly positive for estrogen
      receptor: a case report and literature review.
AB  - Lipid-rich carcinoma (LRC) of the breast is a rare breast cancer variant that
      accounts for <1% of all breast malignancies. It has been reported that LRCs are
      negative for estrogen receptor. Here, we report a case of LRC of the breast that
      was strongly positive for estrogen receptor and treated with endocrine adjuvant
      therapy. A 52-year-old postmenopausal female noticed a lump in her right breast
      by self-examination and presented to our hospital. Physical examination revealed
      an elastic 30 mm *20 mm hard mass in the upper medial part of her right breast.
      The findings obtained using ultrasonography, mammography, and contrast-enhanced
      magnetic resonance imaging suggested breast cancer. Core needle biopsy resulted
      in the diagnosis of invasive carcinoma. The patient underwent mastectomy and
      sentinel lymph node biopsy. Histopathologically, the tumor cells were abundant in
      foamy cytoplasm. Because the presence of marked cytoplasmic lipid droplets was
      confirmed by Sudan IV staining and electron microscopic examination of the tumor
      and the lipid droplets were negative for periodic acid-Schiff staining, the tumor
      was diagnosed as an LRC. Immunohistochemically, estrogen and progesterone
      receptors of the tumor were strongly positive, human epidermal growth factor
      receptor type 2 was negative, and the ratio of Ki-67-positive cells was ~30%.
      After surgery, the patient underwent combination chemotherapy with anthracycline,
      cyclophosphamide, and 5-fluorouracil, followed by docetaxel. Thereafter, the
      pateint was treated with letrozole and has remained well for 24 months with no
      signs of recurrence. 

PMID- 27051300
TI  - Upregulation of metastasis-associated gene 2 promotes cell proliferation and
      invasion in nasopharyngeal carcinoma.
AB  - AIMS: Metastasis-associated gene 2 (MTA2) is reported to play an important role
      in tumor progression, but little is known about the role of MTA2 in
      nasopharyngeal carcinoma (NPC). The aim of the study was to explore the
      expression and function of MTA2 in NPC. METHODS: Expression of MTA2 in NPC
      tissues and cell lines was detected by immunohistochemistry and Western blotting.
      Relationship between MTA2 expression and clinicopathological features was
      analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were
      established by transfection with plasmids encoding MTA2 cDNA and lentivirus
      mediated short hairpin RNA, respectively. Cell viability was determined by Cell
      Counting Kit-8 and colony formation assay. Cell migration ability was evaluated
      by wound healing and transwell invasion assay. The impact of MTA2 knockdown on
      growth and metastasis of CNE2 cells in vivo was determined by nude mouse
      xenograft models. Expression of several Akt pathway proteins was detected by
      Western blotting. RESULTS: MTA2 was upregulated in NPC tissues and three NPC cell
      lines detected (CNE1, CNE2, and HNE1). MTA2 expression was related to clinical
      stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted
      proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite
      effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis
      of CNE2 cells in vivo. MTA2 overexpression activated Akt and upregulated the
      expression of matrix metalloproteinase 7 and cyclin D1. CONCLUSION: We conclude
      that MTA2 acts as an oncogene in tumorigenesis of NPC. MTA2 may be a potential
      target for gene therapy in NPC.

PMID- 27051301
TI  - Tumor necrosis factor-308 polymorphism with the risk and prognosis of non-Hodgkin
      lymphomas: a meta-analysis study.
AB  - BACKGROUND: Tumor necrosis factor-308 (TNF-308) was implied to be associated with
      the development of non-Hodgkin lymphoma (NHL). The aim of this meta-analysis
      study was to investigate the association of TNF-308A polymorphism with the
      susceptibility to, and prognosis of, NHL. METHODS: PubMed, Web of Science,
      Elsevier, HighWire, Scopus, and Google Scholar were searched up to May 2015. The
      association of TNF-308 polymorphism with the risk of NHL and prognosis was
      assessed by odds ratio and hazard ratio, respectively. RESULTS: Overall, TNF
      308G>A polymorphism increased the risk of NHL, B-cell lymphomas (BCL), and T-cell
      lymphomas and decreased the risk of follicular lymphomas. In stratified analysis,
      increased risk of BCL and diffuse large B-cell lymphomas (DLBCL) were observed in
      Caucasians and population-based studies, whereas decreased risk of NHL, BCL, and
      DLBCL were detected in Asians and hospital-based studies. Furthermore, pooled
      results of 1,192 patients with NHL from five studies suggested that TNF-308A was
      correlated with shorter progression-free survival and overall survival in
      patients with NHL, BCL, and DLBCL. CONCLUSION: Current evidence indicated that
      TNF-308A polymorphism was significantly associated with the risk and prognosis of
      NHL. Future studies should further confirm these associations in other NHL
      subtypes and ethnicities.

PMID- 27051302
TI  - High expression of Sox10 correlates with tumor aggressiveness and poor prognosis
      in human nasopharyngeal carcinoma.
AB  - PURPOSE: The aim of the study was to detect the expression of Sox10 in human
      nasopharyngeal carcinoma (NPC) and investigate the relationship between its
      expression and the clinicopathological characteristics of NPC patients. PATIENTS
      AND METHODS: Tumor specimens (n=105) were retrospectively collected from patients
      with NPC diagnosed between 2004 and 2005 who presented at Hunan Cancer Hospital.
      Immunohistochemistry analyses were performed to characterize the expression of
      Sox10 in NPC. Kaplan-Meier survival and Cox regression analyses were employed to
      evaluate the prognosis of 105 NPC patients. RESULTS: The results showed that
      Sox10 was markedly overexpressed in human NPC tissues. Analysis of
      clinicopathological parameters showed that high Sox10 expression was
      significantly correlated with the clinical stage (P=0.032), T classification
      (P=0.034), and lymph node metastasis (P=0.03). Cox regression analyses further
      showed that Sox10 expression was an independent prognostic factor for overall
      survival (P=0.005). This is the first time Sox10 has shown its importance in
      predicting NPC progressiveness and survival outcomes. CONCLUSION: Sox10 serves as
      a potential biomarker for NPC patients. It may hopefully become a novel
      therapeutic target for NPC patients.

PMID- 27051303
TI  - Statin use and mortality of patients with prostate cancer: a meta-analysis.
AB  - OBJECTIVE: The aim of this meta-analysis was to investigate the effect of statin
      use on the mortality of patients with prostate cancer (PCa). METHODS: An
      electronic search of PubMed, Embase, and CENTRAL databases from inception to
      August 2015 was performed to find eligible studies. Articles investigating the
      association between statin use and mortality of PCa were identified. Pooled
      hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using
      random- or fixed-effects models. RESULTS: In total, 13 studies that enrolled
      100,536 participants were included in this meta-analysis. Results showed that
      prediagnostic statin use had a significantly lower risk of both all-cause
      mortality (ACM; HR, 0.56; 95% CI, 0.38-0.83) and PCa-specific mortality (PCSM;
      HR, 0.53; 95% CI, 0.36-0.77). Similarly, postdiagnostic statin use was correlated
      with reductions in both ACM (HR, 0.77; 95% CI, 0.69-0.87) and PCSM (HR, 0.64; 95%
      CI, 0.52-0.79). When stratified by primary treatment, postdiagnostic use of
      statins had a 0.4-fold lower risk of ACM in patients with PCa who were treated
      with local therapy; both pre- and postdiagnostic use of statins was correlated
      with a significantly lower risk of PCSM in patients who were treated with
      androgen deprivation therapy. CONCLUSION: Both pre- and postdiagnostic use of
      statins is associated with better overall survival and PCa-specific survival.
      This suggests a need for randomized controlled trials of statins in patients with
      PCa.

PMID- 27051305
TI  - Progesterone receptor loss identifies hormone receptor-positive and HER2-negative
      breast cancer subgroups at higher risk of relapse: a retrospective cohort study.
AB  - BACKGROUND: To assess the prognostic value of progesterone receptor (PR)
      expression in patients with hormone receptor-positive and human epidermal growth
      factor receptor 2 (HER2)-negative breast cancer subgroups. METHODS: A
      retrospective review of breast cancer patients who underwent mastectomy or breast
      conserving surgery between January 1998 and December 2007 was performed. The
      prognostic impact of PR status on disease-free survival (DFS) was analyzed.
      RESULTS: Of the 1,301 patients included in this study, the median follow-up time
      was 64 months, and the median age was 46 years. There were 18.4% of patients
      (n=219) with PR negative (PR-) cancer. Women with PR-breast cancer were more
      likely to be postmenopausal (P<0.001) and have pN3 stage (P=0.031) and Stage III
      (P=0.049) cancer. Cox regression univariate and multivariate analysis showed that
      PR status was a significant prognostic factor for DFS. Patients with PR- status
      had poorer DFS (hazard ratio =1.626, 95% confidence interval =1.060-2.497,
      P=0.026). The 5-year DFS for patients with PR- and PR+ breast cancer was 79.4%
      and 86.2%, respectively, and the 8-year DFS for patients with PR- and PR+ breast
      cancer was 69.6% and 78.1%, respectively (P=0.012). A significant difference in
      DFS was observed between PR- and PR+ disease in patients with node-negative
      cancer, but was not for patients with lymph node metastasis (P=0.242). In
      premenopausal patients, DFS varied significantly by PR status (P=0.049). A
      marginally significant difference in DFS between the PR- and PR+ disease was seen
      in postmenopausal patients (log rank P=0.065). CONCLUSION: Lack of PR expression
      is associated with worse survival in patients with hormone receptor-positive and
      HER2-negative breast cancer subgroups.

PMID- 27051304
TI  - Up-regulated expression of phospholipase C, beta1 is associated with tumor cell
      proliferation and poor prognosis in hepatocellular carcinoma.
AB  - BACKGROUND: Phospholipase C, beta1 (PLCB1) plays critical roles in intracellular
      transduction and regulating signal activation which are important to
      tumorigenesis. However, the mechanism of PLCB1 in hepatocellular carcinoma (HCC)
      is still unknown. This study aims to investigate whether its expression is
      associated with the clinicopathological parameters and prognosis of the patients
      with HCC. METHODS: Immunohistochemistry on two tissue microarrays containing 141
      cases of HCC tissues and adjacent non-tumorous tissues were performed to analyze
      the correlation between PLCB1 expression and clinicopathological features. Kaplan
      Meier analysis and Cox multivariate analysis were performed to determine the
      PLCB1 expression in HCC prognosis. Furthermore, effects of PLCB1 on proliferation
      of HCC cells were explored using a colony formation assay and apoptosis assay.
      RESULTS: We identified that PLCB1 expression was significantly higher in tumor
      tissues than that in adjacent non-tumorous tissues and associated with advanced
      tumor stage. Kaplan-Meier survival analysis showed that patients with PLCB1
      positive tumors had poorer survival than the patients with PLCB1-negative tumors.
      In multivariate analyses, PLCB1 expression was an independent prognostic factor.
      Moreover, overexpression of PLCB1 in HCC cells promoted cell proliferation and
      inhibited apoptosis, while knocking down PLCB1 reduced cell viability in vitro.
      Further investigation found that activation of ERK signaling might involve in
      PLCB1-mediated cell growth. CONCLUSION: Our study suggests that PLCB1 promotes
      the progression of HCC and can be served as an independent prognostic factor and
      a promising therapeutic target in HCC.

PMID- 27051306
TI  - The interleukin-18 gene promoter -607 A/C polymorphism contributes to non-small
      cell lung cancer risk in a Chinese population.
AB  - The purpose of the present study was to determine the relationship between
      interleukin-18 (IL-18) -607 A/C polymorphism and the risk of non-small-cell lung
      cancer (NSCLC) and its impact on the serum IL-18 level. The genotyping of IL-18 
      607 A/C polymorphism was detected by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). The results showed that the AA/AC
      genotype distribution in NSCLC patients was significantly higher than that of
      healthy controls (P=0.02). However, no significant differences were found between
      the two subgroups when stratified by clinical characteristics. Furthermore, serum
      IL-18 levels were found to be significantly higher in the NSCLC patients than in
      the controls (P=0.01) as detected by enzyme-linked immunosorbent assay analysis.
      There was no correlation between serum IL-18 levels and different genotypes. In
      conclusion, these findings suggest that IL-18 -607 A/C polymorphism increases the
      risk of NSCLC in the Chinese population, and this polymorphism could not
      functionally affect the IL-18 levels. 

PMID- 27051307
TI  - Clinicopathological significance of STAT4 in hepatocellular carcinoma and its
      effect on cell growth and apoptosis.
AB  - BACKGROUND: Recent studies showed that signal transducer and activator of
      transcription 4 (STAT4) was downregulated in hepatocellular carcinoma (HCC)
      tissues. However, the role of STAT4 in HCC is still unknown. The aim of this
      study is to explore the association between STAT4 expression and other
      clinicopathological features in HCC and to test the effect of STAT4 on cell
      growth and apoptosis in vitro. METHODS: STAT4 was evaluated by
      immunohistochemistry in 171 HCC and corresponding paraneoplastic liver, 37
      cirrhosis, and 33 normal liver tissues. Association between STAT4 and
      clinicopathological parameters was analyzed. Meta-analysis on STAT4 in cancer was
      performed. The effect of STAT4 small interfering RNA (siRNA) on cell growth and
      cell apoptosis was also detected. RESULTS: Positive rate of STAT4 was 29.2%
      (50/171) in HCC tissues, 53.2% (91/171) in paraneoplastic liver tissues, 64.9%
      (24/37) in cirrhosis tissues, and 72.7% (24/33) in normal liver tissues. STAT4
      was upregulated in younger patients who were female, with single tumor node,
      early TNM stage, without portal vein tumor embolus, and alpha-fetoprotein (AFP)
      positive tumors compared with the groups comprising older patients, males, and
      those with multiple tumor nodes, advanced TNM stage, with portal vein tumor
      embolus, and AFP negative tumors. Meta-analysis showed STAT4 was correlated with
      TNM stage (OR =0.50, 95% CI =0.30, 0.83, P=0.008) and age (OR =0.58, 95% CI
      =0.38, 0.95, P=0.032) in malignant tissues, and with AFP level (OR =1.76, 95% CI
      =1.06, 2.94, P=0.03) in HCC. STAT4 siRNA promoted growth and suppressed apoptosis
      of HepG2 cells. CONCLUSION: STAT4 might play a vital role in development of HCC,
      via influencing cell growth and apoptosis, as a tumor suppressor.

PMID- 27051308
TI  - Challenges in the management of severe allergic asthma in the elderly.
AB  - Little is known about the features of asthma and allergy in the elderly. A
      significant number of elderly patients with asthma have uncontrolled and severe
      asthma. This review aims to provide an analysis of the literature on the
      assessment and phenotype of severe allergic asthma in the elderly. Gaps and
      pitfalls in diagnostic and therapeutic approaches, as well as management of
      severe allergic asthma in the elderly, are also discussed. 

PMID- 27051309
TI  - Step-down therapy in well-controlled asthmatic patients using salmeterol
      xinafoate/fluticasone propionate combination therapy.
AB  - PURPOSE: A combination therapy with inhaled corticosteroid (ICS) and a long
      acting beta agonist (LABA) is the standard treatment for asthmatic patients, and
      step-down treatment is recommended once control has been achieved. However,
      little data exist that evaluate the long-term outcomes after step-down treatment.
      OBJECTIVE: To compare the long-term outcomes of step-down therapy with ICS/LABA
      or ICS alone for asthmatic patients who have achieved well-controlled asthma by
      the ICS (250 ug fluticasone)/LABA (50 ug salmeterol) combination (SFC, two puffs
      per day). PATIENTS AND METHODS: We randomized 40 well-controlled patients with
      asthma receiving SFC (250 ug) to two groups; one group of patients received step
      down therapy with low-dose SFC (100 ug, two puffs daily) and another group of
      patients received step-down therapy with high-dose fluticasone propionate (FP)
      alone (500 ug, daily). The two groups were monitored over 12 months for changes
      in asthma control test scores, respiratory function (percent forced expiratory
      volume in 1 second, maximal expiratory flow rate at 50% of the vital capacity
      [%FEF50], and maximal expiratory flow rate at 25% of the vital capacity
      [%FEF25]), and the concentration of fractional exhaled nitric oxide. RESULTS:
      There was no significant difference in the dropout rate between the SFC and FP
      groups. Low-dose SFC maintained the stability of all parameters over 12 months,
      whereas the FP group exhibited a rapid 5% decrease in forced expiratory volume in
      1 second within 2 months after discontinuation of salmeterol; furthermore, after
      10 months, there was a gradual decrease in %FEF50 and %FEF25. CONCLUSION: This
      study suggests that a balanced step-down protocol, including both ICS and LABA,
      is essential in providing long-term stability to patients with mild-to-moderate
      well-controlled asthma.

PMID- 27051310
TI  - Lifestyle Intervention for Weight Loss: a group-based program for Emiratis in
      Ajman, United Arab Emirates.
AB  - BACKGROUND: Lifestyle Intervention for Weight Loss (LIFE-8) is developed as a
      structured, group-based weight management program for Emiratis with obesity and
      type 2 diabetes. It is a 3-month program followed by a 1-year follow-up. The
      results from the first 2 years are presented here to indicate the possibility of
      its further adaptation and implementation in this region. METHODOLOGY: We
      recruited 45 participants with obesity and/or type 2 diabetes based on
      inclusion/exclusion criteria. The LIFE-8 program was executed by incorporating
      dietary modification, physical activity, and behavioral therapy, aiming to
      achieve up to 5% weight loss. The outcomes included body weight, fat mass, waist
      circumference, blood pressure, fasting blood glucose (FBG), hemoglobin A1c
      (HbA1c), and nutritional knowledge at 3 months and 12 months. RESULTS: We
      observed a reduction of 5.0% in body weight (4.8+/-2.8 kg; 95% CI 3.7-5.8), fat
      mass (-7.8%, P<0.01), and waist circumference (Delta=4+/-4 cm, P<0.01) in the
      completed participants (n=28). An improvement (P<0.05) in HbA1c (7.1%+/-1.0% vs
      6.6%+/-0.7%) and FBG (8.2+/-2.0 mmol/L vs 6.8+/-0.8 mmol/L) was observed in
      participants with obesity and type 2 diabetes after the program. Increase in
      nutritional knowledge (<0.01) and overall evaluation of the program (9/10) was
      favorable. On 1-year follow-up, we found that the participants could sustain
      weight loss (-4.0%), while obese, type 2 diabetic participants sustained HbA1c
      (6.6%+/-0.7% vs 6.4%+/-0.7%) and further improved (P<0.05) the level of FBG
      (6.8+/-0.8 mmol/L vs 6.7+/-0.4 mmol/L). CONCLUSION: LIFE-8 could be an effective,
      affordable, acceptable, and adaptable lifestyle intervention program for the
      prevention and management of diabetes in Emiratis. It was successful not only in
      delivering a modest weight loss but also in improving glycemic control in
      diabetic participants.

PMID- 27051311
TI  - New developments in the treatment of rosacea - role of once-daily ivermectin
      cream.
AB  - Rosacea is a chronic dermatological disorder with a variety of clinical
      manifestations localized largely to the central face. The unclear etiology of
      rosacea fosters therapeutic difficulty; however, subtle clinical improvement with
      pharmacologic treatments of various drug categories suggests a multifactorial
      etiology of the disease. Factors that may contribute to disease pathogenesis
      include immune abnormality, vascular abnormality, neurogenic dysregulation,
      presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction.
      The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory
      and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin
      and metronidazole, ivermectin was more effective; this treatment modality boasted
      more improved quality of life, reduced lesion counts, and more favorable
      participant and physician assessment of disease severity. Patients who received
      ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious
      in decreasing inflammatory lesion counts and erythema. 

PMID- 27051312
TI  - Familial Mediterranean fever: current perspectives.
AB  - Familial Mediterranean fever (FMF) is the most frequent monogenic
      autoinflammatory disease, and it is characterized by recurrent attacks of fever
      and polyserositis. The disease is associated with mutations in the MEFV gene
      encoding pyrin, which causes exaggerated inflammatory response through
      uncontrolled production of interleukin 1. The major long-term complication of FMF
      is amyloidosis. Colchicine remains the principle therapy, and the aim of
      treatment is to prevent acute attacks and the consequences of chronic
      inflammation. With the evolution in the concepts about the etiopathogenesis and
      genetics of the disease, we have understood that FMF is more complicated than an
      ordinary autosomal recessive monogenic disorder. Recently, recommendation sets
      have been generated for interpretation of genetic testing and genetic diagnosis
      of FMF. Here, we have reviewed the current perspectives in FMF in light of recent
      recommendations. 

PMID- 27051313
TI  - Effectiveness of continuous positive airway pressure in lowering blood pressure
      in patients with obstructive sleep apnea: a critical review of the literature.
AB  - Obstructive sleep apnea (OSA) is an extremely common comorbid condition in
      patients with hypertension, with a prevalence of ~50%. There is growing evidence
      suggesting that OSA is a secondary cause of hypertension, associated with both
      poor blood pressure (BP) control and target organ damage in patients with
      hypertension. The application of continuous positive airway pressure (CPAP)
      during sleep is the gold standard treatment of moderate- to-severe OSA and very
      effective in abolishing obstructive respiratory events. However, several meta
      analyses showed that the overall impact of CPAP on BP is modest (~2 mmHg). There
      are several potential reasons for this disappointing finding, including the
      heterogeneity of patients studied (normotensive patients, controlled, and
      uncontrolled patients with hypertension), non-ideal CPAP compliance, clinical
      presentation (there is some evidence that the positive impact of CPAP on lowering
      BP is more evident in sleepy patients), and the multifactorial nature of
      hypertension. In this review, we performed a critical analysis of the literature
      evaluating the impact of CPAP on BP in several subgroups of patients. We finally
      discussed perspectives in this important research area, including the urgent need
      to identify predictors of BP response to CPAP and the importance of precision
      medicine in this scenario. 

PMID- 27051314
TI  - Evaluation and treatment of hypertensive crises in children.
AB  - Hypertensive crises in children are medical emergencies that must be identified,
      evaluated, and treated promptly and appropriately to prevent end-organ injury and
      even death. Treatment in the acute setting typically includes continuous
      intravenous antihypertensive medications with monitoring in the intensive care
      unit setting. Medications commonly used to treat severe hypertension have been
      poorly studied in children. Dosing guidelines are available, although few
      pediatric-specific trials have been conducted to facilitate evidence-based
      therapy. Regardless of what medication is used, blood pressure should be lowered
      gradually to allow for accommodation of autoregulatory mechanisms and to prevent
      cerebral ischemia. Determining the underlying cause of the blood pressure
      elevation may be helpful in guiding therapy. 

PMID- 27051315
TI  - Factors affecting local recurrence and distant metastases of invasive breast
      cancer after breast-conserving surgery in Chiang Mai University Hospital.
AB  - BACKGROUND: The purpose of this study was to collect data regarding breast cancer
      profiles and factors that affect local recurrence and distant metastasis after
      breast-conserving surgery (BCS) in Chiang Mai University Hospital. MATERIALS AND
      METHODS: This study was a retrospective review in a single institution of newly
      diagnosed invasive breast cancer patients who were treated with BCS between April
      9, 2001 and December 25, 2011. RESULTS: A total of 185 patients treated with BCS
      were included in this study, with an average age of 46.83 years. The average
      recurrence age was 41.1 years and the average nonrecurrence age was 47.48 years,
      with a recurrence rate of 10.27%. Premenopause was significant in recurrence
      (P=0.047), as well as non-estrogen-expression patients (P=0.001) and patients who
      did not receive antihormonal treatment (P=0.011). CONCLUSION: The recurrence rate
      in our institute was 10.27%. Factors affecting recurrence after BCS included
      young age, premenopausal status, nonexpression of the estrogen receptor, and
      patients who had not received antihormonal treatment. The recurrence rate was
      higher in the first 90 postoperative months.

PMID- 27051316
TI  - Treatment outcomes of HIV-positive patients on first-line antiretroviral therapy
      in private versus public HIV clinics in Johannesburg, South Africa.
AB  - BACKGROUND: Despite the widely documented success of antiretroviral therapy
      (ART), stakeholders continue to face the challenges of poor HIV treatment
      outcomes. While many studies have investigated patient-level causes of poor
      treatment outcomes, data on the effect of health systems on ART outcomes are
      scarce. OBJECTIVE: We compare treatment outcomes among patients receiving HIV
      care and treatment at a public and private HIV clinic in Johannesburg, South
      Africa. PATIENTS AND METHODS: This was a retrospective cohort analysis of ART
      naive adults (>=18.0 years), initiating ART at a public or private clinic in
      Johannesburg between July 01, 2007 and December 31, 2012. Cox proportional
      hazards regression was used to identify baseline predictors of mortality and loss
      to follow-up (>3 months late for the last scheduled visit). Generalized
      estimating equations were used to determine predictors of failure to suppress
      viral load (>=400 copies/mL) while the Wilcoxon rank-sum test was used to compare
      the median absolute change in CD4 count from baseline to 12 months post-ART
      initiation. RESULTS: 12,865 patients initiated ART at the public clinic compared
      to 610 at the private clinic. The patients were similar in terms of sex and age
      at initiation. Compared to public clinic patients, private clinic patients
      initiated ART at higher median CD4 counts (159 vs 113 cells/mm(3)) and World
      Health Organization stage I/II (76.1% vs 58.5%). Adjusted hazard models showed
      that compared to public clinic patients, private clinic patients were less likely
      to die (adjusted hazard ratio [aHR] 0.50; 95% confidence interval [CI] 0.35-0.70)
      but were at increased risk of loss to follow-up (aHR 1.80; 95% CI 1.59-2.03). By
      12 months post-ART initiation, private clinic patients were less likely to have a
      detectable viral load (adjusted relative risk 0.65; 95% CI 0.49-0.88) and
      recorded higher median CD4 change from baseline (184 cells/mm(3) interquartile
      range 101-300 vs 158 cells/mm(3) interquartile range 91-244), when compared to
      public clinic patients. CONCLUSION: We identified differences in treatment
      outcomes between the two HIV clinics. Findings suggest that the type of clinic at
      which ART patients initiate and receive treatment can have an impact on treatment
      outcomes. Further research is necessary to provide more conclusive results.

PMID- 27051317
TI  - Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer:
      current perspectives.
AB  - Patients with platinum-resistant ovarian cancer have progression of disease
      within 6 months of completing platinum-based chemotherapy. While several
      chemotherapeutic options exist for the treatment of platinum-resistant ovarian
      cancer, the overall response to any of these therapies is ~10%, with a median
      progression-free survival of 3-4 months and a median overall survival of 9-12
      months. Bevacizumab (Avastin), a humanized, monoclonal antivascular endothelial
      growth factor antibody, has demonstrated antitumor activity in the platinum
      resistant setting and was recently approved by US Food and Drug Administration
      for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin,
      or topotecan. This review summarizes key clinical trials investigating
      bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an
      overview of efficacy, safety, and quality of life data relevant in this setting.
      While bevacizumab is currently the most studied and clinically available
      antiangiogenic therapy, we summarize recent studies highlighting novel
      alternatives, including vascular endothelial growth factor-trap, tyrosine kinase
      inhibitors, and angiopoietin inhibitor trebananib, and discuss their application
      for the treatment of platinum-resistant ovarian cancer. 

PMID- 27051318
TI  - Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome
      case.
AB  - Thalidomide may be used as a treatment option for pyoderma gangrenosum (PG) and
      myelodysplastic syndrome (MDS). Herein, we aimed to report a patient who was
      treated well with thalidomide and whose diagnosis was PG with MDS. A 61-year-old
      man with painless ecchymotic lesions in his right upper extremity was admitted to
      the hospital in Isparta, Turkey, in January 2015. The lesions were diagnosed as
      PG. In his anamnesis, it was found that he was diagnosed with MDS 6 years ago and
      had been treated with cyclosporine at 2*100 mg for 5 years, which was stopped in
      January 2015. Aspiration from liver lesion revealed the presence of Mycobacterium
      tuberculosis, so antituberculosis treatment was started. Bone marrow
      investigation revealed MDS-refractory anemia with excess blasts (7%). For lesions
      in bilateral upper extremities, thalidomide treatment was started at 50 mg/d.
      After 1 month from the initiation of thalidomide treatment, the lesions in upper
      extremities had disappeared. In the literature, there are some reports of
      patients with PG who were successfully treated with thalidomide. Our patient is a
      complicated case who simultaneously has MDS, PG, and tuberculosis infection. The
      reason for thalidomide usage in our patient was the need of immune modulation
      without immune suppression. Our patient has tolerated the drug well, and
      excellent response was obtained after 1 month of initiation of thalidomide
      treatment. To conclude, thalidomide is a very effective drug acting as an immune
      modulator, which is useful in the clinical management of both MDS and PG. 

PMID- 27051319
TI  - Childhood neuroblastoma masquerading as pheochromocytoma: case report.
AB  - Neuroblastoma is the most common extracranial solid tumor in children. Mild
      hypertension is a frequent symptom, presumably an effect of catecholamines that
      tumors release. Reported herein is the rare occurrence of severe hypertension and
      subsequent heart failure attributable to adrenal gland neuroblastoma. A 3-year
      old boy presented with anterior chest wall protrusion. Physical examination
      revealed severe hypertension, and left-sided cardiac failure was evident by
      echocardiography. Catecholamine metabolite (norepinephrine) levels were increased
      in serum (>2,000 pg/mL) and in urine (1,350.5 ug/day). Abdominal computed
      tomography scan showed a 7 cm solid mass arising from right adrenal gland. Oral
      phenoxybenzamine was given for hemodynamic stabilization, and right adrenalectomy
      was performed to remove an apparent pheochromocytoma. Ultimately, the pathologic
      diagnosis was ganglioneuroblastoma. Both hypertension and cardiac failure
      resolved postoperatively. 

PMID- 27051320
TI  - Gold shunt for refractory advanced low-tension glaucoma with spared central
      acuity.
AB  - The aim of this study is to report a case of gold shunt surgery for uncontrolled,
      low-tension glaucoma with good central vision, after having a previously failed
      trabeculectomy and tube shunt surgeries. The patient was receiving maximum
      medical glaucoma therapy of four different types with intraocular pressure of 17
      mm Hg prior to gold shunt surgery. Five years later, intraocular pressure is well
      controlled in the low teens without the need for ocular medications, and glaucoma
      is stable following gold shunt surgery. 

PMID- 27051321
TI  - A rare case of anastomosis between the external and internal jugular veins.
AB  - Jugular veins bring deoxygenated blood from the head back to the heart. There are
      two sets of external and internal veins. The external jugular vein receives the
      greater part of the blood from the cranium and the deep parts of the face. It
      commences from the substance of the parotid gland and runs down the neck at the
      posterior border of sternocleidomastoideus and ends in the subclavian vein in
      front of the scalenus anterior. The external jugular vein is covered by the
      platysma and its upper half runs parallel with the great auricular nerve. There
      is also another minor jugular vein, the anterior, draining the submaxillary
      region. In our patient, we recognized a shunt between the external and internal
      jugular veins. It appeared in the middle of the veins, between the pair of
      valves, which are placed ~2.5 cm above the termination of the vessel. The
      anastomosis was fully functional, and there was no problem in the blood pressure
      of the patient. Moreover, the shunt was not associated with any systemic disease.

PMID- 27051322
TI  - Drug diffusion and biological responses of arteries using a drug-eluting stent
      with nonuniform coating.
AB  - The purpose of this study was to determine the effect of a nonuniform coating,
      abluminal-gradient coating (AGC), which leaves the abluminal surface of the
      curves and links parts of the stent free from the drug coating, on the diffusion
      direction of the drug and the biological responses of the artery to drug-eluting
      stent (DES) by comparing the AGC-sirolimus stent and the conventional full
      surface coating (CFC) sirolimus stent. The study aimed to verify whether the AGC
      approach was appropriate for the development of a safer DES, minimizing the risks
      of stent thrombosis due to delayed endothelialization by the drug and distal
      embolization due to cracking of the coating layer on the hinge parts of the DES
      on stent expansion. In the in vitro local drug diffusion study, we used rhodamine
      B as a model drug, and rhodamine B released from the AGC stent diffused
      predominantly into the abluminal side of the alginate artery model. Conversely,
      rhodamine B released from the CFC stent quickly spread to the luminal side of the
      artery model, where endothelial cell regeneration is required. In the biological
      responses study, the luminal surface of the iliac artery implanted with the AGC
      sirolimus stent in a rabbit iliac artery for 2 weeks was completely covered with
      endothelial-like cells. On the other hand, the luminal surface of the iliac
      artery implanted with the CFC-sirolimus stent for 2 weeks only showed partial
      coverage with endothelial-like cells. While thrombosis was observed in two of the
      three CFC-sirolimus stents, it was observed in only one of the three AGC
      sirolimus stents. Taken together, these findings indicate that the designed
      nonuniform coating (AGC) is an appropriate approach to ensure a safer DES.
      However, the number of studies is limited and a larger study should be conducted
      to reach a statistically significant conclusion. 

PMID- 27051323
TI  - Investigating the health care delivery system in Japan and reviewing the local
      public hospital reform.
AB  - Japan's health care system is considered one of the best health care systems in
      the world. Hospitals are one of the most important health care resources in
      Japan. As such, we investigate Japanese hospitals from various viewpoints,
      including their roles, ownership, regional distribution, and characteristics with
      respect to the number of beds, staff, doctors, and financial performance.
      Applying a multivariate analysis and regression model techniques, we show the
      functional differences between urban populated prefectures and remote ones; the
      equality gap among all prefectures with respect to the distribution of the number
      of beds, staff, and doctors; and managerial differences between private and
      public hospitals. We also review and evaluate the local public hospital reform
      executed in 2007 from various financial aspects related to the expenditure and
      revenue structure by comparing public and private hospitals. We show that the
      2007 reform contributed to improving the financial situation of local public
      hospitals. Strategic differences between public and private hospitals with
      respect to their management and strategy to improve their financial situation are
      also quantitatively analyzed in detail. Finally, the remaining problems and the
      future strategy to further improve the Japanese health care system are described.

PMID- 27051324
TI  - The hypocretin/orexin system in sleep disorders: preclinical insights and
      clinical progress.
AB  - Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake
      regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin
      1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know,
      are intimately involved in the regulation wakefulness. The HCRT/OX system
      regulates sleep-wake control through complex interactions between
      monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic
      (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of
      sleep-wake control or stability with consequent unstable transitions between
      wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests
      clinically as abnormal daytime sleepiness with sleep attacks and cataplexy.
      Research on the development of HCRT/OX agonists and antagonists for the treatment
      of sleep disorders has dramatically increased with the US Food and Drug
      Administration approval of the first-in-class dual HCRT/OX receptor antagonist
      for the treatment of insomnia. This review focuses on the origin, mechanisms of
      HCRT/OX receptors, clinical progress, and applications for the treatment of sleep
      disorders. 

PMID- 27051325
TI  - Are we underestimating the lifelong benefits of therapy for obstructive sleep
      apnea?

PMID- 27051326
TI  - Study of knowledge and attitude among college-going students toward voluntary
      blood donation from north India.
AB  - INTRODUCTION: The study was conducted to assess the knowledge and attitude of
      college-going students toward voluntary blood donation and to bring out and
      compare the reasons for donating or not donating blood. MATERIALS AND METHODS:
      This cross-sectional study was conducted on 1,000 college-going students after
      taking their consent for participation using a prevalidated, self-administered,
      structured questionnaire after its content and construct validation. RESULTS: The
      difference in the means of the level of knowledge among the donor (mean: 14.71+/
      2.48) and nondonor students (mean: 11.55+/-2.82) was statistically significant.
      There was significant impact of previous blood donation on the level of knowledge
      in donor students. The attitude toward blood donation was more positive among
      blood donor as compared to nondonor students, and the difference in their means
      was statistically significant. About one in two (45.8%) college-going students
      fear that either they are not fit enough to donate blood (26.8%) or that they
      will become weak (19%) after blood donation. Almost one in four (27.4%) have fear
      of needle pain; therefore, they do not come forward for blood donation.
      INTERPRETATION AND CONCLUSION: The most significant reason hindering blood
      donation comes out to be related to health of the individual donor. The findings
      of this study conclude that the national targets of voluntary blood donation
      could be better met with specific blood donor information, education, motivation,
      and recruitment strategies focusing on the myths and misconceptions prevalent in
      the donor demographic area of that particular region, specifically targeting high
      school children in countries developing a volunteer donor base.

PMID- 27051327
TI  - Development and evaluation of a service-learning model for preclinical student
      education in cardiovascular disease prevention.
AB  - BACKGROUND: Cardiovascular diseases are the leading cause of preventable
      morbidity and mortality in the USA. Medical schools must prepare trainees to
      address prevention, including improving ability in counseling patients to modify
      lifestyle risk factors. Most medical students do not receive significant training
      or clinical experience in preventive medicine until the clinical years of medical
      school. To enhance student education in disease prevention and lifestyle
      counseling, and simultaneously target cardiovascular disease prevention in high
      risk Chicago neighborhoods, the Northwestern University Feinberg School of
      Medicine and Chicago Department of Public Health with support from the GE
      Foundation, developed the Keep Your Heart Healthy program. METHODS: Medical
      students participated in intensive faculty-led training. They subsequently
      screened local residents to identify and counsel for cardiovascular disease risk
      factors. Fifty-one predominantly preclinical medical students screened residents
      of the Humboldt Park and North Lawndale neighborhoods in Chicago, IL, at 31
      screening events from August to December 2013. Fifty students (98% response rate)
      completed a survey assessing the educational value of various program components
      following the pilot. RESULTS: Of all respondents, 92% of students reported
      improved knowledge of cardiovascular disease prevention and 94% reported improved
      knowledge of vulnerable populations and health equity. The majority (88%)
      reported that their participation supplemented material they learned in the
      classroom. Eighty-six percent of students reported that their encounters with
      community participants were of educational value. Integration of this program
      into the medical school curriculum was supported by 68% of students. CONCLUSION:
      Keep Your Heart Healthy educates primarily preclinical medical students in
      cardiovascular disease prevention and prepares them to apply this knowledge for
      patient counseling. Results from student surveys demonstrate that this service
      learning initiative enhances medical student knowledge in cardiovascular disease
      prevention, supplements classroom material, and provides students a valuable
      opportunity to apply interviewing and counseling skills in a real patient
      encounter.

PMID- 27051328
TI  - Improving the quality of psychiatry teaching within the UK undergraduate medical
      curriculum.

PMID- 27051329
TI  - Perspectives of interns and residents toward do-not-resuscitate policies in Saudi
      Arabia.
AB  - OBJECTIVE: Do-not-resuscitate (DNR) orders in Saudi Arabia were first regulated
      by a fatwa on a national level in 1988, one that excludes the patient and their
      families from decision making. Although the core of this policy is taken up by
      all hospitals in Saudi Arabia, there is no homogeneity in implementation. Here,
      we appraise what interns and residents know of these policies and their attitudes
      toward DNR. METHODS: Interns and residents in four major hospitals in Jeddah,
      King Abdulaziz University Hospital, National Guard Hospital, King Fahad General
      Hospital, and King Fahad Armed Forces Hospital, were given a questionnaire in
      English with four blocks of questions. RESULTS: A total of 140 questionnaires
      were included in our study. From these questionnaires, we conclude a lack of
      familiarity with DNR's policies and the fatwa and also a lack of understanding
      when it comes to treating DNR-labeled patients. The majority opinion was to
      include the patient in the decision-making process who is excluded according to
      the fatwa. Participants considered patients' dignity, religious concerns, and
      legal concerns to be important in considering resuscitation. CONCLUSION: We
      conclude a need to emphasize the issue of DNR and treatment of DNR patients in
      medical ethics classes in Saudi Arabia and put more effort to enact national DNR
      laws that include the patient in the decision-making process.

PMID- 27051330
TI  - Quality improvement teaching at medical school: a student perspective.
AB  - Guidelines in the UK require all doctors to actively take part in quality
      improvement. To ease future doctors into the process, formal quality improvement
      teaching can be delivered during medical school. 

PMID- 27051331
TI  - What basic clinical procedures should be mastered by junior clerkship students?
      Experience at a single medical school in Tanzania.
AB  - BACKGROUND: Clinical training in most medical schools, including the Catholic
      University of Health and Allied Sciences (CUHAS), is offered in the form of
      junior and senior rotations. During these clinical rotations, students are
      expected to acquire and master the basic procedural skills. However, students'
      learning process should be evaluated for quality improvement. OBJECTIVES: This
      study was conducted to identify the basic medical procedural skills that third
      year medical students should acquire and master and determine the level of
      students' exposure on these procedures at the end of junior rotation in internal
      medicine. Identification of the gap between clinicians' opinions, skills
      practiced by students, and third-year students' curriculum in the medical
      department at CUHAS was also done. METHODS: The descriptive cross-sectional study
      was used to collect data through a self-administered, structured questionnaire
      from clinicians in medicine. A review of logbooks was considered to determine
      level of students' exposure, and a document analysis was done using existing
      medical curriculum. RESULTS: The response of 71% (n=22) was obtained. Clinicians
      agreed on basic procedures that students should perform independently (ie, Foley
      catheter insertion, venipuncture, and intravenous drip insertion). Clinicians
      thought that lumbar punctures, abdominal paracentesis, and nasogastric tube
      insertion should be done under minimal supervision. A considerable number of
      students (25%, n=75) did not practice any procedure throughout their rotation.
      The majority of the students performed venipuncture independently (82.14%, n=56)
      and lumbar punctures (73.21%, n=56) under supervision. Less than 25% (n=56) of
      the students met the required number of exposures on the basic procedures. The
      procedures to be performed and the level of competency in the procedures are not
      specified in the current curriculum. CONCLUSION: The study identified the
      procedures that should be taught and practiced by students. It also highlighted
      the discrepancies in the existing curriculum and the need to monitor and
      supervise students' practice.

PMID- 27051332
TI  - Simulation experiences of paramedic students: a cross-cultural examination.
AB  - BACKGROUND: Simulation-based education is an important part of paramedic
      education and training. While accessing clinical placements that are adequate in
      quality and quantity continues to be challenging, simulation is being recognized
      by paramedic academics as a potential alternative. Examining students'
      satisfaction of simulation, particularly cross-culturally is therefore important
      in providing feedback to academic teaching staff and the international paramedic
      community. OBJECTIVE: This study aimed to compare simulation satisfaction among
      paramedic students from universities in Australia and Jordan. METHODS: A cross
      sectional study using a paper-based English version of the Satisfaction with
      Simulation Experience Scale was administered to paramedic students from all year
      levels. RESULTS: A total of 511 students participated in this study; 306 students
      (60%) from Australia (Monash University) and 205 students (40%) from Jordan
      (Jordan University of Science and Technology). There were statistically
      significant differences with large effect size noted in all three original
      factors between Australian and Jordanian students: debrief and feedback (mean
      =38.66 vs mean =34.15; P<0.001; d=0.86), clinical reasoning (mean =21.32 vs mean
      =18.28; P<0.001; d=0.90), and clinical learning (mean =17.59 vs mean =15.47;
      P<0.001; d=1.12). CONCLUSION: This study has demonstrated that simulation
      education is generally well received by students in Australia and Jordan although
      Australian students reported having higher satisfaction levels then their
      Jordanian counterparts. These results provide important data for paramedic
      educators involved in simulation-based education and training in Australia and
      Jordan and pave the way for other cross-cultural examinations to be explored.

PMID- 27051333
TI  - A review of gambling disorder and substance use disorders.
AB  - In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5), gambling disorder was recategorized from the "Impulse Control Disorder"
      section to the newly expanded "Substance-related and Addictive Disorders"
      section. With this move, gambling disorder has become the first recognized
      nonsubstance behavioral addiction, implying many shared features between gambling
      disorder and substance use disorders. This review examines these similarities, as
      well as differences, between gambling and substance-related disorders. Diagnostic
      criteria, comorbidity, genetic and physiological underpinnings, and treatment
      approaches are discussed. 

PMID- 27051334
TI  - Hepatitis E virus as an emerging zoonotic pathogen.
AB  - Hepatitis E outbreaks are a serious public health concern in developing
      countries. The disease causes acute infections, primarily in young adults. The
      mortality rate is approximately 2%; however, it can exceed 20% in pregnant women
      in some regions in India. The causative agent, hepatitis E virus (HEV), has been
      isolated from several animal species, including pigs. HEV genotypes 3 and 4 have
      been isolated from both humans and animals, and are recognized as zoonotic
      pathogens. Seroprevalence studies in animals and humans indirectly suggest that
      HEV infections occur worldwide. The virus is primarily transmitted to humans via
      undercooked animal meats in developed countries. Moreover, transfusion- and
      transplantation-mediated HEV infections have recently been reported. This review
      summarizes the general characteristics of hepatitis E, HEV infection status in
      animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine
      development status. 

PMID- 27051335
TI  - Reduction of adult hippocampal neurogenesis is amplified by aluminum exposure in
      a model of type 2 diabetes.
AB  - In this study, we investigated the effects of chronic aluminum (Al) exposure for
      10 weeks on cell proliferation and neuroblast differentiation in the hippocampus
      of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean
      control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups.
      Al was administered via drinking water for 10 weeks, after which the animals were
      sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed
      increases in body weight and blood glucose levels compared to ZLC rats. Al
      exposure did not significantly affect body weight, blood glucose levels or
      pancreatic beta-cells and morphology of the pancreas in either ZLC or ZDF rats.
      However, exposure to Al reduced cell proliferation and neuroblast differentiation
      in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the
      dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset
      and continuation of diabetes reduced cell proliferation and neuroblast
      differentiation, and Al exposure amplified reduction of these parameters. These
      results suggest that Al exposure via drinking water aggravates the impairment in
      hippocampal neurogenesis that is typically observed in type 2 diabetic animals. 

PMID- 27051336
TI  - Improved immunogenicity of Newcastle disease virus inactivated vaccine following
      DNA vaccination using Newcastle disease virus hemagglutinin-neuraminidase and
      fusion protein genes.
AB  - The present study describes the development of DNA vaccines using the
      hemagglutinin-neuraminidase (HN) and fusion (F) genes from AF2240 Newcastle
      disease virus strain, namely pIRES/HN, pIRES/F and pIRES-F/HN. Transient
      expression analysis of the constructs in Vero cells revealed the successful
      expression of gene inserts in vitro. Moreover, in vivo experiments showed that
      single vaccination with the constructed plasmid DNA (pDNA) followed by a boost
      with inactivated vaccine induced a significant difference in enzyme-linked
      immunosorbent assay antibody levels (p < 0.05) elicited by either pIRES/F,
      pIRES/F+ pIRES/HN or pIRES-F/HN at one week after the booster in specific
      pathogen free chickens when compared with the inactivated vaccine alone. Taken
      together, these results indicated that recombinant pDNA could be used to increase
      the efficacy of the inactivated vaccine immunization procedure. 

PMID- 27051337
TI  - Assessment of the safety and efficacy of low pathogenic avian influenza (H9N2)
      virus in inactivated oil emulsion vaccine in laying hens.
AB  - In Korea, several outbreaks of low pathogenic AI (H9N2) viral infections leading
      to decreased egg production and increased mortality have been reported on
      commercial farms since 1996, resulting in severe economic losses. To control the
      H9N2 LPAI endemic, the Korea Veterinary Authority has permitted the use of the
      inactivated H9N2 LPAI vaccine since 2007. In this study, we developed a killed
      vaccine using a low pathogenic H9N2 AI virus (A/chicken/Korea/ADL0401) and
      conducted safety and efficacy tests in commercial layer farms while focusing on
      analysis of factors that cause losses to farms, including egg production rate,
      egg abnormality, and feed efficiency. The egg production rate of the control
      group declined dramatically 5 days after the challenge. There were no changes in
      feed consumption of all three groups before the challenge, but rates of the
      control declined afterward. Clinical signs in the vaccinated groups were similar,
      and a slight decline in feed consumption was observed after challenge; however,
      this returned to normal more rapidly than the control group and commercial
      layers. Overall, the results of this study indicate that the safety and efficacy
      of the vaccine are adequate to provide protection against the AI field infection
      (H9N2) epidemic in Korea. 

PMID- 27051338
TI  - The association of Hsp90 expression induced by aspirin with anti-stress damage in
      chicken myocardial cells.
AB  - The protective effect of aspirin during exposure to heat stress in broiler
      chickens was investigated. We assayed pathological damage, expression and
      distribution of Hsp90 protein and hsp90 mRNA expression in chicken heart tissues
      after oral administration of aspirin following exposure to high temperature for
      varying times. Heat stress induced increases in plasma aspartate
      aminotransferase, creatine kinase and lactate dehydrogenase activities while
      causing severe heart damage, which was characterized by granular and vacuolar
      degeneration, nuclear shrinkage and even myocardium fragmentation in cardiac
      muscle fibers. After aspirin administration, myocardial cells showed fewer
      pathological lesions than broilers treated with heat alone. A high positive Hsp90
      signal was always detected in the nuclei of myocardial cells from broilers
      treated with aspirin, while in myocardial cells treated with heat alone, Hsp90 in
      the nuclei decreased, as did that in the cytoplasm. Aspirin induced rapid and
      significant synthesis of Hsp90 before and at the initial phase of heat stress,
      and significant expression of hsp90 mRNA was stimulated throughout the experiment
      when compared with cells exposed to heat stress alone. Thus, specific pre
      induction of Hsp90 in cardiovascular tissue was useful for resisting heat stress
      damage because it produced stable damage-related enzymes and fewer pathologic
      changes. 

PMID- 27051339
TI  - Time-course changes in the expression levels of miR-122, -155, and -21 as markers
      of liver cell damage, inflammation, and regeneration in acetaminophen-induced
      liver injury in rats.
AB  - Drug-induced liver injury (DILI) is a significant threat to patient health and a
      major concern during drug development. Recently, multiple circulating microRNAs
      (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and
      validate miRNAs for clinical use, we investigated the time-course changes in miR
      122 expression levels in an acetaminophen-induced liver injury model in rats. In
      addition, miR-155 and miR-21 were evaluated as makers of inflammation and
      regeneration, respectively, to characterize liver status. Our results revealed
      that miR-122 is an early and sensitive biomarker of hepatocellular injury at a
      stage when alanine transaminase, aspartate transaminase, and total bilirubin were
      not detectable. However, no significant differences in the expression levels of
      other miRNAs (miR-155 and -21) were observed between treatment and vehicle
      groups. Collectively, these time-course changes in the expression levels of
      miRNAs may be useful as markers for clinical decision-making, in the diagnosis
      and treatment of DILI. 

PMID- 27051340
TI  - Agmatine protection against chlorpromazine-induced forebrain cortex injury in
      rats.
AB  - This study was conducted to investigate whether agmatine (AGM) provides
      protection against oxidative stress induced by treatment with chlorpromazine
      (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and
      efficiency of antioxidant protection in the brain homogenates of forebrain
      cortexes prepared 48 h after treatment were investigated. Chlorpromazine was
      applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW)
      The second group was treated with both CPZ and AGM (75 mg/kg BW). The control
      group was treated with 0.9% saline solution in the same manner. All tested
      compounds were administered i.p. in a single dose. Rats were sacrificed by
      decapitation 48 h after treatment Treatment with AGM significantly attenuated the
      oxidative stress parameters and restored antioxidant capacity in the forebrain
      cortex. The data indicated that i.p. administered AGM exerted antioxidant action
      in CPZ-treated animals. Moreover, reactive astrocytes and microglia may
      contribute to secondary nerve-cell damage and participate in the balance of
      destructive vs. protective actions involved in the pathogenesis after poisoning. 

PMID- 27051341
TI  - Gap junction blockage promotes cadmium-induced apoptosis in BRL 3A derived from
      Buffalo rat liver cells.
AB  - Gap junctions mediate direct communication between cells; however, toxicological
      cascade triggered by nonessential metals can abrogate cellular signaling mediated
      by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs
      and tissues, the mechanisms that underlie gap junction activity in Cd-induced
      apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we
      showed that Cd treatment decreased the cell index (a measure of cellular
      electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure
      decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and
      elevated intracellular free Ca(2+) concentration, corresponding to a decrease in
      gap junctional intercellular communication. Gap junction blockage pretreatment
      with 18beta-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving
      changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial
      transmembrane electrical potential (Deltapsim). Additionally, GA was found to
      enhance ERK and p38 activation during Cd-induced activation of mitogen-activated
      protein kinases, but had no significant effect on JNK activation. Our results
      indicated the apoptosis-related proteins and the ERK and p38 signaling pathways
      may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A
      cells. 

PMID- 27051342
TI  - A novel M2e-multiple antigenic peptide providing heterologous protection in mice.
AB  - Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in
      domestic pigs, resulting in a significant economic burden. Moreover, pigs have
      been considered to be a possible mixing vessel in which novel strains loom. Here,
      we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a
      supplemental antigen for inactivated H3N2 vaccine to provide cross-protection
      against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP
      was constructed by fusing four copies of M2e to one copy of foreign T helper cell
      epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based
      reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or
      without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP
      conjugated vaccine induced strong antibody responses in mice. Complete protection
      against the heterologous swine H1N1 virus was observed in mice vaccinated with
      M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against
      lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results
      suggest the combined immunization of reassortant inactivated H3N2 vaccine and the
      novel M2e-MAP provided cross-protection against swine and human viruses and may
      serve as a promising approach for influenza vaccine development. 

PMID- 27051343
TI  - Effect of autologous platelet-rich plasma application on cutaneous wound healing
      in dogs.
AB  - This study was conducted to identify the effectiveness of platelet-rich plasma
      (PRP) and efficacy of intralesional injection as a method of application to acute
      cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study.
      Autologous PRP was separated from anticoagulant treated whole blood in three
      dogs. Cutaneous wounds were created and then treated by intralesional injection
      of PRP in the experimental group, while they were treated with saline in the
      control group on days 0, 2 and 4. The healing process was evaluated by gross
      examination throughout the experimental period and histologic examination on day
      7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound
      closure rate was higher than in the control. Histological study revealed that PRP
      treated wounds showed more granulation formation and angiogenesis on day 7, and
      faster epithelialization, more granulation formation and collagen deposition were
      observed on day 14 than in control wounds. On day 21, collagen deposition and
      epithelialization were enhanced in PRP treated groups. Overall, PRP application
      showed beneficial effects in wound healing, and intralesional injection was
      useful for application of PRP and could be a good therapeutic option for wound
      management in dogs. 

PMID- 27051344
TI  - Production of alpha1,3-galactosyltransferase targeted pigs using transcription
      activator-like effector nuclease-mediated genome editing technology.
AB  - Recent developments in genome editing technology using meganucleases demonstrate
      an efficient method of producing gene edited pigs. In this study, we examined the
      effectiveness of the transcription activator-like effector nuclease (TALEN)
      system in generating specific mutations on the pig genome. Specific TALEN was
      designed to induce a double-strand break on exon 9 of the porcine alpha1,3
      galactosyltransferase (GGTA1) gene as it is the main cause of hyperacute
      rejection after xenotransplantation. Human decay-accelerating factor (hDAF) gene,
      which can produce a complement inhibitor to protect cells from complement attack
      after xenotransplantation, was also integrated into the genome simultaneously.
      Plasmids coding for the TALEN pair and hDAF gene were transfected into porcine
      cells by electroporation to disrupt the porcine GGTA1 gene and express hDAF. The
      transfected cells were then sorted using a biotin-labeled IB4 lectin attached to
      magnetic beads to obtain GGTA1 deficient cells. As a result, we established GGTA1
      knockout (KO) cell lines with biallelic modification (35.0%) and GGTA1 KO cell
      lines expressing hDAF (13.0%). When these cells were used for somatic cell
      nuclear transfer, we successfully obtained live GGTA1 KO pigs expressing hDAF.
      Our results demonstrate that TALEN-mediated genome editing is efficient and can
      be successfully used to generate gene edited pigs. 

PMID- 27051345
TI  - Expression of neurotrophic factors in injured spinal cord after transplantation
      of human-umbilical cord blood stem cells in rats.
AB  - We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45
      rats and transplanted human umbilical cord blood derived mesenchymal stem cells
      (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in
      hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured
      spinal cord showed increased expression of brain-derived neurotrophic factor
      (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show
      that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest
      that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the
      main therapeutic effect. 

PMID- 27051346
TI  - Time-dependent low-field MRI characteristics of canine blood: an in vitro study.
AB  - This study was conducted to assess time-sensitive magnetic resonance (MR) changes
      in canine blood using low-field MR. Arterial and venous blood samples were
      collected from eight healthy beagle dogs. Samples were placed in 5-mL tubes and
      imaged within 3 hours of collection at 1 day intervals from day 1 to day 30. The
      following sequences were used: T1-weighted (T1W), T2-weighted (T2W), fluid
      attenuated inversion recovery (FLAIR), short tau inversion recovery (STIR), and
      T2-star gradient-echo (T2(*)-GRE). Visual comparison of the images revealed that
      four relatively homogenous blood clots and twelve heterogeneous blood clots
      developed. The margination of the clot and plasma changed significantly on day 2
      and day 13. On day 2, heterogeneous blood clots were differentiated into 2 to 3
      signal layers in the T2W, T1W, and especially the STIR images. Hypointense signal
      layers were also detected in the blood clots in STIR images, which have T2 hypo,
      FLAIR hypo, and T1 hyper intense signals. In all images, these signal layers
      remained relatively unchanged until day 13. Overall, the results suggest that
      hematomas are complex on low-field MRI. Accordingly, it may not be feasible to
      accurately characterize hemorrhages and predict clot age based on low-field MRI. 

PMID- 27051347
TI  - Postnatal exposure to a progestin does not prevent uterine adenogenesis in
      domestic dogs.
AB  - To assess the effects of a single supraphysiological postnatal administration of
      a progestogen on uterine glands in dogs, 10 females were randomly assigned to a
      medroxyprogesterone acetate 35 mg (MPA; n = 6) or placebo (n = 4) group within
      the first 24 h of birth. The safety of the treatment was also evaluated. A
      transient mild clitoris enlargement appeared in MPA-treated females. Microscopic
      postpubertal uterine assessment revealed the presence of uterine glands in all
      cases without significant differences in the area occupied by the glands per
      um(2) of endometrium nor in the height of the uterine epithelium. 

PMID- 27051349
TI  - Molecular cloning, purification and immunogenicity of recombinant Brucella
      abortus 544 malate dehydrogenase protein.
AB  - The Brucella mdh gene was successfully cloned and expressed in E. coli. The
      purified recombinant malate dehydrogenase protein (rMDH) was reactive to Brucella
      positive bovine serum in the early stage, but not reactive in the middle or late
      stage, and was reactive to Brucella-positive mouse serum in the late stage, but
      not in the early or middle stage of infection. In addition, rMDH did not react
      with Brucella-negative bovine or mouse sera. These results suggest that rMDH has
      the potential for use as a specific antigen in serological diagnosis for early
      detection of bovine brucellosis. 

PMID- 27051348
TI  - Viscerotropic velogenic Newcastle disease virus replication in feathers of
      infected chickens.
AB  - Newcastle disease viruses (NDVs) cause systemic diseases in chickens with high
      mortality. However, little is known about persistence of NDVs in contaminated
      tissues from infected birds. In this study, we examined viral replication in the
      feather pulp of chickens inoculated with viscerotropic velogenic NDV (vvNDV)
      genotype VII. Reverse transcription real-time PCR and immunohistochemistry were
      used to investigate viral persistence in the samples. vvNDV was detected in the
      oropharynx and cloaca and viral antigens were detected in the feathers,
      suggesting that feathers act as sources of viral transmission. 

PMID- 27051350
TI  - Transplantation of adipose derived mesenchymal stem cells for acute thoracolumbar
      disc disease with no deep pain perception in dogs.
AB  - Thirty-four dogs with no deep pain perception due to acute thoracolumbar
      intervertebral disc disease underwent decompression surgery within 1 week of
      diagnosis. All dogs underwent hemilaminectomy. Adipose derived mesenchymal stem
      cells (AD-MSCs) were transplanted into the injured spinal cord parenchyma for the
      AD-MSCs transplant dogs. Long-term outcome was evaluated at the end of the follow
      up period (> 6 months). AD-MSCs combination treatment showed better recovery
      outcomes compared to decompression surgery alone. These results indicate that
      this stem cell therapy is a potential therapeutic strategy to overcome the
      limitations of treatment for spinal cord injury in clinical medicine. 

PMID- 27051351
TI  - What are the 'necessary' skills for a newly graduating RN? Results of an
      Australian survey.
AB  - BACKGROUND: There appears to be a sense of disappointment with the product of
      contemporary nursing programs in Australia in that new graduate RNs are often
      referred to as not possessing appropriate skills by clinical colleagues. This
      work identifies the skills that the profession believes that newly graduating
      RN's should possess at the point of registration. METHODS: A qualitative
      consensus methodology was used in the form of a modified Delphi survey. Expert
      panels were used to review and validate data. RESULTS: Consensus was reached on
      the top 25 skills areas that can be reasonably expected of a new graduate
      Registered Nurse in Australia. The top ranked skills areas included efficient and
      effective communication, professional nursing behaviours, privacy and dignity and
      managing medication administration. CONCLUSIONS: The consensus methodologies used
      to develop the skills areas indicated broad agreement across the profession in
      Australia. The complexity and context of practice was highlighted in the comments
      within the Delphi rounds. Interestingly no new skills were added and none removed
      from the initial list - some were prioritised over others but the majority agreed
      that all the skills areas were important for a newly graduating nurse.

PMID- 27051352
TI  - Erratum to: Estimation of country-specific and global prevalence of male
      circumcision.
AB  - [This corrects the article DOI: 10.1186/s12963-016-0073-5.]. 

PMID- 27051353
TI  - Measuring and tracking obesity inequality in the United States: evidence from
      NHANES, 1971-2014.
AB  - BACKGROUND: Because people care about their weight relative to peers and society,
      obesity inequality plays a role in explaining obesity incidence and the impacts
      of being obese on subjective well-being. While the increase in obesity prevalence
      and mean body mass index (BMI) is well documented, the measurement of
      distributional changes and corresponding obesity inequality is yet to be fully
      explored. METHODS: The present study analyzed BMI data for adults aged 20 to 74
      from the National Health and Nutritional Examination Survey (NHANES) I (1971
      1974), II (1976-1980), III (1988-1994), and continuous NHANES (1999-2014). We
      applied tools developed to measure income inequality to analyze the inter
      temporal variation in the BMI distribution among US adults. Using stochastic
      dominance tests, we construct partial orderings on cumulative BMI distributions
      during the study period. Shapley decompositions and inequality indices are
      employed to quantify the source and extent of temporal variation and decompose
      the inequality into within and between-group components considering age, gender,
      and race. RESULTS: The BMI distribution of each NHANES study first-order
      stochastically dominated the BMI distribution of the previous wave from 1971-1974
      to 2003-2006, whereas more recent comparisons failed to reject the null
      hypothesis of non-dominance. The Shapley decomposition analysis revealed that
      horizontal shifts of BMI distributions accounted for a majority of the increase
      in obesity prevalence since 1988-1991. Especially in recent years when the rate
      of obesity growth has slowed down, the contribution of the redistribution
      component dropped significantly and even became negative between 2007-2010 and
      2011-2014. The inequality indexes consistently show a worsening of obesity
      inequality from the mid-1970s to the mid-2000s regardless of population
      subgroups, and this disproportionate shift of the BMI distribution is unlikely to
      be a result of a changing ethnic composition of the US population. CONCLUSION:
      Our findings demonstrate that seemingly similar increases in obesity prevalence
      can be accompanied by very different patterns of distribution change. We find
      that the early phase of the obesity epidemic in the US was largely driven by
      increasing skewness, whereas more recent growth is a population-wide experience,
      regardless of demographic characteristics. Increasing morbid obesity certainly
      played an important role in the initial phase of the epidemic, but more recently
      the BMI distribution has largely horizontally shifted to the right.

PMID- 27051354
TI  - Effects of dietary Docosahexaenoic, training and acute exercise on lipid
      mediators.
AB  - BACKGROUND: Eicosanoids mediate initiation and resolution of inflammation. Our
      aim was evaluating the effects of training, exercise and docosahexaenoic (DHA)
      supplementation on plasma eicosanoids levels and peripheral blood mononuclear
      cells (PBMCs) eicosanoids production. METHODS: Fifteen male footballers were
      distributed to placebo and experimental groups. Experimental group consumed DHA
      enriched beverage (1.16 g DHA/day) for 8 weeks, placebo group consumed a placebo
      beverage. Blood samples were taken before and after the nutritional intervention
      in basal conditions and 2 h after acute exercise. RESULTS: Training increased
      basal Prostaglandin E1 (PGE1) plasma levels and PBMCs cyclooxygenase 2 (COX-2)
      protein levels in both groups, but COX-1 protein levels only in the experimental
      group. Acute exercise increased plasma PGE2 and PBMCs active NFkappabeta levels.
      Lipopolysaccharide (LPS)-stimulated PBMCs increases eicosanoids production (PGE1,
      PGE2, RvD1) in both groups and increased LPS-stimulated PBMCs active NFkappabeta.
      DHA supplementation increased COX-2 levels but decreased LPS-stimulated PBMCs
      PGE1 and PGE2 production. Neither DHA supplementation nor acute exercise altered
      the expression of NFkappabeta, COX-2, 15-LOX2, 5-LOX, or IL-1beta genes in PBMCs.
      CONCLUSIONS: The increase of PGE1 plasma levels after training promoted systemic
      anti-inflammatory and vasodilator environment. Exercise and DHA supplementation
      acted synergistically by increasing plasma PGE2 with anti-inflammatory effects.
      Exercise primed PBMCs to enhance PGE1, PGE2 and RvD1 production in response to
      LPS. TRIAL REGISTRATION: The project was registered at ClinicalTrial.gov
      (NCT02177383).

PMID- 27051355
TI  - Clinical utility of serum biomarkers in Duchenne muscular dystrophy.
AB  - Assessments of disease progression and response to therapies in Duchenne muscular
      dystrophy (DMD) patients remain challenging. Current DMD patient assessments
      include complex physical tests and invasive procedures such as muscle biopsies,
      which are not suitable for young children. Defining alternative, less invasive
      and objective outcome measures to assess disease progression and response to
      therapy will aid drug development and clinical trials in DMD. In this review we
      highlight advances in development of non-invasive blood circulating biomarkers as
      a means to assess disease progression and response to therapies in DMD. 

PMID- 27051356
TI  - Exposure to active and passive smoking among Greek pregnant women.
AB  - BACKGROUND: Active smoking and exposure to passive smoke are responsible for
      numerous adverse pregnancy outcomes for women and their infants. The aim of this
      study was to explore the perceptions, attitudes, patterns of personal tobacco use
      and exposure to environmental smoke among a sample of pregnant women in Greece.
      METHOD: A cross sectional survey was undertaken of 300 women identified from the
      perinatal care records of the Maternity Departments of two hospitals in Athens
      between February 2013 and May 2013. Data on active and passive maternal smoking
      status in the first, second, and third trimesters of pregnancy, fetal and
      neonatal tobacco related complications, exposure to environmental tobacco smoke
      during pregnancy, quit attempts, behaviors towards avoiding passive smoking and
      beliefs towards smoking cessation during pregnancy were collected using self
      administered questionnaires on the 3rd postnatal day. Women also completed the
      Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Of 300 women recruited to
      the study 48 % reported tobacco use during the first trimester of pregnancy.
      Amongst participants who were tobacco users, 83.3 % reported making an attempt to
      quit but less than half (45.1 %) were successful. Among women who continued to
      smoke during pregnancy the majority (55.8 %) reported that they felt unable to
      quit, and 9.3 % reported that they considered smoking cessation was not an
      important health issue for them. Participants who continued to smoke during
      pregnancy were more likely to report fetal (chi2 = 11.41; df = 5; p < 0.05) and
      newborn complications (chi2 = 6.41; df = 2; p < 0.05), including preterm birth
      and low birth weight. Participants who reported that their partners were smokers
      were more likely to smoke throughout their pregnancy (chi2 = 14.62; df = 1; p <
      0.001). High rates of second-hand smoke exposure were reported among both smoking
      and non-smoking women. Pregnant smokers had significantly higher levels of
      postnatal depressive and anxiety symptomatology, as measured using the EPDS, than
      non-smokers. CONCLUSION: Our data supports the importance of ensuring that
      pregnant women, their partners and close relatives are educated on the health
      risks of active and passive smoking and how these could have an adverse effect to
      their fetus and infants, as well as the pregnant women themselves.

PMID- 27051357
TI  - Chinese smokers' behavioral response toward cigarette price: individual and
      regional correlates.
AB  - BACKGROUND: Many studies have explored smokers' behavioral response to cigarette
      prices at the individual level, but none have factored in regional variation and
      determinants. This study addresses these research gaps in the Chinese context.
      METHODS: A cross-sectional multistage sampling process was used to recruit
      participants in 21 cities in China. Individual-level information was collected
      using standardized questionnaires. City-level variables were retrieved from a
      nationall database. Multilevel logistic regression analysis was used to assess
      price sensitivity variation at both individual and city levels. RESULTS: Among
      5660 current smokers, 5.9 % used non-self-paying cigarettes, 32.8 % purchased
      cigarettes in cartons, and 5.2 % decreased their smoking expenditure due to
      price. Multilevel analysis showed that individual demographic and smoking
      expenditure characteristics and regional smoking restrictions in work places,
      cigarette production, and media news coverage are associated with price
      sensitivity. CONCLUSIONS: This study adds substantially to the understanding of
      Chinese smokers' behavioral responses to cigarette prices. Increasing smoker
      sensitivity to cigarette prices will require stronger tobacco control and public
      education campaigns.

PMID- 27051358
TI  - Is enhanced recovery after anesthesia a synonym to enhanced recovery after
      surgery?

PMID- 27051359
TI  - A comparison between intrathecal clonidine and neostigmine as an adjuvant to
      bupivacaine in the subarachnoid block for elective abdominal hysterectomy
      operations: A prospective, double-blind and randomized controlled study.
AB  - BACKGROUND AND AIMS: Adjuvant to the local anesthetic agent has proven benefits
      when used intrathecally. With regards to intrathecal bupivacaine as control, we
      have compared in this study the effects of clonidine and neostigmine when co
      administered intrathecally with hyperbaric (0.5%) bupivacaine for abdominal
      hysterectomy. MATERIALS AND METHODS: This prospective, randomized, double-blind
      study was conducted from May 2009 to June 2011. A total of 150 patients of
      American Society of Anaesthesiology grades I and II scheduled for abdominal
      hysterectomy under spinal anesthesia were randomly allocated into three groups. A
      volume of 3 ml of 0.5% hyperbaric bupivacaine was respectively added 1 ml
      solution containing 5% dextrose and 75 mcg of neostigmine in Group N, 1 ml
      containing 5% dextrose and 30 mcg of clonidine in Group C and 1 ml of 5% dextrose
      in Group D (control). We compared the sensory and motor block, the surgical
      condition, the duration of spinal analgesia and the side-effect profile. RESULTS
      AND OBSERVATIONS: Sensory and motor blocks and duration of spinal analgesia were
      significantly increased in both Group C and Group N compared to Group D. More
      incidences of Nausea and vomiting were observed in Group N compared to other
      groups. The surgical condition was poorer in Group N compared to Group C.
      CONCLUSION: Both intrathecal clonidine and neostigmine increase the bupivacaine
      induced spinal block. However, clonidine provides better surgical condition and
      fewer incidences of nausea and vomiting.

PMID- 27051360
TI  - Effect of introduction of a new electronic anesthesia record (Epic) system on the
      safety and efficiency of patient care in a gastrointestinal endoscopy suite
      comparison with historical cohort.
AB  - BACKGROUND: Use of electronic medical record systems has increased in the recent
      years. Epic is one such system gaining popularity in the USA. Epic is a private
      company, which invented the electronic documentation system adopted in our
      hospital. In spite of many presumed advantages, its use is not critically
      analyzed. Some of the perceived advantages are increased efficiency and
      protection against litigation as a result of accurate documentation. MATERIALS
      AND METHODS: In this study, retrospective data of 305 patients who underwent
      endoscopic retrograde cholangiopancreatography (wherein electronic charting was
      used - "Epic group") were compared with 288 patients who underwent the same
      procedure with documentation saved on a paper chart ("paper group"). Time of
      various events involved in the procedure such as anesthesia start, endoscope
      insertion, endoscope removal, and transfer to the postanesthesia care unit were
      routinely documented. From this data, the various time durations were calculated.
      RESULTS: Both "anesthesia start to scope insertion" times and "scope removal to
      transfer" times were significantly less in the Epic group compared to the paper
      group. Use of Epic system led to a saving of 4 min of procedure time per patient.
      However, the mean oxygen saturation was significantly less in the Epic group.
      CONCLUSION: In spite of perceived advantages of Epic documentation system,
      significant hurdles remain with its use. Although the system allows seamless flow
      of patients, failure to remove all artifacts can lead to errors and become a
      source of potential litigation hazard.

PMID- 27051361
TI  - Effect of intraoperative magnesium intravenous infusion on the hemodynamic
      changes associated with right lobe living donor hepatotomy under transesophageal
      Doppler monitoring-randomized controlled trial.
AB  - BACKGROUND: Liver donors are subjected to specific postresection hemodynamic
      changes. The aim was to monitor these changes and to evaluate the effect of
      magnesium sulfate infusion (MgSO4) on these changes together with total
      anesthetic agents consumption. PATIENTS AND METHODS: A total of 50 donors
      scheduled for right hepatotomy were divided into two equal groups. Controls (C)
      received saline and magnesium group (Mg) received MgSO4 10% (30 mg/kg over 20
      min) administered immediately after induction of anesthesia, followed by infusion
      (10 mg/kg/h) till the end of surgery. Hemodynamics, transesophageal Doppler (TED)
      data and anesthetic depth guided by Entropy were recorded. RESULTS: Postresection
      both groups demonstrated an increase in heart rate (HR) and cardiac output (COP)
      in association with lowering of systemic vascular resistance (SVR). The increase
      in HR with Mg was lower when compared with C, P = 0.00. Increase in COP was lower
      with Mg compared to (C) (6.1 +/- 1.3 vs. 7.5 +/- 1.6 L/min, P = 0.00) and with
      less reduction in SVR compared to C (1145 +/- 251 vs. 849.2 +/- 215
      dynes.s/cm(5), P < 0.01), respectively. Sevoflurane consumption was lower with Mg
      compared to C (157.1 +/- 35.1 vs. 187.6 +/- 25.6 ml, respectively, P = 0.001).
      Reduced fentanyl and rocuronium consumption in Mg group are compared to C (P =
      0.00). Extubation time, postoperative patient-controlled fentanyl were lower in
      Mg than C (P = 0.001). CONCLUSION: TED was able to detect significant hemodynamic
      changes associated with major hepatotomy. Prophylactic magnesium helped to reduce
      these changes with lower anesthetic and analgesics consumption and an improvement
      in postoperative pain relief.

PMID- 27051362
TI  - Efficacy of two doses of tramadol versus bupivacaine in perioperative caudal
      analgesia in adult hemorrhoidectomy.
AB  - BACKGROUND: The study was conducted to evaluate the perioperative analgesic
      efficacy of the two doses of caudally administered tramadol versus bupivacaine in
      adult hemorrhoidectomy. PATIENTS AND METHODS: A total of 90 patients, aged 20-50
      years, undergoing hemorrhoidectomy were randomly scheduled to receive bupivacaine
      0.25% in 20 ml (Group B; n = 30), tramadol 1 mg/kg in 20 ml (Group T1; n = 30),
      tramadol 2 mg/kg in 20 ml (Group T2; n = 30) through caudal route after induction
      of general anesthesia. Postoperative pain was assessed every hour until the
      visual analog scale was 6, which is 1(st) time for rescue analgesia.
      Postoperative sedation, hemodynamic changes, serum cortisol, and epinephrine
      levels and incidence of side effects were also evaluated. RESULTS: Duration of
      analgesia was longer in Group T2 (20 [1.14] h] compared with the Group B (7 [1.2]
      h) or Group T1 (12 [0.75] h); all P < 0.001. There were no significant
      hemodynamic changes. There were not incidences of side effects. CONCLUSION:
      Caudal tramadol 2 mg/kg provided a longer duration of postoperative analgesia
      with rapid onset and no incidence of complications or adverse effects in adult
      hemorrhoidectomy.

PMID- 27051363
TI  - Supraclavicular ultrasound-guided catheterization of the brachiocephalic vein in
      infants and children: A retrospective analysis.
AB  - OBJECTIVE/BACKGROUND: Ultrasound (US) facilitates central venous catheter (CVC)
      placement in children. A new supraclavicular approach using the brachiocephalic
      vein (BCV) for US-guided CVC placement in very small children has been recently
      described. In 2012, we changed our departmental standard and used the left BCV as
      preferred puncture site during CVC placement. In our retrospective analysis, we
      compared US-guided cannulation of the BCV with other puncture sites (control).
      DESIGN/MATERIALS AND METHODS: We performed a retrospective analysis of all CVC
      cannulations from October 2012 to October 2013 in our department. For cannulation
      of the BCV, the in-plane technique was used to guide the needle into the target
      vein. RESULTS: We performed CVC cannulations in 106 children (age 1-day to 18
      years). In 29 patients, the weight was <4.5 kg. CVC placement was successful in
      all patients. The left BCV could be used in 81.1% of all cases. In a Poisson
      regression model of punctures regressed by age, weight or group (left BCV vs.
      control), age, weight or the cannulation site did not influence the number of
      punctures. In a logistic regression model of complications (yes vs. no) regressed
      by the group (left brachiocephalic vs. control) an odds ratio of 0.15 was
      observed (95% confidence interval 0.03-0.72, P likelihood ratio test = 0.007).
      CONCLUSION: US-guided puncture of the left BCV is a safe method of CVC placement
      in children. The use of the left BCV was associated with a high success rate in
      our retrospective analysis.

PMID- 27051364
TI  - Incidence of lower limb motor weakness in patients receiving postoperative
      epidural analgesia and factors associated with it: An observational study.
AB  - INTRODUCTION AND AIM: Epidural analgesia is an effective technique for
      postoperative pain relief following thoracoabdominal surgeries. Lower limb motor
      weakness is a well-known complication of epidural analgesia with local
      anesthetics and delays postoperative rehabilitation. Our aim in conducting this
      observational study was to assess the frequency of lower limb motor weakness in
      patients receiving epidural analgesia following upper abdominal surgery and the
      factors associated with it. MATERIALS AND METHODS: All adult patients, aged 20-70
      years, who underwent upper abdominal surgery and received postoperative analgesia
      with an epidural infusion of bupivacaine with fentanyl, were included. Data were
      collected over 4 months from notes entered by acute pain service after each
      round. Data collected included level of epidural placement, drug solution and
      volume, degree of lower limb motor weakness and measures taken to relieve it.
      Bromage scale was used to assess motor weakness. RESULTS: Data were collected on
      123 patients. Bupivacaine 0.1% with fentanyl 2 MUg/mL was used in 113 (92%)
      patients. Lower limb motor weakness developed in 45 patients (36.5%). The highest
      frequency was seen in patients with epidural at L2-L3 level. The common
      management steps were a change of patient's position or decrease in concentration
      of local anesthetic. These measures produced improvement in 39 (87%) patients
      whereas the local anesthetic was stopped temporarily in the remaining six
      patients. CONCLUSION: Lower limb motor weakness occurred in 36.5% patients. It
      was more common with a lumbar epidural. It was successfully managed in all
      patients. Lower thoracic epidurals are recommended for abdominal surgeries.

PMID- 27051365
TI  - Comparison of caudal tramadol versus caudal fentanyl with bupivacaine for
      prolongation of postoperative analgesia in pediatric patients.
AB  - BACKGROUND AND AIMS: Caudal block is a common technique for pediatric analgesia
      for infraumblical surgeries. Because of the short duration of analgesia with
      bupivacaine alone various additive have been used to prolong the action of
      bupivacaine. The present study was aimed to evaluate the analgesic effect of
      tramadol or fentanyl added to bupivacaine for infraumblical surgeries in
      pediatric patients. MATERIALS AND METHODS: We conducted a prospective,
      randomized, single-blind controlled trial. After written informed consent from
      parents, 100 patients belonging to American Society of Anesthesiologist physical
      status I-II, in the age group of 1-12 years, of either sex undergoing
      infraumblical surgery under general anesthesia were divided into two groups.
      Group BT received 1 ml/kg of 0.25% bupivacaine with tramadol 2 mg/kg in normal
      saline and Group BF received 1 ml/kg of 0.25% bupivacaine with fentanyl 2 MUg/kg
      in normal saline with maximum volume of 12 ml in both groups. All patients were
      assessed intraoperatively for hemodynamic changes, the requirement of sevoflurane
      concentration, as well as postoperatively for pain by using FLACC (F = Face, L =
      Leg, A = Activity, C = Cry, C = Consolability), pain score and for sedation by
      using four point sedation score. RESULTS: The mean duration of analgesia was 10
      18 h in Group BT while in Group BF it was 7-11 h. The postoperatively period up
      to 11/2 h, Group BF had higher sedation score up to two as compared to that below
      one on Group BT. CONCLUSION: Caudal tramadol significantly prolongs the duration
      of analgesia as compared to caudal fentanyl without any side effects.

PMID- 27051366
TI  - Evaluation of new approach to ultrasound guided stellate ganglion block.
AB  - BACKGROUND: Ultrasound imaging is an ideal tool for stellate ganglion block (SGB)
      due to clarity, portability, lack of radiation, and low cost. Ultrasound guided
      anterior approach requires the application of pressure to the anterior neck and
      is associated with more risk of injury to inferior thyroid artery, vertebral
      artery, and esophagus. The lateral approach does not interfere with nerve or
      vascular structures. Blockade at the C6 vertebral level results in more
      successful sympathetic blockade of the head and neck with less sympathetic
      blockade of the upper extremity compared to sympathetic blockade at C7 vertebral
      level, which produces successful sympathetic blockade of upper extremity. This is
      helpful in patients of complex regional pain syndrome of the upper limb. Hence,
      we conducted a study using the lateral approach at C7 level. MATERIALS AND
      METHODS: Ultrasound guided SGBs using lateral in-plane technique at C7 level were
      given in 20 patients suffering from chronic pain patients of upper extremity,
      head, and neck using 4 ml of 0.25% bupivacaine and 1 ml of 40 mg triamcinolone.
      The patients were assessed for a numeric pain intensity score (NPIS), the rise in
      axillary temperature, the range of motion of joints of upper extremity, and
      resolution of edema at various time intervals up to 3 months. RESULTS: NPIS
      showed a statistically significant decrease from baseline at 30 min, which was
      sustained till 3(rd) month. The rise in axillary temperature after the block was
      statistically significant, which was sustained till 2(nd) week. The edema score
      decreased significantly at all-time intervals (P <= 0.001). The restriction of
      motion in all joints of upper limb decreased from 13 to 3 patients. CONCLUSION:
      There is a significant variation in the anatomy of stellate ganglion at the level
      of C6 and C7. Ultrasound guided lateral approach increases the efficacy of SGB by
      deposition of drug subfascially with real-time imaging.

PMID- 27051368
TI  - Does caval aorta index correlate with central venous pressure in intravascular
      volume assessment in patients undergoing endoscopic transuretheral resection of
      prostate?
AB  - BACKGROUND AND OBJECTIVE: Ultrasonography has been suggested as a useful
      noninvasive tool for intravascular volume assessment in critically ill-patients.
      Fluid absorption is an inevitable complication of transurethral resection of the
      prostate (TURP). However, there are few data comparing the caval aortic index
      with central venous pressure (CVP) measurement for intravascular volume
      assessment in patients undergoing TURP. MATERIALS AND METHODS: This is a
      prospective observer blinded study carried out on 50 patients who underwent
      elective TURP. The primary outcome measure of our study was the correlation of
      the caval aorta (Ao) index with CVP, and the secondary outcome measures were the
      sensitivity and specificity of the caval Ao index. RESULTS: There was a positive
      correlation of inferior vena cava/Ao (IVC/Ao) index to CVP (R = 0.9 and
      significant P = 0.001*). The sensitivity and specificity of the IVC/Ao index were
      measured to predict the CVP. A CVP <=7 cm H2O correlated with IVC/Ao index 0.8 +/
      0.3 mean +/- standard deviation (SD) (sensitivity 0.93, specificity 0.66), a CVP
      of 8-12 cm H2O correlated with IVC/Ao index 1.5 +/- 0.2 mean +/- SD (sensitivity
      0.96, specificity 0.42), and a CVP >12 cm H2O correlated with IVC/Ao index 1.8 +/
      0.07 mean +/- SD (sensitivity 0.93, specificity 0.58). CONCLUSION: Sonographic
      caval Ao index is useful for the evaluation of preoperative and intraoperative
      volume status, especially in major surgeries with marked fluid shift or blood
      loss and had the advantage of being noninvasive, safe, quick, and easy technique
      with no complications.

PMID- 27051367
TI  - Evaluation of Acute Physiology and Chronic Health Evaluation II and sequential
      organ failure assessment scoring systems for prognostication of outcomes among
      Intensive Care Unit's patients.
AB  - CONTEXT: Acute Physiology and Chronic Health Evaluation II (APACHE II) and
      sequential organ failure assessment (SOFA) are of the most validated and
      prevalent general scoring systems over the world. AIMS: The aim of the current
      study was to evaluate APACHE II and SOFA ability in predicting the outcomes
      (survivors, nonsurvivors) in surgical and medical Intensive Care Unit (ICU).
      SETTING AND DESIGN: This was an observational and prospective study of 300
      consecutive patients admitted in surgical and medical ICU during a 6-month
      period. MATERIALS AND METHODS: APACHE II and SOFA scores and demographic
      characteristics were recorded for each patient separately in the first admission
      24 h. STATISTICAL ANALYSIS USED: Receiver operator characteristic (ROC) curves,
      Hosmer-Lemeshow test, and logistic regression were used in the statistical
      analysis (95% confidence interval). RESULTS: Data analysis showed a significant
      statistical difference in APACHE II and SOFA scores between survivor and
      nonsurvivor patients (P < 0.0001, P = 0.001; respectively). The discrimination
      power was acceptable for APACHE II and poor for SOFA (area under ROC [AUC] curve:
      73.7% (standard error [SE]: 3.2%), 63.4% [SE: 3.6%]; respectively). The
      acceptable calibration was seen just for SOFA (chi(2) = 11.018, P = 0.051).
      CONCLUSIONS: Both APACHE II and SOFA showed good predictive accuracy for results
      in surgical and medical ICUs; however, the SOFA is the choice to select, because
      of being simpler and easier to record data.

PMID- 27051369
TI  - Acoustic puncture assist device: A novel technique to identify the epidural
      space.
AB  - BACKGROUND: Acoustic puncture assist device (APAD) is designed to detect and
      signal the loss of resistance during the epidural procedure. We aimed to evaluate
      this device in terms of successful identification of the epidural space and the
      incidence of accidental dural puncture. PATIENTS AND METHODS: Following
      Institutional Review Board approval and written informed consent obtained from
      all patients, 200 adult patients (107 males) American Society of
      Anesthesiologists I-III who underwent lower limb orthopedic surgery under lumbar
      epidural anesthesia using APAD were enrolled in the study. APAD system was
      connected to the epidural needle using normal saline prefilled extension tube.
      Numbers of successful epidural attempts and accidental dural tap were documented.
      RESULTS: The mean values of the depth of epidural space and the time to perform
      epidural puncture were 5.8 +/- 1.0 cm and 3.3 +/- 1.4 min, respectively. In 63%
      of patients, epidural puncture was successful from the first attempt and in 1% it
      was successful from the fourth attempt. Epidural anesthesia by APAD was
      successful in 198 cases (99 %). Dural tap occurred in 2 cases (1%). CONCLUSIONS:
      Using APAD, the success of identifying the epidural space was high and reliable.

PMID- 27051370
TI  - The correlation between body mass index, limb circumferences and blood pressure
      cuff fit in bariatric surgical patients.
AB  - INTRODUCTION: The purpose of this study was to determine the correlation between
      body mass index (BMI) and upper and lower arm as well as lower leg circumferences
      and the frequency of correct blood pressure (BP) cuff fit. We explored
      recommendations for the most likely BP cuff size and location for the three BMI
      categories. MATERIALS AND METHODS: Following IRB approval we retrospectively
      analyzed a research database of bariatric surgical patients with a BMI of >=40
      kg/m(2). Data included patients' characteristics, upper and lower arm as well as
      lower leg circumferences. Patients were divided into three groups based on BMI
      (kg/m(2), Group I: <45, Group II: 45-55, and Group III: >55). Appropriate cuff
      fit using a standard or large adult BP cuff (CRITIKON((r)), GE Healthcare,
      Waukesha, Wisconsin, USA) on the upper and lower arm, and lower leg was
      determined. We analyzed the percent proportion of proper cuff fit for cuff sizes
      and locations between groups using appropriate nonparametric testing. RESULTS:
      Limb circumference correlated significantly with BMI (P = 0.01), and the upper
      arm correlated most closely (r = 0.76). A standard adult BP cuff on the lower arm
      fit properly in >90% and >80% and in Groups I and II, respectively. A large cuff
      on the lower arm was appropriate in 87% of Group III. In two participants, a
      large cuff fit properly on the lower leg. DISCUSSION: Limb circumference
      significantly correlated with BMI. Recommendations for proper cuff fit in
      different BMI categories can be made.

PMID- 27051371
TI  - Adding magnesium sulfate to bupivacaine in transversus abdominis plane block for
      laparoscopic cholecystectomy: A single blinded randomized controlled trial.
AB  - INTRODUCTION AND AIM: Use of transversus abdominis plane block (TAP) in the
      management of postoperative pain after the laparoscopic cholecystectomy (LC) has
      been a common anesthetic practice. This study evaluates the effect of adding
      magnesium sulfate to bupivacaine in TAP block in LC regarding postoperative
      analgesia and analgesic consumption. PATIENTS AND METHODS: Ninety patients of
      American Society of Anesthesiologists I and II was divided into three groups:
      Control group (C group, n = 30), bupivacaine group (B group, n = 30), bupivacaine
      magnesium group (M group, n = 30). RESULTS: M group showed better analgesic
      profile in the 1(st) postoperative day in the form of lower mean visual analog
      scale score (2.8 +/- 0.6 for C group, 2.1 +/- 0.5 for B group, 2.2 +/- 0.5 for M
      group, P < 0.001), longer duration of analgesia (7 +/- 2.8 h for C group, 16 +/-
      2.5 h for B group, 19 +/- 2.2 h for M group, P < 0.006), lower morphine
      consumption (2 +/- 0.1 mg for C group, 0.9 +/- 0.1 mg for B group, 0.5 +/- 0.1 mg
      for M group, P < 0.011). There was a significant lower incidence of postoperative
      nausea and vomiting (PONV) (32% for C group, 6% B group, 7% M group, P < 0.004).
      CONCLUSION: Adding MgSo4 as an adjuvant to bupivacaine in TAP block; during
      anesthesia for LC; improved postoperative analgesia in the form of increased
      duration, decreased analgesic requirements and PONV.

PMID- 27051372
TI  - A randomized placebo-controlled trial to evaluate a novel noninjectable
      anesthetic gel with thermosetting agent during scaling and root planing in
      chronic periodontitis patients.
AB  - AIM: To study the efficacy of a noninjectable anesthetic gel with a thermosetting
      agent in the reduction of pain during scaling and root planing (SRP) in untreated
      chronic periodontitis patients. MATERIALS AND METHODS: This study is a
      randomized, double-masked, split-mouth, placebo-controlled trial. Thirty patients
      were enrolled who underwent SRP in a split-mouth (right side/left side) manner.
      Before commencement of SRP, both quadrants on each side were isolated and had a
      randomized gel (either placebo or test gel) placed in the periodontal pockets for
      30 s. The pain was measured using numerical rating scale (NRS) and verbal rating
      scale (VRS). RESULTS: The median NRS pain score for the patients treated with the
      anesthetic test gel was 1 (range: 0-4) as opposed to 5 (range: 3-7) in the
      placebo treated patients. The mean rank of pain score using NRS in test gel was
      16.18 as compared to 44.82 in placebo treated sites. Hence, significant reduction
      in pain was found in test gel as compared to placebo using NRS (P < 0.001). The
      VRS showed that the majority of patients reported no pain or mild pain with a
      median of 1 as compared to placebo treated sites with a median of 2 suggestive of
      moderate pain. CONCLUSIONS: The NRS and VRS pain scores showed that the side
      treated with anesthetic gel was statistically more effective than the placebo in
      reducing pain during SRP.

PMID- 27051373
TI  - Cadaveric feasibility study on the use of ultrasound contrast to assess spread of
      injectate in the serratus anterior muscle plane.
AB  - BACKGROUND: The Serratus anterior muscle plane (SAP) block has recently been
      described for the purpose of perioperative pain management following cases of
      trauma and breast surgery. It might prove a safer alternative to the other
      regional thoracic paravertebral and central neuraxial blockade techniques. There
      are no descriptive cadaveric studies in the pre-existing literature to delineate
      the anatomical plane for this novel technique. The main objectives for our study
      were to examine the location of the Serratus anterior muscle belly, assess the
      efficacy of achieving adequate delineation of the muscle plane utilising
      ultrasound imaging with agitated water as the contrast agent, and finally, to
      observe the extent of the cepahlo-caudal spread of the injectate in the SAP.
      MATERIALS AND METHODS: Seven cadavers were studied. 20 mls of saline was injected
      into posterior axillary line (PAL) at the level of the 4-5(th) rib under
      ultrasound guidance. This was followed by injection of 10 mls of water with air
      (8 mls water and 2 mls of air). The presence of hyperechoic air bubbles in the
      fluid distended SAP (hypoechoic) area demonstrated the spread of water and air.
      RESULTS: In 36% of cadavers, fully formed Serratus Anterior muscle belly was
      identified at the midaxillary line (MAL), 14% in PAL, and remaining 50% between
      PAL and MAL. The lower most limit of air-water spread was identified at the
      subcostal margin. Cephalad spread of contrast was noted in 2(nd) intercostal
      space ICS (7%), 3(rd) ICS (71%), and 4(th) ICS (22%). CONCLUSION: This study
      describes that the serratus anterior muscle is well-formed near the PAL and the
      injectate spread can be determined with the help of agitated water contrast on
      ultrasound. Furthermore, there was variability in the cephalad spread of the
      injectate.

PMID- 27051374
TI  - Clinical performance of cuffed versus uncuffed preformed endotracheal tube in
      pediatric patients undergoing cleft palate surgery.
AB  - BACKGROUND: Uncuffed endotracheal tubes are commonly used in children but due to
      several decade preferred in paediatric oral surgery. Due to lack of conclusive
      evidences in this regard, we have conducted this study to compare post-operative
      morbidity following use of cuffed and uncuffed endotracheal tubes in paediatric
      patients undergoing cleft lip-palate surgery. METHODS: This randomised controlled
      trial was conducted on children aged 2 to 12 years.110 patients were allocated in
      two parallel groups using computer generated list of random numbers. Post
      operative extubation stridor, sore throat, time to first oral intake and
      regaining of normal voice were compared between two groups. RESULTS: The
      incidence of sore throat was significantly more (P value > 0.005) in patients of
      uncuffed group compared to cuffed group. The time to first oral intake and time
      to regain normal voice were significantly earlier in cuffed group compared to the
      other. CONCLUSION: With standard care, preformed cuffed ET tube has shown reduced
      incidence of post operative sore throat. Cuffed group has earlier oral intake and
      normal voice regain compared to uncuffed group.

PMID- 27051375
TI  - Knowledge and attitudes of Saudi intensive care unit nurses regarding oral care
      delivery to mechanically ventilated patients with the effect of healthcare
      quality accreditation.
AB  - INTRODUCTION: Ventilator-associated pneumonia is a major morbid outcome among
      intensive care unit (ICU) patients. Providing oral care for intubated patients is
      an important task by the ICU nursing staff in reducing the mortality and
      morbidity. The objectives of this study were to evaluate the attitudes and
      knowledge of ICU nurses regarding oral care delivery to critically ill patients
      in Saudi Arabian ICUs. The findings were further correlated to the presence of
      healthcare quality accreditation of the institution. MATERIALS AND METHODS: The
      nurses' knowledge, attitudes, and healthcare quality accreditation status of the
      hospital were recorded. Two hundred fifteen nurses conveniently selected from 10
      random hospitals were included in this study from Riyadh city, Saudi Arabia. This
      is a cross-sectional study in the form of a questionnaire. RESULTS: When
      comparing the knowledge of the participants to their level of education, there
      was no statistically significant difference between the two groups of nurses. The
      majority of the nurses agreed that the oral cavity is difficult to clean and that
      oral care delivery is a high priority for mechanically ventilated patients.
      Furthermore, there was no statistically significant difference in the attitudes
      between nurses working in accredited and nonaccredited hospitals. CONCLUSION: The
      presence of healthcare quality accreditation did not reflect any significance in
      attitudes or knowledge of the ICU nurses in regard to mechanically ventilated
      patients. Factors affecting oral care delivery should be evaluated on the
      personal and institutional level to achieve better understanding of them.

PMID- 27051376
TI  - Is it time for routine use of the retromolar fiberscope?
AB  - PURPOSE: This study aimed to determine the effectiveness, safety, and oral
      intubation time (IT) using a retromolar Bonfils fiberoptic scope compared with a
      conventional Macintosh laryngoscope. MATERIALS AND METHODS: Sixty patients (16-60
      years old, American Society of Anesthesiology I/II) scheduled for general
      anesthesia for elective ear-nose-throat and plastic surgery were randomly divided
      into a Bonfils group (Group B, n = 30) and a Macintosh group (Group M, n = 30).
      Exclusion criteria included Mallampati IV, thyromental distance <=4 cm, mouth <4
      cm, cervical spine problems, body mass index >35, sleep apnea, reflux
      esophagitis, coronary artery disease, intracranial vascular malformation,
      elevated intracranial pressure, bleeding disorders, allergies to planned drugs,
      and patient refusal. Mallampati scoring, mouth opening, and thyromental distance
      were used for airway assessment. The time needed for successful intubation (IT),
      number of attempts, number of failures, systolic (SBP), diastolic (DBP), mean
      blood pressure (MBP), heart rate (HR) and Oxygen saturation (O2) and damage to
      the lips, dentures, and pharyngeal or laryngeal structures were recorded.
      Continuous variables are presented as mean +/- standard deviation and categorical
      variables are presented as frequency and percentage. Chi-square tests and
      Student's t-tests were used to compare the groups. P < 0.05 was considered
      statistically significant. RESULTS: The groups were comparable regarding
      demographic data, preoperative airway parameters, IT, the number of attempts, O2,
      and the incidence of complications (P > 0.05). However, Bonfils intubation was
      associated with more stable HR, SBP, DBP and MBP (P < 0.05). CONCLUSION: The
      Bonfils fiberoptic scope is comparable to a Macintosh laryngoscope but assures
      better hemodynamic stability. In difficult cases, the Bonfils scope is a better
      choice because of its ability to navigate.

PMID- 27051377
TI  - Videolaryngoscopes for placement of double lumen tubes: Is it time to say goodbye
      to direct view?
AB  - The advances in thoracic procedures require optimum lung separation to provide
      adequate room for surgical access. This can be achieved using either a double
      lumen tube (DLT) or a bronchial blocker (BB). Most thoracic anesthesiologists
      prefer the use of DLT. However, lung separation in patients with potential
      difficult airway can be achieved using either BB through a single lumen tube or
      placement of a DLT over a tube exchanger or a fiberoptic bronchoscope. Numerous
      videolaryngoscopes (VL) have been introduced offering both optical and video
      options to visualize the glottis. Many studies reported improved glottis
      visualization and easier DLT intubation in patients with normal and potential
      difficult airway. However, these studies have a wide diversity of outcomes, which
      may be attributed to the differences in their designs and the prior experience of
      the operators in using the different devices. In the present review, we present
      the main outcomes of the available publications, which have addressed the use of
      VL-guided DLT intubation. Currently, there is enough evidence supporting using VL
      for DLT intubation in patients with predicted and unanticipated difficult airway.
      In conclusion, the use of VL could offer an effective method of DLT placement for
      lung separation in patients with the potential difficult airway. 

PMID- 27051378
TI  - Caudal anesthesia in a patient with peritonitis: Is it safe??
AB  - Neuraxial anesthesia combined with general anesthesia has become a widely
      accepted method of providing effective postoperative analgesia and decreasing
      intraoperative anesthetic needs in the pediatric population. In clinical
      practice, there still appears to be hesitancy for the use of a neuraxial
      technique (spinal or epidural) in patients at risk for bacteremia or with an on
      going systemic infection. However, evidence-based medicine lacks any data to
      support an increase in the risk of infectious complications following neuraxial
      anesthesia. We present two pediatric patients with intra-abdominal infectious
      processes who received caudal epidural blockade for postoperative operative
      analgesia. The use of neuraxial techniques in patients at risk for bacteremia is
      reviewed, evidence-based medicine regarding the risks of infection discussed, and
      the potential favorable effects of neuraxial blockade on the neurohumoral
      response to sepsis and the systemic inflammatory responses presented. 

PMID- 27051379
TI  - Maxillary tumor in a child: An expected case of difficult airway.
AB  - Craniofacial abnormalities in pediatric population fall under the category of
      expected case of difficult airway. We present here a case of large maxillary
      tumor in a 9-year-old girl where the relative difficulty was further compounded
      due to her noncooperation which was again expected from a child. Local anesthetic
      topicalization of airway followed by slow inhalational induction with gradually
      increasing sevoflurane, while maintaining her spontaneous breathing, we secured
      her airway using fiber optic bronchoscopy. The surgery and the extubation went
      uneventful. In conclusion a planned airway management using fiber optic
      bronchoscope after airway topicalization and sevoflurane induction is the ideal
      technique in an expected case of difficult pediatric airway. 

PMID- 27051380
TI  - Severe refractory hypertension during shoulder arthroscopy.
AB  - The use of epinephrine-containing saline irrigating solutions during arthroscopic
      shoulder surgery gained popularity after it was reported that the addition of
      epinephrine reduced bleeding and improved visualization without adverse
      cardiovascular effects. We share a case of a patient undergoing shoulder
      arthroscopy who received a standard intra-articular infusion of epinephrine
      containing normal saline (1 mcg/mL) and experienced severe hemodynamic
      consequences. 

PMID- 27051381
TI  - Managing diabetic ketoacidosis in pregnancy.

PMID- 27051382
TI  - Novel positioning solution for difficult tracheostomy.

PMID- 27051383
TI  - Rare cause of failure of central venous catheter insertion in a patient with end
      stage renal disease-septum in internal jugular vein.

PMID- 27051384
TI  - Anesthetic management of an adolescent with congenital glossopharyngeal web.

PMID- 27051385
TI  - Airtraq laryngoscope: Embracing video laryngoscopy.

PMID- 27051386
TI  - Pharyngeal tear during gastric calibration tube insertion for laparoscopic sleeve
      gastrectomy.

PMID- 27051387
TI  - Anesthetic management of a neonate with Beckwith-Wiedemann syndrome posted for
      repair of exomphalos.

PMID- 27051388
TI  - If Chemotherapy Is Indicated, Give the Optimal Regimen!

PMID- 27051389
TI  - Adjuvant Dose-Dense Chemotherapy in Breast Cancer: Standard of Care in High-Risk
      Patients.
AB  - Meta-analyses persistently confirm the superiority of dose-dense chemotherapy in
      comparison with standard chemotherapy. In contrast, individual studies have shown
      conflicting results. These may be explained by different risk profiles of the
      treated patient populations. Some trials show a significant advantage in disease
      free survival (DFS) and overall survival (OS) in the estrogen receptor (ER)
      negative population only, whereas trials with high-risk populations like GIM-2
      (Gruppo Italiano Mammella) and AGO-iddETC (Arbeitsgemeinschaft Gynakologische
      Onkologie, intense dose-dense epirubicin, paclitaxel, and cyclophosphamide) show
      a significant superiority in DFS and OS for both, ER-negative and ER-positive
      patients even after 7 and 10 years, respectively, of follow-up. In contrast, the
      10-year follow-up data of the E1199/Intergroup trial no longer showed any
      superiority of weekly paclitaxel for ER-positive/HER2-negative patients;
      superiority was observed in the triple-negative subgroup only. Although a direct
      head-to-head comparison is missing, iddETC or 4 cycles each of dose-dense
      epirubicin/cyclophosphamide followed by paclitaxel are the preferred adjuvant
      regimens for patients at risk. Patients with >= 4 positive lymph nodes should
      preferentially be treated with iddETC. 

PMID- 27051391
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000368330.]. 

PMID- 27051390
TI  - Neoadjuvant Dose-Dense and Dose-Intensified Chemotherapy in Breast Cancer -
      Review of the Literature.
AB  - Dose-dense chemotherapy in the adjuvant and neoadjuvant setting has been
      intensively examined over the past few decades, and even seems to have become a
      standard regimen in certain subgroups of patients with increased risk of relapse.
      Nevertheless, there are conflicting data regarding the absolute benefit of this
      regimen, especially in the neoadjuvant setting. Pathological complete response
      (pCR) is used as a surrogate marker for disease-free and overall survival. Meta
      analyses have recently questioned the use of pCR as a generalized prognostic tool
      for all subgroups, but also determined a correlation between treatment effects on
      the surrogate outcome and the treatment effect on the clinical outcome in the
      cohort of patients receiving dose-dense chemotherapy. The present paper gives an
      overview of the definitions of dose-dense and dose-intensified chemotherapy
      regimens and of the literature for neoadjuvant dose-dense, dose-intensified
      studies, and summarizes the outcome of these studies. 

PMID- 27051392
TI  - Dose-Dense Chemotherapy in Metastatic Breast Cancer: Shortening the Time Interval
      for a Better Therapeutic Index.
AB  - Despite the advancement of targeted therapies in metastatic breast cancer,
      chemotherapy is still of pivotal importance. The concept of dose density is known
      to increase the efficacy of chemotherapy. In metastatic disease, preservation of
      the quality of life is equally important. Because of this, weekly regimens are a
      cornerstone in metastatic disease. Taxanes like paclitaxel or nab-paclitaxel as
      well as antracyclines are often used in palliative treatment. Further advances to
      increase dose density have led to the concept of daily metronomic schedules with
      oral chemotherapeutic drugs like cyclophosphamide, capecitabine, or vinorelbine.
      Metronomic chemotherapy affects tumor angiogenesis and also weakens
      immunosuppressive regulatory T cells, promoting better control of tumor
      progression. Weekly or daily dose-dense regimens are a reasonable compromise
      between efficacy and toxicity to improve the therapeutic index. This is most
      important for the treatment of chronic disease where palliation and preservation
      of quality of life are vital. 

PMID- 27051393
TI  - Evaluation of Social Support, Quality of Life, and Body Image in Women with
      Breast Cancer.
AB  - BACKGROUND: This study was aimed at comparing the quality of life, body image,
      and perceived social support in women with breast cancer surgery. PATIENTS AND
      METHODS: Patients receiving breast-conserving surgery (BCS) (n = 72), mastectomy
      alone (n = 44), and mastectomy with breast reconstruction (n = 41) were evaluated
      using the European Organization for Research and Treatment of Cancer Quality of
      Life Questionnaire (EORTC QLQ-C30), the EORTC Breast Cancer Module (QLQ-BR23),
      the Body Image Scale (BIS) and the Multidimensional Scale of Perceived Social
      Support (MSPSS). RESULTS: The results indicated that the BCS group had a better
      body image compared with the other 2 groups and better role functioning compared
      with the mastectomy-alone group. In the reconstruction group, body image
      correlated with perceived social support, especially from family and significant
      others. CONCLUSION: These results suggest that a positive perception of a
      supportive social network can help women with breast reconstruction to better
      cope with the psychological effects of surgery on their body image.

PMID- 27051394
TI  - Diagnostic Accuracy and Impact on Management of Ultrasonography-Guided Fine
      Needle Aspiration to Detect Axillary Metastasis in Breast Cancer Patients: A
      Prospective Study.
AB  - BACKGROUND: The axillary nodal status is essential to determine the stage of
      disease at diagnosis. Our aim was to prospectively assess the diagnostic accuracy
      of ultrasonography-guided fine-needle aspiration (US-FNA) for the detection of
      metastasis in axillary lymph nodes in patients with breast cancer (BC) and its
      impact on the therapeutic decision. MATERIALS AND METHODS: Ultrasonography (US)
      was performed in 407 axillae of 396 patients who subsequently underwent surgery.
      US-FNA was conducted when lymph nodes were detected by US. Axillary dissection
      (AD) was performed when US-FNA was positive for metastasis. Patients with
      negative US-FNA and breast tumors of 30 mm in size were candidates for selective
      sentinel lymph node biopsy (SLNB). The anatomopathological results of AD or SLNB
      were used as reference tests. RESULTS: Lymph nodes were detected by US in 207
      (50.8%) axillae. Of these, US-FNA was performed on 180 (86.9%). 94 axillae
      (52.2%) were positive for carcinoma and 79 women received AD. US-FNA had 77.5%
      sensitivity, 100% specificity, 100% positive predictive value, 69.3% negative
      predictive value, and 85.1% diagnostic accuracy. US-FNA avoided SLNB in 18.1% of
      patients who underwent AD. CONCLUSIONS: Axillary US-FNA is an accurate technique
      in the staging of patients with BC. It allows reducing the number of SLNB and,
      when positive, offers a fast and useful tool.

PMID- 27051395
TI  - Manual Lymphatic Drainage after Subepidermal Tracer Injection Optimizes Results
      of Sentinel Lymph Node Labeling in Primary Breast Cancer.
AB  - INTRODUCTION: Our aim was to assess the practicability and reliability of a novel
      labeling regime for axillary sentinel lymph nodes (SLNs) in early breast cancer.
      METHODS: 362 patients with early breast cancer (bilateral in 9 cases, giving a
      total of 371 cases) underwent intradermal radio tracer injection with
      simultaneous manual lymphatic drainage. SLN biopsy was performed within 24 h. For
      retrospective analysis, data were extracted from patient's records. RESULTS: At
      least 1 SLN was detected intraoperatively in 369 cases (99.5%, range 1-9 nodes).
      This node was metastatic in 88 and unaffected in 281 cases. Coincidentally
      removed but unlabeled lymph nodes were affected in 3 cases in which the SLN was
      unaffected (3/153 = 2%). In all cases, on histological evaluation, tissue removed
      as SLN contained lymph nodes. After a period of 69.5 months (median 1.7-115.8
      months), no axillary recurrences were observed in 213 patients. CONCLUSION:
      Manual lymphatic drainage is a simple technique that leads to an extremely high
      pick-up rate of axillary SLNs after subepidermal radio tracer injection. If
      unaffected, this node correctly predicts nodal-negative disease in 98% of cases
      studied.

PMID- 27051396
TI  - Risk Factors for Arm Lymphedema in a Cohort of Breast Cancer Patients Followed up
      for 10 Years.
AB  - BACKGROUND: The etiology of lymphedema is multifactorial, and definition criteria
      of lymphedema, its limitation, and follow-up must be considered in studies
      related to risk factors. The aim of this study is to evaluate risk factors
      related to arm lymphedema in a cohort study with a long follow-up. PATIENTS AND
      METHODS: The study was performed in 622 breast cancer patients. The main endpoint
      reported was the presence of clinical lymphedema reported in medical records.
      Univariate and multivariate regression analyses were performed to identify
      factors related to lymphedema. RESULTS: 66.4% of the patients were submitted to
      mastectomy, 88.4% to level III axillary lymphadenectomy, 34.9% to radiotherapy in
      the supraclavicular fossa, and 4.3% to axillary radiotherapy. The mean follow-up
      was 96.7 months. 45 patients (7.2%) developed lymphedema, of which 82.2% had
      developed lymphedema at 60 months. Univariate regression analysis showed that
      supraclavicular radiotherapy, adjuvant/palliative chemotherapy, >= 15 lymph nodes
      dissected, and axillary surgery increase the lymphedema rate by 1.87, 2.28, 2.03,
      and 6.17, respectively. Adjusted multivariate regression analysis showed that the
      combination of axillary dissection and number of lymph nodes dissected was the
      main factor related to lymphedema (p = 0.017). CONCLUSION: In the pre-sentinel
      era, axillary dissection and the number of lymph nodes resected are related to 10
      year lymphedema.

PMID- 27051397
TI  - A Scoring System to Predict Arm Lymphedema Risk for Individual Chinese Breast
      Cancer Patients.
AB  - BACKGROUND: Lymphedema (LE) is recognized as a common complication after axillary
      lymph node dissection (ALND). Numerous studies have attempted to identify risk
      factors for LE. However, it is difficult to predict the probability of LE for an
      individual patient. The purpose of this study was to construct a scoring system
      for predicting the probability of LE after ALND for Chinese breast cancer
      patients. PATIENTS AND METHODS: 358 breast cancer patients were surveyed and
      followed for 12 months. LE was defined by circumferential measurement. Univariate
      and multivariate logistic regression analyses were used to screen risk factors of
      LE. Based on this, beta-coefficient of each risk factor was translated into a
      prognostic score and the scoring system was constructed. The area under the
      receiver operating characteristic curve (AUC) and calibration were calculated as
      an index for the predictive value of the scoring system. The model was internally
      validated using bootstrapping techniques. RESULTS: The incidence rate of LE was
      31.84%. Variables associated with LE and their corresponding score in the scoring
      system were: the level of ALND (level I = 0, level II = 1, level III = 2),
      history of hypertension (yes = 1, no = 0), surgery on dominant arm (yes = 1, no =
      0), radiotherapy (yes = 2, no = 0), and surgical infection/seroma/early edema
      (yes = 2, no = 0). The probability of LE was predicted according to the total
      risk scores. The system had good discrimination, with an AUC at 0.877. If a cut
      off value of 3 was used, the sensitivity was 81.20% and the specificity was
      80.90%. An individual whose total risk score was higher than 3 was recognized as
      being at risk for LE. On internal validation, the bootstrap-corrected predictive
      accuracy was 0.798. The model demonstrated excellent calibration in the
      development set and internal validation. CONCLUSIONS: Our scoring system could be
      a simple and easy tool for physicians to estimate the risk of LE.

PMID- 27051398
TI  - First Report of Pyoderma Gangrenosum after Surgery of Breast Cancer-Related
      Lymphedema with Transfer of Vascularized Free Lymph Nodes of the Groin and
      Simultaneous DIEP Flap.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is a rare cutaneous ulcerative disease that
      does not respond to antibiotics and worsens with surgical manipulation. This is
      the first report in the literature revealing that this disease complicates total
      microsurgical breast reconstruction associated with the transfer of free lymph
      nodes. CASE REPORT: We report the case of a female patient who underwent left
      breast microsurgical reconstruction with a deep inferior epigastric perforator
      (DIEP) flap and simultaneous transfer of vascularized free lymph nodes for the
      surgical treatment of secondary left upper-limb lymphedema, and who developed a
      severe PG of both the skin of the flap and the donor zone on postoperative day 7.
      After exclusion of other etiologies, treatment with high-dose corticosteroids and
      topical zinc sulfate was initiated. The flap was salvaged and breast cancer
      related lymphedema (BCRL) surgery was definitively effective despite the PG.
      CONCLUSIONS: PG should be considered in the differential diagnosis of progressive
      cutaneous ulcers following surgical interventions, once infectious and ischemic
      etiologies have been excluded. Early initiation of immunosuppressive treatment
      can lead to preservation of the initial flap and function of the transferred
      lymph nodes in the case of microsurgical breast reconstruction with associated
      lymph node transfer.

PMID- 27051399
TI  - ABC3 Consensus: Assessment by a German Group of Experts.
AB  - The Advanced Breast Cancer Third International Consensus Conference on the
      diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal,
      on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment
      of metastatic breast cancer (stage IV), as it was 4 years ago at the first
      consensus meeting (ABC1). A matter of particular interest was the patients'
      perspective. Thus, patient-relevant issues were addressed by the consensus
      discussions, such as those on treatment goals, quality of life, care of long-term
      survivors ('survivorship issues'), and coping with disease-related symptoms and
      the side effects of treatment. Further important issues on the agenda were the
      use of standardized instruments for the assessment of individual treatment
      success ('patient-reported outcome measures') and the evaluation of the benefit
      of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude
      of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally
      advanced breast cancer had already been discussed 2 years earlier at the ABC2
      Consensus and were not dealt with in the framework of this year's ABC3 Consensus.
      With regard to country-specific peculiarities, which unavoidably found their way
      into the ABC Consensus, a working group of German breast cancer experts commented
      on the voting results of the ABC panelists. As for the past consensus, the group
      specially considered the German guidelines for the diagnosis and treatment of
      breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of
      Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for
      everyday therapy in Germany. 

PMID- 27051400
TI  - Update on Female Cancer in Africa: The AORTIC Conference 2015, Morocco.

PMID- 27051401
TI  - Hemorrhagic Transformation in Patients with Cerebral Infarction Referred to a
      Rehabilitation Hospital.
AB  - PURPOSE: The aim of our study was to investigate the presenting conditions of
      patients with hemorrhagic transformation (HT), the frequency of HT and its
      treatments at a rehabilitation hospital. SUBJECTS AND METHODS: 165 patients with
      cerebral infarctions transferred to our rehabilitation hospital during the study
      period were enrolled. HT was diagnosed by two stroke specialists using computed
      tomography (CT) at the time of transfer to our rehabilitation hospital and other
      imaging data from previous consultations. Neurological status, activities of
      daily living, administered agents, patient age, duration from stroke onset to
      transfer and length of hospital stay were examined. RESULTS: 30 of the 165
      patients (18.2%) were diagnosed with HT. Decreased activities of daily living at
      admission and discharge as well as longer hospitalization stays were more
      prevalent in HT patients than in those without HT. We did not change antiplatelet
      or anticoagulant agents, but continued rehabilitation over a defined period while
      monitoring blood pressure; we confirmed with CT that the patients' physical
      conditions did not deteriorate. CONCLUSION: With careful symptom and CT
      monitoring over a defined period, rehabilitation can be continued in patients who
      develop HT at the time of transfer to a rehabilitation hospital in the acute
      phase of cerebral infarction.

PMID- 27051403
TI  - Main Trunk and Division Middle Cerebral Artery Occlusions: Differences in
      Recanalization Times, Number of Stent Retriever Passes and Clinical Outcomes: A
      Single-Center Experience.
AB  - BACKGROUND AND PURPOSE: In this article, we present our experience with the
      recanalization of the middle cerebral artery (MCA), we hypothesize that there are
      higher rates of recanalization with fewer stent retriever passes and better
      clinical outcomes in patients with division MCA occlusions. A more complex
      anatomy at the bifurcation may prevent a faster recanalization in main trunk MCA
      occlusions. METHODS: We retrospectively identified consecutive patients admitted
      with MCA occlusions who underwent mechanical thrombectomy using stent retrievers.
      We categorized patients into division MCA and main trunk MCA occlusions based on
      angiography. Variables were compared between the groups. We further analyzed
      patients with trunk MCA occlusions to identify reasons for delays in
      recanalization. RESULTS: There were 32 MCA occlusions that underwent mechanical
      thrombectomy and eligible for the analysis during the study period. Of those, 11
      were main trunk MCA occlusions. Univariate analysis disclosed a trend toward a
      lower GP-to-recanalization time (p = 0.05) and a lower number of passes required
      for recanalization in division MCA occlusions. However, there was a significantly
      better outcome in patients with division MCA occlusion after multivariate
      analysis. Analyzing main trunk MCA occlusion data, we found that the need for
      more than one pass to achieve recanalization led to a trend toward a longer GP-to
      recanalization time and a worse outcome. When the stent was placed in the
      dominant division, the chances of recanalization were significantly higher.
      CONCLUSIONS: Division MCA occlusions have higher recanalization rates with fewer
      stent retriever passes and better clinical outcomes than main trunk MCA
      occlusions, likely due to a more favorable anatomy. Measures like placing the
      stent retriever in the dominant division may decrease recanalization times and
      improve clinical outcomes in main trunk MCA occlusions.

PMID- 27051402
TI  - Inadvertent Stent Retriever Detachment: A Multicenter Case Series and Review of
      Device Experience FDA Reports.
AB  - Mechanical thrombectomy using retrievable stents or stent retriever devices has
      become the mainstay of intra-arterial therapy for acute ischemic stroke. The
      recent publication of a series of positive trials supporting intra-arterial
      therapy as standard of care for the treatment of large vessel occlusion will
      likely further increase stent retriever use. Rarely, premature stent detachment
      during thrombectomy may be encountered. In our multicenter case series, we found
      a rate of detachment of less than 1% (n = 7/1,067), and all were first-generation
      Solitaire FR devices. A review of the US Food and Drug Administration database of
      device experience yielded 90 individual adverse reports of detachment. There were
      82, 1 and 7 detachments of Solitaire FR (first generation), Solitaire FR2 (second
      generation) and Trevo devices, respectively. We conclude with a brief overview of
      the technical and procedural considerations which may be helpful in avoiding this
      rare complication. 

PMID- 27051404
TI  - A Concealed Intracranial Aneurysm Detected after Recanalization of an Occluded
      Vessel: A Case Report and Literature Review.
AB  - BACKGROUND: Based on the results of several randomized controlled trials, acute
      endovascular thrombectomy is strongly recommended for patients with acute
      ischemic stroke due to large artery occlusion (LAO). The incidence of an
      intracranial aneurysm has been reported to be approximately 5% in the general
      population. Therefore, the possibility of the coincidence of LAO and an
      intracranial aneurysm at the distal part of an occluded vessel should be
      considered. SUMMARY: A 74-year-old female patient presented with the sudden onset
      of consciousness disturbance and left-sided weakness. Neuroimages demonstrated an
      acute infarction due to right middle cerebral artery occlusion. The occlusion was
      successfully treated, and an aneurysm was incidentally detected at the occluded
      artery. We reviewed the literature and identified 11 cases in 8 reports, which
      were similar to our case. Among the 11 cases, aneurysms ruptured during
      endovascular therapy in 2 cases. In the present report, we discussed the
      prediction of concealed aneurysms and avoidance of their rupture during
      endovascular intervention. KEY MESSAGE: The presence of an aneurysm concealed
      behind an embolus should be carefully assessed on preoperative and intraoperative
      neuroimages. The important findings for suspecting such an aneurysm are a
      hyperdense nodular sign on preoperative computed tomography and unusual motion of
      the microwire during the endovascular intervention. Even if there is no finding
      indicative of an aneurysm, the catheter and thrombectomy devices should be more
      carefully advanced than usual, especially at the common sites of aneurysms, and
      the devices should be appropriately chosen.

PMID- 27051405
TI  - Management of Bilateral Carotid Occlusive Disease.
AB  - BACKGROUND: Symptomatic bilateral internal carotid occlusive disease is a rare
      but potentially devastating entity. Medical therapy alone is associated with high
      rates of mortality and recurrent stroke. The optimal management of this disease
      remains poorly understood. METHODS: A retrospective review of a prospectively
      maintained database was conducted for patients who presented with an acute stroke
      in the setting of bilateral carotid occlusive disease between May and October
      2013. RESULTS: We identified 3 patients. The admission National Institutes of
      Health Stroke Scale score ranged from 4 to 7. All patients had small- to moderate
      sized infarcts in the anterior circulation on presentation. Angiography confirmed
      bilateral internal carotid occlusions with collateral filling via the posterior
      communicating artery and retrograde filling via external carotid artery supply to
      the ophthalmic artery. All patients were initially managed with permissive
      hypertension and anticoagulation followed by carotid angioplasty and stenting. At
      1-year follow-up, all patients demonstrated a modified Rankin scale score of 0-1.
      CONCLUSIONS: Carotid stenting may be a safe and effective therapy for patients
      presenting with symptomatic bilateral carotid occlusions.

PMID- 27051406
TI  - Whole-Brain Computed Tomographic Perfusion Imaging in Acute Cerebral Venous Sinus
      Thrombosis.
AB  - BACKGROUND: Acute cerebral venous sinus thrombosis (VST) can be difficult to
      diagnose because of its diverse clinical presentation. The utility of perfusion
      imaging for diagnosing VST is not well understood. SUMMARY: We retrospectively
      reviewed cases of acute VST in patients who underwent whole-brain (320-detector
      row) computed tomographic (CT) perfusion imaging in combination with
      craniocervical CT venography. Perfusion maps that were analyzed included cerebral
      blood volume (CBV), cerebral blood flow (CBF), mean transit time, and time to
      peak. Among the 10 patients with acute VST included in this study, 9 had
      perfusion abnormalities. All perfusion abnormalities were localized in areas
      adjacent to the occluded sinus and did not match typical anterior or posterior
      circulation arterial territories. Bilateral perfusion deficits were seen in 4
      cases. In 2 cases, parenchymal hemorrhage was diagnosed on noncontrast CT
      imaging; in those cases, focal CBV and CBF were reduced. KEY MESSAGES: Whole
      brain CT perfusion imaging with 320-detector-row scanners can further assist in
      establishing the diagnosis of VST by detecting perfusion abnormalities
      corresponding to venous and not arterial territories. CT perfusion could assist
      in the differentiation between focal reversible changes, such as those caused by
      vasogenic edema, and irreversible changes due to infarction.

PMID- 27051407
TI  - The Use of Aspiration Catheter Systems for Embolic Protection during Intracranial
      Vertebral Artery Angioplasty and Stenting.
AB  - BACKGROUND: Posterior circulation strokes comprise approximately 20-25% of all
      strokes of ischemic origin. Strokes affecting this area carry a significantly
      higher risk for subsequent stroke or death as compared to anterior circulation
      strokes. Embolic protection device (EPD) use for carotid artery stenosis has
      translated into percutaneous interventions of proximal vertebral artery (VA)
      stenosis. However, the use of EPDs when treating intracranial lesions has yet to
      be studied and may not be feasible as the vessel caliber is frequently smaller
      than in existing devices. OBJECTIVE: The aim of this study is to describe a
      proximal aspiration technique used during the treatment of intracranial VA and
      basilar artery (BA) atherosclerotic disease. METHODS: Proximal embolic protection
      was utilized during the treatment of intracranial VA/BA stenosis with angioplasty
      and stenting in patients with medically refractory disease. RESULTS: Three
      patients with severe symptomatic posterior circulation stenosis refractory to
      medical management were treated with angioplasty and stenting utilizing proximal
      aspiration. Pre- and post-treatment angiograms and MRIs were compared. Treated
      vascular stenoses were significantly improved, without new neurological deficits
      or ischemic injury identified on imaging. CONCLUSIONS: The proposed technique of
      proximal embolic protection may help overcome the challenge of embolus
      propagation inherent to the treatment modality that was encountered during the
      treatment of intracranial VA/BA stenosis.

PMID- 27051408
TI  - Prognostic Value of the 24-Hour Neurological Examination in Anterior Circulation
      Ischemic Stroke: A post hoc Analysis of Two Randomized Controlled Stroke Trials.
AB  - BACKGROUND: Early prognostication of long-term outcomes following ischemic stroke
      can facilitate medical decision-making. We hypothesized that the 24-hour National
      Institute of Health Stroke Scale (NIHSS) predicts 3-month clinical outcomes in
      anterior circulation stroke. METHODS: Secondary analyses of the Interventional
      Management of Stroke 3 (IMS3) and intravenous tissue plasminogen activator (IV
      tPA) for acute ischemic stroke [National Institute of Neurological Diseases and
      Stroke (NINDS) IV tPA] trials were performed. In participants with documented 24
      hour NIHSS and 3-month Modified Rankin Scale (mRS), the predictive power of the
      24-hour NIHSS and 24-hour NIHSS improvement for 3-month outcomes [mRS 0-2 and
      Barthel Index (BI) >=95] was assessed. Percentages of good outcome (mRS 0-2 or BI
      >=95) at 3, 6, and 12 months and mean quality of life (EQ5DTM) index at 3 months
      across 24-hour NIHSS quartiles were compared. RESULTS: The majority of the study
      participants were included (IMS3 n = 587/656, NINDS IV tPA n = 619/624). The 24
      hour NIHSS was correlated with 3-month mRS (R = 0.73) with excellent predictive
      power for mRS 0-2 [area under the curve (AUC) = 0.91] and BI >=95 (AUC = 0.9) in
      both cohorts. A model with the 24-hour NIHSS alone correctly classified 82-84% of
      patients in both cohorts. The percentages of good outcomes at 3-12 months across
      24-hour NIHSS quartiles were similar in both cohorts. mRS 0-2 was achieved by
      75.6-77.7% of patients with 24-hour NIHSS <=11 but by only 1.4-3.6% with 24-hour
      NIHSS >=20. The EQ5D index at 3 months varied among NIHSS 0-4 (mean 0.86 +/-
      0.16), 5-11 (0.77 +/- 0.18), and 12-19 (0.59 +/- 0.26) quartiles. CONCLUSIONS:
      The 24-hour NIHSS strongly predicts long-term stroke outcomes and is associated
      with quality of life. Its easy availability, reliability, and validity support
      its use as an early prognostic marker and surrogate of clinical outcome in
      ischemic stroke.

PMID- 27051409
TI  - Symptomatic Infratentorial Thrombosed Developmental Venous Anomaly: Case Report
      and Review of the Literature.
AB  - BACKGROUND: Developmental venous anomalies (DVAs) are variations of normal
      transmedullary veins draining white and gray matter. In the vast majority of
      cases, DVAs are diagnosed incidentally and should be considered as benign
      entities. In extremely rare circumstances, DVAs may become symptomatic due to
      mechanical or flow-related etiologies. Thrombosis of the collector vein of a DVA
      is a rare type of a flow-related complication with only 29 cases reported in the
      literature, the majority of which are supratentorial. Infratentorial thrombosed
      DVAs are thus extremely rare and the few cases reported have typically caused
      symptoms due to venous ischemic infarctions. SUMMARY: We report a case of an
      infratentorial DVA with a thrombosed drainage vein in a patient with
      nonhemorrhagic, noninfarcted venous congestive edema, which was successfully
      treated with high-dose glucocorticoids and short-term anticoagulation. We review
      the pertinent venous anatomy of the posterior fossa as well as the literature of
      symptomatic infratentorial thrombosed DVAs. KEY MESSAGE: The presented case of an
      infratentorial thrombosed DVA with cerebellar and pontine venous congestive edema
      is extremely rare. A working knowledge of posterior fossa venous anatomy and
      possible pathomechanisms responsible for the rarely symptomatic lesion will aid
      in the timely and efficacious treatment of such lesions.

PMID- 27051410
TI  - Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and
      Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke
      Standards Committee of the Society of Vascular and Interventional Neurology
      (SVIN).
AB  - Five landmark multicenter, prospective, randomized, open-label, blinded end point
      clinical trials have recently demonstrated significant clinical benefit of
      endovascular therapy with mechanical thrombectomy in acute ischemic stroke (AIS)
      patients presenting with proximal intracranial large vessel occlusions. The
      Society of Vascular and Interventional Neurology (SVIN) appointed an expert
      writing committee to summarize this new evidence and make recommendations on how
      these data should guide emergency endovascular therapy for AIS patients. 

PMID- 27051411
TI  - Lower Intraprocedural Systolic Blood Pressure Predicts Good Outcome in Patients
      Undergoing Endovascular Therapy for Acute Ischemic Stroke.
AB  - BACKGROUND: It is unknown if intraprocedural blood pressure (BP) influences
      clinical outcomes and what BP parameter best predicts outcomes in acute ischemic
      stroke (AIS) patients who undergo intra-arterial therapy (IAT) for emergent large
      vessel occlusion. METHODS: We retrospectively reviewed 147 patients who underwent
      IAT for anterior circulation AIS from January 2008 to December 2012 at our
      institution. Baseline demographics, stroke treatment variables, and detailed
      intraprocedural hemodynamic variables were collected. RESULTS: The entire cohort
      consisted of 81 (55%) females with a mean age of 66.9 +/- 15.6 years and a median
      National Institutes of Health Stroke Scale (NIHSS) score of 16 (IQR 11-21).
      Thirty-six (24.5%) patients died during hospitalization, 25 (17%) achieved a 30
      day modified Rankin Scale score of 0-2, and 24 (16.3%) suffered symptomatic
      parenchymal hematoma type 1/2 hemorrhage. Patients who achieved a good outcome
      had a significantly lower admission NIHSS score, a higher baseline CT ASPECTS
      score, and a lower rate of ICA terminus occlusions. Successful recanalization was
      more frequent in the good-outcome group, while symptomatic hemorrhages occurred
      only in poor-outcome patients. The first systolic BP (SBP; 146.5 +/- 0.2 vs.
      157.7 +/- 25.6 mm Hg, p = 0.042), first mean arterial pressure (MAP; 98.1 +/-
      20.8 vs. 109.7 +/- 20.3 mm Hg, p = 0.024), maximum SBP (164.6 +/- 27.6 vs. 180.9
      +/- 18.3 mm Hg, p = 0.0003), and maximum MAP (125.5 +/- 18.6 vs. 138.5 +/- 24.6
      mm Hg, p = 0.0309) were all significantly lower in patients who achieved good
      outcomes. A lower maximum intraprocedural SBP was an independent predictor of
      good outcome (adjusted OR 0.929, 95% CI 0.886-0.963, p = 0.0005). Initial NIHSS
      score was the only other independent predictor of a good outcome. CONCLUSION:
      Lower intraprocedural SBP was associated with good outcome in patients undergoing
      IAT for AIS, and maximum SBP was an independent predictor of good outcome. SBP
      may be the optimal hemodynamic variable to monitor intraprocedurally during IAT
      and may predict outcome.

PMID- 27051412
TI  - Contrast-Based 3D/2D Registration of the Left Atrium: Fast versus Consistent.
AB  - For augmented fluoroscopy during cardiac ablation, a preoperatively acquired 3D
      model of a patient's left atrium (LA) can be registered to X-ray images recorded
      during a contrast agent (CA) injection. An automatic registration method that
      works also for small amounts of CA is desired. We propose two similarity
      measures: The first focuses on edges of the patient anatomy. The second computes
      a contrast agent distribution estimate (CADE) inside the 3D model and rates its
      consistency with the CA as seen in biplane fluoroscopic images. Moreover,
      temporal filtering on the obtained registration results of a sequence is applied
      using a Markov chain framework. Evaluation was performed on 11 well-contrasted
      clinical angiographic sequences and 10 additional sequences with less CA. For
      well-contrasted sequences, the error for all 73 frames was 7.9 +/- 6.3 mm and it
      dropped to 4.6 +/- 4.0 mm when registering to an automatically selected, well
      enhanced frame in each sequence. Temporal filtering reduced the error for all
      frames from 7.9 +/- 6.3 mm to 5.7 +/- 4.6 mm. The error was typically higher if
      less CA was used. A combination of both similarity measures outperforms a
      previously proposed similarity measure. The mean accuracy for well contrasted
      sequences is in the range of other proposed manual registration methods. 

PMID- 27051413
TI  - Possible Role of Interaction between PPARalpha and Cyclophilin D in
      Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats.
AB  - Activated AMPK protects the heart from cardiac ischemia-reperfusion (IR) injury
      and is associated with inhibition of mitochondrial permeability transition pore
      (PTP) opening. On the other hand, pharmacological inhibition of the PTP reduces
      infarct size and improves cardiac function. However, it is unclear whether
      beneficial effects of AMPK are mediated through the PTP and, if they are not,
      whether simultaneous activation of AMPK and inhibition of the PTP exert
      synergistic protective effects against cardiac IR injury. Here, we examined the
      effects of the AMPK activator, A-769662 in combination with the PTP inhibitor,
      sanglifehrin A (SfA) on in vivo cardiac IR. Cardiac dysfunction following IR
      injury was associated with decreased activity of the mitochondrial electron
      transport chain (ETC) and increased mitochondrial ROS and PTP opening.
      Administration of A-769662 or SfA individually upon reperfusion improved cardiac
      function, reduced infarction size, and inhibited ROS production and PTP opening.
      However, simultaneous administration of SfA and A-769662 did not provide
      synergistic improvement of postischemic recovery of cardiac and mitochondrial
      function, though both compounds disrupted IR-induced interaction between
      PPARalpha and CyP-D. In conclusion, A-769662 or SfA prevents PPARalpha
      interaction with CyP-D, improving cardiac outcomes and increasing mitochondrial
      function, and simultaneous administration of the drugs does not provide
      synergistic effects. 

PMID- 27051414
TI  - A Prototype SSVEP Based Real Time BCI Gaming System.
AB  - Although brain-computer interface technology is mainly designed with disabled
      people in mind, it can also be beneficial to healthy subjects, for example, in
      gaming or virtual reality systems. In this paper we discuss the typical
      architecture, paradigms, requirements, and limitations of electroencephalogram
      based gaming systems. We have developed a prototype three-class brain-computer
      interface system, based on the steady state visually evoked potentials paradigm
      and the Emotiv EPOC headset. An online target shooting game, implemented in the
      OpenViBE environment, has been used for user feedback. The system utilizes wave
      atom transform for feature extraction, achieving an average accuracy of 78.2%
      using linear discriminant analysis classifier, 79.3% using support vector machine
      classifier with a linear kernel, and 80.5% using a support vector machine
      classifier with a radial basis function kernel. 

PMID- 27051415
TI  - Production of a Self-Aligned Scaffold, Free of Exogenous Material, from Dermal
      Fibroblasts Using the Self-Assembly Technique.
AB  - Many pathologies of skin, especially ageing and cancer, involve modifications in
      the matrix alignment. Such tissue reorganization could have impact on cell
      behaviour and/or more global biological processes. Tissue engineering provides
      accurate study model by mimicking the skin and it allows the construction of
      versatile tridimensional models using human cells. It also avoids the use of
      animals, which gave sometimes nontranslatable results. Among the various
      techniques existing, the self-assembly method allows production of a near native
      skin, free of exogenous material. After cultivating human dermal fibroblasts in
      the presence of ascorbate during two weeks, a reseeding of these cells takes
      place after elevation of the resulting stroma on a permeable ring and culture
      pursued for another two weeks. This protocol induces a clear realignment of
      matrix fibres and cells parallel to the horizon. The thickness of this stretched
      reconstructed tissue is reduced compared to the stroma produced by the standard
      technique. Cell count is also reduced. In conclusion, a new, easy, and
      inexpensive method to produce aligned tissue free of exogenous material could be
      used for fundamental research applications in dermatology. 

PMID- 27051416
TI  - Cytokines as Early Markers of Colorectal Anastomotic Leakage: A Systematic Review
      and Meta-Analysis.
AB  - Purpose. Colorectal anastomotic leakage (CAL) is one of the most severe
      complications after colorectal surgery. This meta-analysis evaluates whether
      systemic or peritoneal inflammatory cytokines may contribute to early detection
      of CAL. Methods. Systematic literature search was performed in the acknowledged
      medical databases according to the PRISMA guidelines to identify studies
      evaluating systemic and peritoneal levels of TNF, IL-1beta, IL-6, and IL-10 for
      early detection of CAL. Means and standard deviations of systemic and peritoneal
      cytokine levels were extracted, respectively, for patients with and without CAL.
      The meta-analysis of the mean differences was carried out for each postoperative
      day using Review Manager. Results. Seven articles were included. The meta
      analysis was performed with 5 articles evaluating peritoneal cytokine levels.
      Peritoneal levels of IL-6 were significantly higher in patients with CAL compared
      to patients without CAL on postoperative days 1, 2, and 3 (P < 0.05). Similar
      results were found for peritoneal levels of TNF but on postoperative days 3, 4,
      and 5 (P < 0.05). The articles regarding systemic cytokine levels did not report
      any significant difference accordingly. Conclusion. Increased postoperative
      levels of peritoneal IL-6 and TNF are significantly associated with CAL and may
      contribute to its early detection. 

PMID- 27051418
TI  - Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by
      Different Routes to Llamas (Lama glama).
AB  - We investigate the pharmacokinetics of two different cephalexin formulations
      administered to llamas by the intravenous (IV), intramuscular (IM), and
      subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of
      cephalexin against some Escherichia coli and staphylococci isolated from llamas,
      and we apply the PK/PD modelling approach, so that effective dosage
      recommendations for this species could be made. Six llamas received immediate (10
      mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin.
      Pharmacokinetic parameters were calculated by noncompartmental approach.
      Immediate release SC administration produced a significantly longer elimination
      half-life as compared with the IV and IM administration (1.3 +/- 0.2 versus 0.6
      +/- 0.1 and 0.6 +/- 0.1 h, resp.) and higher mean absorption time as compared
      with the IM administration (1.7 +/- 0.5 versus 0.6 +/- 0.4 h). Absolute
      bioavailability was in the range of 72-89% for both formulations and routes of
      administration. Cephalexin MIC90 values against staphylococci and E. coli were
      1.0 and 8.0 MUg/mL, respectively. Our results show that the immediate release
      formulation (10 mg/kg) would be effective for treating staphylococcal infections
      administered every 8 h (IM) or 12 h (SC), whereas the sustained release
      formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h,
      respectively. 

PMID- 27051417
TI  - Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional
      Approaches Effect a Systemic Response?
AB  - Percutaneous image-guided ablation is an increasingly common treatment for a
      multitude of solid organ malignancies. While historically these techniques have
      been restricted to the management of small, unresectable tumors, there is an
      expanding appreciation for the systemic effects these locoregional interventions
      can cause. In this review, we summarize the mechanisms of action for the most
      common thermal ablation modalities and highlight the key advances in knowledge
      regarding the interactions between thermal ablation and the immune system. 

PMID- 27051419
TI  - Urethral Stricture Disease: Challenges and Ongoing Controversies.

PMID- 27051420
TI  - Sexual (Dys)function after Urethroplasty.
AB  - There is a paucity of published literature on the andrological consequences of
      urethral repair. Until recently authors have focused mainly on technical aspects
      and objective results. Reported outcomes of urethral reconstruction surgery have
      traditionally focused only on urodynamic parameters such as flow rates. Patient
      reported outcome measures have largely been neglected and there is a scarcity of
      well conducted systematic studies on the subject. For these reasons whether the
      different components of sexual life are more or less affected by different types
      of urethral reconstruction remains largely unknown. In an attempt to clarify the
      available scientific evidence, the authors make a critical review of available
      literature, systematizing it by sexual domain and study type. Brief
      pathophysiological correlations are discussed. 

PMID- 27051421
TI  - Dexmedetomidine versus Magnesium Sulfate as Adjunct during Anesthesia for
      Laparoscopic Colectomy.
AB  - Objectives. To compare dexmedetomidine versus magnesium during laparoscopic
      colectomy. Patients and Methods. 51 patients were randomly allocated into 3
      groups: group C (control) received saline infusion, group D dexmedetomidine 1
      g/kg and then 0.4 g/kg/hr, and group M MgSO4 2 g and then 15 g/kg/min.
      Intraoperative hemodynamics were measured before and 1 min after intubation (T1
      and T2), before and 5 min after peritoneal insufflation (T3 and T4), before and 5
      min after 30 degrees  Trendelenburg position (T5 and T6), 5 min after resuming
      flat position (T7), 5 min after peritoneal deflations (T8), after extubation
      (T9), and at time of admission to PACU (T10). Recovery time and degree of
      sedation were assessed. Results. HR and MAP were significantly higher in T2, T4,
      and T6 compared to T1, T3, and T5, respectively, in all groups with lower
      measurements in groups D and M compared to group C. Mean of collective
      measurements was significantly higher in group C. Recovery time and sedation
      score were significantly higher in groups D and M. Time to Aldrete score of >=9
      was significantly longer in groups D and M. Conclusion. Both drugs ameliorate the
      pressor responses during LC with a nonsignificant difference. This study is
      registered with PACTR201602001481308. 

PMID- 27051422
TI  - Parasitaemia and Its Relation to Hematological Parameters and Liver Function
      among Patients Malaria in Abs, Hajjah, Northwest Yemen.
AB  - Plasmodium falciparum malaria is the most common infection in Yemen. The present
      study aims to investigate changes in hematological and hepatic function indices
      of P. falciparum infected individuals. This study included 67 suspected
      falciparum malarial patients attended in clinics and rural Abs Hospital (Tehama,
      Hajjah), Yemen, from October 2013 to April 2014. The diagnosis of malaria was
      confirmed by thick and thin film with Giemsa staining of malaria parasite.
      Hematological parameters and serum levels of aspartate transaminase (AST),
      alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin (total and
      direct) as test indicators of liver function were studied. Patients with
      parasitaemia tended to have significantly lower hemoglobin, hematocrit, white
      blood cell count, lymphocytes, and platelets, compared with healthy normal
      subjects. Neutrophils levels were significantly higher in cases of falciparum
      malaria in comparison to healthy normal subjects. Serums AST, ALT, ALP, and
      bilirubin (total and direct) in falciparum malaria patients were significantly
      higher (p < 0.0001) than those of falciparum malaria of free individuals.
      Hematological and liver dysfunctions measured parameters were seen associated
      with moderate and severe parasitaemia infection. This study concludes that
      hematological and hepatic dysfunction parameters could be indicator of malaria in
      endemic regions. 

PMID- 27051424
TI  - BK Virus Load Associated with Serum Levels of sCD30 in Renal Transplant
      Recipients.
AB  - Background. Rejection is the main drawback facing the renal transplant
      operations. Complicated and overlapping factors, mainly related to the immune
      system, are responsible for this rejection. Elevated serum levels of sCD30 were
      frequently recorded as an indicator for renal allograft rejection, while BV virus
      is considered as one of the most serious consequences for immunosuppressive
      treatment of renal transplant recipients (RTRs). Aims. This study aimed to
      determine the association of BK virus load with serum levels of sCD30 in RTRs
      suffering from nephropathy. Patients and Methods. A total of 50 RTRs with
      nephropathy and 30 age-matched apparently healthy individuals were recruited for
      this study. Serum samples were obtained from each participant. Real-time PCR was
      used to quantify BK virus load in RTRs serum, while ELISA technique was employed
      to estimate serum levels of sCD30. Results. Twenty-two percent of RTRs had
      detectable BKV with mean viral load of 1.094E + 06 +/- 2.291E + 06. RTRs showed
      higher mean serum level of sCD30 (20.669 +/- 18.713 U/mL) than that of controls
      (5.517 +/- 5.304 U/mL) with significant difference. BK virus load had significant
      positive correlation with the serum levels of sCD30 in RTRs group. Conclusion.
      These results suggest that serum levels of sCD30 could be used as an indicator of
      BK viremia, and accordingly the immunosuppressive regime should be adjusted. 

PMID- 27051423
TI  - Bacteria in Cancer Therapy: Renaissance of an Old Concept.
AB  - The rising incidence of cancer cases worldwide generates an urgent need of novel
      treatment options. Applying bacteria may represent a valuable therapeutic variant
      that is intensively investigated nowadays. Interestingly, the idea to apply
      bacteria wittingly or unwittingly dates back to ancient times and was revived in
      the 19th century mainly by the pioneer William Coley. This review summarizes and
      compares the results of the past 150 years in bacteria mediated tumor therapy
      from preclinical to clinical studies. Lessons we have learned from the past
      provide a solid foundation on which to base future efforts. In this regard,
      several perspectives are discussed by which bacteria in addition to their
      intrinsic antitumor effect can be used as vector systems that shuttle therapeutic
      compounds into the tumor. Strategic solutions like these provide a sound and more
      apt exploitation of bacteria that may overcome limitations of conventional
      therapies. 

PMID- 27051425
TI  - Absence of Flexor Carpi Radialis during an Elective Carpometacarpal Arthroplasty
      of the Thumb: A Rare Anatomical Variation.
AB  - Purpose. We present an extremely rare anatomical variation of unilateral flexor
      carpi radialis (FCR) absence. This rare anatomical variation posed a clinical
      dilemma to us and we highlight the importance of the surgeon being aware of this
      anatomical variation of an important structure both as a reconstruction tool and
      as an anatomical landmark. Methods. This anatomical variation of the unilaterally
      absent FCR was found upon dissection during a carpometacarpal arthroplasty of the
      thumb. Results. Upon the discovery of an absent FCR tendon, we proceeded with a
      simple trapeziectomy. Conclusions. We present an extremely rare anatomical
      variation of unilateral FCR absence. This rare anatomical variation may pose
      clinical dilemmas to the operating surgeon who aims to utilise the FCR either for
      tendon transfer, for tendon graft, or, as seen in our case, in the reconstruction
      of a carpometacarpal excision at the thumb. We highlight this diagnosis of
      suspicion, which may influence the clinical procedure. 

PMID- 27051426
TI  - The Therapeutic Effect of Adipose-Derived Mesenchymal Stem Cells for Radiation
      Induced Bladder Injury.
AB  - This study was designed to investigate the protective effect of adipose derived
      mesenchymal stem cells (AdMSCs) against radiation-induced bladder injury (RIBI).
      Female rats were divided into 4 groups: (a) controls, consisting of nontreated
      rats; (b) radiation-treated rats; (c) radiation-treated rats receiving AdMSCs;
      and (d) radiation-treated rats receiving AdMSCs conditioned medium. AdMSCs or
      AdMSCs conditioned medium was injected into the muscular layer of bladder 24 h
      after radiation. Twelve weeks after radiation, urinary bladder tissue was
      collected for histological assessment and enzyme-linked immunosorbent assay
      (ELISA) after metabolic cage investigation. At the 1 w, 4 w, and 8 w time points
      following cells injection, 3 randomly selected rats in RC group and AdMSCs group
      were sacrificed to track injected AdMSCs. Metabolic cage investigation revealed
      that AdMSCs showed protective effect for radiation-induced bladder dysfunction.
      The histological and ELISA results indicated that the fibrosis and inflammation
      within the bladder were ameliorated by AdMSCs. AdMSCs conditioned medium showed
      similar effects in preventing radiation-induced bladder dysfunction. In addition,
      histological data indicated a time-dependent decrease in the number of AdMSCs in
      the bladder following injection. AdMSCs prevented radiation induced bladder
      dysfunction and histological changes. Paracrine effect might be involved in the
      protective effects of AdMSCs for RIBI. 

PMID- 27051427
TI  - Quinazolinone and quinazoline derivatives: recent structures with potent
      antimicrobial and cytotoxic activities.
AB  - The heterocyclic compounds have a great importance in medicinal chemistry. One of
      the most important heterocycles in medicinal chemistry are quinazolines
      possessing wide spectrum of biological properties like antibacterial, antifungal,
      anticonvulsant, anti-inflammatory, anti-HIV, anticancer and analgesic activities.
      This skeleton is an important pharmacophore considered as a privileged structure.
      This review highlights the recent advances in the synthesis of quinazolines and
      quinazolinone derivatives with potent antimicrobial and cytotoxic activities. 

PMID- 27051428
TI  - Antinociceptive effect of aqueous extracts from the bark of Croton guatemalensis
      Lotsy in mice.
AB  - Croton guatemalensis Lotsy (CGL), known as "copalchi" in Chiapas, Mexico, is used
      for the treatment of fever, abdominal pain and malaria and also as a remedy for
      chills and for treating rheumatism. The aim of this study was to evaluate whether
      aqueous extracts from the bark of this plant possesses indeed antinociceptive
      properties by using two different animal models of nociception, the acetic acid
      induced writhing test and the hot plate model. The results showed that i.p.
      administration of this extract (0, 100, 200 and 400 mg/kg) 30 min prior testing
      had significant dose-dependent antinociceptive effects in the acetic acid-induced
      writhing test and that the reduction of writhings (85.5 % as compared to the
      control) at the highest dose tested is similar to that exhibited by dipyrone (250
      mg/kg). This effect was not reversed by naloxone, a non-selective opioid receptor
      antagonist, suggesting that the endogenous opioid system does not underlie the
      antinociceptive effects of CGL in the acetic acid-induced writhing test. No
      effects were however observed in the hot-plate model. Our results indicate that
      aqueous extracts from Croton guatemalensis bark contain pharmacologically active
      constituents endowed with antinociceptive activity. It is suggested that
      cyclooxygenase inhibition might be at least partially involved in the
      antinociceptive effects of this extract. 

PMID- 27051429
TI  - Chemical constituents of Swertia longifolia Boiss. with alpha-amylase inhibitory
      activity.
AB  - alpha-Amylase inhibitors play a critical role in the control of diabetes and many
      of medicinal plants have been found to act as alpha-amylase inhibitors. Swertia
      genus, belonging to the family Gentianaceae, comprises different species most of
      which have been used in traditional medicine of several cultures as antidiabetic,
      anti-pyretic, analgesic, liver and gastrointestinal tonic. Swertia longifolia
      Boiss. is the only species of Swertia growing in Iran. In the present
      investigation, phytochemical study of S. longifolia was performed and alpha
      amylase inhibitory effects of the plant fractions and purified compounds were
      determined. Aerial parts of the plant were extracted with hexane, chloroform,
      methanol and water, respectively. The components of the hexane and chloroform
      fractions were isolated by different chromatographic methods and their structures
      were determined by (1)H NMR and (13)C NMR data. alpha-Amylase inhibitory activity
      was determined by a colorimetric assay using 3,5-dinitro salysilic acid. During
      phytochemical examination, alpha-amyrin, beta-amyrin and beta-sitosterol were
      purified from the hexane fraction, while ursolic acid, daucosterol and
      swertiamarin were isolated from chloroform fraction. The results of the
      biochemical assay revealed alpha-amylase inhibitory activity of hexane,
      chloroform, methanol and water fractions, of which the chloroform and methanol
      fractions were more potent (IC50 16.8 and 18.1 mg/ml, respectively). Among
      examined compounds, daucosterol was found to be the most potent alpha-amylase
      inhibitor (57.5% in concentration 10 mg/ml). With regard to alpha-amylase
      inhibitory effects of the plant extracts, purified constituents, and antidiabetic
      application of the species of Swertia genus in traditional medicine of different
      countries, S. longifolia seems more appropriate species for further mechanistic
      antidiabetic evaluations. 

PMID- 27051430
TI  - Anti-spasmodic assessment of hydroalcoholic extract and essential oil of aerial
      part of Pycnocycla caespitosa Boiss. & Hausskn on rat ileum contractions.
AB  - Pycnocycla caespitosa is an essential oil-containing plant naturally growing in
      southwest of Iran. The extract of this plant has been used as remedy in
      traditional medicine. Another species of Pycnocyla (P. spinosa) possessed
      antispasmodic activity. The pharmacological objective of this study was to look
      for relaxant effect of hydroalcoholic extract and essential oil of P. caespitosa
      on rat isolated ileum contractions for comparison with loperamide. The essential
      oil and the hydroalcoholic extract were prepared by hydrodistillation and
      percolation techniques, respectively. For antispasmodic studies a section of rat
      ileum was suspended in an organ bath containing Tyrode's solution. The tissue was
      stimulated with electrical field stimulation (EFS), KCl (80 mM) and acetylcholine
      (ACh 0.5 MUM). The tissue was kept under 1 g tension at 37 degrees C and
      continuously gassed with O2. The essential oil content in the aerial parts of P.
      caespitosa was found to be 0.16 % ml/g. The essential oil was analyzed by gas
      chromatography and gas chromatography-mass spectrometry. Seventy constituents,
      representing 97 % of the oil were identified. The major components of the oil
      were carvacrol (7.1%), beta-eudesmol (6.4 %), rho-cymene (5.7%), caryophyllene
      oxide (3.6%), alpha-pinine (1.4%) and alpha-phelandrene (1.1%). The
      hydroalcoholic extract of P. caespitosa inhibited the response to KCl (IC50 = 48
      +/- 3 MUg/ml), ACh (IC50 = 61 +/- 14.7 MUg/ml) and EFS (IC50 = 77 +/- 17 MUg/ml)
      in a concentration-dependent manner. The essential oil of P. caespitosa also
      inhibited rat ileum contractions. The IC50 values for KCl, ACh and EFS were 9.2
      +/- 1.2 MUg/ml, 7.6 +/- 0.8 MUg/ml and 6.4 +/- 0.8 MUg/ml, respectively. The
      inhibitory effect of both the essential oil and the extract were reversible. This
      research confirms the anti-spasmodic activity of both the essential oil and the
      extract of P. caespitosa on smooth muscle contraction of ileum. 

PMID- 27051431
TI  - Production of human epidermal growth factor using adenoviral based system.
AB  - Epidermal growth factor (EGF), a growth factor involved in cell growth and
      differentiation, is a small polypeptide with molecular weight of approximately 6
      kDa known to be present in a number of different mammalian species. Experimental
      studies in animals and humans have demonstrated that the topical application of
      EGF accelerates the rate of epidermal regeneration of partial-thickness wounds
      and second-degree burns. Due to its commercial applications, Human EGF (hEGF) has
      been cloned in several forms. In the present study, adenoviral based expression
      system was used to produce biologically active recombinant hEGF. The presence of
      secreted recombinant hEGF was confirmed by a dot blot and its expression level
      was determined by enzyme-linked immuno-sorbent assay. Moreover, biological
      activity of secreted hEGF was evaluated by a proliferation assay performed on
      A549 cells. For production of hEGF in a secretory form, a chimeric gene coding
      for the hEGF fused to the signal peptide was expressed using adenoviral based
      method. This method enables the production of hEGF at the site of interest and
      moreover it could be used for cell proliferation and differentiation assays in
      tissue engineering research experiments instead of using commercially available
      EGF. 

PMID- 27051433
TI  - Anti-pseudomonas activity of essential oil, total extract, and proanthocyanidins
      of Pinus eldarica Medw. bark.
AB  - Pinus eldarica Medw. (Iranian pine) is native to Transcaucasian region and has
      been vastly planted in Iran, Afghanistan, and Pakistan. Various parts of this
      plant have been widely used in traditional medicine for the treatment of various
      diseases including infectious conditions (e.g. infectious wounds). In this study
      we aimed to investigate the antibacterial activity of P. eldarica bark extract,
      essential oil and proanthocyanidins on three important bacteria, Staphylococcus
      aureus, Escherichia coli and Pseudomonas aeruginosa. Antibacterial analysis was
      performed using standard disk diffusion method with different concentrations of
      essential oil, bark total hydroalcoholic extract, and bark proanthocyanidins
      (0.5, 1, 2 and 3 mg/ml). After incubation at 37 degrees C for 24 h, the
      antibacterial activity was assessed by measuring the zone of growth inhibition
      surrounding the disks. The results indicated that the essential oil, total
      hydroalcoholic extract, and proanthocyanidins of the bark of the P. eldarica were
      effective against the gram negative bacteria, P. aeruginosa, and significantly
      inhibited its growth in disk diffusion method (P<0.001) of which the essential
      oil had the most potent inhibitory effect. However, none of the bark preparations
      could significantly inhibit the growth of S. aureus or E. coli. Our findings
      showed that P. eldarica bark components have significant anti-pseudomonas
      activity having potentials for new sources of antibacterial agents or
      antibacterial herbal preparations. 

PMID- 27051432
TI  - Acute and chronic tramadol administration impair spatial memory in rat.
AB  - Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of
      action. Tramadol can potentially change the behavioral phenomena. The present
      study evaluates the effect of tramadol after single or multiple dose/s on the
      spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg,
      was injected intraperitoneally (i.p) as a single dose or once a day for 21
      successive days considered as acute or chronic treatment respectively. After
      treatment, animals underwent two trials in the ORT. In the first trial (T1),
      animals encountered with two identical objects for exploration in a five-minute
      period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a
      nonfamiliar object. The exploration times and frequency of the exploration for
      any objects were recorded. The results showed that tramadol decreased the
      exploration times for the nonfamiliar object in the T2 trial when administered
      either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to
      the respective control groups. Both acute and chronic tramadol administration
      eliminated the different frequency of exploration between the familiar and
      nonfamiliar objects. Our findings revealed that tramadol impaired memory when
      administered acutely or chronically. Single dose administration of tramadol
      showed more destructive effect than multiple doses of tramadol on the memory. The
      observed data can be explained by the inhibitory effects of tramadol on the wide
      range of neurotransmitters and receptors including muscarinic, N-methyl D
      aspartate, AMPA as well as some second messenger like cAMP and cGMP or its
      stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin
      in the brain. 

PMID- 27051434
TI  - Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in
      ovariectomized estradiol treated rats.
AB  - The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes
      the function of angiotensin II through Mas receptor (MasR) or other unknown
      mechanisms. In the current study, the role of MasR and steroid hormone estrogen
      on renal blood flow response to Ang 1-7 administration was investigated in
      ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500
      MUg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals
      were anesthetized, cannulated, and the responses including mean arterial
      pressure, renal blood flow (RBF), and renal vascular resistance at the constant
      level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300
      ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with
      vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose
      dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals.
      However, when MasR was blocked, the RBF response to Ang 1-7 significantly
      increased in OV animals compared with OVE rats (P<0.05). When estradiol was
      limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration,
      while this response was attenuated in OVE animals. 

PMID- 27051435
TI  - Cytotoxic evaluation of different fractions of Salvia chorassanica Bunge on MCF-7
      and DU 145 cell lines.
AB  - Because of antimicrobial, antioxidant, and anticancer potential, Salvia
      chorassanica Bunge (Lamiaceae) has been considered as a popular herb in Iranian
      traditional medicine. Previous studies have shown remarkable cytotoxic properties
      of the methanol, n-hexane and dichloromethane extract of S. chorassanica on human
      cervical cancer cells. To seek the therapeutic potentials of S. chorassanica,
      this study was undertaken to evaluate the cytotoxic activities of various
      extracts of this plant on human breast MCF-7 and prostate cancer DU 145 cells.
      The DU 145 cells were exposed to different concentrations of plant extracts (1
      200 MUg/ml). Cytotoxic activities were examined using alamarBlue((r)) assay and
      apoptosis was assessed by acridine orange/propodium iodide double staining and
      evaluation of DNA fragmentation by flow cytometry. Our findings indicated that n
      hexane and dichloromethane extracts had more cytotoxic activities against DU 145
      and MCF-7 cell lines compared with other extracts (P<0.05). The acridine
      orange/propodium iodide staining showed apoptogenic properties of n-hexane and
      dichloromethane extracts which was consequently confirmed by flow cytometric
      histogram that exhibited an increase in sub-G1 peak in treated cells as compared
      with untreated cancer cell lines. Taken together, these observations demonstrated
      cytotoxic effects of S. chorassanica extracts on MCF-7 and DU 145 cell lines
      which is most likely exerted via apoptosis cell death. Therefore, further
      investigations on S. chorassanica extracts as potential chemotherapeutic agents
      are warranted. 

PMID- 27051436
TI  - Design and in vitro evaluation of a novel controlled onset extended-release
      delivery system of metoprolol tartrate.
AB  - Blood pressure rises rapidly upon awakening and maybe responsible, in part, for
      the increased incidence of myocardial infarction and stroke during the morning
      hours. The aim of the present study was, therefore, to develop a novel
      chronotherapeutic formulation of metoprolol tartrate (MT) for night time dosing
      providing maximum effect in the morning hours. Core tablets contained MT, sodium
      chloride, lactose, Avicel((r)) and starch. Powders were mixed, sieved and
      directly compressed in to tablets using a single punch tablet machine. Core
      tablets were then coated with 5 or 10% hydroxypropyl methylcellulose as swelling
      layer and subsequently outer membrane with the mixture of various ratios of
      Eudragit((r)) RS to RL at different coating levels 5, 10, 15% as semi-permeable
      water insoluble outer coat by conventional pan-spray method. The best formulation
      with regard to release behavior was chosen and subjected to further release
      studies in various rotational speed and pHs. Both lag time and release rate were
      dependent on the coating levels and the osmotic pressure of dissolution medium. A
      linear relationship between lag time and outer coating levels was observed. The
      lag time was prolonged with an increase in the coating levels. Both diffusion and
      osmotic pumping effect were involved in drug release from the device. Significant
      increases in drug release behavior was not observed using dissolution medium with
      various pH and different agitation rates. It was found that the release rate was
      independent of pH, rotational speed and gastric motility and may not be altered
      due to changes of pH and peristaltic movement along the GI tract. 

PMID- 27051437
TI  - Postnatal changes in glucose transporter 3 expression in the dentate gyrus of the
      C57BL/6 mouse model.
AB  - In this study, we observed the ontogenetic changes in glucose transporter 3
      (GLUT3) immunoreactivity, a major neuronal GLUT, in the dentate gyrus of mouse
      brains at various ages: postnatal day (P) 1, 7, 14, 28, and 56. At P1, cresyl
      violet staining showed abundant neurons in the dentate gyrus, whereas the granule
      cell layer was ill-defined. At P7, the granule cell layer was observed, and
      cresyl violet-positive cells were dispersed throughout the polymorphic layer. At
      P14, the granule cell layer was well-defined, and cresyl violet positive cells
      were detected abundantly in the polymorphic layer. At P28 and P56, cresyl violet
      positive cells were observed in the granule cell layer, as well as in the
      polymorphic layer. At P1, GLUT3 immunoreactivity was detected in the dentate
      gyrus. At P7, GLUT3 immunoreactive cells were scattered in the polymorphic and
      molecular layer. However, at P14, GLUT3 immunoreactivity was observed in the
      polymorphic layer as well as subgranular zone of the dentate gyrus. At P28, GLUT3
      immunoreactivity was detected in the polymorphic layer of the dentate gyrus. At
      P56, GLUT3 immunoreactivity was observed predominantly in the subgranular zone of
      the dentate gyrus. GLUT3 immunoreactive cells were mainly colocalized with
      doublecortin, which is a marker for differentiated neuroblasts, in the
      polymorphic layer and subgranular zone of dentate gyrus at P14 and P56. These
      results suggest that the expression of GLUT3 is closely associated with postnatal
      development of the dentate gyrus and adult neurogenesis. 

PMID- 27051438
TI  - Cardiopulmonary effects of thiopental versus propofol as an induction agent prior
      to isoflurane anesthesia in chair trained rhesus macaques (Macaca mulatta).
AB  - The purpose of this study was to evaluate the effects of thiopental versus
      propofol on cardiopulmonary functions, when used as an induction agent prior to
      isoflurane anesthesia in rhesus monkeys. Eight healthy rhesus monkeys weighing
      3.72 to 5.7 kg, 4-5 years old, were used in the study. Anesthesia was induced
      with thiopental or propofol intravenous injection, and then maintained with
      isoflurane in oxygen for 45 minutes. Cardiopulmonary measurements were obtained
      before and 5, 15, 30, 45, and 60 minutes after induction. The induction doses of
      thiopental and propofol were 19.41+/-0.54 and 9.33+/-1.02 mg/kg, respectively. In
      both groups, the values of heart rate, respiratory rate, temperature, systolic
      blood pressure, mean blood pressure, diastolic blood pressure, pH, and lactate
      were decreased, while the values of partial pressure of carbon dioxide, partial
      pressure of oxygen, total carbon dioxide, bicarbonate, oxygen saturation, and
      base excess in the extracellular fluid were increased, as compared with baseline.
      Systolic blood pressure was significantly lower in thiopental group compare to
      propofol group. Induction time was very short in both agents but not revealed a
      significant difference between both groups. However, recovery time was extremely
      faster in the propofol group. Our results demonstrated that propofol provides a
      minor suppression in systolic arterial blood pressure than thiopental sodium. In
      addition, propofol have a fast recovery effect from the anesthesia as well.
      Furthermore, it is suggested that thiopental sodium could also be used to induce
      anesthesia instead of propofol, despite slight more suppression of
      cardiopulmonary function compared to thiopental sodium. 

PMID- 27051439
TI  - Laxative effects of Liriope platyphylla are tightly correlated with suppression
      of endoplasmic reticulum stress in loperamide-induced constipation of SD rats.
AB  - A dysfunction of endoplasmic reticulum (ER) stress response can result in various
      diseases, including cancer, inflammation, diabetes and neurodegenerative
      disorders. To investigate whether ER stress response can play an essential role
      in the induction and treatment of chronic constipation, alterations in the key
      parameters for ER stress were measured in loperamide (Lop) induced constipation
      Sprague Dawley (SD) rats treated with aqueous extracts of Liriope platyphylla
      (AEtLP), which has been shown to have a laxative effect. Symptoms of chronic
      constipation including alteration of stool parameters and the transverse colon's
      structure were successfully induced by Lop treatment. Laxative effects such as
      enhancement of stools parameters, recovery of the mucosa thickness, increased
      muscle thickness and recovery of flat luminal surface were also observed in the
      Lop+AEtLP treated group. Furthermore, enhancement of eukaryotic initiation factor
      2 alpha (eIF2alpha) phosphorylation and inositol-requiring enzyme 1 beta
      (IRE1beta) expression, key indicators for ER stress, that were observed in the
      Lop+vehicle treated group were significantly recovered in the Lop+AEtLP treated
      group, although the phosphorylation level of c-Jun N-terminal protein kinase
      (JNK) remained constant. Moreover, alterations in the transcription level of the
      marker genes X-box binding protein 1 (XBP-1) and growth arrest and DNA damage
      inducible protein (GADD34) were similar to those of eIF2alpha and IRE1beta.
      However, their level was slightly or completely recovered after AEtLP treatment.
      Overall, this study provides the first evidence that ER stress response may be
      tightly correlated with chronic constipation induced by Lop treatment, as well as
      the laxative effects of AEtLP. 

PMID- 27051440
TI  - Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3
      dichloro-2-propanol-induced hepatic injury.
AB  - In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its
      hepatotoxic mechanisms in rats was investigated. The test chemical was
      administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3
      Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by
      an increase in serum aminotransferases, total cholesterol, and total bilirubin
      levels and a decrease in serum glucose concentration in a dose-dependent manner
      with corresponding histopathological changes in the hepatic tissues. The
      significant increase in malondialdehyde content and the significant decrease in
      glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro
      2-propanol-induced hepatic damage was mediated through oxidative stress, which
      caused a dose-dependent increase of hepatocellular apoptotic changes in the
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and
      immunohistochemical analysis for caspase-3. The phosphorylation of mitogen
      activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in
      hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2
      propanol induced an inflammatory response through activation of nuclear factor
      kappa B signaling that coincided with the induction of pro-inflammatory mediators
      or cytokines in a dose-dependent manner. Taken together, these results
      demonstrate that hepatotoxicity may be related to oxidative stress-mediated
      activation of mitogen-activated protein kinases and nuclear factor-kappa B
      mediated inflammatory response. 

PMID- 27051441
TI  - Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on
      phthalic anhydride-induced skin inflammation.
AB  - Asparagus cochinchinensis has been used to treat various diseases including
      fever, cough, kidney disease, breast cancer, inflammatory disease and brain
      disease, while IL-4 cytokine has been considered as key regulator on the skin
      homeostasis and the predisposition toward allergic skin inflammation. However,
      few studies have investigated its effects and IL-4 correlation on skin
      inflammation to date. To quantitatively evaluate the suppressive effects of ethyl
      acetate extracts of A. cochinchinensis (EaEAC) on phthalic anhydride (PA)-induced
      skin inflammation and investigate the role of IL-4 during their action mechanism,
      alterations in general phenotype biomarkers and luciferase-derived signals were
      measured in IL-4/Luc/CNS-1 transgenic (Tg) mice with PA-induced skin inflammation
      after treatment with EaEAC for 2 weeks. Key phenotype markers including lymph
      node weight, immunoglobulin E (IgE) concentration, epidermis thickness and number
      of infiltrated mast cells were significantly decreased in the PA+EaEAC treated
      group compared with the PA+Vehicle treated group. In addition, expression of IL
      1beta and TNF-alpha was also decreased in the PA+EaEAC cotreated group, compared
      to PA+Vehicle treated group. Furthermore, a significant decrease in the
      luciferase signal derived from IL-4 promoter was detected in the abdominal
      region, submandibular lymph node and mesenteric lymph node of the PA+EaEAC
      treated group, compared to PA+Vehicle treated group. Taken together, these
      results suggest that EaEAC treatment could successfully improve PA-induced skin
      inflammation of IL-4/Luc/CNS-1 Tg mice, and that IL-4 cytokine plays a key role
      in the therapeutic process of EaEAC. 

PMID- 27051442
TI  - Reference values of hematology, biochemistry, and blood type in cynomolgus
      monkeys from cambodia origin.
AB  - Cynomolgus monkeys as nonhuman primates are valuable animal models because they
      have a high level of human gene homology. There are many reference values for
      hematology and biochemistry of Cynomolgus monkeys that are needed for proper
      clinical diagnosis and biomedical research conduct. The body weight information
      and blood type are also key success factors in allogeneic or xenogeneic models.
      Moreover, the biological parameters could be different according to the origin of
      the Cynomolgus monkey. However, there are limited references provided, especially
      of Cambodia origin. In this study, we measured average body weight of 2,518
      Cynomolgus monkeys and analyzed hematology and serum biochemistry using 119
      males, and determined blood types in 642 monkeys with Cambodia origin. The
      average body weight of male Cynomolgus monkeys were 2.56+/-0.345 kg and female
      group was 2.43+/-0.330 kg at the age from 2 to 3 years. The male group showed
      relatively sharp increased average body weight from the 3 to 4 age period
      compared to the female group. In hematology and biochemistry, it was found that
      most of the data was similar when compared to other references even though some
      results showed differences. The ABO blood type result showed that type A, B, AB,
      and O was approximately 15.6, 33.3, 44.2, and 6.9%, respectively. The main blood
      type in this facility was B and AB. These biological background references of
      Cambodia origin could be used to provide important information to researchers who
      are using them in their biomedical research. 

PMID- 27051443
TI  - Comparison of the response using ICR mice derived from three different sources to
      ethanol/hydrochloric acid-induced gastric injury.
AB  - Animal models for gastric ulcers produced by physical, pharmacological and
      surgical methods have been widely employed to evaluate therapeutic drugs and
      investigate the mechanism of action of this disease. ICR mice were selected to
      produce this model, even though several mice and rats have been widely used in
      studies of gastric ulcers. To compare the responses of ICR mice obtained from
      three different sources to gastric ulcer inducers, alterations in gastric injury,
      histopathological structure, and inflammation were measured in Korl:ICR (Korea
      NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three
      concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid
      (HCl) solution. Firstly, the stomach lesion index gradually increased as the EtOH
      concentration increased in three ICR groups. Moreover, a significant increase in
      the level of mucosal injury, edema and the number of inflammatory cells was
      similarly detected in the EtOH/HCl treated group compared with the vehicle
      treated group in three ICR groups. Furthermore, the number of infiltrated mast
      cells and IL-1beta expression were very similar in the ICR group derived from
      three different sources, although some differences in IL-1beta expression were
      detected. Especially, the level of IL-1beta mRNA in 50 and 90EtOH/HCl treated
      group was higher in Korl:ICR and A:ICR than B:ICR. Overall, the results of this
      study suggest that Korl:ICR, A:ICR and B:ICR derived from different sources have
      an overall similar response to gastric ulcer induced by EtOH/HCl administration,
      although there were some differences in the magnitude of their responses. 

PMID- 27051444
TI  - Anticoccidial effects of the Plantago asiatica extract on experimental Eimeria
      tenella infection.
AB  - Anticoccidial effects of the Plantago asiatica extract (PAE) were evaluated in
      chickens following oral infection with Eimeria (E.) tenella. This study was
      conducted on the 3-day-old chickens (n=30). Those animals were divided with 3
      groups; PAE 0.1% treated/infected (n=10), PAE untreated/infected (n=10) and non
      infected control (n=10). Chickens were fed a standard diet supplemented with or
      without PAE for 1 week prior to infection with E. tenella (10,000 sporulated
      oocysts per chicken). The effects of PAE on E. tenella infection were assessed by
      two parameters; fecal oocysts shedding and body weights gain. The PAE-fed
      chickens produced significantly reduced fecal oocysts (P<0.05) when compared to
      the E. tenella-infected group fed standard diet. Also, PAE-based diet, improved
      body weight loss caused by E. tenella infection. Our data demonstrated that PAE
      had remarkable anticoccidial activities against E. tenella. This finding might
      have implications for the development of anticoccidial drug. This study is the
      first to demonstrate anticoccidial effect of PAE on Eimeria parasites. 

PMID- 27051445
TI  - Rapid and efficient identification of the mouse leptin receptor mutation
      (C57BL/KsJ-db/db) by tetra-primer amplification refractory mutation system
      polymerase chain reaction (ARMS-PCR) analysis.
AB  - The C57BLKS/J-Lepr(db) mouse has a point mutation in the leptin receptor gene and
      is one of the most useful animal model for non-insulin dependent diabetes
      mellitus in human. Since the homozygote of C57BLKS/J-Lepr(db) mouse is infertile,
      detection of point mutation in the leptin receptor gene is important for
      efficient maintaining strains as well as mass production of homozygotes. To
      develop a rapid and efficient genotyping method for C57BLKS/J-Lepr(db) mouse, the
      tetra-primer amplification-refractory mutation system polymerase chain reaction
      (ARMS-PCR) was used. The 407 and 199 bp PCR products were amplified from normal
      (+/+) mice; while the 407 and 268 bp PCR products were amplified from homozygotes
      (db/db) mice; and the 407, 268, and 199 bp PCR products were amplified from
      heterozygotes (db/+) mice. This result showed that the tetra-primer ARMS-PCR
      analysis by us is suitable to detect point mutation of the leptin receptor gene.
      Taken together, our method will dramatically reduce animal use for maintenance of
      strains as well as production of homozygote in the C57BLKS/J-Lepr(db) strains. 

PMID- 27051446
TI  - Pathomorphological features of calcinosis circumscripta in a dog.
AB  - A 19-month-old male German shepherd dog was presented with a hindlimb footpad
      mass. The mass was excised and histopathology was performed. Grossly, the cut
      section of the mass had multiple well-circumscribed nodules with a chalky
      appearance. Histopathologically, basophilic-stained calcium deposits of various
      sizes were distributed from dermis to subcutis, surrounded by epithelioid cells,
      multinucleated giant cells, and reactive fibroblasts. Myxoid metaplasia, calcium
      deposits in hair follicles, and psammoma-like bodies were also found. These
      histopathologic observations will greatly help to understand the pathogenesis of
      calcinosis circumscripta. 

PMID- 27051447
TI  - Confirmatory and Exploratory Factor Analysis for Validating the Phlegm Pattern
      Questionnaire for Healthy Subjects.
AB  - Background. Phlegm pattern questionnaire (PPQ) was developed to evaluate and
      diagnose phlegm pattern in Korean Medicine and Traditional Chinese Medicine, but
      it was based on a dataset from patients who visited the hospital to consult with
      a clinician regarding their health without any strict exclusion or inclusion. In
      this study, we reinvestigated the construct validity of PPQ with a new dataset
      and confirmed the feasibility of applying it to a healthy population. Methods.
      286 healthy subjects were finally included and their responses to PPQ were
      acquired. Confirmatory factor analysis (CFA) was conducted and the model fit was
      discussed. We extracted a new factor structure by exploratory factor analysis
      (EFA) and compared the two factor structures. Results. In CFA results, the model
      fit indices are acceptable (RMSEA = 0.074) or slightly less than the good fit
      values (CFI = 0.839, TLI = 0.860). Many average variances extracted were smaller
      than the correlation coefficients of the factors, which shows the somewhat
      insufficient discriminant validity. Conclusions. Through the results from CFA and
      EFA, this study shows clinically acceptable model fits and suggests the
      feasibility of applying PPQ to a healthy population with relatively good
      construct validity and internal consistency. 

PMID- 27051448
TI  - Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat
      Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer
      Cells.
AB  - Ginsenosides are the active components of Panax ginseng. Many research studies
      indicate that these deglycosylated, less-polar ginsenosides have better
      bioactivity than the major ginsenosides. In the present study, we sought to
      verify the enhanced anticancer effect of P. ginseng extract after undergoing the
      Maillard reaction as well as elucidate the underlying mechanism of action. The
      effects of 9 amino acids were tested; among them, the content of 20(S)-Rg3 in the
      ginseng extract increased to more than 30, 20, and 20% when processed with
      valine, arginine, and alanine, respectively, compared with that after normal heat
      processing. The ginseng extract that was heat-processed with arginine exhibited
      the most potent inhibitory effect on A2780 ovarian cancer cell proliferation.
      Therefore, the generation of 20(S)-Rg3 was suggested to be involved in this
      effect. Moreover, the inhibitory effect of 20(S)-Rg3 on A2780 cell proliferation
      was significantly stronger than that of 20(R)-Rg3. Protein expression levels of
      cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer
      cells markedly increased, whereas the expression of BID decreased after 20(S)-Rg3
      treatment. Therefore, we confirmed that the anticancer effects of the products of
      ginseng that was heat-processed with arginine are mediated mainly via the
      generation of the less-polar ginsenoside 20(S)-Rg3. 

PMID- 27051449
TI  - A Transmembrane Polymorphism of Fcgamma Receptor IIb Is Associated with Kidney
      Deficiency Syndrome in Rheumatoid Arthritis.
AB  - Objective. The purpose is to investigate the role of kidney deficiency and the
      association between kidney deficiency and a polymorphism FcgammaRIIb 695T>C
      coding for nonsynonymous substitution IIe232Thr (I232T) in rheumatoid arthritis
      (RA). Methods. Clinical parameters and autoantibodies were analyzed and
      genotyping was performed in 159 kidney deficiency and 161 non-kidney-deficiency
      RA patients. Results. The age of disease onset and disease duration exhibited
      significant differences between two groups (P < 0.01). Patients with kidney
      deficiency tend to have higher activity of disease (P < 0.05). Anti-cyclic
      citrullinated peptides antibodies (ACPA) levels of patients with kidney
      deficiency were higher than the controls (P = 0.039). 125 (78.6%) kidney
      deficiency and 114 (70.8%) non-kidney-deficiency patients had both ACPA-positive
      and RF-positive (P = 0.04, OR = 3.29). FcgammaRIIb I232TT homozygotes were
      identified in 10 of 159 (6.3%) kidney deficiency subjects and 1 of 161 (0.6%)
      controls (P = 0.000, OR = 16.45). Furthermore, in pooled genotype analysis,
      I232IT and I232TT homozygotes were significantly enriched in kidney deficiency
      individuals compared with the controls (P = 0.000, OR = 3.79). Frequency of T
      allele was associated with kidney deficiency RA population (P = 0.000, OR =
      3.18). Conclusion. This study confirmed that kidney deficiency was closely
      associated with disease activity and autoimmune disorder in RA. Kidney deficiency
      in RA is first to reveal a strong genetic link to FcgammaRIIb variants. 

PMID- 27051450
TI  - Effect of Dangguibohyul-Tang, a Mixed Extract of Astragalus membranaceus and
      Angelica sinensis, on Allergic and Inflammatory Skin Reaction Compared with
      Single Extracts of Astragalus membranaceus or Angelica sinensis.
AB  - Dangguibohyul-tang (DBT), herbal formula composed of Astragalus membranaceus (AM)
      and Angelica sinensis (AS) at a ratio of 5 : 1, has been used for the treatment
      of various skin diseases in traditional medicine. We investigated the effect of
      DBT on allergic and inflammatory skin reaction in atopic dermatitis-like model
      compared to the single extract of AM or AS. DBT treatment showed the remission of
      clinical symptoms, including decreased skin thickness and scratching behavior,
      the total serum IgE level, and the number of mast cells compared to DNCB group as
      well as the single extract of AM- or AS-treated group. Levels of cytokines (IL-4,
      IL-6, IFN-gamma, TNF-alpha, and IL-1beta) and inflammatory mediators (NF-kappaB,
      phospho-IkappaBalpha, and phospho-MAPKs) were significantly decreased in AM, AS,
      and DBT groups. These results demonstrated that AM, AS, and DBT may have the
      therapeutic property on atopic dermatitis by inhibition of allergic and
      inflammatory mediators and DBT formula; a mixed extract of AM and AS based on the
      herb pairs theory especially might be more effective on antiallergic reaction as
      compared with the single extract of AM or AS. 

PMID- 27051451
TI  - A Systematic Review on the Effects of Botanicals on Skeletal Muscle Health in
      Order to Prevent Sarcopenia.
AB  - We performed a systematic review to evaluate the evidence-based medicine
      regarding the main botanical extracts and their nutraceutical compounds
      correlated to skeletal muscle health in order to identify novel strategies that
      effectively attenuate skeletal muscle loss and enhance muscle function and to
      improve the quality of life of older subjects. This review contains all eligible
      studies from 2010 to 2015 and included 57 publications. We focused our attention
      on effects of botanical extracts on growth and health of muscle and divided these
      effects into five categories: anti-inflammation, muscle damage prevention,
      antifatigue, muscle atrophy prevention, and muscle regeneration and
      differentiation. 

PMID- 27051452
TI  - Inhibition of alpha-Glucosidase by Thiosulfinate as a Target for Glucose
      Modulation in Diabetic Rats.
AB  - Postprandial hyperglycemia is a predisposing factor for vascular dysfunction and
      organ damage. alpha-glucosidase is a hydrolytic enzyme that increases the glucose
      absorption rate and subsequently elevates blood glucose levels. Garlic (Allium
      sativum L.) is a rich source of several phytonutrients, including thiosulfinate
      (THIO). The aim of this study was to evaluate the ability of THIO, a potent
      inhibitor of intestinal alpha-glucosidase, to reduce postprandial blood glucose.
      Male albino rats were randomly assigned to five different groups (n = 10/group).
      Group 1 served as the control group. Groups 2-5 were injected intraperitoneally
      with a single dose of streptozotocin (STZ) to induce diabetes. Group 2 comprised
      untreated diabetic rats. Groups 3 and 4 contained diabetic rats that were given
      THIO orally (20 mg/kg body weight/day and 40 mg/kg body weight/day, resp.). Group
      5 was the positive control having diabetic rats treated orally with acarbose (10
      mg/kg body weight/day; positive control). Diabetic rats treated with THIO
      displayed a significant blood glucose reduction (p < 0.001 and < 0.01 by analysis
      of variance, resp.) and a significant elevation in insulin compared with that of
      untreated rats. THIO is an effective noncompetitive intestinal alpha-glucosidase
      inhibitor that promotes hypoglycemic action (p < 0.001) in STZ-injected rats.
      THIO is a promising agent for the management of postprandial hyperglycemia. 

PMID- 27051453
TI  - Anti-HMG-CoA Reductase, Antioxidant, and Anti-Inflammatory Activities of
      Amaranthus viridis Leaf Extract as a Potential Treatment for
      Hypercholesterolemia.
AB  - Inflammation and oxidative stress are believed to contribute to the pathology of
      several chronic diseases including hypercholesterolemia (elevated levels of
      cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant
      origin are needed as synthetic drugs, such as statins, which are known to cause
      adverse effects on the liver and muscles. Amaranthus viridis (A. viridis) has
      been used from ancient times for its supposedly medically beneficial properties.
      In the current study, different parts of A. viridis (leaf, stem, and seed) were
      evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti
      inflammatory activities. The putative HMG-CoA reductase inhibitory activity of A.
      viridis extracts at different concentrations was determined
      spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate. A. viridis
      leaf extract revealed the highest HMG-CoA reductase inhibitory effect at about
      71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf
      extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl
      (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations. A.
      viridis leaf extract was proven to be an effective inhibitor of hyaluronidase,
      lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest that A.
      viridis leaf extract is a source of potent antioxidant and anti-inflammatory
      agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase.

PMID- 27051454
TI  - Effect of Laser Acupuncture on Anthropometric Measurements and Appetite
      Sensations in Obese Subjects.
AB  - Purpose. A patient-assessor-blinded, randomized, sham-controlled crossover trial
      was performed to investigate the effectiveness of laser acupuncture on
      anthropometric measurements and appetite sensation in obese subjects. Methods.
      Fifty-two obese subjects were randomly assigned to either the laser acupuncture
      group or the sham laser acupuncture group. Subjects within each group received
      the relevant treatment three times a week for 8 weeks. After a two-week washout
      period, the subjects then received the treatment of the opposite group for
      another 8 weeks. BMI, body fat percentage, waist-to-hip ratio (WHR), waist
      circumference, hip circumference, and appetite sensations were measured before
      and after 8 weeks of treatment. Results. BMI, body fat percentage, WHR, waist
      circumference, and hip circumference decreased significantly (p < 0.05) in the
      laser acupuncture group compared to baseline but there was no decrease in those
      variables in the sham laser acupuncture group. Laser acupuncture significantly
      improved scores on the fullness, hunger, satiety, desire to eat, and overall well
      being relative to the baseline (p < 0.05). Conclusions. Laser acupuncture is well
      tolerated and improves anthropometric measurements and appetite sensations in
      obese subjects. 

PMID- 27051455
TI  - Stress and Fatigue Management Using Balneotherapy in a Short-Time Randomized
      Controlled Trial.
AB  - Objective. To investigate the influence of high-salinity geothermal mineral water
      on stress and fatigue. Method. 180 seamen were randomized into three groups:
      geothermal (65), music (50), and control (65). The geothermal group was
      administered 108 g/L salinity geothermal water bath for 2 weeks five times a
      week. Primary outcome was effect on stress and fatigue. Secondary outcomes were
      the effect on cognitive function, mood, and pain. Results. The improvements after
      balneotherapy were a reduction in the number and intensity of stress-related
      symptoms, a reduction in pain and general, physical, and mental fatigue, and an
      improvement in stress-related symptoms management, mood, activation, motivation,
      and cognitive functions with effect size from 0.8 to 2.3. In the music therapy
      group, there were significant positive changes in the number of stress symptoms,
      intensity, mood, pain, and activity with the effect size of 0.4 to 1.1. The
      researchers did not observe any significant positive changes in the control
      group. The comparison between the groups showed that balneotherapy was superior
      to music therapy and no treatment group. Conclusions. Balneotherapy is beneficial
      for stress and fatigue reduction in comparison with music or no therapy group.
      Geothermal water baths have a potential as an efficient approach to diminish
      stress caused by working or living conditions. 

PMID- 27051456
TI  - Alanine-fortified tomatoes relieve the acute alcohol-induced adverse effects in
      healthy men: a randomized cross-over study.
AB  - BACKGROUND: Little is known about the effects of dietary components on the
      regulation of the gastric emptying rate of alcohol and its impact on alcohol
      metabolism. We recently found that the crude water-insoluble dietary fibers from
      several types of botanical foods maintained aqueous ethanol solutions.
      Additionally, the ethanol-absorbing ability of the dietary fibers correlated with
      the inhibition of the blood ethanol elevation by delaying gastric emptying.
      Moreover, we found that the synergism between tomatoes and alanine to reduce the
      absorption of alcohol in rats was attributable to the effect of alanine on
      precipitates, such as the crude water-insoluble dietary fibers of tomatoes. In
      the present study, we assess whether an alanine-fortified tomato (AFT) is
      effective in relieving acute alcohol-induced adverse effects by lowering the
      alcohol action in healthy human volunteers following the ingestion of alcohol
      with a meal. METHODS: Twenty healthy males ingested the AFT or sugar as the
      control, with 1.2 g/kg of alcohol and a micronutrient-fortified meal in a
      randomized cross-over study. Breath alcohol concentrations were temporally
      measured, and blood and urine samples were obtained during the trial. The study
      protocol was repeated with the AFT and sugar groups reversed 4 weeks later.
      RESULTS: Various analyses were performed using the data from the 15 subjects. The
      breath alcohol concentrations significantly decreased when AFT was ingested. A
      decrease in the urinary pH was also noted following the ingestion of AFT.
      Moreover, the sum of seven sedative scores as subjective sensation after alcohol
      ingestion was significantly reduced by AFT the next morning. CONCLUSIONS: Our
      study demonstrates that the simultaneous ingestion of AFT under the consumption
      of excess alcohol and a micronutrient-fortified meal relieved the acute alcohol
      induced adverse effects in male volunteers. These results are consistent with the
      effectiveness observed in rats as previously reported.

PMID- 27051457
TI  - Reappraisal of waist circumference cutoff value according to general obesity.
AB  - BACKGROUND: Current criterion of waist circumference (WC) for abdominal obesity
      is not enough to demonstrate characteristics of obese and non-obese populations
      defined by BMI. The aim of this study was to redefine the cutoff values of WC
      according to general obesity (BMI >= 25 kg/m(2)). METHODS: The receiver operating
      characteristic curve analysis was performed to determine cutoff values of WC for
      predicting atherosclerosis according to BMI in 1,063 non-diabetic subjects. To
      validate this new criterion, diabetic patients (n = 3,690) were divided into
      three groups based on the current (WC of 90/80 cm for men/women) and new cutoff
      values of WC: 1) group with WC below the lowest value of two criteria; 2)
      intermediate group defined as having a WC between them; and 3) group with WC more
      than the highest value of them. RESULTS: The new cutoff values of WC for
      predicting atherosclerosis in non-diabetic subjects were 84/76 cm for non-obese
      men/women, and 93/87 cm for obese men/women, respectively. Of non-obese diabetic
      patients, the intermediate group (WC 84 ~ 90/76 ~ 80 cm for men/women) was more
      insulin resistant and showed elevated odds ratio (OR) for having 2 or more
      metabolic risk factors compared to group with WC below 84/76 cm for men/women [OR
      2.48 (95 % CI 1.89-3.25) in men, 2.01 (95% CI 1.45-2.78) in women]. In contrast,
      among obese diabetic patients, insulin resistance and the likelihood of having 2
      or more metabolic risk factors were not different from the intermediate group (WC
      90 ~ 93/80 ~ 87 cm for men/women) and group with WC below 90/80 cm for men/women.
      CONCLUSIONS: The current universal cutoff values of WC may under- or over
      estimate the metabolic risks of intermediate groups. Therefore, the WC criteria
      for abdominal obesity should be applied differently depending on the BMI.

PMID- 27051458
TI  - Awareness of occupational hazards and associated factors among welders in Lideta
      Sub-City, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Welding is a manufacturing industry where workers could be exposed to
      several hazards. However, there is a dearth of studies clarifying the situation
      in Ethiopia. The present study determined the level of awareness of occupational
      hazards and associated factors among welding employees at Lideta Sub-City, Addis
      Ababa, Ethiopia. METHODS: A work site-based cross-sectional study was conducted
      among welding employees Lideta Sub-City, Addis Ababa, Ethiopia from April to May
      2015. Stratified sampling followed by simple random sampling techniques was used
      to select the study participants. A pilot tested and structured questionnaire was
      used to collect data. Multivariable analyses were employed to see the effect of
      explanatory variables on workers' awareness of occupational hazards. RESULTS:
      According to our criteria of awareness 86.5 % of surveyed workers were aware of
      occupational hazards. A higher work experience, presence of work regulation, job
      satisfaction, being married, being single, and a higher educational status were
      factors significantly associated with workers' awareness of occupational hazards.
      CONCLUSION: This study revealed that the level of awareness of occupational
      hazards among welders was high. However, this does not mean that there will be no
      need for further strengthening of the safety measures as significant proportions
      of the workers still had low awareness. Interventions to boost workers awareness
      of occupational hazards should focus on areas, such as provision of safety
      trainings, promotion of safety advocacy, and enforcement of appropriate workplace
      safety regulation.

PMID- 27051459
TI  - Use of a Novel Grammatical Inference Approach in Classification of Amyloidogenic
      Hexapeptides.
AB  - The present paper is a novel contribution to the field of bioinformatics by using
      grammatical inference in the analysis of data. We developed an algorithm for
      generating star-free regular expressions which turned out to be good
      recommendation tools, as they are characterized by a relatively high correlation
      coefficient between the observed and predicted binary classifications. The
      experiments have been performed for three datasets of amyloidogenic hexapeptides,
      and our results are compared with those obtained using the graph approaches, the
      current state-of-the-art methods in heuristic automata induction, and the support
      vector machine. The results showed the superior performance of the new
      grammatical inference algorithm on fixed-length amyloid datasets. 

PMID- 27051460
TI  - Influence of PEEK Coating on Hip Implant Stress Shielding: A Finite Element
      Analysis.
AB  - Stress shielding is a well-known failure factor in hip implants. This work
      proposes a design concept for hip implants, using a combination of metallic stem
      with a polymer coating (polyether ether ketone (PEEK)). The proposed design
      concept is simulated using titanium alloy stems and PEEK coatings with
      thicknesses varying from 100 to 400 MUm. The Finite Element analysis of the
      cancellous bone surrounding the implant shows promising results. The effective
      von Mises stress increases between 81 and 92% for the complete volume of
      cancellous bone. When focusing on the proximal zone of the implant, the increased
      stress transmission to the cancellous bone reaches between 47 and 60%. This
      increment in load transferred to the bone can influence mineral bone loss due to
      stress shielding, minimizing such effect, and thus prolonging implant lifespan. 

PMID- 27051461
TI  - A Stochastic Differential Equation Model for the Spread of HIV amongst People Who
      Inject Drugs.
AB  - We introduce stochasticity into the deterministic differential equation model for
      the spread of HIV amongst people who inject drugs (PWIDs) studied by Greenhalgh
      and Hay (1997). This was based on the original model constructed by Kaplan (1989)
      which analyses the behaviour of HIV/AIDS amongst a population of PWIDs. We derive
      a stochastic differential equation (SDE) for the fraction of PWIDs who are
      infected with HIV at time. The stochasticity is introduced using the well-known
      standard technique of parameter perturbation. We first prove that the resulting
      SDE for the fraction of infected PWIDs has a unique solution in (0, 1) provided
      that some infected PWIDs are initially present and next construct the conditions
      required for extinction and persistence. Furthermore, we show that there exists a
      stationary distribution for the persistence case. Simulations using realistic
      parameter values are then constructed to illustrate and support our theoretical
      results. Our results provide new insight into the spread of HIV amongst PWIDs.
      The results show that the introduction of stochastic noise into a model for the
      spread of HIV amongst PWIDs can cause the disease to die out in scenarios where
      deterministic models predict disease persistence. 

PMID- 27051462
TI  - Erratum to: Reduced health-related quality of life among Japanese college
      students with visual impairment.
AB  - [This corrects the article DOI: 10.1186/s13030-015-0045-1.]. 

PMID- 27051463
TI  - Violent events, ward climate and ideas for violence prevention among nurses in
      psychiatric wards: a focus group study.
AB  - BACKGROUND: Patient violence against nurses in their work environments is a
      widespread global concern, particularly in the field of mental health care. A
      high prevalence of violent events impacts the well-being of nurses and may also
      impair overall ward climate. However, it has been proposed that nurses' use
      limited techniques to prevent patient violence, and, therefore, more
      comprehensive methods for dealing with patient violence are needed. There is
      still restricted understanding of the ward climate during the occurrence of a
      violent event as well as how these incidents could be more effectively prevented.
      This study aimed to explore nurses' experiences of violent events in psychiatric
      wards, give insight into ward climates and examine suggestions for violence
      prevention. METHODS: This study employed a descriptive, exploratory design
      including focus groups (n = 5) and open-ended questions. The participants were
      registered and enrolled nurses (n = 22) working on three closed psychiatric in
      patient wards in one Finnish hospital district. Focus groups were tape-recorded,
      transcribed and analyzed with inductive content analysis. RESULTS: Nurses'
      experiences of violent events included a variety of warning signs and high-risk
      situations which helped them to predict forthcoming violence. Patient-instigated
      violent events were described as complicated situations involving both nurses and
      patients. When the wards were overloaded with work or emotions, or if nurses had
      become cynical from dealing with such events, well-being of nurses was impaired
      and nursing care was complicated. Suggestions for violence prevention were
      identified, and included, for example, more skilled interaction between nurses
      and patients and an increase in contact between nurses and patients on the ward.
      CONCLUSIONS: This study revealed the complexity of violent events on psychiatric
      wards as well as the implications of these events on clinical practice
      development and training, administration and policy. A routine process is needed
      through which nurses' experiences and ideas concerning prevention of violent
      events are acknowledged.

PMID- 27051464
TI  - Managing mental illness in Ghana: the state of commonly prescribed psychotropic
      medicines.
AB  - BACKGROUND: In Ghana, about 13 % of the adult population is estimated to be
      affected by mental health disorders of varying forms. In managing these patients,
      psychotropic medications are mostly employed. Since most of these conditions are
      chronic cases, the medications are consumed for prolonged periods of time.
      However, there exists an absence of information on efficacy, side effects,
      accessibility and prescription practices of psychotropic medication utilization
      from the viewpoint of the practitioners who are primarily involved in
      prescribing, dispensing and administering these medications. METHOD: Qualitative
      study composed of semi-structured interviews were conducted with twenty three
      (23) participants from Accra psychiatry, Pantang and Ankaful hospitals. These
      were fifteen (15) nurses, six (6) clinicians and two (2) pharmacists. All
      interviews were recorded digitally and analyzed thematically. RESULTS: The
      commonly prescribed psychotropic medications were grouped into four classes.
      These were antipsychotics, antidepressants, anticonvulsants and hypnosedatives.
      Although each facility had at least one drug belonging to each class, there were
      frequent shortages recorded across the board. Also, drugs were free when supplied
      by government, and expensive when obtained from outside. When subsidized, the
      average cost of a day's supply of the most common antipsychotic was 4 % of the
      daily minimum wage. The procurement system for the medications was fraught with
      challenges such as inadequate financing, poor procurement practices and
      bureaucracies with the process which affected the availability and quality of
      medications. CONCLUSION: The commonly prescribed psychotropic medications are in
      conformity with the recommendations of the WHO guidelines and the standard
      treatment guidelines of Ghana. However, the accessibility and quality of
      medications in the sector are inadequate. To improve mental health services in
      the country, it is important to ensure the adequate and regular provision of
      quality medicines in the mental health sector.

PMID- 27051465
TI  - Distinguishing highly similar gene isoforms with a clustering-based
      bioinformatics analysis of PacBio single-molecule long reads.
AB  - BACKGROUND: Gene isoforms are commonly found in both prokaryotes and eukaryotes.
      Since each isoform may perform a specific function in response to changing
      environmental conditions, studying the dynamics of gene isoforms is important in
      understanding biological processes and disease conditions. However, genome-wide
      identification of gene isoforms is technically challenging due to the high degree
      of sequence identity among isoforms. Traditional targeted sequencing approach,
      involving Sanger sequencing of plasmid-cloned PCR products, has low throughput
      and is very tedious and time-consuming. Next-generation sequencing technologies
      such as Illumina and 454 achieve high throughput but their short read lengths are
      a critical barrier to accurate assembly of highly similar gene isoforms, and may
      result in ambiguities and false joining during sequence assembly. More recently,
      the third generation sequencer represented by the PacBio platform offers
      sufficient throughput and long reads covering the full length of typical genes,
      thus providing a potential to reliably profile gene isoforms. However, the PacBio
      long reads are error-prone and cannot be effectively analyzed by traditional
      assembly programs. RESULTS: We present a clustering-based analysis pipeline
      integrated with PacBio sequencing data for profiling highly similar gene
      isoforms. This approach was first evaluated in comparison to de novo assembly of
      454 reads using a benchmark admixture containing 10 known, cloned msg genes
      encoding the major surface glycoprotein of Pneumocystis jirovecii. All 10 msg
      isoforms were successfully reconstructed with the expected length (~1.5 kb) and
      correct sequence by the new approach, while 454 reads could not be correctly
      assembled using various assembly programs. When using an additional benchmark
      admixture containing 22 known P. jirovecii msg isoforms, this approach accurately
      reconstructed all but 4 these isoforms in their full-length (~3 kb); these 4
      isoforms were present in low concentrations in the admixture. Finally, when
      applied to the original clinical sample from which the 22 known msg isoforms were
      cloned, this approach successfully identified not only all known isoforms
      accurately (~3 kb each) but also 48 novel isoforms. CONCLUSIONS: PacBio
      sequencing integrated with the clustering-based analysis pipeline achieves high
      throughput and high-resolution discrimination of highly similar sequences, and
      can serve as a new approach for genome-wide characterization of gene isoforms and
      other highly repetitive sequences.

PMID- 27051466
TI  - Associations and prognostic implications of Eastern Cooperative Oncology Group
      performance status and tumoral LINE-1 methylation status in stage III colon
      cancer patients.
AB  - BACKGROUND: Low methylation status of LINE-1 in tumors is associated with poor
      survival in patients with colon cancer. Eastern Cooperative Oncology Group
      performance status (ECOG-PS) is a method to assess the functional status of a
      patient. We retrospectively evaluated the relationship between ECOG-PS and LINE-1
      methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or
      colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin
      (FOLFOX). RESULTS: LINE-1 methylation and microsatellite instability were
      analyzed in stage III or high-risk stage II CRCs (n = 336). LINE-1 methylation
      levels were correlated with clinicopathological features, including PS and
      recurrence-free survival (RFS). The association between the tumoral LINE-1
      methylation level and PS was observed (OR = 2.56, P < 0.001). Differences in LINE
      1 methylation levels in cancer tissue between the PS 0 and 1 groups were
      significant in patients older than 60 years (P = 0.001), the overweight body mass
      index group (P = 0.005), and the stage III disease group (P = 0.008). Prognostic
      significances of LINE-1 methylation status or combined PS and LINE-1 methylation
      statuses were identified in stage III colon cancers, not in stage III and high
      risk stage II CRCs. Low LINE-1 methylation status was closely associated with a
      shorter RFS time. The difference between PS(0)/LINE-1(high) and PS(>=1)/LINE
      1(low) was significant, which suggests that colon cancer patients with concurrent
      PS(>=1)/LINE-1 (low) have a higher recurrence rate. CONCLUSIONS: PS was
      associated with LINE-1 methylation in CRC tissue. LINE-1 methylation was
      associated with RFS in stage III colon cancer patients who were treated with
      adjuvant FOLFOX chemotherapy. Combined PS and LINE-1 methylation status might
      serve as a useful predictor of cancer recurrence.

PMID- 27051467
TI  - TREM2 upregulation correlates with 5-hydroxymethycytosine enrichment in
      Alzheimer's disease hippocampus.
AB  - BACKGROUND: Recent genome-wide association studies revealed TREM2 rs75932628-T
      variant to be associated with Alzheimer's disease (AD) and other
      neurodegenerative diseases. However, the role that TREM2 plays in sporadic AD is
      largely unknown. Our aim was to assess messenger RNA (mRNA) expression levels and
      DNA methylation profiling of TREM2 in human hippocampus in AD brain. We measured
      TREM2 mRNA levels in the hippocampus in a cohort of neuropathologically confirmed
      controls and pure AD cases showing no other protein deposits than beta-amyloid
      and phosphorylated tau. We also examined DNA methylation levels in the TREM2
      transcription start site (TSS)-associated region by bisulfite cloning sequencing
      and further extended the study by measuring 5-hydroxymethycytosine (5hmC)
      enrichment at different regions of TREM2 by 5hmC DNA immunoprecipitation combined
      with real-time qPCR. RESULTS: A 3.4-fold increase in TREM2 mRNA levels was
      observed in the hippocampus of AD cases compared to controls (p = 1.1E-05).
      Interestingly, TREM2 methylation was higher in AD cases compared to controls
      (76.2 % +/- 15.5 versus 57.9 % +/- 17.1; p = 0.0016). Moreover, TREM2 mRNA levels
      in the AD hippocampus correlated with enrichment in 5hmC at the TREM2 gene body
      (r = 0.771; p = 0.005). CONCLUSIONS: TREM2 mRNA levels are increased in the human
      hippocampus in AD cases compared to controls. DNA methylation, and particularly
      5hmC, may be involved in regulating TREM2 mRNA expression in the AD brain.
      Further studies are guaranteed to investigate in depth the role of 5hmC in AD and
      other neurodegenerative disorders.

PMID- 27051468
TI  - Elasto-inertial particle focusing under the viscoelastic flow of DNA solution in
      a square channel.
AB  - Particle focusing is an essential step in a wide range of applications such as
      cell counting and sorting. Recently, viscoelastic particle focusing, which
      exploits the spatially non-uniform viscoelastic properties of a polymer solution
      under Poiseuille flow, has attracted much attention because the particles are
      focused along the channel centerline without any external force. Lateral particle
      migration in polymer solutions in square channels has been studied due to its
      practical importance in lab-on-a-chip applications. However, there are still many
      questions about how the rheological properties of the medium alter the
      equilibrium particle positions and about the flow rate ranges for particle
      focusing. In this study, we investigated lateral particle migration in a
      viscoelastic flow of DNA solution in a square microchannel. The elastic property
      is relevant due to the long relaxation time of a DNA molecule, even when the DNA
      concentration is extremely low. Further, the shear viscosity of the solution is
      essentially constant irrespective of shear rate. Our current results demonstrate
      that the particles migrate toward the channel centerline and the four corners of
      a square channel in the dilute DNA solution when the inertia is negligible
      (elasticity-dominant flow). As the flow rate increases, the multiple equilibrium
      particle positions are reduced to a single file along the channel centerline, due
      to the elasto-inertial particle focusing mechanism. The current results support
      that elasto-inertial particle focusing mechanism is a universal phenomenon in a
      viscoelastic fluid with constant shear viscosity (Boger fluid). Also, the
      effective flow rate ranges for three-dimensional particle focusing in the DNA
      solution were significantly higher and wider than those for the previous
      synthetic polymer solution case, which facilitates high throughput analysis of
      particulate systems. In addition, we demonstrated that the DNA solution can be
      applied to focus a wide range of particle sizes in a single channel and also
      align red blood cells without any significant deformation. 

PMID- 27051469
TI  - One step antibody-mediated isolation and patterning of multiple cell types in
      microfluidic devices.
AB  - Cell-cell interactions play a key role in regeneration, differentiation, and
      basic tissue function taking place under physiological shear forces. However,
      current solutions to mimic such interactions by micro-patterning cells within
      microfluidic devices have low resolution, high fabrication complexity, and are
      limited to one or two cell types. Here, we present a microfluidic platform
      capable of laminar patterning of any biotin-labeled peptide using streptavidin
      based surface chemistry. The design permits the generation of arbitrary cell
      patterns from heterogeneous mixtures in microfluidic devices. We demonstrate the
      robust co-patterning of alpha-CD24, alpha-ASGPR-1, and alpha-Tie2 antibodies for
      rapid isolation and co-patterning of mixtures of hepatocytes and endothelial
      cells. In addition to one-step isolation and patterning, our design permits step
      wise patterning of multiple cell types and empty spaces to create complex
      cellular geometries in vitro. In conclusion, we developed a microfluidic device
      that permits the generation of perfusable tissue-like patterns in microfluidic
      devices by directly injecting complex cell mixtures such as differentiated stem
      cells or tissue digests with minimal sample preparation. 

PMID- 27051470
TI  - A fluid collection system for dermal wounds in clinical investigations.
AB  - In this work, we demonstrate the use of a thin, self adherent, and clinically
      durable patch device that can collect fluid from a wound site for analysis. This
      device is manufactured from laminated silicone layers using a novel all-silicone
      double-molding process. In vitro studies for flow and delivery were followed by a
      clinical demonstration for exudate collection efficiency from a clinically
      presented partial thickness burn. The demonstrated utility of this device lends
      itself for use as a research implement used to clinically sample wound exudate
      for analysis. This device can serve as a platform for future integration of
      wearable technology into wound monitoring and care. The demonstrated fabrication
      method can be used for devices requiring thin membrane construction. 

PMID- 27051471
TI  - Electrical lysis of cells for detergent-free droplet assays.
AB  - Efficient lysis is critical when analyzing single cells in microfluidic droplets,
      but existing methods utilize detergents that can interfere with the assays to be
      performed. We demonstrate robust cell lysis without the use of detergents or
      other chemicals. In our method, cells are exposed to electric field immediately
      before encapsulation in droplets, resulting in cell lysis. We characterize lysis
      efficiency as a function of control parameters and demonstrate compatibility with
      enzymatic assays by measuring the catalysis of beta-glucosidase, an important
      cellulase used in the conversion of biomass to biofuel. Our method enables assays
      in microfluidic droplets that are incompatible with detergents. 

PMID- 27051472
TI  - Ecotoxicity assessment using ciliate cells in millifluidic droplets.
AB  - Precise analysis of the aquatic cells and their responses to the toxic chemicals,
      i.e., water disinfective agents, is of crucial importance due to their role in
      the ecosystem. We demonstrate the application of the droplets based millifluidic
      tool for isolating and longtime monitoring of single Paramecium tetraurelia cells
      using a large number of water-in-oil emulsion droplets. Due to the automated
      monitoring of the fluorescence signal, the droplets containing cells are
      distinguished from the empty reservoirs. A viability indicator is used to follow
      the metabolic dynamic of the cells in every single droplet. Finally, we perform
      ecotoxicity tests in droplets, exposing the encapsulated paramecia cells to
      silver nitrate for determination of EC50 levels, and compare the output with the
      conventional microtiter plate assay. 

PMID- 27051473
TI  - [Acute otitis media complicated with pneumocephalus and pneumococcal meningitis].

PMID- 27051474
TI  - Tanshinol Rescues the Impaired Bone Formation Elicited by Glucocorticoid Involved
      in KLF15 Pathway.
AB  - Decreased bone formation is responsible for the pathogenesis of glucocorticoid-
      (GC-) induced osteoporosis (GIO), while the mechanism remains to be elucidated.
      The aim was to investigate how natural antioxidant tanshinol attenuates oxidative
      stress and rescues impaired bone formation elicited by GC in Sprague-Dawley rats
      and in C2C12 cells and/or MC3T3-E1 cells. The results showed that tanshinol
      prevented bone loss and decreased biomechanical characteristics and suppressed
      reduction of biomarkers related to osteogenesis in GIO rats. Further study
      revealed that tanshinol reversed decrease of transcription activity of Osterix
      luc and rescued impairment of osteoblastic differentiation and bone formation
      involved in induction of KLF15 mRNA. Meanwhile, tanshinol diminished inhibition
      of protein expression of beta-catenin and Tcf4 and transcription activity of Tcf4
      luc induced by GC, especially under conditions of KLF siRNA in vitro.
      Additionally, tanshinol attenuated increase of reactive oxygen species (ROS)
      generation, phosphorylation of p66(Shc) expression, TUNEL-positive cells, and
      caspase-3 activity elicited by KLF15 under conditions of GC. Taken together, the
      present findings suggest that tanshinol attenuated the decrease of bone formation
      and bone mass and bone quality elicited by GC involved in KLF15/Wnt signaling
      transduction and counteracted GC-evoked oxidative stress and subsequent cell
      apoptosis involved in KLF15/p66(Shc) pathway cascade. 

PMID- 27051475
TI  - Antioxidant, Antibacterial, and Cytotoxic Activities of the Ethanolic Origanum
      vulgare Extract and Its Major Constituents.
AB  - Oregano is a perennial shrub that grows in the mountains of the Mediterranean and
      Euro/Irano-Siberian regions. This study was conducted to identify the major
      constituents of the ethanolic Origanum vulgare extract and examine the cytotoxic,
      antioxidant, and antibacterial properties of the extract but more importantly the
      contribution of its specific major constituent(s) or their combination to the
      overall extract biological activity. Gas chromatography/mass spectroscopy
      analysis showed that the extract contained monoterpene hydrocarbons and phenolic
      compounds, the major ones being carvacrol and thymol and to a lesser extent p
      cymene, 1-octacosanol, creosol, and phytol. A549 epithelial cells challenged with
      the extract showed a concentration-dependent increase in cytotoxicity. A
      combination of thymol and carvacrol at equimolar concentrations to those present
      in the extract was less cytotoxic. The A549 cells pretreated with nonlethal
      extract concentrations protected against hydrogen-peroxide-induced cytotoxicity,
      an antioxidant effect more effective than the combination of equimolar
      concentrations of thymol/carvacrol. Inclusion of p-cymene and/or 1-octacosanol
      did not alter the synergistic antioxidant effects of the carvacrol/thymol
      mixture. The extract also exhibited antimicrobial properties against Gram
      positive and Gram-negative bacterial strains including clinical isolates. In
      conclusion, the oregano extract has cytotoxic, antioxidant, and antibacterial
      activities mostly attributed to carvacrol and thymol. 

PMID- 27051476
TI  - Carcinoma of the lip five years after bone marrow transplantation.

PMID- 27051477
TI  - Need for Refinement of International Retinopathy of Prematurity Guidelines and
      Classifications.

PMID- 27051478
TI  - Corneal Changes After Collagen Crosslinking for Keratoconus Using Dual
      Scheimpflug Imaging.
AB  - PURPOSE: To evaluate corneal changes after collagen crosslinking (CXL) therapy
      for keratoconus (KCN) using the Galilei dual Scheimpflug analyzer. METHODS: This
      prospective, nonrandomized clinical study included 35 eyes of 32 keratoconus
      patients who had undergone CXL. The eyes were saturated with riboflavin solution
      and were subjected for 30 minutes to ultraviolet-A (UV-A) light with irradiance
      of 3 mW/cm(2). Effectiveness of the treatment was assessed by measuring
      uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), manifest
      cylinder/sphere, keratometry, pachymetry, posterior and anterior elevations by
      the Galilei dual Scheimpflug analyzer. Prior to treatment and 8 months after
      therapy, Scheimpflug analysis was performed using the Galilei system. The four
      sets of data including keratometry values, pachymetry, elevation parameters and
      surface indices were statistically analyzed and compared. RESULTS: Mean patient
      age was 22.3 +/- 3.8 years and mean postoperative follow-up was 8.1 +/- 3.2
      months. There was a significant increase in UCVA (0.54 +/- 0.35 Log MAR
      preoperatively to 0.49 +/- 0.34 LogMAR postoperatively, P = 0.01) and BCVA (0.21
      +/- 0.19 Log MAR preoperatively to 0.16 +/- 0.17 LogMAR postoperatively, P =
      0.01). Mean cycloplegic spherical equivalent refractive error was -4.13 +/- 2.65
      Diopter (D) preoperatively and - 4.67 +/- 2.96 D postoperatively (P < 0.001).
      During the follow-up period, no significant difference was observed in
      pachymetric and elevation data postoperatively. CONCLUSION: Corneal stabilization
      could be achieved by collagen crosslinking therapy for keratoconus in terms of
      corneal thickness, keratometry values, elevation parameters and surface indices.

PMID- 27051479
TI  - Effect of Donor Graft Quality on Clinical Outcomes After Penetrating Keratoplasty
      for Keratoconus.
AB  - PURPOSE: To evaluate the effect of donor and eye bank characteristics on graft
      rating and clinical outcomes after penetrating keratoplasty (PK) for keratoconus.
      METHODS: This retrospective interventional case series included 252 keratoconic
      eyes which underwent PK. Donor data included age and sex, cause of death, death
      to-preservation time, preservation-to-surgery time, epithelial and stromal
      status, endothelial cell density (ECD) and morphology, and graft rating.
      Postoperative outcomes included visual acuity, refractive error, epithelial
      problems, suture-related complications, graft rejection, and graft transparency.
      Multivariate regression analysis assessed correlations between donor and eye bank
      characteristics and graft quality, and postoperative outcomes. RESULTS: Mean
      recipient and donor age was 29.7 +/- 10.0 and 26.2 +/- 8.8 years, respectively
      and mean follow-up period was 66.7 +/- 38.5 months. Death-to-preservation time
      was significantly associated with the presence of graft epithelial sloughing (P =
      0.005) and stromal cloudiness (P < 0.001). Donor age significantly influenced ECD
      (P = 0.02), mean cell area (P = 0.04), and hexagonality (P = 0.01). The presence
      of epithelial defects on postoperative day 1 correlated significantly with death
      to-preservation time (P = 0.004). Graft stromal edema on postoperative day 1 was
      significantly associated with graft epithelial sloughing (P < 0.001).
      Postoperative visual and refractive outcomes, complications, and graft survival
      were not correlated with any donor or eye bank factors. CONCLUSION: Donor and eye
      bank variables affected the quality of donor corneas and early postoperative
      course. However, their long term effect on clinical outcomes, complications, and
      graft survival were insignificant.

PMID- 27051480
TI  - Visual and Refractive Outcomes of Phacoemulsification with Implantation of
      Accommodating versus Standard Monofocal Intraocular Lenses.
AB  - PURPOSE: To compare distant and near visual function after cataract surgery with
      implantation of Crystalens HD or Tek-Clear as accommodating intraocular lenses
      (IOLs), versus SA60AT as a standard IOL. METHODS: The study included 62 eyes of
      58 patients divided into three groups using three different IOLs: Crystalens HD
      (Bausch and Lomb, NY, USA), Tek-Clear (Tekia, CA, USA) and SA60AT (Alcon, TX,
      USA) were implanted in 23, 14 and 25 eyes, respectively. Corrected distant visual
      acuity (CDVA), uncorrected and distance corrected near visual acuities (UCNVA and
      DCNVA), near point of accommodation (NPA), spectacle freedom and patient
      satisfaction were assessed six months postoperatively and compared between the
      three groups. RESULTS: After 6 months, all patients showed significant
      improvement in CDVA with no significant difference among the study groups.
      However, UCNVA and DCNVA were significantly better in patients implanted with
      accommodating IOLs. NPA was closest in the Crystalens HD group, followed by Tek
      Clear and monofocal SA60AT (P < 0.001). Patients with accommodating IOLs were
      more likely to become spectacle free and satisfied with their near vision as
      compared to subjects receiving a monofocal IOL. CONCLUSIONS: Accommodating IOLs
      (Crystalens HD and Tek-Clear) effectively reduce the necessity for spectacles
      after cataract surgery.

PMID- 27051481
TI  - Factors Associated with Complications and Postoperative Visual Outcomes of
      Cataract Surgery; a Study of 1,632 Cases.
AB  - PURPOSE: Cataract surgery is the most common intraocular surgery performed all
      over the world and has advanced technically in recent years. As in all surgeries,
      complications are unavoidable. Herein we report factors associated with
      complications and visual outcomes of cataract surgery. METHODS: This
      retrospective cohort study included data of 1,632 cataract surgeries performed
      from 2007 to 2010 which was obtained from the cataract registry of the Malaysian
      National Eye Database. Demographic features, ocular and systemic comorbidites,
      grade of surgeon expertise and duration of surgery, type of anesthesia,
      intraoperative and postoperative complications, and the type of intraocular lens
      were recorded. Best corrected visual acuities were compared before and after the
      operation. RESULTS: Mean patient age was 66.9 years with equal gender
      distribution. The majority of subjects had age related cataracts.
      Phacoemulsification was done faster than other surgeries, especially by
      specialist surgeons. History of prior ocular surgery and operations performed
      under general anesthesia were associated with greater complications.
      Phacoemulsification was associated with less complications and better visual
      outcomes. The age and etiology of cataract did not affect complications. Malays,
      absence of ocular comorbidities, left eyes and eyes operated under local
      anesthesia were more likely to experience more visual improvement. Gender, age,
      cause of cataract, systemic comorbidities and surgeon expertise as well as intra
      and postoperative complications did not affect the visual outcomes. CONCLUSION:
      Phacoemulsification had good visual outcomes in cataract surgery. Duration of
      surgery, expertise of the surgeon and complications did not affect the visual
      outcomes.

PMID- 27051482
TI  - Lens Extraction for Management of Coexisting Cataract and Post-filtering Surgery
      Ocular Hypotony.
AB  - PURPOSE: To evaluate the safety and efficacy of phacoemulsification for
      management of post-filtering ocular hypotony. METHODS: This prospective
      interventional case series study recruited 21 consecutive patients with an
      established diagnosis of ocular hypotony with or without maculopathy. Clear
      corneal incision phacoemulsification was done for all patients. Nineteen cases
      that completed a follow-up of at least 6 months were considered for final
      analysis. RESULTS: Mean baseline intraocular pressure (IOP) was 2.95 +/- 1.43 mm
      Hg, which increased to 8.84 +/- 4.67 mm Hg at 6 months (P < 0.001). Hypotony was
      resolved in 13 cases (68%) at 6 months while 6 cases (32%) showed persistent
      hypotony at this time point. Postoperative IOP change at all follow-up time
      points was not correlated with patient age, time interval between filtering
      surgery and phacoemulsification, baseline IOP, baseline anterior chamber depth
      and IOP on the first postoperative day. Three cases (16%) showed filtering bleb
      failure with dramatic IOP rise around the first postoperative month and required
      glaucoma medication for IOP control. No significant intra- or postoperative
      complications were noted. CONCLUSION: Cataract surgery alone seems promising in
      resolving hypotony in patients with post-filtering ocular hypotony, and can be
      considered as an effective treatment modality before proceeding to more
      complicated procedures.

PMID- 27051483
TI  - Mitomycin-C Application Before versus After Scleral Flap Dissection in
      Trabeculectomy; a Randomized Clinical Trial.
AB  - PURPOSE: To compare trabeculectomy with mitomycin-C (MMC) application before
      versus after scleral flap dissection in terms of corneal endothelial cell loss
      and surgical outcomes. METHODS: In this double blind clinical trial, patients
      were randomized to MMC 0.02% application before (group A) or after (group B)
      scleral flap dissection. The main outcome measure was corneal endothelial cell
      density; secondary outcome measures included IOP, glaucoma medications, success
      rates (IOP <=21 and <=18 mmHg, defined as criterion 1 and 2, respectively) and
      complications. RESULTS: Overall, 99 eyes of 99 subjects including 72 male and 27
      female subjects were operated and followed for at least 6 months. The study
      groups were comparable in terms of baseline variables. Outcomes of surgery were
      similar at six months in terms of IOP (11.8+/-5.8 vs. 11.7+/-5.5 mmHg, P=0.88)
      and number of medications (0.2 +/-0.6 vs 0.1+/-0.4, P=0.45). Overall success was
      comparable at months 1 and 3, but higher in group B at month 6 (82.0% vs. 63.3%,
      P=0.036 for criterion 1 and 78.9% vs. 59.2%, P=0.044 for criterion 2). Hypotony
      was more prevalent in group B (8.0% versus 2.0%) but the difference was not
      significant (P=0.38). Endothelial cell density loss (2.2+/-7.3 vs 0.9+/-6.3%,
      P=0.567) was comparable between the study groups. CONCLUSION: Corneal endothelial
      loss following trabeculectomy was comparable with MMC application before and
      after scleral flap dissection. The sequences were comparable in terms of
      postoperative IOP and glaucoma medications. Overall success rate was higher at
      six months in group B and the rate of hypotony was also higher, although
      insignificantly.

PMID- 27051484
TI  - Hyperopia and Lens Power in an Adult Population: The Shahroud Eye Study.
AB  - PURPOSE: To explore the relationship between lens power and refractive error in
      older adults following age-related hyperopic shifts. METHODS: From the Shahroud
      Eye Cohort Study, subjects aged 55-64 years without clinically significant
      cataracts (with nuclear opacity of grade 0 to 1) were included to maximize the
      proportion of subjects with age-related hyperopic shifts that normally occur
      between 40 to 60 years of age, before interference from the myopic shift due to
      nuclear cataracts. Mean axial length (AL) values, corneal power, anterior chamber
      depth, lens thickness, and lens power were analyzed and compared among three
      refractive groups (myopes, emmetropes, and hyperopes). RESULTS: A total of 1,006
      subjects including 496 (49.63%) male subjects were studied. Corneal power was
      similar in all refractive groups. Hyperopes had + 1.69 diopters higher mean
      spherical equivalent refractive error and - 0.50 mm shorter AL than emmetropes.
      Myopes had 0.67 mm longer AL than emmetropes. Hyperopes had significantly
      increased lens thickness as compared to emmetropes (4.42 vs. 4.39 mm
      respectively). In this adult sample, the hyperopic group had lower lens power
      (+22.29 diopters vs. +22.54 diopters in emmetropes, P = 0.132). Myopes had
      similar lens power as emmetropes. CONCLUSION: Axial length is the principal
      determinant of refractive errors. Lens power may have importance in determining
      hyperopia in adults free of cataract.

PMID- 27051485
TI  - Prevalence of Amblyopia and Refractive Errors Among Primary School Children.
AB  - PURPOSE: To determine the prevalence of amblyopia and refractive errors among 7
      to 12-year-old primary school children in Tehran, Iran. METHODS: This population
      based cross-sectional study included 2,410 randomly selected students. Visual
      acuity was tested using an E-chart on Yang vision tester. Refractive errors were
      measured by photorefractometry and cycloautorefraction. Strabismus was checked
      using cover test. Direct ophthalmoscopy was used to assess the anterior segment,
      lens opacities, red reflex and fundus. Functional amblyopia was defined as best
      corrected visual acuity <=20/40 in one or both eyes with no anatomical problems.
      RESULTS: Amblyopia was present in 2.3% (95% CI: 1.8% to 2.9%) of participants
      with no difference between the genders. Amblyopic subjects were significantly
      younger than non-amblyopic children (P=0.004). Overall, 15.9% of hyperopic and
      5.9% of myopic cases had amblyopia. The prevalence of hyperopia >=+2.00D, myopia
      <=-0.50D, astigmatism >=0.75D, and anisometropia (>=1.00D) was 3.5%, 4.9%, 22.6%,
      and 3.9%, respectively. With increasing age, the prevalence of myopia increased
      (P<0.001), that of hyperopia decreased (P=0.007), but astigmatism showed no
      change. Strabismus was found in 2.3% of cases. Strabismus (OR=17.9) and
      refractive errors, especially anisometropia (OR=12.87) and hyperopia (OR=11.87),
      were important amblyogenic risk factors. CONCLUSION: The high prevalence of
      amblyopia in our subjects in comparison to developed countries reveals the
      necessity of timely and sensitive screening methods. Due to the high prevalence
      of amblyopia among children with refractive errors, particularly high hyperopia
      and anisometropia, provision of glasses should be specifically attended by
      parents and supported by the Ministry of Health and insurance organizations.

PMID- 27051486
TI  - Predictive Value of Pupillary Response to Mydriatic Agents for Diagnosis of
      Retinopathy of Prematurity.
AB  - PURPOSE: To evaluate the feasibility of screening for retinopathy of prematurity
      (ROP) by assessing the pupillary response to mydriatics. METHODS: This
      observational case series included 134 eyes of 67 premature infants with birth
      weight less than 2,000 grams and gestational age less than 33 weeks. A composite
      eye drop composed of phenylephrine 1%, tetracaine and tropicamide 0.5% was
      applied 3 times within 5-minute intervals and pupil diameters were measured. The
      eyes were examined by experienced ROP specialists using an indirect
      ophthalmoscope. Zone and stage of ROP, presence of plus disease and need for
      treatment were recorded. The relationship between the pupillary response to
      mydriatics, and presence and severity of ROP was evaluated. Logistic regression
      was used for statistical analysis. RESULTS: According to receiver operating
      characteristic (ROC) curve analysis, final pupil diameter after mydriatic
      administration was found the most accurate factor among other factors to
      recognize ROP zone I from zones II and III (Area under ROC: 0.92 [95%CI: 0.85
      0.98]). The best cutoff value for final pupil diameter was 5.6 mm, because it
      could differentiate involvement of zone I from zones II and III with sensitivity
      of 80% and specificity of 100%. CONCLUSION: Response of the pupil to mydriatic
      eye drops may be useful as a less invasive method for rough estimation of ROP in
      high risk babies who need emergent attention; however, it cannot be considered as
      a screening test due to its low sensitivity.

PMID- 27051487
TI  - Incidence and Risk Factors for Retinopathy of Prematurity in North of Iran.
AB  - PURPOSE: To report the incidence and risk factors for retinopathy of prematurity
      (ROP) among preterm infants referred to Amiralmomenin Eye Hospital, Rasht, Iran.
      METHODS: This cross-sectional retrospective study included all preterm infants
      with birth weight <=2500 g and/or gestational age <=36 weeks who had been
      referred to our facility for ROP screening over a five year period from September
      2005 to September 2010. Possible risk factors and findings related to eye
      examinations were extracted and analyzed. RESULTS: Among 310 infants, ROP was
      diagnosed in 64 (20.6%) of referred preterm infants (95% CI: 17.7%-23.5%); these
      included stage I in 48%, stage 2 in 29%, and stage 3 or higher disease in 23% of
      subjects. Mean gestational age (GA) and birth weight (BW) in the ROP-affected
      infants was 30.18 +/- 2.28 weeks and 1,422.8 +/- 420.8 g, respectively. Low BW,
      low GA, oxygen therapy, phototherapy, blood transfusion and apnea were risk
      factors for ROP. After logistic regression analysis, only low GA and low BW were
      independently associated with the condition. CONCLUSION: ROP is a relatively
      common finding in preterm infants of Guilan Province in the North of Iran. Low BW
      and low GA were significant risk factors for the disease.

PMID- 27051488
TI  - Quantity and Quality of Vision Using Tinted Filters in Patients with Low Vision
      Due to Diabetic Retinopathy.
AB  - PURPOSE: To investigate the effect of tinted filters on visual acuity (VA),
      contrast sensitivity and patient satisfaction in diabetic retinopathy associated
      with low vision. METHODS: In a prospective study, 51 patients with diabetic
      retinopathy and low vision were assessed. We chose a simple random sampling
      method and used the patient's files for data collection. LogMAR notations were
      applied for assessing VA and a contrast sensitivity chart (CSV-1000) was employed
      for measuring contrast sensitivity. First, measurements were performed without
      tinted filters and then using them. Appropriate lenses were given to the patients
      for 2 days, and they were questioned about their satisfaction using them in
      different places. RESULTS: A total of 20 male and 31 female patients with mean
      age of 57.3 years participated in the study. With a 527 +/- 10 nm filter, mean VA
      improved significantly (P <= 0.05). Using the 527 +/- 10 nm and 511 +/- 10 nm
      filters, mean contrast sensitivity was improved significantly at 3 and 6
      cycles/degree frequencies (P < 0.05). The effect of other filters on VA and
      contrast sensitivity was not significant. Patient satisfaction rate was generally
      high. CONCLUSION: Tinted filters are able to rehabilitate low-vision patients due
      to diabetic retinopathy. The 527 +/- 10 and 511 +/- 10 nm wavelength filters
      improved contrast sensitivity and the 527 +/- 10 nm filter improved VA to some
      extent. Further investigations are recommended to assess the effect of these
      filters in patients with other causes of low-vision.

PMID- 27051489
TI  - Psychophysical Evidence for Impaired Magno, Parvo, and Konio-cellular Pathways in
      Dyslexic Children.
AB  - PURPOSE: Dyslexia is one of the most common learning disabilities affecting
      millions of people worldwide. Although exact causes of dyslexia are not well
      known, a deficit in the magnocellular pathway may play a role. We examined
      possible deficiency of magnocellular, as compared to parvocellular and
      koniocellular pathway function by measuring luminance and color perception.
      METHODS: Visual stimuli consisted of a series of natural images, divided into
      layers of luminance, red-green and blue-yellow, which probed magnocellular,
      parvocellular, and koniocellular pathways, respectively. Thirteen children with
      dyslexia and 13 sex- and age- matched controls performed three psychophysical
      tasks. In the first task, subjects were instructed to match the contrast of
      luminance (magno) and red-green (parvo) images to that of the blue-yellow (konio)
      images. In the second task, subjects detected the isoluminant point of red-green
      images to probe parvocellular pathway. In the third task, temporal processing was
      assessed by measuring reaction time and percentage of correct responses in an
      identification task using four categories of images, activating all three
      pathways. RESULTS: The dyslexic group had significantly elevated luminance and
      color contrast thresholds and higher isoluminant point ratio in comparison to the
      control group. Furthermore, they had significantly less correct responses than
      the control group for the blue-yellow images. CONCLUSION: We may suggest that
      dyslexic subjects might suffer from both magnocellular and parvocellular
      deficits. Moreover, our results show partial impairment of the koniocellular
      pathway. Thus, dyslexia might be associated with deficits in all three visual
      pathways.

PMID- 27051490
TI  - Do UV-blocking Soft Contact Lenses Meet ANSI Z80.20 Criteria for UV
      Transmittance?
AB  - PURPOSE: To compare ultraviolet (UV) ray transmission in four UV-blocking soft
      contact lenses with Z80.20 standards set by the American National Standards
      Institute (ANSI). METHODS: Four soft contact lenses including Acuvue Oasys
      (Johnson & Johnson, Ireland), Acuvue 2 (Johnson & Johnson, Ireland), Zeiss
      CONTACT Day 30 (Zeiss, Germany), and Sauflon 55 UV (Sauflon, UK) were evaluated
      for UV transmission. One-way ANOVA testing was performed to compare mean values
      of UVA and UVB transmission for the contact lenses. RESULTS: Acuvue Oasys, Acuvue
      2, Zeiss CONTACT Day 30 and Sauflon 55 UV showed UV-B transmittance values of
      0.24%, 1.46%, 10.37%, and 2.52%, respectively. Corresponding values for UV-A
      transmittance were 20.81%, 33.49%, 44.03% and 42.53%, respectively. One-way ANOVA
      showed a statistically significant difference among the tested contact lenses in
      terms of UV-B (P < 0.001) and UV-A (P < 0.001) transmission. CONCLUSION: Acuvue
      Oasys met the ANSI criteria for UV transmission and may thus be a good choice for
      eye and vision care specialists and contact lens wearers seeking UV protection.

PMID- 27051492
TI  - Descemet's Stripping Automated Endothelial Keratoplasty Tissue Insertion Devices.
AB  - This review study provides information regarding the construction, design, and
      use of six commercially available endothelial allograft insertion devices applied
      for Descemet's stripping automated endothelial keratoplasty (DSAEK). We also
      highlight issues being faced in DSAEK and discuss the methods through which
      medical devices such as corneal inserters may alleviate these issues. Inserter
      selection is of high importance in the DSAEK procedure since overcoming the
      learning curve associated with the use of an insertion device is a time and
      energy consuming process. In the present review, allograft insertion devices were
      compared in terms of design, construction material, insertion technique,
      dimensions, incision requirements and endothelial cell loss to show their
      relative merits and capabilities based on available data in the literature.
      Moreover, the advantages/disadvantages of various insertion devices used for
      allograft insertion in DSAEK are reviewed and compared. The information presented
      in this review can be utilized for better selection of an insertion device for
      DSAEK. 

PMID- 27051491
TI  - Customized Clinical Practice Guidelines for Management of Adult Cataract in Iran.
AB  - PURPOSE: To customize clinical practice guidelines (CPGs) for cataract management
      in the Iranian population. METHODS: First, four CPGs (American Academy of
      Ophthalmology 2006 and 2011, Royal College of Ophthalmologists 2010, and Canadian
      Ophthalmological Society 2008) were selected from a number of available CPGs in
      the literature for cataract management. All recommendations of these guidelines,
      together with their references, were studied. Each recommendation was summarized
      in 4 tables. The first table showed the recommendation itself in clinical
      question components format along with its level of evidence. The second table
      contained structured abstracts of supporting articles related to the clinical
      question with their levels of evidence. The third table included the customized
      recommendation of the internal group respecting its clinical advantage, cost, and
      complications. In the fourth table, the internal group their recommendations from
      1 to 9 based on the customizing capability of the recommendation (applicability,
      acceptability, external validity). Finally, customized recommendations were sent
      one month prior to a consensus session to faculty members of all universities
      across the country asking for their comments on recommendations. RESULTS: The
      agreed recommendations were accepted as conclusive while those with no agreement
      were discussed at the consensus session. Finally, all customized recommendations
      were codified as 80 recommendations along with their sources and levels of
      evidence for the Iranian population. CONCLUSION: Customization of CPGs for
      management of adult cataract for the Iranian population seems to be useful for
      standardization of referral, diagnosis and treatment of patients.

PMID- 27051493
TI  - Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual
      Prognosis.
AB  - Pars planitis is an idiopathic chronic intermediate uveitis which predominantly
      affects children and adolescents, and accounts for 5-26.7% of pediatric uveitis.
      Although an autoimmune process with a genetic predisposition has been suggested,
      its etiology still remains unknown. The most common presenting symptoms are
      floaters and blurred vision. Diffuse vitreous cells, haze, snowballs and
      snowbanks are typical findings of pars planitis. Peripheral retinal vasculitis,
      optic disc edema and anterior segment inflammation are other well-known findings.
      Although pars planitis is known to be a benign form of uveitis in most cases, it
      may become a potentially blinding disease due to complications including
      cataract, cystoid macular edema, vitreous opacities and optic disc edema. Cystoid
      macular edema is the most common cause of visual morbidity. Band keratopathy,
      epiretinal membrane formation, vitreous condensation, neovascularizations,
      vitreous hemorrhage, retinal detachment, cyclitic membranes, glaucoma and
      amblyopia may develop as a consequence of the chronic course of the disease.
      Exclusion of infectious and non-infectious causes which may present with
      intermediate uveitis is of utmost importance before starting treatment. Treatment
      of pars planitis has been a controversial issue. There is no consensus
      specifically for treatment of cases with minimal inflammation and relatively good
      visual acuity. However, current experience shows that pars planitis may cause
      severe inflammation and needs an aggressive treatment. A stepladder approach
      including corticosteroids, immunosupressive agents, anti-tumor necrosis factor
      alpha and pars plana vitrectomy and/or laser photocoagulation is the most
      commonly used method for treatment of pars planitis. Adequate control of
      inflammation and prompt detection of associated complications are crucial in
      order to improve the overall prognosis of the disease. 

PMID- 27051494
TI  - Allergic Conjunctival Granuloma Presenting the Splendore-Hoeppli Phenomenon;
      Report of Two Cases and Review of Literature.
AB  - To report two cases of bilateral conjunctival granuloma with histopathological
      features of the Splendore-Hoeppli phenomenon and review of the literature. Two
      female patients, one with a history of pulmonary eosinophilic infiltration and
      another with a history of vernal keratoconjunctivitis, presented with bilateral
      cream to yellow colored nodules in the superior bulbar conjunctiva.
      Histopathologic examination revealed characteristic features of the Splendore
      Hoeppli phenomenon manifesting as zones of amorphous eosinophilic material
      surrounded by aggregations of epithelioid histiocytes, giant cells, eosinophils
      and lymphoplasmacytic infiltrates. No evidence of infectious organisms was found.
      Our report adds to non-infectious cases of conjunctival Splendore-Hoeppli
      phenomenon. Previous history of allergic disorders may have contributed to the
      occurrence of this entity. 

PMID- 27051495
TI  - Intravitreal Bevacizumab for Management of Choroidal Osteoma without Choroidal
      Neovascularization.
AB  - To report a patient with juxtapapillary choroidal osteoma (CO) with serous
      retinal detachment (SRD) not associated with choroidal neovascularization (CNV)
      who was successfully treated with a single intravitreal injection of bevacizumab.
      A 20-year-old woman presented with decreased vision in her right eye.
      Ultrasonography, fundus autofluorescence, fluorescein angiography (FA) and
      optical coherence tomography (OCT) were performed. She was diagnosed with
      juxtapapillary CO with SRD in the absence of CNV. The treatment involved a single
      intravitreal injection of bevacizumab. Visual acuity (VA) was 20/100 pre
      injection which was dramatically improved to 20/20 one week after the injection
      without any additional treatment. Fundus examination and OCT one week after the
      injection revealed complete absorption of the subretinal fluid (SRF) in the
      macula. Eighteen months after the injection, vision remained stable and she did
      not show re-accumulation of SRF in her right eye. Intravitreal injection of
      bevacizumab may be effective in managing CO associated with SRF without CNV. 

PMID- 27051496
TI  - Unilateral Ischemic Maculopathy Associated with Cytomegalovirus Retinitis in
      Patients with AIDS: Optical Coherence Tomography Findings.
AB  - To describe the clinical and optical coherence tomography (OCT) characteristics
      of ischemic maculopathy in two patients with acquired immunodeficiency syndrome
      (AIDS). Two patients with AIDS and cytomegalovirus (CMV) retinitis developed
      ischemic maculopathy. Both patients presented with central visual loss and active
      granular CMV retinitis. The presence of opacification of the superficial retina
      in the macular area and intraretinal edema suggested the diagnosis. Fluorescein
      angiography changes were similar in the two cases with enlargement of the foveal
      avascular zone and late staining of juxtafoveal vessels. OCT changes were
      suggestive of retinal ischemia: Increased reflectivity from the inner retinal
      layer and decreased backscattering from the retinal photoreceptors due to fluid
      and retinal edema. Ischemic maculopathy may cause a severe and permanent decrease
      in vision in AIDS patients. Fluorescein angiography and OCT should be considered
      in any patient with AIDS and unexplained visual loss. The mechanism of ischemic
      maculopathy may be multifactorial. 

PMID- 27051497
TI  - Demonstration of Retinal Micro-emboli in a Case of Malaria Retinopathy by Fundus
      Fluorescein Angiography.

PMID- 27051498
TI  - Multiple Retinal Vein Occlusions Associated with Anti-thrombin III Deficiency.

PMID- 27051499
TI  - Combined Epiretinal and Internal Limiting Membrane Peeling Facilitated by High
      Dilution Indocyanine Green Negative Staining.
AB  - We describe the utilization of indocyanine green (ICG) dye to facilitate
      combined/en bloc removal of epiretinal membranes (ERM) along with internal
      limiting membranes (ILM). The method utilizes a highly diluted preparation of ICG
      in dextrose water solvent (D5W). Elimination of fluid air exchange step
      facilitating staining in the fluid phase and low intensity lighting help minimize
      potential ICG toxicity. The technique demonstrates how ICG facilitates negative
      staining of ERMs and how ILM peeling concomitantly can allow complete and
      efficient ERM removal minimizing surgical time and the necessity for dual or
      sequential staining. 

PMID- 27051500
TI  - Single Session, Intra-observer Repeatability of an Advanced New Generation
      Hartmann-Shack Aberrometer in Refractive Surgery Candidates.

PMID- 27051501
TI  - A New Look at Glaucoma.

PMID- 27051502
TI  - Author's Reply.

PMID- 27051503
TI  - Vitreous Haemorrhage in Children.

PMID- 27051504
TI  - Authors' Reply.

PMID- 27051505
TI  - Sex impacts Th1 cells, Tregs, and DCs in both intestinal and systemic immunity in
      a mouse strain and location-dependent manner.
AB  - BACKGROUND: Males and females have a different predisposition for the development
      of intestinal disorders, like inflammatory bowel disease (IBD). We hypothesized
      that sex specific differences in intestinal immune responses may underlie this
      bias. To test this hypothesis, we studied sex differences in immune cell
      populations in the Peyer's patches (PP). For comparison with systemic immunity,
      we studied spleen cells. METHODS: Two mouse strains with different susceptibility
      for developing colitis (BALB/c and C57Bl/6) were used. Using flow cytometry, we
      measured the percentage of T cells, Th1, Th17, and Treg cells in the PP and
      spleen. In addition, we measured the percentages of NK cells, macrophages,
      myeloid, and lymphoid dendritic cells (DCs) and their expression of CD80 and
      CD103. Moreover, we measured percentages of monocyte subsets in the peripheral
      circulation. Results were tested using two-way ANOVA, p < 0.05. RESULTS: Males
      had a lower percentage of T cells in both PP and spleen (PP BALB/c 22.1 %, B6
      13.6 %; spleen BALB/c 4.7 %, B6 19.9 %) but a higher percentage of Th1 cell in
      both tissues (PP BALB/c 350 %, B6 109.5 %; spleen BALB/c 48.7 %, B6 41.9 %) than
      females. They also had a higher percentage of Tregs in the spleen than females
      (BALB/c 20.5 %, B6 4.5 %). Furthermore, males had a higher percentage of CD80(+)
      DCs in both the PP and spleen (lymphoid DCs in PP BALB/c 104.7 %, B6 29.6 %;
      spleen BALB/c 72.2 %, B6 44.2 %; myeloid DCs in PP BALB/c 80.5 %, B6 93.3 %;
      spleen BALB/c 88.5 %, B6 50.8 %) and a higher percentage of lymphoid CD103(+) DCs
      in the spleen than females (BALB/c 41.5 %, B6 28.3 %). The percentage of NK cells
      was decreased in the spleen (BALB/c 12.5 %, B6 25.1 %) but increased in the PP
      (BALB/c 75.7 %, B6 78.6 %) of males as compared with females. Strain differences
      were also found in the PP; BALB/c mice had a higher percentage of T cells (males
      58.1 %, females 75.5 %), a higher Th/Tc ratio (males 81.0 %, females 134.2 %),
      less FoxP3(+)CD25(-) T cells (males 14.6 %, females 30.0 %), more DCs (males 14.8
      %, females 15.7 %) and macrophages (males 67.9 %, females 141.2 %), and more NK
      cells (males 160 %, females164.3 %) than BALB/c mice. CONCLUSIONS: In this study,
      we show sex differences in intestinal and peripheral immune populations. These
      differences may underlie sex differences in intestinal disorders like IBD, and
      this information may be an important knowledge for the treatment of intestinal
      related diseases.

PMID- 27051506
TI  - Requirements for multi-level systems pharmacology models to reach end-usage: the
      case of type 2 diabetes.
AB  - We are currently in the middle of a major shift in biomedical research:
      unprecedented and rapidly growing amounts of data may be obtained today, from in
      vitro, in vivo and clinical studies, at molecular, physiological and clinical
      levels. To make use of these large-scale, multi-level datasets, corresponding
      multi-level mathematical models are needed, i.e. models that simultaneously
      capture multiple layers of the biological, physiological and disease-level
      organization (also referred to as quantitative systems pharmacology-QSP-models).
      However, today's multi-level models are not yet embedded in end-usage
      applications, neither in drug research and development nor in the clinic. Given
      the expectations and claims made historically, this seemingly slow adoption may
      seem surprising. Therefore, we herein consider a specific example-type 2 diabetes
      and critically review the current status and identify key remaining steps for
      these models to become mainstream in the future. This overview reveals how,
      today, we may use models to ask scientific questions concerning, e.g., the
      cellular origin of insulin resistance, and how this translates to the whole-body
      level and short-term meal responses. However, before these multi-level models can
      become truly useful, they need to be linked with the capabilities of other
      important existing models, in order to make them 'personalized' (e.g. specific to
      certain patient phenotypes) and capable of describing long-term disease
      progression. To be useful in drug development, it is also critical that the
      developed models and their underlying data and assumptions are easily accessible.
      For clinical end-usage, in addition, model links to decision-support systems
      combined with the engagement of other disciplines are needed to create user
      friendly and cost-efficient software packages. 

PMID- 27051507
TI  - Improving the physiological realism of experimental models.
AB  - The Virtual Physiological Human (VPH) project aims to develop integrative,
      explanatory and predictive computational models (C-Models) as numerical
      investigational tools to study disease, identify and design effective therapies
      and provide an in silico platform for drug screening. Ultimately, these models
      rely on the analysis and integration of experimental data. As such, the success
      of VPH depends on the availability of physiologically realistic experimental
      models (E-Models) of human organ function that can be parametrized to test the
      numerical models. Here, the current state of suitable E-models, ranging from in
      vitro non-human cell organelles to in vivo human organ systems, is discussed.
      Specifically, challenges and recent progress in improving the physiological
      realism of E-models that may benefit the VPH project are highlighted and
      discussed using examples from the field of research on cardiovascular disease,
      musculoskeletal disorders, diabetes and Parkinson's disease. 

PMID- 27051508
TI  - Understanding the physiology of the ageing individual: computational modelling of
      changes in metabolism and endurance.
AB  - Ageing and lifespan are strongly affected by metabolism. The maximal possible
      uptake of oxygen is not only a good predictor of performance in endurance sports,
      but also of life expectancy. Figuratively speaking, healthy ageing is a
      competitive sport. Although the root cause of ageing is damage to macromolecules,
      it is the balance with repair processes that is decisive. Reduced or intermittent
      nutrition, hormones and intracellular signalling pathways that regulate
      metabolism have strong effects on ageing. Homeostatic regulatory processes tend
      to keep the environment of the cells within relatively narrow bounds. On the
      other hand, the body is constantly adapting to physical activity and food
      consumption. Spontaneous fluctuations in heart rate and other processes indicate
      youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age.
      We are now in a position to develop computational models of human metabolism and
      the dynamics of heart rhythm and oxygen transport that will advance our
      understanding of ageing. Computational modelling of the connections between
      dietary restriction, metabolism and protein turnover may increase insight into
      homeostasis of the proteins in our body. In this way, the computational
      reconstruction of human physiological processes, the Physiome, can help prevent
      frailty and age-related disease. 

PMID- 27051510
TI  - Multiscale musculoskeletal modelling, data-model fusion and electromyography
      informed modelling.
AB  - This paper proposes methods and technologies that advance the state of the art
      for modelling the musculoskeletal system across the spatial and temporal scales;
      and storing these using efficient ontologies and tools. We present population
      based modelling as an efficient method to rapidly generate individual morphology
      from only a few measurements and to learn from the ever-increasing supply of
      imaging data available. We present multiscale methods for continuum muscle and
      bone models; and efficient mechanostatistical methods, both continuum and
      particle-based, to bridge the scales. Finally, we examine both the importance
      that muscles play in bone remodelling stimuli and the latest muscle force
      prediction methods that use electromyography-assisted modelling techniques to
      compute musculoskeletal forces that best reflect the underlying neuromuscular
      activity. Our proposal is that, in order to have a clinically relevant virtual
      physiological human, (i) bone and muscle mechanics must be considered together;
      (ii) models should be trained on population data to permit rapid generation and
      use underlying principal modes that describe both muscle patterns and morphology;
      and (iii) these tools need to be available in an open-source repository so that
      the scientific community may use, personalize and contribute to the database of
      models. 

PMID- 27051509
TI  - Multiphysics and multiscale modelling, data-model fusion and integration of organ
      physiology in the clinic: ventricular cardiac mechanics.
AB  - With heart and cardiovascular diseases continually challenging healthcare systems
      worldwide, translating basic research on cardiac (patho)physiology into clinical
      care is essential. Exacerbating this already extensive challenge is the
      complexity of the heart, relying on its hierarchical structure and function to
      maintain cardiovascular flow. Computational modelling has been proposed and
      actively pursued as a tool for accelerating research and translation. Allowing
      exploration of the relationships between physics, multiscale mechanisms and
      function, computational modelling provides a platform for improving our
      understanding of the heart. Further integration of experimental and clinical data
      through data assimilation and parameter estimation techniques is bringing
      computational models closer to use in routine clinical practice. This article
      reviews developments in computational cardiac modelling and how their integration
      with medical imaging data is providing new pathways for translational cardiac
      modelling. 

PMID- 27051511
TI  - Participatory medicine: model based tools for engaging and empowering the
      individual.
AB  - The long-term goal of the Virtual Physiological Human and Digital Patient
      projects is to run 'simulations' of health and disease processes on the virtual
      or 'digital' patient, and use the results to make predictions about real health
      and determine the best treatment specifically for an individual. This is termed
      'personalized medicine', and is intended to be the future of healthcare. How will
      people interact and engage with their virtual selves, and how can virtual models
      be used to motivate people to actively participate in their own healthcare? We
      discuss these questions, and describe our current efforts to integrate and
      realistically embody psychobiological models of face-to-face interaction to
      enliven and increase engagement of virtual humans in healthcare. Overall, this
      paper highlights the need for attention to the design of human-machine interfaces
      to address patient engagement in healthcare. 

PMID- 27051513
TI  - A physiome interoperability roadmap for personalized drug development.
AB  - The goal of developing therapies and dosage regimes for characterized subgroups
      of the general population can be facilitated by the use of simulation models able
      to incorporate information about inter-individual variability in drug disposition
      (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such
      observed variability can have multiple causes at various scales, ranging from
      gross anatomical differences to differences in genome sequence. Relevant data for
      many of these aspects, particularly related to molecular assays (known as '
      omics'), are available in online resources, but identification and assignment to
      appropriate model variables and parameters is a significant bottleneck in the
      model development process. Through its efforts to standardize annotation with
      consequent increase in data usability, the human physiome project has a vital
      role in improving productivity in model development and, thus, the development of
      personalized therapy regimes. Here, we review the current status of personalized
      medicine in clinical practice, outline some of the challenges that must be
      overcome in order to expand its applicability, and discuss the relevance of
      personalized medicine to the more widespread challenges being faced in drug
      discovery and development. We then review some of (i) the key data resources
      available for use in model development and (ii) the potential areas where
      advances made within the physiome modelling community could contribute to
      physiologically based pharmacokinetic and physiologically based
      pharmacokinetic/pharmacodynamic modelling in support of personalized drug
      development. We conclude by proposing a roadmap to further guide the physiome
      community in its on-going efforts to improve data usability, and integration with
      modelling efforts in the support of personalized medicine development. 

PMID- 27051512
TI  - Mathematics in modern immunology.
AB  - Mathematical and statistical methods enable multidisciplinary approaches that
      catalyse discovery. Together with experimental methods, they identify key
      hypotheses, define measurable observables and reconcile disparate results. We
      collect a representative sample of studies in T-cell biology that illustrate the
      benefits of modelling-experimental collaborations and that have proven valuable
      or even groundbreaking. We conclude that it is possible to find excellent
      examples of synergy between mathematical modelling and experiment in immunology,
      which have brought significant insight that would not be available without these
      collaborations, but that much remains to be discovered. 

PMID- 27051514
TI  - Requirements for the formal representation of pathophysiology mechanisms by
      clinicians.
AB  - Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical
      practice. If quantitative methods, predicting patient-specific behaviour of these
      pathophysiology mechanisms, are to be brought to bear on clinical decision
      making, the Human Physiome community and Clinical community must share a common
      computational blueprint for pathophysiology mechanisms. A number of obstacles
      stand in the way of this sharing-not least the technical and operational
      challenges that must be overcome to ensure that (i) the explicit biological
      meanings of the Physiome's quantitative methods to represent mechanisms are open
      to articulation, verification and study by clinicians, and that (ii) clinicians
      are given the tools and training to explicitly express disease manifestations in
      direct contribution to modelling. To this end, the Physiome and Clinical
      communities must co-develop a common computational toolkit, based on this
      blueprint, to bridge the representation of knowledge of pathophysiology
      mechanisms (a) that is implicitly depicted in electronic health records and the
      literature, with (b) that found in mathematical models explicitly describing
      mechanisms. In particular, this paper makes use of a step-wise description of a
      specific disease mechanism as a means to elicit the requirements of representing
      pathophysiological meaning explicitly. The computational blueprint developed from
      these requirements addresses the Clinical community goals to (i) organize and
      manage healthcare resources in terms of relevant disease-related knowledge of
      mechanisms and (ii) train the next generation of physicians in the application of
      quantitative methods relevant to their research and practice. 

PMID- 27051515
TI  - The Human Physiome: how standards, software and innovative service
      infrastructures are providing the building blocks to make it achievable.
AB  - Reconstructing and understanding the Human Physiome virtually is a complex
      mathematical problem, and a highly demanding computational challenge.
      Mathematical models spanning from the molecular level through to whole
      populations of individuals must be integrated, then personalized. This requires
      interoperability with multiple disparate and geographically separated data
      sources, and myriad computational software tools. Extracting and producing
      knowledge from such sources, even when the databases and software are readily
      available, is a challenging task. Despite the difficulties, researchers must
      frequently perform these tasks so that available knowledge can be continually
      integrated into the common framework required to realize the Human Physiome.
      Software and infrastructures that support the communities that generate these,
      together with their underlying standards to format, describe and interlink the
      corresponding data and computer models, are pivotal to the Human Physiome being
      realized. They provide the foundations for integrating, exchanging and re-using
      data and models efficiently, and correctly, while also supporting the
      dissemination of growing knowledge in these forms. In this paper, we explore the
      standards, software tooling, repositories and infrastructures that support this
      work, and detail what makes them vital to realizing the Human Physiome. 

PMID- 27051516
TI  - In silico regenerative medicine: how computational tools allow regulatory and
      financial challenges to be addressed in a volatile market.
AB  - The cell therapy market is a highly volatile one, due to the use of disruptive
      technologies, the current economic situation and the small size of the market. In
      such a market, companies as well as academic research institutes are in need of
      tools to advance their understanding and, at the same time, reduce their R&D
      costs, increase product quality and productivity, and reduce the time to market.
      An additional difficulty is the regulatory path that needs to be followed, which
      is challenging in the case of cell-based therapeutic products and should rely on
      the implementation of quality by design (QbD) principles. In silico modelling is
      a tool that allows the above-mentioned challenges to be addressed in the field of
      regenerative medicine. This review discusses such in silico models and focuses
      more specifically on the bioprocess. Three (clusters of) examples related to this
      subject are discussed. The first example comes from the pharmaceutical
      engineering field where QbD principles and their implementation through the use
      of in silico models are both a regulatory and economic necessity. The second
      example is related to the production of red blood cells. The described in silico
      model is mainly used to investigate the manufacturing process of the cell
      therapeutic product, and pays special attention to the economic viability of the
      process. Finally, we describe the set-up of a model capturing essential events in
      the development of a tissue-engineered combination product in the context of bone
      tissue engineering. For each of the examples, a short introduction to some
      economic aspects is given, followed by a description of the in silico tool or
      tools that have been developed to allow the implementation of QbD principles and
      optimal design. 

PMID- 27051517
TI  - Vaccine hesitancy as self-determination: an Israeli perspective.
AB  - Vaccine hesitancy can be portrayed as a broad spectrum of phenomena, ranging from
      a genuine call for help to complete defiance of authorities. The emphasis here is
      made on mid-spectrum hesitancy; hesitancy as an act of personal exploration and
      deliberation whether to get vaccinated or not. This form of vaccine hesitancy can
      be identified in the attitude of the Israeli public towards routine childhood
      vaccination programs, seasonal flu vaccination, newly introduced vaccines, such
      as human papilloma virus vaccine, as well as towards the emergency vaccination
      programs against poliovirus and H1N1 pandemic influenza. Vaccine hesitancy in
      Israel appears to be a process where individuals exercise self-determination and
      self-empowerment and make their own decisions based on assessment, reflection,
      choosing between various options and dealing with considerable complexities.
      Addressing this form of vaccine hesitancy could be challenging, but ultimately
      fruitful. This would require change of attitudes on the part of policymakers. The
      first steps should involve the realization that deliberative hesitancy is here to
      stay, and that hesitant individuals should be respected. This could pave the way
      for designing appropriate intervention strategies for convincing the hesitant
      public about the advantages of vaccination. 

PMID- 27051518
TI  - Triclosan promotes epicutaneous sensitization to peanut in mice.
AB  - BACKGROUND: Peanut allergy is increasing in prevalence due to unknown factors. A
      growing body of clinical evidence suggests sensitization to peanut occurs through
      the skin, supported by findings in mouse models. There is a need to identify
      environmental factors that promote epicutaneous sensitization to peanut.
      Triclosan is an antimicrobial found in household products that has been
      associated with food sensitization in humans. We tested the impact of triclosan
      on epicutaneous sensitization to peanut, as well as the milk allergen alpha
      lactalbumin (ALA). RESULTS: We observed that topical triclosan promoted
      epicutaneous sensitization to both peanut and ALA, and promoted anaphylaxis to
      peanut. CONCLUSIONS: Our results demonstrate that the mouse model of epicutaneous
      sensitization to foods is effective for demonstrating the clinically significant
      impact of environmental factors such as triclosan on food allergy.

PMID- 27051519
TI  - Ultrasound transducer disinfection in emergency medicine practice.
AB  - BACKGROUND: External ultrasound transducer disinfection is common practice in
      medicine. Unfortunately, clinically significant organisms, such as methicillin
      resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella
      pneumonia spread throughout healthcare facilities via direct contact despite
      disinfection protocols. Ultrasound transducers and coupling gel provide potential
      vectors for pathogen transmission, especially in immunocompromised and high-risk
      patient populations. Our objective was to conduct a survey to investigate the
      variety of cleaning solutions or sanitary wipes used and evaluate current
      standard practice for transducer disinfection across emergency medicine training
      programs in the United States. FINDINGS: Eighty-three academic emergency medicine
      programs participated in this study. Eighty-seven percent (95 % CI 80-94 %) of
      responding programs do not have a mandated protocol or standard contact time for
      transducer disinfection. Ninety percent (95 % CI 84-96 %) of institutions use
      disinfectant solution or disinfectant wipes, as the standard of practice, to
      cleanse ultrasound transducers after every use. CONCLUSIONS: Currently, there is
      a great deal of variability with regard to non-endocavitary transducer
      disinfection protocols that seems to stem from the vast number of disinfectant
      products and ultrasound manufacturer disparate recommendations. In order to
      mitigate risk to patients and reduce health care costs linked to nosocomial
      infections; healthcare providers, ultrasound companies, and disinfectant
      manufacturers must develop a universal use disinfectant and a standard protocol
      for ultrasound device disinfection for noncritical device disinfection in the
      emergency department.

PMID- 27051520
TI  - Assessing heating distribution by therapeutic ultrasound on bone phantoms and in
      vitro human samples using infrared thermography.
AB  - BACKGROUND: Bioheat models have been proposed to predict heat distribution in
      multilayered biological tissues after therapeutic ultrasound (TUS) stimulation.
      However, evidence on its therapeutic benefit is still controversial for many
      clinical conditions. The aim of this study was to evaluate and to compare the TUS
      heating distribution on commercially available bone phantoms and in vitro femur
      and tibia human samples, at 1 MHz and several ultrasonic pulse regimens, by means
      of a thermographic image processing technique. METHODS: An infrared camera was
      used to capture an image after each 5-min 1-MHz TUS stimulation on bone phantoms,
      as well as in vitro femur and tibia samples (N = 10). An intensity-based
      processing algorithm was applied to estimate temperature distribution. Sections
      of five femurs in the coronal plane were also used for the evaluation of heat
      distribution inside the medullar canal. RESULTS: Temperature increased up to 8.2
      and 9.8  degrees C for the femur and tibia, respectively. Moreover, the
      temperature increased up to 10.8  degrees C inside the medullar canal. Although
      temperature distributions inside the region of interest (ROI) were significantly
      different (p < 0.001), the average and standard deviation values for bone
      phantoms were more similar to the femur than to the tibia samples. Pulsed
      regimens caused lower increments in temperature than continuous sonication, as
      expected. CONCLUSIONS: Commercially available bone phantoms could be used in
      research focusing on thermal effects of ultrasound. Small differences in mean and
      standard deviation temperatures were observed between bone samples and phantoms.
      Temperature can reach more than 10  degrees C inside the medullar canal on a
      fixed probe position which may lead to severe cellular damage.

PMID- 27051521
TI  - Ultrastructural localization and distribution of Nardilysin in mammalian male
      germ cells.
AB  - BACKGROUND: NRD convertase, also termed Nardilysin, is a Zn(++)
      metalloendopeptidase that specifically cleaves the N-terminus of arginine and
      lysine residues into dibasic moieties. Although this enzyme was found located
      within the testis, its function in male reproduction is largely unknown. In
      addition, the precise distribution of this enzyme within germ cells remains to be
      determined. METHODS: To answer these questions, we developed an immuno-gold
      electron microscopy analysis to detect Nardilysin at ultrastructural level in
      mice. In addition, we performed a quantitative analysis of these gold particles
      to statistically estimate the distribution of Nardilysin in the different
      subcellular compartments of differentiating late spermatids/spermatozoa. RESULTS:
      Expression of Nardilysin in wild-type mice was restricted to germ cells and
      markedly increased during the last steps of spermiogenesis. In elongated
      spermatids, we found the enzyme mainly localized in the cytoplasm, more precisely
      associated with two microtubular structures, the manchette and the axoneme. No
      labelling was detected over the membranous organelles of the spermatids. To test
      whether this localization is dependent of the functional microtubules
      organization of the flagella, we analysed the localization into a specific mouse
      mutant ebo/ebo (ebouriffe) known to be sterile due to an impairment of the final
      organization of the flagellum. In the ebo/ebo, the enzyme was still localized
      over the microtubules of the axoneme and over the isolated cytoplasmic
      microtubules doublets. Quantification of gold particles in wild-type and mutant
      flagella revealed the specific association of the enzyme within the microtubular
      area of the axoneme. CONCLUSIONS: The strong and specific accumulation of
      Nardilysin in the manchette and axoneme suggests that the enzyme probably
      contributes either to the establishment of these specific microtubular structures
      and/or to their functional properties.

PMID- 27051522
TI  - Trends in popularity of some morphological traits of purebred dogs in Australia.
AB  - BACKGROUND: The morphology of dogs can provide information about their
      predisposition to some disorders. For example, larger breeds are predisposed to
      hip dysplasia and many neoplastic diseases. Therefore, longitudinal trends in
      popularity of dog morphology can reveal potential disease pervasiveness in the
      future. There have been reports on the popularity of particular breeds and
      behavioural traits but trends in the morphological traits of preferred breeds
      have not been studied. METHODS: This study investigated trends in the height, dog
      size and head shape (cephalic index) of Australian purebred dogs. One hundred
      eighty-one breeds derived from Australian National Kennel Council (ANKC)
      registration statistics from 1986 to 2013 were analysed. Weighted regression
      analyses were conducted to examine trends in the traits by using them as outcome
      variables, with year as the explanatory variable and numbers of registered dogs
      as weights. Linear regression investigated dog height and cephalic index (skull
      width/skull length), and multinomial logistic regression studied dog size.
      RESULTS: The total number of ANKC registration had decreased gradually from
      95,792 in 1986 to 66,902 in 2013. Both weighted minimal height (p = 0.014) and
      weighted maximal height (p < 0.001) decreased significantly over time, and the
      weighted cephalic index increased significantly (p < 0.001). The odds of
      registration of medium and small breeds increased by 5.3 % and 4.2 %,
      respectively, relative to large breeds (p < 0.001) and by 12.1 % and 11.0 %,
      respectively, relative to giant breeds (p < 0.001) for each 5-year block of time.
      CONCLUSIONS: Compared to taller and larger breeds, shorter and smaller breeds
      have become relatively popular over time. Mean cephalic index has increased,
      which indicates that Australians have gradually favoured breeds with shorter and
      wider heads (brachycephalic). These significant trends indicate that the dog
      morphological traits reported here may potentially influence how people select
      companion dogs in Australia and provide valuable predictive information on the
      pervasiveness of diseases in dogs.

PMID- 27051523
TI  - Inspiration of the functional localization of a US naval hospital ship on a
      Chinese hospital ship.
AB  - Through the experience of being stationed on the USS Mercy hospital ship (T-AH19)
      and a preliminary comprehension of the personnel and material arrangements,
      processing and functional formats, and the multi-platform contributions of US
      Navy hospital ships, we briefly introduce the characteristics of US hospital
      ships regarding medical support, emergency rescue exercises, communications and
      training, international humanitarian aid, etc. We discuss the function and
      responsibility of Chinese hospital ships, focusing on the investigation of the
      construction mode and positioning in the navy. 

PMID- 27051524
TI  - Population pharmacokinetic analysis and dosing regimen optimization of penicillin
      G in patients with infective endocarditis.
AB  - BACKGROUND: This study was designed to evaluate the population pharmacokinetics
      (popPK) of penicillin G in patients with infective endocarditis and establish a
      dosage regimen based on pharmacokinetic data and clinical outcome. METHOD: Forty
      six serum penicillin G samples from 25 individuals were analyzed using a
      nonlinear mixed-effects model. popPK were estimated using a one-compartment
      model. We created a receiver operating characteristic (ROC) curve for penicillin
      G efficacy and the ratio of its minimum concentration (Cmin)/minimum inhibitory
      concentration (MIC). Simulations were used to optimize the penicillin G dosage
      regimen using this ratio. RESULT: Estimated popPK were: CL (L/h) = 0.21 *
      creatinine clearance (CLcr) (mL/min), Vd (L) = 28.9. The areas under the ROC
      curves were 0.87 for clinical efficacy. The cut-off value of penicillin G
      Cmin/MIC was 60. The continuous administration of 1 million IU penicillin G/h was
      necessary to achieve a positive outcome for patients with normal renal function
      (CLcr >= 60 mL/min). CONCLUSION: Our findings suggest that population-based
      parameters are useful for evaluating penicillin G pharmacokinetics and that an
      individualized dosage should be determined based on a described dosage regimen.

PMID- 27051525
TI  - Changes of blood pressure, abdominal visceral fat tissue and gene expressions in
      fetal programming induced rat model after amlodipine-losartan combination
      treatment.
AB  - BACKGROUND: There are a number of complications that can occur if there is under
      nutrition during pregnancy followed by a period of rapid catch-up growth,
      including a higher chance of adult obesity, insulin resistance and
      hypertriglyceridemia. The purposes of this study were to investigate the effects
      of fetal under-nutrition during late pregnancy and lactation on blood pressure,
      visceral fat tissue, gene expressions and to evaluate changes after amlodipine-
      losartan combination treatment. METHODS: The rats were divided into three groups:
      the control (C) group, the food restriction (FR: 50 % food restricted diet)
      group, and the CX group, which was treated with Cozaar XQ (amlodipine- losartan
      combination drug) in FR rats from postnatal 4 to 20 weeks. Masson's trichrome
      staining was performed in the heart tissues. The amount of abdominal visceral fat
      tissues was measured. Western blot analysis such as angiotensin converting enzyme
      (ACE), angiotensin II receptor type IA (ATIA), troponin I (Tn I) and endothelial
      nitric oxide synthase (eNOS) were performed. RESULTS: Body weights were
      significantly higher in the FR group compared with the C group at weeks 8 and 20
      and lower in the CX group at week 20. Blood pressure was significantly higher in
      the FR group compared with the C group at week 20 and lower in the CX group at
      weeks 12 and 20. The amount of abdominal visceral fat was significantly higher in
      the FR group compared with the C group at weeks 8, 12 and 20 and significantly
      lower in the CX group at weeks 16 and 20. Protein expression of ATIA and eNOS
      were significantly reduced in the CX group at weeks 16 and 20. ACE was
      significantly reduced in the CX group at week 20 and Tn I was significantly
      reduced in the CX group at week 16. CONCLUSIONS: When there is fetal under
      nutrition during pregnancy, it leads to obesity, high blood pressure,
      hypertriglyceridemia and several gene changes in offspring. Amlodipine-losartan
      combination treatment was able to lower obesity, hypertension,
      hypertriglyceridemia and several gene changes in rats suffering from fetal under
      nutrition during pregnancy.

PMID- 27051526
TI  - Changes of Corneal Wavefront Aberrations in Dry Eye Patients after Treatment with
      Artificial Lubricant Drops.
AB  - Purpose. To evaluate the corneal aberration changes in dry eye patients after
      treatment with artificial eye drops. Methods. Thirty mild to moderate dry eye
      patients treated with artificial eye drops and twenty comparable dry eye patients
      were recruited as controls. Anterior corneal aberrations over 3 mm and 5 mm
      analytical zones including total, 3rd to 5th high order aberrations (HOAs),
      spherical aberration (SA), and vertical (V-coma) and horizontal coma (H-coma)
      obtained from corneal topography data at baseline and 2 weeks after treatment
      were evaluated. Results. For 3 mm zone, trefoils, V-coma, H-coma terms, and 3rd
      and 5th HOAs were significantly decreased (p < 0.05) in the treatment group. For
      5 mm zone, instillation of eye drops reduced H-coma, SA terms, 3rd to 5th orders,
      and total HOAs all showed a significant decrease (p < 0.05). The root mean square
      analysis of the Zernike terms also showed similar statistical results. For
      control group, all individual terms and total HOAs did not have significant
      changes over 3 mm and 5 mm zones (p > 0.05). Conclusions. Treatment with
      artificial eye drops can effectively improve the corneal optical quality of dry
      eye patients by ameliorating the HOAs of anterior corneal surface. 

PMID- 27051527
TI  - Corneal-Based Surgical Presbyopic Therapies and Their Application in Pseudophakic
      Patients.
AB  - Purpose. The purpose of this review is to provide a summary of laser refractive
      surgery and corneal inlay approaches to treat presbyopia in patients after
      cataract surgery. Summary. The presbyopic population is growing rapidly along
      with increasing demands for spectacle independence. This review will focus on the
      corneal-based surgical options to address presbyopia including various types of
      corneal intrastromal inlays and laser ablation techniques to generate either a
      multifocal cornea ("PresbyLASIK") or monovision. The natural history of
      presbyopia develops prior to cataracts, and these presbyopic surgeries have been
      largely studied in phakic patients. Nevertheless, pseudophakic patients may also
      undergo these presbyopia-compensating procedures for enhanced quality of life.
      This review examines the published reports that apply these technologies to
      patients after cataract surgery and discusses unique considerations for this
      population. 

PMID- 27051528
TI  - Impulsivity, Sensation Seeking, and Risk-Taking Behaviors among HIV-Positive and
      HIV-Negative Heroin Dependent Persons.
AB  - Objective. The aim of this study was to compare impulsivity and risky decision
      making among HIV-positive and negative heroin dependent persons. Methods. We
      compared different dimensions of impulsivity and risky decision making in two
      groups of 60 HIV-positive and 60 HIV-negative male heroin dependent persons. Each
      group was comprised of equal numbers of current (treatment seeker) and former
      (abstinent) heroin addicts. Data collection tools included Balloon Analogue Risk
      Task (BART), Iowa Gambling Task (IGT), Barratt Impulsiveness Scale (BIS), and
      Zuckerman Sensation Seeking Scale (SSS). Results. In SSS, comprised of four
      subscales including thrill and adventure seeking (TAS), experience seeking (ES),
      disinhibition (DIS), and boredom susceptibility (BS), there was a borderline
      difference in DIS (P = 0.08) as HIV-positive group scored higher than HIV
      negative group. Also, ES and total score were significantly higher among HIV
      positive patients. In BART, HIV-positive subjects scored higher in risk taking
      than HIV-negative subjects as reflected in higher Average Number of puffs in
      Successful Balloons (ANSB). In BIS, HIV-positive group scored significantly
      higher in cognitive impulsivity (CI) (P = 0.03) and nonplanning impulsivity (NPI)
      (P = 0.05) in comparison to HIV-negative group. Also, current heroin addicts
      scored significantly higher in NPI compared to former addict HIV-negative
      participants (P = 0.015). IGT did not show any significant difference between
      groups. Conclusion. Higher levels of impulsivity and risk taking behaviors among
      HIV-positive heroin addicts will increase serious concerns regarding HIV
      transmission from this group to other opiate dependents and healthy people. 

PMID- 27051529
TI  - Medicinal Herbals with Antiplatelet Properties Benefit in Coronary
      Atherothrombotic Diseases.
AB  - Coronary atherothrombotic diseases such as coronary artery disease, peripheral
      vascular disease, cerebrovascular disease, and heart failure are the serious
      concerns of the thrombus formed in blood vessels. Anticoagulant and antiplatelet
      drugs are the cornerstones of the management of these diseases. To prevent the
      recurrence of these diseases, double antiplatelet drugs such as aspirin and
      clopidogrel has been the standard management in most hospitals. However, aspirin
      resistance and clopidogrel inefficient effects due to noncompliance with double
      drugs regimen can cause a sinister effect on patients. Medicinal plants serve as
      a greater resource for new medication and their potential currently became a
      topic of interest to the researchers all over the world. Traditionally, certain
      herbs have been used as a treatment for heart diseases but have been investigated
      for their antiplatelet properties. This current review explained few traditional
      antithrombotic herbals and their antiplatelet properties in vitro and in vivo and
      this is to be deeply discussed in further research. 

PMID- 27051530
TI  - New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents.
AB  - Considering quinoxaline as a privileged structure for the design of potent
      intercalating agents, some new sugar conjugates of quinoxaline were synthesized
      and characterized by IR, (1)HNMR, (13)C NMR, and mass spectral data. In vitro
      testing for antitubercular and antimicrobial activities was performed against
      Mycobacterium tuberculosis H 37 Rv and some pathogenic bacteria. Results revealed
      that conjugate containing ribose moiety demonstrated the most promising activity
      against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC) of
      0.65 and 2.07 MUM, respectively. Other conjugates from xylose, glucose, and
      mannose were moderately active whilst disaccharides conjugates were found to be
      less active. In silico docking analysis of prototype compound revealed that ATP
      site of DNA gyrase B subunit could be a possible site for inhibitory action of
      these synthesized compounds. 

PMID- 27051531
TI  - Molecular Characterization of Human Rotavirus from Children with Diarrhoeal
      Disease in Sokoto State, Nigeria.
AB  - This study was conducted to detect and characterize prevalent human group A
      rotavirus strains from 200 diarrheic children in Sokoto, Nigeria, by ELISA,
      monoclonal antibody (Mab) serotyping and Reverse Transcription-Polymerase Chain
      Reaction (RT-PCR) techniques. Rotavirus was detected in 25.5% of the children.
      The G-serotypes observed in circulation were G4: 16 (59.3%), G1: 4 (14.8%), G2: 3
      (11.1%), G3: 3 (11.1%), and G12: 1 (3.7%). The monoclonal antibody (Mab)
      serotyping detected G1 and G3 but did not detect G4 and G2 serotypes. The Mab
      typing of the G1 and G3 serotypes was consistent with the result of the RT-PCR.
      The VP4 genotypes detected were P[6] 3 (13%), P[8] 11 (47.8%), and the rare human
      P genotype (P[9]), found in 9 patients (39.1%). Nine strains identified with the
      common G and P combinations were G4 P[8] 5 (56%), G4 P[6] 1 (11%), G1 P[8] 2
      (22%), and G3 P[8] 1 (11%), while seven strains with unusual combinations or rare
      G or P genotypes identified were G12 P[8] 1 (14%), G2 P[8] 2 (29%), and G4 P[9] 4
      (57%). To our knowledge this is the first molecular study of human rotavirus and
      report of rare human G and P serotypes in Sokoto State. 

PMID- 27051532
TI  - Changes in Lipid Profiles of HIV(+) Adults over Nine Months at a Harare HIV
      Clinic: A Longitudinal Study.
AB  - HIV infection, together with ART, is associated with changes in biochemical,
      metabolic parameters and lipid profiles. The aim of this study was to compare
      changes in lipid profiles among HIV positive outpatients over nine months. 171
      patients were investigated, 79% were ART experienced, and 82% of ART experienced
      patients were on NVP/EFV first line at baseline, but some patients changed ART
      groups over follow-up and classification was based on intent to treat. More than
      60% ART naive and ART experienced patients had some form of dyslipidemia either
      at baseline or at follow-up, but mean lipid values for the two groups were within
      normal limits. At baseline and follow-up, mean levels of TC and HDL were slightly
      higher in the ART experienced group. Interestingly, there was higher increase in
      HDL over time in the ART negative group compared to the ART positive group. There
      was a decrease in TC/HDL ratio in both groups over time, suggesting a reduction
      in calculated risk of CHD over time. HIV positive patients frequently show
      various forms of dyslipidemia, but there are no changes in average atherogenic
      lipid levels and results suggest reduced risk of CHD, mainly due to increases in
      HDL, after nine months of observation time. 

PMID- 27051533
TI  - Paramedic Recognition of Sepsis in the Prehospital Setting: A Prospective
      Observational Study.
AB  - Background. Patients with sepsis benefit from early diagnosis and treatment.
      Accurate paramedic recognition of sepsis is important to initiate care promptly
      for patients who arrive by Emergency Medical Services. Methods. Prospective
      observational study of adult patients (age >= 16 years) transported by paramedics
      to the emergency department (ED) of a Canadian tertiary hospital. Paramedic
      identification of sepsis was assessed using a novel prehospital sepsis screening
      tool developed by the study team and compared to blind, independent documentation
      of ED diagnoses by attending emergency physicians (EPs). Specificity,
      sensitivity, accuracy, positive and negative predictive value, and likelihood
      ratios were calculated with 95% confidence intervals. Results. Overall, 629
      patients were included in the analysis. Sepsis was identified by paramedics in
      170 (27.0%) patients and by EPs in 71 (11.3%) patients. Sensitivity of paramedic
      sepsis identification compared to EP diagnosis was 73.2% (95% CI 61.4-83.0),
      while specificity was 78.8% (95% CI 75.2-82.2). The accuracy of paramedic
      identification of sepsis was 78.2% (492/629, 52 true positive, 440 true
      negative). Positive and negative predictive values were 30.6% (95% CI 23.8-38.1)
      and 95.9% (95% CI 93.6-97.5), respectively. Conclusion. Using a novel prehospital
      sepsis screening tool, paramedic recognition of sepsis had greater specificity
      than sensitivity with reasonable accuracy. 

PMID- 27051534
TI  - Pelvic Radiotherapy versus Radical Prostatectomy with Limited Lymph Node Sampling
      for High-Grade Prostate Adenocarcinoma.
AB  - Purpose. To compare oncologic outcomes for patients with Gleason score (GS) >= 8
      prostate adenocarcinoma treated with radical prostatectomy (RP) versus external
      beam radiotherapy combined with androgen deprivation (RT + ADT). Methods. Between
      2001 and 2014, 121 patients with GS >= 8 were treated at our institution via RT +
      ADT (n = 71) or RP (n = 50) with >= 1 year of biochemical follow-up. Endpoints
      included biochemical failure (BF), distant metastasis, and initiation of salvage
      ADT. Results. The RT + ADT group was older, had higher biopsy GS, and had greater
      risk of lymph node involvement. All other pretreatment characteristics were
      similar between groups. Mean number of lymph nodes (LNs) sampled for patients
      undergoing RP was 8.2 (+/-6.18). Mean biochemical follow-up for all patients was
      61 months. Five-year estimates of BF for the RT + ADT and RP groups were 7.2%
      versus 42.3%, (p < 0.001). The RT + ADT group also had lower rates of distant
      metastasis (2% versus 7.8%) and salvage ADT (8% versus 33.8%). Conclusion. In
      this analysis, RT + ADT was associated with improved biochemical and metastatic
      control when compared to RP with limited LN sampling. How RT + ADT compares with
      more aggressive lymphadenectomy, as is currently our institutional standard,
      remains an important unanswered question. 

PMID- 27051535
TI  - Length of Individual Apnea Events Is Increased by Supine Position and Modulated
      by Severity of Obstructive Sleep Apnea.
AB  - Positional obstructive sleep apnea (OSA) is common among OSA patients. In severe
      OSA, the obstruction events are longer in supine compared to nonsupine positions.
      Corresponding scientific information on mild and moderate OSA is lacking. We
      studied whether individual obstruction and desaturation event severity is
      increased in supine position in all OSA severity categories and whether the
      severity of individual events is linked to OSA severity categories. Polygraphic
      recordings of 2026 patients were retrospectively analyzed. The individual apnea,
      and hypopnea durations and desaturation event depth, duration, and area of 526
      included patients were compared between supine and nonsupine positions in
      different OSA severity categories. Apnea events were 6.3%, 12.5%, and 11.1%
      longer (p < 0.001) in supine compared to nonsupine position in mild, moderate,
      and severe OSA categories, respectively. In moderate and severe OSA categories
      desaturation areas were 5.7% and 25.5% larger (p < 0.001) in supine position. In
      both positions the individual event severity was elevated along increasing OSA
      severity category (p < 0.05). Supine position elevates apnea duration in all and
      desaturation area in moderate and severe OSA severity categories. This might be
      more hazardous for supine OSA patients and therefore, estimation of clinical
      severity of OSA should incorporate also information about individual event
      characteristics besides AHI. 

PMID- 27051536
TI  - Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders.
AB  - Affective disorders are a leading cause of disabilities worldwide, and the
      etiology of these many affective disorders such as depression and posttraumatic
      stress disorder is due to hormone changes, which includes hypothalamus-pituitary
      adrenal axis in the peripheral nervous system and neuromodulators in the central
      nervous system. Consistent with pharmacological studies indicating that medical
      treatment acts by increasing the concentration of catecholamine, the locus
      coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the
      central "stress circuitry," whose major function is to induce "fight or flight"
      behavior and fear and anger emotion. Despite the intensive studies, there is
      still controversy about NE with fear and anger. For example, the rats with LC
      ablation were more reluctant to leave a familiar place and took longer to consume
      the food pellets in an unfamiliar place (neophobia, i.e., fear in response to
      novelty). The reason for this discrepancy might be that NE is not only for flight
      (fear), but also for fight (anger). Here, we try to review recent literatures
      about NE with stress induced emotions and their relations with mental disorders.
      We propose that stress induced NE release can induce both fear and anger.
      "Adrenaline rush or norepinephrine rush" and fear and anger emotion might act as
      biomarkers for mental disorders. 

PMID- 27051537
TI  - Child Who Presented with Facial Hematohidrosis Compared with Published Cases.
AB  - Hematohidrosis is a rare condition in which an individual sweats blood from
      intact, unbroken skin. The aetiology of hematohidrosis is not clear, although
      various theories exist to explain such a phenomenon. The general consensus
      however in the literature relates the finding to dermal capillary blood vessels
      that rupture under extreme emotional or physical stress exuding blood through the
      skin. In this case report we disclose a case of 12-year-old girl who presented
      with unusual painless bleeding from her face, eye, and tear duct. The condition
      was investigated intensively during hospital admission for a cause, and no actual
      cause was speculated. The management mostly involved supportive care and medical
      advice. 

PMID- 27051538
TI  - Amyloid Goiter Secondary to Ulcerative Colitis.
AB  - Diffuse amyloid goiter (AG) is an entity characterized by the deposition of
      amyloid in the thyroid gland. AG may be associated with either primary or
      secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory
      bowel diseases. Secondary amyloidosis is relatively more common in the patients
      with Crohn's disease, whereas it is highly rare in patients with ulcerative
      colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare
      condition. In the presence of amyloid in the thyroid gland, medullary thyroid
      cancer should be kept in mind in the differential diagnosis. Imaging techniques
      and biochemical tests are not very helpful in the diagnosis of secondary amyloid
      goiter and the definitive diagnosis is established based on the histopathologic
      analysis and histochemical staining techniques. In this report, we present a 35
      year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis
      associated with ulcerative colitis. 

PMID- 27051539
TI  - Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System
      Tuberculoma.
AB  - Tuberculosis (TB) is a serious infectious disease that spreads globally. The
      ocular manifestations of TB are uncommon and diverse. TB panophthalmitis has been
      rarely reported. Here, we described a 38-year-old Thai man presenting with
      panophthalmitis of the right eye. Further investigation showed that he had
      concurrent TB lymphadenitis and central nervous system (CNS) tuberculoma, as well
      as HIV infection, with a CD4 cell count of 153 cells/mm(3). Despite the initial
      response to antituberculous agents, the disease had subsequently progressed and
      enucleation was required. The pathological examination revealed acute suppurative
      granulomatous panophthalmitis with retinal detachment. Further staining
      demonstrated acid-fast bacilli in the tissue. Colonies of Mycobacterium
      tuberculosis were obtained from tissue culture. He was treated with
      antiretroviral agents for HIV infection and 12 months of antituberculous agents.
      Clinicians should be aware of the possibility of TB in the differential diagnosis
      of endophthalmitis and panophthalmitis, especially in regions where TB is
      endemic. 

PMID- 27051540
TI  - A Rare Case Report on Suboccipital Region Benign Giant Osteoma.
AB  - Herein we report a rare case of a giant suboccipital osteoma in a 55-year-old
      woman presenting primarily due to cosmetic issue. We discuss the management
      algorithm taken in the patient, highlighting excision of a potentially curable
      bony tumor only after ruling out its extension to the ear cavity, mastoid ear
      cells, transverse sinus, and the intracranial compartment. 

PMID- 27051542
TI  - Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic
      Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus.
AB  - Infection, whether viral or bacterial, can result in various forms of brain
      dysfunction (encephalopathy). Septic encephalopathy (SE) is caused by an
      excessive immune reaction to infection, with clinical features including
      disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures
      and late reduced diffusion (AESD) is usually accompanied by viral infection in
      children and is characterized by biphasic seizures and impaired consciousness.
      The initial neurologic symptom of AESD is typically a febrile seizure that
      frequently lasts longer than 30 minutes. However, the possible forms this seizure
      takes are unclear. For example, it is unknown if nonconvulsive status epilepticus
      (NCSE) could be an early seizure symptomatic of AESD. In addition, thus far no
      cases of combined SE and AESD have been reported. Here, we describe the first
      reported case of SE with AESD that notably demonstrated NCSE as an early seizure.

PMID- 27051541
TI  - Spinal Cord Infarction in a Patient with Hereditary Spherocytosis: A Case Report
      and Discussion.
AB  - The etiology of spinal cord infarcts (SCIs), besides being related to aortic
      perioperative events, in large subset of SCIs, remains cryptogenic. We present a
      first case of SCI in a patient with hereditary spherocytosis and discuss the
      potential pathophysiologic considerations for vascular compromise. A 43-year-old
      woman with a history of hereditary spherocytosis, post splenectomy status,
      presented with chest, back, and shoulder pain with subsequent myelopathic
      picture; SCI extending from C4-T2 was confirmed by MRI. Despite aggressive
      treatment her stroke progressed leading to her demise. Her autopsy confirmed the
      SCI and revealed some incidental findings, but the cause of SCI remained
      unidentified. Exclusion of the known etiologies of SCI by extensive negative
      workup including autopsy evaluation suggested that SCI in our case was related to
      her history of hereditary spherocytosis. Both venous and arterial adverse
      vascular events, at a higher rate, have been associated in patients with
      hereditary spherocytosis who had their spleens removed compared to
      nonsplenectomized patients. Postsplenectomy increases in the platelet, red blood
      cell count, leukocyte count, and cholesterol concentrations are postulated to
      contribute to increased thrombotic risk. Additional prothrombotic factors include
      continuous platelet activation and adhesion as well as abnormalities of the red
      blood cell membrane. 

PMID- 27051543
TI  - Staphylococcus lugdunensis Endocarditis in a 35-Year-Old Woman in Her 24th Week
      of Pregnancy.
AB  - Background. Infective endocarditis is associated with considerable morbidity and
      mortality. Guidelines addressing prophylaxis and management of infective
      endocarditis do not extensively deal with concomitant pregnancy, and case reports
      on infective endocarditis are scarce. This is the first published report of
      infective endocarditis by Staphylococcus lugdunensis in a pregnant woman. Case
      Presentation. We report a single case of a 35-year-old woman in her 24th week of
      pregnancy who was admitted to our intensive care unit with fever and suspected
      infectious endocarditis. Blood culture detected Staphylococcus lugdunensis. A
      vegetation and severe mitral regurgitation due to complete destruction of the
      valve confirmed the diagnosis. An interdisciplinary panel of cardiologists,
      maternal-fetal medicine specialists, cardiac and plastic surgeons,
      infectiologists, anesthesiologists, and neonatologists was formed to determine
      the best therapeutic strategy. Conclusions. Timing and indications for surgical
      intervention to prevent embolic complications in infective endocarditis remain
      controversial. This original case report illustrates how managing infective
      endocarditis by Staphylococcus lugdunensis particularly in the 24th week of
      pregnancy can represent a therapeutic challenge to a broad section of specialties
      across medicine. Critical cases like this require a thorough weighing of risks
      and benefits followed by swift action to protect the mother and her unborn child.

PMID- 27051544
TI  - Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing
      Carboplatin Chemotherapy.
AB  - Background. Diarrhea is a common problem in ovarian cancer patients undergoing
      chemotherapy and Clostridium difficile infection has been identified as a cause.
      The proper diagnosis and treatment of diarrhea are critical to patient care,
      especially to prevent the serious complications from a severe Clostridium
      difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer
      patient who developed recurrent pseudomembranous colitis while receiving
      carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen
      days, the patient's diarrhea relapsed and colonoscopy revealed extensive
      pseudomembranous colitis. The infection eventually resolved with the combination
      of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem
      in patients undergoing chemotherapy for ovarian cancer. Management requires
      obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous
      colitis must be part of the differential diagnosis. Treatment must be sufficient
      to prevent relapses of the Clostridium difficile infection to prevent serious
      consequences in an already vulnerable patient population. 

PMID- 27051545
TI  - Lassa Fever in Pregnancy: Report of 2 Cases Seen at the University College
      Hospital, Ibadan.
AB  - Lassa fever (LF), an acute viral haemorrhagic fever, is an endemic zoonotic viral
      infection in West Africa countries with up to 15% case fatality rate. Though a
      rodent-borne infection, it can also be transmitted from person to person during
      the care of sick relations or more commonly in health care settings as a
      nosocomial infection. Vertical transmission from mother to child has been
      documented. We report 2 cases of LF among pregnant women which were managed at
      the University College Hospital, Ibadan, between September and October 2014. Both
      patients were in their early 20s with only one surviving the disease. Both had
      supportive therapy but none had antiviral therapy. This report emphasized the
      importance of early presentation, high index of suspicion, prompt diagnosis, and
      early commencement of supportive therapy in the management of patients suspected
      with LF especially in the era of other viral haemorrhagic infections. 

PMID- 27051546
TI  - A Rare Case of Bipolar Clavicle Fracture.
AB  - Segmental or bipolar fractures of the clavicle generally refer to a concomitant
      ipsilateral distal clavicle and midshaft clavicle fracture. These injuries are
      exceedingly rare and are generally secondary to higher energy injuries. We report
      a case of a 38-year-old male who sustained a left bipolar clavicle fracture after
      falling from a push bike while riding recreationally which unusually involved the
      medial and lateral ends of the clavicle and not the midshaft as previously
      reported in other patients. The patient's exact fracture configuration was not
      immediately apparent highlighting the need for careful examination of the whole
      clavicle in order to not miss a bipolar fracture. 

PMID- 27051547
TI  - An Unexpected Complication after Headless Compression Screw Fixation of an
      Osteochondral Fracture of Patella.
AB  - This study evaluated complications associated with implant depth in headless
      compression screw treatment of an osteochondral fracture associated with a
      traumatic patellar dislocation in a 21-year-old woman. Computed tomography and X
      rays showed one lateral fracture fragment measuring 25 * 16 mm. Osteosynthesis
      was performed with two headless compression screws. Five months later, the screws
      were removed because of patella-femoral implant friction. We recommend that the
      screw heads be embedded to a depth of at least 3 mm below the cartilage surface.
      Further clinical studies need to examine the variation in cartilage thickness in
      the fracture fragment. 

PMID- 27051548
TI  - FPIES: Reviewing the Management of Food Protein-Induced Enterocolitis Syndrome.
AB  - Purpose of Review. The aim of this review is to provide a case driven
      presentation of the presenting features and diagnostic criteria particularly
      focusing on the management of FPIES. It also summarises the natural history and
      resolution of cow's milk induced FPIES. Data Sources. OvidSP Database was used to
      search for literature using the keywords food protein-induced enterocolitis and
      FPIES. Recent Findings. The diagnosis of FPIES is often delayed following two or
      more presentations. Symptoms in the acute form include profuse vomiting usually 2
      6 hours following ingestion of food. Vomiting may or may not be accompanied by
      diarrhoea. Management involves removing the causal food protein from diet. There
      is some concomitance in cow's milk and soya induced FPIES. Hence extensively
      hydrolysed formula is the milk of choice unless breast-feeding is carried out in
      which case that should be continued. Summary. FPIES is a complex form of non-IgE
      mediated food allergy. More awareness and knowledge of the condition are required
      to prevent misdiagnosis. Early diagnosis and removal of the culprit food protein
      improve the outcome. Good nutritional advice and clear management plans are
      important. More multicentre studies are required to reevaluate and produce
      consistent oral food challenge criteria and guidelines. 

PMID- 27051549
TI  - Chronic Osteomyelitis of Clavicle in a Neonate: Report of Morbid Complication of
      Adjoining MRSA Abscess.
AB  - Osteomyelitis of clavicle is rare in neonates. Acute osteomyelitis of clavicle
      accounts for less than 3% of all osteomyelitis cases. It may occur due to
      contiguous spread, due to hematogenous spread, or secondary to subclavian
      catheterization. Chronic osteomyelitis may occur as a complication of residual
      adjoining abscess due to methicillin resistant staphylococcus aureus (MRSA)
      sepsis. We report a newborn female with right shoulder abscess that developed
      chronic clavicular osteomyelitis in follow-up period after drainage. She required
      multiple drainage procedures and was later successfully managed with bone
      curettage and debridement. We report this case to highlight that a MRSA abscess
      may recur due to residual infection from a chronic osteomyelitis sinus. It may be
      misdiagnosed as hypergranulation tissue of nonhealing wound leading to
      inappropriate delay in treatment. High index of suspicion, aggressive initial
      management, and regular follow-up are imperative to prevent this morbid
      complication. 

PMID- 27051550
TI  - Targeted Nutritional and Behavioral Feeding Intervention for a Child with Autism
      Spectrum Disorder.
AB  - A variety of feeding issues and concerns, including food aversion, food
      selectivity, and complete food refusal, are not uncommon among children with
      autism spectrum disorder (ASD). Other underlying issues are often comorbid with
      the concerns for feeding and ASD. These may include food allergies,
      gastrointestinal issues, oral motor issues, and swallowing disorders. The refusal
      to consume particular foods coupled with the inability to tolerate, digest, and
      absorb these foods can compromise an individual's overall nutrition status.
      Therefore, a child's behavior toward food and feeding activities has great impact
      on dietary intake, nutritional status, and growth. This case report is the first
      to document combined medical, behavioral, and nutritional intervention for a
      toddler with ASD and comorbid feeding disorder. 

PMID- 27051551
TI  - Outcomes of Patients Who Have Do Not Resuscitate Status prior to Being Admitted
      to an Intensive Care Unit.
AB  - Admission of patients who have do not resuscitate (DNR) status to an intensive
      care unit (ICU) is potentially a misallocation of limited resources to patients
      who may neither need nor want intensive care. Yet, patients who have DNR status
      are often admitted to the ICU. This is a retrospective review of patients who had
      a valid DNR status at the time that they were admitted to an ICU in a single
      hospital over an eighteen-month period. Thirty-five patients met the criteria for
      inclusion in the study. The primary reasons for admission to the ICU were
      respiratory distress (54.2%) and sepsis (45.7%). Sixteen (45.7%) of the patients
      died, compared to a 5.4% mortality rate for all patients admitted to our ICU
      during this period (p < 0.001). APACHE II score was a significant predictor of
      mortality (18.5 +/- 1.3 alive and 23.4 +/- 1.4 dead; p = 0.038). Of the 19
      patients discharged alive, 9 were discharged home, 5 to hospice, and 4 to a post
      acute care facility. Conclusions. Patients who have DNR status and are admitted
      to the ICU have a higher mortality than other ICU patients. Those who survive
      have a high likelihood of being discharged to hospice or a post-acute care
      facility. The value of intensive intervention for these patients is not supported
      by these results. Only a minority of patients were seen by palliative care and
      chaplain teams, services which the literature supports as valuable for DNR
      patients. Our study supports the need for less expensive and less intensive but
      more appropriate resources for patients and families who have chosen DNR status. 

PMID- 27051552
TI  - Role of MMP-2 (-1306 C/T) Polymorphism in Pituitary Adenoma.
AB  - Purpose. To determine if the frequency of the genotype of MMP-2 (-1306 C/T)
      Rs243865 has an influence on the development of pituitary adenoma (PA). Methods.
      The study enrolled n = 84 patients with PA and a random sample of the population
      n = 318 (reference group). The genotyping test of MMP-2 (-1306 C/T) was carried
      out using the real-time polymerase chain reaction method. Results. Analysis of
      MMP-2 (-1306 C/T) gene polymorphism has not revealed any differences in the
      genotype (C/C, C/T, and T/T) distribution between the PA patients and the
      reference group (as follows: 50%, 44%, and 6% versus 59.75%, 33.96%, and 6.29%).
      MMP-2 (-1306) C/C genotype was rarely observed in noninvasive PA compared to
      healthy controls: 35.1% versus 59.75%; p = 0.0049, as well C/C genotype being
      more frequently detected in nonrecurrence PA compared to healthy controls: 46.5%
      versus 59.75%; p = 0.0468. MMP-2 (-1306) C/T genotype was more frequently present
      in PA females compared to healthy controls females: 49.1% versus 33.66%; p =
      0.041. Conclusion. Patients with noninvasive and nonrecurrence pituitary adenoma
      were the carriers of the C/C genotype significantly more frequently than their
      control counterparts and the C/T genotype in females was more frequent. 

PMID- 27051553
TI  - Evaluation of Plaid Models in Biclustering of Gene Expression Data.
AB  - Background. Biclustering algorithms for the analysis of high-dimensional gene
      expression data were proposed. Among them, the plaid model is arguably one of the
      most flexible biclustering models up to now. Objective. The main goal of this
      study is to provide an evaluation of plaid models. To that end, we will
      investigate this model on both simulation data and real gene expression datasets.
      Methods. Two simulated matrices with different degrees of overlap and noise are
      generated and then the intrinsic structure of these data is compared with
      biclusters result. Also, we have searched biologically significant discovered
      biclusters by GO analysis. Results. When there is no noise the algorithm almost
      discovered all of the biclusters but when there is moderate noise in the dataset,
      this algorithm cannot perform very well in finding overlapping biclusters and if
      noise is big, the result of biclustering is not reliable. Conclusion. The plaid
      model needs to be modified because when there is a moderate or big noise in the
      data, it cannot find good biclusters. This is a statistical model and is a quite
      flexible one. In summary, in order to reduce the errors, model can be manipulated
      and distribution of error can be changed. 

PMID- 27051554
TI  - Granulomatous Mastitis: Imaging of Temporal Evolution.
AB  - Aim. To assess the temporal imaging evolution of granulomatous mastitis and to
      review imaging findings. Material and Methods. Retrospective review of imaging
      data of 10 patients with biopsy proven granulomatous mastitis. The patients were
      divided into 3 groups according to their initial imaging presentation. Temporal
      evolution of imaging findings was observed separately for each group. Ratios,
      proportions, and percentages were used for data analysis. Results. Upon initial
      presentation, 75% of women who underwent mammogram showed an area of mass like
      architectural distortion. 25% demonstrated focal asymmetry. Complex cystic lesion
      was seen 40%. Multiple abscesses with sinus tract formation tracking into
      surrounding tissues were seen in 2 cases. Four out of 10 patients presented as
      edematous changes. Three out of this group progressed to develop complex cystic
      lesions/abscess formation. 25% presenting with complex cystic lesions or abscess
      at presentation showed spontaneous resolution. The remainder needed surgical
      treatment. The patients with abscess formation and sinus tract formation needed
      surgical management. Conclusion. Initial imaging findings in granulomatous
      mastitis can be variable but the eventual course and outcome is similar in most
      patients with surgical management required in most cases. 

PMID- 27051555
TI  - Revelation of ZnS Nanoparticles Induces Follicular Atresia and Apoptosis in the
      Ovarian Preovulatory Follicles in the Catfish Mystus tengara (Hamilton, 1822).
AB  - Important physicochemical characteristics of water like dissolved oxygen content,
      pH, and so forth were found to change in a dose dependent manner, showing a
      negative correlation with the nanoparticle concentration, when ZnS nanoparticle
      (NP) was exposed to water. This observation could be attributed to the enhanced
      photooxidation property associated with ZnS in its NP form. Under this situation,
      the catfish Mystus tengara was forced to live in hypoxia in its habitat. This
      condition was found to hamper the natural oogenesis process of the fish. Due to
      exposure at relatively lower concentration of ZnS NPs (250 MUg/L), most of the
      maturing follicles of M. tengara failed to complete the process of vitellogenesis
      properly and underwent preovulatory atresia followed by oocytic apoptosis. For
      relatively higher concentration of ZnS nanoparticles (500 MUg/L), the
      previtellogenic process continued with increasing number of apoptotic cells;
      however the vitellogenic process was found to be totally blocked. This unusual
      reproductive behaviour in female M. tengara can be attributed to the decreased
      metabolism of the fishes under ZnS nanoparticle induced hypoxia. 

PMID- 27051556
TI  - Effect of Various Sugary Beverages on Salivary pH, Flow Rate, and Oral Clearance
      Rate amongst Adults.
AB  - Introduction. Diet is a major aetiological factor for dental caries and enamel
      erosion. This study was undertaken with the aim of assessing the effect of
      selected locally available beverages on salivary pH, flow rate, and oral
      clearance rate amongst adults. Materials and Method. This clinical trial
      comprised 120 subjects. Test beverages undertaken were pepsi, fruit drink,
      coffee, and sweetened milk. Statistical analysis was carried out using SPSS
      version 17. Descriptive statistics, one-way ANOVA, and post hoc Tukey's test were
      applied in the statistical tests. Results. It was found that salivary pH
      decreased for all the beverages immediately after consumption and the salivary
      flow rate increased after their consumption. The oral clearance rate of sweetened
      milk was found to be the least at 6.5 minutes and that of pepsi was found to be
      13 minutes. However, the oral clearance rates of fruit drink and coffee were
      found to be equal at 15 minutes. Conclusion. Although it was found out that
      liquids cleared rapidly from the oral cavity, they had a significant cariogenic
      and erosive potential. Hence, it is always advised to minimise the consumption of
      beverages, especially amongst children and young adults to maintain a good oral
      health. 

PMID- 27051557
TI  - SNP Microarray in FISH Negative Clinically Suspected 22q11.2 Microdeletion
      Syndrome.
AB  - The present study evaluated the role of SNP microarray in 101 cases of clinically
      suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome.
      SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or
      CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions
      and/or microduplications in addition to cases of chromosomal abnormalities and
      other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions
      (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly
      from FISH noninformative cases. This study also identified several LOH/AOH loci
      with known and well-defined UPD (uniparental disomy) disorders. In conclusion,
      this study suggests more strict clinical criteria for FISH analysis. However, if
      clinical criteria are few or doubtful, in particular newborn/neonate in intensive
      care, SNP microarray should be the first screening test to be ordered. FISH is
      ideal test for detecting mosaicism, screening family members, and prenatal
      diagnosis in proven families. 

PMID- 27051558
TI  - Changes in Mitral Annular Ascent with Worsening Echocardiographic Parameters of
      Left Ventricular Diastolic Function.
AB  - Background. While the mitral annular plane systolic excursion (MAPSE) has been
      suggested as a surrogate measurement of left ventricular ejection fraction, less
      is known about the relative value of mitral annular ascent (MAa). Methods. Our
      database was queried for complete transthoracic echocardiograms performed for any
      clinical indication. Baseline echocardiographic measurements were compared to
      determine any correlation between MAa and traditional Echo-Doppler
      echocardiographic measures to characterize left ventricular diastolic dysfunction
      (LVDD). Results. Patients with normal LV diastolic function were younger (41 +/-
      13 years) than patients with LVDD (stage 1: 61 +/- 13 years; stage 2: 57 +/- 14
      years; and stage 3: 66 +/- 17 years; p = 0.156). LV ejection fraction decreased
      in patients with stage 2 LVDD (63 +/- 17%) and was further reduced in patients
      with stage 3 LVDD (28 +/- 21; p = 0.003). Discussion. While a vigorous MAa
      excursion was seen in patients with stage 1 LVDD, MAa significantly decreased in
      stage 2 and stage 3 LVDD patients. Our results highlight the importance of
      atrioventricular coupling, as MAa motion seems to reflect changes in left atrial
      pressure. Additional studies are now required to better examine atrioventricular
      interactions and electromechanical coupling that might improve our assessment of
      LV diastolic function. 

PMID- 27051559
TI  - Comparison of Antimicrobial Activity of Chlorhexidine, Coconut Oil, Probiotics,
      and Ketoconazole on Candida albicans Isolated in Children with Early Childhood
      Caries: An In Vitro Study.
AB  - Background. Early childhood caries (ECC) is associated with early colonisation
      and high levels of cariogenic microorganisms. With C. albicans being one of
      those, there is a need to determine the effectiveness of various chemotherapeutic
      agents against it. The study is aimed at isolating Candida species in children
      with ECC and at studying the antifungal effect of coconut oil, probiotics,
      Lactobacillus, and 0.2% chlorhexidine on C. albicans in comparison with
      ketoconazole. Materials and Methods. Samples were collected using sterile cotton
      swabs, swabbed on the tooth surfaces from children with ECC of 3 to 6 yrs and
      streaked on Sabouraud dextrose agar (HI Media) plates and incubated in a 5% CO2
      enriched atmosphere at 37 degrees C for 24 hours. Candida was isolated and its
      susceptibility to probiotics, chlorhexidine, ketoconazole, and coconut oil was
      determined using Disc Diffusion method. Results. The mean zone of inhibition for
      chlorhexidine was 21.8 mm, whereas for coconut oil it was 16.8 mm, for probiotics
      it was 13.5 mm, and for ketoconazole it was 22.3 mm. The difference between the
      groups was not statistically significant (Chi-square value 7.42, P value 0.06).
      Conclusion. Chlorhexidine and coconut oil have shown significant antifungal
      activity which is comparable with ketoconazole. 

PMID- 27051560
TI  - Distribution of Heavy Metals in the Soils Associated with the Commonly Used
      Pesticides in Cotton Fields.
AB  - Agricultural soils contain both heavy metals and pesticides originating from
      various agricultural practices. It is quite important to study the relationships
      between these two classes of compounds. To accomplish this, 52 soil samples were
      collected from cotton fields and analyzed for their metal contents (Ni, Cu, Co,
      Pb, Cr, and Cd) and levels of most commonly used pesticides (imidacloprid,
      acetamiprid, and emamectin). FAAS was used for metal estimation and the
      pesticides were determined by HPLC equipped with UV detector. The results of the
      study revealed slightly enhanced levels of Ni and Cd in these samples while the
      rest of the metals were present within tolerable range. Acetamiprid residues in
      soil were strongly positively correlated with Cu and negatively correlated with
      Cr. Similarly, imidacloprid in soil was negatively correlated with Ni. Thus it
      was evidenced that Cu stabilizes acetamiprid while Cr and Ni facilitate the
      degradation of acetamiprid and imidacloprid in the soil. 

PMID- 27051562
TI  - The association between PGC-1alpha and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder and its reported
      pathophysiological features in the brain include the deposition of amyloid beta
      peptide, chronic inflammation, and cognitive impairment. The incidence of AD is
      increasing worldwide and researchers have studied various aspects of AD
      pathophysiology in order to improve our understanding of the disease. Thus far,
      the onset mechanisms and means of preventing AD are completely unknown.
      Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha) is a
      protein related to various cellular mechanisms that lead to the alteration of
      downstream gene regulation. It has been reported that PGC-1alpha could protect
      cells against oxidative stress and reduce mitochondrial dysfunction. Moreover, it
      has been demonstrated to have a regulatory role in inflammatory signaling and
      insulin sensitivity related to cognitive function. Here, we present further
      evidence of the involvement of PGC-1alpha in AD pathogenesis. Clarifying the
      relationship between PGC-1alpha and AD pathology might highlight PGC-1alpha as a
      possible target for therapeutic intervention in AD. 

PMID- 27051563
TI  - Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial
      hypertension rats after ranolazine treatment.
AB  - Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease
      characterized by sustained increase in the pulmonary arterial pressure and
      excessive thickening and remodeling of the distal small pulmonary arteries.
      During disease progression, structural remodeling of the right ventricular (RV)
      impairs pump function, creates pro-arrhythmic substrates and triggers for
      arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to
      cardiac death in PAH that are not directly addressed by currently available
      therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has
      cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic
      effects due to inhibition of the late sodium current in cardiomyocytes.
      Therefore, we hypothesized that RAN could reduce the mal-adaptive structural
      remodeling of the RV, and prevent triggered ventricular arrhythmias in the
      monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy,
      reduced levels of B-type natriuretic peptide, and decreased the expression of
      fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH.
      These results support the notion that RAN can improve the functional properties
      of the RV, highlighting its potential benefits in the setting of heart
      impairment. 

PMID- 27051561
TI  - Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach.
AB  - One of the extreme challenges in biology is to ameliorate the understanding of
      the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these
      pretend to have influence on human health. However, it has been manifested that
      MED could be either inherited as inborn error of metabolism (IEM) or acquired,
      which carries a high risk of interrupted biochemical reactions. Enzyme deficiency
      results in accumulation of toxic compounds that may disrupt normal organ
      functions and cause failure in producing crucial biological compounds and other
      intermediates. The MED related disorders cover widespread clinical presentations
      and can involve almost any organ system. To sum up the causal factors of almost
      all the MED-associated disorders, we decided to embark on a less traveled but
      nonetheless relevant direction, by focusing our attention on associated gene
      family products, regulation of their expression, genetic mutation, and mutation
      types. In addition, the review also outlines the clinical presentations as well
      as diagnostic and therapeutic approaches. 

PMID- 27051564
TI  - Correcting of pronated feet reduce skeletal muscle injury in young women with
      biomechanical abnormalities.
AB  - Biomechanical abnormalities of pronated feet accompanied by functional leg length
      disparity may increase the risk of skeletal muscle injury. Objective of the study
      is to prove that correction of pronated feet by the foot orthoses will reduce the
      creatine kinase-MM (CK-MM) concentrations as the muscle injury indicator. The
      design study was double blind randomized clinical trials with control. Research
      subjects were divided into two groups, group 1 used the foot orthoses while group
      2 did not used the foot orthoses. The whole subject examined the concentrations
      of the CK-MM enzyme before, and 24-72 hours after the walking test. The walking
      test was conducted 15 minutes with maximum speed. The concentration of the CK-MM
      enzyme before walking test on treatment group was 70.07+/-15.33 International
      Unit (IU), similar with the control group was 69.85+/-17.03 IU (P=0.971). The
      increased in CK-MM enzyme concentrations 45 hours after the walking test was
      lower in the treatment group (7.8+/-9 IU) than the control group (22.0+/-11.5 IU)
      (P=0.001). The CK-MM enzyme concentrations continued to decline in the treatment
      group after the second walking test (77.21+/-17.47 IU), and after the third
      walking test (69.86+/-11.88 IU) (P=0.018). The foot orthoses for correcting the
      pronated feet on the young women with biomechanical abnormalities is able to
      reduce the degree of the skeletal muscle injury after walking activity. 

PMID- 27051565
TI  - Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and
      no neuronal survival in parahippocampal cortices by long-term post-lesion
      melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy.
AB  - Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in
      melatonin treated lithium-pilocarpine epileptic rats during early and chronic
      phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction,
      5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals
      were killed 60 days post SE induction and the histological features of the rosrto
      caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were
      evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining.
      Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific
      pattern along the rostro-caudal axis of the dorsal hippocampus. The number of
      counted granular cells by melatonin (20 mg/kg) treatment increased along the
      rostro-caudal axis of the dorsal hippocampus in comparison to the untreated
      epileptic group. The density of Timm granules in the inner molecular layer of the
      dentate gyrus decreased significantly in all melatonin treated groups in
      comparison to the untreated epileptic animals. The increased density of synapsin
      I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated
      epileptic rats showed a profound decrease following melatonin treatment. There
      was no neuronal protection in the piriform and entorhinal cortices whatever the
      melatonin treatment. Long-term melatonin administration as a co-adjuvant probably
      could reduce the post-lesion histological consequences of TLE in a region
      specific pattern along the rostro-caudal axis of the dorsal hippocampus. 

PMID- 27051566
TI  - Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of
      rat offspring: postnatal follow-up study.
AB  - The direct interactive effects of rosemary and acrylamide on the development of
      motor neurons in the spinal cord remains unknown. Our goal is to confirm the
      protective effects of rosemary against motor neuronal degeneration induced by
      acrylamide in the developing postnatal rat spinal cord using a postnatal rat
      model. We assigned the offspring of treated female rats into control, rosemary;
      acrylamide group; and recovery groups. This work depended on clinical,
      histopathological, morphometrically, immunohistochemical and genetic methods. In
      the acrylamide group, we observed oxidation, motor neuron degeneration,
      apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis.
      Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these
      effects. These findings proof that dietary rosemary can directly protect motor
      neuron against acrylamide toxicity in the mammalian developing spinal cord.